PMID- 23947747
TI  - Seborrheic dermatitis: predisposing factors and ITS2 secondary structure for
      Malassezia phylogenic analysis.
AB  - Seborrheic dermatitis (SD) is a chronic, widespread skin condition, which is
      considered a multifactorial disease influenced, in part, by Malassezia spp.
      opportunistic activities, as well as various endogenous and exogenous factors.
      Malassezia species are lipophilic, lipid-dependent yeasts that are members of the
      normal mycobiota of the human skin. Their isolation from SD lesions varies around
      the world and the study of the relationship among factors such as gender, age,
      immunosuppressive condition of the patient and SD development, can lead to a
      better understanding of this disease. To elucidate the association of age and
      gender with the development of SD and to precisely determine the Malassezia
      species involved in the disease, samples were obtained from 134 individuals,
      including individuals without lesions, human immunodeficiency virus positive
      patients, individuals with seborrheic dermatitis, and HIV patients with
      seborrheic dermatitis. Malassezia spp. were identified by phenotypic and
      genotypic methods and a phylogenetic analysis was performed using Bayesian
      inference. This study revealed that age and gender are not predisposing factors
      for SD development, and that the most frequent species of Malassezia related to
      SD development among the Colombian population is M. restricta. We also report the
      isolation of M. yamatoensis for the first time in Colombia, and propose an ITS2
      secondary structure from Malassezia taxa that can be used for precise
      identification and to establish more robust phylogenetic relationships.

PMID- 23947748
TI  - Enhanced potentiometry by metallic nanoparticles.
AB  - Measuring the oxidation-reduction potential (Eh) requires an interface that is
      not selective toward specific species but exchanges electrons with all redox
      couples in the solution. Sluggish electron transfer (ET) kinetics with the
      species will not reflect the "true" Eh of the solution. Here, we present a novel
      approach by which adsorbed metal nanoparticles (NPs) are used for enhancing ET
      exchange rates between redox species and electrode surface and therefore affect
      significantly the measurement of the open circuit potential (OCP) and cyclic
      voltammetry (CV). The OCP and CV of various organic and inorganic species such as
      l-dopa, dopac, iron(II), and iodide are measured by bare stainless steel and by
      stainless steel modified by either Pt or Au NPs. We study the effect of the
      surface coverage of the stainless steel surface by NPs on the electrochemical
      response. Moreover, the stainless steel electrode was modified simultaneously by
      Au and Pt nanoparticles. This improved concurrently the stainless steel response
      (CV and potentiometry) toward two different species; l-dopa, which shows fast
      electron transfer on Pt, and catechol, which exhibits fast electron transfer on
      Au. We believe that this approach could be a first step toward developing a
      superior electrode for measuring the "true" Eh of complex aquatic systems. 

PMID- 23947749
TI  - Comorbidities in combined retinal artery and vein occlusions.
AB  - BACKGROUND: Several general diseases cause blindness in patients with
      simultaneous combined retinal artery and vein occlusion. METHODS/PATIENTS: We
      examined 14 patients with acute unilateral visual loss due to combined retinal
      artery and venous occlusions. All 14 patients presented at the Polyclinic over a
      period of about 3 years. Fluorescein angiography was carried out in 12 patients
      to confirm the diagnosis. Ten patients underwent Doppler sonography and 11
      echocardiography. RESULTS: Concerning systemic diseases, 11 of our 14 patients
      presented several cardiovascular risk factors, i.e., immunocytoma and arterial
      hypertension and hypercholesterolemia in one patient; another patient had chronic
      bronchitis, tachycardia and hypercholesterolemia. Six patients presented
      coagulation anomalies, and eight patients had arterial hypertension.Doppler
      sonography revealed normal carotid arteries in nine of ten patients. In 8 of 11
      patients, echocardiography displayed no cardiac abnormalities.Ophthalmoscopy
      revealed no emboli in any of these patients. CONCLUSION: Unilateral simultaneous
      combined incomplete retinal artery and venous occlusions should be considered as
      one entity. Eleven of our patients presented comorbidities reflecting several
      cardiovascular risk factors. Immunological diseases, malignancies and
      coagulopathies can cause this ocular disorder, resulting in blindness. No emboli
      were found in any of these patients. Patients suffering from acute visual loss
      must be examined for the presence of systemic diseases to enable therapy at an
      early stage.

PMID- 23947750
TI  - Unusual cryptosporidiosis cases in Swedish patients: extended molecular
      characterization of Cryptosporidium viatorum and Cryptosporidium chipmunk
      genotype I.
AB  - Most human cases of cryptosporidiosis are caused by Cryptosporidium parvum or
      Cryptosporidium hominis, but the use of molecular diagnostic methods has revealed
      that several other less common species or genotypes can also be involved. Here,
      we describe two unusual causes of cryptosporidiosis, one being the recently
      described species Cryptosporidium viatorum and the other Cryptosporidium chipmunk
      genotype I. Two Swedish patients who were infected with C. viatorum had travelled
      to Kenya and Guatemala, respectively, and two others had been infected with
      Cryptosporidium chipmunk genotype I in Sweden. None of these four patients were
      immunocompromised, and all four showed classical symptoms of cryptosporidiosis.
      We performed extensive molecular characterization, including analysis of four
      loci. The two C. viatorum isolates were found to differ slightly at the 70-kDa
      heat shock protein locus, which may indicate a local geographical variation in
      this species that has previously been described exclusively on the Indian
      subcontinent.

PMID- 23947751
TI  - Exome sequencing of a patient with suspected mitochondrial disease reveals a
      likely multigenic etiology.
AB  - BACKGROUND: The clinical features of mitochondrial disease are complex and highly
      variable, leading to challenges in establishing a specific diagnosis. Despite
      being one of the most commonly occurring inherited genetic diseases with an
      incidence of 1/5000, ~90% of these complex patients remain without a DNA-based
      diagnosis. We report our efforts to identify the pathogenetic cause for a patient
      with typical features of mitochondrial disease including infantile cataracts,
      CPEO, ptosis, progressive distal muscle weakness, and ataxia who carried a
      diagnosis of mitochondrial disease for over a decade. METHODS: Whole exome
      sequencing and bioinformatic analysis of these data were conducted on the
      proband. RESULTS: Exome sequencing studies showed a homozygous splice site
      mutation in SETX, which is known to cause Spinocerebellar Ataxia, Autosomal
      Recessive 1 (SCAR1). Additionally a missense mutation was identified in a highly
      conserved position of the OCRL gene, which causes Lowe Syndrome and Dent Disease
      2. CONCLUSIONS: This patient's complex phenotype reflects a complex genetic
      etiology in which no single gene explained the complete clinical presentation.
      These genetic studies reveal that this patient does not have mitochondrial
      disease but rather a genocopy caused by more than one mutant locus. This study
      demonstrates the benefit of exome sequencing in providing molecular diagnosis to
      individuals with complex clinical presentations.

PMID- 23947752
TI  - The myosin duty ratio tunes the calcium sensitivity and cooperative activation of
      the thin filament.
AB  - In striated muscle, calcium binding to the thin filament (TF) regulatory complex
      activates actin-myosin ATPase activity, and actin-myosin kinetics in turn
      regulates TF activation. However, a quantitative description of the effects of
      actin-myosin kinetics on the calcium sensitivity (pCa50) and cooperativity (nH)
      of TF activation is lacking. With the assumption that TF structural transitions
      and TF-myosin binding transitions are inextricably coupled, we advanced the
      principles established by Kad et al. [Kad, N., et al. (2005) Proc. Natl. Acad.
      Sci. U.S.A. 102, 16990-16995] and Sich et al. [Sich, N. M., et al. (2011) J.
      Biol. Chem. 285, 39150-39159] to develop a simple model of TF regulation, which
      predicts that pCa50 varies linearly with duty ratio and that nH is maximal near
      physiological duty ratios. Using in vitro motility to determine the calcium
      sensitivity of TF sliding velocities, we measured pCa50 and nH at different
      myosin densities and in the presence of ATPase inhibitors. The observed effects
      of myosin density and actin-myosin duty ratio on pCa50 and nH are consistent with
      our model predictions. In striated muscle, pCa50 must match cytosolic calcium
      concentrations and a maximal nH optimizes calcium responsiveness. Our results
      indicate that pCa50 and nH can be predictably tuned through TF-myosin ATPase
      kinetics and that drugs and disease states that alter ATPase kinetics can,
      through their effects on calcium sensitivity, alter the efficiency of muscle
      contraction. 

PMID- 23947753
TI  - Intrinsically stretchable supercapacitors composed of polypyrrole electrodes and
      highly stretchable gel electrolyte.
AB  - There has been an emerging interest in stretchable power sources compatible with
      flexible/wearable electronics. Such power sources must be able to withstand large
      mechanical strains and still maintain function. Here we report a highly
      stretchable H3PO4-poly(vinyl alcohol) (PVA) polymer electrolyte obtained by
      optimizing the polymer molecular weight and its weight ratio to H3PO4 in terms of
      conductivity and mechanical properties. The electrolyte demonstrates a high
      conductivity of 3.4 * 10(-3) S cm(-1), and a high fracture strain at 410%
      elongation. It is mechanically robust with a tensile strength of 2 MPa and a
      Young's modulus of 1 MPa, and displays a small plastic deformation (5%) after
      1000 stretching cycles at 100% strain. A stretchable supercapacitor device has
      been developed based on buckled polypyrrole electrodes and the polymer
      electrolyte. The device shows only a small capacitance loss of 5.6% at 30%
      strain, and can retain 81% of the initial capacitance after 1000 cycles of such
      stretching. 

PMID- 23947754
TI  - Development of new deoxycytidine kinase inhibitors and noninvasive in vivo
      evaluation using positron emission tomography.
AB  - Combined inhibition of ribonucleotide reductase and deoxycytidine kinase (dCK) in
      multiple cancer cell lines depletes deoxycytidine triphosphate pools leading to
      DNA replication stress, cell cycle arrest, and apoptosis. Evidence implicating
      dCK in cancer cell proliferation and survival stimulated our interest in
      developing small molecule dCK inhibitors. Following a high throughput screen of a
      diverse chemical library, a structure-activity relationship study was carried
      out. Positron Emission Tomography (PET) using (18)F-L-1-(2'-deoxy-2'
      FluoroArabinofuranosyl) Cytosine ((18)F-L-FAC), a dCK-specific substrate, was
      used to rapidly rank lead compounds based on their ability to inhibit dCK
      activity in vivo. Evaluation of a subset of the most potent compounds in cell
      culture (IC50 = ~1-12 nM) using the (18)F-L-FAC PET pharmacodynamic assay
      identified compounds demonstrating superior in vivo efficacy. 

PMID- 23947755
TI  - Mechanistic understanding of the effect of PPIs and acidic carbonated beverages
      on the oral absorption of itraconazole based on absorption modeling with
      appropriate in vitro data.
AB  - Proton pump inhibitors (PPIs) are potent gastric acid suppressing agents and are
      among the most widely sold drugs in the world. However, even though these
      antisecretory agents are regarded as safe, they can alter the pharmacokinetics of
      coadministered drugs. Due to the suppression of gastric acid secretion, they can
      significantly alter the intragastric pH conditions and are thus likely to affect
      the bioavailability of coadministered drugs requiring an acidic gastric
      environment for dissolution and subsequent absorption. Among these drugs can be
      found itraconazole, a poorly soluble triazole-type antifungal compound. Based on
      observations reported in the literature, gastric pH alterations due to the
      coadministration of PPIs or acidic beverages can significantly decrease (PPI) or
      increase (e.g., Coca-Cola) the bioavailability of this compound. In the present
      work we estimated the fraction of itraconazole that can be absorbed (fabs) from
      Sporanox capsules or an itraconazole-HBenBCD complex formulation after oral
      administration with and without coadministration of a PPI or an acidic
      (carbonated) beverage. For this purpose, the sensitivity of the two formulations
      toward the impact of various gastric variations (pH, volume, and emptying rate)
      as they can result from such administration conditions was studied using
      solubility and dissolution experiments and a physiologically based absorption
      model. Simulating coadministration of the two formulations with a PPI resulted in
      a significant (~ 10-fold) decrease in itraconazole fabs, indicating the pH to be
      essential for in vivo dissolution and subsequent absorption. The fabs of
      itraconazole after coadministration of an acidic beverage (Coca-Cola) was far
      lower than the fabs obtained for itraconazole alone and did not support the
      observations reported in the literature. These results clearly indicate that in
      contrast to PPIs, which seem to affect itraconazole bioavailability mainly via
      intragastric pH changes, coadministered Coca-Cola is likely to alter a range of
      gastrointestinal parameters relevant to in vivo dissolution rather than solely
      affecting the intragastric pH.

PMID- 23947756
TI  - Theoretical views on activation of methane catalyzed by Hf2+ and oxidation of CO
      (x(1)Sigma(+)) by N2O (x(1)Sigma(+)) Catalyzed by HfO2+ and TaO2+.
AB  - The mechanisms of activation of CH4 catalyzed by (1/3)Hf(2+) and oxidation of CO
      by N2O catalyzed by (1/3)HfO(2+) or (2/4)TaO(2+) have been investigated using the
      B3LYP level of theory. For the activation of methane, the TSR (two-state
      reactivity) mechanism has been certified through the spin-orbit coupling (SOC)
      calculation and the Landau-Zener-type model. In the vicinity of the minimum
      energy crossing point (MECP), SOC equals 900.23 cm(-1) and the probability of
      intersystem crossing is approximately 0.62. Spin inversion makes the activation
      barrier decline from 1.63 to 0.57 eV. NBO analysis demonstrates that empty 6s and
      5d orbitals of the Hf atom play the major role for the activation of C-H bonds.
      Finally, CH4 dehydrogenates to produce Hf-CH2(2+). For oxidation of CO by N2O
      catalyzed by HfO(2+) or TaO(2+), the covalent bonds between transition metal
      atoms and the oxygen atom restrict the freedom of valence electrons. Therefore,
      they are all SSR (single-state reactivity). The oxygen atom is directly extracted
      during the course of oxygen transfer, and its microscopic essence has been
      discussed. The detailed kinetic information of two catalytic cycles has been
      calculated by referencing the "energetic span (deltaE)" model. Finally,
      TOF(HfO(2+))/TOF(TaO(2+)) = 2.7 at 298.15 K, which has a good consistency with
      the experimental result. 

PMID- 23947757
TI  - Factors associated with recency of HIV testing amongst men residing in Scotland
      who have sex with men.
AB  - Rates of HIV testing are increasing among men who have sex with men (MSM) in
      Scotland and the UK. However, it remains vital to encourage MSM to test for HIV.
      The aim of the current study was to determine which factors discriminated among
      three groups of MSM: those tested for HIV within the previous year, those who had
      tested over one year previously, and those who had never tested. Cross-sectional
      data were collected using self-report, anonymous questionnaires from MSM
      frequenting gay venues in Glasgow, Scotland, during July 2010 (N = 822, response
      rate 62.6%). Those who identified themselves as HIV positive (n = 38), did not
      normally reside in Scotland (n = 88), and did not provide information on HIV
      testing (n = 13), were excluded (139 excluded, leaving N = 683). Around 57% (n =
      391) had tested for HIV within the previous year, 23% (n = 155) had tested over
      one year previously and 20% (n = 137) had never tested. Compared with those
      tested within the previous year, those tested over one year previously and those
      never tested had greater fear of a positive-HIV test result, a weaker norm for
      HIV testing, and were more likely to have had no anal sex partners at all within
      the previous year. Those tested over one year previously were significantly older
      than both other groups (who were more likely to be under 25 years of age).
      Unprotected anal intercourse (UAI) did not discriminate among the HIV testing
      groups. The results highlight the need to promote HIV testing in Scotland among
      those under 25 years and over 45 years, those with high fear of testing, and
      those whose sexual behaviour puts them at risk. Interventions to increase HIV
      testing should promote positive norms and challenge the fear of a positive
      result.

PMID- 23947758
TI  - Wechsler Adult Intelligence Scale-Third Edition profiles and their relationship
      to self-reported outcome following traumatic brain injury.
AB  - Neuropsychological assessments of outcome after traumatic brain injury (TBI) are
      often unrelated to self-reported problems after TBI. The current study cluster
      analyzed the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) subtest
      scores from mild, moderate, and severe TBI (n=220) and orthopedic injury control
      (n=95) groups, to determine whether specific cognitive profiles are related to
      people's perceived outcomes after TBI. A two-stage cluster analysis produced 4-
      and 6-cluster solutions, with the 6-cluster solution better capturing subtle
      variations in cognitive functioning. The 6 clusters differed in the levels and
      profiles of cognitive performance, self-reported recovery, and education and
      injury severity. The findings suggest that subtle cognitive impairments after TBI
      should be interpreted in conjunction with patient's self-reported problems.

PMID- 23947759
TI  - The influence of metabolic effects on stable hydrogen isotopes in tissues of
      aquatic organisms.
AB  - A steady-state mass-balance model describing controls on the stable hydrogen
      isotopic ratios (delta(2)H) of tissues in fish was previously developed but
      physiological effects related to fish size and growth had not been tested. Here,
      we assessed the influence of size (or growth rate) on tissue delta(2)H
      composition of a fish species (Poecilia reticulata) and the incorporation of
      metabolic products derived from dietary lipids (water, NADH). Sampled tissues
      were obtained from individuals that grew at different rates while raised on an
      isotopically homogeneous commercial diet (lipid-free fraction, delta(2)H=-95+/-2
      0/00; and dietary lipids,-198+/-11 0/00) under different controlled water
      hydrogen isotopic composition (delta(2)H=-128+/-3 0/00;+17+/-5 0/00; and+202+/-5
      0/00). Our findings suggested that fish growth rate was correlated positively
      with the degree of incorporation of metabolic products from dietary lipids that,
      in turn, influenced both fish tissue protein and lipid delta(2)H values. We
      conclude that delta(2)H measurements of lipids (and, subsequently, of body water)
      in fish could become a physiological tool that provides insights into fish growth
      rates.

PMID- 23947760
TI  - Myofascial trigger points, pain, disability, and sleep quality in patients with
      chronic nonspecific low back pain.
AB  - OBJECTIVE: To investigate the difference in the presence of trigger points (TrPs)
      between patients with chronic nonspecific low back pain (LBP) and healthy people,
      and to determine the relationship of TrPs with the intensity of ongoing pain,
      disability, and sleep quality. DESIGN: A cross-sectional study. SETTING: The role
      of TrPs in LBP has not been determined. PATIENTS: Forty-two patients with
      nonspecific LBP (50% women), aged 23-55 years old, and 42 age- and sex-matched
      controls participated. OUTCOME MEASURES: TrPs were bilaterally explored within
      the quadratus lumborum, iliocostalis lumborum, psoas, piriformis, gluteus
      minimus, and gluteus medius muscles in a blinded design. TrPs were considered
      active if the subject recognized the local and referred pain as familiar
      symptoms, and TrPs were considered latent if the pain was not recognized as a
      familiar symptom. Pain measures were collected with a numerical pain rate scale,
      disability was assessed with the Roland-Morris questionnaire, and sleep quality
      was determined with the Pittsburgh Sleep Quality Index. RESULTS: Patients with
      nonspecific LBP exhibited a greater disability and worse sleep quality than
      healthy controls (P < 0.001). Patients with nonspecific LBP exhibited a mean of
      3.5 +/- 2.3 active TrPs. Further, patients with nonspecific LBP showed a greater
      (P < 0.001) number of latent TrPs (mean: 2.0 +/- 1.5) than healthy controls
      (mean: 1.0 +/- 1.5). Active TrPs in the quadratus lumborum, iliocostalis
      lumborum, and gluteus medius muscles were the most prevalent in patients with
      nonspecific LBP. A greater number of active TrPs was associated with higher pain
      intensity (rs  = 0.602; P < 0.001) and worse sleep quality (rs  = 0.338; P =
      0.03). CONCLUSIONS: The local and referred pain elicited by active TrPs in the
      back and hip muscles contributes to pain symptoms in nonspecific LBP. Patients
      had higher disability and worse sleep quality than controls. The number of active
      TrPs was associated with pain intensity and sleep quality. It is possible that a
      complex interaction among these factors is present in patients with nonspecific
      LBP.

PMID- 23947761
TI  - Copper-catalyzed tandem azide-alkyne cycloaddition, Ullmann type C-N coupling,
      and intramolecular direct arylation.
AB  - A ligand-free copper-catalyzed tandem azide-alkyne cycloaddition (CuAAC), Ullmann
      type C-N coupling, and intramolecular direct arylation has been described. The
      designed strategy resulted in the synthesis of a novel trazole-fused
      azaheterocycle framework. The reaction gave good yields (59-77%) of 1,2,3
      triazole-fused imidazo[1,2-a]pyridines in a single step. 

PMID- 23947762
TI  - Control of Taenia solium taeniasis/cysticercosis: past practices and new
      possibilities.
AB  - Neurocysticercosis continues to be a major health burden on humans living in many
      regions of the world, despite the availability of highly effective taeniacides
      and identification of the cause, Taenia solium, as being potentially eradicable.
      Several T. solium control trials have been undertaken, generally achieving
      limited success and none that has been fully documented has achieved what was
      demonstrated to be a sustainable level of disease control. Pigs act as
      intermediate hosts for T. solium and two new control tools have become available
      for application in pigs - single-dose oxfendazole treatment of porcine
      cysticercosis and the TSOL18 vaccine. Three potential intervention scenarios for
      pigs are compared for control of cysticercosis, using either oxfendazole or
      vaccination. A control scenario involving vaccination plus oxfendazole treatment
      delivered at 4 monthly intervals was predicted to achieve the best outcome, with
      no pigs slaughtered at 12 months of age having viable T. solium cysticerci. Now
      that new control tools are available, there are opportunities to concentrate
      research attention on evaluation of novel control scenarios leading to the
      implementation of effective and sustainable control programmes and a reduction in
      the global burden of neurocysticercosis.

PMID- 23947763
TI  - Establishing the ground state of the disjoint diradical tetramethyleneethane with
      quantum Monte Carlo.
AB  - The nature of the electronic ground state of the tetramethyleneethane (TME)
      diradical has proven to be a challenge for both experiment and theory. Through
      the use of quantum Monte Carlo (QMC) methods and multireference perturbation
      theory, we demonstrate that the lowest singlet state of TME is energetically
      lower than the lowest triplet state at all values of the torsional angle between
      the allyl subunits. Moreover, we find that the maximum in the potential energy
      curve for the singlet state occurs at a torsional angle near 45 degrees , in
      contrast to previous calculations that placed the planar structure of the singlet
      state as the highest in energy. We also show that the CASPT2 method when used
      with a sufficiently large reference space and a sufficiently flexible basis set
      gives potential energy curves very close to those from the QMC calculations. Our
      calculations have converged the singlet-triplet gap of TME as a function of
      methodology and basis set. These results provide insight into the level of theory
      required to properly model diradicals, in particular disjoint diradicals, and
      provide guidelines for future studies on more complicated diradical systems. 

PMID- 23947764
TI  - Changes in feed intake, nutrient digestion, plasma metabolites, and oxidative
      stress parameters in dairy cows with subacute ruminal acidosis and its regulation
      with pelleted beet pulp.
AB  - The objectives of this study were to 1) determine the variation of nutrient
      digestion, plasma metabolites and oxidative stress parameters triggered by
      induced subacute ruminal acidosis (SARA); and 2) evaluate the ability of pelleted
      beet pulp (BP) as a replacement for ground corn to alleviate SARA. Eight Holstein
      Friesian cows were fed four diets during four successive17-day periods: 1) total
      mixed ration (TMR) containing 0% finely ground wheat (FGW) (W0); 2) TMR
      containing 10% FGW (W10); 3) TMR containing 20% FGW (W20); and 4) TMR containing
      10% BP as a replacement for 10% ground corn (BP10). The SARA induction protocol
      reduced the mean ruminal pH from 6.37 to 5.94, and the minimum ruminal pH
      decreased from 5.99 to 5.41 from baseline to challenge period. Mean ruminal pH
      increased from 5.94 to 6.05, and minimum daily ruminal pH increased from 5.41 to
      5.63, when BP was substituted for corn. The apparent digestibility of nutrients
      was not affected by the dietary treatments, except that the digestibility of
      neutral detergent fibre (NDF) and acid detergent fibre (ADF) was reduced in cows
      fed the W20 diet compared with cows fed the W0 and W10 diets, and cows fed the
      BP10 diet had higher NDF and ADF digestibility than the cows fed the W20 diet.
      Cows fed the W20 diet had a lower plasma concentration of beta-hydroxybutyrate
      (BHBA), non-esterified fatty acids (NEFA), cholesterol, triglyceride, and total
      antioxidative capacity (TAC), and a higher plasma concentration of glucose,
      insulin, malonaldehyde (MDA), super oxygen dehydrogenises (SOD), and glutathione
      peroxidase (GSH-Px) than cows fed the W0 diet. Substitution of BP for corn
      increased concentrations of plasma BHBA and TAC, but decreased concentrations of
      plasma MDA. Our results indicate that reduction of fibre digestion; the
      concomitant increase of plasma glucose and insulin; the decrease of plasma BHBA,
      NEFA, cholesterol, and triglyceride; and changes of plasma oxidative stress
      parameters are highly related to SARA induced by W20 diets. These variables may
      be alternative candidates for SARA diagnosis. We also suggest that the
      substitution of BP for corn could reduce the risk of SARA, increase fibre
      digestion, and improve the antioxidant status in dairy cows. 

PMID- 23947765
TI  - Non-small cell lung cancer cells survived ionizing radiation treatment display
      cancer stem cell and epithelial-mesenchymal transition phenotypes.
AB  - Ionizing radiation (IR) is used for patients diagnosed with unresectable non
      small cell lung cancer (NSCLC), however radiotherapy remains largely palliative
      due to radioresistance. Cancer stem cells (CSCs), as well as epithelial
      mesenchymal transition (EMT), may contribute to drug and radiation resistance
      mechanisms in solid tumors. Here we investigated the molecular phenotype of A549
      and H460 NSCLC cells that survived treatment with IR (5Gy) and are growing as
      floating tumor spheres and cells that are maintained in a monolayer after
      irradiation.Non-irradiated and irradiated cells were collected after one week,
      seeded onto ultra low attachment plates and propagated as tumor spheres. Bulk
      NSCLC cells which survived radiation and grew in spheres express cancer stem cell
      surface and embryonic stem cell markers and are able to self-renew, and generate
      differentiated progeny. These cells also have a mesenchymal phenotype.
      Particularly, the radiation survived sphere cells express significantly higher
      levels of CSC markers (CD24 and CD44), nuclear beta-catenin and EMT markers
      (Snail1, Vimentin, and N-cadherin) than non-irradiated lung tumor sphere cells.
      Upregulated levels of Oct-4, Sox2 and beta-catenin were detected in H460 cells
      maintained in a monolayer after irradiation, but not in radiation survived
      adherent A459 cells.PDGFR-beta was upregulated in radiation survived sphere cells
      and in radiation survived adherent cells in both A549 and H460 cell lines.
      Combining IR treatment with axitinib or dasatinib, inhibitors with anti-PDFGR
      activity, potentiates the efficacy of NSCLC radiotherapy in vitro.Our findings
      suggest that radiation survived cells have a complex phenotype combining the
      properties of CSCs and EMT. CD44, SNAIL and PDGFR-beta are dramatically
      upregulated in radiation survived cells and might be considered as markers of
      radiotherapy response in NSCLC. 

PMID- 23947766
TI  - Brain proteomics supports the role of glutamate metabolism and suggests other
      metabolic alterations in protein l-isoaspartyl methyltransferase (PIMT)-knockout
      mice.
AB  - Protein l-isoaspartyl methyltransferase (PIMT) repairs the isoaspartyl residues
      (isoAsp) that originate from asparagine deamidation and aspartic acid (Asp)
      isomerization to Asp residues. Deletion of the gene encoding PIMT in mice (Pcmt1)
      leads to isoAsp accumulation in all tissues measured, especially in the brain.
      These PIMT-knockout (PIMT-KO) mice have perturbed glutamate metabolism and die
      prematurely of epileptic seizures. To elucidate the role of PIMT further, brain
      proteomes of PIMT-KO mice and controls were analyzed. The isoAsp levels from two
      of the detected 67 isoAsp sites (residue 98 from calmodulin and 68 from
      glyceraldehyde-3-phosphate dehydrogenase) were quantified and found to be
      significantly increased in PIMT-KO mice (p < 0.01). Additionally, the abundance
      of at least 151 out of the 1017 quantified proteins was found to be altered in
      PIMT-KO mouse brains. Gene ontology analysis revealed that many down-regulated
      proteins are involved in cellular amino acid biosynthesis. For example, the
      serine synthesis pathway was suppressed, possibly leading to reduced serine
      production in PIMT-KO mice. Additionally, the abundances of enzymes in the
      glutamate-glutamine cycle were altered toward the accumulation of glutamate.
      These findings support the involvement of PIMT in glutamate metabolism and
      suggest that the absence of PIMT also affects other processes involving amino
      acid synthesis and metabolism. 

PMID- 23947767
TI  - Interaction of profilin with the barbed end of actin filaments.
AB  - Profilin binds not only to actin monomers but also to the barbed end of the actin
      filament, where it inhibits association of subunits. To address open questions
      about the interactions of profilin with barbed ends, we measured the effects of a
      wide range of concentrations of Homo sapiens profilin 1 on the rate of elongation
      of individual skeletal muscle actin filaments by total internal reflection
      fluorescence microscopy. Much higher concentrations of profilin were required to
      stop elongation by AMP-PNP-actin monomers than ADP-actin monomers. High
      concentrations of profilin depolymerized barbed ends at a rate much faster than
      the spontaneous dissociation rates of Mg-ATP-, Mg-AMP-PNP-, Mg-ADP-Pi-, and Mg
      ADP-actin subunits. Fitting a thermodynamic model to these data allowed us to
      determine the affinities of profilin and profilin-actin for barbed ends and the
      influence of the nucleotide bound to actin on these interactions. Profilin has a
      much higher affinity for ADP-actin filament barbed ends (Kd = 1 MUM) than AMP-PNP
      actin filament barbed ends (Kd = 226 MUM). ADP-actin monomers associated with
      profilin bind to ADP-actin filament barbed ends 10% as fast as free ADP-actin
      monomers, but bound profilin does not affect the rate of association of AMP-PNP
      actin monomers with barbed ends. The differences in the affinities of AMP-PNP-
      and ADP-bound barbed ends for profilin and profilin-actin suggest that
      conformations of barbed end subunits differ from those of monomers and change
      upon nucleotide hydrolysis and phosphate release. A structural model revealed
      minor steric clashes between profilin and actin subunits at the barbed end that
      explain the biochemical results. 

PMID- 23947768
TI  - Graphene/Fe2O3/SnO2 ternary nanocomposites as a high-performance anode for
      lithium ion batteries.
AB  - We report an rGO/Fe2O3/SnO2 ternary nanocomposite synthesized via homogeneous
      precipitation of Fe2O3 nanoparticles onto graphene oxide (GO) followed by
      reduction of GO with SnCl2. The reduction mechanism of GO with SnCl2 and the
      effects of reduction temperature and time were examined. Accompanying the
      reduction of GO, particles of SnO2 were deposited on the GO surface. In the
      graphene nanocomposite, Fe2O3 nanoparticles with a size of ~20 nm were uniformly
      dispersed surrounded by SnO2 nanoparticles, as demonstrated by transmission
      electron microscopy analysis. Due to the different lithium insertion/extraction
      potentials, the major role of SnO2 nanoparticles is to prevent aggregation of
      Fe2O3 during the cycling. Graphene can serve as a matrix for Li+ and electron
      transport and is capable of relieving the stress that would otherwise accumulate
      in the Fe2O3 nanoparticles during Li uptake/release. In turn, the dispersion of
      nanoparticles on graphene can mitigate the restacking of graphene sheets. As a
      result, the electrochemical performance of rGO/Fe2O3/SnO2 ternary nanocomposite
      as an anode in Li ion batteries is significantly improved, showing high initial
      discharge and charge capacities of 1179 and 746 mAhg(-1), respectively.
      Importantly, nearly 100% discharge-charge efficiency is maintained during the
      subsequent 100 cycles with a specific capacity above 700 mAhg(-1).

PMID- 23947769
TI  - Tissue plasminogen activator (tPA) for ischemic stroke in patients aged >=80
      years.

PMID- 23947770
TI  - Response to letter to the editor; ANE-O-03-12-096.

PMID- 23947771
TI  - Differences in risk of malignancy and management recommendations in subcategories
      of thyroid nodules with atypia of undetermined significance or follicular lesion
      of undetermined significance: the role of ultrasound-guided core-needle biopsy.
AB  - BACKGROUND: The cytopathologic description of atypia of undetermined significance
      (AUS)/follicular lesion of undetermined significance (FLUS) includes nine
      different criteria in The Bethesda System, and the risk of malignancy in this
      category shows a wide range. The objectives of the present study were to
      determine whether ultrasound (US)-guided core-needle biopsy (CNB) indicates a
      different malignant risk, and to identify management recommendations, malignant
      US findings, and distribution of CNB readings in subcategories of AUS/FLUS
      category, as seen on previous thyroid fine-needle aspiration readings. METHODS:
      From October 2008 to July 2011, 191 thyroid nodules of 191 patients who had
      previously been diagnosed with nuclear atypia (Group AUS; n=84) and
      microfollicular architecture (Group FLUS; n=107) were enrolled in our
      retrospective study. Final diagnoses were obtained in 142 nodules after surgery
      and clinico-radiological follow-up. We compared the malignancy risk, management
      recommendation, malignant US findings, and distribution of CNB readings between
      the two groups and calculated the diagnostic value of CNB. RESULTS: With CNB, the
      final malignancy results were greater in Group AUS (65%, 33/51) than Group FLUS
      (14.3%, 13/91; p<0.001), and there were more surgical candidates in Group AUS
      (57.8%, 46/84) than Group FLUS (19.6%, 21/107; p<0.001). CNB showed 95.8%
      diagnostic accuracy for identifying malignancies and 19.4% inconclusive readings.
      Malignant US findings were seen more frequently in Group AUS (76.5%, 39/51) than
      Group FLUS (52.7%, 48/91; p=0.007). Malignant CNB readings were statistically
      more frequent in Group AUS (49.2%, 41/84) than Group FLUS (9.4%, 10/107;
      p<0.001), and benign readings were statistically more frequent in Group FLUS
      (58.9%, 63/107) than Group AUS (28.6%, 24/84; p<0.001). CONCLUSIONS: US-guided
      CNB demonstrated that Group AUS showed a higher risk of malignancy, of becoming
      surgical candidates, of having malignant US findings, and of having malignant CNB
      readings than Group FLUS. Further management guidelines for Group AUS should
      differ from Group FLUS.

PMID- 23947772
TI  - The correlates of urinary albumin to creatinine ratio (ACR) in a high risk
      Australian aboriginal community.
AB  - BACKGROUND: Albuminuria marks renal disease and cardiovascular risk. It was
      estimated to contribute 75% of the risk of all-cause natural death in one
      Aboriginal group. The urine albumin/creatinine ratio (ACR) is commonly used as an
      index of albuminuria. This study aims to examine the associations between
      demographic factors, anthropometric index, blood pressure, lipid-protein
      measurements and other biomarkers and albuminuria in a cross-sectional study in a
      high-risk Australian Aboriginal population. The models will be evaluated for
      albuminuria at or above the microalbuminuria threshold, and at or above the
      "overt albuminuria" threshold with the potential to distinguish associations they
      have in common and those that differ. METHODS: This was a cross-sectional study
      of 598 adults aged 18-76 years. All participants were grouped into quartiles by
      age. Logistic regression models were used to explore the correlates of ACR
      categories. RESULTS: The significant correlates were systolic blood pressure
      (SBP), C-reactive protein (CRP), uric acid, diabetes, gamma-glutamyl transferase
      (GGT) (marginally significant, p=0.054) and serum albumin (negative association)
      for ACR 17+ (mg/g) for men and 25+ for women. Independent correlates were SBP,
      uric acid, diabetes, total cholesterol, alanine amino transferase (ALT), Cystatin
      C and serum albumin (negative association) for overt albuminuria; and SBP, CRP
      and serum albumin only for microalbuminuria. CONCLUSIONS: This is the most
      detailed modelling of pathologic albuminuria in this setting to date. The
      somewhat variable association with risk factors suggests that microalbuminuria
      and overt albuminuria might reflect different as well as shared phenomena.

PMID- 23947773
TI  - Dihydrothiazolopyridone derivatives as a novel family of positive allosteric
      modulators of the metabotropic glutamate 5 (mGlu5) receptor.
AB  - Starting from a singleton chromanone high throughput screening (HTS) hit, we
      describe a focused medicinal chemistry optimization effort leading to the
      identification of a novel series of phenoxymethyl-dihydrothiazolopyridone
      derivatives as selective positive allosteric modulators (PAMs) of the
      metabotropic glutamate 5 (mGlu5) receptor. These dihydrothiazolopyridones
      potentiate receptor responses in recombinant systems. In vitro and in vivo drug
      metabolism and pharmacokinetic (DMPK) evaluation allowed us to select compound
      16a for its assessment in a preclinical animal screen of possible antipsychotic
      activity. 16a was able to reverse amphetamine-induced hyperlocomotion in rats in
      a dose-dependent manner without showing any significant motor impairment or overt
      neurological side effects at comparable doses. Evolution of our medicinal
      chemistry program, structure activity, and properties relationships (SAR and SPR)
      analysis as well as a detailed profile for optimized mGlu5 receptor PAM 16a are
      described. 

PMID- 23947774
TI  - Study to assess the effect of a structured communication approach on quality of
      life in secure mental health settings (Comquol): study protocol for a pilot
      cluster randomized trial.
AB  - BACKGROUND: Forensic mental health services have largely ignored examining
      patients' views on the nature of the services offered to them. A structured
      communication approach (DIALOG) has been developed with the aim of placing the
      patient's perspective on their care at the heart of the discussions between
      patients and clinicians. The effectiveness of the structured communication
      approach in community mental health services has been demonstrated, but no trial
      has taken place in a secure psychiatric setting. This pilot study is evaluating a
      6-month intervention combining DIALOG with principles of solution-focused therapy
      on quality of life in medium-secure settings. METHODS AND DESIGN: A cluster
      randomized controlled trial design is being employed to conduct a 36-month pilot
      study. Participants are recruited from six medium-secure inpatient services, with
      48 patients in the intervention group and 48 in the control group. The
      intervention uses a structured communication approach. It comprises six meetings
      between patient and nurse held monthly over a 6-month period. During each
      meeting, patients rate their satisfaction with a range of life and treatment
      domains with responses displayed on a tablet. The rating is followed by a
      discussion of how to improve the current situation in those domains identified by
      the patient. Assessments take place prior to the intervention (baseline), at 6
      months (postintervention) and at 12 months (follow-up). The primary outcome is
      the patient's self-reported quality of life. DISCUSSION: This study aims to (1)
      establish the feasibility of the trial design as the basis for determining the
      viability of a large full-scale trial, (2) determine the variability of the
      outcomes of interest (quality of life, levels of satisfaction, disturbance, ward
      climate and engagement with services), (3) estimate the costs of the intervention
      and (4) refine the intervention following the outcome of the study based upon the
      experiences of the nurses and patients. The intervention allows patients to have
      a greater say in how they are treated and targets care in areas that patients
      identify as important to them. It is intended to establish systems that support
      meaningful patient and caregiver involvement and participation. TRIAL
      REGISTRATION: Current Controlled Trials, ISRCTN34145189.

PMID- 23947775
TI  - Symptoms, signs and nerve conduction velocities in patients with suspected carpal
      tunnel syndrome.
AB  - BACKGROUND: To inform the clinical management of patients with suspected carpal
      tunnel syndrome (CTS) and case definition for CTS in epidemiological research, we
      explored the relation of symptoms and signs to sensory nerve conduction (SNC)
      measurements. METHODS: Patients aged 20-64 years who were referred to a
      neurophysiology service for investigation of suspected CTS, completed a symptom
      questionnaire (including hand diagrams) and physical examination (including
      Tinel's and Phalen's tests). Differences in SNC velocity between the little and
      index finger were compared according to the anatomical distribution of symptoms
      in the hand and findings on physical examination. RESULTS: Analysis was based on
      1806 hands in 908 patients (response rate 73%). In hands with numbness or
      tingling but negative on both Tinel's and Phalen's tests, the mean difference in
      SNC velocities was no higher than in hands with no numbness or tingling. The
      largest differences in SNC velocities occurred in hands with extensive numbness
      or tingling in the median nerve sensory distribution and both Tinel's and
      Phalen's tests positive (mean 13.8, 95% confidence interval (CI) 12.6-15.0 m/s).
      Hand pain and thumb weakness were unrelated to SNC velocity. CONCLUSIONS: Our
      findings suggest that in the absence of other objective evidence of median nerve
      dysfunction, there is little value in referring patients of working age with
      suspected CTS for nerve conduction studies if they are negative on both Tinel's
      and Phalen's tests. Alternative case definitions for CTS in epidemiological
      research are proposed according to the extent of diagnostic information available
      and the relative importance of sensitivity and specificity.

PMID- 23947776
TI  - Contextualizing nativity status, Latino social ties, and ethnic enclaves: an
      examination of the 'immigrant social ties hypothesis'.
AB  - OBJECTIVES: Researchers have posited that one potential explanation for the
      better-than-expected health outcomes observed among some Latino immigrants, vis-a
      vis their US-born counterparts, may be the strength of social ties and social
      support among immigrants. METHODS: We examined the association between nativity
      status and social ties using data from the Chicago Community Adult Health Study's
      Latino subsample, which includes Mexicans, Puerto Ricans, and other Latinos.
      First, we used ordinary least squares (OLS) regression methods to model the
      effect of nativity status on five outcomes: informal social integration; social
      network diversity; network size; instrumental support; and informational support.
      Using multilevel mixed-effects regression models, we estimated the association
      between Latino/immigrant neighborhood composition and our outcomes, and whether
      these relationships varied by nativity status. Lastly, we examined the
      relationship between social ties and immigrants' length of time in the USA.
      RESULTS: After controlling for individual-level characteristics, immigrant
      Latinos had significantly lower levels of social ties than their US-born
      counterparts for all the outcomes, except informational support. Latino/immigrant
      neighborhood composition was positively associated with being socially integrated
      and having larger and more diverse social networks. The associations between two
      of our outcomes (informal social integration and network size) and living in a
      neighborhood with greater concentrations of Latinos and immigrants were stronger
      for US-born Latinos than for immigrant Latinos. US-born Latinos maintained a
      significant social ties advantage over immigrants - regardless of length of time
      in the USA - for informal social integration, network diversity, and network
      size. CONCLUSION: At the individual level, our findings challenge the assumption
      that Latino immigrants would have larger networks and/or higher levels of support
      and social integration than their US-born counterparts. Our study underscores the
      importance of understanding the contexts that promote the development of social
      ties. We discuss the implications of these findings for understanding Latino and
      immigrant social ties and health outcomes.

PMID- 23947777
TI  - Novel lipid hybrid albumin nanoparticle greatly lowered toxicity of pirarubicin.
AB  - Pirarubicin (THP) is an effective anthracycline for the treatment of solid tumor.
      However, its potential side effects are prominent and clinical use is restricted.
      We aimed to develop a novel pirarubicin-oleic acid complex albumin nanoparticle
      (THP-OA-AN) in order to reduce the toxicity of THP. Oleic acid, human serum
      albumin (HSA), and egg yolk lecithin E80 was used to prepare THP-OA-AN. Prepared
      THP-OA-AN was characterized and animal experiments were conducted to assess its
      tumor suppression effect, distribution, and toxicity. Comparison between THP and
      THP-OA-AN showed that, with retained antitumor efficiency, the toxicity of THP-OA
      AN is significantly reduced regarding bone marrow suppression, cardiotoxicity,
      renal toxicity, and gastrointestinal toxicity. This study developed a safe and
      effective formulation of THP, which has greater potential for clinic use in the
      tumor therapy. 

PMID- 23947778
TI  - Gonadal steroids regulate the expression of aggrecanases in human endometrial
      stromal cells in vitro.
AB  - The human endometrium undergoes cyclic change during each menstrual cycle in
      response to gonadal steroids. Proteolysis of endometrial extracellular matrix
      (ECM) is necessary to prepare this dynamic tissue for pregnancy. Proteolytic
      enzymes such as matrix metalloproteinase (MMP) and closely related a disintegrin
      and metalloproteinase with thrombospondin motifs (ADAMTS) have been assigned key
      roles in the highly regulated cyclic remodelling of the endometrial ECM. We have
      previously shown that ADAMTS-1 undergoes spatiotemporal changes in human
      endometrial stromal cells under the regulation of gonadal steroids. This suggests
      that other ADAMTS subtypes, known as aggrecanases, may contribute to the ECM
      remodelling events that occur in female physiological cycles and in preparation
      for pregnancy. To determine whether progesterone (P4), 17beta-estradiol (E2), or
      dihydrotestosterone (DHT), alone or in combination, are capable of regulating
      ADAMTS-4, -5, -8 or -9 expression in human endometrial stromal cells in vitro.
      Real-time quantitative PCR and Western blot analysis were used to measure ADAMTSs
      mRNA and protein levels in primary cultures of human endometrial stromal cells (n
      = 12). P4, DHT but not E2 have regulatory effects on ADAMTS-8, -9 and -5
      expression. Combined treatment with gonadal steroids did not show any synergistic
      or antagonistic effects. However, the synthetic steroid antagonists RU486 and
      hydroxyflutamide specifically inhibited the P4- or DHT-mediated regulatory
      effects on ADAMTS expression. These studies provide evidence that the regulation
      of aggrecanases by gonadal steroids in human endometrial stromal cells may play
      an important role during decidualization. 

PMID- 23947779
TI  - Carbon and electron fluxes during the electricity driven 1,3-propanediol
      biosynthesis from glycerol.
AB  - 1,3-Propanediol (1,3-PDO) can be produced biologically through glycerol
      fermentation. While such a process typically involves a pure culture system,
      particularly for crude glycerol, there would be operational advantages if a mixed
      population could be used. However, in the latter case the yield is typically low.
      Here, we use electrical current as the driving force for a mixed population
      fermenting glycerol in the cathode of a microbial bioelectrochemical system
      (BES). The carbon and electron flows were monitored by a titration and off-gas
      analysis (TOGA) sensor, and the syntrophic interactions in the BES were also
      investigated. Results show that on a carbon yield basis, current enhanced 1,3-PDO
      production from 24.8% (without current) to 50.1% (with a polarized biocathode at 
      0.9 V versus standard hydrogen electrode, SHE). Flux analysis indicated that the
      reductive current can be integrated into glycerol metabolism to enhance 1,3-PDO
      yield and that glycerol metabolism was redirected from propionate fermentation to
      1,3-PDO production. A polarization of -0.6 V (vs SHE) resulted in more
      fermentative hydrogen production (from 2.7% to 8.0% on electron basis). 1,3-PDO
      production was also enhanced with hydrogen supply (37.7% on carbon basis), by
      suppressing hydrogen fermentation. Moreover, interspecies hydrogen transfer
      encouraged hydrogenotrophic methanogenesis, which was also accelerated by the
      cathodic polarization. 

PMID- 23947780
TI  - Accurate determination of barrier height and kinetics for the F + H2O -> HF + OH
      reaction.
AB  - The reaction energy and barrier height of the title reaction are investigated
      using two high-level ab initio protocols, namely Focal Point Analysis (FPA) and
      modified High Accuracy Extrapolated Ab Initio Thermochemistry (HEAT) methods. It
      is concluded from these calculations that despite some multireference character,
      dynamic electron correlation plays a dominant role near the reaction barrier.
      Thus, the coupled-cluster method with higher excitations than singles and doubles
      gives a better description than the multireference configuration interaction
      method for the barrier height. The FPA and HEAT classical barrier heights,
      including the spin-orbit and other corrections, are 1.919 and 2.007 kcal/mol,
      respectively. The rate constants and H/D kinetic isotope effect for the title
      reaction are determined by semiclassical transition-state theory based on the
      anharmonic potential energy surface near the saddle point, and the agreement with
      experiment is excellent. The rate constants are also computed using a quasi
      classical trajectory method on a global potential energy surface scaled to the
      FPA barrier height and a similar level of agreement with experimental data is
      obtained. 

PMID- 23947781
TI  - Sorafenib for hepatocellular carcinoma before liver transplantation.

PMID- 23947782
TI  - Computerized measures of finger tapping: reliability, malingering and traumatic
      brain injury.
AB  - We analyzed computerized finger tapping metrics in four experiments. Experiment 1
      showed tapping-rate differences associated with hand dominance, digits, sex, and
      fatigue that replicated those seen in a previous, large-scale community sample.
      Experiment 2 revealed test-retest correlations (r = .91) that exceeded those
      reported in previous tapping studies. Experiment 3 investigated subjects
      simulating symptoms of traumatic brain injury (TBI); 62% of malingering subjects
      produced abnormally slow tapping rates. A tapping-rate malingering index, based
      on rate-independent tapping patterns, provided confirmatory evidence of
      malingering in 48% of the subjects with abnormal tapping rates. Experiment 4
      compared tapping in 24 patients with mild TBI (mTBI) and a matched control group;
      mTBI patients showed slowed tapping without evidence of malingering. Computerized
      finger tapping measures are reliable measures of motor speed, useful in detecting
      subjects performing with suboptimal effort, and are sensitive to motor
      abnormalities following mTBI. 

PMID- 23947783
TI  - 'Drinking is our modern way of bonding': young people's beliefs about
      interventions to encourage moderate drinking.
AB  - Efforts to discourage excessive alcohol use among young people can only be
      effective if the target audience is exposed to, attends to, and comprehends key
      messages. The aim of this study was to examine age and sex differences in
      drinking motives to better inform development of targeted interventions to reduce
      alcohol-related harm. Thirty individual interviews and 12 group interviews were
      conducted with English 13-25 year olds. Interviewees gave multiple motivations
      for drinking - especially those related to image and reputation, and played down
      the health implications of heavy drinking. Negative aspects of drinking - caring
      for drunk friends, being cared for when drunk and suffering through hangovers
      with friends - were considered to offer opportunities for closer interpersonal
      bonding than other social activities. Respondents distanced themselves from
      'problem' drinkers, but disapproved of others' problematic drinking or antisocial
      behaviour. Narrative messages demonstrating the social consequences of excessive
      consumption were preferred to single, static messages emphasising risk or harm.
      Interviewees noted that interventions must use an engaging tone or pitch: they
      considered many campaigns to be patronising or preaching. A lack of consensus
      between age and sex groups highlighted a need for multifaceted, multi-modal
      approaches that utilise mobile technologies and new media. 

PMID- 23947784
TI  - Progression of bone metastases in patients with prostate cancer - automated
      detection of new lesions and calculation of bone scan index.
AB  - BACKGROUND: The objective of this study was firstly to develop and evaluate an
      automated method for the detection of new lesions and changes in bone scan index
      (BSI) in serial bone scans and secondly to evaluate the prognostic value of the
      method in a group of patients receiving chemotherapy. METHODS: The automated
      method for detection of new lesions was evaluated in a group of 266 patients
      using the classifications by three experienced bone scan readers as a gold
      standard. The prognostic value of the method was assessed in a group of 31
      metastatic hormone-refractory prostate cancer patients who were receiving
      docetaxel. Cox proportional hazards were used to investigate the association
      between percentage change in BSI, number of new lesions and overall survival.
      Kaplan-Meier estimates of the survival function were used to indicate a
      significant difference between patients with an increase/decrease in BSI or those
      with two or more new lesions or less than two new lesions. RESULTS: The automated
      method detected progression defined as two or more new lesions with a sensitivity
      of 93% and a specificity of 87%. In the treatment group, both BSI changes and the
      number of new metastases were significantly associated with survival. Two-year
      survival for patients with increasing and decreasing BSI from baseline to follow
      up scans were 18% and 57% (p = 0.03), respectively. Two-year survival for
      patients fulfilling and not fulfilling the criterion of two or more new lesions
      was 35% and 38% (n.s.), respectively. CONCLUSIONS: An automated method can be
      used to calculate the number of new lesions and changes in BSI in serial bone
      scans. These imaging biomarkers contained prognostic information in a small group
      of patients with prostate cancer receiving chemotherapy.

PMID- 23947785
TI  - Aurintricarboxylic acid modulates the affinity of hepatitis C virus NS3 helicase
      for both nucleic acid and ATP.
AB  - Aurintricarboxylic acid (ATA) is a potent inhibitor of many enzymes needed for
      cell and virus replication, such as polymerases, helicases, nucleases, and
      topoisomerases. This study examines how ATA interacts with the helicase encoded
      by the hepatitis C virus (HCV) and reveals that ATA interferes with both nucleic
      acid and ATP binding to the enzyme. We show that ATA directly binds HCV helicase
      to prevent the enzyme from interacting with nucleic acids and to modulate the
      affinity of HCV helicase for ATP, the fuel for helicase action. Amino acid
      substitutions in the helicase DNA binding cleft or its ATP binding site alter the
      ability of ATA to disrupt helicase-DNA interactions. These data, along with
      molecular modeling results, support the notion that an ATA polymer binds between
      Arg467 and Glu493 to prevent the helicase from binding either ATP or nucleic
      acids. We also characterize how ATA affects the kinetics of helicase-catalyzed
      ATP hydrolysis, and thermodynamic parameters describing the direct interaction
      between HCV helicase and ATA using microcalorimetry. The thermodynamics of ATA
      binding to HCV helicase reveal that ATA binding does not mimic nucleic acid
      binding in that ATA binding is driven by a smaller enthalpy change and an
      increase in entropy. 

PMID- 23947786
TI  - Advancing a shared conversation to enhance health care enrollment in the United
      States-a timely opportunity and challenge for health literacy.

PMID- 23947787
TI  - Primary cerebral low-grade B-cell lymphoma, monoclonal immunoglobulin deposition
      disease, cerebral light chain deposition disease and "aggregoma": an update on
      classification and diagnosis.
AB  - BACKGROUND: This work aims to add evidence and provide an update on the
      classification and diagnosis of monoclonal immunoglobulin deposition disease
      (MIDD) and primary central nervous system low-grade lymphomas. MIDD is
      characterized by the deposition of light and heavy chain proteins. Depending on
      the spatial arrangement of the secreted proteins, light chain-derived amyloidosis
      (AL) can be distinguished from non-amyloid light chain deposition disease (LCDD).
      We present a case of an extremely rare tumoral presentation of LCDD (aggregoma)
      and review the 3 previously published LCDD cases and discuss their presentation
      with respect to AL. CASE PRESENTATION: A 61-year-old woman presented with a 31/2
      year history of neurologic symptoms due to a progressive white matter lesion of
      the left subcortical parieto-insular lobe and basal ganglia. 2 former
      stereotactic biopsies conducted at different hospitals revealed no evidence of
      malignancy or inflammation; thus, no therapy had been initiated. After performing
      physiological and functional magnetic resonance imaging (MRI), the tumor was
      removed under intraoperative monitoring at our department. Histological analysis
      revealed large amorphous deposits and small islands of lymphoid cells.
      CONCLUSION: LCCD is a very rare and obscure manifestation of primary central
      nervous system low-grade lymphomas that can be easily misdiagnosed by
      stereotactic biopsy sampling. If stereotactic biopsy does not reveal a definite
      result, a "wait-and-see" strategy can delay possible therapy for this disease.
      The impact of surgical removal, radiotherapy and chemotherapy in LCDD obviously
      remains controversial because of the low number of relevant cases.

PMID- 23947788
TI  - Programmed synthesis of a contiguous stereotriad motif by triple stereospecific
      reagent-controlled homologation.
AB  - All distinct diastereoisomers of a contiguous stereotriad motif were separately
      targeted by a triple chain extension of B-phenethyl boronic esters using four
      unique presentation sequences of enantiomorphs of 1-[(2)H]-1-chloro-2-(1,3
      dioxolan-2-yl)ethyllithium. The (R)- or (S)-configured chloroalkyllithium
      reagents were generated by sulfoxide-lithium exchange from the appropriate
      scalemic p-tolyl chloroalkyl sulfoxides using phenyllithium (THF, -78  degrees
      C). Stereotriad synthesis was accomplished in a single reaction vessel [7-19%
      yield, typical dr >= 74 (target):26 (? all other isomers)] and implemented by a
      simple algorithm consisting of reagent charging and temperature cycling events. 

PMID- 23947790
TI  - Silver nanoparticle decorated reduced graphene oxide (rGO) nanosheet: a platform
      for SERS based low-level detection of uranyl ion.
AB  - Herein, a simple wet-chemical pathway has been demonstrated for the synthesis of
      silver nanoparticle conjugated reduced graphene oxide nanosheets where
      dimethylformamide (DMF) is judiciously employed as an efficient reducing agent.
      Altogether, DMF reduces both silver nitrate (AgNO3) and graphene oxide (GO) in
      the reaction mixture. Additionally, the presence of polyvinylpyrolidone (PVP)
      assists the nanophasic growth and homogeneous distribution of the plasmonic
      nanoparticle Ag(0). Reduction of graphene oxide and the presence of aggregated Ag
      NPs on reduced graphene oxide (rGO) nanosheets are confirmed from various
      spectroscopic techniques. Finally, the composite material has been exploited as
      an intriguing platform for surface enhanced Raman scattering (SERS) based
      selective detection of uranyl (UO2(2+)) ion. The limit of detection has been
      achieved to be as low as 10 nM. Here the normal Raman spectral (NRS) band of
      uranyl acetate (UAc) at 838 cm(-1) shifts to 714 and 730 cm(-1) as SERS bands for
      pH 5.0 and 12.0, respectively. This distinguished Raman shift of the symmetric
      stretching mode for UO2(2+) ion is indicative of pronounced charge transfer (CT)
      effect. This CT effect even supports the higher sensitivity of the protocol
      toward UO2(2+) over other tested oxo-ions. It is anticipated that rGO nanosheets
      furnish a convenient compartment to favor the interaction between Ag NPs and
      UO2(2+) ion through proximity induced adsorption even at low concentration. 

PMID- 23947791
TI  - Reference values for fetal tissue velocity imaging and a new approach to evaluate
      fetal myocardial function.
AB  - OBJECTIVES: Myocardial function can be evaluated using color-coded tissue
      velocity imaging (TVI) to analyze the longitudinal myocardial velocity profile,
      and by expressing the motion of the atrioventricular plane during a cardiac cycle
      as coordinated events in the cardiac state diagram (CSD). The objective of this
      study was to establish gestational age specific reference values for fetal TVI
      measurements and to introduce the CSD as a potential aid in fetal myocardial
      evaluation. METHODS: TVI recordings from 125 healthy fetuses, at 18 to 42 weeks
      of gestation, were performed with the transducer perpendicular to the apex to
      provide a four-chamber view. The myocardial velocity data was extracted from the
      basal segment of septum as well as the left and right ventricular free wall for
      subsequent offline analysis. RESULTS: During a cardiac cycle the longitudinal
      peak velocities of septum increased with gestational age, as did the peak
      velocities of the left and right ventricular free wall, except for the peak
      velocity of post ejection. The duration of rapid filling and atrial contraction
      increased during pregnancy while the duration of post ejection decreased. The
      duration of pre ejection and ventricular ejection did not change significantly
      with gestational age. CONCLUSION: Evaluating fetal systolic and diastolic
      performance using TVI together with CSD could contribute to increase the
      knowledge and understanding of fetal myocardial function and dysfunction. The pre
      and post ejection phases are the variables most likely to indicate fetuses with
      abnormal myocardial function.

PMID- 23947792
TI  - Concurrent and prospective associations of habitual overgeneral memory and
      prospection with symptoms of depression, general anxiety, obsessive
      compulsiveness, and post-traumatic stress.
AB  - Reduced memory specificity is associated with depression, post-traumatic stress
      disorder (PTSD), and some other forms of psychopathology. Reduced memory
      specificity is also associated with reduced specificity of envisioned future
      events. Research in this area has mostly relied on cue-word methods that include
      explicit instructions to develop specific memories of future events. These
      methods are limited in their ability to assess how participants habitually
      remember the past and imagine the future when the specificity constraints
      inherent in the cue-word task are removed. Sentence completions tasks have been
      developed that can be used to assess habitual patterns of memory and prospection.
      Little is known about the association of habitual memory and prospection with
      concurrently and prospectively assessed psychopathology. In the current study 142
      participants completed sentence completion tasks tapping habitual memory and
      prospection at baseline and completed measures tapping psychological symptoms at
      baseline and 1 year later. Among other things, it was found that reduced memory
      specificity (but not reduced future specificity) was associated with concurrent
      and later depression, as well as with symptom levels of PTSD tapped 1 year beyond
      baseline.

PMID- 23947793
TI  - Effect of the alcohol consumption on osteocyte cell processes: a molecular
      imaging study.
AB  - We have previously shown microarchitectural tissue changes with cellular
      modifications in osteocytes following high chronic alcohol dose. The aim of this
      study was to assess the dose effect of alcohol consumption on the cytoskeleton
      activity, the cellular lipid content and modulation of differentiation and
      apoptosis in osteocyte. Male Wistar rats were divided into three groups: Control
      (C), Alcohol 25% v/v (A25) or Alcohol 35% v/v (A35) for 17 weeks. Bone mineral
      density (BMD) was assessed by DXA, osteocyte empty lacunae, lacunae surface, bone
      marrow fat with bright field microscopy. Osteocyte lipid content was analysed
      with transmission electron microscopy (TEM) and epifluorescence microscopy.
      Osteocyte apoptosis was analysed with immunolabelling and TEM. Osteocyte
      differentiation and cytoskeleton activity were analysed with immunolabelling and
      real time quantitative PCR. At the end of the protocol, BMD was lower in A25 and
      A35 compared with C, while the bone marrow lipid content was increased in these
      groups. More empty osteocyte lacunae and osteocyte containing lipid droplets in
      A35 were found compared with C and A25. Cleaved caspase-3 staining and chromatin
      condensation were increased in A25 and A35 versus C. Cleaved caspase-3 was
      increased in A35 versus A25. CD44 and phosphopaxillin stainings were higher in
      A35 compared with C and A25. Paxillin mRNA expression was higher in A35 versus
      A25 and C and sclerostin mRNA expression was higher in A35 versus C. We only
      observed a dose effect of alcohol consumption on cleaved caspase-3 osteocyte
      immunostaining levels and on the number of lipid droplets in the bone marrow.

PMID- 23947794
TI  - Herbimycins D-F, ansamycin analogues from Streptomyces sp. RM-7-15.
AB  - Bacterial strains belonging to the class actinomycetes were isolated from the
      soil near a thermal vent of the Ruth Mullins coal fire (Appalachian Mountains of
      eastern Kentucky). High-resolution electrospray ionization mass spectrometry and
      ultraviolet absorption profiles of metabolites from one of the isolates
      (Streptomyces sp. RM-7-15) revealed the presence of a unique set of metabolites
      ultimately determined to be herbimycins D-F (1-3). In addition, herbimycin A (4),
      dihydroherbimycin A (TAN 420E) (7), and the structurally distinct antibiotic
      bicycylomycin were isolated from the crude extract of Streptomyces sp. RM-7-15.
      Herbimycins A and D-F (1-3) displayed comparable binding affinities to the
      Hsp90alpha. While the new analogues were found to be inactive in cancer cell
      cytotoxicity and antimicrobial assays, they may offer new insights in the context
      of nontoxic ansamycin-based Hsp90 inhibitors for the treatment of
      neurodegenerative disease. 

PMID- 23947795
TI  - Intravenous lidocaine suppresses fentanyl-induced cough in Children.
AB  - OBJECTIVE: Fentanyl-induced cough is usually mild and transitory, but it can be
      undesirable in patients with increased intracranial pressure, open wounds of the
      eye, dissecting aortic aneurism, pneumothorax, and reactive airway disease. The
      aim of this study is to evaluate the efficacy of lidocaine in suppressing
      fentanyl-induced cough in children during induction in general anesthesia.
      METHODS: One hundred and eighty-six children of both sexes, aged between 4-10
      years, ASA physical status I and II, and scheduled for elective surgery, were
      recruited for the study. Patients with a history of bronchial asthma, obstructive
      pulmonary disease, or infections of the respiratory tract were excluded. Patients
      were randomly allocated to three equal groups (n = 62) to receive 1.0 mg/kg
      lidocaine (Group I), 0.5 mg/kg lidocaine (Group II), or placebo (equal volume of
      0.9% saline; Group III). Each was administered over 5 s one minute before
      intravenous (IV) administration of fentanyl 2-3 MUg/kg during induction in
      general anesthesia. The severity of coughing was graded by counting the number of
      episodes of cough: mild (1-2), moderate (3-4) or severe (5 or more). RESULTS:
      Demographic information was comparable between groups. The most frequent coughing
      was observed in the placebo group (Group III; 43.5%), of whom 4.8% (three
      patients) were graded with severe cough. In Group II, 22.6% patients had cough,
      of which 1.6% (one patient) was graded as severe. In Group I, 16.1% patients had
      cough, none of whom were graded as severe. CONCLUSION: Our results demonstrate
      that IV lidocaine can markedly suppress fentanyl-induced cough in children, even
      in doses as low as 0.5 mg/kg.

PMID- 23947796
TI  - Aggregation kinetics of manganese dioxide colloids in aqueous solution: influence
      of humic substances and biomacromolecules.
AB  - In this work, the early stage aggregation kinetics of manganese dioxide (MnO2)
      colloids in aqueous solution and the effects of constituents of natural organic
      matter (i.e., Suwannee River fulvic acid (SRFA), Suwannee River humic acid
      (SRHA), alginate, and bovine serum albumin (BSA)) were investigated by time
      resolved dynamic light scattering. MnO2 colloids were significantly aggregated in
      the presence of monovalent and divalent cations. The critical coagulation
      concentrations were 28, 0.8, and 0.45 mM for NaNO3, Mg(NO3)2, and Ca(NO3)2,
      respectively. The Hamaker constant of MnO2 colloids in aqueous solution was 7.84
      * 10(-20) J. All the macromolecules tested slowed MnO2 colloidal aggregation
      rates greatly. The steric repulsive forces, originated from organic layers
      adsorbed on MnO2 colloidal surfaces, may be mainly responsible for their
      stabilizing effects. However, the complexes formed by alginate and Ca(2+) (>5 mM)
      might play a bridging role and thus enhanced MnO2 colloidal aggregation instead.
      These results may be important for assessing the fate and transport of MnO2
      colloids and associated contaminants. 

PMID- 23947797
TI  - Modelling the cost-effectiveness of preventing major depression in general
      practice patients.
AB  - BACKGROUND: The prevention of depression is a key public health policy priority.
      PredictD is the first risk algorithm for the prediction of the onset of major
      depression. Our aim in this study was to model the cost-effectiveness of PredictD
      in depression prevention in general practice (GP). METHOD: A decision analytical
      model was developed to determine the cost-effectiveness of two approaches, each
      of which was compared to treatment as usual (TAU) over 12 months: (1) the
      PredictD risk algorithm plus a low-intensity depression prevention programme; and
      (2) a universal prevention programme in which there was no initial identification
      of those at risk. The model simulates the incidence of depression and disease
      progression over 12 months and calculates the net monetary benefit (NMB) from the
      National Health Service (NHS) perspective. RESULTS: Providing patients with
      PredictD and a depression prevention programme prevented 15 (17%) cases of
      depression in a cohort of 1000 patients over 12 months and had the highest
      probability of being the optimal choice at a willingness to pay (WTP) of L20,000
      for a quality-adjusted life year (QALY). Universal prevention was strongly
      dominated by PredictD plus a depression prevention programme in that universal
      prevention resulted in less QALYs than PredictD plus prevention for a greater
      cost. CONCLUSIONS: Using PredictD to identify primary-care patients at high risk
      of depression and providing them with a low-intensity prevention programme is
      potentially cost-effective at a WTP of L20,000 per QALY.

PMID- 23947798
TI  - Absorption cross sections of surface-adsorbed H2O in the 295-370 nm region and
      heterogeneous nucleation of H2O on fused silica surfaces.
AB  - We have determined absorption cross sections of a monolayer of H2O adsorbed on
      the fused silica surfaces in the 295-370 nm region at 293 +/- 1 K by using
      Brewster angle cavity ring-down spectroscopy. Absorption cross sections of
      surface-adsorbed H2O vary between (4.66 +/- 0.83) * 10(-20) and (1.73 +/- 0.52) *
      10(-21) cm(2)/molecule over this wavelength range, where errors quoted represent
      experimental scatter (1sigma). Our experimental study provides direct evidence
      that surface-adsorbed H2O is an absorber of the near UV solar radiation. We also
      varied the H2O pressure in the surface study cell over the 0.01-17 Torr range and
      obtained probe laser absorptions at 295, 340, and 350 nm by multilayer of
      adsorbed H2O molecules until the heterogeneous nucleation of water occurred on
      fused silica surfaces. The average absorption cross sections of multilayer
      adsorbed H2O are (2.17 +/- 0.53) * 10(-20), (2.48 +/- 0.67) * 10(-21), and (2.34
      +/- 0.59) * 10(-21) cm(2)/molecule at 295, 340, and 350 nm. The average
      absorption cross sections of transitional H2O layer are (6.06 +/- 2.73) * 10(
      20), (6.48 +/- 3.85) * 10(-21), and (8.04 +/- 4.92) * 10(-21) cm(2)/molecule at
      295, 340, and 350 nm. The average thin water film absorption cross sections are
      (2.39 +/- 0.50) * 10(-19), (3.21 +/- 0.81) * 10(-20), and (3.37 +/- 0.94) * 10(
      20) cm(2)/molecule at 295 nm, 340 nm, and 350 nm. Atmospheric implications of the
      results are discussed. 

PMID- 23947799
TI  - Will student debt impact our specialty?

PMID- 23947801
TI  - Functional improvements desired by patients before and in the first year after
      total hip arthroplasty.
AB  - BACKGROUND: In the field of rehabilitation, patients are supposed to be experts
      on their own lives, but the patient's own desires in this respect are often not
      reported. Our objectives were to describe the patients' desires regarding
      functional improvements before and after total hip arthroplasty (THA). METHODS:
      Sixty-four patients, 34 women and 30 men, with a mean age of 65 years, were asked
      to describe in free text which physical functions they desired to improve. They
      were asked before surgery and at three and 12 months after surgery. Each response
      signified one desired improvement. The responses were coded according to the
      International Classification of Functioning, Disability and Health (ICF) to the
      1st, 2nd and 3rd category levels. The frequency of the codes was calculated as a
      percentage of the total number of responses of all assessments times and in
      percentage of each time of assessment. RESULTS: A total of 333 responses were
      classified under Part 1 of the ICF, Functioning and Disability, and 88% of the
      responses fell into the Activities and Participation component. The numbers of
      responses classified into the Activities and Participation component were
      decreasing over time (p < 0.001). The categories of Walking (d450), Moving around
      (d455), and Recreation and leisure (d920) included more than half of the
      responses at all the assessment times. At three months after surgery, there was a
      trend that fewer responses were classified into the Recreation and leisure
      category, while more responses were classified into the category of Dressing
      (d540). CONCLUSIONS: The number of functional improvements desired by the
      patients decreased during the first postoperative year, while the content of the
      desires before and one year after THA were rather consistent over time and mainly
      concerned with the ability to walk and participate in recreation and leisure
      activities. At three months, however, there was a tendency that the patients were
      more concerned about the immediate problems with putting on socks and shoes.

PMID- 23947802
TI  - Spatial and temporal effects in protein post-translational modification
      distributions in the developing mouse brain.
AB  - Protein post-translational modification (PTM) is a powerful way to modify the
      behavior of cellular proteins and thereby cellular behavior. Multiple recent
      studies of evolutionary trends have shown that certain pairs of protein post
      translational modifications tend to occur closer to each other than expected at
      random. This type of observation may form the basis of a proposed "PTM code",
      whereby protein function is controlled by complex patterns of multiple PTMs. This
      code could provide an additional, powerful level of regulatory control for
      protein function and is a plausible explanation for observations of increasingly
      frequent and diverse protein modification in cell biology. In this study, we use
      mass spectrometry and proteomic strategies to present biological data showing
      spatiotemporal PTM co-localization across multiple PTM categories, which display
      changes over development of the brain. This may be an indication of the existence
      of a PTM-based functional coding mechanism, which would significantly expand our
      view of the ways in which cells use protein PTMs in complex signaling networks. 

PMID- 23947804
TI  - Antioxidant and antidiabetic activities of black mung bean (Vigna radiata L.).
AB  - Interest in mung bean as a functional food is growing. The objective of this
      study was to characterize the phenolic compounds, antioxidant activities, and
      antidiabetic activities of black mung beans. Five black mung beans were selected,
      and one green mung bean was included for comparison. The free phenolic acid and
      bound phenolic acid contents ranged from 16.68 to 255.51 MUg/g and from 2284.53
      to 5363.75 MUg/g, respectively, whereas the total anthocyanin contents ranged
      from 0 to 810.55 MUg/g with cyanidin-3-glucoside as the most dominant form,
      respectively. Among the mung beans tested, black mug bean Xiaoqu 7110 had the
      highest content of bound phenolic acids and exhibited the strongest antioxidant
      capacities (1,1-diphenyl-2-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6
      sulfonic acid) diammonium salt and oxygen radical absorbance capacity) as
      compared to the other tested mung beans. Jiheilv 27-3 exhibited higher
      antidiabetic activities (inhibition of alpha-glucosidase and advanced glycation
      end products). 

PMID- 23947803
TI  - HIF-1alpha/GPER signaling mediates the expression of VEGF induced by hypoxia in
      breast cancer associated fibroblasts (CAFs).
AB  - INTRODUCTION: Carcinoma-associated fibroblasts (CAFs) play a pivotal role in
      cancer progression by contributing to invasion, metastasis and angiogenesis.
      Solid tumors possess a unique microenvironment characterized by local hypoxia,
      which induces gene expression changes and biological features leading to poor
      outcomes. Hypoxia Inducible Factor 1 (HIF-1) is the main transcription factor
      that mediates the cell response to hypoxia through different mechanisms that
      include the regulation of genes strongly associated with cancer aggressiveness.
      Among the HIF-1 target genes, the G-protein estrogen receptor (GPER) exerts a
      stimulatory role in diverse types of cancer cells and in CAFs. METHODS: We
      evaluated the regulation and function of the key angiogenic mediator vascular
      endothelial growth factor (VEGF) in CAFs exposed to hypoxia. Gene expression
      studies, Western blotting analysis and immunofluorescence experiments were
      performed in CAFs and breast cancer cells in the presence of cobalt chloride
      (CoCl2) or cultured under low oxygen tension (2% O2), in order to analyze the
      involvement of the HIF-1alpha/GPER signaling in the biological responses to
      hypoxia. We also explored the role of the HIF-1alpha/GPER transduction pathway in
      functional assays like tube formation in human umbilical vein endothelial cells
      (HUVECs) and cell migration in CAFs. RESULTS: We first determined that hypoxia
      induces the expression of HIF-1alpha and GPER in CAFs, then we ascertained that
      the HIF-1alpha/GPER signaling is involved in the regulation of VEGF expression in
      breast cancer cells and in CAFs exposed to hypoxia. We also assessed by ChIP
      assay that HIF-1alpha and GPER are both recruited to the VEGF promoter sequence
      and required for VEGF promoter stimulation upon hypoxic condition. As a
      biological counterpart of these findings, conditioned medium from hypoxic CAFs
      promoted tube formation in HUVECs in a HIF-1alpha/GPER dependent manner. The
      functional cooperation between HIF-1alpha and GPER in CAFs was also evidenced in
      the hypoxia-induced cell migration, which involved a further target of the HIF
      1alpha/GPER signaling like connective tissue growth factor (CTGF). CONCLUSIONS:
      The present results provide novel insight into the role elicited by the HIF
      1alpha/GPER transduction pathway in CAFs towards the hypoxia-dependent tumor
      angiogenesis. Our findings further extend the molecular mechanisms through which
      the tumor microenvironment may contribute to cancer progression.

PMID- 23947805
TI  - Effort and negative affect interact to predict cardiovascular responses to
      stress.
AB  - OBJECTIVE: Although traditional models posit that negative emotional responses to
      stress increase cardiovascular reactivity (CVR), laboratory studies have
      generally not found a strong emotion-CVR association. In this paper, we took a
      multidimensional approach to examining psychological reactions to stress in three
      studies. METHODS: In each study we assessed the amount of effort exerted by a
      participant and the negative affect (NA) felt by the participant with different
      self-reported measures and an effort behavioural measure. RESULTS: Our findings
      consistently demonstrated that NA was associated with CVR when effort was
      relatively high, but not when effort was relatively low. CONCLUSION: This
      suggests that the weak NA-CVR correlations reported in past research may have
      been confounded by a third effort-related variable and that CVR is significantly
      associated with NA under certain circumstances. Furthermore, our findings suggest
      that by considering the multidimensional nature of psychological responses to
      stress, we may come to better understand the links between stress-related emotion
      and physiology.

PMID- 23947806
TI  - Work and rest variables in the acquisition of psychomotor tracking skill.
AB  - College students (75 men, 75 women) matched in preliminary performance of 100 sec
      on the rotary pursuit apparatus were randomly assigned to five experimental
      groups. Their work/rest ratios, measured in seconds, were: 20/20, 30/30, 60/60,
      90/90,120/120. All subjects received 30 min of total practice time after the
      matching trial. There was a significant practice effect and a significant
      practice x conditions interaction, but no main effect due to the cycles' length
      or number. The decay rate of reactive inhibition (lr) is probably independent of
      its prior growth level; hence postrest residual lr is proportional to prerest
      accumulation. Partly because they generated lr in hypothetically greater amounts,
      women were significantly less proficient on the average than men, and sex
      interacted with practice. Although males had higher initial and final levels of
      ability than females, the two sexes' acquisition curves showed the same rate
      parameters in our mathematical model. 

PMID- 23947807
TI  - Motor schema formation and retention in young children.
AB  - The variability-of-practice hypothesis, a major prediction of Schmidt's (1975)
      motor schema theory, was tested in an attempt to investigate motor-schema
      formation. In addition, schema retention was observed after a 2-week retention
      interval. The task involved preschool children in tossing a bean bag for
      appropriate distance. Four treatment groups received 100 practice trials equally
      divided over five days. Variation was provided by varying the weights of the bean
      bags. The testing situations involved tossing a criterion weighted bean bag as
      well as a novel weighted bean bag which none of the groups had experienced
      previously. In addition, all groups were tested on a new but similar task. The
      results supported the variability-of-practice hypothesis in terms of schema
      formation and transfer to novel tasks in the same movement class. After a two
      week retention interval, loss in performance was significantly less for the group
      with variability of practice than all other groups. 

PMID- 23947808
TI  - Reactive inhibition theory and intertrial correlations.
AB  - From certain theoretical properties of Hull's reactive inhibition and from the
      known modest reliability of reminiscence measures, it follows that intertrial
      correlations among psychomotor test scores should be higher under distributed
      practice conditions than under massed-practice conditions. This proposition was
      tested in a conventional practice distribution paradigm involving 168 Caucasian
      subjects. Bartlett's test for the homogeneity of covariance matrices confirmed
      the prediction, and a sign test for matched correlation pairs showed that
      correlations in the distributed practice mode were significantly more often
      higher than those in the massed practice mode. These results refute the
      prevailing view that intertrial correlations are invariant with respect to
      practice distribution, and they strengthen the credibility of Hull's principle of
      reactive inhibition. 

PMID- 23947809
TI  - Perceived task complexity and reaction time on a single trial and a series of
      trials.
AB  - The time required to begin movement toward a panel of lights and switches of two
      different complexity levels was investigated in both a between-subjects and
      within-subjects design. In the between-subjects design, the mean RT on the
      subjects' first trial was longer to the more complex task, supporting the memory
      drum theory of Henry and Rogers (1960). In the within-subjects design, a
      significant complexity x order x blocks interaction showed that the subjects
      receiving the less complex task first responded differently than subjects
      receiving the more complex task first. Implications for experimental design in
      investigations of task complexity are discussed. 

PMID- 23947810
TI  - Is reaction time different for long and short response durations in simple and
      choice conditions?
AB  - Subjects pressed a key down as fast as possible but controlled the response
      duration of the keypress. The task required long (300 +/-100 msec) and short
      (150+/-50 msec) durations in both simple (long only or short only) and choice
      (mixed long and short) conditions. Choice reaction time was slower than simple
      reaction time, but reaction time for long and short durations did not differ
      significantly for either simple or choice conditions. This finding fails to
      support a study by Klapp, Wyatt, and Lingo (1974) which found reaction time
      differences between long and short durations for choice but not simple
      conditions. 

PMID- 23947811
TI  - Manufacturing repetition effects- a reply to gentile and nemetz (1978).
AB  - Under the guise of repetition effects, Gentile and Nemetz (1978) vociferously
      attack the explanatory power and utility of short-term motor memory research.
      Such a criticism is based on the belief that treatment effects are confounded
      with learning effects in experiments which require subjects to constantly
      reproduce invariant target positions. In this note a systematic critique of
      Gentile and Nemetz's logic and experimental evidence illuminates the questionable
      status of their position. It is argued that the Gentile and Nemetz findings
      actually oppose the existence of the procedural artifact they would have us
      consider. On the basis of methodological and logical arguments presented, it is
      concluded that a properly designed experiment need not be confounded by
      repetition effects. Finally, guidelines on both the manufacture and avoidance of
      repetition effects are suggested. 

PMID- 23947812
TI  - Compression block studies and the closed-loop system.
AB  - The Chambers and Schumsky (1978) study was not an experiment crucius regarding
      the Laszlo-Bairstow closed-loop theory. Yet, serious questions still exist about
      the contribution of motor impairment in general, and anoxia in particular, to
      results of motor block studies. 

PMID- 23947813
TI  - The compression-block technique.
AB  - Two points were made in support of the compression-block technique as a useful
      tool in motor-control research. The effect of motor impairment (if any) can be
      controlled (a) by only making direct comparisons between results obtained under
      block, and (b) by keeping muscle exertion during the entire course of the block
      to an absolute minimum to avoid muscle fatigue. 

PMID- 23947814
TI  - Structural characterization of more potent alternatives to HAMLET, a tumoricidal
      complex of alpha-lactalbumin and oleic acid.
AB  - HAMLET is a complex of human alpha-lactalbumin (hLA) with oleic acid (OA) that
      kills various tumor cells and strains of Streptococcus pneumoniae. More potent
      protein-OA complexes were previously reported for bovine alpha-lactalbumin (bLA)
      and beta-lactoglobulin (bLG), and pike parvalbumin (pPA), and here we explore
      their structural features. The concentration dependencies of the tryptophan
      fluorescence of hLA, bLA, and bLG complexes with OA reveal their disintegration
      at protein concentrations below the micromolar level. Chemical cross-linking
      experiments provide evidence that association with OA shifts the distribution of
      oligomeric forms of hLA, bLA, bLG, and pPA toward higher-order oligomers. This
      effect is confirmed for bLA and bLG using the dynamic light scattering method,
      while pPA is shown to associate with OA vesicles. Like hLA binding, OA binding
      increases the affinity of bLG for small unilamellar
      dipalmitoylphosphatidylcholine vesicles, while pPA efficiently binds to the
      vesicles irrespective of OA binding. The association of OA with bLG and pPA
      increases their alpha-helix and cross-beta-sheet content and resistance to
      enzymatic proteolysis, which is indicative of OA-induced protein structuring. The
      lack of excess heat sorption during melting of bLG and pPA in complex with OA and
      the presence of a cooperative thermal transition at the level of their secondary
      structure suggest that the OA-bound forms of bLG and pPA lack a fixed tertiary
      structure but exhibit a continuous thermal transition. Overall, despite marked
      differences, the HAMLET-like complexes that were studied exhibit a common
      feature: a tendency toward protein oligomerization. Because OA-induced
      oligomerization has been reported for other proteins, this phenomenon is inherent
      to many proteins. 

PMID- 23947815
TI  - Molecular fingerprinting reflects different histotypes and brain region in low
      grade gliomas.
AB  - BACKGROUND: Paediatric low-grade gliomas (LGGs) encompass a heterogeneous set of
      tumours of different histologies, site of lesion, age and gender distribution,
      growth potential, morphological features, tendency to progression and clinical
      course. Among LGGs, Pilocytic astrocytomas (PAs) are the most common central
      nervous system (CNS) tumours in children. They are typically well-circumscribed,
      classified as grade I by the World Health Organization (WHO), but recurrence or
      progressive disease occurs in about 10-20% of cases. Despite radiological and
      neuropathological features deemed as classic are acknowledged, PA may present a
      bewildering variety of microscopic features. Indeed, tumours containing both
      neoplastic ganglion and astrocytic cells occur at a lower frequency. METHODS:
      Gene expression profiling on 40 primary LGGs including PAs and mixed glial
      neuronal tumours comprising gangliogliomas (GG) and desmoplastic infantile
      gangliogliomas (DIG) using Affymetrix array platform was performed. A
      biologically validated machine learning workflow for the identification of
      microarray-based gene signatures was devised. The method is based on a sparsity
      inducing regularization algorithm l1l2 that selects relevant variables and takes
      into account their correlation. The most significant genetic signatures emerging
      from gene-chip analysis were confirmed and validated by qPCR. RESULTS: We
      identified an expression signature composed by a biologically validated list of
      15 genes, able to distinguish infratentorial from supratentorial LGGs. In
      addition, a specific molecular fingerprinting distinguishes the supratentorial
      PAs from those originating in the posterior fossa. Lastly, within supratentorial
      tumours, we also identified a gene expression pattern composed by neurogenesis,
      cell motility and cell growth genes which dichotomize mixed glial-neuronal
      tumours versus PAs. Our results reinforce previous observations about aberrant
      activation of the mitogen-activated protein kinase (MAPK) pathway in LGGs, but
      still point to an active involvement of TGF-beta signaling pathway in the PA
      development and pick out some hitherto unreported genes worthy of further
      investigation for the mixed glial-neuronal tumours. CONCLUSIONS: The
      identification of a brain region-specific gene signature suggests that LGGs, with
      similar pathological features but located at different sites, may be
      distinguishable on the basis of cancer genetics. Molecular fingerprinting seems
      to be able to better sub-classify such morphologically heterogeneous tumours and
      it is remarkable that mixed glial-neuronal tumours are strikingly separated from
      PAs.

PMID- 23947816
TI  - Formation and physicochemical properties of crystalline and amorphous salts with
      different stoichiometries formed between ciprofloxacin and succinic acid.
AB  - Multi-ionizable compounds, such as dicarboxylic acids, offer the possibility of
      forming salts of drugs with multiple stoichiometries. Attempts to crystallize
      ciprofloxacin, a poorly water-soluble, amphoteric molecule with succinic acid (S)
      resulted in isolation of ciprofloxacin hemisuccinate (1:1) trihydrate (CHS-I) and
      ciprofloxacin succinate (2:1) tetrahydrate (CS-I). Anhydrous ciprofloxacin
      hemisuccinate (CHS-II) and anhydrous ciprofloxacin succinate (CS-II) were also
      obtained. It was also possible to obtain stoichiometrically equivalent amorphous
      salt forms, CHS-III and CS-III, by spray drying and milling, respectively, of the
      drug and acid. Anhydrous CHS and CS had melting points at ~215 and ~228  degrees
      C, while the glass transition temperatures of CHS-III and CS-III were ~101 and
      ~79  degrees C, respectively. Dynamic solubility studies revealed the metastable
      nature of CS-I in aqueous media, resulting in a transformation of CS-I to a mix
      of CHS-I and ciprofloxacin 1:3.7 hydrate, consistent with the phase diagram. CS
      III was observed to dissolve noncongruently leading to high and sustainable drug
      solution concentrations in water at 25 and 37  degrees C, with the ciprofloxacin
      concentration of 58.8+/-1.18 mg/mL after 1 h of the experiment at 37  degrees C.
      This work shows that crystalline salts with multiple stoichiometries and
      amorphous salts have diverse pharmaceutically relevant properties, including
      molecular, solid state, and solubility characteristics.

PMID- 23947818
TI  - Genetic analysis of noroviruses associated with sporadic gastroenteritis during
      winter in Guangzhou, China.
AB  - Noroviruses are regarded as the major causes of acute gastroenteritis worldwide,
      but their prevalence in sporadic diarrhea in South China remains unclear. This
      study was performed to characterize the genotypes of circulating norovirus
      strains associated with sporadic diarrhea cases in Guangzhou from November 2010
      to January 2011. Among fecal specimens collected from 89 patients with acute
      diarrhea, nine samples (10.11%) were norovirus positive and 32 samples (35.96%)
      were rotavirus positive. The partial polymerase and the capsid regions of these
      norovirus samples were sequenced and phylogenetically analyzed. Three genotypes
      (GII.4, GII.6, and GII.b/GII.3) were identified, among which GII.4-2006b was the
      most predominant genotype (4/9, 44.4%), followed by GII.6 (3/9, 33.3%). A novel
      GII.4-2010 variant was first detected in China. Furthermore, the near full-length
      genome of the GZ2010-L26 strain, which belonged to GII.4-2006b, was sequenced and
      analyzed. Thus, the results of this study suggested that, second to rotavirus,
      noroviruses are the important pathogens responsible for sporadic acute
      gastroenteritis during winter in Guangzhou, and the GII.4-2006b variant remains
      the predominant genotype.

PMID- 23947819
TI  - Rapid oligonucleotide suspension array-based multiplex detection of bacterial
      pathogens.
AB  - A gene-specific microsphere suspension array coupled with 15-plex polymerase
      chain reaction (PCR) was developed to screen bacterial samples rapidly for 10
      strains of bacteria: Shigella spp. (S. flexneri, S. dysenteriae, and S. sonnei),
      Staphylococcus aureus, Vibrio cholerae (serology O1 and O139), Legionella
      pneumophila, and Clostridium botulinum (types A, B, and E). Fifteen sets of
      highly validated primers were chosen to amplify target genes simultaneously.
      Corresponding oligonucleotide probes directly conjugated with microsphere sets
      were used to specifically identify PCR amplicons. Sensitivity tests revealed that
      the array coupled with single PCR was able to detect purified genomic DNA at
      concentrations as low as 10 copies/MUL, while the multiplex detection limit was
      10-104 copies/MUL. The assay was validated using water samples artificially
      spiked with S. aureus and S. dysenteriae, as well as water specimens from
      swimming pools previously identified to contain S. aureus.

PMID- 23947820
TI  - Asymmetric epoxidation of alkenes catalyzed by a porphyrin-inspired manganese
      complex.
AB  - A novel strategy for catalytic asymmetric epoxidation of a wide variety of
      olefins by a porphyrin-inspired chiral manganese complex using H2O2 as a terminal
      oxidant in excellent yield with up to greater than 99% ee has been successfully
      developed. 

PMID- 23947821
TI  - Protective and antidiabetic effects of extract from Nigella sativa on blood
      glucose concentrations against streptozotocin (STZ)-induced diabetic in rats: an
      experimental study with histopathological evaluation.
AB  - BACKGROUND: Diabetes in humans induces chronic complications such as
      cardiovascular damage, cataracts and retinopathy, nephropathy and polyneuropathy.
      The most common animal model of human diabetes is streptozotocin (STZ)-induced
      diabetes in the rat. The present study investigated the effects of Nigella sativa
      hydroalcholic extract on glucose concentrations in streptozotocin (STZ) diabetic
      rats. METHODS: In this study Twenty-five Wister-Albino rats (aged 8-9 weeks and
      weighing 200-250 g) were tested. Rats were divided into five experimental groups
      (control, untreated STZ-diabetic (60 mg/kg B.W., IP), treated STZ-diabetic with
      hydroalcholic extract of Nigella Sativa (NS) (5 mg/kg B.W, IP), treated STZ
      diabetic with hydroalcholic extract of NS (10 mg/kg B.W., IP) and treated STZ
      diabetic with hydroalcholic extract of NS (20 mg/kg B.W., IP and 32 days were
      evaluated to assess its effect on fasting blood glucose (FBG), and in different
      groups fasting blood glucose (FBG) and body weight (BW) were measured in the
      particular days (1, 16 and 32). At the end of the study, the animals were fasted
      overnight, anaesthetized with an intraperitoneal injection of sodium
      pentobarbital (60 mg/kg), and sacrificed for obtaining tissues samples (liver,
      pancreases). The number of islets and cells were counted and the islet diameters
      were determined by calibrated micrometer. The glycogen content in the liver was
      examined by Periodic Acid-Schiff (PAS) staining. RESULTS: Treatment with NS (5
      mg/kg b.w.) markedly increased BW gain and the FBG level was significantly
      (p<0.001) reduced when compared to the control. Histopathological examination
      showed that the NS (5 mg/kg b.w.) partially recovered hepatic glycogen content
      and protected the great deal of the pancreatic islet cells. The number of islets,
      cells and islets diameter were found statistically significant when compared to
      the control (p<0.01, p<0.05). CONCLUSIONS: Higher doses of NS did not exhibit any
      therapeutic effect. These results showed that hydroalcholic extract of NS at low
      doses has hypoglycemic effect and ameliorative effect on regeneration of
      pancreatic islets and may be used as a therapeutic agent in the management of
      diabetes mellitus. The hypoglycemic effect observed could be due to amelioration
      of beta-cell, thus leading to increased insulin levels. Consequently, N. sativa
      may prove clinically useful in the treatment of diabetics and in the protection
      of beta-cells against streptozotocin. VIRTUAL SLIDE: The virtual slide(s) for
      this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1845133011104231.

PMID- 23947822
TI  - Research accomplishments in pediatric electrophysiology: a historical review.
AB  - Arrhythmia management in young patients plays a small but important role within
      the broader discipline of cardiac electrophysiology (EP). By virtue of its sharp
      focus on developmental cardiology, congenital heart defects, and hereditary
      channelopathies, pediatric EP has contributed in significant ways to improved
      understanding of rhythm disorders in patients of all ages. Scientific progress in
      the field was recently reviewed at the 2012 meeting of the Heart Rhythm Society,
      where historical details of pioneering investigations in pediatric EP were
      highlighted. In this article, we hope to summarize those details and acknowledge
      the roles of individuals and organizations that were instrumental in developing
      the subspecialty. 

PMID- 23947823
TI  - The influence of thematic congruency, typicality and divided attention on memory
      for radio advertisements.
AB  - We examined the effects of the thematic congruence between ads and the programme
      in which they are embedded. We also studied the typicality of the to-be
      remembered information (high- and low-typicality elements), and the effect of
      divided attention in the memory for radio ad contents. Participants listened to
      four radio programmes with thematically congruent and incongruent ads embedded,
      and completed a true/false recognition test indicating the level of confidence in
      their answer. Half of the sample performed an additional task (divided attention
      group) while listening to the radio excerpts. In general, recognition memory was
      better for incongruent ads and low-typicality statements. Confidence in hits was
      higher in the undivided attention group, although there were no differences in
      performance. Our results suggest that the widespread idea of embedding ads into
      thematic-congruent programmes negatively affects memory for ads. In addition, low
      typicality features that are usually highlighted by advertisers were better
      remembered than typical contents. Finally, metamemory evaluations were influenced
      by the inference that memory should be worse if we do several things at the same
      time.

PMID- 23947824
TI  - Geometrical correction for the inter- and intramolecular basis set superposition
      error in periodic density functional theory calculations.
AB  - We extend the previously developed geometrical correction for the inter- and
      intramolecular basis set superposition error (gCP) to periodic density functional
      theory (DFT) calculations. We report gCP results compared to those from the
      standard Boys-Bernardi counterpoise correction scheme and large basis set
      calculations. The applicability of the method to molecular crystals as the main
      target is tested for the benchmark set X23. It consists of 23 noncovalently bound
      crystals as introduced by Johnson et al. (J. Chem. Phys. 2012, 137, 054103) and
      refined by Tkatchenko et al. (J. Chem. Phys. 2013, 139, 024705). In order to
      accurately describe long-range electron correlation effects, we use the standard
      atom-pairwise dispersion correction scheme DFT-D3. We show that a combination of
      DFT energies with small atom-centered basis sets, the D3 dispersion correction,
      and the gCP correction can accurately describe van der Waals and hydrogen-bonded
      crystals. Mean absolute deviations of the X23 sublimation energies can be reduced
      by more than 70% and 80% for the standard functionals PBE and B3LYP,
      respectively, to small residual mean absolute deviations of about 2 kcal/mol
      (corresponding to 13% of the average sublimation energy). As a further test, we
      compute the interlayer interaction of graphite for varying distances and obtain a
      good equilibrium distance and interaction energy of 6.75 A and -43.0 meV/atom at
      the PBE-D3-gCP/SVP level. We fit the gCP scheme for a recently developed pob-TZVP
      solid-state basis set and obtain reasonable results for the X23 benchmark set and
      the potential energy curve for water adsorption on a nickel (110) surface.

PMID- 23947825
TI  - Chemical method for improving both the electrical conductivity and mechanical
      properties of carbon nanotube yarn via intramolecular cross-dehydrogenative
      coupling.
AB  - Chemical post-treatment of the carbon nanotube fiber (CNTF) was carried out via
      intramolecular cross-dehydrogenative coupling (ICDC) with FeCl3 at room
      temperature. The Raman intensity ratio of the G band to the D band (IG/ID ratio)
      of CNT fiber increased from 2.3 to 4.6 after ICDC reaction. From the XPS
      measurements, the AC?C/AC-C ratio of the CNT fiber increased from 3.6 to 4.8. It
      is of keen interest that both the electrical conductivity and tensile strength of
      CNT yarn improved to 3.5 * 10(3) S/cm and 420 MPa, which is 180 and 200% higher
      than that of neat CNT yarn. 

PMID- 23947826
TI  - Enantioselective effects of (+)- and (-)-citronellal on animal and plant
      microtubules.
AB  - Citronellal is a major component of Corymbia citriodora and Cymbopogon nardus
      essential oils. Herein it is shown that whereas (+)-citronellal (1) is an
      effective microtubule (MT)-disrupting compound, (-)-citronellal (2) is not.
      Quantitative image analysis of fibroblast cells treated with 1 showed total
      fluorescence associated with fibers resembling that in cells treated with the MT
      disrupting agents colchicine and vinblastine; in the presence of 2, the
      fluorescence more closely resembled that in control cells. The distribution of
      tubulin in soluble and insoluble fractions in the presence of 1 also resembled
      that in the presence of colchicine, whereas similar tubulin distribution was
      obtained in the presence of 2 and in control cells. In vitro polymerization of
      MTs was inhibited by 1 but not 2. Measurements of MT dynamics in plant cells
      showed similar MT elongation and shortening rates in control and 2-treated cells,
      whereas in the presence of 1, much fewer and shorter MTs were observed and no
      elongation or shrinkage was detected. Taken together, the MT system is suggested
      to be able to discriminate between different enantiomers of the same compound. In
      addition, the activity of essential oils rich in citronellal is affected by the
      relative content of the two enantiomers of this monoterpenoid. 

PMID- 23947827
TI  - Psychological investigation in patients with polycystic ovary syndrome.
AB  - BACKGROUND: The aim of the present study was to estimate the prevalence of mood
      disorders and examine a range of predictors for psychological well-being among
      Iranian women with polycystic ovary syndrome (PCOS). METHODS: A cross-sectional
      study was undertaken to ascertain the factors related to psychological distress
      in PCOS patients in Kashan, Iran. Psychological distress was measured using the
      Hospital Anxiety and Depression Scale (HADS). In addition we assessed quality of
      life using the Short Form Health Survey (SF-36). Socio-demographic details and
      clinical information of PCOS including obesity (body mass index), excessive body
      hair (hirsutism score), acne, menstrual cycle disturbances, infertility and
      endocrine profile also were recorded for each patient. RESULTS: In all 300 women
      with PCOS were entered into the study. Of these 32% (n =96) showed elevated HADS
      anxiety while depression was high in 5% (n =15). Quality of life was
      significantly impaired in women with anxiety (P <0.05), and depression (P <0.001)
      and in particular, in women with coexistence anxiety and depression (P <0.001)
      compared with unaffected participants. Compared with the non-depressed PCOS
      patients, the depressed women had significantly higher menstrual irregularities
      (P = 0.008). Moreover, we found significant difference in FAI level between the
      depressed and non depressed (p = 0.05), the anxious and non anxious patients (p <
      0.001) compare to non affected PCOS women. CONCLUSIONS: The high prevalence of
      depression and anxiety in this population suggests that initial evaluation of all
      women with PCOS should also include assessment of mental health disorders. The
      clinician should further pay attention to background of their patients especially
      in view of the factors influencing psychological well-being.

PMID- 23947829
TI  - Walter horl.

PMID- 23947828
TI  - Prognosis of rectal cancer patients improves with downstaging by intensified
      neoadjuvant radiochemotherapy - a matched pair analysis.
AB  - BACKGROUND: Neoadjuvant radiochemotherapy has been proven superior to adjuvant
      treatment in reducing the rate of local recurrence without impairing cancer
      related survival or the incidence of distant metastases in standard protocols of
      neoadjuvant radiochemotherapy. The present study aimed at addressing the effects
      of an intensified neoadjuvant radiochemotherapy on long term cancer related and
      disease free survival. METHODS: A total of 387 patients underwent oncologic
      resection for rectal cancer in our institution between January 2000 and December
      2009. There were 106 patients (27.4%) who received an intensified
      radiochemotherapy protocol completely and without excluding criteria (study
      group). A matched pair analysis was performed by comparing the study group with
      patients undergoing primary surgery and postoperative radiochemotherapy, if
      necessary and possible (control group). Matching was carried out in descending
      order for UICC stage, R-status, tumor height, T-, N-, V-, L-, M- and G-category
      of the TNM-system according to the histopathological staging. Follow-up data
      included local recurrence rate, cancer related and disease free survival.
      RESULTS: In the study group histopathological work-up of the specimen revealed a
      treatment response in terms of tumor regression in 92.5% (98/106) of these
      patients. Undergoing intensified neoadjuvant RCT the actuarial cancer related and
      disease free survival was 67.9% and 70.4%, local recurrence was 5.7% after an
      observation period of 4.3 +/- 2.55 years. In the control group cancer related and
      disease free survival was 71.7% and 82.7%, local recurrence was 4.7% after an
      observation period of 3.8 +/- 3.05 years revealing no statistical significant
      difference between the two groups. Moreover, estimated 5-year results of cancer
      related survival (66.7% vs 67.9% (controls)), the disease free survival (66.7% vs
      79.9% (controls)) as well as subgroup analysis of UICC 0-III and UICC IV patients
      showed no difference between the study and control group as well. CONCLUSION: In
      our study, intensified neoadjuvant radio-chemotherapy shows a high rate of tumor
      regression. The resulting inferior histopathological tumor stage shows the same
      long term local control and systemic tumor control as the control group with a
      primary more favorable tumor stage.

PMID- 23947830
TI  - Treatment of post-amputation pain with peripheral nerve stimulation.
AB  - BACKGROUND: Present treatment methods are often unsatisfactory in reducing post
      amputation pain. Peripheral nerve stimulation (PNS) could reduce the pain, but it
      is rarely used because present methods require invasive surgical access and
      precise placement of the leads in close proximity (<= 2 mm) with the nerve.
      METHODS: The present study investigated the feasibility of delivering PNS to
      patients with moderate-to-severe post-amputation pain in the lower extremity
      using a fine-wire lead placed percutaneously under ultrasound guidance a remote
      distance (0.5-3.0 cm) away from the sciatic and/or femoral nerves. RESULTS:
      Fourteen of the 16 subjects who completed in-clinic testing responded to
      stimulation, reported >= 75% paresthesia coverage, obtained clinically
      significant pain relief, and proceeded to a two-week home trial with a
      percutaneous PNS system. Two of the 14 responders had their leads removed early
      because of accidental dislodgement (N = 2), two had temporary discomfort near the
      lead (N = 2), and one had return of post-amputation pain despite stimulation (N =
      1) and did not complete the home trial. The nine responders who completed the
      home trial reported reductions in their mean daily worst post-amputation pain (56
      +/- 26%, 56 +/- 26%, N = 9), average residual limb pain (72 +/- 28%, 42 +/- 27%,
      N = 7), average phantom limb pain (81 +/- 28%, 47 +/- 48%, N = 7), residual limb
      pain interference (81 +/- 27%, 53 +/- 17%, N = 6), phantom limb pain interference
      (83 +/- 31%, 56 +/- 46%, N = 7), and Pain Disability Index (70 +/- 38%, 55 +/-
      32%, N = 9) during the second week of stimulation and four weeks after the end of
      stimulation, respectively. All nine responders rated their change in quality of
      life as improved at the end of stimulation and at the end of the four-week follow
      up period. Subjects reported minor decreases in the Beck Depression Inventory
      scores (43 +/- 51%, 32 +/- 57%, N = 9). Most subjects had no substantial changes
      other than minor decreases (N = 3) in pain medication. CONCLUSION: Achievement of
      significant pain relief and improvements in quality of life with a minimally
      invasive method of PNS holds promise for providing relief of post-amputation
      pain.

PMID- 23947833
TI  - Interaction of nonstructural protein 5A of the hepatitis C virus with Src
      homology 3 domains using noncanonical binding sites.
AB  - Src homology 3 (SH3) domains are widely known for their ability to interact with
      other proteins using the canonical PxxP binding motif. Besides those well
      characterized interaction modes, there is an increasing number of SH3 domain
      containing complexes that lack this motif. Here we characterize the interaction
      of SH3 domains, in particular the Bin1-SH3 domain, with the intrinsically
      disordered part of nonstructural protein 5A of the hepatitis C virus using
      noncanonical binding sites in addition to its PxxP motif. These binding regions
      partially overlap with regions that have previously been identified as having an
      increased propensity to form alpha-helices. Remarkably, upon interaction with the
      Bin1-SH3 domain, the alpha-helical propensity decreases and a fuzzy complex is
      formed. 

PMID- 23947834
TI  - Arsenic removal from contaminated water using three-dimensional graphene-carbon
      nanotube-iron oxide nanostructures.
AB  - We report a highly versatile and one-pot microwave route to the mass production
      of three-dimensional graphene-carbon nanotube-iron oxide nanostructures for the
      efficient removal of arsenic from contaminated water. The unique three
      dimensional nanostructure shows that carbon nanotubes are vertically standing on
      graphene sheets and iron oxide nanoparticles are decorated on both the graphene
      and the carbon nanotubes. The material with iron oxide nanoparticles shows
      excellent absorption for arsenic removal from contaminated water, due to its high
      surface-to-volume ratio and open pore network of the graphene-carbon nanotube
      iron oxide three-dimensional nanostructures. 

PMID- 23947835
TI  - Evidence for a multipotent mammary progenitor with pregnancy-specific activity.
AB  - INTRODUCTION: The mouse mammary gland provides a powerful model system for
      studying processes involved in epithelial tissue development. Although markers
      that enrich for mammary stem cells and progenitors have been identified, our
      understanding of the mammary developmental hierarchy remains incomplete. METHODS:
      We used the MMTV promoter linked to the reverse tetracycline transactivator to
      induce H2BGFP expression in the mouse mammary gland. Mammary epithelial cells
      (MECs) from virgin mice were sorted by flow cytometry for expression of the
      mammary stem cell/progenitor markers CD24 and CD29, and H2BGFP. Sorted
      populations were analyzed for in vivo repopulation ability, expression of mammary
      lineage markers, and differential gene expression. RESULTS: The reconstituting
      activity of CD24+/CD29+ cells in cleared fat pad transplantation assays was not
      distinguished in GFP+ compared to GFP- subpopulations. However, within the
      CD24+/CD29(lo) luminal progenitor-enriched population, H2BGFP+, but not H2BGFP-,
      MECs formed mammary structures in transplantation assays; moreover, this activity
      was dramatically enhanced in pregnant recipients. These outgrowths contained
      luminal and myoepithelial mammary lineages and produced milk, but lacked the
      capacity for serial transplantation. Transcriptional microarray analysis revealed
      that H2BGFP+/CD24+/CD29(lo) MECs are distinct from H2BGFP-/CD24+/CD29(lo) MECs
      and enriched for gene expression signatures with both the stem cell (CD24+/CD29+)
      and luminal progenitor (CD24+/CD29(lo)/CD61+) compartments. CONCLUSIONS: We have
      identified a population of MECs containing pregnancy-activated multipotent
      progenitors that are present in the virgin mammary gland and contribute to the
      expansion of the mammary gland during pregnancy.

PMID- 23947837
TI  - Computation of transit times using the milestoning method with applications to
      polymer translocation.
AB  - Milestoning is an efficient approximation for computing long-time kinetics and
      thermodynamics of large molecular systems, which are inaccessible to brute-force
      molecular dynamics simulations. A common use of milestoning is to compute the
      mean first passage time (MFPT) for a conformational transition of interest.
      However, the MFPT is not always the experimentally observed timescale. In
      particular, the duration of the transition path, or the mean transit time, can be
      measured in single-molecule experiments, such as studies of polymers
      translocating through pores and fluorescence resonance energy transfer studies of
      protein folding. Here we show how to use milestoning to compute transit times and
      illustrate our approach by applying it to the translocation of a polymer through
      a narrow pore. 

PMID- 23947838
TI  - Density functional theory for comprehensive orbital energy calculations.
AB  - This study reveals the reason core 1s orbital energies and the highest occupied
      molecular orbital (HOMO) energies of hydrogen and rare gas atoms are
      underestimated by long-range corrected (LC) density functional theory (DFT),
      which quantitatively reproduces the HOMO energies of other systems and the lowest
      unoccupied molecular orbital (LUMO) energies. Applying the pseudospectral
      regional (PR) self-interaction correction (SIC) drastically improved the
      underestimated orbital energies in LC-DFT calculations, while maintaining or
      improving the accuracies in the calculated valence HOMO and LUMO energies. This
      indicates that the self-interaction error in exchange functionals causes the
      underestimations of core 1s orbital energies and the HOMO energies of hydrogen
      and rare gas atoms in LC-DFT calculations. To clarify the reason for the
      improvement, the fractional occupation dependences of total electronic energies
      and orbital energies were examined. The calculated results clearly showed that
      the LC-PR functional gives almost linear dependences of total electronic energies
      for a slight decrease in the occupation number of core 1s orbitals, although this
      linear dependence disappears for significant decrease due to the shrinking of
      exchange self-interaction regions. It was also clarified that the PRSIC hardly
      affects the occupation number dependences of the total electronic energies and
      orbital energies for the fractional occupations of HOMOs and LUMOs. As a result,
      it was concluded that core orbital energies are obtained accurately by combining
      LC-DFT with PRSIC. 

PMID- 23947839
TI  - Decomposition-order effects of time integrator on ensemble averages for the Nose
      Hoover thermostat.
AB  - Decomposition-order dependence of time development integrator on ensemble
      averages for the Nose-Hoover dynamics is discussed. Six integrators were employed
      for comparison, which were extensions of the velocity-Verlet or position-Verlet
      algorithm. Molecular dynamics simulations by these integrators were performed for
      liquid-argon systems with several different time steps and system sizes. The
      obtained ensemble averages of temperature and potential energy were shifted from
      correct values depending on the integrators. These shifts increased in proportion
      to the square of the time step. Furthermore, the shifts could not be removed by
      increasing the number of argon atoms. We show the origin of these ensemble
      average shifts analytically. Our discussion can be applied not only to the liquid
      argon system but also to all MD simulations with the Nose-Hoover thermostat. Our
      recommended integrators among the six integrators are presented to obtain correct
      ensemble averages.

PMID- 23947840
TI  - Linear-scaling time-dependent density-functional theory in the linear response
      formalism.
AB  - We present an implementation of time-dependent density-functional theory (TDDFT)
      in the linear response formalism enabling the calculation of low energy optical
      absorption spectra for large molecules and nanostructures. The method avoids any
      explicit reference to canonical representations of either occupied or virtual
      Kohn-Sham states and thus achieves linear-scaling computational effort with
      system size. In contrast to conventional localised orbital formulations, where a
      single set of localised functions is used to span the occupied and unoccupied
      state manifold, we make use of two sets of in situ optimised localised orbitals,
      one for the occupied and one for the unoccupied space. This double representation
      approach avoids known problems of spanning the space of unoccupied Kohn-Sham
      states with a minimal set of localised orbitals optimised for the occupied space,
      while the in situ optimisation procedure allows for efficient calculations with a
      minimal number of functions. The method is applied to a number of medium sized
      organic molecules and a good agreement with traditional TDDFT methods is
      observed. Furthermore, linear scaling of computational cost with system size is
      demonstrated on (10,0) carbon nanotubes of different lengths. 

PMID- 23947841
TI  - Quantum mechanics/molecular mechanics dual Hamiltonian free energy perturbation.
AB  - The dual Hamiltonian free energy perturbation (DH-FEP) method is designed for
      accurate and efficient evaluation of the free energy profile of chemical
      reactions in quantum mechanical/molecular mechanical (QM/MM) calculations. In
      contrast to existing QM/MM FEP variants, the QM region is not kept frozen during
      sampling, but all degrees of freedom except for the reaction coordinate are
      sampled. In the DH-FEP scheme, the sampling is done by semiempirical QM/MM
      molecular dynamics (MD), while the perturbation energy differences are evaluated
      from high-level QM/MM single-point calculations at regular intervals, skipping a
      pre-defined number of MD sampling steps. After validating our method using an
      analytic model potential with an exactly known solution, we report a QM/MM DH-FEP
      study of the enzymatic reaction catalyzed by chorismate mutase. We suggest
      guidelines for QM/MM DH-FEP calculations and default values for the required
      computational parameters. In the case of chorismate mutase, we apply the DH-FEP
      approach in combination with a single one-dimensional reaction coordinate and
      with a two-dimensional collective coordinate (two individual distances), with
      superior results for the latter choice. 

PMID- 23947842
TI  - Redox reactions with empirical potentials: atomistic battery discharge
      simulations.
AB  - Batteries are pivotal components in overcoming some of today's greatest
      technological challenges. Yet to date there is no self-consistent atomistic
      description of a complete battery. We take first steps toward modeling of a
      battery as a whole microscopically. Our focus lies on phenomena occurring at the
      electrode-electrolyte interface which are not easily studied with other methods.
      We use the redox split-charge equilibration (redoxSQE) method that assigns a
      discrete ionization state to each atom. Along with exchanging partial charges
      across bonds, atoms can swap integer charges. With redoxSQE we study the
      discharge behavior of a nano-battery, and demonstrate that this reproduces the
      generic properties of a macroscopic battery qualitatively. Examples are the
      dependence of the battery's capacity on temperature and discharge rate, as well
      as performance degradation upon recharge. 

PMID- 23947843
TI  - Continuous time random walk with linear force applied to hydrated proteins.
AB  - An integro-differential diffusion equation with linear force, based on the
      continuous time random walk model, is considered. The equation generalizes the
      ordinary and fractional diffusion equations. Analytical expressions for
      transition probability density, mean square displacement, and intermediate
      scattering function are presented. The mean square displacement and intermediate
      scattering function can fit well the simulation data of the temperature-dependent
      translational dynamics of nitrogen atoms of elastin for a wide range of
      temperatures and various scattering vectors. Moreover, the numerical results are
      also compared with those of a fractional diffusion equation. 

PMID- 23947844
TI  - Modeling electron density distributions from X-ray diffraction to derive optical
      properties: constrained wavefunction versus multipole refinement.
AB  - The rational design of next-generation optical materials requires an
      understanding of the connection between molecular structure and the solid-state
      optical properties of a material. A fundamental challenge is to utilize the
      accurate structural information provided by X-ray diffraction to explain the
      properties of a crystal. For years, the multipole refinement has been the
      workhorse technique for transforming high-resolution X-ray diffraction datasets
      into the detailed electron density distribution of crystalline material. However,
      the electron density alone is not sufficient for a reliable calculation of the
      nonlinear optical properties of a material. Recently, the X-ray constrained
      wavefunction refinement has emerged as a viable alternative to the multipole
      refinement, offering several potential advantages, including the calculation of a
      wide range of physical properties and seeding the refinement process with a
      physically reasonable starting point. In this study, we apply both the multipole
      refinement and the X-ray constrained wavefunction technique to four molecules
      with promising nonlinear optical properties and diverse structural motifs. In
      general, both techniques obtain comparable figures of merit and generate largely
      similar electron densities, demonstrating the wide applicability of the X-ray
      constrained wavefunction method. However, there are some systematic differences
      between the electron densities generated by each technique. Importantly, we find
      that the electron density generated using the X-ray constrained wavefunction
      method is dependent on the exact location of the nuclei. The X-ray constrained
      wavefunction refinement makes smaller changes to the wavefunction when
      coordinates from the Hartree-Fock-based Hirshfeld atom refinement are employed
      rather than coordinates from the multipole refinement, suggesting that
      coordinates from the Hirshfeld atom refinement allow the X-ray constrained
      wavefunction method to produce more accurate wavefunctions. We then use the
      experimentally derived wavefunctions to calculate the molecular dipole moment,
      polarizability, hyperpolarizability, and refractive index and show that these are
      in good agreement with the values calculated using ab initio methods. Thus, this
      study shows that experimental wavefunctions can be reliably generated from X-ray
      diffraction datasets, and that optical properties can be reliably calculated from
      these wavefunctions. Such a concerted interplay of experiment and computation via
      the X-ray constrained wavefunction refinement stands to enable the molecular
      engineering of tailor-made next-generation optical materials. 

PMID- 23947845
TI  - Effective tight-binding models for excitons in branched conjugated molecules.
AB  - Effective tight-binding models have been introduced to describe vertical
      electronic excitations in branched conjugated molecules. The excited-state
      electronic structure is characterized by quantum particles (excitons) that reside
      on an irregular lattice (graph) that reflects the molecular structure. The
      methodology allows for the exciton spectra and energy-dependent exciton
      scattering matrices to be described in terms of a small number of lattice
      parameters which can be obtained from quantum-chemical computations using the
      exciton scattering approach as a tool. We illustrate the tight-binding model
      approach using the time-dependent Hartree-Fock computations in phenylacetylene
      oligomers. The on-site energies and hopping constants have been identified from
      the exciton dispersion and scattering matrices. In particular, resonant, as well
      as bound states, are reproduced for a symmetric quadruple branching center. The
      capability of the tight-binding model approach to describe the exciton-phonon
      coupling and energetic disorder in large branched conjugated molecules is briefly
      discussed. 

PMID- 23947846
TI  - Understanding wetting of immiscible liquids near a solid surface using molecular
      simulation.
AB  - We introduce Monte Carlo simulation methods for determining interfacial
      properties of fluids that exhibit bulk liquid-liquid immiscibility. An interface
      potential-based approach, in which the interfacial properties of a system are
      related to the surface excess free energy of a thin fluid film in contact with a
      surface, is utilized to deduce the wetting characteristics of these systems. We
      present a framework for implementing this general method within both the grand
      canonical and semigrand isobaric-isothermal ensembles. Tracking the evolution of
      interfacial properties along various thermodynamic paths is also examined. This
      task is accomplished by implementing variants of the expanded ensemble technique,
      which enables one to obtain components of the interface potential along a path of
      interest. We also discuss how these concepts are employed to calculate bulk
      liquid-liquid coexistence properties in an efficient manner. The computational
      strategies introduced here are applied to three model Lennard-Jones systems. For
      each system, we compile the evolution of the liquid-liquid surface tension and
      contact angle with temperature or pressure. For one of the model systems we
      compare our results with literature data. We also examine how interfacial
      properties evolve upon variation of the relative affinity of the fluid components
      for the substrate. Overall, we find that the approach pursued here is generally
      applicable and provides an efficient and precise means to calculate the bulk and
      interfacial properties of fluids that exhibit liquid-liquid immiscibility. 

PMID- 23947847
TI  - Interpair electron correlation by second-order perturbative corrections to PNOF5.
AB  - An antisymmetrized product of strongly orthogonal geminals with the expansion
      coefficients explicitly expressed by the occupation numbers is used to generate
      the Piris natural orbital functional 5 (PNOF5). Second-order corrections to PNOF5
      are derived and implemented using the multiconfigurational perturbation theory
      size consistent at second-order (SC2-MCPT). A modified version of the SC2-MCPT
      including only doubly excited determinants from different geminals is proposed to
      describe the dispersion interaction in the helium dimer, and to avoid the
      breakdown of curves in homolytic dissociations of FH, CO, and N2. Comparisons of
      calculated properties to experimental data are included to verify the accuracy of
      the formulation. 

PMID- 23947848
TI  - Study of interatomic Coulombic decay of Ne(H2O)n (n = 1,3) clusters using
      equation-of-motion coupled-cluster method.
AB  - Interatomic Coulombic decay (ICD) is an efficient and ultrafast radiationless
      decay mechanism which can be initiated by removal of an electron from the inner
      valence shell of an atom or molecule. Generally, the ICD mechanism is prevailed
      in weakly bound clusters. A very promising approach, known as CAP/EOM-CC,
      consists of the combination of complex absorbing potential (CAP) with the
      equation-of-motion coupled-cluster (EOM-CC) method, is applied for the first time
      to study the nature of the ICD mechanism. We have applied this technique to
      determine the lifetime of an auto-ionized, inner-valence excited state of the
      NeH2O, Ne(H2O)2, and Ne(H2O)3 systems. The lifetime is found to be very short and
      decreases significantly with the number of neighboring water molecules. 

PMID- 23947849
TI  - Theoretical characterization of C7, C7-, and C7+.
AB  - We present a theoretical investigation of neutral and ionic C7 molecules. Since
      carbon chains present isomerism and the number of possible structures increases
      fast with the number of carbon atoms, a B3LYP/aug-cc-pVTZ search of stationary
      points has been achieved. For C7, we found twelve minimal structures. Among these
      forms, eleven C7 isomers are located into the lowest singlet hyper potential
      energy surface. The most stable form of C7 is linear and possesses a (1)Sigmag(+)
      symmetry species. For C7(-), we characterized fifteen stable forms, where twelve
      are of doublet spin-multiplicity. The global minimum of C7(-) is a (2)Pig doubly
      degenerate Renner-Teller structure. For C7(+) cation, we found eleven doublet and
      three quartet isomers with a 7-atom cycle, C7(+) (X(2)A1) ground state. For the
      most stable forms, explicitly correlated (R)CCSD(T)-F12 calculations have been
      performed for the determination of equilibrium geometries and for the
      spectroscopic characterization of C7, C7(-), and C7(+), providing accurate
      rotational constants and harmonic frequencies. Vertical excitation energies to
      the lowest electronic states have been computed at the CASSCF/MRCI/aug-cc-pVTZ
      level. Thirty five electronic states of C7, suitable of being involved in
      reactive processes, lie below 7 eV. Fourteen metastable electronic states of C7(
      ) have been found below 3.5 eV. For linear-C7, we compute the electron affinity
      and the ionization energy to be 3.38 eV and 10.42 eV, respectively.

PMID- 23947850
TI  - Tunneling splittings in vibronic energy levels of CH3F+ (X2E) studied by high
      resolution photoelectron spectroscopy and ab initio calculation.
AB  - The energy levels of CH3F(+) (X(2)E), which show strong vibronic coupling effect
      (Jahn-Teller effect), have been measured up to 3500 cm(-1) above the ground
      vibrational state using one-photon zero-kinetic energy photoelectron
      spectroscopic method. Theoretical calculations have also been performed to
      calculate the spin-vibronic energy levels using a diabatic model and ab initio
      adiabatic potential energy surfaces (APESs) including the energy gradients and
      derivative couplings between the APESs. The calculations showed that the
      tunneling splittings of the vibrational energy levels occur due to the deep
      potential energy wells formed by the Jahn-Teller deformation. The calculated spin
      vibronic energy levels are in good agreement with the experimental data. For
      example, the energy splitting for the first excited vibrational energy level is
      calculated as 111 cm(-1) that is confirmed by the experimental value. The
      experimental spectrum was assigned based on the fundamental vibrational modes
      calculated at the energy minimum. The fundamental vibrational modes related to
      the H-C-F bending, H-C-H bending, C-F stretching, and C-H stretching vibrations
      have been observed.

PMID- 23947851
TI  - Excited states of aniline by photoabsorption spectroscopy in the 30,000-90,000
      cm(-1) region using synchrotron radiation.
AB  - The photoabsorption spectrum of aniline (C6H5NH2) in gas phase in the 30,000
      90,000 cm(-1) (3.7-11.2 eV) region is recorded at resolution limit of 0.008 eV
      using synchrotron radiation source for the first time to comprehend the nature of
      the excited valence and Rydberg states. The first half of the energy interval
      constitutes the richly structured valence transitions from the ground to excited
      states up to the first ionization potential (IP) at 8.02 eV. The spectrum in the
      second half consists of vibrational features up to second IP (9.12 eV) and
      structureless broad continuum up to the third IP (10.78 eV). The electronic
      states are assigned mainly to the singlets belonging to pi -> pi* transitions. A
      few weak initial members of Rydberg states arising from pi -> 4s, np or nd
      transitions are also identified. Observed vibrational features are assigned to
      transitions from the ground state A' to the excited states 1A", 3A', 5A", 6A',
      and 10A" in C(s) symmetry. Time dependent density functional theory (TDDFT)
      calculations at B3LYP level of theory are employed to obtain the vertical
      excitation energies and the symmetries of the excited states in equilibrium
      configuration. The computed values of the transition energies agree fairly well
      with the experimental data. Further the calculated oscillator strengths are used
      to substantiate the assignments of the bands. The work provides a comprehensive
      picture of the vacuum ultraviolet photoabsorption spectrum of aniline up to its
      third ionization limit.

PMID- 23947852
TI  - A generic pi* shape resonance observed in energy-dependent photoelectron angular
      distributions from two-colour, resonant multiphoton ionization of difluorobenzene
      isomers.
AB  - We present new evidence for the existence of a near threshold pi* shape resonance
      as a common feature in the photoionization of each isomer of difluorobenzene.
      Experimentally, this is revealed by significant changes in the anisotropy of the
      photoelectron angular distributions (PADs) following the ionization of the
      optically aligned S1 state of these molecules at varying photon energies.
      Continuum multiple scattering Xalpha calculations reproduce this behaviour well,
      and allow the visualisation of the continuum shape resonances. The resonances are
      unusually narrow in energy (<1 eV), but nevertheless appear to extend right down
      to the ionization thresholds--exactly the low energy range typically accessed in
      laser-based resonance enhanced multiphoton ionization (REMPI) schemes. The
      anticipation of such pronounced energy dependence in the PADs and cross-sections
      sought for other molecules, and an ability to accurately predict such features,
      should be important for the reliable application and interpretation of
      experiments involving REMPI probing of those molecules.

PMID- 23947853
TI  - Equilibrium configuration of the 1u state of hydrogen molecular ion in a magnetic
      field.
AB  - Using the variational method based on the Gaussian basis set, the authors
      investigate the 1u state of hydrogen molecular ion in a non-parallel magnetic
      field with respect to the fixed molecular axis. At sufficiently small field
      strength, the equilibrium configuration prefers the perpendicular orientation, in
      which the (relative) orientation theta between the magnetic field and the
      molecular axis is 90 degrees . With increasing field strength, the orientation
      theta of the equilibrium configuration decreases, and is neither the parallel
      orientation nor the perpendicular orientation at field strength between 10(9) G
      and 2.35 * 10(10) G. Meanwhile, more and more configurations with large
      orientations become unstable with respect to the dissociation H + p.

PMID- 23947854
TI  - Unusually large spin polarization and magnetoresistance in a FeMg8-FeMg8
      superatomic dimer.
AB  - Electronic transport across a FeMg8 magnetic superatom and its dimer has been
      investigated using a density functional theory combined with Keldysh
      nonequilibrium Green's-function formalism. For a single cluster, our studies for
      the cluster supported in various orientations on a Au(100) surface show that the
      transport is sensitive to the contact geometry. Investigations covering the cases
      where the axes of Mg square antiprism are 45 degrees , perpendicular, and
      parallel to the transport direction, show that the equilibrium conductance,
      transferred charge, and current polarizations can all change significantly with
      orientation. Our studies on the transport across a magnetic superatom dimer FeMg8
      FeMg8 focus on the effect of electrode contact distance and the support. The
      calculated I-V curves show negative differential resistance behavior at larger
      electrode-cluster contact distances. Further, the equilibrium conductance in
      ferromagnetic state shows an unusually high spin polarization that is about
      81.48% for specific contact distance, and a large magnetoresistance ratio
      exceeding 500% is also found. The results show that the superatom assemblies can
      provide unusual transport characteristics, and that the spin polarization and
      magnetoresistance can be controlled via the contact geometry. 

PMID- 23947855
TI  - A Chebyshev method for state-to-state reactive scattering using reactant-product
      decoupling: OH + H2 -> H2O + H.
AB  - We extend a recently developed wave packet method for computing the state-to
      state quantum dynamics of AB + CD -> ABC + D reactions [M. T. Cvitas and S. C.
      Althorpe, J. Phys. Chem. A 113, 4557 (2009)] to include the Chebyshev propagator.
      The method uses the further partitioned approach to reactant-product decoupling,
      which uses artificial decoupling potentials to partition the coordinate space of
      the reaction into separate reactant, product, and transition-state regions.
      Separate coordinates and basis sets can then be used that are best adapted to
      each region. We derive improved Chebyshev partitioning formulas which include
      Mandelshtam-and-Taylor-type decoupling potentials, and which are essential for
      the non-unitary discrete variable representations that must be used in 4-atom
      reactive scattering calculations. Numerical tests on the fully dimensional OH +
      H2 -> H2O + H reaction for J = 0 show that the new version of the method is as
      efficient as the previously developed split-operator version. The advantages of
      the Chebyshev propagator (most notably the ease of parallelization for J > 0) can
      now be fully exploited in state-to-state reactive scattering calculations on 4
      atom reactions. 

PMID- 23947856
TI  - The vibrational bound states of isomerising disilyne.
AB  - Full-dimensional variational calculations are reported for the isomerising
      disilyne molecule, Si2H2. Large-scale calculations using coordinates based on
      orthogonal satellite vectors permitted the computation of excited vibrational
      state energies and wavefunctions for all four isomeric forms: dibridged Si(H2)Si,
      monobridged Si(H)SiH, disilavinylidene H2SiSi, and trans-bent HSiSiH. Energies
      and wavefunctions have been determined for the lowest 2400 totally symmetric
      vibrational states; this set includes highly excited states above all three
      chemically relevant isomerisation barriers--up to about 8300 cm(-1) above the
      (dibridged) ground state. States strongly localised in the dibridged,
      monobridged, and disilavinylidene regions of the potential energy surface have
      been found as well as many partially or fully delocalised states. For the trans
      bent form, only partially localised states have been identified. Comparisons are
      made with similar literature calculations on the isovalent acetylene-vinylidene
      system HCCH/H2CC.

PMID- 23947857
TI  - Inelastic neutron scattering spectrum of H2@C60 and its temperature dependence
      decoded using rigorous quantum calculations and a new selection rule.
AB  - In the supramolecular complex H2@C60, the lightest of molecules, H2, is
      encapsulated inside the most highly symmetric molecule C60. The elegance and
      apparent simplicity of H2@C60 conceal highly intricate quantum dynamics of the
      coupled translational and rotational motions of the guest molecule in a nearly
      spherical nanoscale cavity, which embodies some of the most fundamental concepts
      of quantum mechanics. Here we present the first rigorous and highly accurate
      quantum calculations of the inelastic neutron scattering (INS) spectra of this
      prototypical endohedral fullerene complex and their temperature dependence. The
      calculations enable complete assignment of the recently reported experimental INS
      spectra of H2@C60 measured at several temperatures. We also derive a new and
      unexpected selection rule for the INS spectroscopy of H2 in a near-spherical
      confinement, which explains why the INS transitions between certain translation
      rotation eigenstates of H2 in C60 have zero intensity and do not appear in the
      spectra. 

PMID- 23947858
TI  - Plasmon hybridization model generalized to conductively bridged nanoparticle
      dimers.
AB  - Charge transfer introduced by a conductive junction bridging a nanoparticle dimer
      can have a pronounced effect on the optical properties of the system. We have
      extended the plasmon hybridization model to include conductive junctions and
      charge transfer effects. From our model, we are able to derive all the plasmon
      resonances of the bridged dimer, including the charge transfer plasmon (CTP), and
      predict their trends when system parameters are varied. In particular, we find
      that CTP is a result of a sufficiently narrow monopole mode interacting with
      multipolar (including dipolar) modes. The screening arising from charge transfer
      induces a blueshift of the hybridized bonding dimer modes and decreases the
      electric field in the junction. Our model may serve as an important guide for
      optical properties of bridged nanoparticle aggregates. 

PMID- 23947859
TI  - Dynamics of the C/H and C/F exchanges in the reaction of 3P carbon atoms with
      vinyl fluoride.
AB  - Two product channels C3H2F + H and C3H3 + F were identified in the reaction of
      C((3)P) atoms with vinyl fluoride (C2H3F) at collision energy 3.7 kcal mol(-1) in
      a crossed molecular-beam apparatus using selective photoionization. Time-of
      flight (TOF) spectra of products C3H2F and C3H3 were measured at 12-16 laboratory
      angles as well as a TOF spectrum of atomic F, a counter part of C3H3, was
      recorded at single laboratory angle. From the best simulation of product TOF
      spectra, translational-energy distributions at seven scattering angles and a
      nearly isotropic (forward and backward peaked) angular distribution were
      derivable for exit channel C3H2F + H (C3H3 + F) that has average kinetic-energy
      release of 14.5 (4.9) kcal mol(-1). Products C3H2F + H and C3H3 + F were
      estimated to have a branching ratio of ~53:47. Furthermore, TOF spectra and
      photoionization spectra of products C3H2F and C3H3 were measured at laboratory
      angle 62 degrees  with photoionization energy ranging from 7 eV to 11.6 eV. The
      appearance of TOF spectra is insensitive to photon energy, implying that only
      single species overwhelmingly contributes to products C3H2F and C3H3. HCCCHF
      (H2CCCH) was identified as the dominant species based on the measured ionization
      threshold of 8.3 +/- 0.2 (8.6 +/- 0.2) eV and the maximal translational-energy
      release. The C/H and C/F exchange mechanisms are stated.

PMID- 23947860
TI  - A theoretical study of hydrated molecular clusters of amines and dicarboxylic
      acids.
AB  - Amines and carboxylic acids have been recognized as important precursor species
      in atmospheric new particle formation. In this study, the interaction between
      dimethylamine and succinic acid is investigated using Basin Paving Monte Carlo
      (BPMC) sampling with the classical force field to obtain low energy conformers of
      dimethylamine and succinic acid hydrated molecular clusters. Geometry
      optimization and frequency calculations are further performed on the basis of the
      BPMC results using density functional theory. At standard temperature and
      pressure, dimethylamine binds to succinic acid with a bonding energy of 14.2 kcal
      mol(-1), smaller than that of dimethylamine with sulfuric acid (21.1 kcal mol(
      1)). Hydration promotes proton transfer from succinic acid to dimethylamine and
      consequently increases the interaction strength, while proton transfer from
      sulfuric acid to dimethylamine occurs without hydration. On the other hand, the
      reactivity of sulfuric acid with dimethylamine decreases with the degree of
      hydration of sulfuric acid. The free energies of formation for hydrated clusters
      consisting of dimethylamine and succinic acid reveal that the interaction between
      amines and dicarboxylic acids likely exerts a synergetic effect on atmospheric
      aerosol nucleation by formation of aminium carboxylate ion pairs.

PMID- 23947861
TI  - Coupled cluster calculations on TiO2 nanoclusters.
AB  - The excitation energies of the four lowest-lying singlet excited states of the
      TiO2, Ti2O4, and Ti3O6 clusters are calculated by a variety of different Equation
      of-Motion Coupled Cluster (EOM-CC) approaches in order to obtain benchmark values
      for the optical excitations of titanium dioxide clusters. More specifically we
      investigate what the effect is of the inclusion of triple excitations "triples"
      in the (EOM-)CC scheme on the calculated excited states of the clusters. While
      for the monomer and dimer the inclusion of triples is found to only cause a rigid
      shift in the excitation energies, in the case of the trimer the crossing of the
      excited states is observed. Coupled cluster approaches where triples are treated
      perturbatively were found to offer no advantage over EOM-CCSD, whereas the active
      space methods (EOM-CCSDt(II/I)) were demonstrated to yield results very close to
      full EOM-CCSDT, but at a much reduced computational cost.

PMID- 23947862
TI  - On the mechanism for the nonadiabatic reactive quenching of OH(A2Sigma+) by
      H2(1Sigmag+): the role of the 2(2)A state.
AB  - A scheme for reactive electronic quenching of OH(A(2)Sigma(+)) through collisions
      with H2 is proposed, supported by electronic structure data obtained from
      multireference configuration interaction wave functions. The scheme represents an
      insertion pathway that leads from the initial 3(2)A state in the reactant
      channel, into a valence region, where a nonadiabatic transition to the 2(2)A
      state, enabled by a 2(2)A-3(2)A conical intersection seam occurs. Once on the
      2(2)A state, insertion of HO into H2 provides access to a linking region and,
      after surmounting a small barrier, to a region where the low-lying electronic
      states are Rydberg in character, corresponding to the 3s, 3p(x), 3p(y), and 3p(z)
      states of OH3(+). In the Rydberg region, a deep well on the 2(2)A potential
      energy surface exists. Direct passage from the 2(2)A state to ground state
      products, H2O(X(1)A1) + H, is precluded by an energy barrier so that an
      intermediate complex can be formed on the 2(2)A potential energy surface. As the
      insertion is facilitated by rehybridization of the oxygen orbitals from sp to
      sp(3) in the linking region, nonplanar approach of HO to H2 is favored. The
      precipitous change in electronic structure from valence to Rydberg character
      renders the linking region inaccessible on the 3(2)A potential energy surface.
      From the 2(2)A state in the Rydberg region, access to the H2O + H product channel
      is enabled by repeated passage through a region of appreciable 1(2)A-2(2)A
      derivative coupling or by radiative decay. This scheme supplements other pathways
      in which nonadiabatic transitions from the 2(2)A state to the 1(2)A state in the
      valence region enable both planar and nonplanar insertion and abstraction paths
      leading directly to H2O products.

PMID- 23947863
TI  - Photofragmentation dynamics of ICN(-)(CO2)n clusters following visible
      excitation.
AB  - Photodissociation of ICN(-)(CO2)n, n = 0-18, with 500-nm excitation is
      investigated using a dual time-of-flight mass spectrometer. Photoabsorption to
      the (2)Pi(1/2) state is detected using ionic-photoproduct action spectroscopy;
      the maximum absorption occurs around 490 nm. Ionic-photoproduct distributions
      were determined for ICN(-)(CO2)n at 500 nm. Following photodissociation of bare
      ICN(-) via 430-650 nm excitation, a small fraction of CN(-) is produced,
      suggesting that nonadiabatic effects play a role in the photodissociation of this
      simple anion. Electronic structure calculations, carried out at the MR-SO-CISD
      level of theory, were used to evaluate the potential-energy surfaces for the
      ground and excited states of ICN(-). Analysis of the electronic structure
      supports the presence of nonadiabatic effects in the photodissociation dynamics.
      For n >= 2, the major ionic photoproduct has a mass corresponding to either
      partially solvated CN(-) or partially solvated [NCCO2](-).

PMID- 23947864
TI  - Charge transport in organic semiconductors: assessment of the mean field theory
      in the hopping regime.
AB  - The performance of the mean field theory to account for charge transfer rate in
      molecular dimers and charge transport mobility in molecular stacks with small
      intermolecular electronic coupling and large local electron-phonon coupling
      (i.e., in the hopping regime) is carefully investigated against various other
      approaches. Using Marcus formula as a reference, it is found that mean field
      theory with system-bath interaction and surface hopping approaches yield fully
      consistent charge transfer rates in dimers. However, in contrast to the dimer
      case, incorporating system-bath interaction in the mean field approach results in
      a completely wrong temperature dependence of charge carrier mobility in larger
      aggregates. Although the mean field simulation starting from the relaxed geometry
      of a charged molecule and neglecting system-bath interaction can reproduce
      thermally activated transport, it is not able to characterize properly the role
      of additional nonlocal electron-phonon couplings. Our study reveals that the mean
      field theory must be used with caution when studying charge transport in the
      hopping regime of organic semiconductors, where the surface hopping approach is
      generally superior. 

PMID- 23947865
TI  - How do high pressures change the Debye process of 4-methyl-3-heptanol?
AB  - 4-methyl-3-heptanol, a monohydroxy alcohol with a relatively small dielectric
      Debye process, is studied in wide ranges of temperature (143 K < T < 308 K) and
      pressure (0.1 MPa < p < 864 MPa). When monitored under isochronous conditions,
      i.e., focusing on constant relaxation times, as well as under isothermal
      conditions, the Debye process gains significant intensity upon pressure
      application. This behavior contrasts with that of the previously studied octanol
      2-ethyl-1-hexanol, which features a large Debye process. These experimentally
      observed, clearly distinguishable pressure evolutions are discussed to reflect
      differences in the formation of hydrogen-bonded supramolecular structures. 

PMID- 23947866
TI  - Density and anomalous thermal expansion of deeply cooled water confined in
      mesoporous silica investigated by synchrotron X-ray diffraction.
AB  - A synchrotron X-ray diffraction method was used to measure the average density of
      water (H2O) confined in mesoporous silica materials MCM-41-S-15 and MCM-41-S-24.
      The average density versus temperature at atmospheric pressure of deeply cooled
      water is obtained by monitoring the intensity change of the MCM-41-S Bragg peaks,
      which is directly related to the scattering length density contrast between the
      silica matrix and the confined water. Within MCM-41-S-15, the pore size is small
      enough to prevent the crystallization at least down to 130 K. Besides the well
      known density maximum at 277 K, a density minimum is observed at 200 K for the
      confined water, below which a regular thermal expansion behavior is restored.
      Within MCM-41-S-24 of larger pore size, water freezes at 220.5 K. The average
      water/ice density measurement in MCM-41-S-24 validated the diffraction method.
      The anomalous thermal expansion coefficient (alphap) is calculated. The
      temperature at which the alphap reaches maximum is found to be pore size
      independent, but the peak height of the alphap maximum is linearly dependent on
      the pore size. The obtained data are critical to verify available theoretical and
      computational models of water.

PMID- 23947867
TI  - Molecular dynamics study of network statistics in lithium disilicate: Q(n)
      distribution and the pressure-volume diagram.
AB  - Molecular dynamics simulations have been performed to study the structures along
      the pressure-volume diagram of network-glasses and melts exemplified by the
      lithium disilicate system. Experimentally, densification of the disilicate glass
      by elevated pressure is known and this feature is reasonably reproduced by the
      simulations. During the process of densification or decompression of the system,
      the statistics of Q(n) (i.e., SiO4 tetrahedron unit with n bridging oxygen linked
      to the silicon atom where n = 0, 1, 2, 3, or 4) change, and the percentage of the
      Q3 structures show the maximum value near atmospheric pressure at around T(g).
      Changes of Q(n) distribution are driven by the changes of volume (or pressure)
      and are explained by the different volumes of structural units. Furthermore, some
      pairs of network structures with equi-volume, but having different distributions
      of Q(n) (or different heterogeneity), are found. Therefore, for molecular
      dynamics simulations of the Q(n) distributions, it is important to take into
      account the complex phase behavior including poly-structures with different
      heterogeneities as well as the position of the system in the P-V-T diagram.

PMID- 23947868
TI  - Excess volume and heat of mixing in Cu-Ti liquid mixture.
AB  - Molar excess volume of Cu-Ti liquid mixture has been investigated to elucidate
      how the excess volume in binary alloys is related to mixing enthalpy and
      microscopic interactions. Cu-Ti is used as a key example for systems showing
      positive excess volume and negative mixing enthalpy. For this purpose, the
      density of several Cu-Ti binary mixtures has been measured over the whole
      composition range by the containerless technique of electromagnetic levitation as
      a function of temperature. A linear temperature dependence of the density has
      been found for all investigated alloys. In addition, the density decreases with
      increasing Ti content in the alloys, showing a negative deviation from the ideal
      solution model. As mentioned, a positive excess volume was found whereas the
      enthalpy of mixing is negative. This behavior has been discussed in relation with
      chemical ordering and the role played by attractive and repulsive interactions in
      the system, according to previous results obtained by means of molecular dynamics
      simulation on binary dense fluids. 

PMID- 23947869
TI  - Simulation of transport around the coexistence region of a binary fluid.
AB  - We use Monte Carlo and molecular dynamics simulations to study phase behavior and
      transport properties in a symmetric binary fluid where particles interact via
      Lennard-Jones potential. Our results for the critical behavior of collective
      transport properties, with particular emphasis on bulk viscosity, is understood
      via appropriate application of finite-size scaling technique. It appears that the
      critical enhancements in these quantities are visible far above the critical
      point. This result is consistent with an earlier report from computer simulations
      where, however, the authors do not quantify the critical singularity. 

PMID- 23947870
TI  - Poisson ratio and excess low-frequency vibrational states in glasses.
AB  - In glass, starting from a dependence of the Angell's fragility on the Poisson
      ratio [V. N. Novikov and A. P. Sokolov, Nature 431, 961 (2004)], and a dependence
      of the Poisson ratio on the atomic packing density [G. N. Greaves, A. L. Greer,
      R. S. Lakes, and T. Rouxel, Nature Mater. 10, 823 (2011)], we propose that the
      heterogeneities are predominantly density fluctuations in strong glasses (lower
      Poisson ratio) and shear elasticity fluctuations in fragile glasses (higher
      Poisson ratio). Because the excess of low-frequency vibration modes in comparison
      with the Debye regime (boson peak) is strongly connected to these fluctuations,
      we propose that they are breathing-like (with change of volume) in strong glasses
      and shear-like (without change of volume) in fragile glasses. As a verification,
      it is confirmed that the excess modes in the strong silica glass are
      predominantly breathing-like. Moreover, it is shown that the excess breathing
      like modes in a strong polymeric glass are replaced by shear-like modes under
      hydrostatic pressure as the glass becomes more compact. 

PMID- 23947871
TI  - On the state of water in 2.4 nm cylindrical pores of MCM from dynamic and normal
      specific heat studies.
AB  - Relaxation phenomenon, thermodynamics, and phase transformation of water in
      nanopores has been studied by differential scanning calorimetry, usually on
      heating a precooled sample. Interpretation of such results is ambiguous, because
      the data do not indicate whether or not there is a thermal hysteresis between the
      heating and cooling paths. We argue that measurements on both the cooling and
      heating paths are needed, particularly for complex systems, and also measurements
      of the complex quantity are needed to ascertain that the Kramers-Kronig relations
      for a relaxation process are obeyed. We report a study of the real and imaginary
      components of the complex specific heat, C(p)' and C(p)", and the time-dependent
      C(p,app) of water confined to 2.4 nm diameter cylindrical pores on both the
      cooling and heating paths, and use different thermal histories. C(p,app) of
      nanoconfined water shows two exothermic peaks during cooling below 255 K at 12
      K/h and only one endothermic peak on heating, and the enthalpy change determined
      from the exotherm is more than that determined from the endotherm. C(p,app) and
      C(p)' of the partially crystallized water is higher at 240 K than at 275 K on the
      cooling path, and C(p,app) and C(p)' of the partially crystalline water are lower
      at 240 K than at 275 K on the heating path, thus showing a thermal hysteresis in
      this range. Studies by using 60 K/h cooling and heating rates and the effect of
      heat treatment at selected temperatures confirm that the features observed are
      due to slow crystallization and slow melting. The endotherm observed on the
      heating path with onset at 220 K and peak at 227 K is due to gradual melting of
      the ice in nanopores, and not due to glass-softening transition, a liquid-liquid
      transition, or an approach toward the conjectured critical point of the
      supercooled water in the 2.4 nm pores.

PMID- 23947872
TI  - On the cooperative nature of the beta-process in neat and binary glasses: a
      dielectric and nuclear magnetic resonance spectroscopy study.
AB  - By means of dielectric as well as (2)H and (31)P nuclear magnetic resonance
      spectroscopy (NMR) the component dynamics of the binary glass tripropyl phosphate
      (TPP)/polystyrene (PS/PS-d3) is selectively investigated for concentrations
      distributed over the full range. We study the secondary (beta-) relaxation below
      T(g), which is found in all investigated samples containing TPP, but not in neat
      polystyrene. The dielectric spectrum of the beta-process is described by an
      asymmetric distribution of activation energies, essentially not changing in the
      entire concentration regime; its most probable value is E/k ? 24 T(g).
      Persistence of the beta-process is confirmed by (31)P NMR Hahn-echo and spin
      lattice relaxation experiments on TPP, which identify the nature of the beta
      process as being highly spatially hindered as found for other (neat) glasses
      studied previously, or re-investigated within this work. The corresponding (2)H
      NMR experiments on PS-d3 confirm the absence of a beta-process in neat PS-d3, but
      reveal a clear signature of a beta-process in the mixture, i.e., polystyrene
      monomers perform essentially the same type of secondary relaxation as the TPP
      molecules. Yet, there are indications that some fractions of PS-d3 as well as TPP
      molecules become immobilized in the mixture in contrast to the case of neat
      glasses. We conclude that in a binary glass the beta-process introduced by one
      component induces a highly similar motion in the second component, and this may
      be taken as an indication of its cooperative nature.

PMID- 23947873
TI  - Site-site direct correlation functions for three popular molecular models of
      liquid water.
AB  - Direct correlation functions (DCFs) play a pivotal role in the applications of
      classical density functional theory (DFT) to addressing the thermodynamic
      properties of inhomogeneous systems beyond the local-density or mean-field
      approximations. Whereas numerous studies have been dedicated to the radial
      distribution functions of liquid water--the most important solvent on earth,
      relatively little attention has been given to the site-site DCFs. The water DCFs
      are long-ranged and difficult to calculate directly by simulation, and the
      predictions from conventional liquid-state theories have been rarely calibrated.
      Here we report a computational procedure for accurate evaluation of the site-site
      DCFs of liquid water based on three popular molecular models (viz., SPC, SPC/E,
      and TIP3P). The numerical results provide a benchmark for calibration of
      conventional liquid-state theories and fresh insights into development of new DFT
      methods. We show that: (1) the long-range behavior of the site-site DCFs depends
      on both the molecular model and the thermodynamic condition; (2) the asymptotic
      limit of DCFs at large distance does not follow the mean-spherical approximation
      (MSA); (3) individual site-site DCFs are long ranged (~40 nm) but a summation of
      all DCF pairs exhibits only short-range behavior (~1 nm or a few water
      diameters); (4) the site-site bridge correlation functions behave as the DCFs,
      i.e., they are also long-ranged while the summation of all bridge correlation
      functions is short ranged. Our analytical and numerical analyses of the DCFs
      provide some simple strategies for possible improvement of the numerical
      performance of conventional liquid-state theories.

PMID- 23947874
TI  - Description of fluid dynamics and coupled transports in models of a laminar flow
      diffusion chamber.
AB  - The aim of this study is to assess how much the results of nucleation experiments
      in a laminar flow diffusion chamber (LFDC) are influenced by the complexity of
      the model of the transport properties. The effects of the type of fluid dynamic
      model (the steady state compressible Navier-Stokes system for an ideal
      gas/parabolic profile approximation) and the contributions of the coupled terms
      describing the Dufour effects and thermodiffusion on the predicted magnitude of
      the nucleation maxima and its location were investigated. This study was
      performed on the model of the homogeneous nucleation of an n-butanol-He vapor
      mixture in a LFDC. The isothermal dependencies of the nucleation rate on
      supersaturation were determined at three nucleation temperatures: 265 K, 270 K,
      and 280 K. For this purpose, the experimental LFDC data measured by A. P.
      Hyvarinen et al. [J. Chem. Phys. 124, 224304 (2006)] were reevaluated using
      transport models at different levels of complexity. Our results indicate that the
      type of fluid dynamical model affects both the position of the nucleation maxima
      in the LFDC and the maximum value of the nucleation rate. On the other hand, the
      Dufour effects and thermodiffusion perceptibly influence only the value of the
      maximal nucleation rate. Its position changes only marginally. The dependence of
      the maximum experimental nucleation rate on the saturation ratio and nucleation
      temperature was acquired for each case. Based on this dependence, we presented a
      method for the comparison and evaluation of the uncertainties of simpler models'
      solutions for the results, where we assumed that the model with Navier-Stokes
      equations and both coupled effects taken into account was the basis. From this
      comparison, it follows that an inappropriate choice of mathematical models could
      lead to relative errors of the order of several hundred percent in the maximum
      experimental nucleation rate. In the conclusion of this study, we also provide
      some general recommendations concerning the proper choice and setting of the
      mathematical model of transport processes in the LFDC.

PMID- 23947875
TI  - Solvent cavitation under solvophobic confinement.
AB  - The stability of liquids under solvophobic confinement can tip in favor of the
      vapor phase, nucleating a liquid-to-vapor phase transition that induces
      attractive forces between confining surfaces. In the case of water adjacent to
      hydrophobic surfaces, experimental and theoretical evidence support confinement
      mediated evaporation stabilization of biomolecular and colloidal assemblies. The
      macroscopic thermodynamic theory of cavitation under confinement establishes the
      connection between the size of the confining surfaces, interfacial free energies,
      and bulk solvent pressure with the critical evaporation separation and
      interfacial forces. While molecular simulations have confirmed the broad
      theoretical trends, a quantitative comparison based on independent measurements
      of the interfacial free energies and liquid-vapor coexistence properties has, to
      the best of our knowledge, not yet been performed. To overcome the challenges of
      simulating a large number of systems to validate scaling predictions for a three
      dimensional fluid, we simulate both the forces and liquid-vapor coexistence
      properties of a two-dimensional Lennard-Jones fluid confined between solvophobic
      plates over a range of plate sizes and reservoir pressures. Our simulations
      quantitatively agree with theoretical predictions for solvent-mediated forces and
      critical evaporation separations once the length dependence of the solvation free
      energy of an individual confining plate is taken into account. The effective
      solid-liquid line tension length dependence results from molecular scale
      correlations for solvating microscopic plates and asymptotically decays to the
      macroscopic value for plates longer than 150 solvent diameters. The success of
      the macroscopic thermodynamic theory at describing two-dimensional liquids
      suggests application to surfactant monolayers to experimentally confirm
      confinement-mediated cavitation. 

PMID- 23947876
TI  - Superhydrophilic graphite surfaces and water-dispersible graphite colloids by
      electrochemical exfoliation.
AB  - Superhydrophilic graphite surfaces and water-dispersible graphite colloids are
      obtained by electrochemical exfoliation with hydrophobic graphite electrodes.
      Such counterintuitive characteristics are caused by partial oxidation and
      investigated by examining both graphite electrodes and exfoliated particles after
      electrolysis. The extent of surface oxidation can be explored through contact
      angle measurement, scanning electron microscope, electrical sheet resistance, x
      ray photoelectron spectroscopy, zeta-potential analyzer, thermogravimetric
      analysis, UV-visible, and Raman spectroscopy. The degree of wettability of the
      graphite anode can be altered by the electrolytic current and time. The water
      contact angle declines generally with increasing the electrolytic current or
      time. After a sufficient time, the graphite anode becomes superhydrophilic and
      its hydrophobicity can be recovered by peeling with adhesive tape. This
      consequence reveals that the anodic graphite is oxidized by oxygen bubbles but
      the oxidation just occurs at the outer layers of the graphite sheet. Moreover,
      the characteristics of oxidation revealed by UV peak shift, peak ratio between D
      and G bands, and negative zeta-potential indicate the presence of graphite oxide
      on the outer shell of the exfoliated colloids. However, thermogravimetric
      analysis for the extent of decomposition of oxygen functional groups verifies
      that the amount of oxygen groups is significantly less than that of graphite
      oxide prepared via Hummer method. The structure of this partially oxidized
      graphite may consist of a graphite core covered with an oxidized shell. The
      properties of the exfoliated colloids are also influenced by pH of the
      electrolytic solution. As pH is increased, the extent of oxidation descends and
      the thickness of oxidized shell decreases. Those results reveal that the degree
      of oxidation of exfoliated nanoparticles can be manipulated simply by controlling
      pH. 

PMID- 23947877
TI  - The nature of free O-H stretching in water adsorbed on carbon nanosystems.
AB  - Motivated by the existence of several recent works claiming for unusual hydrogen
      bonds in water adsorbed or confined in carbon nanostructures, we have analyzed
      the nature of a sharp O-H stretching at 3700 cm(-1) in H2O/graphene recorded in
      vibrational measurements. The interpretation of such mode is rather
      controversial. On the basis of a careful inspection of our spectroscopic data and
      of literature, we suggest that the interpretation of this feature as a
      fingerprint of surface hydrophobicity, electronic effects or disorder is astray.
      Instead, it merely arises from interface effects.

PMID- 23947878
TI  - Water permeation through single-layer graphyne membrane.
AB  - We report the molecular dynamics simulations of spontaneous and continuous
      permeation of water molecules through a single-layer graphyne-3 membrane. We
      found that the graphyne-3 membrane is more permeable to water molecules than (5,
      5) carbon nanotube membranes of similar pore diameter. The remarkable hydraulic
      permeability of the single-layer graphyne-3 membrane is attributed to the
      hydrogen bond formation, which connects the water molecules on both sides of the
      monolayer graphyne-3 membrane and aids to overcome the resistance of the
      nanopores, and to the relatively lower energy barrier at the pore entrance.
      Consequently, the single-layer graphyne-3 membrane has a great potential for
      application as membranes for desalination of sea water, filtration of polluted
      water, etc. 

PMID- 23947879
TI  - Precision control of charge coherence in parallel double dot systems through spin
      orbit interaction.
AB  - In terms of the exact quantum master equation solution for open electronic
      systems, the coherent dynamics of two charge states described by two parallel
      quantum dots with one fully polarized electron on either dot is investigated in
      the presence of spin-orbit interaction. We demonstrate that the double dot system
      can stay in a dynamically decoherence free space. The coherence between two
      double dot charge states can be precisely manipulated through a spin-orbit
      coupling. The effects of the temperature, the finite bandwidth of lead, and the
      energy deviations during the coherence manipulation are also explored. 

PMID- 23947880
TI  - Computational design of chemically propelled catalytic nanorotors.
AB  - We designed catalytic nanorotors and investigated the rotational motion and
      energy conversion efficiency using reactive molecular dynamics in two dimensions.
      First, a two-arm nanorotor was constructed by decorating a slender beam with
      catalysts asymmetrically on its two long edges, while fixing the beam center as
      the rotational axis. Autonomous rotation was observed for the two-arm nanorotor
      immersing in a fuel environment. Here fuel molecules undergo exothermic
      combination reaction facilitated by the catalysts. It was found that the angular
      velocity increases with the catalyst coverage parabolically, while the rotary
      nanomotor efficiency stays roughly constant. These observations are consistent
      with a single-collision-momentum-transfer-based propulsion model. Furthermore,
      multi-arm nanorotors (up to eight arms) were constructed by carving radially
      distributed arms followed by decorating catalysts. For multi-arm nanorotors, both
      the angular velocity and the efficiency decrease as the number of arms increases.
      These behaviors contradict the aforementioned model, which are likely due to the
      deceleration from secondary collisions between products and the nanorotor arms.
      Our simulation results show that the optimal design for a nanorotor that
      maximizes its angular velocity and the motor efficiency is a two-arm nanorotor
      with nearly full coverage of catalysts. 

PMID- 23947881
TI  - Interfacial behavior of simple inorganic salts at the air-water interface
      investigated with a polarizable model with electrostatic damping.
AB  - New molecular models that incorporated polarizable interactions with
      electrostatic damping were developed to better understand the interfacial
      properties of aqueous electrolyte systems. The models were parameterized to give
      free energies of aqueous solvation and the change in activity with respect to
      concentration in agreement with experiment. Specifically, we investigated NaCl,
      NaBr, and NaI systems, finding anion propensity for the air-water interface was
      reduced in comparison with previously developed polarizable models. This
      coincided with a more negative surface excess than that given by previously
      developed polarizable models. Furthermore, we investigated the interfacial
      properties of SrCl2 aqueous systems, finding that strontium had a moderate
      enhancement in interfacial density in comparison with bulk, while still having a
      fairly large negative surface excess, in agreement with experimental results. 

PMID- 23947882
TI  - An exact method to obtain effective electrostatic interactions from computer
      simulations: the case of effective charge amplification.
AB  - We discuss here an exact method to determine the parameters regulating the
      screened Coulomb interactions among spherical macroions immersed in a simple
      electrolyte. This approach provides rigorous definitions for the corresponding
      screening length, effective permittivity, and renormalized charges, and can be
      employed for precise and reliable calculations of these parameters within any
      scheme. In particular, we introduce a simple procedure for extracting this
      information from computer simulations. The viability of this approach is
      demonstrated by applying it to a three-component model system which includes
      anionic nanoparticles and monovalent cations and anions. The mean forces between
      nanoparticles are determined directly from simulations with two macroions, plus
      small ions, inside a single cell with periodic boundary conditions. The values of
      the parameters of interest, on the other hand, are gathered from two separate
      sets of computer simulations: one set provides information about the short-range
      correlations among the small ions, which in turn determine the screening length
      and effective permittivity; the second set supplies the short-range components of
      the ionic distribution around one isolated macroion, which also determine its
      renormalized charge. The method presented here thus avoids the uncertain fitting
      of these parameters from the asymptotic tail of the mean force and allows us to
      investigate in detail this connection between the renormalized charge of the
      macroion and the short-range (virtual) part of the ionic cloud surrounding it.
      Using the standard prescription to extract an effective charge from the
      corresponding renormalized value, we then proceed to clarify the mechanisms
      behind the possibility of effective charge amplification (i.e., an effective
      charge larger than the bare macroion charge). Complementarily, we report results
      for the corresponding bridge functions too. 

PMID- 23947883
TI  - Translational and rotational diffusion of gold nanorods near a wall.
AB  - We measured the rotational and translational diffusivity of dilute gold nanorods
      in aqueous suspension close to a hard planar wall. Therefore, resonance enhanced
      dynamic light scattering, an evanescent technique, was applied, making use of the
      strong scattering intensity near the longitudinal surface plasmon resonance
      frequency of the particle. We observed a slowing down beyond the known
      hydrodynamic models. 

PMID- 23947884
TI  - Understanding the relationship between molecular order and charge transport
      properties in conjugated polymer based organic blend photovoltaic devices.
AB  - We report a detailed characterization of the thin film morphology of all-polymer
      blend devices by applying a combined analysis of physical, chemical, optical, and
      charge transport properties. This is exemplified by considering a model system
      comprising poly(3-hexylthiophene) (P3HT) and poly(9,9-dioctylfluorene-co
      benzothiadiazole) (F8BT). We show that the interactions between the two
      conjugated polymer components can be controlled by pre-forming the P3HT into
      highly ordered nanowire structures prior to blending with F8BT, and by varying
      the molecular weight of the F8BT. As a result, it is possible to produce films
      containing highly ordered P3HT with hole mobilities enhanced by three orders of
      magnitude over the pristine blends. Raman spectroscopy under resonant excitation
      conditions is used to probe the molecular order of both P3HT and F8BT phases
      within the blend films and these morphological studies are complemented by
      measurements of photocurrent generation. The resultant increase in photocurrent
      is associated with the enhanced charge carrier mobilities. The complementary
      analytical method demonstrated here is applicable to a wide range of polymer
      blend systems for all applications where the relationships between morphology and
      device performance are of interest. 

PMID- 23947885
TI  - Compressive force generation by a bundle of living biofilaments.
AB  - To study the compressional forces exerted by a bundle of living stiff filaments
      pressing on a surface, akin to the case of an actin bundle in filopodia
      structures, we have performed particulate molecular dynamics simulations of a
      grafted bundle of parallel living (self-assembling) filaments, in chemical
      equilibrium with a solution of their constitutive monomers. Equilibrium is
      established as these filaments, grafted at one end to a wall of the simulation
      box, grow at their chemically active free end, and encounter the opposite
      confining wall of the simulation box. Further growth of filaments requires
      bending and thus energy, which automatically limit the populations of longer
      filaments. The resulting filament sizes distribution and the force exerted by the
      bundle on the obstacle are analyzed for different grafting densities and
      different sub- or supercritical conditions, these properties being compared with
      the predictions of the corresponding ideal confined bundle model. In this
      analysis, non-ideal effects due to interactions between filaments and confinement
      effects are singled out. For all state points considered at the same temperature
      and at the same gap width between the two surfaces, the force per filament
      exerted on the opposite wall appears to be a function of a rescaled free monomer
      density rho1(eff). This quantity can be estimated directly from the
      characteristic length of the exponential filament size distribution P observed in
      the size domain where these grafted filaments are not in direct contact with the
      wall. We also analyze the dynamics of the filament contour length fluctuations in
      terms of effective polymerization (U) and depolymerization (W) rates, where again
      it is possible to disentangle non-ideal and confinement effects.

PMID- 23947886
TI  - Are structural properties of dendrimers sensitive to the symmetry of branching?
      Computer simulation of lysine dendrimers.
AB  - Poly-L-lysine (PLL) dendrimers are promising systems for biomedical applications
      due to their biocompatibility. These dendrimers have a specific topology: two
      spacers of different lengths come out of each branching point and thus the
      branching is asymmetric. Because of this asymmetry terminal groups are located at
      branches of different lengths, unlike dendrimers with a symmetric branching. This
      paper presents the results of the first systematic molecular dynamics simulation
      of such asymmetric PLL dendrimers. It is shown that PLL dendrimers are porous
      molecules with all terminal groups equally accessible to water. We have found
      that in spite of an asymmetry of branching the general structural characteristics
      of PLL dendrimers are rather similar to those of dendrimers with symmetric
      branching. We have also found that the structural characteristics of PLL
      dendrimers obey the general laws for dendrimers and that their electrostatic
      properties agree with the predictions of a general analytic theory. 

PMID- 23947887
TI  - Influence of the surface charge on the homogeneity of colloidal crystals.
AB  - Five groups of suspensions composed of polystyrene particles, having similar size
      but different effective surface charge, were adopted to investigate the effects
      of surface charge and volume fraction on the homogeneity of colloidal crystals
      through checking the difference between D(exp) and D(uni) by reflection
      spectroscopy method (D(exp), D(uni) are the experimental and the expected value
      of the average nearest neighbor interparticle distance by assuming a uniform
      structure, respectively). We found volume fractions (ranging from 0.006 to 0.02)
      and structure types basically have no influence on the values of D(exp)/D(uni).
      Moreover, for crystals formed by lowly charged particles, D(exp)/D(uni) is
      approximately equal to 1, implying the crystals are homogeneous. With the
      increase of effective surface charge, D(exp) gradually deviates from D(uni) and
      the formed crystals become inhomogeneous. Our experimental observations are in
      accordance with the previous simulation results. Additionally, we also found
      D(exp)/D(uni) initially drops quickly with increasing effective surface charge
      and then it tends to an asymptotic value (~0.85), it is supposedly due to the
      saturation of effective charge. Our relevant computer simulations confirmed that
      the study scheme that using D(exp)/D(uni) as an indicator to assess the
      homogeneity of crystal structure is tenable and the simulation results are
      consistent with experiments.

PMID- 23947888
TI  - Dissipative particle dynamics simulations on self-assembly of rod-coil-rod
      triblock copolymers in a rod-selective solvent.
AB  - Self-assembly of rod-coil-rod ABA triblock copolymers in a rod-selective solvent
      is investigated by using dissipative particle dynamics simulations. The
      morphologies of the self-assembled aggregates are dependent on the number of
      copolymers in the aggregate and the rod length of the copolymer. We observe
      vesicles at short rod block and bowl-like aggregates at slightly longer rod
      block. In the vesicle region near the phase boundary, metastable bowl-like
      aggregates can be observed and be transformed into vesicles by annealing process.
      A transition from the bowl-like structure to the vesicle is observed by
      increasing the solvophobicity of the mid-coil block. In this study, the
      difference between the self-assembly of fully flexible ABA triblock copolymer and
      that of rod-coil-rod triblock copolymer is also discussed. 

PMID- 23947889
TI  - Effective charge of ionic microgel particles in the swollen and collapsed states:
      the role of the steric microgel-ion repulsion.
AB  - In this work the system formed by charged (ionic) microgels in the presence of
      monovalent salt is investigated by solving numerically the Ornstein-Zernike
      integral equations within the Hypernetted-Chain approximation. The ionic density
      profiles, effective interaction between microgel particles, and the effective
      charge of the particles are calculated. In addition to the electrostatic
      interaction, the excluded-volume repulsion between the microgel particle and the
      ions is also explicitly taken into account. Although this steric interaction is
      irrelevant in the swollen state (when the packing fraction of the polymer network
      is low), it becomes a very important contribution close to the de-swollen state,
      hindering the counterion penetration inside the microgel mesh. The theoretical
      predictions indicate that the ionic density profiles are strongly affected by the
      degree of swelling, going from a volumetric distribution of counterions in the
      swollen state to a surface accumulation outside the particle that becomes more
      important as the particle shrinks. The electrostatic effective interaction
      between pairs of microgel particles is shown to be the result of a complex
      interplay between electrostatic and depletion effects that strongly depend on the
      bare charge density of the particle. For sufficiently charged microgel particles,
      the steric exclusion leads to a less efficient screening of the microgel charge
      near the de-swollen configuration, and so to a significant increase of the
      effective charge of the microgel particle. 

PMID- 23947890
TI  - Spatially dependent relative diffusion of nanoparticles in polymer melts.
AB  - We formulate and apply a microscopic statistical-mechanical theory for the non
      hydrodynamic relative diffusion coefficient of a pair of spherical nanoparticles
      in entangled polymer melts based on a combination of Brownian motion, mode
      coupling, and polymer physics ideas. The focus is on the mesoscopic regime where
      particles are larger than the entanglement spacing. The dependence of the non
      hydrodynamic friction on interparticle separation, degree of entanglement, and
      tube diameter is systematically studied. The overall magnitude of the relative
      diffusivity is controlled by the ratio of the particle to tube diameter and the
      number of entanglements in a manner reminiscent of single-particle self-diffusion
      and Stokes-Einstein violations. A rich spatial separation dependence of mobility
      enhancement relative to the hydrodynamic behavior is predicted even for very
      large particles, and the asymptotic dependence is derived analytically in the
      small and large separation limits. Particle separations in excess of 100 nm are
      sometimes required to recover the hydrodynamic limit. The effects of local
      polymer-particle packing correlations are found to be weak, and the non
      hydrodynamic effects are also small for unentangled melts. 

PMID- 23947892
TI  - Anomalous diffusion of water molecules in hydrated lipid bilayers.
AB  - We present a molecular dynamics (MD) study of the water molecules in a hydrated
      lipid bilayer. Due to the interactions at the surface of a solvated lipid
      membrane, the dynamics of the water and lipid molecules are to some degree
      correlated. In spite of previous efforts reported in the literature, little is
      known about the time and length scales of these correlations. Here, by employing
      a 0.1 MUs long equilibrium MD simulation of a dimyristoylphosphatidylcholine
      (DMPC) lipid bilayer, we show that the waters in a hydrated lipid bilayer can be
      classified into four dynamically connected water layers, and provide a detailed
      analysis of the water dynamics within these four regions. We also show that there
      exists a cooperative molecular motion between the hydration waters and the DMPC
      lipid molecules, and determine the corresponding characteristic time and length
      scales. 

PMID- 23947891
TI  - Anthrax toxin-induced rupture of artificial lipid bilayer membranes.
AB  - We demonstrate experimentally that anthrax toxin complexes rupture artificial
      lipid bilayer membranes when isolated from the blood of infected animals. When
      the solution pH is temporally acidified to mimic that process in endosomes,
      recombinant anthrax toxin forms an irreversibly bound complex, which also
      destabilizes membranes. The results suggest an alternative mechanism for the
      translocation of anthrax toxin into the cytoplasm. 

PMID- 23947893
TI  - A structure-based model fails to probe the mechanical unfolding pathways of the
      titin I27 domain.
AB  - We discuss the use of a structure based Calpha-Go model and Langevin dynamics to
      study in detail the mechanical properties and unfolding pathway of the titin I27
      domain. We show that a simple Go-model does detect correctly the origin of the
      mechanical stability of this domain. The unfolding free energy landscape
      parameters x(u) and DeltaG(?), extracted from dependencies of unfolding forces on
      pulling speeds, are found to agree reasonably well with experiments. We predict
      that above v = 10(4) nm/s the additional force-induced intermediate state is
      populated at an end-to-end extension of about 75 A. The force-induced switch in
      the unfolding pathway occurs at the critical pulling speed v(crit) ~ 10(6)-10(7)
      nm/s. We argue that this critical pulling speed is an upper limit of the interval
      where Bell's theory works. However, our results suggest that the Go-model fails
      to reproduce the experimentally observed mechanical unfolding pathway properly,
      yielding an incomplete picture of the free energy landscape. Surprisingly, the
      experimentally observed intermediate state with the A strand detached is not
      populated in Go-model simulations over a wide range of pulling speeds. The
      discrepancy between simulation and experiment is clearly seen from the early
      stage of the unfolding process which shows the limitation of the Go model in
      reproducing unfolding pathways and deciphering the complete picture of the free
      energy landscape.

PMID- 23947894
TI  - A combination of dynamic light scattering and polarized resonance Raman
      scattering applied in the study of Arenicola Marina extracellular hemoglobin.
AB  - Arenicola Marina extracellular hemoglobin (Hbl Hb) is considered to be a
      promising candidate as a blood substitute. To entangle some of the properties of
      extracellular giant hexagonal bilayer hemoglobin (Hbl Hb) of Arenicola Marina, we
      combined polarized resonance Raman scattering (532 nm excitation) with dynamic
      light scattering (DLS) (632.8 nm). An analysis of the depolarization ratio of
      selected a(2g) skeletal modes of the heme in native Hbl Hb and porcine Hb, shows
      that the distortion of the heme group away from its ideal fourfold symmetry is
      much smaller for heme groups bound in the Hbl Hb than for heme groups bound in
      porcine Hb. Using DLS, the average hydrodynamic diameter (<d(h)>) of Hbl Hb was
      measured at pH = 5, 7, 8, 9, and 10. At pH = 5 to 7, the Hbl Hb was found in its
      native form with <d(h)> equal to 24.2 nm, while at pH = 8 and 9, a dissociation
      process starts to take place resulting in <d(h)> = 9 nm. At pH = 10, only large
      aggregates of fragmented Hbl Hb with <d(h)> larger than 1000 nm was detected,
      however, a comparison of the DLS results with the polarized resonance Raman
      scattering (RRS) revealed that the coupling between the fragments did not involve
      direct interaction between the heme groups, but also that the local heme
      environment seems to be comparable in the aggregates and in the native Hbl Hb. By
      comparing the unpolarized RRS results obtained for erythrocytes (RBC) with those
      for Hbl Hb, led us to the important conclusion that Hbl Hb is much easier
      photolyzed than porcine RBC.

PMID- 23947898
TI  - Association of P2X7 A1513C (rs3751143) gene polymorphism with risk of
      tuberculosis: evidence from a meta-analysis.
AB  - AIM: Many case-control studies have been performed in the past to elucidate the
      association between the P2X7 receptor 1513 A>C (rs3751143) polymorphism and
      tuberculosis (TB) risk. However, their data interpretation was difficult due to
      scattered and inconsistent results that led to limited power. In this study, a
      quantitative summary assessment has been done through meta-analysis to appraise
      the association between the 1513 A>C polymorphism and TB susceptibility.
      METHODOLOGY: Systematic assessment was performed for the published studies
      related with the association between the P2X7 1513 A>C polymorphism and TB risk
      retrieved from PubMed (Medline), EMBASE search. A meta-analysis was done using a
      statistical program to evaluate the said association. Pooled odds ratios (ORs)
      and 95% confidence intervals (95% CIs) were calculated for allele contrast,
      homozygous, heterozygous, dominant, and recessive genetic models. RESULTS: A
      total of 2710 controls and 2521 TB cases were included in this meta-analysis.
      Meta-analysis results showed that C allele carrier status was significantly
      associated with increased TB risk (C vs. A: p=0.001; OR=1.382, 95% CI=1.248
      1.531). Significant risk of TB was associated with the homozygous mutant CC (CC
      vs. AA: p=0.001; OR=1.676, 95% CI=1.251-2.247) and heterozygous AC (AC vs. AA:
      p=0.001; OR=1.429, 95% CI=1.260-1.621) comparisons. Similarly, dominant (CC vs.
      AA+AC: p=0.008; OR=1.481, 95% CI=1.109-1.978) and recessive (CC+AC vs. AA:
      p=0.001; OR=1.458, 95% CI=1.292-1.645) genetic models also revealed increased
      risk of developing TB. CONCLUSION: We found that the P2X7 1513 A>C gene
      polymorphism is significantly associated with increased susceptibility to TB.
      Also, future well-designed epidemiological studies with stratified case-control
      and biological characterization may be beneficial to validate these findings.

PMID- 23947899
TI  - CyclinD1, a prominent prognostic marker for endometrial diseases.
AB  - PURPOSE: Alteration of CyclinD1 was suggested to relate with development of
      endometrial carcinogenesis before, however CyclinD1 expression is not well
      defined in endometrial hyperplasia lesions. We checked the relationship between
      its expression and clinic-pathological variables of endometrial lesions to
      explore the possibility for CyclinD1 as a potential diagnostic and prognostic
      marker. METHODS: Cyclin D1 immunohistochemical analysis (IHC) was used to
      evaluate 201 fixed, paraffin-embedded endometrial samples which included simple
      hyperplasia (n = 27), atypical complex hyperplasia (ACH) (n = 41), endometrioid
      carcinoma (n = 103), endometrial serous carcinoma (ESC) (n = 21) and clear cell
      carcinoma (CCC) (n = 9). A breast cancer with known CyclinD1 expression was
      selected as a positive control in each immunohistochemistry run. We also
      performed follow-up study to estimate patients' prognosis. RESULTS: CyclinD1 was
      significantly overexpressed in atypical complex hyperplasia (ACH), endometrioid
      carcinoma and clear cell carcinoma (CCC). The positive signaling of CyclinD1 was
      showed less than 40% in simple hyperplasia and endometrial serous carcinoma
      (ESC). The high expression of CyclinD1 was observed in metastasis carcinoma group
      more significantly than non-metastasis carcinoma group. Kaplan Meier analysis
      demonstrated that patients with high CyclinD1 expression had an obviously poor
      prognosis than patients without CyclinD1 staining (p < 0.05). Moreover, according
      to multivariate Cox regression analysis, CyclinD1 expression, as crucial as
      metastasis, was a risk marker for overall survival rate. CONCLUSION: CyclinD1
      exhibited a promising potential to predict the prognosis of patients with
      endometrial carcinoma. However, the statistical analysis demonstrated that
      CyclinD1 exhibited a poor ability to differentiate neoplastic lesions from non
      neoplastic lesions; thus, the application of CyclinD1 only is not so credible for
      differentiation between benign and malignant lesions. VIRTUAL SLIDES: The virtual
      slides for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1871063048950173.

PMID- 23947900
TI  - The development and evaluation of the DK-20: a knowledge of dementia measure.
AB  - BACKGROUND: Raising understanding of dementia has become a key focus of
      international health and social care. An up-to-date, psychometrically sound
      measure of dementia knowledge that embraces a biopsychosocial perspective is
      lacking. The aim of this study is to develop and evaluate the psychometric
      properties of the DK-20, a dementia knowledge questionnaire aimed at unqualified
      care staff. METHODS: Domain and item generation followed recommended measure
      development procedures. A pilot and large-scale study evaluated the psychometric
      properties of the measure on a sample of 211 care staff and other dementia
      professionals. RESULTS: The final 20-item measure encompasses items based on
      biopsychosocial dementia knowledge and care-specific knowledge. Acceptable test
      retest reliability, marginal levels of internal consistency, and evidence for
      face, content, and construct validity were demonstrated. CONCLUSIONS: The DK-20
      is the first knowledge of dementia measure to be developed specifically for
      unqualified care staff and has reasonable psychometric properties. It may be used
      to identify gaps in knowledge, highlighting areas for inclusion in educational
      interventions.

PMID- 23947902
TI  - The CASCADE trial: effectiveness of ceramic versus PEEK cages for anterior
      cervical discectomy with interbody fusion; protocol of a blinded randomized
      controlled trial.
AB  - BACKGROUND: Anterior cervical discectomy with interbody fusion cages is
      considered the standard surgical procedure in patients with cervical disc
      herniation. However, PEEK or metal cages have some undesirable imaging
      characteristics, leading to a search for alternative materials not creating
      artifacts on images; silicon nitride ceramic. Whether patients treated with
      silicon nitride ceramic cages have similar functional outcome as patients treated
      with PEEK cages is not known. We present the design of the CASCADE trial on
      effectiveness of ceramic cages versus PEEK cages in patients with cervical disc
      herniation and/or osteophytes. METHODS/DESIGN: Patients (age 18-75 years) with
      monoradicular symptoms in one or both arms lasting more than 8 weeks, due to disc
      herniation and/or osteophytes, are eligible for the trial. The study is designed
      as a randomized controlled equivalence trial in which patients are blinded to the
      type of cage for 1 year. The total follow-up period is 2 years. The primary
      outcome measure is improvement in the Neck and Disability Index (NDI). Secondary
      outcomes measures include improvement in arm pain and neck pain (VAS), SF-36 and
      patients' perceived recovery. The final elements of comparison are perioperative
      statistics including operating time, blood loss, length of hospital stay, and
      adverse events. Lateral plane films at each follow-up visit and CT scan (at 6
      months) will be used to judge fusion and the incidence of subsidence. Based on a
      power of 90% and assuming 8% loss to follow-up, 100 patients will be randomized
      into the 2 groups. The first analysis will be conducted when all patients have 1
      year of follow-up, and the groups will be followed for 1 additional year to judge
      stability of outcomes. DISCUSSION: While the new ceramic cage has received the CE
      Mark based on standard compliance and animal studies, a randomized comparative
      study with the golden standard product will provide more conclusive information
      for clinicians. Implementation of any new device should only be done after
      completion of randomized controlled effectiveness trials.

PMID- 23947903
TI  - Profiles and experiences of women undergoing genital fistula repair: findings
      from five countries.
AB  - This article presents data from 1354 women from five countries who participated
      in a prospective cohort study conducted between 2007 and 2010. Women undergoing
      surgery for fistula repair were interviewed at the time of admission, discharge,
      and at a 3-month follow-up visit. While women's experiences differed across
      countries, a similar picture emerges across countries: women married young, most
      were married at the time of admission, had little education, and for many, the
      fistula occurred after the first pregnancy. Median age at the time of fistula
      occurrence was 20.0 years (interquartile range 17.3-26.8). Half of the women
      attended some antenatal care (ANC); among those who attended ANC, less than 50%
      recalled being told about signs of pregnancy complications. At follow-up, most
      women (even those who were not dry) reported improvements in many aspects of
      social life, however, reported improvements varied by repair outcome. Prevention
      and treatment programmes need to recognise the supportive role that husbands,
      partners, and families play as women prepare for safe delivery. Effective
      treatment and support programmes are needed for women who remain incontinent
      after surgery. 

PMID- 23947904
TI  - Isolation and sequence determination of tetrapeptide from Selaginella bryopteris.
AB  - A simple and inexpensive paper chromatographic method was developed for the
      isolation of a small peptide from Selaginella bryopteris fronds. The content of
      peptides is low in most plants and the isolation and purification procedure is
      troublesome. This method may be used as a first step for the detection of small
      peptides in the plant extracts. De novo sequence determination by tandem mass
      spectrometry indicated that the peptide is a tetrapeptide. 

PMID- 23947905
TI  - Fixed subaortic stenosis: a clinical dilemma for clinicians and patients.
AB  - Subaortic stenosis carries considerable morbidity and mortality. In most cases,
      patients have an underlying left ventricular outflow tract morphology that
      promotes turbulence at the outflow tract, which induces the development of
      subaortic fibromuscular tissue. A subset of patients will progress to develop
      severe stenosis and aortic regurgitation, but it has been difficult to determine
      which patients are at risk. While resection of the subaortic tissue improves
      immediate outcome, many patients have recurrence of both stenosis and
      regurgitation, questioning the efficacy of surgical intervention in asymptomatic
      patients. This review article describes the current understanding of the
      etiology, treatment, and prognosis of subaortic stenosis. 

PMID- 23947906
TI  - Tribute to Joel M. Bowman.

PMID- 23947907
TI  - Autobiography of Joel M. Bowman.

PMID- 23947910
TI  - Experimental and theoretical study of multi-quantum vibrational excitation: NO(v
      = 0->1,2,3) in collisions with Au(111).
AB  - We measured absolute probabilities for vibrational excitation of NO(v = 0)
      molecules in collisions with a Au(111) surface at an incidence energy of
      translation of 0.4 eV and surface temperatures between 300 and 1100 K. In
      addition to previously reported excitation to v = 1 and v = 2, we observed
      excitation to v = 3. The excitation probabilities exhibit an Arrhenius dependence
      on surface temperature, indicating that the dominant excitation mechanism is
      nonadiabatic coupling to electron-hole pairs. The experimental data are analyzed
      in terms of a recently introduced kinetic model, which was extended to include
      four vibrational states. We describe a subpopulation decomposition of the kinetic
      model, which allows us to examine vibrational population transfer pathways. The
      analysis indicates that sequential pathways (v = 0 -> 1 -> 2 and v = 0 -> 1 -> 2 
      > 3) alone cannot adequately describe production of v = 2 or 3. In addition, we
      performed first-principles molecular dynamics calculations that incorporate
      electronically nonadiabatic dynamics via an independent electron surface hopping
      (IESH) algorithm, which requires as input an ab initio potential energy
      hypersurface (PES) and nonadiabatic coupling matrix elements, both obtained from
      density functional theory (DFT). While the IESH-based simulations reproduce the v
      = 1 data well, they slightly underestimate the excitation probabilities for v =
      2, and they significantly underestimate those for v = 3. Furthermore, this
      implementation of IESH appears to overestimate the importance of sequential
      energy transfer pathways. We make several suggestions concerning ways to improve
      this IESH-based model. 

PMID- 23947911
TI  - Isolated complete caudate lobectomy for hepatic tumor of the anterior
      transhepatic approach: surgical approaches and perioperative outcomes.
AB  - BACKGROUND: How to resect the caudate lobe safely is a major challenge to current
      liver surgery which requires further study. METHODS: Nine cases (6 hepatic cell
      carcinoma, 2 cavernous hemangioma and 1 intrahepatic cholangiocacinoma) were
      performed using the anterior transhepatic approach in the isolated complete
      caudate lobe resection. During the operation, we used the following techniques:
      the intraoperative routine use of Peng's multifunction operative dissector
      (PMOD), inflow and outflow of hepatic blood control, low central venous pressure
      and selective use of liver hanging maneuver. RESULTS: There were no perioperative
      deaths observed after the operation. The median operating time was 230 +/- 43.6
      minutes, the median intraoperative blood loss was 606.6 +/- 266.3 ml and the
      median length of postoperative hospital stay was 12.6 +/- 2.9 days. The incidence
      of complications was 22.22% (2/9). CONCLUSION: PMOD and "curettage and
      aspiration" technique can be of great help of in the dissection of vessels and
      parenchyma, clearly making caudate lobe resection safer, easier and faster.

PMID- 23947912
TI  - High-resolution MS, MS/MS, and UV database of fungal secondary metabolites as a
      dereplication protocol for bioactive natural products.
AB  - A major problem in the discovery of new biologically active compounds from
      natural products is the reisolation of known compounds. Such reisolations waste
      time and resources, distracting chemists from more promising leads. To address
      this problem, dereplication strategies are needed that enable crude extracts to
      be screened for the presence of known compounds before isolation efforts are
      initiated. In a project to identify anticancer drug leads from filamentous fungi,
      a significant dereplication challenge arises, as the taxonomy of the source
      materials is rarely known, and, thus, the literature cannot be probed to identify
      likely known compounds. An ultraperformance liquid chromatography-photodiode
      array-high-resolution tandem mass spectrometric (UPLC-PDA-HRMS-MS/MS) method was
      developed for dereplication of fungal secondary metabolites in crude culture
      extracts. A database was constructed by recording HRMS and MS/MS spectra of
      fungal metabolites, utilizing both positive- and negative-ionization modes.
      Additional details, such as UV-absorption maxima and retention times, were also
      recorded. Small-scale cultures that showed cytotoxic activities were dereplicated
      before engaging in the scale-up or purification processes. Using these methods,
      approximately 50% of the cytotoxic extracts could be eliminated from further
      study after the confident identification of known compounds. The specific
      attributes of this dereplication methodology include a focus on bioactive
      secondary metabolites from fungi, the use of a 10 min chromatographic method, and
      the inclusion of both HRMS and MS/MS data. 

PMID- 23947913
TI  - pH-sensitive micelles for targeted drug delivery prepared using a novel membrane
      contactor method.
AB  - A novel membrane contactor method was used to produce size-controlled
      poly(ethylene glycol)-b-polycaprolactone (PEG-PCL) copolymer micelles composed of
      diblock copolymers with different average molecular weights, Mn (9200 or 10,400
      Da) and hydrophilic fractions, f (0.67 or 0.59). By injecting 570 L m(-2) h(-1)
      of the organic phase (a 1 mg mL(-1) solution of PEG-PCL in tetrahydrofuran)
      through a microengineered nickel membrane with a hexagonal pore array and 200 MUm
      pore spacing into deionized water agitated at 700 rpm, the micelle size linearly
      increased from 92 nm for a 5-MUm pore size to 165 nm for a 40-MUm pore size. The
      micelle size was finely tuned by the agitation rate, transmembrane flux and
      aqueous to organic phase ratio. An encapsulation efficiency of 89% and a drug
      loading of ~75% (w/w) were achieved when a hydrophobic drug (vitamin E) was
      entrapped within the micelles, as determined by ultracentrifugation method. The
      drug-loaded micelles had a mean size of 146 +/- 7 nm, a polydispersity index of
      0.09 +/- 0.01, and a zeta potential of -19.5 +/- 0.2 mV. When drug-loaded
      micelles where stored for 50 h, a pH sensitive drug release was achieved and a
      maximum amount of vitamin E (23%) was released at the pH of 1.9. When a pH
      sensitive hydrazone bond was incorporated between PEG and PCL blocks, no
      significant change in micelle size was observed at the same micellization
      conditions.

PMID- 23947914
TI  - The development of chronic cough in children following presentation to a tertiary
      paediatric emergency department with acute respiratory illness: study protocol
      for a prospective cohort study.
AB  - BACKGROUND: Acute respiratory illness, a leading cause of cough in children,
      accounts for a substantial proportion of childhood morbidity and mortality
      worldwide. In some children acute cough progresses to chronic cough (>4 weeks
      duration), impacting on morbidity and decreasing quality of life. Despite the
      importance of chronic cough as a cause of substantial childhood morbidity and
      associated economic, family and social costs, data on the prevalence, predictors,
      aetiology and natural history of the symptom are scarce. This study aims to
      comprehensively describe the epidemiology, aetiology and outcomes of cough during
      and after acute respiratory illness in children presenting to a tertiary
      paediatric emergency department. METHODS/DESIGN: A prospective cohort study of
      children aged <15 years attending the Royal Children's Hospital Emergency
      Department, Brisbane, for a respiratory illness that includes parent reported
      cough (wet or dry) as a symptom. The primary objective is to determine the
      prevalence and predictors of chronic cough (>=4 weeks duration) post presentation
      with acute respiratory illness. Demographic, epidemiological, risk factor,
      microbiological and clinical data are completed at enrolment. Subjects complete
      daily cough dairies and weekly follow-up contacts for 28(+/-3) days to ascertain
      cough persistence. Children who continue to cough for 28 days post enrolment are
      referred to a paediatric respiratory physician for review. Primary analysis will
      be the proportion of children with persistent cough at day 28(+/-3). Multivariate
      analyses will be performed to evaluate variables independently associated with
      chronic cough at day 28(+/-3). DISCUSSION: Our protocol will be the first to
      comprehensively describe the natural history, epidemiology, aetiology and
      outcomes of cough during and after acute respiratory illness in children. The
      results will contribute to studies leading to the development of evidence-based
      clinical guidelines to improve the early detection and management of chronic
      cough in children during and after acute respiratory illness.

PMID- 23947915
TI  - Effect of adjunctive roxithromycin therapy on interleukin-1beta, transforming
      growth factor-beta1 and vascular endothelial growth factor in gingival crevicular
      fluid of cyclosporine A-treated patients with gingival overgrowth.
AB  - BACKGROUND AND OBJECTIVE: Systemic macrolide antibiotic administration has been
      shown to result in the elimination or reduction cyclosporine A-induced gingival
      overgrowth. Roxithromycin (ROX) is known to have anti-inflammatory,
      immunomodulatory and tissue reparative effects. This study was to evaluate the
      effect of adjunctive ROX therapy on cyclosporine A-induced gingival overgrowth
      and interleukin (IL)-1beta, transforming growth factor (TGF)-beta1 and vascular
      endothelial growth factor (VEGF) levels in gingival crevicular fluid of renal
      transplant patients. MATERIAL AND METHODS: Thirty-one patients with clinically
      significant overgrowth and 16 periodontally healthy subjects were included in
      this randomized, double-blind, placebo-controlled, parallel-arm study. Patients
      received scaling and root planing (SRP) at baseline and randomized to take either
      ROX or placebo for 5 d. The clinical parameters, including plaque index,
      papillary bleeding index, probing depth and gingival overgrowth scores, were
      recorded. The amounts of IL-1beta, TGF-beta1 and VEGF in gingival crevicular
      fluid were detected by ELISA. Periodontal parameters as well as gingival
      crevicular fluid biomarker levels were evaluated at baseline and at 1 and 4 wk
      post-therapy. RESULTS: Following SRP plus ROX and SRP plus placebo therapy,
      significant improvements in clinical periodontal parameters of both study groups
      were observed (p < 0.025). In the ROX group, adjunctive ROX therapy resulted in a
      greater gingival overgrowth scores reduction compared with those in the placebo
      group at 4 wk (p < 0.017). Initial amounts of IL-1beta, TGF-beta1 and VEGF for
      both the ROX and placebo groups were significantly higher than those for healthy
      subjects (p < 0.017), with no statistical difference between the two study
      groups. At 1 and 4 wk post-therapy, significant decreases in the amounts of IL
      1beta, TGF-beta1 and VEGF were observed in both study groups when compared with
      baseline (p < 0.025), but there was no difference in the levels of IL-1beta and
      VEGF between the two study groups. The amount of decrease in TGF-beta1 levels for
      the ROX group was statistically significant compared to that for the placebo
      group at 4 wk after treatment (p < 0.017). CONCLUSION: Our study indicated that
      combination of ROX with non-surgical therapy improves gingival overgrowth status
      and decreases gingival crevicular fluid TGF-beta1 levels in patients with severe
      gingival overgrowth. The reduction of gingival crevicular fluid TGF-beta1
      following ROX therapy suggests an anti-inflammatory/immunomodulatory effect of
      ROX on the treatment of cyclosporine A-induced gingival overgrowth.

PMID- 23947917
TI  - Contribution of electrostatics to the binding of pancreatic-type ribonucleases to
      membranes.
AB  - Pancreatic-type ribonucleases show clinical promise as chemotherapeutic agents
      but are limited in efficacy by the inefficiency of their uptake by human cells.
      Cellular uptake can be increased by the addition of positive charges to the
      surface of ribonucleases, either by site-directed mutagenesis or by chemical
      modification. This observation has led to the hypothesis that ribonuclease uptake
      by cells depends on electrostatics. Here, we use a combination of experimental
      and computational methods to ascertain the contribution of electrostatics to the
      cellular uptake of ribonucleases. We focus on three homologous ribonucleases:
      Onconase (frog), ribonuclease A (cow), and ribonuclease 1 (human). Our results
      support the hypothesis that electrostatics are necessary for the cellular uptake
      of Onconase. In contrast, specific interactions with cell-surface components
      likely contribute more to the cellular uptake of ribonuclease A and ribonuclease
      1 than do electrostatics. These findings provide insight for the design of new
      cytotoxic ribonucleases. 

PMID- 23947918
TI  - Evaluation of ATR-FTIR spectroscopy with multivariate analysis to study the
      binding mechanisms of ZnO nanoparticles or Zn2+ to Chelex-100 or metsorb.
AB  - Advancements in nanotechnology and the expected increases in production of
      commercial products with incorporated manufactured nanomaterials will very likely
      lead to increasing contamination of nanoparticles (NPs) in the environment.
      Though studying adverse impacts of NPs in the environment and their
      ecotoxicological fate and behavior is not new, limited information is available.
      A major challenge in this respect is the lack of a proper sampling technique that
      could provide data on concentrations of these materials in the environment.
      Diffusive gradient in thin-films (DGT) is a well-established method that can
      measure available concentrations of trace metals in soils and waters. Using this
      approach, different binding resins are employed as a sink to collect targeted
      chemicals during fixed times. Here, we examine the suitability of two common
      types of the DGT binding agents, commercially available Chelex-100 and Metsorb,
      to investigate whether these materials could irreversibly retain a model
      nanoparticle, ZnO, and if so, what would be the difference between bound ZnO NP
      and Zn(2+) ion. Attenuated total reflection-Fourier transform infrared (ATR-FTIR)
      spectroscopy was used to study the binding materials before and after exposure to
      ZnO NP and Zn(2+). Based on computational analysis using principal component
      analysis and linear discriminant analysis (PCA-LDA), it was demonstrated that
      both Chelex-100 and Metsorb form chemical bonds with ZnO NP and Zn(2+), however
      the binding mechanisms of these zinc species as inferred from their infrared (IR)
      spectra are statistically different (95% confidence level). The experimental
      results suggest that the binding resins hold ZnO NP with fewer and weaker
      chemical bonds compared to Zn(2+). This research shows the potential of the DGT
      method to measure available concentrations of nanoparticles in the environment
      and demonstrate how ATR-FTIR spectroscopy, when used with computational analysis,
      can differentiate between diverse chemical species that are simultaneously
      retained by the binding layer in a DGT device. 

PMID- 23947919
TI  - Eosinophilic esophagitis in children with esophageal atresia.
AB  - Eosinophilic esophagitis (EoE) has only rarely been reported in esophageal
      atresia (EA) patients. A retrospective case analysis of all EA patients born at
      our center between January 1999 and April 2012 was performed. A total of 113 of
      patients were identified; 10 patients were excluded as a result of inadequate
      data. Eighteen patients (17%) were diagnosed with EoE. The average number of
      eosinophilis was 30/high-power field (HPF) (19/HPF-80/HPF). The median age for
      diagnosis of EoE was 1 year and 6 months (8 months-8 years and 7 months).
      Children with EoE had a significantly greater incidence of reflux symptoms,
      dysphagia, tracheomalacia, and 'hypoxic spells' (P < 0.05). EoE patients also
      underwent significantly more surgery including fundoplication and aortopexy when
      compared with those without EoE (P < 0.0001). Although the incidence of
      gastrostomy was greater in the EoE group (33% vs. 13%), this was not
      statistically significant. Half of the EoE patients had a coexisting atopic
      condition at time of diagnosis. The commonest condition was asthma 7/18 (38%)
      followed by specific food allergy 6/18 (33%). EoE was treated in 11 patients with
      either swallowed fluticasone or budesonide slurry. All improved clinically.
      Histologically, five had complete resolution and six had partial improvement. Six
      children with EoE were treated with acid suppression alone. All improved
      clinically, and 5/6 had subsequent histological resolution. One child who
      received acid suppression and an exclusion diet also improved. Seven patients
      (38%) had an esophageal stricture at time of EoE diagnosis. Five were dilated at
      time of the initial endoscopy, prior to the diagnosis of EoE being available. Two
      patients had resolution of their strictures on medical treatment of their EoE
      alone and did not require further dilatation. EoE was seen in 17% of children
      with EA in this study. EoE should be considered in EA patients with persistent
      symptoms on standard reflux treatment, increasing dysphagia, and recurrent
      strictures. 

PMID- 23947921
TI  - Personality disorders in older adults: expert opinion as a first step toward
      evaluating the criterion validity of an informant questionnaire (HAP).

PMID- 23947920
TI  - Effects of ventilation strategy on distribution of lung inflammatory cell
      activity.
AB  - INTRODUCTION: Leukocyte infiltration is central to the development of acute lung
      injury, but it is not known how mechanical ventilation strategy alters the
      distribution or activation of inflammatory cells. We explored how protective (vs.
      injurious) ventilation alters the magnitude and distribution of lung leukocyte
      activation following systemic endotoxin administration. METHODS: Anesthetized
      sheep received intravenous endotoxin (10 ng/kg/min) followed by 2 h of either
      injurious or protective mechanical ventilation (n = 6 per group). We used
      positron emission tomography to obtain images of regional perfusion and shunting
      with infused 13N[nitrogen]-saline and images of neutrophilic inflammation with
      18F-fluorodeoxyglucose (18F-FDG). The Sokoloff model was used to quantify 18F-FDG
      uptake (Ki), as well as its components: the phosphorylation rate (k3, a surrogate
      of hexokinase activity) and the distribution volume of 18F-FDG (Fe) as a fraction
      of lung volume (Ki = Fe * k3). Regional gas fractions (fgas) were assessed by
      examining transmission scans. RESULTS: Before endotoxin administration,
      protective (vs. injurious) ventilation was associated with a higher ratio of
      partial pressure of oxygen in arterial blood to fraction of inspired oxygen
      (PaO2/FiO2) (351 +/- 117 vs. 255 +/- 74 mmHg; P < 0.01) and higher whole-lung
      fgas (0.71 +/- 0.12 vs. 0.48 +/- 0.08; P = 0.004), as well as, in dependent
      regions, lower shunt fractions. Following 2 h of endotoxemia, PaO2/FiO2 ratios
      decreased in both groups, but more so with injurious ventilation, which also
      increased the shunt fraction in dependent lung. Protective ventilation resulted
      in less nonaerated lung (20-fold; P < 0.01) and more normally aerated lung (14
      fold; P < 0.01). Ki was lower during protective (vs. injurious) ventilation,
      especially in dependent lung regions (0.0075 +/- 0.0043/min vs. 0.0157 +/-
      0.0072/min; P < 0.01). 18F-FDG phosphorylation rate (k3) was twofold higher with
      injurious ventilation and accounted for most of the between-group difference in
      Ki. Dependent regions of the protective ventilation group exhibited lower k3
      values per neutrophil than those in the injurious ventilation group (P = 0.01).
      In contrast, Fe was not affected by ventilation strategy (P = 0.52). Lung
      neutrophil counts were not different between groups, even when regional inflation
      was accounted for. CONCLUSIONS: During systemic endotoxemia, protective
      ventilation may reduce the magnitude and heterogeneity of pulmonary inflammatory
      cell metabolic activity in early lung injury and may improve gas exchange through
      its effects predominantly in dependent lung regions. Such effects are likely
      related to a reduction in the metabolic activity, but not in the number, of lung
      infiltrating neutrophils.

PMID- 23947923
TI  - Dual effects of molybdenum on mouse oocyte quality and ovarian oxidative stress.
AB  - A sub-acute toxicity test was performed to investigate the effects of molybdenum
      (Mo) on ovarian function. ICR adult female mice were exposed to Mo by free access
      to distilled water containing the Mo at 5, 10, 20, and 40 mg/L for 14 days.
      Compared to the control group, M II oocyte morphology, ovary index, and ovulation
      improved within the 5 mg/L Mo group, but were negatively affected by Mo at 40
      mg/L. Morphologically abnormal ovarian mitochondria were observed at >= 20 mg/L.
      These alterations accompanied the changes in superoxide dismutase (SOD),
      glutathione peroxidise (GPx), and malondialdehyde (MDA) levels in ovaries. In
      conclusion, Mo affects oocyte quality possibly through regulating ovarian
      oxidative stress in a dose-dependent manner. It appears that Mo may improve
      ovarian function at a suitable concentration, which might be a candidate for the
      treatment of female infertility. 

PMID- 23947922
TI  - Correlation of Wnt5a expression with histopathological grade/stage in urothelial
      carcinoma of the bladder.
AB  - BACKGROUND: Bladder cancer, including urothelial carcinoma (UC), is the most
      common malignancy of the urinary tract and the fourth most frequent cancer
      overall in men. Wnt5a, a member of the Wnt family of proteins, has been shown to
      have contradictory roles in the pathogenesis of many cancers, acting either as
      tumor suppressor or tumor promoter. The objective of this study was to
      investigate the expression and role of Wnt5a in the pathogenesis of UC and
      suggest possible clinical applications for diagnosis, prognosis and treatment.
      METHODS: We characterized the expression of Wnt5a in 33 human UC samples using
      immunohistochemistry. The samples were obtained via transurethral resection,
      immediately fixed in formalin and then embedded in paraffin. The correlation
      between Wnt5a immunoreactivity, histological grade, and pathological stage of the
      tumor was analyzed. The expression of Wnt5a mRNA as well as the effect of Wnt5a
      on cell migration was also evaluated in two UC cell lines, T24 and J82, and a
      normal urothelial cell line. RESULTS: Our immunohistochemical results revealed
      that Wnt5a staining intensity correlated positively with the histological grade
      and pathological stage of the UC. Wnt5a mRNA expression differed widely in the
      three urothelial cell lines, with high levels in one carcinoma cell line and low
      levels in the other cell line in comparison to the normal urothelial cell line.
      Migration increased in both UC cell lines in response to Wnt5a treatment.
      CONCLUSIONS: Our results show that the Wnt5a pathway may play a role in the
      pathogenesis of UC and suggest that Wnt5a may serve as an additional,
      complementary diagnostic/prognostic marker for UC. VIRTUAL SLIDE:
      http://www.diagnosticpathology.diagnomx.eu/vs/1952312091979566.

PMID- 23947924
TI  - The association of anthropometry indices with gout in Taiwanese men.
AB  - BACKGROUND: To examine the association of anthropometry indices with gout and to
      compare the performance of indices to predict gout in Taiwanese men. METHODS:
      There were 1443 male subjects aged more than 20 years who participated in the
      Nutrition and Health Survey in Taiwan (NAHSIT, 1993-1996). Anthropometric
      evaluation consisted of weight, height, hip and waist circumference (WC) with
      later body mass index (BMI), waist to height (WHtR) and waist to hip (WHR)
      estimations. We conducted 4 logistic models to determine the relationships
      between anthropometric indices and gout. Receiver operating characteristic (ROC)
      curve were used to compare the predictive performance and to identify the optimal
      cut-off points, sensitivity and specificity of these indices for gout in men.
      RESULTS: After controlling for other covariables, the adjusted odds ratios for
      the mid and top tertiles of WHtR were 2.55 (95% CI: 1.16, 5.59) and 3.01 (95% CI:
      1.13, 7.99), respectively, but no linear association was found for BMI, WHR and
      WC. In ROC curve, the greatest area under curve was 0.684 for WHtR and the cut
      off point of WHtR was 0.57. CONCLUSIONS: WHtR had a significant linear
      association with gout in Taiwanese men and was superior to BMI, WHR and WC.

PMID- 23947925
TI  - Supporting academic success:.
AB  - Formed in the Fall of 1993 in the Schools of Allied Health Professions,
      Psychology, Social Work, Education, and Nursing at the University of Wisconsin
      Milwaukee, the Supporting Academic Success Program is an educational, service
      delivery support model. The program incorporates the University's mission of
      teaching, research, and service in a collaborative effort with the Milwaukee
      Center for Independence. The Norris Health Center through Student Affairs is
      funding this project. The continuation of the program will be provided by grants
      in 1996. 

PMID- 23947926
TI  - A fieldwork model for non-traditional community practice.
AB  - The purpose of this article is to discuss a fieldwork Level II model developed by
      the College of St. Catherine in St. Paul, Minnesota for psychosocial practice.
      Fieldwork, especially psychosocial fieldwork, is undergoing significant change
      due to the shifting of occupational therapy practice and the demand for sites.
      This nontraditional group process model was developed in a shelter for the
      homeless and poor in downtown Minneapolis. The authors will trace the development
      of the model, its organization and requirements. Program results will be
      discussed including advantages and disadvantages as seen by students and faculty
      supervisors who participated in the experience. The authors believe that this
      collaborative model can develop effective student therapists who are able to work
      from a client-centered approach and are able to be flexible within a team. 

PMID- 23947927
TI  - Content revision in adolescent psychosocial occupational therapy.
AB  - A review of the literature and student feedback suggested a need for content
      revision in a course on occupational therapy with the adolescent. Unlike any
      other age group in the United States, the death rate for adolescents from
      injuries/accidents, suicide and homicide is rapidly rising (McAnarney, Kreipe, &
      Orr, 1992). High risk behaviors of substance abuse, sexual activity, and vehicle
      accidents also account for many adolescent deaths. Given the state of rapid
      change in the challenges faced by adolescents and the many diagnostic conditions
      that initially present in adolescence and are the focus of occupational therapy
      intervention, systematic and comprehensive course content revision of the
      psychosocial aspects of this adolescent course were initiated. The purpose of
      this ''classroom research'' project was to identify specific psychosocial topics
      that students perceived should be included to help them learn about providing
      occupational therapy services to the adolescent. The method used to collect data
      was a Delphi technique called the Group Instructional Feedback Technique (GIFT).
      Findings suggest that presentation of specific topics on teenage pregnancy and
      sexuality, violence, and situations in which interpersonal losses occur may
      enhance student learning and preparation for practice. The GIFT technique may
      have application to other topics in occupational therapy education. 

PMID- 23947928
TI  - Employment for individuals with mental disabilities:.
AB  - The ADA requires employers of persons with psychiatric disabilities to provide
      reasonable accommodation to overcome disability related limitations. Employers
      are bound by this requirement only when accommodation is requested. Disclosure of
      a psychiatric disability is a sensitive issue with potential negative
      consequences due to ignorance and fear. The occupational therapist has a pivotal
      role in preparing clients with psychiatric disabilities to activate ADA Title I
      Employment protections. The process of achieving accommodation and five areas for
      inclusion in Occupational Therapy practice, including preparation on when and how
      to disclose and specification of disability related limitations are described. 

PMID- 23947929
TI  - Consultation:.
AB  - In order to survive and grow as a viable mental health care profession,
      occupational therapists must learn new ways of providing service. One such way is
      using consultation theory and techniques. This article reviews pertinent
      literature about consultation and summarizes Caplan's classification for use by
      occupational therapists who are, or are considering, working in community-based
      service delivery systems such as mental health centers. The article can be used
      by those needing basic knowledge as well as by those seeking resources for
      further information. 

PMID- 23947930
TI  - Health and well-being ratings of african american adults with sickle cell
      disease:.
AB  - This paper examines Sickle Cell Disease (SCD), a chronic condition affecting
      predominantly individuals of African decent. The study describes the health and
      ratings of Adult African Americans with SCD using a Self-Evaluation of Life
      Function Scale. The majority of the respondents scored in the favorable range on
      the SELF scales suggesting good adaptation to their condition. Based on
      respondents comments more information and support would be beneficial, especially
      supportive counseling, occupational therapy intervention, and instruction to aid
      in self care management and job issues. 

PMID- 23947931
TI  - Ramsey county day treatment services:.
AB  - Ramsey County Extended Day Treatment is designed for persons with a serious and
      persistent mental illness such as major depression, schizophrenia, bipolar
      disorder or personality disorder. The uniqueness of the model is the combination
      of an intake and referral group with six levels of group psychotherapy.
      Additionally, single issue groups provide a concentrated focus on employment or
      community contribution, anger management, and peer relationships. The result is a
      well-structured, non-residential program where a client can work in a treatment
      environment based on one's ability to participate. This article describes the
      intake and referral group, outlines the six separate programs, and describes the
      use of occupational therapy and cognitive behavioral therapy throughout the
      model. 

PMID- 23947932
TI  - Three new polyketides from marine-derived fungus Aspergillus glaucus HB1-19.
AB  - Two new benzyl derivatives, aspergentisyl A (1) and aspergentisyl B (2), as well
      as one new naphthoquinone derivative, aspergiodiquinone (3), together with seven
      known prenylated benzaldehyde derivatives (4-10) were isolated from the marine
      derived fungus Aspergillus glaucus HB1-19. The structures of these compounds were
      characterized based on 1D and 2D NMR spectra analyses and comparison with those
      reported in the literature. In addition, each isolate was tested for its 1,1
      diphenyl-2-picrylhydrazyl radical-scavenging property and all these compounds
      except compound 3 exhibited strong radical-scavenging activity. 

PMID- 23947933
TI  - Generation of patient-specific induced neuronal cells using a direct
      reprogramming strategy.
AB  - Direct reprogramming of human fibroblasts into functional neurons in vitro by
      defined factors provides an invaluable resource for regenerative medicine.
      However, clinical applications must consider the risk of immune rejection, thus
      patient-specific induced neuronal cells (iNCs) may serve as an ideal source for
      autologous cell replacement. In this study, we report a robust process for
      functional neuronal cells from the patients' scalp by lentiviral gene delivery of
      Ascl1, Myt1l, and Sox2. These three-factor iNCs are similar to human neuronal
      cells in morphology, surface antigens, gene expression, and electrophysiological
      characteristics. Our findings might provide a source of patient-specific
      functional neurons for cell therapy. 

PMID- 23947935
TI  - Clinical efficacy of dofetilide for the treatment of atrial tachyarrhythmias in
      adults with congenital heart disease.
AB  - BACKGROUND: Atrial tachyarrhythmias (AT) including atrial fibrillation (AF),
      atrial flutter (AFL), and atrial tachycardia represent a clinical challenge in
      the adult with congenital heart disease (CHD). Dofetilide (D) is a rapidly
      activating delayed rectifier potassium channel (IKr) blocker effective in
      pharmacological conversion and maintenance of normal sinus rhythm in patients
      with AF and AFL. There is limited knowledge regarding the role of D in adults
      with CHD. METHODS: Safety and efficacy of D was evaluated in a consecutive group
      of thirteen adult patients (age 40 +/- 11; six women) with CHD and refractory AT.
      RESULTS: Ten patients had persistent (four AFL, one AF, and five atrial
      tachycardia) and three paroxysmal (one AF and two atrial tachycardia) AT. All
      patients were symptomatic during tachycardia, 12 patients had previously failed 2
      +/- 1 antiarrhythmic drugs. Mean systemic ventricular ejection fraction was 55 +/
      9%; baseline QRS complex duration was 129 +/- 45 ms (>120 ms in six patients).
      Patients were followed on D for 33 +/- 39 months (median 16). Among 10 patients
      with persistent AT, seven patients (70%) pharmacologically converted to sinus
      rhythm on D and three patients (30%) required direct current cardioversion. Two
      patients (15.4%) experienced complete arrhythmia suppression, and seven (53.8%)
      experienced significant clinical improvement with sporadic recurrences; average
      time to recurrence was 5.5 +/- 3.5 months. One patient developed torsade de
      pointes during loading, and the drug was discontinued. D was discontinued in five
      (38.5%) other patients due to recurrence of AT (n = 4) and renal failure (n = 1).
      Corrected QT interval (QTc) increased from 452 +/- 61 to 480 +/- 49 ms (P = .04)
      and corrected JT interval (JTc) from 323 +/- 39 to 341 +/- 33 ms (P = .09).
      CONCLUSIONS: D should be considered a pharmacologic alternative when adult
      patients with CHD develop AT. D does not depress conduction, sinus node, or
      ventricular function but needs close monitoring for potential ventricular pro
      arrhythmia.

PMID- 23947936
TI  - Prenylated and geranylated flavonoids increase production of reactive oxygen
      species in mouse macrophages but inhibit the inflammatory response.
AB  - In this study, four prenylated and geranylated flavonoids, cudraflavone B (1),
      pomiferin (2), osajin (3), and diplacone (4), were tested for their antioxidant
      and anti-inflammatory effects and to identify any potential relationships between
      chemical structure and antioxidant or anti-inflammatory properties. The selected
      flavonoids were examined in cell-free models to prove their ability to scavenge
      superoxide radicals, hydrogen peroxide, and hypochlorous acid. Further, the
      ability of the flavonoids to influence the formation of reactive oxygen species
      in the murine macrophage cell line J774.A1 was tested in the presence and absence
      of lipopolysaccharide (LPS). The ability of flavonoids to inhibit LPS-induced
      IkappaB-alpha degradation and COX-2 expression was used as a model for the
      inflammatory response. The present results indicated that the antioxidant
      activity was dependent on the chemical structure, where the catechol moiety is
      especially crucial for this effect. The most potent antioxidant activities in
      cell-free models were observed for diplacone (4), whereas cudraflavone B (1) and
      osajin (3) showed a pro-oxidant effect in J774.A1 cells. All flavonoids tested
      were able to inhibit IkappaB-alpha degradation, but only diplacone (4) also down
      regulated COX-2 expression. 

PMID- 23947937
TI  - Definition of compartment-based radical surgery in uterine cancer: modified
      radical hysterectomy in intermediate/high-risk endometrial cancer using
      peritoneal mesometrial resection (PMMR) by M Hockel translated to robotic
      surgery.
AB  - BACKGROUND: The technique of compartment-based radical hysterectomy was
      originally described by M Hockel as total mesometrial resection (TMMR) for
      standard treatment of stage I and II cervical cancer. However, with regard to the
      ontogenetically-defined compartments of tumor development (Mullerian) and lymph
      drainage (Mullerian and mesonephric), compartments at risk may also be defined
      consistently in endometrial cancer. This is the first report in the literature on
      the compartment-based surgical approach to endometrial cancer. Peritoneal
      mesometrial resection (PMMR) with therapeutic lymphadenectomy (tLNE) as an
      ontogenetic, compartment-based oncologic surgery could be beneficial for patients
      in terms of surgical radicalness as well as complication rates; it can be
      standardized for compartment-confined tumors. Supported by M Hockel, PMMR was
      translated to robotic surgery (rPMMR) and described step-by-step in comparison to
      robotic TMMR (rTMMR). METHODS: Patients (n = 42) were treated by rPMMR (n = 39)
      or extrafascial simple hysterectomy (n = 3) with/without bilateral pelvic and/or
      periaortic robotic therapeutic lymphadenectomy (rtLNE) for stage I to III
      endometrial cancer, according to International Federation of Gynecology and
      Obstetrics (FIGO) classification. Tumors were classified as intermediate/high
      risk in 22 out of 40 patients (55%) and low-risk in 18 out of 40 patients (45%),
      and two patients showed other uterine malignancies. In 11 patients, no adjuvant
      external radiotherapy was performed, but chemotherapy was applied. RESULTS: No
      transition to open surgery was necessary. There were no intraoperative
      complications. The postoperative complication rate was 12% with venous
      thromboses, (n = 2), infected pelvic lymph cyst (n = 1), transient aphasia (n =
      1) and transient dysfunction of micturition (n = 1). The mean difference in
      perioperative hemoglobin concentrations was 2.4 g/dL (+/- 1.2 g/dL) and one
      patient (2.4%) required transfusion. During follow-up (median 17 months), one
      patient experienced distant recurrence and one patient distant/regional
      recurrence of endometrial cancer (4.8%), but none developed isolated locoregional
      recurrence. There were two deaths from endometrial cancer during the observation
      period (4.8%). CONCLUSIONS: We conclude that rPMMR and rtLNE are feasible and
      safe with regard to perioperative morbidity, thus, it seems promising for the
      treatment of intermediate/high-risk endometrial cancer in terms of surgical
      radicalness and complication rates. This could be particularly beneficial for
      morbidly obese and seriously ill patients.

PMID- 23947938
TI  - Periodontal disease and oral health-related behavior as factors associated with
      preterm birth: a case-control study in south-eastern Brazil.
AB  - BACKGROUND AND OBJECTIVE: Several studies have suggested a link between
      periodontal disease and preterm birth, but the mechanism of how this occurs
      remains controversial. Therefore, this study aimed to investigate whether
      periodontal disease, defined according to two commonly used clinical definitions,
      is associated with preterm birth and to examine the association regarding oral
      health-related behaviors during pregnancy. MATERIAL AND METHODS: This case
      control study included women 18-40 years of age. Demographic and socio-economic
      data, information on current and previous pregnancies, and data on dental health
      related behaviors and periodontal clinical parameters were collected within 48 h
      postpartum. Periodontal disease was assessed according to two definitions: four
      or more teeth with at least one site showing a probing depth of >= 4 mm and
      clinical attachment level of >= 3 mm (Definition 1); or at least one site with
      probing depth and clinical attachment level of >= 4 mm (Definition 2). The chi
      square test was used to examine differences in the proportion of categorical
      variables. Bivariate analysis was performed to analyze the proportion of preterm
      births with respect to independent variables. Multiple logistic regression
      analyses were used to assess the association between periodontal disease and
      preterm birth. Odds ratios (ORs) were calculated with a 95% confidence interval
      (95% CI). RESULTS: A total of 296 postpartum women met the inclusion criteria.
      The case group included 74 women who delivered a preterm neonate (< 37 wk of
      gestation) and the control group included 222 women with deliveries at term (>=
      37 wk). Periodontal disease according to Definition 1 was not associated with
      fewer weeks of gestation (adjusted OR (OR adjusted ) = 1.62; 95% CI = 0.80-3.29;
      p = 0.178). However, a significant association was found between periodontal
      disease, according to Definition 2, and preterm birth (OR adjusted = 1.98; 95% CI
      = 1.14-3.43; p = 0.015). Increased appetite and a low number of daily
      toothbrushings were associated with preterm birth, regardless of the definition
      of periodontal disease used. CONCLUSION: Periodontal disease defined according to
      Definition 2 and unfavorable oral health-related behavior were factors associated
      with preterm birth.

PMID- 23947939
TI  - Neighborhood walkability and cardiometabolic risk factors in Australian adults:
      an observational study.
AB  - BACKGROUND: Studies repeatedly highlight associations between the built
      environment and physical activity, particularly walking. Fewer studies have
      examined associations with cardiometabolic risk factors, with associations with
      obesity inconsistent and scarce evidence examining associations with other
      cardiometabolic risk factors. We aim to investigate the association between
      neighborhood walkability and the prevalence of obesity, hypertension,
      hypercholesterolaemia, and type-2 diabetes mellitus. METHODS: Cross-sectional
      study of 5,970 adults in Western Australia. Walkability was measured objectively
      for a 1,600 m and 800 m neighborhood buffer. Logistic regression was used to
      assess associations overall and by sex, adjusting for socio-demographic factors.
      Mediation by physical activity and sedentary behavior was investigated. RESULTS:
      Individuals living in high compared with less walkable areas were less likely to
      be obese (1,600 m OR: 0.84, 95% CI: 0.7 to 1; 800 m OR: 0.75, 95% CI: 0.62 to
      0.9) and had lower odds of type-2 diabetes mellitus at the 800 m buffer (800 m
      OR: 0.69, 95% CI: 0.51 to 0.93). There was little evidence for an association
      between walkability and hypertension or hypercholesterolaemia. The only
      significant evidence of any difference in the associations in men and women was a
      stronger association with type-2 diabetes mellitus at the 800 m buffer in men.
      Associations with obesity and diabetes attenuated when additionally adjusting for
      physical activity and sedentary behavior but the overall association with obesity
      remained significant at the 800 m buffer (800 m OR: 0.78, 95% CI: 0.64 to 0.96).
      CONCLUSIONS: A protective association between neighborhood walkability and
      obesity was observed. Neighborhood walkability may also be protective of type-2
      diabetes mellitus, particularly in men. No association with hypertension or
      hypercholesterolaemia was found. This warrants further investigation. Findings
      contribute towards the accumulating evidence that city planning and policy
      related strategies aimed at creating supportive environments could play an
      important role in the prevention of chronic diseases.

PMID- 23947941
TI  - Controlled aggregation and enhanced two-photon absorption of a water-soluble
      squaraine dye with a poly(acrylic acid) template.
AB  - Controlling the aggregation behavior of organic dyes is important for
      understanding and exploring supramolecular assembly utilizing the specific
      characteristics of aggregation. Regulating J-aggregation by electrostatic
      interactions between anionic polyelectrolytes and cationic dyes has gained
      growing interest. Here, we report the formation of J-aggregates of a water
      soluble cationic squaraine dye, 4-(pyridinium-1-yl)butylbenzothiazolium squaraine
      (SQ), using poly(acrylic acid) sodium salt (PAA-Na) as a template. Electrostatic
      interactions between the PAA-Na polyelectrolyte and the cationic SQ dye enhanced
      J-aggregation; the absorbance of the resulting J-band with the polyelectrolyte
      template was much sharper than the absorbance of the J-aggregate formed using a
      high concentration of NaCl. Significantly, removal of the polyelectrolyte PPA-Na
      template by the introduction of calcium ions, which can form stronger ionic
      binding with carboxylate groups, dissociated J-aggregates, freeing the SQ
      molecules back to unaggregated or lower aggregate forms. To demonstrate the
      reversibility of the J-aggregate formation cycle, an in situ experiment was
      conducted that showed 60% reversibility of the second cycle. In addition, an
      enhancement by ca. 23 times per repeat unit of the two-photon absorption (2PA)
      cross section was observed at 920 nm for the polyelectrolyte template-SQ J
      aggregate compared to unaggregated or lower aggregate SQ. These results suggest a
      prominent role of polyelectrolyte templated SQ J-aggregation in the enhancement
      of 2PA efficiency and provide a means of modulating supramolecular assembly. 

PMID- 23947942
TI  - Development of a constructed wetland water treatment system for selenium removal:
      incorporation of an algal treatment component.
AB  - On the basis of the fact that algae have the ability to volatilize substantial
      quantities of selenium (Se), we investigated the concept of including an algal
      pretreatment unit into a constructed wetland system for the removal of Se from
      river water entering the Salton Sea. Of six different algal strains tested, the
      most effective in terms of Se volatilization and Se removal from the water column
      was a Chlorella vulgaris strain (designated Cv). Cv removed 96% of Se (supplied
      as selenate) from the microcosm water column within 72 h, with up to 61% being
      removed by volatilization to the atmosphere. X-ray absorption spectroscopy
      revealed that the major forms of Se likely to be accumulated in an algal-wetland
      system are selenomethionine, a precursor of volatile Se formation, and elemental
      Se. Our results suggest that the inclusion of an algal pretreatment unit within a
      constructed wetland water treatment system should not only enhance the efficiency
      of Se removal but also significantly reduce the risk of the buildup of ecotoxic
      forms of Se by promoting the biological volatilization of Se. 

PMID- 23947943
TI  - Multifunctional polyampholyte hydrogels with fouling resistance and protein
      conjugation capacity.
AB  - Materials that are resistant to nonspecific protein adsorption are critical in
      the biomedical community. Specifically, nonfouling implantable biomaterials are
      necessary to reduce the undesirable, but natural foreign body response. The focus
      of this investigation is to demonstrate that polyampholyte hydrogels prepared
      with equimolar quantities of positively charged [2-(acryloyloxy)ethyl]
      trimethylammonium chloride (TMA) and negatively charged 2-carboxyethyl acrylate
      (CAA) monomers are a viable solution to this problem. TMA/CAA hydrogels were
      prepared and their physical and chemical properties were characterized. The
      fouling resistance of the TMA/CAA hydrogels were assessed at varying cross-linker
      densities using enzyme-linked immunosorbant assays (ELISAs). The results clearly
      demonstrate that TMA/CAA hydrogels are resistant to nonspecific protein
      adsorption. A unique advantage of the fouling resistant TMA/CAA system is that
      bioactive proteins can be covalently attached to these materials using standard
      conjugation chemistry. This was demonstrated in this study through a combination
      of ELISA investigations and short-term cell adhesion assays. The multifunctional
      properties of the TMA/CAA polyampholyte hydrogels shown in this work clearly
      demonstrate the potential for these materials for use as tissue regeneration
      scaffolds for many biomedical applications. 

PMID- 23947944
TI  - Washout times of desflurane, sevoflurane and isoflurane from the GE Healthcare
      Aisys(r) and Avance(r), Carestation(r), and Aestiva(r) anesthesia system.
AB  - BACKGROUND/AIM: Malignant hyperthermia susceptible patients may experience a
      fatal reaction to volatile anesthetic gases. This study sought to determine the
      washout characteristics of desflurane, sevoflurane, and isoflurane from the
      Aisys(r) , Avance(r) , and Aestiva(r) anesthesia machines. (GE Healthcare,
      Madison, WI, USA). METHODS: All machines were inspected by a GE Healthcare
      engineer prior to testing. The machines were primed with desflurane 7 vol%,
      sevoflurane 2.5 vol%, and isoflurane 1.2 vol% on three separate occasions for 2 h
      each with each gas. The Aisys(r) and Avance(r) were tested with and without an
      Advanced Breathing System (ABSTM , GE Healthcare, Madison, WI, USA). The
      Aestiva(r) was tested without modification to its breathing system. Additionally,
      the Aisys was evaluated with desflurane 1.2 vol% and the Avance with a preflushed
      fresh gas line was tested with an autoclaved ABS. After priming, disposable
      components of the patient breathing system were replaced. The fresh gas flow was
      increased to 15 lpm. Gas measurements were recorded until the concentration was 4
      parts per million (p.p.m). RESULTS: The fastest median washout time was achieved
      by the Avance in 3 min or less without an ABS or with an autoclaved ABS. The
      longest median time was 35 min for the Aestiva(r) . Clearance of desflurane was
      the most time consuming for all machines. CONCLUSION: This study demonstrates
      that saturated vapor pressure and priming concentration exert a greater effect on
      washout times than gas solubility. The Aisys utilizes an electronic vaporizer
      system that may expose the breathing system to retained saturated vapor. The
      breathing systems for all machines may hinder washout of gases.

PMID- 23947945
TI  - A protocol for resuscitation of severe burn patients guided by transpulmonary
      thermodilution and lactate levels: a 3-year prospective cohort study.
AB  - INTRODUCTION: The use of urinary output and vital signs to guide initial burn
      resuscitation may lead to suboptimal resuscitation. Invasive hemodynamic
      monitoring may result in over-resuscitation. This study aimed to evaluate the
      results of a goal-directed burn resuscitation protocol that used standard
      measures of mean arterial pressure (MAP) and urine output, plus transpulmonary
      thermodilution (TPTD) and lactate levels to adjust fluid therapy to achieve a
      minimum level of preload to allow for sufficient vital organ perfusion. METHODS:
      We conducted a three-year prospective cohort study of 132 consecutive critically
      burned patients. These patients underwent resuscitation guided by MAP (>65 mmHg),
      urinary output (0.5 to 1 ml/kg), TPTD and lactate levels. Fluid therapy was
      adjusted to achieve a cardiac index (CI) >2.5 L/minute/m2 and an intrathoracic
      blood volume index (ITBVI) >600 ml/m2, and to optimize lactate levels.
      Statistical analysis was performed using mixed models. We also used Pearson or
      Spearman methods and the Mann-Whitney U-test. RESULTS: A total of 98 men and 34
      women (mean age, 48 +/- 18 years) was studied. The mean total body surface area
      (TBSA) burned was 35% +/- 22%. During the early resuscitation phase, lactate
      levels were elevated (2.58 +/- 2.05 mmol/L) and TPTD showed initial hypovolemia
      by the CI (2.68 +/- 1.06 L/minute/m2) and the ITBVI (709 +/- 254 mL/m2). At 24 to
      32 hours, the CI and lactic levels were normalized, although the ITBVI remained
      below the normal range (744 +/- 276 ml/m2). The mean fluid rate required to
      achieve protocol targets in the first 8 hours was 4.05 ml/kg/TBSA burned, which
      slightly increased in the next 16 hours. Patients with a urine output greater
      than or less than 0.5 ml/kg/hour did not show differences in heart rate, mean
      arterial pressure, CI, ITBVI or lactate levels. CONCLUSIONS: Initial hypovolemia
      may be detected by TPTD monitoring during the early resuscitation phase. This
      hypovolemia might not be reflected by blood pressure and hourly urine output. An
      adequate CI and tissue perfusion can be achieved with below-normal levels of
      preload. Early resuscitation guided by lactate levels and below-normal preload
      volume targets appears safe and avoids unnecessary fluid input.

PMID- 23947946
TI  - Systematic review of available evidence on 11 high-priced inpatient orphan drugs.
AB  - BACKGROUND: Attention for Evidence Based Medicine (EBM) is growing, but evidence
      for orphan drugs is argued to be limited and inferior. This study systematically
      reviews the available evidence on clinical effectiveness, cost-effectiveness and
      budget impact for orphan drugs. METHODS: A systematic review was performed in
      PubMed, Embase, NHS EED and HTA databases for 11 inpatient orphan drugs listed on
      the Dutch policy rule on orphan drugs. For included studies, we determined the
      type of study and various study characteristics. RESULTS: A total of 338 studies
      met all inclusion criteria. Almost all studies (96%) focused on clinical
      effectiveness of the drug. Of these studies, most studies were case studies (41%)
      or observational studies (39%). However, for all orphan diseases at least one
      experimental or quasi-experimental study was found, and a randomized clinical
      trial was available for 60% of the orphan drugs. Eight studies described the cost
      effectiveness of an orphan drug; an equal number described an orphan drug's
      budget impact. CONCLUSIONS: Despite the often heard claim that RCTs are not
      feasible for orphan drugs, we found that an RCT was available in 60% of orphan
      drugs investigated. Cost-effectiveness and budget impact analyses for orphan
      drugs are seldom published.

PMID- 23947947
TI  - Modeling and analysis of hydrodynamic and physico-chemical effects in bacterial
      deposition on surfaces.
AB  - The parallel-plate flow chamber (PFC) is often used for characterizing the
      propensity of microorganisms to attachment to surfaces. The model presented
      quantitatively analyzes the complex interplay of diffusion, convection, inertial
      lift, buoyancy, and surface forces in the PFC, which make it difficult to
      separate the surface- and microorganism-specific effects from the hydrodynamics.
      An empirical dimensionless factor K entering the boundary condition expresses
      enhancement of adhesion diffusion of microorganisms across a thin fluid layer
      adjacent to the surface by adhesion forces. The model examines the role of
      various factors (e.g., shear rate, size of bacterium, and strength of adhesion)
      on the rate of bacterial deposition. Using no adjustable parameter for strongly
      adhesive surfaces and K as the only adjustable parameter for repulsive or weakly
      adhesive surfaces, the model explains the observed decrease in deposition flux at
      high flow rates and compares reasonably with reported experimental results. The
      results suggest that the fitted value of K may be used for 'rating' the
      propensity of bacteria to deposit on surfaces and separating this from
      hydrodynamic effects.

PMID- 23947949
TI  - Ethical issues related to managed care: an in-depth discussion of an occupational
      therapy case study.
AB  - What are the ethical responsibilities of occupational therapists when managed
      care plans override their clinical judgment and deny reimbursement for needed
      assessment or therapy? Using an example from a true case, this article presents
      an analysis of the ethical problems experienced in managed care when explicit
      business goals are in conflict with the humanistic commitments of our field.
      Strategies for ethical action are recommended, including: good communication with
      the case manager, effective advocacy for the patient, consultation with ethics
      resources, and advocacy at the policy-making level. [Article copies available for
      a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address:
      getinfo@haworth.com]. 

PMID- 23947948
TI  - HIV Type 1 transmission networks among men having sex with men and heterosexuals
      in Kenya.
AB  - We performed a molecular phylogenetic study on HIV-1 polymerase sequences of men
      who have sex with men (MSM) and heterosexual patient samples in Kenya to
      characterize any observed HIV-1 transmission networks. HIV-1 polymerase sequences
      were obtained from samples in Nairobi and coastal Kenya from 84 MSM, 226 other
      men, and 364 women from 2005 to 2010. Using Bayesian phylogenetics, we tested
      whether sequences clustered by sexual orientation and geographic location. In
      addition, we used trait diffusion analyses to identify significant
      epidemiological links and to quantify the number of transmissions between risk
      groups. Finally, we compared 84 MSM sequences with all HIV-1 sequences available
      online at GenBank. Significant clustering of sequences from MSM at both coastal
      Kenya and Nairobi was found, with evidence of HIV-1 transmission between both
      locations. Although a transmission pair between a coastal MSM and woman was
      confirmed, no significant HIV-1 transmission was evident between MSM and the
      comparison population for the predominant subtype A (60%). However, a weak but
      significant link was evident when studying all subtypes together. GenBank
      comparison did not reveal other important transmission links. Our data suggest
      infrequent intermingling of MSM and heterosexual HIV-1 epidemics in Kenya.

PMID- 23947950
TI  - Managed care: survival skills for the future.
AB  - The last two decades have been a time of dramatic and consistent change in the
      way health care is delivered. The use of managed care strategies by health care
      providers impacts occupational therapy practitioners directly, yet they are often
      ill-prepared to respond to changes constructively. With adequate preparation,
      occupational therapy practitioners may not only respond to organizational change,
      but play a major role in helping to shape their organization's future. This
      article presents and defines the major managed care strategies being utilized by
      health care providers and their impacts on occupational therapy practitioners.
      The skills and strategies occupational therapy practitioners can use to
      effectively respond are presented and discussed. Suggested methods for gaining
      these skills are included. [Article copies available for a fee from The Haworth
      Document Delivery Service: 1-800-342-9678. E-mail address: getinfo@haworth.com]. 

PMID- 23947951
TI  - The impact of managed care on the practice of occupational therapy by hand
      therapists.
AB  - Current Occupational Therapy (OT) literature on managed care is limited to
      opinion or anecdotal experience. Questionnaires were mailed to 214 OTs practicing
      as hand therapists nationwide to test the null hypothesis that there was no
      difference in reimbursement or barriers to practice for OT services between
      patients enrolled in managed care organizations and those enrolled in fee-for
      service insurance plans. Statistically significant results were obtained
      indicating greater barriers to reimbursement for OT under managed care. The
      primary effect has been the increased administrative demands it places on both
      therapists and patients. [Article copies available for a fee from The Haworth
      Document Delivery Service: 1-800-342-9678. E-mail address: getinfo@haworth.com]. 

PMID- 23947952
TI  - Occupational therapy intervention for residents in a skilled nursing facility: a
      focus on atypical patients.
AB  - The 1990 implementation of the Omnibus Budget Reconciliation Act (OBRA) has
      expanded opportunities for occupational therapists to treat individuals with non
      traditional illnesses. Therapists working in skilled nursing and long term care
      can benefit from gaining an understanding of the OBRA guidelines and patient's
      rights, especially regarding restraint reduction. Occupational therapists possess
      the necessary skills to assess and treat these individuals to help maximize their
      functioning as well as improve their quality of life (Moon-Sperling & Pinson,
      1991). The premise of this article is to inform therapists about various types of
      ethical and legal intervention with atypical patients in skilled nursing
      facilities and to introduce therapists to the laws supporting provision of these
      services. [Article copies available for a fee from The Haworth Document Delivery
      Service: 1-800-342-9678. E-mail address: getinfo@haworth.com]. 

PMID- 23947953
TI  - Determination of sorption isotherm and rheological properties of lysozyme using a
      high-resolution humidity scanning QCM-D technique.
AB  - The high-resolution humidity scanning QCM-D technique enables investigation of
      hydration of soft matter films using a quartz crystal microbalance with
      dissipation monitoring (QCM-D) equipped with a humidity module. Based on a
      continuous increase of relative humidity, properties of soft matter films can be
      investigated depending on the water content of the surrounding atmosphere.
      Determination of complete water sorption isotherms is possible via analysis of
      the overtone dependence of the resonance frequencies. Rheological properties are
      monitored via measurement of the dissipation. The glass transition can be
      identified from the change of viscoelastic properties of the film reflected in
      changes of the dissipation. A high-resolution water sorption isotherm of lysozyme
      was measured and compared with results from water sorption calorimetry. Analysis
      of the rheological behavior during hydration of lysozyme films revealed the
      presence of two separate sharp transitions at the water activities 0.67 and 0.91,
      which are connected to the glass transition. In previous works, only the
      existence of a broad glass transition has been reported so far. Combining the QCM
      D data with Raman scattering data presented earlier, a new mechanism of
      isothermal glass transition in lysozyme is proposed. 

PMID- 23947954
TI  - Off-pump snare technique for congenital left atrial appendage aneurysm.
AB  - Left atrial appendage aneurysm is an extremely rare anomaly and as such has been
      rarely imaged or seen intraoperatively with very little accumulated management
      experience. The available scant published literature stresses resection on
      cardiopulmonary bypass as the safest and by far the most commonly applied
      technique. We suggest a novel alternative imaging-guided management utilising an
      off-pump tourniquet snare technique under live transoesophageal echocardiography.

PMID- 23947955
TI  - Frequency and pattern of Chinese herbal medicine prescriptions for urticaria in
      Taiwan during 2009: analysis of the national health insurance database.
AB  - BACKGROUND: Large-scale pharmaco-epidemiological studies of Chinese herbal
      medicine (CHM) for treatment of urticaria are few, even though clinical trials
      showed some CHM are effective. The purpose of this study was to explore the
      frequencies and patterns of CHM prescriptions for urticaria by analysing the
      population-based CHM database in Taiwan. METHODS: This study was linked to and
      processed through the complete traditional CHM database of the National Health
      Insurance Research Database in Taiwan during 2009. We calculated the frequencies
      and patterns of CHM prescriptions used for treatment of urticaria, of which the
      diagnosis was defined as the single ICD-9 Code of 708. Frequent itemset mining,
      as applied to data mining, was used to analyse co-prescription of CHM for
      patients with urticaria. RESULTS: There were 37,386 subjects who visited
      traditional Chinese Medicine clinics for urticaria in Taiwan during 2009 and
      received a total of 95,765 CHM prescriptions. Subjects between 18 and 35 years of
      age comprised the largest number of those treated (32.76%). In addition, women
      used CHM for urticaria more frequently than men (female:male = 1.94:1). There was
      an average of 5.54 items prescribed in the form of either individual Chinese
      herbs or a formula in a single CHM prescription for urticaria. Bai-Xian-Pi
      (Dictamnus dasycarpus Turcz) was the most commonly prescribed single Chinese herb
      while Xiao-Feng San was the most commonly prescribed Chinese herbal formula. The
      most commonly prescribed CHM drug combination was Xiao-Feng San plus Bai-Xian-Pi
      while the most commonly prescribed triple drug combination was Xiao-Feng San, Bai
      Xian-Pi, and Di-Fu Zi (Kochia scoparia). CONCLUSIONS: In view of the popularity
      of CHM such as Xiao-Feng San prescribed for the wind-heat pattern of urticaria in
      this study, a large-scale, randomized clinical trial is warranted to research
      their efficacy and safety.

PMID- 23947956
TI  - Percutaneous coronary intervention in pediatric and adolescent patients.
AB  - OBJECTIVE: Percutaneous coronary intervention (PCI) is commonly used in adult
      patients with coronary artery disease, but data on PCI in children and
      adolescents remain limited. Herein, we describe our experience with the use of
      PCI in pediatric and adolescent patients. DESIGN: This is a retrospective review.
      SETTING: The study was conducted at Mayo Clinic, Rochester, MN. PATIENTS: All
      patients <=18 years old who underwent PCI from 2004 to 2012 were included.
      INTERVENTIONS: Intravascular ultrasound and balloon angioplasty were performed in
      all patients, with subsequent stent placement in 6/7 (86%) procedures. OUTCOME
      MEASURES: Residual postintervention stenosis, early procedural morbidity and
      mortality were the outcome measures. RESULTS: Overall, seven unique PCI
      procedures were performed in five patients (four males, mean age 13.2 +/- 3.8
      years, range 8-18 years). Mean follow-up interval was 2 (0.6-5.5) years.
      Indications for the procedures included transplant coronary vasculopathy (n = 1),
      coronary dissection (n = 1), and acute coronary thrombosis/myocardial infarction
      (n = 1). Additionally, there were two patients (n = 2) who experienced coronary
      compression as a sequelae of prior heart surgery. Intravascular ultrasound and
      balloon angioplasty were performed in all patients, with subsequent stent
      placement in 6/7 (86%) procedures. A total of eight stents were placed (average
      stent diameter 3 +/- 0.5 mm), including six (75%) drug-eluting stents. The
      targeted coronary artery lesions were successfully treated in all seven
      procedures. There was no early procedural morbidity or mortality. Two patients
      were noted to have angiographic evidence of in-stent restenosis at 3 and 15
      months postdeployment, respectively, despite treatment with aspirin and
      clopidogrel. CONCLUSION: PCI in children and adolescents can be utilized to
      improve coronary blood flow in a variety of clinical situations. It may be
      particularly effective in cases of postsurgical coronary compression. Close
      angiographic follow-up is critical as these patients are at risk for in-stent
      restenosis.

PMID- 23947957
TI  - Improved efficacy and reduced toxicity by ultrasound-guided intrahepatic
      injections of helper-dependent adenoviral vector in Gunn rats.
AB  - Crigler-Najjar syndrome type I is caused by mutations of the uridine diphospho
      glucuronosyl transferase 1A1 (UGT1A1) gene resulting in life-threatening increase
      of serum bilirubin. Life-long correction of hyperbilirubinemia was previously
      shown with intravenous injection of high doses of a helper-dependent adenoviral
      (HDAd) vector expressing UGT1A1 in the Gunn rat, the animal model of Crigler
      Najjar syndrome. However, such high vector doses can activate an acute and
      potentially lethal inflammatory response with elevated serum interleukin-6 (IL
      6). To overcome this obstacle, we investigated safety and efficacy of direct
      injections of low HDAd doses delivered directly into the liver parenchyma of Gunn
      rats. Direct hepatic injections performed by either laparotomy or ultrasound
      guided percutaneous injections were compared with the same doses given by
      intravenous injections. A greater reduction of hyperbilirubinemia and increased
      conjugated bilirubin in bile were achieved with 1 * 10(11) vp/kg by direct liver
      injections compared with intravenous injections. In sharp contrast to intravenous
      injections, direct hepatic injections neither raised serum IL-6 nor resulted in
      thrombocytopenia. In conclusion, ultrasound-guided percutaneous injection of HDAd
      vectors into liver parenchyma resulted in improved hepatocyte transduction and
      reduced toxicity compared with systemic injections and is clinically attractive
      for liver-directed gene therapy of Crigler-Najjar syndrome.

PMID- 23947958
TI  - Expression of metallothionein and Nrf2 pathway genes in lung cancer and cancer
      surrounding tissues.
AB  - BACKGROUND: Nuclear factor (erythroid-derived 2)-like (Nrf)2 and metallothionein
      have been implicated in carcinogenesis. This study investigated the expression of
      Nrf2 and of Nrf2-targeted genes (NQO1 and GCLC) and the genes for the
      metallothionein (MT) isoforms (MT-1A and MT-2A) in human lung cancer and cancer
      surrounding tissues. METHODS: Surgically removed lung cancer samples (n = 80) and
      cancer-surrounding tissues (n = 38) were collected from Zunyi Medical College
      Hospital, China. Total RNA was extracted, purified, and used for real-time
      reverse transcription-PCR analysis of interested genes. RESULTS: Expression of
      the Nrf2-targed genes NQO1 and GCLC tended to be higher (30 to 60%) in lung
      cancers, but was not significantly different from that in peri-cancer tissues. By
      contrast, expression of the genes for M)-1A, MT-2A, and the metal transcription
      factor MTF-1 were three-fold to four-fold lower in lung cancers. CONCLUSION: In
      surgical samples of lung cancer, MT expression was generally downregulated,
      whereas Nrf2 expression tended to be upregulated. These changes could play an
      integral role in lung carcinogenesis.

PMID- 23947959
TI  - Asymmetric transfer hydrogenation of functionalized acetylenic ketones.
AB  - A systematic study of the asymmetric transfer hydrogenations of functionalized
      acetylenic ketones and diketones has been completed, together with a total
      synthesis of (S,S)-(-)-yashabushidiol B. In several cases, excellent
      enantioselectivities and yields were achieved. 

PMID- 23947961
TI  - How should we value future health? Was NICE right to change?

PMID- 23947962
TI  - Where are we on "risk-sharing" agreements?

PMID- 23947963
TI  - Performance-based risk-sharing arrangements-good practices for design,
      implementation, and evaluation: report of the ISPOR good practices for
      performance-based risk-sharing arrangements task force.
AB  - There is a significant and growing interest among both payers and producers of
      medical products for agreements that involve a "pay-for-performance" or "risk
      sharing" element. These payment schemes-called "performance-based risk-sharing
      arrangements" (PBRSAs)-involve a plan by which the performance of the product is
      tracked in a defined patient population over a specified period of time and the
      amount or level of reimbursement is based on the health and cost outcomes
      achieved. There has always been considerable uncertainty at product launch about
      the ultimate real-world clinical and economic performance of new products, but
      this appears to have increased in recent years. PBRSAs represent one mechanism
      for reducing this uncertainty through greater investment in evidence collection
      while a technology is used within a health care system. The objective of this
      Task Force report was to set out the standards that should be applied to "good
      practices"-both research and operational-in the use of a PBRSA, encompassing
      questions around the desirability, design, implementation, and evaluation of such
      an arrangement. This report provides practical recommendations for the
      development and application of state-of-the-art methods to be used when
      considering, using, or reviewing PBRSAs. Key findings and recommendations include
      the following. Additional evidence collection is costly, and there are numerous
      barriers to establishing viable and cost-effective PBRSAs: negotiation,
      monitoring, and evaluation costs can be substantial. For good research practice
      in PBRSAs, it is critical to match the appropriate study and research design to
      the uncertainties being addressed. Good governance processes are also essential.
      The information generated as part of PBRSAs has public good aspects, bringing
      ethical and professional obligations, which need to be considered from a policy
      perspective. The societal desirability of a particular PBRSA is fundamentally an
      issue as to whether the cost of additional data collection is justified by the
      benefits of improved resource allocation decisions afforded by the additional
      evidence generated and the accompanying reduction in uncertainty. The ex post
      evaluation of a PBRSA should, however, be a multidimensional exercise that
      assesses many aspects, including not only the impact on long-term cost
      effectiveness and whether appropriate evidence was generated but also process
      indicators, such as whether and how the evidence was used in coverage or
      reimbursement decisions, whether budget and time were appropriate, and whether
      the governance arrangements worked well. There is an important gap in the
      literature of structured ex post evaluation of PBRSAs. As an innovation in and of
      themselves, PBRSAs should also be evaluated from a long-run societal perspective
      in terms of their impact on dynamic efficiency (eliciting the optimal amount of
      innovation). 

PMID- 23947964
TI  - Value of research and value of development in early assessments of new medical
      technologies.
AB  - OBJECTIVES: In early stages of development of new medical technologies, there are
      conceptually separate but related societal decisions to be made concerning
      adoption, further development (i.e., technical improvement), and research (i.e.,
      clinical trials) of new technologies. This article presents a framework to
      simultaneously support these three decisions from a societal perspective. The
      framework is applied to the 70-gene signature, a gene-expression profile for
      breast cancer, deciding which patients should receive adjuvant systemic therapy
      after surgery. The "original" signature performed on fresh frozen tissue (70G
      FFT) could be further developed to a paraffin-based signature (70G-PAR) to reduce
      test failures. METHODS: A Markov decision model comparing the "current" guideline
      Adjuvant Online (AO), 70G-FFT, and 70G-PAR was used to simulate 20-year costs and
      outcomes in a hypothetical cohort in The Netherlands. The 70G-PAR strategy was
      based on projected data from a comparable technology. Incremental net monetary
      benefits were calculated to support the adoption decision. Expected net benefit
      of development for the population and expected net benefit of sampling were
      calculated to support the development and research decision. RESULTS: The 70G-PAR
      had the highest net monetary benefit, followed by the 70G-FFT. The population
      expected net benefit of development amounted to ?91 million over 20 years
      (assuming ?250 development costs per patient receiving the test). The expected
      net benefit of sampling amounted to ?61 million for the optimal trial (n = 4000).
      CONCLUSIONS: We presented a framework to simultaneously support adoption,
      development, and research decisions in early stages of medical technology
      development. In this case, the results indicate that there is value in both
      further development of 70G-FFT into 70G-PAR and further research.

PMID- 23947965
TI  - Cost-effectiveness of the 21-gene assay for guiding adjuvant chemotherapy
      decisions in early breast cancer.
AB  - OBJECTIVES: Adjuvant chemotherapy decisions in early breast cancer are complex.
      The 21-gene assay can potentially aid such decisions, but costs US $4175 per
      patient. Adjuvant! Online is a freely available decision aid. We evaluate the
      cost-effectiveness of using the 21-gene assay in conjunction with Adjuvant!
      Online, and of providing adjuvant chemotherapy conditional upon risk
      classification. METHODS: A probabilistic Markov decision model simulated risk
      classification, treatment, and the natural history of breast cancer in a
      hypothetical cohort of 50-year-old women with lymph node-negative, estrogen
      receptor- and/or progesterone receptor-positive, human epidermal growth factor
      receptor 2/neu-negative early breast cancer. Cost-effectiveness was considered
      from an Ontario public-payer perspective by deriving the lifetime incremental
      cost (2012 Canadian dollars) per quality-adjusted life-year (QALY) for each
      strategy, and the probability each strategy is cost-effective, assuming a
      willingness-to-pay of $50,000 per QALY. RESULTS: The 21-gene assay has an
      incremental cost per QALY in patients at low, intermediate, or high Adjuvant
      Online! risk of $22,440 (probability cost-effective 78.46%), $2,526 (99.40%), or
      $1,111 (99.82%), respectively. In patients at low (high) 21-gene assay risk,
      adjuvant chemotherapy increases (reduces) costs and worsens (improves) health
      outcomes. For patients at intermediate 21-gene assay risk and low, intermediate,
      or high Adjuvant! Online risk, chemotherapy has an incremental cost per QALY of
      $44,088 (50.59%), $1,776 (77.65%), or $1,778 (82.31%), respectively. CONCLUSIONS:
      The 21-gene assay appears cost-effective, regardless of Adjuvant! Online risk.
      Adjuvant chemotherapy appears cost-effective for patients at intermediate or high
      21-gene assay risk, although this finding is uncertain in patients at
      intermediate 21-gene assay and low Adjuvant! Online risk.

PMID- 23947966
TI  - Compensation mechanisms for lost productivity: a comparison between four European
      countries.
AB  - OBJECTIVE: Productivity costs are usually estimated by multiplying the wage with
      the period absent. This can lead to an overestimation if compensation mechanisms
      occur. Until now only Dutch data are available on the influence of compensation
      mechanisms on lost productivity, but between-country differences in frequency and
      type of compensation mechanisms can be expected. The objective of this study was
      to understand whether compensation mechanisms for days absent from paid work
      differ in type and frequency across countries and to explore whether this would
      result in between-country differences in relevant lost productivity. METHODS:
      Data from a cross-sectional survey among respondents with rheumatic disorders
      from four countries were the basis for this study. Analyses focused on
      respondents with paid employment who reported absence in the last 3 months. The
      different compensation mechanisms are described and the resulting lost
      productivity in terms of days absent was calculated with and without taking
      compensation mechanisms into account. Logistic regression analyses were performed
      to examine which variables influence compensation mechanisms leading to relevant
      lost productivity. RESULTS: The results indicate that compensation mechanisms
      occur and are relevant in all four countries. Between-country differences in the
      type and frequency of compensation mechanisms and relevant lost productivity were
      observed. The logistic regression analyses indicate that, correcting for other
      variables, this is also the case for the use of compensation mechanisms leading
      to relevant lost productivity. CONCLUSIONS: Between-country differences in
      compensation mechanisms in case of absenteeism exist and could vary to such an
      extent that foreign relevant lost productivity data should be used with caution.

PMID- 23947967
TI  - Economic analysis of the intangible impacts of informal care for people with
      Alzheimer's disease and other mental disorders.
AB  - OBJECTIVES: Valuation of the intangible impacts of informal care remains a great
      challenge for economic evaluation, especially in the framework of care recipients
      with cognitive impairment. Our main objective was to explore the influence of
      intangible impacts of caring on both informal caregivers' ability to estimate
      their willingness to pay (WTP) to be replaced and their WTP value. METHODS: We
      mapped characteristics that influence ability or inability to estimate WTP by
      using a multiple correspondence analysis. We ran a bivariate probit model with
      sample selection to further analyze the caregivers' WTP value conditional on
      their ability to estimate their WTP. RESULTS: A distinction exists between the
      opportunity costs of the caring dimension and those of the intangible costs and
      benefits of caring. Informal caregivers' ability to estimate WTP is negatively
      influenced by both intangible benefits from caring (P < 0.001) and negative
      intangible impacts of caring (P < 0.05). Caregivers' WTP value is negatively
      associated with positive intangible impacts of informal care (P < 0.01).
      CONCLUSIONS: Informal caregivers' WTP and their ability to estimate WTP are both
      influenced by intangible burden and benefit of caring. These results call into
      question the relevance of a hypothetical generalized financial compensation
      system as the optimal way to motivate caregivers to continue providing care.

PMID- 23947968
TI  - Potential cost-effectiveness of pneumococcal conjugate vaccine (PCV) in Turkey.
AB  - BACKGROUND: Pneumococcal infection is an important and preventable cause of
      morbidity and mortality. The Turkish government introduced 7-valent pneumococcal
      conjugate vaccine (PCV) into the national immunization program in 2009. This
      suggests that replacing 7-valent PCV with a higher-valent version could at least
      maintain "standard of care" if not improve it, and that it could be affordable.
      OBJECTIVES AND METHODS: The aim of this analysis was to assess the potential
      direct cost-effectiveness of 13-valent PCV in Turkey, a country with a birth
      cohort of 1.4 million, against a "no vaccine" state, against the default 7-valent
      PCV state, and against a 10-valent PCV state, using a published cohort model with
      a 5-year horizon. RESULTS AND CONCLUSIONS: The cost per life-year gained is below
      the 1 * per-capita gross domestic product threshold across large changes in key
      input parameters, indicating that the model is stable and suggesting that any PCV
      would be very cost-effective in a Turkish national pediatric immunization
      schedule.

PMID- 23947969
TI  - Transarterial chemoembolization treatment: association between multiple
      treatments, cumulative expenditures, and survival.
AB  - OBJECTIVES: To examine cumulative survival and Medicaid-paid expenses associated
      with multiple courses of transarterial chemoembolization (TACE) as primary
      treatment for hepatocellular carcinoma (HCC). METHODS: Medicare enrollees
      diagnosed with primary HCC from 2000 to 2007, ever treated with TACE, but not
      transplant/resection, followed through 2009 by using the Surveillance,
      Epidemiology and End-Results Program and linked Medicare databases. Cumulative
      all-cause/HCC-related survival was estimated by using multivariate Cox
      proportional hazards models stratified by the total number of TACE treatments.
      Multivariate weighted Cox regressions estimated the average risk of mortality
      faced with nonproportional hazards. Lin's inverse probability-weighted least
      squares regression method estimated cumulative Medicare expenditures adjusted for
      censoring and covariates. RESULTS: Of 1228 patients, 34% were stage 1, 16% stage
      2, 19% stage 3, 6% stage 4, and 26% unstaged. About 44% were aged 65 to 75 years,
      69% were men, and 72% were Caucasian. Over half (57%) of the patients received
      one course, 24% two, 11% three, and 8% four courses of TACE. One-course patients
      incurred an average $74,788 (95% confidence interval [CI] $71,890-$77,686), two
      course patients $101,126 (95% CI $94,395-$107,856), three-course patients
      $111,776 (95% CI $101,931-$121,621), and four-plus-course patients $148,878 (95%
      CI $136,346-$161,409). One-course patients lived (all-cause) an average 1.86 (95%
      CI 1.82-1.90), two-course patients 2.09 (95% CI 2.05-2.13), three-course patients
      2.81 (95% CI 2.66-2.97), and four-plus-course patients 3.06 (95% CI 2.95-3.18)
      years after diagnosis. Average risk of all-cause mortality was not significantly
      different between one/two courses or three/four-plus courses. CONCLUSIONS:
      Cumulative Medicare expenditures nearly doubled from one-course to four-plus
      course patients. On average, four-plus-course patients lived over one more year
      than did one-course patients. Physician/patient decisions should be balanced with
      consideration of efficient use of limited resources, but payer's intervention in
      physician discretion may not be important in this setting.

PMID- 23947970
TI  - Gastroprotective strategies in chronic NSAID users: a cost-effectiveness analysis
      comparing single-tablet formulations with individual components.
AB  - OBJECTIVES: To evaluate the cost-effectiveness of competing gastroprotective
      strategies, including single-tablet formulations, in the prevention of
      gastrointestinal (GI) complications in patients with chronic arthritis taking
      nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: We performed a cost
      utility analysis to compare eight gastroprotective strategies including NSAIDs,
      cyclooxygenase-2 inhibitors, proton pump inhibitors (PPIs), histamine-2 receptor
      antagonists, misoprostol, and single-tablet formulations. We derived estimates
      for outcomes and costs from medical literature. The primary outcome was
      incremental cost per quality-adjusted life-year gained. We performed sensitivity
      analyses to assess the effect of GI complications, compliance rates, and drug
      costs. RESULTS: For average-risk patients, NSAID + PPI cotherapy was most cost
      effective. The NSAID/PPI single-tablet formulation became cost-effective only
      when its price decreased from ?0.78 to ?0.56 per tablet, or when PPI compliance
      fell below 51% in the NSAID + PPI strategy. All other strategies were more costly
      and less effective. The model was highly sensitive to the GI complication risk,
      costs of PPI and NSAID/PPI single-tablet formulation, and compliance to PPI. In
      patients with a threefold higher risk of GI complications, both NSAID + PPI
      cotherapy and single-tablet formulation were cost-effective. CONCLUSIONS: NSAID +
      PPI cotherapy is the most cost-effective strategy in all patients with chronic
      arthritis irrespective of their risk for GI complications. For patients with
      increased GI risk, the NSAID/PPI single-tablet formulation is also cost
      effective.

PMID- 23947971
TI  - Health utility assessment using EQ-5D among caregivers of children with autism.
AB  - OBJECTIVES: Health utility of caregivers of children with autism was assessed by
      using the EuroQol five-dimensional (EQ-5D) questionnaire. Utility scores of
      autism caregivers were compared with norms for the general adult US population.
      Predictors of health utility were identified. METHODS: A cross-sectional online
      survey design was used. Caregivers registered with the Interactive Autism Network
      were approached for participation in the online survey. Three hundred and sixteen
      usable responses were received. Health utility among caregivers was calculated
      and compared with the US population norms by using Student's t test. Problems in
      EQ-5D questionnaire domains and utility scores were analyzed by study
      characteristics by using Kruskal-Wallis analysis of variance. Factors predicting
      health utility were identified by using ordinary least square regression.
      RESULTS: Roughly 94% of the caregivers who participated in the study were
      females. As compared to their counterparts in the general US population,
      caregivers who were aged 18 to 44 years and were females had lower utility scores
      (P < 0.001). Significant differences in utility scores were observed among
      caregivers. When compared to males, females had lower health utility. Caregivers
      of lower socioeconomic status had lower utility scores and reported more problems
      in EQ-5D questionnaire domains than did those from higher socioeconomic status.
      Caregiver burden was inversely correlated with health utility. Caregiver physical
      and mental health status, objective strain, education, and relationship with the
      care recipient were found to significantly predict health utility (adjusted R(2)
      ~57%). CONCLUSIONS: Autism caregivers had lower health utility than did the
      general adult US population. There is an immediate need to address health
      concerns among this growing population.

PMID- 23947972
TI  - Development and initial validation of the NCCN/FACT symptom index for advanced
      kidney cancer.
AB  - OBJECTIVES: There is a need for a brief symptom index for advanced kidney cancer
      that includes perspectives of both patients and clinicians and is consistent with
      the Food and Drug Administration's guidance for patient-reported outcome
      measures. This study developed and examined the preliminary reliability and
      validity of the new National Comprehensive Cancer Network/Functional Assessment
      of Cancer Therapy (FACT)-Kidney Symptom Index 19. METHODS: Fifty patients with
      advanced kidney cancer provided open-ended and survey responses ranking their
      most important symptoms. Responses were reconciled with published clinician
      reports of the most important symptoms. Ten experienced oncologists rated
      symptoms as disease- or treatment-related. Patients completed quality-of-life and
      performance status measures. RESULTS: A 19-item index was produced from symptoms
      that were rated as most important by patients or clinicians. It includes three
      subscales: disease-related symptoms (DRS), treatment side effects (TSE), and
      general function and well-being (FWB). Internal consistency was good for the full
      instrument (alpha = 0.83), the DRS subscale (alpha = 0.76), and the FWB subscale
      (alpha = 0.78) but lower for the TSE subscale (alpha = 0.59). Convergent validity
      was demonstrated through correlations with the FACT-General. Patients with
      differing performance status were distinguished by the total score (F2,47 =
      17.37; P < .0001), the DRS subscale (F2,47 = 14.22; P < .0001), and the FWB
      subscale (F2,47 = 13.40; P < .0001) but not the TSE subscale (F2,47 =1.48; P =
      0.2380). CONCLUSIONS: The National Comprehensive Cancer Network/FACT-Kidney
      Symptom Index 19 combines symptoms deemed most important by patients and
      clinicians. Preliminary evidence suggests that the total score and DRS and FWB
      subscales are reliable and valid as summary indexes. The TSE subscale may be
      least relevant given the advent of newer therapies.

PMID- 23947973
TI  - Willingness to pay for diagnostic technologies: a review of the contingent
      valuation literature.
AB  - OBJECTIVES: To understand how people value information from diagnostic
      technologies, we reviewed and analyzed published willingness-to-pay (WTP) studies
      on the topic. METHODS: We searched PubMed for English-language articles related
      to WTP for diagnostic laboratory tests published from 1985 through 2011. We
      characterized methodological differences across studies, examined individual- and
      technology-level factors associated with WTP, and summarized median WTP values
      across different diagnostic tests. RESULTS: We identified 66 relevant WTP
      studies. Half focused on oncology, while others analyzed infectious diseases (n =
      11, 16.1%) and obstetric or gynecological conditions (n = 8, 11.7%), among
      others. Most laboratory tests included in studies were biological samples/genetic
      testing (n = 44, 61.1%) or imaging tests (n = 23, 31.9%). Approximately one third
      of the analyses (n = 20, 30.3%) used discrete-choice questions to elicit WTP
      values. Higher income, education, disease severity, perceived disease risk,
      family history, and more accurate tests were in general associated with higher
      WTP values for diagnostic information. Of the 44 studies with median WTP values
      available, most reported a median WTP value below $100. The median WTP value for
      colon or colorectal cancer screening ranged from below $100 to over $1000.
      CONCLUSIONS: The contingent valuation literature in diagnostics has grown
      rapidly, and suggests that many respondents place considerable value on
      diagnostic information. There exists, however, great variation in studies with
      respect to the type of technologies and diseases assessed, respondent
      characteristics, and study methodology. The perceived value of diagnostic
      technologies is also influenced by the study design and elicitation methods.

PMID- 23947974
TI  - Does the process of deliberation change individuals' health state valuations? An
      exploratory study using the person trade-off technique.
AB  - BACKGROUND: This article explores two gaps in the health state valuation
      literature: the effect of processes and the stability of health state valuations,
      and the existence of preexisting valuations. Stability in health state valuations
      over time depends on whether preferences are considered to be preexisting (axiom
      of completeness) and therefore can be gathered reliably, or are constructed
      during consideration and debate. Under the former, changes in revealed
      preferences are evidence of poor reliability; under the latter, it is a function
      of the deliberative process. METHODS: This study explores the effect of
      deliberation on health state valuations elicited by using the person trade-off
      technique . Quantitative analysis was used to explore whether respondents changed
      their responses following deliberation and the impact of change on aggregate
      health state values. Qualitative methods were used to explore respondents' views
      on the elicitation process and the impact of deliberation on their responses.
      RESULTS: Following discussion and deliberation, 74% of the participants changed
      their person trade-off valuations and this did have an impact on the aggregate
      valuations. The qualitative analysis lends some support to the construction of
      preference assumption. CONCLUSIONS: The results from this exploratory study
      challenge the notion that individuals have preexisting health state preferences
      and call for further detailed research in this area. Furthermore, it raises
      concerns over current practices around preference elicitation exercises, which
      have tended to be carried out as a solitary exercise without allowing time for
      respondents to reflect and deliberate on their decisions.

PMID- 23947975
TI  - Italian population-based values of EQ-5D health states.
AB  - OBJECTIVE: To estimate a value set for the calculation of Italian-specific
      quality-adjusted life years (QALYs), based on preferences elicited on EuroQol
      five-dimensional (EQ-5D) questionnaire health states using the time trade-off
      technique. METHODS: The revised standard Measurement and Valuation of Health
      protocol was followed. Twenty-five health states, divided into three groups and
      given to 450 subjects, were selected to obtain 300 observations per state.
      Subjects aged 18 to 75 years were recruited to be representative of the Italian
      general adult population for age, sex, and geographical distribution. To improve
      efficiency, face-to-face interviews were conducted by using the Computer Assisted
      Personal Interviewing approach. Several random effects regression models were
      tested to predict the full set of EQ-5D questionnaire health states. Model
      selection was based on logical consistency of the estimates, sign and magnitude
      of the regression coefficients, goodness of fit, and parsimony. RESULTS: The
      model that satisfied the criteria of logical consistency and was more efficient
      includes 10 main effect dummy variables for the EQ-5D questionnaire domain levels
      and the D1 interaction term, which accounts for the number of dimensions at
      levels 2 or 3 beyond the first. This model has an R(2) of 0.389 and a mean
      absolute error of 0.03, which are comparable to or better than those of models
      used in other countries. The utility estimates after state 11111 range from 0.92
      (21111) to -0.38 (33333). Italian utility estimates are higher than those
      estimated in the United Kingdom and Spain and used so far to assess QALYs and
      conduct cost-utility evaluations in Italy. CONCLUSIONS: A specific value set is
      now available to calculate QALYs for the conduction of health economic studies
      targeted at the Italian health care system.

PMID- 23947976
TI  - Association between health-related quality of life and body mass after adjustable
      gastric banding: a nonlinear approach.
AB  - OBJECTIVE: To estimate the relationship between health utilities and body mass
      index (BMI) among a cohort of obese patients who underwent laparoscopic
      adjustable gastric banding (LAGB). METHODS: We used a cross-sectional survey to
      ascertain demographic, clinical, and health utility data from patients who had
      undergone LAGB in Washington State from 2004 to 2010. The EuroQol five
      dimensional (EQ-5D) questionnaire was used for health utility estimation. We
      calculated adjusted EQ-5D questionnaire indices across BMI categories by using a
      two-part model. We also used logistic regression to examine the relationship
      between BMI and the likelihood of reporting problems on each of the EQ-5D
      questionnaire dimension. RESULTS: Data were obtained from 790 subjects. The mean
      adjusted EQ-5D questionnaire indices for all obese BMI categories were
      significantly lower than those in the normal weight category. The relationship
      between BMI and EQ-5D questionnaire indices was nonlinear. Respondents classified
      as morbidly obese II (BMI > 50 kg/m(2)) had the greatest decrement (-0.15, 95%
      confidence interval -0.28 to -0.01) in EQ-5D questionnaire indices. The
      association between EQ-5D questionnaire indices and BMI at the time of the survey
      was weaker after adjusting for weight loss after LAGB. Respondents with higher
      BMI were more likely to report having problems in the mobility, usual/activity,
      pain/discomfort, and anxiety/depression dimensions (trend test, P < 0.05), but
      not for the self-care dimension (trend test, P = 0.08). CONCLUSIONS: The EQ-5D
      questionnaire has a negative and nonlinear relationship with BMI for obese
      patients who had LAGB. The relationship is confounded by weight loss. Within the
      EQ-5D questionnaire dimensions, patients are more likely to report having
      problems in the mobility, usual/activity, pain/discomfort, and anxiety/depression
      dimensions in higher BMI categories, but not in the self-care dimension.

PMID- 23947977
TI  - Reviewing the evidence to inform the population of cost-effectiveness models
      within health technology assessments.
AB  - OBJECTIVES: Health technology assessments (HTAs) typically require the
      development of a cost-effectiveness model, which necessitates the identification,
      selection, and use of other types of information beyond clinical effectiveness
      evidence to populate the model parameters. The reviewing activity associated with
      model development should be transparent and reproducible but can result in a
      tension between being both timely and systematic. Little procedural guidance
      exists in this area. The purpose of this article was to provide guidance,
      informed by focus groups, on what might constitute a systematic and transparent
      approach to reviewing information to populate model parameters. METHODS: A focus
      group series was held with HTA experts in the United Kingdom including systematic
      reviewers, information specialists, and health economic modelers to explore these
      issues. Framework analysis was used to analyze the qualitative data elicited
      during focus groups. RESULTS: Suggestions included the use of rapid reviewing
      methods and the need to consider the trade-off between relevance and quality. The
      need for transparency in the reporting of review methods was emphasized. It was
      suggested that additional attention should be given to the reporting of
      parameters deemed to be more important to the model or where the preferred
      decision regarding the choice of evidence is equivocal. DISCUSSION: These
      recommendations form part of a Technical Support Document produced for the
      National Institute for Health and Clinical Excellence Decision Support Unit in
      the United Kingdom. It is intended that these recommendations will help to ensure
      a more systematic, transparent, and reproducible process for the review of model
      parameters within HTA.

PMID- 23947978
TI  - Updating the Canadian hemophilia outcomes-kids life assessment tool (CHO-KLAT
      Version2.0).
AB  - OBJECTIVES: Hemophilia is an X-chromosome-linked disorder associated with
      recurrent bleeding into muscles and joints, leading to pain and limitations in
      physical function that may diminish quality of life. The Canadian Hemophilia
      Outcomes-Kids Life Assessment Tool (CHO-KLAT) is a disease-specific measure of
      quality of life that was recently revised to facilitate cross-cultural
      adaptation. This study assessed the validity and reliability of version 2.0 of
      the CHO-KLAT (CHO-KLAT2.0). METHODS: Content validity was assessed via detailed
      cognitive debriefing to confirm that Canadian boys understood the CHO-KLAT2.0.
      The measurement properties of the CHO-KLAT2.0 were assessed in comparison to
      those of the PedsQL, the Haemo-QoL, and two global ratings. Most children
      completed the CHO-KLAT2.0 a second time to assess test-retest reliability.
      RESULTS: Cognitive debriefing was completed with 12 boys (age 8.6-17.8 years) and
      9 of their parents and resulted in no substantive changes. Sixty boys (mean age
      11.8 years) participated in the validation phase, which showed a mean CHO-KLAT2.0
      score of 75.4+/-12.0, strong correlations with the PedsQL (r = 0.62, P<0.001) and
      Haemo-QoL (r = 0.64, P<0.001), and moderate correlations with global ratings of
      hemophilia bother (rho =-0.39, P = 0.002) and health (rho =-0.47, P = 0.0002).
      Test-retest concordance was better among parents (0.79) than among boys (0.63).
      CONCLUSIONS: This study establishes the measurement properties of the CHO
      KLAT2.0. The summary scores are very similar to those from the original
      development study, and thus, these have not been affected by the revisions. These
      results provide reference standards for comparing data from other countries to
      the Canadian experience and to estimate sample sizes for future clinical trials.

PMID- 23947979
TI  - Which is more valuable, longer survival or better quality of life? Israeli
      oncologists' and family physicians' attitudes toward the relative value of new
      cancer and congestive heart failure interventions.
AB  - OBJECTIVES: We determined how Israeli oncologists and family physicians value
      life-prolongation versus quality-of-life (QOL)-enhancing outcomes attributable to
      cancer and congestive heart failure interventions. METHODS: We presented
      physicians with two scenarios involving a hypothetical patient with metastatic
      cancer expected to survive 12 months with current treatment. In a life
      prolongation scenario, we suggested that a new treatment increases survival at an
      incremental cost of $50,000 over the standard of care. Participants were asked
      what minimum improvement in median survival the new therapy would need to provide
      for them to recommend it over the standard of care. In the QOL-enhancing
      scenario, we asked the maximum willingness to pay for an intervention that leads
      to the same survival as the standard treatment, but increases patient's QOL from
      50 to 75 (on a 0-100 scale). We replicated these scenarios by substituting a
      patient with congestive heart failure instead of metastatic cancer. We derived
      the incremental cost-effectiveness ratio per quality-adjusted life-year (QALY)
      gained threshold implied by each response. RESULTS: In the life-prolongation
      scenario, the cost-effectiveness thresholds implied by oncologists were
      $150,000/QALY and $100,000/QALY for cancer and CHF, respectively. Cost
      effectiveness thresholds implied by family physicians were $50,000/QALY
      regardless of the disease type. Willingness to pay for the QOL-enhancing
      scenarios was $60,000/QALY and did not differ by physicians' specialty or
      disease. CONCLUSIONS: Our findings suggest that family physicians value life
      prolonging and QOL-enhancing interventions roughly equally, while oncologists
      value interventions that extend survival more highly than those that improve only
      QOL. These findings may have important implications for coverage and
      reimbursement decisions of new technologies.

PMID- 23947980
TI  - Validating and improving the reliability of the EORTC qlq-c30 using a
      multidimensional Rasch model.
AB  - OBJECTIVE: The reliability and validity of the European Organization for Research
      and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) has not
      been examined while taking into account the correlation between subscales. The
      reliability of the EORTC QLQ-C30 subscales is modest, thus limiting their utility
      in both clinical and research settings. The purpose of this study was to validate
      the factor structure of multiple-item subscales of the EORTC QLQ-C30 and to
      improve their reliability by means of an item response analysis by using the
      multidimensional partial credit model. METHODS: A total of 2295 patients with
      complete data were used for the analysis. One- and nine-dimensional partial
      credit models were used to fit the data to validate the construct validity of the
      multiple-item subscales of the QLQ-C30. RESULTS: The model comparison showed that
      the nine-dimensional factor structure of multiple-item subscales was
      satisfactory. The multidimensional partial credit model fit data of the multiple
      item subscales of the QLQ-C30 reasonably well. The estimated test reliabilities
      of each domain obtained from the multidimensional approach were higher than those
      obtained from the unidimensional approach. CONCLUSIONS: The constructs
      represented by the multiple-item subscales of the QLQ-C30 were validated. The
      improved reliability of the multiple-item subscales of the QLQ-C30 under the
      multidimensional approach can facilitate their applications in clinical and
      research settings.

PMID- 23947981
TI  - How should we deal with patient heterogeneity in economic evaluation: a
      systematic review of national pharmacoeconomic guidelines.
AB  - OBJECTIVE: To review and analyze recommendations from national pharmacoeconomic
      guidelines with regard to acknowledging patient heterogeneity in economic
      evaluations. METHODS: National pharmacoeconomic guidelines were obtained through
      the ISPOR Web site. Guidance was extracted by using a developed data extraction
      sheet. Extracted data were divided into subcategories on the basis of consensus
      meetings. RESULTS: Of the 26 included guidelines, 20 (77%) advised to identify
      patient heterogeneity. Most guidelines (77%) provided general methodological
      advice to acknowledge patient heterogeneity, including justifications for
      distinguishing subgroups (65%), prespecification of subgroups (42%), or
      methodology to acknowledge patient heterogeneity (77%). Stratified analysis of
      cost-effectiveness was most commonly advised (20 guidelines; 77%); however,
      guidance on the specific application of methods was scarce (9 guidelines; 34%)
      and generally limited if provided. Guidance to present patient heterogeneity was
      provided by 15 guidelines (58%), most prominently to describe the definition
      (31%) and justification (31%) of subgroups. CONCLUSIONS: The majority of national
      pharmacoeconomic guidelines provide guidance on acknowledging patient
      heterogeneity in economic evaluations. However, because guidance is mostly not
      specific, its usefulness is limited. This may reflect that the importance of
      acknowledging patient heterogeneity is usually recognized while there is a lack
      of consensus on specific methods to acknowledge patient heterogeneity. We advise
      the further development of national pharmacoeconomic guidelines to provide
      specific guidance on the identification of patient heterogeneity, methods to
      acknowledge it, and presenting the results. We present a checklist that can
      assist in formulating these recommendations. This could facilitate the systematic
      and transparent handling of patient heterogeneity in economic evaluations
      worldwide.

PMID- 23947982
TI  - Impact of interventions on medication adherence and blood pressure control in
      patients with essential hypertension: a systematic review by the ISPOR medication
      adherence and persistence special interest group.
AB  - OBJECTIVES: To systematically review the evidence on the impact of interventions
      to improve medication adherence in adults prescribed antihypertensive
      medications. METHODS: An electronic search was undertaken of articles published
      between 1979 and 2009, without language restriction, that focused on
      interventions to improve antihypertensive medication adherence among patients
      (>=18 years) with essential hypertension. Studies must have measured adherence as
      an outcome of the intervention. We followed standard guidelines for the conduct
      and reporting of the review and conducted a narrative synthesis of reported data.
      RESULTS: Ninety-seven articles were identified for inclusion; 35 (35 of 97,
      36.1%) examined interventions to directly improve medication adherence, and the
      majority (58 of 97, 59.8%) were randomized controlled trials. Thirty-four (34 of
      97, 35.1%) studies reported a statistically significant improvement in medication
      adherence. DISCUSSION/CONCLUSIONS: Interventions aimed at improving patients'
      knowledge of medications possess the greatest potential clinical value in
      improving adherence with antihypertensive therapy. However, we identified several
      limitations of these studies, and advise future researchers to focus on using
      validated adherence measures, well-designed randomized controlled trials with
      relevant adherence and clinical outcomes, and guidelines on the appropriate
      design and analysis of adherence research.

PMID- 23947983
TI  - Efficacy, patient-reported outcomes (PROs), and tolerability of the changing
      therapeutic landscape in patients with metastatic prostate cancer (MPC): a
      systematic literature review.
AB  - OBJECTIVE: New therapies have attempted to improve on efficacy outcomes observed
      with docetaxel in patients with metastatic prostate cancer (MPC) who are hormone
      therapy refractory or castration-resistant. In addition to the efficacy, patient
      reported outcomes (PROs) and tolerability need to be assessed to define treatment
      benefit, as PROs measure the patient's subjective experience and can be
      correlated with hard outcomes. The main objective of this study was to evaluate
      the survival benefit of new therapies and secondary efficacy-related outcomes.
      Assessment of the number of studies reporting PROs and tolerability was also
      conducted. METHODS: A predefined search strategy was conducted on major
      academic/governmental databases and conference proceedings (2007-2011). Exclusion
      criteria were applied. RESULTS: Of 77 studies identified, 26 (34%) evaluated
      survival as an end point; 14 (18%) assessed PROs/tolerability. In chemotherapy
      naive patients (no/minimal symptoms), median overall survival (OS) was 26 months
      for sipuleucel-T. In relapsed patients, the survival benefit of
      cabazitaxel/abiraterone was 15 months and that of enzalutamide was 18 months.
      Denosumab prolonged time to first on-study skeletal-related event (20.7 months
      denosumab, 17.1 months zoledronic acid; P = 0.0002, noninferiority; P = 0.008,
      superiority). Similar benefit was documented with radium-223, a new bone-targeted
      alpha-particle-emitting radiopharmaceutical. Radium-223 also significantly
      improved the OS (two-sided P = 0.00185). Specific to PROs, they were incorporated
      primarily as secondary end points, and improvements in pain response (most
      commonly evaluated) were variable among the agents. Last, the therapies were
      associated with unique toxicities requiring careful consideration. CONCLUSIONS:
      The results of this review demonstrate that the therapeutic landscape of MPC has
      changed dramatically and many therapies in MPC now show OS improvements of about
      4 months in the postdocetaxel setting.

PMID- 23947984
TI  - A systematic literature review of psychosocial and behavioral factors associated
      with initial medication adherence: a report of the ISPOR medication adherence &
      persistence special interest group.
AB  - OBJECTIVES: Numerous factors influencing medication adherence in chronically ill
      patients are well documented, but the paucity of studies concerning initial
      treatment course experiences represents a significant knowledge gap. As
      interventions targeting this crucial first phase can affect long-term adherence
      and outcomes, an international panel conducted a systematic literature review
      targeting behavioral or psychosocial risk factors. METHODS: Eligible published
      articles presenting primary data from 1966 to 2011 were abstracted by independent
      reviewers through a validated quality instrument, documenting terminology,
      methodological approaches, and factors associated with initial adherence
      problems. RESULTS: We identified 865 potentially relevant publications; on full
      review, 24 met eligibility criteria. The mean Nichol quality score was 47.2
      (range 19-74), with excellent reviewer concordance (0.966, P < 0.01). The most
      prevalent pharmacotherapy terminology was initial, primary, or first-fill
      adherence. Articles described the following factors commonly associated with
      initial nonadherence: patient characteristics (n = 16), medication class (n =
      12), physical comorbidities (n = 12), pharmacy co-payments or medication costs (n
      = 12), health beliefs and provider communication (n = 5), and other issues. Few
      studies reported health system factors, such as pharmacy information, prescribing
      provider licensure, or nonpatient dynamics. CONCLUSIONS: Several methodological
      challenges synthesizing the findings were observed. Despite implications for
      continued medication adherence and clinical outcomes, relatively few articles
      directly examined issues associated with initial adherence. Notwithstanding this
      lack of information, many observed factors associated with nonadherence are
      amenable to potential interventions, establishing a solid foundation for
      appropriate ongoing behaviors. Besides clarifying definitions and methodology,
      future research should continue investigating initial prescriptions, treatment
      barriers, and organizational efforts to promote better long-term adherence.

PMID- 23947985
TI  - Deciding which drugs get onto the formulary: a value-based approach.
AB  - OBJECTIVES: Hospitals, physicians, payers, and patients face economic and ethical
      decisions about the use of biotechnology drugs, commonly called specialty
      medications. These often target a small population, have data based on smaller
      clinical trials, are expensive, and may have questionable advantage. This is a
      result of how the Food and Drug Administration (FDA) approves medications, which
      is based only on safety and efficacy. Cancer drugs, once approved by the FDA,
      regardless of cost or value must be covered by Medicare. Some states have laws
      requiring additional coverage as well. All of this has created an unintended
      consequence: It has driven up costs with questionable evidence to support the
      medication's value, placing patients, payers, and providers in an ethical
      conflict. In this new era of health care transformation, health care leaders must
      focus on creating value to support a sustainable health system. Christiana Care
      Health System's Value Institute has designed a new model to evaluate specialty
      medications, using value as its main criterion. METHODS: This article describes
      the process and outcomes using a new value model for evaluating specialty
      medications for a hospital formulary. It also introduces a new criterion of
      evaluation entitled "Societal Benefit" that provides a rating on quality- of-life
      issues. With measurable factors of efficacy, risk, cost, and quality-of-life
      concerns, our methodology provides a more balanced approach in the evaluation of
      specialty medications. RESULTS: Specialty medications are the fastest growing
      segment of drug expense, and it is hard to understand how these medications will
      be sustainable under health care reforms. Unlike other countries, the United
      States has no national agency providing cost-effectiveness review; review occurs,
      if at all, at a local level. Laws governing Medicare and most private insurers'
      coverage of FDA-approved medication and some clinical quality standards conflict
      with cost-effectiveness, making this type of review difficult. Finally, because
      these medications affect the health system as a whole, it is a great example to
      begin to support health care reform. CONCLUSIONS: Hospitals need to challenge the
      value of specialty medication. Although our model will continue to evolve, value
      is now our central consideration when selecting specialty medications to be added
      to the formulary. We share this experience to encourage other hospitals to design
      their own approach to this vital issue.

PMID- 23947986
TI  - Failure in developing high-level visual functions after occipitoparietal lesions
      at an early age: a case study.
AB  - Previous functional magnetic resonance imaging (fMRI) studies have identified
      several regions in the ventral visual pathway that are specialized for processing
      faces, words and general objects. However, little is known about the origin of
      the functional selectivity of these regions. Here, we reported a pediatric
      patient who suffered a left occipitoparietal lesion in the first year after birth
      from a subdural hematoma. After the hematoma was removed at the age of six, the
      hemianopia in the right visual field was alleviated, and no obvious deficits in
      low-level vision were observed in the patient at the age of twelve. In line with
      the behavioral observations, meridian mappings with fMRI showed that the early
      visual cortex of the left hemisphere was significantly activated, which was
      similar to that of the intact right hemisphere. However, the left ventral
      temporal cortex failed to show selective responses for faces, words and objects,
      which were in contrast to the normal selective responses for these objects in the
      right counterpart. Therefore, it is likely that the development of object
      selectivity in the ventral temporal cortex depends on visual inputs from the
      early visual cortex at an early age. 

PMID- 23947987
TI  - Abiotic and biotic factors that influence the bioavailability of gold
      nanoparticles to aquatic macrophytes.
AB  - This research identified and characterized factors that influenced nanomaterial
      bioavailability to three aquatic plants: Azolla caroliniana Willd, Egeria densa
      Planch., and Myriophyllum simulans Orch. Plants were exposed to 4-, 18-, and 30
      nm gold nanoparticles. Uptake was influenced by nanoparticle size, the presence
      of roots on the plant, and dissolved organic carbon in the media. Statistical
      analysis of the data also revealed that particle uptake was influenced by a 4-way
      (plant species, plant roots, particle size, and dissolved organic carbon)
      interaction suggesting nanoparticle bioavailability was a complex result of
      multiple parameters. Size and species dependent absorption was observed that was
      dependent on the presence of roots and nanoparticle size. The presence of
      dissolved organic carbon was found to associate with 4- and 18-nm gold
      nanoparticles in suspension and form a nanoparticle/organic matter complex that
      resulted in (1) minimized particle aggregation and (2) a decrease of nanoparticle
      absorption by the aquatic plants. The same effect was not observed with the 30-nm
      nanoparticle treatment. These results indicate that multiple factors, both biotic
      and abiotic, must be taken into account when predicting bioavailability of
      nanomaterials to aquatic plants. 

PMID- 23947988
TI  - The urology match as a prisoner's dilemma: a game theory perspective.
AB  - OBJECTIVE: To investigate the potential inefficiency in allowing urology
      residency applicants the ability to apply to an unlimited number of programs, and
      to study whether an application limit would lead toward a more efficient urology
      match. MATERIALS AND METHODS: Eleven-year data from the American Urological
      Association were assessed to investigate whether an increase in the yearly mean
      number of submitted applications was associated with an increase in the yearly
      mean number of interviews attended or yearly match rate. A match model resembling
      the current match, except for an application limit, was created to assess the
      financial and time savings of an application limit. RESULTS: There was no
      statistically significant relationship between the mean number of submitted
      applications per applicant with the mean number of interviews an applicant
      attends (P = .545), match rate (P = .383), or match rate when adjusted to account
      for additional positions becoming available (P = .100). The cost and time savings
      of a urology residency match that features an application limit in our model are
      substantial (up to $575,000 for applicants collectively and 1639 minutes per
      program director). CONCLUSION: Allowing urology residency applicants the ability
      to submit an unlimited number of applications is inefficient. A urology residency
      match program featuring an application limit would be more financially practical
      for applicants and engender significant time savings for program directors.

PMID- 23947989
TI  - The frequency of tumor-infiltrating Tie-2-expressing monocytes in renal cell
      carcinoma: its relationship to angiogenesis and progression.
AB  - OBJECTIVE: To examine the frequency of tumor-infiltrating Tie-2-expressing
      monocytes (TEMs) in renal cell carcinoma (RCC) and its association with
      microvessel density (MVD) and other clinical-pathologic features. MATERIALS AND
      METHODS: This study enrolled 65 consecutive patients with RCC treated with
      radical nephrectomy. The frequency of tumor-infiltrating TEMs, which was defined
      as CD14(+) Tie-2(+) cells, was assessed using flow cytometry. MVD was measured by
      immunohistochemistry using anti-CD34 antibody. The association between
      clinicopathologic parameters, MVD, and the frequency of tumor-infiltrating TEMs
      in RCC was assessed. RESULTS: High frequency of tumor-infiltrating TEMs was
      significantly associated with advanced stage (P = .018), positive lymph nodes (P
      = .013), high grade (P = .019), and metastases (P = .006). Correlation analysis
      revealed that the frequency of TEMs was positively correlated with MVD.
      CONCLUSION: Our findings revealed a significant association between prognostic
      tumor features, MVD, and the frequency of tumor-infiltrating TEMs in RCC and
      indicated that TEMs may play an important role in angiogenesis and progression of
      RCC.

PMID- 23947990
TI  - Acute graft dysfunction after living-related renal transplant.

PMID- 23947992
TI  - Editorial comment.

PMID- 23947994
TI  - [Black esophagus].
AB  - INTRODUCTION: Acute necrosis of the esophagus, frequently referred to as black
      esophagus is a rare clinical entity. CASE REPORT: We here report a case of an
      acute necrosis of the esophagus secondary to hemodynamic compromise after total
      hip replacement. Past medical history of our 72-year-old patient was remarkable
      for coronary heart disease, obstructive arteriopathy of the lower limbs, diabetes
      mellitus and hypertension. He was referred for hematemesis and epigastric pain
      one day after the surgical intervention was performed. Gastric endoscopy showed
      necrosis of the esophagus. Treatment consisted on intravenous proton pump
      inhibitor, parenteral renutrition, and red blood cell transfusion. Fours days
      later, endoscopy found complete disappearance of necrosis. CONCLUSION: Black
      esophagus develops in debilitated patients during hypoperfusion and stress. The
      outcome is usually favourable in the absence of comorbidities.

PMID- 23947995
TI  - [Syphilis in Nantes tertiary care hospital between 2000 and 2010: a case series
      of 36 hospitalized patients].
AB  - PURPOSE: Syphilis infection increase has been observed since the early 2000s. The
      medical records of patients hospitalized for syphilis at the tertiary care
      hospital of Nantes between 2000 and 2010 were retrospectively reviewed. METHODS:
      Cases were selected on the basis of serological database of the laboratory of
      bacteriology and extraction from the PMIS. Syphilis cases were defined by both
      positive TPHA and VDRL tests. RESULTS: The number of positive serology testing
      was increased eightfold within ten years. Among the 36 patients with syphilis
      hospitalized cases, 97% were male, aged 17 to 75 years. Eighteen were HIV
      infected patients. Among them, 94% were homosexuals and 67% had a history of
      sexually transmitted infections. The mean time between symptoms and diagnosis was
      significantly higher in non HIV-infected patients. Clinical forms of syphilis
      were cutaneomucous secondary syphilis with frequent systemic symptoms for 33%,
      neurosyphilis, including frequent uveitis for 50%, and gummatous tertiary
      syphilis involving bones for one patient. Secondary syphilis cases were treated
      with one to three doses of benzathine penicillin G. Late syphilis and cases of
      neurosyphilis were treated with penicillin G or ceftriaxone. Neurosensory
      sequelae accounted for 39% neurosyphilis cases. CONCLUSION: This study highlights
      the incidence increase of syphilis cases in France, frequent poor prognosis of
      neurosyphilis cases, and diagnosis difficulties, particularly in non HIV-infected
      patients. This emphasizes the broader use of syphilis serology for compatible
      medical situations.

PMID- 23947996
TI  - Airway obstruction in children with cerebral palsy: need for tracheostomy?
AB  - OBJECTIVE: To examine the progress of the airway obstruction over time in
      children with cerebral palsy (CP) and the timing of any interventions. METHODS:
      The medical notes of patients with CP younger than 16 years admitted with airway
      obstruction to a tertiary referral Pediatric Otolaryngology Center from 2006 to
      2012 were retrospectively reviewed. The gender, age of referral, co-morbidities,
      type of surgical intervention and age this was performed and the time interval
      between sequential surgeries were documented. RESULTS: Fifteen children with CP
      and airway obstruction were admitted, eight boys and seven girls with an average
      age of referral 8 years (range 3-13.3 years). Adenotonsillectomy was performed in
      11/15 patients at a mean age of 9.1 years (range 4.5-14 years). Tracheostomy was
      performed in 8/15 children at an average age of 11.6 years (range 7.5-15 years).
      Seven out of 11 patients having undergone adenotonsillectomy, required
      tracheostomy after an average time interval of 1.9 years (range 0.5-3.5 years).
      Tracheostomy was performed in 80% of referred patients with CP older than 10
      years, while surgical intervention was uncommon in children younger than 5 years.
      There was a statistically significant correlation between the age of the children
      and the performance of a tracheostomy (Pearson's correlation coefficient 0.68, p
      = 0.005). CONCLUSIONS: The severity of the airway obstruction in children with CP
      tends to increase with age. We postulate that this increase results from
      worsening hypotonia of pharyngeal musculature. Children with CP and severe upper
      airway obstruction are likely to require tracheostomy as they grow older.

PMID- 23947997
TI  - The price of doing pediatric sinus procedures (a look at cost).
AB  - OBJECTIVE: Display the cost savings of minimal sterile covers and preparatory
      time while still maintaining optimal outcomes for sinus procedures. In-office non
      sterile endoscopic sinus procedures have not shown a difference in infections and
      complications. Institutions continue to employ more "traditional" sterile
      preparation with similar procedures in the operating room. Multiple studies have
      also shown no significant difference in postoperative course when preoperative
      antibiotics are administered for sinus procedures. METHODS: Endoscopic sinus
      procedures were selected (58 patients) to analyze itemized sterile costs. Drapes,
      gloves, gowns, and antibiotics were then tallied and compared to the same items
      for cochlear implants (14 procedures). The "sterile-prep" time was also analyzed
      and compared between the two procedures. Cost difference was analyzed. RESULTS:
      Comparing the supplies used for sinus procedures (56) and cochlear implants, our
      average sinus cost was $10.19, compared to $34.64, with a difference of $24.45.
      This equated to a savings of $1418.00 in sinus procedure supplies that year. The
      difference in draping and scrubbing time showed a difference of 20 min between
      groups, equaling a value of $1760 difference/case. This calculated to a savings
      of $10,2080 for sinus operating room time. There was no difference in patient
      outcomes with this surgical preparatory approach. CONCLUSION: Our analysis showed
      a large cost savings over a fiscal year in operative time and supplies. This did
      not compromise any patient outcomes given the already non-sterile nature of
      endoscopic sinus surgery. This practice can be adopted to greatly enhance
      efficiency without sacrificing surgical results.

PMID- 23947998
TI  - Tightening the reins on nursing practice.

PMID- 23947999
TI  - Peer victimization and sexual risk differences between lesbian, gay, bisexual,
      transgender, or questioning and nontransgender heterosexual youths in grades 7
      12.
AB  - OBJECTIVES: Before and after accounting for peer victimization, we estimated
      sexual risk disparities between students who self-identified as lesbian, gay,
      bisexual, transgender, or questioning (LGBTQ) and students who self-identified as
      nontransgender heterosexual. METHODS: Students in grades 7 through 12 in Dane
      County, Wisconsin, were given the Web-administered Dane County Youth Assessment.
      One set of analyses was based on a sample that included 11 337 students.
      Subsequent analyses were based on a sample from which we screened out students
      who may not have been responding to survey items truthfully. Various multilevel
      modeling and propensity-score-matching strategies ensured robustness of the
      results, examined disparities at lower and higher victimization rates, and
      explored heterogeneity among LGBTQ-identified youths. Finally, propensity-score
      matching strategies estimated LGBTQ-heterosexual disparities in 2 matched
      samples: a sample that reported higher victimization and one that reported lower
      victimization. RESULTS: Across 7 sexual risk outcomes, and in middle and high
      school, LGBTQ-identified youths reported engaging in riskier behavior than did
      heterosexual-identified youths after we accounted for peer victimization. Risk
      differentials were present in middle and high school. The LGBTQ group was
      heterogeneous, with lesbian/gay- and bisexual-identified youths generally
      appearing most risky, and questioning-identified youths least risky. In the
      matched sample with lower average victimization rates, LGBTQ-identified youths
      perceived a greater risk of sexually transmitted infections despite not engaging
      in sexually risky behavior at significantly higher rates; in the matched sample
      with higher average victimization rates, all outcomes were significantly
      different. CONCLUSIONS: Demonstrated LGBTQ-heterosexual risk differentials in
      grades 7 through 8 suggest that interventions need to be implemented during
      middle school. These interventions should also be differentiated to address the
      unique risk patterns among LGBTQ subgroups. Finally, models of sexual risk
      disparities must expand beyond peer victimization.

PMID- 23948000
TI  - Denial of abortion because of provider gestational age limits in the United
      States.
AB  - OBJECTIVES: We examined the factors influencing delay in seeking abortion and the
      outcomes for women denied abortion care because of gestational age limits at
      abortion facilities. METHODS: We compared women who presented for abortion care
      who were under the facilities' gestational age limits and received an abortion (n
      = 452) with those who were just over the gestational age limits and were denied
      an abortion (n = 231) at 30 US facilities. We described reasons for delay in
      seeking services. We examined the determinants of obtaining an abortion elsewhere
      after being denied one because of facility gestational age limits. We then
      estimated the national incidence of being denied an abortion because of facility
      gestational age limits. RESULTS: Adolescents and women who did not recognize
      their pregnancies early were most likely to delay seeking care. The most common
      reason for delay was having to raise money for travel and procedure costs. We
      estimated that each year more than 4000 US women are denied an abortion because
      of facility gestational limits and must carry unwanted pregnancies to term.
      CONCLUSIONS: Many state laws restrict abortions based on gestational age, and new
      laws are lowering limits further. The incidence of being denied abortion will
      likely increase, disproportionately affecting young and poor women.

PMID- 23948001
TI  - Efficacy of initiating tobacco dependence treatment in inpatient psychiatry: a
      randomized controlled trial.
AB  - OBJECTIVES: We evaluated the efficacy of a motivational tobacco cessation
      treatment combined with nicotine replacement relative to usual care initiated in
      inpatient psychiatry. METHODS: We randomized participants (n = 224; 79%
      recruitment rate) recruited from a locked acute psychiatry unit with a 100%
      smoking ban to intervention or usual care. Prior to hospitalization, participants
      averaged 19 (SD = 12) cigarettes per day; only 16% intended to quit smoking in
      the next 30 days. Results. Verified smoking 7-day point prevalence abstinence was
      significantly higher for intervention than usual care at month 3 (13.9% vs 3.2%),
      6 (14.4% vs 6.5%), 12 (19.4% vs 10.9%), and 18 (20.0% vs 7.7%; odds ratio [OR] =
      3.15; 95% confidence interval [CI] = 1.22, 8.14; P = .018; retention > 80%).
      Psychiatric measures did not predict abstinence; measures of motivation and
      tobacco dependence did. The usual care group had a significantly greater
      likelihood than the intervention group of psychiatric rehospitalization (adjusted
      OR = 1.92; 95% CI = 1.06, 3.49). CONCLUSIONS: The findings support initiation of
      motivationally tailored tobacco cessation treatment during acute psychiatric
      hospitalization. Psychiatric severity did not moderate treatment efficacy, and
      cessation treatment appeared to decrease rehospitalization risk, perhaps by
      providing broader therapeutic benefit.

PMID- 23948002
TI  - School-based gay-affirmative interventions: first amendment and ethical concerns.
AB  - Public health professionals and educators have developed effective school-based
      interventions to reduce prejudice and stigma against lesbian, gay, bisexual, and
      transgender (LGBT) students. Such interventions can reduce the harm caused to
      sexual minority youths by stigma and can improve health outcomes. However,
      critics have warned that these interventions attempt to control speech and
      religious beliefs protected by the First Amendment. We review this critique and
      assess the legal and ethical arguments. We conclude that, both legally and
      ethically, there is great leeway for schools to implement LGBT-affirmative
      interventions. Still, we recommend that interventionists attend critics' concerns
      using principles of community-based participatory research (CBPR). Using CBPR
      approaches, interventionists can achieve better community acceptance and
      cooperation and more successful interventions. 

PMID- 23948003
TI  - To promote adoption of household health technologies, think beyond health.
AB  - Health risks from poor malaria control, unsafe water, and indoor air pollution
      are responsible for an important share of the global disease burden-and they can
      be addressed by efficacious household health technologies that have existed for
      decades. However, coverage rates of these products among populations at risk
      remain disappointingly low. We conducted a review of the medical and public
      health literatures and found that health considerations alone are rarely
      sufficient motivation for households to adopt and use these technologies. In
      light of these findings, we argue that health education and persuasion campaigns
      by themselves are unlikely to be adequate. Instead, health policymakers and
      professionals must understand what users value beyond health and possibly
      reengineer health technologies with these concerns in mind. 

PMID- 23948004
TI  - The impact of obesity on US mortality levels: the importance of age and cohort
      factors in population estimates.
AB  - OBJECTIVES: To estimate the percentage of excess death for US Black and White men
      and women associated with high body mass, we examined the combined effects of age
      variation in the obesity-mortality relationship and cohort variation in age
      specific obesity prevalence. METHODS: We examined 19 National Health Interview
      Survey waves linked to individual National Death Index mortality records, 1986
      2006, for age and cohort patterns in the population-level association between
      obesity and US adult mortality. RESULTS: The estimated percentage of adult deaths
      between 1986 and 2006 associated with overweight and obesity was 5.0% and 15.6%
      for Black and White men, and 26.8% and 21.7% for Black and White women,
      respectively. We found a substantially stronger association than previous
      research between obesity and mortality risk at older ages, and an increasing
      percentage of mortality attributable to obesity across birth cohorts.
      CONCLUSIONS: Previous research has likely underestimated obesity's impact on US
      mortality. Methods attentive to cohort variation in obesity prevalence and age
      variation in obesity's effect on mortality risk suggest that obesity
      significantly shapes US mortality levels, placing it at the forefront of concern
      for public health action.

PMID- 23948005
TI  - Grassroots movement building and preemption in the campaign for residential fire
      sprinklers.
AB  - Home fires account for 85% of fire deaths in the United States, the majority in 1
      or 2-family homes lacking fire sprinklers. Since 1978, however, a grassroots
      movement has successfully promoted more than 360 local ordinances mandating
      sprinklers in all new residential construction, including 1- and 2-family homes.
      The homebuilding industry has responded by seeking state preemption of local
      authority, a strategy previously used by other industries concerned about
      protecting their profits. From 2009 through 2011, 13 states adopted laws
      eliminating or limiting local authority over residential fire sprinklers. This
      study of the residential sprinkler movement adds to our understanding of
      grassroots public health movements and provides additional evidence that
      preemption can have a negative impact on public health and safety. 

PMID- 23948006
TI  - Capacity of US drug treatment facilities to provide evidence-based tobacco
      treatment.
AB  - Although people with drug problems consume a large proportion of cigarettes
      smoked in the United States, few drug treatment facilities offer tobacco
      treatment. Our analysis of 405 facilities showed that most had the skills but few
      had policies, leadership, or financial resources to provide evidence-based
      tobacco treatment. For-profits reported significantly fewer tobacco treatment
      resources than nonprofits. The Affordable Care and Mental Health Parity acts will
      improve treatment access for drug-dependent persons. To realize these acts' full
      promise, policymakers should ensure that clients have access to tobacco
      treatment. 

PMID- 23948007
TI  - The stigma of HIV.

PMID- 23948008
TI  - Marketing little cigars and cigarillos: advertising, price, and associations with
      neighborhood demographics.
AB  - OBJECTIVES: We have documented little cigar and cigarillo (LCC) availability,
      advertising, and price in the point-of-sale environment and examined associations
      with neighborhood demographics. METHODS: We used a multimodal real-time
      surveillance system to survey LCCs in 750 licensed tobacco retail outlets that
      sold tobacco products in Washington, DC. Using multivariate models, we examined
      the odds of LCC availability, the number of storefront exterior advertisements,
      and the price per cigarillo for Black & Mild packs in relation to neighborhood
      demographics. RESULTS: The odds of LCC availability and price per cigarillo
      decreased significantly in nearly a dose-response manner with each quartile
      increase in proportion of African Americans. Prices were also lower in some young
      adult neighborhoods. Having a higher proportion of African American and young
      adult residents was associated with more exterior LCC advertising. CONCLUSIONS:
      Higher availability of LCCs in African American communities and lower prices and
      greater outdoor advertising in minority and young adult neighborhoods may
      establish environmental triggers to smoke among groups susceptible to initiation,
      addiction, and long-term negative health consequences.

PMID- 23948009
TI  - Nonprescribed hormone use and self-performed surgeries: "do-it-yourself"
      transitions in transgender communities in Ontario, Canada.
AB  - OBJECTIVES: We examined the extent of nonprescribed hormone use and self
      performed surgeries among transgender or transsexual (trans) people in Ontario,
      Canada. METHODS: We present original survey research from the Trans PULSE
      Project. A total of 433 participants were recruited from 2009 to 2010 through
      respondent-driven sampling. We used a case series design to characterize those
      currently taking nonprescribed hormones and participants who had ever self
      performed sex-reassignment surgeries. RESULTS: An estimated 43.0% (95% confidence
      interval = 34.9, 51.5) of trans Ontarians were currently using hormones; of
      these, a quarter had ever obtained hormones from nonmedical sources (e.g., friend
      or relative, street or strangers, Internet pharmacy, herbals or supplements).
      Fourteen participants (6.4%; 95% confidence interval = 0.8, 9.0) reported
      currently taking nonprescribed hormones. Five indicated having performed or
      attempted surgical procedures on themselves (orchiectomy or mastectomy).
      CONCLUSIONS: Past negative experiences with providers, along with limited
      financial resources and a lack of access to transition-related services, may
      contribute to nonprescribed hormone use and self-performed surgeries. Promoting
      training initiatives for health care providers and jurisdictional support for
      more accessible services may help to address trans people's specific needs.

PMID- 23948010
TI  - Disparities in abortion rates: a public health approach.
AB  - Women of lower socioeconomic status and women of color in the United States have
      higher rates of abortion than women of higher socioeconomic status and White
      women. Opponents of abortion use these statistics to argue that abortion
      providers are exploiting women of color and low socioeconomic status, and thus,
      regulations are needed to protect women. This argument ignores the underlying
      causes of the disparities. As efforts to restrict abortion will have no effect on
      these underlying factors, and instead will only result in more women experiencing
      later abortions or having an unintended childbirth, they are likely to result in
      worsening health disparities. We provide a review of the causes of abortion
      disparities and argue for a multifaceted public health approach to address them. 

PMID- 23948011
TI  - Socioeconomic status and lung cancer: unraveling the contribution of genetic
      admixture.
AB  - OBJECTIVES: We examined the relationship between genetic ancestry, socioeconomic
      status (SES), and lung cancer among African Americans and Latinos. METHODS: We
      evaluated SES and genetic ancestry in a Northern California lung cancer case
      control study (1998-2003) of African Americans and Latinos. Lung cancer case and
      control participants were frequency matched on age, gender, and race/ethnicity.
      We assessed case-control differences in individual admixture proportions using
      the 2-sample t test and analysis of covariance. Logistic regression models
      examined associations among genetic ancestry, socioeconomic characteristics, and
      lung cancer. RESULTS: Decreased Amerindian ancestry was associated with higher
      education among Latino control participants and greater African ancestry was
      associated with decreased education among African lung cancer case participants.
      Education was associated with lung cancer among both Latinos and African
      Americans, independent of smoking, ancestry, age, and gender. Genetic ancestry
      was not associated with lung cancer among African Americans. CONCLUSIONS:
      Findings suggest that socioeconomic factors may have a greater impact than
      genetic ancestry on lung cancer among African Americans. The genetic
      heterogeneity and recent dynamic migration and acculturation of Latinos
      complicate recruitment; thus, epidemiological analyses and findings should be
      interpreted cautiously.

PMID- 23948012
TI  - The impact of emotional, physical, and sexual abuse on contraceptive method
      selection and discontinuation.
AB  - OBJECTIVES: We evaluated the impact of exposure to emotional, physical, or sexual
      abuse on contraceptive method selection and discontinuation. METHODS: We
      performed a secondary analysis of 7170 women enrolled in the Contraceptive CHOICE
      Project in St. Louis, Missouri, a prospective cohort study in which 9256 women
      were provided their preferred method of contraception at no cost from 2007 to
      2011. We defined contraceptive discontinuation as device removal or nonuse for at
      least 4 weeks within the first 12 months after initiation. RESULTS: One third of
      women experienced some abuse in their lifetimes. Women with an abuse history were
      as likely as those without to select a long-acting reversible contraceptive
      method and more likely to choose a contraceptive injection, the patch, or the
      ring. When we compared women who were abused to those who were not, rates of
      discontinuation at 12 months were higher among women who selected long-acting
      reversible contraception (17% vs 14%; P = .04) and significantly higher among
      women who selected non-long-acting methods (56% vs 47%; P < .001). Type of abuse
      did not alter the association between abuse and contraceptive continuation.
      CONCLUSIONS: Previous experiences of abuse are associated with both contraceptive
      method selection and continuation.

PMID- 23948013
TI  - Only your calamity: the beginnings of activism by and for people with AIDS.
AB  - The invention of AIDS activism came soon after the AIDS epidemic emerged in gay
      communities in the United States in the early 1980s. AIDS activism by and for
      people with AIDS, distinct from gay activism responding to the threat of AIDS on
      the behalf of the whole community, started as a way of resisting the phenomenon
      of social death. Social death, in which people are considered "as good as dead"
      and denied roles in community life, posed a unique threat to people with AIDS. An
      organized political response to AIDS began among gay men with AIDS in San
      Francisco, California, and New York, New York, formalized in a foundational
      document later called the Denver Principles. The ideas and language of these
      first people with AIDS influenced later AIDS activism movements. They also help
      to illustrate the importance of considering an epidemic from the point of view of
      people with the disease. 

PMID- 23948014
TI  - An assessment of the performance of self-reported vaccination status for
      hepatitis B, National Health and Nutrition Examination Survey 1999-2008.
AB  - OBJECTIVES: We sought to assess the performance of self-reported vaccination with
      hepatitis B vaccine (HepB) compared with serological status for hepatitis B
      markers in the general US civilian population. METHODS: Using 1999 through 2008
      National Health and Nutrition Examination Survey data, we calculated 3 measures
      of agreement between self-reported HepB vaccination status and serological
      status: percent concordance, and positive (PPV) and negative predictive values
      (NPV) of self-report. Logistic regression was used to identify factors associated
      with agreement between self-report and serological status. RESULTS: Overall
      agreement was 83% (95% CI = 82.3, 83.7), NPV of self-report was high (0.95; 95%
      CI = 0.93, 0.95) and PPV was low (0.53; 95% CI = 0.51, 0.54). Birth year relative
      to the 1991 recommendation for universal infant HepB vaccination had a strong
      association with agreement, however, the association was positive for those who
      reported receiving at least 3 doses and negative for those who reported receiving
      no doses. CONCLUSIONS: Although the low PPV in our study could be attributable in
      part to waning of vaccine-induced anti-HBs over time, national adult HepB
      vaccination coverage may be lower than previously estimated because national
      estimates usually depend on self-report of vaccine receipt.

PMID- 23948015
TI  - A situated practice of ethics for participatory visual and digital methods in
      public health research and practice: a focus on digital storytelling.
AB  - This article explores ethical considerations related to participatory visual and
      digital methods for public health research and practice, through the lens of an
      approach known as "digital storytelling." We begin by briefly describing the
      digital storytelling process and its applications to public health research and
      practice. Next, we explore 6 common challenges: fuzzy boundaries, recruitment and
      consent to participate, power of shaping, representation and harm,
      confidentiality, and release of materials. We discuss their complexities and
      offer some considerations for ethical practice. We hope this article serves as a
      catalyst for expanded dialogue about the need for high standards of integrity and
      a situated practice of ethics wherein researchers and practitioners reflexively
      consider ethical decision-making as part of the ongoing work of public health. 

PMID- 23948016
TI  - Health and safety of child care centers: an analysis of licensing specialists'
      reports of routine, unannounced inspections.
AB  - OBJECTIVES: We assessed the prevalence of regulatory noncompliance of licensed
      child care centers and identified factors associated with improved compliance.
      METHODS: We analyzed 676 routine, unannounced reports of child care centers
      collected by the Connecticut Department of Public Health licensing specialists
      over a 2-year time period, included characteristics of centers, and created
      categories of regulations. RESULTS: The sample included 41% of licensed child
      care centers. Of the 13 categories of regulations in the analyses, 7 categories
      (outdoor safety, indoor safety, indoor health, child and staff documentation,
      emergency preparedness, infant-toddler indoor health, and infant-toddler indoor
      safety) had regulations with center noncompliance greater than 10%. Playground
      hazard-free was the regulation with the highest frequency (48.4%) of
      noncompliance. Compliance with the regulation for 20 hours of continuing
      education per year for child care providers was the characteristic most
      frequently associated with regulations compliance. CONCLUSIONS: Efforts to
      support continuing education of child care providers are essential to improve and
      sustain healthy and safe early-care and education programs. Analyses of state
      child care licensing inspection reports provide valuable data and findings for
      strategic planning efforts.

PMID- 23948017
TI  - Lessons learned from use of social network strategy in HIV testing programs
      targeting African American men who have sex with men.
AB  - OBJECTIVES: We report lessons derived from implementation of the Social Network
      Strategy (SNS) into existing HIV counseling, testing, and referral services
      targeting 18- to 64-year-old Black gay, bisexual, and other men who have sex with
      men (MSM). METHODS: The SNS procedures used in this study were adapted from a
      Centers for Disease Control and Prevention-funded, 2-year demonstration project
      involving 9 community-based organizations (CBOs) in 7 cities. Under the SNS, HIV
      positive and HIV-negative men at high risk for HIV (recruiters) were enlisted to
      identify and recruit persons from their social, sexual, or drug-using networks
      (network associates) for HIV testing. Sites maintained records of modified study
      protocols for ascertaining lessons learned. The study was conducted between April
      2008 and May 2010 at CBOs in Washington, DC, and New York, New York, and at a
      health department in Baltimore, Maryland. RESULTS: Several common lessons
      regarding development of the plan, staffing, training, and use of incentives were
      identified across the sites. Collectively, these lessons indicate use of SNS is
      resource-intensive, requiring a detailed plan, dedicated staff, and continual
      input from clients and staff for successful implementation. CONCLUSIONS: SNS may
      provide a strategy for identifying and targeting clusters of high-risk Black MSM
      for HIV testing. Given the resources needed to implement the strategy, additional
      studies using an experimental design are needed to determine the cost
      effectiveness of SNS compared with other testing strategies.

PMID- 23948018
TI  - A population-based study of cardiovascular disease risk in sexual-minority women.
AB  - OBJECTIVES: We sought to determine if sexual-minority women were at greater risk
      for cardiovascular disease (CVD) than their heterosexual counterparts. METHODS:
      We aggregated data from the 2001-2008 National Health and Nutrition Examination
      Surveys to examine differences in CVD risk between heterosexual and sexual
      minority women by using the Framingham General CVD Risk Score to calculate a
      ratio of vascular and chronological age. We also examined differences in the
      prevalence of various CVD risk factors. RESULTS: Sexual-minority women were more
      likely to be current or former smokers, to report a history of drug use, to
      report risky drinking, and to report a family history of CVD. On average, sexual
      minority women were 13.9% (95% confidence interval [CI] = 8.5%, 19.3%) older in
      vascular terms than their chronological age, which was 5.7% (95% CI = 1.5%, 9.8%)
      greater than that of their heterosexual counterparts. Family history of CVD and
      history of drug use were unrelated to increased CVD risk, and this risk was not
      fully explained by either risky drinking or smoking. CONCLUSIONS: Sexual-minority
      women are at increased risk for CVD compared with heterosexual women.

PMID- 23948019
TI  - Sexual orientation-related differences in tobacco use and secondhand smoke
      exposure among US adults aged 20 to 59 years: 2003-2010 National Health and
      Nutrition Examination Surveys.
AB  - OBJECTIVES: We investigated sexual orientation-related differences in tobacco use
      and secondhand smoke (SHS) exposure in a nationally representative sample of US
      adults. METHODS: The 2003-2010 National Health and Nutrition Examination Surveys
      assessed 11 744 individuals aged 20 to 59 years for sexual orientation, tobacco
      use, and SHS exposure (cotinine levels >= 0.05 ng/mL in a nonsmoker). We used
      multivariate methods to compare tobacco use prevalence and SHS exposure among gay
      or lesbian (n = 180), bisexual (n = 273), homosexually experienced (n = 388), and
      exclusively heterosexual (n = 10 903) individuals, with adjustment for
      demographic confounding. RESULTS: Lesbian and bisexual women evidenced higher
      rates of tobacco use than heterosexual women. Among nonsmokers, SHS exposure was
      more prevalent among lesbian and homosexually experienced women than among
      heterosexual women. Nonsmoking lesbians reported greater workplace exposure and
      bisexual women greater household exposure than heterosexual women did. Identical
      comparisons among men were not significant except for lower workplace exposure
      among nonsmoking gay men than among heterosexual men. CONCLUSIONS: Nonsmoking
      sexual-minority women are more likely to be exposed to SHS than nonsmoking
      heterosexual women. Public health efforts to reduce SHS exposure in this
      vulnerable population are needed.

PMID- 23948020
TI  - Comprehensive evaluation of a patient with Kawasaki disease and giant coronary
      aneurysms with cardiac magnetic resonance.
AB  - In patients with Kawasaki disease (KD) and coronary artery aneurysms (CAAs),
      serial evaluation with multiple imaging modalities is recommended to guide risk
      stratification and management. We present the case of a 7-year-old boy with a
      history of KD and multiple giant CAAs who developed thrombosis in one of the
      aneurysms. We illustrate how cardiac magnetic resonance is unique in allowing a
      comprehensive assessment in patients with severe KD and how it may affect their
      management. 

PMID- 23948021
TI  - Linezolid-induced hyperlactatemia in a burn patient.

PMID- 23948022
TI  - [Diagnostic difficulty for an acute hydrocephalus].
AB  - Tuberculosis disease, in its extra pulmonary form, remains a difficult diagnosis
      because of its atypical symptoms and evolution. We have observed a case of acute
      tuberculosis neuromeningitis, without being able to make a definite diagnosis
      prior to the patient's death because of the negativity of the initial
      bacteriological samples. We started the most probable appropriate treatment but
      in vain. This case allows us to challenge diagnostic methods and resulting
      treatments in emergency cases where tuberculosis is suspected. Moreover, it seems
      essential to do everything possible to find the bacterium when confronted with a
      patient with risk factors and clinical and radiological symptoms compatible with
      tubercular disease, before the disease becomes acute. 

PMID- 23948023
TI  - [Influence of pressure- and volume-controlled ventilation on pulse pressure
      variations: randomized study].
AB  - OBJECTIVE: Pulse pressure variation (DeltaPP) has been demonstrated to be an
      accurate dynamic parameter to predict fluid responsiveness. However, the impact
      of different ventilator modes on this parameter is unknown. We compared DeltaPP
      values calculated alternatively during pressure- and volume-controlled
      ventilation. STUDY DESIGN: Double-blind randomized study, cross-over design.
      PATIENTS: Patients in intensive care unit after a cardiac surgery. METHOD:
      Patients were ventilated alternatively in both ventilator modes (according to the
      randomization): volume-controlled ventilation (VVC) and pressure-controlled
      ventilation (VPC). Other parameters of ventilation were identical. DeltaPP values
      were calculated for each patient in both ventilator modes. RESULTS: Among the 26
      patients analyzed, mean DeltaPP value was de 14.0+/-7.3% in VVC and 11.8+/-6.2%
      in VPC (P<0,0001). On Bland-Altman representation, mean bias was +2.2+/-2.3% and
      inferior and superior limits of agreement were respectively -2.3 and 6.7%.
      Arterial blood pressure and central venous pressure were not modified.
      CONCLUSION: DeltaPP values obtained with both ventilator modes were not
      interchangeable. On average, DeltaPP decreases by more than two points in the
      passage VVC to VPC for a given patient, all others things being equal.

PMID- 23948024
TI  - Ultrasound-guided regional anesthesia.

PMID- 23948025
TI  - [Bacterial parotitis in an immunocompromised patient in adult ICU].
AB  - Bacterial parotitis is a common childhood disease with a favorable outcome.
      Staphylococcus aureus is the most frequently involved pathogen. Clinical
      presentation in adult patients can be misleading, Onset occurs in patients with
      multiple comorbidities, making diagnosis difficult--particularly in ICU.
      Different pathogens are found in adults with worse outcomes observed. We report
      here the case of a critically ill patient and discuss diagnosis and management of
      bacterial parotitis.

PMID- 23948026
TI  - [About technical difficulties due to oral premedication by gastric endoscopy].

PMID- 23948027
TI  - [Predictive factors of organ failure in patients admitted in intensive care unit
      for acute gastrointestinal bleeding].
AB  - INTRODUCTION: Gastrointestinal hemorrhage is an emergency requiring usually an
      admission in intensive care unit (ICU), which may prove abusive secondarily. The
      aim of this study was to identify predictive risk factors of organ failure in
      patients admitted for GH in our ICU. DESIGN: Retrospective and observational
      METHODS AND MEASUREMENTS: Between January 2008 and December 2011, all patients
      admitted in our ICU for gastrointestinal hemorrhage were consecutively included.
      The primary endpoint was the occurrence of at least an organ failure. We realized
      an univariate analysis then a backward regression to identify independent risk
      factors associated with the occurrence of at least one organ failure during the
      ICU hospitalization. RESULTS: During this period study, 441 consecutive patients
      with a mean age of 67+/-15years were included. The median ICU length of stay was
      of 4 (3-7) days and 116 (26% [IC95%: 22-30]) patients presented at least one
      organ failure. The multivariate analysis identified predictive risk factors of
      organ failure: history of cirrhosis (OR=3.5 [IC95%: 1.9-6.7], P<0.001) and an
      increase in troponin at the admission above the 99th percentile (OR=3.1 [IC95%:
      1.8-5.5], P<0.001). CONCLUSION: Our results confirmed that a large proportion of
      patients admitted in ICU for the primary diagnosis of gastrointestinal hemorrhage
      developed any organ failure. The history of cirrhosis and the systemic
      consequences of the hemorrhagic syndrome as myocardial damage represents
      important risk factors of morbidity and mortality and thus should be considered
      during the management.

PMID- 23948028
TI  - [Explorers].

PMID- 23948029
TI  - [Multiple organ failure complicating a severe acute necrotising pancreatitis
      secondary of a severe hypertriglyceridemia: a case report].
AB  - We report the case of a 42-year-old man admitted for a multi-organ failure with a
      coma, a hemodynamic instability, a respiratory distress syndrome, an acute renal
      failure and a thrombocytopenia. The blood samples highlighted a milky serum and
      allowed to diagnose an acute pancreatitis associated with a major dyslipidemia:
      hypertriglyceridemia 11,800 mg/dL and hypercholesterolemia 1195 mg/dL. The CT
      scans do not reveal any cerebral abnormalities but highlighted pancreatic lesions
      without biliary obstruction. A multi-organ failure complicating a severe acute
      pancreatitis secondary of a major hypertriglyceridemia was mentioned. Despite the
      absence of clear guidelines, a session of plasma exchange was started in
      emergency. Symptomatic treatment with protective ventilation, vasopressors,
      continuous heparin and insulin was continued. The clinical and biological course
      was good in parallel of the normalization of lipid abnormalities. The patient was
      discharged at day 17 with a lipid-lowering therapy. We discuss the various
      treatments available for the management of acute pancreatitis complicating a
      severe hypertriglyceridemia and their actual relevance in the absence of clear
      recommendations.

PMID- 23948030
TI  - [Predictors indices of fluid responsiveness: readily dynamics but not without
      limits!].

PMID- 23948031
TI  - The cosmetic allergy conundrum: inference of an immunoregulatory response to
      cosmetic allergens.
AB  - The ability to be sensitized to experimental contact allergens declines
      significantly with increasing age, from as early as age 40 years. In contrast,
      the rate of contact allergy to chemical allergens (haptens) in cosmetic products
      significantly increases with age. This has been explained previously on the basis
      of greater cumulative exposure in the older age groups. However, outbreaks of
      contact allergy to preservatives in cosmetic products recorded soon after their
      introduction to the market have also shown a significantly higher rate among
      older adult age groups. This association with increasing age cannot be readily
      explained by exposure history or pattern, and is not compatible with a
      sensitizing/stimulatory reaction that degrades with age as the sole immune
      response. From this, the existence of a second, tolerizing/regulatory arm to the
      immune response to cutaneous haptens that possibly becomes less effective with
      age at a higher rate than the sensitizing/stimulatory arm can be inferred. This
      reinforces the view that current clinical and experimental observations of
      allergic contact dermatitis are best explained by an immune system with the
      functional ability to produce both sensitizing/stimulatory and
      tolerizing/regulatory responses.

PMID- 23948032
TI  - Hand eczema and health-related quality of life; a comparison of EQ-5D and the
      Dermatology Life Quality Index (DLQI) in relation to the Hand Eczema Extent Score
      (HEES).
AB  - BACKGROUND: Health-related quality of life (HRQoL) is associated with the extent
      and severity of hand eczema. We still lack a consensus about which HRQoL
      instrument to use as the standard, and how to measure the extent and severity of
      hand eczema. OBJECTIVES: To compare the Dermatology Life Quality Index (DLQI)
      with EQ-5D (a standardized instrument for use as a measure of health outcome),
      and to evaluate how the Hand Eczema Extent Score (HEES) relates to these
      instruments. METHODS: Ninety-three patients (61 females) were included. The HEES
      was recorded by a dermatologist, and the DLQI and EQ-5D by the patients. The
      results were analysed with factor analysis and non-parametric statistics.
      RESULTS: The DLQI and EQ-5D showed decreased HRQoL. Using factor analysis, we
      could not establish an association between the DLQI and EQ-5D. There were,
      however, correlations between the DLQI and the HEES (0.31), the EQindex and the
      HEES (-0.32), the DLQI and the EQVAS (-0.62), and the DLQI and the EQindex (
      0.67) (the EQVAS and the EQindex are calculated from EQ-5D). CONCLUSIONS: We
      could not link factors in the DLQI to EQ-5D, which has previously been done for
      SF-36 (Short Form 36). On the basis of this, we cannot recommend EQ-5D over SF-36
      for hand eczema studies. The DLQI correlates with the EQVAS and the EQindex, and
      can probably be used as an approximation for EQ-5D. Our findings with the HEES
      are interesting, as it can be used by patients.

PMID- 23948033
TI  - Occupational allergic contact dermatitis diagnosed by a systematic stepwise
      exposure assessment of allergens in the work environment.
AB  - BACKGROUND: Information on the presence of contact allergens and irritants is
      crucial for the diagnosis of occupational contact dermatitis. Ingredient lists
      and Material Safety DataSheets (MSDSs) may be incomplete. OBJECTIVES: To evaluate
      the workability of a systematic exposure assessment in consecutive patients with
      suspected occupational contact dermatitis, and to study how it could potentially
      aid correct diagnostic classification. METHODS: A tool for systematic stepwise
      assessment of exposures in the work environment was developed, consisting of six
      steps spanning medical history and workplace visits. The programme included 228
      consecutive patients diagnosed with occupational contact dermatitis; all patients
      underwent a clinical examination, the stepwise exposure assessment, and extensive
      patch and prick testing. RESULTS: Of the participants, 48.2% were classified as
      having occupational allergic contact dermatitis. The diagnosis was made at the
      stepwise exposure assessment for 50.0% of patients at Step 1 (medical history)
      and for 34.5% at Step 2 (ingredient labelling/MSDS). We found 132 different
      occupational allergens of relevance to the patients' eczema, of these, 78.0% were
      allergens not included in the European baseline series. CONCLUSIONS: Systematic
      stepwise exposure assessment provides information that results in the
      identification of occupational allergies caused by allergens not included in the
      European baseline series in a substantial number of patients.

PMID- 23948034
TI  - A positive cobalt spot test falsely indicating an occupational allergic contact
      dermatitis caused by cobalt.
AB  - BACKGROUND: For investigation of chemical exposure in allergic individuals, spot
      tests are invaluable. A reagent may react with a specific compound to give a
      specific typical colour, and thus indicate the presence of the specific
      substance. Spot tests can give both false-negative and false-positive reactions.
      To confirm the presence of the substance and quantify it, more sophisticated
      methods are required. On the basis of a positive cobalt spot test result, a woman
      was initially diagnosed with an occupational allergic contact dermatitis caused
      by cobalt. OBJECTIVES: To investigate cobalt release from three different metal
      weaves to which our patient was occupationally exposed. METHODS: The cobalt gel
      test and atomic absorption spectroscopy (AAS) were used to investigate the metal
      weaves. Two types of extract based on artificial sweat and nitric acid,
      respectively, were investigated with AAS. RESULTS: No cobalt release was
      demonstrated with AAS. CONCLUSIONS: When a diagnosis of allergic contact
      dermatitis caused by a sensitizer based on a positive spot test result will have
      far-reaching consequences, such as change of work, retraining, and claim on and
      payment of worker's compensation, conformational analysis must be performed.

PMID- 23948035
TI  - Chemical burns caused by trifluoroacetic acid.
AB  - BACKGROUND: Trifluoroacetic acid is a very strong carboxylic acid. The acid has
      been suspected to have similar toxic effects as hydrofluoric acid on skin
      contact. Hydrofluoric acid is highly toxic, owing to skin penetration by fluoride
      ions. A spill of hydrofluoric acid on the skin may be fatal. As trifluoroacetic
      acid contains fluorine, patients with chemical burns caused by trifluoroacetic
      acid have been given particular attention when treated in the hospital.
      OBJECTIVES: To gather the known cases of trifluoroacetic acid burns from our
      department to give an overview of how they were exposed, the clinical
      presentation, and treatment. METHODS: Five patients with chemical skin burns
      caused by trifluoroacetic acid were reviewed with regard to the extent of the
      burn, treatment, blood samples taken, and systemic effects. RESULTS: The chemical
      burns reported were limited (<1% of the total body surface). The burns healed as
      expected for chemical burns caused by acids. None of the patients showed any
      symptoms or signs that are typical for hydrofluoric acid burns. CONCLUSION:
      Localized chemical burns caused by trifluoroacetic acid should be regarded as
      being similar to burns from other acids, with the exception of hydrofluoric acid.
      To our knowledge, there are no indications that trifluoroacetic acid causes the
      same toxic effects as hydrofluoric acid.

PMID- 23948036
TI  - Contact dermatitis caused by lovage (Levisticum officinalis) essential oil.

PMID- 23948037
TI  - Allergic reaction to condom catheter for bladder incontinence.

PMID- 23948038
TI  - A case of anaphylaxis caused by polyethylene glycol analogues.

PMID- 23948039
TI  - Allergic contact dermatitis caused by Glycofilm(r) 1.5P contained in an anti
      wrinkle cream.

PMID- 23948040
TI  - Co-sensitization to ascaridole and tea tree oil.

PMID- 23948041
TI  - Contact dermatitis caused by bromide compounds.

PMID- 23948042
TI  - Ethnic differences in the wellness of elderly persons.
AB  - The purpose of this qualitative research study was to determine the health
      behaviors, attitudes and beliefs of well-elderly persons from Black, German,
      Hispanic, Vietnamese and White rural and city ethnic groups. Findings from the
      ethnographies and life histories of the twenty-eight informants revealed
      similarities and differences in health-related themes. These compared favorably
      with wellness dimensions of self-responsibility, social interaction,
      spirituality, exercise and nutrition, environmental factors, stress management
      and balance of work and leisure. Occupational therapists who provide health
      promotion and disease prevention services to minority elders can be more
      effective if they become sensitive to cultural as well as individual differences
      in treatment planing and implementation. 

PMID- 23948043
TI  - Attitudinal changes toward exercise in mexican american women.
AB  - BACKGROUND: This experimental study was designed to examine the attitude changes
      and exercise adherence of a group of sedentary minority women. METHOD: Fifty
      sedentary Mexican American women participated in a 9-month, biweekly education
      and exercise program that was preceded by a 6-month program initiation composed
      of weekly interactions to facilitate trust between participants and researchers.
      RESULTS: Compared to Mexican American and Caucasian control groups, the
      experimental participants displayed significant changes in scores on the Exercise
      Benefits and Barriers Scales (EBBS) at three, six, and nine months. Adherence to
      the physical activity program was 84%. At pre-test, the Mexican American
      participants and controls displayed significantly lower EBBS scores than the
      Caucasian controls. CONCLUSIONS: The results of this study are examined in light
      of existing reports on the facilitation of attitudes toward exercise, exercise
      adherence and health promotion particularly in regard to understanding the
      barriers to physical activity for minorities. The findings of this study are
      particularly important given the paucity of research about health promotion for
      individuals who belong to minority groups.

PMID- 23948044
TI  - Adolescent social action program: involvement of occupational therapy students in
      an innovative health promotion program.
AB  - Health promotion is a promising but underutilized area of occupational therapy
      practice. In order for occupational therapy practitioners to increase their
      involvement in wellness and prevention programs, it is necessary for students to
      gain relevant fieldwork experience. This article describes the involvement of
      occupational therapy undergraduate students at the University of New Mexico in a
      health promotion program targeting youth. The program is based on an empowerment
      model emphasizing active learning methods and involvement of participants in all
      phases of the program. Specific examples of occupational therapy student projects
      are identified, and implications for future practice are discussed. 

PMID- 23948045
TI  - Factors Which Motivate the Certified Occupational Therapy Assistant (COTA) to
      Become a Registered Occupational Therapist (OTR).
AB  - Objective. This survey study was conducted to describe the motivational factors
      which commonly inspire the certified occupational therapy assistant (COTA) to
      seek advanced education to become a registered occupational therapist (OTR).
      Methods. A triangulated literature review was employed to articulate the
      knowledge base surrounding factors motivating adult learners and to identify a
      theoretical framework for developing a survey tool. A questionnaire was developed
      based on a literature review, piloted, refined, and administered to 267 COTAs
      enrolled in four education programs designed to ladder them to OTR credentialing.
      A descriptive analysis of emerging common themes was conducted. Results. The
      results confirmed the findings in the literature. The two major factors
      motivating COTAs to pursue OTR credentials are professional advancement and
      cognitive interest. Variations, however, were identified relating to other
      motivating factors among those COTAs surveyed. These factors are in order of
      educational preparation, communication improvement, social contact, family
      togetherness, and social stimulation. Conclusions. Cognitive interest and
      professional advancement were found to be the factors which motivate COTAs to
      seek OTR credentials. Issues of professional identity and respect from others
      emerged as related themes, as well as career mobility. As managed care affects
      market shifts and the demand for OT personnel, further research is necessary to
      help educational programs tool their programs accordingly. 

PMID- 23948046
TI  - Critical pathways: occupational therapists' role in development and utilization.
AB  - Managed care is mandating that healthcare facilities implement cost containment
      measures. Critical pathways are one popular tool used to meet this demand. The
      purpose of this study was to explore current involvement of occupational
      therapists (OTRs) in the use and creation of critical pathways. Results of a
      national survey showed 70.5% of the respondents reported they are not currently
      using critical pathways. A majority of OTRs are not and have not taken an active
      role in critical pathway development. Furthermore, the majority indicated having
      no knowledge of future critical pathway implementation in their facilities.
      Information gathered from those OTRs reporting critical path use included most
      common diagnoses using the paths and percentages of OTRs utilizing critical paths
      in specific occupational therapy areas. The conclusions drawn by the researchers
      indicated the need for OTRs to become more involved in the development and
      utilization of this multi-disciplinary approach to treatment. For OTRs to
      maintain and enhance their positions within the allied health profession,
      proactive involvement with these managed care driven quality assurance methods is
      essential. 

PMID- 23948047
TI  - Occupational therapists as case managers.
AB  - Occupational therapists in today's health care environment are challenged to take
      on new roles such as case management. In assuming these roles occupational
      therapists need an understanding of the basic competencies to perform the job. To
      determine these competencies, the author, an occupational therapist, compares the
      basic competencies necessary to practice as a certified case manager and as a
      certified occupational therapist. As a participant/observer of case management
      she considers these competencies in clinical practice. From that experience she
      identifies strengths and suggestions for further occupational therapy educational
      development. 

PMID- 23948048
TI  - What is community-based rehabilitation: an implication of the roles of community
      occupational therapists in Hong Kong.
AB  - With a world-wide trend in de-institutionalization and community care, community
      based rehabilitation is considered to be more cost-effective in covering the
      needs of persons with chronic illness and their families. Since the inauguration
      of Hospital Authority in 1990, the emphasis on creating a 'seamless' health care
      system had further reinforced the significance of the development of community
      based rehabilitation services in Hong Kong. This also implied the demand for
      community occupational therapy services as well as the emerging roles of the
      community occupational therapists. In 1994, Community Rehabilitation Network
      (CRN) was established as a pioneer service operated on the basis of community
      based rehabilitation and with the development of community occupational therapy
      services. This paper will first review the demand and importance of community
      based rehabilitation services, especially for persons with chronic illness in
      Hong Kong. With an understanding of this background, this paper then describes
      the goals and scopes of service as well as future development of community
      occupational therapists, with reference to its specific role in Community
      Rehabilitation Network. 

PMID- 23948049
TI  - Investigating the association between oral hygiene and head and neck cancer.
AB  - OBJECTIVES: This analysis examined the association between oral hygiene and head
      and neck cancer (HNC) and whether this association differed by the consumption of
      alcohol, betel quid, or cigarette and by the genetic polymorphisms of
      inflammation-related genes. MATERIALS AND METHODS: Interviews regarding dental
      care and oral health were conducted with 317 HNC cases and 296 controls.
      Genotyping was performed for 6 single nucleotide polymorphisms in IL6, IL10 and
      PTGS2. RESULTS: A positive association was observed between HNC and no regular
      dental visits (odds ratio (OR)=2.86, 95% confidence interval (CI): 1.47-5.57),
      brushing teeth <2times/day (OR=1.51, 95% CI: 1.02-2.23), frequent gum bleeding
      (OR=3.15, 95% CI: 1.36-7.28), and loss of >20 teeth (OR=2.31, 95% CI: 1.05-5.07).
      Analysis with dental care score (range: 0-4, 4=worst dental care), which combined
      regular dental visits, toothbrushing, and use of dental floss and mouthwash,
      showed a positive trend with HNC risk, particularly among alcohol drinkers and
      cigarette smokers. Multifactor dimensionality reduction analysis divided the
      study subjects into high- and low-risk group based on combinations of dental care
      score and IL6 rs1800796 genotypes. Compared to the low-risk group, the high-risk
      group had an OR of HNC=2.16 (95% CI: 1.44-3.25). CONCLUSIONS: This study observed
      a positive association between poor oral hygiene and HNC, which appeared to
      differ by alcohol or cigarette consumption and the genotypes of IL6 rs1800796.
      Further investigations are needed to determine whether poor oral hygiene is a
      cause for HNC or a surrogatemarker of an unhealthy lifestyle that increases the
      risk of HNC.

PMID- 23948050
TI  - Sulfide emissions from different areas of a municipal solid waste landfill in
      China.
AB  - Degradation of municipal solid waste in landfills generates sulfide compounds,
      which are considered one of the main sources of odor emissions. Field sampling
      was conducted at surfaces of operating, inoperative, and soil-covered areas of a
      landfill site in northern China to characterize the sulfide compounds. The
      results showed that dimethyl disulfide dominated the sulfide compounds,
      accounting for up to 73.6% of the total detected sulfide. With the biggest odor
      concentration of 365, diethyl sulfide was the most significant sulfide compound.
      The estimated sulfide emission rates at surfaces of operating and soil-covered
      areas were similar, and the emission rate of dimethyl disulfide at Surface of
      Operating Area was up to 345.9 MUg/m(3) h. Dimethyl disulfide could be released
      from the fresh waste, and its normalized concentration at 0.2 m beneath operating
      surface was 10.4 times that at 0.4 m.

PMID- 23948052
TI  - Improvement actions in waste management systems at the provincial scale based on
      a life cycle assessment evaluation.
AB  - This paper reports some of the findings of the 'GERLA' project: GEstione Rifiuti
      in Lombardia - Analisi del ciclo di vita (Waste management in Lombardia - Life
      cycle assessment). The project was devoted to support Lombardia Region in the
      drafting of the new waste management plan by applying a life cycle thinking
      perspective. The present paper mainly focuses on four Provinces in the Region,
      which were selected based on their peculiarities. Life cycle assessment (LCA) was
      adopted as the methodology to assess the current performance of the integrated
      waste management systems, to discuss strengths and weaknesses of each of them and
      to design their perspective evolution as of year 2020. Results show that despite
      a usual business approach that is beneficial to all the provinces, the
      introduction of technological and management improvements to the system provides
      in general additional energy and environmental benefits for all four provinces.
      The same improvements can be easily extended to the whole Region, leading to
      increased environmental benefits from the waste management sector, in line with
      the targets set by the European Union for 2020. 

PMID- 23948051
TI  - Porous materials produced from incineration ash using thermal plasma technology.
AB  - This study presents a novel thermal plasma melting technique for neutralizing and
      recycling municipal solid waste incinerator (MSWI) ash residues. MSWI ash
      residues were converted into water-quenched vitrified slag using plasma
      vitrification, which is environmentally benign. Slag is adopted as a raw material
      in producing porous materials for architectural and decorative applications,
      eliminating the problem of its disposal. Porous materials are produced using
      water-quenched vitrified slag with Portland cement and foaming agent. The true
      density, bulk density, porosity and water absorption ratio of the foamed
      specimens are studied here by varying the size of the slag particles, the water
      to-solid ratio, and the ratio of the weights of the core materials, including the
      water-quenched vitrified slag and cement. The thermal conductivity and flexural
      strength of porous panels are also determined. The experimental results show the
      bulk density and the porosity of the porous materials are 0.9-1.2 g cm(-3) and 50
      60%, respectively, and the pore structure has a closed form. The thermal
      conductivity of the porous material is 0.1946 W m(-1) K(-1). Therefore, the slag
      composite materials are lightweight and thermal insulators having considerable
      potential for building applications.

PMID- 23948053
TI  - Investigation on characteristics of leachate and concentrated leachate in three
      landfill leachate treatment plants.
AB  - Concentrated leachate from membrane treatment processes is a potential pollution
      source for the surroundings. In this study, with comparison of the landfill
      leachate, chemical and microbial characteristics of concentrated leachate
      including biodegradability, amount of nitrogenous compounds and heavy metals,
      dissolved organic matter composition, and microbial community were investigated
      in three landfill leachate treatment plants. The results showed that hydrophilic
      (HyI) fraction was the major dissolved organic carbon in the landfill leachates,
      accounting for 54.6-60.7%, while humic substances including humic acid (HA) and
      fulvic acid (FA) were relatively higher in the concentrated leachates, ranging
      from 61.7% to 69.2%. Conjugated nitrogen existed mainly in FA and HyI in the
      concentrated leachates. The analysis of excitation emission matrix fluorescence
      spectroscopy, specific ultraviolet absorbance at 254nm (SUVA254) and GC/MS showed
      that aromatic compounds, long-chain hydrocarbons and halohydrocarbons were
      abundant in the concentrated leachates. During landfill leachate treatment
      processes, Cl(-), SO4(2-) and heavy metals were commonly accumulated in the
      concentrated leachates. NO3(-)N and/or NH4(+)N were the major nitrogenous
      compounds in the concentrated leachates. All the leachates from three landfill
      sites contained toluene in the range of 44.5-728.4MUgL(-1). Ethylbenzene,
      chlorobenzene, and the phthalic acid esters including dibutyl phthalate, dimethyl
      phthalate and di-n-octyl phthalate were also detected in the concentrated
      leachates. Higher microbial diversity was observed in the concentrated leachate
      in comparison with landfill leachate. 

PMID- 23948054
TI  - The consumption and recycling collection system of PET bottles: a case study of
      Beijing, China.
AB  - After studying the recycling collection system of polyethylene terephthalate
      (PET) bottles worldwide, the authors conducted an intercept survey in Beijing.
      Two separate questionnaires were issued, one questionnaire to PET bottle
      consumers and one to PET bottle recyclers. In this study, consumers are defined
      as people that consume PET-bottled beverages in their daily life. Recyclers were
      defined as those involved in the collection and recycling of PET bottles. These
      include scavengers, itinerant waste buyers, small community waste-buying depots,
      medium/large redemption depots, and recycling companies. In total, 580 surveys
      were completed, including 461 by consumers and 119 by recyclers. The authors
      found that consumption of PET bottles in Beijing was nearly 100,000 tonnes in
      2012. Age, occupation, gender, and education were identified as significant
      factors linked to PET-bottled beverage consumption, while income was not a
      significant factor. 90% Of post-consumed PET bottles were collected by informal
      collectors (i.e., scavengers and itinerant waste buyers). The survey also found
      that nearly all PET bottles were reprocessed by small factories that were not
      designed with pollution control equipment, which allows them to offer higher
      prices for waste recyclable bottles. As Beijing is trying to build a formal
      recycling collection system for recyclables, subsidies should be given to the
      formal recycling sector rather than being charged land use fees, and attention
      should also be given to informal recyclers that make their living from the
      collection of recyclables. Informal and formal sectors may work together by
      employing the scavengers and itinerant waste buyers for the formal sectors. In
      addition to the recycling of PET bottles, concern should also be allocated to
      reduce consumption, especially among young people, as they, compared to other
      groups, have a stronger demand for PET-bottled beverages and will be the main
      body of society. 

PMID- 23948055
TI  - Postentry processing of recombinant adeno-associated virus type 1 and
      transduction of the ferret lung are altered by a factor in airway secretions.
AB  - We recently created a cystic fibrosis ferret model that acquires neonatal lung
      infection. To develop lung gene therapies for this model, we evaluated
      recombinant adeno-associated virus (rAAV)-mediated gene transfer to the neonatal
      ferret lung. Unlike in vitro ferret airway epithelial (FAE) cells, in vivo
      infection of the ferret lung with rAAV1 required proteasome inhibitors to achieve
      efficient airway transduction. We hypothesized that differences in transduction
      between these two systems were because of an in vivo secreted factor that alter
      the transduction biology of rAAV1. Indeed, treatment of rAAV1 with ferret airway
      secretory fluid (ASF) strongly inhibited rAAV1, but not rAAV2, transduction of
      primary FAE and HeLa cells. Properties of the ASF inhibitory factor included a
      strong affinity for the AAV1 capsid, heat-stability, negative charge, and
      sensitivity to endoproteinase Glu-C. ASF-treated rAAV1 dramatically inhibited
      apical transduction of FAE ALI cultures (512-fold), while only reducing viral
      entry by 55-fold, suggesting that postentry processing of virus was influenced by
      the inhibitor factor. Proteasome inhibitors rescued transduction in the presence
      of ASF (~1600-fold) without effecting virus internalization, while proteasome
      inhibitors only enhanced transduction 45-fold in the absence of ASF. These
      findings demonstrate that a factor in lung secretions can influence intracellular
      processing of rAAV1 in a proteasome-dependent fashion.

PMID- 23948057
TI  - Usefulness of magnetic resonance imaging-guided vacuum-assisted breast biopsy in
      Korean women: a pilot study.
AB  - BACKGROUND: Magnetic resonance imaging (MRI)-guided vacuum-assisted biopsy is the
      technique of choice for lesions that are visible only with breast MRI. The
      purpose of this study was to report our clinical experience with MRI-guided
      vacuum-assisted biopsy in Korean women. METHODS: A total of 13 patients with 15
      lesions for MRI-guided vacuum-assisted biopsy were prospectively entered into
      this study between September 2009 and November 2011. Biopsy samples were obtained
      in a 3-T magnet using a 9-guage MRI-compatible vacuum-assisted biopsy device. We
      evaluated clinical indications for biopsy, lesion characteristics on prebiopsy
      MRI, pathologic results, and postbiopsy complication status. RESULTS: The
      clinical indications for MRI-guided vacuum-assisted biopsy were as follows:
      abnormalities in patients with interstitial mammoplasty on screening MRI (n =
      10); preoperative evaluation of patients with a recently diagnosed cancer (n =
      3); and suspicious recurrence on follow-up MRI after cancer surgery (n = 1) or
      chemotherapy (n = 1). All lesions have morphologic features suspicious or highly
      suggestive of malignancy by the American College of Radiology Breast Imaging
      Reporting and Data System category of MRI (C4a = 12, C4b = 2, C5 = 1). In two of
      the 15 lesions (13.3%, <6 mm), MRI-guided 9-gauge vacuum-assisted breast biopsy
      was deferred due to nonvisualization of the MRI findings that led to biopsy and
      the lesions were stable or disappeared on follow up so were considered benign. Of
      13 biopsied lesions, pathology revealed four malignancies (4/13, 30.8%; mean size
      15.5 mm) and nine benign lesions (9/13, 69.2%; size 14.2 mm). Immediate
      postprocedural hematoma (mean size 23.5 mm) was observed in eight out of 13
      patients (61.5%) and was controlled conservatively. CONCLUSIONS: Our initial
      experience of MRI-guided vacuum-assisted biopsy showed a success rate of 86.7%
      and a cancer diagnosis rate of 30.8%, which was quite satisfactory. MRI-guided
      vacuum-assisted breast biopsy is a safe and effective tool for the workup of
      suspicious lesions seen on breast MRI alone without major complication. This
      biopsy may contribute to the early diagnosis of breast cancer in interstitial
      mammoplasty patients in Korea.

PMID- 23948058
TI  - Subacute coagulopathy in a randomized, comparative trial of Fab and F(ab')2
      antivenoms.
AB  - BACKGROUND: Envenomation by pit vipers is associated with coagulation disorders
      including hypofibrinogenemia and thrombocytopenia. These abnormalities correct
      following antivenom treatment during the acute phase of the disease. Delayed or
      recurrent coagulation abnormalities have been reported following use of Fab
      antivenom, resulting in risk of hemorrhage or death. METHODS: We hypothesized
      that the longer plasma persistence of F(ab')2 antivenom, relative to Fab, in
      patients at risk of coagulopathy would result in decreased venonemia and
      coagulopathy one week after treatment. We conducted a Phase 2, randomized
      comparative clinical trial of rattlesnake bitten adults presenting for care in
      Tucson, Arizona, USA. Patients were randomly assigned to receive either Fab or
      F(ab')2 antivenom using a predefined treatment schedule. Endpoints included
      platelet counts, fibrinogen levels, and venom and antivenom ELISAs. Measurements
      were conducted at baseline and at various times over the following two weeks.
      RESULTS: Twelve patients were studied, with 6 randomly assigned to each treatment
      group. Early response of platelet counts, fibrinogen, and venom levels to acute
      treatment was similar in the two groups. One week following treatment, platelet
      counts and fibrinogen levels were lower in the Fab group than in the F(ab')2
      group, following a characteristic pattern that reached its lowest point
      approximately one week after initial treatment. Venom levels dropped below
      detection limits in all patients following initial treatment but subsequently
      rebounded into the measurable range in 4 of 6 Fab cases. F(ab')2 antivenom levels
      demonstrated a longer plasma persistence than Fab levels, with a less rapid drop
      during the two days following treatment. Two patients in the Fab group had
      significant adverse events involving coagulation abnormalities, for which
      additional antivenom was administered following the initial treatment period.
      CONCLUSIONS: Following the acute phase of presentation and treatment for pit
      viper envenomation, there appears to be a roughly 2-week subacute phase of the
      disease during which ongoing presence of venom may result in serious delayed or
      recurrent coagulation defects. Late hypofibrinogenemia and thrombocytopenia are
      associated with recurrent venonemia and drop in antivenom levels. This pattern
      was apparent in patients treated with Fab antivenom but was not seen among
      F(ab')2 recipients in this Phase 2 study, consistent with pharmacokinetic
      differences between the two products. Improved understanding of Fab
      pharmacokinetics is important for the management of coagulopathy-prone pit viper
      envenomation. Use of F(ab')2 antivenom may prevent recurrent venom effects, but
      larger studies are necessary for statistical confirmation of this observation.

PMID- 23948056
TI  - Comparative effect of Piper betle, Chlorella vulgaris and tocotrienol-rich
      fraction on antioxidant enzymes activity in cellular ageing of human diploid
      fibroblasts.
AB  - BACKGROUND: Human diploid fibroblasts (HDFs) undergo a limited number of cellular
      divisions in culture and progressively reach a state of irreversible growth
      arrest, a process termed cellular ageing. Even though beneficial effects of Piper
      betle, Chlorella vulgaris and tocotrienol-rich fraction (TRF) have been reported,
      ongoing studies in relation to ageing is of interest to determine possible
      protective effects that may reverse the effect of ageing. The aim of this study
      was to evaluate the effect of P. betle, C. vulgaris and TRF in preventing
      cellular ageing of HDFs by determining the activity of antioxidant enzymes viz.;
      catalase, superoxide dismutase (SOD) and glutathione peroxidase. METHODS:
      Different passages of HDFs were treated with P. betle, C. vulgaris and TRF for 24
      h prior to enzymes activity determination. Senescence-associated beta
      galactosidase (SA beta-gal) expression was assayed to validate cellular ageing.
      RESULTS: In cellular ageing of HDFs, catalase and glutathione peroxidase
      activities were reduced, but SOD activity was heightened during pre-senescence.
      P. betle exhibited the strongest antioxidant activity by reducing SA beta-gal
      expression, catalase activities in all age groups, and SOD activity. TRF
      exhibited a strong antioxidant activity by reducing SA beta-gal expression, and
      SOD activity in senescent HDFs. C. vulgaris extract managed to reduce SOD
      activity in senescent HDFs. CONCLUSION: P. betle, C. vulgaris, and TRF have the
      potential as anti-ageing entities which compensated the role of antioxidant
      enzymes in cellular ageing of HDFs.

PMID- 23948059
TI  - Flavonoids from Tetrastigma obtectum enhancing glucose consumption in insulin
      resistance HepG2 cells via activating AMPK.
AB  - Four new flavonoids including three C-glycosidic flavonoids, named tetrastigma A
      D (1-4) and five known flavones (5-9) were isolated from the herbs of Tetrastigma
      obtectum (Wall.) Planch. The structures of 1-4 were elucidated by 1D- and 2D-NMR
      and HR mass spectrometric methods. Compound 1 caused significant enhancement in
      glucose consumption by insulin-resistant HepG2 cells compared with control cells.
      In addition, compound 1 stimulated phosphorylation of AMPK, which plays an
      important role in glycometabolism. 

PMID- 23948060
TI  - Degraded limonoids and quinoline alkaloids from Dictamnus angustifolius G. Don ex
      Sweet. and their anti-platelet aggregation activity.
AB  - A new degraded limonoid, named isodictamdiol A (1), two known degraded limonoids
      (2, 3) and a new nature product of quinoline alkaloid (4) along with five known
      quinoline alkaloids (5-9) were isolated from the root bark of Dictamnus
      angustifolius G. Don ex Sweet.. Certain useful NMR data were generalized to
      determine the structures of compounds 1 and 4. The structural elucidation of
      Compound 4 was first reported herein. Compounds 1-9 showed significant inhibitory
      effects on platelet aggregation induced by ADP at 250 MUM, while Compound 4
      showed potent anti-platelet aggregation activity.

PMID- 23948061
TI  - Hematopoietic stem cell transplantation in patients with lymphomatoid
      granulomatosis: a European group for blood and marrow transplantation report.
AB  - Lymphomatoid granulomatosis (LG) is a very rare, Epstein-Barr virus-associated
      lymphoproliferative disorder of B cells. Prognosis is poor, particularly after
      relapse and no curative treatment exists. We report the results of high-dose
      therapy and autologous stem cell transplantation (ASCT) or reduced-intensity
      conditioning and allogeneic stem cell transplantation (alloSCT) in patients with
      multiply relapsed LG. A European Group for Blood and Marrow Transplantation
      survey identified 10 patients who had received 9 ASCT and 4 alloSCT. All patients
      had active disease at the time of transplantation. With a median follow-up of 5.1
      (range, 1.4 to 6.3) years, 6 patients are alive and disease-free. Two ASCT
      patients died of septicemia early after transplantation, and 1 committed suicide
      after being in continuous complete remission 19 months after ASCT. Another
      patient allografted 4 years after ASCT remained disease-free but died of severe
      graft-versus-host disease 3 months after alloSCT. High-dose therapy followed by
      ASCT and alloSCT are effective therapeutic options and should be considered in
      all patients with refractory and multiply relapsed LG.

PMID- 23948062
TI  - Host lymphocyte depletion as a strategy to facilitate early full donor chimerism
      after reduced-intensity allogeneic stem cell transplantation.
AB  - Reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell
      transplantation (RIC-alloHSCT) is associated with lower toxicity but higher rates
      of prolonged mixed chimerism than myeloablative conditioning. Decreased
      pretransplantation host T cell numbers are associated with less graft rejection
      and early full donor chimerism. To compensate for variability in
      pretransplantation host lymphocyte numbers and facilitate the achievement of
      rapid full donor chimerism, we tested a strategy of targeted lymphocyte depletion
      (TLD) using chemotherapy at conventional doses to provide cytoreduction and
      lymphocyte depletion before RIC-alloHSCT. In our study, 111 patients with
      advanced hematologic malignancies received 1 to 3 cycles of conventional-dose
      chemotherapy to reduce circulating lymphocytes to a predetermined level. Patients
      then underwent RIC-alloHSCT from HLA-matched siblings. Patients received a median
      of 2 cycles of TLD chemotherapy, resulting in a median 71% decline in CD4(+)
      count. All patients engrafted; there were no late graft failures. By day +14,
      median CD3(+) chimerism was 99% donor and was significantly associated with lower
      post-TLD CD4(+) counts (P = .012). One- and 5-year treatment-related mortality
      were 15% and 21%, respectively. At 1-year follow-up, 66% of patients had achieved
      complete remission (CR) of which 92% were not in CR at the time of
      transplantation. Overall survival at 1 and 5 years post transplantation were 66%
      and 47%, respectively.

PMID- 23948063
TI  - Inhibition of high-mobility group box 1 in lung reduced airway inflammation and
      remodeling in a mouse model of chronic asthma.
AB  - The role of high-mobility group box 1 (HMGB1) in chronic allergic asthma is
      currently unclear. Both airway neutrophilia and eosinophilia and increase in
      HMGB1 expression in the lungs in our murine model of chronic asthma. Inhibition
      of HMGB1 expression in lung in ovalbumin (OVA)-immunized mice decreased induced
      airway inflammation, mucus formation, and collagen deposition in lung tissues.
      Analysis of the numbers of CD4(+) T helper (Th) cells in the mediastinal lymph
      nodes and lungs revealed that Th17 showed greater increases than Th2 cells and
      Th1 cells in OVA-immunized mice; further, the numbers of Th1, Th2, and Th17 cells
      decreased in anti-HMGB1 antibody (Ab)-treated mice. In OVA-immunized mice, TLR-2
      and TLR-4 expression, but not RAGE expression, was activated in the lungs and
      attenuated after anti-HMGB1 Ab treatment. The results showed that increase in
      HMGB1 release and expression in the lungs could be an important pathological
      mechanism underlying chronic allergic asthma and HMGB1 might a potential
      therapeutic target for chronic allergic asthma. 

PMID- 23948064
TI  - Salsalate and adiponectin ameliorate hepatic steatosis by inhibition of the
      hepatokine fetuin-A.
AB  - Fetuin-A was recently identified as a novel hepatokine which is associated with
      obesity, insulin resistance and non-alcoholic fatty liver disease. Salsalate, a
      prodrug of salicylate with an anti-inflammatory effect and lower side effect
      profile, significantly lowers glucose and triglyceride levels, and increased
      adiponectin concentrations in randomized clinical trials. In this study, we
      examined the effects and regulatory mechanisms of salsalate and full length
      adiponectin (fAd) on fetuin-A expression, steatosis and lipid metabolism in
      palmitate-treated HepG2 cells. Incubation of hepatocytes with palmitate
      significantly increased fetuin-A and SREBP-1c expression which lead to steatosis
      and knock-down of fetuin-A by siRNA restored these changes. Salsalate
      significantly down-regulated palmitate-induced fetuin-A mRNA expression and
      secretion in a dose- and time-dependent manner. Inhibition of palmitate-induced
      fetuin-A by salsalate was mediated by AMPK-mediated reduction of NFkappaB
      activity, which was blocked by AMPK siRNA or an inhibitor of AMPK. Salsalate
      attenuated the excessive steatosis by palmitate through SREBP-1c regulation in
      hepatocytes. Furthermore, fAd also showed suppression of palmitate-induced fetuin
      A through the AMPK pathway and improvement of steatosis accompanied by
      restoration of SREBP-1c, PAPR-alpha and CD36. In preliminary in vivo experiments,
      salsalate treatment inhibited high fat diet (HFD)-induced steatosis as well as
      fetuin-A mRNA and protein expression in SD rats. In conclusion, salsalate and fAd
      improved palmitate-induced steatosis and impairment of lipid metabolism in
      hepatocytes via fetuin-A inhibition through the AMPK-NFkappaB pathway.

PMID- 23948065
TI  - MLK3 is a direct target of biochanin A, which plays a role in solar UV-induced
      COX-2 expression in human keratinocytes.
AB  - Solar UV (sUV) is an important environmental carcinogen. Recent studies have
      shown that sUV is associated with numerous human skin disorders, such as wrinkle
      formation and inflammation. In this study, we found that the isoflavone,
      biochanin A, inhibited the expression of sUV-induced COX-2, which is a well
      characterized sUV-induced enzyme, in both human HaCaT keratinocytes and JB6 P+
      mouse skin epidermal cells. Several studies have demonstrated the beneficial
      effects of biochanin A. However, its direct molecular target is unknown. We found
      that biochanin A inhibited sUV-induced phosphorylation of MKK4/JNK/c-Jun and
      MKK3/6/p38/MSK1. Mixed-lineage kinase 3 (MLK3) is an upstream kinase of MKK4 and
      MKK3/6. Thus, we evaluated the effect of biochanin A on MLK3. We found that sUV
      induced MLK3 phosphorylation was not affected, whereas MLK3 kinase activity was
      significantly suppressed by biochanin A. Furthermore, direct binding of biochanin
      A in the MLK3 ATP-binding pocket was detected using pull-down assays. Computer
      modeling supported our observation that MLK3 is a novel target of biochanin A.
      These results suggest that biochanin A exerts chemopreventive effects by
      suppressing sUV-induced COX-2 expression mediated through MLK3 inhibition. 

PMID- 23948067
TI  - Decreased myometrial p160 ROCK-1 expression in obese women at term pregnancy.
AB  - BACKGROUND: Obesity is becoming an increasing problem in obstetric practice; it
      has led to an increase in the risk of caesarean delivery, prolonged pregnancy and
      dysfunctional labour. It has been postulated that many of these problems are as a
      result of abnormal myometrial contractility. The RhoA/Rho kinase pathway is
      involved in calcium sensitisation in the myometrium during labour and contributes
      to the phosphorylation of myosin phosphatase and thus continued myosin light
      chain activity, during uterine contractility. The aim of this study therefore,
      was to investigate the effect of obesity on the expression of various components
      of the RhoA/ROCK pathway in human myometrium at term pregnancy. METHODS: Protein
      was isolated from myometrial biopsies obtained at elective caesarean section, at
      term pregnancy from obese women and from those with a normal body mass index.
      Western blotting was performed using specific primary antibodies to RhoA/ Rho
      kinase associated proteins. RESULTS: The protein expression of p160 ROCK-1 was
      significantly decreased (P < 0.001) in the myometrium from women in the obese
      cohort (n = 22) at term pregnancy, compared to women of those of normal body mass
      index (n = 15). No alteration in expression of the other proteins investigated
      was noted. CONCLUSIONS: The significant decrease in p160 ROCK-1 protein
      expression observed in the myometrium of obese women at late gestation may
      contribute to an inhibitory effect on contractility at labour, due to its
      contribution to calcium sensitisation and possibly other signalling pathways.
      These findings are relevant to the concept of compromised myometrial function in
      obese parturients.

PMID- 23948066
TI  - Neuronal nicotinic receptors as analgesic targets: it's a winding road.
AB  - Along with their well known role in nicotine addiction and autonomic physiology,
      neuronal nicotinic receptors (nAChRs) also have profound analgesic effects in
      animal models and humans. This is not a new idea, even in the early 1500s, soon
      after tobacco was introduced to the new world, its proponents listed pain relief
      among the beneficial properties of smoking. In recent years, analgesics that
      target specific nAChR subtypes have shown highly efficacious antinociceptive
      properties in acute and chronic pain models. To date, the side effects of these
      drugs have precluded their advancement to the clinic. This review summarizes the
      recent efforts to identify novel analgesics that target nAChRs, and outlines some
      of the key neural substrates that contribute to these physiological effects.
      There remain many unanswered mechanistic questions in this field, and there are
      still compelling reasons to explore neuronal nAChRs as targets for the relief of
      pain. 

PMID- 23948068
TI  - Knowledge and attitude of ICU nurses, students and patients towards the Austrian
      organ donation law.
AB  - BACKGROUND: A survey on the knowledge and attitudes towards the Austrian organ
      donation legislation (an opt-out solution) of selected groups of the Austrian
      population taking into account factors such as age, gender, level of education,
      affiliation to healthcare professions and health related studies was conducted.
      METHODS: An online survey among 3 target groups (ICU nurses, health science
      students and non health science students) was performed and results were compared
      to the answers from transplantation patients to a paper questionnaire. A total of
      8415 persons were asked to participate in the survey and 2025 (24%) persons
      correctly completed the questionnaire. 1945 online responses (ICU nurses n = 185;
      students of health sciences n = 1277; students of non-health science related
      courses n = 483) were analysed and data were compared to 80 manually filled-in
      responses from patients from a previous study. RESULTS: 84% of participants state
      that they know the Austrian organ donation legislation; this percentage varies
      significantly (p < 0.05) within the target groups and is influenced by
      demographic variables of the participants. 74% think that the law is good and 79%
      do not favour a change. Opinions and attitudes towards the legal situation are
      positively influenced by the affiliation to healthcare professions and health
      related fields of study. Interviewed persons who were aware of the legislation
      before the survey had a more positive attitude towards the existing legislation
      (77% versus 74%, p < 0.05). CONCLUSIONS: The information level on Austrian organ
      donation legislation is high. ICU nurses and those who did not know the law
      before were most critical towards the existing legislation. Therefore education
      to increase knowledge in the general population and goal-oriented efforts to
      increase awareness in the target groups should be emphasized.

PMID- 23948069
TI  - Related functions of mGlu4 and mGlu8.
AB  - Metabotropic glutamate receptors modulate glutamatergic and GABAergic
      neurotransmission. Our previous pharmacological data indicate that metabotropic
      receptor 4 (mGlu4) and metabotropic receptor 8 (mGlu8) might have related and
      overlapping functions. We explored this by analyzing the behavioral phenotypes of
      mice deficient in either (mGlu4(-/-) or mGlu8(-/-)) or both receptors (mGlu4/8(-/
      )). Our analysis focused on measures of anxiety in the open field and elevated
      zero maze, sensorimotor function on the rotarod and fear conditioning, as mGlu4
      and/or mGlu8 were shown to affect performance in these tests. mGlu8(-/-) mice
      weighed more than mGlu4/8(-/-) mice. In the open field, mGlu4(-/-) mice showed
      lower levels of anxiety than mGlu8(-/-) and mGlu4/8(-/-) mice. In the elevated
      zero maze, mGlu4(-/-) mice showed lower levels of anxiety than wild-type, mGlu8(
      /-) and mGlu4/8(-/-) mice. In the open field, but not elevated zero maze, mGlu4(
      /-) mice showed lower activity levels than wild-type, mGlu8(-/-) and mGlu4/8(-/-)
      mice. mGlu4/8(-/-) female mice showed less contextual freezing than wild-type and
      mGlu4(-/-) female mice and there was a trend toward less freezing in male
      mGlu4/8(-/-) than wild-type male mice. There were no genotype differences in cued
      fear conditioning. There were significant negative correlations between body
      weight and fall latency on the rotarod in wild-type, mGlu8(-/-) and mGlu4/8(-/-),
      but not mGlu4(-/-), mice. These data suggest related functions of mGlu4 and mGlu8
      in behavioral performance. 

PMID- 23948070
TI  - Activation of mTOR in the spinal cord is required for pain hypersensitivity
      induced by chronic constriction injury in mice.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) is known to regulate cell
      growth, and it also participates in pain transmission as has been recently
      verified in inflammatory and neuropathic pain models. The targeting of mTOR
      represents a new strategy for the control of chronic pain. In the present study,
      we investigated the effect of mTOR in the expression of PSD95 and NR2B-PSD95 or
      GluA2-PSD95 interaction ratio in a chronic constriction injury (CCI) mice model.
      METHODS: Paw mechanical withdrawal threshold (PMWT) and paw withdrawal thermal
      latency (PWTL) were respectively used to assess mechanical allodynia and thermal
      hyperalgesia after CCI operation and intrathecal injection of rapamycin. Western
      blot and co-immunoprecipitation were used to investigate the effects of rapamycin
      on the expression of PSD95 and interaction ratio of NR2B-PSD95 or GluA2-PSD95 in
      the spinal dorsal horn of mice. RESULTS: Our study demonstrated that the
      inhibition of spinal mTOR with intrathecal injections of rapamycin (1 MUg/5 MUL)
      for days 1-6 after CCI surgery led to an obvious decrease in CCI-induced
      neuropathic pain. Rapamycin significantly reduced the PMWT of CCI mice, whereas
      there was no significant effect on PWTL. The active form of the mTOR signaling
      pathway (p-mTOR, p-4EBP1 and p-p70S6k) at the spinal level remarkably increased
      in CCI mice, and rapamycin could inhibit this up-regulation. The increased
      expression of PSD95 and the interaction ratio of GluA2-PSD95 or NR2B-PSD95 could
      also be inhibited by intrathecal injection of rapamycin. CONCLUSION: These data
      suggest that the mTOR pathway is activated in the spinal dorsal horn in CCI
      induced neuropathic pain, and the intrathecal injection of rapamycin can reduce
      mechanical allodynia. Our findings indicate that spinal mTOR is an important
      component of CCI-induced neuropathic pain, and mTOR may be a potential target for
      chronic pain therapy.

PMID- 23948071
TI  - Possible beneficial effect of peroxisome proliferator-activated receptor (PPAR)-
      alpha and gamma agonist against a rat model of oral dyskinesia.
AB  - Tardive dyskinesia is a type of hyperkinetic movement disorder which consists of
      abnormal involuntary movements, characterized by orofacial movements. Previous
      studies suggest that oxidative stress and neuro-inflammation play important role
      in the pathogenesis of TD. Recently, PPAR-alpha and PPAR-Upsilon have been
      reported as neuroprotective agent in various animal models. The present study
      investigated the neuroprotective effect of PPAR-Upsilon agonist, pioglitazone (20
      and 40 mg/kg, p.o.) and PPAR-alpha agonist, fenofibrate (100 and 200mg/kg, p.o.)
      in an animal model of oral dyskinesia. Oral dyskinesia was induced by chronic
      administration of haloperidol (1 mg/kg i.p.) for 21 days. Chronic administration
      of haloperidol significantly increased vacuous chewing movements, tongue
      protrusions, facial jerking, sniffing and grooming in rats which was dose
      dependently inhibited by pioglitazone and fenofibrate. Further, it also decreased
      % retention of memory in an elevated plus maze test on day 22. Chronic
      administration of haloperidol also induced oxidative damage and neuroinflammation
      (TNF-alpha and IL-1beta) in brain regions. The fenofibrate and pioglitazone were
      able to reverse the behavioral and biochemical changes induced by haloperidol.
      Further the study proposed the antioxidant and antiinflammatory effects of both
      PPAR agonists in this model. We concluded that administration of pioglitazone and
      fenofibrate individually or in combination along with antipsychotic in the
      treatment of schizophrenia, prevent or delay the symptoms of oral dyskinesia.

PMID- 23948072
TI  - Progress in understanding fungal pathogenesis.

PMID- 23948073
TI  - Toxicological evaluation of microcystins in aquatic fish species: current
      knowledge and future directions.
AB  - Microcystins (MCs) are algal toxins produced intracellularly within the algal
      cells, and are subsequently released into the aquatic systems. An increase in the
      frequency and intensity of occurrence of harmful algal blooms has directed the
      global attention towards the presence of MCs in aquatic systems. The effects of
      MCs on fish have been verified in a number of studies including histological,
      biochemical and behavioral effects. The toxicological effects of MCs on different
      organs of fish are related to the exposure route (intraperitoneal injection,
      feeding or immersion), the mode of uptake (passive or active transport) as well
      as biotransformation and bioaccumulation capabilities by different organs. This
      paper reviews the rapidly expanding literature on the toxicological evaluation of
      MCs in fish from both field studies and controlled laboratory experimental
      investigations, integrates the current knowledge available about the mechanisms
      involved in MC-induced effects on fish, and points out future research directions
      from a cross-disciplinary perspective. In addition, the need to carry out
      systematic fish toxicity studies to account for possible interactions between MCs
      and other environmental pollutants in aquatic systems is discussed. 

PMID- 23948074
TI  - Zn-stimulated mucus secretion in the rainbow trout (Oncorhynchus mykiss)
      intestine inhibits Cd accumulation and Cd-induced lipid peroxidation.
AB  - Interest in the interactions between dietary constituents in the gut is
      increasing, but information remains sparse. In this study rainbow trout were fed
      non-enriched (186.7+/-19.0 MUg Zn g(-1) (dw)), enriched (20% increase) and hyper
      enriched Zn (200% increase) diet for 21 d followed by a single meal of Cd-spiked
      food (188.6+/-9.9 MUg Cd g(-1) (dw)). Intestinal, hepatic and renal Zn burdens
      were measured on Days 7, 14 and 21 and Cd concentrations in the same tissue were
      measured 48 h-post Cd exposure. Oxidative stress was measured as lipid
      peroxidation in dissected tissues and intestinal mucus was quantified as sialic
      acid using the thiobarbituric acid assay. Rainbow trout maintained on the hyper
      enriched Zn diet experienced significantly increased intestinal mucus secretion
      (p<0.01), were the only treatment group not to accumulate Cd in the intestine,
      and there was also no increase in intestinal oxidative damage. Conversely, fish
      fed the non-enriched and enriched Zn diets did not produce greater than basal
      levels of intestinal mucus and accumulated significantly greater concentrations
      of Cd in the intestine (p<0.01) leading to significant localised Cd-induced lipid
      peroxidation (p<0.01). High levels of mucus production correlated to lower
      incidences of lipid peroxidation (r(2)=0.54, p<0.05). These results demonstrate
      that mucus production stimulated by a high Zn diet have an inhibitory effect on
      Cd accumulation in the intestine and on Cd-induced lipid peroxidation.
      Mechanistically, it is likely that the elevated mucus production provides a
      barrier to Cd uptake. This study describes how one dietary constituent directly
      modifies the gut environment which indirectly influences the fate of another
      ingested cation.

PMID- 23948075
TI  - Phenanthrene exposure causes cardiac arrhythmia in embryonic zebrafish via
      perturbing calcium handling.
AB  - Phenanthrene (Phe) is one of the most abundant and ubiquitous polycyclic aromatic
      hydrocarbons in the aquatic environment. It is known that Phe has cardiotoxic
      effects, but knowledge concerning the mechanism of cardiac dysfunction caused by
      Phe is still limited. In this study, zebrafish embryos were exposed to
      environmentally relevant concentrations of Phe, and an increase of an irregular
      rhythm was observed in Phe treated embryos. Disordered calcium (Ca(2+)) handling
      characterized by impaired sarcoplasmic reticulum Ca(2+) uptake, and obvious
      Ca(2+) accumulation in the cytoplasm was observed in rat embryonic cardiac
      myoblasts (H9C2) exposed to Phe. The mRNA level as well as protein expression of
      the SERCA2a Ca(2+) pump in zebrafish hearts or H9C2 cells was significantly
      decreased by Phe exposure. The activity of Ca(2+)-ATPase in H9C2 cells was
      inhibited by Phe. Both the mRNA and protein levels of TBX5, a direct regulator of
      SERCA2a, were significantly decreased by Phe exposure. These results suggested
      that exposure to Phe could lead to arrhythmia in zebrafish embryos via perturbing
      the calcium handling pathway. 

PMID- 23948076
TI  - Atlantic salmon (Salmo salar L.) smolts require more than two weeks to recover
      from acidic water and aluminium exposure.
AB  - The detrimental effects of acid rain and aluminium (Al) on salmonids have been
      extensively studied, yet knowledge about the extent and rate of potential
      recovery after exposures to acid and Al episodes is limited. Atlantic salmon
      smolts in freshwater (FW) were exposed for 2 and 7-day episodes (ACID2 and ACID7,
      respectively) to low pH (5.7+/-0.2) and inorganic aluminium (Ali; 40+/-4 MUg) and
      then transferred to good water quality, control water (CW; pH 6.8+/-0.1; <14+/-2
      MUg Ali). Al accumulation on gills after 2 and 7 days of acid/Al exposure was
      35.3+/-14.1 and 26.6+/-1.8 MUg g(-1) dry weight, respectively. These elevated
      levels decreased 2 days post transfer to CW and remained higher than in control
      (CON; 5-10 MUg Ali) for two weeks. Plasma Na(+) levels in ACID2 and ACID7 smolts
      decreased to 141+/-0.8 and 138.6+/-1.4mM, respectively, and remained
      significantly lower than CON levels for two weeks post transfer to CW. Similarly,
      plasma Cl(-) levels in ACID7 smolts (124.3+/-2.8mM) were significantly lower than
      in CON, with Cl(-) levels remaining significantly lower in ACID7 (126.2+/-4.8 mM)
      and ACID2 (127.6+/-3.7 mM) than in CON following 9 and 14 days post-transfer to
      CW, respectively. ACID2 and ACID7 smolts sustained elevated plasma glucose levels
      post transfer to CW suggesting elevated stress for more than a week following
      exposure. While gill Na(+), K(+)-ATPase (NKA) activity was only slightly affected
      in ACID2 and not in ACID7 smolts in FW, acid/Al exposure resulted in a transient
      decrease in NKA activity following SW exposure in both groups. Acid/Al episodes
      had limited impact on isoform specific NKA alpha-subunit mRNA during exposure.
      However, the transfer of ACID2 and ACID7 smolts to CW showed an increase in
      NKAalpha1a mRNA (the FW isoform) and inhibited the up-regulation of NKAalpha1b
      (the SW isoform), probably resulting in higher abundance of the enzyme favouring
      ion uptake. Gill caspase 3B gene transcription did not change in acid/Al treated
      smolts, indicating no increased apoptosis in gills. ACID2 and ACID7 treatments
      resulted in lower smolt-related gill transcription of the gene encoding the tight
      junction protein claudin 10e compared to CON, while the gene encoding claudin 30
      showed lower mRNA expression only after 11 days SW exposure in ACID7 fish. Our
      data suggest that acid/Al conditions affect ion perturbations through a
      combination of alteration of the preparatory increase in paracellular
      permeability and negative impact on the SW type NKA alpha-subunit mRNA
      transcripts, and raise major concerns regarding the recovery of physiological
      disruption in smolts following acid/Al exposure. Smolts may require more than two
      weeks to fully recover from even short moderate episodes of acid/Al exposure.
      Acid/Al exposure thus probably has greater impact on salmon populations than
      previously acknowledged.

PMID- 23948077
TI  - Transcriptomic responses of European flounder (Platichthys flesus) liver to a
      brominated flame retardant mixture.
AB  - Male European flounder (Platichthys flesus) were exposed to a technical mixture
      of brominated diphenyl ethers (PDBEs, DE-71, Pentamix) that had been purified to
      remove contaminating dioxins. Controls were exposed to carrier solvent alone.
      Fish were exposed to decadally increasing concentrations of Pentamix via both
      sediment and spiked food. The GENIPOL P. flesus cDNA microarray, differentially
      expressed gene profiling (DEG) and quantitative PCR were employed to detect
      hepatic transcriptional differences between exposed fish and controls. Gene
      transcriptional changes were more sensitive to Pentamix exposure than biomarkers
      measured previously. Pentamix exposure induced transcripts coding for enzymes of
      xenobiotic metabolism (CYP1A, aldo-keto reductases) and elicited endocrine
      disruption (vitellogenin and thyroid hormone receptor alpha), with effects on
      CYP1A and VTG occurring at the highest exposure. Ontology analysis clearly showed
      dose-responsive changes indicative of oxidative stress, induction of
      mitochondrial dysfunction, and apoptosis. We conclude that exposure to PBDEs in
      both sediment and food has a significant adverse effect on a broad range of
      crucial biochemical processes in the livers of this widely distributed estuarine
      fish species, the flounder. 

PMID- 23948078
TI  - Enhanced recovery in obstetrics.

PMID- 23948079
TI  - Polyadenylation site-specific differences in the activity of the neuronal
      betaCstF-64 protein in PC-12 cells.
AB  - Recent genome-wide analyses have implicated alternative polyadenylation - the
      process of regulated mRNA 3' end formation - as a critical mechanism that
      influences multiple steps of mRNA metabolism in addition to increasing the
      protein-coding capacity of the genome. Although the functional consequences of
      alternative polyadenylation are well known, protein factors that regulate this
      process are poorly characterized. Previously, we described an evolutionarily
      conserved family of neuronal splice variants of the CstF-64 mRNA, betaCstF-64,
      that we hypothesized to function in alternative polyadenylation in the nervous
      system. In the present study, we show that betaCstF-64 mRNA and protein
      expression increase in response to nerve growth factor (NGF), concomitant with
      differentiation of adrenal PC-12 cells into a neuronal phenotype, suggesting a
      role for betaCstF-64 in neuronal gene expression. Using PC-12 cells as model, we
      show that betaCstF-64 is a bona fide polyadenylation protein, as evidenced by its
      association with the CstF complex, and by its ability to stimulate
      polyadenylation of luciferase reporter mRNA. Using luciferase assays, we show
      that betaCstF-64 stimulates polyadenylation equivalently at the two weak poly(A)
      sites of the beta-adducin mRNA. Notably, we demonstrate that the activity of
      betaCstF-64 is less than CstF-64 on a strong polyadenylation signal, suggesting
      polyadenylation site-specific differences in the activity of the betaCstF-64
      protein. Our data address the polyadenylation functions of betaCstF-64 for the
      first time, and provide initial insights into the mechanism of alternative
      poly(A) site selection in the nervous system. 

PMID- 23948080
TI  - Response of miRNAs and their targets to salt and drought stresses in cotton
      (Gossypium hirsutum L.).
AB  - MicroRNAs (miRNAs) are an important gene regulator, controlling almost all
      biological and metabolic processes, in both plants and animals. In this study, we
      investigated the effect of drought and salinity stress on the expression of
      miRNAs and their targets in cotton (Gossypium hirsutum L.). Our results show that
      the expression change of miRNAs and their targets were dose-dependent and tissue
      dependent under salinity and drought conditions. The expression of miRNAs in leaf
      was down-regulated under higher salinity stress while shows variable patterns in
      other conditions. The highest fold-changes of miRNAs were miR398 in roots with
      28.9 fold down-regulation under 0.25% NaCl treatment and miR395 in leaves with
      7.6 fold down-regulation under 1% PEG treatment. The highest up-regulation of
      miRNA targets was AST in roots with 4.7 fold-change under 2.5% PEG and the gene
      with highest down-regulation was CUC1 in leaves with 25.6 fold-change under 0.25%
      NaCl treatment. Among seven miRNA-target pairs we studied, five pairs, miR156
      SPL2, miR162-DCL1, miR159-TCP3, miR395-APS1 and miR396-GRF1, show significant
      regulation relationship in roots and leaves under salinity stress concentration.

PMID- 23948081
TI  - Salicylic acid increases the contents of glutathione and ascorbate and temporally
      regulates the related gene expression in salt-stressed wheat seedlings.
AB  - Exogenous salicylic acid (SA) significantly improved abiotic tolerance in higher
      plants, and ascorbate (ASA) and glutathione (GSH) play important roles in abiotic
      tolerance. In this study, SA (0.5mM) markedly increased the contents of ASA and
      GSH in SA-treated plants during salt stress (250mM NaCl). The transcript levels
      of the genes encoding ASA and GSH cycle enzymes were measured using quantitative
      real-time PCR. The results indicated that, during salt stress, exogenous SA
      significantly enhanced the transcripts of glutathione peroxidase (GPX1),
      phospholipid hydroperoxide glutathione peroxidase (GPX2) and dehydroascorbate
      reductase (DHAR) genes at 12h, glutathione reductase (GR) at 24h, 48h and 72h,
      glutathione-S-transferase 1 (GST1), 2 (GST2), monodehydroascorbate reductase
      (MDHAR) and glutathione synthetase (GS) at the 48h and 72h after salt stress,
      respectively. The results implied that SA temporally regulated the transcript
      levels of the genes encoding ASA-GSH cycle enzymes, resulting in the increased
      contents of GSH and ASA and enhanced salt tolerance. 

PMID- 23948082
TI  - Genome-wide analysis of endosperm-specific genes in rice.
AB  - The endosperm of the cereal crop is an important nutrient source for humans. It
      also acts as a critical integrator of plant seed growth and development. Despite
      its importance, the comprehensive understanding in regulating of endosperm
      development in rice remains elusive. Here, we performed a genomic survey
      comprising the identification and functional characterization of the endosperm
      specific genes (OsEnS) in rice using Affymetrix microarray data and Gene Ontology
      (GO) analysis. A total of 151 endosperm-specific genes were identified, and the
      expression patterns of 13 selected genes were confirmed by qRT-PCR analysis.
      Promoter regions of the endosperm-specific expression genes were analyzed by
      PLACE Signal Scan Search. The results indicated that some motifs were involved in
      endosperm-specific expression regulation, and some cis-elements were responsible
      for hormone regulation. The bootstrap analysis indicated that the RY repeat
      (CATGCA box) was over-represented in promoter regions of endosperm-specific
      expression genes. GO analysis indicated that these genes could be classified into
      12 groups, namely, transcription factor, stress/defense, seed storage protein
      (SSP), carbohydrate and energy metabolism, seed maturation, protein metabolism,
      lipid metabolism, transport, cell wall related, hormone related, signal
      transduction, and one unclassified group. Taken together, our results provide
      informative clues for further functional characterization of the endosperm
      specific genes, which facilitate the understanding of the molecular mechanism in
      rice endosperm development. 

PMID- 23948083
TI  - Molecular characterization and expression analysis of PPP1R3C in hypoxia-tolerant
      Indian catfish, Clarias batrachus (Linnaeus, 1758) under hypoxia.
AB  - Hypoxia is an important environmental stressor that leads to rapid adaptive
      changes in metabolic organization. However, the molecular mechanisms of hypoxia
      tolerance in fish remain largely unknown. The present work was focused on
      understanding the molecular mechanisms and signaling pathways that may lead to
      tolerance of Clarias batrachus to hypoxic stress. Protein phosphatase 1
      regulatory subunit 3C (PPP1R3C) is a new hypoxia-inducible factor (HIF) targeted
      gene and is regulated by HIF-1 under hypoxic conditions. Overexpression of
      PPP1R3C increases glycogen accumulation through activation of several enzymes and
      processes. In this study, for the first time, full length cDNA of PPP1R3C from C.
      batrachus was characterized and its expression pattern in the brain, liver,
      muscle and spleen under short (progressive hypoxia; PH, 1h, 6h and 12h) and long
      term (natural) hypoxic conditions was investigated. The complete cDNA of PPP1R3C
      was of 1499 bp, encoding 285 amino acid residues. The identified protein had a
      protein phosphatase 1 binding motif and a carbohydrate binding domain, thought to
      be involved in the regulation of glycogen metabolism. Short-term hypoxia exposure
      caused significant increase in PPP1R3C transcripts in the liver (6h; 6.96 fold
      and 12h; 3.91 fold) and muscle (progressive hypoxia; 3.46 fold), while, after
      long-term hypoxia exposure, significant up-regulation in the liver (7.77 fold)
      and spleen (6.59 fold) tissues was observed. No significant differences were
      observed in the brain for any time periods. Thus PPP1R3C may play an important
      role in the tolerance of C. batrachus to hypoxia.

PMID- 23948084
TI  - Splicing variants of the porcine betaine-homocysteine S-methyltransferase gene:
      implications for mammalian metabolism.
AB  - Betaine-homocysteine S-methyltransferase (BHMT) activity is only detected in the
      liver of rodents, but in both the liver and kidney cortex of humans and pigs;
      therefore, the pig was chosen as a model to define the spatial and temporal
      expression of BHMT during development. During fetal development, a total of ten
      splice variants of bhmt were expressed at varying levels across a wide range of
      porcine tissues. Two variants contained an identical ORF that encoded a C
      terminal truncated form of BHMT (tBHMT). The bhmt transcripts were expressed at
      significant levels in the liver and kidney from day 45 of gestation (G45) onward.
      The transcripts encoding tBHMT represented 5-13% of the total bhmt transcripts in
      G30 fetus, G45 liver, and adult liver and kidney cortex. The dominant structural
      feature of wild type BHMT is an (betaalpha)8 barrel, however, a modeled structure
      of tBHMT suggests that this protein would assume a horseshoe fold and lack
      methyltransferase activity. Low BHMT activity was detected in the G30 fetus, and
      slightly increased levels of activity were observed in the liver from G45 and G90
      fetuses. The bhmt promoter contained three key CpG sites, and methylation of
      these sites was significantly higher in adult lung compared to adult liver. The
      data reported herein suggest that genomic DNA methylation and variation of the 5'
      and 3' UTRs of bhmt transcripts are key regulators for the level of BHMT
      transcription and translation. 

PMID- 23948085
TI  - Prenatal diagnosis and molecular cytogenetic characterization of a de novo
      proximal interstitial deletion of chromosome 4p (4p15.2->p14).
AB  - We present prenatal diagnosis of de novo proximal interstitial deletion of
      chromosome 4p (4p15.2->p14) and molecular cytogenetic characterization of the
      deletion using uncultured amniocytes. We review the phenotypic abnormalities of
      previously reported patients with similar proximal interstitial 4p deletions, and
      we discuss the functions of the genes of RBPJ, CCKAR, STIM2, PCDH7 and ARAP2 that
      are deleted within this region. 

PMID- 23948086
TI  - A comparison of three types of stimulus material in undergraduate mental health
      nursing education.
AB  - AIMS AND OBJECTIVES: The paper discusses an innovative educational approach that
      compared the use of different textual forms as stimulus materials in the teaching
      of an introductory mental health course. BACKGROUND: Practitioners in many
      disciplines, including nursing, appreciate the value of narratives in making
      sense of experiences, challenging assumptions and enhancing learning: they enable
      exploration of reality from different perspectives and create an emotional
      resonance. Narratives help nursing students to uncover embedded meanings, values
      and beliefs; they can include written texts, illustrated texts or picture books.
      PARTICIPANTS: 180 students enrolled in an elective undergraduate nursing course.
      METHOD: This project afforded students the choice of critically analysing (a) a
      chapter from one of two autobiographies, (b) an illustrated text, or (c) an
      illustration from a picture book. Each text was a narrative account from a
      personal or carer's perspective of the experience of mental illness. Their
      written submissions were then analysed by means of a qualitative descriptive
      approach. RESULTS: In analysis of the autobiographies students tended to
      paraphrase the authors' words and summarise their experiences. Those choosing the
      illustrated text were able to link the images and text, and provide a deeper and
      more insightful level of interpretation, albeit influenced by the author's
      personal account and expressed emotions; however, those analysing a picture book
      illustration demonstrated a surprising level of critical and creative thinking,
      and their interpretations were empathetic, insightful and thoughtful. CONCLUSION:
      The use of picture books, although not a common approach in nursing education,
      appears to engage students, challenge them to think more deeply, and stimulate
      their imagination.

PMID- 23948087
TI  - The use of evidence-informed sustainability scenarios in the nursing curriculum:
      development and evaluation of teaching methods.
AB  - BACKGROUND: Climate change and resource scarcity pose challenges for healthcare
      in the future, yet there is little to raise awareness about these issues in the
      nursing curriculum and nurses are poorly equipped to practice in a changing
      climate. The aims of this paper are to describe how an evidence-informed
      'sustainability and health' scenario based on two sustainability issues (resource
      depletion and waste management) was introduced into a nursing clinical skills
      session, and to report the evaluation of the session. METHODS: Based on evidence
      from our own research on waste management, sustainable procurement and resource
      scarcity, a practical hands-on skill session was delivered to 30 second year
      student nurses as part of a scheduled clinical skills day. The session was
      observed by one of the facilitators and interactions recorded and this was
      followed by a brief questionnaire completed by participants. FINDINGS:
      Observations of the group sessions and discussion found that students
      demonstrated limited knowledge about natural resources (such as oil) used in the
      production of items used in healthcare; they engaged in discussions following the
      use of Internet resources, and were able to segregate waste appropriately. Thirty
      (100%) students completed the evaluation questionnaire, found the resources used
      in the skill session helpful, and thought that the scenarios were realistic.
      Nineteen reported being more aware of peak oil; 30 were more aware of risks to
      patient experience and service delivery if resources become unavailable; 30
      reported greater awareness of the management of waste in healthcare. Comments on
      the questionnaire indicated a high level of engagement and interest in the
      subject. CONCLUSION: The problem of climate change and resource scarcity can too
      easily be seen as a distant or intractable problem. However one way to make this
      topic real for students is through the use of clinically relevant scenarios in
      skill sessions.

PMID- 23948088
TI  - Inequity in primary and secondary preventive care for acute myocardial
      infarction? Use by socioeconomic status across middle-aged and older patients.
AB  - BACKGROUND: There has been limited research exploring socioeconomic inequity in
      targeted preventive care for acute myocardial infarction (AMI). The objective of
      this study was to examine socioeconomic disparities in the use of primary and
      secondary preventive services relevant to the identification and management of
      heart disease in a cohort of patients with AMI. METHODS: Preventive services used
      before the AMI event were examined in a cohort of 30,491 patients with first-time
      AMI in Ontario, Canada from 2010 to 2012. Using logistic regression,
      socioeconomic differences in lipid testing, glucose testing, stress testing,
      electrocardiography (ECG), and echocardiography in middle-aged and older patients
      were examined. RESULTS: For many of the services, there were no differences in
      the use of primary and secondary preventive services between patients according
      to socioeconomic status; however, a number of exceptions were found. Controlling
      for other factors, we found that for primary preventive services, low-income
      middle-aged patients had 13% (95% confidence interval [CI], 0.790-0.967) and 10%
      (95% CI, 0.812-0.997) lower odds of receiving lipid and glucose testing,
      respectively, when compared with high-income middle-aged patients. Controlling
      for other factors, we found that for secondary preventive services, low-income
      middle-aged and older patients had 24% (95% CI, 1.087-1.415) and 10% (95% CI,
      1.012-1.202) higher odds of receiving echocardiography when compared with their
      high-income counterparts. CONCLUSIONS: Socioeconomic disparities in primary and
      secondary preventive services for patients with AMI could not be demonstrated in
      many instances. However, inequities in primary preventive care were found in
      middle-aged patients receiving lipid and glucose testing, which may have
      implications for Canadian health policy to ensure healthy aging across the age
      spectrum.

PMID- 23948089
TI  - Spatial variations in polycyclic aromatic hydrocarbons concentrations at surface
      sediments from the Cyprus (Eastern Mediterranean): relation to ecological risk
      assessment.
AB  - The objective of the present study was to evaluate the distribution, sources,
      origins, and environmental risk assessment of polycyclic aromatic hydrocarbons
      (16 US EPA priority pollutants) pollution in 23 surface sediments from Cyprus
      coast. The mean total polycyclic aromatic hydrocarbons (PAHs) concentrations in
      the sediments from Gemi Konagi, Girne and Gazi Magusa areas were found 47, 52 and
      50 ng/g, respectively. Molecular ratios and principle component analysis
      indicated that PAH pollution originated mainly from fossil sources, with higher
      pyrolytic contributions. The 2-3 ring PAHs were dominant in Cyprus sediments.
      Concentrations of PAHs observed in this study were compared with available soil
      quality guidelines and the concentrations were lower than the guideline values.
      The guideline values suggested that the Cyprus sediments were likely to be not
      contaminated by toxic PAH compounds.

PMID- 23948090
TI  - Quantifying and modelling the carbon sequestration capacity of seagrass meadows-
      a critical assessment.
AB  - Seagrasses are among the planet's most effective natural ecosystems for
      sequestering (capturing and storing) carbon (C); but if degraded, they could leak
      stored C into the atmosphere and accelerate global warming. Quantifying and
      modelling the C sequestration capacity is therefore critical for successfully
      managing seagrass ecosystems to maintain their substantial abatement potential.
      At present, there is no mechanism to support carbon financing linked to seagrass.
      For seagrasses to be recognised by the IPCC and the voluntary C market, standard
      stock assessment methodologies and inventories of seagrass C stocks are required.
      Developing accurate C budgets for seagrass meadows is indeed complex; we discuss
      these complexities, and, in addition, we review techniques and methodologies that
      will aid development of C budgets. We also consider a simple process-based data
      assimilation model for predicting how seagrasses will respond to future change,
      accompanied by a practical list of research priorities. 

PMID- 23948091
TI  - Towards environmental management of water turbidity within open coastal waters of
      the Great Barrier Reef.
AB  - Water turbidity and suspended sediment concentration (SSC) are commonly used as
      part of marine monitoring and water quality plans. Current management plans
      utilise threshold SSC values derived from mean-annual turbidity concentrations.
      Little published work documents typical ranges of turbidity for reefs within open
      coastal waters. Here, time-series turbidity measurements from 61 sites in the
      Great Barrier Reef (GBR) and Moreton Bay, Australia, are presented as turbidity
      exceedance curves and derivatives. This contributes to the understanding of
      turbidity and SSC in the context of environmental management in open-coastal reef
      environments. Exceedance results indicate strong spatial and temporal variability
      in water turbidity across inter/intraregional scales. The highest turbidity
      across 61 sites, at 50% exceedance (T50) is 15.3 NTU and at 90% exceedance (T90)
      4.1 NTU. Mean/median turbidity comparisons show strong differences between the
      two, consistent with a strongly skewed turbidity regime. Results may contribute
      towards promoting refinement of water quality management protocols. 

PMID- 23948092
TI  - Mercury profiles in surface sediments from ten bays along the coast of Southern
      China.
AB  - Spatial and temporal variations of mercury (Hg) were investigated from ten
      representative bays along the coast of Southern China. The total Hg (THg) in
      surface sediments varied widely with concentrations from 25 to 264 ng/g. As a
      whole, Hg pollution in several bays occupied by busy sea traffic and industrial
      activities, such as Shantou (ST) Bay and Dapeng (DP) Bay were remarkably more
      serious than others, which reflected the direct effects of anthropogenic
      activities around the coastal areas. Hg variations in sediment cores clearly
      display upcore rising trend which obviously correlates with the trend of economic
      development and urbanization in the last five decades. No significant
      correlations were found between Hg and organic matter and particle size,
      suggesting that the distribution of Hg is not fully controlled by these
      variables.

PMID- 23948093
TI  - Interception of nutrient rich submarine groundwater discharge seepage on European
      temperate beaches by the acoel flatworm, Symsagittifera roscoffensis.
AB  - Submarine groundwater discharge (SGD) occurs in intertidal areas, representing a
      largely unquantified source of solute fluxes to adjacent coastal zones, with
      nitrogen being constantly the keynote chemical of concern. In Olhos de Agua SGD
      is present as groundwater springs or merely sub-aerial runoff. The occurrence of
      the flatworm Symsagittifera roscoffensis is described for the first time in Olhos
      de Agua in connection to seepage flows. To assess the impact of this symbiotic
      flatworm on the nitrogen associated to groundwater discharge flow at the beach,
      nitrate uptake experiments were conducted in laboratory microcosms. Our results
      show that S. roscoffensis actively uptakes nitrate at different rates depending
      on light availability, with rates ~ 10 times higher than that of its symbiotic
      microalgae alone. This supports the hypothesis that S. roscoffensis could be an
      important in situ nitrate interceptor, potentially playing a biological role on
      the transformation of groundwater-borne nitrate loads at the land-ocean boundary.

PMID- 23948094
TI  - Increased dietary cholesterol promotes enhanced mutagenesis in DNA polymerase
      kappa-deficient mice.
AB  - DNA polymerase kappa (Polkappa) bypasses planar polycyclic N2-guanine adducts in
      an error-free manner. Cholesterol derivatives may interact with DNA to form
      similarly bulky lesions. In accordance, these studies examined whether increased
      mutagenesis of DNA accompanies hypercholesterolemia in Polk-/- mice. These mice
      also carried apoE gene knockouts to ensure increased levels of plasma cholesterol
      following exposure to a high cholesterol diet. The mice carried a reporter
      transgene (the lambda-phage cII gene) for subsequent quantitative analysis of
      mutagenesis in various tissues. We observed significantly increased mutation
      frequencies in several organs of apoE-/-Polk-/- mice following a high cholesterol
      diet, compared to those remaining on a standard diet. Regardless of dietary
      regime, the mutation frequency in many organs was significantly higher in apoE-/
      Polk-/- than in apoE-/-Polk+/+ mice. As expected for polycyclic guanine adducts,
      the mutations mainly consisted of G:C transversions. The life expectancy of apoE
      /-Polk-/- mice maintained on a high cholesterol diet was reduced compared to apoE
      /-Polk+/+ mice. Overall, this study demonstrates a role for Polkappa in bypass of
      cholesterol-induced guanine lesions.

PMID- 23948095
TI  - Spermidine is required for morphogenesis in the human pathogenic fungus,
      Penicillium marneffei.
AB  - Penicillium marneffei is a thermally dimorphic fungus that is a highly
      significant pathogen of immune compromised persons living or having traveled in
      Southeast Asia. When cultured at 25 degrees C, the wild-type strain of P.
      marneffei exhibits a mycelial morphology that is marked by the development of
      specialized structures bearing conidia. Incubation of the wild type at 37 degrees
      C, however, promotes the development of a yeast form that divides by fission.
      Development of the yeast morphology in vivo appears to be requisite for
      pathogenesis. In a prior study using Agrobacterium-mediated transformation for
      random mutagenesis via T-DNA integration, we generated a morphological mutant
      (strain I6) defective in conidiation. The T-DNA insertion site in strain I6 was
      determined to be within the gene encoding S-adenosylmethionine decarboxylase
      (sadA), an enzyme critical to spermidine biosynthesis. In the present study, we
      demonstrated that strain I6 was able to grow on rich media in either the mold or
      yeast forms at 25 degrees C and 37 degrees C, respectively. However, reduced
      growth of strain I6 was observed on minimal medium at either temperature. In
      addition, strain I6 produced mycelia with impaired conidiation on minimal medium
      at 25 degrees C. Supplementation of minimal medium with spermidine restored the
      ability of strain I6 to produce conidia at 25 degrees C and promoted yeast
      development at 37 degrees C. Moreover, conidia of strain I6 exhibited poor
      germination frequencies in the absence of this polyamine. All three of these
      processes (conidiogenesis, germination, and growth) were reinstated in strain I6
      by complementation of the partially deleted of sadA gene by ectopic insertion of
      an intact wild-type copy. These results augment prior observations that
      spermidine biosynthesis is essential to normal growth, conidiogenesis, spore
      germination, and dimorphism in a variety of fungi. Given the presumption that P.
      marneffei infections are initiated following inhalation of conidia, and that
      pathogenesis is dependent upon yeast development, this study further suggests
      that the spermidine biosynthetic pathway may serve as a potential target for
      combating infections by this medically important fungus. 

PMID- 23948096
TI  - FMR1-dependent variability of ovarian aging patterns is already apparent in young
      oocyte donors.
AB  - BACKGROUND: Hypothesizing that redundant functional ovarian reserve (FOR) at
      young ages may clinically obfuscate prematurely diminished FOR (PDFOR), we
      investigated in young oocyte donors genotypes and sub-genotypes of the FMR1 gene,
      in prior studies associated with specific ovarian aging patterns, and determined
      whether they already at such young age were associated with variations in ovarian
      reserve (OR). We also investigated racial as well as FMR1 associations with
      menarcheal age in these donors. METHODS: In a cohort study we investigated 157
      oocyte donor candidates and, based on the 95% CI of AMH, divided them into normal
      age-specific (AMH greater or equal to 2.1 ng/mL; n = 121) and PDFOR (AMH < 2.1
      ng/mL; n = 36). We then assessed associations between numbers of trinucleotide
      repeat (CGGn) on the FMR1 gene and FOR (based on anti-Mullerian hormone, AMH).
      RESULTS: FMR1 did not associate with AMH overall. Amongst 36 donors with PDFOR,
      17 (42%) presented with at least one low (CGGn < 26 ) allele. Remaining donors
      with normal FOR presented with significantly more CGGn greater or equal to 26
      (73.6% vs. 26.4%; P = 0.024) and higher AMH (P = 0.012). This finding was mostly
      the consequence of interaction between FMR1 (CGGn < 26 vs. CGGn greater or equal
      to 26) and race (P = 0.013), with Asians most responsible (P = 0.009). Menarcheal
      age was in donors with normal FOR neither associated with race nor with FMR1
      status. In donors with PDFOR race was statistically associated with CGGn (P =
      0.018), an association primarily based on significantly delayed age of menarche
      in African donors with CGGn < 26 in comparison to African donors with CGGn
      greater or equal to 26 (P = 0.019), and Caucasian (P = 0.017) and Asian donors (P
      = 0.025) with CGGn < 26. CONCLUSIONS: CGGn on FMR1 already at young ages affects
      FOR, but is clinically apparent only in cases of PDFOR. Screening for low FMR1
      CGGn < 26 at young age, thus, appears predictive of later PDFOR.

PMID- 23948097
TI  - Assessment of commonly used pediatric stool scales: a pilot study.
AB  - BACKGROUND: The Bristol Stool Form Scale (BSFS) and a modified child-friendly
      version (M-BSFS) are frequently used in clinical practice and research. These
      scales have not been validated in children. 3-D stool scale models may be better
      adapted to the child's development. AIMS: To assess the usefulness of the BSFS, M
      BSFS, and a newly developed 3-D stool scale in children. METHODS: Fifty children
      were asked to rank the picture cards of the BSFS and 3-D models from hardest to
      softest and to match the pictures with descriptors for each stool type. RESULTS:
      Thirty percent of the children appropriately characterized the stools as hard,
      loose, or normal using the BSFS vs. 36.6% with the 3-D model (p=0.27).
      Appropriate correlation of stools as hard, loose, or normal consistency using the
      BSFS vs. the 3-D model by age group was: 6 to 11-year-olds, 27.5% vs. 33.3%
      (p=0.58) and 12 to 17-year-olds, 32.1% vs. 39.5% (p=0.41). Thirty-three percent
      correlated the BSFS pictures with the correct BSFS words, 46% appropriately
      correlated with the M-BSFS words, and 46% correlated the 3-D stool models with
      the correct wording. CONCLUSIONS: The BSFS and M-BSFS that are widely used as
      stool assessment instruments are not user-friendly for children. The 3-D model
      was not found to be better than the BSFS and the M-BSFS.

PMID- 23948098
TI  - The spread of mental contamination.
AB  - BACKGROUND AND OBJECTIVES: Fear of contamination can be evoked following physical
      contact with a dirty, harmful or polluted item, person, or place (contact
      contamination) or in the absence of physical contact with a contaminant (mental
      contamination). The spread of contact contamination does not degrade over
      successive degrees of removal from the contaminated source. However, to date, the
      spread of mental contamination has not been empirically investigated. This study
      aimed to examine the spread and degradation of mental contamination. METHODS: The
      paradigm of Tolin et al. (2004) was adapted. Feelings of mental contamination
      were evoked, and participants were asked to transfer these feelings to an
      uncontaminated pencil by touching it (contact condition) and without touching it
      (no contact condition). RESULTS: Seventy-two percent of participants in the
      contact condition and 48% participants in the no-contact condition reported being
      able to transfer contamination to a clean pencil, demonstrating that mental
      contamination transfers both with and without contact. In both conditions, the
      mental contamination subsequently spread to a series of 12 neutral pencils
      without degradation. CONCLUSIONS: These findings suggest that mental
      contamination can be transmitted and spread in the absence of physical contact,
      similar to contact contamination.

PMID- 23948099
TI  - Measurement of saturation processes in glutamatergic and GABAergic synapse
      densities during long-term development of cultured rat cortical networks.
AB  - The aim of this study was to clarify the saturation processes of excitatory and
      inhibitory synapse densities during the long-term development of cultured
      neuronal networks. For this purpose, we performed a long-term culture of rat
      cortical cells for 35 days in vitro (DIV). During this culture period, we labeled
      glutamatergic and GABAergic synapses separately using antibodies against
      vesicular glutamate transporter 1 (VGluT1) and vesicular transporter of gamma
      aminobutyric acid (VGAT). The densities and distributions of both types of
      synaptic terminals were measured simultaneously. Observations and subsequent
      measurements of immunofluorescence demonstrated that the densities of both types
      of antibody-labeled terminals increased gradually from 7 to 21-28 DIV. The
      densities did not show a further increase at 35 DIV and tended to become
      saturated. Triple staining with VGluT1, VGAT, and microtubule-associated protein
      2 (MAP2) enabled analysis of the distribution of both types of synapses, and
      revealed that the densities of the two types of synaptic terminals on somata were
      not significantly different, but that glutamatergic synapses predominated on the
      dendrites during long-term culture. However, some neurons did not fall within
      this distribution, suggesting differences in synapse distribution on target
      neurons. The electrical activity also showed an initial increase and subsequent
      saturation of the firing rate and synchronized burst rate during long-term
      culture, and the number of days of culture to saturation from the initial
      increase followed the same pattern under this culture condition. 

PMID- 23948101
TI  - Throwing the banana away and keeping the peel: neuroelectric responses to
      unexpected but physically feasible action endings.
AB  - Integrative semantic processing and mirror-neuron system activation in response
      to incongruence detection during action observation have so far been investigated
      only through paradigms that involve unfeasible action endings, introduction of
      extraneous objects or synthetic pictures. The ecological validity of the reported
      effects, particularly modulation of the N400 event-related potential (ERP),
      therefore remains questionable. To address this shortcoming, we investigated the
      ERPs evoked by physically feasible and naturalistic but unexpected action
      endings. We hypothesized that in comparison to existing work our more realistic
      scenarios would elicit slower processing, due to engagement of deeper analysis as
      opposed to fast detection based on automatic processes. ERPs were recorded in 14
      healthy participants in response to 60 sequences, each containing three pictures,
      the last of which could be an expected or unexpected action ending. The N400 was
      larger for the first image compared to the others, and the LPP was enhanced for
      unexpected endings. Source localization implicated anterior fronto-temporal and
      temporo-parietal junction regions in generation of these potentials. Our findings
      challenge the view that the N400 universally indices verbal and action-perception
      incongruence detection, and point to situation-contingent effects which, in the
      case of subtle violations, are reflected in later activity components,
      speculatively reflecting recourse to the "mentalizing" system. 

PMID- 23948100
TI  - MicroRNA overexpression increases cortical neuronal vulnerability to injury.
AB  - Previously we reported that several microRNAs (miRNA) are upregulated following
      experimentally induced traumatic brain injury (TBI) using both in vivo and in
      vitro approaches. Specific miRNAs were found to be sensitive to therapeutic
      hypothermia and may therefore be important targets for neuroprotective
      strategies. In this study we developed plasmid constructs that overexpress
      temperature sensitive miRNAs: miR-34a, miR-451, and miR-874. These constructs
      were transfected into cultured cortical neurons that were subjected to stretch
      injury using a cell injury controller device. Levels of expression of genes
      associated with stress, inflammation, apoptosis and transcriptional regulation
      were measured by qRT-PCR. mRNA levels of cytokines interleukin 1-beta (IL1-beta)
      and tumor necrosis factor alpha (TNF-alpha) as well as heat shock protein 70
      (HSP70) and Caspase 11 were found to be increased up to 24 fold higher than
      controls in cells overexpressing these miRNAs. After moderate stretch injury, the
      expression of IL1-beta, TNF-alpha, HSP70 and Caspase 11 all increased over
      control levels found in uninjured cells suggesting that overexpression of these
      miRNAs increases cellular vulnerability. miR-34a directly inhibits Bcl2 and XIAP,
      both anti-apoptotic proteins. The observed increase in Caspase 11 with over
      expression of miR-34a indicates that miR-34a may be inducing apoptosis by
      reducing the levels of anti-apoptotic proteins. miR-34a is predicted to inhibit
      Jun, which was seen to decrease in cells overexpressing this miRNA along with
      Fos. Over expression of several miRNAs found to be induced by TBI in vivo (miR
      34a, miR-451 and miR-874) leads to increased vulnerability in transfected
      neurons. Therapeutic hypothermia blunts the expression of these miRNAs in vivo
      and antisense silencing could be a potential therapeutic approach to targeting
      the consequences of TBI. 

PMID- 23948102
TI  - Transplantation of autologous bone marrow mesenchymal stem cells in the treatment
      of complete and chronic cervical spinal cord injury.
AB  - Neuronal injuries have been a challenging problem for treatment, especially in
      the case of complete and chronic cervical spinal cord injury (SCI). Recently,
      particular attention is paid to the potential of stem cell in treating SCI, but
      there are only few clinical studies and insufficient data. This study explored
      the efficacy of autologous bone marrow mesenchymal stem cells (BMMSCs)
      transplantation in the treatment of SCI. Forty patients with complete and chronic
      cervical SCI were selected and randomly assigned to one of the two experimental
      groups, treatment group and control group. The treatment group received BMMSCs
      transplantation to the area surrounding injury, while the control group was not
      treated with any cell transplantation. Both the transplant recipients and the
      control group were followed up to 6 months, postoperatively. Preoperative and
      postoperative neurological functions were evaluated with AIS grading, ASIA score,
      residual urine volume and neurophysiological examination. Results showed that in
      the treatment group 10 patients had a significant clinical improvement in terms
      of motor, light touch, pin prick sensory and residual urine volume, while nine
      patients showed changes in AIS grade. Neurophysiological examination was
      consistent with clinical observations. No sign of tumor was evident until 6
      months postoperatively. In the control group, no improvement was observed in any
      of the neurological functions specified above. BMMSCs transplantation improves
      neurological function in patients with complete and chronic cervical SCI,
      providing valuable information on applications of BMMSCs for the treatment of
      SCI. 

PMID- 23948103
TI  - Quantitative studies of caspase-3 catalyzed alphaII-spectrin breakdown.
AB  - Under various physiological and patho-physiological conditions, spectrin
      breakdown reactions generate several spectrin breakdown products (SBDPs)-in
      particular SBDPs of 150 kDa (SBDP150) and 120 kDa (SBDP120). Recently, numerous
      studies have shown that reactions leading to SBDPs are physiologically relevant,
      well regulated, and complex. Yet molecular studies on the mechanism of the SBDP
      formation are comparatively scarce. We have designed basic systems to allow us to
      follow the breakdown of alphaII-spectrin model proteins by caspase-3 in detail
      with gel electrophoresis, fluorescence and mass spectrometry methods. Amongst the
      predicted and reported sites, our results show that caspase-3 cleaves after
      residues D1185 and D1478, but not after residues D888, D1340 and D1475. We also
      found that the cleavage at these two sites is independent of each other. It may
      be possible to inhibit one site without affecting the other site. Cleavage after
      residue D1185 in intact alphaII-spectrin leads to SBDP150, and cleavage after
      D1478 site leads to SBDP120. Our results also show that the cleavage after the
      D1185 residue is unusually efficient, with a kcat/KM value of 40,000 M(-1) s(-1),
      and the cleavage after the D1478 site is more similar to most of the other
      reported caspase-3 substrates, with a kcat/KM value of 3000 M(-1) s(-1). We
      believe that this study lays out a methodology and foundation to study caspase-3
      catalyzed spectrin breakdown to provide quantitative information. Molecular
      understanding may lead to better understanding of brain injuries and more precise
      and specific biomarker development.

PMID- 23948104
TI  - Early exercise training improves ischemic outcome in rats by cerebral
      hemodynamics.
AB  - This study examined whether very early initiated physical rehabilitation (VEIPR),
      as a recommended therapy for postischemia, could improve motor performance and
      cerebral blood flow (CBF). Adult male rats with ischemic injury caused by middle
      cerebral artery occlusion (MCAO) were trained to run on a treadmill for 30min per
      day at 12m/min. Through such exercise training for 3 days, the ischemic rats
      exhibited increased motor function and decreased infarct volume, as measured by a
      behavioral score and 2,3,5-triphenyltetrazolium chloride (TTC) staining method,
      as well as accelerated CBF, as detected with laser speckle imaging (LSI).
      Furthermore, to determine whether the observed improved CBF provided the
      protective factor for motor function recovery, we investigated the apoptosis of
      ischemic rat brain microvascular endothelial cells (rBMECs), which accepted the
      mechanical force of CBF directly, under flow intervention. The findings indicated
      that a modest flow decreased cell apoptosis in the ischemic condition and that
      this effect is magnitude dependent, as excessive flow increased apoptosis. 

PMID- 23948105
TI  - Epigenetics of cellular reprogramming.
AB  - Cells are constantly changing their state of equilibrium in response to internal
      and external stimuli. These changes in cell identity are driven by highly
      coordinated modulation of gene expression. This coordinated regulation is
      achieved in large part due to changes in the structure and composition of the
      chromatin, driven by epigenetic modulators. Recent discoveries in cellular and
      genomic reprogramming have highlighted the importance of chromatin modifications
      to reach and uphold the fidelity of target cell states. In this review, we focus
      on the latest work addressing the mechanisms surrounding the epigenetic
      regulation of various types of reprogramming, including somatic cell nuclear
      transfer (SCNT), cell fusion and transcription factor-induced and microRNA
      induced pluripotency. The studies covered herein showcase the interplay between
      these epigenetic pathways, and highlight the importance of furthering our
      understanding of these connections to form a clearer picture of the mechanisms
      underlying stable cell fate transitions. 

PMID- 23948106
TI  - Prognostic association of HbA1c and fasting plasma glucose with reduced kidney
      function in subjects with and without diabetes mellitus. Results from a
      population-based cohort study from Germany.
AB  - OBJECTIVE: To determine the risk for incident reduced kidney function (RKF) of
      subjects with pre-diabetes (impaired fasting glucose (IFG, 5.6-6.9 mmol/L)) or
      HbA1c-defined pre-diabetes (5.7%-6.4%) and to determine dose-response
      relationships of fasting glucose and HbA1c with RKF in subjects with manifest
      diabetes mellitus. METHOD: In a German population-based cohort, recruited 2000
      2002 with ages 50-74 years, log-binomial regression was used to estimate relative
      risks (RR) with 95% confidence intervals (95%CI) and restricted cubic splines to
      plot dose-response relationships. RESULTS: During 8 years of follow-up, 678 of
      3538 study participants developed primary RKF. Although RKF risk factor
      prevalences and RKF incidences were higher in subjects with pre-diabetes than in
      subjects with normal FPG and/or HbA1c levels, an increased risk did not persist
      after adjusting for established cardiovascular risk factors (RR(IFG): 0.97 (95%
      CI: 0.75-1.25) and RR(HbA1c-defined pre-diabetes): 1.03 (95% CI: 0.86-1.23)). In
      subjects with manifest diabetes, RKF risk increased linearly to a more than three
      fold risk with increasing fasting glucose and HbA1c levels (at HbA1c>6.4%).
      CONCLUSION: This study provides further evidence that pre-diabetes may not
      directly contribute to the development of kidney disease. Subjects with pre
      diabetes might nevertheless profit from preventive efforts reducing their
      cardiovascular risk profile because cardiovascular and kidney disease share
      common risk factors.

PMID- 23948107
TI  - Elementary school practices and children's objectively measured physical activity
      during school.
AB  - OBJECTIVE: To examine the relation of physical activity practices covering
      physical education (PE), recess, and classroom time in elementary schools to
      children's objectively measured physical activity during school. METHODS:
      Participants were 172 children from 97 elementary schools in the San Diego, CA
      and Seattle, WA USA regions recruited in 2009-2010. Children's moderate-to
      vigorous physical activity (MVPA) during school was assessed via accelerometry,
      and school practices were assessed via survey of school informants. Multivariate
      linear mixed models were adjusted for participant demographics and unstandardized
      regression coefficients are reported. The 5 practices with the strongest
      associations with physical activity were combined into an index to investigate
      additive effects of these practices on children's MVPA. RESULTS: Providing >= 100
      min/week of PE (B=6.7 more min/day; p=.049), having <= 75 students/supervisor in
      recess (B=6.4 fewer min/day; p=.031), and having a PE teacher (B=5.8 more
      min/day; p=.089) were related to children's MVPA during school. Children at
      schools with 4 of the 5 practices in the index had 20 more min/day of MVPA during
      school than children at schools with 0 or 1 of the 5 practices (p<.001).
      CONCLUSIONS: The presence of multiple school physical activity practices doubled
      children's physical activity during school.

PMID- 23948108
TI  - Impact of atrial fibrillation on early complications and one year-survival after
      cardioverter defibrillator implantation: results from the German DEVICE registry.
AB  - AIMS AND OBJECTIVE: Outcome data of patients with implantable cardioverter
      defibrillators (ICD) and atrial fibrillation (AF) are conflicting. The German
      DEVICE registry aims to add further information on this particular cohort.
      METHODS AND RESULTS: The German DEVICE registry is a nationwide prospective
      multicenter database of ICD implantations. 3261 patients are included (81% males,
      2701 (82.8%) first ICD implantations, 560 (17.2%) ICD replacements). Cardiac
      resynchronization therapy (CRT-D) was performed in 882 patients (27.0%). Sinus
      rhythm (SR) was present in 2654 (81.4%) and atrial fibrillation (AF) in 607
      (18.6%). Left ventricular ejection fraction (LVEF) did not differ between groups
      (SR 32.3%, AF 30.4%; p = 0.09). AF patients were older (AF 70.9 versus SR 63.9
      years; p < 0.0001), presented with more co-morbidities (diabetes, hypertension,
      chronic kidney disease; all p < 0.001). In-hospital complications were not
      significantly different between groups (p = 0.58). Follow-up information after
      one year was available in 2967 patients (91%). One-year overall mortality after
      first ICD implantation was 4.9% for SR and 11.2% for AF patients (p < 0.0001);
      mortality one year after ICD replacement was 8.4% for SR and 12.0% for AF (p =
      0.34). No statistically significant difference between SR and AF patients
      receiving a CRT device was observed (SR 6.9%, AF 10.7%, p = 0.16) in terms of one
      year mortality. CONCLUSION: The German DEVICE registry demonstrates that patients
      with AF who receive ICD devices are older, have more co-morbidity and more severe
      heart failure. AF carries an independent 1.39 fold risk (95% CI 1.02-1.89) of
      death after one year in patients only with first ICD implantation.

PMID- 23948109
TI  - Influence of socioeconomic status on therapy and prognosis after an acute heart
      failure episode.

PMID- 23948110
TI  - Drug eluting balloon versus drug eluting stent in percutaneous coronary
      interventions: insights from a meta-analysis of 1462 patients.
AB  - BACKGROUND: Drug eluting balloons (DEB) have been developed to overcome the
      limitations of drug eluting stents (DES), but clinic results of various DEB
      studies are still not consistent. Thus, we performed a meta-analysis to compare
      outcomes of DEB and DES for the treatment of coronary artery disease (CAD).
      METHODS: Medline/Web databases were searched for studies comparing DEB and DES
      for obstructive CAD, reporting late lumen loss (LLL) and rates for overall
      mortality, myocardial infarction (MI), stent thrombosis (ST) and target lesion
      revascularization (TLR). RESULTS: 8 studies (1462 patients) were included in the
      meta-analysis. Compared with DES, DEB treated patients showed non-significantly
      higher LLL (weighted mean difference [WMD] 0.32, 95% confidence interval [CI] 
      0.15 to 0.78, P=0.18) and non-significantly higher rate of binary restenosis
      (odds ratio [OR] 1.40 [0.68-2.48], P=0.36). Mortality (OR 1.13[0.54-2.37],
      P=0.74), MI (OR 0.95, [0.50-1.80], P=0.87), ST (OR 1.12, [0.34-4.19], P=0.77) and
      TLR rates (OR 1.19[0.60-2.38], P=0.61) were similar between the 2 treatments. A
      pre-specified meta-regression analysis showed that LLL WMD and TLR OR were
      inversely correlated to the prevalence of diabetes (P<0.0001) and directly
      correlated to reference coronary diameters (P<0.001). CONCLUSIONS: The present
      meta-analysis showed that compared to DES, DEB use resulted in similar clinical
      efficacy and safety. Thus DEB could be considered a reasonable alternative to DES
      for the treatment of CAD in selected clinical settings (Clinicaltrials.gov
      identifier: NCT01760200).

PMID- 23948111
TI  - Incremental value of adenosine stress cardiac magnetic resonance in coronary
      artery disease detection.
AB  - INTRODUCTION: Cardiac magnetic resonance myocardial perfusion imaging (CMR-MPI)
      is considered a state-of-the-art non-invasive modality for ischemia detection but
      its additive value in a multiple-test strategy in patients with suspected
      coronary artery disease (CAD) is not fully validated. We aimed to evaluate CMR
      MPI integration with exercise treadmill test (ETT) for the diagnostic workup of
      patients with suspected CAD, having invasive fractional flow reserve (FFR) as
      reference standard. METHODS: In this prospective single-center study, patients
      with suspected CAD underwent sequential ETT, CMR-MPI and X-ray invasive coronary
      angiography (XA). Significant CAD was defined by the presence of stenosis >40%
      with FFR <= 0.8 in vessels >2 mm or >=90% stenosis/occlusion. RESULTS: 80
      symptomatic patients (68% male, 61 +/- 8 years) were enrolled. Compared to ETT,
      CMR-MPI showed similar sensitivity (81%) and higher specificity (93 vs. 58%, p <
      0.001) for CAD detection (prevalence = 46%) translating into better diagnostic
      performance (AUC 0.87 vs. 0.70; p = 0.002). CMR-MPI improved accuracy
      independently of ETT in all patients with high pre-test probability and in
      intermediate-probability patients but those with a clearly positive-ETT (symptoms
      + ST-shift), in whom ETT correctly identified CAD. In the low-probability group
      CMR-MPI was useful as a gatekeeper for XA after a positive-ETT. The best
      integrating protocol achieved a global accuracy of 89% (AUC 0.88) and was clearly
      superior to an approach based solely in ETT (AUC 0.70, p < 0.001), yet similar to
      isolated CMR-MPI (AUC 0.87, p = ns). CONCLUSIONS: CMR-MPI has high sensitivity
      and specificity for CAD detection and may be combined with ETT in a diagnostic
      workflow aiming to increase accuracy and reduce the number of unnecessary
      catheterizations.

PMID- 23948112
TI  - Depression, antidepressants, and the risk of coronary heart disease: a population
      based cohort study.
AB  - BACKGROUND: Evidence supporting a predictive role for depression in the
      pathgenesis of coronary heart disease (CHD) has mainly come from studies in
      Western countries. Conflicting data exist regarding the association between
      antidepressant use and the incidence of CHD. This population-based study tracked
      the risk of composite coronary events in a cohort with newly diagnosed depression
      compared to an age- and gender-matched cohort without depression. The association
      between antidepressant use and risk of coronary events in individuals with
      depression was also investigated. METHODS: In total, 39,685 individuals (7937
      with depression and 31,748 without depression) aged 20-99 years selected from a
      random sample of 10(6) beneficiaries of the Taiwan National Health Insurance
      Program were followed up for up to 9 years with a median follow-up period of 8.76
      years. Coronary events were identified using the International Classification of
      Diseases, Ninth Revision, Clinical Modification diagnostic and procedure codes.
      Antidepressant use was identified using Anatomical Therapeutic Chemical
      classification codes. RESULTS: The multivariable-adjusted hazard ratio (HR) for
      newly detected coronary events was 1.49 (95% confidence interval (CI)=1.29-1.74,
      p<0.001) for individuals with depression compared to age- and gender-matched
      individuals without depression. Use of selective serotonin reuptake inhibitors
      and tricyclic antidepressants did not significantly impact the risk of the
      composite coronary events among individuals with depression. CONCLUSIONS:
      Depression is associated with an increased risk for CHD. No evidence supporting
      an association between antidepressants and coronary events was found.

PMID- 23948113
TI  - Severity of acute heart failure in men according to diabetes mellitus: the role
      of testosterone and renal dysfunction.

PMID- 23948114
TI  - Phospholipase A2 expression in coronary thrombus is increased in patients with
      recurrent cardiac events after acute myocardial infarction.
AB  - OBJECTIVES: Intracoronary thrombus is a source of active lipid mediators
      including eicosanoids that play a critical role in the pathogenesis of acute
      myocardial infarction (AMI). Eicosanoids are derived from arachidonic acid
      generated by phospholipase A(2) (PLA(2)). This study examined whether PLA(2) is
      expressed in the aspirated coronary thrombus and whether PLA(2) expression in the
      thrombus may be related to recurrence of cardiac events and development of
      atherosclerosis in the culprit coronary artery after AMI. METHODS: Intracoronary
      thrombus was obtained using an aspiration catheter from 48 patients with AMI, who
      had successful emergent treatment with percutaneous coronary intervention (PCI).
      Repeated intravascular ultrasound in the culprit coronary artery was performed at
      emergent PCI and 6 months later in a subgroup of 20 patients. RESULTS: There was
      a higher prevalence of cells in the thrombus that were immunopositive to group
      IIA, IVA, V and X PLA2s in patients with (n = 11) than without (n = 37) cardiac
      events during 6 months of follow-up (P < 0.05 for all). The prevalence of the
      cells that were immunopositive to group IIA, IVA and V PLA2s in the thrombus was
      significantly associated with the percent increase in atheroma volume (r = 0.60,
      0.55 and 0.45, respectively, P < 0.05 for all) after 6 months in the native
      coronary segment distal to the culprit coronary lesion. CONCLUSION: PLA(2)
      expression in coronary thrombus is associated with recurrence of cardiac events
      and development of atherosclerosis in the culprit coronary artery in AMI
      survivors.

PMID- 23948115
TI  - Anticoagulation in "real world" patients with atrial fibrillation in Italy:
      results from the ISPAF (Indagine Sicoa Paziente Con Fibrillazione Atriale) survey
      study.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with a high risk of stroke and
      other thrombo-embolic events and their prevention relies on antithrombotic
      therapy, at present mainly with vitamin K antagonists (VKA). The aim of this
      study was to provide an overall picture on the extent to which current
      recommendations on oral anticoagulation (OAC) therapy with VKA in AF correspond
      to actually prescribed OAC in an unselected, real world, population of
      consecutive patients with AF in Italy. Secondary objective was to assess the rate
      of "optimal" anticoagulation. METHODS: Sixty-three cardiology units located in
      different geographic areas of Italy enrolled a total of 2046 outpatients with
      nonvalvular AF (54% males and 46% females, age 73.3+/-10.2 years). RESULTS: OAC
      with VKAs was prescribed in 1394 (68%) of patients and was progressively more
      frequent on going from paroxysmal (46%) to persistent (71%) and permanent AF
      (78%)(P<0.001). A high prescription rate (88%) occurred in patients with CHA2DS2
      VASc >2. In patients with CHA2DS2-VASc=0 and HAS-BLED<3, still 59% were on OAC,
      whereas in 33% of patients with CHA2DS2-VASc >=2 and HAS-BLED<3, OAC therapy was
      not prescribed. In patients with CHA2DS2-VASc >=2 and HAS-BLED>3, the preference
      was towards OAC prescription. 66% of patients were at target for INR.
      CONCLUSIONS: The ISPAF study shows that in an Italian population of real world
      patients with AF adherence to current guidelines on OAC therapy based on stroke
      risk scoring system is rather high, although rate of prescription should be
      increased. However, contrary to recommendations, in a high proportion of low-risk
      patients OAC therapy is still prescribed, and this might expose patients to
      unjustified risks.

PMID- 23948116
TI  - Angiographic assessment of myocardial perfusion in Tako-Tsubo syndrome.
AB  - OBJECTIVES: To angiographically assess myocardial perfusion in patients with Tako
      Tsubo syndrome (TTS) in comparison with control individuals and patients with ST
      elevation myocardial infarction (STEMI). BACKGROUND: Coronary microvascular
      dysfunction has been proposed as the pathophysiological mechanism underlying TTS.
      METHODS: We retrospectively selected consecutive TTS patients showing typical
      left ventricular (LV) apical dysfunction admitted to our Department in the period
      2007-2011 (n=25). We also enrolled an age and gender-matched control group
      showing normal coronary arteries (CTR, n=25), patients with STEMI undergoing
      primary percutaneous intervention with myocardial reperfusion (SR, n=25) or
      microvascular obstruction (SMVO, n=25). TIMI flow, TIMI frame count (TFC) and
      both qualitative and quantitative myocardial blush grade in LV apex were
      assessed. Specifically, myocardial perfusion was quantitatively evaluated using
      'Quantitative Blush Evaluator' (QuBE), an open source software previously
      validated in the setting of STEMI. RESULTS: In TTS, TIMI flow on the LAD was
      significantly lower and TFC significantly higher compared to CTR and SR (p=0.008
      for both), while it did not significantly differ compared to SMVO (p=0.06). In
      TTS, MBG was significantly lower than that in CTR and SR (p=0.001 for both),
      while it was significantly higher than that in SMVO (p<0.001). In TTS, QuBE score
      was significantly lower than that in CTR and SR (p=0.001 for both) and higher
      than in SMVO (p=0.02). CONCLUSIONS: Our data indicate that myocardial perfusion
      assessed during angiography is more impaired in patients with TTS than in
      patients with STEMI exhibiting myocardial reperfusion, while it is less impaired
      than in patients with STEMI exhibiting MVO.

PMID- 23948117
TI  - Early lead exposure (<3 years old) prospectively predicts fourth grade school
      suspension in Milwaukee, Wisconsin (USA).
AB  - School suspensions are associated with negative student outcomes. Environmental
      lead exposure increases hyperactivity and sensory defensiveness, two traits
      likely to increase classroom misbehavior and subsequent discipline. Childhood
      Blood Lead Level (BLL) test results categorized urban fourth graders as exposed
      (2687; lifetime max BLL 10-20 ug/dL) or unexposed (1076; no lifetime BLL >=5
      ug/dL). Exposed children were over twice as likely as unexposed children to be
      suspended (OR=2.66, 95% CI=[2.12, 3.32]), controlling for covariates. African
      American children were more likely to be suspended than white children, but lead
      exposure explained 23% of the racial discipline gap. These results suggest that
      different rates of environmental lead exposure may contribute to the racial
      discipline gap.

PMID- 23948118
TI  - The effects of 11-ketotestosterone on ovarian physiology of previtellogenic
      captive hapuku (Polyprion oxygeneios).
AB  - The present study investigated, for the first time in a perciform teleost, the
      effects of in vivo 11-ketotestosterone (11-KT) treatment using slow-release
      implants on ovarian development and gonadotropin receptor mRNA levels in captive
      previtellogenic females of hapuku (Polyprion oxygeneios). At the
      cellular/functional level, ovarian development and ovarian and hepatic total
      lipid levels were examined. At the molecular level, transcript abundance of
      ovarian follicle-stimulating hormone receptor (FSH-R) and luteinizing hormone
      receptor (LH-R) was measured. Additionally, cyclic adenosine monophosphate (cAMP)
      levels in ovarian fragments from placebo and 11-KT implanted fish incubated with
      or without human chorionic gonadotropin (hCG) in vitro were compared between
      groups. There were no significant differences between treatments with regard to
      oocyte size and lipid contents of liver and ovary. Messenger RNA levels of FSH-R
      and LH-R were significantly lower in the treated females. Similarly, cAMP levels
      were significantly lower in the ovarian fragments of the 11-KT implanted females.
      These results suggest that 11-KT specifically, but possibly androgens in general,
      may not have an important function in regulating gonadal development of
      previtellogenic female hapuku; indeed, if anything, 11-KT appeared to have a
      detrimental effect and its use will not be beneficial in advancing sexual
      maturity of hapuku in aquaculture. 

PMID- 23948119
TI  - Evidence for a regulatory loop between cholecystokinin (CCK) and tryptic enzyme
      activity in Atlantic cod larvae (Gadus morhua).
AB  - In order to maximize protein digestion, the release of enzymes into the gut lumen
      is closely controlled by a regulatory loop. Cholecystokinin (CCK) is among the
      enteric hormones that play a key role in the control of digestive enzyme
      secretion, but its role in first-feeding larvae is still unclear and may differ
      between species. However, in all marine fish larvae that have not developed a
      stomach by first-feeding, trypsin is the most important proteolytic enzyme. In
      order to examine the regulation and feedback mechanisms in the gut of larval cod,
      we therefore studied the interactions between cholecystokinin and tryptic enzyme
      activity following the administration of solutions containing test substances
      directly into the gut. We tube-fed a single dose of physiological saline solution
      containing either CCK, CCK antagonist, trypsin inhibitor, phytohemagglutinin
      (PHA; a possible trigger for the digestive response) or physiological saline
      alone, while a further control group was left untreated. We then followed the
      response in CCK and tryptic enzyme activity for 0.5-8h after the administration.
      We performed the experiment on larvae at 26day post first-feeding, which is
      before the stomach has evolved and the size of the larvae allows easier handling.
      Individual larvae were analyzed for CCK and tryptic enzyme activity using
      radioimmunoassay and fluorimetric techniques respectively. Both factors varied
      over time in the untreated control group, possibly due to an endogenous daily
      rhythm. The higher CCK levels at 4h and 8h in the saline-injected group may be
      caused by reflexes initiated by distension of the gut. An increase in tryptic
      enzyme activity after injection of CCK supports the hypothesis that this hormone
      plays a part in the release of pancreatic enzymes in larval cod at this
      developmental stage. However, administration of a CCK antagonist and a trypsin
      inhibitor did not reveal conclusive results, probably due to the relatively low
      concentrations used. The response in tryptic activity in the PHA group was
      similar to the administration of CCK, pointing towards a stimulatory effect of
      PHA on the proteolytic enzyme capacity of cod larvae. 

PMID- 23948120
TI  - Methylmercury impairs motor function in early development and induces oxidative
      stress in cerebellar granule cells.
AB  - Environmental toxicants such as methylmercury play a critical role in the
      pathogenesis of many neurodevelopmental disorders. Environmental exposure to
      methylmercury frequently occurs at low doses, most frequently through fish
      consumption. Although the general population is at risk for exposure, pregnant
      women and young children are the most vulnerable. A common symptom of perinatal
      exposure to methylmercury is increased sensory (visual) deficits, motor
      impairment, and an overall cognitive decline. Research has indicated that the
      developing cerebellum, specifically the cerebellar granular layer, is
      particularly vulnerable to methylmercury neurotoxicity. This review examines the
      effects of low-level methylmercury exposure on motor coordination. We
      specifically focus on the role of cerebellar granule cells in methylmercury
      neurotoxicity. We suggest that methylmercury induces oxidative stress in
      cerebellar granule cells, which subsequently results in apoptotic cell death.
      Understanding the mechanism by which methylmercury induces toxicity within the
      developing brain will allow for enhanced treatments and potential reversal of the
      detrimental effects. 

PMID- 23948121
TI  - Endoplasmic reticulum stress signaling involvement in manganese-induced nerve
      cell damage in organotypic brain slice cultures.
AB  - Overexposure to manganese (Mn) has been known to induce neuronal damage. However,
      the mechanisms underlying the neurotoxicity of Mn are still incompletely
      understood but seem to involve endoplasmic reticulum (ER) stress. The current
      study investigated whether ER stress signaling was involved in Mn-induced
      neurotoxicity in organotypic brain slices. After the brain slices were
      respectively exposed to 400MUM Mn for 0, 6, 12, 18, 24h, there was a time
      dependent increase in apoptotic cell death in slices and levels of lactate
      dehydrogenase (LDH) in the culture medium. Moreover, Mn was found to upregulate
      GRP78/94, CHOP and caspase-12 expression. Furthermore, PERK phosphorylation, PERK
      mediated phosphorylation of eIF2a and ATF4 mRNA expression increased. IRE1
      activation and Xbp1 mRNA splicing also increased. However, ATF6 p90 levels did
      not change. The findings clearly demonstrated that Mn induced the ER stress via
      activation of PERK and IRE1 signaling pathway, which contributed to the
      occurrence of apoptosis in cultured slices. 

PMID- 23948122
TI  - Incidence of shoulder injuries after generalized tonic-clonic seizure admitted to
      intensive care.

PMID- 23948123
TI  - What happens to serum metal ion levels after a metal-on-metal bearing is removed?
AB  - Serum cobalt (Co) and chromium (Cr) levels are commonly used to screen for
      excessive wear of metal-on-metal hip replacements. However, it is unknown how
      rapidly these should decline after revision. 25 patients with average Co and Cr
      ion levels of 56.3 MUg/L and 20.5 MUg/L were followed with serial ion level
      testing post-revision. Over the first 6 weeks post-revision, the rate of decline
      for Co and Cr was approximately 2% per day and this slowed to approximately 1%
      decline per day over the ensuing 6 weeks. This translated to a decline of
      approximately 80% from the starting value after 6 weeks and a decline of
      approximately 90% after 12 weeks post-revision. The rate of decline for both Co
      and Cr was significantly faster during the first 6 weeks (P<0.001). In patients
      with ultra-high Cr levels>20 MUg/L, the rate of Cr decline is less predictable
      and may be protracted leading to persistent elevation above 5 MUg/L for one year
      or more post-revision in some cases.

PMID- 23948124
TI  - Laser scanning as a useful tool in implant retrieval analysis: a demonstration
      using rotating platform and fixed bearing tibial inserts.
AB  - Objective methods for analyzing arthroplasty retrieval implants are needed. To
      address this, we used a readily available laser scanner to analyze damage
      deviations between cohorts of rotating platform and fixed bearing inserts
      previously analyzed using traditional, subjective retrieval analysis methods. We
      asked the following research questions: 1) Do articular surface deviations
      measured by the scanner correlate with the subjective damage scores? 2) Do
      articular surface deviations differ between inserts due to design differences?
      Correlations between deviations and damage scores were present in RP but not FB
      inserts. Seven different deviation patterns were present between the RP and FB
      inserts and were a function of design. In conclusion laser scanning was found to
      be a useful objective tool for analyzing arthroplasty retrievals. 

PMID- 23948125
TI  - Linagliptin for patients aged 70 years or older with type 2 diabetes inadequately
      controlled with common antidiabetes treatments: a randomised, double-blind,
      placebo-controlled trial.
AB  - BACKGROUND: A substantial proportion of patients with type 2 diabetes are elderly
      (>=65 years) but this group has been largely excluded from clinical studies of
      glucose-lowering drugs. We aimed to assess the effectiveness of linagliptin, a
      dipeptidyl peptidase-4 inhibitor, in elderly patients with type 2 diabetes.
      METHODS: In this randomised, double-blind, parallel-group, multinational phase 3
      study, patients aged 70 years or older with type 2 diabetes, glycated haemoglobin
      A1c (HbA1c) of 7.0% or more, receiving metformin, sulfonylureas, or basal
      insulin, or combinations of these drugs, were randomised (by computer-generated
      randomisation sequence, concealed with a voice-response system, stratified by
      HbA1c level [<8.5% vs >=8.5%] and insulin use [yes vs no], block size four) in a
      2:1 ratio to once-daily oral treatment with linagliptin 5 mg or matching placebo
      for 24 weeks. Investigators and participants were masked to assignment throughout
      the study. The primary endpoint was change in HbA1c from baseline to week 24.
      This trial is registered with ClinicalTrials.gov, number NCT01084005. FINDINGS:
      241 community-living outpatients were randomised (162 linagliptin, 79 placebo).
      Mean age was 74.9 years (SD 4.3). Mean HbA1c was 7.8% (SD 0.8). At week 24,
      placebo-adjusted mean change in HbA1c with linagliptin was -0.64% (95% CI -0.81
      to -0.48, p<0.0001). Overall safety and tolerability were much the same between
      the linagliptin and placebo groups; 75.9% of patients in both groups had an
      adverse event (linagliptin n=123, placebo n=60). No deaths occurred. Serious
      adverse events occurred in 8.6% (14) of patients in the linagliptin group and
      6.3% (five) patients in the placebo group; none were deemed related to study
      drug. Hypoglycaemia was the most common adverse event in both groups, but did not
      differ between groups (24.1% [39] in the linagliptin group, 16.5% [13] in the
      placebo group; odds ratio 1.58, 95% CI 0.78-3.78, p=0.2083). INTERPRETATION: In
      elderly patients with type 2 diabetes linagliptin was efficacious in lowering
      glucose with a safety profile similar to placebo. These findings could inform
      treatment decisions for achieving individualised glycaemic goals with minimal
      risk in this important population of patients. FUNDING: Boehringer Ingelheim.

PMID- 23948126
TI  - Frailty and diabetes.

PMID- 23948127
TI  - Food selectivity in children with and without an autism spectrum disorder:
      investigation of diagnosis and age.
AB  - Feeding problems are common in children with autism spectrum disorders (ASDs),
      with food selectivity being the most frequently reported. Selectivity based on
      type and/or texture of food is of concern in those with ASD. Variations in
      symptom presentation of food selectivity in children with different autism
      spectrum diagnoses across childhood have not often been investigated. Parent
      report of food selectivity was examined in 525 children age 2-18 years diagnosed
      with autistic disorder, PDD-NOS, Asperger's disorder, atypical development, and
      typical development using information garnered from the Autism Spectrum Disorder
      Comorbidity for Children (ASD-CC), a tool to assess emotional issues and comorbid
      psychopathology. Individuals with an ASD were reported to have significantly more
      food selectivity than both the atypically developing group and the typically
      developing group. In addition, the ASD groups, when looked at together, showed a
      decrease in food selectivity across childhood with significant decrease in the
      Asperger's disorder group. 

PMID- 23948128
TI  - Calf circumference, frailty and physical performance among older adults living in
      the community.
AB  - BACKGROUND & AIMS: Lean body mass loss has been indicated as a reliable marker of
      frailty and poor physical performance among older individuals. We evaluated the
      relationship between calf circumference and frailty, physical performance, muscle
      strength, and functional status in persons aged 80 years or older. METHODS: Data
      are from the baseline evaluation of the Aging and Longevity Study in the Sirente
      geographic area (ilSIRENTE Study) (n = 357). The calf circumference was measured
      at the point of greatest circumference. Frailty was categorized according to the
      present of slow gait speed, weakness, weight loss, energy expenditure and
      exhaustion. Physical performance was assessed using the physical performance
      battery score, which is based on three timed tests: 4-m walking speed test, the
      balance test and the chair stand test. Analyses of covariance were performed to
      evaluate the relationship between different calf circumference and physical
      function. RESULTS: After adjustment for potential confounders, which included
      age, gender, education, body mass index, sensory impairments, cerebrovascular
      diseases, albumin, reactive C protein, interleukine-6, and cholesterol, physical
      performance (SPPB score: 7.27 versus 6.18, p = 0.02) and muscle strength (Hand
      Grip: 32 kg versus 28 kg, p = 0.03) measures significantly improved as calf
      circumference increased. The frailty index score was significantly lower among
      subjects with higher calf circumference (1.66 versus 2.17, p = 0.01).
      CONCLUSIONS: The present study suggests that among community-dwelling older
      people, calf circumference may be positively related to lower frailty index and
      higher functional performance. As such, calf circumference is a valuable tool for
      guiding public health policy and clinical decisions.

PMID- 23948129
TI  - Reply to comments on the paper "Spectroscopic and computational study of the
      major oxidation products formed during the reaction of two quercetin conformers
      with a free radical ", made by Monica Scognamiglio, Fabio Temussi, Brigida
      D'Abrosca, and Antonio Fiorentino.

PMID- 23948130
TI  - Working in concert: the metalloaminopeptidases from Plasmodium falciparum.
AB  - Malaria remains the world's most prevalent human parasitic disease. Because of
      the rapid spread of drug resistance in parasites, there is an urgent need to
      identify diverse new drug targets. One group of proteases that are emerging as
      targets for novel antimalarials are the metalloaminopeptidases. These enzymes
      catalyze the removal of the N-terminal amino acids from proteins and peptides.
      Given the restricted specificities of each of these enzymes for different N
      terminal amino acids, it is thought that they act in concert to facilitate
      protein turnover. Here we review recent structure and functional data relating to
      the development of the Plasmodium falciparum metalloaminopeptidases as drug
      targets. 

PMID- 23948131
TI  - Changes in illness-related cognitions rather than distress mediate improvements
      in irritable bowel syndrome (IBS) symptoms and disability following a brief
      cognitive behavioural therapy intervention.
AB  - OBJECTIVE: A previous randomised controlled trial demonstrated that a cognitive
      behavioural therapy (CBT) self-management intervention significantly improved
      irritable bowel syndrome (IBS) symptoms and disability compared to treatment as
      usual (TAU). The current study analysed additional data to establish whether; 1)
      cognitive, behavioural and emotional factors hypothesized to perpetuate IBS
      symptoms and disability changed following CBT and, 2) ascertain if changes in
      these factors over the intervention period mediated treatment effects 6-months
      later. METHOD: IBS patients (CBT = 31, TAU = 33) completed measures pre-and-post
      intervention including: Brief Illness Perception Questionnaire, Hospital Anxiety
      & Depression Scale and Cognitive and Behavioural Responses to Symptoms
      Questionnaire. Path models were evaluated to determine whether changes in
      cognitive and behavioural factors over the treatment period mediated treatment
      effects. RESULTS: Compared to TAU, CBT patients showed significant positive
      changes on several cognitive variables but not anxiety and depression following
      intervention. Positive change in illness perceptions following intervention
      mediated the treatment effect on improved IBS symptom severity and social
      adjustment six months later. Changes in damaging beliefs mediated the effect on
      social adjustment. CONCLUSIONS: Change in cognition rather than mood mediated
      treatment related improvements. Changing negative perceptions of IBS appears to
      be a particularly important treatment mechanism.

PMID- 23948132
TI  - Brazilein, a compound isolated from Caesalpinia sappan Linn., induced growth
      inhibition in breast cancer cells via involvement of GSK-3beta/beta
      Catenin/cyclin D1 pathway.
AB  - Caesalpinia sappan Linn. has long been used in traditional medicine in China.
      Here, the anticancer activity of brazilein, a compound isolated from C. sappan
      Linn. was investigated. MTT assay showed that the IC50 value of brazilein against
      human breast cancer MCF-7 cells was 7.23 +/- 0.24 MUmol/L. PI staining and flow
      cytometry analysis indicated that brazilein caused cell cycle arrest in G1 phase.
      Western blot and RT-PCR assay demonstrated that cyclin D1, a key factor of the G1
      to S phase progression, was downregulated in a concentration-dependent manner by
      brazilein treatment. Further Western blot and RNA interference assay showed that
      brazilein treatment activated GSK-3beta and following reduced beta-Catenin
      protein, which accounted for the downregulation of cyclin D1 and blockage of cell
      cycle at G1 phase. Together, all these results illustrated that brazilein induced
      growth inhibition of breast cancer cells and downregulation of GSK-3beta/beta
      Catenin pathway was involved in its action mechanism.

PMID- 23948133
TI  - Risk of severe dysglycemia among diabetic patients receiving levofloxacin,
      ciprofloxacin, or moxifloxacin in Taiwan.
AB  - BACKGROUND: Observational studies and fatal case reports raise concern about the
      safety of severe dysglycemia associated with fluoroquinolone use. The objective
      of this study was to assess the risk of severe dysglycemia among diabetic
      patients who received different fluoroquinolones. METHODS: In a population-based
      inception cohort study of diabetic patients covering the period from January 2006
      to November 2007, outpatient new users of levofloxacin, ciprofloxacin,
      moxifloxacin, cephalosporins, and macrolides orally were identified. Study events
      were defined as emergency department visits or hospitalization for dysglycemia
      within 30 days following the initiation of antibiotic therapy. Results were
      analyzed with adjusted multinomial propensity score. RESULTS: A total of 78 433
      diabetic patients receiving the antibiotics of interest were included in the
      study. The absolute risk of hyperglycemia per 1000 persons was 6.9 for
      moxifloxacin and 1.6 for macrolides. In contrast, the risk of hypoglycemia was
      10.0 for moxifloxacin and 3.7 for macrolides. The adjusted odds ratios (AORs) and
      95% confidence intervals (CIs) of levofloxacin, ciprofloxacin, and moxifloxacin
      compared with macrolides were 1.75 (1.12-2.73), 1.87 (1.20-2.93), and 2.48 (1.50
      4.12), respectively, for hyperglycemia and 1.79 (1.33-2.42), 1.46 (1.07-2.00),
      and 2.13 (1.44-3.14), respectively, for hypoglycemia. Patients taking
      moxifloxacin faced a significantly higher risk of hypoglycemia than those
      receiving ciprofloxacin. A significant increase in the risk of hypoglycemia was
      also observed among patients receiving moxifloxacin concomitantly with insulin
      (AOR, 2.28; 95% CI, 1.22-4.24). CONCLUSIONS: Diabetics using oral
      fluoroquinolones faced greater risk of severe dysglycemia. The risk of
      hypoglycemia varied according to the type of fluoroquinolone administered, and
      was most commonly associated with moxifloxacin.

PMID- 23948134
TI  - Characterization of Treponema spp. isolates from pigs with ear necrosis and
      shoulder ulcers.
AB  - Ear necrosis and shoulder ulcers in pigs are animal welfare problems and ethical
      issues that can cause economic losses for producers. Spirochetes have been
      observed microscopically in scrapings from pig ulcers since the early 1900s, but
      have until recently not been cultured and therefore not characterized. In this
      study, 12 Treponema spp. isolates were acquired from porcine ear necrosis,
      shoulder ulcers and gingiva. DNA analysis of the 16S rRNA-tRNA(Ile) intergenic
      spacer region (ISR2) or the 16S rRNA gene revealed relatedness to oral treponemes
      found in dogs and humans. All isolates except one aligned into two clusters,
      Treponema pedis and Treponema sp. OMZ 840-like. The 16S rRNA gene of the
      remaining isolate shared 99% nucleotide identity with Treponema parvum. Genetic
      fingerprinting of the isolates was performed through random amplification of
      polymorphic DNA (RAPD). In addition, the isolates were characterized by
      biochemical tests, including api((r))ZYM, tryptophanase and hippuricase activity,
      and by testing the antimicrobial susceptibility to tiamulin, valnemulin, tylosin,
      tylvalosin, lincomycin and doxycycline using broth dilution. All isolates except
      two showed unique RAPD fingerprints, whereas metabolic activity tests could not
      differentiate between the isolates. The MICs of all antimicrobial agents tested
      were low. 

PMID- 23948135
TI  - Poly(ethyleneimines) in dermal applications: biocompatibility and antimicrobial
      effects.
AB  - Cationic polyamines, such as poly(ethyleneimines) (PEIs), may recommend
      themselves for antimicrobial applications as they can interact with microbial
      membranes resulting in their disruption. The purpose of the study was the
      assessment of biocompatibility and antibacterial activity of PEIs with different
      architectures (branched (b) and linear (l)) and molar masses (0.8-750 kDa). lPEI
      and bPEI exhibited a strong antibacterial activity against Staphylococcus aureus
      and Escherichia coli with a more pronounced effect on the Gram-positive bacteria.
      lPEIs further demonstrated a higher antibacterial efficacy compared to bPEIs but
      no significant differences between 5 and 25 kDa were observed. In accordance,
      antibacterial activity of bPEI did not specifically depend on molar mass. Only
      slightly lower minimal inhibitory concentrations (MIC) were observed at 5 kDa (S.
      aureus) and 25 kDa (E. coli) in the tests. As PEIs are compelling candidates for
      use in antimicrobial treatment, two basic aspects have to be investigated:
      treatment effectiveness and safety. PEIs clearly induced molecular weight
      dependent cytotoxic effects in vitro. PEIs with low molecular weight (0.8 and 5
      kDa) exhibited higher biocompatibility. Nonetheless, the results confirmed a low
      genotoxic potential of lPEI and bPEIs. In conclusion, 2.5 kDa-lPEI and 0.8 kDa
      bPEI can be recommended for use as antimicrobial polymers in dermal applications
      due to their high biocompatibility with concomitant antibacterial efficacy.

PMID- 23948136
TI  - Multilayered structure based on poly(N,N-dimethyl-acrylamide-co-3,9-divinyl
      2,4,8,10-tetraoxaspiro (5.5) undecane) prepared in a multiphase gelation process.
AB  - The study is devoted to the preparation of a multi-membrane gel system based on
      poly(N,N-dimethyl-acrylamide-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5)
      undecane) copolymer. The complex supra-structure was realized by layer by layer
      deposition technique, from the gel-core to the periphery by crosslinking poly(N,N
      dimethyl-acrylamide-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5) undecane) (P(DMA
      co-U)) with N,N'-methylene-bis-acrylamide and using as well beta-cyclodextrin
      with double purpose as compound for constructing further the edge of the
      interfacial supramolecular assemblies and to improve the host-guest complexation
      of further bioactive compounds. Basic copolymer has dual thermo- and pH sensitive
      character. The multi-membrane 'onion-like' gel system was tested as matrix for
      embedding Norfloxacin. Hematologic, biochemical, immunologic studies used to
      determine the biocompatibility of multi-membrane gel structures loaded with drug
      that directly contact living tissue provided a reasonable assessment of safety as
      implants. Histopathologic exams did not reveal any disturbances of the normal
      liver architecture in animals with multi-membrane gel system containing
      Norfloxacin compared to control group with sterile cotton pellets implant. Good
      biocompatibility for the implants based on multi-membrane gel structures loaded
      with drug were achieved from the in vivo tests these suggesting that biomaterials
      may be suitable for in vivo use as a local drug delivery system.

PMID- 23948137
TI  - Bulk, surface properties and water uptake mechanisms of salt/acid amorphous
      composite systems.
AB  - Developing amorphous pharmaceuticals can be desirable due to advantageous
      biopharmaceutical properties. Low glass transition temperature (Tg) amorphous
      drugs can be protected from crystallisation by mixing with high Tg excipients,
      such as polymers, or with salt forms. However, both polymers and salts can
      enhance the water uptake. The aim of this study was to formulate physico
      chemically stable amorphous materials, by co-processing different proportions of
      sulfathiazole and its sodium salt to produce an optimum ratio, characterised by
      the best physical stability and lowest hygroscopicity. Both sulfathiazole and
      salt amorphised upon spray drying. At room temperature, sulfathiazole
      crystallised within 1h at <5% relative humidity while the salt deliquesced when
      exposed to ambient humidity conditions. In the case of composite systems, FTIR
      spectroscopy, thermal and surface analysis suggested interactions with an
      acid:salt stoichiometry of 1:2. Increasing proportions of salt raised the Tg,
      enhancing the storage stability, however this was opposed by an enhanced
      hygroscopicity. The water uptake mechanism within the different amorphous
      systems, analysed by fitting the water sorption isotherms with the Young and
      Nelson equation, was dependent on the ratio employed, with the salt and the acid
      facilitating absorption and adsorption, respectively. Tuning the properties of
      amorphous salt/acid composites by optimising the ratio appears potentially
      promising to improve the physical stability of amorphous formulations. 

PMID- 23948138
TI  - Articulating biological and cultural evolution: comment on "Surname distribution
      in population genetics and in statistical physics" by Paolo Rossi.

PMID- 23948139
TI  - The impact of pulsed electric fields on cells and biomolecules: comment on
      "Lightning-triggered electroporation and electrofusion as possible contributors
      to natural horizontal gene transfer" by Tadej Kotnik.

PMID- 23948140
TI  - Surname statistics--crossing the boundary between disciplines: comment on
      "Surname distribution in population genetics and in statistical physics" by Paolo
      Rossi.

PMID- 23948141
TI  - What can we do with surnames today? An anthropologist point of view: comment on
      "Surname distribution in population genetics and in statistical physics" by Paolo
      Rossi.

PMID- 23948142
TI  - What's in a name?: Comment on "Surname distribution in population genetics and in
      statistical physics".

PMID- 23948143
TI  - Toward the practical implementation of eye-related bioavailability prediction
      models.
AB  - The development and registration of reformulated ophthalmic products (OPs)
      requires eye-related bioavailability (BA) assessments. Common BA algorithms
      associated with other routes of application, such as the oral route, cannot be
      easily applied to eye-related BA testing. Here, we provide an analysis of the
      current literature and suggestions for further directions in the development of
      high-capacity, cost-effective, and highly predictive nonclinical models of eye
      related drug BA. One, or a combination of these models, has the potential for
      routine use in research laboratories and/or the pharmaceutical industry to
      overcome various obstacles in reformulated OP development and registration. 

PMID- 23948144
TI  - Risk-based methods for fish and terrestrial animal disease surveillance.
AB  - Over recent years there have been considerable methodological developments in the
      field of animal disease surveillance. The principles of risk analysis were
      conceptually applied to surveillance in order to further develop approaches and
      tools (scenario tree modelling) to design risk-based surveillance (RBS)
      programmes. In the terrestrial animal context, examples of risk-based
      surveillance have demonstrated the substantial potential for cost saving, and a
      similar benefit is expected also for aquatic animals. RBS approaches are
      currently largely absent for aquatic animal diseases. A major constraint in
      developing RBS designs in the aquatic context is the lack of published data to
      assist in the design of RBS: this applies to data on (i) the relative risk of
      farm sites becoming infected due to the presence or absence of a given risk
      factor; (ii) the sensitivity of diagnostic tests (specificity is often addressed
      by follow-up investigation and re-testing and therefore less of a concern); (iii)
      data on the variability of prevalence of infection for fish within a holding
      unit, between holding units and at farm level. Another constraint is that some of
      the most basic data for planning surveillance are missing, e.g. data on farm
      location and animal movements. In Europe, registration or authorisation of fish
      farms has only recently become a requirement under EU Directive 2006/88.
      Additionally, the definition of the epidemiological unit (at site or area level)
      in the context of aquaculture is a challenge due to the often high level of
      connectedness (mainly via water) of aquaculture facilities with the aquatic
      environment. This paper provides a review of the principles, methods and examples
      of RBS in terrestrial, farmed and wild animals. It discusses the special
      challenges associated with surveillance for aquatic animal diseases (e.g.
      accessibility of animals for inspection and sampling, complexity of rearing
      systems) and provides an overview of current developments relevant for the design
      of RBS for fish diseases. Suggestions are provided on how the current constraints
      to applying RBS to fish diseases can be overcome. 

PMID- 23948145
TI  - Nordic veterinarians' threshold for medical treatment of dairy cows, influence on
      disease recording and medicine use: mild clinical mastitis as an example.
AB  - National databases for dairy cows in the four Nordic countries, Denmark, Finland,
      Norway and Sweden, have been found to capture varying proportions of disease
      events on farm. A variation in the thresholds of veterinarians to initiate
      medical treatment may be a reason for this. Studying these thresholds may
      increase the understanding of prudent use of antibiotics. The primary objective
      of this study was to investigate whether Nordic veterinarians, on a between
      country-level, vary in their intention to start medical treatment of a dairy cow
      with mild clinical mastitis, on the same day as making the diagnosis. The
      threshold for initiating treatment was quantified as an intention score.
      Secondary, underlying behavioural components of the intention score was studied
      within each country. A social psychology model, the Theory of Planned Behaviour
      (TPB), was used to design a questionnaire that was distributed to 1047
      veterinarians in cattle practice in the four countries during autumn 2010. The
      response rate was around 50% in all the countries, and 543 observations were
      retained for analysis. The between-country differences in intention were tested
      with one-way analysis of variance. Multivariable linear regression was used to
      estimate the proportion of variability in intention explained by the three
      behavioural components, attitude, subjective norm and perceived behavioural
      control. The Spearman rank correlations between specific beliefs about the
      behaviour and intention scores were estimated to find beliefs of high influence
      on the decision to treat or not. Intention scores differed between all countries
      (p<0.05) except between NO and SE (p=0.06). The mean intention scores were 0.71,
      0.42, 0.58 and 0.50 in DK, FI, NO and SE, respectively. As measured by the
      adjusted R(2) in linear regression models, the underlying behavioural components
      of the TPB explained 0.37, 0.41, 0.40 and 0.48 of the variation in intention
      scores in DK, FI, NO and SE, respectively. Attitude was the most important
      predictor in DK, NO and SE, but perceived behavioural control was most important
      in FI. In all countries the specific attitude belief of highest influence was
      that starting treatment the same day as diagnosing a case of mild clinical
      mastitis gives the best result, compared to delaying treatment. The varying
      intentions of veterinarians to initiate medical treatment are likely to influence
      centrally registered mastitis incidence. This study has given an improved
      understanding of this behaviour, which may be useful in intervention studies or
      campaigns aiming at prudent use of antibiotics on dairy farms. 

PMID- 23948146
TI  - Sagittal abdominal diameter may effectively predict future complications and
      increased mortality in intensive care unit patients with severe sepsis.
AB  - PURPOSE: To investigate whether increased visceral adipose tissue is a risk
      factor for increased morbidity and mortality in intensive care patients with
      severe sepsis. MATERIALS AND METHODS: In this prospective cohort study, body mass
      index (BMI) and sagittal abdominal diameter (SAD) were measured in all patients
      with severe sepsis immediately after admission in the intensive care unit (ICU).
      The patients were followed up until death or discharge from ICU. The study's
      primary outcome measure was mortality until day 60 after admission, while
      secondary outcomes were morbidity, length of stay, and length of ventilation in
      ICU. RESULTS: Of the 30 patients, 24 (80%) developed septic shock, 6 (20%)
      multiple organ dysfunction syndrome, 13 (43.3%) necessitated continuous
      venovenous hemodiafiltration, while 6 (20%) of them died. BMI and SAD had a
      statistically significant positive linear correlation with ICU length of stay (P
      < .001) and length of ventilation (P <= .001). However, only SAD was
      significantly correlated with the development of multiple organ dysfunction
      syndrome (P = .033), the need for continuous venovenous hemodiafiltration (P =
      .004), and death (P = .033). CONCLUSION: An increased SAD may effectively predict
      future complications and increased mortality in intensive care unit patients with
      severe sepsis.

PMID- 23948147
TI  - Cell-mediated immune responses in the head-associated lymphoid tissues induced to
      a live attenuated avian coronavirus vaccine.
AB  - Humoral immunity is important for controlling viral diseases of poultry, but
      recent studies have indicated that cytotoxic T cells also play an important role
      in the immune response to infectious bronchitis virus (IBV). To better understand
      the cell mediated immune responses to IBV in the mucosal and systemic immune
      compartments chickens were ocularly vaccinated with IBV. This induced a
      lymphocyte expansion in head-associated lymphoid tissues (HALT) and to a lesser
      extent in the spleen, followed by a rapid decline, probably due to homing of
      lymphocytes out of these organs and contraction of the lymphocyte population.
      This interpretation was supported by observations that changes in mononuclear
      cells were mirrored by that in CD3(+)CD44(+) T cell abundance, which presumably
      represent T effector cells. Increased interferon gamma (IFN-gamma) expression was
      observed in the mucosal immune compartment, i.e., HALT, after primary
      vaccination, but shifted to the systemic immune compartment after boosting. In
      contrast, the expression of cytotoxicity-associated genes, i.e., granzyme A
      (GZMA) and perforin mRNA, remained associated with the HALT after boosting. Thus,
      an Ark-type IBV ocular vaccine induces a central memory IFN-gamma response in the
      spleen while the cytotoxic effector memory response, as measured by GZMA and
      perforin mRNA expression, remains associated with CALT after boosting. 

PMID- 23948148
TI  - Immunomodulatory effects of the aromatic geranyl derivative filifolinone tested
      by the induction of cytokine expression.
AB  - Fish farming crops are constantly exposed to infectious diseases due to intensive
      production conditions under which microorganisms develop and spread easily,
      resulting in severe economic losses. The massive use of antibiotics to control
      these diseases has lead to the accumulation of residues and the development of
      drug resistance. Consequently, it is urgent to develop new pharmacological tools
      to stimulate protective immune responses in salmonids to combat infectious
      diseases. We evaluated the immunostimulant activity of terpenoid derivatives
      isolated from species of the Heliotropium genus, which had previously shown
      antiviral activity in salmon. The immunomodulatory effects of the 3 H-spiro [1
      benzofuran-2,1'-ciclohexane] derivative called filifolinone, were studied in
      vitro using the SHK-1 cell line derived from leucocytes of salmon head kidney and
      in vivo in Atlantic salmon. For the evaluation, we studied the effect of this
      compound in the expression of various cytokines. The results showed that
      Filifolinone increases the levels of expression of pro-inflammatory and anti
      inflammatory cytokines. This suggests that Filifolinone is a potential
      alternative immunomodulator for veterinary purposes. 

PMID- 23948149
TI  - Effects of ocean warming and acidification on fertilization in the Antarctic
      echinoid Sterechinus neumayeri across a range of sperm concentrations.
AB  - The gametes of marine invertebrates are being spawned into an ocean that is
      simultaneously warming and decreasing in pH. Predicting the potential for
      interactive effects of these stressors on fertilization is difficult, especially
      for stenothermal polar invertebrates adapted to fertilization in cold, viscous
      water and, when decreased sperm availability may be an additional stressor. The
      impact of increased temperature (2-4  degrees C above ambient) and decreased pH
      (0.2-0.4 pH units below ambient) on fertilization in the Antarctic echinoid
      Sterechinus neumayeri across a range of sperm concentrations was investigated in
      cross-factorial experiments in context with near future ocean change projections.
      The high temperature treatment (+4  degrees C) was also used to assess thermal
      tolerance. Gametes from multiple males and females in replicate experiments were
      used to reflect the multiple spawner scenario in nature. For fertilization at low
      sperm density we tested three hypotheses, 1) increased temperature enhances
      fertilization success, 2) low pH reduces fertilization and, 3) due to the cold
      stenothermal physiology of S. neumayeri, temperature would be the more
      significant stressor. Temperature and sperm levels had a significant effect on
      fertilization, but decreased pH did not affect fertilization. Warming enhanced
      fertilization at the lowest sperm concentration tested likely through stimulation
      of sperm motility and reduced water viscosity. Our results indicate that
      fertilization in S. neumayeri, even at low sperm levels potentially found in
      nature, is resilient to near-future ocean warming and acidification.

PMID- 23948150
TI  - Climate driven changes in subtidal kelp forest communities in NW Spain.
AB  - Reconstructions suggest a massive decline of nearly 1400 ha of kelp forest in
      North Western Spain in 2007. In line with global rising temperatures, we
      hypothesized that Sea Surface Temperature (SST) surpassed a lethal threshold for
      kelp. We examined whether changes in SST correlated to the proposed decline in
      kelp forest. All investigated SST characteristics suggested to affect kelp
      abundance increased significantly during the past thirty years, reaching extreme
      values during the last decade. In addition over the past two decades, the
      landscape formerly dominated by both cold and warm temperate canopy forming and
      understory species changed to one dominated by warm temperate understory species,
      resulting in a loss of vertical community structure. Fisheries landing data of
      kelp associated species was used to support the suggested change in kelp
      abundance. Subsequent recovery of the kelp appears to be occurring in deeper
      waters.

PMID- 23948151
TI  - [Prognostic value of the expression of vascular endothelial growth factor A and
      hypoxia-inducible factor 1alpha in patients undergoing surgery for non-small cell
      lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Studies suggest that hypoxia-inducible factor 1alpha
      (HIF-1alpha) expression favours expression of vascular endothelial growth factor
      A (VEGF-A) involving cellular proliferation, angiogenesis, and metastasis in
      different cancers including lung cancer. We investigated the correlation of HIF
      1alpha and VEGF-A with clinicopathologic parameters and clinical outcomes in
      surgically resected non-small cell lung cancer patients. PATIENTS AND METHOD:
      Prospective study to analyze the expression of VEGF-A and HIF-1alpha with real
      time-polymerase chain reaction in 66 patients operated on non-small cell lung
      cancer. RESULTS: Mean age was 62.7+/-9.8 and male:female ratio was 7.3:1.
      According to the new 2009 TNM classification, stage i, ii, and iii included 27
      (40.9%), 21 (31.8%) and 18 (27.3%) patients, respectively. Histological subtypes
      were: 47% squamous cell carcinoma, 33.3% adenocarcinoma, and 19.7% others. Mean
      follow-up time was 42.3 months. Median survival was 43.2 months and 5-year
      overall survival was 42.4%. There was no correlation between HIF-1alpha and VEGF
      A (P=.306). The overexpression of VEGF-A was found more frequent in advanced
      stage and in lymph nodes metastasis (P=.034 and P=.059, respectively). In
      multivariate analysis, T descriptor and VEGF-A overexpression were independent
      prognostic factors (odds ratio [OR]=2.37, P=.016, and OR=2.51, P=.008,
      respectively). HIF-1alpha overexpression showed an OR=0.540, but without
      statistical significance (P=.172). CONCLUSIONS: The present study revealed that
      VEGF-A overexpression was an adverse independent prognostic factor. On the
      contrary, HIF-1alpha overexpression showed a tendency to a protective effect on
      survival of surgically treated non-small cell lung cancer patients, although
      without statistical significance.

PMID- 23948152
TI  - Effect of architecture on the micellar properties of poly (E-caprolactone)
      containing sulfobetaines.
AB  - Linear and star-shape poly(E-caprolactone)-b-poly(N-(3-sulfopropyl)-N
      methacryloxyethyl-N,N-diethylammoniumbetaine) (L/sPCL-b-PDEAS) with 4 and 6 arms
      were synthesized with the combination of Ring Opening Polymerization (ROP) and
      Atom Transfer Radical Polymerization (ATRP). These copolymers self-assembled into
      micelles via solvent evaporation method. The critical micelle concentration
      (CMC), determined by fluorescence spectroscopy using pyrene as a probe, was lower
      than 10(-3)mg/mL and decreased with increasing arm numbers. Atom force microscopy
      (AFM) images showed that the micelles were spherical in shape with narrow size
      distribution. The hydrophobic drug model carotene was efficiently loaded in the
      polymeric micelles. The sizes and drug loading content (DLC) of the carotene
      loaded micelles increased with increasing drug content in feed. In vitro drug
      release experiment demonstrated that the release rate of carotene from the
      micelles was closely related to the arm numbers and drug loading content. Linear
      copolymer micelles showed the fastest release rate, 4-arm star shape copolymer
      micelles exhibited the lowest release rate. The micelles with higher drug loading
      content showed lower release rate. The release kinetics of carotene from micelles
      fitted the Ritger-Peppas equation. 

PMID- 23948153
TI  - Effects of various salts on structural polymorphism of reconstituted type I
      collagen fibrils.
AB  - Even though the behavior of collagen monomers self-assembling into fibrils is
      commonly understood in terms of hydrophobic and electrostatic interactions, the
      mechanisms that drive their ordered, longitudinal alignment to form a
      characteristic periodicity are still unclear. By introducing various salts into
      the collagen fibrillogenesis system, the intermolecular interactions of fibril
      formation were studied. We found that the pH and ion species play a critical role
      in forming native fibrils. Turbidity and electron microscopy revealed that
      collagen self-assembled into fibrils with a native banding pattern in the
      presence of multivalent ions. The isoelectric point of collagen in 12mM of NaCl
      is pH 8.9; it shifted to pH 9.4 and pH 7.0 after adding 10mM CaCl2 and Na2SO4,
      respectively. Native fibrils were reconstituted at pH 7.4 in salts with divalent
      anions and at pH 9.0 in salts with divalent cations. Circular dichroism
      spectroscopy showed a loss of helicity in the conditions where fibrillogenesis
      was unable to be achieved. The multivalent ions not only change the surface
      charge of collagen, but also facilitate the formation of fibrils with the native
      D-periodic banding pattern. It is likely that the binding multivalent ions induce
      the like-charge attraction and facilitate monomers' longitudinal registration to
      form fibrils with the native banding. 

PMID- 23948155
TI  - Transition from fetal to neonatal life: changes in cardiac function assessed by
      speckle-tracking echocardiography.
AB  - OBJECTIVE: Assessment of cardiac function by speckle-tracking (2D-S)
      echocardiography in the transitional period from fetal to neonatal life in a
      healthy population. METHODS: Ultrasound assessment of cardiac function of 30
      healthy fetuses at the gestational age of 28 weeks, and follow-up after birth
      using 2-D strain derived novel parameters such as longitudinal strain (S), strain
      rate (SR), tissue velocities, MPI- and E/E'-index, E/A- and E'/A'-rate of both
      right (RV) and left ventricles (LV) and interventricular septum (IVS) and
      comparison to conventionally measured cardiac stroke volume (SV), cardiac output
      (CO) and ejection fraction (EF). RESULTS: Ultrasound 2D-S performance and
      analysis were technically feasible and reproducible in all 30 fetuses and in the
      neonatal period. In fetuses, tissue velocities and SR measurements were
      homogenous for all regions of interest in both ventricles, and strain increased
      from apex to base and was significantly higher in the RV compared to LV. All
      calculated indices were almost identical for RV and LV. After birth, strain and
      strain rate exhibited significantly lower values, and systolic tissue velocities
      were higher in comparison to fetal values in both chambers and in all regions of
      interest. CONCLUSION: Speckle-tracking echocardiography is a feasible and
      reproducible technique in analyzing both fetal and newborn cardiac functions.
      Therefore, it might be useful in clinical routine examinations and give new
      insights in transitional physiology.

PMID- 23948154
TI  - The optimal combination of substrate chemistry with physiological fluid shear
      stress.
AB  - Osteoblasts on implanted biomaterials sense both substrate chemistry and
      mechanical stimulus. The effects of substrate chemistry alone and mechanical
      stimulus alone on osteoblasts have been widely studied. This study investigates
      the optimal combination of substrate chemistry and 12dyn/cm(2) physiological flow
      shear stress (FSS) by examining their influences on primary rat osteoblasts
      (ROBs), including the releases of ATP, nitric oxide (NO), and prostaglandin E2
      (PGE2). Self-assembled monolayers (SAMs) on glass slides with -OH, -CH3, and -NH2
      were employed to provide various substrate chemistries, whereas a parallel-plate
      fluid flow system produced the physiological FSS. Substrate chemistry alone
      exerted no observable effects on the releases of ATP, NO, and PGE2. Nevertheless,
      when ROBs were exposed to both substrate chemistry and FSS, the ATP releases of
      NH2 were upregulated about 12-fold compared to substrate chemistry alone, while
      the ATP releases of CH3 and OH was similarly increased 7-fold at the peak.
      Similar trends were observed for the releases of NO and PGE2. The expressions of
      ATP, NO, and PGE2 followed the pattern of NH2-FSS>Glass-FSS>CH3-FSS~OH-FSS. ROBs
      on NH2 produced the optimal combination of substrate chemistry with the
      physiological FSS. The F-actin organization and focal adhesion (FA) formation of
      ROBs on various SAMs without FSS were examined. NH2 produced the best results
      whereas CH3 and OH produced the worst ones. Inhibition of FAs and/or disruption
      of F-actin significantly decreased the releases of FSS-induced PGE2, NO, and/or
      ATP. Consequently, a mechanism was proposed that the best F-actin organization
      and FA formation of ROBs on NH2 lead to the optimal combination of substrate
      chemistry with the 12dyn/cm(2) physiological FSS. This mechanism gives guidance
      for the design of implanted biomaterials and bioreactors for bone tissue
      engineering. 

PMID- 23948156
TI  - Role of AIF-1 in the regulation of inflammatory activation and diverse disease
      processes.
AB  - Allograft Inflammatory Factor-1 (AIF-1) is a 17kDa cytoplasmic, calcium-binding,
      inflammation-responsive scaffold protein that is mainly expressed in immunocytes.
      AIF-1 influences the immune system at several key points and thus modulates
      inflammatory diseases. AIF-1 boosts the expression of inflammatory mediators such
      as cytokines, chemokines, inducible nitric oxide synthase (iNOS) and promotes
      inflammatory cell proliferation and migration. Here we provide an overview of the
      different pathological processes regulated by AIF-1 mainly including allograft
      rejection, autoimmune diseases, central nervous system (CNS) injury, vasculopathy
      and cancer et al. 

PMID- 23948157
TI  - Simultaneous detection of bee viruses by multiplex PCR.
AB  - Honey bee mortality is a serious problem that beekeepers in Argentina have had to
      face during the last 3 years. It is known that the consequence of the complex
      interactions between environmental and beekeeping parameters added to the effect
      of different disease agents such as viruses, bacteria, fungi and parasitic mites
      may result in a sudden collapse of the colony. In addition, multiple viral
      infections are detected frequently concomitantly in bee colonies. The aim of this
      study was to establish a multiplex polymerase chain reaction method for rapid and
      simultaneous detection of the most prevalent bee viruses. This multiplex PCR
      assay will provide specific, rapid and reliable results and allow for the cost
      effective detection of a particular virus as well as multiple virus infections in
      a single reaction tube. This method could be a helpful tool in the surveillance
      of the most frequently found bee viruses and to study the dynamics and the
      interactions of the virus populations within colonies. 

PMID- 23948158
TI  - Methods for detecting ATP hydrolysis and nucleic acid unwinding of Japanese
      encephalitis virus NS3 helicase.
AB  - Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic pathogen that is
      prevalent in south-east Asia. Because there is no specific antiviral agent, JEV
      still causes a high rate of neurologic sequelae and mortality in humans. The
      helicase encoded by the NS3 gene of JEV has emerged recently as a novel antiviral
      target for treatment. In this study, a soluble recombinant JEV helicase protein
      was expressed and purified. Methods for detecting the ATP hydrolysis and nucleic
      acid unwinding activity were developed by luminescence and fluorescence resonance
      energy transfer (FRET). The concentrations of enzyme, substrate, capture strand,
      ATP, and divalent ions were optimised in the ATPase and helicase reactions. The
      feasibility of using these two methods for high-throughput screening of NS3
      helicase inhibitors is discussed. 

PMID- 23948159
TI  - Update on the classification and treatment of localized scleroderma.
AB  - Morphea or localized scleroderma is a distinctive inflammatory disease that leads
      to sclerosis of the skin and subcutaneous tissues. It comprises a number of
      subtypes differentiated according to their clinical presentation and the
      structure of the skin and underlying tissues involved in the fibrotic process.
      However, classification is difficult because the boundaries between the different
      types of morphea are blurred and different entities frequently overlap. The main
      subtypes are plaque morphea, linear scleroderma, generalized morphea, and
      pansclerotic morphea. With certain exceptions, the disorder does not have serious
      systemic repercussions, but it can cause considerable morbidity. In the case of
      lesions affecting the head, neurological and ocular complications may occur.
      There is no really effective and universal treatment so it is important to make a
      correct assessment of the extent and severity of the disease before deciding on a
      treatment approach. 

PMID- 23948160
TI  - Afferent control of walking: are there distinct deficits associated to loss of
      fibres of different diameter?
AB  - OBJECTIVES: To compare the gait pattern in patients affected by different types
      of neuropathy. METHODS: We recruited healthy subjects (HS, n=38), patients with
      Charcot-Marie-Tooth disease type 1A (CMT1A) (n=10) and patients with diabetic
      neuropathy (DNP) (n=12). Neuropathy impairment score and neuropathy score were
      assessed. Body sway during quiet stance, and spatio-temporal gait parameters were
      recorded. RESULTS: Most patients had reduced or absent tendon-tap reflexes.
      Strength of foot dorsiflexor muscles (p<0.05) and conduction velocity (CV) of leg
      nerves (p<0.0001) were more impaired in CMT1A than DNP, whereas joint-position
      sense was more affected (p<0.05) in DNP. Body sway while standing was larger in
      DNP compared to CMT1A and HS (p<0.01 and p<0.0001 respectively). During gait, the
      distribution of foot sole contact pressure was abnormal in CMT1A (p<0.05) but not
      in DNP. Velocity and step length were decreased, and foot yaw angle at foot flat
      increased, in DNP with respect to CMT1A and HS (both variables, p<0.001). Gait
      velocity and step length were decreased (p<0.005) also in CMT1A, but to a smaller
      extent than in DNP, so that the difference between patient groups was significant
      (p<0.0005). Duration of the double support was protracted in DNP compared to
      CMT1A and HS (p<0.0005). For DNP only, velocity of gait and duration of single
      support were correlated (p<0.05) both to sway path and lower limb muscle
      strength. CONCLUSIONS: Changes in both body sway and stance phase of gait were
      larger in DNP than CMT1A, indicating more impaired static and dynamic control of
      balance when neuropathy affects the small in addition to the large afferent
      fibres. Diminished somatosensory input from the smaller fibres rather than muscle
      weakness or foot deformity plays a critical role in the modulation of the support
      phase of gait. SIGNIFICANCE: The analysis of balance and gait in patients with
      neuropathy can offer a tool for understanding the nature and functional impact of
      the neuropathy and should be included in their functional evaluation.

PMID- 23948161
TI  - Intimate partner violence in an outpatient palliative care setting.

PMID- 23948162
TI  - Multifunctional receptor-targeted nanocomplexes for the delivery of therapeutic
      nucleic acids to the brain.
AB  - Convection enhanced delivery (CED) is a method of direct injection to the brain
      that can achieve widespread dispersal of therapeutics, including gene therapies,
      from a single dose. Non-viral, nanocomplexes are of interest as vectors for gene
      therapy in the brain, but it is essential that administration should achieve
      maximal dispersal to minimise the number of injections required. We hypothesised
      that anionic nanocomplexes administered by CED should disperse more widely in rat
      brains than cationics of similar size, which bind electrostatically to cell
      surface anionic moieties such as proteoglycans, limiting their spread. Anionic,
      receptor-targeted nanocomplexes (RTN) containing a neurotensin-targeting peptide
      were prepared with plasmid DNA and compared with cationic RTNs for dispersal and
      transfection efficiency. Both RTNs were labelled with gadolinium for localisation
      in the brain by MRI and in brain sections by LA-ICP-MS, as well as with rhodamine
      fluorophore for detection by fluorescence microscopy. MRI distribution studies
      confirmed that the anionic RTNs dispersed more widely than cationic RTNs,
      particularly in the corpus callosum. Gene expression levels from anionic
      formulations were similar to those of cationic RTNs. Thus, anionic RTN
      formulations can achieve both widespread dispersal and effective gene expression
      in brains after administration of a single dose by CED. 

PMID- 23948163
TI  - Opposing influence of intracellular and membrane thiols on the toxicity of
      reducible polycations.
AB  - Toxicity of polycations has been recognized since their first use in gene
      delivery. Bioreducible polycations attract attention because of their improved
      safety due to selective intracellular degradation by glutathione (GSH). Here we
      present a systematic study of the toxicity of bioreducible poly(amido amine)s
      (PAA). PAA with increasing content of disulfide bonds were synthesized by Michael
      addition. Toxicity of PAA was evaluated in two cell lines with different innate
      levels of intracellular GSH. Increasing the content of disulfide bonds decreased
      the toxicity of PAA, with more significant decrease observed in cells with high
      GSH. Depleting intracellular GSH by diethyl maleate resulted in increased
      toxicity of bioreducible PAA. In contrast, increasing the GSH concentrations by
      growing cells in hypoxic conditions resulted in further decreased toxicity
      compared with cells grown in normoxic conditions. The presence of exofacial
      plasma membrane thiols selectively increased toxicity of bioreducible PAA while
      having no effect on non-degradable controls. These results improve our
      understanding of the cellular mechanisms of polycation toxicity. They also shed
      light on the opposing effects of different cellular thiol pools on the toxicity
      of bioreducible polycations. 

PMID- 23948164
TI  - Intracellular signaling mechanisms associated with CD47 modified surfaces.
AB  - We have previously established that recombinant CD47 can ameliorate the
      inflammatory response to synthetic polymeric surfaces. Here, we begin to profile,
      at the transcriptional, translational and cell signaling level, the inflammatory
      cell response when blood interacts with CD47 modified polyvinyl chloride (PVC)
      (CD47-PVC). We used qPCR arrays to compare transcriptional changes between human
      whole blood exposed to CD47-PVC or PVC. Transcription of IL1F5, IL1F10, IL17F,
      CCL3, CCL8, CCL28, CXCL12, and CXCL13 was upregulated in blood exposed to PVC,
      compared to CD47-PVC. The increase in CCL3 and CCL8 transcription correlated with
      an increase in the chemokines' presence in the plasma. Exposure of blood to CD47
      PVC resulted in an increase, compared to PVC, in transcription of CCL2, CCL4,
      CCL20, CXCL1, TGFbeta3, GDF3, GDF10, CD40LG, and TNFSF10. CD47-PVC exposure
      resulted in an increase of the following matrix metalloproteinase related genes:
      MMP1, MMP7, MMP13, and MMP16. Phosflow cytometry, and assays examining
      transcription factor binding, cell attachment, and genome-wide chromatin
      association indicated that members of the JAK-STAT signaling pathway,
      particularly JAK2 and STAT5, mediate inflammatory cell interactions with CD47
      PVC. Our data demonstrate that differential molecular responses to CD47 involve
      downregulation of cytokines, upregulation of MMPs, and JAK/STAT signaling
      mechanisms. 

PMID- 23948165
TI  - Design of a multiple drug delivery system directed at periodontitis.
AB  - Periodontal disease is highly prevalent, with 90% of the world population
      affected by either periodontitis or its preceding condition, gingivitis. These
      conditions are caused by bacterial biofilms on teeth, which stimulate a chronic
      inflammatory response that leads to loss of alveolar bone and, ultimately, the
      tooth. Current treatment methods for periodontitis address specific parts of the
      disease, with no individual treatment serving as a complete therapy. The present
      research sought to demonstrate development of a multiple drug delivery system for
      stepwise treatment of different stages of periodontal disease. More specifically,
      multilayered films were fabricated from an association polymer comprising
      cellulose acetate phthalate and Pluronic F-127 to achieve sequential release of
      drugs. The four types of drugs used were metronidazole, ketoprofen, doxycycline,
      and simvastatin to eliminate infection, inhibit inflammation, prevent tissue
      destruction, and aid bone regeneration, respectively. Different erosion times and
      adjustable sequential release profiles were achieved by modifying the number of
      layers or by inclusion of a slower-eroding polymer layer. Analysis of antibiotic
      and anti-inflammatory bioactivity showed that drugs released from the devices
      retained 100% bioactivity. The multilayered CAPP delivery system offers a
      versatile approach for releasing different drugs based on the pathogenesis of
      periodontitis and other conditions. 

PMID- 23948166
TI  - Accelerated fatigue of dentin with exposure to lactic acid.
AB  - Composite restorations accumulate more biofilm than other dental materials. This
      increases the likelihood for the hard tissues supporting a restoration (i.e.
      dentin and enamel) to be exposed to acidic conditions beyond that resulting from
      dietary variations. In this investigation the fatigue strength and fatigue crack
      growth resistance of human coronal dentin were characterized within a lactic acid
      solution (with pH = 5) and compared to that of controls evaluated in neutral
      conditions (pH = 7). A comparison of the fatigue life distributions showed that
      the lactic acid exposure resulted in a significant reduction in the fatigue
      strength (p <= 0.001), and nearly 30% reduction in the apparent endurance limit
      (from 44 MPa to 32 MPa). The reduction in pH also caused a significant decrease
      (p <= 0.05) in the threshold stress intensity range required for the initiation
      of cyclic crack growth, and significant increase in the incremental rate of crack
      extension. Exposure of tooth structure to lactic acid may cause demineralization,
      but it also increases the likelihood of restored tooth failures via fatigue, and
      after short time periods. 

PMID- 23948167
TI  - Controlled release of cisplatin from pH-thermal dual responsive nanogels.
AB  - In this study, a pH-thermal dual responsive nanogel was applied for cisplatin
      (CDDP) delivery. CDDP was loaded into the nanogels via conjugation with the
      carboxyl groups in the nanogels. The conjugation was confirmed by FTIR and XPS.
      The bonding between CDDP and COOH can be broken by the H(+) or Cl(-). We found
      that the CDDP released much faster at more acidic environment. The Cl(-)
      concentration in the human body is about 95-105 mm. The conjugated bond could be
      easily attacked by Cl(-) while the nanosystem is injected into the body. In order
      to diminish the Cl(-) triggering release of CDDP from the nanogels, we introduced
      a thermal-responsive units-NIPAm into the nanogel structure. After NIPAm
      introduced, the CDDP released much slower from the nanogels at 37  degrees C in
      pH = 7.38 buffer in the present of Cl(-) (150 mm) than that without NIPAm. And
      the CDDP also released slower from the nanogels at 37  degrees C than at 25 
      degrees C. By in vitro release behavior studying, we found that CDDP release from
      the NIPAm containing nanogels can be accelerated by H(+) attacking and reduced by
      temperature arising. By cellular uptake observation, we found that the nanogels
      were mainly localized in the cytoplasm of the cancer cells. The CDDP-loaded
      nanogels exhibited longer circulation time in vivo while compared to free CDDP.
      And it has better anti-cancer performance than free CDDP in vivo therapy of
      breast cancer in mice model. Furthermore, some side effects of CDDP, such as
      renal toxicity, phlebitis, bone marrow suppression etc. have also been reduced by
      nanogels loading. The in vitro and in vivo results demonstrated that the dual
      responsible nanogel is a suitable CDDP delivery candidate. 

PMID- 23948168
TI  - The road map to integrated dementia prevention and care.

PMID- 23948169
TI  - The international consensus classification for hippocampal sclerosis: an
      important step towards accurate prognosis.

PMID- 23948170
TI  - Intracranial and extracranial arteries in migraine.

PMID- 23948171
TI  - Intracranial and extracranial arteries in migraine.

PMID- 23948172
TI  - Intracranial and extracranial arteries in migraine--authors' reply.

PMID- 23948173
TI  - Hypothermia in paediatric traumatic brain injury--authors' reply.

PMID- 23948174
TI  - Hypothermia in paediatric traumatic brain injury.

PMID- 23948175
TI  - Dolphins, dogs, and robot seals for the treatment of neurological disease.
AB  - A growing body of evidence suggests that animal-assisted therapies and activities
      involving all kinds of real and even robotic animals can have beneficial eff ects
      in people with neurological disease or mental illness. But what is the quality of
      that evidence and do these interventions really provide any health benefits?
      Adrian Burton investigates.

PMID- 23948176
TI  - Lifeline.

PMID- 23948177
TI  - Neurological complications of dengue virus infection.
AB  - Dengue is the second most common mosquito-borne disease affecting human beings.
      In 2009, WHO endorsed new guidelines that, for the first time, consider
      neurological manifestations in the clinical case classification for severe
      dengue. Dengue can manifest with a wide range of neurological features, which
      have been noted--depending on the clinical setting--in 0.5-21% of patients with
      dengue admitted to hospital. Furthermore, dengue was identified in 4-47% of
      admissions with encephalitis-like illness in endemic areas. Neurological
      complications can be categorised into dengue encephalopathy (eg, caused by
      hepatic failure or metabolic disorders), encephalitis (caused by direct virus
      invasion), neuromuscular complications (eg, Guillain-Barre syndrome or transient
      muscle dysfunctions), and neuro-ophthalmic involvement. However, overlap of these
      categories is possible. In endemic countries and after travel to these regions,
      dengue should be considered in patients presenting with fever and acute
      neurological manifestations.

PMID- 23948178
TI  - Tinnitus: causes and clinical management.
AB  - Tinnitus is the perception of sound in the absence of a corresponding external
      acoustic stimulus. With prevalence ranging from 10% to 15%, tinnitus is a common
      disorder. Many people habituate to the phantom sound, but tinnitus severely
      impairs quality of life of about 1-2% of all people. Tinnitus has traditionally
      been regarded as an otological disorder, but advances in neuroimaging methods and
      development of animal models have increasingly shifted the perspective towards
      its neuronal correlates. Increased neuronal firing rate, enhanced neuronal
      synchrony, and changes in the tonotopic organisation are recorded in central
      auditory pathways in reaction to deprived auditory input and represent--together
      with changes in non-auditory brain areas--the neuronal correlate of tinnitus.
      Assessment of patients includes a detailed case history, measurement of hearing
      function, quantification of tinnitus severity, and identification of causal
      factors, associated symptoms, and comorbidities. Most widely used treatments for
      tinnitus involve counselling, and best evidence is available for cognitive
      behavioural therapy. New pathophysiological insights have prompted the
      development of innovative brain-based treatment approaches to directly target the
      neuronal correlates of tinnitus.

PMID- 23948179
TI  - Therapeutic outcomes of combining cryotherapy, chemotherapy and DC-CIK
      immunotherapy in the treatment of metastatic non-small cell lung cancer.
AB  - Currently there are no effective therapies for the treatment of metastatic non
      small cell lung cancer (NSCLC). Here, we conducted a retrospective study of 161
      patients to evaluate the therapeutic effects of combining cryosurgery,
      chemotherapy and dendritic cell-activated cytokine-induced killer cells (DC-CIK)
      immunotherapy. The overall survival (OS) after diagnosis of metastatic NSCLC to
      patient death was assessed during a 5-years follow-up period. OS of patients who
      received comprehensive cryotherapy was (median OS, 20 months; n = 86)
      significantly longer than that of patients who did not received cryotherapy
      (median OS, 10 months; n = 75; P < 0.0001). Five treatment combinations were
      selected: chemotherapy (n = 44); chemo-immunotherapy (n = 31); cryo-chemotherapy
      (n = 32); cryo-immunotherapy (n = 21); and cryo-chemo-immunotherapy (n = 33). A
      combination of cryotherapy with either chemotherapy or immunotherapy lead to
      significantly longer OS (18 months and 17 months, respectively) compared to
      chemotherapy and chemo-immunotherapy (8.5 months and 12 months, respectively; P <
      0.001); however, the median OS of patients who underwent cryo-chemo-immunotherapy
      was significantly longer (27 months) compared to the other treatment programs (P
      < 0.001). In conclusion, a combination of cryotherapy, chemotherapy and DC-CIK
      immunotherapy proved the best treatment option for metastatic NSCLC in this group
      of patients.

PMID- 23948180
TI  - Aging-related endothelial dysfunction in the aorta from female senescence
      accelerated mice is associated with decreased nitric oxide synthase expression.
AB  - The present study investigated the time-course for aging-associated effects on
      contractile and relaxing vascular responses and nitric oxide (NO) production in
      the aorta from female senescence-accelerated resistant (SAMR1) and prone (SAMP8)
      mice. Both SAMR1 and SAMP8 were studied at three different ages: 3 (young), 6
      (middle age) and 10 (old) months. Concentration-response curves to phenylephrine
      (10(-8) to 10(-5) M) or acetylcholine (10(-9) to 10(-5) M) were performed in the
      aortic rings in the absence or in the presence of NO synthase (NOS) inhibitor L
      NAME (10(-4) M). Protein and gene expression for endothelial NOS (eNOS) was
      determined by immunofluorescence, Western blot and real-time PCR. Although we
      have not seen any difference in vascular responses when comparing both strains at
      3 months old, we found a significant aging-associated impairment of vascular
      reactivity that follows a distinct time-course in SAMR1 and SAMP8. In SAMR1,
      increases in phenylephrine contraction and decreases in acetylcholine relaxation
      were only seen at 10 months old, while SAMP8 displays altered responses at 6
      months that are further impaired at 10 months old. L-NAME treatment enhanced
      phenylephrine contractions and completely inhibited acetylcholine relaxations in
      all age groups of SAMR1 and SAMP8. However, the magnitude of increase in
      phenylephrine contraction by L-NAME was markedly reduced by aging and followed a
      faster pace in SAMP8. Similar pattern of responses was observed in the time
      course for changes of eNOS expression, suggesting an earlier and more pronounced
      aging-associated decrease of NO production and eNOS expression in SAMP8. These
      results reveal that aging enhances contractile responses to phenylephrine and
      decreases endothelium-dependent relaxation to acetylcholine in the aorta from
      female mice by a mechanism that involves a decrease of NO production. This
      process occurs earlier in the aorta from SAMP8 mice, establishing these mice as
      suitable model to study cardiovascular aging in a convenient and standard time
      course.

PMID- 23948181
TI  - FASL polymorphism is associated with response to bacillus Calmette-Guerin
      immunotherapy in bladder cancer.
AB  - OBJECTIVE: Deregulation of FAS/FASL system may lead to immune escape and
      influence bacillus Calmette-Guerin (BCG) immunotherapy outcome, which is
      currently the gold standard adjuvant treatment for high-risk non-muscle invasive
      bladder tumors. Among other events, functional promoter polymorphisms of FAS and
      FASL genes may alter their transcriptional activity. Therefore, we aim to
      evaluate the role of FAS and FASL polymorphisms in the context of BCG therapy,
      envisaging the validation of these biomarkers to predict response. PATIENTS AND
      METHODS: DNA extracted from peripheral blood from 125 patients with bladder
      cancer treated with BCG therapy was analyzed by Polymerase Chain Reaction
      Restriction Fragment Length Polymorphism for FAS-670 A/G and FASL-844 T/C
      polymorphisms. FASL mRNA expression was analyzed by real-time Polymerase Chain
      Reaction. RESULTS: Carriers of FASL-844 CC genotype present a decreased
      recurrence-free survival after BCG treatment when compared with FASL-844 T allele
      carriers (mean 71.5 vs. 97.8 months, P = 0.030) and have an increased risk of BCG
      treatment failure (Hazard Ratio = 1.922; 95% Confidence Interval: [1.064-3.471];
      P = 0.030). Multivariate analysis shows that FASL-844 T/C and therapeutics scheme
      are independent predictive markers of recurrence after treatment. The evaluation
      of FASL gene mRNA levels demonstrated that patients carrying FASL-844 CC genotype
      had higher FASL expression in bladder tumors (P = 0.0027). Higher FASL levels
      were also associated with an increased risk of recurrence after BCG treatment
      (Hazard Ratio = 2.833; 95% Confidence Interval: [1.012-7.929]; P = 0.047). FAS
      670 A/G polymorphism analysis did not reveal any association with BCG therapy
      outcome. CONCLUSIONS: Our results suggest that analysis of FASL-844 T/C, but not
      FAS-670 A/G polymorphisms, may be used as a predictive marker of response to BCG
      immunotherapy.

PMID- 23948182
TI  - Pseudomonas aeruginosa-mannose-sensitive hemagglutinin inhibits epidermal growth
      factor receptor signaling pathway activation and induces apoptosis in bladder
      cancer cells in vitro and in vivo.
AB  - OBJECTIVES: Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA), a
      peritrichous P. aeruginosa strain with MSHA fimbriae, has been shown to be a
      valuable anticancer drug in many kinds of cancers. However, the effect of PA-MSHA
      on bladder cancer has not been elucidated. In this study, we focused on the
      antitumor activities and related mechanisms of PA-MSHA on bladder cancer in vitro
      and in vivo. MATERIALS AND METHODS: SV-40-immortalized normal uroepithelial cells
      (SV-HUC-1) and human bladder cancer cell lines (T24, 5637, and HT-1376) were
      treated with PA-MSHA or PA (heat-killed P. aeruginosa). At first, the effect of
      PA-MSHA on cancer cell proliferation was measured using Cell Counting Assay Kit-8
      (CCK-8), whereas the changes of cell morphology were observed by transmission
      electron microscopy. The early apoptosis induced by PA-MSHA was evaluated by flow
      cytometry, and the expression level of apoptosis-related molecules was detected
      using Western blot assay. We then investigated the activation of the epidermal
      growth factor receptor signaling pathway stimulated by PA-MSHA; the expression
      and phosphorylation of several key regulators involved in the EGFR signaling
      pathway were detected. At last, xenograft tumor in nude mice was used to further
      investigate the antitumor effect of PA-MSHA in vivo. RESULTS: Our results showed
      that PA-MSHA could efficiently inhibit proliferation and induce apoptosis in
      human bladder cancer cell lines. Furthermore, cells stimulated with PA-MSHA
      exhibited an inactivation of EGFR signaling. In vivo, PA-MSHA treatment
      significantly suppressed tumor growth and induced apoptosis in xenografts tumor
      in nude mice. CONCLUSIONS: PA-MSHA could efficiently inhibit proliferation and
      induce apoptosis in human bladder cancer cells in vitro and in vivo, which is
      associated with the inactivation of EGFR signaling pathway, and it might be used
      as a potential therapeutic agent for bladder cancer.

PMID- 23948183
TI  - Long-term cadmium exposure leads to the enhancement of lymphocyte proliferation
      via down-regulating p16 by DNA hypermethylation.
AB  - Cadmium (Cd) is a well-established carcinogen, however, the underlying mechanism,
      especially the role of epigenetics in it, is still poorly understood. Our
      previous work has disclosed that when rats were exposed to 0.5mg CdCl2 (kgd) for
      8 and 12 weeks, the growth of peripheral white blood cells (WBC) was obviously
      stimulated but no over-proliferation of granulocyte-monocyte (GM) progenitor
      cells was observed in the bone marrow, suggesting that the over-proliferation of
      lymphocyte was promoted by Cd exposure. Is DNA-methylation involved in this Cd
      stimulated cell proliferation? The present study found that when human B
      lymphoblast HMy2.CIR cells were exposed to Cd with a dose lower than 0.1MUM for 3
      months, both cell proliferation and mRNA expressions of DNA methyltransferases of
      DNMT1 and DNMT3b were increased, while the mRNA of tumor suppressor gene p16 was
      remarkably decreased. Furthermore, the level of genomic DNA methylation was
      increased and the CpG island in p16 promoter was hypermethylated in the Cd
      exposed cells. A DNA demethylating agent, 5-aza-2'-deoxycytidine (5-aza-dC),
      diminished Cd-stimulated cell proliferation associated with p16 overexpression.
      Our results suggested that the chronic exposure of low dose Cd could induce
      hypermethylation of p16 promoter and hence suppress p16 expression and then
      promote cell proliferation, which might contribute to Cd-induced carcinogenesis. 

PMID- 23948184
TI  - Factors influencing the retention of midwives in the public sector in
      Afghanistan: a qualitative assessment of midwives in eight provinces.
AB  - OBJECTIVE: to examine factors that affect retention of public sector midwives
      throughout their career in Afghanistan. DESIGN: qualitative assessment using semi
      structured in-depth interviews (IDIs) and focus group discussions (FGDs).
      SETTING: health clinics in eight provinces in Afghanistan, midwifery education
      schools in three provinces, and stakeholder organisations in Kabul. PARTICIPANTS:
      purposively sampled midwifery profession stakeholders in Kabul (n=14 IDIs);
      purposively selected community midwifery students in Kabul (n=3 FGDs), Parwan
      (n=1 FGD) and Wardak (n=1 FGD) provinces (six participants per FGD); public
      sector midwives, health facility managers, and community health workers from
      randomly selected clinics in eight provinces (n=48 IDIs); midwives who had left
      the public sector midwifery service (n=5 IDIs). MEASUREMENTS AND FINDINGS:
      several factors affect a midwife throughout her career in the public sector,
      including her selection as a trainee, the training itself, deployment to her pre
      assigned post, and working in clinics. Overall, appropriate selection is the key
      to ensuring deployment and retention later on in a midwife's career. Other
      factors that affect retention of midwives include civil security concerns in
      rural areas, support of family and community, salary levels, professional
      development opportunities and workplace support, and inefficient human resources
      planning in the public sector. KEY CONCLUSIONS: Factors affecting midwife
      retention are linked to problems within the community midwifery education (CME)
      programme and those reflecting the wider Afghan context. Civil insecurity and
      traditional attitudes towards women were major factors identified that negatively
      affect midwifery retention. IMPLICATIONS FOR PRACTICE: Factors such as civil
      insecurity and traditional attitudes towards women require a multisectoral
      response and innovative strategies to reduce their impact. However, factors
      inherent to midwife career development also impact retention and may be more
      readily modified.

PMID- 23948185
TI  - Immigrant women's experience of maternity services in Canada: a meta-ethnography.
AB  - OBJECTIVE: to synthesise data on immigrant women's experiences of maternity
      services in Canada. DESIGN: a qualitative systematic literature review using a
      meta-ethnographic approach METHODS: a comprehensive search strategy of multiple
      databases was employed in consultation with an information librarian, to identify
      qualitative research studies published in English or French between 1990 and
      December 2011 on maternity care experiences of immigrant women in Canada. A
      modified version of Noblit and Hare's meta-ethnographic theoretical approach was
      undertaken to develop an inductive and interpretive form of knowledge synthesis.
      The seven-phase process involved comparative textual analysis of published
      qualitative studies, including the translation of key concepts and meanings from
      one study to another to derive second and third-order concepts encompassing more
      than that offered by any individual study. ATLAS.ti qualitative data analysis
      software was used to store and manage the studies and synthesise their findings.
      FINDINGS: the literature search identified 393 papers, of which 22 met the
      inclusion criteria and were synthesised. The literature contained seven key
      concepts related to maternity service experiences including social (professional
      and informal) support, communication, socio-economic barriers, organisational
      environment, knowledge about maternity services and health care, cultural beliefs
      and practices, and different expectations between health care staff and immigrant
      women. Three second-order interpretations served as the foundation for two third
      order interpretations. Societal positioning of immigrant women resulted in
      difficulties receiving high quality maternity health care. Maternity services
      were an experience in which cultural knowledge and beliefs, and religious and
      traditional preferences were highly relevant as well but often overlooked in
      Canadian maternity settings. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: in
      order to implement woman-centered care, to enhance access to maternity services,
      and to promote immigrant women's health, it is important to consider these
      women's social position, cultural knowledge and beliefs, and traditional customs
      in the health care.

PMID- 23948186
TI  - Tools for endoscopic stricture dilation.

PMID- 23948188
TI  - Endoscopic innovations.

PMID- 23948187
TI  - Esophageal disease.

PMID- 23948189
TI  - EUS.

PMID- 23948190
TI  - Endoscopic tumor diagnosis and treatment.

PMID- 23948191
TI  - ERCP.

PMID- 23948192
TI  - Gastrointestinal bleeding.

PMID- 23948193
TI  - Capsule endoscopy and deep enteroscopy.

PMID- 23948194
TI  - Colonoscopy.

PMID- 23948195
TI  - Gastric antral web: a rare cause of gastric outlet obstruction treated with
      endoscopic therapy.

PMID- 23948196
TI  - Hemostatic powder as rescue therapy in a patient with H1N1 influenza with
      uncontrolled colon bleeding.

PMID- 23948197
TI  - The gallbladder polyp conundrum: a riddler on the wall.

PMID- 23948198
TI  - When is a fair bowel preparation fair enough?

PMID- 23948199
TI  - Cyanoacrylate spray for treatment of difficult-to-control GI bleeding.
AB  - BACKGROUND: Although endoscopic therapy is highly effective for control of GI
      bleeding, a small proportion of patients experience persistent bleeding and may
      require radiologic or surgical intervention. Experience with cyanoacrylate spray
      for treatment of difficult-to-control GI bleeding is limited. OBJECTIVE: To
      evaluate the efficacy and safety of an endoscopic cyanoacrylate spray technique
      for treatment of difficult-to-control GI bleeding. DESIGN: Case series. SETTING:
      Two tertiary-care centers. PATIENTS: This study involved consecutive patients
      with overt GI bleeding who were treated with n-butyl-2-cyanoacrylate spray during
      endoscopy for persistent bleeding despite conventional hemostatic therapies.
      INTERVENTION: Cyanoacrylate spray. MAIN OUTCOME MEASUREMENTS: Hemostasis,
      rebleeding, adverse events, and technical failure associated with cyanoacrylate
      spray. RESULTS: Five patients were treated with cyanoacrylate spray during
      endoscopy for persistent bleeding (duodenal ulcer in 3, gastric vascular ectasia
      in 1, rectal postpolypectomy bleeding in 1) after failed conventional therapies.
      Immediate hemostasis and technical success were achieved in all patients. At a
      median follow-up of 42 days (range 38-120 days), 2 patients developed recurrent
      bleeding. One patient experienced rebleeding 2 days after the procedure,
      subsequently requiring radiographic intervention and surgery. Another patient had
      recurrent bleeding from a different bleeding source 18 days after the procedure.
      No adverse events attributed to the cyanoacrylate spray were observed.
      LIMITATIONS: Small number of patients. CONCLUSION: In patients with difficult-to
      control GI bleeding failing conventional endoscopic therapies, cyanoacrylate
      spray was effective in achieving immediate hemostasis. Prospective studies with a
      larger number of patients to evaluate the role of the cyanoacrylate spray
      technique during endoscopy for GI bleeding are needed.

PMID- 23948200
TI  - Gastric heterotopic pancreas abscess leading to gastric outlet obstruction.

PMID- 23948201
TI  - The metallic silver sign with narrow-band imaging: a new endoscopic predictor for
      pharyngeal and esophageal neoplasia.

PMID- 23948202
TI  - Endoscopically assisted suturing of a persistent gastrocutaneous fistula by using
      a site closure device.

PMID- 23948203
TI  - The "Lasso" technique: snare-assisted endoscopic-radiological rendezvous
      technique for the management of complete transection of the main bile duct.

PMID- 23948204
TI  - Endoscopic treatment of Zenker's diverticulum: do we always need endoclips?

PMID- 23948205
TI  - Response.

PMID- 23948206
TI  - Response.

PMID- 23948207
TI  - Scoring system in upper GI bleeding.

PMID- 23948208
TI  - Effect of exogenous melatonin on embryo viability and uterine environment in
      undernourished ewes.
AB  - The effect of exogenous melatonin on embryo viability in undernourished ewes was
      investigated. At lambing, 24 ewes were treated (+MEL) or not (-MEL) with a
      melatonin implant. After 45 days, both groups were fed to provide 1.5 (Control,
      C) or 0.5 (Low, L) times daily maintenance requirements, so that experimental
      groups were: C-MEL, C+MEL, L-MEL and L+MEL. Ewes were mated (Day 0) and on Day 5
      embryos were recovered and classified according to their developmental stage and
      morphology. Ovaries were used for in vitro fertilization and uterine horns were
      processed to study progesterone and oestrogen receptor (PR and ERalpha)
      expression by inmunohistochemistry. After 21 days, groups L-MEL and L+MEL had an
      average weight loss of 10kg (P<0.001). Number of viable embryos per CL from L+MEL
      (0.50+/-0.2) was higher than from other groups (P<0.05). Overall, the melatonin
      effect was particularly evident in undernourished ewes, increasing both viability
      (L+MEL: 65%; L-MEL: 25%; P<0.05) and pregnancy rates (L+MEL: 66.6%; L-MEL: 16.6%;
      P<0.05). Neither nutrition and melatonin nor their interaction had a significant
      effect on the in vitro oocyte development. Melatonin treatment tended to increase
      the percentage of positive cells to PR in deep glandular epithelium,
      independently of diet (P=0.09), and the greatest staining intensity of PR was
      observed in the luminal and superficial glandular epithelia (P<0.0001). In
      conclusion, melatonin implants at lambing during the breeding season improve the
      viability of embryos recovered from undernourished ewes, although this effect
      seems not to be mediated at the oocyte competence level. 

PMID- 23948209
TI  - A disadvantage in bilingual sentence production modulated by syntactic frequency
      and similarity across languages.
AB  - Bilingual speakers access individual words less fluently, quickly, and accurately
      than monolinguals, particularly when accessing low-frequency words. Here we
      examined whether the bilingual speech production disadvantage would (a) extend to
      full sentences above and beyond single word retrieval and whether it would be
      modulated by (b) structural frequency and (c) syntactic properties of the
      bilingual speakers' other language. English monolinguals, Spanish-English
      bilinguals and Mandarin-English bilinguals were tested in a sentence production
      task conducted exclusively in English. Response times were modulated by
      bilingualism, structural frequency, and structural similarity across the
      bilingual speakers' two languages. These results refine our knowledge regarding
      the scope of the bilingual disadvantage, demonstrate that frequency effects apply
      to syntactic structures, and also suggest that syntax is partially shared across
      bilinguals' two languages. 

PMID- 23948210
TI  - Perspective tracking in progress: do not disturb.
AB  - Two experiments tested the hypothesis that indirect false-belief tests allow
      participants to track a protagonist's perspective uninterruptedly, whereas direct
      false-belief tests disrupt the process of perspective tracking in various ways.
      For this purpose, adults' performance was compared on indirect and direct false
      belief tests by means of continuous eye-tracking. Experiment 1 confirmed that the
      false-belief question used in direct tests disrupts perspective tracking relative
      to what is observed in an indirect test. Experiment 2 confirmed that perspective
      tracking is a continuous process that can be easily disrupted in adults by a
      subtle visual manipulation in both indirect and direct tests. These results call
      for a closer analysis of the demands of the false-belief tasks that have been
      used in developmental research. 

PMID- 23948211
TI  - The reversal of cognitive, but not negative or positive symptoms of
      schizophrenia, by the mGlu2/3 receptor agonist, LY379268, is 5-HT1A dependent.
AB  - mGlu(2/3) receptor agonists were shown to possess an antipsychotic-like potential
      in animal studies. Recent clinical investigations revealed that their
      antipsychotic potential might also manifest in humans. LY379268, the group II
      mGlu receptor orthosteric agonist, was previously shown to exhibit antipsychotic
      like action in animal models of schizophrenia. However, the mechanism of its
      action is not fully recognized. Here, we decided to investigate the involvement
      of 5-HT1A receptors in the LY379268-induced antipsychotic effects. We used models
      of positive, negative and cognitive symptoms of schizophrenia, such as MK-801-
      and amphetamine-induced hyperactivity tests, DOI-induced head twitches, social
      interaction and novel object recognition. LY379268 was active in a wide range of
      doses (0.5-5 mg/kg), depending on the paradigm. The effects of the drug were not
      antagonized by 5-HT(1A) antagonist, WAY100635 (0.1 mg/kg) in the models of
      positive and negative symptoms. Conversely, in the novel object recognition test,
      which exerts cognitive disturbances, the action of LY379268 was antagonized by
      WAY100635. Concomitantly, the action of a sub-effective dose of the drug was
      enhanced by the administration of a sub-effective dose of 5-HT(1A) agonist, (R)
      (+)-8-Hydroxy-DPAT. Altogether, we propose that the antipsychotic-like action of
      group II mGlu receptors' agonist is 5-HT(1A) independent in context of positive
      and negative symptoms, while the action toward cognitive disturbances seems to be
      5-HT(1A) dependent.

PMID- 23948212
TI  - Effects of endocannabinoid and endovanilloid systems on aversive memory
      extinction.
AB  - In contextual fear conditioning animals have to integrate various elemental
      stimuli into a coherent representation of the condition and then associate
      context representation with punishment. Although several studies indicated the
      modulating role of endocannabinoid system (ECS) on the associative learning, ECS
      effect on contextual fear conditioning requires further investigations. The
      present study assessed the effects of the increased endocannabinoid anandamide
      (AEA) tone on acquisition, retrieval and extinction of the contextual fear
      conditioning. Given that AEA may bind to cannabinoid type 1 (CB1) receptors as
      well as to postsynaptic ionotropic Transient Receptor Potential Vanilloid type 1
      (TRPV1) channels, particular attention was paid in determining how the increased
      AEA tone influenced fear responses. Furthermore, it was investigated how the ECS
      modulated the effects of stress-sensitization on fear response. Thus, mice
      submitted or not to a social defeat stress protocol were treated with drugs
      acting on ECS, CB1 receptors or TRPV1 channels and tested in a contextual fear
      conditioning whose conditioning, retrieval and extinction phases were analyzed.
      ECS activation influenced the extinction process and contrasted the stress
      effects on fear memory. Furthermore, CB1 receptor antagonist blocked and TRPV1
      channel antagonist promoted short- and long-term extinction. The present study
      indicates that ECS controls the extinction of aversive memories in the contextual
      fear conditioning. 

PMID- 23948213
TI  - Effects of social instability stress in adolescence on long-term, not short-term,
      spatial memory performance.
AB  - There is evidence that exposure to stressors in adolescence leads to lasting
      deficits on hippocampal-dependent tasks, but whether medial prefrontal cortical
      function is also impaired is unknown. We previously found that rats exposed to
      social instability stress in adolescence (SS; daily 1h isolation and subsequent
      change of cage partner between postnatal days 30 and 45) had impaired memory
      performance on a Spatial Object Location test and in memory for fear conditioning
      context, tasks that depend on the integrity of the hippocampus. Here we
      investigated whether impaired performance would be evident after adolescent SS in
      male rats on a different test of hippocampal function, spatial learning and
      memory in the Morris water maze (MWM) and on a working memory task for which
      performance depends on the integrity of the medial prefrontal cortex, the Delayed
      Alternation task (DAT). During MWM testing, SS rats showed greater improvements
      in performance across trials within days compared to control (CTL) rats, but
      showed less retention of learning between days (48 h) compared to CTL rats.
      Similarly, SS rats had impaired long-term memory in the Spatial Object Location
      test after a long delay (240 min), but not after shorter delays (15 or 60 min)
      compared to CTL rats. No group differences were observed on the DAT, which
      assessed working memory across brief delays (5-90 s). Thus, deficits in memory
      performance after chronic social stress in adolescence may be limited to long
      term memory.

PMID- 23948214
TI  - Role of insular cortex D1 and D2 dopamine receptors in nicotine self
      administration in rats.
AB  - The insular cortex has been associated with the processing of rewarding stimuli
      and with the neural bases of drug addiction. Ischemic damage to the insula has
      been associated with decreased desire to smoke cigarettes. Which component of
      insular function is involved in the neural basis of cigarette smoking is not
      clear. Dopamine systems are crucial for the reinforcing value of addictive drugs.
      The DA projection from the ventral tegmental area to the nucleus accumbens (NAc)
      has been shown to be a vital pathway for the primary reinforcement caused by
      taking a variety of abused drugs. In the current set of studies, the roles of D1
      and D2 receptors in the insular cortex in the self-administration of nicotine by
      rats were assessed. Adult female Sprague-Dawley rats were fitted with jugular
      catheters and given access to self-administer nicotine. Bilateral local infusion
      cannulae were implanted into the agranular insular cortex to locally administer
      D1 and D2 antagonists (SCH-23390 and haloperidol). Acute local infusions of the
      D1 antagonist SCH-23390 into the insula (1-2 MUg/side) significantly decreased
      nicotine self-administration by more than 50%. Repeated infusions of SCH-23390
      into the agranular insula caused continuing decreases in nicotine self
      administration without signs of tolerance. In contrast, local infusions of the D2
      antagonist haloperidol 0.5-2 MUg/side did not have any discernable effect on
      nicotine self-administration. These studies show the importance of DA D1 systems
      in the insula for nicotine reward.

PMID- 23948216
TI  - Special issue on optogenetics. Preface.

PMID- 23948215
TI  - Neuronal nitric oxide synthase and NADPH oxidase interact to affect cognitive,
      affective, and social behaviors in mice.
AB  - Both nitric oxide (NO) and reactive oxygen species (ROS) generated by nNOS and
      NADPH oxidase (NOX), respectively, in the brain have been implicated in an array
      of behaviors ranging from learning and memory to social interactions. Although
      recent work has elucidated how these separate redox pathways regulate neural
      function and behavior, the interaction of these two pathways in the regulation of
      neural function and behavior remains unspecified. Toward this end, the p47phox
      subunit of NOX, and nNOS were deleted to generate double knockout mice that were
      used to characterize the behavioral outcomes of concurrent impairment of the NO
      and ROS pathways in the brain. Mice were tested in a battery of behavioral tasks
      to evaluate learning and memory, as well as social, affective, and cognitive
      behaviors. p47phox deletion did not affect depressive-like behavior, whereas nNOS
      deletion abolished it. Both p47phox and nNOS deletion singly reduced anxiety-like
      behavior, increased general locomotor activity, impaired spatial learning and
      memory, and impaired preference for social novelty. Deletion of both genes
      concurrently had synergistic effects to elevate locomotor activity, impair
      spatial learning and memory, and disrupt prepulse inhibition of acoustic startle.
      Although preference for social novelty was impaired in single knockouts, double
      knockout mice displayed elevated levels of preference for social novelty above
      that of wild type littermates. These data demonstrate that, depending upon
      modality, deletion of p47phox and nNOS genes have dissimilar, similar, or
      additive effects. The current findings provide evidence that the NOX and nNOS
      redox signaling cascades interact in the brain to affect both cognitive function
      and social behavior. 

PMID- 23948217
TI  - Increased nitric oxide-mediated neurotransmission in the medial prefrontal cortex
      is associated with the long lasting anxiogenic-like effect of predator exposure.
AB  - Posttraumatic stress disorder (PTSD) is an anxiety disorder caused by the
      experience of a severe traumatic event. In rats this disorder has been modeled by
      exposure to a predator threat. PTSD has been associated to structural and
      functional changes in the medial prefrontal cortex (mPFC). Direct injections into
      this brain region of glutamate antagonists or inhibitors of the nitric oxide
      synthase (NOS) enzyme cause anxiolytic-like effects in rodents. In the present
      work we investigated if the behavioral changes induced by predator exposure are
      associated with changes in the mPFC nitrergic system. Since the hippocampus,
      amygdala and dorsal periaqueductal grey have also been associated to anxiety
      disorders, including PTSD, we also verified if this procedure would modify the
      nitrergic system in these regions. Male Wistar rats were exposed to a dummy or
      live cat for ten minutes and tested in the elevated plus maze test (EPM) seven
      days later. Immediately after the test their brains were removed for neuronal NOS
      (nNOS) immunohistochemistry detection and measurements of nitrite/nitrate (NOx)
      levels. Exposure to the live cat increased freezing responses. One week later the
      animals that froze when confronted with the cat presented a decreased percentage
      of entries in the open arms of the EPM and an increased number of nNOS positive
      neurons in the mPFC and basolateral nucleus of amygdala, but not in the
      hippocampus, central and medial nuclei of amygdaloid complex or dorsal-lateral
      periaqueductal grey. Moreover, cat exposed animals showed increased NOx levels in
      the mPFC but not in the hippocampus one week later. The number of nNOS neurons
      and NOx levels in the mPFC showed a significant correlation with freezing time
      during cat exposure. Our results suggest that plastic modifications of the
      nitrergic system in the mPFC could be related to long lasting behavioral changes
      induced by severe traumatic events such as predator exposure. 

PMID- 23948218
TI  - Developing 'integrative' zebrafish models of behavioral and metabolic disorders.
AB  - Recently, the pathophysiological overlap between metabolic and mental disorders
      has received increased recognition. Zebrafish (Danio rerio) are rapidly becoming
      a popular model organism for translational biomedical research due to their
      genetic tractability, low cost, quick reproductive cycle, and ease of behavioral,
      pharmacological or genetic manipulation. High homology to mammalian physiology
      and the availability of well-developed assays also make the zebrafish an
      attractive organism for studying human disorders. Zebrafish neurobehavioral and
      endocrine phenotypes show promise for the use of zebrafish in studies of stress,
      obesity and related behavioral and metabolic disorders. Here, we discuss the
      parallels between zebrafish and other model species in stress and obesity
      physiology, as well as outline the available zebrafish models of weight gain,
      metabolic deficits, feeding, stress, anxiety and related behavioral disorders.
      Overall, zebrafish demonstrate a strong potential for modeling human behavioral
      and metabolic disorders, and their comorbidity. 

PMID- 23948219
TI  - A possible negative influence of depression on the ability to overcome memory
      interference.
AB  - Pattern separation is a mechanism for encoding memories, whereby distinct memory
      representations are created for very similar stimuli and events. It has been
      proposed that depression negatively impacts pattern separation abilities.
      However, a link between depression and performance in memory tasks requiring
      pattern separation is still unclear even though it is well established that
      depression is associated with reduced declarative memory performance and
      decreased hippocampal volume. Accordingly, we designed a study to investigate the
      relationship between pattern separation performance and the severity of
      depression symptoms in an otherwise healthy population. Participants completed a
      pattern separation memory test and a set of questionnaires to gauge their level
      of depression. We found a negative relationship between depression scores and
      pattern separation scores. These results provide support for the idea that
      depression is negatively related to pattern separation performance. 

PMID- 23948221
TI  - Effect of continuous positive airway pressure treatment on short-term memory
      performance over 24 h of sustained wakefulness in patients with obstructive sleep
      apnea-hypopnea syndrome.
AB  - BACKGROUND: Few studies have examined the impact of continuous positive airway
      pressure (CPAP) therapy on short-term memory (STM) over sustained wakefulness in
      patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). We have
      investigated if impaired STM can be reversed by CPAP treatment in a 24-h
      sustained wakefulness paradigm. METHODS: Our follow-up study was conducted with
      repeated-memory tasks within 12 OSAHS patients and 10 healthy controls who
      underwent three 32-h sessions, one before CPAP (T0) and the second (T3) and the
      third (T6), after 3 and 6 months of treatment, respectively, for OSAHS patients.
      Each session included one night of sleep followed by 24h of sustained
      wakefulness, during which both groups performed STM tasks including both digit
      span (DS) and Sternberg tasks. RESULTS: Untreated OSAHS patients had no deficit
      in the forward DS task measuring immediate memory but were impaired in STM,
      especially working memory assessed by the complex Sternberg task and the backward
      DS. However, only performance in the latter was improved after 6 months of CPAP
      treatment. CONCLUSIONS: Because the high level of memory scanning required high
      speed in information processing, persistent impairment on the complex Sternberg
      task may be attributable to working memory slowing, possibly enhanced by
      sustained wakefulness.

PMID- 23948220
TI  - Clinical markers of early nigrostriatal neurodegeneration in idiopathic rapid eye
      movement sleep behavior disorder.
AB  - BACKGROUND: Rapid eye movement sleep behavior disorder (RBD) is an early feature
      in alpha synucleinopathies and may precede other clinical manifestations of
      disease for several years. Olfactory dysfunction and mild motor abnormalities
      (MMAs) are highly prevalent in prodromal alpha synucleinopathies such as RBD and
      are suspected to be predictive neurodegenerative markers. Because both markers
      also are highly prevalent in the healthy elderly population, the discriminative
      value to detect an early neurodegenerative process is unclear. METHODS: We
      examined 28 patients with idiopathic RBD (iRBD) without manifest
      neurodegenerative disease to determine diagnostic accuracy of MMAs and olfactory
      dysfunction in identifying patients with early nigrostriatal degeneration in
      transcranial sonography (TCS) and (123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)
      N-(3-fluoropropyl)-nortropane single-photon emission computed tomography ((123)I
      FP-CIT-SPECT). RESULTS: Sixty-three percent of our participants showed MMAs which
      were strongly associated with abnormal TCS and (123)I-FP-CIT-SPECT findings. The
      discriminative value in detecting participants with early nigrostriatal
      degeneration was excellent (area under the receiver operating characteristic
      [ROC] curve, 0.84 [P<=.003] for TCS and 0.79 [P<=.066] for (123)I-FP-CIT-SPECT).
      Olfactory dysfunction was present in 78% of iRBD participants, but it was not
      linked with neuroimaging abnormalities or MMAs. Olfactory dysfunction did not
      discriminate participants with early nigrostriatal degeneration (area under the
      ROC curve, 0.54 [P<=.747] for TCS and 0.31 [P<=.225] for (123)I-FP-CIT-SPECT).
      Early RBD manifestation but no demographic (e.g., age, gender) or clinical
      characteristics of RBD (e.g., duration, severity of RBD) were associated with
      neuroimaging abnormalities in TCS and (123)I-FP-CIT-SPECT. CONCLUSIONS: Unlike
      olfactory dysfunction, MMAs discriminate patients with early nigrostriatal
      degeneration in iRBD. Early RBD manifestation seems to be an additional risk
      factor which aggravates neurodegenerative risk.

PMID- 23948222
TI  - Sensory symptoms in restless legs syndrome: the enigma of pain.
AB  - Restless legs syndrome (RLS) is a common sensorimotor condition characterized by
      an urge to move the legs, worsening of symptoms at rest and during the
      evening/night, and improvement of symptoms with movement. Our review explores the
      role and impact of sensory symptoms in RLS. The phenomenology of RLS is
      discussed, highlighting the difficulty patients have in describing their
      sensations and in differentiating between sensory and motor symptoms. Sensory
      symptoms have a significant impact on quality of life but remain much less well
      understood than motor symptoms and sleep disturbances in RLS. Although RLS
      symptoms usually are not described as painful, sensory manifestations in RLS do
      share some similarities with chronic pain sensations, and RLS frequently occurs
      in chronic pain and neuropathic conditions. Peripheral neuropathies may account
      for some of the sensory disturbances in secondary RLS, while alterations in
      central somatosensory processing may be a more viable explanation for the sensory
      disturbances in primary RLS. The effectiveness of analgesics in treating RLS
      supports the concept of abnormal sensory modulation in RLS and suggests an
      overlap between pain modulatory pathways and sensory disturbances. Future studies
      are needed to better understand the experiential and biologic aspects of altered
      sensory experiences in RLS. 

PMID- 23948223
TI  - Insight into metabolic and cometabolic activities of autotrophic and
      heterotrophic microorganisms in the biodegradation of emerging trace organic
      contaminants.
AB  - Many efforts have been made to understand the biodegradation of emerging trace
      organic contaminants (EOCs) in the natural and engineered systems. This review
      summarizes the current knowledge on the biodegradation of EOCs while having in
      depth discussion on metabolism and cometabolism of EOCs. Biodegradation of EOCs
      is mainly attributed to cometabolic activities of both heterotrophic and
      autotrophic microorganisms. Metabolism of EOCs can only be observed by
      heterotrophic microbes. Autotrophic ammonia oxidizing bacteria (AOB) and ammonia
      oxidizing archaeal (AOA) cometabolize a variety of EOCs via the non-specific
      enzymes, such as ammonia monooxygenase (AMO). Higher biodegradation of EOCs is
      often noted under nitrification at high ammonia loading rate. The presence of a
      growth substrate promotes cometabolic biodegradation of EOCs. Potential
      strategies for enhancing the biodegradation of EOCs were also proposed in this
      review. 

PMID- 23948224
TI  - Accelerated azo dye removal by biocathode formation in single-chamber
      biocatalyzed electrolysis systems.
AB  - Biocatalyzed electrolysis systems (BES) have been the topic of a great deal of
      research. However, the biocathodes formed in single-chamber BES without extra
      inocula have not previously been researched. Along with the formation of
      biocathodes, the polarization current increased to 1.76 mA from 0.35 mA of abio
      cathodes at -1.2 V (vs. SCE). Electrochemical impedance spectroscopy (EIS)
      results also indicated that the charge transfer resistance (Rct) was decreased to
      148.9 Omega, less than 1978 Omega of the abio-cathodes cleared. The performance
      of the biocathodes was tested for azo dye decolorization, and the dye removal
      efficiency was 13.3+/-3.2% higher than abio-cathodes with a 0.5 V direct current
      (DC) power supply. These aspects demonstrate that biocathode accelerates the rate
      of electrode reaction in BES and comparing with noble metal catalysts,
      biocathodes have low toxicity or non-toxic and reproducible properties, which can
      be widely applied in bioelectrochemical field in the future.

PMID- 23948225
TI  - Effect of endogenous hydrolytic enzymes pretreatment on the anaerobic digestion
      of sludge.
AB  - In this study, the effects of endogenous amylase, endogenous protease and
      combined amylase/protease pretreatment of sludge were studied to enhance the
      efficiency of sludge anaerobic digestion. These enzymes were obtained from
      bacterial fermentation and bacteria were separated from the sludge. All
      treatments improved sludge solubilization and acidification but had little
      influence on the floc sizes. In terms of sludge solubilization and acidification
      amylase was better than protease or mixed enzyme. After 7 h endogenous amylase
      treatment, the supernatant soluble chemical oxygen demand and volatile fatty
      acids concentration increased by 78.2% and 129.6%, respectively. But, in terms of
      anaerobic biodegradability, the best result was obtained with combined enzyme
      treatment, biogas production increased by 23.1% compared to the control after 11
      days of anaerobic digestion. Scanning electron micrographs observation and
      particle size analysis revealed that the most important mechanism for the enzyme
      treatment of sludge might be solubilization of extracellular polymeric
      substances.

PMID- 23948227
TI  - Vaccination with Flt3L-induced CD8alpha+ dendritic cells prevents CD4+ T helper
      cell-mediated experimental autoimmune myocarditis.
AB  - Experimental autoimmune myocarditis (EAM) represents a CD4(+) T helper (Th) cell
      mediated mouse model of inflammatory heart disease. Interferon (IFN)-gamma,
      typically produced by Th1 cells, reduces EAM severity in myosin heavy-chain
      (MyHC)-alpha peptide/Complete Freund adjuvant-immunized mice. Thus, developing a
      vaccination strategy that promotes differentiation of Th1 cells may be beneficial
      in EAM. FMS-like tyrosine kinase 3 ligand (Flt3L)-induced splenic CD8alpha(+)
      dendritic cells (DC), which produce interleukin (IL)-12p35, were identified to
      selectively induce biased differentiation towards Th1. Mice vaccinated with MyHC
      alpha-loaded Flt3L-induced splenic CD8alpha(+) DC were protected from EAM. In
      contrast, when Flt3L-induced splenic CD8alpha(+) DC were pre-stimulated and over
      activated with LPS and alphaCD40 antibodies or loaded with unspecific OVA(323
      339) peptide instead of MyHC-alpha peptide, mice developed similar disease scores
      as non-vaccinated controls. Vaccination efficacy depended on IFN-gamma, since
      CD8alpha(+)-vaccinated IFN-gammaR(-/-) mice were not protected. Importantly,
      splenic CD8alpha(+) vaccination was independent of regulatory T cells. Taken
      together, Flt3L-induced dendritic cell-based antigen-specific vaccination limits
      expansion of auto-reactive Th cells and protects mice from autoimmune heart
      inflammation.

PMID- 23948226
TI  - PKC independent inhibition of voltage gated calcium channels by volatile
      anesthetics in freshly isolated vascular myocytes from the aorta.
AB  - In this study we used barium currents through voltage gated L-type calcium
      channels (recorded in freshly isolated cells with a conventional patch-clamp
      technique) to elucidate the cellular action mechanism for volatile anesthetics.
      It was found that halothane and isoflurane inhibited (dose-dependently and
      voltage independently) Ba2+ currents through voltage gated Ca2+ channels. Half
      maximal inhibitions occurred at 0.64 +/- 0.07 mM and 0.86 +/- 0.1 mM. The Hill
      slope value was 2 for both volatile anesthetics, suggesting the presence of more
      than one interaction site. Current inhibition by volatile anesthetics was
      prominent over the whole voltage range without changes in the peak of the current
      voltage relationship. Intracellular infusion of the GDPbetaS (100 MUM) together
      with staurosporine (200 nM) did not prevent the inhibitory effect of volatile
      anesthetics. Unlike pharmacological Ca2+ channel blockers, volatile anesthetics
      blocked Ca2+ channel currents at resting membrane potentials. In other words,
      halothane and isoflurane induced an 'initial block'. After the first 4-7 control
      pulses, the cells were left unstimulated and anesthetics were applied. The first
      depolarization after the pause evoked a Ca2+ channel current whose amplitude was
      reduced to 41 +/- 3.4% and to 57 +/- 4.2% of control values. In an analysis of
      the steady-state inactivation curve for voltage dependence, volatile anesthetics
      induced a negative shift of the 50% inactivation of the calcium channels. By
      contrast, the steepness factor characterizing the voltage sensitivity of the
      channels was unaffected. Unitary L-type Ca2+ channels blockade occurred under
      cell-attached configuration, suggesting a possible action of volatile anesthetics
      from within the intracellular space or from the part of the channel inside the
      lipid bilayer.

PMID- 23948228
TI  - Reprint of: Factors associated with effectiveness of the first dose of hepatitis
      B vaccine in China: 1992-2005.
AB  - BACKGROUND: In China, the prevalence of chronic hepatitis B infection was high
      because of perinatal and early childhood transmission. A three-dose hepatitis B
      vaccine schedule with a first dose as soon as possible after birth was introduced
      in 1992 and generalized in 2002 in the Expanded Programme of Immunization (EPI).
      In 2006, a serological survey evaluated the effectiveness of vaccination.
      METHODS: We conducted a restricted analysis of the national serological survey
      that sampled children and collected information on demographic characteristics,
      birth history, hepatitis B vaccination and hepatitis B surface antigen (HBsAg)
      status as determined by ELISA testing. We compared children who received the
      first dose in a timely way (i.e., within 24h of birth) with others in terms of
      HBsAg status, stratified by birth cohort and place of birth. RESULTS: Three-dose
      hepatitis B vaccine coverage increased from 60.8% for children born in 1992-1997
      to 93.2% for children born in 2002-2005. Meanwhile, timely birth dose coverage
      increased from 38.7% to 74.4%. Among 29,410 children born in 1992-2005 who had
      received three vaccine doses and no hepatitis B immune globulin, factors
      associated with being HBsAg-negative in multivariate analysis included receiving
      a timely birth dose (p=0.04), birth after 1998 (p<0.001), living in an urban
      setting (p=0.008) and hospital birth (p=0.001). The relative prevalence of HBsAg
      among children receiving the timely birth dose was lower for children born in
      county or larger hospitals (0.39), intermediate in township hospitals (0.73) and
      highest at home (0.87). CONCLUSIONS: Hospital birth and receiving a timely birth
      dose are the main determinants of the field effectiveness of the first dose of
      hepatitis B vaccine. Efforts to increase the proportion of hospital deliveries
      are key to increasing timely birth dose coverage and its effectiveness.

PMID- 23948229
TI  - Reprint of: Epidemiological serosurvey of Hepatitis B in China--declining HBV
      prevalence due to Hepatitis B vaccination.
AB  - OBJECTIVE: To determine the prevalence of hepatitis B surface antigen (HBsAg),
      hepatitis B surface antibody (anti-HBs), and hepatitis B core anti-body (anti
      HBc) in a representative population in China 14 years after introduction of
      hepatitis B vaccination of infants. METHODS: National serosurvey, with
      participants selected by multi-stage random sampling. Demographics and hepatitis
      B vaccination history collected by questionnaire and review of vaccination
      records, and serum tested for HBsAg, antibody to anti-HBc and anti-HBs by ELISA.
      FINDINGS: The weighted prevalences of HBsAg, anti-HBs and anti-HBc for Chinese
      population aged 1-59 years were 7.2%, 50.1%, 34.1%, respectively. HBsAg
      prevalence was greatly diminished among those age <15 years compared to that
      found in the 1992 national serosurvey, and among children age <5 years was only
      1.0% (90% reduction). Reduced HBsAg prevalence was strongly associated with
      vaccination among all age groups. HBsAg risk in adults was associated with male
      sex, Western region, and certain ethnic groups and occupations while risk in
      children included birth at home or smaller hospitals, older age, and certain
      ethnic groups (Zhuang and other). CONCLUSIONS: China has already reached the
      national goal of reducing HBsAg prevalence to less than 1% among children under 5
      years and has prevented an estimated 16-20 million HBV carriers through hepatitis
      B vaccination of infants. Immunization program should be further strengthened to
      reach those remaining at highest risk.

PMID- 23948230
TI  - Measles virus expressed Helicobacter pylori neutrophil-activating protein
      significantly enhances the immunogenicity of poor immunogens.
AB  - Helicobacter pylori neutrophil-activating protein (NAP) is a toll-like receptor 2
      (TLR2) agonist and potent immunomodulator inducing Th1-type immune response. Here
      we present data about characterization of the humoral immune response against NAP
      tagged antigens, encoded by attenuated measles virus (MV) vector platform, in MV
      infection susceptible type I interferon receptor knockout and human CD46
      transgenic (Ifnarko-CD46Ge) mice. Immunogenicity of MV expressing a full-length
      human immunoglobulin lambda light chain (MV-lambda) was compared to that of MV
      expressing lambda-NAP chimeric protein (MV-lambda-NAP). MV-lambda-NAP immunized
      Ifnarko-CD46Ge mice developed significantly higher (6-20-fold) anti-lambda ELISA
      titers as compared to the MV-lambda-immunized control animal group, indicating
      that covalently-linked NAP co-expression significantly enhanced lambda
      immunogenicity. In contrast, ELISA titers against MV antigens were not
      significantly different between the animals vaccinated with MV-lambda or MV
      lambda-NAP. NAP-tagged antigen expression did not affect development of
      protective anti-measles immunity. Both MV-lambda and MV-lambda-NAP-immunized
      groups showed strong virus neutralization serum titers in plaque reduction
      microneutralization test. These results demonstrated that MV-encoded lambda-NAP
      is highly immunogenic as compared to the unmodified full-length lambda chain.
      Boost of immune response to poor immunogens using live vectors expressing NAP
      tagged chimeric antigens is an attractive approach with potential application in
      immunoprophylaxis of infectious diseases and cancer immunotherapy. 

PMID- 23948232
TI  - Ionizing radiation and genetic risks. XVII. Formation mechanisms underlying
      naturally occurring DNA deletions in the human genome and their potential
      relevance for bridging the gap between induced DNA double-strand breaks and
      deletions in irradiated germ cells.
AB  - While much is known about radiation-induced DNA double-strand breaks (DSBs) and
      their repair, the question of how deletions of different sizes arise as a result
      of the processing of DSBs by the cell's repair systems has not been fully
      answered. In order to bridge this gap between DSBs and deletions, we critically
      reviewed published data on mechanisms pertaining to: (a) repair of DNA DSBs (from
      basic studies in this area); (b) formation of naturally occurring structural
      variation (SV) - especially of deletions - in the human genome (from genomic
      studies) and (c) radiation-induced mutations and structural chromosomal
      aberrations in mammalian somatic cells (from radiation mutagenesis and radiation
      cytogenetic studies). The specific aim was to assess the relative importance of
      the postulated mechanisms in generating deletions in the human genome and examine
      whether empirical data on radiation-induced deletions in mouse germ cells are
      consistent with predictions of these mechanisms. The mechanisms include (a) NHEJ,
      a DSB repair process that does not require any homology and which functions in
      all stages of the cell cycle (and is of particular relevance in G0/G1); (b) MMEJ,
      also a DSB repair process but which requires microhomology and which presumably
      functions in all cell cycle stages; (c) NAHR, a recombination-based DSB repair
      mechanism which operates in prophase I of meiosis in germ cells; (d) MMBIR, a
      microhomology-mediated, replication-based mechanism which operates in the S phase
      of the cell cycle, and (e) strand slippage during replication (involved in the
      origin of small insertions and deletions (INDELs). Our analysis permits the
      inference that, between them, these five mechanisms can explain nearly all
      naturally occurring deletions of different sizes identified in the human genome,
      NAHR and MMBIR being potentially more versatile in this regard. With respect to
      radiation-induced deletions, the basic studies suggest that those arising as a
      result of the operation of NHEJ/MMEJ processes, as currently formulated, are
      expected to be relatively small. However, data on induced mutations in mouse
      spermatogonial stem cells (irradiation in G0/G1 phase of the cell cycle and DSB
      repair presumed to be via NHEJ predominantly) show that most are associated with
      deletions of different sizes, some in the megabase range. There is thus a
      'discrepancy' between what the basic studies suggest and the empirical
      observations in mutagenesis studies. This discrepancy, however, is only an
      apparent but not a real one. It can be resolved by considering the issue of
      deletions in the broader context of and in conjunction with the organization of
      chromatin in chromosomes and nuclear architecture, the conceptual framework for
      which already exists in studies carried out during the past fifteen years or so.
      In this paper, we specifically hypothesize that repair of DSBs induced in
      chromatin loops may offer a basis to explain the induction of deletions of
      different sizes and suggest an approach to test the hypothesis. We emphasize that
      the bridging of the gap between induced DSB and resulting deletions of different
      sizes is critical for current efforts in computational modeling of genetic risks.

PMID- 23948231
TI  - Sox2 modulates the function of two distinct cell lineages in mouse skin.
AB  - In postnatal skin the transcription factor Sox2 is expressed in the dermal
      papilla (DP) of guard/awl/auchene hair follicles and by mechanosensory Merkel
      cells in the touch domes of guard hairs. To investigate the consequences of Sox2
      ablation in skin we deleted Sox2 in DP cells via Blimp1Cre and in Merkel cells
      via K14Cre. Loss of Sox2 from the DP did not inhibit hair follicle morphogenesis
      or establishment of the dermis and hypodermis. However, Sox2 expression in the DP
      was necessary for postnatal maintenance of awl/auchene hair follicles. Deletion
      of Sox2 via K14Cre resulted in a decreased number of Merkel cells but had no
      effect on other epithelial compartments or on the dermis. The reduced number of
      Merkel cells did not affect the number or patterning of guard hairs, nerve
      density or the interaction of nerve cells with the touch domes. We conclude that
      Sox2 is a marker of two distinct lineages in the skin and regulates the number of
      differentiated cells in the case of the Merkel cell lineage and hair follicle
      type in the case of the DP.

PMID- 23948233
TI  - Pathology report assessment of incidental gallbladder carcinoma diagnosed from
      cholecystectomy specimens: results of a French multicentre survey.
AB  - AIMS: To assess the accuracy of pathology reports on gallbladder specimens from
      patients operated on for incidental gallbladder carcinoma. METHODS: Demographic
      data, details on pathological reports including gross and microscopic features
      section were recorded in 100 selected patients with incidental gallbladder
      carcinoma diagnosed from 2004 to 2007. RESULTS: Pathology reports had a
      conventional format in 93% of cases, without any standardization. Turnaround time
      ranged from 1 to 35 days. Frozen sections were performed in 20% of cases. The
      reports failed to give information on prognostic histological factors: exact
      tumour site (missing in 55% of cases), depth of tumour infiltration within the
      gallbladder wall (missing in 10%), surgical margins (missing in 40% for the
      cystic duct margin), tumour differentiation (missing in 28%), vascular invasion
      (missing in 52%) and perineural invasion (missing in 51%). Lymph node status
      could be assessed in 44% of cases. Distances between the tumour and the cystic
      duct and circumferential margins were not specified in 68% and 84% of cases. Only
      29% of the reports clearly stated the pTNM stage in the conclusion section. The
      pT stage with margin status and tumour site was only mentioned in 30% of the
      reports. CONCLUSION: Pathology reports on gallbladder carcinoma from
      participating centres frequently lacked important information on key prognostic
      histological factors.

PMID- 23948234
TI  - Transcriptional hierarchies regulating early blood cell development.
AB  - Hematopoiesis represents one of the paradigmatic systems for studying stem cell
      biology, but our understanding of how the hematopoietic system develops during
      embryogenesis is still incomplete. While many lessons have been learned from
      studying the mouse embryo, embryonic stem cells have come to the fore as an
      alternative and more tractable model to recapitulate hematopoietic development.
      Here we review what is known about the embryonic origin of blood from these
      complementary systems and how transcription factor networks regulate the
      emergence of hematopoietic tissue from the mesoderm. Furthermore, we have
      performed an integrated analysis of genome-wide microarray and ChIP-seq data sets
      from mouse embryos and embryonic stem (ES) cell lines deficient in key regulators
      and demonstrate how this type of analysis can be used to reconstruct regulatory
      hierarchies that both confirm existing regulatory linkages and suggest additional
      interactions. 

PMID- 23948235
TI  - Logistic regression modeling to assess groundwater vulnerability to contamination
      in Hawaii, USA.
AB  - Capture zone analysis combined with a subjective susceptibility index is
      currently used in Hawaii to assess vulnerability to contamination of drinking
      water sources derived from groundwater. In this study, we developed an
      alternative objective approach that combines well capture zones with multiple
      variable logistic regression (LR) modeling and applied it to the highly-utilized
      Pearl Harbor and Honolulu aquifers on the island of Oahu, Hawaii. Input for the
      LR models utilized explanatory variables based on hydrogeology, land use, and
      well geometry/location. A suite of 11 target contaminants detected in the region,
      including elevated nitrate (>1 mg/L), four chlorinated solvents, four
      agricultural fumigants, and two pesticides, was used to develop the models. We
      then tested the ability of the new approach to accurately separate groups of
      wells with low and high vulnerability, and the suitability of nitrate as an
      indicator of other types of contamination. Our results produced contaminant
      specific LR models that accurately identified groups of wells with the
      lowest/highest reported detections and the lowest/highest nitrate concentrations.
      Current and former agricultural land uses were identified as significant
      explanatory variables for eight of the 11 target contaminants, while elevated
      nitrate was a significant variable for five contaminants. The utility of the
      combined approach is contingent on the availability of hydrologic and chemical
      monitoring data for calibrating groundwater and LR models. Application of the
      approach using a reference site with sufficient data could help identify key
      variables in areas with similar hydrogeology and land use but limited data. In
      addition, elevated nitrate may also be a suitable indicator of groundwater
      contamination in areas with limited data. The objective LR modeling approach
      developed in this study is flexible enough to address a wide range of
      contaminants and represents a suitable addition to the current subjective
      approach.

PMID- 23948236
TI  - Endoscopic management for pancreatic injuries due to blunt abdominal trauma
      decreases failure of nonoperative management and incidence of pancreatic-related
      complications.
AB  - INTRODUCTION: The actual benefit of endoscopic techniques in the non-operative
      management (NOM) of pancreatic injury is still unclear, with its role and
      effectiveness in the NOM of pancreatic injury remains defined and doubted. The
      purpose of this study was to evaluate the feasibility and long-term results of
      endoscopic techniques in the NOM of blunt pancreatic injury, and to determine
      whether NOM can be performed safely for selective patients with pancreatic
      injury. PATIENTS AND METHODS: The records and follow-up data of all patients with
      blunt pancreatic injuries over 16-year period from October 1, 1996, to September
      30, 2012 at our department were retrospectively reviewed. Failure of NOM (FNOM)
      occurred if laparotomy was required after attempted NOM. RESULTS: 132 patients
      (32% of all patients with blunt pancreatic injury) underwent NOM, including 58
      who underwent endoscopic management (EM) and 74 who were observed without EM (NO
      EM). FNOM of overall NOM was 20%, including 30% of NO-EM and 9% of EM. There was
      no significant difference in FNOM for NO-EM versus EM for grade I, however, a
      significant decrease in FNOM was noted with the addition of EM for grade II and
      III. EM was a statistically significant independent risk factor. Regular follow
      up of 1 year showed that, for patients from grade I to III, 53 patients (42%)
      from operative management (OM) and 34 patients (46%) of the NO-EM developed
      various pancreatic-related complications, while only 15 patients (26%) of the EM
      developed such complications, and the difference was significant. CONCLUSION:
      Application of strictly defined selection criteria for NOM and EM in patients
      with blunt pancreatic injury resulted in one of the lowest FNOM rates (9%) and
      pancreatic-related complications incidence (25%). Selective application of EM for
      hemodynamically stable patients with blunt pancreatic injury will extend the
      indications for, and improve success of NOM.

PMID- 23948237
TI  - Development of a solid phase extraction method for the simultaneous determination
      of steroid hormones in H295R cell line using liquid chromatography-tandem mass
      spectrometry.
AB  - The H295R in vitro cell line produces the majority of the steroidogenesis, for
      which reason it is commonly used as a screening tool for endocrine disrupting
      chemicals. Simultaneous determination of the precursor cholesterol and key
      steroid hormones could give a broad insight into the mechanistic disruption of
      the steroidogenesis. Steroid hormones have primarily been extracted from H295R
      incubation medium by means of liquid-liquid extraction (LLE) and the obtained
      recoveries and matrix effects have typically not been stated or assessed. In the
      present study a solid-phase extraction (SPE) method was developed and validated
      for the simultaneous extraction of cholesterol and five key steroid hormones
      pregnenolone, 17-hydroxyprogesterone, testosterone, cortisol and aldosterone from
      H295R incubation medium, and finally detected by LC-MS/MS. Cholesterol was
      recovered at a level of 55.7%, while steroid hormone recoveries ranged from 98.2
      to 109.4%. Matrix effects varied between -0.6% and 62.8%. Intra-day precision was
      deemed acceptable, but the inter-day precision for pregnenolone and aldosterone
      exceeded the precision limit of 15% RSD. Although LLE has been the most
      frequently used extraction method in H295R studies, however, our investigation
      has shown that SPE may relatively easily extract and recover steroid hormones,
      potentially replacing LLE. 

PMID- 23948238
TI  - Isolation, identification and pharmacokinetic analysis of fructosyl puerarins
      from enzymatic glycosylation.
AB  - A method of using high-speed counter-current chromatography (HSCCC) was
      established for preparative isolation and purification of puerarin glycosides
      from the crude sample after enzymatic glycosylation of puerarin. Four fructosyl
      puerarins were successfully purified for the first time by HSCCC with a two-phase
      solvent system composed of n-butanol-acetic acid-water (4:1.5:6, v/v/v). A total
      of 5mg of puerarin (1), 20mg of beta-d-fructofuranosyl-(2->6)-puerarin (2), 41mg
      of beta-d-difructofuranosyl-(2->6)-puerarin (3), 18mg of beta-d
      trifructofuranosyl-(2->6)-puerarin (4) and 15mg beta-d-tetrafructofuranosyl-(2
      >6)-puerarin (5) were obtained in one-step separation from 100mg of the crude
      sample with purities of 98.5%, 98.3%, 98.9%, 97.8%, 97.5% and 97.2%,
      respectively. Among them, compounds 2-5 are novel compounds, and their chemical
      structures were identified by HRMS, (1)H NMR, (13)C NMR and 2D NMR.
      Pharmacokinetic analysis showed that beta-d-fructofuranosyl-(2->6)-puerarin (2)
      was able to maintain higher plasma concentrations and have a longer mean
      residence time in the blood than puerarin. 

PMID- 23948239
TI  - The added value of measuring thumb and finger strength when comparing strength
      measurements in hypoplastic thumb patients.
AB  - BACKGROUND: When interventions to the hand are aimed at improving function of
      specific fingers or the thumb, the RIHM (Rotterdam Intrinsic Hand Myometer) is a
      validated tool and offers more detailed information to assess strength of the
      involved joints besides grip and pinch measurements. METHODS: In this study,
      strength was measured in 65 thumbs in 40 patients diagnosed with thumb
      hypoplasia. These 65 thumbs were classified according to Blauth. Longitudinal
      radial deficiencies were also classified. The strength measurements comprised of
      grip, tip, tripod and key pinch. Furthermore palmar abduction and opposition of
      the thumb as well as abduction of the index and little finger were measured with
      the RIHM. FINDINGS: For all longitudinal radial deficiency patients, grip and
      pinch strength as well as palmar abduction and thumb opposition were
      significantly lower than reference values (P<0.001). However, strength in the
      index finger abduction and the little finger abduction was maintained or
      decreased to a lesser extent according to the degree of longitudinal radial
      deficiency. All strength values decreased with increasing Blauth-type. Blauth
      type II hands (n=15) with flexor digitorum superficialis 4 opposition transfer
      including stabilization of the metacarpophalangeal joint showed a trend toward a
      higher opposition strength without reaching statistical significance
      (P=0.094),however compared to non-operated Blauth-type II hands (n=6) they showed
      a lower grip strength (P=0.019). INTERPRETATION: The RIHM is comparable in
      accuracy to other strength dynamometers. Using the RIHM, we were able to
      illustrate strength patterns on finger-specific level, showing added value when
      evaluating outcome in patients with hand related problems.

PMID- 23948240
TI  - A new strategy for methylated DNA detection based on photoelectrochemical
      immunosensor using Bi2S3 nanorods, methyl bonding domain protein and anti-his tag
      antibody.
AB  - In this work, we fabricated a novel photoelectrochemical immunosensor for assay
      of DNA methylation, where Bi2S3 nanorods were used as photoelectric conversion
      material, MBD1 protein (a kind of methyl bonding domain protein) was used as DNA
      methylation recognizing unit, anti-his tag antibody was used to further inhibit
      the photocurrent and increase the detection sensitivity. The results demonstrated
      that Bi2S3 possessed excellent photoelectron property. The detection conditions,
      such as Bi2S3 concentration, MBD1 protein concentration, incubation time of MBD1
      protein, antibody concentration and antibody incubation time, were optimized.
      Under optimal experimental conditions, the photocurrent variation was
      proportional to the logarithm of methylated target DNA concentration from 10(-9)
      to 10(-13) M with detection limit of 3.5*10(-14) M (S/N=3). Moreover, the
      immunosensor presented high detection specificity, even distinguishing single
      base mismatched sequence.

PMID- 23948241
TI  - High density microarrays on Blu-ray discs for massive screening.
AB  - The potential and the capabilities of Blu-ray technology (discs and drives) for
      massive screening applications are presented. High density microarrays are
      fabricated onto a Blu-ray disc and applied for the determination of microcystin
      residues and pathogenic microorganisms. Specific probes were physisorbed onto the
      BD surface and the biorecognition event was displayed using labeled secondary
      antibody solution and subsequent signal amplification. The attenuation of the
      reflected light caused by the reaction product is detected by the Blu-ray drive
      and inversely correlated with analyte concentration. BDs preserve the optical
      properties according to Blu-ray specifications, ensuring maximum accuracy and
      sensitivity of the drive during disc scanning. Detection limits of 0.4 MUg/L for
      microcystin LR and 10(0) and 10(1) cfu/mL for Salmonella typhimurium and
      Cronobacter sakazakii respectively, were achieved, improving considerably the DVD
      performances and reaching similar sensitivity as real-time quantitative PCR. Blu
      ray technology adapted to the analysis of high density arrays highlights the
      enormous capabilities (high sensitivity, speed-scanning, optical resolution,
      portability) for point-of-care settings, diagnostics, and high-throughput
      screening applications.

PMID- 23948242
TI  - Colorimetric detection of controlled assembly and disassembly of aptamers on
      unmodified gold nanoparticles.
AB  - Aptamers are nucleic acid ligands that are generated artificially by in vitro
      selection and behave similar to antibodies. The development of aptamer-based
      sensing systems or strategies has been in vogue for the past few decades, because
      aptamers are smaller in size, stable, cheaper and undergo easier modifications.
      Owing to these advantages, several facile aptamer-based colorimetric strategies
      have been created by controlling the assembly and disassembly of aptamers on
      unmodified gold nanoparticle probes. As these kinds of assay systems are rapid
      and can be visualized unaided by instruments, they have recently become an
      attractive method of choice. The formation of purple-colored aggregates
      (attraction) from the red dispersed (repulsion) state of GNPs in the presence of
      mono- or divalent ions is the key principle behind this assay. Due to its
      simplicity and versatility, this assay can be an alternative to existing
      diagnostic assays. Here, we have investigated the critical elements involved in
      colorimetric assays, and have screened different proteins and small ligands to
      evaluate biofouling on GNPs. 

PMID- 23948243
TI  - Surface stress-based biosensors.
AB  - Surface stress-based biosensors, as one kind of label-free biosensors, have
      attracted lots of attention in the process of information gathering and
      measurement for the biological, chemical and medical application with the
      development of technology and society. This kind of biosensors offers many
      advantages such as short response time (less than milliseconds) and a typical
      sensitivity at nanogram, picoliter, femtojoule and attomolar level. Furthermore,
      it simplifies sample preparation and testing procedures. In this work, progress
      made towards the use of surface stress-based biosensors for achieving better
      performance is critically reviewed, including our recent achievement, the
      optimally circular membrane-based biosensors and biosensor array. The further
      scientific and technological challenges in this field are also summarized.
      Critical remark and future steps towards the ultimate surface stress-based
      biosensors are addressed. 

PMID- 23948244
TI  - Interference-free determination of ischemia-modified albumin using quantum dot
      coupled X-ray fluorescence spectroscopy.
AB  - Ischemia-modified protein (IMA) is the most sensitive diagnostic biomarker of
      ischemic heart disease, but differentiation of IMA from human serum albumin
      (HSA), a ubiquitous serum protein, is still challenging owing to the shared
      antigenicity. In this investigation, we developed a rapid and interference-free
      approach for IMA determination using quantum dots-coupled X-ray Fluorescence
      Spectroscopy (Q-XRF). In a typical Q-XRF assay, serum total HSA is quantified
      using quantum dot-coupled sandwich immunoassay, and intact HSA (iHSA) is
      determined using a XRF spectroscopy, by measuring XRF intensity of Co (II) bonded
      to iHSA. IMA concentration is automatically determined within 30 min by
      calculating the difference between total HSA and iHSA. This strategy can
      effectively eliminate the interference from native HSA level. Results show that
      no significant influences have been observed from hemolysis or high levels of
      cholesterol (7 mg/L), triglyceride (5.2 mg/L), IgG (10 g/L), and fibrinogen (4
      g/L). A linearity of 1-100mg/mL is obtained in iHSA determination using XRF
      (r(2)=0.979). The proposed Q-XRF assay demonstrates a lowest detection limit of
      0.05 U/mL. Receiver-operating characteristic (ROC) curves reveal that Q-XRF assay
      provide an improved sensitivity than ACB assay (95.9% vs. 82.9%) in
      differentiating ischemic patients from health individuals, at an optimal cutoff
      point of 79.2U/mL. The proposed approach provides a new strategy for interference
      free, simple and rapid evaluation of IMA concentration by combining sandwich
      immunoassay and XRF spectroscopy.

PMID- 23948245
TI  - Modified carbon paste sensor for the potentiometric determination of neostigmine
      bromide in pharmaceutical formulations, human plasma and urine.
AB  - A novel, simple, rapid, selective and sensitive method for the determination of
      neostigmine (Ns) ion in its bulk powder, different pharmaceutical dosage forms,
      and biological fluids (plasma and urine) using four modified carbon paste
      electrodes was developed. Sensor 1 is based on ion-association Ns-TPB, sensor 2
      used Ns-PT, sensor 3 comprises a mixture of (Ns-PT+Ns-TPB) and sensor 4 was
      constructed using (Ns-PT+beta-CD). Solvent mediator 2-NPPE exhibited a proper
      behavior including Nernstian slope ranging from 61.5+/-0.5 to 64.5+/-0.5 mV per
      decade over the pH range of 3.8-10 for the four sensors. Linear responses of Ns
      within the concentration range 1.0*10(-7)-1.0*10(-2) mol/L were obtained. The
      response time is very short (<=10s) with a detection limit 6.3*10(-8) M. In flow
      injection analysis (FIA), sensor 3 shows a Nernstian slope value 75.5+/-0.5 mV
      per decade within the concentration range of 1*10(-6)-1*10(-2) mol/L and with a
      detection limit 7.5*10(-7) mol/L. The utility of mixed or additives of beta-CD
      had a significant influence on increasing the sensitivity of sensors 3 and 4
      compared to sensors 1 and 2. The sensors were applied for the determination of
      neostigmine (Ns) ion in its bulk powder, different pharmaceutical dosage forms,
      and biological fluids (plasma and urine). The results obtained were satisfactory
      with excellent percentage recovery comparable with official method for the assay
      based on non-aqueous titration using perchloric acid as a titrant.

PMID- 23948246
TI  - The effect of external ankle support on knee and ankle joint movement and loading
      in netball players.
AB  - OBJECTIVES: External ankle support has been successfully used to prevent ankle
      sprains. However, some recent studies have indicated that reducing ankle range of
      motion can place larger loads on the knee. The aim of this study was to
      investigate the effect of external ankle support (braces and high-top shoes) on
      the ankle and knee joint loading during a netball specific landing task. DESIGN:
      A repeated measure design. METHODS: High performance netball players with no
      previously diagnosed severe ankle or knee injury (n=11) were recruited from NSW
      Institute of Sport netball programme. The kinematic and kinetic data were
      collected simultaneously using a 3-D Motion Analysis System and one Kistler force
      plate to measure ground reaction forces. Players performed a single leg landing
      whilst receiving a pass while wearing a standard netball shoe, the same shoe with
      a lace-up brace and a high-top shoe. RESULTS: Only the brace condition
      significantly reduced the ankle range of motion in the frontal plane
      (in/eversion) by 3.95 +/- 3.74 degrees compared to the standard condition. No
      changes were found for the knee joint loading in the brace condition. The high
      top shoes acted to increase the peak knee internal rotation moment by 15%. Both
      the brace and high-top conditions brought about increases in the peak ankle
      plantar flexion moment during the landing phase. CONCLUSIONS: Lace-up braces can
      be used by netball players to restrict ankle range of motion during a single leg
      landing while receiving a pass without increasing the load on the knee joint.

PMID- 23948247
TI  - Evaluation of cardiorespiratory fitness using three field tests in obese
      adolescents: validity, sensitivity and prediction of peak VO2.
AB  - OBJECTIVES: Evaluation of cardiorespiratory fitness in obese adolescents is
      necessary to develop personalised retraining programmes. We aimed to measure
      cardiorespiratory fitness using 3 field tests, and to evaluate their validity and
      sensitivity compared to values obtained by laboratory tests. DESIGN: Longitudinal
      interventional study in obese adolescents admitted to a rehabilitation centre for
      a 9-month programme of obesity management. METHODS: A 12-min walk/run test, an
      adapted 20 m shuttle walk-run test (starting speed 4 km h(-1), increments of 0.5
      km h(-1)min(-1)) and a 4-level submaximal cycle ergometer test were performed to
      estimate respectively distance covered in 12 min, maximum speed and maximal
      aerobic power. RESULTS: Thirty adolescents aged 14.2 +/- 1.6 years were included.
      After 9 months intervention, we observed a significant reduction in body mass
      index, and an increase in peak VO2 and field test results. We observed
      significant correlations between pre- and post-intervention values of peak VO2
      and distance covered in 12 min (r=0.70 pre; r=0.82 post), maximum speed (r=0.80
      pre; r=0.83 post) and maximal aerobic power (r=0.71 pre; r=0.84 post). Multiple
      linear regression made it possible to estimate peak VO2 based on results from the
      3 field tests using prediction equations specific to a population of obese
      adolescents. CONCLUSIONS: These field tests, including the adapted 20 m shuttle
      walk-run test, adequately assess cardiorespiratory fitness in obese adolescents,
      and are sensitive to changes over time. Predictive equations including BMI are
      useful in clinical practice to predict peak VO2 in these patients.

PMID- 23948248
TI  - Structure activity relationship studies of 17-cyclopropylmethyl-3,14beta
      dihydroxy-4,5alpha-epoxy-6alpha-(isoquinoline-3'-carboxamido)morphinan (NAQ)
      analogues as potent opioid receptor ligands: preliminary results on the role of
      electronic characteristics for affinity and function.
AB  - 17-Cyclopropylmethyl-3,14beta-dihydroxy-4,5alpha-epoxy-6alpha-(isoquinoline-3'
      carboxamido)morphinan (NAQ) was previously designed following the 'message
      address' concept and was identified as a potent and highly selective mu opioid
      receptor (MOR) ligand based on its pharmacological profile. We here report the
      preliminary structure activity relationship (SAR) studies of this novel lead
      compound. For the new ligands synthesized as NAQ analogues, their binding assay
      results showed that a longer spacer and a saturated ring system of the side chain
      were unfavorable for their MOR selectivity over the kappa and delta opioid
      receptors. In contrast, substitutions with different electronic properties at
      either 1'- or 4'-position of the isoquinoline ring of the side chain were
      generally acceptable for reasonable MOR selectivity. The majority of NAQ
      analogues retained low efficacy at the MOR compared to NAQ in the (35)S
      GTP[gammaS] binding assays while electron-withdrawing groups at 1'-position of
      the isoquinoline ring induced higher MOR stimulation than electron-donating
      groups did. In summary, the electronic characteristics of substituents at 1'- or
      4'-position of the isoquinoline ring in NAQ seem to be critical and need to be
      further tuned up to achieve higher MOR selectivity and lower MOR stimulation. 

PMID- 23948249
TI  - Highlights of recent developments and trends in cancer nanotechnology research-
      view from NCI Alliance for Nanotechnology in Cancer.
AB  - Although the incidence of cancer and cancer related deaths in the United States
      has decreased over the past two decades due to improvements in early detection
      and treatment, cancer still is responsible for a quarter of the deaths in this
      country. There is much room for improvement on the standard treatments currently
      available and the National Cancer Institute (NCI) has recognized the potential
      for nanotechnology and nanomaterials in this area. The NCI Alliance for
      Nanotechnology in Cancer was formed in 2004 to support multidisciplinary
      researchers in the application of nanotechnology to cancer diagnosis and
      treatment. The researchers in the Alliance have been productive in generating
      innovative solutions to some of the central issues of cancer treatment including
      how to detect tumors earlier, how to target cancer cells specifically, and how to
      improve the therapeutic index of existing chemotherapies and radiotherapy
      treatments. Highly creative ideas are being pursued where novelty in nanomaterial
      development enables new modalities of detection or therapy. This review
      highlights some of the innovative materials approaches being pursued by
      researchers funded by the NCI Alliance. Their discoveries to improve the
      functionality of nanoparticles for medical applications includes the generation
      of new platforms, improvements in the manufacturing of nanoparticles and
      determining the underlying reasons for the movement of nanoparticles in the
      blood. 

PMID- 23948250
TI  - PREEParing for mitosis.
AB  - Reporting in Developmental Cell, Schlaitz et al. (2013) show that endoplasmic
      reticulum (ER) membrane exclusion from the mitotic spindle is an active process
      requiring REEP membrane proteins. REEP protein depletion results in ER membrane
      retention on the spindle and chromosomes, leading to defects in chromosome
      segregation and nuclear envelope assembly.

PMID- 23948251
TI  - CHD5 is required for neurogenesis and has a dual role in facilitating gene
      expression and polycomb gene repression.
AB  - The chromatin remodeler CHD5 is expressed in neural tissue and is frequently
      deleted in aggressive neuroblastoma. Very little is known about the function of
      CHD5 in the nervous system or its mechanism of action. Here we report that
      depletion of Chd5 in the developing neocortex blocks neuronal differentiation and
      leads to an accumulation of undifferentiated progenitors. CHD5 binds a large
      cohort of genes and is required for facilitating the activation of neuronal
      genes. It also binds a cohort of Polycomb targets and is required for the
      maintenance of H3K27me3 on these genes. Interestingly, the chromodomains of CHD5
      directly bind H3K27me3 and are required for neuronal differentiation. In the
      absence of CHD5, a subgroup of Polycomb-repressed genes becomes aberrantly
      expressed. These findings provide insights into the regulatory role of CHD5
      during neurogenesis and suggest how inactivation of this candidate tumor
      suppressor might contribute to neuroblastoma.

PMID- 23948252
TI  - Aurora B and cyclin B have opposite effects on the timing of cytokinesis
      abscission in Drosophila germ cells and in vertebrate somatic cells.
AB  - Abscission is the last step of cytokinesis that physically separates the
      cytoplasm of sister cells. As the final stage of cell division, abscission is
      poorly characterized during animal development. Here, we show that Aurora B and
      Survivin regulate the number of germ cells in each Drosophila egg chamber by
      inhibiting abscission during differentiation. This inhibition is mediated by an
      Aurora B-dependent phosphorylation of Cyclin B, as a phosphomimic form of Cyclin
      B rescues premature abscission caused by a loss of function of Aurora B. We show
      that Cyclin B localizes at the cytokinesis bridge, where it promotes abscission.
      We propose that mutual inhibitions between Aurora B and Cyclin B regulate the
      duration of abscission and thereby the number of sister cells in each cyst.
      Finally, we show that inhibitions of Aurora B and Cyclin-dependent kinase 1
      activity in vertebrate cells also have opposite effects on the timing of
      abscission, suggesting a possible conservation of these mechanisms. 

PMID- 23948255
TI  - Changes in maternal serum insulin-like growth factor-I during pregnancy and its
      relationship to maternal anthropometry.
AB  - BACKGROUND: Insulin-like growth factor (IGF)-I is primarily produced by the liver
      under the stimulation of growth hormone, and has systemic growth effects.
      Placental growth hormone in maternal circulation increases from early pregnancy
      and is responsible for the increment in maternal serum IGF-I. The purpose of this
      study was to evaluate the changes in maternal serum IGF-I during pregnancy and
      their relationship to maternal anthropometry, including body weight (BW) and body
      mass index (BMI). METHODS: We obtained 332 blood samples from 114 expectant
      mothers at different gestational ages (Gas) without adverse medical history.
      Serum IGF-I levels were measured by immunoradiometric assay. Linear regression
      analysis for continuous variables and t test for comparisons of categorical
      variables were used to test for significance. RESULTS: Maternal serum IGF-I
      during pregnancy was significantly correlated not only to GA (p < 0.001, r =
      0.358), but also to maternal BW (p = 0.001, r = 0.202), and maternal BMI (p <
      0.001, r = 0.263). The mean maternal IGF-I was highest in the third trimester
      [1st vs. 2nd, p < 0.001, 95% confidence interval (CI) = -70.17 to -28.22; 1st vs.
      3rd, p < 0.001, 95% CI = -138.02 to -76.94; 1st vs. 3rd, p < 0.001, 95% CI = 
      88.86 to -27.71]. CONCLUSION: Maternal serum IGF-I is significantly related to
      GA, maternal BW, and BMI during pregnancy.

PMID- 23948253
TI  - Exo70 generates membrane curvature for morphogenesis and cell migration.
AB  - Dynamic shape changes of the plasma membrane are fundamental to many processes,
      ranging from morphogenesis and cell migration to phagocytosis and viral
      propagation. Here, we demonstrate that Exo70, a component of the exocyst complex,
      induces tubular membrane invaginations toward the lumen of synthetic vesicles in
      vitro and generates protrusions on the surface of cells. Biochemical analyses
      using Exo70 mutants and independent molecular dynamics simulations based on Exo70
      structure demonstrate that Exo70 generates negative membrane curvature through an
      oligomerization-based mechanism. In cells, the membrane-deformation function of
      Exo70 is required for protrusion formation and directional cell migration. Exo70
      thus represents a membrane-bending protein that may couple actin dynamics and
      plasma membrane remodeling for morphogenesis.

PMID- 23948256
TI  - Comparative study of non-invasive monitoring via infrared spectroscopy for
      mammalian cell cultivations.
AB  - Process analytical technology (PAT) is a guide to improve process development in
      biotech industry. Optical sensors such as near and mid infrared spectrometers
      fulfill an essential part for PAT. NIRS and MIRS were investigated as non
      invasive on line monitoring tools for animal cell cultivations in order to
      predict critical process parameters, like cell parameters as well as substrate
      and metabolite concentrations. Eight cultivations were performed with frequent
      sampling. Variances between cultivations were induced by spiking experiments with
      intent to break correlations between analytes; to keep causality of the models;
      and to increase model robustness. Calibration models were built for each analyte
      using partial least-squares regression method. Cultivations chosen for validation
      were not part of the calibration set. Glucose concentration, cell density and
      viability were predicted by NIRS with a root mean square error of prediction
      (RMSEP) of 0.36 g/L, 3.9 10(6)cells/mL and 3.62% respectively. Based on MIR
      spectra glucose and lactate concentrations were predicted with a RMSEP of 0.16
      and 0.14 g/L respectively. Results show that MIRS has higher accuracy regarding
      the prediction of single analytes. For prediction of a main course of a
      cultivation, NIRS is much better suited than MIRS.

PMID- 23948254
TI  - Oskar is targeted for degradation by the sequential action of Par-1, GSK-3, and
      the SCF-Slimb ubiquitin ligase.
AB  - Translation of oskar messenger RNA (mRNA) is activated at the posterior of the
      Drosophila oocyte, producing Long Oskar, which anchors the RNA, and Short Oskar,
      which nucleates the pole plasm, containing the posterior and germline
      determinants. Here, we show that Oskar is phosphorylated by Par-1 and GSK
      3/Shaggy to create a phosphodegron that recruits the SCF(-Slimb) ubiquitin
      ligase, which targets Short Oskar for degradation. Phosphorylation site mutations
      cause Oskar overaccumulation, leading to an increase in pole cell number and
      embryonic patterning defects. Furthermore, the nonphosphorylatable mutant
      produces bicaudal embryos when oskar mRNA is mislocalized. Thus, the Par-1/GSK
      3/Slimb pathway plays important roles in limiting the amount of pole plasm
      posteriorly and in degrading any mislocalized Oskar that results from leaky
      translational repression. These results reveal that Par-1 controls the timing of
      pole plasm assembly by promoting the localization of oskar mRNA but inhibiting
      the accumulation of Short Oskar protein.

PMID- 23948257
TI  - The secretome of Trametes versicolor grown on tomato juice medium and
      purification of the secreted oxidoreductases including a versatile peroxidase.
AB  - The present work was carried out with the aim to analyze the secretome of
      Trametes versicolor BAFC 2234 grown on tomato juice medium supplemented with
      copper and manganese. T. versicolor BAFC 2234 was selected among diverse wood
      dwelling agaricomycetes from Argentina by its ability to cause a strong white rot
      on hardwood and in addition to show high tolerance toward phenolic compounds. A
      considerable number of the identified proteins were related to the
      degradation/modification of lignocelluloses. Hydrolases, peroxidases and
      phenoloxidases were the most abundant enzymes produced under the above-mentioned
      culture conditions. The lignin-modifying oxidoreductases laccase, manganese
      peroxidase (MnP) and versatile peroxidase (VP) were successfully purified - the
      latter for the first time from T. versicolor. The native VP protein has a
      molecular mass of 45kDa and an isoelectric point of pH 3.7. The study clearly
      shows that complex plant-based media being rich in phenolics, such as tomato
      juice, can stimulate the secretion of a broad set of extracellular
      lignocellulolytic enzymes. Using such natural products as fungal culture media
      may give the opportunity to investigate plant biomass decomposition as well as
      the biodegradation of organic pollutants in an environment close to nature. 

PMID- 23948258
TI  - Biotransformation of dihydroisosteviol and the effects of transformed products on
      steroidogenic gene expressions.
AB  - The biotransformation of dihydroisosteviol with Absidia pseudocylindrospora ATCC
      24169, Streptomyces griseus ATCC 10137, Mucor recurvatus MR36, and Aspergillus
      niger BCRC 31130 yielded 15 metabolites, eight of which were previously unknown.
      Structures of metabolites were established by 2D NMR techniques and HRMS data,
      two of which were further corroborated by chemical means, and another via single
      crystal X-ray diffraction analysis. Subsequently, two steroidogenic cell lines (Y
      1 mouse adrenal tumor and MA-10 mouse Leydig tumor cells) were used in a reverse
      transcription-PCR analysis to assess the effects of all compounds on
      steroidogenic gene expressions using forskolin as a positive control. The tested
      gene expressions included steroidogenic factor-1 (SF-1), steroidogenic acute
      regulatory protein (StAR), and cytochrome P450 side-chain cleavage (P450scc)
      enzyme. Gene expression profiles showed that ten of the tested compounds
      effectively suppressed P450SCC mRNA expression in both Y-1 and MA-10 cells.
      Several induced SF-1 gene expression and two enhanced StAR gene expression in Y-1
      cells. By contrast, in MA-10 cells, one compound effectively suppressed StAR mRNA
      expression, whereas for others effectively suppressed SF-1 gene expression. The
      results suggest that analogs of dihydroisosteviol can be potential modulators to
      alter steroidogenic gene expressions and subsequent enzyme activities. 

PMID- 23948259
TI  - Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae,
      Asteraceae): distribution, (13)C NMR spectral data and biological properties.
AB  - Asteraceae Bercht. & J. Presl is one of the biggest and most economically
      important plant families. The taxonomy and phylogeny of Asteraceae is rather
      complex and according to the latest and most reliable taxonomic classification of
      Panero & Funk, based on the analysis of nine chloroplast regions, the family is
      divided into 12 subfamilies and 35 tribes. One of the largest tribes of
      Asteraceae is Cardueae Cass. with four subtribes (Carlininae, Echinopinae,
      Carduinae and Centaureinae) and more than 2500 species. Susanna & Garcia-Jacas
      have organized the genera of Centaureinae (about 800 species) into seven informal
      groups, which recent molecular studies have confirmed: 1. Basal genera; 2.
      Volutaria group; 3. Rhaponticum group; 4. Serratula group; 5. Carthamus group; 6.
      Crocodylium group; 7. Centaurea group. This review summarizes reports on
      sesquiterpenoids from the Centaureinae subtribe of the Asteraceae family, as well
      as the (13)C NMR spectral data described in the literature. It further reviews
      studies concerning the biological activities of these metabolites. For this work,
      literature data on sesquiterpenes from the Centaureinae subtribe were retrieved
      with the help of the SciFinder database and other similar data banks. All entries
      from 1958 until the end of 2011 were considered. This review is addressed to
      scientists working in the metabolomics field such as chemists, botanists, etc.,
      the spectroscopic data reported make this work a good tool for structural
      elucidation, the biological section gives useful information to those who wish to
      study the structure activity relationships. 

PMID- 23948260
TI  - Spontaneous bleeding from liver after open heart surgery.
AB  - INTRODUCTION: Intra-abdominal hemorrhage after open heart surgery is very
      uncommon in routine clinical practice. There are case reports of having bleeding
      from spleen or liver after starting low molecular weight heparin (LMWH)
      postoperatively. PRESENTATION OF CASE: Our patient is a 58-year-old man with
      mitral valve regurgitation, who underwent mitral valve repair and developed intra
      abdominal hemorrhage 8h after open heart surgery. The exploratory laparotomy
      revealed the source of bleeding from ruptured sub-capsular liver hematoma and
      oozing from raw areas of the liver surface. Liver packing was done to control the
      bleeding. DISCUSSION: The gastrointestinal complications after open heart surgery
      are rare and spontaneous bleeding from spleen has been reported. This is the
      first case from our hospital to have intra-abdominal hemorrhage after open heart
      surgery. CONCLUSION: Spontaneous bleeding from liver is a possible complication
      after open heart surgery. We submit the case for the academic interest and to
      discuss the possible cause of hemorrhage.

PMID- 23948261
TI  - Comparison of three labeled silica nanoparticles used as tracers in transport
      experiments in porous media. Part I: syntheses and characterizations.
AB  - The synthesis and the characterization of three kinds of labeled silica
      nanoparticles were performed. Three different labeling strategies were
      investigated: fluorescent organic molecule (FITC) embedded in silica matrix,
      heavy metal core (Ag(0)) and radioactive core ((110m)Ag) surrounded by a silica
      shell. The main properties and the suitability of each kind of labeled
      nanoparticle in terms of size, surface properties, stability, detection limits,
      and cost were determined and compared regarding its use for transport studies.
      Fluorescent labeling was found the most convenient and the cheapest, but the best
      detection limits were reached with chemical (Ag(0)) and radio-labeled ((110m)Ag)
      nanoparticles, which also allowed nondestructive quantifications. This work
      showed that the choice of labeled nanoparticles as surrogates of natural colloids
      or manufactured nanoparticles strongly depends on the experimental conditions,
      especially the concentration and amount required, the composition of the
      effluent, and the timescale of the experiment.

PMID- 23948262
TI  - Reply to comment on "Characterising metal build-up on urban road surfaces" by .
      Environmental Pollution, 176, 87-91.

PMID- 23948263
TI  - 3,5-Diiodo-l-thyronine induces SREBP-1 proteolytic cleavage block and apoptosis
      in human hepatoma (Hepg2) cells.
AB  - Thyroid hormone 3,5,3'-triiodo-l-thyronine (T3) is known to affect cell
      metabolism through both the genomic and non-genomic actions. Recently, we
      demonstrated in HepG2 cells that T3 controls the expression of SREBP-1, a
      transcription factor involved in the regulation of lipogenic genes. This occurs
      by activation of a cap-independent translation mechanism of its mRNA. Such a
      process is dependent on non-genomic activation of both MAPK/ERK and PI3K/Akt
      pathways. The physiological role of 3,5-diiodo-l-thyronine (T2), previously
      considered only as a T3 catabolite, is of growing interest. Evidences have been
      reported that T2 rapidly affects some metabolic pathways through non-genomic
      mechanisms. Here, we show that T2, unlike T3, determines the block of proteolytic
      cleavage of SREBP-1 in HepG2 cells, without affecting its expression at the
      transcriptional or translational level. Consequently, Fatty Acid Synthase
      expression is reduced. T2 effects depend on the concurrent activation of MAPKs
      ERK and p38, of Akt and PKC-delta pathways. Upon the activation of these signals,
      apoptosis of HepG2 cells seems to occur, starting at 12h of T2 treatment. PKC
      delta appears to act as a switch between p38 activation and Akt suppression,
      suggesting that this PKC may function as a controller in the balance of pro
      apoptotic (p38) and anti-apoptotic (Akt) signals in HepG2 cells. 

PMID- 23948264
TI  - Pathological roles of ceramide and its metabolites in metabolic syndrome and
      Alzheimer's disease.
AB  - The public health burden of metabolic syndrome (MetS), a multiplex risk factor
      that arises from insulin resistance accompanying abnormal adipose conditions, and
      Alzheimer's disease (AD), the most common form of dementia, continues to expand.
      Current available therapies for these disorders are of limited effectiveness.
      Recent findings have indicated that alternations in sphingolipid metabolism
      contribute to the development of these pathologies. Sphingolipids are major
      constituents of the plasma membrane, where they are known to form several types
      of microdomains, and are potent regulators for a variety of physiological
      processes. Many groups, including ours, have demonstrated that membrane
      sphingolipids, especially ceramide and its metabolites such as ceramide 1
      phosphate, have roles in arteriosclerosis, obesity, diabetes, and inflammation
      associated with MetS. Aberrant sphingolipid profiles have been observed in human
      AD brains, and accumulated evidence has demonstrated that changes in membrane
      properties induced by defective sphingolipid metabolism impair generation and
      degradation of amyloid-beta peptide (Abeta), a pathogenic agent of AD. In this
      review, we summarize current knowledge and pathophysiological implications of the
      roles of SLs in MetS and AD, to provide insight into the SL metabolic pathways as
      potential targets for therapy of these diseases. This article is part of a
      Special Issue entitled New Frontiers in Sphingolipid Biology. 

PMID- 23948265
TI  - Enzymatic hydrolysis, adsorption, and recycling during hydrolysis of bagasse
      sulfite pulp.
AB  - The high costs of enzymatic hydrolysis along with the high enzyme dosage are
      often considered as the major bottlenecks in lignocellulosic bioconversion. This
      study investigated the hydrolysis efficiency, cellulase adsorption and enzyme
      recycling during the hydrolysis of bagasse sulfite pulp (BSP). After 48 h of
      hydrolysis, more than 70% of the cellulose was hydrolyzed, while the protein
      concentration and cellulase activity in solution remained 31% and 17% of the
      initial value, respectively. The cellulase adsorption on the fresh BSP was better
      fitted by a Sips model, suggesting the occurrence of a multilayer adsorption at
      low cellulase concentration and monolayer adsorption at high concentration on the
      BSP surfaces. Desorption profile studies showed that the optimum desorption
      condition was at pH 4.8 and 40  degrees C. Moreover, considering the limited
      ability to desorption, directly empolying the bound enzyme with residual
      substrate is more effective method to recover cellulase during the hydrolysis of
      BSP.

PMID- 23948266
TI  - Transformation and removal of wood extractives from pulp mill sludge using wet
      oxidation and thermal hydrolysis.
AB  - In order to remove wood extractive compounds from pulp mill sludge and thereby
      enhancing anaerobic digestibility, samples were subjected to either oxidative
      hydrothermal treatment (wet oxidation) or non-oxidative hydrothermal treatment
      (thermal hydrolysis). Treatments were carried out at 220  degrees C with initial
      pressure of 20 bar. More than 90% destruction of extractive compounds was
      observed after 20 min of wet oxidation. Wet oxidation eliminated 95.7% of
      phenolics, 98.6% fatty acids, 99.8% resin acids and 100% of phytosterols in 120
      min. Acetic acid concentration increased by approximately 2 g/l after 120 min of
      wet oxidation. This has potential for rendering sludge more amenable to anaerobic
      digestion. In contrast thermal hydrolysis was found to be ineffective in
      degrading extractive compounds. Wet oxidation is considered to be an effective
      process for removal of recalcitrant and inhibitive compounds through hydrothermal
      pre-treatment of pulp mill sludge.

PMID- 23948267
TI  - Enhancement of lipid productivity of Rhodosporidium toruloides in distillery
      wastewater by increasing cell density.
AB  - This study is to improve the process of producing lipid convertible to biodiesel,
      from distillery wastewater while simultaneously removing organics and nutrients
      efficiently by inoculating oleaginous yeast Rhodosporidium toruloides in the
      presence of indigenous microorganisms. The lipid productivity of R. toruloides
      was studied using real wastewater obtained from distillery and local municipal
      wastewater treatment plants. Under the conditions of mix rate of 1:1 with
      domestic wastewater, initial soluble chemical oxygen demand (SCOD) over 20,000
      mg/L and initial cell density of 2*10(7) cells/mL at 30  degrees C, lipid content
      and lipid yield achieved were 43.65+/-1.74% and 3.54+/-0.04 g/L, with the
      associated removal efficiencies for COD, total nitrogen (TN), and total
      phosphorus (TP), 86.11+/-0.41%, 57.81+/-0.29%, and 67.69+/-0.73%, respectively,
      after three days of cultivation in real distillery wastewater without pH
      adjustment. The pH of wastewater increased from 3.71 to over 8 in 7 days of
      cultivation.

PMID- 23948268
TI  - Triacylglycerol profiling of microalgae Chlamydomonas reinhardtii and
      Nannochloropsis oceanica.
AB  - Triacylglycerols (TAGs) from microalgae can serve as feedstock for the production
      of biofuels. To gain a comprehensive understanding of TAG metabolism in algae
      through genetic and molecular approaches, and to improve algal biofuel
      production, efficient and quantitative phenotyping methods focusing on TAGs are
      required. Towards this end, a facile ultrahigh performance liquid chromatography
      mass spectrometry protocol was developed for TAG profiling, achieving
      identification and quantification of intact TAG molecular species in two algae.
      TAG profiling was performed in Chlamydomonas reinhardtii and Nannochloropsis
      oceanica grown in nitrogen (N)-replete or N-depleted medium. For the
      quantification of algal TAGs and fatty acids, two sets of internal standards were
      developed by taking advantage of the presence of pheophytin and specific fatty
      acids in algal samples. Comparison of algal TAG levels was simplified by using
      these internal standards for TAG analysis, paving the way for high-throughput
      mutant screening. 

PMID- 23948269
TI  - Hydrogen and methane production by co-digestion of waste activated sludge and
      food waste in the two-stage fermentation process: substrate conversion and energy
      yield.
AB  - Batch experiments were conducted to produce hydrogen and methane from waste
      activated sludge and food waste by two-stage mesophilic fermentation. Hydrogen
      and methane production, energy yield, soluble organic matters, volatile solid
      removal efficiency and carbon footprint were investigated during two-stage
      digestion at various food waste proportions. The highest energy yield reached
      14.0 kJ/g-VS at the food waste proportion of 85%, with hydrogen and methane
      yields of 106.4 ml-H2/g-VS and 353.5 ml-CH4/g-VS respectively. The dominant VFA
      composition was butyrate for co-digestion and sole food waste fermentation,
      whereas acetate was dominate in VFA for sole waste activated sludge fermentation.
      The VS removal efficiencies of co-digestion were 10-77% higher than that of waste
      activated sludge fermentation. Only 0.1-3.2% of the COD in feedstock was
      converted into hydrogen, and 14.1-40.9% to methane, with the highest value of
      40.9% in methane achieved at food waste proportion of 85%.

PMID- 23948270
TI  - Catalytic pyrolysis of sugarcane bagasse by using microwave heating.
AB  - The aim of this study was to research the catalytic effects on the microwave
      pyrolysis of sugarcane bagasse and thus to discuss the reaction performance,
      product distribution, and kinetic analysis. With the addition of metal-oxides
      served as catalysts, reaction results such as mass reduction ratio and reaction
      rate increased, even the maximum temperature decreased. Adding either NiO or CaO
      slightly increased the production of H2, while adding either CuO or MgO slightly
      decreased it. The addition of either CaO or MgO enhanced the gaseous production,
      and either NiO or CuO addition enhanced the liquid production. There could be
      several secondary reactions such as self-gasification and interactions among the
      gases originally produced during the pyrolysis stage to alter the composition of
      gaseous product and the final three-phase product distribution. The catalyst
      addition slightly increased the activation energy but greatly increased the pre
      exponential factor. 

PMID- 23948271
TI  - Disintegration of aerobic granules: role of second messenger cyclic di-GMP.
AB  - Loss of structural stability of aerobic granular process is the challenge for its
      field applications to treat wastewaters. The second messenger, cyclic diguanylate
      (c-di-GMP), is widely used by bacteria to regulate the synthesis of
      exopolysaccharide. This study for the first time confirmed the correlation
      between concentration of intracellular c-di-GMP and the granular stability under
      sequencing batch reactor (MBR) mode. In the presence of manganese ions (Mn(2+)),
      the concentrations of intracellular c-di-GMP and of extracellular polysaccharides
      and proteins in granules were declined. Clone library study revealed that the
      polysaccharide producers. Acinetobacter sp., Thauera sp., Bdellovibrio sp. and
      Paracoccus sp. were lost after Mn(2+) addition. The findings reported herein
      confirmed that the c-di-GMP is a key chemical factor epistatic to quorum sensing
      to determine granular stability. Stimulation of synthesis of intracellular c-di
      GMP presents a potential way to enhance long-term stability of aerobic granules. 

PMID- 23948272
TI  - Dynamics of microbial communities related to biochemical parameters during
      vermicomposting and maturation of agroindustrial lignocellulose wastes.
AB  - Scarce information is available on the changes in abundance of microbial taxa
      during vermicomposting. Quantitative PCR and DGGE analysis were used to monitor
      variations in the microbial structure, relative abundance of four bacterial
      classes and fungi over the vermicomposting and maturation period of wet olive
      cake (O) and vine shoots (W). Multivariate correlation analysis between microbial
      structure and abundance, earthworm biomass and enzyme activities revealed similar
      and divergent interactions in both processes. Although Eisenia fetida development
      was different, significant correlations were found with beta-glucosidase activity
      and with bacterial and fungal structure. In the vermicomposting period of O and
      W, a decline was found in bacteria (94% and 77%), fungi (93% and 94%), and
      Gammaproteobacteria (56% and 71%) but an increase in Betaproteobacteria and
      Actinobacteria (62-79%). Alphaproteobacteria increased only in O (26%). Despite
      the different initial lignocellulose wastes, the mature vermicomposts were
      similar in microbial and biochemical properties. 

PMID- 23948273
TI  - Influence of ultrasonic pretreatment on the yield of bio-oil prepared by thermo
      chemical conversion of rice husk in hot-compressed water.
AB  - The aim of the current study is to investigate the feasibility of thermo-chemical
      conversion of rice husk in hot-compressed water via ultrasonic pretreatment to
      increase the bio-oil yield. The results show that ultrasonic pretreatment
      remarkably changes the structures of the rice husk, such as enhancing swelling
      and surface area, eroding lignin structure, and resulting in more exposure of the
      cellulose and hemicellulose. The highest bio-oil yield of 42.8% was obtained from
      the thermo-chemical conversion at 300  degrees C and 0 min of the residence time
      for the 1 h pretreated rice husk. GC-MS analysis indicates that the relative
      contents of phenols, 5-Hydroxymethylfurfural, and lactic acid are higher in bio
      oils obtained from the pretreated rice husks than that from the raw rice husk.

PMID- 23948274
TI  - A comparison of thermal behaviors of raw biomass, pyrolytic biochar and their
      blends with lignite.
AB  - In this study, thermal characteristics of raw biomass, corresponding pyrolytic
      biochars and their blends with lignite were investigated. The results showed that
      pyrolytic biochars had better fuel qualities than their parent biomass. In
      comparison to raw biomass, the combustion of the biochars shifted towards higher
      temperature and occurred at continuous temperature zones. The biochar addition in
      lignite increased the reactivities of the blends. Obvious interactions were
      observed between biomass/biochar and lignite and resulted in increased total
      burnout, shortened combustion time and increased maximum weight loss rate,
      indicating increased combustion efficiencies than that of lignite combustion
      alone. Regarding ash-related problems, the tendency to form slagging and fouling
      increased, when pyrolytic biochars were co-combusted with coal. This present
      study demonstrated that the pyrolytic biochars were more suitable than raw
      biomass to be co-combusted with lignite for energy generation in existing coal
      fired power plants. 

PMID- 23948275
TI  - Optimization of pullulanase production in Escherichia coli by regulation of
      process conditions and supplement with natural osmolytes.
AB  - In this study, the effects of temperature, IPTG (Isopropyl beta-D-1
      thiogalactopyranoside) concentration, and osmolytes (proline, K-glutamate, and
      betaine) on cell growth and soluble pullulanase productivity of recombinant
      Escherichia coli were investigated. The yield of soluble pullulanase was found to
      be enhanced with decrease in cultivation temperature, lower IPTG concentration,
      and betaine supplementation in a shake flask. In addition, a modified two-stage
      feeding strategy was proposed and applied in a 3-L fermentor supplied with 20mM
      betaine, which achieved a dry cell weight of 59.3 g L(-1). Through this
      cultivation approach at 25  degrees C, the total soluble activity of pullulanase
      reached 963.9 U mL(-1), which was 8.3-fold higher than that observed without
      addition of betaine at 30  degrees C (115.8 U mL(-1)). The higher expression of
      soluble pullulanase in a scalable semisynthetic medium showed the potential of
      the proposed process for the industrial production of soluble enzyme.

PMID- 23948276
TI  - High lipid productivity of an Ankistrodesmus-Rhizobium artificial consortium.
AB  - Microalgae have great potential as alternative productive platforms for
      sustainable production of bioenergy, food, feed and other commodities. Process
      optimization to realize the claimed potential often comprises strains selection
      and improvement and also developing of more efficient cultivation, harvesting and
      downstream processing technology. In this work we show that inoculation with the
      bacterium Rhizobium strain 10II resulted in increments of up to 30% in
      chlorophyll, biomass and lipids accumulation of the oleaginous microalgae
      Ankistrodesmus sp. strain SP2-15. Inoculated cultures have reached a high lipid
      productivity of up to 112 mg L(-1) d(-1) after optimization. The resulting
      biomass presented significant levels of Omega3 fatty acids including stearidonic
      acid, suggesting potential as an alternative land-based source of essential fatty
      acids.

PMID- 23948277
TI  - Reduced CD147 expression is linked to ERG fusion-positive prostate cancers but
      lacks substantial impact on PSA recurrence in patients treated by radical
      prostatectomy.
AB  - The extracellular matrix metalloproteinase inducer CD147 has been suggested as a
      prognostic marker in prostate cancer. CD147 expression was analyzed by
      immunohistochemistry on a tissue microarray containing 11,152 prostate cancer
      specimens. Results were compared to tumor phenotype, biochemical recurrence, ERG
      status and deletions on PTEN, 3p13, 6q15 and 5q21. CD147 expression was strong in
      benign prostatic glands and often reduced in prostate cancers. CD147
      immunostaining was found in 71.7% of 7628 interpretable cases. CD147 staining was
      considered strong in 34.6%, moderate in 24.3% and weak in 12.8% of cancers while
      28.3% did not show any CD147 reactivity. Reduced CD147 staining was strongly
      associated with both TMPRSS2-ERG-rearrangement and ERG expression (p<0.0001
      each). Within the subgroups of ERG positive and negative cancers, deletions of
      PTEN, 3p13, 6q15 and 5q21 were unrelated to the CD147 expression status.
      Decreased CD147 expression was significantly linked to high preoperative PSA
      values, high Gleason grade, advanced tumor stage (p<0.0001 each), and positive
      lymph node involvement (p=0.0026) in all cancers. There was a marginal, but
      statistically significant, association of reduced CD147 expression with early
      biochemical recurrence (p=0.0296). The significant reduction of CD147 expression
      in ERG positive prostate cancer provides further evidence for marked biological
      differences between "fusion type" and "non-fusion type" prostate cancer. Despite
      a weak association with PSA recurrence, CD147 cannot be considered a relevant
      prognostic biomarker.

PMID- 23948278
TI  - Involvement of the FoxO3a pathway in the ischemia/reperfusion injury of cardiac
      microvascular endothelial cells.
AB  - FoxO3a, a member of the forkhead transcription factors, has been demonstrated to
      be involved in myocardial ischemia/reperfusion (I/R) injury. Cardiac
      microvascular endothelial cells (CMECs) are some of the predominant cells damaged
      immediately after myocardial I/R injury. Despite the importance of injured CMECs
      in an ischemic heart, little is known about the involvement of FoxO3a in
      regulating CMECs injury. Thus, we used rat CMECs following simulated I/R to
      examine FoxO3a activation and signaling in relation to survival, the cell cycle
      and apoptosis in CMECs. We found that Akt negatively regulates activation of the
      FoxO3a pathway by phosphorylating FoxO3a in CMECs as demonstrated with an Akt
      inhibitor and activator. Upon I/R injury, the FoxO3a pathway was significantly
      activated in CMECs, which was accompanied by Akt deactivation. In parallel, the
      I/R of CMECs induced G1-phase arrest through p27(Kip1) up-regulation and
      significant activation of caspase-3. Accordingly, inhibition of the FoxO3a
      pathway by IGF-1, an Akt activator, could significantly block the I/R-enhanced
      activation of p27(Kip1) and caspase-3 in CMECs. Collectively, our results
      indicate that the FoxO3a pathway is involved in the I/R injury of CMECs at least
      in part through the regulation of cell cycle arrest and apoptosis, suggesting
      that the FoxO3a pathway may be a novel therapeutic target that protects against
      microvascular endothelial damage in ischemic hearts.

PMID- 23948279
TI  - In reply to Clinical practice guidelines for treatment of exercise-associated
      hyponatremia.

PMID- 23948280
TI  - Acne severity and the Global Acne Grading System in polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the association between acne, quantified by the Global
      Acne Grading System (GAGS), and abnormal clinical and laboratory markers of
      androgen excess in patients with polycystic ovary syndrome (PCOS). METHODS: The
      retrospective study included 133 patients with PCOS. Acne severity was quantified
      with the GAGS score, alopecia was graded with the Ludwig classification, and
      hirsutism was quantified with a modified Ferriman-Gallwey (FG) score. RESULTS:
      The mean GAGS score was significantly greater in younger women, those with a
      lower BMI, and those with a higher FG score. There was no relation between the
      mean GAGS score and waist circumference, waist/hip ratio, androgen hormone levels
      (free testosterone, total testosterone, or dehydroepiandrosterone sulfate), sex
      hormone-binding globulin level, or menstrual irregularity. Alopecia was
      significantly associated with an increased waist/hip ratio; there was no relation
      between alopecia and age, waist circumference, body mass index, FG score,
      androgen hormone levels, or menstrual irregularity. A weak positive correlation
      was observed between the GAGS and FG scores. CONCLUSION: The GAGS may provide
      more precise and comprehensive information about acne severity in obese or
      hirsute patients with PCOS because this grading system includes evaluation of the
      type (comedones, papules, pustules, nodules) and location (anatomic area) of acne
      lesions.

PMID- 23948281
TI  - The expression of histone deacetylase 4 is associated with prednisone poor
      response in childhood acute lymphoblastic leukemia.
AB  - This study aimed at the identification of histone deacetylase (HDAC) isoforms
      relevant for childhood acute lymphoblastic leukemia (ALL). Expression of HDAC1-11
      was determined in 93 primary ALL and eight healthy donor samples. HDAC1, HDAC2
      and HDAC8 showed significantly higher expressions in ALL samples. Correlation
      analysis of HDAC expression with clinicopathological parameters revealed that
      high HDAC1, HDAC2, HDAC4 and HDAC11 levels were significantly associated with
      unfavorable prognostic factors. Particularly, high HDAC4 expression was
      associated with high initial leukocyte count, T cell ALL and prednisone poor
      response. siRNA-mediated inhibition of HDAC4 sensitized a T-ALL cell line to
      etoposide-induced cell death. In conclusion, our data point to HDAC4 as drug
      target in childhood ALL, especially in prednisone poor-responders. 

PMID- 23948282
TI  - The early-career consultation psychiatrist.

PMID- 23948283
TI  - Thinking dirty about surrogates: a case of prolonging life to prove paternity.

PMID- 23948284
TI  - The impact of soluble interleukin-2 receptor as a biomarker of delirium.
AB  - BACKGROUND: Biomarkers might help to predict the emergence of delirium. Advance
      warning of the threats of this condition could potentially reduce significant
      morbidity, mortality, and costs of hospitalizing patients. OBJECTIVE: Our
      prospective study investigates for the first time the impact of soluble
      interleukin-2 receptor (sIL-2R) as a biomarker of delirium after cardiac surgery
      with cardiopulmonary bypass (CPB). METHOD: A total of 34 patients who underwent
      elective cardiac surgery with CPB were enrolled. During the intensive care unit
      (ICU) stay and after discharge from the ICU, the delirious state was evaluated
      daily using the Delirium Rating Scale by Trzepacz. sIL-2R was assayed before CPB,
      24 hours postoperatively, and on the day before discharge. RESULTS: After CPB, 11
      patients (32.4%) developed delirium. A short-term delirious state (less than 1
      day) was observed in 3 patients and a prolonged delirious state in 8 patients.
      During the study period, sIL-2R levels decreased 24 hours postoperatively and
      increased afterward (Friedman test; p < 0.001). As shown by the Spearman rank
      correlation, CPB patients with higher Delirium Rating Scale scores 72 hours, 96
      hours, and 120 hours postoperatively had significant higher sIL-2R levels 24
      hours postoperatively. In CPB patients with a prolonged postoperative delirious
      state, the sIL-2R level is statistically significantly elevated 24 hours
      postoperatively in comparison with CPB patients without a postoperative delirium
      (Mann-Whitney U: 48.5, p = 0.049). CONCLUSION: High levels of sIL-2R appear to be
      a useful biomarker to identify patients with high risk for a delirious state.

PMID- 23948285
TI  - An unusual cause of iatrogenic aortic regurgitation.

PMID- 23948287
TI  - Phrenic nerve injury during cardiac surgery: mechanisms, management and
      prevention.
AB  - Phrenic nerve injury is a well-recognised complication of cardiac surgery that
      can lead to disabling effects from diaphragmatic dysfunction, especially in
      children and patients with a history of chronic obstructive airway disease.
      Various mechanisms of injury have been recognised including hypothermia,
      mechanical trauma and possibly ischaemia. A clear understanding of these
      mechanisms is important in order to modify surgical techniques to prevent this
      serious complication of cardiac surgery.

PMID- 23948286
TI  - Low high-density lipoprotein cholesterol is not a risk factor for recurrent
      vascular events in patients with vascular disease on intensive lipid-lowering
      medication.
AB  - OBJECTIVES: This study sought to evaluate the vascular risk of low high-density
      lipoprotein-cholesterol (HDL-C) in relation to the use and intensity of lipid
      lowering medication in patients with clinically manifest vascular diseases.
      BACKGROUND: Low levels of HDL-C are associated with an increased risk for
      vascular diseases and may contribute to residual vascular risk in patients
      already treated for other risk factors. However, post-hoc analyses from statin
      trials indicate that the vascular risk associated with low HDL-C may be low or
      even absent in patients using intensive statin therapy. METHODS: We performed a
      prospective cohort study of 6,111 patients with manifest vascular disease. Cox
      proportional hazards models were used to evaluate the risk of HDL-C on vascular
      events in patients using no, usual dose, or intensive lipid-lowering therapy.
      RESULTS: New vascular events (myocardial infarction, stroke, or vascular death)
      occurred in 874 subjects during a median follow-up of 5.4 years (interquartile
      range: 2.9 to 8.6 years). In patients not using lipid-lowering medication at
      baseline (n = 2,153), a 0.1 mmol/l increase in HDL-C was associated with a 5%
      reduced risk for all vascular events (hazard ratio [HR]: 0.95; 95% confidence
      interval [CI]: 0.92 to 0.99). In patients on usual dose lipid-lowering medication
      (n = 1,910) there was a 6% reduced risk (HR: 0.94; 95% CI: 0.90 to 0.98).
      However, in patients using intensive lipid-lowering treatment (n = 2,046), HDL-C
      was not associated with recurrent vascular events (HR: 1.02; 95% CI: 0.98 to
      1.07) irrespective of low-density lipoprotein cholesterol level. CONCLUSIONS: In
      patients with clinically manifest vascular disease using no or usual dose lipid
      lowering medication, low plasma HDL-C levels are related to increased vascular
      risk, whereas in patients using intensive lipid-lowering medication, HDL-C levels
      are not related to vascular risk.

PMID- 23948288
TI  - The 'down-under repair' for ischaemic mitral regurgitation.
AB  - Current surgical management of restrictive ischaemic mitral regurgitation (IMR)
      includes mitral valve annuloplasty (MVA) using an undersized ring when the
      mechanism is secondary to leaflet restriction. In our experience, MVA alone is
      inadequate to eliminate mitral incompetence in these patients. We report the
      'Down-Under Repair' as an adjunctive concept for the treatment of a subset of
      patients with restrictive IMR and associated inferobasal left ventricular
      aneurysm. The 'Down-Under Repair' reduces mitral leaflet restriction by
      approximating the origin of the posterior papillary muscle towards the mitral
      annulus. Midterm results demonstrated sustained valvular competence and
      symptomatic improvement. 

PMID- 23948289
TI  - Notch 1 signalling inhibits cardiomyocyte apoptosis in ischaemic
      postconditioning.
AB  - AIM: Recent studies have demonstrated that Notch signalling pathway is an
      important mediator of cardiac repair and regeneration after myocardial
      infarction. However, the mechanism by which Notch signalling pathway is mediating
      cardioprotection after ischaemic postconditioning (IPost) is still not understood
      thoroughly. The aim of the present study was to investigate the mechanism by
      which Notch signalling pathway mediated the cardioprotection effect after IPost.
      METHODS: Rat heart-derived H9c2 cells were randomly divided into six groups as
      follows: Control group, hypoxia/reoxygenation group (H/R), H/R+N1ICD group, H
      post group, H-post+Notch-1miRNA group, and Mock group. We used pcDNA3.1-Myc-His
      plasmid and RNA interference (RNAi) to activate/inhibit the expression of Notch-1
      in H9c2 cell lines. The Bcl-2, Bax genes and proteins were assessed by
      quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and
      Western blot analysis. The effects of Notch 1 signalling on cell survival,
      proliferation and apoptosis were detected by 3-(4,5)-dimethylthiahiazo (-z-y1)
      3,5-di-phenytetrazoliumromide (MTT) and flow cytometry analysis, respectively.
      Furthermore, Notch 1 signalling induced the disruption of mitochondrial membrane
      potential, thus leading to the activation of caspase-9/-3 measured using the
      colorimetric activity assay. RESULTS: We found Notch 1 signalling reduced
      cardiomyocyte apoptosis in IPost through regulating the expression of Bcl-2, Bax
      and activation of caspase-9 and -3. We found that after transfected with pcDNA3.1
      Myc-His plasmid, activation of the Notch 1 gene effectively promoted cell
      proliferation and inhibited apoptosis. The Notch 1 upregulation was accompanied
      by an upregulation of Bcl-2 and a downregulation of Bax. In addition, a paralled
      increase in caspase-9/-3 activities was observed. These effects were blunted by
      transfected with Notch-1 miRNA in the H9c2 cells. CONCLUSION: Notch 1 signalling
      has a cardioprotection effect, which may result from cardiomyocyte apoptosis, by
      means of regulating the expression of cell apoptosis inhibiting proteins Bcl-2,
      Bax and the activation of caspase-9 and -3.

PMID- 23948290
TI  - Unusual case of acute posteromedial papillary muscle rupture after acute anterior
      myocardial infarction.
AB  - Papillary muscle rupture is now a rare complication of acute myocardial
      infarction. Posteromedial papillary muscle rupture is more common than
      anterolateral papillary muscle rupture. The posteromedial papillary muscle is
      usually supplied from a branch of the right coronary artery. We present a case of
      posteromedial papillary muscle rupture due to an isolated left anterior
      descending artery lesion. This was diagnosed on the fifth day post infarction.
      The patient progressed to mitral valve replacement and coronary artery bypass
      grafting to the left anterior descending artery. We believe this unusual arterial
      supply to the posteromedial papillary muscle is due to an apex forming left
      anterior descending artery coupled with an apically located posteromedial
      papillary muscle. 

PMID- 23948291
TI  - Epilepsy surgery in children with accompanying impairments.
AB  - The aim of this study was to assess seizure outcome 2 years after epilepsy
      surgery in a consecutive series of paediatric patients, with special focus on
      children with learning disabilities and other neuroimpairments in addition to the
      epilepsy. Outcome 2 years after surgery was assessed in 110 of 125 children
      operated upon for drug resistant epilepsy in Gothenburg 1987-2006. More than half
      of the children had learning disabilities, 43% motor impairments and 30% a
      neuropsychiatric diagnosis. Fifty-six per cent of those with an IQ < 70 became
      seizure-free or had a >75% reduction in seizure frequency, and two thirds if the
      operation was a resection. The corresponding figure in those with more than 100
      seizures per month was 15 out of 31, and another seven had a 50-75% reduction in
      seizure frequency. The message is that learning disability, motor impairment and
      psychiatric morbidity should not be contraindications for paediatric epilepsy
      surgery. More than half of the children with learning disabilities had a
      worthwhile seizure outcome, with even better results after resective surgery.
      Children with drug resistant epilepsy and additional severe neurological
      impairments should have the benefit of referral to a tertiary centre for
      evaluation for epilepsy surgery.

PMID- 23948292
TI  - Emerging from NF-kappaB's shadow, SUMOylated IkappaBalpha represses
      transcription.
AB  - In this issue of Cancer Cell, Mulero and colleagues describe an NF-kappaB
      independent transcriptional repression function for SUMOylated IkappaBalpha. This
      compelling and provocative model links IkappaBalpha to the activity of the
      Polycomb repressors and provides a mechanism to link inflammatory signaling to
      skin homeostasis. 

PMID- 23948293
TI  - The kinase-independent, second life of CDK6 in transcription.
AB  - CDK6 is an oncogenic kinase regulating the cell cycle. In this issue of Cancer
      Cell, Kollmann and colleagues demonstrate that CDK6 performs a kinase-independent
      transcriptional function in regulating expression of VEGF-A and p16INK4a. These
      observations link the cell cycle machinery and angiogenesis and reveal the
      presence of a fail-safe antiproliferative mechanism.

PMID- 23948294
TI  - The origins of tumor-promoting inflammation.
AB  - Inflammation is increasingly recognized as an essential component of tumor
      development, but the origin of tumor-associated inflammation remains largely
      unknown. In this issue of Cancer Cell, Pribluda and colleagues find that chronic
      stress initiates senescence-inflammatory response, which can promote
      tumorigenesis in the absence of exogenous inflammatory triggers.

PMID- 23948295
TI  - IL-11: a prominent pro-tumorigenic member of the IL-6 family.
AB  - Cytokines have recently emerged as important players in tumor promotion and
      progression. In this issue of Cancer Cell, Putoczki and colleagues report the
      importance of interleukin 11 in a variety of gastrointestinal malignances and lay
      down a framework for its potential inhibition in a variety of human cancers.

PMID- 23948296
TI  - HSF1 in Translation.
AB  - The master regulator of the classical cytoprotective "heat shock" response, heat
      shock factor 1 (HSF1), is increasingly implicated in cancer pathogenesis, but the
      mechanisms remain poorly understood. A recent study connects increased protein
      translation to activation of HSF1 in malignant cells and demonstrates the
      therapeutic benefit of targeting this link. 

PMID- 23948298
TI  - A genome-wide siRNA screen identifies proteasome addiction as a vulnerability of
      basal-like triple-negative breast cancer cells.
AB  - Basal-like triple-negative breast cancers (TNBCs) have poor prognosis. To
      identify basal-like TNBC dependencies, a genome-wide siRNA lethality screen
      compared two human breast epithelial cell lines transformed with the same genes:
      basal-like BPLER and myoepithelial HMLER. Expression of the screen's 154 BPLER
      dependency genes correlated with poor prognosis in breast, but not lung or colon,
      cancer. Proteasome genes were overrepresented hits. Basal-like TNBC lines were
      selectively sensitive to proteasome inhibitor drugs relative to normal
      epithelial, luminal, and mesenchymal TNBC lines. Proteasome inhibition reduced
      growth of established basal-like TNBC tumors in mice and blocked tumor-initiating
      cell function and macrometastasis. Proteasome addiction in basal-like TNBCs was
      mediated by NOXA and linked to MCL-1 dependence.

PMID- 23948297
TI  - A kinase-independent function of CDK6 links the cell cycle to tumor angiogenesis.
AB  - In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at
      high levels in lymphoid malignancies. In a model for p185BCR-ABL+ B-acute
      lymphoid leukemia, we show that CDK6 is part of a transcription complex that
      induces the expression of the tumor suppressor p16INK4a and the pro-angiogenic
      factor VEGF-A. This function is independent of CDK6's kinase activity. High CDK6
      expression thus suppresses proliferation by upregulating p16INK4a, providing an
      internal safeguard. However, in the absence of p16INK4a, CDK6 can exert its full
      tumor-promoting function by enhancing proliferation and stimulating angiogenesis.
      The finding that CDK6 connects cell-cycle progression to angiogenesis confirms
      CDK6's central role in hematopoietic malignancies and could underlie the
      selection pressure to upregulate CDK6 and silence p16INK4a.

PMID- 23948299
TI  - Amplification of distant estrogen response elements deregulates target genes
      associated with tamoxifen resistance in breast cancer.
AB  - A causal role of gene amplification in tumorigenesis is well known, whereas
      amplification of DNA regulatory elements as an oncogenic driver remains unclear.
      In this study, we integrated next-generation sequencing approaches to map distant
      estrogen response elements (DEREs) that remotely control the transcription of
      target genes through chromatin proximity. Two densely mapped DERE regions located
      on chromosomes 17q23 and 20q13 were frequently amplified in estrogen receptor
      alpha-positive luminal breast cancer. These aberrantly amplified DEREs
      deregulated target gene expression potentially linked to cancer development and
      tamoxifen resistance. Progressive accumulation of DERE copies was observed in
      normal breast progenitor cells chronically exposed to estrogenic chemicals. These
      findings may extend to other DNA regulatory elements, the amplification of which
      can profoundly alter target transcriptome during tumorigenesis.

PMID- 23948300
TI  - Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal
      tumorigenesis and can be targeted therapeutically.
AB  - Among the cytokines linked to inflammation-associated cancer, interleukin (IL)-6
      drives many of the cancer "hallmarks" through downstream activation of the
      gp130/STAT3 signaling pathway. However, we show that the related cytokine IL-11
      has a stronger correlation with elevated STAT3 activation in human
      gastrointestinal cancers. Using genetic mouse models, we reveal that IL-11 has a
      more prominent role compared to IL-6 during the progression of sporadic and
      inflammation-associated colon and gastric cancers. Accordingly, in these models
      and in human tumor cell line xenograft models, pharmacologic inhibition of IL-11
      signaling alleviated STAT3 activation, suppressed tumor cell proliferation, and
      reduced the invasive capacity and growth of tumors. Our results identify IL-11
      signaling as a potential therapeutic target for the treatment of gastrointestinal
      cancers.

PMID- 23948301
TI  - Sentinel node biopsy versus low axillary sampling in women with clinically node
      negative operable breast cancer.
AB  - BACKGROUND: Sentinel node biopsy (SNB) was initially conceived as excision of the
      first station axillary lymph node(s) (LN) identified by radioactive and/or blue
      dye uptake. The definition was subsequently enlarged to also include palpable
      lymph nodes in the vicinity of sentinel node(s) (SN). We reasoned that the
      excision of this combination of nodes might be best achieved by sampling the
      lower axilla. METHODS: Each patient underwent low axillary sampling (LAS) and
      identification of SN in the excised specimen followed by complete axillary lymph
      node dissection (ALND). LAS was defined as excision of all fibrofatty tissue
      overlying the second digitation of serratus anterior below the intercostobrachial
      nerve and was carried out following a pre-operative injection of radioactive
      colloid and an intra-operative injection of blue dye. Blue and/or hot nodes
      (B&/HN) in the dissected tissue and remaining axilla, along with any palpable
      nodes within the sampled tissue, were defined as SN. The primary endpoint of the
      study was to compare false negative rates (FNR) of SN with that of LAS in
      predicting axillary LN status (NCT00128362). FINDINGS: The study was performed
      between March 2004 and December 2011 in 478 women with clinically node negative
      axilla. On histopathological evaluation the median tumor size was 2.5 cm and
      axillary nodal metastases were found in 34.1% of patients. The FNR of SNB (12.7%,
      95% CI 8.1-19.4) and LAS (10.5%, 95% CI 6.6-16.2) were not significantly
      different (p = 0.56). The FNR of B&/HN alone, without palpable nodes, (29.0%, 95%
      CI 22.5-36.6) was significantly inferior to those of SNB (p = 0.0007) and LAS (p
      = 0.0003). INTERPRETATION: LAS is as accurate as SNB in predicting axillary LN
      status in women with clinically node negative operable breast cancer. Confining
      SNB procedure to excision of B&/HN, significantly increases the risk of leaving
      behind metastatic lymph nodes in the axilla. LAS is an effective and low cost
      procedure that minimizes axillary surgery and can be implemented widely. Registry
      Name: Clinicaltrials.gov. REGISTRATION NUMBER: NCT00128362.

PMID- 23948302
TI  - STAT3-mediated attenuation of CCl4-induced mouse liver fibrosis by the protein
      kinase inhibitor sorafenib.
AB  - There have been major advances in defining the immunological events associated
      with fibrosis in various chronic liver diseases. We have taken advantage of this
      data to focus on the mechanisms of action of a unique multi-kinase inhibitor,
      coined sorafenib, on CCl4-induced murine liver fibrosis, including the effects of
      this agent in models of both acute and chronic CCl4-mediated pathology.
      Importantly, sorafenib significantly attenuated chronic liver injury and
      fibrosis, including reduction in liver inflammation and histopathology as well as
      decreased expression of liver fibrosis-related genes, including alpha-smooth
      muscle actin, collagen, matrix metalloproteinases and the tissue inhibitor of
      metalloproteinase-1. Furthermore, sorafenib treatment resulted in translocation
      of cytoplasmic STAT3 to the nucleus in its active form. Based on this
      observation, we used hepatocyte-specific STAT3 knockout (STAT3(Hep-/-)) mice to
      demonstrate that hepatic STAT3 was critical for sorafenib-mediated protection
      against liver fibrosis, and that the upregulation of STAT3 phosphorylation was
      dependent on Kupffer cell-derived IL-6. In conclusion, these data reflect the
      clinical potential of the multi-kinase inhibitor sorafenib for the prevention of
      fibrosis as well as the treatment of established liver fibrosis and illustrate
      the immunological mechanisms that underlie the protective effects of sorafenib. 

PMID- 23948303
TI  - AKT activation drives the nuclear localization of CSE1L and a pro-oncogenic
      transcriptional activation in ovarian cancer cells.
AB  - The human homolog of the yeast cse1 gene (CSE1L) is over-expressed in ovarian
      cancer. CSE1L forms complex with Ran and importin-alpha and has roles in
      nucleocytoplasmic traffic and gene expression. CSE1L accumulated in the nucleus
      of ovarian cancer cell lines, while it was localized also in the cytoplasm of
      other cancer cell lines. Nuclear localization depended on AKT, which was
      constitutively active in ovarian cancer cells, as the CSE1L protein translocated
      to the cytoplasm when AKT was inactivated. Moreover, the expression of a
      constitutively active AKT forced the translocation of CSE1L from the cytoplasm to
      the nucleus in other cancer cells. Nuclear accrual of CSE1L was associated to the
      nuclear accumulation of the phosphorylated Ran Binding protein 3 (RanBP3), which
      depended on AKT as well. Also in samples of human ovarian cancer, AKT activation
      was associated to nuclear accumulation of CSE1L and phosphorylation of RanBP3.
      Expression profiling of ovarian cancer cells after CSE1L silencing showed that
      CSE1L was required for the expression of genes promoting invasion and metastasis.
      In agreement, CSE1L silencing impaired motility and invasiveness of ovarian
      cancer cells. Altogether these data show that in ovarian cancer cells activated
      AKT by affecting RanBP3 phosphorylation determines the nuclear accumulation of
      CSE1L and likely the nuclear concentration of transcription factors conveying pro
      oncogenic signals.

PMID- 23948304
TI  - Papillomavirus E6 oncoprotein up-regulates occludin and ZO-2 expression in
      ovariectomized mice epidermis.
AB  - We have studied the expression of the tight junction proteins (TJ) occludin,
      claudin-1 and ZO-2 in the epidermis of female mice. We observed a peak of
      expression of these proteins at postnatal day 7 and a decrease in 6 week-old mice
      to values similar to those found in newborn animals. We explored if the
      expression of the E6 oncoprotein from high-risk human papilloma virus type 16
      (HPV16) in the skin of transgenic female mice (K14E6), altered TJ protein
      expression in a manner sensitive to ovarian hormones. We observed that in
      ovariectomized mice E6 up-regulates the expression of occludin and ZO-2 in the
      epidermis and that this effect was canceled by 17beta-estradiol. Progesterone
      instead induced occludin and ZO-2 over-expression. However, the decreased
      expression of occludin and ZO-2 induced by 17beta-estradiol in the epidermis was
      not overturned by E6 or progesterone. In addition, we employed MDCK cells
      transfected with E6, and observed that ZO-2 delocalizes from TJs and accumulates
      in the cell nuclei due to a decrease in the turnover rate of the protein. These
      results reinforce the view of 17beta-estradiol and E6 as risk factors for the
      development of cancer through effects on expression and mislocalization of TJ
      proteins.

PMID- 23948305
TI  - Chronic inflammation-derived nitric oxide causes conversion of human colonic
      adenoma cells into adenocarcinoma cells.
AB  - It has been suggested that nitric oxide (NO) derived from chronically inflamed
      tissues is a cause of carcinogenesis. We herein demonstrated that administration
      of an inducible NO synthase inhibitor, aminoguanidine, significantly suppressed
      the tumorigenic conversion of human colonic adenoma (FPCK-1-1) cells into
      adenocarcinoma (FPCK/Inflam) cells accelerated by foreign body-induced chronic
      inflammation in nude mice. To determine whether NO directly promotes
      carcinogenesis, we exposed FPCK-1-1 cells continuously to chemically generated NO
      (FPCK/NO), and periodically examined their tumorigenicity. FPCK/NO cells formed
      tumors, whereas vehicle-treated cells (FPCK/NaOH) did not. We selected a
      tumorigenic population from FPCK/NO cells kept it in three-dimensional (3D)
      culture where in vivo-like multicellular spheroidal growth was expected.
      FPCK/Inflam cells developed large spheroids whereas FPCK/NO cells formed tiny but
      growing compact aggregates in 3D culture. Meanwhile, FPCK-1-1 and FPCK/NaOH cells
      underwent anoikis (apoptotic cell death consequential on insufficient cell-to
      substrate interactions) through activation of caspase 3. The survived cells in
      the 3D culture (FPCK/NO/3D), which were derived from FPCK/NO cells, showed a
      similar tumor incidence to that of FPCK/Inflam cells. These results showed that
      NO was one of the causative factors for the acceleration of colon carcinogenesis,
      especially in the conversion from adenoma to adenocarcinoma in the chronic
      inflammatory environment. 

PMID- 23948306
TI  - In brown adipocytes, adrenergically induced beta1-/beta3-(Gs)-, alpha2-(Gi)- and
      alpha1-(Gq)-signalling to Erk1/2 activation is not mediated via EGF receptor
      transactivation.
AB  - Brown adipose tissue is unusual in that the neurotransmitter norepinephrine
      influences cell destiny in ways generally associated with effects of classical
      growth factors: regulation of cell proliferation, of apoptosis, and progression
      of differentiation. The norepinephrine effects are mediated through G-protein
      coupled receptors; further mediation of such stimulation to e.g. Erk1/2
      activation is in cell biology in general accepted to occur through
      transactivation of the EGF receptor (by external or internal pathways). We have
      examined here the significance of such transactivation in brown adipocytes.
      Stimulation of mature brown adipocytes with cirazoline (alpha1-adrenoceptor
      coupled via Gq), clonidine (alpha2 via Gi) or CL316243 (beta3 via Gs) or via
      beta1-receptors significantly activated Erk1/2. Pretreatment with the EGF
      receptor kinase inhibitor AG1478 had, remarkably, no significant effect on Erk1/2
      activation induced by any of these adrenergic agonists (although it fully
      abolished EGF-induced Erk1/2 activation), demonstrating absence of EGF receptor
      mediated transactivation. Results with brown preadipocytes (cells in more
      proliferative states) were not qualitatively different. Joint stimulation of all
      adrenoceptors with norepinephrine did not result in synergism on Erk1/2
      activation. AG1478 action on EGF-stimulated Erk1/2 phosphorylation showed a sharp
      concentration-response relationship (IC50 0.3uM); a minor apparent effect of
      AG1478 on norepinephrine-stimulated Erk1/2 phosphorylation showed nonspecific
      kinetics, implying caution in interpretation of partial effects of AG1478 as
      reported in other systems. Transactivation of the EGF receptor is clearly not a
      universal prerequisite for coupling of G-protein coupled receptors to Erk1/2
      signalling cascades.

PMID- 23948307
TI  - Luminescence characteristics of Li2CO3-K2CO3-H3BO3 glasses co-doped with
      TiO2/MgO.
AB  - Understanding the influence of co-dopants in the luminescence enhancement of
      carbonate glasses is the key issue in dosimetry. A series of borate glasses
      modified by lithium and potassium carbonate were synthesized by the melt
      quenching method. The glass mixture activated with various concentrations of TiO2
      and MgO was subjected to various doses of gamma-rays ((60)Co). The amorphous
      nature of the samples was confirmed by x-ray diffraction (XRD) spectra. The
      simple glowing curve of the glass doped with TiO2 features a peak at 230 degrees
      C, whose intensity is maximal at 0.5 mol% of the dopant. The intensity of the
      glowing curve increases with the concentration of MgO added as a co-dopant up to
      0.25 mol%, where it is two times higher than for the material without MgO
      thermoluminescence properties, including dose response, reproducibility, and
      fading were studied. The effective atomic number of the material was also
      determined. Kinetic parameters, such as kinetics order, activation energy, and
      frequency factor are estimated. The photoluminescence spectra of the titanium
      doped glass consist of a prominent peaks at 480 nm when laser excitation at 650
      nm is used. A three-fold photoluminescence enhancement and a blue shift of the
      peak were observed when 0.1% MgO was introduced. In addition, various physical
      parameters, such as ion concentration, polaron radius and internuclear distances
      were calculated. The mechanism for the thermoluminescence and photoluminescence
      enhancements are discussed.

PMID- 23948308
TI  - Reversed phase free ion selective radiotracer extraction (RP-FISRE): a new tool
      to assess the dynamic stabilities of metal (-organic) complexes, for complex half
      lives spanning six orders of magnitude.
AB  - This paper introduces reversed phase free ion selective radiotracer extraction
      (RP-FISRE) as a new tool to assess the stability of metal complexes, as
      illustrated by the assessment of the stability of [(177)Lu]Lu-DOTA-octreotate. To
      this end, the TUDelft-developed FISRE, where the released metal is column
      retained and the complex eluted, was changed into RP-FISRE, where the complex is
      column-retained and the released metal is eluted. This change in the approach
      allows for studies to be performed with high stability complexes. This paper
      presents RP-FISRE, the strength of the radiotracer approach, and the first-ever
      kd data on the release of (177)Lu from [(177)Lu]Lu-DOTA-octreotate.

PMID- 23948310
TI  - Quantitative online isolation of 68Ge from 68Ge/68Ga generator eluates for
      purification and immediate quality control of breakthrough.
AB  - The breakthrough of 68Ge from a 68Ge/68Ga-generator is one of the most sensitive
      parameters in the context of the clinical application of 68Ga
      radiopharmaceuticals. The difficulty in its determination lies in the
      "spectroscopic invisibility" of 68Ge within an excess of 68Ga. The introduced
      method for determining the 68Ge content of the 68Ge/68Ga-generator eluate
      involves the quantitative separation of 68Ga from 68Ge, using a cation-exchanger.
      The eluate contains 68Ga free of 68Ge, which can be determined immediately, i.e.
      prior to the application of the 68Ga-radiopharmaceutical.

PMID- 23948309
TI  - Comparison of the activity measurements in nuclear medicine services in the
      Brazilian northeast region.
AB  - The Northeastern Regional Centre for Nuclear Sciences (CRCN-NE), National Nuclear
      Energy Commission, has organized for the first time in nuclear medicine services
      (NMSs) in the Brazilian northeast region a comparison of activity measurements
      for (99m)Tc, (131)I, (67)Ga, (201)Tl and (57)Co. This tool is widely utilized to
      evaluate not only the accuracy of radionuclide calibrators, but also the
      competence of NMSs to measure the activity of the radiopharmaceuticals and the
      performance of the personnel involved in these measurements. The comparison
      results showed that 90% of the results received from participants are within the
      +/-10% limit established by the Brazilian Norm.

PMID- 23948311
TI  - Modeling of the thermoluminescence mechanisms in ZrO2.
AB  - In this paper, simulations of thermoluminescence experiments are carried out
      using the comprehensive model for thermoluminescence cited in the literature by
      several authors, for both natural and laboratory irradiated aliquots. In the
      present work, we propose a possible, alternative model to explain the
      thermoluminescence (TL) process in zirconium oxide (ZrO2). The model includes
      four trapping states and one recombination center (4T1C model). The aim of the
      present study is to present a model that, by using as guess values the parameters
      obtained by employing the GOK model, fits very well the experimental glow curve.
      It is a goal point that the physical model does not need to resort to the quasi
      equilibrium approximation. The results of these simulations are in general
      qualitative agreement with the experiments and confirm that the proposed model in
      this study presents a good explanation of these phenomena. A linear behavior was
      also observed between the response and dose range from 1*10(9) to 9*10(9)cm(-3). 

PMID- 23948312
TI  - Resilience to childhood maltreatment is associated with increased resting-state
      functional connectivity of the salience network with the lingual gyrus.
AB  - The experience of childhood maltreatment is related to an increased risk of
      developing a variety of psychiatric disorders, as well as a change in the
      structure of the brain. However, not much is known about the neurobiological
      basis of resilience to childhood maltreatment. This study aims to identify
      resting-state functional connectivity (RSFC) patterns specific for resilience to
      childhood maltreatment, focusing on the default mode and salience network and
      networks seeded from the amygdala and left dorsomedial prefrontal cortex. Resting
      state functional MRI scans were obtained in 33 individuals. Seeds in the
      bilateral amygdala, the dorsal anterior cingulate cortex (dACC), the posterior
      cingulate cortex and the left dorsomedial prefrontal cortex were defined and used
      to examine whether resilient individuals differed from vulnerable individuals and
      healthy controls in RSFC with other brain regions. Within the salience network,
      the resilient group was associated with increased RSFC between the left dACC and
      a region containing the bilateral lingual gyrus and the occipital fusiform gyrus
      compared to both the vulnerable group and the healthy controls. In this study, we
      found RSFC patterns specific for resilient individuals. Regions that are
      implicated are related on a functional level to declarative memory and the
      processing of emotional stimuli. 

PMID- 23948313
TI  - Effectiveness of specific factors in community-based intervention for child
      witnesses of interparental violence: a randomized trial.
AB  - A community-based intervention with specific factors for children and parents
      exposed to interparental violence (IPV) was compared with a control intervention
      based on non-specific factors. We hypothesized that participation in an
      intervention with specific factors, focused on IPV, parenting and coping, would
      be associated with better recovery. IPV exposed children and parents were group
      randomized over a specific factors- and control intervention. Baseline, posttest
      and follow-up measurements of 155 parents and children (aged 6-12 years, 55.5%
      boys) were fitted in a multilevel model. Outcomes were parent and teacher
      reported children's internalizing and externalizing problems (CBCL, TRF), child
      self-reported depressive symptoms (CDI) and parent and child reported children's
      post-traumatic stress symptoms (TSCYC, TSCC). Based on intention-to-treat and
      completer analyses, children in the specific factors intervention did not show
      better recovery than children in the control intervention. Children in both
      interventions decreased significantly in parent-reported children's internalizing
      and externalizing problems and post-traumatic stress symptoms. Children reported
      a decrease in their mean level of depressive and post-traumatic stress symptoms.
      Teachers reported a decrease in internalizing problems, but not in externalizing
      problems. No association between time since exposure and level and course of
      symptoms was found. Treatment differentiation was assessed and both programs were
      significantly different on hypothesized effective factors. Higher treatment
      adherence in both programs did not result in a larger difference in recovery. IPV
      exposed children improve over the course and after participating in a community
      based child- and parent program, but specific factors in intervention may not
      carry additional benefits when implemented in community settings. 

PMID- 23948314
TI  - Predicting the decisions of hospital based child protection teams to report to
      child protective services, police and community welfare services.
AB  - This study examines judgments made by hospital-based child protection teams
      (CPTs) when determining if there is reasonable suspicion that a child has been
      maltreated, and whether to report the case to a community welfare agency, to
      child protective services (CPS) and/or to the police. A prospective multi-center
      study of all 968 consecutive cases referred to CPTs during 2010-2011 in six
      medical centers in Israel. Centers were purposefully selected to represent the
      heterogeneity of medical centers in Israel in terms of size, geographical
      location and population characteristics. A structured questionnaire was designed
      to capture relevant information and judgments on each child referred to the team.
      Bivariate associations and multivariate multinomial logistic regressions were
      conducted to predict whether the decisions would be (a) to close the case, (b) to
      refer the case to community welfare services, or (c) to report it to CPS and/or
      the police. Bivariate and multivariate analyses identified a large number of case
      characteristics associated with higher probability of reporting to CPS/police or
      of referral to community welfare services. Case characteristics associated with
      the decisions include socio-demographic (e.g., ethnicity and financial status),
      parental functioning (e.g., mental health), previous contacts with authorities
      and hospital, current referral characteristics (e.g., parental referral vs. child
      referral), physical findings, and suspicious behaviors of child and parent. Most
      of the findings suggest that decisions of CPTs are based on indices that have
      strong support in the professional literature. Existing heterogeneity between
      cases, practitioners and medical centers had an impact on the overall
      predictability of the decision to report. Attending to collaboration between
      hospitals and community agencies is suggested to support learning and quality
      improvement. 

PMID- 23948315
TI  - Nymphal development and lerp construction of Glycaspis sp. (Hemiptera:
      Psylloidea) on Eucalyptus sideroxylon (Myrtaceae) in central-west New South
      Wales, Australia.
AB  - The ability to form lerps is common in Australian Psylloidea. Various species of
      Glycaspis Taylor (Aphalaridae) form conical lerps on different species of
      Eucalyptus. Lerps, being a rich sugar source, are preferentially fed by bell
      miners (Aves: Meliphagidae). In this paper we report the process of lerp
      construction by a purported new species of Glycaspis living on Eucalyptus
      sideroxylon. This taxon constructs lerps with anal sugary exudates first building
      the ribs of the lerps and later filling the space between the polymerized ribs
      with horizontal tractions of the same sugary substance. Developmental events in
      this taxon do not follow Dyar's rule strictly. Oviposition induces a non-lethal
      hypersensitive response in the host leaf. Population trends assessed in 2011-2012
      and 2012-2013 showed distinct variations, which have been related to
      environmental factors. In the 2012-2013 sampling, oviposition occurred
      preferentially proximally to leaf cracks (possibly induced by intense frost
      events); we infer that this could be a strategy of this taxon to establish an
      'easier' access to moisture. Sensillar designs vary between the nymphal instars
      and adults. The trichoid sensilla and sensillar cavities on the antennae perform
      mechanosensory and olfactory functions. The mouthpart complex includes a
      relatively long stylet bundle. 

PMID- 23948316
TI  - Characterization of copy number variation in genomic regions containing STR loci
      using array comparative genomic hybridization.
AB  - Short tandem repeat (STR) loci are commonly used in forensic casework, familial
      analysis for human identification, and for monitoring hematopoietic cell
      engraftment after bone marrow transplant. Unexpected genetic variation leading to
      sequence and length differences in STR loci can complicate STR typing, and
      presents challenges in casework interpretation. Copy number variation (CNV) is a
      relatively recently identified form of genetic variation consisting of genomic
      regions present at variable copy numbers within an individual compared to a
      reference genome. Large scale population studies have demonstrated that likely
      all individuals carry multiple regions with CNV of 1kb in size or greater in
      their genome. To date, no study correlating genomic regions containing STR loci
      with CNV has been conducted. In this study, we analyzed results from 32,850
      samples sent for clinical array comparative genomic hybridization (CGH) analysis
      for the presence of CNV at regions containing the 13 CODIS (Combined DNA Index
      System) STR, and the Amelogenin X (AMELX) and Amelogenin Y (AMELY) loci. Thirty
      two individuals with CNV involving STR loci on chromosomes 2, 4, 7, 11, 12, 13,
      16, and 21, and twelve with CNV involving the AMELX/AMELY loci were identified.
      These results were correlated with data from publicly available databases housing
      information on CNV identified in normal populations and additional clinical
      cases. These collective results demonstrate the presence of CNV in regions
      containing 9 of the 13 CODIS STR and AMELX/Y loci. Further characterization of
      STR profiles within regions of CNV, additional cataloging of these variants in
      multiple populations, and contributing such examples to the public domain will
      provide valuable information for reliable use of these loci. 

PMID- 23948317
TI  - Evaluation of the iPLEX(r) Sample ID Plus Panel designed for the Sequenom
      MassARRAY(r) system. A SNP typing assay developed for human identification and
      sample tracking based on the SNPforID panel.
AB  - Sequenom launched the first commercial SNP typing kit for human identification,
      named the iPLEX((r)) Sample ID Plus Panel. The kit amplifies 47 of the 52 SNPs in
      the SNPforID panel, amelogenin and two Y-chromosome SNPs in one multiplex PCR.
      The SNPs were analyzed by single base extension (SBE) and Matrix Assisted Laser
      Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). In this
      study, we evaluated the accuracy and sensitivity of the iPLEX((r)) Sample ID Plus
      Panel by comparing the typing results of the iPLEX((r)) Sample ID Plus Panel with
      those obtained with our ISO 17025 accredited SNPforID assay. The average call
      rate for duplicate typing of any one SNPs in the panel was 90.0% when the mass
      spectra were analyzed automatically with the MassARRAY((r)) TYPER 4.0 genotyping
      software in real time. Two reproducible inconsistencies were observed (error
      rate: 0.05%) at two different SNP loci. In addition, four inconsistencies were
      observed once. The optimal amount of template DNA in the PCR was >=10ng. There
      was a relatively high risk of allele and locus drop-outs when <=1ng template DNA
      was used. We developed an R script with a stringent set of "forensic analysis
      parameters" based on the peak height and the signal to noise data exported from
      the TYPER 4.0 software. With the forensic analysis parameters, all
      inconsistencies were eliminated in reactions with >=10ng DNA. However, the
      average call rate decreased to 69.9%. The iPLEX((r)) Sample ID Plus Panel was
      tested on 10 degraded samples from forensic case-work. Two samples could not be
      typed, presumably because the samples contained PCR and SBE inhibitors. The
      average call rate was generally lower for degraded DNA samples and the number of
      inconsistencies higher than for pristine DNA. However, none of the
      inconsistencies were reproduced and the highest match probability for the
      degraded samples typed with the panel was 1.7E-9 using the stringent forensic
      analysis parameters. Although the relatively low sensitivity of the iPLEX((r))
      Sample ID Plus Panel makes it inappropriate for typing of trace samples from
      crime scenes, the panel may be interesting for relationship testing and for
      identification of e.g. samples in biobanks because of the low reagent costs, the
      limited hands-on time of the iPLEX((r)) assay and the automatic analysis of the
      mass spectra. 

PMID- 23948318
TI  - A DNA extraction method of small quantities of bone for high-quality genotyping.
AB  - DNA genotyping techniques have been used successfully in forensic science for
      almost three decades and represent the gold standard for individual
      identification. However, efficient protocols for obtaining DNA from exhumed bones
      suitable for genotyping are still scarce and most of them require a considerable
      amount of starting material, are time consuming and are inefficient for reducing
      inhibitor's effects. We sought to develop an optimised protocol for extracting
      DNA from bone samples obtained from exhumations. We tested two approaches for
      preparing bone samples: (a) fine powder and (b) thin slices of bone. The best
      ratio of bone amount to DNA yields was assessed by a titration experiment using
      bone powder ranging from 50 to 1000mg. We obtained optimal DNA yields (27pg mg(
      1) on average) when 150-200mg of starting material were processed using a one
      step demineralisation method. Better-quality profiles (determined by the number
      of genotyped loci) were obtained when DNA was extracted from bone slices compared
      to extraction from bone powder. From bone slices 83.9% and from bone powder 46.7%
      of the samples provided genotypes for 11 or more loci. Since bone preparation
      procedures were carried out at room temperature, the method developed in the
      present study might be an attractive alternative to the standard freeze-mill
      approach, being faster and more cost-efficient.

PMID- 23948319
TI  - Can brothers share the same STR profile?
AB  - This report demonstrates the limits of DNA identification when siblings are
      involved. The Israeli DNA database routinely amplifies suspects samples using the
      PowerPlex((r)) ESI16 system (Promega). While uploading a series of suspects into
      the database software, we found an unusual high number of shared alleles between
      two suspects 31 out of 32 alleles. Verification of their demographic data
      identified them as brothers. After confirmation of their paternity affiliation
      using the AmpFlSTR((r))YFilerTM (Applied Biosystems), we used two other
      multiplexes kits to improve the differentiation rate. The PowerPlex((r)) ESX17
      System (Promega) added one locus, SE33, who exhibits four different alleles. The
      second kit, the AmpFlSTR((r))MiniFilerTM (Applied Biosystems) added three more
      loci. Only one allele difference was found. In order to increase the
      discrimination power between related and unrelated individuals, we recommend that
      the DNA laboratories consider using a larger multiplex typing kit in cases like
      the one informed here. 

PMID- 23948320
TI  - Forensic DNA methylation profiling--potential opportunities and challenges.
AB  - Investigating the DNA sequence is the most powerful tool that can be employed in
      forensic genetics for the identification of an individual, or to determine
      specific ethnic and phenotypic characteristics. However, there are also other
      heritable changes in gene function or cellular phenotype which are caused by
      mechanisms other than differences in the DNA sequence itself. Over the last
      decade it has become evident that epigenetic markers can be of substantial
      forensic significance. The determination of possible alterations in DNA
      methylation patterns could aid various forensic investigations, such as
      differentiating monozygotic twins, identifying the tissue source or determining
      the age of tissue donors. This review aims to give a brief overview of the
      possible advantages of forensic DNA methylation profiling and sheds light on the
      limitations of this approach. 

PMID- 23948321
TI  - Genetic analyses of the human eye colours using a novel objective method for eye
      colour classification.
AB  - In this study, we present a new objective method for measuring the eye colour on
      a continuous scale that allows researchers to associate genetic markers with
      different shades of eye colour. With the use of the custom designed software
      Digital Iris Analysis Tool (DIAT), the iris was automatically identified and
      extracted from high resolution digital images. DIAT was made user friendly with a
      graphical user interface. The software counted the number of blue and brown
      pixels in the iris image and calculated a Pixel Index of the Eye (PIE-score) that
      described the eye colour quantitatively. The PIE-score ranged from -1 to 1 (brown
      to blue). The software eliminated the need for user based interpretation and
      qualitative eye colour categories. In 94% (570) of 605 analyzed eye images, the
      iris region was successfully extracted and a PIE-score was calculated. A very
      high correlation between the PIE-score and the human perception of eye colour was
      observed. The correlations between the PIE-scores and the six IrisPlex SNPs
      (HERC2 rs12913832, OCA2 rs1800407, SLC24A4 rs12896399, TYR rs1393350, SLC45A2
      rs16891982 and IRF4 rs12203592) were analyzed in 570 individuals. Significant
      differences (p<10(-6)) in the PIE-scores of the individuals typed as HERC2
      rs12913832 G (PIE=0.99) and rs12913832 GA (PIE=-0.71) or A (PIE=-0.87) were
      observed. We adjusted for the effect of HERC2 rs12913832 and showed that the
      quantitative PIE-scores were significantly associated with SNPs with minor
      effects (OCA2 rs1800407, SLC24A4 rs12896399 and TYR rs1393350) on the eye colour.
      We evaluated the two published prediction models for eye colour (IrisPlex [1] and
      Snipper[2]) and compared the predictions with the PIE-scores. We found good
      concordance with the prediction from individuals typed as HERC2 rs12913832 G.
      However, both methods had difficulties in categorizing individuals typed as HERC2
      rs12913832 GA because of the large variation in eye colour in HERC2 rs12913832 GA
      individuals. With the use of the DIAT software and the PIE-score, it will be
      possible to automatically compare the iris colour of large numbers of iris images
      obtained by different studies and to perform large meta-studies that may reveal
      loci with small effects on the eye colour. 

PMID- 23948322
TI  - The interpretation of single source and mixed DNA profiles.
AB  - A method for interpreting autosomal mixed DNA profiles based on continuous
      modelling of peak heights is described. MCMC is applied with a model for allelic
      and stutter heights to produce a probability for the data given a specified
      genotype combination. The theory extends to handle any number of contributors and
      replicates, although practical implementation limits analyses to four
      contributors. The probability of the peak data given a genotype combination has
      proven to be a highly intuitive probability that may be assessed subjectively by
      experienced caseworkers. Whilst caseworkers will not assess the probabilities per
      se, they can broadly judge genotypes that fit the observed data well, and those
      that fit relatively less well. These probabilities are used when calculating a
      subsequent likelihood ratio. The method has been trialled on a number of mixed
      DNA profiles constructed from known contributors. The results have been assessed
      against a binary approach and also compared with the subjective judgement of an
      analyst. 

PMID- 23948323
TI  - High resolution mapping of Y haplogroup G in Tyrol (Austria).
AB  - The distribution of Y-chromosomal haplogroup G2a (G-P15) in present-day paternal
      lineages in Tyrol (Austria) was analyzed by applying a high-density regional
      sampling scheme that also covered remote mountain areas. There is evidence from
      ancient genetic data for a high frequency of Y-chromosomal haplogroup G in
      prehistoric populations of Central Europe, whilst nowadays levels well below 10%
      are routinely observed. A population sample comprising ~3700 specimens was
      analyzed for Y-chromosomal variation by genotyping Y-SNPs and Y-STRs. The set of
      binary markers included nine SNPs specific for sub-lineages of haplogroup G. The
      frequency of haplogroup G in 2379 unrelated men born in Tyrol amounted to 11.3%.
      Nearly all of these Y chromosomes belonged to haplogroup G2a. The main sub
      haplogroup within G2a was defined by the SNP L497 (G2a3b1c) and reached a
      population frequency of 8.6%. Although this average level is higher than reported
      for other countries the geographical distribution of haplogroup G-L497 showed a
      differentiated pattern with a clustered distribution within some alpine valleys,
      where maxima above 40% were found. Both, the estimation of coalescent times and a
      principle coordinates analysis based on RST values derived from Y-STR haplotypes
      from different sub-regions of Tyrol revealed evidence for an old settlement
      history associated with Y chromosomes belonging to haplogroup G in the Tyrolean
      Alps. 

PMID- 23948324
TI  - Ancestry analysis reveals a predominant Native American component with moderate
      European admixture in Bolivians.
AB  - We have genotyped 46 Ancestry Informative Markers (AIMs) in two of the most
      populated areas in Bolivia, namely, La Paz (Andean region; n=105), and Chuquisaca
      (Sub-Andean region; n=73). Using different analytical tools, we inferred
      admixture proportions of these two American communities by comparing the genetic
      profiles with those publicly available from the CEPH (Centre d'Etude du
      Polymorphisme Humain) panel representing three main continental groups (Africa,
      Europe, and America). By way of simulations, we first evaluated the minimum
      sample size needed in order to obtain accurate estimates of ancestry proportions.
      The results indicated that sample sizes above 30 individuals could be large
      enough to estimate main continental ancestry proportions using the 46 AIMs panel.
      With the exception of a few individuals, the results also indicated that
      Bolivians showed a predominantly Native American ancestry with variable levels of
      European admixture. The proportions of ancestry were statistically different in
      La Paz and Chuquisaca: the Native American component was 86% and 77% (Mann
      Whitney U-test: un-adjusted P-value=2.1*10(-5)), while the European ancestry was
      13% and 21% (Mann-Whitney U-test: un-adjusted P-value=3.6*10(-5)), respectively.
      The African ancestry in Bolivians captured by the AIMs analyzed in the present
      study was below 2%. The inferred ancestry of Bolivians fits well with previous
      studies undertaken on haplotype data, indicating a major proportion of Native
      American lineages. The genetic differences observed in these two groups suggest
      that forensic genetic analysis should be better performed based on local
      databases built in the main Bolivian areas. 

PMID- 23948326
TI  - Appel Botha: The abc of a three hundred year old divorce case.
AB  - In 1683 Maria Kickers and Jan Cornelitz got married in Cape Town. Today, 330
      years later, the living patrilineal descendants of Maria's four sons, number in
      excess of 76,000 people. Curiously, none of them carry the surname Cornelitz - in
      fact, they are all called Botha and include former President P.W. Botha, general
      Louis Botha and Minister Pik Botha. The reason for this anomaly is also the
      reason why Jan got divorced from Maria in 1700. According to Maria's testimonies
      she did indeed have a long term relationship with Frederik Botha, but in her
      defence she claimed that her husband was impotent and that he actually encouraged
      her. Other witnesses, presumably prompted by Jan, gave testimonies that implied
      that Maria was in fact licentious. We combined haplotyping with the AmpFlSTR((r))
      YfilerTM kit with deep-rooting genealogies to show that Maria's first son was
      actually fathered by Ferdinandus Appel and that roughly half the living Bothas
      (38,000 people) actually descend from Ferdinandus Appel while the remaining three
      sons all stem from the same father, presumably Frederik Botha, and this implies
      that Maria's husband did not father any of her sons. 

PMID- 23948325
TI  - Evaluation of next generation mtGenome sequencing using the Ion Torrent Personal
      Genome Machine (PGM).
AB  - Insights into the human mitochondrial phylogeny have been primarily achieved by
      sequencing full mitochondrial genomes (mtGenomes). In forensic genetics (partial)
      mtGenome information can be used to assign haplotypes to their phylogenetic
      backgrounds, which may, in turn, have characteristic geographic distributions
      that would offer useful information in a forensic case. In addition and perhaps
      even more relevant in the forensic context, haplogroup-specific patterns of
      mutations form the basis for quality control of mtDNA sequences. The current
      method for establishing (partial) mtDNA haplotypes is Sanger-type sequencing
      (STS), which is laborious, time-consuming, and expensive. With the emergence of
      Next Generation Sequencing (NGS) technologies, the body of available mtDNA data
      can potentially be extended much more quickly and cost-efficiently. Customized
      chemistries, laboratory workflows and data analysis packages could support the
      community and increase the utility of mtDNA analysis in forensics. We have
      evaluated the performance of mtGenome sequencing using the Personal Genome
      Machine (PGM) and compared the resulting haplotypes directly with conventional
      Sanger-type sequencing. A total of 64mtGenomes (>1 million bases) were
      established that yielded high concordance with the corresponding STS haplotypes
      (<0.02% differences). About two-thirds of the differences were observed in or
      around homopolymeric sequence stretches. In addition, the sequence alignment
      algorithm employed to align NGS reads played a significant role in the analysis
      of the data and the resulting mtDNA haplotypes. Further development of alignment
      software would be desirable to facilitate the application of NGS in mtDNA
      forensic genetics. 

PMID- 23948327
TI  - Evaluating forensic DNA profiles using peak heights, allowing for multiple
      donors, allelic dropout and stutters.
AB  - Increases in the sensitivity of DNA profiling technology now allow profiles to be
      obtained from smaller and more degraded DNA samples than was previously possible.
      The resulting profiles can be highly informative, but the subjective elements in
      the interpretation make it problematic to achieve the valid and efficient
      evaluation of evidential strength required in criminal cases. The problems arise
      from stochastic phenomena such as "dropout" (absence of an allele in the profile
      that is present in the underlying DNA) and experimental artefacts such as
      "stutter" that can generate peaks of ambiguous allelic status. Currently in the
      UK, evidential strength evaluation uses an approach in which the complex signals
      in the DNA profiles are interpreted in a semi-manual fashion by trained experts
      aided by a set of guidelines, but also relying substantially on professional
      judgment. We introduce a statistical model to calculate likelihood ratios for
      evaluating DNA evidence arising from multiple known and unknown contributors that
      allows for such stochastic phenomena by incorporating peak heights. Efficient use
      of peak heights allows for more crime scene profiles to be reported to courts
      than is currently possible. The model parameters are estimated from experimental
      data incorporating multiple sources of variability in the profiling system. We
      report and analyse experimental results from the SGMPlus system, run at 28
      amplification cycles with no enhancements, currently used in the UK. Our methods
      are readily adapted to other DNA profiling systems provided that the experimental
      data for the parameter estimation is available. 

PMID- 23948328
TI  - Can glenohumeral joint isokinetic strength and range of movement predict injury
      in professional rugby league.
AB  - OBJECTIVE: To isokinetically record shoulder strength scores and range of motion
      in a professional rugby league squad. To prospectively monitor injuries over a
      season looking for associations between measured variables and injury. DESIGN: A
      cohort study design involving prospective screening of risk factors with
      subsequent injury surveillance. SETTING: University Sports Science Laboratory and
      Professional Rugby League Club. PARTICIPANTS: All players participating in the
      clubs reserve team squad for the 2011 season (n = 20). MAIN OUTCOME MEASURES:
      Concentric (Con) and eccentric (Ecc) peak torque values; ratio of Ecc internal
      rotation IR to Con external rotation ER, also known as the dynamic control ratio
      (DCR), shoulder range of IR and ER. RESULTS: Eight players (36%) received a total
      of eleven injuries over the season. There were no statistically significant
      differences between injured and non-injured shoulders. IR range of movement was
      significantly lower in injured versus non-injured groups with left (p = 0.022)
      and right (p = 0.024). Left IR range of movement was predictive of injury using
      binary logistic regression (p = 0.046). No isokinetic strength parameters reached
      statistical significance (p > 0.05) for prediction of injury; however size
      effects were apparent for reduced con IR of the left shoulder and Ecc IR of both
      shoulders. CONCLUSION: Reduced shoulder IR range appears predictive of future
      shoulder injury although caution is drawn due to small participant numbers.
      Injury prevention strategies for rugby league players should include exercises to
      improve shoulder IR and possibly Ecc IR strength.

PMID- 23948329
TI  - The beautiful game.

PMID- 23948330
TI  - Echinometrin: a novel mast cell degranulating peptide from the coelomic liquid of
      Echinometra lucunter sea urchin.
AB  - Echinometra lucunter is an abundant sea urchin found in Brazilian waters.
      Accidents caused by this animal are common and are characterized by the
      penetration of the spines in the skin, which raises an inflammatory reaction
      through mechanical trauma as well as by the presumable action of toxins.
      Additionally, there have been reports of inflammatory reaction after the
      consumption of raw sea urchin eggs. In this work, we have isolated a peptide from
      E. lucunter coelomic fluid that could elicit inflammatory reactions, such as paw
      edema, leukocyte recruitment and diminishment of the pain threshold. This peptide
      was termed Echinometrin. Moreover, the peptide administration was able to produce
      in vivo degranulation of mouse mast cells, in a dose-response manner. The peptide
      was 'de novo' sequenced by mass spectrometry and its synthetic analog could
      reproduce all the observed effects. Sequence alignment indicates that this
      peptide is comprised in vitellogenin, an abundant nutrient protein present in the
      gametogenic cells of sea urchins, making it possible that echinometrin would be a
      cryptide with pro-inflammatory effects. 

PMID- 23948331
TI  - Categorization of gait patterns in adults with cerebral palsy: a clustering
      approach.
AB  - Gait patterns in adults with cerebral palsy have, to our knowledge, never been
      assessed. This contrasts with the large number of studies which have attempted to
      categorize gait patterns in children with cerebral palsy. Several methodological
      approaches have been developed to objectively classify gait patterns in patients
      with central nervous system lesions. These methods enable the identification of
      groups of patients with common underlying clinical problems. One method is
      cluster analysis, a multivariate statistical method which is used to classify an
      entire data set into homogeneous groups or "clusters". The aim of this study was
      to determine, using cluster analysis, the principal gait patterns which can be
      found in adults with cerebral palsy. Data from 3D motion analyses of 44 adults
      with cerebral palsy were included. A hierarchical cluster analysis was used to
      subgroup the different gait patterns based on spatiotemporal and kinematic
      parameters in the sagittal and frontal planes. Five clusters were identified (C1
      C5) among which, 3 subgroups were determined, based on spontaneous gait speed
      (C1/C2: slow, C3/C4: moderate and C5: almost normal). The different clusters were
      related to specific kinematic parameters that can be assessed in routine clinical
      practice. These 5 classifications can be used to follow changes in gait patterns
      throughout growth and aging as well to assess the effects of different treatments
      (physiotherapy, surgery, botulinum toxin, etc.) on gait patterns in adults with
      cerebral palsy. 

PMID- 23948332
TI  - Changes in timing of muscle contractions and running economy with altered stride
      pattern during running.
AB  - Large alterations to the preferred running stride decrease running economy, and
      shorter strides increase leg muscle activity. However, the effect of altered
      strides on the timing of leg muscle activation is not known. The aim of this
      study was to evaluate the impact of moderate alterations to the running stride on
      running economy and the timing of biceps femoris (BF), vastus lateralis (VL) and
      gastrocnemius (GAST) muscle contractions. The preferred stride pattern for eleven
      trained male runners was measured prior to a separate visit where participants
      ran for bouts of 5 min whilst synchronising foot contacts to a metronome signal
      which was tuned to (1) the preferred stride, and (2) frequencies which related to
      +/- 8% and +/- 4% of the preferred stride length. Running economy was measured at
      each stride pattern along with electromyography and three-dimensional kinematics
      to estimate onset and offset of muscle contractions for each muscle. Running
      economy was greatest at the preferred stride length. However, a quadratic fit to
      the data was optimised at a stride which was 2.9% shorter than preferred. Onset
      and offset of BF and VL muscle contractions occurred earlier with shorter than
      preferred strides. We detected no changes to the timing of muscle contractions
      with longer than preferred strides and no changes to GAST muscle contractions.
      The results suggest that runners optimise running economy with a stride length
      that is close to, but shorter than, the preferred stride, and that timing of BF
      and VL muscle contractions change with shorter than preferred strides.

PMID- 23948333
TI  - Kinematic analysis of step ascent among patients with central visual field loss.
AB  - Vision is of paramount importance in regulating adaptive gait. Using three
      dimensional motion analysis, the current study investigated how central visual
      field loss (CFL) affects step ascent. Ten patients with chronic CFL (77 +/- 10
      years) and 13 visual normal participants (72 +/- 6 years) walked up to and
      ascended a single step (of varying height). Movement kinematics assessed the
      period immediately prior to and during step ascent. Compared to visual normal
      participants, patients with CFL exhibited a lower lead foot horizontal crossing
      velocity, increased lead limb swing time and increased head flexion (looking down
      at more immediate areas of the ground/step). They also took longer to initiate
      the step up, transfer weight to the lead foot upon landing on the upper level and
      increased trail limb swing time when negotiating the medium and high step height.
      Increased variability was also shown in a number of dependent measures. Data
      indicate that during step ascent, patients with CFL exhibit a cautious stepping
      strategy when compared to visual normal participants. This cautious strategy
      becomes increasingly evident when negotiating higher step heights, as shown by an
      increased planning time prior to entering the relatively unstable period of
      single support during the step up. The increased variability among CFL patients
      increases their likelihood of experiencing dynamic instability and falling during
      step ascent.

PMID- 23948334
TI  - Maintaining standing balance by handrail grasping.
AB  - Maintaining balance while standing on a moving bus or subway is challenging, and
      falls among passengers are a significant source of morbidity. Standing passengers
      often rely on handrail grasping to resist perturbations to balance. We conducted
      experiments that simulated vehicle starts, to examine how handrail location
      (overhead or shoulder-height), perturbation direction (forward, backward, left or
      right), and perturbation magnitude (1 or 2m/s(2)) affected the biomechanical
      effort (peak centre-of-pressure (COP) excursion and hand force) and muscle
      activations (onset and integrated EMG activity) involved in balance maintenance.
      COP excursions, hand forces and muscle activations were altered in a functional
      manner based on task constraints and perturbation characteristics. Handrail
      position affected normalized values of peak COP and hand force during forward and
      backward, but not sideways perturbations. During backward perturbations, COP
      excursion was greater when grasping overhead than shoulder-height. During forward
      perturbations, hand force was greater when grasping shoulder-height than
      overhead. Biceps activations were earlier during shoulder-height than overhead
      grasping, while tibialis anterior activity was higher during overhead than
      shoulder-height grasping. Our results indicate that, when facing forward or
      backward to the direction of vehicle motion, overhead grasping minimizes hand
      force, while shoulder-height grasping minimizes COP excursion. In contrast,
      grasping with a sideways stance eliminates the effect of handrail location, and
      was associated with equal or lower biomechanical effort. This suggests that, at
      least for vehicle starts, the most reasonable strategy may be to stand sideways
      to the direction of the vehicle movement, and grasp either at shoulder-height or
      overhead. 

PMID- 23948335
TI  - Concept for estimating mitochondrial DNA haplogroups using a maximum likelihood
      approach (EMMA).
AB  - The assignment of haplogroups to mitochondrial DNA haplotypes contributes
      substantial value for quality control, not only in forensic genetics but also in
      population and medical genetics. The availability of Phylotree, a widely accepted
      phylogenetic tree of human mitochondrial DNA lineages, led to the development of
      several (semi-)automated software solutions for haplogrouping. However, currently
      existing haplogrouping tools only make use of haplogroup-defining mutations,
      whereas private mutations (beyond the haplogroup level) can be additionally
      informative allowing for enhanced haplogroup assignment. This is especially
      relevant in the case of (partial) control region sequences, which are mainly used
      in forensics. The present study makes three major contributions toward a more
      reliable, semi-automated estimation of mitochondrial haplogroups. First, a
      quality-controlled database consisting of 14,990 full mtGenomes downloaded from
      GenBank was compiled. Together with Phylotree, these mtGenomes serve as a
      reference database for haplogroup estimates. Second, the concept of fluctuation
      rates, i.e. a maximum likelihood estimation of the stability of mutations based
      on 19,171 full control region haplotypes for which raw lane data is available, is
      presented. Finally, an algorithm for estimating the haplogroup of an mtDNA
      sequence based on the combined database of full mtGenomes and Phylotree, which
      also incorporates the empirically determined fluctuation rates, is brought
      forward. On the basis of examples from the literature and EMPOP, the algorithm is
      not only validated, but both the strength of this approach and its utility for
      quality control of mitochondrial haplotypes is also demonstrated. 

PMID- 23948336
TI  - Adult caregivers in the United States: characteristics and differences in well
      being, by caregiver age and caregiving status.
AB  - We examined the characteristics of adults providing regular care or assistance to
      friends or family members who have health problems, long-term illnesses, or
      disabilities (ie, caregivers). We used data from the 2009 Behavioral Risk Factor
      Surveillance System (BRFSS) to examine caregiver characteristics, by age and
      caregiving status, and compare these characteristics with those of noncaregivers.
      Approximately 24.7% (95% confidence interval, 24.4%-25.0%) of respondents were
      caregivers. Compared with younger caregivers, older caregivers reported more fair
      or poor health and physical distress but more satisfaction with life and lower
      mental distress. Understanding the characteristics of caregivers can help enhance
      strategies that support their role in providing long-term care. 

PMID- 23948337
TI  - Feasibility of using a community-supported agriculture program to improve fruit
      and vegetable inventories and consumption in an underresourced urban community.
AB  - INTRODUCTION: Direct-to-consumer marketing efforts, such as community-supported
      agriculture (CSA), have been proposed as a solution for disparities in fruit and
      vegetable consumption. Evaluations of such efforts have been limited. The
      objective of this study was to test the feasibility of a CSA intervention to
      increase household inventory of fruits and vegetables and fruit and vegetable
      consumption of residents of an underresourced community. METHODS: For this
      randomized, controlled feasibility study, we recruited 50 low-income women with
      children. Intervention (n=25) participants were offered 5 educational sessions
      and a box of fresh produce for 16 weeks; control participants were not offered
      the sessions nor were they included in the produce delivery. We collected data on
      participants' home inventory of fruits and vegetables and on their consumption of
      fruits and vegetables at baseline (May 2012) and postintervention (August and
      September 2012). RESULTS: Of 55 potential participants, 50 were enrolled and 44
      were reached for follow-up. We observed a significant increase in the number of
      foods in the household inventory of fruits and vegetables in the intervention
      group compared with the control group. The intervention group reported greater
      increases in fruit and vegetable consumption; however, these did not reach
      significance. Intervention participants picked up produce 9.2 (standard
      deviation=4.58) of 16 weeks; challenges included transportation and work
      schedules. Most participants (20 of 21) expressed interest in continued
      participation; all stated a willingness to pay $10 per week, and some were
      willing to pay as much as $25 per week. CONCLUSION: CSA is a feasible approach
      for providing fresh fruits and vegetables to an underresourced community. Future
      studies should evaluate the impact of such a program in a larger sample and
      should take additional steps to facilitate participation.

PMID- 23948338
TI  - A binational overview of reproductive health outcomes among US Hispanic and
      Mexican women in the border region.
AB  - INTRODUCTION: The US-Mexico border region has 15 million residents and 300,000
      births annually. Reproductive health concerns have been identified on both sides
      of the border, but comparable information about reproductive health is not
      available. The objective of this study was to compare reproductive health
      indicators among populations in this region. METHODS: We used 2009 US Hispanic
      and Mexican birth certificate data to compare births inside the border region,
      elsewhere within the border states, and in the United States and Mexico overall.
      We examined trends in total fertility and birth rates using birth data from 2000
      through 2009 and intercensal population estimates. RESULTS: Among women in the
      border region, US women had more lifetime births than Mexican women in 2009 (2.69
      births vs 2.15 births) and throughout the decade. Birth rates in the group aged
      15 to 19 years were high in both the US (73.8/1,000) and Mexican (86.7/1,000)
      border regions. Late or no prenatal care was nearly twice as prevalent in the
      border regions as in the nonborder regions of border states. Low birth weight and
      preterm and early-term birth were more prevalent in the US border than in the
      Mexican border region; US border rates were higher and Mexican rates were lower
      than their corresponding nonborder and national rates. We found some variations
      within border states. CONCLUSION: These findings constitute the first population
      based information on the reproductive health of the entire Hispanic US-Mexico
      border population. Evidence of disparities warrants exploration at state and
      local levels. Teen pregnancy and inadequate prenatal care are shared problems in
      US-Mexico border communities and suggest an area for binational cooperation.

PMID- 23948339
TI  - Bringing bike share to a low-income community: lessons learned through community
      engagement, Minneapolis, Minnesota, 2011.
AB  - BACKGROUND: High prevalence of physical inactivity contributes to adverse health
      outcomes. Active transportation (cycling or walking) is associated with better
      health outcomes, and bike-sharing programs can help communities increase use of
      active transportation. COMMUNITY CONTEXT: The Minneapolis Health Department
      funded the Nice Ride Minnesota bike share system to expand to the Near North
      community in Minneapolis, Minnesota. Near North is a diverse, low-income area of
      the city where residents experience health disparities, including disparities in
      physical activity levels. METHODS: The installation of new bike share kiosks in
      Near North resulted in an environmental change to support physical activity.
      Community engagement was conducted pre-intervention only and consisted of focus
      groups, community meetings, and interviews. Postintervention data on bike share
      trips and subscribers were collected to assess intervention effectiveness.
      OUTCOME: Focus group participants offered insights on facilitators and barriers
      to bike share and suggested system improvements. Community engagement efforts
      showed that Near North residents were positive about Nice Ride and wanted to use
      the system; however, the numbers of trips and subscriptions in Near North were
      low. INTERPRETATION: Results show that the first season of the expansion was
      moderately successful in improving outreach efforts and adapting bike share to
      meet the needs of low-income populations. However, environmental change without
      adequate, ongoing community engagement may not be sufficient to result in
      behavior change.

PMID- 23948340
TI  - Iodine biofortification through plant biotechnology.

PMID- 23948341
TI  - Female biased sex-ratio in Schistosoma mansoni after exposure to an allopatric
      intermediate host strain of Biomphalaria glabrata.
AB  - For parasites that require multiple hosts to complete their development, the
      interaction with the intermediate host may have an impact on parasite
      transmission and development in the definitive host. The human parasite
      Schistosoma mansoni needs two different hosts to complete its life cycle: the
      freshwater snail Biomphalaria glabrata (in South America) as intermediate host
      and a human or rodents as final host. To investigate the influence of the host
      environment on life history traits in the absence of selection, we performed
      experimental infections of two B. glabrata strains of different geographic origin
      with the same clonal population of S. mansoni. One B. glabrata strain is the
      sympatric host and the other one the allopatric host. We measured prevalence in
      the snail, the cercarial infectivity, sex-ratio, immunopathology in the final
      host and microsatellite frequencies of individual larvae in three successive
      generations. We show that, even if the parasite population is clonal based on
      neutral markers, S. mansoni keeps the capacity of generating phenotypic
      plasticity and/or variability for different life history traits when confront to
      an unusual environment, in this study the intermediate host. The most dramatic
      change was observed in sex-ratio: in average 1.7 times more female cercariae were
      produced when the parasite developed in an allopatric intermediate host. 

PMID- 23948342
TI  - Lifespan trends of autobiographical remembering: episodicity and search for
      meaning.
AB  - Autobiographical memories of older adults show fewer episodic and more non
      episodic elements than those of younger adults. This semantization effect is
      attributed to a loss of episodic memory ability. However the alternative
      explanation by an increasing proclivity to search for meaning has not been ruled
      out to date. To test whether a decrease in episodicity and an increase in meaning
      making in autobiographical narratives are related across the lifespan, we used
      different instructions, one focussing on specific episodes, the other on
      embedding events in life, in two lifespan samples. A continuous decrease of
      episodic quality of memory (memory specificity, narrative quality) was confirmed.
      An increase of search for meaning (interpretation, life story integration) was
      confirmed only up to middle adulthood. This non-inverse development of
      episodicity and searching for meaning in older age speaks for an autonomous
      semantization effect that is not merely due to an increase in interpretative
      preferences. 

PMID- 23948343
TI  - Turning back the hands of time: autobiographical memories in dementia cued by a
      museum setting.
AB  - The current study examined the effects of cuing autobiographical memory retrieval
      in 12 older participants with dementia through immersion into a historically
      authentic environment that recreated the material and cultural context of the
      participants' youth. Participants conversed in either an everyday setting
      (control condition) or a museum setting furnished in early twentieth century
      style (experimental condition) while being presented with condition matched cues.
      Conversations were coded for memory content based on an adapted version of
      Levine, Svoboda, Hay, Winocur, and Moscovitch (2002) coding scheme. More
      autobiographical memories were recalled in the museum setting, and these memories
      were more elaborated, more spontaneous and included especially more internal
      (episodic) details compared to memories in the control condition. The findings
      have theoretical and practical implications by showing that the memories
      retrieved in the museum setting were both quantitatively and qualitatively
      different from memories retrieved during a control condition. 

PMID- 23948345
TI  - Assessment of a sequential extraction method to evaluate mercury mobility and
      geochemistry in solid environmental samples.
AB  - The development of a sequential extraction method for mercury in solid
      environmental samples is presented. The scheme recognizes and quantifies four
      major phase associations of mercury: "Labile mercury species", "Hg bound to humic
      and fulvic complexes", "elemental Hg and bound to crystalline oxides" and "Hg
      sulfide and refractory species". Model solids were used in this study to evaluate
      different extracting solutions and to determine optimum extraction conditions.
      Sequential and single-step extractions were conducted to evaluate the interaction
      among the successive steps. Different variables such as extractant concentration,
      time, temperature and number of extractions were optimized for each stage when
      necessary. The selectivity of the selected extractions was assured through
      experiments with natural and synthetic matrices of some specific Hg-bearing
      phases. The suitability of the proposed method was evaluated by using four
      certified reference materials from different Hg sources, physicochemical
      properties and total Hg content (from 0.3ugg(-1) to 33ugg(-1)). Recovery of total
      Hg by the sum of fractions in reference materials showed that the accuracy of the
      method ranges from 85 percent to 105 percent. 

PMID- 23948344
TI  - Transmural IK(ATP) heterogeneity as a determinant of activation rate gradient
      during early ventricular fibrillation: mechanistic insights from rabbit
      ventricular models.
AB  - BACKGROUND: Activation rate (AR) gradients develop during ventricular
      fibrillation (VF), with the highest AR on the surface near Purkinje system (PS)
      terminals (endocardium in humans and rabbits and epicardium in pigs). The
      application of glibenclamide to block adenosine triphosphate (ATP)-sensitive
      potassium current (IK(ATP)) before VF induction eliminates transmural AR
      gradients and prevents the induction of sustained arrhythmia. It remains unclear
      whether the PS, which is resistant to ischemia, is also a factor in AR
      heterogeneity. OBJECTIVE: To dissect IK(ATP) and PS contributions to AR gradients
      during VF by using detailed computer simulations. METHODS: We constructed rabbit
      ventricular models with either subendocardial or subepicardial PS terminals.
      Physiologically relevant IK(ATP) gradients were implemented, and early VF was
      induced and observed. RESULTS: Prominent AR gradients were observed only in
      models with large IK(ATP) gradients. The critical underlying factor of AR
      gradient maintenance was refractoriness in low-IK(ATP) regions, which blocked the
      propagation of action potentials from high-IK(ATP) regions. The PS played no role
      in transmural AR gradient maintenance, but did cause local spatial heterogeneity
      of AR on the surface adjacent to terminals. Simulated glibenclamide application
      during VF led to spontaneous arrhythmia termination within a few seconds in most
      cases, which builds on previous experimental findings of anti-VF properties of
      glibenclamide pretreatment. CONCLUSION: Differential IK(ATP) across the
      ventricular wall is an important factor underlying AR gradients during VF; thus,
      higher epicardial AR in pigs is most likely due to an abundance of epicardial
      IK(ATP). For terminating early VF, our results suggest that IK(ATP) modulation is
      a stronger target than Purkinje ablation.

PMID- 23948346
TI  - Is there an own-race preference in attractiveness?
AB  - Even in multicultural nations interracial relationships and marriages are quite
      rare, one reflection of assortative mating. A relatively unexplored factor that
      could explain part of this effect is that people may find members of their own
      racial group more attractive than members of other groups. We tested whether
      there is an own-race preference in attractiveness judgments, and also examined
      the effect of familiarity by comparing the attractiveness ratings given by
      participants of different ancestral and geographic origins to faces of European,
      East Asian and African origin. We did not find a strong own-race bias in
      attractiveness judgments, but neither were the data consistent with familiarity,
      suggesting an important role for other factors determining the patterns of
      assortative mating observed. 

PMID- 23948347
TI  - BEACOPPescalated versus ABVD in advanced Hodgkin's lymphoma.

PMID- 23948348
TI  - Effect of initial treatment strategy on survival of patients with advanced-stage
      Hodgkin's lymphoma: a systematic review and network meta-analysis.
AB  - BACKGROUND: Several treatment strategies are available for adults with advanced
      stage Hodgkin's lymphoma, but studies assessing two alternative standards of care
      increased dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine,
      procarbazine, and prednisone (BEACOPPescalated), and doxorubicin, bleomycin,
      vinblastine, and dacarbazine (ABVD)-were not powered to test differences in
      overall survival. To guide treatment decisions in this population of patients, we
      did a systematic review and network meta-analysis to identify the best initial
      treatment strategy. METHODS: We searched the Cochrane Library, Medline, and
      conference proceedings for randomised controlled trials published between
      January, 1980, and June, 2013, that assessed overall survival in patients with
      advanced-stage Hodgkin's lymphoma given BEACOPPbaseline, BEACOPPescalated,
      BEACOPP variants, ABVD, cyclophosphamide (mechlorethamine), vincristine,
      procarbazine, and prednisone (C[M]OPP), hybrid or alternating chemotherapy
      regimens with ABVD as the backbone (eg, COPP/ABVD, MOPP/ABVD), or doxorubicin,
      vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone
      combined with radiation therapy (the Stanford V regimen). We assessed studies for
      eligibility, extracted data, and assessed their quality. We then pooled the data
      and used a Bayesian random-effects model to combine direct comparisons with
      indirect evidence. We also reconstructed individual patient survival data from
      published Kaplan-Meier curves and did standard random-effects Poisson regression.
      Results are reported relative to ABVD. The primary outcome was overall survival.
      FINDINGS: We screened 2055 records and identified 75 papers covering 14 eligible
      trials that assessed 11 different regimens in 9993 patients, providing 59 651
      patient-years of follow-up. 1189 patients died, and the median follow-up was 5.9
      years (IQR 4.9-6.7). Included studies were of high methodological quality, and
      between-trial heterogeneity was negligible (tau(2)=0.01). Overall survival was
      highest in patients who received six cycles of BEACOPPescalated (HR 0.38, 95%
      credibility interval [CrI] 0.20-0.75). Compared with a 5 year survival of 88% for
      ABVD, the survival benefit for six cycles of BEACOPPescalated is 7% (95% CrI 3
      10)-ie, a 5 year survival of 95%. Reconstructed individual survival data showed
      that, at 5 years, BEACOPPescalated has a 10% (95% CI 3-15) advantage over ABVD in
      overall survival. INTERPRETATION: Six cycles of BEACOPPescalated significantly
      improves overall survival compared with ABVD and other regimens, and thus we
      recommend this treatment strategy as standard of care for patients with access to
      the appropriate supportive care.

PMID- 23948349
TI  - Long-term results of dose-dense paclitaxel and carboplatin versus conventional
      paclitaxel and carboplatin for treatment of advanced epithelial ovarian,
      fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised,
      controlled, open-label trial.
AB  - BACKGROUND: The primary analysis of the JGOG 3016 trial showed that a dose-dense
      paclitaxel and carboplatin regimen significantly improves progression-free and
      overall survival compared with the conventional regimen as first-line
      chemotherapy for patients with epithelial ovarian, fallopian tube, or primary
      peritoneal cancer. We report the long-term follow-up results for survival.
      METHODS: This randomised controlled trial was done at 85 centres in Japan.
      Patients with stage II-IV ovarian cancer were randomly assigned to receive
      conventional treatment (carboplatin area under the curve [AUC] 6 mg/mL per min
      and paclitaxel 180 mg/m(2) on day 1) or dose-dense treatment (carboplatin AUC 6
      mg/mL per min on day 1 and paclitaxel 80 mg/m(2) on days 1, 8, and 15). The
      treatments were repeated every 3 weeks for six cycles; responding patients had
      three additional cycles. The randomisation was done centrally by telephone or
      fax, stratified by residual disease, stage, and histological type. The primary
      endpoint was progression-free survival; overall survival was a secondary
      endpoint. Long-term information on adverse events was not collected. Efficacy
      analyses were by intention to treat. This study is registered with
      ClinicalTrials.gov, number NCT00226915. FINDINGS: 637 patients were enrolled, of
      whom 631 were analysed (312 assigned to the dose-dense regimen, 319 to the
      conventional regimen). Median follow-up was 76.8 months (IQR 68.9-85.6). Median
      progression-free survival was significantly longer in the dose-dense treatment
      group than in the conventional treatment group (28.2 months [95% CI 22.3-33.8] vs
      17.5 months [15.7-21.7]; hazard ratio [HR] 0.76, 95% CI 0.62-0.91; p=0.0037).
      Median overall survival was 100.5 months (95% CI 65.2-infinity) in the dose-dense
      treatment group and 62.2 months (52.1-82.6) in the conventional treatment group
      (HR 0.79, 95% CI 0.63-0.99; p=0.039). INTERPRETATION: Dose-dense treatment offers
      better survival than conventional treatment and is a potential new standard of
      care for first-line chemotherapy for patients with advanced epithelial ovarian
      cancer.

PMID- 23948350
TI  - Icotinib: kick-starting the Chinese anticancer drug industry.

PMID- 23948352
TI  - Antioxidant and genoprotective effects of spent coffee extracts in human cells.
AB  - Spent coffee has been shown as a good source of hydrophilic antioxidant
      compounds. The ability of two spent coffee extracts rich in caffeoylquinic acids,
      mainly dicaffeoylquinic acids, and caffeine (Arabica filter and Robusta espresso)
      to protect against oxidation and DNA damage in human cells (HeLa) was evaluated
      at short (2 h) and long (24 h) exposure times. Cell viability (MTT) was not
      affected by spent coffee extracts (>80%) up to 1000 MUg/mL after 2 h. Both spent
      coffee extracts significantly reduced the increase of ROS level and DNA strand
      breaks (29-73% protection by comet assay) induced by H2O2. Pretreatment of cells
      with robusta spent coffee extract also decreased Ro photosensitizer-induced
      oxidative DNA damage after 24 h exposure. The higher effectiveness of Robusta
      spent coffee extract, with less caffeoylquinic acids and melanoidins, might be
      due to other antioxidant compounds, such as caffeine and other Maillard reaction
      products. This work evidences the potential antioxidant and genoprotective
      properties of spent coffee in human cells.

PMID- 23948353
TI  - Evaluation of the cytotoxicity, genotoxicity and apoptotic induction of an
      aqueous extract of Achyrocline satureioides (Lam.) DC.
AB  - Achyrocline satureioides is widely consumed as infusion or aperitif and shows
      important therapeutic properties. Previously, we reported absence of genotoxicity
      of cold aqueous extract (CAE) of A. satureioides by Allium test. However, one
      test cannot predict the genotoxic effects of a substance. Thus, the aim of this
      work was to investigate cytotoxicity, genotoxicity and apoptotic ability of CAE
      of A. satureioides. In addition, CAE was chemically characterized. The
      cytotoxicity was evaluated by Trypan blue and MTT assays. The apoptotic capacity
      was evaluated by Hoechst staining and DNA fragmentation-analysis. The
      genotoxicity was studied by comet assay (CA) and micronucleus test. The
      identification and quantification of flavonoids were performed by HPLC-ESI-MS/MS.
      The cytotoxicity studies indicated low toxicity of CAE. In addition, CAE did not
      induce apoptotic effects on human PBMCs. CAE did not show genotoxicity in vitro
      against Vero cells, at 10-50 MUg/mL. CAE did not induce in vivo genotoxic
      effects, but it showed at high concentrations cytotoxicity by micronucleus assay.
      CAE presented flavonoids such as quercetin, 3-O-methylquercetin and luteolin. In
      conclusion, A. satureioides at popularly concentrations used, in aperitif or
      infusion, can be consumed safely because did not show any cytotoxic or genotoxic
      effects.

PMID- 23948351
TI  - Icotinib versus gefitinib in previously treated advanced non-small-cell lung
      cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial.
AB  - BACKGROUND: Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown
      antitumour activity and favourable toxicity in early-phase clinical trials. We
      aimed to investigate whether icotinib is non-inferior to gefitinib in patients
      with non-small-cell lung cancer. METHODS: In this randomised, double-blind, phase
      3 non-inferiority trial we enrolled patients with advanced non-small-cell lung
      cancer from 27 sites in China. Eligible patients were those aged 18-75 years who
      had not responded to one or more platinum-based chemotherapy regimen. Patients
      were randomly assigned (1:1), using minimisation methods, to receive icotinib
      (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease
      progression or unacceptable toxicity. The primary endpoint was progression-free
      survival, analysed in the full analysis set. We analysed EGFR status if tissue
      samples were available. All investigators, clinicians, and participants were
      masked to patient distribution. The non-inferiority margin was 1.14; non
      inferiority would be established if the upper limit of the 95% CI for the hazard
      ratio (HR) of gefitinib versus icotinib was less than this margin. This study is
      registered with ClinicalTrials.gov, number NCT01040780, and the Chinese Clinical
      Trial Registry, number ChiCTR-TRC-09000506. FINDINGS: 400 eligible patients were
      enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by
      mistake and removed from the study, 200 were assigned to icotinib and 199 to
      gefitinib. 395 patients were included in the full analysis set (icotinib, n=199;
      gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression
      free survival (HR 0.84, 95% CI 0.67-1.05; median progression-free survival 4.6
      months [95% CI 3.5-6.3] vs 3.4 months [2.3-3.8]; p=0.13). The most common adverse
      events were rash (81 [41%] of 200 patients in the icotinib group vs 98 [49%] of
      199 patients in the gefitinib group) and diarrhoea (43 [22%] vs 58 [29%]).
      Patients given icotinib had less drug-related adverse events than did those given
      gefitinib (121 [61%] vs 140 [70%]; p=0.046), especially drug-related diarrhoea
      (37 [19%] vs 55 [28%]; p=0.033). INTERPRETATION: Icotinib could be a new
      treatment option for pretreated patients with advanced non-small-cell lung
      cancer.

PMID- 23948354
TI  - Individual and combined developmental toxicity assessment of bisphenol A and
      genistein using the embryonic stem cell test in vitro.
AB  - The potential developmental toxicity of environmental estrogenic endocrine
      disruptors have become a great concern in recent years. In this study, two
      typical environmental oestrogen, namely, bisphenol A (BPA) and genistein (GEN)
      were investigated for potential embryotoxicity using the embryonic stem cell test
      model. Afterwards, a 4*4 full factorial design and the estimated marginal means
      plot were performed to assess the combined effects of these two compounds.
      According to the linear discriminant functions and classification criteria,
      bisphenol A and genistein were classified as weakly embryotoxic and strongly
      embryotoxic respectively. As for combined effects, the overall interaction
      between BPA and GEN on embryonic stem cells (ESCs) differentiation was
      synergistic at low dosages, however, on ESCs and 3T3 cell proliferation, the
      predominate action was additive. Considering the actual daily intake of these
      chemicals, it is concluded that BPA alone might not have adverse reproductive or
      developmental effects on human being. However, given that BPA and GEN do have
      synergistic effect at low concentration, they may disturb normal embryo
      development together, which could result in birth defect and behavioral
      alterations later in life. 

PMID- 23948356
TI  - Potential anti-tumor effects of Mugil cephalus processed roe extracts on colon
      cancer cells.
AB  - The salted-semidried mullet ovary product, bottarga, is a Mediterranean food rich
      in n-3 PUFA EPA and DHA. We studied and compared the effects on cell viability,
      sensitivity to the anti-tumor drug 5-fluorouracil, and lipid composition, in
      colon cancer Caco-2 cells after 24 h incubation with oils and hydrophilic
      extracts obtained from two bottarga samples stored at different conditions. The
      cellular absorption of bottarga lipids was assessed in cancer cells by the
      evaluation of lipid accumulation in cytoplasmic lipid droplets by fluorescence
      microscopy. Bottarga oil showed a significant in vitro inhibitory effect on the
      growth of cancer Caco-2 cells and the ability to potentiate, at non-toxic
      concentration, the growth inhibitory effect of 5-fluorouracil. Moreover, bottarga
      oil induced in cancer Caco-2 cells marked changes in fatty acid composition, with
      a significant accumulation of the n-3 PUFA EPA and DHA, and cytoplasmic lipid
      droplet formation. Also bottarga hydrophilic extract, characterized by means of
      1H NMR spectroscopy, exhibited a reduction in cancer cell viability, without
      affecting cell lipid profile. Cell cholesterol levels were unmodified by all
      treatments. The results showed interesting anti-tumor properties of bottarga
      lipids, and qualify this fish product as a food with nutraceutical properties and
      potential benefits in colon cancer prevention.

PMID- 23948355
TI  - Cytotoxicity and inhibition of intercellular interaction in N2a neurospheroids by
      perfluorooctanoic acid and perfluorooctanesulfonic acid.
AB  - Effects of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS)
      on the neuronal lineage marker expression, cell-cell interaction, caspase-3 mRNA
      transcription and reactive oxygen species production by N2a neuronal cells were
      assesses in 3-dimensional (3D) spheroid cultures, and the cytotoxicity were
      thoroughly compared with those of a conventional 2D monolayer-based toxicity
      assay. Increasing concentrations of PFOA or PFOS resulted in an increase in cell
      death. The half maximal inhibitory concentrations measured with spheroids were
      approximately one and a half times greater than the respective values for
      monolayer cells. Necrosis was prevalent in spheroids regardless of the dose,
      whereas the major injury mechanism in monolayers was dependent on compound
      concentration. Both PFOA and PFOS inhibited neuronal, astrocyte and
      oligodendrocyte marker gene expression by monolayers and spheroids grown under
      undifferentiated and all-trans-retinoic acid-induced differentiating conditions.
      In the presence of PFOA or PFOS, expression levels of E-cadherin and connexin-43
      mRNAs were significantly downregulated, and spheroids were dissociated into
      single cell populations, indicating that the compounds affect the synthesis of E
      cadherin and connexin-43 at the transcriptional level. Results from 3D cultures
      may provide an insight into potential inhibitory mode of action on gap junctional
      intercellular communication. 

PMID- 23948357
TI  - Antibody and T cell responses induced in chickens immunized with avian influenza
      virus N1 and NP DNA vaccine with chicken IL-15 and IL-18.
AB  - We had examined the immunogenicity of a series of plasmid DNAs which include
      neuraminidase (NA) and nucleoprotein (NP) genes from avian influenza virus (AIV).
      The interleukin-15 (IL-15) and interleukin-18 (IL-18) as genetic adjuvants were
      used for immunization in combination with the N1 and NP AIV genes. In the first
      trial, 8 groups of chickens were established with 10 specific-pathogen-free (SPF)
      chickens per group while, in the second trial 7 SPF chickens per group were used.
      The overall N1 enzyme-linked immunosorbent assay (ELISA) titer in chickens
      immunized with the pDis/N1+pDis/IL-15 was higher compared to the chickens
      immunized with the pDis/N1 and this suggesting that chicken IL-15 could play a
      role in enhancing the humoral immune response. Besides that, the chickens that
      were immunized at 14-day-old (Trial 2) showed a higher N1 antibody titer compared
      to the chickens that were immunized at 1-day-old (Trial 1). Despite the delayed
      in NP antibody responses, the chickens co-administrated with IL-15 were able to
      induce earlier and higher antibody response compared to the pDis/NP and
      pDis/NP+pDis/IL-18 inoculated groups. The pDis/N1+pDis/IL-15 inoculated chickens
      also induced higher CD8+ T cells increase than the pDis/N1 group in both trials
      (P<0.05). The flow cytometry results from both trials demonstrated that the
      pDis/N1+pDis/IL-18 groups were able to induce CD4+ T cells higher than the
      pDis/N1 group (P<0.05). Meanwhile, pDis/N1+pDis/IL-18 group was able to induce
      CD8+ T cells higher than the pDis/N1 group (P<0.05) in Trial 2 only. In the
      present study, pDis/NP was not significant (P>0.05) in inducing CD4+ and CD8+ T
      cells when co-administered with the pDis/IL-18 in both trials in comparison to
      the pDis/NP. Our data suggest that the pDis/N1+pDis/IL-15 combination has the
      potential to be used as a DNA vaccine against AIV in chickens. 

PMID- 23948358
TI  - Evaluation of bone response to various anorganic bovine bone xenografts: an
      experimental calvaria defect study.
AB  - This in vivo study investigated the in vivo performance of two newly developed
      synthetic bone substitutes and compared them to commercially available xenografts
      (Bio-Oss, Geistlich Pharma AG, Switzerland; OsteoGraf, Dentsply, USA). The
      materials were tested in a rabbit calvaria model, and the bone forming properties
      were observed at 4 and 8 weeks after implantation by means of histomorphometry
      and micro computed tomography (micro-CT). Defects without any graft material were
      used as negative controls. Micro-CT showed that all materials tested presented
      new bone formation that filled the defects at both time points, whereas the
      negative control presented less bone formation, with soft tissue infiltration
      into the defects. Comparable bone fill percentages were observed for
      histomorphometric and micro-CT results. Even though no statistically significant
      difference was found quantitatively between all of the bone graft substitute
      groups, a higher mean decrease in graft material filling the defects, along with
      higher remodelling activity, was evident for the experimental materials compared
      to the commercially available xenografts at 8 weeks. The results indicate that
      the experimental materials possess high degradability, along with osteoconduction
      comparable to commercially available xenografts. 

PMID- 23948359
TI  - Cost-effectiveness of transcatheter aortic valve implantation (TAVI) for aortic
      stenosis in patients who are high risk or contraindicated for surgery: a model
      based economic evaluation.
AB  - BACKGROUND: Calcific aortic stenosis (AS) is a common valvular heart disease.
      Patients with severe symptomatic AS typically survive less than 3 years. In such
      patients, intervention with surgical aortic valve replacement (SAVR) may increase
      survival. However, in some patients SAVR is associated with a high operative risk
      and medical management is considered appropriate. Transcatheter aortic valve
      implantation (TAVI) is a relatively recent technique to avoid the invasiveness of
      open surgery. This procedure has been used for the treatment of patients with
      severe AS who are unsuitable for SAVR (because it is too high risk and/or for
      other reasons such as suffering from porcelain aorta) and is increasingly being
      considered for other patients. OBJECTIVES: To determine the cost-effectiveness of
      TAVI being made available for patients who are high risk or contraindicated for
      SAVR through a review of existing economic evaluations and development of a
      model. DATA SOURCES AND REVIEW METHODS: Bibliographic databases [MEDLINE, EMBASE,
      The Cochrane Library, Health Technology Assessment (HTA), Database of Abstracts
      of Reviews of Effects (DARE) and NHS Economic Evaluation Database (EED), Centre
      for Reviews and Dissemination HTA, DARE and NHS EED], guideline resources,
      current trials registers, websites/grey literature and manufacturers' websites,
      and consultation with clinical experts were used to identify studies for the
      review and information for the model. Databases were searched from 2007 to
      November 2010. A model was built to assess the cost-effectiveness of TAVI
      separately in patients suitable and unsuitable for SAVR, together with overall
      results for the effect of making TAVI available. Substantial deterministic
      sensitivity analysis was carried out together with probabilistic sensitivity
      analysis. RESULTS: No fully published cost-effectiveness studies were found.
      Modelling patients not suitable for SAVR, the base-case results show TAVI as more
      costly but more effective than medical management, with an incremental cost
      effectiveness ratio (ICER) of L12,900 per quality-adjusted life-year (QALY). The
      ICER was below L20,000 per QALY for over 99% of model runs in the probabilistic
      sensitivity analysis. For patients suitable for SAVR, the comparator with TAVI is
      a mixture of SAVR and medical management. TAVI is both more costly and less
      effective than this comparator assuming that most patients would receive SAVR in
      the absence of TAVI. This is robust to a number of assumption changes about the
      effects of treatment, but sensitive to assumptions about the proportion of
      patients receiving SAVR in the comparator. If the use of TAVI is extended to
      include more patients suitable for SAVR, the overall results from the model
      become less favourable for TAVI. LIMITATIONS: The modelling involves
      extrapolation of short-term data and the comparison between TAVI and SAVR is not
      based on randomised data. More trial data on the latter have been published since
      the modelling was undertaken. CONCLUSIONS: The results for TAVI compared with
      medical management in patients unsuitable for surgery are reasonably robust and
      suggest that TAVI is likely to be cost-effective. For patients suitable for SAVR,
      TAVI could be both more costly and less effective than SAVR. The overall results
      suggest that, if a very substantial majority of TAVI patients are those
      unsuitable for SAVR, the cost-effectiveness of a broad policy of introducing TAVI
      may fall below L20,000 per QALY. Future work required includes the incorporation
      of new data made available after completion of this work. FUNDING: The National
      Institute for Health Research Health Technology Assessment programme.

PMID- 23948360
TI  - The effects of surfactants and solution chemistry on the transport of multiwalled
      carbon nanotubes in quartz sand-packed columns.
AB  - The effect of different surfactants on the transport of multiwalled carbon
      nanotubes (MWCNTs) in quartz sand-packed columns was firstly investigated under
      various conditions. The stable plateau values (C(max)) of the breakthrough curves
      (BTCs), critical PVs (the number of pore volumes of infusions needed to reach the
      C(max)), maximum transport distances (L(max)), deposition rate coefficients (kd)
      and retention rates were calculated to compare the transport and retention of
      MWCNTs under various conditions. Stability of the MWCNT suspensions as a function
      of the influencing factors was examined to reveal the underlying mechanism of the
      MWCNT retention. Results showed that MWCNTs suspended by different surfactants
      presented different BTCs; the MWCNT transport increased with increasing sand size
      and MWCNT concentration; high flow velocity was favorable for the MWCNT
      transport, while high Ca(2+) concentration and low pH were unfavorable for the
      transport; hetero-aggregation, straining and site blocking occurred during the
      transport.

PMID- 23948361
TI  - The journal's performance and upcoming new features.

PMID- 23948362
TI  - Narcotic prescribing habits and other methods of pain control by oral and
      maxillofacial surgeons after impacted third molar removal.
AB  - PURPOSE: It has been suggested that a source of narcotics used for nonmedical
      purposes by young adults is the unused opioids prescribed for the management of
      pain after the removal of impacted third molars. The purpose of the present study
      was to determine whether oral and maxillofacial surgeons routinely prescribe
      larger amounts of a narcotic than would generally be needed for adequate
      postoperative pain control. A secondary goal was to determine whether they use
      methods other than analgesic drugs to minimize postoperative pain and thereby
      reduce the amount of narcotic that might be needed. PATIENTS AND METHODS: An 8
      question survey was sent to 100 randomly selected oral and maxillofacial surgeon
      members of the American Association of Oral and Maxillofacial Surgeons in each of
      the 6 association districts. The questions asked were related to whether a
      narcotic was routinely prescribed for patients who have had impacted teeth
      removed, the most common drug used, and the dosage and number of tablets
      prescribed. The participants were also asked whether they had pretreated patients
      with a nonsteroidal anti-inflammatory drug or had prescribed one along with the
      narcotic, had injected a steroid, or had used a long-lasting local anesthetic
      postoperatively. RESULTS: Only 2 of the 384 respondents stated that they did not
      prescribe a narcotic for patients who had had impacted teeth removed. Hydrocodone
      (5 mg) was the most frequently prescribed narcotic. The number of tablets varied
      from 10 to 40, but the most common number was 20 tablets. However, 80 respondents
      (22%) prescribed more, with 40 prescribing 30 tablets. Also, 80% of the
      respondents injected their patients with a steroid, and 62% injected a long
      lasting local anesthetic postoperatively. Only 34% pretreated their patients with
      a nonsteroidal anti-inflammatory drug, but 66% recommended such use
      postoperatively. CONCLUSIONS: Most oral and maxillofacial surgeons prescribe
      analgesic drugs of an appropriate type and dosage and use proper adjunctive pain
      control measures to supplement these drugs. However, our findings also indicated
      that more than 20% prescribe more tablets than would generally be necessary to
      control the postoperative pain after the removal of impacted third molars. This
      could be a source of drug diversion and nonmedical use by young adults and should
      be avoided.

PMID- 23948363
TI  - Correlation among the changes observed in temporomandibular joint internal
      derangements assessed by magnetic resonance in symptomatic patients.
AB  - PURPOSE: The objective was to assess possible correlations among the anatomy and
      position of the articular disc, the morphology of the articular eminence and of
      the condyle, and the presence of joint effusion. MATERIALS AND METHODS: Magnetic
      resonance images of 142 joints of symptomatic patients were assessed. The
      articular disc was classified as normal, elongated, or folded; displacement was
      classified as normal, anterior with reduction, anterior without reduction, or
      posterior, lateral, or medial; the condyle was classified as rounded, convex,
      flattened, or angulated; and the articular eminence was classified as box,
      sigmoid, flattened, or deformed. RESULTS: The most frequent forms of the
      articular disc, articular eminence, and condyle were normal, box, and flattened,
      respectively. Associations were confirmed between the form of the articular disc
      and its anterior and lateral positions; between the form of the condyle and an
      anterior position of the disc; and between the form of the articular eminence and
      the form of the disc. The form of the articular eminence was the only variant
      that was not associated to the presence of joint effusion. CONCLUSIONS: Magnetic
      resonance imaging allowed the clear observation of articular structures, without
      attributing a cause-and-effect relation. The prevalence of changes observed was
      associated with the diagnosis of internal derangement and was statistically
      proved.

PMID- 23948364
TI  - Horizontal posterior ridge augmentation: the use of a collagen membrane over a
      bovine particulate graft: technique note.
AB  - The purpose of this technique note is to describe an improvement of a previously
      published method to augment the thin posterior mandibular ridge. The technique
      uses a subperiosteal tunnel to place a collagen membrane within the tunnel to
      maintain the shape of the augmentation. After the collagen membrane has been
      placed, a sintered xenograft is packed as an onlay graft, with implant placement
      6 to 9 months later. 

PMID- 23948365
TI  - Evolution of the bacterial organelle responsible for magnetotaxis.
AB  - There are few examples of protein- and lipid-bounded organelles in bacteria that
      are encoded by conserved gene clusters and lead to a specific function. The
      magnetosome chain represents one of these rare examples and is responsible for
      magnetotaxis in magnetotactic bacteria (MTB), a behavior thought to aid in
      finding their optimal growth conditions. The origin and evolution of the
      magnetotaxis is still a matter of debate. Recent breakthroughs in isolation,
      cultivation, single-cell separation, and whole-genome sequencing have generated
      abundant data that give new insights into the biodiversity and evolution of MTB. 

PMID- 23948366
TI  - Optimisation of an MDCT abdominal protocol: Image quality assessment of standard
      vs. iterative reconstructions.
AB  - This work aims to construct a method to objectively evaluate CT image quality
      when new clinical protocol performances must be compared with a standard
      reference. We compare iterative reconstruction in the image space with filtered
      back projection reconstruction and accurately quantify the dose reduction. The
      comparison strategy accounts for both physical and clinical image qualities that
      are evaluated using a standard metric. The quasi-ideal observer metric is also
      explored to verify its reportedly high correlation with perceived image quality.
      Water or spatial resolution phantom images are used to characterise the physical
      image quality using the classic metrics in the Fourier domain by calculating the
      modulation transfer functions and noise power spectra (NPS). The clinical-image
      quality is evaluated with a 4-alternative forced-choice test. The human observers
      are asked to detect a positive image that contains a simulated lesion in a
      background image. Then, the same positive images are characterised with the quasi
      ideal observer metric, which calculates the non-prewhitening matched filter
      signal-to-noise ratio (SNRNPWMF). Iterative reconstruction strongly reduces the
      image noise, but the NPS are slightly shifted to lower frequencies, which gives
      the images a coarse graininess. Compared with the reference FBP protocol for
      abdomen exams, the highest dose reduction is 40% if the standard metric is used
      and 30% if the SNRNPWMF metric is used. The detectability test results achieve a
      better correlation with SNRNPWMF than with the standard metric. The identified
      Fourier metric is a useful descriptor of human quality perception and can be used
      for future protocol optimisation. 

PMID- 23948367
TI  - Is IMAT the ultimate evolution of conformal radiotherapy? Dosimetric comparison
      of helical tomotherapy and volumetric modulated arc therapy for oropharyngeal
      cancer in a planning study.
AB  - BACKGROUND: Intensity Modulated Arc Therapy (IMAT) can be planned and delivered
      via several techniques. Advanced Radiotherapy (ARTORL) is a prospective study
      that aims to evaluate the treatment costs and clinical aspects of implementing
      these IMAT techniques for head and neck cancers. In this context, we evaluated
      the potential dosimetric gain of Helical Tomotherapy (TomoTherapy, Accuray, HT)
      versus VMAT (Rapid'Arc((r)), Varian Medical System, RA) for oropharyngeal cancer
      (OC). MATERIAL AND METHODS: Thirty patients were selected from our database in
      whom bilateral neck irradiation and treatment to the primary were indicated. Each
      patient was planned twice using both HT and RA planning systems using a
      simultaneous integrated boost approach. For the planning target volumes (PTV) and
      organs at risk, ICRU 83 reporting guidelines were followed. RA and HT plans were
      compared using paired Student's t-test. RESULTS: RA and HT produced plans with a
      good coverage of PTVs and acceptable sparing of OARs. Although some dosimetric
      differences were statistically significant, they remained small. However, the
      near maximal dose to the PRV of spinal cord and brain stem was lower with HT.
      Regarding normal tissue, HT increased the volume irradiated at doses between 4
      and 20 Gy compared to RA. CONCLUSION: In OC, HT and RA showed similar dosimetric
      results. They represent the maximum gains obtained with photon beams. The
      medicoeconomic evaluation of our study is ongoing and may reveal differences
      between these techniques in terms of MU number, fraction time, and clinical
      evaluation.

PMID- 23948368
TI  - Exposure to monocrotophos pesticide causes disruption of the hypothalamic
      pituitary-thyroid axis in adult male goldfish (Carassius auratus).
AB  - The thyroid hormones (THs) 3,3',5-triiodo-l-thyronine (T3) and l-thyroxine (T4)
      exert a wide range of biological effects on physiological processes of fish. To
      elucidate the thyroid disruption effects of monocrotophos (MCP), an
      organophosphate pesticide, on male goldfish (Carassius auratus), thyroid follicle
      histology, plasma total T3 (TT3), total T4 (TT4), free T3 (FT3) and free T4
      levels, and the mRNA expression of indices involved in the hypothalamic-pituitary
      thyroid axis (HPT axis) were examined following 21-day exposure to 0.01, 0.10 and
      1.00mg/L of a 40% MCP-based pesticide. The results showed that MCP exposure
      induced the hyperplasia and hypertrophy of thyroid follicular epithelium and led
      to decreased plasma TT3 levels and TT3-to-TT4 ratios, without effect on plasma
      TT4 levels. Profiles of the changes in the relative abundance of deiodinase (D1,
      D2 and D3) transcripts were observed in the liver, brain and kidneys, during MCP
      exposure. An increase in the metabolism of T3, expressed as highly elevated
      hepatic d1 and d3 mRNA levels, might be associated with the reduction in plasma
      TT3 levels in both the 0.01 and 0.10mg/L groups, while in the 1.00mg/L MCP group,
      inhibited hepatic d2 transcripts might have also resulted in decreased TT3 levels
      by preventing the activation of T4 to T3. As a compensatory response to decreased
      T3 levels, pituitary thyroid-stimulating hormone beta subunit mRNA transcription
      was up-regulated by the MCP pesticide. Decreases in plasma FT3 levels were also
      correlated with the modulation of hepatic transthyretin mRNA expression. Overall,
      the MCP pesticide exhibited thyroid-disrupting effects via interference with the
      HPT axis at multiple potential sites, resulting in disturbance of TH homeostasis.

PMID- 23948369
TI  - Influence of temperature on the corticosterone stress-response: an experiment in
      the Children's python (Antaresia childreni).
AB  - To cope with environmental challenges, organisms have to adjust their behaviours
      and their physiology to the environmental conditions they face (i.e. allostasis).
      In vertebrates, such adjustments are often mediated through the secretion of
      glucocorticoids (GCs) that are well-known to activate and/or inhibit specific
      physiological and behavioural traits. In ectothermic species, most processes are
      temperature-dependent and according to previous studies, low external
      temperatures should be associated with low GC concentrations (both baseline and
      stress-induced concentrations). In this study, we experimentally tested this
      hypothesis by investigating the short term influence of temperature on the GC
      stress response in a squamate reptile, the Children's python (Antaresia
      childreni). Snakes were maintained in contrasting conditions (warm and cold
      groups), and their corticosterone (CORT) stress response was measured (baseline
      and stress-induced CORT concentrations), within 48h of treatment. Contrary to our
      prediction, baseline and stress-induced CORT concentrations were higher in the
      cold versus the warm treatment. In addition, we found a strong negative
      relationship between CORT concentrations (baseline and stress-induced) and
      temperature within the cold treatment. Although it remains unclear how cold
      temperatures can mechanistically result in increased CORT concentrations, we
      suggest that, at suboptimal temperature, high CORT concentrations may help the
      organism to maintain an alert state. 

PMID- 23948370
TI  - Chronically raised glucocorticoids reduce innate immune function in Belding's
      ground squirrels (Urocitellus beldingi) after an immune challenge.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis releases glucocorticoids (GCs), or
      stress hormones, during the vertebrate stress response. GCs can both enhance and
      suppress the immune system depending on whether the experienced stressor is acute
      or chronic and what aspect of immune function is measured. More research is
      needed to fully understand how the immune system reacts to stressors. In this
      study, we examined the effects of chronically raised GCs on innate immune
      function in Belding's ground squirrels (Urocitellus beldingi). We measured immune
      function with a bacteria killing ability (BKA) assay, an integrative and
      functional assessment of an animal's ability to clear a bacterial infection. All
      studies to date have examined how acute stressors or repeated social stressors
      impact BKA. This study is the first to our knowledge to investigate how
      chronically raised GCs impact BKA both before and after an immune challenge. We
      noninvasively raised GCs in treatment squirrels for six days and then gave them,
      and a group of untreated (control) squirrels, an injection of lipopolysaccharide
      (LPS) to stimulate their innate immune system. Treatment squirrels exhibited
      lower BKA after, but not before, being challenged with LPS. These results suggest
      that experiencing chronic stress may not be detrimental to immune functioning
      until an individual is challenged with an infection. 

PMID- 23948372
TI  - Lacosamide as an adjunctive therapy in pediatric patients with refractory focal
      epilepsy.
AB  - PURPOSE: To evaluate the efficacy and safety of lacosamide in pediatric patients
      with refractory focal epilepsy. METHODS: We reviewed retrospectively the medical
      records of children younger than 18 years of age treated at Seoul National
      University Bundang Hospital, in whom oral lacosamide was used as an adjunctive
      treatment for refractory focal epilepsy. Clinical information regarding the
      patients' epilepsy and the outcome of lacosamide treatment was gathered and
      analyzed. RESULTS: Twenty-one patients (16 boys, 5 girls) were included, with a
      median age of 13.9 (range, 1.2-17.9) years. The mean number of concomitant
      antiepileptic drugs was 3.0 (range, 1-6) and the mean duration of follow-up was
      10.1 (range, 6.1-13.0) months. The mean maintenance dose of lacosamide was 5.4
      (range, 1.4-9.8) mg/kg/day. Fourteen patients (67%) were responders; four of
      these were seizure free at the last follow-up. Seven patients (33%) were
      nonresponders: two of these presented with <50% seizure reduction and five showed
      no change in seizure frequency. Two patients (10%) discontinued oral lacosamide
      because of adverse events (aggressive behavior and depression). Mild transient
      treatment-related adverse events were observed in eight of the 21 patients (38%).
      CONCLUSIONS: Lacosamide represents a useful drug that is effective for a wide
      range of pediatric refractory focal epilepsy and is well tolerated.

PMID- 23948371
TI  - Tuberal hypothalamic expression of the glial intermediate filaments, glial
      fibrillary acidic protein and vimentin across the turkey hen (Meleagris
      gallopavo) reproductive cycle: Further evidence for a role of glial structural
      plasticity in seasonal reproduction.
AB  - Glia regulate the hypothalamic-pituitary-gonadal (HPG) axis in birds and mammals.
      This is accomplished mechanically by ensheathing gonadotrophin-releasing hormone
      I (GnRH) nerve terminals thereby blocking access to the pituitary blood supply,
      or chemically in a paracrine manner. Such regulation requires appropriate spatial
      associations between glia and nerve terminals. Female turkeys (Meleagris
      gallopavo) use day length as a primary breeding cue. Long days activate the HPG
      axis until the hen enters a photorefractory state when previously stimulatory day
      lengths no longer support HPG-axis activity. Hens must then be exposed to short
      days before reactivation of the reproductive axis occurs. As adult hens have
      discrete inactive reproductive states in addition to a fertile state, they are
      useful for examining the glial contribution to reproductive function. We
      immunostained tuberal hypothalami from short and long-day photosensitive hens,
      plus long-day photorefractory hens to examine expression of two intermediate
      filaments that affect glial morphology: glial fibrillary acidic protein (GFAP)
      and vimentin. GFAP expression was drastically reduced in the central median
      eminence of long day photosensitive hens, especially within the internal zone.
      Vimentin expression was similar among groups. However, vimentin-immunoreactive
      fibers abutting the portal vasculature were significantly negatively correlated
      with GFAP expression in the median eminence, which is consistent with our
      hypothesis for a reciprocal relationship between GFAP and vimentin expression. It
      appears that up-regulation of GFAP expression in the central median eminence of
      turkey hens is associated with periods of reproductive quiescence and that
      photofractoriness is associated with the lack of a glial cytoskeletal response to
      long days. 

PMID- 23948373
TI  - Study of insulin resistance in cybrid cells harboring diabetes-susceptible and
      diabetes-protective mitochondrial haplogroups.
AB  - AIM: This study aims to elucidate the independent role of mitochondria in the
      pathogenesis of insulin resistance (IR). METHODS: Cybrids derived from 143B
      osteosarcoma cell line and harboring the same nuclear DNA but different
      mitochondrial haplogroups were studied. Cybrid B4 (the major diabetes-susceptible
      haplogroup in Chinese population), cybrid D4 (the major diabetes-resistant
      haplogroup in Chinese population) and cybrid N9 (the diabetes-resistant
      haplogroup in Japanese population) were cultured in a medium containing 25 mM
      glucose and stimulated with 0 MUM, 0.1 MUM, and 1.0 MUM insulin. We compared the
      insulin activation of PI3K-Akt (glucose uptake) and ERK-MAPK (pro-inflammation)
      signaling pathways, intracellular and mitochondrial oxidative stress (DCF and
      MitoSOX Red), and their responses to the antioxidant N-acetylcysteine (NAC).
      RESULTS: Upon insulin treatment, the translocation of cytoplasmic GLUT1/GLUT4 to
      the cell membrane in cybrid D4 and N9 cells increased significantly, whereas the
      changes in B4 cells were not or less significant. On the contrary, the ratio of
      insulin-induced JNK and P38 to Akt phosphorylation was significantly greater in
      cybrid B4 cells than in cybrid D4 and N9 cells. The levels of DCF and MitoSOX
      Red, which are indicative of the oxidative stress, were significantly higher in
      the B4 cells in basal conditions and after insulin treatment. Following treatment
      with the antioxidant NAC, cybrid B4 cells showed significantly reduced insulin
      induced phosphorylation of P38 and increased GLUT1/GLUT4 translocation to the
      cell membrane, suggesting that NAC may divert insulin signaling from pro
      inflammation to glucose uptake. CONCLUSIONS: Mitochondria play an independent
      role in the pathogenesis of IR, possibly through altered production of
      intracellular ROS.

PMID- 23948374
TI  - Vector field statistical analysis of kinematic and force trajectories.
AB  - When investigating the dynamics of three-dimensional multi-body biomechanical
      systems it is often difficult to derive spatiotemporally directed predictions
      regarding experimentally induced effects. A paradigm of 'non-directed' hypothesis
      testing has emerged in the literature as a result. Non-directed analyses
      typically consist of ad hoc scalar extraction, an approach which substantially
      simplifies the original, highly multivariate datasets (many time points, many
      vector components). This paper describes a commensurately multivariate method as
      an alternative to scalar extraction. The method, called 'statistical parametric
      mapping' (SPM), uses random field theory to objectively identify field regions
      which co-vary significantly with the experimental design. We compared SPM to
      scalar extraction by re-analyzing three publicly available datasets: 3D knee
      kinematics, a ten-muscle force system, and 3D ground reaction forces. Scalar
      extraction was found to bias the analyses of all three datasets by failing to
      consider sufficient portions of the dataset, and/or by failing to consider
      covariance amongst vector components. SPM overcame both problems by conducting
      hypothesis testing at the (massively multivariate) vector trajectory level, with
      random field corrections simultaneously accounting for temporal correlation and
      vector covariance. While SPM has been widely demonstrated to be effective for
      analyzing 3D scalar fields, the current results are the first to demonstrate its
      effectiveness for 1D vector field analysis. It was concluded that SPM offers a
      generalized, statistically comprehensive solution to scalar extraction's over
      simplification of vector trajectories, thereby making it useful for objectively
      guiding analyses of complex biomechanical systems. 

PMID- 23948375
TI  - In-vivo mitral annuloplasty ring transducer: implications for implantation and
      annular downsizing.
AB  - Mitral annuloplasty has been a keystone to the success of mitral valve repair in
      functional mitral regurgitation. Understanding the complex interplay between
      annular-ring stresses and left ventricular function has significant implications
      for patient-ring selection, repair failure, and patient safety. A step towards
      assessing these challenges is developing a transducer that can be implanted in
      the exact method as commercially available rings and can quantify
      multidirectional ring loading. An annuloplasty ring transducer was developed to
      measure stresses at eight locations on both the in-plane and out-of-plane
      surfaces of an annuloplasty ring's titanium core. The transducer was implanted in
      an ovine subject using 10 sutures at near symmetric locations. At implantation,
      the ring was observed to undersize the mitral annulus. The flaccid annulus
      exerted both compressive (-) and tensile stresses (+) on the ring ranging from 
      3.17 to 5.34 MPa. At baseline hemodynamics, stresses cyclically changed and
      peaked near mid-systole. Mean changes in cyclic stress from ventricular diastole
      to mid-systole ranged from -0.61 to 0.46 MPa (in-plane direction) and from -0.49
      to 1.13 MPa (out-of-plane direction). Results demonstrate the variability in ring
      stresses that can be introduced during implantation and the cyclic contraction of
      the mitral annulus. Ring stresses at implantation were approximately 4 magnitudes
      larger than the cyclic changes in stress throughout the cardiac cycle. These
      methods will be extended to ring transducers of differing size and geometry. Upon
      additional investigation, these data will contribute to improved knowledge of
      annulus-ring stresses, LV function, and the safer development of mitral repair
      techniques.

PMID- 23948376
TI  - Cellular prion proteins in humans and cattle but not sheep are characterized by a
      low-solubility phenotype.
AB  - A feature of transmissible spongiform encephalopathies is the accumulation of
      infectious prion proteins (PrP(Sc)), which are formed by the conversion of
      physiological prion proteins (PrP(C)). As PrP(C), which is modified
      posttranslationally with various types of glycoproteins, serves as the substrates
      for PrP(Sc) conversion, various PrP(C) subtypes may play a role in the formation
      of PrP(Sc) and species-specific transmission; the cattle disease BSE is
      transmissible naturally to humans, but the sheep disease scrapie is not. To
      reveal new mechanisms modulating prion conversion, we analyzed the PrP(C)
      profiles by determining the differential PrP(C) protein solubilities in the
      anionic and nonionic detergents N-lauroylsarcosine, N-octyl-beta-D
      glucopyranoside, CHAPS and deoxycholic acid. We compared the resulting solubility
      profiles of human PrP(C) with the solubility profiles of PrP(C) from sheep and
      cattle. The PrP(C) subtypes were differentially soluble. However, non
      glycosylated PrP(C) from cattle and human was found explicitly in the insoluble
      fraction, while non-glycosylated ovine PrP(C) was detected in the soluble
      fraction. These findings indicate the existence of low-solubility PrP(C)
      phenotypes in cattle and humans.

PMID- 23948377
TI  - The uncertainties of certainty: using LV function to predict arrhythmic event
      after AMI.

PMID- 23948378
TI  - U-shaped mechanical activation 4 U?

PMID- 23948379
TI  - The red devil revisited.

PMID- 23948380
TI  - Reply: Bicuspid aortic valve phenotype and aortopathy: nomenclature and role of
      aortic hemodynamics.

PMID- 23948381
TI  - Bicuspid aortic valve phenotype and aortopathy: nomenclature and role of aortic
      hemodynamics.

PMID- 23948382
TI  - MDCT in TAVR for better implant angle and outcomes.

PMID- 23948383
TI  - Reply: MDCT in TAVR for better implant angle and outcomes.

PMID- 23948384
TI  - Cardiac resynchronization: the flow of activation sequence.

PMID- 23948385
TI  - Payment changes in CV imaging.

PMID- 23948386
TI  - Comorbidity: a multidimensional approach.
AB  - Comorbidity represents an extremely complex domain of research. An individual
      entity, the patient, is the center of gravity of a system characterized by
      multiple, complex, and interrelated conditions, disorders, or diseases. Such
      complexity is influenced by uncertainty that is difficult to decipher and is
      proportional to the number of associated morbidities. Computational scientists
      usually provide meta-analysis studies aimed at integrating various types of
      evidence, but in our opinion they may help reformulate comorbidity by
      emphasizing, in particular, two aspects: (i) a systems approach, which allows for
      an ensemble view of comorbidity, and offers a model representation generalizable
      to multimorbidity; and (ii) a dynamic network inference approach, which is
      indicated for the analysis of links among morbidities and evaluation of risk.
      Notably, the main question remains whether such instruments suggest a shift of
      paradigm providing prospective impact on medical practice. We have identified in
      the simultaneous consideration of multiple dimensions linked to comorbidity
      complexity the rationale for such translation. 

PMID- 23948387
TI  - Illusion of control: the role of personal involvement.
AB  - The illusion of control consists of overestimating the influence that our
      behavior exerts over uncontrollable outcomes. Available evidence suggests that an
      important factor in development of this illusion is the personal involvement of
      participants who are trying to obtain the outcome. The dominant view assumes that
      this is due to social motivations and self-esteem protection. We propose that
      this may be due to a bias in contingency detection which occurs when the
      probability of the action (i.e., of the potential cause) is high. Indeed,
      personal involvement might have been often confounded with the probability of
      acting, as participants who are more involved tend to act more frequently than
      those for whom the outcome is irrelevant and therefore become mere observers. We
      tested these two variables separately. In two experiments, the outcome was always
      uncontrollable and we used a yoked design in which the participants of one
      condition were actively involved in obtaining it and the participants in the
      other condition observed the adventitious cause-effect pairs. The results support
      the latter approach: Those acting more often to obtain the outcome developed
      stronger illusions, and so did their yoked counterparts. 

PMID- 23948388
TI  - Does viotin activate violin more than viocin? On the use of visual cues during
      visual-word recognition.
AB  - The vast majority of neural and computational models of visual-word recognition
      assume that lexical access is achieved via the activation of abstract letter
      identities. Thus, a word's overall shape should play no role in this process. In
      the present lexical decision experiment, we compared word-like pseudowords like
      viotin (same shape as its base word: violin) vs. viocin (different shape) in
      mature (college-aged skilled readers), immature (normally reading children), and
      immature/impaired (young readers with developmental dyslexia) word-recognition
      systems. Results revealed similar response times (and error rates) to consistent
      shape and inconsistent-shape pseudowords for both adult skilled readers and
      normally reading children - this is consistent with current models of visual-word
      recognition. In contrast, young readers with developmental dyslexia made
      significantly more errors to viotin-like pseudowords than to viocin-like
      pseudowords. Thus, unlike normally reading children, young readers with
      developmental dyslexia are sensitive to a word's visual cues, presumably because
      of poor letter representations. 

PMID- 23948389
TI  - An experimental validation method for questioning techniques that assess
      sensitive issues.
AB  - Studies addressing sensitive issues often yield distorted prevalence estimates
      due to socially desirable responding. Several techniques have been proposed to
      reduce this bias, including indirect questioning, psychophysiological lie
      detection, and bogus pipeline procedures. However, the increase in resources
      required by these techniques is warranted only if there is a substantial increase
      in validity as compared to direct questions. Convincing demonstration of superior
      validity necessitates the availability of a criterion reflecting the "true"
      prevalence of a sensitive attribute. Unfortunately, such criteria are notoriously
      difficult to obtain, which is why validation studies often proceed indirectly by
      simply comparing estimates obtained with different methods. Comparative
      validation studies, however, provide weak evidence only since the exact increase
      in validity (if any) remains unknown. To remedy this problem, we propose a simple
      method that allows for measuring the "true" prevalence of a sensitive behavior
      experimentally. The basic idea is to elicit normatively problematic behavior in a
      way that ensures conclusive knowledge of the prevalence rate of this behavior.
      This prevalence measure can then serve as an external validation criterion in a
      second step. An empirical demonstration of this method is provided. 

PMID- 23948390
TI  - Locus of backward crosstalk effects on task 1 in a psychological refractory
      period task.
AB  - Our performance on a task decreases when the task is in a dual-task situation
      than when it is in isolation. An important experimental setting for dual-task
      situation is the psychological refractory period (PRP) paradigm, and the dual
      task performance decrements in the PRP paradigm are referred to as PRP
      interference. The standard response-selection bottleneck (RSB) models state that
      the response-selection stage of the second task (T2) cannot start until the
      response-selection stage of the first task (T1) finishes, resulting in the PRP
      interference. Contrary to the prediction of RSB models, several researchers have
      found T2's modulations on T1's performance, and have suggested that T1's
      selection-related processes are affected by T2's selection-related processes,
      referred to as backward crosstalk effects. The locus of backward crosstalk
      effects is not clear, however, because RTs were measured in most previous
      studies. By using semantically unrelated stimuli and responses and by measuring
      T1's lateralized readiness potential, we examined the locus of backward crosstalk
      effects. We found that the interval between T1's stimulus onset and the stimulus
      locked LRP onset was affected, suggesting T2's response selection starts before
      T1's selection is complete. The present result provided electrophysiological
      evidence focusing on T1's changes in favor of the hypothesis of parallel response
      selection in the PRP paradigm. 

PMID- 23948391
TI  - Overnight storage of removable dentures in alkaline peroxide-based tablets
      affects biofilm mass and composition.
AB  - BACKGROUND: Clinical guidelines for denture care are available, but evidence for
      optimal nocturnal storage is scarce. The aim of the study was to compare the role
      of the overnight storage state on plaque growth and composition on acrylic
      removable dentures. METHODS: In a parallel-group randomized controlled trial of
      51 institutionalized participants, 3 denture overnight preservation methods were
      considered: (i) in water, (ii) dry or (iii) in water with added alkaline peroxide
      based cleansing tablet. Biofilm samples were taken on day 7 (developing biofilm -
      dBF) and day 14 (maturing biofilm - mBF) from a mechanically uncleaned,
      standardized region, situated distally to the second lower premolars. Total and
      individual levels of selected perio-pathogenic and commensal species (n=20), and
      of Candida albicans were calculated by PCR. Differences between storage
      conditions (water/dry/tablet) and between the samples (dBF/mBF) were assessed by
      means of unpaired and paired t-tests respectively, with alpha=5%. RESULTS:
      Overnight denture storage with cleansing tablet significantly decreased the total
      bacterial level of dBF and mBF up to 13.8%. Fn, Ec, Cs, Sc, Ao and Vp counts were
      particularly affected by tablet care. Significant lower amounts of Candida
      albicans for tablet storage compared to water preservation were recorded in dBF
      and mBF (-69.3 +/- 3.8% and -75.9 +/- 3.2% respectively). The mass and
      pathogenicity of dBF and mBF was equal, irrespective of the overnight storage
      intervention. CONCLUSIONS: The use of cleansing tablets for acrylic removable
      denture overnight storage reduces denture biofilm mass and pathogenicity compared
      to dry and water preservation, and may contribute to the overall systemic health.
      CLINICAL SIGNIFICANCE: Evidence-based clinical guidelines for overnight storage
      of removable acrylic dentures are lacking. The findings of this study indicate
      that alkaline peroxide-based cleansing tablets decrease bacterial and Candida
      levels in denture biofilms in case of poor oral hygiene. This provides evidence
      for a clinical guideline to minimize microbial load of dentures, thereby reducing
      associated systemic health risks.

PMID- 23948392
TI  - Relationship between daily habits, Streptococcus mutans, and caries among
      schoolboys.
AB  - OBJECTIVES: The purpose of this study was to examine the associations between
      daily habits, Streptococcus mutans, and caries using International Caries
      Detection and Assessment System Caries Index (ICDAS CI); and compare it to the
      DMF index. SUBJECTS AND METHODS: Altogether 122 children were examined and
      interviewed. Saliva and plaque samples were collected and analyzed by Dentocult
      SM((r)) Strip Mutans test. ICDAS CI was calculated by counting all ICDAS caries
      scores of all surfaces divided by total number of carious teeth. RESULTS: ICDAS
      CI was significantly (p<0.01) and strongly associated with DMFT/dmft (rho=0.72),
      DMFS/dmfs (rho=0.72), total number of carious teeth (DT/dt) (rho=0.77), enamel
      caries surfaces (rho=0.61) and dentine caries surfaces (rho=0.75). Plaque S.
      mutans was significantly (p<0.05) correlated with ICDAS CI and DT/dt. Children
      who brushed once a day or more had significantly lower ICDAS CI (p<0.01).
      Children who consumed sweets or drank soft drinks more than once a day had
      significantly higher ICDAS CI (p<0.05). No significant association was found
      between ICDAS CI and frequency of flossing, use of mouthrinse, or gum chewing.
      CONCLUSION: ICDAS CI seems to have similar trends as DMF indices, but includes
      more information about the stage, severity, and progress of the caries lesions of
      the patient.

PMID- 23948393
TI  - Effect of 3D microgroove surface topography on plasma and cellular fibronectin of
      human gingival fibroblasts.
AB  - OBJECTIVES: Fibronectin (FN), an extracellular matrix (ECM) glycoprotein, is a
      key factor in the compatibility of dental implant materials. Our objective was to
      determine the optimal dimensions of microgrooves in the transmucosal part of a
      dental implant, for optimal absorption of plasma FN and expression of cellular FN
      by human gingival fibroblasts (HGFs). METHODS: Microgroove titanium surfaces were
      fabricated by photolithography with parallel grooves: 15MUm, 30MUm, or 60MUm in
      width and 5MUm or 10MUm in depth. Smooth titanium surfaces were used as controls.
      Surface hydrophilicity, plasma FN adsorption and cellular FN expression by HGFs
      were measured for both microgroove and control samples. RESULTS: We found that
      narrower and deeper microgrooves amplified surface hydrophobicity. A 15-MUm wide
      microgroove was the most hydrophobic surface and a 60-MUm wide microgroove was
      the most hydrophilic. The latter had more expression of cellular FN than any
      other surface, but less absorption of plasma FN than 15-MUm wide microgrooves.
      Variation in microgroove depth did not appear to effect FN absorption or
      expression unless the groove was narrow (~15 or 30MUm). In those instances, the
      shallower depths resulted in greater expression of cellular FN. CONCLUSIONS: Our
      microgrooves improved expression of cellular FN, which functionally compensated
      for plasma FN. A microgroove width of 60MUm and depth of 5 or 10MUm appears to be
      optimal for the transmucosal part of the dental implant.

PMID- 23948395
TI  - Do ultrasonic dental scalers interfere with implantable cardioverter
      defibrillators? An in vivo investigation.
AB  - OBJECTIVES: To test the in vivo effects of an ultrasonic dental scaler on various
      implanted cardioverter defibrillator (ICD) models. METHODS: 12 consecutive
      patients with ICDs had continuous both electrocardiogram monitoring and device
      interrogation to detect interferences during the use of an ultrasonic dental
      scaler. RESULTS: No interferences were detected by any ICD. Evaluation of the
      electrocardiograms for each patient failed to show any abnormalities in pacing
      during testing. CONCLUSION: The results of this study suggest that the routinary
      clinic use of piezoelectric dental scalers do not interfere with the functioning
      of any of the tested ICDs. CLINICAL SIGNIFICANCE: Ultrasonic dental scalers have
      been suspected of electromagnetic interference (EMI) with the normal functioning
      of ICDs and the use of this type of equipment for patients with these devices has
      been controversial. This is the first in vivo study to investigate EMI of ICD
      activity during the operation with ultrasonic dental scaler.

PMID- 23948394
TI  - Dental plaque microcosm response to bonding agents containing quaternary ammonium
      methacrylates with different chain lengths and charge densities.
AB  - OBJECTIVES: Antibacterial bonding agents are promising to combat bacteria and
      caries at tooth-restoration margins. The objectives of this study were to
      incorporate new quaternary ammonium methacrylates (QAMs) to bonding agent and
      determine the effects of alkyl chain length (CL) and quaternary amine charge
      density on dental plaque microcosm bacteria response for the first time. METHODS:
      Six QAMs were synthesized with CL=3, 6, 9, 12, 16, 18. Each QAM was incorporated
      into Scotchbond multi-purpose (SBMP). To determine the charge density effect,
      dimethylaminododecyl methacrylate (DMAHDM, CL=16) was mixed into SBMP at mass
      fraction=0%, 2.5%, 5%, 7.5%, 10%. Charge density was measured using a fluorescein
      dye method. Dental plaque microcosm using saliva from ten donors was tested.
      Bacteria were inoculated on resins. Early-attachment was tested at 4h. Biofilm
      colony-forming units (CFU) were measured at 2 days. RESULTS: Incorporating QAMs
      into SBMP reduced bacteria early-attachment. Microcosm biofilm CFU for CL=16 was
      4 log lower than SBMP control. Charge density of bonding agent increased with
      DMAHDM content. Bacteria early-attachment decreased with increasing charge
      density. Biofilm CFU at 10% DMAHDM was reduced by 4 log. The killing effect was
      similarly-strong against total microorganisms, total streptococci, and mutans
      streptococci. CONCLUSIONS: Increasing alkyl chain length and charge density of
      bonding agent was shown for the first time to decrease microcosm bacteria
      attachment and reduce biofilm CFU by 4 orders of magnitude. Novel antibacterial
      resins with tailored chain length and charge density are promising for wide
      applications in bonding, cements, sealants and composites to inhibit biofilms and
      caries.

PMID- 23948396
TI  - Hyperthermia-induced seizures: development of hyperthermia-prone and hyperthermia
      resistant rats.
AB  - Febrile seizures (FS), as a multifactorial and genetic disease, are the most
      common type of convulsive event in infants and young children. Their genetic
      basis, however, remains elusive. To investigate the genetic mechanisms involved
      in FS and to identify novel susceptibility genes, we developed two new strains of
      rats that are hyperthermia-prone (HP, lower seizure threshold) and hyperthermia
      resistant (HR, higher seizure threshold) using an established model of
      hyperthermia-induced seizures combined with selective breeding process. With each
      subsequent generation, the morbidity of the FS gradually increased in the HP
      group and gradually decreased in the HR group. Changes in seizure susceptibility
      between the two genotypes were investigated using kainic acid (KA)-induced
      seizures and electroencephalography (EEG). The HP rats had a greater seizure
      severity compared with the HR rats. Our findings may be a significant step toward
      discovering the genetic mechanisms involved in FS and may elucidate the
      pathogenesis of this disorder. 

PMID- 23948397
TI  - Ictal and interictal respiratory changes in temporal lobe and absence epilepsy in
      childhood.
AB  - BACKGROUND: Autonomic dysfunctions occur during but also in between seizures.
      During seizures, the direct involvement of central autonomic control centers
      cause specific changes in heart rate and respiration. The pathophysiology of
      autonomic dysfunctions that are observed in the interictal period is more
      difficult to explain. These alterations are most likely due to changes in the
      epileptic network and/or to a lesser extent due to direct interictal spike
      activity disturbing central autonomic centers. The aim of our study is to
      investigate whether ictal and interictal respiratory changes do occur in temporal
      lobe and absence epilepsy in children. We hypothesize that the interictal
      autonomic changes are due to changes in the neuronal network, by studying
      epilepsy patients with normal interictal background EEG. METHODS: Ictal and
      interictal single-lead ECG signals were extracted from 24h video-EEG recordings
      in 10 children with refractory temporal lobe seizures, in 10 children with
      absence seizures with occasional interictal discharges and 10 control subjects.
      RR interval time series were calculated and respiration parameters were derived
      from the ECG signal. ECG-derived respiration (EDR) signals were computed and time
      and frequency domain parameters were extracted to characterize the respiratory
      function. RESULTS: In the ictal registrations we observed bradypnea in 10 out of
      the 12 recorded seizures from the temporal lobe. In absence seizures, we observed
      a variable ictal effect on respiratory rate. In the analysis of the interictal
      data, the most remarkable finding was the higher power in the low frequency band
      and lower power in the high frequency band of the EDR signals in patients with
      absence seizures compared to control subjects, indicating a shift of respiratory
      rate to the lower frequencies. CONCLUSION: In conclusion we found a uniform
      pattern in ictal respiratory changes in temporal lobe seizures, due to direct
      involvement of central respiratory centers. In absence epilepsy, we found a
      disturbed respiratory control in between seizures. These changes were not present
      in the patients with temporal lobe epilepsy. The observed interictal changes in
      respiration in absence epilepsy are most likely due to epileptogenetic changes in
      the thalamocortical network, involved in absence epilepsy and could not be
      explained by interictal spike activity.

PMID- 23948398
TI  - Health system performance comparison: new directions in research and policy.

PMID- 23948399
TI  - [The expressions of NLRP3 inflammasome and its downstream molecules in the mouse
      model of Helicobacter pylori infection].
AB  - OBJECTIVE: To study the expressions of NLRP3 inflammasome and its downstream
      molecules in the gastric tissues and sera of Helicobacter pylori (H.pylori)
      infected C57BL/6 mice, and to preliminary explore the role of NLRP3 inflammasome
      signalling pathway in the pathogenesis of H.pylori infection. METHODS: C57BL/6
      mice were randomly divided into H.pylori infection group and PBS control group,
      and mice were sacrificed at different time points after H.pylori infection. The
      mRNA expressions of NLRP3 inflammasome and downstream signalling pathway related
      molecules in mouse gastric tissues were detected by RT-PCR, and the protein level
      of caspase-1 was analyzed by Western blotting. The contents of IL-1beta, IL-18
      and IL-33 in the sera were measured with ELISA. RESULTS: Chronic inflammatory
      response was observed in the gastric mucosal tissues of H.pylori-infected mice
      and it gradually aggravated. Compared with the control mice, the mRNA expressions
      of NLRP3 inflammasome signalling pathway related molecules and the protein level
      of caspase-1 increased markedly in the gastric tissues of H.pylori-infected mice.
      Moreover, the contents of IL-1beta, IL-18 and IL-33 in the sera of H.pylori
      infected mice were also significantly elevated. CONCLUSION: NLRP3 inflammasome
      signalling pathway could be activated by H.pylori infection.

PMID- 23948400
TI  - [Role of PRNCR1 in the castration resistant prostate cancer].
AB  - OBJECTIVE: To investigate the role of long non-coding RNA prostate cancer non
      coding RNA1 (PRNCR1) in the castration resistant prostate cancer cells. METHODS:
      We compared the PRNCR1 mRNA expression of androgen-dependent prostate cancer
      cells LNCaP and androgen-independent prostate cancer cells C4-2 by real-time
      quantitative PCR (qRT-PCR). According to PRNCR1 gene sequence, siRNA fragments
      (PRNCR1-siRNA) were designed and synthesized to transfect C4-2 cells, and 48 h
      later, the expression of PRNCR1 mRNA was detected again by qRT-PCR to confirm the
      silence of PRNCR1. Thereafter, we determined the expression level of androgen
      receptor (AR) using Western blotting, and observed the change in the
      proliferation, apoptosis and invasion ability of C4-2 cells by means of MTT, flow
      cytometry and Transwell cell invasion assay, respectively. RESULTS: Compared with
      LNCaP cells, the expression level of PRNCR1 mRNA in C4-2 cells increased
      significantly. After transfected with PRNCR1-siRNA to silence the PRNCR1 mRNA
      expression, the C4-2 cells showed the inhibited expression of AR protein, the
      depressed proliferation and invasion abilities and the increased apoptosis rate.
      CONCLUSION: PRNCR1 may play an important role in the progression of castration
      resistant prostate cancer through mediating the expression of AR.

PMID- 23948401
TI  - [Effects of Gansu Dangshen decoction on the immune function of D-galactose
      induced aging mice].
AB  - OBJECTIVE: To study the effect of Chinese herb Dangshen decoction on the immune
      function of D-galactose-induced aging mice. METHODS: A total of 60 mice were
      randomly divided into 5 groups, namely normal control group, aging model group,
      high and low concentration Dangshen treated groups, vitamin E control group.
      Aging mice models were made by D-galactose. We weighed all mice, determined their
      indexes of the spleen and thymus, observed the ultrastructure of the spleen, and
      detected the expression of CD138 by immunohistochemistry. The levels of serum
      IgG, IgM and complement C3 and C4 were detected by ELISA. RESULTS: Compared with
      normal control group, the aging mice had lower indexes of the spleen and thymus
      (P<0.01). Compared with aging mice, the indexes rose significantly in Dangshen
      treated groups and vitamin E group (P<0.01). Furthermore, the lymphocytes of the
      spleen were injured obviously in the aging mice, but the ultrastructure of spleen
      got repaired in Dangshen treated groups and vitamin E group, especially high
      concentration Dangshen treated group that presented the lymphocytes nearly as
      normal as the normal control group. In addition, compared with the normal control
      group, the aging mice showed a lower expression of CD138 in the spleen(P<0.01),
      and the levels of IgG, IgM and complement C3 and C4 dropped sharply (P<0.01 or
      P<0.05). However, they were all significantly higher in the high concentration
      Dangshen group than in the aging mice (P<0.01 or P<0.05), and were not
      statistically different between the low concentration Dangshen group and the
      vitamin E group (P>0.05). CONCLUSION: The decoction of Chinese herb Dangshen in
      Gansu can enhance the immune function of D-galactoce-induced aging mice.

PMID- 23948402
TI  - [Therapeutic effect of allogenic bone marrow mesenchymal stem cell
      transplantation on EAE mouse].
AB  - OBJECTIVE: To investigate the therapeutic effect of allogenic bone marrow stem
      cells (BMSCs) transplantation on experimental autoimmune encephalomyelitis (EAE)
      and the underlying immunoregulatory mechanism. METHODS: EAE models were
      established by myelin oligodendrocyte glycoprotein (MOG) peptide immunization in
      C57BL/6J mice; BMSCs were purified and cultured from bone marrow of BALB/c mice,
      then transplanted to the EAE models. The scores of neurological function defect
      were assessed before and after BMSCs transplantation. The frequencies of
      CD4(+);CD25(+);Foxp3(+); T cells (Tregs) in mice lymph organs were measured by
      flow cytometry and the expressions of IL-2, IL-4, IL-17 and IL-23 mRNA in mouse
      spleen samples were detected by real-time quantitative RT-PCR after BMSCs
      transplantation. RESULTS: Transplantation of allogenic BMSCs improved the
      clinical score of the EAE mice. Compared with EAE control group, the frequencies
      of Tregs in spleen, lymph node and thymus of EAE mice transplanted with BMSCs
      increased significantly, and the levels of IL-2 and IL-17 mRNA significantly
      decreased, while IL-4 and IL-23 mRNA increased. CONCLUSION: Transplantation of
      allogenic BMSCs can prevent the development of EAE by regulating the frequency of
      Tregs and the levels of the cytokines secreted by CD4(+);T cells.

PMID- 23948403
TI  - [Effect of berberine hydrochloride on the proliferation, apoptosis and cytokine
      secretion of splenocytes in mice].
AB  - OBJECTIVE: To investigate the effect of berberine hydrochloride (BBR) on the
      proliferation, apoptosis, TNF-alpha, IL-2 and IFN-gamma secretion of splenocytes
      in mice. METHODS: The splenocytes isolated from the spleen of mice in a sterile
      environment were pretreated with BBR at the concentrations of 1, 2, 4 MUg/mL for
      60 min. Thereafter, the cells were stimulated with polyclonal activators ConA and
      cultured for 24, 48, 72 h, respectively. MTT assay was used to detect the
      proliferation of cells; flow cytometry was performed to detect the splenocyte
      apoptosis according to the fluorescence intensity of the splenocytes stained with
      PI and annexin V-FITC; the concentrations of TNF-alpha, IL-2 and IFN-gamma in the
      culture supernate was quantificationally analyzed by the ELISA. RESULTS: Compared
      with the control group, BBR within the concentration range above significantly
      inhibited the splenocyte proliferation, TNF-alpha, IL-2 and IFN-gamma secretion
      of the splenocytes activated by ConA in a dose- and time-dependent manner
      (P<0.05), but didn't significantly cause the apoptosis of splenocytes (P>0.05).
      CONCLUSION: BBR can have immunosuppressive influence on the splenocytes in mice
      and may act as a potential immunosuppressive drug.

PMID- 23948404
TI  - [The migration of CXCR4(+); BMSCs and the ox-LDL-induced injury in endothelial
      cells].
AB  - OBJECTIVE: To study whether the stromal cell-derived factor 1 (SDF-1) secreted by
      endothelial cells affects the CXCR4(+); stem cell migration. METHODS: CXCR4(+);
      bone marrow-derived mesenchymal stem cells (BMSCs) were isolated from mouse bone
      marrow. Human umbilical vein endothelial cells (HUVECs) were stimulated with
      oxidized low-density lipoprotein (ox-LDL), and the cell proliferation was
      detected by MTT assay, the expressions of SDF-1alpha mRNA and protein were
      detected by RT-PCR and ELISA, respectively. The migration of CXCR4(+); BMSCs was
      analyzed by Transwell(R); chamber assay. RESULTS: The stimulation of ox-LDL
      affected the proliferation and increased significantly the expression levels of
      SDF-1alpha mRNA and protein in HUVECs, and the medium supernatant promoted the
      migratory response of CXCR4(+); BMSCs. When the neutralizing CXCR4 antibody
      eliminated the secreted SDF-1alpha, the migratory activity markedly decreased.
      CONCLUSION: CXCR4(+); BMSCs might migrate to endothelial cells by SDF
      1alpha/CXCR4 axis in the atherosclerosis process.

PMID- 23948405
TI  - [Effect of autophagy inhibitor 3-methyladenine on proliferation and activation of
      hepatic stellate cells].
AB  - OBJECTIVE: To investigate the effect of autophagy inhibitor 3-methyladenine (3
      MA) on proliferation and activation of hepatic stellate cells (HSCs) and
      investigate the underlying molecular mechanism. METHODS: Cultured HSC-T6 cells
      were cultured in vitro and treated with different concentrations of 3-MA (low
      dose group, 2.5 mmol/L; middle-dose group, 5 mmol/L; high-dose group, 10 mmol/L;
      control group, 0 mmol/L). The mRNA expressions of alpha-SMA and type I collagen
      were determined by RT-PCR; the protein expressions of LC3II, a-SMA and type I
      collagen were detected by Western blotting; cell proliferation was observed by
      MTT assay and cell cycle by flow cytometry. RESULTS: The autophagy of HSC-T6
      cells decreased with the rising of the concentration of 3-MA. The mRNA
      expressions of alpha-SMA and type I collagen in all three 3-MA-treated groups
      were significantly down-regulated, compared with those in control group (P<0.05).
      Meanwhile, compared with the control group, the 3-MA-treated groups also showed
      significantly down-regulated protein expressions of LC3II, alpha-SMA, and type I
      collagen (P<0.05), significantly lower proliferation activity (P<0.05) and
      significantly higher numbers of HSCs in the G2 phase (P<0.05). CONCLUSION: The
      autophagy inhibitor 3-MA significantly down-regulated the expressions of LC3II,
      alpha-SMA and type I collagen in HSC-T6 and caused an arrest in the G2 phase of
      the cells, thus inhibiting the proliferation and activation of HSCs.

PMID- 23948406
TI  - [Role of Rab23 in invasion and migration of human breast cancer Bcap-37 cells].
AB  - OBJECTIVE: To investigate the effects of Rab23 over-expression and Rab23 knock
      out on the migration and invasion of breast cancer cell line Bcap-37. METHODS:
      Western blotting was employed to detect the expression of Rab23 in breast cell
      line HBL-100 and cancer cell lines Bcap-37, MDA-MB-231, and MCF-7. Lentiviral
      vectors with Rab23 genes and with Rab23 RNAi were respectively transfected into
      breast cancer cell line Bcap-37, and the cells presenting the stable over
      expression of Rab23 and the knock-out of Rab23 were respectively selected.
      Scratch healing assay and Transwell(R); invasion assay were used to examine the
      alterations of Bcap-37 cell migration and invasion potentials after Rab23 over
      expression and Rab23 knock-out. RESULTS: Western blotting indicated that Rab23
      was expressed in all breast cancer cell lines and normal breast cell line. And
      Rab23 expression level was the highest in Bcap-37 cells, which was statistically
      different as compared with HBL-100 cells (P<0.01). Compared with the control
      group, Bcap-37 cell line with Rab23 over-expression had the dramatically enhanced
      migration and invasion potentials (P<0.01). On the other hand, Bcap-37 cell line
      with Rab23 knock-out showed the significantly attenuated migration and invasion
      potentials (P<0.01). CONCLUSION: Rab23 plays a pivotal role in the migration and
      invasion of Bcap-37 cells.

PMID- 23948407
TI  - [Odontogenic differentiation of bone marrow-derived mesenchymal stem cells
      induced by periodontal ligament stem cells].
AB  - OBJECTIVE: To investigate the mechanism underlying the mechanism of odontogenic
      differentiation of bone marrow-derived mesenchymal stem cells (BMMSCs) induced by
      periodontal ligament stem cells (PDLSCs), and offer an experimental evidence for
      the combination of the two types of stem cells to make regenerative periodontal
      complex. METHODS: By means of Transwell(R); chamber, PDLSCs and BMMSCs from
      miniature pigs were co-cultured indirectly at different mixing ratios of PDLSCs
      to BMMSCs, 10:1 (group A), 1:1 (group B), 1:10 (group C). On the other hand,
      PDLSCs and BMMSCs were respectively cultured alone as positive and negative
      control group. Fourteen days later, the expressions of scleraxis, matrix
      extracellular phosphoglycoprotein (MEPE), osteocalcin (OCN), osterix (OSX) were
      detected by immunofluorescence and real-time quantitative PCR (qRT-PCR) to
      determine the optimal ratio of PDLSCs to BMMSCs for odontogenic differentiation.
      RESULTS: Immunofluorescence and qRT-PCR showed that the expression levels of
      sceleraxi, OCN and OSX protein and relative mRNA had no statistically significant
      difference in the A, B, C groups (P>0.05), but as for MEPE, its relative mRNA
      expression level in group A was significantly higher than that in group B or C
      (P<0.01). CONCLUSION: In the indirect co-culture of PDLSCs and BMMSCs, BMMSCs can
      obtain PDLSCs' biological characteristics to different extent, and meanwhile, a
      small number of PDLSCs can also induce the odontogenic differentiation of BMMSCs.

PMID- 23948408
TI  - [Preparation and identification of anti-follicle-stimulating hormone receptor
      nanobodies].
AB  - OBJECTIVE: To prepare camel derived nanobodies which specifically bind to
      follicle-stimulating hormone receptor (FSHR). METHODS: The FSHR gene fragment
      (fshr234) was expressed in E.coli as antigen for affinity screening against VHH
      phage display library constructed from Xinjiang Bactrian camel. After confirmed
      by DNA sequencing, the vhh gene fragments of interest were subcloned into pET30a
      expression vector, and then were used to transform E.coli BL21(DE3). After IPTG
      induction, 6*His and c-Myc tagged fusion nanobodies were expressed. The
      nanobodies were purified by Ni-ion affinity chromatography. The binding
      specificity of nanobodies with His-FSHR234 was determined by ELISA. RESULTS: By
      enrichment screening with the antigen His-FSHR234, the 28 clones showed VHH
      sequence identities in DNA sequencing from 40 randomly selected binding clones.
      The 4 clones were subcloned into pET30a vector and confirmed as expected size of
      inserts by PCR and endonuclease digestion. The 4 expressed and affinity purified
      recombinant nanobodies namely VHHFSHR;-06, VHHFSHR;-25, VHHFSHR;-30 and VHHFSHR;
      50 showed single band at Mr; 31 000, 26 000, 25 000 and 26 000 on SDS-PAGE,
      respectively. ELISA results showed that 4 nanobodies could bind to FSHR234
      specifically, in which VHHFSHR;-06 showed the highest antigen binding activity.
      CONCLUSION: By screening camel VHH phage display library with His-FSHR234
      antigen, one nanobody, VHHFSHR;-06 with relatively high antigen binding activity
      has been produced and identified.

PMID- 23948409
TI  - [Preparation of monoclonal antibodies against hFGF-21 and identification of
      epitope].
AB  - OBJECTIVE: To prepare monoclonal antibodies (mAbs) against human fibroblast
      growth factor 21 (hFGF-21), and identify the epitope of hFGF-21 mAb through
      bacterial display. METHODS: With hFGF-21 as an immunogen and detective antigen,
      we screened hybridoma cell lines secreting anti-hFGF-21 mAbs using indirect
      ELISA. The different fragments of hFGF-21 were cloned into bacterial display
      vector (Apex) to identify the epitope by fluorescence-activated cell sorting
      (FACS) using FITC-labeled mAbs. RESULTS: We obtained a stable hybridoma cell line
      secreting mAbs against hFGF-21; the heavy and light chains of the mAb were IgG 2b
      and Kappa, respectively. The ascites titer of the hybridoma cell line was
      1:4.096*10(6);. The cell line was stable after 30 passages or when stored in
      liquid nitrogen for 3 months. Western blotting showed the mAbs could bind to hFGF
      21 specifically, and could cross-react with murine FGF-21. FACS indicated that
      this antibody could bind to downstream 107-121 amino acids of hFGF-21.
      CONCLUSION: The mAbs against hFGF-21 we prepared showed high specificity and
      stability; the epitope of the mAbs was 107-121 amino acids of hFGF-21.

PMID- 23948410
TI  - [Preparation of polyclonal antibody to nucleoprotein from Xinjiang hemorrhagic
      fever virus and its immunological evaluation].
AB  - OBJECTIVE: To express and purify the nucleoprotein (NP) from Xinjiang hemorrhagic
      fever virus(XHFV) strain BA88166 in E.coli, and prepare and identify its
      polyclonal antibody. METHODS: The cDNA of S gene segment of BA88166 strain was
      amplified by RT-PCR and cloned into prokaryotic expression vector pET-32a to
      generate a recombinant plasmid named pET-88166S. The pET-88166S was transformed
      into E.coli BL21 (DE3). The NP-His fusion protein was induced by IPTG, purified
      by Ni-NTA purification system, and analyzed by SDS-PAGE. To prepare the
      antiserum, New Zealand white rabbits were immunized with the purified NP-His
      protein. The titer and specificity of the antiserum to NP were analyzed by ELISA
      and Western blotting, respectively. RESULTS: Restriction endonuclease analysis
      and DNA sequencing showed that the prokaryotic xpression vector of pET-88166S was
      constructed successfully. NP-His fusion protein was expressed in E.coli BL21
      (DE3) after IPTG induction and its relative molecular mass (Mr;) was about 66
      000. ELISA and Western blotting showed that the titers of the antisera were above
      1:25 600, and that the antisera can specifically bind with the entire and
      truncated NP protein of XHFV strain YL04057. CONCLUSION: NP-His fusion protein
      can be successfully expressed in E.coli and the specific anti-NP rabbit
      polyclonal antibody has been obtained, which will provide the basic information
      for the studies on the diagnosis, treatment and prevention of Xinjiang
      hemorrhagic fever.

PMID- 23948411
TI  - [Expression down-regulation of c-Cbl and Cbl-b genes in peripheral blood
      mononuclear cells from multiple myeloma patients].
AB  - OBJECTIVE: To investigate c-Cbl and Cbl-b gene expressions in peripheral blood
      mononuclear cells (PBMCs) from multiple myeloma (MM) patients. METHODS: SYBR(R);
      Green PCR technique was used to detect c-Cbl and Cbl-b gene expressions in PBMCs
      from 23 MM patients and 22 healthy individuals, and RT-PCR and DNA sequence
      analysis were performed to analyze the mutations of 7-10 exons of c-Cbl. RESULTS:
      The expression of c-Cbl gene in MM patients (median: 0.798%) significantly
      decreased as compared with that in healthy controls (median: 2.443%) (P<0.05).
      The expression of Cbl-b gene in MM patients (median: 0.714%) also dropped
      significantly as compared with that in healthy controls (median: 2.179%)
      (P<0.05). The 7-10 exons of c-Cbl gene had two different sizes of fragments in 2
      MM patients: 483 bp and 148 bp which were wild-type and deletion mutants type of
      c-Cbl gene. c-Cbl gene mutations were not found in all MM patients. CONCLUSION:
      The expressions of c-Cbl and Cbl-b genes in PBMCs from MM patients are down
      regulated.

PMID- 23948412
TI  - [Expression and function prediction of miR-618 in sputa and sera of patients with
      pulmonary tuberculosis].
AB  - OBJECTIVE: To measure the level of miR-618 in sputa and sera from the patients
      with pulmonary tuberculosis, determine the concentration of IL-13 which is a
      cytokine encoded by target gene of miR-618, and predict the function of miR-618
      with bioinformatics. METHODS: Sputum and serum samples were collected from the
      healthy controls and the patients with active pulmonary tuberculosis,
      respectively. Level of miR-618 was measured by nucleic acid hybridization and
      real-time quantitative RT-PCR(qRT-PCR). Concentration of IL-13 was determined by
      ELISA. Target genes of miR-618 were predicted with TargetSean, and GO annotation
      and biological pathway of the target genes were analyzed with DAVID database and
      BINGO of Cytoscape. RESULTS: Both hybridization and qRT-PCR results showed that
      level of miR-618 in both sputa and sera obviously decreased in the tuberculosis
      group compared to the control group (P<0.05). There was no statistical difference
      in IL-13 concentration between the tuberculosis group and the control group,
      however, it had an increasing tendency in the former. GO annotation of predicted
      target genes of miR-618 was enriched in biological processes such as regulation
      of transcription and molecular functions such as DNA binding (P<0.05). In KEGG
      pathway, the predicted target genes mostly existed in TGF-beta signaling pathway
      (P<0.05). CONCLUSION: Level of miR-618 in both sputa and sera was significantly
      lower in the tuberculosis group than that in the control group and predicted
      target genes of miR-618 were mainly involved in biological processes such as
      regulation of transcription and RNA metabolism.

PMID- 23948413
TI  - [CD28 expression on CD4(+);T cells and its relationship with IFN-gamma/IL-10
      ratio in patients with primary immune thrombocytopenia].
AB  - OBJECTIVE: To investigate CD28 expression on CD4(+);T cells and its relationship
      with IFN-gamma/IL-10 ration in patients with primary immune thrombocytopenia
      (ITP) before and after treatment. METHODS: The expression of CD4(+);CD28(+); was
      detected by flow cytometry, the levels of IFN-gamma and IL-10 were determined by
      double-antibody sandwich ELISA and platelet count was tested by blood cells
      automatical counter in peripheral blood of 30 patients with ITP before and after
      glucocorticoid treatment and 26 cases of normal controls. Then the correlations
      between the outcomes were analyzed. RESULTS: The expression of CD4(+);CD28(+); of
      ITP patients before treatment was higher than that of the normal control group
      (P<0.05), however, after treatment the expression between the two groups had no
      statistical difference (P>0.05). Compared with the control group, the ITP
      patients before treatment showed the significantly higher level of IFN-gamma and
      the significantly decreased level of IL-10, and the ratio of IFN-gamma/IL-10 was
      significantly raised (P<0.01); while ITP patients after treatment had no
      statistically significant difference in the above indexes from the normal
      controls (P>0.05). Moreover, CD4(+);CD28(+); was positively correlated with IFN
      gamma/IL-10 ratio (P<0.05), and was negatively correlated with platelet count in
      ITP patients before treatment (P<0.05). CONCLUSION: Co-stimulatory molecule
      CD4(+);CD28(+); was closely related with immune disorder of ITP. It maybe played
      a role in the pathogenesis of ITP through involving Th1 advantage state
      formation.

PMID- 23948414
TI  - [Analysis of CD4(+);T cell subsets in peripheral blood of patients with
      rheumatoid arthritis].
AB  - OBJECTIVE: To investigate the percentages of Treg, Th1, Th2, Th17 cells in
      peripheral blood of patients with rheumatoid arthritis (RA) of different stages
      and their roles in the disease process to explore their associations with the
      disease activity markers and antibody markers. METHODS: We enrolled 78 RA
      patients and 21 healthy controls in this study. Percentages of Treg, Th1, Th2,
      Th17 cells were analyzed by flow cytometry. RESULTS: Percentages of
      CD3(+);CD4(+);T cells and CD4(+);CD25(+);T cells increased in RA groups; compared
      with non-active RA group and control group, active RA group had the higher
      percentage of Treg; Th2 cells were less in non-active RA group compared with
      controls, but Th1, Th17 cells were not significantly different in the three
      groups. Correlation analysis showed that no relationship was observed between
      Th1, Th2, Th17, Treg cells and RA activity markers (ESR, CRP and PLT).
      CONCLUSION: The abnormality of CD4(+);T cell subsets may contribute to the
      development of RA disease.

PMID- 23948415
TI  - [The expression of CARD18 in apoptin-transfected gastric cancer cells and gastric
      adenocarcinoma tissues].
AB  - OBJECTIVE: To study the expression of caspase recruitment domain family member 18
      (CARD18) in apoptin-induced apoptosis of gastric cancer cells and its role in the
      development of gastric cancer. METHODS: After gastric cancer cells were
      transfected with apoptin, differentially expressed proteins between the apoptin
      expression SGC7901 group and the control group were seperated using two
      dimensional gel electrophoresis and identified using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and Mascot
      database (http: //www.matrixscience.com/). The expression level and location of
      CARD18 in 56 cases of gastric adenocarcinoma and adjacent cancer-free tissues
      were respectively detected by RT-PCR, Western blotting and immunohistochemistry
      to analyze the relationship between CARD18 and the clinical pathological
      characteristics. RESULTS: RT-PCR and Western blotting showed that the level of
      CARD18 mRNA and protein was down-regulated the most significantly after apoptin
      treatment. The expression of CARD18 in gastric adenocarcinoma tissues was
      significantly higher than that in adjacent cancer-free tissues (P<0.05), and it
      was proved that the CARD18 expression was related to the gastric cancer lymph
      node metastasis and TNM stage (P<0.05). CONCLUSION CARD18 may be both a promising
      marker for prognosis and a target protein for treatment of gastric cancer.

PMID- 23948417
TI  - [Changes and clinical significance of serum level of syndecan-4 protein in
      patients with chronic congestive heart failure].
AB  - OBJECTIVE: To detect serum level of syndecan-4 protein in patients with chronic
      congestive heart failure (CHF) and investigate its correlation with New York
      Heart Association (NYHA) class and echocardiographic parameters. METHODS: The
      concentration of serum syndecan-4 protein was measured by enzyme-linked
      immunosorbent assay (ELISA) in 40 patients with CHF and 40 healthy controls
      (NCD), respectively. The parameters such as left ventricle ejection fraction
      (LVEF), fraction shortening (FS), left ventricle end-diastolic diameter (LVDd),
      left ventricle end-systolic diameter (LVDs), left ventricle end-diastolic volume
      (LVEDV) and left ventricle end-systolic volume (LVESV) were detected by
      echocardiography in 40 patients of CHF. Meanwhile, the patients' cardiac function
      was graded according to NYHA class. RESULTS: The levels of serum syndecan-4
      protein significantly increased in CHF group as compared with control group
      (P<0.01). In CHF group, as the increased grading of NYHA cardiac function, the
      levels of serum syndecan-4 protein significantly increased (P<0.05). The more
      upgraded the NYHA grading, the higher level of serum syndecan-4 protein. In
      bivariate correlations analysis showed that the level of serum syndecan-4 protein
      was significantly negatively correlated with LVEF and FS (P<0.05) and was
      significantly positively correlated with LVDd, LVDs, LVEDV and LVESV,
      respectively (P<0.05). CONCLUSION: Serum syndecan-4 concentration significantly
      increased in CHF patients, and it was closely correlated with NYHA class and left
      ventricle function parameters, so the level of serum syndecan-4 protein may have
      an important value in detection and surveillance of CHF.

PMID- 23948416
TI  - [Expressions and clinical significance of OX40 and OX40L in peripheral blood of
      patients with primary Sjogren's syndrome].
AB  - OBJECTIVE: To investigate the expressions of costimulatory molecules OX40 and
      OX40L on peripheral blood mononuclear cells (PBMC) and their relationship with
      clinical characteristics of patients with primary Sjogren's syndrome (pSS).
      METHODS: Peripheral blood samples were collected from 51 pSS patients and 36
      healthy subjects (HC). The expressions of OX40 and OX40L on PBMC were detected by
      immunofluorescence and flow cytometry. In addition, we observed the changes in
      the levels of OX40 and OX40L after treatment in 11 patients with primary pSS and
      searched for the relationship between their expression levels and patients'
      clinical manifestations. RESULTS: The expression of OX40 on CD4(+);T cells in pSS
      patients was significantly higher than that in the HC group (8.65%+/-3.51% vs
      5.68%+/-1.68%, P<0.01). However, there was no significant difference in OX40
      expression on CD8(+);T cells between patient group and HC group. In comparison
      with HC group, the expression of OX40L on CD14(+); monocytes (6.76%+/-3.60% vs
      3.15%+/-1.89%, P<0.01) and CD19(+);B cells (4.69%+/-2.40% vs 2.76%+/-1.33%,
      P<0.01) significantly increased in pSS patients. Moreover, OX40 expression on
      CD4(+);T cells and OX40L expression on monocytes and B cells rose significantly
      in active pSS patients compared with those in inactive patients. The expression
      levels of OX40 and OX40L were higher in pSS patients with multiple system damage
      than in patients with simple exocrine gland injury. In addition,
      immunosuppressive therapy significantly reduced the expressions of OX40 and
      OX40L. CONCLUSION: The expressions of OX40 and OX40L on peripheral lymphocytes
      was upregulated in pSS patients. The high levels of OX40 and OX40L expression
      were significantly correlated with clinical outcome and therapeutic response,
      suggesting that OX40/OX40L pathway may play a critical role in pSS pathogenesis.

PMID- 23948418
TI  - [Differential expressions of MDR-1, RRM-1, EGFR and ERCC-1 in primary tumors and
      metastatic lymph nodes of NSCLC patients].
AB  - OBJECTIVE: To investigate the differential expressions of multidrug resistance
      protein 1 (MDR-1), ribonucleotide reductase M1(RRM-1), epidermal growth factor
      receptor(EGFR), excision repair cross-complementation group 1 (ERCC-1) in primary
      tumors and metastatic lymph nodes of patients with non-small cell lung cancer
      (NSCLC), and analyze the relationship between the differential expressions and
      pathological types of NSCLC. Methods The expressions of MDR-1, RRM-1, EGFR and
      ERCC-1 were detected by immunohistochemistry in primary tumors and metastatic
      lymph nodes of 46 cases NSCLC patients. Wilcoxon signed ranks test was used to
      compare the differences in the expressions of these four molecular markers in
      primary lesions and metastatic lymph nodes. Fisher's exact test was used to
      analyze the relationship between differential expressions and pathological types
      of NSCLC. RESULTS: The expressions of MDR-1, RRM-1, EGFR, ERCC-1 were observed in
      a variety of pathological types of NSCLC. The expression of ERCC-1 was
      significantly different between primary tumors and metastatic lymph nodes for
      lung adenocarcinoma (P=0.026). But the expressions of MDR-1, RRM-1, EGFR were not
      significantly different between primary tumors and metastatic lymph nodes for all
      pathological types of NSCLC (P>0.05). Conclusion The expression of MDR-1, RRM-1,
      EGFR, ERCC-1 of primary tumors and metastatic lymph nodes is found in all NSCLC.
      The expression of ERCC-1 is significantly different in primary tumors from in
      metastatic lymph nodes of lung adenocarcinoma.

PMID- 23948419
TI  - [Establishment of the dot immunoenzyme filtration assay for quantitative
      detection of estriol].
AB  - OBJECTIVE: To make anti-estriol (E3) monoclonal antibody (mAb) with high
      specificity, and develop a rapid, simple and sensitive method for the detection
      of E3 in county-level institutions. METHODS: The compounds of E3 were conjugated
      to horseradish peroxidase (HRP), bonine serum albumin (BSA) and ovalbumin (OVA)
      respectively by the method of active ester, and the hybridoma cell lines
      secreting specific anti-E3 mAb were developed via monoclonal antidody technology.
      The dot immunoenzyme filtration assay in competitive-inhibition format was
      established with nitrocellulose membrane as solid-phase carrier and anti-E3 mAb
      as coating antibody. RESULTS: 5 hybridoma cell lines secreting specific anti-E3
      mAb were obtained with E3-mAb titers in the range of 1*10(5); to 5*10(5); and the
      affinity constant (Ka) from 5.1*10(8); L/mol to 5.2*10(9); L/mol. The limit of
      detecting (LOD) value for E3 was 2 ng/mL and the detection range was 2-200 ng/mL.
      CONCLUSION: The dot immunoenzyme filtration assay with high-speed detection, easy
      accessibility and high sensitivity was successfully established.

PMID- 23948420
TI  - [Prokaryotic expression, purification and antigenicity identification of
      recombinant human survivin protein].
AB  - OBJECTIVE: To construct a prokaryotic expression plasmid pET28a-survivin,
      optimize the recombinant protein expression conditions in E.coli, and purify the
      survivin recombinant protein and identify its antigenicity. METHODS: Survivin
      cDNA segment was amplified by PCR and cloned into prokaryotic expression vector
      pET28a(+) to construct the recombinant expression vector pET28a-survivin. The
      expression vector was transformed into BL21 (DE3) and the fusion protein
      survivin/His was induced by IPTG. The fusion protein was purified through Ni
      affinity chromatography. The antigenicity of the purified survivin protein was
      identified by Western blotting and ELISA. RESULTS: The recombinant expression
      vector was verified successfully by BamHI and HindIII. The fusion protein induced
      by IPTG was obtained with Mr; about 24 000. The purity of the purified protein
      reached 90% by SDS-PAGE analysis. And the antigenicity of the survivin protein
      was validated by Western blotting and ELISA. CONCLUSION: The prokaryotic
      expression plasmid pET28a-survivin was successfully constructed and the survivin
      protein was expressed and purified in E.coli. The antigenicity of the purified
      survivin protein was demonstrated desirable.

PMID- 23948421
TI  - Systematic review: the safety of intra-articular corticosteroid injection prior
      to total knee arthroplasty.
AB  - BACKGROUND: Up to 30% of patients undergoing total knee arthroplasty (TKA) have
      received intra-articular corticosteroid injections prior to surgery. Debate
      exists as to whether such injections increase the rate of post-operative
      infection. Given that deep infection is a disastrous complication, a systematic
      review of the literature was undertaken to evaluate the safety of intra-articular
      corticosteroid injections given prior to TKA. Other features of corticosteroid
      use are also discussed including mechanism of action and optimal dosage. METHODS:
      Using PRISMA guidelines, EMBASE, CINAHL and MEDLINE databases were searched using
      the search terms 'total knee arthroplasty', 'replacement', 'corticosteroid',
      'steroid', 'infection', 'safety', and relevant articles critically appraised. The
      Newcastle-Ottawa Scale was used to assess for bias. RESULTS: No level one or two
      studies were available for review. Two retrospective case control studies and two
      cohort studies (level three evidence) which specifically evaluated the risk of
      infected TKA in association with pre-operative steroid injection were reviewed:
      three showed that prior steroid injection was not associated with increased
      infection rates; one article showed that prior steroid injection was associated
      with a significantly increased risk of deep infection post-TKA. CONCLUSION:
      Clinicians commonly administer steroid injections to patients who are candidates
      for TKA but may be unaware of the potential long term complications. The included
      studies were underpowered and at risk of selection bias and only one study
      demonstrated an increased risk of infection post-operatively. We recommend that
      further research is required to evaluate the safety of steroid injection prior to
      TKA. LEVEL OF EVIDENCE: III.

PMID- 23948422
TI  - Skeletal muscle atrophy during short-term disuse: implications for age-related
      sarcopenia.
AB  - Situations such as the recovery from injury and illness can lead to enforced
      periods of muscle disuse or unloading. Such circumstances lead to rapid skeletal
      muscle atrophy, loss of functional strength and a multitude of related negative
      health consequences. The elderly population is particularly vulnerable to the
      acute challenges of muscle disuse atrophy. Any loss of skeletal muscle mass must
      be underpinned by a chronic imbalance between muscle protein synthesis and
      breakdown rates. It is recognized that muscle atrophy during prolonged (>10 days)
      disuse is brought about primarily by declines in post-absorptive and post
      prandial muscle protein synthesis rates, without a clear contribution from
      changes in muscle protein breakdown. Few data are available on the impact of
      short-term disuse (<10 days) on muscle protein turnover in humans. However,
      indirect evidence indicates that considerable muscle atrophy occurs during this
      early phase, and is likely attributed to a rapid increase in muscle protein
      breakdown accompanied by the characteristic decline in muscle protein synthesis.
      Short-term disuse atrophy is of particular relevance in the development of
      sarcopenia, as it has been suggested that successive short periods of muscle
      disuse, due to sickness or injury, accumulate throughout an individual's lifespan
      and contributes considerably to the net muscle loss observed with aging. Research
      is warranted to elucidate the physiological and molecular basis for rapid muscle
      loss during short periods of disuse. Such mechanistic insight will allow the
      characterization of nutritional, exercise and/or pharmacological interventions to
      prevent or attenuate muscle loss during periods of disuse and therefore aid in
      the treatment of age-related sarcopenia.

PMID- 23948423
TI  - The 2nd International Standard for Interleukin-2 (IL-2). Report of a
      collaborative study.
AB  - Two candidate preparations of human sequence recombinant Interleukin-2 (IL-2)
      were formulated and lyophilized at NIBSC prior to evaluation in a collaborative
      study for their suitability to serve as a replacement international standard. The
      preparations were tested by eight laboratories using in vitro bioassays and
      immunoassays. The candidate preparation 86/500 was judged suitable to serve as a
      replacement international standard based on the data obtained for activity and
      stability. On the basis of the results reported here, the preparation coded
      86/500 was established by the WHO Expert Committee on Biological Standardisation
      (ECBS) in 2012 as the WHO 2nd IS for human IL-2 with an assigned value for IL-2
      activity of 210IU/ampoule. Calibration of the 2nd IS is primarily based on the
      bioassay in use in various laboratories and relies exclusively on the estimates
      calculated relative to the WHO 1st IS for continuity of the IU. 

PMID- 23948424
TI  - Next-generation transcriptome profiling reveals insights into genetic factors
      contributing to growth differences and temperature adaptation in Australian
      populations of barramundi (Lates calcarifer).
AB  - Identification of genetically-regulated adaptation in fish is a precursor to
      understanding how populations will respond to future climate induced stressors
      like temperature. Australian populations of barramundi (Lates calcarifer) show
      strong evidence of local adaptation to temperature. However, the phenotypic
      consequences of this adaptation are unknown and the genetic mechanisms underlying
      this response are poorly understood. In the current study, two populations of
      barramundi from temperature extremes of the species Australian distribution were
      communally reared at cool (22 degrees C), control (28 degrees C) and hot (36
      degrees C) water temperatures for 3.5months. Southern populations of barramundi
      originating from a cooler environment grew significantly faster at 22 degrees C
      than northern populations of warm adapted barramundi. However, no difference in
      population growth was present at either 28 degrees C or 36 degrees C. The
      underlying transcriptome profile of barramundi was examined via Illumina mRNA
      deep sequencing to determine the major contributing gene categories giving rise
      to phenotypic differences in barramundi population growth. Gene ontology (GO)
      analysis revealed enrichment in categories relating to the regulation of
      peptidase activity as well as microtubule, cytoplasmic and cellular metabolic
      based processes. Further analysis of the GO category "microtubule based process"
      with associated genes from the "response to stress" category revealed an apparent
      re-organization of cytoskeletal elements in response to an induced cold stress in
      northern barramundi reared at 22 degrees C, when compared with northern
      barramundi reared at 36 degrees C. Between southern barramundi and northern
      barramundi reared at 36 degrees C, an analysis of the "endopeptidase inhibitor
      activity" GO category in conjunction with stress genes indicated a suppression of
      the complement system in southern barramundi along with an increase in the
      cellular stress response. The results of the present study show that southern
      populations of barramundi exhibit underlying molecular adaptation to cooler water
      temperatures, but still retain a tolerance for warm water temperatures.
      Furthermore, GO profiling has revealed groups of genes that underlie population
      differences in temperature tolerance as a means to prioritize the analysis of
      differential gene expression in studies of local adaptation in the future. 

PMID- 23948425
TI  - Outcomes from magnetic resonance imaging-confirmed symptomatic cervical disk
      herniation patients treated with high-velocity, low-amplitude spinal manipulative
      therapy: a prospective cohort study with 3-month follow-up.
AB  - OBJECTIVE: The purpose of this study was to investigate outcomes of patients with
      cervical radiculopathy from cervical disk herniation (CDH) who are treated with
      spinal manipulative therapy. METHODS: Adult Swiss patients with neck pain and
      dermatomal arm pain; sensory, motor, or reflex changes corresponding to the
      involved nerve root; and at least 1 positive orthopaedic test for cervical
      radiculopathy were included. Magnetic resonance imaging-confirmed CDH linked with
      symptoms was required. Baseline data included 2 pain numeric rating scales
      (NRSs), for neck and arm, and the Neck Disability Index (NDI). At 2 weeks, 1
      month, and 3 months after initial consultation, patients were contacted by
      telephone, and the NDI, NRSs, and patient's global impression of change data were
      collected. High-velocity, low-amplitude spinal manipulations were administered by
      experienced doctors of chiropractic. The proportion of patients responding
      "better" or "much better" on the patient's global impression of change scale was
      calculated. Pretreatment and posttreatment NRSs and NDIs were compared using the
      Wilcoxon test. Acute vs subacute/chronic patients' NRSs and NDIs were compared
      using the Mann-Whitney U test. RESULTS: Fifty patients were included. At 2 weeks,
      55.3% were "improved," 68.9% at 1 month and 85.7% at 3 months. Statistically
      significant decreases in neck pain, arm pain, and NDI scores were noted at 1 and
      3 months compared with baseline scores (P < .0001). Of the subacute/chronic
      patients, 76.2% were improved at 3 months. CONCLUSIONS: Most patients in this
      study, including subacute/chronic patients, with symptomatic magnetic resonance
      imaging-confirmed CDH treated with spinal manipulative therapy, reported
      significant improvement with no adverse events.

PMID- 23948426
TI  - The effect of core stability exercises on variations in acceleration of trunk
      movement, pain, and disability during an episode of acute nonspecific low back
      pain: a pilot clinical trial.
AB  - OBJECTIVE: The purpose of this preliminary study was demonstrate if it was
      feasible to evaluate variations in acceleration of trunk movement, pain, and
      disability during an episode of acute nonspecific low back pain comparing regular
      trunk exercises to regular exercises in addition to core stability exercises.
      METHODS: A pilot randomized controlled trial was used to evaluate 33 participants
      recruited from a National Health Service physiotherapy musculoskeletal provider
      in the London district of Hillingdon. Participants were allocated to 2 groups; a
      regular exercise group (male, 2; female, 15) with a mean (SD) age of 35.8 (9.1)
      years and intervention group (male, 3; female, 13) with a mean (SD) age of 36.2
      (9.8) years. The regular exercise group received exercise that consisted of a
      core stability class including both specific and global trunk exercises. The
      intervention group, in addition to these core exercises, received further
      instruction on 8 specific stabilization muscles involving the transversus
      abdominis and the lumbar multifidus. Trunk sagittal acceleration, pain, and
      disability were measured using a Lumbar Motion Monitor, pain visual analog scale,
      and Roland Morris Disability Questionnaire, respectively. Measures were taken at
      baseline, 3 and 6 weeks, and a 3-month follow-up. Multiple regression with
      adjustment for baseline value was used to analyze each outcome. All outcomes were
      log transformed to correct skewness and so presented as ratio of geometric means
      with 95% confidence interval. RESULTS: Differences in mean trunk sagittal
      acceleration between the regular exercise and intervention groups was not
      statistically significant at any time point (ratio of means [95% confidence
      interval]: 3 weeks 1.2 [0.9-1.6], P = .2; 6 weeks 1.1 [0.8-1.5], P = .7; 3
      months: 1.2 [0.8-1.9], P = .9). Similarly, the effects on neither pain score nor
      disability score were significant (pain score: 3 weeks 1.3 [0.8-2.2], P = .3); 6
      weeks 1.2 [0.7-2.0], P = .6; 3 months 1.0 [0.5-1.9], P = 1.0); disability score:
      6 weeks 1.0 [0.7-1.5], P = 1.0; 3 months 1.3 [0.8-1.9], P = .3). Outcome measures
      for both groups improved over time. CONCLUSIONS: This pilot study demonstrated
      that a study of this nature is feasible. Both the regular exercise and the
      intervention groups demonstrated improvements in mean trunk sagittal acceleration
      at 3, 6, and 12 weeks. The preliminary findings showed that evidence was
      inconclusive for the beneficial effect of adding specific core stability
      exercises for acute low back pain. The results of this study demonstrated an
      increase in acceleration accompanied by a reduction in pain, which may suggest
      that acute nonspecific low back pain may induce the pain-spasm-pain model rather
      than the pain adaptation model.

PMID- 23948427
TI  - [Pain management in radiation oncology].
AB  - The goal of this article is to propose some practical means of pain management in
      radiation departments. Pain management in radiation oncology is difficult because
      of the high proportion of painful patients, underestimation by medical teams, and
      limited therapeutic options. Pain can cause mobilization difficulties, set-up
      errors, treatment interruption. According to procedure steps, a preventive
      attitude (for pre-radiation consultation) or an active attitude (for treatment)
      to quickly relieve the patient can be planned. This work is a brain storming
      about pain management. It is not a review about analgesic radiotherapy. The
      practical situations apply to patients to whom radiotherapy is indicated.
      Teamwork and anticipation are keywords to relieve patients. All proposed means
      are not always available for different reasons (time, finance, staff, training).
      The idea is to establish simple procedures that are appropriate to each center to
      fluidify acts, to optimize time for a successful irradiation. 

PMID- 23948428
TI  - Which renal vascular hypertension was induced.

PMID- 23948429
TI  - Furosemide for your mother?

PMID- 23948430
TI  - Unravelling parasitic nematode natural history using population genetics.
AB  - The health and economic importance of parasitic nematodes cannot be overstated.
      Moreover, they offer a complex and diverse array of life strategies, raising a
      multitude of evolutionary questions. Researchers are applying population genetics
      to parasitic nematodes in order to disentangle some aspects of their life
      strategies, improve our knowledge about disease epidemiology, and design control
      strategies. However, population genetics studies of nematodes have been
      constrained due to the difficulty in sampling nematodes and developing molecular
      markers. In this context, new computational and sequencing technologies represent
      promising tools to investigate population genomics of parasitic, non-model,
      nematode species in an epidemiological context. 

PMID- 23948431
TI  - IRONy OF FATE: role of iron-mediated ROS in Leishmania differentiation.
AB  - The protozoan parasite Leishmania experiences extreme environmental changes as it
      alternates between insect and mammalian hosts. In some species, differentiation
      of insect promastigotes into mammalian-infective amastigotes is induced by
      elevated temperature and low pH, conditions found within macrophage
      parasitophorous vacuoles (PVs). However, the signaling events controlling
      amastigote differentiation remain poorly understood. Recent studies revealed a
      novel role for iron uptake in orchestrating the differentiation of amastigotes,
      through a mechanism that involves production of reactive oxygen species (ROS) and
      is independent from pH and temperature changes. ROS are generally thought to be
      deleterious for pathogens, but it is becoming increasingly apparent that they can
      also function as signaling molecules regulating Leishmania differentiation, in a
      process that is tightly controlled by iron availability. 

PMID- 23948433
TI  - Identification and functional implication of nuclear localization signals in the
      N-terminal domain of JMJD5.
AB  - JMJD5 has recently been reported to participate in circadian rhythm regulation,
      embryological development, osteoclastogenesis and tumorigenesis. Although JMJD5
      has been found mainly localized in the nucleus of cells, how it enters the
      nucleus remains unclear. Here we report that JMJD5 contains a functional
      bipartite nuclear localization signal (NLS) and a chromosome region maintenance 1
      (CRM1)-dependent nuclear export signal (NES). Importin alpha/beta and transportin
      1 were further identified as JMJD5-associated transport proteins, and different
      binding regions were determined for the two nuclear import receptors.
      Additionally, we demonstrate that both the active NLS and the JmjC domain of
      JMJD5 are necessary for cyclin A1 transcription. Chromatin immunoprecipitation
      (ChIP) analysis confirmed the alterations of di-methylated lysine 36 of histone
      H3 (H3K36me2) in the coding region of cyclin A1. These results reveal that the N
      terminal domain is essential for the nuclear localization of JMJD5 and its normal
      enzymatic function towards substrates in the nucleus.

PMID- 23948432
TI  - Monitoring antifolate resistance in intermittent preventive therapy for malaria.
AB  - Mutations in the Plasmodium falciparum genes Pfdhfr and Pfdhps have rendered
      sulfadoxine-pyrimethamine (SP) ineffective for malaria treatment in most regions
      of the world. Yet, SP is efficacious as intermittent preventive therapy in
      pregnant women (IPTp) and infants (IPTi) and as seasonal malaria control in
      children (SMC). SP-IPTp is being widely implemented in sub-Saharan Africa. SP
      IPTi is recommended where the prevalence of SP-resistant malaria parasites is
      low, whereas SMC is recommended for areas of intense seasonal malaria
      transmission. The continuing success of these interventions depends largely on
      the prevalence of Pfdhfr and Pfdhps resistance mutations in the target
      population. Here we review the relationship between resistance mutations and SP
      IPT within target populations in the context of monitoring and informing
      implementation of this intervention. 

PMID- 23948434
TI  - Comprehensive overview of recent preparation and application trends of various
      open tubular capillary columns in separation science.
AB  - Open tubular (OT) capillary columns have been increasingly used in a variety of
      fields of separation science such as CEC, LC, and SPE. Especially their
      application in CEC has attracted a lot of attention for their outstanding
      separation performance. Various forms of OT stationary phase materials have been
      employed such as in-situ prepared polymers, molecular imprinted polymers (MIPs),
      brush ligands, host ligands, block copolymers, aptamers, carbon nanotubes,
      polysaccharides, proteins, tentacles, nanoparticles, monoliths, and
      polyelectrolyte multi-layers. They have been prepared either in the chemically
      bound format or physically adsorbed format. Sol-gel technologies and
      nanoparticles have been sometimes involved in their preparation. There have been
      also some unique miscellaneous studies, for example, adopting preferentially
      adsorbed mobile phase components as stationary phases. In this review, recent
      progresses since mostly 2007 will be critically discussed in detail with some
      summarized descriptions for the work before the date. 

PMID- 23948435
TI  - V876E mutation in CACNA1S gene associated with severe hypokalemic periodic
      paralysis in a Chinese woman.

PMID- 23948436
TI  - Long term serious olfactory loss in colds and/or flu.
AB  - INTRODUCTION: In the general population, we can find 2-3% of lifelong olfactory
      disorders (from hyposmia to anosmia). Two of the most frequent aetiologies are
      the common cold and flu. The aim of this study was to show the degree of long
      term olfactory dysfunction caused by a cold or flu. METHODS: This study was based
      on 240 patients, with olfactory loss caused only by flu or a cold. We excluded
      all patients with concomitant illness (66 patients), the rest of patients (n=174)
      consisted of 51 men (29.3%) and 123 women (70.7%). They all underwent
      olfactometry study (i and v cranial nerve) and a nasal sinus computed tomography
      scan, as well as magnetic resonance imaging of the brain. Results were compared
      with a control group (n=120). RESULTS: Very significant differences in levels of
      olfactory impairment for the olfactory nerve (P<.00001) and trigeminal nerve
      (P<.0001) were confirmed. CONCLUSIONS: People that suffer olfactory dysfunction
      for more than 6 months, from flu or a cold, present serious impairment of
      olfactory abilities.

PMID- 23948437
TI  - Balancing toxicity and efficacy: learning from trials and treatment using
      antiresorptive therapy in prostate cancer.

PMID- 23948438
TI  - Fenton-like application to pretreated cheese whey wastewater.
AB  - Cheese whey wastewater has been treated by the Fenton-like oxidation system after
      being pre-processed through a coagulation - flocculation stage with FeCl3 or
      alternatively, through a sedimentation step with Ca(OH)2 plus aerobic digestion.
      In the first case, Fenton-like oxidation is capable of reducing the initial COD
      (chemical oxygen demand) to 80% of the initial value, 20% of COD shows
      recalcitrance to chemical oxidation regardless of the operating conditions used.
      In the second case, the oxidation system is capable of removing almost the total
      COD present in the pretreated effluent. Given the lower values of initial COD,
      complete COD conversion is achieved at short reaction times within minutes
      depending on the initial reagent concentration. Removal of Fe(III) from the
      oxidation treatment can be achieved by Ca(OH)2 addition. Sedimentation pH
      significantly affects the observed settling rate. Hence, neutral conditions lead
      to better results than slightly acidic pHs. 

PMID- 23948439
TI  - The implications of new forest tenure reforms and forestry property markets for
      sustainable forest management and forest certification in China.
AB  - This study examines issues existing in the southern collective forests in China,
      particularly prior to the implementation of new forest tenure reforms, such as
      continued illegal logging and timber theft, inadequate availability of finance
      and inconsistent forest-related policies. Such problems are believed to be
      hindering the adoption of sustainable forest management (SFM) and forest
      certification by forest farmers in China. Two strategies were introduced by the
      Chinese government with the purpose of addressing these issues, namely forest
      tenure reforms and their associated supporting mechanism, forestry property
      markets. Through two case studies in southern China, we investigated the
      effectiveness of the two strategies as well as their implications for the
      adoption of SFM and forest certification. The two cases were Yong'an in Fujian
      province and Tonggu in Jiangxi province. Personal interviews with open-ended
      questions were conducted with small-scale forest farmers who had already
      benefited from the two strategies as well as market officers working for the two
      selected forestry property markets. The study identified eight issues
      constraining the potential adoption of SFM and certification in China, including
      limited finance, poorly developed infrastructure and transport systems, insecure
      forest tenures, inconsistent forest policies, low levels of awareness, illegal
      forest management practices, lack of local cooperative organizations, and
      inadequate knowledge and technical transfer. We found that the new forest tenure
      reforms and forestry property markets had generally fulfilled their original
      objectives and had the capacity to assist in addressing many of the issues facing
      forests prior to the reforms. 

PMID- 23948441
TI  - A new technique for the strengthening of aluminum tungsten inert gas weld metals:
      using carbon nanotube/aluminum composite as a filler metal.
AB  - The effect of multi-walled carbon nanotube (MWCNT) on the mechanical properties
      of aluminum multipass weld metal prepared by the tungsten inert gas (TIG) welding
      process was investigated. High energy ball milling was used to disperse MWCNT in
      the aluminum powder. Carbon nanotube/aluminum composite filler metal was
      fabricated for the first time by hot extrusion of ball-milled powders. After
      welding, the tensile strength, microhardness and MWCNT distribution in the weld
      metal were investigated. The test results showed that the tensile strength and
      microhardness of weld metal was greatly increased when using the filler metal
      containing 1.5 wt.% MWCNT. Therefore, according to the results presented in this
      paper, it can be concluded that the filler metal containing MWCNT can serve as a
      super filler metal to improve the mechanical properties of TIG welds of Al and
      its alloys.

PMID- 23948440
TI  - Multivitamin supplementation improves haematologic status in children born to HIV
      positive women in Tanzania.
AB  - INTRODUCTION: Anaemia is prevalent among children born to HIV-positive women, and
      it is associated with adverse effects on cognitive and motor development, growth,
      and increased risks of morbidity and mortality. OBJECTIVE: To examine the effect
      of daily multivitamin supplementation on haematologic status and mother-to-child
      transmission (MTCT) of HIV through breastfeeding. METHODS: A total of 2387
      infants born to HIV-positive women from Dar es Salaam, Tanzania were enrolled in
      a randomized, double-blind, placebo-controlled trial, and provided a daily oral
      supplement of multivitamins (vitamin B complex, C and E) or placebo at age 6
      weeks for 24 months. Among them, 2008 infants provided blood samples and had
      haemoglobin concentrations measured at baseline and during a follow-up period.
      Anaemia was defined as haemoglobin concentrations <11 g/dL and severe anaemia
      <8.5 g/dL. RESULTS: Haemoglobin concentrations among children in the treatment
      group were significantly higher than those in the placebo group at 12 (9.77 vs.
      9.64 g/dL, p=0.03), 18 (9.76 vs. 9.57 g/dL, p=0.004), and 24 months (9.93 vs.
      9.75 g/dL, p=0.02) of follow-up. Compared to those in the placebo group, children
      in the treatment group had a 12% lower risk of anaemia (hazard ratio (HR): 0.88;
      95% CI: 0.79-0.99; p=0.03). The treatment was associated with a 28% reduced risk
      of severe anaemia among children born to women without anaemia (HR: 0.72; 95% CI:
      0.56-0.92; p=0.008), but not among those born to women with anaemia (HR: 1.10;
      95% CI: 0.79-1.54; p=0.57; p for interaction=0.007). One thousand seven hundred
      fifty three infants who tested HIV-negative at baseline and had HIV testing
      during follow-up were included in the analysis for MTCT of HIV. No association
      was found between multivitamin supplements and MTCT of HIV. CONCLUSIONS:
      Multivitamin supplements improve haematologic status among children born to HIV
      positive women. Further trials focusing on anaemia among HIV-exposed children are
      warranted in the context of antiretroviral therapy.

PMID- 23948442
TI  - Modelling of tumour growth and cytotoxic effect of docetaxel in xenografts.
AB  - One of the major sources of information on physiological and pathophysiological
      effects in pre-clinical oncology studies is the xenografted tumour animal model.
      However, measurement of tumour volume over time potentially masks a range of
      biological changes that the xenograft is undergoing. In this paper a mechanistic
      model of tumour growth in xenografts is presented that can be used to investigate
      the mode of drug action with respect to phenotypic changes. The model
      encapsulates key histological biomarkers and spatial constraints. The unknown
      model parameters are first shown to be uniquely identifiable from the proposed
      experimental studies, and then estimated from the resulting data using the anti
      cancer agent docetaxel. 

PMID- 23948443
TI  - Clinical impact of aspartyl aminopeptidase expression and activity in colorectal
      cancer.
AB  - Aspartyl aminopeptidase (ASP; EC 3.4.11.21) is a widely distributed and abundant
      cytosolic enzyme that regulates bioactive peptides such as angiotensin II. It has
      been demonstrated that the expression and activity of this enzyme is modified in
      tissue and serum of patients with several types of cancer. However, the
      involvement of ASP in the neoplastic development and survival of patients with
      colorectal cancer (CRC) has not been analyzed to date. The activity and messenger
      RNA expression of ASP in tumor tissue (n = 71) and plasma (n = 40) of patients
      with CRC was analyzed prospectively using fluorometric and quantitative real-time
      polymerase chain reaction methods. Data obtained from tumor tissue were compared
      with those from the surrounding normal mucosa. Classic pathologic parameters
      (grade, stage, nodal invasion, distant metastases and perineural, lymphatic, and
      vascular invasion) were stratified following ASP data and analyzed for 5-year
      survival. ASP was upregulated in CRC tissues, and greater activity correlated
      significantly with the absence of lymph node metastases and with better overall
      survival. Inversely, greater plasmatic ASP activity was associated with worse
      overall and disease-free survival. Data suggest that ASP is involved in
      colorectal neoplasia and point to this enzyme as a potential useful diagnostic
      tool in clinical practice. 

PMID- 23948444
TI  - Changes in the management of benign liver tumors.

PMID- 23948445
TI  - Six years of follow-up after bilateral hand replantation.
AB  - Replantation is the gold standard surgical treatment of amputations of the upper
      limb; however, this demanding procedure is not always preformed in bilateral limb
      amputation. The objective of this study was to analyze, six years after surgery,
      the sensorimotor recovery of both replanted hands. A 21-year-old patient with
      bilateral hand amputation was benefited from limb replantation. Surgery included
      debridement of the amputated hands and recipient's stumps, bone fixation,
      arterial and venous anastomoses, nerve sutures, tendon sutures and skin closure.
      Rehabilitation program included physiotherapy, electrostimulation and
      occupational therapy. Sensory and motor evaluation was performed 6 years after
      replantation. At 6 years, the patient presented a good/satisfactory recovery of
      range of motion and strength, better at right hand. The patient was able to
      perform right thumb opposition. Static two-point discrimination was 20mm,
      sensitivity to pain and thermal stimuli and ability to sweat were present on both
      hands. Reinnervation was confirmed by electromyography. Functional recovery was
      higher at the right hand when compared to the left hand. He was highly satisfied
      with the result of surgery for right hand and fairly satisfied with the result
      for left hand. He was able to return to a secretary work 16 months after the
      accident. A proper functional result can be accomplished with bilateral hand
      replantation.

PMID- 23948446
TI  - Marked variation in delivery room management in very preterm infants.
AB  - BACKGROUND: The International Liaison Committee on Resuscitation (ILCOR) and U.K.
      Resuscitation Council (UKRC) updated guidance on newborn resuscitation in late
      2010. OBJECTIVES: To describe delivery room (DR) practice in stabilisation
      following very preterm birth (<32 weeks gestation) in the U.K. METHODS: We
      emailed a national survey of current DR stabilisation practice of very preterm
      infants to all U.K. delivery units and conducted telephone follow-up calls.
      RESULTS: We obtained 197 responses from 199 units (99%) and complete data from
      186 units. Tertiary units administered surfactant in the DR (93% vs. 78%,
      P=0.01), instituted DR CPAP (77% vs. 50%, P=0.0007), provided PEEP in the
      delivery room (91% vs. 69%, P=0.0008), and started resuscitation in air or
      blended oxygen (91% vs. 78%, P=0.04) more often than non-tertiary units. Routine
      out of hours consultant attendance at very preterm birth was more common in
      tertiary units (82% vs. 55%, P=0.0005). CONCLUSIONS: Marked variation in DR
      stabilisation practice of very preterm infants persisted one year after the
      publication of revised UKRC guidance. Delivery room care provided in non-tertiary
      units was less consistent with current international guidance.

PMID- 23948447
TI  - A pilot study examining the role of regional cerebral oxygen saturation
      monitoring as a marker of return of spontaneous circulation in shockable (VF/VT)
      and non-shockable (PEA/Asystole) causes of cardiac arrest.
AB  - BACKGROUND: Non-invasive monitoring of cerebral perfusion and oxygen delivery
      during cardiac arrest is not routinely utilized during cardiac arrest
      resuscitation. The objective of this study was to investigate the feasibility of
      using cerebral oximetry during cardiac arrest and to determine the relationship
      between regional cerebral oxygen saturation (rSO2) with return of spontaneous
      circulation (ROSC) in shockable (VF/VT) and non-shockable (PEA/asystole) types of
      cardiac arrest. METHODS: Cerebral oximetry was applied to 50 in-hospital and out
      of-hospital cardiac arrest patients. RESULTS: Overall, 52% (n=26) achieved ROSC
      and 48% (n=24) did not achieve ROSC. There was a significant difference in mean+/
      SD rSO2% in patients who achieved ROSC compared to those who did not (47.2+/
      10.7% vs. 31.7+/-12.8%, p<0.0001). This difference was observed during asystole
      (median rSO2 (IQR) ROSC versus no ROSC: 45.0% (35.1-48.8) vs. 24.9% (20.5-32.9),
      p<0.002) and PEA (50.6% (46.7-57.5) vs. 31.6% (18.8-43.3), p=0.02), but not in
      the VF/VT subgroup (43.7% (41.1-54.7) vs. 42.8% (34.9-45.0), p=0.63).
      Furthermore, it was noted that no subjects with a mean rSO2<30% achieved ROSC.
      CONCLUSIONS: Cerebral oximetry may have a role as a real-time, non-invasive
      predictor of ROSC during cardiac arrest. The main utility of rSO2 in determining
      ROSC appears to apply to asystole and PEA subgroups of cardiac arrest, rather
      than VF/VT. This observation may reflect the different physiological factors
      involved in recovery from PEA/asytole compared to VF/VT. Whereas in VF/VT,
      successful defibrillation is of prime importance, however in PEA and asytole
      achieving ROSC is more likely to be related to the quality of oxygen delivery.
      Furthermore, a persistently low rSO2 <30% in spite of optimal resuscitation
      methods may indicate futility of resuscitation efforts.

PMID- 23948448
TI  - Neoadjuvant therapy reduces the incidence of nodal micrometastases in esophageal
      adenocarcinoma.
AB  - BACKGROUND: We evaluated the impact of neoadjuvant chemoradiotherapy (CRT) on
      nodal micrometastases (NMMs) in esophageal adenocarcinoma (EAC) patients with
      histologically negative nodes ([y]pN0). METHODS: Of 48 consecutively treated
      patients with neoadjuvant CRT, we selected 20 EAC ypN0 patients (group 1). These
      patients were matched with 20 pN0 EAC patients who had surgery alone (group 2).
      Harvested (y)pN0 lymph nodes were examined immunohistochemically (anti-CK8/18
      [CAM 5.2]) according to a validated sentinel node protocol. A 3rd group (n = 11)
      staged as ypN1 after neoadjuvant CRT was used as the control group. RESULTS:
      Upstaging to NMM+ occurred in 2 patients (10%) in group 1 and in 8 patients (40%)
      in group 2 (P = .028). Disease-free and overall survival rates in NMM+ patients
      in group 1 were worse compared with NMM- patients (P = .014 and P = .003,
      respectively) but comparable with ypN1 patients (n = 11). CONCLUSIONS: A 30%
      reduction of NMM+ was obtained after neoadjuvant treatment in (y)pN0 patients.
      NMM+ after CRT had a negative impact on survival in ypN1 patients. These data
      warrant further investigation in larger prospective datasets.

PMID- 23948449
TI  - Twelve years of MSOME and IMSI: a review.
AB  - A promising method for observing spermatozoa, motile sperm organelle morphology
      examination (MSOME) enables the evaluation of the nuclear morphology of motile
      spermatozoa in real time at high magnification and has allowed the introduction
      of a modified microinjection procedure, intracytoplasmic morphologically selected
      sperm injection (IMSI). Since its development, several studies have intensively
      investigated the efficacy of MSOME and IMSI. The objective of the present study
      is to review the current literature on the MSOME and IMSI techniques. A promising
      method for observing spermatozoa, motile sperm organelle morphology examination
      (MSOME), enables the evaluation of the nuclear morphology of motile spermatozoa
      in real time at high magnification and has allowed the introduction of a modified
      microinjection procedure, intracytoplasmic morphologically selected sperm
      injection (IMSI). Since its development, several studies have intensively
      investigated the efficacy of MSOME and IMSI. The objective of the present study
      is to review the current literature on the MSOME and IMSI techniques. 

PMID- 23948450
TI  - The impact of sperm DNA damage in assisted conception and beyond: recent advances
      in diagnosis and treatment.
AB  - Sperm DNA damage is a useful biomarker for male infertility diagnosis and
      prediction of assisted reproduction outcomes. It is associated with reduced
      fertilization rates, embryo quality and pregnancy rates, and higher rates of
      spontaneous miscarriage and childhood diseases. This review provides a synopsis
      of the most recent studies from each of the authors, all of whom have major track
      records in the field of sperm DNA damage in the clinical setting. It explores
      current laboratory tests and the accumulating body of knowledge concerning the
      relationship between sperm DNA damage and clinical outcomes. The paper proceeds
      to discuss the strengths, weaknesses and clinical applicability of current sperm
      DNA tests. Next, the biological significance of DNA damage in the male germ line
      is considered. Finally, as sperm DNA damage is often the result of oxidative
      stress in the male reproductive tract, the potential contribution of antioxidant
      therapy in the clinical management of this condition is discussed. DNA damage in
      human spermatozoa is an important attribute of semen quality. It should be part
      of the clinical work up and properly controlled trials addressing the
      effectiveness of antioxidant therapy should be undertaken as a matter of urgency.
      Sperm DNA damage is a useful biomarker for male infertility diagnosis and
      prediction of assisted reproduction outcomes. It is associated with reduced
      fertilization rates, embryo quality and pregnancy rates, and higher rates of
      spontaneous miscarriage and childhood diseases. With all of these fertility check
      points, it shows more promise than conventional semen parameters from a
      diagnostic perspective. Despite this, few infertility clinics use it routinely.
      This review provides a synopsis of the most recent studies from each of the
      authors, all of whom have major track records in the field of sperm DNA damage in
      the clinical setting. It explores current laboratory tests and the accumulating
      body of knowledge concerning the relationship between sperm DNA damage and
      clinical outcomes. The paper proceeds to discuss the strengths and weaknesses and
      clinical applicability of current sperm DNA fragmentation tests. Next, the
      biological significance of DNA damage in the male germ line is considered.
      Finally, as sperm DNA damage is often the result of increased oxidative stress in
      the male reproductive tract, the potential contribution of antioxidant therapy in
      the clinical management of this condition is discussed. As those working in this
      field of clinical research, we conclude that DNA damage in human spermatozoa is
      an important attribute of semen quality which should be carefully assessed in the
      clinical work up of infertile couples and that properly controlled trials
      addressing the effectiveness of antioxidant therapy should be undertaken as a
      matter of urgency. 

PMID- 23948451
TI  - Uterine plasticity and reproductive fitness.
AB  - Reproduction in humans is unique in two major aspects. First, the incidence of
      chromosomally abnormal and developmentally compromised human preimplantation
      embryos is exceptionally high, and second, the uterus decidualizes spontaneously
      each cycle, a process also responsible for the menstrual shedding of the
      endometrium in the absence of pregnancy. Emerging evidence suggests that these
      distinctive reproductive traits are functionally linked. Thus, the decidual
      process enables the mother to limit investment in compromised pregnancies, while
      menstruation imposes a need for constant recruitment of mesenchymal stem cells to
      regenerate and renew the endometrium each cycle. Endometrial stem cells are
      immune-privileged compared with other types of adult stem cells, suggesting a
      role for these cells in accommodating deeply invading semi-allogenic fetal
      trophoblast. Thus, by coupling reproductive competence to a process of constant
      tissue renewal, decidualization enables the human uterus to adapt to pregnancy
      failure and a changing ecology.

PMID- 23948452
TI  - Age-related normogram for antral follicle count in women with polycystic ovary
      syndrome.
AB  - Antral follicle count (AFC) has been shown to be a reliable marker for ovarian
      reserve. The aims of this study were to create an age-related normogram for AFC
      in infertile women with polycystic ovary syndrome (PCOS) and to compare age
      related decline in AFC between infertile women with and without PCOS. A
      retrospective cohort study was conducted. Of a total of 4956 women, 619 women fit
      criteria for PCOS. In those with PCOS, there were large variations in the AFC
      between the 10th and 90th percentiles in all age groups. The rate of decline in
      AFC among women with PCOS was linear, while in those with non-PCOS, it was
      exponential until 30 years of age, and then became similar to that of PCOS. The
      rate of follicle loss per year was significantly slower in PCOS women compared
      with that in non-PCOS women. In both groups, the fastest period of follicle loss
      was between the ages of 18 and 30. The average follicle loss was 0.8
      follicles/year in PCOS women and 1.7 follicles/year in those without PCOS
      (P<0.001). This study concludes that age-related decline in AFC among women with
      PCOS is slower than in those without PCOS. Antral follicle count (AFC) has been
      shown to be a reliable marker for ovarian reserve. The aims of this study were to
      create an age-related normogram for AFC in women with polycystic ovary syndrome
      (PCOS), and to compare age-related decline in AFC between women with and without
      PCOS. A retrospective cohort study was conducted. All patients underwent a
      baseline transvaginal ultrasound that was performed on day 2-4 of the menstrual
      cycle. The total number of antral follicles of 2-9mm in diameter was recorded. Of
      total 4956 women, 619 women fit criteria for PCOS. In those with PCOS, there were
      large variations in the AFC between the 10th 90th percentiles in all age groups.
      The rate of decline in AFC among women with PCOS was linear; while in those with
      non-PCOS, it was exponential until 30 years of age, and then became similar to
      that of PCOS. The rate of follicle loss per year was significantly slower in PCOS
      women compared with that in non-PCOS women. In both groups, the fastest period of
      follicle loss was between the ages 18-30 years. The average follicle loss was 0.8
      follicles/year in PCOS women and 1.7 follicles/year in those without PCOS
      (P<0.001). We have concluded that age-related decline in AFC among women with
      PCOS is slower than in those without PCOS. Further studies are needed to
      determine if the AFC normogram in women with PCOS could be clinically relevant to
      select the optimal gonadotrophin dose for ovulation induction. 

PMID- 23948453
TI  - Ozone-induced oxidative modification of plasma fibrin-stabilizing factor.
AB  - The plasma fibrin-stabilizing factor (pFXIII) function is to maintain a
      hemostasis by the fibrin clot stabilization. The conversion of pFXIII to the
      active form of the enzyme (FXIIIa) is a multistage process. Ozone-induced
      oxidation of pFXIII has been investigated at different stages of its enzyme
      activation. The biochemical results point to a decrease of an enzymatic activity
      of FXIIIa depending largely on the stage of the pFXIII conversion into FXIIIa at
      which oxidation was carried out. UV-, FTIR- and Raman spectroscopy demonstrated
      that chemical transformation of cyclic, NH, SH and S-S groups mainly determines
      the oxidation of amino acid residues of pFXIII polypeptide chains. Conversion of
      pFXIII to FXIIIa proved to increase protein sensitivity to oxidation in the
      order: pFXIII<pFXIII activated by thrombin<pFXIII in the presence of calcium
      ions<FXIIIa. The dynamic light scattering data indicate that the three
      dimensional structure of pFXIII becomes loosened due to oxidative modification.
      ESR spectroscopy data also point to conformational changes of the fibrin
      stabilizing factor under oxidation. Taking into account these new findings it
      seems reasonable to assume that the inhibitory/carrier FXIII-B subunits can serve
      as scavengers of ROS. Hypothetically, this mechanism could help to protect the
      key amino acid residues of the FXIII-A subunits responsible for the enzymatic
      function of FXIIIa. 

PMID- 23948454
TI  - Size discrepancy between sonographic and pathological evaluation of solitary
      papillary thyroid carcinoma.
AB  - BACKGROUND: Sonographic size of suspicious thyroid lesions is an essential
      parameter in the evaluation of thyroid nodules, determining the need for needle
      biopsy and has impact on the extent of surgery. Limited data is available on the
      correlation between the size of the thyroid nodule on sonography and the actual
      size measured during histological examination. The aim of the present study was
      to compare these two modalities and to discuss the potential clinical
      implications of the findings in the study population. METHODS: The database of
      Rabin Medical Center was reviewed for all patients with histologically proven
      papillary carcinoma of the thyroid treated by thyroid surgery between 2005 and
      2010. RESULTS: 292 patients with papillary thyroid carcinoma were included. The
      mean sonographic size of the nodule was 2.19 +/- 1.15 cm. The mean pathological
      diameter was 1.69 +/- 1.09 cm. Discrepancies between tumor histological diameter
      and the sonographically measurement were more prominent in tumors larger than 1.5
      cm. Nonetheless, 18.8% of thyroid nodules that were measured by US as larger than
      1cm, were found to be smaller than 1cm on final pathology. Similarly, 7.2% of
      nodules evaluated by sonography were determined as being larger than 4 cm, while
      their definitive size was smaller than 4 cm. CONCLUSIONS: We noted a significant
      discrepancy between the preoperative sonographic and the pathologic size
      measurements for papillary thyroid carcinoma. The sonographic evaluation
      misclassifies both patients with small and large thyroid tumors, and consequently
      exposes them to unnecessary workup and more extensive operation. This discrepancy
      between the ultrasound findings and actual tumor size should be taken into
      account in clinical practice and help guide the evaluation and treatment of
      patients with thyroid nodules.

PMID- 23948455
TI  - Synthesis and properties of novel ester-containing gemini imidazolium
      surfactants.
AB  - Novel ester-containing gemini imidazolium surfactants were synthesized from
      various aliphatic acids (C12, C14, C16), 1-methylimidazol, and 2,2-bis
      (bromomethyl)-1,3-propanediol with a two step reaction. The surfactants are
      abbreviated as [Cnim]2 (n=12, 14, 16). The chemical structures of the prepared
      compounds were confirmed by (1)H NMR, IR spectra, and elemental analysis. Thermal
      properties of these new surfactants were studied with thermogravimetry (TG) and
      differential scanning calorimetry (DSC). Their critical micelle concentrations
      (cmc) in the aqueous solutions were determined by surface tension and electrical
      conductivity methods. Surface tension parameters including Gammacmc, Amin, and
      gammacmc were obtained. The parameters beta (degree of counterion binding to
      micelles), DeltaGads(0) (Gibbs free energy of adsorption), and DeltaGmic(0)
      (Gibbs free energy change of micellization) were also derived. The results
      indicated that these novel gemini surfactants exhibited very low cmcs and a good
      efficiency in lowering the surface tension of water. Dynamic light scattering
      (DLS) measurements showed that [C12im]2 and [C14im]2 can easily form vesicles at
      very low concentration, and that the self-assembly of [C14im]2 is more well
      organized than for [C12im]2. The use of DOSY and DLS as a complementary technique
      shows that a dynamic micelle-vesicle equilibrium exists in solution. 

PMID- 23948456
TI  - Influence of metakaolin purities on potassium geopolymer formulation: The
      existence of several networks.
AB  - Geopolymer materials are obtained by the alkaline activation of aluminosilicate
      sources, the best of which is metakaolin. However, every raw material is
      different, and very few comparative studies have been done on different
      metakaolin sources. The aim of this work is to develop methods for the prediction
      of the working properties of geopolymer materials based on the reactivity of the
      metakaolin employed. Infrared spectroscopy showed direct relationships between
      the wettability, the Si/Al ratio and the kinetics of conversion of Si-O-Si bonds
      to Si-O-Al bonds. Moreover, it was demonstrated that the presence of impurities
      and the reactivity of the metakaolin can generate the formation of one or several
      networks. Finally, a descriptive model of the mechanism of geopolymer formation
      was proposed that takes into account the quality of metakaolin used. 

PMID- 23948457
TI  - EDTA functionalized silica for removal of Cu(II), Zn(II) and Ni(II) from aqueous
      solution.
AB  - Ethylenediaminetetraacetic acid (EDTA) functionalized silica adsorbent has been
      synthesized using (3-aminopropyl) triethoxylsilane (APTES) as a bridging link
      between silanol groups (SiOH) of silica and carboxylic group of EDTA. Fourier
      transform infrared spectroscopy (FTIR) and Temperature-programmed oxidation (TPO)
      analysis confirmed the grafting of EDTA onto the silica. The synthesized EDTA
      silica was investigated as an adsorbent for removal of Cu(II), Zn(II) and Ni(II)
      from aqueous solution. The effect of solution pH, initial solution concentration,
      and contact time were studied. The removal of metal ions increased with the
      increase in solution pH, contact time and concentration. The maximum equilibrium
      time was found to be 45min for all three metal ions. Kinetics studies revealed
      that the adsorption of Cu(II), Zn(II) and Ni(II) onto EDTA-silica followed the
      pseudo-second order kinetics and film diffusion and intra-particle diffusion
      mechanism were involved. Adsorption equilibrium data were well fitted to Langmuir
      isotherm model and maximum monolayer adsorption capacity for Cu(II), Zn(II) and
      Ni(II) was 79.36, 74.07 and 67.56mg g(-1), respectively. Thermodynamic results
      reveal that the removal of metals onto EDTA-silica was endothermic and
      spontaneous in nature.

PMID- 23948458
TI  - Interaction of a trehalose lipid biosurfactant produced by Rhodococcus
      erythropolis 51T7 with a secretory phospholipase A2.
AB  - Trehalose-containing glycolipid biosurfactants form an emerging group of
      interesting compounds, which alter the structure and properties of phospholipid
      membranes, and interact with enzymatic and non-enzymatic proteins. Phospholipases
      A2 constitute a class of enzymes that hydrolyze the sn-2 ester of
      glycerophospholipids, and are classified into secreted phospholipases A2 (sPLA2)
      and intracellular phospholipases A2. In this work, pancreatic sPLA2 was chosen as
      a model enzyme to study the effect of the trehalose lipid biosurfactant on
      enzymes acting on interfaces. By using this enzyme, it is possible to study the
      modulation of enzyme activity, either by direct interaction of the biosurfactant
      with the protein, or as a result of the incorporation of the glycolipid on the
      phospholipid target membrane. It is shown that the succinoyl trehalose lipid
      isolated from Rhodococcus erythropolis 51T7 interacts with porcine pancreatic
      sPLA2 and inhibits its catalytic activity. Two modes of inhibition are observed,
      which are clearly differentiated by its timescale. First, a slow inhibition of
      sPLA2 activity upon preincubation of the enzyme with trehalose lipid in the
      absence of substrate is described. Second, incorporation of trehalose lipid into
      the phospholipid target membrane gives rise to a fast enzyme inhibition. These
      results are discussed in the light of previous data on sPLA2 inhibitors and
      extend the list of interesting biological activities reported for this R.
      erythropolis trehalose lipid biosurfactant. 

PMID- 23948459
TI  - Hydrothermal formation of N-doped (BiO)2CO3 honeycomb-like microspheres
      photocatalysts with bismuth citrate and dicyandiamide as precursors.
AB  - In order to develop efficient visible light driven photocatalysts for
      environmental application, novel N-doped (BiO)2CO3 honeycomb-like hierarchical
      microspheres were fabricated by an one-pot and template-free hydrothermal method,
      firstly using bismuth citrate and dicyandiamide as precursors. The as-prepared
      samples were characterized by XRD, SEM, FT-IR, PL, XPS, and UV-vis DRS in detail.
      The results indicated that the crystal structure and morphology of the samples
      can be tuned by hydrothermal reaction temperature. The source of nitrogen doping
      was from dicyandiamide, which also played a key role in hydrolyzing bismuth
      citrate to produce bismuth ions and citrate ions. The ammonium ions from the
      decomposition of dicyandiamide reacted with bismuth ions and carbonate ions from
      decomposition of citrate ions, producing in situ N-doped (BiO)2CO3 microspheres.
      The doped nitrogen substituted for oxygen in (BiO)2CO3 and was responsible for
      the band gap reduction of N-doped (BiO)2CO3. The as-prepared N-doped (BiO)2CO3
      microspheres were applied for removal of NO in air and exhibited excellent
      visible light activity, exceeding that of N-doped TiO2 and C-doped TiO2. Time
      dependent evolutions of crystal structure, morphology, chemical composition, and
      optical property were investigated systematically to reveal the growth mechanism
      of the honeycomb-like (BiO)2CO3 microspheres. The growth process involved
      multiple steps, including reaction, nucleation, crystallization, aggregation, and
      recrystallization. The proposed growth mechanism could provide new insights into
      the design and fabrication of hierarchical materials with advanced properties. 

PMID- 23948461
TI  - Adsorption behavior of 6-Mercaptonicotinic acid on self-assembled gold nano
      substrates explored by SERS combined with theoretical calculations.
AB  - As a typical Raman reporter molecule, 6-Mercaptonicotinic acid (C6H5NO2S, MNA)
      has three atoms (i.e., N, O, and S), which could be potential to chemically
      interact with gold nano-surface. In the present report, the adsorption behavior
      of MNA on self-assembled gold nano-substrates is explored by means of surface
      enhanced Raman scattering and theoretical calculations. The results reveal that
      all the enhanced bands are assigned to in-plane vibrations. The ring triangle
      breathing coupling with CS stretching band at 1108cm(-)(1) is enhanced a lot and
      redshifts to 1088cm(-)(1) in the SERS spectra. Furthermore, most of the bands
      related to N atom are apparently enhanced and shift in the SERS spectra. Based on
      the surface selection rule, it infers that MNA is vertically chemisorbed on self
      assembled gold substrates through the S and the N atoms. The spectroscopic
      results are further interpreted by the density functional theory (DFT)
      calculations. 

PMID- 23948460
TI  - Synthesis and neuro-cytocompatibility of magnetic Zn-ferrite nanorods via peptide
      assisted process.
AB  - In order to obtain magnetic nanorods (MNRs) with the neuro-cytocompatibility,
      silk-fibroin (SF)-coated Zn-ferrite NRs are successfully prepared via a
      mineralization process, and their saturation magnetization is 32emu g(-)(1).
      After the mineralization of 2d and 4d in the mixed solution of the concentrations
      of 15w/w% SF and 0.01M HCl, the lengths of NRs are ~220nm and ~2MUm,
      respectively. Cell tests of NRs with 220nm length showed that the as-prepared Zn
      ferrite NRs hardly produced toxicity on Escherichiacoli, Staphylococcusaureus,
      L929, and PC12 cells. The results of the outgrown neurites from PC12 cells
      indicated that the neurite length and the number of neurites were not
      significantly decreased at the low concentrations of SF-coated NRs (less than
      0.25mg mL(-)(1)) in 1-5d culture time. TEM images of cell ultrathin sections
      indicated that, although Zn-ferrite NRs were split in the cytosol for 5d at the
      NR concentrations of 0.125mg mL(-)(1), some integrated mitochondria in a neurite
      suggested that SF-coated NRs inside cells did not influence the extension
      activity of neurites. Based on the good neuro-cytocompatibility and magnetic
      property of Zn-ferrite NRs, their potential applications in safe cell
      manipulation and axon guidance can be envisioned.

PMID- 23948462
TI  - The efficacy of induction chemotherapy with docetaxel, cisplatin and 5
      fluorouracil combined with cisplatin concurrent chemoradiotherapy for locally
      advanced head and neck squamous cell carcinoma: a matched pair analysis.
AB  - AIMS: The role of induction chemotherapy (ICT) for head and neck squamous cell
      carcinoma (HNSCC) is controversial. The aim of the study was to assess the
      benefit of ICT with docetaxel, cisplatin and 5-fluorouracil (5-FU) (TPF) when
      combined with concurrent cisplatin chemoradiotherapy (CRT) for HNSCC. MATERIALS
      AND METHODS: Patients with HNSCC treated between January 2005 and December 2010
      with radical intent with either TPF or cisplatin and 5-FU (PF) ICT and documented
      intention to proceed with concurrent cisplatin CRT were identified
      retrospectively. The use and choice of ICT regimen was at the clinician's
      discretion. In total, 68 patients treated with TPF were identified and were
      matched for T and N stage and tumour site to 68 patients treated with PF. A
      survival analysis was carried out using Kaplan-Meier and the Cox proportional
      hazards model. RESULTS: The median follow-up was 29.9 versus 36.3 months for the
      TPF and PF groups, respectively. Three year locoregional relapse-free survival
      (RFS), distant RFS, RFS, cancer-specific survival and overall survival rates for
      the TPF and PF groups were 84.2, 91.6, 82.6, 81.3 and 74.9% versus 73.7, 84.9,
      71.9, 72.1 and 62.9%, respectively. On multivariate analysis, treatment with TPF
      predicted for improved locoregional RFS (P = 0.03) and overall survival (P =
      0.05). CONCLUSION: The addition of docetaxel to a cisplatin doublet ICT regimen
      before concurrent CRT may improve disease control for locally advanced HNSCC.

PMID- 23948463
TI  - Association between perifoveal hyperfluorescence and serous retinal detachment in
      diabetic macular edema.
AB  - OBJECTIVE: To study the association between the fluorescence levels on
      fluorescein angiography images and the characteristics on spectral-domain optical
      coherence tomography (SD OCT) images in diabetic macular edema (DME). DESIGN:
      Retrospective, observational, cross-sectional study. PARTICIPANTS: One hundred
      sixty-seven consecutive eyes of 116 patients with diabetic retinopathy for whom
      FA and SD OCT were performed on the same day. METHODS: Fluorescein angiography
      using the Heidelberg Retina Angiograph 2 and OCT images using Spectralis OCT
      (Heidelberg Engineering, Heidelberg, Germany) were obtained. The leakage of
      fluorescein dye in each subfield of the Early Treatment Diabetic Retinopathy
      Study (ETDRS) grid was quantified and defined as fluorescence levels, which were
      compared with the retinal thickness and foveal pathomorphologic features
      evaluated by SD OCT. MAIN OUTCOME MEASURES: The relationship between fluorescence
      levels and the foveal pathomorphologic features on SD OCT images. RESULTS: One
      hundred twelve (67%) eyes with center-involved DME had significantly higher
      fluorescence levels in all subfields of the ETDRS grid than 55 (33%) eyes without
      DME. Fluorescence levels were correlated modestly with the retinal thickness in
      individual subfields in eyes with center-involved DME. Thirty-seven eyes with
      foveal serous retinal detachment (SRD) had greater retinal thickness in all
      subfields and higher levels of fluorescence in most subfields, except the
      superior subfield of the inner ring. After adjusting for the central retinal
      thickness using multivariate analyses, eyes with SRD had significantly (P =
      0.0085) higher fluorescence levels in the nasal subfield of the inner ring and
      the superior, nasal, and inferior subfields of the outer ring (P = 0.0117, P =
      0.0020, and P = 0.0017, respectively). However, the fluorescence levels in any
      subfields of the inner or outer ring did not differ significantly between eyes
      with and without foveal cystoid spaces. CONCLUSIONS: The correlation between the
      fluorescence levels and retinal thickness suggests that the vascular
      hyperpermeability in the perifovea contributes to the pathogenesis of foveal SRD
      in DME.

PMID- 23948464
TI  - Demographic and clinical profile of ocular chemical injuries in the pediatric age
      group.
AB  - OBJECTIVE: To review the risk factors, management, and visual outcomes of
      pediatric chemical eye injuries in a tertiary care hospital in North India.
      DESIGN: Retrospective hospital-based study. PARTICIPANTS: Patients aged <16 years
      with ocular chemical burns. METHODS: Case records of patients with ocular
      chemical injury who presented to the Dr. Rajendra Prasad Centre for Ophthalmic
      Sciences were reviewed over a 5-year period. MAIN OUTCOME MEASURES: Demographic
      profile, nature of chemical injury, complications, and visual outcomes after
      chemical injury. RESULTS: A total of 134 pediatric patients with a history of
      ocular chemical burns were seen between March 2006 and March 2011. The mean age
      of patients at the time of injury was 8.95+/-4.89 years (range, 1.2-15.5 years);
      63.4% were male. Sixty-nine patients (51.4%) belonged to the preschool (0-5
      years) age group. Bilateral chemical injuries were seen in 24 patients (17.9%).
      Lime ("chuna") was the most commonly involved chemical (88, 65.6%) followed by
      toilet cleaner (20, 14.9%). The mean time between injury and presentation was
      68.3 days (range, 1-365 days). Severe (grade 3 and 4) ocular chemical injury was
      seen in 94 patients (70.1%). Surgical intervention was performed in 114 eyes
      (85%) in the form of amniotic membrane grafting (n = 78), symblepharon release (n
      = 56), limbal stem cell transplantation (n = 26), and lamellar keratoplasty (n =
      14). The average number of surgeries conducted per patient was 2.3 (range, 1-4).
      Median visual acuity at final follow-up (mean, 537+/-354 days) was 3/60.
      CONCLUSIONS: Chemical injuries in pediatric patients are more commonly
      encountered in the preschool age group and are associated with severe visual
      loss. Alkali injury from bursting of chuna packets was the most common mode of
      injury in pediatric patients in our study.

PMID- 23948465
TI  - Evaluation of progressive neuroretinal rim loss as a surrogate end point for
      development of visual field loss in glaucoma.
AB  - PURPOSE: To evaluate the validity of using progressive loss of neuroretinal rim
      area as a surrogate end point for the development of visual field loss in
      glaucoma. DESIGN: Prospective, observational cohort study. PARTICIPANTS: The
      study group included 492 eyes of 328 patients classified with suspected glaucoma
      at the baseline visit. These eyes had an average of 7.4+/-2.8 confocal scanning
      laser ophthalmoscopy (CSLO) images during a mean follow-up time of 6.6+/-1.6
      years. METHODS: Rim area measurements were acquired with CSLO during follow-up.
      The visual field end point was considered the development of 3 consecutive
      abnormal visual fields on standard automated perimetry. Strong predictive ability
      and large proportion of treatment effect (PTE) explained are requisites for a
      suitable surrogate end point. A joint longitudinal survival model was used to
      evaluate the ability of rates of rim area loss in predicting visual field
      development, adjusting for confounding variables (baseline age, race, and corneal
      thickness and follow-up measurements of intraocular pressure [IOP] and pattern
      standard deviation). The PTE was calculated by comparing the effect of IOP on the
      risk of development of visual field loss when incorporating rim area loss in the
      same model with the effect of IOP in the model excluding rim area measurements.
      MAIN OUTCOME MEASURES: Predictive strength was measured by survival-adapted R(2)
      and PTE. RESULTS: Sixty-two of 492 eyes (13%) developed visual field loss during
      follow-up. The mean rate of rim area change in eyes that developed visual field
      loss was -0.011 mm(2)/year versus -0.003 mm(2)/year in eyes that did not
      (P<0.001). In the multivariable model, each 0.01 mm(2)/year faster rate of rim
      area loss was associated with a 2.94 higher risk of visual field loss (hazard
      ratio, 2.94; 95% confidence interval, 1.38-6.23; P = 0.005). R(2) values were 62%
      and 81% for univariable and multivariable models, respectively. The PTE was 65%.
      CONCLUSIONS: Progressive rim area loss was highly predictive of the development
      of visual field loss in glaucoma and explained a significant PTE on the
      clinically relevant outcome. These findings suggest that rim area measurements
      may be suitable surrogate end points in glaucoma clinical trials.

PMID- 23948466
TI  - Three-dimensional evaluation of accommodating intraocular lens shift and
      alignment in vivo.
AB  - OBJECTIVE: To quantify 3-dimensionally the anterior segment geometry, biometry,
      and lens position and alignment in patients before and after implantation of the
      Crystalens-AO (Bausch & Lomb, Rochester, NY) accommodating intraocular lens (A
      IOL). DESIGN: Prospective, observational study. PARTICIPANTS: Ten patients (20
      eyes) with cataract before and after implantation of the Crystalens-AO A-IOL.
      METHODS: Custom full anterior segment 3-dimensional (3-D) spectral optical
      coherence tomography (OCT) provided with quantification tools was used to image
      the cornea, iris, and natural lens preoperatively and intraocular lens
      postoperatively. Measurements were obtained under phenylephrine preoperatively
      and under natural viewing conditions and phenylephrine (for accommodative efforts
      ranging from 0 to 2.5 diopters [D]) and pilocarpine postoperatively. MAIN OUTCOME
      MEASURES: Three-dimensional quantitative anterior segment images, corneal
      geometry and power, anterior chamber depth (ACD), lens thickness, pupil diameter,
      A-IOL shift with accommodative effort or drug-induced accommodation, and A-IOL
      alignment. RESULTS: Crystalline lens and IOLs were visualized and quantified 3
      dimensionally. The average ACD were 2.64+/-0.24 and 3.65+/-0.35 mm preoperatively
      and postoperatively (relaxed state), respectively, and they were statistically
      significantly correlated (although their difference was not statistically
      correlated with lens thickness). The A-IOL did not shift systematically with
      accommodative effort, with 9 lenses moving forward and 11 lenses moving backward
      (under natural conditions). The average A-IOL shift under stimulated
      accommodation with pilocarpine was -0.02+/-0.20 mm. The greatest forward shift
      occurred bilaterally in 1 patient (-0.49 mm in the right eye and -0.52 mm in the
      left eye, under pilocarpine). The high right/left symmetry in the horizontal tilt
      of the crystalline lens is disrupted on IOL implantation. Accommodative IOLs tend
      to be slightly more vertically tilted than the crystalline lens, with increasing
      tendency with accommodative effort. Two subjects showed postoperative IOL tilts
      >9 degrees. Changes in pupillary diameter correlated with pilocarpine-induced A
      IOL axial shift. Intermediate accommodative demands (1.25 D) elicited the greater
      shifts in axial A-IOL location and tilt and pupil diameter. CONCLUSIONS:
      Quantitative 3-D anterior segment OCT allows full evaluation of the geometry of
      eyes implanted with A-IOLs preoperatively and postoperatively. High-resolution
      OCT measurements of the Crystalens 3-D positioning revealed small (and in many
      patients backward) A-IOL axial shifts with both natural or drug-induced
      accommodation, as well as tilt changes with respect to natural lens and
      accommodative effort.

PMID- 23948467
TI  - Development of protective anti-Mycoplasma pneumoniae antibodies after
      immunization of guinea pigs with the combination of a P1-P30 chimeric recombinant
      protein and chitosan.
AB  - The attachment organelle of the human respiratory tract pathogen Mycoplasma
      pneumoniae is essential for colonization of the host mucosa. Furthermore,
      adherence-related proteins such as the major adhesin P1 and protein P30 represent
      vaccine candidates. Using the chimeric recombinant protein HP14/30, which
      combines surface-localized and adherence-involved regions of both proteins, we
      developed an optimized strategy to immunize guinea pigs. The vaccination protocol
      includes subcutaneous prime immunization followed by presentation of the antigen
      directly to the respiratory mucosa by two intranasal (i.n.) administrations and
      combination of antigen with the mucosal adjuvant chitosan. The immunization
      scheme induced high, consistent and long-lasting IgA levels in respiratory tract
      samples (BAL, nasal and throat washing fluid) from the animals. In comparison
      with a preimmune serum, incubation of M. pneumoniae cells with sera from these
      animals reduced the mean adhesion of bacteria to HeLa cells to 6%. After i.n.
      infection, immunized animals showed significantly decreased numbers of M.
      pneumoniae-specific genome copies, especially in the upper respiratory tract, in
      comparison with the control group. The results demonstrated that optimized
      immunization with the chimeric protein HP14/30 is promising for further
      vaccination efforts to prevent host colonization with M. pneumoniae. 

PMID- 23948468
TI  - BDSF inhibits Candida albicans adherence to urinary catheters.
AB  - Cis-2-dodecenoic acid (BDSF) is a quorum-sensing signal molecule produced by the
      opportunistic pathogen Burkholderia cenocepacia and suppresses germ tube
      formation of Candida albicans. An in vitro model for biofilm formation evaluated
      the influence of BDSF on C. albicans. Biofilm morphology was observed using
      scanning electron microscopy, cell adherence was determined using polystyrene
      plates and siliconized urinary catheters, and the levels of expression of genes
      involved in adhesion were determined using Real-time Reverse-Transcriptase
      Polymerase Chain Reaction. BDSF inhibited initial biofilm formation by a clinical
      isolate of C. albicans and reduced its capability to adhere to the polystyrene
      surface. BDSF at concentrations up to 120 MUM did not significantly affect the
      viability of C. albicans. BDSF (90 MUM) inhibited cell adherence to plates and
      catheters by 4- and 25-fold. Compared with untreated yeasts, the level of
      expression of genes involved in adhesion, ALS1 and EAP1, were reduced by 4- and
      0.25-fold, whereas that of YWP1 was increased at a 4-fold higher level. Here we
      show that BDSF effectively inhibited biofilm development as indicated by its
      ability to inhibit adherence. Thus, BDSF should be considered as a potential
      therapeutic agent to prevent disease caused by Candida species. 

PMID- 23948469
TI  - Mate preference in the painted goby: the influence of visual and acoustic
      courtship signals.
AB  - We tested the hypothesis that females of a small vocal marine fish with exclusive
      paternal care, the painted goby, prefer high parental-quality mates such as large
      or high-condition males. We tested the effect of male body size and male visual
      and acoustic courtship behaviour (playback experiments) on female mating
      preferences by measuring time spent near one of a two-choice stimuli. Females did
      not show preference for male size but preferred males that showed higher levels
      of courtship, a trait known to advertise condition (fat reserves). Also, time
      spent near the preferred male depended on male courtship effort. Playback
      experiments showed that when sound was combined with visual stimuli (a male
      confined in a small aquarium placed near each speaker), females spent more time
      near the male associated with courtship sound than with the control male
      (associated with white noise or silence). Although male visual courtship effort
      also affected female preference in the pre-playback period, this effect decreased
      during playback and disappeared in the post-playback period. Courtship sound
      stimuli alone did not elicit female preference in relation to a control. Taken
      together, the results suggest that visual and mainly acoustic courtship displays
      are subject to mate preference and may advertise parental quality in this
      species. Our results indicate that visual and acoustic signals interplay in a
      complex fashion and highlight the need to examine how different sensory
      modalities affect mating preferences in fish and other vertebrates. 

PMID- 23948470
TI  - Thermal dependence of cardiac function in arctic fish: implications of a warming
      world.
AB  - With the Arctic experiencing one of the greatest and most rapid increases in sea
      temperatures in modern time, predicting how Arctic marine organisms will respond
      to elevated temperatures has become crucial for conservation biology. Here, we
      examined the thermal sensitivity of cardiorespiratory performance for three
      closely related species of sculpins that inhabit the Arctic waters, two of which,
      Gymnocanthus tricuspis and Myoxocephalus scorpioides, have adapted to a
      restricted range within the Arctic, whereas the third species, Myoxocephalus
      scorpius, has a wider distribution. We tested the hypothesis that the fish
      restricted to Arctic cold waters would show reduced cardiorespiratory scope in
      response to an increase in temperature, as compared with the more eurythermal M.
      scorpius. As expected from their biogeography, M. scorpioides and G. tricuspis
      maximised cardiorespiratory performance at temperatures between 1 and 4 degrees
      C, whereas M. scorpius maximised performance over a wider range of temperatures
      (1-10 degrees C). Furthermore, factorial scope for cardiac output collapsed at
      elevated temperature for the two high-latitude species, negatively impacting
      their ability to support aerobically driven metabolic processes. Consequently,
      these results concurred with our hypothesis, suggesting that the sculpin species
      restricted to the Arctic are likely to be negatively impacted by increases in
      ocean temperatures. 

PMID- 23948471
TI  - Visual contrast and color in rapid learning of novel patterns by chicks.
AB  - Biological communication signals often combine bright and dark colors, such as
      yellow and black, but it is unclear why such patterns are effective. The
      literature on aposematism suggests that high contrast patterns may be easily
      learnt or innately avoided, whereas studies of sexual signaling refer to their
      attractiveness or to their cost. Here, in experiments with poultry chicks trained
      to find food in patterned containers, we confirm that elevated contrast
      dramatically increases the rate of initial attack on novel stimuli, but this
      response is labile. The chicks pecked once at a novel unrewarded stimulus and
      then ignored it for at least 24 h. Such single trial learning has not previously
      been reported for birds without a positively aversive unconditioned stimulus such
      as quinine. We then tested and rejected two hypotheses about the function of high
      contrast patterns: first that the preferential responses are due to novelty, and
      second that elevated contrast enhances learning about a novel color. More
      generally, the observations are consistent with the idea that elevated contrast
      attracts attention, thereby enhancing both initial responses - whether positive
      or negative - and the rate of learning. 

PMID- 23948472
TI  - Cryptic impacts of temperature variability on amphibian immune function.
AB  - Ectothermic species living in temperate regions can experience rapid and
      potentially stressful changes in body temperature driven by abrupt weather
      changes. Yet, among amphibians, the physiological impacts of short-term
      temperature variation are largely unknown. Using an ex situ population of
      Cryptobranchus alleganiensis, an aquatic North American salamander, we tested the
      hypothesis that naturally occurring periods of temperature variation negatively
      impact amphibian health, either through direct effects on immune function or by
      increasing physiological stress. We exposed captive salamanders to repeated
      cycles of temperature fluctuations recorded in the population's natal stream and
      evaluated behavioral and physiological responses, including plasma complement
      activity (i.e. bacteria killing) against Pseudomonas aeruginosa, Escherichia coli
      and Aeromonas hydrophila. The best-fit model (DeltaAICc=0, wi=0.9992) revealed
      70% greater P. aeruginosa killing after exposure to variable temperatures and no
      evidence of thermal acclimation. The same model predicted 50% increased E. coli
      killing, but had weaker support (DeltaAICc=1.8, wi=0.2882). In contrast, plasma
      defenses were ineffective against A. hydrophila, and other health indicators
      (leukocyte ratios, growth rates and behavioral patterns) were maintained at
      baseline values. Our data suggest that amphibians can tolerate, and even benefit
      from, natural patterns of rapid warming/cooling. Specifically, temperature
      variation can elicit increased activity of the innate immune system. This immune
      response may be adaptive in an unpredictable environment, and is undetectable by
      conventional health indicators (and hence considered cryptic). Our findings
      highlight the need to consider naturalistic patterns of temperature variation
      when predicting species' susceptibility to climate change. 

PMID- 23948473
TI  - RNA interference of glycerol biosynthesis suppresses rapid cold hardening of the
      beet armyworm, Spodoptera exigua.
AB  - The beet armyworm, Spodoptera exigua, is a freeze-susceptible species that
      overwinters in temperate zones without diapause. A rapid cold hardening (RCH) and
      supercooling capacity usually play crucial roles in survival during the
      overwintering period. This study identified a cryoprotectant as a RCH factor of
      S. exigua. Pre-exposure of S. exigua larvae to 4 degrees C significantly
      increased survival at -10 degrees C in all developmental stages from egg to
      adult. RCH was dependent on the duration of the pre-exposure period. RCH also
      significantly enhanced the supercooling capacity. Cryoprotectant analysis using
      HPLC showed that the pre-exposure treatment allowed the larvae to accumulate
      glycerol in the hemolymph. Two genes, glycerol-3-phosphate dehydrogenase (GPDH)
      and glycerol kinase (GK), were identified as being associated with glycerol
      biosynthesis, and were cloned from S. exigua larvae. Both GPDH and GK were
      expressed in all developmental stages of S. exigua. RNA interference (RNAi) of
      either GPDH or GK significantly inhibited glycerol accumulation in the hemolymph
      of S. exigua. Larvae treated with RNAi for GPDH or GK exhibited a significant
      decrease in RCH capacity. The glycerol accumulation in response to 4 degrees C
      appeared to be under the control of a humoral signal, because a ligation
      experiment prevented glycerol accumulation in the other half of the body. This
      study indicates that glycerol is a RCH factor of S. exigua and its synthesis is
      in response to low temperature via humoral mediation. 

PMID- 23948474
TI  - Physiological control of bioluminescence in a deep-sea planktonic worm,
      Tomopteris helgolandica.
AB  - Tomopteris helgolandica Greeff 1879 (Tomopteridae) is a transparent
      holoplanktonic polychaete that can emit a bright light. In this study, we
      investigated the emission pattern and control of this deep-sea worm's
      luminescence. Potassium chloride depolarisation applied on anaesthetised
      specimens triggered a maximal yellow light emission from specific parapodial
      sites, suggesting that a nervous control pathway was involved. Pharmacological
      screening revealed a sensitivity to carbachol, which was confirmed by a dose
      light response associated with a change in the light emission pattern, where
      physiological carbachol concentrations induced flashes and higher concentrations
      induced glows. The light response induced by its hydrolysable agonist,
      acetylcholine, was significantly weaker but was facilitated by eserine
      pretreatment. In addition, a specific inhibitory effect of tubocurarine was
      observed on carbachol-induced emission. Lastly, KCl- and carbachol-induced light
      responses were significantly reduced when preparations were pre-incubated in
      Ca(2+)-free artificial seawater or in different calcium channel blockers
      (verapamil, diltiazem) and calmodulin inhibitor (trifluoperazine) solutions. All
      of these results strongly suggest that T. helgolandica produces its light flashes
      via activation of nicotinic cholinergic receptors and a calcium-dependent
      intracellular mechanism involving L-type calcium channels. 

PMID- 23948475
TI  - Frog nuptial pads secrete mating season-specific proteins related to salamander
      pheromones.
AB  - Males of many frog species develop spiny nuptial pads with underlying glands on
      their thumbs during the mating period. We used 3D visualization on the European
      common frog Rana temporaria to show that the morphology of these glands allows
      the channelling of secreted molecules to the pad's surface during amplexus.
      Combined transcriptome and proteome analyses show that proteins of the Ly-6/uPAR
      family, here termed amplexins, are highly expressed in the nuptial glands during
      the mating season, but are totally absent outside that period. The function of
      amplexins remains unknown, but it is interesting to note that they share
      structural similarities with plethodontid modulating factors, proteins that
      influence courtship duration in salamanders. 

PMID- 23948476
TI  - Immune response to a Trichinella spiralis infection in house mice from lines
      selectively bred for high voluntary wheel running.
AB  - Four lines of mice bred for high voluntary wheel running (HR lines) have high
      baseline circulating corticosterone levels and increased daily energy expenditure
      as compared with four non-selected control (C) lines. High corticosterone may
      suppress immune function and competing energy demands may limit ability to mount
      an immune response. We hypothesized that HR mice have a reduced immune response
      and therefore a decreased ability to fight an infection by Trichinella spiralis,
      an ecologically relevant nematode common in mammals. Infections have an acute,
      intestinal phase while the nematode is migrating, reproducing and traveling
      throughout the bloodstream, followed by a chronic phase with larvae encysted in
      muscles. Adult males (generation 55 of the selection experiment) were sham
      infected or infected by oral gavage with ~300 J1 T. spiralis larvae. During the
      chronic phase of infection, mice were given wheel access for 6 days, followed by
      2 days of maximum aerobic performance trials. Two weeks post-infection, infected
      HR had significantly lower circulating immunoglobulin E levels compared with
      infected C mice. However, we found no statistical difference between infected HR
      and C mice in numbers of encysted larvae within the diaphragm. As expected, both
      voluntary running and maximum aerobic performance were significantly higher in HR
      mice and lower in infected mice, with no line type-by-infection interactions.
      Results complement those of previous studies suggesting decreased locomotor
      abilities during the chronic phase of T. spiralis infection. However, despite
      reduced antibody production, breeding for high voluntary wheel exercise does not
      appear to have a substantial negative impact on general humoral function. 

PMID- 23948477
TI  - Neuromuscular control of hovering wingbeat kinematics in response to distinct
      flight challenges in the ruby-throated hummingbird, Archilochus colubris.
AB  - While producing one of the highest sustained mass-specific power outputs of any
      vertebrate, hovering hummingbirds must also precisely modulate the activity of
      their primary flight muscles to vary wingbeat kinematics and modulate lift
      production. Although recent studies have begun to explore how pectoralis (the
      primary downstroke muscle) neuromuscular activation and wingbeat kinematics are
      linked in hummingbirds, it is unclear whether different species modulate these
      features in similar ways, or consistently in response to distinct flight
      challenges. In addition, little is known about how the antagonist, the
      supracoracoideus, is modulated to power the symmetrical hovering upstroke. We
      obtained simultaneous recordings of wingbeat kinematics and electromyograms from
      the pectoralis and supracoracoideus in ruby-throated hummingbirds (Archilochus
      colubris) hovering under the following conditions: (1) ambient air, (2) air
      density reduction trials, (3) submaximal load-lifting trials and (4) maximal load
      lifting trials. Increased power output was achieved through increased stroke
      amplitude during air density reduction and load-lifting trials, but wingbeat
      frequency only increased at low air densities. Overall, relative
      electromyographic (EMG) intensity was the best predictor of stroke amplitude and
      is correlated with angular velocity of the wingtip. The relationship between
      muscle activation intensity and kinematics was independent of treatment type,
      indicating that reduced drag on the wings in hypodense air did not lead to high
      wingtip angular velocities independently of increased muscle work. EMG bursts
      consistently began and ended before muscle shortening under all conditions.
      During all sustained hovering, spike number per burst consistently averaged 1.2
      in the pectoralis and 2.0 in the supracoracoideus. The number of spikes increased
      to 2.5-3 in both muscles during maximal load-lifting trials. Despite the relative
      kinematic symmetry of the hovering downstroke and upstroke, the supracoracoideus
      was activated ~1 ms earlier, EMG bursts were longer (~0.9 ms) and they exhibited
      1.6 times as many spikes per burst. We hypothesize that earlier and more
      sustained activation of the supracoracoideus fibres is necessary to offset the
      greater compliance resulting from the presence of the supracoracoid tendon. 

PMID- 23948478
TI  - Regulatory role of PGC-1alpha/PPAR signaling in skeletal muscle metabolic
      recruitment during cold acclimation.
AB  - This study examined the molecular basis of energy-related regulatory mechanisms
      underlying metabolic recruitment of skeletal muscle during cold acclimation and
      possible involvement of the l-arginine/nitric oxide-producing pathway. Rats
      exposed to cold (4+/-1 degrees C) for periods of 1, 3, 7, 12, 21 and 45 days were
      divided into three groups: untreated, l-arginine treated and N(omega)-nitro-l
      arginine methyl ester (l-NAME) treated. Compared with controls (22+/-1 degrees
      C), there was an initial increase in the protein level of 5'-AMP-activated
      protein kinase alpha (day 1), followed by an increase in peroxisome proliferator
      activated receptor-gamma coactivator-1alpha (PGC-1alpha) and peroxisome
      proliferator-activated receptors (PPARs): PPARalpha and PPARgamma from day 1 and
      PPARdelta from day 7 of cold acclimation. Activation of the PGC-1alpha/PPAR
      transcription program was accompanied by increased protein expression of the key
      metabolic enzymes in beta-oxidation, the tricarboxylic acid cycle and oxidative
      phosphorylation, with the exceptions in complex I (no changes) and ATP synthase
      (decreased at day 1). Cold did not affect hexokinase and GAPDH protein levels,
      but increased lactate dehydrogenase activity compared with controls (1-45 days).
      l-arginine sustained, accelerated and/or intensified cold-induced molecular
      remodeling throughout cold acclimation. l-NAME exerted phase-dependent effects:
      similar to l-arginine in early cold acclimation and opposite after prolonged cold
      exposure (from day 21). It seems that upregulation of the PGC-1alpha/PPAR
      transcription program early during cold acclimation triggers the molecular
      recruitment of skeletal muscle underlying the shift to more oxidative metabolism
      during prolonged cold acclimation. Our results suggest that nitric oxide has a
      role in maintaining the skeletal muscle oxidative phenotype in late cold
      acclimation but question its role early in cold acclimation. 

PMID- 23948479
TI  - Segment-specific and state-dependent targeting accuracy of the stick insect.
AB  - In its natural habitat, Carausius morosus climbs on the branches of bushes and
      trees. Previous work suggested that stick insects perform targeting movements
      with their hindlegs to find support more easily. It has been assumed that the
      animals use position information from the anterior legs to control the touchdown
      position of the ipsilateral posterior legs. Here we addressed the question of
      whether not only the hindleg but also the middle leg performs targeting, and
      whether targeting is still present in a walking animal when influences of
      mechanical coupling through the ground are removed. If this were the case, it
      would emphasize the role of underlying neuronal mechanisms. We studied whether
      targeting occurred in both legs, when the rostral neighboring leg, i.e. either
      the middle or the front leg, was placed at defined positions relative to the
      body, and analyzed targeting precision for dependency on the targeted position.
      Under these conditions, the touchdown positions of the hindlegs show correlation
      to the position of the middle leg parallel and perpendicular to the body axis,
      while only weak correlation exists between the middle and front legs, and only in
      parallel to the body axis. In continuously walking tethered animals, targeting
      accuracy of the hindlegs and middle legs parallel to the body axis barely
      differed. However, targeting became significantly more accurate perpendicular to
      the body axis. Our results suggest that a neural mechanism exists for controlling
      the touchdown position of the posterior leg but that the strength of this
      mechanism is segment specific and dependent on the behavioral context in which it
      is used. 

PMID- 23948480
TI  - Spectral sensitivity of the ctenid spider Cupiennius salei.
AB  - The spectral sensitivity of adult male Cupiennius salei Keys, a nocturnal hunting
      spider, was studied in a behavioural test. As known from earlier behavioural
      tests, C. salei will walk towards a black target presented in front of a white
      background. In this study, a black target (size 42*70 cm) was presented in a
      white arena illuminated by monochromatic light in the range 365-695 nm using 19
      monochromatic filters (half-width in the range 6-10 nm). In the first trial, the
      transmission of the optical filters was between 40% and 80%. In the second trial,
      the transmission was reduced to 5% using a neutral density filter. At the high
      intensity, the spiders showed a spectral sensitivity in the range 380-670 nm. In
      the second trial, the animals only showed directed walks if the illumination was
      in the range 449-599 nm, indicating a lower sensitivity at the margins of the
      spectral sensitivity. In previous intracellular recordings, the measured spectral
      sensitivity was between 320 and 620 nm. Interestingly, these results do not
      completely match the behaviourally tested spectral sensitivity of the
      photoreceptors, where the sensitivity range is shifted to longer wavelengths. In
      order to investigate the molecular background of spectral sensitivity, we
      searched for opsin genes in C. salei. We found three visual opsins that
      correspond to UV and middle to long wavelength sensitive opsins as described for
      jumping spiders. 

PMID- 23948481
TI  - Bumblebee visual search for multiple learned target types.
AB  - Visual search is well studied in human psychology, but we know comparatively
      little about similar capacities in non-human animals. It is sometimes assumed
      that animal visual search is restricted to a single target at a time. In bees,
      for example, this limitation has been evoked to explain flower constancy, the
      tendency of bees to specialise on a single flower type. Few studies, however,
      have investigated bee visual search for multiple target types after extended
      learning and controlling for prior visual experience. We trained colour-naive
      bumblebees (Bombus terrestris) extensively in separate discrimination tasks to
      recognise two rewarding colours in interspersed block training sessions. We then
      tested them with the two colours simultaneously in the presence of distracting
      colours to examine whether and how quickly they were able to switch between the
      target colours. We found that bees switched between visual targets quickly and
      often. The median time taken to switch between targets was shorter than known
      estimates of how long traces last in bees' working memory, suggesting that their
      capacity to recall more than one learned target was not restricted by working
      memory limitations. Following our results, we propose a model of memory and
      learning that integrates our findings with those of previous studies
      investigating flower constancy. 

PMID- 23948482
TI  - Thermoluminescent characterization of HfO2:Tb3+ synthesized by hydrothermal
      route.
AB  - Thermo and photoluminescent properties of nanoparticles (NPs) of hafnium oxide
      (HfO2), both intrinsic and doped with terbium (Tb(3+)) are reported. The NPs of
      HfO2 were synthesized by hydrothermal route, using hafnium tetrachloride (HfCl4)
      and terbium chloride hexahydrated (TbCl3?6H2O) as precursors and sodium hydroxide
      (NaOH) to adjust the pH. Deionized water was used as solvent in all cases. The
      synthesis was carried out at different dopant concentrations from 0 to 20 at% of
      terbium with respect to the amount of hafnium in the precursor solution. The
      temperature of hydrothermal treatment was 200  degrees C and 80 min of reaction
      time. X-ray diffraction results show that at terbium concentrations higher than
      15 at% the HfO2 nanoparticles have a crystalline structure corresponding to the
      tetragonal phase. Thermoluminescent (TL) characterization was performed after 5
      min irradiation of the samples with ultraviolet light of 200 nm wavelength. The
      highest TL emission was observed on samples with 7 at% of Tb, with the TL peak
      centered at 128  degrees C. Thermoluminescence analysis shows behavior associated
      with second-order kinetics with activation energy of 0.49 eV. Photoluminescent
      spectrum present the characteristics (5)D4->(7)FJ (J=3-6) terbium ion electronic
      transitions lines centered on 489 nm, 543 nm, 584 nm and 622 nm.

PMID- 23948483
TI  - Cardiomyocyte-specific ablation of CD36 improves post-ischemic functional
      recovery.
AB  - Although pre-clinical evidence has suggested that partial inhibition of
      myocardial fatty acid oxidation (FAO) and subsequent switch to greater glucose
      oxidation for ATP production can prevent ischemia/reperfusion injury, controversy
      about this approach persists. For example, mice with germline deletion of the FA
      transporter CD36, exhibited either impaired or unchanged post-ischemic functional
      recovery despite a 40-60% reduction in FAO rates. Because there are limitations
      to cardiac studies utilizing whole body CD36 knockout (totalCD36KO) mice, we have
      now generated an inducible and cardiomyocyte-specific CD36 KO (icCD36KO) mouse to
      better address the role of cardiomyocyte CD36 and its regulation of FAO and post
      ischemic functional recovery. Four to six weeks following CD36 ablation, hearts
      from icCD36KO mice had significantly decreased FA uptake compared to controls,
      which was paralleled by significant reductions in intramyocardial triacylglycerol
      content. Analysis of cardiac energy metabolism using ex vivo working heart
      perfusions showed that reduced FAO rates were compensated by enhanced glucose
      oxidation in the hearts from icCD36KO mice. In contrast to the totalCD36KO mice,
      hearts from icCD36KO mice exhibited significantly improved functional recovery
      following ischemia/reperfusion (18min of global no-flow ischemia followed by
      40min of aerobic reperfusion). This improved recovery was associated with lower
      calculated proton production prior to and following ischemia compared to
      controls. Moreover, the amount of ATP generated relative to cardiac work was
      significantly lower in the hearts from icCD36KO mice compared to controls,
      indicating significantly increased cardiac efficiency in the hearts from icCD36KO
      mice. These data provide genetic evidence that reduced FAO as a result of
      diminished CD36-mediated FA uptake improves post-ischemic cardiac efficiency and
      functional recovery. As such, targeting cardiomyocyte FA uptake and FAO via
      inhibition of CD36 in the adult myocardium may provide therapeutic benefit during
      ischemia-reperfusion. 

PMID- 23948485
TI  - Central pontine myelinolysis following acute hypoglycemia.

PMID- 23948484
TI  - APpEaLINg therapeutic target for obesity cardiomyopathy?

PMID- 23948486
TI  - Physiological functions of phospholipase Cdelta1 and phospholipase Cdelta3.
AB  - Phospholipase C (PLC) is a key enzyme in phosphoinositide turnover, and in the
      regulation of various cellular events. Among the 13 PLC isozymes, PLCdelta1 and
      PLCdelta3 share a high sequence homology, and similar tissue distribution. Recent
      studies with genetically manipulated mice have clarified the importance of these
      PLC isozymes in a number of tissues. PLCdelta1 is required for maintenance of
      homeostasis in skin and metabolic tissues, while PLCdelta3 regulates microvilli
      formation in enterocytes and the radial migration of neurons in the cerebral
      cortex of the developing brain. Furthermore, simultaneous loss of PLCdelta1 and
      PLCdelta3 in mice causes placental vascular defects, leading to embryonic
      lethality. Taken together, PLCdelta1 and PLCdelta3 have unique and redundant
      roles in various tissues. 

PMID- 23948489
TI  - Theoretical study on photophysical properties of Pt(II) triarylborons with a 2,2
      bpy core derivatives.
AB  - The photophysical properties of the linear and v shaped Pt(II) triarylborons with
      a 2,2'-bpy core derivatives have been investigated by density functional theory
      (DFT) method. The calculated electronic absorption wavelengths are in agreement
      with experimental ones, which can be described as a mixed transition of intra
      ligand charge transfer (ILCT), ligand to ligand charge-transfer (LLCT), and metal
      to-ligand charge transfer (MLCT). It is found that the MLCT transition is mainly
      responsible for the low-energy absorption band with relative smaller oscillator
      strength, while the high-energy absorption band mainly derives from ILCT and LLCT
      transition. Moreover, the electron absorption wavelengths are not only dependent
      on the position of the Ph-BMes2 but also on the electron-accepting ability of the
      acceptor groups. The first hyperpolarizability values of the v shaped complexes
      are larger than that of the linear shape complex, which indicates that larger
      intramolecular charge transfer for the v shaped complexes will come into being
      under the external electric field. Moreover, these complexes exhibit two
      dimensional second-order nonlinear optical (NLO) character. Thus, the studied
      complexes have a possibility to be excellent second-order NLO materials. Based on
      the two-level model, the variation of first hyperpolarizabilities of the studied
      complexes can be explained by the combined effect of the difference between the
      ground state and excited state dipole moment, the oscillator strength, and the
      cube of the transition energy. 

PMID- 23948488
TI  - Retrieving clinical evidence: a comparison of PubMed and Google Scholar for quick
      clinical searches.
AB  - BACKGROUND: Physicians frequently search PubMed for information to guide patient
      care. More recently, Google Scholar has gained popularity as another freely
      accessible bibliographic database. OBJECTIVE: To compare the performance of
      searches in PubMed and Google Scholar. METHODS: We surveyed nephrologists (kidney
      specialists) and provided each with a unique clinical question derived from 100
      renal therapy systematic reviews. Each physician provided the search terms they
      would type into a bibliographic database to locate evidence to answer the
      clinical question. We executed each of these searches in PubMed and Google
      Scholar and compared results for the first 40 records retrieved (equivalent to 2
      default search pages in PubMed). We evaluated the recall (proportion of relevant
      articles found) and precision (ratio of relevant to nonrelevant articles) of the
      searches performed in PubMed and Google Scholar. Primary studies included in the
      systematic reviews served as the reference standard for relevant articles. We
      further documented whether relevant articles were available as free full-texts.
      RESULTS: Compared with PubMed, the average search in Google Scholar retrieved
      twice as many relevant articles (PubMed: 11%; Google Scholar: 22%; P<.001).
      Precision was similar in both databases (PubMed: 6%; Google Scholar: 8%; P=.07).
      Google Scholar provided significantly greater access to free full-text
      publications (PubMed: 5%; Google Scholar: 14%; P<.001). CONCLUSIONS: For quick
      clinical searches, Google Scholar returns twice as many relevant articles as
      PubMed and provides greater access to free full-text articles.

PMID- 23948487
TI  - Battle of the eternal rivals: restoring functional p53 and inhibiting Polo-like
      kinase 1 as cancer therapy.
AB  - Polo-like kinase 1, a pivotal regulator of mitosis and cytokinesis, is highly
      expressed in a broad spectrum of tumors and its expression correlates often with
      poor prognosis, suggesting its potential as a therapeutic target. p53, the
      guardian of the genome, is the most important tumor suppressor. In this review,
      we address the intertwined relationship of these two key molecules by fighting
      each other as eternal rivals in many signaling pathways. p53 represses the
      promoter of Polo-like kinase 1, whereas Polo-like kinase 1 inhibits p53 and its
      family members p63 and p73 in cancer cells lacking functional p53. Plk1
      inhibitors target all rapidly dividing cells irrespective of tumor cells or non
      transformed normal but proliferating cells. Upon treatment with Plk1 inhibitors,
      p53 in tumor cells is activated and induces strong apoptosis, whereas tumor cells
      with inactive p53 arrest in mitosis with DNA damage. Thus, inactive p53 is not
      associated with a susceptible cytotoxicity of Polo-like kinase 1 inhibition and
      could rather foster the induction of polyploidy/aneuploidy in surviving cells. In
      addition, compared to the mono-treatment, combination of Polo-like kinase 1
      inhibition with anti-mitotic or DNA damaging agents boosts more severe mitotic
      defects, effectually triggers apoptosis and strongly inhibits proliferation of
      cancer cells with functional p53. In this regard, restoration of p53 in tumor
      cells with loss or mutation of p53 will reinforce the cytotoxicity of combined
      Polo-like kinase 1 therapy and provide a proficient strategy for combating
      relapse and metastasis of cancer. 

PMID- 23948490
TI  - Potential role of allopregnanolone for a safe and effective therapy of
      neuropathic pain.
AB  - Because the treatment and management of neuropathic pain are extremely
      complicated, the characterization of novel analgesics and neuroprotectors with
      safe toxicological profiles is a crucial need to develop efficient therapies.
      Several investigations revealed that the natural neurosteroid allopregnanolone
      (AP) exerts analgesic, neuroprotective, antidepressant and anxiolytic effects.
      These effects result from AP ability to modulate GABA(A), glycine, L- and T-type
      calcium channels. It has been shown that AP treatment induced beneficial actions
      in humans and animal models with no toxic side effects. In particular, a multi
      parametric analysis revealed that AP efficiently counteracted chemotherapy-evoked
      neuropathic pain in rats. It has also been demonstrated that the modulation of AP
      producing enzyme, 3alpha-hydroxysteroid oxido-reductase (3alpha-HSOR), in the
      spinal cord regulates thermal and mechanical pain thresholds of peripheral nerve
      injured neuropathic rats. The painful symptoms were exacerbated by intrathecal
      injections of provera (pharmacological inhibitor of 3alpha-HSOR) which decreased
      AP production in the spinal cord. By contrast, the enhancement of AP
      concentration in the intrathecal space induced analgesia and suppression of
      neuropathic symptoms. Moreover, in vivo siRNA-knockdown of 3alpha-HSOR expression
      in healthy rat dorsal root ganglia increased thermal and mechanical pain
      perceptions while AP evoked a potent antinociceptive action. In humans, blood
      levels of AP were inversely associated with low back and chest pain. Furthermore,
      oral administration of AP analogs induced antinociception. Altogether, these data
      indicate that AP, which possesses a high therapeutic potential and a good
      toxicological profile, may be used to develop effective and safe strategies
      against chronic neuropathic pain.

PMID- 23948491
TI  - Ultrasound assisted the preparation of 1-butoxy-4-nitrobenzene under a new multi
      site phase-transfer catalyst--kinetic study.
AB  - In the present research work deals with the preparation of 1-butoxy-4
      nitrobenzene was successfully carried out by 4-nitrophenol with n-butyl bromide
      using aqueous potassium carbonate and catalyzed by a new multi-site phase
      transfer catalyst (MPTC) viz., N(1),N(4)-diethyl-N(1),N(1),N(4),N(4)
      tetraisopropylbutane-1,4-diammonium dibromide, under ultrasonic (40 kHz, 300 W)
      assisted organic solvent condition. The pseudo first-order kinetic equation was
      applied to describe the overall reaction. Under ultrasound irradiation (40 kHz,
      300 W) in a batch reactor, it shows that the overall reaction greatly enhanced
      with ultrasound irradiation than without ultrasound. The present study provides a
      method to synthesize nitro aromatic ethers by ultrasound assisted liquid-liquid
      multi-site phase-transfer catalysis condition.

PMID- 23948492
TI  - Acoustic cavitation structures produced by artificial implants of nuclei.
AB  - High-density controllable bubble structures are produced in the vicinity of
      radiating surface by artificially implant nuclei. Two kinds of typical cavitation
      structures produced by artificially implant nuclei are investigated. The focusing
      action and the physical origin of jet-induced cone-like bubble structure are
      analyzed. The sonochemical activity of cavitation structures is measured by using
      the standard method of potassium iodide dosimetry. The controllability of
      cavitation bubble cluster in the acoustic field is also discussed in this work. 

PMID- 23948493
TI  - Ultrasound-mediated drug delivery using liposomes modified with a thermosensitive
      polymer.
AB  - Ultrasound-mediated drug delivery was established using liposomes that were
      modified with the thermosensitive polymer (TSP) poly(NIPMAM-co-NIPAM), which
      sensitized the liposomes to high temperatures. TSP-modified liposomes (TSP
      liposomes) released encapsulated calcein under 1 MHz ultrasound irradiation at
      0.5 W/cm(2) for 120 s as well as the case under incubation at 42  degrees C for
      15 min. In addition, uptake of the drug released from TSP liposomes by cancer
      cells was enhanced by ultrasound irradiation. In a cell injury assay using
      doxorubicin (DOX)-loaded TSP liposomes and ultrasound irradiation, cell viability
      of HepG2 cells at 6 h after ultrasound irradiation (1 MHz, 0.5 W/cm(2) for 30 s)
      with DOX-loaded TSP liposomes (TSP/lipid ratio=1) was 60%, which was
      significantly lower than that of the control conditions such as DOX-loaded TSP
      liposomes alone and DOX-loaded intact liposomes under ultrasound irradiation.

PMID- 23948494
TI  - Influence of mixing and ultrasound frequency on antisolvent crystallisation of
      sodium chloride.
AB  - Ultrasound is known to promote nucleation of crystals and produce a narrower size
      distribution in a controlled and reproducible manner for the crystallisation
      process. Although there are various theories that suggest cavitation bubbles are
      responsible for sonocrystallisation, most studies use power ultrasonic horns that
      generate both intense shear and cavitation and this can mask the role that
      cavitation bubbles play. High frequency ultrasound from a plate transducer can be
      used to examine the effect of cavitation bubbles without the intense shear
      effect. This study reports the crystal size and morphology with various mixing
      speeds and ultrasound frequencies. The results show high frequency ultrasound
      produced sodium chloride crystals of similar size distribution as an ultrasonic
      horn. In addition, ultrasound generated sodium chloride crystals having a more
      symmetrical cubic structure compared to crystals produced by a high shear mixer. 

PMID- 23948495
TI  - Delay or deficit? Spelling processes in children with specific language
      impairment.
AB  - Few studies have explored the phonological, morphological and orthographic
      spellings skills of children with specific language impairment (SLI)
      simultaneously. Fifteen children with SLI (mean age=113.07 months, SD=8.61)
      completed language and spelling tasks alongside chronological-age controls and
      spelling-age controls. While the children with SLI showed a deficit in
      phonological spelling, they performed comparably to spelling-age controls on
      morphological spelling skills, and there were no differences between the three
      groups in producing orthographically legal spellings. The results also
      highlighted the potential importance of adequate non-word repetition skills in
      relation to effective spelling skills, and demonstrated that not all children
      with spoken language impairments show marked spelling difficulties. Findings are
      discussed in relation to theory, educational assessment and practice. LEARNING
      OUTCOMES: As a result of this activity, readers will describe components of
      spoken language that predict children's morphological and phonological spelling
      performance. As a result of this activity, readers will describe how the spelling
      skills of children with SLI compare to age-matched and spelling age-matched
      control children. Readers will be able to interpret the variability in spelling
      performance seen in children with SLI.

PMID- 23948496
TI  - Measuring psychological flexibility in medical students and residents: a
      psychometric analysis.
AB  - PURPOSE: Psychological flexibility involves mindful awareness of our thoughts and
      feelings without allowing them to prohibit acting consistently with our values
      and may have important implications for patient-centered clinical care. Although
      psychological flexibility appears quite relevant to the training and development
      of health care providers, prior research has not evaluated measures of
      psychological flexibility in medical learners. Therefore, we investigated the
      validity of our learners' responses to three measures related to psychological
      flexibility. METHODS: Fourth-year medical students and residents (n=275)
      completed three measures of overlapping aspects of psychological flexibility: (1)
      Acceptance and Action Questionnaire-II (AAQ-II); (2) Cognitive Fusion
      Questionnaire (CFQ); and (3) Mindful Attention and Awareness Questionnaire
      (MAAS). We evaluated five aspects of construct validity: content, response
      process, internal structure, relationship with other variables, and consequences.
      RESULTS: We found good internal consistency for responses on the AAQ
      (alpha=0.93), MAAS (alpha=0.92), and CFQ (alpha=0.95). Factor analyses
      demonstrated a reasonable fit to previously published factor structures. As
      expected, scores on all three measures were moderately correlated with one
      another and with a measure of life satisfaction (p<0.01). CONCLUSION: Our
      findings provide preliminary evidence supporting validity of the psychological
      flexibility construct in a medical education sample. As psychological flexibility
      is a central concept underlying self-awareness, this work may have important
      implications for clinical training and practice.

PMID- 23948497
TI  - Career advising in family medicine: a theoretical framework for structuring the
      medical student/faculty advisor interview.
AB  - BACKGROUND: There are unique challenges to recruiting students into the specialty
      of family medicine within academic medical centers. METHODS: At Virginia
      Commonwealth University, we developed an advising framework to help students
      address institutional and personal obstacles to choosing family medicine as a
      career. RESULTS: The role of a faculty advisor is not to direct the student to a
      career choice but rather to foster a mentor relationship and help the student
      come to his or her own realizations regarding career choice. The faculty
      advisor/medical student interview is conceptualized as five discussion topics:
      self-knowledge, perception, organizational voice, cognitive dissonance, and
      anticipatory counseling. CONCLUSION: This framework is intended to assist faculty
      in their efforts to encourage students to consider a career in family medicine.

PMID- 23948498
TI  - Traffic noise mapping of the city of Santiago de Chile.
AB  - A noise map is a cartographic representation of the noise level distribution in a
      determined area and period of time. This article presents the most important
      aspects of the noise mapping project across Santiago, a city of nearly six
      million inhabitants. The study was performed employing limited information and a
      low-cost, vehicular traffic noise predictive model. The methodology applied to
      the Chilean experience can also be used to create noise maps for major cities. An
      evaluation of noise prediction models, considering simplifications of the
      modeling environment (buildings) and for the vehicular traffic flow rates
      attributed to the streets under study, was made. The noise levels were modeled
      according to recommended exposure values for the above area. The results revealed
      that the noise levels for the city of Santiago were high in a relevant percentage
      of the surface. 

PMID- 23948499
TI  - pH and temperature effects on the hydrolysis of three beta-lactam antibiotics:
      ampicillin, cefalotin and cefoxitin.
AB  - An understanding of antibiotic hydrolysis rates is important for predicting their
      environmental persistence. Hydrolysis rates and Arrhenius constants were
      determined as a function of pH and temperature for three common beta-lactam
      antibiotics, ampicillin, cefalotin, and cefoxitin. Antibiotic hydrolysis rates at
      pH4-9 at 25  degrees C, 50  degrees C, and 60  degrees C were quantified, and
      degradation products were identified. The three antibiotics hydrolyzed under
      ambient conditions (pH7 and 25  degrees C); half-lives ranged from 5.3 to 27 d.
      Base-catalyzed hydrolysis rates were significantly greater than acid-catalyzed
      and neutral pH hydrolysis rates. Hydrolysis rates increased 2.5- to 3.9-fold for
      a 10  degrees C increase in temperature. Based on the degradation product masses
      found, the likely functional groups that underwent hydrolysis were lactam, ester,
      carbamate, and amide moieties. Many of the proposed products resulting from the
      hydrolysis of ampicillin, cefalotin, and cefoxitin likely have reduced
      antimicrobial activity because many products contained a hydrated lactam ring.
      The results of this research demonstrate that beta-lactam antibiotics hydrolyze
      under ambient pH and temperature conditions. Degradation of beta-lactam
      antibiotics will likely occur over several weeks in most surface waters and over
      several days in more alkaline systems.

PMID- 23948500
TI  - Predictive biomechanical analysis of ascending aortic aneurysm rupture potential.
AB  - Aortic aneurysm is a leading cause of death in adults, often taking lives without
      any premonitory signs or symptoms. Adverse clinical outcomes of aortic aneurysm
      are preventable by elective surgical repair; however, identifying at-risk
      individuals is difficult. The objective of this study was to perform a predictive
      biomechanical analysis of ascending aortic aneurysm (AsAA) tissue to assess
      rupture risk on a patient-specific level. AsAA tissues, obtained intra
      operatively from 50 patients, were subjected to biaxial mechanical and uniaxial
      failure tests to obtain their passive elastic mechanical properties. A novel
      analytical method was developed to predict the AsAA pressure-diameter response as
      well as the aortic wall yield and failure responses. Our results indicated that
      the mean predicted AsAA diameter at rupture was 5.6 +/- 0.7 cm, and the
      associated blood pressure to induce rupture was 579.4 +/- 214.8 mmHg. Statistical
      analysis showed significant positive correlation between aneurysm tissue
      compliance and predicted risk of rupture, where patients with a pressure-strain
      modulus >=100 kPa may be nearly twice as likely to experience rupture than
      patients with more compliant aortic tissue. The mechanical analysis of pre
      dissection patient tissue properties established in this study could predict the
      "future" onset of yielding and rupture in AsAA patients. The analysis results
      implicate decreased tissue compliance as a risk factor for AsAA rupture. The
      presented methods may serve as a basis for the development of a pre-operative
      planning tool for AsAA evaluation, a tool currently unavailable.

PMID- 23948501
TI  - Enzymatic conversion of D-galactose to D-tagatose: cloning, overexpression and
      characterization of L-arabinose isomerase from Pediococcus pentosaceus PC-5.
AB  - The gene encoding L-arabinose isomerase from food-grade strain Pediococcus
      pentosaceus PC-5 was cloned and overexpressed in Escherichia coli. The
      recombinant protein was purified and characterized. It was optimally active at 50
      degrees C and pH 6.0. Furthermore, this enzyme exhibited a weak requirement for
      metallic ions for its maximal activity evaluated at 0.6 mM Mn(2+) or 0.8 mM
      Co(2+). Interestingly, this enzyme was distinguished from other L-AIs, it could
      not use L-arabinose as its substrate. In addition, a three-dimensional structure
      of L-AI was built by homology modeling and L-arabinose and D-galactose were
      docked into the active site pocket of PPAI model to explain the interaction
      between L-AI and its substrate. The purified P. pentosaceus PC-5 L-AI converted D
      galactose into D-tagatose with a high conversion rate of 52% after 24 h at 50 
      degrees C, suggesting its excellent potential in D-tagatose production.

PMID- 23948502
TI  - Evaluation on an ergonomic design of functional clothing for wheelchair users.
AB  - Researchers have pointed out that people with physical disabilities find it
      difficult to obtain suitable clothing. In this study a set of wheelchair user
      oriented functional clothing was designed. Attention was paid to the wheelchair
      users' daily living activities related with clothing. An evaluating system
      combined with sports tournament and rehabilitation medicine was introduced to
      assess the new designed clothing. Six wheelchair users (3 males and 3 females)
      were invited to wear the clothing. A set of normal functional clothing was
      employed as a comparison (Control). The time required to complete three different
      daily living activities, i.e. dressing and undressing, going to toilet and
      bathing were recorded. Results showed that with the new clothing wheelchair
      users' competence of managing toilet was increased by 52.9%. The time needed for
      toilet was reduced by 45.7%. Their capability of managing dressing and undressing
      was improved by 24.6%. The study indicated that the newly designed clothing could
      facilitate wheelchair users' daily living activities related with clothing. 

PMID- 23948503
TI  - Advances in sociotechnical systems understanding and design: a Festschrift in
      honour of K.D. Eason.

PMID- 23948504
TI  - Long-term incidence of sensory disturbance in the forehead after fronto-orbital
      advancement in isolated nonsyndromic craniosynostosis.
AB  - In the majority of the craniofacial literature, preservation of the supraorbital
      nerve during fronto-orbital advancement (FOA) is recommended. However, only a few
      studies have evaluated the incidence of sensory disturbance in the forehead after
      FOA during long-term follow-up. 57 children who underwent FOA in their first year
      of life because of isolated nonsyndromic craniosynostosis including
      trigonocephaly, anterior plagiocephaly or oxycephaly, were evaluated for sensory
      disturbance in the frontal region with a minimum follow-up of 27 months. An
      objective and repeatable measurement using the Semmes-Weinstein test was possible
      in 36 children older than 5 years at last follow-up. We revealed no sensory
      deficits in all patients, even in 3 patients, where one of the supraorbital
      nerves was transected during FOA. As previous reports have suggested a full
      recovery of sensation after transection of the supraorbital nerve during FOA I
      seen, the need to preserve the nerve has to be evaluated. However, as release of
      the nerve from the supraorbital rim is possible, we generally recommend
      preserving this structure, to minimize the risk of sensory deficits in the
      forehead region. 

PMID- 23948505
TI  - Direct arthroscopic percutaneous resection of the Long Head of Biceps tendon.

PMID- 23948506
TI  - Activation of ClpP protease by ADEP antibiotics: insights from hydrogen exchange
      mass spectrometry.
AB  - The bacterial protease ClpP consists of 14 subunits that assemble into two
      stacked heptameric rings. The central degradation chamber can be accessed via
      axial pores. In free ClpP, these pores are obstructed by the N-terminal regions
      of the seven subunits at either end of the barrel. Acyldepsipeptides (ADEPs) are
      antibacterial compounds that bind in hydrophobic clefts surrounding the pore
      region, causing the pores to open up. The ensuing uncontrolled degradation of
      intracellular proteins is responsible for the antibiotic activity of ADEPs.
      Recently published X-ray structures yielded conflicting models regarding the
      conformation adopted by the N-terminal regions in the open state. Here, we use
      hydrogen/deuterium exchange (HDX) mass spectrometry to obtain complementary
      insights into the ClpP behavior with and without ADEP1. Ligand binding causes
      rigidification of the equatorial belt, accompanied by destabilization in the
      vicinity of the binding clefts. The N-terminal regions undergo rapid deuteration
      with only minor changes after ADEP1 binding, revealing a lack of stable H
      bonding. Our data point to a mechanism where the pore opening mechanism is
      mediated primarily by changes in the packing of N-terminal nonpolar side chains.
      We propose that a "hydrophobic plug" causes pore blockage in ligand-free ClpP.
      ADEP1 binding provides new hydrophobic anchor points that nonpolar N-terminal
      residues can interact with. In this way, ADEP1 triggers the transition to an open
      conformation, where nonpolar moieties are clustered around the rim of the pore.
      This proposed mechanism helps reconcile the conflicting models that had been put
      forward earlier. 

PMID- 23948507
TI  - Hsp90 inhibits alpha-synuclein aggregation by interacting with soluble oligomers.
AB  - Aggregated alpha-synuclein is one of the main components of the pathological Lewy
      bodies associated with Parkinson's disease (PD). Many other proteins, including
      chaperones such as Hsp90 and Hsp70, have been found co-localized with Lewy bodies
      and the expression levels of Hsp90 have been found to be increased in brains of
      PD patients. Although the role of Hsp70 in the aggregation of alpha-synuclein has
      been extensively studied, relatively little is known about the effect of Hsp90 on
      this process. Here, we have investigated if Hsp90 can prevent the aggregation of
      the A53T pathological mutant of alpha-synuclein in vitro. A detailed study using
      many biophysical methods has revealed that Hsp90 prevents alpha-synuclein from
      aggregating in an ATP-independent manner and that it forms a strong complex with
      the transiently populated toxic oligomeric alpha-synuclein species formed along
      the aggregation pathway. We have also shown that, upon forming a complex with
      Hsp90, the oligomers are rendered harmless and nontoxic to cells. Thus, we have
      clear evidence that Hsp90 is likely to play an important role on these processes
      in vivo. 

PMID- 23948508
TI  - In vivo feasibility study of ultrasound potentiated collagenase therapy of
      chronic total occlusions.
AB  - Arterial chronic total occlusions (CTOs) pose considerable challenges for
      percutaneous interventions, due primarily to the presence of stiff proximal
      fibrous caps (PFCs) which act as a barrier to the penetration of guide wires. A
      new approach under development for improving the success rate of guide wire
      crossing in CTOs is to employ collagenase to degrade the mechanical integrity of
      the PFCs. This has been shown to be feasible in preclinical work and in a Phase 1
      clinical trial. In a recent study we demonstrated using ex vivo experimental CTO
      specimens that ultrasound-stimulated microbubbles (USMBs) could potentiate the
      effects of collagenase and result in increased mechanical degradation of the PFCs
      of CTOs. Here we report the results of the first in vivo study examining the
      feasibility of this approach, which demonstrates that the force required to
      puncture through the PFCs of CTOs is reduced with combined USMB+collagenase
      treatments relative to collagenase only treatments. This approach has the
      potential to further improve the efficacy of the emerging technique of
      collagenase facilitation of percutaneous interventions for CTO. 

PMID- 23948509
TI  - Role of 18F-FDG PET/CT in diagnosing peritoneal carcinomatosis in the restaging
      of patient with ovarian cancer as compared to contrast enhanced CT and tumor
      marker Ca-125.
AB  - OBJECTIVES: To investigate the role of whole-body fluorine-18-2-deoxy-2-fluoro-d
      glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in
      the identification of peritoneal carcinomatosis in patients with ovarian cancer
      (OC). MATERIAL AND METHODS: Seventy-nine patients with histologically proven
      stages III-IV OC who underwent (18)F-FDG PET/CT were studied retrospectively. We
      considered group A as 51 patients who also underwent computed-tomography with
      contrast-enhancement (CECT), and group B as 35 patients who had also been tested
      for biomarker Ca-125. Sensitivity, specificity, accuracy, positive predictive
      values (PPV) and negative predictive values (NPV) of (18)F-FDG PET/CT as compared
      to CECT and to Ca-125 were evaluated. RESULTS: (18)F-FDG PET/CT' sensitivity,
      specificity, accuracy, PPV and NPV for all 79 patients were: 85%, 92.31%, 88.61%,
      91.89% and 85.71%, respectively. (18)F-FDG PET/CT sensitivity in group A was
      78.6%, while it was 53.6% for CECT. (18)F-FDG PET/CT specificity, calculated in
      the same group, was 91.3%, while that of CECT was 60.9% (statistically
      significant difference, McNemar 4, P=0.039). Accuracy was 84.3% and 56.9%,
      respectively. (18)F-FDG PET/CT' sensitivity in group B was 86.4%, while that of
      Ca-125 was 81.8% (no statistical difference, McNemar 0, P=1). (18)F-FDG PET/CT
      specificity in group B was 84.6% while that of Ca-125 was 38.5% (clear but not
      statistically significant difference, McNemar 3.12, P=0.070). Accuracy calculated
      in the same group was 85.7% for (18)F-FDG PET/CT and 65.7% for Ca-125.
      CONCLUSION: (18)F-FDG PET/CT is a useful diagnostic tool when peritoneal biopsy
      cannot be performed and it can better select those who are candidates for
      adjuvant chemotherapy.

PMID- 23948510
TI  - Pretreatment predictive factors for hepatitis C therapy outcome: relevance of
      anti-E1E2 antibodies compared to IP-10 and IL28B genotypes.
AB  - BACKGROUND: Unique serum anti-E1E2 antibodies were shown to be associated with
      spontaneous recovery or predictive of sustained virological response (SVR) in
      patients with chronic hepatitis C receiving pegylated interferon/ribavirin (PEG
      IFN/RBV) therapy. The objectives were to establish the relationship between
      pretreatment anti-E1E2 titres and HCV RNA kinetics during PEG-IFN/RBV therapy,
      and to examine whether the combined determination of interleukin (IL)28B
      rs12979860 and rs8099917, pretreatment inducible protein (IP)-10 levels and/or
      anti-E1E2 improved the prediction of SVR. METHODS: Sera from 26 treatment-naive
      consecutive HCV patients treated with PEG-IFN/RBV for 48 weeks were analysed.
      Serum anti-E1E2 titres and pretreatment IP-10 levels were measured by enzyme
      linked immunosorbent assays. The IL28B variants were determined using genotyping
      real-time polymerase chain reaction method. Viral decline was measured at weeks
      (W) 4 and 12 and SVR assessed 6 months after the end of therapy. RESULTS:
      Baseline anti-E1E2 titres were correlated with HCV RNA decline at W4 and W12 and
      were highly predictive of SVR with 100% of patients negative for anti-E1E2
      failing to achieve SVR. Receiver operating characteristic curve analyses indicate
      that the best prediction of SVR (AUC 0.990) was obtained with the combination of
      anti-E1E2 and IP-10 levels. Predictive values were better than those obtained
      with IP-10 alone or in combination with IL28B variants. CONCLUSIONS: Pretreatment
      serum anti-E1E2 response predicts HCV RNA clearance kinetics and treatment
      outcome. The combination of anti-E1E2 and IP-10 significantly improved the
      prediction of treatment response. This warrants further investigation and
      validation on larger cohorts of patients in the context of new therapeutic
      strategies.

PMID- 23948511
TI  - Diabetes mellitus-associated vascular impairment: novel circulating biomarkers
      and therapeutic approaches.
AB  - It is widely accepted that diabetes mellitus (DM) impairs endothelial nitric
      oxide synthase activity as well as enhances the production of reactive oxygen
      species, thus resulting in diminished nitric oxide bioavailability and the
      consequent pro-atherogenetic alterations. Important biomarkers of the vasculature
      are related to endothelial dysfunction, to inflammatory and coagulation
      processes, and to oxidative stress in DM. Several therapeutic strategies might
      exert favorable effects on the vasculature of diabetic patients, such as insulin
      analogues, antihypertensive agents, statins, and hypoglycemic agents, whereas in
      spite of the prominent role of oxidative stress in diabetes, antioxidant therapy
      remains controversial. The use of specific biomarkers related to vascular
      function could be a useful therapeutic approach in such patients. 

PMID- 23948512
TI  - The burgeoning epidemic of morbid obesity in patients undergoing percutaneous
      coronary intervention: insight from the Blue Cross Blue Shield of Michigan
      Cardiovascular Consortium.
AB  - OBJECTIVES: This study sought to examine the prevalence and clinical implications
      of morbid obesity among patients undergoing percutaneous coronary intervention
      (PCI). BACKGROUND: The prevalence of obesity, and morbid obesity in particular,
      continues to rise rapidly in the United States. Obese patients are at increased
      risk for cardiac disease and are more likely to need invasive cardiac procedures.
      There is a paucity of contemporary data on the prevalence and clinical
      implications of morbid obesity among patients undergoing PCI. METHODS: We
      examined the prevalence of morbid obesity (body mass index [BMI] >= 40 kg/m2)
      among 227,044 patients undergoing PCI and enrolled in the Blue Cross Blue Shield
      of Michigan Cardiovascular Consortium registry from 1998 to 2009. RESULTS: The
      proportion of morbidly obese patients undergoing PCI increased from 4.38% in 1998
      to 8.36% in 2009. Compared with overweight patients (BMI 25 to 30 kg/m2), these
      patients had significantly increased vascular complications (adjusted odds ratio
      [OR]: 1.31; 95% CI: 1.17 to 1.47; p < 0.0001), contrast-induced nephropathy
      (adjusted OR: 1.89; 95% CI: 1.70 to 2.11; p < 0.0001), nephropathy requiring
      dialysis (adjusted OR: 4.08; 95% CI: 2.98 to 5.59; p < 0.0001), and mortality
      (adjusted OR: 1.63; 95% CI: 1.33 to 2.00; p < 0.0001). CONCLUSIONS: Morbid
      obesity is increasing in prevalence among patients undergoing PCI and is
      associated with a higher risk of mortality and morbidity. These epidemiological
      changes have important implications for technical considerations of cardiac
      catheterization, design of the catheterization lab to accommodate these patients,
      and most importantly, for societal effort toward prevention of obesity.

PMID- 23948513
TI  - In-hospital outcomes of percutaneous coronary interventions in extremely obese
      and normal-weight patients: findings from the NCDR (National Cardiovascular Data
      Registry).
AB  - OBJECTIVES: The purpose of this study was to compare in-hospital outcomes of
      percutaneous coronary intervention (PCI) in extreme obesity (EO) (body mass index
      [BMI] >= 40 kg/m2) with those of normal-weight (NW) patients and to examine the
      influence of access site on outcomes. BACKGROUND: Little is known about the
      outcomes of PCI in EO patients. METHODS: We analyzed CathPCI Registry data from
      patients who underwent radial or femoral PCI and were discharged between July
      2009 and June 2011 and compared in-hospital outcomes of EO (N = 83,861) with
      those of NW patients (BMI 20 to 25 kg/m2; N = 217,616). Outcomes included in
      hospital mortality and procedural and bleeding complications. Multivariable
      logistic regression models were used to assess the independent association of EO
      with outcomes, using previously validated risk models derived from the CathPCI
      Registry. The role of access site was specifically examined. RESULTS: Compared
      with NW patients, EO patients were younger (median age 60 vs. 69 years), more
      likely female (47% vs. 37%), and more likely African American (12% vs. 7%). EO
      patients had lower unadjusted mortality (1.2% vs. 2.0%); however, after
      multivariable adjustment, EO was independently associated with increased risk of
      in-hospital mortality (odds ratio: 1.22; 95% CI: 1.08 to 1.39) in those
      presenting with ST-segment elevation myocardial infarction (STEMI). Access site
      had no effect on bleeding or outcome. CONCLUSIONS: EO patients who underwent PCI
      were younger and had less bleeding compared with NW patients. After multivariable
      adjustment for risk, EO was independently associated with higher in-hospital
      mortality overall and particularly in the patients undergoing STEMI.

PMID- 23948514
TI  - Evaluation of C-reactive protein before and on-treatment as a predictor of
      benefit of atorvastatin: a cohort analysis from the Anglo-Scandinavian Cardiac
      Outcomes Trial lipid-lowering arm.
AB  - OBJECTIVES: The aim of this study was to determine whether baseline and on-statin
      C-reactive protein (CRP) are independent predictors of cardiovascular (CV)
      outcome beyond low-density lipoprotein cholesterol (LDL-C). BACKGROUND: Use of
      CRP as a predictor of statin treatment remains controversial. METHODS: We
      investigated the relationship of baseline and on-treatment CRP with subsequent CV
      events in Cox models using a subset of white subjects with no history of CV
      disease from the UK ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial). RESULTS:
      During 5.5 years of follow-up, a total of 488 subjects experienced a CV event. CV
      risk increased with baseline CRP (hazard ratio [HR] per 1 SD: 1.21; 95%
      confidence interval [CI]: 1.09 to 1.33) in an adjusted model. In ASCOT Lipid
      Lowering Arm, the relative statin effect in preventing CV events did not differ
      according to tertiles of baseline CRP (p = 0.69). After 6 months of atorvastatin
      therapy, the median LDL-C and CRP were reduced by 38.7% and 25.8%, respectively.
      Those who achieved LDL-C below the median had a reduced CV risk (HR: 0.58; 95%
      CI: 0.34 to 0.97) compared with those who did not. In contrast, those who
      achieved a CRP level below the median did not have a reduced risk of CV events
      (HR: 0.95; 95% CI: 0.59 to 1.55). Among those who achieved LDL-C below the
      median, there was no difference in CV risk whether they also achieved a CRP level
      below (HR: 0.55; 95% CI: 0.30 to 1.02) or above the median (HR: 0.56; 95% CI:
      0.30 to 1.03). CONCLUSIONS: In these primary prevention patients, although
      baseline CRP independently predicted CV event risk, the achieved CRP level on
      while statin therapy did not predict CV events, either alone or in combination
      with LDL-C.

PMID- 23948515
TI  - ASK NOT what CRP can do for you.

PMID- 23948516
TI  - The perils of the last minute.

PMID- 23948517
TI  - Benign paroxysmal positional vertigo in Parkinson's disease.
AB  - BACKGROUND: Dizziness is a frequent complaint of patients with Parkinson's
      disease (PD), and orthostatic hypotension (OH) is often thought to be the cause.
      We studied whether benign paroxysmal positional vertigo (BPPV) could also be an
      explanation. AIM: To assess the prevalence of benign paroxysmal positional
      vertigo in patients with Parkinson's disease, with and without dizziness.
      METHODS: 305 consecutive outpatients with PD completed the Movement Disorders
      Society-sponsored revision of the Unified Parkinsons' Disease Rating Scale-motor
      score, the Dizziness Handicap Inventory, the Dix-Hallpike maneuver and a test for
      orthostatic hypotension. When positive for benign paroxysmal positional vertigo,
      a repositioning maneuver was performed. Patients were followed for three months
      to determine the clinical response. RESULTS: 305 patients responded (186 men
      (61%), mean age 70.5 years (Standard Deviation 9.5 years)), of whom 151 (49%)
      complained of dizziness. 57 (38%) of the dizzy patients appeared to have
      orthostatic hypotension; 12 patients (8%) had a classical but previously
      unrecognized benign paroxysmal positional vertigo. A further four patients (3%)
      had a more atypical presentation of benign paroxysmal positional vertigo. Three
      months after treatment, 11 (92%) of patients with classical benign paroxysmal
      positional vertigo were almost or completely without complaints. We found no
      'hidden' benign paroxysmal positional vertigo among patients without dizziness.
      The prevalence of benign paroxysmal positional vertigo among all patients with PD
      was 5.3%. CONCLUSION: Among Parkinson patients with symptoms of dizziness, up to
      11% may have benign paroxysmal positional vertigo, which can be treated easily
      and successfully.

PMID- 23948518
TI  - Chlorophyll fluorescence in the leaves of Tradescantia species of different
      ecological groups: induction events at different intensities of actinic light.
AB  - Chlorophyll fluorescence analysis is one of the most convenient and widespread
      techniques used to monitor photosynthesis performance in plants. In this work,
      after a brief overview of the mechanisms of regulation of photosynthetic electron
      transport and protection of photosynthetic apparatus against photodamage, we
      describe results of our study of the effects of actinic light intensity on
      photosynthetic performance in Tradescantia species of different ecological
      groups. Using the chlorophyll fluorescence as a probe of photosynthetic activity,
      we have found that the shade-tolerant species Tradescantia fluminensis shows a
      higher sensitivity to short-term illumination (<=20min) with low and moderate
      light (<=200MUEm(-2)s(-1)) as compared with the light-resistant species
      Tradescantia sillamontana. In T. fluminensis, non-photochemical quenching of
      chlorophyll fluorescence (NPQ) and photosystem II operational efficiency
      (parameter PhiPSII) saturate as soon as actinic light reaches ~200MUEm(-2)s(-1).
      Otherwise, T. sillamontana revealed a higher capacity for NPQ at strong light
      (>=800MUEm(-2)s(-1)). The post-illumination adaptation of shade-tolerant plants
      occurs slower than in the light-resistant species. The data obtained are
      discussed in terms of reactivity of photosynthetic apparatus to short-term
      variations of the environment light. 

PMID- 23948519
TI  - Can social semantic web techniques foster collaborative curriculum mapping in
      medicine?
AB  - BACKGROUND: Curriculum mapping, which is aimed at the systematic realignment of
      the planned, taught, and learned curriculum, is considered a challenging and
      ongoing effort in medical education. Second-generation curriculum managing
      systems foster knowledge management processes including curriculum mapping in
      order to give comprehensive support to learners, teachers, and administrators.
      The large quantity of custom-built software in this field indicates a shortcoming
      of available IT tools and standards. OBJECTIVE: The project reported here aims at
      the systematic adoption of techniques and standards of the Social Semantic Web to
      implement collaborative curriculum mapping for a complete medical model
      curriculum. METHODS: A semantic MediaWiki (SMW)-based Web application has been
      introduced as a platform for the elicitation and revision process of the Aachen
      Catalogue of Learning Objectives (ACLO). The semantic wiki uses a domain model of
      the curricular context and offers structured (form-based) data entry, multiple
      views, structured querying, semantic indexing, and commenting for learning
      objectives ("LOs"). Semantic indexing of learning objectives relies on both a
      controlled vocabulary of international medical classifications (ICD, MeSH) and a
      folksonomy maintained by the users. An additional module supporting the global
      checking of consistency complements the semantic wiki. Statements of the Object
      Constraint Language define the consistency criteria. We evaluated the application
      by a scenario-based formative usability study, where the participants solved
      tasks in the (fictional) context of 7 typical situations and answered a
      questionnaire containing Likert-scaled items and free-text questions. RESULTS: At
      present, ACLO contains roughly 5350 operational (ie, specific and measurable)
      objectives acquired during the last 25 months. The wiki-based user interface uses
      13 online forms for data entry and 4 online forms for flexible searches of LOs,
      and all the forms are accessible by standard Web browsers. The formative
      usability study yielded positive results (median rating of 2 ("good") in all 7
      general usability items) and produced valuable qualitative feedback, especially
      concerning navigation and comprehensibility. Although not asked to, the
      participants (n=5) detected critical aspects of the curriculum (similar learning
      objectives addressed repeatedly and missing objectives), thus proving the
      system's ability to support curriculum revision. CONCLUSIONS: The SMW-based
      approach enabled an agile implementation of computer-supported knowledge
      management. The approach, based on standard Social Semantic Web formats and
      technology, represents a feasible and effectively applicable compromise between
      answering to the individual requirements of curriculum management at a particular
      medical school and using proprietary systems.

PMID- 23948520
TI  - Mortality inequalities: Scotland versus England and Wales.
AB  - This paper is an observational study of particular historical trends in mortality
      inequality within Great Britain, comparing England and Wales with Scotland for
      the period 1925-2005. The inequalities in mortality within Great Britain have
      become more apparent over time. Growing inequality in premature mortality in
      Britain affected young Scottish men most severely after 1995. It would appear
      that something dramatic happened to the Scottish population in early 1970s which
      accelerated these broad and very important mortality differentials within Great
      Britain. The divergence in mortality within Great Britain is notable in
      successive male cohorts and to a lesser extent in women. 

PMID- 23948521
TI  - Electrophysiology of T-wave alternans: mechanisms and pharmacologic influences.
AB  - Extensive experimental evidence indicates a fundamental link between T-wave
      alternans (TWA) and arrhythmogenesis. Diverse physiologic and pathophysiologic
      influences alter TWA magnitude in parallel with their effects on vulnerability to
      ventricular tachyarrhythmias. Specifically, interventions that impede
      intracellular calcium handling, such as elevated heart rate, heightened
      adrenergic activity, myocardial ischemia, and heart failure, predispose to
      greater levels of TWA, reflecting heightened risk for arrhythmias. Conversely,
      vagus nerve stimulation, blockade of beta-adrenergic receptors and late sodium
      and L-type calcium channels, and sympathetic denervation decrease TWA magnitude,
      reflecting the potential of these interventions to reduce risk for ventricular
      tachycardia and fibrillation. TWA thus appears able to detect the influence of
      pathophysiologically relevant triggers as well as the efficacy of antiarrhythmic
      drugs without reducing the predictive capacity of the phenomenon. 

PMID- 23948522
TI  - New ST-segment elevation myocardial infarction criteria for left bundle branch
      block based on QRS area.
AB  - BACKGROUND: ECG detection of ST-segment elevation myocardial infarction (STEMI)
      in the presence of left bundle-branch block (LBBB) is challenging due to ST
      deviation from the altered conduction. The purpose of this study was to introduce
      a new algorithm for STEMI detection in LBBB and compare the performance to three
      existing algorithms. METHODS: Source data of the study group (143 with acute MI
      and 239 controls) comes from multiple sources. ECGs were selected by computer
      interpretation of LBBB. Acute MI reference was hospital discharge diagnosis.
      Automated measurements came from the Philips DXL algorithm. Three existing
      algorithms were compared, (1) Sgarbossa criteria, (2) Selvester 10% RS criteria
      and (3) Smith 25% S-wave criteria. The new algorithm uses an ST threshold based
      on QRS area. All algorithms share the concordant ST elevation and anterior ST
      depression criteria from the Sgarbossa score. The difference is in the threshold
      for discordant ST elevation. The Sgarbossa, Selvester, Smith and Philips
      discordant ST elevation criteria are (1) ST elevation >= 500 MUV, (2) ST
      elevation >= 10% of |S|-|R| plus STEMI limits, (3) ST elevation >= 25% of the S
      wave amplitude and (4) ST elevation >= 100 MUV + 1050 MUV/Ash * QRS area. The
      Smith S-wave and Philips QRS area criteria were tested using both a single and 2
      lead requirement. Algorithm performance was measured by sensitivity, specificity,
      and positive likelihood ratio (LR+). RESULTS: Algorithm performance can be
      organized in bands of similar sensitivity and specificity ranging from Sgarbossa
      score >= 3 with the lowest sensitivity and highest specificity, 13.3% and 97.9%,
      to the Selvester 10% rule with the highest sensitivity and lower specificity of
      30.1% and 93.2%. The Smith S-wave and Philips QRS area algorithms were in the
      middle band with sensitivity and specificity of (20.3%, 94.9%) and (23.8%, 95.8%)
      respectively. CONCLUSION: As can be seen from the difference between Sgarbossa
      score >= 3 and other algorithms for STEMI in LBBB, a discordant ST elevation
      criterion improves the sensitivity for detection but also results in a drop in
      specificity. For applications of automated STEMI detection that require higher
      sensitivity, the Selvester algorithm is better. For applications that require a
      low false positive rate such as relying on the algorithm for pre-hospital
      activation of cardiac catheterization laboratory for urgent PCI, it may be better
      to use the 2 lead Philips QRS area or Smith 25% S-wave algorithm.

PMID- 23948523
TI  - Phoenix dactylifera L. spathe essential oil: chemical composition and repellent
      activity against the yellow fever mosquito.
AB  - Date palm, Phoenix dactylifera L. (Arecaceae), grows commonly in the Arabian
      Peninsula and is traditionally used to treat various diseases. The aim of the
      present study was to identify chemical composition of the essential oil and to
      investigate the repellent activity. The essential oil of P. dactylifera was
      obtained by hydrodistillation from the spathe, a specialized leaf structure that
      surrounds the pollinating organs of the palm. The oil was subsequently analyzed
      by GC-FID and GC-MS. The oil showed promising repellent activity against yellow
      fever mosquito - Aedes aegypti. Sixteen components were characterized,
      constituting 99% of the oil. The main components were 3,4-dimethoxytoluene
      (73.5%), 2,4-dimethoxytoluene (9.5%), beta-caryophyllene (5.5%), p-cresyl methyl
      ether (3.8%), and caryophyllene oxide (2.4%). The minimum effective dosage (MED)
      for repellency for the P. dactylifera oil was 0.051mg/cm(2), which had moderately
      lower potency compared to reference standard N,N-diethyl-3-methylbenzamide, DEET
      (0.018mg/cm(2)) in the "cloth patch assay". The five major compounds were
      individually assayed for repellency to determine to what extent each is
      responsible for repellency from the oil. 3,4-Dimethoxytoluene and 2,4
      dimethoxytoluene showed the best repellent activity with the same MED value of
      0.063mg/cm(2), respectively. The results indicate that these two constituents
      which comprise a large proportion of the P. dactylifera oil (83%) are likely
      responsible for the observed repellent activity. In this aspect, the P.
      dactylifera spathe oil is a sustainable, promising new source of natural
      repellents. 

PMID- 23948524
TI  - Editor's corner: DSM-5--ready or not, here it comes.

PMID- 23948525
TI  - A twin study of alcohol dependence, binge eating, and compensatory behaviors.
AB  - OBJECTIVE: Rates of alcohol dependence are elevated in women with eating
      disorders who engage in binge eating or compensatory behaviors compared with
      women with eating disorders who do not report binge eating or compensatory
      behaviors and with healthy controls. Alcohol dependence, binge eating, and
      compensatory behaviors are heritable; however, it is unclear whether a shared
      genetic liability contributes to the phenotypic association among these traits,
      and little information exists regarding this shared liability in men. We
      investigated genetic and environmental correlations among alcohol dependence,
      binge eating, and compensatory behaviors in male and female twins. METHOD:
      Participants included 5,993 same- and opposite-sex twins from the Australian Twin
      Registry who completed a modified version of the Semi-Structured Assessment for
      the Genetics of Alcoholism that assessed lifetime alcohol dependence and binge
      eating as defined in the Diagnostic and Statistical Manual of Mental Disorders,
      Third Edition, Revised. Compensatory behaviors were assessed via a general health
      questionnaire in women only. Biometrical twin models estimated genetic and
      environmental influences on alcohol dependence, binge eating, and compensatory
      behaviors. RESULTS: In women, the multivariate twin model suggested that additive
      genetic and nonshared environmental effects influenced alcohol dependence, binge
      eating, and compensatory behaviors, with heritability estimates ranging from 38%
      to 53%. The best-fitting sex-limitation model was a common effects model that
      equated all genetic and nonshared environmental influences in men and women. The
      heritability estimates were 50% and 38% for alcohol dependence and binge eating,
      respectively. Overall, there were significant genetic correlations between
      alcohol dependence and binge eating, alcohol dependence and compensatory
      behaviors, and binge eating and compensatory behaviors. CONCLUSIONS: These
      findings indicate that common genetic factors may underlie the vulnerability to
      alcohol dependence and the liability to binge eating and compensatory behaviors.

PMID- 23948526
TI  - Impact of fathers' alcohol problems on the development of effortful control in
      early adolescence.
AB  - OBJECTIVE: This article examines the association between fathers' alcohol
      problems and children's effortful control during the transition from middle
      childhood to early adolescence (fourth to sixth grade). Additionally, we examined
      the role of two potential moderators of this association, fathers' antisocial
      behavior and child gender. METHOD: The sample consisted of 197 families (102
      nonalcoholic [NA]; 95 father alcoholic [FA], in which only the father met
      diagnostic criteria for alcohol abuse or dependence). The sample was recruited
      from New York State birth records when the children were 12 months old. This
      analysis focused on 12-month alcohol problem data and child effortful control
      data measured in the fourth and sixth grades. RESULTS: Structural equation
      modeling revealed that FA status was associated with lower effortful control on
      the Stroop Color and Word and Tower of London tasks in the sixth grade, but
      antisocial behavior did not moderate this association. Multiple group analysis
      revealed that FA status was associated with higher Stroop interference scores in
      fourth and sixth grade and lower move scores on the Tower of London task for boys
      but not girls. CONCLUSIONS: The association between FA status and effortful
      control may be attenuated in middle childhood (fourth grade) but emerge again in
      early adolescence (sixth grade). The results indicate that sons of alcoholics may
      be particularly vulnerable to poor self-regulatory strategies and that early
      adolescence may be an important time for intervening with these families to
      facilitate higher self-regulation before the transition to high school.

PMID- 23948527
TI  - Alcohol-specific parenting as a mechanism of parental drinking and alcohol use
      disorder risk on adolescent alcohol use onset.
AB  - OBJECTIVE: The primary aim of the current study was to examine three dimensions
      of alcohol-specific parenting (anti-alcohol parenting strategies, parental
      legitimacy in regulating adolescent drinking, and parental disclosure of negative
      alcohol experiences) as mechanisms in the prospective relations between parental
      drinking and alcohol use disorder (recovered, current, and never diagnosed) and
      adolescent alcohol use initiation. METHOD: Participants were from an ongoing
      longitudinal study of the intergenerational transmission of alcoholism.
      Structural equation modeling was used to test a maternal model (n = 268
      adolescents and their mothers) and a paternal model (n = 204 adolescents and
      their fathers) of alcohol-specific parenting. RESULTS: Results indicated that
      higher levels of drinking among mothers and current alcohol use disorder among
      fathers were related to more frequent parental disclosure of personal negative
      experiences with alcohol. Maternal disclosure of negative alcohol experiences
      mediated the effect of maternal drinking on adolescent onset of alcohol use such
      that more disclosure predicted a greater likelihood of adolescent drinking
      initiation at follow-up over and above general parenting. In addition, currently
      alcoholic mothers were perceived as having less legitimate authority to regulate
      adolescent drinking, and low levels of legitimacy among fathers was predictive of
      drinking onset among adolescents. CONCLUSIONS: Alcohol-specific parenting is a
      distinct and influential predictor of adolescent alcohol use initiation that is
      partially shaped by parents' own drinking experiences. Moreover, parental
      conversations about their own personal experiences with alcohol may not represent
      a form of parent-child communication about drinking that deters adolescent
      drinking.

PMID- 23948528
TI  - Parental socialization and children's susceptibility to alcohol use initiation.
AB  - OBJECTIVE: This study examined relations between children's susceptibility to
      alcohol use initiation and parents' alcohol-specific beliefs, attitudes, and
      practices and whether these relations vary by parental alcohol use. METHOD: The
      sample comprised 1,050 pairs of mothers or mother surrogates and their third
      grade children (51.8% female) recruited for a 4-year intervention trial. Families
      were recruited from school districts located primarily in North Carolina; the
      school districts provided permission for study recruitment materials to be
      distributed to families but were not otherwise involved in the research. Data are
      from the baseline cross-sectional telephone interviews conducted with the mothers
      and children. Children's susceptibility to alcohol use initiation is based on
      child reports, and parental alcohol-specific beliefs, attitudes, and practices
      are based on maternal reports. RESULTS: All parental alcohol socialization
      attributes were statistically significantly associated as hypothesized with child
      susceptibility to alcohol use initiation. In the final full model, the mother's
      disapproving attitude about child sipping and the interaction between mother
      child communication and parental alcohol use frequency were uniquely
      significantly associated with child susceptibility. Talking with the child about
      harmful consequences of alcohol use was associated with reduced child
      susceptibility in families where parents drank alcohol more frequently but had no
      relationship with child susceptibility in families where parents drank
      infrequently. CONCLUSIONS: The normative interactions that parents have with
      their elementary school children may inhibit or facilitate children's
      susceptibility to alcohol use. To the extent that child susceptibility leads to
      early onset of use, prevention programs directed at parents to reduce child
      susceptibility are indicated.

PMID- 23948529
TI  - Causal influence of age at first drink on alcohol involvement in adulthood and
      its moderation by familial context.
AB  - OBJECTIVE: Previous research has established a connection between early age at
      drinking initiation and greater alcohol involvement in adulthood, but it has not
      yet been established whether this is a causal effect. The current study used a
      multilevel discordant twin design to examine individual and contextual effects,
      and an interaction between these effects, of the age at drinking initiation on
      the frequency and quantity of drinking in adulthood. METHOD: Participants were
      4,194 same-sex twins (2,264 monozygotic, 1,924 dizygotic; 2,270 women; Mage =
      29.9 years) from the Australian Twin Registry who completed a telephone interview
      that included assessments of the age at alcohol use initiation and past-year
      frequency and quantity of alcohol use. Multilevel models were estimated using
      data from the full sample and using data from only monozygotic twins. Individual
      (within-twin-pair comparison) and family contextual (between-twin-pair
      comparison) effects were estimated. RESULTS: The age at first drink was related
      to the past-year frequency (r = -.16) and quantity of drinking (r = -.12) in
      young adulthood. Individual (causal) and family context effects of age at
      drinking onset predicted later adult drinking frequency and quantity. There was
      also a significant cross-level interaction between individual and family contexts
      for frequency but not quantity of drinking. CONCLUSIONS: Results of this study
      indicate a potential causal effect of age at drinking onset on adult alcohol
      involvement as well as the importance of examining both individual and contextual
      effects in discordant twin studies.

PMID- 23948530
TI  - Adolescent athletic participation and nonmedical Adderall use: an exploratory
      analysis of a performance-enhancing drug.
AB  - OBJECTIVE: A primary motive for adolescents and young adults to nonmedically use
      prescription stimulants is to help them study. Adolescents and young adults are
      using prescription stimulants, such as Adderall (amphetamine aspartate,
      amphetamine sulfate, dextroamphetamine saccharate, dextroamphetamine sulfate), as
      performance enhancers in certain social domains, including academics and sports.
      The purpose of this exploratory study was to examine the nonmedical use of
      Adderall (a commonly prescribed stimulant used nonmedically) among adolescents
      who participate in competitive sports. METHOD: The Monitoring the Future survey
      for 2010 and 2011, a representative sample of 8th- and 10th-grade students,
      surveyed involvement in competitive sports and nonmedical Adderall use among
      21,137 adolescents. Past-year nonmedical use of Adderall served as the main
      outcome measure. Logistic regression analyses were run to examine whether sports
      participation in general and involvement in different types of competitive sports
      participation were associated with past-year nonmedical use of Adderall among
      males and females. RESULTS: The odds of past-year nonmedical use of Adderall
      among males were higher for male respondents who participated in lacrosse
      (adjusted odds ratio [AOR] = 2.52, 95% CI [1.20, 5.29]) and wrestling (AOR =
      1.74, 95% CI [1.01, 2.98]). However, no particular sport among females was found
      to be associated with past-year nonmedical use of Adderall. CONCLUSIONS: Certain
      extracurricular activities, such as high-contact sports, may influence male
      participants to misuse prescription stimulants as performance enhancers either on
      or off the playing field.

PMID- 23948531
TI  - College cannabis use: the unique roles of social norms, motives, and
      expectancies.
AB  - OBJECTIVE: Given that the majority of college cannabis use occurs in social
      situations, descriptive norms (beliefs about others' use) and injunctive norms
      (others' approval of risky use) may be particularly relevant to cannabis-related
      behaviors. Yet, little research has examined the unique impact of these norms on
      one's own behaviors when accounting for the variance attributable to other
      relevant cognitive factors. The current study is the first known investigation of
      the unique impact of social norms, cannabis use motives, and cannabis effect
      expectancies on cannabis use. METHOD: Data came from 223 (64.1% female) current
      cannabis-using undergraduates who completed an online questionnaire in exchange
      for psychology-course research credit. RESULTS: Descriptive norms regarding
      friends (not students in general) and injunctive norms (friends and parents) were
      related to cannabis use frequency. Descriptive norms (friends, not students in
      general) and injunctive norms (friends, not parents) were related to cannabis
      problems. Relevant norms, expectancies, and motives accounted for 66.8% of the
      variance in cannabis use frequency and 28.7% of the variance in cannabis
      problems. In multivariate analyses, descriptive norms (friends) accounted for the
      greatest amount of unique variance in cannabis use frequency, whereas coping
      motives accounted for the greatest amount of unique variance in cannabis-related
      problems. CONCLUSIONS: Descriptive norms (friends) and coping motives may be two
      cognitive vulnerability factors that could be particularly important targets for
      interventions.

PMID- 23948532
TI  - Transitional life events and trajectories of cigarette and alcohol use during
      emerging adulthood: latent class analysis and growth mixture modeling.
AB  - OBJECTIVE: Emerging adulthood (ages 18-25 years) has been associated with
      elevated substance use. Transitional life events (TLEs) during emerging adulthood
      in relation to substance use are usually examined separately, rather than as a
      constellation. The purposes of this study were (a) to explore distinct subgroups
      experiencing various TLEs during emerging adulthood, (b) to identify
      heterogeneous trajectories of cigarette and alcohol use during emerging
      adulthood, and (c) to examine the association of TLEs with cigarette and alcohol
      use trajectories. METHOD: Five waves of longitudinal data (mean age range: 19.5
      26.0 years) were used from a community-based drug prevention program (n = 946,
      49.9% female). Distinct subgroups of emerging adults who experienced various TLEs
      were identified using latent class analysis. Cigarette and alcohol use were
      examined using a latent growth mixture model. RESULTS: A three-class model fit
      the data best in identifying TLE subgroups (new family, college attenders [NFCA];
      uncommitted relationships, college attenders [URCA]; hibernators [HBN]). Three
      trajectory models fit the data best for cigarette and alcohol use during emerging
      adulthood. The TLE categories were significantly associated with the cigarette (p
      < .05) and alcohol use groups (p < .001); specifically, the URCA and HBN groups
      were significantly more likely to be classified as accelerating cigarette users,
      relative to NFCA (ps < .05). The NFCA and HBN groups were significantly more
      likely to be classified as accelerating alcohol users, relative to URCA (ps <
      .01). CONCLUSIONS: To characterize an "at-risk" emerging adult group for
      cigarette and alcohol use over time, a range of life events during emerging
      adulthood should be considered. Interventions tailored to young adulthood may
      benefit from targeting the absence of these life events typifying "independence"
      as a potential marker for underlying substance use problems and provide
      supplemental screening methods to identify young adults with similar issues.

PMID- 23948533
TI  - Perceived norms moderate the association between mental health symptoms and
      drinking outcomes among at-risk adolescents.
AB  - OBJECTIVE: There has been limited research examining the association between
      mental health symptoms, perceived peer alcohol norms, and alcohol use and
      consequences among samples of adolescents. The current study used a sample of 193
      at-risk youths with a first-time alcohol and/or other drug offense in the
      California Teen Court system to explore the moderating role of perceived peer
      alcohol norms on the association between mental health symptoms and drinking
      outcomes. METHOD: Measures of drinking, consequences, mental health symptoms, and
      perceived peer alcohol norms were taken at baseline, with measures of drinking
      and consequences assessed again 6 months later. Regression analyses examined the
      association of perceived norms and mental health symptoms with concurrent and
      future drinking and consequences. RESULTS: We found that higher perceived
      drinking peer norms were associated with heavy drinking behavior at baseline and
      with negative alcohol consequences both at baseline and 6 months later. Also,
      perceived drinking norms moderated the association between mental health symptoms
      and alcohol-related consequences such that better mental health was related to
      increased risk for alcohol-related consequences both concurrently and 6 months
      later among those with higher baseline perceptions of peer drinking norms.
      CONCLUSIONS: Findings demonstrate the value of norms-based interventions,
      especially among adolescents with few mental health problems who are at risk for
      heavy drinking.

PMID- 23948534
TI  - Early risk factors for alcohol use across high school and its covariation with
      deviant friends.
AB  - OBJECTIVE: Past research has associated childhood characteristics and experiences
      with alcohol use at single time points in adolescence. Other work has focused on
      drinking trajectories across adolescence but with risk factors typically no
      earlier than middle or high school. Similarly, although the connection between
      underage drinking and affiliation with deviant friends is well established, early
      risk factors for their covariation across adolescence are uncertain. The present
      study examines the influence of early individual and contextual factors on (a)
      trajectories across high school of per-occasion alcohol use and (b) the
      covariation of alcohol use and deviant friends over time. METHOD: In a
      longitudinal community sample (n = 374; 51% female), temperamental disinhibition,
      authoritarian and authoritative parenting, and parental alcohol use were assessed
      during childhood, and adolescents reported on alcohol use and affiliation with
      deviant friends in the spring of Grades 9, 10, 11, and 12. RESULTS: Early
      parental alcohol use predicted the intercept of adolescent drinking. Subsequent
      patterns of adolescent alcohol use were predicted by sex and interactions of sex
      and childhood disinhibition with early authoritarian parenting. Additionally,
      childhood disinhibition interacted with parental alcohol use to moderate the
      covariation of drinking and deviant friends. CONCLUSIONS: These findings
      highlight early individual and contextual risk factors for alcohol use across
      high school, extending previous work and underscoring the importance of
      developmental approaches and longitudinal techniques for understanding patterns
      of growth in underage drinking.

PMID- 23948535
TI  - Is the pregame to blame? Event-level associations between pregaming and alcohol
      related consequences.
AB  - OBJECTIVE: Pregaming (drinking before a social occasion) predicts alcohol
      consequences between persons; people who pregame report greater consequences than
      those who do not. The present study examined within-person associations between
      pregaming and daily consequences. METHOD: Participants were college students (N =
      44; 50% female) reporting past-month pregaming. Daily drinks consumed (during
      pregaming and across the entire drinking episode) and alcohol consequences were
      assessed with a 30-day Timeline Followback interview. RESULTS: Within
      individuals, engaging in pregaming predicted consequences experienced on a given
      day above and beyond the number of drinks consumed across the drinking episode
      and typical drinking level. Furthermore, there was a trend toward pregaming
      placing women at more risk for consequences than men. CONCLUSIONS: Findings
      support a context-specific risk for consequences that is conferred by pregaming
      and that is independent of how much drinking occurs across the drinking episode.
      Results highlight pregaming as a target for future interventions.

PMID- 23948536
TI  - Identifying theoretical predictors of risky alcohol use among noncollege emerging
      adults.
AB  - OBJECTIVE: Studies show that emerging adults who do not obtain postsecondary
      education are at greater risk for developing alcohol use disorders later in life
      relative to their college-attending peers. Research examining constructs amenable
      to change within this population is necessary to inform intervention efforts.
      Thus, the current study aimed to identify psychosocial correlates of risky
      alcohol use for noncollege emerging adults. A secondary goal was to examine
      whether gender moderated the relationships between the psychosocial constructs
      and alcohol use. METHOD: Participants were a nationally representative sample of
      noncollege emerging adults (18-22 years old) who reported using alcohol in the
      past year, recruited through an established Internet panel (N = 209; 125 women).
      A path model was used to examine the relationship between theoretically derived
      constructs (expectancies, attitudes, normative beliefs) and risky (peak)
      drinking. A second model examined a multigroup solution to assess moderating
      effects of gender. RESULTS: The full-sample model revealed significant
      associations between attitudes toward drinking and risky drinking. The model
      assessing gender differences revealed association between normative beliefs and
      drinking for women but not men, whereas attitudes were significantly associated
      with risky drinking for both men and women. CONCLUSIONS: Findings highlight the
      importance of attitudes and, for women, descriptive norms in the etiology of
      risky drinking among noncollege emerging adults, which emphasizes their potential
      utility in the development and adaptation of interventions for this at-risk
      population.

PMID- 23948537
TI  - Treatment may influence self-report and jeopardize our understanding of outcome.
AB  - OBJECTIVE: Standardized measures of self-reported alcohol use are the predominant
      method by which change in alcohol use following interventions is evaluated. This
      study examined whether the invariance of the test-retest pretreatment Alcohol Use
      Disorders Identification Test (AUDIT) was affected by the treatment experience.
      In this study, the intervening exposure was to motivational interviewing (MI)
      versus community service (CS), the treatment-as-usual control group. METHOD:
      Analyses were conducted on a subsample of court-referred 16- to 21-year-olds
      recruited into a randomized controlled trial examining the effects of MI on
      alcohol use and police charges for risky driving and/or drinking. Youths were
      randomized to CS or MI. A subsample of 478 participants, who at baseline
      completed the AUDIT in reference to alcohol use for the 6 months before their
      conviction, later repeated the AUDIT at treatment completion, in reference to the
      same 6-month baseline period. RESULTS: At completion of treatment, participants
      receiving CS had a significant decrease in baseline AUDIT scores, whereas those
      in MI reported no significant change. The difference between the two groups was
      significant (p = .02). Also, of those who reported no drinking before treatment,
      after receiving MI, 33.5% changed their response and acknowledged pretreatment
      drinking, compared with only 8.3% in CS. CONCLUSIONS: These results suggest that
      treatment received may differentially affect a standardized measure of self
      reported risky drinking. This effect may be attributable to the treatment
      experience and/or the experience of the control group. Possible explanations for
      the effect are explored, including more honesty because of a trusting therapeutic
      alliance and a response shift bias. Differential change in self-report might
      affect treatment outcome assessment. Depending on the treatment contrasts,
      research that relies on pre- to post-treatment changes in self-report may be
      underestimating treatment effects.

PMID- 23948538
TI  - Characterizing college systems for addressing student alcohol use: latent class
      analysis of U.S. four-year colleges.
AB  - OBJECTIVE: The purpose of this study was to assess the status and integration of
      college systems to address student alcohol use. METHOD: We conducted a survey of
      college leaders (campus administrators, healthcare directors, and enforcement
      directors) among 569 4-year colleges in the United States. We measured strategies
      across five key system components: policy, enforcement, education, screening, and
      intervention/treatment. We used latent class analyses to identify classes of
      colleges based on their alcohol systems. RESULTS: We identified three classes of
      colleges. Thirty-four percent of colleges were in a class that was characterized
      as having the most strategies relative to the other colleges, including high
      probabilities for having one of the three policy strategies, both enforcement
      strategies, two of the three screening strategies, and both intervention
      strategies. Class 2 colleges were similar to Class 1 colleges but had very low
      probabilities of having the intervention strategies. Thirty percent of the
      colleges were in Class 3; these colleges had a low probability of having any of
      the strategies except two of the three policy strategies. CONCLUSIONS: Many of
      the colleges had implemented strategies to address student alcohol use across
      multiple system components, although no class of colleges had implemented all of
      the identified strategies in each of the five components. Many colleges failed to
      use complementary strategies, such as having screening but no treatment or
      intervention services. More research is needed to assess whether class membership
      is associated with rates of student alcohol use and related problems.

PMID- 23948541
TI  - Factor structure of the modified Timeline Followback: a measure of alcohol
      related consequences.
AB  - OBJECTIVE: Knowledge of the types of consequences assessed by a given measure of
      alcohol-related consequences is important, as it may affect how the scores from
      that measure relate to individual differences and how the measure is used in
      treatment. This study was designed to examine the factor structure of the
      modified Timeline Followback (TLFB). METHOD: Undergraduate students (n = 573;
      68.9% female) who drank alcohol at least once in the past 30 days completed an
      online version of the modified TLFB, a measure of alcohol use and alcohol-related
      consequences. RESULTS: A confirmatory factor analysis supported the previously
      proposed four-factor structure of the consequences assessed by the modified TLFB
      (i.e., personal, social, role functioning, and physical consequences). Internal
      consistency of the four categories, as assessed by deleted-item odds ratios, was
      good. Additionally, correlations between subscale scores and measures of alcohol
      use provided evidence of convergent validity, and intraclass correlations between
      two administration formats (online vs. in-person) indicated preliminary
      concurrent validity of the four factors. CONCLUSIONS: Overall, this study found
      support for the factor structure that was previously proposed by Norberg et al.
      Both the results of the confirmatory factor analysis and the deleted-item odds
      ratios indicate that most items fit the model well. Four items, however, could
      not be included in the model as a result of either low endorsement or poor fit,
      suggesting that further research on these items is needed.

PMID- 23948540
TI  - Craving and subjective responses to alcohol administration: validation of the
      desires for alcohol questionnaire in the human laboratory.
AB  - OBJECTIVE: The abbreviated Desires for Alcohol Questionnaire (DAQ) is a self
      report assessment of craving comprising the following subscales: (a) strong
      desires/intentions to drink, (b) negative reinforcement, and (c) positive
      reinforcement and ability to control drinking. Although the DAQ is sensitive to
      changes in alcohol craving precipitated by alcohol administration and/or cue
      exposure, no studies to date have examined the relationship between DAQ scores
      and subjective responses to alcohol. This study addresses this gap in the
      literature by testing the relationship between subjective responses to alcohol
      during alcohol administration and DAQ scores assessed 1 month later. METHOD:
      Individuals with alcohol dependence (n = 32) completed a randomized, single
      blinded, intravenous alcohol administration in the laboratory in which subjective
      responses to the alcohol were measured, followed by a visit to the laboratory 1
      month later to complete the DAQ. RESULTS: Analyses revealed robust associations
      between DAQ scores and alcohol craving during alcohol administration (partial
      correlations: r = .43-.50, ps < .01), with the exception of the positive
      reinforcement subscale (r = .20, p = .30). Subjective intoxication and sedation
      were only associated with the negative reinforcement subscale of the DAQ (r =
      .38, p < .05 and r = .33, p < .05, respectively). CONCLUSIONS: Craving, captured
      by the DAQ, is reliably and positively associated with alcohol-induced craving.
      The DAQ is also associated with specific dimensions of subjective responses to
      alcohol. These results support the clinical utility of the DAQ, particularly in
      large samples where experimental manipulations may not be feasible.

PMID- 23948539
TI  - Potential side effects of unhealthy lifestyle choices and health risks on basal
      and reactive heart rate variability in college drinkers.
AB  - OBJECTIVE: Emerging adults often begin making independent lifestyle choices
      during college, yet the association of these choices with fundamental indicators
      of health and adaptability is unclear. The present study examined the
      relationship between health risks and neurocardiac function in college drinkers.
      METHOD: Heart rate variability (HRV) was assessed at baseline and in reaction to
      a paced breathing challenge in 212 college drinkers (53.8% women). Basal HRV
      served as a general indicator of health. Reactive HRV (during paced breathing)
      was used as a marker of an individual's adaptability to challenge. The
      relationship of HRV to alcohol use, cigarette use, exercise, sleep, and body mass
      index (BMI) was assessed. RESULTS: Greater alcohol use and less exercise were
      associated with lower basal HRV. BMI was unrelated to basal HRV but was
      negatively associated with reactive HRV during the breathing challenge.
      CONCLUSIONS: High levels of alcohol use and lack of exercise are negative
      correlates of cardiovascular and general health, even in apparently healthy
      college drinkers. The negative relationship between BMI and reactive HRV suggests
      that overweight individuals have reduced ability to psychophysiologically adapt
      to challenges; understanding the temporal course of this relationship is needed.
      This study highlights the importance of examining HRV at baseline and in response
      to a challenge to capture the active neurocardiac processes that contribute to
      health and adaptive responding. The suppressive effects of health risks on HRV
      are modifiable; thus, HRV may be useful in evaluating the health benefits of
      lifestyle change and in promoting change behaviors in college drinkers.

PMID- 23948542
TI  - Brief report: The Brief Alcohol Social Density Assessment (BASDA): convergent,
      criterion-related, and incremental validity.
AB  - OBJECTIVE: Alcohol misuse is substantially influenced by social factors, but
      systematic assessments of social network drinking are typically lengthy. The goal
      of the present study was to provide further validation of a brief measure of
      social network alcohol use, the Brief Alcohol Social Density Assessment (BASDA),
      in a sample of emerging adults. Specifically, the study sought to examine the
      BASDA's convergent, criterion, and incremental validity in relation to well
      established measures of drinking motives and problematic drinking. METHOD:
      Participants were 354 undergraduates who were assessed using the BASDA, the
      Alcohol Use Disorders Identification Test (AUDIT), and the Drinking Motives
      Questionnaire. RESULTS: Significant associations were observed between the BASDA
      index of alcohol-related social density and alcohol misuse, social motives, and
      conformity motives, supporting convergent validity. Criterion-related validity
      was supported by evidence that significantly greater alcohol involvement was
      present in the social networks of individuals scoring at or above an AUDIT score
      of 8, a validated criterion for hazardous drinking. Finally, the BASDA index was
      significantly associated with alcohol misuse above and beyond drinking motives in
      relation to AUDIT scores, supporting incremental validity. CONCLUSIONS: Taken
      together, these findings provide further support for the BASDA as an efficient
      measure of drinking in an individual's social network. Methodological
      considerations as well as recommendations for future investigations in this area
      are discussed.

PMID- 23948543
TI  - Methoxetamine misuse and toxicity.

PMID- 23948544
TI  - Editor's perspectives--ASiT abstracts.

PMID- 23948545
TI  - Mechanism of rapid elimination of lysophosphatidic acid and related lipids from
      the circulation of mice.
AB  - Lysophosphatidic acid (LPA) is a bioactive lipid mediator. Concentrations of the
      major LPA species in mouse plasma decreased uniformly following administration of
      a potent selective inhibitor of the LPA-generating lysophospholipase D autotaxin,
      identifying an active mechanism for removal of LPA from the circulation. LPA,
      akylglycerol phosphate (AGP), sphingosine 1-phosphate (S1P), and a variety of
      structural mimetics of these lipids, including phosphatase-resistant phosphonate
      analogs of LPA, were rapidly eliminated (t1/2 < 30 s) from the circulation of
      mice following intravenous administration of a single bolus dose without
      significant metabolism in situ in the blood. These lipids accumulated in the
      liver. Elimination of intravenously administered LPA was blunted by ligation of
      the hepatic circulation, and ~90% of LPA administered through the portal vein was
      accumulated by the isolated perfused mouse liver at first pass. At early times
      following intravenous administration, more LPA was associated with a
      nonparenchymal liver cell fraction than with hepatocytes. Primary cultures of
      nonparenchymal liver cells rapidly assimilated exogenously provided LPA. Our
      results identify hepatic uptake as an important determinant of the
      bioavailability of LPA and bioactive lysophospholipid mimetics and suggest a
      mechanism to explain changes in circulating LPA levels that have been associated
      with liver dysfunction in humans. 

PMID- 23948547
TI  - Mycobacterium tuberculosis rrs A1401G mutation correlates with high-level
      resistance to kanamycin, amikacin, and capreomycin in clinical isolates from
      mainland China.
AB  - Mutations correlating phenotypic resistance level with the injectable second-line
      anti-tuberculosis drugs (SLDs) including kanamycin (KAN), amikacin (AMK), and
      capreomycin (CAP) remain elusive. A collection of 114 Mycobacterium tuberculosis
      clinical isolates from mainland China was analyzed. The minimum inhibitory
      concentration (MIC) of each strain was determined and the sequences of rrs, tlyA,
      promoter of eis as well as 5' untranslated region (UTR) of whiB7 were amplified
      and sequenced. No mutation in tlyA, promoter of eis and 5' UTR of whiB7, was
      found to be associated with resistance among these samples. Sequencing data of
      1400 rrs region demonstrated the A1401G mutation in rrs was prevalent, which
      presented in 84% of the KAN resistant isolates while only in about 50% of the AMK
      or CAP resistant isolates. Furthermore, most of the resistant isolates with
      A1401G mutation showed high-level resistance to these injectable SLDs. In
      conclusion, our results suggest the rrs A1401G mutation was related to high-level
      resistance to KAN, AMK, and CAP in M. tuberculosis isolates from mainland China. 

PMID- 23948548
TI  - Multiplex detection of antibiotic resistance genes using padlock probes.
AB  - The elucidation of resistance mechanisms is of central importance to providing
      and maintaining efficient medical treatment. However, molecular detection methods
      covering the complete set of resistance genes with a single test are still
      missing. Here, we present a novel 100-plex assay based on padlock probes in
      combination with a microarray that allows the simultaneous large-scale
      identification of highly diverse beta-lactamases. The specificity of the assay
      was performed using 70 clinical bacterial isolates, recovering 98% of the beta
      lactamase nucleotide sequences present. Additionally, the sensitivity was
      evaluated with PCR products and genomic bacterial DNA, revealing a detection
      limit of 10(4) DNA copies per reaction when using PCR products as the template.
      Pre-amplification of genomic DNA in a 25-multiplex PCR further facilitated the
      detection of beta-lactamase genes in dilutions of 10(7) cells/mL. In summary, we
      present an efficient, highly specific, and highly sensitive multiplex detection
      method for any gene. 

PMID- 23948546
TI  - Niacin, an old drug with a new twist.
AB  - Niacin (nicotinic acid) has been used for decades as a lipid-lowering drug. The
      clinical use of niacin to treat dyslipidemic conditions is limited by its side
      effects. Niacin, along with fibrates, are the only approved drugs which elevate
      high density lipoprotein cholesterol (HDLc) along with its effects on low density
      lipoprotein cholesterol (LDLc) and triglycerides. Whether niacin has a beneficial
      role in lowering cardiovascular risk on the background of well-controlled LDLc
      has not been established. In fact, it remains unclear whether niacin, either in
      the setting of well-controlled LDLc or in combination with other lipid-lowering
      agents, confers any therapeutic benefit and if so, by which mechanism. The
      results of recent trials reject the hypothesis that simply raising HDLc is
      cardioprotective. However, in the case of the clinical trials, structural
      limitations of trial design complicate their interpretation. This is also true of
      the most recent Heart Protection Study 2-Treatment of HDLc to Reduce the
      Incidence of Vascular Events (HPS2-THRIVE) trial in which niacin is combined with
      an antagonist of the D prostanoid (DP) receptor. Human genetic studies have also
      questioned the relationship between cardiovascular benefit and HDLc. It remains
      to be determined whether niacin may have clinical utility in particular
      subgroups, such as statin intolerant patients with hypercholesterolemia or those
      who cannot achieve a sufficient reduction in LDLc. It also is unclear whether a
      potentially beneficial effect of niacin is confounded by DP antagonism in HPS2
      THRIVE. 

PMID- 23948549
TI  - Up-regulation of pro-angiogenic factors and establishment of tolerance in
      malignant pleural effusions.
AB  - INTRODUCTION: Malignant pleural effusions (MPEs) are a significant source of
      cancer morbidity and mortality. Currently there is no cure for MPEs and
      treatments only palliate the symptoms. The purpose of this study was to determine
      if there are differences in markers of angiogenesis and immune phenotypes between
      adenocarcinoma-induced MPEs and benign pleural effusions (BPEs). METHODS: Pleural
      effusions were collected from patients with MPEs and BPEs. Cells were isolated
      from effusions and characterized using fluorescent cell sorting (FACS). Pleural
      effusions were evaluated by ELISA for VEGF-A. An angiogenesis protein array was
      completed to compare protein expression in malignant and non-malignant effusions.
      RESULTS: FACS analysis demonstrated lower accumulation of cytotoxic T-cells and
      significantly higher accumulation of monocytes, dendritic cells, mesothelial and
      tumor cells in MPEs compared to benign pleural effusions. MPEs were found to have
      77-fold higher VEGF-A levels compared to BPEs. The angiogenesis protein array
      demonstrated elevated levels of pro-angiogenic factors VEGF-A, CXCL4 and MMP-8,
      and low levels of pro-inflammatory cytokines IL-8, MCP-1, and TGF-beta1 in MPEs.
      CONCLUSIONS: MPE is biased toward a Th2 dominant state. There is an increase in
      expression of VEGF-A and other pro-angiogenic factors in MPE. These data suggest
      there is a role for anti-angiogenesis therapy in patients with MPEs.

PMID- 23948550
TI  - microRNAs are important players in head and neck carcinoma: a review.
AB  - The results of treatment of head and neck tumors remain poor for decades. It
      means that after surgery, chemotherapy is not a proper choice, as tumors of this
      region are relatively resistant to cytotoxic drugs. A little progress was noted
      only for radiotherapy outcome. Consequently, clinicians and researchers'
      expectations are focused on targeted therapy, where microRNAs (miRNAs, miRs) seem
      to be the most promising target. After the year 2000, miRNAs became new players
      on the scene of cancer science. Since then, extensive investigations have been
      performed with a hope of finding a new prognostic and diagnostic tool and
      bridging them with a bright new way of understanding the basis of molecular
      carcinogenesis. miRNAs display astonishing specificity and thus are associated
      with pathoclinical parameters of the disease. After more than a decade of ongoing
      studies, in this review we attempt to summarize the current knowledge of miRNAs
      in malignancies arising in head and neck sites and with a majority of squamous
      cells of the epithelium.

PMID- 23948551
TI  - RRSM with a data-dependent threshold for miRNA target prediction.
AB  - Predicting miRNA target genes is one of the important issues in bioinformatics.
      The correlation analysis is a widely used method for exploring miRNA targets
      through microarray data. However, the experimental results show that correlation
      analysis leads to large false positive or negative results. In addition, the
      correlation analysis is not appropriate when multiple miRNAs simultaneously
      regulate a gene. Recently, the relative R squared method (RRSM) has been proposed
      for miRNA target prediction, which is shown to be superior to some existing
      methods. To adopt the RRSM, we need first to set thresholds to select a
      proportion of potential targets. In the previous studies, the threshold is set to
      be fixed, which does not depend on the characteristic of a gene. Due to the
      diversity of the functions of genes, a data-dependent threshold may be more
      feasible in real data applications than a data-independent threshold. In this
      study, we propose a threshold selection method which is based on the distribution
      of the relative R squared statistic. The proposed method is shown to
      significantly improve the previous prediction results by selecting more
      experimentally validated targets. 

PMID- 23948552
TI  - Abrupt community transitions and cyclic evolutionary dynamics in complex food
      webs.
AB  - Understanding the emergence and maintenance of biodiversity ranks among the most
      fundamental challenges in evolutionary ecology. While processes of community
      assembly have frequently been analyzed from an ecological perspective, their
      evolutionary dimensions have so far received less attention. To elucidate the eco
      evolutionary processes underlying the long-term build-up and potential collapse
      of community diversity, here we develop and examine an individual-based model
      describing coevolutionary dynamics driven by trophic interactions and
      interference competition, of a pair of quantitative traits determining predator
      and prey niches. Our results demonstrate the (1) emergence of communities with
      multiple trophic levels, shown here for the first time for stochastic models with
      linear functional responses, and (2) intermittent and cyclic evolutionary
      transitions between two alternative community states. In particular, our results
      indicate that the interplay of ecological and evolutionary dynamics often results
      in extinction cascades that remove the entire trophic level of consumers from a
      community. Finally, we show the (3) robustness of our results under variations of
      model assumptions, underscoring that processes of consumer collapse and
      subsequent rebound could be important elements of understanding biodiversity
      dynamics in natural communities. 

PMID- 23948553
TI  - Pattern identification and characterization reveal permutations of organs as a
      key genetically controlled property of post-meristematic phyllotaxis.
AB  - In vascular plants, the arrangement of organs around the stem generates geometric
      patterns called phyllotaxis. In the model plant, Arabidopsis thaliana, as in the
      majority of species, single organs are initiated successively at a divergence
      angle from the previous organ close to the canonical angle of 137.5 degrees ,
      producing a Fibonacci spiral. Given that little is known about the robustness of
      these geometric arrangements, we undertook to characterize phyllotaxis by
      measuring divergence angles between organs along the stems of wild-type and
      specific mutant plants with obvious defects in phyllotaxis. Sequences of measured
      divergence angles exhibit segments of non-canonical angles in both genotypes,
      albeit to a far greater extent in the mutant. We thus designed a pipeline of
      methods for analyzing these perturbations. The latent structure models used in
      this pipeline combine a non-observable model representing perturbation patterns
      (either a variable-order Markov chain or a combinatorial model) with von Mises
      distributions representing divergence angle uncertainty. We show that the
      segments of non-canonical angles in both wild-type and mutant plants can be
      explained by permutations in the order of insertion along the stem of two or
      three consecutive organs. The number of successive organs between two
      permutations reveals specific patterns that depend on the nature of the preceding
      permutation (2- or 3-permutation). We also highlight significant individual
      deviations from 137.5 degrees  in the level of baseline segments and a marked
      relationship between permutation of organs and defects in the elongation of the
      internodes between these organs. These results demonstrate that permutations are
      an intrinsic property of spiral phyllotaxis and that their occurrence is
      genetically regulated. 

PMID- 23948554
TI  - 'Project launch': from research finding to therapeutic product.
AB  - Only 0.1-0.5% of new therapy candidates gains marketing approval; just 10-20% of
      the approved ones ultimately recoup the ~0.6-0.9$USbn invested into their R&D
      until marketing authorisation. One reason is the high inherent risk of new
      therapeutic products development. Further reasons are suboptimal decisions during
      R&D and, too often, lack of adequate experience. To bridge the latter gap, this
      article succinctly reviews identification of new product opportunities and their
      patent protection, the resulting commercial opportunity and portfolio valuation,
      planning and conduct of the ensuing preclinical and clinical tests, as well as
      therapeutic product registration and price reimbursement, covering risk
      management as an aside. The article also clarifies the key terms, identifies the
      main pit falls, highlights the essential requirements for and the goals of
      different product development steps, to facilitate communication between
      researchers and developers. By combining public information with personal
      experience and recommendations the article aims at informing more broadly those
      who are familiar mainly with some of the (strictly regulated) activities involved
      in design, development and launch of new therapeutic products, be it that they
      are medicinal products or medical devices. Taken together, this should support
      initiation and evolution of new therapeutic products and assist researchers in
      finding-and better and more smoothly co-operating with-consultants or partners in
      development and marketing.

PMID- 23948555
TI  - Modelling skin permeability with micellar liquid chromatography.
AB  - This study evaluates the potential application of micellar liquid chromatography
      (MLC) to predict skin permeation with a series of model compounds. MLC has
      previously been found to be useful in the prediction of partition coefficient
      values (logP) for pharmaceutical compounds, yet has not been incorporated in skin
      permeability models prior to this work. This article provides statistically
      supported data that this technique enhances the ability to predict the
      permeability of similar drugs through the skin (K(p)). The replacement of a
      traditional physicochemical parameter, namely the octanol-water partition
      coefficient (logP(ow)) with a chromatographically determined value (logP(mw)),
      results in a quantitative partition-permeability relationship that is robust to
      variation. MLC offers many benefits compared with the traditional techniques
      employed to obtain logP values.

PMID- 23948556
TI  - Cancer Letters. Featuring the guest editors: Wael M. ElShamy and Roy J. Duhe.

PMID- 23948557
TI  - Inhibition of novel reassortant avian influenza H7N9 virus infection in vitro
      with three antiviral drugs, oseltamivir, peramivir and favipiravir.
AB  - BACKGROUND: A novel reassortant avian-origin influenza A (H7N9) virus was
      isolated from respiratory specimens obtained from three patients and was
      identified as H7N9 in China. Antiviral agents are required to treat patients with
      avian influenza H7N9 virus infection. METHODS: In this study, we assessed the
      antiviral potential of oseltamivir, peramivir, favipiravir (T-705), amantadine
      and rimantadine against novel reassortant avian-origin influenza H7N9 virus in
      vitro. RESULTS: All three avian influenza H7N9 virus strains were sensitive to
      oseltamivir, peramivir and favipiravir (T-705), but resistant to amantadine and
      rimantadine. CONCLUSIONS: Our data show a pattern of antiviral sensitivity for
      this novel H7N9 strain of influenza that suggests the compounds oseltamivir,
      peramivir and favipiravir should be useful for therapy.

PMID- 23948558
TI  - In vitro effect of heather extracts on Trichostrongylus colubriformis eggs,
      larvae and adults.
AB  - This study was carried out to evaluate the in vitro effects of different heather
      species on Trichostrongylus colubriformis eggs, larvae and adult worms, and
      obtain scientific evidence to attribute these effects to the action of their
      phenolic compounds and/or tannins. Total phenolic extracts of three heather
      species (Calluna vulgaris, Erica cinerea, and Erica umbellata) and an equal
      mixture of these three extracts were tested in vitro in the three development
      stages of T. colubriformis using an egg hatching assay (EHA), larval exsheathment
      inhibition assay (LEIA), and adult motility inhibition assay (AMIA). The egg
      hatching rate was measured after incubation with heather extracts for 48 h at 25
      degrees C. Infective third-stage larvae (L3) were incubated for 3h at 25 degrees
      C with heather extracts. The evolution of artificial exsheathment over time was
      measured with repeated observations at 20-min intervals for 60 min. Adult worms
      were obtained from one donor goat and incubated with the extracts at 37 degrees C
      for 5 days in 48-multiwell plates. Worm motility was measured at 0, 19, 24, 43,
      48, 67, 72, 96 and 115 h after the beginning of the experiment. The extracts were
      tested at concentrations of 75, 150, 300, 600 and 1,200 MUg/ml. All extracts
      significantly (P<0.001) inhibited egg hatching and the effect was dose dependent.
      All extracts inhibited or delayed the exsheathment of T. colubriformis L3, and
      the effect was dose dependent for C. vulgaris. Incubation with heather extracts
      induced a reduction in adult worm motility compared to control, although
      significant (P<0.05) differences were only found at the highest concentrations.
      Additional studies showed that purified tannins of the same heather species
      disturbed T. colubriformis larval exsheathment. All these results confirm the
      anthelmintic properties of heather against T. colubriformis, and suggest that not
      only tannins but also some other phenolic compounds might be involved.

PMID- 23948559
TI  - In vitro and in vivo evaluation of cypermethrin, amitraz, and piperonyl butoxide
      mixtures for the control of resistant Rhipicephalus (Boophilus) microplus (Acari:
      Ixodidae) in the Mexican tropics.
AB  - A study was conducted to evaluate the efficacy of cypermethrin, amitraz, and
      piperonyl butoxide (PBO) mixtures, through in vitro laboratory bioassays and in
      vivo on-animal efficacy trials, for the control of resistant Rhipicephalus
      (Boophilus) microplus on cattle in the Mexican tropics. Also, to examine
      mechanisms of resistance to cypermethrin in this tick population, the frequency
      of a mutated sodium channel gene (F1550I) was determined using a PCR assay.
      Results of laboratory bioassays using modified larval packet tests revealed that
      cypermethrin toxicity was synergized by PBO (from 46.6-57.0% to 83.7-85.0% larval
      mortality; P<0.05). The cypermethrin and amitraz mixture showed an additive
      effect (from 46.6-57.0% to 56.0-74.3% larval mortality). Strong synergism was
      observed with the mixture of cypermethrin+amitraz+PBO and this mixture was the
      most effective killing resistant tick larvae in vitro (96.7-100% of larval
      mortality). Tick larvae surviving exposure to cypermethrin or mixtures either
      with amitraz and PBO in vitro showed 2.9-49.6 higher probability to present the
      mutated allele than those killed by acaricide treatment (P<0.05). In the in vivo
      trial, the mixtures containing cypermethrin+PBO (80.6-97.3%), and
      cypermethrin+amitraz (87.0-89.7%) were more efficacious than cypermethrin alone
      (76.3-80.5%). The highest level of efficacy was obtained with the mixture of
      cypermethrin+amitraz+PBO, which yielded >95% control that persisted for 28 days
      post-treatment against R. microplus infesting cattle when tested under field
      conditions in the Mexican tropics. Although this mixture is a potentially useful
      tool to combat pyrethroid resistance, a product based on an acaricide mixture
      like the one tested in this study has to be used rationally. 

PMID- 23948560
TI  - Nitrogen and water recovery from animal slurries by a new integrated
      ultrafiltration, reverse osmosis and cold stripping process: a case study.
AB  - The correct management of livestock manure represents one of the major challenge
      for the agricultural sector development, as it may ensure environmental and
      economic sustainability of livestock farming. In this work, a new treatment
      process called N-Free((r)), was monitored on two plants treating digested cattle
      manure (DCM) and digested swine manure (DSM). The process is characterized by
      sequential integration of solid/liquid separations, ultrafiltration, reverse
      osmosis and cold ammonia stripping. Solid and liquid streams were characterized
      regarding TS, TKN, N-NH4(+), P and K content allowing to draw a complete mass
      balance. The main results were a substantial reduction of initial digestate
      volume (38 and 51% in DCM and DSM respectively) as clean water and a high N
      NH4(+) removal percentage (47 and 71% in DCM and DSM respectively), through cold
      ammonia stripping, allowing the production of up to 1.8 m(3) concentrated
      ammonium sulfate, every 100 m(3) of treated digestate. The concentrated streams,
      rich in either organic or mineral N, P and K, can be efficiently used for land
      application. The N-Free((r)) technology demonstrated to be a valuable candidate
      for the path toward nutrient and water recycle, in a new sustainable agriculture
      and farming concept.

PMID- 23948561
TI  - Mechanistic and statistical models of total Vibrio abundance in the Neuse River
      Estuary.
AB  - Bacteria in the genus Vibrio are ubiquitous to estuarine waters worldwide and are
      often the dominant genus recovered from these environments. This genus contains
      several potentially pathogenic species, including Vibrio vulnificus, Vibrio
      cholerae, Vibrio parahaemolyticus, and Vibrio alginolyticus. These bacteria have
      short generation times, as low as 20-30 min, and can thus respond rapidly to
      changing environmental conditions. A five-parameter mechanistic model was
      generated based on environmental processes including hydrodynamics, growth, and
      death rates of Vibrio bacteria to predict total Vibrio abundance in the Neuse
      River Estuary of eastern North Carolina. Additionally an improved statistical
      model was developed using the easily monitored parameters of temperature and
      salinity. This updated model includes data that covers more than eight years of
      constant bacterial monitoring, and incorporates extreme weather events such as
      droughts, storms, and floods. These models can be used to identify days in which
      bacterial abundance might coincide with increased health risks.

PMID- 23948562
TI  - Optimized aeration strategies for nitrogen and phosphorus removal with aerobic
      granular sludge.
AB  - Biological wastewater treatment by aerobic granular sludge biofilms offers the
      possibility to combine carbon (COD), nitrogen (N) and phosphorus (P) removal in a
      single reactor. Since denitrification can be affected by suboptimal dissolved
      oxygen concentrations (DO) and limited availability of COD, different aeration
      strategies and COD loads were tested to improve N- and P-removal in granular
      sludge systems. Aeration strategies promoting alternating nitrification and
      denitrification (AND) were studied to improve reactor efficiencies in comparison
      with more classical simultaneous nitrification-denitrification (SND) strategies.
      With nutrient loading rates of 1.6 gCOD L(-1) d(-1), 0.2 gN L(-1) d(-1), and 0.08
      gP L(-1) d(-1), and SND aeration strategies, N-removal was limited to 62.3 +/-
      3.4%. Higher COD loads markedly improved N-removal showing that denitrification
      was limited by COD. AND strategies were more efficient than SND strategies.
      Alternating high and low DO phases during the aeration phase increased N-removal
      to 71.2 +/- 5.6% with a COD loading rate of 1.6 gCOD L(-1) d(-1). Periods of low
      DO were presumably favorable to denitrifying P-removal saving COD necessary for
      heterotrophic N-removal. Intermittent aeration with anoxic periods without mixing
      between the aeration pulses was even more favorable to N-removal, resulting in
      78.3 +/- 2.9% N-removal with the lowest COD loading rate tested. P-removal was
      under all tested conditions between 88 and 98%, and was negatively correlated
      with the concentration of nitrite and nitrate in the effluent (r = -0.74, p <
      0.01). With low COD loading rates, important emissions of undesired N2O gas were
      observed and a total of 7-9% of N left the reactor as N2O. However, N2O emissions
      significantly decreased with higher COD loads under AND conditions.

PMID- 23948563
TI  - Controllability analysis as a pre-selection method for sensor placement in water
      distribution systems.
AB  - Detection of contamination events in water distribution systems is a crucial task
      for maintaining water security. Online monitoring is considered as the most cost
      effective technology to protect against the impacts of contaminant intrusions.
      Optimization methods for sensor placement enable automated sensor layout design
      based on hydraulic and water quality simulation. However, this approach results
      in an excessive computational burden. In this paper we outline the application of
      controllability analysis as preprocessing method for sensor placement. Based on
      case studies we demonstrate that the method decreases the number of decision
      variables for subsequent optimization dramatically to app. 30 to 40 percent. 

PMID- 23948564
TI  - Experimental spectroscopic (FTIR, FT-Raman, FT-NMR, UV-Visible) and DFT studies
      of 1-ethyl-1,4-dihydro-7-methyl-4oxo-1,8 napthyridine-3-carboxylic acids.
AB  - The solid phase FTIR and FT-Raman spectra of 1-ethyl-1,4-dihydro-7-methyl-4oxo
      1,8 napthyridine-3-carboxylic acid (EDMONCA) have been recorded in the regions
      4000-500 and 4000-400 cm(-1) respectively. The equilibrium geometry, harmonic
      vibrational frequencies have been investigated by DFT/B3LYP and B3PW91 methods
      with 6-311G (d,p) basis set. The different between the observed and scaled wave
      number values of most of the fundamental is very small. The assignments of the
      vibrational spectra have been carried out with the aid of normal coordinate
      analysis (NCA) following the scaled quantum mechanical force field methodology
      (SQMFFM). Stability of the molecule arising from hyper conjugative interactions,
      charge delocalization has been analyzed using natural bond orbital (NBO)
      analysis. UV-Visible spectrum of the compound was recorded and the electronic
      properties HOMO and LOMO energies were measured. The electric dipole moment (MUD)
      and first hyperpolarizability (betatot) values of the investigated molecule were
      computed using ab initio quantum mechanical calculations. The calculated results
      also show that the EDMONCA molecule may have microscopic nonlinear optics (NLO)
      behavior with non-zero values. (1)H and (13)C NMR spectra were recorded and (1)H
      and (13)C nuclear magnetic resonance chemical shift of the molecule were
      calculated using the gauge independent atomic orbital (GIAO) method. Thermal
      stability of EDMONCA was studied by thermogravimetric analysis (TGA). Next Fukui
      function was calculated to explain the chemical selectivity or reactivity site in
      EDMONCA. Finally molecular electrostatic potential (MEP) and other molecular
      properties were performed.

PMID- 23948565
TI  - Spectroscopic investigations on the orientation of 1,4-dibromonaphthalene on
      silver nanoparticles.
AB  - Silver nanoparticles (Ag NPs) have been prepared by solution combustion method
      with glycine as fuel. Silver nanoparticles were characterized by X-Ray
      Diffraction (XRD), High Resolution Transmission Electron Microscopy (HRTEM) and
      UV-visible spectroscopy. The prepared silver nanoparticles exhibit cubic
      crystalline structure with grain size of 59 nm. HRTEM image shows that the silver
      nanoparticles have strain and four-fold symmetry formed by twinning in the
      crystal structure. The optical adsorption spectrum shows that the surface plasmon
      resonance peak of silver is observed at 380 nm. The orientation of 1,4
      dibromonaphthlaene (1,4-DBrN) on silver nanoparticles has been inferred from nRs
      and SERS spectral features. The absence of a C-H stretching vibrations, the
      observed high intense C-H out-of-plane bending modes and high intense C-Br
      stretching vibration suggest that the 1,4-DBrN molecule may be adsorbed in a
      'stand-on' orientation to the surface.

PMID- 23948566
TI  - Elucidation of potentially virulent factors of Candida albicans during serum
      adaptation by using quantitative time-course proteomics.
AB  - Candida albicans is an opportunistic pathogen that causes fatal disease if the
      host immunity is compromised. The mortality rate of systemic candidiasis is very
      high; hence, there is a ceaseless demand for novel pharmaceuticals. In this
      study, quantitative time-course proteomics of C. albicans during adaptation to
      fetal bovine serum (FBS) is described. Survival in blood is essential for
      virulence of C. albicans, and a detailed analysis is required. We cultivated C.
      albicans in FBS for 0-180min, and determined quantitative time-course variations
      of 1024 proteins in the cultured cells by using a LC-MS/MS system with a long
      monolithic silica capillary column. Clustering analysis identified FBS-induced
      proteins associated with detoxification of oxidative species, high-affinity
      glucose transport, citrate cycle, oxidative phosphorylation, and iron
      acquisition. Furthermore, we identified possible virulence factors such as
      orf19.4914.1 (named Blood-induced peptide 1, Blp1). Heterologous expression of
      BLP1 in Saccharomyces cerevisiae shortened the lag phase and resulted in a
      pleiotropic stress-tolerance phenotype, indicating a possible role for quick
      adaptation to a stressful environment. While further experiments are necessary to
      prove virulence of the identified factors, systematic identification of candidate
      virulence proteins in this study will lead to profound understanding of virulence
      of C. albicans. BIOLOGICAL SIGNIFICANCE: This paper describes time-course
      proteomics of C. albicans during adaptation to serum, which is an essential
      process for fatal systemic candidiasis. Using a LC-MS/MS system with a monolithic
      silica capillary column, we have successfully characterized time-course
      variations of 1024 proteins. Among them, orf19.4914.1 (Blp1) was identified as a
      novel pleiotropic stress-tolerance peptide, which could have an important role
      for virulence of C. albicans.

PMID- 23948567
TI  - Cloning of three 2,3-dihydroxybiphenyl-1,2-dioxygenase genes from Achromobacter
      sp. BP3 and the analysis of their roles in the biodegradation of biphenyl.
AB  - Three 2,3-dihydroxybiphenyl 1,2-dioxygenase genes (designated as bphC1, bphC2 and
      bphC3) were cloned from a biphenyl-degrading strain Achromobacter sp. BP3. The
      amino acid sequence of BphC1 and BphC3 had high similarity (>99%) with the
      reported BphCs, while BphC2 showed relatively low identity (29.51-50.17%) with
      the reported BphCs, which indicated that bphC2 might be a novel gene. The bphC1,
      bphC2 and bphC3 genes were expressed in Escherichia coli BL21 and the products
      were homogenously purified. BphC1, BphC2 and BphC3 displayed maximum activity at
      30 degrees C, 30 degrees C and 40 degrees C, respectively. Their optimal
      catalysis pH was 8.0, 9.0 and 9.0, respectively. BphC1 and BphC2 had higher
      substrate affinity and catalytic efficiency on 2,3-dihydroxybiphenyl, while BphC3
      exhibited these features on aromatic monocyclic substrates. The bphC1 gene was
      only induced by biphenyl and bphC3 was induced by both biphenyl and toluene,
      while bphC2 was constitutively expressed in strain BP3. These results suggested
      that BphC1 and BphC3 played a role in the upstream and downstream metabolic
      pathways of biphenyl, respectively. However, BphC2 might play a supplementary
      role and contribute more to the upstream than to the downstream pathway.

PMID- 23948568
TI  - Structure and properties of G84R and L99M mutants of human small heat shock
      protein HspB1 correlating with motor neuropathy.
AB  - Some properties of G84R and L99M mutants of HspB1 associated with peripheral
      distal neuropathies were investigated. Homooligomers formed by these mutants are
      larger than those of the wild type HspB1. Large oligomers of G84R and L99M
      mutants have compromised stability and tend to dissociate at low protein
      concentration. G84R and L99M mutations promote phosphorylation-dependent
      dissociation of HspB1 oligomers without affecting kinetics of HspB1
      phosphorylation by MAPKAP2 kinase. Both mutants weakly interact with HspB6
      forming small heterooligomers and being unable to form large heterooligomers
      characteristic for the wild type HspB1. G84R and L99M mutants possess lower
      chaperone-like activity than the wild type HspB1 with several model substrates.
      We suggest that G84R mutation affects mobility and accessibility of the N
      terminal domain thus modifying interdimer contacts in HspB1 oligomers. The L99M
      mutation is located within the hydrophobic core of the alpha-crystallin domain
      close to the key R140 residue, and could affect the dimer stability.

PMID- 23948569
TI  - The inhibitory effects of Escherichia coli maltose binding protein on beta
      amyloid aggregation and cytotoxicity.
AB  - The aggregation of beta-amyloid (Abeta) peptide from its monomeric to its
      fibrillar form importantly contributes to the development of Alzheimer's disease.
      Here, we investigated the effects of Escherichia coli maltose binding protein
      (MBP), which has been previously used as a fusion protein, on Abeta42
      fibrillization, in order to improve understanding of the self-assembly process
      and the cytotoxic mechanism of Abeta42. MBP, at a sub-stoichiometric ratio with
      respect to Abeta42, was found to have chaperone-like inhibitory effects on beta
      sheet fibril formation, due to the accumulation of Abeta42 aggregates by
      sequestration of active Abeta42 species as Abeta42-MBP complexes. Furthermore,
      MBP increased the lag time of Abeta42 polymerization, decreased the growth rate
      of fibril extension, and suppressed Abeta42 mediated toxicity in human
      neuroblastoma SH-SY5Y cells. It appears that MBP decreases the active
      concentration of Abeta42 by sequestering it as Abeta42-MBP complex, and that this
      sequestration suppresses ongoing nucleation and retards the growth rate of
      Abeta42 species required for fibril formation. We speculate that inhibition of
      the growth rate of potent Abeta42 species by MBP suppresses Abeta42-mediated
      toxicity in SH-SY5Y cells.

PMID- 23948570
TI  - Remodeling of liver phospholipidomic profile in streptozotocin-induced diabetic
      rats.
AB  - Lipid homeostasis in liver is known to be altered with diabetes mellitus,
      ultimately leading to liver damage and related complications. The present work
      aimed to evaluate changes in the liver phospholipid profile after 4 months of
      uncontrolled hyperglycemia. Twenty Wistar rats were divided into two groups:
      control and streptozotocin-treated (T1DM). After 4 months, animals were
      sacrificed and morphological characterization of liver was performed and related
      with serum markers of hepatic damage. Lipid extracts were obtained from liver and
      phospholipid (PL) classes were quantified. Lipid molecular species were
      determined by LC-MS and LC-MS/MS, and fatty acids by GC-MS. Concomitantly with
      signs of hepatic damage we found variations in the relative amount of
      phospholipid classes in T1DM, characterized by a decrease in PLs with choline
      head group, and by an increase in the relative content of other PL classes. A
      remodeling in PL fatty acyl chains was observed in T1DM liver, with a similar
      pattern to all the PL classes, and consisting in the reduction of 16:0 and an
      increase of 18:0 and 18:2 acyl chains. The observed changes in T1DM lipid profile
      may contribute to the altered membrane properties underlying hepatic damage,
      worsening the metabolic alterations that characterize T1DM.

PMID- 23948571
TI  - Managing end stage lung disease in children.
AB  - Over the course of a career most physicians will manage only a handful of
      children through End Stage Lung Disease. Nonetheless, the approach of the
      physician to this challenge will have a profound impact on the children and
      families they encounter. Managing the end of life well can bring personal growth
      and professional satisfaction. In this review we highlight aspects of the
      Palliative Care approach and its integration with restorative and life-prolonging
      care. We review the role of active treatment, respiratory support, symptom
      management and psychosocial aspects of the management of End Stage Lung Disease. 

PMID- 23948572
TI  - Correlates of protection against influenza infection in humans--on the path to a
      universal vaccine?
AB  - Influenza is an acute respiratory viral infection with high mutation rate and
      pandemic potential. Vaccination is an effective means of prevention and control
      of influenza, but the challenges of vaccine mismatches for the next influenza
      seasons and adequate global supply of influenza vaccines limit its effectiveness.
      Protective immunity in vaccination or natural infection is primarily mediated by
      antibody responses against surface proteins of influenza including haemagglutinin
      (HA) as the major neutralizing target, whereas strong T cell responses to
      internal viral proteins are associated with reduced disease severity. Recently,
      identification of broadly neutralizing antibodies against the conserved stem
      region of HA from influenza infected individuals has invigorated interest in
      development of a universal vaccine against different subtypes of influenza.
      Moreover, because of the cross-reactive nature of T cell recognition and more
      conserved internal antigens of influenza, strategies that boost memory T cell
      responses to these internal antigens may provide not only help for antibody
      mediated protection but also limit the cell damage caused by viral infection
      directly. This is particularly important in acute infection with new pandemic
      viruses or antibody-escape variants where there are no pre-existing neutralizing
      antibodies. Here, we review the protective immune correlates against human
      influenza infection and discuss current status of universal influenza vaccine
      development. 

PMID- 23948573
TI  - Purposive facebook recruitment endows cost-effective nutrition education program
      evaluation.
AB  - BACKGROUND: Recent legislation established a requirement for nutrition education
      in federal assistance programs to be evidence-based. Recruitment of low-income
      persons to participate and evaluate nutrition education activities can be
      challenging and costly. Facebook has been shown to be a cost-effective strategy
      to recruit this target audience to a nutrition program. OBJECTIVE: The purpose of
      our study was to examine Facebook as a strategy to recruit participants,
      especially Supplemental Nutrition Assistance Program Education (SNAP-Ed) eligible
      persons, to view and evaluate an online nutrition education program intended to
      be offered as having some evidence base for SNAP-Ed programming. METHODS: English
      speaking, low-income Pennsylvania residents, 18-55 years with key profile words
      (eg, Supplemental Nutrition Assistance Program, Food bank), responded to a
      Facebook ad inviting participation in either Eating Together as a Family is Worth
      It (WI) or Everyone Needs Folic Acid (FA). Participants completed an online
      survey on food-related behaviors, viewed a nutrition education program, and
      completed a program evaluation. Facebook set-up functions considered were costing
      action, daily spending cap, and population reach. RESULTS: Respondents for both
      WI and FA evaluations were similar; the majority were white, <40 years,
      overweight or obese body mass index, and not eating competent. A total of 807
      Facebook users clicked on the WI ad with 73 unique site visitors and 47 of them
      completing the program evaluation (ie, 47/807, 5.8% of clickers and 47/73, 64% of
      site visitors completed the evaluation). Cost per completed evaluation was US
      $25.48; cost per low-income completer was US $39.92. Results were similar for the
      FA evaluation; 795 Facebook users clicked on the ad with 110 unique site
      visitors, and 73 completing the evaluation (ie, 73/795, 9.2% of ad clickers and
      73/110, 66% of site visitors completed the evaluation). Cost per valid completed
      survey with program evaluation was US $18.88; cost per low-income completer was
      US $27.53. CONCLUSIONS: With Facebook we successfully recruited low-income
      Pennsylvanians to online nutrition program evaluations. Benefits using Facebook
      as a recruitment strategy included real-time recruitment management with lower
      costs and more efficiency compared to previous data from traditional research
      recruitment strategies reported in the literature. Limitations prompted by
      repeated survey attempts need to be addressed to optimize this recruitment
      strategy.

PMID- 23948574
TI  - Lithium usage and renal function testing in a large UK community population; a
      case-control study.
AB  - OBJECTIVE: This study investigates the prevalence of lithium use, monitoring
      practice and associated effects on renal function in a large UK community sample.
      METHOD: A large population-based renal function database was cross-referenced
      with a general practitioner database of 404,673 patients. The renal function of
      patients prescribed lithium during the 2-year period was compared with that of
      matched controls. The renal monitoring patterns of these cases were investigated
      in a naturalistic observational study. Data underwent parametric testing -
      continuous variables by analysis of variance, with appropriate adjustment, and
      categorical outcomes by chi(2) testing. Block analysis of variance was undertaken
      on case-control data. RESULTS: A total of 422 patients in the database were
      prescribed lithium. Renal function monitoring in accordance with published
      guidelines occurred in 69% of patients. Patients taking lithium had a
      significantly higher serum creatinine (5.8 MUmol/L, P<.001) and lower glomerular
      filtration rate (5.9 ml/min, P<.001) when compared to matched controls.
      CONCLUSIONS: This is the first study carried out in a large community sample.
      Lithium remains widely prescribed in the community setting. The study confirms
      that lithium has a statistically and clinically significant negative effect on
      renal function. Despite published guidelines and recognition of the importance of
      serial measurements, monitoring of renal function is inconsistent.

PMID- 23948575
TI  - The relation between Internet and social media use and the demographic and
      clinical parameters, quality of life, depression, cognitive function and sleep
      quality in hemodialysis patients: social media and hemodialysis.
AB  - OBJECTIVE: There are very few studies in the literature investigating the
      Internet use in hemodialysis (HD) patients. However, no study examined the
      relationship between Internet and social media use and quality of life,
      depression, cognitive function and sleep problems in HD patients. METHODS: The
      study is cross-sectional in design. All patients underwent history taking;
      physical examination; laboratory analysis and quality of life (by a short form of
      the Medical Outcomes Study), depression (by the Beck Depression Inventory),
      cognitive function (by the Standardized Mini Mental State Examination) and sleep
      problems (by the Pittsburgh Sleep Quality Index) evaluation. RESULTS: In total,
      134 HD patients (male/female: 73/61, age: 53.0 +/- 13.4 years) were included.
      Patients with mail, Facebook and Twitter accounts were younger, were less
      depressive, had better quality of life, had higher cognitive function and were
      more educated compared to patients who did not have these accounts. Patients with
      Internet-based research about their disease were less depressive, had better
      quality of life and sleep quality, had higher cognitive function and were more
      educated compared to patients who did not have Internet-based research.
      CONCLUSION: Internet and social media use was closely related with quality of
      life, depression, cognitive function and education in HD patients. Studies are
      needed on whether Internet use under the supervision of health care professionals
      will improve clinical outcomes, adherence, quality of life, depression and
      decision making in HD patients.

PMID- 23948576
TI  - Antitumor properties of five-coordinate gold(III) complexes bearing substituted
      polypyridyl ligands.
AB  - In an on-going effort to discover metallotherapeutic alternatives to the
      chemotherapy drug cisplatin, neutral distorted square pyramidal gold(III)
      coordination complexes possessing 2,9-disubstituted-1,10-phenanthroline ligands
      {[((R)phen)AuCl3]; R = n-butyl, sec-butyl} have been previously synthesized and
      characterized. A structurally analogous gold(III) complex bearing a 6,6'-di
      methylbipyridine ligand ([((methyl)bipy)AuCl3]) has been synthesized and fully
      characterized to probe the effect of differing aromatic character of the ligand
      on solution stability and tumor cell cytotoxicity. The two compounds [((sec
      butyl)phen)AuCl3] and [((methyl)bipy)AuCl3]) were subsequently assessed for their
      stability against the biological reductant glutathione, and it was found that the
      [((sec-butyl)phen)AuCl3] complex exhibits slightly enhanced stability compared to
      the [((methyl)bipy)AuCl3] complex and significantly higher stability than
      previously reported square planar gold(III) complex ions. Furthermore, these
      complexes were tested for cytotoxic effects against existing lung and head and
      neck cancer cell lines in vitro. The [((sec-butyl)phen)AuCl3] complex was found
      to be more cytotoxic than cisplatin against five different tumor cell lines,
      whereas [((methyl)bipy)AuCl3] had more limited in vitro antitumor activity. Given
      that [((sec-butyl)phen)AuCl3] had significantly higher antitumor activity, it was
      tested against an in vivo tumor model. It was found that this complex did not
      significantly reduce the growth of xenograft tumors in mice and initial model
      binding studies with bovine serum albumin indicate that interactions with serum
      albumin proteins may be the cause for the limited in vivo activity of this
      potential metallotherapeutic.

PMID- 23948577
TI  - Antioxidant capacity and DNA-interaction studies of zinc complexes with a non
      steroidal anti-inflammatory drug, mefenamic acid.
AB  - Zinc(II) complexes of a non-steroidal anti-inflammatory drug, mefenamic
      acid(=Hmef) in the absence or presence of the nitrogen donor heterocyclic ligands
      2,2'-bipyridine(=bipy), 2,2'-bipyridylamine(=bipyam), 2,2'-dipyridylketone
      oxime(=Hpko) or 1,10-phenanthroline(=phen) have been synthesized and
      characterized. The crystal structures of [Zn(mef-O,O')2(bipy)], 2, [Zn(mef
      O)2(Hpko-N,N')2].EtOH, 4 and [Zn(mef-O)(mef-O,O')(phen)(H2O)], 5, have been
      determined by X-ray crystallography showing distinct binding modes of mefenamato
      carboxylato group, bidentate in 2, monodentate in 4 or both in 5. Interaction
      studies of the complexes with calf-thymus DNA (CT DNA) have shown that complexes
      can bind to CT DNA with [Zn(mef-O)2(Hpko)2] exhibiting the highest binding
      constant to CT DNA (Kb = 1.93(+/-0.04) * 10(7) M(-1)). The complexes can bind to
      CT DNA via intercalation as concluded by DNA solution viscosity measurements.
      Competitive studies with ethidium bromide (EB) have shown that the complexes can
      displace the DNA-bound EB. The complexes exhibit good binding affinity to serum
      albumin proteins with [Zn(mef-O)2(H2O)4], 1 exhibiting the highest quenching
      ability (kq = 1.46 * 10(15) M(-1) s(-1) for human and 5.55 * 10(15) M(-1) s(-1)
      for bovine serum albumin). All compounds have been tested for their antioxidant
      and free radical scavenging activity as well as for their in vitro inhibitory
      activity against soybean lipoxygenase. The scavenging activity is low to moderate
      against 1,1-diphenyl-picrylhydrazyl (DPPH) radicals and high against hydroxyl and
      2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(+.)) radicals, with
      [Zn(mef-O)2(H2O)4], 1 (ABTS%, 0.1 mM: 94.75(+/-1.06)%; (.)OH%, 0.1mM: 96.69(+/
      0.27)%; LOX: IC50 = 27.34(+/-0.90) MUM) exhibiting the highest scavenging
      activity of the ABTS radical cation among the complexes. Additionally, the
      complexes exhibit higher scavenging and LOX inhibitory activity than free
      mefenamic acid (ABTS%, 0.1 mM: 66.32(+/-0.38)%; (.)OH%, 0.1 mM: 92.51(+/-0.44)%;
      LOX: IC50 = 48.52(+/-0.88) MUM).

PMID- 23948578
TI  - Syntheses and crystal structures of tetracopper(II) complexes bridged by
      asymmetric N,N'-bis(substituted)oxamides: Molecular docking, DNA-binding and in
      vitro anticancer activity.
AB  - Two new tetranuclear copper(II) complexes of the formulae
      [Cu4(oxbm)2(phen)2](NO3)2?6H2O (1) and [Cu4(oxbpa)2(phen)2](ClO4)2.4H2O (2),
      where H3oxbm and H3oxbpa stand for N-(2-aminopropyl)-N'- (2
      carboxylatophenyl)oxamide and N-hydroxypropyl-N'-(2-carboxylatophenyl)oxamide,
      respectively, and phen is 1,10-phenanthroline, have been synthesized and
      characterized by elemental analyses, molar conductivity measurements, IR and
      electronic spectrum studies, and X-ray single crystal diffraction. In the two
      tetracopper(II) complexes, the presence of the circular tetracopper(II) cations
      is assembled by a pair of cis-oxamido-bridged dicopper(II) units through carboxyl
      bridges, in which Cu1 is located in a distorted square-planar environment, while
      Cu2 is in a distorted square-pyramidal geometry. Numerous hydrogen bonds link
      complex 1 or 2 into a 2-D infinite network. The interactions of the two
      tetracopper(II) complexes with DNA are investigated both theoretically and
      experimentally, revealing that these tetracopper(II) complexes can interact with
      HS-DNA in the mode of intercalation, and complex 1 possesses stronger
      intercalating ability. The molecular docking of the two tetranuclear copper(II)
      complexes with the self-complementary DNA duplex of sequence d(ACCGACGTCGGT)2
      facilitates the binding events. Cytotoxicity experiments indicate that the two
      tetracopper(II) complexes exhibit cytotoxic effects against human hepatocellular
      carcinoma cell SMMC-7721 and human lung adenocarcinoma cell A549. Interestingly,
      the cytotoxic activities of the two tetracopper(II) complexes are consistent with
      their DNA-binding abilities, following the order of 1>2. The main results suggest
      that different bridging ligands in tetracopper(II) complexes may play an
      important role in the DNA-binding properties and cytotoxic activities.

PMID- 23948579
TI  - Cortical bone-derived stem cells: a novel class of cells for myocardial
      protection.

PMID- 23948580
TI  - Inhibitor kappaB kinase: another node in the cell signaling network regulating
      smooth muscle contraction.

PMID- 23948582
TI  - Is tumor necrosis factor-alpha friend or foe for chronic heart failure?
AB  - Although detrimental effects of tumor necrosis factor-alpha (TNF-alpha) have been
      reported in failing myocardium, clinical trials using TNF-alpha antagonists did
      not show the benefit of TNF-alpha inhibition in patients with chronic heart
      failure (CHF). The double-edged effects of TNF-alpha/Toll-like receptors (TLRs)
      related proinflammatory cytokines and downstream signal transduction, nuclear
      factor (NF)-kappaB activation on failing myocardium are discussed.

PMID- 23948581
TI  - Through thick and thin: a circulating growth factor inhibits age-related cardiac
      hypertrophy.
AB  - In an intriguing new study, Loffredo et al report that joining the circulation of
      old mice with that of young mice reduces age-related cardiac hypertrophy. They
      also found that the growth factor growth/differentiation factor 11 is a
      circulating negative regulator of cardiac hypertrophy which suggests that raising
      growth/differentiation factor 11 levels may be useful to treat cardiac
      hypertrophy associated with aging.

PMID- 23948584
TI  - Cardiovascular RNA interference therapy: the broadening tool and target spectrum.
AB  - Understanding of the roles of noncoding RNAs (ncRNAs) within complex organisms
      has fundamentally changed. It is increasingly possible to use ncRNAs as
      diagnostic and therapeutic tools in medicine. Regarding disease pathogenesis, it
      has become evident that confinement to the analysis of protein-coding regions of
      the human genome is insufficient because ncRNA variants have been associated with
      important human diseases. Thus, inclusion of noncoding genomic elements in
      pathogenetic studies and their consideration as therapeutic targets is warranted.
      We consider aspects of the evolutionary and discovery history of ncRNAs, as far
      as they are relevant for the identification and selection of ncRNAs with likely
      therapeutic potential. Novel therapeutic strategies are based on ncRNAs, and we
      discuss here RNA interference as a highly versatile tool for gene silencing. RNA
      interference-mediating RNAs are small, but only parts of a far larger spectrum
      encompassing ncRNAs up to many kilobasepairs in size. We discuss therapeutic
      options in cardiovascular medicine offered by ncRNAs and key issues to be solved
      before clinical translation. Convergence of multiple technical advances is
      highlighted as a prerequisite for the translational progress achieved in recent
      years. Regarding safety, we review properties of RNA therapeutics, which may
      immunologically distinguish them from their endogenous counterparts, all of which
      underwent sophisticated evolutionary adaptation to specific biological contexts.
      Although our understanding of the noncoding human genome is only fragmentary to
      date, it is already feasible to develop RNA interference against a rapidly
      broadening spectrum of therapeutic targets and to translate this to the clinical
      setting under certain restrictions. 

PMID- 23948583
TI  - New and TALENted genome engineering toolbox.
AB  - Recent advances in the burgeoning field of genome engineering are accelerating
      the realization of personalized therapeutics for cardiovascular disease. In the
      postgenomic era, sequence-specific gene-editing tools enable the functional
      analysis of genetic alterations implicated in disease. In partnership with high
      throughput model systems, efficient gene manipulation provides an increasingly
      powerful toolkit to study phenotypes associated with patient-specific genetic
      defects. Herein, this review emphasizes the latest developments in genome
      engineering and how applications within the field are transforming our
      understanding of personalized medicine with an emphasis on cardiovascular
      diseases. 

PMID- 23948586
TI  - Regulation of cardiac L-type Ca2+ channel CaV1.2 via the beta-adrenergic-cAMP
      protein kinase A pathway: old dogmas, advances, and new uncertainties.
AB  - In the heart, adrenergic stimulation activates the beta-adrenergic receptors
      coupled to the heterotrimeric stimulatory Gs protein, followed by subsequent
      activation of adenylyl cyclase, elevation of cyclic AMP levels, and protein
      kinase A (PKA) activation. One of the main targets for PKA modulation is the
      cardiac L-type Ca2+ channel (CaV1.2) located in the plasma membrane and along the
      T-tubules, which mediates Ca2+ entry into cardiomyocytes. beta-Adrenergic
      receptor activation increases the Ca2+ current via CaV1.2 channels and is
      responsible for the positive ionotropic effect of adrenergic stimulation. Despite
      decades of research, the molecular mechanism underlying this modulation has not
      been fully resolved. On the contrary, initial reports of identification of key
      components in this modulation were later refuted using advanced model systems,
      especially transgenic animals. Some of the cardinal debated issues include
      details of specific subunits and residues in CaV1.2 phosphorylated by PKA, the
      nature, extent, and role of post-translational processing of CaV1.2, and the role
      of auxiliary proteins (such as A kinase anchoring proteins) involved in PKA
      regulation. In addition, the previously proposed crucial role of PKA in
      modulation of unstimulated Ca2+ current in the absence of beta-adrenergic
      receptor stimulation and in voltage-dependent facilitation of CaV1.2 remains
      uncertain. Full reconstitution of the beta-adrenergic receptor signaling pathway
      in heterologous expression systems remains an unmet challenge. This review
      summarizes the past and new findings, the mechanisms proposed and later proven,
      rejected or disputed, and emphasizes the essential issues that remain unresolved.

PMID- 23948587
TI  - Prognostic microRNAs after AMI.

PMID- 23948588
TI  - Response to the letter by Devaux et al.

PMID- 23948589
TI  - Structural elucidation of full-length nidogen and the laminin-nidogen complex in
      solution.
AB  - Nidogen-1 is a key basement membrane protein that is required for many biological
      activities. It is one of the central elements in organizing basal laminae
      including those in the skin, muscle, and the nervous system. The self-assembling
      extracellular matrix that also incorporates fibulins, fibronectin and integrins
      is clamped together by networks formed between nidogen, perlecan, laminin and
      collagen IV. To date, the full-length version of nidogen-1 has not been studied
      in detail in terms of its solution conformation and shape because of its
      susceptibility to proteolysis. In the current study, we have expressed and
      purified full-length nidogen-1 and have investigated its solution behavior using
      size-exclusion chromatography (SEC), dynamic light scattering (DLS) and small
      angle X-ray scattering (SAXS). The ab initio shape reconstruction of the complex
      between nidogen-1 and the laminin gamma-1 short arm confirms that the interaction
      is mediated solely by the C-terminal domains: the rest of the domains of both
      proteins do not participate in complex formation. 

PMID- 23948585
TI  - Cardiac metabolism and its interactions with contraction, growth, and survival of
      cardiomyocytes.
AB  - The network for cardiac fuel metabolism contains intricate sets of interacting
      pathways that result in both ATP-producing and non-ATP-producing end points for
      each class of energy substrates. The most salient feature of the network is the
      metabolic flexibility demonstrated in response to various stimuli, including
      developmental changes and nutritional status. The heart is also capable of
      remodeling the metabolic pathways in chronic pathophysiological conditions, which
      results in modulations of myocardial energetics and contractile function. In a
      quest to understand the complexity of the cardiac metabolic network,
      pharmacological and genetic tools have been engaged to manipulate cardiac
      metabolism in a variety of research models. In concert, a host of therapeutic
      interventions have been tested clinically to target substrate preference, insulin
      sensitivity, and mitochondrial function. In addition, the contribution of
      cellular metabolism to growth, survival, and other signaling pathways through the
      production of metabolic intermediates has been increasingly noted. In this
      review, we provide an overview of the cardiac metabolic network and highlight
      alterations observed in cardiac pathologies as well as strategies used as
      metabolic therapies in heart failure. Lastly, the ability of metabolic
      derivatives to intersect growth and survival are also discussed. 

PMID- 23948591
TI  - On the TRAIL of obesity and diabetes.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been
      extensively studied for its preferential ability to induce apoptosis of cancer
      cells. Beyond the cytotoxic capacity of TRAIL, new physiological and pathological
      roles for TRAIL have been identified, and there is now growing evidence
      supporting its involvement in the development of obesity and diabetes. This
      review summarizes the most recent findings associating TRAIL with obesity and
      diabetes in both humans and experimental settings. We also present and discuss
      some of the reported controversies behind TRAIL signaling and function.
      Understanding TRAIL mechanism(s) in vivo and its involvement in disease may lead
      to novel strategies to combat the growing pandemic of obesity and diabetes
      worldwide. 

PMID- 23948590
TI  - When less is more: novel mechanisms of iron conservation.
AB  - Disorders of iron homeostasis are very common, yet the molecular mechanisms of
      iron regulation remain understudied. Over 20 years have passed since the first
      characterization of iron-regulatory proteins (IRP) as mediators of cellular iron
      deficiency response in mammals through iron acquisition. However, little is known
      about other mechanisms necessary for adaptation to low-iron states. In this
      review, we present recent evidence that establishes the existence of a new iron
      regulatory pathway aimed at iron conservation and optimization of iron use
      through suppression of nonessential iron-consuming processes. Moreover, we
      discuss the possible links between iron homeostasis and energy metabolism
      uncovered by studies of iron-deficiency response. 

PMID- 23948592
TI  - Comparison between the effects of diallyl tetrasulfide on human retina pigment
      epithelial cells (ARPE-19) and HCT116 cells.
AB  - BACKGROUND: Diallyl mono- and polysulfanes from garlic are known to induce an
      adaptive cell response and the formation of antioxidants in cancer cells. In the
      case of a severe ER stress and a failure in the response, cancer cells eventually
      go into apoptosis. Only little is known about the response of normal cells upon
      treatment. METHODS: Normal ARPE-19 cells were treated with diallyl tetrasulfide
      to study their cellular response and the results were compared with those of
      HCT116 cancer cells. Cell viability was checked by an MTT assay and
      cytofluorimetry. The formation of superoxide radicals, H2O2 and thiols were
      determined and proteins involved in the ER stress response were also detected by
      Western blot analysis. RESULTS: We found that diallyl tetrasulfide induced
      reactive oxygen species (ROS) in normal cells similar to cancer cells in a time
      (0 to 60min) and dose dependent manner (0 to 50MUM). The level of heme oxigenase
      1 (HO-1) was up-regulated in both cell types. Initially, we found a decrease in
      the total thiol level in both cell types but in contrast to cancer cells, normal
      cells recovered from the decrease in the total thiol concentration within 60min
      of treatment. CONCLUSIONS: The recovery of the thiol concentration in normal
      cells treated with diallyl tetrasulfide seems to be responsible for the failure
      to induce the ER stress signalling pathway and finally apoptosis in normal cells.
      GENERAL SIGNIFICANCE: The difference in the recovery of the thiol status might be
      an explanation for the anti-carcinogenic effects of garlic compounds.

PMID- 23948593
TI  - Glutathione controls the redox state of the mitochondrial carnitine/acylcarnitine
      carrier Cys residues by glutathionylation.
AB  - BACKGROUND: The mitochondrial carnitine/acylcarnitine carrier (CAC) is essential
      for cell metabolism since it catalyzes the transport of acylcarnitines into
      mitochondria allowing the beta-oxidation of fatty acids. CAC functional and
      structural properties have been characterized. Cys residues which could form
      disulfides suggest the involvement of CAC in redox switches. METHODS: The effect
      of GSH and GSSG on the [(3)H]-carnitine/carnitine antiport catalyzed by the CAC
      in proteoliposomes has been studied. The Cys residues involved in the redox
      switch have been identified by site-directed mutagenesis. Glutathionylated CAC
      has been assessed by glutathionyl-protein specific antibody. RESULTS: GSH led to
      increase of transport activity of the CAC extracted from liver mitochondria. A
      similar effect was observed on the recombinant CAC. The presence of glutaredoxin
      1 (Grx1) accelerated the GSH activation of the recombinant CAC. The effect was
      more evident at 37 degrees C. GSSG led to transport inhibition which was reversed
      by dithioerythritol (DTE). The effects of GSH and GSSG were studied on CAC Cys
      mutants. CAC lacking C136 and C155 was insensitive to both reagents. Mutants
      containing these two Cys responded as the wild-type. Anti-glutathionyl antibody
      revealed the formation of glutathionylated CAC. CONCLUSIONS: CAC is redox
      sensitive and it is regulated by the GSH/GSSG couple. C136 and C155 are
      responsible for the regulation which occurs through glutathionylation. GENERAL
      SIGNIFICANCE: CAC is sensitive to the redox state of the cell switching between
      oxidized and reduced forms in response to variation of GSSG and GSH
      concentrations.

PMID- 23948594
TI  - Arteriolar diameter and spontaneous vasomotion: importance of potassium channels
      and nitric oxide.
AB  - Arterioles display cyclic variations in diameter, termed vasomotion initiated by
      smooth muscle cells (SMCs), but the endothelium should also be evaluated due to
      its modulatory role on vessel tone. Since nitric oxide (NO) and prostacyclin
      (PGI2) regulate SMC tone and activate K(+) currents, we have investigated their
      role on vasomotion, by observing effects of topical application of N(omega)-nitro
      l-arginine (L-NA, NO synthesis inhibitor), glibenclamide (KATP channel
      inhibitor), sodium nitroprusside (SNP, NO donor), iloprost (PGI2 analogue) and
      methylene blue (MB, cGMP production inhibitor) on the cheek pouch preparation of
      anesthetized male hamsters. L-NA (10(-10)-10(-6)M) induced vasoconstriction,
      reduction and abolition of vasomotion. MB (10(-7) to 10(-5)M) reduced mean
      arteriolar diameter with no changes on vasomotion. In the presence of 10(-6)M of
      MB, addition of 10(-6)L-NA totally abolished vasomotion without further
      constriction. Glibenclamide (10(-6)M) in the presence of L-NA at equimolar
      concentration restored both vasomotion frequency and amplitude. This effect was
      not observed in the presence of TEA 5mM. SNP (10(-10)-10(-6)M) induced a dose
      dependent increase of arteriolar diameter and decreased vasomotion. Iloprost (10(
      12)-10(-6)M) induced a concentration dependent increase of arteriolar diameter,
      reduced vasomotion frequency, but in lower concentrations (10(-12)-10(-10)M)
      increased its amplitude and in higher concentrations (10(-9)-10(-6)M) decreased
      it. SNP and iloprost inhibited vasomotion at 10(-7)M; however, at this
      concentration SNP and iloprost induced an increment of 35% and 50% of the initial
      arteriolar diameter, respectively. In the presence of L-NA (10(-6)M), vasomotion
      was restored by SNP at 10(-10)M and iloprost 10(-12)M, which corresponded to 80%
      of the initial diameter value. Around the initial (control) arteriolar diameter
      value, vasomotion presented its highest frequencies and amplitudes. Cessation of
      vasomotion occurred with L-NA (10(-6)M) in the presence of SNP (10(-6)M) and
      iloprost (10(-7)M) when arteriolar diameter reached 150% and 120% of its initial
      value, respectively. In conclusion, the present study strongly suggests that
      vasomotion (1) is not solely related to vascular tone, (2) needs an interplay
      between vascular tone and membrane currents and (3) could be modulated by NO (but
      not cGMP) and KATP channels. In addition, our results point to the existence of
      dissociation between vasomotion frequency and amplitude. 

PMID- 23948595
TI  - Suppression of cyclin D1 by plasmid-based short hairpin RNA ameliorated
      experimental pulmonary vascular remodeling.
AB  - Our previous study has demonstrated that a plasmid-based short hairpin RNA
      (shRNA) against cyclin D1 could attenuate the pulmonary artery smooth muscle cell
      (PASMC) proliferation and pulmonary vascular remodeling in smoking rats. In this
      report, we examined the efficiency of this shRNA plasmid in monocrotaline-induced
      pulmonary vascular remodeling. A single injection of monocrotaline induced
      pulmonary vascular remodeling and cyclin D1 over-expression in pulmonary vascular
      smooth muscle. The shRNA successfully suppressed the up-regulation of cyclin D1
      in pulmonary vessels of monocrotaline-treated rats. Moreover, this shRNA
      decreased the percentage of muscularized vessels and the wall thickness of
      pulmonary vessels. So, we concluded that plasmid-based shRNA against cyclin D1
      ameliorated pulmonary vascular remodeling in monocrotaline-treated rats. Cyclin
      D1 might be a potential target for the therapy of pulmonary vascular remodeling
      and pulmonary hypertension. 

PMID- 23948596
TI  - HMGB1: a potential target for treatment of benign prostatic hyperplasia.
AB  - Previous studies have demonstrated an increased incidence of benign prostatic
      hyperplasia (BPH) in men with prostatitis. In addition to androgens and age,
      recent studies also pointed to an important role for inflammation in causing and
      promoting the progression of BPH. Inflammatory infiltrates are frequently
      observed in prostate tissue specimens, and the degree of inflammation has been
      correlated with prostate volume and weight. Furthermore, a pro-inflammatory
      microenvironment is closely related to BPH stromal hyperproliferation and tissue
      remodeling, although its role in BPH remains unclear. Accumulating evidence
      indicates that HMGB1 acts as a potent proinflammatory cytokine that contributes
      to the pathogenesis of many inflammatory and infectious disorders. Experimental
      studies also reported that HMGB1 promotes cell chemotaxis and proliferation.
      These observations led us to propose that HMGB1 contributes to the progress of
      BPH, and that targeting the HMGB1 signaling pathway might be a new strategy to
      treat prostatic enlargement. 

PMID- 23948597
TI  - Hypothesis: smoking decreases breast feeding duration by suppressing prolactin
      secretion.
AB  - A number of studies, including new data summarized here, conclude that breast
      feeding duration is lower in smoking mothers. Although some have suggested that
      this merely reflects poor health motivation in those prone to smoke, several
      lines of evidence support the view that chronic smoking does indeed compromise
      breast feeding by suppressing prolactin secretion and thereby lowering breast
      milk volume. Moreover, a recent clinical trial shows that an effective smoking
      cessation program can boost breast feeding duration in smokers. An analysis of
      pertinent rodents studies suggests that chronic nicotine administration boosts
      dopaminergic activity in the tuberoinfundibular tract which functions to inhibit
      prolactin release; this increase in dopaminergic activity, in turn, may reflect a
      nicotine-mediated suppression of hypothalamic opioid activity. 

PMID- 23948598
TI  - Spinal cord injury models in non human primates: are lesions created by sharp
      instruments relevant to human injuries?
AB  - The worldwide incidence of traumatic spinal cord injury (SCI) is approximated at
      180,000 new cases per year. Experiments using nonhuman primates (NHP) are often
      used to replicate the human condition in order to advance the understanding of
      SCI and to assist in the development of new treatments. Experimental spinal cord
      lesions in NHP have been created by a number of methods including blunt trauma,
      epidural balloons, circumferential cuffs, and dropping a precision weight over
      the spinal cord. As well, experimental lesions have been created with sharp
      instruments after opening the dura mater. However, spinal cord lesions that are
      created with a sharp instrument in NHP experiments may not replicate the clinical
      and pathological features of human spinal cord injury. Researchers should
      recognize the challenges associated with making clinical inferences in human SCIs
      based on NHP experiments that created experimental lesions with a sharp surgical
      instrument. 

PMID- 23948599
TI  - Rationale for an experimental treatment of retinitis pigmentosa: 140-month test
      of hypothesis with one patient.
AB  - BACKGROUND: Numerous mutations in over 100 rod genes are the well-established
      cause of apoptotic death of these cells and development of night blindness in
      retinitis pigmentosa (RP). Cone death is either concomitant or follows rod death
      with resultant loss of critical peripheral and central day vision. As cones are
      generally not encumbered by genetic mutations, the causes of their death and its
      prevention are the central problems of RP research. Currently no FDA-approved
      medications are available for retarding RP progression. HYPOTHESIS: It is
      proposed that cones, which are outnumbered 20:1 by rods, undergo apoptosis as a
      consequence of neurotrophic factor deficiencies and oxidative stresses
      accompanying massive rod death: increased retinal oxygen tension; leakage of
      lipid-peroxidation catalysts from disrupted membranes; reactive oxygen species
      from active/hyperactive microglia ingesting rod-apoptotic bodies. Accordingly we
      developed and tested a treatment regimen with a range of antioxidants in
      combination with the off-label use of deprenyl (1 mg/day), a safe antiapoptotic
      agent, which also upregulates eight neurotrophic factors. Since deprenyl inhibits
      only one of four mitochondrial apoptotic pathways, we added the antibiotic
      minocycline (100 mg/day) to our protocol at month 76. Minocycline complements
      deprenyl's therapeutic properties: it inhibits all four apoptotic pathways;
      inhibits apoptosis-initiating proteins; as phenol exerts powerful antioxidant
      properties; upregulates three antioxidant enzymes; downregulates
      oxidative/inflammatory microglia activities. Its safe long-term use for acne and
      rheumatoid arthritis received FDA approval; it passes the blood/brain and
      blood/retinal barriers readily; and because of its rapid and complete absorption
      causes no intestinal disturbances. The National Eye Institute has initiated in
      2010 and 2011 clinical trials with minocycline (200 mg/day) for diabetic macular
      edema and retinal branch vein occlusion. TESTING OF HYPOTHESIS: The hypothesis
      was tested for 140 months with one RP patient monitored by Humphrey Perimetry,
      which was quantitated by two parameters: (a) sum of decibel units, (b) number of
      detected light sources (visual field). Although no decline was observed in these
      parameters during the first 50 months of treatment, they declined by 10-28%
      during months 50-65. These declines reversed upon introduction of minocycline:
      over the total 140-month treatment, the right eye visual field showed 0% decline
      and left eye 13.3% decline. Rate constants for logarithmic decline of visual
      field measured prior to treatment indicate that visual fields would have
      decreased by 64% and 70%, respectively by month 140 in the absence of treatment.

PMID- 23948600
TI  - A new therapy for refractory partial epilepsy: current shunt.
AB  - A large number of epileptic patients suffer from refractory epilepsy, despite
      optimal treatment; thus these patients require new therapeutic approaches. Focal
      seizure activity is typically initiated in a fixed and localized region, which
      subsequently spreads to neighboring regions or more distant areas. At the initial
      onset of a seizure, the epileptic discharge will generate a relatively high
      voltage in seizure focus, and the discharge subsequently spreads to other
      relatively low-voltage regions. However, it is unknown whether seizure can be
      controlled through current shunt using a conduction microelectrode to conduct the
      epileptic discharge with a relatively high voltage in the seizure focus outside
      the brain. The current therapies for epilepsy, including drugs, resective surgery
      and neuromodulation, focus on inhibiting abnormal excessive or synchronous
      neuronal activity to control seizures; thus, the basic mechanism underlying these
      therapies is "inhibition". In contrast, we proposed a "conduction" mechanism,
      whereby a current shunt with conduction electrode is used to control seizures. To
      our knowledge, this therapeutic strategy has not been previously reported, and we
      propose that this approach might be an alternative choice for the treatment of
      refractory partial epilepsy in the future. 

PMID- 23948601
TI  - Synthetic oxytocin and breastfeeding: reasons for testing an hypothesis.
AB  - Synthetic oxytocin is widely used in developed countries and in emerging
      countries as well. It is the most common medical intervention in childbirth. A
      great variety of side effects are plausible. There are in particular theoretical
      reasons to test the hypothesis that the increasing incidence of breastfeeding
      difficulties and the frequent earlier than desired cessation of breastfeeding are
      related to the use of synthetic oxytocin during labour. There have already been
      some studies that tend to support this hypothesis. Four hundred of the 7465
      children born in 2006 at the Carlos Haya University Hospital (Malaga, Spain) were
      randomly selected. By interviewing the mothers, information about feeding type
      and duration was obtained in 2011 for 316 children. Among the 189 children who
      were born after labours induced or augmented with synthetic oxytocin, the odds
      ratio for bottle-feeding was 1.451 and the odds ratio for withdrawal at 3 months
      was 2.294. In addition, the Battelle Developmental Inventory was used to assess
      at age five 148 children (84 born with synthetic oxytocin): the odds ratio for
      neuropsychological development disorders after use of oxytocin was 1.46. The main
      limitation of such a preliminary study is that in the context of a tertiary
      Spanish hospital the possible effects of synthetic oxytocin on the quality and
      duration of breastfeeding cannot be easily dissociated from the effects of other
      components of pharmacological assistance during labour, particularly epidural
      fentanyl (a synthetic opioid analgesic). This comment is valid for all studies
      exploring the side effects of synthetic oxytocin in obstetric units of developed
      countries, including explorations through videotapes of the effects of synthetic
      oxytocin on primitive neonatal reflexes. It is also valid for studies exploring
      the side effects of obstetric analgesia without taking into account the use of
      synthetic oxytocin. This is why we underline the importance of conducting such
      studies in emerging countries (e.g. China and Brazil) where synthetic oxytocin is
      widely used while there are no epidural services. Studies of oxytocin given
      electively at the onset of third stage of labour (after the birth of the neonate)
      should help to interpret possible effects on the quality and duration of
      breastfeeding.

PMID- 23948602
TI  - Evolutionary hypothesis for Chiari type I malformation.
AB  - Chiari I malformation (CM-I) is classically defined as a cerebellar tonsillar
      herniation (>=5 mm) through the foramen magnum. A decreased posterior fossa
      volume, mainly due to basioccipital hypoplasia and sometimes platybasia, leads to
      posterior fossa overcrowding and consequently cerebellar herniation. Regardless
      of radiological findings, embryological genetic hypothesis or any other
      postulations, the real cause behind this malformation is yet not well-elucidated
      and remains largely unknown. The aim of this paper is to approach CM-I under a
      broader and new perspective, conjoining anthropology, genetics and neurosurgery,
      with special focus on the substantial changes that have occurred in the posterior
      cranial base through human evolution. Important evolutionary allometric changes
      occurred during brain expansion and genetics studies of human evolution
      demonstrated an unexpected high rate of gene flow interchange and possibly
      interbreeding during this process. Based upon this review we hypothesize that CM
      I may be the result of an evolutionary anthropological imprint, caused by
      evolving species populations that eventually met each other and mingled in the
      last 1.7 million years.

PMID- 23948604
TI  - Creation and implementation of a national emergency medicine fourth-year student
      examination.
AB  - BACKGROUND: A National Board of Medical Examiners examination does not exist for
      Emergency Medicine (EM) students. To fill this void, the Clerkship Directors in
      Emergency Medicine tasked a committee with development of an examination for 4th
      year (M4) EM students, based on a published syllabus, and consisting of questions
      written according to published question-writing guidelines. STUDY OBJECTIVES:
      Describe examination development and statistics at 9 months. METHODS: The
      committee reviewed an existing EM student question database at www.saemtests.org
      for statistical performance, compliance with item-writing guidelines, and topic
      inclusion within the published EM M4 syllabus. For syllabus topics without
      existing questions, committee members wrote new items. LXR 6.0 software (Applied
      Measurement Professionals, Inc., Georgetown, SC) was used for examination
      administration. Data gathered included numbers of examinations completed, mean
      scores with SD, and point biserial correlation (rpb). RESULTS: Of the 553
      questions assessed, 157 questions met the stated criteria, and 37 were included
      in the examination. Thirteen new questions were written by committee members to
      cover all curriculum topics. The National EM M4 Examination was released online
      August 1, 2011. Nine months later, the examination had been completed 1642 times
      by students from 27 clerkships. Mean score was 79.69% (SD 3.89). Individual
      question difficulties ranged from 26% to 99%. Question rpbs ranged from 0.067 to
      0.353, mean 0.213 (SD 0.066). CONCLUSIONS: A national group of EM educators
      developed an examination to assess a published clerkship syllabus. The
      examination contains questions written according to published item-writing
      guidelines, and exhibits content validity, appropriate difficulty levels, and
      adequate question discriminatory ability.

PMID- 23948605
TI  - New insights for the risk of bisphenol A: inhibition of UDP
      glucuronosyltransferases (UGTs).
AB  - Bisphenol A (BPA), the important endocrine-disrupting chemical (EDC), has been
      reported to be able to induce various toxicity. The present study aims to
      understand the toxicity behavior of bisphenol A through evaluating the inhibition
      profile of bisphenol A towards UDP-glucuronosyltransferase (UGT) isoforms. In
      vitro recombinant UGTs-catalyzed 4-methylumbelliferone (4-MU) glucuronidation
      reaction was employed as probe reaction for all the tested UGT isoforms. The
      results showed that bisphenol A exerted stronger inhibition towards UGT2B
      isoforms than UGT1A isoforms. Furthermore, the inhibition kinetic type and
      parameters (K(i)) were determined for the inhibition of bisphenol A towards
      UGT2B4, 2B7, 2B15, and 2B17. Bisphenol A exhibited the competitive inhibition
      towards UGT2B4, and noncompetitive inhibition towards UGT2B7, 2B15 and 2B17. The
      inhibition kinetic parameters (K(i)) were calculated to be 1.1, 32.6, 5.6, and
      19.9 MUM for UGT2B4, 2B7, 2B15 and 2B17, respectively. In combination with the in
      vivo concentration of bisphenol A, the elevation of exposure dose was predicted
      to increase by 29.1%, 1%, 5.7%, and 1.6% for UGT2B4, 2B7, 2B15, and 2B17,
      indicating the high influence of bisphenol A towards the in vivo UGT2B isofroms
      mediated metabolism of xenobiotics and endogenous substances. All these data
      provide the supporting information for deeper understanding of toxicology of
      bisphenol A.

PMID- 23948603
TI  - Serum regulation of Id1 expression by a BMP pathway and BMP responsive element.
AB  - Immediate early genes (IEGs) are expressed upon re-entry of quiescent cells into
      the cell cycle following serum stimulation. These genes are involved in growth
      control and differentiation and hence their expression is tightly controlled.
      Many IEGs are regulated through Serum Response Elements (SREs) in their
      promoters, which bind Serum Response Factor (SRF). However, many other IEGs do
      not have SREs in their promoters and their serum regulation is poorly understood.
      We have identified SRF-independent IEGs in SRF-depleted fibroblasts. One of
      these, Id1, was examined more closely. We mapped a serum responsive element in
      the Id1 promoter and find that it is identical to a BMP responsive element (BRE).
      The Id1 BRE is necessary and sufficient for the serum regulation of Id1.
      Inhibition of the BMP pathway by siRNA depletion of Smad 4, treatment with the
      BMP antagonist noggin, or the BMP receptor inhibitor dorsomorphin blocked serum
      induction of Id1. Further, BMP2 is sufficient to induce Id1 expression. Given
      reports that SRC inhibitors can block Id1 expression, we tested the SRC
      inhibitor, AZD0530, and found that it inhibits the serum activation of Id1.
      Surprisingly, this inhibition is independent of SRC or its family members.
      Rather, we show that AZD0530 directly inhibits the BMP type I receptors. Serum
      induction of the Id1 related gene Id3 also required the BMP pathway. Given these
      and other findings we conclude that the Id family of IEGs is regulated by BMPs in
      serum through similar BREs. This represents a second pathway for serum regulation
      of IEGs. 

PMID- 23948606
TI  - Variations in dissipation rate, microbial function and antibiotic resistance due
      to repeated introductions of manure containing sulfadiazine and chlortetracycline
      to soil.
AB  - Antibiotic persistence following five successive treatments of sulfadiazine (SDZ)
      and chlortetracycline (CTC), alone and in combination, in manure-amended soil was
      studied under laboratory conditions. The resulting effects on soil respiration
      and enzyme activities as well as pollution-induced community tolerance, were also
      examined. A trend of initial suppression followed by recovery was observed in the
      dissipation rates of SDZ or CTC during the antibiotic treatments, and combined
      treatment with both antibiotics did not alter the respective dissipation rates
      significantly. Soil respiration activity with SDZ and/or CTC treatments was
      inhibited during the initial two treatments; however, the activity thereafter
      recovered to or exceeded the level of the individual manure treatment. Initially,
      soil urease and dehydrogenase activities were not affected; however, after the
      fifth treatment, these activities were significantly stimulated in the CTC
      individual and combined treatments compared with their activities in the
      individual manure treatment. Bacterial community tolerance to SDZ and CTC in
      manure-amended soil increased significantly (p?0.05) with antibiotic treatment
      frequency. 

PMID- 23948607
TI  - Resembling a "natural formation pattern" of chlorinated dibenzo-p-dioxins by
      varying the experimental conditions of hydrothermal carbonization.
AB  - Until several years ago dioxins were considered as just an unwanted by product of
      anthropogenic activities and stigmatized as the symbol of man-made environmental
      pollution. Natural processes, such as forest fires, can emit dioxins, but
      compared to industrial processes, usually very low quantities are emitted.
      However after a case of food contamination occurred in the United States of
      America in 1996 caused by kaolinitic clay a discussion on the provenience
      started. Besides the relatively high concentration also an unusual PCDD/F
      distribution pattern was found in these ball clay samples. This specific pattern
      related to none of the known anthropogenic sources for these contaminants and, in
      relation to a supposed natural formation, later it was named "natural formation
      pattern". Hydrothermal carbonization (HTC) can transform biomass within hours
      into a brown coal-like product which resembles naturally occurring coal
      formation. HTC can also transform an already present PCDD/F contamination in a
      way to obtain a "natural formation pattern" characterized by an unusual high
      ratio between 1,2,3,7,8,9-HxCDD and 1,2,3,6,7,8-HxCDD and the absence of almost
      all chlorinated dibenzofurans. By varying the experimental conditions of the HTC
      process applied to sewage sludge samples contaminated with PCDD/Fs from
      anthropogenic sources, beside the "natural formation pattern" at a temperatures
      of 255  degrees C, a remarkable increase of the toxicity based on WHO-TEQ was
      observed.

PMID- 23948609
TI  - Comment on "Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS)
      in surface waters, sediments, soils and wastewater--A review on concentrations
      and distribution coefficients" by Zareitalabad et al. [Chemosphere 91(6) (2013)
      725-732].

PMID- 23948608
TI  - Ecological bioavailability of permethrin and p,p'-DDT: toxicity depends on type
      of organic matter resource.
AB  - Hydrophobic organic contaminants readily partition from aqueous to organic phases
      in aquatic systems with past research largely focusing on sediment. However,
      within many aquatic systems, matrices such as leaf material and detritus are
      abundant and ecologically important, as they may represent a primary exposure
      route for aquatic invertebrates. The objectives of the present study were to
      examine partitioning and toxicity to Hyalella azteca among permethrin and p,p'
      DDT contaminated sediment, leaf, and a sediment-leaf mixture. Log organic carbon
      water partitioning coefficients ranged from 4.21 to 5.82 for both insecticides,
      and were greatest within sediment and lowest in coarse leaf material. H. azteca
      lethal concentrations for 50% of the population (LC50s) ranged from 0.5 to
      111MUgg(-1) organic carbon, and were dependent on the matrix composition. The
      variation in sorption and toxicity among matrices common within stream ecosystems
      suggests that the ecological niche of aquatic organisms may be important for
      estimating risk of hydrophobic pesticides. 

PMID- 23948610
TI  - Removal of dichloromethane from ground and wastewater: a review.
AB  - Dichloromethane (DCM) is a toxic volatile compound which is found in the ground
      waters and wastewaters of the pharmaceutical, chemical, textile, metal-working
      and petroleum industries. DCM inhibits the growth of aquatic organisms, induces
      cancer in animals and is potentially carcinogenic for humans. This article aims
      to review existing water treatments for DCM removal, focusing on recent
      technological advances. Air stripping, adsorption and pervaporation were found to
      be effective in separating DCM from water with a process efficiency of about 99%,
      90% and 80% respectively. Electrocatalysis over Cu-impregnated carbon fiber
      electrode, photo irradiation over TiO2 and photo-Fenton process led to the
      complete decomposition of DCM. Aerobic and anaerobic water treatment achieved 99%
      and 95% removal of DCM respectively. The maximum efficiencies observed for
      acoustic cavitation, radiolysis and catalytic degradation of CH2Cl2 were 90%, 92%
      and 99% respectively. Ozonation and persulfate oxidation showed lower DCM
      degradation efficiencies, not exceeding 20%. Further combination of different
      water treatment methods will further increase DCM degradation efficiency.

PMID- 23948611
TI  - Reactions of three halogenated organophosphorus flame retardants with reduced
      sulfur species.
AB  - Tris(haloalkyl)phosphates (THAPs) are among the most widely used flame retardants
      in the U.S. They have been identified as one of the most frequently detected
      contaminants in U.S. streams. These contaminants are of toxicological concern in
      sensitive coastal ecosystems such as estuaries and salt marshes. It is likely
      that reactions with reduced sulfur species such as polysulfides (Sn(2-)) and
      bisulfide (HS(-)), present in anoxic subregions of coastal water bodies could
      have a significant impact on rates of removal of such contaminants, especially
      since no significant degradation reactions in the environment (e.g., hydrolysis,
      biological degradation) is reported for these compounds. The kinetics of the
      reaction of reduced sulfur species with three structurally related THAPs have
      been determined in well-defined aqueous solutions under anoxic conditions.
      Reactions were monitored at varying concentrations of reduced sulfur species to
      obtain second-order rate constants from the observed pseudo-first order rate
      constants. The degradation products were studied with GC-FID and LC-MS. The
      reactivity of Sn(2-), thiophenolate, and HS(-) were compared and steric, as well
      as electronic factors are used to explain the relative reactivity of the three
      THAPs with these three sulfur species. 

PMID- 23948612
TI  - The OH-initiated atmospheric reaction mechanism and kinetics for levoglucosan
      emitted in biomass burning.
AB  - Levoglucosan is a typical molecular tracer of biomass-burning aerosols in the
      atmosphere. The mechanism for OH-initiated reaction with levoglucosan is studied
      at the level of MPWB1K/6-311+G(3df,2p)//MPWB1K/6-31+G(d,p). The possible
      subsequent reactions in the presence of O2, NO and H2O are also taken into
      consideration. The study shows that the H atom abstraction from the C4-position
      by the OH radical is an energetically favorable pathway, and that the OH
      initiated products contribute to the formation of SOA and atmospheric acidity.
      The kinetic calculation is performed and the rate constants are calculated over
      the temperature range of 200-1500 K, using the Rice-Ramsperger-Kassel-Marcus
      (RRKM) theory. The rate constant of levoglucosan reacting with the OH radical at
      298 K is 2.21*10(-13) cm(3) molecule(-1) s(-1) and the atmospheric lifetime is 26
      days ([OH]=2.0*10(6) molecule cm(-3)). The equilibrium constants both in gas
      phase and aqueous are computed. The free energy DeltaG indicates that, the
      subsequent reactions tend to take place more spontaneously once the reaction
      occurs. This work provides a comprehensive investigation about OH-initiated
      atmospheric reactions with levoglucosan, which is helpful for experiment and risk
      assessment.

PMID- 23948613
TI  - Impaired Th1 immunity in ovarian cancer patients is mediated by TNFR2+ Tregs
      within the tumor microenvironment.
AB  - Ovarian cancer is a prevalent gynecological malignancy with potent immune
      suppression capabilities; regulatory T cells (Tregs) are significant contributors
      to this immune-suppression. As ovarian cancer patients present with high levels
      of TNF and Tregs expressing TNFR2 are associated with maximal suppressive
      capacity, we investigated TNFR2+ Tregs within these patients. Indeed, TNFR2+
      Tregs from tumor-associated ascites were the most potent suppressor T cell
      fraction. They were abundantly present within the ascites and more suppressive
      than peripheral blood TNFR2+ Tregs in patients. The increased suppressive
      capacity can be explained by a distinct cell surface expression profile, which
      includes high levels of CD39, CD73, TGF-beta and GARP. Additionally, CD73
      expression level on TNFR2+ Tregs was inversely correlated with IFN-gamma
      production by effector T cells. This Treg fraction can be selectively recruited
      into the ascites from the peripheral blood of patients. Targeting TNFR2+ Tregs
      may offer new approaches to enhance the poor survival rates of ovarian cancer. 

PMID- 23948614
TI  - Surgical versus nonsurgical treatment of femur fractures in people with spinal
      cord injury: an administrative analysis of risks.
AB  - OBJECTIVE: To assess the risks associated with surgical and nonsurgical care of
      femur fractures in people with spinal cord injury (SCI). DESIGN: Retrospective
      cohort study; an analysis of Veterans Affairs (VA) data from the National Patient
      Care Database. SETTING: Administrative data from database. PARTICIPANTS: The
      cohort was identified by searching the administrative data from fiscal years 2001
      to 2006 for veterans with a femur fracture diagnosis using the International
      Classification of Diseases, 9th Revision, Clinical Modification codes. This group
      was subdivided into those with (n=396) and without (n=13,350) SCI and those
      treated with and without surgical intervention. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Rates of mortality and adverse events. RESULTS: The SCI
      group was younger with more distal fractures than the non-SCI group. In the non
      SCI population, 78% of patients had associated surgical codes compared with 37%
      in the SCI population. There was higher mortality in the non-SCI group treated
      nonoperatively. In the SCI population, there was no difference in mortality
      between patients treated nonoperatively and operatively. Overall adverse events
      were similar between groups except for pressure sores in the SCI population, of
      which the nonoperative group had 20% and the operative had 7%. Rates of surgical
      interventions for those with SCI varied greatly among VA institutions.
      CONCLUSIONS: We found lower rates of surgical intervention in the SCI population.
      Those with SCI who had surgery did not have increased mortality or adverse
      events. Surgical treatment minimizes the risks of immobilization and should be
      considered in appropriate SCI patients.

PMID- 23948615
TI  - It's a myth that protection against disease is a strong and general service of
      biodiversity conservation: Response to Ostfeld and Keesing.

PMID- 23948616
TI  - Community-acquired pneumonia team decreases length of stay in hospitalized, low
      risk patients with pneumonia.
AB  - BACKGROUND: Team-focused intervention to improve the care of low-risk patients
      with community-acquired pneumonia (CAP) is a matter of controversy. Our aim was
      to determine if a community-acquired pneumonia team (CAPT) would shorten hospital
      length of stay (LOS) and improve health care utilization in low-risk patients
      with CAP compared with management by a general pulmonary team (GPT). METHODS: We
      performed a prospective cohort study of hospitalized, low-risk patients with CAP
      (Pneumonia Severity Index [PSI] score class I or II) at a single tertiary
      hospital from June 2007 to June 2008. Study patients were stratified to
      management by the CAPT treating group (n = 35), following the Infectious Diseases
      Society of America (IDSA) and American Thoracic Society (ATS) CAP guideline
      recommendations, or to management by the GPT (n = 30) following the standard of
      care. Primary outcome measure for comparison of the efficacy of the 2 different
      team-focused interventions was hospital LOS for patients with CAP. Secondary
      study outcome measures included patient 30- and 90-day all-cause readmission
      rate, rate of mortality at 30 and 90 days, antibiotic-treatment duration, time to
      switch patient from intravenous (IV) to oral antibiotic treatment, and time to
      achieve clinical stability for patients. RESULTS: Hospitalized, low-risk patients
      with CAP, who were assisted by a CAPT were more likely to have a shorter hospital
      stay (9 days less; P < 0.001), shorter time to switch from IV to oral antibiotic
      therapy (8 days less; P <0.001), and total shorter duration of antibiotic
      treatment (6 days less; P <0.001), when compared with low-risk patients with CAP
      who were assisted by a GPT. In addition, for both groups of assisted patients,
      there were no differences in the time to achieve clinical stability, use of
      guideline-concordant antibiotic therapy, rate of mortality, or rate of
      readmissions at 30 and 90 days. CONCLUSIONS: Management by a dedicated CAPT
      reduced patient hospital LOS, time to switch from IV to oral antibiotic therapy,
      and duration of antibiotic treatment, without causing adverse events, compared
      with standard of care, in low-risk patients with CAP.

PMID- 23948617
TI  - Longer in-hospital wait times do not result in worse outcomes for patients
      requiring urgent coronary artery bypass graft surgery.
AB  - BACKGROUND: In certain health care systems, patients wait for non-emergency
      services. Although waiting may not be considered acceptable, the delay may allow
      for patient optimization, such as giving time for "toxic" agents to be cleared,
      that could improve outcomes. We sought to determine the relationship between wait
      times and outcomes in in-hospital patients undergoing urgent coronary artery
      bypass graft (CABG) surgery. METHODS AND RESULTS: A prospectively collected
      database of consecutive, medically urgent, but clinically stable patients
      undergoing CABG surgery from 1995 to 2007, was analyzed. A total of 3067 patients
      with need for urgent CABG surgery with various in-hospital wait times (n = 440, 0
      2 days; n = 799, 3-5 days; n = 1317, 6-10 days; n = 511, 11-15 days) were
      included. There were no differences in mortality, intensive care unit (ICU) or
      post-surgery hospital length of stay (LOS) among the patient groups. Multivariate
      logistic regression analysis revealed that wait time was not associated with
      mortality (P = 0.625). Due to changes in the nonsurgical management of coronary
      artery disease, a separate analysis of patients, from 2002 to 2007, was also
      performed to explore contemporary results. In the latter subset, 1495 patients (n
      = 175, 341, 720, 259, in the same 4 respective wait-time groups) were included;
      the 0-2 days patient group underwent more blood transfusions (50% vs 38%; P =
      0.01), prolonged ventilation (6% vs 2%; P = 0.05), post-operative dialysis (2% vs
      0%; P = 0.08), and longer ICU LOS (26 vs 23 hours; P = 0.02) compared with the 3
      5 days patient group. The Society of Thoracic Surgeons mortality risk scores of
      the 0-2 days and 3-5 days groups were the same (1.5%). Multivariate regression
      analysis revealed that increased wait time was associated with fewer patients
      requiring blood transfusion (P < 0.05) for CABG surgery. CONCLUSION: Waiting for
      in-hospital urgent CABG surgery does not lead to worse patient outcomes and may,
      in fact, reduce the procedural and medical risks of postoperative blood
      transfusions, prolonged ventilation, dialysis, and shorten ICU LOS.

PMID- 23948618
TI  - Poor positive predictive value of McConnell's sign on transthoracic
      echocardiography for the diagnosis of acute pulmonary embolism.
AB  - BACKGROUND: Acute pulmonary embolism (PE) is a life-threatening condition. Making
      a definitive diagnosis with radiologic studies may delay therapy or be unsafe for
      the patient. Echocardiography is readily available and can suggest PE by
      demonstrating right ventricular (RV) dysfunction. McConnell's sign on
      echocardiogram (ECHO-CG) (RV dysfunction with characteristic sparing of the apex)
      has been reported to have high sensitivity and specificity for the diagnosis of
      acute PE. It is hypothesized that McConnell's sign on ECHO-CG in patients
      hospitalized with suspected acute PE would have a high positive predictive value
      (PPV). METHODS: Data, from 2005 to 2010, were retrospectively collected on all
      patients with an ECHO-CG interpreted as revealing McConnell's sign, who had
      undergone another diagnostic study (computed tomography pulmonary angiography,
      ventilation-perfusion scan, upper or lower extremity Doppler ultrasound, or
      autopsy) for venous thromboembolic disease (VTE). The PPV on transthoracic ECHO
      CG was calculated for the diagnostic accuracy of McConnell's sign in all
      patients. To minimize the potential for ECHO-CG reader bias of patients already
      confirmed to have had a PE by another modality, the PPV was then recalculated
      only on the patients in whom the ECHO-GM was the first diagnostic study. RESULTS:
      Seventy-three patients had findings of McConnell's sign on ECHO-CG. The PPV of
      McConnell's sign on ECHO-CG was 57% (CI, 45%-67%). Of the 37 patients who
      underwent an ECHO-CG in the first study for suspected acute PE, 15 patients had
      VTE confirmed; the PPV in this subset was only 40% (CI, 24%-56%). There were 20
      patient deaths overall; of these, only 9 of the patients were confirmed to have
      VTE. CONCLUSION: We concluded that the presence of McConnell's sign has a
      relatively poor PPV for the diagnosis of acute PE and should not be used in
      isolation when making a diagnosis of PE in patients.

PMID- 23948619
TI  - Diagnosis and treatment of pneumothorax.
AB  - Many diagnostic and therapeutic options exist for the evaluation and treatment of
      patients with pneumothorax. Guidelines from US and European professional
      societies and individual expert opinions differ in the approach to patient care.
      Advances in diagnostic techniques, such as real-time thoracic ultrasound, have
      added to the evaluation strategy. It is important for medical trainees and
      providers to become familiar with techniques utilized worldwide as they may be
      encountered in clinical practice. We review current evidence, expert
      recommendations, and compare professional society guidelines discussing the
      various diagnostic and management options for patients with pneumothorax to
      assist physicians and trainees involved in the care of hospitalized and
      outpatient adults who have primary, secondary, and traumatic iatrogenic
      pneumothorax. Management of traumatic non-iatrogenic pneumothorax is beyond the
      scope of this article, thus, not reviewed here. 

PMID- 23948620
TI  - Improving rates of intermittent pneumatic compression therapy utilization.
AB  - BACKGROUND: The most preventable causes of death in the hospitalized patient are
      deep vein thrombosis (DVT) and pulmonary embolism. Despite the long-term (> 15
      years) availability of evidence-based consensus guidelines for prevention of
      venous thromboembolism, thromboprophylaxis remains underused. Improving staff and
      patient utilization of prophylactic treatment for postoperative patients reduces
      hospital-acquired venous thromboembolism and improves patient outcomes. Anecdotal
      evidence and observations of intermittent pneumatic compression (IPC) therapy
      utilization at the authors' institution suggested that ordered IPC therapy was
      not consistently in use with postsurgical patients. OBJECTIVES: We sought to
      increase the use of IPC devices by all staff on our hospital pilot units and to
      promote sustained use of IPC devices. METHODS: Multiple methodologies were
      employed to address this issue, including point prevalence audits, root-cause
      analyses, a nursing survey, and a pilot project on selected surgical units.
      RESULTS: Statistically significant improvements on the pilot units were achieved
      by implementing a 3-tier interventional plan. CONCLUSION: Our pilot project
      demonstrated that nurse education, patient education, and nurse attention to
      solving systems issues can significantly improve IPC use in surgical patients.

PMID- 23948621
TI  - Update on management of patients with overt hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) is a multifactorial neuropsychiatric disease that
      affects patients with cirrhosis. We review the clinical impact, pathogenesis,
      evaluation, management, and prevention of overt HE in patients with cirrhosis.
      Articles published between January 1960 and November 2012 were acquired through a
      MEDLINE search of different combinations of the terms hepatic encephalopathy,
      pathophysiology, treatment, prophylaxis, prevention, prognosis, and recurrence.
      The Healthcare Cost and Utilization Project database was used to obtain
      prevalence and cost information related to hospitalizations of patients with HE.
      The literature describes significant morbidity and mortality of HE in patients
      with cirrhosis. Overt HE develops in 30% to 45% of patients with cirrhosis and is
      associated with a substantial pharmacoeconomic burden, particularly HE-related
      hospitalizations. The development of HE in patients with cirrhosis portends a
      worsened prognosis and is incorporated into the Child-Pugh classification of the
      severity of liver disease. In the hospitalized patient, the development of HE is
      associated with precipitating events (eg, gastrointestinal bleeding, dehydration,
      infection), and in some patients, its course is characterized by frequent and
      severe relapses. In addition, hospitalized patients with overt HE have a 3.9-fold
      increased mortality risk. Patient management employs nonabsorbable disaccharides,
      the nonsystemic antibiotic rifaximin, or both, to treat acute HE episodes and
      prevent HE relapse. In open-label trials, use of the nonabsorbable disaccharide
      lactulose reduced the risk of overt HE recurrence in patients compared with no
      lactulose control groups for <= a median of 14 months. In a randomized, placebo
      controlled trial, rifaximin 550 mg twice daily was more effective in maintaining
      HE remission compared with placebo and was associated with a reduction in HE
      related hospitalizations. Recent advances in treatment and preventative therapies
      may reduce the personal, societal, and economic impact of this disorder. 

PMID- 23948622
TI  - A review of venous thromboembolism prophylaxis for hospitalized medical patients.
AB  - In the last decade, greater focus has been directed toward venous thromboembolism
      (VTE) prophylaxis in hospitalized, non-surgical patients. Both deep venous
      thrombosis and pulmonary embolism are potentially preventable causes of patient
      morbidity and mortality related to hospitalization. Despite the availability of
      high-quality, evidence-based guidelines for VTE prevention, there is compelling
      evidence that many hospitalized patients do not receive appropriate VTE
      prevention measures. Hospitalists play an important role in the implementation of
      appropriate VTE prophylaxis measures for this patient population; thus, knowledge
      of updated recommendations is vital to their practice, as well as patient safety.
      We provide a comprehensive evidence-based clinical review of VTE prophylaxis for
      nonsurgical hospitalized patients, including risk factors and risk assessment,
      indications for prophylaxis, recommended therapeutic options, and updates from
      recently released practice guidelines by the American College of Physicians and
      the American College of Chest Physicians, published in 2011 and 2012,
      respectively. 

PMID- 23948623
TI  - Utility of a post-hospitalization stroke prevention program managed by nurses.
AB  - GOAL: Evidence-based guidelines exist for the prevention and treatment of
      patients with cerebral ischemia. Despite these guidelines, there are gaps in
      clinical practice. Our study aimed to determine if a physician-directed, nurse
      case-management program could reduce individual patient vascular risk factors.
      METHODS: Patients hospitalized with atherosclerotic cerebral ischemia with >= 1
      major uncontrolled risk factor for stroke (hypertension, tobacco use,
      dyslipidemia, diabetes) were eligible to enroll in our study. Patients were
      randomized to management by the nurse-prevention program or usual care. Patients
      in the usual-care group received their initial risk-factor assessment and a
      scheduled follow-up at 1 year. Patients in the usual-care group underwent further
      follow-up by primary care and/or neurology as recommended during their
      hospitalization or outpatient visit. Patients assigned to the prevention group
      received individualized education, motivational interviewing, and were aided in
      setting up their risk-factor modification goal plan. Additional education was
      tailored to each patient based on individualized risk factors. Prevention-group
      patients also underwent consultation with a registered dietitian and an exercise
      physiologist. The primary endpoint of the study was improvement of >= 1 major
      patient risk factor for occurrence of stroke to goal at 1 year. RESULTS: At 1
      year post-hospitalization, patients in the nurse-care-management group were 42%
      more likely to have met the primary endpoint (n = 18; 61% nurse-managed patients)
      compared with 33% (n = 18) of patients undergoing usual care (P = 0.09). There
      was no significant reduction in minor risk factors for either patient group.
      Patients in the prevention group had greater reductions in low-density
      lipoprotein cholesterol levels (-38 vs -4; P = 0.0083), changes in cardiovascular
      risk score (-5.2 vs 1.3; P = 0.0033), and had a greater reductions in systolic
      blood pressure (-12.2 vs -0.105; P = 0.07) than their usual-care counterparts
      (changes shown respectively). Patients in the prevention group were more likely
      to follow a prescribed diet than those in the usual-care group (50% vs 7%,
      respectively; P = 0.0070) and maintain an exercise program (83% vs 33%,
      respectively; P = 0.0018). SUMMARY: A physician-directed, nurse case-management
      system for patients post-hospitalization for cerebral ischemia is feasible and
      may help improve long-term control of major patient risk factors for stroke. A
      larger trial is needed to verify trends noted in our study.

PMID- 23948624
TI  - The surgical scorecard: a tool to close the loop on OR utilization.
AB  - OBJECTIVE: Operating room (OR) suites are among the highest cost- and highest
      revenue-generating areas in most hospitals. A scorecard containing utilization
      and performance metrics for each surgical service and surgeon was designed by the
      OR leadership with results sent monthly to each surgical chief. Recent trends
      reveal an increased focus on optimizing utilization of OR resources as part of
      institutional cost-analysis efforts. Protected block time into which elective
      surgical and procedural cases can be booked must be used appropriately and booked
      fully to offset the fixed costs of staffing and running the OR. DESIGN AND
      SETTING: The intent of the scorecard tool was to provide detailed information on
      utilization of protected block time for performance-improvement planning. First
      case on-time start was also measured and reported so that block time at the start
      of the day was fully utilized. With the granular information on time-use
      performance of each surgeon, the surgical chiefs were able to make workflow
      changes to improve utilization of staffed prime-time block hours. The scorecard
      tool is used ultimately for communication, not calculation, of utilization
      metrics. MEASUREMENTS AND CONCLUSIONS: Block-time utilization was measured both
      before and after the implementation of the scorecard. The analysis of the period
      before and after implementation of the scorecard revealed an improvement in block
      time utilization in all but 1 surgical service.

PMID- 23948625
TI  - Management of the hospitalized patient with type 1 diabetes mellitus.
AB  - Patients with type 1 diabetes mellitus (T1DM) have minimal to absent pancreatic
      beta-cell function and rely on the exogenous delivery of insulin to obtain
      adequate and life-sustaining glucose homeostasis. Maintaining glycemic control is
      challenging in hospitalized patients with T1DM, as insulin requirements are
      influenced by the presence of acute medical or surgical conditions, as well as
      altered nutritional intake. The risks of hyperglycemia, ketoacidosis,
      hypoglycemia, and glycemic variability are increased in hospitalized patients
      with T1DM. Diabetic ketoacidosis and severe hypoglycemia are the 2 most common
      emergency conditions that account for the majority of hospital admissions in
      patients with T1DM. The association between hyperglycemia and increased risk of
      complications and mortality in patients with type 2 diabetes (T2DM) is well
      established; however, the impact of glycemic control on clinical outcomes has not
      been determined in patients with T1DM who present without ketoacidosis. To
      decrease complications associated with insulin therapy, health care professionals
      must be well versed in the use of insulin because it is a common source of
      medication error. For non-critically ill, hospitalized patients, subcutaneous
      insulin given to cover basal and prandial needs instead of sliding scale is the
      preferred method of insulin dosing. Protocols are available for initiating and
      titrating insulin doses, as well as for transitioning from an insulin infusion to
      a subcutaneous regimen. In our review, we identify and discuss special
      considerations related to inpatient glycemic control of non-ketotic patients with
      T1DM. Additionally, point differences and similarities associated with the
      management of patients with T2DM are discussed. 

PMID- 23948626
TI  - Lithium-associated hyperthyroidism.
AB  - Goiters and hypothyroidism are well-known patient complications of the use of
      lithium for treatment of bipolar disease. However, the occurrence of lithium
      induced hyperthyroidism is a more rare event. Many times, the condition can be
      confused with a flare of mania. Monitoring through serial biochemical measurement
      of thyroid function is critical in patients taking lithium. Hyperthyroidism
      induced by lithium is a condition that generally can be controlled medically
      without the patient having to discontinue lithium therapy, although in some
      circumstances, discontinuation of lithium therapy may be indicated. We report on
      a patient case of lithium-associated hyperthyroidism that resolved after
      discontinuation of the medication. 

PMID- 23948627
TI  - To see or not to see: imaging surfactant coated nano-particles using HIM and SEM.
AB  - Nano-particles are of great interest in fundamental and applied research.
      However, their accurate visualization is often difficult and the interpretation
      of the obtained images can be complicated. We present a comparative scanning
      electron microscopy and helium ion microscopy study of cetyltrimethylammonium
      bromide (CTAB) coated gold nano-rods. Using both methods we show how the gold
      core as well as the surrounding thin CTAB shell can selectively be visualized.
      This allows for a quantitative determination of the dimensions of the gold core
      or the CTAB shell. The obtained CTAB shell thickness of 1.0 nm-1.5 nm is in
      excellent agreement with earlier results using more demanding and reciprocal
      space techniques.

PMID- 23948628
TI  - Causes of elevated D-dimer in patients admitted to a large urban emergency
      department.
AB  - BACKGROUND: Although the request for D-dimer is widespread in emergency
      departments (EDs), the causes of elevation and their relationship with D-dimer
      levels in patients with diagnostic values are uncertain. METHODS: In this
      retrospective investigation, the study population consisted of all patients who
      visited our large urban ED in the year 2012, for whom a D-dimer test was
      requested for excluding or diagnosing venous thromboembolism (VTE). Only patients
      with D-dimer values >243ng/mL were included, regardless of their pre-test
      clinical probability for VTE. RESULTS: The final study population consisted of
      1647 patients. A significant positive correlation was found between age and D
      dimer. Infection was the most frequent diagnosis (15.6%), followed by VTE
      (12.1%), syncope (9.4%), heart failure (8.9%), trauma (8.2%) and cancer (5.8%). D
      dimer was higher in patients with VTE than in those with other diagnoses
      (2541ng/mL vs 1030ng/mL; p<0.001). The frequency of VTE gradually increased from
      patients with values <1000ng/mL to those with D-dimer >3000ng/mL (4.1 vs 26.7%;
      p<0.001). As compared with D-dimer values <1000ng/mL, the Odds Ratio for VTE was
      8.5 for values >3000ng/mL. CONCLUSIONS: These results show that D-dimer lacks
      specificity for diagnosing VTE, especially in elderly patients admitted to the ED
      with significant co-morbidities. In older patients, elevated values (>1000ng/mL)
      are more frequently associated with VTE, so the use of higher cut-offs may be
      advantageous.

PMID- 23948629
TI  - Neural response to emotional stimuli associated with successful antidepressant
      treatment and behavioral activation.
AB  - BACKGROUND: Major Depressive Disorder (MDD) is a leading cause of disability
      globally. Currently available treatments have limited efficacy and combination
      strategies are frequently used. Several lines of research have demonstrated that
      MDD patients experience impairments in various components of affective
      processing, including regulation of affective states. AIM: To identify baseline
      and 1-week neuroimaging predictors of response to a 6-week trial of
      fluoxetine/olanzapine combination treatment during an affective processing task.
      METHODS: Twenty-one MDD patients and 18 healthy controls were enrolled in the
      study. MDD patients were treated for 6 weeks with fluoxetine (40-60 mg/day) and
      olanzapine (5-12.5mg/day). All participants viewed images from the International
      Affective Picture Rating System during a functional magnetic resonance (fMRI)
      scan at baseline and 1 week. RESULTS: There was a 57% response rate (defined as a
      50% decrease in Hamilton Rating Scale for Depression-17 item) at 6 weeks. At
      baseline, responders had increased premotor activity while viewing negative
      images compared to non-responders and healthy controls. Higher baseline premotor
      activity was also predictive of greater percent change on the HAMD-17 and
      improvement in negative disposition and behavioral drive. Non-responders
      exhibited increased insular activity at baseline compared to responders. Higher
      activity in the posterior cingulate cortex was also predictive of greater percent
      change on the HAMD-17. Change from baseline to 1 week did not produce any
      significant predictive findings. CONCLUSIONS: Treatment with
      fluoxetine/olanzapine demonstrated similar biomarkers of response to
      monotherapeutic strategies. In particular, posterior cingulate cortex, anterior
      insula, and premotor cortex may show predictive differences in their response to
      affective images prior to treatment. Further research needs to be conducted to
      determine the utility of early changes in emotion circuitry in predicting
      antidepressant response.

PMID- 23948630
TI  - Mauling of the "Celtic Tiger": clinical characteristics and outcome of first
      episode depression secondary to the economic recession in Ireland.
AB  - BACKGROUND: There is a dearth of studies describing clinical characteristics and
      outcome of patients who present with mood disorders related to economic
      recession. AIMS: To describe a cohort of patients admitted with first-episode
      depression related to the Irish economic recession and compare this cohort with
      all other first-episode depressives admitted during the same time period (2009
      2010). METHODS: A cohort of 137 patients admitted with first-episode depression
      to an independent university teaching hospital was prospectively identified and
      followed up from admission over 2 years (mean follow-up 430 days, s.d. 176 days).
      The cohort was divided into "Celtic Tiger" (patients with first-episode
      depression secondary to the economic recession) and non-Celtic Tiger control
      patients (other first-episode depressed patients). Both groups were compared in
      terms of clinical characteristics at baseline and outcome over follow-up.
      RESULTS: The number of admissions due to first depressive episodes were higher in
      recession years 2009/10 than in pre-recession years 2008/9. Celtic Tiger patients
      were predominantly male and more severely depressed with more marked suicidal
      ideation (chi(2), p<0.001) than control patients. They were more likely to
      recover (chi(2), p=0.013), less likely to recur (chi(2), p<0.001) and had faster
      time to recovery (log rank, p<0.001) and slower time to full recurrence (log
      rank, p=0.001). The Celtic Tiger patients spent more time asymptomatic and less
      time at full and subthreshold depression levels over follow-up. LIMITATIONS:
      Study setting of centre specializing in affective disorders treatment,
      retrospective nature of follow-up after initial prospective interview and lack of
      patient follow-up interview. CONCLUSION: The study describes a subgroup of
      patients with severe depression associated with economic recession with likely
      high suicide risk but very favourable outcome.

PMID- 23948633
TI  - Inefficiency of emotion regulation as vulnerability marker for bipolar disorder:
      evidence from healthy individuals with hypomanic personality.
AB  - OBJECTIVE: Emotion regulation deficits are a key characteristic of bipolar
      disorder (BD). In the present study, we asked if deficits in emotion regulation
      are also a vulnerability marker for BD. To this end, we investigated a healthy
      group of participants at high-risk for developing BD, defined on the basis of a
      hypomanic personality trait. We examined the neural correlates of two emotion
      regulation strategies, reappraisal and distraction. METHOD: Twenty-two
      individuals with higher risk for BD and twenty-four controls were investigated in
      a functional magnetic resonance imaging paradigm. Participants were presented
      with negative, positive and neutral pictures and were either required to
      passively view the images, to down-regulate the emotional response by
      reappraising the pictures' content, or to perform a distracting arithmetic task.
      RESULTS: High-risk individuals showed increased emotional reactivity to negative
      stimuli, indicated by heightened amygdala activation during passive viewing. High
      risk participants were also less successful in down-regulating amygdala activity
      using reappraisal of negative stimuli. During distraction from positive stimuli,
      high-risk individuals showed heightened task-related activity in the inferior
      parietal cortex, suggesting increased distractibility by task-irrelevant positive
      background stimuli. There were no differences in habitual emotion regulation as
      assessed by a self-report questionnaire. LIMITATIONS: Generalizability of the
      present results is limited by the age- and education-homogenous sample and the
      small sample size. CONCLUSIONS: This is the first study to report neural
      correlates of increased emotional reactivity and deficient emotion regulation in
      healthy individuals at risk for BD. These findings suggest inefficient emotion
      regulation through reappraisal and distraction in individuals with high hypomanic
      personality who are supposed to be at higher risk to develop bipolar disorder.

PMID- 23948631
TI  - Depression and mortality: artifact of measurement and analysis?
AB  - BACKGROUND: Previous research demonstrates various associations between
      depression, cardiovascular disease (CVD) incidence and mortality, possibly as a
      result of the different methodologies used to measure depression and analyse
      relationships. This analysis investigated the association between depression, CVD
      incidence (CVDI) and mortality from CVD (MCVD), smoking related conditions
      (MSRC), and all causes (MALL), in a sample data set, where depression was
      measured using items from a validated questionnaire and using items derived from
      the factor analysis of a larger questionnaire, and analyses were conducted based
      on continuous data and grouped data. METHODS: Data from the PRIME Study (N=9798
      men) on depression and 10-year CVD incidence and mortality were analysed using
      Cox proportional hazards models. RESULTS: Using continuous data, both measures of
      depression resulted in the emergence of positive associations between depression
      and mortality (MCVD, MSRC, MALL). Using grouped data, however, associations
      between a validated measure of depression and MCVD, and between a measure of
      depression derived from factor analysis and all measures of mortality were lost.
      LIMITATIONS: Low levels of depression, low numbers of individuals with high
      depression and low numbers of outcome events may limit these analyses, but levels
      are usual for the population studied. CONCLUSIONS: These data demonstrate a
      possible association between depression and mortality but detecting this
      association is dependent on the measurement used and method of analysis.
      Different findings based on methodology present clear problems for the
      elucidation and determination of relationships. The differences here argue for
      the use of validated scales where possible and suggest against over-reduction via
      factor analysis and grouping.

PMID- 23948632
TI  - Depression with psychotic features is influenced by the polymorphism of the
      serotonin transporter gene.
AB  - INTRODUCTION: Current diagnostic classifications regard psychotic symptoms during
      depressive episodes as indicators of depression severity. However, growing
      evidence suggests that depression with psychotic symptoms (MDP) may represent a
      distinct subtype of depression. In the course of the search for discriminating
      factors we tested the hypothesis that the serotonin transporter gene (5-HTTLPR)
      may interact with the manifestation of psychotic symptoms in acute depression.
      METHODS: 112 inpatients (61 female) with a depressive episode (16 bipolar, 86
      unipolar) at admission were genotyped for 5-HTTLPR variants. Psychotic symptoms
      und general psychopathology were evaluated comprehensively using the Manual of
      the Association for Methodology and Documentation in Psychiatry
      (Arbeitsgemeinschaft fur Methodik und Dokumentation in der Psychiatrie, 1981).
      For statistical analysis a chi-square test and a logistic regression model was
      used. RESULTS: 16 (14.3%) out of 112 patients were currently presenting with
      psychotic symptoms. The primary finding of our study was the higher prevalence of
      the s-allele of the 5-HTTLPR within the group of MDP patients (Pearson chi2=7.87;
      df=2; p<0.03). Secondly, in a logistic regression model, 5-HTTLPR was found to
      significantly contribute to the diagnosis of MDP (chi2=6.5; df=1; p=0.01). This
      effect was even more pronounced upon comparing only severely depressed patients
      with MDP patients. From a psychopathological perspective, MDP patients showed
      higher AMDP hostility and apathy scores but equal AMDP depression scores.
      DISCUSSION: This is the first study to show an influence of 5-HTTLPR on psychotic
      symptoms in acutely depressed patients. LIMITATIONS: The lack of a control group
      and the relatively small sample size limits the present study's findings, thus
      replication in a larger sample is necessary.

PMID- 23948634
TI  - Identification of altered dipeptidyl-peptidase activities as potential biomarkers
      for unipolar depression.
AB  - BACKGROUND: Changes in circulatory aminopeptidases [dipeptidyl-peptidase-IV (DPP
      IV), Prolyl-oligopeptidase (POP) and Leucine aminopeptidase (LAP)] activities
      have been found to be associated with psychiatric illnesses and inflammatory
      diseases. METHODS: The discriminatory indices of aminopeptidases activities were
      assessed by enzymatic assays in plasma samples from 240 unipolar depression (UD)
      patients and 264 matched controls. In addition the relationship between soluble
      and cellular DPP-IV activity was determined in plasma and blood cells from
      healthy subjects. RESULTS: Greater than 95% of the plasma DPP-IV activity could
      be blocked by inhibitors, demonstrating the specificity of the assay. Also, DPP
      IV protein and activity levels were strongly correlated. In contrast, only 50% of
      the membrane-bound activity in blood cells was inhibited, which suggested that
      other similar peptidases may be present in these cells. UD patients had decreased
      plasma levels of DPP-IV and POP activities compared to healthy controls with a
      concomitant increase in LAP activity. Finally, testing of the LAP/DPP-IV ratio
      resulted in good discrimination of UD patients from controls with an area under
      the curve-receiver operating characteristic of 0.70. LIMITATIONS: Further
      biological validation studies using different cohorts are warranted. CONCLUSIONS:
      The finding that plasma DPP-IV activity was decreased and LAP activity was
      increased in UD patients suggests the potential value for testing the levels of
      these enzymes for improved classification of patients. In addition, the changes
      in these enzymes, suggests that the proteolytic maturation of their
      proneuropeptide and prohormone subtrates may also be affected in UD, resulting in
      altered production of the associated bioactive peptides.

PMID- 23948635
TI  - Suicide risk in the elderly: data from Brazilian public health care program.
AB  - OBJECTIVE: Examine prevalence and level of suicide risk, and its associations
      with sociodemographic factors and mood disorders. METHODS: A cross-sectional
      study with a random sample of 530 individuals aged 60 years or more from Family
      Health Strategy of Porto Alegre, Brazil. Diagnosis was made by psychiatrists
      using the Mini International Neuropsychiatric Interview plus (MINIplus). RESULTS:
      Suicide risk was found in 15.7% of the sample. Female gender, elderly with no
      income or with no paid activity and those who have lost one or more of his sons
      presented association with suicide risk. Bipolar disorder shows association with
      suicide risk for those with or without current episode. For unipolar depression
      only elderly with a current episode shows association with suicide risk.
      LIMITATIONS: The cross-sectional design limits the examination of causative
      relationships. The MINIplus questions are not broad enough to assess other
      important self-destructive behaviors. CONCLUSIONS: A high rate of suicide risk
      was found. As expected an increased rate of mood disorders were related to the
      risk of suicide. The loss of sons may partly explain a subtype of late-life risk
      of suicide or mood disorders especially in the oldest-old. These findings can be
      a useful to generate other research hypothesis and for health professionals who
      care older persons. Detecting characteristics linked to suicide, therefore
      opening up the possibility of preventing tragic outcomes providing a proper
      treatment.

PMID- 23948636
TI  - Effect of television viewing on social-emotional competence of young Thai
      children.
AB  - Exposure time, program content and cultural context may affect the impact of
      television (TV) on the social-emotional competence (SEC) of children. This study
      examined the effects of TV viewing on the SEC of Thai infants. The study was
      based on a Thai birth cohort study from which duration and content of TV viewing
      and data from the Modified Infant-Toddler Social and Emotional Assessment
      instrument at 1 and 3 years of age were available. Generalized estimating
      equations were used to examine whether scores below the 10th national percentile
      were associated with TV viewing duration. The relationship between viewing
      duration and SEC risk was quadratic rather than linear. Viewing duration of 30
      120 min/day was associated with a decreased risk of low overall SEC compared to
      non-viewers after adjustments for confounding factors. However, the beneficial
      effect diminished when the duration exceeded 120 min/day. Viewing educational
      programs was associated with a risk reduction of having low overall SEC compared
      to non-educational programs. These results suggest that a short period of TV
      viewing may be beneficial for the SEC of Thai infants, especially if the programs
      are educational.

PMID- 23948637
TI  - Can early improvement be an indicator of treatment response in obsessive
      compulsive disorder? Implications for early-treatment decision-making.
AB  - In major depression, early response to treatment has been strongly associated
      with final outcome. We aimed to investigate the ability of early improvement (4
      weeks) to predict treatment response at 12 weeks in DSM-IV-defined obsessive
      compulsive disorder (OCD) patients treated with serotonin reuptake inhibitors
      (SRI). We conducted an SRI practical trial with 128 subjects. INCLUSION CRITERIA:
      age range 18-65 years-old, baseline Yale-Brown Obsessive-Compulsive Scale (Y
      BOCS) score >= 16, and absence of previous adequate pharmacological treatment.
      Systematic assessments were performed at baseline, 4 and 12 weeks of treatment.
      Treatment response at 12 weeks was defined as a 35% or greater reduction in
      baseline Y-BOCS score. Stepwise logistic regression was used to test the
      relationship between early improvement and treatment response at 12 weeks, taking
      into account additional potential predictive factors. Different thresholds of
      early improvement were tested and their predictive power was calculated. Early
      improvement, defined as a 20% or greater reduction from baseline Y-BOCS score at
      4 weeks, predicted response at 12 weeks with 75.6% sensitivity and 61.9%
      specificity. According to a logistic regression including demographic and
      clinical features as explaining variables, early improvement was the best
      predictor of treatment response (OR = 1.05, p < 0.0001). Only 19.8% of patients
      who did not improve at 4 weeks were responders after 12 weeks. In contrast, 55.3%
      of the individuals who showed early improvement were responders at 12 weeks
      (Pearson Chi-Square = 17.06, p < 0.001). Early improvement predicted OCD
      treatment response with relatively good sensitivity and specificity, such that
      its role in early decision-making warrants further investigation in wider
      samples. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00680602.

PMID- 23948638
TI  - Glucocorticoid receptor gene expression and promoter CpG modifications throughout
      the human brain.
AB  - Glucocorticoids and the glucocorticoid (GR) and mineralocorticoid (MR) receptors
      have been implicated in many processes, particularly in negative feedback
      regulation of the hypothalamic-pituitary-adrenal axis. Epigenetically programmed
      GR alternative promoter usage underlies transcriptional control of GR levels,
      generation of GR 3' splice variants, and the overall GC response in the brain. No
      detailed analysis of GR first exons or GR transcript variants throughout the
      human brain has been reported. Therefore we investigated post mortem tissues from
      28 brain regions of 5 individuals. GR first exons were expressed throughout the
      healthy human brain with no region-specific usage patterns. First exon levels
      were highly inter-correlated suggesting that they are co-regulated. GR 3' splice
      variants (GRalpha and GR-P) were equally distributed in all regions, and GRbeta
      expression was always low. GR/MR ratios showed significant differences between
      the 28 tissues with the highest ratio in the pituitary gland. Modification levels
      of individual CpG dinucleotides, including 5-mC and 5-hmC, in promoters 1D, 1E,
      1F, and 1H were low, and diffusely clustered; despite significant heterogeneity
      between the donors. In agreement with this clustering, sum modification levels
      rather than individual CpG modifications correlated with GR expression. Two-way
      ANOVA showed that this sum modification was both promoter and brain region
      specific, but that there was however no promoter*tissue interaction. The
      heterogeneity between donors may however hide such an interaction. In both
      promoters 1F and 1H modification levels correlated with GRalpha expression
      suggesting that 5-mC and 5-hmC play an important role in fine tuning GR
      expression levels throughout the brain. 

PMID- 23948639
TI  - Loss of MeCP2 function is associated with distinct gene expression changes in the
      striatum.
AB  - Rett syndrome (RTT) is a neurodevelopmental disorder characterized by
      developmental regression beginning 6-18months after birth, followed by a lifetime
      of intellectual disability, stereotyped behaviors, and motor deficits. RTT is
      caused by mutations in the gene encoding MeCP2, a methyl-CpG binding protein
      believed to modulate gene transcription. Gene expression studies of individual
      brain regions have reported that Mecp2 loss-of-function leads to both activation
      and repression of its gene targets in mice. Conditional deletion of MeCP2 from
      different brain regions has revealed unique insights into the role of these
      structures in mediating particular RTT-like phenotypes. However, the function of
      MeCP2 in the striatum, a major brain region involved in motor control and
      executive cognitive functions, has yet to be studied. Here, we characterized the
      gene expression changes in the striatum of Mecp2 mutant mice. We found a number
      of differentially expressed genes in the striatum of both constitutive Mecp2-null
      mice and mice lacking MeCP2 only from forebrain GABAergic neurons. These changes
      only occurred when MeCP2 expression levels had reached mature levels and RTT-like
      symptoms were manifest, supporting a role for MeCP2 in maintaining proper brain
      function. Many of the gene expression changes identified in the striatum have not
      previously been shown to change in the hypothalamus or cerebellum. Bioinformatic
      analysis of differentially expressed genes in striatum as well as hypothalamus
      and cerebellum revealed that loss of MeCP2 does not affect the global landscape
      of gene expression. Additionally, we uncovered a number of differentially
      expressed genes in the liver of Mecp2-null mice suggesting an important role for
      MeCP2 in non-neuronal tissues. Collectively, our data suggest that the
      differential expression of genes following loss of MeCP2 occurs in a tissue- or
      cell-type specific manner and thus MeCP2 function should be understood in a
      cellular context. 

PMID- 23948640
TI  - Combined therapy with cyclodextrin/allopregnanolone and miglustat improves motor
      but not cognitive functions in Niemann-Pick Type C1 mice.
AB  - Niemann-Pick Type C1 (NPC1) is an autosomal recessive disorder characterized by
      the accumulation of cholesterol and glycosphingolipids. Combination-treatment
      utilizing cyclodextrin, allopregnanolone and miglustat (CYCLO/ALLO/miglustat) can
      ameliorate NPC1 disease in a mutant mouse model. The present study was designed
      to add behavioral analysis in NPC1 mutant mice upon CYCLO/ALLO/miglustat therapy.
      NPC1 mutant (BALB/cJ NPC1NIH) and control mice were used. For the combination
      treatment mice were injected with CYCLO/ALLO weekly, starting at P7. The
      miglustat injection was performed daily from P10 till P23. Starting at P23,
      miglustat was added to the powdered chow. For the sham treatment of control and
      mutant mice the same schedule was used with 0.9% NaCl injection. Locomotor
      activity was assessed in open field, elevated plus maze and accelerod tests. For
      assessment of spatial learning and memory the Morris water maze test was
      conducted. Electron microscopy has been performed to support the behavioral data.
      The sham-treated mutant mice exhibited motor impairments in all performed tests.
      In the water maze the sham-treated mutants exhibited impairment in remembering
      the location of the hidden platform. CYCLO/ALLO/miglustat treatment positively
      influenced motor dysfunction: total distance and number of visits significantly
      increased, and accelerod performance improved. The spatial learning, however, did
      not benefit from therapy. At the morphological level, an excessive accumulation
      of electron-dense material was seen in the cerebellar Purkinje cells of mutant
      mice. A regression of these autophagosomal inclusions was seen upon therapy.
      CYCLO/ALLO/miglustat therapy ameliorates motor but not cognitive deficits in NPC1
      mutant mice, suggesting unequal vulnerability of different brain areas to the
      treatment.

PMID- 23948641
TI  - AQP1 expression alterations affect morphology and water transport in Schwann
      cells and hypoxia-induced up-regulation of AQP1 occurs in a HIF-1alpha-dependent
      manner.
AB  - Aquaporin-1 (AQP1) is the principle water channel in the peripheral nervous
      system (PNS) and is specifically localized to Schwann cells in the PNS. However,
      the pathophysiological role of AQP1 in peripheral nerves is poorly understood.
      Here, we utilized RNA interference by lentiviral transduction to specifically
      down-regulate AQP1 expression and a lentiviral overexpression protocol to up
      regulate AQP1 expression, in primary Schwann cell cultures. AQP1 gene silencing
      resulted in a cell shrinkage phenotype, while AQP1 gene overexpression caused a
      cell swelling phenotype, as validated by cell volume determinations. Secondly, we
      utilized an in vitro hypoxia model in Schwann cells to mimic in vivo facial nerve
      injury. We demonstrated that AQP1 expression was induced within 8h following
      hypoxia injury in vitro, and that AQP1 knockdown (KD) caused the cells to resist
      edema following hypoxia. Finally, we investigated the hypoxic regulation of the
      AQP1 gene, as well as the involvement of Hypoxia-inducible factor-1alpha (HIF
      1alpha) in AQP1 modulation and we found that KD of HIF-1alpha decreased hypoxia
      dependent induction of endogenous AQP1 expression at both the mRNA and protein
      levels. Taken together, these results indicate that (1) AQP1 is an important
      factor responsible for the fast water transport of cultured Schwann cells and is
      involved in cell plasticity; (2) AQP1 alterations may be a primary factor in
      hypoxia-induced peripheral nerve edema; (3) HIF-1alpha participates in the
      hypoxic induction of the AQP1 gene; (4) AQP1 inhibition might provide a new
      therapeutic alternative for the treatment of some forms of peripheral nerve
      edema.

PMID- 23948642
TI  - Simple integer risk score to determine prognosis of patients with hypertension
      and chronic stable coronary artery disease.
AB  - BACKGROUND: It is difficult to accurately determine prognosis of patients with
      hypertension and chronic stable coronary artery disease (CAD). Our aim was to
      construct a risk score for predicting important adverse events in this
      population. METHODS AND RESULTS: Patients with hypertension and chronic stable
      CAD enrolled in the INternational VErapamil-SR/Trandolapril STudy (INVEST)
      comprised the study cohort. Candidate predictor variables were obtained from
      patients with at least 1 postbaseline visit. Patients were divided into
      development (n=18 484) and validation cohorts (n=2054). Cox regression model
      identified predictors of the primary outcome: all-cause mortality, myocardial
      infarction, or stroke at a mean follow-up of 2.3 years. The hazard ratio of each
      variable was rounded to the nearest integer to construct score weights. A score 0
      to 4 defined low-risk, 5 to 6 intermediate-risk and >=7 high-risk. The following
      variables were retained in the final model: age, residence, body mass index, on
      treatment heart rate and BP, prior myocardial infarction, heart failure,
      stroke/transient ischemic attack, smoking, diabetes, peripheral arterial disease,
      and chronic kidney disease. The primary outcome occurred in 2.9% of the low-risk
      group, 6.5% of the intermediate-risk group, and 18.0% of the high-risk group (P
      for trend <0.0001). The model was good at discriminating those who had an event
      versus those who did not (C-statistic=0.75). The model performed well in a
      validation cohort (C-statistic=0.77). CONCLUSION: Readily available clinical
      variables can rapidly stratify patients with hypertension and chronic stable CAD
      into useful risk categories.

PMID- 23948643
TI  - Circulating levels of miR-133a predict the regression potential of left
      ventricular hypertrophy after valve replacement surgery in patients with aortic
      stenosis.
AB  - BACKGROUND: Myocardial microRNA-133a (miR-133a) is directly related to reverse
      remodeling after pressure overload release in aortic stenosis patients. Herein,
      we assessed the significance of plasma miR-133a as an accessible biomarker with
      prognostic value in predicting the reversibility potential of LV hypertrophy
      after aortic valve replacement (AVR) in these patients. METHODS AND RESULTS: The
      expressions of miR-133a and its targets were measured in LV biopsies from 74
      aortic stenosis patients. Circulating miR-133a was measured in peripheral and
      coronary sinus blood. LV mass reduction was determined echocardiographically.
      Myocardial and plasma levels of miR-133a correlated directly (r=0.46, P<0.001)
      supporting the myocardium as a relevant source of plasma miR-133a. Accordingly, a
      significant gradient of miR-133a was found between coronary and systemic venous
      blood. The preoperative plasma level of miR-133a was higher in the patients who
      normalized LV mass 1 year after AVR than in those exhibiting residual
      hypertrophy. Logistic regression analysis identified plasma miR-133a as a
      positive predictor of the hypertrophy reversibility after surgery. The
      discrimination of the model yielded an area under the receiver operator
      characteristic curve of 0.89 (P<0.001). Multiple linear regression analysis
      revealed plasma miR-133a and its myocardial target Wolf-Hirschhorn syndrome
      candidate 2/Negative elongation factor A as opposite predictors of the LV mass
      loss (g) after AVR. CONCLUSIONS: Preoperative plasma levels of miR-133a reflect
      their myocardial expression and predict the regression potential of LV
      hypertrophy after AVR. The value of this bedside information for the surgical
      timing, particularly in asymptomatic aortic stenosis patients, deserves
      confirmation in further clinical studies.

PMID- 23948644
TI  - Risk of deep vein thrombosis in patients with cellulitis and erysipelas: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: The occurrence of deep vein thrombosis (DVT) is often considered in
      patients with cellulitis and erysipelas because of the common presentation of
      unilateral limb swelling, erythema and pain. Different authors however have
      reached different conclusions about the prevalence of DVT in these patients and
      for the need for compression ultrasound (CUS). The purpose of this study is to
      determine the prevalence of DVT in patients with cellulitis and erysipelas, and
      inform the utility of CUS. METHODS: A systematic literature search was conducted
      of Medline and Cochrane for studies that reported groups of patients with
      cellulitis or erysipelas who had CUS to evaluate for DVT. Study quality
      assessment was based on the Newcastle-Ottawa Quality Assessment Scale for Cohort
      Studies. The incidence rates from the included studies were pooled using a random
      effects model to calculate an overall DVT rate. Individual and pooled DVT rates
      with corresponding upper and lower limits were graphed as a forest plot. Between
      study heterogeneity was estimated using the I(2) statistic. RESULTS: Nine studies
      were included totaling 1054 patients with cellulitis or erysipelas with 18 DVTs.
      The overall pooled incidence rate was 2.1% (95% confidence interval, 0.5%-9.1%)
      for proximal DVT and 3.1% (95% confidence interval, 1.9%-4.9%) for any DVT. When
      analyzed separately, the pooled incidence rate for the three retrospective
      studies was 1.1% (95% CI, 0.6%-2.2%), while the rate for the six prospective
      studies was 7.8% (95% CI, 4.2%-14.2%). CONCLUSION: The risk of DVT in cellulitis
      and erysipelas is low compared to the average risk of patients referred for CUS
      and comparable to low risk patients as determined by the commonly employed Wells
      criteria.

PMID- 23948646
TI  - Consumer health information technology in an adult public health primary care
      clinic: a heart health education feasibility study.
AB  - OBJECTIVE: To explore the feasibility and short term outcomes of using an
      interactive kiosk integrated into office flow to deliver health information in a
      primary care clinic. METHODS: Fifty-one adults with BMI >=25 were randomly
      assigned to use a kiosk with attached devices to receive a six-week healthy
      eating/weight monitoring (intervention) or general health/BP monitoring
      (attention-control) program. Outcomes were measured at baseline, 8 weeks (post)
      and three month follow-up. RESULTS: Participants completed an average of 2.73
      weekly sessions, with transportation and time given as limiting factors. They
      found the kiosk easy to use (97%), liked the touchscreen (94%), and would use the
      kiosk again (81%). Although there were no differences between groups, the 27
      completing all assessments showed reduced weight (p=.02), and decreased systolic
      (p=.01) and diastolic BP (p<.001) at follow-up. Although healthy eating behaviors
      increased, the change was not statistically significant. CONCLUSION: Using a
      kiosk within a clinic setting is a feasible method of providing health
      information and self-monitoring. Multi-session educational content can provide
      beneficial short-term outcomes in overweight adults. PRACTICE IMPLICATIONS: A
      kiosk with attached peripherals in a clinic setting is a viable adjunct to
      provider education, particularly in medically underserved areas.

PMID- 23948645
TI  - The functional architecture for face-processing expertise: FMRI evidence of the
      developmental trajectory of the core and the extended face systems.
AB  - Expertise in processing faces is a cornerstone of human social interaction.
      However, the developmental course of many key brain regions supporting face
      preferential processing in the human brain remains undefined. Here, we present
      findings from an FMRI study using a simple viewing paradigm of faces and objects
      in a continuous age sample covering the age range from 6 years through adulthood.
      These findings are the first to use such a sample paired with whole-brain FMRI
      analyses to investigate development within the core and extended face networks
      across the developmental spectrum from middle childhood to adulthood. We found
      evidence, albeit modest, for a developmental trend in the volume of the right
      fusiform face area (rFFA) but no developmental change in the intensity of
      activation. From a spatial perspective, the middle portion of the right fusiform
      gyrus most commonly found in adult studies of face processing was increasingly
      likely to be included in the FFA as age increased to adulthood. Outside of the
      FFA, the most striking finding was that children hyperactivated nearly every
      aspect of the extended face system relative to adults, including the amygdala,
      anterior temporal pole, insula, inferior frontal gyrus, anterior cingulate gyrus,
      and parietal cortex. Overall, the findings suggest that development is best
      characterized by increasing modulation of face-sensitive regions throughout the
      brain to engage only those systems necessary for task requirements. 

PMID- 23948647
TI  - An mRNA atlas of G protein-coupled receptor expression during primary human
      monocyte/macrophage differentiation and lipopolysaccharide-mediated activation
      identifies targetable candidate regulators of inflammation.
AB  - G protein-coupled receptors (GPCRs) are among the most important targets in drug
      discovery. In this study, we used TaqMan Low Density Arrays to profile the full
      GPCR repertoire of primary human macrophages differentiated from monocytes using
      either colony stimulating factor-1 (CSF-1/M-CSF) (CSF-1 Mphi) or granulocyte
      macrophage colony stimulating factor (GM-CSF) (GM-CSF Mphi). The overall trend
      was a downregulation of GPCRs during monocyte to macrophage differentiation, but
      a core set of 10 genes (e.g. LGR4, MRGPRF and GPR143) encoding seven
      transmembrane proteins were upregulated, irrespective of the differentiating
      agent used. Several of these upregulated GPCRs have not previously been studied
      in the context of macrophage biology and/or inflammation. As expected, CSF-1 Mphi
      and GM-CSF Mphi exhibited differential inflammatory cytokine profiles in response
      to the Toll-like Receptor (TLR)4 agonist lipopolysaccharide (LPS). Moreover, 15
      GPCRs were differentially expressed between these cell populations in the basal
      state. For example, EDG1 was expressed at elevated levels in CSF-1 Mphi versus GM
      CSF Mphi, whereas the reverse was true for EDG6. 101 GPCRs showed differential
      regulation over an LPS time course, with 65 of these profiles being impacted by
      the basal differentiation state (e.g. GPRC5A, GPRC5B). Only 14 LPS-regulated
      GPCRs showed asynchronous behavior (divergent LPS regulation) with respect to
      differentiation status. Thus, the differentiation state primarily affects the
      magnitude of LPS-regulated expression, rather than causing major reprogramming of
      GPCR gene expression profiles. Several GPCRs showing differential profiles
      between CSF-1 Mphi and GM-CSF Mphi (e.g. P2RY8, GPR92, EMR3) have not been widely
      investigated in macrophage biology and inflammation. Strikingly, several closely
      related GPCRs displayed completely opposing patterns of regulation during
      differentiation and/or activation (e.g. EDG1 versus EDG6, LGR4 versus LGR7,
      GPRC5A versus GPRC5B). We propose that selective regulation of GPCR5A and GPCR5B
      in CSF-1 Mphi contributes to skewing toward the M2 macrophage phenotype. Our
      analysis of the GPCR repertoire expressed during primary human monocyte to
      macrophage differentiation and TLR4-mediated activation provides a valuable new
      platform for conducting future functional analyses of individual GPCRs in human
      macrophage inflammatory pathways. 

PMID- 23948648
TI  - In reply.

PMID- 23948649
TI  - Use of grading scales in venous air emboli during neurosurgery.

PMID- 23948650
TI  - Adult-derived pluripotent stem cells.
AB  - The global incidence of spinal cord injury (SCI) is 15-40 cases per million
      people, with the socioeconomic and healthcare costs amounting to nearly $10
      billion per annum in the USA alone. Despite substantial advances in medical care
      and surgical technology, many patients with SCI still experience significant long
      term neurologic disability. Cellular transplantation offers a promising therapy
      to address the multifactorial nature of SCI in both the subacute and chronic
      phase of the injury to promote central nervous system repair and regeneration and
      to augment existing therapies. Adult-derived stem cells are the least ethically
      challenging stem cells but, until recently, a major hurdle has been inducing
      pluripotency to generate the required neural lineages. Improved generation and
      transfection techniques, combined with positive experimental outcomes in SCI
      models, suggest that adult-derived induced pluripotent stem cells could be a
      genuine alternative to embryonic stem cells for clinical treatments. For
      translation from bench to bedside, the efficacy of induced pluripotent stem cell
      derived neural stem and progenitor cells in suitable SCI models needs to be
      validated further and backed up with rigorous early-stage clinical trials. 

PMID- 23948652
TI  - Artificial ferroic systems: novel functionality from structure, interactions and
      dynamics.
AB  - Lithographic processing and film growth technologies are continuing to advance,
      so that it is now possible to create patterned ferroic materials consisting of
      arrays of sub-1 MUm elements with high definition. Some of the most fascinating
      behaviour of these arrays can be realised by exploiting interactions between the
      individual elements to create new functionality. The properties of these
      artificial ferroic systems differ strikingly from those of their constituent
      components, with novel emergent behaviour arising from the collective dynamics of
      the interacting elements, which are arranged in specific designs and can be
      activated by applying magnetic or electric fields. We first focus on artificial
      spin systems consisting of arrays of dipolar-coupled nanomagnets and, in
      particular, review the field of artificial spin ice, which demonstrates a wide
      range of fascinating phenomena arising from the frustration inherent in
      particular arrangements of nanomagnets, including emergent magnetic monopoles,
      domains of ordered macrospins, and novel avalanche behaviour. We outline how
      demagnetisation protocols have been employed as an effective thermal anneal in an
      attempt to reach the ground state, comment on phenomena that arise in thermally
      activated systems and discuss strategies for selectively generating specific
      configurations using applied magnetic fields. We then move on from slow field and
      temperature driven dynamics to high frequency phenomena, discussing spinwave
      excitations in the context of magnonic crystals constructed from arrays of
      patterned magnetic elements. At high frequencies, these arrays are studied in
      terms of potential applications including magnetic logic, linear and non-linear
      microwave optics, and fast, efficient switching, and we consider the possibility
      to create tunable magnonic crystals with artificial spin ice. Finally, we discuss
      how functional ferroic composites can be incorporated to realise magnetoelectric
      effects. Specifically, we discuss artificial multiferroics (or multiferroic
      composites), which hold promise for new applications that involve electric field
      control of magnetism, or electric and magnetic field responsive devices for high
      frequency integrated circuit design in microwave and terahertz signal processing.
      We close with comments on how enhanced functionality can be realised through
      engineering of nanostructures with interacting ferroic components, creating
      opportunities for novel spin electronic devices that, for example, make use of
      the transport of magnetic charges, thermally activated elements, and
      reprogrammable nanomagnet systems.

PMID- 23948651
TI  - Hand-Schuller-Christian disease associated with symptomatic cavum septi pellucidi
      cyst in an adult with a 10-year follow-up.

PMID- 23948653
TI  - The impact factor of circulation research rises 25%.

PMID- 23948655
TI  - Preface for the special issue celebrating Stephen Weiner's 65th birthday.

PMID- 23948654
TI  - Altered expression of Raet1e, a major histocompatibility complex class 1-like
      molecule, underlies the atherosclerosis modifier locus Ath11 10b.
AB  - RATIONALE: Quantitative trait locus mapping of an intercross between C57.Apoe-/-
      and FVB.Apoe-/- mice revealed an atherosclerosis locus controlling aortic root
      lesion area on proximal chromosome 10, Ath11. In a previous work, subcongenic
      analysis showed Ath11 to be complex with proximal (10a) and distal (10b) regions.
      OBJECTIVE: To identify the causative genetic variation underlying the
      atherosclerosis modifier locus Ath11 10b. METHODS AND RESULTS: We now report
      subcongenic J, which narrows the 10b region to 5 genes, Myb, Hbs1L, Aldh8a1,
      Sgk1, and Raet1e. Sequence analysis of these genes revealed no amino acid coding
      differences between the parental strains. However, comparing aortic expression of
      these genes between F1.Apoe-/- Chr10SubJ((B/F)) and F1.Apoe-/- Chr10SubJ((F/F))
      uncovered a consistent difference only for Raet1e, with decreased, virtually
      background, expression associated with increased atherosclerosis in the latter.
      The key role of Raet1e was confirmed by showing that transgene-induced aortic
      overexpression of Raet1e in F1.Apoe-/- Chr10SubJ((F/F)) mice decreased
      atherosclerosis. Promoter reporter constructs comparing C57 and FVB sequences
      identified an FVB mutation in the core of the major aortic transcription start
      site abrogating activity. CONCLUSIONS: This nonbiased approach has revealed
      Raet1e, a major histocompatibility complex class 1-like molecule expressed in
      lesional aortic endothelial cells and macrophage-rich regions, as a novel
      atherosclerosis gene and represents one of the few successes of the quantitative
      trait locus strategy in complex diseases.

PMID- 23948656
TI  - Knowledge and beliefs about epilepsy among people with and without epilepsy in
      urban Suriname.
AB  - Reducing the burden of epilepsy in low- and middle-income countries requires
      understanding of the cultural aspects of epilepsy. This cross-sectional study
      among individuals attending a clinic in an urban setting in Paramaribo, Suriname
      aimed to obtain information on the knowledge of and attitudes towards epilepsy
      and epilepsy treatment, comparing people with epilepsy (PWE) to those without
      epilepsy. This study also explored the help-seeking behavior and experience of
      having epilepsy in PWE. While the results of interviews with 49 PWE and 33
      controls compared favorably to studies conducted in similar countries, a
      significant minority of PWE still rely on traditional remedies. Prejudices
      regarding social roles, schooling, and occupational choices of PWE also remain
      prevalent. Currently, the major source of information for both groups is the
      media, but there could be opportunities for the local epilepsy association to
      play a larger role. These findings, despite some selection bias, could be useful
      in bringing conventional medical treatment strategies to more PWE in Suriname, as
      well as empower patient organizations in designing stigma-reducing interventions.

PMID- 23948657
TI  - Managing Epilepsy Well: Emerging e-Tools for epilepsy self-management.
AB  - The Managing Epilepsy Well (MEW) Network was established in 2007 by the Centers
      for Disease Control and Prevention Epilepsy Program to expand epilepsy self
      management research. The network has employed collaborative research strategies
      to develop, test, and disseminate evidence-based, community-based, and e-Health
      interventions (e-Tools) for epilepsy self-management for people with epilepsy,
      caregivers, and health-care providers. Since its inception, MEW Network
      collaborators have conducted formative studies (n=7) investigating the potential
      of e-Health to support epilepsy self-management and intervention studies
      evaluating e-Tools (n=5). The MEW e-Tools (the MEW website, WebEase, UPLIFT,
      MINDSET, and PEARLS online training) and affiliated e-Tools (Texting 4 Control)
      are designed to complement self-management practices in each phase of the
      epilepsy care continuum. These tools exemplify a concerted research agenda,
      shared methodological principles and models for epilepsy self-management, and a
      communal knowledge base for implementing e-Health to improve quality of life for
      people with epilepsy. 

PMID- 23948658
TI  - An independent validation association study of carcass quality, shear force,
      intramuscular fat percentage and omega-3 polyunsaturated fatty acid content with
      gene markers in Australian lamb.
AB  - Previous association studies revealed several single nucleotide polymorphisms
      (SNPs) that explained the observed phenotypic variation for meat tenderness and
      long-chain omega-3 polyunsaturated fatty acid (PUFA) content of Australian lamb.
      To confirm the validity of these associated SNPs at predicting meat tenderness
      and omega-3 PUFA content, an independent validation study was designed. The
      OvineSNP50 genotypes of these animals were used to impute the 192 SNP Meat
      Quality Research (MQR) panel genotypes on nearly 6200 animals from the
      Cooperative Research Centre for Sheep Industry Innovation Information Nucleus
      Flock and Sheep Genomics Falkiner Memorial Field Station flock. Association
      analysis revealed numerous SNP from the 192 SNP MQR panel that were associated
      with carcass quality - fat depth at the C-site and eye muscle depth; shear force
      at day 1 and day 5 after slaughter (SF1 and SF5); and omega-3 PUFA content at
      P<0.01. However, 1 SNP was independently validated for SF5 (i.e. CAST_101781475).
      The magnitude of the effect of each significant SNP and the relative allele
      frequencies across Merino-, Maternal- and Terminal-sired progeny was determined.
      The independently validated SNP for SF5 and the associated SNP with omega-3 PUFA
      content will accelerate efforts to improve these phenotypic traits in Australian
      lamb. 

PMID- 23948659
TI  - Molecular dynamics simulation of dipalmitoylphosphatidylcholine modified with a
      MTSL nitroxide spin label in a lipid membrane.
AB  - We investigate the interaction between dipalmitoylphosphatidylcholine (DPPC) and
      a nitroxide spin label in order to understand its influences on lipid structure
      and dynamics using molecular dynamics simulations. The system was modified by
      covalently attaching nitroxide spin labels to the headgroups of two DPPC
      molecules. (S-(2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl
      methanesulfonothioate) (MTSL) was used as the spin label. The label position and
      dynamics were analyzed as was the impact of the modified DPPC on the structure of
      the surrounding lipids. The modified DPPC molecules locate closer to the center
      of the membrane than unmodified DPPC molecules. The rotation of the spin label is
      unrestricted, but there are favored orientations. MTSL depresses the deuterium
      order parameters of the carbon atoms close to the headgroup in surrounding DPPC
      molecules. The spin label has no impact on order parameters of carbon atoms at
      the end of the lipid tails. The lateral diffusion constant of the modified DPPC
      is indistinguishable from unmodified DPPC molecules. These novel computational
      results suggest an experimental validation. 

PMID- 23948660
TI  - Validation of the Body Dysmorphic Disorder Questionnaire in a community sample of
      Swedish women.
AB  - Body Dysmorphic Disorder (BDD) is characterized by a distressing and impairing
      preoccupation with a nonexistent or slight defect in appearance. Patients with
      the disorder present to both psychiatric and non-psychiatric physicians. A few
      studies have assessed BDD prevalence in the general population and have shown
      that the disorder is relatively common. To date, no BDD assessment instruments
      have been validated in the general population. Our aim was to validate a brief
      self-screening instrument, the Body Dysmorphic Disorder Questionnaire (BDDQ), in
      a female community sample. The BDDQ was translated into Swedish and filled out by
      2891 women from a randomly selected community sample. The questionnaire was
      validated in a subsample of 88 women, using the Structured Clinical Interview for
      DSM-IV (SCID) together with clinical assessment as the gold standard. In the
      validation subsample, the BDDQ showed good concurrent validity, with a
      sensitivity of 94%, a specificity of 90% and a likelihood ratio of 9.4. The
      questionnaire can therefore be of value when screening for BDD in female
      populations. 

PMID- 23948661
TI  - Course of irritability, depression and apathy in Huntington's disease in relation
      to motor symptoms during a two-year follow-up period.
AB  - BACKGROUND: Irritability, depression and apathy are frequently reported
      neuropsychiatric symptoms of Huntington's disease (HD). OBJECTIVE: This study
      investigated the course of irritability, depression and apathy in HD during a 2
      year follow-up period. METHODS: In 121 HD mutation carriers the presence of
      irritability, depression and apathy was measured with the Problem Behaviours
      Assessment (PBA). Multivariate linear regression analysis was performed to assess
      their relationships with the change of the motor score of the Unified
      Huntington's Disease Rating Scale (UHDRS-m) in premotor symptomatic (n = 46) and
      motor symptomatic mutation carriers (n = 75). RESULTS: The median depression
      score of all participants decreased (p = 0.002), whereas irritability and apathy
      scores did not change significantly. In the total group of mutation carriers, a
      borderline significant association was found between an increase in motor
      symptoms and an increase in irritability (p = 0.05), and a trend was found for
      the association between an increase in motor symptoms and a decrease in
      depression (p = 0.06). Only in the at baseline premotor symptomatic mutation
      carriers was an increase in motor symptoms significantly related to an increase
      in irritability (p = 0.02). CONCLUSION: An increase in motor symptoms in the at
      baseline premotor symptomatic mutation carriers is related to an increase in
      irritability, which may be an early and sensitive marker for disease progression.

PMID- 23948662
TI  - Evaluating patients' preferences for type of bowel preparation prior to screening
      CT colonography: convenience and comfort versus sensitivity and specificity.
AB  - AIMS: To explore the relative value patients place on comfort and convenience
      versus test sensitivity and specificity in the context of computed tomographic
      colonography (CTC) screening. MATERIALS AND METHODS: Twenty semi-structured
      interviews were carried out with patients attending hospital for radiological
      tests unrelated to CTC. Preferences for CTC with different types of bowel
      preparation for CTC screening were examined and interviews were analysed
      thematically. The discussion guide included separate sections on CTC, bowel
      preparation methods (non-, reduced- and full-laxative), and sensitivity and
      specificity. Patients were given information on each topic in turn and asked
      about their views and preferences during each section. RESULTS: Following
      information about the test, patients' attitudes towards CTC were positive.
      Following information on bowel preparation, full-laxative purgation was
      anticipated to cause more adverse physical and lifestyle effects than using
      reduced- or non-laxative preparation. However, stated preferences were
      approximately equally divided, largely due to patients anticipating that non
      laxative preparations would reduce test accuracy (because the bowel was not
      thoroughly cleansed). Following information on sensitivity and specificity (which
      supported patients' expectations), the predominant stated preference was for full
      laxative preparation. CONCLUSIONS: Patients are likely to value test sensitivity
      and specificity over a more comfortable and convenient preparation. Future
      research should test this hypothesis on a larger sample.

PMID- 23948663
TI  - The Bristol Radiology Report Assessment Tool (BRRAT): developing a workplace
      based assessment tool for radiology reporting skills.
AB  - AIM: To review the development of a workplace-based assessment tool to assess the
      quality of written radiology reports and assess its reliability, feasibility, and
      validity. MATERIALS AND METHODS: A comprehensive literature review and rigorous
      Delphi study enabled the development of the Bristol Radiology Report Assessment
      Tool (BRRAT), which consists of 19 questions and a global assessment score. Three
      assessors applied the assessment tool to 240 radiology reports provided by 24
      radiology trainees. RESULTS: The reliability coefficient for the 19 questions was
      0.79 and the equivalent coefficient for the global assessment scores was 0.67.
      Generalizability coefficients demonstrate that higher numbers of assessors and
      assessments are needed to reach acceptable levels of reliability for summative
      assessments due to assessor subjectivity. CONCLUSION: The study methodology gives
      good validity and strong foundation in best-practice. The assessment tool
      developed for radiology reporting is reliable and most suited to formative
      assessments.

PMID- 23948664
TI  - Opposite behavior of plasma levels surfactant protein type B and receptor for
      advanced glycation end products in pulmonary sarcoidosis.
AB  - BACKGROUND: No biological marker is currently available for evaluating pulmonary
      involvement and/or for monitoring the clinical course of sarcoidosis. The present
      pilot study focused on possible relationships between circulating plasma levels
      of surfactant protein type B (SP-B) and plasma receptor for advanced glycation
      end products (RAGE) and lung function abnormalities in patients with pulmonary
      sarcoidosis, since both SP-B and RAGE have been previously suggested as lung
      injury markers. The plasmatic levels of these two proteins were also investigated
      with respect to functional capacity, as assessed by a cardiopulmonary exercise
      test (CPET). METHODS: Thirty pulmonary sarcoidosis outpatients and fifteen
      volunteers (Control Group) underwent lung function tests and CPET. Resting SP-B
      and RAGE plasma levels were also determined. Patients were then categorized
      according to the severity of their pulmonary involvement, as assessed in terms of
      lung diffusion for carbon monoxide (DLCO) values. RESULTS: Group B showed SP-B
      levels higher and RAGE levels lower than Group A and Control Group (p < 0.01).
      Group A showed lower RAGE levels than Control Group (p < 0.01), whereas SP-B
      levels did not differ between these two groups. A significant univariate
      relationship was found between both SP-B and RAGE and several lung function data,
      particularly with DLCO (SP-B Vs DLCO: r: -0.437, p = 0.016; RAGE Vs DLCO: r: 
      0.451, p = 0.012). CONCLUSIONS: Circulating plasma levels of SP-B and RAGE showed
      an opposite behavior in patients with pulmonary sarcoidosis. SP-B values are
      directly related to alveolar unit damage, supporting a possible role of SP-B as a
      marker of disease severity in these patients. Differently, RAGE decreases in
      severe sarcoidosis, suggesting more complex underlying mechanisms.

PMID- 23948666
TI  - Relationship between the preferred chewing side and the angulation of anterior
      tooth guidance.
AB  - OBJECTIVES: The aim of this study was to evaluate a possible relationship between
      preferred chewing side (PCS) and the anterior guidance angle. SUBJECTS AND
      METHODS: Forty dental nurses and technicians, aged 24-46 years, were each given a
      piece of chewing gum, which they chewed for about 3 min. At 7 regular intervals
      (every 15 s), they were interrupted by the principal investigator (P.L.) in order
      to observe on which side of their mouths they had the bolus of chewing gum.
      Moulds of their jaws were made and the position of the maxillary arch relative to
      temporomandibular joints was recorded with a facebow and transferred to a semi
      adjustable articulator. After mounting the stone casts of each subject, a measure
      of the anterior guidance angle was taken with an adjustable incisal table.
      RESULTS: Of the 40 subjects, 14 (35%) presented a PCS. Among the 14 subjects who
      preferred a chewing side, there was a correlation between the PCS and a low
      angulation of teeth constituting the anterior guidance on that side, but this
      correlation was statistically nonsignificant. CONCLUSION: In this study, we found
      that unilateral chewing creates uneven wear on the anterior teeth and changed the
      anterior guidance angulation.

PMID- 23948665
TI  - Functional expression of choline transporter-like protein 1 (CTL1) in small cell
      lung carcinoma cells: a target molecule for lung cancer therapy.
AB  - Choline is essential for the synthesis of the major membrane phospholipid
      phosphatidylcholine and the neurotransmitter acetylcholine (ACh). Elevated levels
      of choline and up-regulated choline kinase activity have been detected in cancer
      cells. Thus, the intracellular accumulation of choline through choline
      transporters is the rate-limiting step in phospholipid metabolism and a
      prerequisite for cancer cell proliferation. However, the uptake system for
      choline and the functional expression of choline transporters in lung cancer
      cells are poorly understood. We examined the molecular and functional
      characterization of choline uptake in the small cell lung carcinoma cell line NCI
      H69. Choline uptake was saturable and mediated by a single transport system.
      Interestingly, removal of Na(+) from the uptake buffer strongly enhanced choline
      uptake. This increase in choline uptake under the Na(+)-free conditions was
      inhibited by dimethylamiloride (DMA), a Na(+)/H(+) exchanger (NHE) inhibitor.
      Various organic cations and the choline analog hemicholinium-3 (HC-3) inhibited
      the choline uptake and cell viability. A correlation analysis of the potencies of
      organic cations for the inhibition of choline uptake and cell viability showed a
      strong correlation (R=0.8077). RT-PCR revealed that choline transporter-like
      protein 1 (CTL1) mRNA and NHE1 are mainly expressed. HC-3 and CTL1 siRNA
      inhibited choline uptake and cell viability, and increased caspase-3/7 activity.
      The conversion of choline to ACh was confirmed, and this conversion was enhanced
      under Na(+)-free conditions, which in turn was sensitive to HC-3. These results
      indicate that choline uptake through CTL1 is used for ACh synthesis. Both an
      acetylcholinesterase inhibitor (eserine) and a butyrylcholinesterase inhibitor
      (ethopropazine) increased cell proliferation, and these effects were inhibited by
      4-DAMP, a mAChR3 antagonist. We conclude that NCI-H69 cells express the choline
      transporter CTL1 which uses a directed H(+) gradient as a driving force, and its
      transport functions in co-operation with NHE1. This system primarily supplies
      choline for the synthesis of ACh and secretes ACh to act as an
      autocrine/paracrine growth factor, and the functional inhibition of CTL1 could
      promote apoptotic cell death. Identification of this new CTL1-mediated choline
      transport system provides a potential new target for therapeutic intervention. 

PMID- 23948667
TI  - Histopathological alterations in the brain (optic tectum) of the fresh water
      teleost Channa punctatus in response to acute and subchronic exposure to the
      pesticide Chlorpyrifos.
AB  - In the present investigation an attempt was made to assess the toxicity of the
      organophosphate pesticide Chlorpyrifos (0,0-diethyl-0-3,5,6-trichloro-2-pyridyl
      phosphorothioate; CPF) on the brain (optic tectum) of the teleost Channa
      punctatus (Bloch). Fish were exposed to acute (1.5, 3.0, 4.5, 6.0 and 7.5 MUl/l)
      for 24 h and sublethal concentrations of CPF 1.79 MUl/l (1/3 of LC50) and 0.538
      MUl/l (1/10 of LC50) for 3 and 7 days respectively. Several endpoints related to
      the histoarchitectural profile in the optic tectum were evaluated. Histological
      examination showed detachment in the superficial zone of the Stratum opticum,
      Str. marginale due to degeneration of neuronal cells. Spongiosis, congestion,
      necrosis and appearance of clear areas around the nucleus of mononuclear cells in
      the lining of the Str. fibrosum grisium superficiale, Str. griseum centrale, Str.
      album centrale were seen. Granular cells found in the innermost layer of optic
      tectum, i.e. the Str. periventriculare, were severely degenerated and vacuolized
      and they migrated toward the Torus semicircularis. The histopathological changes
      were more pronounced with higher concentrations of CPF. The degree of
      neurodegeneration found in the deep layers of the optic tectum in higher
      concentration treatment (6.0 and 7.5 MUl/l) was more pronounced. These
      alterations of the optic tectum affected the functioning of motor coordination of
      the fish body, because CPF inhibited acetylcholine in neuronal synapses. Due to
      apoptosis in the superficial zone of the optic tectum, normal visual response was
      affected. Fish showed microphthalmia (reduced size and eye shrinkage in the eye
      orbit) because of detachment, necrosis, degeneration and vacuolization in
      different regions after CPF treatment. This study shows that CPF is highly toxic
      to fish and affect their population survival in environment.

PMID- 23948668
TI  - Keratinization of the esophageal epithelium of domesticated mammals.
AB  - We studied the esophageal epithelium for keratinization characteristics from
      samples of domesticated mammals of three nutrition groups (herbivores: horse,
      cattle, sheep; omnivores: pig, dog, rat; carnivores: cat) using histochemistry
      (keratins, disulfides), sulfur measurements, and cryo-SEM. Keratins were found in
      all esophageal layers of all species, except for the equine Stratum corneum. The
      positive reaction staining of Pan-keratin was remarkable, but decreased in
      intensity toward the outer layers, whereas in the pig and cat, staining was
      confined to the corneal layer. The herbivores revealed positive staining
      reactions in the upper Stratum spinosum, particularly in the sheep. Regarding
      single keratins, CK6 immunostating was found in most esophageal layers, but only
      weakly or negatively in the porcine and equine Stratum corneum. CK13 staining was
      restricted to the sheep and here was found in all layers. CK14 could be detected
      in the equine and feline Stratum basale, and upper vital layers of the dog and
      rat. CK17 appeared only in the Stratum spinosum and Stratum granulosum, but in
      all layers of the dog and cat. Disulfides reacted strongest in the Stratum
      corneum of the herbivores, as corroborated by the sulfur concentrations in the
      esophagus. Our study emphasized that keratins are very important for the
      mechanical stability of the epithelial cells and cell layers of the mammalian
      esophagus. The role of these keratins in the esophageal epithelia is of specific
      interest owing to the varying feed qualities and mechanical loads of different
      nutrition groups, which have to be countered. 

PMID- 23948669
TI  - Feasibility and safety of endovascular treatment for chronic cerebrospinal venous
      insufficiency in patients with multiple sclerosis.
AB  - OBJECTIVE: Chronic cerebrospinal venous insufficiency (CCSVI) is a recently
      discovered syndrome mainly due to stenoses of internal jugular (IJV) and/or
      azygos (AZ) veins. The present study retrospectively evaluates the feasibility
      and safety of endovascular treatment for CCSVI in a cohort of patients with
      multiple sclerosis (MS). METHODS: From September 2010 to October 2012, 1202
      consecutive patients were admitted to undergo phlebograpy +/- endovascular
      treatment for CCSVI. All the patients had previously been found positive at color
      Doppler sonography (CDS) for at least two Zamboni criteria for CCSVI and had a
      neurologist-confirmed diagnosis of MS. Only symptomatic MS were considered for
      treatment. Percutaneous transluminal angioplasty was carried out as an outpatient
      procedure at two different institutes. Primary procedures, regarded as the first
      balloon angioplasty ever performed for CCSVI, and secondary (reintervention)
      procedures, regarded as interventions performed after venous disease recurrence,
      were carried out in 86.5% (1037 of 1199) and 13.5% (162 of 1199) of patients,
      respectively. Procedural success and complications within 30 days were recorded.
      RESULTS: Phlebography followed by endovascular recanalization was carried out in
      1999 patients consisting of 1219 interventions. Balloon angioplasty alone was
      performed in 1205 out of 1219 (98.9%) procedures, whereas additional stent
      placement was required in the remaining 14 procedures (1.1%) following
      unsuccessful attempts at AZ dilatation. No stents were ever implanted in the IJV.
      The feasibility rate was as high as 99.2% (1209 interventions). Major
      complications included one (0.1%) AZ rupture occurring during balloon dilatation
      and requiring blood transfusion, one (0.1%) severe bleeding in the groin
      requiring open surgery, two (0.2%) surgical openings of the common femoral vein
      to remove balloon fragments, and three (0.2%) left IJV thromboses. The overall
      major and minor complication rates at 30 days were 0.6% and 2.5%, respectively.
      CONCLUSIONS: Endovascular treatment for CCSVI appears feasible and safe. However,
      a proper learning curve can dramatically lower the rate of adverse events. In our
      experience, the vast majority of complications occurred in the first 400 cases
      performed.

PMID- 23948670
TI  - Role of Girdin in intimal hyperplasia in vein grafts and efficacy of
      atelocollagen-mediated application of small interfering RNA for vein graft
      failure.
AB  - OBJECTIVE: Intimal hyperplasia is a major obstacle to patency in grafted veins.
      Although migration and proliferation of vascular smooth muscle cells (SMCs)
      pivotally affect the vascular remodeling process, no therapy has been established
      to prevent intimal hyperplasia of vein grafts. We previously reported that the
      actin-binding protein Girdin crucially affects arterial remodeling. In this
      study, we investigated the role of Girdin in venous SMCs and evaluated a
      therapeutic strategy for vein graft failure in vivo using small interfering RNA
      (siRNA) that targets Girdin. METHODS: We investigated the relationship between
      Girdin expression and intimal hyperplasia using a rabbit vein graft model. Vein
      grafts under low-flow conditions were performed in Japanese White rabbits. For in
      vitro analyses, we isolated primary venous SMCs from vein graft neointima. siRNA
      that targets Girdin was mixed with atelocollagen, which stabilizes and releases
      nucleic acid reagents slowly and is applied perivascularly to the vein grafts at
      operation. Intimal hyperplasia was evaluated 4 weeks later. RESULTS: In the
      rabbit model, increased Girdin expression was seen in the neointima after the
      grafting operation. Using primary venous SMCs, we showed that Girdin is required
      for rearrangement of the actin cytoskeleton in venous SMCs and that siRNA
      mediated Girdin knockdown significantly reduced venous SMC migration and
      proliferation. Girdin knockdown via perivascular application of siRNA using
      atelocollagen markedly reduced intimal thickening after the grafting operation.
      CONCLUSIONS: Depletion of Girdin attenuated venous SMCs migration and
      proliferation in vitro and intimal hyperplasia in vein grafts in vivo. Our
      findings suggest that Girdin affects migration and proliferation of vascular SMCs
      in vein grafts and that controlled release of Girdin siRNA using atelocollagen
      could be a novel therapeutic strategy for vein graft failure.

PMID- 23948671
TI  - Influence of housing variables on the development of stress-sensitive behaviors
      in the rat.
AB  - Diverse environments early in mammalian life can have profound influences on the
      physiology and behavior of developing offspring. Environmental factors can
      influence offspring development directly or through perturbations in parental
      care. In the current study, we wished to determine if the influence of a single
      environmental variable, type of bedding material used in laboratory cages, is
      capable of altering physiological and behavioral outcomes in offspring. Female
      rats were housed in cages containing wood pulp or corncob bedding and allowed to
      mature. These rats, while housed on assigned bedding material, were bred and
      allowed to give birth. At weaning, male offspring were housed on one of the two
      bedding conditions and tested later in adulthood on stress-sensitive behavioral
      measures. Postmortem analysis of glucocorticoid receptor expression and CRH mRNA
      levels were also measured. Maternal care directed at the pups reared in the two
      different bedding conditions was also recorded. Rats reared from birth on corncob
      bedding exhibited decreased anxiety-like behavior, as adults, in both open field
      and light-dark box tasks compared to wood pulp reared animals. Animals that
      received similar overall levels of maternal care, regardless of bedding
      condition, also differed in anxiety-like behaviors as adults, indicating that the
      bedding condition is capable of altering phenotype independent of maternal care.
      Despite observed behavioral differences in adult offspring reared in different
      bedding conditions, no changes in glucocorticoid receptor expression at the level
      of the hippocampus, frontal cortex, or corticotrophin releasing hormone (CRH)
      mRNA expression in the hypothalamus were observed between groups. These results
      highlight the importance of early life housing variables in programming stress
      sensitive behaviors in adult offspring. 

PMID- 23948672
TI  - Role of thirst and visual barriers in the differential behavior displayed by
      streptozotocin-treated rats in the elevated plus-maze and the open field test.
AB  - Conflicting results have been obtained by several groups when studying the
      effects of streptozotocin (STZ)-treated rats in the elevated plus-maze (EPM).
      Since thirst is a prominent feature in STZ-induced diabetic-like condition, we
      studied whether the walls of the closed arms of the EPM, by limiting the search
      for water in the environment, may contribute to the observed differential
      behavioral outcomes. The aim of this study was to ascertain whether visual
      barriers within the EPM have an influence on the behavior of STZ-treated rats in
      this test of anxiety. A striking similarity between STZ-treated (50 mg/kg, i.p.,
      in two consecutive days) and water deprived rats (72 h) was found in exploratory
      behavior in the EPM, showing an anxiolytic-like profile. However the anxiolytic
      response of STZ-treated rats exposed to the EPM shifts into an anxiogenic profile
      when they are subsequently tested in the open-field test, which unlike the EPM is
      devoid of visual barriers. Likewise, water deprived rats (72 h) also showed an
      anxiogenic profile when they were exposed to the open-field test. Our results
      indicate that experimental outcomes based on EPM observations can be misleading
      when studying physiological or pathological conditions, e.g. diabetes, in which
      thirst may increase exploratory behavior.

PMID- 23948674
TI  - Avocado roots treated with salicylic acid produce phenol-2,4-bis (1,1
      dimethylethyl), a compound with antifungal activity.
AB  - We demonstrated the ability of salicylic acid (SA) to induce a compound in
      avocado roots that strengthens their defense against Phytophthora cinnamomi. The
      SA content of avocado roots, before and after the application of exogenous SA,
      was determined by High-Performance Liquid Chromatography (HPLC). After 4h of SA
      feeding, the endogenous level in the roots increased to 223 MUg g(-1) FW, which
      was 15 times the amount found in control roots. The methanolic extract obtained
      from SA-treated avocado roots inhibited the radial growth of P. cinnamomi. A thin
      layer chromatographic bioassay with the methanolic extract and spores of
      Aspergillus showed a distinct inhibition zone. The compound responsible for the
      inhibition was identified as phenol-2,4-bis (1,1-dimethylethyl) by gas
      chromatography and mass spectrometry. At a concentration of 100 MUg/mL, the
      substance reduced germinative tube length in Aspergillus and radial growth of P.
      cinnamomi. A commercial preparation of phenol-2,4-bis (1,1-dimethylethyl) caused
      the same effects on mycelium morphology and radial growth as our isolate,
      confirming the presence of this compound in the root extracts. This is the first
      report of the induction of this compound in plants by SA, and the results suggest
      that it plays an important role in the defense response of avocado.

PMID- 23948675
TI  - Nonlinear simultaneous reconstruction of inhomogeneous compressibility and mass
      density distributions in unidirectional pulse-echo ultrasound imaging.
AB  - In diagnostic ultrasound imaging, the image reconstruction quality is crucial for
      reliable diagnosis. Applying reconstruction algorithms based on the acoustic wave
      equation, the obtained image quality depends significantly on the physical
      material parameters accounted for in the equation. In this contribution, we
      extend a proposed iterative nonlinear one-parameter compressibility
      reconstruction algorithm by the additional reconstruction of the object's
      inhomogeneous mass density distribution. The improved iterative algorithm is able
      to reconstruct inhomogeneous maps of the object's compressibility and mass
      density simultaneously using only one conventional linear transducer array at a
      fixed location for wave transmission and detection. The derived approach is based
      on an acoustic wave equation including spatial compressibility and mass density
      variations, and utilizes the Kaczmarz method for iterative material parameter
      reconstruction. We validate our algorithm numerically for an unidirectional pulse
      echo breast imaging application, and thus generate simulated measurements
      acquired from a numerical breast phantom with realistic compressibility and mass
      density values. Applying these measurements, we demonstrate with two
      reconstruction experiments the necessity to calculate the mass density in case of
      tissues with significant mass density inhomogeneities. When reconstructing
      spatial mass density variations, artefacts in the breast's compressibility image
      are reduced resulting in improved spatial resolution. Furthermore, the
      compressibility relative error magnitude within a diagnostically significant
      region of interest (ROI) decreases from 3.04% to 2.62%. Moreover, a second image
      showing the breast's inhomogeneous mass density distribution is given to provide
      additional diagnostic information. In the compressibility image, a spatial
      resolution moderately higher than the classical half-wavelength limit is
      observed. 

PMID- 23948673
TI  - Cocaine self-administration punished by i.v. histamine in rat models of high and
      low drug abuse vulnerability: effects of saccharin preference, impulsivity, and
      sex.
AB  - A key feature of substance use disorders is continued drug consumption despite
      aversive consequences. This has been modeled in the animal laboratory by pairing
      drug self-administration with electric shock, thereby punishing drug intake
      (Deroche-Gamonet et al. 2004). In the present experiments, we examined the
      effects of punishment on i.v. cocaine self-administration by adding histamine to
      the cocaine solution with three different animal models of high and low
      vulnerability to drug abuse: rats selectively bred for high (HiS) and low (LoS)
      saccharin consumption, rats selected for high (HiI) and low (LoI) impulsivity,
      and sex differences. Animals were allowed to self-administer cocaine (0.4
      mg/kg/infusion) to establish a baseline of operant responding. Histamine
      (4.0mg/kg/infusion) was then added directly into the cocaine solution and its
      consequent effects on self-administration were compared to baseline. The
      histamine+cocaine solution was then replaced with a cocaine-only solution, and
      the rats' operant responding was again compared to baseline. Concurrent histamine
      exposure was effective in reducing cocaine consumption in all groups of rats;
      however, LoS and female rats took longer to return to baseline levels of cocaine
      consumption after histamine was removed compared to HiS and male rats. These data
      suggest that the reduction of drug self-administration by aversive consequences
      may differ in groups that vary in drug use vulnerability . Such results may
      inform pharmacological strategies that enhance the negative aspects of drug
      consumption.

PMID- 23948676
TI  - Imaging recommendations for acute stroke and transient ischemic attack patients:
      a joint statement by the American Society of Neuroradiology, the American College
      of Radiology and the Society of NeuroInterventional Surgery.
AB  - In the article entitled "Imaging Recommendations for Acute Stroke and Transient
      Ischemic Attack Patients: A Joint Statement by the American Society of
      Neuroradiology, the American College of Radiology and the Society of
      NeuroInterventional Surgery", we are proposing a simple, pragmatic approach that
      will allow the reader to develop an optimal imaging algorithm for stroke patients
      at their institution. 

PMID- 23948677
TI  - Added value of trabecular bone score to bone mineral density for prediction of
      osteoporotic fractures in postmenopausal women: the OPUS study.
AB  - The objective of this study was to consider whether trabecular bone score (TBS)
      improves on areal bone mineral density (aBMD) measurement alone for the
      prediction of incident fractures in postmenopausal women. PATIENTS AND METHODS:
      The OPUS study was conducted in ambulatory European women aged above 55years,
      recruited in 5 centers followed over 6years. For the assessment of the
      performance of TBS, baseline Hologic scans from 3 centers (Kiel, Paris and
      Sheffield) were available. Follow-up for incident fractures was available for
      1007 women (mean age 65.9+/-6.9years). We compared the performance of TBS, aBMD,
      and their combination, by using net reclassification improvement (NRI, primary
      analysis) and receiver operator characteristic (ROC) c-statistical analysis with
      ORs and areas under the curves (AUCs) (secondary analyses). RESULTS: 82 (8.1%)
      subjects with incident clinical osteoporotic fractures, and 46 (4.6%) with
      incident radiographic vertebral fractures were recorded over 6years. Performance
      of TBS was significantly better than lumbar spine (LS) aBMD for the prediction of
      incident clinical osteoporotic fractures (NRI=16.3%, p=0.007). For radiographic
      vertebral fractures, TBS and LS aBMD had similar predictive power but the
      combination of TBS and LS aBMD increased the performance over LS aBMD alone
      (NRI=8.6%, p=0.046) but the prediction is similar to hip and femoral neck aBMD.
      In non osteoporotic women, TBS predicted incident fragility fractures similarly
      to LS aBMD. CONCLUSIONS: This prospective study shows that in general population,
      TBS is a useful tool to improve the performance of lumbar spine aBMD for
      vertebral osteoporotic fractures.

PMID- 23948678
TI  - A novel mutation outside homeodomain of HOXD13 causes synpolydactyly in a Chinese
      family.
AB  - INTRODUCTION: Human synpolydactyly (SPD), belonging to syndactyly (SD) II, is
      caused by mutations in homeobox d13 (HOXD13). Here, we describe the study of a
      two-generation Chinese family with a variant form of synpolydactyly. MATERIALS
      AND METHODS: The sequence of the HOXD13 gene was analyzed. Luciferase assays were
      conducted to determine whether the mutation affected the function of the HOXD13
      protein. RESULTS: We identified a novel c.659G>C (p.Gly220Ala) mutation outside
      the HOXD13 homeodomain responsible for the disease in this family. This mutation
      was not found in any of the unaffected family members and healthy control.
      Luciferase assays demonstrated that this mutation affected the transcriptional
      activation ability of HOXD13 (only approximately 84.7% of wild type, p<0.05).
      CONCLUSION: Phenotypes displayed by individuals carrying the novel mutation
      present additional features, such as the fifth finger clinodactyly, which is not
      always associated with canonical SPD. This finding enhances our understanding
      about the phenotypic spectrum associated with HOXD13 mutations and advances our
      understanding of human limb development.

PMID- 23948679
TI  - Prologue.

PMID- 23948680
TI  - The epidemiology of cerebral palsy: new perspectives from a Canadian registry.

PMID- 23948681
TI  - Brain development in infants born preterm: looking beyond injury.
AB  - Infants born very preterm are high risk for acquired brain injury and
      disturbances in brain maturation. Although survival rates for preterm infants
      have increased in the last decades owing to improved neonatal intensive care,
      motor disabilities including cerebral palsy persist, and impairments in
      cognitive, language, social, and executive functions have not decreased. Evidence
      from neuroimaging studies exploring brain structure, function, and metabolism has
      indicated abnormalities in the brain development trajectory of very preterm-born
      infants that persist through to adulthood. In this chapter, we review
      neuroimaging approaches for the identification of brain injury in the preterm
      neonate. Advances in medical imaging and availability of specialized equipment
      necessary to scan infants have facilitated the feasibility of conducting
      longitudinal studies to provide greater understanding of early brain injury and
      atypical brain development and their effects on neurodevelopmental outcome.
      Improved understanding of the risk factors for acquired brain injury and
      associated factors that affect brain development in this population is setting
      the stage for improving the brain health of children born preterm. 

PMID- 23948682
TI  - Evidence for therapeutic intervention in the prevention of cerebral palsy: hope
      from animal model research.
AB  - Knowledge translation, as defined by the Canadian Institute of Health Research,
      is defined as the exchange, synthesis, and ethically sound application of
      knowledge--within a complex system of interactions among researchers and users-
      to accelerate the capture of the benefits of research through improved health,
      more effective services and products, and a strengthened healthcare system. The
      requirement for this to occur lies in the ability to continue to determine
      mechanistic actions at the molecular level, to understand how they fit at the in
      vitro and in vivo levels, and for disease states, to determine their safety,
      efficacy, and long-term potential at the preclinical animal model level. In this
      regard, particularly as it relates to long-term disabilities such as cerebral
      palsy that begin in utero, but only express their full effect in adulthood,
      animal models must be used to understand and rapidly evaluate mechanisms of
      injury and therapeutic interventions. In this review, we hope to provide the
      reader with a background of animal data upon which therapeutic interventions for
      the prevention and treatment of cerebral palsy, benefit this community, and
      increasingly do so in the future.

PMID- 23948683
TI  - Motor measures: a moving target?
AB  - Outcome measures may be used for a variety of reasons by clinicians and
      researchers. This paper provides an overview on motor measures that can be used
      in research or practice and are classified within the International
      Classification of Functioning, Disability and Health or ICF. Specifically, body
      function measures of neuromusculoskeletal and movement-related functions are
      presented, as are mobility measures within the activity and participation domain
      of the ICF. Descriptions of measures within these categories and their
      psychometric properties are provided. Current challenges and future directions
      for motor measurement are delineated. 

PMID- 23948684
TI  - Intensive upper extremity training for children with hemiplegia: from science to
      practice.
AB  - For children with hemiplegic cerebral palsy, bimanual abilities are central to
      independent function. Over the last decade, considerable attention has been given
      to 2 forms of extended practice therapy for the upper limb, constraint-induced
      movement therapy and intensive bimanual training. This article reviews the
      varying nature of these 2 approaches and the existing scientific rationale
      supporting them. Comparisons between these 2 intensive upper extremity training
      approaches indicate similar improvements in unimanual capacity and bimanual
      performance outcomes; however, when considering participant and caregiver goal
      achievement, evidence favors a bimanual approach. Careful selection of either
      therapy for this population requires consideration of individual and contextual
      factors in relation to treatment goals. The key ingredients and dose responses
      remain unknown. Treatment intensity, intrinsic motivation, and individualization
      of treatment are hypothesized as requisite in either approach. 

PMID- 23948685
TI  - Training to enhance walking in children with cerebral palsy: are we missing the
      window of opportunity?
AB  - The objective of this paper is to (1) identify from the literature a potential
      critical period for the maturation of the corticospinal tract (CST) and (2)
      report pilot data on an intensive, activity-based therapy applied during this
      period, in children with lesions to the CST. The best estimate of the CST
      critical period for the legs is when the child is younger than 2 years of age.
      Previous interventions for walking in children with CST damage were mainly
      applied after this age. Our preliminary results with training children younger
      than 2 years showed improvements in walking that exceeded all previous reports.
      Further, we refined techniques for measuring motor and sensory pathways to and
      from the legs, so that changes can be measured at this young age. Previous
      activity-based therapies may have been applied too late in development. A
      randomized controlled trial is now underway to determine if intensive leg therapy
      improves the outcome of children with early stroke. 

PMID- 23948686
TI  - Can noninvasive brain stimulation measure and modulate developmental plasticity
      to improve function in stroke-induced cerebral palsy?
AB  - The permanent nature of motor deficits is a consistent cornerstone of cerebral
      palsy definitions. Such pessimism is disheartening to children, families, and
      researchers alike and may no longer be appropriate for it ignores the fantastic
      plastic potential of the developing brain. Perinatal stroke is presented as the
      ideal human model of developmental neuroplasticity following distinct, well
      defined, focal perinatal brain injury. Elegant animal models are merging with
      human applied technology methods, including noninvasive brain stimulation for
      increasingly sophisticated models of plastic motor development following
      perinatal stroke. In this article, how potential central therapeutic targets are
      identified and potentially modulated to enhance motor function within these
      models is discussed. Also, future directions and emerging clinical trials are
      reviewed. 

PMID- 23948687
TI  - Interactive computer play as "motor therapy" for individuals with cerebral palsy.
AB  - The aim of the study was to evaluate the quality of evidence for interactive
      computer play (ICP) to improve motor performance (including motor control,
      strength, or cardiovascular [CVS] fitness) in individuals with cerebral palsy. A
      computer-assisted literature search was completed, focusing on ICP as a
      therapeutic modality to improve motor outcomes in individuals of all ages with
      cerebral palsy with a specific focus on upper and lower extremity motor outcomes
      and promotion of CVS fitness. Articles were classified according to American
      Academy of Neurology guidelines and recommendation classifications were given
      based on the levels of evidence. Seventeen articles underwent full-text review
      including 6 on upper extremity motor function, 5 on lower extremity motor
      function, 1 on CVS fitness, and 5 on studies with a combination of upper or lower
      extremity or CVS fitness focus or both. Overall, there was level B (probable)
      evidence for ICP interventions to improve lower extremity motor control or
      function. However, there was inadequate evidence (level U) for ICP interventions
      improving upper limb motor control or function or CVS fitness. Although promising
      trends are apparent, the strongest level of evidence exists for the use of ICP to
      improve gross motor outcomes. Additional evidence is warranted especially when
      evaluating the effect of ICP on upper limb motor outcomes and CVS fitness. 

PMID- 23948688
TI  - Robot-assisted and computer-enhanced therapies for children with cerebral palsy:
      current state and clinical implementation.
AB  - The field of pediatric neurorehabilitation has rapidly evolved with the
      introduction of technological advancements over recent years. Rehabilitation
      robotics and computer-assisted systems can complement conventional
      physiotherapeutics or occupational therapies. These systems appear promising,
      especially in children, where exciting and challenging virtual reality scenarios
      could increase motivation to train intensely in a playful therapeutic
      environment. Despite promising experience and a large acceptance by the patients
      and parents, so far, only a few therapy systems have been evaluated in children,
      and well-designed randomized controlled studies in this field are still lacking.
      This narrative review aims to provide an overview about the to-date robot
      assisted and computer-based therapies and the current level of evidence and to
      share the authors experience about the clinical implication of these new
      technologies available for children with cerebral palsy. 

PMID- 23948689
TI  - The potential for stem cells in cerebral palsy--piecing together the puzzle.
AB  - The substantial socioeconomic burden of a diagnosis of cerebral palsy, coupled
      with a positive anecdotal and media spin on stem cell treatments, drives many
      affected families to seek information and treatment outside of the current
      clinical and scientific realm. Preclinical studies using several types of stem
      and adult cells--including mesenchymal stem cells, neural precursor cells,
      olfactory ensheathing glia and Schwann cells--have demonstrated some regenerative
      and functional efficacy in neurologic paradigms. This paper describes the most
      common cell types investigated for transplant in vivo and summarizes the current
      state of early-phase clinical trials. It investigates the most relevant and
      promising coadministered therapies, including rehabilitation, drug targeting,
      magnetic stimulation, and bioengineering approaches. We highlight the need for
      adjunctive combinatorial strategies to successfully transfer stem cell treatments
      from bench to bedside.

PMID- 23948690
TI  - Perspectives of young adults with cerebral palsy on transitioning from pediatric
      to adult healthcare systems.
AB  - Transition from pediatric to adult healthcare is a well-established challenge for
      individuals with neurodevelopmental disorders like cerebral palsy. With regard to
      ethics, some of the key aspects to explore include the following: if and how
      individuals feel respected during the transition process; if and how their values
      and preferences are developed and integrated within transition; and if and how
      young patients are prepared to participate in decision making (to be autonomous)
      within the transition. We carried out a qualitative study on 14 young adults with
      cerebral palsy. Some participants reported positive experiences. However, several
      tension points were identified, including before the transition (eg, transition
      envisaged with fear and apprehension); during the transition (eg, lack of
      cooperation or communication between providers in the pediatric and adult
      healthcare systems); and after the transition (eg, feelings of abandonment). We
      discuss the clinical influence and ethical significance of better capturing
      ethical values within the transition process and preparing young individuals to
      engage in discussions about their health and disease management. 

PMID- 23948691
TI  - Three-dimensional culture of sebaceous gland cells revealing the role of
      prostaglandin E2-induced activation of canonical Wnt signaling.
AB  - BACKGROUND: Prostaglandin E2 (PGE2) is a proinflammatory mediator and activates
      the canonical Wnt-beta-catenin signaling pathway in hematopoietic stem cells. The
      SZ95 cell line was established from human sebaceous gland cells and is studied as
      a model system for these cells. Given that 2D culture of SZ95 cells does not
      recapitulate the organization of sebaceous glands in situ, we developed a 3D
      culture system for these cells and examined the effects of PGE2 on cell
      morphology and function. RESULTS: SZ95 cells maintained in 3D culture formed
      organoids that mimicked the organization of sebaceous glands in situ, including
      the establishment of a basement membrane. Organoids exposed to PGE2 were larger
      and adopted a more complex organization compared with control organoids. PGE2
      activated the canonical Wnt signaling pathway as well as increased cell viability
      and proliferation, mitochondrial metabolism, and lipid synthesis in the
      organoids. CONCLUSIONS: Culture of SZ95 cells in 3D culture system recapitulates
      the structure and susceptibility to PGE2 of sebaceous glands in situ and should
      prove useful for studies of the response of these glands to inflammation and
      other environmental stressors. Our results also implicate PGE2-induced activation
      of canonical Wnt signaling pathway in regulation of the morphology,proliferation,
      and function of "semi-vivo" sebaceous glands.

PMID- 23948692
TI  - The immunologic profile of adoptively transferred lymphocytes influences stroke
      outcome of recipients.
AB  - Animals that have myelin basic protein (MBP) specific lymphocytes with a Th1(+)
      phenotype have worse stroke outcome than those that do not. Whether these MBP
      specific cells contribute to worsened outcome or are merely a consequence of
      worse outcome is unclear. In these experiments, lymphocytes were obtained from
      donor animals one month after stroke and transferred to naive recipient animals
      at the time of cerebral ischemia. The MBP specific phenotype of donor cells was
      determined prior to transfer. Animals that received either MBP specific Th1(+) or
      Th17(+) cells experienced worse neurological outcome, and the degree of
      impairment correlated with the robustness of MBP specific Th1(+) and Th17(+)
      responses. These data demonstrate that the immunologic phenotype of antigen
      specific lymphocytes influences stroke outcome. 

PMID- 23948693
TI  - Health significance of fat quality in the diet.
AB  - This paper summarizes three presentations on the global and Latin American
      perspectives on the health significance of fat quality in the diet given at the
      16th Congress of the Society of Latin American Nutrition in Havana, Cuba,
      November 11-16, 2012. Dietary fat quality contributes to the risk of the leading
      chronic diseases and is more important than fat quantity in reducing the risk of
      chronic disease mortality, especially from cardiovascular disease (CVD). In many
      countries, the consumption of saturated fats exceeds the recommended limit of 10%
      energy (%E) and intakes of polyunsaturated fats (PUFAs) are often below the
      recommended range of 6-11%E. Consumption of long-chain omega-3 PUFAs is
      especially low. In many Latin American countries, high consumption of
      carbohydrates, especially sugars, contributes to obesity, diabetes, hypertension
      and CVD, while intakes of total fat and PUFAs may be low. Thus, dietary fat
      recommendations must consider the dietary fat patterns of each country. Nutrition
      counseling can be effective in teaching individuals and families to modify their
      food intake patterns and control the major risk factors for chronic disease. 

PMID- 23948694
TI  - Epithelial expression of extracellular matrix metalloproteinase inducer/CD147 and
      matrix metalloproteinase-2 in neoplasms and precursor lesions derived from
      cutaneous squamous cells: An immunohistochemical study.
AB  - Extracellular matrix metalloproteinase inducer (CD147) is a transmembrane
      glycoprotein involved in the regulation of matrix metalloproteinases (MMPs). The
      study investigated CD147 and MMP-2 expression in epidermis of cutaneous squamous
      lesions. CD147 and MMP-2 expressions were evaluated immunohistochemically in 44
      specimens: 18 actinic keratoses (AK), 6 squamous cell carcinomas in situ (SCCIS),
      13 squamous cell carcinomas (SCC; peritumoral and invasive portions assessed),
      and 7 normal skins. Patterns of expression were assessed, with MMP-2 in nuclei
      (MMP-2n) and cytoplasm (MMP-2c) evaluated separately. The expression of each
      marker was quantified using a calculated immunohistochemical/histologic score (H
      score). Correlations were analyzed for the marker H-scores in each study group.
      Associations between H-scores and histopathologic parameters were also evaluated.
      CD147 H-score was the highest in SCC (invasive islands), followed by AK, SCCIS,
      and control specimens, respectively. MMP-2n and MMP-2c H-scores were the highest
      in AK, followed by SCCIS, SCC, and control specimens, respectively. MMP-2c and
      MMP-2n H-scores were significantly higher in peritumoral epidermis than in
      invasive islands of SCC. MMP-2c and CD147 H-scores were positively correlated in
      the peritumoral SCCs. CD147 H-score was positively correlated with tumor
      differentiation in SCC. The findings suggest that overexpression of CD147 plays a
      role in the development of SCC. 

PMID- 23948695
TI  - Single-cell imaging mass spectrometry.
AB  - Single-cell imaging mass spectrometry (IMS) is a powerful technique used to map
      the distributions of endogenous biomolecules with subcellular resolution.
      Currently, secondary ion mass spectrometry is the predominant technique for
      single-cell IMS, thanks to its submicron lateral resolution and surface
      sensitivity. However, recent methodological and technological developments aimed
      at improving the spatial resolution of matrix assisted laser desorption
      ionization (MALDI) have made this technique a potential platform of single-cell
      IMS. MALDI opens the field of single-cell IMS to new possibilities, including
      single cell proteomic imaging and atmospheric pressure analyses; however,
      sensitivity is a challenge. In this report, we estimate the availability of
      proteins and lipids in a single cell and discuss strategies employed to improve
      sensitivity at the single-cell level. 

PMID- 23948696
TI  - Solexa sequencing of microRNAs on chromium metabolism in broiler chicks.
AB  - AIM: The aim of this study was to determine the effect of chromium picolinate
      (CrPic) on the differential expression of the known microRNAs (miRNAs) in broiler
      skeletal muscle. METHODS AND RESULTS: A total of 288 1-day-old male Arbor Acres
      broilers were randomly assigned to one of four dietary treatments supplemented
      with 0, 0.4, 2.0, or 10.0 mg.kg(-1) CrPic, respectively. Dietary CrPic
      supplementation at 10.0 mg.kg(-1) increased the average daily feed intake in
      broilers (p < 0.05). On day 42, the serum total protein level was highest in
      animals treated with 2.0 mg.kg(-1) (p < 0.05) and 10.0 mg.kg(-1) CrPic (p <
      0.05). Dietary supplementation with 10.0 mg.kg(-1) CrPic decreased the levels of
      serum glucose (p < 0.05) on day 42 and of serum triglyceride (p < 0.05) on days
      21 and 42. To further identify miRNAs from broiler skeletal muscles, we sequenced
      two small RNA libraries using the Solexa sequencing approach, and 57 miRNAs were
      found to be significantly differentially expressed (p < 0.05). Among them, 6
      upregulated and 2 downregulated miRNAs were validated by real-time qPCR (p <
      0.05). CONCLUSIONS: The results of the present study provide a valuable clue
      regarding the role of miRNA target genes in the mechanism of the dietary CrPic
      effect on protein synthesis in skeletal muscles of broilers.

PMID- 23948697
TI  - Comparison of speaking fundamental frequency between premenopausal women and
      postmenopausal women with and without hormone therapy.
AB  - OBJECTIVE: The purpose of this study was to investigate the speaking fundamental
      frequency (SFF) in pre- and postmenopausal women with and without hormone therapy
      (HT) and with low and high body mass index (BMI). PATIENTS AND METHODS: The SFF
      of premenopausal women with low BMI (n = 22) was compared with the SFF of
      premenopausal women with high BMI (n = 13), postmenopausal women with HT and low
      BMI (n = 35), postmenopausal women with HT and high BMI (n = 19), postmenopausal
      women without HT and with low BMI (n = 28) and postmenopausal women without HT
      and with high BMI (n = 12) using ANCOVA and post hoc tests. RESULTS: A
      significantly lower SFF of the voice was only found in postmenopausal women
      without HT and with a low BMI. CONCLUSION: The results of this study suggest that
      the menopause lowers the voice with approximately 14 Hz and that HT and adipose
      tissue (high BMI) might counteract the menopausal drop in SFF.

PMID- 23948698
TI  - Mood, mood regulation expectancies and frontal systems functioning in current
      smokers versus never-smokers in China and Australia.
AB  - Indices of mood, mood regulation expectancies and everyday executive functioning
      were examined in adult current smokers and never-smokers of both genders in
      Australia (N = 97), where anti-smoking campaigns have dramatically reduced
      smoking prevalence and acceptability, and in China (N = 222), where smoking
      prevalence and public acceptance of smoking remain high. Dependent measures
      included the Depression Anxiety Stress Scales (DASS-21), the Negative Mood
      Regulation (NMR) expectancies scale, the Frontal Systems Behavior Scale (FrSBe),
      the Fagerstrom Test for Nicotine Dependence (FTND) and the Alcohol Use Disorders
      Identification Test (AUDIT). Multivariate analyses of covariance (MANCOVAs)
      controlling for demographic and recruitment related variables revealed highly
      significant differences between current smokers and never-smokers in both
      countries such that smokers indicated worse moods and poorer functioning than
      never-smokers on all dependent measures. Chinese smokers scored significantly
      worse on all dependent measures than Australian smokers whereas Chinese and
      Australian never-smokers did not differ on any of the same measures. Although
      nicotine dependence level as measured by FTND was significantly higher in Chinese
      than Australian smokers and was significantly correlated with all other dependent
      measures, inclusion of FTND scores as another covariate in MANCOVA did not
      eliminate the highly significant differences between Chinese and Australian
      smokers. Results are interpreted in light of the relative ease of taking up and
      continuing smoking in China compared to Australia today.

PMID- 23948699
TI  - Targeting MicroRNAs for personalized cancer therapy.

PMID- 23948700
TI  - Long non-coding RNAs and human X-chromosome regulation: a coat for the active X
      chromosome.
AB  - In mammals, the genic disequilibrium between males (XY) and females (XX) is
      resolved through the inactivation of one of the X-chromosomes in females. X
      chromosome inactivation (XCI) takes place in all mammalian species, but has
      mainly been studied in the mouse model where it was shown to be controlled by the
      interplay of several long non-coding RNA (lncRNA). However, recent data point
      toward the existence of species divergences among mammals in the strategies used
      to achieve XCI. The recent discovery of XACT, a novel lncRNA that coats the
      active X-chromosome specifically in human pluripotent cells, further highlights
      the existence of human-specific mechanisms of X-chromosome regulation. Here, we
      discuss the roles of lncRNAs in defining species-specific mechanisms controlling
      X-inactivation and explore the potential role of large lncRNAs in gene
      activation. 

PMID- 23948701
TI  - Genomic parasites or symbionts? Modeling the effects of environmental pressure on
      transposition activity in asexual populations.
AB  - Transposable elements are DNA segments capable of persisting in host genomes by
      self-replication in spite of deleterious mutagenic effects. The theoretical
      dynamics of these elements within genomes has been studied extensively, and
      population genetic models predict that they can invade and maintain as a result
      of both intra-genomic and inter-individual selection in sexual species. In
      asexuals, the success of selfish DNA is more difficult to explain. However, most
      theoretical work assumes constant environment. Here, we analyze the impact of
      environmental change on the dynamics of transposition activity when horizontal
      DNA exchange is absent, based on a stochastic computational model of transposable
      element proliferation. We argue that repeated changes in the phenotypic optimum
      in a multidimensional fitness landscape may induce explosive bursts of
      transposition activity associated with faster adaptation. However, long-term
      maintenance of transposition activity is unlikely. This could contribute to the
      significant variation in the transposable element copy number among closely
      related species. 

PMID- 23948702
TI  - A new type of annular erythema with perieccrine inflammation: erythema papulatum
      centrifugum.
AB  - Erythema papulatum centrifugum (EPC) was first described in 1962 by Watanabe [Jpn
      J Dermatol 1962;72:573] as eczematous lesions extending centrifugally. To date,
      more than 150 cases have been reported, but only in the Japanese literature. A
      review of the Japanese literature including our 5 new cases reveals that EPC
      occurs in middle-aged persons, predominantly in males, as a single lesion on the
      trunk that is self-limiting but recurs frequently. Although EPC shares several
      characteristics with the superficial type of erythema annulare centrifugum or
      asymmetrical periflexural exanthema, EPC differs from erythema annulare
      centrifugum in clinical manifestation, showing annular rings composed of grouped,
      tiny papules, and in the histology of perieccrine inflammation, while it differs
      from asymmetrical periflexural exanthema by male preponderance, onset age, high
      relapse rate and unique annular configuration. We discuss EPC as compared with
      other cutaneous disorders showing annular erythema or similar histopathology and
      suggest that EPC is a distinct clinical entity.

PMID- 23948703
TI  - Minilaparoscopic radical hysterectomy for cervical cancer: multi-institutional
      experience in comparison with conventional laparoscopy.
AB  - OBJECTIVE: To analyze the preliminary experience of three gynecologic oncology
      services with minilaparoscopic radical hysterectomy (mLRH) for the treatment of
      cervical cancer and to compare perioperative outcomes with those of conventional
      laparoscopic surgery (LRH). METHODS: Prospectively collected data on consecutive
      cervical cancer patients undergoing radical hysterectomy with a laparoscopic
      approach were analyzed retrospectively. Perioperative outcomes of women
      undergoing mLRH were compared to data from control patients who had undergone LRH
      with 5-mm instruments. Adjustment for potential selection bias in surgical
      approach was made with propensity score (PS) matching. RESULTS: The study cohort
      consisted of 257 patients, 35 undergoing mLRH and 222 undergoing LRH. The two
      groups were comparable in terms of demographic and tumor characteristics. No
      significant differences were observed between groups in terms of operative time,
      blood loss, lymph node yield, amount of parametrial or vaginal cuff tissue
      removed, and percentage of intra- or postoperative complications, both in the
      entire cohort and in the PS matched group. No conversions were needed from mLRH
      to standard laparoscopy or from minilaparoscopy to open surgery. Conversion from
      standard laparoscopy to open surgery was necessary in 2 patients. A shorter
      hospital stay was observed among women who had mLRH than in those undergoing LRH
      [2 (1-10) vs 4 (1-14) days, p = 0.005]. This difference remained significant
      after PS matching. CONCLUSION: Our preliminary study suggests that in experienced
      hands minilaparoscopy is a feasible and safe technique for radical hysterectomy
      and yields results that are equivalent to those of LRH.

PMID- 23948704
TI  - Number of examined lymph nodes and nodal status assessment in
      pancreaticoduodenectomy for pancreatic adenocarcinoma.
AB  - BACKGROUND: The accuracy of the assessment of the nodal status in resected
      cephalic pancreatic adenocarcinoma (PA) depends on the number of examined lymph
      nodes (NELN). This study assesses the impact of the NELN on N staging and
      survival and propose a minimal number of examined lymph nodes (MNELN) ensuring
      reliability of the pN status determination. METHODS: 188 consecutive patients
      treated by pancreaticoduodenectomy (PD) for PA. Correlations between NELN and
      survivals of pN0 and pN1 groups and with the rate of pN1 patients were studied. A
      probability model based on the binomial law was built to estimate the MNELN able
      to detect pN1 patients with a sensitivity >= 95%. RESULTS: Overall and disease
      free 5-year survivals were 27.2% and 24.6% respectively. 135 patients (71.8%)
      were staged pN1. The median NELN was 17 (range 0-68). Overall and disease free
      survivals of pN1 patients were not related to NELN. The influence of NELN on
      survival in pN0 patients due to stage migration did not reach significance. The
      probability model showed that a MNELN of 16 nodes was required to detect pN1
      patients with a sensitivity of 95%. CONCLUSION: A MNELN of 16 is required to
      assess pN status and should be considered as a quality criterion in future
      studies and trials on PD for PA.

PMID- 23948705
TI  - New positron emission tomography derived parameters as predictive factors for
      recurrence in resected stage I non-small cell lung cancer.
AB  - BACKGROUND: The recurrence rate for stage I non-small cell lung cancer is high,
      with 20-40% of patients that relapse after surgery. The aim of this study was to
      evaluate new F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)
      derived parameters, such as standardized uptake value index (SUVindex), metabolic
      tumor volume (MTV) and total lesion glycolysis (TLG), as predictive factors for
      recurrence in resected stage I non-small cell lung cancer. METHODS: We
      retrospectively reviewed 99 resected stage I non-small cell lung cancer patients
      that were grouped by SUVindex, TLG and MTV above or below their median value.
      Disease free survival was evaluated as primary end point. RESULTS: The 5-year
      overall survival and the 5-year disease free survival rates were 62% and 73%,
      respectively. The median SUVindex, MTL and TLG were 2.73, 2.95 and 9.61,
      respectively. Patients with low SUVindex, MTV and TLG were more likely to have
      smaller tumors (p <= 0.001). Univariate analysis demonstrated that SUVindex (p =
      0.027), MTV (p = 0.014) and TLG (p = 0.006) were significantly related to
      recurrence showing a better predictive performance than SUVmax (p = 0.031). The 5
      year disease free survival rates in patients with low and high SUVindex, MTV and
      TLG were 84% and 59%, 86% and 62% and 88% and 60%, respectively. The multivariate
      analysis showed that only TLG was an independent prognostic factor (p = 0.014)
      with a hazard ratio of 4.782. CONCLUSION: Of the three PET-derived parameters
      evaluated, TLG seems to be the most accurate in stratifying surgically treated
      stage I non-small cell lung cancer patients according to their risk of
      recurrence.

PMID- 23948706
TI  - The human uterine smooth muscle S-nitrosoproteome fingerprint in pregnancy,
      labor, and preterm labor.
AB  - Molecular mechanisms involved in uterine quiescence during gestation and those
      responsible for induction of labor at term are incompletely known. More than 10%
      of babies born worldwide are premature and 1,000,000 die annually. Preterm labor
      results in preterm delivery in 50% of cases in the United States explaining 75%
      of fetal morbidity and mortality. There is no Food and Drug Administration
      approved treatment to prevent preterm delivery. Nitric oxide-mediated relaxation
      of human uterine smooth muscle is independent of global elevation of cGMP
      following activation of soluble guanylyl cyclase. S-nitrosation is a likely
      mechanism to explain cGMP-independent relaxation to nitric oxide and may reveal S
      nitrosated proteins as new therapeutic targets for the treatment of preterm
      labor. Employing S-nitrosoglutathione as an nitric oxide donor, we identified 110
      proteins that are S-nitrosated in 1 or more states of human pregnancy. Using area
      under the curve of extracted ion chromatograms as well as normalized spectral
      counts to quantify relative expression levels for 62 of these proteins, we show
      that 26 proteins demonstrate statistically significant S-nitrosation differences
      in myometrium from spontaneously laboring preterm patients compared with
      nonlaboring patients. We identified proteins that were up-S-nitrosated as well as
      proteins that were down-S-nitrosated in preterm laboring tissues. Identification
      and relative quantification of the S-nitrosoproteome provide a fingerprint of
      proteins that can form the basis of hypothesis-directed efforts to understand the
      regulation of uterine contraction-relaxation and the development of new treatment
      for preterm labor. 

PMID- 23948707
TI  - NOX2 interacts with podocyte TRPC6 channels and contributes to their activation
      by diacylglycerol: essential role of podocin in formation of this complex.
AB  - Canonical transient receptor potential-6 (TRPC6) channels have been implicated in
      the pathophysiology of glomerular diseases. TRPC6 channels are typically
      activated by diacylglycerol (DAG) during PLC-dependent transduction cascades.
      TRPC6 channels can also be activated by reactive oxygen species (ROS). We
      previously showed that podocin is required for DAG analogs to produce robust
      activation of TRPC6 channels in podocytes. Here we show that endogenous TRPC6
      channels in immortalized podocytes reciprocally coimmunoprecipitate with the
      catalytic subunit of the NADPH oxidase NOX2 (gp91(phox)). The NOX2-TRPC6
      interaction was not detected in cells stably expressing a short hairpin RNA
      targeting podocin, although NOX2 and TRPC6 were present at normal levels.
      Application of a membrane-permeable DAG analog [1-oleoyl-2-acetyl-sn-glycerol
      (OAG)] increased generation of ROS in podocytes, but this effect was not detected
      in podocin knockdown cells. OAG also increased steady-state surface expression of
      the NOX2 regulatory subunit p47(phox). In whole cell recordings, TRPC6 activation
      by OAG was reduced in podocytes pretreated with the NOX2 inhibitor apocynin, by
      the pan-NOX inhibitor diphenylene iodonium, and by tempol, a ROS quencher.
      Cholesterol depletion and disruption of lipid rafts by methyl-beta-cyclodextrin
      reduced activation of podocyte TRPC6 channels by OAG and also eliminated the NOX2
      TRPC6 interaction as assessed by coimmunoprecipitation. These data suggest that
      active NOX2 assembles with TRPC6 at podocin-organized sterol-rich raft domains
      and becomes catalytically active in response to DAG. The localized production of
      ROS contributes to TRPC6 activation by chemical stimuli such as DAG. Podocin
      appears to be necessary for assembly of the NOX2-TRPC6 complex in lipid rafts.

PMID- 23948708
TI  - Oxygen governs Galbeta1-3GalNAc epitope in human placenta.
AB  - It is becoming increasingly apparent that the dynamics of glycans reflect the
      physiological state of cells involved in several cell functions including growth,
      response to signal molecules, migration, as well as adhesion to, interaction
      with, and recognition of other cells. The presence of glycoconjugates in human
      placenta suggests their major role in maternal-fetal exchanges, intercellular
      adhesion, cellular metabolism, and villous vessel branching. Although several
      studies have described glycoconjugate distribution in the human placenta
      descriptions of their physiological function and control mechanisms during
      placental development are lacking. In this study we investigated the
      developmental distribution and regulation of placental core 1 O- and N-glycans
      focusing on early and late first trimester human pregnancy. To define the control
      mechanisms of the oligosaccharide chains during early placentation process,
      chorionic villous explants and human trophoblast cell lines were exposed to
      various oxygen levels. We found that oxygen tension regulates changes in core-1 O
      glycan (the disaccharide Galbeta1-3GalNAc) epitope expression levels. Moreover,
      by double affinity chromatography and subsequent analysis with mass spectrometry,
      we identified in the heat shock protein 90-alpha (HSP90alpha) a good candidate as
      carrier of the Galbeta1-3GalNAc epitope at low oxygen tension. Our results
      support a fundamental role of oxygen tension in modulating glycosylation of
      proteins during placental development.

PMID- 23948709
TI  - Treatment of murine tumors using acoustic droplet vaporization-enhanced high
      intensity focused ultrasound.
AB  - High intensity focused ultrasound (HIFU) can be applied focally and noninvasively
      to thermally ablate solid tumors. Long treatment times are typically required for
      large tumors, which can expose patients to certain risks while potentially
      decreasing the therapeutic efficacy of the treatment. Acoustic droplet
      vaporization (ADV) is a promising modality that can enhance the efficacy of tumor
      treatment using HIFU. In this study, the therapeutic effects of combined HIFU and
      ADV was evaluated in mice bearing subcutaneously-implanted 4T1 tumors.
      Histological examination showed that the combination of HIFU and ADV generated a
      mean necrotic area in the tumor that was 2.9-fold larger than with HIFU alone. A
      significant enhancement of necrosis was found in the periphery of the tumor,
      where the blood supply was abundant. Seven days after treatment, the tumors
      treated with combined HIFU and ADV were 30-fold smaller in volume than tumors
      treated with HIFU alone. The study demonstrates the potential advantage of
      combining HIFU and ADV in tumor treatment. 

PMID- 23948710
TI  - Sensitive colorimetric detection of Listeria monocytogenes based on isothermal
      gene amplification and unmodified gold nanoparticles.
AB  - Listeria monocytogenes (L. monocytogenes), one of most problematic food-borne
      bacteria, is mainly transmitted through the food chain and may cause listeriosis.
      Therefore, the development of rapid and sensitive L. monocytogenes detection
      technique has become an urgent task. In this study, we proposed a method using
      hyperbranching rolling circle amplification (HRCA) combined with gold
      nanoparticle (GNP) based colorimetric strategy to offer an isothermal, highly
      sensitive and specific assay for the detection of L. monocytogenes. First, a
      linear padlock probe targeting a specific sequence in the hly gene was designed
      and followed with a ligation by Taq DNA ligase. After ligation, further
      amplification by HRCA with a thiolated primer and an unlabeled primer is
      performed. The resulting thiolated HRCA products were then captured onto GNP
      surface and made GNP more salt-tolerant. Detection of the bacteria can be
      achieved by a facilitated GNP based colorimetric testing using naked eyes.
      Through this approach, as low as 100 aM synthetic hly gene targets and about 75
      copies of L. monocytogenes can be detected. The specificity is evaluated by
      distinguishing target L. monocytogenes from other bacteria. The artificial
      contaminated food samples were also detected for its potential applications in
      real food detection. This method described here is ideal for bacteria detection
      due to its simplicity and high sensitivity. 

PMID- 23948711
TI  - Laying-up of sterile instruments in the operating theatre: equal or superior
      protection by using a horizontal unidirectional air flow system.
AB  - BACKGROUND: A system for the preparation of sterilized instruments with
      unidirectional horizontal air flow (UDHF) has several advantages over a
      unidirectional down flow system (UDDF). The advantages are based on the
      installation of the system being more flexible and easier to use, no cooling of
      the air flow being necessary and less air being needed for circulation, resulting
      in reduced energy use. OBJECTIVES: The objective of this study was to determine
      whether a system with UDHF performs equal or superior to a system with UDDF in
      terms of prevention of contamination of the air (the presence of particles and
      micro-organisms) during the laying-up process. METHODS: The degree of protection
      (DP) offered by two UDHF system variants and two UDDF system variants was
      determined for several static set-ups and a dynamic simulation of the process. In
      addition to determining the level of protection for several categories of
      particle size, colony-forming units (CFU) were also measured during process
      simulations. FINDINGS: When maximum protection (no particles present) is
      considered, the UDHF systems performed significantly better than the UDDF systems
      for particles >=2.5MUm. When particles were present, there was no significant
      difference between systems for particles >=0.3 and >=0.5MUm. However, the
      performance of the UDHF system was superior to that of the UDDF system (DP) for
      particles >=1.0MUm representing the bacteria-carrying particles. During the
      process measurements, no CFU were found with the UDDF system in 64% of the
      measurements, compared with 90% for the UDHF system (P = 0.012). CONCLUSIONS: The
      UDHF system offers equal or superior protection to the UDDF system against
      contamination of the clean area within which the laying up takes place. Despite
      our finding that the differences did not always reach statistical significance
      (due to low background concentrations), there is a clear trend, from the small
      sized particles (>=1.0MUm) up to the largest sizes considered, including bacteria
      carrying particles, that demonstrates the superiority of the horizontal flow
      system. The UDHF system offers a more robust solution than the UDDF system,
      provided that good work instructions are given and the height of the table and
      height of the plenum are properly adjusted.

PMID- 23948712
TI  - Olfactory bulb and hypothalamic acute-phase responses to influenza virus: effects
      of immunization.
AB  - BACKGROUND: Within hours of intranasal challenge, mouse-adapted H1N1 A/Puerto
      Rico/8/34 (PR8) influenza genomic RNA is found in the olfactory bulb (OB) and OB
      pro-inflammatory cytokines are up-regulated. Severing the olfactory tract delays
      the acute-phase response (APR) and the APR is attenuated by immunization.
      OBJECTIVES: To determine if immunization affects OB localization of influenza or
      the molecular brain mechanisms regulating APR. METHODS: Male mice were immunized
      with PR8 influenza, then OB viral RNA, APR, and influenza-related cytokine
      responses were determined after homologous viral challenge. RESULTS: Immunization
      did not prevent influenza OB viral invasion within 24 h of viral challenge.
      However, it greatly attenuated OB viral RNA 6 days after viral challenge and the
      APR including hypothermia and body weight loss responses. Within the OB, 24 h
      after influenza challenge, prior immunization blocked virus-induced up-regulation
      of toll-like receptor 7 and interferon (IFN) gamma mRNAs. At this time,
      hypothalamic (HT) growth hormone-releasing hormone receptor and tumor necrosis
      factor-alpha mRNAs were greatly enhanced in immunized but not in positive control
      mice. By 6 days after viral challenge, OB and HT mRNAs returned towards baseline
      values. In the lung, mRNA up-regulation was greater than that in the brain and
      maximized 6 days after challenge. Lung IFNgamma mRNA decreased at 24 h but
      increased 6 days after challenge in the positive compared to negative controls.
      Immunization prevented the up-regulation of most of the flu-related mRNAs
      measured in lungs. CONCLUSION: Collectively, these data suggest a role for OB and
      HT involvement in immunization protection against influenza infection.

PMID- 23948713
TI  - Uncarilic acid and secouncarilic acid, two new triterpenoids from Uucaria
      sessilifructus.
AB  - Two new compounds, the 6-oxo oleanane-type triterpenoid uncarilic acid, and its
      5,6-secotriterpenoid derivative, secouncarilic acid, were isolated from the hooks
      and stems of Uucaria sessilifructus together with seven known ursane-type
      triterpenoids. Uncarilic acid is the second 6-oxo oleanane-type triterpenoid ever
      reported, while secouncarilic acid is the first oleanane-type 5,6
      secotriterpenoid. A plausible biosynthetic pathway from uncarilic acid to
      secouncarilic acid was also postulated. The inhibitory activities of all the nine
      compounds against LPS-induced nitric oxide production in RAW264.7 macrophages
      were evaluated. 

PMID- 23948714
TI  - NMR study on the interaction of trehalose with lactose and its effect on the
      hydrogen bond interaction in lactose.
AB  - Trehalose, a well-known stress-protector of biomolecules, has been investigated
      for its effect on the mobility, hydration and hydrogen bond interaction of
      lactose using diffusion-ordered NMR spectroscopy and NMR of hydroxy protons. In
      ternary mixtures of trehalose, lactose and water, the two sugars have the same
      rate of diffusion. The chemical shifts, temperature coefficients, vicinal
      coupling constants and ROE of the hydroxy protons in trehalose, lactose and
      sucrose were measured for the disaccharides alone in water/acetone-d6 solutions
      as well as in mixtures. The data indicated that addition of trehalose did not
      change significantly the strength of the hydrogen bond interaction between GlcOH3
      and GalO5' in lactose. Small upfield shifts were however measured for all hydroxy
      protons when the sugar concentration was increased. The chemical shift of the
      GlcOH3 signal in lactose showed less change, attributed to the spatial proximity
      to GalO5'. Chemical exchange between hydroxy protons of lactose and trehalose was
      observed in the ROESY NMR spectra. Similar effects were observed with sucrose
      indicating no specific effect of trehalose at the concentrations investigated (73
      to 763 mg/mL) and suggesting that it is the concentration of hydroxy groups more
      than the type of sugars which is guiding intermolecular interactions.

PMID- 23948715
TI  - New evidence for early presence of hominids in North China.
AB  - The Nihewan Basin in North China has a rich source of Early Pleistocene
      Paleolithic sites. Here, we report a high-resolution magnetostratigraphic dating
      of the Shangshazui Paleolithic site that was found in the northeastern Nihewan
      Basin in 1972. The artifact layer is suggested to be located in the Matuyama
      reversed polarity chron just above the upper boundary of the Olduvai polarity
      subchron, yielding an estimated age of ca 1.7-1.6 Ma. This provides new evidence
      for hominid occupation in North China in the earliest Pleistocene. The earliest
      hominids are argued to have lived in a habitat of open grasslands mixed with
      patches of forests close to the bank of the Nihewan paleolake as indicated from
      faunal compositions. Hominid migrations to East Asia during the Early Pleistocene
      are suggested to be a consequence of increasing cooling and aridity in Africa and
      Eurasia.

PMID- 23948716
TI  - Cinchonine and thiourea.
AB  - In this viewpoint, we discuss the seminal work contributed by Dixon, who reported
      the first use of a bifunctional cinchona-derived thiourea organocatalyst for the
      enantioselective conjugate addition of malonate esters to nitroalkenes. Since
      then, this class of catalysts has been extensively utilized in a variety of
      fundamental transformations. We also highlight here some of the representative
      studies performed since the publication of this milestone work in 2005. 

PMID- 23948717
TI  - A suspension-cell biosensor for real-time determination of binding kinetics of
      protein-carbohydrate interactions on cancer cell surfaces.
AB  - A novel lectin-based suspension-cell biosensor for label-free determination of
      binding kinetics of protein-carbohydrate interactions on cancer cell surfaces
      using QCM is described. This cell-biosensor facilitates evaluation of
      glycosylation in real time on suspension cancer cell surfaces, where binding
      events take place, more closely mimicking a native environment compared with
      traditional biosensors. 

PMID- 23948718
TI  - Wetting-induced formation of controllable monodisperse multiple emulsions in
      microfluidics.
AB  - Multiple emulsions, which are widely applied in a myriad of fields because of
      their unique ability to encapsulate and protect active ingredients, are typically
      produced by sequential drop-formations and drop-encapsulations using shear
      induced emulsification. Here we report a qualitatively novel method of creating
      highly controlled multiple emulsions from lower-order emulsions. By carefully
      controlling the interfacial energies, we adjust the spreading coefficients
      between different phases to cause drops of one fluid to completely engulf other
      drops of immiscible fluids; as a result multiple emulsions are directly formed by
      simply putting preformed lower-order emulsion drops together. Our approach has
      highly controllable flexibility. We demonstrate this in preparation of both
      double and triple emulsions with a controlled number of inner drops and precisely
      adjusted shell thicknesses including ultra-thin shells. Moreover, this
      controllable drop-engulfing-drop approach has a high potential in further
      investigations and applications of microfluidics. Importantly, this innovative
      approach opens a window to exploit new phenomena occurring in fluids at the
      microscale level, which is of great significance for developing novel
      microfluidics. 

PMID- 23948719
TI  - Inflammatory pseudotumor of the lateral ventricle in a pediatric patient.
AB  - Inflammatory pseudotumor (IP) is a benign process that most commonly occurs in
      the lung and orbit. Extension into the central nervous system is extremely rare,
      and primary intraventricular lesions of the lateral ventricles are even more
      infrequent with only 2 cases reported in pediatric patients to date. Here, the
      authors present an unusual case of IP occurring in a 16-year-old female
      presenting with a 2-week history of progressive headaches and vomiting, without
      focal neurological deficits or radiographic evidence of hydrocephalus. The
      patient underwent left parietal craniotomy and complete resection of the tumor,
      with no signs of recurrence at 3-month follow-up. Although the rarity of
      intraventricular IP in pediatric patients can make its initial identification
      difficult, IP should be considered as a potential diagnosis in this population
      wherein good outcomes may be achieved following surgical resection. 

PMID- 23948720
TI  - Focused sonography of the heart, lungs, and deep veins identifies missed life
      threatening conditions in admitted patients with acute respiratory symptoms.
AB  - BACKGROUND: Patients with acute respiratory symptoms still remain a diagnostic
      challenge. The aim of the study was to evaluate whether focused sonography could
      potentially diagnose life-threatening conditions missed at the primary assessment
      in a patient population consisting of admitted patients with acute respiratory
      symptoms. METHODS: A prospective blinded observational study was conducted in a
      medical ED. Inclusion criteria were the presence of one or more of the following:
      respiratory rate > 20/min, oxygen saturation < 95%, oxygen therapy initiated,
      dyspnea, cough, or chest pain. After the initial assessment, focused sonography
      of the heart, lungs, and deep veins was performed by a physician blinded to
      patient history and the results of the primary assessment. RESULTS: One hundred
      thirty-nine patients were included. The focused sonographic examinations could be
      performed in 134 patients (96%). Focused sonography identified 19 patients (14%)
      with an acute life-threatening condition missed at the primary assessment.
      Diagnostic performance of focused sonography for the diagnosis of an acute life
      threatening condition, when using audit as gold standard, was as follows:
      sensitivity, 100% (95% CI, 85.2%-100%); specificity, 93.3% (95% CI, 86.7%-97.3%);
      positive predictive value, 76.7% (95% CI, 57.7%-90.1%); and negative predictive
      value, 100% (95% CI, 96.3%-100%). CONCLUSIONS: Focused sonography of the heart,
      lungs, and deep veins is fast, highly feasible, and able to diagnose life
      threatening conditions missed at the primary assessment in admitted patients with
      acute respiratory symptoms. In an ED setting sonography can be used both for
      ruling in and ruling out acute life-threatening conditions in these patients.

PMID- 23948721
TI  - Accurate alignment and high function after kinematically aligned TKA performed
      with generic instruments.
AB  - PURPOSE: Performing kinematically aligned total knee arthroplasty (TKA) with
      generic instruments is less costly than patient-specific instrumentation;
      however, the alignment and function with this new technique are unknown. METHODS:
      One hundred and one consecutive patients (101 knees) treated with kinematically
      aligned TKA, implanted with use of generic instruments, were prospectively
      followed. The medial collateral ligament was not released. The lateral collateral
      ligament was released in the 17 % of patients with a fixed valgus deformity. Six
      measures of alignment were categorized from a scanogram of the extremity, an
      axial scan of the knee, and an intraoperative measurement. Both the Oxford Knee
      and WOMACTM scores were assessed as function. High function was a mean Oxford
      Knee score >41. RESULTS: The frequency that patients were categorized as in-range
      was 93 % for the mechanical alignment of the limb (0 degrees  +/- 3 degrees ), 94
      % for the joint line (-3 degrees  +/- 3 degrees ), 57 % for the anatomic axis of
      the knee (-2.5 degrees  +/- -7.4 degrees  valgus), 4 % for the varus-valgus
      rotation of the tibial component (<=0 degrees  valgus), 98 % for the rotation of
      the tibial component with respect to the femoral component (0 degrees  +/- 10
      degrees ), and 94 % for the intraoperative change in the anterior-posterior
      distance of the tibia with respect to the femur at 90 degrees  of flexion (0 +/-
      2 mm). The mean OKS score was 42, and WOMACTM score was 89. For each alignment,
      the function was the same for patients categorized as an outlier or in-range.
      CONCLUSIONS: The authors prefer the use of generic instruments to perform
      kinematically aligned TKA in place of mechanically aligned TKA because five of
      six alignments were accurate and because high function was restored regardless of
      whether patients had an alignment categorized as an outlier or in-range. LEVEL OF
      EVIDENCE: IV.

PMID- 23948722
TI  - Tibial internal rotation is affected by lateral laxity in cruciate-retaining
      total knee arthroplasty: an intraoperative kinematic study using a navigation
      system and offset-type tensor.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that intraoperative
      soft-tissue balance assessed by an offset-type tensor influences post-operative
      knee kinematics after cruciate-retaining (CR) total knee arthroplasty (TKA).
      METHODS: The influence of intraoperative soft-tissue balance on knee kinematics
      in CR-TKA was retrospectively analysed in 30 patients. Intraoperative soft-tissue
      balance parameters such as varus angle (varus ligament balance), joint component
      gap (centre gap), and medial and lateral compartment gaps were measured in the
      navigation system while applying 40-lb joint distraction force at 0 degrees , 10
      degrees , 30 degrees , 60 degrees , 90 degrees , and 120 degrees  of knee flexion
      using an offset-type tensor with the patella reduced. Tibial internal rotation
      and tibial anterior translation were measured as the differences between the
      values at 60 degrees  and 120 degrees  of flexion using the navigation system.
      Correlations between the soft-tissue parameters and post-operative knee
      kinematics were analysed. RESULTS: The varus ligament balance was positively
      correlated with tibial internal rotation at 60 degrees  and 90 degrees  of
      flexion (R = 0.54, P < 0.05; R = 0.60, P < 0.01, respectively). Furthermore, the
      joint component gap was positively correlated with tibial internal rotation at 90
      degrees  of flexion (R = 0.44, P < 0.05), and the lateral compartment gap was
      positively correlated with tibial internal rotation at 60 degrees , 90 degrees ,
      and 120 degrees  of knee flexion. CONCLUSIONS: The intraoperative varus ligament
      balance and joint component gap values were factors that predicted post-operative
      knee kinematics after CR-TKA. Lateral laxity at mid-to-deep knee flexion plays a
      significant role in tibial internal rotation. LEVEL OF EVIDENCE: III.

PMID- 23948724
TI  - Overproduction of poly(beta-malic acid) (PMA) from glucose by a novel
      Aureobasidium sp. P6 strain isolated from mangrove system.
AB  - After over 100 strains of Aureobasidium spp isolated from mangrove system were
      screened for their ability to produce poly(beta-malic acid) (PMA), it was found
      that Aureobasidium sp. P6 strain among them could produce high level of Ca(2+)
      PMA. Fourteen percent glucose and 6.5 % CaCO3 in the medium were the most
      suitable for Ca(2+)-PMA production. Then, 100.7 g/l of Ca(2+)-PMA was produced
      using Aureobasidium sp. P6 strain within 168 h at flask level. During 10-l batch
      fermentation, when the medium contained 12.0 % glucose, 98.7 g/l of Ca(2+)-PMA in
      the culture and 14.7 g/l of cell dry weight were obtained within 156 h, leaving
      0.34 % reducing sugar in the fermented medium. When glucose concentration in the
      fermentation medium was 14.0 %, 118.3 g/l of Ca(2+)-PMA in the culture and 16.4
      g/l of cell dry weight were obtained within 168 h, leaving 0.4 % reducing sugar
      in the fermented medium. After purification of Ca(2+)-PMA from the culture and
      acid hydrolysis of the pure Ca(2+)-PMA, analysis of HPLC showed that
      Aureobasidium sp. P6 strain only produced two main components of Ca(2+)-PMA and
      minor amount of calcium malate and that the hydrolysate of PMA was mainly
      composed of calcium malate. This is the first time to report that the novel yeast
      strain Aureobasidium sp. P6 strain isolated from the mangrove systems can produce
      such high amount of Ca(2+)-PMA.

PMID- 23948723
TI  - Thermophilic biohydrogen production: how far are we?
AB  - Apart from being applied as an energy carrier, hydrogen is in increasing demand
      as a commodity. Currently, the majority of hydrogen (H2) is produced from fossil
      fuels, but from an environmental perspective, sustainable H2 production should be
      considered. One of the possible ways of hydrogen production is through
      fermentation, in particular, at elevated temperature, i.e. thermophilic
      biohydrogen production. This short review recapitulates the current status in
      thermophilic biohydrogen production through fermentation of commercially viable
      substrates produced from readily available renewable resources, such as
      agricultural residues. The route to commercially viable biohydrogen production is
      a multidisciplinary enterprise. Microbiological studies have pointed out certain
      desirable physiological characteristics in H2-producing microorganisms. More
      process-oriented research has identified best applicable reactor types and
      cultivation conditions. Techno-economic and life cycle analyses have identified
      key process bottlenecks with respect to economic feasibility and its
      environmental impact. The review has further identified current limitations and
      gaps in the knowledge, and also deliberates directions for future research and
      development of thermophilic biohydrogen production. 

PMID- 23948726
TI  - Depolymerization and decolorization of kraft lignin by bacterium Comamonas sp. B
      9.
AB  - There is no commercial or industrial-scale process for the remediation of black
      liquor using microorganisms to date. One of the most important causes is that
      most microorganisms are not able to use lignin as their principal metabolic
      carbon or energy source. The bacterial strain Comamonas sp. B-9 has shown
      remarkable ability to degrade kraft lignin and decolorize black liquor using
      lignin as its principal metabolic carbon and energy source. This report looks at
      the depolymerization and decolorization of kraft lignin by Comamonas sp. B-9. The
      degradation, decolorization, and total carbon removal reached 45, 54, and 47.3%,
      respectively, after 7 days treatment. Comamonas sp. B-9 was capable of
      depolymerizing kraft lignin effectively as analyzed by gel permeation
      chromatography and decolorization via degrading benzene ring structures as shown
      using Fourier transform infrared spectroscopy analysis.

PMID- 23948725
TI  - Non-coding RNAs in the development and pathogenesis of eukaryotic microbes.
AB  - RNA has long been regarded as the important intermediary in the central dogma of
      gene expression. Recently, the importance of RNAs in the regulation of gene
      expression became evident with the identification and characterization of non
      protein coding transcripts named non-coding RNAs (ncRNAs). The ncRNAs, small and
      long, are ubiquitously present in all three domains of life and are being
      recognized for their important roles in genome defense and development. Some of
      the ncRNAs have been associated with diseases, and therefore, they offer
      diagnostic and therapeutic potential. In this mini-review, we have highlighted
      some recent research on the ncRNAs identified in eukaryotic microbes, with
      special emphasis on fungi that are pathogenic to humans or plants when possible.
      It is our contention that further elucidation and understanding of ncRNAs will
      advance our understanding of the development and pathogenesis of eukaryotic
      microbes and offer alternatives in the diagnosis and treatment of the diseases
      caused by these pathogens. 

PMID- 23948727
TI  - Enhanced alpha-ketoglutaric acid production and recovery in Yarrowia lipolytica
      yeast by effective pH controlling.
AB  - The replacement of chemical synthesis by environmentally friendly energy
      efficient technologies for production of valuable metabolites is a principal
      strategy of developing biotechnological industry all over the world. In the
      present study, we develop a method for alpha-ketoglutaric acid (KGA) production
      from rapeseed oil with the use of Yarrowia lipolytica yeast. Sixty strains of Y.
      lipolytica yeasts were tested for their ability to produce KGA, and the strain Y.
      lipolytica 212 (Y. lipolytica VKM Y-2412) was selected as a promising KGA
      producer. Using a three-stage pH controlling, in which pH was 4.5 in the growth
      phase, then since 72 to 144 h, pH was maintained at 3.5 and in the later phase of
      acid production, the titration by KOH was switch off, selected strain produced
      106.5 g l(-1) of KGA with mass yield of 0.95 g g(-1). KGA in the form of
      monopotassium salt was isolated from the culture broth and purified. The
      isolation procedure involved separation of biomass, extraction of residual
      triglycerides, filtrate bleaching, and acidification with mineral acid (to pH 2.8
      3.4), concentration, precipitation of mineral salts, and crystallization of the
      product. The purity of KGA isolated from the culture filtrate reached 99.1 %. 

PMID- 23948728
TI  - Proteomic and transcriptional analyses of Arthrobotrys oligospora cell wall
      related proteins reveal complexity of fungal virulence against nematodes.
AB  - The nematode-trapping fungus Arthrobotrys oligospora is the best-studied fungus
      for understanding the interaction between fungi and nematodes. The fungus uses
      three-dimensional adhesive networks to capture nematodes and then penetrates into
      the worms through their cuticle. Here we examine the effects of fungal cell wall
      related proteins on morphogenesis and virulence of the fungi. We focused on the
      changes in its proteomic and transcriptional profiles during its transition from
      saprophytic to predatory phase. Isobaric tags for relative and absolute
      quantitation (iTRAQ) proteomics using the liquid chromatography/mass spectrometry
      (LC/MS) method revealed an extended set of virulence related proteins, such as
      adhesins and serine proteases, on the cell wall of A. oligospora. Transcription
      analyses of their coding genes revealed an important set of candidate virulence
      factors. Our analyses also show that glycosyl hydrolases likely play important
      roles in trap formation of A. oligospora. The adhesins on the three-dimensional
      adhesive networks may have two functions: to enable the mycelia to stick to
      nematodes and to serve as important constituents of the extracellular matrix that
      harbors many secreted virulence related proteins. This study is the first to
      systematically identify cell wall related proteins that are important in the trap
      formation and infection of the fungus against nematode hosts. 

PMID- 23948729
TI  - Effect of the timing of acetylcholinesterase inhibitor ingestion on sleep.
AB  - Many patients with Alzheimer's disease experience sleep disturbances, and
      donepezil is usually prescribed for night-time administration. However, increased
      acetylcholine is associated with cortical arousal. We evaluated whether
      subjective sleep quality differed according to the timing of medication
      administration. Ninety-two patients with mild to moderate Alzheimer's disease who
      had taken donepezil at night (n=54) or galantamine in the morning (n=38) were
      recruited for this study. Scores on the sleep visual analogue scale (VAS) for
      sleep quality and daytime drowsiness were obtained. The mean sleep-quality and
      daytime-drowsiness VAS scores of the donepezil and galantamine groups differed
      significantly at baseline (44.0+/-26.4 vs. 55.2+/-27.3, respectively; P<0.001 and
      48.8+/-28.8 vs. 38.8+/-25.3, respectively; P<0.001). The patients taking
      donepezil were then randomly assigned to take donepezil in the morning (n=24) or
      at night (n=30). Eight weeks later, VAS scores also differed among the three
      groups (P<0.001 for both sleep quality and daytime drowsiness). The VAS scores of
      patients taking galantamine and donepezil in the morning were different from
      those taking donepezil at night at week 8. Significant changes in VAS scores
      emerged only in the group taking donepezil in the morning (4.6+/-26.5, P=0.046
      for sleep quality; -7.1+/-26.1, P<0.001 for daytime drowsiness). These results
      suggest that taking acetylcholinesterase inhibitors in the morning can improve
      the sleep states of patients with Alzheimer's disease. 

PMID- 23948730
TI  - Experimental characterization of two-dimensional pencil beam scanning proton spot
      profiles.
AB  - Dose calculations of pencil beam scanning treatment plans rely on the accuracy of
      proton spot profiles; not only the primary component but also the broad tail
      components. Four films are placed at several locations in air and multiple depths
      in Solidwater(r) for six selected energies. The films used for the primary
      components are exposed to 50-200 MU to avoid saturation; the films used for the
      tail components are exposed to 800, 8000 and 80,000 MU. By applying a
      pair/magnification method and merging these data, dose kernels down to 10(-4) of
      the central spot dose can be generated. From these kernels one can calculate the
      dose-per-MU for different field sizes and shapes. Measurements agree within 1% of
      dose-kernel-based calculations for output versus field size comparisons.
      Asymmetric, comet-shaped profile tails have a bigger impact at superficial depths
      and low energies: the output difference between two orientations at the surface
      of a rectangular field of 40 mm*200 mm is about 2% at the isocentre at 100 MeV.
      Integration of these dose kernels from 0 to 40 mm radius shows that the charge
      deficit in the Bragg peak chamber varies <2% from entrance to the end of range
      for energies <180 MeV, but exceeds 5% at 225 MeV.

PMID- 23948731
TI  - [Urticaria ... and treatment fails].
AB  - According to the guidelines the treatment goal for all types of urticaria is to
      achieve complete symptom relief. Therefore the available literature for urticaria
      treatment was reviewed regarding this aim and treatment failure, respectively.
      Systematic studies are not available. Standard doses of H1-antihistamines are the
      only approved therapy. Review of the limited data where statements are made about
      complete alleviation of symptoms shows that standard doses of H1-antihistamines
      rarely achieve this. Even when the dosage is increased up to four-fold, the
      failure rate is high. Additional therapy with montelukast, dapsone, and
      cyclosporine A also often fails to produce complete control. For severe chronic
      spontaneous urticaria, controlled studies using omalizumab have shown low failure
      rates over long time periods. It has not been investigated whether up-dosing or
      reduced injection intervals could further improve this rate. Taken together, the
      small amount of available data on complete symptom relief in urticaria treatment
      is astonishing. Moreover, the studies can not be compared due to different
      inclusion criteria (severity of urticaria, allowed basic treatment) and evaluated
      parameters. Further controlled studies are vitally needed to achieve the goal of
      complete symptom relief in urticaria. 

PMID- 23948732
TI  - Indigenous and acquired modifications in the aminoglycoside binding sites of
      Pseudomonas aeruginosa rRNAs.
AB  - Aminoglycoside antibiotics remain the drugs of choice for treatment of
      Pseudomonas aeruginosa infections, particularly for respiratory complications in
      cystic-fibrosis patients. Previous studies on other bacteria have shown that
      aminoglycosides have their primary target within the decoding region of 16S rRNA
      helix 44 with a secondary target in 23S rRNA helix 69. Here, we have mapped P.
      aeruginosa rRNAs using MALDI mass spectrometry and reverse transcriptase primer
      extension to identify nucleotide modifications that could influence
      aminoglycoside interactions. Helices 44 and 45 contain indigenous (housekeeping)
      modifications at m (4)Cm1402, m (3)U1498, m (2)G1516, m (6) 2A1518, and m (6)
      2A1519; helix 69 is modified at m (3)Psi1915, with m (5)U1939 and m (5)C1962
      modification in adjacent sequences. All modifications were close to
      stoichiometric, with the exception of m (3)Psi1915, where about 80% of rRNA
      molecules were methylated. The modification status of a virulent clinical strain
      expressing the acquired methyltransferase RmtD was altered in two important
      respects: RmtD stoichiometrically modified m (7)G1405 conferring high resistance
      to the aminoglycoside tobramycin and, in doing so, impeded one of the methylation
      reactions at C1402. Mapping the nucleotide methylations in P. aeruginosa rRNAs is
      an essential step toward understanding the architecture of the aminoglycoside
      binding sites and the rational design of improved drugs against this bacterial
      pathogen. 

PMID- 23948733
TI  - Oral, esophageal and cutaneous lichen ruber planus controlled with alitretinoin:
      case report and review of the literature.
AB  - BACKGROUND: Therapy-resistant lichen planus (LP) can be a challenging condition
      for dermatologists. There are some case reports about successful treatments with
      alitretinoin of cutaneous and oral, but not of esophageal LP. OBJECTIVE: We
      present the unique case of a patient with cutaneous, oral and esophageal LP which
      was refractory to classical treatment options (topical clobetasol propionate and
      pimecrolimus, intramuscular triamcinolone acetonide); because of systemic side
      effects the patient did not tolerate systemic acitretin dosed up to 25 mg daily.
      METHODS: Oral alitretinoin was used at a dose of 30 mg daily. RESULTS: Both oral
      and skin changes as well as dysphagia completely resolved within 4 weeks without
      any severe side effects and the drug was used for 6 months. No papules, intraoral
      striae or dysphagia recurred during the 6 months of treatment. After 4 months the
      patient relapsed with mucosal patches so that a second cycle was initiated for 6
      months where oral LP lesions resolved after 4 weeks also (with sporadic mild
      headache). CONCLUSION: Further studies are needed to better understand the impact
      of alitretinoin in LP. Our observation suggests alitretinoin as a new, well
      tolerated treatment option for esophageal LP after failed response to
      conventional treatments.

PMID- 23948734
TI  - [Keratoconus lenses: the small correction miracle].
AB  - Keratoconus is a non-inflammatory corneal disease associated with a cone-shaped
      protrusion and progressive corneal thinning. Apart from progression control and
      stabilizing interventions, correcting the optical error induced by a mostly
      highly irregular corneal surface is of paramount importance with respect to
      quality of life and ability to work. This goal can be achieved efficiently by
      contact lenses with only rare adverse conditions. This article provides a current
      overview on contact lens fitting in keratoconus and presents own associated
      results. 

PMID- 23948736
TI  - [Yellow spots within the macula].

PMID- 23948735
TI  - [Ophthalmological alterations at the initial diagnosis of HIV infection].
AB  - Acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency
      virus (HIV), is one of the most important infectious causes of death in the
      twentieth and twenty-first centuries. Ocular manifestations can appear in
      particular when the CD4 cell count is low. This article presents a case report of
      a 38-year-old homosexual man in whom HIV microangiopathy retinopathy syndrome
      (MAPS) was found during the assessment of the initial HIV diagnosis. Typical
      findings in MAPS are conjunctival and retinal vessel abnormalities, cotton wool
      spots as well as intraretinal hemorrhages. Loss of vision is a rare complication
      but MAPS shows an impairment of the immune status and is also associated with a
      higher mortality. 

PMID- 23948737
TI  - [Effectiveness of initial antibiotic therapy for treatment of contact lens
      related bacterial keratitis].
AB  - BACKGROUND: Contact lens-related microbial keratitis is a cause of potentially
      sight-threatening corneal opacification. Effective initial antimicrobial therapy
      is crucial to prevent long-term complications. This investigation was undertaken
      to test the effectiveness of current routine empirical antibiotic treatment
      regimens. METHODS/PATIENTS: All consecutive cases of contact lens-related
      keratitis presenting in the outpatient clinic of the Department of Ophthalmology
      at the Medical University of Innsbruck between January 2010 and April 2012 were
      retrospectively analyzed. RESULTS: Cultures were positive in 69 out of the 123
      cases included in the study. Culture results identified 59.4 % Gram positive
      strains, 50.7 % Gram negative strains and 7.2 % fungal strains. Mixed infections
      accounted for 29 % of cases. The combination of an aminoglycoside and a second
      generation quinolone antibiotic was the most common initial treatment regimen
      (87.8 %). In vitro this regimen was less effective compared to combinations of
      moxifloxacin and ciprofloxacin or moxifloxacin and gentamicin. CONCLUSION:
      Empirical combined regimens remain an effective treatment of contact lens-related
      keratitis. Fluoroquinolones proved to be inadequate for monotherapy.

PMID- 23948738
TI  - Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury
      in mice.
AB  - Oleanolic acid (OA) is a triterpenoids that exists widely in plants. OA is
      effective in protecting against hepatotoxicants. Whereas a low dose of OA is
      hepatoprotective, higher doses and longer-term use of OA produce liver injury.
      This study characterized OA-induced liver injury in mice. Adult C57BL/6 mice were
      given OA at doses of 0, 22.5, 45, 90, and 135 mg/kg, s.c., daily for 5 days, and
      liver injury was observed at doses of 90 mg/kg and above, as evidenced by
      increases in serum activities of alanine aminotransferase and alkaline
      phosphatase, increases in serum total bilirubin, as well as by liver
      histopathology. OA-induced cholestatic liver injury was further evidenced by
      marked increases of both unconjugated and conjugated bile acids (BAs) in serum.
      Gene and protein expression analysis suggested that livers of OA-treated mice had
      adaptive responses to prevent BA accumulation by suppressing BA biosynthetic
      enzyme genes (Cyp7a1, 8b1, 27a1, and 7b1); lowering BA uptake transporters (Ntcp
      and Oatp1b2); and increasing a BA efflux transporter (Ostbeta). OA increased the
      expression of Nrf2 and its target gene, Nqo1, but decreased the expression of
      AhR, CAR and PPARalpha along with their target genes, Cyp1a2, Cyp2b10 and
      Cyp4a10. OA had minimal effects on PXR and Cyp3a11. Taken together, the present
      study characterized OA-induced liver injury, which is associated with altered BA
      homeostasis, and alerts its toxicity potential.

PMID- 23948740
TI  - Changes in the taste and textural attributes of apples in response to climate
      change.
AB  - The effects of climate change on the taste and textural attributes of foods
      remain largely unknown, despite much public interest. On the basis of 30-40 years
      of records, we provide evidence that the taste and textural attributes of apples
      have changed as a result of recent global warming. Decreases in both acid
      concentration, fruit firmness and watercore development were observed regardless
      of the maturity index used for harvest date (e.g., calendar date, number of days
      after full bloom, peel colour and starch concentration), whereas in some cases
      the soluble-solids concentration increased; all such changes may have resulted
      from earlier blooming and higher temperatures during the maturation period. These
      results suggest that the qualities of apples in the market are undergoing long
      term changes. 

PMID- 23948739
TI  - Pregnenolone co-treatment partially restores steroidogenesis, but does not
      prevent growth inhibition and increased atresia in mouse ovarian antral follicles
      treated with mono-hydroxy methoxychlor.
AB  - Mono-hydroxy methoxychlor (mono-OH MXC) is a metabolite of the pesticide,
      methoxychlor (MXC). Although MXC is known to decrease antral follicle numbers,
      and increase follicle death in rodents, not much is known about the ovarian
      effects of mono-OH MXC. Previous studies indicate that mono-OH MXC inhibits mouse
      antral follicle growth, increases follicle death, and inhibits steroidogenesis in
      vitro. Further, previous studies indicate that CYP11A1 expression and production
      of progesterone (P4) may be the early targets of mono-OH MXC in the steroidogenic
      pathway. Thus, this study tested whether supplementing pregnenolone, the
      precursor of progesterone and the substrate for HSD3B, would prevent decreased
      steroidogenesis, inhibited follicle growth, and increased follicle atresia in
      mono-OH MXC-treated follicles. Mouse antral follicles were exposed to vehicle
      (dimethylsulfoxide), mono-OH MXC (10 MUg/mL), pregnenolone (1 MUg/mL), or mono-OH
      MXC and pregnenolone together for 96 h. Levels of P4, androstenedione (A),
      testosterone (T), estrone (E1), and 17beta-estradiol (E2) in media were
      determined, and follicles were processed for histological evaluation of atresia.
      Pregnenolone treatment alone stimulated production of all steroid hormones except
      E2. Mono-OH MXC-treated follicles had decreased sex steroids, but when given
      pregnenolone, produced levels of P4, A, T, and E1 that were comparable to those
      in vehicle-treated follicles. Pregnenolone treatment did not prevent growth
      inhibition and increased atresia in mono-OH MXC-treated follicles. Collectively,
      these data support the idea that the most upstream effect of mono-OH MXC on
      steroidogenesis is by reducing the availability of pregnenolone, and that adding
      pregnenolone may not be sufficient to prevent inhibited follicle growth and
      survival.

PMID- 23948743
TI  - Resistin-like molecule alpha enhances the proliferation and migration of aortic
      vascular smooth muscle cells.
AB  - OBJECTIVE: The mitogenic and chemotactic effects of resistin-like molecule alpha
      (RELMalpha) are thought to contribute to vascular remodeling in pulmonary
      arterial hypertension. Here we evaluate the expression of RELMalpha in
      atherosclerotic plaque and investigate its effects on the proliferation and
      migration of vascular smooth muscle cells (VSMCs). METHODS: An atherosclerotic
      model was established by feeding 4-week-old C57BL/6J ApoE-/- mice (n = 9) with a
      high-fat diet. Wild-type 4-week-old C57BL/6J (n = 9) were fed the same diet and
      were used as controls. RELMalpha expression was evaluated by immunohistochemistry
      and quantified using real-time PCR (RT-PCR). A (3)H-thymidine incorporation assay
      and the Boyden chamber assay, respectively, were used to explore the effects of
      different concentrations of RELMalpha on the proliferation and migration of
      VSMCs. RESULTS: Immunohistochemistry identified positively stained granules in
      atherosclerotic plaques. These results were confirmed by detection of RELMalpha
      mRNA using RT-PCR. We also demonstrated that in vitro exposure to RELMalpha
      significantly promoted the proliferation and migration of VSMCs in a dose-related
      manner (p < 0.01). CONCLUSIONS: RELMalpha expressed in atherosclerotic plaque of
      ApoE-/- mice appears to enhance the proliferation and migration of aortic VSMCs
      in a dose-related manner.

PMID- 23948741
TI  - Isoform- and receptor-specific channel property of canonical transient receptor
      potential (TRPC)1/4 channels.
AB  - Transient receptor potential canonical (TRPC) 1, the first mammalian homologue of
      Drosophila trp gene, is distributed widely in mammalian cells and is involved in
      many physiological functions. TRPC1 is reported to be functional following
      heteromeric formation with other TRPC channels such as TRPC4 or TRPC5. It is
      known that the composition of this widely distributed TRPC1 is far from simple;
      functionality of such channels has been highly controversial. Furthermore, TRPC1
      gene is known to have two splicing variants; one encodes long (TRPC1alpha) and
      the other encodes short (TRPC1beta) TRPC1 isoforms, respectively. In this study,
      we examined the functionality of TRPC1/4 channels using various activation
      systems. Gq/11-coupled receptor (e.g., M1 or M3 receptors) stimulation
      significantly increased TRPC1alpha/4 currents but induced mild activation of
      TRPC1beta/4. In addition, when expressed with TRPC4, TRPC1alpha acted as a pore
      constituting subunit and not a beta ancillary subunit. Multimerized with TRPC4,
      TRPC1alpha also generated strong pore field strength. We also found that Gi/o
      coupled receptor (e.g., M2 receptor) stimulation was insufficient to activate
      TRPC1alpha/4 and TRPC1beta/4 channels but selectively activated TRPC4 homomeric
      channels. These findings demonstrate that TRPC1/4 channel shows dynamic gating
      property depending on TRPC1 isoform subtypes and receptor stimulation system.
      Therefore, careful discrimination of the specificity of TRPC1 isoforms and
      upstream activation system is important in thorough understanding of TRPC1 and
      TRPC1/4 channels. 

PMID- 23948742
TI  - Ethanol and its non-oxidative metabolites profoundly inhibit CFTR function in
      pancreatic epithelial cells which is prevented by ATP supplementation.
AB  - Excessive alcohol consumption is a major cause of acute pancreatitis, but the
      mechanism involved is not well understood. Recent investigations suggest that
      pancreatic ductal epithelial cells (PDECs) help defend the pancreas from noxious
      agents such as alcohol. Because the cystic fibrosis transmembrane conductance
      regulator (CFTR) Cl(-) channel plays a major role in PDEC physiology and mutated
      CFTR is often associated with pancreatitis, we tested the hypothesis that ethanol
      affects CFTR to impair ductal function. Electrophysiological studies on native
      PDECs showed that ethanol (10 and 100 mM) increased basal, but reversibly
      blocked, forskolin-stimulated CFTR currents. The inhibitory effect of ethanol was
      mimicked by its non-oxidative metabolites, palmitoleic acid ethyl ester (POAEE)
      and palmitoleic acid (POA), but not by the oxidative metabolite, acetaldehyde.
      Ethanol, POAEE and POA markedly reduced intracellular ATP (ATPi) which was linked
      to CFTR inhibition since the inhibitory effects were almost completely abolished
      if ATPi depletion was prevented. We propose that ethanol causes functional damage
      of CFTR through an ATPi-dependent mechanism, which compromises ductal fluid
      secretion and likely contributes to the pathogenesis of acute pancreatitis. We
      suggest that the maintenance of ATPi may represent a therapeutic option in the
      treatment of the disease. 

PMID- 23948744
TI  - Health information technology can make disasters seem like business as usual.

PMID- 23948745
TI  - Being judge and jury: a new skill for emergency physicians.

PMID- 23948746
TI  - Home is where the heart is.

PMID- 23948747
TI  - Resident perspectives on professionalism lack common consensus.
AB  - STUDY OBJECTIVE: We sought to characterize and understand the residents'
      perspective on how professionalism develops through pediatric emergency medicine
      experiences. METHODS: Qualitative methods (freelisting--listing words associated
      with professionalism--and semistructured interviews) were conducted with senior
      emergency medicine and pediatric residents about their experiences rotating in
      the emergency department of a large, urban, tertiary care, freestanding
      children's hospital. All senior residents were eligible, with purposive sampling
      to maximize demographic variability. Saliency (importance) of words was analyzed
      with Smith S scores and consensus analysis. Interviews were conducted until
      content saturation was achieved; transcripts were coded by independent
      investigators to reach thematic consensus. RESULTS: Twenty-five interviews (36%
      emergency, 64% pediatrics) were conducted. Common words associated with
      professionalism were "respect," "compassion," "empathy," and "integrity";
      however, residents did not share a common consensus. The framework for how
      residents described the development of their professionalism includes
      observations, interactions, and environment. Examples include resident
      observation of role models; interactions with patients, families, and coworkers;
      self-reflection; and the unique environment of the ED. Residents believed that
      role modeling was the most influential factor. Few reported receiving sufficient
      observation by attending physicians during their interactions with patients and
      most reported receiving little direct feedback on their professionalism.
      Residents' descriptions of professionalism crossed multiple Accreditation Council
      for Graduate Medical Education (ACGME) competencies. CONCLUSION: Residents
      displayed high variability in their understanding of professionalism, which was
      frequently at variance with the corresponding ACGME competency definition. The
      resident perspective and understanding of professionalism may usefully inform
      refinements in ACGME milestones and entrustable professional activities.

PMID- 23948748
TI  - Dexmedetomidine-induced atrioventricular block followed by cardiac arrest during
      atrial pacing: a case report and review of the literature.
AB  - Sinus bradycardia is a well-known consequence of stimulation of presynaptic
      alpha2 adrenergic receptors due the adminstration of dexmedetomidine. One of the
      most serious adverse effects of dexmedetomidine is cardiac arrest. Some cases
      demonstrating such an arrest due to the indiscriminate use of this drug were
      recently reported. We continuously administered dexmedetomidine to a 56-year-old
      male patient at a rate of 0.3 MUg/kg/h (lower than the recommended dose) without
      initial dosing for sedation in an intensive care unit. The patient had undergone
      open cardiac surgery and atrial pacing was maintained at a fixed rate, 90/min.
      The PQ interval in electrocardiography gradually prolonged during the infusion;
      finally, complete atrioventricular block and subsequent cardiac arrest occurred.
      Immediate cardiopulmonary resuscitation was carried out, including re-intubation,
      and recovery of spontaneous circulation was attained 15 min after the event. The
      patient was discharged from hospital on the 25th postoperative day without any
      neurological complications.

PMID- 23948749
TI  - Molecular subtypes of serous borderline ovarian tumor show distinct expression
      patterns of benign tumor and malignant tumor-associated signatures.
AB  - Borderline ovarian tumors show heterogeneity in clinical behavior. Most have
      excellent prognosis, although a small percentage show recurrence or progressive
      disease, usually to low-grade serous carcinoma. The aim of this study was to
      understand the molecular relationship between these entities and identify
      potential markers of tumor progression and therapeutic targets. We studied gene
      expression using Affymetrix HGU133plus2 GeneChip microarrays in 3 low-grade
      serous carcinomas, 13 serous borderline tumors and 8 serous cystadenomas. An
      independent data set of 18 serous borderline tumors and 3 low-grade serous
      carcinomas was used for validation. Unsupervised clustering revealed clear
      separation of benign and malignant tumors, whereas borderline tumors showed two
      distinct groups, one clustering with benign and the other with malignant tumors.
      The segregation into benign- and malignant-like borderline molecular subtypes was
      reproducible on applying the same analysis to an independent publicly available
      data set. We identified 50 genes that separate borderline tumors into their
      subgroups. Functional enrichment analysis of genes that separate borderline
      tumors to the two subgroups highlights a cell adhesion signature for the
      malignant-like subset, with Claudins particularly prominent. This is the first
      report of molecular subtypes of borderline tumors based on gene expression
      profiling. Our results provide the basis for identification of biomarkers for the
      malignant potential of borderline ovarian tumor and potential therapeutic targets
      for low-grade serous carcinoma. 

PMID- 23948750
TI  - Phosphorylation of NTRK1 at Y674/Y675 induced by TP53-dependent repression of
      PTPN6 expression: a potential novel prognostic marker for breast cancer.
AB  - We have identified a ligand-independent mechanism whereby the tumor suppressor,
      TP53, induces nerve growth factor receptor, NTRK1, phosphorylation at Y674/Y675
      (NTRK1-pY674/pY675), via the repression of the NTRK1-phosphatase, PTPN6. This
      results in suppression of breast cancer cell proliferation. In this
      investigation, we aimed to establish whether perturbation of the wild-type TP53
      NTRK1-pY674/pY675-PTPN6 pathway has an impact on disease-free survival of breast
      cancer patients without neo-adjuvant treatment. A total of 308 tumor samples were
      stained for NTRK1, NTRK1-pY674/pY675, PTPN6, and TP53 expression. Association
      between expression levels and disease-free survival was determined by the
      univariate/multivariate and Kaplan-Meir methods of analysis. DNA from tumors was
      sequenced to identify mutant or wild-type TP53. Tumors expressing NTRK1
      pY674/pY675 but with undetectable or low levels of PTPN6 and TP53 were associated
      with prolonged 5, 10, and 15 years' disease-free survival by 48%, 36%, and 37%,
      respectively, in the multivariate analysis (P<0.05). A similar result was
      observed in tumors expressing wild-type TP53, NTRK1-pY674/pY675, and low or
      undetectable levels of PTPN6. Given that estrogen receptor-positive breast
      cancers encode wild-type TP53, we analyzed this expression pattern in these
      tumors. Multivariate analysis showed that it was significantly and independently
      predictive of prolonged survival by 66%, 70%, and 84%, respectively, (P<0.05).
      The Kaplan-Meir method demonstrated that NTRK1-pY674/pY675 together with
      undetectable or low levels of PTPN6 correlated with 59% probability of disease
      free survival (median survival 15 years), compared with 7% probability of disease
      free survival (median survival 4.5 years) when absent. In luminal A tumors, the
      presence of this pattern was estimated to have a 61% probability of disease-free
      survival (median survival 15 years), compared with 6% probability of disease-free
      survival (median survival 3 years) when it was absent. These results strongly
      suggest that expression of NTRK1-pY674/pY675 together with wild-type TP53 and low
      levels of PTPN6 expression are predictors of improved disease-free survival and
      that they could be useful biomarkers to predict clinical outcome. 

PMID- 23948751
TI  - Reversal of boswellic acid analog BA145 induced caspase dependent apoptosis by
      PI3K inhibitor LY294002 and MEK inhibitor PD98059.
AB  - PI3K/Akt and ERK pathways are important for growth and proliferation of many
      types of cancers. Therefore, PI3K inhibitor LY294002 (LY) and MEK1/2 inhibitor
      PD98059 (PD) are used to sensitize many types of cancer cell lines to
      chemotherapeutic agents, where AKT and ERK pathways are over activated. However,
      in this study, we show for the first time that PD could protect the leukemia
      cells independent of ERK pathway inhibition, besides, we also report a detailed
      mechanism for antiapoptotic effect of LY in HL-60 cells against the cytotoxicity
      induced by a boswellic acid analog BA145. Apoptosis induced by BA145 is
      accompanied by downregulation of PI3K/Akt and ERK pathways in human myelogenous
      leukemia HL-60 cells, having activating N-Ras mutation. Both LY and PD protected
      the cells against mitochondrial stress caused by BA145, and reduced the release
      of cytochrome c and consequent activation of caspase-9. LY and PD also diminished
      the activation of caspase-8 without affecting the death receptors. Besides, LY
      and PD also reversed the caspase dependent DNA damage induced by BA145. Further
      studies revealed that LY and PD significantly reversed the inhibitory effect of
      BA145 on cell cycle regulatory proteins by upregulating hyperphosphorylated
      retinoblastoma, pRB (S795) and downregulating p21 and cyclin E. More importantly,
      all these events were reversed by caspase inhibition by Z-VAD-fmk, suggesting
      that both LY and PD act at the level of caspases to diminish the apoptosis
      induced by BA145. These results indicate that inhibitors of PI3K/Akt and ERK
      pathways can play dual role and act against chemotherapeutic agents. 

PMID- 23948752
TI  - Continued declining incidence and improved survival of progressive multifocal
      leukoencephalopathy in HIV/AIDS patients in the current era.
AB  - To evaluate the situation and perspectives of progressive multifocal
      leukoencephalopathy (PML) in human immunodeficiency virus (HIV)-infected
      patients, we investigated changes in the incidence, causes, and long-term outcome
      of this disease in 72 acquired immunodeficiency syndrome (AIDS) patients who were
      diagnosed with PML from 1996 to 2011. Patients were classified according to the
      date of diagnosis in the first (1996-2000, n = 35), second (2001-2006, n = 26),
      and recent or third highly active antiretroviral therapy (HAART) period (2007
      2011, n = 11). Overall, the incidence of PML decreased from 14.8 cases/1,000
      patients/year in 1996 to 2.6 in 2005 and 0.8 in 2011, and nearly two-thirds of
      recent cases (64 %) were observed in HIV patients not attending clinical visits.
      The baseline median CD4+ count was higher in recently PML-diagnosed patients (77
      vs. 86 vs. 101 cells/mm(3); p < 0.01), and this fact was associated with a
      cerebrospinal fluid (CSF) inflammatory profile (from 11 to 31 to 55 %, p = 0.007)
      and with a significantly longer survival (attributable death, 54 vs. 35 vs. 36 %,
      respectively, p < 0.01). Thus, the overall 1-year and 3-year survival rates were
      55 and 50 %, respectively, increasing to 79 % at 1 year for patients with CD4+
      count above 100 cells/mm(3) at diagnosis. In a Cox regression analysis, an older
      age (hazard ratio, HR 0.76), a baseline CD4+ count above 100 cells/mm(3) (HR
      0.33), and a CSF inflammatory profile (HR 0.12) were significantly associated
      with a longer survival. The clinical presentation and outcome of PML in AIDS
      patients continue to change dramatically. Now, a declining incidence and long
      term survival is observed.

PMID- 23948753
TI  - Maternal and paternal factors associated with congenital syphilis in Shenzhen,
      China: a prospective cohort study.
AB  - Maternal and paternal factors create considerable obstacles to the elimination of
      congenital syphilis (CS). A clear understanding of maternal and paternal factors
      is important in order to define interventions in every community. This study
      aimed to investigate the maternal and paternal factors associated with CS. A
      prospective cohort study was conducted from April 25, 2007 to October 31, 2012 at
      the Shenzhen Center for Chronic Disease Control and Prevention (SCCDC) in China.
      We screened 279,334 pregnant women and identified 838 women with syphilis.
      Finally, a total of 360 women with syphilis were included for analysis. At the
      end of follow-up, 34 infants [9.4 %, 95 % confidence interval (CI): 6.8-12.9 %]
      were diagnosed with CS. Following adjustment for confounders, maternal history of
      syphilis [adjusted risk ratio (aRR) = 0.21], prenatal care (aRR = 0.12), and
      complete treatment (aRR = 0.22) reduced the risk of infants being infected. Every
      two-fold increase of titer of non-treponemal antibodies (aRR = 1.88), early stage
      of syphilis (aRR = 9.59), a shorter length of time between the end of the first
      treatment to childbirth (aRR = 5.39), and every week of delay in treatment (aRR =
      2.25) for maternal syphilis as well as paternal history of cocaine use (aRR =
      6.28) and positive (aRR = 3.30) or unknown (aRR = 2.79) status of syphilis
      increased the risk of infants being infected. CS also increased the risk (aRR =
      8.02) of neonatal death. Maternal and paternal factors constituted two separate
      profiles associated with CS. To become more effective, future strategies for the
      prevention of CS should be targeted to each profile.

PMID- 23948754
TI  - Colon polypectomy: a review of routine and advanced techniques.
AB  - The value of performing comprehensive screening colonoscopy with complete colon
      polypectomy is widely accepted. Colon cancer is a significant cause of worldwide
      mortality and prospective studies have proven that colonoscopic polypectomy
      reduces both the incidence and mortality related to this disease. Over the past
      few decades the array of instruments and techniques have greatly expanded to
      assist with the safe endoscopic removal of colon polyps. This article will review
      the published literature regarding efficacy and safety of standard polypectomy
      techniques such as snare polypectomy, electrocautery, and endoscopic mucosal
      resection along with newer techniques such as endoscopic submucosal dissection
      and combined laparoscopic techniques. 

PMID- 23948755
TI  - Prognostic characteristics of gastrointestinal tract NK/T-cell lymphoma: an
      analysis of 47 patients in China.
AB  - BACKGROUND: The gastrointestinal tract is the most common primary site of
      extranodal lymphomas, whereas gastrointestinal natural killer/T-cell (GINKT)
      lymphomas are relatively rare. To date, neither the prognostic characteristics
      nor the clinical features or optimal therapeutic approach for GINKT has yet been
      defined. PATIENTS AND METHODS: In this study, a retrospective analysis was
      carried out on clinical data obtained from 47 patients diagnosed with GINKT
      lymphoma between May 1999 and August 2011 at West China Hospital. RESULTS:
      Patients had a median age of 37 years. Thirty-five of the patients were men
      (74.5%). The common clinical manifestations included fever (78.7%) and abdominal
      pain (76.6%). Seventeen patients had intestinal perforation (36.2%). All patients
      showed ulcerative lesions; the most common site of involvement was the colon
      (27/47; 57.4%), followed by the jejunoileum and ileocecum (14/47; 29.8%). The
      median survival period was 2.83 (95% confidence interval, 0.27-29) months. Age,
      perforation, B syndrome, staging according to Lugano system, and surgery were
      independent prognostic risk factors for GINKT lymphoma. CONCLUSIONS: This study
      concluded that GINKT lymphoma is prone to perforation, hemorrhage, and other
      complications; moreover, the prognosis is very poor. The Lugano staging is a
      relatively suitable staging system. Surgery before perforation is a key therapy
      factor that affected prognosis. Although the roles played by chemotherapy and
      radiotherapy are unclear, combination therapy is necessary.

PMID- 23948758
TI  - FOXP3 expression is related to high Ki-67 index and poor prognosis in lymph node
      positive breast cancer patients.
AB  - BACKGROUND: Recent preclinical studies have shown that Forkhead box protein 3
      (FOXP3) is an important tumor suppressor gene. The clinical and prognostic
      implication of FOXP3 expression in breast cancer cells still remains
      controversial. METHODS: We evaluated the FOXP3 expression status of 183 patients
      who underwent curative surgery for breast cancer using the immunohistochemical
      assay of tissue microarray. RESULTS: We found FOXP3 expression in 51 out of 183
      (27.9%) surgically resected breast cancer tumors, and 33 patients were scored as
      weak positive and 18 as strong positive. FOXP3-positive tumors were associated
      with significantly higher nuclear grade, higher histologic grade and a more
      negative estrogen receptor status. The FOXP3 expression level was independently
      associated with high Ki-67 index in a logistic regression model. In the node
      positive subgroup, strong FOXP3 positivity was related to poor disease-free
      survival and disease-specific survival compared to FOXP3-negative patients,
      whereas there was no survival difference between FOXP3-negative and FOXP3-weak
      positive patients. Multivariate analysis with adjustment for patient age and
      human epidermal growth factor receptor 2 status demonstrated significantly poor
      survival of FOXP3-strong-positive patients in node-positive patients. CONCLUSION:
      Our results suggest that strong FOXP3 expression in breast cancer cells is
      associated with poor prognosis and high Ki-67 index.

PMID- 23948759
TI  - Long-term follow-up of intrauterine growth restriction: cardiovascular disorders.
AB  - In the modern world, cardiovascular disorders are the leading cause of mortality
      in developed countries, which in most cases undergo a long subclinical phase that
      can last decades before the first clinical symptoms appear. Aside from the well
      known risk factors related to lifestyle and genetics, there is growing evidence
      that in a proportion of cases, the predisposition to cardiovascular disease lies
      in prenatal life. Moreover, numerous historical cohort studies and animal models
      have shown a clear association between low birth weight and increased
      cardiovascular mortality in adulthood, including increased risk of hypertension,
      diabetes, dyslipidemia and coagulation disorders in children and adults. Besides
      premature birth, low birth weight in the majority of the cases is caused by
      intrauterine growth restriction (IUGR), which affects up to 10% of all births.
      Several clinical and experimental studies showed that IUGR fetuses present signs
      of cardiac dysfunction in utero that persist postnatally and may condition higher
      cardiovascular risk later in life. The present review discusses the importance of
      the long-term cardiovascular follow-up of the patients who suffered early or late
      IUGR in utero, particularly with regard to the long-term epidemiological studies
      in adults, prospective studies in children and the possible mechanisms that
      trigger IUGR and cardiovascular programming. Considering the high prevalence of
      IUGR and the progressing availability of intervention strategies, it is of the
      highest clinical relevance to detect cardiovascular risks as early as possible,
      to introduce timely preventive interventions and to adapt the lifestyle, in order
      to improve the long-term cardiovascular health outcome of IUGR cases.

PMID- 23948757
TI  - Improving asthma during pregnancy with dietary antioxidants: the current
      evidence.
AB  - The complication of asthma during pregnancy is associated with a number of poor
      outcomes for the mother and fetus. This may be partially driven by increased
      oxidative stress induced by the combination of asthma and pregnancy. Asthma is a
      chronic inflammatory disease of the airways associated with systemic inflammation
      and oxidative stress, which contributes to worsening asthma symptoms. Pregnancy
      alone also intensifies oxidative stress through the systemic generation of excess
      reactive oxidative species (ROS). Antioxidants combat the damaging effects of
      ROS; yet antioxidant defenses are reduced in asthma. Diet and nutrition have been
      postulated as potential factors to combat the damaging effects of asthma. In
      particular, dietary antioxidants may play a role in alleviating the heightened
      oxidative stress in asthma. Although there are some observational and
      interventional studies that have shown protective effects of antioxidants in
      asthma, assessment of antioxidants in pregnancy are limited and there are no
      antioxidant intervention studies in asthmatic pregnancies on asthma outcomes. The
      aims of this paper are to (i) review the relationships between oxidative stress
      and dietary antioxidants in adults with asthma and asthma during pregnancy, and
      (ii) provide the rationale for which dietary management strategies, specifically
      increased dietary antioxidants, might positively impact maternal asthma outcomes.
      Improving asthma control through a holistic antioxidant dietary approach might be
      valuable in reducing asthma exacerbations and improving asthma management during
      pregnancy, subsequently impacting perinatal health. 

PMID- 23948760
TI  - LC-ESI-MS/MS quantification of 4beta-hydroxycholesterol and cholesterol in plasma
      samples of limited volume.
AB  - A liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI
      MS/MS) assay was developed and qualified for analyzing 4beta-hydroxycholesterol
      and cholesterol in 5 MUl of human and mouse plasma. Stable isotope-labeled d7
      analogs of both analytes were used as internal standards and 4.2% (w/v) human
      serum albumin in phosphate-buffered saline was used as the surrogate matrix for
      preparation of calibration curves and QCs. The assay is capable of quantification
      of 4beta-hydroxycholesterol and cholesterol from 5 to 500 ng/ml and 50 to 2000
      MUg/ml, respectively, with acceptable accuracy and precision following evaluation
      of recovery of analytes, autosampler stability and potential contribution of
      chemical oxidation to the formation of 4beta-hydroxycholesterol. The final
      reconstituted solution was diluted for quantification of cholesterol typically
      present at 1000 fold higher concentration than 4beta-hydroxycholesterol in the
      same samples used for 4beta-hydroxycholesterol quantification. The successful
      quantification using a low plasma volume was achieved by quantification of total
      forms (free and conjugated) of both analytes after alkaline hydrolysis, followed
      by derivatization to form electrospray ionization-sensitive picolinyl esters,
      which upon collision-induced dissociation gave high mass precursor-product ion
      pair for selective detection by multiple reaction monitoring. In addition,
      chromatographic separation using a 16-min reversed phase gradient elution on a
      1.9 MUm particle size, C18 column, overcame interference from other isobaric
      plasma oxysterols during detection by multiple-reaction monitoring. This assay
      was compared to an orthogonal enzymatic assay for cholesterol and all samples,
      but one, provided values that were within 10% of each other. In addition, this
      assay passed the incurred sample tests for both analytes in human and mouse
      plasma samples according to reported acceptance criteria for incurred sample
      reanalysis. The quantification of both analytes permitted the determination of
      4beta-hydroxycholesterol compared to its ratio to cholesterol as an endogenous
      biomarker for CYP3A4/5 activity. The LC-ESI-MS/MS assay was also successfully
      applied to quantification of 4beta-hydroxycholesterol and cholesterol in plasma
      samples from untreated human and mice including FRGTM KO C57Bl/6 chimeric mice
      with humanized livers. The preliminary data indicated that the plasma 4beta
      hydroxycholesterol concentrations or their ratio to cholesterol from mice
      including chimeric mice were higher than those from human.

PMID- 23948761
TI  - Simultaneous determination of harmine, harmaline and their metabolites harmol and
      harmalol in beagle dog plasma by UPLC-ESI-MS/MS and its application to a
      pharmacokinetic study.
AB  - Harmine (HAR) and harmaline (HAL) were metabolized by demethylation to form
      harmol (HOL) and harmalol (HAM) both in vivo and in vitro. It has been
      demonstrated tremendous value of HAR, HAL and their metabolites in the therapy of
      Alzheimer's disease. A rapid, selective and sensitive UPLC-ESI-MS/MS method was
      firstly developed and validated for the simultaneous determination of HAR, HAL,
      HOL, and HAM in beagle dog plasma with 9-aminoacridine as the internal standard
      (IS). After protein precipitation with acetonitrile, the analytes were separated
      within 4.5 min on an ACQUITY UPLC BEH C18 column with a gradient elution system
      composed of 0.1% formic acid and acetonitrile at a flow rate of 0.4 ml/min.
      Detection was performed using multiple reactions monitoring mode under a positive
      ionization condition. The calibration curves of four analytes showed good
      linearity (r(2)>0.9959) within the tested concentration ranges. The low limit of
      quantification for HAR, HAL, HOL, and HAM were all 1.00 ng/ml. The mean accuracy
      of the analytes was within the range of 94.56-112.23%, the R.S.D. values of intra
      day and the inter-day precision were less than 6.26% and 7.51%, respectively.
      Matrix effects and extraction recoveries of the analytes from the beagle dog
      plasma were within the range of 94.48-105.77% and 89.07-101.44%, respectively.
      The validated method was successfully applied to a pharmacokinetic study of HAR,
      HAL, HOL, and HAM in beagle dogs after intravenous administration of HAR and HAL
      both of 1.0mg/kg. The main pharmacokinetic parameters of Cmax, Vd, CL, AUC and
      MRT, except Ke and t1/2 values, showed significant difference between the two
      parent drug HAR and HAL, respectively (p<0.05-0.001). Because of the different
      metabolic rate of HAR and HAL in vivo, the two metabolites, HOL and HAM,
      exhibited unique pharmacokinetic properties.

PMID- 23948762
TI  - Metabolomic assays of amoxicillin, cephapirin and ceftiofur in chicken muscle:
      application to treated chicken samples by liquid chromatography quadrupole time
      of-flight mass spectrometry.
AB  - The aim of this study was to identity metabolites and transformation products
      (TPs) in chicken muscle from amoxicillin (AMX), cephapirin (PIR) and ceftiofur
      (TIO), which are antibiotics of the beta-lactam family. Liquid chromatography
      coupled to quadrupole time-of-flight (QqTOF) mass spectrometry was utilized due
      to its high resolution, high mass accuracy and MS/MS capacity for elemental
      composition determination and structural elucidation. Amoxicilloic acid (AMA) and
      amoxicillin diketopiperazine (DKP) were found as transformation products from
      AMX. Desacetylcephapirin (DAC) was detected as a metabolite of PIR.
      Desfuroylceftiofur (DFC) and its conjugated compound with cysteine (DFC-S-Cys)
      were detected as a result of TIO in contact with chicken muscle tissue. The
      metabolites and transformation products were also monitored during the in vivo
      AMX treatment and slaughtering period. It was found that two days were enough to
      eliminate AMX and associated metabolites/transformation products after the end of
      administration. 

PMID- 23948763
TI  - Metabonomic study of biochemical changes in the rat urine induced by Pinellia
      ternata (Thunb.) Berit.
AB  - We adopted an ultra performance liquid chromatography coupled with quadrupole
      time-of-fight mass spectrometry (UPLC Q-TOF/MS) metabonomics approach to study
      metabonomic features of rats induced by orally administered Pinellia ternata
      (Thunb.) Berit. (BX). The integrated urinary MS data were analyzed via principal
      component analysis (PCA) and partial least squares-discriminant analysis (OPLS
      DA) to identify the differential metabolites. Ten potential biomarkers were
      identified within complex sample matrix of urine. The identified biomarkers
      indicated the perturbations of tryptophan, phenylacetylglycine and pantothenic
      acid metabolism in BX-induced rats. The biomarkers that were found to be changed
      with the passage of time were explained tentatively based on previous study. 

PMID- 23948764
TI  - Optimization of protein purification and characterization using Thermofluor
      screens.
AB  - The efficient large scale production of recombinant proteins depends on the
      careful conditioning of the protein as it is isolated and purified to
      homogeneity. Low protein stability leads to low purification yields as a result
      of protein degradation, precipitation and folding instability. It is often
      necessary to go through several iterations of trial-and-error to optimize the
      homogeneity, stability and solubility of the protein sample. We have set up
      Thermofluor assays to identify customized protocols for the preparation and
      characterization of individual protein constructs. We apply a two-step approach:
      we first screen for global parameters, followed by a search for protein-specific
      additives. The first screen has been designed in such a way, that it is possible
      to discern global stability trends according to pH, salt concentration, buffer
      type and concentration. The second screen contains small molecules that can
      affect the folding, aggregation state and solubility of the protein construct and
      also includes small molecules that specifically bind and stabilize proteins. The
      screens are designed to evaluate purification and storage protocols, and aim to
      provide hints to optimize these protocols. The home-made screens have been tested
      on more than 200 different protein constructs at the Sample Preparation and
      Characterization (SPC) facility at EMBL Hamburg. We describe which RT-PCR
      machines can be adapted to perform Thermofluor assays, what are the necessary
      experimental conditions to set up a screen, some leads on how to interpret the
      data and we give several examples of Thermofluor applications beyond stability
      screens. 

PMID- 23948765
TI  - An efficient and reusable "hairy" particle acid catalyst for the synthesis of 5
      hydroxymethylfurfural from dehydration of fructose in water.
AB  - Poly(4-styrenesulfonic acid) brush-grafted silica particles, synthesized by
      surface-initiated atom transfer radical polymerization, were employed as a
      reusable acid catalyst for dehydration of fructose to 5-hydroxymethylfurfural
      (HMF) in water. The particles exhibited a high activity with the HMF yield of up
      to 31%, in contrast to 26% from the corresponding free homopolymer catalyst. 

PMID- 23948766
TI  - Light propagation in structural anisotropic media in the steady-state and time
      domains.
AB  - The determination of the reduced scattering and absorption coefficients of
      structural anisotropic turbid semi-infinite media and slabs was investigated in
      the steady-state and time domains. Forward calculations were performed with a
      Monte Carlo model that considered both cylindrical scatterers aligned in
      different directions as well as scatterers that were described by a rotationally
      symmetric scattering function. Analytical solutions of the isotropic and
      anisotropic diffusion equations were applied to retrieve the optical properties.
      It was found in the steady-state and time domains that the solutions of the
      anisotropic diffusion equation have systematic errors compared to the Monte Carlo
      simulations not only for small distances from the source. However, it is shown
      that in the time domain it is possible to retrieve useful values for the optical
      properties using the isotropic and the anisotropic diffusion equations. 

PMID- 23948768
TI  - Special focus: bioinformatics.

PMID- 23948769
TI  - Causes and imaging patterns of tree-in-bud opacities.
AB  - BACKGROUND: Multiple causes for tree-in-bud (TIB) opacities have been reported.
      However, to our knowledge the relative frequencies of the causes have not been
      evaluated. The purpose of this study was to determine the relative frequency of
      causes of TIB opacities and identify patterns of disease associated with TIB
      opacities. METHODS: Cases with TIB opacities in the radiology report in 2010 were
      identified by searching the Radiology Information System. Medical records and CT
      scan examinations were reviewed for the causes of TIB opacities. Patterns of
      disease associated with TIB opacities were evaluated. RESULTS: Causes for TIB
      opacities were established in 166 of 406 (40.9%) cases. Respiratory infections
      (119 of 166, 72%) with mycobacteria (65 of 166, 39%), bacteria (44 of 166, 27%),
      viruses (four of 166, 3%), or multiple organisms (six of 166, 4%) were most
      common. Aspiration was the cause in 42 of 166 (25%). Alternating areas of normal
      lung with regions of small airways disease (TIB opacities, bronchiectasis)
      (random small airways pattern) was specific (0.92) for Mycobacterium avium
      complex infection. Nearly uniform distribution of bronchiectasis (widespread
      bronchiectasis pattern) was specific for "diseases predisposing to airway
      infection" (specificity 0.92), such as cystic fibrosis, primary ciliary
      dyskinesia, allergic bronchopulmonary aspergillosis, and immunodeficiency states.
      Consolidation and TIB opacities (bronchopneumonia pattern) were usually due to
      bacterial infection or aspiration. Dependent distribution (specificity 0.79) and
      esophageal abnormality (specificity 0.86) with TIB opacities were associated with
      aspiration. Chronicity of findings was associated with mycobacterial infection (P
      < .0001, sensitivity 0.96). Acuteness of findings was associated with bacterial
      infection (P < .001, specificity 0.87). CONCLUSIONS: TIB opacities are most often
      a manifestation of infections or aspiration. Patterns of disease can provide
      clues to the most likely diagnosis.

PMID- 23948770
TI  - Prophylactic intravesical chemotherapy to prevent bladder tumors after
      nephroureterectomy for primary upper urinary tract urothelial carcinomas: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: Intravesical recurrence after treatment of primary upper urinary
      tract urothelial carcinomas (UUT-UCs) is common. While intravesical instillation
      is widely used to prevent recurrence after transurethral resection for primary
      bladder tumors, there is still no consensus on the prophylactic capability of
      intravesical chemotherapy in preventing bladder tumor recurrence after surgery
      for UUT-UCs. METHODS: A meta-analysis of the published results of clinical trials
      was performed to compare radical surgery alone or surgery plus postoperative
      intravesical chemotherapy. The primary end point was to determine the percentage
      of patients with recurrence in the different groups. RESULTS: Our study includes
      five trials with recurrence information on 614 patients. During follow-up, 55 of
      268 (20.5%) patients who received postoperative instillation had bladder
      recurrence compared to 127 of 346 (36.7%) patients who had no adjuvant treatment-
      a decrease of 41% in the odds of recurrence with chemotherapy (odds ratio 0.48,
      95% confidence interval 0.33-0.69, p = 0.0001). No serious adverse events were
      reported. Subgroup analyses were temporarily unavailable. CONCLUSIONS:
      Postoperative intravesical chemotherapy significantly decreases the risk of
      bladder recurrence after nephroureterectomy for primary UUT-UCs. Postoperative
      intravesical instillation is considered the treatment of choice after
      nephroureterectomy.

PMID- 23948772
TI  - Reactive oxygen species generation is not different during isometric and
      lengthening contractions of mouse muscle.
AB  - Skeletal muscles can be injured by lengthening contractions, when the muscles are
      stretched while activated. Lengthening contractions produce structural damage
      that leads to the degeneration and regeneration of damaged muscle fibers by
      mechanisms that have not been fully elucidated. Reactive oxygen species (ROS)
      generated at the time of injury may initiate degenerative or regenerative
      processes. In the present study we hypothesized that lengthening contractions
      that damage the muscle would generate more ROS than isometric contractions that
      do not cause damage. To test our hypothesis, we subjected muscles of mice to
      lengthening contractions or isometric contractions and simultaneously monitored
      intracellular ROS generation with the fluorescent indicator 5-(and-6)
      chloromethyl-2',7'-dichlorodihydrofluorescein (CM-DCFH), which is oxidized by ROS
      to form the fluorescent product CM-DCF. We found that CM-DCF fluorescence was not
      different during or shortly after lengthening contractions compared with
      isometric controls, regardless of the amount of stretch and damage that occurred
      during the lengthening contractions. The only exception was that after severe
      stretches, the increase in CM-DCF fluorescence was impaired. We conclude that
      lengthening contractions that damage the muscle do not generate more ROS than
      isometric contractions that do not cause damage. The implication is that ROS
      generated at the time of injury are not the initiating signals for subsequent
      degenerative or regenerative processes.

PMID- 23948771
TI  - Antenatal betamethasone exposure is associated with lower ANG-(1-7) and increased
      ACE in the CSF of adult sheep.
AB  - Antenatal betamethasone (BM) therapy accelerates lung development in preterm
      infants but may induce early programming events with long-term cardiovascular
      consequences. To elucidate these events, we developed a model of programming
      whereby pregnant ewes are administered BM (2 doses of 0.17 mg/kg) or vehicle at
      the 80th day of gestation and offspring are delivered at term. BM-exposed (BMX)
      offspring develop elevated blood pressure; decreased baroreflex sensitivity; and
      alterations in the circulating, renal, and brain renin-angiotensin systems (RAS)
      by 6 mo of age. We compared components of the choroid plexus fourth ventricle
      (ChP4) and cerebral spinal fluid (CSF) RAS between control and BMX male offspring
      at 6 mo of age. In the choroid plexus, high-molecular-weight renin protein and
      ANG I-intact angiotensinogen were unchanged between BMX and control animals.
      Angiotensin-converting enzyme 2 (ACE2) activity was threefold higher than either
      neprilysin (NEP) or angiotensin 1-converting enzyme (ACE) in control and BMX
      animals. Moreover, all three enzymes were equally enriched by approximately 2.5
      fold in ChP4 brush-border membrane preparations. CSF ANG-(1-7) levels were
      significantly lower in BMX animals (351.8 +/- 76.8 vs. 77.5 +/- 29.7 fmol/mg; P <
      0.05) and ACE activity was significantly higher (6.6 +/- 0.5 vs. 8.9 +/- 0.5
      fmol.min(-1).ml(-1); P < 0.05), whereas ACE2 and NEP activities were below
      measurable limits. A thiol-sensitive peptidase contributed to the majority of ANG
      (1-7) metabolism in the CSF, with higher activity in BMX animals. We conclude
      that in utero BM exposure alters CSF but not ChP RAS components, resulting in
      lower ANG-(1-7) levels in exposed animals.

PMID- 23948774
TI  - Increase in parasympathetic tone by pyridostigmine prevents ventricular
      dysfunction during the onset of heart failure.
AB  - Heart failure (HF) is characterized by elevated sympathetic activity and reduced
      parasympathetic control of the heart. Experimental evidence suggests that the
      increase in parasympathetic function can be a therapeutic alternative to slow HF
      evolution. The parasympathetic neurotransmission can be improved by
      acetylcholinesterase inhibition. We investigated the long-term (4 wk) effects of
      the acetylcholinesterase inhibitor pyridostigmine on sympathovagal balance,
      cardiac remodeling, and cardiac function in the onset of HF following myocardial
      infarction. Myocardial infarction was elicited in adult male Wistar rats. After 4
      wk of pyridostigmine administration, per os, methylatropine and propranolol were
      used to evaluate the cardiac sympathovagal balance. The tachycardic response
      caused by methylatropine was considered to be the vagal tone, whereas the
      bradycardic response caused by propranolol was considered to be the sympathetic
      tone. In conscious HF rats, pyridostigmine reduced the basal heart rate,
      increased vagal, and reduced sympathetic control of heart rate. Pyridostigmine
      reduced the myocyte diameter and collagen density of the surviving left
      ventricle. Pyridostigmine also increased vascular endothelial growth factor
      protein in the left ventricle, suggesting myocardial angiogenesis. Cardiac
      function was assessed by means of the pressure-volume conductance catheter
      system. HF rats treated with pyridostigmine exhibited a higher stroke volume,
      ejection fraction, cardiac output, and contractility of the left ventricle. It
      was demonstrated that the long-term administration of pyridostigmine started
      right after coronary artery ligation augmented cardiac vagal and reduced
      sympathetic tone, attenuating cardiac remodeling and left ventricular dysfunction
      during the progression of HF in rats. 

PMID- 23948775
TI  - Alpha-adrenoceptor antagonists and chemical sympathectomy exacerbate anaphylaxis
      induced hypotension, but not portal hypertension, in anesthetized rats.
AB  - Anaphylactic shock is sometimes life-threatening, and it is accompanied by
      hepatic venoconstriction in animals, which, in part, accounts for anaphylactic
      hypotension. Roles of norepinephrine and alpha-adrenoceptor in anaphylaxis
      induced hypotension and portal hypertension were investigated in anesthetized
      ovalbumin-sensitized Sprague-Dawley rats. The sensitized rats were randomly
      allocated to the following pretreatment groups (n = 6/group): 1) control
      (nonpretreatment), 2) alpha1-adrenoceptor antagonist prazosin, 3) nonselective
      alpha-adrenoceptor antagonist phentolamine, 4) 6-hydroxydopamine-induced chemical
      sympathectomy, and 5) surgical hepatic sympathectomy. Anaphylactic shock was
      induced by an intravenous injection of the antigen. The systemic arterial
      pressure (SAP), central venous pressure (CVP), portal venous pressure (PVP), and
      portal venous blood flow (PBF) were measured, and splanchnic [Rspl: (SAP
      PVP)/PBF] and portal venous [Rpv: (PVP-CVP)/PBF] resistances were determined.
      Separately, we measured efferent hepatic sympathetic nerve activity during
      anaphylaxis. In the control group, SAP markedly decreased, followed by a gradual
      recovery toward baseline. PVP and Rpv increased 3.2- and 23.3-fold, respectively,
      after antigen. Rspl decreased immediately, but only transiently, after antigen,
      and then increased 1.5-fold later than 10 min. The alpha-adrenoceptor antagonist
      pretreatment or chemical sympathectomy inhibited the late increase in Rspl and
      the SAP recovery. Pretreatment with alpha-adrenoceptor antagonists, or either
      chemical or surgical hepatic sympathectomy, did not affect the antigen-induced
      increase in Rpv. Hepatic sympathetic nerve activity did not significantly change
      after antigen. In conclusion, alpha-adrenoceptor antagonists and chemical
      sympathectomy exacerbate anaphylaxis-induced hypotension, but not portal
      hypertension, in anesthetized rats. Hepatic sympathetic nerves are not involved
      in anaphylactic portal hypertension. 

PMID- 23948773
TI  - Contribution of nitric oxide to brachial artery vasodilation during progressive
      handgrip exercise in the elderly.
AB  - The reduction in nitric oxide (NO)-mediated vascular function with age has
      largely been determined by flow-mediated dilation (FMD). However, in light of
      recent uncertainty surrounding the NO dependency of FMD and the recognition that
      brachial artery (BA) vasodilation during handgrip exercise is predominantly NO
      mediated in the young, we sought to determine the contribution of NO to BA
      vasodilation in the elderly using the handgrip paradigm. BA vasodilation during
      progressive dynamic (1 Hz) handgrip exercise performed at 3, 6, 9, and 12 kg was
      assessed with and without NO synthase (NOS) inhibition [intra-arterial N(G)
      monomethyl-l-arginine (l-NMMA)] in seven healthy older subjects (69 +/- 2 yr).
      Handgrip exercise in the control condition evoked significant BA vasodilation at
      6 (4.7 +/- 1.4%), 9 (6.5 +/- 2.2%), and 12 kg (9.5 +/- 2.7%). NOS inhibition
      attenuated BA vasodilation, as the first measurable increase in BA diameter did
      not occur until 9 kg (4.0 +/- 1.8%), and the change in BA diameter at 12 kg was
      reduced by ~30% (5.1 +/- 2.2%), with unaltered shear rate ( CONTROL: 407 +/- 57,
      l-NMMA: 427 +/- 67 s(-1)). Although shifted downward, the slope of the
      relationship between BA diameter and shear rate during handgrip exercise was
      unchanged ( CONTROL: 0.0013 +/- 0.0004, l-NMMA: 0.0011 +/- 0.007, P = 0.6) as a
      consequence of NOS inhibition. Thus, progressive handgrip exercise in the elderly
      evokes a robust BA vasodilation, the magnitude of which was only minimally
      attenuated following NOS inhibition. This modest contribution of NO to BA
      vasodilation in the elderly supports the use of the handgrip exercise paradigm to
      assess NO-dependent vasodilation across the life span.

PMID- 23948776
TI  - Enhanced contractility in pregnancy is associated with augmented TRPC3, L-type,
      and T-type voltage-dependent calcium channel function in rat uterine radial
      artery.
AB  - In pregnancy, alpha-adrenoceptor-mediated vasoconstriction is augmented in
      uterine radial arteries and is accompanied by underlying changes in smooth muscle
      (SM) Ca(2+) activity. This study aims to determine the Ca(2+) entry channels
      associated with altered vasoconstriction in pregnancy, with the hypothesis that
      augmented vasoconstriction involves transient receptor potential canonical type-3
      (TRPC3) and L- and T-type voltage-dependent Ca(2+) channels. Immunohistochemistry
      showed TRPC3, L-type Cav1.2 (as the alpha1C subunit), T-type Cav3.1 (alpha1G),
      and Cav3.2 (alpha1H) localization to the uterine radial artery SM. Fluorescence
      intensity of TRPC3, Cav1.2, and Cav3.2 was increased, and Cav3.1 decreased in
      radial artery SM from pregnant rats. Western blot analysis confirmed increased
      TRPC3 protein expression in the radial artery from pregnant rats. Pressure
      myography incorporating pharmacological intervention to examine the role of these
      channels in uterine radial arteries showed an attenuation of phenylephrine (PE)
      induced constriction with Pyr3 {1-[4-[(2,3,3-trichloro-1-oxo-2-propen-1
      yl)amino]phenyl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid}-mediated
      TRPC3 inhibition or with nifedipine-mediated L-type channel block alone in
      vessels from pregnant rats; both effects of which were diminished in radial
      arteries from nonpregnant rats. Combined TRPC3 and L-type inhibition attenuated
      PE-induced constriction in radial arteries, and the residual vasoconstriction was
      reduced and abolished with T-type channel block with NNC 55-0396 in arteries from
      nonpregnant and pregnant rats, respectively. With SM Ca(2+) stores depleted and
      in the presence of PE, nifedipine, and NNC 55-0396, blockade of TRPC3 reversed PE
      induced constriction. These data suggest that TRPC3 channels act synergistically
      with L- and T-type channels to modulate radial artery vasoconstriction, with the
      mechanism being augmented in pregnancy. 

PMID- 23948778
TI  - Prolactin promotes normal liver growth, survival, and regeneration in rodents:
      effects on hepatic IL-6, suppressor of cytokine signaling-3, and angiogenesis.
AB  - Prolactin (PRL) is a potent liver mitogen and proangiogenic hormone. Here, we
      used hyperprolactinemic rats and PRL receptor-null mice (PRLR(-/-)) to study the
      effect of PRL on liver growth and angiogenesis before and after partial
      hepatectomy (PH). Liver-to-body weight ratio (LBW), hepatocyte and sinusoidal
      endothelial cell (SEC) proliferation, and hepatic expression of VEGF were
      measured before and after PH in hyperprolactinemic rats, generated by placing two
      anterior pituitary glands (AP) under the kidney capsule. Also, LBW and hepatic
      expression of IL-6, as well as suppressor of cytokine signaling-3 (SOCS-3), were
      evaluated in wild-type and PRLR(-/-) mice before and after PH. Hyperprolactinemia
      increased the LBW, the proliferation of hepatocytes and SECs, and VEGF hepatic
      expression. Also, liver regeneration was increased in AP-grafted rats and was
      accompanied by elevated hepatocyte and SEC proliferation, and VEGF expression
      compared with nongrafted controls. Lowering circulating PRL levels with CB-154,
      an inhibitor of AP PRL secretion, prevented AP-induced stimulation of liver
      growth. Relative to wild-type animals, PRLR(-/-) mice had smaller livers, and
      soon after PH, they displayed an approximately twofold increased mortality and
      elevated and reduced hepatic IL-6 and SOCS-3 expression, respectively. However,
      liver regeneration was improved in surviving PRLR(-/-) mice. PRL stimulates
      normal liver growth, promotes survival, and regulates liver regeneration by
      mechanisms that may include hepatic downregulation of IL-6 and upregulation of
      SOCS-3, increased hepatocyte proliferation, and angiogenesis. PRL contributes to
      physiological liver growth and has potential clinical utility for ensuring
      survival and regulating liver mass in diseases, injuries, or surgery of the
      liver.

PMID- 23948777
TI  - Transient outwardly rectifying A currents are involved in the firing rate
      response to altered CO2 in chemosensitive locus coeruleus neurons from neonatal
      rats.
AB  - The effect of hypercapnia on outwardly rectifying currents was examined in locus
      coeruleus (LC) neurons in slices from neonatal rats [postnatal day 3 (P3)-P15].
      Two outwardly rectifying currents [4-aminopyridine (4-AP)-sensitive transient
      current and tetraethyl ammonium (TEA)-sensitive sustained current] were found in
      LC neurons. 4-AP induced a membrane depolarization of 3.6 +/- 0.6 mV (n = 4),
      while TEA induced a smaller membrane depolarization of 1.2 +/- 0.3 mV (n = 4).
      Hypercapnic acidosis (HA) inhibited both currents. The maximal amplitude of the
      TEA-sensitive current was reduced by 52.1 +/- 4.5% (n = 5) in 15% CO2
      [extracellular pH (pHo) 7.00, intracellular pH (pHi) 6.96]. The maximal amplitude
      of the 4-AP-sensitive current was reduced by 34.5 +/- 3.0% (n = 6) in 15% CO2
      (pHo 7.00, pHi 6.96), by 29.4 +/- 6.8% (n = 6) in 10% CO2 (pHo 7.15, pHi 7.14),
      and increased by 29.0 +/- 6.4% (n = 6) in 2.5% CO2 (pHo 7.75, pHi 7.35). 4-AP
      completely blocked hypercapnia-induced increased firing rate, but TEA did not
      affect it. When LC neurons were exposed to HA with either pHo or pHi constant,
      the 4-AP-sensitive current was inhibited. The data show that the 4-AP-sensitive
      current (likely an A current) is inhibited by decreases in either pHo or pHi. The
      change of the A current by various levels of CO2 is correlated with the change in
      firing rate induced by CO2, implicating the 4-AP-sensitive current in
      chemosensitive signaling in LC neurons.

PMID- 23948779
TI  - An enzyme-assisted nanoparticle crosslinking approach to enhance the mechanical
      strength of peptide-based supramolecular hydrogels.
AB  - In this work we reported an enzyme-assisted nanoparticle crosslinking (EANC)
      strategy to enhance the mechanical stability of peptide-based supramolecular
      hydrogels by more than 3000 times. 

PMID- 23948780
TI  - Darwin, malthus, sussmilch, and euler: the ultimate origin of the motivation for
      the theory of natural selection.
AB  - It is fairly well known that Darwin was inspired to formulate his theory of
      natural selection by reading Thomas Malthus's Essay on the Principle of
      Population. In fact, by reading Darwin's notebooks, we can even locate one
      particular sentence which started Darwin thinking about population and selection.
      What has not been done before is to explain exactly where this sentence -
      essentially Malthus's ideas about geometric population growth - came from. In
      this essay we show that eighteenth century mathematician Leonhard Euler is
      responsible for this sentence, and in fact forms the beginning of the logical
      chain which leads to the creation of the theory of natural selection. We shall
      examine the fascinating path taken by a mathematical calculation, the many
      different lenses through which it was viewed, and the path through which it
      eventually influenced Darwin. 

PMID- 23948781
TI  - [Surgical treatment of epithelial skin tumors and their precursors].
AB  - Squamous cell carcinomas of the skin and their precursors, actinic keratosis as
      well as basal cell carcinomas are classified as non-melanocytic skin cancer and
      belong to the group of epithelial skin tumors. This tumor entity is one of the
      most common forms of malignant cancer in western countries with an incidence of
      approximately 100-170 per 100,000 inhabitants per year in Europe. In German
      speaking countries no exact numbers are available on the early forms of squamous
      cell carcinoma, actinic keratosis (carcinoma in situ); however, results from
      Great Britain show that at ages over 70 years old the prevalence of actinic
      keratosis is 34 % in men and 18 % in women. Because invasive epithelial cancer is
      very common and most commonly occurs in the head region, a safe but skin-sparing
      approach to surgical treatment is desirable. The safest procedure with respect to
      local recurrence is surgical excision with subsequent complete 3-dimensional
      histological preparation (micrographic surgery). With this method it is possible
      to excise tissue affected by tumor tissue in small steps. This facilitates defect
      coverage and leads to very good results as well as good esthetic results. The
      local recurrence rates are extremely low compared to alternative treatment
      methods, such as photodynamic therapy, topical application of imiquimod or
      cryosurgery and for the treatment of basal cell carcinoma, for example is 0.7 %.
      Dermatological operations are therefore interventions with a very high guarantee
      of tumor-free survival and functional and esthetic results.

PMID- 23948782
TI  - Cascaded two-photon nonlinearity in a one-dimensional waveguide with multiple two
      level emitters.
AB  - We propose and theoretically investigate a model to realize cascaded optical
      nonlinearity with few atoms and photons in one-dimension (1D). The optical
      nonlinearity in our system is mediated by resonant interactions of photons with
      two-level emitters, such as atoms or quantum dots in a 1D photonic waveguide.
      Multi-photon transmission in the waveguide is nonreciprocal when the emitters
      have different transition energies. Our theory provides a clear physical
      understanding of the origin of nonreciprocity in the presence of cascaded
      nonlinearity. We show how various two-photon nonlinear effects including spatial
      attraction and repulsion between photons, background fluorescence can be tuned by
      changing the number of emitters and the coupling between emitters (controlled by
      the separation). 

PMID- 23948783
TI  - Efficacy and tolerability of risperidone, yokukansan, and fluvoxamine for the
      treatment of behavioral and psychological symptoms of dementia: a blinded,
      randomized trial.
AB  - The descriptive term behavioral and psychological symptoms of dementia (BPSD) is
      used to cover a range of noncognitive disturbances including anxiety, depression,
      irritability, aggression, agitation, eating disorders, and inappropriate social
      or sexual behaviors. Behavioral and psychological symptoms of dementia are seen
      in about 90% of patients with dementia. We aimed to compare the efficacy and
      tolerability of risperidone, yokukansan, and fluvoxamine used for BPSD in elderly
      patients with dementia. Ninety inpatients with dementia according to the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria
      were investigated in Sato Hospital, Koutokukai. We conducted an 8-week, rater
      blinded, randomized trial, administering flexibly dosed risperidone, yokukansan,
      or fluvoxamine. Primary outcome measures were Neuropsychiatric Inventory in
      Nursing Home Version total score and its items. Secondary outcome measures were
      cognitive function measured by Mini-Mental State Examination and daily life
      function measured by Functional Independence Measure (FIM). Neurological adverse
      effects were measured by the Drug-Induced Extra-Pyramidal Symptoms Scale. At the
      end of the study, we analyzed 76 patients (92.7%). Mean Neuropsychiatric
      Inventory in Nursing Home Version total score decreased in all 3 drug groups,
      with no significant between-group differences. Mini-Mental State Examination and
      Functional Independence Measure scores did not change significantly. Drug-Induced
      Extra-Pyramidal Symptoms Scale scores did not change in the yokukansan and
      fluvoxamine groups, but increased significantly in the risperidone group.
      Risperidone, yokukansan, and fluvoxamine were equally effective in the treatment
      of BPSD in elderly patients. However, yokukansan or fluvoxamine for BPSD showed a
      more favorable profile in tolerability compared with risperidone. This trial is
      registered at UMIN Clinical Trials Registry (identifier: UMIN000006146). 

PMID- 23948784
TI  - Estimating dopamine D2 receptor occupancy for doses of 8 antipsychotics: a meta
      analysis.
AB  - RATIONALE: Dose equivalents based on dopamine D2 receptor occupancy can be used
      to compare antipsychotics on D2 receptor-mediated (adverse) effects such as
      extrapyramidal symptoms and altered emotional experiences. Previous meta-analyses
      modeling the dose-occupancy relationship hardly addressed potential heterogeneity
      of the imaging data. OBJECTIVES: To model the relationship between dose and D2
      receptor occupancy for a series of frequently prescribed antipsychotics while
      addressing the potential heterogeneity of the imaging data. METHODS: We conducted
      a meta-analysis on published D2 receptor occupancy data (positron emission
      tomography and single-photon emission computed tomography) in patients with
      schizophrenia treated with antipsychotics. A nonlinear mixed effects model
      estimated the median D2 receptor occupancy for a given antipsychotic dose.
      Heterogeneity between studies was investigated by incorporating study as a random
      effect in the model, in addition to patient- and study-specific explanatory
      variables. RESULTS: Included were 51 studies, describing 606 patients (mean +/-
      SD age, 32.2 +/-10.8 years; 25.7% female). The models described the dose
      occupancy relationship with narrow confidence bands around the therapeutic dose
      range. Maximum occupancy (95% confidence interval[CI]) was estimated for
      haloperidol (91.9%; 95% CI, 86.1-97.8), risperidone(92.4%; 95% CI, 81.8-100),
      olanzapine (96.5%; 95% CI,85.8-100), clozapine (61.7%; 95% CI, 49.2-74.2),
      quetiapine (49.1%; 95% CI, 18.7-79.6), aripiprazole (86.9%; 95% CI, 78.2-95.7),
      ziprasidone (82.9%; 95% CI, 44.9-100), and amisulpride (85.0%; 95% CI, 68.5-100).
      Interindividual differences explained most of the variability in occupancy
      values, besides significant heterogeneity between studies. CONCLUSIONS: Dose
      occupancy functions estimated the median level of dopamine D2 receptor occupancy
      for 8 frequently prescribed antipsychotics in patients with schizophrenia. These
      dose equivalents can be used to compare antipsychotic effects in epidemiological
      studies and clinical practice.

PMID- 23948786
TI  - Effects of memantine on clinical ratings, fluorodeoxyglucose positron emission
      tomography measurements, and cerebrospinal fluid assays in patients with moderate
      to severe Alzheimer dementia: a 24-week, randomized, clinical trial.
AB  - Most experts consider that memantine has a symptomatic treatment, but clinical
      trials have not yet provided compelling evidence to support a disease-modifying
      effect. We investigate the effects of memantine on clinical ratings;
      fluorodeoxyglucose positron emission tomography (FDG-PET) measurements, which can
      monitor disease-modifying effect; and cerebrospinal fluid (CSF) assays in
      patients with moderate to severe probable Alzheimer disease (AD) dementia. Twenty
      two patients completed a 24-week, double-blind, placebo-controlled, randomized
      clinical trial of memantine, titrated up to 10 mg twice per day using the Severe
      Impairment Battery, AD Assessment Scale-Cognitive subscale, Mini-Mental State
      Examination, FDG-PET measurements of the regional cerebral metabolic rate for
      glucose (CMRgl), and CSF amyloid beta (Abeta) and tau assays. An automated brain
      mapping algorithm and predefined regions of interest were each used to analyze
      treatment-related regional CMRgl effects. In comparison with the placebo group,
      the memantine treatment group had significantly less cognitive decline on the
      Severe Impairment Battery and significantly less CMRgl declines in regions
      preferentially affected by AD. There were no significant treatment effects on CSF
      Abeta1-42, CSF Abeta1-40, total tau, or phosphor-tau levels or ratios. This
      relatively small and brief randomized clinical trial suggests an association
      between memantine's clinical benefit and its effects on FDG-PET measurements in
      AD-affected brain regions. Larger and longer studies are needed to confirm these
      findings, extend them to earlier clinical and preclinical stages of AD, and help
      determine the extent to which FDG-PET should be qualified for use as a reasonably
      likely surrogate end point in the evaluation of putative AD-modifying treatments.

PMID- 23948785
TI  - A placebo-controlled trial of acetyl-L-carnitine and alpha-lipoic acid in the
      treatment of bipolar depression.
AB  - BACKGROUND: Bipolar disorder may be associated with mitochondrial dysfunction.
      Therefore, agents that enhance mitochondrial functioning may be efficacious in
      bipolar disorder. We performed a randomized placebo-controlled trial of the
      mitochondrial enhancers acetyl-L-carnitine (ALCAR) and alpha-lipoic acid (ALA) in
      patients with bipolar depression, and assessed markers of cerebral energy
      metabolism using phosphorus magnetic resonance spectroscopy. METHODS: We
      administered ALCAR (1000-3000 mg daily) plus ALA (600-1800 mg daily) or placebo
      for 12 weeks to 40 patients with bipolar depression and obtained imaging data at
      baseline, week 1, and week 12 of treatment in 20 patients using phosphorus 3
      dimensional chemical-shift imaging at 4 T. Statistical analysis used random
      effects mixed models. RESULTS: We found no significant difference between
      ALCAR/ALA and placebo on change from baseline in the Montgomery-Asberg Depression
      Rating Scale in both the longitudinal (mean difference [95% confidence interval],
      -1.4 [-6.2 to 3.4], P = 0.58) and last-observation-carried-forward (-3.2 [-7.2 to
      0.9], P = 0.12) analyses. ALCAR/ALA treatment significantly reduced
      phosphocreatine levels in the parieto-occipital cortex at week 12 (P = 0.002).
      Reduction in whole brain total nucleoside triphosphate levels from baseline to
      week 1 was associated with reduction in Montgomery-Asberg Depression Rating Scale
      scores (P = 0.02) in patients treated with ALCAR/ALA. However, this was likely a
      chance finding attributable to multiple statistical comparisons. CONCLUSIONS:
      Treatment with ALCAR and ALA at the dose and duration used in this study does not
      have antidepressant effects in depressed bipolar patients and does not
      significantly enhance mitochondrial functioning in this patient group.

PMID- 23948787
TI  - Open-label treatment with escitalopram in patients with social anxiety disorder
      and fear of blushing.
AB  - Fear of blushing (FB) is a form of social anxiety disorder (SAD) characterized by
      an intense and obsessive threat of blushing in front of other people. No data are
      available on the specific efficacy of antidepressants on FB. This open-label
      pilot study investigated whether the selective serotonin reuptake inhibitor
      escitalopram specifically improves symptoms of FB in SAD patients. Thirty-nine
      patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition criteria for SAD and presenting a significant FB according to the
      Salpetriere Erythrophobia Questionnaire (SEQ) were administered open-label
      escitalopram (10-30 mg/d) for 12 weeks. A systematic assessment, at baseline and
      at week 12, included the SEQ, the Liebowitz Social Anxiety Scale, and the
      Hospital Anxiety and Depression scale. From the 39 patients included, 31 attended
      the week 4 visit, and 28 the week 12 visit. Significant reductions of FB were
      observed after 4 weeks of treatment and were more pronounced at the end of the 12
      week treatment since patients experienced a 60% decrease in their FB symptoms (P
      < 0.001). Nineteen subjects (67.8%) reported a 50% decrease or more of their SEQ
      score, and 14 (50%) met criteria for remission of FB (SEQ score <7). The effect
      sizes of changes on SEQ, Liebowitz Social Anxiety Scale, and Hospital Anxiety and
      Depression scale scores were high, with eta2 ranging between 0.53 and 0.86.
      Results of this open-label study suggest that escitalopram can be a useful
      treatment for FB associated with SAD, even if large controlled trials are now
      needed to further evaluate this result.

PMID- 23948788
TI  - Rivastigmine as an effective add-on to standard treatment of veterans with
      chronic posttraumatic stress disorder: a case series.
AB  - BACKGROUND: After 23 years of the end of the Iran-Iraq war, the country is left
      with many patients with chronic posttraumatic stress disorder (PTSD) who need
      close psychiatric services and are in need for recurrent hospitalization. So far,
      there are no reports of the rivastigmine use in PTSD patients. We report dramatic
      reduction of symptoms in 3 veterans with chronic PTSD, after rivastigmine
      augmentation. CASE PRESENTATION: This report describes the efficacy of
      rivastigmine as an add-on to standard treatment of 3 Iranian male veterans with
      chronic PTSD (aged 52, 46, and 45 years) with severe active symptoms in all 3
      dimensions of the disorder. Although they had gone through many approved drug
      treatments (selective serotonin reuptake inhibitors, tricyclic antidepressants,
      mood stabilizers, antipsychotics, benzodiazepines, beta-blockers, and so on),
      from the beginning of the disorder, their recovery remained poor (PTSD Checklist
      Military Version [PCL-M] scores were 67, 71, and 73 before rivastigmine add-on).
      Rivastigmine was added to the ongoing therapeutic regimens of the patients for 6
      months.Evaluating their condition with PCL-M after 1 and 6 months of treatment
      showed a significant improvement in patients with PTSD (PCL-M scores were 37, 40,
      and 47 and dropped to 30, 27, and 31, respectively). Hyperarousal symptoms of
      PTSD in patients are noted to be the most improved. The rivastigmine add-on
      experience did not report any adverse effects. CONCLUSIONS: The present study
      showed that rivastigmine is an effective and safe add-on to treatment of patients
      with chronic PTSD. This effect could be due to improved cognitive status or
      cholinergic-adrenergic balance adjustment in patients.

PMID- 23948789
TI  - Pseudo-inflammatory bowel disease related to quetiapine fumarate: a case report.

PMID- 23948790
TI  - Successful treatment of a patient with long-standing history of catatonic
      schizophrenia with pregabalin.

PMID- 23948791
TI  - Dramatic improvement of fibromyalgia symptoms after treatment with topiramate for
      coexisting migraine.

PMID- 23948792
TI  - Relationship between mean platelet volume and major depression.

PMID- 23948794
TI  - A 9-year-old boy with atypical retroauricular pain: a case report.
AB  - Idiopathic causes of retroauricular pain are rarely seen in clinical practice. We
      present a 9-year-old child who suffered from atypical retroauricular pain
      resistant to conventional treatment. After excluding any other cause of
      retroauricular pain, a nerve block was performed with a 0.3 ml lidocaine 1%
      injection into the trigger point. We believe that this case report is important
      because in the literature there are no similar cases described in children.

PMID- 23948795
TI  - A therapeutic dilemma: quality versus quantity.

PMID- 23948796
TI  - Palliative epilepsy surgery in Aicardi syndrome: a case series and review of
      literature.
AB  - PURPOSE: Aicardi syndrome (AS) is a severe neurodevelopmental disorder
      characterized by the triad of seizures, agenesis of corpus callosum, and
      chorioretinal lacunae. Seizures in AS are typically frequent, of various types,
      and refractory to medical therapy. Optimal treatment of seizures in AS remains
      undetermined. METHODS: We report a series of four patients with Aicardi syndrome
      who underwent surgical management of their epilepsy including two with corpus
      callosotomy (CC) of a partial corpus callosum and three with vagus nerve
      stimulator implantation. RESULTS: Seizure outcome was variable and ranged from
      near complete resolution of seizures to worsening of seizure profile. The most
      favorable seizure outcome was seen in a patient with partial agenesis of the
      corpus callosum treated with CC. CONCLUSIONS: Seizure outcome following CC or
      vagus nerve stimulation in patients with Aicardi syndrome is variable. Although
      palliative epilepsy surgery may result in improvement in the seizure profile in
      some patients, studies on larger patient cohorts are needed to identify the
      precise role that surgery may play in the multidisciplinary approach to
      controlling seizures in Aicardi syndrome.

PMID- 23948798
TI  - Quantitative PCR analysis used to characterize physiological changes in brain
      tissue of senescent sockeye salmon.
AB  - Senescence varies considerably among fishes, and understanding the evolutionary
      basis for this diversity has become an important area of study. For rapidly
      senescing species such as Pacific salmon, senescence is a complex process as
      these fish are initiating anorexia while migrating to natal spawning grounds, and
      die within days of reproduction. To better understand senescence in Pacific
      salmon we examined expression patterns for a suite of genes in brain tissue of
      pre-senescent and senescent sockeye salmon. Interestingly, a significant increase
      in expression of genes involved in telomere repair and immune activity was
      observed in senescent salmon. These data provide insight into physiological
      changes in salmon undergoing senescence and the factors contributing to variation
      in observed senescence rates among individuals and populations. 

PMID- 23948797
TI  - Cardiotoxicity and cancer therapy: treatment-related cardiac morbidity in
      patients presenting with symptoms suggestive of heart or lung disease.
AB  - OBJECTIVES: Cardiac injury is one of the complications of cancer treatment. This
      study aimed to investigate the relationships between the types of radiotherapy of
      the chest (RT), chemotherapy (CT), cancer surgery (CS) and endocrine therapy
      (ET), and the presence of heart disease, and their associations with the serum
      level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). METHODS: A
      consecutive series of 374 patients with cancer who were referred because of
      symptoms suggestive of heart or lung disease prospectively underwent a diagnostic
      workup. RESULTS: The prevalence of heart disease was 36.9%. RT administered
      before 1995 (n = 19) was associated with both increased odds of heart disease
      [adjusted odds ratio 10.3, 95% confidence interval 3.1-34.0] and higher ln
      transformed NT-proBNP values (p < 0.01) compared to the control group (no RT or
      RT for right-sided breast cancer from 1995 onwards; n = 311). Anthracycline
      treated patients (n = 54) had higher adjusted values for ln(NT-proBNP) compared
      to the control group (no CT; n = 243; p < 0.01) but no increased odds of heart
      disease. CONCLUSIONS: While pre-1995 RT and anthracycline-containing CT were
      associated with cardiac effects, there was no evidence that RT using modern
      cardioprotective techniques, CT in the absence of anthracyclines, CS or ET had
      detrimental effects on the heart.

PMID- 23948799
TI  - Lipidomics in longevity and healthy aging.
AB  - The role of classical lipids in aging diseases and human longevity has been
      widely acknowledged. Triglyceride and cholesterol concentrations are clinically
      assessed to infer the risk of cardiovascular disease while larger lipoprotein
      particle size and low triglyceride levels have been identified as markers of
      human longevity. The rise of lipidomics as a branch of metabolomics has provided
      an additional layer of accuracy to pinpoint specific lipids and its association
      with aging diseases and longevity. The molecular composition and concentration of
      lipid species determine their cellular localization, metabolism, and
      consequently, their impact in disease and health. For example, low density
      lipoproteins are the main carriers of sphingomyelins and ceramides, while high
      density lipoproteins are mostly loaded with ether phosphocholines, partly
      explaining their opposing roles in atherogenesis. Moreover, the identification of
      specific lipid species in aging diseases and longevity would aid to clarify how
      these lipids alter health and influence longevity. For instance, ether
      phosphocholines PC (O-34:1) and PC (O-34:3) have been positively associated with
      longevity and negatively with diabetes, and hypertension, but other species of
      phosphocholines show no effect or an opposite association with these traits
      confirming the relevance of the identification of molecular lipid species to
      tackle our understanding of healthy aging and disease. Up-to-date, a minor
      fraction of the human plasma lipidome has been associated to healthy aging and
      longevity, further research would pinpoint toward specific lipidomic profiles as
      potential markers of healthy aging and metabolic diseases. 

PMID- 23948800
TI  - The RESOLVE concept: approaching pathophysiology of fibroproliferative disease in
      aged individuals.
AB  - After reaching adulthood, orderly repair is probably one of the most important
      mechanisms throughout lifetime. Regular wound healing after an injury consists of
      a well-ordered sequence of overlapping phases of repair and essentially repeats
      the complex process of organ development. Organ failure in the ageing organism
      frequently represents the lost capacity to achieve an orderly reactivation of
      organ development, yet in varying and complex pathologic settings. One of the
      most aggressive manifestations of age-dependent and dysbalanced wound healing is
      a disease called idiopathic pulmonary fibrosis. Essentially, the disease replaces
      functional lung tissue with spreading scar tissue over a period of just 5 years.
      By a systematic comparison of wound healing conditions, the large-scale
      collaborative FP7-EU project RESOLVE has addressed these difficulties in a
      successful way. Background and outlining of the project are discussed. 

PMID- 23948802
TI  - Long-term survival following gross total resection of pediatric supratentorial
      ependymomas without adjuvant therapy.
AB  - Pediatric supratentorial ependymoma is very rare. In pediatric patients with
      supratentorial ependymoma, surgery alone may be an acceptable treatment when
      postoperative imaging confirms a gross total resection. Surgical resection is the
      standard and the most important treatment for ependymoma. The role of radiation
      therapy and/or chemotherapy following a gross total resection of supratentorial
      ependymoma has been uncertain. We report 2 cases of pediatric supratentorial
      ependymomas treated by gross total resection without postoperative adjuvant
      therapy. The first patient was a 7-year-old girl who presented with motor
      weakness and a hemiconvulsion of the right leg. Magnetic resonance imaging (MRI)
      revealed a large heterogeneously enhanced tumor in the left frontal lobe. The
      second patient was an 8-year-old girl who presented with headache. MRI revealed a
      huge heterogeneously enhanced tumor in the left frontal lobe. Gross total
      resection was achieved in both patients. Postoperative radiotherapy and
      chemotherapy were avoided following gross total resection. Histologically, the
      lesions demonstrated grade II ependymoma and anaplastic ependymoma, respectively.
      After follow-up of 120 months, neither patient had recurrence or dissemination.
      These results suggest that patients with pediatric supratentorial ependymoma
      treated by gross total resection alone have a favorable outcome, and
      postoperative radiotherapy and chemotherapy may be avoided.

PMID- 23948804
TI  - Breast metastases from an adrenocorticotropic hormone secreting thymic neuro
      endocrine tumor.
AB  - Metastases to the breast from non-mammary sites are rare and pose a diagnostic
      and therapeutic challenge. They can be mistaken for primary breast malignancy,
      which is much more common. In this case report we describe the clinical,
      radiological and pathological features of a patient who developed breast
      metastases from an adrenocorticotropic hormone (ACTH) secreting thymic neuro
      endocrine carcinoma. Patient was initially felt to have a primary breast
      malignancy, however, after further ancillary testing a diagnosis of metastatic
      thymic neuro-endocrine tumor was made. 

PMID- 23948801
TI  - Whole transcriptome sequencing reveals genes involved in plastid/chloroplast
      division and development are regulated by the HP1/DDB1 at an early stage of
      tomato fruit development.
AB  - The phenotype of tomato high pigment-1 (hp1) mutant is characterized by
      overproduction of pigments including chlorophyll and carotenoids during fruit
      development and ripening. Although the increased plastid compartment size has
      been thought to largely attribute to the enhanced pigmentation, the molecular
      aspects of how the HP1/DDB1 gene manipulates plastid biogenesis and development
      are largely unknown. In the present study, we compared transcriptome profiles of
      immature fruit pericarp tissue between tomato cv. Ailsa Craig (WT) and its
      isogenic hp1 mutant. Over 20 million sequence reads, representing > 1.6 Gb
      sequence data per sample, were generated and assembled into 21,972 and 22,167
      gene models in WT and hp1, respectively, accounting for over 60 % official gene
      models in both samples. Subsequent analyses revealed that 8,322 and 7,989
      alternative splicing events, 8833 or 8510 extended 5'-UTRs, 8,263 or 8,939
      extended 3'-UTRs, and 1,136 and 1,133 novel transcripts, exist in WT and hp1,
      respectively. Significant differences in expression level of 880 genes were
      detected between the WT and hp1, many of which are involved in signaling
      transduction, transcription regulation and biotic and abiotic stresses response.
      Distinctly, RNA-seq datasets, quantitative RT-PCR analyses demonstrate that, in
      hp1 mutant pericarp tissue at early developmental stage, an apparent expression
      alteration was found in several regulators directly involved in plastid division
      and development. These results provide a useful reference for a more accurate and
      more detailed characterization of the molecular process in the development and
      pigmentation of tomato fruits.

PMID- 23948805
TI  - Short-lived success: assessment of an intervention to improve pregnancy weight
      gain in Colorado.
AB  - Inadequate weight gain in pregnancy is a major contributor to low birth weight in
      Colorado, where the low birth weight rate is among the highest in the nation. In
      2004, the Colorado Department of Public Health and Environment implemented a
      population-based intervention in 9 counties, including provider training and a
      public media campaign, to encourage pregnant women to gain an adequate amount of
      weight in pregnancy as defined by the 1990 Institute of Medicine guidelines.
      Pregnancy Risk Assessment Monitoring System survey data were used to track weight
      gain in pregnancy in 1997 through 2004 (baseline), 2005 (post-intervention), and
      2006 and 2007 (after the intervention had concluded). During the period
      immediately after the implementation of the intervention, the percentage of women
      delivering in the 9 study counties who gained an inadequate amount of weight
      during pregnancy dropped from 18.4 at baseline to 12.8 in 2005. However, this
      progress was reversed in 2006, when the percentage of women with inadequate
      weight gain rose to 19.7. Training providers to educate women about the
      importance of adequate weight gain in pregnancy, in conjunction with a social
      marketing campaign, appears to be a promising approach to addressing a major
      contributor to low birth weight. However, a time-limited intervention is likely
      to have temporary results. 

PMID- 23948806
TI  - Antenatal care attendance, a surrogate for pregnancy outcome? The case of Kumasi,
      Ghana.
AB  - Antenatal care (ANC) has been shown to influence infant and maternal outcomes.
      WHO recommends 4 ANC visits for uncomplicated pregnancies. However, pregnant
      women in Ghana are required to attend 8-13 antenatal visits. We investigated the
      association of ANC attendance with adverse pregnancy outcomes (defined as low
      infant birth weight, stillbirth, preterm delivery or small for gestational age).
      A quantitative cross-sectional study was conducted on 629 women, age 19-48 years
      who presented for delivery at two selected public hospitals and 16 traditional
      birth attendants from July to November 2011. Socio-demographic and antenatal
      information were collected using a structured questionnaire. ANC attendance,
      medical and obstetric/gynecological history were abstracted from maternal
      antenatal records. Data were analyzed using Chi square and logistic regression.
      Twenty-two percent of the women experienced an adverse outcome. Eleven percent of
      the women attended <4 ANC visits. In an unadjusted model, these women had an
      increased likelihood of experiencing an adverse outcome (OR 2.27; 95% CI 1.30
      3.94; p = 0.0038). High parity (>5 children) was also associated with adverse
      birth outcomes. Women screened for syphilis or use of insecticide-treated bed
      nets had a 40 and 36% (p = 0.0447 and p = 0.0293) reduced likelihood of
      experiencing an adverse pregnancy outcome respectively. After adjusting for
      confounders, attending <4 antenatal visits was associated with adverse pregnancy
      outcome compared with >=4 ANC visits (Adjusted OR 2.55; 95% CI 1.16-5.63; p =
      0.0202). Attending <4 antenatal visits and high parity were associated with
      adverse pregnancy outcomes for uncomplicated pregnancies.

PMID- 23948808
TI  - Photocatalytic hydrogen production of Co(OH)2 nanoparticle-coated alpha-Fe2O3
      nanorings.
AB  - The production of hydrogen from water using only a catalyst and solar energy is
      one of the most challenging and promising outlets for the generation of clean and
      renewable energy. Semiconductor photocatalysts for solar hydrogen production by
      water photolysis must employ stable, non-toxic, abundant and inexpensive visible
      light absorbers capable of harvesting light photons with adequate potential to
      reduce water. Here, we show that alpha-Fe2O3 can meet these requirements by means
      of using hydrothermally prepared nanorings. These iron oxide nanoring
      photocatalysts proved capable of producing hydrogen efficiently without
      application of an external bias. In addition, Co(OH)2 nanoparticles were shown to
      be efficient co-catalysts on the nanoring surface by improving the efficiency of
      hydrogen generation. Both nanoparticle-coated and uncoated nanorings displayed
      superior photocatalytic activity for hydrogen evolution when compared with TiO2
      nanoparticles, showing themselves to be promising materials for water-splitting
      using only solar light.

PMID- 23948809
TI  - Neural correlate of resting-state functional connectivity under alpha2 adrenergic
      receptor agonist, medetomidine.
AB  - Correlative fluctuations in functional MRI (fMRI) signals across the brain at
      rest have been taken as a measure of functional connectivity, but the neural
      basis of this resting-state MRI (rsMRI) signal is not clear. Previously, we found
      that the alpha2 adrenergic agonist, medetomidine, suppressed the rsMRI
      correlation dose-dependently but not the stimulus evoked activation. To
      understand the underlying electrophysiology and neurovascular coupling, which
      might be altered due to the vasoconstrictive nature of medetomidine,
      somatosensory evoked potential (SEP) and resting electroencephalography (EEG)
      were measured and correlated with corresponding BOLD signals in rat brains under
      three dosages of medetomidine. The SEP elicited by electrical stimulation to both
      forepaws was unchanged regardless of medetomidine dosage, which was consistent
      with the BOLD activation. Identical relationship between the SEP and BOLD signal
      under different medetomidine dosages indicates that the neurovascular coupling
      was not affected. Under resting state, EEG power was the same but a depression of
      inter-hemispheric EEG coherence in the gamma band was observed at higher
      medetomidine dosage. Different from medetomidine, both resting EEG power and BOLD
      power and coherence were significantly suppressed with increased isoflurane
      level. Such reduction was likely due to suppressed neural activity as shown by
      diminished SEP and BOLD activation under isoflurane, suggesting different
      mechanisms of losing synchrony at resting-state. Even though, similarity between
      electrophysiology and BOLD under stimulation and resting-state implicates a tight
      neurovascular coupling in both medetomidine and isoflurane. Our results confirm
      that medetomidine does not suppress neural activity but dissociates connectivity
      in the somatosensory cortex. The differential effect of medetomidine and its
      receptor specific action supports the neuronal origin of functional connectivity
      and implicates the mechanism of its sedative effect. 

PMID- 23948807
TI  - Risk of fracture in patients with muscular dystrophies.
AB  - The aim of the study was to determine fracture risk in incident muscular
      dystrophy (MD) patients. Patients with MD are at a 1.4-fold increased risk of
      fracture as compared with population-based control patients. Risk further
      increased among elderly and female patients and among patients exposed to oral
      glucocorticoids. INTRODUCTION: Muscular dystrophies (MDs) are inherited diseases
      causing muscle weakness and thereby increase the risk of falling and detrimental
      effects on bone. Both are recognised risk factors for fracture. Therefore, the
      aim of this study was to determine the hazard ratio of fracture in patients with
      MD. METHODS: We conducted a retrospective cohort study using the UK General
      Practice Research Database (1987-2012). Each patient with MD was matched by year
      of birth, sex and practice to up to six patients without a history of MD. Outcome
      measure was all fractures. RESULTS: As compared with control patients, risk of
      any fracture was statistically significantly increased in MD patients (adjusted
      hazard ratio [AHR], 1.40; 95 % confidence interval [CI], 1.14-1.71). An increased
      risk of fracture was observed among MD patients with female gender (AHR, 1.78; 95
      % CI, 1.33-2.40) and an increasing age as compared with control patients.
      Stratification to Duchenne MD showed no association with fracture, whereas risk
      of fracture was increased twofold among patients with myotonic dystrophy (AHR,
      2.34; 95 % CI, 1.56-3.51). MD patients had an almost tripled risk of fracture
      when they used oral glucocorticoids in the previous 6 months as compared to non
      users with MD. CONCLUSION: Patients with MD are at a 1.4-fold increased risk of
      fracture as compared with population-based control patients. Especially in older
      age groups and female gender, the fracture risk of MD versus non-MD patients is
      increased, whereas exposure to glucocorticoids further increased fracture risk
      among MD patients.

PMID- 23948811
TI  - Current challenges to academic health centers.

PMID- 23948812
TI  - Association of Hirschsprung's disease and anorectal malformation: a systematic
      review.
AB  - BACKGROUND: The association of Hirschsprung's disease (HD) and anorectal
      malformation (ARM) is rare. The exact incidence of this association is not known
      but HD coexisting with ARM has been reported in 2.3 to 3.4% of ARM cases. Most of
      the reported cases in the literature have been single case reports. The aim of
      this systematic review was to determine the incidence of HD associated with ARM
      and its relationship to other syndromes. METHODS: A systematic review of the
      literature was performed for the keywords "association of Hirschsprung's disease
      and anorectal malformation", "aganglionosis and anorectal malformation" as well
      as "congenital megacolon and anorectal malformation". Resulting publications were
      reviewed for epidemiology, operative treatment and morbidity. Reference lists
      were screened for additional cases. RESULTS: A total of 38 articles reported 90
      cases of HD coexisting with ARM from 1952 to 2013. Twenty eight articles reported
      40 single case reports of this association. Ten articles reported 50 cases of HD
      in case series of 2,465 ARM patients, resulting in an incidence of 2% of this
      association. Gender was reported in 63 cases, with 30 males (48%) and 33 females
      (52%). Associated syndromes were reported in 23 patients: Currarino syndrome in
      11, Down syndrome in 8, Cat eye syndrome in 3 and Pallister-Hall syndrome in one
      case. Extent of aganglionosis was reported in 49 cases and included classical
      rectosigmoid disease in 36, long segment aganglionosis in 5, total colonic
      aganglionosis in 7 and total intestinal aganglionosis in one patient. In 35% of
      the patients stoma was created in the aganglionotic region and failed to work.
      There was a median delay of 8 months for the diagnosis of HD from initial
      diagnosis of ARM. Various surgical techniques were employed for the pull-through
      operation for HD. CONCLUSION: The review confirms that the recognition of HD is
      often delayed because of the initial diagnosis of ARM and the fact that the
      dysfunctional colostomy is usually proximal to the affected aganglionotic bowel.
      There is a high incidence of associated syndromes when HD coexists with ARM.

PMID- 23948813
TI  - Long-term follow-up of paediatric anorectal anomalies and the role and efficacy
      of parent support groups for such conditions.
AB  - BACKGROUND/PURPOSE: There are a multitude of parent support groups for most life
      situations and medical conditions. The aim of this study was to discover defining
      characteristics and to evaluate the structure and effectiveness of parent support
      groups in paediatric anorectal anomalies. METHODS: Over 200 non-profit
      organisations and parent support groups were sent questionnaires to determine
      their effectiveness. Many of these were excluded as they were deemed not relevant
      to the final study. A final 20 groups were included for review, questions were
      based around origins, activities, education and evaluation, organisational
      structure and their affiliations with the health care team. RESULTS: Most groups
      had similar origins, usually an educated parent who had a child born with the
      condition and a zest for further knowledge and understanding and a desire to
      share this with others in a similar situation. Only 20% received government
      funding; few had paid staff and half had good relations with the local medical
      and paramedical fraternity. The majority had a team of long-term enthusiastic
      volunteers who remained with the group to support others long after their own
      child was no longer a concern. CONCLUSIONS: Some support groups offer a valuable
      service to families alongside the medical and paramedical fraternity. These
      groups provide families with the day-to-day lived experiences through social
      media, networking and meetings. Some provide more formal educational conferences
      designed to bring families, the medical and paramedical fraternity together to
      learn valuable lessons from each other.

PMID- 23948814
TI  - Long-term results of biliary atresia in the era of liver transplantation.
AB  - PURPOSE: The purpose of this study was to analyze the survival of patients with
      biliary atresia (BA) after Kasai operation and liver transplantation (LT) and to
      analyze the factors affecting survival. METHODS: Seventy-two patients diagnosed
      with BA were operated on between April 1995 and December 2009 and retrospectively
      analyzed. RESULTS: Out of the 72 patients, 59 received Kasai operation and 13
      received LT without prior Kasai operation. Twenty-seven patients received LT
      after Kasai operation. Survival with native liver was 39 % at 10 years. With the
      application of LT, overall 10-year survival for patients with BA was 94.9 %.
      Among patients alive with native livers after Kasai operation, 14 patients (58.3
      %) have at least one complication associated with biliary cirrhosis and portal
      hypertension. Age at which Kasai operation was performed (60 days) and
      postoperative normalization of bilirubin were independent risk factors for
      survival with the native liver, according to multivariate analysis (HR 2.90, p =
      0.033 and HR 9.89, p = 0.002). CONCLUSIONS: Survival of BA patients has greatly
      increased in the era of LT. However, many patients surviving with native livers
      after Kasai operation continue to have signs of biliary cirrhosis and abnormal
      liver function.

PMID- 23948815
TI  - Skip segment Hirschsprung's disease: a case report and novel management
      technique.
AB  - Skip segment Hirschsprung's disease is a condition where an area of normally
      ganglionated intestine is interspersed proximally and distally by aganglionic
      segments. The occurrence of skip segment has no clear embryological explanation,
      contrary to the present concept of failure of cranio-caudal migration of neural
      crest-derived cells in Hirschsprung's disease. Only 25 case reports have been
      published in literature so far and this is possibly the first to be reported from
      Asia. We report one such case with novel surgical management. 

PMID- 23948816
TI  - A mutation in the gene for polynucleotide kinase of bacteriophage T4 K10 affects
      mRNA processing.
AB  - The bacteriophage T4 insertion-substitution (I/S) vector system has become one of
      the most important tools for the introduction of site-directed mutations into the
      T4 genome. In this study, we show that the I/S phage T4 K10 carries two point
      mutations within the gene for polynucleotide kinase pseT, resulting in amino acid
      substitutions G14D and R229H. The G14D mutation impairs 5'-kinase activity in
      vivo as well as in vitro and leads to diminished processing at secondary sites of
      several RegB-cleaved transcripts. 

PMID- 23948818
TI  - Post-partum low-back pain of an uncommon origin: a case report.
AB  - Low-back pain is a common complaint during pregnancy and the post-partum period,
      and it may be due to a variety of conditions. Among these, a frequently
      overlooked cause is a sacral fracture. We report the case of a 37 year old woman,
      suffering from post-partum low-back pain which had not responded to treatment.
      Though rare, a sacral stress fracture must be considered in cases of prolonged
      low-back or sacral pain in pregnant or post-partum women. Plain radiographs are
      frequently inconclusive and MRI is the imaging technique of choice. Capacitive
      coupling electric fields (CCEF) seemed to be effective in treating pain and in
      reducing the patient's recovery time. 

PMID- 23948819
TI  - The effect of non-weight bearing group-exercising on females with non-specific
      chronic low back pain: a randomized single blind controlled pilot study.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of active non
      weight-bearing (NWB) group exercising on women with non specific chronic low back
      pain (NSCLBP). METHODS: Forty females with NSCLBP were assigned in a randomized
      control longitudinal single blinded pilot study. 20 of them were assigned to a
      NWB bi-weekly group exercise class and 20 females were included in the control
      group. The exercises involved the entire lumbo-pelvic spine aimed at improving
      lumbar mobility/flexibility and stability. Pain intensity (VAS), back specific
      disability (Rolland Morris questionnaire-RMQ), and lumbar flexion and extension
      ranges of motion measurements were taken prior to intervention (t(0)),
      immediately following 4 weeks of intervention (t(1)) and 8 weeks later (t(fu)).
      Reliability trials were conducted on 10 females. Non-parametric tests were used
      for statistical significance (p < 0.05). RESULTS: The following significant
      changes in outcome measures were indicated at t(1) compared with t(0) and control
      group (p < 0.001): an increase in lumbar flexion and extension (mean difference =
      9.26? (+54%) for flexion and 5.95? for extension(+98%)); reduction in VAS score
      (mean difference = 2.32 (+58%)) and RMQ score (mean difference = 4.9 (-34%)). All
      changes remained significant at t(fu). At t(0), lumbar flexion was correlated
      with extension (r = 0.547) and VAS (r = -0.581),whereas the RMQ score correlated
      with VAS score (r = 0.599) and negatively with lumbar extension (r = -0.665). At
      t(1),lumbar flexion correlated with extension (r = 0.664) and negatively with RMQ
      score (r = -0.54). At t(fu), changes in VAS score were negatively correlated with
      changes in lumbar flexion (r = -0.522), while changes in lumbar flexion
      correlated with extension (r = 0.58). CONCLUSIONS: A functional program of NWB
      group exercising improves functional, painful status, lumbar flexion and
      extension ranges of motion in women suffering from NSCLBP.

PMID- 23948820
TI  - Association with isokinetic ankle strength measurements and normal clinical
      muscle testing in sciatica patients.
AB  - BACKGROUND: Sensitive muscle strength tests are needed to measure muscle strength
      in the diagnosis and management of sciatica patients. OBJECTIVE: The aim of this
      study was to assess the isokinetic muscle strength in sciatica patients' and
      control subjects' ankles that exhibited normal ankle muscle strength when
      measured clinically. METHODS: Forty-six patients with L5 and/or S1 nerve
      compression, and whose age, sex, weight, and height matched 36 healthy
      volunteers, were recruited to the study. Heel-walking, toe-walking, and manual
      muscle testing were used to perform ankle dorsiflexion and plantar flexion
      strengths in clinical examination. Patients with normal ankle dorsiflexion and
      plantar flexion strengths assessed by manual muscle testing and heel-and toe
      walking tests were included in the study. Bilateral isokinetic
      (concentric/concentric) ankle plantar-flexion-dorsiflexion measurements of the
      patients and controls were performed within the protocol of 30 degrees /sec (5
      repetitions). Peak torque and peak torque/body weight were obtained for each
      ankle motion of the involved limb at 30 degrees /s speed. RESULTS: L5 and/or S1
      nerve compression was evident in 46 patients (76 injured limbs). Mean disease
      duration was two years. The plantar flexion muscle strength of the patients was
      found to be lower than that of the controls (p=0.036). The dorsiflexion muscle
      strength of the patients was found to be the same as that of the controls
      (p=0.211). CONCLUSIONS: Isokinetic testing is superior to clinical muscle testing
      when evaluating ankle plantar flexion torque in sciatica patients. Therefore,
      isokinetic muscle testing may be helpful when deciding whether to place a patient
      into a focused rehabilitation program.

PMID- 23948821
TI  - Predictors of objectively measured walking capacity in people with degenerative
      lumbar spinal stenosis.
AB  - BACKGROUND: Identifying factors associated with walking capacity in people with
      lumbar spinal stenosis (LSS) may provide a better understanding of neurogenic
      claudication and inform future rehabilitation research. OBJECTIVE: To examine
      factors associated with objectively measured walking capacity in a sample of
      people with LSS and self-reported walking limitations. METHODS: Participants
      included 49 individuals (65.8 years +/- 10) who were at least 45 years of age
      with clinically diagnosed lumbar spinal stenosis (LSS) confirmed on MRI or CT
      imaging. All participants completed a Self-Paced Walking Test with visual analog
      pain scales and body diagrams before and immediately after walking.
      Questionnaires included the Physical Function and Symptom Severity Scales of the
      Swiss Spinal Stenosis Questionnaire, the Oswestry Disability Index (ODI) and the
      Health Utilities Index. Univariate linear relationships were examined, followed
      by development of a multivariate linear regression model with walking distance
      (m) as the dependent variable. A post-hoc analysis was also conducted including
      post-test symptom variables. RESULTS: Variables retained from univariate analyses
      included years of leg pain, pre-test leg pain severity, the ODI, balance
      problems, and quality of life. When these variables were considered for a final
      model, only the ODI and balance problems were retained (R2=0.33). Other than
      balance, none of the pre-test symptom variables entered into the final model.
      Post-hoc analysis including post-test symptom variables found the presence and
      severity of post-test leg pain to be most highly associated with walking
      distance. In an explanatory model considering the ODI, balance and these two post
      walking factors, only presence of post-test leg pain added to the model
      (R2=0.42). CONCLUSIONS: Factors found to be most highly associated with walking
      capacity in LSS were self-reported, pain-related function (ODI), balance
      problems, and presence of leg pain immediately following walking.

PMID- 23948822
TI  - Low back pain in patients with rheumatoid arthritis: clinical characteristics and
      impact of low back pain on functional ability and health related quality of life.
AB  - OBJECTIVES: The aim of this study was to assess the point prevalence of low back
      pain (LBP) in patients with rheumatoid arthritis (RA); and to compare
      radiological and clinical aspects, as well as impact of LBP on health related
      quality of life (QoL), depression and disability in control patients with
      mechanical LBP (mLBP). METHODS: Patients with RA and patients with mLBP of at
      least 3 months duration were consecutively recruited. All patients were examined
      and underwent lumbar X-ray and magnetic resonance (MR) imaging. Disc intensity,
      annulus fibrosis rupture, herniated nucleus pulposus (bulging, protrusion,
      extrusion or sequestration), stenosis, Schmorl nodes, hemangiomas, Tarlov cysts,
      Type I or II degeneration, ligamentum flavum hypertrophy and loss of lordosis
      were assessed on MR. Assessments included QoL and disability scales like RAQoL,
      Short Form-36, Health Assessment Questionnaire (HAQ) and Oswestry Disability
      Index (ODI) and depression and anxiety scales as well. RESULTS: Chronic LBP
      coexisted in 64.5% of patients with RA. Patients with LBP had higher scores on
      VAS-LBP compared to patients with RA+LBP. Additionally, patients with RA+LBP had
      the poorest scores on quality of life, functional disability and depression.
      Patients with mLBP had more frequent clinical manifestations and neurologic
      deficits. Patients with RA+LBP had more frequent Schmorl nodes compared to
      patients with mLBP. CONCLUSION: The association of RA with LBP leads to a
      significant decrease in the functional capacity and QoL as well as increase in
      depression risk. Appropriate diagnostic procedures and treatments should be
      administered to avoid further deterioration in functional disability and QoL.

PMID- 23948823
TI  - The effect of myofascial neck pain on postural control: visual deprivation.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the standing
      balance (with open and closed eyes) on rigid surface in women with myofascial
      neck pain syndromes. MATERIAL AND METHOD: This study was carried out in single
      and double limbs stances, open versus closed eyes, and the results were compared
      with control group. Forty subjects (20 in each group) were tested on a force
      platform, during 30 seconds. The mean velocity (cm/s), surface area (cm2), antero
      posterior and medio-lateral displacements (cm) of center of foot pressure (COP)
      were determined. RESULTS: There were significant differences between two groups
      regarding the mean velocity and area of COP displacements. In addition,
      significant differences were observed in respect to eye and limb conditions (open
      versus closed; single versus double limbs stances; respectively) on mean
      velocity, area, antero-posterior (AP) and medio-lateral (ML) displacements of
      COP. CONCLUSION: Our results showed that myofascial neck pain syndrome might be
      one of the disturbing factors on standing balance.

PMID- 23948824
TI  - The value of physical examination in the diagnosis of hip osteoarthritis.
AB  - OBJECTIVE: To compare the sensitivity of physical examination (internal rotation
      of the hip) with radiographs (using the Kellgren-Lawrence grading scale) in the
      diagnosis of clinically significant hip osteoarthritis. DESIGN: Case Series,
      Retrospective chart review of hip pain patients that underwent fluoroscopically
      guided hip steroid and anesthetic injections. PARTICIPANTS: 10 patients with hip
      pain patients seen at an academic outpatient center over a 2 year period were
      analyzed. INTERVENTIONS: Fluoroscopically guided hip steroid and anesthetic
      injection. MAIN OUTCOME MEASURE: Pain relief and change in VAS pain score after
      intra-articular hip steroid and lidocaine injection was the main outcome measure.
      RESULTS: Based on Fisher's exact test, there was no association between severity
      of radiographic hip arthritis and pain relief with intra-articular
      anesthetic/steroid injection (p=0.45). Physical examination (provocative hip
      internal rotation) however was associated with a significant decrease in VAS pain
      score after intra-articular lidocaine and corticosteroid hip injection (p=0.022).
      CONCLUSION: Simple hip radiographs alone are not sufficient to diagnose
      clinically significant hip osteoarthritis. Physical examination (hip internal
      rotation) was found to be more accurate than simple radiographs in the diagnosis
      of clinically significant hip osteoarthritis. Radiographs seem to best utilized
      when they are an extension of the physical examination and patient history.

PMID- 23948825
TI  - Effects of proprioceptive disruption on lumbar spine repositioning error in a
      trunk forward bending task.
AB  - BACKGROUND: Various inputs of proprioception have been identified and shown to
      influence low back proprioception sense. OBJECTIVE: To investigate the effect of
      disrupting proprioception on lumbar spine repositioning error during forward
      bending. METHOD: Healthy-subjects (n=28) and patients with non-specific chronic
      low-back pain (n=10) aged between 20-50 years. Subjects performed 5 repetitions
      of a lumbar repositioning task targeting 30 degrees  of trunk-forward-bending
      from a seated-position with different proprioceptive disturbances administered to
      the low back. Video analysis of skin reflective markers measured lumbar spine
      range-of-motion. A control-task was performed without any proprioceptive
      disturbance, while the remaining 4 tasks were electro-stimulation, vibration,
      taping and sitting on an unstable surface. RESULTS: The healthy group showed
      significantly altered repositioning error when compared with the control task
      (p=0.004): control-task vs. taping-task, vibration-task and unstable-sitting. In
      the NS-CLBP group, one motor-task showed significant difference in control-task
      vs. taping-task (p=0.004). Comparison between the NS-CLBP and matched-healthy
      groups revealed that the NS-CLBP subjects had larger repositioning-error
      (p=0.009) for control, taping and vibration tasks. CONCLUSIONS: Proprioceptive
      disturbances had the most significant effect in increasing repositioning-error
      among healthy subjects. The between-groups analysis confirmed evidence consistent
      with the literature of greater repositioning-error in people with NS-CLBP than
      healthy subjects.

PMID- 23948826
TI  - Musculoskeletal pain among undergraduate laptop users in a Nigerian University.
AB  - BACKGROUND AND OBJECTIVE: Musculoskeletal disorder is a significant health
      problem affecting adults and young people alike. The prevalence of
      musculoskeletal pain resulting from musculoskeletal disorders is on the increase
      especially with increased use of laptops. This study determined the prevalence of
      musculoskeletal pain among undergraduate students of Obafemi Awolowo University
      (OAU), Ile-Ife who use laptops. MATERIAL AND METHOD: This was a cross-sectional
      study and participants were selected using the non-probability sampling
      technique. The Boston University Computer and Health Survey questionnaire was
      self-administered to 400 undergraduate laptop users. Data were analyzed using
      descriptive statistics of frequency and percentage. RESULTS: Three hundred and
      seventy six out of 400 copies of administered questionnaires were amenable to
      data analysis representing a response rate of 94%. Pain in the shoulder was the
      most reported musculoskeletal complaint from 268 (75.7%) participants. Elbow pain
      was the least common complaint from 132 (37.3%) participants. The prevalence of
      musculoskeletal pain was slightly higher among female students 93 (50.3%) of 185
      and highest among students aged between 24 and 26 years: 60 (37.5%). In addition,
      the prevalence of musculoskeletal complaints was highest among those who used
      single-strap laptop bags 176 (94.1%). CONCLUSION: There is a high prevalence of
      musculoskeletal pain among undergraduate laptop users in OAU and shoulder pain
      was the most commonly reported.

PMID- 23948827
TI  - On the relationship between pain intensity and postural sway in patients with non
      specific neck pain.
AB  - INTRODUCTION: Increased center of pressure excursions are well documented in
      patients with non-specific neck pain. While a linear relationship between pain
      intensity and postural sway has been described in low back pain patients, no such
      investigation has been conducted in adults with non-specific neck pain. METHODS:
      Seventy patients with non-specific neck pain and a matching number of healthy
      controls were enrolled. Center of pressure parameters were measured by three
      static bipedal standing tasks of 90 sec duration each with eyes closed on a force
      platform. The pain intensity was assessed by a numeric rating scale (NRS), an
      equal number of patients (n=10) was enrolled per pain score. RESULTS: The results
      confirmed an increased postural sway in pain sufferers compared to healthy
      controls. In addition, a significant and linear increase in postural sway was
      observed with higher pain ratings. Statistically significant changes in sway were
      reached with an incremental change in NRS scores of two to three points.
      DISCUSSION AND CONCLUSIONS: Mean velocity and sway area are closely related to
      self-reported pain scores in neck pain patients. This relationship has
      implications for clinical applications such as an objective monitoring tool for
      patients under treatment or rehabilitation.

PMID- 23948828
TI  - The transitional pattern of pain and disability, from perceived pain to sick
      leave. Experience from a longitudinal study.
AB  - OBJECTIVES: To investigate the prospective value of the transitional and dynamic
      patterns of pain disability over time on sick leave in chronic recurrent
      back/neck pain cases. METHODS: The material used was based on a longitudinal
      study with three repeated measurements. The graded Chronic Pain Scale was used to
      assess levels of pain disability. The relationship between the transitional
      patterns of the pain disability score (ten defined states of decrease, increase
      or no change, between two time points) and sick leave was analyzed for 909
      chronic/recurrent cases in three different models using logistic regression.
      RESULTS: Those with high level of pain disability have a more transitional
      pattern and their pain level changed during the time period studied. When
      adjusting for age, gender, education and previous sick leave, the final model
      indicated that the current level of pain disability was a risk factor in taking
      sick leave. The likelihood of sick leave was highest in the transition of pain
      into the highest levels of disability, independent of past disability level of
      pain. Earlier sick leave remained as an important predictor of sick leave.
      CONCLUSIONS: From a clinical and prognostic perspective the probability of sick
      leave will be different and can be predicted based on previous sick leave but not
      from former history of pain disability level or its transitional pattern.

PMID- 23948829
TI  - Lumbar facet joint orientation and osteoarthritis: a cross-sectional study.
AB  - BACKGROUND AND OBJECTIVE: The association between facet orientation, tropism
      (asymmetry of the facet angles) and facet joint osteoarthritis (OA) has been
      previously reported, however, it is necessary to confirm the association in other
      samples. Our aim was to evaluate the association between facet orientation,
      tropism, and facet joint OA in an Israeli sample. METHODS: One hundred and fifty
      low back and abdominal CTs of 82 males (mean age 61.74 +/- 12.99) and 68~females
      (mean age 59.51 +/- 11.74,) were evaluated in a cross-sectional study. Facet
      joint OA was evaluated at the L4-L5 spinal level using a 4-graded scale. The
      association between facet joint OA, facet orientation and tropism was examined
      using multiple logistic regressions adjusted for age and sex. RESULTS: Facet
      orientation showed a statistically significant association with facet joint OA on
      the right side (p=0.009) and in a model where both sides were combined (p=0.003).
      Facet joints with OA were more sagittally oriented. Tropism was not associated
      with facet joint OA on either side (p=0.251 for right and 0.609 for the left
      side), or in a combination of both sides (p=0.482). CONCLUSIONS: We confirm a
      significant association between sagittal orientation and OA of the lumbar facet
      joints at level L4-L5. Facet tropism was not associated with facet joint OA.
      Additional longitudinal studies are needed to understand the causal relationship
      between facet joint orientation and OA.

PMID- 23948830
TI  - The effects of strengthening and high-impact exercises on bone metabolism and
      quality of life in postmenopausal women: a randomized controlled trial.
AB  - BACKGROUND AND OBJECTIVE: The aim of this prospective, randomized controlled 6
      month interventional trial was to investigate the effects of strengthening and
      high-impact exercise training on bone mineral density (BMD), bone turnover
      markers and health-related quality of life (HRQoL) in postmenopausal women.
      MATERIAL AND METHODS: Forty-two eligible postmenopausal women with osteopenia who
      referred to our outpatient clinics were included in the study and allocated
      equally to three groups receiving strengthening exercise, high-impact exercise or
      no exercise (control). The supervised training program consisted of a one-hour
      exercise session three times a week for six months. BMD at the L1-L4 and femoral
      neck, serum bone turnover markers (osteocalcin, OC; N-telopeptides of type I
      collagen, NTx) and HRQoL were measured at the beginning and sixth months.
      RESULTS: There was a significant increase in the BMD at the lumbar spine
      (p=0.017) and femoral neck (p=0.013) in the high-impact group compared to the
      strengthening and control groups. Serum OC (p=0.033) increased, and NTx (p=0.034)
      decreased significantly only in the high-impact group. HRQoL improved
      significantly in both training groups (p< 0.001). CONCLUSIONS: Our data suggest
      that 6-month supervised high-impact exercise training can be effective in
      prevention of bone loss at lumbar spine and femoral neck. These data also
      indicate that both supervised training programs improve HRQoL in postmenopausal
      women.

PMID- 23948831
TI  - Long latency reflex response of superficial trunk musculature in athletes with
      chronic low back pain.
AB  - BACKGROUND AND OBJECTIVES: Incidence of Low Back Pain (LBP) in athletes is as
      high as 30%. Patients with LBP show altered postural and neuromuscular responses
      to various functional tasks. The objective of the study was to compare long
      latency reflex response (occurring between 40 to ~ 100 ms duration) in athletes
      with chronic LBP with asymptomatic athletes. METHODS: Surface electromyography
      (EMG) of superficial trunk muscles - Rectus Abdominis (RA) and Erector Spinae
      (ES) were studied in athletes with chronic LBP (n=24) and asymptomatic athletes
      (n=25). Perturbations were introduced in standing both expectedly and
      unexpectedly. The latency of onset and the Root Mean Square (RMS) amplitudes
      within the reaction duration were compared between the two groups. RESULTS: The
      latency of onset was delayed in Unexpected perturbations but no change was
      observed in Expected tasks. The mean RMS amplitudes were significantly lower in
      both tasks for RA and in the Expected task for ES (p< 0.05). CONCLUSION: Chronic
      LBP athletes exhibit a delay in onset latency to Unexpected perturbations and
      reduced long latency response amplitudes to perturbation tasks compared to
      asymptomatic athletes. These changes could predispose athletes to recurrent low
      back pain and further injury.

PMID- 23948832
TI  - Do new diagnostic criteria for fibromyalgia provide treatment opportunity to
      those previously untreated?
AB  - BACKGROUND AND OBJECTIVES: It has been known that tender points detected by ACR
      1990 criteria alone might not describe the essence of fibromyalgia, so
      preliminary diagnostic ACR 2010 criteria was developed. Since there has been no
      clear evidence exist examining the concordance rates and sensitivity to treatment
      of these two criteria comparatively, we aimed to shed light on this ambiguity.
      MATERIAL AND METHODS: [corrected] One hundred patients with widespread pain were
      studied. Fulfillment of both criteria was determined at baseline, at 3th and 12th
      months. Sensitivity and specificity values were identified. The relationship
      between Fibromyalgia Impact Questionnaire and components of two criteria was
      detected by pearson correlation. And the concordance rate was evaluated by kappa
      coefficient. RESULTS: At the 1st visit (baseline), two criteria were concordant
      in 48.5% (n=49) of cases (kappa=0.43[95%CI.0.22,0.58]). However, the concordance
      was present in only 25(25%) of the subjects (kappa=0.29[95%CI:0.12,0.36]) at the
      end of the study. After 1 year of follow-up, the sensitivity of ACR 2010 was
      higher than that of ACR 1990 (0.88; 0.56 respectively) (p< 0.05). CONCLUSION: ACR
      2010 criteria is more sensitive than ACR 1990 both at first diagnosis and after 1
      year of follow-up. So; it enables to diagnose and may give oppurtunity to treat
      more underdiagnosed FM patients.

PMID- 23948833
TI  - Arachnoiditis ossificans in a patient with ankylosing spondylitis, syringomyelia,
      and a history of spinal surgery.
AB  - BACKGROUND AND OBJECTIVE: In this article, we describe a patient unusual
      presenting with both arachnoiditis ossificans and syringomyelia. We have reviewed
      the patient's evaluation, surgery, and treatment. CASE DESCRIPTION: This patient
      developed paraparesis following thoracolumbar spinal surgery to treat kyphosis
      secondary to ankylosing spondylitis. RESULTS: We performed a T9-T11 total
      laminectomy, drained the cyst, dissected and removed the calcified plaques
      posterior to the cord, and decompressed the neural structures. CONCLUSION:
      Symptomatic arachnoiditis ossificans (AO) a rare clinical manifestation is
      characterized by the calcification or ossification of the spinal arachnoid. The
      occurrence of AO with syringomyelia is rare. To date, a few cases with both AO
      and ankylosing spondylitis have been reported.

PMID- 23948834
TI  - Reliability and validity of the Turkish version of the knee injury and
      osteoarthritis outcome score-physical function short-form (KOOS-PS).
AB  - BACKGROUND: The Knee injury and Osteoarthritis Outcome Score-Physical function
      Short-form (KOOS-PS) is a disease-specific questionnaire that can be used to
      evaluate physical function in patients with knee problems and it has not been
      adapted to Turkish language. OBJECTIVE: The purpose of the present study was to
      adapt the KOOS-PS to the Turkish language and to evaluate the psychometric
      properties of the Turkish version of the KOOS-PS in patients with primary knee
      osteoarthritis. METHODS: The translation from the source language to the target
      language, synthesis, back-translation, revision and pre-test stages were
      performed. A total of eighty patients participated in the study. Internal
      consistency was tested by Cronbach's alpha, test-retest reliability was tested by
      the intra-class correlation coefficient (ICC). Construct validity was
      investigated with Spearmann's rank correlation coefficient and correlations of
      the KOOS-PS with the WOMAC and Lequesne osteoarthritis indexes and with the
      duration of complaints, radiological grade and range of flexion were assessed for
      this purpose. RESULTS: Internal consistency was good, with a Cronbach's alpha of
      0.904 and an ICC value of 0.839 certifying that the Turkish KOOS-PS is a reliable
      tool. Spearman's rank correlation coefficients between the KOOS-PS and the
      overall WOMAC (r=0.764), WOMAC-physical function (r=0.754), WOMAC-pain (r=0.706),
      overall Lequesne (r=0.775), Lequesne-daily living activities (r=0.737) and
      Lequesne-pain (r=0.716) were high. Moderate correlations were found between the
      WOMAC-stiffness, Lequesne-walking distance and KOOS-PS (r=0.599 and 0.528,
      respectively). CONCLUSIONS: The Turkish KOOS-PS was found to be reliable and
      valid for patients with primary knee osteoarthritis.

PMID- 23948835
TI  - Exploration of the validity and reliability of the "backache disability index"
      (BADIX) in patients with non-specific low back pain.
AB  - BACKGROUND AND OBJECTIVES: In clinical examinations of a patient with non
      specific low back pain (LBP), there is a need to dispose over a valid and quick
      to perform rating system. The "Backache Disability Index" for LBP or BADIX
      includes rating of 5 trunk movements in erect position and a "Morning Back
      Stiffness" score, whereof the sum gives the BADIX (max. 20 points). The objective
      of this study was to explore the reliability, responsiveness and concurrent
      validity of the BADIX. Patients with LBP (n=100) were randomly assigned into a
      "control" group (n=40) in function of validity studies, and a "treatment" group
      (n=60) in function of responsiveness studies. The treatment group underwent two
      weekly sessions of in total 30 minutes of deep cross-friction on the thoraco
      lumbar Erector spinae and gluteals. All patients completed the Oswestry
      Disability Questionnaire validated Dutch version (ODQ), the McGill Pain
      Questionnaire (MPQ). The impairment examination consists, besides current
      orthopaedic and neurologic examinations, of the new BADIX scoring system.
      RESULTS: In our study the retest reliability after 3 days of the BADIX was
      perfect (n=039, r=0.95). A good correlation (p < 0.001) was found between BADIX
      at baseline, and Oswestry Disability Index (ODI) (n=93, r=0.76), and McGill
      Quality of Life Index (r=0.74). Similar discriminative ability and effect size of
      measures was found for BADIX and ODI (n=54). It is proposed that the minimal
      detectable change should be equal or more than 2 points. CONCLUSIONS: The
      "Backache Disability Index" appears to be a reliable and a valid assessment tool
      of morning stiffness and restricted spinal movements, and discriminates between
      successful and unsuccessful treatment outcome. The BADIX will allow patients to
      take snapshots of their daily treatment evolution, save them on their computer or
      tablets (apps) and share the results with their doctors and/or therapists.

PMID- 23948836
TI  - The relationship of median nerve F-wave parameters with severity and subtypes of
      carpal tunnel syndrome.
AB  - PURPOSE: F-wave analysis may help affirm or disprove a compression neuropathy. In
      this study we have analysed the effects of focal median nerve injury on F wave in
      Carpal Tunnel Syndrome (CTS). METHOD: We studied 57 patients (100 hands) with
      clinical and electrophysiological CTS and 31 (62 hands) healthy subjects. Median
      nerve F-waves were evaluated following 10 supramaximal stimuli and recording from
      abductor pollicis brevis muscles. Minimum, maximum, and mean F-wave latencies,
      frequency of the F wave (Fp), chronodispersion (F<formula>_{CD}</formula>), mean
      F/M amplitude ratios (mF/M-amp) and F-wave conduction velocity (FwCV) were
      evaluated. RESULTS: The CTS patients showed prolonged F-wave latencies, decreased
      Fp, and an increase of the F<formula>_{CD}</formula> as compared with normative
      values. Absent F wave was presented in 8 of 34 hands (23.5%) with severe CTS
      patients. In the severe group, the FwCV was significantly slower (p< 0.001) and
      the mF/M-amp was significantly higher (p< 0.001) than that of mild and moderate
      groups, respectively. Also, the mF/M-amp was significantly greater and Fp was
      lower in the axonal type than in the demyelinating type. The
      F<formula>_{CD}</formula> was not different among groups. A strong positive
      correlations between mMDL with Fmin (r=0.81, p< 0.000), Fmean (r=0.80, p< 0.000)
      and Fmax (r=0.71, p< 0.000) were revealed. CONCLUSION: Results support the
      differing effects of demyelinating and axonal injury on F-waves and suggest that
      the mF/M-amp ratio and FwCV, which is influenced by neuronal damages in the
      distal segment of the median nerve, is useful in the discrimination of CTS
      severity.

PMID- 23948837
TI  - Michigan Hand Outcomes Questionnaire in rheumatoid arthritis patients:
      relationship with disease activity, quality of life, and handgrip strength.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the clinical
      relevance of Michigan Hand Outcomes Questionnaire (MHQ) in patients with
      rheumatoid arthritis (RA) and to evaluate the relationship between MHQ and
      disease activity, quality of life (QL), and handgrip strength separately.
      MATERIAL AND METHOD: Eighty RA were included in the study. Disease activity is
      evaluated with Disease Activity Score 28 (DAS28), pain is evaluated with Visual
      Analog Scale (VAS). The Disabilities of Arm, Shoulder and Hand (DASH), MHQ, Short
      Form 36 (SF-36), and Health Assessment Questionnaire (HAQ), Arthritis Impact
      Measurement Scales-hand and finger function scale-2 (AIMS-2) were completed by
      all patients. Hand muscle strength (HMS) was measured with a hand-held
      dynamometer. RESULTS: The MHQ moderately correlated with DAS28. When the patients
      were grouped according to three disease activity measurements, DASH scores were
      significantly higher with higher disease activity and MHQ scores were
      significantly lower with higher disease activity. A high correlation was found
      between MHQ total and HAQ, AIMS-2. The SF-36 scores were correlated with MHQ
      scores. CONCLUSIONS: The MHQ scores correlate with disease activity indices,
      functional disability, QL and DASH. The clinical relevance of MHQ, like DASH, is
      high and both questionnaires can be used effectively.

PMID- 23948838
TI  - Does the presence of a vertical barrier influence sagittal spinal curvature or
      range of motion in young females?
AB  - BACKGROUND AND OBJECTIVES: Lifting presents a significant risk for the
      development of low back pain. It is not known what effect lifting from a
      supermarket shopping trolley has on sagittal spinal curvature. The aim of this
      study is to determine the effect of lifting from a shopping trolley on sagittal
      spinal curvature. METHODS: Fifteen female subjects (height 1.67 +/- 0.04 m,
      weight 64.3 +/- 5.0 kg) completed lifts of 9 kg from a shopping trolley and a
      surface matched for height whilst sagittal spinal curvature was measured using
      Qualysis motion analysis system. Seven retro-reflective markers were placed along
      spine with angle between three markers representing regional curvature. No
      constraints on lifting technique were instigated. RESULTS: Results demonstrate no
      difference in sagittal range of motion or spinal curvature across the two lifts.
      A small but significant difference in knee flexion angle was observed. These
      results demonstrate that the chosen lifting strategy was not influenced by the
      constraint imposed by the shopping trolley. Furthermore the function of knee
      flexion did not result in change in sagittal curvature during the lifts.
      CONCLUSION: Lifting from a shopping trolley has no effect of sagittal spinal
      curvature.

PMID- 23948839
TI  - Pain, fear of falling and stair climbing ability in patients with knee
      osteoarthritis before and after knee replacement: 6 month follow-up study.
AB  - OBJECTIVES: (1) to evaluate the change in time of pain, stair climbing ability
      and fear of falling (FOF), (2) to determine the association between pain, stair
      climbing ability and FOF for patients with knee osteoarthritis (OA) following the
      knee replacement over the course of six months, (3) and to compare the results
      with healthy controls in terms of stair climbing ability and FOF. METHODS:
      Fifteen female healthy controls and 21 female consecutive subjects who were
      scheduled to undergo primary bilateral knee replacement for the treatment of knee
      OA were involved. Pain, stair climbing ability and FOF were assessed with a
      numerical pain rating scale, Going up and Down Scale (GUDS) and Tampa Scale for
      Kinesiophobia (TSK) at pre-surgery and discharge. After discharge, patients were
      asked to answer the outcome measures at 2, 4, 8, 12 and 26 week by phone.
      RESULTS: Patients had significantly improvement in the postoperative 26-week
      scores of pain (p< 0.001), stair ability (p< 0.001), and FOF (p=0.006) compared
      with the preoperative scores. There was also decreased pain at 4.week, improved
      stair ability at 8.week, and delayed improvement at FOF in patients. While
      patients had significantly worse stair ability than controls preoperatively (p<
      0.001), the difference was not significant at postoperative 26-week (p=0.561). A
      positive significant correlation was found between the stair ability, FOF and
      pain scores (p< 0.001). CONCLUSION: It would be reasonable to consider that FOF
      control is potentially useful for preventing severe functional limitation in
      stair climbing for subsequent knee OA before and early after the surgery.

PMID- 23948840
TI  - Hamstring muscle length and lumbar lordosis in subjects with different lifestyle
      and work setting: comparison between individuals with and without chronic low
      back pain.
AB  - BACKGROUND AND OBJECTIVES: Shortened hamstring muscle length has been noted in
      persons with low back pain (LBP). Prolonged sitting postures, such as those
      adopted during different work settings and sedentary lifestyle has been
      associated with hamstring shortness and LBP. The purpose of this study was to
      investigate the effect of lifestyle and work setting on hamstring length and
      lumbar lordosis in subjects with and without LBP and to identify the relationship
      between hamstring muscles length and lumbar lordosis in individuals with
      different lifestyle and work setting. MATERIAL AND METHOD: A total of 508
      subjects between the ages of 20 and 65 were selected. Subjects were categorized
      into two groups of individuals with and without LBP. A questionnaire was used to
      obtain information about the subjects' lifestyle and work setting. Hamstring
      muscle length and lumbar lordosis were measured in all subjects. RESULTS: The
      results showed no significant difference in the number of subjects with different
      work setting or lifestyle in individuals with and without LBP. Hamstring muscle
      length or lumbar lordosis was not affected by type of work setting and lifestyle.
      Our data showed significant difference in hamstring length and no significant
      difference in lumbar lordosis between subjects with and without LBP in all
      categories. Lumbar lordosis was not different between individuals with and
      without hamstring tightness in normal and LBP subjects with different work
      setting and lifestyle. CONCLUSION: The findings of this study did not support the
      assumption that work setting and sedentary lifestyle would lead to hamstring
      tightness in subjects with LBP. It seems that work setting and lifestyle was not
      a contributing factor for hamstring tightness in subjects with LBP.

PMID- 23948841
TI  - A comparison of the posture between young female handball players and non
      training peers.
AB  - OBJECTIVES: To evaluate and compare the posture in young female handball players
      and a group of non-training peers. MATERIAL AND METHODS: 125 handball players and
      135 non-training individuals as a control group. All the subjects were aged 12
      15. Measurements of basic somatic parameters (body height and mass, BMI, fat mass
      and total body water) were taken with an electronic balance 'Tanita'. The posture
      was evaluated using the moire method. We analysed the shape of the spine in the
      sagittal plane and the position of the spine, pelvis and shoulder girdle in terms
      of symmetry. RESULTS: In 13-year-old handball players there was a smaller
      inclination of the thoracolumbar segment and a greater forward tilt of the torso.
      Among the training 15-year-olds, the inclination of the lower back, the sum of
      angles of anteroposterior curvatures and the angle of lumbar lordosis were
      smaller than in their non-training peers. Moreover, a correct pelvic alignment in
      the frontal plane, and pelvis and scapulas asymmetries in the transverse plane
      were more common in handball players. CONCLUSION: The formation of
      anteroposterior curvatures of the spine diversified some of the age groups of
      training and non-training young females. Handball training can affect the quality
      of posture.

PMID- 23948842
TI  - Influence of trunk muscle co-contraction on spinal curvature during sitting.
AB  - BACKGROUND AND PURPOSE: Slumped sitting is known to increase disc pressure and
      aggravate chronic low back pain. In addition, it has been recognized that co
      contraction of the deep spine-stabilizing muscles enhances lumbar segmental
      stability and the sacro-iliac joint. The purpose of this study was to compare the
      electromyographic (EMG) activity of the trunk muscles and the muscle thickness of
      the transverse abdominis (TrA) during slumped sitting with the same parameters
      during co-contraction and investigate how co-contraction influences spinal
      curvature. SUBJECTS AND METHODS: Nine healthy male volunteers participated in the
      study. EMG signals were recorded during both sitting postures. In order to
      measure the muscle thickness of the TrA, ultrasound images were captured. While
      the subjects performed both sitting postures, spinal curvature was measured using
      a hand-held device. RESULTS: Significantly more activity of the trunk muscles,
      with the exception of the rectus abdominis muscle, and significantly greater
      muscle thickness of the TrA were observed during co-contraction of the trunk
      muscles than during slumped sitting. Co-contraction also resulted in
      significantly increased lumbar lordosis and a greater sacral angle when compared
      to slumped sitting. CONCLUSION: In this study, it was demonstrated that the
      instructions given to the subjects on co-contraction of the trunk muscles during
      sitting increased muscle activity with the exception of the rectus abdominis
      muscle, muscle thickness of the TrA, and lumbar lordosis.

PMID- 23948843
TI  - Groin pain and iliopsoas bursitis: always a cause-effect relationship?
AB  - BACKGROUND AND OBJECTIVE: Iliopsoas bursitis (IB) is characterized by
      inflammation and enlargement of the iliopsoas bursa. Although this condition is
      often associated with degenerative or inflammatory arthritis, infections, trauma,
      overuse and impingement syndromes, osteonecrosis and hip replacement, the
      pathogenesis of IB remains uncertain. We present a case report of IB associated
      with moderate hip osteoarthritis (HOA). METHODS: We present a case report of a 73
      year-old man with chronic left hip pain that did not respond to conservative
      treatments. An ultrasonography examination of the left hip revealed fluid-induced
      distension of the iliopsoas bursa, which was treated with aspiration followed by
      a corticosteroid-anesthetic injection. RESULTS: At the 30-day follow-up, despite
      an initial improvement in the patient's symptoms, both the pain and functional
      limitation returned, though not in association with bursa distension. The patient
      therefore underwent a total hip arthroplasty, which fully relieved the symptoms.
      CONCLUSION: We hypothesize that iliopsoas bursitis may, when associated with
      other pathological conditions, not be the only source of pain. It should,
      nevertheless, be considered for differential diagnosis purposes.

PMID- 23948844
TI  - A case study of unusual benign osseous lesion of the L5 lamina.
AB  - BACKGROUND: The differential diagnosis of benign-appearing posterior element
      lesions is complex. OBJECTIVE: To explore the etiology of an unusual benign
      lesion found on the lamina of L5 described in a case report. METHODS: Case
      report. The patient's medical, surgical and imaging histories as well as medical
      literature were reviewed. RESULTS: A 35-year old male complained of low back pain
      radiating to both legs for 5 months. Abdominal CT scan 1 year prior as well as
      post symptom-onset CT and MRI showed a well-corticated lesion lateral to the
      spinous process of L5. After failed rehabilitation and injection, operation
      revealed normal cortical bone. Pain was not markedly relieved post-operatively.
      CONCLUSION: The pre-surgical differential diagnosis of this lesion included
      osteosarcoma and osteoid osteoma, however benign pathological results suggest the
      possibility of atypical spina bifida occulta, Baastrup changes, atypical
      sacralization of L5, or a resolved fracture with heterotopic ossification.

PMID- 23948845
TI  - The efficiency of corrective exercise interventions on thoracic hyper-kyphosis
      angle.
AB  - BACKGROUND AND OBJECTIVE: Corrective exercise interventions are often utilized to
      manage subjects with thoracic hyper-kyphosis, yet the quality of evidence that
      supports their efficiency is lacking. In this study, the efficacy of local and
      comprehensive corrective exercise programs (LCEP and CCEP) on kyphosis angle was
      evaluated. MATERIAL AND METHOD: A prospective, randomised controlled design was
      used in the present study. Sixty patients with postural hyper-kyphosis deformity
      (? 42 degrees ) entered the study for 12 weeks. Subjects were randomly assigned
      to a LCEP (n=20), CCEP (n=20), or Control groups (n=20). Pre- and post
      participation levels of kyphosis angle were measured by flexicurve ruler.
      RESULTS: Both the LCEP and CCEP groups demonstrated statistically significant
      reductions in thoracic kyphosis angle compared to the control group (p=0.001).
      Furthermore, based on Cohen's d-value, the efficiency of CCEP was larger than
      LCEP. CONCLUSIONS: Considering the extremely large effect size of the CCEP, we
      recommend that this program be used in the correction of postural hyper-kyphosis
      deformity in future.

PMID- 23948846
TI  - Effects of the high-power pain threshold ultrasound technique in the elderly with
      latent myofascial trigger points: a double-blind randomized study.
AB  - BACKGROUND AND OBJECTIVE: The high-power pain threshold ultrasound (HPPTUS)
      technique has been introduced as a novel treatment method in patients with
      myofascial trigger points (MTrPs). The aim of the current study was to compare
      the therapeutic effects of HPPTUS with those of the conventional ultrasound
      technique in elderly patients with latent MTrPs on the upper trapezius muscles of
      at least 1 side. MATERIAL AND METHODS: Forty-one participants received 8
      treatment sessions with conventional ultrasound (n=19) or with the HPPTUS
      technique (n=22) for 4 consecutive weeks. Outcome variables included visual
      analog scale (VAS) scores, pressure pain threshold (PPT), and range of motion
      (ROM). The data were analyzed using repeated analysis of variance (ANOVA)
      measurements. RESULTS: The VAS scores recorded 1, 2, 3, and 4 weeks after HPPTUS
      were significantly lower than the baseline scores in both groups. The ROM (after
      3 and 4 weeks) and PPT (after 4 weeks) values also significantly increased from
      their baseline values in both groups. On comparing the techniques, there were no
      significant differences in the VAS (p=0.296), PPT (p=0.768), and ROM (p=0.822)
      values, although both techniques showed therapeutic effects for 4 weeks (p <
      0.001). CONCLUSION: The results indicate that the HPPTUS technique in same manner
      as treatment of active MTrPs is not superior to the conventional ultrasound
      technique in the treatment of the elderly patients with the latent MTrPs.

PMID- 23948847
TI  - Chronic ankle instability alters eccentric eversion/inversion and
      dorsiflexion/plantarflexion ratio.
AB  - OBJECTIVE: To determine if the eccentric evertor/invertor and dorsiflexor/plantar
      flexor ratio are altered in subjects with chronic ankle instability. METHODS:
      Twenty chronic ankle instability (CAI) subjects as an experimental group, and
      twenty healthy subjects as a control group, were matched in age, gender, and
      activity level. CAI subjects have a history of at least one ankle sprain and
      repeated episodes of giving way were included in CAI group. Subjects with no
      prior history of ankle injury were included in the control group. Ankle
      evertor/invertor and dorsiflexor/plantar-flexor muscles eccentric torque ratios
      were measured using the eccentric muscle contraction at angular velocities 60 and
      120 degrees /s. RESULTS: Analysis of variance revealed that the eccentric
      contraction eversion/inversion ratio of CAI group was significantly lower than
      normal group ratio at angular velocities 60 and 120 degrees /s (p=0.041 and
      0.012) respectively. The eccentric contraction dorsiflexion/plantarflexion ratio
      of CAI group was significantly higher than normal group ratio at both angular
      velocities (p=0.036 and 0.013) respectively. Moreover, at angular velocities of
      60 degrees /s and 120 degrees /s a deficit in inversion and eversion eccentric
      torques were identified in CAI group (p=0.000), plantarflexion torque deficit of
      CAI group (p=0.034 and 0.028), respectively, and no deficit was identified for
      dorsiflexion torque of CAI group (p=0.595 and 0.696) respectively. CONCLUSION:
      Chronic ankle instability increases the dorsiflexion/plantarflexion muscles
      torque ratio and decreases the eversion/inversion ratio at angular velocities 60
      and 120 degrees /s. Therefore, the restoration of a normal eccentric inversion,
      eversion, and plantarflexion strength may prevent recurrent lateral ankle
      ligament sprain.

PMID- 23948849
TI  - The study of the variability of anticipatory postural adjustments in patients
      with recurrent non-specific low back pain.
AB  - BACKGROUND AND OBJECTIVES: Intrinsic variability is present in all actions,
      including repetitive tasks. The aim of this study was to evaluate the variability
      of anticipatory postural adjustments (APAs) of trunk muscles in participants with
      low back pain (LBP). MATERIAL AND METHOD: The study included 21 participants with
      recurrent non-specific LBP (15 men, 6 women) and 21 healthy volunteers. Standard
      deviation of electromyographic activity of the external oblique (EO), transverse
      abdominis/internal oblique (TrA/IO), and erector spinae (ES) muscles onset
      relative to deltoid muscle onset was recorded in 75 rapid arm flexions, and the
      correlation with the participants' avoidance belief (the FABQ score) and
      disability (the Roland-Morris Questionnaire score) was statistically analyzed.
      RESULTS: participants with LBP exhibited less variability in timing of APAs of
      the TrA/IO muscle compared with the control group (P=0.047). The timing of APAs
      of the TrA/IO muscle was significantly correlated with the FABQ score (P=0.006).
      There was no significant correlation between this variable and disability
      (P=0.09). Decrease in variability of the timing of APA of the EO (P=0.45) and ES
      (P=0.6) muscles was not significant. CONCLUSION: The variability of the postural
      responses of participants with LBP decreased. Restoring variability in postural
      control responses might be a goal in rehabilitating these patients.

PMID- 23948848
TI  - Effects of a stabilization exercise program in functionality and pain in patients
      with degenerative spondylolisthesis.
AB  - OBJECTIVE: To determine the effects of stabilization exercises on pain and
      function in patients with degenerative spondylolisthesis. STUDY DESIGN:
      Nonrandomized clinical trial, with 6 months of follow up. METHODS: Twenty
      patients over 50 years of age with degenerative spondylolisthesis underwent a 6
      month, home-based training program of stabilization exercises. We applied
      functional and pain scales (Visual Analogue Scale [VAS] and Oswestry Disability
      Index [ODI]), and conducted an isokinetic trunk test. Statistical analysis
      included a T test for quantitative variables, a chi-squared test for qualitative
      data, and Pearson correlations. The significance alfa level was 0.05. RESULTS:
      Both pain and Oswestry Index scores were significantly decreased. Initial and
      final VAS "back pain" results were 63.50 +/- 18.05 mm and 43.4 +/- 22.09
      (p=0.007) respectively. Initial and final VAS "sciatic pain" results were 53.65
      +/- 29.03 mm and 36.65 +/- 27.21 (p=0.035) respectively. Oswestry Index at the
      beginning of the study was 30.35 +/- 15.6%, decreasing to a final 20.15 +/- 13.6%
      (p=0.007). The results of VAS and ODI scores correlated significantly with
      improvement in the isokinetic test. CONCLUSION: Lumbar stabilization exercises
      could be an effective treatment option in controlling pain and improving function
      in patients with degenerative spondylolisthesis. Further investigation with
      randomized controlled trials is necessary to obtain confirmation of these
      results.

PMID- 23948850
TI  - Identifying factors associated with low back pain among employees working at a
      package producing industry.
AB  - BACKGROUND: The purpose of this study was to identify factors associated with Low
      Back Pain (LBP) among employee working at a package producing industry. METHODS:
      A sample of 111 male blue-collar workers, between the ages of 18 to 50 years old
      and 31 white-collar workers between the ages of 17 to 50 years old completed a
      questionnaire which included demographic data, educational level, participation
      in sports activities, activity, postural habits, smoking, work conditions lifting
      and bending activities during the workday strenuous arm position and questions
      related with low back pain (LBP). The isometric strength of back muscles were
      measured using a dynamometer. RESULT: The prevalence of LBP during the past 12
      months was 55.9% for blue-collar workers and 51.6% for white-collar workers. The
      chi-square and t-test analysis showed statistically significant relations between
      LBP and smoking, number of years spent working in the last job, lifting
      activities between the ages of 30-34 years old. The incorrect standing and
      sitting posture of the blue-collar workers and the sitting posture with bending
      forward on the table of the white-collar workers were significantly related with
      LBP (p< 0.05). CONCLUSIONS: Our results identified the risk factors of LBP in a
      package producing company. The protective approaches aiming to avoid the risk
      factors could decrease the low back pain prevalence that increases each year
      passed worked at the company.

PMID- 23948851
TI  - Aggressive vertebral hemangioma as a rare cause of myelopathy.
AB  - Vertebral hemangiomas (VHs) are common lesions in the adult population. They are
      usually asymptomatic and found incidentally on radiological imaging. New-onset
      back pain followed by subacute progression of thoracal myelopathy is the most
      common presentation in patients with neurological deficit. Differential diagnoses
      would include metastasis, multiple myeloma, lymphoma, Paget disease, osseous
      tumors such as Ewing sarcoma or hemangioblastoma and blood dyscrasia. We present
      a 41 year-old-male patient with thoracal VH causing myelopathy that completely
      improved after rehabilitation program with embolization and vertebroplasty
      procedures. 

PMID- 23948852
TI  - An effective coaching intervention for people with low recovery expectations and
      low back pain: a content analysis.
AB  - BACKGROUND: A health coaching intervention in addition to usual physiotherapy
      care increased recovery expectation and activity in people with non-chronic NSLBP
      and low recovery expectation. OBJECTIVE: We aimed to fully describe the coaching
      intervention to allow replication and enable a deeper understanding of the
      mechanisms behind health coaching in this setting. METHODS: A qualitative
      analysis was conducted using notes taken by the coach during the health coaching
      intervention. Two researchers independently applied open coding and content
      analysis, using the factors of low recovery expectation identified in a previous
      qualitative investigation as a framework. RESULTS: For the majority of
      participants coaching rapidly progressed to goal setting and action planning,
      with less time spent on increasing the importance and confidence to return to
      activity. The factors of the person, progression, pain, performance and treatment
      were addressed across all phases of the coaching intervention. CONCLUSION: This
      effective health coaching intervention for people with non-chronic NSLBP and low
      recovery expectation concentrated on goal setting and action planning and
      addressed the essential factors of recovery expectations. This study suggests
      that coaching interventions are likely to be different in this population
      compared to similar interventions in chronic conditions due to pre-existing
      levels of readiness to change.

PMID- 23948853
TI  - Site-specific immobilization of biomolecules by a biocompatible reaction between
      terminal cysteine and 2-cyanobenzothiazole.
AB  - We report herein a new site-specific microarray immobilization method based on a
      biocompatible reaction between terminal cysteine and 2-cyanobenzothiazole (CBT).
      This immobilization strategy has been successfully applied to anchor small
      molecules, peptides and proteins onto microarrays. 

PMID- 23948854
TI  - Is urinary soluble Fas an independent predictor of non-muscle-invasive bladder
      cancer? A prospective chart study.
AB  - OBJECTIVES: To evaluate whether soluble Fas (sFas) in urine is an independent
      predictor of non-muscle-invasive bladder cancer (NMIBC). METHODS: We performed a
      prospective chart review which included 128 subjects with NMIBC and 88 controls.
      The first morning voided urine sample (10-20 ml) was obtained from preoperative
      patients and controls. Expression levels of sFas in urine were analyzed using
      enzyme-linked immunosorbent assay. Clinical and pathological data, European
      Organisation for Research and Treatment of Cancer (EORTC) risk group category,
      follow-up data and urinary sFas values were gathered from each patient, and each
      prognostic outcome was evaluated. RESULTS: sFas levels were significantly higher
      in the urine of patients with NMIBC than of those without NMIBC (p = 0.000). The
      level was significantly higher in cases with a higher stage or grade or high-risk
      and recurrent disease than in those with a lower stage or grade or low-risk and
      nonrecurrent disease (each p < 0.05). Kaplan-Meier estimates revealed a
      significant difference in time to recurrence based on sFas levels in the urine of
      the NMIBC patients (log-rank test; p = 0.000). On multivariate Cox regression
      analysis, EORTC risk group category (hazards ratio [HR] = 3.250, p = 0.000) and
      urinary sFas level (HR = 1.403, p = 0.015) were the independent predictors of
      NMIBC recurrence. CONCLUSIONS: Our study indicated that urinary sFas assay
      results may help identify NMIBC patients at risk of tumor recurrence. These data
      can be used to design a future follow-up schedule and treatment strategy for
      NMIBC patients.

PMID- 23948855
TI  - Bronsted acid-catalyzed rapid enol-ether formation of 2-hydroxyindole-3
      carboxaldehydes.
AB  - A one-step Bronsted acid-catalyzed synthetic methodology leading to 3
      (alkoxymethylene)indolin-2-ones was developed starting from easily accessible 2
      hydroxyindole-3-carboxaldehydes. The procedure simply involves a treatment of
      differently substituted 2-hydroxyindole-3-carboxaldehydes with various alcohols
      (primary/secondary/tertiary/allyl/propargyl/benzyl) in the presence of a
      catalytic amount of Bronsted acids such as [Formula: see text]-toluenesulfonic
      acid and trifluroacetic acid. A series of 19 indolin-2-one-based enol-ethers were
      synthesized in excellent yields, which implies the general character of our
      methodology. The enol-ethers produced could be used as a useful building block
      for the synthesis of indole-based heterocycles. 

PMID- 23948856
TI  - Using quantum principles to develop independent continuing nursing education
      programs.
AB  - Innovations in health care call for fresh approaches to continuing nursing
      education that support lateral relationships, teamwork, and collaboration. To
      foster this transformation, we devised the following education principles:
      Everyone teaches, everyone learns; embrace probability; information is dynamic;
      and trust professionals to practice professionally. These principles guided the
      development of seven independent, practice-specific, evidence-based continuing
      nursing education programs totaling 21.5 contact hours for casual-status nurses
      who practiced as childbirth educators. The programs were popular, promoted
      teamwork, and increased communication about evidence-based practice. 

PMID- 23948857
TI  - [Acoustic and vestibular effects of superior semicircular canal dehiscence].
AB  - A dehiscence of the superior semicircular canal is associated with many middle
      and inner ear symptoms of varying specificity. Concerning the pathophysiology,
      the way in which these symptoms are connected to a postulated missing bony layer
      of the superior semicircular canal remains to be completely clarified. In
      particular, it is unclear why a bony dehiscence might induce symptoms at all; as
      shown by recent experimental investigations, the natural in vivo coverage of the
      superior semicircular canal by dura, cerebrospinal fluid and brain prevents
      changes in inner ear impedance. Diagnosis of superior semicircular canal
      dehiscence is currently based on a combination of different tests. While cranial
      computed tomography (with its limited visual resolution) has proven to be largely
      unsuitable, ocular vestibular-evoked myogenic potentials (oVEMP) are considered
      an important component of diagnosis. In addition to symptomatic treatment,
      isolated cases also present the option of highly invasive surgical intervention.
      Although the majority of published case reports document positive clinical
      outcomes for operated patients, these procedures are associated with considerable
      perioperative risks. 

PMID- 23948858
TI  - Gelling by heating.
AB  - We exploit the concept of competing interactions to design a binary mixture of
      patchy particles that forms a reversible gel upon heating. Our molecular dynamics
      computer simulation of such a system shows that with increasing temperature the
      relaxation dynamics slows down by more than four orders of magnitude and then
      speeds up again. The system is thus a fluid both at high and at low temperatures
      and a solid-like disordered open network structure at intermediate temperature.
      We further discuss the feasibility of realizing a real material with this
      reversible behavior. 

PMID- 23948859
TI  - Volume-based assessment by (18)F-FDG PET/CT predicts survival in patients with
      stage III non-small-cell lung cancer.
AB  - PURPOSE: We evaluated the prognostic impact of volume-based assessment by (18)F
      FDG PET/CT in patients with stage III non-small-cell lung cancer (NSCLC).
      METHODS: We reviewed 194 consecutive patients with stage IIIA NSCLC treated with
      surgical resection (surgical group) and 115 patients treated with nonsurgical
      therapy (nonsurgical group: 50 stage IIIA, 65 stage IIIB). Metabolic tumour
      volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake
      value (SUVmax) of primary tumours were measured using pretreatment (18)F-FDG
      PET/CT. Overall survival was assessed using the Kaplan-Meier method. The
      prognostic significance of PET parameters and other clinical variables was
      assessed using Cox proportional hazards regression analyses. To evaluate and
      compare the predictive performance of PET parameters, time-dependent receiver
      operating characteristic (ROC) curve analysis was used. RESULTS: In the Cox
      proportional hazards models, MTV (HR=1.27 for a doubling of MTV, P=0.008) and TLG
      (HR=1.22 for a doubling of TLG, P=0.035) were significantly associated with an
      increased risk of death after adjusting for age, gender, histological cell type,
      T stage, N stage, and treatment variables in the surgical group. SUVmax was not a
      significant prognostic factor in either the surgical or nonsurgical group. In the
      time-dependent ROC curve analysis, volume-based PET parameters predicted survival
      better than SUVmax. CONCLUSION: The volume-based PET parameters (MTV and TLG) are
      significant prognostic factors for survival independent of tumour stage and
      better prognostic imaging biomarkers than SUVmax in patients with stage IIIA
      NSCLC after surgical resection.

PMID- 23948860
TI  - Sex-specific gonadal and gene expression changes throughout development in
      fathead minnow.
AB  - Although fathead minnows (Pimephales promelas) are commonly used as a model fish
      in endocrine disruption studies, past studies have not characterized sex-specific
      baseline expression of genes involved in sex differentiation during development
      in this species. Using a sex-linked DNA marker to verify gender, we evaluated the
      expression over time of genes involved in sex differentiation (dmrt1, cyp19a,
      cyp17, star, esr1, ar) in developing fathead minnows (10-45 days post hatch).
      Evaluation of these molecular markers in combination with gender identification
      help us to better understand the mechanisms regulating sex differentiation in
      fathead minnows and how endocrine-disrupting chemicals may alter these processes.

PMID- 23948861
TI  - Light-evoked currents in retinal ganglion cells from dystrophic RCS rats.
AB  - PURPOSE: To study the electrophysiological properties of the light-evoked
      currents in ganglion cells in situations of retinal degeneration. METHODS: We
      investigated light-evoked currents in ganglion cells by performing whole-cell
      patch-clamp recordings from ganglion cells using a retina-stretched preparation
      from Royal College of Surgeons (RCS) rats, a model of retinal degeneration and
      congenic controls at different ages. Pharmacological inhibitors of the AMPA
      receptor (NBQX), GABA receptor (BMI), and sodium channels (TTX) were used to
      identify the components of the light-evoked currents in ON, OFF and ON-OFF
      retinal ganglion cells. RESULTS: We found that the light-evoked currents in
      ganglion cells from control rats were inhibited by NBQX, BMI and TTX, suggesting
      that AMPA receptors, GABA receptors and sodium channels contribute to these
      currents in ganglion cells. However, only AMPA receptor-mediated currents were
      recorded in RCS rats. Light-evoked inward currents were absent in the majority of
      ganglion cells from RCS rats, particularly at the later stages of retinal
      degeneration. At earlier stages of retinal degeneration, we found that both the
      timing and amplitude of light-evoked currents are significantly different in
      ganglion cells from RCS and control rats. CONCLUSIONS: Our study furthers the
      understanding of the electrophysiological characteristics of retinal ganglion
      cells during retinal degeneration, and provides insight into the optimal timing
      for the treatment of retinal degeneration.

PMID- 23948862
TI  - Do high levels of n-3 polyunsaturated fatty acids in cell membranes increase the
      risk of postoperative atrial fibrillation?
AB  - OBJECTIVES: Postoperative atrial fibrillation (POAF) has been associated with an
      inflammatory response to the surgical procedure. n-3 long-chain polyunsaturated
      fatty acids (LC-PUFA) have been proposed for the prevention of POAF. We
      investigated the relationship between the plasma concentration of inflammatory
      mediators, levels of n-3 LC-PUFA in red blood cell (RBC) membrane lipids, and the
      risk of POAF after coronary artery bypass grafting (CABG). METHODS: A total of
      125 patients who underwent CABG were studied. Inflammatory mediators in plasma
      and the content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in
      RBC membranes were assessed. RESULTS: Sixty-two patients (49.6%) developed POAF.
      The POAF group had higher RBC levels of total n-3 LC-PUFA and DHA than did
      patients remaining in sinus rhythm (p < 0.05). Of the inflammatory mediators,
      only postoperative interleukin-6 levels differed, being higher in the POAF group
      (p < 0.05). Inflammatory mediators were not independent predictors of POAF by
      multivariable logistic regression analysis. Higher levels of DHA and total n-3 LC
      PUFA in RBC membranes, measured immediately prior to CABG and on postoperative
      day 3, were linearly associated with an increased risk of POAF (p < 0.05).
      CONCLUSIONS: Our findings suggest that inflammatory mediators are not associated
      with the occurrence of POAF. Interestingly, high n-3 LC-PUFA levels in RBC
      membranes appear to increase the risk of POAF.

PMID- 23948863
TI  - Rapid microfluidic flow hydrogenation for reduction or deprotection of 18F
      labeled compounds.
AB  - We have combined the benefits of both microfluidics and flow hydrogenation to
      provide facile access to previously underutilized reduction and protecting group
      chemistries for PET imaging applications. The rapid removal of an O-benzyl
      protecting group to prepare 2-[(18)F]fluoroquinolin-8-ol and the reduction of a
      nitro group in the synthesis of 4-[(18)F]fluoroaniline were achieved within 3
      minutes. 

PMID- 23948864
TI  - Shockwave therapy differentially stimulates endothelial cells: implications on
      the control of inflammation via toll-Like receptor 3.
AB  - Shock wave therapy (SWT) reportedly improves ventricular function in ischemic
      heart failure. Angiogenesis and inflammation modulatory effects were described.
      However, the mechanism remains largely unknown. We hypothesized that SWT
      modulates inflammation via toll-like receptor 3 (TLR3) through the release of
      cytosolic RNA. SWT was applied to human umbilical vein endothelial cells (HUVECs)
      with 250 impulses, 0.08 mJ/mm(2) and 3 Hz. Gene expression of TLR3, inflammatory
      genes and signalling molecules was analysed at different time points by real-time
      polymerase chain reaction. SWT showed activation of HUVECs: enhanced expression
      of TLR3 and of the transporter protein for nucleic acids cyclophilin B, of pro
      inflammatory cytokines cyclophilin A and interleukin-6 and of anti-inflammatory
      interleukin-10. No changes were found in the expression of vascular endothelial
      cell adhesion molecule. SWT modulates inflammation via the TLR3 pathway. The
      interaction between interleukin (IL)-6 and IL-10 in TLR3 stimulation can be
      schematically seen as a three-phase regulation over time.

PMID- 23948865
TI  - Developing nuclear DNA phylogenetic markers in the angiosperm genus Leucadendron
      (Proteaceae): a next-generation sequencing transcriptomic approach.
AB  - Despite the recent advances in generating molecular data, reconstructing species
      level phylogenies for non-models groups remains a challenge. The use of a number
      of independent genes is required to resolve phylogenetic relationships,
      especially for groups displaying low polymorphism. In such cases, low-copy
      nuclear exons and non-coding regions, such as 3' untranslated regions (3'-UTRs)
      or introns, constitute a potentially interesting source of nuclear DNA variation.
      Here, we present a methodology meant to identify new nuclear orthologous markers
      using both public-nucleotide databases and transcriptomic data generated for the
      group of interest by using next generation sequencing technology. To identify PCR
      primers for a non-model group, the genus Leucadendron (Proteaceae), we adopted a
      framework aimed at minimizing the probability of paralogy and maximizing
      polymorphism. We anchored when possible the right-hand primer into the 3'-UTR and
      the left-hand primer into the coding region. Seven new nuclear markers emerged
      from this search strategy, three of those included 3'-UTRs. We further compared
      the phylogenetic potential between our new markers and the ribosomal internal
      transcribed spacer region (ITS). The sequenced 3'-UTRs yielded higher
      polymorphism rates than the ITS region did. We did not find strong incongruences
      with the phylogenetic signal contained in the ITS region and the seven new
      designed markers but they strongly improved the phylogeny of the genus
      Leucadendron. Overall, this methodology is efficient in isolating orthologous
      loci and is valid for any non-model group given the availability of
      transcriptomic data. 

PMID- 23948866
TI  - Population genetics and phylogenetic relationships of beetles (Coleoptera:
      Histeridae and Staphylinidae) from the Sonoran Desert associated with rotting
      columnar cacti.
AB  - Dozens of arthropod species are known to feed and breed in the necrotic tissues
      (rots) of columnar cacti in the Sonoran Desert. Because the necrotic patches are
      ephemeral, the associated arthropods must continually disperse to new cacti and
      therefore the populations of any given species are expected to show very little
      local genetic differentiation. While this has been found to be true for the
      cactophilic Drosophila, the evolutionary histories and characteristics of other
      arthropods inhabiting the same necrotic patches, especially the beetles, have yet
      to be examined. Here we used nucleotide sequence data from segments of the
      mitochondrial 16S rRNA and cytochrome c oxidase subunit I (COI) genes to examine
      population structure and demographic history of three sympatric beetle species
      (Coleoptera: Histeridae and Staphylinidae) collected on senita cactus
      (Lophocereus schottii) from six widely-separated localities on the Baja
      California peninsula of northwestern Mexico. Two histerids, Iliotona beyeri and
      Carcinops gilensis, and an unidentified staphylinid, Belonuchus sp., showed
      little or no population structure over a broad geographic area on the peninsula,
      consistent with the prediction that these beetles should show high dispersal
      ability. Demographic tests revealed varying levels of historical population
      expansion among the beetle species analyzed, which are discussed in light of
      their ecologies and concurrent biogeographic events. Additionally, phylogenetic
      analyses of COI sequences in Carcinops collected on a variety of columnar cacti
      from both peninsular and mainland Mexico localities revealed several species
      level partitions, including a putative undescribed peninsular species that
      occurred sympatrically with C. gilensis on senita. 

PMID- 23948867
TI  - NF-kappaB acts downstream of EGFR in regulating low dose cadmium induced primary
      lung cell proliferation.
AB  - Apart from cytotoxicity cadmium has no special attributes towards cell's
      physiological function. The role of cadmium with respect to cell growth is still
      under debate. Mitogen activated protein kinase and Ca(2+)/calmodulin dependent
      protein kinase dependent pathways are the two elaborately studied concerning
      cadmium induced cell proliferation. Low concentration of cadmium chloride (2.5
      MUM) was applied to mice primary lung epithelial cells and cell proliferation was
      measured both by cell cycle analysis and Brdu incorporation assay. Effects of
      differential dose of cadmium chloride on lung epithelial cells were evaluated
      morphologically by atomic force microscopy. RT-PCR and western blot altogether
      corroborated the specific signalling pathways concerning cadmium induced lung
      cell proliferation. Cadmium induced lung epithelial cells which over-expressed
      EGFR, were transfected with siEGFR, revealed downstream molecules and RNAi
      induced EGFR silencing. Use of siEGFR effectively prevents expression of
      proinflammatory and cell proliferative markers. Moreover N-acetyl cysteine and
      ascorbic acid mediated inhibition of EGFR and downstream signalling molecules
      indicate the involvement of reactive oxygen species. Exposure to low
      concentration of cadmium promotes the growth of primary mice lung epithelial cell
      by EGFR signalling. We have also transfected the primary lung epithelial cell
      with siRNA against the regulatory subunit of nuclear factor-kappaB (NF-kappaB)
      and the data shows that cadmium induced lung cell proliferation is the effect of
      EGFR mediated NF-kappaB activation.

PMID- 23948868
TI  - Persistent vaginal discharge following proctocolectomy--if there is no fistula,
      what is it?

PMID- 23948869
TI  - Mutation in the seed storage protein kafirin creates a high-value food trait in
      sorghum.
AB  - Sustainable food production for the earth's fast-growing population is a major
      challenge for breeding new high-yielding crops, but enhancing the nutritional
      quality of staple crops can potentially offset limitations associated with yield
      increases. Sorghum has immense value as a staple food item for humans in Africa,
      but it is poorly digested. Although a mutant exhibiting high-protein
      digestibility and lysine content has market potential, the molecular nature of
      the mutation is previously unknown. Here, building on knowledge from maize
      mutants, we take a direct approach and find that the high-digestible sorghum
      phenotype is tightly linked to a single-point mutation, rendering the signal
      peptide of a seed storage protein kafirin resistant to processing, indirectly
      reducing lysine-poor kafirins and thereby increasing lysine-rich proteins in the
      seeds. These findings indicate that a molecular marker can be used to accelerate
      introduction of this high nutrition and digestibility trait into different
      sorghum varieties. 

PMID- 23948870
TI  - Effect of various facial angles and measurements on the ideal position of the
      nasal tip in the Asian patient population.
AB  - IMPORTANCE: Successful surgical correction of nasal tip position requires
      preoperative analysis. Perceived adequate nasal tip position depends on its
      relationship with other facial features. Nasal tip position can be affected by
      the subnasal contour, proportion of facial height, and relative facial size and
      shape. The relation of these factors to the nasolabial angle may not be as
      important as previously believed. OBJECTIVE: To investigate and compare the
      factors affecting the ideal location of the tip of the nose in Asian patients
      using standard photographic measurements. DESIGN: We analyzed measurements of
      profile photographs and compared different factors that affect nasal tip
      location, including the nasofrontal, nasolabial, nasomental, and Legan angles and
      the ratios of the dorsal height to tip projection, the radix height to tip
      projection, the glabella to subnasale, and the subnasale to mentum. SETTING AND
      PARTICIPANTS: One hundred men, 100 women, 20 to 40 years old, seen for
      rhinoplasty at the Department of Otorhinolaryngology, Chosun University College
      of Medicine. MAIN OUTCOME AND MEASURES: Contribution of different facial
      measurements to the ideal nasal tip position. RESULTS: Nasolabial and nasomental
      angles exerted a statistically significant effect on ideal nasal tip position,
      whereas the Legane angle, the ratio of midface to lower face, and the ratio of
      nasal length to lower face did not show significant effects on nasal tip
      position. CONCLUSIONS AND RELEVANCE: The nasolabial and nasomental angles have
      important effects on ideal nasal tip position and should be considered together
      during preoperative evaluation of the location of the nasal tip. Concurrent
      genioplasty should optimize rhinoplasty outcomes in appropriately selected
      patients. LEVEL OF EVIDENCE: NA.

PMID- 23948871
TI  - Ag nanocluster functionalized glasses for efficient photonic conversion in light
      sources, solar cells and flexible screen monitors.
AB  - An ever growing demand for efficient energy conversion, for instance in
      luminescent lamps, flexible screens and solar cells, results in the current
      significant growth of research on functionalized nanomaterials for these
      applications. This paper reviews recent developments of a new class of optically
      active nanostructured materials based on glasses doped with luminescent Ag
      nanoclusters consisting of only a few Ag atoms, suitable for mercury-free white
      light generation and solar down-shifting. This new approach, based solely on Ag
      nanocluster doped glasses, is compared to other alternatives in the field of Ag
      and rare-earth ion co-doped materials. 

PMID- 23948872
TI  - Bandwidth optimization design of a multi degree of freedom MEMS gyroscope.
AB  - A new robust multi-degree of freedom (multi-DOF) MEMS gyroscope is presented in
      this paper. The designed gyroscope has its bandwidth and amplification factor of
      the sense mode adjusted more easily than the previous reported multi-DOF MEMS
      gyroscopes. Besides, a novel spring system with very small coupling stiffness is
      proposed, which helps achieve a narrow bandwidth and a high amplification factor
      for a 2-DOF vibration system. A multi-DOF gyroscope with the proposed weak spring
      system is designed, and simulations indicate that when the operating frequency is
      set at 12.59 kHz, the flat frequency response region of the sense mode can be
      designed as narrow as 80 Hz, and the amplification factor of the sense mode at
      the operating frequency is up to 91, which not only protects the amplification
      factor from instability against process and temperature variations, but also
      sacrifices less performance. An experiment is also carried out to demonstrate the
      validity of the design. The multi-DOF gyroscope with the proposed weak coupling
      spring system is capable of achieving a good tradeoff between robustness and the
      performance. 

PMID- 23948873
TI  - Gyroscope-driven mouse pointer with an EMOTIV(r) EEG headset and data analysis
      based on Empirical Mode Decomposition.
AB  - This paper presents a project on the development of a cursor control emulating
      the typical operations of a computer-mouse, using gyroscope and eye-blinking
      electromyographic signals which are obtained through a commercial 16-electrode
      wireless headset, recently released by Emotiv. The cursor position is controlled
      using information from a gyroscope included in the headset. The clicks are
      generated through the user's blinking with an adequate detection procedure based
      on the spectral-like technique called Empirical Mode Decomposition (EMD). EMD is
      proposed as a simple and quick computational tool, yet effective, aimed to
      artifact reduction from head movements as well as a method to detect blinking
      signals for mouse control. Kalman filter is used as state estimator for mouse
      position control and jitter removal. The detection rate obtained in average was
      94.9%. Experimental setup and some obtained results are presented. 

PMID- 23948874
TI  - Leg edema quantification for heart failure patients via 3D imaging.
AB  - Heart failure is a common cardiac disease in elderly patients. After discharge,
      approximately 50% of all patients are readmitted to a hospital within six months.
      Recent studies show that home monitoring of heart failure patients can reduce the
      number of readmissions. Still, a large number of false positive alarms as well as
      underdiagnoses in other cases require more accurate alarm generation algorithms.
      New low-cost sensors for leg edema detection could be the missing link to help
      home monitoring to its breakthrough. We evaluated a 3D camera-based measurement
      setup in order to geometrically detect and quantify leg edemas. 3D images of legs
      were taken and geometric parameters were extracted semi-automatically from the
      images. Intra-subject variability for five healthy subjects was evaluated.
      Thereafter, correlation of 3D parameters with body weight and leg circumference
      was assessed during a clinical study at the Medical University of Graz. Strong
      correlation was found in between both reference values and instep height, while
      correlation in between curvature of the lower leg and references was very low. We
      conclude that 3D imaging might be a useful and cost-effective extension of home
      monitoring for heart failure patients, though further (prospective) studies are
      needed. 

PMID- 23948875
TI  - Classification of women with and without hip fracture based on quantitative
      computed tomography and finite element analysis.
AB  - We used quantitative computed tomography and finite element analysis to classify
      women with and without hip fracture. Highly accurate classifications were
      achieved indicating the potential for these methods to be used for subject
      specific assessment of fracture risk. INTRODUCTION: Areal bone mineral density
      (aBMD) is the current clinical diagnostic standard for assessing fracture risk;
      however, many fractures occur in people not defined as osteoporotic by aBMD.
      Finite element (FE) analysis based on quantitative computed tomography (QCT)
      images takes into account both bone material and structural properties to provide
      subject-specific estimates of bone strength. Thus, our objective was to determine
      if FE estimates of bone strength could classify women with and without hip
      fracture. METHODS: Twenty women with femoral neck fracture and 15 women with
      trochanteric fractures along with 35 age-matched controls were scanned with QCT
      at the hip. Since it is unknown how a specific subject will fall, FE analysis was
      used to estimate bone stiffness and bone failure load under loading
      configurations with femoral neck internal rotation angles ranging from -30
      degrees  to 45 degrees  with 15 degrees  intervals. Support vector machine (SVM)
      models and a tenfold cross-validation scheme were used to classify the subjects
      with and without fracture. RESULTS: High accuracy was achieved when using only FE
      analysis for classifying the women with and without fracture both when the
      fracture types were pooled (82.9 %) and when analyzed separately by femoral neck
      fracture (87.5 %) and trochanteric fracture (80.0 %). The accuracy was further
      increased when FE analysis was combined with volumetric BMD (pooled fractures
      accuracy, 91.4 %) CONCLUSIONS: While larger prospective studies are needed, these
      results demonstrate that FE analysis using multiple loading configurations
      together with SVM models can accurately classify individuals with previous hip
      fracture.

PMID- 23948877
TI  - Milk consumption throughout life and bone mineral content and density in elderly
      men and women.
AB  - Association between bone mineral density and bone mineral content in old age and
      milk consumption in adolescence, midlife, and old age was assessed. The
      association was strongest for milk consumption in midlife: those drinking milk
      daily or more often had higher bone mineral density and content in old age than
      those drinking milk seldom or never. INTRODUCTION: The role of lifelong milk
      consumption for bone mineral density (BMD) and bone mineral content (BMC) in old
      age is not clear. Here we assess the association between hip BMD and BMC in old
      age and milk consumption in adolescence, midlife, and current old age. METHODS:
      Participants of the Age, Gene/Environment Susceptibility-Reykjavik Study, aged 66
      96 years (N = 4,797), reported retrospective milk intake during adolescence and
      midlife as well as in current old age, using a validated food frequency
      questionnaire. BMC of femoral neck and trochanteric area was measured by
      volumetric quantitative computed tomography and BMD obtained. Association was
      assessed using linear regression models. Differences in BMC, bone volume, and BMD
      in relation to milk intake were portrayed as gender-specific Z-scores. RESULTS:
      Men consuming milk >= once/day during midlife had 0.21 higher Z-scores for BMD
      and 0.18 for BMC in femoral neck (95 % confidence interval 0.05-0.39 and 0.01
      0.35, respectively) compared with < once/week. Results were comparable for
      trochanter. For women the results were similar, with slightly lower differences
      according to midlife milk consumption. For current and adolescent milk
      consumption, differences in Z-scores were smaller and only reached statistical
      significance in the case of BMD for current consumption in men, while this
      association was less pronounced for BMC. CONCLUSIONS: Our data suggest that
      regular milk consumption throughout life, from adolescence to old age, is
      associated with higher BMC and BMD in old age, with no differences seen in bone
      volume. The strongest associations are seen for midlife milk consumption in both
      genders.

PMID- 23948876
TI  - Skeletal findings in the first 12 months following initiation of glucocorticoid
      therapy for pediatric nephrotic syndrome.
AB  - Incident vertebral fractures and lumbar spine bone mineral density (BMD) were
      assessed in the 12 months following glucocorticoid initiation in 65 children with
      nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6
      %) and most patients demonstrated recovery in BMD Z-scores by this time point.
      INTRODUCTION: Vertebral fracture (VF) incidence following glucocorticoid (GC)
      initiation has not been previously reported in pediatric nephrotic syndrome.
      METHODS: VF was assessed on radiographs (Genant method); lumbar spine bone
      mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry.
      RESULTS: Sixty-five children were followed to 12 months post-GC initiation
      (median age, 5.4 years; range, 2.3-17.9). Three of 54 children with radiographs
      (6 %; 95 % confidence interval (CI), 2-15 %) had incident VF at 1 year. The mean
      LS BMD Z-score was below the healthy average at baseline (mean +/- standard
      deviation (SD), -0.5 +/- 1.1; p = 0.001) and at 3 months (-0.6 +/- 1.1; p <
      0.001), but not at 6 months (-0.3 +/- 1.3; p = 0.066) or 12 months (-0.3 +/- 1.2;
      p = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z
      scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p = 0.003). A
      subgroup (N = 16; 25 %) had LS BMD Z-scores that were <=-1.0 at 12 months. In
      these children, each additional 1,000 mg/m(2) of GC received in the first 3
      months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95
      % CI, -0.71 to -0.07; p = 0.017). CONCLUSIONS: The incidence of VF at 1 year was
      low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five
      percent of children had LS BMD Z-scores <=-1.0 at 12 months. In these children,
      LS BMD Z-scores were inversely associated with early GC exposure, despite similar
      GC exposure compared to the rest of the cohort.

PMID- 23948879
TI  - Neprilysin-like activity correlates with CSF-Tau and phospho-tau in patients with
      Alzheimer's disease.
AB  - A relation between amyloid-beta peptide (Abeta) accumulation and neprilysin
      (NEP), an Abeta degrading enzyme, has been proposed but studies of NEP and the
      levels of the pathological hallmarks of Alzheimer's disease (AD), Abeta and tau,
      in cerebrospinal fluid (CSF) are scarce. In this study, we measured the level and
      enzyme activity of NEP in serum and CSF, using a sandwich enzyme-linked
      immunosorbent assay and a fluorescence resonance energy transfer assay,
      respectively, in patients with AD, frontotemporal dementia (FTD), Creutzfeldt
      Jakob disease (CJD), and depression. Results were correlated with the levels of
      CSF AD biomarkers Abeta42, hyperphosphorylated tau (p-tau), and total tau (t
      tau). In serum, we found no differences in NEP-like activity or concentration
      between the groups and there were no correlations between NEP and AD biomarkers.
      In CSF, no influence of age or gender on NEP levels or enzyme activity was seen.
      However, NEP concentration was lower and the specific activity was higher in FTD
      compared to AD. Abeta42 levels in CSF did not correlate with NEP concentration or
      activity in the AD, CJD, or depression groups, but NEP-like activity and Abeta42
      levels correlated significantly in the FTD group. In AD and depression, the NEP
      like activity in CSF correlated with levels of p-tau, and, in the AD group, it
      also was correlated with t-tau levels. Our results suggest that the relation
      between the specific activity of NEP and t-tau and p-tau is a characteristic
      trait of AD. The correlation between NEP concentration and Abeta42 in FTD is
      unexpected and warrants further investigation. 

PMID- 23948878
TI  - Role of survivin as prognostic and clinicopathological marker in gastric cancer:
      a meta-analysis.
AB  - Survivin has been implicated as a potential prognostic marker in a wide range of
      malignant tumours. However, the prognostic impact of survivin in gastric cancer
      remains to be controversial and published data are sometimes heterogeneous. Thus,
      aim of this study was to review the literature by performing an electronical
      database search via PubMed and EMBASE to identify eligible studies that assessed
      the impact of survivin as prognostic marker and its association with
      clinicopathological variables. Database search until November 21st 2012 retrieved
      20 studies comprising 2,695 gastric cancer patients that assessed expression of
      survivin by immunohistochemistry or RT-PCR analyses in gastric cancer specimens.
      Meta-analyses of clinicopathological variables revealed an association between
      the expression of survivin and the presence of lymph node metastases (pooled OR:
      0.58; 95 % CI 0.35-0.96). In addition, a correlation between the expression of
      survivin and overall survival for patients with gastric cancer (pooled HR 1.93;
      95 % CI 1.51-2.48) became evident. More importantly, we were able to exclude a
      severe heterogeneity (I(2) = 31 %) or publication bias for the survival analyses.
      Furthermore, one-way sensitivity analysis and subgroup analyses regarding the
      method used to detect survivin, the type of survival analysis, the study quality
      and whether information was provided regarding neoadjuvant therapy supported our
      initial results. In conclusion, this meta-analysis indicates the prognostic
      significance of survivin in patients with gastric cancer. 

PMID- 23948880
TI  - Chronic intermittent hypoxia/reoxygenation facilitate amyloid-beta generation in
      mice.
AB  - Previous studies have shown a high prevalence of obstructive sleep apnea (OSA)
      among patients with Alzheimer's disease (AD). However, it is poorly assessed
      whether chronic intermittent hypoxia (CIH), which is a characteristic of OSA,
      affects the pathophysiology of AD. We aimed to investigate the direct effect of
      intermittent hypoxia (IH) in pathophysiology of AD in vivo and in vitro. In vivo,
      15 male triple transgenic AD mice were exposed to either CIH or normoxia (5% O2
      and 21% O2 every 10 min, 8 h/day for 4 weeks). Amyloid-beta (Abeta) profile,
      cognitive brain function, and brain pathology were evaluated. In vitro, human
      neuroblastoma SH-SY5Y cells stably expressing wild-type amyloid-beta protein
      precursor were exposed to either IH (8 cycles of 1% O2 for 10 min followed by 21%
      O2 for 20 min) or normoxia. The Abeta profile in the conditioned medium was
      analyzed. CIH significantly increased levels of Abeta42 but not Abeta40 in the
      brains of mice without the increase in hypoxia-inducible factor 1, alpha subunit
      (HIF-1alpha) expression. Furthermore, CIH significantly increased intracellular
      Abeta in the brain cortex. There were no significant changes in cognitive
      function. IH significantly increased levels of Abeta42 in the medium of SH-SY5Y
      cells without the increase in the HIF-1alpha expression. CIH directly and
      selectively increased levels of Abeta42 in the AD model. Our results suggest that
      OSA would aggravate AD. Early detection and intervention of OSA in AD may help to
      alleviate the progression of the disease. 

PMID- 23948881
TI  - APOE-dependent phenotypes in subjects with mild cognitive impairment converting
      to Alzheimer's disease.
AB  - BACKGROUND: The E4 isoform of the APOE genotype is the most significant genetic
      risk factor for sporadic Alzheimer's disease (AD) and has recently been found to
      modulate disease expression in patients with AD. OBJECTIVE: To investigate APOE
      dependent cognitive and structural phenotypes in subjects with mild cognitive
      impairment who converted to AD within the following three years. METHODS:
      Subjects converting to AD (n = 63) were compared to a control group with stable
      mild cognitive impairment (n = 131). Clinical, neuropsychological, and MRI data
      were obtained by the German Dementia Competence Network. Subgroups of converting
      and stable APOE E4 carriers and non-carriers were investigated longitudinally
      with MRI to examine structural correlates of conversion. Voxel-based morphometry
      was applied to investigate gray matter distribution. RESULTS: At baseline,
      executive performance correlated with global and bilateral prefrontal gray matter
      volume and predicted conversion only among non-carriers. Converting carriers and
      non-carriers presented distinct patterns of brain atrophy on longitudinal
      analysis, in line with a dissociation between more pronounced occipital atrophy
      in carriers and more frontoparietal volume loss in non-carriers at follow-up.
      CONCLUSIONS: The current findings suggest that in APOE E4 non-carriers with AD,
      executive dysfunction is closely linked to frontal gray matter atrophy and
      predictive of progression to dementia. The results are consistent with APOE
      genotype-dependent profiles of structural damage and cognitive decline in
      patients with imminent conversion to AD.

PMID- 23948882
TI  - Blast exposure causes early and persistent aberrant phospho- and cleaved-tau
      expression in a murine model of mild blast-induced traumatic brain injury.
AB  - Mild traumatic brain injury (mTBI) is considered the 'signature injury' of combat
      veterans that have served during the wars in Iraq and Afghanistan. This
      prevalence of mTBI is due in part to the common exposure to high explosive blasts
      in combat zones. In addition to the threats of blunt impact trauma caused by
      flying objects and the head itself being propelled against objects, the primary
      blast overpressure (BOP) generated by high explosives is capable of injuring the
      brain. Compared to other means of causing TBI, the pathophysiology of mild-to
      moderate BOP is less well understood. To study the consequences of BOP exposure
      in mice, we employed a well-established approach using a compressed gas-driven
      shock tube that recapitulates battlefield-relevant open-field BOP. We found that
      24 hours post-blast a single mild BOP provoked elevation of multiple phospho- and
      cleaved-tau species in neurons, as well as elevating manganese superoxide
      dismutase (MnSOD or SOD2) levels, a cellular response to oxidative stress. In
      hippocampus, aberrant tau species persisted for at least 30 days post-exposure,
      while SOD2 levels returned to sham control levels. These findings suggest that
      elevated phospho- and cleaved-tau species may be among the initiating pathologic
      processes induced by mild blast exposure. These findings may have important
      implications for efforts to prevent blast-induced insults to the brain from
      progressing into long-term neurodegenerative disease processes. 

PMID- 23948883
TI  - Angiotensin converting enzyme inhibitors and the reduced risk of Alzheimer's
      disease in the absence of apolipoprotein E4 allele.
AB  - Our cross-sectional study showed that the interaction between apolipoprotein E4
      (ApoE4) and angiotensin converting enzyme (ACE) inhibitors was associated with
      Alzheimer's disease (AD). The aim of this longitudinal study was to differentiate
      whether ACE inhibitors accelerate or reduce the risk of AD in the context of ApoE
      alleles. Using the longitudinal data from the National Alzheimer's Coordinating
      Center (NACC) with ApoE genotyping and documentation of ACE inhibitors use, we
      found that in the absence of ApoE4, subjects who had been taking central ACE
      inhibitor use (chi2 test: 21% versus 27%, p = 0.0002) or peripheral ACE inhibitor
      use (chi2 test: 13% versus 27%, p < 0.0001) had lower incidence of AD compared
      with those who had not been taking an ACE inhibitor. In contrast, in the presence
      of ApoE4, there was no such association between ACE inhibitor use and the risk of
      AD. After adjusting for the confounders, central ACE inhibitor use (OR = 0.68,
      95% CI = 0.55, 0.83, p = 0.0002) or peripheral ACE inhibitor use (OR = 0.33, 95%
      CI = 0.33, 0.68, p < 0.0001) still remained inversely associated with a risk of
      developing AD in ApoE4 non-carriers. In conclusion, ACE inhibitors, especially
      peripherally acting ones, were associated with a reduced risk of AD in the
      absence of ApoE4, but had no such effect in those carrying the ApoE4 allele. A
      double-blind clinical trial should be considered to determine the effect of ACE
      inhibitors on prevention of AD in the context of ApoE genotype. 

PMID- 23948884
TI  - Meta-analysis of memory and executive dysfunctions in relation to vitamin D.
AB  - BACKGROUND: Hypovitaminosis D is associated with global cognitive impairment in
      adults. It remains unclear which domain-specific cognitive functions are affected
      with hypovitaminosis D. OBJECTIVE: To systematically review and quantitatively
      synthesize the association of serum 25-hydroxyvitamin D (25OHD) concentrations
      with episodic memory and executive functions in adults. METHODS: A Medline and
      PsycINFO libraries search was conducted on May 2012, with no limit of date, using
      the Medical Subject Headings (MeSH) terms "Vitamin D" OR
      "Hydroxycholecalciferols" combined with the MeSH terms "Memory" OR "Memory
      Disorders" OR "Executive Function" OR "Attention" OR "Cognition" OR "Cognition
      disorders" OR "Dementia" OR "Alzheimer disease" OR "Neuropsychological Tests".
      Fixed-effects meta-analysis was performed from 12 eligible studies using an
      inverse-variance method. RESULTS: Of the 285 selected studies, 14 observational
      studies (including 3 prospective cohort studies) and 3 interventional studies met
      the selection criteria. All were of good quality. The number of participants
      ranged from 44-5,692 community-dwellers (0-100% women). In the pooled analysis,
      although episodic memory disorders showed only modest association with lower
      25OHD concentrations (summary effect size of the difference (ES) = -0.09 [95%CI:
      0.16;-0.03]), associations of greater magnitude were found with executive
      dysfunctions (processing speed: mean difference of Trail Making Test (TMT)-A
      score = 4.0 [95% CI:1.20;6.83]; mental shifting: mean difference of TMT-B score =
      12.47 [95% CI:6.78;18.16]; information updating tests: ES = -0.31 [95% CI:-0.5;
      0.09]). The pooled risk of incident decline of TMT-B score was OR = 1.25 [95%
      CI:1.05;1.48] in case of initial lower 25OHD concentrations. Vitamin D repletion
      resulted in improved executive functions (ES = -0.50 [95% CI:-0.69;-0.32] for
      before-and-after comparison), but exhibited no difference with control groups (ES
      = 0.14 [95% CI:-0.04;0.32] for between-group comparison after intervention).
      CONCLUSION: Lower serum 25OHD concentrations predict executive dysfunctions,
      especially on mental shifting, information updating and processing speed. The
      association with episodic memory remains uncertain.

PMID- 23948885
TI  - BDNF, TNFalpha, HSP90, CFH, and IL-10 serum levels in patients with early or late
      onset Alzheimer's disease or mild cognitive impairment.
AB  - Identifying early-detection biomarkers have become an increasingly important
      approach in the treatment and prevention of Alzheimer's disease (AD). In this
      study, we investigated the potential of brain-derived neurotrophic factor (BDNF),
      complement factor H (CFH), tumor necrosis factor-alpha (TNFalpha), interleukin 10
      (IL-10), and heat shock protein 90 (Hsp90) as serum biomarkers for AD in a cohort
      of the Turkish population because they have been suggested to be associated with
      AD. Serum BDNF, CFH, TNFalpha, IL-10, and Hsp90 levels in three groups of
      patients, early-onset AD (EOAD; age of onset < 65; n = 22), late-onset AD (LOAD;
      age of onset > 65; n = 54), and mild cognitive impairment (MCI) (n = 30), were
      compared with age-matched healthy controls (age < 65, n = 18 and age > 65; n =
      32) using ELISA. The serum BDNF levels significantly decreased and TNFalpha
      levels significantly increased in the EOAD and LOAD groups compared to the age
      matched healthy controls. There was a correlation between serum TNFalpha and IL
      10 levels in the LOAD and healthy control groups. Serum CFH levels in the LOAD
      and MCI patients were significantly decreased compared with controls. Serum Hsp90
      levels in the EOAD, LOAD, and MCI patients were significantly decreased compared
      with controls. The protein misfolding, the inflammatory response, and decreased
      neurotrophic factor synthesis are all suggested to be related to AD type brain
      pathology, and our results indicate these alterations might be traced from serum
      samples. For accurate early diagnosis of AD, it is important to determine a
      profile of alterations in multiple biomarkers in large-scale population studies. 

PMID- 23948886
TI  - Intronic rs2147363 variant in ATP7B transcription factor-binding site associated
      with Alzheimer's disease.
AB  - Copper homeostasis abnormalities have been shown to be associated with
      Alzheimer's disease (AD), possibly by accelerating amyloid-beta toxicity and
      plaque formation. The ATP7B gene plays a key role in controlling body copper
      balance. Our previous studies showed an association between ATP7B variants and AD
      risk. Among these variants, an intronic single nucleotide polymorphism,
      rs2147363, was associated with AD risk. In order to understand this intronic
      association, we screened a population of 286 AD patients and 283 healthy
      controls, and verified the presence of other functional coding variants in
      linkage disequilibrium (LD). Then we searched for a regulatory function region
      close to rs2147363. An LD analysis revealed the presence of an LD between
      rs2147363 and a Wilson's disease-causing variant, rs7334118. However, this
      mutation did not explain the observed genetic association. Conversely, in silico
      analyses of rs2147363 functionality highlighted that this variant is located in a
      binding site of a transcription factor, and is, consequently, associated with
      regulatory function. These data suggest that the genetic variation in cis
      regulatory elements located in non-coding regions can have a role in determining
      ATP7B functionality and account for some of the AD missing hereditability. 

PMID- 23948887
TI  - CaV1.2 calcium channel expression in reactive astrocytes is associated with the
      formation of amyloid-beta plaques in an Alzheimer's disease mouse model.
AB  - Increased activity of L-type Ca2+ channels has been implicated in the
      pathogenesis of dementia and Alzheimer's disease (AD). Previously we detected
      CaV1.2 alpha1-subunit-positive expression in reactive astrocytes surrounding the
      plaques of 12 month-old transgenic mice overexpressing hAbetaPP751 with the
      London (V717I) and Swedish (K670M/N671L) mutations. Here we examined whether
      increased CaV1.2 alpha1-subunit expression precedes plaque formation or is
      specifically associated with the increased amyloid-beta (Abeta) load in the
      plaques. Quantitative RT-PCR expression profiling of all high voltage-gated Ca2+
      channel subunits (alpha1, beta, and alpha2delta) revealed no difference in the
      hippocampi of 2, 4, and 11 month-old wild type (wt) and transgenic (tg) mice.
      Immunohistochemistry demonstrated that expression of CaV1.2 alpha1-subunit, but
      not of the auxiliary beta4 Ca2+ channel subunit, specifically associated with
      Abeta-positive plaques in brains of 11 month tg mice. No difference in CaV1.2
      alpha1-subunit labeling was found in 2 and 4 month-old wt and tg mice prior to
      plaque formation. The CaV1.2 alpha1-subunit-positive cells in 11 month-old tg
      mice also labeled with GFAP, but not with the microglia marker Iba1. In contrast,
      GFAP-positive cells induced by injection of quinolinic acid did not reveal any
      CaV1.2 alpha1-subunit immunoreactivity. Together these results indicate that the
      expression of CaV1.2 alpha1-subunits in reactive astrocytes in the tg AD mouse
      model is related to the increased amyloid-beta load in the plaques rather than
      caused by effects on gene regulation or mechanisms preceding the manifestation of
      AD as seen by plaque formation. 

PMID- 23948889
TI  - Upregulation and expression patterns of the angiogenic transcription factor ets-1
      in Alzheimer's disease brain.
AB  - Immunohistochemical staining has been used to determine expression patterns of
      the angiogenic transcription factor, Ets-1, in the brains of Alzheimer's disease
      (AD) individuals. Brain tissue from non-demented controls showed little
      expression of Ets-1 whereas in AD brain tissue, Ets-1 was ubiquitously expressed
      in cortex and hippocampus. Double immunostaining with von Willerbrand factor
      demonstrated prominent Ets-1 intravascular immunoreactivity (ir) in AD cortical
      microvessels. In addition, Ets-1 also exhibited extravascular expression
      characterized by a diffuse pattern of Ets-1 ir in AD brain. Double staining also
      showed Ets-1 colocalization in microvasculature with the potent angiogenic agent,
      vascular endothelial growth factor (VEGF). Cell-associated tumor necrosis factor
      alpha (TNF-alpha), a pro-inflammatory cytokine with pro-angiogenic activity, was
      primarily associated with diffuse extravascular Ets-1 ir. Clusters of HLA-DR
      positive microglia, resident immune cells of brain which release TNF-alpha, were
      also localized with diffuse Ets-1. Intravascular Ets-1 ir was maximally co
      localized with soluble amyloid-beta peptide (Abeta), Abeta1-40, in
      microvasculature whereas diffuse extravascular Ets-1 ir appeared in proximity to
      Abeta plaques in brain parenchyma. Similar overall results were obtained for
      patterns of Ets-1 staining in AD hippocampal tissue. This work provides novel
      findings on expression of the angiogenic transcription factor, Ets-1, in vascular
      remodeling and its association with pro-angiogenic factors, reactive microglia,
      and Abeta deposition in AD brain. 

PMID- 23948888
TI  - AbetaPP-selective BACE inhibitors (ASBI): novel class of therapeutic agents for
      alzheimer's disease.
AB  - A systematic approach was used to identify AbetaPP-selective BACE inhibitors
      (ASBI) and to evaluate their in vivo ability to modulate AbetaPP processing
      selectively. We identified a bioflavonoid nutritional supplement as a molecular
      lead that acts as an ASBI in cell models, and show that increasing brain levels
      of this bioflavonoid through a pro-drug approach leads to reduction of Abeta42 in
      an Alzheimer's disease mouse model. ASBIs represent a novel class of candidate
      therapeutic agents for Alzheimer's disease. 

PMID- 23948890
TI  - Subcutaneous administration of liraglutide ameliorates Alzheimer-associated tau
      hyperphosphorylation in rats with type 2 diabetes.
AB  - BACKGROUND/OBJECTIVE: Type 2 diabetes increases the risk for developing
      Alzheimer's disease (AD), a progressive neurodegenerative disorder. Brain insulin
      resistance contributes to the pathogenesis of AD, and abnormal
      hyperphosphorylation of tau protein is crucial to neurodegeneration. Here we
      studied whether liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) and a
      new anti-diabetic drug, can promote brain insulin signaling and inhibit tau
      hyperphosphorylation in the brains of type 2 diabetic rats. METHODS: Type 2
      diabetic rats were treated with subcutaneous administration of liraglutide (0.2
      mg/kg body weight) or, as a control, saline twice a day for up to four weeks.
      Blood, cerebrospinal fluid (CSF), and brain tissue (n = 7 each group) were
      collected for analyses after liraglutide or saline administration for one, two,
      three, and four weeks. RESULTS: We found decreased CSF insulin,
      hyperphosphorylation of tau at AD-relevant phosphorylation sites, and decreased
      phosphorylation of protein kinase B (AKT) and glycogen synthase kinase-3beta (GSK
      3beta) in the brain, which indicated decreased insulin signaling leading to
      overactivation of GSK-3beta, a major tau kinase, in type 2 diabetic rats.
      Liraglutide treatment not only ameliorated hyperglycemia and peripheral insulin
      resistance, but also reversed these brain abnormalities in a time-dependent
      manner. CONCLUSION: Our results indicated that subcutaneous administration of
      liraglutide restores both peripheral and brain insulin sensitivity and
      ameliorates tau hyperphosphorylation in rats with type 2 diabetes. These findings
      support the potential use of liraglutide for the prevention and treatment of AD
      in individuals with type 2 diabetes.

PMID- 23948891
TI  - How it all started: tau and protein phosphatase 2A.
AB  - This review is dedicated to Inge Grundke-Iqbal who laid the foundations of the
      tau field, by isolating tau from the Alzheimer's disease (AD) brain, discovering
      that tau is hyperphosphorylated, and proving a critical role of protein
      phosphatase 2A (PP2A) and its endogenous inhibitor I2PP2A in this process. This
      memorial starts with a few personal notes, and then covers how subcellular
      fractionation helped in isolating tau. We review in detail the role of PP2A and
      its endogenous inhibitor in tau phosphorylation. We discuss the role that
      methylation and phosphorylation have in regulating PP2A activity. We add what we
      have contributed to understanding the role of tau and PP2A in AD using PP2A
      transgenic and knockout models, and conclude by addressing two underexplored
      areas in tau research: tau's non-canonical functions and the role distinct tau
      isoforms have in a physiological context. 

PMID- 23948893
TI  - An updated meta-analysis of the association between SORL1 variants and the risk
      for sporadic Alzheimer's disease.
AB  - The pathogenetic mechanism of Alzheimer's disease (AD) is still unknown; however,
      genetic variants play a critical role in the pathogenesis of AD. It has been
      reported that single nucleotide polymorphisms (SNPs) of the sortilin-related
      receptor with A-type repeats (SORL1, also called LR11 or sorLA) are associated
      with late-onset AD in Caucasian populations. Subsequently, other researchers have
      attempted to validate this finding in different ethnic populations. However,
      these findings have produced both negative and positive results. To derive a more
      precise estimation of whether SORL1 variants are associated with sporadic AD
      (SAD), we performed the meta-analysis presented in this manuscript. Databases
      including PubMed, AlzGene, the China National Knowledge Infrastructure (CNKI),
      and Wan Fang were searched to find relevant studies. Odds ratios (ORs) with 95%
      confidence intervals (CIs) were used to assess the strength of the association
      studies. A total of twenty-three case-control studies involving 11,837 cases and
      20,022 controls were included. Among the eleven candidate SNPs highlighted in the
      previous study, four SNPs (SNP 4, SNP 5, SNP 8 and SNP 10) showed a significant
      association with SAD using a generalized odds ratio (ORG, a model-free approach)
      and linkage disequilibrium structure analysis. Meanwhile, no significant
      heterogeneity between the Caucasian and Asian populations for the associated SNPs
      was observed in the current meta-analysis. Moreover, we further confirmed that
      the SORL1 three-marker haplotype C-G-C at SNP 8-SNP 9-SNP 10 was significantly
      associated with SAD (OR = 1.37, 95% CI = 1.12-1.66, padj = 0.008). The current
      meta-analysis further supports the previous findings that the SORL1 gene may be
      associated with SAD risk. 

PMID- 23948892
TI  - Early intervention with an estrogen receptor beta-selective phytoestrogenic
      formulation prolongs survival, improves spatial recognition memory, and slows
      progression of amyloid pathology in a female mouse model of Alzheimer's disease.
AB  - Our recent developments have yielded a novel phytoestrogenic formulation,
      referred to as the phyto-beta-SERM formulation, which exhibits an 83-fold binding
      selectivity for the estrogen receptor subtype beta (ERbeta) over ERalpha. Earlier
      studies indicate that the phyto-beta-SERM formulation is neuroprotective and
      promotes estrogenic mechanisms in the brain while devoid of feminizing activity
      in the periphery. Further investigation in a mouse model of human menopause
      indicates that chronic exposure to the phyto-beta-SERM formulation at a
      clinically relevant dosage prevents/alleviates menopause-related climacteric
      symptoms. This study assessed the efficacy, in an early intervention paradigm, of
      the phyto-beta-SERM formulation in the regulation of early stages of physical and
      neurological changes associated with Alzheimer's disease (AD) in a female triple
      transgenic mouse model of AD. Results demonstrated that, when initiated prior to
      the appearance of AD pathology, a 9-month dietary supplementation with the phyto
      beta-SERM formulation promoted physical health, prolonged survival, improved
      spatial recognition memory, and attenuated amyloid-beta deposition and plaque
      formation in the brains of treated AD mice. In comparison, dietary
      supplementation of a commercial soy extract preparation showed no effect on
      cognitive measures, although it appeared to have a positive impact on amyloid
      pathology. In overall agreement with the behavioral and histological outcomes,
      results from a gene expression profiling analysis offered insights on the
      underlying molecular mechanisms associated with the two dietary treatments. In
      particular, the data suggests that there may be a crosstalk between ERbeta and
      glycogen synthase kinase 3 signaling pathways that could play a role in
      conferring ERbeta-mediated neuroprotection against AD. Taken together, these
      results support the therapeutic potential of the phyto-beta-SERM formulation for
      prevention and/or early intervention of AD, and warrants further investigations
      in human studies. 

PMID- 23948894
TI  - Natural progression model of cognition and physical functioning among people with
      mild cognitive impairment and alzheimer's disease.
AB  - BACKGROUND: Empirical models of the natural history of Alzheimer's disease (AD)
      may help to evaluate new interventions for AD. OBJECTIVE: We aimed to estimate AD
      free survival time in people with mild cognitive impairment (MCI) and decline of
      cognitive and physical function in AD cases. METHODS: Within the Kungsholmen
      project, 153 incident MCI and 323 incident AD cases (international criteria) were
      identified during 9 years of follow-up in a cognitively healthy cohort of elderly
      people aged >=75 at baseline (n = 1,082). Global cognitive function was assessed
      with the Mini-Mental State Examination (MMSE), and daily life function was
      evaluated with the Katz index of activities of daily living (ADL) at each follow
      up examination. Data were analyzed using parametric survival analysis and mixed
      effect models. RESULTS: Median AD-free survival time of 153 participants with
      incident MCI was 3.5 years. Among 323 incident AD cases, the cognitive decline
      was 1.84 MMSE points per year, which was significantly associated with age.
      Physical functioning declined by 0.38 ADL points per year and was significantly
      associated with age, education, and MMSE, but not with gender. CONCLUSION:
      Elderly people with MCI may develop AD in approximately 3.5 years. Both cognitive
      and physical function may decline gradually after AD onset. The empirical models
      can be used to evaluate long-term disease progression of new interventions for
      AD.

PMID- 23948895
TI  - Tauopathies and tau oligomers.
AB  - Tauopathies are neurodegenerative diseases characterized behaviorally by dementia
      and neuropathologically by neurofibrillary tangles and neuronal loss. Tau gene
      mutations have been found in frontotemporal dementia with parkinsonism linked to
      chromosome 17, suggesting that mutation of tau induces tauopathy. Studies on in
      vitro tau aggregation show that tau forms two different intermediate aggregates-
      called tau oligomers and granular tau oligomers--before forming fibrils.
      Moreover, studies using a mouse model that expresses human tau demonstrated that
      the process of neurofibrillary tangle formation, rather than tangles themselves,
      may cause synapse loss and neuron loss. Further analyses suggest that
      hyperphosphorylated tau or oligomeric tau is involved in synaptic loss, whereas
      granular tau oligomers are responsible for neuronal loss. Thus, different forms
      of tau aggregates are involved in the different pathological changes that occur
      in tauopathies.

PMID- 23948896
TI  - Microtubule depolymerization and tau phosphorylation.
AB  - Inge Grundke-Iqbal and Khalid Iqbal found a connection between microtubule
      associated tau and Alzheimer's disease. They described that abnormally
      phosphorylated tau is a component of the paired helical filaments found in the
      disease. Afterwards they described that tau hyperphosphorylation prevents
      microtubule assembly. Now trying to complement the relationship between
      microtubules and tau phosphorylation, we have commented on the effect of
      microtubule disassembly on tau phosphorylation. In this study, we investigated
      the role of microtubule depolymerization induced by nocodazole on tau
      phosphorylation in human neuroblastoma SH-SY5Y cells. Our results indicate that
      nocodazole provokes tau phosphorylation mediated by GSK3, as determined by using
      AT-8 or Tau-1 antibodies. Interestingly, total GSK3beta and GSK3beta
      phosphorylation on Ser-9 are not altered during nocodazole treatment. In
      addition, microtubule stabilization with taxol had similar effects, likely
      because taxol and tau compete for the same binding sites on microtubules, and in
      the presence of taxol, tau could be detached from microtubules. Thus, unbound tau
      from microtubles can be phosphorylated by GSK3, even if the activity of GSK3 is
      not altered, probably because tau unbound to microtubules could be a better
      substrate for the kinase than microtubule-associated tau. These findings suggest
      that microtubule depolymerization can be a primary event in neurodegenerative
      disorders like Alzheimer's disease and that tau phosphorylation takes place
      afterwards. 

PMID- 23948897
TI  - Lithium attenuates scopolamine-induced memory deficits with inhibition of GSK
      3beta and preservation of postsynaptic components.
AB  - Cholinergic dysfunction plays a crucial role in the memory deterioration of
      Alzheimer's disease, but the molecular mechanism is not fully understood. By
      employing a widely recognized cholinergic dysfunction rat model that was produced
      by intraperitoneal injection of scopolamine, we investigated the mechanisms
      underlying scopolamine-induced memory deficits. We found that scopolamine caused
      spatial learning and memory deficits that involved activation of glycogen
      synthase kinase-3beta (GSK-3beta) and impairments of dendrite arborization and
      spine formation/maturation associated with alterations of AMPAR, Homer1, and
      CREB. Pretreatment by intraperitoneal injection of lithium, an inhibitor of GSK
      3, for one week prevented the synaptic changes and the learning and memory
      deficits induced by scopolamine. Lithium treatment also activated
      cholineacetyltransferase and inhibited acetylcholinesterase, which might have
      also contributed to the improved memory. Our findings suggest that GSK-3beta may
      be a key molecular mediator of cholinergic synaptic dysfunction, and that
      inhibition of GSK-3beta by lithium may be promising in protecting cholinergic
      synaptic functions. 

PMID- 23948898
TI  - Role of ciliary neurotrophic factor in the proliferation and differentiation of
      neural stem cells.
AB  - Ciliary neurotrophic factor (CNTF) is a pleiotropic cytokine that has been fully
      studied for its structure, receptor, and signaling pathways and its multiplex
      effects on neural system, skeletal muscle, and weight control. Recent research
      demonstrates that CNTF also plays an important role in neurogenesis and the
      differentiation of neural stem cells. In this article, we summarize the general
      characteristics of CNTF and its function on neural stem cells, which could be a
      valuable therapeutic strategy in treating neurological disorders. 

PMID- 23948899
TI  - Presenilin-1 mutations in Alzheimer's disease: an update on genotype-phenotype
      relationships.
AB  - Presenilin 1 (PSEN1) gene mutations deterministic for Alzheimer's disease (AD)
      are associated with marked heterogeneity in clinical phenotype, with behavioral
      and psychiatric features, parkinsonism, myoclonus, epileptic seizures, spastic
      paraparesis, frontal behavioral changes suggestive of the phenotype of
      frontotemporal dementia, aphasia, and cerebellar ataxia being described as well
      as cognitive decline. This article reviews publications on the clinical
      neurological phenotype of PSEN1 mutations published between October 2008 and
      April 2013 and integrates this information with previous reviews to produce
      tabular summaries of phenotype and genotype. With the possible exception of
      "variant AD" (familial AD with spastic paraparesis), no clinical genotype
      phenotype correlations are obvious. The mechanisms underpinning the clinical
      heterogeneity associated with PSEN1 mutations remain unclear. The "presenilin
      hypothesis" posits a loss of essential presenilin protein functions as a
      consequence of gene mutation, which might be one factor influencing disease
      phenotype. 

PMID- 23948900
TI  - Global axonal transport rates are unaltered in htau mice in vivo.
AB  - Microtubule-based axonal transport is believed to become globally disrupted in
      Alzheimer's disease in part due to alterations of tau expression or
      phosphorylation. We previously showed that axonal transport rates along retinal
      ganglion axons are unaffected by deletion of normal mouse tau or by
      overexpression of wild-type human tau. Here, we report that htau mice expressing
      3-fold higher levels of human tau in the absence of mouse tau also display normal
      fast and slow transport kinetics despite the presence of abnormally
      hyperphosphorylated tau in some neurons. In addition, markers of slow transport
      (neurofilament light subunit) and fast transport (snap25) exhibit normal
      distributions along optic axons of these mice. These studies demonstrate that
      human tau overexpression, even when associated with a limited degree of tau
      pathology, does not necessarily impair general axonal transport function in vivo.

PMID- 23948901
TI  - Expression of Alzheimer-like pathological human tau induces a behavioral motor
      and olfactory learning deficit in Drosophila melanogaster.
AB  - A key characteristic of Alzheimer's disease and other tauopathies is the
      progressive accumulation of neurofibrillary tangles mainly composed of
      hyperphosphorylated tau protein. In the present study, we use transgenic
      Drosophila melanogaster as a model to analyze in vivo the effect of expressing
      pseudophosphorylated tau (S199E/T212E/T231E/S262E tau) on pathological human tau
      (PH-tau) and on the FTDP-17 mutant R406W (PH-tauR406W). We used two different
      inducers that produced different levels of tau expression. The expression of
      these forms of tau did not significantly affect the lifespan of the flies. Flies
      expressing PH-tau displayed a clear locomotor dysfunction compared to those
      expressing normal tau regardless of the level of expression. At lower level of
      expression, this pathological phenotype was found to be age-dependent. At 35 days
      old, PH-tau flies showed the strongest locomotor impairment compare to flies
      expressing human tau or control flies (46%, 18% and 18% of flies remained on the
      bottom of the vials, respectively). At higher levels of expression, PH-tau flies
      showed these defects at seven days of age and the dysfunction also became
      significant for flies expressing tauR406W and PH-tauR406W. Whole brain
      immunochemistry analysis revealed that PH-tau as well as PH-tauR406W appeared to
      have abnormal mushroom body structures, critical structures involved in olfactory
      learning and memory in Drosophila. Severe olfactory learning deficits were
      induced by the expression of PH-tau. Taken together, our findings demonstrate
      that PH-tau induced a toxic effect in Drosophila, as flies develop both an
      abnormal motor deficit, associated with disruption of the mushroom body neurons,
      and impaired olfactory learning. 

PMID- 23948902
TI  - Dysregulated mTOR-dependent signaling in neurodegeneration or carcinogenesis:
      implication for Alzheimer's disease and brain tumors.
AB  - Recent evidence implicated aberrant mammalian target of rapamycin (mTOR)
      dependent signaling in both Alzheimer's disease (AD) and brain tumors. This
      review focuses on the potential mechanisms shared by both neurodegeneration and
      carcinogenesis. In particular, attention was paid to the possible roles of mTOR
      dependent signaling in these two fundamental pathophysiological processes. We
      hypothesize that common stresses could lead either to progressive degeneration or
      uncontrolled carcinogenesis via cell type specific upregulation of mTOR-dependent
      signaling in the central nervous system while mTOR-mediated carcinogenesis might
      permit glial cells to escape from degeneration. 

PMID- 23948903
TI  - Animal models of the sporadic form of Alzheimer's disease: focus on the disease
      and not just the lesions.
AB  - Alzheimer's disease is multifactorial and involves several different mechanisms.
      The sporadic form of the disease accounts for over 99% of the cases. As of yet,
      there is no practical and widely available animal model of the sporadic form of
      the disease. In the Alzheimer's disease brain, the lysosomal enzyme asparaginyl
      endopeptidase is activated and translocated from the neuronal lysosomes to the
      cytoplasm, probably due to brain acidosis caused by ischemic changes associated
      with age-associated microinfarcts. The activated asparaginyl endopeptidase
      cleaves inhibitor-2 of protein phosphatase-2A, I2(PP2A), into I(2NTF) and I(2CTF)
      which translocate to the neuronal cytoplasm and inhibit the protein phosphatase
      activity and consequently the abnormal hyperphosphorylation of tau. Employing
      adeno-associated virus serotype 1 (AAV1) vector containing I(2NTF-CTF) and
      transduction of the brains of newborn rat pups with this virus, an animal model
      has been generated. The AAV1-I(2NTF-CTF) rats show neurodegeneration and
      cognitive impairment at 4 months and abnormal hyperphosphorylation and
      aggregation of tau and intraneuronal accumulation of amyloid-beta at 13 months.
      The AAV1-I(2NTF-CTF) rats not only offer a disease-relevant model of the sporadic
      form of Alzheimer's disease but also represent a practical and widely available
      animal model. This short perspective on the need to focus on and develop the
      disease-relevant models of the sporadic form of Alzheimer's disease very much
      reflects the thinking of Inge Grundke-Iqbal who passed away on September 22, 2012
      and to whom this article is dedicated.

PMID- 23948904
TI  - Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) enhances
      tau expression.
AB  - Microtubule-associated protein tau is found to be accumulated and aggregated in
      the brains of individuals with Alzheimer's disease and related tauopathies. Dual
      specificity tyrosine-phosphorylation regulated kinase 1A (Dyrk1A) is
      overexpressed in Down syndrome and may play a critical role in the early onset of
      tau pathology in this disease. To investigate the effect of Dyrk1A on tau
      expression, we co-expressed different isoforms of tau with Dyrk1A in HEK-293FT
      cells and measured the mRNA and protein levels of tau using RT-PCR and Western
      blots, respectively. We further investigated the mechanism of regulation of tau
      expression by Dyrk1A. We found that Dyrk1A enhanced tau expression in a dose
      dependent manner. The enhancement did not require the kinase activity of Dyrk1A.
      Dyrk1A increased the expression of tau isoforms containing exon 10 to a larger
      extent than isoforms lacking exon 10. The expression of endogenous tau in
      neuronal cells was also regulated by Dyrk1A, and increased tau levels were found
      in the brains of Ts65Dn mice that overexpress Dyrk1A due to partial trisomy of
      chromosome 16. Dyrk1A did not enhance tau gene transcription, but increased tau
      mRNA stability. These results suggest that Dyrk1A enhances tau expression by
      stabilizing its mRNA and provides a novel insight into the regulation of tau
      expression and a molecular mechanism of tauopathies. 

PMID- 23948906
TI  - Differences in the prevalence of dementia and mild cognitive impairment and
      cognitive functions between early and delayed responders in a community-based
      study of the elderly.
AB  - Significant differences exist in demographic characteristics between responders
      and non-responders in population-based studies on mental health and cognitive
      status, but much less is known regarding differences in the prevalence of
      dementia and cognitive dysfunction between them. Here we compared the prevalence
      of dementia and mild cognitive impairment between early responders of a mass
      brain function examination and delayed responders (non-responders of the mass
      brain function examination) in a survey of elderly Japanese citizens (>=65 years)
      to evaluate non-responder bias. All residents in an area of Nakajima, Japan, were
      considered as potential candidates (n = 783). Participants of a mass brain
      function examination were considered as "early responders." The cognitive
      functions of delayed responders were assessed by home visits. To assess the
      correlation between sociodemographic characteristics and cognitive functions, the
      early and delayed responders completed the same questionnaires and
      neuropsychological tests. Delayed responders (n = 320) were significantly older
      and less educated than the early responders (n = 307). The delayed responders
      also exhibited a higher frequency of dementia and mild cognitive impairment than
      the early responders, even when the groups were restricted to the age group 65-89
      years. Our results suggest that population-based studies likely underestimate the
      prevalence of dementia and mild cognitive impairment, especially if the
      participation rate is low. 

PMID- 23948905
TI  - Reduced VDAC1 protects against Alzheimer's disease, mitochondria, and synaptic
      deficiencies.
AB  - The objective of this study was to elucidate the effect of VDAC1 on Alzheimer's
      disease (AD)-related genes, mitochondrial activity, and synaptic viability.
      Recent knockout studies of VDAC1 revealed that homozygote VDAC1 knockout (VDAC1-/
      ) mice exhibited disrupted learning and synaptic plasticity, and in contrast,
      VDAC1+/- mice appeared normal in terms of lifespan, fertility, and viability
      relative to wild-type mice. However, the effects of reduced VDAC1 on
      mitochondrial/synaptic genes and mitochondrial function in AD-affected neurons
      are not well understood. In the present study, we characterized
      mitochondrial/synaptic and AD-related genes and mitochondrial function in VDAC1+/
      mice and VDAC1+/+ mice. We found reduced mRNA levels in the AD-related genes,
      including AbetaPP, Tau, PS1, PS2, and BACE1; increased levels of the
      mitochondrial fusion genes Mfn1, Mfn2; reduced levels of the fission genes Drp1
      and Fis1; and reduced levels of the mitochondrial permeability transition pore
      genes VDAC1, ANT, and CypD in VDAC1+/- mice relative to VDAC1+/+ mice. Hexokinase
      1 and 2 were significantly upregulated in the VDAC+/- mice. The synaptic genes
      synaptophysin, synapsin 1 and 2, synaptobrevin 1 and 2, neurogranin, and PSD95
      were also upregulated in the VDAC1+/- mice. Free radical production and lipid
      peroxidation levels were reduced in the VDAC1+/- mice, and cytochrome oxidase
      activity and ATP levels were elevated, indicating enhanced mitochondrial function
      in the VDAC1+/- mice. These findings suggest that reduced VDAC1 expression, such
      as that we found in the VDAC1+/- mice, may be beneficial to synaptic activity,
      may improve function, and may protect against toxicities of AD-related genes. 

PMID- 23948907
TI  - Distribution of SLC10A4, a synaptic vesicle protein in the human brain, and the
      association of this protein with Alzheimer's disease-related neuronal
      degeneration.
AB  - Member 4 of the sodium/bile acid co-transporter family of proteins (SLC10A4) was
      discovered as a synaptic vesicle protein. The distribution of Slc10a4 protein in
      the brain has only so far been assessed in adult rats. Here, we assessed the
      regional distribution of SLC10A4 in aged human brain by immunohistochemistry. The
      protein was ubiquitously expressed, particularly in the cholinergic and
      monoaminergic neurons and in the lateral geniculate body. The protein expression
      was not influenced by the postmortem delay or fixation time. Synaptic alterations
      are reported to be seen in Alzheimer's disease (AD) and the suggested function of
      SLC10A4 as a vesicular transporter for cholinergic neurotransmitters proposes a
      link between this protein and AD. With increased severity of AD-related
      pathology, depletion of SLC10A4 expression was noted in the transentorhinal
      cortex. Intriguingly, in the most severely affected cases (Braak V), two patterns
      were noted, i.e., those with severe depletion of SLC10A4 and those with numerous
      neurons displaying SLC10A4. In conclusion, assessment of the expression of
      SLC10A4 by means of immunohistochemistry is feasible. The observed depletion of
      SLC10A4 with increase in the severity of AD-related neuronal degeneration is
      interesting and the observation that some subjects in Braak V displayed none and
      some displayed numerous SLC10A4 immunoreactive neurons is intriguing. Assessment
      of the SLC10A4 protein in neurodegenerative diseases or diseases affecting
      lateral geniculate body should be carried out to investigate whether alterations
      in the expression of SLC10A4 in synaptic vesicles might be used as a marker of
      transmitter deficits (cholinergic, monoaminorgic) or other synaptic pathology. 

PMID- 23948908
TI  - Oxidative stress in CD90+ T-cells of AbetaPP/PS-1 transgenic mice.
AB  - Oxidative stress plays a role in Alzheimer's disease (AD) with elevated levels
      being present in tissues such as brain, plasma, and cerebrospinal fluid. The role
      of oxidative stress in the immune system of AD is less established. Therefore, we
      measured protein markers of oxidative stress--protein carbonyls (PCO) and 3
      nitrotyrosine (3NT)--in CD90+ T-cells of a double-transgenic AD mouse model.
      Higher levels of PCO and 3NT were detected in amyloid-beta protein
      precursor/presenilin-1 (AbetaPP/PS-1) mice and increased with disease
      progression. These studies provide evidence that oxidative stress in the immune
      system may be useful for understanding disease pathogenesis.

PMID- 23948909
TI  - Depression and Alzheimer's disease: novel postmortem brain studies reveal a
      possible common mechanism.
AB  - The relationship between depression and Alzheimer's disease (AD) has always been
      relevant and controversial. Here, we briefly review epidemiological and
      biological studies that have investigated these disorders and then introduce our
      recent research about postmortem brains from patients with major depressive
      disorder (MDD). Our novel methodological approaches have revealed that MDD may be
      associated with an unknown type of myelin/myelination abnormalities in the
      frontopolar cortex. Based mainly on our findings, as well as on neuropathological
      observations by Braak and Braak (Acta Neuropathol 9, 197-201, 1996), we discuss
      the possible existence of an as yet unknown common mechanism linking the
      pathophysiologies underlying both depression and AD. 

PMID- 23948910
TI  - Amyloid-beta deposition and olfactory dysfunction in an Alzheimer's disease
      model.
AB  - Olfactory dysfunction is closely related to Alzheimer's disease (AD). Yet the
      mechanism behind this dysfunction remains largely unknown. To clarify the
      relationship between olfactory and memory deficits, we assessed behavioral and
      olfactory system pathology in AbetaPP/PS1 transgenic mice using the olfactory
      threshold test, the Morris water maze, Western blotting, immunohistochemistry
      (IHC), and thioflavine-s staining. Western blotting revealed the following
      spatial-temporal deposition of amyloid-beta (Abeta): appeared in the olfactory
      epithelium at 1-2 months old (mo); expanded to the olfactory bulb at 3-4 mo;
      expanded to the anterior olfactory nucleus, piriform cortex, entorhinal cortex,
      and hippocampus at 6-7 mo; and increased with age (9-10 mo) in the more central
      cortices. IHC staining showed similar results, but the appearance time points for
      the spotty signals in these brain regions were earlier due to the higher spatial
      resolution compared with Western blotting. The spread of Abeta deposits from the
      olfactory epithelium to the olfactory bulb, the anterior olfactory nucleus, and
      piriform cotex (faint) at 3-4 mo correlated with the olfactory detection deficit
      found at the corresponding age; and the high level of depositions in the more
      central regions at 9-10 mo correlated with spatial memory deficit at the same
      age. We also found that a decline in the levels of olfactory marker protein, a
      marker of functioning olfactory sensory neuron, coincided with soluble Abeta
      aggregates from a very early age in the olfactory epithelium, indicating early
      olfactory sensory neuron degeneration in the AbetaPP/PS1 mouse as in AD patients.
      The current data suggest that the early deposition of soluble Abeta aggregates in
      the olfactory system and the early deficit in olfactory dysfunction have the
      potential to serve as molecular markers for the early diagnosis of AD. 

PMID- 23948911
TI  - Tetrahydrohyperforin induces mitochondrial dynamics and prevents mitochondrial
      Ca2+ overload after Abeta and Abeta-AChE complex challenge in rat hippocampal
      neurons.
AB  - St. John's wort has been the subject of studies focused on its therapeutic
      properties against several diseases, including Alzheimer's disease (AD). Amyloid
      beta-peptide (Abeta), a critical peptide in AD, has been linked to the
      mitochondrial dysfunction often observed in this disease. Despite many efforts to
      prevent Abeta levels from increasing in AD, less has been done regarding the
      mitochondrial component. Therefore, we studied the effects of
      tetrahydrohyperforin (THH) on mitochondrial dysfunction of hippocampal neurons,
      challenged with Abeta oligomers (Abetao) and Abetao-AChE complexes. We show that
      THH prevents mitochondrial calcium overload and induces the modulation of fusion
      fission events, arresting mitochondrial dysfunction. Moreover, our results
      suggest that the modulation of mitochondrial dynamics probably occurs through a
      peroxisome proliferator-activated receptor gamma co-activator 1alpha-mediated
      mechanism, inducing mitochondrial fusion-fission protein expression. Our results
      offer further explanation for the effects observed for THH and the beneficial
      effects of this ethno-botanical drug in AD. 

PMID- 23948912
TI  - Progressive age-related cognitive decline in tau mice.
AB  - Age-related cognitive decline and neurodegenerative diseases are a growing
      challenge for society. Accumulation of tau pathology has been proposed to
      partially contribute to these impairments. This study provides a behavioral
      characterization during aging of transgenic mice bearing tau mutations. THY-Tau22
      mice were evaluated at ages wherein tau neuropathology in this transgenic mouse
      model is low (3-4 months), moderate (6-7 months), or extensive (>9 months).
      Spatial memory was found to be impaired only after 9 months of age in THY-Tau22
      mice, whereas non-spatial memory was affected as early as 6 months, appearing to
      offer an opportunity for assessing potential therapeutic agents in attenuating or
      preventing tauopathies through modulation of tau kinetics. 

PMID- 23948913
TI  - Intracellular localization of amyloid-beta peptide in SH-SY5Y neuroblastoma
      cells.
AB  - Amyloid-beta peptide (Abeta), the main component of Alzheimer's disease (AD)
      senile plaques, has been found to accumulate within the lysosomal compartment of
      AD neurons. We have previously shown that in differentiated SH-SY5Y neuroblastoma
      cells cultured under normal conditions, the majority of Abeta is localized
      extralysosomally, while oxidative stress significantly increases intralysosomal
      Abeta content through activation of macroautophagy. It is, however, not clear
      which cellular compartments contain extralysosomal Abeta in intact SH-SY5Y cells,
      and how oxidative stress influences the distribution of extralysosomal Abeta.
      Using confocal laser scanning microscopy and immunoelectron microscopy, we showed
      that in differentiated neuroblastoma cells cultured under normal conditions Abeta
      (Abeta40, Abeta42, and Abeta oligomers) is colocalized with both membrane-bound
      organelles (endoplasmic reticulum, Golgi complexes, multivesicular bodies/late
      endosomes, lysosomes, exocytotic vesicles and mitochondria) and non-membrane
      bound cytosolic structures. Neuroblastoma cells stably transfected with AbetaPP
      Swedish KM670/671NL double mutation showed enlarged amount of Abeta colocalized
      with membrane compartments. Suppression of exocytosis by 5 nM tetanus toxin
      resulted in a significant increase of the amount of cytosolic Abeta as well as
      Abeta colocalized with exocytotic vesicles, endoplasmic reticulum, Golgi
      complexes, and lysosomes. Hyperoxia increased Abeta localization in the
      endoplasmic reticulum, Golgi apparatus, mitochondria, and lysosomes, but not in
      the secretory vesicles. These results indicate that in SH-SY5Y neuroblastoma
      cells intracellular Abeta is not preferentially localized to any particular
      organelle and, to a large extent, is secreted from the cells. Challenging cells
      to hyperoxia, exocytosis inhibition, or Abeta overproduction increased
      intracellular Abeta levels but did not dramatically changed its localization
      pattern. 

PMID- 23948914
TI  - Maternal breastfeeding history and Alzheimer's disease risk.
AB  - The effect of early and midlife factors on later-life cognitive function has
      attracted scientific and public interest in recent years, especially with respect
      to hormonal risk factors for dementia. There is substantial evidence for
      reproductive history affecting Alzheimer's disease (AD) etiology. Here, we
      demonstrate how breastfeeding history affects women's risk of AD. Reproductive
      history data was collected, and AD diagnostic interviews were performed, for a
      cohort of elderly British women. Using Cox proportional-hazard models, we find
      that longer breastfeeding duration corresponded to reduced risk of AD (p < 0.01,
      n = 81). Women who breastfed had lower AD risk than women who did not breastfeed
      (p = 0.017, n = 81). Breastfeeding practices are an important modifier of
      cumulative endogenous hormone exposure for mothers. Ovarian hormone deprivation
      and/or insulin sensitivity benefits of breastfeeding may be responsible for the
      observed reduction in AD risk. Future studies concerning hormone effects on AD
      risk should consider how reproductive history leads to variation in endogenous
      hormone exposure and how this may influence the relationship between hormones and
      AD. 

PMID- 23948915
TI  - Phosphorylation of tau by death-associated protein kinase 1 antagonizes the
      kinase-induced cell apoptosis.
AB  - The intracellular accumulation of hyperphosphorylated tau plays a crucial role in
      neurodegeneration of Alzheimer's disease (AD), but the mechanism is not fully
      understood. From the observation that tau hyperphosphorylation renders cells more
      resistant to chemically-induced cell apoptosis, we have proposed that tau
      involved apoptotic abortion may be the trigger of neurodegeneration. Here, we
      further studied whether this phenomenon is also applicable for the cell death
      induced by constitutively expressed factors, such as death-associated protein
      kinase 1 (DAPK1). We found that DAPK1 was upregulated and accumulated in the
      brain of human tau transgenic mice. Overexpression of DAPK1 in HEK293 and N2a
      cells decreased cell viability with activation of caspase-3, whereas simultaneous
      expression of tau antagonized DAPK1-induced apoptotic cell death. Expression of
      DAPK1 induced tau hyperphosphorylation at Thr231, Ser262, and Ser396 with no
      effects on protein phosphatase 2A, glycogen synthase kinase-3beta, protein kinase
      A, calcium/calmodulin dependent protein kinase II, cell division cycle 2, or
      cyclin dependent protein kinase 5. The phosphorylation level of microtubule
      affinity-regulating kinase 2 (MARK2) was increased by expression of DAPK1, but
      simultaneous downregulation of MARK2 did not affect the DAPK1-induced tau
      hyperphosphorylation. DAPK1 was co-immunoprecipitated with tau proteins both in
      vivo and in vitro, and expression of the kinase domain-truncated DAPK1 did not
      induce tau hyperphosphorylation. These data suggest that tau hyperphosphorylation
      at Thr231, Ser262, and Ser396 by DAPK1 renders the cells more resistant to the
      kinase-induced apoptotic cell death, providing new insights into the tau-involved
      apoptotic abortion in the course of chronic neurodegeneration. 

PMID- 23948916
TI  - A new sandwich immunoassay for detection of the alpha-secretase cleaved, soluble
      amyloid-beta protein precursor in cerebrospinal fluid and serum.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder.
      Frequently used diagnostic biomarkers are amyloid-beta42 (Abeta42), tau, and
      phospho-tau, which are measured in cerebrospinal fluid (CSF), and allow a
      reasonable, but not full, separation of AD patients and controls. Besides
      Abeta42, additional proteolytic cleavage products of the amyloid-beta protein
      precursor (AbetaPP) have been investigated as potential biomarkers. This includes
      the alpha-secretase cleaved soluble AbetaPP ectodomain (sAbetaPPalpha). However,
      some studies found a reduction of sAbetaPPalpha, whereas other studies reported
      an increase of sAbetaPPalpha in the CSF of AD patients. The divergent findings
      may result from the detection of sAbetaPPalpha with antibodies, such as 6E10,
      which do not exclusively detect sAbetaPPalpha, but also the alternative beta
      secretase cleavage product sAbetaPPbeta'. Here, we used the sAbetaPPalpha
      specific antibody 14D6 and developed an ELISA-like sandwich immunoassay. The
      assay specifically detected sAbetaPPalpha in cell culture supernatants, in human
      CSF and even in serum, which is more readily accessible than CSF. The assay was
      used to analyze sAbetaPPalpha levels in CSF and serum of AD patients and
      controls. The assay detected a mild, but significant increase in sAbetaPPalpha in
      the CSF of AD patients compared to non-demented controls, while a mild reduction
      was observed in serum. The 14D6 assay in CSF allowed a better separation of AD
      patients from controls compared to the 6E10 antibody. Taken together, the new
      assay is widely applicable for specific sAbetaPPalpha measurement in culture
      media, CSF, and serum. 

PMID- 23948917
TI  - The selective BACE1 inhibitor VIa reduces amyloid-beta production in cell and
      mouse models of Alzheimer's disease.
AB  - beta-site amyloid-beta protein precursor cleaving enzyme 1 (BACE1) is the first
      protease and the rate limiting enzyme in the genesis of amyloid-beta (Abeta).
      This protein remains an important potential disease-modifying target for the
      development of drugs to treat Alzheimer's disease (AD). We are pursuing potent
      BACE1 inhibitors in an effort to identify suitable AD drug candidates. Our
      results have shown that the novel compound VIa exhibits potent inhibitory effects
      with IC50 = 5.9 nM and displays 30.8-fold, 7500-fold and 17533-fold selectivity
      against the other aspartic proteases BACE2, cathepsin D and renin, respectively.
      In cellular assays, VIa moderately reduces Abeta production: Abeta(1-40) with an
      IC50 = 143 nM and 1 nM VIa reduced Abeta(1-42) by 40.17%. Concomitant with VIa
      inhibiting the beta-cleavage of amyloid-beta protein precursor (AbetaPP), VIa
      increases the production of sAbetaPPalpha with an approximate EC50 of 16.5 nM. In
      testing this compound's efficacy in vivo, the oral administration of VIa resulted
      in a significant decrease in Abeta(1-40) and Abeta(1-42) in the blood of a mouse
      model of AD by 17.5-72.44% and 14.5-80.32%, respectively. This indicates that the
      novel compound VIa is a small, potent, selective, and non-peptidic BACE1
      inhibitor.

PMID- 23948918
TI  - Characterization of mitochondrial dysfunction in the 7PA2 cell model of
      Alzheimer's disease.
AB  - The 7WD4 and 7PA2 cell lines, widely used as cellular models for Alzheimer's
      disease (AD), have been used to investigate the effects of amyloid-beta protein
      precursor overexpression and amyloid-beta (Abeta) oligomer accumulation on
      mitochondrial function. Under standard culture conditions, both cell lines,
      compared to Chinese hamster ovary (CHO) control cells, displayed an ~5% decrease
      of O2 respiration as sustained by endogenous substrates. Functional impairment of
      the respiratory chain was found distributed among the protein complexes, though
      more evident at the level of complex I and complex IV. Measurements of ATP showed
      that its synthesis by oxidative phosphorylation is decreased in 7WD4 and 7PA2
      cells by ~25%, this loss being partly compensated by glycolysis (Warburg effect).
      Compensation proved to be more efficient in 7WD4 than in 7PA2 cells, the latter
      cell line displaying the highest reactive oxygen species production. The
      strongest deficit was observed in mitochondrial membrane potential that is almost
      40% and 60% lower in 7WD4 and 7PA2 cells, respectively, in comparison to CHO
      controls. All functional parameters point to a severe bioenergetic impairment of
      the AD cells, with the extent of mitochondrial dysfunction being correlated to
      the accumulation of Abeta peptides and oligomers. 

PMID- 23948919
TI  - Juvenile frontotemporal dementia with parkinsonism associated with tau mutation
      G389R.
AB  - Frontotemporal lobe degeneration includes a large spectrum of neurodegenerative
      disorders. Patients with frontotemporal dementia with parkinsonism linked to
      chromosome 17 exhibit heterogeneity in both clinical and neuropathological
      features. Here, we report the case of a young patient with a G389R mutation. This
      teenager girl was 17 years old when she progressively developed severe behavioral
      disturbances. First, she was considered to be suffering from atypical depression.
      After 2 years, she was referred to the department of neurology. By this time, the
      patient exhibited typical frontotemporal dementia with mild extrapyramidal
      disorders. The main behavioral features included apathy and reduced speech
      output. MRI and SPECT showed a frontotemporal atrophy and hypofixation,
      respectively. She died 7 years after onset. Three relatives on her father side
      had also died after early onset dementia. Genetic testing revealed a heterozygous
      guanine to cytosine mutation at the first base of codon 389 (Exon 13) of MAPT,
      the tau gene, resulting in a glycine to arginine substitution, in the patient and
      her non-affected father. Postmortem neuropathological and biochemical data
      indicate a Pick-like tau pathology but with phosphoserine 262-positive
      immunoreactivity. This case is remarkable because of the extremely early onset of
      the disease. 

PMID- 23948920
TI  - Amyloid-related imaging abnormalities in AbetaPP duplication carriers.
AB  - Immune response to vascular amyloid-beta deposits leads to cerebral amyloid
      angiopathy related-inflammation (CAA-ri). Amyloid-related imaging abnormalities
      (ARIA) were initially reported during anti-amyloid trials and are associated with
      the APOE 4/4 genotype. We report the evolution of an AbetaPP duplication carrier
      with an APOE 3/3 genotype presenting ARIA-Effusion and then ARIA-Hemosiderin
      deposit, without anti-amyloid therapy, suggestive of a possible spontaneously
      resolutive CAA-ri (not neuropathologically proven). It suggests common mechanisms
      between ARIA and CAA-ri and raises questions about mechanisms of this acute
      episode without APOE risk factor. The high vascular amyloid burden, induced by
      AbetaPP duplication, might increase amyloid epitope presentation and lead to
      inflammatory process. 

PMID- 23948921
TI  - Augmentation of sensory-evoked hemodynamic response in an early Alzheimer's
      disease mouse model.
AB  - Based on enlarged blood oxygen level-dependent (BOLD) responses in cognitively
      normal subjects at risk for Alzheimer's disease (AD), compensatory neuronal
      hyperactivation has been proposed as an early marker for diagnosis of AD. The
      BOLD response results from neurovascular coupling, i.e., hemodynamic response
      induced by neuronal activity. However, there has been no evidence of task-induced
      increases in hemodynamic response in animal models of AD. Here, we observed an
      augmented hemodynamic response pattern in a transgenic AbetaPP(SWE)/PS1DeltaE9
      mouse model of AD using three in vivo imaging methods: intrinsic optical signal
      imaging, multi-photon laser scanning microscopy, and laser Doppler flowmetry.
      Sensory stimulation resulted in augmented and prolonged hemodynamic responses in
      transgenic mice evidenced by changes in total, oxygenated, and deoxygenated
      hemoglobin concentration. This difference between transgenic and wild-type mice
      was significant at 7 months of age when amyloid plaques and cerebral amyloid
      angiopathy had developed but not at younger or older ages. Correspondingly,
      sensory stimulation-induced pial arteriole diameter was also augmented and
      prolonged in transgenic mice at 7 months of age. Cerebral blood flow response in
      transgenic mice was augmented but not prolonged. These results are consistent
      with the existence of BOLD signal hyperactivation in non-demented AD-risk human
      subjects, supporting its potential use as an early diagnostic marker of AD.

PMID- 23948923
TI  - Reduced visual event-related delta oscillatory responses in amnestic mild
      cognitive impairment.
AB  - Mild cognitive impairment (MCI) is considered as a prodromal stage for
      Alzheimer's disease (AD) in the majority of cases. Event-related oscillations
      might be used for detection of cognitive deficits. Our group's earlier results
      showed diminished delta visual and auditory target oscillatory responses in AD,
      and we investigated whether this prevails for MCI. Eighteen MCI subjects and 18
      age-matched healthy elderly controls were investigated. The maximum peak-to-peak
      amplitudes of oscillatory responses for each subject's averaged oscillatory
      target responses in delta, theta, and alpha frequency bands upon application of
      visual oddball paradigm were measured. Repeated measures of ANOVA was used to
      analyze four locations (frontal, central, parietal, occipital), at three coronal
      (left, midline, right) sites. Independent t tests were applied for post-hoc
      analyses. The oddball target delta response (0.5-3.0 Hz) was 26-32% lower in MCI
      than healthy controls over fronto-central-parietal regions [F(1.34) = 4.562, p =
      0.04]. Without a group effect, theta oscillatory responses (4-7 Hz) showed
      significant differences in coronal electrodes indicating highest values over mid
      electrode sites, and a anteriorposterior x coronal effect, being maximum at mid
      central. Alpha frequency band analyses indicated no statistical differences. Peak
      to-peak amplitudes of visual target delta oscillatory responses were lower in
      fronto-central-parietal regions in MCI than in healthy controls. This supports
      our earlier findings in AD, showing hypoactive delta fronto-central-parietal
      regions during cognitive tasks. These results indicate that event-related
      oscillations may detect early changes of brain dynamics in MCI, and deserves to
      be investigated as a candidate biomarker in further studies using multimodal
      techniques. 

PMID- 23948922
TI  - Increased susceptibility to amyloid-beta toxicity in rat brain microvascular
      endothelial cells under hyperglycemic conditions.
AB  - We hypothesized that hyperglycemia-induced mitochondrial dysfunction and
      oxidative stress are closely associated with amyloid-beta peptide (Abeta)
      toxicity in endothelial cells. Brain microvascular endothelial cells from rat
      (RBMEC) and mice (MBMEC) were isolated from adult Sprague-Dawley rats and
      homozygous db/db (Leprdb/Leprdb) and heterozygous (Dock7m/Leprdb) mice, and
      cultured under normo- and hyperglycemic conditions for 7 d followed by 24 h
      exposure to Abeta1-40. Some experiments were also performed with two
      mitochondrial superoxide (O2*-) scavengers, MitoTempo and Peg-SOD. Cell viability
      was measured by the Alamar blue assay and mitochondrial membrane potential
      (DeltaPsim) by confocal microscopy. Mitochondrial O2*- and hydrogen peroxide
      (H2O2) production was assessed by fluorescence microscopy and H2O2 production was
      confirmed by microplate reader. Hyperglycemia or Abeta1-40 alone did not affect
      cell viability in RBMEC. However, the simultaneous presence of high glucose and
      Abeta1-40 reduced cell viability and DeltaPsim, and enhanced mitochondrial O2*-
      and H2O2 production. MitoTempo and PEG-SOD prevented Abeta1-40 toxicity.
      Interestingly, MBMEC presented a similar pattern of alterations with db/db
      cultures presenting higher susceptibility to Abeta1-40. Overall, our results show
      that high glucose levels increase the susceptibility of brain microvascular
      endothelial cells to Abeta toxicity supporting the idea that hyperglycemia is a
      major risk factor for vascular injury associated with AD. 

PMID- 23948924
TI  - Evidence for the efficacy of latrepirdine (Dimebon) treatment for improvement of
      cognitive function: a meta-analysis.
AB  - Over the last few years, latrepirdine, a demode antihistamine drug, has been
      proposed to be useful for treating neurodegenerative disorders such as
      Alzheimer's and Huntington's diseases, and more recently schizophrenia. The
      mechanisms and pharmacological targets that are responsible for the beneficial
      effects on neurodegenerative diseases remain unknown. But it has been proposed
      that latrepirdine may modulate several targets including voltage-gate Ca+2
      channels, mitochondrial permeability pore transition, or several neurotransmitter
      receptors. Herein, we present a meta-analysis of randomized controlled trials to
      ascertain the efficacy and safety of latrepirdine on cognitive function. By doing
      a search in electronic databases, we found five clinical trials in which the
      effect of latrepirdine on cognition function has been studied, and this was
      evaluated using MMSE, ADAS-cog, ADCS-ADL, and NPI scores. Latrepirdine generally
      presented a good safety profile; it was well tolerated when given alone or in
      combination with a variety of other drugs. We observed heterogeneous results
      between trials; latrepirdine failed to exert a significant beneficial effect
      although it tended to improve cognitive scores. The only significant benefit that
      we found was for the NPI score in Alzheimer's disease patients. 

PMID- 23948925
TI  - Comparison of two different methods for measurement of amyloid-beta peptides in
      cerebrospinal fluid after BACE1 inhibition in a dog model.
AB  - Beta-secretase is the first cleavage enzyme of amyloid-beta protein precursor
      (AbetaPP) in the amyloidogenic pathway, leading to the formation of the plaque
      forming Amyloid-beta (Abeta)1-42 peptide. BACE (beta-site AbetaPP cleaving
      enzyme) 1 inhibition is therefore considered to be a promising disease modifying
      therapy for Alzheimer's disease. An early assessment of the in vivo activity of
      BACE inhibitors was done in dogs since AbetaPP processing is the same as in
      humans and this species easily enables longitudinal cerebrospinal fluid (CSF)
      sampling. Abeta changes in CSF compared to baseline are used to evaluate target
      engagement of the compounds. Levels of Abeta1-37, Abeta1-38, Abeta1-40, and
      Abeta1-42 in CSF are measured with immunoassay (Mesoscale
      electrochemiluminescence technology) and with an ultra high-performance liquid
      chromatography mass spectrometry (UPLC-MS/MS). Two experimental BACE inhibitors
      were evaluated. With the immunoassay, a dose dependent decrease is observed for
      all four Abeta peptides. Measurements with the UPLC-MS/MS are in line with the
      immunoassay for Abeta1-37, Abeta1-38, and Abeta1-40, however, for Abeta1-42,
      differences are sometimes observed when comparing to changes seen in the other
      peptides with UPLC-MS/MS and with immunoassay results. Generally lower
      concentrations are measured with immunoassay. The reason for these differences is
      still unknown. Abeta1-42 is more prone to form aggregates compared to the other
      peptides. One hypothesis could be that while the immunoassay only measures free
      Abeta, bound and aggregated Abeta peptides are at least partially dissolved with
      the UPLC-MS/MS method, since acetonitrile is added to the CSF samples. This
      increases variability in the concentration of Abeta peptide measured with UPLC
      MS/MS, especially for Abeta1-42, potentially masking the compound effect on
      Abeta1-42 levels. 

PMID- 23948926
TI  - Cognitive impairment in neurological diseases: lessons from apolipoprotein E.
AB  - Apolipoprotein E4 (ApoE4) has been considered to have detrimental effects on the
      age of onset and progression in Alzheimer's disease. Evidence continues to
      accumulate regarding the effects of ApoE isoforms in a number of other
      neurological diseases. Recent studies demonstrate an increase in cognitive
      deficits in ApoE4 patients with traumatic brain injury, cerebrovascular disease,
      and delirium. Evidence of the role ApoE isoforms played in cognition in multiple
      sclerosis has illuminated the neurodegenerative aspects of this disease. It
      further provides evidence of the effect neuroinflammation has in increasing
      susceptibility to cognitive decline in younger patients. Determining where these
      diverse diseases intersect and diverge in their relationship to ApoE provides
      insight into the two-hit mechanism in cognitive decline. 

PMID- 23948927
TI  - Serum amyloid a differentially activates microglia and astrocytes via the PI3K
      pathway.
AB  - Microglia and astrocytes in the brain play an important role in the development
      and progression of Alzheimer's disease (AD). Serum amyloid A (SAA) is a major
      acute-phase protein produced locally in the brain and colocalizes with senile
      plaques in AD patients. We investigated whether SAA plays a role in the
      development of AD. The viability of cultured primary microglia and astrocytes was
      measured by MTT; cell cycle and apoptosis analysis was also conducted. Cultured
      microglia and astrocytes were stimulated with 1 MUM SAA for different periods of
      time (2, 4, 6, 12 h) or treated with 1 MUM SAA with or without 15 min
      pretreatment of MAPK or PI3K inhibitors. Total RNA was extracted for qPCR
      analysis. SAA induced morphological changes of primary microglia but not
      astrocytes. Interestingly, SAA increased the viability of microglia by inhibiting
      their apoptosis and reduced the viability of astrocytes by inducing G1 cell cycle
      arresting. SAA treatment increased the mRNA levels of IL-6, TNF-alpha, IL12p40,
      IL23p19, and IL-10, with higher potency in microglia than in astrocytes. However,
      SAA induced more iNOS mRNA in astrocytes than in microglia. SAA induced these
      cytokines and iNOS expression by activating the PI3K pathway in both glial cells,
      but selectively activated the JNK pathway in microglia and the NF-kappaB pathway
      in astrocytes. These results suggest that SAA can stimulate a different reactive
      phenotype in microglia and astrocytes, and SAA regulates cell viability
      differently in these two glial cells in part through the PI3K pathway. 

PMID- 23948928
TI  - Using cerebrospinal fluid marker profiles in clinical diagnosis of dementia with
      Lewy bodies, Parkinson's disease, and Alzheimer's disease.
AB  - BACKGROUND: Dementia with Lewy bodies (DLB) is difficult to differentiate from
      other neuro-degenerative diseases. Patients are often mistaken to suffer from
      Parkinson's disease (PD) or Alzheimer's disease (AD) because of the overlapping
      clinical appearances concerning cognition and movement. OBJECTIVE: We
      investigated the possibility for a valid differential diagnosis using
      cerebrospinal fluid (CSF) biomarkers. METHODS: In the context of a large
      retrospective study, we analyzed data of patients suffering from degenerative,
      ischemic, or inflammatory CNS (central nervous system) diseases and identified
      those with DLB (n = 34), PD (n = 37), and AD (n = 47) for further analyses.
      RESULTS: We detected abnormalities in the CSF profiles of those patients with DLB
      while using a combination of decreased amyloid-beta (Abeta)42 and increased tau
      levels. By stratification of data by disease severity, we observed a high
      sensitivity of this combination especially in the subgroup of patients with
      advanced stages, while the sensitivity in early forms was lower. In addition,
      with clinical deterioration, the abnormalities in the CSF profile became more
      pronounced. CONCLUSION: We conclude that DLB can be distinguished from PD, in
      spite of both being synucleinopathies, by CSF profiles using neurodegenerative
      marker analysis. The pathophysiology of increased tau and decreased Abeta levels
      in those conditions has to be elucidated further, since both proteins are known
      to be involved in the pathogenesis of AD, but no clear explanation has been
      postulated for DLB yet.

PMID- 23948931
TI  - Tau oligomers and fibrils induce activation of microglial cells.
AB  - Neuroinflammation is a process related to the onset of several neurodegenerative
      disorders, including Alzheimer's disease (AD). Increasing sets of evidence
      support the major role of deregulation of the interaction patterns between glial
      cells and neurons in the pathway toward neuronal degeneration, a process we are
      calling neuroimmunomodulation in AD. On the basis of the hypothesis that
      pathological tau aggregates induce microglial activation with the subsequent
      events of the neuroinflammatory cascade, we have studied the effects of tau
      oligomeric species and filamentous structures over microglial cells in vitro. Tau
      oligomers and fibrils were induced by arachidonic acid and then their actions
      assayed upon addition to microglial cells. We showed activation of the microglia,
      with significant morphological alterations as analyzed by immunofluorescence. The
      augmentation of nitrites and the proinflammatory cytokine IL-6 was evaluated in
      ELISA assays. Furthermore, conditioned media of stimulated microglia cells were
      exposed to hippocampal neurons generating altered patterns in these cells,
      including shortening of neuritic processes and cytoskeleton reorganization. 

PMID- 23948932
TI  - Hippocampal neurogenesis in Alzheimer's disease: is there a role for dietary
      modulation?
AB  - Alterations in hippocampal neurogenesis have been recognized as an integral part
      of Alzheimer's disease. Adult hippocampal neurogenesis is regulated by intrinsic
      and extrinsic factors; one of them is diet. This review provides an assessment of
      the current state of the field in hippocampal neurogenesis studies in Alzheimer's
      disease and focuses on the role of diet. The review highlights some of the key
      dietary compounds and interventions such as calorie restriction, fat,
      polyphenols, zinc, folate, alcohol and thiamine, and emphasizes the pathways that
      they modify. 

PMID- 23948929
TI  - Picomolar amyloid-beta peptides enhance spontaneous astrocyte calcium transients.
AB  - Amyloid-beta (Abeta) peptides are constitutively produced in the brain throughout
      life via mechanisms that can be regulated by synaptic activity. Although Abeta
      has been extensively studied as the pathological plaque-forming protein species
      in Alzheimer's disease (AD), little is known about the normal physiological
      function(s) and signaling pathway(s). We previously discovered that
      physiologically-relevant, low picomolar amounts of Abeta can enhance synaptic
      plasticity and hippocampal-dependent cognition in mice. In this study, we
      demonstrated that astrocytes are cellular candidates for participating in this
      type of Abeta signaling. Using calcium imaging of primary astrocyte cultures, we
      observed that picomolar amounts of Abeta peptides can enhance spontaneous
      intracellular calcium transient signaling. After application of 200 pM Abeta42
      peptides, the frequency and amplitude averages of spontaneous cytosolic calcium
      transients were significantly increased. These effects were dependent on alpha7
      nicotinic acetylcholine receptors (alpha7-nAChRs), as the enhancement effects
      were blocked by a pharmacological alpha7-nAChR inhibitor and in astrocytes from
      an alpha7 deficient mouse strain. We additionally examined evoked intercellular
      calcium wave signaling but did not detect significant picomolar Abeta-induced
      alterations in propagation parameters. Overall, these results indicate that at a
      physiologically-relevant low picomolar concentration, Abeta peptides can enhance
      spontaneous astrocyte calcium transient signaling via alpha7-nAChRs. Since
      astrocyte-mediated gliotransmission has been previously found to have
      neuromodulatory roles, Abeta peptides may have a normal physiological function in
      regulating neuron-glia signaling. Dysfunction of this signaling process may
      underlie glia-based aspects of AD pathogenesis. 

PMID- 23948933
TI  - Analysis of HSPA8 and HSPA9 mRNA expression and promoter methylation in the brain
      and blood of Alzheimer's disease patients.
AB  - Alzheimer's disease (AD) is the most common form of dementia in elderly.
      Chaperones may have a crucial role in AD due to their involvement in protein
      quality control, folding, and degradation. In this study, we investigated the
      mRNA and promoter DNA methylation levels of two chaperones, HSPA8 and HSPA9, in
      postmortem brain tissue (entorhinal and auditory cortices and hippocampus) from
      healthy elderly and AD subjects as well as in peripheral blood of healthy elderly
      and AD patients. mRNA quantification was performed by qRT-PCR and DNA methylation
      by mass spectrometry. In the peripheral blood, we did not observe a significant
      difference in HSPA8 and HSPA9 expression between elderly controls and AD. A
      significant downregulation of HSPA8 and HSPA9 was observed in AD across the three
      brain regions compared to the controls, suggesting their participation in AD
      pathogenesis. However, no important DNA methylation differences were observed,
      suggesting that other mechanism may be involved in controlling these genes
      expression. 

PMID- 23948934
TI  - Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808.
AB  - Aggregates of hyperphosphorylated tau (PHF-tau), such as neurofibrillary tangles,
      are linked to the degree of cognitive impairment in Alzheimer's disease. We have
      recently reported early clinical results of a novel PHF-tau targeting PET imaging
      agent, [F18]-T807. Since then, we have investigated a second novel PHF-tau
      targeting PET imaging agent, [F18]-T808, with different pharmacokinetic
      characteristics, which may be favorable for imaging Alzheimer's disease and other
      tauopathies. Here, we describe the first human brain images with [F18]-T808. 

PMID- 23948935
TI  - RNA interference-mediated knockdown of long-form phosphodiesterase-4D (PDE4D)
      enzyme reverses amyloid-beta42-induced memory deficits in mice.
AB  - Phosphodiesterase-4 (PDE4) inhibitors enhance memory, increase hippocampal
      neurogenesis, and reverse amyloid-beta (Abeta)-induced memory deficits. Here, we
      examined whether long-form PDE4D knockdown by lentiviral RNA construct containing
      a specific microRNA/miRNA-mir hairpin structure (4DmiRNA) reversed memory
      impairment caused by amyloid-beta1-42 (Abeta42) in mice using the Morris water
      maze (MWM) and novelty object recognition tests. Western blotting analysis was
      used to assess protein levels of cAMP response element-binding protein (CREB,
      unphosphorylated and phosphorylated [pCREB]), brain-derived neurotrophic factor
      (BDNF), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha),
      and nuclear factor-kappaB (NF-kappaB) to explore the neurochemical mechanisms.
      Aggregated Abeta42 (0.5 MUg/side) bilaterally infused in dentate gyrus decreased
      cAMP levels (p < 0.01) and produced memory deficits in the MWM (p < 0.01) and
      object recognition tests (p < 0.01). Microinfusions of lentiviruses resulted in
      downregulated expression of PDE4D4 and 4D5 proteins and reversed Abeta42-induced
      cAMP decline (p < 0.05) and memory deficits. Treatment also concomitantly
      increased pCREB (p < 0.05) and BDNF (p < 0.01) and reduced IL-1beta (p < 0.05),
      TNF-alpha (p < 0.01), and NF-kappaB (p65) (p < 0.05) in the hippocampus of
      Abeta42-challenged mice. These results suggest that long-form PDE4D knockdown may
      offer a promising treatment for memory loss associated with Alzheimer's disease. 

PMID- 23948936
TI  - Multiple microbleeds are related to cerebral network disruptions in patients with
      early Alzheimer's disease.
AB  - BACKGROUND: Cerebral microbleeds are a manifestation of small vessel disease and
      are common in patients with Alzheimer's disease (AD). However, their clinical
      significance in this condition is uncertain. We hypothesized that microbleeds
      contribute to disturbances of the cerebral network in AD and as such may affect
      cognition. OBJECTIVE: The goal of this study was to examine the relationship
      between microbleeds and brain networks in patients with amnestic mild cognitive
      impairment (aMCI) or early AD. METHODS: Sixty-seven patients (77.9 +/- 7.5 years)
      with aMCI (n = 29) or early AD (n = 38) underwent cognitive testing and 3Tesla
      MRI. Microbleeds were rated visually. Diffusion tensor imaging and graph
      theoretical analysis were used to reconstruct brain networks and to quantify
      network efficiency for each patient. Network measures were compared between
      patients without and with >=1 microbleeds and between patients without or with
      >=3 microbleeds. In secondary analyses, cognitive functioning was compared
      between groups. Analyses were adjusted for age and gender, and additionally for
      other markers of small vessel disease and atrophy. RESULTS: Network measures did
      not differ between patients with >=1 microbleed (n = 26) and patients without
      microbleeds (n = 41). However, patients with >=3 microbleeds (n = 11) showed
      significant white matter disruptions, longer path length, and less global
      efficiency than patients without microbleeds, independent of other markers of
      small vessel disease and atrophy. Cognitive functioning did not differ between
      patients without microbleeds and patients with >=1 or >=3 microbleeds.
      CONCLUSION: Multiple microbleeds are related to structural network disruption in
      patients with early AD, but their direct impact on cognitive functioning appears
      to be limited.

PMID- 23948937
TI  - Midlife and late-life body mass index and late-life dementia: results from a
      prospective population-based cohort.
AB  - BACKGROUND: Obesity has been consistently associated with dementia. The role of
      certain risk factors of dementia may change during life, and the importance of
      having a life-course perspective has been acknowledged. OBJECTIVE: The aim of
      this study was to investigate the association of midlife and late-life body mass
      index (BMI) with late-life dementia/Alzheimer's disease (AD) and whether the
      association was independent of other obesity-related co-morbidities. METHODS: The
      association between midlife BMI (mean age 50.2, SD 6.0) and late-life BMI (mean
      age 71.2, SD 4.0) and incident dementia later in life (mean age 75.7, SD 5.0)
      were investigated among 1,304 participants of the longitudinal population-based
      Cardiovascular risk factors, Aging and Dementia (CAIDE) study, conducted in
      Eastern Finland. The duration of follow-up was 26 years. The diagnosis of
      dementia was based on DSM-IV criteria and the probable and possible AD on the
      NINCDS-ADRDA criteria. RESULTS: Higher midlife BMI was associated with higher
      risk of incident dementia (adjusted HR, 95% CI 1.07, 1.00-1.14). However,
      decrease in BMI from midlife to late-life was associated with higher risk of
      dementia (1.14, 1.03-1.25 for one-unit decrease) and AD (1.20, 1.09-1.33). High
      late-life BMI was associated with lower risk of AD (0.89, 0.81-0.98) but the
      association with dementia was less evident (0.94, 0.86-1.03). CONCLUSION: Higher
      midlife BMI is related to higher risk of dementia and AD, independently of
      obesity-related risk factors and co-morbidities. Steeper decrease of BMI and low
      late-life BMI are associated with higher risk of dementia and AD. These findings
      highlight the importance of life-course perspective when assessing the
      association between BMI and cognition.

PMID- 23948939
TI  - The Cleveland Clinic Lou Ruvo Center for Brain Health: keeping memory alive.
AB  - The Cleveland Clinic Lou Ruvo Center for Brain Health (LRCBH) is a unique
      clinical and translational research enterprise that stems from the passion of
      Larry Ruvo to honor his father, Lou, a victim of Alzheimer's disease (AD). To
      attract national attention to AD, Mr. Ruvo convinced architect Frank Gehry to
      construct the remarkable building complex of the LRCBH in Las Vegas, Nevada.
      Cleveland Clinic assumed responsibility for running the clinical and research
      aspects of the LRCBH. The care provided in this novel architectural setting is
      innovative and emphasizes patients first care with integration of caregiver
      programs and clinical research opportunities. Standardization of care, outcomes
      measures, and process metrics provide a platform for assessing, studying, and
      exporting best practices in cognitive care. Clinical trials empower patients to
      help solve the diseases that afflict them. The combination of a passionate
      founder, dramatic architecture, clinical excellence, integrated care partner
      programs, and commitment to development of next generation treatments makes the
      LRCBH a unique model of integrated care and research. 

PMID- 23948938
TI  - Involvement of insulin-degrading enzyme in insulin- and atrial natriuretic
      peptide-sensitive internalization of amyloid-beta peptide in mouse brain
      capillary endothelial cells.
AB  - Cerebral clearance of amyloid-beta peptide (Abeta), which is implicated in
      Alzheimer's disease, involves elimination across the blood-brain barrier (BBB),
      and we previously showed that an insulin-sensitive process is involved in the
      case of Abeta1-40. The purpose of this study was to clarify the molecular
      mechanism of the insulin-sensitive Abeta1-40 elimination across mouse BBB. An in
      vivo cerebral microinjection study demonstrated that [125I]hAbeta1-40 elimination
      from mouse brain was inhibited by human natriuretic peptide (hANP), and
      [125I]hANP elimination was inhibited by hAbeta1-40, suggesting that hAbeta1-40
      and hANP share a common elimination process. Internalization of [125I]hAbeta1-40
      into cultured mouse brain capillary endothelial cells (TM-BBB4) was significantly
      inhibited by either insulin, hANP, other natriuretic peptides or insulin
      degrading enzyme (IDE) inhibitors, but was not inhibited by phosphoramidon or
      thiorphan. Although we have reported the involvement of natriuretic peptide
      receptor C (Npr-C) in hANP internalization, cells stably expressing Npr-C
      internalized [125I]hANP but not [125I]hAbeta1-40, suggesting that there is no
      direct interaction between Npr-C and hAbeta1-40. IDE was detected in plasma
      membrane of TM-BBB4 cells, and internalization of [125I]hAbeta1-40 by TM-BBB4
      cells was reduced by IDE-targeted siRNAs. We conclude that elimination of hAbeta1
      40 from mouse brain across the BBB involves an insulin- and ANP-sensitive
      process, mediated by IDE expressed in brain capillary endothelial cells. 

PMID- 23948940
TI  - Of rodents and men: the mysterious interneuronal pilgrimage of misfolded protein
      tau in Alzheimer's disease.
AB  - Neurofibrillary degeneration, driven by misfolded protein tau, spreads from the
      predisposed induction sites and advances in a topographically predictable
      sequence along connected brain areas. Several mouse model studies have
      demonstrated that some species of pathologically modified tau, namely insoluble
      fibrils and soluble oligomers, evoke propagation of the pathology. These results
      clearly show that the spreading potency of misfolded tau does not depend
      exclusively on its solubility and/or mutations. The candidate factor responsible
      for the progression of misfolded protein tau is its disease modified
      conformation. In this study, we address the question, whether insoluble tau
      complexes containing either 3R or 4R human misfolded truncated tau (AlzTau)
      command distinct infectivity and spreading potency. We found that insoluble tau
      isolated from transgenic rats (SHR24), expressing misfolded 3R AlzTau, was able
      to infect cortical neurons in the area of injection in SHR72 transgenic rats
      expressing 4R AlzTau. However this tau was not able to spread into other brain
      areas. In contrast, administration of insoluble tau isolated from SHR72
      transgenic rats was not only able to infect cortical neurons but also induced
      extensive spreading of neurofibrillary tangles in the adjacent brain areas. These
      findings suggest the existence of various strains of disease modified tau, tauons
      displaying different infectivity and spreading potency. Furthermore, the
      presented rat tauopathy models could serve as a tool for identification and
      characterization of tauons isolated from Alzheimer's disease brains that would
      allow stratification of Alzheimer's disease patients. 

PMID- 23948941
TI  - Insulin/IGF signaling-related gene expression in the brain of a sporadic
      Alzheimer's disease monkey model induced by intracerebroventricular injection of
      streptozotocin.
AB  - We reported previously that the intracerebroventricular streptozotocin (icv-STZ)
      treated cynomolgus monkey showed regionally specific glucose hypometabolism in
      FDG-PET imaging, similar to that observed in the early stages of sporadic
      Alzheimer's disease (sAD). However, further pathological analyses of this model
      at the molecular level are needed to validate it as a feasible model for sAD. Two
      cynomolgus monkeys were injected with 2 mg/kg STZ into the cerebellomedullary
      cistern at day 1, 7 and 14. Two control monkeys were given normal saline. At 5
      months after injection, the expression levels of genes encoding 9 upstream
      molecules in insulin/insulin-like growth factor (IGF) signaling and markers for 4
      cell-type populations in the frontal cortex, hippocampus, posterior cingulate,
      precuneus, and occipital cortex of control and icv-STZ treated cynomolgus monkeys
      were examined. Real-time quantitative PCR analyses demonstrated that the overall
      mRNA expression of insulin/IGF signaling-related genes was mainly impaired in the
      anterior part of the cerebrum, frontal cortex, and hippocampus, similar to the
      early stage of sAD. The changes were accompanied by the loss of oligodendrocytes
      and neurons. The posterior part of the cerebrum did not show degenerative
      alterations. The present study provides important fundamental information on the
      icv-STZ monkey model for sAD. These results may help guide future studies using
      this model for the investigation of pathological mechanisms and the development
      of drugs for sAD. 

PMID- 23948942
TI  - Bindarit, inhibitor of CCL2 synthesis, protects neurons against amyloid-beta
      induced toxicity.
AB  - One of the hallmarks of Alzheimer's disease (AD), the most common age-related
      neurodegenerative pathology, is the abnormal extracellular deposition of
      neurotoxic amyloid-beta (Abeta) peptides that accumulate in senile plaques. Abeta
      aggregates are toxic to neurons and are thought to contribute to neuronal loss.
      Evidence indicates that inflammation is involved in the pathophysiology of AD,
      and activation of glial cells by a variety of factors, including Abeta, appears
      to be a central event. Among molecules produced during inflammation associated
      with neuronal death, CCL2, also known as monocyte chemotactic protein-1 (MCP-1),
      seems to be particularly important. Indeed, CCL2 levels are higher in the
      cerebrospinal fluid of patients with AD than in controls. In the present study,
      we demonstrated the protective effect of bindarit (which inhibits CCL2 synthesis)
      against both Abeta25-35 and Abeta1-42-induced toxicity in primary mixed neural
      cultures. Bindarit (30-500 MUM) reversed cell death induced by Abeta in a dose
      dependent manner and reduced the transcription and release of CCL2 by astrocytes
      after Abeta treatment, as revealed by qRT-PCR, ELISA, and immunofluorescence
      staining. Astroglial activation and CCL2 release was induced by ATP released by
      damaged neurons through interaction with P2X7 receptors present on astrocyte
      surface. CCL2, interacting with its cognate receptor CCR2, present on neuron
      surface, strongly contributes to the toxic activity of Abeta. Bindarit was able
      to disconnect this neuro-glial interaction. Our results demonstrate the ability
      of bindarit to inhibit Abeta-induced neuronal death and suggest the potential
      role of CCL2 inhibitors in the treatment of neuroinflammatory/neurodegenerative
      diseases. 

PMID- 23948943
TI  - Cellular prion protein as a therapeutic target in Alzheimer's disease.
AB  - Soluble oligomeric species of amyloid-beta (Abeta) peptide are presumed to be
      drivers of synaptic impairment, and the resulting cognitive dysfunction in
      Alzheimer's disease. In 2009, cellular prion protein (PrPC) was identified in a
      genome-wide screen as a high-affinity receptor for Abeta oligomers, and since
      then, many studies have explored the role of PrPC in Alzheimer's disease. Herein,
      I systematically assess the current level of target validation for PrPC in
      Alzheimer's disease and the merits of the identified approaches to
      therapeutically affect the PrPC:Abeta oligomer-interaction. The interaction of
      Abeta oligomers with PrPC in mice impairs hippocampal long-term potentiation,
      memory, and learning in a manner that involves Fyn, tau, and glutamate receptors.
      Furthermore, PrPC acts to catalyze the formation of certain Abeta oligomeric
      species in the synapse and may mediate the toxic effects of other beta-sheet rich
      oligomers as well. Therapeutic approaches utilizing soluble PrPC ectodomain or
      monoclonal antibodies targeting PrPC can at least partially prevent the
      neurotoxic effects of Abeta oligomers in mice. 

PMID- 23948944
TI  - Can rituximab induce long-term disease remission in patients with intra-ocular
      non-infectious inflammation?
AB  - Treatment of non-infectious uveitis is based primarily on the use of systemic
      corticosteroids and second-line immunosuppressive drugs. However, their extensive
      side effect profile, particularly for steroids, has led to the increased use of
      other immunosuppressive drugs, as sparing capacity agents. Rituximab is an anti
      CD20 chimeric antibody, often given as a single course of 2 infusions, resulting
      in complete depletion of peripheral mature B cells. While it is licensed to treat
      refractory systemic lymphoma patients, it has also shown promising results in
      systemic auto-immune diseases, where a single course of treatment is able to
      achieve long-term clinical remission. Treatment with rituximab has been reported
      for various ocular conditions, suggesting it may be effective in inducing long
      term disease control and other systemic immunosuppressive agents can be reduced
      or discontinued. When disease relapse occurs, a further course or courses can be
      given with good results. This review summarizes the current evidence regarding
      the role of rituximab in treating non-infectious uveitis.

PMID- 23948945
TI  - Effect of pretreatment on Er:YAG laser-irradiated dentin.
AB  - Erbium:yttrium-aluminum-garnet (Er:YAG) laser preparation of tooth cavities for
      restoration is an increasingly popular method, but its compatibility with
      existing composite material bonding protocols has not been fully defined. This
      study evaluated the effect of laser and etchant pretreatments on the performance
      of one-bottle self-etch adhesives in Er:YAG laser-prepared dentin. Eight groups
      of 20 extracted teeth were established to investigate bonding in tested dentin
      disks. Various combinations of laser preparation (with/without), pretreatment
      (none/acid-etch/low-fluence Er:YAG irradiation), and self-etching adhesive (G
      Bond Plus or Xeno V) were tested. Samples were then restored with composite resin
      and subjected to a tensile bond strength (TBS) test. We also performed scanning
      electron microscopy (SEM) on dentin disks from some of these groups before and
      after adhesive application to evaluate their microscopic morphological
      appearance. Statistical analysis (Dunnett T3 test coupled with the general linear
      model at 5% significance level) revealed that the laser preparation of dentin did
      not impact on TBS (p = 0.914), whereas pretreatment with either phosphoric acid
      (p < 0.0001) or low-fluence Er:YAG laser irradiation (p < 0.0001) significantly
      increased TBS, although there was no difference between them in their respective
      elevation of TBS. SEM analysis demonstrated that both acid and laser
      pretreatments reduced irregularities and produced a more homogeneous surface.
      Er:YAG laser preparation does not compromise the efficacy of one-step self-etch
      dentin adhesives, and pretreatment with phosphoric acid or low-fluence Er:YAG
      laser can significantly increase the TBS of adhesion to this irradiated dentin.

PMID- 23948946
TI  - Liquid crystal-on-organic field-effect transistor sensory devices for perceptive
      sensing of ultralow intensity gas flow touch.
AB  - We demonstrate liquid crystal-on-organic field-effect transistor (LC-on-OFET)
      sensory devices that can perceptively sense ultralow level gas flows. The LC-on
      OFET devices were fabricated by mounting LC molecules (4-cyano-4'-pentylbiphenyl 
      5CB) on the polymer channel layer of OFET. Results showed that the presence of
      LC molecules on the channel layer resulted in enhanced drain currents due to a
      strong dipole effect of LC molecules. Upon applying low intensity nitrogen gas
      flows, the drain current was sensitively increased depending on the intensity and
      time of nitrogen flows. The present LC-on-OFET devices could detect extremely low
      level nitrogen flows (0.7 sccm-11 MUl/s), which could not be felt by human skins,
      thanks to a synergy effect between collective behavior of LC molecules and charge
      sensitive channel layer of OFET. The similar sensation was also achieved using
      the LC-on-OFET devices with a polymer film skin, suggesting viable practical
      applications of the present LC-on-OFET sensory devices.

PMID- 23948947
TI  - Effect of pterygium on contrast sensitivity.
AB  - The purpose of this study is to evaluate the effect of pterygium on contrast
      sensitivity. Thirty-six eyes with pterygium and 18 eyes without pterygium were
      included in the study. The size of the pterygium was measured on the slit lamp
      both vertically at the limbus and categorized into three groups (<=3, 3.1 to <=5,
      >5 mm), and horizontally on the cornea and categorized into two groups (0.5 to
      <=2, >2 mm), and the area calculated by multiplying the two measurements was then
      categorized into three groups (<=7, 7.1 to <=14, >14 mm(2)). Contrast sensitivity
      was measured using CSV-1000E charts (Vector Vision) at 3, 6, 12 and 18 cycles per
      degree under photopic and mesopic conditions. The mean vertical length of
      pterygium was 4.41 +/- 1.12 mm, mean horizontal width was 2.09 +/- 0.68 mm and
      mean area was 9.7 +/- 5.01 mm(2). Significant differences in both photopic and
      mesopic contrast sensitivities at all frequencies were noted between normal eyes
      and vertical length of pterygium >3 mm, horizontal width >=0.5 mm and area >7
      mm(2). Contrast sensitivity had significant negative correlation with all three
      parameters. Pterygium with vertical length >3 mm, horizontal width >=0.5 mm and
      area >7 mm(2) caused a significant decrease in both photopic and mesopic contrast
      sensitivity at all spatial frequencies. Contrast sensitivity had significant
      negative correlation with all three parameters.

PMID- 23948948
TI  - Intravitreal functional plasminogen is elevated in central retinal vein
      occlusion.
AB  - PURPOSE: To detect intravitreal functional plasminogen in vitreous samples of
      patients with recent onset of central retinal vein occlusion (CRVO) and to
      demonstrate significantly higher intravitreal plasminogen in CRVO patients in
      comparison to controls. METHODS: Prospective clinical case series of 13
      consecutive patients with recent onset of CRVO scheduled for core pars plana
      vitrectomy and 10 consecutive patients undergoing standard pars plana vitrectomy
      for routine macular surgery or vitreal floater removal. In all 23 cases, vitreous
      taps were extracted from the central vitreous body, and plasminogen was
      functionally determined in a new ultrasensitive p-nitroanilide reaction after
      activation with streptokinase (100% of normal, %N = functional plasminogen in
      pooled normal citrated plasma). RESULTS: Plasminogen was detected in all analyzed
      samples (n = 23), and mean plasminogen was revealed to be 1.33 +/- 1.73% (mean +/
      SD), with a range of 0.03-7.8%N. Patients with recent onset of CRVO exhibited
      significantly higher intravitreal plasminogen (2.19 +/- 1.89%N) in comparison to
      controls (0.20 +/- 0.21%N; p < 0.001, Mann-Whitney U test). CONCLUSION: Due to
      significantly increased intravitreal plasminogen in patients with recent onset of
      CRVO, intravitreally administered tissue plasminogen activator might be an option
      to induce posterior vitreous detachment (enzymatic vitreolysis) in CRVO patients.

PMID- 23948949
TI  - [Neonatal sepsis and meningitis due to Streptococcus pneumoniae].

PMID- 23948950
TI  - [Resistance to routine ophthalmological treatments in a patient with chronic
      blepharitis].

PMID- 23948951
TI  - Developing catalytic applications of cooperative bimetallics: competitive
      hydroamination/trimerization reactions of isocyanates catalysed by sodium
      magnesiates.
AB  - Mixed-metal reagents [NaMg(CH2SiMe3)3] (1) and [(THF)NaMg(NPh2)3(THF)] [3
      (THF)(2)] can act as precatalysts to selectively promote the
      hydroamination/trimerization of isocyanates (RNCO) depending on the steric bulk
      of the R substituent.

PMID- 23948952
TI  - Local orthogonality as a multipartite principle for quantum correlations.
AB  - In recent years, the use of information principles to understand quantum
      correlations has been very successful. Unfortunately, all principles considered
      so far have a bipartite formulation, but intrinsically multipartite principles,
      yet to be discovered, are necessary for reproducing quantum correlations. Here we
      introduce local orthogonality, an intrinsically multipartite principle stating
      that events involving different outcomes of the same local measurement must be
      exclusive or orthogonal. We prove that it is equivalent to no-signalling in the
      bipartite scenario but more restrictive for more than two parties. By exploiting
      this non-equivalence, it is then demonstrated that some bipartite supra-quantum
      correlations do violate the local orthogonality when distributed among several
      parties. Finally, we show how its multipartite character allows revealing the non
      quantumness of correlations for which any bipartite principle fails. We believe
      that local orthogonality is a crucial ingredient for understanding no-signalling
      and quantum correlations. 

PMID- 23948953
TI  - Accreditation Council for Graduate Medical Education accreditation and influence
      on perceptions of pediatric otolaryngology fellowship training experience.
AB  - IMPORTANCE: The American Society of Pediatric Otolaryngology (ASPO) has set a
      goal of universal accreditation of fellowship programs by the Accreditation
      Council for Graduate Medical Education (ACGME) by 2014. This study offers data
      comparing trainee experience at accredited vs nonaccredited programs. OBJECTIVE:
      To evaluate perceptions of pediatric otolaryngology fellowship training
      experience and to elucidate differences between those who trained in ACGME
      accredited fellowships vs those who did not. DESIGN AND PARTICIPANTS: Web-based
      survey sent to all members of ASPO, as well as recent fellowship graduate ASPO
      eligible physicians. Responses were obtained in an anonymous fashion. The study
      population comprised 136 ASPO members who recently graduated from pediatric
      otolaryngology fellowship programs (36 from ACGME-accredited fellowships and 100
      from nonaccredited programs). MAIN OUTCOMES AND MEASURES: Difference in perceived
      fellowship experience between graduates of accredited vs nonaccredited programs,
      specifically, differences in service vs education perceptions. RESULTS: Overall,
      a majority (64%) of respondents agreed that standardizing the pediatric
      fellowship curriculum through ACGME accreditation is a worthwhile goal. Those who
      attended ACGME-accredited fellowships were more likely to favor accreditation vs
      non-ACGME graduates (83% vs 58%; P = .006). Graduates of ACGME-accredited
      programs were also more likely to agree that their fellowship provided adequate
      preparation for a career in academic medicine (100% vs 89%; P = .04), protected
      time for research (94% vs 60%; P < .001), vacation and academic time (94% vs 78%;
      P = .03), and opportunities to formally evaluate their superiors (72% vs 32%; P <
      .001). Non-ACGME graduates reported higher primary call frequency (0.8 days per
      week vs 0.2 days per week; P = .01), and attending physician participation in
      rounds (71% vs 53%; P = .05). CONCLUSIONS AND RELEVANCE: Most respondents were in
      agreement with universal ACGME accreditation. Those having trained in accredited
      programs cite increased allowance for research, academic and vacation time, more
      formal opportunities to evaluate their faculty, and decreased primary call
      burden.

PMID- 23948954
TI  - The influence of pi-conjugated moieties on the thermodynamics of cooperatively
      self-assembling tricarboxamides.
AB  - A detailed investigation of the self-assembly behaviour of C3-symmetrical
      tricarboxamides reveals that a larger pi-conjugated core does not increase the
      stability of assemblies in an apolar solvent but makes the system more sensitive
      to destabilization by addition of a good solvent. 

PMID- 23948955
TI  - Preliminary results of cord blood mononuclear cell therapy for multiple system
      atrophy: a report of three cases.
AB  - OBJECTIVES: This study was designed to evaluate the effects of cord blood
      mononuclear cell transplantation in multiple system atrophy (MSA). CLINICAL
      PRESENTATION AND INTERVENTION: Cord blood mononuclear cells (1-2 * 10(8) cells/6
      ml) were injected into the subarachnoid space using lumbar puncture in patients 1
      and 2 and cisterna magna puncture in patient 3 in the 3 patients with MSA. The
      cord blood mononuclear cell transplantation was repeated 30 days after the first
      treatment in patients 1 and 2; it was repeated twice in patient 3. The clinical
      outcomes of treatment were used to assess the Unified Multiple System Atrophy
      Rating Scale (UMSARS) before, 90 and 180 days after the cell transplantation.
      There were no clinically noticeable side effects from the cord blood mononuclear
      cells. The UMSARS scores improved after 90 days of the cord blood mononuclear
      cell therapy in all 3 patients, the most significant improvement being that in
      urinary incontinence and ability to walk. CONCLUSIONS: Cord blood mononuclear
      cell transplantation was safe and potentially effective in the treatment of MSA
      in the 3 patients.

PMID- 23948956
TI  - In aggressive variants of non-Hodgkin lymphomas, Ezh2 is strongly expressed and
      polycomb repressive complex PRC1.4 dominates over PRC1.2.
AB  - Polycomb group (PcG) proteins are important for the regulation of hematopoiesis
      by regulating chromatin compaction and silencing genes related to differentiation
      and cell cycle. Overexpression of enhancer of zeste homologue 2 (Ezh2) and Bmi
      1/PCGF4 has been implicated in solid organ cancers, while Mel-18/PCGF2 has been
      reported as a tumor suppressor. Detailed expression profiles of PcG proteins and
      their diagnostic significance in malignant lymphomas are still unknown. In this
      study, we analyzed the expression levels of Ezh2, Bmi-1, Mel-18, and Ki67 in 197
      Hodgkin's and non-Hodgkin's lymphoma patient samples and in lymphoma cell lines
      using immunohistochemistry, fluorescent immunocytochemistry, and Western
      blotting. Immunohistochemical staining showed that Ezh2 expression was
      significantly increased in aggressive compared to indolent subtypes of B cell
      neoplasms (P = 0.000-0.030), while no significant differences in Bmi-1 expression
      were found between these subtypes. Compared to the normal counterpart, T cell
      lymphomas showed significant overexpression of Bmi-1 (P = 0.011) and Ezh2 (P =
      0.000). The Ki67 labeling index showed a positive correlation with Ezh2
      expression in B cell lymphomas (correlation coefficient (Co) = 0.983, P = 0.000)
      and T/NK cell lymphomas (Co = 0.629, P = 0.000). Fluorescent immunohistochemical
      staining showed coexpression of Ezh2 and Ki67 in the same tumor cells, indicating
      that Ezh2 expression correlates with cell proliferation. Both B and T/NK cell
      neoplasms showed low expression of Mel-18 and high expression of both Bmi-1 and
      Ezh2. In conclusion, in aggressive lymphoma variants, Ezh2 is strongly expressed
      and polycomb repressive complex PRC1.4 dominates over PRC1.2. Coexpression of Bmi
      1 and Ezh2 is a characteristic of aggressive lymphomas. Ezh2 correlates with the
      proliferation and aggressive nature of non-Hodgkin's lymphomas.

PMID- 23948957
TI  - Histopathology of prostate tissue after vascular-targeted photodynamic therapy
      for localized prostate cancer.
AB  - Low-risk prostate adenocarcinoma is classically managed either with active
      surveillance or radical therapy (such as external radiotherapy or radical
      prostatectomy), but both have significant side effects. Vascular-targeted
      photodynamic therapy (VTP) is a focal therapy proposed as an alternative approach
      for localized, low-volume, and low-Gleason score (<=6) carcinomas. We report
      histological modifications observed in prostate biopsies of 56 patients,
      performed 6 months after VTP using the photosensitizer TOOKAD(r) Soluble (WST11)
      and low-energy laser administered in the tumor area transperineally by optic
      fibers. In 53 patients, we observed sharply demarcated hyaline fibrotic scars,
      with or without rare atrophic glands, sometimes reduced to corpora amylacea
      surrounded by giant multinuclear macrophages. Mild chronic inflammation,
      hemosiderin, and coagulative necrosis were also observed. When residual cancer
      was present in a treated lobe (17 patients), it was always located outside the
      scar, most often close to the prostate capsule, and it showed no therapy-related
      modification. Histopathological interpretation of post-WST11 VTP prostate
      biopsies was straightforward, in contrast with that of prostate biopsies after
      radio or hormonal therapy, which introduces lesions difficult to interpret. VTP
      resulted in complete ablation of cancer in the targeted area. 

PMID- 23948958
TI  - Stent thrombosis after coronary stent implantation: a protective effect of high
      dose statin therapy?
AB  - OBJECTIVES: To assess independent predictors of stent thrombosis (ST) in an all
      comer trial. METHODS: This is an observational case-control study based on a
      retrospective analysis of the Basel Stent Kosten Effektivitats Trial (BASKET) (n
      = 826). Patients with ST were compared to controls with regard to baseline
      parameters. Multivariate models were performed to identify independent predictors
      of ST. RESULTS: At 36 months, there were 53 (6.4%) patients with ST, 17 (32%) of
      whom had early ST and 36 (68%) of whom had late/very late ST. Patients with ST
      were at a higher cardiovascular risk but received lower doses of statins than the
      controls (n = 212). Stents in ST patients were longer, had more overlap and were
      not as well expanded, with significantly more remaining stenoses than the stents
      in the controls. Multivariable analysis revealed interventions in saphenous vein
      grafts, malapposed stents, an overlap >3 mm, complex coronary anatomy and
      treatment with low-dose/no statins as risk factors for ST, while interventions in
      saphenous vein grafts, underexpanded or malapposed stents, a history of
      myocardial infarction and treatment with low-dose/no statins were risk factors
      for late ST. CONCLUSIONS: The use of statins might have a protective effect
      against ST. This observation is new, hypothesis-generating and should be
      evaluated in an adequately powered randomized trial.

PMID- 23948959
TI  - Gadd45beta is transcriptionally activated by p53 via p38alpha-mediated
      phosphorylation during myocardial ischemic injury.
AB  - Growth arrest and DNA damage-inducible 45beta (Gadd45beta) have been shown to
      play a role in inducing cardiomyocyte apoptosis under ischemia/anoxia. The well
      known transcription factor p53 is known to cause apoptosis in cardiomyocytes
      under ischemia. Based on the common role of Gadd45beta and p53 in ischemia
      induced apoptosis, we investigated whether p53 is involved in the mechanisms
      responsible for Gadd45beta expression in both in vitro and in vivo models of
      ischemic heart injury. A chromatin immunoprecipitation assay revealed direct
      binding of p53 to the Gadd45beta promoter region during anoxia, and this binding
      was confirmed by surface plasmon resonance imaging. In rat heart-derived H9c2
      cells, silencing of p53 abrogated the increase of Gadd45beta promoter-luciferase
      reporter (Gadd45beta-Luc) activity and the expression of Gadd45beta under anoxia
      and overexpression of p53 enhanced Gadd45beta-Luc activity and Gadd45beta
      expression. Gadd45beta mRNA and protein expression were significantly inhibited
      by p53 siRNA in a rat ischemic heart model. In addition, p38alpha-mediated
      phophorylation of p53 at both Ser15 and Ser20 was shown to be essential for the
      expression of Gadd45beta mRNA and protein during anoxia. These results reveal the
      p38alpha-p53-Gadd45beta axis as a novel signaling module in the anoxia-induced
      apoptotic death pathway. In conclusion, this study provides molecular evidence
      that Gadd45beta is a novel downstream target gene of p53 under ischemia/anoxia
      and suggests the therapeutic potential of targeting Gadd45beta as a treatment of
      ischemic heart injury. KEY MESSAGE: Gadd45beta is transcriptionally induced by
      p53 via direct binding under ischemia/anoxia. The induction of Gadd45beta
      expression requires the p53 phosphorylation at Ser15/Ser20. p38alpha mediates the
      p53 phosphorylation at Ser15/Ser20 and the Gadd45beta expression. Ischemia/anoxia
      p38alpha-p53-Gadd45beta axis serves as a novel apoptotic signaling module.

PMID- 23948960
TI  - Do locking screws work in plates bent at holes?
AB  - OBJECTIVES: To assess whether plate bending at a hole significantly changes the
      biomechanical properties of a locked screw. METHODS: Coronal plane bends of 5-,
      15-, or 45-degree angles were placed in 3.5-mm locking compression plates with
      the apex at a locking hole. An additional 45-degree angle test group was created
      in which a threaded screw head insert was placed before bending. Ten plates were
      tested in each group and compared with nonbent controls in a stepwise cyclic
      loading protocol. RESULTS: Statistically significant differences in protocol
      survival were shown between the control group and the 15-degree angle (P = 0.006)
      and 45-degree angle (P = 0.0007) groups. An apparent decrease in protocol
      survival in the 5-degree angle group did not reach statistical significance (P =
      0.17). The average number of cycles survived was significantly different between
      the control group and the 15-degree angle (P = 0.027) and 45-degree angle (P =
      0.0002) groups. The mean cycles to failure for the 5-degree angle group was 16%
      lower than for controls but did not reach statistical significance (P = 0.37).
      The test group bent to an angle of 45 degrees after placement of a threaded screw
      head insert showed no difference in protocol survival or in mean number of cycles
      survived compared with the regular 45-degree angle group. CONCLUSION: Bending of
      a 3.5-mm locking compression plate by more than 5 degrees at a locking hole
      results in a statistically significant decrease in survival of the corresponding
      locked screw. This effect cannot be prevented by the placement of a threaded
      screw head insert before bending.

PMID- 23948961
TI  - Local antibiotic delivery by a bioabsorbable gel is superior to PMMA bead depot
      in reducing infection in an open fracture model.
AB  - OBJECTIVES: Local delivery allows a high concentration of antibiotics to be
      achieved in the wound while avoiding the side effects and cost of systemic
      administration. Beads molded from polymethylmethacrylate cement are commonly used
      for local antibiotic delivery but are not ideal. The purpose of this study was to
      determine whether a bioabsorbable gel delivering vancomycin and gentamicin is
      more effective in reducing infection than beads delivering vancomycin and
      tobramycin. METHODS: This study used a segmental defect rat model contaminated
      with Staphylococcus aureus and treated with clinically relevant local antibiotic
      doses, delivered by gel or beads. In the gel group, 1 mL of gel containing
      gentamicin and vancomycin was spread throughout the wound. In the bead group,
      four 3-mm beads containing tobramycin and vancomycin were placed in the wound, 2
      in the defect and 2 in the adjacent tissue envelope, there was also a control
      group that received no antibiotic treatment. After 14 days, bone and hardware was
      harvested for separate microbiological analysis. RESULTS: There was a
      significantly lower infection rate in groups treated with antibiotics delivered
      by gel compared with those treated with either antibiotic beads or no antibiotics
      at all (P < 0.001). Quantitative cultures also demonstrate significantly less
      bacteria in the wounds treated with the gel than in the control or bead groups (P
      <= 0.004). CONCLUSIONS: These results suggest that antibiotic delivery by a gel
      is superior to beads. The authors propose that antibiotic depot by
      polymethylmethacrylate antibiotic beads is less effective because this method has
      to rely on diffusion of the antibiotic from the high concentration close to the
      beads to all regions of the wound.

PMID- 23948962
TI  - Lab-on-chip device for single cell trapping and analysis.
AB  - Traditional cell assay gives us an average result of multiple cells and it is
      assumed that the resultant is the outcome of all cells in population. However,
      single cell studies have revealed that individual cells of same type may differ
      dramatically and these differences may have important role to play in cells
      functionality. Such information can be obscured in only studying cell population
      experimental approach. To uncover biological principles and ultimately to improve
      the detection and treatment of disease, new approaches are highly required to
      single cell analysis. We propose to fabricate a lab on chip device to study high
      throughput single cell nanotoxicity analysis. The chip incorporates independently
      addressable active microwell electrodes for cell manipulation and analysis. We
      employed positive-dielectrophoresis approach to quickly and efficiently capture
      single cells in each wells with having control over individual microwells. We
      examined change in impedance properties to verify cell capture in microwell and
      its health and present a novel model of single cell assay for nanotoxicity, and
      drug testing. 

PMID- 23948964
TI  - Pulmonary aspergillosis and aflatoxins in chronic lung diseases.
AB  - Fungal infections of lung have become increasingly common during the last few
      decades. Aspergillosis and the role of aflatoxins in various chronic lung
      diseases have not been extensively studied. Bronchoalveolar lavage (BAL) samples
      and sera from 40 patients of chronic lung diseases were analyzed for
      galactomannan antigen (GM) and aflatoxin by enzyme-linked immunosorbent assay.
      Direct microscopy and culture of BAL samples were also done to detect the
      Aspergillus species. Results revealed that 15 (37.5 %) of the 40 patients had
      growth of Aspergillus on BAL culture. Out of these culture-positive cases, 13
      (86.7 %) patients were positive for galactomannan antigen also. About 62.5 %
      cases did not show growth of Aspergillus in BAL culture. However, galactomannan
      antigen could be detected in 20 % of these patients. Overall, 20 % patients were
      diagnosed as proven invasive fungal disease (IFD), 32.5 % were of probable IFD,
      17.5 % of possible IFD. Aspergillus growth was observed in 100 % of proven and
      53.8 % of probable IFD cases. Galactomannan antigen was found in 100 % cases of
      proven and 76.9 % of probable IFD. Ten (25 %) patients were found to be positive
      for aflatoxins. It was detected in 6 (40 %) of culture-positive cases. About 62.5
      % of the cases with proven IFD and 46.1 % of probable IFD had aflatoxin in their
      samples. Aflatoxin positivity was found to be more in patients with proven IFD
      than in probable IFD, and higher level of aflatoxins was detected in cases with
      proven IFD. Significant difference was observed in aflatoxin positivity among
      food grain workers when compared to other occupations. 

PMID- 23948965
TI  - Comparison of dermatophyte PCR kit with conventional methods for detection of
      dermatophytes in skin specimens.
AB  - The laboratory diagnosis of dermatophytosis is usually based on direct
      microscopic examination and culturing of clinical specimens. A commercial
      polymerase chain reaction kit (Dermatophyte PCR) has had favorable results when
      used for detection of dermatophytes and identification of Trichophyton rubrum in
      nail specimens. This study investigated the efficacy of the Dermatophyte PCR kit
      for detecting dermatophytosis in 191 hair or skin specimens from patients with
      suspected dermatophytosis. PCR was positive for 37 % of samples, whereas 31 and
      39 % of the specimens were positive by culturing and direct microscopy,
      respectively. The sensitivity, specificity, positive predictive value, and
      negative predictive value for PCR analysis were 83, 84, 71, and 91 %,
      respectively. The sensitivity of the PCR test was higher in specimens obtained
      from skin (88 %) than in those obtained from hair (58 %), while the specificity
      remained almost the same (84 and 86 % for skin and hair, respectively). Our
      results show that the Dermatophyte PCR kit is a promising diagnostic tool for
      detection of dermatophytosis in skin samples, providing clinicians with a rapid
      diagnosis. 

PMID- 23948966
TI  - Anterior and pan-endophthalmitis caused by Candida albicans and Aspergillus
      fumigatus: report of two cases.
AB  - We report two posttraumatic fungal endophthalmitis cases with anterior and entire
      segment involvement caused, respectively, by Candida albicans and Aspergillus
      fumigatus. The anterior endophthalmitis induced by C. albicans presented
      multifocal lesions with hyphael structures in anterior chamber, but without
      involvement of posterior vitreous. The pan-endophthalmitis caused by A. fumigatus
      displayed significant hypopyon and vitritis. Treatment strategies are anterior
      chamber cleaning for anterior endophthalmitis and vitrectomy for pan
      endophthalmitis, excepting systemic and topical antifungal drug applications
      including intravitreal injection for both types of endophthalmitis. There is a
      much better outcome in the case with anterior segment involvement than that with
      entire segment involvement. This case report provides evidence that the different
      types of posttraumatic fungal endophthalmitis related to different fungal
      infections indeed existed and should be managed with different strategies. 

PMID- 23948967
TI  - Evaluation for the clinical diagnosis of Pythium insidiosum using a single-tube
      nested PCR.
AB  - Pythiosis is a rare infectious disease caused by Pythium insidiosum, which
      typically occurs in tropical and subtropical regions. The high mortality rate may
      be in consequence of the lack of diagnosis. The objective of this study was to
      evaluate reliability of a new single-tube nested PCR for detection of P.
      insidiosum DNA. A total of 78 clinical isolates of various fungi and bacteria,
      106 clinical specimens and 80 simulated positive blood samples were tested. The
      developed primer pairs CPL6-CPR8 and YTL1-YTR1 are located on 18S subunit of the
      rRNA gene of P. insidiosum. The specificity, negative and positive predictive
      values were 100, 100 and 87.5 %, respectively, as compared with direct microscopy
      and cultivation. The detection limit of the single-tube nested PCR was 21
      zoospores corresponding to 2.7 pg of the DNA. The results demonstrate that the
      new single-tube nested PCR offers a highly sensitive, specific and rapid genetic
      method for detecting P. insidiosum. 

PMID- 23948968
TI  - Robotic versus laparoscopic surgery for mid-low rectal cancer after neoadjuvant
      chemoradiation therapy: comparison of oncologic outcomes.
AB  - PURPOSE: Minimal invasive surgery for mid and low rectal cancer after neoadjuvant
      long-course chemoradiotherapy (LCRT) can be challenging. The aim of our study was
      to compare outcomes of laparoscopic and robotic resections in mid and low rectal
      cancers after LCRT. METHODS: Between Jan 2006 and Dec 2010, all patients who
      underwent robotic or laparoscopic resections for mid and low rectal cancers after
      LCRT were identified from a prospective database. These patients received
      treatment (5FU-based chemotherapy, 50.4 Gy radiotherapy), as they were T3 or T4
      and/or node + ve. Patients in the two groups were compared with respect to
      demographics, clinical safety, and oncological outcomes. RESULTS: One hundred
      thirty-eight patients underwent rectal cancer resection after LCRT, either
      robotic (n = 74) or laparoscopic (n = 64). The patients in both groups were
      comparable in terms of demographics, distance of tumor from anal verge, and type
      of procedures. There were four (6.3 %) conversions in laparoscopic group and one
      (1.4 %) in the robotic group (p = 0.183). The morbidity rates in the laparoscopic
      and robotic group were 26.6 % and 16.2 %, respectively (p = 0.137). With a median
      follow up of 3 years, the local recurrence in the laparoscopic and robotic group
      was four (6.3 %) and two (2.7 %), respectively (p = 0.420). The 3-year overall
      survival rate for laparoscopic and robotic group was 92.1 and 90.0 %,
      respectively (p = 0.803). The 3-year disease-free survival was also comparable,
      78.8 % (laparoscopic) versus 77.7 % (robotic) (p = 0.390). CONCLUSION: With a
      median follow up of 3 years, robotic surgery for mid and low rectal cancer was
      associated with oncological outcomes comparable to laparoscopic surgery.

PMID- 23948970
TI  - Exposure to multi-walled carbon nanotubes results in aggravation of airway
      inflammation and remodeling and in increased production of epithelium-derived
      innate cytokines in a mouse model of asthma.
AB  - With the development of nanotechnologies, the potential adverse effects of
      nanomaterials such as multi-walled carbon nanotubes (MWCNT) on the respiratory
      tract of asthmatics are questioned. Furthermore, investigations are necessary to
      understand how these effects might arise. In the present study, we hypothesized
      that epithelium-derived innate cytokines that are considered as important
      promoting factors in allergy may contribute to an aggravating effect of MWCNT on
      asthma. We investigated in the mouse the effect of MWCNT on systemic immune
      response and airway inflammation and remodeling induced by the most frequent
      allergen so far associated with asthma, house dust mite (HDM), and we examined
      the production of the innate cytokines thymic stromal lymphopoietin (TSLP), IL
      25, IL-33, and GM-CSF. Mice exposed to HDM exhibited specific IgG1 in serum and
      inflammatory cell infiltration, and increased Th2 cytokine production, mucus
      hyperproduction, and collagen deposition in the airways when compared to naive
      animals. Levels of total IgG1 and HDM-specific IgG1, influx of macrophages,
      eosinophils and neutrophils, production of collagen, TGF-beta1, and mucus, as
      well as levels of IL-13, eotaxin, and TARC, were dose-dependently increased in
      mice exposed to HDM and MWCNT compared to HDM alone. These effects were
      associated with an increased production of TSLP, IL-25, IL-33, and GM-CSF in the
      airways. Our data demonstrate that MWCNT increase in a dose-dependent manner
      systemic immune response, as well as airway allergic inflammation and remodeling
      induced by HDM in the mouse. Our data suggest also a role for airway epithelium
      and innate cytokines in these effects. 

PMID- 23948969
TI  - Familial pancreatic cancer--status quo.
AB  - INTRODUCTION: Familial pancreatic cancer (FPC) is defined by families with at
      least two first-degree relatives with confirmed pancreatic ductal adenocarcinoma
      (PDAC) that do not fulfill the criteria of other inherited tumor syndromes with
      an increased risk for the development of PDAC, such as hereditary pancreatitis or
      hereditary breast and ovarian cancer. FPC is mostly autosomal dominant inherited
      and presents with a heterogeneous phenotype. Although the major gene defect has
      not yet been identified, some important germline mutations in the BRCA2-, PALB2-,
      and ATM-genes are causative in some FPC families. FPC SCREENING: It is suggested
      by experts to include high-risk individuals in a screening program with a
      multidisciplinary approach under research protocol conditions. However, neither
      biomarkers nor reliable imaging modalities for the detection of high-grade
      precursor lesions are yet available. Most screening programs are currently based
      on endoscopic ultrasound and magnetic resonance imaging, and first data
      demonstrated that precursor lesions (pancreatic intraepithelial neoplasia,
      intraductal papillary mucinous neoplasm) of PDAC can be identified. Timing and
      extent of surgery are still a matter of debate. SCOPE OF THE REVIEW: The present
      review focuses on the clinical phenotype of FPC, its histopathological
      characteristics, known underlying genetic changes, genetic counseling, and
      screening.

PMID- 23948971
TI  - CD62L as a therapeutic target in chronic lymphocytic leukemia.
AB  - PURPOSE: Despite advances in the treatment of chronic lymphocytic leukemia (CLL),
      the disease remains incurable with standard therapies and relapse is inevitable.
      A growing body of evidence indicates that alterations in the adhesion properties
      of neoplastic cells play a pivotal role in the development and progression of
      CLL. EXPERIMENTAL DESIGN: The expression of 71 cell surface molecules was
      examined on CLL peripheral blood mononuclear cells (PBMCs) over 3 weeks in
      culture. The most highly upregulated marker, CD62L, was examined further for
      expression on CD5(+)/CD19(+) CLL cells in vitro and in lymph node and bone marrow
      biopsies. The prosurvival role of CD62L was examined using a functional blocking
      antibody and therapeutic potential evaluated by comparison with current
      chemotherapy agents. RESULTS: Blocking CD62L resulted in apoptosis of CLL cells
      but not PBMCs from healthy donors suggesting a novel role for CD62L in CLL cell
      survival. The beneficial effect of coculturing CLL cells with bone marrow stromal
      cells or endothelial cells does not protect CLL cells from anti-CD62L-related
      toxicity. Moreover, combining fludarabine or mafosfamide with the anti-CD62L in
      vitro produced an additive effect both with and without stromal cells.
      CONCLUSION: This is the first reported data showing that blocking the activation
      and homing marker, CD62L, regulates CLL cell survival in vitro. These data also
      suggest that therapeutic antibodies against CD62L may provide additional clinical
      benefit to patients with CLL receiving current standard chemotherapy protocols.

PMID- 23948972
TI  - Identification of multiple mechanisms of resistance to vemurafenib in a patient
      with BRAFV600E-mutated cutaneous melanoma successfully rechallenged after
      progression.
AB  - PURPOSE: To investigate the mechanism(s) of resistance to the RAF-inhibitor
      vemurafenib, we conducted a comprehensive analysis of the genetic alterations
      occurring in metastatic lesions from a patient with a BRAF(V600E)-mutant
      cutaneous melanoma who, after a first response, underwent subsequent rechallenge
      with this drug. EXPERIMENTAL DESIGN: We obtained blood and tissue samples from a
      patient diagnosed with a BRAF(V600E)-mutant cutaneous melanoma that was treated
      with vemurafenib and achieved a near-complete response. At progression, he
      received additional lines of chemo/immunotherapy and was successfully
      rechallenged with vemurafenib. Exome and RNA sequencing were conducted on a
      pretreatment tumor and two subcutaneous resistant metastases, one that was
      present at baseline and previously responded to vemurafenib (PV1) and one that
      occurred de novo after reintroduction of the drug (PV2). A culture established
      from PV1 was also analyzed. RESULTS: We identified two NRAS-activating somatic
      mutations, Q61R and Q61K, affecting two main subpopulations in the metastasis PV1
      and a BRAF alternative splicing, involving exons 4-10, in the metastasis PV2.
      These alterations, known to confer resistance to RAF inhibitors, were tumor
      specific, mutually exclusive, and were not detected in pretreatment tumor
      samples. In addition, the oncogenic PIK3CA(H1047R) mutation was detected in a
      subpopulation of PV1, but this mutation did not seem to play a major role in
      vemurafenib resistance in this metastasis. CONCLUSIONS: This work describes the
      coexistence within the same patient of different molecular mechanisms of
      resistance to vemurafenib affecting different metastatic sites. These findings
      have direct implications for the clinical management of BRAF-mutant melanoma.

PMID- 23948973
TI  - Human breast cancer cells harboring a gatekeeper T798M mutation in HER2
      overexpress EGFR ligands and are sensitive to dual inhibition of EGFR and HER2.
AB  - PURPOSE: Mutations in receptor tyrosine kinase (RTK) genes can confer resistance
      to receptor-targeted therapies. A T798M mutation in the HER2 oncogene has been
      shown to confer resistance to the tyrosine kinase inhibitor (TKI) lapatinib. We
      studied the mechanisms of HER2-T798M-induced resistance to identify potential
      strategies to overcome that resistance. EXPERIMENTAL DESIGN: HER2-T798M was
      stably expressed in BT474 and MCF10A cells. Mutant cells and xenografts were
      evaluated for effects of the mutation on proliferation, signaling, and tumor
      growth after treatment with combinations of inhibitors targeting the
      EGFR/HER2/HER3/PI3K axis. RESULTS: A low 3% allelic frequency of the T798M mutant
      shifted 10-fold the IC50 of lapatinib. In mutant-expressing cells, lapatinib did
      not block basal phosphorylation of HER2, HER3, AKT, and ERK1/2. In vitro kinase
      assays showed increased autocatalytic activity of HER2-T798M. HER3 association
      with PI3K p85 was increased in mutant-expressing cells. BT474-T798M cells were
      also resistant to the HER2 antibody trastuzumab. These cells were sensitive to
      the pan-PI3K inhibitors BKM120 and XL147 and the irreversible HER2/EGFR TKI
      afatinib but not the MEK1/2 inhibitor CI-1040, suggesting continued dependence of
      the mutant cells on ErbB receptors and downstream PI3K signaling. BT474-T798M
      cells showed increased expression of the EGFR ligands EGF, TGFalpha,
      amphiregulin, and HB-EGF. Addition of the EGFR neutralizing antibody cetuximab or
      lapatinib restored trastuzumab sensitivity of BT474-T798M cells and xenografts,
      suggesting that increased EGFR ligand production was causally associated with
      drug resistance. CONCLUSIONS: Simultaneous blockade of HER2 and EGFR should be an
      effective treatment strategy against HER2 gene-amplified breast cancer cells
      harboring T798M mutant alleles.

PMID- 23948974
TI  - The integrin inhibitor cilengitide affects meningioma cell motility and invasion.
AB  - PURPOSE: Meningiomas are frequent intracranial or spinal neoplasms, which recur
      frequently and can show aggressive clinical behaviour. We elucidated the impact
      of the integrin inhibitor cilengitide on migration, proliferation, and
      radiosensitization of meningioma cells. EXPERIMENTAL DESIGN: We analyzed integrin
      expression in tissue microarrays of human meningiomas and the antimeningioma
      properties of cilengitide in cell cultures, subcutaneous and intracranial nude
      mouse models by measuring tumor volumes and survival times. RESULTS: alphavbeta5
      was the predominantly expressed integrin heterodimer in meningiomas, whereas
      alphavbeta3 was mainly detected in tumor blood vessels. Application of up to 100
      MUg/mL cilengitide resulted in only mildly reduced proliferation/survival of
      meningioma cell lines. Effects on cell survival could be enhanced by irradiation.
      One MUg/mL cilengitide was sufficient to significantly inhibit meningioma cell
      migration and invasion in vitro. A daily dosage of 75 mg/kg did neither affect
      tumor volumes nor overall survival (P = 0.813, log-rank test), but suppressed
      brain invasion in a significant fraction of treated animals. A combination of 75
      mg/kg cilengitide daily and irradiation (2 * 5 Gy) led to a 67% reduction of MRI
      estimated tumor volumes in the intracranial model (P < 0.01), whereas the
      corresponding reduction reached by irradiation alone was only 55% (P < 0.05).
      CONCLUSIONS: These data show that a monotherapy with cilengitide is not likely to
      achieve major responses in rapidly growing malignant meningiomas, although brain
      invasion may be reduced because of the strong antimigratory properties of the
      drug. The combination with radiotherapy warrants further attention.

PMID- 23948975
TI  - Differential response to neoadjuvant chemotherapy among 7 triple-negative breast
      cancer molecular subtypes.
AB  - PURPOSE: The clinical relevancy of the 7-subtype classification of triple
      negative breast cancer (TNBC) reported by Lehmann and colleagues is unknown. We
      investigated the clinical relevancy of TNBC heterogeneity by determining
      pathologic complete response (pCR) rates after neoadjuvant chemotherapy, based on
      TNBC subtypes. EXPERIMENTAL DESIGN: We revalidated the Lehmann and colleagues
      experiments using Affymetrix CEL files from public datasets. We applied these
      methods to 146 patients with TNBC with gene expression microarrays obtained from
      June 2000 to March 2010 at our institution. Of those, 130 had received standard
      neoadjuvant chemotherapy and had evaluable pathologic response data. We
      classified the TNBC samples by subtype and then correlated subtype and pCR status
      using Fisher exact test and a logistic regression model. We also assessed
      survival and compared the subtypes with PAM50 intrinsic subtypes and residual
      cancer burden (RCB) index. RESULTS: TNBC subtype and pCR status were
      significantly associated (P = 0.04379). The basal-like 1 (BL1) subtype had the
      highest pCR rate (52%); basal-like 2 (BL2) and luminal androgen receptor had the
      lowest (0% and 10%, respectively). TNBC subtype was an independent predictor of
      pCR status (P = 0.022) by a likelihood ratio test. The subtypes better predicted
      pCR status than did the PAM50 intrinsic subtypes (basal-like vs. non basal-like).
      CONCLUSIONS: Classifying TNBC by 7 subtypes predicts high versus low pCR rate. We
      confirm the clinical relevancy of the 7 subtypes of TNBC. We need to
      prospectively validate whether the pCR rate differences translate into long-term
      outcome differences. The 7-subtype classification may spur innovative
      personalized medicine strategies for patients with TNBC.

PMID- 23948976
TI  - MGMT-STP27 methylation status as predictive marker for response to PCV in
      anaplastic Oligodendrogliomas and Oligoastrocytomas. A report from EORTC study
      26951.
AB  - PURPOSE: The long-term follow-up results from the EORTC-26951 trial showed that
      the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy
      increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA).
      However, some patients appeared to benefit more from PCV treatment than others.
      EXPERIMENTAL DESIGN: We conducted genome-wide methylation profiling of 115
      samples included in the EORTC-26951 trial and extracted the CpG island
      hypermethylated phenotype (CIMP) and MGMT promoter methylation (MGMT-STP27)
      status. RESULTS: We first show that methylation profiling can be conducted on
      archival tissues with a performance that is similar to snap-frozen tissue
      samples. We then conducted methylation profiling on EORTC-26951 clinical trial
      samples. Univariate analysis indicated that CIMP+ or MGMT-STP27 methylated tumors
      had an improved survival compared with CIMP- and/or MGMT-STP27 unmethylated
      tumors [median overall survival (OS), 1.05 vs. 6.46 years and 1.06 vs. 3.8 years,
      both P < 0.0001 for CIMP and MGMT-STP27 status, respectively]. Multivariable
      analysis indicates that CIMP and MGMT-STP27 are significant prognostic factors
      for survival in presence of age, sex, performance score, and review diagnosis in
      the model. CIMP+ and MGMT-STP27 methylated tumors showed a clear benefit from
      adjuvant PCV chemotherapy: the median OS of CIMP+ samples in the RT and RT-PCV
      arms was 3.27 and 9.51 years, respectively (P = 0.0033); for MGMT-STP27
      methylated samples, it was 1.98 and 8.65 years. There was no such benefit for
      CIMP- or for MGMT-STP27 unmethylated tumors. MGMT-STP27 status remained
      significant in an interaction test (P = 0.003). Statistical analysis of
      microarray (SAM) identified 259 novel CpGs associated with treatment response.
      CONCLUSIONS: MGMT-STP27 may be used to guide treatment decisions in this tumor
      type.

PMID- 23948977
TI  - Association of cartilage defects, and other MRI findings with pain and function
      in individuals with mild-moderate radiographic hip osteoarthritis and controls.
AB  - OBJECTIVE: To evaluate the relationship of hip radiographic osteoarthritis (ROA)
      and MRI findings of cartilage lesions, labral tears, bone marrow edema-like
      lesions (BMELs) and subchondral cysts with self-reported and physical function.
      DESIGN: Eighty five subjects were classified as controls (n = 55, Kellgren
      Lawrence (KL) 0, 1) or having mild-moderate ROA (n = 30, KL 2, 3). T2 weighted
      MRI images at 3-T were graded for presence of cartilage lesions, labral tears,
      BMELs and subchondral cysts. Posterior wall sign, cross-over sign, center-edge
      angle and alpha angle were also recorded. Function was assessed using Hip
      dysfunction and Osteoarthritis Outcome Score (HOOS), Timed-Up and Go (TUG) test
      and Y-Balance Test (YBT). Analysis compared function between subjects with and
      without ROA and those with and without femoral or acetabular cartilage lesions,
      adjusted for age. Non-parametric correlations were used to assess the
      relationship between radiographic scores, MRI scores and function. RESULTS:
      Subjects with acetabular cartilage lesions had worse HOOS (Difference = 5-10%, P
      = 0.036-0.004), but not TUG or YBT, scores. Acetabular cartilage lesions, BMELs
      and subchondral cysts were associated with worse HOOS scores (rho = 0.23-0.37, P
      = 0.041-0.001). Differences in function between subjects with and without ROA or
      femoral cartilage lesions were not significant. Other radiologic findings were
      not associated with function. CONCLUSIONS: Acetabular cartilage defects, but not
      femoral cartilage defects or ROA, were associated with greater self-reported pain
      and disability. BMELs and subchondral cysts were related to greater hip related
      self-reported pain and disability. None of the radiographic or MRI features was
      related to physical function.

PMID- 23948978
TI  - Oxidative stress and status of antioxidant enzymes in children with Kashin-Beck
      disease.
AB  - OBJECTIVES: To clarify whether there is oxidative stress in Kashin-Beck disease
      (KBD) and if cartilage damage from reactive oxygen species (ROS) and oxidative
      stress mediate the chondral necrosis in articular cartilage of KBD. METHODS: We
      recruited 64 KBD patients, 46 healthy children from severely affected KBD
      regions, 81 healthy children from a non-severely affected KBD endemic regions,
      and 91 healthy control children from a non-KBD region. Ten patients with KBD from
      the non-severely affected KBD regions were included in the experiment. The 2,3
      DAN fluorescence technique was used to test selenium in the hair and blood. The
      biochemical techniques used to test the indicators of oxidative stress included
      thiobarbituric acid reactive substances (TBARS) levels, and antioxidant enzyme
      activities in serum samples. Histochemical staining was used to detect
      proteoglycans in cartilage sections. The 4-hydroxy-2-nonenal (4-HNE) and 8
      hydroxydeoxyguanisine (8-OHdG) were localized by immunohistochemistry. RESULTS:
      The levels of TBARS in serum were significantly increased in KBD children. The
      levels of antioxidants in serum were significantly higher in both KBD and normal
      children from KBD regions than in the normal children from non-KBD regions. The
      percentage of chondrocytes staining for 4-HNE and 8-OHdG in KBD patients was
      significantly higher than in controls. Staining for 4-HNE and 8-OHdG in KBD
      patients was prominent in all zones of articular cartilage, especially in the
      necrotic chondrocytes of the deep zone. CONCLUSION: KBD is an oxidative stress
      related disease, and the oxidative stress in cartilage contributes to the
      pathology of cartilage damage in KBD.

PMID- 23948979
TI  - What proportion of people with hip and knee osteoarthritis meet physical activity
      guidelines? A systematic review and meta-analysis.
AB  - OBJECTIVE: To determine the proportion of people with hip and knee osteoarthritis
      that meet physical activity guidelines recommended for adults and older adults.
      METHOD: Systematic review with meta-analysis of studies measuring physical
      activity of participants with hip and knee osteoarthritis using an activity
      monitor. Physical activity levels were calculated using the mean average [95%
      confidence interval (CI)] weighted according to sample size. Meta-analyses
      determined the proportion of people meeting physical activity guidelines and
      recommendations of (1) >=150 min per week of moderate to vigorous physical
      activity (MVPA) in bouts of >=10 min; (2) >=150 min per week of MVPA in absence
      of bouts; (3) >=10,000 steps per day and >=7000 steps per day. The Grades of
      Research, Assessment, Development and Evaluation (GRADE) approach was used to
      determine the quality of the evidence. RESULTS: For knee osteoarthritis, 21
      studies involving 3266 participants averaged 50 min per week (95% CI = 46, 55) of
      MVPA when measured in bouts of >=10 min, 131 min per week (95% CI = 125, 137) of
      MVPA, and 7753 daily steps (95% CI = 7582, 7924). Proportion meta-analyses
      provided high quality evidence that 13% (95% CI = 7, 20) completed >=150 min per
      week of MVPA in bouts of >=10 min, low quality evidence that 41% (95% CI = 23,
      61) completed >=150 min per week of MVPA in absence of bouts, moderate quality
      evidence that 19% (95% CI = 8, 33) completed >=10,000 steps per day, and low
      quality evidence that 48% (95% CI = 31, 65) completed >=7000 steps per day. For
      hip osteoarthritis, 11 studies involving 325 participants averaged 160 min per
      week (95% CI = 114, 216) of MVPA when measured in bouts of >=10 min, 189 min per
      week (95% CI = 166, 212) of MVPA, and 8174 daily steps (95% CI = 7670, 8678).
      Proportion meta-analyses provided low quality evidence that 58% (95% CI = 18, 92)
      completed >=150 min per week of MVPA in absence of bouts, low quality evidence
      that 30% (95% CI = 13, 50) completed >=10,000 steps per day, and low quality
      evidence that 60% (95% CI = 47, 73) completed >=7000 steps per day. CONCLUSION: A
      small to moderate proportion of people with knee and hip osteoarthritis met
      physical activity guidelines and recommended daily steps. Future research should
      establish the effects of increasing physical activity in this population to meet
      the current physical activity guidelines.

PMID- 23948980
TI  - Varus thrust and knee frontal plane dynamic motion in persons with knee
      osteoarthritis.
AB  - OBJECTIVE: Varus thrust visualized during walking is associated with a greater
      medial knee load and an increased risk of medial knee osteoarthritis (OA)
      progression. Little is known about how varus thrust presence determined by visual
      observation relates to quantitative gait kinematic data. We hypothesized that
      varus thrust presence is associated with greater knee frontal plane dynamic
      movement during the stance phase of gait. METHODS: Participants had knee OA in at
      least one knee. Trained examiners assessed participants for varus thrust presence
      during ambulation. Frontal plane knee motion during ambulation was captured using
      external passive reflective markers and an 8-camera motion analysis system. To
      examine the cross-sectional relationship between varus thrust and frontal plane
      knee motion, we used multivariable regression models with the quantitative motion
      measures as dependent variables and varus thrust (present/absent) as predictor;
      models were adjusted for age, gender, body mass index (BMI), gait speed, and knee
      static alignment. RESULTS: 236 persons [mean BMI: 28.5 kg/m(2) (standard
      deviation (SD) 5.5), mean age: 64.9 years (SD 10.4), 75.8% women] contributing
      440 knees comprised the study sample. 82 knees (18.6%) had definite varus thrust.
      Knees with varus thrust had greater peak varus angle and greater peak varus
      angular velocity during stance than knees without varus thrust (mean differences
      0.90 degrees  and 6.65 degrees /s, respectively). These patterns remained
      significant after adjusting for age, gender, BMI, gait speed, and knee static
      alignment. CONCLUSION: Visualized varus thrust during walking was associated with
      a greater peak knee varus angular velocity and a greater peak knee varus angle
      during stance phase of gait.

PMID- 23948981
TI  - Clinical and biomechanical performance of patients with failed rotator cuff
      repair.
AB  - PURPOSE: The purpose of the study was clinical and advanced biomechanical
      evaluation of shoulder function with respect to rotator cuff (RC) integrity
      following repair. METHODS: This was a retrospective study of 111 cases with solid
      single row rotator cuff repair and a minimal one-year follow-up. The RC repair
      was performed as an open procedure in 42 patients, arthroscopically assisted in
      34 and fully arthroscopic in 48 cases. Evaluation protocol included ultrasound
      evaluation of the RC integrity, clinical evaluation using shoulder scores and
      advanced biomechanical evaluation (isometric and the isokinetic strength
      testing). RESULTS: Ultrasound evaluation revealed complete retear in 16%, partial
      retear in 10% and intact repair in 74% of the cases. Isometric testing of flexion
      and abduction had shown that shoulders with complete retear were weaker by 45%
      compared to those with full tendon healing. Isokinetic testing revealed 29-43%
      deficits in peak external rotation torque comparing complete retear vs. normal
      healing. Patients' ability to generate shoulder power and withstand a load proved
      to be lower in circumstances of a complete lack of healing (40-43% and 34-55%,
      respectively). Partial retears did not have a negative impact on the
      biomechanical properties of shoulders. Surprisingly, there were no significant
      differences in the shoulder scores related to the quality of healing. In terms of
      patient satisfaction the results were good and the patients declared themselves
      better in all cases, no matter what quality of healing had been recorded
      ultimately. CONCLUSIONS: According to the results of this research rotator cuff
      integrity after open or arthroscopic repair does not seem to affect clinical
      scores. Recurrent tears may result in lower muscle performance in terms of active
      motion, strength and endurance. Advanced shoulder testing may be essential in
      assessing the patients' ability to return to sports or heavy labour.

PMID- 23948982
TI  - Magnetic resonance imaging is not suitable for interpretation of meniscal status
      ten years after arthroscopic repair.
AB  - PURPOSE: The purpose of this study was to assess the MRI features of the all
      inside repaired meniscus in the long-term. METHODS: Among 27 consecutive all
      inside arthroscopic meniscal repairs, 23 patients aged 25 +/- 5 years at the time
      of surgery were reviewed at a median follow-up of 10 +/- 1 years. Retrospective
      clinical examinations and imaging assessments using a 1.5-T MRI after all-inside
      arthroscopic meniscal repair were conducted. RESULTS: At follow-up, Lysholm and
      IKDC averaged 89 +/- 11 and 95 +/- 8, respectively. MRI examinations revealed no
      meniscal signal alteration in three patients (13%), a vertical signal located in
      the previously torn area in seven (30%), a horizontal grade 3 in nine (39%), and
      a complex tear (grade 4) in four (17.5%). There were no differences between
      medial and lateral menisci (p = 0.15), stable and stabilised knees (p = 0.56).
      CONCLUSIONS: Several abnormal vertical and/or horizontal hypersignals are still
      present on MRI examination ten years after arthroscopic all-inside meniscal
      repair. The appearance of early signs of osteoarthritis is rare, suggesting a
      chondroprotective effect of the repaired meniscus.

PMID- 23948984
TI  - Osteoid osteoma of the shoulder and elbow: from diagnosis to minimally invasive
      removal.
AB  - PURPOSE: Musculoskeletal tumours are rare in the daily practice of an orthopaedic
      surgeon or even a shoulder and elbow specialist. Patient complaints are often
      related to secondary changes to the underlying disease making the correct
      diagnosis challenging. The goal of this study is to identify key symptoms and
      findings which should give rise to suspicion of an osteoid osteoma. METHODS: This
      retrospective study analyses the diagnostic pathway, surgical treatment and
      clinical outcome of six patients who underwent resection of an osteoid osteoma of
      the shoulder or elbow joint. RESULTS: Average follow-up was 24 months (range 16
      36 months). The neoplasm was often associated with synovitis mimicking a frozen
      joint causing marked delay in tumour identification. Misdiagnosis led to surgery
      without addressing the tumour in two cases, making further surgical intervention
      necessary. Once the tumour was identified and removed the pain resolved rapidly.
      CONCLUSIONS: In cases of chronic shoulder or elbow pain without an adequate
      clinical history an underlying cause including rarities such as an osteoid
      osteoma or other musculoskeletal tumours should be taken into consideration.
      Particularly in young patients, a magnetic resonance imaging (MRI)-proven hot
      spot of unknown origin should prompt a computed tomography examination to further
      clarify the source of pain and stiffness. LEVEL OF EVIDENCE: IV, case series.

PMID- 23948985
TI  - Plasmonic nanocomposite thin film enabled fiber optic sensors for simultaneous
      gas and temperature sensing at extreme temperatures.
AB  - Embedded sensors capable of operation in extreme environments including high
      temperatures, high pressures, and highly reducing, oxidizing and/or corrosive
      environments can make a significant impact on enhanced efficiencies and reduced
      greenhouse gas emissions of current and future fossil-based power generation
      systems. Relevant technologies can also be leveraged in a wide range of other
      applications with similar needs including nuclear power generation, industrial
      process monitoring and control, and aviation/aerospace. Here we describe a novel
      approach to embedded sensing under extreme temperature conditions by integration
      of Au-nanoparticle based plasmonic nanocomposite thin films with optical fibers
      in an evanescent wave absorption spectroscopy configuration. Such sensors can
      potentially enable simultaneous temperature and gas sensing at temperatures
      approaching 900-1000  degrees C in a manner compatible with embedded and
      distributed sensing approaches. The approach is demonstrated using the Au/SiO2
      system deposited on silica-based optical fibers. Stability of optical fibers
      under relevant high temperature conditions and interactions with changing ambient
      gas atmospheres is an area requiring additional investigation and development but
      the simplicity of the sensor design makes it potentially cost-effective and may
      offer a potential for widespread deployment. 

PMID- 23948983
TI  - Role of mesenchymal stem cells in bone regeneration and fracture repair: a
      review.
AB  - Mesenchymal stem cells (MSCs) are non-haematopoietic stromal stem cells that have
      many sources, such as bone marrow, periosteum, vessel walls, adipose, muscle,
      tendon, peripheral circulation, umbilical cord blood, skin and dental tissues.
      They are capable of self-replication and of differentiating into, and
      contributing to the regeneration of, mesenchymal tissues, such as bone,
      cartilage, ligament, tendon, muscle and adipose tissue. The homing of MSCs may
      play an important role in the repair of bone fractures. As a composite material,
      the formation and growth of bone tissue is a complex process, including
      molecular, cell and biochemical metabolic changes. The recruitment of factors
      with an adequate number of MSCs and the micro-environment around the fracture are
      effective for fracture repair. Several studies have investigated the functional
      expression of various chemokine receptors, trophic factors and adhesion molecules
      in human MSCs. Many external factors affect MSC homing. MSCs have been used as
      seed cells in building tissue-engineered bone grafts. Scaffolds seeded with MSCs
      are most often used in tissue engineering and include biotic and abiotic
      materials. This knowledge provides a platform for the development of novel
      therapies for bone regeneration with endogenous MSCs. 

PMID- 23948986
TI  - Triple therapy for anti-vascular endothelial growth factor nonresponders in
      neovascular age-related macular degeneration: impact of different photodynamic
      therapy parameters.
AB  - PURPOSE: To evaluate the safety and exploratory efficacy of triple therapy (TT)
      with single-session intravitreal ranibizumab, modified juxtascleral
      triamcinolone, and photodynamic therapy (PDT) in exudative age-related macular
      degeneration non-responder to anti-vascular endothelial growth factor. METHODS:
      Thirty consecutive eyes were included. The first 10 eyes (cohort 1) enrolled
      received same-day TT with reduced-fluence/reduced-irradiance PDT, 10 eyes (cohort
      2) received same-day TT with reduced-fluence/standard irradiance PDT, the last 10
      eyes (cohort 3) received same-day TT with standard fluence/standard irradiance
      PDT. RESULTS: All patients completed the 6-month follow-up. Mean best corrected
      visual acuity (BCVA) at baseline was 1.1 (cohort 1), 0.9 (cohort 2) and 1.1
      (cohort 3) logMAR. After 6 months, mean BCVA change was -0.15 (not significant), 
      0.13 (not significant) and 0.29 (p < 0.05) logMAR, respectively. Among eyes
      treated with standard fluence/standard irradiance PDT, 2 showed choroidal
      ischemia. CONCLUSIONS: The combination of modified juxtascleral triamcinolone,
      reduced-fluence PDT, and ranibizumab appears as a safe treatment option.

PMID- 23948987
TI  - Impact of falls and fear of falling on health-related quality of life in patients
      with Parkinson's disease.
AB  - Postural instability, recurrent falls and fear of falling are common in advanced
      Parkinson's disease (PD). We examined the impact of fall frequency, fear of
      falling, balance confidence and objectively measured balance impairment (using
      Tinetti's Mobility Index) on health-related quality of life (HrQoL) in PD. In 74
      subjects HrQoL was assessed using the 39-item Parkinson's disease Quality of Life
      Questionnaire [PDQ-39]. Patients were interviewed using a validated falls
      questionnaire, addressing fall history, consequences of falls and fear of
      falling. Neurological examination included Hoehn and Yahr scale, the Unified
      Parkinson's disease Rating Scale and Tinetti's Mobility Index. Disease severity,
      age and gender explained 43% of the differences in HrQoL across patients (R2 =
      0.43). The combination of these factors and each of the factors fear of falling,
      balance confidence and fall frequency lead to 55%, 50% and 45% of explained
      variation, respectively. The standardised regression coefficients of these risk
      factors were 0.34 (fear of falling), 0.28 (balance confidence) and 0.13 (fall
      frequency). This suggests that fear of falling is a more important determinant of
      HrQoL than actual falling. These results emphasise the importance of addressing
      fear of falling in the clinical management of PD, and the need for development of
      strategies to reduce fear of falling in intervention programs. 

PMID- 23948988
TI  - The role of basal ganglia in language production: evidence from Parkinson's
      disease.
AB  - According to the dominant view in the literature, basal ganglia do not play a
      direct role in language but are involved in cognitive control required by
      linguistic and non-linguistic processing. In Parkinson's disease, basal ganglia
      impairment leads to motor symptoms and language deficits; those affecting the
      production of verbs have been frequently explored. According to a controversial
      theory, basal ganglia play a specific role in the conjugation of regular verbs as
      compared to irregular verbs. We report the results of 15 patients with
      Parkinson's disease in experimental conjugation tasks. They performed below
      healthy controls but their performance did not differ for regular and irregular
      verbs. These results confirm that basal ganglia are involved in language
      processing but do not play a specific role in verb production. 

PMID- 23948989
TI  - Levodopa in the treatment of Parkinson's disease: current status and new
      developments.
AB  - Levodopa, a dopamine precursor, is an effective and well-tolerated dopamine
      replacement agent used to treat Parkinson's disease (PD). Oral levodopa has been
      widely used for over 40 years, often in combination with a dopa-decarboxylase
      inhibitor (DDCI), which reduces many treatment complications, extending its half
      life and increasing levodopa availability to the brain. Entacapone, a catechol-O
      methyltransferase inhibitor, can also be used to improve the bioavailability of
      levodopa, especially when used in conjunction with a DDCI. During early-stage PD,
      treatment will depend on the severity of symptoms; if greater symptomatic effect
      is required then levodopa or dopamine agonists are usually the drugs of choice.
      The ability to remain employable or physically active is an important goal in
      younger patients, therefore, in some instances levodopa initiation should be
      considered early on, either as a monotherapy or in combination with other drugs.
      The clinical use of levodopa may eventually be limited by the development of
      various treatment-related complications, including response fluctuations,
      dyskinesia and psychiatric problems. Motor complications are related to the
      intermittent delivery of dopamine-replacing drugs to the brain. Triple
      combination of levodopa/carbidopa/entacapone available in a single tablet in
      multiple levodopa dose strengths offers flexibility and helps control response
      fluctuations. Recent developments in treatment with levodopa try to obtain
      continuous delivery with levodopa and include duodenal infusion of a
      levodopa/carbidopa, transdermal levodopa patch, and oral pro-levodopa. Levodopa
      remains the most potent dopaminergic therapy for PD. 

PMID- 23948990
TI  - Role of serum cholesterol in Parkinson's disease: a meta-analysis of evidence.
AB  - BACKGROUND: Results from several epidemiological studies found a potential role
      of cholesterol metabolism in Parkinson's disease (PD) pathogenesis. Further
      several studies assessed relation between dietary intake of cholesterol and risk
      of PD, although these studies showed varied results but give a clue of
      association between serum cholesterol and PD. OBJECTIVE: We therefore examined
      the association between serum cholesterol and risk of PD. METHODS: PubMed
      database and bibliographies of retrieved articles were searched for observational
      studies (published up to January 2013) investigating the relationship between
      serum cholesterol and PD. Pooled risk ratio (RR) was calculated using random
      effects model. Subgroup, sensitivity analysis and publication bias were also
      done. RESULTS: Eight relevant studies were identified, consisting of 4 each case
      control and cohort studies involving a total of 246,112 subjects including 5,488
      PD cases. Because of significant heterogeneity (P(heterogeneity) < 0.001, I2 =
      70.34%) was observed, a random-effects model was chosen over a fixed-effects
      model. A combined analysis of 8 studies found no significant association between
      serum cholesterol and risk of PD (RR 0.87, 95% CI 0.67-1.13; p = 0.41).
      CONCLUSIONS: We observed no probable association between serum cholesterol and
      risk of PD.

PMID- 23948991
TI  - Increased expression of ABCA8 in multiple system atrophy brain is associated with
      changes in pathogenic proteins.
AB  - BACKGROUND: Multiple system atrophy (MSA) is a fatal neurodegenerative disease of
      unknown aetiology characterised by the accumulation of insoluble alpha-synuclein
      (alpha-syn) aggregates in the cytoplasm of myelin-producing oligodendrocytes.
      Dysfunction of the lipid-rich myelin membrane may precede alpha-syn pathology in
      MSA pathogenesis. ATP-binding cassette transporter A8 (ABCA8) is a little-studied
      lipid transporter, which has recently been found to be highly expressed in
      oligodendrocyte-rich white matter regions of the human brain. ABCA8 expression
      promotes sphingomyelin production in oligodendrocytes in vitro, suggesting a role
      in myelin formation and maintenance. OBJECTIVE: We hypothesise that aberrant
      ABCA8 expression in oligodendrocytes plays a role in the early pathogenesis of
      MSA by impacting myelin stability and regulation of alpha-syn and p25alpha.
      METHODS: We measured the expression of ABCA8, alpha-syn and p25alpha in MSA
      brains in disease-affected grey matter (GM, putamen and cerebellum), disease
      affected white matter (WM, under the motor cortex) and an unaffected brain region
      (visual cortex). We transfected human oligodendrocytes with ABCA8 and assessed
      its impact on alpha-syn and p25alpha expression. RESULTS: ABCA8 expression was
      significantly increased in the disease-affected GM and WM with no significant
      change in the unaffected brain region. alpha-syn and p25alpha expression were
      significantly increased in the disease-affected WM and GM respectively.
      Overexpression of ABCA8 in oligodendrocytes caused significant increases in both
      alpha-syn and p25alpha expression. CONCLUSIONS: These data suggest a direct
      relationship between the levels of ABCA8 and the ectopic expression of alpha-syn
      and increased expression of p25alpha. As these data reflect results found in MSA,
      we hypothesise that increased ABCA8 may precipitate MSA pathology.

PMID- 23948992
TI  - Daytime sleepiness is associated with falls in Parkinson's disease.
AB  - Falls are frequent in Parkinson's disease (PD), and may be influenced by daytime
      sleepiness. We reviewed the records of 120 men with PD. Mean Epworth Sleepiness
      Scale (ESS) values were significantly different between non-fallers and fallers
      (6.0 vs. 9.7, p < 0.01). In multivariate analysis, ESS remained significantly
      associated with falls (OR 1.2, 95% CI 1.1-1.4, p = 0.02), along with cognitive
      impairment (OR 4.4 95% CI 1.0-18.7, p = 0.04) and postural instability/gait
      dysfunction (OR 1.6 95% CI 1.0-2.4, p = 0.03) in non-depressed patients. In
      conclusion, non-depressed PD patients are 20% more likely to fall for every one
      unit increase in the ESS measure of sleepiness. 

PMID- 23948993
TI  - Objective motion sensor assessment highly correlated with scores of global
      levodopa-induced dyskinesia in Parkinson's disease.
AB  - BACKGROUND: Chronic use of medication for treating Parkinson's disease (PD) can
      give rise to peak-dose dyskinesia. Adjustments in medication often sacrifice
      control of motor symptoms, and thus balancing this trade-off poses a significant
      challenge for disease management. OBJECTIVE: To determine whether a wrist-worn
      motion sensor unit could be used to ascertain global dyskinesia severity over a
      levodopa dose cycle and to develop a severity scoring algorithm highly correlated
      with clinician ratings. METHODS: Fifteen individuals with PD were instrumented
      with a wrist-worn motion sensor unit, and data were collected with arms in
      resting and extended positions once every hour for three hours after taking a
      levodopa dose. Two neurologists blinded to treatment status viewed subject videos
      and rated global and upper extremity dyskinesia severity based on the modified
      Abnormal Involuntary Movement Scale (mAIMS). Linear regression models were
      developed using kinematic features extracted from motion sensor data and
      extremity, global, or combined (average of extremity and global) mAIMS scores.
      RESULTS: Dyskinesia occurring during a levodopa dose cycle was successfully
      measured using a wrist-worn sensor. The logarithm of the power spectrum area
      between 0.3-3 Hz and the combined clinician scores resulted in the best model
      performance, with a correlation coefficient between clinician and model scores of
      0.81 and root mean square error of 0.55, both averaged across the arms resting
      and extended postures. CONCLUSIONS: One sensor unit worn on either hand can
      effectively predict global dyskinesia severity during the arms resting or
      extended positions.

PMID- 23948995
TI  - Reduced striatal dopamine synthesis capacity is associated with symptoms of
      depression in patients with de novo unmedicated Parkinson's disease.
AB  - Previous studies have suggested that impaired striatal dopamine function might be
      independently related to depression in patients with Parkinson's disease (PD),
      but the results are not uniform. In this study, we investigated de novo
      unmedicated and medicated PD patients with more advanced disease using 18F
      fluorodopa-PET. In unmedicated de novo patients, but not in medicated patients,
      higher depression scores were associated with lower striatal 18F-fluorodopa
      uptake. These results indicate that impaired striatal dopaminergic function in PD
      is related to depressive symptoms and that these effects can be observed in de
      novo patients without the confounding effects of advanced neurodegeneration and
      medications. 

PMID- 23948996
TI  - Locomotor velocity and striatal adaptive gene expression changes of the direct
      and indirect pathways in Parkinsonian rats.
AB  - BACKGROUND: In Parkinson's disease (PD), bradykinesia, or slowness of movement,
      only appears after a large striatal dopamine depletion. Compensatory mechanisms
      probably play a role in this delayed appearance of symptoms. OBJECTIVE: Our
      hypothesis is that the striatal direct and indirect pathways participate in these
      compensatory mechanisms. METHODS: We used the unilateral 6-hydroxydopamine (6
      OHDA) rat model of PD and control animals. Four weeks after the lesion, the
      spontaneous locomotor activity of the rats was measured and then the animals were
      killed and their brain extracted. We quantified the mRNA expression of markers of
      the striatal direct and indirect pathways as well as the nigral expression of
      dopamine transporter (DAT) and tyrosine hydroxylase (TH) mRNA. We also carried
      out an immunohistochemistry for the striatal TH protein expression. RESULTS: As
      expected, the unilateral 6-OHDA rats presented a tendency to an ipsilateral head
      turning and a low locomotor velocity. In 6-OHDA rats only, we observed a
      significant and positive correlation between locomotor velocity and both D1-class
      dopamine receptor (D1R) (direct pathway) and enkephalin (ENK) (indirect pathway)
      mRNA in the lesioned striatum, as well as between D1R and ENK mRNA. CONCLUSIONS:
      Our results demonstrate a strong relationship between both direct and indirect
      pathways and spontaneous locomotor activity in the parkinsonian rat model. We
      suggest a synergy between both pathways which could play a role in compensatory
      mechanisms and may contribute to the delayed appearance of bradykinesia in PD.

PMID- 23948994
TI  - Review: electrophysiology of basal ganglia and cortex in models of Parkinson
      disease.
AB  - Incomplete understanding of the systems-level pathophysiology of Parkinson
      Disease (PD) remains a significant barrier to improving its treatment.
      Substantial progress has been made, however, due to the availability of
      neurotoxins that selectively target monoaminergic (in particular, dopaminergic)
      neurons. This review discusses the in vivo electrophysiology of basal ganglia
      (BG), thalamic, and cortical regions after dopamine-depleting lesions. These
      include firing rate changes, neuronal burst-firing, neuronal oscillations, and
      neuronal synchrony that result from a combination of local microanatomic changes
      and network-level interactions. While much is known of the clinical and
      electrophysiological phenomenology of dopamine loss, a critical gap in our
      conception of PD pathophysiology is the link between them. We discuss potential
      mechanisms by which these systems-level electrophysiological changes may emerge,
      as well as how they may relate to clinical parkinsonism. Proposals for an updated
      understanding of BG function are reviewed, with an emphasis on how emerging
      frameworks will guide future research into the pathophysiology and treatment of
      PD. 

PMID- 23948997
TI  - Feasibility study of alternate-day S-1 as adjuvant chemotherapy for gastric
      cancer: a randomized controlled trial.
AB  - BACKGROUND: The Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer established
      oral S-1 administration for 1 year as the standard postoperative adjuvant
      chemotherapy for gastric cancer in Japan. We conducted a multicenter cooperative
      prospective study comparing daily and alternate-day S-1 administration as
      postoperative adjuvant therapy for gastric cancer. METHODS: Patients with Stage
      II or III gastric cancer who underwent curative surgery were randomly assigned to
      receive standard daily S-1 administration [group A: 80-120 mg/day S-1 depending
      on body surface area (BSA); days 1-28 every 6 weeks for 1 year] or alternate-day
      administration (group B: 80-120 mg/day S-1 depending on BSA; alternate days for
      15 months). Treatment completion rate was the primary endpoint, and relative dose
      intensity and safety, overall survival, and relapse-free survival (RFS) were
      secondary endpoints. RESULTS: Seventy-three patients were enrolled. The treatment
      completion rate was 72.2 % in group A and 91.8 % in group B; the relative dose
      intensity was 67.5 % in group A and 81.2 % in group B; and compliance was better
      in group B. Digestive system adverse effects were less frequent in group B than
      in group A. Median follow-up time was 2.8 years; 3-year survival rate was 69.6 %
      in group A and 87.3 % in group B; and 3-year RFS rate was 76.4 % in group A and
      73.1 % in group B. CONCLUSIONS: Our data show improved compliance and fewer
      adverse effects with alternate-day S-1 administration, which appears to be a more
      sustainable option for adjuvant chemotherapy for Stage II or III gastric cancer.

PMID- 23948998
TI  - Lapatinib sensitivities of two novel trastuzumab-resistant HER2 gene-amplified
      gastric cancer cell lines.
AB  - BACKGROUND: Trastuzumab (Tmab) resistance is a major clinical problem to be
      resolved in patients with HER2-positive gastric cancers. However, in contrast to
      the situation for HER2-positive breast cancer lines, the Tmab-resistant gastric
      cancer preclinical models that are needed to develop a new therapy to overcome
      this problem are not yet available. METHODS: We developed three new cell lines
      from HER2 gene-amplified gastric cancer cell lines (GLM-1, GLM-4, NCI N-87) by a
      new in vivo selection method consisting of the repeated culture of small residual
      peritoneal metastasis but not subcutaneous tumor after Tmab treatment. We then
      evaluated the anti-tumor efficacy of lapatinib for these Tmab-resistant cells.
      RESULTS: We successfully isolated two Tmab-resistant cell lines (GLM1-HerR2(3),
      GLM4-HerR2) among the three tested cell lines. These resistant cells differed
      from the parental cells in their flat morphology and rapid growth in vitro, but
      HER2, P95HER2 expression, and Tmab binding were essentially the same for the
      parental and resistant cells. MUC4 expression was up- or downregulated depending
      on the cell line. These resistant cells were still sensitive to lapatinib,
      similar to the parental cells, in vitro. This growth inhibition of the Tmab
      resistant cells by lapatinib was due to both G1 cell-cycle arrest and apoptosis
      induction via effective blockade of the PI3K/Akt and MAPK pathways. A preclinical
      study confirmed that the Tmab-resistant tumors are significantly susceptible to
      lapatinib. CONCLUSION: These results suggest that lapatinib has antitumor
      activity against the Tmab-resistant gastric cancer cell lines, and that these
      cell lines are useful for understanding the mechanism of Tmab resistance and for
      developing a new molecular therapy for Tmab-resistant HER2-positive gastric
      cancers.

PMID- 23948999
TI  - Decoy-state quantum key distribution with biased basis choice.
AB  - We propose a quantum key distribution scheme that combines a biased basis choice
      with the decoy-state method. In this scheme, Alice sends all signal states in the
      Z basis and decoy states in the X and Z basis with certain probabilities, and Bob
      measures received pulses with optimal basis choice. This scheme simplifies the
      system and reduces the random number consumption. From the simulation result
      taking into account of statistical fluctuations, we find that in a typical
      experimental setup, the proposed scheme can increase the key rate by at least 45%
      comparing to the standard decoy-state scheme. In the postprocessing, we also
      apply a rigorous method to upper bound the phase error rate of the single-photon
      components of signal states. 

PMID- 23949000
TI  - A longitudinal study of the teacch program in different settings: the potential
      benefits of low intensity intervention in preschool children with autism spectrum
      disorder.
AB  - We conducted a longitudinal study of 30 preschool children with autism spectrum
      disorders (ASDs) to evaluate the potential benefits of the Treatment and
      Education of Autistic and related Communication Handicapped Children (TEACCH).
      Fifteen children following a low intensity TEACCH program were assessed four
      times for autism severity, adaptive functioning, language skills, maladaptive
      behaviors and parental stress and compared with a control group of 15 children
      following a non-specific approach. Findings suggest that a low intensity home and
      school TEACCH program may provide benefits for children with ASD by reducing
      autistic symptoms and maladaptive behaviors. Furthermore, a decrease in parental
      stress indicates that parents' involvement in the rehabilitation program is a
      crucial factor and contributes greatly to treatment efficacy. 

PMID- 23949001
TI  - Nitrate anion templated assembly of a [2]rotaxane for selective nitrate
      recognition in aqueous solvent mixtures.
AB  - The first nitrate anion templated assembly of an interlocked molecular
      architecture is demonstrated through the preparation of a [2]rotaxane. Removal of
      the discrete nitrate anion template from the [2]rotaxane reveals an interlocked
      host system capable of strong and selective recognition of nitrate, in aqueous
      organic solvent mixtures, over a range of more basic mono-charged oxoanions. 

PMID- 23949002
TI  - Genome duplication in early vertebrates: insights from agnathan cytogenetics.
AB  - Agnathans represent a remnant of a primitive offshoot of the vertebrates, and the
      long evolutionary separation between their 2 living groups, namely hagfishes and
      lampreys, could explain profound biological differences, also in karyotypes and
      genome sizes. Here, cytogenetic studies available on these vertebrates were
      summarized and data discussed with reference to the recently demonstrated
      monophyly of this group and to the 2 events of whole genome duplication (1R and
      2R) characterizing the evolution of vertebrates. The comparison of cytogenetic
      data and phylogenetic relationships among agnathans and gnathostomes seems to
      support the hypothesis that 1R and 2R occurred before the evolutionary divergence
      between jawless and jawed vertebrates.

PMID- 23949003
TI  - Adsorption of the organic salt TAB(HCl)4 on Cu(111) studied using STM and XPS.
AB  - Sublimation of Tetra-Amino Benzene (TAB) in its tetrahydrochlorinated form onto
      Cu(111) leads to the formation of long range ordered structures consisting of TAB
      molecules with partially protonated amino groups interspersed with Cl species. 

PMID- 23949004
TI  - Bacterial toxins fuel disease progression in cutaneous T-cell lymphoma.
AB  - In patients with cutaneous T-cell lymphoma (CTCL) bacterial infections constitute
      a major clinical problem caused by compromised skin barrier and a progressive
      immunodeficiency. Indeed, the majority of patients with advanced disease die from
      infections with bacteria, e.g., Staphylococcus aureus. Bacterial toxins such as
      staphylococcal enterotoxins (SE) have long been suspected to be involved in the
      pathogenesis in CTCL. Here, we review links between bacterial infections and CTCL
      with focus on earlier studies addressing a direct role of SE on malignant T cells
      and recent data indicating novel indirect mechanisms involving SE- and cytokine
      driven cross-talk between malignant- and non-malignant T cells. 

PMID- 23949005
TI  - Deletion and gene expression analyses define the paxilline biosynthetic gene
      cluster in Penicillium paxilli.
AB  - The indole-diterpene paxilline is an abundant secondary metabolite synthesized by
      Penicillium paxilli. In total, 21 genes have been identified at the PAX locus of
      which six have been previously confirmed to have a functional role in paxilline
      biosynthesis. A combination of bioinformatics, gene expression and targeted gene
      replacement analyses were used to define the boundaries of the PAX gene cluster.
      Targeted gene replacement identified seven genes, paxG, paxA, paxM, paxB, paxC,
      paxP and paxQ that were all required for paxilline production, with one
      additional gene, paxD, required for regular prenylation of the indole ring post
      paxilline synthesis. The two putative transcription factors, PP104 and PP105,
      were not co-regulated with the pax genes and based on targeted gene replacement,
      including the double knockout, did not have a role in paxilline production. The
      relationship of indole dimethylallyl transferases involved in prenylation of
      indole-diterpenes such as paxilline or lolitrem B, can be found as two disparate
      clades, not supported by prenylation type (e.g., regular or reverse). This paper
      provides insight into the P. paxilli indole-diterpene locus and reviews the
      recent advances identified in paxilline biosynthesis. 

PMID- 23949006
TI  - Non-linear relationships between aflatoxin B1 levels and the biological response
      of monkey kidney vero cells.
AB  - Aflatoxin-producing fungi contaminate food and feed during pre-harvest, storage
      and processing periods. Once consumed, aflatoxins (AFs) accumulate in tissues,
      causing illnesses in animals and humans. Most human exposure to AF seems to be a
      result of consumption of contaminated plant and animal products. The policy of
      blending and dilution of grain containing higher levels of aflatoxins with
      uncontaminated grains for use in animal feed implicitly assumes that the
      deleterious effects of low levels of the toxins are linearly correlated to
      concentration. This assumption may not be justified, since it involves
      extrapolation of these nontoxic levels in feed, which are not of further concern.
      To develop a better understanding of the significance of low dose effects, in the
      present study, we developed quantitative methods for the detection of
      biologically active aflatoxin B1 (AFB1) in Vero cells by two independent assays:
      the green fluorescent protein (GFP) assay, as a measure of protein synthesis by
      the cells, and the microculture tetrazolium (MTT) assay, as a measure of cell
      viability. The results demonstrate a non-linear dose-response relationship at the
      cellular level. AFB1 at low concentrations has an opposite biological effect to
      higher doses that inhibit protein synthesis. Additional studies showed that heat
      does not affect the stability of AFB1 in milk and that the Vero cell model can be
      used to determine the presence of bioactive AFB1 in spiked beef, lamb and turkey
      meat. The implication of the results for the cumulative effects of low amounts of
      AFB1 in numerous foods is discussed.

PMID- 23949007
TI  - The cytotoxic necrotizing factor 1 from E. coli: a janus toxin playing with
      cancer regulators.
AB  - Certain strains of Escherichia coli have been indicated as a risk factor for
      colon cancer. E. coli is a normal inhabitant of the human intestine that becomes
      pathogenic, especially in extraintestinal sites, following the acquisition of
      virulence factors, including the protein toxin CNF1. This Rho GTPases-activating
      toxin induces dysfunctions in transformed epithelial cells, such as apoptosis
      counteraction, pro-inflammatory cytokines' release, COX2 expression, NF-kB
      activation and boosted cellular motility. As cancer may arise when the same
      regulatory pathways are affected, it is conceivable to hypothesize that CNF1
      producing E. coli infections can contribute to cancer development. This review
      focuses on those aspects of CNF1 related to transformation, with the aim of
      contributing to the identification of a new possible carcinogenic agent from the
      microbial world. 

PMID- 23949008
TI  - Characterisation of an L-haloacid dehalogenase from the marine psychrophile
      Psychromonas ingrahamii with potential industrial application.
AB  - The recombinant L-haloacid dehalogenase from the marine bacterium Psychromonas
      ingrahamii has been cloned and over-expressed in Escherichia coli. It shows
      activity towards monobromoacetic (100 %), monochloroacetic acid (62 %), S
      chloropropionic acid (42 %), S-bromopropionic acid (31 %), dichloroacetic acid
      (28 %) and 2-chlorobutyric acid (10 %), respectively. The L-haloacid dehalogenase
      has highest activity towards substrates with shorter carbon chain lengths (<=
      C3), without preference towards a chlorine or bromine at the alpha-carbon
      position. Despite being isolated from a psychrophilic bacterium, the enzyme has
      mesophilic properties with an optimal temperature for activity of 45  degrees C.
      It retains above 70 % of its activity after being incubated at 65  degrees C for
      90 min before being assayed at 25  degrees C. The enzyme is relatively stable in
      organic solvents as demonstrated by activity and thermal shift analysis. The V
      max and K m were calculated to be 0.6 MUM min(-1) mg(-1) and 1.36 mM with
      monobromoacetic acid, respectively. This solvent-resistant and stable L-haloacid
      dehalogenase from P. ingrahamii has potential to be used as a biocatalyst in
      industrial processes.

PMID- 23949009
TI  - Living with an inborn error of metabolism detected by newborn screening-parents'
      perspectives on child development and impact on family life.
AB  - BACKGROUND: Newborn screening for inborn errors of metabolism is regarded as
      highly successful by health professionals. Little is known about parents'
      perspectives on child development and social impact on families. METHODS: Parents
      of 187 patients with metabolic disorders detected by newborn screening rated
      child development, perceived burdens on child and family, and future expectations
      on a questionnaire with standardized answers. Parental ratings were compared with
      standardized psychometric test results. Regression analysis was performed to
      identify factors associated with extent of perceived burden. RESULTS: In 26.2% of
      patients, parents perceived delays in global development and/or specific
      developmental domains (physical, social, intellectual, language). Parents
      expected normal future development in 95.7%, and an independent adult life for
      their child in 94.6%. Comparison with psychometric test results showed that
      parents of children with cognitive impairments tended to overrate their child's
      abilities. Mild/medium burden posed on the family (child) by the metabolic
      disorder was stated by 56.1% (48.9%) of parents, severe/very severe burden by
      19.3% (8.6%). One third of families reported financial burden due to the
      metabolic disorder. Dietary treatment and diagnoses with risk for metabolic
      decompensation despite treatment were associated with higher perceived burden for
      the family. Disorders rated as potentially very burdensome by experts were not
      rated accordingly by parents, demonstrating different perspectives of
      professionals and parents. CONCLUSION: Although newborn screening leads to
      favourable physical and cognitive outcome, living with a metabolic disorder may
      cause considerable stress on patients and families, emphasizing the need for
      comprehensive multidisciplinary care including psychological and social support.

PMID- 23949010
TI  - Cognitive dysfunction and depression in Fabry disease: a systematic review.
AB  - BACKGROUND: Fabry disease, an X-linked lysosomal storage disorder, leads to multi
      organ dysfunction, including cerebrovascular disease and psychological disorders.
      However, the prevalence and pattern of associated cognitive dysfunction is not
      well understood. OBJECTIVES: To investigate whether there is reliable evidence
      for neuropsychological impairment in patients with Fabry disease and which
      cognitive domains are affected. To estimate the prevalence of and factors
      associated with depression in patients with Fabry disease. METHOD: Qualitative
      systematic review of the literature of studies conducting neuropsychological
      assessment or measuring the prevalence of depression in adults with Fabry disease
      using the preferred reporting items for systematic reviews and meta-analysis
      (PRISMA) guidelines where appropriate. RESULTS: There is some evidence for
      neuropsychological impairment in Fabry disease in executive functioning,
      information processing speed and attention, with preservation of: general
      intellectual functioning, memory, naming, perceptual functioning and global
      cognitive functioning. Prevalence rates of depression in Fabry disease ranged
      from 15% to 62%, with the largest study to date reporting a prevalence rate of
      46%. The most common factor associated with depression was neuropathic pain, both
      directly and indirectly by affecting social and adaptive functioning. CONCLUSION:
      Our review suggests that Fabry disease may be associated with a characteristic
      pattern of cognitive deficits and a high prevalence of psychological disorders
      such as depression but highlights the limited available data. Exploring the
      nature of cognitive impairment in Fabry disease using standardised
      neuropsychological assessment, brain imaging and measures of depression is an
      important task for future research.

PMID- 23949011
TI  - MPT0B169, a new tubulin inhibitor, inhibits cell growth and induces G2/M arrest
      in nonresistant and paclitaxel-resistant cancer cells.
AB  - The polymerization of tubulin molecules forms microtubules which are considered
      an attractive target for cancer treatment. Herein, we synthesized a new tubulin
      inhibitor, MPT0B169 (2-dimethylamino-N-[1-(4-methoxy-benzenesulfonyl)-2,3-dihydro
      1H-indol-7-yl]-acetamide) and demonstrated its action in leukemia cell lines HL60
      and NB4 and lymphoma cell line U937. We found that MPT0B169 prevented tubulin
      assembly by binding the colchicine-binding site of tubulin in vitro. MPT0B169
      also induced tubulin depolymerization in vivo. MPT0B169 inhibited the growth of
      HL60, NB4, and U937 cells in dose- and time-dependent manners. It also inhibited
      the growth of paclitaxel-resistant cancer cells. In addition, MPT0B169 caused
      G2/M cell cycle arrest in nonresistant and paclitaxel-resistant cancer cells,
      with a concomitant increase in cyclin B1 levels and cyclin-dependent kinase 1
      (CDK1) phosphorylation. These results suggest that MPT0B169, a tubulin inhibitor,
      inhibits cell growth and induces G2/M cell cycle arrest of cancer cells through
      the disruption of tubulin polymerization. 

PMID- 23949012
TI  - Healthy aging: what can we learn from Caenorhabditis elegans?
AB  - The microscopic worm Caenorhabditis elegans (C. elegans) is one of the most
      prominent animal models for aging studies. This is underscored by the fact that
      most of the genes and interventions that modulate the aging process, such as the
      insulin/IGF pathway, caloric restriction and mitochondrial signalling, were first
      identified in this organism. Remarkably, many features of the mammalian aging
      process are recapitulated in C. elegans: over time, damage to macromolecule
      accumulates, structural cellular components progressively deteriorate,
      physiological functions decline, resistance to stress and infections decreases,
      while morbidity and mortality rates increase. In humans, age represents risk
      factor number one for most diseases ultimately leading to death in industrialized
      countries, namely cardiovascular diseases, cancer and neurodegenerative
      disorders. Genes regulating aging in C. elegans are evolutionarily conserved and
      their deregulation is often involved in the development of age-associated
      diseases in humans. It is therefore likely that any intervention that extends C.
      elegans lifespan will indicate strategies to positively impact on healthy human
      longevity. 

PMID- 23949013
TI  - Depression among long-term survivors of head and neck cancer treated with
      radiation therapy.
AB  - IMPORTANCE: The diagnosis and subsequent treatment of head and neck cancer can
      have a potentially devastating impact on psychosocial functioning. Although the
      long-term physical adverse effects of radiation therapy (RT) for head and neck
      cancer have been well described, relatively few studies have evaluated
      psychosocial functioning after treatment. OBJECTIVE: To determine the prevalence
      of self-reported depression among survivors of head and neck cancer returning for
      follow-up after being treated with RT. DESIGN, SETTING, AND PARTICIPANTS: Cross
      sectional analysis among 211 comprehensive cancer center patients with squamous
      cell carcinoma of the head and neck, who had been previously treated with RT and
      were disease-free with at least 1 year of follow-up. Patients with a history of
      mood disorder, use of mental health services in the past, or previous or current
      use of antidepressants or anxiolytics, excluding sleep medications, were
      specifically excluded. INTERVENTIONS: The University of Washington Quality of
      Life instrument (UW-QOL), a brief, previously validated, self-administered
      questionnaire, was used to analyze rates of depression. MAIN OUTCOMES AND
      MEASURES: The UW-QOL assigned scores of 0, 25, 50, 75, and 100 subjective
      responses of mood being "extremely depressed," "somewhat depressed," "neither in
      a good mood or depressed," "generally good," and "excellent," respectively.
      RESULTS: The mean mood score did not differ at 1, 3, and 5 years after treatment,
      with scores of 52.0, 55.7, and 62.1, respectively. The proportion of patients who
      reported their mood as "somewhat depressed" or "extremely depressed" was 17%,
      15%, and 13% at 1, 3, and 5 years, respectively. Variables that were
      significantly associated with post-RT depression included the presence of
      tracheostomy tube or laryngeal stoma (P = .01), gastrostomy tube dependence (P =
      .01), and continued smoking at the time of follow-up (P < .001). Among the
      patients reporting their mood as either "somewhat depressed" or "extremely
      depressed" at 1, 3, and 5 years, the proportion using antidepressants at the time
      was 6%, 11%, and 0%, respectively. The corresponding proportion of patients
      actively undergoing or seeking psychotherapy and/or counseling was 3%, 6%, and
      0%, respectively. CONCLUSIONS AND RELEVANCE: Despite a relatively high rate of
      depression among patients with head and neck cancer in the post-RT setting,
      mental health services are severely underutilized.

PMID- 23949014
TI  - Role of the P2X7 receptor in the osteogenic differentiation of mesenchymal cells
      and in osteoclast fusion : presented by: Maria P. Abbracchio.

PMID- 23949015
TI  - LED and laser photobiomodulation in the prevention and treatment of oral
      mucositis: experimental study in hamsters.
AB  - PURPOSE: This paper aims to evaluate the effects of laser (660 nm) and light
      emitting diode (LED) (670 nm) irradiation in the cheek pouch mucosa of hamsters
      with oral mucositis (OM) induced by chemotherapy (Che) with 5-fluorouracil (5
      FU). MATERIALS AND METHODS: In the preventive groups, the photobiomodulation was
      started 1 day before the drug administration and was performed every 48 h (Ia,
      IIa, Ib, and IIb). In the therapeutic groups (IIIa, IIIb, IVa, and IVb), the
      irradiations were started on the third day after the Che d(0) and was performed
      every 48 h. In both groups, animals were sacrificed 7 or 14 days after Che. In
      the positive control groups, the hamsters were subjected to Che but did not
      receive irradiation, and they were sacrificed in 7 days (Va) or 14 days (Vb). In
      the negative control groups, no procedures were done and the animals were
      sacrificed 7 days (Vc) or 14 days (Vd) after the experiment started. RESULTS: The
      results indicated loss of body mass, xerostomia, and alopecia in the animals
      subjected to Che and the healing of OM to different degrees after the
      photobiomodulation treatment. Histologically, the positive control and
      experimental groups showed inflammation, predominately with lymphocytes and
      plasma cells, which tended to diminish with time. Epithelial atrophy, hyperemia,
      fibroblast proliferation, and vascular congestion were also observed at those
      intervals. CONCLUSIONS: The best results were obtained from the preventive laser
      and LED photobiomodulation groups; both treatments were effective in diminishing
      the OM lesions. CLINICAL RELEVANCE: A noninvasive and effective method with
      sparse side effects of OM would be desirable for use in cancer centers around the
      world.

PMID- 23949016
TI  - Five-year clinical performance of a HEMA-free one-step self-etch adhesive in
      noncarious cervical lesions.
AB  - OBJECTIVES: The objective of this randomized controlled trial was to evaluate the
      clinical performance of a 2-hydroxyethyl methacrylate (HEMA)-free one-step
      adhesive. MATERIALS AND METHODS: Two hundred sixty-seven cervical lesions in 52
      patients were restored with the composite Gradia Direct (GC), bonded with either
      the one-step self-etch adhesive G-Bond (GC) or the three-step etch-and-rinse
      adhesive Optibond FL (Kerr) in a random order. The restorations were evaluated
      for retention, marginal integrity, marginal discoloration, and caries occurrence
      after 5 years. Specific statistics were used to account for the clustered data
      (multiple restorations per patient). RESULTS: The clinical success rate for G
      Bond (87.4 %) was not significantly different from that of Optibond FL (90.9 %).
      Both adhesives showed progressive marginal deterioration, but G-Bond exhibited
      more small enamel defects and marginal discoloration, and unlike previous
      recalls, several restorations failed because of deep microleakage. Large
      sclerotic lesions were a significant risk factor for retention loss with G-Bond.
      Irrespective of the adhesive, almost all restorations with retention loss were
      located in the lower jaw. CONCLUSION: After 5 years of clinical service,
      restorations bonded with the HEMA-free one-step adhesive did not need repair or
      replacement more often than those with the three-step etch-and-rinse adhesive,
      and both adhesives had a high retention rate (>90 %). There were indications that
      G-Bond did not (self-)etch enough in some clinical situations, as G-Bond
      exhibited more incisal defects and marginal discolorations, and sclerotic lesions
      were at higher risk of retention loss. CLINICAL RELEVANCE: The clinical
      performance of the HEMA-free one-step adhesive was clinically acceptable after 5
      years.

PMID- 23949017
TI  - DeltaNp63 expression in four carcinoma cell lines and the effect on
      radioresistance--a siRNA knockdown model.
AB  - OBJECTIVES: This study investigated the expression of DeltaNp63alpha in carcinoma
      cell lines of the upper aerodigestive tract and their potential influence on
      radioresistance using a small interfering RNA (siRNA) knockdown approach.
      MATERIALS AND METHODS: Four carcinoma cell lines were investigated for the
      expression of the DeltaNp63 isoform by quantitative reverse transcriptase
      polymerase chain reaction (qRT-PCR) (0, 24, 48 h) with and without single dose
      irradiation of 6 Gy. Furthermore, all cell lines were transfected with siRNA
      against the DeltaNp63alpha isoform over 24 h. Knockdown effectiveness was
      controlled by qRT-PCR and Western blot. Apoptotic events were evaluated by
      terminal transferase dUTP nick end labeling (TUNEL) assay and cross-checked by a
      test for cell viability (WST-1, Roche) over 48 h. RESULTS: All cell lines
      presented varying expression of the DeltaNp63alpha isoform with and without
      irradiation. A sufficient knockdown rate was established by siRNA transfection.
      Knockdown of the DeltaNp63 isoform showed an effect on radiation sensitivity
      proven by an increase of apoptotic events detectable by immunofluorescence (TUNEL
      assay) and likewise a significant reduction of formazan production (WST-1 test)
      in three cell lines. CONCLUSIONS: We found overexpression of DeltaNp63alpha with
      and without irradiation in three cell lines, and the knockdown of DeltaNp63alpha
      led to increased apoptotic events and fewer viable cells. Thus, the
      overexpression of DeltaNp63alpha might protect carcinoma cells against
      irradiation effects. CLINICAL RELEVANCE: The present work supports the hypothesis
      that protein 63 might serve as a negative predictor for irradiation response and
      survival in a clinical setting and may be a target for future therapeutic
      strategies.

PMID- 23949018
TI  - Three-year randomized clinical evaluation of a low-shrinkage silorane-based resin
      composite in non-carious cervical lesions.
AB  - OBJECTIVE: The clinical suitability of low-shrinkage resin composites for class V
      cavities has not been investigated in vivo. The purpose of this double-blind
      randomized clinical trial was to compare the clinical performances of low
      shrinkage resin composite Filtek silorane and nanoceramic resin composite Ceram X
      mono in non-carious cervical lesions (NCCLs) over 36 months. MATERIALS AND
      METHODS: Two calibrated operators restored 144 NCCLs in 24 patients by using
      Filtek silorane with silorane system adhesive (FS/SSA) and Ceram X mono with
      Clearfil SE (CXM/CSE) or XP bond (CXM/XPB). Then, two blinded, calibrated
      evaluators assessed the restorations at the baseline and 6, 12, 24, and 36 months
      thereafter by using the modified US Public Health Service criteria. Data were
      analyzed with the Freidman and Wilcoxon signed-rank tests at a significance level
      of 5 % (P < 0.05). RESULTS: No restoration was associated with postoperative
      sensitivity or secondary caries. Further, no group showed significant changes
      until 12 months. The retention rates of the FS/SSA (97.5 %), CXM/CSE (97.5 %),
      and CXM/XPB (92.31 %) restorations did not differ significantly (P > 0.05). Six
      (4 CXM/XPB, 1 FS/SSA, and 1 CXM/CSE) of the 121 restorations evaluated at 36
      months were completely lost. However, no significant intergroup differences were
      observed in the other evaluation criteria. CONCLUSION: The 3-year clinical
      performances of the restorative materials in NCCLs were not significantly
      different. CLINICAL RELEVANCE: Filtek silorane is suitable for restoring NCCLs.

PMID- 23949019
TI  - In vitro culture system for keratinocytes obtained from oral lichen planus
      lesions.
AB  - OBJECTIVES: The aim of this study was to establish a stable in vitro culture
      system for keratinocytes obtained from oral lichen planus (OLP) lesions and
      evaluate cultured keratinocyte characteristics including cell morphology,
      ultrastructure, and expression of biomarkers. MATERIALS AND METHODS: OLP mucosa
      (histopathologically confirmed) was collected and cells isolated using the cold
      enzyme digestion method. Primary culture and serial passage were performed on
      serum-free keratinocyte medium. Morphological changes of cells were evaluated via
      inverted phase contrast microscopy, and cellular ultrastructure was observed by
      electron microscopy. Indirect immunofluorescence was used to detect expression of
      keratin and nuclear factor-kappaB (NF-kappaB). RESULTS: OLP type I keratinocytes
      was successfully cultured in vitro in serum-free medium. Cellular morphology was
      typically polygonal during the growth phase. Cells could be passaged continuously
      for five to six generations without losing viability. Transmission electron
      microscopy showed large nuclei and multiple vacuoles in the cultured cells
      consistent with histopathological features of OLP keratinocytes. Indirect
      immunofluorescence staining was positive for keratin and NF-kappaB. CONCLUSIONS:
      This study established that human OLP kera-tinocytes can be successfully cultured
      cells with histopathologic features and biomarker expression consistent with OLP
      type I keratinocytes. CLINICAL RELEVANCE: This culture system lays a foundation
      for the establishment of human OLP cell model in vitro.

PMID- 23949020
TI  - World Health Organization approaches for surveys of health behaviour among
      schoolchildren and for health-promoting schools.
AB  - Adolescents make up about one-sixth of the world's population. Most of the
      healthy and detrimental habits are adopted during childhood and adolescence. In
      the mid 1980s, a cross-national Health Behaviour in School-Aged Children (HBSC)
      survey was created to increase information about the well-being, health
      behaviours and social context of young people by using standard school-based
      questionnaires adopted by the World Health Organization (WHO) European office.
      The European Network of Health-Promoting Schools (HPS) was commenced in 1992,
      followed by the establishment of the WHO Global School Health Initiative in 1995.
      The initiative aims to improve the health of students, school personnel, families
      and other members of the community through schools by mobilizing and
      strengthening health promotion and educational activities at local, national,
      regional and global levels. The HBSC and HPS programmes have been accepted as
      activity areas for the WHO Collaborating Centre for Primary Oral Health Care in
      Kuwait. This article describes the HBSC and the HPS programmes and discusses the
      importance of establishing these programmes in Kuwait.

PMID- 23949021
TI  - Transparent flexible organic solar cells with 6.87% efficiency manufactured by an
      all-solution process.
AB  - We demonstrate that polyaniline (PANI) behaves as an anode buffer layer, which
      makes it an excellent hole transport layer. PANI was coated between the
      photoactive layer and the top anode in transparent flexible organic solar cells
      (OSCs). The performances of the devices with different PANI thicknesses were
      investigated. The results demonstrate that the power conversion efficiency (PCE)
      increased nearly four-fold with an 18 nm thick PANI layer compared to the
      reference cell without PANI. The optimum device performance with an 18 nm PANI
      layer exhibits a Jsc of 11.60 mA cm(-2), a V(oc) of 0.89 V, a FF of 66.87%, and
      thus a PCE of 6.87% under AM1.5G illumination of 100 mW cm(-2). The conversion
      efficiency of transparent flexible OSCs changes after 1500 bending cycles.

PMID- 23949022
TI  - Current choroidal neovascularization treatment.
AB  - PURPOSE: This paper aims to describe the current situation of choroidal
      neovascularization (CNV) treatment. PROCEDURES: MEDLINE (2001-2013) was searched
      for original research studies (phase I, II, III), abstracts and review articles
      concerning CNV therapy, and other related articles. Selected information from
      related websites was also included. RESULTS: The management of CNV was developed
      through laser photocoagulation and photodynamic therapy, and has now evolved into
      anti-vascular endothelial growth factor (VEGF) use. Patients have achieved better
      visual acuity and toleration with the development of this therapy strategy.
      Combination therapy appears to offer a reduced retreatment frequency and long
      term maintenance of the benefit with appropriate combination. Other treatment
      explorations with anti-inflammation and anti-VEGF are also ongoing. CONCLUSIONS:
      Anti-VEGF monotherapy has become the first treatment for CNV patients. The
      investigation of other therapy strategies may prolong the interval of treatment
      and provide alternatives to CNV treatment.

PMID- 23949023
TI  - Integrating robot-assisted interventions into standard of care.

PMID- 23949024
TI  - Effects of proximal and distal robot-assisted upper limb rehabilitation on
      chronic stroke recovery.
AB  - OBJECTIVE: To evaluate the effects of add-on distal upper limb robot-assisted
      treatment on the outcome of proximal regions. DESIGN: 64 chronic stroke patients
      divided into two groups participated in the study. Group A was assigned to the
      proximal robot-assisted rehabilitation, Group B to the proximal and distal.
      Shoulder/elbow subsection of Fugl-Meyer Assessment scale was collected for Group
      A, whereas for Group B wrist subsection was also collected. Motricity Index was
      used and a set of kinematic parameters was computed for both groups. RESULTS: A
      decrease in impairment after the treatment in both groups of patients (Group A:
      Shoulder/elbow FM p < 0.001 and MI p < 0.001; Group B: Shoulder/elbow FM p <
      0.001 and MI p < 0.001) was found. In the Group B wrist subsection of FM showed
      an improvement as well (p < 0.001). No difference between groups was found in
      changes of clinical scales. Movement velocity and accuracy increased after the
      robot-assisted treatment in both groups; group B showed a greater improvement in
      velocity. CONCLUSIONS: Robotic treatment is effective to reduce motor impairment
      in chronic stroke patients even if distal training added to proximal segments in
      the Group B does not provide any incremental benefit to the proximal segments. It
      remains unclear if the effectiveness of robot-assisted treatment is directly
      related to the upper limb segment specifically treated and which order may lead
      to better outcome. Our study suggests that kinematic parameters should be
      computed in order to better clarify the role of distal training (wrist) on
      proximal segments (shoulder/elbow) as well.

PMID- 23949025
TI  - The effect of random or sequential presentation of targets during robot-assisted
      therapy on children.
AB  - BACKGROUND: Robot assisted upper extremity therapy has been shown to be effective
      in adult stroke patients and in children with cerebral palsy (CP) and other
      acquired brain injuries (ABI). The patient's active involvement is a factor in
      its efficacy. However, this demands focused attention during training sessions,
      which can be a challenge for children. OBJECTIVE: To compare results of training
      requiring two different levels of focused attention. Differences in short term
      performance and retention of gains as a function of training protocol as measured
      by the Fugl-Meyer (FM) were predicted. METHODS: Thirty-one children with CP or
      ABI were randomly divided into two groups. All received 16 one hour sessions of
      robot-assisted therapy (twice a week for 8 weeks) where they moved a robot handle
      to direct a cursor on the screen toward designated targets. One group had targets
      presented sequentially in clockwise fashion, the other presented in random order.
      Thus, one group could anticipate the position of each target, the other could
      not. RESULTS: Both groups showed significant functional improvement after
      therapy, but no significant difference between groups was observed. CONCLUSIONS:
      Assist-as-needed robotic training is effective in children with CP or ABI with
      small non-significant differences attributed to attentional demand.

PMID- 23949026
TI  - Targeted engagement of a dorsal premotor circuit in the treatment of post-stroke
      paresis.
AB  - BACKGROUND: Good motor outcome after stroke has been found to correlate with
      increased activity in a dorsal premotor (PMd) brain circuit, suggesting that
      therapeutic strategies targeting this circuit might have a favorable, causal
      influence on motor status. OBJECTIVE: This study addressed the hypothesis that a
      Premotor Therapy that exercises normal PMd functions would provide greater
      behavioral gains than would standard Motor Therapy; and that Premotor Therapy
      benefits would be greatest in patients with greater preservation of PMd circuit
      elements. METHODS: Patients with chronic hemiparetic stroke (n = 15) were
      randomized to 2-weeks of Premotor Therapy or Motor Therapy, implemented through a
      robotic device. RESULTS: Overall, gains were modest but significant (change in FM
      score, 2.1 +/- 2.8 points, p < 0.02) and did not differ by treatment assignment.
      However, a difference between Therapies was apparent when injury to the PMd
      circuit was considered, as the interaction between treatment assignment and
      degree of corticospinal tract injury was significantly related to the change in
      FM score (p = 0.018): the more the corticospinal tract was spared, the greater
      the gains provided by Premotor Therapy. Similar results were obtained when
      looking at the interaction between treatment assignment and PMd function (p =
      0.03). CONCLUSIONS: Targeted engagement of a brain circuit is a feasible strategy
      for stroke rehabilitation. This approach has maximum impact when there is less
      stroke injury to key elements of the targeted circuit.

PMID- 23949027
TI  - The associations between motor ability, walking activity and heart rate and heart
      rate variability parameters among children with cerebral palsy and typically
      developed controls.
AB  - AIMS: To measure heart rate (HR) and heart rate variability (HRV) at rest, during
      and after walking among children with cerebral palsy (CP) as compared to age
      matched typically developed (TD) controls. The second aim was to describe the
      association between HRV and motor performance in children with CP. METHODS:
      Twenty six children with CP (age 8-14 years) and sixteen TD children matched for
      age assessed during rest, walking and after walking. HR and HRV parameters
      include: time domain parameters: standard deviation of the R-R interval (SDNN),
      square root of the mean squared differences of successive R-R differences
      (RMSSD). RESULTS: Children with CP demonstrated higher mean HR values at rest;
      98.4 +/- 13.9 bpm vs 83.0 +/- 11.5 bpm in controls, (p < 0.05) and significantly
      lower time domain measures of HRV; RMSSD was 52.0 +/- 19.1 ms and 87.0 +/- 39.8
      ms respectively (p < 0.05). Significant interaction effects were noted for HR and
      time domain HRV parameters. HR increased and SDNN and RMSSD decreased when
      children change their activity level from rest to walking and HR decreased and
      SDNN and RMSSD increased again after walking for TD children but not for children
      with CP (p < 0.05). No association was noted between HRV and motor performance in
      children with CP. INTERPRETATION: The findings of this study suggest that among
      children with CP, the cardiac autonomic mechanism is less efficient at rest and
      less adaptive to exercise and activity as compared to TD children.

PMID- 23949028
TI  - Transcranial direct current stimulation (tDCS) and robotic practice in chronic
      stroke: the dimension of timing.
AB  - BACKGROUND: Combining tDCS with robotic therapy is a new and promising form of
      neurorehabilitation after stroke, however the effectiveness of this approach is
      likely to be influenced by the relative timing of the brain stimulation and the
      therapy. OBJECTIVE: To measure the kinematic and neurophysiological effects of
      delivering tDCS before, during and after a single session of robotic motor
      practice (wrist extension). METHODS: We used a within-subjects repeated
      measurement design in 12 chronic (>6 months) stroke survivors. Twenty minutes of
      anodal tDCS was delivered to the affected hemisphere before, during, or after a
      20-minute session of robotic practice. Sham tDCS was also applied during motor
      practice. Robotic motor performance and corticomotor excitability, assessed
      through transcranial magnetic stimulation (TMS), were evaluated pre- and post
      intervention. RESULTS: Movement speed was increased after motor training (sham
      tDCS) by ~20%. Movement smoothness was improved when tDCS was delivered before
      motor practice (~15%). TDCS delivered during practice did not offer any benefit,
      whereas it reduced speed when delivered after practice (~10%). MEPs were present
      in ~50% of patients at baseline; in these subjects motor practice increased
      corticomotor excitability to the trained muscle. CONCLUSIONS: In a cohort of
      stroke survivors, motor performance kinematics improved when tDCS was delivered
      prior to robotic training, but not when delivered during or after training. The
      temporal relationship between non-invasive brain stimulation and
      neurorehabilitation is important in determining the efficacy and outcome of this
      combined therapy.

PMID- 23949029
TI  - Effects of prolonged robot-assisted training on upper limb motor recovery in
      subacute stroke.
AB  - BACKGROUND: High intensity and early initiation of rehabilitation have been
      extensively demonstrated to enhance neural plasticity and motor recovery after
      stroke. However, the optimal duration of rehabilitation programs in order to have
      the highest impact on motor outcomes has not been established. OBJECTIVES: To
      evaluate motor outcomes in subacute stroke survivors with moderate to severe
      upper limb paresis over an extended period of rehabilitation consisting of usual
      care augmented with a large number of upper limb robot-assisted sessions (54 +/-
      13 sessions). METHODS: Retrospective study in 10 inpatients. RESULTS: The results
      showed a gradual decrease in motor and functional impairments throughout the
      training period with a clinically meaningful increase in the Fugl-Meyer
      Assessment scores and in the Motor Status Scores (1st vs 37th day of the
      training, FMA,+ 48%, p = 0.018, MSS,+ 64%, p = 0.012; 37th vs. 79th day, FMA,+
      23%, p = 0.012, MSS,+ 30%, p = 0.017). In addition, there were improvements in
      hand kinematics recorded by the robot during a pointing task, with quantitative
      improvement (1st vs 40th day, movement efficacy,+ 97%, p = 0.0499; hand
      velocity,+ 335%, p = 0.013) prior to qualitative improvement (1st vs 80th day,
      number of hand trajectory reversals, -50%, p = 0.028; root mean square error of
      the trajectory/linear displacement, -52%, p = 0.059). CONCLUSIONS: Although this
      study was a retrospective analysis of a small sample of patients, the results
      suggested that a prolonged period of intensive upper limb rehabilitation,
      including robot-assisted training incorporated into a multidisciplinary program
      throughout the subacute phase after stroke resulted in significant improvements
      in patients with moderate to severe motor impairments.

PMID- 23949030
TI  - Excitability of spinal neural function during several motor imagery tasks
      involving isometric opponens pollicis activity.
AB  - BACKGROUND: It is unclear whether mental simulation without actual muscle
      contraction associated with actual motion can increase the excitability of the
      spinal neural function. OBJECTIVE: To determine the best method for mental
      simulation without actual muscle contraction, we analyzed the F-wave of thenar
      muscles after stimulating the median nerve by motor imagery whilst holding the
      sensor of a pinch meter between the thumb and index finger and without holding
      the sensor. METHODS: Healthy volunteers (n = 11; mean age, 34 years) participated
      in this study after providing informed consent. We examined the F-wave of the
      left thenar muscles after stimulating the left median nerve at the wrist at rest
      and under holding and motor imagery conditions. For the motor imagery condition,
      the subjects were asked to establish 50% maximal voluntary contraction (MVC) of
      isometric contraction while holding the sensor between the thumb and index finger
      (motor imagery with the sensor condition) and without holding the sensor on
      another day (motor imagery without the sensor condition). RESULTS: The
      persistence and amplitude ratio of F/M during motor imagery with or without the
      sensor was better than that during relaxation. In particular, this ratio was
      significantly higher under the with sensor condition than under the without
      sensor condition. CONCLUSION: Movement preparation for a motor imagery task
      involving 50% MVC isometric contraction of the opponens pollicis is important.

PMID- 23949031
TI  - Gorham's disease of the spine.
AB  - BACKGROUND: Gorham's disease of the spine is very rare and usually associated
      with poor prognosis. Till date very few cases have been reported in the
      literature. It is characterized by osseous invasion by angiomatous vascular mass
      without skip areas, eventually causing lysis of affected bone. Morbidity and
      mortality are high in those with spinal and/or visceral involvement. Neurological
      complications increase the mortality to 33% whereas with chylothorax, mortality
      increases to more than 50%. OBJECTIVES: To describe the clinical course and the
      challenges in planning and implementing effective rehabilitation services for
      management of patients with Gorham's disease of the spine. METHODS: We report two
      patients with Gorham's disease who had neurological deficits secondary to spinal
      cord involvement, and their rehabilitation perspectives. RESULTS: Both patients
      achieved satisfactory ambulation and functional outcomes. CONCLUSION: Multiple
      revision surgeries may be required to ensure spinal stability. When working with
      these patients, one must remain vigilant about spinal stability as well as about
      possible serious pulmonary complications, and be prepared to make appropriate
      management decisions when necessary.

PMID- 23949032
TI  - Effect of EMG biofeedback training of gluteus maximus muscle on gait parameters
      in incomplete spinal cord injury.
AB  - STUDY DESIGN: A Pretest -Posttest Experimental Design. OBJECTIVES: Patients with
      incomplete spinal cord injury (ISCI) retain or regain the ability to walk, but
      due to limitations in gait parameters, walking may not be the practical method of
      mobility in the community. Specific muscle training plays an important role in
      gait training. The purpose of this study was to determine the effect of EMG
      Biofeedback training of gluteus maximus muscle on gait parameters in ISCI
      patients. SETTING: Indian Spinal Injury Center, New Delhi, India. SUBJECTS: 30
      incomplete spinal cord injured (ISCI) patients were included and randomly
      assigned to two groups. Group 1 received EMG Biofeedback (EMG BF), Traditional
      Rehabilitation and Gait Training. Group 2 received Traditional Rehabilitation and
      Gait Training. METHODS: Gait parameters were measured prior to the intervention
      for all 30 ISCI patients. EMG Biofeedback was given specifically over gluteus
      maximus muscle along with traditional rehabilitation and gait training to Group 1
      for 5 days/week for 4 weeks. Group 2 received traditional rehabilitation and gait
      training for 5 days/week for 4 weeks. The results were interpreted on the basis
      of: EMG amplitude, step length, walking velocity and cadence. RESULTS: Results
      showed significant difference between two groups for EMG amplitude (t = 6.06, p =
      0.001), walking velocity (t = 2.12, p = 0.043), cadence (t = 1.96, p = 0.05).
      Step length did not show any significant difference (t = 0.66, p = 0.512).
      CONCLUSION: The study concluded that EMG BF when given specifically over gluteus
      maximus resulted in improvement of EMG amplitude and various gait parameters
      (walking velocity, cadence).

PMID- 23949033
TI  - Strength and endurance adaptations to functional electrical stimulation leg cycle
      ergometry in spinal cord injury.
AB  - OBJECTIVES: To describe adaptations in power output, quadriceps muscle strength,
      and fatigability that occur during a 13-week regimen of Functional Electrical
      Stimulation Leg Cycle Ergometry (FES-LCE) in Spinal Cord Injury (SCI). To
      identify differences in outcomes between individuals with complete and incomplete
      motor impairment. DESIGN: Observational and longitudinal. SETTING: Rehabilitation
      and biomechanics research laboratory. PARTICIPANTS: Eleven (N = 11) individuals
      with SCI and no previous FES-LCE experience. INTERVENTION: 40 sessions of FES-LCE
      at a rate of three sessions per week. Continuous exercise was performed at a
      pedal cadence of 45 RPM against a constant resistance for up to 60 minutes.
      OUTCOME MEASURES: Mean power output was recorded for each session. Before and
      after the training regimen, each subject performed a fatigue test in which
      electrically stimulated knee extension torque and Fatigue Index were measured.
      RESULTS: Participants demonstrated significant increases in mean power output
      (9.0 to 20.3 W; p < 0.001), peak isometric knee extension torque (3.8 to 16.9 Nm;
      p = 0.006) and sustainable isometric knee extension torque (4.9 to 14.4 Nm; p =
      0.001) after FES-LCE training (95% confidence intervals). Participants with
      incomplete motor impairment demonstrated a decrease in Fatigue Index (p = 0.021),
      and improved mean power output more than those with complete motor impairment (p
      = 0.037). CONCLUSIONS: Significant improvements in muscle conditioning and
      exercise performance are possible following the 13-week regimen of FES-LCE
      described in this article. Individuals with incomplete motor impairment
      experience greater improvements in mean power output than individuals with
      complete motor impairment.

PMID- 23949034
TI  - Improved motor performance in chronic spinal cord injury following upper-limb
      robotic training.
AB  - BACKGROUND: Recovering upper-limb motor function has important implications for
      improving independence of patients with tetraplegia after traumatic spinal cord
      injury (SCI). OBJECTIVE: To evaluate the feasibility, safety and effectiveness of
      robotic-assisted training of upper limb in a chronic SCI population. METHODS: A
      total of 10 chronic tetraplegic SCI patients (C4 to C6 level of injury, American
      Spinal Injury Association Impairment Scale, A to D) participated in a 6-week
      wrist-robot training protocol (1 hour/day 3 times/week). The following outcome
      measures were recorded at baseline and after the robotic training: a) motor
      performance, assessed by robot-measured kinematics, b) corticospinal excitability
      measured by transcranial magnetic stimulation (TMS), and c) changes in clinical
      scales: motor strength (Upper extremity motor score), pain level (Visual Analog
      Scale) and spasticity (Modified Ashworth scale). RESULTS: No adverse effects were
      observed during or after the robotic training. Statistically significant
      improvements were found in motor performance kinematics: aim (pre 1.17 +/- 0.11
      raduans, post 1.03 +/- 0.08 raduans, p = 0.03) and smoothness of movement (pre
      0.26 +/- 0.03, post 0.31 +/- 0.02, p = 0.03). These changes were not accompanied
      by changes in upper-extremity muscle strength or corticospinal excitability. No
      changes in pain or spasticity were found. CONCLUSIONS: Robotic-assisted training
      of the upper limb over six weeks is a feasible and safe intervention that can
      enhance movement kinematics without negatively affecting pain or spasticity in
      chronic SCI. In addition, robot-assisted devices are an excellent tool to
      quantify motor performance (kinematics) and can be used to sensitively measure
      changes after a given rehabilitative intervention.

PMID- 23949036
TI  - Wearable Power-Assist Locomotor (WPAL) for supporting upright walking in persons
      with paraplegia.
AB  - BACKGROUND: Due to physical and psychosocial issues associated with long-term
      sitting in a wheelchair, devising new ways to facilitate upright mobility is a
      key issue in rehabilitation medicine. Wearable Power-Assist Locomotor (WPAL) is a
      motorized orthosis and is developed for providing independent and comfortable
      walking for paraplegic patients. METHODS: The WPAL consists of a wearable robotic
      orthosis and custom walker. To facilitate alternate usage with a wheelchair, the
      wearable robotic orthosis is based on a medial system with motors located at the
      bilateral hip, knee and ankle joints to reduce the increase in heart rate during
      gait. The gait parameters include stride length, toe clearance height, swing
      time, double support time, etc. (gait speed: up to 1.3 km/h). Independent gait
      with the walker can be learned through a five-stage gait exercise sequence. The
      first two stages are stepping and gait exercises with parallel bars. The third
      stage is gait exercise on treadmill. The subsequent two stages are gait exercise
      with walker. RESULTS: Seven motor-complete paraplegic patients (spinal cord
      functional levels: T6-T12) participated. Through a series of exercises, all users
      achieved independent gait on a level floor (Functional Ambulation Categories: 4).
      The mean duration and distance of consecutively walking were 14.1 +/- 11.4
      minutes and 165.6 +/- 202.6 m, respectively. The most competent user was able to
      walk continuously for as long as 40 minutes and 640 m whereas only for 6 minutes
      and 107 m with a conventional orthosis. CONCLUSIONS: These results suggest that
      WPAL might be useful device for supporting upright walking in persons with
      paraplegia.

PMID- 23949035
TI  - Brain stimulation paired with novel locomotor training with robotic gait orthosis
      in chronic stroke: a feasibility study.
AB  - OBJECTIVES: 1) To investigate the feasibility of combining transcranial direct
      current stimulation (tDCS) to the lower extremity (LE) motor cortex with novel
      locomotor training to facilitate gait in subjects with chronic stroke and low
      ambulatory status, and 2) to obtain insight from study subjects and their
      caregivers to inform future trial design. METHODS: Double-blind, randomized
      controlled study with additional qualitative exploratory descriptive design. One
      month follow-up.10 subjects with stroke were recruited and randomized to active
      tDCS or sham tDCS for 12 sessions. Both groups participated in identical
      locomotor training with a robotic gait orthosis (RGO) following each tDCS
      session. RGO training protocol was designed to harness cortical neuroplasticity.
      Data analysis included assessment of functional and participation outcome
      measures and qualitative thematic analysis. RESULTS: Eight subjects completed the
      study. Both groups demonstrated trends toward improvement, but the active tDCS
      group showed greater improvement than the sham group. Qualitative analyses
      indicated beneficial effects of this combined intervention. CONCLUSIONS: It is
      feasible to combine tDCS targeting the LE motor cortex with our novel locomotor
      training. It appears that tDCS has the potential to enhance the effectiveness of
      gait training in chronic stroke. Insights from participants provide additional
      guidance in designing future trials.

PMID- 23949037
TI  - Evidence of end-effector based gait machines in gait rehabilitation after CNS
      lesion.
AB  - BACKGROUND: A task-specific repetitive approach in gait rehabilitation after CNS
      lesion is well accepted nowadays. To ease the therapists' and patients' physical
      effort, the past two decades have seen the introduction of gait machines to
      intensify the amount of gait practice. Two principles have emerged, an
      exoskeleton- and an endeffector-based approach. Both systems share the harness
      and the body weight support. With the end-effector-based devices, the patients'
      feet are positioned on two foot plates, whose movements simulate stance and swing
      phase. OBJECTIVE: This article provides an overview on the end-effector based
      machine's effectiveness regarding the restoration of gait. METHODS: For the
      electromechanical gait trainer GT I, a meta analysis identified nine controlled
      trials (RCT) in stroke subjects (n = 568) and were analyzed to detect differences
      between end-effector-based locomotion + physiotherapy and physiotherapy alone.
      RESULTS: Patients practising with the machine effected in a superior gait ability
      (210 out of 319 patients, 65.8% vs. 96 out of 249 patients, 38.6%, respectively,
      Z = 2.29, p = 0.020), due to a larger training intensity. Only single RCTs have
      been reported for other devices and etiologies. CONCLUSION: The introduction of
      end-effector based gait machines has opened a new succesful chapter in gait
      rehabilitation after CNS lesion.

PMID- 23949038
TI  - Efficacy of physical therapy in multiple sclerosis as measured with the modified
      fatigue impact scale and ambulation index: a retrospective study.
AB  - OBJECTIVE: Evaluate the efficacy of outcome measures routinely used in a physical
      therapy service for Multiple Sclerosis (MS). DESIGN: We performed a retrospective
      review of 500 medical records of MS patients from the outpatients service of AISM
      Rehabilitation Centre, Genova, Italy. PATIENTS: All records of outpatients
      followed by AISM Rehabilitation Centre who underwent physical therapy from 2006
      to 2008 were evaluated. METHODS: Modified Fatigue Impact Scale (MFIS) and
      Ambulation Index (AI) were reviewed for all records at the begin and at the end
      of the rehabilitation treatment. RESULTS: The number of assessments recorded was
      295 in 209 patients. Out of the 209 patients, 133 were female and 76 were male.
      The mean age was 51.6 +/- 11.68 years, the mean Expanded Disability Status Scale
      (EDSS) score was 4.98 +/- 1.79, and 185 patients were ambulatory. In
      nonambulatory patients neither scale showed a significant increase. In ambulatory
      patients (275 assessments) significant changes were observed in AI, MFIS total
      score and subscores. CONCLUSION: Physical therapy has a positive impact on
      fatigue, and the MFIS seems to be a good outcome measure in ambulatory patients.
      The AI and MFIS seem to be not indicated for use in non-ambulatory patients.

PMID- 23949039
TI  - Relationship between self-reported walking ability and objectively assessed gait
      performance in persons with late effects of polio.
AB  - BACKGROUND: Muscle weakness in the lower limbs and impeded gait performance are
      common in persons with late effects of polio. OBJECTIVE: To assess self-reported
      walking ability in persons with late effects of polio and determine the
      relationship with objectively assessed gait performance. METHODS: One-hundred and
      twenty-two individuals with prior polio (65 women and 57 men, mean age 65 [SD +/-
      9] years) participated in the study. The main outcome measures were: Walk-12
      (Swedish version) to assess self-reported walking ability, and Timed "Up & Go",
      Comfortable Gait Speed, Fast Gait Speed and 6-Minute Walk Tests to assess gait
      performance objectively. RESULTS: More than 50% of the participants reported
      limitations (moderately or quite a bit) related to standing or walking, climbing
      stairs, walking speed and distance, concentration and effort, and gait quality
      aspects. Half of the participants reported no need to use support when walking
      indoors or outdoors, but 58% reported that their ability to run was extremely
      limited. Significant correlations (P < 0.01) were found between the Walk-12 and
      the four gait performance tests (rho -0.66 to 0.63). CONCLUSION: The strength of
      the relationship implies that Walk-12 reflects broader dimensions than the
      objective gait performance tests and can be a complement when the walking ability
      in persons with late effects of polio is evaluated.

PMID- 23949040
TI  - Exercise-onset heart rate increase is slowed in multiple sclerosis patients: does
      a disturbed cardiac autonomic control affect exercise tolerance?
AB  - OBJECTIVE: To explore the etiology of exercise intolerance in patients with MS,
      it is analyzed whether a disturbed cardiac autonomic control could be observed
      during exercise testing in patients with MS, and is related to exercise
      tolerance. PATIENTS AND METHOD: From 26 MS patients and 15 healthy subjects,
      exercise-onset (first 20 and 60 seconds) and -offset (1-minute recovery) HR
      change was determined during a 6-minute constant-load exercise bout on bike.
      Blood lactate, HR, oxygen uptake, expiratory volume and perceived exertion were
      assessed during exercise, and compared between groups. In 15 MS patients, a 6-min
      walking test was executed. RESULT: Twenty-second exercise-onset HR increase was
      significantly smaller in MS patients (14 +/- 7 bts/min) vs. healthy subjects (20
      +/- 8 bts/min, p < 0.05), and independently related to MS and age in total group
      (p < 0.05). Sixty-second exercise-onset and -offset HR changes were not different
      between groups, nor independently related to MS presence (p > 0.05). A
      significant correlation was found between 20-second exercise-onset HR increase
      and walking capacity in MS patients (r = 0.64, p < 0.01). CONCLUSION: In MS
      patients, the early increase in heart rate during endurance exercise is
      significantly slowed, indicating a disturbed cardiac autonomic control, and is
      related to exercise tolerance.

PMID- 23949041
TI  - Differences in current amplitude evoking leg extension in individuals with spinal
      cord injury.
AB  - OBJECTIVES: To investigate the effects of regional thigh composition that result
      in different responses to current amplitude among individuals with spinal cord
      injury (SCI) during applications of surface neuromuscular electrical stimulation
      (NMES) to evoke dynamic leg extension. DESIGN: Cross-sectional. SETTINGS:
      Academic Settings. METHODS: Five males with chronic motor complete SCI completed
      3 visits of NMES to determine the current amplitude required to evoke full knee
      extension. The participants underwent magnetic resonance imaging of both thighs
      to measure skeletal muscle cross-sectional area (CSA), thigh subcutaneous adipose
      tissue (SAT) and intramuscular fat (IMF). Applicants were classified into high (n
      = 3) and low-responders (n = 2) based on the determined current amplitude.
      RESULTS: The low-responders required 48-59% greater current amplitude to complete
      the same task as the high-responders. Low-responders had greater thigh SAT CSA
      (51-56%) than the high-responders with SCI. After adjusting to whole thigh CSA,
      IMF CSA was significantly greater in the low- responders; whereas skeletal muscle
      CSA was lower compared to the high-responders. CONCLUSION: The findings suggest
      that thigh SAT and IMF act as insulation against propagation of current during
      surface NMES applications in individuals with SCI.

PMID- 23949042
TI  - The effects of closed and open kinetic chain exercises on lower limb muscle
      activity and balance in stroke survivors.
AB  - OBJECTIVE: The major contributors to physical disability after stroke are the
      negative impairments related to loss of functional ability and muscle strength.
      The aim of this study was to examine the effects of close kinetic chain (CKC)
      exercise and open kinetic chain (OKC) exercise on muscle activation of the
      paretic lower limb and balance in chronic stroke subjects. METHODS: Thirty-three
      patients with chronic stroke of over 6 months were enrolled. They were randomly
      allocated to three groups: CKC exercise group (n = 11), OKC exercise group (n =
      11), and control group (n = 11). CKC and OKC exercise groups were trained 5 times
      per week for 6 weeks. The control group maintained routine activities and did not
      participate in any regular exercise program. All subjects were measured on muscle
      activation of the paretic lower limb and balance. RESULTS: Muscle activation of
      rectus femoris (RF) and biceps femoris (BF) was significantly increased in both
      CKC exercise and OKC exercise groups, compared to the control group. However,
      muscle activation of gastrocnemius (GC) and tibialis anterior (TA) was
      significantly increased in only the CKC exercise group. Antero-posterior (A-P)
      andmedio-lateral (M-L) sway velocities (both with EO and EC) were decreased with
      the application of CKC exercise. CONCLUSION: These findings indicate that the CKC
      exercise can improve lower limb muscle strength, and balance in chronic stroke,
      and it may carry over into an improvement in functional performance.

PMID- 23949043
TI  - Three upper limb robotic devices for stroke rehabilitation: a review and clinical
      perspective.
AB  - BACKGROUND: Stroke is a leading cause of disability worldwide. Many survivors of
      stroke remain with residual disabilities, even years later. Advances in
      technology have led to the development of a variety of robotic devices for use in
      rehabilitation. The integration of robotics in the delivery of
      neurorehabilitation is promising, but still not widely used in clinical settings.
      OBJECTIVES: The aim of this review is to discuss the general design of three
      typical upper limb robotic devices, and examine the practical considerations for
      their use in a clinical environment. METHODS: Each device is described, the
      available clinical literature is reviewed and a clinical perspective is given on
      the usefulness of these robotic devices in rehabilitation of this population.
      RESULTS: Current literature supports the use of robotics in the clinical
      environment. However, claims that robotic therapy is more effective than
      traditional treatment is not substantially supported. The majority of clinical
      trials reported are small, and lack the use of a control group for comparison
      treatment. CONCLUSIONS: The use of robotics in stroke rehabilitation is still a
      relatively new treatment platform, and still evolving. As technological advances
      are made, there is much potential for growth in this field.

PMID- 23949044
TI  - Correlations among impairment, daily activities and thinking operations after
      stroke.
AB  - OBJECTIVES: We investigated the hypothesis that ADL tests dependent on cortical
      functions could be used to assess outcome in stroke patients. MATERIALS AND
      METHOD: 27 right-handed stroke patients were evaluated on National Institute of
      Health Stroke Scale (NIHSS), Barthel Index (BI), Instrumental Activities of Daily
      Living (IADL) Scale and thinking process items of Lowenstein Occupational Therapy
      Cognitive Assessment (LOTCA). RESULTS: Correlations between thinking process
      subtests of LOTCA and different items of NIHSS such as consciousness, arm
      movement, aphasia, ataxia and inattention was significant. Spearman correlation
      of thinking process and BI tasks showed no relationship, although Structured
      Riska of thinking process evaluation was correlated to both self-care and
      mobility areas of the BI. Thinking process was strongly related to IADL total
      score (p = 0.004). The total NIHSS correlated significantly with BI and IADL
      total scores. CONCLUSION: Higher-order functions, such as categorization, sorting
      and reasoning, are related to IADL performance which depends on complicated
      cognitive abilities. In contrast, the BI depends heavily on motoric function, and
      does not correlate with higher-order functions. Further confirmation is needed,
      but our data suggest that commonly used IADL tests could serve to as valid,
      reliable tests of cognitive impairment and recovery in stroke victims.

PMID- 23949045
TI  - Clinical application of a modular ankle robot for stroke rehabilitation.
AB  - BACKGROUND: Advances in our understanding of neuroplasticity and motor learning
      post-stroke are now being leveraged with the use of robotics technology to
      enhance physical rehabilitation strategies. Major advances have been made with
      upper extremity robotics, which have been tested for efficacy in multi-site
      trials across the subacute and chronic phases of stroke. In contrast, use of
      lower extremity robotics to promote locomotor re-learning has been more recent
      and presents unique challenges by virtue of the complex multi-segmental mechanics
      of gait. OBJECTIVES: Here we review a programmatic effort to develop and apply
      the concept of joint-specific modular robotics to the paretic ankle as a means to
      improve underlying impairments in distal motor control that may have a
      significant impact on gait biomechanics and balance. METHODS: An impedance
      controlled ankle robot module (anklebot) is described as a platform to test the
      idea that a modular approach can be used to modify training and measure the time
      profile of treatment response. RESULTS: Pilot studies using seated visuomotor
      anklebot training with chronic patients are reviewed, along with results from
      initial efforts to evaluate the anklebot's utility as a clinical tool for
      assessing intrinsic ankle stiffness. The review includes a brief discussion of
      future directions for using the seated anklebot training in the earliest phases
      of sub-acute therapy, and to incorporate neurophysiological measures of cerebro
      cortical activity as a means to reveal underlying mechanistic processes of motor
      learning and brain plasticity associated with robotic training. CONCLUSIONS:
      Finally we conclude with an initial control systems strategy for utilizing the
      anklebot as a gait training tool that includes integrating an Internal Model
      based adaptive controller to both accommodate individual deficit severities and
      adapt to changes in patient performance.

PMID- 23949046
TI  - Reliability of the Turkish version of the hospital anxiety and depression scale
      in the people with traumatic spinal cord injury.
AB  - BACKGROUND: Emotional problems are common in spinal cord injury (SCI). Self
      report questionnaires are easy and useful for screening the emotional status in
      clinical practice. OBJECTIVES: The aim of this study was to assess the
      reliability of the Turkish version of the Hospital Anxiety and Depression Scale
      (HADS) as well as to investigate the frequency of anxiety and depression in a
      group with SCI admitted to the outpatient clinic of a rehabilitation hospital.
      METHODS: One hundred seventy-five persons with traumatic SCI were included in
      this study. The American Spinal Injury Association Impairment Scale, Functional
      Independence Measure (FIM) and HADS were used for assessments. RESULTS: The mean
      age of the participants was 35 +/- 13 years, and the mean time elapsed since
      injury was 13 +/- 29 months. The mean motor FIM score was 41 +/- 21. The
      Cronbach's alpha coefficient was 0.90 and 0.77 for the anxiety and depression
      subscales of the HADS, respectively. Forty percent of the participants had
      anxiety and 28% had depression. Anxiety was positively correlated with time since
      injury (r = 0.2). Depression was negatively correlated with the education level
      (r = 0.25), and positively correlated with age (r = 0.17). There was a positive
      correlation with completeness and anxiety and depression (r = 0.49, r = 0.55).
      CONCLUSION: The Turkish version of the HADS is a reliable psychological screening
      test for anxiety and depression in people with SCI. Rehabilitation team should
      gather maximum information about the emotional status of the person with SCI, and
      plan the appropriate treatment for anxiety and depression.

PMID- 23949047
TI  - Motor recovery by improvement of limb-kinetic apraxia in a chronic stroke
      patient.
AB  - OBJECTIVES: We report on a chronic stroke patient who showed motor recovery by
      improvement of limb-kinetic apraxia (LKA) after undergoing intensive
      rehabilitation for a period of one month, which was demonstrated by diffusion
      tensor tractography (DTT) and transcranial magnetic stimulation (TMS). METHODS: A
      50-year-old male patient presented with severe paralysis of the left extremities
      at the onset of thalamic hemorrhage. At thirty months after onset, the patient
      exhibited moderate weakness of his left upper and lower extremities. In addition,
      he exhibited a slow, clumsy, and mutilated movement pattern during grasp-release
      movements of his left hand. During a one-month period of intensive
      rehabilitation, which was started at thrity months after onset, the patient
      showed 22% motor recovery of the left extremities. The slow, clumsy, and
      mutilated movement pattern of the left hand almost disappeared. RESULTS: DTTs of
      the corticospinal tract (CST) in both hemispheres originated from the cerebral
      cortex, including the primary motor cortex, and passed along the known CST
      pathway. The DTT of the right CST was located anterior to the old hemorrhagic
      lesion. TMS study performed at thirty and thirty-one months after onset showed
      normal and similar findings for motor evoked potential in terms of latency and
      amplitude of the left hand muscle. CONCLUSIONS: We think that the motor weakness
      of the left extremities in this patient was mainly ascribed to LKA and that most
      of the motor recovery during a one-month period of rehabilitation was attributed
      to improvement of LKA.

PMID- 23949048
TI  - Percutaneous endoscopic gastrostomy tube placement in left versus right middle
      cerebral artery stroke: effects of laterality.
AB  - BACKGROUND: Prolonged dysphagia after middle cerebral artery (MCA) territory
      strokes may require percutaneous endoscopic gastrostomy (PEG) tube feeding.
      OBJECTIVE: We examined the predictors of PEG placement among patients with MCA
      stroke. It was hypothesized that stroke laterality was a predictor. METHODS: A
      retrospective cohort study of existing data from Hartford Hospital Stroke
      Database was done. A total of 157 patients with acute ischemic MCA stroke were
      included. Patients were divided into the "PEG" group (n = 24) and "no PEG" group
      (n = 133). Existing demographic, clinical and swallowing data were compared
      between the 2 groups. RESULTS: Demographic data were similar between the groups.
      The "PEG" group had a higher admission National Institute of Health Stroke Scale
      (NIHSS) score, higher proportion of patients who had thrombolytic administration,
      in- hospital aspiration pneumonia and inability to be assessed on first swallow
      evaluation. Multivariate analysis revealed that all, except thrombolytic
      administration may predict PEG placement. CONCLUSION: Admission NIHSS score, in
      hospital aspiration pneumonia and inability to undergo first swallow evaluation
      may predict PEG placement in patients with acute MCA stroke. Stroke laterality
      was not associated. This knowledge facilitates early identification of patients
      that may require PEG tube placement for early nutrition provision and discharge
      to rehabilitation.

PMID- 23949049
TI  - Predictors of functional outcome in Saudi Arabian patients with stroke after
      inpatient rehabilitation.
AB  - PURPOSE: To identify the possible factors influencing functional outcome of
      stroke patients after inpatient rehabilitation. METHODS: One hundred and eighty
      patients with stroke consecutively admitted for inpatient stroke rehabilitation
      was studied. Demographic and stroke characteristics, impairment (National
      Institutes of Health Stroke Scale), disability level (Functional Independence
      Measure [FIM]), psycho-emotional state (Geriatric Depression Scale-15 [GDS-15]),
      cognitive function (Mini Mental State Evaluation [MMSE]), and preexisting medical
      conditions were recorded at admission. The main measure of functional outcome was
      the discharge FIM score. The univariate and multiple linear regression analyses
      were performed. RESULT: The Mean admission total FIM score was 64.8 +/- 22.4 and
      the mean discharge total FIM score was 84.0 +/- 23.0, with this gain being highly
      significant (P < 0.001). Univariate analyses indicated that the significant
      factors influencing functional outcome of stroke patients at discharge from
      rehabilitation included age, total FIM score at admission, severity of stroke,
      recurrent stroke, cognitive impairment, and depression. However, in multiple
      linear regression analyses, age was not significant predictor. CONCLUSION: Age
      predicts the function outcome to lesser extent than other covariate. The
      admission total FIM score, cognitive condition, depression, and stroke severity
      are predictors of functional outcome of stroke patients after inpatient
      rehabilitation.

PMID- 23949050
TI  - Effectiveness of an intensive rehabilitation treatment on different Parkinson's
      disease subtypes.
AB  - GOAL AND OBJECTIVES: Parkinsonian patients can be classified in two main
      subgroups: tremor dominant and akinetic-rigid. The aim of this study was to
      evaluate whether intensive rehabilitation treatment has the same efficacy in the
      two subtypes. MATERIAL AND METHODS: Patients were classified according to tremor:
      65 patients with absence of tremor in "on" and "off" state were assigned to
      Group_1 and 65 patients with tremor were assigned to Group_2. All patients
      underwent a 4-week intensive multidisciplinary rehabilitation treatment. The
      primary outcome measures were: the Unified Parkinson's Disease Rating Scale
      (UPDRS) II, III, UPDRS akinetic-rigid score and UPDRS tremor score. The secondary
      outcome measures were: the Berg Balance Scale, 6-minute walking test, self
      assessment Parkinson's Disease Disability Scale, Abnormal Involuntary Movement
      Scale, Freezing of Gait Questionnaire. RESULTS: Patients in Group_1 tended to be
      more affected than patients in Group_2 by dyskinesias (45% vs 29% p = 0.069) and
      freezing (46% vs 29%, p = 0.046). Levodopa-equivalent dosages were higher in
      Group_1 (802 vs 670 mg/day, p = 0.008). Considering the effect of rehabilitation,
      an homogeneous improvement was observed in all variables in both groups of
      patients (p < 0.0001). CONCLUSION: Intensive rehabilitation treatment is
      effective in improving motor performance in both groups. The anatomical and
      biochemical differences existing between the two subgroups appear to not
      determine different clinical outcomes.

PMID- 23949051
TI  - Relationship between lower extremity isometric muscle strength and standing
      balance in patients with multiple sclerosis.
AB  - BACKGROUND: Muscle strength and standing balance decrease in patients with
      Multiple Sclerosis (MS). OBJECTIVE: The aim of the present study was to
      investigate the relationship between the lower extremity isometric muscle
      strength and standing balance in patients with MS. METHODS: Forty-seven patients
      with MS and 10 healthy volunteers were included. Neurological disability level
      was assessed using Expanded Disability Status Scale (EDSS). Isometric strength of
      seven lower extremity muscles (hip flexor-extensor-abductor-adductor, knee flexor
      extensor, and ankle dorsal flexor) was assessed using hand-held dynamometer.
      Duration of static one-leg standing balance was measured using digital
      chronometer. RESULTS: Hip flexor-extensor-abductor-adductor, knee flexor
      extensor, and ankle dorsal flexor isometric muscle strength, and duration of one
      leg standing balance were decreased in patients with MS when compared with
      controls (p < 0.05). All assessed lower extremity isometric muscle strength and
      EDSS level was related duration of one-leg standing balance in patients with MS.
      All assessed lower extremity isometric muscle strength (except ankle dorsal
      flexor) was related with EDSS. CONCLUSIONS: Hip flexor-extensor-abductor
      adductor, knee flexor-extensor, and ankle dorsal flexor isometric muscle strength
      decreases in ambulatory MS patients. Lower extremity muscle weakness and
      neurological disability level are related with imbalance in MS population. Hip
      and knee region muscles weakness increases the neurological disability level. For
      the better balance and decrease neurological disability level whole lower
      extremity muscle strengthening should be included in rehabilitation programs.

PMID- 23949052
TI  - Predictors of long-term recovery in complex activities of daily living before
      discharge from the stroke unit.
AB  - BACKGROUND AND PURPOSE: There is a need for individuating those post-stroke
      patients who may benefit from an optimal and customised rehabilitation plan
      aiming at early reintegration in community life participation. This study
      investigated whether the gain of independence in complex Activities of Daily
      Living (ADL) may be predicted before the discharge from the stroke unit using
      simple bedside determinants. METHODS: In 104 first-ever stroke patients with no
      previous disability, ten determinants at 10 days after stroke were selected.
      Multivariable logistic regression analysis was applied to identify the prognostic
      determinants able to predict independence in complex ADL, as measured by modified
      Rankin Scale grade <=2. RESULTS: The model shows that having a Barthel Index >=9,
      a Motricity Index- Upper Limb >=75, an age <=70 and being a male resulted in 100%
      probability of achieving independence in complex ADL. If three of the four
      determinants were present, the probability was more than 90%. With the presence
      of two of the four determinants, the probability ranged from 87% to 28%. With the
      presence of only one determinant, the probability was 13%. CONCLUSIONS: Accurate
      prediction of independence in complex ADL can be made before the discharge from
      the stroke unit. The strength of the paretic upper limb, age, gender, and the
      ability of performing basic ADL are the significant variables. The probability of
      favorable prognosis depends on the presence and on the robustness of each single
      determinant.

PMID- 23949053
TI  - Selective use of low frequency stimulation in Parkinson's disease based on
      absence of tremor.
AB  - BACKGROUND: High frequency stimulation (HFS) of the subthalamic nucleus is one of
      the most effective treatments for advanced Parkinson's disease (PD). HFS has
      provided beneficial improvements in the cardinal features of PD, but has not been
      proven as effective for addressing the axial predominant levodopa resistant
      symptoms, such as speech disturbances, gait disturbances, and postural
      instability. Recent studies have suggested that changes in stimulation parameters
      may influence differing PD symptoms. OBJECTIVE: The purpose of this study was to
      compare the effects of low frequency stimulation (LFS) versus HFS on the Unified
      Parkinson's Disease Rating Scale (UPDRS), gait, balance, and verbal fluency.
      METHODS: Eight tremor dominant and nine non-tremor dominant participants with
      bilateral deep brain stimulation of the subthalamic nucleus were tested off
      stimulation, during LFS, and during HFS. RESULTS: Results revealed that HFS
      significantly reduced UPDRS tremor score in the tremor dominant group; however no
      differences emerged within the non-tremor dominant group. No differences between
      groups or stimulation conditions were found for gait, balance, and verbal fluency
      measures. CONCLUSION: These results may suggest that HFS is better than LFS for
      reducing tremor in tremor dominant patients. However, patients with mild or no
      tremor show no acute differences in benefit from LFS as compared to HFS.

PMID- 23949054
TI  - Effects of robotic treadmill training on functional mobility, walking capacity,
      motor symptoms and quality of life in ambulatory patients with Parkinson's
      disease: a preliminary prospective longitudinal study.
AB  - BACKGROUND: Decreased mobility and walking capacity occur frequently in
      Parkinson's disease (PD). Robotic treadmill training is a novel method to improve
      the walking capacity in rehabilitation. OBJECTIVES: The primary aim of this study
      was to investigate the effects of robotic treadmill training on functional
      mobility and walking capacity in PD. Secondly, we aimed to assess the effects of
      the robotic treadmill training the motor symptoms and quality of life in patients
      with PD. METHODS: Seventy patients with idiopathic Parkinson's disease who
      admitted to the outpatient clinic of the rehabilitation hospital were screened
      and 12 ambulatory volenteers who met the study criteria were included in this
      study. Patients were evaluated by Hoehn Yahr (HY) scale clinically. Two sessions
      robotic treadmill training per week during 5 weeks was planned for every patient.
      Patients were evaluated by the Timed Up and Go (TUG) test, 10 meter walking test
      (10 MWT), Unified Parkinson's Disease Rating Scale (UPDRS) motor section and
      Parkinson's Disease Questionnaire-39 (PDQ-39) at the baseline, at the 5 and 12
      weeks. Cognitive and emotional states of the patients were assessed by Mini
      Mental State Examination (MMSE) test and Hospital Anxiety and Depression Scale
      (HADS) at the baseline. All patients were under medical treatment for the PD in
      this study and drug treatment was not changed during the study. RESULTS: Ten
      patients completed the study. The mean age was 65.6 +/- 6.6 years. Five patients
      (50%) were women. Disease severity was between the HY stage 1-3. Two patients did
      not continue the robotic treadmill training after 7 sessions. They also did not
      want to come for control visits. TUG test, 10 MWT and UPDRS motor subscale scores
      showed statistically significant improvement after robotic treadmill training (p
      = 0.02, p = 0.001, p = 0.016). PDQ-39 scores improved significantly after robotic
      treadmill training (p = 0.03), however, the scores turned back to the baseline
      level at the 12. week control. CONCLUSION: As a result of this preliminary study,
      robotic treadmill training was useful to improve the functional mobility, walking
      capacity and motor symptoms in mild to moderate PD. Robotic treadmill training
      provided a transient improvement in the quality of life during the treatment.

PMID- 23949055
TI  - Lower urinary tract dysfunction in critical illness polyneuropathy.
AB  - BACKGROUND: Critical illness polyneuropathy is a frequent complication of
      critical illness in intensive care units. Reports on autonomic systems like lower
      urinary tract and bowel functions in patients with CIP are not available in
      medical literature. OBJECTIVE: This study performed during primary rehabilitation
      of patients with critical illness polyneuropathy explores if sensory and motor
      pathways controlling the lower urinary tract function are affected from the
      disease. METHODS: Neurourological examinations, urodynamics, electromyography and
      lower urinary tract imaging were performed in 28 patients with critical illness
      polyneuropathy. DISCUSSION: Sacral sensation was impaired in 1 patient (4%).
      Sacral reflexes were absent in 8 patients (30%). Anal sphincter resting tone was
      reduced in 3 (12%), anal sphincter voluntary contraction was absent or reduced in
      8 patients (30%). Urodynamic findings were detrusor overactivity and detrusor
      overactivity incontinence in 9 (37.5%), incomplete voiding in 8 (30%), abnormal
      sphincter activity in 4 (16%), abnormal bladder sensation in 4 (16%) and detrusor
      acontractility in 2 patients (8.3%). Morphological abnormalities of the lower
      urinary tract had 10 patients (41.6%). CONCLUSION: Sensory and motor pathways
      controlling the lower urinary tract might be affected from CIP. During
      urodynamics dysfunctions of the storage as well as the voiding phase were found.
      Morphological lower urinary tract abnormalities were common.

PMID- 23949056
TI  - Neuropsychological and neuroanatomical sequelae of chronic non-malignant pain and
      opioid analgesia.
AB  - BACKGROUND: The pervasive disease of chronic pain is a common challenge for the
      clinical rehabilitation professional. Concurrent with physical and emotional
      symptoms, pain-related cognitive impairment has been reported. Although opioid
      analgesics are frequently prescribed, concern exists that opioids possess adverse
      cognitive effects of their own. OBJECTIVES: To review the neuropsychological and
      neuroanatomical sequelae of chronic non-malignant pain and opioid therapy, to
      clarify roles and benefits of neuropsychological assessment in a chronic pain
      population, and to provide recommendations for clinical practice and future
      research. METHODS: This non-systematic review sought to provide a comprehensive
      synthesis of relevant neurobiology, neuroimaging, neuropsychological, and
      rehabilitation research literatures. We included citations from seminal and
      current texts as well as relevant original and review articles from 1980-2012 in
      PubMed and PubMedCentral online research databases. DISCUSSION AND
      SUMMARY/CONCLUSIONS: To date, evidence from opioid studies suggests only mild
      deficits in specific cognitive domains (e.g., memory, attention/concentration)
      and only under specific conditions (e.g., dose escalations). Additionally,
      neuroimaging and neuropsychological evidence suggests that pain itself results in
      cognitive sequelae. Methodological improvements in future research will allow for
      better delineation of the contributing effects of pain and opioids, with an
      overall goal of improving evidence-based clinical treatment recommendations.

PMID- 23949057
TI  - Repeated sessions of functional repetitive transcranial magnetic stimulation
      increases motor cortex excitability and motor control in survivors of stroke.
AB  - OBJECTIVE: To determine the impact of a single-session of repetitive transcranial
      magnetic stimulation (rTMS) and an rTMS intervention on neurophysiology and motor
      control in survivors of stroke. METHODS: Twelve stroke survivors were randomized
      into functional-rTMS or passive-rTMS conditions. Measures of short-interval
      intracortical inhibition (SICI) and intracortical facilitation (ICF), and force
      steadiness (coefficient of variation, CV) at 10 and 20% of maximum voluntary
      contraction were assessed at baseline and after a single-session of rTMS (post
      single-session), and again following an intervention of 8 rTMS sessions (2
      sessions per day; post-intervention). Functional-rTMS required subjects to exceed
      a muscle activation threshold assessed by surface electromyography to trigger
      each rTMS train; the passive-rTMS group received rTMS while relaxed. RESULTS: ICF
      scores significantly increased following the single-session of functional-rTMS
      compared to the decrease following passive-rTMS. The increase in APB SICI and ICF
      scores following the intervention was significantly greater for the functional
      rTMS group compared to the decreases following passive-rTMS. The groups were
      significantly different in the CV of force (20%) following the single-session of
      rTMS, and in the 10 and 20% tasks following the intervention. The functional-rTMS
      group increased steadiness overtime, whereas the passive group demonstrated a
      return to baseline following the intervention session. No differences were
      observed in first dorsal interosseus (FDI) measures (SICI and ICF) between
      groups. CONCLUSIONS: The functional-rTMS protocol enhanced cortical excitability
      following a single-session and after repeated sessions and improved steadiness,
      whereas the passive stimulation protocol tended to decrease excitation and no
      improvements in steadiness were observed.

PMID- 23949058
TI  - Tolerance and effectiveness of a new dynamic hand-wrist orthosis in chronic
      stroke patients.
AB  - PURPOSE: To evaluate tolerance of a new dynamic hand-wrist orthosis and
      effectiveness on the prevention of progressive wrist contracture and spasticity
      after stroke. METHOD: Chronic stroke patients (N = 6) with upper limb spasticity,
      who had not been able to endure a static orthosis, were provided with a custom
      made dynamic orthosis. Tolerance of the orthosis was evaluated by the daily
      wearing time, and self-reported pain and spasticity. Effectiveness was measured
      by contracture of wrist and finger flexor muscles, upper limb spasticity and use
      of spasticity treatment. Outcome measures were collected at time of fitting of
      the dynamic orthosis (baseline) and after three and six months. RESULTS: Five
      patients could endure the dynamic orthosis without discomfort for 6 hours daily
      during the 6-month period. Self-reported spasticity and pain decreased
      significantly (p < 0.05) compared to wearing the static orthosis. In comparison
      to baseline, the maximum passive wrist extension increased significantly from -29
      degrees  to -12 degrees  (p < 0.05). Although, no significant change in
      spasticity was measured, the use of Botulinum Toxin injections decreased for two
      patients. CONCLUSIONS: The majority of the included chronic stroke patients
      tolerated the new dynamic orthosis for at least 6 hours daily and the use
      significantly reduced wrist contractures in a 6-month period.

PMID- 23949059
TI  - Perceptions of stroke recovery: an exclusion of communication and cognition.
AB  - BACKGROUND: Perceptions of stroke recovery can differ substantially between
      stroke survivors and their healthcare providers. Concordance between the two is
      important for collaborative goal setting to facilitate optimal outcomes.
      OBJECTIVE: To explore stroke survivors' perceptions of their own recovery and
      residual impairments with specific emphasis on communication and cognition.
      METHODS AND PROCEDURES: A qualitative analytic approach was used in the study.
      Nine stroke survivors participated in a focus group discussion as part of a
      larger study designed to examine post-stroke outcomes. RESULTS: Early in the
      focus group proceedings, a discussion emphasizing how stroke survivors perceive
      their overall recovery emerged. Six of the nine participants (67%) perceived
      their overall stroke recovery to be greater than 90%, and only physical
      impairments were reported. Later in the course of the interview, eight of the
      nine participants (89%) reported either word retrieval or memory loss deficits
      which negatively influenced their daily functional activities. CONCLUSIONS:
      Stroke survivors in this sample did not include communication and cognitive
      deficits in their perception of their overall recovery despite later reporting
      these symptoms and related impairment. Failure of patients to include such
      persisting deficits in their reports of recovery can cause a mismatch between
      stroke survivor and provider goals.

PMID- 23949060
TI  - Recovery of injured cingulum in a patient with brain injury: diffusion tensor
      tractography study.
AB  - OBJECTIVES: Little is known about neural recovery of an injured cingulum
      following brain injury. We report on a patient with brain injury who showed
      apparent neural recovery of an injured cingulum on follow up diffusion tensor
      tractography (DTT). METHODS: A 53-year-old female patient had suffered hypoxic
      ischemic brain injury for a period of approximately nine hours following
      spontaneous subarachnoid hemorrhage and intraventricular hemorrhage, and
      underwent coiling of a left ruptured aneurysm of the posterior communicating
      artery. She showed severe cognitive impairment, so that she could not be
      evaluated on the Mini-Mental State Examination, however, her cognition showed
      improvement to 21 at five months after onset and 24 at 14 months after onset on
      the Mini-Mental State Examination. RESULTS: On seven-day DTT for the fornix in
      the patient, we observed a discontinuation in the left crus and thinning of the
      right crus. However, on 14-month DTT, the thinned right fornical crus had
      disappeared. Regarding the cingulum, on seven-day DTTs, discontinuations of both
      cingulums anterior to the genu of the corpus callosum were observed. However, on
      14-month follow up DTT, the right cingulum was elongated to the right basal
      forebrain and no change in the discontinuation of the left cingulum was observed.
      CONCLUSIONS: These changes observed on DTT in both cingulums appeared to indicate
      recovery of the injured cingulum in this patient. The results of this study may
      suggest a mechanism for recovery of injured cingulum following brain injury.

PMID- 23949061
TI  - Psychometric properties of the German version of the health-related quality of
      life in stroke patients (HRQOLISP) instrument.
AB  - OBJECTIVE: There is lack of a German-language holistic stroke-specific health
      related quality of life (HRQOL) measure with therapeutically-oriented domains.
      The objective of this study was to investigate the psychometric properties of the
      HRQOL in stroke patients (HRQOLISP) questionnaire in German stroke survivors.
      METHODS: Following standard procedure for cross-cultural validation, the HRQOLISP
      was translated into German. It was completed by 103 German stroke patients and 50
      apparently healthy controls. Acceptance, ceiling and floor effects, reliability,
      as well as content, construct, factorial and known-group's validity were
      analysed. Stratification was according to modified Rankin, stroke levity and
      National Institute of Health stroke scales. RESULTS: The HRQOLISP was acceptable
      and holistic with neither ceiling nor floor effect. One-factor solution explained
      >40% of the variance for most domains. Two-factor solution explained 82% of the
      variance for the global HRQOL consistent with the conceptual framework
      distributing the therapeutically-oriented domains into two spheres. Cronbach's
      alpha ranged from 0.77 to 0.92 for the domains. The HRQOLISP, though lengthy,
      covered the entire spectrum of stroke-related HRQOL with no additional item
      suggested by the German stroke patients. The HRQOLISP demonstrated good
      convergent and discriminant validity as well as excellent 'known groups' validity
      across disability and stroke severity strata. CONCLUSIONS: The German version of
      the HRQOLISP is the first holistic, stroke-specific HRQOLISP measures with
      therapeutically-oriented domains to be validated in Germany. It is acceptable,
      reliable and valid but needs to be validated in proxies to facilitate its utility
      among stroke patients with severe communication problems.

PMID- 23949062
TI  - Social behaviour following severe traumatic brain injury: contribution of emotion
      perception deficits.
AB  - OBJECTIVE: This theoretically driven study aimed to determine contribution of
      emotional perception impairments to social behaviour following traumatic brain
      injury (TBI). METHODS: Adults with severe TBI (n = 24) participated. Emotion
      perception predictors included: (i) appraisal: Montreal Set of Facial Displays of
      Emotion, The Adapted Story Task, (ii) affective state: Depression, Anxiety and
      Stress Scale (DASS-21), Interpersonal Reactivity Index (IRI) and (iii)
      regulation: Delis Kaplan Executive Function System - Colour Word Interference and
      Word Fluency. Social behavioural outcomes were (i) interpersonal: Key Behaviors
      Change Inventory (KBCI) - Interpersonal Difficulties and (ii) communication: KBCI
      - Communication Problems. RESULTS: Social behaviours correlated with affective
      state, but not appraisal or regulation. Simultaneous regression analyses revealed
      significant independent contributions of affective state: (i) the IRI Perspective
      Taking to the KBCI Interpersonal Difficulties and (ii) the DASS-21 (composite)
      and IRI Perspective Taking to the KBCI Communication Problems. The models
      explained 52% and 72% of the variance of the KBCI Interpersonal Difficulties and
      Communication Problems respectively. CONCLUSIONS: This study provides evidence
      that impairments in certain aspects of emotion perception: affective state
      [empathy (perspective taking) and mood], but not appraisal and regulation,
      contribute to social behaviour difficulties in patients with severe TBI, which
      has important implications for rehabilitation.

PMID- 23949063
TI  - Benefits of inpatient multidisciplinary rehabilitation in multiple sclerosis.
AB  - BACKGROUND: Rehabilitation is often recommended to MS-patients but data on its
      efficacy is limited. OBJECTIVE: To evaluate the benefit of inpatient
      multidisciplinary rehabilitation. METHODS: A rater-blinded, randomized, waiting
      list controlled exploratory study. 19 participants completed the study with ten
      allocated to the intervention and nine to the waiting list group. Assessment of
      outcome-parameters was done at baseline and after 3 months. Time Walking Tests
      (TWTs) and 9 Hole Peg Test were used to objectively assess the level of activity,
      Functional-Assessment-in-MS and MS-Self Efficacy-Scale to assess participation
      and quality of life and Expanded Disability Status Scale (EDSS) to assess bodily
      function. Additionally Rivermead Mobility Index, Berg Balance Scale, Tinetti
      Test, MS-Functional Composite and a rater-blinded evaluation of a video-analysis
      on walking performance was done. RESULTS: Mean change scores of Timed 50 meter
      Walk (p = 0.014), walking speed (p = 0.034), 2- (p = 0.204) and 6-Minute Walk (p
      = 0.027) indicated an improvement favoring inpatient multidisciplinary
      rehabilitation. We could not demonstrate a benefit for upper limb function and
      some improvement was seen in other outcome-parameters without reaching
      statistical significance. EDSS remained unchanged. CONCLUSION: Inpatient
      multidisciplinary rehabilitation is effective in MS patients with positive impact
      on the level of activity as measured by TWTs covering both short and long
      distance ambulation.

PMID- 23949064
TI  - The effects of pilates on balance, mobility and strength in patients with
      multiple sclerosis.
AB  - BACKGROUND: Although there are evidences as to Pilates developing dynamic
      balance, muscle strength and flexibility in healthy people, evidences related to
      its effects on Multiple Sclerosis patients are insufficient. OBJECTIVES: The aims
      of this study were to investigate the effects of Pilates on balance, mobility,
      and strength in ambulatory patients with Multiple Sclerosis. METHODS: Twenty six
      patients were divided into two groups as experimental (n = 18) and control (n =
      8) groups for an 8-week treatment program. The experimental group underwent
      Pilates and the control group did abdominal breathing and active extremity
      exercises at home. Balance and mobility were measured with Berg Balance Scale and
      Timed up and go test, upper and lower muscle strength with hand-held dynamometer.
      Confidence in balance skills while performing daily activities was evaluated with
      Activities Specific Balance Confidence Scale. RESULTS: Improvements were observed
      in balance, mobility, and upper and lower extremity muscle strength in the
      Pilates group (p < 0.05). No significant differences in any outcome measures were
      observed in the control group (p > 0.05). CONCLUSION: Due to its structure which
      is made up of balance and strengthening exercises, Pilates training may develop
      balance, mobility and muscle strength of MS patients. For this reason, we think
      that, Pilates exercises which are appropriate for the disability level of the
      patient may be suggested.

PMID- 23949065
TI  - Using multiple views of family dynamics to predict the mental health of
      individuals with TBI and their caregivers in Mexico.
AB  - PURPOSE: To examine differences in ratings of family dynamics between individuals
      with traumatic brain injury (TBI) and their family caregivers in Mexico, as well
      as differences in the prediction of caregiver and patient mental health outcomes
      from those ratings. METHOD: Forty-two patient-caregiver dyads (n = 84) from the
      National Institute of Rehabilitation in Mexico City participated in a
      comprehensive evaluation of their family dynamics and mental health. RESULTS:
      Patients' and caregivers' ratings of family dynamics were significantly
      correlated and did not differ across five of six types of family dynamics, but
      caregivers rated their family's level of empathy higher than patients, p < 0.001.
      Additionally, all patient and caregiver ratings of family dynamics were
      significantly correlated. Patients', caregivers', and combined (using structural
      equation modeling latent constructs) ratings of family dynamics robustly
      predicted four times as many caregiver mental health outcomes as patient mental
      health outcomes. CONCLUSIONS: Family dynamics influence both TBI patient and
      caregiver mental health but much more so in caregivers. Research on families of
      individuals with TBI in Mexico should incorporate both patient and caregiver
      perspectives to more comprehensively depict the environment in which TBI
      rehabilitation occurs.

PMID- 23949066
TI  - Biomechanical muscle stimulation and active-assisted cycling improves active
      range of motion in individuals with Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a neurological disorder which often
      results in joint rigidity, bradykinesia and decreased range of motion (ROM).
      Segmental biomechanical muscle stimulation (BMS) can increase ROM in healthy
      young adults. However, acute effects on ROM in PD have not been examined.
      OBJECTIVE: To examine whether BMS and active-assisted cycling (AAC) of the legs
      results in acute changes in ROM in PD. METHODS: Seventeen individuals with PD
      completed four sessions. Subjects first came to the lab 'on' PD medications and
      completed baseline assessments. During session 2, subjects were 'off' PD
      medications and watched a video describing the interventions. In the 3rd and 4th
      visits, subjects were 'off' medications and the order of AAC or BMS was
      counterbalanced. Shoulder and hip ROM was measured prior to and immediately after
      each intervention and hip kinematics were examined during over-ground walking.
      RESULTS: There was a significant improvement in hip and shoulder ROM after BMS
      and AAC. Hip velocity during over-ground walking improved after BMS but not after
      AAC. CONCLUSIONS: Single bouts of BMS and AAC have a positive effect on ROM and
      hip velocity during over-ground walking. This suggests that BMS and AAC may be
      altering central motor control processes.

PMID- 23949067
TI  - Visual stimulations' critical period in infants with perinatal brain damage.
AB  - BACKGROUND: Children with perinatal brain damage have a high prevalence of visual
      impairment. Stimulation of vision at a critical period can encourage brain
      plasticity and the recovery of impaired function. OBJECTIVE: The aim of our study
      was to investigate when is the critical period for visual stimulation in children
      with perinatal brain damage. METHODS: We compared 35 children within the first
      eight months of life (median age = 4 months) to 35 children aged between eight
      and thirty months (median age = 15 months), all with perinatal brain damage. All
      the children were attending an early intervention program at Mali dom, Zagreb, a
      rehabilitation centre for children with visual impairment. We compared the
      results from baseline and follow-up assessments of visual functions (grating
      acuity and contrast sensitivity). We also compared differences in change scores
      between the two groups. RESULTS: Our results have shown that children who
      commence a visual stimulation program within the first eight months of life had
      more improvement in both visual functions. This improvement is statistically
      significant in visual acuity (p = 0.048). CONCLUSIONS: These results indicate the
      importance of starting a visual stimulation program within the first eight months
      after birth.

PMID- 23949068
TI  - The effect of protein and calorie intake on prealbumin, complications, length of
      stay, and function in the acute rehabilitation inpatient with stroke.
AB  - BACKGROUND: Nutrition's impact on stroke rehabilitation outcomes is
      controversial. Existing studies utilize albumin without correcting for
      inflammation in nutritional assessments. Here, prealbumin was used and
      inflammation assessed to determine if nutrition impacts rehabilitation outcomes.
      OBJECTIVE: Determine the effect of dietary intake on prealbumin level, number of
      complications, length of stay, and Functional Independence Measure (FIM)
      efficiency in rehabilitation stroke inpatients. METHODS: Patients had admission
      and discharge prealbumin and C-reactive protein (CRP) levels drawn; and, weekly
      protein and calorie counts obtained. Patients were followed for number of
      complications, length of stay, and FIM efficiency. RESULTS: Mean protein and
      calorie intake was 57.6 +/- 16.2 g/d and 1452.2 +/- 435.8 kcal/d, respectively.
      77.6% of patients had normal prealbumin on admission with 94.9% on discharge.
      Prealbumin increased significantly from admission to discharge (22.3 +/- 6.2
      mg/dL vs. 24.6 mg/dL +/- 5.1 mg/dL, P = 0.007). Number of complications and
      length of stay were predicted by CRP in regression models. Total, motor, and
      cognitive FIM efficiencies were not universally affected by prealbumin levels,
      protein intake, or calorie intake. CONCLUSIONS: Nearly all hypoprealbuminemic
      stroke rehabilitation inpatients correct their levels eating a non-supplemented
      diet. Number of complications, length of stay, and functional outcomes in this
      patient are not affected by prealbumin levels, protein intake, or calorie intake.

PMID- 23949069
TI  - Behavioral physiotherapy in post stroke rehabilitation.
AB  - INTRODUCTION: Behavioral aspects of motor learning such as definition and
      assessment of patient-centered goals, specific motivation, training in the
      patients' environment, autonomous training and generalization of newly learned
      skills to daily life are not an explicit part of physiotherapy in
      neurorehabilitation. BEHAVIORAL PHYSIOTHERAPY: Specific goals are defined and
      applied in a step by step manner. Exercises and application in daily life were
      trained and anticipated as a "self control cue" for the following week.
      Motivation was sustained via supervision, feedback after successful trials and
      reward. Exercises have to occure at a daily basis and have to be implemented in
      everyday life. CASE DESCRIPTION: A 54 year old man who suffered cerebral bleeding
      with left hemiparesis 25 years ago. We report goal attainment, change of symptoms
      and walking capacities over a period of 18 months. RESULTS: Back pain and knee
      pain reduced to zero, rhythmic walking, walking speed increased, left leg less
      resistance, running possible. DISCUSSION: The here described principles of
      behavioral physiotherapy are crucial for successful outcome in extremely stable
      and persistent consequences of stroke. Studies with more patients are needed to
      strengthen our hypothesis.

PMID- 23949070
TI  - A hippotherapy simulator is effective to shift weight bearing toward the affected
      side during gait in patients with stroke.
AB  - AIM: We investigated whether a hippotherapy simulator has influence on symmetric
      body weight bearing during gait in patients with stroke. METHOD: Stroke patients
      were divided into a control group (n = 10) that received conventional
      rehabilitation for 60 min/day, 5 times/week for 4 weeks and an experimental group
      (n = 10) that used a hippotherapy simulator for 15 min/day, 5 times/week for 4
      weeks after conventional rehabilitation for 45 min/day. Temporospatial gait
      assessed using OptoGait and trunk muscles (abdominis and erector spinae on
      affected side) activity evaluated using surface electromyography during sit-to
      stand and gait. Prior to starting the experiment, pre-testing was performed. At
      the end of the 4-week intervention, we performed post-testing. RESULT: Activation
      of the erector spinae in the experimental group was significantly increased
      compared to that in the control group (p < 0.01), whereas activation of the
      rectus abdominis decreased during sit-to-stand. Of the gait parameters, load
      response, single support, total double support, and pre-swing showed significant
      changes in the experimental group with a hippotherapy simulator compared to
      control group (p < 0.05). Moreover, activation of the erector spinae and rectus
      abdominis in gait correlate with changes of gait parameters including load
      response, single support, total double support, and pre-swing in experimental
      group. CONCLUSION: These findings suggest that use of a hippotherapy simulator to
      patients with stroke can improve asymmetric weight bearing by influencing trunk
      muscles.

PMID- 23949071
TI  - Effect of continuing repeated passive and active exercises on knee's position
      senses in patients with hemiplegia.
AB  - OBJECTIVE: To determine the repeated passive movement (RPM) and repeated active
      movement (RAM) exercise on position sense of the knee joint in patients with
      hemiplegia. METHODS: 45 hemiplegia patients were randomly allocated to either the
      control group(no exercise), RPM group, or RAM group, with 15 subjects in each
      group. The exercise was repeated 60 times on the angle 10 to 100 degrees of the
      knee joint with an angle speed of 120 degrees /s, with three sets for 15 minutes.
      Evaluation was performed using Passive Angle Repositioning (PAR) and Active Angle
      Repositioning (AAR). RESULTS: Error of positioning sense showed a decrease in PAR
      and AAR in the RPM group (p < 0.01) and an increase in AAR was observed in the
      RAM group (p < 0.05). In comparison of knee joint position sense error value and
      rate of change among the three groups, the RPM group is decreased mostly in PAR
      and AAR (p < 0.01), and Error value (p < 0.05) and rate of change (p < 0.01) of
      the RAM group showed a greater increase in AAR than the control group.
      CONCLUSION: RAM exercise can support an increase in proprioception on the knee
      joint of hemiplegia; however, RAM exercise that causes fatigue can decrease
      proprioception.

PMID- 23949072
TI  - Do motor impairments detected on onset of multiple sclerosis suggest an early
      second attack? A prospective study.
AB  - BACKGROUND: Factors determining the clinically isolated syndrome (CIS) patient's
      likelihood of developing multiple sclerosis (MS) are important for the clinician
      who needs to identify patients warranting immunomodulatory treatments. OBJECTIVE:
      To determine whether motor abnormalities found during the initial demyelinating
      event imply an increased risk of a second event within the first year. METHODS:
      Fifty-two early onset CIS patients, volunteered to participate in the prospective
      study. Motor parameters collected at onset included gait, balance, lower limb
      peak isometric strength and fatigue index parameters. At the end of one year,
      patients were subdivided into two groups, those who had experienced a second
      demyelinating attack suggestive of MS and those who maintained their clinical
      status. RESULTS: Forty-nine patients were included in the final analysis. Within
      the first year, 24 patients experienced a second attack, while 25 maintained
      their neurological status. Patients who suffered a second demyelinating attack,
      demonstrated reduced overall lower limb peak strength compared with patients who
      maintained their clinical status (411.9 (S.E. = 32.1) vs. 514.8 (S.E. = 34.1). No
      differences were observed between groups in gait and balance parameters.
      CONCLUSION: An initial demyelinating event characterized by reduced lower limb
      strength can possibly suggest an increased risk of an early second attack.

PMID- 23949073
TI  - Validity and responsiveness of the German version of the Motor Activity Log for
      the assessment of self-perceived arm use in hemiplegia after stroke.
AB  - BACKGROUND: Rehabilitation of patients after stroke requires valid and responsive
      assessments for arm and hand function to determine the effectiveness of
      rehabilitative interventions. The Motor Activity Log (MAL) aims to assess self
      perceived arm and hand use after stroke. Its clinimetric properties are
      incomplete and contradictory. OBJECTIVE: To investigate internal consistency,
      concurrent validity and responsiveness of the German MAL-30 in patients after
      stroke with minimal to moderate arm and hand function. METHODS: 42 patients were
      included in this longitudinal prospective cohort study. Internal consistency was
      determined in a complete-case analysis with Cronbach's alpha. Concurrent validity
      was assessed with Spearman' rho by comparing the German MAL-30 with Wolf Motor
      Function Test, Chedoke McMaster Stroke Assessment, isometric elbow, shoulder and
      grip strength at baseline, post-treatment and 6 month follow-up. Responsiveness
      was determined separately for lower and higher arm and hand function by
      calculating the standardized response mean. RESULTS: Internal consistency was
      excellent (Cronbach's alpha = 0.94-0.99), concurrent validity good to excellent
      (Spearman's rho = 0.64-0.99). Responsiveness was high for both functional levels
      from baseline to discharge (SRM = 0.93-1.43) and to follow-up (SRM = 0.95-1.34).
      CONCLUSION: The German MAL-30 is a valid and responsive assessment for self
      perceived arm and hand use after stroke even when function is low.

PMID- 23949074
TI  - Effects of Ai-Chi on balance, functional mobility, strength and fatigue in
      patients with multiple sclerosis: a pilot study.
AB  - BACKGROUND: Multiple Sclerosis (MS) patients are often referred to aquatic
      physical therapy, but unfortunately, researches on the effects of aquatic therapy
      in MS patients are limited. OBJECTIVE: The purpose of this study was to
      investigate the effects of Ai-Chi on balance, functional mobility, strength and
      fatigue in ambulatory patients with MS. METHODS: Twenty-three ambulatory female
      patients were divided into two groups as experimental (n = 15) or control (n = 8)
      for an 8-week treatment program. The experimental group underwent Ai-Chi
      exercises in a swimming pool and the control group performed active arm and leg
      exercises combined with abdominal breathing exercises at home. Static standing
      balance was measured with duration of one-leg stance, functional mobility was
      evaluated with Timed-up and Go test and 6 minute walk test, upper and lower
      muscle strength was assessed with hand-held dynamometer and fatigue was evaluated
      with Fatigue Severity Scale. RESULTS: Improvements were observed in static
      standing balance, functional mobility, upper and lower extremity muscle strength
      and fatigue in the Ai-Chi group (p < 0.05), but no significant differences in any
      outcome measures were observed in the control group (p > 0.05) after the
      intervention. CONCLUSIONS: According to these findings Ai-Chi may improve
      balance, functional mobility, upper and lower extremity muscle strength and
      fatigue in patients with MS.

PMID- 23949075
TI  - Effects of an 1-day education program on physical functioning, activity and
      quality of life in community living persons with multiple sclerosis.
AB  - BACKGROUND: Persons with MS (pwMS) in the community show reduced physical
      activity while studies demonstrated beneficial effects of exercise therapy in
      supervised settings. OBJECTIVE: This study investigated, in pwMS living in the
      community, the effects of a 1-day education program about exercises and sports,
      on physical activity behavior and related outcome measures as self-efficacy,
      perceived walking ability, fatigue, perceived impact of MS and quality of life.
      METHODS: PwMS attended an education day with theoretical and practical sessions
      that was organized by the Flemish MS Society and professional exercise experts.
      Forty-two participants immediately completed questionnaires as well as after
      three and six months. Overall disability and physical activity level were
      measured using PDSS (patient determined disease steps) and PASIPD (Physical
      Activity Scale for Individuals with Physical Disabilities) respectively. Other
      outcomes were the ESES, MSWS-12, MFIS, MSIS-29 and SF-36. Analyses of variance
      were performed in groups distinguished by self-reported disability level (PDDS
      <=1; n = 24 and PDSS >1; n = 18). RESULTS: Groups differed significantly for
      perceived walking ability (PDDS,MSWS-12) and physical related-domains of MSIS-29
      and SF-36, but not PASIPD. A trend towards significant group*time interaction
      effect was found for the PASIPD indicating, at 3 and 6 months, increased physical
      activity in the subgroup PDDS <=1. For the MSIS-29, a significant time effect was
      found with reduced impact being largest for the more disabled group at 6 months.
      No changes were found in other outcome measures. CONCLUSION: An one-day education
      program had, depending on perceived disability level, some long-standing effects
      on physical activity and perceived impact of MS.

PMID- 23949077
TI  - A comparison of health behaviors between African Americans with spinal cord
      injury and those in the general population.
AB  - OBJECTIVE: The purpose of this study is to identify whether protective and risk
      health behaviors are more common among African Americans with spinal cord injury
      (SCI) compared with African Americans in the general population. METHODS: Mail-in
      surveys were collected from 252 adult participants with SCI. Behavioral Risk
      Factor Surveillance System data from 2009 was downloaded. RESULTS: Participants
      with SCI were more likely to report currently smoking. Among those who reported
      currently smoking, persons with SCI were less likely to report ever trying to
      quit. Those with SCI were also more likely to report consuming alcohol and binge
      drinking in the past month. Participants with SCI were more likely to receive a
      flu shot/spray in the past year and to have ever received a pneumonia vaccine.
      Conversely, those with SCI were less likely to report ever having their blood
      cholesterol checked. CONCLUSIONS: Results of this study suggest that, consistent
      with previous research, individuals with SCI focused their preventive health
      behaviors on conditions consistent with SCI prophylactic standard of care (e.g.,
      flu shots and pneumonia vaccines), as compared to behaviors intended to prevent
      chronic diseases consistent with the overall population.

PMID- 23949078
TI  - Hydrocephalus following severe traumatic brain injury in adults. Incidence,
      timing, and clinical predictors during rehabilitation.
AB  - OBJECTIVE: To investigate timing and clinical predictors that might predict
      hydrocephalus emerging during rehabilitation until 1 year following severe
      traumatic brain injury (TBI). BACKGROUND: Posttraumatic hydrocephalus (PTH) may
      lead to clinical deterioration and poor outcome if untreated. However, PTH can be
      successfully treated if detected. Nevertheless, PTH is easily overlooked during
      rehabilitation, particularly in severe cases. METHOD: We prospectively followed
      all patients (n = 444) in Eastern Denmark (population 2.5 mill) sustaining severe
      TBI, who required lengthy rehabilitation between 2000 and 2010. All patients with
      PTH were tracked retrospectively. Demographics, surgery, injury severity,
      consciousness level, and disability were compared for patients with versus
      without PTH. Independent predictors of PTH during rehabilitation were identified
      through multiple logistic regression models. RESULTS: PTH occurred in 14.2% and
      3/4 emerged during rehabilitation. Patients with PTH were older, had more severe
      brain injuries, were more frequently in vegetative state, and needed longer
      rehabilitation stays. After adjusted analyses, however, only older age and low
      level of consciousness were independently associated with PTH. CONCLUSION: Most
      cases of PTH emerge during rehabilitation. Therefore, attention towards this
      complication should be present also beyond the acute stage after TBI,
      particularly among older patients and patients with severe disordered
      consciousness.

PMID- 23949079
TI  - A feasibility study using interactive graphic art feedback to augment acute
      neurorehabilitation therapy.
AB  - BACKGROUND: Interactive arts technologies, designed to augment the acute
      neurorehabilitation provided by expert therapists, may overcome existing barriers
      of access for patients with low motor and cognitive function. OBJECTIVES: Develop
      an application prototype to present movement feedback interactively and
      creatively. Evaluate feasibility of use within acute neurorehabilitation.
      METHODS: Record demographics and Functional Independent MeasureTM scores among
      inpatients who used the technology during physical, occupational or recreational
      therapy. Record exercises performed with the technology, longest exercise
      duration performed (calculated from sensor data), user feedback, and therapist
      responses to a validated technology assessment questionnaire. RESULTS: Inpatients
      (n = 21) between the ages of 19 and 86 (mean 57 +/- 18; 12 male/9 female)
      receiving treatment for motor deficits associated with neuropathology used the
      application in conjunction with occupational, recreational, or physical therapy
      during 1 to 7 sessions. Patients classified on the Functional Independence
      MeasureTM as requiring 75%+ assistance for cognitive and motor function were able
      to use the interactive application. CONCLUSIONS: Customized interactive arts
      applications are appropriate for further study as a therapeutic modality. In
      addition to providing interactivity to individuals with low motor function,
      interactive arts applications might serve to augment activity-based medicine
      among inpatients with low problem-solving and memory function.

PMID- 23949080
TI  - Long-term cortical reorganization following stroke in a single subject with
      severe motor impairment.
AB  - BACKGROUND: Stroke continues to be a major public health concern in the United
      States. Motor recovery in the post-acute stages of stroke is possible due to
      neuroplasticity, or the capacity of the brain to reorganize. OBJECTIVE: This case
      study tracks neuroplastic and motor change in a subject with severe hemiparesis
      following an extensive middle cerebral artery stroke. He had absence of
      ipsilesional motor evoked potentials in early evaluations. This report is unique
      in that the duration of follow-up evaluation extends nearly 2 years, with
      evaluations being performed at 7, 9, 10, 13, 20, and 21 months post-stroke.
      METHODS: At each evaluation we used transcranial magnetic stimulation to track
      neuroplastic change and the Fugl-Meyer Assessment and the Wolf Motor Function
      Test to evaluate upper extremity motor performance. RESULTS: The contralesional
      hemisphere showed dynamic change throughout the study period. In contrast, the
      ipsilesional hemisphere demonstrated notable change only between 13 and 21 months
      post-stroke, with the most dramatic change occurring between 20 and 21 months
      post-stroke. Motor performance generally improved throughout the study period.
      CONCLUSIONS: Our findings demonstrate that substantial neuroplasticity-mediated
      motor recovery can occur nearly 2 years after stroke in an individual with severe
      post-stroke motor impairment.

PMID- 23949081
TI  - Extracorporeal Shock Wave Therapy reduces upper limb spasticity and improves
      motricity in patients with chronic hemiplegia: a case series.
AB  - BACKGROUND: Extracorporeal Shock Wave Therapy (ESWT) has been proposed for
      treatment of abnormal muscle tone only in the last years. The effects on motor
      impairment are unknown. OBJECTIVE: To assess the long-term effects of ESWT on
      muscle tone and motricity in upper limb in patients with chronic hemiplegia.
      METHODS: Twelve patients were selected and treated with two sessions of ESWT.
      Participants were assessed at baseline, after the treatment, and at 3 and 6
      months. Muscle tone of shoulder adductors, elbow, wrist and finger flexors was
      evaluated at all assessment points using the Modified Ashworth Scale (MAS), while
      motricity, passive range of motion (PROM) and pain sub-scores of upper extremity
      part of the Fugl-Meyer scale were used to assess motor recovery. The degree of
      perceived benefit from treatment was assessed on a visual analogue scale.
      RESULTS: MAS showed a significant reduction of spasticity and Fugl-Meyer scores
      improved immediately after treatment. Persistent effects were observed at 3 and 6
      months for MAS, and for motricity and PROM subscores of the Fugl-Meyer scale.
      Clinical improvement was not correlated to the patients' perceived benefit.
      CONCLUSIONS: Two sessions of ESWT seem to have long-term effects in reducing
      muscle tone and enhancing motor impairment.

PMID- 23949082
TI  - Relation between cingulum injury and cognition in chronic patients with traumatic
      brain injury; diffusion tensor tractography study.
AB  - OBJECTIVES: Many diffusion tensor imaging (DTI) studies have reported an
      association between cingulum injury and cognition in patients with traumatic
      brain injury (TBI) using DTI parameters. In this study, we attempted to
      investigate the relation between cingulum injury and cognition in chronic
      patients with TBI, using the integrity of the cingulum as well as DTI parameters.
      METHOD: Thirty five consecutive chronic patients with TBI were recruited. The
      intelligence quotient (IQ) of the Wechsler Intelligence Scale and Memory
      Assessment Scale (MAS) was used for assessment of cognition. The patients were
      classified into three groups, according to continuity to the lower portion of the
      genu of the corpus callosum: type A-both sides of the cingulum showed intact
      continuity, type B-either cingulum showed a discontinuation, and, type C-both
      cingulums showed discontinuation. We measured the fractional anisotropy (FA),
      apparent diffusion coefficient (ADC), and voxel number of both cingulums.
      RESULTS: The IQ and MAS scores of type A and B were significantly higher than
      those of type C, respectively (p < 0.05), however, we did not observe a
      significant difference between type A and type B (p > 0.05). A positive
      correlation was observed between the FA value of the cingulum, and IQ and MAS,
      respectively (IQ r = 0.373, p < 0.05, MAS r = 0.357, p < 0.05), and between the
      voxel number and MAS (r = 0.500, p < 0.05). By contrast, we observed a negative
      correlation between the ADC value and IQ (r = -0.353, p < 0.05). CONCLUSION: In
      terms of integrity to the basal forebrain and DTI parameters of the injured
      cingulum, DTI findings showed a close association with whole cognition and memory
      in chronic patients with TBI.

PMID- 23949083
TI  - Muscle synergies with Walkaround(r) postural support vs. "cane/therapist"
      assistance.
AB  - BACKGROUND: The main clinical measures of walking recovery in stroke patients
      were compared for training assisted by Walkaround(r) postural support (WPS) and
      conventional (CON) support by a cane/therapist. OBJECTIVE: We attributed the
      differences between the trainings to modified muscular synergies that occurred
      during assistance by WPS. METHODS: We studied the muscle activities of the
      primary knee and ankle joint movers in the paretic and non-paretic legs of sub
      acute stroke patients during assisted walking with WPS and CON. Recorded signals
      were compared to normative data that were recorded during speed-matched gait
      trials in healthy subjects. The specific measures were the relative contribution
      of individual muscles, levels of cocontraction, and the timing of the maximum
      electromyography (EMG) activity during the walking sessions. RESULTS: We found
      that, for most patients, the individual contribution of muscles were more similar
      to the healthy with the WPS assistance. In parallel, the cocontraction of the
      rectus femoris muscles in both legs was lower (by up to 39 %) during walking
      assisted by WPS than by cane/therapist gait support); the results from this case
      series (10 patients) showed that WPS might be the superior training scheme.
      CONCLUSIONS: These findings indicated that assistance by WPS changed the motor
      control output relative to CON assistance in most patients.

PMID- 23949084
TI  - Muscle strength is only a weak to moderate predictor of gait performance in
      persons with late effects of polio.
AB  - OBJECTIVE: To assess muscle strength in the knee extensors, knee flexors and
      ankle dorsiflexors in persons with late effects of polio, and determine how much
      muscle strength, gender, age and BMI are related to gait performance. METHODS:
      Ninety community-dwelling ambulant persons (47 men and 43 women; mean age 64
      years SD 8) with late effects of polio participated. Isokinetic concentric knee
      extensor and flexor muscle strength was measured at 60 degrees /s and ankle
      dorsiflexor muscle strength at 30 degrees /s. Gait performance was assessed by
      the Timed "Up & Go", the Comfortable and Fast Gait Speed tests, and the 6-Minute
      Walk test. RESULTS: There were significant correlations between knee extensor and
      flexor muscle strength and gait performance (p < 0.01), and between ankle
      dorsiflexor muscle strength and gait performance (p < 0.05), for both lower
      limbs. Muscle strength in the knee extensors and flexors explained 7% to 37% and
      9% to 47%, respectively, of the variance in gait performance. Strength in the
      ankle dorsiflexors explained 4% to 24%, whereas gender, age and BMI contributed
      at most an additional 9%. CONCLUSION: Knee muscle strength, and to some extent
      ankle dorsiflexor muscle strength, are predictors of gait performance in persons
      with late effects of polio, but the strength of the relationships indicates that
      other factors are also important.

PMID- 23949085
TI  - Thermodynamic behaviour of supercritical matter.
AB  - Since their discovery in 1822, supercritical fluids have been of enduring
      interest and have started to be deployed in many important applications.
      Theoretical understanding of the supercritical state is lacking and is seen to
      limit further industrial deployment. Here we study thermodynamic properties of
      the supercritical state and discover that specific heat shows a crossover between
      two different regimes, an unexpected result in view of currently perceived
      homogeneity of supercritical state in terms of physical properties. We
      subsequently formulate a theory of system thermodynamics above the crossover, and
      find good agreement between calculated and experimental specific heat with no
      free-fitting parameters. In this theory, energy and heat capacity are governed by
      the minimal length of the longitudinal mode in the system only, and do not
      explicitly depend on system-specific structure and interactions. We derive a
      power law and analyse supercritical scaling exponents in the system above the
      Frenkel line. 

PMID- 23949086
TI  - Phenethyl isothiocyanate induces apoptosis of cholangiocarcinoma cells through
      interruption of glutathione and mitochondrial pathway.
AB  - Phenethyl isothiocyanate (PEITC) is a natural isothiocyanate with anticancer
      activity against many drug-resistant cancer cells. A body of evidence suggests
      that PEITC enhances oxidative stress leading to cancer cell death.
      Cholangiocarcinoma (CCA) is an aggressive bile duct cancer with resistance to
      chemotherapeutic drugs. PEITC rapidly kills KKU-100 CCA cells with concurrent
      induction of cellular glutathione depletion, superoxide formation, and loss of
      mitochondrial transmembrane potential. The loss was associated with increased Bax
      and decreased Bcl-xl proteins followed by the release of cytochrome c and the
      activation of caspase-9 and -3. Although TEMPOL could prevent superoxide
      formation, it did not prevent the disruption of glutathione (GSH) redox,
      mitochondrial dysfunction, and cell death. On the other hand, N-acetylcysteine
      could prevent the events and cell death. It was concluded that disruption of GSH
      redox but not superoxide formation may be an initial step leading to
      mitochondrial injury. PEITC could be a promising chemopreventive agent for CCA. 

PMID- 23949088
TI  - Metal loading determines the stabilization pathway for Co2+ in titanate
      nanowires: ion exchange vs. cluster formation.
AB  - Co nanoparticles were produced and characterized on protonated titanate
      nanowires. Co deposits were obtained after low-temperature decomposition of
      Co2(CO)8 on titanate nanostructures. The carbonylation was carried out by vapor
      phase adsorption in a fluidized bed reactor and the decarbonylation processes
      were followed by FT-IR spectroscopy and microbalance combined with temperature
      programmed reaction mass spectrometry. The band gap of Co-decorated titanate
      nanostructures determined by UV-VIS diffuse reflectance spectroscopy decreased
      sharply from 3.14 eV to 2.41 eV with increasing Co content up to 2 wt%. The Co
      decorated titanate morphology was characterized by high-resolution transmission
      electron microscopy (HRTEM) and electron diffraction (ED). The chemical
      environment of Co deposition was studied by photoelectron spectroscopy (XPS). A
      certain amount of cobalt underwent an ion exchange process. Higher cobalt
      loadings led to the formation of nanosized-dispersed particles complexed to
      oxygen vacancies. The average sizes were found to be mostly between 2 and 6 nm.
      This size distribution and the measured band gap could be favorable regimes for
      some important low-temperature thermal- and photo-induced catalytic reactions. 

PMID- 23949087
TI  - Differential mechanism of the effects of ester-type local anesthetics on
      sarcoplasmic reticulum Ca-ATPase.
AB  - The effect of the local anesthetics procaine and tetracaine on sarcoplasmic
      reticulum membranes isolated from two masticatory muscles, masseter and medial
      pterygoid, was tested and compared to fast-twitch muscles. The effects of the
      anesthetics on Ca-ATPase activity, calcium binding, uptake, and phosphorylation
      of the enzyme by inorganic phosphate (Pi) were tested with radioisotopic methods.
      Calcium binding to the Ca-ATPase was non-competitively inhibited, and the
      enzymatic activity decreased in a concentration-dependent manner. The inhibition
      of the activity depended on pH, calcium concentration, the presence of the
      calcium ionophore calcimycin, and the membrane protein concentration. Unlike fast
      twitch membranes, the pre-exposure of the masseter and medial pterygoid membranes
      to the anesthetics enhanced the enzymatic activity in the absence of calcimycin,
      supporting their permeabilizing effect. Procaine and tetracaine also interfered
      with the calcium transport capability, decreasing the maximal uptake without
      modification of the calcium affinity for the ATPase. Besides, the anesthetics
      inhibited the phosphorylation of the enzyme by Pi in a competitive manner.
      Tetracaine revealed a higher inhibitory potency on Ca-ATPase compared to
      procaine, and the inhibitory concentrations were lower than usual clinical doses.
      It is concluded that procaine and tetracaine not only affect key steps of the Ca
      ATPase enzymatic cycle but also exert an indirect effect on membrane permeability
      to calcium and suggest that the consequent myoplasmic calcium increase induced by
      the anesthetics might account for myotoxic effects, such as sustained contraction
      and eventual rigidity of both fast-twitch and masticatory muscles.

PMID- 23949089
TI  - Preoperative estimated glomerular filtration rate as a significant predictor of
      long-term outcomes after coronary artery bypass grafting in Japanese patients.
AB  - PURPOSES: The aim of this retrospective study was to investigate the effect of
      chronic kidney disease (CKD) on outcomes after coronary artery bypass grafting
      (CABG), and to determine whether preoperative estimated glomerular filtration
      rate (eGFR) can be a predictor of long-term outcomes after CABG. METHODS: 486
      Japanese patients who underwent isolated CABG between December 2000 and August
      2010 were evaluated. Preoperative eGFR was estimated by the Japanese equation
      according to guidelines from the Japanese Society of Nephrology. We defined CKD
      as a preoperative eGFR of less than 60 ml/min/1.73 m(2). 203 patients had CKD (CK
      group) and 283 patients did not (N group). RESULTS: During a mean observation
      time of 53 months, the overall survival rate was significantly lower in the CK
      group than in the N group (p = 0.0044). Similarly, the CK group had significantly
      more unfavorable results with regard to freedom from cardiac death, major adverse
      cardiovascular and cerebrovascular events (MACCE), and hemodialysis. Using
      multivariate analyses, preoperative eGFR was an independent predictor of all
      cause mortality (HR 0.983; p = 0.026), cardiac mortality (HR 0.963; p = 0.006),
      and incidence of MACCE (HR 0.983; p = 0.002). CONCLUSIONS: The CK group had
      significantly more unfavorable outcomes than the N group. Preoperative eGFR was
      an independent predictor of long-term outcomes after CABG in Japanese patients.

PMID- 23949090
TI  - Phrenic nerve paralysis from recurrence of stage I thymoma with myasthenia gravis
      10 years after complete resection.
AB  - A 34-year-old woman underwent thymo-thymectomy for myasthenia gravis (MG) and was
      diagnosed with type B3 Masaoka stage I thymoma. Phrenic nerve paralysis developed
      8 years after surgery, and a left-sided mediastinal mass was seen on a chest
      radiograph 10 years after surgery. Chest computed tomography revealed a tumor
      measuring 57 * 21 * 28 mm beside the aortic arch. Surgical resection of the tumor
      with partial resection of phrenic and recurrent nerve, the left upper lobe, and
      the pericardium was performed through a left thoracotomy. Histological
      examination confirmed recurrent thymoma invading the resected surrounding organs.
      The patient received radiation therapy postoperatively and was alive with stable
      symptoms of MG at the 2-year follow-up. Symptomatic relapse of thymoma is very
      rare and an occult recurrent thymoma should be considered in patients with
      unilateral phrenic nerve paralysis even after complete resection of thymoma.
      Detailed examination with careful follow-up should be considered.

PMID- 23949091
TI  - Redox-active charge carriers of conducting polymers as a tuner of conductivity
      and its potential window.
AB  - Electric conductivity of conducting polymers has been steadily enhanced towards a
      level worthy of being called its alias, "synthetic metal". PEDOT:PSS (poly(3,4
      ethylenedioxythiophene) doped with poly(styrene sulfonate)), as a representative
      conducting polymer, recently reached around 3,000 S cm(-1), the value to open the
      possibility to replace transparent conductive oxides. The leading strategy to
      drive the conductivity increase is solvent annealing in which aqueous solution of
      PEDOT:PSS is treated with an assistant solvent such as DMSO (dimethyl sulfoxide).
      In addition to the conductivity enhancement, we found that the potential range in
      which PEDOT:PSS is conductive is tuned wider into a negative potential direction
      by the DMSO-annealing. Also, the increase in a redox-active fraction of charge
      carriers is proposed to be responsible for the enhancement of conductivity in the
      solvent annealing process.

PMID- 23949092
TI  - Reply to letter to the editor on: Boomerang proximal tibial osteotomy for the
      treatment of severe varus gonarthrosis.

PMID- 23949093
TI  - Did you notice the tibial nutrient artery when applying external fixation?

PMID- 23949094
TI  - False negative newborn screen and neonatal cholestasis in a premature child with
      cystic fibrosis.
AB  - Newborn screening for cystic fibrosis enables early diagnosis and treatment,
      leading to better outcomes for patients with cystic fibrosis. Although the
      sensitivity of several screening protocols is high, false negative screening
      results of the newborn patient still occur, which can lead to a significant delay
      in diagnosis when the awareness for presenting symptoms of cystic fibrosis
      declines. Neonatal cholestasis is one of the presenting symptoms of cystic
      fibrosis but can be easily missed when total parenteral nutrition has been given.
      Premature newborns are probably more at risk of a missed underlying diagnosis
      than term babies because their co-pathologies and management are often more
      complex. We present a case of a 10-week-old premature boy with a false negative
      newborn screening for cystic fibrosis, in whom cystic fibrosis presented with
      neonatal cholestasis. In this case, the immunoreactive trypsinogen/pancreatitis
      associated protein/35 cystic fibrosis transmembrane regulator mutation
      analysis/sequencing method was used. Furthermore, an overview of the literature
      on missed diagnosis of cystic fibrosis due to a false negative newborn screen is
      provided. CONCLUSION: Cystic fibrosis (CF) should be considered in infants with
      neonatal cholestasis even when the newborn screening for CF is reported to be
      negative.

PMID- 23949095
TI  - Evaluations of the selectivities of the diacylglycerol kinase inhibitors R59022
      and R59949 among diacylglycerol kinase isozymes using a new non-radioactive assay
      method.
AB  - Ten mammalian diacylglycerol kinase (DGK) isozymes (alpha-kappa) have been
      identified. Recent studies have revealed that DGK isozymes play pivotal roles in
      a wide variety of pathophysiological functions. Thus, it is important to be able
      to easily check DGK activity in each pathophysiological event. Moreover, the
      conventional DGK assay is quite laborious because it requires the use of a
      radioisotope and thin-layer chromatography including multiple extraction steps.
      In order to minimize the laborious procedures, we established a non-radioactive,
      single well, two-step DGK assay system. We demonstrated that, compared to the
      conventional method, the new assay system has comparable sensitivity and much
      higher efficiency, and is effective in detecting potential agents with high
      reliability (Z'-factor = 0.69 +/- 0.12; n = 3). Using the newly developed assay,
      we comprehensively evaluated the DGK isozyme selectivities of commercially
      available DGK inhibitors, R59022 and R59949, in vitro. We found that among 10
      isozymes, R59022 strongly inhibited type I DGKalpha and moderately attenuated
      type III DGKepsilon and type V DGKtheta, and that R59949 strongly inhibited type
      I DGK alpha and gamma, and moderately attenuated type II DGK delta and kappa. 

PMID- 23949096
TI  - Development and validation of the Dry Eye-Related Quality-of-Life Score
      questionnaire.
AB  - IMPORTANCE: A validated questionnaire that assesses symptoms and the effect of
      dry eye disease (DED) on the patient's daily life is needed to evaluate the
      condition. OBJECTIVE: To develop and validate the Dry Eye-Related Quality-of-Life
      Score (DEQS) questionnaire in Japan. DESIGN, SETTING, AND PARTICIPANTS:
      Development and evaluation of the DEQS questionnaire were conducted in 4 phases:
      (1) item generation, (2) pilot study to assess content and face validity, (3)
      preliminary psychometric validation study to examine factor structure and reduce
      the number of items, and (4) final psychometric validation with 224 participants
      (203 with DED and 21 serving as controls). Participants completed the DEQS
      questionnaire, the Short Form-8, and the National Eye Institute Visual Function
      Questionnaire-25. To evaluate reproducibility and responsiveness, individuals
      with DED completed the DEQS questionnaire twice. MAIN OUTCOMES AND MEASURES:
      Internal consistency, reproducibility, discriminant validity, concurrent
      validity, and responsiveness. RESULTS: Items were generated from a literature
      review, and 35 items were selected for the draft version. In the pilot study, 11
      items were deleted; furthermore, 9 items were deleted based on the results of
      item analysis and factor analysis in the preliminary validation study. The final
      15-item DEQS questionnaire consisted of an Overall Summary scale and 2 multi-item
      subscales: Impact on Daily Life and Bothersome Ocular Symptoms. The psychometric
      analysis revealed that the DEQS questionnaire has good internal consistency, test
      retest reliability, discriminant validity, and responsiveness to change. The DEQS
      questionnaire correlated well with the mental component of the Short Form-8 and
      showed strong correlations with 4 subscales (Ocular Pain, Near Vision, Distance
      Vision, and Mental Health) of the National Eye Institute Visual Function
      Questionnaire-25. CONCLUSIONS AND RELEVANCE: The DEQS questionnaire is valid and
      reliable for evaluating the multifaceted effect of DED on the patient's daily
      life, including mental health, and it can be used easily in routine clinical
      practice.

PMID- 23949097
TI  - Fructose-maltodextrin ratio governs exogenous and other CHO oxidation and
      performance.
AB  - INTRODUCTION: Fructose coingested with glucose in carbohydrate (CHO) drinks
      increases exogenous-CHO oxidation, gut comfort, and physical performance.
      PURPOSE: This study aimed to determine the effect of different fructose
      maltodextrin-glucose ratios on CHO oxidation and fluid absorption while
      controlling for osmolality and caloricity. METHODS: In a crossover design, 12
      male cyclists rode 2 h at 57% peak power then performed 10 sprints while
      ingesting artificially sweetened water or three equiosmotic 11.25% CHO-salt
      drinks at 200 mL.15 min, comprising weighed fructose and maltodextrin-glucose in
      ratios of 0.5:1 (0.5 ratio), 0.8:1 (0.8 ratio), and 1.25:1 (1.25 ratio). Fluid
      absorption was traced with D2O, whereas C-fructose and C-maltodextrin-glucose
      permitted fructose and glucose oxidation rate evaluation. RESULTS: The mean
      exogenous-fructose and exogenous-glucose oxidation rates were 0.27, 0.39, and
      0.46 g.min and 0.65, 0.71, and 0.58 g.min in 0.5, 0.8, and 1.25 ratio drinks,
      representing mean oxidation efficiencies of 54%, 59%, and 55% and 65%, 85%, and
      86% for fructose and glucose, respectively. With the 0.8 ratio drink, total
      exogenous-CHO oxidation rate was 18% (90% confidence interval, +/-5%) and 5.2%
      (+/-4.6%) higher relative to 0.5 and 1.25 ratios, respectively, whereas
      respective differences in total exogenous-CHO oxidation efficiency were 17% (+/
      5%) and 5.3% (+/-4.8%), associated with 8.6% and 7.8% (+/-4.2%) higher fructose
      oxidation efficiency. The effects of CHO ratio on water absorption were
      inconclusive. Mean sprint power with the 0.8 ratio drink was moderately higher
      than that with the 0.5 ratio (2.9%; 99% confidence interval, +/-2.8%) and 1.25
      ratio (3.1%; +/-2.7%) drinks, with total- and endogenous-CHO oxidation rate,
      abdominal cramps, and drink sweetness qualifying as explanatory mechanisms.
      CONCLUSIONS: Enhanced high-intensity endurance performance with a 0.8 ratio
      fructose-maltodextrin-glucose drink is characterized by higher exogenous-CHO
      oxidation efficiency and reduced endogenous-CHO oxidation. The gut-hepatic or
      other physiological site responsible requires further research.

PMID- 23949098
TI  - Resonance energy transfer in self-organized organic/inorganic dendrite
      structures.
AB  - Hybrid materials formed by semiconductor quantum dots and J-aggregates of cyanine
      dyes provide a unique combination of enhanced absorption in inorganic
      constituents with large oscillator strength and extremely narrow exciton bands of
      the organic component. The optical properties of dendrite structures with fractal
      dimension 1.7-1.8, formed from J-aggregates integrated with CdTe quantum dots
      (QDs), have been investigated by photoluminescence spectroscopy and fluorescence
      lifetime imaging microscopy. Our results demonstrate that (i) J-aggregates are
      coupled to QDs by Forster-type resonant energy transfer and (ii) there are energy
      fluxes from the periphery to the centre of the structure, where the QD density is
      higher than in the periphery of the dendrite. Such an anisotropic energy
      transport can be only observed when dendrites are formed from QDs integrated with
      J-aggregates. These QD/J-aggregate hybrid systems can have applications in light
      harvesting systems and optical sensors with extended absorption spectra. 

PMID- 23949099
TI  - Prejudices and elderly patients' personality -- the problem of quality of care
      and quality of life in geriatric medicine.
AB  - BACKGROUND: The article discusses the position of elderly patients in medical
      intervention context. The phenomenon of greying population has changed the
      attitude towards the old but common observations prove that quality of geriatric
      care is still unsatisfactory. In order to improve specialists' understanding of
      ageing, the comparative study on personality among people at different age was
      designed. The results are discussed in relation to the elderly patient-centred
      paradigm and in order to counterbalance still present ageist practices. MATERIAL
      AND METHODS: The research involved 164 persons in the early and late adulthood
      stage ages. Among the old there were the young old (aged 65-74) and the older old
      (aged 75+). All participants were asked to fill the NEO-FFI. RESULTS: The results
      prove age-related differences in personality. In late adulthood in comparison to
      early adulthood there is the decline in openness to experiences. Two traits:
      agreeableness and conscientiousness increase significantly. Age did not
      differentiate significantly the level of neuroticism and of extraversion. The
      results of cluster analyses show the further differences in taxonomies of
      personality traits at different period of life. CONCLUSIONS: The results
      challenge the stereotypes that present older people as neurotic, and aggressive.
      The age did not differentiate significantly the level of neuroticism and of
      extraversion. In general, the obtained results prove that the ageist assumption
      that the geriatric patients are troublesome is not arguable. This article builds
      support for effective change in geriatric professional practices and improvement
      in the elderly patients' quality of life.

PMID- 23949100
TI  - Problem coping skills, psychosocial adversities and mental health problems in
      children and adolescents as predictors of criminal outcomes in young adulthood.
AB  - The purpose of this study was to test child and adolescent psychosocial and
      psychopathological risk factors as predictors of adult criminal outcomes in a
      Swiss community sample. In particular, the role of active and avoidant problem
      coping in youths was analysed. Prevalence rates of young adult crime convictions
      based on register data were calculated. Univariate and multivariate logistic
      regressions were used to analyse the prediction of adult criminal convictions 15
      years after assessment in a large Swiss community sample of children and
      adolescents (n = 1,086). Risk factors assessed in childhood and adolescence
      included socio-economic status (SES), migration background, perceived parental
      behaviour, familial and other social stressors, coping styles, externalizing and
      internalizing problems and drug abuse including problematic alcohol consumption.
      The rate of any young adult conviction was 10.1 %. Besides externalizing problems
      and problematic alcohol consumption, the presence of any criminal conviction in
      young adulthood was predicted by low SES and avoidant coping even after
      controlling for the effects of externalizing problems and problematic alcohol
      use. The other predictors were significant only when externalizing behaviours and
      problematic alcohol use were not controlled. In addition to child and adolescent
      externalizing behaviour problems and substance use, low SES and inadequate
      problem-solving skills, in terms of avoidant coping, are major risk factors of
      young adult criminal outcomes and need to be considered in forensic research and
      criminal prevention programs. 

PMID- 23949101
TI  - Screening for substance use disorders in neurodevelopmental disorders: a clinical
      routine?
AB  - Evidence suggests that substance use disorders (SUD) tend to be underdiagnosed in
      psychiatry. The objective of this study was to investigate whether drug and
      alcohol screening is a clinical routine in the assessment of two prominent
      neurodevelopmental disorders, namely ADHD and autism spectrum disorder (ASD). We
      surveyed drug and alcohol screening routines in 34 general child and adolescent
      (only practice for adolescents, not children, was assessed) and 29 adult
      psychiatric outpatient departments in Stockholm County, Sweden. Structured
      telephone interviews mapping SUD screening procedures were conducted with
      department representatives in charge. Only a minority of child and adolescent
      departments regularly used SUD screening questionnaires (6 %) in ADHD and ASD
      assessment, while this was more common in adult psychiatry (55 %). Urine/blood
      based toxicology tests were always used in 28 % and sometimes or in case of
      clinical suspicion in 38 % of the adult units. Such tests were used sometimes or
      in case of clinical suspicion in 15 % of the child psychiatric departments, but
      never routinely. Findings reveal that screening for SUD in ADHD and ASD is not an
      integral part of routine clinical assessments in psychiatry, although
      increasingly an integral part of many clinical guidelines. Thus, SUD might be
      underdiagnosed in neurodevelopmental disorders, which could be particularly true
      for child and adolescent psychiatry settings. 

PMID- 23949102
TI  - Self-reported emotional and behavioral symptoms, parent-adolescent bonding and
      family functioning in clinically referred adolescent offspring of Croatian PTSD
      war veterans.
AB  - The presence of posttraumatic stress disorder (PTSD) in male war veterans has
      been linked with family dysfunction and psychopathology in their children [1, 2].
      This study aimed to evaluate self-reported emotional and behavioral symptoms,
      parent-adolescent bonding and family functioning in clinically referred
      adolescent offspring of Croatian PTSD war veterans and determine the degree that
      parent-child bonding and family functioning contributed to adolescent behavior
      problems. Internalizing and externalizing behavior problems, parent-child bonding
      and family functioning were assessed in a sample of clinically referred Croatian
      PTSD veterans adolescent offspring (N = 122) and non-PTSD veteran adolescent
      offspring (N = 122) matched for age, sex, educational level, family income,
      parental employment status, ethnicity, and residential area. Youth Self-Report,
      Parental Bonding Instrument, Family Assessment Device were used. Adolescent
      offspring of PTSD veterans reported having significantly more internalizing and
      externalizing problems than non-PTSD veteran offspring, and also more
      difficulties in their family functioning, lower levels of maternal and paternal
      care, and more impaired mother-child and father-child bonding than control
      subjects. Internalizing symptoms were associated with family dysfunction, while
      externalizing symptoms were associated with paternal overcontrol/overprotection,
      and low maternal and paternal care. In conclusion, the increase in internalizing
      and externalizing symptoms as well as family and parental dysfunction among
      clinically referred adolescent offspring of PTSD veterans compared to their non
      PTSD veteran counterparts indicates a need for early detection and interventions
      targeting both adolescent psychopathology and family relationships. 

PMID- 23949103
TI  - Family structure, marital discord and offspring's psychopathology in early
      adulthood: a prospective study.
AB  - With marital breakdown and discord relatively common, we examined whether family
      structure and the quality of marital relationship have a long-term impact on
      offspring's psychopathology in early adulthood. This study aimed to examine the
      association of family structure and marital discord in the family with a wide
      range of offspring's mental health and problem behaviours at 21 years. Data were
      from the Mater-University of Queensland Study of Pregnancy, a population based
      birth cohort study, which commenced in Brisbane, Australia in 1981. Mothers and
      children were followed up at birth, 6 months and 5, 14 and 21 years after the
      initial interview. Marital status and marital quality were assessed at the 14
      year follow-up. Young Adult Self-Report sub-scales of mental health and problem
      behaviours were measured at the 21-year follow-up. Type of family structure and
      the quality of marital relationship (at the 14-year follow-up) predicted
      offspring's psychopathology at 21 years. When a selected group of confounding
      factors were included in the multivariate analyses, children who lived with a
      step-father, un-partnered mother, or in families where parents had conflict in
      marital relationship reported higher symptoms of psychopathology at 21 years. The
      association between marital problems and young adult psychopathology does not
      appear to be confounded by a wide range of confounding variables. Further
      research is needed to explore the mechanism of these associations to develop
      preventive programmes. 

PMID- 23949104
TI  - Radiation exposure before and after the introductionof a dedicated total-body CT
      protocolin multitrauma patients.
AB  - Total-body CT (TBCT) scanning in trauma patients is being increasingly used in
      trauma assessment. One of the major disadvantages of CT scanning is the amount of
      radiation exposure involved. The aim of this study was to assess the number of
      radiological investigations and their associated radiation exposure in
      multitrauma patients before and after the introduction of a total-body CT
      protocol as a primary diagnostic tool. The Trauma Registry was used to identify
      trauma patients admitted to our Level 1 trauma centre in 2008 (pre-TBCT protocol)
      and 2010 (post-TBCT protocol). Consecutive patients with an Injury Severity Score
      of >=16 were included. Patients aged 16 or under, referrals from other hospitals
      and patients with specific low-energy injury mechanisms were excluded. Subsequent
      effective doses were estimated from literature and from dose calculations. Three
      hundred one patients were included, 150 patients pre- and 151 post-introduction
      of the TBCT protocol. Demographics were comparable. In 2008, 20 % of severely
      injured patients underwent total-body CT scan, compared with 46 % of the patients
      in 2010. Trauma room radiation doses for conventional radiographs were
      significantly higher in 2008, while doses for CT scans were significantly lower.
      The total effective dose of trauma room radiological investigations was 16
      milliSieverts (mSv) in 2008 vs. 24 mSv in 2010 (P = 0.223). The overall effective
      dose during the total hospital admission was not significantly different between
      2008 and 2010 (20 vs. 24 mSv, P = 0.509).In conlusion, after the introduction of
      a dedicated TBCT protocol, the TBCT rate was more than doubled. Although this
      increased the CT-induced trauma room radiation dose, the overall radiation dose
      throughout hospital admission was comparable between patients in 2008 and 2010. 

PMID- 23949105
TI  - Musculoskeletal: what is different in children? Riding on his dirt bike--falls:
      foot trapped on ground.

PMID- 23949107
TI  - Identification of molecular recognition of Langmuir-Blodgett monolayers using
      surface-enhanced Raman scattering spectroscopy.
AB  - A facile and effective approach for SERS identification of molecular recognition
      in Langmuir-Blodgett monolayers on smooth substrates was developed by spreading
      Ag nanoparticles on ordered alkyl chains in the monolayers, which acted as a
      spacer layer to separate analytes of interest from direct contact with active
      substrates. 

PMID- 23949106
TI  - The Morel-Lavallee lesion: pathophysiology, clinical presentation, imaging
      features, and treatment options.
AB  - Morel-Lavallee lesions are posttraumatic hemolymphatic collections related to
      shearing injury and disruption of interfascial planes between subcutaneous soft
      tissue and muscle. We review the pathophysiology of Morel-Lavallee lesions,
      clinical presentation, and potential sites of involvement. Magnetic resonance
      imaging (MRI) is the modality of choice for characterization. We present the MRI
      classification and highlight the key imaging features that distinguish the
      different types, focusing on the three most common: seroma, subacute hematoma,
      and chronic organizing hematoma. Potential mimics of Morel-Lavallee lesions, such
      as soft tissue sarcoma and hemorrhagic prepatellar bursitis, are compared and
      contrasted. Treatment options and a management algorithm are also briefly
      discussed.

PMID- 23949108
TI  - The role of adjuvant radiotherapy in atypical meningioma.
AB  - The object of this study was to analyze treatment outcomes and to identify the
      prognostic factors, with a focus on the role of adjuvant radiotherapy (ART),
      predicting disease progression in atypical meningiomas. From 1997 to 2011, 83
      patients with meningioma were included in this study. All patients were
      histologically confirmed as atypical meningioma and were treated with surgical
      resection with or without ART. As primary therapy, 27 patients received surgical
      resection followed by ART, and 56 received no adjuvant therapy. Of 83 evaluable
      patients, 55 (66.3 %) patients underwent complete resection. The median ART dose
      was 61.2 Gy and their median age was 52 years. The 5- and 10-year actuarial
      overall survival rates were 90.2 and 62.0 %, and the 5- and 10-year progression
      free survival (PFS) rates were both 48.0 %, with a median follow-up of 43.0
      months. Addition of ART (p = 0.016) and complete tumor resection (p = 0.002) were
      associated with superior PFS. When stratified to four groups according to
      resection status and ART, the groups of patient with incomplete resection without
      ART showed significantly worse PFS compared to other three groups (p < 0.001). In
      conclusion, surgical resection followed by ART led to lower local tumor
      progression in patients with atypical meningioma defined by the updated 2000/2007
      WHO classification. Our results may contribute to the routine use of ART,
      especially after incomplete resection, until the outcomes of ongoing prospective
      trials are available.

PMID- 23949109
TI  - Rapid and efficient removal of Ni(2+) from aqueous solution by the one-pot
      synthesized EDTA-modified magnetic nanoparticles.
AB  - A facile one-pot process has been proposed to prepare the novel
      ethylenediaminetetraacetic acid (EDTA)-modified magnetite nanoparticles (EDTA
      MNPs). The bared Fe3O4 magnetite nanoparticles and EDTA-MNPs were characterized
      using FTIR spectroscopy, TEM, VSM, and X-ray diffraction. The application of the
      modified magnetite nanoparticles for metal ion uptake was studied using Ni(2+) as
      a model. The adsorption was fast and the equilibrium was established within 5
      min, and the adsorption kinetics of Ni(2+) onto EDTA-MNPs followed the pseudo
      second-order chemisorption mechanism. Maximum adsorption capacity for Ni(2+)
      reached as high as 41.3 mg/g at pH 6. The successive adsorption-desorption
      studies indicated that the EDTA-MNPs kept the adsorption and desorption
      efficiencies constant over ten cycles. Importantly, EDTA-MNPs were able to remove
      nearly 100 % of Ni(2+) from real water.

PMID- 23949110
TI  - Fate of nickel in a lime-stabilized biosolid, a calcareous soil and soil-biosolid
      mixtures.
AB  - Soil contamination with anthropogenic metals resulting from biosolid application
      is widespread around the world. To better predict the environmental fate and
      mobility of contaminants, it is critical to study the capacity of biosolid
      amended soils to retain and release metals. In this paper, nickel adsorption onto
      a calcareous soil, a lime-stabilized biosolid, and soil-biosolid mixtures (30,
      75, and 150 t biosolid/ha) was studied in batch experiments. Sorption experiments
      showed that (1) Ni adsorption was higher onto the biosolid than the calcareous
      soil, and (2) biosolid acted as an adsorbent in the biosolid-soil mixtures by
      increasing Ni retention capacity. The sorption tests were complemented with the
      estimation of Ni adsorption reversibility by successive applications of
      extraction solutions with water, calcium (100 mg/L), and oxalic acid (equivalent
      to 100 mg carbon/L). It has been shown that Ni desorption rates in soil and
      biosolid-amended soils were lower than 30 % whatever the chemical reagent,
      indicating that Ni was strongly adsorbed on the different systems. This
      adsorption/desorption hysteresis effect was particularly significant at the
      highest biosolid concentration (150 t/ha). Finally, an adsorption empirical model
      was used to estimate the maximum permissible biosolid application rate using
      French national guideline. It has been shown that desorption effects should be
      quantitatively considered to estimate relevant biosolid loadings.

PMID- 23949111
TI  - Performance of ANFIS versus MLP-NN dissolved oxygen prediction models in water
      quality monitoring.
AB  - We discuss the accuracy and performance of the adaptive neuro-fuzzy inference
      system (ANFIS) in training and prediction of dissolved oxygen (DO)
      concentrations. The model was used to analyze historical data generated through
      continuous monitoring of water quality parameters at several stations on the
      Johor River to predict DO concentrations. Four water quality parameters were
      selected for ANFIS modeling, including temperature, pH, nitrate (NO3)
      concentration, and ammoniacal nitrogen concentration (NH3-NL). Sensitivity
      analysis was performed to evaluate the effects of the input parameters. The
      inputs with the greatest effect were those related to oxygen content (NO3) or
      oxygen demand (NH3-NL). Temperature was the parameter with the least effect,
      whereas pH provided the lowest contribution to the proposed model. To evaluate
      the performance of the model, three statistical indices were used: the
      coefficient of determination (R (2)), the mean absolute prediction error, and the
      correlation coefficient. The performance of the ANFIS model was compared with an
      artificial neural network model. The ANFIS model was capable of providing greater
      accuracy, particularly in the case of extreme events. 

PMID- 23949112
TI  - Geochemical modeling of arsenic release from a deep natural solid matrix under
      alternated redox conditions.
AB  - Dissolved arsenic (As) concentrations detected in groundwater bodies of the
      Emilia-Romagna Region (Italy) exhibit values which are above the regulation limit
      and could be related to the natural composition of the host porous matrix. To
      support this hypothesis, we present the results of a geochemical modeling study
      reproducing the main trends of the dynamics of As, Fe, and Mn concentrations as
      well as redox potential and pH observed during batch tests performed under
      alternating redox conditions. The tests were performed on a natural matrix
      extracted from a deep aquifer located in the Emilia-Romagna Region (Italy). The
      solid phases implemented in the model were selected from the results of selective
      sequential extractions performed on the tested matrix. The calibrated model
      showed that large As concentrations have to be expected in the solution for low
      crystallinity phases subject to dissolution. The role of Mn oxides on As
      concentration dynamics appears significant in strongly reducing environments,
      particularly for large water-solid matrix interaction times. Modeled data
      evidenced that As is released firstly from the outer surface of Fe oxihydroxides
      minerals exhibiting large concentrations in water when persistent reducing
      conditions trigger the dissolution of the crystalline structure of the binding
      minerals. The presence of organic matter was found to strongly affect pH and
      redox conditions, thus influencing As mobility. 

PMID- 23949113
TI  - Effects of sodium arsenate exposure on liver fatty acid profiles and oxidative
      stress in rats.
AB  - The present study aimed to evaluate the effect of arsenic on liver fatty acids
      (FA) composition, hepatotoxicity and oxidative status markers in rats. Male rats
      were randomly devised to six groups (n=10 per group) and exposed to sodium
      arsenate at a dose of 1 and 10 mg/l for 45 and 90 days. Arsenate exposure is
      associated with significant changes in the FA composition in liver. A significant
      increase of saturated fatty acids (SFA) in all treated groups (p<0.01) and trans
      unsaturated fatty acids (trans UFA) in rats exposed both for short term for 10
      mg/l (p<0.05) and long term for 1 and 10 mg/l (p<0.001) was observed. However,
      the cis UFA were significantly decreased in these groups (p<0.05). A markedly
      increase of indicator in cell membrane viscosity expressed as SFA/UFA was
      reported in the treated groups (p<0.001). A significant increase in the level of
      malondialdehyde by 38.3 % after 90 days of exposure at 10 mg/l was observed.
      Compared to control rats, significant liver damage was observed at 10 mg/l of
      arsenate by increasing plasma marker enzymes after 90 days. It is through the
      histological investigations in hepatic tissues of exposed rats that these damage
      effects of arsenate were confirmed. The antioxidant perturbations were observed
      to be more important at groups treated by the high dose (p<0.05). An increase in
      the level of protein carbonyls was observed in all treated groups (p<0.05). The
      present study provides evidence for a direct effect of arsenite on FA composition
      disturbance causing an increase of SFA and TFAs isomers, liver dysfunction and
      oxidative stress. Therefore, arsenate can lead to hepatic damage and propensity
      towards liver cancer.

PMID- 23949114
TI  - Malnutrition in an elderly population without cognitive impairment living in
      nursing homes in Spain: study of prevalence using the Mini Nutritional Assessment
      test.
AB  - BACKGROUND: The prevalence of malnutrition in institutionalized elderly people is
      generally high. A good nutritional status is related to a decrease in mortality
      and costs of morbidity treatments. Therefore, it is essential to know the
      nutritional status in order to establish action policies. However, there are not
      enough studies about malnutrition in institutionalized elderly in Spain.
      OBJECTIVES: The objectives of this survey were to assess the prevalence of
      malnutrition and risk of malnutrition in elderly people living in nursing homes
      in the province of Albacete (Spain) using the Mini Nutritional Assessment
      (MNA(r)) test, to analyze their distribution according to age, gender and
      different nursing home features, and to identify the MNA items that best predict
      the MNA total score. METHODS: A cross-sectional study was conducted with data
      collected from 895 elders living in 34 nursing homes all over the province of
      Albacete, including facilities located in the main city, towns and villages.
      Prevalence of malnutrition and risk of malnutrition were assessed using the MNA
      full form test. Groups of malnutrition were compared by using mean MNA scores.
      Stepwise linear regression analyses were used to identify the items in the MNA
      which best predicted the MNA total scores. RESULTS: According to the MNA, the
      prevalence of malnutrition among elderly people staying in Albacete province
      nursing homes was 2.8%, and the prevalence of being at risk of malnutrition was
      37.3%. MNA total score was significantly higher in men (24.3 +/- 2.9) than in
      women (23.7 +/- 3.3) and significantly higher in residents living in nursing
      homes located in towns and villages (24.2 +/- 2.8) than in those who were living
      in institutions placed in the main city (23.7 +/- 3.4). The MNA score was found
      to decrease with increasing age, except for individuals aged 90 years or older.
      CONCLUSIONS: The prevalence of malnutrition and risk of malnutrition was 40.1%.
      Female gender and living in institutions located in the main city were identified
      as malnutrition risk factors. In general, an increase in malnutrition with age
      was detected, except for people in the last years of their lives. The MNA
      questions that best predicted the nutritional status were the ones relating to
      the anthropometrical and self-assessments.

PMID- 23949115
TI  - Selective anion exchange with nanogated isoreticular positive metal-organic
      frameworks.
AB  - Crystalline porous materials, especially inorganic porous solids such as
      zeolites, usually have negative frameworks with extra-framework mobile cations
      and are widely used for cation exchange. It is highly desirable to develop new
      materials with positive frameworks for selective anion exchange and separation or
      storage and delivery. Recent advances in metal-organic framework synthesis have
      created new opportunities in this direction. Here we report the synthesis of a
      series of positive indium metal-organic frameworks and their utilization as a
      platform for the anion exchange-based separation process. This process is capable
      of size- or charge-selective ion-exchange of organic dyes and may form the basis
      for size-selective ion chromatography. Ion-exchange dynamics of a series of
      organic dyes and their selective encapsulation and release are also studied,
      highlighting the advantages of metal-organic framework compositions for designing
      host materials tailored for applications in anion separation and purification. 

PMID- 23949116
TI  - Pulpal involvement-roots-sepsis index: a new method for describing the clinical
      consequences of untreated dental caries.
AB  - OBJECTIVES: To describe a modification of the index of clinical consequences of
      untreated dental caries [pulpal involvement, ulceration, fistula and abscess
      (PUFA/pufa) index] to pulpal involvement-roots-sepsis (PRS/prs) and to compare
      the two indices using the example of caries in primary molar teeth in children
      aged 6-8 years. SUBJECTS AND METHODS: The study sample included 542 children aged
      6-8 years, from five randomly selected schools in the Bialystok District, Poland.
      The occurrence of clinical consequences of untreated caries in deciduous molars
      using the pufa and prs indices was evaluated. Data were analysed to express the
      prevalence, the experience and the distribution of particular pufa and prs codes
      in the sample population. The differences in layout of the pufa and prs
      components were expressed. RESULTS: The response rate was 77.6%. The prevalence
      of the clinical consequences of untreated caries was 40.77%, mean pufa and prs
      were the same (0.85 +/- 1.33). According to the pufa index, the following mean
      values were obtained: p = 0.79, u = 0.01, f = 0.04 and a = 0.01. For the prs
      index, the mean values were as follows: p = 0.45, r = 0.35 and s = 0.05.
      CONCLUSION: The proposed prs index was a useful epidemiological instrument for
      the evaluation of the clinical consequences of untreated caries in the surveyed
      population. The PRS instrument could be a good alternative to the PUFA index.

PMID- 23949117
TI  - Synergistic cooperation of PDI family members in peroxiredoxin 4-driven oxidative
      protein folding.
AB  - The mammalian endoplasmic reticulum (ER) harbors disulfide bond-generating
      enzymes, including Ero1alpha and peroxiredoxin 4 (Prx4), and nearly 20 members of
      the protein disulfide isomerase family (PDIs), which together constitute a
      suitable environment for oxidative protein folding. Here, we clarified the Prx4
      preferential recognition of two PDI family proteins, P5 and ERp46, and the mode
      of interaction between Prx4 and P5 thioredoxin domain. Detailed analyses of
      oxidative folding catalyzed by the reconstituted Prx4-PDIs pathways demonstrated
      that, while P5 and ERp46 are dedicated to rapid, but promiscuous, disulfide
      introduction, PDI is an efficient proofreader of non-native disulfides.
      Remarkably, the Prx4-dependent formation of native disulfide bonds was
      accelerated when PDI was combined with ERp46 or P5, suggesting that PDIs work
      synergistically to increase the rate and fidelity of oxidative protein folding.
      Thus, the mammalian ER seems to contain highly systematized oxidative networks
      for the efficient production of large quantities of secretory proteins. 

PMID- 23949120
TI  - Oxygen reduction reaction catalyzed with titanyl phthalocyanines in nonaqueous
      and aqueous media.
AB  - Electrochemical and in situ spectroelectrochemical behaviors and electrocatalytic
      reduction of molecular oxygen with titanyl phthalocyanines (TiPc) bearing 3,4
      (methylenedioxy)-phenoxy substituents were performed in aprotic solvents. Multi
      electrons and metal-based and ring-based redox processes of TiPcs indicate their
      possible electrocatalytic activity toward many target species. Different numbers
      and positions of the substituents of the complexes affect the peaks' character
      and assignment of the processes. The presence of O2 in the electrolyte system
      influences the electrochemical and spectral responses of TiPcs. Electrochemical
      and in situ spectroelectrochemical analysis indicates interaction of molecular
      oxygen with TiPcs and these interaction mechanisms depend on both the substituent
      environments of the complexes and the electrolyte system. Langmuir-Blodgett films
      of the complexes also catalyze molecular oxygen in aqueous media, which is a
      desired property for their practical application. 

PMID- 23949118
TI  - Tempol ameliorates cardiac fibrosis in streptozotocin-induced diabetic rats: role
      of oxidative stress in diabetic cardiomyopathy.
AB  - Long-standing diabetes is associated with increased oxidative stress and cardiac
      fibrosis. This, in turn, contributes to the progression of cardiomyopathy. The
      present study was sought to investigate whether the free radical scavenger, 4
      hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol) can protect against diabetic
      cardiomyopathy and to explore the specific underlying mechanism(s) in this
      setting. Diabetes was induced in rats by a single intraperitoneal injection dose
      of streptozotocin (50 mg/kg). These animals were treated with tempol (18 mg kg(
      1) day(-1), orally) for 8 weeks. Our results showed significant increases in
      collagen IV and fibronectin protein levels and a marked decrease in matrix
      metalloproteinase-2 (MMP-2) activity measured by gelatin-gel zymography alongside
      elevated cardiac transforming growth factor (TGF)-beta level determined using
      ELISA or immunohistochemistry in cardiac tissues of diabetic rats compared with
      control. This was accompanied by an increased in the oxidative stress as
      evidenced by increased reactive oxygen species (ROS) production and decreased
      antioxidant enzyme capacity along with elevated lactate dehydrogenase (LDH) and
      creatine kinase (CK-MB) serum levels as compared with the control. Tempol
      treatment significantly corrected the changes in the cardiac extracellular
      matrix, TGF-beta, ROS or serum LDH, CK-MB levels, and normalized MMP-2 activity
      along with preservation of cardiac tissues integrity of diabetic rats against
      damaging responses. Moreover, tempol normalized the elevated systolic blood
      pressure and improved some cardiac functions in diabetic rats. Collectively, our
      data suggest a potential protective role of tempol against diabetes-associated
      cardiac fibrosis in rats via reducing oxidative stress and extracellular matrix
      remodeling.

PMID- 23949119
TI  - Type of hematological malignancy is crucial for the return to work prognosis: a
      register-based cohort study.
AB  - PURPOSE: The aims of this study were to determine the proportion of return to
      work (RTW) among sick-listed patients diagnosed with one of eight subtypes of
      hematological malignancies; to evaluate the influence of type of hematological
      malignancy, comorbidity, use of anxiolytics and antidepressants, socioeconomic
      and demographic factors on RTW; and to investigate if these associations differ
      between genders. METHODS: We combined data from national registers on all Danish
      patients diagnosed with hematological malignancies between 2000 and 2007. A total
      of 1,741 patients on long-term sick leave were followed until RTW, emigration,
      permanent withdrawal from the labor market, death, or February 2012, whichever
      came first. RESULTS: A total of 1,140 (65 %) patients returned to work. A strong
      association was found between type of diagnosis and RTW (p < 0.001), and the
      proportion of RTW was lowest for patients with multiple myeloma or acute leukemia
      compared to patients with Hodgkin lymphoma, diffuse large B-cell lymphoma,
      follicular lymphoma, chronic myeloid leukemia, and chronic lymphoid leukemia. Use
      of antidepressants or anxiolytics after diagnosis, gender, age, and educational
      level were also associated with RTW. Surprisingly, comorbidity was not associated
      with RTW (p = 0.94); gender only modified the association between age and RTW.
      CONCLUSION: Two thirds of patients with hematological malignancies on sick leave
      RTW. A number of factors seem to lead to a poor prognosis, the hematological
      diagnosis being the most important, and these should be taken into account when
      performing studies on work outcome for patients with hematological malignancies.
      IMPLICATIONS FOR CANCER SURVIVORS: Knowledge in this area should assist in
      identification of hematological cancer patients at risk of not returning to work
      so that early targeted rehabilitation interventions can be initiated.

PMID- 23949121
TI  - Ketotifen-induced nocturnal bruxism.
AB  - Nocturnal bruxism is a common oromandibular movement disorder highly prevalent in
      children, but its pathophysiological mechanism has not been fully explained.
      Iatrogenic sleep bruxism has been described following treatment with several
      psychotropic medications. However, no case of antihistamine-induced bruxism has
      been reported to date. Herein, we describe a 4-year-old child who experienced
      nocturnal bruxism during treatment for bronchospasm and rhinitis with the
      antihistamine ketotifen. Drug rechallenge was also performed. CONCLUSION: The
      present case adds useful information to our knowledge of bruxism. Complex and
      poorly understood interactions between multiple central nervous system
      neurotransmitters, such as histamine, serotonin, and dopamine, are involved.

PMID- 23949122
TI  - Reply to correspondence letter: is pro-adrenomedullin more useful marker in
      hospitalized infants with sepsis?

PMID- 23949123
TI  - Dr. Jerome P. Webster's surgical practice in China.

PMID- 23949124
TI  - Application of cicatricial contracture release principles in muscular torticollis
      treatment.
AB  - BACKGROUND: Numerous surgical approaches for muscular torticollis are not
      effective enough to completely release the contracture and prevent further
      development of craniofacial asymmetry. Cosmetically unacceptable scars on the
      neck and compulsory functional exercises after surgery were also common problems.
      We applied the therapeutic principle of scar contracture to the surgical
      treatment of muscular torticollis. Surgical incision determination and the
      postoperative protocol were considerably improved. Satisfactory results were
      obtained. METHOD: According to the therapeutic principle of scar contracture,
      complete release of the contracted muscles and peripheral streak fascia and
      release or partial resection of peripheral normal tissues such as the scalenus
      anterior, anterior trapezius border, platysma, and partial carotid sheath are
      required to release all the affected contracted and tightened tissues. We chose
      to incise underneath the affected side of the clavicular border. We obtained a
      tension-free closure of the incision through an advanced skin flap of the
      inferior incision sutured on the clavicular fascia. Maximum head and neck stretch
      to the unaffected side of the shoulder when the patient lied down gave the
      affected side lateral decubitus position after surgery. RESULTS: Satisfactory
      results were obtained and no complications were identified for all of the 104
      patients. The development of craniofacial asymmetry and progressive deformities
      was prevented. The incision scar appeared linear in the pit above or below the
      clavicle border and was relatively inconspicuous. CONCLUSION: The application of
      the therapeutic principle of scar contracture to the surgical treatment of
      muscular torticollis was successful.

PMID- 23949125
TI  - Effect of the depressor septi nasi muscle on nasal lengthening over time.

PMID- 23949126
TI  - Does reduction mammaplasty revert skeletal disturbances in the vertebral column
      of patients with macromastia? A preliminary study.
AB  - BACKGROUND: Enlarged breasts are associated with many physical and psychological
      symptoms. It is important to use objective criteria in documenting physical
      changes of a patient's body due to enlarged breasts and the benefits of surgery.
      This preliminary study aimed to determine whether the reduction mammaplasty
      procedure changes the angles of cervical lordosis, thoracic kyphosis, and lumbar
      lordosis. METHODS: The study population consisted of 22 patients who underwent
      breast reduction surgery. All the patients had lateral cervicothoracolumbar
      radiographs taken preoperatively and at least 2 months postoperatively. Cervical
      lordosis, thoracic kyphosis, and lumbar lordosis angles, as well as sagittal
      balance, were examined. The body mass index (BMI), breast tissue volume, and
      excised tissue amount of each patient were recorded. RESULTS: All the patients
      had increased cervical lordosis and thoracic kyphosis angles preoperatively, and
      the angles were significantly decreased postoperatively. Of the 22 patients, 7
      had decreased and 8 had increased lumbar lordosis angles. All the lordosis angles
      showed significant improvement at the last examination. Seven patients had
      disturbed sagittal balance preoperatively, and all had normal sagittal balance
      postoperatively. Preoperative total breast tissue volume was positively
      correlated with the differences in cervical lordosis angles, BMI, preoperative
      cervical lordosis angles, and cervical lordosis angles. CONCLUSION: Hypertrophic
      breasts are not only a cosmetic but also a functional problem complicated by
      pathologic conditions in the vertebral column such as increased cervical
      lordosis, thoracic kyphosis, and increased or decreased lumbar lordosis. Breast
      reduction may improve these pathologic angles. Reducing the nonphysiologic weight
      of enlarged breasts located anterior to the main axis of the body may correct
      pathologic angulation and disturbed sagittal balance of the vertebral column.
      LEVEL OF EVIDENCE IV: 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- 23949127
TI  - Superficial leiomyosarcoma of the glans: report of a case and literature review.
AB  - Primary leiomyosarcomas of the penis are rare. Clinically and pathologically,
      these tumors fall into two groups: superficial and deep. Superficial lesions
      usually are low grade and show a limited tendency toward distant metastasis. In
      contrast, deep-seated tumors usually show a more aggressive behavior associated
      with a poor prognosis. A 62-year-old man with a superficial leiomyosarcoma of the
      glans penis is reported.

PMID- 23949128
TI  - Adenovirus-mediated expression of keratinocyte growth factor promotes secondary
      flap necrotic wound healing in an extended animal model.
AB  - BACKGROUND: No effective treatments have been found for flap necrosis. Animal
      models that focus on the initial flap viability are inappropriate for necrotic
      wound studies. Keratinocyte growth factor (KGF) promotes keratinocyte
      proliferation with stronger activity and fewer complications and thus may be
      useful for necrotic flap wound healing. METHODS: Rats with modified flap necrosis
      were randomly divided into four groups. An adenoviral vector expressing KGF was
      injected subdermally in the back of the animals after necrosis began. The
      expression and effect of KGF was assessed by real-time polymerase chain reaction,
      enzyme-linked immunoassay, and transwell, and wound healing was monitored.
      RESULTS: The plasmid and adenovirus were able to express KGF and stimulate
      epithelial cell growth (p = 0.029). Histology showed that the necrosis healed
      fastest in the KGF administration group than in the control groups (p < 0.01).
      The adenovirus-mediated KGF (Ad-KGF) group had the thickest epithelium on days 15
      (p = 0.044) and 25 (p = 0.014). The KGF level in the blood serum soared 10 and 15
      days postoperatively (p < 0.01) but returned to baseline by day 25 (p = 0.561).
      The KGF mRNA levels in vivo increased dramatically in the Ad-KGF group (p =
      0.037). CONCLUSIONS: The extended flap model is applicable in necrotic wound
      study. Keratinocyte growth factor can promote secondary necrotic flap wound
      healing, and administration of KGF can be achieved by an adenoviral vector.

PMID- 23949129
TI  - A rare case of lymphangioma in the gluteal region: surgical treatment combined
      with sclerotherapy and laser therapy.
AB  - BACKGROUND: Lymphangioma, a rare benign malformation of lymphatic channels, is
      among the surgically treatable diseases of the lymphatic vessels. However, damage
      to surrounding structures together with incomplete resection due to adjacent
      organ infiltration and a high recurrence rate have encouraged the search for
      alternative treatments. This study aimed to identify the best therapeutic
      management for this difficult-to-treat disease. METHODS: This report describes a
      case of congenital lymphangioma in the gluteal region in a young woman. First,
      sclerotherapy of the lymphangioma was performed and then surgical excision of
      residual lesions. Finally, as a third therapeutic step, the patient also was
      subjected to a cycle of laser therapy with the aim of further improving the
      appearance of the gluteal region. Pulsed dye laser was used to remove cutaneous
      dyschromias, and an erbium:yttrium-aluminum-garnet laser was used to remove
      surface irregularities and obtain better skin smoothness. The outcome assessments
      included standardized photography, the physician's global assessment, the
      patient's satisfaction scores, and magnetic resonance imaging of the gluteal
      region. RESULTS: All the lesions of lymphangioma were removed. After the last
      laser treatment, the skin of the entire treated region was eutrophic and uniform
      in color, and it appeared to be smooth and soft when palpated. The patient was
      satisfied with the clinical and aesthetic results achieved. CONCLUSIONS: The
      combination of sclerotherapy with surgery can be a good solution for the
      treatment of lymphangioma. The authors also propose laser therapy as an
      additional therapeutic approach that may follow surgery or sclerotherapy with the
      aim of improving the skin trophism and the appearance of the affected region.

PMID- 23949130
TI  - Hemostatic net in rhytidoplasty: an efficient and safe method for preventing
      hematoma in 405 consecutive patients.
AB  - BACKGROUND: Hematoma is the most common postoperative complication of
      rhytidoplasty, resulting in higher morbidity and longer recovery. Quilting suture
      for closure of the undermined area in abdominoplasty avoids the occurrence of
      seroma. Based on this principle and with the objective of reducing the number of
      patients with hematomas in rhytidoplasty, a similar surgical tactic was developed
      in which a hemostatic net is created with a running transfixing suture of 5-0
      nylon encompassing the skin and the superficial musculoaponeurotic system
      platysma. METHODS: The study enrolled 525 consecutive patients who underwent
      rhytidoplasty between July 2009 and February 2013. The first 120 patients (group
      A) were evaluated retrospectively and considered control subjects. The remaining
      405 patients (group B) had application of the described tactic, with data
      collected prospectively. The occurrence of hematoma, ischemia, and necrosis was
      observed during the first 72 h after surgery. RESULTS: Control group A included
      17 patients with hematoma (14.2 %) during the first 72 h, whereas no patient in
      group B experienced such a complication (p < 0.001). The surgical tactic did not
      significantly increase the occurrence of ischemia. This complication was
      experienced by 11 patients in group A (9.2 %) and 26 patients in group B (6.4 %)
      (p = 0.408). The tactic also did not change the incidence of necrosis, which was
      present in three group A patients (2.5 %) and six group B patients (1.5 %) (p =
      0.723). CONCLUSION: The hemostatic net is an efficient and safe method for
      preventing early hematomas in rhytidoplasties. 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- 23949131
TI  - The effect of zinc oxide nanoparticles on mouse spermatogenesis.
AB  - OBJECTIVE: To evaluate the effects of zinc oxide nanoparticles on mouse
      spermatogenesis. METHODS: Thirty two adult male NMRI mice were used. Experimental
      Groups (ZNP-1-ZNP-3) received one of the following treatments daily for 35 days:
      5, 50 and 300 mg/kg zinc oxide nanoparticles respectively. Control group received
      only distilled water. Epididymal sperm parameters, testicular histopathology,
      morphometric analysis and spermatogenesis assessments were performed for
      evaluation of the zinc oxide nanoparticles effects on testis. RESULTS: Epididymal
      sperm parameters including sperm number, motility and percentage of abnormality
      were significantly changed in 50 and 300 mg/kg zinc oxide nanoparticles treated
      mice (p < 0.01). Histopathological criteria such as epithelial vacuolization,
      sloughing of germ and detachment were significantly increased in 50 and 300 mg/kg
      zinc oxide nanoparticles treated mice (p < 0.001). 300 mg/kg zinc oxide
      nanoparticles induced formation of multinucleated giant cells in the germinal
      epithelium. 50 and 300 mg/kg zinc oxide nanoparticles also caused a significant
      decrease in seminiferous tubule diameter, seminiferous epithelium height and
      maturation arrest (p < 0.001). CONCLUSION: Zinc oxide nanoparticles act as
      testicular toxicant and further studies are needed to establish its mechanism of
      action upon spermatogenesis.

PMID- 23949132
TI  - Illuminated Ando plombe for optimal positioning in highly myopic eyes with
      vitreoretinal diseases secondary to posterior staphyloma.

PMID- 23949133
TI  - [Knee laxity in anterior cruciate ligament reconstruction. The influence of graft
      rotation using interference screw fixation].
AB  - BACKGROUND: The use of interference screws for femoral graft fixation in anterior
      cruciate ligament (ACL) reconstruction with hamstring grafts can result in
      rotation of the graft around the screw leading to changes in the final position
      of the graft within the bone tunnel. MATERIAL AND METHODS: In a prospective study
      107 patients (54 right and 53 left knees) underwent ACL reconstruction with a
      hamstring tendon autograft. Femoral fixation of the graft was performed with a
      standard right-thread screw in all cases. Patients were assessed at 6 months
      postoperatively with the international knee documentation committee (IKDC)
      standard evaluation including instrumented laxity measurements and the results
      were compared between right and left knees. RESULTS: A significantly higher
      postoperative anterior laxity was observed in left knees with a negative Lachman
      test in only 64 % of the cases compared with 87 % in the group of right knees.
      Accordingly, instrumented laxity measurements of the reconstructed knee compared
      with the contralateral knee revealed significant differences between left and
      right knees (left knees 1.8+/-1.2 mm and right knees 1.0+/-1.4 mm) CONCLUSIONS:
      This study demonstrates the importance of femoral graft positioning and its
      sensitivity to multiple influencing factors. The use of standard right-thread
      interference screws for femoral graft fixation in the mirrored situation of right
      and left knees may produce a systematic error in ACL reconstruction. Due to a
      possible rotation of the graft around the screw, the final position of the
      transplant may vary thus leading to significant changes in anterior translation
      of the operated knee.

PMID- 23949134
TI  - [Non-dislocated osteoporotic insufficiency fracture of the medial femoral neck.
      SPECT/CT makes the diagnostic difference].
AB  - Osteoporotic fragility fractures of the femoral neck are the most common type of
      fractures in the elderly and are associated with a high mortality. Most
      frequently these fractures are due to falls but spontaneous onset has also been
      described. In these patients the insufficient quantity and quality of the
      osteoporotic bone finally leads to the development of a fragility or
      insufficiency fracture. In some cases of nondisplaced insufficiency fractures the
      diagnosis cannot be established by conventional radiographs alone and magnetic
      resonance imaging (MRI), single proton emission computed tomography (SPECT) or
      SPECT/CT are considered as diagnostic adjuncts. We report the case of an 83-year
      old patient who had complained of ongoing weight-bearing pelvic pain for over 6
      months. There was no history of trauma. The clinical conventional radiographs as
      well as CT could not elucidate the cause of the problems. To differentiate
      between lumbal and hip pain a SPECT/CT was performed and the diagnosis of a
      medial femoral neck insufficiency fracture was established. In the delayed phase
      a band-like increased tracer uptake within the medial femoral neck was observed.
      The SPECT/CT procedure is a promising diagnostic alternative for geriatric
      patients and can be particularly recommended in cases of persistent unclear
      pelvic or lumbar spine pain in the elderly.

PMID- 23949135
TI  - [Simultaneous bilateral humeral head disclocation and acetabular fracture. A rare
      manifestation after hypoglycemia-induced seizures].
AB  - Seizures can cause severe musculoskeletal injuries and posterior shoulder
      dislocation is a typical result of a seizure. Bilateral posterior shoulder
      dislocation is rare and acetabular fractures caused by a seizure are also a
      rarity. We present the case of a 48-year-old man with simultaneous bilateral
      posterior shoulder fracture dislocations and bilateral acetabular fractures as a
      result of hypoglycemia-induced seizures. 

PMID- 23949136
TI  - L-Arabinose degradation pathway in the haloarchaeon Haloferax volcanii involves a
      novel type of L-arabinose dehydrogenase.
AB  - The pathway of L-arabinose degradation was studied in the haloarchaeon Haloferax
      volcanii. It is shown that L-arabinose is oxidatively degraded to alpha
      ketoglutarate. During growth on L-arabinose, L-arabinose dehydrogenase (L-AraDH)
      was induced. The enzyme was purified as a 130 kDa homotetrameric protein
      catalyzing the oxidation of L-arabinose with both NADP(+) and NAD(+). The gene
      encoding L-AraDH was identified as HVO_B0032 and recombinant L-AraDH showed
      similar properties as the native enzyme. The L-AraDH deletion mutant did not grow
      on L-arabinose, but grew unaffected on glucose and D-xylose, indicating a
      specific involvement in L-arabinose degradation. Phylogenetic analyses attribute
      the first archaeal L-AraDH to the extended short-chain dehydrogenase/reductase
      (SDRe) family, where it is part of a novel cluster and thus differs from known
      archaeal and bacterial pentose dehydrogenases. Further, cell extracts of H.
      volcanii catalyzed the NADP(+)-dependent conversion of L-arabinoate to alpha
      ketoglutarate. The genes involved in that conversion were identified by analyses
      of transcripts and deletion mutants as HVO_B0038A, HVO_B0027 and HVO_B0039
      recently reported to be involved in D-xylonate conversion to alpha-ketoglutarate
      in H. volcanii (Johnsen et al. 2009). 

PMID- 23949137
TI  - Thermophilic and halophilic beta-agarase from a halophilic archaeon Halococcus
      sp. 197A.
AB  - An agar-degrading archaeon Halococcus sp. 197A was isolated from a solar salt
      sample. The agarase was purified by hydrophobic column chromatography using a
      column of TOYOPEARL Phenyl-650 M. The molecular mass of the purified enzyme,
      designated as Aga-HC, was ~55 kDa on both SDS-PAGE and gel-filtration
      chromatography. Aga-HC released degradation products in the order of
      neoagarohexose, neoagarotetraose and small quantity of neoagarobiose, indicating
      that Aga-HC was a beta-type agarase. Aga-HC showed a salt requirement for both
      stability and activity, being active from 0.3 M NaCl, with maximal activity at
      3.5 M NaCl. KCl supported similar activities as NaCl up to 3.5 M, and LiCl up to
      2.5 M. These monovalent salts could not be substituted by 3.5 M divalent cations,
      CaCl2 or MgCl2. The optimal pH was 6.0. Aga-HC was thermophilic, with optimum
      temperature of 70  degrees C. Aga-HC retained approximately 90 % of the initial
      activity after incubation for 1 hour at 65-80  degrees C, and retained 50 %
      activity after 1 hour at 95  degrees C. In the presence of additional 10 mM
      CaCl2, approximately 17 % remaining activity was detected after 30 min at 100 
      degrees C. This is the first report on agarase purified from Archaea. 

PMID- 23949138
TI  - Cardiac aneurysm: a nature's way of correction.
AB  - Cardiac aneurysm occurring in ventricles is usually a complication of acute
      transmural myocardial infarction. The development of cardiac aneurysm represents
      a process of continued thinning and fibrosis of the necrotic tissue of the
      ventricular wall. Survival of the person without any complication depends on the
      development of the solid fibrous scar, which seals the aneurysmal cavity.We
      present an incidental case wherein a person survived with a ventricular aneurysm
      that sealed itself by natural means due to the development of a thrombus and
      fibrous tissue offering a natural protection. The person died because of head
      injury in a road traffic accident in this particular case. 

PMID- 23949139
TI  - Sudden death due to Eagle syndrome: a case report.
AB  - Eagle syndrome represents symptoms manifested by compression of regional
      structures by elongation of the styloid process or ossification of the stylohyoid
      membrane. Various theories have been put forward toward the development of Eagle
      syndrome. Depending on the underlying pathogenetic mechanism and the anatomical
      structures compressed or irritated by the elongated styloid process, symptoms
      vary greatly, ranging from cervicofacial pain to cerebral ischemia. Because the
      symptoms are variable and nonspecific, patients land up in different clinics for
      treatment. In the present case, the victim had previous episode of
      unconsciousness along with frequent headache for which she visited various
      clinics on numerous occasions. The elongated styloid process was appreciated
      during the postmortem examination, and the diagnosis of sudden death due to
      mechanical irritation of the carotid sinus by elongated styloid process was made
      as the sign of acute cardiovascular failure was present and upon exclusion of
      other causes of death. 

PMID- 23949140
TI  - The effectiveness and limitations of triphenyltetrazolium chloride to detect
      acute myocardial infarction at forensic autopsy.
AB  - Triphenyltetrazolium chloride (TTC) is one of the most conventional stains to
      detect infarcted area of the heart in animal experiments. However, its
      availability and limitations have not been thoroughly discussed in the forensic
      field. Here, authors stained human hearts with TTC soon after the harvest.
      Photographs of the samples were analyzed using image analysis software, which
      evaluated the occupying ratio of the stained area on the surface of each slice.
      The results showed that the stainability of TTC declines with the length of the
      postmortem interval (PMI). Specimens reacted well to TTC within 1.5 days after
      death and then decreased the stainability logarithmically with PMI (y = - 0.294
      In (x) + 1.0441; x = PMI, y = TTC-stained area / total myocardial area, R =
      0.5673). Samples with old myocardial infarction produced clear TTC contrast;
      normal tissue is vivid red, and fibrotic myocardium is white discoloration. In
      acute myocardial infarction cases where death occurred within 9 hours after the
      attack, however, the detection of infarcted area was very difficult even when PMI
      was less than 1.5 days. In summary, the TTC method may be useful within 1.5 days
      after death, but short suffering period before death disturbs its staining
      efficiency. 

PMID- 23949141
TI  - Fatal pediatric head injuries: a 20-year review of cases through the Auckland
      coroner's office.
AB  - Inflicted pediatric head injury is a significant issue in New Zealand, fatal
      cases receiving extensive media attention. The primary aims of this article were
      to analyze injury patterns and reported mechanisms against both age and cause
      (accidental or inflicted). The secondary aims were to quantify these deaths and
      identify trends over time. We retrospectively reviewed pediatric deaths due to
      head injury in children younger than 15 years referred to the Coronial Service of
      Auckland, New Zealand, from January 1, 1991, to December 31, 2010. One hundred
      sixty-seven cases were identified. Overall incidence was stable over time;
      however, the rate of inflicted head injury increased significantly (from 0.1 to
      0.4/100,000 per year). Evidence of impact was seen in 90% of cases. In children
      younger than 2 years, in the absence of motor vehicle or pedestrian trauma,
      subdural hemorrhage and diffuse axonal injury were both highly suggestive of
      inflicted injury. The absence of a history of trauma or a history of a fall less
      than 1 m was also highly suggestive of inflicted injury. Retinal hemorrhages in
      these fatal head injuries were severe in 77% of cases and moderate in the
      remainder. 

PMID- 23949142
TI  - Implementation of a departmental picture archiving and communication system: a
      productivity and cost analysis.
AB  - BACKGROUND: Digital radiology enhances productivity and results in long-term cost
      savings. However, the viewing, storage, and sharing of outside imaging studies on
      compact discs at ambulatory offices and hospitals pose a number of unique
      challenges to a surgeon's efficiency and clinical workflow. OBJECTIVE: To improve
      the efficiency and clinical workflow of an academic neurosurgical practice when
      evaluating patients with outside radiological studies. METHODS: Open-source
      software and commercial hardware were used to design and implement a departmental
      picture archiving and communications system (PACS). RESULTS: The implementation
      of a departmental PACS system significantly improved productivity and enhanced
      collaboration in a variety of clinical settings. Using published data on the rate
      of information technology problems associated with outside studies on compact
      discs, this system produced a cost savings ranging from $6250 to $33600 and from
      $43200 to $72000 for 2 cohorts, urgent transfer and spine clinic patients,
      respectively, therefore justifying the costs of the system in less than a year.
      CONCLUSION: The implementation of a departmental PACS system using open-source
      software is straightforward and cost-effective and results in significant gains
      in surgeon productivity when evaluating patients with outside imaging studies.

PMID- 23949146
TI  - Industry progress report on neuro-oncology: Biotech update 2013.
AB  - For the second time, The Brain Tumor Center of the Weill Cornell Brain and Spine
      Center, in collaboration with Voices Against Brain Cancer, hosted The Brain Tumor
      Biotech Summit in New York City in June 2013. After a very successful first
      summit in 2012, this innovative event has established a platform for intensive
      networking between neuro-oncologists, neurosurgeons, neuroscientists, members of
      the biotechnology and pharmaceutical communities, members of the financial
      community and leaders of non-profit organizations. This year's summit highlighted
      dendritic cell vaccines, novel antibody, heat shock protein and targeted
      therapies as well as exosome technologies, MRI-guided therapies and other novel
      drug delivery tools. This report presents a short overview of the current
      progress in brain tumor research and therapy as presented at the 2013 Brain Tumor
      Biotech Summit.

PMID- 23949147
TI  - Long-term safety and efficacy of donepezil in patients with dementia with Lewy
      bodies: results from a 52-week, open-label, multicenter extension study.
AB  - BACKGROUND/AIMS: To investigate the safety and efficacy of long-term
      administration (52 weeks) of donepezil in patients with dementia with Lewy bodies
      (DLB). METHODS: This was a 52-week, multicenter, open-label extension study. Up
      to 8 weeks after the completion of the preceding randomized, placebo-controlled
      trial (RCT), patients started treatment with 3 mg of donepezil daily for 2 weeks,
      followed by 5 mg daily for the remaining 50 weeks. Cognitive function, behavioral
      and psychiatric symptoms, cognitive fluctuations, and caregiver burden were
      assessed using the Mini-Mental State Examination, Neuropsychiatric Inventory,
      Cognitive Fluctuation Inventory, and the Zarit Caregiver Burden Interview,
      respectively. Safety parameters were monitored throughout. RESULTS: In total, 108
      patients were enrolled in the study. Cognitive function and dementia-related
      behavioral symptoms, including cognitive fluctuations, were improved after the
      start of donepezil treatment, and improvement was maintained for 52 weeks.
      Reduction in caregiver burden observed in the preceding RCT returned to the
      baseline level at 52 weeks. There was no significant imbalance in the incidence
      of adverse events (AEs) by onset time, and delayed AE onset induced by the long
      term administration of donepezil was unlikely to appear. CONCLUSION: The long
      term administration of donepezil at 5 mg/day was well tolerated in patients with
      DLB and is expected to exhibit lasting effects, improving impaired cognitive
      function and psychiatric symptoms up to 52 weeks.

PMID- 23949148
TI  - Neuropsychological assessments in patients with aneurysmal subarachnoid
      hemorrhage, perimesencephalic SAH, and incidental aneurysms.
AB  - Subarachnoid hemorrhage (SAH) is known to be associated with long-term cognitive
      deficits. Neurosurgical manipulation on the brain itself has been reported to
      have influence on neuropsychological sequelae. The following is a comparative
      study on perimesencephalic and aneurysmal subarachnoid hemorrhage patients as
      well as elective aneurysm patients that was carried out to determine the isolated
      and combined impact of surgical manipulation and hemorrhage, respectively, on
      long-term neuropsychological outcome. Inclusion criteria were good neurological
      recovery at discharge (modified Rankin Scale 0 or 1) without focal neurological
      deficit. Standardized psychological testing covered attention, memory, executive
      functions, and mood. Thirteen aneurysmal SAH patients, 15 patients undergoing
      elective clipping, and 14 patients with perimesencephalic SAH were analyzed.
      Standardized neuropsychological testing and social/professional history
      questionnaires were performed 2 years (mean) after discharge. Memory impairment
      and slower cognitive processing were found in the aneurysmal and
      perimesencephalic SAH groups, while elective aneurysm patients showed signs of
      impaired attention. However, compared with norm data for age-matched healthy
      controls, all groups showed no significant test results. In contrast, signs of
      clinical depression were seen in 9/42 patients, 45 % of all patients complained
      of stress disorders and 55 % of patients were unable to work in their previous
      professions. Nearly normal neuropsychological test results on long-term follow-up
      in SAH patients were unexpected. However, a 50 % rate of unemployment accompanied
      with stress disorders and depression manifests insufficient social and workplace
      reintegration. Therefore, even more specific rehabilitation programs are required
      following inpatient treatment to attain full recovery. 

PMID- 23949149
TI  - Reply: Comment on 'Childhood leukaemia close to high-voltage power lines--the
      Geocap study, 2002-2007'--odds ratio and confidence interval.

PMID- 23949150
TI  - Comment: childhood leukaemia and power lines--the Geocap study: is proximity an
      appropriate MF exposure surrogate?

PMID- 23949151
TI  - Loss of PTEN expression is an independent predictor of favourable survival in
      endometrial carcinomas.
AB  - BACKGROUND: We and others previously reported the prognostic significance of PTEN
      mutational status on favourable survival in endometrial carcinomas. Here, we
      demonstrate that loss of PTEN expression in immunohistochemistry is an
      independent prognostic marker for favourable survival in endometrial carcinomas.
      METHODS: We conducted immunohistochemical analyses of PTEN, PIK3CA,
      phosphorylated Akt (p-Akt), and p27 in primary endometrial carcinomas from 221
      patients. Mutation of PTEN was analysed further. RESULTS: Expression of PTEN was
      lost in 56 patients (25%), and PIK3CA was overexpressed in 159 patients (72%).
      Overexpression of PIK3CA was associated with p-Akt overexpression (P<0.001),
      which was in turn associated with loss of nuclear p27 expression (P=0.028). Loss
      of PTEN expression was found to be associated with endometrioid histology
      (P=0.03), and was inversely associated with the presence of lymphovascular space
      invasion (P=0.03). Univariate and multivariate survival analyses revealed that
      factors of PTEN loss, age <70, histological grade 1, early International
      Federation of Gynecology and Obstetrics (FIGO) stage, and absence of
      lymphovascular invasion were independent prognostic indicators for better overall
      survival (P=0.03, 0.04, 0.01, <0.001, and 0.03, respectively). The subset
      analysis showed a stronger tendency of PTEN loss towards favourable survival in
      advanced-stage (III and IV) disease than in early-stage (I and II) disease
      (P=0.05 vs 0.14). Moreover, our mutational analysis demonstrated that PTEN
      expression loss was associated with PTEN-truncating mutations (P=0.03).
      CONCLUSION: The current observations further support the prognostic significance
      of PTEN aberration on favourable outcome in endometrial carcinomas, providing
      useful implications for the individualised management of the disease.

PMID- 23949152
TI  - External validation of an online nomogram in patients undergoing radical
      nephroureterectomy for upper urinary tract urothelial carcinoma.
AB  - BACKGROUND: The objective was to validate an online nomogram developed based on
      the French collaborative national database on upper urinary tract urothelial
      carcinoma (UUT-UC) using a different cohort. METHODS: The study comprised 328
      patients with UUT-UC who underwent radical nephroureterectomy. The discrimination
      of models was quantified using Harrell's concordance index. The relationship
      between the model-derived and actuarial cancer-specific mortality was graphically
      explored within calibration plots. Calibration was also assessed using the
      quartiles of the predicted survival at 3 and 5 years and calculation of the
      corresponding observed Kaplan-Meier estimates. Clinical net benefit was evaluated
      constructing decision curve analysis. RESULTS: The discrimination accuracy of the
      nomograms at 3 and 5 years was 71.6% and 71.8%, respectively. Although nomograms
      discriminated well by Kaplan-Meier curves, and log-rank tests were all highly
      significant, the calibration plots tended to exaggerate the overestimation of
      mortality between predicted and observed probabilities at 3 and 5 years for
      survival. When compared with the AJCC/UICC staging system, the nomograms
      performed well across a wide range of threshold probabilities using decision
      curve analysis. CONCLUSION: The online nomogram is a highly accurate prognostic
      tool for patients with UUT-UC treated with radical nephroureterectomy. The model
      can provide an accurate estimate of the individual risk of cancer-specific
      mortality. Further improvement and implementation of novel molecular marker is
      needed.

PMID- 23949153
TI  - The value of high adherence to tamoxifen in women with breast cancer: a community
      based cohort study.
AB  - BACKGROUND: Low adherence to adjuvant tamoxifen is associated with worse health
      outcomes but little is known about the cost-effectiveness of high adherence.
      METHODS: We conducted an economic evaluation using data for all women with
      incident breast cancer between 1993 and 2000 who were subsequently prescribed
      tamoxifen in the Tayside region of Scotland. Patient-level, lifetime Markov
      models evaluated the impact of high vs low adherence to tamoxifen using linked
      prescribing, cancer registry, clinical cancer audit, hospital discharge and death
      records. Direct medical costs were estimated for each patient and quality-of-life
      weights were assigned. Recurrence information was collected by case note review
      and adherence calculated from prescribing records with low adherence classed
      below 80%. RESULTS: A total of 354 (28%) patients had a recorded recurrence and
      504 (39%) died. Four hundred and seventy-five (38%) patients had low adherence
      over the treatment period, which was associated with reduced time to recurrence
      of 52% (P<0.001). Time to other cause mortality was also reduced by 23% (P=0.055)
      but this was not statistically significant. For an average patient over her
      lifetime, low adherence was associated with a loss of 1.43 (95% CI: 1.15-1.71)
      discounted life years or 1.12 (95% CI: 0.91-1.34) discounted quality-adjusted
      life years (QALYs) and increased discounted medical costs of L5970 (95% CI: L4644
      L7372). Assuming a willingness to pay threshold of L25,000 per QALY, the expected
      value of changing a patient from low to high adherence is L33,897 (95% CI:
      L28,322-L39,652). CONCLUSION: Patients with low adherence have shorter time to
      recurrence, increased medical costs and worse quality of life. Interventions that
      encourage patients to continue taking their treatment on a daily basis for the
      recommended 5-year period may be highly cost-effective.

PMID- 23949155
TI  - Comment on 'Childhood leukaemia close to high-voltage power lines--the Geocap
      study, 2002-2007'--odds ratio and confidence interval.

PMID- 23949154
TI  - Effects of platelet-activating factor and its differential regulation by
      androgens and steroid hormones in prostate cancers.
AB  - BACKGROUND: Platelet-activating factor (PAF) is an arachidonic acid metabolite
      that plays an important role in cell proliferation, migration and
      neoangiogenesis, but whether it is involved in the progression of prostate cancer
      remains undiscovered. METHODS: Clinical prostate specimens were investigated with
      immunohistochemistry method and in vitro cell experiments referred to MTS cell
      proliferation assay, invasion and migration experiment, quantitative real-time RT
      PCR assay, western blotting analysis and ELISA assay. RESULTS: Platelet
      activating factor synthetase, lyso-PAF acetyl transferase (LPCAT1), increased
      significantly in castration-resistant prostate cancer (CRPC) specimens and CRPC
      PC-3 cells than that in controls. Intriguingly, PAF induced invasion and
      migration of PC-3 cells but not LNCaP cells. The PAF receptor antagonist
      inhibited proliferation of LNCaP and PC-3 cells. Dihydrotestosterone (DHT)
      treatment caused a decrease in LPCAT1 expression and PAF release in LNCaP cells,
      which could be blocked by androgen receptor antagonists. Finally, DHT increased
      LPCAT1 expression and PAF release in PC-3 cells in a Wnt/beta-catenin-dependent
      manner. CONCLUSION: For the first time, our data supported that PAF might play
      pivotal roles in the progression of prostate cancer, which might throw a new
      light on the treatment of prostate cancer and the prevention of the emergence of
      CRPC.

PMID- 23949156
TI  - Reply: comment on 'Childhood leukaemia close to high-voltage power lines--the
      Geocap study, 2002-2007'--is proximity an appropriate MF exposure surrogate?

PMID- 23949157
TI  - Encapsulation of supported metal nanoparticles with an ultra-thin porous shell
      for size-selective reactions.
AB  - A novel nanostructured catalyst with an ultra-thin porous shell obtained from the
      thermal decomposition of an aluminium alkoxide film deposited by molecular layer
      deposition for size-selective reactions was developed. The molecular sieving
      capability of the porous metal oxide films was verified by examining the liquid
      phase hydrogenation of n-hexene versus cis-cyclooctene. 

PMID- 23949158
TI  - Intrinsic electronic and transport properties of graphyne sheets and nanoribbons.
AB  - Graphyne, a two-dimensional carbon allotrope like graphene but containing doubly
      and triply bonded carbon atoms, has been proven to possess amazing electronic
      properties as graphene. Although the electronic, optical, and mechanical
      properties of graphyne and graphyne nanoribbons (NRs) have been previously
      studied, their electron transport behaviors have not been understood. Here we
      report a comprehensive study of the intrinsic electronic and transport properties
      of four distinct polymorphs of graphyne (alpha, beta, gamma, and 6,6,12
      graphynes) and their nanoribbons (GyNRs) using density functional theory coupled
      with the non-equilibrium Green's function (NEGF) method. Among the four graphyne
      sheets, 6,6,12-graphyne displays notable directional anisotropy in the transport
      properties. Among the GyNRs, those with armchair edges are nonmagnetic
      semiconductors whereas those with zigzag edges can be either antiferromagnetic or
      nonmagnetic semiconductors. Among the armchair GyNRs, the alpha-GyNRs and 6,6,12
      GyNRs exhibit distinctive negative differential resistance (NDR) behavior. On the
      other hand, the zigzag alpha-GyNRs and zigzag 6,6,12-GyNRs exhibit symmetry
      dependent transport properties, that is, asymmetric zigzag GyNRs behave as
      conductors with nearly linear current-voltage dependence, whereas symmetric GyNRs
      produce very weak currents due to the presence of a conductance gap around the
      Fermi level under finite bias voltages. Such symmetry-dependent behavior stems
      from different coupling between pi* and pi subbands. Unlike alpha- and 6,6,12
      GyNRs, both zigzag beta-GyNRs and zigzag gamma-GyNRs exhibit NDR behavior
      regardless of the symmetry. 

PMID- 23949159
TI  - Contrasting effects of chronic, systemic treatment with mTOR inhibitors rapamycin
      and metformin on adult neural progenitors in mice.
AB  - The chronic and systemic administration of rapamycin extends life span in
      mammals. Rapamycin is a pharmacological inhibitor of mTOR. Metformin also
      inhibits mTOR signaling but by activating the upstream kinase AMPK. Here we
      report the effects of chronic and systemic administration of the two mTOR
      inhibitors, rapamycin and metformin, on adult neural stem cells of the
      subventricular region and the dendate gyrus of the mouse hippocampus. While
      rapamycin decreased the number of neural progenitors, metformin-mediated
      inhibition of mTOR had no such effect. Adult-born neurons are considered
      important for cognitive and behavioral health, and may contribute to improved
      health span. Our results demonstrate that distinct approaches of inhibiting mTOR
      signaling can have significantly different effects on organ function. These
      results underscore the importance of screening individual mTOR inhibitors on
      different organs and physiological processes for potential adverse effects that
      may compromise health span. 

PMID- 23949161
TI  - Membrane-less hydrogen bromine flow battery.
AB  - In order for the widely discussed benefits of flow batteries for electrochemical
      energy storage to be applied at large scale, the cost of the electrochemical
      stack must come down substantially. One promising avenue for reducing stack cost
      is to increase the system power density while maintaining efficiency, enabling
      smaller stacks. Here we report on a membrane-less hydrogen bromine laminar flow
      battery as a potential high-power density solution. The membrane-less design
      enables power densities of 0.795 W cm(-2) at room temperature and atmospheric
      pressure, with a round-trip voltage efficiency of 92% at 25% of peak power.
      Theoretical solutions are also presented to guide the design of future laminar
      flow batteries. The high-power density achieved by the hydrogen bromine laminar
      flow battery, along with the potential for rechargeable operation, will translate
      into smaller, inexpensive systems that could revolutionize the fields of large
      scale energy storage and portable power systems.

PMID- 23949160
TI  - Impact of whole-body electromyostimulation on body composition in elderly women
      at risk for sarcopenia: the Training and ElectroStimulation Trial (TEST-III).
AB  - Most studies have confirmed the positive impact of resistance training on muscle
      mass and functional capacity in aging adults. However, due to physical limitation
      or a simple aversion against regular exercise, the majority of elderly subjects
      do not reach the exercise doses recommended for impacting strength or muscle
      mass. This led us to evaluate the effect of whole-body electromyostimulation (WB
      EMS), a novel, time-efficient and smooth training technology, on body composition
      with special regard to sarcopenia. Seventy-six lean, non-sportive women (75 +/- 4
      years) were randomly assigned to either a WB-EMS group (WB-EMS, n = 38) that
      performed 18 min of WB-EMS (bipolar, 85 Hz) 3 sessions in 14 days (1.5
      sessions/week) or a semi-active control group (aCG, n = 38). Body composition was
      assessed by dual-energy X-ray absorptiometry and maximum strength was evaluated
      using isometric techniques for trunk and legs. After 54 weeks of intervention,
      significant inter-group differences were determined for appendicular skeletal
      muscle mass (WB-EMS, 0.4 +/- 2.2 % vs. aCG, -1.5 +/- 3.1 %; p = 0.009), lean body
      mass (WB-EMS, 0.8 +/- 1.8 % vs. aCG, -0.8 +/- 2.7 %; p = 0.008) and maximum
      isometric strength (leg extensors, 9.8 +/- 12.9 % vs. 0.2 +/- 10.4 %; p = 0.003;
      trunk extensors, 10.1 +/- 12.7 vs. -1.6 +/- 8.6 %; p = 0.001). Although
      borderline significant for abdominal fat mass (WB-EMS, -2.9 +/- 8.3 vs. aCG, 1.5
      +/- 10.7 %; p = 0.069), differences did not reach statistically significant
      levels for body fat parameters. Considering the clinical effectiveness for
      impacting sarcopenia and the good acceptance of this technology by this non
      sportive cohort of elderly women, we conclude that for elderly subjects unable or
      unwilling to perform dynamic strength exercises, electromyostimulation may be a
      less off-putting alternative to maintain lean body mass and strength.

PMID- 23949162
TI  - Sponges and incorrect sponge count: Minor contributions to the process of
      detecting retained foreign bodies.
AB  - Background: Postoperative retained foreign bodies [RFBs] can be a serious event,
      but they are rare. The x-ray is the current gold standard to detect RFBs. There
      has been scant research on the process of detection as opposed to the consequence
      of RFBs. Surgical sponges incorporating automatic data identity capture
      technology (radiofrequency tags, barcodes) have been proposed to detect RFBs.
      Because resources in healthcare are scarce, careful consideration needs to be
      given to developing the right technology in order to maximize the process of RFB
      elimination. There have been few studies that identify factors contributing to
      the process of RFB detection. Study design: Our goal was to determine the
      frequency with which x-rays were ordered to detect abdominal surgery post
      operative RFBs and the indications for ordering them. We reviewed the Johns
      Hopkins Hospital's Department of Radiology database to retrospectively study the
      demographic and radiologic data on patients who underwent exploratory surgery for
      RFBs following abdominal procedures performed between April 2004 and April 2008.
      Results: Of the 13,335 portable abdominal x-rays taken during the period, 203
      (1.5%) were ordered to assess patients for the presence of an RFB. Of these, 57
      (28%) were taken because no RFB count was made (e.g., for emergency procedures),
      57 (28%) were taken per procedure or protocol, 51 (25%) were taken because of an
      incorrect instrument count, and 39 (19%) were taken because of an incorrect
      sponge count. Of the 203 x-rays, 192 (95%) were negative for RFBs, 11 (5%) were
      positive or had suspicious findings, and of these 3 (2%) revealed more than 1
      RFB. The 11 patients with positive or suspicious findings underwent exploratory
      procedures immediately during the same operation; of these, 8 (72%) actually had
      an RFB and 3 (28%) had a negative result at exploration. Conclusion: Multiple
      pathways lead to the decision to obtain X-rays for RFBs, of which
      sponges/Incorrect sponge counts make up only one in five. Therefore, technology
      that focuses on sponges alone may not majorly impact clinical outcome because x
      rays will still be required in the majority of cases of suspected high risk.

PMID- 23949163
TI  - Biodegradable metallic materials for orthopaedic implantations: A review.
AB  - Non-degradable metals such as stainless steel, cobalt-chromium-based alloys,
      titanium and its alloys may lead to stress shielding effect after fractured bone
      has healed. This complication may attribute to the non-degradability and the
      mismatch of the mechanical properties between these metallic implants and human
      bone. Biodegradable metallic materials have been therefore studied as alternative
      implantable metals in orthopaedics for some years. Magnesium is a potential
      candidate, as its mechanical properties are similar to human. Additionally, it is
      degradable and its ions are essential for cell functions. However, rapid
      degradation and release of hydrogen gas may inhibit its applications clinically.
      Hence, this paper reviews the development of the biodegradable metallic implants
      and various methods to improve the degradation of magnesium alloys.

PMID- 23949172
TI  - Biomechanical comparison of three types of bone graft for anterior spondylodesis.
AB  - BACKGROUND: Anterior spondylodesis with bone grafting for fusion of spinal motion
      segments is a common procedure in clinical routine. Bone grafts for fusion
      include autologous, allogenic and xenogenic grafts that are inserted in the
      unstable spinal motion segment. Nevertheless, biomechanical data for autologous,
      allogenic and xenogenic grafts are rare. OBJECTIVE: The purpose of this study was
      to conduct biomechanical comparison of native and conserved bone grafts used in
      spondylodesis of the spine. METHODS: Grafts examined were native ovine
      tricortical iliac crest grafts, bovine cancellous bone blocks and ovine,
      tricortical iliac crest grafts, conserved in the same way as the bovine
      cancellous bone blocks. The grafts were tested biomechanically to failure.
      Compared parameters were maximum torque, maximum rotation angle and graft
      stiffness at failure. The Mann-Whitney-U test with Bonferroni adjustment was used
      for statistical analysis. RESULTS: Maximum torque at failure of the bovine
      cancellous bone graft did not differ significantly from that of the native ovine
      tricortical graft. Comparison of the conserved ovine tricortical graft revealed
      significantly lower values compared to the native ovine tricortical bone
      graft.Maximum rotation angle at failure of the untreated ovine tricortical bone
      grafts was significantly higher compared to the other grafts tested. Regarding
      graft stiffness no significant differences were found. CONCLUSIONS: Based on the
      functional demands exerted on the spinal motion segment, our results suggest that
      torsional strength and deformational behavior of the bone graft influence the
      stability of the spondylodesis. The native tricortical graft best fulfills this
      requirement.

PMID- 23949173
TI  - Flow observations in elastic stenosis biomodel with comparison to rigid-like
      model.
AB  - BACKGROUND: Plaques in blood vessels exhibit a wide range of stiffness depending
      on disease conditions: stiffness is an important factor in plaque behavior. The
      geometrical change in plaque based on its behavior can affect blood flow
      patterns. Thus, it is important to study both blood flow and deformation of
      plaques and blood vessels. OBJECTIVE: This study aims to identify the differences
      in flow conditions between in vitro models to discuss experimental materials for
      arterial wall and flow observation. METHODS: In order to observe the blood flow
      pattern and plaque deformation simultaneously, a PVA-H stenosis model was used.
      In addition, a silicone model was also used as a rigid-like model for comparison
      with the PVA-H model. PIV was employed to measure the flow velocity distribution
      and determine the flow levels in the models. RESULTS: PVA-H model exhibits
      expansion with an increase in upstream pressure and silicone model maintains the
      diameter. The expansion depends on their mechanical properties and influences
      flow conditions such as velocity changes and RAP in the parent artery. The
      balance between the expansion and change in flow conditions determines the final
      geometries of PVA-H model and flow pattern. CONCLUSIONS: The results suggest that
      the stiffness measurement for blood vessels and plaques such as ultrasound
      measurements would be important for accurate treatments.

PMID- 23949174
TI  - Classification of sleep apnea using wavelet-based spectral analysis of heart rate
      variability.
AB  - BACKGROUND: Obstructive Sleep Apnea (OSA) is the cessation of breathing during
      sleep due to the collapse of upper airway. Polysomnographic recording is a
      conventional method for detection of OSA. Although it provides reliable results,
      it is expensive and cumbersome. Thus, an advanced non-invasive signal processing
      based technique is needed. OBJECTIVE: The main purpose of this work is to predict
      the severity of sleep apnea using an efficient wavelet-based spectral analysis
      method of the heart rate variability (HRV) to classify sleep apnea into three
      different levels (mild, moderate, and severe) according to its severity and to
      distinguish them from normal subjects. METHODS: The standard FFT spectrum
      analysis method and the soft-decision wavelet-based technique are to be used in
      this work in order to rank patients to full polysomnography. Data of 20 normal
      subjects and 20 patients with mild apnea and 20 patients with moderate apnea and
      20 patients of severe apnea are used in this study. The data is obtained from the
      sleep laboratory of Sultan Qaboos University hospital in Oman. Four different
      classification versions have been used in this work. RESULTS: Accuracy result of
      90% was obtained between severe and normal subjects and 85% between mild and
      normal and 75% between severe and moderate and 83.75% between normal and
      patients. CONCLUSIONS: The VLF/LF power spectral ratio of the wavelet-based soft
      decision analysis of the RRI data after a high-pass filter resulted in the best
      accuracy of classification in all versions.

PMID- 23949175
TI  - Space radiobiology and the new era of induced radioresistance: should traditional
      concepts be moved to science history museums?
AB  - Energetic solar particle events (SPE) which are among the main sources of
      ionizing radiation can be life threatening to astronauts who are not adequately
      protected. To date, physical shielding of spacecrafts and inducing
      radioresistance by using radioprotectors have been proposed by different
      investigators. Mortazavi et al. have previously reported that screening of the
      candidates of long-term space missions by conducting Ground-based in vitro
      adaptive response studies before any mission identifies the individuals who
      respond well to low levels of ionizing radiation and reveal high magnitudes of
      radioadaptive response. On the other hand, Mortazavi et al. have recently showed
      that radiofrequency-induced adaptive response can be used as a method for
      decreasing the risk of infection caused by immunosuppression during deep space
      missions. Furthermore, over the past years the radioresistance induced by a wide
      variety of radioprotectors has been studied. According to classical radiobiology,
      chemical radioprotective agents must be administered before irradiation or at the
      time of irradiation, to increase the mean survival rate of the exposed
      individuals. A revolution in this paradigm was started in 2010, when
      investigators reported that a diet supplemented with antioxidants administered
      starting 24 h after total-body irradiation is more effective than if given soon
      after the exposure (radiation mitigation). This finding along with the above
      mentioned interventions open new horizons in inducing biological radioresistance
      against unpredictable high levels of radiation due to solar particle events. This
      wide time window indeed enables astronauts to firstly evaluate their radiation
      doses before making any decision on the type of intervention. As major solar
      particle events last for hours, astronauts will be able to consult distinguished
      radiation biologists via satellite telecommunication before choosing any medical
      intervention. 

PMID- 23949176
TI  - Teleconsultation of coronary angiograms using smartphones and an audio/video
      conferencing application.
AB  - OBJECTIVE: To examine the feasibility and accuracy of teleconsultation of
      coronary angiograms using iPhone 4 and FaceTime. METHODS: The study was conducted
      in two stages. Coronary angiograms of 100 patients with single-vessel disease
      were retrospectively selected by a core laboratory unit and then re-evaluated by
      a consultant cardiologist on both an iPhone 4 screen via the FaceTime application
      and on the workstation monitor of the angiography laboratory. The interpretations
      of the consultant cardiologist on localization and severity of angiographic
      lesions were recorded and compared with those of the core laboratory. Using the
      same teleconsultation system, the consultant cardiologist outside the hospital
      was presented live angiographic images of 10 patients undergoing primary
      percutaneous coronary intervention (PCI) for acute myocardial infarction.
      RESULTS: Interpretations of the consultant cardiologist on the localization and
      severity of 100 lesions on both the smartphone screen and workstation monitor
      showed high levels of agreement with the results of the core laboratory (for all,
      kappa > 0.80). Of 10 patients whose PCI was performed under live video
      teleconsultation, eight patients underwent successful PCI while two patients had
      normal coronary arteries. There was an excellent agreement between the consultant
      cardiologist and the operator regarding lesion localization. CONCLUSIONS:
      Smartphones allow highly accurate interpretations on angiographic lesions and
      thus may serve as a supplementary teleconsultation tool in both elective and
      emergency situations.

PMID- 23949178
TI  - Correlation between Reynolds number and eccentricity effect in stenosed artery
      models.
AB  - BACKGROUND: Flow recirculation and shear strain are physiological processes
      within coronary arteries which are associated with pathogenic biological
      pathways. Distinct Quite apart from coronary stenosis severity, lesion
      eccentricity can cause flow recirculation and affect shear strain levels within
      human coronary arteries. OBJECTIVE: The aim of this study is to analyse the
      effect of lesion eccentricity on the transient flow behaviour in a model of a
      coronary artery and also to investigate the correlation between Reynolds number
      (Re) and the eccentricity effect on flow behaviour. METHODS: A transient particle
      image velocimetry (PIV) experiment was implemented in two silicone based models
      with 70% diameter stenosis, one with eccentric stenosis and one with concentric
      stenosis. RESULTS: At different times throughout the flow cycle, the eccentric
      model was always associated with a greater recirculation zone length, maximum
      shear strain rate and maximum axial velocity; however, the highest and lowest
      impacts of eccentricity were on the recirculation zone length and maximum shear
      strain rate, respectively. Analysis of the results revealed a negative
      correlation between the Reynolds number (Re) and the eccentricity effect on
      maximum axial velocity, maximum shear strain rate and recirculation zone length.
      CONCLUSIONS: As Re number increases the eccentricity effect on the flow behavior
      becomes negligible.

PMID- 23949179
TI  - A neural network approach for feature extraction and discrimination between
      Parkinsonian tremor and essential tremor.
AB  - BACKGROUND: Essential tremor (ET) and the tremor in Parkinson's disease (PD) are
      the two most common pathological tremor with a certain overlap in the clinical
      presentation. OBJECTIVE: The main purpose of this work is to use an artificial
      neural network to select the best features and to discriminate between the two
      types of tremors using spectral analysis of tremor time-series recorded by
      accelerometry and surface EMG signals. METHODS: The Soft-Decision wavelet-based
      technique is to be used in this work in order to obtain a 16 bands approximate
      spectral representation of both accelerometer and two EMG signals of two sets of
      data (training and test). The training set consists of 21 ET subjects and 19 PD
      subjects while the test set consists of 20 ET and 20 PD subjects. The data has
      been recorded for diagnostic purposes in the Department of Neurology of the
      University of Kiel, Germany. A neural network of the type feed forward back
      propagation has been used to find the frequency bands associated with the
      different signals that yield better discrimination efficiency on training data.
      The same designed network is used to discriminate the test set. RESULTS:
      Efficiency result of 87.5% was obtained using two different bands from each of
      the three signals under test. CONCLUSIONS: The artificial neural network has been
      used successfully in both feature extraction and in pattern matching tasks in a
      complete classification system.

PMID- 23949180
TI  - A study into the automation of cognitive assessment tasks for delivery via the
      telephone: lessons for developing remote monitoring applications for the elderly.
AB  - BACKGROUND: Cognitive assessments are valuable tools in assessing neurological
      conditions. They are critical in measuring deficits in cognitive function in an
      array of neurological disorders and during the ageing process. Automation of
      cognitive assessments is one way to address the increasing burden on medical
      resources for an ever increasing ageing population. OBJECTIVE: This study
      investigated the suitability of using automated Interactive Voice Response (IVR)
      technology to deliver a suite of cognitive assessments to older adults using
      speech as the input modality. METHODS: Several clinically valid and gold-standard
      cognitive assessments were selected for implementation in the IVR application.
      The IVR application was designed using human centred design principles to ensure
      the experience was as user friendly as possible. Sixty one participants completed
      two IVR assessments and one face to face (FF) assessment with a
      neuropsychologist. Completion rates for individual tests were inspected to
      identify those tests that are most suitable for administration via IVR
      technology. Interclass correlations were calculated to assess the reliability of
      the automated administration of the cognitive assessments across delivery modes.
      RESULTS: While all participants successfully completed all automated assessments,
      variability in the completion rates for different cognitive tests was observed.
      Statistical analysis found significant interclass correlations for certain
      cognitive tests between the different modes of administration. Analysis also
      suggests that an initial FF assessment reduces the variability in cognitive test
      scores when introducing automation into such an assessment. CONCLUSION:
      [corrected] This study has demonstrated the functional and cognitive reliability
      of administering specific cognitive tests using an automated, speech driven
      application. This study has defined the characteristics of existing cognitive
      tests that are suitable for such an automated delivery system and also informs on
      the limitations of other cognitive tests for this modality. This study presents
      recommendations for developing future large scale cognitive assessments.

PMID- 23949177
TI  - Automated assessment of cognitive health using smart home technologies.
AB  - BACKGROUND: The goal of this work is to develop intelligent systems to monitor
      the wellbeing of individuals in their home environments. OBJECTIVE: This paper
      introduces a machine learning-based method to automatically predict activity
      quality in smart homes and automatically assess cognitive health based on
      activity quality. METHODS: This paper describes an automated framework to extract
      set of features from smart home sensors data that reflects the activity
      performance or ability of an individual to complete an activity which can be
      input to machine learning algorithms. Output from learning algorithms including
      principal component analysis, support vector machine, and logistic regression
      algorithms are used to quantify activity quality for a complex set of smart home
      activities and predict cognitive health of participants. RESULTS: Smart home
      activity data was gathered from volunteer participants (n=263) who performed a
      complex set of activities in our smart home testbed. We compare our automated
      activity quality prediction and cognitive health prediction with direct
      observation scores and health assessment obtained from neuropsychologists. With
      all samples included, we obtained statistically significant correlation (r=0.54)
      between direct observation scores and predicted activity quality. Similarly,
      using a support vector machine classifier, we obtained reasonable classification
      accuracy (area under the ROC curve=0.80, g-mean=0.73) in classifying participants
      into two different cognitive classes, dementia and cognitive healthy.
      CONCLUSIONS: The results suggest that it is possible to automatically quantify
      the task quality of smart home activities and perform limited assessment of the
      cognitive health of individual if smart home activities are properly chosen and
      learning algorithms are appropriately trained.

PMID- 23949181
TI  - Reliability and concurrent validity of bathroom weighing scale and
      sphygmomanometer in quantifying magnitude of digital postero-anterior spinal
      pressure.
AB  - PURPOSE: The main objective of this study was to determine the reliability and
      concurrent validity of using Modified Sphygmomanometer (sphyg) and body weighing
      scale to determine the magnitude of pressure and body weight change during
      digital spinal examination. SUBJECTS: One hundred and twenty apparently healthy
      subjects were recruited. METHODS: Weighing scale was used to measure the body
      weight of the investigator while Mercury sphygmomanometer was used to measure the
      pressure exerted. There was test re-test interval of 2 weeks. Data were analysed
      by descriptive statistic and Pearson product moment correlation. RESULTS: The
      result showed that there was significant correlation between the weight change
      (WC) values obtained on the weighing scale on day 1 and 2 (r=0.91). Also, there
      was significant correlation between Pressure obtained in the sphygmomanometer on
      day 1 and 2 (r=0.94). Similarly, there was significant correlation between the WC
      and Pressure Change (PC), (r=-0.49). The participant's age, height, weight and
      BMI contributed significantly as predictors for both BWC and PC change
      respectively. CONCLUSION: This study concluded that weighing scale and Mercury
      sphygmomanometer are reliable and valid to determine the magnitude of pressure
      applied during DPAP.

PMID- 23949182
TI  - Muscle strength of the lumbar spine in different sports.
AB  - BACKGROUND: The ability to stabilize the body center (core stability) against
      dynamic movements of the extremities and capability to absorb repetitive loading
      forces in the trunk play a crucial role in any professional sport specific
      performance. OBJECTIVE: The aim our cross sectional level of evidence 3 study was
      to determine, if athletes of different sport disciplines showed specific trunk
      strength profiles and if these were different from a control group. METHODS: 20
      ironman triathletes, 18 amateur volleyball and 18 amateur soccer players were
      tested for their individual isometric strength of the lumbar spine in three
      planes of motion using a standartized test device. RESULTS: The test profile
      revealed similar strength parameters for extension and lateral flexion to the
      left in each of the 3 study groups tested. The lateral flexion to the right was
      significantly stronger than in the control group (soccer > volleyball >
      triathlon). In all 3 groups, weaknesses were found in the abdominal musculature,
      showing highly significant differences in flexion and bilateral rotation compared
      to the control group (p=0.001). CONCLUSIONS: Our study shows that sports specific
      training for triathlon, as well as the team sports soccer and volleyball, does
      not lead to balanced trunk musculature and core stability. In consequence
      predisposing injury and muscle dysbalane can trigger pain syndromes.

PMID- 23949183
TI  - Development of a model to mimic pleural space mechanics.
AB  - BACKGROUND: A simulator of the respiratory system which includes the pleural
      space is currently lacking. However, such mechanical models are essential to
      develop and test new medical devices regulating the pressure in the pleural
      space. OBJECTIVE: It was the aim of this study to develop a model which mimics
      the pleural space. The device should be able to represent biomechanical functions
      of the respiratory system and it is intended for applications in research and
      development to study pleural space mechanics. The system should allow adjusting
      parameters to simulate different kinds of breathing. Output parameters such as
      the pressure in pleural cavity or the breathing volume should be measured.
      METHODS: A mechanical lung simulator was developed. The chest wall is represented
      by an elastic shell in which silicone balloons were implemented to mimic the lung
      tissue. These two components establish a pleural cavity. Pressure sensors were
      installed to measure pressure in the pleural space and an aeroplethysmograph was
      positioned above the two lungs to measure flow. The system was assembled and
      tested under various conditions. RESULTS: Different tests demonstrated that the
      device is currently capable of simulating breathing volumes up to approx. 1700
      ml. Different breathing characteristics including coughing can be simulated.
      Higher negative pressures especially during deep breathing were observed at the
      top of the lung because of higher balloon wall (lung) thickness in this area. It
      was possible to demonstrate the effect of certain changes of the lung tissue such
      as fibrosis with corresponding pressure recordings confirming known effects of
      such pathologies. CONCLUSIONS: The device allows simulating pressures in the
      pleural space during breathing at an advanced level and will be of use to develop
      and validate medical devices under laboratory conditions that control and
      regulate the pleural space. This represents a significant benefit to improve the
      development process for devices in this area.

PMID- 23949184
TI  - Atomic sites and stability of Cs+ captured within zeolitic nanocavities.
AB  - Zeolites have potential application as ion-exchangers, catalysts and molecular
      sieves. Zeolites are once again drawing attention in Japan as stable adsorbents
      and solidification materials of fission products, such as (137)Cs(+) from damaged
      nuclear-power plants. Although there is a long history of scientific studies on
      the crystal structures and ion-exchange properties of zeolites for practical
      application, there are still open questions, at the atomic-level, on the physical
      and chemical origins of selective ion-exchange abilities of different cations and
      detailed atomic structures of exchanged cations inside the nanoscale cavities of
      zeolites. Here, the precise locations of Cs(+) ions captured within A-type
      zeolite were analyzed using high-resolution electron microscopy. Together with
      theoretical calculations, the stable positions of absorbed Cs(+) ions in the
      nanocavities are identified, and the bonding environment within the zeolitic
      framework is revealed to be a key factor that influences the locations of
      absorbed cations. 

PMID- 23949185
TI  - The potential lost hospital income from miscoded emergency department boarders in
      Ireland.
AB  - BACKGROUND: Emergency department (ED) boarders, namely patients who have been
      admitted under an in-patient service but remain on a trolley in the ED, have long
      been a problem in the Irish healthcare system. METHODS: We conducted a
      retrospective analysis of all ED boarders in Cork University Hospital (CUH) for a
      6-month period from January to July 2011. Data were obtained from the Hospital In
      Patient Enquiry Office (HIPE). The income generated by the hospital for a subset
      of these patients (January and February attendances) was obtained from the
      Finance Office in the hospital, based on diagnoses as recorded on the HIPE
      system. A convenience sample of two-thirds of the 39 acute hospitals nationally
      was surveyed to ascertain whether ED boarders were coded by individual HIPE
      offices as hospital in-patients or as ED attendees. RESULTS: A total of 806
      patients were admitted to an in-patient service from January to July 2011 in CUH
      and subsequently discharged, having completed their entire stay in the ED. The
      income generated by a sub-sample of 228 patients (January and February ED
      boarders) was determined. The hospital was remunerated by <euro>685,111 for these
      patients, i.e. an average income of <euro>3,098 per patient. Only 8 hospitals of
      the 27 surveyed hospitals coded overnight ED Boarders as in-patients and were
      thus able to request income for these patients appropriately. CONCLUSION:
      Discrepancies in coding of ED boarders may result in significant revenue losses
      for certain hospitals.

PMID- 23949186
TI  - The effect of oxygen vacancies on water wettability of a ZnO surface.
AB  - In this study, the effect of oxygen vacancies on the water wettability of a
      hydrated ZnO(100) surface has been examined via molecular dynamics simulations
      with a reactive force field (ReaxFF). The results show that the oxygen vacancies
      on the ZnO surface change the structures of the ZnO surface and subsequently its
      water adsorption capability. While a 1 : 1 ratio of water to hydroxyl is observed
      for a water monolayer absorbed on ZnO(100) without oxygen vacancies, additional
      water adsorption as coordinate hydroxyl that resides on the vacancy site and
      bonds with three lattice zinc atoms is observed on the surfaces with oxygen
      vacancies. The results also show that the energy of the interaction per unit area
      between water and the hydrated ZnO surface is 55.1% higher in the presence of the
      oxygen vacancies than that without oxygen vacancies. This leads to a water
      contact angle of ~115 degrees  for the hydrated ZnO(100) surface in the absence
      of vacancies and ~21 degrees  with vacancies. The wetting kinetics of a water
      droplet on a ZnO(100) surface with and without oxygen vacancies are compared with
      the diffusion-limited reactive wetting and molecular kinetics models,
      respectively. In addition, the ordering of the vacancy sites is found not to
      significantly affect the wettability of the ZnO(100) surface.

PMID- 23949187
TI  - Genetic testing for inherited eye disease: who benefits?

PMID- 23949188
TI  - A simplified and structured teaching tool for the evaluation and management of
      pulseless electrical activity.
AB  - Cardiac arrest victims who present with pulseless electrical activity (PEA)
      usually have a grave prognosis. Several conditions, however, have cause-specific
      treatments which, if applied immediately, can lead to quick and sustained
      recovery. Current teaching focuses on recollection of numerous conditions that
      start with the letters H or T as potential causes of PEA. This teaching method is
      too complex, difficult to recall during resuscitation, and does not provide
      guidance to the most effective initial interventions. This review proposes a
      structured algorithm that is based on the differentiation of the PEA rhythm into
      narrow- or wide-complex subcategories, which simplifies the working differential
      and initial treatment approach. This, in conjunction with bedside ultrasound, can
      quickly point towards the most likely cause of PEA and thus guide resuscitation.

PMID- 23949189
TI  - Broncholithiasis with recurrent lithoptysis: a case report.
AB  - OBJECTIVE: To report a case of broncholithiasis with different types of calculi
      in the tracheobronchial tree. CLINICAL PRESENTATION AND INTERVENTION: A 50-year
      old male who suffered from hemoptysis presented with recurrent broncholith
      expectoration due to past tuberculous middle lobe syndrome. Bronchoscopic
      examination revealed loose and embedded broncholiths located at two different
      bronchi. A surgical resection was suggested, but he refused. CONCLUSION: The
      diagnosis of broncholithiasis should be kept in mind in patients who had
      hemoptysis and calcified mediastinal lymph nodes on thorax computerized
      tomography, and diagnostic bronchoscopy should be done to prove the relationship
      of the tracheobronchial tree with a broncholith.

PMID- 23949190
TI  - [Treatment of phalangeal fractures using the mini-hook plate. An alternative for
      surgical fixation of small phalangeal bone fragments?].
AB  - BACKGROUND: Fixation of the small bony fragments of the phalanges is often
      difficult. In this study a clinical and radiological evaluation was carried out
      after operative treatment using the mini-hook plate. PATIENTS AND METHODS:
      Between 2003 and 2006 a total of 36 fractures were treated operatively using the
      mini-hook plate. Of the patients 24 had an basal avulsion fracture of the distal
      phalanx and 11 patients (12 fractures) had other bony avulsion fractures of the
      phalanges. The patients were evaluated clinically and radiologically as well as
      using the disabilities of the arm, shoulder and hand (DASH) questionnaire.
      RESULTS: A total of 29 patients with 30 fractures were examined. The mean follow
      up was 13.6 months. The mean range of motion in the affected finger joint was
      60.3  degrees  and the mean DASH score was 2.8 points. Postoperatively five nail
      growth defects, one infection and one secondary dislocation of the implant were
      observed. CONCLUSION: Using the mini-hook plate, preservation of the joint and
      stable internal fixation with no need for temporary arthrodesis is possible;
      however, prerequisites are experience and skill of the surgeon with a difficult
      surgical technique.

PMID- 23949191
TI  - [Abduction/external rotation immobilization after primary traumatic anterior
      shoulder dislocation: which ortheses are suitable?].
AB  - BACKGROUND: Immobilization of the shoulder in 60  degrees  external rotation and
      30  degrees  abduction after primary anterior shoulder dislocation has been shown
      to allow anatomical reduction and potential healing of the capsule-labrum
      complex. The purpose of the present study was to evaluate commercially available
      shoulder braces concerning functionality and comfort as well as for potential
      problems. METHODS: In this study ten healthy subjects (6 female, 4 male and
      average age 23 years) tested four braces: 1. Omo Immobil (Ottobock), 2. Quadrat
      (DJO Global), 3. MP Airplane Axilla (Horst Rattenhuber GmbH) and 4. ARC XR
      (Bledsoe Brace Systems) with respect to functionality and comfort. Each subject
      completed simulated activities of daily living (ADLs) and a the end of each ADL
      the subject evaluated comfort, difficulty of the activities and potential pain on
      a points scale. The position or the change of the position were controlled by
      digital photographs. Additionally it was checked whether the subjects could
      actively change the position of the brace contrary to the desired position.
      RESULTS: Braces 3 and 4 were rated significantly more comfortable (p < 0.05).
      Even the difficulty of the activities was rated lower and in particular putting
      on and taking off the braces was assessed to be significantly easier in
      comparison to braces 1 and 2. In addition, differences of potential pain were
      statistically significant and pain was experienced only with braces 1 and 2. The
      measuring of the position showed no significant differences (p > 0.05). For
      braces 1 and 2 the active change of the position by subjects was significantly
      higher and the arm could be rotated more against the favored position (p < 0.05).
      Between braces 3 and 4, there were no statistical differences during the whole
      evaluation. CONCLUSIONS: Ortheses where the main joint is positioned in and not
      in front of the axilla or which can ensure a jointless stabilization of the
      shoulder or which allow an improved position by an additional sling on the
      opposite shoulder, are most qualified for immobilization of the shoulder in an
      external rotation/abduction position with respect to functionality and comfort.

PMID- 23949192
TI  - [Osteoid osteoma of the talus: a rare cause for pain in the ankle joint].
AB  - Osteoid osteomas are typically located in the femur and tibia and are mostly easy
      to diagnose based on patient age, the clinical signs and plain radiographs. In
      contrast, the diagnosis of osteoid osteomas of the foot is often delayed because
      of the atypical presentation. We report the case of a 24-year-old patient with
      persisting pain in the ankle joint over 8 years due to an osteoid osteoma of the
      talus neck.

PMID- 23949193
TI  - [Foreign body retained within ulnar nerve in the distal humerus].
AB  - This report describes the procedures applied to remove a metal foreign body
      retained inside the ulnar nerve in the distal humerus of a 49-year-old patient.
      Exemplified by an unfavorable primary treatment this article presents the first
      description of removal of an foreign body retained within a nerve whereby
      emphasis is placed on the problems associated with the preoperative and
      intraoperative localization of the foreign particle. 

PMID- 23949194
TI  - [Penetrating neck injury of a blacksmith by splitter projectile].
AB  - Laryngeal injuries are rare but potentially life-threatening injuries. Due to the
      topography of the neck, accompanying injuries of the greater blood vessels,
      cervical nerves, thoracic organs and spinal cord are common. Therefore in initial
      diagnostics, these must be excluded from injuries which determine the prognosis.
      A patient presented with ventral perforation of the larynx, initial dyspnea,
      hematemesis and left-sided emphysema of the neck. Cause of the findings, we
      treated the patient non-operatively in interdisciplinary consensus. 

PMID- 23949195
TI  - [CT-based classification aid for acetabular fractures: evaluation and clinical
      testing].
AB  - BACKGROUND: The basis for the classification of acetabular fractures depends on
      accurate radiological diagnostics. The use of conventional X-rays alone
      implicates a low intrapersonal reproducibility and interpersonal reliability. By
      applying computed tomography (CT) at an early stage in the emergency room, the
      typical diagonal X-rays of ala and obturator, on which the classification is
      based, are no longer recommended. The aim of this study was to develop a new
      reliable classification system based on standardized CT slices according to the
      system of Judet and Letournel without using diagonal X-rays. MATERIALS AND
      METHODS: In this study 12 select cases with acetabular fractures were peer
      reviewed. In each case eight characteristic CT slices (five axial, two coronal
      and one sagittal) were selected as well as the conventional anteroposterior X-ray
      of the pelvis. All cases were peer reviewed by 14 members of the "AG Becken"
      (working group pelvis). The classification of the acetabular fractures was based
      on Judet and Letournel and the results were compared with the reference
      classification. The results were scaled according to differences to the original
      classification and the relevance to the approach as well as the medical
      qualification of the member. RESULTS: A total of 167 out of 168 possible
      classifications were conducted, 90 cases (54 %) were in accordance with the
      reference classification. In 69 cases (41 %) the outcome was different, which
      would have had no influence on the choice of the surgical approach. A wrong
      classification was present eight times (5 %). According to the medical
      qualification status the senior physicians were right in 54%, the residents in 53
      %. Within the group of senior physicians 7.5 % of the classifications were
      completely wrong and 93 % of the participating members would have preferred to
      have more CT slices. CONCLUSION: The CT-based classification developed represents
      an adaption to the current standard of diagnostics of acetabular fractures and
      represents a step towards simplification of the classification. It is suitable to
      estimate the correct surgical approach and the behavior of the fracture. For an
      accurate classification and the association to one of the fracture types in the
      system of Judet and Letournel more slices and 3D reconstructions (MPR) are
      necessary.

PMID- 23949196
TI  - [LiLa classification for paediatric long bone fractures. Intraobserver and
      interobserver reliability].
AB  - BACKGROUND: There are two child-specific fracture classification systems for long
      bone fractures: the AO classification of pediatric long-bone fractures (PCCF) and
      the LiLa classification of pediatric fractures of long bones (LiLa
      classification). Both are still not widely established in comparison to the adult
      AO classification for long bone fractures. METHODS: During a period of 12 months
      all long bone fractures in children were documented and classified according to
      the LiLa classification by experts and non-experts. Intraobserver and
      interobserver reliability were calculated according to Cohen (kappa). RESULTS: A
      total of 408 fractures were classified. The intraobserver reliability for
      location in the skeletal and bone segment showed an almost perfect agreement (K =
      0.91-0.95) and also the morphology (joint/shaft fracture) (K = 0.87-0.93). Due to
      different judgment of the fracture displacement in the second classification
      round, the intraobserver reliability of the whole classification revealed
      moderate agreement (K = 0.53-0.58). Interobserver reliability showed moderate
      agreement (K = 0.55) often due to the low quality of the X-rays. Further
      differences occurred due to difficulties in assigning the precise transition from
      metaphysis to diaphysis. CONCLUSIONS: The LiLa classification is suitable and in
      most cases user-friendly for classifying long bone fractures in children.
      Reliability is higher than in established fracture specific classifications and
      comparable to the AO classification of pediatric long bone fractures. Some
      mistakes were due to a low quality of the X-rays and some due to difficulties to
      classify the fractures themselves. Improvements include a more precise definition
      of the metaphysis and the kind of displacement. Overall the LiLa classification
      should still be considered as an alternative for classifying pediatric long bone
      fractures.

PMID- 23949197
TI  - Possible role of oxidative stress and brain derived neurotrophic factor in
      triazophos induced cognitive impairment in rats.
AB  - Triazophos, O,O-diethyl-1-H-1,2,4-triazol-3-yl phosphorothioate, (TZ) is an
      organophosphate pesticide widely used as an insecticide in agriculture fields,
      however, its adverse effects on cognitive function remain unknown till date. The
      present study was designed to identify the effect of TZ on cognitive function in
      order to gain an insight into the molecular mechanism(s) probably involved in TZ
      induced toxicity. Wistar male albino rats were orally administered with TZ at 8.2
      mg/kg bw daily for 30 days. Cognitive function was assessed by evaluating step
      down latency (SDL) in passive avoidance apparatus, transfer latency (TL) on
      elevated plus maze and escape latency (EL) using morris water maze. The
      biochemical changes, in terms of malondialdehyde (MDA), reduced glutathione (GSH)
      and brain derived neurotrophic factor (BDNF) levels were evaluated in hippocampi
      regions. Relative mRNA expression and protein expression of BDNF were also
      evaluated. The results demonstrated that rats treated with TZ showed
      significantly (p < 0.01) reduced SDL and prolonged TL and EL as compared to
      control group rats. Moreover, significantly low (p < 0.01) mRNA expression and
      protein levels (p < 0.001) of BDNF, increased MDA and reduced GSH levels were
      observed in TZ treated rats. The study concludes that chronic exposure to TZ
      significantly impairs the learning and memory which may be attributed to the
      significantly reduced mRNA and protein expression of BDNF in hippocampus.
      Moreover, BDNF is negatively correlated to MDA levels and positively correlated
      to GSH levels. Hence, it can be suggested that interplay between BDNF and
      oxidative stress plays an important role in mediating the toxic effects of TZ.

PMID- 23949198
TI  - Bacopa monnieri ameliorates memory deficits in olfactory bulbectomized mice:
      possible involvement of glutamatergic and cholinergic systems.
AB  - This study investigated the effects of alcoholic extract of Bacopa monnieri (L.)
      Wettst. (BM) on cognitive deficits using olfactory bulbectomized (OBX) mice and
      the underlying molecular mechanisms of its action. OBX mice were treated daily
      with BM (50 mg/kg, p.o.) or a reference drug, tacrine (2.5 mg/kg, i.p.), 1 week
      before and continuously 3 days after OBX. Cognitive performance of the animals
      was analyzed by the novel object recognition test, modified Y maze test, and fear
      conditioning test. Brain tissues of OBX animals were used for neurochemical and
      immunohistochemical studies. OBX impaired non-spatial short-term memory, spatial
      working memory, and long-term fair memory. BM administration ameliorated these
      memory disturbances. The effect of BM on short-term memory deficits was abolished
      by a muscarinic receptor antagonist, scopolamine. OBX downregulated
      phosphorylation of synaptic plasticity-related signaling proteins: NR1 subunit of
      N-methyl-D-aspartate receptor, glutamate receptor 1 (GluR1), and calmodulin
      dependent kinase II but not cyclic AMP-responsive element binding protein (CREB),
      and reduced brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. OBX
      also reduced choline acetyltransferase in the hippocampus and cholinergic neurons
      in the medial septum, and enlarged the size of lateral ventricle. BM
      administration reversed these OBX-induced neurochemical and histological
      alterations, except the decrease of GluR1 phosphorylation, and enhanced CREB
      phosphorylation. Moreover, BM treatment inhibited ex vivo activity of
      acetylcholinesterase in the brain. These results indicate that BM treatment
      ameliorates OBX-induced cognition dysfunction via a mechanism involving
      enhancement of synaptic plasticity-related signaling and BDNF transcription and
      protection of cholinergic systems from OBX-induced neuronal damage.

PMID- 23949199
TI  - [MALDI-TOF imaging].

PMID- 23949200
TI  - A square peg in a round hole? Challenges with DALY-based "burden of disease"
      calculations in surgery and a call for alternative metrics.
AB  - INTRODUCTION: In recent years, surgical providers and advocates have engaged in a
      growing effort to establish metrics to estimate capacity for surgical services as
      well the burden of surgical diseases in resource-limited settings. The burden of
      disease (BoD) studies have established the disability-adjusted life year (DALY)
      as the primary metric to measure both disability and premature mortality.
      Nonetheless, DALY-based approaches present methodological challenges, some of
      which are unique to surgical conditions, not fully addressed through the multiple
      iterations of the BoD studies, including the most recent study. METHODS AND
      RESULTS: This paper examines these challenges in detail, including issues around
      age-weighting and discounting, and estimates of disability-weights for specific
      conditions. Surgical burden measurements of specific conditions, or through the
      assessment of hospital wards as platforms for service delivery, still have
      unresolved methodological hurdles. The 2010 BoD study addresses some of these
      issues, but many questions still remain. Other methods estimating surgical
      prevalence, backlogs in treatment, and disability incurred by delays in care may
      provide more practical approaches to disease burden that can be useful tools for
      clinicians and health advocates. CONCLUSIONS: These approaches warrant further
      exploration in LMICs and these debates require active engagement by surgical
      providers and advocates globally.

PMID- 23949201
TI  - Dietary aflatoxin B1 intake, genetic polymorphisms of CYP1A2, CYP2E1, EPHX1,
      GSTM1, and GSTT1, and gastric cancer risk in Korean.
AB  - PURPOSE: We investigated the effects of aflatoxin B1 (AFB1) intake, genetic
      polymorphisms of AFB1 metabolic enzymes, and interactions between the
      polymorphisms and intake of AFB1 with regard to the risk of gastric cancer in
      Korean. METHODS: The participants in the study included 477 gastric cancer
      patients and 477 age- and sex-matched control subjects. Direct interviews and a
      structured questionnaire were used to determine the level of exposure to AFB1,
      and the GoldenGate assay and multiplex polymerase chain reaction were used for
      genotypic analyses of the cytochrome P450 1A2 (CYP1A2), cytochrome P450 1E1,
      epoxide hydrolase 1, and glutathione S-transferase genes. RESULTS: The probable
      daily intake of AFB1 was significantly higher among gastric cancer patients than
      among control subjects (cases vs. controls: 1.91 +/- 0.87 vs. 1.65 +/- 0.72 ng/kg
      bw/day, p < 0.0001), and increased AFB1 intake was significantly associated with
      an elevated risk of gastric cancer (odds ratio 1.94; 95 % confidence interval
      1.43-2.63). However, genetic polymorphisms of AFB1 metabolic enzymes were not
      associated with gastric cancer, with the exception of CYP1A2. Moreover, there was
      no interaction between AFB1 intake and the genotypes of metabolic enzymes that
      affect gastric cancer risk. CONCLUSIONS: Our results suggest that dietary AFB1
      exposure might be associated with a risk of gastric cancer. However, the effect
      of AFB1 on gastric carcinogenesis may not be modulated by genetic polymorphisms
      of AFB1 metabolic enzymes.

PMID- 23949204
TI  - Discriminative stimulus effects of pregnanolone in rhesus monkeys.
AB  - RATIONALE: Neuroactive steroids and benzodiazepines can positively modulate GABA
      by acting at distinct binding sites on synaptic GABA(A) receptors. Although these
      receptors are thought to mediate the behavioral effects of both benzodiazepines
      and neuroactive steroids, other receptors (e.g., extrasynaptic GABA(A), N-methyl
      D-aspartate (NMDA), sigma1, or 5-HT3 receptors) might contribute to the effects
      of neuroactive steroids, accounting for differences among positive modulators.
      OBJECTIVE: The current study established the neuroactive steroid pregnanolone as
      a discriminative stimulus to determine whether actions in addition to positive
      modulation of synaptic GABA(A) receptors might contribute to its discriminative
      stimulus effects. METHODS: Four rhesus monkeys discriminated 5.6 mg/kg
      pregnanolone while responding under a fixed-ratio 10 schedule of stimulus-shock
      termination. RESULTS: Positive modulators acting at benzodiazepine, barbiturate,
      or neuroactive steroid sites produced >=80 % pregnanolone-lever responding,
      whereas drugs acting primarily at receptors other than synaptic GABA(A)
      receptors, such as extrasynaptic GABA(A), NMDA, sigma1, and 5-HT3 receptors,
      produced vehicle-lever responding. Flumazenil antagonized the benzodiazepines
      midazolam and flunitrazepam, with Schild analyses yielding slopes that did not
      deviate from unity and pA2 values of 7.39 and 7.32, respectively. Flumazenil did
      not alter the discriminative stimulus effects of pregnanolone. CONCLUSION: While
      these results do not exclude the possibility that pregnanolone acts at receptors
      other than synaptic GABA(A) receptors, they indicate a primary and possibly
      exclusive role of synaptic GABA(A) receptors in its discriminative stimulus
      effects. Reported differences in the effects of benzodiazepines and neuroactive
      steroids are not due to differences in their actions at synaptic GABA(A)
      receptors.

PMID- 23949205
TI  - fMRI response during figural memory task performance in college drinkers.
AB  - RATIONALE: Eighteen- to twenty-five-year-olds show the highest rates of alcohol
      use disorders (AUD) and heavy drinking, which may have critical neurocognitive
      implications. Regions subserving memory may be particularly susceptible to
      alcohol-related impairments. OBJECTIVE: We used blood oxygen level-dependent
      (BOLD) functional magnetic resonance imaging (fMRI) to examine the neural
      correlates of visual encoding and recognition among heavy-drinking college
      students. We predicted that heavy drinkers would show worse memory performance,
      increased frontal/parietal activation, and decreased hippocampal response during
      encoding. METHODS: Participants were 23 heavy drinkers and 33 demographically
      matched light drinkers, aged 18-20, characterized using quantity/frequency of
      drinking and AUD diagnosis. Participants performed a figural encoding and
      recognition task during fMRI. BOLD response during encoding was modeled based on
      whether each stimulus was subsequently recognized or forgotten (i.e., correct vs.
      incorrect encoding). RESULTS: There were no group differences in behavioral
      performance. Compared to light drinkers, heavy drinkers showed (1) greater BOLD
      response during correct encoding in the right hippocampus/medial temporal, right
      dorsolateral prefrontal, left inferior frontal, and bilateral posterior parietal
      cortices; (2) less left inferior frontal activation and greater bilateral
      precuneus deactivation during incorrect encoding; and (3) less bilateral insula
      response during correct recognition (clusters >10,233 MUl, p < 0.05 whole brain).
      CONCLUSIONS: This is the first investigation of the neural substrates of figural
      memory among heavy-drinking older adolescents. Heavy drinkers demonstrated
      compensatory hyperactivation of memory-related areas during correct encoding,
      greater deactivation of default mode regions during incorrect encoding, and
      reduced recognition-related response. Results could suggest use of different
      encoding and recognition strategies among heavy drinkers.

PMID- 23949206
TI  - Abuse-related and abuse-limiting effects of methcathinone and the synthetic "bath
      salts" cathinone analogs methylenedioxypyrovalerone (MDPV), methylone and
      mephedrone on intracranial self-stimulation in rats.
AB  - RATIONALE: Abuse of synthetic cathinones, popularized as "bath salts," has
      increased dramatically in the USA since their debut in 2010. Preclinical
      behavioral studies may clarify determinants of the abuse-related effects produced
      by these compounds. OBJECTIVES: This study examined behavioral effects of (+/-)
      methcathinone, (+/-)-3,4-methylenedioxypyrovalerone (MDPV), (+/-)-3,4
      methylenedioxymethcathinone (methylone), and (+/-)-4-methylmethcathinone
      (mephedrone) in rats using intracranial self-stimulation (ICSS). METHODS: Male
      Sprague-Dawley rats (n = 18) with electrodes targeting the medial forebrain
      bundle responded for multiple frequencies of brain stimulation and were tested in
      two phases. First, dose-effect curves for methcathinone (0.1-1.0 mg/kg), MDPV
      (0.32-3.2 mg/kg), methylone (1.0-10 mg/kg), and mephedrone (1.0-10 mg/kg) were
      determined. Second, time courses were determined for effects produced by the
      highest dose of each compound. RESULTS: Methcathinone produced dose- and time
      dependent facilitation of ICSS. MDPV, methylone, and mephedrone produced dose-
      and time-dependent increases in low rates of ICSS maintained by low brain
      stimulation frequencies, but also produced abuse-limiting depression of high ICSS
      rates maintained by high brain stimulation frequencies. Efficacies to facilitate
      ICSS were methcathinone >= MDPV >= methylone > mephedrone. Methcathinone was the
      most potent compound, and MDPV was the longest acting compound. CONCLUSIONS: All
      compounds facilitated ICSS at some doses and pretreatment times, which is
      consistent with abuse liability for each of these compounds. However, efficacies
      of compounds to facilitate ICSS varied, with methcathinone displaying the highest
      efficacy and mephedrone displaying the lowest efficacy to facilitate ICSS.

PMID- 23949207
TI  - Altered magnetic resonance images of brain and social behaviors of hatchling, and
      expression of thyroid hormone receptor betamRNA in cerebellum of embryos after
      Methimazole administration.
AB  - RATIONALE AND OBJECTIVES: The effects of low thyroid hormone level during
      embryogenesis on MRI of the brain and social behaviors of hatchlings were
      examined using "fertilized hen's egg-embryo-chick" system. METHODS AND RESULTS:
      Control and hatchlings treated with methimazole (20 MUmol/egg), which hatched 3
      days later than controls were examined. The results are as follows: 1. The MRI
      examination of the midsagittal section of the brain on hatch day showed that the
      sizes, by T1- and ADC values by diffusion-weighted images, of the optic lobe and
      cerebellum of the MMI-hatchlings were significantly bigger than those of the
      controls. 2. The social behaviors on post-hatch day 3 were based on the following
      tests: (a) Aggregation test: The speed of four chicks, individually isolated by
      cardboard barriers in a box, to make a group upon the removal of barriers. (b)
      Belongingness tests: The speed of a chick isolated at a corner to join the group
      of three chicks placed at the opposite corner. (c) Vocalization test: The number
      of decibel produced by a chick isolated at a corner using a sound meter. These
      tests demonstrated that MMI-hatchlings took longer times and had weaker
      vocalization than the controls, significantly. 3. Upregulation of THRbeta mRNA
      after MMI treatment suggested that THR was necessary for cerebellum development.
      CONCLUSIONS: The MMI exposure during the last week of embryogenesis possibly
      delayed the myelination of certain brain regions and impaired the social
      behaviors of hatchlings. The chick embryos can be easily induced with
      hypothyroidism without maternal influences, and the hatchling's behaviors were
      analyzed using a video camera. The present method will be useful for assessing
      the effects of unfavorable influences during embryogenesis on social behaviors in
      later life.

PMID- 23949208
TI  - Oral supplementation of specific collagen peptides has beneficial effects on
      human skin physiology: a double-blind, placebo-controlled study.
AB  - Various dietary supplements are claimed to have cutaneous anti-aging properties;
      however, there are a limited number of research studies supporting these claims.
      The objective of this research was to study the effectiveness of collagen
      hydrolysate (CH) composed of specific collagen peptides on skin biophysical
      parameters related to cutaneous aging. In this double-blind, placebo-controlled
      trial, 69 women aged 35-55 years were randomized to receive 2.5 g or 5.0 g of CH
      or placebo once daily for 8 weeks, with 23 subjects being allocated to each
      treatment group. Skin elasticity, skin moisture, transepidermal water loss and
      skin roughness were objectively measured before the first oral product
      application (t0) and after 4 (t1) and 8 weeks (t2) of regular intake. Skin
      elasticity (primary interest) was also assessed at follow-up 4 weeks after the
      last intake of CH (t3, 4-week regression phase). At the end of the study, skin
      elasticity in both CH dosage groups showed a statistically significant
      improvement in comparison to placebo. After 4 weeks of follow-up treatment, a
      statistically significantly higher skin elasticity level was determined in
      elderly women. With regard to skin moisture and skin evaporation, a positive
      influence of CH treatment could be observed in a subgroup analysis, but data
      failed to reach a level of statistical significance. No side effects were noted
      throughout the study.

PMID- 23949209
TI  - Unusual formation of thiaisoporphyrins from 21-thiaporphyrins.
AB  - We report the unusual formation of thiaisoporphyrins containing bridging
      sp(3)meso carbon between two pyrroles when 21-thiaporphyrins were reacted with
      PhBCl2 in dry toluene at reflux temperature. 

PMID- 23949210
TI  - Validation of the Addenbrooke's Cognitive Examination III in frontotemporal
      dementia and Alzheimer's disease.
AB  - BACKGROUND/AIMS: The aims of this study were to validate the newly developed
      version of the Addenbrooke's Cognitive Examination (ACE-III) against standardised
      neuropsychological tests and its predecessor (ACE-R) in early dementia. METHODS:
      A total of 61 patients with dementia (frontotemporal dementia, FTD, n = 33, and
      Alzheimer's disease, AD, n = 28) and 25 controls were included in the study.
      RESULTS: ACE-III cognitive domains correlated significantly with standardised
      neuropsychological tests used in the assessment of attention, language, verbal
      memory and visuospatial function. The ACE-III also compared very favourably with
      its predecessor, the ACE-R, with similar levels of sensitivity and specificity.
      CONCLUSION: The results of this study provide objective validation of the ACE-III
      as a screening tool for cognitive deficits in FTD and AD.

PMID- 23949211
TI  - Singlet oxygen-sensitized delayed fluorescence of common water-soluble
      photosensitizers.
AB  - Six common water-soluble singlet oxygen ((1)O2) photosensitizers - 5,10,15,20
      tetrakis(1-methyl-4-pyridinio) porphine (TMPyP), meso-tetrakis(4
      sulfonathophenyl)porphine (TPPS4), Al(III) phthalocyanine chloride tetrasulfonic
      acid (AlPcS4), eosin Y, rose bengal, and methylene blue - were investigated in
      terms of their ability to produce delayed fluorescence (DF) in solutions at room
      temperature. All the photosensitizers dissolved in air-saturated phosphate
      buffered saline (PBS, pH 7.4) exhibit easily detectable DF, which can be nearly
      completely quenched by 10 mM NaN3, a specific (1)O2 quencher. The DF kinetics has
      a biexponential rise-decay character in a microsecond time domain. Therefore, we
      propose that singlet oxygen-sensitized delayed fluorescence (SOSDF), where the
      triplet state of a photosensitizer reacts with (1)O2 giving rise to an excited
      singlet state of the photosensitizer, is the prevailing mechanism. It was
      confirmed by additional evidence, such as a monoexponential decay of triplet
      triplet transient absorption kinetics, dependence of SOSDF kinetics on oxygen
      concentration, absence of SOSDF in a nitrogen-saturated sample, or the effect of
      isotopic exchange H2O-D2O. Eosin Y and AlPcS4 show the largest SOSDF quantum
      yield among the selected photosensitizers, whereas rose bengal possesses the
      highest ratio of SOSDF intensity to prompt fluorescence intensity. The rate
      constant for the reaction of triplet state with (1)O2 giving rise to the excited
      singlet state of photosensitizer was estimated to be ~/>1 * 10(9) M(-1) s(-1).
      SOSDF kinetics contains information about both triplet and (1)O2 lifetimes and
      concentrations, which makes it a very useful alternative tool for monitoring
      photosensitizing and (1)O2 quenching processes, allowing its detection in the
      visible spectral region, utilizing the photosensitizer itself as a (1)O2 probe.
      Under our experimental conditions, SOSDF was up to three orders of magnitude more
      intense than the infrared (1)O2 phosphorescence and by far the most important
      pathway of DF. SOSDF was also detected in a suspension of 3T3 mouse fibroblast
      cells, which underlines the importance of SOSDF and its relevance for biological
      systems.

PMID- 23949212
TI  - Cytotoxic and immunomodulatory effects of polyhydroxyoctane isolated from
      Lentinus polychrous mycelia.
AB  - A polyhydroxyoctane, 6-methylheptane-1,2,3,4,5-pentaol (MHP), was first isolated
      from mycelia of the Thai edible mushroom Lentinus polychrous. MHP was evaluated
      for its cytotoxic and immunomodulatory effects in vitro. MHP was slightly
      cytotoxic to murine splenocytes but not to RAW264.7 cells or peripheral blood
      mononuclear cells. MHP decreased nitric oxide and intracellular O2 (-) production
      from lipopolysaccharide- and phorbol-12-myristate-13-acetate-activated RAW264.7
      cells at levels of 78.98 +/- 4.72 and 78.48 +/- 2.41 % of controls, respectively.
      The mRNA expression of pro-inflammatory mediators, including iNOS, TNF-alpha, IL
      1beta, IL-6, COX-1 and COX-2, were significantly suppressed by MHP. In addition,
      MHP significantly increased the proliferation of phytohemagglutinin and pokeweed
      mitogen-induced splenocytes. These results indicate that MHP is able to modulate
      inflammatory responses and the proliferation of both T- and B-lymphocyte cells,
      suggesting that MHP may be a good natural immunomodulator.

PMID- 23949213
TI  - Preimplantation genetic screening (PGS) with Comparative genomic hybridization
      (CGH) following day 3 single cell blastomere biopsy markedly improves IVF
      outcomes while lowering multiple pregnancies and miscarriages.
AB  - PURPOSE: To determine benefits of cleavage-stage preimplantation genetic
      screening (PGS) by array comparative genomic hybridization (CGH). METHODS: A
      retrospective case-control study was performed at a tertiary care university
      affiliated medical center. Implantation rate was looked at as a primary outcome.
      Secondary outcomes included clinical and ongoing pregnancy rates, as well as
      multiple pregnancy and miscarriage rates. Thirty five patients underwent 39 fresh
      cycles with PGS by aCGH and 311 similar patients underwent 394 invitro
      fertilization cycles. RESULT(S): The implantation rate in the CGH group doubled
      when compared to the control group (52.63 % vs. 19.15 %, p = < 0.001), clinical
      pregnancy rate was higher (69.23 % vs. 43.91 %, p = 0.0002), ongoing pregnancy
      rate almost doubled (61.54 % vs. 32.49 %, p = < 0.0001), multiple pregnancy rate
      decreased (8.33 % vs. 34.38 %, p = 0.0082) and miscarriage rate trended lower
      (11.11 % vs. 26.01 %, p = 0.13). CONCLUSION: Cleavage stage PGS with CGH is a
      feasible and safe option for aneuploidy screening that shows excellent outcomes
      when used in fresh cycles. This is the first report of cleavage stage PGS by CGH
      showing improved ongoing pregnancy rates.

PMID- 23949214
TI  - "Follicular HCG endometrium priming for IVF patients experiencing resisting thin
      endometrium. A proof of concept study".
AB  - PURPOSE: A thin endometrium is one of the most difficult problems encountered in
      assisted reproduction every day practice. Whether a daily dose of 150 IU HCG for
      7 days concomitant with estrogen administration in estrogen replacement cycles
      can increase the endometrial thickness and improve pregnancy outcome, was the
      objective of the current study. METHODS: Seventeen infertile patients with
      successive implantation failures and resisting thin endometrium, being recipients
      of fresh donor or frozen embryos were recruited. This was a prospective cohort,
      proof of concept study, NCT01768247. On day-8 or 9 of the estrogen
      administration, and continuing 8 mg estrogen per day, subcutaneous injections of
      150 IU HCG were initiated daily for 7 days. After a week on HCG priming, (day-14
      or 15) endometrial thickness was controlled with ultrasound, and progesterone was
      initiated. RESULTS: Mean endometrial thickness was increased from 5.2 mm to 6 mm
      (p = 0.008). 35.3 % of the patients had more than 20 % improvement of their
      endometrial thickness after HCG priming. 17 % achieved an endometrial thickness
      more than 7 mm, and 29.4 % did not improve their thickness at all. Interestingly,
      from the later two became pregnant. Overall, 41 % of them (7/17) finally
      delivered. CONCLUSIONS: One hundred fifty IU HCG endometrial priming for 7 days
      in the proliferative phase of estrogen substituted cycles for frozen embryos is
      highly promising, as not only the thickness of the endometrium improves but also
      eventually the receptivity appears normalized.

PMID- 23949215
TI  - A transferable H2O interaction potential based on a single center multipole
      expansion: SCME.
AB  - A transferable potential energy function for describing the interaction between
      water molecules is presented. The electrostatic interaction is described
      rigorously using a multipole expansion. Only one expansion center is used per
      molecule to avoid the introduction of monopoles. This single center approach
      turns out to converge and give close agreement with ab initio calculations when
      carried out up to and including the hexadecapole. Both dipole and quadrupole
      polarizability are included. All parameters in the electrostatic interaction as
      well as the dispersion interaction are taken from ab initio calculations or
      experimental measurements of a single water molecule. The repulsive part of the
      interaction is parametrized to fit ab initio calculations of small water clusters
      and experimental measurements of ice Ih. The parametrized potential function was
      then used to simulate liquid water and the results agree well with experiment,
      even better than simulations using some of the point charge potentials fitted to
      liquid water. The evaluation of the new interaction potential for condensed
      phases is fast because point charges are not present and the interaction can, to
      a good approximation, be truncated at a finite range. 

PMID- 23949216
TI  - Retinoblastoma protein regulates the crosstalk between autophagy and apoptosis,
      and favors glioblastoma resistance to etoposide.
AB  - Glioblastomas (GBMs) are devastating tumors of the central nervous system, with a
      poor prognosis of 1-year survival. This results from a high resistance of GBM
      tumor cells to current therapeutic options, including etoposide (VP-16).
      Understanding resistance mechanisms may thus open new therapeutic avenues. VP-16
      is a topoisomerase inhibitor that causes replication fork stalling and,
      ultimately, the formation of DNA double-strand breaks and apoptotic cell death.
      Autophagy has been identified as a VP-16 treatment resistance mechanism in tumor
      cells. Retinoblastoma protein (RB) is a classical tumor suppressor owing to its
      role in G1/S cell cycle checkpoint, but recent data have shown RB participation
      in many other cellular functions, including, counterintuitively, negative
      regulation of apoptosis. As GBMs usually display an amplification of the EGFR
      signaling involving the RB protein pathway, we questioned whether RB might be
      involved in mechanisms of resistance of GBM cells to VP-16. We observed that RB
      silencing increased VP-16-induced DNA double-strand breaks and p53 activation.
      Moreover, RB knockdown increased VP-16-induced apoptosis in GBM cell lines and
      cancer stem cells, the latter being now recognized essential to resistance to
      treatments and recurrence. We also showed that VP-16 treatment induced autophagy,
      and that RB silencing impaired this process by inhibiting the fusion of
      autophagosomes with lysosomes. Taken together, our data suggest that RB silencing
      causes a blockage on the VP-16-induced autophagic flux, which is followed by
      apoptosis in GBM cell lines and in cancer stem cells. Therefore, we show here,
      for the first time, that RB represents a molecular link between autophagy and
      apoptosis, and a resistance marker in GBM, a discovery with potential importance
      for anticancer treatment.

PMID- 23949217
TI  - Loss of cell adhesion molecule CHL1 improves homeostatic adaptation and survival
      in hypoxic stress.
AB  - Close homologue of L1 (CHL1) is a transmembrane cell adhesion molecule that is
      critical for brain development and for the maintenance of neural circuits in
      adults. Recent studies revealed that CHL1 has diverse roles and is involved in
      the regulation of recovery after spinal cord injury. CHL1 expression was
      downregulated in the cerebral cortex, hypothalamus, and brain stem after the
      induction of acute hypoxia (AH). In the current study, we sought to address the
      role of CHL1 in regulating homeostasis responses to hypoxia using CHL1-knockout
      (CHL1(-/-)) mice. We found that, compared with wild-type littermates, CHL1(-/-)
      mice showed a dramatically lower mortality rate and an augmented ventilatory
      response after they were subjected to AH. Immunofluorescence staining revealed
      that CHL1 was expressed in the carotid body (CB), the key oxygen sensor in
      rodents, and CHL1 expression level in the CB as assayed by western blot was
      decreased after hypoxic exposure. The number of glomus cells and the expression
      of tyrosine hydroxylase (a marker for glomus cells) in the CB of CHL1(-/-) mice
      appeared to be increased compared with CHL1(+/+) mice. In addition, in the ex
      vivo CB preparation, hypoxia induced a significantly greater afferent nerve
      discharge in CHL1(-/-) mice compared with CHL1(+/+) mice. Furthermore, the
      arterial blood pressure and plasma catecholamine levels of CHL1(-/-) mice were
      also significantly higher than those of CHL1(+/+) mice. Our findings first
      demonstrate that CHL1 is a novel intrinsic factor that is involved in CB function
      and in the ventilatory response to AH.

PMID- 23949218
TI  - Knockdown of specific host factors protects against influenza virus-induced cell
      death.
AB  - Cell death is a characteristic consequence of cellular infection by influenza
      virus. Mounting evidence indicates the critical involvement of host-mediated
      cellular death pathways in promoting efficient influenza virus replication.
      Furthermore, it appears that many signaling pathways, such as NF-kappaB, formerly
      suspected to solely promote cell survival, can also be manipulated to induce cell
      death. Current understanding of the cell death pathways involved in influenza
      virus-mediated cytopathology and in virus replication is limited. This study was
      designed to identify host genes that are required for influenza-induced cell
      death. The approach was to perform genome-wide lentiviral-mediated human gene
      silencing in A549 cells and determine which genes could be silenced to provide
      resistance to influenza-induced cell death. The assay proved to be highly
      reproducible with 138 genes being identified in independent screens. The results
      were independently validated using siRNA to each of these candidates. Graded
      protection was observed in this screen with the silencing of any of 19 genes,
      each providing > 85% protection. Three gene products, TNFSF13 (APRIL), TNFSF12
      TNFSF13 (TWE-PRIL) and USP47, were selected because of the high levels of
      protection conferred by their silencing. Protein and mRNA silencing and
      protection from influenza-induced cell death was confirmed using multiple shRNA
      clones and siRNA, indicating the specificity of the effects. USP47 knockdown
      prevented proper viral entry into the host cell, whereas TNFSF12-13/TNFSF13
      knockdown blocked a late stage in viral replication. This screening approach
      offers the means to identify a large number of potential candidates for the
      analysis of viral-induced cell death. These results may also have much broader
      applicability in defining regulatory mechanisms involved in cell survival.

PMID- 23949219
TI  - MBNL142 and MBNL143 gene isoforms, overexpressed in DM1-patient muscle, encode
      for nuclear proteins interacting with Src family kinases.
AB  - Myotonic dystrophy type-1 (DM1) is the most prevalent form of muscular dystrophy
      in adults. This disorder is an RNA-dominant disease, caused by expansion of a CTG
      repeat in the DMPK gene that leads to a misregulation in the alternative splicing
      of pre-mRNAs. The longer muscleblind-like-1 (MBNL1) transcripts containing exon 5
      and the respective protein isoforms (MBNL142-43) were found to be overexpressed
      in DM1 muscle and localized exclusively in the nuclei. In vitro assays showed
      that MBNL142-43 bind the Src-homology 3 domain of Src family kinases (SFKs) via
      their proline-rich motifs, enhancing the SFK activity. Notably, this association
      was also confirmed in DM1 muscle and myotubes. The recovery, mediated by an siRNA
      target to Ex5-MBNL142-43, succeeded in reducing the nuclear localization of both
      Lyn and MBNL142-43 proteins and in decreasing the level of tyrosine
      phosphorylated proteins. Our results suggest an additional molecular mechanism in
      the DM1 pathogenesis, based on an altered phosphotyrosine signalling pathway.

PMID- 23949220
TI  - GluR6-FasL-Trx2 mediates denitrosylation and activation of procaspase-3 in
      cerebral ischemia/reperfusion in rats.
AB  - Global cerebral ischemia/reperfusion (I/R) facilitates the activation of
      procaspase-3 and promotes apoptosis in hippocampus. But the mechanisms have
      remained uncharacterized. Protein S-nitrosylation and denitrosylation is an
      important reversible posttranslational modification, which is a common mechanism
      in signal transduction and affects numerous physiological and pathophysiological
      events. However, it is not known whether S-nitrosylation/denitrosylation
      modification of procaspase-3 serves as a component of apoptosis and cell death
      induced by cerebral I/R. Here we show that procaspase-3 is significantly
      denitrosylated and activated after I/R in rat hippocampus. NS102, a glutamate
      receptor 6 (GluR6) antagonist, can inhibit the denitrosylation of procaspase-3
      and diminish the increased Fas ligand (FasL) and thioredoxin (Trx)-2 expression
      induced by cerebral I/R. Moreover, downregulation of FasL expression by antisense
      oligodeoxynucleotides inhibits the denitrosylation and activation of procaspase
      3. Auranofin, a TrxR inhibitor or TrxR2 antisense oligodeoxynucleotide, has
      similar effects. In primary hippocampal cultures, Lentiviral-mediated knockdown
      of FasL and TrxR2 before the oxygen and glucose deprivation/reoxygenation further
      verifies that FasL and TrxR2 are involved in the denitrosylation of procaspase-3.
      In situ TUNEL staining and cresyl violet staining validate that inhibiting
      denitrosylation of procaspase-3 may exert neuroprotective effect on apoptosis and
      cell death induced by cerebral I/R in hippocampal CA1 pyramidal neurons. This is
      the first evidence that cerebral I/R mediates procaspase-3 denitrosylation and
      activation through GluR6-FasL-Trx2 pathway, which leads to neuronal apoptosis and
      cell death.

PMID- 23949221
TI  - Defining the role of the Bcl-2 family proteins in Huntington's disease.
AB  - B-cell lymphoma 2 (Bcl-2) family proteins regulate survival, mitochondria
      morphology dynamics and metabolism in many cell types including neurons.
      Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded
      CAG repeat tract in the IT15 gene that encodes for the protein huntingtin (htt).
      In vitro and in vivo models of HD and HD patients' tissues show abnormal
      mitochondrial function and increased cell death rates associated with alterations
      in Bcl-2 family protein expression and localization. This review aims to draw
      together the information related to Bcl-2 family protein alterations in HD to
      decipher their potential role in mutated htt-related cell death and mitochondrial
      dysfunction.

PMID- 23949222
TI  - KCa3.1 channels are involved in the infiltrative behavior of glioblastoma in
      vivo.
AB  - Glioblastoma multiforme (GBM) is a diffuse brain tumor characterized by high
      infiltration in the brain parenchyma rendering the tumor difficult to eradicate
      by neurosurgery. Efforts to identify molecular targets involved in the invasive
      behavior of GBM suggested ion channel inhibition as a promising therapeutic
      approach. To determine if the Ca(2+)-dependent K(+) channel KCa3.1 could
      represent a key element for GBM brain infiltration, human GL-15 cells were
      xenografted into the brain of SCID mice that were then treated with the specific
      KCa3.1 blocker TRAM-34 (1-((2-chlorophenyl) (diphenyl)methyl)-1H-pyrazole). After
      5 weeks of treatment, immunofluorescence analyses of cerebral slices revealed
      reduced tumor infiltration and astrogliosis surrounding the tumor, compared with
      untreated mice. Significant reduction of tumor infiltration was also observed in
      the brain of mice transplanted with KCa3.1-silenced GL-15 cells, indicating a
      direct effect of TRAM-34 on GBM-expressed KCa3.1 channels. As KCa3.1 channels are
      also expressed on microglia, we investigated the effects of TRAM-34 on microglia
      activation in GL-15 transplanted mice and found a reduction of CD68 staining in
      treated mice. Similar results were observed in vitro where TRAM-34 reduced both
      phagocytosis and chemotactic activity of primary microglia exposed to GBM
      conditioned medium. Taken together, these results indicate that KCa3.1 activity
      has an important role in GBM invasiveness in vivo and that its inhibition
      directly affects glioma cell migration and reduces astrocytosis and microglia
      activation in response to tumor-released factors. KCa3.1 channel inhibition
      therefore constitutes a potential novel therapeutic approach to reduce GBM
      spreading into the surrounding tissue.

PMID- 23949223
TI  - Rad54 is required for the normal development of male and female germ cells and
      contributes to the maintainance of their genome integrity after genotoxic stress.
AB  - Rad54 is an important factor in the homologous recombination pathway of DNA
      double-strand break repair. However, Rad54 knockout (KO) mice do not exhibit
      overt phenotypes at adulthood, even when exposed to radiation. In this study, we
      show that in Rad54 KO mouse the germline is actually altered. Compared with the
      wild-type (WT) animals, these mice have less premeiotic germ cells. This germ
      cell loss is found as early as in E11.5 embryos, suggesting an early failure
      during mutant primordial germ cells development. Both testicular and ovarian KO
      germ cells exhibited high radiation sensitivity leading to a long-term
      gametogenesis defect at adulthood. The KO female germline was particularly
      affected displaying decreased litter size or sterility. Spermatogenesis recovery
      after irradiation was slower and incomplete in Rad54 KO mice compared with that
      of WT mice, suggesting that loss of germ stem cell precursors is not fully
      compensated along the successive rounds of spermatogenesis. Finally,
      spermatogenesis recovery after postnatal irradiation is in part regulated by
      glial-cell-line-derived neurotrophic factor (GDNF) in KO but not in irradiated WT
      mice, suggesting that Sertoli cell GDNF production is stimulated upon substantial
      germ cell loss only. Our findings suggest that Rad54 has a key function in
      maintaining genomic integrity of the developing germ cells.

PMID- 23949229
TI  - Nanoconfinement effects on hydrated excess protons in layered materials.
AB  - Thin water layers confined between surfaces are known for their surprising
      properties. Layered minerals, such as mackinawite, are naturally occurring
      systems where water is known to intercalate. Here we report, based on ab initio
      simulations, how excess protons can be hosted by the resulting nanostructured
      water film depending on the mackinawite interlayer distance. Even extreme
      nanoconfinement due to the mackinawite sheets is shown to not affect the
      dynamical nature of the topological defect, thus not localizing the excess
      protons but rather conserving the efficient structural (Grotthuss) diffusion
      process known in bulk water. Yet, depending on the width of the slit pore, the
      defect can bridge the bilayer water structure, thus forcing the excess proton
      into the water-depleted region between the bilayers. 

PMID- 23949225
TI  - Enhancer of zeste homolog 2 activates wnt signaling through downregulating CXXC
      finger protein 4.
AB  - Through silencing tumor suppressor genes, epigenetic changes can activate
      signaling pathways important to cancer development. In this report, we found an
      epigenetic contribution to the aberrant activation of wnt signaling in human
      gastric cancer. CXXC4 (CXXC finger protein 4) was identified as a novel target of
      EZH2 (enhancer of zeste homolog 2), and EZH2 promotes the activation of wnt
      signaling by downregulating CXXC4 expression. CXXC4 inhibits the growth of
      gastric cancer cells both in vitro and in vivo through inactivating wnt
      signaling. In contrast, depletion of CXXC4 activates wnt signaling and promotes
      the anchorage-independent growth of nontumor gastric epithelial cells. CXXC4 is
      downregulated in gastric carcinoma tissues and its downregulation is associated
      with poor outcome of gastric cancer patients (hazard ratio: 5.053, P < 0.05).
      Through its binding to dishevelled (Dvl), CXXC4 stabilizes the destruction
      complex of beta-catenin to inhibit wnt signaling. Two critical amino acid
      residues in CXXC4, K161 and T162 were found to be important to its binding to Dvl
      and the growth inhibitory effect of CXXC4. In summary, EZH2 promotes the
      activation of wnt signaling in gastric carcinogenesis through the downregulation
      of CXXC4 expression. CXXC4 is a novel potential tumor suppressor directly
      regulated by EZH2, and its expression is a significant prognosis factor for
      patients with early stages of gastric cancer.

PMID- 23949230
TI  - Diet: the "keys" to longevity.

PMID- 23949224
TI  - AP4 directly downregulates p16 and p21 to suppress senescence and mediate
      transformation.
AB  - Here we analyzed the function of the c-MYC-inducible basic helix-loop-helix
      leucine-zipper transcription factor AP4 in AP4-deficient mouse embryo fibroblasts
      (MEFs). Loss of AP4 resulted in premature senescence and resistance towards
      immortalization. Senescence was accompanied by induction of the cyclin-dependent
      kinase inhibitor-encoding genes p16, a known tumor suppressor, and p21, a
      previously described target for repression by AP4. Notably, AP4 directly
      repressed p16 expression via conserved E-box motifs in MEFs and human diploid
      fibroblasts. Senescence caused by AP4-deficiency was prevented by depletion of
      p16 and/or p21, demonstrating that these factors mediate senescence caused by AP4
      loss. As senescence induced by the loss of AP4 was rescued by ectopic AP4,
      secondary lesions were not involved in causing premature senescence. Activation
      of c-MYC resulted in repression of p21 and p16 in AP4(+/+), but not in AP4(-/-)
      MEFs. Furthermore, after combined expression of c-MYC and mutant RAS in MEFs, AP4
      was required for colony formation, anchorage-independent growth and tumor
      formation in mice. In addition, combined ectopic expression of AP4 and mutant RAS
      in MEFs resulted in colony formation. However, additional loss of the p53 tumor
      suppressor was necessary for anchorage-independent growth and tumor formation of
      MEFs by combined AP4 and mutant RAS expression. In conclusion, this study
      identified AP4 as an oncogenic antagonist of cellular senescence. AP4 achieves
      this effect by direct repression of p16 and p21, and may thereby critically
      contribute to c-MYC function and tumor progression.

PMID- 23949231
TI  - Peritonitis in the patient on peritoneal dialysis: does the composition of the
      dialysis fluid make a difference?

PMID- 23949233
TI  - AKI is around the world but public recognition is lacking.

PMID- 23949232
TI  - Association of biocompatible peritoneal dialysis solutions with peritonitis risk,
      treatment, and outcomes.
AB  - BACKGROUND AND OBJECTIVES: The effect of biocompatible peritoneal dialysis (PD)
      solutions on PD-related peritonitis is unclear. This study sought to evaluate the
      relationship between use of biocompatible solutions and the probability of
      occurrence or clinical outcomes of peritonitis. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: The study included all incident Australian patients receiving PD
      between January 1, 2007, and December 31, 2010, using Australia and New Zealand
      Dialysis and Transplant Registry data. All multicompartment PD solutions of
      neutral pH were categorized as biocompatible solutions. The independent
      predictors of peritonitis and the use of biocompatible solutions were determined
      by multivariable, multilevel mixed-effects Poisson and logistic regression
      analysis, respectively. Sensitivity analyses, including propensity score
      matching, were performed. RESULTS: Use of biocompatible solutions gradually
      declined (from 7.5% in 2007 to 4.2% in 2010), with preferential use among smaller
      units and among younger patients without diabetes mellitus. Treatment with
      biocompatible solution was associated with significantly greater overall rate of
      peritonitis (0.67 versus 0.47 episode per patient-year; incidence rate ratio,
      1.49; 95% confidence interval [CI], 1.19 to 1.89) and with shorter time to first
      peritonitis (hazard ratio [HR], 1.48; 95% CI, 1.17 to 1.87), a finding replicated
      in propensity score-matched cohorts (HR, 1.36; 95% CI, 1.09 to 1.71).
      CONCLUSIONS: In an observational registry study, use of biocompatible PD
      solutions was associated with higher overall peritonitis rates and shorter time
      to first peritonitis. Further randomized studies adequately powered for a primary
      peritonitis outcome are warranted.

PMID- 23949234
TI  - Time to improve fluid management in hemodialysis: should we abandon clinical
      assessment and routinely use bioimpedance?

PMID- 23949235
TI  - Bioimpedance-guided fluid management in hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Achieving and maintaining optimal fluid status remains
      a major challenge in hemodialysis therapy. The aim of this interventional study
      was to assess the feasibility and clinical consequences of active fluid
      management guided by bioimpedance spectroscopy in chronic hemodialysis patients.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Fluid status was optimized
      prospectively in 55 chronic hemodialysis patients over 3 months (November 2011 to
      February 2012). Predialysis fluid overload was measured weekly using the
      Fresenius Body Composition Monitor. Time-averaged fluid overload was calculated
      as the average between pre- and postdialysis fluid overload. The study aimed to
      bring the time-averaged fluid overload of all patients into a target range of 0.5
      +/- 0.75 L within the first month and maintain optimal fluid status until study
      end. Postweight was adjusted weekly according to a predefined protocol. RESULTS:
      Time-averaged fluid overload in the complete study cohort was 0.9 +/- 1.6 L at
      baseline and 0.6 +/- 1.1 L at study end. Time-averaged fluid overload decreased
      by -1.20 +/- 1.32 L (P<0.01) in the fluid-overloaded group (n=17), remained
      unchanged in the normovolemic group (n=26, P=0.59), and increased by 0.59 +/-
      0.76 L (P=0.02) in the dehydrated group (n=12). Every 1 L change in fluid
      overload was accompanied by a 9.9 mmHg/L change in predialysis systolic BP
      (r=0.55, P<0.001). At study end, 76% of all patients were either on time-averaged
      fluid overload target or at least closer to target than at study start. The
      number of intradialytic symptoms did not change significantly in any of the
      subgroups. CONCLUSIONS: Active fluid management guided by bioimpedance
      spectroscopy was associated with an improvement in overall fluid status and BP.

PMID- 23949236
TI  - Acute posterior multifocal placoid pigment epitheliopathy as a choroidopathy:
      what we learned from adaptive optics imaging.

PMID- 23949237
TI  - Aquaporin-1 is associated with arterial capillary proliferation and hepatic
      sinusoidal transformation contributing to portal hypertension in primary biliary
      cirrhosis.
AB  - Although aquaporins (AQPs) in normal hepatobiliary system have been studied,
      little is known about AQP localization and changes in the hepatic microvascular
      system including sinusoids in cholestatic liver. The present study aimed to
      clarify the localization of AQP-1 in the microvessels in normal human liver and
      in primary biliary cirrhosis (PBC). Human normal liver (control) and PBC liver
      specimens were obtained. Immunohistochemistry, Western blotting, in situ
      hybridization (ISH) and electron microscopic examination for AQP-1 were
      conducted. In control liver and stages I-II PBC liver, AQP-1 immunoreactivity was
      mainly localized in portal venules, hepatic arterioles and bile ducts in the
      portal tract, but was hardly detected in the sinusoids. However, AQP-1 expression
      was enhanced in the proliferated bile ductules in PBC. In stages III-IV PBC liver
      tissues, AQP-1 was aberrantly expressed in proliferated arterial capillaries
      opening into the sinusoids at the peripheral edge of regenerating hepatic nodules
      and in the fibrotic septa. Overexpression of AQP-1 at protein and mRNA levels was
      demonstrated by Western blot and ISH, respectively. Angiogenetic and fibrotic
      responses are probably induced by AQP-1, leading to enhanced pouring of arterial
      blood into the sinusoids; thus, contributing to progression of portal
      hypertension in PBC. 

PMID- 23949238
TI  - Effectively control negative thermal expansion of single-phase ferroelectrics of
      PbTiO3-(Bi,La)FeO3 over a giant range.
AB  - Control of negative thermal expansion is a fundamentally interesting topic in the
      negative thermal expansion materials in order for the future applications.
      However, it is a challenge to control the negative thermal expansion in
      individual pure materials over a large scale. Here, we report an effective way to
      control the coefficient of thermal expansion from a giant negative to a near zero
      thermal expansion by means of adjusting the spontaneous volume
      ferroelectrostriction (SVFS) in the system of PbTiO3-(Bi,La)FeO3 ferroelectrics.
      The adjustable range of thermal expansion contains most negative thermal
      expansion materials. The abnormal property of negative or zero thermal expansion
      previously observed in ferroelectrics is well understood according to the present
      new concept of spontaneous volume ferroelectrostriction. The present studies
      could be useful to control of thermal expansion of ferroelectrics, and could be
      extended to multiferroic materials whose properties of both ferroelectricity and
      magnetism are coupled with thermal expansion. 

PMID- 23949240
TI  - Coronary sinus atresia with persistent left superior vena cava: unusual clinical
      presentation and endovascular management.
AB  - Atresia of the coronary sinus (ACS) is a rare congenital anomaly. When associated
      with persistent left superior vena cava (PLSVC), this defect could have no
      significant hemodynamic effect, and the patient might remain asymptomatic.
      However, vascular interventions might induce changes or complications that could
      show the anomaly. Appropriate management requires a good understanding of this
      condition. We present the first reported case of ACS and PLSVC occurring after
      thrombosis of the innominate vein (IV) after central venous catheter placement.
      The patient presented with atypical subacute chest pain and recurrent
      extrasystoles. Diagnosis and characterization of vascular anomalies was made by
      computed tomography phlebography, and the patient was successfully managed by
      endovascular recanalization of the IV. 

PMID- 23949239
TI  - Long-lasting impact of early life immune stress on neuroimmune functions.
AB  - Fever is one major cardinal sign of disease. It results from an intricate
      interplay between the immune system and the central nervous system. Bacterial or
      viral infections activate peripheral immune competent organs which send
      inflammatory signals to the brain and lead to an increase in body temperature.
      The increased body temperature creates a conducive environment to optimize the
      body's fight against the infection. A large body of experimental evidence
      suggests that early life bacterial or viral infections can lead to a long-lasting
      impact on this natural febrile response. The early life pathogenic encounter
      heightens the hypothalamic-pituitary-adrenal axis response, dampens the innate
      immune system, and consequently reduces the febrile response to a subsequent
      immune challenge during adulthood. This 'programming' effect operates only when
      such early life immune challenges occur during a critical window of either
      prenatal or postnatal development. In this review, the mechanisms underlying the
      long-lasting impact of perinatal immune challenge on adult fever are addressed.

PMID- 23949241
TI  - Tungiasis: a neglected epidermal parasitic skin disease of marginalized
      populations--a call for global science and policy.
AB  - Tungiasis (sand flea disease) is an ectoparasitic skin disease caused by the
      female sand flea/jigger flea (Tunga penetrans). As poverty is the major driving
      force of the disease, it can be called as a poverty-associated plague. It is one
      of the emerging neglected diseases in Latin America, Caribbean, sub-Saharan
      Africa, and India. The aim of the present scrutiny was to assess the public
      health impact of tungiasis, associated risk factors, and emerging opportunities
      to prevent and control tungiasis. Searches of PubMed, Google Scholar, and online
      search engines (Google, AOL, and Yahoo) using keywords "parasitic skin disease,"
      "tungiasis," "sand flea," " tungiasis-associated risk factors," "tungiasis
      prevention and control," and their synonyms were used as a source of references.
      Searches were made without time limitations. Of 167 potential articles identified
      by these criteria, 51 appropriate were selected for review. Tungiasis is
      widespread in the resource-constrained settings of low-income economies. In the
      tropics, it is highly prevalent among the impoverished populations, but the
      associated risk factors are often poorly identified and remain uncontrolled.
      Though it is a self-limiting disease with considerable morbidity, the parasite
      may cause subsequent secondary morbidity through life-threatening complications
      and infections like cellulitis, tetanus, and death. However, the direct and
      indirect sociocultural, economic, and health impact of tungiasis is often
      undervalued and misunderstood. A systematic assessment on disease burden is still
      dearth and deficient. Over the decades, tungiasis has been largely neglected by
      the scientific community, policy makers, and healthcare stakeholders. In the
      endemic regions, even tungiasis is not listed for the disease control priorities
      in the regional, national, and international agenda. The majority of the
      epidermal parasitic skin diseases particularly tungiasis needs a sustainable
      global scientific research and control policy. This urges intensive efforts to
      develop a road map that delivers a clear vision towards zero new infection by
      designing low-cost prevention and control strategies. Besides, there is an
      urgency to develop culturally appropriate communication techniques and workable
      collaboration on a global scale by bringing all the stakeholders of endemic
      countries. 

PMID- 23949242
TI  - Association between entomopathogenic nematodes and fungi for control of
      Rhipicephalus microplus (Acari: Ixodidae).
AB  - The aim of the study was to assess the effect of the association of
      entomopathogenic nematodes and fungi on Rhipicephalus microplus. The nematodes
      used were Heterorhabditis bacteriophora HP88 and Heterorhabditis indica LPP1 and
      the fungi were Metarhizium anisopliae IBCB 116 and Beauveria bassiana ESALQ 986.
      In the groups treated with the fungi, the females were immersed for 3 min in a
      conidial suspension, while in the groups treated with the nematodes, the ticks
      were exposed to infective juveniles. To evaluate the interaction between
      entomopathogens, the females were first immersed in a conidial suspension and
      then exposed to the nematodes. The egg mass weight and hatching percentage values
      of the groups treated with M. anisopliae IBCB 116 and B. bassiana ESALQ 986 in
      the two experiments were statistically similar (p > 0.05) to the values of the
      control group. In the groups treated only with nematodes, there was a significant
      reduction (p < 0.05) in the egg mass weight, a fact also observed for the
      hatching percentage of the group treated with H. indica LPP1. In all the groups
      treated with nematodes in association with fungi, there was a significant
      reduction (p < 0.05) in the egg mass weight and hatching percentage. The
      percentage of control of the groups treated with fungi alone varied from 31 to
      55%. In the groups treated with nematodes associated or not with fungi, the
      control percentage was always greater than 90% and reached 100% in the group
      treated with H. bacteriophora HP88 associated with the fungus M. anisopliae IBCB
      116.

PMID- 23949243
TI  - Molecular identification of four phenotypes of human Demodex mites (Acari:
      Demodicidae) based on mitochondrial 16S rDNA.
AB  - Classification of Demodex mites has long depended on hosts and morphological
      characteristics. However, the fact that two species coexist in the same host and
      phenotype is easily influenced by environment causes difficulty and indeterminacy
      in traditional classification. Genotype, which directly reflects the molecular
      structure characteristics, is relatively stable. In this study, species
      identification of four phenotypes of human Demodex mites was conducted. Mites
      were morphologically classified into four phenotypes: long- and short-bodied
      Demodex folliculorum with finger-like terminus and Demodex brevis with finger- or
      cone-like terminus. The mitochondrial 16S ribosomal DNA (rDNA) fragment of
      individual mite was amplified, cloned, sequenced, and aligned. Sequence
      divergences, genetic distances, transition/transversion rates, and phylogenetic
      trees were analyzed. The results demonstrated that the 16S rDNA sequence of three
      phenotypes with finger-like terminus was 337 bp, and that of phenotype with cone
      like terminus was 342 bp. The divergences, genetic distances, and
      transition/transversion rates among the three phenotypes with finger-like
      terminus were 0.0-2.7%, 0.000-0.029, and 5.0-7/0 (5/1-7/0), respectively,
      indicating an intraspecific variation. Yet, those between these three phenotypes
      and the one with cone-like terminus were 21.6-22.8%, 2.510-2.589, and 0.47-0.59
      (22/47-27/46), respectively, suggesting an interspecific variation. The five
      phylogenetic trees showed that the three phenotypes with finger-like terminus
      clustered into one branch, while the phenotype with cone-like terminus clustered
      into another. In conclusion, terminus is a major morphological characteristic for
      the identification of human Demodex species. The three phenotypes with finger
      like terminus belong to D. folliculorum, while the phenotype with cone-like
      terminus belongs to D. brevis. Molecular identification can verify and replenish
      morphological identification.

PMID- 23949244
TI  - Eimeria maxima: efficacy of recombinant Mycobacterium bovis BCG expressing apical
      membrane antigen1 against homologous infection.
AB  - Coccidiosis is one of the most important protozoan diseases and inflicts severe
      economic losses on the poultry industry. The aim of this study was to evaluate
      the capacity of Bacillus Calmette-Guerin (BCG) to deliver apical membrane
      antigen1 (AMA1) of Eimeria maxima to stimulate specific cellular and humoral
      immune responses in chickens. Day-old birds were immunized twice with rBCG/pMV261
      AMA1, rBCG/pMV361-AMA1, or BCG via oral, intranasal, and subcutaneous routes and
      then orally challenged with homologous E. maxima sporulated oocysts. Gain of body
      weight, fecal oocyst output, lesion scores, serum antibody responses, numbers of
      splenocyte CD4(+) and CD8(+) T cells, and gut cytokine transcript levels were
      assessed as measures of protective immunity. Challenge experiments demonstrated
      that rBCG vaccination via intranasal or subcutaneous routes could increase weight
      gain, decrease intestinal lesions, and reduce fecal oocyst shedding, and the
      subcutaneous and intranasal routes were superior to the oral route based on the
      immune effects. Furthermore, intranasal rBCG immunization could also lead to a
      significant increase in serum antibody, the percentage of CD4+ and CD8+ T
      lymphocyte cells, and the levels of IL-1beta, IFN-gamma, IL-15, and IL-10 mRNAs
      compared with the control group. These results suggested that intranasal rBCG
      immunization could induce a strong humoral and cellular response directed against
      homologous E. maxima infection. This study provides data for the use of rBCG to
      develop a prophylactic vaccine against coccidiosis. 

PMID- 23949246
TI  - Management of caesarean scar pregnancies using an intrauterine or abdominal
      approach based on the myometrial thickness between the gestational mass and the
      bladder wall.
AB  - AIM: To describe our experience with various interventions for caesarean scar
      pregnancies (CSPs) based on the myometrial thickness between the gestational mass
      and the bladder. METHODS: All patients were initially administered methotrexate.
      Then, the appropriate therapies hysteroscopy alone or combined with uterine
      artery embolization (group A) and direct laparoscopy alone or combined with
      laparoscopic uterine artery occlusion (group B) was selected based on the
      myometrial thickness between the gestational mass and the bladder. RESULTS: The
      uteri of all 53 patients with CSPs were conserved; no conversion to laparotomy or
      blood transfusion was required. Uterine rupture occurred in one case during
      surgery in group A. The operative time in group B was longer than group A (42 +/-
      18 vs. 80 +/- 33 min; p = 0.022). The two groups were also similar with respect
      to other characteristics (p > 0.05). CONCLUSION: Myometrial thickness should be
      considered during the management of CSPs. Surgical approaches in the treatment of
      CSPs using 2-mm boundaries may yield an optimal clinical outcome.

PMID- 23949245
TI  - Immunization with excreted-secreted antigens reduces tissue cyst formation in
      pigs.
AB  - It has been demonstrated that tachyzoite-pooled excreted-secreted antigens (ESAs)
      of Toxoplasma gondii are highly immunogenic and can be used in vaccine
      development. However, most of the information regarding protective immunity
      induced by immunization with ESAs is derived from studies using mouse model
      systems. These results cannot be extrapolated to pigs due to important
      differences in the susceptibility and immune response mechanisms between pigs and
      mice. We show that the immunization of pigs with ESAs emulsified in Freund's
      adjuvant induced not only a humoral immune response but also a cellular response.
      The cellular immune response was associated with the production of IFN-gamma and
      IL-4. The humoral immune response was mainly directed against the antigens with
      molecular masses between 34 and 116 kDa. After intraperitoneal challenge with
      10(7) T. gondii of the Gansu Jingtai strain (GJS) of tachyzoites, the immunized
      pigs remained clinically normal except for a brief low-grade fever (<=40.5 
      degrees C), while the control pigs developed clinical signs of toxoplasmosis
      (cough, anorexia, prostration, and high fever). At necropsy, visible lesions were
      found at multiple locations (enlarged mesenteric lymph nodes, an enlarged spleen
      with focal necrosis, and enlarged lungs with miliary or focal necrosis and off
      white lesions) in all of the control pigs but not in the pigs that had been
      immunized. We also found that immunization with ESAs reduced tissue cyst
      formation in the muscle (P < 0.01). Our data demonstrate that immunization with
      ESAs can trigger a strong immune response against T. gondii infection in pigs.

PMID- 23949247
TI  - Nuclear phenomena in low-energy nuclear reaction research.
AB  - This is a comment on Storms E (2010) Status of Cold Fusion, Naturwissenschaften
      97:861-881. This comment provides the following remarks to other nuclear
      phenomena observed in low-energy nuclear reactions aside from helium-4 make
      significant contributions to the overall energy balance; and normal hydrogen, not
      just heavy hydrogen, produces excess heat.

PMID- 23949248
TI  - Altruism during predation in an assassin bug.
AB  - Zelus annulosus is an assassin bug species mostly noted on Hirtella physophora, a
      myrmecophyte specifically associated with the ant Allomerus decemarticulatus
      known to build traps on host tree twigs to ambush insect preys. The Z. annulosus
      females lay egg clutches protected by a sticky substance. To avoid being trapped,
      the first three instars of nymphs remain grouped in a clutch beneath the leaves
      on which they hatched, yet from time to time, they climb onto the upper side to
      group ambush preys. Long-distance prey detection permits these bugs to capture
      flying or jumping insects that alight on their leaves. Like some other Zelus
      species, the sticky substance of the sundew setae on their forelegs aids in prey
      capture. Group ambushing permits early instars to capture insects that they then
      share or not depending on prey size and the hunger of the successful nymphs.
      Fourth and fifth instars, with greater needs, rather ambush solitarily on
      different host tree leaves, but attract siblings to share large preys. Communal
      feeding permits faster prey consumption, enabling small nymphs to return sooner
      to the shelter of their leaves. By improving the regularity of feeding for each
      nymph, it likely regulates nymphal development, synchronizing molting and
      subsequently limiting cannibalism.

PMID- 23949249
TI  - Bioavailability of cinnarizine in dogs: effect of SNEDDS loading level and
      correlation with cinnarizine solubilization during in vitro lipolysis.
AB  - PURPOSE: To investigate the effect of increasing the loading level of the poorly
      soluble drug cinnarizine in a self-nanoemulsifying drug delivery system (SNEDDS)
      both in vitro and in vivo. METHODS: A fixed dose of cinnarizine was administered
      orally to dogs in solution in different amounts of SNEDDS vehicle. Furthermore,
      the SNEDDSs were characterised using the dynamic in vitro lipolysis model.
      RESULTS: Statistical differences in bioavailability were not obtained between the
      different amounts of SNEDDS vehicle, in spite of differences in the tendency of
      cinnarizine to precipitate during in vitro lipolysis of the treatments. Use of
      the SNEDDS concept decreased the variation in cinnarizine exposure observed
      between dogs as compared to administering cinnarizine in an aqueous suspension.
      CONCLUSIONS: Optimization of SNEDDSs towards keeping the drug compound in
      solution upon in vitro lipolysis of the SNEDDSs may not be as important as
      previously suggested.

PMID- 23949251
TI  - Microspheres prepared with PLGA blends for delivery of dexamethasone for
      implantable medical devices.
AB  - PURPOSE: To develop and characterize microspheres using poly (lactic-co-glycolic
      acid) (PLGA) blends (PLGA5050 (25 KD) and PLGA6535 (70 KD)) for dexamethasone
      delivery to prevent foreign body response to implantable biosensors. METHODS: A
      single emulsion based oil/water solvent evaporation/extraction method was used to
      prepare microspheres. RESULTS: All the microspheres prepared exhibited the
      typical triphasic release profile, but with different initial burst release, lag
      phase and zero order release rates. The burst release was reduced when the two
      PLGA were mixed at a molecular level, whereas increase in burst release was
      observed when phase separation occurred. Microspheres prepared using PLGA blends
      had significantly shorter lag phase. The activation energy (Ea) of dexamethasone
      release from microspheres was similar to the Ea value of PLGA degradation. The
      release kinetics were significantly enhanced under accelerated conditions (45 and
      53 degrees C) without altering the release mechanism of the post-burst phase. A
      rank order correlation between accelerated and "real-time" release kinetics was
      observed. CONCLUSIONS: Polymer blends of PLGA can produce microspheres with
      reduced lag time. The accelerated release testing conditions investigated can
      discriminate the formulations and predict "real-time" release. Such accelerated
      release testing can be used as a rapid screening method to facilitate formulation
      development.

PMID- 23949250
TI  - In vivo fluorescence imaging of IgG1 aggregates after subcutaneous and
      intravenous injection in mice.
AB  - PURPOSE: To monitor the biodistribution of IgG1 aggregates upon subcutaneous (SC)
      and intravenous (IV) administration in mice and measure their propensity to
      stimulate an early immune response. METHODS: A human mAb (IgG1) was fluorescently
      labeled, aggregated by agitation stress and injected in SKH1 mice through SC and
      IV routes. The biodistribution of monomeric and aggregated formulations was
      monitored over 47 days by fluorescence imaging and the early immune response was
      measured by quantifying the level of relevant cytokines in serum using a Bio-plex
      assay. RESULTS: The aggregates remained at the SC injection site for a longer
      time than monomers but after entry into the systemic circulation disappeared
      faster than monomers. Upon IV administration, both monomers and aggregates spread
      rapidly throughout the circulation, and a strong accumulation in the liver was
      observed for both species. Subsequent removal from the circulation was faster for
      aggregates than monomers. No accumulation in lymph nodes was observed after SC or
      IV administration. Administration of monomers and aggregates induced similar
      cytokine levels, but SC injection resulted in higher cytokine levels than IV
      administration. CONCLUSION: These results show differences in biodistribution and
      residence time between IgG1 aggregates and monomers. The long residence time of
      aggregates at the SC injection site, in conjunction with elevated cytokine
      levels, may contribute to an enhanced immunogenicity risk of SC injected
      aggregates compared to that of monomers.

PMID- 23949253
TI  - Generation of 4-((trifluoromethyl)thio)-2H-benzo[e][1,2]thiazine 1,1-dioxides via
      a reaction of trifluoromethanesulfanylamide with 2-(2-alkynyl)benzenesulfonamide.
AB  - The incorporation of the (trifluoromethyl)thio group into the
      benzo[e][1,2]thiazine 1,1-dioxide scaffold via a reaction of
      trifluoromethanesulfanylamide with 2-(2-alkynyl)benzenesulfonamide is reported.
      The transformation proceeds under mild conditions to afford the 4
      ((trifluoromethyl)thio)-2H-benzo[e][1,2]thiazine 1,1-dioxides in moderate to good
      yields. 

PMID- 23949252
TI  - The microbiome and colorectal neoplasia: environmental modifiers of dysbiosis.
AB  - The etiology of colon cancer is complex, yet it is undoubtedly impacted by
      intestinal microbiota. Whether the contribution to colon carcinogenesis is
      generated through the presence of an overall dysbiosis or by specific pathogens
      is still a matter for debate. However, it is apparent that interactions between
      microbiota and the host are mediated by a variety of processes, including
      signaling cascades, the immune system, host metabolism, and regulation of gene
      transcription. To fully appreciate the role of microbiota in colon
      carcinogenesis, it will be necessary to expand efforts to define populations in
      niche environments, such as colonic crypts, explore cross talk between the host
      and the microbiota, and more completely define the metabolomic profile of the
      microbiota. These efforts must be pursued with appreciation that dietary
      substrates and other environmental modifiers mediate changes in the microbiota,
      as well as their metabolism and functional characteristics. 

PMID- 23949254
TI  - Current clinical trials with polo-like kinase 1 inhibitors in solid tumors.
AB  - Significant advances in cancer treatment have resulted from the targeted cancer
      therapy by understanding the process of malignant transformation. Polo-like
      kinase 1 (PLK1) has been investigated as a target for cancer therapy for several
      years. Recently, anticancer drug candidates targeting PLK1 have been developed.
      To investigate the significance of PLK1 inhibitors in cancer patients, the
      current clinical statuses of PLK1 inhibitors including BI 2536, volasertib, and
      GSK461364A were analyzed. Monotherapy with BI 2536, the first human study of PLK1
      inhibitors, has been terminated now, but its combinational study is still
      available in several solid tumors. The second-generation PLK1 inhibitor
      volasertib has an improved pharmacokinetic profile, safety, and efficacy, which
      is currently being developed under phase I/II. GSK461364 has shown a greater
      sensitive antitumor effect in p53-mutated cancer compared with that of p53-wild
      type cancer cells in a preclinical study. However, it has to be coadministered
      with an anticoagulator because of the high incidence of venous thrombotic emboli
      in clinical studies. PLK1 inhibitors showed a favorable pharmacokinetic profile,
      safety, and efficacy in patients with solid tumors. Further investigation with
      the use of PLK1 inhibitors in cancer patients who have mutated p53 or Ras and a
      high level of PLK1 as biomarkers is needed to consider the context and evaluation
      criteria of therapy.

PMID- 23949255
TI  - New estimates of racial/ethnic differences in life expectancy with chronic
      morbidity and functional loss: evidence from the National Health Interview
      Survey.
AB  - This study documents the mortality, chronic morbidity and physical functioning
      experiences of U.S. Hispanics, non-Hispanic whites, and non-Hispanic blacks 50
      years of age and older in the United States. Hispanics are classified by nativity
      to better assess an important source of heterogeneity in population health within
      that population. Drawing on mortality and morbidity data from the National Health
      Interview Survey, demographic models of healthy life expectancy are used to
      derive estimates of life expectancy, life expectancy with and without chronic
      morbidity conditions, and life expectancy with and without functional
      limitations. The results not only highlight the mortality advantages of foreign
      born Hispanics, but also document their health advantages in terms of morbidity
      and physical functioning beyond age 50. Nativity is a highly important factor
      differentiating the health and mortality experiences of Hispanics: U.S.-born
      Hispanics have a health profile more indicative of their minority status while
      foreign-born Hispanics have much more favorable mortality and health profiles.
      Differences in smoking across racial/ethnic/nativity groups is suggested as an
      important reason behind the apparent health advantages of foreign-born Hispanics
      relative to whites as well as relative to their U.S.-born counterparts.

PMID- 23949257
TI  - Obituary: William L. Woolverton.

PMID- 23949256
TI  - Disruption of model-based behavior and learning by cocaine self-administration in
      rats.
AB  - RATIONALE: Addiction is characterized by maladaptive decision-making, in which
      individuals seem unable to use adverse outcomes to modify their behavior. Adverse
      outcomes are often infrequent, delayed, and even rare events, especially when
      compared to the reliable rewarding drug-associated outcomes. As a result,
      recognizing and using information about their occurrence put a premium on the
      operation of so-called model-based systems of behavioral control, which allow one
      to mentally simulate outcomes of different courses of action based on knowledge
      of the underlying associative structure of the environment. This suggests that
      addiction may reflect, in part, drug-induced dysfunction in these systems. Here,
      we tested this hypothesis. OBJECTIVES: This study aimed to test whether cocaine
      causes deficits in model-based behavior and learning independent of requirements
      for response inhibition or perception of costs or punishment. METHODS: We trained
      rats to self-administer sucrose or cocaine for 2 weeks. Four weeks later, the
      rats began training on a sensory preconditioning and inferred value blocking
      task. Like devaluation, normal performance on this task requires representations
      of the underlying task structure; however, unlike devaluation, it does not
      require either response inhibition or adapting behavior to reflect aversive
      outcomes. RESULTS: Rats trained to self-administer cocaine failed to show
      conditioned responding or blocking to the preconditioned cue. These deficits were
      not observed in sucrose-trained rats nor did they reflect any changes in
      responding to cues paired directly with reward. CONCLUSIONS: These results imply
      that cocaine disrupts the operation of neural circuits that mediate model-based
      behavioral control.

PMID- 23949258
TI  - Ectoine-containing cream in the treatment of mild to moderate atopic dermatitis:
      a randomised, comparator-controlled, intra-individual double-blind, multi-center
      trial.
AB  - INTRODUCTION: The natural cyclic tetrahydropyrimidine, ectoine, is a low
      molecular, water-binding, organic osmolyte. Previously, topical application of
      ectoine to healthy human skin was shown to improve skin hydration as well as skin
      barrier function. OBJECTIVES: We therefore speculated that topical application of
      ectoine would be beneficial for patients with atopic dermatitis (AD), in which a
      genetically defined defect in skin barrier function is of major pathogenetic
      relevance. We assessed the efficacy of an ectoine-containing cream (EHK02-01) in
      the management of 65 patients with mild to moderate AD in a randomized, intra
      individual, double-blind, multi-center trial, in which the efficacy of ectoine
      was compared to a nonsteroidal anti-inflammatory cream previously found to
      primarily act on skin barrier function and therefore with a comparable mode of
      action. METHODS: Sixty-five patients with mild to moderate AD aged 18-65 years
      were enrolled. The patients applied EHK02-01 and the control cream on two
      symmetrical lesions twice daily for 28 days. At the beginning, after 7 and after
      28 days, treated skin areas were assessed by modified, objective local SCORAD
      (Scoring Atopic Dermatitis) and IGA (Investigator's Global Assessment) as well as
      the patients' judgment of efficacy and their assessment of pruritus. RESULTS:
      EHK02-01 was found to be very well tolerated. Even more important, efficacy of
      EHK02-01 treatment was equivalent to that achieved with the reference product.
      CONCLUSION: These results indicate that topical treatment with EHK02-01 may
      represent a novel option for the treatment of patients with AD.

PMID- 23949259
TI  - Application of science to medicine--the clinician-scientist.

PMID- 23949260
TI  - Diagnostic performance of short portable mental status questionnaire for
      screening dementia among patients attending cognitive assessment clinics in
      Singapore.
AB  - INTRODUCTION: The Short Portable Mental Status Questionnaire (SPMSQ) is a brief
      cognitive screening instrument, which is easy to use by a healthcare worker with
      little training. However, the validity of this instrument has not been
      established in Singapore. Thus, the primary aim of this study was to determine
      the diagnostic performance of SPMSQ for screening dementia among patients
      attending outpatient cognitive assessment clinics and to assess whether the
      appropriate cut-off score varies by patient's age and education. A secondary aim
      of the study was to map the SPMSQ scores with Mini-Mental State Examination
      (MMSE) scores. MATERIALS AND METHODS: SPMSQ and MMSE were administered by a
      trained interviewer to 127 patients visiting outpatient cognitive assessment
      clinics at the Singapore General Hospital, Changi General Hospital and Tan Tock
      Seng Hospital. The geriatricians at these clinics then diagnosed these patients
      with dementia or no dementia (reference standard). Sensitivity and specificity of
      SPMSQ with different cut-off points (number of errors) were calculated and
      compared to the reference standard using the Receiver Operator Characteristic
      (ROC) analysis. Correlation coefficient was also calculated between MMSE and
      SPMSQ scores. RESULTS: Based on the ROC analysis and a balance of sensitivity and
      specificity, the appropriate cut-off for SPMSQ was found to be 5 or more errors
      (sensitivity 78%, specificity 75%). The cut-off varied by education, but not by
      patient's age. There was a high correlation between SPMSQ and MMSE scores (r =
      0.814, P <0.0001). CONCLUSION: Despite the advantage of being a brief screening
      instrument for dementia, the use of SPMSQ is limited by its low sensitivity and
      specificity, especially among patients with less than 6 years of education.

PMID- 23949261
TI  - Factors associated with falls among community-dwelling older people in Taiwan.
AB  - INTRODUCTION: Falls are common among older people. Previous studies have shown
      that falls were multifactorial. However, data regarding community-dwelling
      Chinese population are minimal. We aimed to study factors associated with falls
      among community-dwelling older Chinese people. MATERIALS AND METHODS: We
      conducted a cross-sectional study in a community hospital in Taiwan in 2010. Our
      sample included 671 elders from the 3680 examinees of the free annual Senior
      Citizens Health Examination. Participants were interviewed with a detailed
      questionnaire, and 317 elders were further invited for serum vitamin D tests. The
      main outcome was falls in the previous 12 months. Predictor variables included
      sociodemographic characteristics, lifestyle risk factors, body stature, frailty,
      serum 25 (OH) D levels, and medications. RESULTS: The mean age of the 671
      participants was 75.7 +/- 6.4 years old, and 48.7% of which were female. Fallers
      comprised 21.0% of the study population. In multivariate models, female gender
      (adjusted odds ratio (aOR): 2.32), loss of height in adulthood (aOR: 1.52), low
      body weight (aOR: 2.69), central obesity (aOR: 1.67), frailty (aOR: 1.56),
      polypharmacy (aOR: 2.18) and hyperglycaemia (aOR: 1.56) were factors associated
      with falls. Vitamin D insufficiency (serum 25 (OH) D levels <30 ng/mL) was not
      associated with falls (OR: 0.78; 95% CI, 0.38 to 1.60) (n = 317) in this study.
      CONCLUSION: Among community-dwelling older people in Taiwan, falls were mainly
      associated with female gender, polypharmacy, frailty, reduced body height, low
      body weight or central obesity, and hyperglycaemia. In addition to other risk
      factors, body stature should be considered as a novel risk factor when screening
      elders at risk for falls.

PMID- 23949262
TI  - Borderline viability--neonatal outcomes of infants in Singapore over a period of
      18 years (1990 - 2007).
AB  - INTRODUCTION: This study assesses the trends and predictors of mortality and
      morbidity in infants of gestational age (GA) <27 weeks from 1990 to 2007.
      MATERIALS AND METHODS: This is a retrospective cross-sectional cohort study of
      infant deliveries between 1990 and 2007 in the largest perinatal centre in
      Singapore. This is a study of infants born at <27 weeks in 2 Epochs (Epoch 1
      (E1):1990 to 1998, Epoch 2 (E2):1999 to 2007) using logistic regression models to
      identify factors associated with mortality and composite morbidity. The main
      outcomes that were measured were the trends and predictors of mortality and
      morbidity. RESULTS: Four hundred and eight out of 615 (66.3%) live born infants
      at 22 to 26 weeks survived to discharge. Survival improved with increasing GA
      from 22% (13/59) at 23 weeks to 87% (192/221) at 26 weeks (P <0.01). Survival
      rates were not different between E1 and E2, (61.5% vs 68.8%). In logistic
      regression analysis, higher survival was independently associated with increasing
      GA and birthweight, while airleaks, severe intraventricular haemorrhage (IVH) and
      necrotizing enterocolitis (NEC) contributed to increased mortality. Rates of
      major neonatal morbidities were bronchopulmonary dysplasia (BPD) (45%), sepsis
      (35%), severe retinopathy of prematurity (ROP) (31%), severe IVH/ periventricular
      leucomalacie (PVL) (19%) and NEC (10%). Although composite morbidity comprising
      any of the above was not significantly different between the 2 Epochs (75% vs
      73%) a decreasing trend was seen with increasing GA (P <0.001). Composite
      morbidity/ mortality was significantly lower at 26 weeks (58%) compared to
      earlier gestations (P <0.001, OR 0.37, 95% CI, 0.28 to 0.48) and independently
      associated with decreasing GA and birth weight, male sex, hypotension, presence
      of patent ductus arteriosus (PDA) and airleaks. CONCLUSION: Increasing survival
      and decreasing composite morbidity was seen with each increasing week in
      gestation with marked improvement seen at 26 weeks. Current data enables
      perinatal care decisions and parental counselling.

PMID- 23949263
TI  - The medical, functional and social challenges faced by older adults with
      intellectual disability.
AB  - INTRODUCTION: Little is known about the sociodemographic and clinical profile of
      older adults with intellectual disabilities (ID) in Singapore. We studied the
      sociodemographic and clinical profile of older adults with ID and investigated
      factors associated with caregiver availability and identity in this population.
      MATERIALS AND METHODS: The study population involved all adults with ID aged >=40
      years receiving services from the Movement for the Intellectually Disabled of
      Singapore (MINDS), the largest such provider in Singapore. Information on
      sociodemographic and clinical profiles, functional status, and availability of
      caregivers were collected via interviewer-administered questionnaires from
      guardians of older adults with ID. Descriptive characteristics were computed and
      chi-square and logistic regression identifi ed predictors of caregiver
      availability and identity. RESULTS: Participation was 95% (227/239). There were
      differences in client age, gender, and caregiver availability between recipients
      of residential and non-residential services (all P <0.05). Common comorbidities
      included hyperlipidaemia (17.6%), hypertension (15.9%), psychiatric diagnoses
      (16.3%) and epilepsy (10.6%). The majority were fully independent in basic
      activities of daily living, but only 21.1% were fully communicative. Only a small
      minority (9.4%) were exercising regularly. The majority (73.5%) of clients had a
      primary caregiver; almost equal proportions relied on either parents or siblings.
      Older client age was associated independently with the lack of a primary
      caregiver, independent of greater functional dependence and presence of medical
      comorbidities in the client. CONCLUSION: Older adults with ID have multiple
      medical, functional, and social issues. More can be done to support the care of
      this unique group of adults with special needs.

PMID- 23949264
TI  - Challenges of respondent driven sampling to assess sexual behaviour and estimate
      the prevalence of human immunodeficiency virus (HIV) and syphilis in men who have
      sex with men (MSM) in Singapore.
AB  - There is a lack of representative samples to provide reliable and accurate
      seroprevalence of sexually transmitted infections (STIs) and human
      immunodeficiency virus (HIV) as well as behavioural information among men who
      have sex with men (MSM) in Singapore. We used respondent driven sampling (RDS) to
      recruit MSM. Participants completed a survey used by Asian Internet MSM Sex
      Survey (AIMSS) and were tested for HIV and syphilis. We compared the
      characteristics of the RDS participants with STI diagnosis against those who did
      not have any STI diagnosis in the past 6 months. We compared RDS participants
      with AIMSS participants. Of 72 MSM recruited, 1 was positive for HIV (1.3%) and 4
      (5.5%) tested positive for syphilis. Median age was 30 years and majority was
      Chinese (69.4%). RDS participants who had any STI diagnosis reported to have more
      use of recreational drugs (P = 0.006), and lower condom use (P = 0.054).
      Comparing RDS participants (n = 72) with the AIMSS participants (n = 2075), RDS
      respondents had >=1 male partner in the past 6 months (P = 0.003), more casual
      sex partners (P = 0.012) and more STI symptoms (P = 0.019). There was no
      difference in terms of HIV testing and recreational drug use. The HIV and
      syphilis seroprevalence rates from our study are similar to previous reports
      conducted in high-risk MSM. In contrast to other settings, RDS did not work well
      among MSM in Singapore. The public health implications of our study highlight the
      challenges in obtaining data for HIV surveillance in assessing prevalence and
      risk behaviours among MSM. 

PMID- 23949265
TI  - The quest for a H1N1 flu vaccine.

PMID- 23949266
TI  - Plant food and incense: the new substances of abuse.

PMID- 23949267
TI  - Henoch-Schonlein purpura associated with adult human immunodeficiency virus
      infection: case report and review of the literature.

PMID- 23949268
TI  - Hypnotherapy: a forgotten modality in managing chronic post-traumatic upper limb
      pain.

PMID- 23949269
TI  - Infantile scurvy masquerading as bone tumour.

PMID- 23949270
TI  - An under-recognized cause of polyarthritis: leprosy.

PMID- 23949271
TI  - A fluke diagnosis.

PMID- 23949273
TI  - Unplanned pregnancy in adolescents: association with family structure, employed
      mother, and female friends with health-risk habits and behaviors.
AB  - Previous publications have suggested that living in a nonintact family household
      and socializing with girlfriends who smoke or who consume alcoholic beverages
      favor the development of health-risk habits and customs in adolescents. However,
      their relationship with unplanned pregnancy in adolescents has not been
      determined. We investigated the association between family structure, employed
      mother, and female friends with health-risk habits and behaviors with unplanned
      pregnancy in adolescents (n = 3,130). After adjusting for low maternal
      educational level and low family income, logistic regression analyses showed that
      having an employed mother and socializing with girlfriends who have health-risk
      habits or behaviors, rather than living in a nonintact family household, appear
      to be the most important health-risk factors for unplanned pregnancy in
      adolescents. It is important for health-care programs for adolescents to be
      revised and for their strategies be strengthened in order to reach the objectives
      for which they were created.

PMID- 23949274
TI  - Combined direct and indirect bypass for moyamoya: quantitative assessment of
      direct bypass flow over time.
AB  - BACKGROUND: The optimal revascularization strategy for symptomatic adult moyamoya
      remains controversial. Whereas direct bypass offers immediate revascularization,
      indirect bypass can effectively induce collaterals over time. OBJECTIVE: Using
      angiography and quantitative magnetic resonance angiography, we examined the
      relative contributions of direct and indirect bypass in moyamoya patients after
      combined direct superficial temporal artery-to-middle cerebral artery (STA-MCA)
      bypass and indirect encephaloduroarteriosynangiosis (EDAS). METHODS: A
      retrospective review of moyamoya patients undergoing combined STA-MCA bypass and
      EDAS was conducted, excluding pediatric patients and hemorrhagic presentation.
      Patients with quantitative magnetic resonance angiography measurements of the
      direct bypass immediately and > 6 months postoperatively were included.
      Angiographic follow-up, when available, was used to assess EDAS collaterals at
      similar time intervals. RESULTS: Of 16 hemispheres in 13 patients, 11 (69%)
      demonstrated a significant (> 50%) decline in direct bypass flow at > 6 months
      compared with baseline, averaging a drop from 99 +/- 35 to 12 +/- 7 mL/min.
      Conversely, angiography in these hemispheres demonstrated prominent indirect
      collaterals, in concert with shrinkage of the STA graft. Decline in flow was
      apparent at a median of 9 months but was evident as early as 2 to 3 months.
      CONCLUSION: In this small cohort, a reciprocal relationship between direct STA
      bypass flow and indirect EDAS collaterals frequently occurred. This substantiates
      the notion that combined direct/indirect bypass can provide temporally
      complementary revascularization.

PMID- 23949275
TI  - Computational fluid dynamic analysis of intracranial aneurysmal bleb formation.
AB  - BACKGROUND: The management of unruptured aneurysms is controversial, with the
      decision to treat influenced by aneurysm characteristics including size and
      morphology. Aneurysmal bleb formation is thought to be associated with an
      increased risk of rupture. OBJECTIVE: To correlate computational fluid dynamic
      (CFD) indices with bleb formation. METHODS: Anatomic models were constructed from
      3-dimensional rotational angiography data in 27 patients with cerebral aneurysms
      harboring a single bleb. Additional models representing the aneurysm before bleb
      formation were constructed by digitally removing the bleb. We characterized
      hemodynamic features of models both with and without the blebs using CFDs. Flow
      structure, wall shear stress (WSS), pressure, and oscillatory shear index (OSI)
      were analyzed. RESULTS: There was a statistically significant association between
      bleb location at or adjacent to the point of maximal WSS (74%, P = .019),
      irrespective of rupture status. Aneurysmal blebs were related to the inflow or
      outflow jet in 89% of cases (P < .001), whereas 11% were unrelated. Maximal wall
      pressure and OSI were not significantly related to bleb location. The bleb region
      attained a lower WSS after its formation in 96% of cases (P < .001) and was also
      lower than the average aneurysm WSS in 86% of cases (P < .001). CONCLUSION:
      Cerebral aneurysm blebs generally form at or adjacent to the point of maximal WSS
      and are aligned with major flow structures. Wall pressure and OSI do not
      contribute to determining bleb location. The measurement of WSS using CFD models
      may potentially predict bleb formation and thus improve the assessment of rupture
      risk in unruptured aneurysms.

PMID- 23949277
TI  - Preventing and managing indoor falls with home-based technologies in mild and
      moderate Alzheimer's disease patients: pilot study in a community dwelling.
AB  - BACKGROUND: Alzheimer's disease (AD) is known to increase the risk of falls. We
      aim to determine the effectiveness of home-based technologies coupled with
      teleassistance service (HBTec-TS) in older people with AD. METHODS: A study of
      falls and the HBTec-TS system (with a light path combined with a teleassistance
      service) was conducted in the community. The 96 subjects, drawn from a random
      population of frail elderly people registered as receiving an allocation for lost
      autonomy from the county, were aged 65 or more and had mild-to-moderate AD with 1
      year of follow-up; 49 were in the intervention group and 47 in the control group.
      RESULTS: A total of 16 (32.7%) elderly people fell in the group with HBTec-TS
      versus 30 (63.8%) in the group without HBTec-TS. The use of HBTec-TS was
      significantly associated with a reduction in the number of indoor falls among
      elderly people with mild-to-moderate AD (OR = 0.37, 95% CI = 0.15-0.88, p =
      0.0245). CONCLUSION: The use of the HBTec-TS significantly reduced the incidence
      of primary indoor falling needing GP intervention or attendance at an emergency
      room among elderly people with AD and mild-to-moderate dementia.

PMID- 23949278
TI  - [Therapeutic manipulation of inflammation-promoting T cells: from suppression to
      self-control].

PMID- 23949279
TI  - [Primary and secondary neutropenia].
AB  - Severe chronic neutropenia (SCN) comprises a heterogeneous group of disorders
      with a common hematological and clinical phenotype characterized by absolute
      neutrophil counts (ANC) below 0,5 * 10(9)/l and increased risk of severe
      bacterial infections. The differentiation between primary and secondary
      neutropenia and the identification of causative gene mutations is of great
      importance for the estimation of prognosis. During childhood primary autoimmune
      neutropenia is the most frequent diagnosis, while secondary neutropenia
      predominates in adulthood. Despite the rarity, congenital, genetic neutropenias
      are of great value for research on normal and pathological hematopoiesis and have
      a fundamental impact on the current knowledge on hematopoiesis. To date mutations
      in more than 10 genes have been described which are mainly associated with an
      increased risk for leukemia.The treatment with hematopoietic growth factors has
      improved the long-term prognosis of SCN patients dramatically: Bacterial
      infections can be prevented and a normal participation in everyday life is
      possible. 

PMID- 23949281
TI  - Decreasing P-selectin and ICAM-1 via activating Akt: a possible mechanism by
      which PARG inhibits adhesion of mouse colorectal carcinoma CT26 cells to
      platelets.
AB  - Poly (ADP-ribose) glycohydrolase (PARG), which was discovered during studies on
      DNA damage study and in inflammation research, is an attractive target protein in
      current cancer research. The enzymatic hydrolysis of poly (ADP-ribose) (PAR) has
      not been clarified in the regulation of cancer. The purpose of this study was to
      understand the relationship between PARG and the adhesion of colorectal carcinoma
      CT26 cells to platelets. PARG was silenced by short hairpin RNA (shRNA)
      transfection in CT26 cells. A fluorescence method was used to identify adhesion
      of CT26 cells to platelets and the expression of poly (ADP-ribose) polymerase
      (PARP)-1, p-Akt, nuclear factor kappa-B (NF-kappaB), P-selectin and intercellular
      adhesion molecule-1 (ICAM-1) was analyzed by western blot in various treated
      groups and control groups. The results were as follows: (a) PARG silencing led to
      inhibition of adhesion of CT26 cells to platelets, whereas an inhibitor of p-Akt
      boosted adhesion of PARG-short hairpin RNA interference (shRNAi) CT26 cells to
      platelets; (b) a PARP-1 inhibitor depressed the expression of P-selectin and ICAM
      1 in CT26 cells; (c) PARG silencing increased phosphorylation of Akt and
      decreased expression of PARP-1, NF-kappaB, ICAM-1 and P-selectin in CT26 cells;
      and (d) a p-Akt inhibitor intensified expression of NF-kappaB, ICAM-1 and P
      selectin in PARG-shRNAi CT26 cells accordingly. These results showed the
      effectiveness of knockout of PARG in inhibiting adhesion of CT26 cells to
      platelets and its connection with the phosphatidylinositol 3 kinase/Akt pathway. 

PMID- 23949282
TI  - Targeted expression of human folylpolyglutamate synthase for selective
      enhancement of methotrexate chemotherapy in osteosarcoma cells.
AB  - The antifolate methotrexate (MTX) is an important chemotherapeutic agent for
      treatment of osteosarcoma. This drug is converted intracellularly into
      polyglutamate derivates by the enzyme folylpolyglutamate synthase (FPGS). MTX
      polyglutamates show an enhanced and prolonged cytotoxicity in comparison to the
      monoglutamate. In the present study, we proved the hypothesis that transfer of
      the human fpgs gene into osteosarcoma cells may augment their MTX sensitivity.
      For this purpose, we employed the human osteocalcin (OC) promoter, which had
      shown marked osteosarcoma specificity in promoter studies using different
      luciferase assays in osteosarcoma and non-osteosarcoma cell lines. A recombinant
      lentiviral vector was generated with the OC promoter driving the expression of
      fpgs and the gene for enhanced green fluorescent protein (egfp), which was linked
      to fpgs by an internal ribosomal entry site (IRES). As the vector backbone
      contained only a self-inactivating viral LTR promoter, any interference of the OC
      promoter by unspecific promoter elements was excluded. We tested the expression
      of FPGS and enhanced green fluorescent protein (EGFP) after lentiviral
      transduction in various osteosarcoma cell lines (human MG-63 cells and TM 791
      cells; rat osteosarcoma (ROS) 17/2.8 cells) and non-osteogenic tumor cell lines
      (293T human embryonic kidney cells, HeLa human cervix carcinoma cells). EGFP
      expression and MTX sensitivity were assessed in comparison with non-transduced
      controls. Whereas the OC promoter failed to enhance MTX sensitivity via FPGS
      expression in non-osteogenic tumor cell lines, the OC promoter mediated a
      markedly increased MTX cytotoxicity in all osteosarcoma cell lines after
      lentiviral transduction. The present chemotherapy-enhancing gene therapy system
      may have great potential to overcome in future MTX resistance in human
      osteosarcomas. 

PMID- 23949280
TI  - The emerging role of cardiovascular magnetic resonance in the evaluation of
      Kawasaki disease.
AB  - Kawasaki disease (KD) is a vasculitis affecting the coronary and systemic
      arteries. Myocardial inflammation is also a common finding in KD post-mortem
      evaluation during the acute phase of the disease. Coronary artery aneurysms
      (CAAs) develop in 15-25% of untreated children. Although 50-70% of CAAs resolve
      spontaneously 1-2 years after the onset of KD, the remaining unresolved CAAs can
      develop stenotic lesions at either their proximal or distal end and can develop
      thrombus formation leading to ischemia and/or infarction. Cardiovascular magnetic
      resonance (CMR) has the ability to perform non-invasive and radiation-free
      evaluation of the coronary artery lumen. Recently tissue characterization of the
      coronary vessel wall was provided by CMR. It can also image myocardial
      inflammation, ischemia and fibrosis. Therefore CMR offers important clinical
      information during the acute and chronic phase of KD. In the acute phase, it can
      identify myocardial inflammation, microvascular disease, myocardial infarction,
      deterioration of left ventricular function, changes of the coronary artery lumen
      and changes of the coronary artery vessel wall. During the chronic phase, CMR
      imaging might be of value for risk stratification and to guide treatment.

PMID- 23949284
TI  - Liquid-liquid extraction of neodymium(III) by dialkylphosphate ionic liquids from
      acidic medium: the importance of the ionic liquid cation.
AB  - The ionic liquids 1-hexyl-3-methylimidazolium bis(2-ethylhexyl)phosphate,
      [C6mim][DEHP], 1-hexyl-1-methylpyrrolidinium bis(2-ethylhexyl)phosphate,
      [C6mpyr][DEHP], and tetrabutylammonium bis(2-ethylhexyl)phosphate, [N4444][DEHP],
      were prepared and characterized using (1)H and (13)C NMR spectroscopy. The
      extraction behavior of neodymium(iii) from nitrate medium by these ionic liquids,
      diluted with the room temperature ionic liquids 1-hexyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide, [C6mim][NTf2], 1-hexyl-3-methylpyrrolidinium
      bis(trifluoromethylsulfonyl)imide, [C6mpyr][NTf2], and tributylmethylammonium
      bis(trifluoromethylsulfonyl)imide, [N1444][NTf2], was studied. The distribution
      ratio of neodymium(iii) was measured as a function of various parameters, such as
      pH, concentration of the ionic liquid extractant, nature of diluents,
      concentration of ionic liquid cations and nitrate anions in the aqueous phase.
      The extraction behavior was compared with that obtained for a solution of the
      molecular extractant bis(2-ethylhexyl)phosphoric acid (DEHPA) in an ionic liquid
      diluent. The extraction of neodymium(iii) in the ionic liquids [C6mim][DEHP] and
      [C6mpyr][DEHP] showed markedly different extraction properties in comparison with
      that of the quaternary ammonium analogue [N4444][DEHP], especially concerning the
      pH dependence of the extraction process. These results show that the extraction
      process can be tuned by the selection of the ionic liquid cation. The extraction
      experiments also included the trivalent rare-earth ions lanthanum(iii),
      cerium(iii), praseodymium(iii), ytterbium(iii) and yttrium(iii). Studies of the
      stripping behavior and the reusability of the ionic liquids were carried out,
      which indicate that the ionic liquids can be reused with no loss in activity. 

PMID- 23949285
TI  - From amoeba to macrophages: exploring the molecular mechanisms of Legionella
      pneumophila infection in both hosts.
AB  - Legionella pneumophila is a Gram-negative bacterium and the causative agent of
      Legionnaires' disease. It replicates within amoeba and infects accidentally human
      macrophages. Several similarities are seen in the L. pneumophila-infection cycle
      in both hosts, suggesting that the tools necessary for macrophage infection may
      have evolved during co-evolution of L. pneumophila and amoeba. The establishment
      of the Legionella-containing vacuole (LCV) within the host cytoplasm requires the
      remodeling of the LCV surface and the hijacking of vesicles and organelles. Then
      L. pneumophila replicates in a safe intracellular niche in amoeba and
      macrophages. In this review we will summarize the existing knowledge of the L.
      pneumophila infection cycle in both hosts at the molecular level and compare the
      factors involved within amoeba and macrophages. This knowledge will be discussed
      in the light of recent findings from the Acanthamoeba castellanii genome analyses
      suggesting the existence of a primitive immune-like system in amoeba. 

PMID- 23949283
TI  - Improved cytotoxic T-lymphocyte immune responses to a tumor antigen by vaccines
      co-expressing the SLAM-associated adaptor EAT-2.
AB  - The signaling lymphocytic activation molecule-associated adaptor Ewing's
      sarcoma's-activated transcript 2 (EAT-2) is primarily expressed in dendritic
      cells, macrophages and natural killer cells. Including EAT-2 in a vaccination
      regimen enhanced innate and adaptive immune responses toward pathogen-derived
      antigens, even in the face of pre-existing vaccine immunity. Herein, we
      investigate whether co-vaccinations with two recombinant Ad5 (rAd5) vectors, one
      expressing the carcinoembryonic antigen (CEA) and one expressing EAT-2, can
      induce more potent CEA-specific cytotoxic T lymphocyte (CTL) and antitumor
      activity in the therapeutic CEA-expressing MC-38 tumor model. Our results suggest
      that inclusion of EAT-2 significantly alters the kinetics of Th1-biasing
      proinflammatory cytokine and chemokine responses, and enhances anti-CEA-specific
      CTL responses. As a result, rAd5-EAT2-augmented rAd5-CEA vaccinations are more
      efficient in eliminating CEA-expressing target cells as measured by an in vivo
      CTL assay. Administration of rAd5-EAT2 vaccines also reduced the rate of growth
      of MC-38 tumor growth in vivo. Also, an increase in MC-38 tumor cell apoptosis
      (as measured by hematoxylin and eosin staining, active caspase-3 and granzyme B
      levels within the tumors) was observed. These data provide evidence that more
      efficient, CEA-specific effector T cells are generated by rAd5 vaccines
      expressing CEA, when augmented by rAd5 vaccines expressing EAT-2, and this
      regimen may be a promising approach for cancer immunotherapy in general. 

PMID- 23949286
TI  - Plant viral vectors for delivery by Agrobacterium.
AB  - Plant viral vectors delivered by Agrobacterium are the basis of several
      manufacturing processes that are currently in use for producing a wide range of
      proteins for multiple applications, including vaccine antigens, antibodies,
      protein nanoparticles such as virus-like particles (VLPs), and other protein and
      protein-RNA scaffolds. Viral vectors delivered by agrobacterial T-DNA transfer
      (magnifection) have also become important tools in research. In recent years,
      essential advances have been made both in the development of second-generation
      vectors designed using the 'deconstructed virus' approach, as well as in the
      development of upstream manufacturing processes that are robust and fully
      scalable. The strategy relies on Agrobacterium as a vector to deliver DNA copies
      of one or more viral RNA/DNA replicons; the bacteria are delivered into leaves by
      vacuum infiltration, and the viral machinery takes over from the point of T-DNA
      transfer to the plant cell nucleus, driving massive RNA and protein production
      and, if required, cell-to-cell spread of the replicons. Among the most often used
      viral backbones are those of the RNA viruses Tobacco mosaic virus (TMV), Potato
      virus X (PVX) and Cowpea mosaic virus (CPMV), and the DNA geminivirus Bean yellow
      dwarf virus. Prototypes of industrial processes that provide for high yield,
      rapid scale up and fast manufacturing cycles have been designed, and several GMP
      compliant and GMP-certified manufacturing facilities are in place. These efforts
      have been successful as evidenced by the fact that several antibodies and vaccine
      antigens produced by magnifection are currently in clinical development. 

PMID- 23949291
TI  - Hepatitis B and C virus infections among pregnant women in Arab and African
      countries.
AB  - INTRODUCTION: The epidemiology of viral hepatitis during pregnancy is of
      paramount importance for health planners and program managers. Data on viral
      hepatitis during pregnancy are not readily available in many African and Arab
      countries. Both regions have their own unique geography, and comprise over 59
      states with crossover and interaction of different cultures. METHODOLOGY: A
      systematic electronic search of the published literature was conducted and data
      on epidemiology and risk factors of maternal hepatitis B virus (HBV) infection
      and hepatitis C (HCV) infection in Arab and African countries were extracted from
      relevant studies. RESULTS: The serology of hepatitis viruses varies greatly among
      these countries, with different viral genotype patterns. Such a variation in
      prevalence could be explained by the different risk factors involved. Sexual
      contact, perinatal infection, blood and its derivatives, hemodialysis,
      intravenous and percutaneous drug use, and occupational, habitual, and social
      behavior have been identified as risk factors for hepatitis transmission in
      various settings in these countries. CONCLUSIONS: Infection from hepatitis B and
      C viruses imposes major socioeconomic and even political burdens on such young
      and dynamic societies. Thus strategies and clear policies of intervention are
      required to combat the consequences of hepatitis B and C at both the regional and
      national levels.

PMID- 23949287
TI  - Inhibition of Hsp90 and 70 sensitizes melanoma cells to hyperthermia using
      ferromagnetic particles with a low Curie temperature.
AB  - BACKGROUND: Heat shock protein (Hsp) 90 is a key regulator of various oncogene
      products and cell-signaling molecules, while Hsp70 protects against heat-induced
      apoptosis. We previously described a system in which hyperthermia was produced
      using thermosensitive ferromagnetic particles (FMPs) with a Curie temperature (T
      c) of 43  degrees C to mediate automatic temperature control, and demonstrated
      its antitumor effect in a mouse melanoma model. In the present study, the
      antitumor effects of combining Hsp90 inhibitor (17DMAG) and Hsp70 inhibitor
      (quercetin) with FMP-mediated hyperthermia were examined. METHODS: Expressions of
      Hsp90/70 and Akt were evaluated using Western blotting in vitro. In an in vivo
      study, melanoma cells were subcutaneously injected into the backs of C57BL/6
      mice. FMPs were then injected into the resultant tumors, and the mice were
      divided into groups treated with quercetin and/or 17DMAG with/without
      hyperthermia. When exposed to a magnetic field, the temperature of tissues
      containing FMPs increased and stabilized at the T c. The TUNEL method was used to
      determine whether hyperthermia induced apoptosis within tumors. RESULTS: In the
      group pretreated with hyperthermia + quercetin + 17DMAG, Akt expression was
      reduced in vitro, the incidence of apoptosis within tumors was greater, and tumor
      growth was significantly suppressed 20 days after FMP injection in vivo, compared
      with other treatment groups. The survival rates among tumor-bearing mice observed
      for a period of 40 days were significantly higher in the hyperthermia + quercetin
      + 17DMAG group. CONCLUSION: Combining Hsp90/70 inhibition with hyperthermia
      appears to increase their antitumor effects. Thus, the combination of FMP
      mediated, self-regulating hyperthermia with Hsp90/70 inhibition has important
      implications for cancer treatment.

PMID- 23949292
TI  - Surveillance of post-caesarean surgical site infections in a hospital with
      limited resources, Cambodia.
AB  - INTRODUCTION: In Cambodia, we implemented a pilot surveillance of superficial
      surgical site infections (SSSI) following caesarean deliveries (CD) in a
      provincial hospital, to estimate their incidence, describe their clinical
      management, and determine their causative pathogens. METHODOLOGY: Between October
      2010 and February 2011, all women admitted for CD were included in the
      surveillance. Their clinical condition was monitored for a post-operative period
      of 30 days, including two assessments performed by surgeons. Cases were
      clinically diagnosed by surgeons, with bacterial cultures performed. RESULTS: Of
      the 222 patients admitted for CD, 176 (79.3%) were monitored for 30 days. Of
      these, 11 were diagnosed with a SSSI, giving an incidence rate of 6.25% (95% CI
      3.2-10.9). Four of the cases (36.4%) were detected after hospital discharge.
      Length of hospitalization was significantly longer for the SSSI cases. All 222
      patients were prescribed antibiotics. Ampicillin was administered intravenously
      to 98.6% of them, with subsequent oral amoxicillin given to 82.9%. Three of six
      pus samples collected were positive on culture: two with Staphylococcus aureus
      and one with Staphylococcus lugdunensis. One S.aureus was methicillin resistant
      (MRSA). The other was clindamycin and erythromycin resistant. CONCLUSION:
      Surveillance of health-care associated infections in a setting with limited
      resources is challenging but feasible. Effective post-discharge surveillance was
      essential for the estimation of the incidence rate of SSSI following caesarean
      deliveries. This surveillance led to a peer-review of medical practices.

PMID- 23949293
TI  - Human papillomavirus detection in Moroccan patients with bladder cancer.
AB  - INTRODUCTION: Human papillomavirus (HPV) is associated with more human cancers
      than any other virus. Many studies have investigated the association between
      bladder cancer and HPV but the results remain controversial. The aim of the
      present study is to evaluate whether HPV have an etiological role in bladder
      carcinogenesis among Moroccan patients. METHODOLOGY: Forty-eight fresh biopsies
      (43 bladder tumors and 5 non-tumor samples) were collected for this purpose.
      Nested PCR with the consensus MY09/MY11 and GP5+/GP6+ primers was performed to
      detect the presence of HPV L1 gene DNA. RESULTS: The results showed that 52.4% of
      bladder cancer patients were positive for HPV. Subsequent DNA sequencing of
      positive cases of HPV revealed the presence of HPV16 in 95.5% of bladder tumor
      samples. The occurrence of HPV infection varies according to clinicopathological
      features, but there is no significant correlation between the viral infection and
      tumor stage or grade. In addition, statistical analysis demonstrated that there
      is no association between age or sex and HPV infection. CONCLUSION: Our data
      indicate for the first time that bladder tumors from Moroccan patients harbor HR
      HPV genotypes, especially HPV16, and thereby suggest that this virus may play a
      causative role in bladder cancer.

PMID- 23949294
TI  - Treatment as prevention in resource-limited settings: is it feasible to maintain
      HIV viral load suppression over time?
AB  - INTRODUCTION: Recently, there has been increasing interest in the role of
      "treatment as prevention" (TasP). Some of the questions regarding TasP strategies
      arise from the perceived difficulties in achieving and maintaining viral load
      (VL) suppression over time and the risk of emergence of viral resistance that
      could compromise future treatment options. This study was conducted to assess
      these questions in a resource-limited setting. METHODOLOGY: We performed a
      retrospective observational study of HIV-infected patients diagnosed in the pre
      HAART era on follow-up at a private center from Buenos Aires, Argentina. Socio
      demographic, clinical, and laboratory data were extracted from clinical charts.
      Analyses were performed to test for potential associations of selected variables
      with current virologic failure or use of third-line drugs. RESULTS: Of 619
      patients on follow-up, 82 (13.2%) were diagnosed in the pre-HAART era. At the
      time of our study, 79 (96.3%) patients were on HAART, with a median duration of
      14 years (IQR 12-15) of therapy, and exposure to mono or dual nucleoside reverse
      transcriptase inhibitors regimens in 47.8% of cases. Sixty-nine patients (87.3%)
      had undetectable VL, 37 (46.8%) never presented virologic failure, and 19 (24.1%)
      experienced only one failure. Thirteen patients (16.5%) were receiving third-line
      ART regimens, with an average of 2.7-fold more virologic failures than those on
      first- or second-line regimens (p = 0.007). CONCLUSIONS: Maintaining viral load
      suppression over time in resource-limited-settings is feasible.

PMID- 23949295
TI  - Clinical and laboratory predictors of outcome in cerebral malaria in suburban
      Nigeria.
AB  - INTRODUCTION: Cerebral malaria (CM) is an important cause of morbidity and
      mortality among children living in the tropics. The present study was conducted
      to update the knowledge on cerebral malaria in children. METHODOLOGY: This was a
      prospective study conducted between June 2009 and February 2010. Consecutive
      children who met the clinical and parasitological diagnostic criteria for CM were
      admitted and studied. Demographic, essential history, clinical examination
      findings and laboratory results were recorded and analyzed. Outcome in survivors
      (presence or absence of neurological deficits) were determined at discharge.
      RESULTS: Out of 1,202 children admitted during the study period, 66 (5.5%) had
      CM: 40 boys and 26 girls. Ages ranged from 2 to 128 months (mean: 41.6 +/- 27.1
      months). Fever (100%), coma (100%) and convulsion (89%) were the commonest
      presenting symptoms, while unsteady gait, speech, auditory and visual impairment
      were the commonest neurological deficits at discharge. Fifty-seven (86.4%)
      patients survived while nine (13.6%) died. Of the 57 survivors, 35 (61.4%)
      recovered completely, while 22 (38.6%) had neurological deficits at discharge.
      Identified clinical and laboratory predictors of mortality in CM included: age
      less than 3 years (p = 0.031), abnormal breathing pattern (p = 0.023), absent
      corneal reflex (p = 0.005), absent pupillary reflex (p = 0.047), retinal
      haemorrhage (p = 0.029), hypoglycaemia (p = 0.002) and leucocytosis (p = 0.040).
      CONCLUSION: CM is associated with high mortality and serious sequelae. Affected
      children should be given proactive management and monitored closely to reduce the
      frequency of adverse outcomes.

PMID- 23949296
TI  - Oropharyngeal candidiasis and Candida colonization in HIV positive patients in
      northern India.
AB  - INTRODUCTION: Oropharyngeal candidiasis (OPC) is the most common opportunistic
      fungal infection reported in human immunodeficiency virus (HIV) positive patients
      worldwide. This prospective study was undertaken to investigate OPC and Candida
      colonization (CC) and their correlation with CD4+ cell counts and antiretroviral
      therapy (ART) in HIV-positive patients. METHODOLOGY: In total, 190 HIV-positive
      patients were enrolled for study in three groups as follows: Group A, 90 patients
      without ART; Group B, 100 patients undergoing treatment with ART; and Group C, 75
      HIV-negative control patients. All HIV patients underwent clinical examination
      and were subjected to CD4+ cell counts. Swabs were collected from the oral cavity
      of all individuals and plated on Sabouraud's dextrose agar. Identification of
      Candida species was performed by conventional methods. RESULTS: Candida species
      were isolated in 84/190 (44.2%) and 20/75 (26.6%) of the HIV-positive subjects
      and controls respectively (p<0.01). OPC was noted in 21/190 (11%) of the HIV
      positive patients. Candida albicans was the most frequently isolated species.
      Patients with CD4+ cell counts <= 200 cells/mm3 were significantly (p<0.001) more
      frequently colonized (37/63; 58.7%) and infected (18/21; 85.7 %) with Candida
      species. Candida species was seen in patients with CC and OPC with CD4+cell
      counts between 201 and 500 (21/63; 33.4% vs 3/21; 14.3%) and > 500 cell/mm3
      (5/63; 7.9% versus 0/21 0%) respectively. CONCLUSION: OPC and Candida
      colonization occur more frequently in HIV-positive patients with CD4+ cell counts
      <= 200 cell/mm3. ART significantly reduces OPC. C. albicans is the most
      frequently isolated species in both OPC and colonization, suggesting endogenous
      infection.

PMID- 23949297
TI  - Children and cutaneous leishmaniasis: a clinical report and review.
AB  - INTRODUCTION: Mashhad, located in north-east Iran, is one of the most important
      regions for cutaneous leishmaniasis (CL) due to Leishmania tropica. Children
      account for 7-10% of the infected population in the endemic areas. Despite the
      high sensitivity and susceptibility of this age group, no comprehensive study has
      yet investigated the clinical characteristics and demographic data in children in
      our region. Therefore, we aimed to study the clinical features and demographic
      information in children visiting the Leishmania clinic of two main teaching
      hospitals. METHODOLOGY: In a cross-sectional study all the required data were
      gathered from the children's records available at the cutaneous leishmaniasis
      clinics of Ghaem and Imam Reza hospitals during October 2008 to September 2011.
      Data included the patient's age, sex, lesion chronicity and distribution, the
      clinical features, and the involved body parts. Descriptive statistical tests and
      SPSS version 11.5 were used for data analyses. RESULTS: Among the 8,801 studied
      files, 689 (7%) were related to children under the age of 13. Female to male
      ratio was 0.9 with the highest prevalence in the 6-9 year age group. Regarding
      disease chronicity, the most common types were acute cases with a 71% prevalence
      rate. The face was the most involved body part (77.2%) and papules with 37%
      prevalence were the most common type of lesions seen. CONCLUSION: Childhood
      cutaneous leishmaniasis accounts for a major portion of CL in north-east Iran,
      has no apparent sex preference, and its clinical spectrum does not remarkably
      differ from that of adult CL.

PMID- 23949298
TI  - Detection of extended spectrum beta-lactamases-producing isolates and effect of
      AmpC overlapping.
AB  - INTRODUCTION: Few reports about the prevalence and genetic basis of extended
      spectrum beta-lactamases (ESBLs) are available from Saudi Arabia. We sought to
      determine the prevalence of ESBL-producing Enterobacteriaceae in a university
      hospital in eastern Saudi Arabia and to characterize the ESBLs produced by these
      isolates at the molecular level. METHODOLOGY: All clinical isolates of
      Escherichia coli, Klebsiella spp., and Proteus spp. collected over two years were
      evaluated for susceptibility to a panel of antimicrobials and were analyzed for
      the ESBL phenotype using screening and confirmatory tests. ESBL-positive isolates
      were then screened for the presence of genes encoding CTX-M, SHV, and TEM beta
      lactamases by PCR. RESULTS AND CONCLUSIONS: The overall prevalence of ESBL
      producing isolates was 4.8% (253/5256). Most isolates (80%) were from the
      inpatient department. The ESBL phenotype was more frequently detected in K.
      pneumonia. CTX-M genes were the most prevalent ESBL genes, detected in 82% of the
      studied isolates. The ESBL producers demonstrated a high multidrug resistance
      rate (96.6%). In transconjugation assay, the same ESBL gene pattern was
      transmitted from 29.7% of K. pneumoniae donors to the recipient strain, and the
      latter exhibited concomitant decreased aminoglycosides and co-trimoxazole
      susceptibility. We observed the presence of ESBL screen-positive but confirmatory
      negative isolates (8.9%). Phenotypic tests for the production of AmpC beta
      lactamase tested positive in 52% of these isolates. Further studies are needed
      for appropriate detection of concomitant ESBL and AmpC enzyme production among
      such isolates. Continued surveillance and judicious antibiotic usage together
      with the implementation of efficient infection control measures are absolutely
      required.

PMID- 23949299
TI  - Faecal carriage of ESBL-producing Enterobacteriaceae and carbapenem-resistant
      Gram-negative bacilli in community settings.
AB  - INTRODUCTION: The aim of this study was to determine the prevalence of intestinal
      carriage of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae
      and carbapenem-resistant Gram-negative bacilli in the community in Buenos Aires,
      Argentina. METHODOLOGY: Faecal samples from 164 non-hospitalized patients were
      cultured on CHROMagar KPC and CHROMagar ESBL plates. Isolates resistant to third
      generation cephalosporins or carbapenems were selected for further study. The
      minimal inhibitory concentration (MIC) of the isolates was determined using the E
      test method. The phenotypic detection of ESBLs and carbapenemases was performed
      using the double-disc synergy test. RESULTS: The rate of faecal carriage of
      Enterobacteriaceae resistant to third-generation cephalosporins was 26.8%.
      Escherichia coli represented a large majority (75%) of the isolates recovered.
      Thirty-three ESBL-producing isolates were detected from 31 faecal samples (18.9%
      of the collected specimens). Eight carbapenem-resistant Gram-negative bacilli
      were recovered from eight specimens (4.9%). CONCLUSIONS: This study revealed a
      high prevalence of faecal carriage of multidrug-resistant Gram-negative bacteria,
      including ESBLs, in Buenos Aires. Therefore, the use of surveillance cultures
      will be helpful for tracking and monitoring the spread of ESBL-producing
      Enterobacteriaceae within community settings.

PMID- 23949300
TI  - Impact of migration on the occurrence of new cases of Chagas disease in Buenos
      Aires city, Argentina.

PMID- 23949301
TI  - Urban outbreak of acute orally acquired Chagas disease in Tachira, Venezuela.

PMID- 23949302
TI  - Valproic Acid attenuates disease symptoms and increases endogenous myelin repair
      by recruiting neural stem cells and oligodendrocyte progenitors in experimental
      autoimmune encephalomyelitis.
AB  - BACKGROUND: inefficient remyelination of demyelinated plaques in multiple
      sclerosis (ms) leads to secondary axon degeneration and progressive disability.
      therapies that potentiate remyelination would be of immense help for managing MS.
      OBJECTIVE: Here, we report the effects of valproic acid (VPA) on focal
      experimental autoimmune encephalomyelitis (fEAE). METHODS: fEAE was induced in
      Wistar rats by immunizing the animals with guinea pig spinal cord homogenate
      emulsified in complete Freund's adjuvant and with pertussis toxin (PT) injection
      into the spinal cord at the level of T8 vertebra on day 18 after immunization.
      VPA 300 mg/kg was applied for 4 days after or 8 days before PT administration.
      Behavioral evaluation, histological assessment and immunohistofluorescence assays
      were used to evaluate the outcomes. RESULTS: VPA administration had no effect on
      the development of symptoms, but after discontinuing VPA, animals showed faster
      recovery. Eight days of pretreatment with VPA accelerated the recovery phase of
      EAE and increased the number of remyelinated axons in the lesion area. VPA
      pretreatment also increased the recruitment of neural stem cells and
      oligodendrocyte precursors within the lesion. CONCLUSIONS: Results suggest VPA as
      a potential therapy for remyelinating the lesions in MS and for faster recovery
      from disease relapses. The effect of VPA seems to be mediated by endogenous
      progenitors recruitment.

PMID- 23949303
TI  - Effect of caloric restriction and AMPK activation on hepatic nuclear receptor,
      biotransformation enzyme, and transporter expression in lean and obese mice.
AB  - PURPOSE: Fatty liver alters liver transporter expression. Caloric restriction
      (CR), the recommended therapy to reverse fatty liver, increases Sirtuin1
      deacetylase activity in liver. This study evaluated whether CR and CR mimetics
      reversed obesity-induced transporter expression in liver and hepatocytes.
      METHODS: mRNA and protein expression was determined in adult lean (lean) and
      leptin-deficient obese (OB) mice fed ad libitum or placed on 40% (kCal) reduced
      diet. Hepatocytes were isolated from lean and OB mice, treated with AMP Kinase
      activators, and gene expression was determined. RESULTS: CR decreased Oatp1a1,
      Oatp1b2, and Abcb11 mRNA expression in lean, but not OB mice. CR increased Abcc2
      mRNA OB livers, whereas protein expression increased in both genotypes. CR
      increased Abcc3 protein expression increased in OB livers. CR did not alter
      Abcc1, 4 and 5 mRNA expression in lean mice but decreased expression in livers of
      OB mice. CR increased Abcc4 protein in lean, but not OB mice. CONCLUSIONS: CR
      restriction reversed the expression of some, but not all transporters in livers
      of OB mice. Overall, these data indicate a potential for CR to restore some
      hepatic transporter changes in OB mice, but suggest a functional leptin axis is
      needed for reversal of expression for some transporters.

PMID- 23949304
TI  - Development of a high efficiency dry powder inhaler: effects of capsule chamber
      design and inhaler surface modifications.
AB  - PURPOSE: The objective of this study was to explore the performance of a high
      efficiency dry powder inhaler (DPI) intended for excipient enhanced growth (EEG)
      aerosol delivery based on changes to the capsule orientation and surface
      modifications of the capsule and device. METHODS: DPIs were constructed by
      combining newly designed capsule chambers (CC) with a previously developed three
      dimensional (3D) rod array for particle deagglomeration and a previously
      optimized EEG formulation. The new CCs oriented the capsule perpendicular to the
      incoming airflow and were analyzed for different air inlets at a constant
      pressure drop across the device. Modifications to the inhaler and capsule
      surfaces included use of metal dispersion rods and surface coatings.
      Aerosolization performance of the new DPIs was evaluated and compared with
      commercial devices. RESULTS: The proposed capsule orientation and motion pattern
      increased capsule vibrational frequency and reduced the aerosol MMAD compared
      with commercial/modified DPIs. The use of metal rods in the 3D array further
      improved inhaler performance. Coating the inhaler and capsule with PTFE
      significantly increased emitted dose (ED) from the optimized DPI. CONCLUSIONS:
      High efficiency performance is achieved for EEG delivery with the optimized DPI
      device and formulation combination producing an aerosol with MMAD < 1.5 MUm,
      FPF<5 MUm/ED > 90%, and ED > 80%.

PMID- 23949306
TI  - Behavioral and life-history evidence for interspecific competition in the larvae
      of two heliconian butterflies.
AB  - Interspecific competition in herbivorous insects remains a controversial issue.
      To date, many studied systems have not met assumptions of the traditional
      competition theory, and a new paradigm has been emerging. We examined the
      behavioral and life-history consequences of common host plant use of Heliconius
      erato and Dryas iulia (Nymphalidae) in relation to Passiflora suberosa
      (Passifloraceae). Larvae of the former use the apical portion of this host; the
      latter is presumably able to explore all plant parts. We assessed host use
      pattern in relation to leaf age, when reared either alone (D. iulia) or together
      (D. iulia and H. erato). Larval feeding choice tests with respect to leaf age
      were performed, and performance was recorded. Observations were made to assess
      antagonistic behavior of H. erato and D. iulia towards each other, if any.
      Similarly to H. erato, D. iulia fed on the young leaves significantly more than
      the mature ones; larvae were not induced to prefer mature leaves. First instars
      of H. erato used only the apical parts of P. suberosa and displayed aggressive
      behavior towards D. iulia, which moved to the lower shoot portions. Larval
      mortality and development time of both species significantly increased when
      reared together; such performance costs were more pronounced in D. iulia than H.
      erato. Our study gathers evidences that use of P. suberosa by these heliconian
      butterflies represent a case of competitive exclusion resulting in niche
      differentiation, where costs are higher for D. iulia than H. erato.

PMID- 23949307
TI  - Bechstein's bats maintain individual social links despite a complete
      reorganisation of their colony structure.
AB  - Several social mammals, including elephants and some primates, whales and bats,
      live in multilevel societies that form temporary subgroups. Despite these fission
      fusion dynamics, group members often maintain long-term bonds. However, it is
      unclear whether such individual links and the resulting stable social subunits
      continue to exist after a complete reorganisation of a society, e.g. following a
      population crash. Here, we employed a weighted network analysis on 7,109
      individual roosting records collected over 4 years in a wild Bechstein's bat
      colony. We show that, in response to a strong population decline, the colony's
      two stable social subunits fused into a non-modular social network. Nevertheless,
      in the first year after the crash, long-term bonds were still detectable,
      suggesting that the bats remembered previous individual relationships. Our
      findings are important for understanding the flexibility of animal societies in
      the face of dramatic changes and for the conservation of social mammals with
      declining populations.

PMID- 23949305
TI  - Cytokines as key players in the pathophysiology of preeclampsia.
AB  - Preeclampsia (PE) is an important, common, and dangerous complication of
      pregnancy; it causes maternal and perinatal illness and is responsible for a high
      proportion of maternal and infant deaths. PE is associated with increased blood
      pressure and proteinuria, with a whole host of other potentially serious
      complications in the mother and fetus. The maternal syndrome in PE is primarily
      that of generalized dysfunction of the maternal endothelium, and this generalized
      endothelial dysfunction appears to be part of an exaggerated systemic
      inflammatory response that involves maternal leukocytes and proinflammatory
      cytokines. This review examines evidence that points to a significant role for
      the maternal immune system; inadequate trophoblast invasion of spiral arteries
      initiates ischemia and hypoxia in the placenta, resulting in an increased release
      of proinflammatory cytokines in the placenta. Placental ischemia and hypoxia also
      cause the enhanced release of trophoblast microparticles into the maternal
      circulation which stimulates increased induction of proinflammatory cytokines and
      the activation of maternal endothelial cells. This activation results in a
      systemic, diffuse endothelial cell dysfunction which is the fundamental
      pathophysiological feature of this syndrome. Recent evidence also supports
      important roles for proinflammatory cytokines in hypertension, proteinuria, and
      edema which are characteristic features of PE.

PMID- 23949308
TI  - Enhanced accuracy of kinetic information from CT-CPMG experiments by transverse
      rotating-frame spectroscopy.
AB  - Micro-to-millisecond motions of proteins transmit pivotal signals for protein
      function. A powerful technique for the measurement of these motions is nuclear
      magnetic resonance spectroscopy. One of the most widely used methodologies for
      this purpose is the constant-time Carr-Purcell-Meiboom-Gill (CT-CPMG) relaxation
      dispersion experiment where kinetic and structural information can be obtained at
      atomic resolution. Extraction of accurate kinetics determined from CT-CPMG data
      requires refocusing frequencies that are much larger than the nuclei's exchange
      rate between states. We investigated the effect when fast processes are probed by
      CT-CPMG experiments via simulation and show that if the intrinsic relaxation rate
      (R(CT-CPMG)(2,0)) is not known a priori the extraction of accurate kinetics is
      hindered. Errors on the order of 50 % in the exchange rate are attained when
      processes become fast, but are minimized to 5 % with a priori (CT-CPMG)(2,0))
      information. To alleviate this shortcoming, we developed an experimental scheme
      probing (CT-CPMG)(2,0)) with large amplitude spin-lock fields, which specifically
      contains the intrinsic proton longitudinal Eigenrelaxation rate. Our approach was
      validated with ubiquitin and the Oscillatoria agardhii agglutinin (OAA). For OAA,
      an underestimation of 66 % in the kinetic rates was observed if (CT-CPMG)(2,0))
      is not included during the analysis of CT-CPMG data and result in incorrect
      kinetics and imprecise amplitude information. This was overcome by combining CT
      CPMG with (CT-CPMG)(2,0)) measured with a high power R1rho experiment. In
      addition, the measurement of (CT-CPMG)(2,0)) removes the ambiguities in choosing
      between different models that describe CT-CPMG data.

PMID- 23949309
TI  - Thiolated 2-methacryloyloxyethyl phosphorylcholine for an antifouling biosensor
      platform.
AB  - We developed a new building block for a protein- and cell-repellant self
      assembled monolayer (SAM) from 2-methacryloyloxyethyl phosphorylcholine (MPC) via
      a simple Michael-type addition to one mercapto group in alkanedithiol. The
      thiolated MPC can enable functionalization of a noble metal electrode to minimize
      noise signal in biosensing. 

PMID- 23949310
TI  - Differential diagnosis of cystic and alveolar echinococcosis using an
      immunochromatographic test based on the detection of specific antibodies.
AB  - Human cystic and alveolar echinococcoses are zoonotic diseases caused by the
      larval stages of Echinococcus granulosus and Echinococcus multilocularis,
      respectively. As the diseases are co-endemic in many areas of the world, a simple
      and rapid test for the differential diagnosis of cystic echinococcosis (CE) and
      alveolar echinocoocosis (AE) is needed. Here, we describe the development of an
      immunochromatographic test (ICT) using crude hydatid cyst fluid and a recombinant
      18-kDa protein (rEm18) as antigens for the detection of E. granulosus and E.
      multilocularis antibodies in serum samples. The ICT was evaluated with serum
      samples from 195 echinococcosis patients from different endemic areas in
      northwestern China. These included 144 from CE patients, 51 from AE patients, 67
      from patients with other parasitic diseases, 13 from patients with serous hepatic
      cysts, and 60 from healthy individuals. The sensitivity and specificity of the
      ICT for CE were 91.0 and 96.9% and for AE were 98.0 and 99.3% with diagnostic
      efficiencies of 94.1 and 99.1%, respectively. No significant differences and high
      degrees of agreement were found between the ICT and an enzyme-linked
      immunosorbent assay for both CE and AE. Five serum samples from cysticercosis
      patients and one serum sample from a healthy control were found positive for CE
      with the ICT. These findings indicate that this test allows for discrimination
      between both forms of human echinococcosis. In conclusion, the ICT developed in
      this study is a promising tool for the simultaneous detection and discrimination
      of CE and AE. This test will be useful for serodiagnosis of CE and AE in clinical
      settings and screening programs.

PMID- 23949311
TI  - Genome-wide screening identifies Plasmodium chabaudi-induced modifications of DNA
      methylation status of Tlr1 and Tlr6 gene promoters in liver, but not spleen, of
      female C57BL/6 mice.
AB  - Epigenetic reprogramming of host genes via DNA methylation is increasingly
      recognized as critical for the outcome of diverse infectious diseases, but
      information for malaria is not yet available. Here, we investigate the effect of
      blood-stage malaria of Plasmodium chabaudi on the DNA methylation status of host
      gene promoters on a genome-wide scale using methylated DNA immunoprecipitation
      and Nimblegen microarrays containing 2,000 bp oligonucleotide features that were
      split into -1,500 to -500 bp Ups promoters and -500 to +500 bp Cor promoters,
      relative to the transcription site, for evaluation of differential DNA
      methylation. Gene expression was analyzed by Agilent and Affymetrix microarray
      technology. Challenging of female C57BL/6 mice with 10(6) P. chabaudi-infected
      erythrocytes resulted in a self-healing outcome of infections with peak
      parasitemia on day 8 p.i. These infections induced organ-specific modifications
      of DNA methylation of gene promoters. Among the 17,354 features on Nimblegen
      arrays, only seven gene promoters were identified to be hypermethylated in the
      spleen, whereas the liver exhibited 109 hyper- and 67 hypomethylated promoters at
      peak parasitemia in comparison with non-infected mice. Among the identified genes
      with differentially methylated Cor-promoters, only the 7 genes Pigr, Ncf1, Klkb1,
      Emr1, Ndufb11, and Tlr6 in the liver and Apol6 in the spleen were detected to
      have significantly changed their expression. Remarkably, the Cor promoter of the
      toll-like receptor Tlr6 became hypomethylated and Tlr6 expression increased by
      3.4-fold during infection. Concomitantly, the Ups promoter of the Tlr1 was
      hypermethylated, but Tlr1 expression also increased by 11.3-fold. TLR6 and TLR1
      are known as auxillary receptors to form heterodimers with TLR2 in plasma
      membranes of macrophages, which recognize different pathogen-associated molecular
      patterns (PAMPs), as, e.g., intact 3-acyl and sn-2-lyso-acyl
      glycosylphosphatidylinositols of P. falciparum, respectively. Our data suggest
      therefore that malaria-induced epigenetic fine-tuning of Tlr6 and Tlr1 through
      DNA methylation of their gene promoters in the liver is critically important for
      initial recognition of PAMPs and, thus, for the final self-healing outcome of
      blood-stage infections with P. chabaudi malaria.

PMID- 23949312
TI  - Fusidic acid is an effective treatment against Toxoplasma gondii and Listeria
      monocytogenes in vitro, but not in mice.
AB  - Fusidic acid is a bacteriostatic antibiotic that inhibits the growth of bacteria
      by preventing the release of translation elongation factor G (EF-G) from the
      ribosome. The apicomplexan parasite Toxoplasma gondii has an orthologue of
      bacterial EF-G that can complement bacteria and is necessary for parasite
      virulence. Fusidic acid has been shown to be effective in tissue culture against
      the related pathogen Plasmodium falciparum, and current drug treatments against
      T. gondii are limited. We therefore investigated the therapeutic value of fusidic
      acid for T. gondii and found that the drug was effective in tissue culture, but
      not in a mouse model of infection. To determine whether this trend would occur in
      another intracellular pathogen that elicits a T helper 1-type immune response, we
      tested the efficacy of fusidic acid for the bacterium Listeria monocytogenes.
      Similar to its effects on T. gondii, fusidic acid inhibits the growth of L.
      monocytogenes in vitro, but not in mice. These findings highlight the necessity
      of in vivo follow-up studies to validate in vitro drug investigations. 

PMID- 23949313
TI  - No difference between posaconazole and fluconazole antifungal prophylaxis and
      mycological diagnostics except costs in patients undergoing AML chemotherapy: a 1
      year "real-life" evaluation.

PMID- 23949315
TI  - Rapid detection of IDH2 (R140Q and R172K) mutations in acute myeloid leukemia.
AB  - NADP-dependent enzyme isocitrate dehydrogenase (IDH) mutations, IDH1 and IDH2,
      have been described in acute myeloid leukemia (AML) using next generation
      sequencing approaches. IDH2 mutations are heterozygous; they alter a single
      arginine residue at position 140 or 172 and have distinct prognostic
      significance. The current detection methods of IDH2 mutations are laborious and
      time consuming as they require DNA sequencing. Herein, we report a new allele
      specific oligonucleotide-polymerase chain reaction (ASO-PCR) method to detect the
      IDH2 mutations. Analysis of leukemic DNA samples from 120 AML patients enabled to
      identify IDH2 mutations in 22 cases which were confirmed by direct DNA
      sequencing. Of these, 17 harbored IDH2 (R140Q) and 5 IDH2 (R172K) mutations.
      Serial dilution experiments showed that the assay enable to detect mutations in
      10-3 dilutions. Our ASO-PCR method appears useful for routine diagnostic
      screening of these prognostically relevant alterations in AML and may be
      conveniently included in the diagnostic workup.

PMID- 23949314
TI  - Arsenic trioxide suppressed mantle cell lymphoma by downregulation of cyclin D1.
AB  - Mantle cell lymphoma (MCL) is aggressive with poor prognosis. Due to
      t(11;14)(q13;q32), cyclin D1 is overexpressed. The in vitro activities of arsenic
      trioxide (As2O3) in MCL were investigated. In MCL lines Jeko-1 and Granta-519,
      As2O3 induced dose-dependent and time-dependent increases in apoptosis
      accompanied by cyclin D1 suppression. Downregulation of cyclin D1 resulted in
      decreased retinoblastoma protein phosphorylation, which led to repressed G1
      progression to S/G2 phases. As2O3 did not affect cyclin D1 gene transcription.
      Instead, As2O3 activated glycogen synthase kinase-3beta (by tyrosine-216
      phosphorylation) and IkappaB kinase alpha/beta (by serine-176/180
      phosphorylation), both of which phosphorylated cyclin D1 at threonine-286,
      leading to its poly-ubiquitination and degradation in the proteasome. These
      observations were recapitulated partly in primary MCL samples obtained from
      patients refractory to conventional treatment. Our findings suggested that As2O3
      might be clinically useful in MCL. 

PMID- 23949316
TI  - Strong effect of mogamulizumab on splenic residual disease of adult T cell
      leukemia/lymphoma.

PMID- 23949317
TI  - Low prevalence of cardiac siderosis in heavily iron loaded Egyptian thalassemia
      major patients.
AB  - Myocardial siderosis in thalassemia major remains the leading cause of death in
      developing countries. Once heart failure develops, the outlook is usually poor
      with precipitous deterioration and death. Cardiovascular magnetic resonance (CMR)
      can measure cardiac iron deposition directly using the magnetic relaxation time
      T2*. This allows earlier diagnosis and treatment and helps to reduce mortality
      from this cardiac affection. This study aims to determine the prevalence of
      cardiac siderosis in Egyptian patients who are heavily iron loaded and its
      relation to liver iron concentration, serum ferritin, and left ventricular
      ejection fraction. Eighty-nine beta-thalassemia patients receiving chelation
      therapy (mean age of 20.8 +/- 6.4 years) were recruited in this study. Tissue
      iron levels were determined by CMR with cardiac T2* and liver R2*. The mean +/-
      standard deviation (range) of cardiac T2* was 28.5 +/- 11.7 ms (4.3 to 53.8 ms),
      the left ventricular ejection fraction (LVEF) was 67.7 +/- 4.7 % (55 to 78 %),
      and the liver iron concentration (LIC) was 26.1 +/- 13.4 mg Fe/g dry weight (dw)
      (1.5 to 56 mg Fe/g dw). The mean serum ferritin was 4,510 +/- 2,847 ng/ml (533 to
      22,360 ng/ml), and in 83.2 %, the serum ferritin was >2,500 ng/ml. The prevalence
      of myocardial siderosis (T2* of <20 ms) was 24.7 % (mean age 20.9 +/- 7.5 years),
      with mean T2* of 12.7 +/- 4.4 ms, mean LVEF of 68.6 +/-5.8 %, mean LIC of 30.9 +/
      13 mg Fe/g dw, and median serum ferritin of 4,996 ng/ml. There was no
      correlation between T2* and age, LVEF, LIC, and serum ferritin (P = 0.65, P =
      0.085, P = 0.99, and P = 0.63, respectively). Severe cardiac siderosis (T2* of
      <10 ms) was present in 7.9 %, with a mean age of 18.4 +/- 4.4 years. Although
      these patients had a mean T2* of 7.8 +/- 1.7 ms, the LVEF was 65.1 +/- 6.2 %, and
      only one patient had heart failure (T2* of 4.3 ms and LVEF of 55 %). LIC and
      serum ferritin results were 29.8 +/- 17.0 mg/g and 7,200 +/- 6,950 ng/ml,
      respectively. In this group of severe cardiac siderosis, T2* was also not
      correlated to age (P = 0.5), LVEF (P = 0.14), LIC (P = 0.97), or serum ferritin
      (P = 0.82). There was a low prevalence of myocardial siderosis in the Egyptian
      thalassemia patients in spite of very high serum ferritin and high LIC. T2* is
      the best test that can identify at-risk patients who can be managed with
      optimization of their chelation therapy. The possibility of a genetic component
      for the resistance to cardiac iron loading in our population should be
      considered.

PMID- 23949318
TI  - Breakthrough invasive fungal diseases during echinocandin treatment in high-risk
      hospitalized hematologic patients.
AB  - The frequency of breakthrough invasive fungal diseases (IFDs) during echinocandin
      therapy is unclear. We retrospectively analyzed 534 hematologic patients treated
      with echinocandin (caspofungin, N = 55; micafungin, N = 306; anidulafungin, N =
      173). Four proven IFDs were found, caused by Candida parapsilosis (N = 2), C.
      parapsilosis and Candida glabrata (N = 1), and Fusarium species (N = 1). Four
      cases of possible IFDs were observed, all showing pulmonary infection. One case
      showed features suggestive of hepatosplenic candidiasis. Six of these eight cases
      had previously received the purine analog clofarabine. Breakthrough IFD during
      echinocandin treatment occurred infrequently (1.5 %), caused predominantly by
      Candida species. Clofarabine usage was an important risk factor.

PMID- 23949319
TI  - Short leukocyte telomere length predicts risk of diabetes in american indians:
      the strong heart family study.
AB  - Telomeres play a central role in cellular aging, and shorter telomere length has
      been associated with age-related disorders including diabetes. However, a causal
      link between telomere shortening and diabetes risk has not been established. In a
      well-characterized longitudinal cohort of American Indians participating in the
      Strong Heart Family Study, we examined whether leukocyte telomere length (LTL) at
      baseline predicts incident diabetes independent of known diabetes risk factors.
      Among 2,328 participants free of diabetes at baseline, 292 subjects developed
      diabetes during an average 5.5 years of follow-up. Compared with subjects in the
      highest quartile (longest) of LTL, those in the lowest quartile (shortest) had an
      almost twofold increased risk of incident diabetes (hazard ratio [HR] 1.83 [95%
      CI 1.26-2.66]), whereas the risk for those in the second (HR 0.87 [95% CI 0.59
      1.29]) and the third (HR 0.95 [95% CI 0.65-1.38]) quartiles was statistically
      nonsignificant. These findings suggest a nonlinear association between LTL and
      incident diabetes and indicate that LTL could serve as a predictive marker for
      diabetes development in American Indians, who suffer from disproportionately high
      rates of diabetes. 

PMID- 23949320
TI  - Sodium intake and blood pressure in children.
AB  - Elevation of blood pressure (BP) and the risk for progression to hypertension
      (HTN) is of increasing concern in children and adolescents. Indeed, it is
      increasingly recognized that target organ injury may begin with even low levels
      of BP elevation. Sodium intake has long been recognized as a modifiable risk
      factor for HTN. While it seems clear that sodium impacts BP in children, its
      effects may be enhanced by other factors including obesity and increasing age.
      Evidence from animal and human studies indicates that sodium may have adverse
      consequences on the cardiovascular system independent of HTN. Thus, moderation of
      sodium intake over a lifetime may reduce risk for cardiovascular morbidity in
      adulthood. An appetite for salt is acquired, and intake beyond our need is almost
      universal. Considering that eating habits in childhood have been shown to track
      into adulthood, modest sodium intake should be advocated as part of a healthy
      lifestyle.

PMID- 23949322
TI  - No association of the SLC1A2 rs3794087 allele with risk for essential tremor in
      the Spanish population.
AB  - BACKGROUND/AIMS: A recent genome-wide association study and other replication
      studies have suggested that the rs3794087 single nucleotide polymorphism in the
      solute carrier family 1 - glial affinity glutamate transporter-member 2 (SLC1A2)
      gene is associated with an increased risk for essential tremor (ET), and a
      replication study in an Asian cohort has shown a decreased risk for ET associated
      with the rs3794087T allele. We tried to replicate this association in a White
      Spanish population. MATERIALS AND METHODS: We analyzed the distribution of
      allelic and genotypic frequencies of rs3794087 in 202 patients with familial ET
      and 308 healthy controls using a TaqMan-based quantitative PCR assay. RESULTS:
      Genotypic and allelic frequencies of rs3794087 did not differ significantly
      between patients with ET and controls and were unrelated with the age at onset of
      tremor or sex. CONCLUSION: Our study suggests that SLC1A2 rs3794087 is not
      associated with the risk for developing familial ET in the Spanish population,
      thus subtracting relevance to SLC1A2 rs3794087 as a risk biomarker for ET.

PMID- 23949321
TI  - Hypertension-related stroke prevention in the elderly.
AB  - Hypertension is a major risk factor for cardiovascular events, including ischemic
      stroke and hemorrhagic stroke. Reduction of blood pressure by lifestyle measures
      and antihypertensive drug therapy reduces stroke in elderly men and women. The
      use of diuretics, beta blockers, calcium channel blockers, angiotensin-converting
      enzyme inhibitors, or angiotensin receptor blockers causes a similar reduction in
      reducing coronary events and stroke for a given reduction in blood pressure. The
      American College of Cardiology Foundation/American Heart Association 2011 expert
      consensus document on hypertension in the elderly recommended that the blood
      pressure should be reduced to less than 140/90 mm Hg in adults younger than 80
      years at high risk for cardiovascular events. On the basis of data from the
      Hypertension in the Very Elderly trial, these guidelines recommended that the
      systolic blood pressure should be reduced to 140 to 145 mm Hg if tolerated in
      adults aged 80 years and older. The 2013 European Society of Hypertension
      guidelines recommended that reducing blood pressure to less than 130/80 mm Hg in
      adults at high risk for cardiovascular events was unsupported by prospective
      trial data. The systolic blood pressure should be reduced to less than 140 mm Hg
      in these adults and to between 140 to 150 mm Hg in adults aged 80 years and
      older. 

PMID- 23949323
TI  - Confirmation of diosmetin 3-O-glucuronide as major metabolite of diosmin in
      humans, using micro-liquid-chromatography-mass spectrometry and ion mobility mass
      spectrometry.
AB  - Diosmin is a flavonoid often administered in the treatment of chronic venous
      insufficiency, hemorrhoids, and related affections. Diosmin is rapidly hydrolized
      in the intestine to its aglicone, diosmetin, which is further metabolized to
      conjugates. In this study, the development and validations of three new methods
      for the determination of diosmetin, free and after enzymatic deconjugation, and
      of its potential glucuronide metabolites, diosmetin-3-O-glucuronide, diosmetin-7
      O-glucuronide, and diosmetin-3,7-O-glucuronide from human plasma and urine are
      presented. First, the quantification of diosmetin, free and after deconjugation,
      was carried out by high-performance liquid chromatography coupled with tandem
      mass spectrometry, on an Ascentis RP-Amide column (150 * 2.1 mm, 5 MUm), in
      reversed-phase conditions, after enzymatic digestion. Then glucuronide
      metabolites from plasma were separated by micro-liquid chromatography coupled
      with tandem mass spectrometry on a HALO C18 (50 * 0.3 mm, 2.7 MUm, 90 A) column,
      after solid-phase extraction. Finally, glucuronides from urine were measured
      using a Discovery HSF5 (100 * 2.1 mm, 5 MUm) column, after simple dilution with
      mobile phase. The methods were validated by assessing linearity, accuracy,
      precision, low limit of quantification, selectivity, extraction recovery,
      stability, and matrix effects; results in agreement with regulatory (Food and
      Drug Administration and European Medicines Agency) guidelines acceptance criteria
      were obtained in all cases. The methods were applied to a pharmacokinetic study
      with diosmin (450 mg orally administered tablets). The mean C max of diosmetin in
      plasma was 6,049.3 +/- 5,548.6 pg/mL. A very good correlation between measured
      diosmetin and glucuronide metabolites concentrations was obtained. Diosmetin-3-O
      glucuronide was identified as a major circulating metabolite of diosmetin in
      plasma and in urine, and this finding was confirmed by supplementary experiments
      with differential ion-mobility mass spectrometry.

PMID- 23949324
TI  - Medical students teaching cardiopulmonary resuscitation to middle school
      Brazilian students.
AB  - BACKGROUND: Diseases of the circulatory system are the most common cause of death
      in Brazil. Because the general population is often the first to identify problems
      related to the circulatory system, it is important that they are trained.
      However, training is challenging owing to the number of persons to be trained and
      the maintenance of training. OBJECTIVES: To assess the delivery of a medical
      student led cardiopulmonary resuscitation (CPR) training program and to assess
      prior knowledge of CPR as well as immediate and delayed retention of CPR training
      among middle school students. METHODS: Two public and two private schools were
      selected. CPR training consisted of a video class followed by practice on
      manikins that was supervised by medical students. Multiple choice questionnaires
      were provided before, immediately after, and at 6 months after CPR training. The
      questions were related to general knowledge, the sequence of procedures, and the
      method to administer each component (ventilation, chest compression, and
      automated external defibrillation). The instructors met in a focus group after
      the sessions to identify the potential problems faced. RESULTS: In total, 147
      students completed the 6-month follow-up. The public school students had a lower
      prior knowledge, but this difference disappeared immediately after training.
      After the 6-month follow-up period, these public school students demonstrated
      lower retention. The main problem faced was teaching mouth-to-mouth
      resuscitation. CONCLUSIONS: The method used by medical students to teach middle
      school students was based on the see-and-practice technique. This method was
      effective in achieving both immediate and late retention of acquired knowledge.
      The greater retention of knowledge among private school students may reflect
      cultural factors.

PMID- 23949325
TI  - Maternal restriction of polyphenols and fetal ductal dynamics in normal
      pregnancy: an open clinical trial.
AB  - BACKGROUND: We have recently demonstrated reversal of fetal ductal constriction
      after dietary maternal restriction of polyphenol-rich foods (PRF), due to its
      inhibitory action on prostaglandin synthesis. OBJECTIVE: To test the hyphotesis
      that normal third trimester fetuses also improve ductus arteriosus dynamics after
      maternal restriction of polyphenols. METHODS: Open clinical trial with 46 fetuses
      with gestational age (GA) > 28 weeks submitted to 2 Doppler echocardiographic
      studies with an interval of at least 2 weeks, being the examiners blinded to
      maternal dietary habits. A validated food frequency questionnaire was applied and
      a diet based on polyphenol-poor foods (<30 mg/100 mg) was recommended. A control
      group of 26 third trimester fetuses was submitted to the same protocol.
      Statistics used t test for independent samples. RESULTS: Mean GA was 33 +/- 2
      weeks. Mean daily maternal estimated polyphenol intake (DMPI) was 1277 mg,
      decreasing to 126 mg after dietary orientation (p=0.0001). Significant decreases
      in systolic (SDV) and diastolic (DDV) ductal velocities, and RV/LV diameters
      ratio, as well as increase in ductal PI were observed [DSV = 1.2 +/- 0.4 m/s (0.7
      1.6) to 0.9 +/- 0.3 m/s (0.6-1.3) (p = 0.018); DDV = 0.21 +/- 0.09 m/s (0.15
      0.32) to 0.18 +/- 0.06 m/s (0.11-0.25) (p = 0.016); RV/LV ratio = 1.3 +/- 0.2
      (0.9-1.4) to 1.1 +/- 0.2 (0.8-1.3) (p=0.004); ductal PI = 2.2 +/- 0.03 (2.0-2.7)
      to 2.4 +/- 0.4(2.2-2.9) (p = 0.04)]. In the control group, with GA of 32 +/- 4
      weeks, there were no significant differences in DMPI, mean SDV, DDV, PI and RV/LV
      ratio. CONCLUSION: The oriented restriction of third trimester maternal ingestion
      of polyphenol-rich foods for a period of 2 weeks or more improve fetal ductus
      arteriosus flow dynamics and right ventricular dimensions.

PMID- 23949326
TI  - Genetic polymorphism G894T and the prognosis of heart failure outpatients.
AB  - BACKGROUND: Previous studies have analyzed the role of the genetic polymorphism
      of endothelial nitric oxide synthase on heart failure prognosis. However, there
      are no studies relating the G894T and heart failure in Brazil. OBJECTIVE: To
      evaluate the association between G894T GP and the prognosis of a sample of
      Brazilian outpatients with heart failure. METHODS: Cohort study included 145
      patients with systolic heart failure, followed for up to 40 months (mean = 22),
      at two university hospitals, in the State of Rio de Janeiro. We evaluated the
      relationship between G894T and the following outcomes: reverse remodeling,
      improvement in functional class (NYHA), and mortality and hospitalization rates.
      The diameters of the left atrium and ventricle, as well as the ejection fraction
      of the left ventricle, were evaluated at baseline and at 6 months to assess
      reverse remodeling. The improvement in functional class was evaluated after 6
      months, and mortality rate and hospitalization were evaluated during follow-up.
      Race was self-declared. G894T polymorphism was analyzed by polymerase chain
      reaction and restriction fragment length polymorphism. RESULTS: The genotypic
      frequencies were GG (40%), GT (48.3%) and TT (11.7%). The allele frequency was
      guanine (64.1%) and thiamine (35.8%). There were no differences between the
      genotype or allelic frequencies according to self-declared race, either as
      baseline characteristics. There was no relationship between genotype or allele
      frequency and the outcome measures. CONCLUSION: No association was observed
      between the G894T polymorphism (Glu298Asp) and prognosis in this sample of
      Brazilian outpatients with systolic heart failure.

PMID- 23949327
TI  - Prospective validation of the Dante Pazzanese risk score in non-ST-segment
      elevation acute coronary syndrome.
AB  - BACKGROUND: In non-ST-segment elevation acute coronary syndrome (ACS), the
      likelihood of adverse events should be estimated. Guidelines recommend risk
      stratification models for that purpose. The Dante Pazzanese risk score (DANTE
      score) is a simple risk stratification model composed with the following
      variables: age increase (0 to 9 points); history of diabetes mellitus (2 points)
      or stroke (4 points); no use of angiotensin-converting-enzyme inhibitor (1
      point); creatinine elevation (0 to 10 points); combination of troponin elevation
      and ST-segment depression (0 to 4 points). OBJECTIVE: To validate the DANTE score
      in patients with non-ST-segment elevation ACS. METHODS: Prospective,
      observational study including 457 patients, from September 2009 to October 2010.
      The patients were grouped in risk categories according to the original model
      score as follows: very low; low; intermediate; and high. The predictive ability
      of the score was assessed by using C-statistics. RESULTS: The sample comprised
      291 (63.7%) men, the mean age being 62.1 years (SD=11.04). The event death or
      (re)infarction in 30 days was observed in 17 patients (3.7%). Progressive
      increase in the proportion of events was observed as the score increased: very
      low risk = 0.0%; low risk = 3.9%; intermediate risk = 10.9%; high risk = 60.0%; p
      < 0.0001. C-statistics was 0.87 (95% CI: 0.81-0.94; p < 0.0001). CONCLUSION:
      DANTE score showed an excellent capacity to predict the specific events, and can
      be incorporated to the prognostic assessment of patients with non-ST-segment
      elevation ACS.

PMID- 23949328
TI  - Potential to link dietary patterns in the food supply and populations to health.

PMID- 23949329
TI  - The Healthy Eating Index 2005 and risk for pancreatic cancer in the NIH-AARP
      study.
AB  - BACKGROUND: Dietary pattern analyses characterizing combinations of food intakes
      offer conceptual and statistical advantages over food- and nutrient-based
      analyses of disease risk. However, few studies have examined dietary patterns and
      pancreatic cancer risk and none focused on the 2005 Dietary Guidelines for
      Americans. We used the Healthy Eating Index 2005 (HEI-2005) to estimate the
      association between meeting those dietary guidelines and pancreatic cancer risk.
      METHODS: We calculated the HEI-2005 score for 537 218 men and women in the
      National Institutes of Health-American Association of Retired Persons Diet and
      Health Study using responses to food frequency questionnaires returned in 1995
      and 1996. We used Cox proportional hazards regression to estimate hazard ratios
      (HRs) and 95% confidence intervals (CIs) for risk of pancreatic cancer according
      to HEI-2005 quintiles and explored effect modification by known risk factors. P
      interaction values were calculated using the Wald test. All statistical tests
      were two-sided. RESULTS: We identified 2383 incident, exocrine pancreatic cancer
      cases (median = 10.5 years follow-up). Comparing participants who met the most
      dietary guidelines (Q5) with those who met the fewest guidelines (Q1), we
      observed a reduced risk of pancreatic cancer (HR = 0.85, 95% CI = 0.74 to 0.97).
      Among men there was an interaction by body mass index (P interaction = .03), with
      a hazard ratio of 0.72 (95% CI = 0.59 to 0.88) comparing Q5 vs Q1 in
      overweight/obese men (body mass index >= 25 kg/m(2)) but no association among
      normal weight men. CONCLUSIONS: Our findings support the hypothesis that
      consuming a high-quality diet, as scored by the HEI-2005, may reduce the risk of
      pancreatic cancer.

PMID- 23949330
TI  - An investigation into the relationship between metabolic responses and energy
      regulation in antibody-producing cell.
AB  - Energy-efficient metabolic responses were often noted in high-productive
      cultures. To better understand these metabolic responses, an investigation into
      the relationship between metabolic responses and energy regulation was conducted
      via a comparative analysis among cultures with different energy source supplies.
      Both glycolysis and glutaminolysis were studied through the kinetic analyses of
      major extracellular metabolites concerning the fast and slow cell growth stages,
      respectively, as well as the time-course profiles of intracellular metabolites.
      In three cultures showing distinct antibody productivities, the amino acid
      metabolism and energy state were further examined. Both the transition of lactate
      from production to consumption and steady intracellular pools of pyruvate and
      lactate were observed to be correlated with efficient energy regulation. In
      addition, an efficient utilization of amino acids as the replenishment for the
      TCA cycle was also found in the cultures with upregulated energy metabolism. It
      was further revealed that the inefficient energy regulation would cause low cell
      productivity based on the comparative analysis of cell growth and productivity in
      cultures having distinct energy regulation.

PMID- 23949331
TI  - Purification and characterization of heat-tolerant protease produced by Bacillus
      polyfermenticus SCD.
AB  - A protease produced by Bacillus polyfermenticus SCD was purified and
      characterized as a new detergent material. The protease was purified from
      supernatant produced by B. polyfermenticus SCD, by ammonium sulfate
      precipitation, ion-exchange chromatography on a DEAE-Sephadex A-50, and finally
      gel filtration chromatography on Sephadex G-50. The molecular mass of this enzyme
      was 44 kDa based on SDS-PAGE. The optimum temperature and pH were 50 degrees C
      and pH 8.0. The ranges of its stability to the pH and temperature were 7.0 to 9.0
      and under 40 degrees C, respectively. The enzyme was highly stable in the
      presence of the surfactants like Triton X-100 (0.1%), showing a 2-fold increase
      in its proteolytic activity. However, the enzyme was slightly inhibited by the
      chelating agent EDTA (1 mM). The enzyme has a maximum activity at 50 degrees C
      and the activity can be increased by surfactants such as Triton X-100 and Tween
      80.

PMID- 23949332
TI  - Metagenomic analysis of fungal communities inhabiting the fairy ring zone of
      Tricholoma matsutake.
AB  - Tricholoma matsutake, an ectomycorrhiza that has mutual relationships with the
      rootlet of Pinus denisflora, forms a fruiting body that serves as a valuable food
      in Asia. However, the artificial culture of this fungus has not been successful.
      Soil fungi, including T. matsutake, coexist with many other microorganisms and
      plants; therefore, complex microbial communities have an influence on the
      fruiting body formation of T. matsutake. Here, we report on the structures of
      fungal communities associated with the fairy ring of T. matsutake through the
      pyrosequencing method. Soil samples were collected inside the fairy ring zone, in
      the fairy ring zone, and outside the fairy ring zone. A total of 37,125
      sequencing reads were obtained and 728 to 1,962 operational taxonomic units
      (OTUs) were observed in the sampling zones. The fairy ring zone had the lowest
      OTUs and the lowest fungal diversity of all sampling zones. The number of OTUs
      and fungal taxa inside and outside the fairy ring zone was, respectively, about 2
      times and 1.5 times higher than the fairy ring. Taxonomic analysis showed that
      each sampling zone has different fungal communities. In particular, out of 209
      genera total, 6 genera in the fairy ring zone, such as Hemimycena, were uniquely
      present and 31 genera, such as Mycena, Boletopsis, and Repetophragma, were
      specifically absent. The results of metagenomic analysis based on the
      pyrosequencing indicate a decrease of fungal communities in the fairy ring zone
      and changes of fungal communities depending on the fairy ring growth of T.
      matsutake. 

PMID- 23949333
TI  - Different effects of acidic pH shock on the prodiginine production in
      Streptomyces coelicolor M511 and SJM1 mutants.
AB  - The changes in prodiginines productions caused by pH shock culture of
      Streptomyces coelicolor strains were estimated. In Streptomyces coelicolor M511,
      undecylprodiginine and streptorubin B productions increased 1.8-fold (37.22 mg/g)
      and 2.5-fold (18.61 mg/g), respectively, by pH shock (from 7.2 to 4.0). In
      contrast, this resulted in the significantly decreased prodigignines production
      in the redP deletion mutant SJM1; 3.7-fold for undecylprodiginine, 4.4-fold for
      streptorubin B, 5.2-fold for methylundecylprodiginine, and 6.4-fold for
      methyldodecylundecylprodiginine, respectively. RT-PCR analyses showed that,
      during pH shock, expression of redD, the transcription activator gene, was
      increased while the expression of fabH, the decarboxylative condensation enzyme
      gene in fatty acid biosynthesis, was decreased in both strains. The enhanced redD
      expression was in good accordance with the increased total prodiginines
      production of M511. However, for SJM1 mutant, the decrease of fabH expression
      occurred more strikingly, such that it became almost completely turned off during
      acidic pH shock culture. Therefore, a down-regulation of fabH was considered to
      be the cause of decreased amount of total prodiginines produced, although redD
      expression was high in SJM1 mutant. 

PMID- 23949334
TI  - Little children with big worries: addressing the needs of young, anxious children
      and the problem of parent engagement.
AB  - Anxiety disorders in preschool-age children represent an important clinical
      problem due to high prevalence, substantial impairment, persistence, and
      associated risk for later emotional problems. Early intervention may mitigate
      these problems by capitalizing on a strategic developmental period. Elevated
      neuroplasticity, availability of screening tools, and the potential to modify
      parenting practices position anxiety as a good candidate for early intervention
      and preventive efforts. While some novel interventions show promise, the broad
      success of such programs will largely depend on parent engagement. Since parents
      are less likely to identify and seek help for anxiety problems compared to other
      childhood behavior problems, especially in a preventive manner, methods for
      understanding parents' decisions to participate and enhancing levels of
      engagement are central to the success of early childhood anxiety prevention and
      intervention. Understanding these processes is particularly important for
      families characterized by sociodemographic adversity, which have been
      underrepresented in anxiety treatment research. This review summarizes the
      developmental phenomenology of early emerging anxiety symptoms, the rationale for
      early intervention, and the current state of research on interventions for young,
      anxious children. The roles of parent engagement and help-seeking processes are
      emphasized, especially among economically disadvantaged and ethnic minority
      communities who are acutely at risk. Evidence-based strategies to enhance parent
      engagement to facilitate the development and dissemination of efficacious
      programs are offered. 

PMID- 23949336
TI  - Association of overexpression of hexokinase II with chemoresistance in epithelial
      ovarian cancer.
AB  - This aim of this study was to evaluate the relationship between hexokinase II
      expression and chemoresistance in epithelial ovarian cancer. One hundred and
      eleven paraffin-embedded specimens from patients with epithelial ovarian cancer
      were immunohistochemically stained for hexokinase II. Subsequently, the
      association between hexokinase II overexpression and clinicopathologic
      characteristics including chemoresistance was assessed. Survival analyses were
      also performed for evaluating the prognostic value of hexokinase II
      overexpression. Tumor recurrence within 6 months after termination of first-line
      chemotherapy was considered to indicate chemoresistance. Hexokinase II
      overexpression was associated with chemoresistance (p = 0.029) and was an
      independent risk factor for chemoresistance [odds ratio (OR) 3.37; 95 %
      confidence interval (CI) 1.07-10.62; p = 0.038] along with non-optimal debulking
      surgery (OR 4.93; 95 % CI 1.43-16.98; p = 0.011). Hexokinase II overexpression
      was significantly associated with decreased progression-free survival (p = 0.002)
      and showed a similar trend for overall survival (p = 0.101). Cox regression
      analysis revealed that hexokinase II overexpression was an independent prognostic
      factor for early recurrence (hazard ratio 2.63; 95 % CI 1.40-4.92; p = 0.002).
      Our findings suggest that hexokinase II overexpression is associated with short
      progression-free survival, which could be associated with chemoresistance in
      epithelial ovarian cancer.

PMID- 23949335
TI  - An informatics approach to integrating genetic and neurological data in speech
      and language neuroscience.
AB  - A number of heritable disorders impair the normal development of speech and
      language processes and occur in large numbers within the general population.
      While candidate genes and loci have been identified, the gap between genotype and
      phenotype is vast, limiting current understanding of the biology of normal and
      disordered processes. This gap exists not only in our scientific knowledge, but
      also in our research communities, where genetics researchers and speech,
      language, and cognitive scientists tend to operate independently. Here we
      describe a web-based, domain-specific, curated database that represents
      information about genotype-phenotype relations specific to speech and language
      disorders, as well as neuroimaging results demonstrating focal brain differences
      in relevant patients versus controls. Bringing these two distinct data types into
      a common database ( http://neurospeech.org/sldb ) is a first step toward bringing
      molecular level information into cognitive and computational theories of speech
      and language function. One bridge between these data types is provided by densely
      sampled profiles of gene expression in the brain, such as those provided by the
      Allen Brain Atlases. Here we present results from exploratory analyses of human
      brain gene expression profiles for genes implicated in speech and language
      disorders, which are annotated in our database. We then discuss how such datasets
      can be useful in the development of computational models that bridge levels of
      analysis, necessary to provide a mechanistic understanding of heritable language
      disorders. We further describe our general approach to information integration,
      discuss important caveats and considerations, and offer a specific but
      speculative example based on genes implicated in stuttering and basal ganglia
      function in speech motor control. 

PMID- 23949344
TI  - Accurate adsorption energies of small molecules on oxide surfaces: CO-MgO(001).
AB  - A hybrid MP2:DFT + D optimization method is applied using a 3 * 3 * 2 cluster
      model (Mg9O9) embedded in a 4 * 4 * 4 slab model. The calculated CO-Mg(2+)
      distance is 248 pm, and the calculated CO frequency (blue) shift is 20 cm(-1), 6
      cm(-1) larger than the experimental value. For the structure obtained, MP2
      calculations with basis set extrapolation on a series of cluster models of
      increasing size are performed. Taking into account the difference in the periodic
      limit at the DFT + D level, 20.9 +/- 0.7 kJ mol(-1) is obtained as the estimate
      for the full periodic MP2 limit for the energy of CO desorption from the MgO(001)
      surface. CCSD(T) corrections are evaluated for the Mg9O9 cluster model using an
      augmented double-zeta basis set. Basis set extension effects are examined for
      smaller models. For a loading of Theta = 1/8, the estimated CCSD(T) value is 21.0
      +/- 1.0 kJ mol(-1), which is 0.4 +/- 1.0 kJ mol(-1) larger than the (electronic)
      desorption energy derived in this study from TPD desorption barriers reported in
      the literature. 

PMID- 23949338
TI  - Tocilizumab: a new therapy for large vessel vasculitis.
AB  - Large vessel vasculitis represents mainly two main diseases: giant cell arteritis
      and Takayasu arteritis. Recent advancements in the treatment for different
      rheumatic diseases refractory to disease-modifying antirheumatic agents with
      biologic agents have resulted in remarkable efficacy and tolerability. However,
      treatments for large vessel vasculitis (LVV) with tumor necrosis factor-alpha
      inhibitors have yielded conflicting results. Recently, very promising results
      have been reported in patients treated with tocilizumab. The purpose of this
      review is to summarize the current treatment strategies of LVV and the recent
      evidence on the use of tocilizumab in LVV.

PMID- 23949337
TI  - Impact of methotrexate on oxidative stress and apoptosis markers in psoriatic
      patients.
AB  - Methotrexate (MTX), a cytotoxic chemotherapeutic agent, is considered an
      effective drug in the treatment of psoriasis. The aim of this study was to find
      out whether the effect of MTX treatment in psoriasis is due to oxidative stress
      induced apoptosis. Psoriasis vulgaris patients (58 in number) were recruited for
      this study. Healthy volunteers (45 in number) served as control. Samples of
      psoriatic patients were collected and analyzed for total reactive oxygen species
      (ROS), malondialdehyde (MDA) levels, nitrite, nitrate levels and the activities
      of antioxidants like superoxide dismutase (SOD), catalase (CAT) and total
      antioxidant status (TAS) and also the protein expression of caspase-3, before
      (Day 0) and after (at the end of 6 and 12 weeks) MTX treatment. Our results show
      a significant increase in tissue ROS and plasma MDA after MTX treatment when
      compared with before MTX treatment in psoriasis patients (p < 0.001). The levels
      of serum nitrite and nitrate were decreased significantly after MTX treatment (p
      < 0.001). The activities of plasma SOD, TAS and serum CAT levels were decreased,
      but not significantly after 12 weeks of treatment. The expression of caspase-3
      was increased after MTX treatment. In conclusion, MTX induce apoptosis through
      oxidative stress by reducing NO and increasing caspase-3 levels. MTX-induced
      apoptosis may account for the beneficial effect of MTX treatment in psoriasis
      patients, which is characterized by acanthosis.

PMID- 23949347
TI  - Selecting Among Otolaryngology Residency Applicants to Train as Tomorrow's
      Leaders.

PMID- 23949351
TI  - The redesign of JAMA otolaryngology-head & neck surgery and the JAMA network
      journals: not just another pretty face!

PMID- 23949352
TI  - Salvage surgery for recurrent cancers of the oropharynx: comparing TORS with
      standard open surgical approaches.
AB  - IMPORTANCE: Surgical salvage may be the only viable treatment option for
      recurrent tumors of the oropharynx. To our knowledge, there have been no
      published reports directly comparing the oncologic and functional outcomes of
      patients with recurrent oropharyngeal squamous cell carcinoma (SCC) treated with
      transoral robotic-assisted surgery (TORS) with those treated with traditional
      open surgical approaches. OBJECTIVE: To compare the oncologic and functional
      outcomes of patients with recurrent oropharyngeal SCC treated with TORS with
      those treated with traditional open surgical approaches. DESIGN: Retrospective
      multi-institutional case-control study; study dates, March 2003 through October
      2011. SETTING: Four tertiary care institutions (University of Alabama at
      Birmingham; M. D. Anderson Cancer Center, Houston, Texas; Mayo Clinic, Rochester,
      Minnesota; and Henry Ford Hospital, Detroit, Michigan). PARTICIPANTS Sixty-four
      patients who underwent salvage TORS for recurrent oropharyngeal SCC were matched
      by TNM stage to 64 patients who underwent open salvage resection. INTERVENTION OR
      EXPOSURE: Salvage TORS for recurrent SCC of the oropharynx. MAIN OUTCOME AND
      MEASURES: Patient demographics, operative data, functional, and oncologic
      outcomes were recorded and compared with a similarly TNM-matched patient group
      that underwent salvage surgical resection by traditional open surgical
      approaches. RESULTS Patients treated with TORS were found to have a significantly
      lower incidence of tracheostomy use (n = 14 vs n = 50; P < .001), feeding tube
      use (n = 23 vs n = 48; P < .001), shorter overall hospital stays (3.8 days vs 8.0
      days; P < .001), decreased operative time (111 minutes vs 350 minutes; P < .001),
      less blood loss (49 mL vs 331 mL; P < .001), and significantly decreased
      incidence of positive margins (n = 6 vs n = 19; P = .007). The 2-year recurrence
      free survival rate was significantly higher in the TORS group than in the open
      approach group (74% and 43%, respectively) (P = .01). CONCLUSIONS AND RELEVANCE:
      This study demonstrates that TORS offers an alternative surgical approach to
      recurrent tumors of the oropharynx with acceptable oncologic outcomes and better
      functional outcomes than traditional open surgical approaches. This adds to the
      growing amount of clinical evidence to support the use of TORS in selected
      patients with recurrent oropharyngeal SCC as a feasible and oncologically sound
      method of treatment.

PMID- 23949353
TI  - Frailty as a predictor of morbidity and mortality in inpatient head and neck
      surgery.
AB  - IMPORTANCE: The increasing number of elderly and comorbid patients undergoing
      surgical procedures raises interest in better identifying patients at increased
      risk of morbidity and mortality, independent of age. Frailty has been identified
      as a predictor of surgical complications. OBJECTIVE: To establish the
      implications of frailty as a predictor of morbidity and mortality in inpatient
      otolaryngologic operations. DESIGN: Retrospective review of medical records.
      SETTING: National Surgical Quality Improvement Program (NSQIP) participating
      hospitals. PATIENTS: NSQIP participant use files were used to identify 6727
      inpatients who underwent operations performed by surgeons specializing in
      otolaryngology between 2005 and 2010. The study sample was 50.3% male and 10.2%
      African American, with a mean (range) age of 54.7 (16-90) years. MAIN OUTCOMES
      AND MEASURES: A previously described modified frailty index (mFI) was calculated
      on the basis of NSQIP variables. The effect of increasing frailty on morbidity
      and mortality was evaluated using univariate analysis. Multivariate logistic
      regression was used to compare mFI with age, ASA, and wound classification.
      RESULTS The mean (range) mFI was 0.07 (0-0.73). As the mFI increased from 0 (no
      frailty-associated variables) to 0.45 (5 of 11) or higher, mortality risk
      increased from 0.2% to 11.9%. The risk of Clavien-Dindo grade IV complications
      increased from 1.2% to 26.2%. The risk of all complications increased from 9.5%
      to 40.5%. All results were significant at P < .001. In a multivariate logistic
      regression model to predict mortality or serious complication, mFI became the
      dominant significant predictor. CONCLUSIONS AND RELEVANCE: The mFI is
      significantly associated with morbidity and mortality in this retrospective
      survey. Additional study with prospective analysis and external validation is
      needed. The mFI may provide an improved understanding of preoperative risk, which
      would facilitate perioperative optimization, risk stratification, and counseling
      related to outcomes.

PMID- 23949354
TI  - Elective neck dissection for no neck during salvage total laryngectomy: findings,
      complications, and oncological outcome.
AB  - IMPORTANCE: Optimum management of the clinically negative neck in the presence of
      primary site recurrence of laryngeal or hypopharyngeal cancer remains unclear.
      OBJECTIVE: To examine the incidence of occult cervical nodal metastatic disease
      in patients undergoing salvage laryngectomy with necks clinically staged as N0 at
      the time of recurrence and to define the role of elective neck dissection in this
      population with regard to risk of complications and oncologic outcomes. DESIGN:
      Retrospective study of patients treated from 1996 through 2011. SETTING: Academic
      teaching hospital. PARTICIPANTS: All patients undergoing salvage total
      laryngectomy for squamous cell carcinoma of larynx or hypopharynx after failed
      initial radiotherapy or chemoradiotherapy with radiographically N0 neck at time
      of recurrence. MAIN OUTCOMES AND MEASURES: Primary outcome measure was incidence
      of cervical nodal metastases detected by means of pathological examination of
      elective neck dissection specimens. Secondary outcome measures were incidence of
      major postoperative complications and regional cancer control. RESULTS: Forty
      five patients were included. Thirty-eight underwent elective unilateral (20) or
      bilateral (18) ND at the time of laryngectomy. Three patients (8%) had occult
      metastases (3 of 56 dissected heminecks [5%]). The incidence of major wound
      complications was significantly greater in patients undergoing bilateral ND (12
      of 18 [67%]) than in patients undergoing unilateral or no ND (8 of 27 [30%]) (P =
      .03). There was no significant difference in regional control according to
      whether bilateral, unilateral, or no ND was performed. CONCLUSIONS AND RELEVANCE:
      The incidence of occult metastatic disease in N0 necks in patients undergoing
      salvage surgery after radiotherapy is low. Neck dissection in this population
      does not seem to have a significant impact on regional cancer control. The need
      for elective ND, particularly bilateral ND, should be balanced against possible
      increased risk of morbidity in this group.

PMID- 23949356
TI  - Consistency of voice frequency and perturbation measures in children using
      cepstral analyses: a movement toward increased recording stability.
AB  - IMPORTANCE: Few studies have evaluated the pediatric voice objectively using
      acoustic measurements. Furthermore, consistency of these measurements across
      time, particularly for continuous speech, has not been evaluated. OBJECTIVES: (1)
      To evaluate normal pediatric voice frequency and perturbation using both time
      based and frequency-based acoustic measurements, and (2) to determine if
      continuous speech samples facilitate increased recording stability. DESIGN
      Prospective, longitudinal study. SETTING: Pediatric otolaryngology practice
      within a tertiary hospital. PARTICIPANTS: Forty-three children, ages 4 to 17
      years. INTERVENTION OR EXPOSURE: Sustained vowel utterances and continuous speech
      samples, which included 4 Consensus Auditory-Perceptual Evaluation of Voice (CAPE
      V) sentences and the first sentence of the "rainbow passage" ("A rainbow is a
      division of white light into many beautiful colors that takes the shape of a long
      round arch, with its path high above and its 2 ends apparently beyond the
      horizon") were obtained at 2 time points. MAIN OUTCOME AND MEASURE: Intraclass
      correlation coefficients (ICCs) were calculated to assess reliability between
      speech samples. RESULTS: Fundamental frequency of sustained vowel utterances had
      excellent reliability (ICC >= 0.94). Time-based analyses of perturbation in
      sustained vowel utterances demonstrated poor reliability (ICC < 0.40), while
      frequency-based analyses of perturbation for these utterances demonstrated good
      to excellent reliability (ICC > 0.40). Fundamental frequency of continuous speech
      sample had excellent reliability (ICC > 0.94). Frequency-based analyses of
      continuous speech samples demonstrated excellent reliability (ICC > 0.75) for all
      but 1 variable, which demonstrated good reliability (cepstral-spectral index of
      dysphonia of the all voiced sample; ICC =0.72). CONCLUSIONS AND RELEVANCE:
      Sustained vowel utterance and continuous speech samples provide consistent
      measures of fundamental frequency. Frequency-based analysis of sustained vowel
      recordings improves the reliability of perturbation measures. Continuous speech
      recordings can be obtained in children and demonstrate good to excellent
      reliability across recordings. This suggests that frequency-based analysis of
      continuous speech may be more representative of a child's voice and therefore may
      be of use in the study both of the developmental changes of the pediatric voice
      as well as the study of vocal changes pretreatment and posttreatment in children
      with voice disorders.

PMID- 23949355
TI  - Prevalence and impact of bilateral vestibular hypofunction: results from the 2008
      US National Health Interview Survey.
AB  - IMPORTANCE: Profound bilateral vestibular hypofunction (BVH) causes disabling
      oscillopsia, chronic disequilibrium, and postural instability, but little is
      known about its epidemiology and impact. OBJECTIVE: To assess prevalence and
      functional impact of BVH in the US adult population. DESIGN AND SETTING: National
      cross-sectional survey using a national database and corollary validation study.
      PATIENTS: Adult respondents to the 2008 Balance and Dizziness Supplement to the
      US National Health Interview Survey (N = 21 782). MAIN OUTCOMES AND MEASURES:
      Prevalence of BVH, socioeconomic and quality-of-life impact of BVH, and fall
      risk. Criteria for the survey-based diagnosis of BVH included all of the
      following: presence of visual blurring with head movement; unsteadiness;
      difficulty walking in darkness or unsteady surfaces and in a straight path; and
      symptoms being at least "a big problem" and present for at least 1 year, in the
      absence of other neurologic conditions or eye pathologic conditions affecting
      vision. RESULTS: Adjusted national estimates from this survey indicate the
      prevalence of BVH in 2008 was 28 per 100 000 US adults (64 046 Americans). Of the
      participants with BVH, 44% reported changing their driving habits because of
      their symptoms, 56% reported reduced participation in social activities, and 58%
      reported difficulties with activities of daily living. Respondents with BVH had a
      31-fold increase in the odds of falling in multivariate analyses compared with
      all respondents, with 25% reporting a recent fall-related injury. CONCLUSIONS AND
      RELEVANCE: As estimated by the presence of specific symptoms in a nationally
      representative survey, BVH has considerable socioeconomic and quality-of-life
      impacts and significantly increases fall risk. These data support the need for
      new therapeutic strategies for BVH, including vestibular rehabilitation and
      implantable vestibular prostheses.

PMID- 23949357
TI  - Hyoid expansion with titanium plate and screw: a human cadaveric study using
      computer-assisted airway measurement.
AB  - IMPORTANCE: Hyoid expansion with suspension can potentially increase the upper
      airway at the hypopharyngeal level, benefitting patients with sleep-related
      breathing disorder. OBJECTIVES: To document the effect of hyoid expansion using
      titanium plate and screw on retrolingual hypopharyngeal airway dimension and to
      compare the airway dimension after isolated hyoid expansion with hyoid expansion
      + hyomandibular suspension. DESIGN: Anatomical cadaveric dissection study.
      SETTING: This study was performed in a laboratory setting using human cadavers.
      INTERVENTION: This is an anatomical feasibility study of hyoid expansion using
      titanium plate and screw on 10 cadaveric human heads and necks. The hyoid bone is
      trifractured with bony cuts made just medial to the lesser cornu. The freed hyoid
      body and lateral segments are expanded and stabilized to a titanium adaptation
      plate. Computer-assisted airway measurement (CAM) was used to measure the airway
      dimension at the hypopharynx at the level of the tongue base before and after the
      hyoid expansion. The expanded hyoid bone was then suspended to the mandible, and
      the airway dimension was measured again with CAM. MAIN OUTCOMES AND MEASURES:
      Airway dimension after isolated hyoid expansion with hyoid expansion with
      hyomandibular suspension. RESULTS Hyoid expansion with titanium plate and screw
      resulted in statistical significant increase in the retrolingual hypopharyngeal
      airway space in all of the 10 human cadavers. The mean (SD) increase in
      retroglossal area was 33.4 (13.2) mm2 (P < .005) (range, 6.0-58.7 mm2). Hyoid
      expansion with hyomandibular suspension resulted in a greater degree of airway
      enlargement. The mean (SD) increase in retroglossal area was 99.4 (15.0) mm2 (P <
      .005) (range, 81.9-127.5 mm2). CONCLUSIONS AND RELEVANCE: The retrolingual
      hypopharyngeal airway space increased with hyoid expansion using titanium plate
      and screw in our human cadaveric study, measured using CAM. The degree of
      increase is further augmented with hyomandibular suspension.

PMID- 23949358
TI  - Comparison of cystic fibrosis transmembrane conductance regulator (CFTR) and
      ciliary beat frequency activation by the CFTR Modulators Genistein, VRT-532, and
      UCCF-152 in primary sinonasal epithelial cultures.
AB  - IMPORTANCE: Pharmacologic activation of mucociliary clearance (MCC) represents an
      emerging therapeutic strategy for patients with chronic rhinosinusitis, even in
      the absence of congenital mutations of the CFTR gene. Drug discovery efforts have
      identified small molecules that activate the cystic fibrosis transmembrane
      conductance regulator (CFTR), including potentiators under development for
      treatment of cystic fibrosis. OBJECTIVE: To evaluate the properties of CFTR
      modulators and their effects on ciliary beat frequency (CBF) in human sinonasal
      epithelium (HSNE). DESIGN: Primary HSNE cultures (wild type and F508del/F508del)
      were used to compare stimulation of CFTR-mediated Cl- conductance and CBF by the
      CFTR modulators genistein, VRT-532, and UCCF-152. MAIN OUTCOMES AND MEASURES:
      Increase in CFTR-dependent anion transport and CBF. RESULTS: HSNE cultures were
      analyzed using pharmacologic manipulation of ion transport (change in short
      circuit current [?ISC]) and high-speed digital imaging (CBF). Activation of CFTR
      dependent anion transport was significantly different among agonists (P < .001),
      with genistein exerting the greatest effect (mean [SD] ?ISC, genistein, 23.1
      [1.8] MUA/cm22 > VRT-532, 8.1 [1.0] MUA/cm2 > UCCF-152, 3.4 [1.4] MUA/cm2 >
      control, 0.7 [0.2] MUA/cm2; Tukey-Kramer P < .05) in the absence of forskolin.
      Genistein and UCCF-152 augmented CBF (under submerged conditions) significantly
      better (Tukey-Kramer P < .05) than cells treated with VRT-532 or dimethyl
      sulfoxide vehicle control (mean [SD] fold change over baseline, genistein, 1.63
      [0.06]; UCCF-152, 1.56 [0.06]; VRT-532, 1.38 [0.08]; control, 1.27 [0.02]).
      Activation of CBF was blunted in F508del/F508del HSNE cultures. CONCLUSIONS AND
      RELEVANCE: The degree of CBF stimulation was not dependent on the magnitude of Cl
      secretion, suggesting that different mechanisms of action may underlie MCC
      activation by these small molecule potentiators. Agents that activate both CFTR
      dependent ISC and CBF are particularly attractive as therapeutics because they
      may address 2 independent pathways that contribute to deficient MCC in chronic
      rhinosinusitis.

PMID- 23949359
TI  - Heat generation during ablation of porcine skin with erbium:YAG laser vs a novel
      picosecond infrared laser.
AB  - IMPORTANCE: Despite significant advances in surgery, most surgical tools remain
      basic. Lasers provide a means of precise surgical ablation, but their clinical
      use has remained limited because of undesired thermal, ionizing, or acoustic
      stress effects leading to tissue injury. A novel ultrafast, nonionizing,
      picosecond infrared laser (PIRL) system has recently been developed and is
      capable, in theory, of ablation with negligible thermal or acoustic stress
      effects. OBJECTIVE: To measure and compare heat generation by means of
      thermography during ablation of ex vivo porcine skin by conventional microsecond
      pulsed erbium:YAG (Er:YAG) laser and picosecond infrared laser (PIRL). DESIGN AND
      SETTING: This study was conducted in an optics laboratory and used a pretest
      posttest experimental design comparing 2 methods of laser ablation of tissue with
      each sample acting as its own control. INTERVENTION: Ex vivo porcine skin was
      ablated in a 5-mm line pattern with both Er:YAG laser and PIRL at fluence levels
      marginally above ablation threshold (2 J/cm2 and 0.6 J/cm2, respectively). MAIN
      OUTCOMES AND MEASURES: Peaks and maxima of skin temperature rises were determined
      using a thermography camera. Means of peak temperature rises were compared using
      the paired sample t test. Ablation craters were assessed by means of digital
      microscopy. RESULTS Mean peak rise in skin surface temperature for the Er:YAG
      laser and PIRL was 15.0 degrees C and 1.68 degrees C, respectively (P < .001).
      Maximum peak rise in skin surface temperature was 18.85 degrees C for the Er:YAG
      laser and 2.05 degrees C for the PIRL. Ablation craters were confirmed on digital
      microscopy. CONCLUSIONS AND RELEVANCE: Picosecond infrared laser ablation results
      in negligible heat generation, considerably less than Er:YAG laser ablation,
      which confirms the potential of this novel technology in minimizing undesirable
      thermal injury associated with lasers currently in clinical use.

PMID- 23949360
TI  - Establishment of a rabbit model of obstructive sleep apnea by paralyzing the
      genioglossus.
AB  - IMPORTANCE: This study presents an innovative method for developing a
      neuromuscular model of obstructive sleep apnea (OSA). OBJECTIVE: To establish a
      new OSA animal model simulating real upper airway conditions during sleep. DESIGN
      AND SETTING: In vivo animal study at an academic tertiary referral center.
      SUBJECTS: A total of 27 New Zealand white male rabbits were used. INTERVENTION:
      Sleep was induced by intramuscular injection of 0.3 mL/kg of tiletamine
      hydrochloride plus zolazepam hydrochloride and 0.2 mL/kg of xylazine. Upper
      airway obstruction was induced by injecting botulinum toxin type A (2.5 U in 8
      rabbits, 5.0 U in 10 rabbits, and 7.5 U in 1 rabbit) into the genioglossus. Eight
      rabbits were injected with normal saline as a control. MAIN OUTCOMES AND
      MEASURES: Drug-induced sleep was evaluated using a portable polysomnography
      device for electroencephalography, electrooculography, chin electromyography,
      nasal airflow, breathing efforts, and pulse oxymetry. Respiratory events (apneas
      or hypopneas) during sleep were evaluated using a sleep-screening tool. RESULTS:
      All the rabbits showed no apneas or hypopneas before injection of botulinum toxin
      type A. In the control rabbits injected with normal saline, apneas or hypopneas
      were not found. The respiratory events were observed in 5 of 8 rabbits injected
      with 2.5 U of botulinum toxin type A, whereas they were observed in 7 of 10
      rabbits injected with 5.0 U of botulinum toxin type A. The median (interquartile
      range) apnea hypopnea index was 9.6 (5.3-14.8) per hour and 45.6 (21.5-70.5) per
      hour in the rabbits injected with 2.5 U and 5.0 U of botulinum toxin type A,
      respectively (P = .03). CONCLUSIONS AND RELEVANCE: An animal model of OSA could
      be developed by paralyzing the genioglossus in rabbits. This model may contribute
      to identifying the pathogenesis of upper airway obstruction in OSA and to
      developing new diagnostic or treatment devices targeting specific obstruction
      sites.

PMID- 23949361
TI  - Surgical management of tumors involving the orbit.
AB  - IMPORTANCE: Surgical treatment of orbital tumors is a complex task that requires
      thorough preparation and precise planning. Since a large variety of tumors of
      different origins, anatomical extents, and histologic subtypes affect the globe,
      no "1-size-fits-all" approach can be offered. OBJECTIVE: To describe an
      integrative approach for the optimal surgical management of patients with orbital
      tumors based on a review of the literature and on our own experience at a high
      volume cancer center. EVIDENCE REVIEW: Peer-reviewed English-language literature
      and a single-center cohort of patients undergoing orbital exenteration with eye
      sparing, reconstruction, and preservation of orbital function. FINDINGS: Surgical
      treatment of orbital tumors is a complex task that requires thorough preparation
      and precise planning that would be aided by an algorithm. CONCLUSIONS AND
      RELEVANCE: We offer an algorithm that summarizes our approach toward the 2 main
      decision points of orbital surgery: extent of resection and method of
      reconstruction.

PMID- 23949362
TI  - Acute onset headache and left eye swelling.

PMID- 23949363
TI  - Nasal congestion, postnasal drip, and aural fullness.

PMID- 23949364
TI  - Nasal obstruction and anosmia.

PMID- 23949365
TI  - Submandibular swelling.

PMID- 23949366
TI  - Thyroid nodule.

PMID- 23949367
TI  - Porous material-immobilized iodo-Bodipy as an efficient photocatalyst for
      photoredox catalytic organic reaction to prepare pyrrolo[2,1-a]isoquinoline.
AB  - Iodo-Bodipy immobilized on porous silica was used as an efficient recyclable
      photocatalyst for photoredox catalytic tandem oxidation-[3+2] cycloaddition
      reactions of tetrahydroisoquinoline with N-phenylmaleimides to prepare
      pyrrolo[2,1-a]isoquinoline. 

PMID- 23949368
TI  - An ecological perspective on marine reserves in prey-predator dynamics.
AB  - This paper describes a prey-predator type fishery model with prey dispersal in a
      two-patch environment, one of which is a free fishing zone and other is a
      protected zone. The existence of possible steady states, along with their local
      stability, is discussed. A geometric approach is used to derive the sufficient
      conditions for global stability of the system at the positive equilibrium.
      Relative size of the reserve is considered as control in order to study optimal
      sustainable yield policy. Subsequently, the optimal system is derived and then
      solved numerically using an iterative method with Runge-Kutta fourth-order
      scheme. Numerical simulations are carried out to illustrate the importance of
      marine reserve in fisheries management. It is noted that the marine protected
      area enables us to protect and restore multi-species ecosystem. The results
      illustrate that dynamics of the system is extremely interesting if simultaneous
      effects of a regulatory mechanism like marine reserve is coupled with harvesting
      effort. It is observed that the migration of the resource, from protected area to
      unprotected area and vice versa, is playing an important role towards the
      standing stock assessment in both the areas which ultimately control the
      harvesting efficiency and enhance the fishing stock up to some extent. 

PMID- 23949369
TI  - Effects of adopting the new global lung function initiative 2012 reference
      equations on the interpretation of spirometry.
AB  - BACKGROUND: The recently generated spirometry reference equations from the Global
      Lung Function Initiative (GLI2012) provide a long-awaited opportunity for the
      adoption of a globally applicable set of normal reference values. OBJECTIVE: The
      aim of this study was to document the likely interpretative effects of changing
      from commonly used current spirometry reference equations to the GLI2012
      equations on interpretation of test results in a clinical spirometry dataset.
      METHODS: Spirometry results from 2,400 patients equally distributed over the age
      range of 5-85 years were obtained from clinical pulmonary function laboratories
      at three public hospitals. The frequency of obstruction [FEV1/FVC below the lower
      limits of normal (LLN)] and spirometric restriction (FVC below the LLN) was
      assessed using the GLI2012, the National Health and Nutrition Assessment Survey
      (NHANES III), the European Community of Steel and Coal (ECSC) and the Stanojevic
      all-ages reference equations. RESULTS: The rates of obstruction (range 20.0
      28.5%) and spirometric restriction (range 14.2-25.8%) were similar across the
      four sets of reference equations. The highest level of agreement with the new
      GLI2012 equations was seen with the NHANES III equations (97.6% for obstruction
      and 93.6% for spirometric restriction) and the lowest with those from the ECSC
      (96.0 for obstruction and 92.0% for restriction). These data can be used to
      estimate likely diagnostic spirometry interpretation effects in the clinical
      setting when switching to GLI2012 spirometry reference data. CONCLUSIONS: We have
      found the effects on interpretation of changing to GLI2012 reference data to be
      minimal when changing from NHANES III and most significant when changing from
      ECSC reference data.

PMID- 23949370
TI  - Clinical assessment of amyloid imaging in Alzheimer's disease: a systematic
      review of the literature.
AB  - BACKGROUND/AIMS: Healthcare systems face an increased prevalence of Alzheimer's
      disease and increasing costs. The use of molecular biomarkers and imaging could
      offer an effective solution for these issues. The objective of this study was to
      assess amyloid imaging regarding clinical utility and impact. METHODS: A
      literature search was performed in several databases, searching articles between
      2008 and January 2013 following the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses (PRISMA) guidelines. The results are reported according
      to the clinical correlates of amyloid imaging. RESULTS: Thirty-three studies were
      included in the final analysis. Five studies evaluated amyloid imaging for
      diagnosis. Nine studies assessed the prognostic value. Twenty-two studies
      provided correlations to cognitive measures. Amyloid imaging provides a high
      reliability in diagnosis and prognosis, but cognitive measures only showed weak
      correlations. CONCLUSION: The evidence clearly indicated that amyloid imaging has
      not arrived yet in clinical practice. However, it can provide substantial
      benefits in special aspects of diagnostic accuracy and for a diagnosis up to 10
      years before clinical diagnosis. This can be a base for early preventive
      treatment strategies such as anti-amyloid therapy. In this context, amyloid
      imaging is crucial to understand the early pathologic process in Alzheimer's
      disease.

PMID- 23949371
TI  - Hv-CBF2A overexpression in barley accelerates COR gene transcript accumulation
      and acquisition of freezing tolerance during cold acclimation.
AB  - C-Repeat Binding Factors (CBFs) are DNA-binding transcriptional activators of
      gene pathways imparting freezing tolerance. Poaceae contain three CBF
      subfamilies, two of which, HvCBF3/CBFIII and HvCBF4/CBFIV, are unique to this
      taxon. To gain mechanistic insight into HvCBF4/CBFIV CBFs we overexpressed Hv
      CBF2A in spring barley (Hordeum vulgare) cultivar 'Golden Promise'. The Hv-CBF2A
      overexpressing lines exhibited stunted growth, poor yield, and greater freezing
      tolerance compared to non-transformed 'Golden Promise'. Differences in freezing
      tolerance were apparent only upon cold acclimation. During cold acclimation
      freezing tolerance of the Hv-CBF2A overexpressing lines increased more rapidly
      than that of 'Golden Promise' and paralleled the freezing tolerance of the winter
      hardy barley 'Dicktoo'. Transcript levels of candidate CBF target genes, COR14B
      and DHN5 were increased in the overexpressor lines at warm temperatures, and at
      cold temperatures they accumulated to much higher levels in the Hv-CBF2A
      overexpressors than in 'Golden Promise'. Hv-CBF2A overexpression also increased
      transcript levels of other CBF genes at FROST RESISTANCE-H2-H2 (FR-H2) possessing
      CRT/DRE sites in their upstream regions, the most notable of which was CBF12.
      CBF12 transcript levels exhibited a relatively constant incremental increase
      above levels in 'Golden Promise' both at warm and cold. These data indicate that
      Hv-CBF2A activates target genes at warm temperatures and that transcript
      accumulation for some of these targets is greatly enhanced by cold temperatures. 

PMID- 23949372
TI  - Revisiting physical examination: Abadie's sign and Achilles intratendinous
      changes in subjects with diabetes.
AB  - OBJECTIVE: The aim of this study was to evaluate whether or not the positivity of
      Abadie's sign could be an indicator of asymptomatic Achilles intratendinous
      changes. SUBJECTS AND METHODS: A total of 18 patients (36 tendons) suffering from
      diabetes, with at least 1 Achilles tendon positive to Abadie's sign, were
      compared to matched subjects with diabetes bilaterally negative to Abadie's sign.
      Anthropometric measures and the Toronto Clinical Neuropathy Score were
      registered. Echotexture was evaluated and degenerative features classified as
      absent, mild, moderate and severe. The frequencies of structural abnormalities,
      according to both Abadie's sign and the Toronto Clinical Neuropathy Score, were
      determined. RESULTS: In the first group 26 out of 36 tendons (72.2%) showed
      positive Abadie's sign and a significantly higher frequency of moderate and
      severe (65.3%) structural abnormalities compared to Achilles tendons with
      negative sign (4.3%; p < 0.0001). This frequency was similar to that observed in
      the subjects with the highest Toronto Clinical Neuropathy Score (64.2%).
      CONCLUSIONS: This study showed that Abadie's sign was a useful tool for assisting
      in the diagnosis of asymptomatic Achilles intratendinous changes, which, when
      detected early, could help prevent unexpected tendon rupture. The concordance
      between Abadie's sign and Achilles sonographic abnormalities needs to be
      evaluated in a larger sample to consider it useful for practical purposes.

PMID- 23949373
TI  - [Psychiatrists in national socialism: examples of civil courage].

PMID- 23949374
TI  - Weak link of tendon-bone healing and a control experiment to promote healing.
AB  - OBJECTIVE: This study aims to observe the mechanical weak point and histological
      features of tendon-bone interface after anterior cruciate ligament reconstructive
      surgery and to explore the tendon-bone healing effects of the platelet-rich gel
      (PRG) + deproteinized bone (DPB) compound. METHODS: A total of 48 New Zealand
      white rabbits were randomly divided into normal group, model (without embedding),
      experimental (embedded with the PRG + DPB compound), and control (embedded with
      DPB) groups. The rabbits were executed at 2, 4, 8, and 12 weeks after the
      operation. Then, micro-computed tomography scan and uniaxial tensile test were
      conducted. The fractured specimens were subjected to histological observation.
      RESULTS: At 4, 8, and 12 weeks after the operation, the bone density of the
      tendon-bone bound section of the experimental group was higher than that of the
      other groups (P < 0.05). At 4 and 8 weeks, the maximum tensile load of the
      experimental group was obviously higher than that of the control and model groups
      (P < 0.05). Histological observation indicated that the tendon-bone interface in
      the experimental group had more cartilage and bone tissue growing toward the
      internal tendon, but the fracture layer mainly occurred in the non-ankylosed
      part. CONCLUSION: The mechanical weak point of the early tendon-bone interface
      was in the immature fibrous tissue. The PRG + DPB compound can effectively
      trigger tendon-bone healing by promoting the maturation and ossification of the
      tendon-bone tissue. This compound improved the tensile strength of the healing
      interface and reduced bone tunnel enlargement.

PMID- 23949375
TI  - Touching on translation.
AB  - During the last decade, the idea of a "translational" approach has become
      commonplace within the field of neuroscience. Despite the rapid adaptation of
      this theoretical framework, few examples of hypothesis-driven translation start
      with a pre-clinical finding and end with a positive clinical result and no
      examples of a novel medication have been developed in this way for the treatment
      of cognition-related disorders. Whereas instances of successful translation
      exist, most of these are the result of post-hoc hypothesis testing, rather than a
      priori hypothesis creation. Indeed, part of this disconnection between pre
      clinical and clinical results has been driven by paradigms used at both the pre
      clinical level (measurement of behaviors that might not be relevant to a patient
      population) and the clinical level (use of test batteries that cannot be modeled
      in a pre-clinical environment). However, automated cognition batteries that
      require responses to stimuli displayed upon a video monitor are decreasing the
      distance between pre-clinical and clinical behavioral studies. In the last 5
      years, numerous papers have been published demonstrating that cognitive functions
      can be measured in a similar manner in the rodent as in a clinical setting via
      touch-screen-equipped operant boxes. Here, we argue that the touch-screen
      approach has the potential of being a powerful tool for the translation of pre
      clinical hypotheses into positive clinical findings.

PMID- 23949376
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- 23949377
TI  - Unexplained severe Coombs-negative hemolytic anemia during treatment of
      refractory chronic lymphocytic leukemia with alemtuzumab.

PMID- 23949378
TI  - In situ and real-time monitoring of mechanochemical milling reactions using
      synchrotron X-ray diffraction.
AB  - We describe the only currently available protocol for in situ, real-time
      monitoring of mechanochemical reactions and intermediates by X-ray powder
      diffraction. Although mechanochemical reactions (inducing transformations by
      mechanical forces such as grinding and milling) are normally performed in
      commercially available milling assemblies, such equipment does not permit direct
      reaction monitoring. We now describe the design and in-house modification of
      milling equipment that allows the reaction jars of the operating mill to be
      placed in the path of a high-energy (~90 keV) synchrotron X-ray beam while the
      reaction is taking place. Resulting data are analyzed using conventional
      software, such as TOPAS. Reaction intermediates and products are identified using
      the Cambridge Structural Database or Inorganic Crystal Structure Database.
      Reactions are analyzed by fitting the time-resolved diffractograms using
      structureless Pawley refinement for crystalline phases that are not fully
      structurally characterized (such as porous frameworks with disordered guests), or
      the Rietveld method for solids with fully determined crystal structures (metal
      oxides, coordination polymers). 

PMID- 23949379
TI  - Analysis of the proteolysis of bioactive peptides using a peptidomics approach.
AB  - Identifying the peptidases that inactivate bioactive peptides (e.g., peptide
      hormones and neuropeptides) in mammals is an important unmet challenge. This
      protocol describes a recent approach that uses liquid chromatography-mass
      spectrometry (LC-MS) peptidomics to identify endogenous cleavage sites of a
      bioactive peptide; it also addresses the subsequent biochemical purification of a
      candidate peptidase on the basis of these cleavage sites and the validation of
      the candidate peptidase's role in the physiological regulation of the bioactive
      peptide by examining a peptidase-knockout mouse. We highlight the successful
      application of this protocol in the discovery that insulin-degrading enzyme (IDE)
      regulates physiological calcitonin gene-related peptide (CGRP) levels, and we
      detail the key stages and steps in this approach. This protocol requires 7 d of
      work; however, the total time for this protocol is highly variable because of its
      dependence on the availability of biological reagents such as purified enzymes
      and knockout mice. The protocol is valuable because it expedites the
      characterization of mammalian peptidases, such as IDE, which in certain instances
      can be used to develop novel therapeutics. 

PMID- 23949380
TI  - Single-molecule mRNA detection and counting in mammalian tissue.
AB  - We present a protocol for visualizing and quantifying single mRNA molecules in
      mammalian (mouse and human) tissues. In the approach described here, sets of
      about 50 short oligonucleotides, each labeled with a single fluorophore, are
      hybridized to target mRNAs in tissue sections. Each set binds to a single mRNA
      molecule and can be detected by fluorescence microscopy as a diffraction-limited
      spot. Tissue architecture is then assessed by counterstaining the sections with
      DNA dye (DAPI), and cell borders can be visualized with a dye-coupled antibody.
      Spots are detected automatically with custom-made software, which we make freely
      available. The mRNA molecules thus detected are assigned to single cells within a
      tissue semiautomatically by using a graphical user interface developed in our
      laboratory. In this protocol, we describe an example of quantitative analysis of
      mRNA levels and localization in mouse small intestine. The procedure (from tissue
      dissection to obtaining data sets) takes 3 d. Data analysis will require an
      additional 3-7 d, depending on the type of analysis. 

PMID- 23949382
TI  - The Severity of ICU-Acquired Pneumonia.
AB  - Much controversy exists about pneumonia in intensive care-especially, ventilator
      associated pneumonia (VAP)-about its diagnosis and its attributable mortality. A
      better consensus exists about its prevention and its treatment. VAP occurs in
      already critically ill patients, and the relationship between preexisting organ
      dysfunction or failures and the severity of VAP has been recently highlighted.
      The role of the underlying disease should be considered as dominant, and this
      fact explains the paradox that exists between the high mortality of VAP and the
      relative minor effect of prevention measures on mortality. 

PMID- 23949381
TI  - The motor system resonates to the distal goal of observed actions: testing the
      inverse pliers paradigm in an ecological setting.
AB  - Does motor mirroring in humans reflect the observed movements or the goal of the
      observed motor acts? Tools that dissociate the agent/object dynamics from the
      movements of the body parts used to operate them provide a model for testing
      resonance to both movements and goals. Here, we describe the temporal
      relationship of the observer's motor excitability, assessed with transcranial
      magnetic stimulation (TMS), with the observed goal-directed tool actions, in an
      ecological setting. Motor-evoked potentials (MEPs) to TMS were recorded from the
      opponens pollicis (OP, thumb flexor) and the extensor indicis proprius (EIP,
      index extensor) muscles of participants while they observed a person moving
      several small objects with a pair of normal pliers (closed by finger flexion) or
      reverse pliers (opened by finger flexion). The MEPs were a significant predictor
      of the pliers' kinematics that occurred in a variable time interval between -400
      and +300 ms from TMS. Whatever pliers' type was being observed, OP MEPs
      correlated positively and EIP MEPs correlated negatively with the velocity of
      pliers' tips closure. This datum was confirmed both at individual and at a group
      level. Motor simulation can be demonstrated in single observers in a "real-life"
      ecological setting. The relation of motor resonance to the tool type shows that
      the observer's motor system codes the distal goal of the observed acts (i.e.,
      grasping and releasing objects) in terms of its own motor vocabulary,
      irrespective of the actual finger movements that were performed by the observed
      actor.

PMID- 23949384
TI  - One bacterial effector with two distinct catalytic activities by different
      strains.

PMID- 23949383
TI  - Initial characterization of histone H3 serine 10 O-acetylation.
AB  - In eukaryotic organisms, histone posttranslational modifications (PTMs) are
      indispensable for their role in maintaining cellular physiology, often through
      their mediation of chromatin-related processes such as transcription. Targeted
      investigations of this ever expanding network of chemical moieties continue to
      reveal genetic, biochemical, and cellular nuances of this complex landscape. In
      this study, we present our findings on a novel class of histone PTMs: Serine,
      Threonine, and Tyrosine O-acetylation. We have combined highly sensitive nano-LC
      MS/MS experiments and immunodetection assays to identify and validate these
      unique marks found only on histone H3. Mass spectrometry experiments have
      determined that several of these O-acetylation marks are conserved in many
      species, ranging from yeast to human. Additionally, our investigations reveal
      that histone H3 serine 10 acetylation (H3S10ac) is potentially linked to cell
      cycle progression and cellular pluripotency. Here, we provide a glimpse into the
      functional implications of this H3-specific histone mark, which may be of high
      value for further studies of chromatin. 

PMID- 23949385
TI  - DNGR-ing the dendritic cell lineage.

PMID- 23949386
TI  - Interleukin-1beta plays key roles in LPA-induced amplification of LPA production
      in neuropathic pain model.
AB  - Lysophosphatidic acid (LPA) is a bioactive lipid mediator that exerts a wide
      range of biological actions. In recent decades, LPA has been demonstrated as an
      important initiator of neuropathic pain based on the mechanisms of LPA-induced
      feed-forward LPA amplification. In this study, we examined the possible
      involvement of interleukin (IL)-1beta in such LPA production. Intrathecal (i.t.)
      LPA injection rapidly increased the expression of IL-1beta mRNA in the spinal
      dorsal horn as early as 0.5 h after injection, and the level reached peak at 2 h.
      Through a developed quantitative mass spectrometry for detecting LPA species, the
      elevated levels of 18:1, 16:0, and 18:0 LPA in the spinal dorsal horn were
      observed at 3 h after 18:1 LPA injection and this elevation was completely
      blocked by the pretreatment of IL-1beta-neutralizing antibody. Moreover, enzyme
      assay experiments showed that LPA (i.t.) significantly activated calcium
      independent phospholipase A2 (iPLA2) and cytosolic phospholipase A2 (cPLA2) in
      the spinal dorsal horn at 1 and 2 h, respectively, and these biochemical changes
      were also significantly inhibited by IL-1beta-neutralizing antibody. Similarly,
      IL-1beta-neutralizing antibody reversed LPA-induced neuropathic pain-like
      behavior. These findings suggest that the early release of IL-1beta is involved
      in LPA-induced amplification of LPA production, which underlies the initial
      mechanisms of LPA-induced neuropathic pain.

PMID- 23949387
TI  - An ICT-based fluorescent switch-on probe for hydrogen sulfide in living cells.
AB  - An ICT-based fluorescent turn-on probe for hydrogen sulfide with high selectivity
      has been designed and synthesized. It exhibits up to 62-fold switch-on response
      toward H2S at given concentrations and can detect H2S in living cells with high
      sensitivity. 

PMID- 23949388
TI  - Surgical treatment and prevention of recurrence of urethral calculi associated
      with hairballs after urethroplasty.
AB  - OBJECTIVES: To evaluate technical aspects and outcome of preventing
      urethrocutaneous fistula and calculi recurrence in surgical treatment of urethral
      calculi associated with hairballs after urethroplasty. PATIENTS AND METHODS:
      Sixteen patients who had urethral calculi associated with hairballs after
      urethroplasty underwent urethrolithotomy and trimming and epilation of the
      neourethra. While operating, we made a staggered incision of the skin and
      urethra, carefully sutured the urethral incision, and covered it by well
      vascularized tissue. A tube-in-tube stent method was performed on the latter 12
      patients for better drainage of the exudates that accumulated in the urethra.
      RESULTS: All calculi were successfully removed. Surgical site infection occurred
      in the last one of the former 4 patients and resulted in an urethrocutaneous
      fistula. There were no other complications. All patients were followed up for 2-7
      years; no urethral stenosis or recurrence of calculi was observed, and remarkable
      reduction of urethral hair was obtained. CONCLUSIONS: Urethrolithotomy and
      trimming and epilation of the neourethra seem to be appropriate treatments for
      urethral calculi associated with hairballs after urethroplasty. Full attention
      should be paid to fistula prevention.

PMID- 23949390
TI  - What's new in Shock? September 2013.

PMID- 23949389
TI  - Putative miRNAs for the diagnosis of dyslexia, dyspraxia, and specific language
      impairment.
AB  - Disorders of human communication abilities can be classified into speech and
      language disorders. Speech disorders (e.g., dyspraxia) affect the sound
      generation and sequencing, while language disorders (e.g., dyslexia and specific
      language impairment, or SLI) are deficits in the encoding and decoding of
      language according to its rules (reading, spelling, grammar). The diagnosis of
      such disorders is often complicated, especially when a patient presents more than
      one disorder at the same time. The present review focuses on these challenges. We
      have combined data available from the literature with an in silico approach in an
      attempt to identify putative miRNAs that may have a key role in dyspraxia,
      dyslexia and SLI. We suggest the use of new miRNAs, which could have an important
      impact on the three diseases. Further, we relate those miRNAs to the axon
      guidance pathway and discuss possible interactions and the role of likely
      deregulated proteins. In addition, we describe potential differences in
      expressional deregulation and its role in the improvement of diagnosis. We
      encourage experimental investigations to test the data obtained in silico. 

PMID- 23949391
TI  - Polymyxin B-immobilized fiber column hemoperfusion therapy for septic shock.

PMID- 23949392
TI  - Reply: To PMID 21654557.

PMID- 23949393
TI  - Outcomes in critically ill cancer patients with septic shock of pulmonary origin.
      Shock 39: 250-254, 2013.

PMID- 23949394
TI  - Electrically-induced heat amputation of the hand in a case of fatal electric
      shock caused by a faulty table lamp.

PMID- 23949395
TI  - Microcirculation in the intensive care unit.

PMID- 23949396
TI  - From "infection in intensive care" to "intensive care in infection": intensive
      care specialists' perspective of tropical medicine.

PMID- 23949397
TI  - Guidelines for potential multiple organ donors (adult): part I. Overview and
      hemodynamic support.
AB  - There is a relative shortage of appropriate organs available for transplantation.
      The appropriate diagnosis of brain death, a suitable family approach and the
      maintenance of the deceased donor are fundamental in addressing this issue. The
      intensive care physician plays a key role in the maintenance of the deceased
      donor, thereby reducing losses and increasing the number of successful
      transplants. 

PMID- 23949398
TI  - Guidelines for potential multiple organ donors (adult): part II. Mechanical
      ventilation, endocrine metabolic management, hematological and infectious
      aspects.
AB  - The role of intensive care specialists in the maintenance of deceased potential
      donors is not restricted to hemodynamics. Appropriate endocrine-metabolic
      management is fundamental to maintaining energy support and hydroelectrolytic
      control, which cooperate for hemodynamic stability. Hematological changes are
      also important, especially considering the issues caused by inappropriate
      transfusions. In addition, this article discusses the role of appropriate
      protective ventilation to prevent inflammatory responses and to provide more
      transplantable lungs. Finally, judicious assessment of infections and antibiotic
      therapy is discussed. 

PMID- 23949399
TI  - Hemodynamic and perfusion variables during experimental septic shock treated with
      goal-directed fluid resuscitation.
AB  - OBJECTIVES: Although fluid resuscitation guided by central venous oxygen
      saturation (SvcO2) is currently considered the gold standard in sepsis therapy,
      few studies have described hemodynamic and perfusion parameters during this
      procedure. This study aims to describe these parameters during septic shock
      without resuscitation and after 12 hours of goal-directed resuscitation. METHODS:
      Thirteen anesthetized pigs (35-45 kg) had peritonitis caused by fecal inoculation
      (0.75 g/kg). After developing persistent hypotension, both groups were given
      antibiotics and randomized either to the control group (n=7) or the experimental
      group (n=6). In the control group, hemodynamic control was optimized to maintain
      a central venous pressure of 8-12 mmHg, a urinary output above 0.5 mL/kg/hour and
      a mean arterial blood pressure above 65 mmHg. The experimental group received the
      above target therapy in addition to maintaining a SvO2 above 65%. The
      interventions included lactated Ringer's solution and norepinephrine for both
      groups and dobutamine in the SvO2 group. The animals were treated for 12 hours or
      until death. RESULTS: Untreated sepsis was associated with significant reductions
      in SvO2, PvO2, cardiac output and central venous pressure in addition to
      increased arteriovenous oxygen saturation and veno-arterial CO2 differences.
      Following resuscitation, these parameters were corrected in both groups. Goal
      directed resuscitation was associated with a better hemodynamic profile,
      characterized by higher SvO2, cardiac output and central venous pressure.
      CONCLUSIONS: Non-resuscitated sepsis showed a hemodynamic profile suggesting
      hypovolemia, with worsened perfusion and hemodynamics, which is reversed upon
      fluid resuscitation. Goal-directed resuscitation is associated with significantly
      improved hemodynamic and perfusion parameters.

PMID- 23949400
TI  - The impact of positive end-expiratory pressure on cerebral perfusion pressure in
      adult patients with hemorrhagic stroke.
AB  - Positive intrathoracic pressure may cause hemodynamic changes, which can be
      transmitted to the cranial compartment, changing intracranial pressure and
      cerebral perfusion pressure. This can be increased when high positive end
      expiratory pressure values are used. OBJECTIVE: To measure the impact of
      different positive end-expiratory pressure levels on intracranial pressure,
      cerebral perfusion pressure and mean blood pressure. METHOD: This study was
      conducted in a neurological intensive care unit and included 25 adult hemorrhagic
      stroke patients who were mechanically ventilated on airway pressure control mode.
      Patients were subjected to various positive end-expiratory values ranging between
      0 and 14 cmH2O. The order of these values were randomized, and the variables were
      assessed five minutes after each new positive end-expiratory pressure level was
      initiated. RESULTS: Incremental positive end-expiratory pressures led to
      increased intracranial pressure (p < 0.001), however, no statistically
      significant changes were observed in mean blood pressure or cerebral perfusion
      pressure. CONCLUSION: In this population of patients with hemorrhagic stroke,
      positive end-expiratory pressure values up to 14 cmH2O did not alter cerebral
      perfusion pressure or mean blood pressure. Increased intracranial pressures were
      noted, although these elevations were not clinically significant.

PMID- 23949401
TI  - Gender and mortality in sepsis: do sex hormones impact the outcome?
AB  - OBJECTIVE: Comparative assessment of the mortality rates of two septic patients'
      ages and/or gender subgroups, admitted to the intensive care unit of a university
      hospital. METHODS: From December 2005 to April 2008, from a total of 628
      patients, 133 were admitted to the intensive care unit with sepsis and included
      into two age subgroups: (G1) 14 - 40 years old and (G2) more than 50 years old.
      Patients aged between 41 and 50 years old (n = 8) were excluded. Demographic
      data, prognostic indicators (APACHE II score, organ dysfunction and circulatory
      shock) and outcome (mortality) were analyzed. RESULTS: Of the G1 patients (n =
      44), 27 were female (61.4%), and in G2 (n = 81), 40 were female (49.4%). For both
      groups, mean APACHE II scores, multi-organ dysfunction and progression to
      circulatory shock rates were not significantly different between female and male
      patients. For G1, overall mortality rate was lower in female than in male
      patients (P = 0.04), while for G2, the opposite trend was observed. CONCLUSIONS:
      In this sample, reproductive age female patients younger than 40 years old showed
      lower mortality rates compared with age-matched male patients; for patients older
      than 50 years old, male patients had lower mortality rates than female patients.

PMID- 23949402
TI  - Postoperative complications of surgically treated ascending aortic dissection.
AB  - OBJECTIVES: Ascending aortic dissection has a poor prognosis if it is not
      promptly corrected surgically. Even with surgical correction, postoperative
      management is feared because of its complicated course. Our aim was to describe
      the incidence of postoperative complications and identify the 1 and 6-month
      mortality rate of our ascending aortic dissection surgical cohort. Secondarily, a
      comparison was made between ascending aortic dissection patients and paired
      matched patients who received urgent coronary artery bypass graft surgery.
      METHODS: A retrospective analysis of a prospectively-collected database from
      February 2005 through June 2008 revealed 12 ascending aortic dissection and 10
      elective ascending aortic aneurysm repair patients. These patients were analyzed
      for demographic and perioperative characteristics. Ascending aortic dissection
      patients were compared to paired-matched coronary artery bypass graft surgery
      patients according to age (+/- 3 years), gender, elective/urgent procedure and
      surgical team. The main outcome was in-hospital morbidity, defined by
      postoperative complications, intensive care unit admission and hospital length of
      stay. RESULTS: Twenty-two patients received operations to correct ascending
      aortic dissections and ascending aortic aneurysms, while 246 patients received
      coronary artery bypass graft surgeries. Ascending aortic dissection patients were
      notably similar to ascending aortic aneurysm brackets, except for longer
      mechanical ventilation times and lengths of stay in the hospital. After matching
      coronary artery bypass graft surgery patients to an ascending aortic dissection
      group, the following significantly worse results were found for the Aorta group:
      higher incidence of postoperative complications (91% vs. 45%, p=0.03), and longer
      hospital length of stay (19 [11-41] vs. 12.5 [8.5-13] days, p=0.05). No
      difference in mortality was found at the 1-month (8.3%) or 6-month (16.6%)
      postoperative care date. CONCLUSION: Ascending aortic dissection correction is
      associated with an increased incidence of postoperative complications and an
      increased hospital length of stay, but 1 and 6-month mortality is similar to that
      of paired-matched coronary artery bypass graft surgery patients.

PMID- 23949403
TI  - Complications and hospital length of stay in coronary artery bypass graft surgery
      in public hospitals in Rio de Janeiro.
AB  - OBJECTIVE: To evaluate associations between post-operative complications in
      patients who survive surgery and in-hospital deaths and lengths of hospital stays
      of patients who undergo coronary artery bypass graft surgery METHODS: Patients
      who underwent coronary artery bypass graft surgery and survived the operating
      theater were randomly selected. Information on complications and hospital lengths
      of stay until hospital discharge or death were retrospectively collected based on
      medical records and declarations of death. These aspects were estimated according
      to the presence of complications, frequency of complications, mortality, relative
      risk and attributable population risk. Mean hospital lengths of stay were
      compared using Wald's statistics. RESULTS: Medical records indicating deaths in
      the operating theater were excluded, and 86.9% of the included records reported
      complications; the greatest loss of information (43.9%) was related to kidney
      failure. Hyperglycemia was estimated as the most frequent complication (74.6%),
      with an attributable risk of 31.6%. The population's attributable risks were
      greater than 60% for low cardiac output (77.0%), kidney failure (64.3%) and
      cardiorespiratory failure (60.4%). Twelve different situations were identified
      for paired combinations of significant differences between average post-operative
      hospitalization times and complications, according to the outcome of discharge or
      death. CONCLUSION: Several complications were identified during the postoperative
      period of coronary artery bypass graft surgery, with different frequencies and
      impacts on mortality. Control of the myocardium at the risk of ischemia,
      hemodynamic stabilization and volume replacement strategies may be effective for
      controlling mortality rates and shortening hospital lengths of stay.

PMID- 23949404
TI  - Acute kidney injury in intensive care unit patients: a prospective study on
      incidence, risk factors and.
AB  - OBJECTIVE: To compare the clinical features and outcomes of patients with and
      without acute kidney injury in an intensive care unit of a tertiary university
      hospital and to identify acute kidney injury and mortality risk factors. METHODS:
      This was a prospective observational study of a cohort including 564 patients
      followed during their stay in the intensive care unit of Hospital das Clinicas da
      Faculdade de Medicina de Botucatu (Botucatu, Sao Paulo, Brazil) between May 2008
      and May 2010. Patients were allocated to two different groups: with (G1) and
      without (G2) acute kidney injury. RESULTS: The incidence of acute kidney injury
      was 25.5%. The groups were different with respect to the reason for admission to
      the intensive care unit (sepsis, G1: 41.6% versus G2: 24.1%; P < 0.0001;
      neurosurgery, postoperative G1: 13.8% versus G2: 38.1%; P < 0.0001); age (G1:
      56.8 +/- 15.9 vs. G2: 49.8 +/- 17.8 years; P < 0.0001); Acute Physiological
      Chronic Health Evaluation (APACHE) II score (G1: 21.9 +/- 6.9 versus G2: 14.1 +/-
      4.6; P < 0.0001); use of mechanical ventilation (G1: 89.2% vs. G2: 69.1%; P <
      0.0001) and use of vasoactive drugs (G1: 78.3% vs. G2: 56.1%; P < 0.0001). Higher
      rates of diabetes mellitus, congestive heart failure, chronic renal disease and
      use of non-steroidal anti-inflammatory drugs were more frequent in acute kidney
      injury patients (28.2% vs. 19.7%, P = 0.03; 23.6 vs. 11.6%, P = 0.0002; 21.5% vs.
      11.5%, P < 0.0001 and 23.5% vs. 71.%, P < 0.0001, for G1 versus G2,
      respectively). Length of hospital stay and mortality were also higher for acute
      kidney injury patients (G1: 6.6 +/- 2.7 days versus G2: 12.9 +/-5.6 days, P <
      0.0001 and G1: 62.5% versus G2: 16.4%, P < 0.0001). Multivariate analysis
      identified the following as risk factors for acute kidney injury: age above 55
      years, APACHE II score above 16, baseline creatinine above 1.2 and use of non
      steroidal anti-inflammatory drugs (odds ratio (OR) = 1.36, 95% confidence
      interval (95%CI): 1.22 - 1.85; OR = 1.2, 95%CI: 1.11 - 1.33; OR = 5.2, 95%CI: 2.3
      - 11.6 and OR = 2.15, 95%CI: 1.1 - 4.2, respectively). Acute kidney injury was
      independently associated with longer hospital stay and increased mortality (OR =
      1.18, 95%CI: 1.05 - 1.26 and OR = 1.24, 95%CI: 1.09 - 1.99, respectively).
      Analysis of the survival curve 30 days after admission showed 83.3% mortality for
      acute kidney injury patients and 45.2% for non-acute kidney injury patients (P <
      0.0001). CONCLUSION: The incidence of acute kidney injury was high in this
      intensive care unit; the independent risk factors associated with acute kidney
      injury were age > 55 years, APACHE II > 16, baseline serum creatinine > 1.2 and
      use of non-steroidal anti-inflammatory drugs. Acute kidney injury is an
      independent risk factor for longer intensive care unit stay and mortality.

PMID- 23949405
TI  - Effectiveness of a noise control program in a neonatal intensive care unit.
AB  - PURPOSE: To evaluate the effectiveness of a noise control program in the Neonatal
      Intensive Care Unit of the Hospital Universitario Santa Maria (NICU-HUSM) in
      Santa Maria, Rio Grande do Sul, Brazil. METHODS: NICU-HUSM professionals were
      initially contacted through informal interviews during the morning, afternoon and
      night shifts. Leaflets were delivered and posters were installed to raise
      awareness of the harmful effects of noise on neonates and professionals and to
      suggest behavioral changes to reduce noise levels. The suggestions included
      avoiding loud talking, careful handling of the incubator doors and keeping mobile
      phones on silent mode. One month later, questionnaires were used to assess
      behavioral changes since the first contact. RESULTS: Most of the professionals
      rated the NICU-HUSM noise level as moderate. Overall, 71.4% of the respondents
      acknowledged that their behaviors were noisy. The entire sample reported
      believing that the unit noise levels could be reduced by speaking lower, reacting
      more quickly to alarms and handling furniture more carefully. The NICU
      professionals reported adopting these behaviors. CONCLUSION: This noise control
      program was considered successful because the professionals became aware of the
      level of noise and adopted behavioral changes to avoid generating unnecessary
      noise.

PMID- 23949406
TI  - Intermittent heparin is not effective at preventing the occlusion of peripherally
      inserted central venous catheters in preterm and term neonates.
AB  - OBJECTIVE: To evaluate the effectiveness of intermittent 10 U/mL heparin flushes
      in reducing the occlusion of peripherally inserted central catheters in neonates.
      METHODS: In this randomized, open-label, prospective, controlled study, neonates
      were allocated either to receive 0.5 mL flushes of heparin (Group 1: n = 64) or
      saline (Group 2: n = 69) every 4 hours. Actions were taken to restore patency by
      using negative pressure (3-way stopcock method) in cases of occlusion. RESULTS: A
      total of 133 neonates were included. No significant intergroup difference was
      observed in the number of new occlusions (26 in Group 1, or 31/1,000 catheter
      days; 36 in Group 2, or 36/1,000 catheter-days; P = 0.19). In Group 1, 5
      catheters had 9 recurrent obstructions after successful clearance maneuvers. In
      Group 2, 19 catheters had 40 relapses (P < 0.0001), showing heparin's protective
      role against recurrence of obstruction (Relative Risk = 0.36). However, heparin
      failed to prevent catheter withdrawal due to permanent occlusion (3 catheters in
      Group 1 and 8 in Group 2; P = 0.24). CONCLUSION: Intermittent heparin is not
      effective for preventing the occlusion of peripherally inserted central catheters
      in neonates but reduces relapses when clearance maneuvers were successful.

PMID- 23949407
TI  - Near-infrared spectroscopy for monitoring peripheral tissue perfusion in
      critically ill patients.
AB  - Near infrared spectroscopy (NIRS) is a non-invasive technique that allows
      determination of tissue oxygenation based on spectro-photometric quantitation of
      oxy- and deoxyhemoglobin within a tissue. This technique has gained acceptance as
      a tool to monitor peripheral tissue perfusion in critically ill patient. NIRS
      principle is based on the use of near-infrared electromagnetic waves for
      qualitative and quantitative assessments of molecular factors related to tissue
      oxygenation. Although this technique can be apllied in any tissue, it is
      primarily used for monitoring peripheral oxygenation in the muscle. Parameters
      that are determined using NIRS can be either directly calculated or can be
      derived from physiological interventions, such as arterial and venous occlusions
      methods. Information regarding muscle oxygen saturation, muscle oxygen
      consumption and regional blood flow can therefore be obtained. Clinical
      applications of NIRS include peripheral oxygenation monitoring during
      resuscitation of trauma and septic shock as well as the assessment of regional
      microcirculatory disorders. This review provides a brief discussion of NIRS basic
      principles and main clinical uses of this technique, with a specific focus on
      studies that assess the usefulness of NIRS in intensive care and emergency
      patients. 

PMID- 23949408
TI  - Microcirculatory assessment: a new weapon in the treatment of sepsis?
AB  - The progression into multi-organ failure continues to be a common feature of
      sepsis and is directly related to microcirculatory dysfunction. Based on a PubMed
      database search using the key words microcirculation and sepsis, twenty-six
      articles were selected for this review. The relevant references from these
      articles were also selected and included in this analysis. Orthogonal
      polarization spectral imaging allows for the bedside assessment of the
      microcirculation of critically ill patients. Such imaging has established a
      correlation between microvascular dysfunction and patient outcomes, which allows
      practitioners to directly assess the effects of therapeutic interventions.
      However, the causal relationships between microcirculatory dysfunction, adverse
      outcomes, and the effects of therapies aimed at these microcirculatory changes in
      sepsis, are not clear. 

PMID- 23949409
TI  - Severe Plasmodium falciparum malaria.
AB  - Malaria is one of the world's leading parasitic diseases and affects a
      considerably large number of people. Considering the epidemiological reach of
      Plasmodium falciparum, which is almost always responsible for the most severe
      cases of malaria, a discussion of the clinical features and therapeutic
      interventions is important. In the cases of patients with severe malaria,
      admission to an intensive care unit is mandatory to reduce complications. To have
      an impact on survival rates, treatment with antimalarial drugs and supportive
      measures should be initiated as quickly as possible. The aim of this article is
      to discuss the components of severe malaria, with an emphasis on its clinical
      features and treatment. 

PMID- 23949410
TI  - Effects of kangaroo care during painful procedures in preterm infants: a review.
AB  - Although low-birth neonates are acknowledged to experience pain, many routine
      procedures continue to be conducted without proper pharmacological or non
      pharmacological analgesia. Kangaroo care is a low-cost strategy that can be used
      in the preterm newborn. Mothers should be encouraged to use this easy-to-perform
      method, which is feasible both before and during neonatal units' invasive
      procedures, therefore contributing to pain reduction. 

PMID- 23949412
TI  - Influence of peripheral muscle strength on the decannulation success rate.

PMID- 23949411
TI  - Hemodynamic and respiratory support using venoarterial extracorporeal membrane
      oxygenation (ECMO) in a polytrauma patient.
AB  - There are few reports in the literature regarding the use of venoarterial
      extracorporeal membrane oxygenation (ECMO) for double-dysfunction from both heart
      and lung contusions in polytrauma patients. This article reports a 48-year-old
      patient admitted after a traffic accident. He rapidly progressed to shock with
      low cardiac output due to myocardial contusion and refractory hypoxemia due to
      pulmonary contusion, an unstable chest wall and bilateral pneumothorax. ECMO was
      an effective rescue procedure in this dramatic situation and was successfully
      discontinued on the fourth day after the trauma. The patient also developed an
      extensive brain infarction and eventually died on the seventh day after
      admission. 

PMID- 23949413
TI  - Influence of peripheral muscle strength on the decannulation success rate.

PMID- 23949414
TI  - The stoichiometry and energetics of oxygenic phototrophic growth.
AB  - The values of gross metabolic flows in cells are essentially interconnected due
      to conservation laws of chemical elements and interrelations of biochemical
      coupling. Therefore, the overall stoichiometry of cellular metabolism, such as
      the biomass quantum yield, the ratio between linear and circular flows via the
      electron transport chain, etc., can be calculated using balances of metabolic
      flows in the network branching points and coupling ratios related to ATP
      formation and expenditures. This work has studied the energetic stoichiometry of
      photosynthetic cells by considering the transfer of reductivity in the course of
      biochemical reactions. This approach yielded rigorous mathematical expressions
      for biomass quantum yield and other integral bioenergetic indices of cellular
      growth as functions of ATP balance parameters. The effect of cellular substance
      turnover has been taken into account. The obtained theoretical estimation of
      biomass quantum yield is rather close to experimental data which confirms the
      predictive capacity of this approach. 

PMID- 23949415
TI  - Two new high-resolution crystal structures of carboxysome pentamer proteins
      reveal high structural conservation of CcmL orthologs among distantly related
      cyanobacterial species.
AB  - Cyanobacteria have evolved a unique carbon fixation organelle known as the
      carboxysome that compartmentalizes the enzymes RuBisCO and carbonic anhydrase.
      This effectively increases the local CO2 concentration at the active site of
      RuBisCO and decreases its relatively unproductive side reaction with oxygen.
      Carboxysomes consist of a protein shell composed of hexameric and pentameric
      proteins arranged in icosahedral symmetry. Facets composed of hexameric proteins
      are connected at the vertices by pentameric proteins. Structurally homologous
      pentamers and hexamers are also found in heterotrophic bacteria where they form
      architecturally related microcompartments such as the Eut and Pdu organelles for
      the metabolism of ethanolamine and propanediol, respectively. Here we describe
      two new high-resolution structures of the pentameric shell protein CcmL from the
      cyanobacteria Thermosynechococcus elongatus and Gloeobacter violaceus and provide
      detailed analysis of their characteristics and comparison with related shell
      proteins. 

PMID- 23949416
TI  - Densely arranged two-dimensional silver nanoparticle assemblies with optical
      uniformity over vast areas as excellent surface-enhanced Raman scattering
      substrates.
AB  - Dense two-dimensional assemblies of silver nanoparticles were fabricated over
      vast areas (~19 cm(2)) by utilizing a simple liquid-liquid interface assembly
      technique. The Raman signal for p-aminothiophenol immobilized on the assemblies
      was drastically enhanced by plasmon coupling-induced hot spots, and the enhanced
      signal showed high spatial reproducibility.

PMID- 23949417
TI  - Increased echocardiographic epicardial fat thickness and high-sensitivity CRP
      level indicate diastolic dysfunction in patients with newly diagnosed essential
      hypertension.
AB  - BACKGROUND: Hypertension (HT) is one of the main conditions associated with left
      ventricular (LV) diastolic dysfunction. Epicardial fat tissue (EFT) serves as a
      source of a plenty of proinflammatory cytokines and is associated with increased
      cardiovascular events. The aim of the current study was to evaluate the relation
      among echocardiographically measured EFT thickness, systemic inflammation, and LV
      diastolic dysfunction in patients with essential HT. PATIENTS AND METHODS: The
      study included 135 newly diagnosed and untreated hypertensive outpatients. On the
      basis of conventional Doppler and tissue Doppler imaging-derived parameters,
      patients were divided into two groups: 60 patients with normal diastolic function
      and 75 patients with LV diastolic dysfunction. EFT thickness was measured from
      the parasternal long-axis view at end-systole and high-sensitivity C-reactive
      protein (hs-CRP) was assessed using the latex-enhanced immunoturbidimetric
      method. RESULTS: In patients with LV diastolic dysfunction, EFT thickness was
      significantly increased compared with the normal diastolic function group (7.9 +/
      1.7 vs. 6.3 +/- 1.5 mm; P < 0.001, respectively). Serum hs-CRP level was also
      significantly higher in the LV diastolic dysfunction group (P < 0.001) and was
      correlated with EFT thickness (r = 0.442, P < 0.001). In stepwise multivariate
      logistic regression analysis, EFT thickness (odds ratio 1.27, 95% confidence
      interval 1.12-1.43; P = 0.006) and hs-CRP level (odds ratio 1.42, 95% confidence
      interval 1.18-1.72; P = 0.003) emerged as independent positive predictors of LV
      diastolic dysfunction. CONCLUSION: In patients with newly diagnosed and untreated
      essential HT, increased EFT thickness and hs-CRP level are significantly related
      to impaired LV diastolic function independent from other factors, including age,
      waist circumference, and 24-h systolic blood pressure.

PMID- 23949418
TI  - Competition between hydrogen bonds and halogen bonds in complexes of formamidine
      and hypohalous acids.
AB  - Quantum chemical calculations have been per-formed for the complexes of
      formamidine (FA) and hypohalous acid (HOX, X = F, Cl, Br, I) to study their
      structures, properties, and competition of hydrogen bonds with halogen bonds. Two
      types of complexes are formed mainly through a hydrogen bond and a halogen bond,
      respectively, and the cyclic structure is more stable. For the F, Cl, and Br
      complexes, the hydrogen-bonded one is more stable than the halogen-bonded one,
      while the halogen-bonded structure is favorable for the I complexes. The
      associated H-O and X-O bonds are elongated and exhibit a red shift, whereas the
      distant ones are contracted and display a blue shift. The strength of hydrogen
      and halogen bonds is affected by F and Li substitutents and it was found that the
      latter tends to smooth differences in the strength of both types of interactions.
      The structures, properties, and interaction nature in these complexes have been
      understood with natural bond orbital (NBO) and atoms in molecules (AIM) theories.

PMID- 23949419
TI  - A new reaction mode of germanium-silicon bond formation: insertion reactions of
      H2GeLiF with SiH3X (X = F, Cl, Br).
AB  - A combined density functional and ab initio quantum chemical study of the
      insertion reactions of the germylenoid H2GeLiF with SiH3X (X = F, Cl, Br) was
      carried out. The geometries of all the stationary points of the reactions were
      optimized using the DFT B3LYP method and then the QCISD method was used to
      calculate the single-point energies. The theoretical calculations indicated that
      along the potential energy surface, there were one precursor complex (Q), one
      transition state (TS), and one intermediate (IM) which connected the reactants
      and the products. The calculated barrier heights relative to the respective
      precursors are 102.26 (X = F), 95.28 (X = Cl), and 84.42 (X = Br) kJ mol(-1) for
      the three different insertion reactions, respectively, indicating the insertion
      reactions should occur easily according to the following order: SiH3-Br > SiH3-Cl
      > SiH3-F under the same situation. The solvent effects on the insertion reactions
      were also calculated and it was found that the larger the dielectric constant,
      the easier the insertion reactions. The elucidations of the mechanism of these
      insertion reactions provided a new reaction model of germanium-silicon bond
      formation.

PMID- 23949420
TI  - Reply to: doi:10.1007/s00464-012-2780-8: Re: Robotic single-site hysterectomy:
      feasibility, learning curve and surgical outcome (Surg Endosc 2013;27:2638-2643).
      Vaginal cuff closure: new technologies, old problems.

PMID- 23949421
TI  - Do quantitative birefringence characteristics of meiotic spindle and zona
      pellucida have an impact on implantation in single embryo transfer cycles?
AB  - OBJECTIVE: The aim of this study was to determine whether quantitative PolScope
      characteristics of meiotic spindle and zona pellucida could be used as a non
      invasive marker to predict implantation success in elective single embryo
      transfer cycles. METHODS: Quantitative birefringence parameters; including mean
      retardance, area, length and polar body deviation angle of meiotic spindle and
      mean retardance and width of inner zona pellucida belonging to 53 transfer
      oocytes from elective single embryo transfer cycles were retrospectively
      analyzed. The relevant PolScope features were compared between 20 conception and
      33 non-conception cycles. RESULTS: Meiotic spindle mean retardance, area, length
      and inner zona pellucida mean retardance and width did not reveal a statistically
      significant difference between transfer oocytes from conception and non
      conception cycles. Deviation angle of the polar bodies was also comparable
      between the groups. Spindle and inner zona PolScope characteristics of transfer
      oocytes were not correlated with the maternal age. CONCLUSION: Quantitative
      PolScope features of meiotic spindle and inner zona pellucida can not be used as
      a non-invasive marker to predict assisted reproductive technology success in
      elective single embryo transfer cycles.

PMID- 23949422
TI  - Female patients with pseudomyxoma peritonei: a single-institution
      clinicopathologic study of 35 cases.
AB  - PURPOSE: To explore clinicopathologic/prognostic aspects of pseudomyxoma
      peritonei (PMP). METHODS: We reviewed records of 35 female patients with PMP
      treated at a single institution. RESULTS: Patients' median age was 57.0 years
      (range 35.0-71.0 years). Their median pre-surgery level of carbohydrate antigen
      19-9 (CA-199) was 80.95 U/ml (range 0.00-1,562.10 U/ml); of carbohydrate antigen
      12-5 (CA-125), 44.00 U/ml (range 0.90-231.20 U/ml); and of carcinoembryonic
      antigen (CEA), 17.20 ng/ml (range 2.04-211.60 ng/ml). Of the 35 patients, 23
      (65.7 %) underwent cytoreductive surgery (CRS) by gynecological oncologists and
      12 (34.3 %) underwent non-CRS surgeries by general gynecologists or surgeons,
      including one patient who refused surgical treatment beyond a diagnostic
      laparoscopy. After surgery, 18 patients (51.4 %) had residual lesions, 11 (31.4
      %) had complete lesion removal and 6 (17.1 %)had insufficient information on
      residual lesion; 21 (60.0 %) had appendiceal-based tumors and 12 (34.3 %) had
      ovarian-based tumors. Median follow-up time was 37 months (range 1-148 months),
      during which 28 patients (80.0 %) had relapsed. By the end of the study, 12
      patients (34.3 %) died of PMP, 16 (45.7 %) survived with disease, and 7 (20 %)
      survived without disease. Median progress-free survival (PFS) was 12 months
      (range 0.5-114.0 months). Median overall survival time was 42 months (range 5-150
      months). Ovarian tumor origin, post-surgery residual lesions, preoperative CA199
      > 258.9 U/ml and CA125 > 70.6 U/ml were independent predictors of PFS.
      CONCLUSIONS: PMP is rare in women, and has a poor long-term survival rate. Multi
      center cooperation to gather more cases is needed to explore its behavior and
      proper treatment.

PMID- 23949423
TI  - Hydatid disease of the spleen: single-center experience and a brief literature
      review.
AB  - BACKGROUND: The aim of this study was to discuss the management of patients with
      splenic hydatid cyst (SHC) and to provide a review of the literature in this
      field. METHODS: The outcomes of patients surgically treated for SHC at the
      Diyarbakir Education and Research Hospital (DERH) between January 2006 and May
      2013 were assessed by retrospectively reviewing demographic, radiological, and
      clinical data. In addition, the outcome profiles of these patients were compared
      to the overall outcomes of surgically treated SHC cases reported in the
      literature. Relevant case series (>=4 cases) were identified by searching the
      PubMed, Medline, and Google Scholar databases for publications from 1990 to May
      2013 in English or Turkish languages. RESULTS: Nine patients with SHC received
      surgical treatment at DERH (age range, 18-53 years old; mean, 36.9 +/- 11.8;
      female/male, 7/2), including five (55.6%) primary SHC and four (44.4%) secondary
      (100% liver) SHC cases. Two patients had previous SHC surgery. Seven patients
      received albendazole therapy, both preoperative (10-21 days) and postoperative
      (10-42 days) periods. All patients received vaccination, either preoperative (n =
      4) or postoperative (n = 5). Six patients underwent splenectomy and three
      underwent splenectomy with partial cystectomy and omentopexy, and no patient
      experienced SHC recurrence during follow-up (1-60 months). The literature review
      identified 27 full-text articles representing 333 surgically treated SHC cases,
      among which 60.5% had primary SHC and 39.5% had secondary SHC. Two hundred thirty
      of 333 patients underwent splenectomy, 81 underwent spleen-sparing surgery, and
      17 underwent puncture, aspiration, injection, and reaspiration. The remaining
      five patients were not operated for various reasons. CONCLUSION: We found no
      significant difference in recurrence rates between splenectomy and spleen-sparing
      surgery, either in our patient cohort or among cases reported in the literature.
      Nevertheless, we cannot make any solid recommendations for either procedure based
      on these results, as the studies were largely retrospective.

PMID- 23949424
TI  - Management of electrothermal injury of common bile duct with a degradable biliary
      stent: an experimental study in a porcine model.
AB  - BACKGROUND: Electrothermal injury of common bile duct is a frequent type of
      biliary injury. A long-term postoperative course and biliary leakage after
      removing T-tube are associated with external drainage. A method was developed to
      repair the injury with a degradable biliary stent instead of T-tube insertion.
      METHODS: Pigs were divided into a stent repair (SR) group (n = 18), a T-tube
      repair (TR) group (n = 4), and a suturing repair (SUR) group (n = 4). An
      electrothermal injury model was made by electric coagulation. Pigs in the SR
      group were further divided into five subgroups according to the observation time
      (2 weeks and 1, 3, 6, and 18 months). Pigs in the TR group and SUR group were
      observed for 6 months. Cholangiography was repeated and bilirubin level was
      monitored. Pigs were reoperated for further evaluation at the end of observation.
      RESULTS: No biliary stricture, bile leakage, or bile duct necrosis occurred in
      the SR group. The stent could be detected in the first 2 months. No stent
      migration or stent-related obstruction was observed. Three pigs in the SUR group
      had biliary stricture with elevated bilirubin levels. CONCLUSIONS: These results
      suggested that the developed method for repairing electrothermal injury of common
      bile duct is feasible and safe.

PMID- 23949425
TI  - Risk of neoplastic change in ileal pouches in familial adenomatous polyposis.
AB  - INTRODUCTION: Neoplastic change in ileal reservoirs after proctocolectomy has
      been reported in patients with familial adenomatous polyposis. We aim to
      determine the incidence and progression of neoplastic change in the ileal pouch
      of familial adenomatous polyposis patients at our institution. METHODS: A
      retrospective review of all patients who underwent proctocolectomy for familial
      adenomatous polyposis with construction of an ileal pouch from 1972 to 2007 was
      performed. Data and status at follow-up were retrieved from the Mayo Clinic
      Colorectal Surgery Pouch database. RESULTS: One hundred seventeen patients were
      identified with a median age of 26, 52 were male. Ileal reservoirs included J
      pouch (a = 104), Kock pouch (n = 9), S-pouch (n = 3), and W-pouch (n = 1). Median
      follow-up was 125 months. Polyps were biopsied in 33 patients: non-dysplastic
      polyps (n = 2), low-grade dysplasia (n = 30), and adenocarcinoma (n = 1). No
      patients had high-grade dysplasia. Median time to development of dysplasia was
      149 months. Adenocarcinoma developed in one patient after 284 months. Risk of
      dysplasia at 10, 20, and 25 years was 17, 45, and 69%, respectively. CONCLUSION:
      Though there is a high incidence of low-grade dysplasia in the ileal reservoir in
      familial adenomatous polyposis patients, high-grade dysplasia and cancer occur
      rarely. Patients with low-grade dysplasia may still necessitate regular follow
      up.

PMID- 23949426
TI  - Targeting the ERBB family in cancer: couples therapy.
AB  - The ERBB family of receptor tyrosine kinases has a central role in the
      tumorigenesis of many types of solid tumour. Various therapeutics targeting these
      receptors have been approved for the treatment of several cancers. Considerable
      preclinical data have shown that the administration of two inhibitors against an
      individual ERBB family member--particularly epidermal growth factor receptor
      (EGFR) or ERBB2--leads to markedly higher antitumour activity than the
      administration of single agents. This Opinion article describes the preclinical
      and clinical performance of these dual-targeting approaches, discusses the key
      mechanisms that mediate their increased efficacy and highlights areas for ongoing
      investigation.

PMID- 23949428
TI  - Presenting neuropsychological testing profile of autopsy-confirmed frontotemporal
      lobar degeneration.
AB  - AIMS: We aimed to investigate how neuropsychological test measures at
      presentation might differentiate frontotemporal lobar degeneration (FTLD) from
      Alzheimer's disease (AD). METHODS: We compared autopsy-confirmed FTLD and
      definite AD with Clinical Dementia Rating <=1. Factor scores and t values of each
      neuropsychological test measure were compared between FTLD and AD patients.
      Logistic regression analyses were applied to identify independent predictors
      within test measures for the differentiation of FTLD from AD. RESULTS: Factor
      analyses showed that the memory domain was more severely impaired in AD than in
      FTLD, whereas the language and attention domains were more severely impaired in
      FTLD than in AD. Multiple logistic regression analysis showed that Letter
      Fluency, Boston Naming Test and delayed memory recall remained independent
      predictors of FTLD compared to AD. However, test measures did not discriminate
      between FTLD-tau and FTLD-ubiquitin. CONCLUSION: We confirm that memory and
      language function tests discriminate between FTLD and AD.

PMID- 23949429
TI  - DNA methylation analysis of murine hematopoietic side population cells during
      aging.
AB  - Stem cells have been found in most tissues/organs. These somatic stem cells
      produce replacements for lost and damaged cells, and it is not completely
      understood how this regenerative capacity becomes diminished during aging. To
      study the possible involvement of epigenetic changes in somatic stem cell aging,
      we used murine hematopoiesis as a model system. Hematopoietic stem cells (HSCs)
      were enriched for via Hoechst exclusion activity (SP-HSC) from young, medium-aged
      and old mice and subjected to comprehensive, global methylome (MeDIP-seq)
      analysis. With age, we observed a global loss of DNA methylation of approximately
      5%, but an increase in methylation at some CpG islands. Just over 100 significant
      (FDR<0.2) aging-specific differentially methylated regions (aDMRs) were
      identified, which are surprisingly few considering the profound age-based changes
      that occur in HSC biology. Interestingly, the polycomb repressive complex -2
      (PCRC2) target genes Kiss1r, Nav2 and Hsf4 were hypermethylated with age. The
      promoter for the Sdpr gene was determined to be progressively hypomethylated with
      age. This occurred concurrently with an increase in gene expression with age. To
      explore this relationship further, we cultured isolated SP-HSC in the presence of
      5-aza-deoxycytdine and demonstrated a negative correlation between Sdpr promoter
      methylation and gene expression. We report that DNA methylation patterns are well
      preserved during hematopoietic stem cell aging, confirm that PCRC2 targets are
      increasingly methylated with age, and suggest that SDPR expression changes with
      age in HSCs may be regulated via age-based alterations in DNA methylation. 

PMID- 23949430
TI  - Clinical and laboratory studies of the novel cyclin-dependent kinase inhibitor
      dinaciclib (SCH 727965) in acute leukemias.
AB  - PURPOSE: Dinaciclib inhibits cyclin-dependent kinases 1, 2, 5, and 9 with a
      better therapeutic index than flavopiridol in preclinical studies. This study
      assessed the activity of dinaciclib in acute leukemia both in the clinic and in
      vitro. METHODS: Adults with relapsed/refractory acute myeloid leukemia (n = 14)
      and acute lymphoid leukemia (n = 6) were treated with dinaciclib 50 mg/m(2) given
      as a 2-h infusion every 21 days. RESULTS: Most patients had dramatic but
      transient reduction in circulating blasts; however, no remissions were achieved
      on this schedule. The most common toxicities were gastrointestinal, fatigue,
      transaminitis, and clinical and laboratory manifestations of tumor lysis
      syndrome, including one patient who died of acute renal failure. Dinaciclib
      pharmacokinetics showed rapid (2 h) achievement of maximum concentration and a
      short elimination/distribution phase. Pharmacodynamic studies demonstrated in
      vivo inhibition of Mcl-1 expression and induction of PARP cleavage in patients'
      peripheral blood mononuclear cells 4 h after dinaciclib infusion, but the effects
      were lost by 24 h and did not correlate with clinical outcome. Correlative in
      vitro studies showed that prolonged exposures to dinaciclib, at clinically
      attainable concentrations, result in improved leukemia cell kill. CONCLUSIONS:
      While dinaciclib given as a 2-h bolus did not exhibit durable clinical activity,
      pharmacokinetic and pharmacodynamic data support the exploration of prolonged
      infusion schedules in future trials in patients with acute leukemias.

PMID- 23949431
TI  - Cytochrome P450 oxidoreductase genetic polymorphisms A503V and rs2868177 do not
      significantly affect warfarin stable dosage in Han-Chinese patients with
      mechanical heart valve replacement.
AB  - PURPOSE: To investigate the influence of cytochrome P450 oxidoreductase (POR)
      polymorphisms (A503V and rs2868177) on warfarin stable dosage (WSD) in Han
      Chinese patients with mechanical heart valve replacement (MHVR). METHODS: Three
      hundred and seventeen Han-Chinese MHVR patients on stable maintenance dose of
      warfarin were enrolled. Blood samples were collected for genotyping analyses of
      VKORC1 -1639G>A, CYP2C9 *3, CYP4F2 rs2108622 and POR (A503V and rs2868177).
      Average WSD of carriers with variant POR genotypes or haplotypes were compared.
      Association analyses were performed by single and multiple linear regression
      analysis. RESULTS: The variant allele frequencies of POR polymorphisms (A503V and
      rs2868177) were 38.8 % and 44.8 %, respectively. D' between POR A503V and
      rs2868177 was 0.855, r(2) was 0.375, and the frequencies of the four POR
      haplotypes were 42.3 % for CG, 36.3 % for TA, 18.9 % for CA, and 2.5 % for TG,
      respectively. There were no significant differences in average WSD among carriers
      with three variant POR A503V genotypes or among carriers with three variant POR
      rs2868177 genotypes (both P > 0.05). Similarly, there were no significant
      differences in average WSD among carriers with variant POR haplotypes (all P >
      0.05). Neither single nor multiple linear regression analyses showed significant
      effects of POR A503V or POR rs2868177 polymorphisms on WSD. CONCLUSION: POR
      polymorphisms (A503V and rs2868177) do not appear to significantly influence WSD
      in Han-Chinese patients with MHVR.

PMID- 23949433
TI  - [Importance of multiparametric MRI with respect to seminal vesicle infiltration
      in prostate cancer].

PMID- 23949432
TI  - Recent advances: osteoporosis in the "oldest old".
AB  - Osteoporosis and related fractures disproportionately impact patients with
      advanced age, those with the frailty phenotype, and those with multiple
      comorbidities. Recent studies report a changing incidence in fracture type among
      the oldest old throughout the world, a finding not satisfactorily explained by
      advances in treatment of lifestyle factors. A growing recognition of the
      importance of muscle and bone interaction is leading to improved understanding of
      the underlying biochemical pathways linking them and new therapeutic targets. New
      models of care for frail older populations, particularly after hip fracture, are
      being developed but have been challenged to identify appropriate outcomes to
      target. An appreciation for the relationship between age-related comorbidities,
      fracture risk, and competing mortality risk is essential for practitioners caring
      for the oldest-old population. 

PMID- 23949434
TI  - [PET-MR - a solution looking for a problem?].

PMID- 23949435
TI  - [Multiparametric imaging with simultaneous MR/PET. Methodological aspects and
      possible clinical applications].
AB  - Combined magnetic resonance imaging-positron emission tomography (MR/PET) enables
      acquisition of a variety of imaging parameters during a single examination
      including anatomical as well as functional information, such as perfusion,
      diffusion and metabolism. Numerous studies have shown that the combination of
      these parameters can improve the diagnostic accuracy for many applications
      especially in oncological imaging. Due to the amount and the complexity of the
      acquired multiparametric data there is a need for advanced analytical tools, such
      as methods of parameter selection and data classification. The present article
      summarizes these methods and their applications in multiparametric imaging via
      MR/PET. 

PMID- 23949436
TI  - [Potential of PET/MRI for diagnosis of prostate cancer].
AB  - CLINICAL/METHODICAL ISSUE: A present goal is to improve detection and staging of
      prostate cancer using innovative imaging technology such as PET/MRI. STANDARD
      RADIOLOGICAL METHODS: The modality of choice for detection of prostate cancer is
      multiparametric MRI. Furthermore, PET/CT is used, in particular, for the
      detection and staging of distant metastases and recurrent disease. For assessment
      of bone metastases, the method most commonly used is bone scintigraphy.
      METHODICAL INNOVATIONS: The development of a simultaneous hybrid PET/MRI system
      is the last great "fusion" of the known cross-sectional image modalities. In
      addition, synthesis of new, innovative tracers such as (18)F-FACBC or (68)Ga-PSMA
      allows more specific detection of prostate cancer. PERFORMANCE: Hybrid PET/MRI
      imaging has the potential to replace conventional imaging techniques in the
      future. ACHIEVEMENTS: The method is just starting the broad application. Clinical
      studies must be expanded in order to substantiate the additional value of the
      method. PRACTICAL RECOMMENDATIONS: Currently, there is still a low distribution
      situation, since it is a new and cost-intensive method. At the same time, there
      is still no consistent solution for reimbursement. The importance in practice
      first rises by clarifying the payment situation and further demonstration of the
      method's benefit by larger studies.

PMID- 23949437
TI  - [PET-MR in patients with glioblastoma multiforme].
AB  - Glioblastoma multiforme (GBM) is the most common and most aggressive primary
      tumor of the brain. In recent years newer therapeutic approaches have been
      developed. To allow for an optimized treatment planning it is important to
      precisely delineate necrotic tissue, edema and vital tumor tissue and to identify
      the most aggressive parts of the GBM. The magnetic resonance (MR) portion of an
      MR-positron emission tomography (PET) examination in patients with GBM should
      consist of both structural and functional sequences including diffusion-weighted
      and perfusion sequences. The use of (18)F-fluorodeoxyglucose ((18)F-FDG) is
      limited in patients with gliomas as glucose metabolism is already physiologically
      high in parts of the brain but (18)F-FDG is nevertheless a commonly used
      radiopharmaceutical for neuro-oncological questions. (18)F-fluorothymidine
      reflects the cellular activity of thymidine kinase 1 and correlates with the
      expression of KI-67 as an index of mitotic activity. The nitroimidazole
      derivatives (18)F-fluoromisonidazole and (18)F-fluoroazomycin arabinoside ((18)F
      FAZA) allow the detection of hypoxic areas within the tumor. In recent years
      amino acid tracers, such as (18)F-fluoroethyltyrosine are increasingly being used
      in the diagnosis of gliomas. The simultaneous PET-MR image acquisition allows new
      approaches, e.g. motion correction by the simultaneous acquisition of MR data
      with a high temporal resolution and an improved quantification of the PET signal
      by integrating the results of functional MR sequences. Moreover, the simultaneous
      acquisition of these two time-consuming methods leads to reduced imaging times
      for this, often severely ill patient group. 

PMID- 23949438
TI  - [PET/MRI for cardiac imaging. Possibilities and limits].
AB  - CLINICAL/METHODICAL ISSUE: The positron emission tomography/magnetic resonance
      imaging (PET/MRI) technique represents a new hybrid imaging modality in nuclear
      cardiology. STANDARD RADIOLOGICAL METHODS: The standard radiological method in
      this field is PET/computed tomography (CT). METHODICAL INNOVATIONS: For
      morphological correlation MRI is used instead of CT. Furthermore, the creation of
      attenuation maps (MU-maps) has to be accomplished using MRI data. PERFORMANCE:
      For this new hybrid imaging modality only limited data are so far available,
      especially in the field of nuclear cardiology; however, the available data show a
      relatively good agreement between both modalities with the PET/CT as the modality
      of reference. ACHIEVEMENTS: In comparison to PET/CT a major advantage of PET/MRI
      is the lower radiation dose to the patient; however, the more complex workflow
      using this new imaging modality also has to be taken into account. Furthermore,
      some indications are still at an experimental stage using the PET/MRI. PRACTICAL
      RECOMMENDATIONS: In daily practice, PET/MRI should be considered especially in
      younger patients due to the lower exposure to radiation. Furthermore, there are
      some advantages for this modality in the field of nuclear cardiology, such as
      imaging of inflammatory myocardial processes (e.g. cardiac sarcoidosis) or
      myocardial viability imaging.

PMID- 23949439
TI  - [Contrast in static images in clinical magnetic resonance imaging. Part 2:
      Sequences for various contrast weightings and applications].
AB  - The second part of this educational article focuses on sequence techniques in
      magnetic resonance imaging (MRI) and on suitable parameter sets for different
      contrast weightings. The content is based on the recently published part 1 of
      this educational article providing a survey on tissue properties relevant for
      most important contrast mechanisms. Characteristics of contrast weightings are
      presented in exemplary images recorded from healthy volunteers. Typical clinical
      applications of the most commonly used contrast weightings are described and
      discussed. Sequences for the following contrast weightings are included: proton
      density (density of hydrogen in small mobile molecules), relaxation times T1 and
      T2, chemical shift (water and fat), effects of magnetic susceptibility,
      restricted diffusion of water molecules and magnetization transfer between
      macromolecules and water molecules. 

PMID- 23949441
TI  - Frailty and technology: a systematic review of gait analysis in those with
      frailty.
AB  - BACKGROUND: New technologies for gait assessment are emerging and have provided
      new avenues for accurately measuring gait characteristics in home and clinic.
      However, potential meaningful clinical gait parameters beyond speed have received
      little attention in frailty research. OBJECTIVE: To study gait characteristics in
      different frailty status groups for identifying the most useful parameters and
      assessment protocols for frailty diagnosis. METHODS: We searched PubMed, Embase,
      PsycINFO, CINAHL, Web of Science, Cochrane Library, and Age Line. Articles were
      selected according to the following criteria: (1) population: individuals defined
      as frail, prefrail, or transitioning to frail, and (2) outcome measures:
      quantitative gait variables as obtained by biomechanical analysis. Effect sizes
      (d) were calculated for the ability of parameters to discriminate between
      different frailty status groups. RESULTS: Eleven publications met inclusion
      criteria. Frailty definitions, gait protocols and parameters were inconsistent,
      which made comparison of outcomes difficult. Effect sizes were calculated only
      for the three studies which compared at least two different frailty status
      groups. Gait speed shows the highest effect size to discriminate between frailty
      subgroups, in particular during habitual walking (d = 0.76-6.17). Gait
      variability also discriminates between different frailty status groups in
      particular during fast walking. Prominent parameters related to prefrailty are
      reduced cadence (d = 1.43) and increased step width variability (d = 0.64),
      whereas frailty (vs. prefrail status) is characterized by reduced step length
      during habitual walking (d = 1.32) and increased double support during fast
      walking (d = 0.78). Interestingly, one study suggested that dual-task walking
      speed can be used to predict prospective frailty development. CONCLUSION: Gait
      characteristics in people with frailty are insufficiently analyzed in the
      literature and represent a major area for innovation. Despite the paucity of
      work, current results suggest that parameters beyond speed could be helpful in
      identifying different categories of frailty. Increased gait variability might
      reflect a multisystem reduction and may be useful in identifying frailty. In
      addition, a demanding task such as fast walking or adding a cognitive distractor
      might enhance the sensitivity and specificity of frailty risk prediction and
      classification, and is recommended for frailty assessment using gait analysis.

PMID- 23949442
TI  - LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25.
AB  - Leucine-rich repeat kinase 2 (LRRK2) is a gene that, upon mutation, causes
      autosomal-dominant familial Parkinson's disease (PD). Yeast two-hybrid screening
      revealed that Snapin, a SNAP-25 (synaptosomal-associated protein-25) interacting
      protein, interacts with LRRK2. An in vitro kinase assay exhibited that Snapin is
      phosphorylated by LRRK2. A glutathione-S-transferase (GST) pull-down assay showed
      that LRRK2 may interact with Snapin via its Ras-of-complex (ROC) and N-terminal
      domains, with no significant difference on interaction of Snapin with LRRK2 wild
      type (WT) or its pathogenic mutants. Further analysis by mutation study revealed
      that Threonine 117 of Snapin is one of the sites phosphorylated by LRRK2.
      Furthermore, a Snapin T117D phosphomimetic mutant decreased its interaction with
      SNAP-25 in the GST pull-down assay. SNAP-25 is a component of the SNARE (Soluble
      NSF Attachment protein REceptor) complex and is critical for the exocytosis of
      synaptic vesicles. Incubation of rat brain lysate with recombinant Snapin T117D,
      but not WT, protein caused decreased interaction of synaptotagmin with the SNARE
      complex based on a co-immunoprecipitation assay. We further found that LRRK2
      dependent phosphorylation of Snapin in the hippocampal neurons resulted in a
      decrease in the number of readily releasable vesicles and the extent of
      exocytotic release. Combined, these data suggest that LRRK2 may regulate
      neurotransmitter release via control of Snapin function by inhibitory
      phosphorylation. 

PMID- 23949443
TI  - Apolipoprotein CIII hyperactivates beta cell CaV1 channels through SR-BI/beta1
      integrin-dependent coactivation of PKA and Src.
AB  - Apolipoprotein CIII (ApoCIII) not only serves as an inhibitor of triglyceride
      hydrolysis but also participates in diabetes-related pathological events such as
      hyperactivation of voltage-gated Ca(2+) (CaV) channels in the pancreatic beta
      cell. However, nothing is known about the molecular mechanisms whereby ApoCIII
      hyperactivates beta cell CaV channels. We now demonstrate that ApoCIII increased
      CaV1 channel open probability and density. ApoCIII enhanced whole-cell Ca(2+)
      currents and the CaV1 channel blocker nimodipine completely abrogated this
      enhancement. The effect of ApoCIII was not influenced by individual inhibition of
      PKA, PKC, or Src. However, combined inhibition of PKA, PKC, and Src counteracted
      the effect of ApoCIII, similar results obtained by coinhibition of PKA and Src.
      Moreover, knockdown of beta1 integrin or scavenger receptor class B type I (SR
      BI) prevented ApoCIII from hyperactivating beta cell CaV channels. These data
      reveal that ApoCIII hyperactivates beta cell CaV1 channels through SR-BI/beta1
      integrin-dependent coactivation of PKA and Src. 

PMID- 23949445
TI  - High-throughput sequencing of a single chromosome: a moth W chromosome.
AB  - Y and W chromosomes have mostly been excluded from whole genome sequencing
      projects. Due to the high amount of repetitive sequences they are 'difficult' to
      assemble and therefore need special treatment in the form of, e.g. adapted
      assembly programs, a range of different libraries, and accurate maps, if
      possible. A minimum requirement for these approaches is pure template DNA. We
      therefore microdissected the W chromatin of highly polyploid cells from the flour
      moth, Ephestia kuehniella, and used Roche/454 and Sanger sequencing to generate
      72.6 Mbp of DNA sequence. Nominal coverage was 4.3* of the 16.7 Mbp of W
      chromosomal DNA. We used these data to assess the genetic content of the W
      chromosome. This approach allowed us to determine constituent families of
      transposable elements, microsatellites, and recent insertion sites of
      mitochondrial DNA. However, no conventional protein-coding gene has yet been
      found. The sequence collection is a rich source for the definition of W-specific
      PCR markers and the reconstruction of W chromosome loci, as a step towards full
      reconstruction of the chromosome. 

PMID- 23949446
TI  - Light-mediated in cell downregulation of G-quadruplex-containing genes using a
      photo-caged ligand.
AB  - The use of a caged G-quadruplex ligand allows for transcriptional control of
      quadruplex-containing genes using UV light as an external trigger. An important
      oncogene, SRC, involved in the initiation and proliferation of epithelial tumours
      is shown to be significantly downregulated in cells treated by the caged ligand
      in synergy with UV light treatment. 

PMID- 23949447
TI  - A hierarchical three-dimensional NiCo2O4 nanowire array/carbon cloth as an air
      electrode for nonaqueous Li-air batteries.
AB  - A 3D NiCo2O4 nanowire array/carbon cloth (NCONW/CC) was employed as the cathode
      for Li-air batteries with a non-aqueous electrolyte. After its discharge, novel
      porous ball-like Li2O2 was found to be deposited on the tip of NiCo2O4 nanowires.
      The special structure of Li2O2 and active sites of catalysts are also discussed. 

PMID- 23949444
TI  - Fate choice of post-natal mesoderm progenitors: skeletal versus cardiac muscle
      plasticity.
AB  - Regenerative medicine for skeletal and cardiac muscles still constitutes a
      fascinating and ambitious frontier. In this perspective, understanding the
      possibilities of intrinsic cell plasticity, present in post-natal muscles, is
      vital to define and improve novel therapeutic strategies for acute and chronic
      diseases. In addition, many somatic stem cells are now crossing the boundaries of
      basic/translational research to enter the first clinical trials. However, it is
      still an open question whether a lineage switch between skeletal and cardiac
      adult myogenesis is possible. Therefore, this review focuses on resident somatic
      stem cells of post-natal skeletal and cardiac muscles and their plastic potential
      toward the two lineages. Furthermore, examples of myogenic lineage switch in
      adult stem cells are also reported and discussed. 

PMID- 23949448
TI  - Orthodontic treatment of anterior open bite: a review article--is surgery always
      necessary?
AB  - INTRODUCTION: Anterior open bite cases are very difficult to treat satisfactorily
      because of their multifactorial aetiology and their very high relapse rate.
      Dependent on the origin of the anterior open bite malocclusion and the patient's
      age, there are several treatment possibilities ranging from deterrent appliances,
      high-pull headgear, fixed appliances with and without extractions to orthognathic
      surgery, and skeletal anchorage with miniplates or miniscrews. METHODS: The gold
      standard treatment of skeletal anterior open bite cases is the combined approach
      of orthodontic treatment with fixed appliances and orthognathic surgery. In
      recent years, temporary anchorage devices (TAD) have been developed to correct
      anterior open bites orthodontically. With the introduction of TAD as an effective
      treatment modality, orthognathic surgery may be avoidable in selected anterior
      open bite cases. CONCLUSION: This is a relatively new technique and to date there
      remains a lack of evidence of long-term stability of anterior open bite closure
      with TAD.

PMID- 23949450
TI  - Trismus, opisthotonus and risus sardonicus: who remembers this disease?

PMID- 23949449
TI  - Jaspers' critique of essentialist theories of schizophrenia and the
      phenomenological response.
AB  - This contribution reviews the fin de siecle and immediately following efforts
      (Berze, Gross, Jung, Stransky, Weygandt, and others) to find a fundamental
      psychological disturbance (psychologische Grundstorung) underlying the symptoms
      of dementia praecox, later renamed schizophrenia by Bleuler (1908, 1911). In his
      General Psychopathology (1913), Jaspers brings order into the field by bringing
      to psychopathology a scientific basis coupled with phenomenological rigor. He was
      critical of theories that proposed an essence of schizophrenia, which is merely
      asserted verbally. This imperative is reiterated by other members of the
      Heidelberg School (Gruhle, Mayer-Gross, and K. Schneider). Gruhle (1929)
      contended that the primary symptoms of schizophrenia, indicating an underlying
      but still unknown neurobiological disease process, are independent from one
      another. They cannot be brought under a single, current theoretical model. That
      is, schizophrenia cannot be explained in terms of a 'catchword', which is only
      thought but not empirically studied. Sobered but also inspired by Jaspers' rigor,
      phenomenological psychiatrists (Binswanger, Blankenburg, Conrad, Ey, and others)
      proposed more tempered models, which could be studied empirically or tested
      scientifically. This historical progression may be viewed as a dialectical
      process: First, bold, merely verbal assertions without method were made, then
      Jaspers followed with a sobering critique, and finally, the existential
      phenomenological clinicians/researchers responded by producing fine-grained,
      rigorous phenomenological models, tempered by humility and self-critique, which
      led to hypotheses that could be tested in current clinical neuroscience.

PMID- 23949451
TI  - End-of-life care in Brazilian ICUs is not just a legal issue: adequate training
      and knowledge are essential to improve care.

PMID- 23949452
TI  - Adequate nutrition can improve the outcome of premature infants.

PMID- 23949453
TI  - Guidelines for the management of accidental tetanus in adult patients.
AB  - Although tetanus can be prevented by appropriate immunization, accidental tetanus
      continues to occur frequently in underdeveloped and developing countries. Tetanus
      mortality rates remain high in these areas, and studies regarding the best
      therapy for tetanus are scarce. Because of the paucity of data on accidental
      tetanus and the clinical relevance of this condition, the Associacao de Medicina
      Intensiva Brasileira (AMIB) organized a group of experts to develop these
      guidelines, which are based on the best available evidence for the management of
      tetanus in patients requiring admission to the intensive care unit. The
      guidelines discuss the management of tetanus patients in the intensive care unit,
      including the use of immunoglobulin therapy, antibiotic therapy, management of
      analgesics, sedation and neuromuscular blockade, management of dysautonomia and
      specific issues related to mechanical ventilation and physiotherapy in this
      population. 

PMID- 23949454
TI  - Guidelines for potential multiple organ donors (adult). Part III: organ-specific
      recommendations.
AB  - Brain death (BD) alters the pathophysiology of patients and may damage the
      kidneys, the lungs, the heart and the liver. To obtain better quality transplant
      organs, intensive care physicians in charge of the maintenance of deceased donors
      should attentively monitor these organs. Careful hemodynamic, ventilatory and
      bronchial clearance management minimizes the loss of kidneys and lungs. The
      evaluation of cardiac function and morphology supports the transplant viability
      assessment of the heart. The monitoring of liver function, the management of the
      patient's metabolic status and the evaluation of viral serology are fundamental
      for organ selection by the transplant teams and for the care of the transplant
      recipient. 

PMID- 23949455
TI  - Association between organ dysfunction and cytokine concentrations during the
      early phases of septic shock.
AB  - OBJECTIVE: To investigate the correlation of organ dysfunction and its
      progression with inflammatory response during the early phases of septic shock by
      assessing baseline cytokine concentrations. METHODS: This study included patients
      over 18 years old with septic shock within the first 48 hours after the onset of
      organ dysfunction. Interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL
      10) and C-reactive protein levels were assessed at inclusion and after 24 hours,
      and the differences between these values were calculated. The progression of
      organ dysfunction was assessed using the Sequential Organ Failure Assessment
      (SOFA) score upon admission and 24 hours later for a delta-SOFA determination and
      were categorized as either worsened or improved. The results were expressed as
      means + standard deviation or median (25-75% percentiles). Values with
      descriptive p values of 0.05 or less were considered significant. RESULTS:
      Overall, we included 41 patients with median SOFA scores of 8.0 (6.5-10.0) upon
      admission (T0) and 8.0 (6.0-10.0) 24 hours later (T1). Worsened, improved or
      unchanged SOFA scores were observed in 11 (Group 1), 17 (Group 2) and 13 (Group
      3) patients, respectively. For Group 1, the baseline IL-6, IL-8 and IL-10 values
      were higher, and a significant increase of IL-8 levels was found after 24 hours.
      The change in the SOFA score after 24 hours was significantly, although weakly,
      correlated with baseline IL-6 and IL-8 concentrations. CONCLUSIONS: Higher
      baseline IL-6, IL-8 and IL-10 levels are associated with unfavorable organ
      dysfunction outcomes. Increased IL-8 levels within the first 24 hours are
      correlated with a worsening dysfunction.

PMID- 23949456
TI  - Lethality and osteomuscular and cardiovascular complications in tetanus.
AB  - OBJECTIVE: Despite the decline in the incidence of tetanus, this disease is still
      neglected in the developing world and remains a major cause of morbidity and
      mortality. With improvements in intensive care, it is important to better
      understand the complications of this serious condition. We aim to evaluate 1) the
      lethality and osteomuscular and cardiovascular complications of patients with
      tetanus who are admitted to the intensive care unit (ICU) and 2) the risk factors
      associated with a poor prognosis. METHODS: This was a retrospective study that
      analyzed the medical records of all of the patients diagnosed with tetanus who
      were admitted to an infectious diseases ICU between January 2000 and December
      2001. A standardized form that included demographic, clinical and laboratory data
      was completed. The clinical variables that were related to lethality and
      osteomuscular and cardiovascular complications were described. RESULTS: A total
      of 22 tetanus patients were admitted (81.8% male, mean age of 47.8 years).The
      tetanus infection was associated with professional activities in 54.5% of cases.
      The majority of patients (20 patients) presented with the generalized form of
      disease. Eighty-one percent of the patients had never received a tetanus vaccine
      or were unaware of their vaccine status. Following the injury, none had received
      appropriated passive prophylaxis, only two patients had received surgical
      debridement of wound and six patients received antibiotic therapy. Eleven
      patients (52.4%) experienced some cardiovascular complication. A pressure ulcer
      was the most frequent cardiovascular complication (38.1%), followed by
      arrhythmias (28.6%). Two of the patients developed bone fractures secondary to
      tetanus spasms, corresponding to 9.6% of sample. The tetanus lethality rate was
      9.1%. Higher APACHE II severity scores and very severe status based on the
      Veronesi tetanus classification were significantly associated with the risk of
      death (p=0.04 and 0.03, respectively). The Veronesi classification was also
      associated with the risk of cardiovascular complications (p=0.013) and the length
      of the ICU stay (p=0.009). CONCLUSION: The present study demonstrates the failure
      of primary medical care in vaccination and post-traumatic tetanus prophylaxis.
      Despite improvements in intensive care support, cardiovascular complications are
      still frequent in these patients. Individuals exhibiting high APACHE II scores
      and severe clinical forms of tetanus should be monitored closely due to a risk of
      death and cardiovascular complications.

PMID- 23949457
TI  - Clinical-pathological discrepancies in critically ill patients with difficult
      premortem diagnoses.
AB  - INTRODUCTION: The importance of autopsies is a common theme of discussions both
      in Brazil and around the world as it elucidates causes of death and has wide
      ranging social value. However this is a practice that is gradually being
      considered unnecessary and there have been a decline in the number of postmortems
      examinations. OBJECTIVES: To compare clinical and pathological diagnosis in
      critically ill patients with difficult premortem diagnosis. METHODS: All autopsy
      cases (total of 98) from any of the three general medical/surgical intensive care
      units (78 beds in total) affiliated to the medical school from January 2003 to
      December 2006 were analyzed. We analyzed the clinical and pathological diagnosis
      based on the Goldman criteria. RESULTS: In 49 (50%) cases, there were class I and
      II of Goldman. In contrast, only 30 (30.6%) had a complete agreement between
      premortem and postmortem diagnosis and were classified as class V. Infections had
      a significantly greater rate of concordant diagnosis than cardiovascular
      diseases. CONCLUSION: We found significant discrepancies between clinical and
      pathological findings, reinforcing the value of postmortem examination.

PMID- 23949458
TI  - End of life in intensive care: family members' acceptance of orthotanasia.
AB  - OBJECTIVES: This study aimed to assess family member acceptance of orthotanasia
      as related to symptom management, patient preference and the influence of the
      medical team's communication on therapy. METHODS: This was a descriptive one-year
      study conducted at the adult intensive care unit of the Hospital do Servidor
      Publico Estadual. A structured questionnaire based on the Quality of Dying and
      Death (QODD 22) instrument and prior informal interviews were used. RESULTS:
      Sixty family members were assessed; the mean age was 51.7 + 12.1 years, and 81.7%
      were female. The patients were hospitalized for a mean of 31 + 26.9 days, and
      17.0% of these days were spent in the intensive care unit. Most of the patients
      had neurological conditions. Most of the patients (53.3%) had discussed their end
      of-life care wishes with family members; however, 76.7% of them had not discussed
      this issue with their doctors (p < 0.00). The family members reported being
      favorable to orthotanasia in 83.3% of the cases. Most (85.0%) desired the medical
      team to clearly approach the subject, and 65.0% wished to take part in the
      quality of end-of-life decision making process. The family members were generally
      satisfied with information they received from the doctors: 93.3% believed they
      had received appropriately frequent communications about the clinical conditions;
      81.7% were able to clarify their doubts regarding the patient's clinical status;
      the communication was understood by 83.3% of the respondents; and 80.0% believed
      that clear and honest information had been provided. Only 43.3% of the
      respondents wished to be present at the time of their loved ones' deaths. A
      significant association between family member acceptance of orthotanasia and
      participation in end-of-life decisions (p = 0.042) was observed. CONCLUSIONS:
      Most of the respondents were favorable to orthotanasia and wished to participate
      in end-of-life discussions.

PMID- 23949459
TI  - The neuroprotective role of therapeutic hypothermia after cardiac arrest.
AB  - OBJECTIVES: Therapeutic hypothermia following cardiorespiratory arrest has been
      demonstrated to have cardio- and neuroprotective effects, resulting in improved
      survival and better neurological outcomes. The objective of this study was to
      assess the outcomes of patients undergoing therapeutic hypothermia following
      cardiorespiratory arrest. METHODS: A prospective, 10-month observational study of
      patients admitted to an intensive care unit and undergoing therapeutic
      hypothermia after cardiorespiratory arrest was undertaken. Therapeutic
      hypothermia was induced by cold fluid administration and body surface cooling in
      patients admitted no more than 12 hours after resuscitation from
      cardiorespiratory arrest. A target temperature of 33oC was maintained for 24
      hours. RESULTS: Overall, 12 patients were included (median age 64 years, 58%
      male). Half of the cardiorespiratory arrests were in-hospital. The median first
      day Charlson Index, Sequential Organ Failure Assessment (SOFA) and Acute
      Physiology and Chronic Health Evaluation II scores were of 2.9, 11 and 24.5,
      respectively. The intensive care unit mortality rate was 42% (N=5). Five of the 7
      surviving patients recovered their pre-cardiorespiratory arrest neurological
      status. Hypothermia was initiated 120 min (median) after recovery of spontaneous
      circulation. Most patients (75%) required vasopressor support. During the first 3
      days after cardiorespiratory arrest and therapeutic hypothermia, a progressive
      SOFA score decrease (median 11 on day 0, 10 on day 1 and 7 on day 2) was
      observed. DISCUSSION: In this study, therapeutic hypothermia was applied to all
      post-cardiorespiratory arrest patients and demonstrated good neurological outcome
      in surviving patients.

PMID- 23949460
TI  - Professional profile of pediatric intensivists in Rio de Janeiro, southeastern
      Brazil.
AB  - OBJECTIVE: This study described the sociodemographic profile and professional
      qualifications of pediatric intensive care physicians in the State of Rio de
      Janeiro (RJ), southeastern Brazil. METHODS: This investigation was an
      observational, cross-sectional and descriptive study that was conducted in
      neonatal, pediatric and mixed intensive care units in the State of Rio de
      Janeiro. Physicians working in the participating intensive care units voluntarily
      completed a semistructured and anonymous questionnaire. Questionnaires that were
      not returned within 30 days were considered lost, and questionnaires with less
      than 75% questions completed were excluded. The differences in neonatal and
      pediatric intensive care physicians' medical training were compared using the Chi
      squared test with a 5% significance level. RESULTS: A total of 410 physicians
      were included in this study: 84% female, 48% between 30 and 39 years old and 45%
      with monthly incomes between US $1,700 to 2,700. Forty percent of these
      physicians worked exclusively in this specialty, and 72% worked in more than one
      intensive care unit. Only 50% of the participants had received specific training
      (either medical residency or specialization) in neonatology, and only 33% were
      board-certified specialists in this area. Only 27% of the physicians had received
      specific training in pediatric intensive care medicine, and only 17% were board
      certified specialists (p < 0.0005 for both comparisons). Most (87%) physicians
      had participated in scientific events within the past 5 years, and 55% used the
      internet for continued medical education. However, only 25% had participated in
      any research. Most (63%) physicians were dissatisfied with their professional
      activity; 49% were dissatisfied due to working conditions, 23% due to low incomes
      and 18% due to training-related issues. CONCLUSION: These results suggested that
      the medical qualifications of neonatal and pediatric intensive care physicians in
      the State of Rio de Janeiro, Brazil are inadequate, especially in pediatric
      intensive care medicine. A high level of dissatisfaction was reported, which may
      jeopardize the quality of medical assistance that is provided by these
      professionals.

PMID- 23949461
TI  - Evaluation of postoperative pain experience in intensive care unit patients.
AB  - OBJECTIVE: This study assessed the role of the nursing staff in pain management
      and verified the pain experiences of patients undergoing major surgery and
      receiving postoperative care in the intensive care unit. METHOD: This was a
      prospective, observational study of postoperative patients who were admitted to
      the intensive care unit and later discharged to one of the hospital's regular
      wards. Patients with impaired communication were excluded. All patients signed an
      informed consent form. Data were collected using a questionnaire of 13 pain
      related questions. RESULTS: A total of 167 patients were included, and 69.5% were
      male. Patient age ranged from 50-59 years, and the intensive care unit stay was
      one to three days. The majority of the patients (85%) reported no difficulties in
      expressing their painful symptoms, and the nursing approach in 54.5% of patients
      was only to recognize the presence or absence of pain. No pain scale was used.
      The most painful conditions included the surgical wound and bed positioning.
      CONCLUSION: The nursing team was apparently more concerned with the presence of
      pain than with its quality, severity or possible painful stimuli. Pain scales
      were not used, which suggests the need for continued education of the nursing
      professionals on the manner of approaching their patients and assessing their
      patients' pain.

PMID- 23949462
TI  - Adrenal insufficiency in children with sepsis.
AB  - OBJECTIVE: To determine the frequency of adrenal insufficiency in children
      diagnosed with sepsis that were staying in pediatric intensive care units and to
      establish the association between adrenal function and the use of vasoactive
      drugs, mechanical ventilation time and mortality. METHODS: A cohort-designed
      study was conducted to assess the incidence of adrenal insufficiency in children
      aged 29 days to 12 years who were diagnosed with sepsis using the
      adrenocorticotropic hormone (ACTH) stimulation test. RESULTS: Thirty-nine
      children were included in the study. The frequency of adrenal insufficiency was
      30.7% (12 patients). Children with adrenal insufficiency had an increased need
      for vasoactive drugs as well as longer mechanical ventilation times; however, the
      differences were not statistically significant. A Kaplan-Meier curve indicated
      lower survival rates among the adrenal insufficiency children, but the
      differences were not statistically significant (p = 0.1263). No differences were
      identified between the adrenal sufficiency and adrenal insufficiency groups in
      regards to mechanical ventilation time, use of vasoactive drugs, infection type
      and chronic disease. CONCLUSION: This study determined the frequency of adrenal
      insufficiency in children with sepsis and its relationship to increased mortality
      within the first 28 post-admission days. No statistically significant association
      was found between adrenal insufficiency and mechanical ventilation time or the
      use of vasoactive drugs.

PMID- 23949463
TI  - Clostridium tetani infections in newborn infants: a tetanus neonatorum review.
AB  - Although tetanus is a preventable disease by vaccination, it continues to claim
      lives around the world. Whereas cases of accidental origin reflect insufficient
      population immunization, tetanus neonatorum reveals a double-nature fault-poor
      vaccination coverage of adults coupled with difficulties accessing appropriate
      prenatal care; this situation is aggravated by the extreme severity of tetanus in
      this age group in which the mortality rate can reach up to 80%. The early
      detection of tetanus in neonates is essential for immediately initiating the
      proper therapy. Therefore, although reaching an early diagnosis of tetanus is
      important, the most relevant aspect is related to the appropriate management and
      prophylaxis of this disease. Consequently, the aim of this article is to review
      neonatorum tetanus with an emphasis on its therapy and prevention. 

PMID- 23949464
TI  - Nutritional therapy and neonatal sepsis.
AB  - This article reviews the current understanding of enteral and parenteral
      nutrition therapy in preterm infants, with an emphasis on very low birth weight
      babies. The protective effects of nutrition therapy against neonatal sepsis and
      necrotizing enterocolitis are discussed. Different methods of feeding preterm
      infants are evaluated. Special attention is given to the problems of very low
      birth weight babies and the protective effects of nutrition to counteract
      complications, especially infection. The preferential use of breast milk for
      enteral nutrition, the management of protein and energy offers, the use of early
      and minimal enteral nutrition, the early introduction of parenteral nutrition
      (within the first 24 hours of life) and the use of immunonutrients that are
      appropriately supported by a sufficient number of studies can provide good
      adjuvant therapy guidelines to prevent neonatal sepsis and necrotizing
      enterocolitis. However, we conclude that additional multicenter, randomized
      controlled studies are necessary to clarify the protective role of nutrition in
      preterm infants. Appropriate nutrition is not only effective in treating and
      preventing infective complications, but it also promotes neurodevelopment and
      prevents future harmful consequences. 

PMID- 23949465
TI  - Novel biomarkers in severe community-acquired pneumonia.
AB  - Community-acquired pneumonia (CAP) is the most common infectious disease
      requiring admission to intensive care units (ICUs), and achieving an early and
      precise diagnosis of CAP remains a challenge. Biomarkers play an important role
      in improving clinical judgment in the emergency room and are adjuvant in
      evaluating treatment responses. Novel biomarkers, such as cortisol, pro
      adrenomedullin and endothelin-1, have been shown to be associated with disease
      severity and short-term outcomes. This review article focuses on the clinical use
      of novel biomarkers, severity prediction and treatment monitoring as well as
      future directions of the field. 

PMID- 23949466
TI  - Meningitis and infective endocarditis caused by Rhodotorula mucilaginosa in an
      immunocompetent patient.
AB  - The authors report the case of an immunocompetent man who presented with acute
      impairment of the neurological system, hypertensive crisis and renal failure. The
      patient was eventually diagnosed with Rhodotorula mucilaginosa meningitis and
      infective endocarditis. To the best of our knowledge, this is the first
      description of simultaneous infection of the meninges and endothelium caused by
      Rhodotorula in a non-immunocompromised patient. 

PMID- 23949467
TI  - Acute intermittent porphyria, an important and rare differential diagnosis of
      acute abdomen: case report and literature review.
AB  - Porphyrias are metabolic disorders related to heme biosynthesis pathway enzyme
      dysfunctions. The heme pathway is fundamental for the formation of a number of
      molecules, and such defects cause noxious precursors (porphyrins) to build up.
      Porphyrias are heterogeneously manifested by symptoms that can either be
      neurovisceral, cutaneous, or both, usually during outburst episodes called
      porphyric crises. This article presents a literature review and reports on a case
      of porphyric crisis initially diagnosed as acute abdomen and treated with an
      inconclusive exploratory laparotomy During the postoperative period, the patient
      progressed with tetraparesis, tetraplegia and respiratory distress, suggesting
      Guillain-Barre syndrome, which was precluded after cerebrospinal fluid analysis
      revealed no albumin-cytological dissociation. The patient was admitted to the
      intensive care unit due to her neurological disorders, which required ventilation
      support. After admission, she progressed with choluria and seizures. A porphyric
      crisis was suspected and confirmed upon a 24 hour urine porphyrins test.
      Supportive therapy was initiated, but due to unavailability in our hospital, heme
      derivatives were not given. The patient progressed with nosocomial infection,
      organ dysfunctions and eventually died. Porphyria should be considered as a
      differential diagnosis in acute abdomen cases of unknown origin and associated
      with neurological disorders such as paresis, hydroelectrolytic and psychiatric
      disorders, especially in patients with triggering factors, with a history of
      recurring crises and a family history of porphyria. 

PMID- 23949468
TI  - Creating accountability in image quality analysis. Part 4: quality analytics.

PMID- 23949470
TI  - Angiotensin-(1-7) protects from experimental acute lung injury.
AB  - OBJECTIVES: Recently, recombinant angiotensin-converting enzyme 2 was shown to
      protect mice from acute lung injury, an effect attributed to reduced
      bioavailability of angiotensin II. Since angiotensin-converting enzyme 2
      metabolizes angiotensin II to angiotensin-(1-7), we hypothesized that this effect
      is alternatively mediated by angiotensin-(1-7) and activation of its receptor(s).
      DESIGN: To test this hypothesis, we investigated the effects of intravenously
      infused angiotensin-(1-7) in three experimental models of acute lung injury.
      SETTING: Animal research laboratory. SUBJECTS: Male Sprague-Dawley rats, Balb/c
      mice, and C57Bl6/J mice. INTERVENTIONS: Angiotensin-(1-7) was administered with
      ventilator- or acid aspiration-induced lung injury in mice or 30 minutes after
      oleic acid infusion in rats. In vitro, the effect of angiotensin-(1-7) on
      transendothelial electrical resistance of human pulmonary microvascular
      endothelial cells was analyzed. MEASUREMENTS AND MAIN RESULTS: Infusion of
      angiotensin-(1-7) starting 30 minutes after oleic acid administration protected
      rats from acute lung injury as evident by reduced lung edema, myeloperoxidase
      activity, histological lung injury score, and pulmonary vascular resistance while
      systemic arterial pressure was stabilized. Such effects were largely reproduced
      by the nonpeptidic angiotensin-(1-7) analog AVE0991. Infusion of angiotensin-(1
      7) was equally protective in murine models of ventilator- or acid aspiration
      induced lung injury. In the oleic acid model, the two distinct angiotensin-(1-7)
      receptor blockers A779 and D-Pro-angiotensin-(1-7) reversed the normalizing
      effects of angiotensin-(1-7) on systemic and pulmonary hemodynamics, but only D
      Pro-angiotensin-(1-7) blocked the protection from lung edema and protein leak,
      whereas A779 restored the infiltration of neutrophils. Rats were also protected
      from acute lung injury by the AT1 antagonist irbesartan; however, this effect was
      again blocked by A779 and D-Pro-angiotensin-(1-7). In vitro, angiotensin-(1-7)
      protected pulmonary microvascular endothelial cells from thrombin-induced barrier
      failure, yet D-Pro-angiotensin-(1-7) or NO synthase inhibition blocked this
      effect. CONCLUSIONS: Angiotensin-(1-7) or its analogs attenuate the key features
      of acute lung injury and may present a promising therapeutic strategy for the
      treatment of this disease.

PMID- 23949471
TI  - Complement C5A antagonist treatment improves the acute circulatory and
      inflammatory consequences of experimental cardiac tamponade.
AB  - OBJECTIVE: Cardiogenic shock often leads to splanchnic macro- and
      microcirculatory complications, and these events are linked to local and systemic
      inflammatory activation. Our aim was to investigate the consequences of
      complement C5a antagonist treatment on the early circulatory and inflammatory
      changes in a clinically relevant large animal model of cardiac tamponade. DESIGN
      AND SETTING: A randomized, controlled in vivo animal study in a university
      research laboratory. SUBJECTS: Anesthetized, ventilated, and thoracotomized
      Vietnamese mini pigs (24 +/- 3 kg). INTERVENTIONS: Group 1 (n = 6) served as sham
      operated control. In group 2 (n = 7), cardiac tamponade was induced for 60
      minutes by the administration of intrapericardial fluid, while the mean arterial
      pressure was kept in the interval 40 to 45 mm Hg. Group 3 (n = 6) was treated
      with a complement C5a antagonist compound (the peptide acetyl-peptide-A, 4 mg/kg)
      after 45 minutes of tamponade. MEASUREMENTS AND MAIN RESULTS: The
      macrohemodynamics, including the superior mesenteric artery flow, was monitored;
      the average red blood cell velocity in the small intestinal mucosa was determined
      by an intravital orthogonal polarization imaging technique. The whole blood
      superoxide production, the plasma level of high-mobility group box protein-1 and
      big-endothelin and the small intestinal myeloperoxidase activity were measured.
      One hundred eighty minutes after the relief of tamponade, the mean arterial
      pressure was decreased, while the plasma levels of superoxide, high-mobility
      group box protein-1, and big-endothelin, and the intestinal myeloperoxidase
      activity were increased. The administration of acetyl-peptide-A normalized the
      mean arterial pressure and preserved the cardiac output, while the superior
      mesenteric artery flow and mucosal average red blood cell velocity were increased
      significantly, and the plasma superoxide, high-mobility group box protein-1, big
      endothelin, and intestinal myeloperoxidase levels were reduced. CONCLUSIONS:
      These results provide evidence that blockade of the C5a effects significantly
      influences the acute splanchnic macro- and microhemodynamic complications and
      decreases the potentially harmful inflammatory consequences of experimental
      cardiogenic shock.

PMID- 23949472
TI  - Character and temporal evolution of apoptosis in acetaminophen-induced acute
      liver failure*.
AB  - OBJECTIVE: To evaluate the role of hepatocellular and extrahepatic apoptosis
      during the evolution of acetaminophen-induced acute liver failure. DESIGN AND
      SETTING: A prospective observational study in two tertiary liver transplant
      units. PATIENTS: Eighty-eight patients with acetaminophen-induced acute liver
      failure were recruited. Control groups included patients with nonacetaminophen
      induced acute liver failure (n = 13), nonhepatic multiple organ failure (n = 28),
      chronic liver disease (n = 19), and healthy controls (n = 11). MEASUREMENTS:
      Total and caspase-cleaved cytokeratin-18 (M65 and M30) measured at admission and
      sequentially on days 3, 7, and 10 following admission. Levels were also
      determined from hepatic vein, portal vein, and systemic arterial blood in seven
      patients undergoing transplantation. Protein arrays of liver homogenates from
      patients with acetaminophen-induced acute liver failure were assessed for
      apoptosis-associated proteins, and histological assessment of liver tissue was
      performed. MAIN RESULTS: Admission M30 levels were significantly elevated in
      acetaminophen-induced acute liver failure and non-acetaminophen induced acute
      liver failure patients compared with multiple organ failure, chronic liver
      disease, and healthy controls. Admission M30 levels correlated with outcome with
      area under receiver operating characteristic of 0.755 (0.639-0.885, p < 0.001).
      Peak levels in patients with acute liver failure were seen at admission then fell
      significantly but did not normalize over 10 days. A negative gradient of M30 from
      the portal to hepatic vein was demonstrated in patients with acetaminophen
      induced acute liver failure (p = 0.042) at the time of liver transplant. Analysis
      of protein array data demonstrated lower apoptosis-associated protein and higher
      catalase concentrations in acetaminophen-induced acute liver failure compared
      with controls (p < 0.05). Explant histological analysis revealed evidence of
      cellular proliferation with an absence of histological evidence of apoptosis.
      CONCLUSIONS: Hepatocellular apoptosis occurs in the early phases of human
      acetaminophen-induced acute liver failure, peaking on day 1 of hospital
      admission, and correlates strongly with poor outcome. Hepatic regenerative/tissue
      repair responses prevail during the later stages of acute liver failure where
      elevated levels of M30 are likely to reflect epithelial cell death in
      extrahepatic organs.

PMID- 23949473
TI  - Evaluation of a computer-based educational intervention to improve medical
      teamwork and performance during simulated patient resuscitations.
AB  - OBJECTIVES: To determine the impact of a low-resource-demand, easily disseminated
      computer-based teamwork process training intervention on teamwork behaviors and
      patient care performance in code teams. DESIGN: A randomized comparison trial of
      computer-based teamwork training versus placebo training was conducted from
      August 2010 through March 2011. SETTING: This study was conducted at the
      simulation suite within the Kado Family Clinical Skills Center, Wayne State
      University School of Medicine. PARTICIPANTS: Participants (n = 231) were fourth
      year medical students and first-, second-, and third-year emergency medicine
      residents at Wayne State University. Each participant was assigned to a team of
      four to six members (nteams = 45). INTERVENTIONS: Teams were randomly assigned to
      receive either a 25-minute computer-based training module targeting appropriate
      resuscitation teamwork behaviors or a placebo training module. MEASUREMENTS:
      Teamwork behaviors and patient care behaviors were video recorded during high
      fidelity simulated patient resuscitations and coded by trained raters blinded to
      condition assignment and study hypotheses. Teamwork behavior items (e.g., "chest
      radiograph findings communicated to team" and "team member assists with
      intubation preparation") were standardized before combining to create overall
      teamwork scores. Similarly, patient care items ("chest radiograph correctly
      interpreted"; "time to start of compressions") were standardized before combining
      to create overall patient care scores. Subject matter expert reviews and pilot
      testing of scenario content, teamwork items, and patient care items provided
      evidence of content validity. MAIN RESULTS: When controlling for team members'
      medically relevant experience, teams in the training condition demonstrated
      better teamwork (F [1, 42] = 4.81, p < 0.05; etap = 10%) and patient care (F [1,
      42] = 4.66, p < 0.05; etap = 10%) than did teams in the placebo condition.
      CONCLUSIONS: Computer-based team training positively impacts teamwork and patient
      care during simulated patient resuscitations. This low-resource team training
      intervention may help to address the dissemination and sustainability issues
      associated with larger, more costly team training programs.

PMID- 23949474
TI  - An under-recognized benefit of cardiopulmonary resuscitation: organ
      transplantation.
AB  - OBJECTIVE: For many patients who suffer cardiac arrest, cardiopulmonary
      resuscitation does not result in long-term survival. For some of these patients,
      the evolution to donation of organs becomes an option. Organ transplantation
      after cardiopulmonary resuscitation is not reported as an outcome of
      cardiopulmonary resuscitation and is therefore overlooked. We sought to determine
      the number and proportion of organs transplanted from donors who received
      cardiopulmonary resuscitation after a cardiac arrest in the United States and to
      compare survival of organs from donors who had cardiopulmonary resuscitation
      (cardiopulmonary resuscitation organs) versus donors who did not have
      resuscitation (noncardiopulmonary resuscitation organs). DATA SOURCE: We
      retrospectively analyzed a nationwide, population-based database of all organ
      donors and recipients from the United Network for Organ Sharing between July 1999
      and June 2011. STUDY SELECTION: We queried the database for all organs from
      deceased donors between July 1999 and June 2011. Organs from living donors (n =
      76,015), all organs with missing cardiopulmonary resuscitation data (n = 59), and
      organs procured following a circulatory determination of death (n = 12,030) were
      excluded. DATA EXTRACTION: We report donor demographic data and organ survival
      outcomes among organs from donors who received cardiopulmonary resuscitation
      (cardiopulmonary resuscitation organs) and donors who had not received
      cardiopulmonary resuscitation (noncardiopulmonary resuscitation organs). Graft
      survival of cardiopulmonary resuscitation organs versus noncardiopulmonary
      resuscitation organs was compared using Kaplan-Meier estimates and stratified log
      rank test. DATA SYNTHESIS: In the United States, among the 224,076 organs donated
      by donors who were declared dead by neurologic criteria between 1999 and 2011, at
      least 12,351 organs (5.5%) were recovered from donors who received
      cardiopulmonary resuscitation. Graft survival of cardiopulmonary resuscitation
      organs was not significantly different than that of noncardiopulmonary
      resuscitation organs. CONCLUSIONS: At least 1,000 organs transplanted per year in
      the United States (> 5% of all organs transplanted from patients declared dead by
      neurologic criteria) are recovered from patients who received cardiopulmonary
      resuscitation. Organ recovery and successful transplantation is an unreported
      beneficial outcome of cardiopulmonary resuscitation.

PMID- 23949475
TI  - What affects teacher ratings of student behaviors? The potential influence of
      teachers' perceptions of the school environment and experiences.
AB  - Teachers serve as the natural raters of students within the school and classroom
      contexts. Yet teachers' ratings of their students may vary based on these
      contextual factors. The current study explored the extent to which teacher
      perceptions of the school environment predict their longitudinal ratings of
      student behaviors. Data for this study come from 702 teachers in 42 elementary
      schools. Teachers self-reported their perceptions of the school context at a
      single time point, and provided ratings of their students' behavior via the
      Teacher Observation of Classroom Adaption-Checklist (TOCA-C) across three school
      years. Latent profile analysis identified three latent classes of teachers based
      on their ratings of school organizational health, burnout, and efficacy. A
      regression framework demonstrated an association between the baseline profiles in
      relation to TOCA-C ratings of student behavior across 3 years. Teachers with more
      favorable perceptions of the environment had lower initial ratings of
      concentration problems, disruptive behavior, and internalizing symptoms, and
      higher ratings of prosocial behaviors and family involvement. They also showed
      slower growth in their ratings of emotion dysregulation and greater increases of
      their ratings of family involvement over time. This work is particularly
      important for determining the extent to which teacher ratings may be biased by
      teacher and contextual factors, and may have implications for the identification
      of teachers who may rate students poorly over time.

PMID- 23949476
TI  - Robotic colorectal surgery.
AB  - INTRODUCTION: Minimally invasive surgery has many potential benefits, and the
      application of recently developed robotic technology to patients with colorectal
      diseases is rapidly gaining popularity. QUALITY AND OUTCOMES: However, the
      literature evaluating such techniques, including the outcomes, risks, and costs,
      is limited. In this review, we evaluate and summarize the existing information,
      calling attention to areas where future investigation should occur.

PMID- 23949477
TI  - Response of brain oxygen to therapy correlates with long-term outcome after
      subarachnoid hemorrhage.
AB  - BACKGROUND: Brain oxygen (PbtO2) monitoring can help guide care of poor-grade
      aneurysmal subarachnoid hemorrhage (aSAH) patients. The relationship between
      PbtO2-directed therapy and long-term outcome is unclear. We hypothesized that
      responsiveness to PbtO2-directed interventions is associated with outcome.
      METHODS: Seventy-six aSAH patients who underwent PbtO2 monitoring were included.
      Long-term outcome [Glasgow Outcome Score-Extended (GOS-E) and modified Rankin
      Scale (mRS)] was ascertained using the social security death database and
      structured telephone interviews. Univariate and multivariate regression were used
      to identify variables that correlated with outcome. RESULTS: Data from 64
      patients were analyzed (12 were lost to follow-up). There were 530 episodes of
      compromised PbtO2 (<20 mmHg) during a total of 7,174 h of monitor time treated
      with 1,052 interventions. Forty-two patients (66 %) survived to discharge. Median
      follow-up was 8.5 months (range 0.1-87). At most recent follow-up 35 (55 %)
      patients were alive, and 28 (44 %) had a favorable outcome (mRS <=3). In
      multivariate ordinal regression analysis, only age and response to PbtO2-directed
      intervention correlated significantly with outcome. Increased age was associated
      with worse outcome (coeff. 0.8, 95 % CI 0.3-1.3, p = 0.003), and response to
      PbtO2-directed intervention was associated with improved outcome (coeff. -2.12,
      95 % CI -4.0 to -0.26, p = 0.03). Patients with favorable outcomes had a 70 %
      mean rate of response to PbtO2-directed interventions whereas patients with poor
      outcomes had a 45 % response rate (p = 0.005). CONCLUSIONS: Response to PbtO2
      directed intervention is associated with improved long-term functional outcome in
      aSAH patients.

PMID- 23949478
TI  - Urgent laparoscopic repair of acutely symptomatic PEH is safe and effective.
AB  - BACKGROUND: Acute incarceration of paraesophageal hernias (PEHs) requiring urgent
      or emergent surgery is rare. Patients are often elderly with significant
      comorbidities and have historically been treated with open abdominal or thoracic
      incisions. Our study was designed to evaluate the feasibility, safety, and
      efficacy of laparoscopic paraesophageal hernia repair (LPEHR) in patients with
      PEH and acute gastric volvulus. METHODS: We reviewed our prospectively maintained
      database and identified 269 patients who underwent an initial LPEHR between
      January 2003 and January 2012. Patients were divided into group A (acute), group
      B (age- and comorbidity-matched 1:3), and group C (all elective repairs). Group A
      included those admitted with acute symptoms related to PEH and underwent urgent
      repair. Patient age, Charlson score, operative time, length of stay (LOS),
      morbidity, mortality, and recurrence rates were compared. RESULTS: Patients who
      underwent urgent LPEHR had a higher perioperative morbidity rate than the
      elective and matched groups. The overall mortality rate was low and no
      statistical difference was found between groups A, B, and C. LOS in group A was
      longer than groups B and C. The need for ICU admission was also higher in group
      A. There was no statistical difference in recurrence rates. CONCLUSIONS:
      Historically, patients presenting with acute symptoms related to PEH have
      required open repair, which is associated with significant morbidity and
      mortality. The acute group was older and sicker than our elective LPEHR patients
      and had more adverse events resulting in a longer LOS, even when compared with
      comorbidity-matched elective patients. However, the LOS remained shorter than
      that reported for open repair and there was no mortality. The recurrence rates in
      all groups were low and comparable to elective repairs.

PMID- 23949479
TI  - Diaphragmatic relaxing incisions during laparoscopic paraesophageal hernia
      repair.
AB  - BACKGROUND: Laparoscopic paraesophageal hernia (PEH) repair is associated with an
      objective recurrence rate exceeding 50% at 5 years. Minimizing tension is a
      critical factor in preventing hernia recurrence. This study aimed to evaluate the
      outcomes of crural relaxing incisions in patients undergoing PEH repair. METHODS:
      Records were reviewed to identify patients who received a relaxing incision
      during laparoscopic PEH repair. The patients were followed by chest X-ray and
      videoesophagram at 3 months and then annually. RESULTS: From November 2010 to
      March 2013, 58 patients underwent PEH repair, and 15 patients received a relaxing
      incision to accomplish crural closure. The median age of the patients was 72
      years (range 58-84 years). The relaxing incision was right-sided in 13 patients,
      left-sided in one patient, and bilateral in one patient. All the procedures were
      completed laparoscopically and included a fundoplication. Collis gastroplasty for
      a short esophagus was performed for 40% of the patients. No major complications
      occurred. During a median follow-up period of 4 months, one patient had an
      asymptomatic mildly elevated left hemidiaphragm, and one patient had a trivial
      recurrent hernia, as shown on esophagogastroduodenoscopy (EGD). CONCLUSION:
      Crural tension likely contributes to the high recurrence rate noted with
      laparoscopic PEH repair. Relaxing incisions are safe and allow crural
      approximation. Advanced laparoscopic surgeons should be aware of this option when
      faced with a large hiatus in a patient with PEH.

PMID- 23949480
TI  - Laparoendoscopic single-site versus conventional laparoscopic total
      extraperitoneal hernia repair: a prospective randomized clinical trial.
AB  - BACKGROUND: This study aimed to compare laparoendoscopic single-site (LESS) total
      extraperitoneal (TEP) repair with conventional laparoscopic TEP repair for the
      treatment of inguinal hernias. To date, no other studies have compared the LESS
      and conventional laparoscopic TEP approaches for the treatment of inguinal hernia
      in a prospective randomized study setting. METHODS: For this study, 100 patients
      undergoing inguinal hernia repair were prospectively randomized into either the
      LESS TEP group or the conventional laparoscopic TEP group. Pre-, intra-, and
      postoperative factors were recorded. The primary end point was postoperative
      pain. The patients were interviewed at outpatient clinics at 1 week, 3 months,
      and 6 months postoperatively. RESULTS: The demographic data were comparable
      between the two groups. The median operative time was longer in the LESS TEP
      group (63.5 min) than in the conventional TEP group (50.5 min) (p = 0.001). No
      conversion was performed in either group. The mean pain score 2 h postoperatively
      during rest was significantly higher in the conventional TEP group than in the
      LESS TEP group (3.9 vs. 2.6; p = 0.02). The postoperative results were comparable
      between the groups in terms of analgesic requirements, systemic stress responses,
      complications, and postoperative convalescence. CONCLUSIONS: The LESS TEP
      technique is associated with a longer operative time but offers the minor benefit
      of a reduction in immediate postoperative pain.

PMID- 23949481
TI  - Totally laparoscopic anterior resection with transvaginal assistance and
      transvaginal specimen extraction: a technique for natural orifice surgery
      combined with reduced-port surgery.
AB  - BACKGROUND: Natural orifice specimen extraction (NOSE) has been developed as a
      means of decreasing the incidence of surgical wound complications. However, NOSE
      performed using a conventional multiport technique has been reported previously.
      The current authors performed totally laparoscopic anterior resection with
      transvaginal specimen extraction (TVSE) using the reduced-port surgery (RPS)
      technique. The Alexis wound retractor (Applied Medical, Rancho Santa Margarita,
      CA, USA) and Free Access (Top Corporation, Tokyo, Japan) were attached to the
      transvaginal route for transvaginal assistance and smooth specimen extraction.
      The authors documented this simple and safe technique and its short-term results.
      METHODS: Data were prospectively collected for five patients who underwent
      totally laparoscopic anterior resection with TVSE for colorectal cancer between
      June 2012 and December 2012. A multiport access device (GelPOINT advanced-access
      platform; Applied Medical) was inserted into the navel, and a 5-mm port was
      inserted into the right lower quadrant to be used as a drain site. Transverse
      transvaginal posterior colpotomy then was performed. One ring of an Alexis ring
      pair was inserted into the peritoneal cavity through the vagina. The other white
      ring was placed outside of the vagina and then covered with a Free Access to
      maintain the pneumoperitoneum for insertion of a 12-mm port. Lymph node
      dissection and transection of the distal colon were performed with transvaginal
      assistance. The specimen then was extracted transvaginally. After the Alexis had
      been removed, the vaginal incision was closed transvaginally. End-to-end
      colorectal anastomosis was performed using the double-stapling technique.
      RESULTS: Transvaginal extraction was completed in all five cases. The median
      operation time was 235 min. One case was complicated by chyloperitoneum. The
      median hospital stay was 6 days. Only one patient required intravenous analgesics
      once on postoperative day 1. All the patients remained disease free. CONCLUSION:
      Totally laparoscopic anterior resection using TVSE with RPS appears to be
      feasible, safe, and oncologically acceptable for selected cases.

PMID- 23949482
TI  - A call to arms: obese men with more severe comorbid disease and underutilization
      of bariatric operations.
AB  - BACKGROUND: Despite similar rates of obesity among American men and women,
      population-based studies suggest that bariatric surgery patients are
      disproportionately female. We sought to assess this observation quantitatively.
      METHODS: Data were prospectively collected from 1,368 consecutive patients
      evaluated for bariatric surgery over a 4-year period. The prevalence of diabetes
      mellitus (DM), hypertension (HTN), dyslipidemia (DYS), obstructive sleep apnea
      (OSA), gastroesophageal reflux disease, depression, back pain (BKP), and
      musculoskeletal peripheral disease was assessed. A severity score from 1 to 5 had
      been assigned to each comorbidity based on the Assessment of Obesity Related
      Comorbidities Scale (AORC). Metabolic syndrome (MetS) was defined as the
      concurrent presence of DM, HTN, and DYS. RESULTS: The majority of patients were
      female (n = 1,115, 81.5%). Male patients were older (44.5 +/- 9.5 vs. 42.6 +/-
      9.6 years, p = 0.0044) and had higher body mass index (48.7 +/- 7.8 vs. 46.6 +/-
      7.4 kg/m(2), p < 0.0001). On average, men presented with 4.54 serious
      comorbidities and 3.7 complicated comorbidities (AORC score >=3), whereas women
      presented with 4.15 serious comorbidities and 3.08 complicated comorbidities.
      More men presented with DM (36.4 vs. 28.9%, p = 0.0154), HTN (68.8 vs. 55.3%, p =
      0.0001), OSA (71.9 vs. 45.7%, p < 0.0001), and MetS (20.9 vs. 15.2%, p = 0.0301).
      Men also presented with more complicated DM (33.2 vs. 23.9%, p = 0.0031), DYS
      (36.8 vs. 23.5%, p < 0.0001), HTN (58.9 vs. 44.6%, p < 0.0001), BKP (25.3 vs.
      19.3%, p = 0.0378), OSA (56.9 vs. 30.1%, p < 0.0001), and MetS (17.8 vs. 10.0%, p
      = 0.001). CONCLUSIONS: Although men typically comprise less than 20% of bariatric
      surgery patients, they potentially have more to gain from these operations. Men
      present later in life, with more advanced obesity, and with more complicated
      comorbidities. Such findings mandate more research and resources to investigate
      this barrier to treatment and to provide the morbidly obese male with the
      surgical care he clearly needs.

PMID- 23949483
TI  - Pilot study comparing the leak pressure of the sleeved stomach with and without
      reinforcement.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) consists of a longitudinal
      resection of the stomach on the greater curvature, removing 75-80% of the stomach
      approximately and creating a cylindrical "sleeve"-like conduit. However, LSG can
      be associated with significant morbidity, and staple-line failure with dehiscence
      and gastric leak is one of the most severe complications. The aim of this study
      was to compare three different methods of gastric closure in terms of staple-line
      strength and leak pressures of the sleeved stomach. METHODS: After performing
      standard stapled sleeve gastrectomies, the gastric specimens were carefully
      retrieved. Group 1 specimens were left with the staple line intact. In group 2,
      the staple line was reinforced with a 3-0 polypropylene running suture. The
      gastric remnants of group 3 were those in which the LSG was performed using
      Seamguard as the buttressing material. The burst-pressure was assessed using a
      portable gas sensor. The outcome parameters were: age of the patients, body mass
      index, buttress material (suture, Seamguard, etc.), leak pressure, volume
      infused, and leak site, among others. RESULTS: Thirty-six sleeve gastrectomies
      were included in the final analysis. Each group consisted of 12 gastric
      specimens. There were no differences between groups in terms of age, sex, body
      mass index, and patient comorbidities. The leak pressure was significantly higher
      in group 2 (35 +/- 11.7 vs. 102 +/- 21.4 vs. 47 +/- 19.1; p = <0.0005). The
      volume of liquid required to cause the leak was much greater in the group 3 (p =
      <0.001). CONCLUSIONS: Oversewing is the reinforcement method that increases
      better the staple-line strength. It is the least expensive method of
      reinforcement and does not increase operative times significantly.

PMID- 23949484
TI  - Effect of bariatric surgery on oncologic outcomes: a systematic review and meta
      analysis.
AB  - BACKGROUND: Obesity is a major public health issue and is associated with
      increased risk of several cancers, currently a leading cause of mortality. Obese
      patients undergoing bariatric surgery may allow for evaluation of the effect of
      intentional excess weight loss on subsequent risk of cancer. We aimed to evaluate
      cancer risk, incidence, and mortality after bariatric surgery. METHODS: A
      comprehensive literature search was conducted using PubMed/MEDLINE and Embase
      with literature published from the inception of both databases to January 2012.
      Inclusion criteria incorporated all human studies examining oncologic outcomes
      after bariatric surgery. Two authors independently reviewed selected studies and
      relevant articles from their bibliographies for data extraction, quality
      appraisal, and meta-analysis. RESULTS: Six observational studies (n = 51,740)
      comparing relative risk (RR) of cancer in obese patients undergoing bariatric
      surgery versus obese control subjects were analyzed. Overall, the RR of cancer in
      obese patients after undergoing bariatric surgery was 0.55 [95% confidence
      interval (CI) 0.41-0.73, p < 0.0001, I(2) = 83%]. The effect of bariatric surgery
      on cancer risk was modified by gender (p = 0.021). The pooled RR in women was
      0.68 (95% CI 0.60-0.77, p < 0.0001, I(2) < 0.1%) and in men was 0.99 (95% CI 0.74
      1.32, p = 0.937, I(2) < 0.1%). CONCLUSIONS: Bariatric surgery reduces cancer risk
      and mortality in formerly obese patients. When stratifying the meta-analysis by
      gender, the effect of bariatric surgery on oncologic outcomes is protective in
      women but not in men.

PMID- 23949485
TI  - Predictive factors for development of chronic pouchitis after ileal pouch-anal
      anastomosis in ulcerative colitis.
AB  - BACKGROUND: No previous studies have examined predictive factors for chronic
      pouchitis after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC)
      with consideration of changes in pouchitis subtypes during follow-up. This study
      evaluated the independent predictive factors for chronic pouchitis. METHODS: A
      total of 244 consecutive patients who underwent IPAA were enrolled. We assessed
      the possible associations between pouchitis and clinical factors using Cox
      proportional hazard regression. RESULTS: 231 patients met the inclusion criteria.
      66 (28.5%) patients developed pouchitis. In 9 of 44 (20.4%) patients, antibiotic
      responsive pouchitis at the first episode changed into chronic pouchitis after
      the occurrence of a subsequent episode. The median duration from occurrence of
      antibiotic-responsive pouchitis to alteration into chronic pouchitis was 502
      (range 147-1,697) days. Overall pouchitis was finally classified into 35 acute
      pouchitis and 31 chronic pouchitis cases. Multivariate analysis revealed that a
      >= 7.5-g cumulative steroid dose before colectomy and a >= 500-mg monthly steroid
      dose just before colectomy were significant predictive factors for chronic
      pouchitis (p = 0.0001 and 0.0095, respectively). CONCLUSION: Patients with UC and
      a higher cumulative steroid dose before colectomy or higher monthly steroid dose
      just before colectomy may have a predictive factor for developing chronic
      pouchitis.

PMID- 23949488
TI  - 'Spontaneous haemorrhage in an eyelid hidrocystoma in a patient treated with
      clopidogrel' by Tehrani et al.

PMID- 23949487
TI  - Selective fluorescent detection of aspartic acid and glutamic acid employing
      dansyl hydrazine dextran conjugate.
AB  - Highly water soluble polymer (DD) was prepared and evaluated for its fluorescence
      response towards various amino acids. The polymer consists of dansyl hydrazine
      unit conjugated into dextran template. The conjugation enhances higher water
      solubility of dansyl hydrazine moiety. Of screened amino acids, DD exhibited
      selective fluorescence quenching in the presence of aspartic acid (Asp) and
      glutamic acid (Glu). A plot of fluorescence intensity change of DD against the
      concentration of corresponding amino acids gave a good linear relationship in the
      range of 1 * 10(-4) M to 25 * 10(-3) M. This establishes DD as a potential
      polymeric sensor for selective sensing of Asp and Glu.

PMID- 23949486
TI  - The link between suicide and insomnia: theoretical mechanisms.
AB  - Insomnia has been established as a risk factor for depression and mental illness
      for decades, but a growing body of evidence has recently exposed insomnia to be
      an independent risk factor for suicide that encompasses all age ranges. This
      discovery has invigorated investigation to elucidate the relationship between
      insomnia and suicide, and over 20 studies reinforcing this association in adults
      have been published since 2010 alone. This article analyzes relevant research and
      emphasizes studies published within the last three years with the intent of
      proposing theoretical mechanisms explaining the link between suicide and
      insomnia. These mechanisms may then be used as targets for future investigation
      of treatment. 

PMID- 23949490
TI  - Management of macular hole retinal detachment and macular retinoschisis secondary
      to pathological myopia: a national survey of UK practice patterns.

PMID- 23949489
TI  - Bevacizumab as an adjunct to vitreoretinal surgery for diabetic retinopathy in
      East Africa.
AB  - PURPOSE: The purpose of this study is to evaluate the efficacy of preoperative
      intravitreal bevacizumab (IVB) for improving outcomes in vitrectomy for diabetic
      retinopathy-related non-clearing vitreous haemorrhage and/or tractional retinal
      detachment. METHODS: Medical record from patients undergoing vitrectomy for
      proliferative diabetic retinopathy (PDR) were retrospectively analysed (2003
      2011). From 2007, IVB (1.25 mg 2-4 days before operating) was used on all eyes.
      Eyes receiving IVB were compared with those that did not receive IVB.
      Intraoperative complications, reoperation rates, and final visual acuity were the
      core outcome measures. RESULTS: Data were analysed for 88 patients (101 eyes). In
      all, 41 (41%) patients had received IVB, whereas 60 (59%) patients had not.
      Significant intraoperative haemorrhage occurred in six eyes (10%) in the non-IVB
      group and in one (2.4%) IVB eyes (P=0.24). Silicon oil was used in 29 (48%) non
      IVB eyes and in 11 (27%) IVB eyes (P=0.03). The non-IVB eyes underwent
      significantly more vitreoretinal reoperations (P=0.01) and were significantly
      more likely to lose two or more lines of vision at the final follow-up (P=0.03).
      The numbers needed to treat (NNT) blindness (<3/60) was four for non-IVB eyes and
      two for the IVB group. CONCLUSIONS: IVB reduces surgical complications, the use
      of silicon oil, and the need for further retinal surgery. The NNT to restore
      useful vision (>=3/60) to a blind eye were significantly lower in the IVB group.
      Vitreoretinal surgery for the complications of PDR is effective in an East
      African context, and IVB should be considered a valuable adjunct.

PMID- 23949491
TI  - Surgical treatment of 32 cases of long-term atopic keratoconjunctivitis using the
      amniotic membrane.
AB  - PURPOSE: To evaluate the use of surgical treatment with amniotic membrane for
      long-term atopic keratoconjunctivitis. Damaged corneas were repaired with various
      techniques: amniotic membrane transplantations, amniotic membrane coverings,
      amniotic membrane fillings (AMFs), and amniotic membrane inlay fillings, the
      latter of which were combined with glycerol-preserved corneal transplants.
      METHODS: This retrospective study was conducted on 37 eyes belonging to 37
      patients with atopic keratoconjunctivitis. Thirty-two patients were classified
      into four groups according to surgical technique. Five patients undergoing
      medical management served as controls. Surgical outcome was measured by recovery
      time and long-term visual improvement. RESULTS: In all surgical eyes, integrity
      of ocular tissues was effectively restored and symptoms were reduced at 24.4 +/-
      13 days post recovery. Mean best-corrected visual acuity improved from 0.6 +/-
      0.2 to 0.198 +/- 0.16 logarithm of the minimum angle of resolution (P<0.001).
      There were no intraoperative or postoperative complications, with the exception
      of two recurring cases, both controlled by medication. Recovery time of the
      control groups lasted 52 +/- 16 days. In controls, mean best-corrected visual
      acuity improved from 0.74 +/- 0.15 to 0.54 +/- 0.29 logarithm of the minimum
      angle of resolution (P <= 0.05). The vision improvement has significant
      difference for surgical treatment vs medical. (Mann-Whitney U-test, U = 119, P <
      0.05, one tailed).Vision improvements remained stable during a mean follow-up
      period of 21.7 +/- 3.8 months. CONCLUSION: Patients suffering from severe chronic
      atopic keratoconjunctivitis and its complications can benefit from suitable
      surgical treatments: transplants, covers, fillings, or corneal graft surgeries
      supplemented with AMFs.

PMID- 23949492
TI  - Comment on 'Spontaneous haemorrhage in an eyelid hidrocystoma in a patient
      treated with clopidogrel'.

PMID- 23949494
TI  - Phenotype/genotype correlation in a case series of Stargardt's patients
      identifies novel mutations in the ABCA4 gene.
AB  - PURPOSE: To investigate phenotypic variability in terms of best-corrected visual
      acuity (BCVA) in patients with Stargardt disease (STGD) and confirmed ABCA4
      mutations. METHODS: Entire coding region analysis of the ABCA4 gene by direct
      sequencing of seven patients with clinical findings of STGD seen in the Retina
      Clinics of Southampton Eye Unit between 2002 and 2011.Phenotypic variables
      recorded were BCVA, fluorescein angiographic appearance, electrophysiology, and
      visual fields. RESULTS: All patients had heterozygous amino acid-changing
      variants (missense mutations) in the ABCA4 gene. A splice sequence change was
      found in a 30-year-old patient with severly affected vision. Two novel sequence
      changes were identified: a missense mutation in a mildly affected 44-year-old
      patient and a frameshift mutation in a severly affected 34-year-old patient.
      CONCLUSION: The identified ABCA4 mutations were compatible with the resulting
      phenotypes in terms of BCVA. Higher BCVAs were recorded in patients with missense
      mutations. Sequence changes, predicted to have more deleterious effect on protein
      function, resulted in a more severe phenotype. This case series of STGD patients
      demonstrates novel genotype/phenotype correlations, which may be useful to
      counselling of patients. This information may prove useful in selection of
      candidates for clinical trials in ABCA4 disease.

PMID- 23949493
TI  - Vital dyes increase the rigidity of the internal limiting membrane.
AB  - PURPOSE: To assess the stiffness of the natural human internal limiting membrane
      (ILM) and evaluate potential changes of the mechanical properties following
      staining with brilliant blue (BB) and indocyanine green (ICG). METHODS: Unstained
      ILM specimens were obtained during ophthalmic surgical procedures. After removal,
      the specimens were dissected into five parts. Two fragments were stained with BB
      and ICG, respectively, for 1 min, another two specimens were stained similarly
      followed by additional subsequent illumination using a standard light source
      (PENTA LUX x 50, Ophthalmologische Systeme GmbH Fritz Ruck). The fifth part
      served as an untreated control. All specimens were then analyzed using atomic
      force microscopy (AFM) in contact mode with a scan rate of 0.6 Hz. Two scan
      regions of 10 * 10 MUm were chosen and stiffness was determined by using AFM in a
      force spectroscopy mode. The force curves were plotted with a data rate of 5000
      Hz. In all specimens both the retinal side and vitreal side were analyzed.
      RESULTS: Staining resulted in a significant increase in tissue stiffness. An
      increase was seen both for the vitreal (BB: P<0.001; ICG: P<0.01) and retinal
      side (BB: P<0.01; ICG: P<0.01), with the retinal side being significantly stiffer
      in all control and stained samples. Additional illumination after staining did
      further increase tissue rigidity in most samples but not significantly.
      CONCLUSIONS: Staining significantly increases the stiffness of the human ILM.
      This might explain the fact that the stained ILM can be removed more easily and
      in larger fragments during vitreoretinal surgical procedures compared with
      unstained ILM.

PMID- 23949495
TI  - Identifying the time to change BCR-ABL inhibitor therapy in patients with chronic
      myeloid leukemia.
AB  - Many patients newly diagnosed with chronic myeloid leukemia in the chronic phase
      (CML-CP) respond to imatinib. Those experiencing imatinib resistance/intolerance
      require alternative treatments. Delayed responses increase the risk of
      transformation to advanced disease, mutation development and loss of response. In
      retrospective analyses, achieving faster, deeper responses correlated with
      improved long-term response and outcome. Changing therapy to obtain early
      responses may improve the depth and speed of response, ultimately improving the
      outcome. Although trials are ongoing, there are no prospective data indicating
      that changing from imatinib to later-generation inhibitors reverses the inferior
      prognosis and improves the outcome. We describe the rationale behind early
      therapy change in CML-CP. 

PMID- 23949497
TI  - [Primary health care].

PMID- 23949498
TI  - [Primary health care: a pending commitment].

PMID- 23949499
TI  - [Use of health facilities of the Ministry of Health of Peru, 2009-2011].
AB  - OBJECTIVE: To describe the use of health services and associated factors in
      health care centers of the Ministry of Health of Peru (MINSA). MATERIALS AND
      METHODS: An ecological study was conducted with information from outpatients
      placed in all health centers from all Regions at the national level from 2009
      2011. The use of health services was defined by the proportion of outpatient and
      the total population. This variable was compared by gender, age group, geographic
      area, and calendar year. Chi-square test was performed to compare proportions
      between the different layers. In addition, linear regression was performed to
      determine factors associated. RESULTS: In this period of time there was an
      increased number of health care centers and health insurance coverage, but the
      use of health services decreased from 43.3% (2009) to 40.3% (2011). An increased
      use by female residents, age group of 0-29 years old and residents from the
      southern region was found. A multivariate analysis was conducted and factors
      associated with use of health systems were geographic area, and calendar year.
      CONCLUSIONS: Use of health services is not associated to the increased number of
      health centers nor the access to health insurance, but it is associated to
      individual factors or health system-related factors that should be evaluated in
      future studies.

PMID- 23949496
TI  - Functions of the aryl hydrocarbon receptor in the skin.
AB  - Among other functions, the skin serves as the barrier against the environment and
      provides vital protection from physical or chemical harm and from infection. Skin
      cells express the aryl hydrocarbon receptor (AHR), a ligand-activated
      transcription factor and sensor of environmental chemicals; at the same time, AHR
      ligands are abundant in skin from exogenous or endogenous sources. For example,
      solar radiation, in particular ultraviolet (UV) B, generates AHR ligands from
      tryptophan in the skin. Recent evidence has shown that AHR is involved in the
      (patho)physiology of skin including the regulation of skin pigmentation,
      photocarcinogenesis, and skin inflammation. We here provide a state-of-the-art
      summary of work which relates to the role of the AHR in (1) adaptive responses
      against environmental challenges such as UVB or topical chemicals and (2)
      intrinsic developmental roles for homeostasis of skin cells and (3) skin
      immunity. We also discuss the existing evidence that AHR antagonists or AHR
      ligands may be used for the prevention and/or treatment of skin disease. 

PMID- 23949500
TI  - [Preferences of antibiotic use in children less than five in physicians working
      health centers of primary level in peri-urban areas of Lima, Peru].
AB  - OBJECTIVES: To describe physicians' preferences of antibiotic use in children
      less than 5 years in health centers of primary level in three periurban districts
      in Lima, Peru. MATERIAL AND METHODS: A structured survey was applied to 218
      general practitioners from three health networks of Lima. The survey included six
      typical clinical cases in children under 5 years with questions about antibiotic
      use: the cases were common cold, pharyngitis, pneumonia, bronchial obstructive
      syndrome, watery diarrhea and dysentery. RESULTS: 81.6% of the physicians
      responded that more than a quarter of the patients they attended were children
      under five years. 15.6% of the general physicians would use an antibiotic for
      common cold treatment. For dysentery treatment 90.4% would use antibiotics, the
      frequently used were Trimethoprim-Sulfamethoxazole (TMP-SMX) and Furazolidone.
      86.2% of physicians would recommend an antibiotic for pharyngitis. In a watery
      diarrhea case 32.7% of the doctors would use. In the case of bronchospasm, 73% of
      the doctors would recommend an antibiotic. 96.3% would recommend antibiotics for
      pneumonia. The perception of the degree of mother's satisfaction increased the
      risk of inappropriate prescription of antibiotics OR: 1.6, p=0.031, 95% CI: 1.1
      2.6). CONCLUSIONS: There is tendency to overuse antibiotics for diagnoses such as
      pharyngitis and bronchospasm, as well as in cases of watery diarrhea and common
      cold, the reason could be that a large number of children under five years are
      treated by general practitioners without training in pediatric care.

PMID- 23949501
TI  - [Design and validation of a scale to assess Latin American medical students'
      perception on the labour of the first level of health care].
AB  - OBJECTIVES: To design and validate a scale to assess Latin American medical
      students' perception on first level of health care (FLHC). MATERIALS AND METHODS:
      An observational, analytic and multicentre study was carried out in two phases:
      i) A self-administered questionnaire regarding perceptions on FLHClabor was
      designed. ii) This questionnaire was applied to to medical students from 18
      universities of eight Spanish-speaking Latin American countries. An exploratory
      factor analysis (EFA) was performed through a principal components analysis with
      orthogonal varimax rotation. Sample adequacy was evaluated. Factor extraction was
      based on Kaiser's criteria, Cattell's Scree test and the explained variance
      (>5%). Internal consistency was measured with Cronbach's alpha. RESULTS: 423
      students were included in the analysis; 53.4% were from Peruvian universities.
      After the EFA, the questionnaire conserved 11 items, which were distributed in
      three domains, that explaining together 55.47% of the total variance: i)
      Perceptions concerning the FLHC physician; ii) Perceptions concerning the FiLC
      labor and iii) Perceptions about the economic consequences of working in FLHC.
      CONCLUSION: The scale is composed by three domains and can be used to assess the
      perceptions of the medical work on first level of health care of Spanish-speaking
      Latin American medical students.

PMID- 23949502
TI  - [Proposal of anti-tuberculosis regimens based on susceptibility to isoniazid and
      rifampicin].
AB  - OBJECTIVE: To elaborate optimal anti-tuberculosis regimens following drug
      susceptibility testing (DST) to isoniazid (H) and rifampicin (R). DESIGN: 12 311
      M. tuberculosis strains (National Health Institute of Peru 2007-2009) were
      classified in four groups according H and R resistance. In each group the
      sensitivity to ethambutol (E), pirazinamide (Z), streptomycin (S), kanamycin
      (Km), capreomycin (Cm), ciprofloxacin (Cfx), ethionamide (Eto), cicloserine (Cs)
      and p-amino salicilic acid (PAS) was determined. Based on resistance profiles,
      domestic costs, and following WHO guidelines, we elaborated and selected optimal
      putative regimens for each group. The potential efficacy (PE) variable was
      defined as the proportion of strains sensitive to at least three or four drugs
      for each regimen evaluated. RESULTS: Selected regimes with the lowest cost, and
      highest PE of containing 3 and 4 effective drugs for TB sensitive to H and R
      were: HRZ (99,5%) and HREZ (99,1%), respectively; RZECfx (PE=98,9%) and RZECfxKm
      (PE=97,7%) for TB resistant to H; HZECfx (96,8%) and HZECfxKm (95,4%) for TB
      resistant to R; and EZCfxKmEtoCs (82.9%) for MDR-TB. CONCLUSION: Based on
      resistance to H and R it was possible to select anti-tuberculosis regimens with
      high probability of success. This proposal is a feasible alternative to tackle
      tuberculosis in Peru where the access to rapid DST to H and R is improving
      progressively.

PMID- 23949503
TI  - [Cardiovascular risk factors prevalence among patients with dyslipidemia in
      Colombia].
AB  - OBJECTIVES: To determine the prevalence of cardiovascular risk factors and the
      ten years risk of cardio-cerebrovascular event in patients with dyslipidemia who
      were affiliated to the Colombian health system. MATERIALS AND METHODS: A
      retrospective study was carried out in a random and stratified sample of 551
      patients with dyslipidemia, from a population of 41,201 people with lipid
      lowering therapy in ten Colombian cities between January 1, 2010 and June 30,
      2011. Sociodemographic, anthropometric and biochemical variables were taken from
      medical records, as well as risk factors. To establish the 10-year cardiovascular
      risk was used Framingham algorithm. RESULTS: 311 patients were included, 56.4% of
      them were women, mean age 64.9 +/- 10.8 years. The mean probability of developing
      a cardiovascular event at 10 years was 14%. Other cardiovascular risk factors
      found were hypertension (93.2%), male older than 55 years (35.8%), women older
      than 65 years (28.1%), diabetes mellitus (28.5%), family history of coronary
      heart disease (17.2%), personal history of heart disease or stroke (16.7%) and
      smoking (6.4%). The types of dyslipidemia by frequency were: mixed (46.6%),
      isolated hypercholesterolemia (29.4%) and hypertriglyceridaemia (20.3%).
      CONCLUSIONS: Patients were men and women older than 65 years, mainly suffering
      mixed dyslipidemia, and have a 14.0% probability of suffering a cardiovascular
      event in the next 10 years. It should promote healthy public policies to reduce
      the presence of hypertension and diabetes mellitus.

PMID- 23949504
TI  - [Psychometric assessment and development of a shorter version of a new anxiety
      scale in a hospital sample from Lima, Peru].
AB  - OBJECTIVES: To assess psychometric properties and to develop a shorter version of
      a new anxiety scale. MATERIALS AND METHODS: The 130-item new anxiety scale (NAS
      130) was administered to 254 psychiatric outpatients of a general hospital in
      Lima, Peru. A categorical principal component analysis (CATPCA) was performed
      with the 130 items and based on these results and the relation of each item with
      a Clinical Global Impressions Severity Scale for anxiety (CGI-S) the scale was
      simplified. In addition, the CGI-S was used to assess the concurrent validity of
      the scale. RESULTS: The NAS-130 had a Cronbach's alpha of 0.97 and a Spearman
      correlation coefficient (Rho) with CGI-S of 0.44 (p<0.01). After item selection,
      a 72-item scale was obtained (NAS-72) which had a Cronbach's alpha of 0.96 and a
      Rho with CGI-S of 0.47 (p<0.01). All items of NAS-72 had saturation coefficients
      greater than 0.4 in one dimension according to the CATPCA. NAS-130 and NAS-72
      scores were significantly higher in women than in men (p<0.01). CONCLUSIONS: The
      NAS-72 has psychometric characteristics that suggest that it could be useful to
      measure anxiety in our population; however, the scores should be interpreted
      differently in men and women.

PMID- 23949505
TI  - [Poor coverage insurance in medical graduates for the service rural and urban
      marginal in Peru].
AB  - The aim of this study was to meet the health insurance coverage received by
      recent graduates of universities in Lima during the Service Rural and Urban
      Marginal in Health (SERUMS) during 2012-2013. 290 physicians were included. Data
      of the physicians' insurance to the social health Insurance (EsSalud) were
      reviewed monthly. 6.6% of physicians had been activated his insurance at the end
      of the third month of the beginning of his service. Differences between
      physicians who worked for the Ministry of Health (p<0.01), by gender (p=0.03) and
      if the locale was considered extremely poor (p=0.02) were found. We conclude that
      there is an deficient insurance coverage for the physicians who realize primary
      health care during the SERUMS exercise. 

PMID- 23949506
TI  - [Lead in umbilical cord blood of neonates born in northern Lima].
AB  - The aim of this study was to describe the concentration of lead in umbilical cord
      blood (UCB) of neonates born from primiparous women who live in northern Lima. A
      cross sectional study was carried out at Cayetano Heredia National Hospital, from
      July 2011 to January 2012. 100 neonates born from primiparous women who lived in
      northern Lima in the previous 5 years or more were included. Umbilical cord lead
      levels were measured by the atomic adsorption method, and the demographic
      information and risk factors of the neonates were filled in a patient record
      designed to this purpose. 30% of the neonates had concentration of lead in UCB
      that was considered as increased risk (= 3,0 ug/dL), 16% of the cases had had
      toxic concentration of lead in UCB (= 5 ug/dL). We conclude that there are a high
      percentage of neonates contaminated with lead in the northern Lima. 

PMID- 23949507
TI  - [Evaluation of the impact of multiple micronutrient powders on children anemia in
      three Andean regiones in Peru].
AB  - The aim of this research was to determine the impact of the strategy of multi
      micronutrient supplementation (MMN) on the childhood anemia in three Andean
      regions of Peru. A sentinel surveillance system was established in 29 health
      centers of Andahuaylas, Ayacucho and Huancavelica (Peru) to monitor a cohort of
      children of 6 to 35 months of age whom been received MMM for a period of 12
      months. Data regarding hemoglobin levels were gathered at the beginning and at
      the end of the research; they included consumption of MMN, and other data from
      clinical records and from growth and development charts. Between the child who
      completed the supplementation, the prevalence of anemia decreased from 70.2% to
      36.6% (p value <0.01). 55,0% and 69,1% of children with mild and moderate anemia
      at the beginning of the supplementation got cured. This research shows that
      supplementation with MMN could be a valuable strategy to fight anemia. 

PMID- 23949508
TI  - [Reference intervals for peripheral blood lymphocyte subsets in healthy adults in
      Lima, Peru].
AB  - In order to establish the reference intervals (RIs) of peripheral blood
      lymphocyte subsets (PBL) in healthy adults in Lima (Peru), a cross-sectional
      study was conducted among blood donors taken in between 2011 and 2012. Based on
      the criteria obtained from the guidelines of the Clinical and Laboratory
      Standards Institute (CLSI C28-A3), 318 samples were processed, 61.9% (197/318)
      coming from male donors. For PBL count, a flow cytometer with a simple platform
      was used. The RIs are established for each PBL in adults based on sex with their
      respective reference limits and 90% confidence intervals. Differences were found
      in CD3+ percentage counts (p=0.001) and in CD3-CD56+ absolute (p=0.003) and
      percentage counts (p?0.001). The RIs found are different to those described in
      studies conducted in other countries due to the characteristics of the population
      and the study model. 

PMID- 23949509
TI  - [Metalo-beta-lactamases in clinical isolates of Pseudomonas aeruginosa in Lima,
      Peru].
AB  - The aim of this study was to detect and characterize molecularly metallo-beta
      lactamase (MbetaL) in clinical isolates of Pseudomonas aeruginosa. We carry out a
      cross sectional study in six publics hospital in Lima on August 2011. 51 isolates
      of P. aeruginosa resistant to ceftazidime and reduced susceptibility to
      carbapenemes were evaluated.The phenotypic assay was performed using the
      approximation method with substrate disks (ceftazidime, imipenem and meropenem)
      and ethylenediaminetetraacetic acid (EDTA). MbetaL gene detection was performed
      using the technique of polymerase chain reaction (PCR) multiplex. Through MbetaL
      detected phenotypic method in 15.7% of isolates. Detection of genes revealed the
      presence of the gene in the 8 isolates blaIMP. The first report of MbetaL in P.
      aeruginosa in Peru was described, this should alert the monitoring equipment in
      the institutions to promote control their spread. 

PMID- 23949510
TI  - [Genetic variability of Aedes aegypti determined by mitochondrial gene ND4
      analysis in eleven endemic areas for dengue in Peru].
AB  - In order to establish the genetic variability of Aedes aegypti determined by the
      analysis of the MT-ND4 gene, in eleven endemic regions for dengue in Peru, 51
      samples of Ae. Aegypti were tested. The genetic variability was determined
      through the amplification and sequencing of a fragment of 336 base-pairs of MT
      ND4, the analysis of intra-specific phylogeny was conducted with the Network Ver.
      4.6.10 program; and the phylogenetic analysis, with the Neighbor Joining distance
      method. The presence of five haplotypes of Ae. Aegypti grouped in two lineages
      was identified: the first one includes haplotypes 1, 3 and 5, and the second one
      comprises haplotypes 2 and 4. The geographic distribution of each of the
      haplotypes found is also shown. It is concluded that this variability is caused
      by the active migration of this vector and the human activity-mediated passive
      migration. 

PMID- 23949511
TI  - [Abdominal obesity associated to medical-related absenteeism at a company of
      metal-mechanical industry in Cali, Colombia].
AB  - The aim of this study was examined the abdominal obesity prevalence and
      association with medical-related absenteeism. A cross-sectional study in 185 men
      from the metal-mechanical industry was conducted. Sociodemografic and
      antropometrics data of was gathered, waist circumference was measured as an
      indicator of abdominal obesity. The prevalence of central obesity was 28.7 %.
      Subjects with higher values of central obesity showed higher frequency, higher
      duration and higher costs of medical-related absenteeism, however, this
      relationship was not significant. We conclude that abdominal obesity is highly
      frequent in this sample; however, since it's a reversible risk, enterprises could
      get benefits from preventive and promotional programs destiny to control this
      problem. 

PMID- 23949512
TI  - [Adherence to the recommendations in respiratory rehabilitation of the British
      Thoracic Society in patients with cystic fibrosis: a study of Colombian
      physiotherapists].
AB  - The aim was to evaluate compliance with the recommendations in respiratory
      rehabilitation (ReR), raised by the British Thoracic Society (BTS) in patients
      with cystic fibrosis. A cross-sectional study was conducted in 224 Colombian
      physiotherapists to identify interventions and components of ReR programs as
      recommended by the BTS. Interventions with high level of evidence (Grade A) such
      as: Bronchial Hygiene Therapy (54.0%), and Active Cycle of Breathing Techniques
      (35.3%) were identified. However, high percentage of physiotherapists practiced
      interventions with lower grade of recommendation (Grade D) such as: hypertonic
      saline and bronchodilator to prevent bronchospasm (33.9%), and using manual
      therapy techniques and thoracic mobility exercises (38.4%) to correct postural
      and breathing problems. In conclusions we confirm important differences in
      therapeutic assistant components of the ReR raised by the BTS for patients with
      cystic fibrosis. 

PMID- 23949513
TI  - [Interleukin-1beta, seizures and neuronal cell death].
AB  - Epilepsy is a neurological disorder affecting almost 1% of the world population.
      Experimental human and animal studies suggest that inflammation mediators, like
      cytokines, participate in the physiopathology of epilepsy. Interleukin-1beta (IL
      1beta) could influence susceptibility for seizures, as well as neuronal death
      caused by seizures, although some findings are contradictory. This document
      reviews the current knowledge establishing a connection between IL-1beta,
      seizures and neuronal death. 

PMID- 23949514
TI  - [Addressing the controversy regarding the association between thimerosal
      containing vaccines and autism].
AB  - Vaccination is one of the most important public health interventions in the
      reduction childhood morbidity and mortality. Thimerosal is an organic mercury
      compound used as preservante in multi-dose vials. Often in Peru, there are waves
      of controversy about the safety of this type of vaccines, mainly arguing that
      there is an association between them and autism. As a result of these
      controversies, there have been some voices asking for laws banning thimerosal
      containing vaccines, which would have a large impact in costs and the logistic
      aspects of the public vaccination programs. The aim of this article is to review
      the literature for the main controversies about thimerosal in vaccines and its
      supposed association to autism. We made an historical review about these
      controversies given the available scientific evidence and the statements from
      important international organizations. We concluded that the current available
      evidence do not support an association between thimerosal and childhood
      neurodevelopmental disorders, such as autism. 

PMID- 23949515
TI  - [Interventions to control overweight and obesity in children and adolescents in
      Peru].
AB  - Overweight and obesity in children and adolescents represent a serious public
      health problem in Peru, with high costs for society that require the
      implementation of a set of public policies directed toward its control. Thus,
      interventions have been proposed as the regulation of advertising of unhealthy
      foods, self-regulation, the implementation of kiosks healthy and nutritional
      labeling. From the analysis of the problem of overweight and obesity in children
      and adolescents in Peru, this article is a narrative review of such
      interventions. 

PMID- 23949516
TI  - [What a primary health care is: some considerations after almost thirty five
      years of Alma-Ata].
AB  - Primary health care was conceived in the 70s as a comprehensive, joint and
      inclusive strategy to achieve the goal of "Health for Everyone". It was the
      result of important social, political and economic changes which occurred at
      global level back in those years and which persist until now. Due to an
      unfortunate combination of words, Primary Healthcare has been mistakenly
      understood by many as "healthcare at the basic level" or the "provision of basic,
      and hence insufficient services to the poorest", wrong concepts that contribute
      to the current social and health inequalities. This article explains what primary
      healthcare is and what it is not in order to address the subject in its real
      context.

PMID- 23949517
TI  - [Sociopolitical determinants of international health policies].
AB  - For decades, two opposing logics dominate the health policy debate: A
      comprehensive health care approach, with the 1978 Alma Ata Declaration as its
      cornerstone, and private competition logic, emphasizing the role of the private
      sector. We present this debate and its influence on international health policies
      in the context of changing global economic and sociopolitical power relations.
      The neoliberal approach is illustrated with Chile's health sector reform in the
      1980s and the Colombian reform since 1993. The comprehensive 'public logic' is
      shown through the social insurance models in Costa Rica and in Brazil, and
      through the national public health systems in Cuba since 1959, and in Nicaragua 
      during the 1980s. These experiences emphasize that health (care) systems do not
      naturally gravitate towards greater fairness and efficiency, but that they
      require deliberate policy decisions. 

PMID- 23949518
TI  - [Primary care in the USA and the Peruvian experience in perspective].
AB  - Due to a complex payment system, the health system of the United States is
      fragmented, expensive, and achieves the goal of improving the health of the
      entire population. Excessive health costs increase the budget deficit in the US.
      This situation makes to the government to have greater willingness to try new
      approaches in the delivery of health services. Is well know that the states that
      have a solid system of primary health care (PC), spent less money in diseases and
      have lower utilization of health services (reflected in fewer days of
      hospitalization). This is why the AP is spreading in the US making doctors,
      nurses and other providers to collaborate on new proposals for team-based care,
      coordinated and patient-oriented generating real benefits while controlling
      costs. The US experience with AP support evidence-based approach to propose, from
      a foreign perspective, strengthening the AP in Peru. 

PMID- 23949519
TI  - [Transforming the Peruvian birth information system].
AB  - The On-Line Registration of Certificates of Live Births was developed in
      conjunction with the Ministry of Health of Peru and the National Registry of
      Identification and Civil Status. It is a free system that registers newborns in
      the delivery room itself which generates a real time certificate of live birth.
      This simplifies the procedures required to obtain the birth certificate and the
      National Identity Document for the newborn. This system has been implemented in
      114 health centers in 21 regions from March 2012 to March 2013, and has
      registered 113,917 live births, providing accurate, timely and quality
      information about these births. This system is the main cornerstone of the health
      information system which helps obtain real time statistics for adequate and
      timely decision making in public health.

PMID- 23949520
TI  - [Adjusted clinicals groups: a patient classification system through risk
      adjustment].
AB  - Adjusted Clinical Groups (ACG) are risk adjustment systems that classify people
      according to their age, sex and medical conditions, these people have a similar
      consumption of health resources over a given period of time. They were developed
      by Starfield and Weiner (Johns Hopkins University, USA, 1991), and their
      objective is to measure the degree of illness among patients based on the levels
      of comorbidity. Their main applications are: a) the evaluation of the efficiency
      in the use of health services, b) measurement of population's comorbidity, and c)
      to program the funding or capitation fee for groups of providers. Some of the
      advantages of the ACG system are the limited number of variables needed for each
      patient (age, sex and diagnosis) and the unit of measurement, which is the
      patient. Some characteristics of this population risk adjustment system are
      commented. 

PMID- 23949521
TI  - [Human rights and informed consent in clinical practice: beyond the right to
      health].
AB  - Providing medical care is us a complex process that requires a strict respect for
      human rights. In countries like Peru, despite of having regulations and specific
      laws, patient's autonomy is not a common currency and certainly paternalism and
      beneficence generally overrule in physicians decision making. In this type of
      reality the requirement to health care professionals for respecting fundamental
      rights should be considered crucial, far more than in societies where citizens
      are really empowered. But to achieve the full respect of human rights, especially
      when providing a health care service, there is the need to go much further than
      just advocating for appropriate legislation and regulatory frameworks. In this
      article I argue that the violation of certain rights as the informed consent
      process by health care providers, is rooted in how these professionals, specially
      medical doctors trained in the western tradition, establish priorities and arrive
      to moral judgments. In this scenario I consider the need of a change in the way
      the Human Rights framework is being used to improve fundamental rights respect in
      health care.

PMID- 23949522
TI  - [Safe use of medications among elderly people: a checklist].
AB  - Elderly people are particularly vulnerable to adverse drug reactions (ADR) due to
      polypathology and polypharmacy and the changes in pharmacokinetics and
      pharmacodynamics of medications induced by aging. It is very important to
      evaluate the safety aspects and appropriate use of medications in this
      population. For this purpose, a checklist is proposed consisting of a list of
      medications (including herbal medicine), detecting and treating geriatric
      syndromes induced by medications, overprescription, unprescription and
      underprescription; measuring and treating drug adhesion, measuring parameters for
      geriatric posology, preventing adverse reactions due to inadequate drug recalls,
      evaluating aging people's capacity to take their medications and using the
      minimum datasheet regarding the medication prescribed to the patient. This
      checklist is developed based on validated instruments. It is a proposal which
      application in the outpatient and inpatient context is possible and feasible. 

PMID- 23949523
TI  - [Recurrent diarrhea due to Cystoisopora belli in HIV/AIDS patients receiving
      HAART].
AB  - The Cystoisospora belli, before denominated as Isospora belli, is the etiologic
      agent of cystoisosoporiasis, an opportunistic infection affecting
      immunocompromised patients, characterized by chronic diarrhea and weight loss.
      The incidence of chronic diarrhea for this agent, in HIV patients, has decreased
      considerably. This thanks to the advent of highly active antiretroviral therapy
      (HAART), which has improved the patient's immune response and decrease viral
      load. We present six cases of cystoisosoporiasis recurrent and refractory to
      treatment in HIV patients, who was being treated with with trimethoprim /
      sulfamethoxazole (TMP / SMX) orally as a prophylaxis. Five of these patients
      passed away due to the infection, despite of the fact that they had a good
      response to HAART (adequate increase in CD4 and viral load undetectable) and they
      had been treated with second line drugs. 

PMID- 23949524
TI  - [Kennedy disease in Peru: first cases with molecular diagnosis].
AB  - Kennedy's disease is an X-linked recessive disorder with onset in adulthood,
      characterized by progressive degeneration of spinal motor neurons due to a
      dynamic mutation in the androgen receptor gene. We report three families (five
      cases) characterized by progressive weakness involving both limbs and bulbar
      muscles, atrophy, tremor, cramps and endocrinologic disturbances; the
      neurophysiological studies demonstrated second motor neuron impairment. The
      molecular analysis identified abnormal CAG repeats expansion in the androgen
      receptor gene (AR) in all cases. Clinical features were consistent with other
      previous reports. These are the first Peruvian cases of Kennedy's disease with
      confirmed molecular diagnosis.

PMID- 23949525
TI  - [Runa soncco: Manuel Nunez Butron and his health education project].
AB  - Runa soncco, a Quechua term for "Indian heart", is the title of a magazine
      published between 1935 and 1948, which articles reveal the intention to integrate
      the Andean culture with Western public health on-site. It also turned into a key
      tool for the dissemination of the sanitation and education message and the
      indigenous movement led by Dr. Manuel Nunez Butron, one of the first experiences
      in promotional preventive care in Peru and in the world - a pioneer of what four
      decades later would be called "primary health care". 

PMID- 23949526
TI  - ["Hueseros" wampis: traditional care at a native community of the Peruvian
      Amazon].

PMID- 23949527
TI  - [Rural internship as an approach to primary health care -the experience of a
      university in Cusco, Peru].

PMID- 23949529
TI  - [Public health and primary health care training in medical students: an
      experience in Peru].

PMID- 23949528
TI  - [Primary care doctors' opinion on a risk adjustment system: adjusted clinical
      groups].

PMID- 23949530
TI  - [Inadequate use of inhalers among asma patients who use Salbutamol].

PMID- 23949531
TI  - [Approach to the status of anemia in a pediatric population from a periurban zone
      of Callao, Peru].

PMID- 23949533
TI  - [Isolation of dengue virus serotype 1 and 3 from a coinfected patient using a
      modified shell vial culture].

PMID- 23949532
TI  - [Online buying and selling of thesis: an ethical problem to control].

PMID- 23949534
TI  - [Evaluation of western blot with five hydatid antigens for the diagnosis of human
      echinococcosis].

PMID- 23949535
TI  - [Association of tranexamic acid to mortality and blood transfusion among patients
      with hemoptysis at Hipolito Unanue Hospital of Lima, Peru].

PMID- 23949536
TI  - [Physical performance in older adults living at high altitude].

PMID- 23949538
TI  - [QR code opportunities to spread health-related information].

PMID- 23949537
TI  - [Differences between the promotional weighted average and the National Medical
      Test degree in the process of getting a vacancy for the Rural and Suburban Health
      Service].

PMID- 23949539
TI  - [Patients' participation in clinical decision making as a strategy to protect
      their rights].

PMID- 23949540
TI  - [Squamous cell carcinoma of the bladder in a patient with HIV and paraplegia].
AB  - In patients with spinal cord injury (SCI) the rate of squamous cell carcinomas
      (SCC) among bladder tumors is increased compared to the general population. An
      increased life expectancy is achieved by modern HIV treatment so that more AIDS
      unrelated malignomas, e.g. bladder tumors, occur in these patients. Therefore,
      the risk for SCC in this group of patients is increased in patients with SCI and
      HIV but the combination of these two diseases is rare. We report the first case
      of SCC in a patient with SCI and HIV. Initial symptoms of bladder tumors in
      patients with SCI are often unspecific; therefore, in cases with new onset
      hematuria, recurrent urinary tract infections and changes in bladder function,
      cystoscopy and computed tomography (CT) scanning should be considered. 

PMID- 23949541
TI  - Staff perception of aggressive behaviour in community services for adults with
      intellectual disabilities.
AB  - Experiencing aggressive behaviour has been associated with increased stress and
      turnover among staff who support adults with intellectual disabilities. Incident
      perception is a strong predictor of psychological outcomes after trauma but has
      not been studied in this staff group. This study clustered exposure to aggression
      and endorsement of emotional difficulties among 386 community residential group
      home staff and evaluated the contribution of four behavioural topographies to
      staff-rated perceived severity. Staff exposure varied considerably. Perceived
      severity correlated with subjective emotional difficulties. High perceived
      severity was associated with daily exposure, aggression towards others causing
      injury, and property aggression causing injury or damage. Therefore, the role the
      staff plays, whether a witness or target, may impact their experience. 

PMID- 23949542
TI  - Report on the 2nd Annual Infinium Humanmethylation450 Array Workshop: 15 April
      2013 QMUL, London, UK.
AB  - The Illumina Infinium HumanMethylation450 BeadChip - the successor to their
      hugely popular HumanMethylation27 BeadChip - is arguably the most prevalent
      platform for large-scale studies of DNA methylome analysis. After the success of
      last year's meeting (1) that discussed initial analysis strategies for this then
      new platform, this year's meeting (held at Queen Mary, University of London)
      included the presentation of now established pipelines and normalization methods
      for data analysis, as well as some exciting tools for down-stream analysis. The
      importance of defining cell composition was a new topic mentioned by most
      speakers. The epigenome varies between cell types and insuring that methylation
      differences are related to sample treatment and not a differing cell population
      is essential. The meeting was attended by 215 computational and bench scientists
      from 18 countries. There were 11 speakers, a small poster session, and a
      discussion session. Talks were recorded and are now freely available at
      http://www.illumina.com/applications/epigenetics/array
      based_methylation_analysis/methylation-array-analysis-education.ilmn. 

PMID- 23949545
TI  - Re: Willemink MJ, van Es HW, Helmhout PH, et al. The effects of dynamic isolated
      lumbar extensor training on lumbar multifidus functional cross-sectional area and
      functional status of patients with chronic non specific low back pain. Spine
      2012;37: E1651-8.

PMID- 23949543
TI  - Spatiotemporal signalling in plant development.
AB  - Plants, being sessile organisms, need to respond to changing environments, and as
      a result they have evolved unique signalling mechanisms that allow rapid
      communication between different parts of the plant. The signalling mechanisms
      that direct plant development include long-range effectors, such as
      phytohormones, and molecules with a local intra-organ range, such as peptides,
      transcription factors and some small RNAs. In this Review, we highlight recent
      advances in understanding plant signalling mechanisms and discuss how different
      classes of signalling networks can integrate with gene regulatory networks and
      contribute to plant development. In some cases, we also address the evolutionary
      context of mechanisms and discuss possible links between the lifestyle of plants
      and selection for different signalling mechanisms. 

PMID- 23949544
TI  - New genes as drivers of phenotypic evolution.
AB  - During the course of evolution, genomes acquire novel genetic elements as sources
      of functional and phenotypic diversity, including new genes that originated in
      recent evolution. In the past few years, substantial progress has been made in
      understanding the evolution and phenotypic effects of new genes. In particular,
      an emerging picture is that new genes, despite being present in the genomes of
      only a subset of species, can rapidly evolve indispensable roles in fundamental
      biological processes, including development, reproduction, brain function and
      behaviour. The molecular underpinnings of how new genes can develop these roles
      are starting to be characterized. These recent discoveries yield fresh insights
      into our broad understanding of biological diversity at refined resolution. 

PMID- 23949547
TI  - Prognostic value of preoperative 18F-FDG PET/CT for primary head and neck
      squamous cell carcinoma.
AB  - (18)F-FDG PET/CT is clinically useful in the initial staging and follow-up of
      patients with head and neck squamous cell carcinoma (HNSCC). We studied the
      potential prognostic significance of preoperative (18)F-FDG PET/CT in HNSCC. The
      medical records of 294 patients who underwent preoperative (18)F-FDG PET/CT for
      HNSCC were retrospectively reviewed. The median SUVmax of the primary lesions
      (SUVmax-p) and cervical lymph nodes (SUVmax-n) was 7.98 +/- 5.04 (range 1.2-28.7)
      and 3.34 +/- 3.70 (range 1.0-20.4), respectively. There was a significant
      difference between with and without recurrence in SUVmax-p (11.14 +/- 5.36 vs.
      6.78 +/- 4.35, p < 0.001) and SUVmax-n (5.60 +/- 4.22 vs. 1.75 +/- 1.46, p <
      0.001). The cut-off values of SUVmax-p and SUVmax-n in the context of recurrence
      and cancer-related death were 8.5 and 3.5. The 5-year disease-free survival of
      patients with SUVmax-p < 8.5 and SUVmax-n < 3.5 was 79 and 79%, respectively,
      whereas that of patients with SUVmax-p >= 8.5 and SUVmax-n >= 3.5 was 39 and 30
      %, respectively. Multivariate analysis confirmed the significant association
      between 5-year disease-free survival and SUVmax-p >= 8.5 (hazard ratio (HR) 2.68,
      p < 0.001) and SUVmax-n >= 3.5 (HR 2.29, p = 0.007). Furthermore, SUVmax-p >= 8.5
      (HR 3.20, p = 0.012) and SUVmax-n >= 3.5 (HR 2.14, p < 0.001) were associated
      with 5-year overall survival. (18)F-FDG PET/CT cut-off values of SUVmax-p >= 8.5
      or SUVmax-n >= 3.5 are associated with a recurrence and survival in HNSCC.

PMID- 23949548
TI  - One-stop endoscopic hernia surgery: efficient and satisfactory.
AB  - BACKGROUND: One-stop surgery offers patients diagnostic work-up and subsequent
      surgical treatment on the same day. In the present study, patient satisfaction
      and efficiency from an institutional perspective were evaluated in patients who
      were referred for one-stop endoscopic inguinal hernia repair. METHOD: In a high
      volume inguinal hernia clinic, all consecutive patients referred for one-stop
      surgical treatment, were registered prospectively. An instructed secretary
      screened patients for eligibility for the one-stop option when the appointment
      was made. Totally extraperitoneal hernia repair under general anaesthesia was the
      preferred operative technique. Patient's satisfaction, successful day surgery and
      institutional efficiency were evaluated. RESULTS: Between January 2010 and
      January 2012 a total of 349 patients (17 % of all patients in the hernia clinic)
      were referred for one-stop hernia repair. Mean age was 47.5 years and 96.3 % were
      males. Three hundred thirty-six patients underwent hernia surgery on the same day
      (96.3 %). In thirteen patients (3.7 %) no operative repair was done on the day of
      presentation due to an incorrect diagnosis (n = 7), a watchful waiting policy for
      asymptomatic hernia (n = 3), rescheduling due to a large scrotal hernia, and
      there were two "no shows". Following hernia repair 97 % of the patients were
      discharged on the same day, while ten patients required hospitalization. Based on
      the questionnaires the main satisfaction score among patients was 9.0 (8.89-9.17
      95 % CI) on a scale ranging from 0 to 10. CONCLUSION: One-stop hernia surgery is
      feasible and satisfactory from an institutional as well as from a patient's
      perspective.

PMID- 23949549
TI  - "Rescue administration" of intracoronary thrombolytic therapy for drug-eluting
      stent thrombosis.
AB  - Stent thrombosis is an example of device-induced, platelet-mediated arterial
      thrombosis with a potentially fatal adverse event that often leads to myocardial
      infarction and/or death. The optimal treatment of patients with drug-eluting
      stent thrombosis in whom mechanical thrombectomy has failed is not established.
      This case demonstrates the usefulness of intracoronary thrombolysis after failed
      mechanical thrombectomy in patients with stent thrombosis. To our knowledge, this
      is the first report on using intracoronary thrombolysis in this specific
      situation. 

PMID- 23949550
TI  - QRS fragmentation in acquired long QT syndrome does not always predict torsades
      of pointes tachycardia: a case report.

PMID- 23949551
TI  - Cor triatriatum sinister and cryptogenic stroke.

PMID- 23949552
TI  - Asymptomatic giant pericardial cyst mimicking dextrocardia on chest X-ray.

PMID- 23949553
TI  - Endovascular management for retreatment of postsurgical intracranial aneurysms.
AB  - INTRODUCTION: Incomplete surgical treatment of intracranial aneurysms and
      recurrent postsurgical aneurysms are associated with a risk of rebleeding, and
      additional treatment is generally recommended. Surgical retreatment may carry a
      risk of procedural complications due to technical difficulty. We present here our
      experience with the endovascular approach for the retreatment of intracranial
      aneurysms that were initially treated with open surgery. METHODS: From January
      2002 through January 2013, a total of 43 patients with 43 postsurgical index
      aneurysms were identified and underwent subsequent endovascular treatment.
      Clinical and radiological data were retrospectively reviewed. RESULTS: Thirty-one
      patients were surgically clipped before endovascular coiling and 12 patients were
      nonclipped, which included wrapping. Hemorrhagic presentation occurred in 21
      patients prior to coiling. The interval between the initial surgical treatment
      and coiling varied from 0 days to 264 months (median, 9 months). Endovascular
      coiling resulted in the successful occlusion of 36 aneurysms (84 %). Procedure
      related complications included asymptomatic thrombus formation in six patients,
      symptomatic cerebral infarction in two patients, and retroperitoneal hemorrhage
      in one patient. Delayed cerebral infarction occurred in two patients with a
      deployed stent. The procedure-related permanent morbidity and mortality rates
      were 6.9 and 0 %, respectively. Radiological follow-up evaluations beyond 6
      months were available in 26 patients (60 %), which revealed major recanalization
      in three patients (11.5 %). There was no rebleeding during the follow-up period,
      which ranged from 3 to 115 months (mean, 34.5 months). CONCLUSION: Endovascular
      embolization may serve as a safe, efficacious, and durable treatment option in
      the management of postsurgical intracranial aneurysms.

PMID- 23949554
TI  - Prostate cancer metastasis to the stomach: 9 years after the initial diagnosis-
      case report and a literature review.

PMID- 23949556
TI  - Intra-abdominal desmoplastic small round cell tumor mimicking gastrointestinal
      stromal tumor.

PMID- 23949555
TI  - Cancer stem cells biomarkers in gastric carcinogenesis.
AB  - BACKGROUND: Gastric carcinogenesis is a multistep process, involving multiple
      molecular alterations, including changes in cancer stem cells (CSCs). The present
      investigation was undertaken to determine whether changes in cancer stem cells
      could be utilized as a marker of progression of gastric carcinogenesis by
      examining the expression of gastric CSCs at different stages of carcinogenesis.
      METHODS: Ninety-three cases with 31 in each group of chronic superficial
      gastritis (CSG), chronic atrophic gastritis (CAG), or gastric cancer (GC) were
      analyzed immunohistochemically for proliferating cell nuclear antigen (PCNA) and
      Bcl-xl as biomarkers of proliferation and apoptosis, respectively, and CD44,
      CD166, and LGR5 levels by qRT-PCR as markers of gastric CSCs. Additionally, the
      levels of P53 and phosphorylated form of epidermal growth factor receptor (p
      EGFR) were examined. RESULTS: While the levels of each of these biomarkers were
      found to be low to moderate in CSG and CAG patients, they were markedly increased
      in GC patients, in whom co-expression of CD44 with LGR5 and CD166 with p-EGFR was
      found to be the highest. We have also observed that although the expression of
      different CSC markers as well as the levels of p-EGFR were increased in
      precancerous lesions (CSG and CAG), they are further augmented in GC suggesting
      that they may play a pivotal role in the development and progression of gastric
      cancer. CONCLUSIONS: Our observations suggest that the progression to gastric
      carcinogenesis from preneoplastic lesions such as superficial gastritis and
      chronic atrophic gastritis is associated with induction of CSCs together with
      increase in cell proliferation and inhibition of apoptosis.

PMID- 23949557
TI  - Does diffusion tensor tractography of the corticospinal tract correctly reflect
      motor function?
AB  - OBJECTIVE: To investigate the consistency of diffusion tensor tractography of the
      corticospinal tract on motor function. CLINICAL PRESENTATIONS AND INTERVENTION:
      Three patients with brain tumor were admitted to our hospital with impaired motor
      function. Diffusion tensor imaging (DTI) and tractography were performed in these
      patients to assess their affected corticospinal tract. The corticospinal tract
      showed interruption with moderately impaired motor function in 2 patients. The
      third case had significantly weakened muscle strength on the left upper limb but
      an intact right corticospinal tract. CONCLUSION: These cases showed that the
      corticospinal tracts obtained by DTI with tractography were inconsistent with
      motor function. Hence, DTI should be interpreted with caution.

PMID- 23949558
TI  - Stratified patient-centered care in type 2 diabetes: a cluster-randomized,
      controlled clinical trial of effectiveness and cost-effectiveness.
AB  - OBJECTIVE: Diabetes treatment should be effective and cost-effective. HbA1c
      associated complications are costly. Would patient-centered care be more (cost-)
      effective if it was targeted to patients within specific HbA1c ranges? RESEARCH
      DESIGN AND METHODS: This prospective, cluster-randomized, controlled trial
      involved 13 hospitals (clusters) in the Netherlands and 506 patients with type 2
      diabetes randomized to patient-centered (n=237) or usual care (controls) (n=269).
      Primary outcomes were change in HbA1c and quality-adjusted life years (QALYs);
      costs and incremental costs (USD) after 1 year were secondary outcomes. We
      applied nonparametric bootstrapping and probabilistic modeling over a lifetime
      using a validated Dutch model. The baseline HbA1c strata were <7.0% (53
      mmol/mol), 7.0-8.5%, and >8.5% (69 mmol/mol). RESULTS: Patient-centered care was
      most effective and cost-effective in those with baseline HbA1c>8.5% (69
      mmol/mol). After 1 year, the HbA1c reduction was 0.83% (95% CI 0.81-0.84%) (6.7
      mmol/mol [6.5-6.8]), and the incremental cost-effectiveness ratio (ICER) was 261
      USD (235-288) per QALY. Over a lifetime, 0.54 QALYs (0.30-0.78) were gained at a
      cost of 3,482 USD (2,706-4,258); ICER 6,443 USD/QALY (3,199-9,686). For baseline
      HbA1c 7.0-8.5% (53-69 mmol/mol), 0.24 QALY (0.07-0.41) was gained at a cost of
      4,731 USD (4,259-5,205); ICER 20,086 USD (5,979-34,193). Care was not cost
      effective for patients at a baseline HbA1c<7.0% (53 mmol/mol). CONCLUSIONS:
      Patient-centered care is more valuable when targeted to patients with HbA1c>8.5%
      (69 mmol/mol), confirming clinical intuition. The findings support treatment in
      those with baseline HbA1c 7-8.5% (53-69 mmol/mol) and demonstrate little to no
      benefit among those with HbA1c<7% (53 mmol/mol). Further studies should assess
      different HbA1c strata and additional risk profiles to account for heterogeneity
      among patients.

PMID- 23949559
TI  - Risk of breast cancer by individual insulin use: an international multicenter
      study.
AB  - OBJECTIVE Several studies have been published in 2009 suggesting a possible
      association between insulin glargine and increased risk of malignancies,
      including breast cancer. The objective of this study was to assess the relation
      between the individual insulins (glargine, aspart, lispro, and human insulin) and
      development of breast cancer. RESEARCH DESIGN AND METHODS Seven hundred seventy
      five incident cases of primary invasive or in situ carcinoma breast cancer
      occurring in women with diabetes from 92 centers in the U.K., Canada, and France
      were matched to a mean of 3.9 diabetic community control subjects (n = 3,050;
      recruited from 580 general practices) by country, age, recruitment date, and
      diabetes type and management. The main risk model was a multivariate conditional
      logistic regression model with case/control status as the dependent variable and
      individual insulin use, 8 years preceding the index date, as the independent
      variable, controlling for past use of any insulin, oral antidiabetes drugs,
      reproductive factors, lifestyle, education, hormone replacement therapy and
      history of contraceptive use, BMI, comorbidities, diabetes duration, and annual
      number of physician visits. Glargine was also compared with every other insulin
      by computing all ratios using the variance-covariance matrix of logistic model
      parameters. RESULTS Adjusted odds ratios of breast cancer for each type of
      insulin versus no use of that insulin were 1.04 (95% CI 0.76-1.44) for glargine,
      1.23 (0.79-1.92) for lispro, 0.95 (0.64-1.40) for aspart, and 0.81 (0.55-1.20)
      for human insulin. Two-by-two comparisons found no difference between glargine
      and the different types of insulins. Insulin dosage or duration of use and tumor
      stage did not change the results. CONCLUSIONS This international study found no
      difference in the risk of developing breast cancer in patients with diabetes
      among the different types of insulin with short- to mid-term duration of use.
      Longer-term studies would be of interest. 

PMID- 23949560
TI  - Differential associations of oral glucose tolerance test-derived measures of
      insulin sensitivity and pancreatic beta-cell function with coronary artery
      calcification and microalbuminuria in type 2 diabetes.
AB  - OBJECTIVE We evaluated relationships of oral glucose tolerance testing (OGTT)
      derived measures of insulin sensitivity and pancreatic beta-cell function with
      indices of diabetes complications in a cross-sectional study of patients with
      type 2 diabetes who are free of overt cardiovascular or renal disease. RESEARCH
      DESIGN AND METHODS A subset of participants from the Penn Diabetes Heart Study (n
      = 672; mean age 59 +/- 8 years; 67% male; 60% Caucasian) underwent a standard 2
      h, 75-g OGTT. Insulin sensitivity was estimated using the Matsuda Insulin
      Sensitivity Index (ISI), and beta-cell function was estimated using the
      Insulinogenic Index. Multivariable modeling was used to analyze associations
      between quartiles of each index with coronary artery calcification (CAC) and
      microalbuminuria. RESULTS The Insulinogenic Index and Matsuda ISI had distinct
      associations with cardiometabolic risk factors. The top quartile of the Matsuda
      ISI had a negative association with CAC that remained significant after adjusting
      for traditional cardiovascular risk factors (Tobit ratio -0.78 [95% CI -1.51 to 
      0.05]; P = 0.035), but the Insulinogenic Index was not associated with CAC.
      Conversely, the highest quartile of the Insulinogenic Index, but not the Matsuda
      ISI, was associated with lower odds of microalbuminuria (OR 0.52 [95% CI 0.30
      0.91]; P = 0.022); however, this association was attenuated in models that
      included duration of diabetes. CONCLUSIONS Lower beta-cell function is associated
      with microalbuminuria, a microvascular complication, while impaired insulin
      sensitivity is associated with higher CAC, a predictor of macrovascular
      complications. Despite these pathophysiological insights, the Matsuda ISI and
      Insulinogenic Index are unlikely to be translated into clinical use in type 2
      diabetes beyond established clinical variables, such as obesity or duration of
      diabetes. 

PMID- 23949561
TI  - Chronic fatigue in type 1 diabetes: highly prevalent but not explained by
      hyperglycemia or glucose variability.
AB  - OBJECTIVE Fatigue is a classical symptom of hyperglycemia, but the relationship
      between chronic fatigue and diabetes has not been systematically studied. We
      investigated prevalence, impact, and potential determinants of chronic fatigue in
      patients with type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS Out of
      324 randomly selected T1DM outpatients, 214 participated in this cross-sectional
      observational study. Participants were compared with age- and sex-matched
      population-based controls. Chronic fatigue, functional impairments, current
      health status, comorbidity, diabetes-related factors, and fatigue-related
      cognitions and behaviors were assessed with questionnaires, and HbA1c values and
      comorbidity were assessed with medical records. Sixty-six patients underwent
      continuous glucose monitoring combined with an electronic fatigue diary for 5
      days. Acute fatigue and four glucose parameters were determined: mean,
      variability, and relative time spent in hypoglycemia and hyperglycemia. RESULTS
      T1DM patients were significantly more often chronically fatigued (40%; 95% CI 34
      47%) compared with matched controls (7%; 95% CI 3-10%; P < 0.001). Chronically
      fatigued patients had significantly more functional impairments. Fatigue was the
      most troublesome symptom. Age, depression, pain, sleeping problems, low self
      efficacy concerning fatigue, and physical inactivity were significantly
      associated with chronic fatigue. Chronically fatigued patients spent slightly
      less time in hypoglycemia (proportion 0.07 +/- 0.06 vs. 0.12 +/- 0.10; P =
      0.025). Glucose parameters were not related to acute fatigue. CONCLUSIONS Chronic
      fatigue is highly prevalent and clinically relevant in T1DM. Its significant
      relationship with cognitive behavioral variables and weak association with blood
      glucose levels suggests that behavioral interventions could be helpful in
      managing chronic fatigue in T1DM. 

PMID- 23949562
TI  - Risk of metabolic syndrome and diabetes among young twins and singletons in
      Guinea-Bissau.
AB  - OBJECTIVE: Twins in Africa may be at increased risk of metabolic disorders due to
      strained conditions in utero, including high exposure to infections. We studied
      metabolic syndrome (MS) and diabetes mellitus (DM) among young twins and
      singletons in Guinea-Bissau. RESEARCH DESIGN AND METHODS: The study was cross
      sectional and occurred from October 2009 until August 2011 at the Bandim Health
      Project, a demographic surveillance site in the capital Bissau. Twins and
      singleton controls between 5 and 32 years were visited at home. Fasting blood
      samples for metabolic measurements were collected. Zygosity was established
      genetically for a subset. DM was defined as HbA1c >=6.5% (48 mmol/mol) and MS by
      the International Diabetes Federation criteria. RESULTS: HbA1c was available for
      574 twins and 463 singletons. Mean age was 15.3 years versus 15.8 years,
      respectively. Eighteen percent of twins were monozygotic. There were no DM cases
      among twins but one among singletons. A total of 1.4% (8 of 574) of twins had
      elevated HbA1c (6.0-6.4%, 42-46 mmol/mol) compared with 2.4% (11 of 463) of
      singletons (P = 0.28). Mean HbA1c was 5.3% (34 mmol/mol) for both groups. MS data
      were available for 364 twins and 360 singletons. The MS prevalence was 3.0% (11
      of 364) among twins and 3.6% (13 of 360) among singletons (P = 0.66). The
      prevalence of fasting blood glucose (F-glucose) >=5.6 mmol/L was 34.9% (127 of
      364) for twins versus 24.7% (89 of 360) for singletons (P = 0.003). Median
      homeostasis model assessment-insulin resistance did not differ (P = 0.34).
      CONCLUSIONS: The MS and DM prevalences among young individuals in Guinea-Bissau
      were low. Twins did not have a higher MS and DM burden than singletons, though
      elevated F-glucose was more common among twins.

PMID- 23949563
TI  - Low-volume morning-only polyethylene glycol with specially designed test meals
      versus standard-volume split-dose polyethylene glycol with standard diet for
      colonoscopy: a prospective, randomized trial.
AB  - BACKGROUND/AIMS: Split-dose polyethylene glycol (PEG) is a standard bowel
      preparation regimen for colonoscopy, but the large volume is burdensome to ingest
      and the night dose causes sleep disturbance. This study was performed to evaluate
      the efficacy and tolerability of a bowel preparation protocol using low-volume
      morning-only PEG with specially designed low-residue test meals (LV-PEG with TM)
      compared to a standard-volume split-dose PEG bowel preparation with a standard
      diet (SV-PEG with SD). METHODS: This was a single-center, prospective,
      randomized, investigator-blinded, noninferiority study. The primary end point was
      bowel preparation quality according to the Ottawa scale. Tolerability,
      compliance, adverse events, sleep quality and polyp/adenoma detection were also
      assessed. RESULTS: Among 197 patients analyzed (mean age 54.6 years, 51.3% men),
      97 received LV-PEG with TM and 100 received SV-PEG with SD. The Ottawa score for
      the total colon was 3.76 +/- 2.07 in the LV-PEG with TM group and 3.67 +/- 1.57
      in the SV-PEG with SD group (p = 0.723; difference 0.09, 95% confidence interval 
      0.60 to 0.42). The compliance was high (more than 95%) in both groups (p =
      0.621). PEG was easier to ingest for patients in the LV-PEG with TM group
      compared to the SV-PEG with SD group [visual analogue scale (VAS) for difficulty:
      4.64 +/- 2.46 vs. 5.97 +/- 2.42, respectively; p < 0.001]. Diet instructions were
      also easier to comply with for patients in the LV-PEG with TM group compared to
      the SV-PEG with SD group (VAS for difficulty: 3.11 +/- 2.25 vs. 4.00 +/- 2.39,
      respectively; p = 0.008). Patients in the LV-PEG with TM group had a lower
      incidence of abdominal bloating (p = 0.012) and better sleep quality (p < 0.001).
      There was no difference between the groups regarding polyp and adenoma detection.
      CONCLUSIONS: LV-PEG with TM and SV-PEG with SD have similar efficacy with regard
      to bowel preparation for colonoscopy. LV-PEG with TM provided easier PEG intake
      and diet compliance, less abdominal bloating and better sleep quality than SV-PEG
      with SD.

PMID- 23949564
TI  - Percutaneous injection of autologous, culture-expanded mesenchymal stem cells
      into carpometacarpal hand joints: a case series with an untreated comparison
      group.
AB  - In the present study, we describe six patients who received autologous
      mesenchymal stem cell (MSC) therapy for symptomatic carpometacarpal (CMC) joint
      and hand osteoarthritis (OA). Six patients who received injections of adult
      autologous culture expanded MSCs in their thumb CMC joints were followed for 1
      year posttreatment, and matched with four procedure candidates who remained
      untreated. We observed positive outcomes in the treatment group for both symptoms
      and function related to the OA, compared with a reported worsening among the
      untreated controls. While these results should be interpreted with caution
      because of the small number of treated subjects and lack of placebo control and
      randomization, we find sufficient evidence for further investigation of MSC
      therapy as an alternative to more invasive surgery in patients with OA of the
      hand.

PMID- 23949565
TI  - Treatment and prevention of postoperative complications in hip fracture patients:
      infections and delirium.
AB  - The course of older patients with hip fractures is often complicated by
      infections and delirium. Accurate care and high suspicion for these complications
      are essential, since these conditions are associated with an increase in
      mortality, length of hospital stay and nursing home placement, poorer mobility,
      and functional decline. Because of immunosenescence and higher infection rates,
      older patients need specific care, immediate diagnosis, and treatment of
      infections. Numerous guidelines of various medical societies outline the
      management of nosocomial infections, but there is a need of an individualized
      treatment plan because of comorbidities and polypharmacy. Hygiene measures have
      first priority to reduce the rate of infections. Treatment of geriatric syndromes
      like malnutrition, exsiccosis, gait disorders, falls, delirium, urine
      incontinence, and organ insufficiency are as important as immunization against
      pneumococci and influenza. Advanced age, cognitive impairment, hearing loss,
      peripheral vascular disease, prior delirium episodes, sight disorders, and
      polypharmacy are established risk factors for delirium; thus, older people with
      several chronic diseases are prone to delirium. A multifactorial approach,
      comprising standardized screening, oxygen support, intravenous fluid
      administration and augmented nutrition, monitoring of vital signs, pain
      treatment, optimized medication, and modification in perioperative management,
      significantly reduces delirium incidence during hospitalization for hip fracture.
      An interdisciplinary approach between surgeons and geriatricians may warrant
      optimized satisfaction of patients' needs. 

PMID- 23949566
TI  - Tinea atypica: report of nine cases.
AB  - Fungal infections of the skin are a common condition, usually easy to diagnose
      and treat. When the infection is clinically mimicking another cutaneous disorder
      or when the clinical presentation is modified by the use of inappropriate
      treatment, it is referred to as tinea atypica or tinea incognito.We report a
      series of nine cases of patients with tinea atypica, imitating and diagnosed
      initially as different skin diseases. Two patients were defined as pyoderma in
      the facial and pubic regions (caused respectively by Trichophyton mentagrophytes
      var. mentagrophytes and Microsporum canis) and one as herpes zoster ophthalmicus
      (caused by Trichophyton rubrum). Six additional patients were initially
      misdiagnosed: (1) Plaque-like formation of the skin misdiagnosed as an
      impetiginized eczema (with isolated agent Trichophyton verrucosum). (2) A rare
      form of skin infection of the hand caused by T. rubrum, imitating clinically
      cutaneous infection with tuberculum mulgentium. (3) Rosacea-like dermatitis with
      an isolated agent Fusarium. (4) A patient with the typical clinical symptoms of
      seborrheic dermatitis of the face (and with isolated T. rubrum as a causative
      agent). (5) Another patient presented with a widespread folliculitis by
      Trichophyton mentagrophytes. (6) In a patient with bullous pemphigoid and
      immunosuppression pemphigoid-like eruptions were caused by Malassezia
      pachydermatis and T. rubrum. The diagnosis in the presented cases was based on
      direct microscopic examination with KOH and a culture on Sabouraud agar.After the
      diagnosis of tinea, treatment with topical and systemic antifungal agents was
      administrated, followed by complete clinical remissions in all cases.The clinical
      manifestations of tinea atypica can mimic a large number of other dermatoses,
      which often leads to misdiagnosing, and as a consequence--to serious difficulties
      in the management of clinical symptoms and in offering appropriate therapy.

PMID- 23949567
TI  - [In memory of Prof. Dr. Walter H. Horl 11.7.1945 - 25.6.2013].

PMID- 23949568
TI  - Psychopharmacology in psycho-oncology.
AB  - Psychopharmacological intervention is a major clinical and research area in
      oncology and palliative care. Over the last 35 years, psychotropic drugs have
      been shown to have a number of important indications for the treatment of the
      most common psychiatric disorders, such as depression, anxiety, stress-related
      syndromes, severe adjustment disorders, sleep disorders and delirium, which
      combined affect at least 30-40% of patients with cancer and even a higher
      percentage of patients in an advanced phase of illness. The availability of new
      drugs, with less side-effects and safer pharmacological profiles, has been a
      major advance in clinical psycho-oncology. Interestingly, several drugs have also
      been found to be helpful for the adjuvant treatment of cancer-related symptoms,
      such as pain, hot flashes, pruritus, nausea and vomiting, fatigue, and cognitive
      impairment, making psychopharmacology an important tool for the improvement of
      cancer patients' quality of life. The aim of this paper is to summarize recent
      relevant data concerning the use of psychotropic drugs, namely antidepressants,
      anxiolytics, antipsychotics, anticonvulsants and psychostimulants in patients
      with cancer. 

PMID- 23949570
TI  - Iceland-genetic counseling services.
AB  - This brief report aims to give an overview of the history and current status of
      clinical genetics services in Iceland and specific genetic counseling
      considerations for Iceland's population. Presently, there are two part time
      medical geneticists and one full time genetic counselor with an MSc education
      from Cardiff, within the Department of Genetic and Molecular Medicine, based in
      Iceland's only tertiary healthcare facility, Landspitali, the National University
      Hospital. An oncologist (20 %) also contributes to the cancer genetic counseling
      service. In addition, a pediatric medical geneticist has a 25 % appointment at
      the Children's Hospital. No other health care organization offers genetic
      counseling, and there are no private genetic counseling services. 

PMID- 23949569
TI  - Ketamine, sleep, and depression: current status and new questions.
AB  - Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has well-described
      rapid antidepressant effects in clinical studies of individuals with treatment
      resistant major depressive disorder (MDD). Preclinical studies investigating the
      effects of ketamine on brain-derived neurotrophic factor (BDNF) and on sleep slow
      wave activity (SWA) support its use as a prototype for investigating the
      neuroplastic mechanisms presumably involved in the mechanism of rapidly acting
      antidepressants. This review discusses human EEG slow wave sleep parameters and
      plasma BDNF as central and peripheral surrogate markers of plasticity, and their
      use in assessing ketamine's effects. Acutely, ketamine elevates BDNF levels, as
      well as early night SWA and high-amplitude slow waves; each of these measures
      correlates with change in mood in depressed patients who respond to ketamine. The
      slow wave effects are limited to the first night post-infusion, suggesting that
      their increase is part of an early cascade of events triggering improved mood.
      Increased total sleep and decreased waking occur during the first and second
      night post infusion, suggesting that these measures are associated with the
      enduring treatment response observed with ketamine. 

PMID- 23949571
TI  - New insights into 1,2,4-trioxolane stability and the crucial role of ozone in
      promoting polymer degradation.
AB  - Quantum chemical calculations reveal that ozone is capable of instigating a
      series of degradative processes in poly(methyl methacrylate). The crux lies in
      the self-decomposition of 1,2,4-trioxolane, which undergoes a spin intersystem
      crossing process and O-O bond cleavage to unravel a triplet biradical
      intermediate that facilitates auto-degradation of the polymer chain. 

PMID- 23949572
TI  - Factors influencing organizational adoption and implementation of clinical
      genetic services.
AB  - PURPOSE: We sought to identify characteristics of genetic services that
      facilitate or hinder adoption. METHODS: We conducted semi-structured key
      informant interviews in five clinical specialties (primary care, medical
      oncology, neurology, cardiology, pathology/laboratory medicine) within 13
      Veterans Administration facilities. RESULTS: Genetic services (defined as genetic
      testing and consultation) were not typically characterized by informants (n = 64)
      as advantageous for their facilities or their patients; compatible with
      organizational norms of low cost and high clinical impact; or applicable to
      patient populations or norms of clinical care. Furthermore, genetic services had
      not been systematically adopted in most facilities because of their complexity:
      knowledge of and expertise on genetic testing was limited, and organizational
      barriers to utilization of genetic services were formidable. The few facilities
      that had some success with implementation of genetic services had knowledgeable
      clinicians interested in developing services and organizational-level
      facilitators such as accessible genetic test-ordering processes. CONCLUSION:
      Adoption and implementation of genetic services will require a multilevel effort
      that includes education of providers and administrators, opportunities for
      observing the benefits of genetic medicine, strategies for reducing the
      complexity of genomic medicine, expanded strategies for accessing genetics
      expertise and streamlining utilization, and resources dedicated to assessing the
      value of genetic information for the outcomes that matter to health-care
      organizations.

PMID- 23949573
TI  - Storing and interpreting genomic information in widely deployed electronic health
      record systems.
AB  - Electronic health record systems are in widespread use but currently have very
      limited genomic capabilities. Electronic health record systems are a logical
      place for patient genomic information to be stored and used for decision support
      and improvement of patient care. Genomic data and their automated interpretation
      are very challenging for electronic health record software development because
      they are substantially different than other kinds of electronic health record
      data and decision support. Those differences, the resulting challenges, and
      possible solutions are reviewed in this article.

PMID- 23949574
TI  - Reassessing the HPI: the Chronology of Present Illness (CPI).

PMID- 23949575
TI  - Gold-catalyzed cascade cycloisomerization of 1,7-diyn-3,6-bis(propargyl
      carbonate)s: stereoselective synthesis of naphtho[b]cyclobutenes.
AB  - Gold-catalyzed cycloisomerization of 1,7-diyn-3,6-bis(propargyl carbonate)s leads
      to a highly efficient and diastereoselective synthesis of functionalized
      naphtho[b]cyclobutenes. A cascade sequence involving gold-catalyzed double 3,3
      rearrangement, 6pi-electrocyclic reaction and a decarbonylative cyclization was
      proposed for this reaction. 

PMID- 23949576
TI  - Adding pineapple juice to a polyethylene glycol-based bowel cleansing regime
      improved the quality of colon cleaning.
AB  - BACKGROUND/AIMS: An unsuccessful colonoscopy procedure is often related to
      inadequate bowel cleansing. It is difficult for patients to finish the whole 4
      liters of polyethylene glycol-electrolyte lavage (PEG-EL) because of its salty
      taste and the large quantity. Pineapple juice has been shown to be an effective
      agent in the dissolution of undigested food in the stomach. This study assessed
      the effectiveness of both 2 and 4 liters of PEG-EL in precolonoscopic bowel
      cleansing and the quality of colonoscopic cleaning by adding 1 liter of pineapple
      juice to a reduced-volume PEG-based regime. METHODS: The patients were chosen
      from those undergoing a colonoscopic procedure. A total of 126 patients were
      randomized into 3 groups receiving 3 different PEG-EL (Golytely(r)) regimes, i.e.
      4 liters of PEG-EL (group 1, n = 44), 2 liters of PEG-EL (group 2, n = 39) or 2
      liters of PEG-EL with 1 liter of pineapple juice (Dimes(r) 100%; group 3, n =
      43). RESULTS: Both the 4- and 2-liter PEG-EL regimes resulted in similar bowel
      cleansing scores in all parts of the colonic segments. However, adding 1 liter of
      pineapple juice to the reduced-volume PEG-EL regime improved the quality of the
      cleansing on the right side of the colon and in the transverse colon. Adequate
      bowel cleansing was achieved in 68.1% of the patients in group 1, 63.9% in group
      2 and 80% in group 3 (the lowest score in one of the segments). On the other
      hand, the tolerability of the regimes was similar in all 3 groups (p = 0.509).
      CONCLUSIONS: Reduced PEG-EL (2 rather than 4 liters) may be sufficient for
      precolonoscopic bowel cleansing in the Turkish population. Administration of
      pineapple juice in the reduced-dose preparation regime may improve the quality of
      the bowel cleaning.

PMID- 23949577
TI  - The effects of race and other socioeconomic factors on health service use among
      American military veterans.
AB  - This study examined the extent to which racial disparities in service utilization
      exist in veterans (VA) and non-VA health care systems. An observational study
      design was used with a nationally representative sample of veterans. Logistic
      regression models were constructed using sociodemographic characteristics, health
      insurance and benefits, and health status as predictors of health service use in
      both VA and non-VA health care systems. A population weighted sample of 19,270
      veterans from the 2001 National Survey of Veterans was used, which included
      17,004 (88.24%) White, 1,864 (9.15%) African American, 414 (2.15%) Native
      American/Alaskan Native, and 87 (0.45%) Asian American/Pacific Islander veterans.
      Results showed that use of the VA health care system was not associated with
      race, but was associated with VA disability compensation, lack of private health
      insurance, and greater health care need. Contrarily, in non-VA healthcare
      systems, veterans who were racial minorities, less educated, and without private
      health insurance were less likely to use services. Together, these findings
      demonstrate the socioeconomic context in which health disparities exist and
      suggest the influence of health insurance on racial disparities in service
      utilization.

PMID- 23949578
TI  - Albuterol administration is commonly associated with increases in serum lactate
      in patients with asthma treated for acute exacerbation of asthma.
AB  - BACKGROUND: Controversy exists around the incidence and cause of hyperlactatemia
      during asthma exacerbations. We evaluated the incidence, potential causes, and
      adverse events of hyperlactatemia in patients with acute asthma exacerbation.
      METHODS: This study was a subanalysis of subjects receiving placebo from a
      prospective, randomized trial evaluating an IV b -adrenergic agonist in acute
      asthma exacerbation. Plasma albuterol, serum lactate, and bicarbonate
      concentrations were measured at baseline and 1.25 h, and dyspnea score and
      spirometry were measured at baseline and hourly for 3 h. All subjects had a
      therapeutic trial comprising 5 to 15 mg nebulized albuterol, 0.5 to 1 mg
      nebulized ipratropium, and at least 50 mg oral prednisone or its equivalent prior
      to initiation of the study. Following randomization, subjects were treated with
      continued albuterol and IV magnesium at the discretion of their treating
      physician. Subjects were followed to hospital admission or discharge with follow
      up at 24 h and 1 week. RESULTS: One hundred seventy-fi ve subjects were enrolled
      in the parent trial, with 84 in the placebo group. Sixty-fi ve had complete data.
      Mean SD albuterol administration prior to baseline was 12.3 5.3 mg. Mean baseline
      lactate was 18.5 8.4 mg/dL vs 26.5 11.8 mg/dL at 1.25 h ( P , .001). Forty-fi ve
      subjects (69.2%) had hyperlactatemia. Mean baseline bicarbonate level was 22.6
      2.9 mEq/L vs 21.9 4.0 mEq/L at 1.25 h ( P 5 .11). Plasma albuterol concentration
      correlated with lactate concentration ( b 5 0.45, P , .001) and maintained a
      significant association after adjusting for asthma severity ( b 5 0.41, P 5
      .001). Hyperlactatemia did not increase the risk of hospitalization or relapse (
      P 5 .26) or was associated with lower FEV 1 % predicted at 3 h ( P 5 .54).
      CONCLUSIONS: Plasma albuterol was significantly correlated with serum lactate
      concentration after adjusting for asthma severity. Hyperlactatemia was not
      associated with poorer pulmonary function as measured by 3-h FEV 1 % predicted or
      increased hospitalization or relapse at 1 week.

PMID- 23949579
TI  - CISH has no non-redundant functions in glucose homeostasis or beta cell
      proliferation during pregnancy in mice.
AB  - AIMS/HYPOTHESIS: Increased beta cell proliferation during pregnancy is mediated
      by the Janus kinase 2/signal transducer and activator of transcription 5
      (JAK2/STAT5) signalling pathway in response to increased lactogen levels.
      Activation of the pathway leads to transcriptional upregulation of Cish (encoding
      cytokine-inducible SH2 domain-containing protein), a member of the suppressor of
      cytokine signalling (SOCS) family of genes, forming a negative-feedback loop.
      Here, we examined whether conditional gene ablation of Cish in the pancreas
      improves beta cell proliferation and beta cell function during pregnancy in mice.
      METHODS: We derived mice with a novel, conditional loxP allele for Cish. Pancreas
      specific ablation of Cish was achieved by crossing Cish (loxP/loxP) mice with
      Pdx1-Cre (Early) mice. Beta cell proliferation was quantified by BrdU labelling.
      Glucose homeostasis was examined with glucose tolerance tests and determination
      of plasma insulin levels. The expression of other Socs genes and target genes of
      p-STAT5 related to beta cell function and beta cell proliferation was determined
      by quantitative PCR. RESULTS: There was no difference in beta cell proliferation
      or glucose homeostasis between the Cish mutant group and the control group. The p
      STAT5 protein level was the same in Cish mutant and control mice. Socs2 gene
      expression was higher in Cish mutant than control mice at pregnancy day 9.5. The
      expression of other Socs genes was the same between control and mutant mice.
      CONCLUSIONS/INTERPRETATION: Our results show that CISH has no non-redundant
      functions in beta cell proliferation or glucose homeostasis during pregnancy in
      mice. Socs2 might compensate for the loss of Cish during pregnancy.

PMID- 23949580
TI  - Time trends in mortality rates in type 1 diabetes from 2002 to 2011.
AB  - AIMS/HYPOTHESIS: The aim of this study was to estimate absolute and relative
      mortality rates in patients with type 1 diabetes at the Steno Diabetes Centre
      relative to the general Danish background population. METHODS: Patients with type
      1 diabetes (n = 4,821) were followed from 1 January 2002 until 1 January 2011,
      with death from any cause as the main outcome. Poisson regression was used to
      model mortality rates by age, diabetes duration and calendar time, according to
      sex. RESULTS: In the period 2002-2010, a total of 673 deaths (402 men, 271 women)
      occurred in the study population during 33,847 years of follow-up of type 1
      diabetes. The predominant cause of death in patients with type 1 diabetes was
      cardiovascular disease. Mortality rates were highest among those with the lowest
      age at onset, particularly men. The mortality rate in the diabetic population
      decreased over that time period by 6.6% and 4.8% per year in men and women,
      respectively; this was substantially greater than the decrease in mortality rates
      in the background population. The decline in standard mortality rate was 4.3% per
      year in men and 2.6% per year in women. Patients who did not develop nephropathy
      had only slightly elevated mortality rates compared with the background
      population. CONCLUSIONS/INTERPRETATION: Despite advances in care, mortality rates
      in the past decade continue to be greater in patients with type 1 diabetes than
      in those without diabetes; however, the mortality rate in patients decreased over
      the study period faster than that of the background population. Nephropathy seems
      to be the main driver of the excess mortality.

PMID- 23949581
TI  - In vitro immunization of Epstein-Barr virus-immortalized B cells augments antigen
      specific antibody production.
AB  - The current method for in vitro immunization (IVI) uses several antigens
      including toxins, food allergens, pathogenic bacteria, and self-antigen-derived
      peptides that induce an antigen-specific immune response in peripheral blood
      mononuclear cells (PBMCs). This protocol, however, requires donor blood
      collection and preparation of PBMCs before every IVI. In the present study, we
      aimed to design a more efficient system utilizing B cells immortalized with
      Epstein-Barr virus (EBV-B) as host cells for IVI to make antigen-specific
      antibodies. Results showed that previously antigen-sensitized, EBV-B cells
      exposed to the antigen along with IL-6, CpG oligonucleotides, and CD40 ligand
      signal produced antigen-specific antibodies. These results provide evidence for a
      novel and easy method to expand memory-type B cells and produce antigen-specific
      antibodies. 

PMID- 23949582
TI  - The cytogenetic action of ifosfamide, mesna, and their combination on peripheral
      rabbit lymphocytes: an in vivo/in vitro cytogenetic study.
AB  - Ifosfamide (IFO) is an alkylating nitrogen mustard, administrated as an
      antineoplasmic agent. It is characterized by its intense urotoxic action, leading
      to hemorrhagic cystitis. This side effect of IFO raises the requirement for the
      co-administration with sodium 2-sulfanylethanesulfonate (Mesna) aiming to avoid
      or minimize this effect. IFO and Mesna were administrated separately on rabbit's
      lymphocytes in vivo, which were later developed in vitro. Cytogenetic markers for
      sister chromatid exchanges (SCEs), proliferation rate index (PRI) and Mitotic
      Index were recorded. Mesna's action, in conjunction with IFO reduces the
      frequency of SCEs, in comparison with the SCEs recordings obtained when IFO is
      administered alone. In addition to this, when high concentrations of Mesna were
      administered alone significant reductions of the PRI were noted, than with IFO
      acting at the same concentration on the lymphocytes. Mesna significantly reduces
      IFO's genotoxicity, while when administered in high concentrations it acts in an
      inhibitory fashion on the cytostatic action of the drug. 

PMID- 23949583
TI  - Effect of iron overload on the pituitary gland and associated imaging findings.

PMID- 23949584
TI  - Challenges in congenital syphilis surveillance: how are congenital syphilis
      investigations classified?
AB  - BACKGROUND: Congenital syphilis is a serious, preventable, and nationally
      notifiable disease. Despite the existence of a surveillance case definition,
      congenital syphilis is sometimes classified differently using an algorithm on the
      Centers for Disease Control and Prevention's case reporting form. METHODS: We
      reviewed Louisiana's congenital syphilis electronic reporting system for
      investigations of infants born from January 2010 to October 2011, abstracted data
      required for classification, and applied the surveillance definition and the
      algorithm. We calculated the sensitivities and specificities of the algorithm and
      Louisiana's classification using the surveillance definition as the surveillance
      gold standard. RESULTS: Among 349 congenital syphilis investigations, the
      surveillance definition identified 62 cases. The algorithm had a sensitivity of
      91.9% and a specificity of 64.1%. Louisiana's classification had a sensitivity of
      50% and a specificity of 91.3% compared with the surveillance definition.
      CONCLUSIONS: The differences between the algorithm and the surveillance
      definition led to misclassification of congenital syphilis cases. The algorithm
      should match the surveillance definition. Other state and local health
      departments should assure that their reported cases meet the surveillance
      definition.

PMID- 23949585
TI  - HIV voluntary counseling and testing of couples during maternal labor and
      delivery: the TRIPAI Couples study.
AB  - BACKGROUND: Women in Brazil are routinely tested for HIV-1 during pregnancy with
      rapid testing repeated during labor in some settings. Partner testing is not
      routinely offered. The peripartum period provides opportunity for HIV testing of
      couples. METHODS: A cross-sectional study was conducted in a large public
      hospital in southern Brazil. HIV rapid testing was offered to all pregnant women
      in labor. Male partners of women who consented to partner inclusion were offered
      testing. Within HIV-serodiscordant couples, HIV-negative individuals were
      evaluated for the delta-32 base-pair CCR5 deletion allele. RESULTS: From February
      to September 2009, 2888 women delivered, with 1729 eligible women approached for
      study participation; 1648 (95%) HIV-negative women consented to partner testing
      and 66% of partners accepted testing. Seven HIV-infected men (0.6%) with no prior
      diagnosis were identified. Testing strategies uncovered 7 additional
      serodiscordant couples, 4 HIV-infected women diagnosed at delivery, and 3 HIV
      infected men who had not disclosed their status to their partners, for a total
      serodiscordance rate of 1.3% in 1101 couples. No cases of acute maternal or
      infant infection were noted. No delta-32 base-pair deletions were identified in
      14 HIV-negative partners in serodiscordant relationships. Parameters associated
      with increased acceptance of partner testing included higher income (P = 0.003),
      education (P < 0.0001), stable relationships of longer duration (P = 0.001), and
      female support of partner testing (P < 0.0001). CONCLUSIONS: Testing of couples
      at the time of labor and delivery is a feasible public health strategy in areas
      of moderate-to-high HIV prevalence, which can potentially prevent acute
      infections in men, women, and infants.

PMID- 23949586
TI  - Intravaginal metronidazole/miconazole for the treatment of vaginal
      trichomoniasis.
AB  - BACKGROUND: Trichomonas vaginalis is the causative agent of the most common
      curable sexually transmitted disease in the world. The infection is treated with
      a single oral dose of metronidazole or tinidazole, currently the only licensed
      class of drugs available for this indication; however, both of these
      antimicrobials are associated with significant gastrointestinal adverse effects,
      and some individuals are unable to tolerate them because of these adverse
      effects. METHODS: Randomized, dose-ranging pilot study conducted in 2 phases
      consisting of 20 participants in each phase. In the first phase, participants
      were randomized to the vaginal suppository (metronidazole 750 mg/miconazole
      nitrate 200 mg) twice a day for 7 days versus oral metronidazole 2 g single dose.
      In the second phase, participants randomized to suppository used it once a day
      for 7 days. Women were reevaluated on days 12 to 15 and 30 to 35. Treatment
      failures were defined as persistence of trichomonas by wet prep and/or culture.
      RESULTS: There were no significant differences in cure rates between the vaginal
      suppositories and oral metronidazole in either phase. The overall efficacy across
      both follow-up visits was 80% versus 90% for the suppository (2*/d) versus oral
      medication arms in phase 1 (P = 1.00) and 78% versus 70% for the suppository
      (1*/d) versus oral medication arms in phase 2 (P = 1.00). The results were also
      nonsignificant when combining results across arm (P = 1.00). CONCLUSIONS: High
      dose intravaginal metronidazole combined with miconazole offers the possibility
      of a well-tolerated treatment that avoids the systemic adverse effects of
      nitroimidazoles for the treatment of trichomoniasis.

PMID- 23949587
TI  - Incident anal human papillomavirus and human papillomavirus-related sequelae in
      HIV-infected versus HIV-uninfected adolescents in the United States.
AB  - BACKGROUND: Little is known about the incidence of anal human papillomavirus
      (HPV) infection and related sequelae, as well as factors associated with these
      outcomes, among adolescents who are HIV infected versus HIV uninfected but at
      risk. METHODS: We analyzed the data from a multisite US study, the Reaching for
      Excellence in Adolescent Care and Health Project. Adolescents aged 12 to 18 years
      who were behaviorally HIV infected (n = 319) or HIV uninfected but at risk (n =
      177) were recruited. Incidence rates for anal HPV, high-risk anal HPV, anogenital
      warts, and anal dysplasia were calculated using Poisson modeling. Factors
      associated with these outcomes were examined using Cox proportional hazards
      modeling. RESULTS: Mean age at entry was 16.8 years; mean (SD) follow-up time for
      detection of anal HPV was 22.4 (10.8) months. Most participants (76%) were
      female; 70% were black non-Hispanic. HIV-infected (vs. HIV-uninfected) women had
      a significantly higher incidence of anal HPV (30 vs. 14 per 100 person-years; P =
      0.002), high-risk anal HPV (12 vs. 5.3 per 100 person-years; P = 0.04), and
      anogenital warts (6.7 vs. 1.6 per 100 person-years; P = 0.002) but not anal
      dysplasia. Although incidence rates were higher for these outcomes among HIV
      infected versus HIV-uninfected men, the differences were not statistically
      significant. Among women, factors associated with anal HPV and related sequelae
      differed by HIV status and included biological, behavioral, and HIV-related
      factors. No factors were associated with outcomes in men. CONCLUSIONS: HIV
      infected versus HIV-uninfected adolescent women had higher rates of anal HPV and
      anogenital warts. Because HIV-infected youth are at increased risk of these
      outcomes, enhanced HPV prevention efforts such as vaccination are warranted for
      this group.

PMID- 23949588
TI  - Why do men who have sex with men test for HIV infection? Results from a community
      based testing program in Seattle.
AB  - BACKGROUND: The Centers for Disease Control and Prevention recommends at least
      annual HIV testing for men who have sex with men (MSM), but motivations for
      testing are not well understood. METHODS: We evaluated data from MSM testing for
      HIV at a community-based program in King County, Washington. Correlates of
      regular testing were examined using generalized estimating equation regression
      models. RESULTS: Between February 2004 and June 2011, 7176 MSM attended 12,109
      HIV testing visits. When asked reasons for testing, 49% reported that it was time
      for their regular test, 27% reported unprotected sex, 24% were starting
      relationships, 21% reported sex with someone new, 21% sought sexually transmitted
      infection/hepatitis screening, 12% reported sex with an HIV-infected partner, 2%
      suspected primary HIV infection, and 16% reported other reasons. In multivariable
      analysis, factors associated with regular testing included having a regular
      health care provider and the following in the previous year: having only male
      partners, having 10 or more male partners, inhaled nitrite use, not injecting
      drugs, and not having unprotected anal intercourse with a partner of
      unknown/discordant status (P <= 0.001 for all). Men reporting regular testing
      reported shorter intertest intervals than men who did not (median of 233 vs. 322
      days, respectively; P < 0.001). CONCLUSIONS: Regular testing, sexual risk, and
      new partnerships were important drivers of HIV testing among MSM, and regular
      testing was associated with increased testing frequency. Promoting regular
      testing may reduce the time that HIV-infected MSM are unaware of their status,
      particularly among those who have sex with men and women or inject drugs.

PMID- 23949589
TI  - Risk factors for high-risk human papillomavirus detection among HIV-negative and
      HIV-positive women from Tanzania.
AB  - BACKGROUND: Human papillomavirus (HPV) is one of the most common sexually
      transmitted infections worldwide. The prevalence is dependent on several known
      factors notably sexual behavior and age, and factors still under scrutiny.
      OBJECTIVE: This study aimed to examine risk factors for high-risk (HR) HPV
      infection among HIV-positive and HIV-negative women from the general population
      of Tanzania and to assess whether specific risk factors could contribute to the
      high prevalence of HR HPV infection in older age found in some populations
      including Tanzanian women. METHODS: A cross-sectional study of 3699 women from
      Tanzania was conducted. We obtained information on sociodemographic and lifestyle
      factors through personal interview. Cervical swabs were collected for detection
      of HR HPV (Hybrid Capture 2; Qiagen, Hildesheim, Germany) and genotyping
      (LiPaExtra; Innogenetics, Gent, Belgium). Finally, we obtained a blood sample for
      HIV testing. RESULTS: HIV positivity was the strongest risk factor for HR HPV
      (odds ratio, 4.1; 95% confidence interval, 3.3-5.3). Young age, shorter duration
      of present relationship, and increasing number of sex partners were also
      associated with higher risk for HR HPV. Among women 20 to 29 years old,
      especially number of partners (P = 0.005) and HIV positivity (P < 0.0001)
      determined the risk. In underweight women 50 years or older (P = 0.004) and HIV
      positivity (P = 0.0009) increased the risk, whereas increasing number of partners
      was not related to the risk of HR HPV (P = 0.46). CONCLUSIONS: Human
      papillomavirus risk factors among HIV-positive and HIV-negative women were
      similar, but the strength of association was greater among HIV-positive women,
      notably for lifetime number of sex partners, time in present relationship,
      genital warts, and body mass index. We were not able to identify a clear
      explanation for the high HPV prevalence among older women. However, in the age
      stratified analysis, potential indicators of decreased immunity increased the
      risk for HPV infection among older women, whereas in younger women, risk was
      particularly associated with sexual activity.

PMID- 23949590
TI  - Bacterial vaginosis among African American women who have sex with women.
AB  - BACKGROUND: Bacterial vaginosis (BV) is a frequent cause of vaginal discharge
      that may be more common among women reporting sex with women (WSW). The objective
      of this study was to determine the prevalence of BV and predictors of infection
      among a sample of African American WSW. METHODS: African American WSW aged 18
      years or older presenting to the Mississippi State Department of Health STD
      Clinic between 2009 and 2010 and reporting a history of sexual activity with a
      female partner during the preceding year were invited to participate. A survey on
      sexual history and sexual behavior characteristics was completed. Bacterial
      vaginosis was defined by Amsel criteria. Associations with participant
      characteristics were determined using logistic regression analysis. RESULTS:
      Bacterial vaginosis was diagnosed in 93 (47.4%) of 196 women. Bisexual identity
      (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.03-3.66; P = 0.04),
      douching within the past 30 days (OR, 1.93; 95% CI, 1.09-3.43; P = 0.02), age 18
      years or less at first sexual encounter with a female partner (OR, 3.18; 95% CI,
      1.16-8.71; P = 0.02), and report of more than 1 lifetime male sexual partners
      (OR, 1.94; 95% CI, 1.01-3.74; P = 0.04) were significant predictors of BV in
      bivariate analysis. Bacterial vaginosis was less common among women who reported
      more than 1 lifetime female sexual partner (OR, 0.26; 95% CI, 0.09-0.76; P =
      0.01). In multivariable analysis, age 18 years or less at first sex with a female
      partner approached significance, while report of 1 lifetime female sexual partner
      remained strongly associated with BV. CONCLUSIONS: Bacterial vaginosis was common
      in this sample of African American WSW and significantly associated with report
      of 1 lifetime female sexual partner.

PMID- 23949591
TI  - Gonococcal susceptibility to cephalosporins--Hawaii, 2003 to 2011.
AB  - Among gonococcal isolates examined at the Hawaii State Laboratory Division from
      2003 to 2011, the prevalence of elevated cefixime minimum inhibitory
      concentrations (MICs; >=0.064 MUg/mL) and elevated cefpodoxime MICs (>=0.19
      MUg/mL) increased over time. In contrast, few isolates exhibited elevated
      ceftriaxone MICs (>=0.094 MUg/mL), and the prevalence of elevated ceftriaxone
      MICs did not change. 

PMID- 23949592
TI  - Urinary low-molecular-weight protein excretion in pediatric idiopathic nephrotic
      syndrome.
AB  - BACKGROUND: Minimal change disease (MCD) and focal segmental glomerulosclerosis
      (FSGS) are the most common causes of idiopathic nephrotic syndrome (INS). We have
      evaluated the reliability of urinary neutrophil-gelatinase-associated lipocalin
      (uNGAL), urinary alpha1-microglobulin (ualpha1M) and urinary N-acetyl-beta-D
      glucosaminidase (ubetaNAG) as markers for differentiating MCD from FSGS. We have
      also evaluated whether these proteins are associated to INS relapses or to
      glomerular filtration rate (GFR). METHODS: The patient cohort comprised 35
      children with MCD and nine with FSGS; 19 healthy age-matched children were
      included in the study as controls. Of the 35 patients, 28 were in remission (21
      MCD, 7 FSGS) and 16 were in relapse (14 MCD, 2 FSGS). The prognostic accuracies
      of these proteins were assessed by receiver operating characteristic (ROC) curve
      analyses. RESULTS: The level of uNGAL, indexed or not to urinary creatinine
      (uCreat), was significantly different between children with INS and healthy
      children (p = 0.02), between healthy children and those with FSGS (p = 0.007) and
      between children with MCD and those with FSGS (p = 0.01). It was not
      significantly correlated to proteinuria or GFR levels. The ROC curve analysis
      showed that a cut-off value of 17 ng/mg for the uNGAL/uCreat ratio could be used
      to distinguish MCD from FSGS with a sensitivity of 0.77 and specificity of 0.78.
      ubetaNAG was not significantly different in patients with MCD and those with FSGS
      (p = 0.86). Only ualpha1M, indexed or not to uCreat, was significantly (p <
      0.001) higher for patients in relapse compared to those in remission.
      CONCLUSIONS: Our results indicate that in our patient cohort uNGAL was a reliable
      biomarker for differentiating MCD from FSGS independently of proteinuria or GFR
      levels.

PMID- 23949593
TI  - Association between childhood nephrotic syndrome and hemophagocytic
      lymphohistiocytosis.
AB  - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is caused by an excessive
      activation of nonmalignant macrophages. Renal lesions have been described in
      association with, but always after, HLH diagnosis. CASE-DIAGNOSIS: We describe a
      previously healthy 26-month-old girl who presented originally with steroid
      responsive nephrotic syndrome (NS), but after 4 months, on the first NS relapse,
      experienced numerous complications (many of them reported to accompany NS as
      single events). Clinical and laboratory signs of HLH evolved with time and led to
      deterioration of her condition and death, within 5 months of her original
      presentation. CONCLUSIONS: To our knowledge, this is the first report of NS
      antedating the presentation of HLH.

PMID- 23949594
TI  - Congenital nephrotic syndrome with prolonged renal survival without renal
      replacement therapy.
AB  - BACKGROUND: Infants with congenital nephrotic syndrome (CNS) develop severe
      nephrotic syndrome that is resistant to medical therapy, and bilateral
      nephrectomy is recommended toward the end of the first year of life followed by
      renal replacement therapy. CNS infants in New Zealand have been observed to
      exhibit a different course to those with the typical Finnish mutation. METHODS: A
      database of CNS children at our center was retrospectively examined. All cases
      diagnosed between 1975 and 2011 were reviewed. Demographic data, clinical
      features, genetic mutations, treatment, and outcome were extracted from clinical
      records. RESULTS: Thirty-five patients with CNS, 23 children of Maori descent,
      and 12 Caucasians . Fourteen had died of either bacterial sepsis or intracranial
      thrombosis. Maori children had displayed a highly variable and protracted
      timeline to end-stage renal disease (ESRD) with median renal survival of 30 years
      versus 0.7 years in Caucasian patients. Mutation analysis of NPHS1 showed a
      founder mutation in the Maori population. CONCLUSIONS: Congenital nephrotic
      syndrome in New Zealand Maori children exhibit a different clinical course to
      Caucasian children and have a mutation that was first described in this ethnic
      group.

PMID- 23949596
TI  - A case of spontaneous extracranial epidural emphysema.
AB  - OBJECTIVE: To report a rare case of spontaneous extracranial epidural emphysema.
      CLINICAL PRESENTATION AND INTERVENTION: An 18-year-old woman with a recent
      diagnosis of squamous cell carcinoma of the esophagus presented with acute onset
      of cough, dyspnea and subcutaneous emphysema. An esophageal endoscopy revealed an
      ulcerative lesion in the upper third of the esophagus that was diagnosed as
      squamous cell carcinoma. A computed tomographic scan of the chest showed spinal
      epidural emphysema in addition to pneumomediastinum and pneumoperitoneum. A few
      days later, the patient died of aspiration pneumonia and persistent epidural
      emphysema. CONCLUSION: The spontaneous extracranial epidural emphysema in our
      case resulted from a bout of cough with tracking of air from the
      pneumomediastinum through the emaciated tissue planes into the epidural space.

PMID- 23949595
TI  - Antagonistic and stimulative roles of ADAR1 in RNA silencing.
AB  - Adenosine deaminases acting on RNA (ADARs) are involved in RNA editing that
      converts adenosine residues to inosine specifically in double-stranded RNAs
      (dsRNA). This A-to-I RNA editing pathway and the RNA interference (RNAi) pathway
      seem to interact antagonistically by competing for their common dsRNA substrates.
      For instance, A-to-I editing of certain microRNA (miRNA) precursors by ADAR1 and
      ADAR2 inhibits their processing to mature miRNAs. Recent studies unexpectedly
      revealed the presence of a completely different type of interaction between the
      RNA editing mechanism and the RNAi machinery. ADAR1 forms a complex via direct
      protein-protein interaction with Dicer, an RNase III gene family member involved
      in the RNAi mechanism. ADAR1 in the Dicer complex promotes pre-miRNA cleavage by
      Dicer and facilitates loading of miRNA onto RNA-induced silencing complexes,
      giving rise to an unsuspected stimulative function of ADAR1 on miRNA processing
      and RNAi mechanisms. ADAR1 differentiates its functions in RNA editing and RNAi
      by formation of either ADAR1-ADAR1 homodimer or Dicer-ADAR1 heterodimer
      complexes. Expression of miRNAs is globally inhibited in ADAR1-null mouse
      embryos, which, in turn, alters expression of their target genes and may
      contribute to their embryonic lethal phenotype. 

PMID- 23949600
TI  - Host response: LPS goes non-canonical.

PMID- 23949601
TI  - Back to the future!

PMID- 23949604
TI  - Inorganic arsenic in the Japanese diet: daily intake and source.
AB  - The concentrations of arsenic (As) species in 19 food composites prepared from
      159 food items purchased in Shizuoka city, Japan, were determined (1) to estimate
      total daily intake of inorganic As (InAs) and some organic As species and (2) to
      determine food contributing to total daily InAs intake. As analysis included
      extraction of As species with a synthetic gastric juice (0.07 mol/L HCl + 0.01 %
      pepsin) from food composite and high-performance liquid chromatography-high
      efficiency photo-oxidation-hydride generation-inductively coupled plasma mass
      spectrometry. InAs was detected in 9 of 19 food composites at a concentration of
      0.423-450 ng As/g fresh-weight. Daily intake of InAs from cereals was greatest
      (13 MUg/person/day) followed by algae (5.7 MUg/person/day), and the intake from
      the two categories constituted 90 % of the total daily InAs intake of adults (21
      MUg/person/day on a bioaccessible-fraction basis and 24 MUg/person/day on a
      content basis). Analysis of individual food items showed that rice and hijiki
      contributed virtually 100 % of InAs from cereals and algae, respectively. The
      present survey indicated that InAs from rice and hijiki consumption contributed
      to total daily InAs intake and consequently to significant cancer risk of the
      general Japanese population. Daily intake of some organic forms of As and their
      contributing food categories was also estimated. 

PMID- 23949603
TI  - How carbohydrates sculpt cells: chemical control of morphogenesis in the yeast
      cell wall.
AB  - In budding yeast, the neck that connects the mother and daughter cell is the site
      of essential functions such as organelle trafficking, septum formation and
      cytokinesis. Therefore, the morphology of this region, which depends on the
      surrounding cell wall, must be maintained throughout the cell cycle. Growth at
      the neck is prevented, redundantly, by a septin ring inside the cell membrane and
      a chitin ring in the cell wall. Here, we describe recent work supporting the
      hypothesis that attachment of the chitin ring, which forms at the mother-bud neck
      during budding, to beta-1,3-glucan in the cell wall is necessary to stop growth
      at the neck. Thus, in this scenario, chemistry controls morphogenesis.

PMID- 23949602
TI  - How to get (a)round: mechanisms controlling growth and division of coccoid
      bacteria.
AB  - Bacteria come in a range of shapes, including round, rod-shaped, curved and
      spiral cells. This morphological diversity implies that different mechanisms
      exist to guide proper cell growth, division and chromosome segregation. Although
      the majority of studies on cell division have focused on rod-shaped cells, the
      development of new genetic and cell biology tools has provided mechanistic
      insight into the cell cycles of bacteria with different shapes, allowing us to
      appreciate the underlying molecular basis for their morphological diversity. In
      this Review, we discuss recent progress that has advanced our knowledge of the
      complex mechanisms for chromosome segregation and cell division in bacteria which
      have, deceptively, the simplest possible shape: the cocci. 

PMID- 23949605
TI  - [Cystic tumor on the porta hepatis].
AB  - A cystic entity from the porta hepatis of a 64-year-old female patient was sent
      in for rapid section diagnostics with a clinical suspicion of pancreatic cancer.
      The rapid section diagnostics revealed aspects of glandular proliferation with
      mucous-like material in the lumina which led to the suspicion of infiltration of
      a highly differentiated mucinous adenocarcinoma. However, conventional paraffin
      section histology and the immunohistochemical marker profile could not confirm
      this suspicion but an adenomatoid tumor was diagnosed. In typical locations in
      the genital area of both genders, this entity is a current differential diagnosis
      to infiltrations of an adenocarcinoma. 

PMID- 23949606
TI  - Flat panel detector computed tomography for the interaction between contrast
      enhanced thrombi and stent retrievers in stroke therapy: a pilot study.
AB  - OBJECTIVES: The purpose of this study was to create virtual 3D views of the
      interaction between contrast-enhanced thrombi and three different types of stent
      retrievers. MATERIALS AND METHODS: Artificial thrombi with and without contrast
      agent were created and introduced into a silicone tube with saline solution. The
      stent retrievers (Aperio (A), Solitaire FR (B), Revive (C)) were released around
      the thrombi. For each retriever, two sets (0 min, 5 min) of flat panel computed
      tomography (CT) data were acquired on a Siemens Axiom Artis Zee biplane
      angiography system and reconstructed using syngo InSpace 3D software. RESULTS:
      The filaments of all three stent retrievers were displaced by the thrombus
      immediately after deployment. Another study series after 5 min showed further
      expansion of the stents into the thrombus. A tends to appose best around
      obstacles. A and B allow cushion-like bulging of clot material into the stent
      lumen. C showed only moderate curvilinear bulging and a minor degree of
      interaction in between stent filaments and thrombus. CONCLUSIONS: Flexible design
      allows better apposition of the device to the surface of the thrombus. A
      relatively strong longitudinal structure combined with large gaps in between the
      stent filaments seems to favor migration into the clot. The main capture
      mechanism seems to be engagement of the clot between the crossings of stent
      struts.

PMID- 23949607
TI  - Brachial amyotrophic diplegia associated with the a140a superoxide dismutase 1
      mutation.

PMID- 23949608
TI  - Beta amyloid peptide (25-35) leading to inflammation through Toll-like receptors
      and the anti-inflammatory effect of genistein in BV-2 cells.
AB  - Genistein, the main soy isoflavone component, has received much attention for its
      potential multifunction. Here, we reported that in BV-2 cells, genistein
      significantly inhibited beta amyloid peptides 25-35 (Abeta25-35)-induced
      inflammatory response. The results indicated that Abeta25-35-stimulated BV-2
      cells upregulated Toll-like receptors 2 and 4, Myd88, and IKK gene expression
      with the increasing expression of IL-6 and decreasing expression of TGF-beta and
      IL-10. Further, inhibiting TLR4 expression with small interfering RNA prevented
      the inflammatory response induced by Abeta25-35, indicating the key role of TLRs
      in Abeta-mediated inflammation. Genistein pre-treated BV-2 cells showed less
      inflammatory response when exposed to Abeta25-35. These results suggested that
      Abeta induced BV-2 cells inflammation though TLRs and genistein has an anti
      inflammatory effect in vitro. 

PMID- 23949610
TI  - Abstracts of the 49th EASD (European Association for the Study of Diabetes)
      Annual Meeting. September 23-27, 2013. Barcelona, Spain.

PMID- 23949609
TI  - Dual contradictory effect of H-89 on neuronal retraction, death and inflammation
      in differentiated PC12 cells subjected to oxidative stress.
AB  - Interrelation between oxidative stress and neuro-inflammation has been discussed
      extensively to contribute to neuronal dysfunction in neurodegenerative disorders.
      In this manner, it seems that there is an intriguing link between protein kinase
      A (PKA), neuronal apoptosis and inflammation. Rat PC12 pheochromocytoma cell can
      be induced to differentiate into neuron-like cells possessing elongated neurites
      by nerve growth factor. In this study, we investigated the effect of H-89, a
      selective inhibitor of PKA, on the neurite retraction along with evaluation of
      cell death and inflammatory markers in the differentiated PC12 cells, exposed to
      H2O2. We found that dose-dependent inhibition of PKA by low and medium
      concentrations of H-89 (5, 7 and 10 MUM) enhanced the parameters of neurite
      outgrowth and complexity in the cells co-treated with H2O2 as an oxidative
      stress. Similar concentrations of H-89 significantly inhibited cell death and
      neurite retraction induced by oxidative stress. Components of TNF-alpha-NFkappaB
      COX-2 axis, a discussed pathway in neuroinflammation, downregulated dose
      dependently by administration of H-89 in H2O2-induced PC12 cells. In this
      condition, PKA inhibition by the high concentrations of H-89 (15 and 20 MUM) led
      to enhanced cell death and inflammation with decreased neurite outgrowth. These
      findings indicate that H-89 has a dual contradictory effect on oxidative stress
      and inflammation that affect neurite outgrowth and complexity in differentiated
      PC12 cells.

PMID- 23949611
TI  - Specific RNA-protein interactions detected with saturation transfer difference
      NMR.
AB  - RNA, at the forefront of biochemical research due to its central role in biology,
      is recognized by proteins through various mechanisms. Analysis of the RNA-protein
      interface provides insight into the recognition determinants and function. As
      such, there is a demand for developing new methods to characterize RNA-protein
      interactions. Saturation transfer difference (STD) NMR can identify binding
      ligands for proteins in a rather short period of time, with data acquisitions of
      just a few hours. Two RNA-protein systems involved in RNA modification were
      studied using STD NMR. The N (6)-threonylcarbamoyltransferase, YrdC, with
      nucleoside-specific recognition, was shown to bind the anticodon stem-loop of
      tRNA(Lys)UUU. The points of contact on the RNA were assigned and a binding
      interface was identified. STD NMR was also applied to the interaction of the
      archaeal ribosomal protein, L7Ae, with the box C/D K-turn RNA. The
      distinctiveness of the two RNA-protein interfaces was evident. Both RNAs
      exhibited strong STD signals indicative of direct contact with the respective
      protein, but reflected the nature of recognition. Characterization of nucleic
      acid recognition determinants traditionally involves cost and time prohibitive
      methods. This approach offers significant insight into interaction interfaces
      fairly rapidly, and complements existing structural methods. 

PMID- 23949612
TI  - A qualitative inquiry of the financial concerns of couples opting to use
      preimplantation genetic diagnosis to prevent the transmission of known genetic
      disorders.
AB  - Preimplantation genetic diagnosis (PGD) is an innovative prenatal testing option
      because the determination of whether a genetic disorder or chromosomal
      abnormality is evident occurs prior to pregnancy. However, PGD is not covered
      financially under the majority of private and public health insurance
      institutions in the United States, leaving couples to decide whether PGD is
      financially feasible. The aim of this qualitative study was to understand the
      role of finances in the decision-making process among couples who were actively
      considering PGD. In-depth, semi-structured interviews were completed with 18
      genetic high-risk couples (36 individual partners). Grounded theory guided the
      analysis, whereby three themes emerged: 1) Cost is salient, 2) Emotions
      surrounding affordability, and 3) Financial burden and sacrifice. Ultimately,
      couples determined that the opportunity to avoid passing on a genetic disorder to
      a future child was paramount to the cost of PGD, but expressed financial concerns
      and recognized financial access as a major barrier to PGD utilization. 

PMID- 23949613
TI  - Is he a healthy weight? Exposure to obesity changes perception of the weight
      status of others.
AB  - BACKGROUND: The prevalence of obesity has increased dramatically in recent years.
      As exposure to obesity increases, perceptions of what is a 'normal' weight are
      likely to change and this may result in overweight and obese people being
      perceived as healthier weights than they actually are. We tested whether exposure
      to obesity results in individuals being more likely to perceive an overweight
      person as being of healthy weight and whether this would impact upon evaluations
      of whether an overweight person should consider losing weight. METHODS: Across
      three experiments with over 350 participants, we examined the effect that
      exposing participants to photographs of either obese or healthy weight young
      males had on visual judgements of whether an overweight young male was of healthy
      weight. We also tested whether exposure influenced participants' perceptions of
      what a 'normal' weight is, as we predicted that this might mediate the effect
      that obesity exposure has on weight perceptions. RESULTS: In all studies,
      exposure to obesity resulted in an overweight male being perceived to be of
      healthier weight. There was also evidence that this effect was explained by
      changes to perceptions of what is a 'normal' weight (Experiment 2). Obesity
      exposure also resulted in participants being more likely to believe that an
      overweight person did not need to consider losing weight (Experiment 3).
      CONCLUSIONS: These findings provide causal evidence that perceptions of weight
      and health status are strongly influenced by the body weight of the people we see
      around us.

PMID- 23949614
TI  - Commonality versus specificity among adiposity traits in normal-weight and
      moderately overweight adults.
AB  - BACKGROUND: Many adiposity traits have been related to health complications and
      premature death. These adiposity traits are intercorrelated but their underlying
      structure has not been extensively investigated. We report on the degree of
      commonality and specificity among multiple adiposity traits in normal-weight and
      moderately overweight adult males and females (mean body mass index (BMI)=22.9 kg
      m(-2), s.d.=2.4). METHODS: A total of 75 healthy participants were assessed for a
      panel of adiposity traits including leg, arm, trunk, total fat masses and
      visceral adipose tissue (VAT) derived from dual energy X-ray absorptiometry
      (DXA), hepatic and muscle lipids from proton magnetic resonance spectroscopy, fat
      cell volume from an abdominal subcutaneous adipose tissue biopsy (n=36) and
      conventional anthropometry (BMI and waist girth). Spearman's correlations were
      calculated and were subjected to factor analysis. RESULTS: Arm, leg, trunk and
      total fat masses correlated positively (r=0.78-0.95) with each other. VAT
      correlated weakly with fat mass indicators (r=0.24-0.31). Intrahepatic lipids
      (IHL) correlated weakly with all fat mass traits (r=0.09-0.34), whereas
      correlations between DXA depots and intramyocellular lipids (IMCL) were
      inconsequential. The four DXA fat mass measures, VAT, IHL and IMCL depots
      segregated as four independent factors that accounted for 96% of the overall
      adiposity variance. BMI and waist girth were moderately correlated with the arm,
      leg, trunk and total fat and weakly with VAT, IHL and IMCL. CONCLUSION: Adiposity
      traits share a substantial degree of commonality, but there is considerable
      specificity across the adiposity variance space. For instance, VAT, IHL and IMCL
      are typically poorly correlated with each other and are poorly to weakly
      associated with the other adiposity traits. The same is true for BMI and waist
      girth, commonly used anthropometric indicators of adiposity. These results do not
      support the view that it will be possible to identify adequate anthropometric
      indicators of visceral, hepatic and muscle lipid content in normal-weight and
      moderately overweight individuals.

PMID- 23949615
TI  - Gene expression profiling in subcutaneous, visceral and epigastric adipose
      tissues of patients with extreme obesity.
AB  - OBJECTIVE: The goal of the present study was to identify differences in gene
      expression between SAT, VAT and EAT depots in Class III severely obese
      individuals. DESIGN: Human subcutaneous (SAT) and visceral (VAT) adipose tissues
      exhibit differential gene expression profiles. There is little information,
      however, about the other proximal white adipose tissue, epigastric (EAT), in
      terms of its function and contribution to metabolism. SUBJECTS AND METHODS: Using
      RNA from adipose biospecimens obtained from Class III severely obese patients
      undergoing open Roux-en-Y gastric bypass surgery, we compared gene expression
      profiles between SAT, VAT and EAT, using microarrays validated by real-time
      quantitative PCR. RESULTS: The three depots were found to share 1907 genes. VAT
      had the greatest number of genes (66) expressed exclusively in this depot,
      followed by SAT (23), and then EAT (14). Moreover, VAT shared more genes with EAT
      (65) than with SAT (38). Further analyses using ratios of SAT/EAT, VAT/EAT and
      SAT/VAT identified specific as well as overlapping networks and pathways of genes
      representing dermatological diseases, inflammation, cell cycle and growth, cancer
      and development. Targeted analysis of genes, having a role in adipose tissue
      development and function, revealed that Peroxisome proliferator-activated
      receptor Gamma Coactivator 1-alpha (PGC1-alpha) that regulates the precursor of
      the hormone Irisin (FNCD5) were abundantly expressed in all three fat depots,
      along with fibroblast growth factors (FGF) FGF1, FGF7 and FGF10, whereas, FGF19
      and FGF21 were undetectable. CONCLUSIONS: These data indicate that EAT has more
      in common with VAT, suggesting similar metabolic potential. The human epigastric
      adipose depot could have a significant functional role in metabolic diseases and
      should be further investigated.

PMID- 23949616
TI  - Exercise in obese female rats has beneficial effects on maternal and male and
      female offspring metabolism.
AB  - BACKGROUND: Maternal obesity (MO) impairs maternal and offspring health.
      Mechanisms and interventions to prevent adverse maternal and offspring outcomes
      need to be determined. Human studies are confounded by socio-economic status
      providing the rationale for controlled animal data on effects of maternal
      exercise (MEx) intervention on maternal (F0) and offspring (F1) outcomes in MO.
      HYPOTHESIS: MO produces metabolic and endocrine dysfunction, increases maternal
      and offspring glucocorticoid exposure, oxidative stress and adverse offspring
      outcomes by postnatal day (PND) 36. MEx in part prevents these outcomes. METHODS:
      F0 female rats ate either control or obesogenic diet from weaning through
      lactation. Half of each group wheel ran (from day 90 of life through pregnancy
      beginning day 120) providing four groups (n=8/group)--(i) controls, (ii) obese,
      (iii) exercised controls and (iv) exercised obese. After weaning, PND 21, F1
      offspring ate a control diet. Metabolic parameters of F0 prepregnancy and end of
      lactation and F1 offspring at PND 36 were analyzed. RESULTS: Exercise did not
      change maternal weight. Before breeding, MO elevated F0 glucose, insulin,
      triglycerides, cholesterol, leptin, fat and oxidative stress. Exercise completely
      prevented the triglyceride rise and partially increases glucose, insulin,
      cholesterol and oxidative stress. MO decreased fertility, recovered by exercise.
      At the end of lactation, exercise returned all metabolic variables except leptin
      to control levels. Exercise partially prevented MO elevated corticosterone. F1
      offspring weights were similar at birth. At PND 36, MO increased F1 male but not
      female offspring leptin, triglycerides and fat mass. In controls, exercise
      reduced male and female offspring glucose, prevented the offspring leptin
      increase and partially the triglyceride rise. CONCLUSIONS: MEx before and during
      pregnancy has beneficial effects on the maternal and offspring metabolism and
      endocrine function occurring with no weight change in mothers and offspring
      indicating the importance of body composition rather than weight in evaluations
      of metabolic status.

PMID- 23949617
TI  - Longitudinal associations between depressive symptoms and body mass index in a 20
      year follow-up.
AB  - OBJECTIVE: Longitudinal studies have rarely investigated changes in depressive
      symptoms and indicators of obesity simultaneously, although it is often proposed
      that the positive relationship between depression and obesity is bidirectional.
      The present study examined the reciprocal nature of the relationship between
      depressive symptoms and body mass index (BMI) in a 20-year follow-up survey.
      METHODS: Participants of a Finnish cohort study in 1989 at 22 years (N=1656) were
      followed up at ages 32 (N=1262) and 42 (N=1155) with postal questionnaires. BMI
      was calculated on the basis of self-reported weight and height, and depressive
      symptoms were assessed using the short form of the Beck Depression Inventory.
      Latent growth models (LGM) and cross-lagged autoregressive models were used to
      determine prospective associations between depressive symptoms and BMI. RESULTS:
      LGM analyses indicated that men with higher initial levels of depressive symptoms
      experienced a faster rate of increase in BMI (beta=0.20, P<0.01). Among women,
      change in BMI or depressive symptoms was not predicted by the other construct,
      but initial levels of BMI and depressive symptoms as well as their rate of change
      correlated positively with each other (r=0.15 and 0.37, respectively). In cross
      lagged models, depressive symptoms at age 32 predicted greater BMI at 42
      (beta=0.10, P<0.001) among men, whereas women with higher BMI at age 32 were more
      likely to have more depressive symptoms at 42 (beta=0.08, P<0.05). CONCLUSIONS:
      Elevated depressive symptoms predicted weight gain in men, while changes in
      depressive symptoms and body weight occurred concurrently in women. Tentative
      evidence showed that women with excess body weight were more likely to have
      increased symptoms of depression 10 years later. More emphasis should be placed
      on depressive symptoms in weight control programs as well as on reducing weight
      based stigmatization and discrimination in society.

PMID- 23949618
TI  - Orthogeriatrics: hip fracture and its implications.

PMID- 23949619
TI  - Extracorporeal membrane oxygenation for the treatment of acute respiratory
      failure due to respiratory syncytial virus after congenital heart surgery.
AB  - Mechanical circulatory support using extracorporeal membrane oxygenation is a
      therapeutic option for intractable cardiac or respiratory failure. It has widely
      been used for adult and pediatric patient population with considerable success in
      cases with otherwise dismal prognosis. We describe the successful use of
      extracorporeal membrane oxygenation in a 9-month-old patient suffering from a
      virus-related respiratory failure after congenital cardiac surgery. 

PMID- 23949620
TI  - AVX-470: a novel oral anti-TNF antibody with therapeutic potential in
      inflammatory bowel disease.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of
      the gastrointestinal tract, which is currently treated with injected monoclonal
      antibodies specific for tumor necrosis factor (TNF). We developed and
      characterized AVX-470, a novel polyclonal antibody specific for human TNF. We
      evaluated the oral activity of AVX-470m, a surrogate antibody specific for murine
      TNF, in several well-accepted mouse models of IBD. METHODS: AVX-470 and AVX-470m
      were isolated from the colostrum of dairy cows that had been immunized with TNF.
      The potency, specificity, and affinity of both AVX-470 and AVX-470m were
      evaluated in vitro and compared with infliximab. AVX-470m was orally administered
      to mice either before or after induction of colitis, and activity was measured by
      endoscopy, histopathology, immunohistochemistry, and quantitative measurement of
      messenger RNA levels. Colitis was induced using either 2,4,6-trinitrobenzene
      sulfonate or dextran sodium sulfate. RESULTS: AVX-470 and AVX-470m were shown to
      be functionally comparable in vitro. Moreover, the specificity, neutralizing
      potency, and affinity of AVX-470 were comparable with infliximab. Orally
      administered AVX-470m effectively reduced disease severity in several mouse
      models of IBD. Activity was comparable with that of oral prednisolone or
      parenteral etanercept. The antibody penetrated the colonic mucosa and inhibited
      TNF-driven mucosal inflammation with minimal systemic exposure. CONCLUSIONS: AVX
      470 is a novel polyclonal anti-TNF antibody with an in vitro activity profile
      comparable to that of infliximab. Oral administration of a surrogate antibody
      specific for mouse TNF is effective in treating mouse models of IBD, delivering
      the anti-TNF to the site of inflammation with minimal systemic exposure.

PMID- 23949621
TI  - Severity of fecal urgency and incontinence in inflammatory bowel disease:
      clinical, manometric and sonographic predictors.
AB  - BACKGROUND: Fecal incontinence (FI) and urgency are prevalent symptoms in
      patients with inflammatory bowel diseases (IBD). It is unclear which factors
      determine their severity. We evaluated associations of clinical activity,
      anorectal motility, and endoanal sonography with FI severity in IBD. METHODS:
      Fifty-eight consecutive IBD patients and 14 healthy volunteers participated in a
      cross-sectional, tertiary-center study. Active disease was defined as Crohn's
      disease activity index >= 150 and as simple clinical colitis index > 2. We
      assessed anal pressures and fatigue rate index (FRI) of the external anal
      sphincter (EAS) by manometry, rectal compliance and sensitivity by balloon
      distension, and sphincter defects by endoanal ultrasound. Significant bivariate
      associations between these parameters and the fecal incontinence severity scale
      (FISS) were evaluated in multivariate analysis. RESULTS: Twenty-seven patients
      (47%) reported urgency, 13 of which (22%) reported FI. Defects of the internal
      anal sphincter (IAS) and the EAS were diagnosed in 14 (24%) and 13 patients
      (22%), respectively. Patients had significantly lower rectal compliance and FRI
      compared with controls. FISS demonstrated significant bivariate associations with
      clinical disease activity (P = 0.0115), FRI (P = 0.0018), sonographic IAS and EAS
      defects (P < 0.0001 and 0.0059), rectal compliance (P = 0.0001), and volume at
      the threshold of a constant urge (Vurge, P = 0.0002). In multivariate analysis,
      FISS was associated with clinical disease activity (P = 0.0325), FRI (P =
      0.0367), Vurge (P = 0.0091), and sonographic IAS defect(s) (P = 0.0008). The
      derived model explained 62% of the variance in FISS (P < 0.0001). CONCLUSIONS:
      Clinical disease activity and manometric and sonographic anorectal parameters are
      associated with FI severity in IBD. Prospective studies are warranted to evaluate
      their predictive value in continence outcomes.

PMID- 23949622
TI  - Functional polymorphisms in the regulatory regions of the VNN1 gene are
      associated with susceptibility to inflammatory bowel diseases.
AB  - BACKGROUND: Vanin-1 is an epithelial pantetheinase, which regulates intestinal
      inflammation in mouse. We investigated whether human VNN1 levels could be
      associated to the susceptibility to inflammatory bowel diseases (IBD) and
      explored the participation of PPARg to these processes. METHODS: We studied VNN1
      expression in colon biopsies from IBD patients. We investigated polymorphisms in
      the regulatory regions of the VNN1 gene and examined their genetic association
      with the disease. Functional relevance of these single-nucleotide polymorphisms
      (SNPs) was assayed, and we tested PPARg in nuclear complexes associated with
      specific VNN1 polymorphic sequences. In mouse, we examined Vanin-1 expression in
      gut and feces during dextran sulfate sodium-induced colitis and assayed the
      effect of PPARg on Vanin-1 regulation. RESULTS: VNN1 is expressed by enterocytes
      and is upregulated in IBD. Three SNPs are statistically associated to IBD. The
      regions containing these SNPs specifically bind nuclear complexes and are
      correlated with the VNN1 transcript abundance in colon in an allele-dependent
      manner. One rare SNP is associated to severe ulcerative colitis with strong VNN1
      and dropped PPARg levels. PPARg is involved in nuclear complexes that bound to
      VNN1 regulatory sites. Similarly, Vanin-1 is tightly regulated in the mouse gut
      in normal and colitis conditions and PPARg regulates its expression. CONCLUSIONS:
      VNN1 is a marker for IBD. Polymorphic positions in the VNN1 locus are direct
      targets for nuclear factors that might regulate the level of VNN1 in colon, and
      this could be linked to IBD susceptibility. It is hoped that modulating locally
      VNN1 expression or activity can be exploited to develop future therapeutic
      strategies against IBD.

PMID- 23949623
TI  - Utility of an open-source DICOM viewer software (OsiriX) to assess pulmonary
      fibrosis in systemic sclerosis: preliminary results.
AB  - To investigate the utility of an open-source Digital Imaging and Communication in
      Medicine viewer software-OsiriX-to assess pulmonary fibrosis (PF) in patients
      with systemic sclerosis (SSc). Chest high-resolution computed tomography (HRCT)
      examinations obtained from 10 patients with diagnosis of SSc were analysed by two
      radiologists adopting a standard semiquantitative scoring for PF. Pulmonary
      involvement was evaluated in three sections (superior, middle and inferior). For
      the assessment of the extension of PF, the adopted semiquantitative HRCT score
      ranged from 0 to 3 (0 = absence of PF; 1 = 1-20 % of lung section involvement; 2
      = 21-40 % of lung section involvement; 3 = 41-100 % of lung section involvement).
      Further, a quantitative assessment (i.e. parameters of distribution of lung
      attenuation such as kurtosis and mean lung attenuation) of PF was independently
      performed on the same sections by a rheumatologist, independently and blinded to
      radiologists' scoring, using OsiriX. The results obtained were compared with
      those of HRCT semiquantitative analysis. Intra-reader reliability of HRCT
      findings and feasibility of OsiriX quantitative segmentation was recorded. A
      significant association between the median values of kurtosis by both the
      quantitative OsiriX assessment and the HRCT semiquantitative analysis was found
      (p < 0.0001). Moreover, kurtosis correlated significantly with the mean lung
      attenuation (Spearman's rho = 0.885; p = 0.0001). An excellent intra-reader
      reliability of HRCT findings among both readers was obtained. A significant
      difference between the mean time spent on the OsiriX quantitative analysis (mean
      1.85 +/- SD 1.3 min) and the mean time spent by the radiologist for the HRCT
      semiquantitative assessment (mean 8.5 +/- SD 4.5 min, p < 0.00001) was noted. The
      study provides the new working hypothesis that OsiriX may be a useful and
      feasible tool to achieve a quantitative evaluation of PF in SSc patients.

PMID- 23949625
TI  - Reactive intermediates in catalytic alkenylation; pathways for Mizoroki-Heck,
      oxidative Heck and Fujiwara-Moritani reactions.
AB  - Several closely related palladium-catalysed reactions involve the addition of Pd
      C across an alkene, and subsequent beta-elimination of Pd-H to give a more
      substituted alkene. The Pd-C precursor, normally possessing an sp(2) carbon bound
      to palladium, can be formed in several different ways, leading to sub-classes of
      reaction based on a common principle and convergent outcomes. The reaction
      pathway can vary from simple to highly subtle depending on the nature of the
      reactants and the ligation of the catalyst. Mechanistic analysis provides results
      that elucidate the pathway and link the different reaction types. The
      identification of reactive intermediates by NMR, ES-MS and other spectroscopic
      techniques, or by less direct methods, is an integral part of the process. This
      Feature Article covers ligand-free palladium catalysis, including the
      contributions of the authors, and separates catalysis where ligands are involved
      into cationic and neutral pathways. 

PMID- 23949624
TI  - Diabetes mellitus and accompanying hyperlipidemia are independent risk factors
      for adhesive capsulitis: a nationwide population-based cohort study (version 2).
AB  - Previous case-control studies of Caucasian ethnicity have reported the
      association of adhesive capsulitis (AC) with diabetes mellitus (DM). To further
      investigate the risk of AC in subjects with DM in an Asian population, we
      performed the present cohort study featured the analyses of a randomly selected
      sub-dataset of one million individuals insured by the Taiwan National Health
      Insurance for the period spanning 1996-2008. The study and comparison cohorts
      consisted of 5,109 newly diagnosed diabetic patients and 20,473 randomly selected
      non-diabetic subjects aged >= 20 years in the year 2000. Both cohorts were
      followed up until December 2008 to measure AC incidence. We found that the
      incidence density of AC in the DM cohort was 3.08 times that of the comparison
      cohort (146.9 vs. 47.7 per 10,000 person-years), and rate ratios varied from 1.23
      to 4.98 by categorized sociodemographic factors and comorbidity. The hazard ratio
      (HR) of AC for DM subjects remained significantly higher than that for non-DM
      subjects (p < 0.001) in all models. The HR increased in older age-groups (p <
      0.001) and females (p < 0.001). Hyperlipidemia consistently increases the risk of
      AC in both univariate (HR = 2.67, 95% confidence interval (CI) 2.36-4.06) and
      multivariate analyses (HR = 1.29, 95% CI 1.11-1.49). In this eight-year study
      period, we found that DM and accompanying hyperlipidemia were independent risk
      factors for AC. The risks are higher for older-aged women. Findings in the
      present study help to identify high-risk patient groups to exercise early
      prevention of AC and enhance comprehensive care quality of DM subjects.

PMID- 23949626
TI  - Factor structure and psychometric properties of the Italian version of the
      Gambling Related Cognitions Scale (GRCS-I).
AB  - The past decade has witnessed an expanded accessibility and popularity of
      gambling worldwide, and in Italy the phenomenon significantly increased.
      Nevertheless, little is known about the role of gambling cognitions among Italian
      individuals, and few scales assessing problem gambling have been validated. The
      purpose of the present study was to examine and validate the Gambling Related
      Cognitions Scale-Italian version (GRCS-I), based on the 23-item Gambling Related
      Cognitions Scale (GRCS). Two-tailed t tests, ANOVA, MANOVA, Pearson's
      correlation, and multiple regression analyses were used for continuous variables,
      while chi(2) tests with Yates's correction for categorical variables. Cronbach's
      alpha was utilized to determine the internal consistency, and logistic regression
      analysis and the receiver operating characteristic curve analysis to determine
      discriminant validity. Principal axis factoring with Oblimin rotation was
      applied, and then confirmatory factor analysis was used to cross-validate the
      factor structures. We extracted a five-factor solution that accounted for 60 % of
      variance. All 23 items had communalities and factor loadings were satisfactory,
      and the factor structures were similar to the original version of the measure.
      The Cronbach's alpha coefficients were adequate, and concurrent and discriminant
      validities of the GRCS were also confirmed. GRCS-I presented good psychometric
      properties and it demonstrated good validity and reliability, providing a valid
      and suitable tool for the assessment of gambling related cognitions among Italian
      individuals.

PMID- 23949627
TI  - Decreasing operating potential for water electrolysis to hydrogen via local
      confinement of iron-based soft coordination suprapolymers.
AB  - Currently there is intense interest in decreasing the operating potential for
      hydrogen evolution in water electrolysis to considerably decrease the energy
      cost. In this work we report a significant decrease of the operating potential
      for hydrogen evolution from neutral water mediated by an iron based soft
      coordination polymer (Fe(III)-SCSP). The creation of a local acidic environment
      with a thickness in the range of ~40 nm on the surface of a glassy carbon
      electrode allows enrichment of H(+) on the GCE, so that the operating potentials
      were effectively decreased. This strategy thus generates a new paradigm for
      lowering the operating potential of hydrogen generation from neutral water
      without the use of additional acids and organic cosolvents.

PMID- 23949628
TI  - Psychosocial aspects of children and families of children treated with automated
      peritoneal dialysis.
AB  - BACKGROUND: The aim of this study was to analyze psychosocial aspects of chronic
      kidney disease (CKD) in children treated with automated peritoneal dialysis
      (APD). METHODS: The study assessed 41 children > 2 (range 2.1-18) years of age
      and their parents. Data concerning the illness and sociodemographic parameters
      were collected. Patients completed the Paediatric Quality of Life Inventory
      (PedsQL) and their parents the PedsQL-proxy version, General Health Questionnaire
      (GHQ-12), Berlin Social Support Scales (BSSS), and Caregiver's Burden Scale
      (CBS). RESULTS: Parents rated their children's overall health-related quality of
      life (QoL) as well as their physical and emotional functioning lower than the
      patients themselves. The majority of primary caregivers had a medium level of the
      total burden index in the CBS and higher values in the scales need for support
      and perceived available support than in the received support (BSSS). In the GHQ
      12, 51.2% of primary caregivers had scores >2 points, which indicated the
      possible occurrence of abnormal mental functioning. CONCLUSIONS: Financial
      support for patients' families is necessary. Parents who provide primary care to
      children on PD require, above all, emotional support and assistance in self
      fulfilment. More than half of them may have impaired mental function. There is
      the strong need to provide continuous psychological care for caregivers.
      Differences in perception of the children's activity in varied areas by the
      patients themselves and their caregivers may contribute to further problems
      within families.

PMID- 23949629
TI  - Trace elements in dialysis.
AB  - In end-stage chronic kidney disease (CKD), pediatric nephrologists must consider
      the homeostasis of the multiple water-soluble ions that are influenced by renal
      replacement therapy (RRT). While certain ions such as potassium and calcium are
      closely monitored, little is known about the handling of trace elements in
      pediatric dialysis. RRT may lead to accumulation of toxic trace elements, either
      due to insufficient elimination or due to contamination, or to excessive removal
      of essential trace elements. However, trace elements are not routinely monitored
      in dialysis patients and no mechanism for these deficits or toxicities has been
      established. This review summarizes the handling of trace elements, with
      particular attention to pediatric data. The best data describe lead and indicate
      that there is a higher prevalence of elevated lead (Pb, atomic number 82) levels
      in children on RRT when compared to adults. Lead is particularly toxic in
      neurodevelopment and lead levels should therefore be monitored. Monitoring of
      zinc (Zn, atomic number 30) and selenium (Se, atomic number 34) may be indicated
      in the monitoring of all pediatric dialysis patients to reduce morbidity from
      deficiency. Prospective studies evaluating the impact of abnormal trace elements
      and the possible therapeutic value of intervention are required. 

PMID- 23949631
TI  - Responses of proximal tubular cells to injury in congenital renal disease: fight
      or flight.
AB  - Most chronic kidney disease in children results from congenital or inherited
      disorders, which can be studied in mouse models. Following 2 weeks of unilateral
      ureteral obstruction (UUO) in the adult mouse, nephron loss is due to proximal
      tubular mitochondrial injury and cell death. In neonatal mice, proximal tubular
      cell death is delayed beyond 2 weeks of complete UUO, and release of partial UUO
      allows remodeling of remaining nephrons. Progressive cyst expansion develops in
      polycystic kidney disease (PKD), a common inherited renal disorder. The
      polycystic kidney and fibrosis (pcy)-mutant mouse (which develops late-onset PKD)
      develops thinning of the glomerulotubular junction in parallel with growth of
      cysts in adulthood. Renal insufficiency in nephropathic cystinosis, a rare
      inherited renal disorder, results from progressive tubular cystine accumulation.
      In the Ctns knockout mouse (a model of cystinosis), proximal tubular cells become
      flattened, with loss of mitochondria and thickening of tubular basement membrane.
      In each model, persistent obstructive or metabolic stress leads ultimately to the
      formation of atubular glomeruli. The initial "fight" response (proximal tubular
      survival) switches to a "flight" response (proximal tubular cell death) with
      ongoing oxidative injury and mitochondrial damage. Therapies should be directed
      at reducing proximal tubular mitochondrial oxidative injury to enhance repair and
      regeneration.

PMID- 23949630
TI  - Solid organ transplantation following end-organ failure in recipients of
      hematopoietic stem cell transplantation in children.
AB  - Hematopoietic stem cell transplantation (HSCT) is an accepted treatment modality
      for various malignant and non-malignant disorders of the lympho-hematopoietic
      system. Patient survival rate has increased significantly with the use of this
      procedure. However, with the increase in disease-free patient survival rates,
      complications including various organ toxicities are also common. Kidney, liver,
      lung, heart, and skin are among those solid organs that are commonly affected and
      frequently lead to organ dysfunction and eventually end-organ disease.
      Conservative measures may or may not be successful in managing the organ failure
      in these patients. Solid organ transplantation has been shown to be promising in
      those patients who fail conservative management. This review will summarize the
      causes of solid organ (kidney, liver, and lung) dysfunction and the available
      data on transplantation of these solid organs in post-HSCT recipients. 

PMID- 23949632
TI  - Contemporary management of stage I and II seminoma.
AB  - Seminoma represents about 60 % of all testicular germ cell tumors. At
      presentation about 80 % of patients have stage I and about 15 % have stage II
      disease. The last three decades have seen a substantial change in the philosophy
      of management with the success of surveillance as a strategy to minimize
      unnecessary treatment, recognition of the late effects of radiation therapy, and
      the success of cisplatin-based chemotherapy as curative treatment either in the
      first-line or salvage setting. Overall, in stage I disease where 80-85 % are
      cured with orchiectomy alone, efforts now are directed at reducing the burden of
      the disease and its diagnosis on patients with increasing utilization of
      surveillance and decreased employment of adjuvant therapy. For stage II disease,
      balancing the relative toxicities of radiation and chemotherapy while avoiding
      the use of multimodality therapy due to the additive long-term toxicity has
      become the priority. 

PMID- 23949633
TI  - Using synchrotron radiation-based infrared microspectroscopy to reveal
      microchemical structure characterization: frost damaged wheat vs. normal wheat.
AB  - This study was conducted to compare: (1) protein chemical characteristics,
      including the amide I and II region, as well as protein secondary structure; and
      (2) carbohydrate internal structure and functional groups spectral intensities
      between the frost damaged wheat and normal wheat using synchrotron radiation
      based Fourier transform infrared microspectroscopy (SR-FTIRM). Fingerprint
      regions of specific interest in our study involved protein and carbohydrate
      functional group band assignments, including protein amide I and II (ca. 1774
      1475 cm(-1)), structural carbohydrates (SCHO, ca. 1498-1176 cm(-1)), cellulosic
      compounds (CELC, ca. 1295-1176 cm(-1)), total carbohydrates (CHO, ca. 1191-906
      cm(-1)) and non-structural carbohydrates (NSCHO, ca. 954-809 cm(-1)). The results
      showed that frost did cause variations in spectral profiles in wheat grains.
      Compared with healthy wheat grains, frost damaged wheat had significantly lower
      (p < 0.05) spectral intensities in height and area ratios of amide I to II and
      almost all the spectral parameters of carbohydrate-related functional groups,
      including SCHO, CHO and NSCHO. Furthermore, the height ratio of protein amide I
      to the third peak of CHO and the area ratios of protein amide (amide I + II) to
      carbohydrate compounds (CHO and SCHO) were also changed (p < 0.05) in damaged
      wheat grains. It was concluded that the SR-FTIR microspectroscopic technique was
      able to examine inherent molecular structure features at an ultra-spatial
      resolution (10 * 10 MUm) between different wheat grains samples. The structural
      characterization of wheat was influenced by climate conditions, such as frost
      damage, and these structural variations might be a major reason for the decreases
      in nutritive values, nutrients availability and milling and baking quality in
      wheat grains.

PMID- 23949634
TI  - Endogenous protease nexin-1 protects against cerebral ischemia.
AB  - The serine protease thrombin plays a role in signalling ischemic neuronal death
      in the brain. Paradoxically, endogenous neuroprotective mechanisms can be
      triggered by preconditioning with thrombin (thrombin preconditioning, TPC),
      leading to tolerance to cerebral ischemia. Here we studied the role of thrombin's
      endogenous potent inhibitor, protease nexin-1 (PN-1), in ischemia and in
      tolerance to cerebral ischemia induced by TPC. Cerebral ischemia was modelled in
      vitro in organotypic hippocampal slice cultures from rats or genetically
      engineered mice lacking PN-1 or with the reporter gene lacZ knocked into the PN-1
      locus PN-1HAPN-1-lacZ/HAPN-1-lacZ (PN-1 KI) exposed to oxygen and glucose
      deprivation (OGD). We observed increased thrombin enzyme activity in culture
      homogenates 24 h after OGD. Lack of PN-1 increased neuronal death in the CA1,
      suggesting that endogenous PN-1 inhibits thrombin-induced neuronal damage after
      ischemia. OGD enhanced beta-galactosidase activity, reflecting PN-1 expression,
      at one and 24 h, most strikingly in the stratum radiatum, a glial cell layer
      adjacent to the CA1 layer of ischemia sensitive neurons. TPC, 24 h before OGD,
      additionally increased PN-1 expression 1 h after OGD, compared to OGD alone. TPC
      failed to induce tolerance in cultures from PN-1(-/-) mice confirming PN-1 as an
      important TPC target. PN-1 upregulation after TPC was blocked by the c-Jun N
      terminal kinase (JNK) inhibitor, L-JNKI1, known to block TPC. This work suggests
      that PN-1 is an endogenous neuroprotectant in cerebral ischemia and a potential
      target for neuroprotection.

PMID- 23949636
TI  - Consultations with complementary and alternative medicine practitioners amongst
      wider care options for back pain: a study of a nationally representative sample
      of 1,310 Australian women aged 60-65 years.
AB  - Back pain is a significant health service issue in Australia and internationally.
      Back pain sufferers can draw upon a range of health care providers including
      complementary and alternative medicine (CAM) practitioners. Women are higher
      users of health services than men and tend to use CAM frequently for
      musculoskeletal conditions. However, there remain important gaps in our
      understanding of women's consultation patterns with CAM practitioners for back
      pain. The objective of this study is to examine the prevalence of use and
      characteristics of women who use CAM practitioners for back pain. The method used
      was a survey of a nationally representative sample of women aged 60-65 years from
      the Australian Longitudinal Study on Women's Health. Women consulted a massage
      therapist (44.1 %, n = 578) and a chiropractor (37.3 %, n = 488) more than other
      CAM practitioners for their back pain. Consultations with a chiropractor for back
      pain were lower for women who consulted a General Practitioner (GP) (OR, 0.56; 95
      % CI 0.41, 0.76) or a physiotherapist (OR, 0.53; 95 % CI 0.39, 0.72) than for
      those who did not consult a GP or a physiotherapist. CAM practitioner
      consultations for back pain were greater for women who visited a pharmacist (OR,
      1.99; 95 % CI 1.23, 3.32) than for women who did not visit a pharmacist. There is
      substantial use of CAM practitioners alongside conventional practitioners amongst
      women for back pain, and there is a need to provide detailed examination of the
      communication between patients and their providers as well as across the diverse
      range of health professionals involved in back pain care.

PMID- 23949635
TI  - The effects of nanomaterials as endocrine disruptors.
AB  - In recent years, nanoparticles have been increasingly used in several industrial,
      consumer and medical applications because of their unique physico-chemical
      properties. However, in vitro and in vivo studies have demonstrated that these
      properties are also closely associated with detrimental health effects. There is
      a serious lack of information on the potential nanoparticle hazard to human
      health, particularly on their possible toxic effects on the endocrine system.
      This topic is of primary importance since the disruption of endocrine functions
      is associated with severe adverse effects on human health. Consequently, in order
      to gather information on the hazardous effects of nanoparticles on endocrine
      organs, we reviewed the data available in the literature regarding the endocrine
      effects of in vitro and in vivo exposure to different types of nanoparticles. Our
      aim was to understand the potential endocrine disrupting risks posed by
      nanoparticles, to assess their underlying mechanisms of action and identify areas
      in which further investigation is needed in order to obtain a deeper
      understanding of the role of nanoparticles as endocrine disruptors. Current data
      support the notion that different types of nanoparticles are capable of altering
      the normal and physiological activity of the endocrine system. However, a
      critical evaluation of these findings suggests the need to interpret these
      results with caution since information on potential endocrine interactions and
      the toxicity of nanoparticles is quite limited. 

PMID- 23949637
TI  - Reduced numbers of regulatory B cells are negatively correlated with disease
      activity in patients with new-onset rheumatoid arthritis.
AB  - This study is aimed at determining the numbers of circulating Treg and Breg cells
      in patients with new-onset rheumatoid arthritis and during subsequent drug
      therapies. Patients were treated orally with 10 mg methotrexate weekly, and 20 mg
      leflunomide and 60 mg common threewingnut root daily (Lei Gong Teng) for 12
      weeks, but received no steroid therapy. Basal measurements were performed of
      serum C-reactive protein, anticyclic citrullinated peptide antibody, and
      erythrocyte sedimentation rate, and the numbers of cluster of differentiation
      CD4(+)CD25(+)Foxp3(+) T cells, interleukin 10 (IL10)-expressing on CD5(+)CD1d(+)
      and TIM1(+) B cells. Compared with the healthy controls, patients exhibited
      significantly less numbers of circulating CD19(+)TIM1(+)IL10(+),
      CD19(+)CD5(+)CD1d(+)IL10(+) B cells and CD4(+)CD25(+)Foxp3(+) T cells (P < 0.001,
      all). Drug therapy modulated the balance of different subsets of Breg and Treg
      cells. The numbers of CD19(+)TIM1(+)IL10(+) and CD19(+)CD5(+)CD1d(+)IL10(+) B
      cells correlated positively with the numbers of CD4(+)CD25(+)Foxp3(+) T cells in
      these patients (r = 0.707, P = 0.001; r = 0.481, P = 0.007, respectively). The
      values of DAS28 were negatively correlated with the numbers of
      CD19(+)TIM1(+)IL10(+) and CD19(+)CD5(+)CD1d(+)IL10(+) B cells, and
      CD4(+)CD25(+)Foxp3(+) T cells (r = -0.533, P = 0.023; r = -0.442, P = 0.016; and
      r = -0.444, P = 0.014, respectively). Of note, TIM1(+) B cells identified more
      circulating IL10(+) B cells than CD5(+)CD1d(+) B cells. Our data indicate that
      Breg and Treg cells have a potentially crucial role in controlling disease
      activity in rheumatoid arthritis patients, and TIM1(+) Breg cells may be a viable
      therapeutic target for these patients.

PMID- 23949638
TI  - Accuracy of Holladay 2 formula using IOLMaster parameters in the absence of lens
      thickness value.
AB  - BACKGROUND: The accuracy of the Holladay 2 (H2) formula is well-documented. This
      formula requires seven variables to estimate effective lens position (ELP) for
      the IOL power calculation. The lens thickness (LT) value is one of the required
      variables. Interestingly, the IOLMaster, which is one of the most commonly used
      optical biometers, can provide all the required ocular variables except LT value.
      It has become a pertinent issue to evaluate the accuracy of theH2 formula when it
      is used without the LT value. The purpose of this study was to evaluate the
      results when using the H2 formula, without the LT value, and compare such results
      to those obtained using the Haigis formula and the Hoffer Q formula. METHODS: The
      Institutional review board (IRB) gave their approval for the conduct of this
      prospective comparative study. One hundred and sixty-three eyes of 143 cataract
      patients from the Ophthalmology Department, Siriraj Hospital, Thailand were
      recruited. All eyes were measured using the IOLMaster (Carl Zeiss Meditec, Jena,
      Germany) for keratometry (K), axial length (AL), anterior chamber depth (ACD),
      and horizontal white-to-white (WTW) corneal diameter. Then, the LT measurement
      was obtained by A-scan ultrasonography (Quantel Axis-II, Quantel Medical, USA).
      Every patient underwent uncomplicated phacoemulsification by a single surgeon
      (NC) with a single technique using a single IOL model. Post-operative refraction
      was obtained at 3 months. The mean absolute errors (MAEs), median absolute errors
      (MedAEs) and percentage of the eyes within +/-0.25, +/-0.50, and +/-1.00 D of
      predicted refraction was calculated for H2 formula both with and without LT
      input, Haigis, and Hoffer Q formula. The results were also classified into a
      group of short AL (<22.0 mm), average AL (22.0 to 24.5 mm) and long AL (>24.5
      mm). RESULTS: There was no statistically significant difference in either MAEs or
      MedAEs of all formulas in all AL groups including the H2 with and without LT.
      There was a trend toward lower MAEs and MedAEs for H2 in the long AL group.
      Percentage of the eyes within +/-0.25, +/-0.50, and +/-1.00 D of predicted
      refraction were similar in all AL groups. CONCLUSION: The preliminary results of
      this study showed that the H2 formula performed well even without the LT value.
      It was comparable to the Haigis and Hoffer Q formulas.

PMID- 23949639
TI  - Comparison of cornea endothelial cell counts after combined phacovitrectomy
      versus pars plana vitrectomy with fragmentation.
AB  - BACKGROUND: To compare postoperative cornea endothelial cell loss between
      combined phacovitrectomy and pars plana vitrectomy (PPV) with fragmentation.
      METHODS: Eighty-eight consecutive patients (92 eyes) who underwent combined
      phacovitrectomy (53 eyes from 50 patients) or PPV with fragmentation (39 eyes
      from 38 patients) were enrolled in this retrospective study. Endothelial cell
      density (ECD) was calculated with specular microscopy at 1 and 3 months after
      surgery. RESULTS: At 3 months after surgery, the mean ECD decreased significantly
      from 2,646 +/- 296 cells/mm(2) to 2,422 +/- 347 cells/mm(2) in the combined
      phacovitrectomy group (P < 0.001). However, the PPV with fragmentation group did
      not show any significant changes in ECD during the same period (from 2,123 +/-
      628 cells/mm(2) to 2,073 +/- 574 cells/mm(2)). The mean endothelial cell loss in
      the combined phacovitrectomy group (7.9 and 9.5 %) was significantly higher than
      that in the PPV with fragmentation group (0.7 and 2.4 %) both at 1 and 3 months
      postoperatively (P = 0.001 and P = 0.001 respectively). CONCLUSION: In this
      study, corneal endothelial cell loss during the early postoperative period was
      significantly higher after combined phacovitrectomy than after PPV with
      fragmentation.

PMID- 23949640
TI  - Optimizing screening for tuberculosis and hepatitis B prior to starting tumor
      necrosis factor-alpha inhibitors in Crohn's disease.
AB  - BACKGROUND AND AIMS: Treatment with tumor necrosis factor-alpha (TNF-alpha)
      inhibitors in patients with Crohn's disease (CD) is associated with potentially
      serious infections, including tuberculosis (TB) and hepatitis B virus (HBV). We
      assessed the cost-effectiveness of extensive TB screening and HBV screening prior
      to initiating TNF-alpha inhibitors in CD. METHODS: We constructed two Markov
      models: (1) comparing tuberculin skin test (TST) combined with chest X-ray
      (conventional TB screening) versus TST and chest X-ray followed by the interferon
      gamma release assay (extensive TB screening) in diagnosing TB; and (2) HBV
      screening versus no HBV screening. Our base-case included an adult CD patient
      starting with infliximab treatment. Input parameters were extracted from the
      literature. Direct medical costs were assessed and discounted following a third
      party payer perspective. The main outcome was the incremental cost-effectiveness
      ratio (ICER). Sensitivity and Monte Carlo analyses were performed over wide
      ranges of probability and cost estimates. RESULTS: At base-case, the ICERs of
      extensive screening and HBV screening were ?64,340 and ?75,760 respectively to
      gain one quality-adjusted life year. Sensitivity analyses concluded that
      extensive TB screening was a cost-effective strategy if the latent TB prevalence
      is more than 12 % or if the false positivity rate of TST is more than 20 %. HBV
      screening became cost-effective if HBV reactivation or HBV-related mortality is
      higher than 37 and 62 %, respectively. CONCLUSIONS: Extensive TB screening and
      HBV screening are not cost-effective compared with conventional TB screening and
      no HBV screening, respectively. However, when targeted at high-risk patient
      groups, these screening strategies are likely to become cost-effective.

PMID- 23949641
TI  - Angiotensin converting enzyme-inhibitor reduces colitis severity in an IL-10
      knockout model.
AB  - BACKGROUND: We previously demonstrated angiotensin converting enzymes (ACE) over
      expression in a dextran-sodium sulfate colitis model; ACE inhibitor (ACE-I)
      treatment reduced colitis severity in this model. However, ACE-I has not been
      tested in more immunologically relevant colitis models. AIM: We hypothesized that
      ACE-I would decrease disease severity in an IL-10 knockout (-/-) colitis model.
      METHODS: Colitis was induced by giving 10-week old IL-10-/- mice piroxicam (P.O.)
      for 14 days. The ACE-I enalaprilat was given transanally at a dose of 6.25 mg/kg
      for 21 days. Prednisolone (PSL) with or without enalaprilat were used as
      therapeutic, comparative groups. All groups were compared to a placebo treated
      group. Outcome measures were clinical course, histology, abundance of pro
      inflammatory cytokines/chemokines, and epithelial barrier function. RESULTS:
      Enalaprilat exhibited better survival (91 %) versus other treatment groups (PSL:
      85.7 %, PSL + ACE-I: 71.4 %, placebo: 66.6 %). The ACE-I and PSL + ACE-I groups
      showed significantly better histological scores versus placebo mice. ACE-I and
      the PSL groups significantly reduced several pro-inflammatory cytokines versus
      placebo mice. FITC-dextran permeability was reduced in the ACE-I and PSL + ACE-I
      groups. Blood pressure was not affected in ACE-I treated mice compared to placebo
      mice. CONCLUSIONS: ACE-I was effective in reducing severity of colitis in an IL
      10-/- model. The addition of prednisolone minimally augmented this effect. The
      findings suggest that appropriately dosed ACE-I with or without steroids may be a
      new therapeutic agent for colitis.

PMID- 23949642
TI  - Effects of Cd, Zn and Cd + Zn combination on ATPase activitiy in the gill and
      muscle of tilapia (Oreochromis niloticus).
AB  - This study investigated the responses of Na(+)/K(+)-ATPase, Mg(2+)-ATPase and
      Ca(2+)-ATPase in the gill and muscle of a freshwater fish Oreochromis niloticus
      exposed to 1 MUg/mL of Cd and Zn and their mixture for different periods (0, 7,
      14, 21 and 28 days). At the end of experimental periods, the activities
      Na(+)/K(+)-ATPase, Mg(2+)-ATPase and Ca(2+)-ATPase in gill tissues and only
      Ca(2+)-ATPase activity in muscle tissues were measured. Gill Na(+)/K(+)-ATPase
      activity generally decreased following single metal exposures, whereas their
      combinations increased its activity. Gill Ca(2+)-ATPase activity decreased
      relative to the control at most exposure times for single exposures of Zn and Cd,
      as well as for the combined exposure. There was no gill Ca(2+)-ATPase activity
      after 28 days of exposure to Zn and Cd combined. Mg(2+)-ATPase activity was not
      affected significantly in gill tissue by exposure to Zn and Cd individually or in
      combination. Muscle Ca(2+)-ATPase activity also decreased significantly following
      metal exposure, but not as greatly as in the gill tissue. Tissue protein levels
      were mostly unaffected by metal exposures. This study showed that certain ATPases
      are highly sensitive to metal exposure whether the metals are essential or non
      essential, and suggests using gill tissue Na(+)/K(+)-ATPase and Ca(2+)-ATPase as
      sensitive biomarkers in metal contaminated waters.

PMID- 23949643
TI  - Prostate positioning using cone-beam computer tomography based on manual soft
      tissue registration: interobserver agreement between radiation oncologists and
      therapists.
AB  - PURPOSE: To check the interobserver agreement between radiation oncologists and
      therapists (RTT) using an on- and off-line cone-beam computer tomography (CBCT)
      protocol for setup verification in the radiotherapy of prostate cancer. MATERIALS
      AND METHODS: The CBCT data from six prostate cancer patients treated with
      hypofractionated intensity-modulated radiotherapy (IMRT) were independently
      reviewed off-line by four observers (one radiation oncologist, one junior and two
      senior RTTs) and benchmarked with on-line CBCT positioning performed by a
      radiation oncologist immediately prior to treatment. CBCT positioning was based
      on manual soft-tissue registration. Agreement between observers was evaluated
      using weighted Cohen's kappa statistics. RESULTS: In total, 152 CBCT-based
      prostate positioning procedures were reviewed by each observer. The mean (+/-
      standard deviation) of the differences between off- and on-line CBCT-simCT
      registration translations along the three directions (antero-posterior, latero
      lateral and cranio-caudal) and rotation around the antero-posterior axis were 
      0.7 (3.6) mm, 1.9 (2.7) mm, 0.9 (3.6) mm and -1.8 (5.0) degrees, respectively.
      Satisfactory interobserver agreement was found, being substantial (weighted kappa
      >0.6) in 10 of 16 comparisons and moderate (0.41-0.60) in the remaining six
      comparisons. CONCLUSIONS: CBCT interpretation performed by RTTs is comparable to
      that of radiation oncologists. Our study might be helpful in the quality
      assurance of radiotherapy and the optimization of competencies. Further
      investigation should include larger sample sizes, a greater number of observers
      and validated methodology in order to assess interobserver variability and its
      impact on high-precision prostate cancer IGRT. In the future, it should enable
      the wider implementation of complex and evolving radiotherapy technologies.

PMID- 23949644
TI  - [Second primary cancers after radiotherapy in breast cancer patients].

PMID- 23949645
TI  - Interventions to improve the physical function of ICU survivors: a systematic
      review.
AB  - BACKGROUND: ICU admissions are ever increasing across the United States.
      Following critical illness, physical functioning (PF) may be impaired for up to 5
      years. We performed a systematic review of randomized controlled trials
      evaluating the efficacy of interventions targeting PF among ICU survivors. The
      objective of this study was to identify effective interventions that improve long
      term PF in ICU survivors. METHODS: MEDLINE, Excerpta Medica Database (EMBASE),
      Cumulative Index to Nursing and Allied Health Literature (CINAHL), and
      Physiotherapy Evidence-Based Database (PEDro) were searched between 1990 and
      2012. Two reviewers independently evaluated studies for eligibility, critically
      appraised the included studies, and extracted data into standardized evidence
      tables. RESULTS: Fourteen studies met the inclusion criteria. Interventions
      included exercise/physical therapy (PT), parenteral nutrition, nurse-led follow
      up, spontaneous awakening trials, absence of sedation during mechanical
      ventilation, and early tracheotomy. Nine studies failed to demonstrate efficacy
      on PF of the ICU survivors. However, early physical exercise and PT-based
      interventions had a positive effect on long-term PF. CONCLUSIONS: The only
      effective intervention to improve long-term PF in critically ill patients is
      exercise/PT; its benefit may be greater if started earlier. Further research in
      this area comparing different interventions and timing is needed.

PMID- 23949646
TI  - Dollfusiella Campbell & Beveridge, 1994 (Trypanorhyncha: Eutetrarhynchidae) from
      elasmobranchs off Borneo, including descriptions of five new species.
AB  - Sampling of a large number of elasmobranchs from coastal waters off Borneo
      revealed the presence of five new species of Dollfusiella Campbell & Beveridge,
      1994 (Trypanorhyncha: Eutetrarhynchidae), namely D. angustiformis n. sp., D.
      hemispinosa n. sp., D. spinosa n. sp., D. imparispinis n. sp. and D. parva n. sp.
      Dollfusiella angustiformis n. sp. is described from the spiral intestines of four
      species of the dasyatid stingray genus Himantura Muller & Henle from both the
      Indonesian and Malaysian parts of Borneo. All the other species were obtained
      from Malaysian Borneo. Dollfusiella hemispinosa n. sp. is described from the
      spiral intestines of three species of Himantura, whereas D. spinosa n. sp. was
      obtained from several specimens of Pastinachus solocirostris Last, Manjaji &
      Yearsley (Dasyatidae) as well as from Taeniura lymma 1 (sensu Naylor et al.,
      2012) (Dasyatidae), Neotrygon kuhlii 2 (sensu Naylor et al., 2012) (Dasyatidae),
      and Glaucostegus cf. typus (sensu Naylor et al., 2012) (Rhinobatidae).
      Dollfusiella imparispinis n. sp. is described from the spiral intestine of a
      single specimen of Chiloscyllium punctatum Muller & Henle (Hemiscyllidae) from
      the South China Sea off Sarawak, whereas D. parva n. sp. was obtained from
      several species of Himantura. Specimens of the five novel taxa possess scoleces
      covered with enlarged microtriches, a morphological characteristic exhibited by
      several other congeners. However, the new species differ from all congeners by
      possessing unique patterns of oncotaxy as well as combinations of additional
      morphological features. The number of valid species within Dollfusiella is
      increased to 26. For this reason, a key for the species of Dollfusiella is
      provided. Furthermore, novel information on hosts and geographic distribution is
      provided for two previously described species of Dollfusiella, D. michiae
      (Southwell, 1929) and D. spinulifera (Beveridge & Jones, 2000). The latter
      species differs slightly from the original description and shows a much higher
      variability with regard to the lengths of the scolex and muscular bulbs and the
      number of testes. These variable characters subdivided specimens of D.
      spinulifera into relatively distinct groups. However, the specimens did not
      differ in their oncotaxy and are considered to represent a single variable
      species. 

PMID- 23949647
TI  - Two philometrids (Nematoda: Philometridae) infecting the tigertooth croaker
      Otolithes ruber (Bloch & Schneider) (Teleostei: Sciaenidae) off Iran, including
      erection of a new genus.
AB  - Two philometrid nematodes (Philometridae) are described from the marine perciform
      fish (tigertooth croaker) Otolithes ruber (Bloch & Schneider) (Sciaenidae) from
      off Iran: Clavinemoides annulatus n. g., n. sp. based on female specimens from
      the caudal fin of fish from the Persian Gulf and Philometra otolithi Moravec &
      Manoharan, 2013 from subgravid and nongravid females collected from the ovary of
      fishes in the Sea of Oman and the Persian Gulf. The monotypic genus Clavinemoides
      n. g. is mainly characterised by a triangular oral aperture, a markedly large
      anterior oesophageal bulb, a distinctly annulated body and numerous fine elevated
      transverse cuticular bands. The finding of P. otolithi in Iranian waters
      represents a new geographical record of this parasite species. An updated key to
      the genera of the Philometrinae Baylis & Daubney, 1926 is provided. 

PMID- 23949648
TI  - Sequence analysis of the internal transcribed spacer 2 (ITS2) from Philornis
      seguyi (Garcia, 1952) and Philornis torquans (Nielsen, 1913) (Diptera: Muscidae).
AB  - Philornis Meinert, 1890 (Diptera: Muscidae) is a genus of Neotropical dipterans
      that parasitise birds. The currently used external morphological characters to
      distinguish between species within this genus present some limitations. We used
      the second internal transcribed spacer region (ITS2) of the rRNA gene as a
      molecular marker to differentiate adult specimens of Philornis identified
      morphologically as Philornis torquans and Philornis seguyi from different
      localities. Specimens identified as P. seguyi from Magdalena (Buenos Aires
      Province) showed an ITS2 sequence different from that for P. torquans, whereas
      all other specimens of P. seguyi had sequences identical to those for P.
      torquans. These findings do not necessarily confirm that specimens from Magdalena
      indeed belong to P. seguyi, nor that P. seguyi is a valid species. Instead, they
      alert us about the potential for species misidentification when using
      morphological characters alone. The use of molecular approaches to aid the
      identification of Philornis spp. will shed light on the systematics of this
      group. P. torquans is reported for the first time in Mendoza Province and
      Uruguay. 

PMID- 23949649
TI  - A new species of Eimeria Schneider, 1875 (Apicomplexa: Eimeriidae) from Carlia
      spp. (Sauria: Scincidae) from Papua New Guinea.
AB  - A new species of Eimeria Schneider, 1875 from rainbow skinks, Carlia ailanpalai
      Zug and Carlia eothen Zug is described from specimens collected in Papua New
      Guinea (PNG). Oocysts of Eimeria zugi n. sp. from one of one (100%) C. eothen are
      ellipsoidal to cylindroidal, with a smooth, colourless, bi-layered wall, measure
      25.1 * 15.5 MUm and have a length/width ratio of 1.6. The micropyle and the
      oocyst residuum are absent, but a polar granule is present. The sporocysts are
      ovoidal to ellipsoidal and 10.3 * 7.1 MUm in size and do not contain Stieda, sub
      Stieda or para-Stieda bodies; and the sporocyst residuum is composed of a compact
      mass of large globules. The sporozoites are elongate, 12.8 * 2.9 MUm in size, and
      contain anterior and posterior refractile bodies with a nucleus between them.
      This is the ninth species of coccidium described from skinks from PNG, and the
      new species described herein is apparently endemic to the skink genus Carlia
      (Gray).

PMID- 23949650
TI  - Sawadalepis prima n. g., n. sp. (Cestoda: Cyclophyllidea) from the Schreiber's
      bent-winged bat Miniopterus schreibersii Kuhl (Chiroptera: Vespertilionidae) from
      China.
AB  - Sawadalepis n. g. is erected for Sawadalepis prima n. sp. in Schreiber's bent
      winged bat Miniopterus schreibersii Kuhl (Chiroptera: Vespertilionidae) from
      southern China. Diagnostic features of the currently monotypic genus include
      attributes of the osmoregulatory system and female genital organs. The dorsal
      osmoregulatory canals are shifted bilaterally towards the margins of proglottides
      in relation to the ventral canals. The genital pores are unilateral and
      sinistral. Among female attributes, the copulatory part of the vagina is covered
      externally by a dense layer of intensely stained cells; the conductive part of
      the vagina is clearly distinguishable from the seminal receptacle; the uterus has
      ventral and dorsal diverticula, extending bilaterally beyond the longitudinal
      osmoregulatory canals; and the eggs are spherical with thick outer coat. 

PMID- 23949651
TI  - Description of Rhabdias breviensis n. sp. (Rhabditoidea: Rhabdiasidae) in two
      Neotropical frog species.
AB  - Nematodes of the genus Rhabdias Stiles & Hassall, 1905 (Rhabditoidea:
      Rhabdiasidae) have a dioecious free-living stage and a hermaphroditic stage that
      parasitises the lungs of amphibians and reptiles. Approximately 94 species of
      Rhabdias have been described. Because the similar morphological characteristics
      such as the labial structures, the location of the vulva and the shape of the
      tail of Rhabdias spp. hinder their identification, molecular biology techniques
      and scanning electron microscopy have been employed to diagnose species of this
      genus. This study describes Rhabdias breviensis n. sp., parasitic in the lungs of
      two Neotropical frog species Leptodactylus petersii Steindachner and
      Leptodactylus macrosternum Miranda-Ribeiro. The description of this species
      integrates classical taxonomy, scanning electron microscopy and a molecular
      analysis of the mitochondrial COI gene. The new species differs from all other
      Rhabdias species parasitic in Neotropical hosts in certain morphometric
      parameters, the position of the vulva, the host group and the cephalic
      characters. 

PMID- 23949652
TI  - Revisiting the octopicolid copepods (Octopicolidae: Octopicola Humes, 1957):
      comparative morphology and an updated key to species.
AB  - A review of the present state of knowledge on the octopicolid copepods
      (Octopicolidae: Octopicola Humes, 1957) is presented. Characteristic
      morphological features are illustrated with scanning electron micrographs of
      Octopicola superba superba Humes, 1957. Comparative morphology analysis led to
      the conclusion that there is sufficient evidence to justify raising the two
      subspecies of O. superba to full species rank. A new identification key for the
      four species of Octopicola Humes, 1957, i.e. O. superba Humes, 1957, O.
      antillensis Stock, Humes & Gooding, 1963, O. stocki Humes, 1963 and O. regalis
      Humes, 1974, is proposed after evaluation of the morphological characters which
      vary more markedly between them. Among other characters, these species differ in
      the ornamentation of the third antennal segment, maxilla and male maxilliped.
      They are further distinguished by a combination of several character states
      concerning the fifth pedigerous somite. 

PMID- 23949653
TI  - Paradiscogaster flindersi and P. oxleyi n. sp. (Digenea: Faustulidae):
      overlapping host and geographical distributions in corallivore chaetodontid
      fishes in the tropical Indo-west Pacific.
AB  - A total of 2,868 individuals of 47 species of chaetodontids were examined for
      faustulids at seven major localities in the Tropical Indo-West Pacific (TIWP).
      Combined morphological and molecular analyses allowed us to describe
      Paradiscogaster oxleyi n. sp. from three localities in the TIWP and in three host
      species, Chaetodon lunulatus Quoy & Gaimard (type-host), C. ornatissimus Cuvier
      and C. meyeri Bloch & Schneider. Molecular analysis of the ITS2 region of rDNA
      from two host species and three localities supports the morphology-based
      conclusion that P. oxleyi n. sp. is the same species at the three localities.
      Paradiscogaster flindersi Bray, Cribb & Barker, 1994 is reported from three new
      localities in the TIWP and is now known from 13 chaetodontid species. Sequences
      from samples consistent with P. flindersi differed from those from P. oxleyi n.
      sp. in 11-12 base pairs. The host ranges of the two species overlap broadly.
      Neither species was found in French Polynesia but both were found at Swain Reefs
      on the Great Barrier Reef. Only one of the two species was found at each of the
      five other sites. Both species occur almost exclusively in specialist
      corallivores allowing the inference that the metacercariae occur in corals.
      Finally, a key to the species of Paradiscogaster is provided. 

PMID- 23949654
TI  - Management of the treatment delay in symptomatic carotid artery stenosis.
AB  - Saving time to intervention is crucial in patients with symptomatic carotid
      artery stenosis (SCAS). We introduced a fast-track protocol (FTP). Time frames
      from the onset of symptoms to intervention before and after the introduction of
      an FTP were analyzed. SCAS patients (403 patients/405 procedures) were evaluated
      according to whether surgery was performed before (group 1) or after (group 2)
      the introduction of the FTP. Time frames to surgery, causes of delay and
      frequency of recurrent events are reported. The median time delay decreased from
      17 to 12 days (p<0.001), but time to ultrasound examination remained unchanged.
      Surgery was within 2 weeks in 41% in group 1 and in 57% in group 2 (p=0.001). Of
      181 (30%) patients treated according to the FTP, 54 were operated within 7 days
      (median), and 80% had the intervention within 2 weeks. Time to surgery decreased
      significantly after the introduction of the FTP.

PMID- 23949655
TI  - Membrane-targeting approaches for enhanced cancer cell destruction with
      irreversible electroporation.
AB  - Irreversible electroporation (IRE) is a promising technology to treat local
      malignant cancer using short, high-voltage electric pulses. Unfortunately, in
      vivo studies show that IRE suffers from an inability to destroy large volumes of
      cancer tissue without introduction of cytotoxic agents and/or increasing the
      applied electrical dose to dangerous levels. This research will address this
      limitation by leveraging membrane-targeting mechanisms that increase lethal
      membrane permeabilization. Methods that directly modify membrane properties or
      change the pulse delivery timing are proposed that do not rely on cytotoxic
      agents. This work shows that significant enhancement (67-75% more cell
      destruction in vitro and >100% treatment volume increase in vivo) can be achieved
      using membrane-targeting approaches for IRE cancer destruction. The methods
      introduced are surfactants (i.e., DMSO) and pulse timing which are low cost, non
      toxic, and easy to be incorporated into existing clinical use. Moreover, when
      needed, these methods can also be combined with electrochemotherapy to further
      enhance IRE treatment efficacy. 

PMID- 23949656
TI  - Energy harvesting from the cardiovascular system, or how to get a little help
      from yourself.
AB  - Human energy harvesting is envisioned as a remedy to the weight, the size, and
      the poor energy density of primary batteries in medical implants. The first
      implant to have necessarily raised the idea of a biological power supply was the
      pacemaker in the early 1960s. So far, review articles on human energy harvesting
      have been rather unspecific and no tribute has been given to the early role of
      the pacemaker and the cardiovascular system in triggering research in the field.
      The purpose of the present article is to provide an up-to-date review of research
      efforts targeting the cardiovascular system as an alternative energy source for
      active medical implants. To this end, a chronological survey of the last 14 most
      influential publications is proposed. They include experimental and/or
      theoretical studies based on electromagnetic, piezoelectric, or electrostatic
      transducers harnessing various forms of energy, such as heart motion, pressure
      gradients, and blood flow. Technical feasibility does not imply clinical
      applicability: although most of the reported devices were shown to harvest an
      interesting amount of energy from a physiological environment, none of them were
      tested in vivo for a longer period of time. 

PMID- 23949657
TI  - Evaluation of mechanical properties of human mesenchymal stem cells during
      differentiation to smooth muscle cells.
AB  - Human mesenchymal stem cells (hMSCs) are multipotent cells appropriate for a
      variety of tissue engineering and cell therapy applications. Mechanical
      properties of hMSCs during differentiation are associated with their particular
      metabolic activity and regulate cell function due to alternations in cytoskeleton
      and structural elements. The objective of this study is to evaluate elastic and
      viscoelastic properties of hMSCs during long term cultivation in control and
      transforming growth factor-beta1 treatment groups using micropipette aspiration
      technique. The mean Young's modulus (E) of the control samples remained nearly
      unchanged during 6 days of cultivation, but that of the test samples showed an
      initial reduction compared to its relevant control sample after 2 days of
      treatment by biological growth factor, followed by a significant rise after 4 and
      6 days. The viscoelastic creep tests showed that both instantaneous and
      equilibrium moduli significantly increased with the treatment time and reached to
      maximum values of 622.9 +/- 114.2 and 144.3 +/- 11.6 Pa at the sixth day,
      respectively, while increase in apparent viscosity was not statistically
      significant. Such change of mechanical properties of hMSCs during specific
      lineage commitment contributes to regenerative medicine as well as stem-cell
      based therapy in which biophysical signals regulate stem cell fate.

PMID- 23949659
TI  - The association between n-3 polyunsaturated fatty acid levels in erythrocytes and
      the risk of rheumatoid arthritis in Korean women.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is one of the most common autoimmune
      diseases that result in chronic inflammation of the joints. n-3 polyunsaturated
      fatty acids (PUFAs) have been suggested to play a role in the pathogenesis and
      clinical course of RA. The purpose of the present study was to investigate
      whether erythrocyte levels of n-3 PUFA are associated with an increased risk of
      RA and whether this could potentially serve as an indicator of RA disease
      activity in Korean women. METHODS: A total of 100 female RA patients and 100
      healthy women were enrolled into this study. Erythrocyte fatty acid composition
      and RA disease activity were evaluated in all patients. RESULTS: Erythrocyte
      levels of alpha-linolenic acid (ALA; 18:3n3), eicosapentaenoic acid (EPA;
      20:5n3), and the omega-3 index [EPA + docosahexaenoic acid (DHA)] were
      significantly lower in RA patients than in healthy controls. Multivariable
      adjusted regression analysis showed that the levels of ALA, EPA, and the ratio of
      EPA to arachidonic acid were negatively associated with the risk of RA after
      adjusting for body weight and smoking status. Additionally, the concentration of
      prostaglandin E2 was significantly decreased with increased levels of erythrocyte
      DHA among RA patients. CONCLUSIONS: Erythrocyte levels of EPA and ALA were
      negatively associated with the risk of RA in Korean women, which may be related
      to eicosanoid metabolism.

PMID- 23949658
TI  - Overexpression in E. coli and purification of the L. pneumophila Lpp2981 protein.
AB  - The Lpp2981 gene from Legionella pneumophila, the causative agent of
      Legionnaire's disease, was cloned into the pMWT7 plasmid. The construct was used
      to express this gene in Escherichia coli. Five different bacterial strains were
      tested to overexpress the gene but without success. Sequence analysis revealed a
      cluster of four rare codons near the 5'-end of the gene. These codons were
      replaced with those commonly used in E. coli. The mutated Lpp2981 gene was
      successfully expressed in all the E. coli strains tested. The expressed protein
      (with an apparent molecular mass of 30 kDa) was collected in the insoluble
      fraction of the cell lysate, purified as inclusion bodies and functionally
      reconstituted into liposomes. The highest level of overexpression was obtained in
      E. coli C0214 after 6 h of induction with isopropyl-beta-D-thiogalactopyranoside
      at 37  degrees C, yielding 74 mg of purified protein per liter of culture. We
      conclude that the clustering of rare codons at the 5'-end of the open-reading
      frame is a critical factor for the heterologous expression of Lpp2981 in E. coli.

PMID- 23949660
TI  - Integrating metagenomic and amplicon databases to resolve the phylogenetic and
      ecological diversity of the Chlamydiae.
AB  - In the era of metagenomics and amplicon sequencing, comprehensive analyses of
      available sequence data remain a challenge. Here we describe an approach
      exploiting metagenomic and amplicon data sets from public databases to elucidate
      phylogenetic diversity of defined microbial taxa. We investigated the phylum
      Chlamydiae whose known members are obligate intracellular bacteria that represent
      important pathogens of humans and animals, as well as symbionts of protists.
      Despite their medical relevance, our knowledge about chlamydial diversity is
      still scarce. Most of the nine known families are represented by only a few
      isolates, while previous clone library-based surveys suggested the existence of
      yet uncharacterized members of this phylum. Here we identified more than 22,000
      high quality, non-redundant chlamydial 16S rRNA gene sequences in diverse
      databases, as well as 1900 putative chlamydial protein-encoding genes. Even when
      applying the most conservative approach, clustering of chlamydial 16S rRNA gene
      sequences into operational taxonomic units revealed an unexpectedly high species,
      genus and family-level diversity within the Chlamydiae, including 181 putative
      families. These in silico findings were verified experimentally in one Antarctic
      sample, which contained a high diversity of novel Chlamydiae. In our analysis,
      the Rhabdochlamydiaceae, whose known members infect arthropods, represents the
      most diverse and species-rich chlamydial family, followed by the protist
      associated Parachlamydiaceae, and a putative new family (PCF8) with unknown host
      specificity. Available information on the origin of metagenomic samples indicated
      that marine environments contain the majority of the newly discovered chlamydial
      lineages, highlighting this environment as an important chlamydial reservoir.

PMID- 23949661
TI  - Metaproteomics of cellulose methanisation under thermophilic conditions reveals a
      surprisingly high proteolytic activity.
AB  - Cellulose is the most abundant biopolymer on Earth. Optimising energy recovery
      from this renewable but recalcitrant material is a key issue. The metaproteome
      expressed by thermophilic communities during cellulose anaerobic digestion was
      investigated in microcosms. By multiplying the analytical replicates (65 protein
      fractions analysed by MS/MS) and relying solely on public protein databases, more
      than 500 non-redundant protein functions were identified. The taxonomic community
      structure as inferred from the metaproteomic data set was in good overall
      agreement with 16S rRNA gene tag pyrosequencing and fluorescent in situ
      hybridisation analyses. Numerous functions related to cellulose and hemicellulose
      hydrolysis and fermentation catalysed by bacteria related to Caldicellulosiruptor
      spp. and Clostridium thermocellum were retrieved, indicating their key role in
      the cellulose-degradation process and also suggesting their complementary action.
      Despite the abundance of acetate as a major fermentation product, key
      methanogenesis enzymes from the acetoclastic pathway were not detected. In
      contrast, enzymes from the hydrogenotrophic pathway affiliated to
      Methanothermobacter were almost exclusively identified for methanogenesis,
      suggesting a syntrophic acetate oxidation process coupled to hydrogenotrophic
      methanogenesis. Isotopic analyses confirmed the high dominance of the
      hydrogenotrophic methanogenesis. Very surprising was the identification of an
      abundant proteolytic activity from Coprothermobacter proteolyticus strains,
      probably acting as scavenger and/or predator performing proteolysis and
      fermentation. Metaproteomics thus appeared as an efficient tool to unravel and
      characterise metabolic networks as well as ecological interactions during
      methanisation bioprocesses. More generally, metaproteomics provides direct
      functional insights at a limited cost, and its attractiveness should increase in
      the future as sequence databases are growing exponentially. 

PMID- 23949662
TI  - Taxonomically and functionally diverse microbial communities in deep crystalline
      rocks of the Fennoscandian shield.
AB  - Microbial life in the nutrient-limited and low-permeability continental
      crystalline crust is abundant but remains relatively unexplored. Using high
      throughput sequencing to assess the 16S rRNA gene diversity, we found diverse
      bacterial and archaeal communities along a 2516-m-deep drill hole in continental
      crystalline crust in Outokumpu, Finland. These communities varied at different
      sampling depths in response to prevailing lithology and hydrogeochemistry.
      Further analysis by shotgun metagenomic sequencing revealed variable carbon and
      nutrient utilization strategies as well as specific functional and physiological
      adaptations uniquely associated with specific environmental conditions.
      Altogether, our results show that predominant geological and hydrogeochemical
      conditions, including the existence and connectivity of fracture systems and the
      low amounts of available energy, have a key role in controlling microbial ecology
      and evolution in the nutrient and energy-poor deep crustal biosphere. 

PMID- 23949663
TI  - Potential role of viruses in white plague coral disease.
AB  - White plague (WP)-like diseases of tropical corals are implicated in reef decline
      worldwide, although their etiological cause is generally unknown. Studies thus
      far have focused on bacterial or eukaryotic pathogens as the source of these
      diseases; no studies have examined the role of viruses. Using a combination of
      transmission electron microscopy (TEM) and 454 pyrosequencing, we compared 24
      viral metagenomes generated from Montastraea annularis corals showing signs of WP
      like disease and/or bleaching, control conspecific corals, and adjacent seawater.
      TEM was used for visual inspection of diseased coral tissue. No bacteria were
      visually identified within diseased coral tissues, but viral particles and
      sequence similarities to eukaryotic circular Rep-encoding single-stranded DNA
      viruses and their associated satellites (SCSDVs) were abundant in WP diseased
      tissues. In contrast, sequence similarities to SCSDVs were not found in any
      healthy coral tissues, suggesting SCSDVs might have a role in WP disease.
      Furthermore, Herpesviridae gene signatures dominated healthy tissues,
      corroborating reports that herpes-like viruses infect all corals.
      Nucleocytoplasmic large DNA virus (NCLDV) sequences, similar to those recently
      identified in cultures of Symbiodinium (the algal symbionts of corals), were most
      common in bleached corals. This finding further implicates that these NCLDV
      viruses may have a role in bleaching, as suggested in previous studies. This
      study determined that a specific group of viruses is associated with diseased
      Caribbean corals and highlights the potential for viral disease in regional coral
      reef decline. 

PMID- 23949664
TI  - Responses of the coastal bacterial community to viral infection of the algae
      Phaeocystis globosa.
AB  - The release of organic material upon algal cell lyses has a key role in
      structuring bacterial communities and affects the cycling of biolimiting elements
      in the marine environment. Here we show that already before cell lysis the
      leakage or excretion of organic matter by infected yet intact algal cells shaped
      North Sea bacterial community composition and enhanced bacterial substrate
      assimilation. Infected algal cultures of Phaeocystis globosa grown in coastal
      North Sea water contained gamma- and alphaproteobacterial phylotypes that were
      distinct from those in the non-infected control cultures 5 h after infection. The
      gammaproteobacterial population at this time mainly consisted of Alteromonas sp.
      cells that were attached to the infected but still intact host cells. Nano-scale
      secondary-ion mass spectrometry (nanoSIMS) showed ~20% transfer of organic matter
      derived from the infected (13)C- and (15)N-labelled P. globosa cells to
      Alteromonas sp. cells. Subsequent, viral lysis of P. globosa resulted in the
      formation of aggregates that were densely colonised by bacteria. Aggregate
      dissolution was observed after 2 days, which we attribute to bacteriophage
      induced lysis of the attached bacteria. Isotope mass spectrometry analysis showed
      that 40% of the particulate (13)C-organic carbon from the infected P. globosa
      culture was remineralized to dissolved inorganic carbon after 7 days. These
      findings reveal a novel role of viruses in the leakage or excretion of algal
      biomass upon infection, which provides an additional ecological niche for
      specific bacterial populations and potentially redirects carbon availability. 

PMID- 23949666
TI  - Remote monitoring of cardiovascular implantable devices in the pediatric
      population improves detection of adverse events.
AB  - With the exponential growth of cardiovascular implantable electronic devices
      (CIEDs) in pediatric patients, a new method of long-term surveillance, remote
      monitoring (RM), has become the standard of care. The purpose of this study was
      to determine the usefulness of RM as a monitoring tool in the pediatric
      population. A retrospective review was performed of 198 patients at the
      University of Iowa Children's Hospital who had CIEDs. Data transmitted by RM were
      analyzed. The following data were examined: patient demographics; median interval
      between transmissions; detection of adverse events requiring corrective measures,
      including detection of lead failure; detection of arrhythmias and device
      malfunctions independent of symptoms; time gained in the detection of events
      using RM versus standard practice; the validity of RM; and the impact of RM on
      data management. Of 198 patients, 162 submitted 615 RM transmissions. The median
      time between remote transmissions was 91 days. Of 615 total transmissions, 16 %
      had true adverse events with 11 % prompting clinical intervention. Of those
      events requiring clinical response, 61 % of patients reported symptoms. The
      median interval between last follow-up and occurrence of events detected by RM
      was 46 days, representing a gain of 134 days for patients followed-up at 6-month
      intervals and 44 days for patients followed-up at 3 month-intervals. The
      sensitivity and specificity of RM were found to be 99 and 72 %, respectively. The
      positive and negative predictive values were found to be 41 and 99 %,
      respectively. RM allows for early identification of arrhythmias and device
      malfunctions, thus prompting earlier corrective measures and improving care and
      safety in pediatric patients. 

PMID- 23949665
TI  - Two-stage microbial community experimental design.
AB  - Microbial community samples can be efficiently surveyed in high throughput by
      sequencing markers such as the 16S ribosomal RNA gene. Often, a collection of
      samples is then selected for subsequent metagenomic, metabolomic or other follow
      up. Two-stage study design has long been used in ecology but has not yet been
      studied in-depth for high-throughput microbial community investigations. To avoid
      ad hoc sample selection, we developed and validated several purposive sample
      selection methods for two-stage studies (that is, biological criteria) targeting
      differing types of microbial communities. These methods select follow-up samples
      from large community surveys, with criteria including samples typical of the
      initially surveyed population, targeting specific microbial clades or rare
      species, maximizing diversity, representing extreme or deviant communities, or
      identifying communities distinct or discriminating among environment or host
      phenotypes. The accuracies of each sampling technique and their influences on the
      characteristics of the resulting selected microbial community were evaluated
      using both simulated and experimental data. Specifically, all criteria were able
      to identify samples whose properties were accurately retained in 318 paired 16S
      amplicon and whole-community metagenomic (follow-up) samples from the Human
      Microbiome Project. Some selection criteria resulted in follow-up samples that
      were strongly non-representative of the original survey population; diversity
      maximization particularly undersampled community configurations. Only selection
      of intentionally representative samples minimized differences in the selected
      sample set from the original microbial survey. An implementation is provided as
      the microPITA (Microbiomes: Picking Interesting Taxa for Analysis) software for
      two-stage study design of microbial communities. 

PMID- 23949667
TI  - Life cycle of Glyphepomis spinosa Campos & Grazia (Hemiptera: Pentatomidae): a
      new pest of rice in Brazil.
AB  - Nymph and adult biology of Glyphepomis spinosa Campos & Grazia (Hemiptera:
      Pentatomidae) was studied on rice plants under laboratory and greenhouse
      conditions. The full life cycle of G. spinosa lasted 50.1 day. Nymph development
      ranged from 2.7 days for the first instar up to 11.9 days for the fifth instar.
      The egg stage showed the highest per capita rate of mortality (0.16). Nearly 13%
      of all eggs were laid on the same day. The sex ratio was 0.5. The average
      hatching rate was 58.0%. Pre-oviposition, oviposition, and post-oviposition
      periods took 12.9, 34.4, and 6.2 days, respectively. 

PMID- 23949668
TI  - The ecological basis for biogeographic classification: an example in orchid bees
      (Apidae: Euglossini).
AB  - Biogeography has been difficult to apply as a methodological approach because
      organismic biology is incomplete at levels where the process of formulating
      comparisons and analogies is complex. The study of insect biogeography became
      necessary because insects possess numerous evolutionary traits and play an
      important role as pollinators. Among insects, the euglossine bees, or orchid
      bees, attract interest because the study of their biology allows us to explain
      important steps in the evolution of social behavior and many other adaptive
      tradeoffs. We analyzed the distribution of morphological characteristics in
      Colombian orchid bees from an ecological perspective. The aim of this study was
      to observe the distribution of these attributes on a regional basis. Data
      corresponding to Colombian euglossine species were ordered with a correspondence
      analysis and with subsequent hierarchical clustering. Later, and based on
      community proprieties, we compared the resulting hierarchical model with the
      collection localities to seek to identify a biogeographic classification pattern.
      From this analysis, we derived a model that classifies the territory of Colombia
      into 11 biogeographic units or natural clusters. Ecological assumptions in
      concordance with the derived classification levels suggest that species
      characteristics associated with flight performance, nectar uptake, and social
      behavior are the factors that served to produce the current geographical
      structure. 

PMID- 23949669
TI  - Distribution of Chironomidae in a semiarid intermittent river of Brazil.
AB  - The effects of the intermittency of water flow on habitat structure and substrate
      composition have been reported to create a patch dynamics for the aquatic fauna,
      mostly for that associated with the substrate. This study aims to describe the
      spatial distribution of Chironomidae in an intermittent river of semiarid Brazil
      and to associate assemblage composition with environmental variables. Benthic
      invertebrates were sampled during the wet and dry seasons using a D-shaped net
      (40 cm wide and 250 MUm mesh), and the Chironomidae were identified to genus
      level. The most abundant genera were Tanytarsus, Polypedilum, and Saetheria with
      important contributions of the genera Procladius, Aedokritus, and Dicrotendipes.
      Richness and density were not significantly different between the study sites,
      and multiple regression showed that the variation in richness and density
      explained by the environmental variables was significant only for substrate
      composition. The composition of genera showed significant spatial segregation
      across the study sites. Canonical Correspondence Analysis showed significant
      correspondence between Chironomidae composition and the environmental variables,
      with submerged vegetation, elevation, and leaf litter being important predictors
      of the Chironomidae fauna. This study showed that Chironomidae presented
      important spatial variation along the river and that this variation was
      substantially explained by environmental variables associated with the habitat
      structure and river hierarchy. We suggest that the observed spatial segregation
      in the fauna results in the high diversity of this group of organisms in
      intermittent streams. 

PMID- 23949670
TI  - Euptychia boulleti (Le Cerf) n. comb. (Lepidoptera: Nymphalidae: Satyrinae), a
      rare and endangered butterfly from Southeastern Brazil.
AB  - This paper discusses the systematic position of the rare and endangered satyrine
      butterfly Caenoptychia boulleti Le Cerf, the only included species in
      Caenoptychia (type species), based on adult morphology and molecular data. The
      results showed that Caenoptychia Le Cerf belongs to the Euptychia Hubner clade,
      and the genus is synonymized with Euptychia, new synonymy. Euptychia boulleti (Le
      Cerf) is a new combination. The male genitalia of E. boulleti showed at least one
      important synapomorphy with the other species of Euptychia, which is the presence
      of a posterior projection of the tegumen above the uncus. Molecular data
      reinforces the position of Caenoptychia within the genus Euptychia. 

PMID- 23949671
TI  - Two new species of Ectobiidae (Blattaria) collected in the Santa Lucia Biological
      Reserve, Espirito Santo, Brazil.
AB  - This contribution describes and illustrates the male genitalia of two new species
      of Ectobiidae belonging to Pseudophyllodromiinae, Chorisoneura Brunner von
      Wattenwyl, and Blattellinae, Xestoblatta Hebard. Both species were collected in
      the Santa Lucia Biological Reserve in the state of Espirito Santo, Brazil. 

PMID- 23949672
TI  - Taxonomy of Mechanitis (f.) (Lepidoptera: Nymphalidae) from the west Colombian
      Andes: an integrative approach.
AB  - Species identification in the butterfly genus Mechanitis (F.) (Lepidoptera:
      Nymphalidae) becomes difficult when it is based only on wing color patterns, a
      common practice in butterfly taxonomy. Difficulties in Mechanitis taxonomy are
      related to the widespread mimicry and polymorphism among species belonging to
      this genus. Species recognition and inventories of Mechanitis genus in geographic
      areas as the Andean region of Colombia are of particular interest and the use of
      more than one character for taxonomic identification is desirable. In this study,
      we included morphological, ecological, and mitochondrial DNA data to identify the
      occurring species in this region. Species of Mechanitis were studied from
      ecological, morphological, and molecular perspectives considering host plant
      identification, oviposition behavior, and life cycles under laboratory
      conditions. Immature morphology, patterns of wing color, and genital structures
      of adults were also studied. The genetic barcoding region of the cytochrome
      oxidase I mitochondrial gene was sequenced and used to verify the limits between
      species previously defined by the other characters and to validate its usefulness
      for species delimitation in this particular genus. The integrative approach
      combining independent datasets successfully allowed species identification as
      compared to the approach based on a single dataset. Three well-differentiated
      species were found in the studied region, Mechanitis menapis (Hewitson),
      Mechanitis polymnia (Linnaeus), and Mechanitis lysimnia (Fabricius). New valuable
      characters that could improve taxonomic identification in this genus are
      considered. 

PMID- 23949673
TI  - Taxonomic study of the genus Eucriotettix hebard (Orthoptera: Tetrigidea) from
      China.
AB  - The genus Eucriotettix Hebard from China was reviewed and 13 were species
      recorded, including two new species: Eucriotettix nigripennis Deng & Zheng n. sp.
      and Eucriotettix strictivertex Deng & Zheng n. sp. A key to the species of
      Eucriotettix from China is provided. Type specimens were deposited in the
      Institute of Zoology, Shaanxi Normal University. 

PMID- 23949674
TI  - Energy allocation changes in overwintering adults of the common pistachio Psylla,
      Agonoscena pistaciae Burckhardt & Lauterer (Hemiptera: Psyllidae).
AB  - The common pistachio psylla, Agonoscena pistaciae Burckhardt & Lauterer
      (Hemiptera: Psyllidae), is known as the key pest of pistachio orchards in Iran.
      This pest passes the winter as adults. In this study, energy allocation changes
      in relation to ambient temperature were investigated in field-collected adults by
      measuring total body sugar, trehalose, glucose, sorbitol, myoinositol, glycogen,
      lipid, and protein contents. Glycogen content decreased with decrease in ambient
      temperature. The decrease in glycogen content was proportional to the increase in
      total body sugar, trehalose, myoinositol, and sorbitol contents. In January, with
      mean ambient temperature of 5.4 degrees C, glycogen content was at the lowest
      level, whereas total body sugar, trehalose, glucose, and sorbitol were at the
      highest level. Total body sugar, trehalose, myoinositol, and sorbitol contents
      increased as temperature decreased from 22.7 degrees C in October to 5.4 degrees
      C in January. In conclusion, low molecular weight carbohydrates and polyols may
      play a role in winter survival and adaptation to cold of the common pistachio
      psylla by providing the required cryoprotection. Also, overwintering adults of
      the common pistachio psylla may store energy in the form of lipid for later
      utilization during the overwintering. 

PMID- 23949675
TI  - A peculiar new Helina Robineau-Desvoidy (Diptera: Muscidae) from Mexico and
      Panama.
AB  - Helina sinaloensis n. sp. (Diptera: Muscidae) is described and illustrated from
      Mexico and Panama. The new species shows a unique combination of characters and
      can be distinguished from the other species of the genus by the prosternum with
      lateral cilia, pre-alar seta absent, anepimeron bare, katepimeron setulose,
      postalar wall setulose and scutellum with setulae on lateroventral margin. 

PMID- 23949676
TI  - Biochemical analysis of a castor bean leaf extract and its insecticidal effects
      against Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae).
AB  - Plant extracts represent a great source of molecules, with insecticidal activity,
      which are used for pest control in several crop production systems. This work
      aimed to evaluate the toxicity of an aqueous extract of leaves of castor bean
      against larvae of Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae) in
      search for different classes of molecules with insecticidal activities by using
      in vitro assays. The effects of the castor bean leaf extract on the food
      utilization, development, and survival of S. frugiperda larvae was evaluated by
      feeding the larvae an artificial diet supplemented with different concentrations
      of the extract (0%, 1%, 2.5%, 5%, and 10% w/v). The effects observed were dose
      dependent, and the highest concentration evaluated (10% w/v) was the one the most
      affected food utilization by altering the nutritional indices, as well as larval
      weight gain, development time, and survivorship. In vitro assays to detect
      saponins, lectins, and trypsin inhibitors in the castor bean leaf extract were
      performed, but only trypsin inhibitors were detected. No preference for the diet
      source was detected in S. frugiperda by feeding the larvae in choice experiments
      with diets containing different concentrations of the castor bean extract tested.
      The data obtained indicate the existence of a potential molecule in the tested
      extract of castor bean to be used as an alternative insecticide to be integrated
      in the management of S. frugiperda. 

PMID- 23949677
TI  - Insecticidal activity of Piper essential oils from the Amazon against the fire
      ant Solenopsis saevissima (Smith) (Hymenoptera: Formicidae).
AB  - Pepper plants in the genus Piper (Piperales: Piperaceae) are common in the
      Brazilian Amazon and many produce compounds with biological activity against
      insect pests. We evaluated the insecticidal effect of essential oils from Piper
      aduncum, Piper marginatum (chemotypes A and B), Piper divaricatum and Piper
      callosum against workers of the fire ant Solenopsis saevissima (Smith)
      (Hymenoptera: Formicidae), as well as their chemical composition by gas
      chromatography and gas chromatography-mass spectrometry. The lowest median lethal
      concentration (LC50) in 48 h was obtained with the oil of P. aduncum (58.4 mg/L),
      followed by the oils of P. marginatum types A (122.4 mg/L) and B (167.0 mg/L), P.
      divaricatum (301.7 mg/L), and P. callosum (312.6 mg/L). The major chemical
      constituents were dillapiole (64.4%) in the oil of P. aduncum; p-mentha-1(7),8
      diene (39.0%), 3,4-methylenedioxypropiophenone (19.0%), and (E)-beta-ocimene
      (9.8%) in P. marginatum chemotype A and (E)-isoosmorhizole (32.2%), (E)-anethole
      (26.4%), isoosmorhizole (11.2%), and (Z)-anethole (6.0%) in P. marginatum
      chemotype B; methyleugenol (69.2%) and eugenol (16.2%) in P. divaricatum; and
      safrole (69.2%), methyleugenol (8.6%), and beta-pinene (6.2%) in P. callosum.
      These chemical constituents have been previously known to possess insecticidal
      properties. 

PMID- 23949678
TI  - Fruits of Mimosa foliolosa (Fabales: Fabaceae) as sleeping shelter for Megachile
      (Pseudocentron) botucatuna (Hymenoptera: Megachilidae).
AB  - Several plant parts or organs are often used by insects for aggregation and even
      as resting areas. We first report the use of fruits of the legume Mimosa
      foliolosa pachycarpa as a night shelter for Megachile (Pseudocentron) botucana
      Schrottky (Hymenoptera: Megachilidae) in Serra do Cipo, southeastern Brazil. Only
      a single bee was found per fruit, in 86 fruits out of 1,003 fruits opened. The
      present findings augmented the occurrence of the phenomenon among bees, which is
      new to the harsh mountaintop environments in the Brazilian rupestrian fields. 

PMID- 23949679
TI  - Order of inoculation affects the success of co-invading entomopathogenic fungi.
AB  - The effect of order of inoculation of Pandora blunckii and Zoophthora radicans co
      infecting Plutella xylostella (L.) (Lepidoptera: Plutellidae) was investigated.
      After co-inoculation, the proportion of larvae infected by either species was
      greatly reduced compared to when they were inoculated singly. The order of
      inoculation influenced the final outcome; the isolate inoculated last always
      killed more larvae than the isolate inoculated first. 

PMID- 23949680
TI  - First host plant record for Teriocolias zelia andina Forbes (Lepidoptera:
      Pieridae) and evidence for local specialization.
AB  - The shrub Senna birostris var. arequipensis (Fabaceae) is recorded as the first
      host plant for the little known butterfly Teriocolias zelia andina Forbes
      (Lepidoptera: Pieridae) in the occidental slopes of the Andes, northernmost
      Chile. Observations on egg-laying and larva-feeding behavior suggest that this
      butterfly is host specific. 

PMID- 23949681
TI  - Single molecule rotational probing of supercooled liquids.
AB  - Much of the interesting behavior that has been observed in supercooled liquids
      appears to be related to dynamic heterogeneity, the presence of distinct dynamic
      environments - with no apparent underlying structural basis - in these systems.
      To most directly interrogate these environments, proposed to span regions just a
      few nanometers across, molecular length scale probes are required. Single
      molecule fluorescent microscopy was introduced to the field a decade ago and has
      provided strong evidence of dynamic heterogeneity in supercooled systems.
      However, only more recently has the full set of challenges associated with
      interpreting results of these experiments been described. With a fuller
      understanding of these challenges in hand, single molecule measurements can be
      employed to provide a more precise picture of dynamic heterogeneity in
      supercooled liquids and other complex systems. In this tutorial review,
      experimental and data analysis details are presented for the most commonly
      employed single molecule approach to studying supercooled liquids, the
      measurement of rotational dynamics of single molecule probes. Guidance is
      provided in experimental set-up and probe selection, with a focus on choices that
      affect data interpretation and probe sensitivity to dynamic heterogeneity. 

PMID- 23949682
TI  - Sorption of copper(II) and silver(I) by four bacterial exopolysaccharides.
AB  - Metal remediation was studied by the sorption of analytical grade copper Cu(II)
      and silver Ag(I) by four exopolysaccharides (EPS) produced by marine bacteria.
      Colorimetric analysis showed that these EPS were composed of neutral sugars,
      uronic acids (>20 %), acetate, and sulfate (29 %). Metal sorption experiments
      were conducted in batch process. Results showed that the maximum sorption
      capacities calculated according to Langmuir model were 400 mg g(-1) EPS (6.29
      mmol g(-1)) and 333 mg g(-1) EPS (3.09 mmol g(-1)) for Cu(II) and Ag(I),
      respectively. Optimum pH values of Ag(I) sorption were determined as 5.7.
      Experiment results also demonstrated the influence of initial silver
      concentration and EPS concentrations. Microanalyzing coupled with scanning
      electron microscopy demonstrated the presence of metal and morphological changes
      of the EPS by the sorption of metallic cations. The Fourier transform infrared
      spectroscopy analysis indicated possible functional groups (e.g., carboxyl,
      hydroxyl, and sulfate) of EPS involved in the metal sorption processes. These
      results showed that EPS from marine bacteria are very promising for copper and
      silver remediation. Further development in dynamic and continuous process at the
      industrial scale will be established next. 

PMID- 23949683
TI  - Improvement of solvent production from xylose mother liquor by engineering the
      xylose metabolic pathway in Clostridium acetobutylicum EA 2018.
AB  - Xylose mother liquor (XML) is a by-product of xylose production through acid
      hydrolysis from corncobs, which can be used potentially for alternative
      fermentation feedstock. Sixteen Clostridia including 13 wild-type, 1 industrial
      strain, and 2 genetically engineered strains were screened in XML, among which
      the industrial strain Clostridium acetobutylicum EA 2018 showed the highest titer
      of solvents (12.7 g/L) among non-genetic populations, whereas only 40% of the
      xylose was consumed. An engineered strain (2018glcG-TBA) obtained by combination
      of glcG disruption and expression of the D-xylose proton-symporter, D-xylose
      isomerase, and xylulokinase was able to completely utilize glucose and L
      arabinose, and 88% xylose in XML. The 2018glcG-TBA produced total solvents up to
      21 g/L with a 50% enhancement of total solvent yield (0.33 g/g sugar) compared to
      that of EA 2018 (0.21 g/g sugar) in XML. This XML-based acetone-butanol-ethanol
      fermentation using recombinant 2018glcG-TBA was estimated to be economically
      promising for future production of solvents.

PMID- 23949684
TI  - [Primary and secondary tumors of the spine].

PMID- 23949685
TI  - [Diagnostic standards for extradural tumors and metastases of the spinal column].
AB  - Because of the heterogeneous clinical and paraclinical symptoms accompanied by
      the urgent necessity to rapidly find a diagnosis, the differential diagnostic
      delineation of spinal tumors from back pain related to other reasons is a special
      challenge in the orthopedic practice. Employing an algorithm based on anamnesis,
      clinical, radiological and paraclinical examinations, a guideline-related biopsy
      as well as histological processing of the biopsy material, tumor lesions can
      usually be classified regarding entity, dignity and extent. Following this a
      treatment strategy can be defined. Because of the necessity of an
      interdisciplinary approach the diagnostic algorithm should be planned during a
      tumor conference and performed in specialized centers. 

PMID- 23949686
TI  - Spin-triplet excitons in 1,3-diphenyl-7-(fur-2-yl)-1,4-dihydro-1,2,4-benzotriazin
      4-yl.
AB  - 7-(Fur-2-yl)benzotriazinyl 1 is the first example of a hydrazyl radical dimer
      with a thermally accessible triplet state. The triplet exciton (|D| = 0.018 cm(
      1), |E| = 0.001 cm(-1)) was observed by solid-state VT-EPR spectroscopy between 5
      and 140 K. VT crystallography, DFT calculations and magnetic susceptibility
      studies reveal a strong temperature dependence of the intra-dimer exchange
      interaction with J/k ~ -254 + 0.0007T(2).

PMID- 23949687
TI  - Heat shock factor OsHsfB2b negatively regulates drought and salt tolerance in
      rice.
AB  - KEY MESSAGE: Expression of OsHsfB2b was strongly induced by heat, salt, ABA and
      PEG treatments. Drought and salt tolerances were significantly decreased by
      OsHsfB2b overexpression, but were enhanced by RNA interference. ABSTRACT: Plants
      have more than 20 heat shock factors (Hsfs) that were designated class A, B, and
      C. Many members of Class A Hsfs were characterized as activators of
      transcription, but the functional roles of class B and C Hsfs have not been fully
      recognized. OsHsfB2b is a member of class B Hsfs in rice (Oryza sativa).
      Expression of OsHsfB2b was strongly induced by heat, salt, abscisic acid (ABA)
      and polyethylene glycol (PEG) treatments but was almost not affected by cold
      stress. Drought and salt tolerances were significantly decreased in OsHsfB2b
      overexpressing transgenic rice, but were enhanced in the OsHsfB2b-RNAi transgenic
      rice. Under drought stress, the OsHsfB2b-overexpressing transgenic rice exhibited
      increased relative electrical conductivity (REC) and content of malondialdehyde
      (MDA) and decreased proline content compared with the wild type, while the lower
      REC and MDA content and increased proline content were found in the OsHsfB2b-RNAi
      transgenic rice. These results suggest that OsHsfB2b functions as a negative
      regulator in response to drought and salt stresses in rice, with its existing B3
      repression domain (BRD) that might be necessary for the repressive activity. The
      present study revealed the potential value of OsHsfB2b in genetic improvement of
      rice.

PMID- 23949688
TI  - Combined excision, cryotherapy, and intraoperative mitomycin C (EXCRIM) for
      localized intraepithelial and squamous cell carcinoma of the conjunctiva.
AB  - BACKGROUND: To report the results of patients undergoing combined excision,
      cryotherapy, and intraoperative mitomycin-C (EXCRIM) for primary ocular surface
      squamous neoplasia (OSSN) METHODS: A retrospective review of a non-comparative
      interventional case series. Histopathologically confirmed primary localized (less
      than four clock hours) OSSN treated with EXCRIM using adjuvant 0.02 % mitomycin-C
      (MMC) were included in the study. The main outcome measures were recurrence and
      complications related to MMC. RESULTS: The study enrolled 28 eyes of 28 patients
      with OSSN with a median age of 64.5 (range 43 to 84) years. The mean tumor size
      was 6.9 * 4.35 mm. There was corneal involvement in 23 of 28 (82 %). Seven
      patients (21 %) had delayed epithelial healing. Two of eight patients (25 %) with
      squamous cell carcinoma (SCC) had positive lateral margins. There were no
      recurrences over a mean follow-up of 49 months (range 24 to 96). CONCLUSION: The
      excision of OSSN combined with cryotherapy and intraoperative MMC is effective
      with a low recurrence rate. Long-term follow-up yielded favorable results.

PMID- 23949689
TI  - Fatty nodules of the dermis of the upper eyelids: a new entity.

PMID- 23949690
TI  - Aminophylline for bradyasystolic cardiac arrest in adults.
AB  - BACKGROUND: In cardiac ischaemia, the accumulation of adenosine may lead to or
      exacerbate bradyasystole and diminish the effectiveness of catecholamines
      administered during resuscitation. Aminophylline is a competitive adenosine
      antagonist. Case studies suggest that aminophylline may be effective for atropine
      resistant bradyasystolic arrest. OBJECTIVES: To determine the effects of
      aminophylline in the treatment of patients in bradyasystolic cardiac arrest,
      primarily survival to hospital discharge. We also considered survival to
      admission, return of spontaneous circulation, neurological outcomes and adverse
      events. SEARCH METHODS: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL; The Cochrane Library, Issue 4, 2009), MEDLINE, EMBASE, CINAHL,
      LILACS, ClinicalTrials.gov and WHO International Clinical Trials Registry
      Platform. We checked the reference lists of retrieved articles, reviewed
      conference proceedings, contacted experts and searched further using Google. The
      search strategy was updated in March 2012. SELECTION CRITERIA: All randomised
      controlled trials comparing intravenous aminophylline with administered placebo
      in adults with non-traumatic, normothermic bradyasystolic cardiac arrest who were
      treated with standard advanced cardiac life support (ACLS). DATA COLLECTION AND
      ANALYSIS: Two review authors independently reviewed the studies and extracted the
      included data. We contacted study authors when needed. Pooled risk ratio (RR) was
      estimated for each study outcome. Subgroup analysis was predefined according to
      the timing of aminophylline administration. MAIN RESULTS: Five trials are
      included in this analysis, all of which were performed in the prehospital
      setting. The risk of bias was low in four of these studies (n = 1186). The trials
      accumulated 1254 participants. Aminophylline was found to have no effect on
      survival to hospital discharge (RR 0.58, 95% confidence interval (CI) 0.12 to
      2.74) or on secondary survival outcome (survival to hospital admission: RR 0.92,
      95% CI 0.61 to 1.39; return of spontaneous circulation: RR 1.15, 95% CI 0.89 to
      1.49). Survival was rare (6/1254), making data about neurological outcomes and
      adverse events quite limited. The planned subgroup analysis for early
      administration of aminophylline included 37 participants. No one in the subgroup
      survived to hospital discharge. AUTHORS' CONCLUSIONS: The prehospital
      administration of aminophylline in bradyasystolic arrest is not associated with
      improved return of circulation, survival to admission or survival to hospital
      discharge. The benefits of aminophylline administered early in resuscitative
      efforts are not known.

PMID- 23949692
TI  - Pericardial effusions in pulmonary arterial hypertension: characteristics,
      prognosis, and role of drainage.
AB  - BACKGROUND: The presence and size of a pericardial effusion in pulmonary arterial
      hypertension (PAH) and its association with outcome is unclear. METHODS: In this
      single-center cohort study of 577 patients with group 1 PAH seen between January
      1, 1995, and December 31, 2005, all patients underwent transthoracic
      echocardiography and were followed for >= 5 years. Echocardiography-guided
      pericardiocentesis was performed as needed. RESULTS: Pericardial effusions on
      index echocardiography occurred in 150 patients (26%); 128 patients had small and
      22 had moderate-sized or larger effusions. Most of the moderate or greater
      effusions occurred in patients who had connective tissue disease (82%). Mean
      right atrial pressure was 13.4 +/- 4.4 mm Hg (no effusion), 15.1 +/- 4.4 mm Hg
      (small effusion), and 17.0 +/- 4.0 mm Hg (moderate or greater effusion) (P <
      .0001). Median survival for patients with moderate or greater effusion, mild
      effusion, or no effusion was 11.3 months, 42.3 months, and 76.5 months,
      respectively. Four of the 22 patients with moderate or greater pericardial
      effusions eventually required echocardiography-guided pericardiocentesis because
      of clinical and echocardiographic evidence of hemodynamic impact. When drained,
      the effusions were large (858 +/- 469 mL) and generally serous. All
      pericardiocenteses were performed cautiously under echocardiographic guidance by
      a highly experienced echocardiologist, with low immediate morbidity and
      mortality. CONCLUSIONS: Pericardial effusions are relatively common but rarely of
      hemodynamic significance in patients with PAH. However, even modest degrees of
      pericardial fluid are associated with a significant increase in mortality and
      appear to reflect the presence of associated collagen vascular disease and high
      right atrial pressure.

PMID- 23949691
TI  - Plant-mediated RNAi of a gap gene-enhanced tobacco tolerance against the Myzus
      persicae.
AB  - Plant-mediated RNAi has been developed as a powerful weapon in the fight against
      agricultural insect pests. The gap gene hunchback (hb) is of crucial importance
      in insect axial patterning and knockdown of hb is deforming and lethal to the
      next generation. The peach potato aphid, Myzus persicae (Sulzer), has many host
      plants and can be found throughout the world. To investigate the effect of plant
      mediated RNAi on control of this insect, the hb gene in M. persicae was cloned,
      plant RNAi vector was constructed, and transgenic tobacco expressing Mphb dsRNA
      was developed. Transgenic tobacco had a different integration pattern of the
      transgene. Bioassays were performed by applying neonate aphids to homozygous
      transgenic plants in the T2 generation. Results revealed that continuous feeding
      of transgenic diet reduced Mphb mRNA level in the fed aphids and inhibited insect
      reproduction, indicating successful knockdown of the target gene in M. persicae
      by plant-mediated RNAi. 

PMID- 23949693
TI  - A case of percutaneous transluminal renal angioplasty for partial coverage of a
      renal artery by a stent graft after endovascular aneurysm repair.
AB  - An elderly woman was admitted to our hospital for evaluation of an abdominal
      aortic aneurysm (AAA) and we decided to treat her AAA with endovascular aneurysm
      repair. Her renal function became worse after the operation and a renogram
      suggested flow disturbance of her right renal artery. We performed angiography
      and checked her right renal artery using intravascular ultrasound. The ultrasound
      revealed thrombus formation and severe stenosis caused by the stent graft. We
      performed percutaneous transluminal renal angioplasty at the ostium of her right
      renal artery. After this procedure, her renal function rapidly improved.

PMID- 23949694
TI  - Inter-animal radiation as potential heat stressor in lying animals.
AB  - A model for predicting inter-animal radiant heat exchange in shaded animals is
      presented, with emphasis on mature cattle. When a cow's surface temperature is 35
      degrees C, as is common in warmer climates, it loses ~510 Watt m(-2) as radiant
      heat. Net radiant heat balance depends on radiation coming from bodies in the
      vicinity. In the 30  degrees C radiant temperature shaded environment typical of
      warm climates, net radiant loss from a lactating cow is ~60 Watt m(-2), i.e., 30
      % of its ~173 Watt m(-2) heat production. Cows rest for 8-14 h day(-1). The heat
      exchange of a lying cow differs from that of a standing one: the body center is
      low and 20-30 % of its surface contacts a surface of relatively low heat
      conductance. Lying reduces the impact of the surrounding shaded area on heat
      exchange but increases that of heat radiating from neighboring cows. When a cow
      rests adjacent to other cows, with 1.25 m between body centers when in stalls, it
      occupies about 140 degrees  of the horizontal plane of view. Heat emitted from
      the animal's surface reduces the net radiant heat loss of a resting cow by ~30
      Watt m(-2). In contrast, the presence of cows at 5 and 10 m distance, e.g., cows
      resting on straw in loose yard housing, reduces the net radiant heat loss of the
      resting cow by 9 and 5 Watt m(-2), respectively. Radiant heat input increases
      with animal density, which is beneficial in cooler climates, but acts as a
      stressor in warm climates.

PMID- 23949695
TI  - Correlates of sexual risk for HIV among US-born and foreign-born Latino men who
      have sex with men (MSM): an analysis from the Brothers y Hermanos study.
AB  - Little research has been conducted to examine whether correlates of sexual risk
      vary by nativity among Latino men who have sex with men (MSM). We used cross
      sectional data collected from 870 Latino MSM recruited with respondent-driven
      sampling techniques. For each sub-sample (US-born and foreign-born), we assessed
      the association between each of the potential correlates (substance use,
      acculturation, social support, and social discrimination) and sexual risk
      behavior. Illicit drug use was associated with increased odds of sexual risk
      behavior in both US-born (OR = 2.17, 95% CI 1.17-4.03) and foreign-born (OR =
      1.86, 1.14-3.05) subgroups. Multivariate correlates specific to foreign-born men
      included binge drinking (OR = 1.91, 1.17-3.14), 15 years or longer spent in the
      US (OR = 1.79, 1.06-3.03) and exposure to social discrimination (OR = 2.02, 1.03
      3.99). Given the diversity of Latino MSM, information from research that
      identifies both common and different HIV risk factors across subgroups of Latino
      MSM may help better tailor HIV prevention programs.

PMID- 23949696
TI  - Flexible Biomanufacturing Processes that Address the Needs of the Future.
AB  - : As the age of the blockbuster drug recedes, the business model for the
      biopharmaceutical industry is evolving at an ever-increasing pace. The
      personalization of medicine, the emergence of biosimilars and biobetters, and the
      need to provide vaccines globally are just some of the factors forcing
      biomanufacturers to rethink how future manufacturing capability is implemented.
      One thing is clear: the traditional manufacturing strategy of constructing large
      scale, purpose-built, capital-intensive facilities will no longer meet the
      industry's emerging production and economic requirements. Therefore, the authors
      of this chapter describe the new approach for designing and implementing flexible
      production processes for monoclonal antibodies and focus on the points to
      consider as well as the lessons learned from past experience in engineering such
      systems. A conceptual integrated design is presented that can be used as a
      blueprint for next-generation biomanufacturing facilities. In addition, this
      chapter discusses the benefits of the new approach with respect to flexibility,
      cost, and schedule. The concept presented here can be applied to other
      biopharmaceutical manufacturing processes and facilities, including-but not
      limited to-vaccine manufacturing, multiproduct and/or multiprocess capability,
      clinical manufacturing, and so on. 

PMID- 23949697
TI  - Transcriptomics as a tool for assessing the scalability of mammalian cell
      perfusion systems.
AB  - DNA microarray-based transcriptomics have been used to determine the time course
      of laboratory and manufacturing-scale perfusion bioreactors in an attempt to
      characterize cell physiological state at these two bioreactor scales. Given the
      limited availability of genomic data for baby hamster kidney (BHK) cells, a
      Chinese hamster ovary (CHO)-based microarray was used following a feasibility
      assessment of cross-species hybridization. A heat shock experiment was performed
      using both BHK and CHO cells and resulting DNA microarray data were analyzed
      using a filtering criteria of perfect match (PM)/single base mismatch (MM) > 1.5
      and PM-MM > 50 to exclude probes with low specificity or sensitivity for cross
      species hybridizations. For BHK cells, 8910 probe sets (39 %) passed the cutoff
      criteria, whereas 12,961 probe sets (56 %) passed the cutoff criteria for CHO
      cells. Yet, the data from BHK cells allowed distinct clustering of heat shock and
      control samples as well as identification of biologically relevant genes as being
      differentially expressed, indicating the utility of cross-species hybridization.
      Subsequently, DNA microarray analysis was performed on time course samples from
      laboratory- and manufacturing-scale perfusion bioreactors that were operated
      under the same conditions. A majority of the variability (37 %) was associated
      with the first principal component (PC-1). Although PC-1 changed monotonically
      with culture duration, the trends were very similar in both the laboratory and
      manufacturing-scale bioreactors. Therefore, despite time-related changes to the
      cell physiological state, transcriptomic fingerprints were similar across the two
      bioreactor scales at any given instance in culture. Multiple genes were
      identified with time-course expression profiles that were very highly correlated
      (> 0.9) with bioprocess variables of interest. Although the current incomplete
      annotation limits the biological interpretation of these observations, their full
      potential may be realized in due course when richer genomic data become
      available. By taking a pragmatic approach of transcriptome fingerprinting, we
      have demonstrated the utility of systems biology to support the comparability of
      laboratory and manufacturing-scale perfusion systems. Scale-down model
      qualification is the first step in process characterization and hence is an
      integral component of robust regulatory filings. Augmenting the current paradigm,
      which relies primarily on cell culture and product quality information, with gene
      expression data can help make a substantially stronger case for similarity. With
      continued advances in systems biology approaches, we expect them to be seamlessly
      integrated into bioprocess development, which can translate into more robust and
      high yielding processes that can ultimately reduce cost of care for patients.

PMID- 23949700
TI  - Heavy metal contamination in tailings and rocksamples from an abandoned
      goldminein Southwestern Nigeria.
AB  - Active and abandoned primary and secondary goldmines have been observed to be
      major sources of metals into the environment. This study assessed the level of
      metal concentrations in rock and tailing samples collected from the abandoned
      primary goldmine site at Iperindo. A total of five rock and ten tailing samples
      were collected for this study. The tailing samples were subjected to
      physicochemical analysis using standard methods. The samples were analyzed for
      metals using inductively coupled plasma/optical emission spectrometry technique.
      The results obtained indicated that tailings were acidic (pH 5.02), with
      electrical conductivity 133.4 MUS/cm, cation exchange capacity 8.95 meq/100 g,
      available phosphorus was 4.74 mg/L, organic carbon 5.58 %, and organic matter
      9.63 %. The trends for metal concentrations within the samples were in the order:
      Zn > Cu > Co > Pb > Cr > As > Cd for rock samples, Cu > Zn > Cr > Pb > As > Co >
      Cd in tailing samples. Cd, Pb, and Zn in the rock were above the Abundance of
      Elements in Average Crustal Rocks standards. Principal component analysis showed
      higher variations among samples in Iperindo. Cd, Pb, Cr, Co, Cu, As, and Zn were
      strongly loaded to principal component 1, with these metals significantly
      contributing to variations in 65.76 % of rock and 53.24 % of tailing. This study
      suggests that the metal concentration in tailings is a reflection of the metal
      composition of the rocks. 

PMID- 23949698
TI  - When less is more: like humans, chimpanzees (Pan troglodytes) misperceive food
      amounts based on plate size.
AB  - We investigated whether chimpanzees (Pan troglodytes) misperceived food portion
      sizes depending upon the context in which they were presented, something that
      often affects how much humans serve themselves and subsequently consume.
      Chimpanzees judged same-sized and smaller food portions to be larger in amount
      when presented on a small plate compared to an equal or larger food portion
      presented on a large plate and did so despite clearly being able to tell the
      difference in portions when plate size was identical. These results are
      consistent with data from the human literature in which people misperceive food
      portion sizes as a function of plate size. This misperception is attributed to
      the Delboeuf illusion which occurs when the size of a central item is
      misperceived on the basis of its surrounding context. These results demonstrate a
      cross-species shared visual misperception of portion size that affects choice
      behavior, here in a nonhuman species for which there is little experience with
      tests that involve choosing between food amounts on dinnerware. The biases
      resulting in this form of misperception of food portions appear to have a deep
      rooted evolutionary history which we share with, at minimum, our closest living
      nonhuman relative, the chimpanzee. 

PMID- 23949699
TI  - Interrelation of 31P-MRS metabolism measurements in resting and exercised
      quadriceps muscle of overweight-to-obese sedentary individuals.
AB  - Phosphorus magnetic resonance spectroscopy ((31)P-MRS) enables the non-invasive
      evaluation of muscle metabolism. Resting Pi-to-ATP flux can be assessed through
      magnetization transfer (MT) techniques, and maximal oxidative flux (Q(max)) can
      be calculated by monitoring of phosphocreatine (PCr) recovery after exercise. In
      this study, the muscle metabolism parameters of 13 overweight-to-obese sedentary
      individuals were measured with both MT and dynamic PCr recovery measurements, and
      the interrelation between these measurements was investigated. In the dynamic
      experiments, knee extensions were performed at a workload of 30% of maximal
      voluntary capacity, and the consecutive PCr recovery was measured in a quadriceps
      muscle with a time resolution of 2 s with non-localized (31)P-MRS at 3 T. Resting
      skeletal muscle metabolism was assessed through MT measurements of the same
      muscle group at 7 T. Significant linear correlations between the Q(max) and the
      MT parameters k(ATP) (r = 0.77, P = 0.002) and F(ATP) (r = 0.62, P = 0.023) were
      found in the study population. This would imply that the MT technique can
      possibly be used as an alternative method to assess muscle metabolism when
      necessary (e.g. in individuals after stroke or in uncooperative patients).

PMID- 23949701
TI  - An increased alveolar CD4 + CD25 + Foxp3 + T-regulatory cell ratio in acute
      respiratory distress syndrome is associated with increased 30-day mortality.
AB  - PURPOSE: Cell therapy may become an option for lung injury treatment. However, no
      data are available on the alveolar presence and time course of CD4+ CD25 + Foxp3
      + T-regulatory lymphocyte cells (Tregs) in acute respiratory distress syndrome
      (ARDS). Accordingly, we (1) measured the ratio of CD4 + CD25 + Foxp3 + Tregs to
      all (CD4+) lymphocytes in the bronchoalveolar lavage (BAL) of ARDS patients and
      of control subjects without lung disease and (2) assessed their impact on 30-day
      mortality. METHODS: In a prospective study, the ratios of CD4 + CD25 + Foxp3 + T
      regulatory cells to all CD4+ cells were measured (FACS) within 24 h of the
      patients' ICU referral in the BAL and in the blood of 47 patients with ARDS (32
      males, 15 females; mean age 44 years +/-13) as well as in 8 controls undergoing
      elective abdominal surgery (5 men, 3 women; mean age 49 years +/-4). BAL
      concentrations of several cytokines were also measured in ARDS patients. RESULTS:
      Tregs were detected in the BAL of control subjects and ARDS patients. However,
      the mean ratio of Tregs to all CD4+ lymphocytes was threefold greater in ARDS non
      survivors (16.5%; p = 0.025) and almost twofold greater in ARDS survivors (9.0%;
      p = 0.015) compared to controls (5.9%). Multivariate Cox regression analysis
      revealed the ratio of CD4 + CD25 + Foxp3 + T-regulatory lymphocytes to all CD4+
      lymphocytes in the BAL to be an important and independent prognostic factor for
      30-day survival (HR 6.5; 95% CI, 1.7-25; p = 0.006). CONCLUSION: An increased T
      regulatory cell ratio in the admission BAL of patients with ARDS is an important
      and independent risk factor for 30-day mortality.

PMID- 23949702
TI  - Nutrition support during extracorporeal membrane oxygenation (ECMO) in adults: a
      retrospective audit of 86 patients.
AB  - PURPOSE: Extracorporeal membrane oxygenation (ECMO) is increasingly being used to
      support critically ill patients with severe cardiac and/or respiratory failure.
      It has been claimed that the resulting haemodynamic alterations, particularly in
      venoarterial ECMO, mean that enteral feeding is unsafe and/or poorly tolerated.
      This study aims to investigate this question and to identify any barriers to
      optimal nutrition. METHODS: Data were retrospectively collected for 86 patients
      who received ECMO between January 2007 and July 2012 in a tertiary critical care
      unit/ECMO referral centre. All were fed using existing protocols that emphasise
      early enteral feeding in preference over parenteral or delayed enteral nutrition.
      RESULTS: Thirty-one patients required ECMO for cardiac failure, and all of these
      received venoarterial ECMO; the remainder received venovenous ECMO. Enteral feeds
      started for all patients at average 13.1 h [standard deviation (SD) 16.7 h] after
      ICU admission, reaching goal rate on day 2.6 (SD 1.4). Thirty-three patients
      experienced significant feeding intolerance during the first 5 days, but of these
      20 were managed effectively with prokinetic medications; 18 required parenteral
      nutrition to supplement inadequately tolerated tube feeds. Intolerance did not
      differ between ECMO modes. Overall patients tolerated 79.7% of goal nutrition
      each day in the first 2 weeks. CONCLUSIONS: Enteral feeding can be well tolerated
      by patients who are receiving ECMO, whether in venovenous or venoarterial mode.
      ECMO should not exclude patients from receiving the well-documented benefits of
      early enteral feeding in critical illness.

PMID- 23949703
TI  - Hospital mortality prognostication in sepsis using the new biomarkers suPAR and
      proADM in a single determination on ICU admission.
AB  - PURPOSE: The soluble form of the urokinase-type plasminogen activator receptor
      (suPAR) and proadrenomedullin (proADM) are two new and promising sepsis
      biomarkers. We assessed the prognostic value of a single determination of proADM
      and suPAR, comparing them with C-reactive protein (CRP) and procalcitonin (PCT),
      and evaluating whether their addition to severity scores (APACHE II and SOFA)
      could improve their prognostic accuracy. METHODS: A single-centre prospective
      observational study conducted in an adult intensive care department at Marques de
      Valdecilla University Hospital in Spain. APACHE II and SOFA scores, CRP, PCT,
      suPAR and proADM levels on the day of ICU admission were collected. RESULTS: A
      total of 137 consecutive septic patients were studied. The best area under the
      curve (AUC) for the prediction of in-hospital mortality was for APACHE II (0.82)
      and SOFA (0.75) scores. The ROC curve for suPAR yielded an AUC of 0.67, higher
      than proADM (0.62), CRP (0.50) and PCT (0.44). Significant dose-response trends
      were found between hospital mortality and suPAR (OR Q4 = 4.83, 95% CI 1.60-14.62)
      and pro-ADM (OR Q4 = 3.00, 95% CI 1.06-8.46) quartiles. Non-significant
      associations were found for PCT and CRP. The combination of severity scores and
      each biomarker did not provide superior AUCs. CONCLUSIONS: SuPAR and, to a lesser
      extent, proADM levels on ICU admission were better tools in prognosticating in
      hospital mortality than CRP or PCT. However, neither of the two new biomarkers
      has been demonstrated to be excessively useful in the current setting. The
      prognostic accuracy was better for severity scores than for any of the
      biomarkers.

PMID- 23949704
TI  - An urgent plea: give the use of prolonged propofol infusion a second thought.

PMID- 23949706
TI  - An unexpected aortic valve in trisomy 21.

PMID- 23949705
TI  - NGAL and AKI: the end of a myth?

PMID- 23949707
TI  - Exchange of natural enemies for biological control: is it a rocky road?-the road
      in the Euro-Mediterranean region and the South American common market.
AB  - The access and benefit sharing (ABS) regulations from the Convention on
      Biological Diversity (CBD) for the use of natural resources became an important
      issue because the biodiversity of developing countries was heavily accessed and
      unilaterally exploited by pharmaceutical and seed companies. However, natural
      enemies used for biological control are living and unmodified genetic resources
      which cannot be patented and have been treated as resources such as drugs, seeds,
      or other commercial products. Consequently, the ABS requirements have limited not
      only the use of natural enemies but also the positive effects that scientifically
      supported biological control strategies have on the society, the environment, and
      the economy, reducing problems of pesticide residues, water and soil
      contamination, and non-target effects. During the last several years, the
      biological control scientific community has faced new and extremely complicated
      legislation dictated by a high and diverse number of governmental agencies at
      different levels, making the access to natural resources for biocontrol purposes
      a rocky road. Society at large should be aware of how the strict ABS regulations
      affect the use of natural enemies as biological resources to secure food
      production, food safety, and global environmental protection. We discuss in here
      the current difficulties derived from CBD for the exchange of natural enemies
      taking as example the Euro-Mediterranean region, Argentina, and Brazil to
      demonstrate how long and diverse are the steps to be followed to obtain the
      required permits for access and exportation/importation of natural enemies. We
      then argue that the public visibility of biocontrol strategies should be
      increased and their benefits highlighted in order to persuade legislators for the
      development of a less bureaucratic, more expedient, and more centralized
      regulatory frame, greatly favoring the practice and benefits of biological
      control. We finally propose a general framework in which ABS issues should be
      dealt in ways to attend the CBD, but also to make the use of natural resources
      for the biological control of pests to secure food production and security a
      possible alternative. 

PMID- 23949708
TI  - Composition and structure of the Chironomidae (Insecta: Diptera) community
      associated with bryophytes in a first-order stream in the Atlantic forest,
      Brazil.
AB  - This study describes the structure of the Chironomidae community associated with
      bryophytes in a first-order stream located in a biological reserve of the
      Atlantic Forest, during two seasons. Samples of bryophytes adhered to rocks along
      a 100-m stretch of the stream were removed with a metal blade, and 200-mL pots
      were filled with the samples. The numerical density (individuals per gram of dry
      weight), Shannon's diversity index, Pielou's evenness index, the dominance index
      (DI), and estimated richness were calculated for each collection period (dry and
      rainy). Linear regression analysis was employed to test the existence of a
      correlation between rainfall and the individual's density and richness. The high
      numerical density and richness of Chironomidae taxa observed are probably related
      to the peculiar conditions of the bryophyte habitat. The retention of larvae
      during periods of higher rainfall contributed to the high density and richness of
      Chironomidae larvae. The rarefaction analysis showed higher richness in the rainy
      season related to the greater retention of food particles. The data from this
      study show that bryophytes provide stable habitats for the colonization by and
      refuge of Chironomidae larvae, mainly under conductions of faster water flow and
      higher precipitation. 

PMID- 23949709
TI  - Aquatic insect assemblages of man-made permanent ponds, Buenos Aires city,
      Argentina.
AB  - Freshwater habitats are important elements within urban green space and they are
      endangered by various types of human activity. With the aim to increase the
      knowledge about species biodiversity in urban ecosystems, we characterised the
      assemblages of aquatic insects in four permanent man-made ponds in Buenos Aires
      city (Argentina) during a 1-year period. We recorded 32 species with Sigara spp.
      (Hemiptera) as the most abundant. The removal of aquatic vegetation from the
      studied ponds may have affected both the establishment and permanence of the
      insect community. Swimmers were the dominant group in the studied sites, followed
      by burrowers and sprawlers, and only a few strictly climbers were collected.
      Therefore, all sampled ponds were dominated by collectors (principally
      gatherers), secondarily by predators and only few shredders were detected, which
      was much affected by the removal of macrophytes. Non-parametric abundance indexes
      estimated a number of species very close to the observed number in each site.
      Conversely, the incidence indexes estimated more species because there were many
      more taxa present only in one sample than those represented by few individual in
      a sample. Our data provides some insights on the community of man-made ponds that
      can improve the management of these aquatic urban habitats. Considering that
      macrophytes affect animal assemblages due to their role as physical structures
      that increase the complexity or heterogeneity of habitats, they should not be
      removed by authorities in order to promote biodiversity. 

PMID- 23949710
TI  - Loss of genetic variability induced by Agroecosystems: Chrysoperla externa
      (Hagen) (Neuroptera: Chrysopidae) as a case study.
AB  - Four species of green lacewings occur in Brazil, of which Chrysoperla externa
      (Hagen) (Neuroptera: Chrysopidae) exhibits the widest geographical distribution.
      Chrysoperla externa is a predatory insect that is potentially useful as a
      biological control agent of agricultural pests. Studies on the genetic diversity
      of lacewing populations are essential to reduce the environmental and economic
      harm that may be caused by organisms with a low ability to adapt to the adverse
      and/or different environmental conditions to which they are exposed. We used the
      cytochrome oxidase I mitochondrial gene as a molecular marker to investigate the
      genetic diversity of green lacewing species collected from native and
      agroecosystem environments. Populations derived from native areas showed higher
      rates of genetic variability compared to populations from agroecosystems.
      Demographic changes in the form of population expansion were observed in
      agroecosystems, whereas populations in the native environment appeared stable
      over time. A statistical analysis showed significant genetic structure between
      each of the sampled groups, combined with its complete absence within each group,
      corroborating each group's identity. We infer that the loss of variability
      exhibited by populations from the agroecosystems is the result of genetic drift
      by means of the founder effect, a similar effect that has been observed in other
      introduced populations. Agroecosystems might therefore function as exotic areas
      for green lacewings, even when these areas are within the normal range of the
      species. 

PMID- 23949711
TI  - Review of Mexican species of Podogaster Brulle (Hymenoptera: Ichneumonidae:
      Anomaloninae) with description of two new species.
AB  - Two new species of Podogaster Brulle, Podogaster brunneus n. sp. and Podogaster
      lagartensis n. sp., are described. The material was collected with Malaise traps
      operated for a year in the Ria Lagartos Biosphere Reserve, a dry tropical area of
      Southeast Mexico. Podogaster rosteri Gauld & Bradshaw is synonymized with
      Podogaster mexicanus (Cresson). A key to the Mexican species is also provided. 

PMID- 23949712
TI  - Two new species of Anastrepha Schiner (Diptera, Tephritidae) closely related to
      Anastrepha pickeli Lima.
AB  - Anastrepha entodonta n. sp. and Anastrepha hadropickeli n. sp. are described and
      illustrated. The new species belong to the spatulata group. Both species occur
      sympatrically with Anastrepha pickeli Lima in the semiarid region of the state of
      Minas Gerais, Brazil. Anastrepha hadropickeli occurs also in the semiarid of the
      state of Rio Grande do Norte, Brazil, where it was misidentified as A. pickeli. 

PMID- 23949713
TI  - Description of the male of Laneella perisi (Mariluis) (Diptera: Calliphoridae) n.
      comb.
AB  - The male Laneella perisi (Mariluis) n. comb. is described based on specimens
      collected in the Cordillera Oriental (1,370-1,450 m asl), Florencia-Suaza,
      Caqueta, Colombia. A key to separate the two species of the genus Laneella and
      illustrations of the male genitalia and female abdomen, terminalia, and
      spermatheca are also presented. 

PMID- 23949714
TI  - Description of a new genus and three new species of Figitinae (Hymenoptera:
      Cynipoidea: Figitidae) from Colombia.
AB  - A new genus and three new species of Figitinae (Hymenoptera: Figitidae) are
      described from Colombia: Ferpereira Pujade-Villar n. gen., Ferpereira fiorellae
      Pujade-Villar n. sp., Neralsia levis Pujade-Villar & Petersen-Silva n. sp., and
      Figites colombiensis Pujade-Villar & Paretas-Martinez n. sp., which is the first
      species of Figites Latreille from Colombia and the second from South America. The
      diagnostic characters of these new taxa are illustrated. 

PMID- 23949715
TI  - Spatial and temporal variation in Chaetanaphothrips orchidii Moulton
      (Thysanoptera: Thripidae) population and its damage on lemon.
AB  - Chaetanaphothrips orchidii Moulton has recently been detected in lemon (Citrus
      limon) orchards in northwest Argentina, causing high levels of damage on fruits.
      Severe damage results in the rejection of fruit for export, which must then be
      sold in the industry. However, the restrictions imposed by the citrus industry on
      insecticide residues sometimes also result in fruit rejection. Here, we studied
      the ecology and behavior of C. orchidii in order to propose a pest management
      strategy that could meet both export and industry demands. Seasonal occurrence
      and canopy distribution of C. orchidii in lemon orchards were evaluated, and
      field experimental manipulations of thrips populations were performed to analyze
      how the length (45, 100, 130, and 200 days) and timing (January, February, or
      March) of C. orchidii activity related with fruit damage. Lemons harvested during
      summer showed lower infestation levels (~0.64 individual per fruit) than those
      harvested in winter (~1.88 individuals per fruit). Higher proportions of damaged
      fruits were recorded in the lower part of the tree. Changes in the population
      levels of C. orchidii were closely associated with fruit phenology. The longer
      the lemon fruits were exposed to the thrips, the higher was the damage. However,
      the time of infestations did not affect fruit damage. Our data provide a first
      step towards understanding the factors that determine the severity of fruit
      damage caused by C. orchidii in northwest Argentina. 

PMID- 23949716
TI  - Evaluation of the Boll Weevil Anthonomus grandis Boheman (Coleoptera:
      Curculionidae) suppression program in the state of Goias, Brazil.
AB  - The boll weevil Anthonomus grandis Boheman (Coleoptera: Curculionidae) is the
      most important cotton pest in Brazil. A large-scale field-testing of a Boll
      Weevil Suppression Program (BWSP) was implemented to assess its technical and
      operational feasibility for boll weevil suppression in the state of Goias,
      Brazil. The pilot plan focused on 3,608 ha of cotton during the 2006/2007 and
      6,011 ha in the 2007/2008 growing seasons; the areas were divided into four inner
      zones with an outer buffer zone. We analyzed data on boll weevil captures using
      pheromone traps installed in the BWSP fields, on the detection of the first
      insect and the first damaged floral bud, greatest damage, and number of
      insecticide applications. The nonparametric Mann-Whitney U test was used to
      evaluate the differences between presuppression and suppression years. Fourteen
      pheromone-baited trapping evaluations were used to compare the weevil populations
      from 2006/2007 and 2007/2008 growing seasons. The BWSP regime reduced in-season
      boll weevil captures from 15- to 500-fold compared to presuppression levels in
      the preceding year. The low capture rates were related to delays in infestation
      and damage by weevils. The smaller population size measured by trapping and field
      monitoring reduced the number of required insecticide treatments. The BWSP
      strategy was efficient in suppressing populations of this pest and is a viable
      program for cotton production in subtropical and tropical regions, with long-term
      economic and environmental benefits. 

PMID- 23949717
TI  - Insecticidal and repellent activities of the essential oil of Callistemon
      citrinus (Myrtaceae) against Callosobruchus maculatus (F.) (Coleoptera:
      Bruchidae).
AB  - The essential oil of Callistemon citrinus (Curtis) leaves was extracted by hydro
      distillation and tested on female and male adults of Callosobruchus macullatus
      (F.) for insecticidal and repellent effects. GC-MS analysis was used to identify
      and quantify the volatile composition of the essential oil. Results showed that
      1,8-cineole (34.2%) and alpha-pinene (29.0%) were the major components of the
      oil. Callistemon citrinus oil was found to be toxic to adult insects when applied
      by fumigation. Responses varied according to the gender of the insect and
      exposure time. LC50 values were 12.88 and 84.4 MUL. L(-1) for males and females,
      respectively. An increase in exposure time from 3 to 24 h caused an increase in
      mortality from 50% to 100% in males and from 15.5% to 85.2% in females, at the
      highest concentration (500 MUL. L(-1)). The essential oil also had a repellent
      effect against C. macullatus in a filter paper arena test. After 2 and 4 h, 86%
      and 94%, respectively, repellent effects were demonstrated at the highest
      concentration of 0.4 MUL .cm(-2). These observations suggest that C. citrinus
      essential oil may be usefully applied to control storage pests. 

PMID- 23949718
TI  - Population fluctuation and damage caused by phytophagous mites on three rubber
      tree clones.
AB  - Our aim was to investigate the population fluctuation and the damage caused by
      the phytophagous mites Calacarus heveae Feres, Tenuipalpus heveae Baker, and
      Eutetranychus banksi (McGregor) on clones FX 2784, FX 3864, and MDF 180 in rubber
      tree crops from southeastern Bahia, Brazil. Moreover, we tested for the influence
      of climatic variables on occurrence patterns of these species throughout weekly
      samples performed from October to April. The infestation peaks was between mid
      January and late February. The clones FX 2784 and FX 3864 had the highest
      infestations and more severe damage possibly caused by C. heveae, which was the
      most frequent and abundant species in all clones. We found that sunlight duration
      and rainfall were the most important factors for C. heveae while T. heveae was
      affected by rainfall and temperature. Eutetranychus banksi was only affected by
      sunlight duration. However, the best models had low goodness of fit. We concluded
      that the clones FX 2784 and FX 3864 had a higher susceptibility to mite attack,
      and the association between climatic variables and favorable physiological
      conditions were determinant for the population increase of the species from
      January to April. 

PMID- 23949719
TI  - Field evaluation of Bt cotton crop impact on nontarget pests: cotton aphid and
      boll weevil.
AB  - Bt cotton plants expressing Cry1Ac protein have high specificity for the control
      of lepidopteran larvae. However, studies conducted in several countries have
      shown these plants have a differential impact on nontarget herbivores. The aim of
      this study was to compare the colonization rates and population abundance of the
      cotton aphid, Aphis gossypii Glover (Hemiptera: Aphididae) and the boll weevil,
      Anthonomus grandis Boheman (Coleoptera: Curculionidae), in plots of Bt (Nuopal)
      and non-Bt cotton (Delta Opal) in an experimental field in Brasilia, DF, Brazil.
      No difference was observed in the preference and colonization by winged aphids to
      plants from the two treatments. There was no significant difference in abundance
      of wingless aphids or in the production of winged aphids between treatments.
      Apparently, the parameters that control factors such as fecundity, survival, and
      dispersal were similar on both Bt and non-Bt plants. Monitoring of plants for
      coccinellids, a specialist predator of aphids, and ants that act on the dispersal
      of aphids among plants showed no significant difference between Bt and non-Bt
      plants, supporting the inference above. Regarding the effect on boll weevil,
      there was also no significant difference between treatments in the total number
      of fruiting structures attacked in each plot, the percentage of fruiting
      structures attacked per plant or on the number of weevils emerging from fruits
      with boll weevil damage from egg-laying, when damaged fruit samples were held in
      the laboratory. Based on these results, we conclude that there is no impact of Bt
      cotton crop expressing Cry1Ac on the nontarget herbivores tested under field
      conditions. 

PMID- 23949720
TI  - First record of Acrocercops serrigera serrigera Meyrick (Lepidoptera:
      Gracillariidae) from Chile.
AB  - Acrocercops Wallengren (Gracillariidae) is recorded for the first time from
      Chile. The little known Acrocercops serrigera serrigera Meyrick is reported from
      the Azapa Valley, Arica Province, northern Chilean coastal desert. Specimens were
      reared from Malva nicaeensis and Waltheria ovata (both Malvaceae). Specimen
      identification is based on comparisons of the male genitalia with that of the
      lectotype of the species originated from Peru. Sequences of a fragment of the
      mitochondrial gene cytochrome oxidase subunit I of specimens reared on both
      plants indicate that there is only one Acrocercops species involved as only one
      substitution site was found over the 524-bp sequenced. 

PMID- 23949721
TI  - First record of Elixothrips brevisetis (Bagnall) (Thysanoptera: Thripidae) in
      Brazil.
AB  - Elixothrips brevisetis (Bagnall), a species exotic to Brazil, is first recorded
      in the country. Individuals were collected on banana fruits (Musa sp.) (Musaceae)
      in July 2010 in the municipality of Luis Alves, state of Santa Catarina, causing
      rusting on the fruit peel in several bunches of bananas. 

PMID- 23949723
TI  - Highly diastereoselective synthesis of chiral aminophenolate zinc complexes and
      isoselective polymerization of rac-lactide.
AB  - An enantiopure zinc complex supported by an aminophenolate ligand with multiple
      stereogenic centers has been diastereoselectively synthesized via the variation
      of the ortho-substituent of a phenoxy moiety and the N-alkyl group of a chiral
      pyrrolidinyl ring in the ligand framework, which displays high isoselectivity in
      the polymerization of rac-lactide. 

PMID- 23949722
TI  - Hypothalamic-pituitary-thyroid axis hormones stimulate mitochondrial function and
      biogenesis in human hair follicles.
AB  - Thyroid hormones regulate mitochondrial function. As other hypothalamic-pituitary
      thyroid (HPT) axis hormones, i.e., thyrotropin-releasing hormone (TRH) and
      thyrotropin (TSH), are expressed in human hair follicles (HFs) and regulate
      mitochondrial function in human epidermis, we investigated in organ-cultured
      human scalp HFs whether TRH (30 nM), TSH (10 mU ml(-1)), thyroxine (T4) (100 nM),
      and triiodothyronine (T3) (100 pM) alter intrafollicular mitochondrial energy
      metabolism. All HPT-axis members increased gene and protein expression of
      mitochondrial-encoded subunit 1 of cytochrome c oxidase (MTCO1), a subunit of
      respiratory chain complex IV, mitochondrial transcription factor A (TFAM), and
      Porin. All hormones also stimulated intrafollicular complex I/IV activity and
      mitochondrial biogenesis. The TSH effects on MTCO1, TFAM, and porin could be
      abolished by K1-70, a TSH-receptor antagonist, suggesting a TSH receptor-mediated
      action. Notably, as measured by calorimetry, T3 and TSH increased follicular heat
      production, whereas T3/T4 and TRH stimulated ATP production in cultured HF
      keratinocytes. HPT-axis hormones did not increase reactive oxygen species (ROS)
      production. Rather, T3 and T4 reduced ROS formation, and all tested HPT-axis
      hormones increased the transcription of ROS scavengers (catalase, superoxide
      dismutase 2) in HF keratinocytes. Thus, mitochondrial biology, energy metabolism,
      and redox state of human HFs are subject to profound (neuro-)endocrine regulation
      by HPT-axis hormones. The neuroendocrine control of mitochondrial biology in a
      complex human mini-organ revealed here may be therapeutically exploitable.

PMID- 23949724
TI  - Medical students' emotional development in early clinical experience: a model.
AB  - Dealing with emotions is a critical feature of professional behaviour. There are
      no comprehensive theoretical models, however, explaining how medical students
      learn about emotions. We aimed to explore factors affecting their emotions and
      how they learn to deal with emotions in themselves and others. During a first
      year nursing attachment in hospitals and nursing homes, students wrote daily
      about their most impressive experiences, explicitly reporting what they felt,
      thought, and did. In a subsequent interview, they discussed those experiences in
      greater detail. Following a grounded theory approach, we conducted a constant
      comparative analysis, collecting and then interpreting data, and allowing the
      interpretation to inform subsequent data collection. Impressive experiences set
      up tensions, which gave rise to strong emotions. We identified four 'axes' along
      which tensions were experienced: 'idealism versus reality', 'critical distance
      versus adaptation', 'involvement versus detachment' and 'feeling versus
      displaying'. We found many factors, which influenced how respondents relieved
      those tensions. Their personal attributes and social relationships both inside
      and outside the medical community were important ones. Respondents' positions
      along the different dimensions, as determined by the balance between attributes
      and tensions, shaped their learning outcomes. Medical students' emotional
      development occurs through active participation in medical practice and having
      impressive experiences within relationships with patients and others on wards.
      Tensions along four dimensions give rise to strong emotions. Gaining insight into
      the many conditions that influence students' learning about emotions might
      support educators and supervisors in fostering medical students' emotional and
      professional development. 

PMID- 23949725
TI  - Image noise-based dose adaptation in dynamic volume CT of the heart: dose and
      image quality optimisation in comparison with BMI-based dose adaptation.
AB  - OBJECTIVES: To compare the image quality and radiation dose using image-noise
      (IN)-based determination of X-ray tube settings compared with a body mass index
      (BMI)-based protocol during CT coronary angiography (CTCA). METHODS: Two hundred
      consecutive patients referred for CTCA to our institution were divided into two
      groups: BMI-based, 100 patients had CTCA with the X-ray tube current adjusted to
      the patient's BMI while maintaining a fixed tube potential of 120 kV; IN-based,
      100 patients underwent imaging with the X-ray tube current and voltage adjusted
      to the IN measured within the mid-left ventricle on a pre-acquisition trans-axial
      image. Two independent cardiac radiologists performed blinded image quality
      assessment with quantification of the IN and signal-to-noise ratio (SNR) from the
      mid-LV and qualitative assessment using a three-point score. Radiation dose (CTDI
      and DLP) was recorded from the console. RESULTS: Results showed: IN (HU): BMI
      based, 30.1 +/- 9.9; IN-based, 33.1 +/- 6.7; 32 % variation reduction (P =
      0.001); SNR: BMI-based, 18.6 +/- 7.1; IN-based, 15.4 +/- 3.7; 48 % variation
      reduction (P < 0.0001). Visual scores: BMI-based, 2.3 +/- 0.6; IN-based, 2.2 +/-
      0.5 (P = 0.54). Radiation dose: CTDI (mGy), BMI-based, 22.68 +/- 8.9; IN-based,
      17.16 +/- 7.6; 24.3 % reduction (P < 0.001); DLP (mGy.cm), BMI-based, 309.3 +/-
      127.5; IN-based, 230.6 +/- 105.5; 25.4 % reduction (P < 0.001). CONCLUSIONS:
      Image-noise-based stratification of X-ray tube parameters for CTCA results in 32
      % improvement in image quality and 25 % reduction in radiation dose compared with
      a BMI-based protocol. KEY POINTS: * Image quality and radiation dose are closely
      related in CT coronary angiography. * So too are the image quality, radiation
      dose and body mass index (BMI). * An image-noise-based CTCA protocol reduces the
      radiation dose by 25 %. * It improves inter-patient image homogeneity by 32 %.

PMID- 23949726
TI  - Measuring hepatic functional reserve using low temporal resolution Gd-EOB-DTPA
      dynamic contrast-enhanced MRI: a preliminary study comparing galactosyl human
      serum albumin scintigraphy with indocyanine green retention.
AB  - OBJECTIVE: To investigate if tracer kinetic modelling of low temporal resolution
      dynamic contrast-enhanced (DCE) MRI with Gd-EOB-DTPA could replace technetium-99
      m galactosyl human serum albumin (GSA) single positron emission computed
      tomography (SPECT) and indocyanine green (ICG) retention for the measurement of
      liver functional reserve. METHODS: Twenty eight patients awaiting liver resection
      for various cancers were included in this retrospective study that was approved
      by the institutional review board. The Gd-EOB-DTPA MRI sequence acquired five
      images: unenhanced, double arterial phase, portal phase, and 4 min after
      injection. Intracellular contrast uptake rate (UR) and extracellular volume (Ve)
      were calculated from DCE-MRI, along with the ratio of GSA radioactivity of liver
      to heart-plus-liver and per cent of cumulative uptake from 15-16 min (LHL15 and
      LU15, respectively) from GSA-scintigraphy. ICG retention at 15 min, Child-Pugh
      cirrhosis score (CPS) and postoperative Inuyama fibrosis criteria were also
      recorded. Statistical analysis was with Spearman rank correlation analysis.
      RESULTS: Comparing MRI parameters with the reference methods, significant
      correlations were obtained for UR and LHL15, LU15, ICG15 (all 0.4-0.6, P < 0.05);
      UR and CPS (-0.64, P < 0.001); Ve and Inuyama (0.44, P < 0.05). CONCLUSION:
      Measures of liver function obtained by routine Gd-EOB-DTPA DCE-MRI with tracer
      kinetic modelling may provide a suitable method for the evaluation of liver
      functional reserve. KEY POINTS: * Magnetic resonance imaging (MRI) provides new
      methods of measuring hepatic functional reserve. * DCE-MRI with Gd-EOB-DTPA
      offers the possibility of replacing scintigraphy. * The analysis method can be
      used for preoperative liver function evaluation.

PMID- 23949727
TI  - High-pitch dual-source CT coronary angiography with low volumes of contrast
      medium.
AB  - OBJECTIVES: To assess the effect of lower volumes of contrast medium (CM) on
      image quality in high-pitch dual-source computed tomography coronary angiography
      (CTCA). METHODS: One-hundred consecutive patients (body weight 65-85 kg, stable
      heart rate <=65 bpm, cardiac index >=2.5 L/min/m(2)) referred for CTCA were
      prospectively enrolled. Patients were randomly assigned to one of five groups of
      different CM volumes (G30, 30 mL; G40, 40 mL; G50, 50 mL; G60, 60 mL; G70, 70 mL;
      flow rate 5 mL/s each, iodine content 370 mg/mL). Attenuation within the proximal
      and distal coronary artery segments was analysed. RESULTS: Mean attenuation for
      men and women ranged from 345.0 and 399.1 HU in G30 to 478.2 and 571.8 HU in G70.
      Mean attenuation values were higher in groups with higher CM volumes (P < 0.0001)
      and higher in women than in men (P < 0.0001). The proportions of segments with
      attenuation of at least 300 HU in G30, G40, G50, G60 and G70 were 89 %, 95 %, 98
      %, 98 % and 99 %. CM volume of 30 mL in women and 40 mL in men proved to be
      sufficient to guarantee attenuation of at least 300 HU. CONCLUSIONS: In selected
      patients high-pitch dual-source CTCA can be performed with CM volumes of 40 mL in
      men or 30 mL in women. KEY POINTS: * High-pitch dual-source coronary angiography
      is feasible with low contrast media volumes. * Traditional injection rules still
      apply: higher volumes result in higher enhancement. * The patient's gender is a
      co-factor determining the level of contrast enhancement. * Volumes can be reduced
      down to 30-40 mL in selected patients.

PMID- 23949729
TI  - Strategies for enhancing the production of penicillin G acylase from Bacillus
      badius: influence of phenyl acetic acid dosage.
AB  - Bacillus badius isolated from soil has been identified as potential producer of
      penicillin G acylase (PGA). In the present study, batch experiments performed at
      optimized inoculum size, temperature, pH, and agitation yielded a maximum PGA of
      9.5 U/ml in shake flask. The experiments conducted in bioreactor with different
      oxygen flow rates revealed that 0.66 vvm oxygen flow rate could be sufficient for
      the maximum PGA activity of 12.7 U/ml. From a detailed investigation on the
      strategies of the addition of phenyl acetic acid (PAA) for increasing the
      production of PGA, it was found that the controlled addition of 10 ml of 0.1 %
      (w/v) PAA once in every 2 h from 6th hour of growth showed the maximum PGA
      activity of 32 U/ml. Thus, our studies for the first time showed that at
      concentration above 0.1 % (w/v) PAA, the PGA production decreased. This selective
      condition paves the way for less costly bioprocess for the production of PGA. 

PMID- 23949730
TI  - Platelet count--to wait or not to wait? That is the question.

PMID- 23949728
TI  - Gene expression resulting from PrPC ablation and PrPC overexpression in murine
      and cellular models.
AB  - The cellular prion protein (PrP(C)) plays a key role in prion diseases when it
      converts to the pathogenic form scrapie prion protein. Increasing knowledge of
      its participation in prion infection contrasts with the elusive and controversial
      data regarding its physiological role probably related to its pleiotropy, cell
      specific functions, and cellular-specific milieu. Multiple approaches have been
      made to the increasing understanding of the molecular mechanisms and cellular
      functions modulated by PrP(C) at the transcriptomic and proteomic levels. Gene
      expression analyses have been made in several mouse and cellular models with
      regulated expression of PrP(C) resulting in PrP(C) ablation or PrP(C)
      overexpression. These analyses support previous functional data and have yielded
      clues about new potential functions. However, experiments on animal models have
      shown moderate and varied results which are difficult to interpret. Moreover,
      studies in cell cultures correlate little with in vivo counterparts. Yet, both
      animal and cell models have provided some insights on how to proceed in the
      future by using more refined methods and selected functional experiments. 

PMID- 23949731
TI  - Blood pressure and anthropometrics of 4-y-old children born after preimplantation
      genetic screening: follow-up of a unique, moderately sized, randomized controlled
      trial.
AB  - BACKGROUND: Recent studies suggest that in vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI) are associated with suboptimal
      cardiometabolic outcome in offspring. It is unknown whether preimplantation
      genetic screening (PGS), which involves embryo biopsy, affects blood pressure
      (BP), anthropometrics, and the frequency of received medical care. METHODS: In
      this prospective multicenter follow-up study, we assessed BP, anthropometrics,
      and received medical care of 4-y-old children born to women who were randomly
      assigned to IVF/ICSI with PGS (n = 49) or without PGS (controls; n = 64). We
      applied linear and generalized linear mixed-effects models to investigate
      possible effects of PGS. RESULTS: BP in the PGS and control groups was similar:
      102/64 and 100/64 mm Hg, respectively. Main anthropometric outcomes in the PGS
      vs. control group were: BMI: 16.1 vs. 15.8; triceps skinfold: 108 vs. 98 mm; and
      subscapular skinfold: 54 vs. 53 mm (all P values > 0.05). More PGS children than
      controls had received paramedical care (speech, physical, or occupational
      therapy: 14 (29%) vs. 9 (14%); P = 0.03 in multivariable analysis). The frequency
      of medicial treatment was comparable. CONCLUSION: PGS does not seem to affect BP
      or anthropometrics in 4-y-old children. The higher frequency of received
      paramedical care after PGS may suggest an effect of PGS on subtle developmental
      parameters.

PMID- 23949733
TI  - Competition by aquifer materials in a bimetallic nanoparticle/persulfate system
      for the treatment of trichloroethylene.
AB  - It has been suggested in the literature that aquifer materials can compete with
      the target organic compounds in an activated peroxygen system. In this study, we
      employed a rapid treatment method using persulfate activated with bimetallic
      nanoparticles to investigate the competition between aquifer materials and the
      dissolved phase of a target organic compound. The concentration of dissolved
      trichloroethylene (TCE) remaining after using the activated persulfate system was
      two- to three-fold higher in a soil slurry batch system than in an aqueous batch
      system. For all five aquifer materials investigated, an increase in the mass of
      the aquifer solids significantly decreased the degradation of TCE. A linear
      relationship was observed between the mass of aquifer materials and the initial
      TCE degradation rate, suggesting that the organic carbon and/or aquifer material
      constituents (e.g., carbonates and bicarbonates) compete with the oxidation of
      TCE. 

PMID- 23949732
TI  - Alpha-tocopherol in the brain tissue preservation of stroke-prone spontaneously
      hypertensive rats.
AB  - Oxidative stress has an important role in neuronal damage during cerebral
      ischemia and can lead to cognitive and behavioral impairment. Alpha-tocopherol, a
      powerful antioxidant, may be able to preserve neuronal tissue and circumvent
      neurological deficits. Thus, this study aimed to investigate the influence of
      alpha-tocopherol in the preservation of brain tissue and the maintenance of
      memory formation in stroke-prone spontaneously hypertensive rats (SHRSP). To
      achieve this aim, twenty-four 15-week-old male SHRSP rats were separated into the
      following four groups (n = 6 each) that received different treatments over a 4
      week period: the alpha-tocopherol group, the control group, the L-NAME group, and
      the L-NAME + alpha-tocopherol group. We evaluated the physiological parameters
      (body weight, diuresis, and food and water intake), an oxidative stress marker
      (malondialdehyde levels), and neurological responses (the Morris Water Maze and
      Novel Objects Recognition tests). Afterwards, the brains were removed for
      histopathological analysis and quantification of the number of cells in the
      hippocampus. Statistically, the alpha-tocopherol group demonstrated better
      results when compared to all groups. The data indicated a reduction in oxidative
      stress and the preservation of neurological responses in groups treated with
      alpha-tocopherol. In contrast, the L-NAME group exhibited increased
      malondialdehyde levels, impairment of neurological responses, and several
      hippocampus tissue injuries. The others groups exhibited nerve tissue changes
      that were restricted to the glial nodes. No significant alterations were observed
      in the physiologic parameters. Based on these findings, we suggest that alpha
      tocopherol can prevent stroke, preserve the structure of the hippocampus, and
      maintain both memory and cognition functions. 

PMID- 23949734
TI  - The combined treatment with orbital and pretarsal botulinum toxin injections in
      the management of poorly responsive blepharospasm.
AB  - Blepharospasm (BS) is a focal dystonia involving involuntary contractions of
      muscles around the eyes. Botulinum toxin (BoNT) is the most effective treatment
      for BS and the technique of injection changes depending on the clinical picture.
      Usually typical BS benefits from the injection in the orbital part of the
      orbicularis oculi (OOc) muscle (orbital injection), while BoNT injection in the
      pretarsal part of OOc muscle is helpful especially for the atypical BS (opening
      eyelid apraxia). The aim of this study was to compare the efficacy of two
      injection techniques, the orbital versus the combined (injection in both orbital
      and pretarsal part of OOc) in BS patients with unsatisfactory response to BoNT.
      Nineteen patients with typical BS not having a satisfactory response from BoNT
      treatment with the orbital injection (primary and secondary resistant patients)
      were studied. After 3 months from the last orbital injection patients received
      the combined injection; they were assessed with the JRS and BSDI scales after 4
      weeks from the last orbital and the first combined injection. Statistical
      analysis showed a significant reduction (p < 0.05) of the mean score of JRS and
      BSDI scales comparing the combined with orbital injection. This study shows that
      the treatment of typical BS can have better results when BoNT is injected with
      the combined technique in primary and secondary resistant patients.

PMID- 23949735
TI  - [Abdominal pain after gallstone ileus operation].

PMID- 23949736
TI  - [Dynamic tumor in the right liver lobe].

PMID- 23949737
TI  - RNA-binding protein RBM8A (Y14) and MAGOH localize to centrosome in human A549
      cells.
AB  - RBM8A (Y14) is carrying RNA-binding motif and forms the tight heterodimer with
      MAGOH. The heterodimer is known to be a member of exon junction complex on
      exporting mRNA and is required for mRNA metabolisms such as splicing, mRNA export
      and nonsense-mediated mRNA decay. Almost all RBM8A-MAGOH complexes localize in
      nucleoplasm and shuttle between nuclei and cytoplasm for RNA metabolism.
      Recently, the abnormality of G2/M transition and aberrant centrosome regulation
      in RBM8A- or MAGOH-deficient cells has been reported. These results prompt us to
      the reevaluation of the localization of RBM8A-MAGOH in human cells.
      Interestingly, our immunostaining experiments showed the localization of these
      proteins in centrosome in addition to nuclei. Furthermore, the transiently
      expressed eYFP-tagged RBM8A and Flag-tagged MAGOH also co-localized with
      centrosome signals. In addition, the proximity ligation in situ assay was
      performed to detect the complex formation in centrosome. Our experiments clearly
      showed that Myc-tagged RBM8A and Flag-tagged MAGOH formed a complex in
      centrosome. GFP-tagged PLK1 also co-localized with Myc-RBM8A. Our results show
      that RBM8A-MAGOH complex is required for M-phase progression via direct
      localization to centrosome rather than indirect effect. 

PMID- 23949739
TI  - Palonosetron and prednisolone for the prevention of nausea and emesis during
      fractionated radiotherapy and 5 cycles of concomitant weekly cisplatin-a phase II
      study.
AB  - PURPOSE: Recommendations for antiemetic prophylaxis supportive to radiotherapy
      and concomitant chemotherapy are not evidence-based. The purpose of this study
      was to evaluate the efficacy of the antiemetic regimen concurrent to fractionated
      radiotherapy and concomitant weekly cisplatin in two Danish departments of
      oncology. METHODS: Patients with gynecological cancer scheduled to receive
      fractionated radiotherapy and concomitant weekly cisplatin (40 mg/m(2)) were
      asked to complete a study diary in order to assess episodes of emesis, grade of
      nausea, and use of rescue antiemetic treatment daily during 5 weeks of treatment.
      Antiemetic treatment consisted of palonosetron and prednisolone. A patient had
      completed the study if emesis occurred or if 5 weeks of treatment were
      accomplished without emesis. The primary endpoint was sustained no emesis during
      5 weeks of treatment. RESULTS: A total of 48 patients completed 155 weekly cycles
      of radiotherapy, concomitant weekly cisplatin, and antiemetic prophylaxis. The
      probability of completing 5 cycles without emesis (sustained no emesis) was 57 %.
      During cycle 1, 42 % of the patients were free from nausea. After 5 cycles, only
      23 % of patients were continuously free from nausea. One half of the patients
      used rescue antiemetic treatment at least once during the 5 cycles. CONCLUSION:
      The present study demonstrates that an antiemetic prophylaxis consisting of
      palonosetron and prednisolone is insufficient for the prevention of nausea and
      vomiting induced by radiotherapy and weekly cisplatin in patients treated for
      gynecological cancer. The addition of a neurokinin-1 receptor antagonist should
      be investigated in a randomized, double-blind study in this setting.

PMID- 23949740
TI  - Changes of QTc interval after opioid switching to oral methadone.
AB  - A consecutive sample of patients who were switched from strong opioids to
      methadone in a period of 1 year was surveyed. QTc was assessed before switching
      (T0) and after achieving adequate analgesia and an acceptable level of adverse
      effects (Ts). Twenty-eight of 33 patients were switched to methadone
      successfully. The mean initial methadone doses at T0 were 67.1 mg/day (SD +/
      80.2, range 12-390). The mean QTc interval at T0 was 400 ms (SD +/-30, range 330
      450). The mean QTc interval at Ts (median 5 days) was 430 ms (SD +/-26, range 390
      500). The difference (7.7 %) was significant (p < 0.0005). Only two patients had
      a QTc of 500 ms. No serious arrhythmia was observed. At the linear regression
      analysis, there was no significant association between mean opioid doses
      expressed as oral morphine equivalents and QTc at T0 (p = 0.428), nor between
      mean methadone doses and QTc at Ts (p = 0.315). No age differences were found
      with previous opioid doses (p = 0.917), methadone doses (p = 0.613), QTc at T0 (p
      = 0.173), QTc at Ts (p = 0.297), and final opioid-methadone conversion ratio (p =
      0.064). While methadone used for opioids switching seems to be an optimal choice
      to improve the opioid response in patients poorly responsive to the previous
      opioid, the possible QTc prolongation should be of concern despite not producing
      clinical consequences in this group of patients. A larger number of patients
      should be assessed to quantify the risk of serious arrhythmia. 

PMID- 23949741
TI  - The utility of nodule volume in the context of malignancy prediction for small
      pulmonary nodules.
AB  - BACKGROUND: An estimated 150,000 pulmonary nodules are identified each year, and
      the number is likely to increase given the results of the National Lung Screening
      Trial. Decision tools are needed to help with the management of such pulmonary
      nodules. We examined whether adding any of three novel functions of nodule volume
      improves the accuracy of an existing malignancy prediction model of CT scan
      detected nodules. METHODS: Swensen's 1997 prediction model was used to estimate
      the probability of malignancy in CT scan-detected nodules identified from a
      sample of 221 patients at the Medical University of South Carolina between 2006
      and 2010. Three multivariate logistic models that included a novel function of
      nodule volume were used to investigate the added predictive value. Several
      measures were used to evaluate model classification performance. RESULTS: With
      use of a 0.5 cutoff associated with predicted probability, the Swensen model
      correctly classified 67% of nodules. The three novel models suggested that the
      addition of nodule volume enhances the ability to correctly predict malignancy;
      83%, 88%, and 88% of subjects were correctly classified as having malignant or
      benign nodules, with significant net improved reclassification for each
      (P<.0001). All three models also performed well based on Nagelkerke R2,
      discrimination slope, area under the receiver operating characteristic curve, and
      Hosmer-Lemeshow calibration test. CONCLUSIONS: The findings demonstrate that the
      addition of nodule volume to existing malignancy prediction models increases the
      proportion of nodules correctly classified. This enhanced tool will help
      clinicians to risk stratify pulmonary nodules more effectively.

PMID- 23949742
TI  - Enrichment of epidermal stem cells of rats by Vario magnetic activated cell
      sorting system.
AB  - Epidermal stem cells (ESCs) play an important role in skin homeostasis, wound
      repair, and tumorigensis which have great potential in scientific research and
      clinical application. So, the efficient isolation of these infrequent stem cells
      is very important for researchers to solve the problem of low purity and
      insufficient quantity of stem cells in vitro. The aim of this study was to
      investigate a method for the enrichment of ESCs by magnetic activated cell
      sorting system. The isolation strategy was CD71 depletion followed by alpha6
      integrin positive selection. The percentage of alpha6(bri)CD71(dim) cells in
      isolated cells was 94.59%. Transmission electron microscopy results revealed that
      alpha6(bri) CD71(dim) cells exhibited some typical characteristics like
      progenitor cells, such as big nucleus, obvious nucleolus, large nuclear-cytoplasm
      ratio, and few organelles in cytoplasm. When cultured in vitro, the
      alpha6(bri)CD71(dim) cells had greater proliferating potential and higher colony
      forming ability, and high levels of epidermal stem cell markers were expressed in
      our positive cells. ESCs have been successfully isolated from neonatal epidermis
      using Vario MACS and cultured in vitro. This isolation method is simple, fast,
      and inexpensive, providing an important tool for tissue engineering and cell
      transplantation studies. 

PMID- 23949743
TI  - Bladder cancer cell in co-culture induces human stem cell differentiation to
      urothelial cells through paracrine FGF10 signaling.
AB  - Fibroblast growth factor 10 (FGF10) is required for embryonic epidermal
      morphogenesis including brain development, lung morphogenesis, and initiation of
      limb bud formation. In this study, we investigated the role of FGF10 as a lead
      induction factor for stem cell differentiation toward urothelial cell. To this
      end, human multipotent stem cell in vitro system was employed. Human amniotic
      fluid stem cells were co-cultured with immortalized bladder cancer lines to
      induce directed differentiation into urothelial cells. Urothelial markers,
      uroplakin II, III, and cytokeratin 8, were monitored by RT-PCR,
      immunocytochemistry, and Western blot analysis. Co-cultured stem cells began to
      express uroplakin II, III, and cytokeratin 8. Targeted FGF10 gene knockdown from
      bladder cancer cells abolished the directed differentiation. In addition, when
      FGF10 downstream signaling was blocked with the Mek inhibitor, the co-culture
      system lost the capacity to induce urothelial differentiation. Exogenous addition
      of recombinant FGF10 protein promoted stem cell differentiation into urothelium
      cell lineage. Together, this report suggests that paracrine FGF10 signaling
      stimulates the differentiation of human stem cell into urothelial cells. Current
      study provides insight into the potential role of FGF10 as a lead growth factor
      for bladder regeneration and its therapeutic application for bladder
      transplantation. 

PMID- 23949744
TI  - History and contemporary perspectives of the integrated pest management of
      soybean in Brazil.
AB  - The integrated pest management (IPM) of soybean developed and implemented in
      Brazil was one of the most successful programs of pest management in the world.
      Established during the 1970s, it showed a tremendous level of adoption by
      growers, decreasing the amount of insecticide use by over 50%. It included
      outstanding approaches of field scouting and decision making, considering the
      economic injury levels (EILs) for the major pests. Two main biological control
      programs were highly important to support the soybean IPM program in Brazil,
      i.e., the use of a NPVAg to control the major defoliator, the velvet bean
      caterpillar, Anticarsia gemmatalis Hubner, and the use of egg parasitoids against
      the seed-sucking stink bugs, in particular, the southern green stink bug, Nezara
      viridula (L.). These two biological control programs plus pests scouting, and the
      use of more selective insecticides considering the EILs supported the IPM program
      through the 1980s and 1990s. With the change in the landscape, with the adoption
      of the no-tillage cultivation system and the introduction of more intense
      multiple cropping, and with the lower input to divulge and adapt the IPM program
      to this new reality, the program started to decline during the years 2000s.
      Nowadays, soybean IPM is almost a forgotten control technology. In this mini
      review article, suggestions are made to possibly revive and adapt the soybean IPM
      to contemporary time. 

PMID- 23949745
TI  - Patterns of ant (Hymenoptera: Formicidae) richness and relative abundance along
      an aridity gradient in Western Venezuela.
AB  - In xeric ecosystems, ant diversity response to aridity varies with rainfall
      magnitude and gradient extension. At a local scale and with low precipitation
      regimes, increased aridity leads to a reduction of species richness and an
      increased relative abundance for some ant species. In order to test this pattern
      in tropical environments, ant richness and relative abundance variation were
      evaluated along 35 km of an aridity gradient in the Araya Peninsula, state of
      Sucre, Venezuela. Three sampling stations comprising five transects each were set
      up. Pitfall traps and direct collecting from vegetation were assessed per
      transect. Overall, 52 species, 23 genera, and 7 subfamilies of ants were recorded
      in the peninsula. The total number of species and genera recorded by both
      sampling stations and transects decreased linearly with increasing aridity. Total
      relative abundance was highest in the most arid portion of the peninsula, with
      Crematogaster rochai (Forel) and Camponotus conspicuus zonatus (Emery)
      (Hymenoptera: Formicidae) being the numerically dominant species. Spatial and
      multivariate analyses revealed significant changes in ant composition every 11 km
      of distance, and showed a decrease of ant diversity with the increase of harsh
      conditions in the gradient. Here, we discuss how local geographic and topographic
      features of Araya originate the aridity gradient and so affect the microhabitat
      conditions for the ant fauna. 

PMID- 23949746
TI  - Estimates of genetic relatedness among males in a polygynous wasp.
AB  - Cyclical oligogyny is considered to be the mechanism that is most likely to be
      responsible for stabilizing cooperation in polygynous, epiponine wasps, in which
      single-queen colonies produce new queens and multiple-queen colonies produce
      males. In contrast with the number of studies on relatedness among adult females,
      we know little about relatedness among males in polygynous epiponine wasps. We
      estimated worker and male relatedness in the Brazilian epiponine wasp Polybia
      paulista Ihering and found that colonies of P. paulista produced males when they
      contained multiple queens. Although average relatedness within males did not
      differ significantly from 0.5, the number of alleles observed suggests that there
      were more than one queen to produce males in each colony. Our data would be
      helpful to elucidate dynamics of the male production in a colony of epiponine
      wasps. 

PMID- 23949747
TI  - Population dynamics of Dichelops melacanthus (Dallas) (Heteroptera: Pentatomidae)
      on Host Plants.
AB  - The stink bug Dichelops melacanthus (Dallas) has become one of the major pests of
      corn and wheat in Brasil, mainly after a shift from the conventional tillage
      system to the no tillage cultivation system. This fact may be due to the
      simultaneous occurrence of second planting corn with wheat cultivation, and the
      presence of wild hosts. This study aimed to evaluate the population dynamics of
      D. melacanthus on wild hosts adjacent to areas cultivated with corn, wheat, and
      soybean during the season and off-season of soybean cultivation. Weekly surveys
      were conducted in the region of Londrina, PR, Brasil from the beginning of July
      2007 up to the end of June 2008 using the square meter method. Corn (Zea mays),
      soybean (Glycine max), tropical spiderwort (Commelina benghalensis), hairy indigo
      (Indigofera hirsuta), crotalaria (Crotalaria pallida), wheat (Triticum aestivum),
      and signal grass (Brachiaria decumbens) were identified as hosts of D.
      melacanthus. Signal grass was the host in which stink bug adults were found in
      higher numbers, while nymphs and adults were consistently collected on tropical
      spiderwort. Although nymphs completed their development on tropical spiderwort
      seeds, this host was found less suitable than soybean seeds. 

PMID- 23949748
TI  - Ithomiini butterflies (Lepidoptera: Hymphalidae) of Antioquia, Colombia.
AB  - Colombia is one of the most biodiverse countries on the planet. However, economic
      and scientific investment in completing inventories of its biodiversity has been
      relatively poor in comparison with other Neotropical countries. Butterflies are
      the best studied group of invertebrates, with the highest proportion of known to
      expected species. More than 3,200 species of butterflies have been recorded in
      Colombia, although the study of the still many unexplored areas will presumably
      increase this number. This work provides a list of Ithomiini butterflies
      collected in the department of Antioquia and estimates the total number of
      species present, based on revision of entomological collections, records in the
      literature and field work performed between 2003 and 2011. The list includes 99
      species and 32 genera, representing 27% of all Ithomiini species. We report 50
      species of Ithomiini not formerly listed from Antioquia, and found the highest
      diversity of ithomiine species to be at middle elevations (900-1,800 m). The mean
      value of the Chao2 estimator for number of species in Antioquia is 115 species,
      which is close to a predicted total of 109 based on known distributions of other
      Ithomiini not yet recorded from the department. Nine species are potentially of
      particular conservation importance because of their restricted distributions, and
      we present range maps for each species. We also highlight areas in Antioquia with
      a lack of biodiversity knowledge to be targeted in future studies. This paper
      contributes to mapping the distribution of the Lepidoptera of Antioquia
      department in particular and of Colombia in general. 

PMID- 23949750
TI  - Assessment of patterns of fluctuating asymmetry and sexual dimorphism in carabid
      body shape.
AB  - The measurement tool most used to estimate developmental stability (DS) is
      fluctuating asymmetry (FA), which is a measure of the small random deviations
      that occur between the left and right sides of bilaterally symmetrical traits. In
      the Biobio Region of Chile, forest plantations are a widely extended phenomenon,
      which affect 27% of the surface area of the region and which are dominated by the
      monoculture of Pinus radiata. This study evaluated the presence of FA in the body
      shape of two populations of Ceroglossus chilensis (Eschscholtz) in two 13-year
      old forest plantations (commercial thinning) using insects collected with
      interception traps. Since the biotic and abiotic components of forest plantations
      are subject to continual anthropic modifications that affect almost all
      ecological processes, including population dynamics, community composition, and
      material and energy flows, these characteristics are reflected in the DS of
      individuals. The results showed that there was greater precision using geometric
      morphometrics to detect the presence of asymmetry in plantations due to shape
      analysis, as proposed by studies in antennal morphology using traditional
      measures. It should be noted that the populations were exposed to different
      environments; the population in the Coast Range is more humid, while the Andes
      Foothills population is in a drier area with drier soils. In spite of this, there
      was minimum phenotypic variation detected at the population level, which
      reflected the different environments and may be associated with patterns of
      environmental phenotypic plasticity. 

PMID- 23949749
TI  - Sex differences in piercing-sucking sites on leaves of Ligustrum lucidum
      (Oleaceae) infested by the Chinese white wax scale insect, Ericerus pela
      (Chavannes) (Hemiptera: Coccidae).
AB  - The type of host tissues and cells ingested by piercing and sucking insects
      greatly affects their nutrient intake, which may subsequently affect insect
      fitness. This study describes the sex differences in feeding site selection
      between male and female nymphs of the Chinese white wax scale insect (CWWS),
      Ericerus pela (Chavannes), feeding on leaves of the Chinese privet, Ligustrum
      lucidum. Our data showed that the stylet tips of female nymphs terminated in the
      phloem sieve elements of main or lateral veins, while those of male nymphs
      terminated in the palisade parenchyma. We concluded that female nymphs fed from
      sieve elements and males fed from parenchyma cells. The potential impact of these
      feeding patterns was discussed in relation to the selection of a site for
      attachment, nutrient acquisition, and mouthpart stretching mechanism. Among these
      factors, selection of a site for attachment and mouthpart stretching mechanism
      may be the main cause of sex differences in feeding sites between female and male
      nymphs of CWWS. 

PMID- 23949751
TI  - Contribution to the knowledge of the andean stonefly genus Claudioperla illies,
      with description of new apterous and micropterous species (Plecoptera:
      Gripopterygidae).
AB  - The genus Claudioperla (Plecoptera: Gripopterygidae), which has been reported
      from Chile and Argentina to Colombia, was until now monospecific. The study of
      adults from various localities of the Bolivian Altiplano has resulted in the
      discovery of four distinct species. Three are new and described: Claudioperla
      rosalesi n. sp., Claudioperla moyai n. sp., and Claudioperla ruhieri n. sp. The
      fourth, Claudioperla tigrina (Klapalek), presents morphological variations with
      previous descriptions that are exposed and discussed. One of the new species, C.
      ruhieri, is apterous. The male of C. moyai is micropterous. Among South American
      stoneflies, they are the first cases of aptery and microptery reported outside of
      Patagonia. Adapted to extreme conditions of temperature and altitude, C. moyai
      and C. ruhieri are particularly threatened by the recent evolution of Bolivian
      glaciers. 

PMID- 23949752
TI  - Morphology of immatures of Caonabo pseudoscylax (Bergroth) (Hemiptera:
      Pentatomidae).
AB  - Characters of immatures are potentially useful in identifying taxa, but few
      immatures of Pentatomidae were described. The objectives here are to describe the
      egg and five nymphal instars of Caonabo pseudoscylax (Bergroth) under light and
      scanning electron microscopy. Adults, eggs, and nymphs were collected on
      Homolepsis glutinosa during 2008, in Criciuma (Santa Catarina, Brazil). The egg
      of C. pseudoscylax is subcylindrical, chorion reddish brown, slightly
      translucent, and with granulate surface. Aero-micropylar processes translucent,
      spongy, and strongly clavate. Nymphs without punctures, spiracles placed near the
      lateral abdominal margin. The dorsal abdominal gland has rounded ostioles bearing
      cuticular valve; spout peritreme smooth, directed anteriorly; evaporatorium
      network-shaped; and microsculpture poorly ornamented. Humeral angles of the
      pronotum were produced from fourth instar. The almost marginal placement of
      abdominal spiracles may diagnose the nymphs of C. pseudoscylax from first instar
      to adulthood. 

PMID- 23949753
TI  - Predatory potential of Euseius alatus (Phytoseiidae) on different life stages of
      Oligonychus ilicis (Tetranychidae) on coffee leaves under laboratory conditions.
AB  - This study evaluated the predatory capacity of Euseius alatus (DeLeon) as a
      biological control agent of the pest mite Oligonychus ilicis (McGregor) on coffee
      leaves under laboratory conditions, using arenas containing 25 O. ilicis per
      coffee (Coffea arabica) leaf to one specimen of each stage of the predator mite.
      The functional response and oviposition rate of adult females of E. alatus were
      evaluated on coffee leaf arenas and offered from 1 to 125 immature stages of O.
      ilicis per arena. The number of preys killed and the number of eggs laid by the
      predator were evaluated every 24 h during 8 days. The preys consumed were daily
      replaced. Male and female adults of E. alatus were the most efficient in killing
      all developmental stages of O. ilicis. Larvae and nymphs of O. ilicis were the
      most consumed by all stages of the predatory mite. The functional response and
      oviposition rates of E. alatus increased as the prey density increased, with a
      positive and highly significant correlation. Regression analysis suggested a type
      II functional response, with a maximum predation of 22 O. ilicis/arena and a
      maximum oviposition rate of 1.7 eggs/day at a density of 70 O. ilicis/arena. 

PMID- 23949754
TI  - Cannibalism and virus production in Spodoptera frugiperda (J.E. Smith)
      (Lepidoptera: Noctuidae) larvae fed with two leaf substrates inoculated with
      Baculovirus spodoptera.
AB  - Cannibalism in the fall armyworm, Spodoptera frugiperda (J.E. Smith)
      (Lepidoptera: Noctuidae) (FAW), is a limiting factor in a baculovirus production
      system. To detect the impact of cannibalism, a two-step bioassay was conducted
      with different larval ages of FAW fed on two food sources (corn and castor bean
      leaves) contaminated with the S. frugiperda multiple-embedded
      nucleopolyhedrovirus. In a first bioassay, the food source affected the
      cannibalism, being higher for all larval ages tested (5-, 6- and 7-day-old
      larvae) in larvae fed on corn than on those fed on castor bean leaves. Larval
      mortality, weight equivalent and larval equivalents (LEs) per hectare decreased
      as the larval age increased. Larval weight, occlusion bodies (OBs)/larva and
      total OBs increased when the larval age increased. In a second bioassay, in which
      only 6- and 7-day-old larvae were used because of the performance in the first
      bioassay, the cannibalism rates were affected by the interaction between food
      sources and time of feeding (48 and 72 h), reaching the highest values for 6- and
      7-day-old larvae fed on corn leaves for 72 h. Mortality of the FAW was affected
      by the interaction between food sources, larval age and time of feeding. The
      lowest mortalities were on 7-day-old larvae when they were fed on castor bean
      leaves for 48 and 72 h. Larval weight, OBs/larva, total OBs and LEs were affected
      by the interaction between food sources and larval age. A significant correlation
      was observed between larval weight and OBs/larva that fed on both food sources,
      suggesting that larval weight can be used to achieve a concentration to be
      sprayed in 1 ha. 

PMID- 23949755
TI  - Sequential sampling plan for Tenuipalpus heveae Baker (Acari: Tenuipalpidae) on
      rubber tree.
AB  - The objective of the present study was to develop a sequential sampling plan for
      the decision-making process to control Tenuipalpus heveae Baker (Acari:
      Tenuipalpidae), an important pest of the rubber tree crop. The experimental area
      was represented by 1,000 plants of the RRIM 600 clone divided in 100 plots with
      10 plants each. Leaves were collected and the number of mites determined under
      laboratory conditions. The sequential sampling plan was developed in accordance
      with the Sequential Test Likelihood Ratio. The value 0.10 was pre-established for
      alpha and beta representing type I and type II errors, respectively. The level of
      control adopted was six mites per 12 cm(2). The operating characteristic curve
      and the curve of maximum expected sample were determined. Two lines were
      generated: the upper one, when the condition for chemical control is recommended
      (S1 = 23.3080 + 2.1972); and the lower, when chemical control is not recommended
      (S0 = -23.3080 + 2.1972). Sample size for the decision-making process to control
      T. heveae requires 6 to 18 plants. 

PMID- 23949756
TI  - Response of Bemisia tabaci Genn. (Hemiptera: Aleyrodidae) biotype B to genotypes
      of pepper Capsicum annuum (Solanales: Solanaceae).
AB  - Bemisia tabaci Genn. biotype B is a widely distributed plant pest that represents
      one of the major constraints for horticultural crop production. The purpose of
      the present work was to evaluate the oviposition preference, survivorship, and
      development of B. tabaci biotype B on semi-cultivated genotypes of Capsicum
      annuum from southeast Mexico. In free-choice experiments to evaluate the
      oviposition preference, lower number of eggs laid by B. tabaci biotype B was
      observed in the genotypes Maax and Xcat'ik relative to that in the commercial
      genotype Parado. Egg hatchability was significantly lower in Pico Paloma, Bolita,
      Blanco, Chawa, Payaso, and Xcat'ik than in the rest of the genotypes, including
      the commercial genotype Jalapeno. Likewise, survivorship of nymphs was
      significantly lower in Pico Paloma, Bolita, and Blanco than in the remaining
      genotypes. Nymph developmental time and the period of development from egg to
      adult were the shortest in Amaxito. Therefore, sources of resistance to B. tabaci
      biotype B by antibiosis (accumulation of plant defense compounds) might be found
      in the semi-cultivated genotypes Pico Paloma, Bolita, and Blanco. 

PMID- 23949757
TI  - Description of immature stages and development time of Paralucilia paraensis
      (Mello) (Diptera: Calliphoridae) associated with the decomposition of a partially
      submerged swine carcass.
AB  - We report on the bionomics and morphology of the immature stages of Paralucilia
      paraensis (Mello) (Diptera: Calliphoridae). Observations were made on a daily
      basis for 10 h (from 8 a.m. to 6 p.m.) on a 45-kg pig (Sus scrofa) whose carcass
      had been partially submerged in a stream of water on the 21st of November 2009,
      in a forested area of Manaus, Amazonas, Brazil. The collected specimens were
      placed in plastic vials and transferred to a growth chamber maintained at room
      temperature. Adults of P. paraensis were collected on the carcass between the 3rd
      and the 18th days. A total of 13 gravid females were captured; from these, 1,240
      eggs were obtained and yielded 1,030 larvae that developed into 879 adults. The
      average time required for hatching was 13 h. On average, the larvae reached the
      second instar within 13 h, third instar within 18 h, and pupae within 46 h. The
      pupal stage lasted 96 h. The complete development time was 216 h. This is the
      first report on the development time and morphology of immature stages of P.
      paraensis in forested areas. Therefore, these results provided information for
      the implementation of future forensic studies in the state of Amazonas. 

PMID- 23949758
TI  - Insects breeding in pig carrion in two environments of a rural area of the state
      of minas gerais, Brazil.
AB  - The main objective of this study was to identify potential forensic indicators in
      the insect fauna associated with pig carrion and the pattern of insect succession
      during the decomposition process in two environments of a rural area in
      Uberlandia, State of Minas Gerais, Brazil. The study was conducted at two
      locations: in a pasture and in a fragment of a semi-deciduous forest (vegetation
      profile of the Cerrado biome) in two different seasons (rainy and dry) of 2010.
      The decomposition process was more rapid in the rainy season. More than 32,000
      insects belonging to 17 species of 6 families of Diptera and 2 species of
      Coleoptera bred in the carcasses. The majority of Diptera bred in the first three
      stages of decomposition. However, Phoridae and Coleoptera bred mainly in the last
      two stages. The insects bred more abundantly in the pasture and in the humid
      season. The exceptions were the Fanniidae (Diptera), which bred more abundantly
      in the forest and the Dermestidae and Cleridae (Coleoptera), which did not
      demonstrate any preference in terms of environments and were more abundant in the
      dry season, respectively. Species such as Chrysomya albiceps (Wiedemann), Peckia
      (Patonella) intermutans (Walker), Necrobia rufipes (De Geer), and Dermestes
      maculatus (De Geer) may be potential indicators of post-mortem interval.
      Hemilucilia segmentaria (Fabricius) and Ophyra aenescens (Wiedemann) may be
      indicators of localization of the natural environment, while Musca domestica
      Linnaeus may be an indicator of the anthropic environment. The study thus
      presented many species of potential forensic indicators in rural areas of this
      region. 

PMID- 23949759
TI  - Preserving dermatology.

PMID- 23949760
TI  - Patient organizations and the investigative dermatology community as partners:
      DEBRA and Epidermolysis bullosa research.

PMID- 23949764
TI  - Progress in Epidermolysis bullosa research: summary of DEBRA International
      Research Conference 2012.

PMID- 23949765
TI  - Making a mountain out of a molehill: NRAS, mosaicism, and large congenital nevi.
AB  - Linking phenotypic patterns of melanocytic neoplasia to specific gene mutations
      allows more precise predicting of clinical behavior and response to targeted
      therapy. In this issue, Kinsler et al. provide evidence that multiple congenital
      nevi with central nervous system lesions are likely exclusively the result of
      mosaic mutations in NRAS. We discuss the link between mosaic NRAS mutations,
      cellular senescence, and clinical phenotype in these nevi. 

PMID- 23949766
TI  - Nuclear topology, epigenetics, and keratinocyte differentiation.
AB  - Recent progress in epigenetics reveals dynamic chromatin interactions in the
      nucleus during development, regeneration, reprogramming, and in disease. Higher
      order chromatin organization is manifested as changes in the topological
      distribution of eu-/heterochromatin and in nuclear morphology. We are now able to
      gain new knowledge about these changes at the genomic level. 

PMID- 23949767
TI  - PUMA: a puzzle piece in chloroquine's antimelanoma activity.
AB  - Chloroquine (CQ) can induce cell death in a subset of cancer cell lines, and some
      melanoma cell lines are quite susceptible. Although it is well known that CQ
      impairs lysosomal function and can serve as an autophagy inhibitor, the molecular
      target of CQ and the subsequent cascade of events that lead to cell death are not
      fully understood. Recent evidence indicates that in melanoma cell lines, CQ
      induces apoptosis by preventing degradation of the pro-apoptotic BH3-only protein
      p53-upregulated modulator of apoptosis. This finding adds to the unfolding story
      of CQ's mechanism of action as a cancer therapeutic agent. 

PMID- 23949768
TI  - Skin-specific drug delivery: a rapid solution to skin diseases?
AB  - In this issue of The Journal of Investigative Dermatology, Kouno et al. achieve
      skin-specific drug delivery using an antibody to deliver substances in a highly
      specific manner to nontransformed cells. They make use of a nonpathogenic anti
      desmoglein 3 autoantibody that had been derived from a patient with pemphigus
      vulgaris to deliver drugs to the surface of keratinocytes. This approach may turn
      out to be a new "magic bullet", thereby revolutionizing the therapy of skin
      disease. The authors then used a conjugate of this antibody with a new drug
      entity, TNF-related apoptosis-inducing ligand, to demonstrate, as a proof-of
      principle, that their approach has the potential to facilitate the treatment of
      both cancerous and inflammatory skin diseases. 

PMID- 23949769
TI  - Mesenchymal cells hold the key to immune cell recruitment to and migration within
      melanoma.
AB  - Samaniego et al. (this issue) report on distinct tumor-associated mesenchymal
      cell (MC) populations in human melanomas. FAP(-)CD90(+) peritumoral MCs may be
      involved in immune cell recruitment from the bloodstream. FAP(+)CD90(-)
      intratumoral MCs were associated with extracellular matrix fiber deposition, and
      their numbers correlated with high immune cell infiltration. Thus, different MC
      subsets modulate the cellular composition of the intratumoral and peritumoral
      melanoma microenvironment. 

PMID- 23949770
TI  - Enzyme immunoassay and enzyme-linked immunosorbent assay.

PMID- 23949772
TI  - Smoking and experiences with tobacco cessation among men who have sex with men:
      New Orleans, 2011.
AB  - Smoking continues to be a problem in the United States, particularly among men
      who have sex with men (MSM). The current study assesses the prevalence of current
      and lifetime smoking as well as cessation experiences in a sample of MSM. Two
      thirds of the sample had ever smoked tobacco and 50 % of MSM were current
      smokers. Prevalence of current smoking in this sample was higher than comparative
      data obtained from HIV positive patients at a local clinical population. Smoking
      was found to be associated with HIV status, race, age, education, income and
      alcohol use. A high proportion of MSMs social networks were smokers especially
      among current smokers. Continued efforts targeting or linking MSM into tobacco
      cessation efforts are recommended. 

PMID- 23949774
TI  - Rhodium-catalyzed oxidative coupling through C-H activation and annulation
      directed by phosphonamide and phosphinamide groups.
AB  - Rhodium-catalyzed oxidative coupling reactions via C-H activation and annulation
      directed by phosphonamide and phosphinamide groups were developed under aerobic
      conditions, which produced benzazaphosphole 1-oxides and phosphaisoquinolin-1
      oxides. 

PMID- 23949773
TI  - Multiple mutant T alleles cause haploinsufficiency of Brachyury and short tails
      in Manx cats.
AB  - Most mammals possess a tail, humans and the Great Apes being notable exceptions.
      One approach to understanding the mechanisms and evolutionary forces influencing
      development of a tail is to identify the genetic factors that influence extreme
      tail length variation within a species. In mice, the Tailless locus has proven to
      be complex, with evidence of multiple different genes and mutations with
      pleiotropic effects on tail length, fertility, embryogenesis, male transmission
      ratio, and meiotic recombination. Five cat breeds have abnormal tail length
      phenotypes: the American Bobtail, the Manx, the Pixie-Bob, the Kurilian Bobtail,
      and the Japanese Bobtail. We sequenced the T gene in several independent lineages
      of Manx cats from both the US and the Isle of Man and identified three 1-bp
      deletions and one duplication/deletion, each predicted to cause a frameshift that
      leads to premature termination and truncation of the carboxy terminal end of the
      Brachyury protein. Ninety-five percent of Manx cats with short-tail phenotypes
      were heterozygous for T mutations, mutant alleles appeared to be largely lineage
      specific, and a maximum LOD score of 6.21 with T was obtained at a recombination
      fraction (Theta) of 0.00. One mutant T allele was shared with American Bobtails
      and Pixie-Bobs; both breeds developed more recently in the US. The ability of
      mutant Brachyury protein to activate transcription of a downstream target was
      substantially lower than wild-type protein. Collectively, these results suggest
      that haploinsufficiency of Brachyury is one mechanism underlying variable tail
      length in domesticated cats. 

PMID- 23949776
TI  - Effects of Cymbopogon citratus and Ferula assa-foetida extracts on glutamate
      induced neurotoxicity.
AB  - Many of CNS diseases can lead to a great quantity of release of glutamate and the
      extreme glutamate induces neuronal cell damage and death. Here, we wanted to
      investigate the effects of Cymbopogon citratus essential oil and Ferula assa
      foetida extracts treatment on glutamate-induced cell damage in a primary culture
      of rat cerebellar granule neurons. Cerebellums were collected from 7-d rat brains
      and cerebellar granule neurons were obtained after 8-d culture. CGN cells were
      treated with C. citratus essential oil and F. assa-foetida extracts at
      concentration of 100 MUg/ml before, after, and during exposure to 30 MUM
      glutamate. The cellular viability was evaluated by 3-(4, 5-dimethytthiazol-2-yl)
      2, 5-diphenyltetrazoliumbromide (MTT) staining. The flow cytometry assay was used
      to examine cell cycle and apoptosis. MTT assay showed a glutamate-induced
      reduction in cellular viability while treatment with C. citratus essential oil
      and F. assa-foetida extracts before, during, and after exposure to glutamate was
      increased. Flow cytometric analysis indicated that F. assa-foetida extracts
      treatment significantly (p < 0.001) attenuated glutamate-induced
      apoptotic/necrotic cell death and the necrotic rate was decreased by C. citratus
      essential oil treatment compared to glutamate group, significantly (p < 0.001).
      The results show that C. citratus essential oil and F. assa-foetida extracts
      display neuroprotective effects in glutamate-induced neurotoxicity. These
      extracts exert antiapoptotic activity in cerebellar granule neurons due to cell
      cycle arrest in G0G1 phase, which explain the beneficial effects of C. citratus
      essential oil and F. assa-foetida extracts as therapies for neurologic disorders.

PMID- 23949775
TI  - Myelination and node of Ranvier formation on sensory neurons in a defined in
      vitro system.
AB  - One of the most important developmental modifications of the nervous system is
      Schwann cell myelination of axons. Schwann cells ensheath axons to create myelin
      segments to provide protection to the axon as well as increase the conduction of
      action potentials. In vitro neuronal systems provide a unique modality to study a
      variety of factors influencing myelination as well as diseases associated with
      myelin sheath degradation. This work details the development of a patterned in
      vitro myelinating dorsal root ganglion culture. This defined system utilized a
      serum-free medium in combination with a patterned substrate, utilizing the
      cytophobic and cytophilic molecules (poly)ethylene glycol (PEG) and N-1[3
      (trimethoxysilyl) propyl] diethylenetriamine (DETA), respectively. Directional
      outgrowth of the neurites and subsequent myelination was controlled by surface
      modifications, and conformity to the pattern was measured over the duration of
      the experiments. The myelinated segments and nodal proteins were visualized and
      quantified using confocal microscopy. This tissue-engineered system provides a
      highly controlled, reproducible model for studying Schwann cell interactions with
      sensory neurons, as well as the myelination process, and its effect on neuronal
      plasticity and peripheral nerve regeneration. It is also compatible for use in
      bio-hybrid constructs to reproduce the stretch reflex arc on a chip because the
      media combination used is the same that we have used previously for motoneurons,
      muscle, and for neuromuscular junction (NMJ) formation. This work could have
      application for the study of demyelinating diseases such as diabetes induced
      peripheral neuropathy and could rapidly translate to a role in the discovery of
      drugs promoting enhanced peripheral nervous system (PNS) remyelination. 

PMID- 23949777
TI  - Forced expression of indoleamine-2,3-dioxygenase in human umbilical cord-derived
      mesenchymal stem cells abolishes their anti-apoptotic effect on leukemia cell
      lines in vitro.
AB  - The ability of mesenchymal stem cells (MSCs) to preserve cancer cells potentially
      constitutes the adverse effect of MSC-based cell therapy in the context of
      hematologic malignancy. In an effort to reverse this undesirable feature of MSCs,
      we manipulated human umbilical cord-derived MSCs (UC-MSCs) to express indoleamine
      2,3-dioxygenase (IDO), an enzyme that induces immune suppression by inhibiting T
      cell proliferation and triggering apoptosis in immune cells. Cultures of human UC
      MSCs were generated by plastic adherence method. Full-length cDNA of human IDO
      was cloned into adenovirus shuttle vector. Then, the recombinant virus harboring
      IDO gene was produced in 293 cells and used to infect UC-MSCs. Expression of IDO
      protein was detected within infected UC-MSCs, and accumulation of kynurenine was
      observed in the supernatant. Two human leukemia cell lines, Jurkat and HL-60,
      were cultured on the monolayer of native or infected UC-MSCs, respectively. It
      was observed that forced IDO expression abolished the anti-apoptotic effect of UC
      MSCs on these leukemia cells and enhanced their proliferation inhibitory effect
      on activated human lymphocytes as well as leukemia cells. These results suggested
      that equipping MSCs with IDO could be one of the reasonable strategies to reverse
      their cancer-supportive effect unfavorable for clinical applications. 

PMID- 23949778
TI  - Fatty acid composition in fetal, neonatal, and cultured cardiomyocytes in rats.
AB  - Reconstructed myocardial tissue still does not have enough pulsatile contraction.
      It is well known that fetal and mature neonatal cardiomyocytes utilize glucose
      and lipid, respectively, as their energy substrates, and that cultured ones
      mainly use glucose in spite of their age comparable to neonate ones, probably due
      to insufficient supply of lipids from culture medium. In the present study, we
      compared 7 saturated, 6 monounsaturated, and 11 polyunsaturated fatty acid
      contents in cultured cardiomyocytes (Cul group) with those in fetal (Fet group,
      approximately 17 d after impregnation) and neonatal (Neo group, 9 d old) rats,
      where the age of the Cul cells were set nearly equal to the Neo ones. Saturated
      fatty acid contents in the Cul group were generally lower than those in the Fet
      group and were close to those in the Neo group, except for C12:0 of which content
      was highest in the Neo group. Monounsaturated fatty acid contents in the Cul
      group were generally lower than those in the Fet group but similar to or higher
      than those in the Neo group, except for C24:1n-9 of which content was again
      highest in the Neo group. In contrast, most of polyunsaturated fatty acid (PUFA)
      contents in the Cul group appeared lower than those in both the Fet and Neo
      groups, and differences in 5 of 10 detected PUFAs were significant between the
      Cul and Neo groups. The results suggest that PUFA contents in cultured
      cardiomyocytes might be insufficient to exert enough contractile ability. In
      conclusion, it could be necessary for cultured cardiomyocytes to uptake more
      lipid; PUFAs in particular.

PMID- 23949780
TI  - Quantitative PCR for glucose transporter and tristetraprolin family gene
      expression in cultured mouse adipocytes and macrophages.
AB  - Quantitative real-time PCR (qPCR) such as TaqMan and SYBR Green qPCR are widely
      used for gene expression analysis. The drawbacks of SYBR Green assay are that the
      dye binds to any double-stranded DNA which can generate false-positive signals
      and that the length of the amplicon affects the intensity of the amplification.
      Previous results demonstrate that TaqMan assay is more sensitive but generates
      lower calculated expression levels than SYBR Green assay in quantifying seven
      mRNAs in tung tree tissues. The objective of this study is to expand the analysis
      using animal cells. We compared both qPCR assays for quantifying 24 mRNAs
      including those coding for glucose transporter (Glut) and mRNA-binding protein
      tristetraprolin (TTP) in mouse 3T3-L1 adipocytes and RAW264.7 macrophages. The
      results showed that SYBR Green and TaqMan qPCR were reliable for quantitative
      gene expression in animal cells. This result was supported by validation analysis
      of Glut and TTP family gene expression. However, SYBR Green qPCR overestimated
      the expression levels in most of the genes tested. Finally, both qPCR instruments
      (Bio-Rad's CFX96 real-time system and Applied Biosystems' Prism 7700 real-time
      PCR instrument) generated similar gene expression profiles in the mouse cells.
      These results support the conclusion that both qPCR assays (TaqMan and SYBR Green
      qPCR) and both qPCR instruments (Bio-Rad's CFX96 real-time system and Applied
      Biosystems' Prism 7700 real-time PCR instrument) are reliable for quantitative
      gene expression analyses in animal cells but SYBR Green qPCR generally
      overestimates gene expression levels than TaqMan qPCR. 

PMID- 23949779
TI  - Suppressive effects of fructus of Magnolia denudata on IL-4 and IL-13 expression
      in T cells.
AB  - Magnolia species have been used for the treatment of allergic diseases in Asia as
      folk medicine; however, the cellular and molecular mechanisms of its anti
      allergic effects have rarely been investigated. In this study, we demonstrated
      that a methanolic extract of the fructus of Magnolia denudata has suppressive
      effects on Th2 cytokine production such as IL-4 and IL-13, but not IFN-gamma and
      IL-17, produced by both phorbol 12-myristate 13-acetate/ionomycin (PI)- and
      CD3/CD28-stimulated EL-4 T cells. Moreover, the mRNA expression of Th2 cytokines
      was significantly inhibited, and luciferase activity in cells transiently
      transfected with IL-4 or IL-13 promoter reporter plasmids was suppressed by M.
      denudata, indicating that M. denudata may regulate these expression at the
      transcriptional level. Western blot analysis for transcription factors involved
      in the cytokine gene expression indicated that the activation of c-Jun was
      significantly downregulated in the nucleus of cells, while the activations of
      nuclear factor of activated T cells, nuclear factor kappa B and c-Fos, were not
      affected. Furthermore, the mRNA expression and nuclear translocation of GATA
      binding protein 3, a key transcriptional factor for Th2 commitment and Th2
      cytokine expression, but not T-bet and RORgammat, were dramatically downregulated
      by M. denudata. Treatment with M. denudata suppressed the phosphorylation of p38
      mitogen-activated protein kinase; however, the PI-induced phosphorylation of
      extracellular signal-related kinase and c-Jun N-terminal kinase was unaffected.
      Taken together, our study indicated that M. denudata inhibited IL-4 and IL-13
      expression, possibly through regulation of p38 mitogen-activated protein kinase
      phosphorylation and selective transcription factors, such as GATA-3 and c-Jun, in
      EL-4 T cells. 

PMID- 23949781
TI  - Responses of macrophages against Salmonella infection compared with phagocytosis.
AB  - To explore the responses of host cell after infection with live Salmonella
      compared with phagocytosis to dead bacteria, the responses of mouse macrophage
      after infection with Salmonella enteritidis C50041 and the fixed C50041 (C50041
      d) were analyzed. Results indicated that the cytotoxicity induced by C50041 was
      stronger than C50041-d. Similar changing trends of mitochondrial membrane
      potential, intracellular concentration of calcium ions, reactive oxygen species
      and nitric oxide were found between C50041 and C50041-d infection. But the cell
      responses against C50041 were earlier and stronger than C50041-d. LC3 expression
      of macrophage induced by C50041 was lower than C50041-d. C50041 significantly
      inhibited the production of tumor necrosis factor and interleukin (IL)-6. Whereas
      intracellular caspase-1 activation and IL-1beta release induced by C50041 were
      stronger than C50041-d, caspase-1 activation and IL-1beta release are the innate
      defense responses of macrophage. Therefore, it will be beneficial to explore the
      use of this pathway in the control of Salmonella infection. 

PMID- 23949782
TI  - Effects of vitamin C on characteristics retaining of in vitro-cultured mouse
      adipose-derived stem cells.
AB  - Adipose-derived stem cells (ADSCs), a subset of mesenchymal stem cells, have
      promising potential for regenerative medicine applications. However, the
      efficient culture of mouse adipose-derived stem cells (mADSCs) is complicated or
      impracticable and many properties of mADSCs are still unknown. Here, we report
      that vitamin C (Vc) is available for the long-term culture of mADSCs in vitro.
      Compared with that cultured without Vc, mADSCs growing in Vc-added media
      proliferate faster. The occurrence of replicative senescence and transformation
      of Vc-treated mADSCs is also postponed. Vc also enhanced the secretory activity
      of collagen and adipogenic differentiation ability of mADSCs. Moreover, the
      expression of CD44, Sca-1, and CD105 is higher in Vc-treated mADSCs than
      nontreated ones. We also found that genes related to proliferation, secretion,
      and pluripotency are all promoted in Vc-treated mADSCs. However, the adipogenesis
      ability and expression of CD44, Sca-1, and CD105 decreased when passage increased
      from very low passages, in parallel to the downregulation of closed-related gene
      expression. Our results indicate that Vc is essential for the maintenance of
      original properties of mADSCs in vitro; additional insights into the function of
      Vc on mADSCs are provided. Furthermore, as the passage increased in six passages,
      the characteristics of mADSCs with Vc addition were also revealed. 

PMID- 23949784
TI  - Hypoxic-ischemic substantia nigra and inferior colliculus laminar necrosis.

PMID- 23949783
TI  - Heparin and penicillamine-hypotaurine-epinephrine (PHE) solution during bovine in
      vitro fertilization procedures impair the quality of spermatozoa but improve
      normal oocyte fecundation and early embryonic development.
AB  - The presence of heparin and a mixture of penicillamine, hypotaurine, and
      epinephrine (PHE) solution in the in vitro fertilization (IVF) media seem to be a
      prerequisite when bovine spermatozoa are capacitated in vitro, in order to
      stimulate sperm motility and acrosome reaction. The present study was designed to
      determine the effect of the addition of heparin and PHE during IVF on the quality
      and penetrability of spermatozoa into bovine oocytes and on subsequent embryo
      development. Sperm quality, evaluated by the integrity of plasma and acrosomal
      membranes and mitochondrial function, was diminished (P<0.05) in the presence of
      heparin and PHE. Oocyte penetration and normal pronuclear formation rates, as
      well as the percentage of zygotes presenting more than two pronuclei, was higher
      (P<0.05) in the presence of heparin and PHE. No differences were observed in
      cleavage rates between treatment and control (P>0.05). However, the developmental
      rate to the blastocyst stage was increased in the presence of heparin and PHE
      (P>0.05). The quality of embryos that reached the blastocyst stage was evaluated
      by counting the inner cell mass (ICM) and trophectoderm (TE) cell numbers and
      total number of cells; the percentage of ICM and TE cells was unaffected (P>0.05)
      in the presence of heparin and PHE (P<0.05). In conclusion, this study
      demonstrated that while the supplementation of IVF media with heparin and PHE
      solution impairs spermatozoa quality, it plays an important role in sperm
      capacitation, improving pronuclear formation, and early embryonic development.

PMID- 23949785
TI  - Molecular characterization of a duck Tembusu virus from China.
AB  - A new emerging flavivirus caused severe egg-drop in poultry and spread quickly
      across most duck-producing regions of China in 2010. Complete genome sequencing
      indicated that the virus genome is 10,989 nucleotides in length and possesses
      typical flavivirus genome organization, 5' untranslated region (UTR)-Cv-Ci-prM-M
      E-NS1-NS2A-NS2B-NS3-NS4A-2K-NS4B-NS5-3'-UTR. The long open reading frame (ORF)
      encodes 3,425 amino acids (95-10,372 nt). The 94-nucleotide 5'-UTR is of
      intermediate size and the 617-nucleotide 3'-UTR is quite long relative to those
      of other flaviviruses. The polyprotein cleavage sites, potential glycosylation
      sites, distribution of cysteine residues, and 3'-UTR secondary structure were
      characterized. Phylogenetic analysis of the polyprotein sequences indicates that
      the HN isolate is closely related to Tembusu viruses of the Ntaya virus group. 

PMID- 23949786
TI  - Impact of the segment-specific region of the 3'-untranslated region of the
      influenza A virus PB1 segment on protein expression.
AB  - The 12 and 13 terminal nucleotides in the 3'- and 5'-untranslated regions (UTRs)
      of the influenza A virus genome, respectively, are important for the
      transcription of the viral RNA and the translation of mRNA. However, the
      functions of the segment-specific regions of the UTRs are not well known. We
      utilized an enhanced green fluorescent protein (eGFP) flanked at both ends by
      different UTRs (from the eight segments of H1N1 PR8/34) as a reporter gene to
      evaluate the effects of these UTRs on protein expression in vitro. The results
      showed that the protein expression levels of NP-eGFP, NS-eGFP, and HA-eGFP were
      higher than those of the other reporters and that the protein level of PB1-eGFP
      remained at a relatively low amount 48-h post-transfection. The results revealed
      that the UTRs of all segments differently affected the protein expression levels
      and that the effect of the UTRs of PB1 segment on protein expression was
      significant. The deletion of "UAAA" and "UAAACU" motifs in the PB1-3'-UTR
      significantly increased the protein expression level by 49.8 and 142.6%,
      respectively. This finding suggests that the "UAAACU" motif in the PB1-3'-UTR is
      at least partly responsible for the low protein expression level. By introducing
      the "UAAACU" motif into other 3'-UTRs (PA, NS, NP, and HA) at similar locations,
      the eGFP expression was reduced as expected by 56, 61, 22, and 22%, respectively.
      This result further confirmed that the "UAAACU" motif of the PB1-3'-UTR can
      inhibit protein expression. Our findings suggest that the segment-specific
      regions in the UTRs and not just the conserved regions of the UTRs play an
      important role in the viral protein expression. Additionally, the reported
      findings may also shed light on novel regulatory mechanism for the influenza A
      virus genome.

PMID- 23949787
TI  - Chemoenzymatic synthesis of immunogenic meningococcal group C polysialic acid
      tetanus Hc fragment glycoconjugates.
AB  - Vaccination with meningococcal glycoconjugate vaccines has decreased the
      incidence of invasive meningitis worldwide. These vaccines contain purified
      capsular polysaccharides attached to a carrier protein. Because of derivatization
      chemistries used in the process, conjugation of polysaccharide to protein often
      results in heterogeneous mixtures. Well-defined vaccines are needed to determine
      the relationship between vaccine structure and generated immune response. Here,
      we describe efforts to produce well-defined vaccine candidates by chemoenzymatic
      synthesis. Chemically synthesized lactosides were substrates for recombinant
      sialyltransferase enzymes from Camplyobacter jejuni and Neisseria meningitidis
      serogroup C. These resulting oligosialic acids have the same alpha(2-9) sialic
      acid repeat structure as Neisseria polysaccharide capsule with the addition of a
      conjugatable azide aglycon. The degree of polymerization (DP) of carbohydrate
      products was controlled by inclusion of the inhibitor CMP-9-deoxy-NeuNAc.
      Polymers with estimated DP < 47 (median DP 25) and DP < 100 (median DP 51) were
      produced. The receptor binding domain of the tetanus toxin protein (TetHc) was
      coupled as a carrier to the enzymatically synthesized oligosialic acids.
      Recombinant TetHc was derivatized with an alkyne squarate. Protein modification
      sites were determined by trypsin proteolysis followed by LC/MS-MS(E) analysis of
      peptides. Oligosialic acid azides were conjugated to modified TetHc via click
      chemistry. These chemoenzymatically prepared glycoconjugates were reactive in
      immunoassays with specific antibodies against either group C polysaccharide or
      TetHc. Sera of mice immunized with oligosialic acid-TetHc glycoconjugates
      contained much greater levels of polysaccharide-reactive IgG than the sera of
      control mice receiving unconjugated oligosialic acids. There was no apparent
      difference between glycoconjugates containing oligosaccharides of DP < 47 and DP
      < 100. These results suggest that chemoenzymatic synthesis may provide a viable
      method for making defined meningococcal vaccine candidates.

PMID- 23949788
TI  - Effect of a single, open-sea, air scuba dive on human micro- and macrovascular
      function.
AB  - PURPOSE: Previous studies have shown that bubble formation induced endothelial
      damage on conduit arteries. We aim to evaluate the effect of diving on
      microvascular and macrovascular function. METHODS: Nine divers took part in a
      SCUBA dive at 30 msw (400 kPa), for 30 min of bottom time. Pre- and post-dive,
      they underwent an assessment of endothelial-dependent (acetylcholine) and
      endothelial-independent (sodium nitroprusside) microvascular function (laser
      Doppler flowmetry), as well as endothelial-dependent (flow-mediated dilation) and
      endothelial-independent (nitroglycerin-mediated dilation) function. Bubble grades
      were monitored with Doppler according to the Spencer grade. RESULTS: The mean
      KISS bubble score ranged from 21.10 +/- 4.7 at rest to 55.03 +/- 8.8 after knee
      flexion. The increase in cutaneous vascular conductance elicited by either
      acetylcholine (25.34 +/- 6.71 to 7.63 +/- 1.25 %, p = 0.021) or sodium
      nitroprusside (35.24 +/- 8.75 to 7.61 +/- 1.86 %, p = 0.017) was significantly
      reduced after diving. Similarly, both flow-mediated dilation (10.8 +/- 0.9 to 5.4
      +/- 1.5 %, p = 0.002) and nitroglycerin-mediated dilation (15 +/- 1.1 to 6.5 +/-
      1.6 %, p = 0.002) were also significantly decreased. There were no correlations
      between vascular parameters and bubble formation. CONCLUSIONS: There appears to
      be a reduction in endothelium-dependent and endothelium-independent, macro- and
      microvascular function associated with diving. Our results suggest that in the
      process of vascular dysfunction during diving, functional changes in the vessel
      wall may not be limited to the endothelium and may be mediated by alterations in
      vascular smooth muscle.

PMID- 23949789
TI  - Inhomogeneous architectural changes of the quadriceps femoris induced by
      resistance training.
AB  - PURPOSE: This study aimed to clarify whether resistance training-induced changes
      in muscle architecture are homogeneous among the quadriceps and over different
      regions within each muscle. METHODS: Eleven recreationally active men (27 +/- 2
      years) completed a 12-week resistance training program for knee extensors. Before
      and after the intervention, muscle thicknesses, fascicle lengths, and pennation
      angles of the four muscles (vastus lateralis, vastus medialis, vastus
      intermedius, rectus femoris) in several regions (2-4 regions per each muscle)
      were measured using ultrasonography. Anatomical cross-sectional areas (ACSAs) at
      the same positions as the ultrasound measurements were determined from magnetic
      resonance images. RESULTS: Relative increases in the ACSA, muscle thickness, and
      pennation angle of the rectus femoris were significantly greater than those of
      the vasti. Relative increases in the ACSAs of the vastus lateralis and rectus
      femoris were significantly greater in the distal than in the proximal region, and
      those in the muscle thickness and pennation angle of the vastus intermedius were
      significantly greater in the medial than in the lateral region. Fascicle lengths
      did not change in any muscles. The interrelations between muscle thickness and
      pennation angle remained unchanged after the intervention, with a significant
      association between the relative changes of the two variables. CONCLUSION: The
      current results indicate that (1) hypertrophy of the quadriceps femoris is
      associated with a proportional increase in pennation angle but not necessarily in
      fascicle length, and (2) training-induced changes in muscle size and pennation do
      not evenly occur among the quadriceps, along or across a muscle.

PMID- 23949790
TI  - Effects of step duration in incremental ramp protocols on peak power and maximal
      oxygen consumption.
AB  - PURPOSE: Morton (J Sport Sci 29:307-309, 2011) proposed a model of the peak power
      attained in ramp protocol ([Formula: see text]) that included critical power (CP)
      and anaerobic capacity as constants, and mean ramp slope (S) as variable. Our
      hypothesis is that [Formula: see text] depends only on S, so that Morton's model
      should be applicable in all types of ramps. The aim of this study was to test
      this hypothesis by validating Morton's model using stepwise ramp tests with
      invariant step increment and increasing step duration. METHODS: Sixteen men
      performed six ramp tests with 25 W increments. Step duration was: 15, 30, 60, 90,
      120 and 180 s. Maximal oxygen consumption ([Formula: see text]) and [Formula: see
      text] were identified as the highest values reached during each test. An Astrand
      type test was also performed. We measured oxygen consumption and ventilatory
      variables, together with lactate and heart rate. RESULTS: [Formula: see text] was
      the same in all tests; [Formula: see text] was significantly lower the longer the
      step duration, and all values differed from the maximal power of the Astrand-type
      test ([Formula: see text]). Morton's model yielded an excellent fitting, with
      mean CP equal to 198.08 +/- 37.46 W and anaerobic capacity equal to 16.82 +/-
      5.69 kJ. CONCLUSIONS: Morton's model is a good descriptor of the mechanics of
      ramp tests. Further developments of Morton's model demonstrated that, whereas
      [Formula: see text] is a protocol-dependent variable, the difference between
      [Formula: see text] and CP is a constant, so that their values do not depend on
      the protocol applied.

PMID- 23949791
TI  - Alarming incidence of genital mycoplasmas among HIV-1-infected MSM in Jiangsu,
      China.
AB  - Males who have sex with men (MSM) are considered at high risk of blood-borne and
      sexually transmitted infections (STIs), mainly due to the practice of unsafe sex,
      often combined with drug use and needle-sharing. A cross-sectional study was
      designed for the detection of genital mycoplasmas during the period from March
      2009 to May 2010 in Jiangsu province. This work was approved by the Research
      ethics Committee of Jiangsu Centers for Diseases Prevention and Control (CDC),
      and written consent was obtained from all participants. In total, 243 human
      immunodeficiency virus-1 (HIV-1)-infected MSM were screened in this study. Over
      half of them reported a history of sexual activity with females (65.0 %), and
      26.3 % reported a history of sexually transmitted diseases (STDs) other than HIV.
      44.0 % of patients were in the first 2 years of their HIV infection, and 72.4 %
      were still in HIV progression. Of the 243 analyzed samples, all were positive for
      at least one kind of mycoplasma. The infection rates of Mycoplasma genitalium, M.
      fermentans, M. penetrans, and M. pirum were 25.5, 9.9, 2.5, and 18.5 %,
      respectively. The M. genitalium infection was associated with a history of sexual
      activity with females, and those who had sex with females showed higher infection
      rates. Six  M. penetrans-positive patients were still in HIV infection
      progression and did not receive highly active antiretroviral therapy (HAART). Men
      who perform this particular behavior are at higher risk of Mycoplasma infections.
      Further molecular and epidemiological cohort studies with larger populations are
      needed in order to identify the role of Mycoplasma infections in HIV-1-infected
      MSM.

PMID- 23949792
TI  - Treatment of anthracycline extravasations using dexrazoxane.
AB  - Extravasation of cytotoxic agents is a true medical emergency. Dexrazoxane is the
      only licensed drug for the treatment of anthracycline extravasations. Dexrazoxane
      proved to be effective and moderately well tolerated. However, alternative
      approaches for the management of anthracycline extravasations are available such
      as topical DMSO and cooling. There appears to be general agreement about
      dexrazoxane usefulness when extravasations involve large volumes of anthracycline
      and/or central venous access device. Nevertheless, the non-invasive combination
      of DMSO and cooling is the most commonly described therapy, particularly in small
      anthracycline extravasations. Further research is still needed to establish
      unequivocal situations where dexrazoxane must be initiated. 

PMID- 23949793
TI  - Effects of clinoptilolite on growth performance and antioxidant status in
      broilers.
AB  - The objective of this study was to compare the effects of natural clinoptilolite
      and modified clinoptilolite on growth performance and antioxidant capacity in
      broiler chicks. Two hundred forty 1-day-old commercial Arbor Acres broilers were
      randomly distributed into three treatments, each of which had eight replicates.
      Each replicate contains 10 chicks. Control (CON) group fed with the basal diets,
      natural clinoptilolite (NCLI) group fed basal diets with 2 % natural
      clinoptilolite, and modified clinoptilolite (MCLI) group fed basal diets with 2 %
      modified clinoptilolite for 42 days. The results showed that the 2 %
      supplementation of natural clinoptilolite and modified clinoptilolite had no
      adverse effect on growth performance of broilers at 42 days of age. Relative
      weights of organs were not influenced by dietary treatments at 21 and 42 days.
      The activity of total nitric oxide synthase was significantly (P < 0.05)
      decreased in MCLI group than CON group at 21 days of age. At 21 and 42 days, the
      activities of glutathione peroxidase, catalase, total superoxide dismutase, total
      antioxidant capacity (T-AOC) were significantly (P < 0.05) increased in NCLI and
      MCLI groups than the CON group while there was no difference in T-AOC between CON
      and NCLI groups. The malondialdehyde content was significantly (P < 0.05)
      decreased in NCLI and MCLI groups than the CON group. It was concluded that the
      addition of 2 % natural clinoptilolite and modified clinoptilolite to diet can
      improve antioxidant capacity in broilers, although their effects on growth
      performance was negligible.

PMID- 23949794
TI  - Slanted spiral microfluidics for the ultra-fast, label-free isolation of
      circulating tumor cells.
AB  - The enumeration and characterization of circulating tumor cells (CTCs), found in
      the peripheral blood of cancer patients, provide a potentially accessible source
      for cancer diagnosis and prognosis. This work reports on a novel spiral
      microfluidic device with a trapezoidal cross-section for ultra-fast, label-free
      enrichment of CTCs from clinically relevant blood volumes. The technique utilizes
      the inherent Dean vortex flows present in curvilinear microchannels under
      continuous flow, along with inertial lift forces which focus larger CTCs against
      the inner wall. Using a trapezoidal cross-section as opposed to a traditional
      rectangular cross-section, the position of the Dean vortex core can be altered to
      achieve separation. Smaller hematologic components are trapped in the Dean
      vortices skewed towards the outer channel walls and eventually removed at the
      outer outlet, while the larger CTCs equilibrate near the inner channel wall and
      are collected from the inner outlet. By using a single spiral microchannel with
      one inlet and two outlets, we have successfully isolated and recovered more than
      80% of the tested cancer cell line cells (MCF-7, T24 and MDA-MB-231) spiked in
      7.5 mL of blood within 8 min with extremely high purity (400-680 WBCs mL(-1); ~4
      log depletion of WBCs). Putative CTCs were detected and isolated from 100% of the
      patient samples (n = 10) with advanced stage metastatic breast and lung cancer
      using standard biomarkers (CK, CD45 and DAPI) with the frequencies ranging from 3
      125 CTCs mL(-1). We expect this simple and elegant approach can surmount the
      shortcomings of traditional affinity-based CTC isolation techniques as well as
      enable fundamental studies on CTCs to guide treatment and enhance patient care.

PMID- 23949795
TI  - IL-2/anti-IL-2 complex: a novel strategy of in vivo regulatory T cell expansion
      in renal injury.

PMID- 23949796
TI  - Metabolomics reveals signature of mitochondrial dysfunction in diabetic kidney
      disease.
AB  - Diabetic kidney disease is the leading cause of ESRD, but few biomarkers of
      diabetic kidney disease are available. This study used gas chromatography-mass
      spectrometry to quantify 94 urine metabolites in screening and validation cohorts
      of patients with diabetes mellitus (DM) and CKD(DM+CKD), in patients with DM
      without CKD (DM-CKD), and in healthy controls. Compared with levels in healthy
      controls, 13 metabolites were significantly reduced in the DM+CKD cohorts
      (P<=0.001), and 12 of the 13 remained significant when compared with the DM-CKD
      cohort. Many of the differentially expressed metabolites were water-soluble
      organic anions. Notably, organic anion transporter-1 (OAT1) knockout mice
      expressed a similar pattern of reduced levels of urinary organic acids, and human
      kidney tissue from patients with diabetic nephropathy demonstrated lower gene
      expression of OAT1 and OAT3. Analysis of bioinformatics data indicated that 12 of
      the 13 differentially expressed metabolites are linked to mitochondrial
      metabolism and suggested global suppression of mitochondrial activity in diabetic
      kidney disease. Supporting this analysis, human diabetic kidney sections
      expressed less mitochondrial protein, urine exosomes from patients with diabetes
      and CKD had less mitochondrial DNA, and kidney tissues from patients with
      diabetic kidney disease had lower gene expression of PGC1alpha (a master
      regulator of mitochondrial biogenesis). We conclude that urine metabolomics is a
      reliable source for biomarkers of diabetic complications, and our data suggest
      that renal organic ion transport and mitochondrial function are dysregulated in
      diabetic kidney disease. 

PMID- 23949797
TI  - Human kidney cell reprogramming: applications for disease modeling and
      personalized medicine.
AB  - The ability to reprogram fully differentiated cells into a pluripotent embryonic
      state, termed induced pluripotent stem cells (iPSCs), has been met with great
      excitement. iPSC technology has advanced the fundamental study of disease
      modeling with the potential for cell-replacement therapy, especially in the
      neuronal and cardiac fields. However, renal medicine as of yet has not benefited
      from similar advancements. This review summarizes the unique characteristics of
      iPSCs and their potential applications for modeling kidney disease. Pioneering
      such endeavors could yield constructs that recapitulate disease phenotypes, open
      avenues for more targeted drug development, and potentially serve as
      replenishable sources for replacement of kidney cells in the setting of human
      disease.

PMID- 23949798
TI  - Proteinuria impairs podocyte regeneration by sequestering retinoic acid.
AB  - In CKD, the risk of kidney failure and death depends on the severity of
      proteinuria, which correlates with the extent of podocyte loss and glomerular
      scarring. We investigated whether proteinuria contributes directly to progressive
      glomerulosclerosis through the suppression of podocyte regeneration and found
      that individual components of proteinuria exert distinct effects on renal
      progenitor survival and differentiation toward a podocyte lineage. In particular,
      albumin prevented podocyte differentiation from human renal progenitors in vitro
      by sequestering retinoic acid, thus impairing retinoic acid response element
      (RARE)-mediated transcription of podocyte-specific genes. In mice with Adriamycin
      nephropathy, a model of human FSGS, blocking endogenous retinoic acid synthesis
      increased proteinuria and exacerbated glomerulosclerosis. This effect was related
      to a reduction in podocyte number, as validated through genetic podocyte labeling
      in NPHS2.Cre;mT/mG transgenic mice. In RARE-lacZ transgenic mice, albuminuria
      reduced retinoic acid bioavailability and impaired RARE activation in renal
      progenitors, inhibiting their differentiation into podocytes. Treatment with
      retinoic acid restored RARE activity and induced the expression of podocyte
      markers in renal progenitors, decreasing proteinuria and increasing podocyte
      number, as demonstrated in serial biopsy specimens. These results suggest that
      albumin loss through the damaged filtration barrier impairs podocyte regeneration
      by sequestering retinoic acid and promotes the generation of FSGS lesions. Our
      findings may explain why reducing proteinuria delays CKD progression and provide
      a biologic rationale for the clinical use of pharmacologic modulators to induce
      regression of glomerular diseases. 

PMID- 23949799
TI  - The predictive value of kidney allograft baseline biopsies for long-term graft
      survival.
AB  - The effect of baseline histology and individual histologic lesions at the time of
      transplantation on long-term graft survival has been evaluated using different
      scoring systems, but the predictive capacity of these systems has not been
      adequately validated. All kidney recipients transplanted in a single institution
      between 1991 and 2009 who underwent a baseline kidney allograft biopsy at
      transplantation were included in this prospective study (N=548). All baseline
      biopsies were rescored according to the updated Banff classification, and the
      relationship between the individual histologic lesions and donor demographics was
      assessed using hierarchical clustering and principal component analysis. Survival
      analysis was performed using Cox proportional hazards analysis and log-rank
      testing. Mean follow-up time was 6.7 years after transplantation. Interstitial
      fibrosis, tubular atrophy, and glomerulosclerosis associated significantly with
      death-censored graft survival, whereas arteriolar hyalinosis and vascular intimal
      thickening did not. Notably, donor age correlated significantly with interstitial
      fibrosis, tubular atrophy, and glomerulosclerosis and associated independently
      with graft survival. On the basis of these findings, a novel scoring system for
      prediction of 5-year graft survival was constructed by logistic regression
      analysis. Although the predictive performance of previously published histologic
      scoring systems was insufficient to guide kidney allocation in our cohort
      (receiver operating characteristic area under the curve <=0.62 for each system),
      the new system based on histologic data and donor age was satisfactory for
      prediction of allograft loss (receiver operating characteristic area under the
      curve = 0.81) and may be valuable in the assessment of kidney quality before
      transplantation. 

PMID- 23949800
TI  - Survivin mediates renal proximal tubule recovery from AKI.
AB  - AKI induces the renoprotective upregulation of survivin expression in kidney
      epithelial cells, but the underlying mechanisms have not been identified. To
      determine the role of survivin in renal recovery from AKI, we generated mice with
      renal proximal tubule-specific deletion of survivin (survivin(ptKO)). Renal
      survivin expression increased substantially in response to ischemia-reperfusion
      (I/R) injury in control littermates but remained minimal in survivin(ptKO) mice.
      Functional and histologic data indicated similar degrees of renal injury in
      survivin(ptKO) and control mice 24 hours after reperfusion, but recovery was
      markedly delayed in survivin(ptKO) mice. In MCT cells, a mouse renal proximal
      tubule cell line, ATP depletion by antimycin A treatment upregulated survivin
      expression through a phospho-STAT3-dependent pathway. In wild-type mice,
      inhibition of STAT3 kinase diminished I/R-induced upregulation of STAT3
      phosphorylation and survivin expression and delayed recovery. Furthermore, I/R
      injury activated Notch-2 signaling, and a gamma-secretase inhibitor suppressed
      I/R-induced Notch-2 signaling, STAT3 phosphorylation, and survivin expression and
      delayed recovery. In MCT cells, inhibition of gamma-secretase similarly
      attenuated antimycin A-induced Notch-2 activation, upregulation of survivin, and
      phosphorylation of STAT3, but STAT3 kinase inhibition did not prevent Notch-2
      activation. Therefore, these data suggest that STAT3 phosphorylation and
      subsequent upregulation of survivin expression mediated by Notch-2 signaling in
      renal proximal tubule epithelial cells aid in the functional and structural
      recovery of the kidney from AKI. 

PMID- 23949803
TI  - Common-garden experiments reveal geographical variation in the interaction among
      Crotalaria pallida (Leguminosae: Papilionideae), Utetheisa ornatrix L.
      (Lepidoptera: Arctiidae), and extrafloral nectary visiting ants.
AB  - The study of geographical variation is a key approach to understand evolution of
      ecological interactions. We investigated geographical variation in the
      interaction among Crotalaria pallida (Leguminosae: Papilionideae), its
      specialized herbivore, Utetheisa ornatrix L. (Lepidoptera: Arctiidae), and ants
      attracted to extrafloral nectaries (EFNs). First, we used common-garden
      experiments with plants collected in different sites at different geographical
      scales to test for differences among populations in C. pallida attractiveness to
      ants. When we compared three populations from Southeast Brazil (150 km apart),
      the number of visiting ants per plant, and the percent of termite baits attacked
      by ants, were significantly different among plant populations. In a comparison of
      populations from SE Brazil and Florida (USA), there was no significant difference
      between the populations in the number of ants per plant or the frequency of baits
      attacked. Second, we tested in a common garden if U. ornatrix larvae present any
      behavior to avoid ant predation, and if there were genetic differences among
      populations. We observed that most larvae moved away from the vicinity of the
      EFNs (flowers and fruits) to the plant leaves. Of the larvae that moved to
      leaves, only 10% were attacked by ants while 89% of larvae that stayed near the
      fruit/flower were attacked. There was a significant difference among populations
      in the frequency of larvae that moved to the leaves and the frequency of larvae
      attacked by ants. We discuss the possible causes of the geographical differences
      observed and propose future research directions in this system. 

PMID- 23949801
TI  - Randomized, controlled trial of glucose-sparing peritoneal dialysis in diabetic
      patients.
AB  - Glucose-containing peritoneal dialysis solutions may exacerbate metabolic
      abnormalities and increase cardiovascular risk in diabetic patients. Here, we
      examined whether a low-glucose regimen improves metabolic control in diabetic
      patients undergoing peritoneal dialysis. Eligible patients were randomly assigned
      in a 1:1 manner to the control group (dextrose solutions only) or to the low
      glucose intervention group (IMPENDIA trial: combination of dextrose-based
      solution, icodextrin and amino acids; EDEN trial: a different dextrose-based
      solution, icodextrin and amino acids) and followed for 6 months. Combining both
      studies, 251 patients were allocated to control (n=127) or intervention (n=124)
      across 11 countries. The primary endpoint was change in glycated hemoglobin from
      baseline. Mean glycated hemoglobin at baseline was similar in both groups. In the
      intention-to-treat population, the mean glycated hemoglobin profile improved in
      the intervention group but remained unchanged in the control group (0.5%
      difference between groups; 95% confidence interval, 0.1% to 0.8%; P=0.006). Serum
      triglyceride, very-low-density lipoprotein, and apolipoprotein B levels also
      improved in the intervention group. Deaths and serious adverse events, including
      several related to extracellular fluid volume expansion, increased in the
      intervention group, however. These data suggest that a low-glucose dialysis
      regimen improves metabolic indices in diabetic patients receiving peritoneal
      dialysis but may be associated with an increased risk of extracellular fluid
      volume expansion. Thus, use of glucose-sparing regimens in peritoneal dialysis
      patients should be accompanied by close monitoring of fluid volume status. 

PMID- 23949804
TI  - Illustrated and annotated checklist of Brazilian gall morphotypes.
AB  - The analysis on nine inventories on the richness and diversity of galling
      herbivores in Brazil accounted for 806 gall systems occurring in 443 host-plant
      species from 74 plant families. This checklist of the Brazilian gall morphotypes
      proposes seven standardized morphotypes and five additional shapes that group the
      majority of the three-dimensional shapes reported in literature. Criteria are
      proposed to standardize the terminology, and a critical analysis is provided
      aiming to avoid possible inconsistencies in order to generate easily comparable
      data in future inventories. The morphotypes are herein catalogued in alphabetical
      order, accompanied by a conceptual definition, an illustration, and examples that
      best represent the shape. It is proposed that the inventories should present at
      least the (1) host-plant species, (2) galling herbivore species or its
      identification to the lowest possible taxonomic level, (3) host-plant galled
      organ and gall position, (4) gall morphotype, (5) gall color and registration of
      indumentum when present, (6) gall phenological and developmental data, (7)
      association with other trophic levels, and (8) additional information, such as
      dimension, and number of chamber(s). 

PMID- 23949802
TI  - MicroRNA-155 drives TH17 immune response and tissue injury in experimental
      crescentic GN.
AB  - CD4(+) T cells play a pivotal role in the pathogenesis of autoimmune disease,
      including human and experimental crescentic GN. Micro-RNAs (miRs) have emerged as
      important regulators of immune cell development, but the impact of miRs on the
      regulation of the CD4(+) T cell immune response remains to be fully clarified.
      Here, we report that miR-155 expression is upregulated in the kidneys of patients
      with ANCA-associated crescentic GN and a murine model of crescentic GN
      (nephrotoxic nephritis). To elucidate the potential role of miR-155 in T cell
      mediated inflammation, nephritis was induced in miR-155(-/-) and wild-type mice.
      The systemic and renal nephritogenic TH17 immune response decreased markedly in
      nephritic miR-155(-/-) mice. Consistent with this finding, miR-155-deficient mice
      developed less severe nephritis, with reduced histologic and functional injury.
      Adoptive transfer of miR-155(-/-) and wild-type CD4(+) T cells into nephritic
      recombination activating gene 1-deficient (Rag-1(-/-)) mice showed the T cell
      intrinsic importance of miR-155 for the stability of pathogenic TH17 immunity.
      These findings indicate that miR-155 drives the TH17 immune response and tissue
      injury in experimental crescentic GN and show that miR-155 is a potential
      therapeutic target in TH17-mediated diseases. 

PMID- 23949805
TI  - Andropogon bicornis (Poales, Poaceae): a hibernation site for Pentatomoidea
      (Hemiptera: Heteroptera) in a rice-growing region of Southern Brazil.
AB  - Tussocks of Andropogon bicornis (Poaceae) make up a significant part of the
      landscape of the rice-growing region of south Brazil. However, little is known
      about their role in maintaining insect diversity in anthropized regions. We
      tested the hypothesis that A. bicornis is a hibernation site for Pentatomoidea
      (Hemiptera: Heteroptera) by analyzing the composition, structure, and diversity
      of pentatomoid assemblages over the course of a year. A total of 208 tussocks
      were removed at fortnightly intervals from April 2010 to March 2011. We collected
      3,423 pentatomoid specimens belonging to 22 species distributed in 13 genera of
      three families, Pentatomidae, Scutelleridae, and Thyreocoridae. The most common
      species was Tibraca limbativentris Stal, the main rice pest in southern Brazil,
      followed by Oebalus ypsilongriseus (De Geer) and Edessa meditabunda (Fabricius).
      Abundance and species richness were the lowest in January, February, and March
      and the highest in July, August, and September. A combination of high species
      diversity observed during the colder months, including several unrelated to rice,
      and the absence of immature specimens in the tussocks strengthens the hypothesis
      that A. bicornis is a hibernation site for pentatomoids in the region. 

PMID- 23949806
TI  - Scena propylea (Druce) (Lepidoptera: Erebidae) an endemic species of Mexico.
AB  - A revision of the bibliography, as well as an analysis on the data from the
      specimen labels of Scena propylea (Druce) (Erebidae: Arctiinae: Euchromiina)
      deposited in different scientific collections, was carried out and included
      information from 1894 to 2010. Its geographical distribution is restricted to the
      Trans-Mexican Volcanic Belt which determines this species as endemic. Data are
      provided on the biogeography, ecology and biology for this species. Its food
      plant is Thenardia floribunda (Apocynaceae) which is also endemic to Mexico. From
      this analysis, we propose the inclusion of both species in the document known as
      the Norma Oficial Mexicana 059 which encompasses the environmental protection of
      wild flora and fauna species native to Mexico and their risk categories, as well
      as the specifications for their inclusion, exclusion or change and a list of all
      species at risk. 

PMID- 23949807
TI  - Xylocopa bees in tropical coastal sand dunes: use of resources and their floral
      syndromes.
AB  - Large bees such as species from Xylocopa Latreille are usually associated with
      pollination in tropical sand dune areas, which frequently present shrubby
      herbaceous vegetation adapted to conditions of high salinity, high solar
      radiation and strong winds. We report on the diversity of Xylocopa and the plants
      they visited to collect nectar and pollen, focusing on the floral syndromes they
      present in these plants and on the breadth of the trophic niche in a tropical
      sand dune fragment over the year. The field work was carried out monthly in
      Baixio (Bahia, Brazil; Northern Coast Environmental Protection Area) from April
      2008 to March 2009, over two consecutive days, from 06:30 AM to 05:00 PM. The
      medium-large body sized Xylocopa (Neoxylocopa) cearensis Ducke and Xylocopa
      (Schonnherria) subcyanea Perez were noticeable for their frequency, constancy on
      the flowers and sharing of plant species. Xylocopa spp. visited plants with
      flowers of different shapes, colors, inflorescence arrangement and syndromes.
      However, their resource collections were mainly concentrated on Cuphea brachiata,
      Waltheria cinerascens, Croton sellowii and Chamaecrista ramosa, which may be
      considered key species for Xylocopa spp. maintenance in coastal sand dune and
      restinga environments in Northeast Brazil. 

PMID- 23949808
TI  - Ants of three adjacent habitats of a transition region between the cerrado and
      caatinga biomes: the effects of heterogeneity and variation in canopy cover.
AB  - Habitat heterogeneity and complexity associated with variations in climatic
      conditions are important factors determining the structure of ant communities in
      different terrestrial ecosystems. The objective of this study was to describe the
      horizontal and vertical distribution patterns of the ant community associated
      with three adjacent habitats in a transition area between the Cerrado and
      Caatinga biomes at the Pandeiros River, state of Minas Gerais, Brazil. We tested
      the following hypotheses: (1) the richness and composition of ant species and
      functional group structure changes between different habitats and strata; (2)
      habitats with higher tree species richness and density support higher ant species
      richness; and (3) habitats with lower variation in canopy cover support higher
      ant species richness. Sampling was conducted in three adjacent habitats and at
      three vertical strata. Ant species richness was significantly different among
      vertical strata. Ant species composition was different among both habitats and
      vertical strata and functional group structure was divergent among habitats.
      Partitioning of the diversity revealed that the diversity for the three
      components was statistically different from the one expected by the null model;
      alpha and beta 2 were higher and beta 1 was lower than the values expected by
      chance. Tree density and variation in canopy cover negatively affected ant
      species richness. The occurrence of different species and the changing of
      functional group structures in different habitats and strata suggest an
      ecological-evolutionary relationship between ants and their habitats and
      emphasize the need to implement local conservation strategies in the ecotones
      between biomes. 

PMID- 23949809
TI  - Population dynamics of drosophilids in the pampa biome in response to
      temperature.
AB  - Environmental variables such as temperature and rainfall can directly affect the
      community structure of dipterans. Seasonal oscillations in the abundance of
      species of Drosophilidae reflect differences in how tolerant populations are to
      climatic conditions. Over a period of 14 months, we collected samples in two
      habitats in the Pampa biome in the municipality of Sao Luiz Gonzaga, state of Rio
      Grande do Sul, Brazil (28 degrees 24'28"S, 54 degrees 57'39"W). The influence of
      environmental variables on populations of Drosophilidae was evaluated for both
      collecting sites by using correlation analysis. The results suggested a negative
      correlation between the abundances of Drosophila cardinoides Dobzhansky & Pavan,
      Drosophila maculifrons Duda, Drosophila melanogaster Meigen, Drosophila
      nigricruria Patterson & Mainland, and Zygothrica vittimaculosa Burla with
      temperature, which is reflected in the distribution of these species within
      Brazil. Our findings are important for characterizing and preserving biodiversity
      in this almost-unknown biome in southern Brazil given the current climate change
      scenario. 

PMID- 23949810
TI  - Scanning electron microscopy studies of the antennal sensilla of Metaphycus
      parasaissetiae Zhang & Huang (Hymenoptera: Encyrtidae).
AB  - Metaphycus parasaissetiae Zhang & Huang (Hymenoptera: Encyrtidae) is an important
      adult parasitoid of Parasaissetia nigra Nietner (Hemiptera: Coccoidea). The
      external morphology of the antennal sensilla of male and female M. parasaissetiae
      was examined using scanning electron microscopy. The geniculate antennae of male
      and female M. parasaissetiae were composed of a scape with a basal radicula, a
      barrel-shaped pedicel, and a long flagellum. Twelve morphologically distinct
      types of sensilla were identified, including multiporous placoid sensilla,
      campaniform sensilla, finger-like sensilla, multiporous basiconic sensilla (BS
      1), three aporous types of basiconic sensilla (BS-2, BS-3, and BS-4), two types
      of aporous trichoid sensilla (TS-1 and TS-3), a type of multiporous trichoid
      sensilla (TS-2), and two types of sensilla chaetica (CH-1 and CH-2). Sex
      dimorphism in the sensilla composition of M. parasaissetiae is also observed.
      Major differences between the sexes were found in the number, distribution,
      shape, structure, and size of the identified sensilla. We also discuss on the
      functional aspects of these sensilla to elucidate the mechanisms involved in host
      searching and courtship behavior of M. parasaissetiae. 

PMID- 23949811
TI  - Description of the immatures of Scaptocoris carvalhoi Becker (Hemiptera:
      Cydnidae).
AB  - Nymphs and adults of the burrower bug Scaptocoris carvalhoi Becker feed on
      vegetal sap of their host plants through the roots, and little is known on the
      morphology and biology of its immature stage. Therefore, we aimed to characterize
      the immatures of S. carvalhoi by describing the egg and the morphology of each
      instar. Eggs of S. carvalhoi have a smooth chorion surface without visible
      micropylar processes. The presence of five instars was confirmed by the
      coefficient of determination (R (2) > 0.95) and by the growth constant (K between
      1.2 and 1.6). Nymphs have an elliptical body and fossorial scythe-like forelegs.
      The tarsi are absent as in adults, and the prototarsal insertion region becomes
      visible only in the fourth instar. Nymphs from first to fourth instar of S.
      carvalhoi showed the presence of 1 + 1 trichobothria in urosternites III to VII,
      close to the anterior margin and inside the spiracles; besides these
      trichobothria, fifth instars presented 1 + 1 pre-trichobothria in urosternites
      III to V located posteriorly, almost in the row of spiracles close to the
      posterior margin of the urosternites. This is the first detailed morphological
      record of immatures belonging to Scaptocoris. 

PMID- 23949812
TI  - Age and morphological changes in the Epiponini wasp Polybia paulista Von Ihering
      (Hymenoptera: Vespidae).
AB  - The division of labor is a central theme in the study of social insects. In bees
      and wasps, this activity is regulated by age polyethism. Important physiological
      and morphological changes have been widely studied in the polyethism of honeybee
      workers. In contrast, this is a relatively unexplored subject in social vespids.
      Our goal was to determine if there are detectable morphological changes in the
      body of the Epiponini wasp Polybia paulista Von Ihering or in certain glands in
      relation to age polyethism. We observed changes in the body weight, the salivary
      gland, and the mandibular gland that were associated with age, and our results
      suggest that social relationships and task performance are important to these
      changes. This contrasts with observations in Polistes and is different from the
      Apis mellifera Linnaeus age polyethism model. 

PMID- 23949813
TI  - Two new species of Wockia heinemann (Lepidoptera: Urodidae) from Jamaica.
AB  - Wockia diabolica n. sp. and Wockia tetroidon n. sp. are described from female
      specimens collected from Jamaica. Both new species are distinguished from Wockia
      chewbacca Adamski, a Mexican species, in having a pair of signa within the corpus
      bursa of the female genitalia. Photographic images are provided for the imagoes,
      and illustrations of the genitalia are included. Distributions of these new taxa
      represent the first records of Wockia from West Indies. 

PMID- 23949814
TI  - Antibiosis and non-preference of Sitobion avenae (F.) (Hemiptera: Aphididae) on
      leaves and ears of commercial cultivars of wheat (Triticum aestivum).
AB  - Little is known on the resistance of wheat cultivars to Sitobion avenae (F.) in
      Brazil. The goal of this work was to assess the behavior and biology of S. avenae
      on four commercial wheat cultivars to verify the existence of resistance by
      antibiosis in leaves and ears and non-preference in the ears. The smallest net
      fecundity rates of S. avenae in wheat leaves have been found in the cultivars
      Embrapa 22 and BRS264, which did not differ between themselves. The intrinsic
      rate of increase of S. avenae was smaller in leaves of Embrapa 22 than in
      cultivars BRS254 and BRS Timbauva. The smallest net fecundity rates of S. avenae
      in wheat ears were observed in the cultivars BRS254 and Embrapa 22. The intrinsic
      rate of increase of the aphid in the ear of cultivar Embrapa 22 was smaller than
      in BRS Timbauva and BRS264, but did not differ from BRS254. The organ of the
      wheat plant in which the aphid was reared influences antibiosis resistance, but
      the cultivar BRS Timbauva was considered susceptible and Embrapa 22 resistant to
      S. avenae in both plant organs tested. Ears of wheat cultivars tested did not
      show differences in the mechanism of resistance by non-preference to S. avenae. 

PMID- 23949815
TI  - Dynamics and characterization of Aedes aegypti (L.) (Diptera: Culicidae) key
      breeding sites.
AB  - The present study aimed to analyze the dynamics of containers used as breeding
      sites by Aedes aegypti (L.) in the city of Aracaju, SE, one of the Northeast
      Brazilian states. A total of three entomological surveys were performed during
      different precipitation levels. Breeding sites were categorized according to
      their function into storage, disposable containers, and reusable containers.
      "Mean number of pupae" and "frequency of each type of breeding site" were the
      criteria considered to identify key breeding sites. House index and Breteau index
      were calculated in each survey. A total of 3,647 water reservoirs were found, of
      which 220 were breeding sites, where 22,880 immature forms were identified. There
      were no differences in the mean number of larvae of several types of breeding
      sites and in the number of larvae among surveys. Larval indices showed a
      reduction in the second visit, but with no effect on adult occurrence when the
      number of pupae was considered. Key breeding sites resulted from containers used
      for water storage. The area studied showed conditions favorable to a new epidemic
      of dengue fever. 

PMID- 23949816
TI  - Triatoma dimidiata (Latreille) abundance and infection with Trypanosoma cruzi in
      a rural community of Yucatan, Mexico.
AB  - The present is a longitudinal study that describes the abundance of Triatoma
      dimidiata (Latreille) (Hemiptera: Reduviidae) and its infection with Trypanosoma
      cruzi in a rural community of Yucatan, Mexico. From a total of 370 individuals
      collected, 81.3% were adults, most from intradomicile ecotope (282/301), but
      nymphs were more abundant in peridomicile (58/69). The overall proportion of
      infected bugs was 21.9% (23.9% of adults and 13% of nymphs). The infection
      proportion was similar between intradomicile and peridomicile ecotopes (22.8% and
      18.1%, respectively). Overall, 76.5% (36/47) of the houses and their backyards
      were infested. Of those, 27.7% were colonized and 75% had infected triatomines.
      Our data showed different proportions on infestation, colonization and bug
      density. Ninety-seven percent of overall peridomicile abundance was distributed
      in chicken coops, doghouses, opossum nests and dove cages. Triatomine
      entomological indices showed higher infestation and density inside domiciles, but
      higher colonization in the peridomicile. The abundance, the amount of infected
      intradomicile adult T. dimidiata and the incidence of infestation showed a
      seasonal pattern, with 63.7% of all individuals collected during the late dry
      season (April to June). We showed the peridomicile colonization of animal
      shelters and suggest it as a relevant source of T. dimidiata individuals. As
      infected bugs were found in both ecotopes, the studied area is under a high risk
      of T. cruzi transmission to humans. 

PMID- 23949817
TI  - On the presence of five species of naupactini (Coleoptera: Curculionidae)
      damaging soybean in Brazil.
AB  - We report five broad-nosed weevils of the tribe Naupactini, Naupactus leucoloma
      Boheman, Naupactus minor (Buchanan), Naupactus peregrinus (Buchanan), Naupactus
      tremolerasi Hustache and Pantomorus viridisquamosus (Boheman) (Coleoptera:
      Curculionidae) damaging soybean plants in the state of Rio Grande do Sul, Brazil.
      Some of these species are recorded for the first time in Brazil, and they all
      belong to species groups naturally distributed in the prairies of southern
      Brazil, Uruguay, Central Argentina and Paraguay. Three of them have been
      introduced, established and expanded in other countries outside South America.
      The five species in conjunction with other native species of Naupactini could
      cause severe damages to soybean crops if the root-feeding larvae attack young
      growing plants. 

PMID- 23949818
TI  - Technique for restoration of mite (Acari) preparations in deteriorated Hoyer's
      medium.
AB  - The Acari Collection of Instituto Butantan (IBSP), Sao Paulo, Brazil, includes
      many types and other identified mite specimens that were mounted in Hoyer's
      medium, mainly in the first part of last century. An effort to restore degraded
      preparations was initiated in 1996. In this process, an improved technique was
      developed, allowing the adequate cleaning of specimens mounted up to 50-70 years
      before. Types and other identified specimens of Trombidiformes (Harpirhynchidae
      and Trombiculidae), Sarcoptiformes (Acaridae, Atopomelidae, Listrophoridae, and
      Psoroptidae) and Mesostigmata (Dermanyssidae, Ixodorhynchidae, Laelapidae,
      Macronyssidae, and Spinturnicidae) deposited at IBSP Collection have been
      satisfactorily restored. 

PMID- 23949819
TI  - Osteogenesis imperfecta, tricho-dento-osseous syndrome and intellectual
      disability: a familial case with 17q21.33-q22 (COL1A1 and DLX3) deletion and
      7q32.3-q33 duplication resulting from a reciprocal interchromosomal insertion.
AB  - We report on a 22-year-old woman with features of osteogenesis imperfecta (OI),
      tricho-dento-osseous (TDO) syndrome and intellectual disability. Whole genome
      oligonucleotide microarray analysis revealed a copy number gain of 3 Mb in 7q32.3
      q33 and a loss of 3.4 Mb in 17q21.33-q22. FISH analysis showed that the third
      copy of 7q32 was inserted into the long arm of one chromosome 17, exactly in the
      region 17q21.33-q22 that was deleted. The maternal uncle presented with clinical
      features similar to the proposita and had the same chromosomal anomalies. The
      mother of the proposita and two other family members were balanced carriers of
      this rearrangement, interpreted as an interchromosomal reciprocal insertion.
      Reciprocal insertion/four-break rearrangement is a very rare chromosomal event.
      The deleted region on chromosome 17 contains 39 genes, including COL1A1 and DLX3
      involved in OI and TDO syndrome respectively. The CACNA1G gene on the deleted
      segment of chromosome 17 may be a good candidate gene to explain the intellectual
      impairment. (c) 2013 Wiley Periodicals, Inc. 

PMID- 23949820
TI  - Halorubrum rubrum sp. nov., an extremely halophilic archaeon from a Chinese salt
      lake.
AB  - Two halophilic archaeal strains, YC87(T) and YCA11, were isolated from Yuncheng
      salt lake in Shanxi, China. Cells of the two strains were observed to be
      pleomorphic rod-shaped, stained Gram-negative and produced red-pigmented
      colonies. Strain YC87(T) was able to grow at 20-50  degrees C (optimum 37 
      degrees C), at 1.4-4.8 M NaCl (optimum 2.1 M NaCl), at 0.05-1.0 M MgCl2 (optimum
      0.3 M MgCl2) and at pH 6.0-9.0 (optimum pH 7.0) while strain YCA11 was able to
      grow at 20-50  degrees C (optimum 37  degrees C), at 2.1-4.8 M NaCl (optimum 3.1
      M NaCl), at 0.01-0.7 M MgCl2 (optimum 0.1 M MgCl2) and at pH 6.0-9.0 (optimum pH
      7.5). The cells of both isolates were observed to lyse in distilled water. The
      minimum NaCl concentrations that prevented cell lysis were determined to be 8 %
      (w/v) for strain YC87(T) and 12 % (w/v) for strain YCA11. The major polar lipids
      of the two strains were identified as phosphatidylglycerol, phosphatidylglycerol
      phosphate methyl ester, phosphatidylglycerol sulfate and one major glycolipid
      chromatographically identical to sulfated mannosyl glucosyl diether; another
      major glycolipid and trace amounts of several unidentified lipids were also
      detected. The 16S rRNA gene sequences of the two strains were 99.8 % identical,
      showing 93.2-98.2 % similarity to members of the genus Halorubrum of the family
      Halobacteriaceae. The rpoB' gene similarity between strains YC87(T) and YCA11 was
      99.3 % and showed 87.5-95.2 % similarity to the closest relative members of the
      genus Halorubrum. The DNA G+C content of strains YC87(T) and YCA11 were
      determined to be 64.9 and 64.5 mol%, respectively. The DNA-DNA hybridization
      value between strain YC20(T) and strain YC77 was 87 % and the two strains showed
      low DNA-DNA relatedness with Halorubrum cibi JCM 15757(T) and Halorubrum
      aquaticum CGMCC 1.6377(T), the most related members of the genus Halorubrum. The
      phenotypic, chemotaxonomic and phylogenetic properties suggest that strains
      YC87(T) and YCA11 represent a novel species of the genus Halorubrum, for which
      the name Halorubrum rubrum sp. nov. is proposed. The type strain is YC87(T)
      (=CGMCC 1.12124(T) = JCM 18365(T)). 

PMID- 23949821
TI  - Mirabegron for overactive bladder syndrome.
AB  - Urinary incontinence, the involuntary leakage of urine, can result from
      abnormalities of the urinary tract or may be caused by other conditions and is
      sub-divided into a number of classifications including stress incontinence and
      urge urinary incontinence.(1) Urge urinary incontinence (UUI) is involuntary
      urine leakage accompanied by urgency of micturition.(2) Overactive bladder (OAB)
      syndrome is defined as urgency occurring with or without UUI and usually occurs
      with frequency and nocturia.(1) Wet OAB is associated with UUI, while dry OAB is
      not associated with incontinence. Current drug therapy for OAB involves the use
      of an antimuscarinic drug, of which there are a number available, such as
      oxybutynin, darifenacin, solifenacin and tolterodine.(1,3) ?Mirabegron is the
      first of a new class of drug, beta-3-adrenoreceptor agonists, licensed for
      symptomatic treatment of urgency, increased micturition frequency and/or urgency
      incontinence as may occur in adult patients with OAB syndrome.(4) Here we review
      the evidence for mirabegron. 

PMID- 23949822
TI  - Tadalafil for benign prostatic hyperplasia.
AB  - Tadalafil is a phosphodiesterase type-5 (PDE5) inhibitor licensed for the
      treatment of erectile dysfunction (ED) in adult males (Cialis-Lilly) and for the
      management of pulmonary arterial hypertension (Adcirca-Lilly).(1) The 5mg tablet
      was licensed in November 2012 for the treatment of the signs and symptoms of
      benign prostatic hyperplasia (BPH) in adult males (Cialis 5mg-Lilly).(2) In this
      article, we consider the evidence for tadalafil and how its use fits with current
      management strategies for BPH. 

PMID- 23949823
TI  - Editorial: Special issue on adult development and aging with IDD.

PMID- 23949824
TI  - People with intellectual disability: what do we know about adulthood and life
      expectancy?
AB  - Increases in the life expectancy of people with Intellectual Disability have
      followed similar trends to those found in the general population. With the
      exception of people with severe and multiple disabilities or Down syndrome, the
      life expectancy of this group now closely approximates with that of the general
      population. Middle and old age, which until 30 years ago were not recognized in
      this population, are now important parts of the life course of these individuals.
      Older adults with Intellectual Disabilities form a small, but significant and
      growing proportion of older people in the community. How these persons grow older
      and how symptoms and complications of the underlying cause of the Intellectual
      Disability will influence their life expectancy is of the utmost importance.

PMID- 23949825
TI  - Frailty and intellectual disability: a different operationalization?
AB  - Frailty is increasingly being recognized as a relevant health measure in older
      populations, associated with an increased risk of adverse health outcomes and
      care dependency. Because it is generally perceived that people with intellectual
      disabilities are "old" from age 50 onwards, frailty research in this group might
      lead to an understanding of factors, contributing to this perception. The
      development since the 1990s of conceptual and operational definitions of frailty
      has resulted in different approaches: biological (phenotype), multidimensional,
      and non-specific deficit accumulation. All approaches consider disability a
      consequence rather than a cause of frailty. This may be different for long
      disabled populations, which would have consequences for validity of frailty
      measures. First research shows that the different approaches are applicable to
      study populations with intellectual disabilities as well. Frailty as defined by
      both the phenotypic and deficit accumulation approach appears to develop
      considerably earlier and is more severe in people with intellectual disabilities
      than in the general older population, supporting the notion of early aging.
      Before any clinical implications can be outlined, health outcomes (validity),
      causes, and prevention of frailty should be investigated.

PMID- 23949826
TI  - Promoting healthy aging in adults with developmental disabilities.
AB  - This article reviews the research on health promotion for adults aging with
      developmental disabilities. First, it examines barriers to healthy aging,
      including health behaviors and access to health screenings and services. Second,
      it reviews the research on health promotion interventions, including physical
      activity interventions, health education interventions, and health care and
      screening preventive services. This review found evidence that the three types of
      health promotion interventions, physical activity and exercise, health education
      and mixed approaches, and health care and screening services can play a role in
      reducing health disparities for adults with developmental disabilities. Studies
      focusing primarily on physical activity and exercise tended to show improved
      fitness and some success in reducing obesity, reducing maladaptive behaviors, and
      improving alertness, though none of these studies showed longer term health
      benefits. The studies that took a more holistic approach by also including
      exercise and nutrition health education tended to show some evidence not only for
      changes in weight reduction but also for changes in health behavior attitudes
      (exercise self-efficacy, outcomes expectations, and barriers) and behaviors
      (e.g., dietary intake) and to a limited extent for improved life satisfaction.
      The literature on health screenings and services demonstrated the important role
      of health checks in identifying previously undetected conditions. These
      conditions include life threatening ones such as cancer and cardio-vascular
      disease, as well as less serious conditions that are often more common among
      adults with developmental disabilities and could be treated if caught early.

PMID- 23949827
TI  - Dementia and mild cognitive impairment in adults with intellectual disability:
      issues of diagnosis.
AB  - Individuals with intellectual disability (ID) are now living longer with the
      majority of individuals reaching middle and even "old age." As a consequence of
      this extended longevity they are vulnerable to the same age-associated health
      problems as elderly adults in the general population without ID. This includes
      dementia, a general term referring to a variety of diseases and conditions
      causing substantial loss of cognitive ability and functional declines; adults
      with Down syndrome are at especially high risk. A great deal of recent effort has
      focused on the very earliest detectable indicators of decline (and even prodromal
      stages of dementia-causing diseases). A condition called mild cognitive
      impairment (MCI) has been conceptually defined as a decline in functioning that
      is more severe than expected with typical brain aging but not severe enough to
      meet criteria for a diagnosis of dementia. Consensus criteria for both dementia
      and MCI have been developed for typically developing adults but are of limited
      applicability for adults with ID, given their pre-existing cognitive impairments.
      Early diagnosis will continue to be of growing importance, both to support
      symptomatic treatment and to prevent irreversible neuropathology when
      interventions are developed to slow or halt the progression of underlying
      disease. While the intellectual and developmental disabilities field has for some
      time recognized the need to develop best-practices for the diagnosis of MCI and
      dementia, there remains a pressing need for empirically based assessment methods
      and classification criteria.

PMID- 23949828
TI  - Aging and intellectual disability: insights from mouse models of Down syndrome.
AB  - Down syndrome (DS) is one of many causes of intellectual disability (ID), others
      including but not limited to, fetal alcohol syndrome, Fragile X syndrome, Rett
      syndrome, Williams syndrome, hypoxia, and infection. Down syndrome is
      characterized by a number of neurobiological problems resulting in learning and
      memory deficits and early onset Alzheimer's disease. The cognitive impairment in
      people with DS is virtually universal but varies considerably with respect to
      expressivity and severity. Significant advances in medical treatment and social
      inclusion have increased longevity in people with DS resulting in an increased
      aging population, thus highlighting the significance of early onset of dementia
      and the importance of identifying pharmacotherapies to treat DS-associated health
      complications in adults. Given its prevalence and established mouse models, this
      review will focus on ID in the DS population; specifically, the superimposed
      effect of aging on the complications already manifest in DS adults and the
      cognitive insights gained from studies on mouse models of DS.

PMID- 23949829
TI  - Atypical aging in Down syndrome.
AB  - At present, there may be over 210,000 people with Down syndrome (DS) over the age
      of 55 in the United States (US) who have significant needs for augmented services
      due to circumstances related to ordinary and/or pathological aging. From 1979
      through 2003, the birth prevalence of DS rose from 9.0 to 11.8 (31.1%) per 10,000
      live births in 10 representative US regions. This increase, largely due to women
      conceiving after age 35, portends an ever-growing population of people with DS
      who may be subject to pathogenic aging. Whereas Trisomy 21 is one of the most
      widespread genetic causes of intellectual disability (ID), it still is one of the
      least understood of all genetic ID syndromes. While longevity in people with DS
      has improved appreciably in as modest a period as 30 years, age-specific risk for
      mortality still is considerably increased compared both with other people with ID
      or with the typically developing population. The penetrance of the phenotype is
      widely distributed, even though a consistent genotype is assumed in 95% of the
      cases. Some, but not all body systems, exhibit signs of premature or accelerated
      aging. This may be due to both genetic and epigenetic inheritance. We now know
      that the long-term outcome for people with DS is not as ominous as once
      contemplated; a number of people with DS are living into their late 60s and 70s
      with few if any major signs of pathogenic aging. Alzheimer's disease (AD), a
      devastating disease that robs a person of their memory, abilities and
      personality, is particularly common in elder adults with DS, but is not a
      certainty as originally thought, some 20% to 30% of elder adults with DS might
      never show any, or at most mild signs of AD. DS has been called a mature well
      understood syndrome, not in need of further research or science funding. We are
      only beginning to understand how epigenetics affects the phenotype and it may be
      feasible in the future to alter the phenotype through epigenetic interventions.
      This chapter is divided into two sections. The first section will review typical
      and atypical aging patterns in somatic issues in elder adults with DS; the second
      section will review the multifaceted relationship between AD and DS.

PMID- 23949831
TI  - Aging in rare intellectual disability syndromes.
AB  - This review highlights several methodological challenges involved in research on
      aging, health, and mortality in adults with rare intellectual disability
      syndromes. Few studies have been performed in this area, with research obstacles
      that include: the ascertainment of older adults with genetic versus clinical
      diagnoses; likelihood that adults will not receive adequate health care and
      referrals to genetic specialists; cohort differences related to generational and
      treatment effects; and increased mortality and selective survival biases. Even
      so, aging in Prader-Willi and Williams syndromes are reviewed as they reveal new
      insights into the phenotypic expression and treatment options for older adults
      with these disorders. The review ends with recommendations for future research
      that takes better advantage of genetic advances, changes in adult phenotypes, and
      ties across syndrome-specific research silos. Although aging in rare
      neurodevelopmental disorders is barely on the research landscape, the field
      stands to learn much from these older adults.

PMID- 23949832
TI  - Health, functioning, and participation of adolescents and adults with cerebral
      palsy: a review of outcomes research.
AB  - With medical advances, more individuals with cerebral palsy (CP) syndromes who
      reside in developed countries are surviving to adolescence and adulthood.
      However, there continues to be a paucity of research examining long-term health,
      functional activities, and participatory outcomes over their life-course. This
      article reviews the current literature assessing adult outcomes for individuals
      with CP within the framework of the International Classification of Functioning
      (ICF), Disability, and Health model of enablement. Preliminary data over the last
      decade indicate that among adults with cerebral palsy without intellectual
      disability, 60-80% completed high school, 14-25% completed college, up to 61%
      were living independently in the community, 25-55% were competitively employed,
      and 14-28% were involved in long term relationships with partners or had
      established families. These outcomes occurred with biomedical advances in the
      management of spasticity, deformity, and medical co-morbidities, as well as with
      concurrent policy initiatives to increase access to a continuum of habilitative
      and education services. Although we have incomplete population data to inform
      comprehensive life-course planning, there are opportunities to create clinical
      and translational community networks with improved measures of functioning and
      participation that can better inform us about the factors influencing lifespan
      development of people with CP.

PMID- 23949830
TI  - Fragile X syndrome: an aging perspective.
AB  - Cognitive and behavioral correlates of molecular variations related to the FMR1
      gene have been studied rather extensively, but research about the long-term
      outcome in individuals with fragile X spectrum disorders remains sparse. In this
      review, we present an overview of aging research and recent findings in regard to
      cellular and clinical manifestations of aging in fragile X syndrome, and the FMR1
      premutation.

PMID- 23949833
TI  - Gestational weight gain in insulin-resistant pregnancies.
AB  - OBJECTIVE: To examine the Institute of Medicine (IOM) guidelines for gestational
      weight gain (GWG) in insulin-resistant pregnancy. STUDY DESIGN: Secondary
      analysis of a prospective cohort of 435 women with type 2 or gestational diabetes
      from 2006 to 2010. The exposure was categorized as GWG less than, within or
      greater than the IOM recommendations for body mass index. The maternal outcome
      was a composite of preeclampsia, eclampsia, third- to fourth-degree laceration,
      readmission or wound infection. The neonatal outcome was a composite of preterm
      delivery, level 3 nursery admission, oxygen requirement >6 h, shoulder dystocia,
      5-min Apgar?3, umbilical cord arterial pH<7.1 or base excess <-12. Secondary
      outcomes were cesarean delivery (CD), macrosomia and small for gestational age
      (SGA). RESULT: Incidence of the maternal outcome did not differ with GWG
      (P=0.15). Women gaining more than recommended had an increased risk of CD
      (relative risk (RR) 1.31, 95% confidence interval (CI) 1.01 to 1.69) and the
      neonatal outcome (RR 1.40, 95% CI 1.01 to 1.95) compared with women gaining
      within the IOM recommendations. Women gaining less than recommended had an
      increased risk of SGA (RR 3.29, 95% CI 1.09 to 9.91) without a decrease in the
      risk of the maternal outcome (RR 0.93, 95% CI 0.49 to 1.78) or CD (RR 0.74, 95%
      CI 0.40 to 1.37) compared with women gaining within the IOM recommendations.
      CONCLUSION: Women with insulin resistance should be advised to gain within the
      current IOM guidelines.

PMID- 23949834
TI  - Efficacy of clonidine versus phenobarbital in reducing neonatal morphine sulfate
      therapy days for neonatal abstinence syndrome. A prospective randomized clinical
      trial.
AB  - OBJECTIVE: To compare the efficacy of clonidine versus phenobarbital in reducing
      morphine sulfate treatment days for neonatal abstinence syndrome (NAS). STUDY
      DESIGN: Prospective, non-blinded, block randomized trial at a single level III
      NICU (Neonatal Intensive Care Unit). Eligible infants were treated with a
      combination of medications as per protocol. Primary outcome was treatment days
      with morphine sulfate. Secondary outcomes were the mean total morphine sulfate
      dose, outpatient phenobarbital days, adverse events and treatment failures.
      RESULTS: A total of 82 infants were eligible, of which 68 were randomized with 34
      infants in each study group. Adjusting for covariates phenobarbital as compared
      with clonidine had shorter morphine sulfate treatment days (-4.6, 95% confidence
      interval (CI): -0.3, -8.9; P=0.037) with no difference in average morphine
      sulfate total dose (1.1 mg kg(-1), 95% CI: -0.1, 2.4; P=0.069). Post-discharge
      phenobarbital was continued for an average of 3.8 months (range 1 to 8 months).
      No other significant differences were noted. CONCLUSION: Phenobarbital as adjunct
      had clinically nonsignificant shorter inpatient but significant overall longer
      therapy time as compared with clonidine.

PMID- 23949835
TI  - Emotional distress in mothers of preterm hospitalized infants: a feasibility
      trial of nurse-delivered treatment.
AB  - OBJECTIVE: Mothers of preterm infants in a hospital neonatal intensive care unit
      (NICU) are at risk for clinically significant depression and anxiety, but for
      these women their own treatment is likely a secondary priority. This study
      evaluated the feasibility, acceptability and effectiveness of an evidence-based,
      nurse-delivered, on-site depression treatment: listening visits (LVs). STUDY
      DESIGN: Therapeutic LVs were delivered on site to 23 distressed mothers of NICU
      infants. The intervention was conducted by a neonatal nurse practitioner and the
      outcome was examined in an open-trial, pre-post evaluation. RESULT: A part-time
      nurse practitioner delivered six LVs to each participant within a 1-month time
      frame. LVs were associated with significantly improved mood and well-being in
      mothers. The majority of eligible women took advantage of LVs and felt satisfied
      with their care. CONCLUSION: This open trial provides 'proof-of-concept', with
      results that warrant further evaluation in a multisite randomized controlled
      trial.

PMID- 23949837
TI  - Preterm birth and neonatal mortality in a rural Bangladeshi cohort: implications
      for health programs.
AB  - OBJECTIVE: To estimate the burden of prematurity, determine gestational age (GA)
      specific neonatal mortality rates and provide recommendations for country
      programs. STUDY DESIGN: Prospective data on pregnancy, childbirth, GA and newborn
      mortality collected by trained community health workers from 10 585 mother
      newborn pairs in a community-based study. RESULT: A total of 19.4% of newborn
      infants were preterm; 13.5% were late preterm (born between 34 and 36 weeks of
      gestation), 3.3% were moderate preterm (born at 32 to 33 weeks) and 2.6% were
      extremely preterm (born at 28 to 31 weeks of gestation). Preterm babies
      experienced 46% of all neonatal deaths; 40% of preterm deaths were in late
      preterm, 20% in moderate preterm and 40% in very preterm infants. The population
      attributable fraction of neonatal mortality in premature babies was 0.16 for very
      preterm, 0.07 for moderately preterm and 0.10 for late preterm. CONCLUSION: In
      settings where the majority of births and newborn deaths occur at home and
      successful referral is a challenge, moderate and late preterm babies may be an
      important target group for home-based or first-level facility-based management.

PMID- 23949836
TI  - Accounting for variation in length of NICU stay for extremely low birth weight
      infants.
AB  - OBJECTIVE: To develop a length of stay (LOS) model for extremely low birth weight
      (ELBW) infants. STUDY DESIGN: We included infants from the California Perinatal
      Quality Care Collaborative with birth weight 401 to 1000 g who were discharged to
      home. Exclusion criteria were congenital anomalies, surgery and death. LOS was
      defined as days from admission to discharge. As patients who died or were
      transferred to lower level of care were excluded, we assessed correlation of
      hospital mortality rates and transfers to risk-adjusted LOS. RESULTS: There were
      2012 infants with median LOS 79 days (range 23 to 219). Lower birth weight, lack
      of antenatal steroids and lower Apgar score were associated with longer LOS.
      There was negligible correlation between risk-adjusted LOS and hospital mortality
      rates (r=0.0207) and transfer-out rates (r=0.121). CONCLUSION: Particularly
      because ELBW infants have extended hospital stays, identification of unbiased and
      informative risk-adjusted LOS for these infants is an important step in
      benchmarking best practice and improving efficiency in care.

PMID- 23949838
TI  - What do preservice teachers from the USA and the UK know about dyslexia?
AB  - The purpose of the study was to examine the knowledge base of preservice teachers
      from the USA and the UK of dyslexia as a language-based learning disability. A
      survey (both US and UK versions) was constructed using current research-based
      understandings of dyslexia as a language-based learning disability. One hundred
      and one preservice teachers from the USA and 70 preservice teachers from the UK
      were administered the survey. Results indicated that participants in the two
      groups demonstrated some similar accurate knowledge about dyslexia as well as
      displaying some common misunderstandings about dyslexia. Recommendations
      concerning preservice teacher preparation and professional development for in
      service teachers about dyslexia as well as future research directions are
      discussed.

PMID- 23949839
TI  - Impact of clinical pharmacist-based parenteral nutrition service for bone marrow
      transplantation patients: a randomized clinical trial.
AB  - PURPOSE: Parenteral nutrition (PN) is a well-documented supportive care which
      maintains the nutritional status of patients. Clinical pharmacists are often
      involved in providing PN services; however, few studies have investigated the
      effect of a clinical pharmacy-based PN service in resource-limited settings.
      METHODS: We designed a randomized clinical trial to compare the clinical
      pharmacist-based PN service (intervention group) with the conventional method
      (control group) for adult patients undergoing hematopoietic stem cell
      transplantation in Shariati Hospital, Tehran, Iran (2011-2012). In the
      intervention group, the clinical pharmacists implemented standard guidelines of
      nutrition support. The conventional method was a routine nutrition support
      protocol which was pursued for all patients in the bone marrow transplantation
      wards. Main study outcomes included nutritional status (weight, albumin, total
      protein, pre-albumin, and nitrogen balance), length of hospital stay, time to
      engraftment, rate of graft versus host disease, and mortality rate. Patients were
      followed for 3 months. RESULTS: Fifty-nine patients were randomly allocated to a
      study group. The overall intake (oral and parenteral) in the control group was
      significantly lower than standard daily needed calories (P < 0.01). Patients in
      the intervention group received fewer days of PN (10.7 +/- 4.2 vs. 18.4 +/- 5.5
      days, P < 0.01). All nutritional outcomes were either preserved or improved in
      the intervention group while the nutritional status in the control group was
      deteriorated (P values < 0.01). Length of hospital stay was significantly shorter
      in the intervention group (P < 0.01). Regarding PN complications, hyperglycemia
      was observed more frequently in the intervention group (34.5 %, P = 0.01). Two
      patients in the control group expired due to graft versus host disease at the 3
      month follow-up. CONCLUSION: A clinical pharmacist-based nutrition support
      service significantly improved nutritional status and clinical outcomes in
      comparison with the suboptimal conventional method. Future studies should assess
      the cost effectiveness of clinical pharmacists' PN services.

PMID- 23949840
TI  - Population-based comparison of two feeding tube approaches for head and neck
      cancer patients receiving concurrent systemic-radiation therapy: is a
      prophylactic feeding tube approach harmful or helpful?
AB  - PURPOSE: The purpose of this study is to compare patient outcomes between a
      therapeutic versus a prophylactic gastrostomy tube (GT) placement approach in
      patients treated with concurrent systemic and radiation (SRT) therapy for head
      and neck cancer (HNC). METHODS: Outcomes were compared between all HNC patients
      treated with concurrent SRT from January 2001 to June 2009 from a center that
      only places GTs therapeutically when clinically necessary (center A) versus a
      center that generally places them prophylactically (center B). RESULTS: A total
      of 445 patients with HNC were identified, with 63 % from center A. As
      anticipated, GTs were placed less commonly in center A compared to B (31 versus
      88 %; p < 0.001). Center B had a significantly higher number of GT complications
      (p < 0.001), including infection (16 versus 5 %), leakage (10 versus 2 %), and
      blockage (3 versus 1 %). Conversely, center A had a higher admission rate (27
      versus 13 %, p = 0.001), most prominent for GT-related issues (15 versus 6 %).
      Center B had higher GT dependence at 90 days post-radiation therapy (34 versus 12
      %; p < 0.001), but not at 1 year (11 versus 10 %; p = 0.74). There was no
      significant difference in the proportion of head and neck patients who had a 10 %
      weight loss at 1 year (compared to baseline) between centers A and B (42 versus
      53 %, p = 0.07). There was no significant difference in the overall survival (A
      versus B, HR = 0.99; p = 0.96). CONCLUSION: A prophylactic GT approach results in
      exposing higher number of patients to GT complications. The higher rate of
      hospitalizations using a therapeutic approach suggests that patients are sicker
      when GTs are required. Given the similar weight loss and survival, a therapeutic
      approach at an earlier stage of need may be a preferable approach, when access to
      prompt GT placement is available.

PMID- 23949841
TI  - Adipose tissue-derived stem cells show considerable promise for regenerative
      medicine applications.
AB  - The stromal-vascular cell fraction (SVF) of adipose tissue can be an abundant
      source of both multipotent and pluripotent stem cells, known as adipose-derived
      stem cells or adipose tissue-derived stromal cells (ADSCs). The SVF also contains
      vascular cells, targeted progenitor cells, and preadipocytes. Stromal cells
      isolated from adipose tissue express common surface antigens, show the ability to
      adhere to plastic, and produce forms that resemble fibroblasts. They are
      characterized by a high proliferation potential and the ability to differentiate
      into cells of meso-, ecto- and endodermal origin. Although stem cells obtained
      from an adult organism have smaller capabilities for differentiation in
      comparison to embryonic and induced pluripotent stem cells (iPSs), the cost of
      obtaining them is significantly lower. The 40 years of research that mainly
      focused on the potential of bone marrow stem cells (BMSCs) revealed a number of
      negative factors: the painful sampling procedure, frequent complications, and
      small cell yield. The number of stem cells in adipose tissue is relatively large,
      and obtaining them is less invasive. Sampling through simple procedures such as
      liposuction performed under local anesthesia is less painful, ensuring patient
      comfort. The isolated cells are easily grown in culture, and they retain their
      properties over many passages. That is why adipose tissue has recently been
      treated as an attractive alternative source of stem cells. Essential aspects of
      ADSC biology and their use in regenerative medicine will be analyzed in this
      article. 

PMID- 23949842
TI  - Cisplatin versus carboplatin in combination with third-generation drugs for
      advanced non-small cell lung cancer.
AB  - BACKGROUND: An estimated 220,000 new cases of non-small cell lung cancer (NSCLC)
      and 160,000 deaths are expected to occur in the US in 2013, representing about
      28% of cancer-related mortality. Approximately 75% of these people will have
      locally advanced or metastatic disease and will be treated in a palliative
      setting. Platinum-based combination chemotherapy has benefits in terms of
      survival and symptom control when compared with best supportive care. OBJECTIVES:
      To assess the efficacy and safety of carboplatin-based chemotherapy when compared
      with cisplatin-based chemotherapy, both in combination with a third-generation
      drug, in people with advanced NSCLC. To compare quality of life in people with
      advanced NSCLC receiving chemotherapy with cisplatin and carboplatin combined
      with a third-generation drug. SEARCH METHODS: We searched the following
      electronic databases: MEDLINE (via PubMed) (1966 to 6 March 2013), EMBASE (via
      Ovid) (1974 to 6 March 2013), Cochrane Central Register of Controlled Trials
      (CENTRAL; Issue 2, 2013), and LILACS (1982 to 6 March 2013). In addition, we
      handsearched the proceedings of the American Society of Clinical Oncology
      Meetings (January 1990 to March 2013), reference lists from relevant resources
      and the Clinical Trial.gov database. SELECTION CRITERIA: Randomised clinical
      trials comparing regimens with carboplatin or cisplatin combined with a third
      generation drug in people with locally advanced or metastatic NSCLC. We accepted
      any regimen and number of cycles that included these drugs, since there is no
      widely accepted standard regimen. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed search results and a third review author resolved
      any disagreements. We analysed the following endpoints: overall survival, one
      year survival, quality of life, toxicity and response rate. MAIN RESULTS: We
      included 10 trials with 5017 people, 3973 of whom were available for meta
      analysis. There was no difference between carboplatin-based and cisplatin-based
      chemotherapy in overall survival (hazard ratio (HR) 1.00; 95% confidence interval
      (CI) 0.51 to 1.97, I(2) = 0%) and one-year survival rate (risk ratio (RR) 0.98;
      95% CI 0.88 to 1.09, I(2) = 24%). Cisplatin had higher response rates when we
      performed an overall analysis (RR 0.88; 95% CI 0.79 to 0.99, I(2) = 3%), but
      trials using paclitaxel or gemcitabine plus a platin in both arms had equivalent
      response rates (paclitaxel: RR 0.89; 95% CI 0.74 to 1.07, I(2) = 0%; gemcitabine:
      RR 0.92; 95% CI 0.73 to 1.16, I(2) = 34%). Cisplatin caused more nausea or
      vomiting, or both (RR 0.46; 95% CI 0.32 to 0.67, I(2) = 53%) and carboplatin
      caused more thrombocytopenia (RR 2.00; 95% CI 1.37 to 2.91, I(2) = 21%) and
      neurotoxicity (RR 1.55; 95% CI 1.06 to 2.27, I(2) = 0%). There was no difference
      in the incidence of grade III/IV anaemia (RR 1.06; 95% CI 0.79 to 1.43, I(2) =
      20%), neutropenia (RR 0.96; 95% CI 0.85 to 1.08, I(2) = 49%), alopecia (RR 1.11;
      95% CI 0.73 to 1.68, I(2) = 0%) or renal toxicity (RR 0.52; 95% CI 0.19 to 1.45,
      I(2) = 3%). Two trials performed a quality of life analysis; however, they used
      different methods of measurement so we could not perform a meta-analysis.
      AUTHORS' CONCLUSIONS: The initial treatment of people with advanced NSCLC is
      palliative, and carboplatin can be a treatment option. It has a similar effect on
      survival but a different toxicity profile when compared with cisplatin.
      Therefore, the choice of the platin compound should take into account the
      expected toxicity profile and the person's comorbidities. In addition, when used
      with either paclitaxel or gemcitabine, the drugs had an equivalent response rate.

PMID- 23949843
TI  - Survey of inappropriate use of magnetic resonance imaging.
AB  - OBJECTIVE: There are concerns that not all costly advanced imaging is
      appropriate. However, studies about the appropriateness of magnetic resonance
      imaging (MRI) are sparse. The aim of this study was to review various MRI
      examinations done at a university hospital to determine whether there is
      inappropriate use. METHODS: Altogether 150 common MRIs (upper abdomen or liver,
      lumbar spine, knee, head and head of children performed under anaesthesia, 30
      each) were reviewed consecutively. The referrals and corresponding patient files
      were analysed by senior radiologists and the indications of the examinations were
      compared to the referral criteria. RESULTS: Seven per cent of the examinations
      were deemed inappropriate. All the MRIs of the head done on children were
      indicated. One to three examinations in all other subgroups were not indicated.
      The most common appropriate indications were ambiguous hepatic, pancreatic or
      adrenal lesions, prolonged lower back pain, suspicion of meniscus rupture, brain
      malignancy and developmental disorder of a child, respectively. CONCLUSIONS:
      Although the proportion of inappropriate examinations was not high; financial
      issues and the growing number of patients referred for MRI are of concern.
      Education and regular use of up-to-date referral guidelines could help to further
      improve appropriateness. MAIN MESSAGES: *Seven per cent of the MRI examinations
      analysed were inappropriate at a university hospital. *Everyday practices of a
      hospital may contribute to the level of appropriateness. *A survey of indications
      for previous MRI examinations might be helpful in various institutions.

PMID- 23949844
TI  - [Abstracts of the 111th Congress of the German Society of Ophthalmology.
      September 19-22, 2013. Berlin, Germany].

PMID- 23949845
TI  - Two RFID standard-based security protocols for healthcare environments.
AB  - Radio Frequency Identification (RFID) systems are widely used in access control,
      transportation, real-time inventory and asset management, automated payment
      systems, etc. Nevertheless, the use of this technology is almost unexplored in
      healthcare environments, where potential applications include patient monitoring,
      asset traceability and drug administration systems, to mention just a few. RFID
      technology can offer more intelligent systems and applications, but privacy and
      security issues have to be addressed before its adoption. This is even more
      dramatical in healthcare applications where very sensitive information is at
      stake and patient safety is paramount. In Wu et al. (J. Med. Syst. 37:19, 43)
      recently proposed a new RFID authentication protocol for healthcare environments.
      In this paper we show that this protocol puts location privacy of tag holders at
      risk, which is a matter of gravest concern and ruins the security of this
      proposal. To facilitate the implementation of secure RFID-based solutions in the
      medical sector, we suggest two new applications (authentication and secure
      messaging) and propose solutions that, in contrast to previous proposals in this
      field, are fully based on ISO Standards and NIST Security Recommendations.

PMID- 23949846
TI  - A biometric authentication scheme for telecare medicine information systems with
      nonce.
AB  - In recent years, the increased availability of lower-cost telecommunications
      systems and customized patients monitoring devices made it possible to bring the
      advantages of telemedicine directly into the patient's home. These telecare
      medicine information systems enable health-care delivery services. These systems
      are moving towards an environment where automated patient medical records and
      electronically interconnected telecare facilities are prevalent. Authentication,
      security, patient's privacy protection and data confidentiality are important for
      patient or doctor accessing to Electronic Medical Records (EMR). A secure
      authentication scheme will be required to achieve these goals. Many schemes based
      on cryptography have been proposed to achieve the goals. However, many schemes
      are vulnerable to various attacks, and are neither efficient, nor user friendly.
      Specially, in terms of efficiency, some schemes are resulting in high time cost.
      In this paper we propose a new authentication scheme that is using the
      precomputing to avoid the time-consuming exponential computations. Finally, it is
      shown to be more secure and practical for telecare medicine environments. 

PMID- 23949847
TI  - Potential role of Hedgehog signaling and microRNA-29 in liver fibrosis of IKKbeta
      deficient mouse.
AB  - Recent studies have reported that NF-kappaB mediated down-regulation of miRNA-29
      and lower expression of miRNA-29 promoted the deposition of collagens in fibrotic
      liver. Our previous research demonstrated that the increased Hedgehog (Hh)
      signaling, a key regulator for hepatic fibrogenesis, induced the severe hepatic
      fibrosis in the livers with impaired NF-kappaB signaling. These findings led us
      to investigate the effect of Hh and miRNA-29 on the hepatic fibrosis under
      dysregulated NF-kappaB signaling. In this study, we used IKKbeta(F/F) and IKKbeta
      deficient IKKbeta(DeltaHEP) mouse model with a defective NF-kappaB signaling
      pathway, and assessed the expression of the miRNA-29 family (miRNA-29a, miRNA
      29b, and miRNA-29c), Hh, and proliferation of MF-HSCs in liver from IKKbeta(F/F)
      mice and IKKbeta(DeltaHEP) mice both before and after MCDE treatment. The
      activation of NF-kappaB was significantly increased in MCDE diet-fed IKKbeta(F/F)
      mice compared to IKKbeta(DeltaHEP) mice. Expression of miRNA-29 family was
      greater in MCDE diet-fed IKKbeta(DeltaHEP) mice than IKKbeta(F/F) mice,
      demonstrating that the impaired NF-kappaB pathway was unable to suppress the
      expression of miRNA-29s after injury. However, expression of the Hh signaling
      pathway was greatly enhanced, and activation of Hh promoted the accumulation of
      MF-HSCs with impaired NF-kappaB, eventually increasing fibrogenesis in the
      damaged liver of IKKbeta(DeltaHEP) mice. Therefore, these results demonstrated
      that Hh signaling regulates the proliferation of MF-HSCs irrespective of the
      action of miRNA-29, eventually contributing hepatic fibrosis, when the NF-kappaB
      pathway is disrupted. 

PMID- 23949848
TI  - Effect of 3G cell phone exposure with computer controlled 2-D stepper motor on
      non-thermal activation of the hsp27/p38MAPK stress pathway in rat brain.
AB  - Cell phone radiation exposure and its biological interaction is the present
      concern of debate. Present study aimed to investigate the effect of 3G cell phone
      exposure with computer controlled 2-D stepper motor on 45-day-old male Wistar rat
      brain. Animals were exposed for 2 h a day for 60 days by using mobile phone with
      angular movement up to zero to 30 degrees . The variation of the motor is
      restricted to 90 degrees  with respect to the horizontal plane, moving at a pre
      determined rate of 2 degrees  per minute. Immediately after 60 days of exposure,
      animals were scarified and numbers of parameters (DNA double-strand break,
      micronuclei, caspase 3, apoptosis, DNA fragmentation, expression of stress
      responsive genes) were performed. Result shows that microwave radiation emitted
      from 3G mobile phone significantly induced DNA strand breaks in brain. Meanwhile
      a significant increase in micronuclei, caspase 3 and apoptosis were also observed
      in exposed group (P < 0.05). Western blotting result shows that 3G mobile phone
      exposure causes a transient increase in phosphorylation of hsp27, hsp70, and p38
      mitogen-activated protein kinase (p38MAPK), which leads to mitochondrial
      dysfunction-mediated cytochrome c release and subsequent activation of caspases,
      involved in the process of radiation-induced apoptotic cell death. Study shows
      that the oxidative stress is the main factor which activates a variety of
      cellular signal transduction pathways, among them the hsp27/p38MAPK is the
      pathway of principle stress response. Results conclude that 3G mobile phone
      radiations affect the brain function and cause several neurological disorders.

PMID- 23949849
TI  - Uterine artery suture: a preventive approach for pernicious placenta previa.
AB  - Pernicious placenta previa is an obstetric complication that results in a crisis
      situation for many patients. Most existing options deal with the problems after
      delivery leading to unfavorable outcomes. To circumvent this situation, a few
      preventive simple surgical options have been discussed in this paper. The
      highlight of the approach is the application of ascending uterine artery suture
      that drastically reduced the amount of bleeding as compared to that observed in
      regular surgeries. Combined with the placenta accrete location, wedge resection
      and 'patch' homeostasis of the serous membrane, the surgical modifications
      adopted effectively reduced the need for hysterectomy thus preserving the
      fertility of the patients for the future. Since fetuses were safely removed
      within 1-2 min, the Apgar scores of the neonates were also largely unaffected.

PMID- 23949850
TI  - Sema4D knockdown in oligodendrocytes promotes functional recovery after spinal
      cord injury.
AB  - Semaphorin4D (Sema4D) belongs to Semaphorins family and is secreted and membrane
      bound protein. Its function on angiogenesis and axon regeneration makes it an
      ideal therapeutic target for spinal cord injury (SCI). Here we examined Sema4D
      expression profile by real-time PCR and western blot and found Sema4D was
      upregulated after SCI. In vitro study showed Sema4D was not only expressed in
      oligodendrocytes but also in endothelial cells (ECs). Hypoxia can mimic Sema4D
      upregulation in both cell lines. Moreover, overexpression of Sema4D through
      lentivirus in ECs promoted tube formation. However, Sema4D overexpression in
      oligodendrocytes precursor cells (OPCs) inhibited neuron myelination in neuron
      oligodendrocyte co-culture system. Therefore, Sema4D knockdown in OPCs was
      applied in SCI rats. The results indicated that Sema4D knockdown significantly
      promoted functional recovery with blood-brain barrier score. Taken together, our
      data suggest that specific Sema4D knockdown in oligodendrocytes without
      disturbing its angiogenesis effect can be a beneficial strategy for SCI
      treatment. 

PMID- 23949851
TI  - Association between single-nucleotide polymorphism in CISH gene and
      susceptibility to tuberculosis in Chinese Han population.
AB  - The cytokine-inducible SRC homology 2 domain (CISH) gene is up-regulated by IL-2
      in response to infection, and inhibits microbial infection. The objective of the
      present study was to examine whether genetic variants of CISH (SNPs) are
      associated with increased susceptibility to tuberculosis (TB) in individuals of
      Chinese Han ethnicity. We sequenced five previously identified SNPs of CISH in
      patients with TB or healthy controls. Three of the SNPs, rs148685070 [position 
      639; C/C], rs414171 [position -292; A/T], and rs6768300 [position -163; C/G]) are
      located in the promoter region, while the fourth (rs2239751 [position +1320;
      A/C]) near the translation start site, and the fifth (rs622502 [position +3415;
      C/G]) in the third intron. The AA genotypes of the SNPs rs2239751 and rs414171
      were significantly associated with TB. Multivariate logistic regression analysis
      demonstrated that subjects with the rs414171 AA genotype were more likely to have
      TB than those with the AT genotype. By contrast, we did not observe genetic
      variants of the rs148685070 SNP. In conclusion, two genetic variants in CISH gene
      appear to increase susceptibility to TB in Chinese Han population. 

PMID- 23949853
TI  - Age structure and feeding of the neotropical grasshopper Cornops aquaticum
      (Bruner) (Orthoptera: Acrididae) on water hyacinth.
AB  - We aimed to evaluate the variation in the age structure of Cornops aquaticum
      (Bruner) population and its relation to the host plant biomass and the feeding of
      the different age classes of this grasshopper on the water hyacinth Eichhornia
      crassipes along 2 years, in a Parana River floodplain lake (Chaco, Argentina).
      Individuals of C. aquaticum were captured with a 70-cm diameter sweep and
      separated in nymphs A (instars I and II), nymphs B (instars III to VI), adult
      females, and adult males; host plant biomass was sampled using a ring with a 0.30
      m(2) diameter. Relative daily feeding of C. aquaticum population was calculated
      by multiplying the number of individuals captured per minute by the daily
      consumption by individual obtained in each age classes. We found that the age
      structure and the relative daily feeding of C. aquaticum varied between seasons
      and years. The highest values of grasshopper abundance, leaf biomass, and
      relative daily feeding of C. aquaticum population were observed in summer 2006.
      Plant biomass was directly correlated with nymph abundance and not correlated
      with adult abundance. Plant biomass available as refuge (leaves), food (laminas),
      and oviposition site (petioles) to C. aquaticum represented up to 62% of the
      total plant biomass. The results obtained in C. aquaticum show the importance of
      considering total plant biomass and plant biomass available for herbivores
      separately. Our study highlights the need to find an adequate method to estimate
      the density of C. aquaticum and other semiaquatic grasshoppers in the Parana
      River floodplain involving different seasons, years, and water phases (rising and
      falling).

PMID- 23949854
TI  - Mini-winkler extractor and pitfall trap as complementary methods to sample
      formicidae.
AB  - The aim of the present study was to evaluate the use of mini-Winkler extractor
      and pitfall traps as appropriate and complementary methods to sample ant
      communities in the phytophysiognomy mosaic in the Pocone Pantanal region, state
      of Mato Grosso, Brasil. Seven units were studied for landscape, located within a
      25 km(2) collection area, formed by thirty 250-m transects, at 1-km intervals in
      a 5 * 5 km area. Five collection points were marked in each transect at 50-m
      intervals, totaling 150 points. A collection was made at each sampling point with
      mini-Winkler extractor and pitfall traps. Using the mini-Winkler extractor, 1,088
      individuals were collected distributed in 20 genera and 55 species, with
      Solenopsis invicta Buren and Pheidole (gr. biconstricta) sp.1 as the most
      frequent ants. Using pitfall traps, 2,726 individuals distributed in 24 genera
      and 48 species were sampled and Dorymyrmex (gr. pyramicus) sp.1 and Pheidole (gr.
      biconstricta) sp.1 were the most frequent species. A significant difference
      between the methods was observed in measured species number. The Principal
      coordinates analysis discriminated two species groups exclusively sampled by the
      mini-Winkler extractor and another by the pitfall methods. Therefore, it was
      concluded that these methods were complementary for ant diversity inventories in
      the Pocone Pantanal region.

PMID- 23949852
TI  - Herbivore-induced plant volatiles to enhance biological control in agriculture.
AB  - Plants under herbivore attack synthetize defensive organic compounds that
      directly or indirectly affect herbivore performance and mediate other
      interactions with the community. The so-called herbivore-induced plant volatiles
      (HIPVs) consist of odors released by attacked plants that serve as important cues
      for parasitoids and predators to locate their host/prey. The understanding that
      has been gained on the ecological role and mechanisms of HIPV emission opens up
      paths for developing novel strategies integrated with biological control programs
      with the aim of enhancing the efficacy of natural enemies in suppressing pest
      populations in crops. Tactics using synthetic HIPVs or chemically/genetically
      manipulating plant defenses have been suggested in order to recruit natural
      enemies to plantations or help guiding them to their host more quickly, working
      as a "synergistic" agent of biological control. This review discusses strategies
      using HIPVs to enhance biological control that have been proposed in the
      literature and were categorized here as: (a) exogenous application of elicitors
      on plants, (b) use of plant varieties that emit attractive HIPVs to natural
      enemies, (c) release of synthetic HIPVs, and (d) genetic manipulation targeting
      genes that optimize HIPV emission. We discuss the feasibility, benefits, and
      downsides of each strategy by considering not only field studies but also
      comprehensive laboratory assays that present an applied approach for HIPVs or
      show the potential of employing them in the field. 

PMID- 23949855
TI  - Comparative biology of Euschistus heros (F.) (Hemiptera: Pentatomidae) feeding on
      cotton and soybean reproductive structures.
AB  - The neotropical brown stink bug, Euschistus heros (F.), is a phytophagous
      pentatomid that causes considerable economic losses in soybean crop, but it has
      been recently reported using cotton as a new host plant. Nymphs and adults of E.
      heros were raised on six different food sources composed of the reproductive
      structures of cotton and soybean plants: a standard diet (green-bean pods + raw
      peanuts + privet fruits), soybean seeds, soybean pods, cotton seeds, cotton
      bolls, and cotton floral buds. The following biological parameters were
      evaluated: nymph developmental time, instar duration, and survivorship; adult
      weight at emergence; male and female longevity; duration of pre-oviposition and
      oviposition periods; and female fecundity and fertility. Nymphal development time
      and survival, as well as the adult weight and fecundity of E. heros fed on cotton
      bolls and seeds were reduced if compared to those fed on soybean pods. The cotton
      floral buds did not support the immature development nor the reproduction of
      adults of E. heros. Most of the cotton plant structures fed to E. heros caused
      high nymph mortality and low adult fertility. Cotton, therefore, appeared to be
      an unsuitable host for the development and reproduction of E. heros. Therefore,
      our data may allow us to suggest that the occurrence of E. heros on cotton may be
      due to occasional dispersion in search for shelter. 

PMID- 23949856
TI  - Alkanes in flower surface waxes of Momordica cochinchinensis influence attraction
      to Aulacophora foveicollis Lucas (Coleoptera: Chrysomelidae).
AB  - Extraction, thin-layer chromatography, and gas chromatography-mass
      spectrophotometry analyses revealed 15 alkanes representing 97.14% of the total
      alkanes in the surface waxes of Momordica cochinchinensis Spreng flowers.
      Nonacosane was the prevailing alkane followed by hexatriacontane, nonadecane,
      heptacosane, and hentriacontane, accounting for 39.08%, 24.24%, 13.52%, 6.32%,
      and 5.12%, respectively. The alkanes from flower surface waxes followed by a
      synthetic mixture of alkanes mimicking alkanes of flower surface waxes elicited
      attraction of the female insect, Aulacophora foveicollis Lucas (Coleoptera:
      Chrysomelidae) between 2 and 10-MUg/mL concentrations in a Y-shaped glass tube
      olfactometer bioassay under laboratory conditions. Synthetic nonadecane from
      178.28-891.37 ng, heptacosane from 118.14-590.72 ng, and nonacosane at 784.73 ng
      showed attraction of the insect. A synthetic mixture of 534.82 ng nonadecane,
      354.43 ng heptacosane, and 2,354.18 ng nonacosane elicited highest attraction of
      A. foveicollis.

PMID- 23949857
TI  - Caribbean Sea Region Pyrrhocoroidea (Hemiptera: Pyrrhocoridae, Largidae).
AB  - A synopsis of the Pyrrhocoridae and Largidae (Pyrrhocoroidea) of the Caribbean
      Sea Region is given. Three new taxa are described: Dysdercus jamaicensis jindrai
      Stehlik n. subsp. (Dominican Republic); Largus fumosus fumosus Stehlik n. sp.
      (Panama-Barro Colorado Island); and Largus fumosus nigromembranaceus Stehlik n.
      subsp. (Panama). Largus pallidus Halstead is downgraded to a subspecies of Largus
      davisi Barber, i.e., L. davisi pallidus Halstead n. stat. The following new
      records are provided: Dysdercus (Dysdercus) andreae (Linnaeus) from Cayman
      Islands; Acinocoris elegans van Doesburg from Trinidad; Fibrenus pehlkei Schmidt
      and Largus maculatus Schmidt from Panama; and Largus obovatus (Barber) from
      Haiti. Altogether, we report 20 species and 3 subspecies of Pyrrhocoridae and 13
      species and 2 subspecies of Largidae from the Caribbean Sea Region. 

PMID- 23949858
TI  - Contrasting patterns of within-species morphological variation in two cactophilic
      Drosophila species (Diptera: Drosophilidae).
AB  - In this work, we investigated the morphological variation of the intromittent
      male copulatory organ (aedeagus) of specimens from natural populations of two
      cactophilic Drosophila species distributed in the southeast region of Brazil,
      Drosophila gouveai Tidon-Sklorz & Sene and Drosophila antonietae Tidon-Sklorz &
      Sene. It was explored how the within-species variability is arranged for both
      species, considering their historical and ecological features. Our results showed
      two distinct aedeagal morphologies for these species, and differences within
      species were observed only in D. gouveai as specimens could be distinguished by
      their population origin. In contrast, after size discrepancies correction, this
      feature was not detected in D. antonietae. The contrasting patterns of
      intraspecific variation, together with the other features exhibited by these two
      species, are most likely to be explained by differences in the historical host
      plant association and distribution and in demographic events, which determined
      the evolutionary history of these two South American cactophilic Drosophila
      species. 

PMID- 23949859
TI  - A review of the genus Alulatettix Liang (Orthoptera: Tetrigoidea: Tetrigidae).
AB  - The taxonomy of the tetrigid genus Alulatettix Liang is reviewed. A new species,
      Alulatettix orthomarginalis n. sp. is described. The annotated list and key to
      all known species of Alulatettix are given. 

PMID- 23949860
TI  - Telenomus remus Nixon egg parasitization of three species of Spodoptera under
      different temperatures.
AB  - Telenomus remus Nixon is a promising biocontrol agent as an egg parasitoid of
      Spodoptera spp., but the lack of information on the host-parasitoid interactions
      in this system precludes its applied use in agriculture. Therefore, we studied
      the parasitism capacity of T. remus on eggs of Spodoptera cosmioides (Walker),
      Spodoptera eridania (Cramer), and Spodoptera frugiperda (Smith) in a range of
      temperatures (19, 22, 25, 28, 31, and 34 +/- 1 degrees C) under controlled
      conditions (70 +/- 10% RH and 12 h photophase). Egg masses of Spodoptera spp.
      were offered to a single-mated T. remus female on a daily basis. More than 80%
      lifetime parasitism on eggs of S. cosmioides, S. frugiperda, and S. eridania was
      reached from 1 to 5, 1 to 7, and 1 to 9 days, respectively, at temperatures from
      19 to 34 degrees C. More than 80% parasitization was obtained at extreme
      temperatures for all hosts studied. Lifetime parasitization of S. frugiperda, S.
      cosmioides, and S. eridania was affected by temperature, with the lowest values
      for S. frugiperda (34 degrees C) and S. cosmioides (19 and 34 degrees C).
      Parasitization of S. eridania eggs was reduced around 18% at 28 and 31 degrees C,
      but dropped more severely at 34 degrees C. Parasitoid longevity was reduced as
      temperature increased. Thus, our data indicated that T. remus might be suitable
      as a biocontrol agent against S. eridania, S. cosmioides, and S. frugiperda in
      geographical areas that fit the temperature range studied here, even though T.
      remus parasitism was reduced at 34 degrees C. 

PMID- 23949861
TI  - Predation potential of Chilocorus cacti (Coleoptera: Coccinellidae) to the
      prickly pear cacti pest Dactylopius opuntiae (Hemiptera: Dactylopiidae).
AB  - Functional response of the predator Chilocorus cacti (Linnaeus) (Coleoptera:
      Coccinellidae) on five densities of Dactylopius opuntiae (Cockerell) (Hemiptera:
      Dactylopiidae) female adults was assessed under laboratory conditions. The
      searching efficiency of C. cacti significantly decreased as prey density
      increased. The logistic regression for the predator had a negative and
      significant linear parameter indicating a type II functional response. Non-linear
      regression for Holling predator equation estimated a handling time of 1.79 +/-
      0.129 h and attack rate coefficient of 0.1003 +/- 0.030. Most of this handling
      time was because the predator spent a lot of time removing the waxy coating that
      protects adult females of D. opuntiae. Chilocorus cacti consumes females of D.
      opuntiae in their reproductive stage; therefore, it could be an effective natural
      enemy to suppress or regulate low density populations of D. opuntiae, preventing
      them to reach high densities.

PMID- 23949862
TI  - Spatial distribution of Euschistus heros (F.) (Hemiptera: Pentatomidae) in
      soybean.
AB  - Soybean bugs are major crop pests that cause significant reduction in harvest
      yield and influence grain quality. The aim of this study was to verify the
      spatial distribution of Euschistus heros (F.) (Hemiptera: Pentatomidae) in
      conventional and transgenic soybean cultivars. The experiment was conducted
      during the 2010-2011 crop season in UNESP/FCAV, Jaboticabal, SP, Brazil, in two
      fields of 10,000-m(2) area that were subdivided into 100 plots (10 m * 10 m). The
      cultivars sown were M 7908 RR and its isoline M-SOY 8001. The number of the first
      to fifth instars and the number of adults were determined. To evaluate insect
      dispersion in the area, the following indices were used: variance/mean ratio,
      Morisita index, Green coefficient, and the k exponent of the negative binomial
      distribution. To study probabilistic models to describe the spatial distribution
      of the insects, the adjustments of the Poisson and negative binomial
      distributions were tested. The first to third instars showed aggregated spatial
      distribution, whereas the fourth and fifth instars, and adults, isolated or
      grouped, showed variation in the arrangement, ranging from moderately aggregated
      to randomly dispersed. During the adjustment of probability distributions, the
      negative binomial distribution model showed adjustment for the first to third
      instars, fourth and fifth instars, adults, and fourth and fifth instars plus
      adults.

PMID- 23949863
TI  - Species composition and abundance of Brevipalpus spp. on different citrus species
      in Mexican orchards.
AB  - We studied the abundance of Brevipalpus spp. in citrus orchards in the Mexican
      states of Yucatan, Quintana Roo and Campeche. Mites were collected from 100 trees
      containing a mixture of citrus species where sweet orange was always the main
      species. Eight collections were made at each location from February 2010 to
      February 2011. Mites from the genus Brevipalpus were separated from other mites
      surveyed and their abundance and relationships with the different citrus species
      were quantified throughout the collection period. A subsample of 25% of the total
      Brevipalpus mites collected were identified to species level and the interaction
      of mite species and citrus species were described. Brevipalpus spp. were present
      on all collection dates and their relative abundance was similar on all citrus
      species studies. The smallest number of mites collected was during the rainy
      season. Brevipalpus phoenicis (Geijskes) and Brevipalpus californicus (Banks)
      were the only two species present and they were found in all locations except
      Campeche, where only B. phoenicis was present. Yucatan and Campeche are at
      greater risk of leprosis virus transmission than Quintana Roo because the main
      vector, B. phoenicis, was more abundant than B. californicus. The implications of
      our results for the design of more accurate sampling and control methods for
      Brevipalpus spp. are discussed. 

PMID- 23949864
TI  - Development of Chrysomya albiceps (Wiedemann) (Diptera: Calliphoridae) in
      different pig tissues.
AB  - Chrysomya albiceps (Wiedemann) has been encountered breeding in animal carcasses
      and human bodies in many geographical regions. This species is considered an
      important postmortem indicator for Medical Legal Forensic Entomology. Studies
      have also demonstrated its capacity to develop in various natural and semi
      synthetic substrates. The present study was undertaken to examine the development
      of immature C. albiceps in four different pig tissues. Eggs of this fly were
      deposited in flasks containing liver, abdominal fat, meat, and brain tissues. The
      flasks were maintained in an incubator at 25 +/- 1 degrees C, 70 +/- 10%
      humidity, and 12-h/12-h photoperiod until emergence of the imagoes. Samples of
      the larvae were taken from different tissues/substrates to be weighed and
      measured. Their respective rates of development were accompanied. Comparisons
      among data from the different tissues indicated differences in the size and rate
      of development of larvae of the same age. Males emerged, on average, 1 day before
      females. Considerations as to the differences encountered for the estimate of
      postmortem interval were elaborated and consequences for the accuracy of the
      inferences discussed. The results indicate that such inferences should consider
      the disparities in the development of larvae presented by this species in
      different tissues.

PMID- 23949865
TI  - Assessment of the insecticidal potential of Eucalyptus urograndis essential oil
      against Rhodnius neglectus Lent (Hemiptera: Reduviidae).
AB  - The resistance of triatomines to pyrethroids has been reported in several Latin
      American countries, including Brazil, indicating the need for the development of
      new approaches for the control of vectors of the Chagas disease. In here, we
      evaluated the insecticidal potential of the essential oil of Eucalyptus
      urograndis (Myrtaceae) against unsexed third and fourth instars of Rhodnius
      neglectus Lent (Hemiptera: Reduviidae) in topical application, fumigation,
      surface contact, and repellency . The insecticidal activity of the essential oil
      tested was detected by topical application (LD50 = 0.1731 MUL/insect and LD99 =
      0.2948 MUL/insect for 24 h), fumigation (LC50 = 0.021 mL/mL air and LC99 = 0.1525
      mL/mL air for 24 h) and surface contact (LC50 = 0.7073 MUL/cm(2) and LC99 = 4.59
      MUL/cm(2) for 24 h). Mortality observed after 48-72-h exposure was very high and
      did not allow for any adjustment of the mortality curve. In the repellency assay,
      an effect was observed on 80% of tested nymphs. However, no repellency was
      observed after 24 h of exposure. Eucalyptus urograndis essential oil has a high
      insecticidal and repellent potential for R. neglectus nymphs, whether serving as
      a molecular model for new substances or as an alternative for the control of
      these insects.

PMID- 23949866
TI  - Genetic diversity and pathogenicity of Metarhizium spp. associated with the white
      grub Phyllophaga capillata (Blanchard) (Coleoptera: Melolonthidae) in a soybean
      field.
AB  - Phyllophaga capillata (Blanchard) was recently described as a soybean pest in
      Brazil. The occurrence of Metarhizium spp. associated with adults and their
      pathogenicity were investigated. Natural prevalence of Metarhizium anisopliae was
      0.51% in adults collected by light trap. Most Metarhizium isolates were
      identified as Metarhizium robertsii, although M. anisopliae sensu stricto and a
      few unidentified isolates were also found. Bioassays with representative isolates
      selected from different genetic groups resulted in <=5.6% confirmed mortality
      against larvae and adults, suggesting low potential of microbial control of this
      pest by use of indigenous Metarhizium isolates. 

PMID- 23949867
TI  - Maternal FMR1 premutation allele expansion and contraction in fraternal twins.
AB  - Fragile X syndrome results from an expansion of the CGG trinucleotide repeat in
      the 5' untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene.
      Expansion of a maternal premutation allele is the mechanism by which a full
      mutation allele arises; contraction of a maternal premutation allele is rare.
      Here we report on both an expansion and contraction of a maternal FMR1
      premutation allele in fraternal twins. The propositus was the product of a 29
      week gestation twin pregnancy and was referred for FMR1 testing due to
      developmental delay. A FMR1 full mutation with complete methylation was observed
      on Southern blot analysis. Evaluation of the maternal FMR1 gene by PCR revealed a
      normal and premutation allele with CGG repeat numbers of 30 and 93, respectively.
      Subsequent FMR1 testing on the twin sister of the propositus detected CGG repeat
      numbers of 30 and 54. The FMR1 CGG repeat number of the reproductive partner was
      30. The FMR1 CGG repeat 30 allele in the twin sister was determined to be of
      paternal origin and the FMR1 allele with a CGG repeat number of 54 was of
      maternal origin. This observation is particularly interesting not only because of
      the concomitant donation of a FMR1 expanded and contracted premutation allele in
      a twin pregnancy but also because of the significant degree of contraction (39
      repeats) of the maternal premutation allele.

PMID- 23949868
TI  - ARSH 10: Adolescent immunization revisited.
AB  - The emerging epidemiological shift in the incidence of vaccine preventable
      diseases like diphtheria, whooping cough and measles and the recent introduction
      of the attenuated combination vaccines (Tdap) and human papillomavirus (HPV)
      vaccine have necessitated the introduction of new vaccination schedules for the
      adolescents. On the back of this success in the west, it is timely to consider
      these schedules for the Indian scenario. The details of these vaccines as
      suggested by IAP COI and its programatic difficulties are discussed. The
      importance of providing evidence based, accurate information regarding adolescent
      immunization is emphasized. 

PMID- 23949869
TI  - Prediction model for low birth weight and its validation.
AB  - OBJECTIVE: To evaluate the factors associated with low birth weight (LBW) and to
      formulate a scale to predict the probability of having a LBW infant. METHODS:
      This hospital based case-control study was conducted in a tertiary care
      university hospital in North India. The study included 250 LBW neonates and 250
      neonates with birth weight >=2,500 g. Data were collected by interviewing mothers
      using pre-designed structured questionnaire and from hospital records. RESULTS:
      Factors significantly associated with LBW were inadequate weight gain by the
      mother during pregnancy (<8.9 kg), inadequate proteins in diet (<47 g/d),
      previous preterm baby, previous LBW baby, anemic mother and passive smoking. The
      prediction model made on these six variables has a sensitivity of 71.6 %,
      specificity 67.0 %, positive LR 2.17 and negative LR of 0.42 for a cut-off score
      of >=29.25. On validation, it has a sensitivity of 72 % and specificity of 64 %.
      CONCLUSIONS: It is possible to predict LBW using a prediction model based on
      significant risk factors associated with LBW.

PMID- 23949870
TI  - Tuberculin skin test, chest radiography and contact screening in children <5 Y:
      relevance in revised national tuberculosis control programme (RNTCP):
      correspondence.

PMID- 23949871
TI  - Tuberculin skin test, chest radiography and contact screening in children <5 Y:
      relevance in revised national tuberculosis control programme (RNTCP): author's
      reply.

PMID- 23949872
TI  - Vesiculopustular eruption in neonatal transient myeloproliferative disorder.
AB  - Transient myeloproliferative disorder (TMD) typically presents with pancytopenia,
      hepatosplenomegaly, and immature circulating white blood cells, and affects
      approximately 10 % of neonates with Down syndrome. The authors report a neonate
      with Down syndrome who developed acute widespread pustular eruptions as a sign of
      TMD. The white blood cell counts on the first day of life were markedly elevated,
      with blasts seen on examination of the peripheral blood smear. And the patient
      was noted to have a few erythematous papules and pustules especially on the face.
      On the following days pathergy positive crusted papules and pustules were
      increased and spread to trunk and extremities. Skin biopsy specimens showed
      pustular dermatitis, with subcorneal vesiculopustules and perivascular
      inflammation in superficial dermis. These lesions improved parallel with the
      hematologic improvement within two weeks. The authors aim to alert clinicians
      about this uncommon cause of vesiculopustular eruption with the present
      illustrative case and review the literature.

PMID- 23949874
TI  - Relaxin for preventing preterm birth.
AB  - BACKGROUND: Preterm birth is a leading cause of perinatal morbidity and
      mortality. Early animal and clinical studies have provided some evidence to
      support an inhibitory effect of relaxin on preterm birth for women in preterm
      labour. OBJECTIVES: To assess the effects of relaxin for women in preterm labour
      on preterm birth and associated maternal and neonatal/infant health outcomes.
      SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (30 June 2013), and the reference lists of relevant papers. SELECTION
      CRITERIA: Randomised and quasi-randomised controlled trials assessing the effects
      of relaxin compared with no treatment, a placebo, or an alternative tocolytic,
      for preventing preterm birth for women in preterm labour. Primary review outcomes
      included birth within 28 hours of treatment, birth within seven days of
      treatment, perinatal mortality, and a serious neonatal adverse outcome composite.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study
      eligibility, extracted data and assessed the risk of bias of included studies.
      MAIN RESULTS: We included three quasi-randomised controlled trials, with a total
      of 149 women and their babies. All three trials were at a high risk of bias. When
      comparing women receiving relaxin with those who did not receive relaxin, there
      was a significant reduction in birth within seven days of treatment in one trial
      of 30 women (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.29 to 0.87),
      yet no significant difference was seen for perinatal mortality in this trial (RR
      0.83, 95% CI 0.32 to 2.15). The second and third included trials did not report
      on any of the primary outcomes pre-specified in the review, including birth
      within 48 hours of treatment, birth within seven days of treatment, perinatal
      mortality, and serious neonatal adverse outcomes.One trial found a significant
      increase in pregnancy prolongation for women receiving relaxin (RR 8.00, 95% CI
      1.14 to 56.33; 30 women). None of the three included trials found significant
      differences in the outcomes of fetal death, neonatal death, birthweight or
      preterm birth, and no trial reported on longer-term outcomes for the babies.
      AUTHORS' CONCLUSIONS: There is limited randomised controlled trial evidence
      available on the effect of relaxin during pregnancy for preventing preterm birth
      for women in preterm labour. Evidence from one quasi-randomised trial suggested a
      reduction in birth within seven days of treatment for women receiving relaxin,
      compared with women in a control group, however this trial was at a high risk of
      bias and included only 30 women. There is thus insufficient evidence to support
      or refute the use of relaxin in women in preterm labour for preventing preterm
      birth.

PMID- 23949875
TI  - Depression and exposure to suicide predict suicide attempt.
AB  - OBJECTIVE: To examine the role of depression and exposure to peer or family
      suicide and their interaction as risk factors for adolescent suicide attempts.
      METHODS: The study used the public-use data set of the National Longitudinal
      Study of Adolescent Health (Add Health), which is a nationally representative
      stratified sample of U.S. high school students. Sample size was 4,719. Analyses
      predicted suicide attempts from preexisting depression and exposure to suicide of
      a friend or family member, controlling for previous suicide attempts, exposure,
      and depression. RESULTS: The greatest risk for future suicide attempts (relative
      risk = 3.3), was attributable to an attempt in the preceding year, controlling
      for preexisting and current depression and exposure. There was a main effect of
      exposure with the next highest relative risk of 3.2. A similar risk ratio, 3.2,
      was found for the difference between no depression and current severe depression,
      controlling for past depression and attempts. There was no evidence of an
      interaction between exposure to a peer or family member suicide attempt and
      depression. Supplementary analyses found that exposure to a friend or family
      member suicide attempt or completed suicide each added significantly to risk for
      adolescents regardless of depression levels. CONCLUSION: Exposure to suicidal
      behavior in a friend or family member poses risk equivalent to the risk posed by
      becoming severely depressed. Attending to such risks could benefit clinical
      practice with adolescence and public health suicide prevention efforts.

PMID- 23949876
TI  - Sources of apical defects on a high-sensitivity cardiac camera: experiences from
      a practice performance assessment.
AB  - Apical perfusion artifacts seen on a high-sensitivity camera warranted a practice
      performance assessment to evaluate contributions from soft-tissue attenuation,
      patient positioning, and image processing techniques. METHODS: Cardiac perfusion
      studies (n = 534) spanning 5 mo were retrospectively reviewed. Images were
      acquired with the patient in the upright position, and attenuation correction was
      used. Regression analysis and contingency tables correlated clinical data to the
      presence of apical artifacts. RESULTS: There was a positive correlation of with
      female sex (chi(2) = 32, P < 0.001), degree of overlying soft tissues (chi(2) =
      20, P < 0.002), and breast cleavage (chi(2) = 7, P < 0.008) and a negative
      correlation with angiography-confirmed disease (chi(2) = 6, P < 0.02). There was
      moderate interobserver agreement between 2 observers in determining the presence
      of apical defects (kappa= 0.44, 95% confidence interval = 0.19-0.69), and there
      was a perceived improvement of apical defects using fewer iterative updates
      (chi(2) = 8, P < 0.003). CONCLUSION: An understanding of sources contributing to
      imaging artifacts is a crucial portion of quality assessment in radiology and
      nuclear medicine. A practice performance assessment study at our institution
      showed that apical artifacts on a new-generation cardiac camera can be partially
      attributed to overlying soft-tissue attenuation and ameliorated by altering the
      reconstruction.

PMID- 23949877
TI  - Chemotherapy-related cognitive dysfunction: current animal studies and future
      directions.
AB  - Cognitive impairment is a potential long-term side effect of adjuvant
      chemotherapy that can have a major impact on the quality of life of cancer
      survivors. There is a growing number of preclinical studies addressing this
      issue, thereby extending our knowledge of the mechanisms underlying chemotherapy
      induced neurotoxicity. In this review, we will summarize the recent advances and
      important findings presented in these studies. Emerging challenges, such as the
      development of neuroprotective strategies, and the role of the blood-brain
      barrier on cognitive impairment will be described and future directions in this
      field of investigation will be outlined. 

PMID- 23949878
TI  - Biomarkers for pancreatic cancer: promising new markers and options beyond CA 19
      9.
AB  - Pancreatic adenocarcinoma accounts for nearly 90-95% of exocrine malignant tumors
      of the pancreas. Traditionally, overexpressed proteins/epitopes such as CA 19-9,
      CA-50, CEA, and many others were being used as pancreatic cancer tumor markers.
      The main utility of these biomarkers was in the diagnosis of pancreatic cancer as
      well as to assess response to chemotherapy and to determine prognosis and to
      predict tumor recurrence. However, these markers had significant limitations such
      as lack of sensitivity, false-negative results in certain blood groups, as well
      as false-positive elevation in the presence of obstructive jaundice. To
      circumvent these limitations, an extraordinary amount of research is being
      performed to identify an accurate tumor marker or a panel of markers that could
      aid in the management of the pancreatic cancer. Although this research has
      identified a large number and different variety of biomarkers, few hold future
      promise as a preferred marker for pancreatic cancer. This review provides an
      insight into exciting new areas of pancreatic biomarker research such as
      salivary, pancreatic juice, and stool markers that can be used as a noninvasive
      test to identify pancreatic cancer. This manuscript also provides a discussion on
      newer biomarkers, the role of microRNAs, and pancreatic cancer proteomics, which
      have the potential to identify a preferred tumor marker for pancreatic
      adenocarcinoma. This review further elaborates on important genetic changes
      associated with the development and progression of pancreatic cancer that holds
      the key for the identification of a sensitive biomarker and which could also
      serve as a therapeutic target.

PMID- 23949879
TI  - Meta-analysis of the association between GSTT1 null genotype and risk of
      nasopharyngeal carcinoma in Chinese.
AB  - Glutathione S-transferase T1 (GSTT1) null genotype has been proven to be
      associated with risks of many cancers. There were also many studies assessing on
      the association between GSTT1 null genotype and nasopharyngeal carcinoma risk in
      Chinese, but the findings from those studies were inconsistent. We performed a
      meta-analysis to provide a more precise assessment on the effect of GSTT1 null
      genotype on nasopharyngeal carcinoma risk. The PubMed and Wanfang databases were
      searched to identify eligible case-control studies on the association between
      GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese. The pooled
      odds ratios (OR) with corresponding 95% confidence intervals (95% CI) were used
      to assess the association. Eight case-control studies with a total of 3,702
      individuals were finally included in the meta-analysis. Meta-analysis of a total
      of eight studies showed that GSTT1 null genotype was significantly associated
      with increased risk of nasopharyngeal carcinoma in Chinese (OR = 2.27; 95% CI
      1.41-3.67; P = 0.001). The finding from cumulative meta-analysis showed that
      there was a trend of more obvious association between GSTT1 null genotype and
      risk of nasopharyngeal carcinoma in Chinese as data accumulated by publication
      year. Therefore, the GSTT1 null genotype is significantly associated with
      increased risk of nasopharyngeal carcinoma in Chinese.

PMID- 23949880
TI  - Positive link between variant Toll-like receptor 4 (Asp299Gly and Thr399Ile) and
      colorectal cancer patients with advanced stage and lymph node metastasis.
AB  - Toll-like receptors (TLRs) are considered as major endotoxin-signaling receptor
      and as crucial sensors of innate immunity. TLRs recognize pathogen-associated
      molecular patterns; induce effectors genes involving inflammatory cytokines and
      therefore initiation of adaptative immune responses against pathogens. Recently,
      it has been shown that TLRs are involved in tumor progression. In fact, increased
      level of TLR4 is associated with progression of colon malignancies. Even, TLR4
      polymorphism has been shown associated with susceptibility to have colorectal
      cancer. Our study aimed to investigate an association between TLR4 Asp299Gly
      (D299G) and Thr399Ile (T399I) polymorphisms in Tunisian patients with colorectal
      cancer. Using a primer extension method (SNaPshot), we genotyped two variants of
      TLR4 D299G and T399I in 100 patients with colorectal cancer and 140 healthy
      controls in Tunisian population. Interesting, we noted a significant association
      between T399I polymorphism and tumor differentiation (p = 0.027) and tumor
      architecture (p = 0.02) in colorectal cancer (CRC) patients. We also showed a
      significant association of D299G with an increased risk of advanced stage (p =
      0.03). Finally, we observed a positive link between D299G and T399I polymorphisms
      and CRC patients with lymph node (p = 0.00024; p = 0.0005, respectively) and
      metastasis (p = 0.001; p = 0.002, respectively). However, we found no evidence to
      support a significant association between TLR4 D299G and T399I polymorphisms and
      colorectal cancer susceptibility. Our findings suggest that TLR4 D299G and T399I
      polymorphisms are significantly associated with clinical features variables. TLR4
      polymorphisms may serve as biomarker of disease progression. Therefore, our
      results need confirmation in even larger studies. 

PMID- 23949881
TI  - SMAD7 rs12953717 polymorphism contributes to increased risk of colorectal cancer.
AB  - Mothers against decapentaplegic homolog 7 (SMAD7) rs12953717 polymorphism has
      been implicated to alter the risk of colorectal cancer (CRC), but the results are
      controversial. The objective of this study was to quantitatively evaluate the
      association between SMAD7 rs12953717 polymorphism and CRC susceptibility. A
      comprehensive search was conducted to identify all eligible studies of SMAD7
      rs12953717 polymorphism and CRC risk. Pooled odds ratio and 95% confidence
      interval were calculated using a fixed or random effects model. Statistical
      analysis was performed with Review Manager 5.0 and Stata 11. A total of 11 case
      control studies, including 12,058 cases and 11,444 controls, were identified. The
      combined results based on all studies suggested that rs12953717 was associated
      with CRC risk under all genetic models. When stratifying for race, the data
      showed that the rs12953717 was associated with a significantly increased CRC risk
      under all genetic models in Caucasians. Statistically significant association was
      found in all genetic models except in recessive model comparison in the subgroup
      of Asians. After stratifying the studies by study design, there was a significant
      association between rs12953717 polymorphism and CRC risk under all genetic models
      in the subgroup of population-based studies. Our study suggests that rs12953717
      polymorphism is associated with an increased CRC risk.

PMID- 23949882
TI  - Somatic and psychological effects of low-dose aromatase inhibition in men with
      obesity-related hypogonadotropic hypotestosteronemia.
AB  - INTRODUCTION: Reduced testosterone levels are frequently observed in obese men.
      Increased aromatase activity may be an etiological factor. OBJECTIVE: In this
      study, we evaluate the clinical effects of aromatase inhibition in obesity
      related hypogonadotropic hypotestosteronemia (OrHH). METHODS: Double-blind,
      placebo-controlled, 6-month trial in 42 obese men with a BMI >35 kg/m(2), and a
      serum total testosterone <10 nmol/l. All patients started on one tablet of 2.5
      mg/week, with subsequent dose escalation every month until a serum total
      testosterone of 20 nmol/l was reached. ENDPOINTS: Psychological function, body
      composition, exercise capacity, and glucose, lipid, and bone metabolism. RESULTS:
      Thirty-nine patients completed the study according to protocol. Letrozole
      decreased serum estradiol from 119.1+/-10.1 to 59.2+/-6.1 pmol/l (P<0.001), and
      increased serum LH from 3.3+/-0.3 to 8.8+/-0.9 U/l (P<0.0001) and serum total
      testosterone from 8.6+/-0.7 to 21.5+/-1.3 nmol/l (P<0.0001). Significant effects
      on the predefined endpoints were not observed. CONCLUSION: Despite a marked rise
      in serum testosterone, low-dose aromatase inhibition had no somatic or
      psychological effects in men with OrHH.

PMID- 23949883
TI  - [Trabeculectomy in uveitis associated with juvenile idiopathic arthritis: long
      term results in pediatric secondary glaucoma].
AB  - BACKGROUND: Secondary uveitic glaucoma in children can only be controlled in many
      cases by surgery. The aim of this study was to evaluate the outcome of
      trabeculectomy (TE) with administration of mitomycin C in children with secondary
      uveitis associated with juvenile idiopathic arthritis (JIA). MATERIALS AND
      METHODS: This study was a retrospective chart review of 21 children with uveitic
      glaucoma who underwent TE with administration of mitomycin C including analysis
      of complications, further interventions, additional surgical procedures to
      control intraocular pressure (IOP) and of the success rates after a mean follow
      up of 5 years. RESULTS: Defining success as an IOP <= 15 mmHg, the surgical
      success rate after TE was 55 % after 1 year and 38 % after 5 years but 43 % of
      the children required further IOP controlling operations in the long-term follow
      up. An IOP <= 15 mmHg was observed in 70 % of the children after 1 year and in 62
      % after 5 years. In regard to the overall success (with topical antiglaucomatous
      medication) the success rate increased to 71.4 % after 5 years. CONCLUSIONS: The
      results show that TE is a suitable surgical procedure to control IOP in secondary
      uveitic glaucoma of JIA patients. In the long-term follow up additional
      postoperative adjustments are necessary to control the IOP.

PMID- 23949884
TI  - [Hughes' operation and combined procedures].
AB  - BACKGROUND: The Hughes procedure is a standard and widely used technique for
      lower eyelid reconstruction. This paper presents the results of 55 patients who
      underwent reconstruction of the anterior and posterior lamella with the Hughes
      procedure at the University eye clinic in Salzburg between 2002 and 2012.
      PATIENTS AND METHODS: This study included 55 patients who underwent lower eyelid
      reconstruction performed with the Hughes procedure including a full skin graft.
      In 95 % of patients (52/55) this method was performed after tumor resection. The
      defect size of the lower lid was at least 10 mm horizontally and ranged between
      10 and 15 mm. Of the patients three were treated with a combined Hughes and
      Tenzel procedure whereas in five cases the Hughes procedure was combined with an
      autologous tarsoconjunctival flap of the contralateral upper lid and a local full
      skin rotational flap. RESULTS: In 42 out of 55 patients both the eyelid function
      as well as the restoration of good cosmesis could be achieved. In 6 out of the
      remaining 13 patients suffering from minor complications, the function and
      cosmesis were restored after secondary minor surgery or additional conservative
      treatment. For six patients, further reconstructive surgery was necessary and one
      experienced a major complication in the form of a recurrence of basal cell
      carcinoma necessitating exenteration. CONCLUSIONS: The Hughes procedure is a well
      suited technique for eyelid reconstruction of shallow defects extending beyond 10
      mm horizontally and involving up to 100 % of the eyelid. The latter require a
      combined procedure such as the Hughes procedure and an autologous
      tarsoconjunctival flap and skin graft.

PMID- 23949885
TI  - [Bilateral limbus parallel slightly prominent opacities in the corneal
      periphery].

PMID- 23949887
TI  - Sepsis and multiorgan dysfunction. Abstracts of the 6th International Congress,
      Weimar Sepsis Update 2013-Consensus and Controversies. September 4-6, 2013.
      Weimer, Germany.

PMID- 23949888
TI  - Monitoring the endogenous steroid profile disruption in urine and blood upon
      nandrolone administration: An efficient and innovative strategy to screen for
      nandrolone abuse in entire male horses.
AB  - Nandrolone (17beta-hydroxy-4-estren-3-one) is amongst the most misused endogenous
      steroid hormones in entire male horses. The detection of such a substance is
      challenging with regard to its endogenous presence. The current international
      threshold level for nandrolone misuse is based on the urinary concentration ratio
      of 5alpha-estrane-3beta,17alpha-diol (EAD) to 5(10)-estrene-3beta,17alpha-diol
      (EED). This ratio, however, can be influenced by a number of factors due to
      existing intra- and inter-variability standing, respectively, for the variation
      occurring in endogenous steroids concentration levels in a single subject and the
      variation in those same concentration levels observed between different subjects.
      Targeting an efficient detection of nandrolone misuse in entire male horses, an
      analytical strategy was set up in order to profile a group of endogenous steroids
      in nandrolone-treated and non-treated equines. Experiment plasma and urine
      samples were steadily collected over more than three months from a stallion
      administered with nandrolone laurate (1 mg/kg). Control plasma and urine samples
      were collected monthly from seven non-treated stallions over a one-year period. A
      large panel of steroids of interest (n = 23) were extracted from equine urine and
      plasma samples using a C18 cartridge. Following a methanolysis step, liquid
      liquid and solid-phase extractions purifications were performed before
      derivatization and analysis on gas chromatography-tandem mass spectrometry (GC
      MS/MS) for quantification. Statistical processing of the collected data permitted
      to establish statistical models capable of discriminating control samples from
      those collected during the three months following administration. Furthermore,
      these statistical models succeeded in predicting the compliance status of
      additional samples collected from racing horses.

PMID- 23949889
TI  - Intellectual disability, unusual facial morphology and hand anomalies in sibs.
AB  - Here we report on a Portuguese family with three sisters who shared moderate
      intellectual disability, unusual facial morphology (short palpebral fissures;
      broad nasal tip; thin upper and lower vermillion; broad and pointed chin) and
      hand anomalies in two of them (short left third and fifth right metacarpals in
      one case; marked syndactyly between the third and fourth fingers in another). One
      of the sisters had microcephaly and short stature, and the other two were obese.
      Obesity and somewhat similar facial features were also present in the otherwise
      healthy mother. Despite the overlap with several known syndromes (Albright
      osteodystrophy; Filippi syndrome; Rubinstein-Taybi syndrome; microdeletion 2q37),
      we suggest this condition is previously unreported, and most likely displays an
      autosomal recessive pattern of inheritance. (c) 2013 Wiley Periodicals, Inc. 

PMID- 23949886
TI  - The potential of stem cells in the treatment of cardiovascular diseases.
AB  - Although the adult mammalian heart was once believed to be a post-mitotic organ
      without any capacity for regeneration, recent findings have challenged this
      dogma. A modified view assigns to the mammalian heart a measurable capacity for
      regeneration throughout life. The ultimate goals of the cardiac regeneration
      field have been pursued by multiple strategies, including understanding the
      developmental biology of cardiomyocytes and cardiac stem and progenitor cells,
      applying chemical genetics, and engineering biomaterials and delivery methods
      that facilitate cell transplantation. Successful stimulation of endogenous
      regenerative capacity in injured adult mammalian hearts can benefit from studies
      of natural cardiac regeneration. 

PMID- 23949890
TI  - Dilated intracranial translucency and Blake's pouch cyst: first-trimester
      ultrasound markers of occipital cephalocele diagnosed using novel three
      dimensional reslicing technique.
AB  - Abnormal intracranial translucency (IT) (fourth ventricle) and a Blake's pouch
      cyst with normal brain stem cavity may be valuable first-trimester call signs of
      defects in the skull base. Here, we report a case of presumptive two-dimensional
      sonographic diagnosis of occipital cephalocele that was posed at the time of 11
      13 weeks aneuploidy scan. The two-dimensional sonographic finding elicited a
      detailed fetal neuroscan that was performed using either multiplanar mode or a
      novel three-dimensional reslicing and lightening technique. The use of three
      dimensional sonographic software and offline "navigation" within the volume of
      interest enabled operators to capture a diagnostic snapshot of the condition,
      enhancing quality imaging and early detection of the encephalic lesion.

PMID- 23949891
TI  - Increased (18)F-fluoroestradiol uptake in radiation pneumonia.
AB  - A 54-year-old metastatic breast cancer patient who had undergone chemotherapy and
      radiotherapy was transferred to our hospital for further treatment. We utilized
      (18)F-fluoroestradiol (FES) to assess the estrogen receptor (ER) status of
      metastatic lesions. Interestingly, high accumulation of (18)F-FES in pneumonia
      caused by radiation was detected. Hence, this draws oncologists' attention to the
      possible false-positive result of (18)F-FES, which may lead to inappropriate
      endocrine therapy. 

PMID- 23949892
TI  - Surgical referral criteria for degenerative rotator cuff tears: a Delphi
      questionnaire study.
AB  - Selecting the most appropriate patients to refer for surgery is crucial for high
      quality and efficient clinical care. However, there are no specific referral
      criteria to guide the referral of appropriate patients for rotator cuff repair
      surgery. The aim of the present study was to design robust surgical referral
      criteria for patients with degenerative rotator cuff tears using consensus
      methodology. A two-round Delphi questionnaire was undertaken with a nationally
      representative sample of 41 specialist shoulder surgeons experienced in rotator
      cuff repair. Surgical referral criteria for degenerative rotator cuff tear were
      developed where consensus of at least 70% agreement was achieved. The initial
      questionnaire consisted of 24 items. Consensus was reached on 14 items,
      including: severity of pain, functional limitation, the identification of fat
      atrophy, agreement that a course of physiotherapy should be attempted before
      surgical referral, and exclusion for those with an active frozen shoulder.
      However, there was no consensus with regard to the dimensions of the tear. The
      surgical referral criteria developed were novel and promising for patients with
      degenerative rotator cuff tears, and further research is required to examine
      their efficacy.

PMID- 23949894
TI  - Climate change and water resources in arid mountains: an example from the
      Bolivian Andes.
AB  - Climate change is projected to have a strongly negative effect on water supplies
      in the arid mountains of South America, significantly impacting millions of
      people. As one of the poorest countries in the region, Bolivia is particularly
      vulnerable to such changes due to its limited capacity to adapt. Water security
      is threatened further by glacial recession with Bolivian glaciers losing nearly
      half their ice mass over the past 50 years raising serious water management
      concerns. This review examines current trends in water availability and glacier
      melt in the Bolivian Andes, assesses the driving factors of reduced water
      availability and identifies key gaps in our knowledge of the Andean cryosphere.
      The lack of research regarding permafrost water sources in the Bolivian Andes is
      addressed, with focus on the potential contribution to mountain water supplies
      provided by rock glaciers.

PMID- 23949893
TI  - Error processing in current and former cocaine users.
AB  - Deficits in response inhibition and error processing can result in maladaptive
      behavior, including failure to use past mistakes to inform present decisions. A
      specific deficit in inhibiting a prepotent response represents one aspect of
      impulsivity and is a prominent feature of addictive behaviors in general,
      including cocaine abuse/dependence. Brain regions implicated in cognitive control
      exhibit reduced activation in cocaine abusers. The purposes of the present
      investigation were (1) to identify neural differences associated with error
      processing in current and former cocaine-dependent individuals compared to
      healthy controls and (2) to determine whether former, long-term abstinent cocaine
      users showed similar differences compared with current users. The present study
      used an fMRI Go/No-Go task to investigate differences in BOLD response to correct
      rejections and false alarms between current cocaine users (n = 30), former
      cocaine users (n = 29), and healthy controls (n = 35). Impulsivity trait measures
      were also assessed and compared with BOLD activity. Nineteen regions of interest
      previously implicated in errors of disinhibition were queried. There were no
      group differences in the correct rejections condition, but both current and
      former users exhibited increased BOLD response relative to controls for false
      alarms. In current users, the pregenual cingulate gyrus and left
      angular/supramarginal gyri overactivated. In former users, the right middle
      frontal/precentral gyri, right inferior parietal lobule, and left
      angular/supramarginal gyri overactivated. Overall, our results support a
      hypothesis that neural activity in former users differs more from healthy
      controls than that of current users due to cognitive compensation that
      facilitates abstinence. 

PMID- 23949895
TI  - Coupling socioeconomic and lake systems for sustainability: a conceptual analysis
      using Lake St. Clair region as a case study.
AB  - Applying sustainability at an operational level requires understanding the
      linkages between socioeconomic and natural systems. We identified linkages in a
      case study of the Lake St. Clair (LSC) region, part of the Laurentian Great Lakes
      system. Our research phases included: (1) investigating and revising existing
      coupled human and natural systems frameworks to develop a framework for this case
      study; (2) testing and refining the framework by hosting a 1-day stakeholder
      workshop and (3) creating a causal loop diagram (CLD) to illustrate the
      relationships among the systems' key components. With stakeholder assistance, we
      identified four interrelated pathways that include water use and discharge, land
      use, tourism and shipping that impact the ecological condition of LSC. The
      interrelationships between the pathways of water use and tourism are further
      illustrated by a CLD with several feedback loops. We suggest that this holistic
      approach can be applied to other case studies and inspire the development of
      dynamic models capable of informing decision making for sustainability. 

PMID- 23949897
TI  - Occult pyogenic liver abscess in an adolescent with type 2 diabetes.
AB  - Pyogenic liver abscess is a rare complication of diabetes, usually seen in adults
      greater than 50 years of age who have had diabetes for many years. We describe an
      18-year-old male with type 2 diabetes found to have a pyogenic liver abscess
      caused by Klebsiella pneumoniae, and show accompanying images from his evaluation
      for fever of unknown origin (FUO). We conclude that in a child or adolescent with
      FUO and diabetes, occult pyogenic liver abscess must be considered. 

PMID- 23949896
TI  - Novel truncating thyroglobulin gene mutations associated with congenital
      hypothyroidism.
AB  - Mutations in the thyroglobulin (TG) gene have been reported to cause congenital
      hypothyroidism (CH) and we have been investigating the genetic architecture of CH
      in a large cohort of consanguineous/multi-case families. Our aim in this study
      was to determine the genetic basis of CH in four affected individuals coming from
      two separate consanguineous families. Since CH is usually inherited in autosomal
      recessive manner in consanguineous/multi-case families, we adopted a two-stage
      strategy of genetic linkage studies and targeted sequencing of the TG gene. First
      we investigated the potential genetic linkage of families to any known CH locus
      using microsatellite markers and then determined the pathogenic mutations in
      linked-genes by Sanger sequencing. Both families showed potential linkage to TG
      locus and we detected two previously unreported nonsense TG mutations (p.Q630X
      and p.W637X) that segregated with the disease status in both families. This study
      highlights the importance of molecular genetic studies in the definitive
      diagnosis and classification of CH, and also adds up to the limited number of
      nonsense TG mutations in the literature. It also suggests a new clinical testing
      strategy using next-generation sequencing in all primary CH cases. 

PMID- 23949898
TI  - Saxagliptin add-on therapy to insulin with or without metformin for type 2
      diabetes mellitus: 52-week safety and efficacy.
AB  - BACKGROUND: Achievement of glycemic control is an important objective in the
      management of type 2 diabetes mellitus (T2DM). OBJECTIVE: The objective of this
      study was to evaluate the safety and efficacy of the dipeptidyl peptidase-4
      inhibitor saxagliptin versus placebo as add-on therapy in patients with T2DM
      inadequately controlled with insulin alone or insulin plus metformin. METHODS:
      This was a long-term (28-week) extension of a short-term (24-week), randomized,
      double-blind, parallel-group trial of saxagliptin 5 mg once daily versus placebo
      as add-on therapy to open-label insulin or insulin plus metformin therapy
      totaling 52 weeks of treatment. In contrast with the goal of maintaining a stable
      insulin dosage during the short-term phase, during the extension phase the
      insulin dosage was flexible and adjusted as deemed appropriate by the
      investigator. The study was conducted in a clinical practice setting, including
      family practice and hospital sites. Patients with T2DM aged 18-78 years with
      glycated hemoglobin (HbA1c) 7.5-11 % on a stable insulin regimen (30-150 U/day
      with or without metformin) for >=8 weeks at screening were included in the study.
      Patients were stratified by metformin use and randomly assigned 2:1 to oral
      saxagliptin 5 mg (n = 304) or placebo (n = 151) once daily. All patients who
      completed the initial 24 weeks of treatment were eligible to participate in the
      28-week extension, regardless of whether they had required rescue treatment. The
      main outcome measure was change in HbA1c from baseline to week 52. RESULTS: In
      general, the outcomes achieved at week 24 were sustained to week 52. Adjusted
      mean change from baseline HbA1c at week 52 was greater with saxagliptin (-0.75 %)
      versus placebo (-0.38 %); the adjusted between-group difference was -0.37 % (95 %
      CI -0.55 to -0.19); between-group differences were similar in patients treated
      with metformin (-0.37 % [95 % CI -0.59 to -0.15]) and without metformin (-0.37 %
      [95 % CI -0.69 to -0.04]). At week 52, a greater proportion of patients receiving
      saxagliptin achieved HbA1c <7 % than those receiving placebo (21.3 vs. 8.7 %;
      between-group difference 12.6 % [95 % CI 6.1-19.1]). The increase from baseline
      in mean total daily insulin dose at week 52 was numerically smaller with
      saxagliptin (5.67 vs 6.67 U with placebo; difference, -1.01 U [95 % CI -3.24 to
      1.22]). During the 52-week study period, the proportion of patients reporting >=1
      adverse event (AE) was 66.4 % with saxagliptin and 71.5 % with placebo, the
      majority being mild or moderate in intensity. The most common AEs (>=5 % with
      saxagliptin or placebo) were urinary tract infection, nasopharyngitis, upper
      respiratory tract infection, headache, influenza, and pain in extremity; the
      incidence of each AE was similar between treatment groups. In the saxagliptin and
      placebo groups, the incidence of reported hypoglycemia was 22.7 and 26.5 %,
      respectively; the incidence of confirmed hypoglycemia (fingerstick glucose <=50
      mg/dL [<=2.77 mmol/L] with characteristic symptoms) was 7.6 and 6.6 %,
      respectively. Adjusted mean change from baseline body weight was +0.8 kg with
      saxagliptin and +0.5 kg with placebo. CONCLUSION: Saxagliptin 5 mg once daily as
      add-on to insulin, with or without concomitant metformin, produced a durable
      improvement in glycemic control and was well tolerated over 52 weeks of
      treatment.

PMID- 23949899
TI  - Efficacy and safety of mildronate for acute ischemic stroke: a randomized, double
      blind, active-controlled phase II multicenter trial.
AB  - BACKGROUND AND OBJECTIVE: Mildronate, an inhibitor of carnitine-dependent
      metabolism, is considered to be an anti-ischemic drug. This study is designed to
      evaluate the efficacy and safety of mildronate injection in treating acute
      ischemic stroke. METHODS: We performed a randomized, double-blind, multicenter
      clinical study of mildronate injection for treating acute cerebral infarction.
      113 patients in the experimental group received mildronate injection, and 114
      patients in the active-control group received cinepazide injection. In addition,
      both groups were given aspirin as a basic treatment. Modified Rankin Scale (mRS)
      score was performed at 2 weeks and 3 months after treatment. National Institutes
      of Health Stroke Scale (NIHSS) score and Barthel Index (BI) score were performed
      at 2 weeks after treatment, and then vital signs and adverse events were
      evaluated. RESULTS: A total of 227 patients were randomized to treatment (n =
      113, mildronate; n = 114, active-control). After 3 months, there was no
      significant difference for the primary endpoint between groups categorized in
      terms of mRS scores of 0-1 and 0-2 (p = 0.52 and p = 0.07, respectively). There
      were also no significant differences for the secondary endpoint between groups
      categorized in terms of NIHSS scores of >5 and >8 (p = 0.98 and p = 0.97,
      respectively) or BI scores of >75 and >95 (p = 0.49 and p = 0.47, respectively)
      at 15 days. The incidence of serious adverse events was similar between the two
      groups. CONCLUSION: Mildronate injection is as effective and safe as cinepazide
      injection in treating acute cerebral infarction.

PMID- 23949900
TI  - Mullerian cyst of the uterus misdiagnosed as ovarian cyst on pelvic sonography.
AB  - Mullerian cyst of the uterus, also known as endosalpingiosis, is rare and often
      can be misdiagnosed as adnexal cyst on pelvic sonography. A 47-year-old woman was
      referred for an incidental finding of a right adnexal mass on pelvic sonography,
      suspected to be an ovarian cyst. During laparoscopy, a pedunculated cystic mass
      arising from the right anterior uterine wall was seen. The mass was resected
      laparoscopically and histologic examination showed a benign Mullerian cyst of the
      uterus. Diagnosis of Mullerian cyst of the uterus can be challenging. However,
      with increased awareness, preoperative diagnosis of this condition should be
      possible sonographically.

PMID- 23949901
TI  - Exon skipping and severe childhood-onset obesity caused by a leptin receptor
      mutation.

PMID- 23949902
TI  - Syndesmosis injuries.
AB  - Traumatic injuries to the distal tibiofibular syndesmosis commonly result from
      high-energy ankle injuries. They can occur as isolated ligamentous injuries and
      can be associated with ankle fractures. Syndesmotic injuries can create a
      diagnostic and therapeutic challenge for musculoskeletal physicians. Recent
      literature has added considerably to the body of knowledge pertaining to injury
      mechanics and treatment outcomes, but there remain a number of controversies
      regarding diagnostic tests, implants, techniques, and postoperative protocols.
      Use of the novel suture button device has increased in recent years and shows
      some promise in clinical and cadaveric studies. This article contains a review of
      syndesmosis injuries, including anatomy and biomechanics, diagnosis,
      classification, and treatment options. 

PMID- 23949903
TI  - Drug laws and the 'derivative' problem.
AB  - The concept of a 'derivative' is used widely in chemistry, where its precise
      meaning depends on the circumstances. However, numerous examples of derivative
      also occur in domestic drugs legislation, some of which stem from the 1961 United
      Nations Single Convention on Narcotic Drugs. There is a commonly held view that
      only 'first-order' derivatives should be considered: substances that can be
      created from a parent structure in a single chemical reaction. In other words,
      'derivatives of derivatives' are excluded. However, some substances related to
      ecgonine (e.g. 2-carbomethoxytropinone) are clearly convertible to cocaine, even
      though this may require more than one reaction step. It follows that 2
      carbomethoxytropinone is a controlled drug, a situation that most chemists would
      regard as perverse. A more extreme example of the complexity of 'derivative' is
      shown by the conversion of thebaine to buprenorphine. Even though this requires
      six or more stages, the US Drug Enforcement Administration successfully argued in
      a 1986 case that for the purposes of the Controlled Substances Act, the number of
      steps required was irrelevant; buprenorphine was a derivative of thebaine.
      Because the term derivative is rarely defined in statutes, the legal status of
      some substances, such as 2-bromo-LSD, is uncertain. Although a number of
      definitions of derivative can be found in the chemical literature, no single
      definition is adequate to describe all situations where it occurs in legislation.
      Unless qualified, it is suggested that the term derivative should be avoided in
      any future legislation.

PMID- 23949904
TI  - Bufalin inhibits migration and invasion in human hepatocellular carcinoma SK-Hep1
      cells through the inhibitions of NF-kB and matrix metalloproteinase-2/-9
      signaling pathways.
AB  - Metastasis plays an important role in mortality of cancer patients. Migration and
      invasion are the major characteristics of tumor metastasis. The induction of
      matrix metalloproteinases (MMPs) such as MMP-2 and -9 are particularly important
      for the invasiveness of various cancer cells. Bufalin, a class of toxic steroids,
      was purified from the skin glands of Bufo gargarizans or Bufo melanostictus; it
      is known to inhibit proliferation of human cancer cells. In this study, we
      investigated the antiinvasive mechanisms of bufalin in the human hepatocellular
      cancer cell line SK-Hep1. Bufalin significantly reduced serum-induced cell
      invasion and migration. Furthermore, bufalin markedly inhibited MMP-2 and -9
      activity, mRNA expression and protein levels in SK-Hep1 cells. Bufalin attenuated
      phosphoinisitide-3-kinase (PI3K) and phosphorylation of AKT which was associated
      with reduced levels of nuclear factor kappa B (NF-kappaB). Bufalin also
      suppressed protein levels of FAK and Rho A, VEGF, MEKK3, MKK7, and uPA and it
      diminished NF-kappaB translocation. Based on these observations, we propose that
      bufalin is acts as an antiinvasive agent by inhibiting MMP-2 and -9 and involving
      PI3K/AKT and NF-kappaB pathways. Bufalin is a potential therapeutic agent that
      may have efficacy in preventing the invasion and metastasis of malignant liver
      tumors.

PMID- 23949906
TI  - Initial management of severe hyperglycemia in patients with type 2 diabetes: an
      observational study.
AB  - INTRODUCTION: Current guidelines recommend insulin for patients with type 2
      diabetes (T2D) and severe hyperglycemia, but this recommendation lacks sufficient
      evidence and poses practical challenges. It is unclear whether non-insulin
      treatments are effective in this setting. The objective of this study was to
      describe treatment strategies of T2D patients with severe hyperglycemia and
      identify which initial treatments, interventions, or patient characteristics
      correlated with successful glucose lowering. METHODS: This was a retrospective
      cohort study of 114 patients with T2D and a glycosylated hemoglobin (A1C) >=12%.
      Changes in A1C were compared between patients started on non-insulin medications
      versus insulin-based regimens. Regression analysis was performed to assess
      predictors of success in achieving A1C <=9% within 1 year. The main outcomes
      measures were change in A1C from baseline and predictors of success in achieving
      A1C <=9% within 1 year. RESULTS: At baseline, 43 patients (37.7%) started one or
      more non-insulin medications; 71 (62.3%) started insulin. Fifty-eight patients
      (50.8%) achieved an A1C <=9%. Predictors of success were newly diagnosed T2D,
      certified diabetes educator (CDE) visits, and less time to follow-up A1C; insulin
      therapy was not. Change in A1C was significantly better in the non-insulin cohort
      compared to the insulin cohort (-4.5% vs. -2.8%, p = 0.001). Newly diagnosed
      patients were less likely to start insulin therapy (20.8% vs. 73.3%, p < 0.001),
      less likely to use insulin at any point (29.2% vs 81.1%, p < 0.001), and more
      likely to achieve an A1C <=9% compared to patients with established T2D (87.5% vs
      41.1%, p < 0.001). CONCLUSION: Insulin therapy was used in roughly two-thirds of
      patients with severe hyperglycemia, but did not result in better glycemic control
      compared to non-insulin regimens. Rapid follow-up, more CDE visits, and a new
      diabetes diagnosis were predictors of successful glucose lowering. Patients with
      T2D and severe hyperglycemia, particularly those newly diagnosed, may be managed
      with non-insulin therapy.

PMID- 23949905
TI  - Six-month intragastric balloon treatment for obesity improves lung function, body
      composition, and metabolic syndrome.
AB  - BACKGROUND: The purpose of this study is to establish whether the use of an
      intragastric balloon (IGB) for 6 months improves lung function, metabolic
      parameters, and body fat distribution in patients with overweight/obesity and
      metabolic syndrome (MS). METHODS: This is a longitudinal and interventional study
      on 40 adults, whose anthropometric, laboratory, and lung function parameters were
      assessed and who underwent dual-energy X-ray absorptiometry (DXA) before
      implantation and after removal of IGB. RESULTS: The total lung capacity (TLC) (p
      = 0.0001), functional residual capacity (FRC) (p = 0.0001), residual volume (p =
      0.0005), and expiratory reserve volume (ERV) (p = 0.0001) were significantly
      reduced by IGB. The body mass index (BMI) significantly decreased from a median
      of 39.1 kg/m(2) at the beginning of the study to 34.5 kg/m(2) at the end of the 6
      month period (p = 0.0001). At the end of the study, 31 participants (77.5%) no
      longer met the diagnostic criteria of MS. The percentage of truncal, android,
      gynoid, and total fat investigated by DXA exhibited significant reductions (p =
      0.0001). Significant correlations were found between delta TLC and delta waist
      circumference (rho = -0.34; p = 0.03), delta FRC and delta IMC (rho = -0.39; p =
      0.01), delta ERV and delta BMI (rho = -0.44; p = 0.005), and delta ERV and delta
      high-density lipoprotein (HDL) (rho = -0.37; p = 0.02). Significant correlations
      were also found between delta ERV and delta truncal (rho = -0.51; p = 0.004),
      android (rho = -0.46; p = 0.01), gynoid (rho = -0.55; p = 0.001), and total fat
      (rho = -0.59; p = 0.0005). CONCLUSIONS: IGB efficiently induced weight loss and
      promoted the improvement of lung function parameters, with a reduction of the
      restrictive ventilatory defect. It also promoted improvements of MS and the
      pattern of body fat distribution.

PMID- 23949907
TI  - Ethanol ablation of benign thyroid cysts and predominantly cystic thyroid
      nodules: factors that predict outcome.
AB  - No study has so far investigated the relationship between aspirate color or
      degree of aspiration on the success of ethanol ablation (EA) of cystic thyroid
      nodules. We aimed to evaluate the efficacy of EA of benign cystic thyroid nodules
      and assess the relevant factors influencing the outcome. Over a 2-year period, 64
      benign cystic thyroid nodules in 62 patients were treated with EA. Several
      factors related to EA efficacy were evaluated, including the cystic component
      volume, volume and color of aspirates, degree of aspiration, and volume of
      injected ethanol. In all cases, we performed ultrasound follow-up for at least 12
      months after the last EA session to evaluate the collapsed cystic component. The
      64 treated nodules had aspirate colors that were red bloody (n = 3), dark bloody
      (n = 31), brownish (n = 15), greenish-yellow (n = 13), and colorless (n = 2). The
      degrees of aspiration were scant (n = 8), mild (n = 3), moderate (n = 8), and
      complete (n = 45). There was successful collapse of the cystic component after
      initial EA in 52 cases, but a repeat EA was employed in 12 failed cases.
      Statistical analysis showed that the degree of aspiration and color of aspirates
      correlated significantly with the success of EA. The results of this study
      suggest that complete aspiration of cystic contents was the most important factor
      in the efficacy of EA of benign cystic thyroid nodules, and greenish-yellow
      contents were closely related to scant or mild aspiration.

PMID- 23949908
TI  - Nalmefene: a review of its use in the treatment of alcohol dependence.
AB  - The opioid system modulator nalmefene (Selincro(r)) is approved in the EU for as
      needed use to reduce alcohol consumption in alcohol-dependent adults with a high
      drinking risk level. This article reviews the efficacy and tolerability of as
      needed oral nalmefene in the treatment of alcohol dependence, as well as
      summarizing its pharmacological properties. In two randomized, double-blind,
      multinational trials (ESENSE 1 and ESENSE 2), as-needed nalmefene significantly
      reduced the number of heavy drinking days (in both trials) and total alcohol
      consumption (in ESENSE 1) at month 6. In the randomized, double-blind,
      multinational SENSE trial, as-needed nalmefene significantly improved both of
      these endpoints at month 13, but not at month 6. As-needed nalmefene had a
      greater beneficial effect in the target population (i.e. alcohol-dependent
      patients with at least a high drinking risk level at screening and
      randomization), with post hoc analyses revealing significant reductions in both
      the number of heavy drinking days and total alcohol consumption at month 6 (in
      ESENSE 1 and ESENSE 2) and at month 13 (in SENSE). Oral nalmefene was generally
      well tolerated in patients with alcohol dependence, with the most commonly
      occurring adverse events including nausea, insomnia and dizziness. In conclusion,
      as-needed nalmefene provides an important new option for use in the treatment of
      alcohol dependence.

PMID- 23949909
TI  - Initial metabolic tumor volume measured by 18F-FDG PET/CT can predict the outcome
      of osteosarcoma of the extremities.
AB  - We evaluated the ability of metabolic and volumetric parameters measured by
      pretreatment (18)F-FDG PET/CT to predict the survival of patients with
      osteosarcoma of the extremities. METHODS: The records of 83 patients with
      American Joint Committee on Cancer stage II extremity osteosarcoma treated with
      surgery and chemotherapy were retrospectively reviewed. Imaging parameters
      (maximum standardized uptake value, metabolic tumor volume [MTV], total lesion
      glycolysis, and tumor volume based on MR images) were measured before treatment,
      and histologic responses to neoadjuvant chemotherapy were assessed by examination
      of postsurgical specimens. Receiver-operating-characteristic curve analyses and
      the Cox proportional hazards model were used to analyze whether imaging and
      clinicopathologic parameters could predict metastasis-free survival. RESULTS: Of
      the imaging parameters, MTV at the fixed standardized uptake value threshold of
      2.0 (MTV(2.0)) most accurately predicted metastasis by receiver-operating
      characteristic curve analysis (area under the curve = 0.679, P = 0.011). By
      multivariate analysis, MTV(2.0) > 105 mL (relative risk, 3.93; 95% confidence
      interval, 1.55-9.92) and poor response to neoadjuvant chemotherapy (relative
      risk, 4.83; 95% confidence interval, 1.64-14.21) independently shortened
      metastasis-free survival (P = 0.004 for both parameters). The stratification of
      patients by the combined criteria of MTV(2.0) and histologic response predicted
      outcome in more detail. CONCLUSION: MTV is an independent predictor of metastasis
      in patients with osteosarcoma of the extremities. The combination of MTV and
      histologic response predicts survival more accurately than the chemotherapeutic
      response alone.

PMID- 23949910
TI  - 18F-ICMT-11, a caspase-3-specific PET tracer for apoptosis: biodistribution and
      radiation dosimetry.
AB  - Effective anticancer therapy induces tumor cell death through apoptosis.
      Noninvasive monitoring of apoptosis during therapy may provide predictive outcome
      information and help tailor treatment. A caspase-3-specific imaging radiotracer,
      (18)F-(S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl)methyl)-5-(2(2,4
      difluorophenoxymethyl)-pyrrolidine-1-sulfonyl)isatin ((18)F-ICMT-11), has been
      developed for use in PET studies. We report the safety, biodistribution, and
      internal radiation dosimetry profiles of (18)F-ICMT-11 in 8 healthy human
      volunteers. METHODS: (18)F-ICMT-11 was intravenously administered as a bolus
      injection (mean +/- SD, 159 +/- 2.75 MBq; range, 154-161 MBq) to 8 healthy
      volunteers (4 men, 4 women). Whole-body (vertex to mid thigh) PET/CT scans were
      acquired at 6 time points, up to 4 h after tracer injection. Serial whole blood,
      plasma, and urine samples were collected for radioactivity measurement and
      radiotracer stability. In vivo (18)F activities were determined from quantitative
      analysis of the images, and time-activity curves were generated. The total
      numbers of disintegrations in each organ normalized to injected activity
      (residence times) were calculated as the area under the curve of the time
      activity curve, normalized to injected activities and standard values of organ
      volumes. Dosimetry calculations were then performed using OLINDA/EXM 1.1.
      RESULTS: Injection of (18)F-ICMT-11 was well tolerated in all subjects, with no
      serious tracer-related adverse events reported. The mean effective dose averaged
      over both men and women was estimated to be 0.025 +/- 0.004 mSv/MBq (men, 0.022
      +/- 0.004 mSv/MBq; women, 0.027 +/- 0.004 mSv/MBq). The 5 organs receiving the
      highest absorbed dose (mGy/MBq), averaged over both men and women, were the
      gallbladder wall (0.59 +/- 0.44), small intestine (0.12 +/- 0.05), upper large
      intestinal wall (0.08 +/- 0.07), urinary bladder wall (0.08 +/- 0.02), and liver
      (0.07 +/- 0.01). Elimination was both renal and via the hepatobiliary system.
      CONCLUSION: (18)F-ICMT-11 is a safe PET tracer with a dosimetry profile
      comparable to other common (18)F PET tracers. These data support the further
      development of (18)F-ICMT-11 for clinical imaging of apoptosis.

PMID- 23949911
TI  - PulmoBind, an adrenomedullin-based molecular lung imaging tool.
AB  - Previous studies showed that adrenomedullin (AM) could be a promising agent for
      molecular imaging of the pulmonary circulation, with abundant specific binding
      sites at the pulmonary vascular endothelium. The purpose of this work was to
      design an AM-based compound that encompasses the desired imaging properties
      without posing safety issues for clinical applications. METHODS: AM analogs were
      synthesized through solid-phase peptide synthesis. They were evaluated for
      (99m)Tc labeling efficiency and in vivo lung uptake. Biodistribution and
      hemodynamic characteristics of the lead compound were determined in anesthetized
      dogs as well as by a dosimetric analysis. Lung perfusion was evaluated in the
      monocrotaline model of pulmonary arterial hypertension in rats. RESULTS: A cyclic
      AM (residues 22-52) analog encompassing a polyethylene glycol spacer and a
      tetrapeptide chelating moiety was found to possess the desired characteristics,
      with 90.7% +/- 0.3% (mean +/- SD) labeling efficiency, 40% lung uptake at 10 min
      after injection, and a favorable safety profile. Lung uptake of the (99m)Tc
      labeled compound was markedly reduced in rats with pulmonary arterial
      hypertension. CONCLUSION: This lead compound could be a suitable clinical imaging
      agent for the molecular diagnosis of disorders of the pulmonary circulation.

PMID- 23949912
TI  - Analysis of red blood cell deformation under fast shear flow for better
      estimation of hemolysis.
AB  - We examined the deformation behavior of a red blood cell (RBC) in various flow
      fields to determine whether the extent of RBC deformation is correlated with the
      shear stress used as a hemolysis index. The RBC model was introduced to a simple
      shear flow (Couette flow) and to slightly complex flows (unsteady shear flows and
      stenosed flows). The RBC deformation was assessed by the maximum first principal
      strain over the RBC membrane and compared with the shear stress. Although the
      results were consistent under steady Couette flow, this was not the case under
      unsteady Couette flow or stenosed flow due to the viscoelastic nature of the RBC
      deformation caused by fluid forces. These results suggest that there is a
      limitation in accurately estimating the mechanical damage of RBCs solely from a
      macroscopic flow field, indicating the necessity of taking into account the
      dynamic deformation of RBCs to provide a better estimation of hemolysis.

PMID- 23949913
TI  - Boston type craniosynostosis: report of a second mutation in MSX2.
AB  - We describe a family that segregated an autosomal dominant form of
      craniosynostosis characterized by variable expression and limited extra-cranial
      features. Linkage analysis and genome sequencing were performed to identify the
      underlying genetic mutation. A c.443C>T missense mutation in MSX2, which predicts
      p.Pro148Leu was identified and segregated with the disease in all affected family
      members. One other family with autosomal dominant craniosynostosis (Boston type)
      has been reported to have a missense mutation in MSX2. These data confirm that
      missense mutations altering the proline at codon 148 of MSX2 cause dominantly
      inherited craniosynostosis.

PMID- 23949914
TI  - Role of DNMT3A, TET2, and IDH1/2 mutations in pre-leukemic stem cells in acute
      myeloid leukemia.
AB  - Aberrant changes in the epigenome are now recognized to be important in driving
      the development of multiple human cancers including acute myeloid leukemia.
      Recent advances in sequencing technologies have led to the identification of
      recurrent mutations in genes that regulate DNA methylation including DNA
      methyltransferase 3A (DNMT3A), ten-eleven translocation 2 (TET2), and isocitrate
      dehydrogenase 1 (IDH1) and IDH2. These mutations have been shown to promote self
      renewal and block differentiation of hematopoietic stem/progenitor cells.
      Acquisition of these mutations in hematopoietic stem cells can lead to their
      clonal expansion resulting in a pre-leukemic stem cell (pre-LSC) population. Pre
      LSCs retain the ability to differentiate into the full spectrum of mature
      daughter cells but can become fully transformed with the acquisition of
      additional driver mutations. Here, we review the effects of mutations in DNMT3A,
      TET2, and IDH1/2 on mouse and human hematopoiesis, the current understanding of
      their role in pre-LSCs, and therapeutic strategies to eliminate this population
      which may serve as a cellular reservoir for relapse. 

PMID- 23949915
TI  - Clinical manifestation of angioimmunoblastic T-cell lymphoma with exuberant
      plasmacytosis.
AB  - Angioimmunoblastic T-cell lymphoma (AITL) is a rare subtype of non-Hodgkin
      lymphoma characterized by aggressive symptoms and various abnormal laboratory
      test results. One of the rare immunologic abnormalities in AITL is exuberant
      polyclonal plasmacytosis, but its clinical significance has not been evaluated.
      This report concerns three AITL cases with exuberant polyclonal plasmacytosis and
      investigates its clinical impact by comparison with 12 patients without
      plasmacytosis. Our study found that the performance status (PS) of the former was
      significantly worse and their serum immunoglobulin levels were significantly
      higher. All other parameters, including B symptoms, various prognostic scores,
      blood cell counts other than plasmacyte, and serum levels of lactate
      dehydrogenase, C-reactive protein and soluble interleukin-2 receptor, showed no
      significant differences. More importantly, although the diagnosis of AITL with
      plasmacytosis was not straightforward in our series, outcomes of treatment with
      conventional chemotherapy or immunosuppressive therapy with cyclosporine A were
      favorable. To conclude, AITL should be considered a candidate underlying disease
      of exuberant polyclonal plasmacytosis. Provided a correct diagnosis is made early
      and is followed by adequate treatment, the prognosis for AITL with plasmacytosis
      may not be worse than that for those without plasmacytosis despite the severe
      exhaustion at first presentation. 

PMID- 23949917
TI  - Sonographic findings of pure ductal carcinoma in situ.
AB  - PURPOSE: To investigate the characteristic sonographic (US) findings of pure
      ductal carcinoma in situ (DCIS) in a large series. METHODS: We retrospectively
      reviewed the US findings of 126 cases of pure DCIS in 123 consecutive patients
      who underwent surgery for breast cancer in our hospital. We analyzed the US
      findings of the lesions according to mass or nonmass abnormality, shape, margin,
      orientation, echogenicity, echotexture, boundary echo, posterior acoustic
      features, presence of associated ductal dilatation, presence of intralesional
      cystic focus, and presence of microcalcifications on US. We compared the US
      characteristics of pure DCIS with and without mammographic microcalcifications.
      RESULTS: Seventy-eight cases of pure DCIS had microcalcifications and 48 had no
      microcalcifications on mammography (MG). Overall, 109 cases (86.5%) of pure DCIS
      were demonstrated on US. DCIS with microcalcifications on MG showed positive US
      findings in 79.5% of cases. The most common US finding was heterogeneous hyper-
      or isoechoic parenchyma with intralesional microcalcifications and without
      posterior acoustic features. DCIS without microcalcifications on MG showed
      positive US findings in 97.9% of cases. The most common US findings were masses
      with round or oval shape, microlobulated margin, parallel orientation,
      heterogeneous mild hypoechogenicity, and without boundary echo or posterior
      acoustic features. Ductal dilatations and intralesional cystic foci were present
      in 17.5% (22/126) and 23.8% (30/126) of pure DCIS, respectively. CONCLUSIONS:
      Overall, US could demonstrate 85.7% of pure DCIS cases, including 16 (12.7%)
      cases of clinically and mammographically occult pure DCIS. DCIS with and without
      microcalcifications on MG showed different US characteristics.

PMID- 23949916
TI  - Role of non-HLA gene polymorphisms in graft-versus-host disease.
AB  - A large number of reports have associated various non-HLA gene polymorphisms with
      the risk and severity of graft-versus-host disease (GVHD). To date, candidate
      gene studies and genome-wide association studies have been performed to
      investigate such non-HLA gene polymorphisms in relation to GVHD. Candidate gene
      studies are hypothesis-driven and cost-effective, whereas genome-wide association
      studies have the potential to discover new gene polymorphisms, including possible
      biomarkers and therapeutic targets. Some gene polymorphisms have the potential to
      affect protein function or gene expression, or to encode minor histocompatibility
      antigens. Non-HLA genotyping for genes influencing GVHD prior to transplantation
      should provide useful information that will facilitate choosing the donor, type
      of graft, conditioning treatment, and GVHD prophylaxis. However, attention should
      be paid to the need for validation studies and ethical issues. 

PMID- 23949918
TI  - Lipid-modulating treatments for mixed dyslipidemia increase HDL-associated
      phospholipase A2 activity with differential effects on HDL subfractions.
AB  - The effect of lipid-modulating treatments on modification of high density
      lipoprotein (HDL) subfractions remains unknown. In this study, mixed dyslipidemia
      patients (n = 100) inadequately controlled with a standard statin dose were
      randomized to switch to 40 mg of rosuvastatin or add-on extended release
      nicotinic acid/laropiprant (ER-NA/LRPT) or add-on fenofibrate. The cholesterol
      concentrations of HDL (HDL-C) subfractions and HDL-associated lipoprotein
      associated phospholipase A2 (HDL-Lp-PLA2) activity were assessed at baseline and
      3 months later. We observed that large HDL-C increased by 50 and 6 % in the add
      on-ER-NA/LRPT and rosuvastatin groups, respectively, while it decreased by 20 %
      in the add-on-fenofibrate group (p < 0.01 vs baseline for all groups and p < 0.01
      for all comparisons among groups). On the other hand, small HDL-C decreased by 17
      % in the add-on-ER-NA/LRPT group (p < 0.01 vs baseline), while it increased by 25
      % in the add-on-fenofibrate group (p < 0.01 vs baseline) without any change in
      the rosuvastatin group (p < 0.01 for all comparisons among groups). HDL-Lp-PLA2
      activity increased by 55, 33 and 18 % in add-on-ER-NA/LRPT, add-on-fenofibrate
      and rosuvastatin groups, respectively (p < 0.01 for all comparisons vs baseline
      and for all comparisons among groups). In conclusion, add-on-ER-NA/LRPT was
      associated with an increase in large HDL-C and a decrease in small HDL-C, while
      opposite effects were noticed in the add-on-fenofibrate group. Add-on-ER-NA/LRPT
      was associated with the most pronounced increase in HDL-Lp-PLA2 activity. 

PMID- 23949919
TI  - EPA and DHA levels in whole blood decrease more rapidly when stored at -20 
      degrees C as compared with room temperature, 4 and -75  degrees C.
AB  - High-throughput n-3 fatty acid profiling is enabled by collection techniques such
      as venous whole blood and fingertip prick (FTP) sampling, but the resulting
      increased sample numbers increases storage demand. Highly unsaturated fatty acids
      (HUFA) in erythrocytes are susceptible to oxidation, but this tendency is poorly
      characterized in venous and FTP whole blood. Presently, whole blood samples with
      low and high n-3 content collected with ethylenediaminetetraacetic acid were
      stored on chromatography paper with and without BHT pre-treatment for up to 180
      days at different temperatures (room, 4, -20, -75  degrees C). Whole blood
      prepared with heparin and BHT and stored in cryovials was also examined.
      Eicosapentaenoic acid (EPA, 20:5n-3) + docosahexaenoic acid (DHA, 22:6n-3) is
      relatively stable when stored at -75  degrees C under various conditions but
      rapidly decreases in whole blood when stored at -20  degrees C. At -20  degrees
      C, BHT + heparin prepared whole blood can prevent decreases in cryovials up to
      180 days but BHT only slows the decreases on chromatography paper. Surprisingly,
      whole blood stored at 4  degrees C and room temperature was less susceptible to
      decreases in EPA + DHA as compared with -20  degrees C storage. Assessments of n
      3 blood biomarkers indicate the % n-3 HUFA in total HUFA was more stable as
      compared with the sum of the relative % of EPA + DHA. In conclusion, FTP and
      venous whole blood for fatty acid analysis should be stored at -75  degrees C
      whenever possible. In the absence of -75  degrees C storage conditions, BHT
      should be added and 4  degrees C or room temperature appear to be better
      alternatives to -20  degrees C. 

PMID- 23949920
TI  - Nuclear localization of the transcriptional coactivator YAP is associated with
      invasive lobular breast cancer.
AB  - BACKGROUND: Yes Associated Protein (YAP) has been implicated in the control of
      organ size by regulating cell proliferation and survival. YAP is a
      transcriptional coactivator that controls cellular responses through interaction
      with TEAD transcription factors in the nucleus, while its transcriptional
      functions are inhibited by phosphorylation-dependent translocation to the
      cytosol. YAP overexpression has been associated with different types of cancer,
      such as lung, skin, prostate, ovary and liver cancer. Recently, YAP was linked to
      E-cadherin-dependent regulation of contact inhibition in breast cancer cells.
      RESULTS: In this study we examined YAP protein expression and cellular
      localization in 237 cases of human invasive breast cancer by immunohistochemistry
      and related its expression to clinicopathological features and E-cadherin
      expression. We observed that invasive lobular carcinoma is characterized by
      higher expression levels of both nuclear and cytosolic YAP (p < 0.001). Nuclear
      YAP expression did not associate with other variables such as lymph node
      involvement, tumor grade, tumor size, mitotic activity or the molecular sub-types
      of invasive breast cancer. We observed that high nuclear and cytosolic YAP
      expression are associated with the E-cadherin deficient breast cancer subtype ILC
      (p < 0.001) and cell lines derived from human breast cancers and conditional
      mouse models of human lobular breast cancer. CONCLUSIONS: Since our data indicate
      that nuclear YAP localization is more common in breast cancers lacking functional
      adherens junctions, it suggests that YAP-mediated transcription may be involved
      in the development and progression of invasive lobular breast cancer.

PMID- 23949922
TI  - Retraction.

PMID- 23949921
TI  - Effect of race on left ventricular ejection fraction decline after initial
      improvement with beta blockers in patients with non-ischemic cardiomyopathy: a
      retrospective analysis.
AB  - BACKGROUND: Although beta blockers (BBs) are established therapy in heart
      failure, some patients whose left ventricular ejection fraction (LVEF) initially
      increases on BB therapy experience a subsequent LVEF decline. This study aimed to
      evaluate the proportion of patients with non-ischemic cardiomyopathy (NICM) whose
      LVEF declines while on BB therapy and determine important predictors of LVEF
      decline. METHODS: A retrospective analysis of 238 patients receiving a BB
      (carvedilol, metoprolol succinate, or tartrate), with an ejection fraction of
      <=40% and NICM, whose LVEF initially rose >=5% after 1 year of BB therapy, was
      conducted. Post-response LVEF decline >=5% to a final LVEF of <=35% was evaluated
      within 4 years of BB initiation. RESULTS: In our study, we had 52 Caucasians
      (22%), 78 Hispanics (33%), and 108 African Americans (45%). Overall, 32 patients
      (13.44 %) had post-response LVEF decline. The nadir LVEF of patients with post
      response LVEF decline was 25% (interquartile range 20-27). Compared with others,
      Hispanics had lower nadir LVEF (22%, p < 0.001). Important predictors of LVEF
      decline were Hispanic race (odds ratio (OR) 6.094, p < 0.001), New York Heart
      Association (NYHA) class (OR 2.287, p < 0.05), baseline LVEF (OR 1.075, p <
      0.05), and age (OR 0.933, p < 0.001). CONCLUSION: A significant proportion
      (13.44%) of NICM patients with LVEF increase over 1 year of BB therapy
      experienced subsequent LVEF decline. Race, NYHA class, baseline LVEF, and age are
      important predictors of this decline.

PMID- 23949924
TI  - Survival of trisomy 18 (Edwards syndrome) and trisomy 13 (Patau Syndrome) in
      England and Wales: 2004-2011.
AB  - The aim of this study is to determine the survival of live births with trisomy 18
      and trisomy 13 and their variants. Information on live births with trisomy 18 or
      trisomy 13 recorded in the National Down Syndrome Cytogenetic Register (NDSCR)
      was linked by the NHS Information Centre to obtain information about survival.
      Survival was known for 326 (88%) of live births with trisomy 18 and 142 (82%) of
      live births with trisomy 13 born in England and Wales between 2004 and 2011. The
      median survival time for live births with full trisomy 18 was 14 days and with
      full trisomy 13 was 10 days, the 3-month survival was 20% and 18%, respectively,
      and the 1-year survival for both syndromes was 8%. The 1-year survival for live
      births with trisomy 18 mosaicism (n = 17) was 70%, for those with trisomy 13
      mosaicism (n = 5) was 80% and for those with partial trisomy 13 (Robertsonian
      translocations) (n = 17) was 29%. This study is based on the largest data set on
      survival for live births with trisomy 18 and trisomy 13. Although median survival
      for these children is 2 weeks or less, about one in five survive for 3 months or
      more and about 1 in 12 survive for 1 year or more. We suggest that these survival
      rates are used in counselling as well as the median survival time.

PMID- 23949925
TI  - Sonographic examination of the buttock.
AB  - The buttock is a common site of pathology and ultrasound and is often the first
      line imaging modality to examine soft tissue lesions of the buttock region. This
      review describes the ultrasound technique used, the relevant ultrasound anatomy,
      and the sonographic appearances of common and uncommon pathological conditions
      found in the buttock region.

PMID- 23949926
TI  - Applicability to foraging simulation of a reinforcement schedule controlling the
      response energy of pigeons.
AB  - In optimal foraging theory (OFT), energy expenditure is an important variable for
      predicting foraging behavior. However, early studies, including operant
      simulations of foraging, did not measure energy expenditure. In the present
      study, an adjusting energy (AE) schedule was developed to control energy
      expenditure. Interresponse energy (IRE), a measure of the energy expenditure
      during a response, was calculated by dividing the square of the elapsed time
      between two consecutive responses by the square of the straight-line distance
      between the locations of the same two responses. An adjusting procedure was
      employed to estimate the indifference point between the requirements of the AE
      schedule and a fixed ratio (FR) schedule, which has been used in many operant
      simulations. In the adjusting procedure, pigeons adjusted the requirement of the
      AE schedule to that of the FR schedule. The results showed a systematic
      relationship between the requirements of the AE and FR schedules. Moreover, the
      total IRE per reinforcement systematically increased with the AE requirement.
      Thus, the present study demonstrates the utility of the AE schedule as a
      procedure for testing the validity of OFT. 

PMID- 23949927
TI  - Alternatives to seclusion and restraint in psychiatry and in long-term care
      facilities for the elderly: perspectives of service users and family members.
AB  - BACKGROUND: There is growing interest in involving patients in decisions
      regarding healthcare technologies. This research project was conducted in
      collaboration with decision makers and health technology assessment agents in
      order to involve healthcare service users (and their loved ones) in the
      assessment of alternatives to seclusion and restraint in short-term psychiatric
      wards and long-term care facilities for the elderly. OBJECTIVE: This paper
      explores the viewpoints and suggestions of service users and service users'
      families about alternatives to restraint and seclusion, as well as conditions
      under which they could be used among adults in short-term psychiatric care and
      residents in long-term care facilities. METHODS: Using a semi-structured guide,
      we held eight focus groups: five with mental health service users and three with
      family members of elderly people in long-term care facilities. Focus group
      discussions were digitally recorded and transcribed verbatim, and we performed
      content analysis using NVivo 8 software. RESULTS: In both care environments,
      participants emphasized the importance of communicating with service users, as
      well as assessing their needs and their particular situation, for reducing the
      use of restraint and seclusion. A better welcome and accompaniment of people
      admitted for short-term psychiatric care emerged also as key approaches to reduce
      the use of restraint and seclusion. Long-term care facilities could also reduce
      the need for restraint and seclusion by creating a stimulating home environment
      and individualized occupational therapy programs. Participants in both groups
      suggested that caregivers other than healthcare staff could be more involved,
      especially peer-support workers in the case of psychiatric care and volunteers in
      the case of long-term care facilities. CONCLUSION: Participants suggested that
      changes were needed at a broader and more systemic level than simply replacing
      current measures of restraint and seclusion with alternative techniques. They
      favored an approach focused more on the person than on the techniques: they
      suggested that listening to and communicating with the service user could reduce
      the use of restraint and seclusion in both healthcare environments.

PMID- 23949929
TI  - MRI diffusion-weighted imaging (DWI) in pediatric small bowel Crohn disease:
      correlation with MRI findings of active bowel wall inflammation.
AB  - BACKGROUND: Restricted diffusion on diffusion-weighted imaging (DWI) sequences
      during magnetic resonance enterography (MRE) has been shown in segments of bowel
      affected by Crohn disease. However, the exact meaning of this finding,
      particularly within the pediatric Crohn disease population, is poorly understood.
      OBJECTIVE: The purpose of this study was to determine the significance of bowel
      wall restricted diffusion in children with small bowel Crohn disease by
      correlating apparent diffusion coefficient (ADC) values with other MRI markers of
      disease activity. MATERIALS AND METHODS: A retrospective review of pediatric
      patients (<= 18 years of age) with Crohn disease terminal ileitis who underwent
      MRE with DWI at our institution between May 1, 2009 and May 31, 2011 was
      undertaken. All of the children had either biopsy-proven Crohn disease terminal
      ileitis or clinically diagnosed Crohn disease, including terminal ileal
      involvement by imaging. The mean minimum ADC value within the wall of the
      terminal ileum was determined for each examination. ADC values were tested for
      correlation/association with other MRI findings to determine whether a
      relationship exists between bowel wall restricted diffusion and disease activity.
      RESULTS: Forty-six MRE examinations with DWI in children with terminal ileitis
      were identified (23 girls and 23 boys; mean age, 14.3 years). There was
      significant negative correlation or association between bowel wall minimum ADC
      value and established MRI markers of disease activity, including degree of bowel
      wall thickening (R = (-)0.43; P = 0.003), striated pattern of arterial
      enhancement (P = 0.01), degree of arterial enhancement (P = 0.01), degree of
      delayed enhancement (P = 0.045), amount of mesenteric inflammatory changes (P <
      0.0001) and presence of a stricture (P = 0.02). ADC values were not significantly
      associated with bowel wall T2-weighted signal intensity, length of disease
      involvement or mesenteric fibrofatty proliferation. CONCLUSION: Increasing bowel
      wall restricted diffusion (lower ADC values) is associated with multiple MRI
      findings that are traditionally associated with active inflammation in pediatric
      small bowel Crohn disease.

PMID- 23949931
TI  - Long head of the biceps tendon and rotator interval.
AB  - The term "biceps brachii" is a Latin phrase meaning "two-headed (muscle) of the
      arm." As its name suggests, this muscle has two separate origins. The short head
      of biceps is extraarticular in location, originates from the coracoid process of
      the scapula, having a common tendon with the coracobrachialis muscle. The long
      head of biceps tendon (LBT) has a much more complex course, having an
      intracapsular and an extracapsular portion. The LBT originates from the
      supraglenoid tubercle, and in part, from the glenoid labrum; the main labral
      attachments vary arising from the posterior, the anterior of both aspects of the
      superior labrum (Bletran et al. in Top Magn Reson Imaging 14:35-49, 2003;
      Vangsness et al. in J Bone Joint Surg Br 76:951-954, 1994). Before entering the
      bicipital groove (extracapsular portion), the LBT passes across the "rotator cuff
      interval" (intracapsular portion). Lesions of the pulley system, the LBT, and the
      supraspinatus tendon, as well as the subscapularis, are commonly associated
      (Valadie et al. in J Should Elbow Surg 9:36-46, 2000). The pulley lesion can be
      caused by trauma or degenerative changes (LeHuec et al. in J Should Elbow Surg
      5:41-46, 1996). MR arthrography appears to be a promising imaging modality for
      evaluation of the biceps pulley, through the distention of the capsule of the
      rotator interval space and depiction of the associated ligaments.

PMID- 23949932
TI  - Imaging assessment of groin pain.
AB  - Groin pain is a common condition in athletes, especially those who play certain
      sports, for instance soccer, ice hockey, fencing which request rapid acceleration
      and frequent changes of movement. This condition represents a diagnostic
      difficulty for the radiologist due to either the anatomical pubic region
      complexity than the many causes that can be a source of pain, because the groin
      pain can be determined by conditions affecting the bony structures, cartilage and
      muscle tendons that are part of the proper pubis but also from those involving
      the hip. The approach to the groin through diagnostic imaging is
      multidisciplinary: The study of the patient is performed by traditional
      radiographs, ultrasound examination, magnetic resonance imaging or computed
      tomography, based on clinical suspicion, and each of these methods provides
      different results depending on the disease in question. The purpose of this
      article is to examine what are the optimal imaging techniques to investigate the
      various diseases affecting the patient with groin pain.

PMID- 23949933
TI  - Femoroacetabular impingement: role of imaging.
AB  - The femoroacetabular impingement (FAI) is an impingement characterized by
      repetitive abutment between the femur and the acetabular rim during hip motion
      due to loss of joint clearance (Imam and Khanduja in Int Orthop 35(10):1427-1435,
      2011; James et al. in AJR Am J Roentgenol 187(6):1412-1419, 2006).
      Femoroacetabular impingement (FAI) can be classified as either cam or pincer
      type, and it can be differentiated on the basis of a predominance of either a
      femoral or an acetabular abnormality (Pfirrmann et al. in Radiology 244(2):626,
      2007; Ganz et al. in Clin Orthop Relat Res 466(2):264-272, 2008). In cases of cam
      FAI, the nonspherical shape of the femoral head at the femoral head-neck junction
      and reduced depth of the femoral waist lead to abutment of the femoral head-neck
      junction against the acetabular rim. In cases of pincer FAI, acetabular
      overcoverage limits the range of motion and leads to a conflict between the
      acetabulum and the femur. The most important role of preoperative MR evaluation
      in patients affected by FAI is the accurate assessment of the damage's extension.

PMID- 23949934
TI  - Mechanism of traumatic knee injuries and MRI findings.
AB  - Bone bruises are focal abnormalities in subchondral bone marrow due to trabecular
      microfractures as a result of traumatic force. These trauma-induced lesions are
      better detected with magnetic resonance (MR) imaging using water-sensitive
      sequences. Moreover, the pattern of bone bruise is distinctive and allows us to
      understand the dynamics of trauma and to predict associated soft injuries. This
      article discusses the mechanism of traumatic injury and MR findings. 

PMID- 23949935
TI  - Financial impact of radiological reports on medical-legal evaluation of
      compensation for meniscal lesions.
AB  - To evaluate any discrepancy between radiological reports for clinical purposes
      and for medicolegal purposes and to quantify its economic impact on repayments
      made by private insurance companies for meniscal injuries of the knee. The
      medical records obtained pertaining to 108 knee injury patients (mean age 43.3
      years) assessed over a period of 12 months were analysed. Clinical medical
      reports, aimed at assessing the lesion, and medicolegal reports, drawn up with a
      view to quantifying compensation, were compared. Unlike reports for clinical
      purposes in reports for medicolegal purposes, in the evaluation of meniscal
      lesions, in addition to morphological features of lesions, chronological,
      topographical, severity and exclusion criteria were applied. To estimate the
      economic impact resulting from the biological damage, we consulted an actuarial
      table based on the 9-point minor incapacity classification system. Meniscal
      lesions not compatible with a traumatic event and therefore not eligible for an
      insurance payout were found in 56 patients. Of these, 37 failed exclusion
      criteria, while 19 failed to meet chronological criteria. This difference
      resulted in a reduction in compensation made by private insurance companies with
      savings estimated with a saving between euro 203,715.41 and euro 622,315.39. The
      use of a clinical report for medicolegal purposes can be a source of valuation
      error, as chronological and/or dynamic information regarding the trauma mechanism
      may be lacking. Therefore, the use of a full radiological appraisal allows a
      better damage's assessment and an adequate compensation for injuries.

PMID- 23949936
TI  - Diagnostic imaging of ankle impingement syndromes in athletes.
AB  - The chronic ankle pain is a very frequent clinical problem, which is often
      characterized by a painful mechanical limitation of full-range ankle movement. A
      large amount of causes are involved in its pathogenesis, but the most common
      forms are secondary to an osseous or soft tissue abnormality. Especially for
      professional athletes, impingement lesions are the most important causes of
      chronic pain; however, this symptomatology can also affect ordinary people,
      mostly in those who work in environments that cause severe mechanical stress on
      the joints. This group of pathologies is characterized by a joint conflict
      secondary to an abnormal contact among bone surfaces or between bones and soft
      tissues. Diagnosis is mainly clinic and secondly supported by imaging in order to
      localize the critical area of impingement and determine the organic cause
      responsible for the joint conflict. Treatments for different forms of impingement
      are similar. Usually, the first step is a conservative approach (rest,
      physiotherapy, ankle bracing, shoe modification and local injection of
      corticosteroids), and only in case of unsuccessful response, the second step is
      the operative treatment with open and arthroscopic techniques. The aim of the
      study is to describe different MR imaging patterns, comparing our data with those
      reported in the literature, in order to identify the best accurate diagnostic
      protocol. 

PMID- 23949937
TI  - Ankle fracture: radiographic approach according to the Lauge-Hansen
      classification.
AB  - Ankle fractures account for 9 % of fractures (Clare in Foot Ankle Clin 13(4):593
      610, 1) representing a significant portion of the trauma workload; proximal
      femoral fractures are the only lower limb fracture to present more frequently.
      Ankle fractures have a bimodal age distribution with peaks in younger males and
      older females (Arimoto and Forrester in AJR Am J Roentgenol 135(5):1057-1063, 2).
      There has been threefold increase in the incidence among elderly females over the
      past three decades (Haraguchi and Armiger in J Bone Joint Surg Am 91(4):821-829,
      3). In 1950, Lauge-Hansen devised a classification of ankle fractures based on
      the position of the foot and the deforming force at the time of injury. This has
      been widely accepted by orthopedists, but is not in general use by radiologists.
      Identification of the fractures and classification of the type of injury allows
      diagnosis of the otherwise occult ligamentous injuries. Three radiographic views
      of the ankle (anteroposterior, mortise, and lateral) are necessary to classify an
      injury with the Lauge-Hansen system. Two additional criteria are also necessary:
      the position of the foot at the time of injury and the direction of the deforming
      force.

PMID- 23949938
TI  - Ankle impingement: a review of multimodality imaging approach.
AB  - Ankle impingement is defined as entrapment of an anatomic structure that leads to
      pain and decreased range of motion of the ankle and can be classified as either
      soft tissue or osseous (Bassett et al. in J Bone Joint Surg Am 72:55-59, 1990).
      The impingement syndromes of the ankle are a group of painful disorders that
      limit full range of movement. Symptoms are due to compression of soft-tissues or
      osseous structures during particular movements (Ogilvie-Harris et al. in
      Arthroscopy 13:564-574, 1997). Osseous impingement can result from spur formation
      along the anterior margin of the distal tibia and talus or as a result of a
      prominent posterolateral talar process, the os trigonum. Soft-tissue impingement
      usually results from scarring and fibrosis associated with synovial, capsular, or
      ligamentous injury. Soft-tissue impingement most often occurs in the
      anterolateral gutter, the medial ankle, or in the region of the syndesmosis (Van
      den Bekerom and Raven in Knee Surg Sports Traumatol Arthrosc 15:465-471, 2007).
      The main impingement syndromes are anterolateral, anterior, anteromedial,
      posterior, and posteromedial impingement. These conditions arise from initial
      ankle injuries, which, in the subacute or chronic situation, lead to development
      of abnormal osseous and soft-tissue thickening within the ankle joint. The
      relative contributions of the osseous and soft-tissue abnormalities are variable,
      but whatever component is dominant there is physical impingement and painful
      limitation of ankle movement. Conventional radiography is usually the first
      imaging technique performer and allows assessment of any potential bone
      abnormality, particularly in anterior and posterior impingement. Computed
      tomography (CT) and isotope bone scanning have been largely superseded by
      magnetic resonance (MR) imaging. MR imaging can demonstrate osseous and soft
      tissue edema in anterior or posterior impingement. MR imaging is the most useful
      imaging modality in evaluating suspected soft-tissue impingement or in excluding
      other ankle pathology such as an osteochondral lesion of the talus. MR imaging
      can reveal evidence of previous ligamentous injury and also can demonstrate
      thickened synovium, fibrosis, or adjacent reactive soft-tissue edema. Studies of
      conventional MR imaging have produced conflicting sensitivities and specificities
      in assessment of anterolateral impingement. CT and MR arthrographic techniques
      allow the most accurate assessment of the capsular recesses, albeit with
      important limitations in diagnosis of clinical impingement syndromes. In the
      majority of cases, ankle impingement is treated with conservative measures, with
      surgical debridement via arthroscopy or an open procedure reserved for patients
      who have refractory symptoms. In this article, we describe the clinical and
      potential imaging features, for the four main impingement syndromes of the ankle:
      anterolateral, anterior, anteromedial, posterior, and posteromedial impingement.

PMID- 23949939
TI  - Atraumatic vertebral compression fractures: differential diagnosis between benign
      osteoporotic and malignant fractures by MRI.
AB  - Atraumatic vertebral compression fractures are a common clinical problem,
      especially in elderly population. Metastases are the most frequent source of bone
      tumors, and the spine is a common site of metastatic disease; in case of cortical
      involvement or osteolysis, they may result in pathological compression fractures.
      Atraumatic compression fractures may result from other primary neoplasms of
      vertebrae and also from osteomyelitis, Paget's disease, hyperparathyroidism and
      other metabolic processes. Osteoporosis is a common source of vertebral
      compression fractures in elderly population, which may be indistinguishable from
      those of metastatic origin. The differentiation between osteoporotic compression
      fractures and malignant fracture is necessary to establish an appropriate staging
      and a therapeutic planning, especially in the acute and subacute stages.
      Anamnestic data about preexisting disease can be useful to individuate the
      potential cause of vertebral collapse. Plain radiography shows some difficulties
      in distinguishing whether the fracture represents a consequence of osteoporosis,
      a metastatic lesion or some other primary bone neoplasm. Computed tomography is
      one of the most suitable imaging techniques for the evaluation of bone structure
      and fragments and to establish the degree of cortical bone destruction; MR
      imaging (MRI) is the most helpful radiological investigation in order to provide
      the basis for the distinction between metastatic and acute osteoporotic
      compression fractures. The most relevant MRI findings to establish a differential
      diagnosis are described.

PMID- 23949940
TI  - Magnetic resonance imaging in brachial plexus injury.
AB  - Brachial plexus injury represents the most severe nerve injury of the
      extremities. While obstetric brachial plexus injury has showed a reduction in the
      number of cases due to the improvements in obstetric care, brachial plexus injury
      in the adult is an increasingly common clinical problem. The therapeutic measures
      depend on the pathologic condition and the location of the injury: Preganglionic
      avulsions are usually not amenable to surgical repair; function of some
      denervated muscles can be restored with nerve transfers from intercostals or
      accessory nerves and contralateral C7 transfer. Postganglionic avulsions are
      repaired with excision of the damaged segment and nerve autograft between nerve
      ends or followed up conservatively. Magnetic resonance imaging is the modality of
      choice for depicting the anatomy and pathology of the brachial plexus: It
      demonstrates the location of the nerve damage (crucial for optimal treatment
      planning), depicts the nerve continuity (with or without neuroma formation), or
      may show a completely disrupted/avulsed nerve, thereby aiding in nerve-injury
      grading for preoperative planning. Computed tomography myelography has the
      advantage of a higher spatial resolution in demonstration of nerve roots compared
      with MR myelography; however, it is invasive and shows some difficulties in the
      depiction of some pseudomeningoceles with little or no communication with the
      dural sac. 

PMID- 23949941
TI  - Rehabilitation and surgical management of ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory disease which, if
      untreated, may progress to severe damage of the spine with functional impairment,
      disability and poor quality of life. An increased mortality has been reported in
      AS patients compared to the general population. AS requires combined management
      (pharmacological and non-pharmacological) and advice by different health
      professionals. Even the pharmacological treatment in the last decade has
      dramatically changed the outcome, the severity of the disease might require a
      surgical approach for the hip involvement with total hip replacement, or the
      corrective spinal surgery. However, this surgery deserves some careful approaches
      since the complexity of the disease. Rehabilitation still represents a
      cornerstone of the global management of AS patients. The present review
      summarizes the state of art of surgical management of these two diseases. 

PMID- 23949942
TI  - Lesions of the rotator cuff footprint: diagnostic performance of MR arthrography
      compared with arthroscopy.
AB  - BACKGROUND: To evaluate the diagnostic performance of magnetic resonance
      arthrography (MR-A) of the shoulder in the diagnosis of rotator cuff tears
      involving the humeral insertion of the supraspinatus and infraspinatus tendon
      (footprint), using arthroscopy as the reference standard. MATERIALS AND METHODS:
      The study population included 90 consecutive patients with history and clinical
      diagnosis of instability of the shoulder, rotator cuff tear or posterosuperior
      glenoid impingement. A total of 108 MR arthrograms were performed, since 18
      patients had undergone a bilateral procedure. Arthroscopy, which was performed
      within 45 days after MR-A, was used as the reference standard. Sensitivity,
      specificity, accuracy, positive and negative predictive values were then
      calculated. RESULTS: Magnetic resonance arthrography showed a sensitivity of 92 %
      and a specificity of 78 % for the overall detection of tears involving the
      rotator cuff footprint. The diagnostic accuracy was 90 %, and the positive and
      negative predictive values were 95 and 64 %, respectively. Ten lesions were non
      classifiable on surgery, of which eight were non-classifiable on MR-A also.
      CONCLUSIONS: Magnetic resonance arthrography is extremely accurate for the
      detection and classification of rotator cuff footprint tears. Most of these
      lesions are articular-sided (partial articular-sided supraspinatus tendon
      avulsion lesions) with predominance in younger patients and concealed type of
      tear (concealed interstitial delamination lesions).

PMID- 23949943
TI  - Primary lymphoma of the central nervous system--a diagnostic challenge.
AB  - Primary lymphoma of the central nervous system is a distinct diffuse large B-cell
      lymphoma confined to the nervous system. Whereas classical cases can be
      classified easily, differential diagnosis can be a challenge in particular in
      patients who had received treatment prior to biopsy. In the differential
      diagnosis, other tumours and inflammatory diseases of autoimmune and infectious
      aetiology need to be considered.

PMID- 23949944
TI  - Associative structure of integrated temporal relationships.
AB  - According to the temporal-coding hypothesis (TCH; Savastano & Miller, Behavioural
      Processes 44:147-162, 1998), acquired associations include temporal information
      concerning the interval between the associated elements. Moreover, the TCH posits
      that subjects can integrate two independently acquired associations that share a
      common element (e.g., S2-S1 and S1-US), which results in the creation of a third
      association with its own temporal relationship (S2-US). Some evidence has
      suggested that such temporal integration occurs at the time of testing (Molet,
      Miguez, Cham, & Miller, Journal of Experimental Psychology: Animal Behavior
      Processes 38:369-380, 2012). Here we report two fear-conditioning experiments
      with rats conducted to identify the associative structure of the integrated
      temporal relationship. The goal was to distinguish between two possible
      associative structures that could exist following an initial test on which
      temporal integration occurs: (1) Conditioned responding to S2 on subsequent tests
      could be the result of recurring successive activation of two independently
      learned temporal maps that remain independently stored in memory (i.e., S2-S1
      plus S1-US). (2) Temporal integration at the moment of initial testing could
      result in the formation of a direct S2-US (or S2-response) temporal map.
      Integration was found to occur at test and to produce a new association that was
      independent of associations with the common element (S1). However, the
      associative status of S1 appeared to modulate whether or not the new association
      with S2 was US-specific (S2-US) or directly activated a fear response (S2
      response).

PMID- 23949945
TI  - A 3p interstitial deletion in two monozygotic twin brothers and an 18-year-old
      man: further characterization and review.
AB  - An increasing number of patients with 3p proximal deletions were reported in the
      previous decade, but the region responsible for the main features such as
      intellectual disability (ID) and developmental delay is not yet characterized.
      Here we report on two monozygotic twin brothers of 2 10/12 years and an 18-year
      old man, all three of them displaying severe ID, psychomotoric delay, autistic
      features, and only mild facial dysmorphisms. Array CGH (aCGH), revealed a 6.55 Mb
      de novo interstitial deletion of 3p14.1p14.3 in the twin brothers and a 4.76 Mb
      interstitial deletion of 3p14.1p14.2 in the 18-year-old patient, respectively. We
      compared the malformation spectrum with previous molecularly well-defined
      patients in the literature and in the DECIPHER database (Database of Chromosomal
      Imbalance and Phenotype in Humans using Ensembl Resources;
      http://decipher.sanger.ac.uk/). In conclusion, the deletion of a region
      containing 3p14.2 seems to be associated with a relative concise phenotype
      including ID and developmental delay. Thus, we hypothesize that 3p14.2 is the
      potential core region in 3p proximal deletions. The knowledge of this potential
      core region could be helpful in the genetic counselling of patients with 3p
      proximal deletions, especially concerning their phenotype.

PMID- 23949946
TI  - Boron-doped nanocrystalline diamond microelectrode arrays monitor cardiac action
      potentials.
AB  - The expansion of diamond-based electronics in the area of biological interfacing
      has not been as thoroughly explored as applications in electrochemical sensing.
      However, the biocompatibility of diamond, large safe electrochemical window,
      stability, and tunable electronic properties provide opportunities to develop new
      devices for interfacing with electrogenic cells. Here, the fabrication of
      microelectrode arrays (MEAs) with boron-doped nanocrystalline diamond (BNCD)
      electrodes and their interfacing with cardiomyocyte-like HL-1 cells to detect
      cardiac action potentials are presented. A nonreductive means of structuring
      doped and undoped diamond on the same substrate is shown. The resulting BNCD
      electrodes show high stability under mechanical stress generated by the cells. It
      is shown that by fabricating the entire surface of the MEA with NCD, in patterns
      of conductive doped, and isolating undoped regions, signal detection may be
      improved up to four-fold over BNCD electrodes passivated with traditional
      isolators. 

PMID- 23949947
TI  - Metformin in the treatment of obese children and adolescents at risk of type 2
      diabetes.
AB  - Metformin is the first-line treatment for type 2 diabetes (T2D) in adults,
      children and young people, particularly in obese or overweight patients. Many
      studies have demonstrated that metformin is associated with weight reduction in
      adults and in prevention or delay of T2D onset in those who are at increased
      risk. In 2012, metformin was recommended by the UK National Institute for Health
      and Care Excellence as a treatment option in adults aged 18 years or over, who
      remain at high risk of T2D, despite participation in an intensive lifestyle
      change programme. Prevalence of childhood obesity is increasing and is associated
      with elevated long-term risk of T2D and other adverse cardio-metabolic events;
      however, consensus is lacking on intervention strategies aimed at reducing this
      risk. This article discusses the rationale and evidence for the use of metformin
      in obese children and young people at high risk of T2D.

PMID- 23949948
TI  - Deoxynivalenol affects the composition of the basement membrane proteins and
      influences en route the migration of CD16(+) cells into the intestinal
      epithelium.
AB  - The numerous pores in the basement membrane (BM) of the intestinal villi are
      essential for the communication of enterocytes with cells in the lamina propria,
      an important mechanism for the induction of intestinal immune responses. The
      intestinal epithelial barrier is affected by the mycotoxin deoxynivalenol (DON)
      from both the apical (luminal) and basolateral (serosal) side. The pig is the
      most susceptible species to the anorectic and immune-modulating effects of DON,
      which is most prevalent in crops. We analysed in pigs the effect of DON
      contaminated feed on the composition and perforation of the BM and the presence
      of CD16(+) cells or their dendrites in the epithelium. In addition to in vivo
      experiments, in vitro studies were carried out. Using microarray analyses, the
      effects of DON on IPEC-J2 cells were studied with the focus on the BM. Our in
      vivo results showed in the control pigs: (1) a significant increased pore number
      (p <= 0.001) in the jejunum in comparison to ileum, (2) no difference in the pore
      size, and (3) comparable frequency of intraepithelial CD16(+) cells/dendrites in
      the jejunum and ileum. There was a marked trend that DON feeding increases: (1)
      the pore number in jejunum, and (2) the number of CD16(+) cells/dendrites in the
      epithelium (Tukey-Kramer; p = 0.055 and p = 0.067, respectively). The in vivo
      results were extended with microarray analyses of epithelial cell (IPEC-J2
      cells). The down-regulation of genes like syndecan, fibulin 6 and BM-40 was
      observed. These proteins are important factors in the BM composition and in
      formation of pores. Our results provide evidence that already low basolateral
      concentrations of DON (50 ng/mL) influence the production of the BM protein
      laminin by epithelial cells. Thus, DON affects the composition of the BM. 

PMID- 23949949
TI  - Clinical management of resistant hypertension: practical recommendations from the
      Italian Society of Hypertension (SIIA).
AB  - According to recent hypertension guidelines, resistant hypertension is a clinical
      condition characterized by the presence of BP values above the recommended limits
      of the reference values (BP >140/90 mmHg). The prevalence of this clinical
      condition is about 10 % of the essential hypertensives. A proper diagnosis and
      management of resistant hypertension should go trough careful, mandatory clinical
      step, aimed at excluding the presence of pseudo-resistance hypertension. In this
      report, we summarized the practical recommendations are targeting both the
      general practitioner and the specialist who play an active role in the clinical
      management of patients with arterial hypertension. 

PMID- 23949950
TI  - Uneven distribution of Halobacillus trueperi species in arid natural saline
      systems of Southern Tunisian Sahara.
AB  - The genetic diversity of a collection of 336 spore-forming isolates recovered
      from five salt-saturated brines and soils (Chott and Sebkhas) mainly located in
      the hyper-arid regions of the southern Tunisian Sahara has been assessed.
      Requirements and abilities for growth at a wide range of salinities? showed that
      44.3 % of the isolates were extremely halotolerant, 23 % were moderate
      halotolerant, and 32.7 % were strict halophiles, indicating that they are adapted
      to thrive in these saline ecosystems. A wide genetic diversity was documented
      based on 16S-23S rRNA internal transcribed spacer fingerprinting profiles (ITS)
      and 16S rRNA gene sequences that clustered the strains into seven genera:
      Bacillus, Gracilibacillus, Halobacillus, Oceanobacillus, Paenibacillus,
      Pontibacillus, and Virgibacillus. Halobacillus trueperi was the most encountered
      species in all the sites and presented a large intraspecific diversity with a
      multiplicity of ITS types. The most frequent ITS type included 42 isolates that
      were chosen for assessing of the intraspecific diversity by BOX-PCR
      fingerprinting. A high intraspecific microdiversity was documented by 14 BOX-PCR
      genotypes whose distribution correlated with the strain geographic origin.
      Interestingly, H. trueperi isolates presented an uneven geographic distribution
      among sites with the highest frequency of isolation from the coastal sites,
      suggesting a marine rather than terrestrial origin of the strains. The high
      frequency and diversity of H. trueperi suggest that it is a major ecosystem
      adapted microbial component of the Tunisian Sahara harsh saline systems of marine
      origin. 

PMID- 23949951
TI  - The translocation t(2;11)(p21;q23) without MLL gene rearrangement--a possible
      marker of good prognosis in myelodysplastic syndrome patients.
AB  - The translocation t(2;11)(p21;q23) is associated with de novo myelodysplastic
      syndromes (MDS) and has an overall frequency of approximately 1%. The outcome of
      MDS patients with this translocation is not clear until now, because most of the
      clinical data addressing the t(2;11)(p21;q23) has been collected without
      investigating the status of the mixed lineage leukemia (MLL) gene. In this
      report, we present seven new patients with MDS diagnosis and the t(2;11)(p21;q23)
      in bone marrow cells; all of them without MLL gene rearrangement. They were found
      in two databases consisting of 1185 patients of two Czech institutions. These
      patients tended to be younger and showed a strong male predominance. A
      cytological and histological assessment of bone marrow at diagnosis revealed only
      mild MDS with marked dysplasia in megakaryopoiesis. Similar to other primary
      abnormalities in MDS (e.g. deletion of 11q), the t(2;11)(p21;q23) was frequently
      associated with deletion of 5q. Our results stress the common clinicopathological
      features of this entity and indicate that the t(2;11)(p21;q23) may be associated
      with a good prognosis for MDS patients (median survival 72 months).

PMID- 23949952
TI  - A miniaturized multipurpose platform for rapid, label-free, and simultaneous
      separation, patterning, and in vitro culture of primary and rare cells.
AB  - Given that current cell isolation techniques are expensive, time consuming, yield
      low isolation purities, and/or alter target cell properties, a versatile, cost
      effective, and easy-to-operate microchip with the capability to simultaneously
      separate, capture, pattern, and culture rare and primary cells in vitro is
      developed. The platform is based on target cell adhesion onto the micro
      fabricated interfaces produced by microcontact printing of cell-specific
      antibodies. Results show over 95% separation efficiency in less than 10 min for
      the separation of oligodendrocyte progenitor cells (OPCs) and cardiomyocytes from
      rat brain and heart mixtures, respectively. Target cell attachment and single
      cell spreading can be precisely controlled on the basis of the designed patterns.
      Both cell types can maintain their biofunctionality. Indeed, isolated OPCs can
      proliferate and differentiate into mature oligodendrocytes, while isolated
      cardiomyocytes retain their contractile properties on the separation platform.
      Successful separation of two dissimilar cell types present in varying
      concentrations in their respective cell mixtures and the demonstration of their
      integrity after separation open new avenues for time and cost-effective sorting
      of various cell types using the developed miniaturized platform. 

PMID- 23949953
TI  - Achondroplasia with multiple-suture craniosynostosis: a report of a new case of
      this rare association.
AB  - We report on a female patient with an exceedingly rare combination of
      achondroplasia and multiple-suture craniosynostosis. Besides the specific
      features of achondroplasia, synostosis of the metopic, coronal, lambdoid, and
      squamosal sutures was found. Series of neurosurgical interventions were carried
      out, principally for acrocephaly and posterior plagiocephaly. The most common
      achondroplasia mutation, a p.Gly380Arg in the fibroblast growth factor receptor 3
      (FGFR3) gene, was detected. Cytogenetic and array CGH analyses, as well as
      molecular genetic testing of FGFR1, 2, 3 and TWIST1 genes failed to identify any
      additional genetic alteration. It is suggested that this unusual phenotype is a
      result of variable expressivity of the common achondroplasia mutation.

PMID- 23949954
TI  - Burnout and work engagement of academics in higher education institutions:
      effects of dispositional optimism.
AB  - The aim of this study was to investigate the relationships among dispositional
      optimism, job demands and resources, burnout, work engagement, ill health and
      organizational commitment of South African academic staff in higher education
      institutions. A cross-sectional survey design was used, with stratified random
      samples (N = 595) taken of academics in South African higher education
      institutions. The results confirmed that job demands and a lack of job resources
      contributed to burnout, whereas job resources contributed to work engagement.
      Dispositional optimism had a strong direct effect on perceptions of job resources
      as well as strong indirect effects (via job resources) on burnout, work
      engagement, ill health and organizational commitment. The results of this study
      extend the dual-process model of burnout and engagement by demonstrating the
      strong effects of dispositional optimism on the constructs in the model.

PMID- 23949955
TI  - Direct measurement of the system latency of gaze-contingent displays.
AB  - Gaze-contingent displays combine a display device with an eyetracking system to
      rapidly update an image on the basis of the measured eye position. All such
      systems have a delay, the system latency, between a change in gaze location and
      the related change in the display. The system latency is the result of the delays
      contributed by the eyetracker, the display computer, and the display, and it is
      affected by the properties of each component, which may include variability. We
      present a direct, simple, and low-cost method to measure the system latency. The
      technique uses a device to briefly blind the eyetracker system (e.g., for video
      based eyetrackers, a device with infrared light-emitting diodes (LED)), creating
      an eyetracker event that triggers a change to the display monitor. The time
      between these two events, as captured by a relatively low-cost consumer camera
      with high-speed video capability (1,000 Hz), is an accurate measurement of the
      system latency. With multiple measurements, the distribution of system latencies
      can be characterized. The same approach can be used to synchronize the eye
      position time series and a video recording of the visual stimuli that would be
      displayed in a particular gaze-contingent experiment. We present system latency
      assessments for several popular types of displays and discuss what values are
      acceptable for different applications, as well as how system latencies might be
      improved. 

PMID- 23949956
TI  - 3,4-methylenedioxymethamphetamine induces gene expression changes in rats related
      to serotonergic and dopaminergic systems, but not to neurotoxicity.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is an amphetamine derivative
      widely abused by young adults. Although many studies have reported that
      relatively high doses of MDMA deplete serotonin (5-HT) content and decrease the
      availability of serotonin transporters (5-HTT), limited evidence is available as
      to the adaptive mechanisms taking place in gene expression levels in the brain
      following a dosing regimen of MDMA comparable to human consumption. In order to
      further clarify this issue, we used quantitative PCR to study the long-term
      changes induced by acute administration of MDMA (5 mg/kg * 3) in the expression
      of genes related to serotonergic and dopaminergic systems, as well as those
      related to cellular toxicity in the cortex, hippocampus, striatum, and brain stem
      of rats. Seven days after MDMA administration, we found a significantly lower
      expression of the 5-HTT (Slc6a4) and the vesicular monoamine transporter
      (Slc18a2) genes in the brain stem area. In the hippocampus, monoamine oxidase B
      (Maob) and tryptophan hydroxylase 2 (Tph2) gene expressions were increased. In
      the striatum, tyrosine hydroxylase (Th) expression was decreased, and a lower
      expression of alpha-synuclein (Snca) was observed in the cortex. In contrast, no
      significant changes were observed in the genes considered to be biomarkers of
      toxicity including the glial fibrillary acidic protein (Gfap) and the heat-shock
      70 kD protein 1A (Hspa1a) in any of the structures assayed. These results suggest
      that MDMA promotes adaptive changes in genes related to serotonergic and
      dopaminergic functionality, but not in genes related to neurotoxicity. 

PMID- 23949958
TI  - Burden of community-acquired pneumonia in Italian general practice.

PMID- 23949957
TI  - Interaction of formin FH2 with skeletal muscle actin. EPR and DSC studies.
AB  - Formins are highly conserved proteins that are essential in the formation and
      regulation of the actin cytoskeleton. The formin homology 2 (FH2) domain is
      responsible for actin binding and acts as an important nucleating factor in
      eukaryotic cells. In this work EPR and DSC were used to investigate the
      properties of the mDia1-FH2 formin fragment and its interaction with actin. MDia1
      FH2 was labeled with a maleimide spin probe (MSL). EPR results suggested that the
      MSL was attached to a single SH group in the FH2. In DSC and temperature
      dependent EPR experiments we observed that mDia1-FH2 has a flexible structure and
      observed a major temperature-induced conformational change at 41  degrees C. The
      results also confirmed the previous observation obtained by fluorescence methods
      that formin binding can destabilize the structure of actin filaments. In the EPR
      experiments the intermolecular connection between the monomers of formin dimers
      proved to be flexible. Considering the complex molecular mechanisms underlying
      the cellular roles of formins this internal flexibility of the dimers is probably
      important for manifestation of their biological functions. 

PMID- 23949959
TI  - Severely reduced diffusion capacity in idiopathic pulmonary arterial
      hypertension: patient characteristics and treatment responses.
AB  - A subgroup of patients with idiopathic pulmonary arterial hypertension (IPAH) has
      severely reduced diffusing capacity of the lung for carbon monoxide (DLCO) and
      poor prognosis. Their characteristics are currently unknown. The aim of this
      study is to contrast clinical characteristics and treatment responses of IPAH
      patients with a severely reduced and more preserved DLCO. Retrospectively, 166
      IPAH patients were included and grouped based on a DLCO cut-off value of 45% pred
      (IPAH(<45%) and IPAH(>=45%)). Clinical characteristics, treatment responses and
      survival were compared. IPAH(<45%) were older, more often male, had a more
      frequent history of coronary disease and a higher tobacco exposure. Forced
      expiratory volume in 1 s (FEV1), FEV1/forced vital capacity, total lung capacity
      and alveolar volume values were slightly lower and computed tomography scan
      abnormalities more prevalent in patients with a low DLCO. Age and number of pack
      years were independently associated with DLCO < 45% pred. IPAH(<45%) showed no
      different haemodynamic profile, yet worse exercise performance and a worse
      survival rate, which were both related to age, sex and the presence of coronary
      disease. To conclude, a severely reduced DLCO in IPAH is associated with advanced
      age and a greater tobacco exposure. These patients have a worse exercise
      performance despite a similar hemodynamic profile. We confirm the decreased
      survival in this patient group and now show that this poor outcome is related to
      age, sex and the presence of coronary disease.

PMID- 23949960
TI  - Costs of tuberculosis disease in the European Union: a systematic analysis and
      cost calculation.
AB  - Without better vaccines it is unlikely that tuberculosis (TB) will ever be
      eliminated. An investment of ~ ?560 million is considered necessary to develop a
      new, effective vaccine in the European Union (EU). However, less is known about
      the costs of TB disease in the EU. We performed a systematic review of literature
      and institutional websites addressing the 27 EU members to summarise cost data.
      We searched MEDLINE, EMBASE and Cochrane bibliographies for relevant articles.
      Combining direct and indirect costs, we arrived at an average per-TB case costs
      in the original EU-15 states plus Cyprus, Malta and Slovenia of ?10 282 for drug
      susceptible TB, ?57 213 for multidrug resistant (MDR)-TB and ?170 744 for
      extensively drug resistant (XDR)-TB. In the remaining new EU states, costs
      amounted to ?3427 for drug-susceptible TB and ?24 166 for MDR-TB/XDR-TB. For the
      70 340 susceptible TB cases, 1488 MDR-TB and 136 XDR-TB cases notified in 2011
      costs of ?536 890 315 accumulated in 2012. In the same year, the 103 104
      disability-adjusted life years caused by these cases, when stated in monetary
      terms, amounted to a total of ?5 361 408 000. Thus, the resulting economic burden
      of TB in the EU clearly outweighs the cost of investing in more efficient
      vaccines against TB.

PMID- 23949961
TI  - Sex and haemodynamics in pulmonary arterial hypertension.
AB  - Female sex is a risk factor for pulmonary arterial hypertension (PAH), yet
      females have better survival than males. We sought to determine if sex was
      associated with baseline haemodynamics in subjects with PAH, and whether age
      modified these relationships. We conducted a pooled analysis from 11 randomised
      trials submitted to the US Food and Drug Administration. The study sample
      included 1211 subjects with idiopathic PAH, 25% of whom were males, and 489
      subjects with connective tissue disease-associated PAH, 13% of whom were males.
      After multivariable adjustment, right atrial pressure was 1.36 mmHg higher (95%
      CI 0.44-2.27, p=0.004), cardiac index was -0.14 L . min(-1) . m(-2) lower (95% CI
      -0.23-0.04, p=0.01) and pulmonary vascular resistance was 1.23 Wood units higher
      (95% CI 0.18-2.27, p=0.02) in males compared with females. Younger males had 5.43
      mmHg (95% CI 2.20-8.66, p=0.001) higher mean pulmonary arterial pressures than
      younger females, but these relationships were attenuated after age 45 years. In
      the subgroup of connective tissue disease-associated PAH, males may have had
      higher right atrial pressure. These findings implicate age as a modifier and
      provide further evidence of sexual dimorphism in PAH.

PMID- 23949962
TI  - Domiciliary diurnal variation of exhaled nitric oxide fraction for asthma
      control.
AB  - A major goal of asthma management is maintaining optimal control. Current
      assessment is based on symptoms and lung function. We evaluated whether
      domiciliary daily home exhaled nitric oxide fraction (FeNO) monitoring could be
      useful as an index of asthma control. 50 asthmatic subjects and 15 healthy
      volunteers with a range of asthma severity underwent asthma control questionnaire
      (ACQ), spirometry before and after salbutamol and sputum induction. FeNO and peak
      expiratory flow (PEF) were measured twice daily for 2 weeks. A record of
      exacerbations was obtained 3 months later. Diurnal FeNO variation in uncontrolled
      asthmatics was significantly greater than in controlled asthmatics (p<0.01). PEF
      variation was not different. The daily variation of FeNO levels was also greater
      in uncontrolled asthmatics compared with controlled asthmatic and healthy
      subjects (p<0.01). 80% of uncontrolled asthmatics experienced at least one or
      more exacerbations over the 3 months after the enrolment. The combination of
      diurnal FeNO variation >= 16.6% and ACQ scores >= 1.8 was best at predicting
      uncontrolled asthma (area under curve 0.91, 95% CI 0.86-0.97; p<0.001). Diurnal
      variation in FeNO can be used as a biomarker of asthma control and as a predictor
      of the risk of future exacerbation. Prospective studies are warranted.

PMID- 23949963
TI  - Umeclidinium in patients with COPD: a randomised, placebo-controlled study.
AB  - Efficacy and safety of umeclidinium administered in a dry power inhaler were
      evaluated in moderate-to-very-severe chronic obstructive pulmonary disease
      patients. This was a randomised, placebo-controlled study assessing once-daily
      umeclidinium 62.5 and 125 MUg over 12 weeks. The primary end-point was change
      from baseline in trough forced expiratory volume in 1 s (FEV1) on day 85.
      Secondary end-points were 0-6-h weighted mean and serial forced expiratory volume
      in 1 s. Other end-points were transitional dyspnoea index, health outcomes (St
      George's Respiratory Questionnaire), pharmacokinetics and safety. 246 patients
      were enrolled; 168 completed the study. On day 85, umeclidinium 62.5 and 125 MUg
      significantly improved least squares mean change from baseline in trough FEV1
      (127 and 152 mL, respectively; p<0.001) compared with placebo. On day 84,
      umeclidinium 62.5 and 125 MUg significantly improved least squares mean change
      from baseline in 0-6-h weighted mean (166 and 191 mL, respectively; p<0.001) and
      serial FEV1 at each time point (p<=0.003). Significant improvements in least
      squares mean transitional dyspnoea index focal score for UMEC 125 mg(1.3 units;
      p,0.05) and change from baseline St George's Respiratory Questionnaire total
      score for both UMEC doses (-7.9 and -10.87 units, for UMEC 62.5 mg and 125 mg,
      respectively; both p,0.001) were noted compared with placebo at week 12 [DOSAGE
      ERROR CORRECTED].The incidence of adverse events was low and similar across
      treatments. Umeclidinium 62.5 and 125 MUg significantly improved lung function,
      dyspnoea and health status compared with placebo, and were well tolerated in
      chronic obstructive pulmonary disease patients over 12 weeks.

PMID- 23949964
TI  - Occupational exposures and uncontrolled adult-onset asthma in the European
      Community Respiratory Health Survey II.
AB  - Occupational exposure is a well-recognised modifiable risk factor for asthma, but
      the relationship between occupational exposure and asthma control has not been
      studied. We aimed to study this association among working-age adults from the
      European Community Respiratory Health Survey (ECRHS). Data were available for
      7077 participants (mean age 43 years, 45% never-smokers, 5867 without asthma and
      1210 with current asthma). Associations between occupational exposure to specific
      asthmagens and asthma control status (33% with uncontrolled asthma, based on the
      Global Initiative for Asthma guidelines) were evaluated using logistic and
      multinomial regressions, adjusted for age, sex and smoking status, with study
      areas included as a random effect. Statistically significant positive
      associations were observed between uncontrolled adult-onset asthma and both past
      12-month and 10-year exposure to any occupational asthmagens (OR (95% CI) 1.6
      (1.0-2.40) and 1.7 (1.2-2.5), respectively); high (1.7 (1.0-2.8) and 1.9 (1.3
      2.9), respectively) and low (1.6 (1.0-2.7) and 1.8 (1.2-2.7), respectively)
      molecular weight agents; and cleaning agents (2.0 (1.1-3.6) and 2.3 (1.4-3.6),
      respectively), with stronger associations for long-term exposures. These
      associations were mainly explained by the exacerbation domain of asthma control
      and no associations were observed between asthmagens and partly controlled
      asthma. These findings suggest that occupational exposure to asthmagens is
      associated with uncontrolled adult-onset asthma. Occupational risk factors should
      be quickly identified to prevent uncontrolled asthma. 

PMID- 23949965
TI  - Phenotype profiling of primary testicular diffuse large B-cell lymphomas.
AB  - Primary testicular diffuse large B-cell lymphomas (tDLBCL) are rare neoplasms
      with few comprehensive studies conducted so far. We aimed to systematically
      characterize the phenotype of tDLBCL. Forty-five patients from three Swiss
      hospitals diagnosed with tDLBCL between 1972 and 2009 were reviewed and included
      in this study. A tissue microarray was assembled, and the protein expression
      profiles were assessed by immunohistochemistry and fluorescence in situ
      hybridization for the C-MYC locus. All tDLBCL expressed CD79a, followed by CD20
      (98% of cases) and CD19 (93%). One case expressed the germ cell marker OCT4 and
      showed a rearrangement of C-MYC. Eighty-two per cent of cases showed active STAT
      signalling by expression of either pSTAT1 or pSTAT3 or both, but not pSTAT5. The
      p53 was overexpressed in 10% of cases, but p21 staining (?p21/p53) did not
      suggest the presence of TP53 mutations. tDLBCL had a median MIB1 labelling index
      of 40%, and only 6% of cases appeared to have C-MYC rearrangements. Most cases
      were of the non-germinal centre type (77%), and showed as expected for this cell
      of origin B-cell lymphoma 2 (BCL2) rearrangements only in 4% and amplifications
      in 15% of cases, whereas BCL6 was rearranged in 48% of cases. CXCR4 was expressed
      in 52% of cases, and high CXCR4 expression was of prognostic significance for
      progression-free survival (p = 0.003). Because 84% of cases expressed nuclear
      p50, the canonical NF-kappaB signalling pathway seems to be active. Multimarker
      phenotyping is important for lineage determination of tDLBCL. Occasionally,
      tDLBCL can express germ cell markers like OCT4, and they have active STAT
      signalling mediated through pSTAT1 and pSTAT3 and active canonical NF-kappaB
      signalling. tDLBCL are of non-germinal centre/post-germinal centre cell origin
      and not hyperproliferative. TP53 mutations are unlikely, and C-MYC as well as
      BCL2 rearrangements are rare, whereas BCL6 is commonly rearranged. CXCR4 might
      prove to be the first protein-based prognostic marker for tDLBCL, inciting
      studies in larger cohorts corroborating these findings.

PMID- 23949967
TI  - Silicon quantum dots for biological applications.
AB  - Semiconductor nanoparticles (or quantum dots, QDs) exhibit unique optical and
      electronic properties such as size-controlled fluorescence, high quantum yields,
      and stability against photobleaching. These properties allow QDs to be used as
      optical labels for multiplexed imaging and in drug delivery detection systems.
      Luminescent silicon QDs and surface-modified silicon QDs have also been developed
      as potential minimally toxic fluorescent probes for bioapplications. Silicon, a
      well-known power electronic semiconductor material, is considered an extremely
      biocompatible material, in particular with respect to blood. This review article
      summarizes existing knowledge related to and recent research progress made in the
      methods for synthesizing silicon QDs, as well as their optical properties and
      surface-modification processes. In addition, drug delivery systems and in vitro
      and in vivo imaging applications that use silicon QDs are also discussed.

PMID- 23949966
TI  - Search for genetic modifiers of IRF6 and genotype-phenotype correlations in Van
      der Woude and popliteal pterygium syndromes.
AB  - Van der Woude syndrome is the most common form of syndromic orofacial clefting,
      accounting for 1-2% of all patients with cleft lip and/or cleft palate. Van der
      Woude and popliteal pterygium syndromes are caused by mutations in IRF6, but
      phenotypic variability within and among families with either syndrome suggests
      that other genetic factors contribute to the phenotypes. The aim of this study
      was to identify common variants acting as genetic modifiers of IRF6 as well as
      genotype-phenotype correlations based on mutation type and location. We
      identified an association between mutations in the DNA-binding domain of IRF6 and
      limb defects (including pterygia). Although we did not detect formally
      significant associations with the genes tested, borderline associations suggest
      several genes that could modify the VWS phenotype, including FOXE1, TGFB3, and
      TFAP2A. Some of these genes are hypothesized to be part of the IRF6 gene
      regulatory network and may suggest additional genes for future study when larger
      sample sizes are also available. We also show that families with the Van de Woude
      phenotype but in whom no mutations have been identified have a lower frequency of
      cleft lip, suggesting there may be locus and/or mutation class differences in Van
      de Woude syndrome.

PMID- 23949968
TI  - Macrophage involvement in mitral valve pathology in mucopolysaccharidosis type VI
      (Maroteaux-Lamy syndrome).
AB  - Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI) is a rare lysosomal
      storage disorder in which the pathologic storage of glycosaminoglycans in various
      tissues can lead to severe symptoms, including cardiomyopathy. We report on a
      child with Maroteaux-Lamy syndrome whose cardiac condition deteriorated and
      eventually led to cardiac failure at the age of 7 years due to severe mitral
      regurgitation. She received a mitral valve replacement and tricuspid repair with
      successful outcome. Histologic examination of the mitral valve showed abundant
      "clear" cells in both the leaflets and chordae tendineae. In Hurler disease (MPS
      I), similar cells have been identified as activated valvular interstitial cells
      (VICs, a myofibroblast like cell type). Here we report that the "clear" cells are
      CD68 positive, a frequently used marker of macrophage lineage. The "clear" cells
      remained unstained with the more specific macrophage marker CD14 while persistent
      staining of other cells demonstrated macrophage infiltration. From these
      observations, we infer that macrophages are involved in mitral valve pathology in
      MPS VI.

PMID- 23949969
TI  - Effects of self-reported osteoarthritis on physical performance: a longitudinal
      study with a 10-year follow-up.
AB  - BACKGROUND AND AIMS: Osteoarthritis (OA) of the knee or hip is associated with
      limitations in activities of daily life. There are only a few long-term studies
      on how knee or hip OA affects the course of physical performance. The aim of this
      study was to investigate the effects of knee or hip OA on physical performance
      during a follow-up period of 10 years. METHODS: Participants in the Longitudinal
      Aging Study Amsterdam with self-reported hip or knee OA (N = 155) were
      prospectively followed for 10 years on 4 occasions from the onset of OA and
      compared to participants without OA (N = 1004). Physical performance was tested
      with walk, chair stand and balance tests. Scores for each test were summed to a
      total performance score (range 0-12), higher scores indicating better
      performance. Generalized estimating equations were used to analyze differences
      between participants with and without OA, unadjusted as well as adjusted for
      confounders. RESULTS: There was a significant interaction between OA and sex (P =
      0.068). Both in men and women, total performance was lower for participants with
      OA, with greater differences in men. Chair stand and walking performance (P <
      0.05), but not balance, were lower in participants with OA. After adjustment for
      confounders, these associations remained significant in men but not in women.
      Additional analyses correcting for follow-up duration and attrition showed lower
      performance scores for men and women with OA. CONCLUSIONS: OA negatively affected
      physical performance 3-6 years after it was first reported. Performance in men
      with OA was more affected than in women.

PMID- 23949970
TI  - Pattern of use and presenting complaints of older patients visiting an Emergency
      Department in Italy.
AB  - BACKGROUND AND AIMS: The number of older persons admitted to the Emergency
      Department (ED) is dramatically increasing due to their complex medical and
      social problems, which in turn lead to longer clinical evaluation times and
      increased use of resources compared to younger adults. However, scant data are
      available for Italian EDs. Similarly, no data are available about the reasons to
      ED visit and its role in determining the ED utilization pattern. The study aimed
      at describing the pattern of ED use by older patients and main presenting
      complaints. METHODS: Cross-sectional descriptive study of 5,826 ED patients in
      the city of Fano (Italy). Identifiers and triage, clinical and social data were
      collected. Presenting complaints as recorded by triage nurses have been recoded
      according to the Canadian Emergency Department Information System list version
      1.1. Data were analyzed comparing older patients (more than 65 years-old) with
      younger adults (less than 65 years-old). RESULTS: The prevalence of ED visits by
      older adults was 23.9 %. Their visits were characterized by higher emergency
      levels, admission rate and length of ED stay. Trauma was the main reason for ED
      presentation, especially among young adults, but elderly trauma patients were
      more frequently admitted because of hip fracture. Dyspnea and abdominal pain were
      the most frequent non-trauma presenting complaints among geriatric patients and
      represented the main causes for admission. CONCLUSIONS: Older adults use the ED
      appropriately also in Italy. Trauma with complications (fracture) and various
      presenting complaints underlying medical problems accounted for more than 50 % of
      ED visits and hospital admissions.

PMID- 23949971
TI  - Molecular aspects of the cardioprotective effect of exercise in the elderly.
AB  - Aging is a well-recognized risk factor for several different forms of
      cardiovascular disease. However, mechanisms by which aging exerts its negative
      effect on outcome have been only partially clarified. Numerous evidence indicate
      that aging is associated with alterations of several mechanisms whose integrity
      confers protective action on the heart and vasculature. The present review aims
      to focus on the beneficial effects of exercise, which plays a pivotal role in
      primary and secondary prevention of cardiovascular diseases, in counteracting age
      related deterioration of protective mechanisms that are crucially involved in the
      homeostasis of cardiovascular system. In this regard, animal and human studies
      indicate that exercise training is able: (1) to improve the inotropic reserve of
      the aging heart through restoration of cardiac beta-adrenergic receptor
      signaling; (2) to rescue the mechanism of cardiac preconditioning and
      angiogenesis whose integrity has been shown to confer cardioprotection against
      ischemia and to improve post-myocardial infarction left ventricular remodeling;
      (3) to counteract age-related reduction of antioxidant systems that is associated
      to decreased cellular resistance to reactive oxygen species accumulation.
      Moreover, this review also describes the molecular effects induced by different
      exercise training protocols (endurance vs. resistance) in the attempt to better
      explain what kind of exercise strategy could be more efficacious to improve
      cardiovascular performance in the elderly population. 

PMID- 23949972
TI  - Brain activation during dual-task walking and executive function among older
      adults with mild cognitive impairment: a fNIRS study.
AB  - BACKGROUND AND AIMS: Dual-task walking (DTW) is thought to involve activation of
      the prefrontal cortex in healthy adults and to be affected by cognitive
      impairment. However, it is unclear whether prefrontal cortex activation is
      involved in DTW in older adults with mild cognitive impairment. This study
      examined brain activation during DTW among older adults with mild cognitive
      impairment using functional near-infrared spectroscopy. METHODS: Sixteen older
      adults (aged 75.4 +/- 7.2 years, women n = 6) performed gait experiments under
      normal walking and DTW conditions. We used a design with 60-s blocks consisting
      of a 10-s rest standing as pre-resting period, a 20-s walking task period, and a
      30-s rest standing as post-resting period. Walking speed was measured during a 20
      s walking task. Changes in oxy-hemoglobin were measured in the prefrontal area
      during gait experiments. RESULTS: Walking speed was slower during DTW compared
      with normal walking (p < 0.001). The oxy-hemoglobin level during DTW was higher
      than during normal walking (p < 0.001) and was correlated with executive
      function, as measured by Stroop interference (p < 0.05). CONCLUSION: Our findings
      indicate that DTW is associated with prefrontal activation among older adults
      with mild cognitive impairment. The brain activation during DTW was correlated
      with executive function. Additional studies are necessary to elucidate the
      effects of cognitive impairment on the association between prefrontal activity
      and walking under various conditions.

PMID- 23949973
TI  - Life-Space Assessment scale to assess mobility: validation in Latin American
      older women and men.
AB  - BACKGROUND: The Life-Space Assessment (LSA) instrument of the University of
      Alabama and Birmingham study is a useful and innovative measure of mobility in
      older populations. The purpose of this article was to assess the reliability,
      construct and convergent validity of the LSA in Latin American older populations.
      METHODS: In a cross-sectional study, a total of 150 women and 150 men, aged 65-74
      years, were recruited from seniors' community centers in Manizales, Colombia and
      Natal, Brazil. The LSA questionnaire summarizes where people travel (5 levels
      from room to places outside of town), how often and any assistance needed. Four
      LSA variables were obtained according to the maximum life space achieved and the
      level of independence. As correlates of LSA, education, perception of income
      sufficiency, depression, cognitive function, and functional measures (objective
      and subjectively measured) were explored. The possible modifying effect of the
      city on correlates of LSA was examined. RESULTS: Reliability for the composite
      LSA score was substantial (ICC = 0.70; 95 % CI 0.49-0.83) in Manizales. Average
      levels of LSA scores were higher in those with better functional performance and
      those who reported less mobility difficulties. Low levels of education,
      insufficient income, depressive symptoms, and low scores of cognitive function
      were all significantly related to lower LSA scores. Women in both cities were
      more likely to be restricted to their neighborhood and had lower LSA scores.
      CONCLUSION: This study provides evidence for the validity of LSA in two Latin
      American populations. Our results suggest that LSA is a good measure of mobility
      that reflects the interplay of physical functioning with gender and the social
      and physical environment.

PMID- 23949974
TI  - Is inferior vena caval filter an alternative treatment option for geriatric
      patients that cannot use anticoagulation therapy?
AB  - The incidence of deep vein thrombosis (DVT) and pulmonary embolism has been
      increasing in the elderly because of hypercoagulability associated with aging.
      Age has also been identified as an independent risk factor for bleeding
      complications related to anticoagulation therapy. Inferior vena cava filters
      could be used as alternatives to anticoagulant therapy for the prevention of
      pulmonary embolism when anticoagulation is either contraindicated or ineffective.
      Here, we report two geriatric patients who had documented acute DVT and in whom
      inferior vena caval filter was used because of the patients have a
      contraindication to use an anticoagulation. 

PMID- 23949975
TI  - Effects of preventive home visits on health care costs for ambulatory frail
      elders: a randomized controlled trial.
AB  - BACKGROUND AND AIMS: Reducing health care costs through preventive geriatric care
      has become a high priority in Japan. We analyzed data from a randomized
      controlled trial to examine the effects of a preventive home visit program on
      health care costs among ambulatory frail elders. METHODS: Structured preventive
      home visits by nurses or care managers were provided to the visit group every 6
      months over 2 years. The enrolled participants (N = 323) were randomly assigned
      to either the visit group (N = 161) or the control group (N = 162). We analyzed
      the health care costs, including the costs for hospitalizations and outpatient
      clinic utilization for participants who had health care insurance from the local
      government (N = 307). The visit group included 154 individuals in the visit group
      and 153 people in the control group. RESULTS: Total health care costs over the
      study period were not significantly different between groups, but at most monthly
      time points costs and those for outpatient clinic utilization in the visit group
      were lower than those in the control group. Hospitalizations, which accounted for
      more than Y 500,000 JPY per month, were less likely to occur more often among
      participants in the visit group (N = 71) than in the control group (N = 113) (OR
      = 0.63; p = 0.002). CONCLUSIONS: These results suggest that a preventive home
      visit program may reduce monthly health care costs, primarily by reducing
      hospitalization costs.

PMID- 23949976
TI  - An association between polymorphism of the NADH/NADPH oxidase p22phox (phagocyte
      oxidase) subunit and aging in Turkish population.
AB  - BACKGROUND AND AIMS: Aging is a complex and multifactorial process that is
      stimulated by a number of factors including genes and life-style. It is thought
      that the production of reactive oxygen species (ROS) in the face of antioxidant
      enzymes and molecules is related to aging and age-related diseases. NAD(P)H
      oxidase system is the predominant cellular source of ROS, and p22phox, the major
      component of that system, is essential for the activation of NAD(P)H oxidase. The
      aim of this study was to investigate the association between p22phox C242T single
      nucleotide polymorphism and aging in Turkish population. METHODS: Blood samples
      were collected from 332 volunteers between 18 and 95 years of age and were
      classified into three groups according to their ages as <65, 65-84 and >= 85.
      p22phox C242T polymorphism was genotyped by PCR-RFLP method. RESULTS: CC genotype
      frequency in the C242T polymorphism is higher in older group (>= 85) than younger
      groups (<65 and 65-85), whereas CT + TT genotype frequency is lower in older
      group. When the p22phox C242T polymorphism was compared with the mean ages and
      age groups, statistically significant associations were found. CONCLUSIONS: We
      showed for the first time that human aging is significantly associated with
      p22phox C242T genotypes in Turkish population, being highest in CC, intermediate
      in CT, and lowest in TT homozygote. It is plausible to suggest that CC genotype
      might protect people from chronic inflammation, diseases as well as from
      oxidative stress and, thus, individuals with CC genotype might be more
      advantageous for aging as compared to those with CT + TT genotypes.

PMID- 23949977
TI  - Marginal donors: can older donor hearts tolerate prolonged cold ischemic storage?
AB  - BACKGROUND AND AIMS: Both advanced donor age and prolonged ischemic time are
      significant risk factors for the 1-year mortality. However, its functional
      consequences have not been fully evaluated in the early-phase after
      transplantation; even early graft dysfunction is the main determinant of long
      term outcome following transplantation. We evaluated in vivo left-ventricular
      (LV) cardiac and coronary vascular function of old-donor grafts after short and
      prolonged cold ischemic times in rats 1 h after heart transplantation. METHODS:
      The hearts were excised from young donor (3-month-old) or old donor (18-month
      old) rats, stored in cold preservation solution for either 1 or 8 h, and
      heterotopically transplanted. RESULTS: After 1 h of ischemic period, in the old
      donor group, LV pressure, maximum pressure development (dP/dt max), time constant
      of LV pressure decay (tau), LV end-diastolic pressure and coronary blood flow did
      not differ compared with young donors. However, endothelium-dependent
      vasodilatation to acetylcholine resulted in a significantly lower response of
      coronary blood flow in the old-donor group (33 +/- 4 vs. 51 +/- 15 %, p < 0.05).
      After 8 h preservation, two of the old-donor hearts showed no mechanical activity
      upon reperfusion. LV pressure (55 +/- 6 vs. 72 +/- 5 mmHg, p < 0.05), dP/dt max
      (899 +/- 221 vs. 1530 +/- 217 mmHg/s, p < 0.05), coronary blood flow and response
      to acetylcholine were significantly reduced and tau was increased in the old
      donor group in comparison to young controls. CONCLUSIONS: During the early-phase
      after transplantation, the ischemic tolerance of older-donor hearts is reduced
      after prolonged preservation time and the endothelium is more vulnerable to
      ischemia/reperfusion.

PMID- 23949978
TI  - Optimization of a Trap for Tuta absoluta Meyrick (Lepidoptera: Gelechiidae) and
      Trials to Determine the Effectiveness of Mass Trapping.
AB  - Management of the South American tomato leafminer, Tuta absoluta Meyrick, with
      insecticides has led to the widespread development of insect resistance. Mass
      trapping using traps baited with the female-produced sex pheromone is an
      attractive alternative for the management of this pest. The current study
      evaluated several commercial trap designs for capture of T. absoluta. Based on
      its small size and ease of handling, the most effective trap is a small plastic
      container with entry windows cut on the sides filled with motor oil over water.
      These traps are most effective when placed near ground level. Tests of septa
      containing 0.1 or 0.2 mg of the pheromone (95:5) E4, Z8-14Ac/E4,Z8,Z11-14Ac were
      slightly more attractive than septa loaded with 0.5, 1.0, or 2 mg during the
      first week of use, but the latter three loadings were slightly more attractive
      than the first two loadings after 9 weeks. Ideal trap baits were loaded with 0.5
      mg of pheromone. Higher numbers of T. absoluta were captured near upwind borders
      of tomato fields suggesting that treatments against T. absoluta should be
      concentrated near upwind parts of fields. Comparisons of conventional insecticide
      treatment versus mass trapping to manage T. absoluta damage in three different
      test sites showed that even when initial captures in monitoring traps were high
      (>35 males trap(-1) day(-1)), mass trapping at 48 traps/ha reduced leaf damage
      more efficiently than conventional insecticide treatment. Based on the typical
      insecticide recommendations against T. absoluta, mass trapping is an economically
      viable alternative. 

PMID- 23949979
TI  - Description of the Pupa of Culicoides crucifer Clastrier (Diptera:
      Ceratopogonidae).
AB  - The pupa of Culicoides crucifer Clastrier is described, illustrated and
      photomicrographed by using binocular microscope and phase-contrast microscopy
      from material collected in an artificial container in Manaus, Brazil. The pupa
      shows features typical of pupae occurring in calm and clean waters, and it is
      compared with its similar congeners of the subgenus Haematomyiidium, Culicoides
      annuliductus Wirth and Culicoides debilipalpis Lutz. 

PMID- 23949980
TI  - Richness and Abundance of Ichneumonidae in a Fragmented Tropical Rain Forest.
AB  - Because of the magnitude of land use currently occurring in tropical regions, the
      local loss of animal species due to habitat fragmentation has been widely
      studied, particularly in the case of vertebrates. Many invertebrate groups and
      the ichneumonid wasps in particular, however, have been poorly studied in this
      context, despite the fact that they are one of the most species-rich groups and
      play an important role as regulators of other insect populations. Here, we
      recorded the taxonomic composition of ichneumonid parasitoids and assessed their
      species richness, abundance, similarity, and dominance in the Los Tuxtlas
      tropical rain forest, Mexico. We compared two forest types: a continuous forest
      (640 ha) and a forest fragment (19 ha). We sampled ichneumonids using four
      malaise traps in both forest types during the dry (September-October) and rainy
      (March-April) seasons. A total of 104 individuals of Ichneumonidae belonging to
      11 subfamilies, 18 genera, and 42 species were collected in the continuous forest
      and 11 subfamilies, 15 genera, and 24 species were collected in the forest
      fragment. Species richness, abundance, and diversity of ichneumonids were greater
      in the continuous forest than in the forest fragment. We did not detect
      differences between seasons. Species rank/abundance curves showed that the
      ichneumonid community between the forest types was different. Species similarity
      between forest types was low. The most dominant species in continuous forest was
      Neotheronia sp., whereas in the forest fragment, it was Orthocentrus sp. Changes
      in the ichneumonid wasp community may compromise important tropical ecosystem
      processes. 

PMID- 23949981
TI  - Old Fragments of Forest Inside an Urban Area Are Able to Keep Orchid Bee
      (Hymenoptera: Apidae: Euglossini) Assemblages? The Case of a Brazilian Historical
      City.
AB  - Retention of habitat fragments within the urban matrix can provide critical
      resources for the maintenance of regional biodiversity while still providing
      socio-economic value. Euglossini bees are important components in a community as
      they are important pollinators for economically valuable plants as well as
      hundreds of orchid species. However, some species are very sensitive to
      environmental impacts like urbanization. This study presents the role of antique
      urban fragments in a historical city in Brazil and compares it with a
      conservation area on the aspects of orchid bee assemblage, such as richness,
      composition, and abundance. Four fragments inside the city of Ouro Preto and
      three inside Parque Estadual do Itacolomi (PEIT) were sampled for Euglossini
      bees. Sorensen similarity index was used to compare community composition. The
      Mantel test was applied to verify the hypothesis that an urban center is a
      barrier for the mobility of the individuals. Fourteen Euglossini species from the
      region were registered. Close to 75% of the sampled bees were collected from the
      PEIT sampling areas. The fragments presented differences in Euglossini richness
      and abundance. A majority of the sampled fragments were dominated by the Eulaema
      cingulata Fabricius, Eulaema nigrita Lepeletier, and Euglossa securigera Dressler
      species. We found differences on community composition between the fragments
      localized in PEIT and those located in the urban center. The data suggest that
      there is a possible flux of individuals between the sampled fragments. The
      various small forest fragments in Ouro Preto, primarily in backyards, may also
      serve as stepping stones between sampled fragments. 

PMID- 23949982
TI  - Effect of Low-Temperature Storage on Diaeretiella rapae (McIntosh) (Hymenoptera:
      Braconidae).
AB  - We evaluated the effects of constant low-temperature storage on Diaeretiella
      rapae (McIntosh) (Braconidae, Aphidiinae). Diaeretiella rapae mummies were stored
      at 5 +/- 1 degrees C for 0-36 days. The percentage of D. rapae emergence varied
      (100-83%) after 0-32 days of storage. After 32 days, emergence reduced to 55%.
      According to our Probit analysis, 50% mortality (LT50) of the population of D.
      rapae was reached after 40 days of storage at 5 degrees C. Storage for up to 32
      days did not negatively affect emergence and survival. Cold exposure of D. rapae
      for 36 days did not influence morphological malformations, sex ratio, and
      emergence of the F1 generation. After 4-36 days of storage, D. rapae showed a
      gradual decrease in emergence, longevity, reproductive capacity, and F1 sex
      ratio. Diaeretiella rapae can be stored for up to 24 days at 5 degrees C, at
      which time the percentage of parasitism and the F1 sex ratio remain above 38% and
      at 0.50, respectively. 

PMID- 23949983
TI  - Records of the Genus Paramerina (Diptera: Chironomidae: Tanypodinae) from Eastern
      Himalaya and Satpura Hill Regions of India.
AB  - The pupa and the male imago of Paramerina valida n. sp. and the larva of
      Paramerina inficia Chaudhuri & Debnath are described and illustrated along with a
      brief re-description of the adult of P. inficia from the Eastern Himalaya and
      Satpura hill regions of India. A key to the adult males of the Indian species of
      the genus Paramerina Fittkau is provided. The notes on ecology of the two species
      are also provided. 

PMID- 23949984
TI  - A New Species of the Genus Adela (Lepidoptera: Adelidae) from South America.
AB  - Adela boliviella n. sp., described from central Bolivia, is the first
      representative of the subfamily Adelinae found in South America. This species is
      closely related to Adela astrella Walsingham, from which it differs by larger
      compound eyes in males (interocular index, i.e. the ratio of vertical eye
      diameter to interocular distance, equals 1.5 compared to 0.75 in A. astrella),
      smaller extent of pale yellow scales in the forewing (0.25* forewing length
      compared to 0.40 in A. astrella), absence of a silver band outside the fascia and
      presence of three glossy silver spots near the apex of the forewing (six in A.
      astrella). 

PMID- 23949985
TI  - High Variation in Single Nucleotide Polymorphisms (SNPs) and Insertions/Deletions
      (Indels) in the Highly Invasive Bemisia tabaci (Gennadius) (Hemiptera:
      Aleyrodidae) Middle East-Asia Minor 1 (MEAM1).
AB  - Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) Middle East-Asia Minor 1
      (MEAM1) is invasive and adaptive to varied environments throughout the world. The
      adaptability is closely related to genomic variation such as single nucleotide
      polymorphisms (SNPs) and insertions/deletions (indels). In order to elucidate the
      feature of SNPs and indels in MEAM1, and reveal the association between
      SNPs/indels and adaptive capacity to various environments, a computational
      approach with QualitySNP was used to identify reliable SNPs and indels on the
      basis of 9110-expressed sequence tags of MEAM1 present in the NCBI database.
      There were 575 SNPs detected with a density of 10.1 SNPs/kb and 6.4 SNPs/contig.
      Also, 237 transitions (39.3%) and 366 transversions (60.7%) were obtained, where
      the ratio of transitions to transversions was 0.65:1. In addition, 581 indels
      with a density of 14.1 indels/kb and 9.2 indels/contig were detected.
      Collectively, it showed that invasive MEAM1 has high SNPs density, and higher
      SNPs percentage than non-invasive B. tabaci species. A high SNPs
      density/percentage in MEAM1 yielded a high genomic variation that might have
      allowed it to adapt to varied environments, which provides some support to
      understand the invasive nature of MEAM1 at the genomic level. High levels of
      genomic variation are implicated in the level of adaptive capacity and invasive
      species are thought to exhibit higher levels of adaptive capacity than non
      invasive species. 

PMID- 23949986
TI  - Production of Sexuals and Mating Frequency in the Stingless Bee Tetragonisca
      angustula (Latreille) (Hymenoptera, Apidae).
AB  - Queen, worker, and male production was studied for 1 year in three queenright
      colonies of Tetragonisca angustula (Latreille). We sampled brood combs monthly
      and noticed that the number of brood cells and production of individuals were
      similar among colonies. Although the production of queens did not vary
      significantly, the frequencies of workers, males, and the number of cells among
      the combs varied over time. The production of males was highly seasonal,
      occurring mostly from February to April, coinciding with the period of intense
      brood cells production, when colonies produced more males and less workers,
      resulting in a negative correlation. Although the frequency of queens has not
      varied in time, the seasonal availability of males affected the mating frequency
      and the time spent since emergence until fertilization of queens. In the T.
      angustula colonies studied, the population dynamics was highly seasonal and the
      mating success depended of male production, according to the season. 

PMID- 23949987
TI  - Percentage of Impervious Surface Soil as Indicator of Urbanization Impacts in
      Neotropical Aquatic Insects.
AB  - Several recent studies have shown a strong correlation between the area of
      impervious surface soil (IS) and the insect community structure from urban
      streams. This study assessed whether this relationship is observed in Neotropical
      streams. We examined if an increased IS reduces the diversity and simplifies the
      trophic structure of the community of Ephemeroptera, Plecoptera, and Trichoptera.
      An IS threshold was detected between 1.6 and 9.3%, in which there is a change in
      the community, both in taxonomic richness and trophic structure. Among the 27
      genera identified, only 15 occurred in streams with IS > 9%, while 24 genera were
      registered in streams with IS < 2%. The trophic guilds of predators and shredders
      were not observed in streams with high IS, decreasing the number of guilds in
      these streams from 5 to 3, compared with the streams with low IS. Three
      hypotheses with cumulative effect have been proposed to explain such variations.
      Based on the IS threshold verified, the creation of a mosaic of land use, where
      some subbasins would be sacrificed and others would be preserved, was suggested
      as a mitigation measure for the impacts caused by urbanization in the Neotropical
      aquatic insects' fauna. 

PMID- 23949988
TI  - A comparative observational study of early versus delayed feeding after
      percutaneous endoscopic gastrostomy.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is the procedure of choice
      for long-term enteral feeding. OBJECTIVE: This prospective observational study
      was carried out to compare the safety of commencing feeding 3 h compared to 16-24
      h after PEG tube placement. METHODS: One hundred and ten patients with
      oropharyngeal malignancies who had consented for PEG were enrolled. Trial
      specific consent and IRB approval were not obtained because at the time when this
      study was done, this was not mandatory for observational studies which involved
      standard procedures. Alternate patients were started on early feeding within 3 h
      (group I) or after overnight observation of 16 to 24 h (group II). Five hundred
      milliliters of Ringer's lactate was infused over 4 h initially, followed 2 h
      later by 200 mL of formula feed. The patients were advised to take bolus feeds of
      200 mL every 2 h and oral feeds ad libitum from the next day. All patients were
      evaluated on days 1, 2, 7, and 30. RESULTS: There were 55 patients (47 males) in
      group I and 54 patients (38 males) in group II who were matched for age (mean age
      46.1 and 46.1 years, respectively). Complications included PEG site infection
      (1), peristomal leak (3), and displacement of the PEG tube (1) in group I. PEG
      site infection was seen in five patients in group II. All the complications were
      managed conservatively on an ambulatory basis. CONCLUSION: Initiation of tube
      feeding 3 h after an uncomplicated PEG was safe, well tolerated, and helped to
      reduce the hospital stay.

PMID- 23949989
TI  - Extensive hepatic necrosis after transarterial chemoembolization.

PMID- 23949990
TI  - Inferior vena cava thrombus with pulmonary embolism complicating amebic liver
      abscess.

PMID- 23949991
TI  - Cartilage hair hypoplasia and celiac disease: report of an Indian girl with novel
      genotype.
AB  - Cartilage hair hypoplasia is a genetic disease, characterized by generalized
      metaphyseal dysplasia mainly affecting the knee joints. Variable extraskeletal
      features like anemia, malabsorption, impaired spermatogenesis, impaired immunity,
      and malignancies have been reported. The work up of malabsorption and short
      stature led to the diagnosis of celiac disease in three previous cases of
      cartilage hair hypoplasia. Here, we report an Indian girl with a novel genotype,
      diagnosed as celiac disease with cartilage hair hypoplasia, and review the
      previous three cases. 

PMID- 23949992
TI  - Microbial monomers custom-synthesized to build true bio-derived aromatic
      polymers.
AB  - Aromatic polymers include novel and extant functional materials although none has
      been produced from biotic building blocks derived from primary biomass glucose.
      Here we screened microbial aromatic metabolites, engineered bacterial metabolism
      and fermented the aromatic lactic acid derivative beta-phenyllactic acid (PhLA).
      We expressed the Wickerhamia fluorescens gene (pprA) encoding a phenylpyruvate
      reductase in Escherichia coli strains producing high levels of phenylalanine, and
      fermented optically pure (>99.9 %) D-PhLA. Replacing pprA with bacterial ldhA
      encoding lactate dehydrogenase generated L-PhLA, indicating that the produced
      enzymes converted phenylpyruvate, which is an intermediate of phenylalanine
      synthesis, to these chiral PhLAs. Glucose was converted under optimized
      fermentation conditions to yield 29 g/l D-PhLA, which was purified from
      fermentation broth. The product satisfied the laboratory-scale chemical synthesis
      of poly(D-PhLA) with M w 28,000 and allowed initial physiochemical
      characterization. Poly(D-PhLA) absorbed near ultraviolet light, and has the same
      potential as all other biomass-derived aromatic bioplastics of phenylated
      derivatives of poly(lactic acid). This approach to screening and fermenting
      aromatic monomers from glucose exploits a new era of bio-based aromatic polymer
      design and will contribute to petroleum conservation and carbon dioxide fixation.

PMID- 23949993
TI  - Structural characteristics of thermostable immunogenic outer membrane protein
      from Salmonella enterica serovar Typhi.
AB  - In this work, we explored the acid-induced unfolding pathway of non-porin outer
      membrane protein (OMP), an immunogenic protein from Salmonella Typhi, by
      monitoring the conformational changes over a pH range of 1.0-7.0 by circular
      dichroism, intrinsic fluorescence, ANS binding, acrylamide quenching, and dynamic
      light scattering. The spectroscopic measurements showed that OMP in its native
      state at pH 7.0 exists in more stable and compact conformation. In contrast, at
      pH 2.0, OMP retains substantial amount of secondary structure, disrupted side
      chain interactions, increased hydrodynamic radii, and nearly four-fold increase
      in ANS fluorescence with respect to the native state, indicating that MG state
      exists at pH 2.0. Quenching of tryptophan fluorescence by acrylamide further
      confirmed the accumulation of a partially unfolded state between native and
      unfolded state. The effect of pH on the conformation and thermostability of OMP
      points towards its heat resistance at neutral pH (T m ~ 69  degrees C at pH 7.0,
      monitored by change in MRE222 nm). Acid unfolded state was also characterized by
      the lack of a cooperative thermal transition. All these results suggested that
      acid-induced unfolded state of OMP at pH 2.0 represented the molten globule
      state. The chemical denaturation studies with GuHCl and urea as denaturants
      showed dissimilar results. The chemical unfolding experiments showed that in both
      far-UV CD and fluorescence measurements, GuHCl is more efficient than urea. GuHCl
      is characterized by low C m (~1 M), while urea is characterized by high C m (~3
      M). The fully unfolded states were reached at 2 M GuHCl and 4 M urea
      concentration, respectively. This study adds to several key considerations of
      importance in the development of therapeutic agents against typhoid fever for
      clinical purposes.

PMID- 23949994
TI  - Mineralization of 4-fluorocinnamic acid by a Rhodococcus strain.
AB  - A bacterial strain capable of aerobic degradation of 4-fluorocinnamic acid (4
      FCA) as the sole source of carbon and energy was isolated from a biofilm reactor
      operating for the treatment of 2-fluorophenol. The organism, designated as strain
      S2, was identified by 16S rRNA gene analysis as a member of the genus
      Rhodococcus. Strain S2 was able to mineralize 4-FCA as sole carbon and energy
      source. In the presence of a conventional carbon source (sodium acetate [SA]),
      growth rate of strain S2 was enhanced from 0.04 to 0.14 h(-1) when the culture
      medium was fed with 0.5 mM of 4-FCA, and the time for complete removal of 4-FCA
      decreased from 216 to 50 h. When grown in SA-supplemented medium, 4-FCA
      concentrations up to 1 mM did not affect the length of the lag phase, and for 4
      FCA concentrations up to 3 mM, strain S2 was able to completely remove the target
      fluorinated compound. 4-Fluorobenzoate (4-FBA) was transiently formed in the
      culture medium, reaching concentrations up to 1.7 mM when the cultures were
      supplemented with 3.5 mM of 4-FCA. Trans,trans-muconate was also transiently
      formed as a metabolic intermediate. Compounds with molecular mass compatible with
      3-carboxymuconate and 3-oxoadipate were also detected in the culture medium.
      Strain S2 was able to mineralize a range of other haloorganic compounds,
      including 2-fluorophenol, to which the biofilm reactor had been exposed. To our
      knowledge, this is the first time that mineralization of 4-FCA as the sole carbon
      source by a single bacterial culture is reported.

PMID- 23949995
TI  - Functional genes (dsr) approach reveals similar sulphidogenic prokaryotes
      diversity but different structure in saline waters from corroding high
      temperature petroleum reservoirs.
AB  - Oil reservoirs and production facilities are generally contaminated with H2S
      resulting from the activity of sulphidogenic prokaryotes (SRP). Sulphidogenesis
      plays a major role in reservoir souring and microbial influenced corrosion in oil
      production systems. In the present study, sulphidogenic microbial diversity and
      composition in saline production fluids retrieved from three blocks of corroding
      high temperature (79 ~ 95  degrees C) oil reservoirs with high sulfate
      concentrations were investigated by phylogenetic analyses of gene fragments of
      the dissimilatory sulfite reductase (dsr). Analysis of dsr gene fragments
      revealed the presence of several clusters of sulphidogenic prokaryotes that cover
      the orders Desulfovibrionales (Desulfovibrio, Desulfomicrobium thermophilum),
      Desulfobacterales (Desulfobacterium, Desulfosarcina, Desulfococcus,
      Desulfotignum, Desulfobotulus, Desulfobulbus), Syntrophobacterales (Desulfacinum,
      Thermodesulforhabdus, Desulforhabdus), Clostridiales (Desulfotomaculum) and
      Archaeoglobales (Archaeoglobus); among which sequences affiliated to members of
      Desulfomicrobium, Desulfotomaculum and Desulfovibrio appeared to be the most
      encountered genera within the three blocks. Collectively, phylogenetic and non
      metric multidimensional scaling analyses indicated similar but structurally
      different sulphidogenic prokaryotes communities within the waters retrieved from
      the three Blocks. This study show the diversity and composition of sulphidogenic
      prokaryotes that may play a role in the souring mediated corrosion of the
      oilfield and also provides a fundamental basis for further investigation to
      control oil reservoir souring and corrosion of pipelines and topside
      installations.

PMID- 23949996
TI  - Insect protein digestion improves purity of Steinernema carpocapsae in vitro
      culture and reduces culture period.
AB  - Insect protein, used for in vitro culture media for entomopathogenic nematode,
      produces nematodes of high quality. However, the time-consuming culture and poor
      purity of nematodes hinder the commercial application of insect protein media. We
      show that hydrolyzed insect protein improves nematode purity in in vitro culture.
      The results revealed that nematode purity was increased by more than 90 %, and
      the culture period was reduced by 6 days. Estimated economic efficiency of using
      hydrolyzed insect protein medium was increased by 44.25 % over that obtained with
      non-hydrolyzed insect medium. 

PMID- 23949997
TI  - Camptothecin-producing endophytic fungus Trichoderma atroviride LY357: isolation,
      identification, and fermentation conditions optimization for camptothecin
      production.
AB  - Camptothecin (CPT), the third largest anticancer drug, is produced mainly by
      Camptotheca acuminata and Nothapodytes foetida. CPT itself is the starting
      material for clinical CPT-type drugs, but the plant-derived CPT cannot support
      the heavy demand from the global market. Research efforts have been made to
      identify novel sources for CPT. In this study, three CPT-producing endophytic
      fungi, Aspergillus sp. LY341, Aspergillus sp. LY355, and Trichoderma atroviride
      LY357, were isolated and identified from C. acuminata. Most CPT produced by these
      fungi was found in the fermentation broth, and their corresponding CPT yields
      were 7.93, 42.92, and 197.82 MUg l(-1), respectively. The CPT-producing
      capability of LY341 and LY355 was completely lost after repeat subculturing. A
      substantial decrease of CPT production was also observed in the second generation
      of LY357. However, a stable and sustainable production of CPT was found from the
      second generation through the eighth generation of LY357. The fermentation
      medium, time, pH, temperature, and agitation rate were optimized for CPT
      production. Methyl jasmonate and XAD16 were proven to be an optimum elicitor and
      adsorbent resin, respectively, in view of that CPT yield was increased 3.4- and
      11-fold through their use. A 50- to 75-fold increase of CPT yield was obtained
      when the optimized fermentation conditions, elicitor, and adsorbent resin were
      combined and applied to the culture of the seventh and eighth generations of
      LY357, and the highest CPT yield was 142.15 MUg l(-1). The CPT-producing T.
      atroviride LY357 paves a potential to uncover the mysteries of CPT biosynthesis.

PMID- 23949998
TI  - Abundance and community structure of ammonia-oxidizing microorganisms in
      reservoir sediment and adjacent soils.
AB  - Ammonia oxidation is an important process for global nitrogen cycling. Both
      ammonia-oxidizing bacteria (AOB) and archaea (AOA) can be the important players
      in nitrification process. However, their relative contribution to nitrification
      remains controversial. This study investigated the abundance and community
      structure of AOA and AOB in sediment of Miyun Reservoir and adjacent soils.
      Quantitative PCR assays indicated that the highest AOA abundance occurred in
      unplanted riparian soil, followed by reservoir sediment, reed-planted riparian
      soil and agricultural soil. The AOB community size in agricultural soil was much
      larger than that in the other habitats. Large variations in the structures of AOA
      and AOB were also observed among the different habitats. The abundance of
      Nitrosospira-like AOB species were detected in the agricultural soil and
      reservoir sediment. Pearson's correlation analysis showed the AOB diversity had
      positive significant correlations with pH and total nitrogen, while the AOA
      diversity might be negatively affected by nitrate nitrogen and ammonia nitrogen.
      This work could add new insights towards nitrification in aquatic and terrestrial
      ecosystems. 

PMID- 23949999
TI  - Graphene-regulated cardiomyogenic differentiation process of mesenchymal stem
      cells by enhancing the expression of extracellular matrix proteins and cell
      signaling molecules.
AB  - The potential of graphene as a mesenchymal stem cell (MSC) culture substrate to
      promote cardiomyogenic differentiation is demonstrated. Graphene exhibits no sign
      of cytotoxicity for stem cell culture. MSCs are committed toward cardiomyogenic
      lineage by simply culturing them on graphene. This may be attributed, at least
      partially, to the regulation of expression levels of extracellular matrix and
      signaling molecules. 

PMID- 23950000
TI  - A transient myelodysplastic/myeloproliferative neoplasm in a patient with cardio
      facio-cutaneous syndrome and a germline BRAF mutation.
AB  - A male infant, born at 32 weeks gestation by cesarean because of hydrops fetalis,
      presented with multiple anomalies, such as sparse and curly scalp hair, absent
      eyebrows, frontal bossing, an atrial septal defect, pulmonary artery stenosis,
      and whole myocardial thickening. He was clinically diagnosed with cardio-facio
      cutaneous (CFC) syndrome, and was confirmed to have a germline V-raf murine
      sarcoma viral oncogene homologue B1 (BRAF) c.721 A>C mutation. At 1 month of age,
      he presented with a transient myelodysplastic/myeloproliferative neoplasm
      (MDS/MPN), which improved within a month without the administration of
      antineoplastic agents. This is the first report of CFC syndrome with MDS/MPN. The
      coexistence of MDS/MPN may be related to this BRAF c.721 A>C mutation.

PMID- 23950002
TI  - Methyl jasmonate increases the tropane alkaloid scopolamine and reduces natural
      herbivory in Brugmansia suaveolens: is scopolamine responsible for plant
      resistance?
AB  - The tropane alkaloid (TA) scopolamine is suggested to protect Brugmansia
      suaveolens (Solanaceae) against herbivorous insects. To test this prediction in a
      natural environment, scopolamine was induced by methyl jasmonate (MJ) in potted
      plants which were left 10 days in the field. MJ-treated plants increased their
      scopolamine concentration in leaves and herbivory decreased. These findings
      suggest a cause-effect relationship. However, experiments in laboratory showed
      that scopolamine affect differently the performance of the specialist larvae of
      the ithomiine butterfly Placidina euryanassa (C. Felder & R. Felder) and the
      generalist fall armyworm Spodoptera frugiperda (J. E. Smith): the specialist that
      sequester this TA from B. suaveolens leaves was not negatively affected, but the
      generalist was. Therefore, scopolamine probably acts only against insects that
      are not adapted to TAs. Other compounds that are MJ elicited may also play a role
      in plant resistance against herbivory by generalist and specialist insects, and
      deserve future investigations. 

PMID- 23950003
TI  - Spatial behavior comparison of Bactericera Cockerelli Sulc. (hemiptera:
      triozidae) in Mexico.
AB  - During the last five years, Bactericera cockerelli Sulc. has caused significant
      economic losses in potato production in Mexico, due to the purple top and zebra
      chip diseases, since it acts as the vector of Candidatus Liberibacter
      psyllaurous. Despite its importance as a vector of serious potato diseases, the
      knowledge of its spatial distribution behavior, which could improve the
      efficiency of control measures, is entirely lacking. The main objective of this
      work was to compare the spatial distribution of the immature and adult stages of
      B. cockerelli obtained in a potato field by means of transect and quadrant
      sampling techniques and of geostatistics tools that allow the visualization of
      its spatial distribution in the field. Transect and quadrant samplings showed
      that the immature stages (eggs and nymphs) of B. cockerelli present a clustered
      distribution. The validation of the achieved semivariograms in the three dates of
      sampling corroborated the aggregated distribution of immatures and adults of the
      insect. The maps obtained in the sampling by using the quadrant or the transect
      approaches reflect the aggregated structure of the insect populations which did
      not infest 100% of the plot area. This allowed us to identify infested and free
      areas, what will aid in decisions for selecting alternatives of control.

PMID- 23950004
TI  - Temporal variation in seed predation by insects in a population of Syagrus
      romanzoffiana (Arecaceae) in Santa Catarina Island, SC, Brazil.
AB  - Insect seed predation may vary depending on seed production. The present study
      considers the hypothesis that the rates of seed predation tend to be smaller in
      years of higher fruit production. Thus, we monitored the production of fruits and
      predation of seeds of the palm Syagrus romanzoffiana over 2 years in the Atlantic
      Forest (Parque Municipal da Lagoa do Peri, Florianopolis, SC, Brazil), between
      July 2006 and June 2008. Plots of 0.25 m(2) were fitted under 20 mother plants
      and fruits were monthly collected for assessment of abundance and seed predation.
      There was variation in fruit production between the 2 years and among
      reproductive plants. Predation rates were high and occurred in the predispersal
      phase by the Curculionidae Revena rubiginosa Boheman, Anchylorhynchus aegrotus
      Fahraeus, and Anchylorhynchus variabilis Gyllenhal. Seed predation by these
      species of Anchylorhynchus is first registered in the present study. In average,
      about 60% of the seeds monthly produced in the population tend to escape insect
      predation in year of high or low production, becoming available for recruitment.
      The predation rate was not related to the amount of fruits produced per
      reproductive plant. Also, different than expected, there was a positive relation
      between the rates of seed predation and the total of fruits produced monthly on
      the plots. Thus, no evidence for the satiation of insect seed predators was found
      in this study with S. romanzoffiana. 

PMID- 23950005
TI  - Fall Armyworm, spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae),
      female moths respond to herbivore-induced corn volatiles.
AB  - In response to herbivore attack, plants release herbivore-induced plant volatiles
      (HIPVs) that represent important chemical cues for herbivore natural enemies.
      Additionally, HIPVs have been shown to mediate other ecological interactions with
      herbivores. Differently from natural enemies that are generally attracted to
      HIPVs, herbivores can be either attracted or repelled depending on several
      biological and ecological parameters. Our study aimed to assess the olfactory
      response of fall armyworm-mated female moths toward odors released by
      mechanically and herbivore-induced corn at different time intervals. Results
      showed that female moths strongly respond to corn volatiles, although fresh
      damaged corn odors (0-1 h) are not recognized by moths. Moreover, females
      preferred volatiles released by undamaged plant over herbivore-induced plants at
      5-6 h. This preference for undamaged plants may reflect an adaptive strategy of
      moths to avoid competitors and natural enemies for their offspring. We discussed
      our results based on knowledge about corn volatile release pattern and raise
      possible explanations for fall armyworm moth behavior.

PMID- 23950006
TI  - Succession of carrion fauna in the arid region of San Juan Province, Argentina
      and its forensic relevance.
AB  - The succession of carrion fauna and the decomposition stages were studied in the
      arid environment of San Juan Province, Argentina (31 degrees 32'34.7" S; 68
      degrees 34'39.4" W). Two pig carcasses (Sus scrofa) were placed in wire mesh
      cages, 100 m apart from each other. Each carcass was surrounded by pitfall traps,
      and a modified Malaise trap was placed above. Daily samplings were carried out to
      collect the insects present in the carcasses and the traps, and body and
      environmental temperature were measured. The main colonizer species was Chrysomya
      albiceps (Wiedemann) and its larvae were dominant over other Diptera. The first
      adult blowflies emerged at 8.9 days. The time to reach the remains stage was 8
      days shorter than for other South American sites. We recorded the early arrival
      of adult Dermestes maculates De Geer and Dermestes ater De Geer 2 days after the
      beginning of the assay, and larvae of these species were recorded 4 days after.
      We determined a 1.5-day error in the postmortem interval estimation using the
      temperatures measured in the assay and those recorded by the nearest
      meteorological station.

PMID- 23950007
TI  - Drosophilid assemblages at different urbanization levels in the city of Porto
      Alegre, state of Rio Grande do Sul, southern Brazil.
AB  - The present study analyzed the drosophilid assemblages in different levels of
      urbanization in the city of Porto Alegre, Rio Grande do Sul, Brazil. Collections
      were carried out in 2008 in three different environments: a highly urbanized area
      "Jardim Botanico," a forested area with intermediary urbanization-"Parque Gabriel
      Knijnik," and in a relatively well-preserved forested area, although threatened
      by the urban growth-"Morro Santana." In Jardim Botanico, 36 species belonging to
      four genera were found, with high abundance of exotic species as Drosophila
      simulans Sturtevant and Zaprionus indianus (Gupta). In Parque Gabriel Knijnik, 33
      species that belonged to four genera were found, with higher abundances of native
      species belonging to the Drosophila tripunctata species group and Drosophila
      willistoni species subgroup, and lower abundance of exotic species. As for Morro
      Santana, 32 species and three genera were found, with higher abundances of native
      groups, low representativeness of exotic species, and absence of Zaprionus
      indianus. The analysis of the Jaccard index showed higher similarity in the
      species composition between samples collected in summer and autumn, and between
      samples collected in winter and spring. On the other hand, the Morisita index
      differentiated Jardim Botanico from the other two studied sites. Our results show
      that Morro Santana is an important area of native biodiversity, reinforcing,
      therefore, the inclusion of this area in the project for the creation of an
      ecological corridor as proposed by the Ministry of the Environment of Brazil. 

PMID- 23950008
TI  - Number of malpighian tubules in larvae and adults of stingless bees (Hymenoptera:
      Apidae) from Amazonia.
AB  - The number of Malpighian tubules in larvae and adults of bees is variable. Larvae
      of Apis mellifera L. have four Malpighian tubules, while adults have 100 tubules.
      In stingless bees, this number varies from four to eight. The objectives of this
      study were to provide characteristics of the Malpighian tubules as well as to
      quantify their number in larvae and adults of six species of Meliponinae,
      Melipona seminigra merrillae Cockerell, Melipona compressipes manaosensis
      Schwarz, Melipona rufiventris Lepeletier, Scaptotrigona Moure, Frieseomelitta
      Ihering, and Trigona williana Friese. Malpighian tubules were dissected from
      larvae and adults, measured, quantified, and maintained in microtubes with
      Dietrich's solution. The numbers of Malpighian tubules were constant only for
      larvae of M. rufiventris (four and eight) and Scaptotrigona sp. (four). The most
      frequent number of tubules in the Melipona group was seven and eight in larvae,
      and 70 and 90 in adults. In the Trigona group were four and 20 to 40, for larvae
      and adults, respectively. The results showed differences in the number of
      Malpighian tubules among the species analyzed and also between the larvae and
      adults of the same species. Despite the variation observed, species of the group
      Melipona always have a larger number and longer Malpighian tubules in both larvae
      and adults as compared to the Trigona group, which may indicate an evolutionary
      trend of differentiation between these groups. 

PMID- 23950009
TI  - The diversity of flower flies (Diptera: syrphidae) in Colombia and their
      neotropical distribution.
AB  - In Colombia, like most Neotropical countries, faunistic studies on flower flies
      have been occasional and most of them have been primarily focused on taxonomy.
      Colombia is the second-most species-rich country in flower fly diversity in the
      Neotropics after Brazil, and has one of the highest numbers of species per unit
      area (2.49 per 10,000 km2), based on a review of literature and national
      collections. Including new data presented here, a total of 47 genera and 300
      species are recorded in Colombia. The genera Scaeva Fabricius and Lycastrirhyncha
      Bigot, as well as 101 species are recorded here for the first time. The
      altitudinal range and the distribution of the flower fly genera in Colombia are
      presented. A preliminary comparison of the fauna of Colombia with that of other
      Neotropical countries is given. A historical perspective is also provided in
      order to illustrate how Colombian Syrphidae knowledge has progressed over the
      last 168 years. Information presented here will be useful for ongoing and future
      biodiversity research as well as conservation projects on Syrphidae in the
      Neotropical region.

PMID- 23950010
TI  - Occurrence of three haplotypes of Linepithema micans (Forel) (Hymenoptera:
      Formicidae) in Southern Brazil.
AB  - Linepithema micans (Forel) (Hymenoptera: Formicidae) is reported to occur from
      eastern Brazil to central Argentina in pasture or grassland, forest and second
      growth riparian forest, nesting under stones, rotting wood, and sandy soil.
      However, information on this species is poor and its ecological interactions and
      role as pests are unknown. Linepithema humile (Mayr), a closely related species
      to L. micans, known as the Argentine ant, is native to South America, and was
      accidentally introduced to several regions of the world. Recent studies have
      shown that other related species, such as L. micans, could become as pestiferous
      as L. humile because of its phylogenetic proximity. Samples of L. micans from
      different habitats in Southern Brazil were characterized by sequencing of the
      mitochondrial DNA. Sequences were compared to previously obtained sequences from
      samples of L. humile and the genetic distance and differences in the tRNALeu
      structure were investigated. Our data identified three haplotypes of L. micans,
      two of which were observed in ant populations closely associated with the
      Brazilian ground pearl Eurhizococcus brasiliensis (Hempel) (Hemiptera:
      Margarodidae), a soil scale that is a serious pest of vineyards. The third
      haplotype was identified in ants from populations invading residences in urban
      habitats. 

PMID- 23950011
TI  - Activity of a Brazilian strain of Bacillus thuringiensis israelensis against the
      cotton Boll Weevil Anthonomus grandis Boheman (Coleoptera: Tenebrionidae).
AB  - A Brazilian Bacillus thuringiensis subspecies israelensis, toxic to Diptera,
      including mosquitoes, was found also to show toxicity to the coleopteran boll
      weevil Anthonomus grandis Boheman at an equivalent level to that of the standard
      coleopteran-active B. thuringiensis subspecies tenebrionis T08017. Recombinant B.
      thuringiensis strains expressing the individual Cyt1Aa, Cry4Aa, Cry4Ba and
      Cry11Aa toxins from this strain were assessed to evaluate their potential
      contribution to the activity against A. grandis, either alone or in combination.
      Whilst individual toxins produced mortality, none was sufficiently potent to
      allow calculation of LC50 values. Combinations of toxins were unable to attain
      the same potency as the parental B. thuringiensis subsp. israelensis, suggesting
      a major role for other factors produced by this strain. 

PMID- 23950012
TI  - The impact of industrial anthropization on mosquito (Diptera, Culicidae)
      communities in mangrove areas of Guanabara Bay (Rio de Janeiro, Brazil).
AB  - The effects of industrial anthropization on species composition and community
      diversity of Culicidae (Diptera) were studied in a mangrove area impacted by
      industrial activities as compared to a preserved area, both around Guanabara Bay
      in the state of Rio de Janeiro, Brazil. Diversity, equitability, and species
      richness in Culicidae community differed between the studied areas. Indicator
      species analysis and correspondence analysis were carried out and indicated that
      the Sabethini, especially Wyeomyia (Phoniomyia) theobaldi Lane, Wyeomyia
      (Phoniomyia) fuscipes (Edwards), and a non-identified species of Wyeomyia sp.
      were associated to the preserved area, whereas Aedes taeniorhynchus Wiedemann and
      Aedes scapularis (Rondani) to the impacted area. 

PMID- 23950013
TI  - Ornithodoros peruvianus Kohls, Clifford & Jones (Ixodoidea: Argasidae) in Chile:
      a tentative diagnosis.
AB  - Three argasid tick larvae were collected on April 2, 2010, from a common vampire
      bat, Desmodus rotundus, captured in the Parque Nacional Pan de Azucar (26 degrees
      09' S, 70 degrees 41' W), Region of Atacama, Chile. The larvae were diagnosed as
      Ornithodoros, and further comparative analysis showed them to be Ornithodoros
      peruvianus Kohls, Clifford & Jones or a species close to it. Phylogenetic
      analysis based on 16S mitochondrial rRNA gene sequences of Ornithodoros species
      plus four Argas species was carried out to clarify the taxonomic position of the
      larvae. This is the first finding of ticks parasitizing D. rotundus in Chile. 

PMID- 23950014
TI  - First Record of Edessa meditabunda (F.) on Lettuce in Mato Grosso State, Brazil.
AB  - We report the first record of the stink bug Edessa meditabunda (F.) on lettuce
      Lactuca sativa in the organic vegetable garden "Cheiro Verde" in Tangara da
      Serra, State of Mato Grosso, Brazil (14 degrees 37'13" S, 57 degrees 28'46" W).
      During September, October, and November 2009, we collected 1,099 adults, 43
      nymphs, and 29 egg masses. Feeding by this stink bug possibly caused early
      bolting. 

PMID- 23950015
TI  - Occurrence of Stiretrus decastigmus (Herrich-Schaeffer) (Hemiptera: Pentatomidae)
      preying on Microtheca semilaevis Stal (Coleoptera: Chrysomelidae).
AB  - Microtheca semilaevis Stal is a phythophagous insect associated to Brassicaceae,
      and frequently occurs with other species of beetles, such as Microtheca ochroloma
      Stal. Despite its importance to organic farmers, there is no information in the
      Brazilian literature about its natural enemies. Stiretrus decastigmus (Herrich
      Schaeffer) was first found and here reported preying an adult of M. semilaevis in
      Chinese cabbage in Santa Maria, RS, Brazil (29 degrees 43'28"S, 53 degrees
      43'19"W). 

PMID- 23950016
TI  - Human dental pulp stem cells derived from cryopreserved dental pulp tissues of
      vital extracted teeth with disease demonstrate hepatic-like differentiation.
AB  - Reviewing the literature, hepatic differentiation of human dental pulp stem cells
      (hDPSCs) from cryopreserved dental pulp tissues of vital extracted teeth with
      disease has not been studied. This study is aimed to evaluate the hypothesis that
      hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with
      disease could possess potential hepatic differentiation. Forty vital extracted
      teeth with disease recruited for hDPSCs isolation, stem cell characterization and
      hepatic differentiation were randomly and equally divided into group A (liquid
      nitrogen-stored dental pulp tissues) and group B (freshly derived dental pulp
      tissues). Samples of hDPSCs isolated from groups A and B but without hepatic
      growth factors formed negative controls. A well-differentiated hepatocellular
      carcinoma cell line was employed as a positive control. All the isolated hDPSCs
      from groups A and B showed hepatic-like differentiation with morphological change
      from a spindle-shaped to a polygonal shape and normal karyotype. Differentiated
      hDPSCs and the positive control expressed hepatic metabolic function genes and
      liver-specific genes. Glycogen storage of differentiated hDPSCs was noted from
      day 7 of differentiation-medium culture. Positive immunofluorescence staining of
      low-density lipoprotein and albumin was observed from day 14 of differentiation
      medium culture; urea production in the medium was noted from week 6. No hepatic
      differentiation was observed for any of the samples of the negative controls. We
      not only demonstrated the feasibility of hepatic-like differentiation of hDPSCs
      from cryopreserved dental pulp tissues of vital extracted teeth with disease but
      also indicated that the differentiated cells possessed normal karyotype and were
      functionally close to normal hepatic-like cells. Copyright (c) 2013 John Wiley &
      Sons, Ltd.

PMID- 23950017
TI  - 5q31.3 Microdeletion syndrome: clinical and molecular characterization of two
      further cases.
AB  - The 5q31.3 microdeletion syndrome has recently emerged as a distinct clinical
      entity, and we report two new patients with de novo deletions of this region,
      bringing the total to seven. Similarly to previously reported cases, the
      phenotype of our patients is characterized by marked hypotonia, apnea,
      developmental delay, and feeding difficulties. Both patients had abnormal
      movements which did not correlate with epileptiform activity on
      electroencephalogram (EEG). Developmental brain changes on neuroimaging consisted
      of abnormalities predominantly affecting the white matter and frontal lobes. The
      5q31.3 deleted regions overlap those of previously reported cases, and allow
      further refinement of the shortest region of overlap to 101 kb, including only
      three genes. Of these, the purine-rich element binding protein A (PURA) gene has
      an established role in brain development, and we propose that haploinsufficiency
      for this gene is primarily responsible for the neurodevelopmental features
      observed.

PMID- 23950018
TI  - Multiwalled carbon nanotubes hinder microglia function interfering with cell
      migration and phagocytosis.
AB  - The intranasal drug delivery route provides exciting expectations regarding the
      application of engineered nanomaterials as nano-medicines or drug-delivery
      vectors into the brain. Among nanomaterials, multiwalled CNTs (MWCNTs) are some
      of the best candidates for brain cancer therapy since they are well known to go
      across cellular barriers and display an intrinsic ability to block cancer cell
      proliferation triggering apoptosis. This study reveals that microglial cells, the
      brain macrophages and putative vehicles for MWCNTs into the brain, undergo a dose
      dependent cell division arrest and apoptosis when treated with MWCNTs. Moreover,
      it is shown that MWCNTs severely interfere with both cell migration and
      phagocytosis in live microglia. These results lead to a re-evaluation of the
      safety of inhaled airborne CNTs and provide strategic clues of how to
      biocompatibilize MWCNTs to reduce brain macrophage damage and to develop new
      nanodrugs. 

PMID- 23950019
TI  - The role of corticolimbic circuitry in the development of anxiety disorders in
      children and adolescents.
AB  - Although most individuals progress through the periods of childhood and
      adolescence without significant disturbance, these developmental stages encompass
      the peak onset times for many forms of psychopathology related to altered emotion
      regulation, including anxiety disorders. Understanding the development of neural
      circuitry associated with emotion regulation may provide important insights into
      risk factors for psychopathology and how disturbances in function arise. The
      amygdala and ventral prefrontal cortex are two major nodes of a corticolimbic
      circuit involved in processing and regulating responses to emotional stimuli. We
      begin this chapter by reviewing evidence from diffusion tensor imaging and
      functional magnetic resonance imaging suggesting that changes in the structure
      and function of this circuitry occur during typical development in childhood and
      adolescence. Next, we discuss research on the function of this circuitry in
      pediatric anxiety disorder patients, and how abnormalities may be related to
      altered neural development. Finally, we illustrate a model for the role of
      corticolimbic circuitry in examining the development of anxiety disorders by
      discussing how the structure and function of this circuitry can serve as a neural
      mediator for linking genetic and environmental influences to the development of
      anxiety disorders. This model has the potential to inform our understanding of
      why anxiety disorders typically onset during childhood and adolescence and
      provides future directions for research that may allow us to better predict or
      prevent their development..

PMID- 23950021
TI  - Aspisoma lineatum (Gyllenhal) (Coleoptera: Lampyridae) firefly: description of
      the immatures, biological, and ecological aspects.
AB  - Aspisoma lineatum (Gyllenhal) is a common firefly in the Southeastern region of
      Brazil. Adults and larvae were collected in the municipality of Campinas, state
      of Sao Paulo, Brazil, and the immature stages were described and reared in the
      laboratory. Four generations were reproduced in the laboratory, and a method for
      its rearing was established. The life cycle usually lasts 6 months, but under
      optimal laboratory conditions, it lasted from 2 to 4 months. Larvae were fed with
      Bradybaena similaris and Bulimulus tenuissimus snails since the beginning of the
      larval stage. This species was found to be easily adapted to environments under
      anthropic influence, such as urban areas and farms.

PMID- 23950020
TI  - High abundance of neotropical drosophilids (Diptera: Drosophilidae) in four
      cultivated areas of central Brazil.
AB  - The drosophilid assemblages of four cultivated areas (soy, bean, corn, and orange
      plantations) grown in the core of the Neotropical region were analyzed by
      comparing their abundances and compositions. The collections, which were gathered
      using 38 banana traps, captured 12,560 drosophilids, including nine Neotropical
      and six exotic species. Most of the flies were collected in the bean (43%) and
      soy (42%) fields. The composition and relative abundance of species also varied
      among cultivated areas, with orange orchards presenting the highest relative
      abundance of exotics due to the dominance of the Afrotropical Zaprionus indianus
      (Gupta). Crop plantations were dominated by a Neotropical species, Drosophila
      cardini (Sturtevant), which has been shown to be well adapted to dry and
      disturbed environments. We discuss the drosophilid assemblages of the cultivated
      areas, comparing them with assemblages from neighbor urban and natural
      environments. The low drosophilid richness found in this study is similar to the
      richness found in urban environments and lower than the drosophilid richness of
      forests, supporting a pattern already known for other taxa. The high abundance of
      drosophilids in cultivated areas, as well as the dominance of a Neotropical
      species (D. cardini) in the crop assemblages, was a surprising result.

PMID- 23950022
TI  - Effect of biotic factors on the spatial distribution of stingless bees
      (Hymenoptera: Apidae, Meliponini) in fragmented neotropical habitats.
AB  - We recorded stingless bee colony abundance and nesting habits in three sites with
      different anthropogenic activities in the Soconusco region of Chiapas, Mexico:
      (1) agroforestry (7 hacacao crop), (2) grassland (12 ha), and (3) urban area (3
      ha). A total of 67 nests were found, representing five stingless bee species,
      Tetragonisca angustula angustula (Lepeletier), Trigona fulviventris (Guerin),
      Scaptotrigona mexicana (Guerin), Scaptotrigona pectoralis (Dalla Torre), and
      Oxytrigona mediorufa (Cockerell). The most abundant stingless bee in each site
      was T. angustula angustula (>50%). The primary tree species used by the bees were
      Ficus spp. (Moraceae, 37.8%) and Cordia alliodora (Boraginaceae, 13.5%). The nest
      entrance height of T. angustula angustula (96 +/- 19 cm) was different than the
      other species, and this bee was the only one that used all different nesting
      sites. Volatiles analyzed by gas chromatography from pollen collected by the
      stingless bees differed between bee species, but were highly similar in respect
      to the fragrances of the pollen collected by the same species at any site. Our
      data indicate that T. angustula angustula experienced low heterospecific and high
      intraspecific foraging overlap especially in the urban site. We observed cluster
      spatial distribution in grassland and in agroforestry sites. In the urban site,
      T. angustula angustula presented random distribution tended to disperse. Trigona
      fulviventris was the only overdispersed and solitary species.

PMID- 23950023
TI  - Influence of the orientation of nest entrance, shading, and substrate on sampling
      trap-nesting bees and wasps.
AB  - The use of trap nests supplies important biological information concerning the
      biology of bees and wasps. However, the knowledge about the factors that
      influence the management of these groups is still scarce. Our study aimed to
      analyze the effects of the orientation of nest entrance, shading, and block
      material (wood or vermiculite) on the frequency, richness, and composition of
      trap-nesting species at two agricultural areas in the Atlantic Forest region of
      the state of Paraiba. Both sites showed similar species richness and composition.
      However, a higher number of nests was found at the Alhandra site, mainly of the
      species Trypoxylon aurifrons Shuckard and Centris analis (F.). Regarding the
      orientation, the number of nest entrances oriented to prevailing wind direction
      was significantly smaller. Most species nested more frequently in shaded areas
      than in sunny areas and the wood blocks were more attractive than the vermiculite
      blocks, especially for bees.

PMID- 23950025
TI  - Argentinean species of Chalarus Walker (Diptera: Pipunculidae): new records and
      description of Chalarus tani n. sp.
AB  - The Argentinean species of Chalarus Walker were studied. Pipunculidae adults
      belonging to four species, C halarus chilensis Collin, Chalarus triramosus
      Rafael, Chalarus absonus Rafael and Chalarus tani n. sp. were described based on
      two male specimens collected in the La Rioja and Tucuman Provinces, northwestern
      region of Argentina. Chalarus absonus is recorded for the first time in
      Argentina. New distributional data and an identification key to the adult males
      of the Argentinean representatives are provided including figures.

PMID- 23950024
TI  - Courtship behavior of Zaprionus indianus (Gupta) (Diptera: Drosophilidae) from
      populations colonizing South America.
AB  - We describe for the first time the sexual behavior and the courtship song of
      males of the African fly Zaprionus indianus (Gupta), a recent invader of South
      America. The male courtship song is formed by monocyclic pulses and the courtship
      behavior is simple when compared to that of species of Drosophila. Two interpulse
      interval (IPI) distributions were observed: pre-mounting and mounting. No
      significant difference was observed between the pre-mounting IPIs of males that
      descended from three geographical populations from South America. We also
      observed the songs produced by females and the homosexual behavior exhibited by
      males. A sequence of bursts is produced by females as a refusal signal against
      males, while males emit a characteristic song that identifies sex genus, which
      differs from the courtship song. The short courtship and mating latencies
      recorded reveal vigorous males and receptive females, respectively.

PMID- 23950026
TI  - New World Stictocladius Edwards (Diptera: Chironomidae).
AB  - The orthocladiine Chironomidae genus Stictocladius Edwards was described
      originally from South America. Although recognised subsequently as present also
      in Australia and New Zealand, the true diversity in the Neotropics has remained
      unclear. After more than a decade of collections of both isolated adults and
      aquatic immature stages, we can recognise several new taxa and associate some
      immature stages. Thus, we describe Stictocladius prati n. sp. as male, female,
      pupa and larva; Stictocladius acutus n. sp. and Stictocladius acrilobus n. sp. as
      male, female and pupa; Stictocladius fimbriatus n. sp. as male and female;
      Stictocladius fovigus n. sp. and Stictocladius nudiventer n. sp. as male and
      pupa; and Stictocladius privicalcar n. sp. and Stictocladius prostatus n. sp.
      each as male imago alone. The male and female of Stictocladius pulchripennis
      Edwards is redescribed and the pupa described. The male and female of
      Stictocladius flavozonatus Edwards and the male of Stictocladius calonotum
      Edwards are described. Five pupal types are described: Stictocladius sp. A (near
      S. acrilobus), Stictocladius sp. B (possibly S. calonotum), Stictocladius sp. C
      (near S. calonotum), Stictocladius sp. D (possibly S. flavozonatus) and
      Stictocladius sp. E with uncertain affinity. A larva from Chile of the
      Stictocladius 'sofour type' (Stictocladius sp. F) and an unreared larva from
      North America (Stictocladius sp. G) possibly belonging to S. acutus are
      described. Keys to named Neotropical male and female imagines of Stictocladius
      and to all pupal forms of Neotropical Stictocladius are provided. Some data
      concerning fourth instars of Stictocladius are presented. Means of
      differentiation from putative sister taxon Lopescladius are discussed.

PMID- 23950027
TI  - Description of the immature stages of four species of Macrodactylini (Coleoptera:
      Melolonthidae: Melolonthinae).
AB  - The third instar of the genera Ceraspis, Clavipalpus, Isonychus and Manopus
      (Melolonthidae: Melolonthinae: Macrodactylini) are described for the first time.
      Descriptions are based on the larvae of Ceraspis innotata (Blanchard),
      Clavipalpus ursinus Blanchard, Isonychus maculatus Waterhouse and Manopus
      biguttatus Laporte. The pupae of C. ursinus, I. maculatus and M. biguttatus are
      also described. A key to the larvae of nine genera of Macrodactylini and a list
      of the species with immature descriptions are provided.

PMID- 23950028
TI  - On the genus Chinavia orian: additions to the descriptions of three species
      (Hemiptera: Pentatomidae).
AB  - Chinavia Orian has 79 nominal species, 32 of them occur in Brazil, and
      intraspecific chromatic or morphological variations are known for both immatures
      and adults of some species. Additions to the descriptions of Chinavia difficilis
      (Stal), Chinavia geniculata (Dallas), and Chinavia obstinata (Stal) are provided
      in here, and corrections are proposed for the pictorial key by Schwertner &
      Grazia for the Brazilian species of Chinavia. New distribution records are also
      given for the first two species.

PMID- 23950029
TI  - New records of Rhyparochromidae (Hemiptera: Heteroptera: Lygaeoidea) from
      Colombia.
AB  - Five species in the tribes Lethaeini, Cistalia neotropicalis Slater & Baranowski
      and Paragonatas divergens Distant, and Ozophorini, Balboa variabilis Distant,
      Lygofuscanellus ozophoroides Slater, and Pamozophora englemani Ashlock & Slater,
      are recorded for the first time from Colombia. They are also the first generic
      record for this country. Photographs of all five species are included.

PMID- 23950030
TI  - Ibuprofen-loaded poly(trimethylene carbonate-co-epsilon-caprolactone) electrospun
      fibres for nerve regeneration.
AB  - The development of scaffolds that combine the delivery of drugs with the physical
      support provided by electrospun fibres holds great potential in the field of
      nerve regeneration. Here it is proposed the incorporation of ibuprofen, a well
      known non-steroidal anti-inflammatory drug, in electrospun fibres of the
      statistical copolymer poly(trimethylene carbonate-co-epsilon-caprolactone) [P(TMC
      CL)] to serve as a drug delivery system to enhance axonal regeneration in the
      context of a spinal cord lesion, by limiting the inflammatory response. P(TMC-CL)
      fibres were electrospun from mixtures of dichloromethane (DCM) and
      dimethylformamide (DMF). The solvent mixture applied influenced fibre morphology,
      as well as mean fibre diameter, which decreased as the DMF content in solution
      increased. Ibuprofen-loaded fibres were prepared from P(TMC-CL) solutions
      containing 5% ibuprofen (w/w of polymer). Increasing drug content to 10% led to
      jet instability, resulting in the formation of a less homogeneous fibrous mesh.
      Under the optimized conditions, drug-loading efficiency was above 80%. Confocal
      Raman mapping showed no preferential distribution of ibuprofen in P(TMC-CL)
      fibres. Under physiological conditions ibuprofen was released in 24 h. The
      release process being diffusion-dependent for fibres prepared from DCM solutions,
      in contrast to fibres prepared from DCM-DMF mixtures where burst release
      occurred. The biological activity of the drug released was demonstrated using
      human-derived macrophages. The release of prostaglandin E2 to the cell culture
      medium was reduced when cells were incubated with ibuprofen-loaded P(TMC-CL)
      fibres, confirming the biological significance of the drug delivery strategy
      presented. Overall, this study constitutes an important contribution to the
      design of a P(TMC-CL)-based nerve conduit with anti-inflammatory properties.

PMID- 23950032
TI  - Identification of radiation-induced radical structure in azocalix[4]arene: an EPR
      study.
AB  - A macrocyclic azocalix[4]arene (1) based ester derivative was synthesized. The
      single crystals of azocalix[4]arene were produced by slow evaporation of
      concentrated ethyl acetate solutions. These single crystals were exposed to (60)
      Co gamma rays with a dose rate of 0.980 kGy h(-1) for 48 and 72 h to produce a
      stable free radical. Electron paramagnetic resonance (EPR) measurements were
      performed in three mutually perpendicular planes of the single crystal in the
      magnetic field, in addition, temperature dependence of the EPR signal was studied
      between 120 K and 450 K. The spectra were found to be temperature and angular
      dependent. Analysis based on the spectra recorded showed that a free radical was
      formed by fission of a C-H bond. This radical is described as (*) Ca HCb H3 The
      averages of the principal values of the hyperfine parameters and g-factor are: g
      = 2.0034, AHa  = 1.28 mT, AH1=H2  = 1.00 mT, and AH3  = 0.49 mT.

PMID- 23950031
TI  - Bone marrow transplantation in Schimke immuno-osseous dysplasia.
AB  - Schimke immuno-osseous dysplasia (SIOD, OMIM 242900) is a rare autosomal
      recessive multisystem childhood disorder characterized by short stature, renal
      failure, T-cell immunodeficiency, and hypersensitivity to genotoxic agents. SIOD
      is associated with biallelic mutations in SMARCAL1 (SWI/SNF-related matrix
      associated actin-dependent regulator of chromatin, subfamily a-like 1), which
      encodes a DNA stress response enzyme with annealing helicase activity. Two
      features of SIOD causing much morbidity and mortality are bone marrow failure and
      T-cell deficiency with the consequent opportunistic infections. To address the
      safety and efficacy of bone marrow transplantation (BMT) in SIOD, we reviewed the
      outcomes of the only five SIOD patients known to us in whom bone marrow or
      hematopoietic stem cell transplantation has been attempted. We find that only one
      patient survived the transplantation procedure and that the existing indicators
      of a good prognosis for bone marrow transplantation were not predictive in this
      small cohort. Given these observations, we also discuss some considerations for
      the poor outcomes.

PMID- 23950033
TI  - Carbon-nanotube-modified electrodes for highly efficient acute neural recording.
AB  - Microelectrodes are widely used for monitoring neural activities in various
      neurobiological studies. The size of the neural electrode is an important factor
      in determining the signal-to-noise ratio (SNR) of recorded neural signals and,
      thereby, the recording sensitivity. Here, it is demonstrated that commercial
      tungsten microelectrodes can be modified with carbon nanotubes (CNTs), resulting
      in a highly sensitive recording ability. The impedance with the respect to
      surface area of the CNT-modified electrodes (CNEs) is much less than that of
      tungsten microelectrodes because of their large electrochemical surface area
      (ESA). In addition, the noise level of neural signals recorded by CNEs is
      significantly less. Thus, the SNR is greater than that obtained using tungsten
      microelectrodes. Importantly, when applied in a mouse brain in vivo, the CNEs can
      detect action potentials five times more efficiently than tungsten
      microelectrodes. This technique provides a significant advance in the recording
      of neural signals, especially in brain regions with sparse neuronal densities. 

PMID- 23950034
TI  - The progressive reduction in the ovarian reserve in young women after anticancer
      treatment.
AB  - Anticancer treatment can disturb gonadal function and deplete the primordial
      follicle pool, leading to premature menopause. We made a prospective analysis of
      serum hormone levels in young female cancer survivors who had been treated during
      childhood and adolescence. Serum anti-Mullerian hormone (AMH) as a marker of
      ovarian reserve, FSH, LH, and estradiol were measured in 33 women treated
      previously (6-11 years earlier) for Hodgkin Lymphoma, solid tumours, and after
      bone marrow transplantation, and in 34 healthy controls. The group of survivors
      was divided according to the risk of gonadotoxicity into the low risk and median
      risk group (LR+MR), and into the high risk (HR) group. The measurements were
      repeated after 5 years. In the HR group, AMH levels were significantly lower than
      in controls (p=0.001) and in the LR+MR group (p=0.006) at the time of the first
      examination fell progressively after 5 years (p=0.03), whereas elevated FSH
      values (p=0.053) increased (p=0.001). Unchanged LH values in the first
      measurement rose in the second one (p=0.001). In the LR+MR group, the levels of
      AMH and FSH were normal (compared to the control) at baseline, but after 5 years
      serum AMH decreased (p=0.027) and FSH increased (p=0.008). Our findings indicate
      that anticancer treatment during childhood and adolescence is associated with a
      serious, progressive risk of ovarian failure. It is necessary to inform female
      cancer survivors, especially the high risk patients, about the risk of premature
      menopause. 

PMID- 23950035
TI  - Enhanced immunoreceptor tyrosine-based activation motif signaling is related to
      pathological bone resorption during critical illness.
AB  - Prolonged critically ill patients present with distinct alterations in calcium
      and bone metabolism. Circulating bone formation markers are reduced and bone
      resorption markers are substantially elevated, indicating an uncoupling between
      osteoclast and osteoblast activity, possibly resulting in pronounced bone loss,
      impaired traumatic or surgical fracture healing, and osteoporosis. In addition,
      we have previously shown that increased circulating osteoclast precursors in
      critically ill patients result in increased osteoclastogenesis in vitro, possibly
      through FcgammaRIII signaling. In the current study, we investigated the effects
      of sustained critical illness on bone metabolism at the tissue level in a
      standardized rabbit model of prolonged (7 days), burn injury-induced critical
      illness. This in vivo model showed a reduction in serum ionized calcium and
      osteocalcin levels, as is seen in humans. Trabecular area, bone mineral content,
      and -density were decreased in sick rabbits [by 43% (p<0.01), 31% (p<0.01), and
      29% (p<0.05), respectively], as was the trabecular gene expression of osteoblast
      and angiogenesis markers, indicating decreased bone formation and impaired
      vascularization. There was no change in the expression of osteoclast
      differentiation markers from the canonical RANK/RANKL/OPG pathway, however, there
      was an increase in expression of markers from the non-canonical, immunoreceptor
      tyrosine-based activation motif (ITAM) signaling pathway, FcgammaRIII, and DAP12
      (148% and 59%, respectively; p<0.01). The current study has shown a detrimental
      effect of prolonged critical illness on trabecular bone integrity, possibly
      explained by reduced osteoblast differentiation and angiogenesis, coupled with
      increased osteoclastogenesis signaling that may be mediated via the non-canonical
      immunoreceptor tyrosine-based activation motif signaling pathway. 

PMID- 23950036
TI  - The brain: a new organ for the metabolic actions of SIRT1.
AB  - The sirtuins are a family of highly conserved nicotine adenine dinucleotide
      (NAD+)-dependent deacetylases that act as cellular sensors to detect energy
      availability and regulate metabolic processes. Sirtuin 1 (SIRT1) is one of the
      family members that is activated in response to caloric restriction, acting on
      multiple targets in a wide range of tissues. Recent studies have shown that SIRT1
      controls glucose and lipid metabolism in both liver and muscle, promotes fat
      mobilization, stimulates remodeling of white to brown fat, controls insulin
      secretion in the pancreas, and senses nutrient availability in the hypothalamus.
      SIRT1 is located in several areas of the brain and its central metabolic actions
      have attracted much attention in the last decade. In this short review, we
      summarize the main actions and molecular pathways triggered by SIRT1 that control
      feeding behavior, energy expenditure, glucose metabolism, and insulin
      sensitivity, with an emphasis on the emerging role of SIRT1 in the brain. 

PMID- 23950037
TI  - The role of obestatin in glucose and lipid metabolism.
AB  - Obestatin is a 23 amino acid peptide encoded by the ghrelin gene, which, like
      ghrelin, is mainly produced by the stomach, as well as by a wide range of other
      tissues. Obestatin remains a controversial peptide, as the initial finding of its
      binding to the orphan receptor GPR39 and the inhibitory effect on food intake has
      been questioned. In fact, to date, its biological effects are still largely
      unknown, although it is becoming clear that obestatin is a pleiotropic hormone,
      exerting a variety of effects in different cell types and tissues. Indeed,
      besides regulating cell proliferation and survival, obestatin has been shown to
      regulate glucose and lipid metabolism, both in vitro, in pancreatic beta-cells
      and adipocytes, and in vivo in rodents. Furthermore, its positive effects on
      glucose homeostasis, combined with the anti-inflammatory actions, make this
      peptide appealing as a candidate for treating metabolic disorders such as insulin
      resistance and diabetes. 

PMID- 23950038
TI  - Hypothalamic actions of apelin on energy metabolism: new insight on glucose
      homeostasis and metabolic disorders.
AB  - Hypothalamus is key area implicated in control of glucose homeostasis. This
      structure integrates nervous and peripheral informations to adapt a response
      modifying peripheral glucose utilization and maintaining energetic balance. Among
      peripheral signals, adipokines such as adiponectin and leptin are of special
      importance since deregulations of their actions are closely associated to
      metabolic disorders such as obesity and type 2 diabetes. During the past ten
      years, we have identified a new adipokine named apelin which has emerging role in
      the control of metabolism. The originality of the apelinergic system is to be
      largely represented in peripheral tissues (adipose tissue, intestine, etc.) and
      in the brain. Then, apelin is released by adipose tissue as all adipokines, but
      also present another crucial role as neurotransmitter in hypothalamic neurons. By
      acting in the whole body, apelin exerts pleiotropic actions and is now considered
      as a major determinant of physiological functions. Besides its general beneficial
      effects on peripheral targets, central action of apelin remains still a matter of
      debate. In this review, we have made a parallel between peripheral vs. central
      actions of apelin in term of signalization and effects. Then, we have focused our
      attention on hypothalamic apelin and its potential role in glucose metabolism and
      associated pathologies. 

PMID- 23950039
TI  - Neonatal murine skin-derived cells transplanted using a mini-chamber model
      produce robust and normal hair.
AB  - Hair follicle reconstitution models are useful tools for investigating signalling
      and cytokines during hair follicle morphogenesis and cycling. The chamber model
      is one of the most established methods available for the study of hair follicle
      reconstitution and appears to be the most reproducible. However, the chamber
      model has several deficiencies: infection of skin wounds and subsequent animal
      death commonly occur, a large number of cells are required and only one chamber
      can be transplanted onto each animal. We modified these deficiencies by using a
      mini-chamber method, which has the advantages of having a high graft take rate,
      requiring fewer cells and allowing several mini-chambers to be transplanted onto
      each animal. In our study, cultured dermal cells at different passages (0 to
      high) lost the ability to reconstruct hair follicles, but dermal cells cultured
      overnight (12 h) retained this ability. Using the assay, newborn mice dermal
      cells that were freshly isolated and cultured overnight (12 h), as well as
      cultured dermal papilla cells from mice vibrissa follicles, all reconstructed
      hair follicles. However, cultured dermal papilla cells from human scalp follicles
      could not reconstruct hair follicles. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 23950040
TI  - Color and shape discrimination in the stingless bee Scaptotrigona mexicana Guerin
      (Hymenoptera, Apidae).
AB  - To increase our understanding in bee vision ecology, we investigated the color
      and shape discrimination performance of the stingless bee Scaptotrigona mexicana
      Guerin. Our main goal was to describe the choice behavior of experienced foragers
      over time, trying to understand to what extent color and shape stimuli
      (separately tested) aid them to choose the rewarding option, in the presence of
      distracting, unrewarding stimuli. Single foragers were trained to collect sucrose
      solution from a target plate. Afterwards, one distracting, unrewarding plate was
      placed besides the target plate and eight choices were recorded. Our results
      showed that both color and shape stimuli assisted efficiently the trained
      foragers in locating the target plate. However, foragers chose significantly more
      often the target plate in the color experiments than in the shape experiments. In
      conclusion, in our experimental setup, color was of better assistance to the
      foragers of S. mexicana than shape to choose their rewards. This is the first
      study in which it is demonstrated that the choice performance over time in a
      stingless bee depends upon the characteristics of the resource, such as shape and
      color. 

PMID- 23950041
TI  - Fluctuating asymmetry and wing size of Argia tinctipennis Selys (Zygoptera:
      Coenagrionidae) in relation to riparian forest preservation status.
AB  - Effects of riparian vegetation removal on body size and wing fluctuating
      asymmetry (FA) of Argia tinctipennis Selys (Odonata: Coenagrionidae) were studied
      in the River Suia-Micu basin, which is part of the Xingu basin in Brazilian
      Amazonia. A total of 70 specimens (n = 33 from preserved and n = 37 from degraded
      areas) was measured. Five wing measures of each wing (totalizing ten measured
      characters) were taken. Preserved and degraded points presented non-overlapped
      variations of a Habitat Integrity Index, supporting the environmental
      differentiation between these two categories. FA increases in degraded areas
      approximately four times for the width between the nodus and proximal portion of
      the pterostigma of forewings (FW), two times for the width of the wing in the
      region of nodus of FW, and approximately 1.7 times for the number of postnodal
      cells of FW. The increase is almost five times for the width between the nodus
      and the proximal portion of the pterostigma of hind wings (HW), three times for
      the number of postnodal cells of HW, and approximately 1.6 times the width
      between quadrangle and nodus of HW. Individuals of preserved sites were nearly
      3.3% larger than for degraded sites, based on mean hind wing length. Our results
      supports that the development of A. tinctipennis in degraded areas is affected by
      riparian vegetation removal and may reflect in wing FA variations. Consequently,
      these FA measures may be a useful tool for bioassessment using Odonata insects as
      a model.

PMID- 23950042
TI  - The presence-absence situation and its impact on the assemblage structure and
      interspecific relations of Pronophilina butterflies in the Venezuelan Andes
      (Lepidoptera: Nymphalidae).
AB  - Assemblage structure and altitudinal patterns of Pronophilina, a species-rich
      group of Andean butterflies, are compared in El Baho and Monte Zerpa, two closely
      situated and ecologically similar Andean localities. Their faunas differ only by
      the absence of Pedaliodes ornata Grose-Smith in El Baho. There are, however,
      important structural differences between the two Pronophilina assemblages.
      Whereas there are five co-dominant species in Monte Zerpa, including P. ornata,
      Pedaliodes minabilis Pyrcz is the only dominant with more than half of all the
      individuals in the sample in El Baho. The absence of P. ornata in El Baho is
      investigated from historical, geographic, and ecological perspectives exploring
      the factors responsible for its possible extinction including climate change,
      mass dying out of host plants, and competitive exclusion. Although competitive
      exclusion between P. ornata and P. minabilis is a plausible mechanism, considered
      that their ecological niches overlap, which suggests a limiting influence on each
      other's populations, the object of competition was not identified, and the reason
      of the absence of P. ornata in El Baho could not be established. The role of
      spatial interference related to imperfect sexual behavioral isolation is
      evaluated in maintaining the parapatric altitudinal distributions of three pairs
      of phenotypically similar and related species of Pedaliodes, Corades, and
      Lymanopoda. 

PMID- 23950043
TI  - Exploration of substrate vibrations as communication signals in a webspinner from
      Ecuador (Embioptera: Clothodidae).
AB  - Embiopterans are among the least known of all insect orders, and yet their
      behavior is worthy of investigation for many reasons. They spin silk produced in
      glands in their front tarsi and live in groups, usually mothers with their young
      and sometimes in large colonies with many reproductive females sharing the silk.
      We discovered a large embiid (Clothodidae) in an Ecuadorian rain forest living
      under camouflaged silk sheets spun onto the bark of trees. Observations in
      previous studies of a related Trinidadian clothodid revealed that individuals
      shake and lunge their bodies in response to intruders of their silk domicile. We
      took the opportunity afforded by the discovery of the large clothodids to rear
      them in the laboratory and to investigate their communication behavior. We used
      piezoelectric film to detect substrate vibrations generated by adult females as
      elicited by a variety of intruders (an artificial stimulus, conspecific female or
      male, or a female of different species of webspinners). The residents produced
      three signals distinguishable by behavioral action, frequency (hertz), pulses per
      bout, and amplitude at peak frequency. We designated these as lift silk, shake,
      and snapback. Shakes varied the most in amplitude and frequency in response to
      the different intruders, and therefore, we propose that shakes may transmit the
      most information as individuals contact each other. This is the first report to
      characterize spectral qualities and contexts of substrate vibrations in an
      embiopteran. 

PMID- 23950044
TI  - Application of microsatellite primers developed for Polistes in the independent
      founding wasp Polists satan Bequaert (Hymenoptera: Vespidae).
AB  - Microsatellite primers developed for a given species are sometimes useful for
      another in the same genus and in other genera within the same family, making
      possible to search for pre-existing suitable primers in the databanks such as
      GenBank. We examined whether existing primers developed for Polistes could be
      used for Polistes satan Bequaert. We tested 50 microsatellite primers from three
      Polistes species and found that six microsatellite loci show polymorphism in size
      in P. satan. These six loci were highly polymorphic, having four to 15 alleles in
      P. satan with an expected heterozygosity of 0.525-0.832. These loci can be used
      to study parameters concerning genetic relatedness such as social interactions in
      colonies and genetic conflicts of interest among nestmate individuals. 

PMID- 23950045
TI  - Aedeagal divergence in sympatric populations of two sibling species of
      cactophilic Drosophila (Diptera: Drosophilidae): evidence of character
      displacement?
AB  - Aedeagal morphology of two sibling cactophilic species, Drosophila buzzatii
      Patterson & Wheeler and Drosophila koepferae Fontdevila & Wasserman, was analyzed
      in nine allopatric and three sympatric locations throughout South America.
      Morphological differences were detected for both aedeagus size and shape between
      sympatric and allopatric populations of D. buzzatii, despite the significant
      variability within both groups. Populations of D. buzzatii sympatric with D.
      koepferae displayed smaller aedeagus than the allopatric ones as well as more
      differentiated aedeagus shape. The shape differences were non-allometric and
      mainly consisted in a change of curvature of the dorsal margin of the aedeagus
      being more pronounced in males from populations sympatric with D. koepferae. It
      is concluded that aedeagal morphology presented some degree of character
      displacement in both size and shape in populations of D. buzzatii in sympatry
      with D. koepferae. These results might suggest the existence of mechanisms of
      interspecific recognition and hybridization prevention between these species that
      include the morphology of the male genitalia. 

PMID- 23950046
TI  - The Tannea Blackwelder species of Ecuador with description of new species
      (Coleoptera: Staphylinidae: Osoriinae).
AB  - Two new species of the genus Tannea Blackwelder from Ecuador, Tannea hermani n.
      sp. and Tannea bellavistae n. sp. are herein described, and a complete list of
      records of all Tannea species found in Ecuador is provided together with a key to
      the species. Additionally, the geographic distribution of the Tannea species of
      Ecuador and their altitudinal distribution are discussed. 

PMID- 23950047
TI  - Insecticidal activity of the granulosis virus in combination with neem products
      and talc powder against the potato tuberworm Phthorimaea operculella (Zeller)
      (Lepidoptera: Gelechiidae).
AB  - The potato tuberworm Phthorimaea operculella (Zeller) is an important
      agricultural pest that causes significant economic losses to potato growers
      worldwide. The addition of an effective method of biological control for the
      potato tuberworm is greatly needed, and is currently unavailable in Brazil. The
      granulosis virus (Baculoviridae) is a promising biological control agent to
      protect post-harvest potatoes and in storage from the potato tuberworm. However,
      the control measure must be economically feasible. Liquid suspensions of a
      granulosis virus applied alone or in mixture with two commercial neem oil-based
      products (DalNeemTM and NeemAzalTM), and a dry powder formulation of viral
      granules were evaluated for control of potato tuberworm larvae by treating potato
      tubers under laboratory conditions. High larval mortality (86.7%) was achieved
      when DalNeem and virus were applied together at 4 mg of azadirachtin/L and 10(4)
      occlusion bodies (OBs)/mL, respectively. This combination resulted in >=50%
      efficacy in relation to their counterparts alone. Conversely, NeemAzal did not
      enhance virus effectiveness against larvae of the potato tuberworm. The talc
      based virus formulation was used for dusting seed tubers at different
      concentrations and resulted in 100% larval mortality at 5 * 10(8) OBs/g.
      Formulated and unformulated virus provided 50% mortality at 166 OBs/g and at 5.0
      * 10(5) OBs/mL, respectively. As a result, talc-based virus formulation had a
      better control efficiency on potato tuberworm than the aqueous virus suspension.
      The granulosis virus combined with DalNeem at low rates or formulated with talc
      powder is a viable option to control the potato tuberworm under storage
      conditions.

PMID- 23950048
TI  - Increasing attractiveness of baits with venom gland extract for Atta sexdens
      rubropilosa (Forel) (Hymenoptera: Formicidae).
AB  - The effect of larval cuticle extract (larval pheromone) and venom gland extract
      (trail pheromone) on transport of formulated baits by Atta sexdens rubropilosa
      (Forel) was studied in the field and under laboratory conditions. In the
      laboratory, we observed the transport to the nest of baits impregnated with 10
      MUL of venom gland extract (0.01 gland/bait) or 10 MUL of larval cuticle extract
      (0.05 larva/bait). The most transported impregnated bait was then tested in the
      field placing rubber septa impregnated with 100 mL of extract or with 100 mL of
      solvent with the baits at 0.2, 1.0, 5.0, and 10.0 m away from the trail and from
      the nest entrance. Baits impregnated with venom gland extract were transported
      more often than baits formulated with larval cuticle extract. In field tests, the
      venom gland extract reduced the time required for ants to detect baits and
      increased the transport of baits displayed at 0.2 m from the foraging trail or
      nest entrance. The increase in the transport of impregnated baits and the lower
      time to be transported might help to reduce the loss of bait in the field and
      decrease the risk of active ingredient contacts with non-target species.

PMID- 23950049
TI  - Synanthropy of Calliphoridae and Sarcophagidae (Diptera) in Bogota, Colombia.
AB  - Calliphoridae and Sarcophagidae have medical and forensic importance. Species of
      these families are the first insects colonizing corpses and are, therefore,
      useful in establishing postmortem interval and as indicators in corpse transfer.
      The synanthropic index (SI) measures the relation of dipteran species with human
      settlements. Our main objective was to determine the synanthropic index of these
      families during the rainy and dry seasons in Bogota. Captures were carried out
      using traps with baits (beef liver) in three zones (urban, rural, and forest
      areas). In the family Calliphoridae, the most abundant species were Calliphora
      vicina (Robineau-Desvoidy) with a sinanthropy index (SI) of +83.1, followed by
      Lucilia sericata (Meigen) (SI = +92.2) and Compsomyiops verena (Walker) (SI =
      +42.0). Calliphora nigribasis (Macquart) was not associated with human
      settlements, while Sarconesiopsis magellanica (Le Guillou) was present in the
      three zones and considered hemisynanthropic (SI = +19.0). Roraimomusca roraima
      (Townsend) was reported for the first time in Bogota and was a non-synanthropic
      species (SI = -36.0). On the other hand, in Sarcophagidae, three species were
      collected: Ravinia rufipes (Twonsend), Ravinia colombiana (Lopes), and
      Boettcheria sp1, which were abundant in the rural and forest zones, the first
      having a dual characterization as synanthropic and hemisynanthropic, while the
      other two were hemisynanthropic. Our data showed differences in the association
      of Calliphoridae species with the three environments, whereas Sarcophagidae were
      distributed in locations with a lower human impact.

PMID- 23950050
TI  - Diversity and synanthropy of Calliphoridae (Diptera) in the region of Rio Claro,
      SP, Brazil.
AB  - Dipteran blowflies (Calliphoridae) are of great medical and hygienic importance
      as vectors of pathogens and as parasites of living and dead tissue, and their
      association with carrion allows their use in forensic entomology. The objective
      of this study was to determine the synanthropic index of adult Calliphoridae
      (Diptera) collected in Rio Claro, Sao Paulo. Sampling occurred between September
      2009 and August 2010. Traps baited with sardines, beef liver, and minced meat
      were assessed for five consecutive days per month in three distinct ecological
      areas representing urban, rural, and forest environments. The most abundant
      species was Lucilia eximia (Wiedemann), followed by Chrysomya albiceps
      (Wiedemann) and Chrysomya megacephala (Fabricius). Lucilia eximia was the only
      species present in all seasons and the only species collected during the winter.
      The season with the lowest abundance was winter, with 69 (5.5%) specimens, and
      spring was the season with the greatest number of specimens collected (774
      61.8%). The only species found outside inhabited areas (synanthropic) was Lucilia
      cuprina (Wiedemann), with a synanthropy index (SI) value of +5.7. The SI values
      for the other species were negative, showing a preference for uninhabited areas.
      The rural and urban areas were most similar in terms of species composition as
      were the beef and sardine baits. Among the baits used, liver attracted the
      greatest abundance of calliphorids, whereas minced meat attracted the greatest
      diversity. 

PMID- 23950051
TI  - Use of Dactylopius coccus Costa (Hemiptera: Coccoidea) pigments in the detection
      of larvae and pupae of Plutella xylostella (L.) (Lepidoptera: Yponomeutidae).
AB  - Carmines obtained from the dye of Dactylopius coccus Costa (Hemiptera: Coccoidea)
      were used for the detection of larvae and pupae of Plutella xylostella (L.)
      (Lepidoptera: Yponomeutidae) in broccoli inflorescences. Larvae were dyed with
      carmine II and red cochineal, while the majority of the dyes, with the exception
      of carmine III and the aqueous extract, were suitable to dye pupae. In the
      broccoli lumps exposed to the dyes, only the verge of the stems were actually
      dyed, right in the position where the incision took place, an appropriate
      characteristic for implementing this technique for commercial use. 

PMID- 23950052
TI  - First record of Teratopactus nodicollis (Coleoptera: Curculionidae) in dry bean
      (Phaseolus vulgaris).
AB  - Observations on the bioecology and damage of Teratopactus nodicollis Boheman on
      Phaseolus vulgaris were carried out on field samples by assessing the number of
      larvae and root damage in 40 ha of a dry bean field from the Federal District,
      Brazil (16 degrees 4'28.41"W; 47 degrees 30'21.13"S). Larvae caused the greatest
      damage at the stage of germination, emergence, and primary leaves, producing 50 %
      stand reduction. Most larvae pupated in August and September, and adult emergence
      occurred in middle October. Some larvae were infected with the fungus Metarhizium
      spp., a biological agent that would be naturally controlling this insect.

PMID- 23950053
TI  - Operclipygus hospes (Lewis) (Coleoptera, Histeridae): a beetle of potential
      forensic importance for buried bodies.
AB  - Operclipygus hospes (Lewis) is reported as a new record of Histeridae associated
      with buried bodies in the Neotropical region. It is also suggested that O. hospes
      has an important role in forensic entomology as a seasonal indicator. To assist
      in the recognition and the use of this species in forensic entomology, diagnosis
      and illustrations of the main characters of the genus and species are provided. 

PMID- 23950054
TI  - Prenatal presentation and postnatal evolution of a patient with Jansen
      metaphyseal dysplasia with a novel missense mutation in PTH1R.
AB  - Wave-shaped ribs were detected at prenatal ultrasound in a 20(+1) week female
      fetus. At birth, skeletal radiographs showed marked hypomineralization and
      suggested hypophosphatasia. However, elevated blood calcium and alkaline
      phosphatase excluded hypophosphatasia and raised the possibility of Jansen
      metaphyseal dysplasia. Molecular analysis of the PTH/PTHrP receptor gene (PTH1R)
      showed heterozygosity for a previously undescribed transversion variant
      (c.1373T>A), which predicts p.Ile458Lys. In vitro evaluation of wild type and
      mutant PTH/PTHrP receptors supported the pathogenic role of the p.Ile458Lys
      substitution, and confirmed the diagnosis of Jansen metaphyseal dysplasia. This
      disorder may present prenatally with wavy ribs and in the newborn with
      hypomineralization, and may therefore be confused with hypophosphatasia. The
      mottled metaphyseal lesions typically associated with this disease appear only in
      childhood.

PMID- 23950055
TI  - Reflecting on the efficacy of cognitive mapping for decision-making in
      intellectual disability care: a case study.
AB  - The central aspect of this study is a set of reflections on the efficacy of soft
      operational research techniques in understanding the dynamics of a complex system
      such as intellectual disability (ID) care providers. Organizations providing
      services to ID patients are complex and have many interacting stakeholders with
      often different and competing interests. Understanding the causes for failures in
      complex systems is crucial for appreciating the multiple perspectives of the key
      stakeholders of the system. Knowing the factors that adversely affect delivery of
      a patient-centred care by ID provider organizations offers the potential for
      identifying more effective resource-allocation solutions. The authors suggest
      cognitive mapping as a starting point for system dynamics modelling of optimal
      resource-allocation projects in ID care. The application of the method is
      illustrated via a case study in one of the ID care providers in the Netherlands.
      The paper discusses some of the practical implications of applying problem
      structuring methods that support gathering feedback from vulnerable service users
      and front-line workers. The authors concluded that cognitive mapping technique
      can assist the management of healthcare organizations in strategic decision
      making.

PMID- 23950057
TI  - Oxytocin influences avoidant reactions to social threat in adults with borderline
      personality disorder.
AB  - BACKGROUND: Borderline personality disorder (BPD) is characterized by
      interpersonal dysfunction, emotional instability, impulsivity, and risk-taking
      behavior. Recent research has focused on the role of oxytocin in BPD, with mixed
      results as regards the processing of social stimuli. METHODS: In a double-blind
      randomized placebo-controlled study, 13 BPD patients and 13 controls performed a
      dot probe task to examine attentional biases to happy and angry faces after
      intranasal application of oxytocin or placebo. Childhood trauma was examined
      using the childhood trauma questionnaire. RESULTS: In the placebo condition,
      patients with BPD (but not controls) showed an avoidant reaction to angry faces
      (but not happy faces). The strength of the avoidant reaction correlated with the
      severity of childhood trauma. This behavioral response (as well as the
      correlation) was abolished in the oxytocin condition. CONCLUSIONS: Adult patients
      with BPD show an avoidant response to social threat, a reaction that is linked
      with traumatic experiences during childhood. This response pattern is altered by
      oxytocin, possibly by reducing stress and inhibiting social withdrawal from
      distressing social stimuli.

PMID- 23950056
TI  - A nontoxic additive to introduce x-ray contrast into poly(lactic acid).
      Implications for transient medical implants such as bioresorbable coronary
      vascular scaffolds.
AB  - Bioresorbable coronary vascular scaffolds are about to revolutionize the
      landscape of interventional cardiology. These scaffolds, consisting of a poly(L
      lactic acid) interior and a poly(D,L-lactic acid) surface coating, offer a
      genuine alternative for metallic coronary stents. Perhaps the only remaining
      drawback is that monitoring during implantation is limited to two X-ray contrast
      points. Here, a new approach to make the biodegradable scaffolds entirely
      radiopaque is explored. A new contrast agent is designed and synthesized. This
      compound is miscible with poly(D,L-lactic acid) matrix, and nontoxic to multiple
      cell types. Blends of poly(D,L-lactic acid) and the contrast agent are found to
      be hemocompatible, noncytotoxic, and radiopaque. The data show that it is
      possible to manufacture fully radiopaque bioresorbable coronary vascular
      scaffolds. Whole-stent X-ray visibility helps interventionalists ensure that the
      scaffold deploys completely. This important advantage may translate into improved
      safety, accuracy, and clinical performance of cardiac stents.

PMID- 23950058
TI  - Differentiated adipose-derived stem cells act synergistically with RGD-modified
      surfaces to improve neurite outgrowth in a co-culture model.
AB  - Peripheral nerve damage is a problem encountered after trauma and during surgery
      and the development of synthetic polymer conduits may offer a promising
      alternative to autografts. In order to improve the performance of the polymer to
      be used for nerve conduits, poly-epsilon-caprolactone (PCL) films were chemically
      functionalized with RGD moieties, using a chemical reaction previously developed.
      In vitro cultures of dissociated dorsal root ganglion (DRG) neurons provide a
      valid model to study different factors affecting axonal growth. In this work, DRG
      neurons were cultured on RGD-functionalized PCL films. Adult adipose-derived stem
      cells differentiated to Schwann cells (dASCs) were initially cultured on the
      functionalized PCL films, resulting in improved attachment and proliferation.
      dASCs were also co-cultured with DRG neurons on treated and untreated PCL to
      assess stimulation by dASCs on neurite outgrowth. Neuron response was generally
      poor on untreated PCL films, but long neurites were observed in the presence of
      dASCs or RGD moieties. A combination of the two factors enhanced even further
      neurite outgrowth, acting synergistically. Finally, in order to better understand
      the extracellular matrix (ECM)-cell interaction, a beta1 integrin blocking
      experiment was carried out. Neurite outgrowth was not affected by the specific
      antibody blocking, showing that beta1 integrin function can be compensated by
      other molecules present on the cell membrane. Copyright (c) 2013 John Wiley &
      Sons, Ltd.

PMID- 23950059
TI  - Spatial distribution and fruiting phenology of Protium heptaphyllum (Burseraceae)
      determine the design of the underground foraging system of Atta sexdens L.
      (Hymenoptera: Formicidae).
AB  - Leaf-cutting ants have long been recognized to forage via complex trail systems
      but the nature and the ecological drivers of the different foraging strategies
      adopted remain a key topic. Here, we described the spatiotemporal use of
      belowground foraging galleries by Atta sexdens L. in the Brazilian Atlantic
      forest, and examined the adaptive advantages of this foraging strategy. Protium
      heptaphyllum adult trees (DBH > 10 cm), seed/seedling clumps and ant gallery
      entrances were mapped across two 1-ha plots during two consecutive fruiting
      seasons (2002 and 2004). We recorded 75 ca. 40 cm deep gallery entrances beneath
      26 P. heptaphyllum trees at nest distances ranging from 14 to 57 m. Furthermore,
      gallery abundance and galleries associated with seed/seedling clumps correlated
      positively with P. heptaphyllum density. Our results indicate that A. sexdens was
      able to set a permanent system of underground galleries targeting P. heptaphyllum
      trees and their seeds on the ground. Such network of galleries was spatially
      arranged according to both the spatial distribution and abundance of P.
      heptaphyllum trees in a way that most gallery entrances were disposed beneath or
      in close periphery of P. heptaphyllum crowns. Our findings suggest that
      underground trail systems shaped by fruit resources represent a foraging strategy
      clearly more common than existing literature on the subject would suggest. In
      addition, it reinforces the notion that the spatiotemporal availability of
      resources combined with predation risk largely influence trail configurations as
      well as overall foraging strategies adopted by leaf-cutting ants.

PMID- 23950060
TI  - Myrmecofauna of ironstone outcrops: composition and diversity.
AB  - The Iron Quadrangle in the state of Minas Gerais, Brazil, harbors ironstone
      outcrops locally known as cangas, which are historically under great anthropic
      pressure. The functions performed by ants in environments with severe edapho
      climatic conditions, such as cangas, are poorly known. Considering the lack of
      studies and the potential role of ants in cangas, this study aimed to identify
      the taxonomic composition of the myrmecofauna that occurs in the soil of two
      campo rupestre areas (rupestral plant communities) on cangas under different
      anthropic impacts and evaluate the influence of seasonality and degree of
      degradation on the diversity and composition of the myrmecofauna. This is the
      first study to systematically investigate ant fauna collected with baits on
      ironstone outcrops. Sardine and honey baits were used in dry and rainy periods.
      Fourteen species distributed among ten genera belonging to five subfamilies were
      found. The total number of baits visited in the dry season was lower than in the
      rainy season. Both habitats had a reasonable similarity in their composition
      (Jaccard similarity index = 0.571). Multivariate analyses suggest a greater
      similarity between areas than seasons. The diversity of ants in the cangas is low
      compared to other Cerrado environments where more than 20 species are frequently
      collected in these types of study. This low richness may be related to the
      adverse conditions characteristic of ironstone outcrops. We hope our data will
      help to expand the actions to manage and preserve cangas in the Iron Quadrangle.

PMID- 23950061
TI  - Biotic and abiotic factors affecting Brevicoryne brassicae (L.) (Hemiptera:
      Aphididae) and the associated hyperparasitoid Alloxysta fuscicornis Hartig
      (Hymenoptera: Figitidae) morphologies.
AB  - This study investigates the influence of biotic and abiotic factors associated
      with the morphological development of Brevicoryne brassicae (Linnaeus) and the
      associated hyperparasitoid Alloxysta fuscicornis (Hartig). The experiment
      involved the examination of whether aphid size was influenced by their vertical
      distribution and density on the host plant, as well as whether variations in
      hyperparasitoid size and symmetry were correlated with those of their aphid
      hosts. An aphid multivariate size index was obtained using principal component
      analysis, while symmetry was evaluated in terms of fluctuating asymmetry (FA).
      Samples were collected in 2007 on cabbage plants cultivated at an experimental
      farm located in Uberlandia, Minas Gerais, Brazil (18 degrees 56'54"S; 48 degrees
      12'46"W). The results demonstrated that the size of B. brassicae was negatively
      associated with temperature, but not with its vertical distribution on the host
      plant. Temperature was also negatively correlated with hyperparasitoid size.
      During warmer periods, females produced large quantities of small-sized
      offspring, whereas an opposite pattern, i.e. the production of fewer offspring of
      larger size took place during colder periods. This type of adjustment involving
      trade-offs between physiological and morphological mechanisms, as well as
      individual interaction with abiotic environmental factors, such as temperature,
      can be considered an adaptive plastic response in order to increase the chances
      of survival at a given locality. The encountered relationship between aphid and
      hyperparasitoid sizes may be an after effect of their indirectly biotic
      interaction. Hyperparasitoid FA was dependent on the width of the mummified
      aphids. However, the hypothesis that temperature and vertical distribution on the
      host plant might influence FA was not confirmed.

PMID- 23950062
TI  - Morphology and volatile compounds of metathoracic scent gland in Tessaratoma
      papillosa (Drury) (Hemiptera: Tessaratomidae).
AB  - Tessaratoma papillosa (Drury) (Hemiptera: Tessaratomidae) is a serious insect
      pest of litchi and longan in South China. When disturbed, this insect could
      release large quantities of disagreeable odorous volatiles from its scent gland.
      Knowledge on the scent gland and its secretion is crucial for developing the
      semiochemical methods to manage this pest. Morphology and ultrastructure of the
      metathoracic scent glands (MTGs) were studied under stereo and scanning electron
      microscopy, and the volatile compounds of MTGs from both male and female T.
      papillosa were analyzed with coupled gas chromatography-mass spectrometry (GC
      MS). The MTG complex is located between the metathorax and the first abdominal
      segment at the ventral surface of the insect, which has a well-developed single
      double valve cystic-shaped orange median reservoir, paired colorless lateral
      glands in both sides, and a long and wavy tubular accessory gland that inlays
      tightly into the ventral edge around the median reservoir. The MTG opens to the
      body surface through paired ostioles located between the meso- and metacoxae of
      the evaporatorium with mushroom bodies. The GC-MS analyses showed that female and
      male adults have nine major volatile components in common. Tridecane is the most
      abundant in both females and males, reaching up to 47.1% and 51.8% of relative
      amount, respectively. The minor component is benzophenone with only 0.28% and
      0.14%. Furthermore, undecane, tetradecane, 3-methyl-tridecane, and
      cyclopentadecane were found only in males. The possible function of volatile
      compounds of MTG contents in T. papillosa is addressed. 

PMID- 23950063
TI  - Host location by ichneumonid parasitoids is associated with nest dimensions of
      the host bee species.
AB  - Parasitoid fitness depends on the ability of females to locate a host. In some
      species of Ichneumonoidea, female parasitoids detect potential hosts through
      vibratory cues emanating from them or through vibrational sounding produced by
      antennal tapping on the substrate. In this study, we (1) describe host location
      behaviors in Grotea gayi Spinola (Hymenoptera: Ichneumonidae) and Labena sp. on
      nests of Manuelia postica Spinola (Hymenoptera: Apidae), (2) compare nest
      dimensions between parasitized and unparasitized nests, (3) correlate the length
      of M. postica nests with the number of immature individuals developing, and (4)
      establish the relative proportion of parasitized nests along the breeding period
      of M. postica. Based on our results, we propose that these parasitoids use
      vibrational sounding as a host location mechanism and that they are able to
      assess host nest dimensions and choose those which may provide them with a higher
      fitness. Finally, we discuss an ancestral host-parasitoid relationship between
      Manuelia and ichneumonid species. 

PMID- 23950064
TI  - Performance of the wheat armyworm, Pseudaletia sequax Franclemont, on natural and
      artificial diets.
AB  - Armyworms in the genus Pseudaletia Franclemont are important pests of cereal
      crops worldwide. The development of pest management strategies is largely
      dependent on studies involving the relationship among the pest, its host plants
      and natural enemies, as well as its susceptibility to chemical and biological
      control strategies. Part of these studies requires rearing the species of
      interest under laboratory conditions, which can be greatly facilitated by the use
      of artificial diets. In the present study, the effects of three artificial diets
      on development, survival, reproduction and demographic parameters of P. sequax
      were compared to a natural host plant, Pennisetum clandestinum. A diet based on
      pinto beans, wheat germ and torula yeast provided the best results in comparison
      to those obtained with the host plant. The most important life history parameters
      used in the evaluation of the nutritional quality of the diets were fecundity,
      egg viability and pupae deformities. The intrinsic rate of increase and the net
      reproductive rate were higher when individuals were fed on the artificial diet if
      compared to the host plant, indicating the suitability of the tested diet for the
      rearing of P. sequax. This artificial diet has been used successfully for the
      rearing of P. sequax without any fitness effect for over 18 consecutive
      generations. 

PMID- 23950065
TI  - Spatial-temporal variation in orchid bee communities (Hymenoptera: Apidae) in
      remnants of arboreal Caatinga in the Chapada Diamantina region, state of Bahia,
      Brazil.
AB  - The spatial and temporal distribution of organisms is a fundamental aspect of
      biological communities. The present study focused on three remnants of arboreal
      Caatinga in northeastern Brazil between May, 2009 and April, 2010. A total of 627
      euglossine males were captured in traps baited with artificial aromatic
      compounds. The specimens belonged to 14 species and four genera: Euglossa
      Latreille, Eulaema Lepeletier, Eufriesea Cockerell, and Exaerete Hoffmannsegg.
      Eulaema nigrita Lepeletier (41.6), Euglossa carolina Nemesio (15.3%), Eulaema
      marcii Nemesio (13.6%), and Euglossa melanotricha Moure (12.8%) were the most
      common species sampled. The distribution of collected specimens per fragment was
      as follows: Brauna (280 ha)--259 individuals belonging to 14 species; Cambui (179
      ha)--161 individuals from eight species; and Pindoba (100 ha)--207 individuals
      represented by seven species. Brauna had the highest diversity (H' = 1.91) and
      estimated species richness. The largest fragment was the main source of the
      observed variation in species richness and abundance, indicating a non-random
      pattern of spatial distribution. The analysis of environmental factors indicated
      that seasonal variation in these factors was the principal determinant of species
      occurrence and abundance.

PMID- 23950066
TI  - Morphology of male reproductive systems in Ephemeroptera: intrinsic musculature.
AB  - Although the Ephemeroptera have been studied over a long period of time, there
      are still few studies on the morphology of male reproductive system. The
      spermatic ducts are considered conserved among different Ephemeroptera groups.
      However, previous studies distinguished different organizational patterns of the
      spermatic duct intrinsic musculature. This study describes the morphology of the
      spermatic ducts, especially their musculature, in six species of Ephemeroptera,
      representing five families. We have observed variations in the organizational
      pattern of the spermatic ducts, even between species from the same family.
      Moreover, all species studied had intrinsic musculature in the spermatic ducts
      although with different organizational patterns. Thus, we believe that this
      musculature is important to move the spermatozoa along the ducts of all
      Ephemeroptera and not only of those with aflagellated spermatozoa
      (Leptophlebiidae). The variations in musculature organization must be related to
      differences in reproductive physiology (i.e., copula duration) and not only with
      spermatozoa characteristics. 

PMID- 23950067
TI  - Morphological changes in the midgut of Aedes aegypti L. (Diptera: Culicidae)
      larvae following exposure to an Annona coriacea (Magnoliales: Annonaceae)
      extract.
AB  - Bioinsecticides are important in the control of disease vectors, but data
      regarding their physiological effects on target insects are incomplete. This
      study describes morphological changes that occur in the midgut of third instar
      Aedes aegypti L. (Diptera: Culicidae) following treatment with a methanolic
      extract of Annona coriacea (Magnoliales: Annonaceae). Dissected midguts were
      subdivided into anterior and posterior regions and analyzed by light and scanning
      electron microscopy. Insects exposed to the extract displayed intense,
      destructive cytoplasmic vacuolization in columnar and regenerative midgut cells.
      The apical surfaces of columnar cells exhibited cytoplasmic protrusions oriented
      toward the lumen, suggesting that these cells could be involved in apocrine
      secretory processes and/or apoptosis. We report that A. coriacea extracts induced
      morphological alterations in the midgut of A. aegypti midgut larvae, supporting
      the use of plant extracts for control of the dengue vector. 

PMID- 23950068
TI  - Status of Aceria guerreronis Keifer (Acari: Eriophyidae) as a pest of coconut in
      the state of Sao Paulo, southeastern Brazil.
AB  - The coconut mite, Aceria guerreronis Keifer, is one of the main pests of coconut
      palms (Cocos nucifera) in northeastern Brazil. The objective of this study was to
      evaluate the levels of the coconut mite and other mites on coconut palms in the
      state of Sao Paulo and to estimate the possible role of predatory mites in the
      control of this pest. The effect of cultivated genotypes and sampling dates on
      the mite populations was also estimated. We sampled attached fruits, leaflets,
      inflorescences, and fallen fruits. The coconut mite was the main phytophagous
      mite found on attached and fallen fruits, with average densities of 110.0 and
      20.5 mites per fruit, respectively. The prevalent predatory mites on attached and
      fallen fruits were Proctolaelaps bulbosus Moraes, Reis & Gondim Jr. and
      Proctolaelaps bickleyi (Bram), both Melicharidae. On leaflets, the tenuipalpids
      Brevipalpus phoenicis (Geijsks) and Tenuipalpus coyacus De Leon and the
      tetranychid Oligonychus modestus (Banks) were the predominant phytophagous mites.
      On both leaflets and inflorescences, the predominant predatory mites belonged to
      the Phytoseiidae. Neoseiulus baraki (Athias-Henriot) and Neoseiulus paspalivorus
      (De Leon), predators widely associated with the coconut mite in northeastern
      Brazil and several other countries, were not found. The low densities of the
      coconut mite in Sao Paulo could be related to prevailing climatic conditions,
      scarcity of coconut plantations (hampering the dispersion of the coconut mite
      between fields), and to the fact that some of the genotypes cultivated in the
      region are unfavorable for its development. 

PMID- 23950069
TI  - Use of geostatistics to determine the spatial distribution and infestation rate
      of leaf-cutting ant nests (Hymenoptera: Formicidae) in eucalyptus plantations.
AB  - One of the fundamental steps in pest sampling is the assessment of the population
      distribution in the field. Several studies have investigated the distribution and
      appropriate sampling methods for leaf-cutting ants; however, more reliable
      methods are still required, such as those that use geostatistics. The objective
      of this study was to determine the spatial distribution and infestation rate of
      leaf-cutting ant nests in eucalyptus plantations by using geostatistics. The
      study was carried out in 2008 in two eucalyptus stands in Paraopeba, Minas
      Gerais, Brazil. All of the nests in the studied area were located and used for
      the generation of GIS maps, and the spatial pattern of distribution was
      determined considering the number and size of nests. Each analysis and map was
      made using the R statistics program and the geoR package. The nest spatial
      distribution in a savanna area of Minas Gerais was clustered to a certain extent.
      The models generated allowed the production of kriging maps of areas infested
      with leaf-cutting ants, where chemical intervention would be necessary, reducing
      the control costs, impact on humans, and the environment. 

PMID- 23950071
TI  - A severe case of cutaneous myiasis in Sao Goncalo, Brazil, and a simple technique
      to extract New World screw-worm Cochliomyia hominivorax (Coquerel) (Diptera:
      Calliphoridae).
AB  - This work describes a severe case of myiasis by Cochliomyia hominivorax
      (Coquerel) in a 59-year-old patient living in an urban area of Sao Goncalo, Rio
      de Janeiro. The patient had an open wound on the right shoulder parasitized by
      287 larvae. In order to remove the larvae, the wound was washed with NaCl and
      solid vaseline was applied onto the wound and covered with gauze and adhesive
      tape. After 90 min, the larvae were killed by asphyxiation and were removed using
      sterile forceps and NaCl. This procedure left the wound completely clean.

PMID- 23950070
TI  - Life histories and fitness of two tuber moth species feeding on native Andean
      potatoes.
AB  - In the inter-Andean valleys of central Peru, two species of tuber moth,
      Phthorimaea operculella (Zeller) and Symmetrischema tangolias (Gyen), often occur
      simultaneously in stored potatoes. Traditional farming communities in the region
      produce a variety of native potatoes for local consumption. These include Solanum
      tuberosum subsp. andigena, the presumed predecessor of commercial potatoes, S.
      tuberosum subsp. tuberosum. In this study, we examined resistance against P.
      operculella in ten native Peruvian potato varieties (Casa blanca, Chispiadita,
      Madre de vaca, Mamaco negro, Misha, Chorisa, Mamaco rosado, Occa papa, Vacapa
      jayllo, and Yana tornasol). We also compared resistance in the first five of
      these varieties against S. tangolias. Varieties with pigmented periderms showed
      moderate resistance (30-40% against P. operculella in Mamaco negro, Mamaco
      rosado, and Yana tornasol and 55% against S. tangolias in Mamaco negro). All the
      other varieties were susceptible to both moth species. Small tubers tended to be
      the most resistant to the attack by both moths; however, this was not related to
      the availability of food for developing larvae, since pupal weight and
      development time were unaffected by the size of tubers. Similar responses by the
      two moths to native potatoes indicate that tuber resistance could be used to
      control the complex of tuber moths that damage potatoes in the Andes. We suggest
      that native potatoes, which are often easily introgressed with commercial
      potatoes, are a potential source of resistance against tuber moths. 

PMID- 23950072
TI  - Brachymeria pandora (Crawford) (Hymenoptera: Chalcididae) as a new parasitoid of
      Thyrinteina leucocerae (Rindge) (Lepidoptera: Geometridae) in Brazil.
AB  - This is the first report of Brachymeria pandora (Crawford) (Hymenoptera:
      Chalcididae)-parasitizing pupae of the eucalyptus defoliator Thyrinteina
      leucocerae (Rindge) (Lepidoptera: Geometridae) in Brazil. 

PMID- 23950073
TI  - Severe Pallister-Hall syndrome with persistent urogenital sinus, renal agenesis,
      imperforate anus, bilateral hypothalamic hamartomas, and severe skeletal
      anomalies.

PMID- 23950074
TI  - Solution-gated graphene transistors for chemical and biological sensors.
AB  - Graphene has attracted much attention in biomedical applications for its
      fascinating properties. Because of the well-known 2D structure, every atom of
      graphene is exposed to the environment, so the electronic properties of graphene
      are very sensitive to charged analytes (ions, DNA, cells, etc.) or an electric
      field around it, which renders graphene an ideal material for high-performance
      sensors. Solution-gated graphene transistors (SGGTs) can operate in electrolytes
      and are thus excellent candidates for chemical and biological sensors, which have
      been extensively studied in the recent 5 years. Here, the device physics, the
      sensing mechanisms, and the performance of the recently developed SGGT-based
      chemical and biological sensors, including pH, ion, cell, bacterial, DNA,
      protein, glucose sensors, etc., are introduced. Their advantages and
      shortcomings, in comparison with some conventional techniques, are discussed.
      Conclusions and challenges for the future development of the field are addressed
      in the end. 

PMID- 23950075
TI  - [Laparoscopic Toupet - fundoplication].
AB  - The laparoscopic fundoplicatio is the "gold standard" among surgical therapy of
      gastrooesophageal reflux disease. In this context the Toupet fundoplicatio is an
      alternative indication to the Nissen fundoplicatio. The lesser dysphagia rate is
      specified as postoperative advantage. To avoid complications, a standardized
      procedure is relevant for a good postoperative outcome, even in more complex
      procedures. In this article, the indications and surgical methods are
      illustrated, as they are performed by the authors. The operation steps are
      demonstrated in addition to the text also in the attached video. 

PMID- 23950076
TI  - [Laudatio. Prof. Dr. med. Dr. h. c. Hans Lippert - professor for surgery at the
      Magdeburg Otto von Guericke University 1993-2013].

PMID- 23950077
TI  - [Surgical treatment of carcinomas of the oesophagogastric junction - results
      achieved in multicentre studies].
AB  - BACKGROUND: Adenocarcinomas of the oesophagogastric junction are increasingly
      being considered as a separated tumour entity. The prognosis is rather poorer
      compared with that for distal gastric cancer. Data from a multicentre study as
      part of research on clinical care aim to reflect the current situation in
      surgical treatment after inauguration of neoadjuvant modalities. PATIENTS AND
      METHOD: As part of the ongoing prospective multicentre observational study QCGC 2
      (German Gastric Cancer Study 2), 544 adenocarcinomas of the oesophagogastric
      junction (AEG 1-3) were registered from 01/01/2007 to 12/31/2009. RESULTS:
      Patients underwent surgical intervention in 108 (76.6 %) of the 141 surgical
      departments which provided data to the study. In 391 patients (82.5 %), R0
      resection was achieved. Almost 60 % of the carcinomas of the oesophagogastric
      junction were approached in departments with no more than 10 of these tumour
      lesions through the whole study period (3 years). Endoscopic ultrasonography was
      performed in 283 cases (53 %); the rate of neoadjuvant treatment was 34.4 % (n =
      187). Intraoperative fresh frozen section was only included in intraoperative
      decision-making in 242 patients (60.8 %). In the revealed heterogeneous spectrum
      of surgical interventions, a limited number of transthoracic approaches (20 %)
      and a mediastinal lymphadenectomy rate of only 47 % were found. Hospital
      lethality was 6.6 %. In the adenocarcinomas of the oesophagogastric junction, a
      significantly lower median survival (25 months) compared with distal gastric
      cancer (38 months) was observed depending on the tumour stage. In addition, 5
      year survival rate of AEG patients (33.1 %) was distinctly lower than for
      patients with distal gastric cancer (41.4 %). There was no significantly better
      survival by neoadjuvant treatment in the group of investigated patients.
      CONCLUSION: The results in the treatment of carcinomas of the oesophagogastric
      junction in the multicentre setting including surgical departments of each
      profile and region even after introduction of multimodal therapeutic concepts are
      not satisfying. In particular, modern diagnostic and surgical strategies need to
      be widely used or their percentage has to be increased. In this context,
      centralisation of the surgical care of this specific tumour entity appears
      reasonable.

PMID- 23950078
TI  - [Hernia repair at the groin - who undergoes which surgical intervention?].
AB  - BACKGROUND: Within the Guidelines of the European Hernia Society (EHS), there are
      disctinct statements about where and how inguinal hernia has to be surgically
      approached. In ASA-I and -II patients, it is recommended to perform the operation
      in an outpatient clinic setting. Male patients older than 30 years of age should
      undergo preferably surgical intervention using a mesh. In this context, there are
      two basic questions: "Are these recommendations already implemented in daily
      surgical practice (?)" and "Are these guidelines the road to success (?)", which
      are to be commented based on i) data from two registries, ii) data obtained in
      the surgical practice of the first author and iii) a selective literature search.
      MATERIAL AND METHODS: An analysis was made of prospectively obtained data from
      two German registries (Herniamed registry [H-med]; Quality Assurance Inguinal
      Hernia Registry [QIHR]) and a consecutive and representative patient cohort of a
      single surgical practice [Surg-Pract] specialised in hernia surgery. Main results
      and concluding remarks are discussed in light of data reported in the literature.
      RESULTS: Proportions of hernia repair in an outpatient clinic setting were
      substantially different among the 3 groups (as follows): H-med (22.3 %), QIHR
      (62.7 %), Surg-Pract (80.5 %) whereas the percentages of ASA-I and -II patients
      differed only slightly: H-med (83.4 %), QIHR (89.5 %) and Surg-Pract (88.3 %).
      Recurrency rates after 12 months were 0.6 % (QIHR) and 0.7 % (Surg-Pract),
      respectively. In Surg-Pract, for 30 % of hernia repairs, "only" suturing for
      reconstruction was used. CONCLUSION: In ASA-I and -II patients, a substantial
      proportion of individuals can be surgically treated in an outpatient clinic
      setting with no disadvantages regarding high surgical quality and favourable
      outcome. Data from the national H-med indicated a much lower percentage of such
      patients than internationally reported and, in addition, a disproportionately
      high rate of endoscopic procedures. Moreover, reimbursement for hernia repair in
      an outpatient clinic setting is much worse in Germany compared with international
      standards, and, interestingly, there is by a factor of 1/3 an above average
      number of hospital beds in Germany compared with the OECD countries.

PMID- 23950079
TI  - [Gender-specific influences on incidence, screening, treatment, and outcome of
      colorectal cancer].
AB  - BACKGROUND: This overview comments on potential gender-specific differences in
      incidence, anatomic site, screening, treatment, and outcome in patients with
      colorectal cancer (CRC). METHOD: For the literature review, the Medline database
      (PubMed) was searched under the key words "colorectal carcinoma AND gender" and
      "gender differences AND colorectal cancer". Publications of the last 9 years
      (2005-2013) were firstly retrieved. RESULTS: CRC is more commonly observed in men
      than in women, with the higher tumour risk for men being limited to the distal
      colon and rectum. Risk factors for the development of CRC include overweight and
      obesity, this relationship is more pronounced for men than for women. The extent
      to which gender is a prognostic factor for patient survival is controversial. A
      better survival of women compared to men is found especially in the younger age
      groups, from which can be derived a protective effect of oestrogens on the
      development of CRC. As for the frequency with which men and women undergo a
      screening of CRC, sometimes higher screening rates have been reported for men
      than women, however, the socio-economic status of persons invited to participate
      has much more influence on screening attendance than gender. An analysis of
      surgical procedures indicates that it is more difficult to perform the low
      anterior resection of the rectum in men than women, with the result that men
      managed by less experienced surgeons are more likely to receive abdominoperineal
      excision. Furthermore, the risk of anastomotic leakage is higher in men than
      women. CONCLUSION: The essential gender difference, however, is the longer life
      expectancy of women compared to men which has been not always clearly (risk
      adjusted) elaborated in the studies available so far. This difference alone can
      already explain at a high rate the poorer prognosis of right-sided colon cancers
      compared to left-sided cancers. Comparable levels of CRC risk are reached in
      women as compared to men at a higher age. This may influence the effectiveness of
      screening programmes and has not been sufficiently examined. Evidence suggests
      the adaptation of screening recommendations to this fact.

PMID- 23950080
TI  - [Portal vein embolisation prior to extended liver resection - current and future
      aspects].
AB  - Extended liver resections are associated with the risk of postoperative liver
      dysfunction up to liver failure. For this reason, prior to extended liver
      resections patients are conditioned in multi-modal therapy regimes. Portal vein
      embolisation is an essential part of such a multi-modal therapy. The aim of this
      intervention is an induction of hypertrophy of the future remnant liver volume.
      Thereby, the risk of postoperative liver failure is decreased. This article
      summarises the actual aspects of portal vein embolisation prior to extended liver
      resections. 

PMID- 23950081
TI  - [Increased requirements for the challenging abdominosurgical management of morbid
      obesity - what does the abdominal surgeon need to know?].
AB  - In the international comparison and in Europe, the Federal Republic of Germany
      belongs to the countries with a very high prevalence of obesity (men, 67.1 %;
      women, 53 %). Among the European countries, the incidence of diabetes mellitus
      type 2 is also high ("Study of the health of adults in Germany" [DEGS]) - Robert
      Koch Institute). Not only for surgeons, this can be considered as a great
      challenge even in usual abdominosurgical interventions. 1. Surgical equipment
      needs to be adapted to the requirements for obese patients. 2. Minimally invasive
      surgery reduces not only complication rates with regard to postsurgical wound
      infection and hernia in such patients, it allows a competent assessment of the
      peritoneal cavity. 3. A great number of surgical tools and instruments can be
      used in normal weight as well as morbidly obese patients with no limitations -
      for conventional (open) surgical interventions, retractor systems should be
      available. 4. With regard to emergency surgery in patients who had formerly
      undergone bariatric surgery, a competent basic knowledge on the usual bariatric
      surgical interventions and the subsequent anatomic consequences as well as the
      more frequent mid- and long-term complications is necessary, which need to be
      partially approached with the surgical intervention. 5. For numerous oncosurgical
      interventions, no differences in postoperative outcome were found between normal
      weight and morbidly obese patients. 

PMID- 23950082
TI  - Automated solid-phase synthesis of a beta-(1,3)-glucan dodecasaccharide.
AB  - beta-Glucans are a group of structurally heterogeneous polysaccharides found in
      bacteria, fungi, algae and plants. beta-(1,3)-D-Glucans have been studied in most
      detail due to their impact on the immune system of vertebrates. The studies into
      the immunomodulatory properties of these glucans are typically carried out with
      isolates that contain a heterogeneous mixture of polysaccharides of different
      chain lengths and varying degrees of branching. In order to determine the
      structure-activity relationship of beta-(1,3)-glucans, access to homogeneous,
      structurally-defined samples of these oligosaccharides that are only available
      through chemical synthesis is required. The syntheses of beta-glucans reported to
      date rely on the classical solution-phase approach. We describe the first
      automated solid-phase synthesis of a beta-glucan oligosaccharide that was made
      possible by innovating and optimizing the linker and glycosylating agent
      combination. A beta-(1,3)-glucan dodecasaccharide was assembled in 56 h in a
      stereoselective fashion with an average yield of 88% per step. This automated
      approach provides means for the fast and efficient assembly of linker
      functionalized mono- to dodecasaccharide beta-(1,3)-glucans required for
      biological studies.

PMID- 23950083
TI  - The incorporation of growth factor and chondroitinase ABC into an electrospun
      scaffold to promote axon regrowth following spinal cord injury.
AB  - Spinal cord injury results in tissue necrosis in and around the lesion site,
      commonly leading to the formation of a fluid-filled cyst. This pathological end
      point represents a physical gap that impedes axonal regeneration. To overcome the
      obstacle of the cavity, we have explored the extent to which axonal substrates
      can be bioengineered through electrospinning, a process that uses an electrical
      field to produce fine fibres of synthetic or biological molecules. Recently, we
      demonstrated the potential of electrospinning to generate an aligned matrix that
      can influence the directionality and growth of axons. Here, we show that this
      matrix can be supplemented with nerve growth factor and chondroitinase ABC to
      provide trophic support and neutralize glial-derived inhibitory proteins.
      Moreover, we show how air-gap electrospinning can be used to generate a
      cylindrical matrix that matches the shape of the cord. Upon implantation in a
      completely transected rat spinal cord, matrices supplemented with NGF and
      chondroitinase ABC promote significant functional recovery. An examination of
      these matrices post-implantation shows that electrospun aligned monofilaments
      induce a more robust cellular infiltration than unaligned monofilaments. Further,
      a vascular network is generated in these matrices, with some endothelial cells
      using the electrospun fibres as a growth substrate. The presence of axons within
      these implanted matrices demonstrates that they facilitate axon regeneration
      following spinal cord injury. Collectively, these results demonstrate the
      potential of electrospinning to generate an aligned substrate that can provide
      trophic support, directional guidance cues and regeneration-inhibitory
      neutralizing compounds to regenerating axons following spinal cord injury.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 23950084
TI  - The Lepidoptera associated with forestry crop species in Brazil: a historical
      approach.
AB  - Despite the long history of forestry activity in Brazil and its importance to the
      national economy, there is still much disorder in the information regarding pests
      of forestry species. Considering the importance of the entomological knowledge
      for the viability of silvicultural management, this work aimed to gather
      information on the species of Lepidoptera associated with forestry crops within
      Brazil using a historical approach. Through a literature review, all registered
      species of Lepidoptera related to forestry crops in Brazil from 1896 to 2010 were
      identified. The historical evaluation was based on the comparison of the number
      of published articles, species richness, and community similarities of the
      Lepidoptera and their associated forest crops, grouped in 10-year samples. A
      total of 417 occurrences of Lepidoptera associated with forestry species were
      recorded, from which 84 species are related with 40 different forestry crops. The
      nocturnal Lepidoptera were dominant on the records, with Eacles imperialis
      magnifica Walker as the most frequent pest species cited. Myrtaceae was the most
      frequent plant family, with Cedrela fissilis as the most cited forestry crop
      species. A successional change in both Lepidoptera species and their host plants
      was observed over the decades. The richness of lepidopteran pest species
      increased over the years, unlike the richness of forestry crop species. This
      increase could be related to the inefficient enforcement of sanitary barriers, to
      the increase of monoculture areas, and to the adaptability of native pests to
      exotic forestry species used in monoculture stands. 

PMID- 23950085
TI  - Habitat fragmentation effects on the orchid bee communities in remnant forests of
      southeastern Brazil.
AB  - The effect of habitat fragmentation on the structure of orchid bee communities
      was analyzed by the investigation of the existence of a spatial structure in the
      richness and abundance of Euglossini species and by determining the relationship
      between these data and environmental factors. The surveys were carried out in
      four different forest fragments and one university campus. Richness, abundance,
      and diversity of species were analyzed in relation to abiotic (size of the area,
      extent of the perimeter, perimeter/area ratio, and shape index) and biotic
      characteristics (vegetation index of the fragment and of the matrix of each of
      the locations studied). We observed a highly significant positive correlation
      between the diversity index and the vegetation index of the fragment, landscape
      and shape index. Our analysis demonstrated that the observed variation could be
      explained mainly by the vegetation index and the size of the fragment. Variations
      in relative abundance showed a tendency toward an aggregated spatial distribution
      between the fragments studied, as well as between the sampling stations within
      the same habitat, demonstrating the existence of a spatial structure on a small
      scale in the populations of Euglossini. This distribution will determine the
      composition of species that coexist in the area after fragmentation. These data
      help in understanding the differences and similarities in the structure of
      communities of Euglossini resulting from forest fragmentation. 

PMID- 23950086
TI  - Differences in coprophilous beetle communities structure in Sierra de Minas
      (Uruguay): a mosaic landscape.
AB  - Coprophilous beetles represent an abundant and rich group with critical
      importance in the functioning of terrestrial ecosystems. Most coprophagous
      beetles have a stenotopic distribution in relation to vegetation types. Because
      of this, they are usually very sensitive to environmental changes and are
      considered well suited as bioindicator organisms. The aim of this study was to
      analyze variations in coprophilous beetle assemblages in natural and
      anthropogenic habitats. Coprophilous beetle communities were sampled monthly for
      1 year using pitfall traps baited with cow dung, in native xeric upland forests,
      15-years-old plantations of Pinus elliottii and pastures in Sierra de Minas,
      Lavalleja, Uruguay. A total of 7,436 beetles were caught and identified to
      species or morphospecies level. The most abundant families were Aphodiidae,
      Scarabaeidae, and Staphylinidae. Differences in species richness, abundance,
      Shannon index, evenness, and dominance were detected between habitats. Abundances
      of most frequent families were significantly higher in both kinds of forests.
      Species richness and diversity of Aphodiidae and Staphylinidae were higher in
      forests, while Scarabaeidae showed the highest richness and diversity in pine
      plantations. Species composition significantly differed between habitats. Uroxys
      terminalis Waterhouse and Ataenius perforatus Harold typified the assemblages in
      native forests and pine plantations and also discriminated both communities
      because of their differential pattern of abundance between habitats. Typifying
      species in pastures were Onthophagus hirculus, Ateuchus robustus (Harold), and
      Ataenius platensis Blanchard. Habitat type had a strong effect on the
      coprophilous beetle community structure and composition.

PMID- 23950087
TI  - Species richness and host specificity among caterpillar ensembles on shrubs in
      the Andes of Southern Ecuador.
AB  - Caterpillar ensembles were sampled on 16 species of shrubs from the family
      Asteraceae and the genus Piper (Piperaceae) in open and forest habitats in the
      Andean montane forest zone of southern Ecuador between August 2007 and May 2009.
      Trophic affiliations of caterpillars to the host plants were confirmed in feeding
      trials. Overall, species richness of herbivorous caterpillars was high (191
      species across all plants), but varied strongly between ensembles associated with
      different plant species (2-96 lepidopteran species per shrub species). Ensembles
      on Piper species were characterized by low effective species numbers and high
      dominance of one or two species of the Geometridae genus Eois Hubner. Low species
      number and high dominance were also found on latex-bearing Erato polymnioides,
      whereas ensembles on two other Asteraceae species were far more diverse and less
      strongly shaped by a few dominant species. The observed diversity patterns fit
      well to the concept that anti-herbivore defenses of plants are the major factors
      regulating associated insect ensembles. Local abundance and geographic range of
      host plants appear to have less influence. Lepidopteran species feeding on
      Asteraceae were found to be more generalistic than those feeding on Piper
      species. We conclude that caterpillar ensembles on most, but not all, studied
      plant species are defined by a small number of dominant species, which usually
      are narrow host specialists. This pattern was more distinct on Piper shrubs in
      forest understory, whereas Asteraceae in disturbed habitats had more open
      caterpillar ensembles. 

PMID- 23950088
TI  - Feeding activity, salivary amylase activity, and superficial damage to soybean
      seed by adult Edessa meditabunda (F.) and Euschistus heros (F.) (Hemiptera:
      Pentatomidae).
AB  - Greenhouse and laboratory studies were conducted to evaluate feeding activity and
      superficial damage to soybean seed by the brown-winged stink bug, Edessa
      meditabunda (F.), and the Neotropical brown stink bug, Euschistus heros (F.).
      Soybean plants (cv. BRS 282), at R6 stage of development were used. Thirty pairs
      of each species were used individually for 48 h. Two daily observations (9:00 AM
      and 3:00 PM) were taken to record the number of bugs (feeding/resting) on plant
      parts. Harvested seeds imbibed in tetrazolium solution were photographed for
      measurement of the damaged surface. Adult E. meditabunda significantly preferred
      soybean stems (19.7 bugs) to pods (2.7). Feeding/resting was similar at 9:00 AM
      (mean number of 28.0 bugs) and 3:00 PM (24.3). Euschistus heros equally
      fed/stayed on stems (7.3 bugs) and pods (6.9), although most bugs (12.3) remained
      on the cage net; feeding/resting on all plant structures amounted to 13.7 bugs at
      9:00 AM and 17.7 bugs at 3:00 PM. Amylase activity was greater for E. heros
      (41.61 +/- 0.89 U/mg) and almost none for E. meditabunda (2.35 +/- 0.14 U/mg).
      The superficial damage to seeds was significantly greater for E. meditabunda (22.
      9 mm(2)) compared to E. heros (12.5 mm(2)). However, E. meditabunda caused less
      shrinkage of the seed tegument, while E. heros damage was deeper and seeds showed
      reduction in size.

PMID- 23950089
TI  - A new species of Allosathes Gaud, Atyeo & Berla (Astigmata: Crypturoptidae) on
      feathers of the Chilean tinamou, Nothoprocta perdicaria (Tinamiformes: Tinamidae)
      in Chile.
AB  - Allosathes anitae n. sp. Casanueva & Gonzalez-Acuna (Astigmata: Crypturoptidae),
      collected on the Chilean tinamou Nothoprocta perdicaria (Tinamiformes: Tinamidae)
      from different localities of the Nuble Province, Chile, is described. Comments on
      its affinities and differences with Allosathes anepiandrius Gaud, Atyeo & Berla
      are also included. 

PMID- 23950090
TI  - The Antennal sensilla of Oxelytrum erythrurum (Blanchard) and Oxelytrum apicale
      (Brulle) (Coleoptera: Silphidae).
AB  - The typology and placement of antennal sensilla of the carrion beetles Oxelytrum
      erythrurum (Blanchard) and Oxelytrum apicalis (Brulle) (Coleoptera: Silphidae)
      were studied using scanning electron microscopy. Two types of sensilla chaetica,
      two types of sensilla trichodea, four types of sensilla basiconica, one type of
      sensilla coeloconica, and an unidentified type of sensillum were found in both
      species. Sensilla chaetica type 1 are found on the antennomeres proximal to
      antennal club (A1-A8); chaetica type 2 are found on the club (A9-A11). Sensilla
      trichodea are found on A9-A11; one type (T1) is found on the proximal portion of
      the club, the other type (T2) on the apical portion. Basiconica type 1 are found
      on the dorsal surface of A9-A11; they are much denser on the apical portion of
      the antennal club than on the proximal. In O. erythrurum, a nocturnal species of
      the Chaco-Pampean plain, T2 two are found on A10 and A11. In Oxelytrum apicale, a
      mountain species, probably diurnal, only A11 bears T2, but they are denser than
      in the other species. It is suggested that O. apicale depends more on contact
      chemoreception than O. erythrurum. The ventral surface of the antennal clubs
      shows no remarkable difference between species. 

PMID- 23950091
TI  - Resistance of maize landraces to the maize weevil Sitophilus zeamais Motsch.
      (Coleoptera: Curculionidae).
AB  - The maize weevil Sitophilus zeamais Motsch. is an important pest of maize that
      attacks the grain both in the field and during storage. The damage caused by the
      maize weevil S. zeamais on maize landraces, Amarelo Antigo, Asteca, Caiano,
      Carioca, and Ferrinho, was evaluated by no-choice tests under laboratory
      conditions. The commercial varieties Sol da Manha, BR 106, BR 451, and the
      synthetics PC 0203 and PC 9903 were evaluated for comparisons with the maize
      landraces. The parameters evaluated were susceptibility index, number of weevil
      progeny, development time, weevil progeny dry weight, and grain dry weight loss.
      The landraces were more susceptible to the maize weevil as compared to the
      commercial varieties. Based on the cluster analysis, two groups of susceptibility
      to the maize weevil were observed: one of more susceptible populations formed by
      local landraces and BR 451, and another less susceptible, with commercial
      varieties, synthetics, and the landrace Amarelo. 

PMID- 23950092
TI  - Population of Scaptocoris castanea Perty (Hemiptera: Cydnidae) in a crop
      livestock integration system.
AB  - The population of the brown root stink bug, Scaptocoris castanea Perty, was
      studied in a crop-livestock integration system. This integrated system consisted
      of corn crop associated with Brachiaria decumbens pasture at the Unidade de
      Pesquisa e Desenvolvimento, in Sao Jose do Rio Preto (49 degrees 26' W; 20
      degrees 49' S), state of Sao Paulo, Brazil. In each plot of the integrated crop
      livestock system, which was consisted of six treatments and four replicates, four
      0.25 m(2) and 0.30-m-deep samples of soil and roots were taken for analysis.
      These samples were stratified in 0.10-m layers, in which the number of nymphs and
      adults of S. castanea were assessed. These evaluations occurred monthly, from
      November 2008 to April 2009. The number of brown bug nymphs and adults was higher
      in areas where corn was cultivated for two consecutive years and in plots where
      pasture was renewed every 2 years. Lower insect population densities were
      observed in plots that remained as Brachiaria pasture. Therefore, S. castanea
      population is larger in integrated crop-livestock system (corn crop associated
      with B. decumbens), with no tillage.

PMID- 23950093
TI  - Toxicity of Porella chilensis sesqui- and diterpenoids against larvae of the corn
      pest Spodoptera frugiperda (J.E. Smith) (Lepidotera: Noctuidae).
AB  - Porella, the largest genus of the family Porellaceae (Hepaticae) is widespread in
      the tropical and subtropical regions of South America. Most Porella species are
      rich sources of sesqui- and diterpenoids, many of which show interesting
      biological activities. Secondary metabolites produced by plants can interact with
      insects and act as antifeedants and growth regulators affecting hormone and
      nervous systems as well as stomach and muscle tissues. A previous chemical
      investigation of a Patagonian collection of Porella chilensis yielded sesqui- and
      diterpenoids that were now evaluated for their effects against Spodoptera
      frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), a serious pest affecting corn
      crops mainly in the Americas. Four pinguisanes (1-4), three fusicoccanes (5-7),
      and one aromadendrane (8) from P. chilensis displayed larvicidal activity against
      S. frugiperda when incorporated to the larval diet at 100 and 200 MUg/g of diet
      with a significant decrease in the larval growing rate. The observed effects were
      in part produced by severe alterations of the epithelial cells of the midgut as
      indicated by our histological studies.

PMID- 23950094
TI  - Enzymatic response of the eucalypt defoliator Thyrinteina arnobia (Stoll)
      (Lepidoptera: Geometridae) to a bis-benzamidine proteinase Inhibitor. i.
AB  - Ingestion of proteinase inhibitors leads to hyperproduction of digestive
      proteinases, limiting the bioavailability of essential amino acids for protein
      synthesis, which affects insect growth and development. However, the effects of
      proteinase inhibitors on digestive enzymes can lead to an adaptive response by
      the insect. In here, we assessed the biochemical response of midgut proteinases
      from the eucalypt defoliator Thyrinteina arnobia (Stoll) to different
      concentrations of berenil, a bis-benzamidine proteinase inhibitor, on eucalyptus.
      Eucalyptus leaves were immersed in berenil solutions at different concentrations
      and fed to larvae of T. arnobia. Mortality was assessed daily. The proteolytic
      activity in the midgut of T. arnobia was assessed after feeding on plants sprayed
      with aqueous solutions of berenil, fed to fifth instars of T. arnobia for 48 h
      before midgut removal for enzymatic assays. Larvae of T. arnobia were able to
      overcome the effects of the lowest berenil concentrations by increasing their
      trypsin-like activity, but not as berenil concentration increased, despite the
      fact that the highest berenil concentration resulted in overproduction of trypsin
      like proteinases. Berenil also prevented the increase of the cysteine proteinases
      activity in response to trypsin inhibition.

PMID- 23950096
TI  - New distribution records for Cassidinae gyllenhal (Coleoptera: Chrysomelidae).
AB  - Range extensions are provided for four Neotropical tortoise beetle species. A new
      host plant for a potentially new species of Delocrania Guerin-Meneville is also
      provided. 

PMID- 23950095
TI  - On the use of classic epidemiological formulae for estimating the intensity of
      endemic malaria transmission by vectors in the Amazon.
AB  - Although various reports have described entomological inoculation rates of
      malaria vector species, most were limited to providing descriptive field data.
      Here, we report biting rates and survival data for two important malaria vectors
      in the Amazon, Anopheles darlingi (Root) and Anopheles albitarsis E (Lynch
      Arribalzaga) (Diptera: Culicidae), in the state of Roraima, Brazil. We calculated
      theoretical sporozoite infection rates and critical vector biting rates for these
      species during 1 year, comprising six bimestrial collections. Anopheles darlingi
      had higher sporozoite rates and lower critical biting rates, indicating that it
      would be the more efficient vector at the beginning of epidemic malaria
      transmission. Our data, together with compiled information from the literature in
      the Amazon, suggest that epidemic malaria transmission may be initiated by the
      primary vector, such as A. darlingi, while secondary vectors, such as A.
      albitarsis E, may only become epidemiologically important when there is an
      increase in the prevalence of human malaria. We propose that mathematical
      modeling may be able to quantify the relative importance of secondary vector
      species in malaria epidemiology.

PMID- 23950097
TI  - Risk and protective factors in the origin of conotruncal defects of heart--a
      population-based case-control study.
AB  - Congenital heart defect (CHD) cases have been evaluated together as a group in
      some previous epidemiological studies. However, different CHD entities have
      different etiologies, and the underlying causes are unclear in the vast majority
      of patients. Thus the aim of this study was to analyze the possible association
      of different maternal diseases with the risk of four types of conotruncal defects
      (CTD), that is, truncus arteriosus, d-transposition of the great arteries,
      tetralogy of Fallot, and double-outlet right ventricle based on autopsy or
      surgical report diagnosis. Acute and chronic diseases with related drug
      treatments and peri-conceptual folic acid or multivitamin supplementations were
      compared in mothers of 598 CTD cases, of 902 matched controls, and 38,151
      population controls without any defects, and with 20,896 malformed controls with
      other isolated non-cardiac defects in the population-based large dataset of the
      Hungarian Case-Control Surveillance of Congenital Abnormalities. Mothers who had
      medically recorded influenza and the common cold with secondary complications in
      the prenatal maternity logbook during the second and/or third gestational months
      were associated with a higher risk of CTD (OR with 95% CI: 2.22, 1.19-3.88). The
      common denominator of these maternal diseases may be high fever, which could be
      prevented by antifever therapies. On the other hand, high doses of medically
      recorded folic acid in early pregnancy were able to reduce the birth prevalence
      of CTD (OR with 95% CI: 0.54, 0.39-0.73), and this reduction was significant in
      transposition of the great arteries (0.46, 0.29-0.71) as well. In conclusion,
      high fever related maternal diseases may have a role in the origin of CTD, while
      high doses of folic acid in early pregnancy were able to reduce of CTD,
      particularly transposition of great vessels.

PMID- 23950098
TI  - Pyrimidine-5-carbonitriles II: synthesis and antimicrobial activity of novel 6
      alkyl-2,4-disubstituted pyrimidine-5-carbonitriles.
AB  - New series of 6-alkyl-2,4-disubstituted pyrimidine-5-carbonitriles namely, 6
      alkyl-2-thiouracil-5-carbonitriles 4c,d, 6-alkyl-2-arylmethylsulfanyl-3,4-dihydro
      4-oxopyrimidine-5-carbonitriles 5a-p, 6-alkyl-2-(2-methoxyethylsulfanyl)-3,4
      dihydro-4-oxopyrimidine-5-carbonitriles 6a-d, 6-alkyl-2-benzyloxymethylsulfanyl
      3,4-dihydro-4-oxopyrimidine-5-carbonitriles 7a-c, 6-alkyl-2-(5-nitrofuran-2
      ylmethylsulfanyl)-3,4-dihydro-4-oxopyrimidine-5-carbonitriles 8a-d, 6-alkyl-4
      arylthio-2-(benzylsulfanyl)pyrimidine-5-carbonitriles 10a, b and 2-benzylsulfanyl
      4-[4-(2-methoxyphenyl)-1-piperazinyl]-6-pentylpyrimidine-5-carbonitrile 11, were
      synthesized and tested for in vitro activities against a panel of Gram-positive
      and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans.
      Compounds 4d, 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i, 5j, 5k, 5 l, 5p, 7a, 7b, 7c, 8a,
      8b, 8c, 8d and 11 -displayed marked antibacterial activity particularly against
      the tested Gram-positive bacteria. Meanwhile, none of these compounds were proved
      to be active against Candida albicans.

PMID- 23950099
TI  - Synthesis, structure activity relationships and biological activity evaluation of
      novel spirocyclic thiazolidin-4-ones as potential anti-breast cancer and
      epidermal growth factor receptor inhibitors.
AB  - A series of triazaspiro[4.5]dec-8-ene benzylidine derivatives containing
      thiazolidinone ring system (6-18) have been designed, synthesized and their
      biological activities evaluated as potential epidermal growth factor receptor
      inhibitors. Among them, 9-amino-2-(4-nitrobenzylidene)-3-oxo-4-phenyl-7-thioxo-1
      thia-4,6,8-triazaspiro[4.5]dec-8-ene-10-carbonitrile (18) displayed the most
      potent inhibitory activity (IC50=6.355 uM). Antiproliferative assay results
      indicated that compound 18 exhibited moderate antiproliferative activity against
      MCF-7 cell line in vitro; with GI50 value of 30.6 uM. In addition, compounds 7
      and 15 displayed the highest antiproliferative activity at a common GI50 value of
      10.8 uM. Docking simulation was performed to determine the probable binding model
      and to pursuit information regarding the activity of compound 18. Based on the
      preliminary results, compound 18 could be used as an attractive building block
      for designing potential epidermal growth factor receptor inhibitors. 

PMID- 23950100
TI  - Floating-pulsatile release multiparticulate system for chronopharmacotherapy:
      effect of some hydrophobic additives on the buoyancy and release behavior of
      particles.
AB  - A blend of floating and pulsatile principles of a drug delivery system would have
      the advantage that a drug can be released in the upper gastrointestinal (GI)
      tract after a lag period, which is anticipated for chronotherapy. In this study,
      microballoons were prepared by an emulsion solvent diffusion technique using
      Eudragit S100, and hydrophobic additive (magnesium stearate, stearic acid or
      talc) for time- and site-specific drug release of piroxicam. The effect of
      hydrophobic additives on the production yield of floating microparticles, buoyant
      ability for 8 h, release of drug in simulated GI fluids (simulated gastric fluid
      [SGF] and simulated intestinal fluid [SIF]), mean particle size, apparent
      particle density, encapsulation efficiency of drug and physical state of
      incorporated drug were studied. Both production yield and buoyancy of the
      microballoons were affected by additives in the following order: magnesium
      stearate, stearic acid>free-additive>talc. The observed difference in yield and
      the buoyancy of the microballoons could be attributed to the hydrophobic
      character of the additives and the shell rigidity of the obtained microballoons.
      Incorporation of hydrophobic additives in the microballoons was found to impart
      the desired release properties to the microballoons by providing a 2-phase
      release pattern with initial slow release (5-6%) through 8 h in SGF followed by
      rapid pulse release (>92%) in SIF through 15 min. The microballoons co-formulated
      with magnesium stearate or stearic acid, combining excellent buoyancy and
      suitable drug release pattern of piroxicam, could be useful in
      chronopharmacotherapy in arthritis.

PMID- 23950101
TI  - Dioscin prevents the mitochondrial apoptosis and attenuates oxidative stress in
      cardiac H9c2 cells.
AB  - To determine if dioscin protects cardiac cells from ischemia/reperfusion (I/R)
      injury by preventing apoptosis.Cardiac H9c2 cells were subjected to simulated
      I/R. Cell viability was evaluated by the methyl thiazolyl tetrazolium (MTT)
      colorimetry assay. Reactive oxygen species (ROS) were detected with
      dichlorodihydrofluorescein (DCF). Apoptosis was evaluated with flow cytometric
      assay. Rhodamine 123 (Rho123) was used to measure mitochondrial membrane
      potential (DeltaPsim). ELISA was used to detect cytochrome c (Cyt-c) release from
      mitochondria to the cytosol. Bax and Bcl-2 mRNA expressions were measured with RT
      PCR.Dioscin reduced cell death and lactate dehydrogenase (LDH) release in cells
      subjected to I/R. I/R induced apoptosis and cytochrome c release from
      mitochondria to the cytosol and this was prevented by dioscin. In support,
      dioscin decreased Bax but increased Bcl-2 mRNA expression. Dioscin prevented I/R
      induced dissipation of DeltaPsim. Finally, dioscin increased superoxide dismutase
      (SOD) expression but reduced intracellular ROS and malondialdehyde (MDA)
      levels.Dioscin protects H9c2 cells from H/R injury by modulating the
      mitochondrial apoptotic pathway through attenuation of oxidative stress. 

PMID- 23950102
TI  - Synthesis, antimicrobial evaluation and QSAR studies of p-hydroxy benzoic acid
      derivatives.
AB  - In the present study, a series of p-hydroxy benzoic acid derivatives (1-29) was
      synthesized and tested for its antimicrobial potential. Results of antimicrobial
      studies indicated that in general, Schiff bases were found to be more active as
      compared to esters and compound 14 was found to be most potent antimicrobial
      agent (pMICam=1.50 uM/ml). QSAR study was performed in order to understand the
      relationship between antimicrobial activity and changes in the molecular
      structures which indicated that antimicrobial activity of the synthesized
      compounds was governed by valence first order molecular connectivity index
      (1chiv), Kier's alpha first order shape index (kappaalpha1), Kier's first order
      shape index (kappa1) and Balaban topological index (J). 

PMID- 23950103
TI  - Underwater-transparent nanodendritic coatings for directly monitoring cancer
      cells.
AB  - Underwater-transparent nanodendritic coatings are easily fabricated by a three
      step template process. After modification with anti-EpCAM, the coatings exhibit
      the capability for efficiently capturing rare number of cancer cells from whole
      blood. On the other hand, the unique underwater transparency enables the coatings
      to directly monitor captured cancer cells by optical imaging. 

PMID- 23950104
TI  - High-nitrogen-based pyrotechnics: perchlorate-free red- and green-light
      illuminants based on 5-aminotetrazole.
AB  - Prototype testing of perchlorate-free hand-held signal illuminants for the US
      Army's M126 A1 red-star and M195 green-star parachute illuminants are described.
      Although previous perchlorate-free variants for these items have been developed
      based on high-nitrogen compounds that are not readily available, the new
      formulations consist of anhydrous 5-aminotetrazole as the suitable perchlorate
      replacement. Compared to the perchlorate-containing control, the disclosed
      illuminants exhibited excellent stabilities toward various ignition stimuli and
      had excellent pyrotechnic performance. The illuminants are important from both
      military and civil fireworks perspectives, as the perchlorate-free nature of the
      illuminants adequately address environmental concerns associated with perchlorate
      containing red- and green-light-emitting illuminants. 

PMID- 23950105
TI  - Optimization of platelet-rich plasma and its effects on the recovery of erectile
      function after bilateral cavernous nerve injury in a rat model.
AB  - Platelet-rich plasma (PRP) containing autologous growth factors is applied in
      regenerative medicine, but the lack of an optimized PRP preparation protocol
      causes unstable therapeutic effects. The aim of this study was to optimize the
      PRP preparation method and compare the effects of PRP from different preparation
      methods in restoration of erectile function in a rat model. The in vivo
      experiments used Sprague-Dawley male rats (n = 24), which were randomly divided
      into four groups of equal numbers: group I underwent sham operation, while the
      remaining three groups underwent bilateral CN crush. Crush injury groups were
      treated at the time of injury with an application of general PRP, optimized PRP
      [with the largest amount of platelet-derived growth factor (PDGF)-AB] or normal
      saline-only injection in the corpus cavernosum, respectively. Four weeks later,
      erectile function was assessed by CN electrosimulation, and penile tissue was
      collected for histology. Results demonstrated that in the PRP group prepared with
      the ACD-A anticoagulant, chitosan and incubated at -20 degrees C for 15 days had
      the largest amount of PDGF-AB and showed a synergistic effect on release (p <
      0.05). Functional outcome measurement and immunofluorescence staining for the
      dorsal nerve revealed that improvement after bilateral CN injury occurred in the
      optimized PRP group (p < 0.05). It was concluded that optimized PRP with a high
      level of growth factors was more stable, and its injection into the corpus
      cavernosum facilitated recovery of erectile function. Copyright (c) 2013 John
      Wiley & Sons, Ltd.

PMID- 23950107
TI  - Nitrergic neurons in the spinal cord of the bottlenose Dolphin (Tursiops
      truncatus).
AB  - Nitric oxide (NO) is a freely diffusible gaseous neurotransmitter generated by a
      selected population of neurons and acts as a paracrine molecule in the nervous
      system. NO is synthesized from l-arginine by means of the neuronal nitric oxide
      synthase (nNOS), an enzyme requiring nicotine adenine dinucleotide phosphate
      (NADPH) as cofactor. In this study, we used histochemical and immunohistochemical
      techniques to investigate the distribution of NADPH-diaphorase (NADPH-d) and nNOS
      in the spinal cord of the bottlenose dolphin (Tursiops truncatus). Cells with a
      fusiform-shaped somata were numerous in the laminae I and II. The
      intermediolateral horn showed darkly-stained cells with a multipolar morphology.
      Neurons with a multipolar or fusiform morphology were observed in the ventral
      horn. Multipolar and fusiform neurons were the most common cell types in lamina
      X. Nitrergic fibers were numerous especially in the dorsal and intermediolateral
      horns. The presence of nitrergic cells and fibers in different laminae of the
      spinal cord suggests that NO may be involved in spinal sensory and visceral
      circuitries, and potentially contribute to the regulation of the complex retia
      mirabilia.

PMID- 23950106
TI  - Germline mosaicism does not explain the maternal age effect on trisomy.
AB  - A variety of hypotheses have been proposed to explain the association between
      trisomy and increasing maternal age in humans, virtually all of which assume that
      the underlying mechanisms involve meiotic errors. However, recently Hulten and
      colleagues [Hulten et al., 2010b] proposed a provocative model-the Oocyte
      Mosaicism Selection Model (OMSM)-that links age-dependent trisomy 21 to pre
      meiotic errors in the ovary. Specifically, they propose that nondisjunctional
      events occur in a proportion of germ cells as they mitotically proliferate,
      resulting in mosaicism for trisomy 21. Assuming that the presence of an
      additional chromosome 21 delays meiotic progression, these cells would be
      ovulated later in reproductive life, resulting in an age-dependent increase in
      aneuploid eggs. Because this model has important clinical implications, we
      initiated studies to test it. We first analyzed oocytes from two trisomy 21
      fetuses, combining immunostaining with FISH to determine the likelihood of
      detecting the additional chromosome 21 at different stages of meiosis. The
      detection of trisomy was enhanced during the earliest stage of prophase
      (leptotene), before homologs synapsed. Accordingly, in subsequent studies we
      examined the chromosome content of leptotene oocytes in seven second trimester
      female fetuses, analyzing three chromosomes commonly associated with human
      trisomies (i.e., 13, 16, and 21). In contrast to the prediction of the OMSM, we
      found no evidence of trisomy mosaicism for any chromosome. We conclude that
      errors in pre-meiotic germ cells are not a major contributor to human aneuploidy
      and do not provide an explanation for the age-related increase in trisomic
      conceptions.

PMID- 23950108
TI  - A biomechanical analysis of controllable intraoperative variables affecting the
      strength of rotator cuff repairs at the suture-tendon interface.
AB  - BACKGROUND: The tissue-suture interface remains the weakest aspect of a rotator
      cuff repair, highlighting the importance of identifying techniques to improve
      stitch strength. Choice of suture-passing devices, size of the tissue bite, and
      stitch configuration are variables that may influence stitch strength and
      therefore repair stability. PURPOSE: To evaluate the effect that size of the
      tissue penetrator device and tissue bite size have upon the holding strength of
      commonly used stitches. STUDY DESIGN: Controlled laboratory study. METHODS: Three
      different-sized tissue-penetrating devices, small circular, midsized circular,
      and large rectangular, were used to place sutures in 192 infraspinatus tendon
      grafts of sheep. Tissue bite sizes of either 0.5 cm or 1.0 cm for 4 different
      stitches, a simple, mattress, modified Mason-Allen (MMA), and massive cuff (MAC)
      stitch, were tested. Grafts were cyclically loaded and then loaded to failure.
      Mixed multivariate regression analysis was used to test the effect of instrument,
      bite size, and stitch configuration on peak-to-peak displacement, cyclic
      elongation, and load to failure. RESULTS: The average ultimate load to failure
      with the smallest penetrating device was 112 N, significantly higher than with
      both the midsized (95 N) and large devices (91 N) (P < .001). The average load to
      failure was 31 N higher for a 1.0-cm bite size when compared with a 0.5-cm bite
      size (P < .001). The largest load-to-failure differences were found with the type
      of stitch placed: simple, 48 N; mattress, 69 N; MMA, 130 N; and MAC, 152 N (all P
      < .02). For simple and mattress stitches, each additional pass of the suture
      increased the load to failure by 21 N. In MMA and MAC stitches, an additional
      pass resulted in an increase in the load to failure by 50 N. Cyclic elongation
      did not differ by instrument type (all P > .5). The elongation of stitches with a
      1.0-cm bite size was 0.14 mm higher than stitches with a 0.5-cm bite size (P <
      .001). No meaningful difference in peak-to-peak displacement was seen for bite
      size, instrument type, or stitch construct. CONCLUSION: The strength of rotator
      cuff stitches was significantly affected by the different-sized tissue
      penetrating instruments and size of the bite. However, the greatest predictor of
      time-zero stitch strength is the type of stitch placed. CLINICAL RELEVANCE: This
      study highlights the importance of stitch configuration in the repair of rotator
      cuff tears.

PMID- 23950109
TI  - Biomechanical characteristics of 3 pivot-shift maneuvers for the anterior
      cruciate ligament-deficient knee: in vivo evaluation with an electromagnetic
      sensor system.
AB  - BACKGROUND: A disadvantage of pivot-shift maneuvers is that the examiner has to
      subjectively evaluate the degree of pivot shift observed. It is unknown whether
      the various maneuvers are biomechanically identical. PURPOSE: To compare
      biomechanical features of 3 clinical maneuvers for the anterior cruciate ligament
      (ACL)-deficient knee: the pivot-shift test, the jerk test, and the N-test. STUDY
      DESIGN: Controlled laboratory study. METHODS: A total of 28 patients with an
      isolated ACL injury were examined by use of 3 pivot-shift maneuvers (pivot-shift
      test, jerk test, and N-test). An electromagnetic sensor system was used to
      evaluate the 3-dimensional knee kinematics of each patient's injured and
      uninjured knees during each maneuver. Peak coupled anterior tibial translation
      (pCAT) and maximal acceleration of posterior translation (APT) were measured
      relative to results during a flexion-extension motion in each test. RESULTS: The
      pCAT of the pivot-shift test was significantly greater than that of both the jerk
      test and the N-test (P = .0020 and P < .0001, respectively); there was no
      statistical difference in pCAT between the jerk test and the N-test. The APT of
      the N-test was significantly greater than that of both the pivot-shift test and
      the jerk test (P < .0001), while there was no statistical difference between the
      pivot-shift and the jerk tests. There was no correlation between pCAT and APT in
      each test. CONCLUSION: The pivot-shift test, jerk test, and N-test have different
      biomechanical characteristics to induce the pivot-shift phenomenon in the ACL
      deficient knee. The pivot-shift test produced the largest side-to-side difference
      in pCAT, whereas the N-test provoked the largest side-to-side difference in APT.
      CLINICAL RELEVANCE: The biomechanical differences in pivot-shift maneuvers are
      caused by technical differences, and clinicians should understand these
      biomechanical differences while practicing the maneuvers. The electromagnetic
      sensor system is clinically useful for quantifying the pivot-shift phenomenon.

PMID- 23950110
TI  - Localization microscopy coming of age: from concepts to biological impact.
AB  - Super-resolution fluorescence imaging by single-molecule photoactivation or
      photoswitching and position determination (localization microscopy) has the
      potential to fundamentally revolutionize our understanding of how cellular
      function is encoded at the molecular level. Among all powerful, high-resolution
      imaging techniques introduced in recent years, localization microscopy excels
      because it delivers single-molecule information about molecular distributions,
      even giving absolute numbers of proteins present in subcellular compartments.
      This provides insight into biological systems at a molecular level that can yield
      direct experimental feedback for modeling the complexity of biological
      interactions. In addition, efficient new labeling methods and strategies to
      improve localization are emerging that promise to achieve true molecular
      resolution. This raises localization microscopy as a powerful complementary
      method for correlative light and electron microscopy experiments. 

PMID- 23950111
TI  - p120-catenin in cancer - mechanisms, models and opportunities for intervention.
AB  - The epithelial adherens junction is an E-cadherin-based complex that controls
      tissue integrity and is stabilized at the plasma membrane by p120-catenin (p120,
      also known as CTNND1). Mutational and epigenetic inactivation of E-cadherin has
      been strongly implicated in the development and progression of cancer. In this
      setting, p120 translocates to the cytosol where it exerts oncogenic properties
      through aberrant regulation of Rho GTPases, growth factor receptor signaling and
      derepression of Kaiso (also known as ZBTB33) target genes. In contrast, indirect
      inactivation of the adherens junction through conditional knockout of p120 in
      mice was recently linked to tumor formation, indicating that p120 can also
      function as a tumor suppressor. Supporting these opposing functions are findings
      in human cancer, which show that either loss or cytoplasmic localization of p120
      is a common feature in the progression of several types of carcinoma. Underlying
      this dual biological phenomenon might be the context-dependent regulation of Rho
      GTPases in the cytosol and the derepression of Kaiso target genes. Here, we
      discuss past and present findings that implicate p120 in the regulation of cancer
      progression and highlight opportunities for clinical intervention. 

PMID- 23950112
TI  - Complete genome sequences of newcastle disease virus strains isolated from three
      different poultry species in china.
AB  - In 2000, three Newcastle disease virus (NDV) strains were isolated from outbreaks
      of infection in layers, ducklings, and geese in the same region of China during
      the same time period. Here, we report their complete genome sequences, which
      belong to the NDV genotype VIId. This discovery might provide clues as to the
      evolution of the NDVs of different avian origins. 

PMID- 23950113
TI  - Draft Genome Sequence of Klebsiella pneumoniae Isolate PR04.
AB  - Klebsiella pneumoniae PR04 was isolated from a patient hospitalized in Malaysia.
      The draft genome sequence of K. pneumoniae PR04 shows differences compared to the
      reference sequences of K. pneumoniae strains MGH 78578 and NTUH-K2044 in terms of
      their genomic structures. 

PMID- 23950114
TI  - Metagenomic sequencing of prokaryotic microbiota from tropical surface seawater.
AB  - Tropical seawater harbors a rich diversity of microorganisms as a result of its
      nutrient-rich environment, constant supply of sufficient sunlight, and warm
      climate. In this report, we present the complexity of the microbial diversity of
      the surface seawater of the Georgetown coast as determined using next-generation
      sequencing technology. 

PMID- 23950115
TI  - Complete Genome Sequence of Serratia liquefaciens Strain ATCC 27592.
AB  - We report the complete genome sequence of Serratia liquefaciens strain ATCC
      27592, which was previously identified as capable of growth under low-pressure
      conditions. To the best of our knowledge, this is the first announcement of the
      complete genome sequence of an S. liquefaciens strain. 

PMID- 23950116
TI  - Noncontiguous Genome Sequence of Mycobacterium septicum Strain DSM 44393T.
AB  - The rapidly growing Mycobacterium septicum rarely causes pulmonary infections. We
      report here the draft genome sequence of M. septicum strain DSM 44393(T),
      isolated from catheter-related bacteremia and initially identified as a member of
      Mycobacterium fortuitum. 

PMID- 23950117
TI  - Draft Genome Sequence of the Virulent Avibacterium paragallinarum Serotype A
      Strain JF4211 and Identification of Two Toxins.
AB  - Avibacterium paragallinarum is an important pathogen of chicken livestock causing
      infectious coryza. Here, we report the draft genome sequence of the virulent A.
      paragallinarum serotype A strain JF4211 (2.8 Mbp and G+C content of 41%) and the
      two toxin operons discovered from the annotation of the genome. 

PMID- 23950118
TI  - Draft Genome Sequence of the Virulent Clostridium chauvoei Reference Strain
      JF4335.
AB  - Clostridium chauvoei is the etiological agent of blackleg, a disease of cattle
      and sheep with high mortality rates, causing severe economic losses in livestock
      production. Here, we report the draft genome sequence of the virulent C. chauvoei
      strain JF4335 (2.8 Mbp and 28% G+C content) and the annotation of the genome. 

PMID- 23950119
TI  - Draft Genome Sequence of Lignocellulose-Degrading Thermophilic Bacterium
      Geobacillus sp. Strain WSUCF1.
AB  - Geobacillus sp. strain WSUCF1 is a thermophilic spore-forming member of the
      phylum Firmicutes, isolated from a soil sample collected from the compost
      facility. We report the draft genome sequence of this isolate with an estimated
      genome size of 3.4 Mb. The genome sequence of this isolate revealed several genes
      encoding glycoside hydrolases, making it a potential candidate for plant biomass
      degradation. 

PMID- 23950120
TI  - Genome Sequence of Klebsiella oxytoca SA2, an Endophytic Nitrogen-Fixing
      Bacterium Isolated from the Pioneer Grass Psammochloa villosa.
AB  - Klebsiella oxytoca strain SA2 is an endophytic nitrogen-fixing bacterium isolated
      from the pioneer grass Psammochloa villosa, which grows in the moving sand dunes
      of Ordos Plateau, China. The SA2 genome sequence provides the genetic background
      for understanding its endophytic lifestyle and survival in association with grass
      in nitrogen-poor environments. 

PMID- 23950122
TI  - Complete Genome Sequence of emm Type 14 Streptococcus pyogenes Strain HSC5.
AB  - Streptococcus pyogenes causes a greater diversity of human disease than any other
      bacterial pathogen. Here, we present the complete genome sequence of the emm type
      14 S. pyogenes strain HSC5. This strain is a robust producer of the cysteine
      protease SpeB and is capable of producing infection in several different animal
      models. 

PMID- 23950121
TI  - High-Quality Draft Genome Sequence of Pseudomonas syringae pv. Syringae Strain
      SM, Isolated from Wheat.
AB  - Pseudomonas syringae is one of the most widespread plant pathogens that can cause
      significant damage to crop plantations. Here, we announce a noncontiguous
      finished genome sequence of Pseudomonas syringae pv. syringae strain SM, isolated
      from hexaploid wheat. The genome sequence revealed the smallest described
      complement of type III effectors. 

PMID- 23950123
TI  - Draft Genome Sequence of Clostridium tyrobutyricum Strain UC7086, Isolated from
      Grana Padano Cheese with Late-Blowing Defect.
AB  - Clostridium tyrobutyricum is considered the main agent of late-blowing defect in
      the production of hard cheese. Here, we described the draft genome sequences and
      annotation of C. tyrobutyricum strain UC7086, which was isolated from Grana
      Padano cheese with blowing defect, and C. tyrobutyricum DSM 2637 type strain in a
      comparative study. 

PMID- 23950124
TI  - Genome Sequence of a Novel Polymer-Grade L-Lactate-Producing Alkaliphile,
      Exiguobacterium sp. Strain 8-11-1.
AB  - Exiguobacterium sp. strain 8-11-1 is a newly isolated alkaliphile, which was
      reported to efficiently produce l-lactate using NaOH as the neutralizing agent.
      Here, we present the first 2.9-Mb assembly of its genome sequence, which may
      provide useful information related to its efficient lactate production and sodium
      ion tolerance capacities. 

PMID- 23950125
TI  - Genome Sequence of an Epidemic Isolate of Mycobacterium abscessus subsp. bolletii
      from Rio de Janeiro, Brazil.
AB  - Multiple isolates of Mycobacterium abscessus subsp. bolletii, collectively called
      BRA100, were associated with outbreaks of postsurgical skin infections across
      various regions of Brazil from 2003 to 2009. We announce the draft genome
      sequence of a newly sequenced BRA100 strain, M. abscessus subsp. bolletii CRM
      0020, isolated from a patient in Rio de Janeiro, Brazil. 

PMID- 23950126
TI  - Draft genome sequences for three mercury-methylating, sulfate-reducing bacteria.
AB  - The genetic basis for bacterial mercury methylation has been described recently.
      For insights into the physiology of mercury-methylating bacteria, we present
      genome sequences for Desulfococcus multivorans strain DSM 2059, Desulfovibrio
      alkalitolerans strain DSM 16529, and Desulfovibrio species strain X2. 

PMID- 23950127
TI  - Complete Genome Sequence of an MLB2 Astrovirus from a Turkish Child with
      Diarrhea.
AB  - Only two complete genome sequences of MLB2 astroviruses are available, one from
      an Indian child with diarrhea and another from plasma of an American child. Here
      we report the complete MLB2 genome sequence from a Turkish child with diarrhea.
      This MLB2 astrovirus genome sequence shows high nucleotide identity with the
      American MLB2. 

PMID- 23950129
TI  - Draft Genome Sequence of Lactobacillus rhamnosus CRL1505, an Immunobiotic Strain
      Used in Social Food Programs in Argentina.
AB  - We report the draft genome sequence of the probiotic Lactobacillus rhamnosus
      strain CRL1505. This new probiotic strain has been included into official
      Nutritional Programs in Argentina. The draft genome sequence is composed of
      3,417,633 bp with 3,327 coding sequences. 

PMID- 23950128
TI  - Genome Sequence of Lysinibacillus sphaericus Strain KCTC 3346T.
AB  - Lysinibacillus sphaericus is a heterogeneous species that includes strains that
      produce mosquitocidal toxin proteins. Herein, we report the 4.56-Mb draft genome
      sequence of the nonpathogenic L. sphaericus strain KCTC 3346(T), which provides
      clues for the phylogenetic reassessment of L. sphaericus species and an
      understanding of its physiological properties. 

PMID- 23950130
TI  - Genome Sequence of the Autotrophic Acetogen Clostridium autoethanogenum JA1-1
      Strain DSM 10061, a Producer of Ethanol from Carbon Monoxide.
AB  - Clostridium autoethanogenum is an anaerobic, autotrophic acetogen that is capable
      of converting CO and CO2 into ethanol and acetate. Here we report the draft
      genome sequence of C. autoethanogenum JA1-1 strain DSM 10061 (4.5 Mbp; G+C
      content, 37.5%) and the findings obtained from annotation of the genome sequence.

PMID- 23950131
TI  - Comparative Genomic Analysis of Acheta domesticus Densovirus Isolates from
      Different Outbreaks in Europe, North America, and Japan.
AB  - The first densovirus from a cricket, Acheta domesticus densovirus (AdDNV)
      (Parvoviridae), was isolated in Europe in 1977 and has been studied previously.
      We compared seven additional AdDNV genomes isolated from 4 other European
      outbreaks, 2 major North American outbreaks, and a Japanese outbreak.
      Phylogenetic analysis suggested that the 2009 Japanese and North American
      outbreaks were not related. 

PMID- 23950132
TI  - Draft Genome Sequence of Winogradskyella psychrotolerans RS-3T, Isolated from the
      Marine Transect of Kongsfjorden, Ny-Alesund, Svalbard, Arctic Ocean.
AB  - The 4.3-Mb genome of Winogradskyella psychrotolerans strain RS-3(T), isolated
      from a sediment sample of a marine transect of Kongsfjorden, Ny-Alesund,
      Svalbard, Arctic Ocean, is reported. 

PMID- 23950133
TI  - Draft Genome Sequence of Salmonella enterica subsp. enterica Serovar Manhattan
      Strain 111113, from an Outbreak of Human Infections in Northern Italy.
AB  - We announce the draft genome sequence of Salmonella enterica subsp. enterica
      serovar Manhattan strain 111113, isolated from a patient during an outbreak in
      northern Italy. The genome, which was obtained with Illumina MiSeq technology, is
      composed of 21 contigs for a total of 4,684,342 bp, with a G+C content of 52.17%.

PMID- 23950134
TI  - Draft Genome Sequence of Leifsonia rubra Strain CMS 76RT, Isolated from a
      Cyanobacterial Mat Sample from a Pond in Wright Valley, McMurdo, Antarctica.
AB  - The 2.7-Mb draft genome sequence of Leifsonia rubra strain CMS 76R(T), isolated
      from a cyanobacterial mat sample from a pond in Wright Valley, McMurdo,
      Antarctica, is reported. 

PMID- 23950135
TI  - Draft Genome Sequence of Geobacillus kaustophilus GBlys, a Lysogenic Strain with
      Bacteriophage OH2.
AB  - Geobacillus kaustophilus strain GBlys was isolated along with the bacteriophage
      OH2, which infects G. kaustophilus NBRC 102445(T). Here we present a draft
      sequence of this strain's genome, which consists of 216 contigs for a total of
      3,541,481 bp, 3,679 predicted coding sequences, and a G+C content of 52.1%. 

PMID- 23950136
TI  - Genome Sequence of a Reassortant H5N1 Avian Influenza Virus Isolated from
      Domestic Green-Winged Teal.
AB  - An avian influenza virus strain, A/domestic green-winged
      teal/Hunan/3450/2006(H5N1) (DGW-T3450), was isolated from domestic green-winged
      teals. Genome analysis demonstrated that DGW-T3450 is a novel reassortant strain.
      The hemagglutinin (HA) and neuraminidase (NA) genes of this strain originated
      from H5N1 viruses circulating in poultry, while its remaining genes are derived
      from multiple ancestors, including viruses like those that infect wild birds. 

PMID- 23950137
TI  - Genome Sequence of the Probiotic Strain Lactobacillus rhamnosus (Formerly
      Lactobacillus casei) LOCK900.
AB  - Lactobacillus rhamnosus LOCK900 fulfills the criteria required for probiotic
      strains. In this study, we report a whole-genome sequence of this isolate and
      compare it with other L. rhamnosus complete genome sequences already published. 

PMID- 23950138
TI  - Draft Genome Sequence of Cyclobacterium qasimii Strain M12-11BT, Isolated from
      Arctic Marine Sediment.
AB  - A 6.29-Mb genome sequence of Cyclobacterium qasimii strain M12-11B(T), isolated
      from an Arctic marine sediment sample, is reported. 

PMID- 23950139
TI  - Recombinant lectin-like domain of thrombomodulin suppresses vascular inflammation
      by reducing leukocyte recruitment via interacting with Lewis Y on endothelial
      cells.
AB  - OBJECTIVE: The N-terminal lectin-like domain (domain 1 [D1]) of thrombomodulin
      (TM) is known to have an anti-inflammatory function. We previously showed that
      recombinant TM domain 1 (rTMD1) interacts with a carbohydrate molecule, Lewis Y
      (Le(y)), which is found to be expressed on adhesion molecules and involved in
      cell adhesion. Here, we tested the effect of rTMD1/Le(y) interaction on leukocyte
      recruitment in inflammation. APPROACH AND RESULTS: The expression of Le(y) on the
      surface of human umbilical vein endothelial cells was increased by tumor necrosis
      factor-alpha stimulation. Direct binding of rTMD1 to Le(y) on the cell surface
      was observed. rTMD1 inhibited Le(y)-mediated leukocyte adhesion on the Le(y)
      immobilized flow chamber and activated endothelium under a shear flow. The
      following leukocyte transmigration to endothelium was also reduced by rTMD1
      through binding Le(y). In vivo, treatment of rTMD1 reduced leukocyte recruitment
      to the inflammatory sites in carotid ligation injury and thioglycollate-induced
      peritonitis. rTMD1 administration in apolipoprotein E-deficient mice effectively
      suppressed atherosclerotic plaque formation and macrophage infiltration in
      atherosclerotic lesions. Increased Le(y) expression, as well as administered
      rTMD1, was observed in inflamed vessels. CONCLUSIONS: rTMD1 suppresses vascular
      inflammation by inhibiting leukocyte recruitment to endothelium through
      attenuating Le(y)-mediated adhesion and further protects against atherosclerosis
      progression. The present study provides a mechanism showing that rTMD1 can
      inhibit inflammation by binding to its carbohydrate ligand Le(y).

PMID- 23950140
TI  - Maternal hypercholesterolemia in pregnancy associates with umbilical vein
      endothelial dysfunction: role of endothelial nitric oxide synthase and arginase
      II.
AB  - OBJECTIVE: Human pregnancy that courses with maternal supraphysiological
      hypercholesterolemia (MSPH) correlates with atherosclerotic lesions in fetal
      arteries. It is known that hypercholesterolemia associates with endothelial
      dysfunction in adults, a phenomenon where nitric oxide (NO) and arginase are
      involved. However, nothing is reported on potential alterations in the
      fetoplacental endothelial function in MSPH. The aim of this study was to
      determine whether MSPH alters fetal vascular reactivity via endothelial
      arginase/urea and L-arginine transport/NO signaling pathways. APPROACH AND
      RESULTS: Total cholesterol <280 mg/dL was considered as maternal physiological
      hypercholesterolemia (n=46 women) and >= 280 mg/dL as MSPH (n=28 women). Maternal
      but not fetal total cholesterol and low-density lipoprotein-cholesterol levels
      were elevated in MSPH. Umbilical veins were used for vascular reactivity assays
      (wire myography), and primary cultures of umbilical vein endothelial cells to
      determine arginase, endothelial NO synthase (eNOS), and human cationic amino acid
      transporter 1 and human cationic amino acid transporter 2A/B expression and
      activity. MSPH reduced calcitonine gene-related peptide-umbilical vein relaxation
      and increased intima/media ratio (histochemistry), as well as reduced eNOS
      activity (L-citrulline synthesis from L-arginine, eNOS
      phosphorylation/dephosphorylation), but increased arginase activity and arginase
      II protein abundance. Arginase inhibition increased eNOS activity and L-arginine
      transport capacity without altering human cationic amino acid transporter 1 or
      human cationic amino acid transporter 2A/B protein abundance in maternal
      physiological hypercholesterolemia and MSPH. CONCLUSIONS: MSPH is a
      pathophysiological condition altering umbilical vein reactivity because of fetal
      endothelial dysfunction associated with arginase and eNOS signaling imbalance. We
      speculate that elevated maternal circulating cholesterol is a factor leading to
      fetal endothelial dysfunction, which could have serious consequences to the
      growing fetus.

PMID- 23950141
TI  - Overexpression of catalase in vascular smooth muscle cells prevents the formation
      of abdominal aortic aneurysms.
AB  - OBJECTIVE: Elevated levels of oxidative stress have been reported in abdominal
      aortic aneurysms (AAA), but which reactive oxygen species promotes the
      development of AAA remains unclear. Here, we investigate the effect of hydrogen
      peroxide (H2O2)-degrading enzyme catalase on the formation of AAA. APPROACH AND
      RESULTS: AAA were induced with the application of calcium chloride (CaCl2) on
      mouse infrarenal aortas. The administration of PEG-catalase, but not saline,
      attenuated the loss of tunica media and protected against AAA formation (0.91 +/-
      0.1 versus 0.76 +/- 0.09 mm). Similarly, in a transgenic mouse model, catalase
      overexpression in the vascular smooth muscle cells preserved the thickness of
      tunica media and inhibited aortic dilatation by 50% (0.85 +/- 0.14 versus 0.57 +/
      0.08 mm). Further studies showed that injury with CaCl2 decreased catalase
      expression and activity in the aortic wall. Pharmacological administration or
      genetic overexpression of catalase restored catalase activity and subsequently
      decreased matrix metalloproteinase activity. In addition, a profound reduction in
      inflammatory markers and vascular smooth muscle cell apoptosis was evident in
      aortas of catalase-overexpressing mice. Interestingly, as opposed to infusion of
      PEG-catalase, chronic overexpression of catalase in vascular smooth muscle cells
      did not alter the total aortic H2O2 levels. CONCLUSIONS: The data suggest that a
      reduction in aortic wall catalase activity can predispose to AAA formation.
      Restoration of catalase activity in the vascular wall enhances aortic vascular
      smooth muscle cell survival and prevents AAA formation primarily through
      modulation of matrix metalloproteinase activity.

PMID- 23950142
TI  - Immunosuppressive drug azathioprine reduces aneurysm progression through
      inhibition of Rac1 and c-Jun-terminal-N-kinase in endothelial cells.
AB  - OBJECTIVE: In aortic aneurysms the arterial vessel wall is dilated because of
      destruction of its integrity, which may lead to lethal vessel rupture. Chronic
      infiltration of inflammatory cells into the vessel wall is fundamental to
      aneurysm pathology. We aim to limit aneurysm growth by inhibition of inflammation
      and reducing endothelial cell (EC) activation with immunosuppressive drug
      azathioprine (Aza). APPROACH AND RESULTS: Aza and its metabolite 6-mercaptopurine
      have anti-inflammatory effects on leukocytes. We here demonstrate that treatment
      of ECs with 6-mercaptopurine inhibits cell activation as illustrated by reduced
      expression of interleukin-12, CCL5, CCL2, and vascular cell adhesion molecule-1
      and inhibition of monocyte-EC adhesion. The underlying mechanism of 6
      mercaptopurine involves suppression of GTPase Rac1 activation, resulting in
      reduced phosphorylation of c-Jun-terminal-N-kinase and c-Jun. Subsequently, the
      effect of Aza was investigated in aneurysm formation in the angiotensin II
      aneurysm mouse model in apolipoprotein E-deficient mice. We demonstrated that Aza
      decreases de novo aortic aneurysm formation from an average aneurysm severity
      score of 2.1 (control group) to 0.6 (Aza group), and that Aza effectively delays
      aorta pathology in a progression experiment, resulting in a reduced severity
      score from 2.8 to 1.7 in Aza-treated mice. In line with the in vitro
      observations, Aza-treated mice showed less c-Jun-terminal-N-kinase activation in
      ECs and reduced leukocyte influx in the aortic wall. CONCLUSIONS: The
      immunosuppressive drug Aza has an anti-inflammatory effect and in ECs inhibits
      Rac1 and c-Jun-terminal-N-kinase activation, which may explain the protective
      effect of Aza in aneurysm development and, most importantly for clinical
      implications, aneurysm severity.

PMID- 23950143
TI  - Attenuation of experimental atherosclerosis by interleukin-19.
AB  - OBJECTIVE: Interleukin-19 (IL-19) is a putative Th2, anti-inflammatory
      interleukin. Its expression and potential role in atherogenesis are unknown. IL
      19 is not detected in normal artery and is expressed to a greater degree in
      plaque from symptomatic versus asymptomatic patients, suggesting a compensatory
      counter-regulatory function. We tested whether IL-19 could reduce atherosclerosis
      in susceptible mice and identified plausible mechanisms. APPROACH AND RESULTS:
      LDLR(-/-) mice fed an atherogenic diet and injected with either 1.0 or 10.0 ng/g
      per day recombinant mouse IL-19 had significantly less plaque area in the aortic
      arch compared with controls (P<0.0001). Weight gain, cholesterol, and
      triglyceride levels were not significantly different. Gene expression in
      splenocytes from IL-19-treated mice demonstrated immune cell Th2 polarization,
      with decreased expression of T-bet, interferon-gamma, interleukin-1beta, and
      interleukin-12beta and increased expression of GATA3 and FoxP3 mRNA. A greater
      percentage of lymphocytes were Th2 polarized in IL-19-treated mice. Cellular
      characterization of plaque by immunohistochemistry demonstrated that IL-19
      treated mice have significantly less macrophage infiltrate compared with controls
      (P<0.001). Intravital microscopy revealed significantly less leukocyte adhesion
      in wild-type mice injected with IL-19 and fed an atherogenic diet compared with
      controls. Treatment of cultured endothelial cells, vascular smooth muscle cells,
      and bone marrow-derived macrophages with IL-19 resulted in a significant decrease
      in chemokine mRNA and mRNA stability protein human antigen R. CONCLUSIONS: These
      data suggest that IL-19 is a potent inhibitor of experimental atherosclerosis,
      with diverse mechanisms including immune cell polarization, decrease in
      macrophage adhesion, and decrease in gene expression. This may identify IL-19 as
      a novel therapeutic to limit vascular inflammation.

PMID- 23950144
TI  - Endothelial G protein-coupled receptor kinase 2 regulates vascular homeostasis
      through the control of free radical oxygen species.
AB  - OBJECTIVE: The role of endothelial G protein-coupled receptor kinase 2 (GRK2) was
      investigated in mice with selective deletion of the kinase in the endothelium
      (Tie2-CRE/GRK2(fl/fl)). APPROACH AND RESULTS: Aortas from Tie2-CRE/GRK2(fl/fl)
      presented functional and structural alterations as compared with control
      GRK2(fl/fl) mice. In particular, vasoconstriction was blunted to different
      agonists, and collagen and elastic rearrangement and macrophage infiltration were
      observed. In primary cultured endothelial cells deficient for GRK2, mitochondrial
      reactive oxygen species was increased, leading to expression of cytokines.
      Chronic treatment with a reactive oxygen species scavenger in mice corrected the
      vascular phenotype by recovering vasoconstriction, structural abnormalities, and
      reducing macrophage infiltration. CONCLUSIONS: These results demonstrate that
      GRK2 removal compromises vascular phenotype and integrity by increasing
      endothelial reactive oxygen species production.

PMID- 23950145
TI  - Defining cell-type specificity at the transcriptional level in human disease.
AB  - Cell-lineage-specific transcripts are essential for differentiated tissue
      function, implicated in hereditary organ failure, and mediate acquired chronic
      diseases. However, experimental identification of cell-lineage-specific genes in
      a genome-scale manner is infeasible for most solid human tissues. We developed
      the first genome-scale method to identify genes with cell-lineage-specific
      expression, even in lineages not separable by experimental microdissection. Our
      machine-learning-based approach leverages high-throughput data from tissue
      homogenates in a novel iterative statistical framework. We applied this method to
      chronic kidney disease and identified transcripts specific to podocytes, key
      cells in the glomerular filter responsible for hereditary and most acquired
      glomerular kidney disease. In a systematic evaluation of our predictions by
      immunohistochemistry, our in silico approach was significantly more accurate (65%
      accuracy in human) than predictions based on direct measurement of in vivo
      fluorescence-tagged murine podocytes (23%). Our method identified genes
      implicated as causal in hereditary glomerular disease and involved in molecular
      pathways of acquired and chronic renal diseases. Furthermore, based on expression
      analysis of human kidney disease biopsies, we demonstrated that expression of the
      podocyte genes identified by our approach is significantly related to the degree
      of renal impairment in patients. Our approach is broadly applicable to define
      lineage specificity in both cell physiology and human disease contexts. We
      provide a user-friendly website that enables researchers to apply this method to
      any cell-lineage or tissue of interest. Identified cell-lineage-specific
      transcripts are expected to play essential tissue-specific roles in organogenesis
      and disease and can provide starting points for the development of organ-specific
      diagnostics and therapies. 

PMID- 23950147
TI  - Estimating inbreeding coefficients from NGS data: Impact on genotype calling and
      allele frequency estimation.
AB  - Most methods for next-generation sequencing (NGS) data analyses incorporate
      information regarding allele frequencies using the assumption of Hardy-Weinberg
      equilibrium (HWE) as a prior. However, many organisms including those that are
      domesticated, partially selfing, or with asexual life cycles show strong
      deviations from HWE. For such species, and specially for low-coverage data, it is
      necessary to obtain estimates of inbreeding coefficients (F) for each individual
      before calling genotypes. Here, we present two methods for estimating inbreeding
      coefficients from NGS data based on an expectation-maximization (EM) algorithm.
      We assess the impact of taking inbreeding into account when calling genotypes or
      estimating the site frequency spectrum (SFS), and demonstrate a marked increase
      in accuracy on low-coverage highly inbred samples. We demonstrate the
      applicability and efficacy of these methods in both simulated and real data sets.

PMID- 23950146
TI  - Inferring gene expression from ribosomal promoter sequences, a crowdsourcing
      approach.
AB  - The Gene Promoter Expression Prediction challenge consisted of predicting gene
      expression from promoter sequences in a previously unknown experimentally
      generated data set. The challenge was presented to the community in the framework
      of the sixth Dialogue for Reverse Engineering Assessments and Methods (DREAM6), a
      community effort to evaluate the status of systems biology modeling
      methodologies. Nucleotide-specific promoter activity was obtained by measuring
      fluorescence from promoter sequences fused upstream of a gene for yellow
      fluorescence protein and inserted in the same genomic site of yeast Saccharomyces
      cerevisiae. Twenty-one teams submitted results predicting the expression levels
      of 53 different promoters from yeast ribosomal protein genes. Analysis of
      participant predictions shows that accurate values for low-expressed and mutated
      promoters were difficult to obtain, although in the latter case, only when the
      mutation induced a large change in promoter activity compared to the wild-type
      sequence. As in previous DREAM challenges, we found that aggregation of
      participant predictions provided robust results, but did not fare better than the
      three best algorithms. Finally, this study not only provides a benchmark for the
      assessment of methods predicting activity of a specific set of promoters from
      their sequence, but it also shows that the top performing algorithm, which used
      machine-learning approaches, can be improved by the addition of biological
      features such as transcription factor binding sites. 

PMID- 23950149
TI  - Kallotenue papyrolyticum gen. nov., sp. nov., a cellulolytic and filamentous
      thermophile that represents a novel lineage (Kallotenuales ord. nov.,
      Kallotenuaceae fam. nov.) within the class Chloroflexia.
AB  - Several closely related, thermophilic and cellulolytic bacterial strains,
      designated JKG1(T), JKG2, JKG3, JKG4 and JKG5, were isolated from a cellulolytic
      enrichment (corn stover) incubated in the water column of Great Boiling Spring,
      NV. Strain JKG1(T) had cells of diameter 0.7-0.9 um and length ~2.0 um that
      formed non-branched, multicellular filaments reaching >300 um. Spores were not
      formed and dense liquid cultures were red. The temperature range for growth was
      45-65  degrees C, with an optimum of 55  degrees C. The pH range for growth was
      pH 5.6-9.0, with an optimum of pH 7.5. JKG1(T) grew as an aerobic heterotroph,
      utilizing glucose, sucrose, xylose, arabinose, cellobiose, CM-cellulose, filter
      paper, microcrystalline cellulose, xylan, starch, Casamino acids, tryptone,
      peptone, yeast extract, acetate, citrate, lactate, pyruvate and glycerol as sole
      carbon sources, and was not observed to photosynthesize. The cells stained Gram
      negative. Phylogenetic analysis using 16S rRNA gene sequences placed the new
      isolates in the class Chloroflexia, but distant from other cultivated members,
      with the highest sequence identity of 82.5 % to Roseiflexus castenholzii. The
      major quinone was menaquinone-9; no ubiquinones were detected. The major cellular
      fatty acids (>5 %) were C18 : 0, anteiso-C17 : 0, iso-C18 : 0, iso-C17 : 0, C16 :
      0, iso-C16 : 0 and C17 : 0. The peptidoglycan amino acids were alanine,
      ornithine, glutamic acid, serine and asparagine. Whole-cell sugars included
      mannose, rhamnose, glucose, galactose, ribose, arabinose and xylose.
      Morphological, phylogenetic and chemotaxonomic results suggest that JKG1(T) is
      representative of a new lineage within the class Chloroflexia, which we propose
      to designate Kallotenue papyrolyticum gen. nov., sp. nov., Kallotenuaceae fam.
      nov., Kallotenuales ord. nov. The type strain of Kallotenue papyrolyticum gen.
      nov., sp. nov. is JKG1(T) ( = DSM 26889(T) = JCM 19132(T)). 

PMID- 23950148
TI  - Acinetobacter kookii sp. nov., isolated from soil.
AB  - Two Gram-stain-negative, non-fermentative bacterial strains, designated 11
      0202(T) and 11-0607, were isolated from soil in South Korea, and four others, LUH
      13522, LUH 8638, LUH 10268 and LUH 10288, were isolated from a beet field in
      Germany, soil in the Netherlands, and sediment of integrated fish farms in
      Malaysia and Thailand, respectively. Based on 16S rRNA, rpoB and gyrB gene
      sequences, they are considered to represent a novel species of the genus
      Acinetobacter. Their 16S rRNA gene sequences showed greatest pairwise similarity
      to Acinetobacter beijerinckii NIPH 838(T) (97.9-98.4 %). They shared highest rpoB
      and gyrB gene sequence similarity with Acinetobacter johnsonii DSM 6963(T) and
      Acinetobacter bouvetii 4B02(T) (85.4-87.6 and 78.1-82.7 %, respectively). Strain
      11-0202(T) displayed low DNA-DNA reassociation values (<40 %) with the most
      closely related species of the genus Acinetobacter. The six strains utilized
      azelate, 2,3-butanediol, ethanol and dl-lactate as sole carbon sources. Cellular
      fatty acid analyses showed similarities to profiles of related species of the
      genus Acinetobacter: summed feature 3 (C16 : 1omega7c, C16 : 1omega6c; 24.3-27.2
      %), C18 : 1omega9c (19.9-22.1 %), C16 : 0 (15.2-22.0 %) and C12 : 0 (9.2-14.2 %).
      On the basis of the current findings, it is concluded that the six strains
      represent a novel species, for which the name Acinetobacter kookii sp. nov. is
      proposed. The type strain is 11-0202(T) ( = KCTC 32033(T) = JCM 18512(T)). 

PMID- 23950150
TI  - Shewanella aestuarii sp. nov., a marine bacterium isolated from a tidal flat.
AB  - A Gram-stain-negative, non-spore-forming, facultatively anaerobic bacterium,
      designated strain SC18(T), was isolated from a tidal flat of Suncheon bay in
      South Korea. Cells were rod-shaped and motile by means of a polar flagellum.
      Cells were catalase-, oxidase- and beta-haemolysis-positive. Growth was observed
      at 4-37  degrees C (optimum, 25-30  degrees C), at pH 5.0-9.0 (optimum, pH 7.0)
      and in the presence of 0-5.0 % (w/v) NaCl (optimum, 0-2 %). The major cellular
      fatty acids were summed feature 3 (comprising C16 : 1omega7c and/or C16 :
      1omega6c), iso-C15 : 0 and C16 : 0. The polar lipid pattern indicated the
      presence of phosphatidylethanolamine, phosphatidylglycerol,
      phosphatidylmethylethanolamine, an unidentified aminolipid and three unidentified
      lipids. Strain SC18(T) contained Q-7, Q-8, MK-7 and MMK-7 as the dominant
      respiratory quinones and the G+C content of the genomic DNA was 41.3 mol%.
      Phylogenetic analysis based on 16S rRNA and gyrase B (gyrB) gene sequences showed
      that strain SC18(T) formed a tight phyletic lineage with members of the genus
      Shewanella. Strain SC18(T) was related most closely to Shewanella denitrificans
      OS217(T) (97.3 % 16S rRNA gene sequence similarity) and Shewanella gaetbuli TF
      27(T) (97.1 %), but the DNA-DNA relatedness levels between strain SC18(T) and the
      type strains of S. denitrificans and S. gaetbuli were 18.3+/-2.8 and 22.5+/-1.6 %
      (mean+/-sd), respectively. On the basis of phenotypic, chemotaxonomic and
      molecular features, strain SC18(T) represents a novel species of the genus
      Shewanella, for which the name Shewanella aestuarii sp. nov. is proposed. The
      type strain is SC18(T) ( = KACC 16187(T) = JCM 17801(T)). 

PMID- 23950151
TI  - Lactobacillus mudanjiangensis sp. nov., Lactobacillus songhuajiangensis sp. nov.
      and Lactobacillus nenjiangensis sp. nov., isolated from Chinese traditional
      pickle and sourdough.
AB  - Three Gram-stain-positive bacterial strains, 11050(T), 7-19(T) and 11102(T), were
      isolated from traditional pickle and sourdough in Heilongjiang Province, China.
      These bacteria were characterized by a polyphasic approach, including 16S rRNA
      gene sequence analysis, pheS gene sequence analysis, rpoA gene sequence analysis,
      dnaK gene sequence analysis, fatty acid methyl ester (FAME) analysis,
      determination of DNA G+C content, DNA-DNA hybridization and an analysis of
      phenotypic features. Strain 11050(T) belonged to the Lactobacillus plantarum
      species group and shared 98.0-98.4 % 16S rRNA gene sequence similarities and 84.7
      88.9 % dnaK gene sequence similarities with type strains of Lactobacillus
      plantarum subsp. plantarum, Lactobacillus plantarum subsp. argentoratensis,
      Lactobacillus pentosus, Lactobacillus paraplantarum, Lactobacillus fabifermentans
      and Lactobacillus xiangfangensis and had 75.9-80.7 % pheS gene sequence
      similarities and 90.7-92.5 % rpoA gene sequence similarities with Lactobacillus
      plantarum subsp. plantarum LMG 6907(T), Lactobacillus plantarum subsp.
      argentoratensis LMG 9205, Lactobacillus pentosus LMG 10755(T), Lactobacillus
      paraplantarum LMG 16673(T), Lactobacillus fabifermentans LMG 24284(T) and
      Lactobacillus xiangfangensis 3.1.1(T), respectively. Strain 7-19(T) was
      phylogenetically related to Lactobacillus thailandensis, Lactobacillus pantheris
      and Lactobacillus sharpeae, having 94.1-96.7 % 16S rRNA gene sequence
      similarities, 71.5-82.3 % pheS gene sequence similarities and 71.2-83.4 % rpoA
      gene sequence similarities with type strains of Lactobacillus thailandensis,
      Lactobacillus pantheris and Lactobacillus sharpeae, respectively. Strain 11102(T)
      was phylogenetically related to Lactobacillus oligofermentans, Lactobacillus
      suebicus, Lactobacillus vaccinostercus and Lactobacillus hokkaidonensis. Strain
      11102(T) had 99.2 % 16S rRNA gene sequence similarity, 81.3 % pheS gene sequence
      similarity and 96.1 % rpoA gene sequence similarity with Lactobacillus
      oligofermentans LMG 22743(T), respectively. Strain 11102(T) shared 96.0-96.8 %
      16S rRNA gene sequence similarities, 73.3-81.0 % pheS gene sequence similarities
      and 74.6-76.9 % rpoA gene sequence similarities with type strains of
      Lactobacillus suebicus, Lactobacillus vaccinostercus and Lactobacillus
      hokkaidonensis, respectively. Based upon the data from polyphasic
      characterization obtained in the present study, three novel species,
      Lactobacillus mudanjiangensis sp. nov., Lactobacillus songhuajiangensis sp. nov.
      and Lactobacillus nenjiangensis sp. nov., are proposed and the type strains are
      11050(T) ( = LMG 27194(T) = CCUG 62991(T)), 7-19(T) ( = LMG 27191(T) = NCIMB
      14832(T) = CCUG 62990(T)) and 11102(T) ( = LMG 27192(T) = NCIMB 14833(T)),
      respectively. 

PMID- 23950153
TI  - Inhibition of miR-205 impairs the wound-healing process in human corneal
      epithelial cells by targeting KIR4.1 (KCNJ10).
AB  - PURPOSE: The aim of the study was to test the hypotheses that injury stimulates
      the expression of miR-205, which in turn inhibits KCNJ10 channels by targeting
      its 3' UTR, thereby facilitating the wound-healing process in human corneal
      epithelial cells (HCECs). METHODS: A stem-loop qRT-PCR was used to examine the
      miR-205 expression. BrdU cell proliferation assay and wound scratch assay were
      applied to measure the effect of miR-205 mimic or antagomer in HCECs. The patch
      clamp technique, dual luciferase reporter assay, and Western blot analysis were
      employed to test whether miR-205 regulates KCNJ10, one of the target genes of miR
      205. Both of the primary human and mouse corneal epithelial cells (pH/MCECs) were
      employed to further confirm the observations obtained in HCECs. RESULTS: The
      scratch injury in pH/MCECs increased the expression of miR-205 and decreased the
      expression of KCNJ10 within 24 hours. The notion that miR-205 may target KCNJ10
      was supported by dual luciferase reporter assay showing an inhibition effect of
      miR-205 on 3' UTR of KCNJ10. Application of miR-205 antagomer significantly
      delayed the regrowth in wounded HCECs. However, inhibition of KCNJ10 partially
      abolished the effect from miR-205 antagomer and restored the healing process.
      Moreover, overexpression miR-205 antagomer enhanced the protein expression of
      KCNJ10 but not KCNJ16. In addition, patch-clamp demonstrated that inhibition of
      endogenous miR-205 expression increased Ba2+-sensitive inwardly rectifying K+
      channels. In addition, an electrophysiological study of pHCECs showed the
      presence of KCNJ10-like 20 pS K+ channels and scratch injury significantly
      decreased the Ba2+-sensitive inwardly rectifying K+ currents. CONCLUSIONS: miR
      205 stimulates wound healing by inhibiting its target gene KCNJ10.

PMID- 23950152
TI  - Prevalence of mutations in eyeGENE probands with a diagnosis of autosomal
      dominant retinitis pigmentosa.
AB  - PURPOSE: To screen samples from patients with presumed autosomal dominant
      retinitis pigmentosa (adRP) for mutations in 12 disease genes as a contribution
      to the research and treatment goals of the National Ophthalmic Disease Genotyping
      and Phenotyping Network (eyeGENE). METHODS: DNA samples were obtained from
      eyeGENE. A total of 170 probands with an intake diagnosis of adRP were tested
      through enrollment in eyeGENE. The 10 most common genes causing adRP (IMPDH1,
      KLHL7, NR2E3, PRPF3/RP18, PRPF31/RP11, PRPF8/RP13, PRPH2/RDS, RHO, RP1, and
      TOPORS) were chosen for PCR-based dideoxy sequencing, along with the two X-linked
      RP genes, RPGR and RP2. RHO, PRPH2, PRPF31, RPGR, and RP2 were completely
      sequenced, while only mutation hotspots in the other genes were analyzed.
      RESULTS: Disease-causing mutations were identified in 52% of the probands. The
      frequencies of disease-causing mutations in the 12 genes were consistent with
      previous studies. CONCLUSIONS: The Laboratory for Molecular Diagnosis of
      Inherited Eye Disease at the University of Texas in Houston has thus far received
      DNA samples from 170 families with a diagnosis of adRP from the eyeGENE Network.
      Disease-causing mutations in autosomal genes were identified in 48% (81/170) of
      these families while mutations in X-linked genes accounted for an additional 4%
      (7/170). Of the 55 distinct mutations detected, 19 (33%) have not been previously
      reported. All diagnostic results were returned by eyeGENE to participating
      patients via their referring clinician. These genotyped samples along with their
      corresponding phenotypic information are also available to researchers who may
      request access to them for further study of these ophthalmic disorders.
      (ClinicalTrials.gov number, NCT00378742.).

PMID- 23950154
TI  - Heritability of refractive astigmatism: a population-based twin study among 63-
      to 75-year-old female twins.
AB  - PURPOSE: To examine the heritability of refractive astigmatism in older women.
      METHODS: Astigmatism was measured with an autorefractor in 88 monozygotic and 82
      dizygotic female twin pairs aged 63 to 75 years. The prevalence and distribution
      of astigmatism and polar values J0 and J45 were estimated by standard statistical
      methods. Bivariate maximum likelihood model fitting was used to estimate genetic
      and environmental variance components using information from both eyes. RESULTS:
      Mean astigmatism of the more astigmatic eye was 0.93 diopters (D; SD +/-0.58).
      Astigmatism of at least 0.25 D, 0.5 D, 0.75 D, or 1.0 D in either eye was present
      in 99.7%, 88.5%, 66.5%, and 46.2% of cases, respectively. The main direction of
      astigmatism was against the rule. The age-adjusted quantitative genetic modeling
      revealed that additive genetic effects accounted for 33.3% (95% confidence
      interval [CI], 21.9%-43.8%) of the total variance of astigmatism and for 18% (95%
      CI, 4%-31%) of the total variance of polar value J45 of both eyes (bivariate
      model), with the remaining variances due to nongenetic effects. There were no
      significant correlations between the twin pairs for polar value J0. CONCLUSIONS:
      In elderly female twins, additive genetic effects accounted for one-third of the
      variance of the amount of astigmatism and only a small fraction of the total
      variance of polar value J45.

PMID- 23950155
TI  - Association between the cholesteryl ester transfer protein gene and polypoidal
      choroidal vasculopathy.
AB  - PURPOSE: To determine whether genetic variants in the lipid-associated genes are
      related to the risk of developing polypoidal choroidal vasculopathy (PCV) in a
      Japanese population. METHODS: Five hundred eighty-one patients with PCV and 793
      controls were enrolled in the study. Association analysis of allele and genotype
      frequencies was performed for the following single-nucleotide polymorphisms
      (SNPs) that are associated with high-density lipoprotein cholesterol levels in
      blood: rs493258 at the hepatic lipase gene (LIPC), rs3764261 at the cholesteryl
      ester transfer protein gene (CETP), and rs12678919 at the lipoprotein lipase gene
      (LPL). A further model adjusting for age-related maculopathy susceptibility 2
      (ARMS2) A69S, complement factor H (CFH) I62V, age, sex, and smoking status was
      used to confirm the independent association of these SNPs with other covariates.
      RESULTS: CETP rs3764261 was significantly associated with the development of PCV;
      the frequency of the minor allele A was higher in the PCV cases (24.0%) than in
      the control subjects (18.5%) (P = 0.0025; odds ratio [OR], 1.41; 95% confidence
      interval, 1.13-1.75). Furthermore, we found an independent association of CETP
      variants with age, sex, smoking status, and genetic background of ARMS2 A69S, CFH
      I62V, LIPC rs493258, and LPL rs12678919 (P = 0.0013; OR, 1.50). LIPC rs493258 and
      LPL rs12678919 did not show significant associations with the development of PCV
      (P > 0.05). CONCLUSION: CETP variants are associated a risk of developing PCV
      among the Japanese population.

PMID- 23950156
TI  - Hypotensive effect of latanoprost/timolol versus travoprost/timolol fixed
      combinations in NTG patients: a randomized, multicenter, crossover clinical
      trial.
AB  - PURPOSE: To compare the ocular hypotensive effect of travoprost plus timolol
      (TTFC) and latanoprost plus timolol fixed combinations (LTFC) in patients with
      normal-tension glaucoma (NTG). METHODS: A two-sequence 12-week, multicenter,
      prospective, randomized, single-blinded, crossover clinical trial examined 59 NTG
      patients. If both eyes were eligible, only one eye (chosen at random) was used
      for analytical purposes. After a 12-week run-in period with dorzolamide plus
      timolol fixed combination (DTFC), patients were randomized into one of the two
      crossover sequences of treatment for 12 weeks with TTFC or LTFC and were
      subsequently crossed over to the alternative treatment for a further 12 weeks.
      The primary endpoint was reduction in IOP after 12 weeks of each treatment
      sequence. The effect of treatment on IOP was assessed using a linear mixed model.
      RESULTS: The mean baseline IOP was 14.8 +/- 3.3 mm Hg (95% confidence interval
      [CI], 14.1-15.3 mm Hg) for treatment with DTFC. The TTFC treatment period showed
      consistently lower mean IOP compared with LTFC treatment period at all
      measurement time points. Mean reduction in IOP at 12 weeks was significantly
      greater in the TTFC group than in the LTFC group (-2.4 +/- 2.3 mm Hg vs. -1.1 +/-
      2.3 mm Hg; P = 0.021). No interaction between the drug and treatment sequence was
      detected. The effects of intraocular lens implantation and measurement time were
      also not significant. The tolerability profiles of both treatments were similar.
      CONCLUSIONS: The additional reduction in IOP was greater with TTFC than with
      LTFC, and their tolerability profiles were similar. (http://www.umin.ac.jp/ctr/
      number, UMIN 000005974.).

PMID- 23950157
TI  - Perceptual learning in children with visual impairment improves near visual
      acuity.
AB  - PURPOSE: This study investigated whether visual perceptual learning can improve
      near visual acuity and reduce foveal crowding effects in four- to nine-year-old
      children with visual impairment. METHODS: Participants were 45 children with
      visual impairment and 29 children with normal vision. Children with visual
      impairment were divided into three groups: a magnifier group (n = 12), a crowded
      perceptual learning group (n = 18), and an uncrowded perceptual learning group (n
      = 15). Children with normal vision also were divided in three groups, but were
      measured only at baseline. Dependent variables were single near visual acuity
      (NVA), crowded NVA, LH line 50% crowding NVA, number of trials, accuracy,
      performance time, amount of small errors, and amount of large errors. Children
      with visual impairment trained during six weeks, two times per week, for 30
      minutes (12 training sessions). RESULTS: After training, children showed
      significant improvement of NVA in addition to specific improvements on the
      training task. The crowded perceptual learning group showed the largest acuity
      improvements (1.7 logMAR lines on the crowded chart, P < 0.001). Only the
      children in the crowded perceptual learning group showed improvements on all NVA
      charts. CONCLUSIONS: Children with visual impairment benefit from perceptual
      training. While task-specific improvements were observed in all training groups,
      transfer to crowded NVA was largest in the crowded perceptual learning group. To
      our knowledge, this is the first study to provide evidence for the improvement of
      NVA by perceptual learning in children with visual impairment.
      (http://www.trialregister.nl number, NTR2537.).

PMID- 23950158
TI  - Outcomes following fractured neck of femurin an Australian metropolitan teaching
      hospital.
AB  - OBJECTIVES: To determine the morbidity and mortality outcomes of patients
      presenting with a fractured neck of femur in an Australian context. Peri
      operative variables related to unfavourable outcomes were identified to allow
      planning of intervention strategies for improving peri-operative care. METHODS:
      We performed a retrospective observational study of 185 consecutive adult
      patients admitted to an Australian metropolitan teaching hospital with fractured
      neck of femur between 2009 and 2010. The main outcome measures were 30-day and
      one-year mortality rates, major complications and factors influencing mortality.
      RESULTS: The majority of patients were elderly, female and had multiple
      comorbidities. Multiple peri-operative medical complications were observed,
      including pre-operative hypoxia (17%), post-operative delirium (25%), anaemia
      requiring blood transfusion (28%), representation within 30 days of discharge
      (18%), congestive cardiac failure (14%), acute renal impairment (12%) and
      myocardial infarction (4%). Mortality rates were 8.1% at 30 days and 21.6% at one
      year. Factors predictive of one-year mortality were American Society of
      Anesthesiologists (ASA) score (odds ratio (OR) 4.2 (95% confidence interval (CI)
      1.5 to 12.2)), general anaesthesia (OR 3.1 (95% CI 1.1 to 8.5)), age > 90 years
      (OR 4.5 (95% CI 1.5 to 13.1)) and post-operative oliguria (OR 3.6 (95% CI 1.1 to
      11.7)). CONCLUSIONS: Results from an Australian metropolitan teaching hospital
      confirm the persistently high morbidity and mortality in patients presenting with
      a fractured neck of femur. Efforts should be aimed at medically optimising
      patients pre-operatively and correction of pre-operative hypoxia. This study
      provides planning data for future interventional studies. Cite this article: Bone
      Joint Res 2013;2:162-8.

PMID- 23950159
TI  - Rethinking A2E.

PMID- 23950160
TI  - Star spangled manner: astrocytes and neurons contribute to adenosine release in
      the hippocampus.

PMID- 23950161
TI  - Class warfare resolved in the auditory midbrain.

PMID- 23950162
TI  - Quite simple at first glance - complex at a second: modulating neuronal activity
      by tDCS.

PMID- 23950163
TI  - A contralateral repeated bout effect attenuates induction of NF-kappaB DNA
      binding following eccentric exercise.
AB  - We investigated the existence of contralateral repeated bout effect and tested if
      the attenuation of nuclear factor-kappa B (NF-kappaB; an important regulator of
      muscle inflammation) induction following eccentric exercise is a potential
      mechanism. Thirty-one healthy men performed two bouts of knee extension eccentric
      exercise, initially with one leg and then with the opposite leg 4 wk later.
      Vastus lateralis muscle biopsies of both exercised and control legs were taken 3
      h postexercise. Knee extension isometric and isokinetic strength (60 degrees /sec
      and 180 degrees /sec) were measured at baseline, pre-exercise, immediately
      postexercise, and 1/day for 5 days postexercise. Serum creatine kinase (CK)
      activity and muscle soreness were assessed at baseline and 1/day for 5 days
      postexercise. NF-kappaB (p65) DNA-binding activity was measured in the muscle
      biopsies. Isometric strength loss was lower in bout 2 than in bout 1 at 24, 72,
      and 96 h postexercise (P < 0.05). Isokinetic strength (60 degrees /s and 180
      degrees /s) was reduced less in bout 2 than in bout 1 at 72 h postexercise (P <
      0.01). There were no significant differences between bouts for postexercise CK
      activity or muscle soreness. p65 DNA-binding activity was increased following
      eccentric exercise (compared with the control leg) in bout 1 (122.9% +/- 2.6%; P
      < 0.001) and bout 2 (109.1% +/- 3.0%; P < 0.05). Compared with bout 1, the
      increase in NF-kappaB DNA-binding activity postexercise was attenuated after bout
      2 (P = 0.0008). Repeated eccentric exercise results in a contralateral repeated
      bout effect, which could be due to the attenuated increase in NF-kappaB activity
      postexercise. 

PMID- 23950164
TI  - L-Arginine supplementation improves antioxidant defenses through L
      arginine/nitric oxide pathways in exercised rats.
AB  - l-Arginine (l-Arg) supplementation has been shown to enhance physical exercise
      capacity and delay onset of fatigue. This work investigated the potential
      beneficial mechanism(s) of l-Arg supplementation by examining its effect on the
      cellular oxidative and nitrosative stress pathways in the exercised rats. Forty
      eight rats were randomly divided into six groups: sedentary control; sedentary
      control with l-Arg treatment; endurance training (daily swimming training for 8
      wk) control; endurance training with l-Arg treatment; an exhaustive exercise (one
      time swimming to fatigue) control; and an exhaustive exercise with l-Arg
      treatment. l-Arg (500 mg/kg body wt) or saline was given to rats by intragastric
      administration 1 h before the endurance training and the exhaustive swimming
      test. Expression levels and activities of the l-Arg/nitric oxide (NO) pathway
      components and parameters of the oxidative stress and antioxidant defense
      capacity were investigated in l-Arg-treated and control rats. The result show
      that the l-Arg supplementation completely reversed the exercise-induced
      activation of NO synthase and superoxide dismutase, increased l-Arg transport
      capacity, and increased NO and anti-superoxide anion levels. These data
      demonstrate that l-Arg supplementation effectively reduces the exercise-induced
      imbalance between oxidative stress and antioxidant defense capacity, and this
      modulation is likely mediated through the l-Arg/NO pathways. The findings of this
      study improved our understanding of how l-Arg supplementation prevents elevations
      of reactive oxygen species and favorably enhances the antioxidant defense
      capacity during physical exercise. 

PMID- 23950165
TI  - Development and validation of anthropometric prediction equations for estimation
      of lean body mass and appendicular lean soft tissue in Indian men and women.
AB  - Lean body mass (LBM) and muscle mass remain difficult to quantify in large
      epidemiological studies due to the unavailability of inexpensive methods. We
      therefore developed anthropometric prediction equations to estimate the LBM and
      appendicular lean soft tissue (ALST) using dual-energy X-ray absorptiometry (DXA)
      as a reference method. Healthy volunteers (n = 2,220; 36% women; age 18-79 yr),
      representing a wide range of body mass index (14-44 kg/m(2)), participated in
      this study. Their LBM, including ALST, was assessed by DXA along with
      anthropometric measurements. The sample was divided into prediction (60%) and
      validation (40%) sets. In the prediction set, a number of prediction models were
      constructed using DXA-measured LBM and ALST estimates as dependent variables and
      a combination of anthropometric indices as independent variables. These equations
      were cross-validated in the validation set. Simple equations using age, height,
      and weight explained >90% variation in the LBM and ALST in both men and women.
      Additional variables (hip and limb circumferences and sum of skinfold
      thicknesses) increased the explained variation by 5-8% in the fully adjusted
      models predicting LBM and ALST. More complex equations using all of the above
      anthropometric variables could predict the DXA-measured LBM and ALST accurately,
      as indicated by low standard error of the estimate (LBM: 1.47 kg and 1.63 kg for
      men and women, respectively), as well as good agreement by Bland-Altman analyses
      (Bland JM, Altman D. Lancet 1: 307-310, 1986). These equations could be a
      valuable tool in large epidemiological studies assessing these body compartments
      in Indians and other population groups with similar body composition. 

PMID- 23950166
TI  - Cardiovascular and autonomic responses to physiological stressors before and
      after six hours of water immersion.
AB  - The physiological responses to water immersion (WI) are known; however, the
      responses to stress following WI are poorly characterized. Ten healthy men were
      exposed to three physiological stressors before and after a 6-h resting WI (32-33
      degrees C): 1) a 2-min cold pressor test, 2) a static handgrip test to fatigue at
      40% of maximum strength followed by postexercise muscle ischemia in the
      exercising forearm, and 3) a 15-min 70 degrees  head-up-tilt (HUT) test. Heart
      rate (HR), systolic and diastolic blood pressure (SBP and DBP), cardiac output
      (Q), limb blood flow (BF), stroke volume (SV), systemic and calf or forearm
      vascular resistance (SVR and CVR or FVR), baroreflex sensitivity (BRS), and HR
      variability (HRV) frequency-domain variables [low-frequency (LF), high-frequency
      (HF), and normalized (n)] were measured. Cold pressor test showed lower HR, SBP,
      SV, Q, calf BF, LFnHRV, and LF/HFHRV and higher CVR and HFnHRV after than before
      WI (P < 0.05). Handgrip test showed no effect of WI on maximum strength and
      endurance and lower HR, SBP, SV, Q, and calf BF and higher SVR and CVR after than
      before WI (P < 0.05). During postexercise muscle ischemia, HFnHRV increased from
      baseline after WI only, and LFnHRV was lower after than before WI (P < 0.05). HUT
      test showed lower SBP, DBP, SV, forearm BF, and BRS and higher HR, FVR, LF/HFHRV,
      and LFnHRV after than before WI (P < 0.05). The changes suggest differential
      activation/depression during cold pressor and handgrip (reduced
      sympathetic/elevated parasympathetic) and HUT (elevated sympathetic/reduced
      parasympathetic) following 6 h of WI. 

PMID- 23950167
TI  - Time and volume dependence of dead space in healthy and surfactant-depleted rat
      lungs during spontaneous breathing and mechanical ventilation.
AB  - Volumetric capnography is a standard method to determine pulmonary dead space.
      Hereby, measured carbon dioxide (CO2) in exhaled gas volume is analyzed using the
      single-breath diagram for CO2. Unfortunately, most existing CO2 sensors do not
      work with the low tidal volumes found in small animals. Therefore, in this study,
      we developed a new mainstream capnograph designed for the utilization in small
      animals like rats. The sensor was used for determination of dead space volume in
      healthy and surfactant-depleted rats (n = 62) during spontaneous breathing (SB)
      and mechanical ventilation (MV) at three different tidal volumes: 5, 8, and 11
      ml/kg. Absolute dead space and wasted ventilation (dead space volume in relation
      to tidal volume) were determined over a period of 1 h. Dead space increase and
      reversibility of the increase was investigated during MV with different tidal
      volumes and during SB. During SB, the dead space volume was 0.21 +/- 0.14 ml and
      increased significantly at MV to 0.39 +/- 0.03 ml at a tidal volume of 5 ml/kg
      and to 0.6 +/- 0.08 ml at a tidal volume of 8 and 11 ml/kg. Dead space and wasted
      ventilation during MV increased with tidal volume. This increase was mostly
      reversible by switching back to SB. Surfactant depletion had no further influence
      on the dead space increase during MV, but impaired the reversibility of the dead
      space increase. 

PMID- 23950168
TI  - Changes in circulating microRNAs levels with exercise modality.
AB  - Here, we studied muscle-specific and muscle-related miRNAs in plasma of
      exercising humans. Our aim was to determine whether they are affected by
      eccentric and/or concentric exercise modes and could be biomarkers of muscle
      injuries or possible signaling molecules. On two separate days, nine healthy
      subjects randomly performed two 30-min walking exercises, one downhill (high
      eccentric component) and one uphill (high concentric component). Perceived
      exertion and heart rate were higher during the uphill exercise, while subjective
      pain and ankle plantar flexor strength losses within the first 48-h were higher
      following the downhill exercise. Both exercises increased serum creatine kinase
      and myoglobin with no significant differences between conditions. Plasma levels
      of circulating miRNAs assessed before, immediately after, and at 2-, 6-, 24-, 48
      , and 72-h recovery showed that 1) hsa-mir-1, 133a, 133b, and 208b were not
      affected by concentric exercise but significantly increased during early recovery
      of eccentric exercise (2 to 6 h); 2) hsa-mir-181b and 214 significantly and
      transiently increased immediately after the uphill, but not downhill, exercise.
      The muscle-specific hsa-mir-206 was not reliably quantified and cardiac-specific
      hsa-mir-208a remained undetectable. In conclusion, changes in circulating miRNAs
      were dependent on the exercise mode. Circulating muscle-specific miRNAs primarily
      responded to a downhill exercise (high eccentric component) and could potentially
      be alternative biomarkers of muscle damage. Two muscle-related miRNAs primarily
      responded to an uphill exercise (high exercise intensity), suggesting they could
      be markers or mediators of physiological adaptations. 

PMID- 23950169
TI  - Cancer makes new friends with old tricks.
AB  - In this issue of Blood, Zhang and colleagues report the identification of a novel
      subset of circulating myeloid cells with immunosuppressive activity in pediatric
      patients with metastatic sarcomas.

PMID- 23950170
TI  - Importance of subsegmental pulmonary embolism.
AB  - In this issue of Blood, den Exter et al highlight the importance of subsegmental
      pulmonary emboli.

PMID- 23950171
TI  - Ruxolitinib targets DCs: for better or worse?
AB  - In this issue of Blood, Heine et al demonstrate the dose-dependent inhibitory
      effect of ruxolitinib on the generation of dendritic cells (DCs) from monocytes.
      The drug also inhibited DC activation, tissue migration, and induction of
      allogeneic or antigen-specific T-cell responses, including in vivo viral
      clearance.

PMID- 23950172
TI  - The sequence of events in diffuse large B-cell lymphoma.
AB  - In this issue of Blood, Morin et al report their findings on complete genome
      sequence analysis of primary diffuse large B-cell lymphoma (DLBCL) primary tumors
      and cell lines and reveal novel somatic point mutations, rearrangements, and
      fusions. Importantly, they also demonstrate the temporal acquisition of
      mutations, providing insight into the evolution of mutations occurring in DLBCL.

PMID- 23950173
TI  - PNH from mutations of another PIG gene.
AB  - In this issue of Blood, Krawitz et al report on a patient with paroxysmal
      nocturnal hemoglobinuria (PNH) who does not have a mutation of PIG-A, but in whom
      instead both alleles of PIG-T (another gene involved in
      glucosylphosphatidylinositol [GPI] biosynthesis) have inactivating mutations, one
      in the germ line and one somatic.

PMID- 23950174
TI  - CMV: a warrior against leukemia?
AB  - In this issue of Blood, Green et al provide additional information supporting
      that cytomegalovirus (CMV) reduces leukemia relapse after allogeneic stem cell
      transplantation.

PMID- 23950176
TI  - Human secondary lymphoid organs typically contain polyclonally-activated
      proliferating regulatory T cells.
AB  - Immunomodulating regulatory T-cell (Treg) therapy is a promising strategy in
      autoimmunity and transplantation. However, to achieve full clinical efficacy,
      better understanding of in vivo human Treg biology is warranted. Here, we
      demonstrate that in contrast to blood and bone marrow Tregs, which showed a
      resting phenotype, the majority of CD4(pos)CD25(pos)CD127(neg)FoxP3(pos) Tregs in
      secondary lymphoid organs were proliferating activated CD69(pos)CD45RA(neg) cells
      with a hyperdemethylated FOXP3 gene and a broad T-cell receptor-Vbeta repertoire,
      implying polyclonal activation. Activated CD69(pos) Tregs were distributed over
      both T-cell and B-cell areas, distant from Aire(pos) and CD11c(pos) cells. In
      contrast to the anergic peripheral blood Tregs, lymphoid organ Tregs had
      significant ex vivo proliferative capacity and produced cytokines like
      interleukin-2, while revealing similar suppressive potential. Also, next to Treg
      expressing chemokine receptors important for a prolonged stay in lymphoid organs,
      a significant part of the cells expressed peripheral tissue-associated,
      functional homing markers. In conclusion, our data suggest that human secondary
      lymphoid organs aid in the maintenance and regulation of Treg function and
      homeostasis. This knowledge may be exploited for further optimization of Treg
      immunotherapy, for example, by ex vivo selection of Tregs with capacity to
      migrate to lymphoid organs providing an in vivo platform for further Treg
      expansion. 

PMID- 23950177
TI  - Ubiquitin-mediated interaction of p210 BCR/ABL with beta-catenin supports disease
      progression in a murine model for chronic myelogenous leukemia.
AB  - We have identified a ubiquitin-binding domain within the NH2-terminal sequences
      of p210 BCR/ABL and determined that the binding site co-localizes with the
      binding site for beta-catenin. The domain does not support the auto- or trans
      kinase activity of p210 BCR/ABL or its ability to interact with GRB2 and activate
      ERK1/2 signaling. Expression of p210 BCR/ABL, but not a beta-catenin-binding
      mutant, in hematopoietic cells is associated with the accumulation of p-beta
      catenin (Tyr654) and increased TCF/LEF-mediated transcription. In a bone marrow
      transplantation model, the interaction between beta-catenin and p-beta-catenin
      (Tyr654) is detectable in mice transplanted with p210 BCR/ABL, but not the
      mutant. Whereas mice transplanted with p210 BCR/ABL exhibit myeloid disease with
      expansion of monocytes and neutrophils, mice transplanted with the mutant
      predominantly exhibit expansion of neutrophils, polycythemia, and increased
      lifespan. The increased disease latency is associated with expansion of
      megakaryocyte-erythrocyte progenitors, a decrease in common myeloid progenitors,
      and reduced beta-catenin signaling in the bone marrow of the diseased mice. These
      observations support a model in which p210 BCR/ABL may influence lineage-specific
      leukemic expansion by directly binding and phosphorylating beta-catenin and
      altering its transcriptional activity. They further suggest that the interaction
      may play a role in chronic phase disease progression.

PMID- 23950178
TI  - PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in
      patients with relapsed and bortezomib-refractory myeloma.
AB  - Panobinostat is an oral pan-deacetylase inhibitor that synergizes with bortezomib
      to inhibit both the aggresome and proteasome pathways in preclinical studies.
      PANORAMA 2 is a phase 2 trial of panobinostat in combination with bortezomib and
      dexamethasone to treat patients with relapsed and bortezomib-refractory multiple
      myeloma (with >=2 prior lines of therapy, including an immunomodulatory drug, and
      patients who had progressed on or within 60 days of the last bortezomib-based
      therapy). Fifty-five heavily pretreated patients were enrolled (median, 4 prior
      regimens, including a median of 2 prior bortezomib-containing regimens). The
      overall response rate was 34.5% (1 near-complete response and 18 partial
      responses). An additional 10 patients achieved minimal response, for a clinical
      benefit rate of 52.7%. Median exposure and progression-free survival were 4.6 and
      5.4 months, respectively. In patients who achieved a response, median time to
      response was 1.4 months, and median duration of response was 6.0 months. Common
      grade 3/4 adverse events, regardless of study drug relationship, included
      thrombocytopenia (63.6%), fatigue (20.0%), and diarrhea (20.0%). Only 1 patient
      had grade 3 peripheral neuropathy. Panobinostat, when combined with bortezomib
      and dexamethasone, can recapture responses in heavily pretreated, bortezomib
      refractory multiple myeloma patients. This trial was registered at
      www.clinicaltrials.gov as #NCT01083602. 

PMID- 23950179
TI  - Human milk hyaluronan enhances innate defense of the intestinal epithelium.
AB  - Breast-feeding is associated with enhanced protection from gastrointestinal
      disease in infants, mediated in part by an array of bioactive glycan components
      in milk that act through molecular mechanisms to inhibit enteric pathogen
      infection. Human milk contains hyaluronan (HA), a glycosaminoglycan polymer found
      in virtually all mammalian tissues. We have shown that synthetic HA of a specific
      size range promotes expression of antimicrobial peptides in intestinal
      epithelium. We hypothesize that hyaluronan from human milk also enhances innate
      antimicrobial defense. Here we define the concentration of HA in human milk
      during the first 6 months postpartum. Importantly, HA isolated from milk has a
      biological function. Treatment of HT-29 colonic epithelial cells with human milk
      HA at physiologic concentrations results in time- and dose-dependent induction of
      the antimicrobial peptide human beta-defensin 2 and is abrogated by digestion of
      milk HA with a specific hyaluronidase. Milk HA induction of human beta-defensin 2
      expression is also reduced in the presence of a CD44-blocking antibody and is
      associated with a specific increase in ERK1/2 phosphorylation, suggesting a role
      for the HA receptor CD44. Furthermore, oral administration of human milk-derived
      HA to adult, wild-type mice results in induction of the murine Hbeta D2 ortholog
      in intestinal mucosa and is dependent upon both TLR4 and CD44 in vivo. Finally,
      treatment of cultured colonic epithelial cells with human milk HA enhances
      resistance to infection by the enteric pathogen Salmonella typhimurium. Together,
      our observations suggest that maternally provided HA stimulates protective
      antimicrobial defense in the newborn. 

PMID- 23950180
TI  - Noncanonical transforming growth factor beta (TGFbeta) signaling in cranial
      neural crest cells causes tongue muscle developmental defects.
AB  - Microglossia is a congenital birth defect in humans and adversely impacts quality
      of life. In vertebrates, tongue muscle derives from the cranial mesoderm, whereas
      tendons and connective tissues in the craniofacial region originate from cranial
      neural crest (CNC) cells. Loss of transforming growth factor beta (TGFbeta) type
      II receptor in CNC cells in mice (Tgfbr2(fl/fl);Wnt1-Cre) causes microglossia due
      to a failure of cell-cell communication between cranial mesoderm and CNC cells
      during tongue development. However, it is still unclear how TGFbeta signaling in
      CNC cells regulates the fate of mesoderm-derived myoblasts during tongue
      development. Here we show that activation of the cytoplasmic and nuclear tyrosine
      kinase 1 (ABL1) cascade in Tgfbr2(fl/fl);Wnt1-Cre mice results in a failure of
      CNC-derived cell differentiation followed by a disruption of TGFbeta-mediated
      induction of growth factors and reduction of myogenic cell proliferation and
      differentiation activities. Among the affected growth factors, the addition of
      fibroblast growth factor 4 (FGF4) and neutralizing antibody for follistatin (FST;
      an antagonist of bone morphogenetic protein (BMP)) could most efficiently restore
      cell proliferation, differentiation, and organization of muscle cells in the
      tongue of Tgfbr2(fl/fl);Wnt1-Cre mice. Thus, our data indicate that CNC-derived
      fibroblasts regulate the fate of mesoderm-derived myoblasts through TGFbeta
      mediated regulation of FGF and BMP signaling during tongue development. 

PMID- 23950181
TI  - A bacterial glucanotransferase can replace the complex maltose metabolism
      required for starch to sucrose conversion in leaves at night.
AB  - Controlled conversion of leaf starch to sucrose at night is essential for the
      normal growth of Arabidopsis. The conversion involves the cytosolic metabolism of
      maltose to hexose phosphates via an unusual, multidomain protein with 4
      glucanotransferase activity, DPE2, believed to transfer glucosyl moieties to a
      complex heteroglycan prior to their conversion to hexose phosphate via a
      cytosolic phosphorylase. The significance of this complex pathway is unclear;
      conversion of maltose to hexose phosphate in bacteria proceeds via a more typical
      4-glucanotransferase that does not require a heteroglycan acceptor. It has
      recently been suggested that DPE2 generates a heterogeneous series of terminal
      glucan chains on the heteroglycan that acts as a "glucosyl buffer" to ensure a
      constant rate of sucrose synthesis in the leaf at night. Alternatively, DPE2
      and/or the heteroglycan may have specific properties important for their function
      in the plant. To distinguish between these ideas, we compared the properties of
      DPE2 with those of the Escherichia coli glucanotransferase MalQ. We found that
      MalQ cannot use the plant heteroglycan as an acceptor for glucosyl transfer.
      However, experimental and modeling approaches suggested that it can potentially
      generate a glucosyl buffer between maltose and hexose phosphate because, unlike
      DPE2, it can generate polydisperse malto-oligosaccharides from maltose.
      Consistent with this suggestion, MalQ is capable of restoring an essentially wild
      type phenotype when expressed in mutant Arabidopsis plants lacking DPE2. In light
      of these findings, we discuss the possible evolutionary origins of the complex
      DPE2-heteroglycan pathway. 

PMID- 23950182
TI  - Systems-level modeling with molecular resolution elucidates the rate-limiting
      mechanisms of cellulose decomposition by cellobiohydrolases.
AB  - Interprotein and enzyme-substrate couplings in interfacial biocatalysis induce
      spatial correlations beyond the capabilities of classical mass-action principles
      in modeling reaction kinetics. To understand the impact of spatial constraints on
      enzyme kinetics, we developed a computational scheme to simulate the reaction
      network of enzymes with the structures of individual proteins and substrate
      molecules explicitly resolved in the three-dimensional space. This methodology
      was applied to elucidate the rate-limiting mechanisms of crystalline cellulose
      decomposition by cellobiohydrolases. We illustrate that the primary bottlenecks
      are slow complexation of glucan chains into the enzyme active site and excessive
      enzyme jamming along the crowded substrate. Jamming could be alleviated by
      increasing the decomplexation rate constant but at the expense of reduced
      processivity. We demonstrate that enhancing the apparent reaction rate required a
      subtle balance between accelerating the complexation driving force and
      simultaneously avoiding enzyme jamming. Via a spatiotemporal systems analysis, we
      developed a unified mechanistic framework that delineates the experimental
      conditions under which different sets of rate-limiting behaviors emerge. We found
      that optimization of the complexation-exchange kinetics is critical for
      overcoming the barriers imposed by interfacial confinement and accelerating the
      apparent rate of enzymatic cellulose decomposition. 

PMID- 23950183
TI  - Combination of echocardiographic and pulmonary function test measures improves
      sensitivity for diagnosis of systemic sclerosis-associated pulmonary arterial
      hypertension: analysis of 2 cohorts.
AB  - OBJECTIVE: To evaluate routinely collected non-invasive tests from 2 systemic
      sclerosis (SSc) cohorts to determine their predictive value alone and in
      combination versus right heart catheterization (RHC)-confirmed pulmonary arterial
      hypertension (PAH). METHODS: We evaluated 2 cohorts of patients who were at risk
      or with incident PAH: (1) The Pulmonary Hypertension Assessment and Recognition
      Outcomes in Scleroderma (PHAROS) cohort and (2) an inception SSc cohort at Cochin
      Hospital, Paris, France. Estimated right ventricular systolic pressure (eRVSP) as
      determined by transthoracic echocardiogram (TTE) and pulmonary function test
      (PFT) measures was evaluated, and the predictive values determined. We then
      evaluated patients with PAH missed on TTE cutoffs that were subsequently
      identified by a PFT measure. RESULTS: In the PHAROS cohort (n = 206), 59 (29%)
      had RHC-defined PAH. An eRVSP threshold of 35-50 mm Hg failed to diagnose PAH in
      7% to 31% of patients, 50% to 70% of which (n = 2-13) were captured by PFT
      measures. In the Cochin cohort (n = 141), 10 (7%) patients had RHC confirmed PAH.
      An eRVSP threshold of 35-50 mm Hg missed 0% to 70% (n = 0-7) of patients, of
      which 0% to 68% (n = 0-6) were met by PFT measures. The combination of TTE and
      PFT improved the negative predictive value for diagnosing PAH. CONCLUSION: In 2
      large SSc cohorts, screening with TTE and PFT captured a majority of patients
      with PAH. TTE and PFT complement each other for the diagnosis of PAH.

PMID- 23950184
TI  - High doses of infliximab in the management of juvenile idiopathic arthritis.
AB  - OBJECTIVE: To review our experiences with high-dose infliximab (IFX) to treat
      juvenile idiopathic arthritis (JIA). We routinely use high doses of IFX (10-20
      mg/kg) in children with recalcitrant or highly active JIA. Although biologics
      have revolutionized treatment of JIA, many patients have active disease despite
      therapy. Studies have shown benefits of high-dose IFX in several conditions,
      including inflammatory bowel disease, psoriasis, and idiopathic uveitis. The
      safety and effectiveness of high-dose IFX have not been evaluated in JIA.
      METHODS: We performed a retrospective review of children with JIA who received
      IFX >= 10 mg/kg. We recorded all serious adverse events (SAE), medically
      important infections, and infusion reactions. We also recorded the physician
      global assessment of disease activity (MD global) and active joint count (AJC) at
      initiation of high-dose IFX and 3, 6, and 12 months thereafter. RESULTS: Fifty
      eight subjects received a total of 1064 infusions over 95 person-years. There
      were a total of 9 SAE (9.5/100 person-yrs), 7 of which were potentially related
      to therapy, and 6 infusion reactions (0.5%), none constituting anaphylaxis.
      Statistically significant improvements were observed in the AJC (median 0, range
      0-31, vs 2, 0-39) and MD global (12, 2-31, vs 22, 5-80) over the first year.
      CONCLUSION: High-dose IFX appears safe in the management of JIA. Future
      prospective controlled studies are necessary to evaluate its safety and efficacy.

PMID- 23950185
TI  - Five-year favorable outcome of patients with early rheumatoid arthritis in the
      2000s: data from the ESPOIR cohort.
AB  - OBJECTIVE: To report the 5-year outcome of a large prospective cohort of patients
      with very early rheumatoid arthritis (RA), and to identify factors predictive of
      outcome. METHODS: Patients were recruited if they had early arthritis of < 6
      months' duration, had a high probability of developing RA, and had never been
      prescribed disease-modifying antirheumatic drugs (DMARD) or steroids. Logistic
      regression analysis was used to determine factors that predict outcome. RESULTS:
      We included 813 patients from December 2002 to April 2005. Age was 48.1 +/- 12.6
      years, delay before referral 103.1 +/- 52.4 days, 28-joint Disease Activity Score
      (DAS28) 5.1 +/- 1.3, Health Assessment Questionnaire (HAQ) 1.0 +/- 0.7; 45.8% and
      38.7% had rheumatoid factor or antibodies to cyclic citrullinated peptide (anti
      CCP), respectively; 22% had hand or foot erosions; 78.5% fulfilled the American
      College of Rheumatology/European League Against Rheumatism criteria for RA at
      baseline and 93.8% during followup. At 5 years, 573 patients were evaluated. The
      outcome was mild for most patients: disease activity (median DAS28 = 2.5) and HAQ
      disability (median 0.3) were well controlled over time; 50.6% achieved DAS28
      remission and 64.7% low disease activity. Radiographic progression was low (2.9
      Sharp unit/year) and only a few patients required joint surgery. Nevertheless,
      some patients developed new comorbidities. During the 5 years, 82.7% of patients
      had received at least 1 DMARD (methotrexate, 65.9%), 18.3% a biological DMARD,
      and about 60% prednisone at least once. Anti-CCP was the best predictor of
      remaining in the cohort for 5 years, of prescription of synthetic or biologic
      DMARD, and of radiographic progression. CONCLUSION: The 5-year outcome of an
      early RA cohort in the 2000s was described. Anti-CCP was a robust predictor of
      outcome. The generally good 5-year outcome could be related to early referral and
      early effective treatment, key processes in the management of early RA in daily
      practice.

PMID- 23950186
TI  - A randomized controlled trial of an internal family systems-based
      psychotherapeutic intervention on outcomes in rheumatoid arthritis: a proof-of
      concept study.
AB  - OBJECTIVE: To conduct a proof-of-concept randomized trial of an Internal Family
      Systems (IFS) psychotherapeutic intervention on rheumatoid arthritis (RA) disease
      activity and psychological status. METHODS: Patients with RA were randomized to
      either an IFS group for 9 months (n = 39) or an education (control) group (n =
      40) that received mailed materials on RA symptoms and management. The groups were
      evaluated every 3 months until intervention end and 1 year later. Self-assessed
      joint pain (RA Disease Activity Index joint score), Short Form-12 physical
      function score, visual analog scale for overall pain and mental health status
      (Beck Depression Inventory, and State Trait Anxiety Inventory) were assessed. The
      28-joint Disease Activity Score-C-reactive Protein 4 was determined by
      rheumatologists blinded to group assignment. Treatment effects were estimated by
      between-group differences, and mixed model repeated measures compared trends
      between study arms at 9 months and 1 year after intervention end. RESULTS: Of 79
      participants randomized, 68 completed the study assessments and 82% of the IFS
      group completed the protocol. Posttreatment improvements favoring the IFS group
      occurred in overall pain [mean treatment effects -14.9 (29.1 SD); p = 0.04], and
      physical function [14.6 (25.3); p = 0.04]. Posttreatment improvements were
      sustained 1 year later in self-assessed joint pain [-0.6 (1.1); p = 0.04], self
      compassion [1.8 (2.8); p = 0.01], and depressive symptoms [-3.2 (5.0); p =0.01].
      There were no sustained improvements in anxiety, self-efficacy, or disease
      activity. CONCLUSION: An IFS-based intervention is feasible and acceptable to
      patients with RA and may complement medical management of the disease. Future
      efficacy trials are warranted. ClinicalTrials.gov identifier: NCT00869349.

PMID- 23950188
TI  - Disease factors in early rheumatoid arthritis are associated with differential
      risks for cardiovascular events and mortality depending on age at onset: a 10
      year observational cohort study.
AB  - OBJECTIVE: To investigate, within the first 2 years of diagnosis with rheumatoid
      arthritis (RA), associations between disease-related measures and cardiovascular
      disease (CVD) and mortality in patients with RA onset before and after 65 years
      of age. METHODS: The study population (n = 741; 67.5% women) was derived from the
      Better Anti-Rheumatic Pharmaco Therapy (BARFOT) early RA cohort, recruited 1993
      1999. The mean age was 55 years (SD 14.7). The outcomes were incident CVD events
      and all-cause mortality until 2010. Area under the curve (AUC) for disease
      measures at inclusion, 1 and 2 years, and decrease in measures after 1 year were
      calculated. RESULTS: In all, 177 CVD events and 151 deaths occurred over 10 years
      of observation. In adjusted Cox regression analyses, seropositivity for
      rheumatoid factor (RF) or anticitrullinated protein antibodies (ACPA); white
      blood (cell) count at diagnosis; and AUC of C-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR), and visual analog scale (VAS)-pain were associated with
      higher CVD risk among patients with disease onset before 65 years of age. Among
      patients with disease onset after 65 years, larger decreases in CRP, ESR, health
      assessment questionnaire (HAQ), and use of methotrexate decreased CVD risk,
      whereas use of glucocorticoids heightened CVD risk. AUC of CRP, ESR, HAQ, and HAQ
      after 2 years was related to risk of death in both age groups. Seropositivity and
      AUC for VAS-pain in the younger group and use of glucocorticoids in the elderly
      were associated with poorer survival. CONCLUSION: Early treatment of RA may
      improve longterm outcomes. Presence of RF or ACPA associates with CVD and
      mortality among RA patients with disease onset before 65 years. Age
      stratification may improve evaluation of risk for CVD and mortality in early RA.

PMID- 23950187
TI  - Comparison of the disease activity score using erythrocyte sedimentation rate and
      C-reactive protein in African Americans with rheumatoid arthritis.
AB  - OBJECTIVE: The Disease Activity Score based on 28 joints (DAS28) has been
      increasingly used in clinical practice and research studies of rheumatoid
      arthritis (RA). Studies have reported discordance between DAS28 based on
      erythrocyte sedimentation rate (ESR) versus C-reactive protein (CRP) in patients
      with RA. However, such comparison is lacking in African Americans with RA.
      METHODS: This analysis included participants from the Consortium for the
      Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis
      (CLEAR) registry, which enrolls self-declared African Americans with RA. Using
      tender and swollen joint counts, separate ESR-based and CRP-based DAS28 scores
      (DAS28-ESR3 and DAS28-CRP3) were calculated, as were DAS28-ESR4 and DAS28-CRP4,
      which included the patient's assessment of disease activity. The scores were
      compared using paired t-test, simple agreement and kappa, correlation
      coefficient, and Bland-Altman plots. RESULTS: Of the 233 included participants,
      85% were women, mean age at enrollment was 52.6 years, and median disease
      duration at enrollment was 21 months. Mean DAS28-ESR3 was significantly higher
      than DAS28-CRP3 (4.8 vs 3.9; p < 0.001). Similarly, mean DAS28-ESR4 was
      significantly higher than DAS28-CRP4 (4.7 vs 3.9; p < 0.001). ESR-based DAS28
      remained higher than CRP-based DAS28 even when stratified by age, sex, and
      disease duration. Overall agreement was not high between DAS28-ESR3 and DAS28
      CRP3 (50%) or between DAS28-ESR4 and DAS28-CRP4 (59%). DAS28-CRP3 underestimated
      disease activity in 47% of the participants relative to DAS28-ESR3 and DAS28-CRP4
      in 40% of the participants relative to DAS28-ESR4. CONCLUSION: There was
      significant discordance between the ESR-based and CRP-based DAS28, a situation
      that could affect clinical treatment decisions for African Americans with RA.

PMID- 23950189
TI  - Are young women and men with rheumatoid arthritis at risk for fragility
      fractures? A population-based study.
AB  - OBJECTIVE: Older women and men with rheumatoid arthritis (RA) are at increased
      risk for fractures, but limited information is available on fracture risk in
      younger individuals with RA and whether such risk occurs early in the disease
      onset or only when older. We determined the risk for fractures in both young and
      older women and men following RA diagnosis. METHODS: We studied a population
      based inception cohort with RA from Olmsted County, Minnesota, USA. We identified
      822 women and 349 men diagnosed with RA between 1955 and 2007 (308 women and 110
      men diagnosed before age 50) and an equal number of paired non-RA subjects,
      matched by sex and birth year. Incident fractures were collected through review
      of complete (inpatient and outpatient) medical records available through the
      linkage system of the Rochester Epidemiology Project. RESULTS: The hazard ratio
      (HR; 95% CI) for a non-pathologic fracture occurring from no more than moderate
      trauma was 1.63 (1.36-1.96) for women and 1.40 (1.02-1.93) for men with RA.
      Findings were consistent for women and men diagnosed with RA at age >= 50 years
      [HR, 1.43 (1.16-1.77) and 1.34 (0.92-1.94), respectively], or at age < 50 years
      [HR, 2.34 (1.61-3.42) and 1.74 (0.91-3.30), respectively]. However, young women,
      but not young men, with RA were at increased fracture risk even before age 50
      years (HR, 1.95 [1.08-3.51] and 0.82 [0.28-2.45], respectively). CONCLUSION:
      Young men with RA are at increased risk for fractures only when older, whereas
      young women with RA have an elevated fracture risk even while still young.

PMID- 23950190
TI  - Stressful life events antedating chronic childhood arthritis.
AB  - OBJECTIVE: To investigate associations between antecedent stressful life events
      and occurrence of juvenile arthritis (JA). METHODS: The study population
      comprised patients with JA referred to a pediatric rheumatology clinic between
      1981 and 2010. A questionnaire, which was developed as a screening tool by the
      clinic, was completed at the first clinic visit by patients' parents and, for
      comparison, by parents of unrelated age, sex, geographically, and temporally
      matched healthy controls. The entire questionnaire captured a broad array of
      clinical, demographic, psychosocial, and environmental data, including questions
      about stressful life events from 686 patients with JA and from 1042 controls.
      RESULTS: Patients were more likely to have experienced a serious upset (OR 4.81;
      p < 0.0001), a currently ill family member (OR 2.29; p < 0.0001), separated
      parents (OR 1.96; p < 0.0001), or difficulties with interpersonal relationships
      (OR 2.54; p < 0.0001) prior to first clinic presentation compared to controls.
      Children with oligoarticular JA were more likely than controls to have
      experienced a serious upset (OR 3.46; p = 0.008), an ill family member (OR 3.79;
      CI 2.02, 7.11; p < 0.0001), or problems with interpersonal interactions (OR 3.32;
      p < 0.0001). Children with polyarticular JA were more likely to have experienced
      a serious upset (OR 5.68; p < 0.0001), separated parents (OR 2.66; p = 0.001), a
      deceased parent (OR 6.75, p = 0.017), or problems with interpersonal
      relationships (OR 2.39; p = 0.009). No significant differences were observed when
      comparing systemic JA patients to controls. CONCLUSION: Strong associations
      between stressful life events antedating the first clinic visit of patients with
      JA indicate that life event stresses should be identified and addressed when
      first encountering and managing children with JA.

PMID- 23950191
TI  - Increase in bone density in patients with spondyloarthritis during anti-tumor
      necrosis factor therapy: 6-year followup study.
AB  - OBJECTIVE: To assess the effects on bone mineral density (BMD) of prolonged anti
      tumor necrosis factor (anti-TNF) therapy in patients with spondyloarthritis
      (SpA); to compare the BMD changes to those observed in SpA patients not treated
      with anti-TNF; and to identify the predictors of these changes. METHODS: Fifty
      nine patients with SpA according to the European Spondylarthropathy Study Group
      criteria who were treated with anti-TNF therapy for at least 4 years were
      included. Thirty-four patients with SpA from an international longitudinal
      observational study (OASIS cohort) were used as a control group. Lumbar spine and
      hip BMD were measured by dual-energy x-ray absorptiometry at baseline, after 1
      year, and after at least 4 years. RESULTS: Over an average 6.5 years' followup,
      the increase in BMD was 11.8% (+/- 12.8%) at the lumbar spine (p < 0.0001) and
      3.6% (+/- 9.3%) at the great trochanter (p = 0.0001) in patients treated with
      anti-TNF. At the lumbar spine, the increase was similar in patients with and
      those without syndesmophytes. BMD changes were significantly higher in the anti
      TNF group than in the control group at lumbar spine (p < 0.0001), at femoral neck
      (p = 0.002), and at trochanter (p = 0.011), but not at total hip (p = 0.062).
      Multivariate analysis showed that the predictors of lumbar spine BMD changes in
      the total population were the use of anti-TNF (p < 0.0001) and, in the anti-TNF
      therapy group, the 1-year lumbar spine BMD change (p = 0.007). CONCLUSION: This
      study shows that prolonged anti-TNF therapy increases lumbar spine and trochanter
      BMD. This effect should be taken into account before introducing antiosteoporotic
      treatment in these patients.

PMID- 23950192
TI  - Sensory preconditioning in newborn rabbits: from common to distinct odor
      memories.
AB  - This study evaluated whether olfactory preconditioning is functional in newborn
      rabbits and based on joined or independent memory of odorants. First, after
      exposure to odorants A+B, the conditioning of A led to high responsiveness to
      odorant B. Second, responsiveness to B persisted after amnesia of A. Third,
      preconditioning was also functional with two overlapping pairs of odorants (A+B
      and B+C) and amnesia of one odorant did not affect memory of the others. Thus,
      incidental pairing of odorants allows reinforcement of one odorant to implicitly
      reinforce the others, the bond then vanishes, and the memory of each element
      becomes independent. 

PMID- 23950193
TI  - Voltage-dependent intrinsic bursting in olfactory bulb Golgi cells.
AB  - In the mammalian olfactory bulb (OB), local synaptic circuits modulate the
      evolving pattern of activity in mitral and tufted cells following olfactory
      sensory stimulation. GABAergic granule cells, the most numerous interneuron
      subtype in this brain region, have been extensively studied. However, classic
      studies using Golgi staining methods identified many other, nongranule cell types
      in the OB whose function remains mysterious. Within just the granule cell layer
      (GCL), Ramon y Cajal described multiple morphologically distinct subtypes of
      nongranule interneurons including large spiny Blanes cells which exhibit
      intrinsic persistent activity. Here, we define the intrinsic electrophysiology of
      a different nongranule interneuronal cell type in the GCL described by Ramon y
      Cajal, sparsely spiny Golgi cells in the rat OB. Golgi cells exhibit two distinct
      firing modes depending on the membrane potential: tonic firing and bursting.
      Golgi cells also generate rebound bursts following the offset of hyperpolarizing
      steps. We find that both low-threshold burst responses to depolarizing inputs and
      rebound bursts are blocked by nickel, an antagonist of T-type voltage-gated Ca2+
      current. The state-dependent firing behavior we report in OB Golgi cells suggests
      that the function of these interneurons may dynamically shift from providing
      rhythmic potent inhibition of postsynaptic target neurons at sniffing frequencies
      to tonic, subtractive inhibition based on centrifugal modulatory input.

PMID- 23950194
TI  - Memory retrieval before or after extinction reduces recovery of fear in
      adolescent rats.
AB  - Adolescent rats exhibit impaired extinction retention compared to pre-adolescent
      and adult rats. A single nonreinforced exposure to the conditioned stimulus (CS;
      a retrieval trial) given shortly before extinction has been shown in some
      circumstances to reduce the recovery of fear after extinction in adult animals.
      This study investigated whether a retrieval-extinction procedure would reduce the
      recovery of extinguished fear in adolescent rats. Furthermore, the effect of the
      retrieval-extinction sequence on fear recovery was examined by presenting the
      retrieval trial following extinction to some animals. In Experiment 1 adolescent
      rats received one nonreinforced CS presentation (a retrieval trial) or equivalent
      context exposure (no retrieval) 10 min before fear extinction. A retrieval trial
      shortly before extinction reduced overall levels of fear in both test contexts
      (i.e., it improved extinction retention and reduced renewal). In Experiment 2 a
      weakening of renewal was observed with a retrieval-extinction manipulation,
      regardless of whether the retrieval trial occurred in the training or extinction
      context. A key result was that a retrieval trial 10 min, but not 6 h, after
      extinction led to reduced overall levels of fear similar to that observed if the
      retrieval trial was given before extinction (Experiments 3 and 4), inconsistent
      with the current interpretation of the reduction in relapse being due to a
      disruption of reconsolidation. Together, these findings show that the impaired
      extinction retention observed in adolescents can be ameliorated by a very simple
      behavioral manipulation, but also raise some questions about the mechanisms
      underlying the retrieval-extinction effect. 

PMID- 23950196
TI  - A bee in the bonnet about honey and healing.

PMID- 23950197
TI  - A footballer's finger injury.

PMID- 23950195
TI  - Safety and efficacy of intravenous iron therapy in reducing requirement for
      allogeneic blood transfusion: systematic review and meta-analysis of randomised
      clinical trials.
AB  - OBJECTIVES: To evaluate the efficacy and safety of intravenous iron, focusing
      primarily on its effects on haemoglobin, requirement for transfusion, and risk of
      infection. DESIGN: Systematic review and meta-analysis of randomised controlled
      trials investigating the safety and efficacy of intravenous iron therapy. DATA
      SOURCES: Randomised controlled trials from Medline, Embase, and the Cochrane
      Central Register of Controlled Trials from 1966 to June 2013, with no language
      restrictions. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible trials were
      randomised controlled trials of intravenous iron compared with either no iron or
      oral iron. Crossover and observational studies were excluded. MAIN OUTCOME
      MEASURES: Change in haemoglobin concentration and risk of allogeneic red blood
      cell transfusion (efficacy) and risk of infection (safety). RESULTS: Of the 75
      trials meeting the inclusion criteria, 72 studies including 10 605 patients
      provided quantitative outcome data for meta-analysis. Intravenous iron was
      associated with an increase in haemoglobin concentration (standardised mean
      difference 6.5 g/L, 95% confidence interval 5.1 g/L to 7.9 g/L) and a reduced
      risk of requirement for red blood cell transfusion (risk ratio 0.74, 95%
      confidence interval 0.62 to 0.88), especially when intravenous iron was used with
      erythroid stimulating agents (ESAs) or in patients with a lower baseline plasma
      ferritin concentration. There were no significant interactions between the
      efficacy of intravenous iron and type or dose administered. Intravenous iron was,
      however, associated with a significant increase in risk of infection (relative
      risk 1.33, 95% confidence interval 1.10 to 1.64) compared with oral or no iron
      supplementation. The results remained similar when only high quality trials were
      analysed. CONCLUSIONS: Intravenous iron therapy is effective in increasing
      haemoglobin concentration and reducing the risk of allogeneic red blood cell
      transfusion and could have broad applicability to a range of acute care settings.
      This potential benefit is counterbalanced by a potential increased risk of
      infection.

PMID- 23950198
TI  - Opioids in the UK: what's the problem?

PMID- 23950199
TI  - MPs call for investigation into how psychiatric patients are being detained.

PMID- 23950200
TI  - New inspection regime in England sees Whipps Cross hospital downgraded.

PMID- 23950202
TI  - Doctors like emailing patients but want to be paid for it, study finds.

PMID- 23950204
TI  - Charity pulls out of Somalia after 22 years because of violence and abuse.

PMID- 23950203
TI  - Research into universal health coverage rises despite economic downturn, report
      finds.

PMID- 23950205
TI  - A qualitative study comparing experiences of the surgical safety checklist in
      hospitals in high-income and low-income countries.
AB  - OBJECTIVE: Bold claims have been made for the ability of the WHO surgical
      checklist to reduce surgical morbidity and mortality and improve patient safety
      regardless of the setting. Little is known about how far the challenges faced by
      low-income countries are the same as those in high-income countries or different.
      We aimed to identify and compare the influences on checklist implementation and
      compliance in the UK and Africa. DESIGN: Ethnographic study involving
      observations, interviews and collection of documents. Thematic analysis of the
      data. SETTING: Operating theatres in one African university hospital and two UK
      university hospitals. PARTICIPANTS: 112 h of observations were undertaken.
      Interviews with 39 theatre and administrative staff were conducted. RESULTS: Many
      staff saw value in the checklist in the UK and African hospitals. Some resentment
      was present in all settings, linked to conflicts between the philosophy behind
      the checklist and the realities of local cultural, social and economic contexts.
      Compliance-involving use, completeness and fidelity-was considerably higher,
      though not perfect, in the UK settings. In these hospitals, compliance was
      supported by established structures and systems, and was not significantly
      undermined by major resource constraints; the same was not true of the low-income
      context. Hierarchical relationships were a major barrier to implementation in all
      settings, but were more marked in the low-income setting. Introducing a checklist
      in a professional environment characterised by a lack of accountability and
      transparency could make the staff feel jeopardised legally, professionally, and
      personally, and it encouraged them to make misleading records of what had
      actually been done. CONCLUSIONS: Surgical checklist implementation is likely to
      be optimised, regardless of the setting, when used as a tool in multifaceted
      cultural and organisational programmes to strengthen patient safety. It cannot be
      assumed that the introduction of a checklist will automatically lead to improved
      communication and clinical processes.

PMID- 23950206
TI  - Clinical response to a lapatinib-based therapy for a Li-Fraumeni syndrome patient
      with a novel HER2V659E mutation.
AB  - Genomic characterization of recurrent breast and lung tumors developed over the
      course of 10 years in a 29-year-old patient with a germline TP53 mutation (Li
      Fraumeni Syndrome) identified oncogenic alterations in the HER2 and EGFR genes
      across all tumors, including HER2 amplifications, an EGFR-exon 20 insertion, and
      the first-in-humans HER2V659E mutation showing a phenotypic convergent evolution
      toward HER2 and EGFR alterations. Following the identification of HER2-activating
      events in the most recent lung carcinoma and in circulating tumor cells, we
      treated the reminiscent metastatic lesions with a lapatinib-based therapy. A
      symptomatic and radiologic clinical response was achieved. HER2V659E sensitivity
      to lapatinib was confirmed in the laboratory. SIGNIFICANCE: The precise knowledge
      of the genomic alterations present in tumors is critical to selecting the optimal
      treatment for each patient. Here, we report the molecular characterization and
      clinical response to a lapatinib-based therapy for the tumors of a Li-Fraumeni
      patient showing prevalence of HER2 and EGFR genomic alterations.

PMID- 23950208
TI  - Cetuximab attenuates its cytotoxic and radiosensitizing potential by inducing
      fibronectin biosynthesis.
AB  - Inherent and acquired resistance to targeted therapeutics continues to emerge as
      a major clinical obstacle. For example, resistance to EGF receptor targeting
      occurs commonly, more so than was expected, on the basis of preclinical work.
      Given emerging evidence that cancer cell-substrate interactions are important
      determinants of therapeutic sensitivity, we examined the impact of cell
      fibronectin interactions on the efficacy of the EGF receptor antibody cetuximab,
      which is used widely for lung cancer treatment. Our results revealed the
      potential for cell-fibronectin interactions to induce radioresistance of human
      non-small cell lung cancer cells. Cell adhesion to fibronectin enhanced tumor
      cell radioresistance and attenuated the cytotoxic and radiosensitizing effects of
      cetuximab. Both in vitro and in vivo, we found that cetuximab treatment led to a
      remarkable induction of fibronectin biosynthesis. Mechanistic analyses revealed
      the induction was mediated by a p38-MAPK-ATF2 signaling pathway and that RNAi
      mediated inhibition of fibronectin could elevate the cytotoxic and
      radiosensitizing potential of cetuximab. Taken together, our findings show how
      cell adhesion blunts cetuximab, which, by inducing fibronectin, generates a self
      attenuating mechanism of drug resistance.

PMID- 23950209
TI  - BRD4 sustains melanoma proliferation and represents a new target for epigenetic
      therapy.
AB  - Metastatic melanoma remains a mostly incurable disease. Although newly approved
      targeted therapies are efficacious in a subset of patients, resistance and
      relapse rapidly ensue. Alternative therapeutic strategies to manipulate
      epigenetic regulators and disrupt the transcriptional program that maintains
      tumor cell identity are emerging. Bromodomain and extraterminal domain (BET)
      proteins are epigenome readers known to exert key roles at the interface between
      chromatin remodeling and transcriptional regulation. Here, we report that BRD4, a
      BET family member, is significantly upregulated in primary and metastatic
      melanoma tissues compared with melanocytes and nevi. Treatment with BET
      inhibitors impaired melanoma cell proliferation in vitro and tumor growth and
      metastatic behavior in vivo, effects that were mostly recapitulated by individual
      silencing of BRD4. RNA sequencing of BET inhibitor-treated cells followed by Gene
      Ontology analysis showed a striking impact on transcriptional programs
      controlling cell growth, proliferation, cell-cycle regulation, and
      differentiation. In particular, we found that, rapidly after BET displacement,
      key cell-cycle genes (SKP2, ERK1, and c-MYC) were downregulated concomitantly
      with the accumulation of cyclin-dependent kinase (CDK) inhibitors (p21 and p27),
      followed by cell-cycle arrest. Importantly, BET inhibitor efficacy was not
      influenced by BRAF or NRAS mutational status, opening the possibility of using
      these small-molecule compounds to treat patients for whom no effective targeted
      therapy exists. Collectively, our study reveals a critical role for BRD4 in
      melanoma tumor maintenance and renders it a legitimate and novel target for
      epigenetic therapy directed against the core transcriptional program of melanoma.

PMID- 23950210
TI  - MicroRNA-218 inhibits glioma invasion, migration, proliferation, and cancer stem
      like cell self-renewal by targeting the polycomb group gene Bmi1.
AB  - Malignant gliomas are the most common central nervous system tumors and the
      molecular mechanism driving their development and recurrence is still largely
      unknown, limiting the treatment of this disease. Here, we show that restoring the
      expression of miR-218, a microRNA commonly downregulated in glioma, dramatically
      reduces the migration, invasion, and proliferation of glioma cells. Quantitative
      reverse transcription PCR and Western blotting analysis revealed that expression
      of the stem cell-promoting oncogene Bmi1 was decreased after overexpression of
      miR-218 in glioma cells. Mechanistic investigations defined Bmi1 as a functional
      downstream target of miR-218 through which miR-218 ablated cell migration and
      proliferation. We documented that miR-218 also blocked the self-renewal of glioma
      stem-like cells, consistent with the suggested role of Bmi1 in stem cell growth.
      Finally, we showed that miR-218 regulated a broad range of genes involved in
      glioma cell development, including Wnt pathways that suppress glioma cell stem
      like qualities. Taken together, our findings reveal miR-218 as a tumor suppressor
      that prevents migration, invasion, proliferation, and stem-like qualities in
      glioma cells.

PMID- 23950212
TI  - Intraindividual variation in one-carbon metabolism plasma biomarkers.
AB  - Interest in the relationship between one-carbon metabolism (OCM) and
      carcinogenesis is intensifying, leading to increased use of related biomarkers as
      measures of exposure. Little is known, however, about the intraindividual
      variation in these markers and whether or not the use of a single measure is
      appropriate for assessing exposure-disease relationships in epidemiologic
      studies. We evaluated the intraindividual variation in plasma concentrations of
      19 OCM biomarkers in a sample of 147 African American and 68 non-Hispanic white
      participants from the Southern Community Cohort Study who donated blood samples
      and responded to questionnaires at two time points from 2005 to 2008. Weighted
      kappa coefficients (kappa) were calculated to assess the agreement between
      quartile assignments based on the repeated measures. Adjusted intraclass
      correlation coefficients (ICC) were also used to assess the consistency of the
      two measurements. Most (16/19) OCM biomarkers showed a moderate or better
      agreement for quartile assignment at the two time points, with only methionine,
      methionine sulfoxide, and cystathionine having kappa <= 0.40. The median-adjusted
      ICC across the 19 biomarkers was 0.60. Reproducibility was highest for flavin
      mononucleotide [ICC = 0.84, 95% confidence interval (CI), 0.79-0.87] and lowest
      for methionine and its oxidative product methionine sulfoxide (ICC = 0.22, 95% CI
      0.09-0.34; ICC = 0.20, 95% CI 0.07-0.32, respectively). Overall, the
      intraindividual variation in OCM biomarkers was similar for African Americans and
      whites and for males and females. Our results suggest that with the exception of
      methionine and methionine sulfoxide, OCM biomarkers generally have good
      intraindividual reproducibility and can be considered as reliable exposure
      measures in epidemiologic studies.

PMID- 23950211
TI  - miR-153 supports colorectal cancer progression via pleiotropic effects that
      enhance invasion and chemotherapeutic resistance.
AB  - Although microRNAs (miRNA) have been broadly studied in cancer, comparatively
      less is understood about their role in progression. Here we report that miR-153
      has a dual role during progression of colorectal cancer by enhancing cellular
      invasiveness and platinum-based chemotherapy resistance. miRNA profiling revealed
      that miR-153 was highly expressed in a cellular model of advanced stage
      colorectal cancer. Its upregulation was also noted in primary human colorectal
      cancer compared with normal colonic epithelium and in more advanced colorectal
      cancer stages compared with early stage disease. In colorectal cancer patients
      followed for 50 months, 21 of 30 patients with high levels of miR-153 had disease
      progression compared with others in this group with low levels of miR-153.
      Functional studies revealed that miR-153 upregulation increased colorectal cancer
      invasiveness and resistance to oxaliplatin and cisplatin both in vitro and in
      vivo. Mechanistic investigations indicated that miR-153 promoted invasiveness
      indirectly by inducing matrix metalloprotease enzyme 9 production, whereas drug
      resistance was mediated directly by inhibiting the Forkhead transcription factor
      Forkhead box O3a (FOXO3a). In support of the latter finding, we found that levels
      of miR-153 and FOXO3a were inversely correlated in matched human colorectal
      cancer specimens. Our findings establish key roles for miR-153 overexpression in
      colorectal cancer progression, rationalizing therapeutic strategies to target
      expression of this miRNA for colorectal cancer treatment.

PMID- 23950213
TI  - Reproductive factors, heterogeneity, and breast tumor subtypes in women of
      mexican descent.
AB  - BACKGROUND: Published data support the presence of etiologic heterogeneity by
      breast tumor subtype, but few studies have assessed this in Hispanic populations.
      METHODS: We assessed tumor subtype prevalence and associations between
      reproductive factors and tumor subtypes in 1,041 women of Mexican descent
      enrolled in a case-only, binational breast cancer study. Multinomial logistic
      regression comparing HER2(+) tumors and triple-negative breast cancer (TNBC) to
      luminal A tumors was conducted. RESULTS: Compared with women with luminal A
      tumors, those with a later age at first pregnancy were less likely to have TNBC
      [OR, 0.61; 95% confidence interval (CI), 0.39-0.95], whereas those with three or
      more full-term pregnancies were more likely to have TNBC (OR, 1.68; 95% CI, 1.10
      2.55). A lower odds of TNBC was shown for longer menstruation duration, whether
      before first pregnancy (OR, 0.78; 95% CI, 0.65-0.93 per 10 years) or menopause
      (OR, 0.79; 95% CI, 0.69-0.91 per 10 years). Patients who reported breastfeeding
      for more than 12 months were over twice as likely to have TNBC than luminal A
      tumors (OR, 2.14; 95% CI, 1.24-3.68). Associations comparing HER2(+) with luminal
      A tumors were weak or nonexistent except for the interval between last full-term
      pregnancy and breast cancer diagnosis. CONCLUSIONS: Findings show etiologic
      heterogeneity by tumor subtype in a population of Hispanic women with unique
      reproductive profiles. IMPACT: Identification of etiologically distinct breast
      tumor subtypes can further improve our understanding of the disease and help
      provide personalized prevention and treatment regimens.

PMID- 23950214
TI  - Melanoma genetic counseling and test reporting improve screening adherence among
      unaffected carriers 2 years later.
AB  - BACKGROUND: A major goal of predictive genetic testing for melanoma is to promote
      early detection to reduce mortality. This study evaluated the long-term impact of
      melanoma genetic test reporting and counseling on screening adherence. METHODS:
      This study assessed adherence to recommendations for annual total body skin
      examinations (TBSE) and monthly skin self-examinations (SSE) among 37 members of
      Utah CDKN2A/p16 kindreds (10 unaffected carriers, 11 affected carriers, and 16
      unaffected noncarriers; response rate = 64.9% of eligible participants). RESULTS:
      Two years following test reporting, adherence to annual TBSE among unaffected
      carriers increased from 40% to 70%. However, unaffected noncarriers' adherence
      decreased from 56% to 13%. Affected carriers reported TBSEs at both assessments
      (91% and 82%, respectively). Monthly SSE frequency remained highly variable in
      all patient groups: at 2 years, 29.7% reported monthly SSEs, 27.0% reported more
      frequent self-examinations, and 43.2% reported underscreening. However, SSE
      quality improved significantly: participants checked more body sites at 2 years
      than at baseline, especially feet, shoulders, legs, and genitals. Perceived
      logistic barriers to TBSEs (e.g., expensive, inconvenient) and SSEs (hard to
      remember, time-consuming) predicted lower adherence. CONCLUSIONS: Unaffected
      carriers reported increased TBSE adherence and thoroughness of SSEs 2 years
      following melanoma genetic test reporting, suggesting clinical benefit in this
      modest sample. Unaffected noncarriers reported comparable gains in SSE
      thoroughness, but decreased TBSEs. IMPACT: Melanoma genetic counseling and test
      reporting may improve adherence among unaffected carrier members of p16 families.
      Further interventions to reduce logistic barriers and to promote continued
      screening adherence among unaffected noncarrier family members may be needed.

PMID- 23950216
TI  - Fecal miR-106a is a useful marker for colorectal cancer patients with false
      negative results in immunochemical fecal occult blood test.
AB  - BACKGROUND: Immunochemical fecal occult blood test (iFOBT) is widely used for
      colorectal cancer screening; however, its sensitivity is insufficient. We
      recently reported a fecal microRNA (miRNA) test (FmiRT) to detect colorectal
      cancer. In this study, we investigated a new colorectal cancer screening method
      combining iFOBT and FmiRT to improve the sensitivity compared with iFOBT alone.
      METHODS: In total, 117 colorectal cancer patients and 107 healthy volunteers were
      enrolled. Ten-milligram fecal samples were collected and iFOBT was conducted.
      Fecal RNA was extracted from residuum of iFOBT and then the expression of 14
      kinds of miRNA was analyzed for the FmiRT using real-time reverse transcription
      PCR. RESULTS: Levels of fecal miR-106a expression in iFOBT+ patients and iFOBT-
      patients were significantly higher than in healthy volunteers (P = 0.001). The
      sensitivity and specificity of FmiRT using miR-106a were 34.2% and 97.2%, and
      those of iFOBT were 60.7% and 98.1%, respectively. The overall sensitivity and
      specificity of the new screening method combining iFOBT and FmiRT were 70.9% and
      96.3%, respectively. One quarter of colorectal cancer patients with false
      negative iFOBT seemed to be true positive upon adding FmiRT using fecal miR-106a.
      CONCLUSIONS: Fecal miR-106a is a good molecular marker to identify colorectal
      cancer patients from among those with negative iFOBT results. FmiRT combined with
      iFOBT may improve the sensitivity to detect colorectal cancer. IMPACT: We have
      shown the usefulness of fecal miR-106a to detect the colorectal cancer patients
      among those with negative iFOBT results.

PMID- 23950215
TI  - Parental tobacco and alcohol use and risk of hepatoblastoma in offspring: a
      report from the children's oncology group.
AB  - BACKGROUND: Hepatoblastoma is a rare pediatric liver tumor that has significantly
      increased in incidence over the last several decades. The International Agency
      for Research on Cancer (IARC) recently classified hepatoblastoma as a tobacco
      related cancer. Parental alcohol use has shown no association. We examined
      associations between parental tobacco and alcohol use around the time of
      pregnancy and hepatoblastoma in a large case-control study. METHODS: Maternal
      interviews were completed for 383 cases diagnosed in the United States during
      2000-2008. Controls (n = 387) were identified through U.S. birth registries and
      frequency-matched to cases on birth weight, birth year, and region of residence.
      We used unconditional logistic regression to calculate ORs and 95% confidence
      intervals (CI) for associations between parental smoking and maternal drinking
      and offspring hepatoblastoma. RESULTS: We found no association between
      hepatoblastoma and maternal smoking at any time (OR, 1.0; 95% CI, 0.7-1.4),
      within the year before pregnancy (OR, 1.1; 95% CI, 0.8-1.6), early in pregnancy
      (OR, 1.0; 95% CI, 0.7-1.6), or throughout pregnancy (OR, 0.9; 95% CI, 0.5-1.6).
      We observed marginally positive associations between hepatoblastoma and paternal
      smoking in the year before pregnancy (OR, 1.4; 95% CI, 1.0-2.0) and during
      pregnancy (OR, 1.4; 95% CI, 0.9-2.0). Maternal alcohol use was not associated
      with hepatoblastoma. CONCLUSION: Our results do not provide evidence for an
      etiologic relationship between maternal smoking or drinking and hepatoblastoma,
      and only weak evidence for an association for paternal smoking in the year before
      pregnancy. IMPACT: Our study provides limited support for hepatoblastoma as a
      tobacco-related cancer; however, it remains wise to counsel prospective parents
      on the merits of smoking cessation.

PMID- 23950217
TI  - Clostridium difficile--special collection.

PMID- 23950218
TI  - Importance of UDP-glucuronosyltransferase 1A1 expression in skin and its
      induction by UVB in neonatal hyperbilirubinemia.
AB  - UDP-glucuronosyltransferase (UGT) 1A1 is the sole enzyme that can metabolize
      bilirubin. Human infants physiologically develop hyperbilirubinemia as the result
      of inadequate expression of UGT1A1 in the liver. Although phototherapy using blue
      light is effective in preventing jaundice, sunlight has also been suggested, but
      without conclusive evidence, to reduce serum bilirubin levels. We investigated
      the mRNA expression pattern of human UGT1A1 in human skin, human skin
      keratinocyte (HaCaT) cells, and skin of humanized UGT1 mice. The effects of UVB
      irradiation on the expression of UGT1A1 in the HaCaT cells were also examined.
      Multiple UGT1A isoforms, including UGT1A1, were expressed in human skin and HaCaT
      cells. When HaCaT cells were treated with UVB-exposed tryptophan, UGT1A1 mRNA and
      activity were significantly induced. Treatment of the HaCaT cells with 6
      formylindolo[3,2-b]carbazole, which is one of the tryptophan derivatives formed
      by UVB, resulted in an induction of UGT1A1 mRNA and activity. In neonates, the
      expression of UGT1A1 was greater in the skin; in adults, UGT1A1 was expressed
      mainly in the liver. Treatment of humanized UGT1 mice with UVB resulted in a
      reduction of serum bilirubin levels, along with increased UGT1A1 expression and
      activity in the skin. Our data revealed a protective role of UGT1A1 expressed in
      the skin against neonatal hyperbilirubinemia. Sunlight, a natural and free source
      of light, makes it possible to treat neonatal jaundice while allowing mothers to
      breast-feed neonates. 

PMID- 23950219
TI  - Functional validation of virtual screening for novel agents with general
      anesthetic action at ligand-gated ion channels.
AB  - GABA(A) receptors play a crucial role in the actions of general anesthetics. The
      recently published crystal structure of the general anesthetic propofol bound to
      Gloeobacter violaceus ligand-gated ion channel (GLIC), a bacterial homolog of
      GABA(A) receptors, provided an opportunity to explore structure-based ligand
      discovery for pentameric ligand-gated ion channels (pLGICs). We used molecular
      docking of 153,000 commercially available compounds to identify molecules that
      interact with the propofol binding site in GLIC. In total, 29 compounds were
      selected for functional testing on recombinant GLIC, and 16 of these compounds
      modulated GLIC function. Active compounds were also tested on recombinant GABA(A)
      receptors, and point mutations around the presumed binding pocket were introduced
      into GLIC and GABA(A) receptors to test for binding specificity. The potency of
      active compounds was only weakly correlated with properties such as lipophilicity
      or molecular weight. One compound was found to mimic the actions of propofol on
      GLIC and GABA(A), and to be sensitive to mutations that reduce the action of
      propofol in both receptors. Mutant receptors also provided insight about the
      position of the binding sites and the relevance of the receptor's conformation
      for anesthetic actions. Overall, the findings support the feasibility of the use
      of virtual screening to discover allosteric modulators of pLGICs, and suggest
      that GLIC is a valid model system to identify novel GABA(A) receptor ligands.

PMID- 23950220
TI  - Effect of temperature on photosynthesis and growth in marine Synechococcus spp.
AB  - In this study, we develop a mechanistic understanding of how temperature affects
      growth and photosynthesis in 10 geographically and physiologically diverse
      strains of Synechococcus spp. We found that Synechococcus spp. are able to
      regulate photochemistry over a range of temperatures by using state transitions
      and altering the abundance of photosynthetic proteins. These strategies minimize
      photosystem II (PSII) photodamage by keeping the photosynthetic electron
      transport chain (ETC), and hence PSII reaction centers, more oxidized. At
      temperatures that approach the optimal growth temperature of each strain when
      cellular demand for reduced nicotinamide adenine dinucleotide phosphate (NADPH)
      is greatest, the phycobilisome (PBS) antenna associates with PSII, increasing the
      flux of electrons into the ETC. By contrast, under low temperature, when slow
      growth lowers the demand for NADPH and linear ETC declines, the PBS associates
      with photosystem I. This favors oxidation of PSII and potential increase in
      cyclic electron flow. For Synechococcus sp. WH8102, growth at higher temperatures
      led to an increase in the abundance of PBS pigment proteins, as well as higher
      abundance of subunits of the PSII, photosystem I, and cytochrome b6f complexes.
      This would allow cells to increase photosynthetic electron flux to meet the
      metabolic requirement for NADPH during rapid growth. These PBS-based temperature
      acclimation strategies may underlie the larger geographic range of this group
      relative to Prochlorococcus spp., which lack a PBS. 

PMID- 23950221
TI  - Engineered knottin peptide enables noninvasive optical imaging of intracranial
      medulloblastoma.
AB  - Central nervous system tumors carry grave clinical prognoses due to limited
      effectiveness of surgical resection, radiation, and chemotherapy. Thus, improved
      strategies for brain tumor visualization and targeted treatment are critically
      needed. We demonstrate that mouse cerebellar medulloblastoma (MB) can be targeted
      and illuminated with a fluorescent, engineered cystine knot (knottin) peptide
      that binds with high affinity to alphavbeta3, alphavbeta5, and alpha5beta1
      integrin receptors. This integrin-binding knottin peptide, denoted EETI 2.5F, was
      evaluated as a molecular imaging probe in both orthotopic and genetic models of
      MB. Following tail vein injection, fluorescence arising from dye-conjugated EETI
      2.5F was localized to the tumor compared with the normal surrounding brain
      tissue, as measured by optical imaging. The imaging signal intensity correlated
      with tumor volume. Due to its unique ability to bind to alpha5beta1 integrin,
      EETI 2.5F showed superior in vivo and ex vivo brain tumor imaging contrast
      compared with other engineered integrin-binding knottin peptides and with
      c(RGDfK), a well-studied integrin-binding peptidomimetic. Next, EETI 2.5F was
      fused to an antibody fragment crystallizable (Fc) domain (EETI 2.5F-Fc) to
      determine if a larger integrin-binding protein could also target intracranial
      brain tumors. EETI 2.5F-Fc, conjugated to a fluorescent dye, illuminated MB
      following i.v. injection and was able to distribute throughout the tumor
      parenchyma. In contrast, brain tumor imaging signals were not detected in mice
      injected with EETI 2.5F proteins containing a scrambled integrin-binding
      sequence, demonstrating the importance of target specificity. These results
      highlight the potential of using EETI 2.5F and EETI 2.5-Fc as targeted molecular
      probes for brain tumor imaging. 

PMID- 23950222
TI  - Structure of the YajR transporter suggests a transport mechanism based on the
      conserved motif A.
AB  - The major facilitator superfamily (MFS) is the largest family of secondary active
      transporters and is present in all life kingdoms. Detailed structural basis of
      the substrate transport and energy-coupling mechanisms of these proteins remain
      to be elucidated. YajR is a putative proton-driven MFS transporter found in many
      Gram-negative bacteria. Here we report the crystal structure of Escherichia coli
      YajR at 3.15 A resolution in an outward-facing conformation. In addition to
      having the 12 canonical transmembrane helices, the YajR structure includes a
      unique 65-residue C-terminal domain which is independently stable. The structure
      is unique in illustrating the functional role of "sequence motif A." This highly
      conserved element is seen to stabilize the outward conformation of YajR and
      suggests a general mechanism for the conformational change between the inward and
      outward states of the MFS transporters. 

PMID- 23950223
TI  - Glucocorticoid receptor represses proinflammatory genes at distinct steps of the
      transcription cycle.
AB  - Widespread anti-inflammatory actions of glucocorticoid hormones are mediated by
      the glucocorticoid receptor (GR), a ligand-dependent transcription factor of the
      nuclear receptor superfamily. In conjunction with its corepressor GR-interacting
      protein-1 (GRIP1), GR tethers to the DNA-bound activator protein-1 and NF-kappaB
      and represses transcription of their target proinflammatory cytokine genes.
      However, these target genes fall into distinct classes depending on the step of
      the transcription cycle that is rate-limiting for their activation: Some are
      controlled through RNA polymerase II (PolII) recruitment and initiation, whereas
      others undergo signal-induced release of paused elongation complexes into
      productive RNA synthesis. Whether these genes are differentially regulated by GR
      is unknown. Here we report that, at the initiation-controlled inflammatory genes
      in primary macrophages, GR inhibited LPS-induced PolII occupancy. In contrast, at
      the elongation-controlled genes, GR did not affect PolII recruitment or
      transcription initiation but promoted, in a GRIP1-dependent manner, the
      accumulation of the pause-inducing negative elongation factor. Consistently, GR
      dependent repression of elongation-controlled genes was abolished specifically in
      negative elongation factor-deficient macrophages. Thus, GR:GRIP1 use distinct
      mechanisms to repress inflammatory genes at different stages of the transcription
      cycle. 

PMID- 23950224
TI  - Efficient discovery of overlapping communities in massive networks.
AB  - Detecting overlapping communities is essential to analyzing and exploring natural
      networks such as social networks, biological networks, and citation networks.
      However, most existing approaches do not scale to the size of networks that we
      regularly observe in the real world. In this paper, we develop a scalable
      approach to community detection that discovers overlapping communities in massive
      real-world networks. Our approach is based on a Bayesian model of networks that
      allows nodes to participate in multiple communities, and a corresponding
      algorithm that naturally interleaves subsampling from the network and updating an
      estimate of its communities. We demonstrate how we can discover the hidden
      community structure of several real-world networks, including 3.7 million US
      patents, 575,000 physics articles from the arXiv preprint server, and 875,000
      connected Web pages from the Internet. Furthermore, we demonstrate on large
      simulated networks that our algorithm accurately discovers the true community
      structure. This paper opens the door to using sophisticated statistical models to
      analyze massive networks. 

PMID- 23950493
TI  - Oxidative stress and ageing of the post-ovulatory oocyte.
AB  - With extended periods of time following ovulation, the metaphase II stage oocyte
      experiences deterioration in quality referred to as post-ovulatory oocyte ageing.
      Post-ovulatory ageing occurs both in vivo and in vitro and has been associated
      with reduced fertilization rates, poor embryo quality, post-implantation errors
      and abnormalities in the offspring. Although the physiological consequences of
      post-ovulatory oocyte ageing have largely been established, the molecular
      mechanisms controlling this process are not well defined. This review analyses
      the relationships between biochemical changes exhibited by the ageing oocyte and
      the symptoms associated with the ageing phenotype. We also discuss molecular
      events that are potentially involved in orchestrating post-ovulatory ageing with
      a particular focus on the role of oxidative stress. We propose that oxidative
      stress may act as the initiator for a cascade of events that create the aged
      oocyte phenotype. Specifically, oxidative stress has the capacity to cause a
      decline in levels of critical cell cycle factors such as maturation-promoting
      factor, impair calcium homoeostasis, induce mitochondrial dysfunction and
      directly damage multiple intracellular components of the oocyte such as lipids,
      proteins and DNA. Finally, this review addresses current strategies for delaying
      post-ovulatory oocyte ageing with a particular focus on the potential use of
      compounds such as caffeine or selected antioxidants in the development of more
      refined media for the preservation of oocyte integrity during IVF procedures. 

PMID- 23950225
TI  - Priming the brain to capitalize on metaplasticity in stroke rehabilitation.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is emerging as a potentially
      valuable intervention to augment the effects of behavioral therapy for stroke.
      When used in conjunction with other therapies, rTMS embraces the concept of
      metaplasticity. Due to homeostatic mechanisms inherent to metaplasticity,
      interventions known to be in isolation to enhance excitability can interact when
      applied successively under certain timing conditions and produce enhanced or
      opposite effects. Similar to "muscular wisdom," with its self-protective
      mechanisms, there also appears to be "synaptic wisdom" in neural networks with
      homeostatic processes that prevent over- and under-excitability. These processes
      have implications for both enhancing and suppressing the excitability effects
      from behavioral therapy. The purpose of this article is to relate the concept of
      metaplasticity, as derived from studies in humans who are healthy, to stroke
      rehabilitation and consider how it can be leveraged to maximize stroke outcomes. 

PMID- 23950494
TI  - Pou5f1 transcription factor controls zygotic gene activation in vertebrates.
AB  - The development of multicellular animals is initially controlled by maternal gene
      products deposited in the oocyte. During the maternal-to-zygotic transition,
      transcription of zygotic genes commences, and developmental control starts to be
      regulated by zygotic gene products. In Drosophila, the transcription factor Zelda
      specifically binds to promoters of the earliest zygotic genes and primes them for
      activation. It is unknown whether a similar regulation exists in other animals.
      We found that zebrafish Pou5f1, a homolog of the mammalian pluripotency
      transcription factor Oct4, occupies SOX-POU binding sites before the onset of
      zygotic transcription and activates the earliest zygotic genes. Our data position
      Pou5f1 and SOX-POU sites at the center of the zygotic gene activation network of
      vertebrates and provide a link between zygotic gene activation and pluripotency
      control. 

PMID- 23950495
TI  - Slow earthquakes, preseismic velocity changes, and the origin of slow frictional
      stick-slip.
AB  - Earthquakes normally occur as frictional stick-slip instabilities, resulting in
      catastrophic failure and seismic rupture. Tectonic faults also fail in slow
      earthquakes with rupture durations of months or more, yet their origin is poorly
      understood. Here, we present laboratory observations of repetitive, slow stick
      slip in serpentinite fault zones and mechanical evidence for their origin. We
      document a transition from unstable to stable frictional behavior with increasing
      slip velocity, providing a mechanism to limit the speed of slow earthquakes. We
      also document reduction of P-wave speed within the active shear zone before stick
      slip events. If similar mechanisms operate in nature, our results suggest that
      higher-resolution studies of elastic properties in tectonic fault zones may aid
      in the search for reliable earthquake precursors. 

PMID- 23950496
TI  - Reversibly assembled cellular composite materials.
AB  - We introduce composite materials made by reversibly assembling a three
      dimensional lattice of mass-produced carbon fiber-reinforced polymer composite
      parts with integrated mechanical interlocking connections. The resulting cellular
      composite materials can respond as an elastic solid with an extremely large
      measured modulus for an ultralight material (12.3 megapascals at a density of 7.2
      milligrams per cubic centimeter). These materials offer a hierarchical
      decomposition in modeling, with bulk properties that can be predicted from
      component measurements and deformation modes that can be determined by the
      placement of part types. Because site locations are locally constrained,
      structures can be produced in a relative assembly process that merges desirable
      features of fiber composites, cellular materials, and additive manufacturing. 

PMID- 23950499
TI  - The road to pollinator health.

PMID- 23950497
TI  - Dynamically reshaping signaling networks to program cell fate via genetic
      controllers.
AB  - Engineering of cell fate through synthetic gene circuits requires methods to
      precisely implement control around native decision-making pathways and offers the
      potential to direct cell processes. We demonstrate a class of genetic control
      systems, molecular network diverters, that interface with a native signaling
      pathway to route cells to divergent fates in response to environmental signals
      without modification of native genetic material. A method for identifying control
      points within natural networks is described that enables the construction of
      synthetic control systems that activate or attenuate native pathways to direct
      cell fate. We integrate opposing genetic programs by developing network
      architectures for reduced antagonism and demonstrate rational tuning of
      performance. Extension of these control strategies to mammalian systems should
      facilitate the engineering of complex cellular signaling systems. 

PMID- 23950498
TI  - Caffeoyl shikimate esterase (CSE) is an enzyme in the lignin biosynthetic pathway
      in Arabidopsis.
AB  - Lignin is a major component of plant secondary cell walls. Here we describe
      caffeoyl shikimate esterase (CSE) as an enzyme central to the lignin biosynthetic
      pathway. Arabidopsis thaliana cse mutants deposit less lignin than do wild-type
      plants, and the remaining lignin is enriched in p-hydroxyphenyl units. Phenolic
      metabolite profiling identified accumulation of the lignin pathway intermediate
      caffeoyl shikimate in cse mutants as compared to caffeoyl shikimate levels in the
      wild type, suggesting caffeoyl shikimate as a substrate for CSE. Accordingly,
      recombinant CSE hydrolyzed caffeoyl shikimate into caffeate. Associated with the
      changes in lignin, the conversion of cellulose to glucose in cse mutants
      increased up to fourfold as compared to that in the wild type upon
      saccharification without pretreatment. Collectively, these data necessitate the
      revision of currently accepted models of the lignin biosynthetic pathway. 

PMID- 23950503
TI  - Epidemiology. Budget woes threaten long-term heart studies.

PMID- 23950504
TI  - Emerging diseases. Researchers scramble to understand camel connection to MERS.

PMID- 23950505
TI  - Social science. Senator's demands freeze NSF political science grants.

PMID- 23950506
TI  - Particle physics. Europe aims for a cut-rate superlaser to power future particle
      accelerators.

PMID- 23950507
TI  - New team, old hands.

PMID- 23950508
TI  - The women of the Cosmos Club.

PMID- 23950510
TI  - Astronomy. The Crab that roared.

PMID- 23950509
TI  - Solar system exploration. Pluto, the last planetary first.

PMID- 23950511
TI  - Develop, then intensify.

PMID- 23950512
TI  - The systematic place of morals in markets.

PMID- 23950513
TI  - The systematic place of morals in markets--response.

PMID- 23950515
TI  - Global food supply. Reevaluate pesticides for food security and safety.

PMID- 23950516
TI  - Social science. A U.K. view on the U.S. attack on social sciences.

PMID- 23950517
TI  - Molecular biology. Long noncoding RNAs Xist in three dimensions.

PMID- 23950518
TI  - Geophysics. Gauging Greenland's subglacial water.

PMID- 23950519
TI  - Epidemiology. Paths from pesticides to Parkinson's.

PMID- 23950520
TI  - Geophysics. Earthquake risk in Turkey.

PMID- 23950521
TI  - Applied physics. Triggering an optical transistor with one photon.

PMID- 23950522
TI  - Neuroscience. Mapping neuronal diversity one cell at a time.

PMID- 23950523
TI  - Smarter pest control. The pesticide paradox. Introduction.

PMID- 23950524
TI  - Infographic: pesticide planet.

PMID- 23950525
TI  - A lethal dose of RNA.

PMID- 23950526
TI  - The war against weeds down under.

PMID- 23950527
TI  - Vietnam turns back a 'tsunami of pesticides'.

PMID- 23950528
TI  - In rural Asia, locking up poisons to prevent suicides.

PMID- 23950529
TI  - Growing up with pesticides.

PMID- 23950530
TI  - Current challenges and trends in the discovery of agrochemicals.
AB  - Crop protection chemistry has come a long way from its "alchemic" beginnings in
      the late 19th century to a high-tech science that supports the sustainable
      production of food, feed, and fiber for a rapidly growing population. Cutting
      edge developments in the design and synthesis of agrochemicals help to tackle
      today's challenges of weed and pest resistance, higher regulatory safety margins,
      and higher cost of goods with the invention of selective, environmentally benign,
      low use rate, and cost-effective active ingredients. 

PMID- 23950531
TI  - Pivoting the plant immune system from dissection to deployment.
AB  - Diverse and rapidly evolving pathogens cause plant diseases and epidemics that
      threaten crop yield and food security around the world. Research over the last 25
      years has led to an increasingly clear conceptual understanding of the molecular
      components of the plant immune system. Combined with ever-cheaper DNA-sequencing
      technology and the rich diversity of germ plasm manipulated for over a century by
      plant breeders, we now have the means to begin development of durable (long
      lasting) disease resistance beyond the limits imposed by conventional breeding
      and in a manner that will replace costly and unsustainable chemical controls. 

PMID- 23950532
TI  - Evaluating pesticide degradation in the environment: blind spots and emerging
      opportunities.
AB  - The benefits of global pesticide use come at the cost of their widespread
      occurrence in the environment. An array of abiotic and biotic transformations
      effectively removes pesticides from the environment, but may give rise to
      potentially hazardous transformation products. Despite a large body of pesticide
      degradation data from regulatory testing and decades of pesticide research, it
      remains difficult to anticipate the extent and pathways of pesticide degradation
      under specific field conditions. Here, we review the major scientific challenges
      in doing so and discuss emerging opportunities to identify pesticide degradation
      processes in the field. 

PMID- 23950533
TI  - Wildlife ecotoxicology of pesticides: can we track effects to the population
      level and beyond?
AB  - During the past 50 years, the human population has more than doubled and global
      agricultural production has similarly risen. However, the productive arable area
      has increased by just 10%; thus the increased use of pesticides has been a
      consequence of the demands of human population growth, and its impact has reached
      global significance. Although we often know a pesticide's mode of action in the
      target species, we still largely do not understand the full impact of unintended
      side effects on wildlife, particularly at higher levels of biological
      organization: populations, communities, and ecosystems. In these times of
      regional and global species declines, we are challenged with the task of causally
      linking knowledge about the molecular actions of pesticides to their possible
      interference with biological processes, in order to develop reliable predictions
      about the consequences of pesticide use, and misuse, in a rapidly changing world.

PMID- 23950534
TI  - Incision into the eastern Andean Plateau during Pliocene cooling.
AB  - Canyon incision into mountain topography is commonly used as a proxy for surface
      uplift driven by tectonic or geodynamic processes, but climatic changes can also
      instigate incision. The ~1250-kilometer (km)-long eastern margin of the Andean
      Plateau hosts a series of 1.5- to 2.5-km-deep canyons that cross major
      deformation zones. Using (U-Th)/He thermochronology, we document a transition
      from Miocene faulting to Pliocene canyon incision across the northeastern plateau
      margin. Regionally, widespread Pliocene incision into the eastern plateau margin
      is concurrent with a shift in global climate from early Pliocene warmth to late
      Pliocene cooling. Enhanced moisture transport onto the Andean Plateau driven by
      sea surface temperature changes during cooling is the likely pacemaker for canyon
      incision. 

PMID- 23950535
TI  - Basal drainage system response to increasing surface melt on the Greenland ice
      sheet.
AB  - Surface meltwater reaching the bed of the Greenland ice sheet imparts a
      fundamental control on basal motion. Sliding speed depends on ice/bed coupling,
      dictated by the configuration and pressure of the hydrologic drainage system. In
      situ observations in a four-site transect containing 23 boreholes drilled to
      Greenland's bed reveal basal water pressures unfavorable to water-draining
      conduit development extending inland beneath deep ice. This finding is supported
      by numerical analysis based on realistic ice sheet geometry. Slow meltback of ice
      walls limits conduit growth, inhibiting their capacity to transport increased
      discharge. Key aspects of current conceptual models for Greenland basal
      hydrology, derived primarily from the study of mountain glaciers, appear to be
      limited to a portion of the ablation zone near the ice sheet margin. 

PMID- 23950536
TI  - Earliest evolution of multituberculate mammals revealed by a new Jurassic fossil.
AB  - Multituberculates were successful herbivorous mammals and were more diverse and
      numerically abundant than any other mammal groups in Mesozoic ecosystems. The
      clade also developed diverse locomotor adaptations in the Cretaceous and
      Paleogene. We report a new fossil skeleton from the Late Jurassic of China that
      belongs to the basalmost multituberculate family. Dental features of this new
      Jurassic multituberculate show omnivorous adaptation, and its well-preserved
      skeleton sheds light on ancestral skeletal features of all multituberculates,
      especially the highly mobile joints of the ankle, crucial for later evolutionary
      success of multituberculates in the Cretaceous and Paleogene. 

PMID- 23950539
TI  - Letter from Howard K. Koh.

PMID- 23950538
TI  - A gut lipid messenger links excess dietary fat to dopamine deficiency.
AB  - Excessive intake of dietary fats leads to diminished brain dopaminergic function.
      It has been proposed that dopamine deficiency exacerbates obesity by provoking
      compensatory overfeeding as one way to restore reward sensitivity. However, the
      physiological mechanisms linking prolonged high-fat intake to dopamine deficiency
      remain elusive. We show that administering oleoylethanolamine, a gastrointestinal
      lipid messenger whose synthesis is suppressed after prolonged high-fat exposure,
      is sufficient to restore gut-stimulated dopamine release in high-fat-fed mice.
      Administering oleoylethanolamine to high-fat-fed mice also eliminated motivation
      deficits during flavorless intragastric feeding and increased oral intake of low
      fat emulsions. Our findings suggest that high-fat-induced gastrointestinal
      dysfunctions play a key role in dopamine deficiency and that restoring gut
      generated lipid signaling may increase the reward value of less palatable, yet
      healthier, foods. 

PMID- 23950537
TI  - Cleavage of fibrinogen by proteinases elicits allergic responses through Toll
      like receptor 4.
AB  - Proteinases and the innate immune receptor Toll-like receptor 4 (TLR4) are
      essential for expression of allergic inflammation and diseases such as asthma. A
      mechanism that links these inflammatory mediators is essential for explaining the
      fundamental basis of allergic disease but has been elusive. Here, we demonstrate
      that TLR4 is activated by airway proteinase activity to initiate both allergic
      airway disease and antifungal immunity. These outcomes were induced by proteinase
      cleavage of the clotting protein fibrinogen, yielding fibrinogen cleavage
      products that acted as TLR4 ligands on airway epithelial cells and macrophages.
      Thus, allergic airway inflammation represents an antifungal defensive strategy
      that is driven by fibrinogen cleavage and TLR4 activation. These findings clarify
      the molecular basis of allergic disease and suggest new therapeutic strategies. 

PMID- 23950540
TI  - Promising practices to eliminate tobacco disparities among Asian American, native
      Hawaiian and Pacific Islander communities.
AB  - Tobacco use continues to be the single most preventable cause of death for all
      groups in the United States, including Asian Americans (AAs) and Native Hawaiians
      and Pacific Islanders (NHPIs). Despite efforts in tobacco control over the past
      two decades, tobacco-related health disparities remain in some priority
      population groups, including AAs and NHPIs. This special supplement features
      strategies and promising practices for addressing the critical problem of tobacco
      in the AA and NHPI communities. 

PMID- 23950542
TI  - The value of pilot studies in clinical research: a clinical translation of the
      research article titled "In search of an adult attachment stress provocation to
      measure effect on the oxytocin system".

PMID- 23950541
TI  - In search of an adult attachment stress provocation to measure effect on the
      oxytocin system: a pilot validation study.
AB  - BACKGROUND: Oxytocin is a promising biomarker for psychiatric conditions arising
      from early relational trauma, childhood maltreatment, and attachment
      dysregulation, including posttraumatic stress and dissociative disorders.
      OBJECTIVE: This exploratory pilot study examined plasma oxytocin as a biomarker
      for alterations in the attachment system. DESIGN: We used a single group,
      repeated-measures design with 15 women. The protocol used a film clip previously
      validated as a provocation to the hypothalamic-pituitary-adrenal axis. RESULTS:
      The repeated-measures ANOVA showed differences in oxytocin across the three time
      points. Correlations with oxytocin indicated that measures of dissociation and
      somatization correlated most strongly with higher levels of oxytocin measured
      during exposure to the film's bonding scene and posttraumatic stress disorder
      correlated most strongly with lower levels at the film's abandonment scene. Post
      hoc analyses revealed differences in oxytocin response related to
      psychopathology. CONCLUSION: Replication studies should characterize participants
      on a range of psychiatric conditions associated with attachment dysregulation.

PMID- 23950543
TI  - Competency-based training for PMH nurse generalists: inpatient intervention and
      prevention of suicide.
AB  - Suicide is the tenth leading cause of death in the United States. Approximately
      90,000 psychiatric mental health (PMH) nurse generalists work in hospitals in the
      United States, mostly on inpatient psychiatric units where the most acutely
      suicidal patients are hospitalized. Although competencies have been developed for
      mental health clinicians in assessing and managing suicide risk, there are no
      standard competencies for PMH nurse generalists. Widely accepted nursing
      practices do not meet suicide-specific standards of care or evidence-based
      criteria. Although both the Commission on Collegiate Nursing Education Essentials
      for Baccalaureate Education and the Quality and Safety Education for Nurses
      competencies stress the necessity for comprehensive assessment, safe clinical
      practices, patient-centered care, evidence-based interventions, and
      interprofessional communication and collaboration, there are no specific
      requirements for suicide prevention training in educational and clinical
      programs. The American Psychiatric Nurses Association has an opportunity to
      provide leadership in developing, implementing, and evaluating competency-based
      training for nurses and partner with the national effort to increase the
      competencies in suicide prevention in the behavioral health workforce. 

PMID- 23950544
TI  - Commentary from an author, advocate, and grateful survivor.

PMID- 23950545
TI  - In memory of my brother.

PMID- 23950546
TI  - Developing a culture of mentoring in psychiatric mental health nursing.

PMID- 23950547
TI  - Evidence-based practice: a model for clinical application.
AB  - Health care reform authorized by the Affordable Care Act is based on the belief
      that evidence-based practice (EBP) generates cost savings due to the delivery of
      more effective care. Published meta-analyses and systematic reviews provide
      clear, unbiased evidence on the effectiveness of specific interventions. Yet
      translating the interventions into the practice setting requires additional
      clinical skills and judgments extending beyond the scientific assessment of the
      EBP literature. Effective use of EBP interventions requires clinicians
      effectively answering an additional set of questions specific to the case and
      clinical context. These questions focus on correctly identifying the problem and
      increased level of specificity for any given situation. Using a clinical
      application of the PICO model, the clinician and the patient should be able to
      achieve a higher level of clinical outcomes. 

PMID- 23950548
TI  - Telemental health adoption can change psychiatric-mental health nursing practice.

PMID- 23950549
TI  - The effects of chronic candesartan treatment on cardiac and hepatic adenosine
      monophosphate-activated protein kinase in rats submitted to surgical stress.
AB  - INTRODUCTION: adenosine monophosphate-activated protein kinase (AMPK) plays a
      prominent role as a metabolic stress sensor, and it has recently been suggested
      that the renin-angiotensin system, in addition to its role in stress regulation,
      may play a significant role in regulating the AMPK system. This study aimed to
      evaluate the effects of candesartan, an angiotensin II receptor blocker, on
      cardiac and hepatic AMPK activity basally as well as after surgical stress under
      general anesthesia. MATERIALS AND METHODS: Male Wistar rats were treated with 5
      mg/kg/day candesartan in their drinking water for two weeks. Levels of cardiac
      and hepatic AMPK activity were determined, using a kinase activity assay, basally
      and after surgical stress under general anesthesia. RESULTS: Chronic
      administration of candesartan increased hepatic AMPK activity approximately 4
      times (p<0.05) while no significant change was demonstrated in cardiac AMPK.
      Cardiac and hepatic AMPK activities were not significantly increased by surgical
      stress alone performed under anesthesia. However, chronic treatment with
      candesartan decreased AMPK activity in both liver and heart after surgical stress
      under anesthesia (p<0.01 for both comparisons). CONCLUSIONS: While chronic
      candesartan treatment may stimulate AMPK activity in certain organs such as the
      liver, when combined with surgical stress under anesthesia it inhibits pathways
      regulating AMPK activity.

PMID- 23950550
TI  - Temporal profile of lymphocyte counts and relationship with infections with
      fingolimod therapy.
AB  - BACKGROUND: Reduction in peripheral blood lymphocytes is an expected
      pharmacodynamic outcome of fingolimod therapy. OBJECTIVE: The objective of this
      article is to evaluate lymphocyte dynamics during and after fingolimod therapy
      and assess the relationship between lymphocyte counts and infections. METHODS:
      Lymphocyte counts and their relationship with infections were evaluated in three
      multiple sclerosis (MS) populations: (Group A) FREEDOMS phase 3 core study group
      (n = 1272); (Group B) All Studies group (one phase 2 and two phase 3 studies,
      plus their extensions; n = 2315); and (Group C) Follow-up group (after fingolimod
      discontinuation; n = 538). RESULTS: Administration of fingolimod 0.5 mg led to
      reductions in lymphocyte counts to a steady-state of 24%-30% of baseline values
      within two weeks, which remained stable while on therapy. Following fingolimod
      discontinuation, average counts exceeded the lower limit of normal range within
      six to eight weeks, and were 80% of baseline values by three months. In Group A,
      infection rates per patient-year were 1.4 with placebo and 1.0 in fingolimod
      treated patients who had the lowest lymphocyte counts (< 0.2 * 10(9)/l). No
      evidence was seen for an increase in serious or opportunistic infections.
      CONCLUSIONS: Fingolimod induces a rapid and reversible reduction in lymphocyte
      counts without an increase in infections relative to placebo. Because fingolimod
      reduces blood lymphocyte counts via redistribution in secondary lymphoid organs,
      peripheral blood lymphocyte counts cannot be utilized to evaluate the lymphocyte
      subset status of a patient.

PMID- 23950551
TI  - An overview and categorization of dynamic arm supports for people with decreased
      arm function.
AB  - BACKGROUND: Assistive devices that augment arm function were already introduced
      during the polio era. Devices are still being developed, but a review has not
      been performed thus far. OBJECTIVE: To create an overview and categorize
      assistive devices facilitating arm function in activities of daily living for
      people with decreased arm function. STUDY DESIGN: Literature review. METHODS: A
      systematic review in three scientific literature databases. Conference
      proceedings, assistive technology databases, and references were searched and
      experts consulted. This resulted in a database of dynamic arm supports. Product
      information was added, and the devices were categorized. RESULTS: A total of 104
      dynamic arm supports were found. These could be categorized as nonactuated
      devices (N = 39), passively actuated devices (N = 24), actively actuated devices
      (N = 34), or devices using the functional electrical stimulation principle (N =
      7). Functionality analysis resulted in second-level categorization: tremor
      suppression, facilitation of anti-gravity movement, and assistance of specific
      joint motion. CONCLUSION: All devices could be ordered in a categorization of low
      complexity. Many have been developed; most have disappeared and have been
      succeeded by similar devices. Limitations of the devices found mainly concern
      interfacing and the range of motion facilitated. Future devices could make use of
      whatever residual strength is available in the users' arm for control. CLINICAL
      RELEVANCE: The provided overview of devices in this article and the
      classification developed is relevant for practitioners seeking assistive
      solutions for their clients as it makes the range of developed solutions both
      accessible and comprehensible.

PMID- 23950552
TI  - Treatment stability of Milwaukee brace in idiopathic hyperkyphosis.
AB  - BACKGROUND: The Milwaukee brace is an efficient method for correcting
      hyperkyphosis before skeletal maturity. However, loss of correction in long-term
      follow-up is inevitable. OBJECTIVES: To determine loss of correction and factors
      affecting the loss of correction. STUDY DESIGN: Retrospective study. METHODS: A
      total of 49 corrected patients by Milwaukee brace participated minimum 2 years
      after treatment completion. The participants were categorized into two groups
      based on their roentgenograms: Group 1 (n = 36) had kyphotic curves of 45 degrees
      or less and Group 2 (n = 13) had kyphotic curves of more than 45 degrees .
      RESULTS: The mean loss of corrections for Group 1 and Group 2 were 3.80 degrees 
      (ranges = 0 degrees -13 degrees ) and 12.92 degrees  (ranges = 8 degrees -22
      degrees ), respectively. Group 1 showed no significant difference between the
      average hyperkyphosis of the patients for the part-time and full-time treatment
      duration (p = 0.02). By contrast, a significant difference was observed between
      the average hyperkyphosis of patients in Group 2 for the part-time and full-time
      treatment duration (p < 0.05). CONCLUSIONS: Patients with kyphosis of 60 degrees 
      or less who can save the correction in full-time orthotic treatment in part-time
      treatment may have the least loss of correction over time. CLINICAL RELEVANCE: As
      the orthotic treatment is a time-consuming method that needs the close
      collaboration of patient and treatment team, it is possible that clinicians
      predict the probable result of treatment and efficiency of orthotic treatment.
      Thus, a clinician can abandon orthotic treatment and refer the patient for an
      operation.

PMID- 23950553
TI  - Men's hostile sexism and biased perceptions of intimate partners: fostering
      dissatisfaction and negative behavior in close relationships.
AB  - Hostile sexism (HS) expresses attitudes that characterize women who challenge
      men's power as manipulative and subversive. Does endorsing HS negatively bias
      perceptions of women's behavior and, in turn, create animosity within intimate
      relationships? Committed heterosexual couples reported on their own behavior and
      perceptions of their partner's behavior five times across a year (Study 1) and
      daily for 3 weeks (Study 2). Men who more strongly endorsed HS perceived their
      partner's behavior as more negative than was justified by their partner's
      reports. Furthermore, more negative perceptions of the partner's behavior
      mediated the links between men's HS and feeling more manipulated by their
      partners, behaving more negatively toward their partners, and lower relationship
      quality. This indicates that men who endorse HS behave more negatively toward
      intimate partners and experience lower relationship satisfaction because their
      antagonistic attitudes toward women in general permeate the way they perceive
      those partners. 

PMID- 23950554
TI  - The remarkable robustness of the first-offer effect: across culture, power, and
      issues.
AB  - The first-offer effect demonstrates that negotiators achieve better outcomes when
      making the first offer than when receiving it. The evidence, however, primarily
      derives from studies of Westerners without systematic power differences
      negotiating over one issue-contexts that may amplify the first-offer effect.
      Thus, the present research explored the effect across cultures, among negotiators
      varying in power, and in negotiations involving single and multiple issues. The
      first two studies showed that the first-offer effect remains remarkably robust
      across cultures and multi-issue negotiations. The final two studies demonstrated
      that low-power negotiators benefit from making the first offer across single- and
      multi-issue negotiations. The second and fourth studies used multi-issue
      negotiations with distributive, integrative, and compatible issues, allowing us
      to show that first offers operate through the distributive, not the integrative
      or compatible issues. Overall, these results reveal that moving first can benefit
      negotiators across many organizational and personal situations. 

PMID- 23950555
TI  - Intergroup helping in response to separatism.
AB  - Despite its prevalence and widespread media coverage, separatism as a phenomenon
      is barely covered in psychological investigations, and the majority's response to
      separatism has been completely ignored. We present two studies in which we
      investigated the notion that separatist movements threaten the continuation of
      the national identity, as well as the nation's economic position. Moreover, we
      hypothesized and found that members of the majority group respond to continuation
      threat by supporting government measures to help the separatist group. Javanese
      students who were induced to believe that existing separatist movements in West
      Papua (Study 1, N = 322) or Aceh (Study 2, N = 180) were currently increasing
      their efforts to gain independence were more willing to support these groups than
      participants who believed these movements were dormant. Moreover, this effect was
      mediated by continuation threat but not economic threat. These results
      demonstrate the possibility of a peaceful response to separatism threat. 

PMID- 23950556
TI  - Maintaining hope at the 11th hour: authenticity buffers the effect of limited
      time perspective on hope.
AB  - Four studies tested the hypothesis that limited time perceptions are associated
      with lower levels of hope, and that this effect is buffered by high levels of
      authenticity. Study 1 (n = 256) utilized a cross-sectional design in which
      participants completed dispositional measures of time perspective, hope, and
      authenticity. Three subsequent studies tested our hypothesis experimentally. In a
      pilot study (n = 124), participants reported their perceived authenticity, future
      time perspective (FTP) was manipulated (limited vs. open-ended), and state hope
      was assessed. Study 2 (n = 156) introduced a new manipulation of FTP, and Study 3
      (n = 242) replicated Study 2 with the addition of a neutral control condition.
      Across all studies, individuals who perceived time as limited reported lower
      levels of hope relative to those who perceived time as open-ended (or those in a
      neutral control condition), but, importantly, this effect was attenuated for
      highly authentic individuals. 

PMID- 23950557
TI  - To belong is to matter: sense of belonging enhances meaning in life.
AB  - In four methodologically diverse studies (N = 644), we found correlational (Study
      1), longitudinal (Study 2), and experimental (Studies 3 and 4) evidence that a
      sense of belonging predicts how meaningful life is perceived to be. In Study 1 (n
      = 126), we found a strong positive correlation between sense of belonging and
      meaningfulness. In Study 2 (n = 248), we found that initial levels of sense of
      belonging predicted perceived meaningfulness of life, obtained 3 weeks later.
      Furthermore, initial sense of belonging predicted independent evaluations of
      participants essays on meaning in life. In Studies 3 (n = 105) and 4 (n = 165),
      we primed participants with belongingness, social support, or social value and
      found that those primed with belongingness (Study 3) or who increased in
      belongingness (Study 4) reported the highest levels of perceived meaning. In
      Study 4, belonging mediated the relationship between experimental condition and
      meaning. 

PMID- 23950558
TI  - A case of chronic wasting disease in a captive red deer (Cervus elaphus).
AB  - A 22-month-old, female red deer (Cervus elaphus) was submitted to the University
      of Minnesota Veterinary Diagnostic Laboratory for necropsy and chronic wasting
      disease (CWD) testing. The deer was found positive for the abnormal prion protein
      in the obex and the retropharyngeal lymph node by immunohistochemical staining.
      Microscopic lesions of spongiform encephalopathy and immunohistochemical staining
      patterns and intensity were similar to those in CWD-positive elk and
      experimentally infected red deer. 

PMID- 23950559
TI  - Response to letter regarding article, "CT perfusion in acute stroke: added value
      or waste of time?".

PMID- 23950560
TI  - CT perfusion in acute stroke: added value or waste of time?

PMID- 23950561
TI  - Evaluation of rural stroke services: does implementation of coordinators and
      pathways improve care in rural hospitals?
AB  - BACKGROUND AND PURPOSE: The quality of hospital care for stroke varies,
      particularly in rural areas. In 2007, funding to improve stroke care became
      available as part of the Rural Stroke Project (RSP) in New South Wales
      (Australia). The RSP included the employment of clinical coordinators to
      establish stroke units or pathways and protocols, and more clinical staff. We
      aimed to describe the effectiveness of RSP in improving stroke care and patient
      outcomes. METHODS: A historical control cohort design was used. Clinical practice
      and outcomes at 8 hospitals were compared using 2 medical record reviews of 100
      consecutive ischemic or intracerebral hemorrhage patients >=12 months before RSP
      and 3 to 6 months after RSP was implemented. Descriptive statistics and
      multivariable analyses of patient outcomes are presented. RESULTS:  SAMPLE: pre
      RSP n=750; mean age 74 (SD, 13) years; women 50% and post-RSP n=730; mean age 74
      (SD, 13) years; women 46%. Many improvements in stroke care were found after RSP:
      access to stroke units (pre 0%; post 58%, P<0.001); use of aspirin within 24
      hours of ischemic stroke (pre 59%; post 71%, P<0.001); use of care plans (pre
      15%; post 63%, P<0.001); and allied health assessments within 48 hours (pre 65%;
      post 82% P<0.001). After implementation of the RSP, patients directly admitted to
      an RSP hospital were 89% more likely to be discharged home (adjusted odds ratio,
      1.89; 95% confidence interval, 1.34-2.66). CONCLUSIONS: Investment in clinical
      coordinators who implemented organizational change, together with increased
      clinician resources, effectively improved stroke care in rural hospitals,
      resulting in more patients being discharged home.

PMID- 23950562
TI  - N-Linked glycosylation is essential for the yellow head virus replication cycle.
AB  - Yellow head virus (YHV) particles contain a nucleocapsid protein (p20) and two
      envelope glycoproteins (gp116 and gp64). The glycans attached to the two
      glycoproteins are N-linked and are complex and high mannose types, respectively.
      Here, we show that treatment with the N-linked glycosylation inhibitor
      tunicamycin in YHV-infected black tiger shrimp (Penaeus monodon) resulted in less
      severe yellow head disease and reduced mortality when compared with untreated
      control shrimp. Quantitative real-time reverse transcription PCR analysis also
      revealed lower YHV copy numbers in the haemolymph of treated than control shrimp.
      This was concurrent with less intense immuno-reactions in tissues of treated
      versus untreated shrimp using mAbs against all three YHV structural proteins. In
      addition, transmission electron microscopy of lymphoid organ tissue of the
      treated and untreated shrimp [eight collected at 36 h and eight at 48 h post
      infection (p.i.)] revealed only unenveloped nucleocapsids in all but one of the
      treated shrimp (collected at 48 h p.i.). By contrast, all the untreated shrimp
      showed a mixture of many unenveloped and enveloped virions. These results were
      supported by purification of YHV from the cell-free haemolymph of treated and
      untreated shrimp followed by YHV structural protein analysis by SDS-PAGE. It
      revealed three expected structural protein bands (116, 64 and 20 kDa) from the
      untreated shrimp but no structural protein bands from the tunicamycin-treated
      shrimp (confirmed by Western blot analysis). Overall, the results indicated that
      blocking glycosylation with tunicamycin inhibited the formation of mature YHV
      virions and their subsequent release into shrimp haemolymph, reducing the
      severity of disease.

PMID- 23950566
TI  - Synthetic routes to magnetic nanoparticles for MPI.
AB  - Magnetic particle imaging (MPI) is a new imaging technique for visualizing the
      three-dimensional distribution of superparamagnetic iron oxide nanoparticles with
      specific properties (MPI tracers). Initial results obtained with MPI using
      superparamagnetic iron oxide as blood pool markers suggest that the method has
      great potential for cardiovascular imaging. Conversely, no clinically approved
      MPI tracers currently exist that could be used to exploit this potential of MPI.
      This article describes thermal decomposition and coprecipitation, two relevant
      methods for synthesizing and optimizing superparamagnetic iron oxide
      nanoparticles for MPI. Furthermore it summarizes the recent literature on MPI
      tracers and explores what can be learned from structural studies with
      Resovist((r)) for novel synthesis approaches.

PMID- 23950563
TI  - H7N9 influenza viruses interact preferentially with alpha2,3-linked sialic acids
      and bind weakly to alpha2,6-linked sialic acids.
AB  - The recent human outbreak of H7N9 avian influenza A virus has caused worldwide
      concerns. Receptor binding specificity is critical for viral pathogenicity, and
      still not thoroughly studied for this emerging virus. Here, we evaluated the
      receptor specificity of the haemagglutinin (HA) of two human H7N9 isolates
      (A/Shanghai/1/13 and A/Anhui/1/13) through a solid-phase binding assay and a flow
      cytometry-based assay. In addition, we compared it with those from several HAs
      from human and avian influenza viruses. We observed that the HAs from the novel
      H7 isolates strongly interacted with alpha2,3-linked sialic acids. Importantly,
      they also showed low levels of binding to alpha2,6-linked sialic acids, but
      significantly higher than other avian H7s.

PMID- 23950567
TI  - Growth of very low birth weight infants after increased amino acid and protein
      administration.
AB  - AIM: To assess the impact of a high enteral protein nutrition strategy in human
      milk-fed very low birth weight (VLBW) infants (<1500 g) on growth during the
      first 5 weeks of life. DESIGN: Weight, length and head circumference of VLBW
      infants were recorded after introduction of a high protein strategy. RESULTS:
      Forty-three infants (median/interquartile range) of gestational age 27+6 weeks
      (26+0/29+6), birth weight 984 g (675/1130) were included. Parenteral nutrition
      was administered for 16 (14/18) days and the nutritional intakes achieved target
      values 4.3 g/kg/day protein (4.0/4.4); 128 kcal/kg/day energy (119/131). Human
      milk was fortified with 0.5-2.3 g/kg/day protein powder in addition to a
      fortifier. Near-intrauterine growth was observed: Weight gain from days 8-35:
      17.6 g/kg/day (14.9/20.5); head growth from day 1-35: 0.70 cm/week (0.50/0.80);
      length growth from day 1-35: 1.0 cm/week (0.8/1.2). The total protein intake was
      shown to have a significant impact on infant's weight gain up to the 35th day of
      life. CONCLUSION: High protein nutrition enables similar to fetal growth weight
      gain and head growth of VLBW infants during the first 5 weeks of life. These data
      support recently published ESPGHAN recommendations.

PMID- 23950568
TI  - Clinical and laboratory features of temporary brittle bone disease.
AB  - Temporary brittle bone disease has been described since 1990. It is a syndrome
      characterised by multiple unexplained fractures in early childhood. There is
      growing evidence that it has natural causes and does not represent inflicted
      trauma. We report the clinical and laboratory features of 104 patients
      investigated personally between 1985 and 2000. These patients had in aggregate
      976 fractures or fracture-like lesions. Our patients included disproportionate
      numbers of infants born preterm or as a result of multiple pregnancy. The
      fractures were mainly identified in the first 6 months of life and entirely
      within the first year of life. Most fractures were asymptomatic, particularly the
      many rib fractures and metaphyseal lesions. Few patients had evidence of bruising
      at presentation; none had clinical evidence of inflicted injury commensurate with
      the fractures found. In 22 patients the fractures were found in the course of
      investigation for unrelated symptoms. In several cases fractures took place while
      the children were in hospital. Unexplained bruising and sub-conjunctival
      haemorrhages also occurred in hospital, suggesting collagen defects. Hernias were
      recorded; in most these resolved spontaneously, again suggesting transient
      collagen defects. Among the unexplained symptoms of the patients was a history of
      vomiting, often projectile vomiting. Some patients had unusually blue or grey
      sclerae for the child's age. Many patients had abnormally large anterior
      fontanelles. Laboratory findings included anaemia, neutropenia and an
      exceptionally high serum alkaline phosphatase. Our findings reinforce the view
      that children with temporary brittle bone disease have a distinctive and
      identifiable syndrome which probably includes osteopathy of prematurity. These
      patients do not have osteogenesis imperfecta and are not the victims of non
      accidental injury. While the causes of this syndrome remain uncertain, its
      distinctive features should now be more readily recognised.

PMID- 23950570
TI  - Novel AQP2 mutation causing congenital nephrogenic diabetes insipidus: challenges
      in management during infancy.
AB  - Congenital nephrogenic diabetes insipidus (NDI) is a rare inherited disorder,
      mostly caused by AVPR2 mutations. Less than 10% of cases are due to mutations in
      the aquaporin-2 (AQP2) gene. Diagnosis and management of this condition remain
      challenging especially during infancy. Here, we report two unrelated patients, a
      6-month-old Thai boy and a 5-year-old Emirati girl, with a history of failure to
      thrive, chronic fever, polydipsia, and polyuria presented in early infancy. The
      results of water deprivation test were compatible with a diagnosis of NDI. The
      entire coding regions of the AVPR2 and AQP2 gene were amplified by polymerase
      chain reaction and sequenced. Patient 1 was homozygous for a novel missense AQP2
      mutation p.G96E, inherited from both parents. Patient 2 harbored a previously
      described homozygous p.T126M mutation in the AQP2 gene. Both patients were
      treated with a combination of thiazide diuretics and amiloride. Patient 1
      developed paradoxical hyponatremia and severe dehydration 2 weeks after medical
      treatment began. In conclusion, we report a novel mutation of the AQP2 gene and
      highlight an important role of genetic testing for definite diagnosis. Vigilant
      monitoring of the fluid status and electrolytes after beginning the therapy is
      mandatory in infants with NDI.

PMID- 23950569
TI  - Low-level hyperinsulinism with hypoglycemic spells in an infant with mosaic
      Turner syndrome and mild Kabuki-like phenotype: a case report and review of the
      literature.
AB  - BACKGROUND: Impaired glucose tolerance and type 2 diabetes are well-known
      features in patients with Turner syndrome. To the best of our knowledge, there is
      only one reported case of hyperinsulinemic hypoglycemia associated with a complex
      mosaic Turner syndrome available in the current literature. PATIENT: We report on
      the case of a 13-month-old girl with a complex mosaic Turner genotype and mild
      hyperinsulinemic hypoglycemia responsive to diazoxide therapy. RESULTS:
      Cytogenetic analyses showed two or possibly three cell lines. Sixty percent of
      the cell lines had a 45,X genotype and the rest had 46,XX with a marker ring
      chromosome. Diagnosis of a mosaic Turner syndrome and mild Kabuki-like phenotype
      was confirmed. CONCLUSIONS: Despite the rareness of this case, clinicians should
      be aware of the possibility of hyperinsulinemic hypoglycemia in patients with
      Turner syndrome to prevent further brain damage caused by hypoglycemic episodes
      and seizures. Although the mechanism leading to hyperinsulinism in this condition
      is still unknown, the present report discusses this rare presentation and gives
      an overview on the current literature regarding this case.

PMID- 23950571
TI  - Mutational analysis of KISS1 and KISS1R in idiopathic central precocious puberty.
AB  - AIM: The genetic background of idiopathic central precocious puberty (ICPP) is
      not well understood. The genetic activation of pubertal onset is thought to arise
      from the effect of multiple genes. Familial ICPP has been reported suggesting the
      existence of monogenic causes of ICPP. Kisspeptin and its receptor are found to
      be involved in gonadotropin-releasing hormone (GnRH) secretion and puberty onset.
      Mutations in their genes, KISS1 and KISSR, have been suggested to be causative
      for ICPP. METHODS: ICPP was defined by pubertal onset before 8 years of age in
      girls, and a pubertal luteinizing hormone (LH) response to GnRH testing. Twenty
      eight girls with ICPP were included in the study [age at diagnosis was 5.72+/
      2.59, with a mean bone age advancement of 1.4 years (-0.1 to 2.8). Height at
      onset of therapy in SD score was 0.90+/-1.48 for age]. Luteinizing hormone
      releasing hormone test was performed in all subjects, and all of them had a
      pubertal response (LH 20.35+/-32.37 mIU/mL; FSH 23.32+/-15.72 mIU/mL). The coding
      regions of KISS1 and KISS1R were sequenced. RESULTS: No rare variants were
      detected in KISS1 or KISS1R in the 28 subjects with ICPP. CONCLUSIONS: We
      confirmed that mutations in KISS1 and KISS1R are not a common cause for ICPP.

PMID- 23950572
TI  - Aging and speech perception: beyond hearing threshold and cognitive ability.
AB  - BACKGROUND: Older adults manifest difficulties in speech perception, especially
      when speech is accompanied by noise or when speech is rapid. Several explanations
      have been suggested to account for age-related changes in speech perception, such
      as changes in hearing sensitivity or a more general decline in cognitive
      functioning. The purpose of the present study was to directly examine the
      relative contribution of hearing sensitivity and perceptual and cognitive factors
      in the understanding of age-related differences in speech perception under
      difficult conditions. METHODS: Eighty-nine healthy participants with normal
      hearing thresholds, age 21-82 years, were tested for speech perception under four
      conditions: quiet, speech noise, white noise, and time-compressed speech at 60%
      compression rate. As all participants had age-normal hearing, absolute thresholds
      were tested for click trains, 1 kHz 15-ms duration pure tone, 1 kHz 50-ms
      duration pure tone, and 1.8 kHz 15-ms duration pure tone, which are relatively
      short and discriminative for hearing ability. Cognitive ability was examined
      using the Wechsler Adult Intelligence Scale (Third Edition) matrices and digit
      span. RESULTS: When words were presented against a quiet background or against
      white noise, speech perception was not significantly affected by aging, although
      in the latter case, increased thresholds predicted poorer speech perception.
      However, when words were presented against a background of speech noise or when
      speech was time-compressed at a 60% rate, age significantly predicted a decline
      in speech perception, even after controlling for hearing thresholds and cognitive
      functioning. CONCLUSIONS: Hearing threshold for short sounds is the major factor
      for predicting speech perception in background noise, across age, due to changes
      in hearing sensitivity or in temporal resolution. For the adult and aging
      population with preserved cognitive ability, cognitive functioning does not
      predict decline in speech perception.

PMID- 23950573
TI  - The effect of coadministration of alpha-tocopherol and ascorbic acid on arsenic
      trioxide-induced testicular toxicity in adult rats.
AB  - BACKGROUND: Arsenic, acting as an endocrine disruptor, causes reproductive
      malfunctions. Studies have been undertaken to find out whether the co
      supplementation of alpha-tocopherol and ascorbic acid (AT-AA) could reduce the
      arsenic-induced testicular toxicity caused by oxidative stress and resulting DNA
      damage. METHODS: Adult male Wistar rats (120+/-10 g) were given arsenic trioxide
      [3 mg/kg body weight (b.wt.) per day] for 30 consecutive days and the supplement
      group received alpha-tocopherol (400 mg/kg b.wt. per day) and ascorbic acid (200
      mg/kg b.wt. per day). Reproductive functions were evaluated with respect to the
      histoarchitecture, gametokinetic activity, androgenic potential, glutathione
      dependent antioxidant status and DNA damage of the testis. RESULTS: Arsenic
      treatment caused marked reduction in the relative weight of the testis (p<0.05)
      but showed no effect on body weight. The number of germ cells at stage VII of the
      spermatogenic cycle (p<0.01), the seminiferous tubular diameter (p<0.001) and
      Leydig cell nuclear area (p<0.01) were significantly reduced. Notable decrease in
      the activities of testicular Delta5, 3beta-HSD (p<0.05) and 17beta-HSD (p<0.01)
      with a concomitant fall in serum testosterone level (p<0.01) along with
      significant diminution in testicular glutathione S-transferase (p<0.05) activity
      and reduced glutathione level (p<0.01) were observed. Significant DNA damage
      (p<0.001) in spermatogenic cells was also noted. All these alterations including
      DNA strand breakage were seen to be protected with the coadministration of AT-AA.
      CONCLUSIONS: The data suggest that the protection of testicular toxicity in
      arsenic-exposed adult rats is possible with combined coadministration of AT-AA.

PMID- 23950575
TI  - Research forever - Klaus Jung.

PMID- 23950576
TI  - BDNF and VEGF in the pathogenesis of stress-induced affective diseases: an
      insight from experimental studies.
AB  - Stress is known to play an important role in etiology, development and
      progression of affective diseases. Especially, chronic stress, by initiating
      changes in the hypothalamic-pituitary-adrenal axis (HPA), neurotransmission and
      the immune system, acts as a trigger for affective diseases. It has been reported
      that the rise in the concentration of pro-inflammatory cytokines and persistent
      up-regulation of glucocorticoid expression in the brain and periphery increases
      the excitotoxic effect on CA3 pyramidal neurons in the hippocampus resulting in
      dendritic atrophy, apoptosis of neurons and possibly inhibition of neurogenesis
      in adult brain. Stress was observed to disrupt neuroplasticity in the brain, and
      growing evidence demonstrates its role in the pathomechanism of affective
      disorders. Experimental studies indicate that a well-known brain-derived
      neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) which
      have recently focused increasing attention of neuroscientists, promote cell
      survival, positively modulate neuroplasticity and hippocampal neurogenesis. In
      this paper, we review the alterations in BDNF and VEGF pathways induced by
      chronic and acute stress, and their relationships with HPA axis activity.
      Moreover, behavioral effects evoked in rodents by both above-mentioned factors
      and the effects consequent to their deficit are presented. Biochemical as well as
      behavioral findings suggest that BDNF and VEGF play an important role as
      components of cascade of changes in the pathomechanism of stress-induced
      affective diseases. Further studies on the mechanisms regulating their expression
      in stress conditions are needed to better understand the significance of trophic
      hypothesis of stress-induced affective diseases. 

PMID- 23950577
TI  - Magnesium in depression.
AB  - Magnesium is one of the most essential mineral in the human body, connected with
      brain biochemistry and the fluidity of neuronal membrane. A variety of
      neuromuscular and psychiatric symptoms, including different types of depression,
      was observed in magnesium deficiency. Plasma/serum magnesium levels do not seem
      to be the appropriate indicators of depressive disorders, since ambiguous
      outcomes, depending on the study, were obtained. The emergence of a new approach
      to magnesium compounds in medical practice has been seen. Apart from being
      administered as components of dietary supplements, they are also perceived as the
      effective agents in treatment of migraine, alcoholism, asthma, heart diseases,
      arrhythmias, renal calcium stones, premenstrual tension syndrome etc. Magnesium
      preparations have an essential place in homeopathy as a remedy for a range of
      mental health problems. Mechanisms of antidepressant action of magnesium are not
      fully understood yet. Most probably, magnesium influences several systems
      associated with development of depression. The first information on the
      beneficial effect of magnesium sulfate given hypodermically to patients with
      agitated depression was published almost 100 years ago. Numerous pre-clinical and
      clinical studies confirmed the initial observations as well as demonstrated the
      beneficial safety profile of magnesium supplementation. Thus, magnesium
      preparations seem to be a valuable addition to the pharmacological armamentarium
      for management of depression. 

PMID- 23950574
TI  - Rho-kinase: regulation, (dys)function, and inhibition.
AB  - In a variety of normal and pathological cell types, Rho-kinases I and II
      (ROCKI/II) play a pivotal role in the organization of the nonmuscle and smooth
      muscle cytoskeleton and adhesion plaques as well as in the regulation of
      transcription factors. Thus, ROCKI/II activity regulates cellular contraction,
      motility, morphology, polarity, cell division, and gene expression. Emerging
      evidence suggests that dysregulation of the Rho-ROCK pathways at different stages
      is linked to cardiovascular, metabolic, and neurodegenerative diseases as well as
      cancer. This review focuses on the current status of understanding the multiple
      functions of Rho-ROCK signaling pathways and various modes of regulation of Rho
      ROCK activity, thereby orchestrating a concerted functional response.

PMID- 23950578
TI  - Hippocampus, hippocampal sclerosis and epilepsy.
AB  - Hippocampal sclerosis (HS) is considered one of the major pathogenic factors of
      drug-resistant temporal lobe epilepsy. HS is characterized by selective loss of
      pyramidal neurons - especially of sectors CA1 and CA3 of the hippocampus -
      pathological proliferation of interneuron networks, and severe glia reaction.
      These changes occur in the course of long-term and complex epileptogenesis. The
      authors, on the basis of a review of the literature and own experience, present
      the pathomechanisms leading to hippocampal sclerosis and epileptogenesis,
      including various morphological and functional elements of this structure of the
      brain and pharmacological possibilities of preventing these processes. 

PMID- 23950579
TI  - Differential behavioral profile induced by the injection of dipotassium
      chlorazepate within brain areas that project to the nucleus accumbens septi.
AB  - BACKGROUND: The effect of the agonism on gamma-aminobutyric acid (GABA) receptors
      was studied within medial prefrontal cortex (mPFC), amygdala (AMY) and ventral
      hipocampus (VH) in the plus-maze test in male rats bilaterally cannulated. These
      structures send glutamatergic projections to the nucleus accumbens septi (NAS),
      in which interaction and integration between these afferent pathways has been
      described. In a previous study of our group, blockade of glutamatergic
      transmission within NAS induced an anxiolytic like effect. METHODS: Three rat
      groups received either saline or dipotassium chlorazepate (1 or 2 MUg/1 MUl
      solution) 15 min before testing. Time spent in the open arms (TSOA), time per
      entry (TPE), extreme arrivals (EA), open and closed arms entries (OAE, CAE) and
      relationship between open- and closed-arms quotient (OCAQ) were recorded.
      RESULTS: In the AMY injected group TSOA, OAE and EA were increased by the higher
      doses of dipotassium chlorazepate (p < 0.01). In the mPFC, TPE was decreased by
      both doses (p < 0.05). Injection within ventral hippocampus (VH) decreased TSOA,
      OAE and OCAQ with lower doses (p < 0.05). When the three studied saline groups
      were compared, TSOA, OAE, EA and OCAQ were enhanced in the VH group when compared
      to mPFC and AMY (p < 0.001). Insertion of inner canula (p < 0.001, p < 0.01, p <
      0.01) and saline injection showed an increasing significant difference (p < 0.001
      in all cases) with the action of guide cannula alone within VH in TSOA, OAE and
      EA. CONCLUSION: We conclude that the injection of dipotassium chlorazepate has a
      differential effect depending of the brain area, leading to facilitatory and
      inhibitory effects on anxiety processing.

PMID- 23950580
TI  - Zinc deficiency alters responsiveness to antidepressant drugs in mice.
AB  - BACKGROUND: There is some evidence coming from preclinical and clinical studies
      suggesting a relationship between dietary zinc intake and depressive symptoms.
      The aim of the study was to determine whether zinc deficiency alters the response
      to antidepressants with a different mechanism of action. We examine also whether
      these changes are related to activity of the hypothalamic-pituitary-adrenal HPA
      axis. METHODS: Male CD-1 mice were assigned to groups according to diet and
      antidepressant administration. To evaluate animal behavior, the immobility time
      in the forced swim test (FST) and locomotor activity were measured. To determine
      serum zinc levels the flame atomic absorption spectroscopy (FAAS) was used. The
      serum corticosterone was determined by radioimmunoassay (RIA). RESULTS:
      Antidepressants administered to zinc-deprived mice induced an altered response in
      the FST when compared to animals fed with an adequate diet. There were no changes
      in locomotor activity. Animals subjected to a zinc-deficient diet showed a
      significant reduction in serum zinc levels, which was normalized by
      antidepressant treatment. An increase in serum corticosterone concentrations in
      mice fed with a zinc-deficient diet and treated with antidepressants was
      observed, so it can be concluded that reduced levels of zinc contribute
      hyperactivation of the HPA axis. CONCLUSION: The results of this study suggest
      that a diet with a reduced zinc level alters antidepressant action, which is
      associated with a reduction in the serum zinc level and rise in the
      corticosterone level. The results of this study may indicate the involvement of
      zinc deficiency in the pathogenesis of depression.

PMID- 23950581
TI  - Repeated central administration of selegiline attenuated morphine physical
      dependence in rat.
AB  - BACKGROUND: Long-term exposure to opiates induces physical dependence; however,
      the neurobiological mechanisms of this phenomenon are not completely clear. The
      purpose of this study was to evaluate the effects of systemic and
      intracerebroventricular (icv) administration of selegiline (a selective inhibitor
      of monoamine oxidase B) on the morphine withdrawal syndrome in rats. METHODS: To
      this aim, adult male Sprague Dawley rats were selected randomly, and then growing
      doses of morphine were administered subcutaneously at an interval of 12 h for
      nine days with the intention of inducing dependency. Nine days after, only the
      morning dose of morphine was administered, followed by systemic or central
      injection of saline or selegiline. Later, naloxone was injected after 30 min and
      withdrawal signs recorded for a period of 60 min. RESULTS: Results showed failure
      of systemic administration of selegiline in changing the withdrawal symptoms;
      nevertheless, icv injection attenuated the withdrawal signs significantly.
      CONCLUSION: In conclusion we found that central administration of selegiline
      attenuated morphine withdrawal symptoms.

PMID- 23950582
TI  - Peripheral antinociception and anti-edematogenic effect of a sulfated
      polysaccharide from Acanthophora muscoides.
AB  - BACKGROUND: Sulfated polysaccharides from red marine algae have presented a
      variety of potentially therapeutic biological effects, however, their
      antinocicpetive and anti-inflammatory properties are not well understood.
      METHODS: Male Swiss mice were pretreated with a sulfated polysaccharidic fraction
      obtained from the marine alga Acanthophora muscoides (AmII) (1, 3 or 9 mg/kg, iv)
      30 min prior to either receiving an injection of 0.8% acetic acid or 1% formalin
      or prior to a thermal stimulus. AmII (1, 3 or 9 mg/kg, sc) was evaluated on
      carrageenan-, dextran- bradykinin-, histamine- and serotonin-induced rat paw
      edema models. AmII (500 MUg, sc) was also injected into the paw. Additionally,
      mice were treated with the total sulfated polysaccharides from A. muscoides (Am
      TSP) (20 mg/kg, ip) for 14 days. RESULTS: AmII reduced the number of acetic acid
      induced writhes and licking time in the second phase of the formalin test, but it
      did not alter the response latency in the hot plate test, suggesting that its
      antinociceptive action occurs through a peripheral mechanism. AmII did not reduce
      carrageenan-induced paw edema and MPO activity. However, it reduced dextran-,
      histamine- and serotonin-induced paw edemas, but not bradykinin-induced edema,
      suggesting that histamine is the major target of AmII anti-edematogenic activity.
      AmII injected into the paw did not evoke local edema. Furthermore, Am-TSP induced
      no consistent signs of systemic damage, as revealed by body mass, organs wet
      weight and by biochemical, hematological and histopathological analyses.
      CONCLUSION: AmII has important antinociceptive and anti-inflammatory properties
      and represents an important therapeutic agent warranting future studies.

PMID- 23950583
TI  - Negative influence of L-dopa on subjectively assessed sleep but not on nocturnal
      polysomnography in Parkinson's disease.
AB  - BACKGROUND: Sleep disorders are highly prevalent among patients with Parkinson's
      disease (PD). Chronic medication with L-dopa may be one of the factors that
      contributes to poor sleep quality. The aim of this study was to assess the
      effects of long term use of L-dopa on objective and subjective measures of sleep
      quality in PD patients. METHODS: Twenty-seven PD patients (mean age 62.5 +/- 8.6
      years, mean disease duration 7.3 +/- 5.9 years, 11 females) underwent nocturnal
      polysomnography. Their sleep was rated subjectively using the Parkinson's disease
      sleep scale (PDSS), and their disease severity was assessed using the unified
      Parkinson's disease severity scale (UPDRS) standard questionnaire. Doses of L
      dopa and other medications were correlated with parameters of sleep quality. The
      polysomnographic recordings were compared with those from 24 age- and gender
      matched normal controls. RESULTS: The patients showed decreased total sleep time
      (TST) and sleep efficiency (SE), prolonged sleep onset and REM sleep latency and
      wake after sleep onset (WASO). Parts I-III of the UPDRS scores correlated with
      TST, SE and WASO but not with PDSS scores. L-dopa dosage and part IV of the UPDRS
      correlated with PDSS scores but not with polysomnographic parameters.
      CONCLUSIONS: Higher doses of chronically administered L-dopa correlated with
      lower sleep quality according to the subjective measures but not according to the
      polysomnographic parameters, which were related to the severity of PD symptoms.
      The low sleep quality according to the subjective measurements may result from
      complications of therapy at high doses of L-dopa.

PMID- 23950584
TI  - Effects of diabetes and vascular occlusion on adenosine-induced relaxant response
      of rat common carotid artery.
AB  - BACKGROUND: The aim of this study was to investigate effect of adenosine on
      isolated rat common carotid artery (CA) submitted to occlusion in non-diabetic or
      diabetic animals, and to determine whether endothelium denudation or potassium
      conductance block affects adenosine action. METHODS: Experiments were conducted
      on Wistar rat CA with or without endothelium. Diabetes was induced by alloxan.
      Occlusion of CA was performed in randomly selected non-diabetic or diabetic
      animals anesthetized with urethane. Thus, experiments were performed in four
      groups of rats: non-operated (control) animals without or with diabetes and
      operated animals submitted to the occlusion of CA without or with diabetes.
      Concentration-response curves for adenosine were obtained in a cumulative fashion
      on precontracted arteries. RESULTS: Adenosine produced concentration-dependent
      and endothelium-independent relaxation of CA with comparable maximal effects in
      all groups. Analysis of pEC50 values showed that responsiveness of CA decreased
      in following order: [diabetes (-) / occlusion (-)] = [diabetes (-) / occlusion
      (+)] > [diabetes (+) / occlusion (-)] > [diabetes (+) / occlusion (+)]. In the
      presence of high K(+) maximal relaxant response of CA from non-operated rats
      without diabetes was reduced. The recorded inhibition was even stronger in
      animals subjected to CA occlusion. Conversely, in non-operated diabetic animals
      obtained reduction of adenosine effect was less pronounced in regard to non
      diabetic rats. CONCLUSIONS: Adenosine produced equi-effective endothelium
      independent relaxation of CA in all groups. Pharmacological potency of adenosine
      was reduced in diabetic animals solely, but even more in diabetic rats submitted
      to CA occlusion. The enhanced potassium transmembrane flow has certain protective
      role on adenosine-induced action in occluded CA from non-diabetic rats.
      Conversely, diabetes solely inhibited adenosine-evoked cascade connected to
      increased potassium conductance.

PMID- 23950585
TI  - Effect of natalizumab on oxidative damage biomarkers in relapsing-remitting
      multiple sclerosis.
AB  - BACKGROUND: Natalizumab is a monoclonal antibody used to treat multiple
      sclerosis. This study sought to determine whether the protective action of
      natalizumab involved a reduction in oxidative damage. METHODS: Twenty-two
      multiple sclerosis patients fulfilling the revised McDonald criteria were
      assigned to treatment with 300 mg natalizumab intravenously once monthly
      (infusion every 4 weeks) in accordance with Spanish guidelines. Carbonylated
      proteins, 8-hydroxy-2'-deoxyguanosine, total glutathione, reduced glutathione,
      superoxide dismutase, glutathione peroxidase, and myeloperoxidase levels were
      measured at baseline and after 14 months' treatment, and the antioxidant gap was
      calculated. RESULTS: Natalizumab prompted a drop in oxidative-damage biomarker
      levels, together with a reduction both in myeloperoxidase levels and in the
      myeloperoxidase/neutrophil granulocyte ratio. Interestingly, natalizumab induced
      nuclear translocation of Nrf2 and a fall in serum vascular cell adhesion molecule
      1 levels. CONCLUSION: These findings suggest that natalizumab has a beneficial
      effect on oxidative damage found in MS patients.

PMID- 23950586
TI  - Melatonin-induced augmentation of collagen deposition in cultures of fibroblasts
      and myofibroblasts is blocked by luzindole--a melatonin membrane receptors
      inhibitor.
AB  - BACKGROUND: Melatonin has been proven to have a regulatory influence on collagen
      accumulation in different types of wound. It was found to inhibit collagen
      accumulation in the superficial wound model but increase it in the myocardial
      infarction scar. The aim of the study is to determine the mechanism of melatonin
      action in the two wound types in rats. METHODS: Cells were isolated from both the
      superficial wound (subcutaneously inserted polypropylene net) and myocardial
      infarction scar (induced by ligation of the left coronary artery) and were
      identified by electron microscopy. RESULTS: Long-shaped cells forming whirl-like
      structures in culture (mainly identified as fibroblasts) were isolated from the
      superficial wound model, while myofibroblasts growing in a formless manner were
      acquired from the infarcted heart scar. Melatonin (10(-7) M) increased collagen
      accumulation in both fibroblast and myofibroblast cultures. Luzindole (10(-6) M),
      the blocker of both MT1 and MT2 melatonin membrane receptors, inhibited the
      effect of melatonin on the two types of cells. CONCLUSION: Regardless of various
      healing potentials demonstrated by the tested cells (different cell composition,
      growth and organization), their response to melatonin was similar. Moreover, in
      the two investigated cultures, augmentation of the collagen content by melatonin
      was reversed by luzindole, which indicates the possibility of melatonin membrane
      receptor involvement in that process. The present results suggest that the
      increased melatonin-stimulated deposition of collagen observed in the infarcted
      heart of rats could be dependent on activation of the melatonin membrane
      receptors on scar myofibroblasts.

PMID- 23950587
TI  - Study of the interaction of glutamatergic and nitrergic signalling in conditions
      of the experimental airways hyperreactivity.
AB  - BACKGROUND: Glutamatergic and nitrergic system participate in the control of
      respiratory system functions. It is only little information regarding a possible
      interaction of both systems in the airways hyperractivity. We investigated the
      effect of agents modulating the activity of these systems on the experimental
      ovalbumin-induced airways hyperreactivity as well as on the changes of exhaled
      nitric oxide (eNO) levels. METHODS: We used the agonists of NMDA receptors - N
      methyl-D-aspartic acid (NMDA) and monosodium glutamate (MSG), selective
      competitive antagonist (DL-2-amino-5-phosphonovaleric acid - AP-5) and selective
      non-competitive antagonist (dizocilpine - MK-801) of these receptors. We used
      also non-specific inhibitor of NO synthases N(omega)-nitro-L-arginine methyl
      ester (L-NAME). The airways responsiveness to histamine or acetylcholine was
      evaluated under in vitro conditions. RESULTS: NMDA administration caused the
      increase of tracheal smooth muscle response in ovalbumin-induced hyperreactivity
      to acetylcholine. The effect of MSG was less pronounced. MK-801 as well as AP-5
      provoked the decrease of reactivity mainly to acetylcholine in tracheal smooth
      muscle. We recorded the changes in eNO levels. The activation of NMDA receptor
      with NMDA or MSG increased eNO levels. The inhibition of NO synthase with L-NAME
      caused the fall of eNO levels. MK-801 shows (within the group) the more
      expressive effect in the eNO levels during sensitization than AP-5 group.
      CONCLUSION: The results confirm the possibility of NMDA receptors participation
      in the experimental airways hyperreactivity.

PMID- 23950588
TI  - Modulatory effects of sesamol in dinitrochlorobenzene-induced inflammatory bowel
      disorder in albino rats.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory condition
      of gastrointestinal tract of immune, genetic and environmental origin. In the
      present study, we examined the effect of sesamol (SES), the main anti-oxidative
      constituent of Sesamum indicum (sesame seed) Linn. in the dinitrochlorobenzene
      (DNCB)-induced model for IBD in rats. METHODS: The groups were divided into
      normal control, DNCB control, SES and sulfasalazine (SS). On day 24, the rats
      were killed, colon removed and the macroscopic, biochemical and histopathological
      evaluations were performed. RESULTS: The levels of MPO, TBARS and nitrite
      increased significantly (p < 0.05) in the DNCB group, whereas reduced
      significantly in the SES, SS treated groups. Serum nitrite levels were found to
      be insignificant between the different groups. IL-6 and TNF-alpha levels were
      significantly high in the DNCB group. CONCLUSIONS: We conclude the mucosal
      protective effect of SES on colon due to its potent antioxidant actions. Further
      investigation is required in a chronic model of different rodent strain for its
      role involved in the cytokine pathway.

PMID- 23950589
TI  - Long-term inhibition of intestinal lipase by orlistat improves release of gut
      hormones increasing satiety in obese women.
AB  - BACKGROUND: Reduced postprandial secretion of peptide YY (PYY), glucagon-like
      peptide-1 (GLP-1), cholecystokinin, and increased hunger was reported after a
      single dose of orlistat, an inhibitor of intestinal lipase. As yet, the influence
      of long-term therapy with orlistat on PYYand GLP-1 release has not been studied.
      Our study was aimed at assessing the influence of 8-week therapy with orlistat as
      a component of a weight loss program on pre-prandial circulating PYY and GLP-1
      levels. METHODS: Forty obese women, without concomitant diseases, were randomly
      allocated to groups receiving orlistat or placebo during an 8-week weight
      management program. Body mass, body composition and plasma levels of PYY, GLP-1
      and insulin (for QUICKI calculation) were determined prior to and at the end of
      therapy. RESULTS: Women treated with orlistat obtained significantly greater body
      and fat mass loss than those receiving placebo (9.0 +/- 3.1 vs. 5.9 +/- 3.2% and
      21.9 +/- 10.9 vs. 7.4 +/- 15.6%, respectively). Only in those treated with
      orlistat a slight, but significant increase of the QUICKI was found (8.0 +/- 16.5
      vs. -0.1 +/- 12.7 %, respectively). Weight loss was followed by a significant
      increase of plasma levels of PYY and GLP-1 in group treated with orlistat, and
      was about 2-times greater than receiving placebo. The increase was independent of
      body mass changes. CONCLUSION: The long-term inhibition of intestinal lipase by
      orlistat increases the pre-prandial levels of GLP-1 and PYY, independent of body
      mass changes. Therefore, it seems that long-term treatment with orlistat may
      exert hunger suppressing and insulin sensitizing incretin effect beyond weight
      reduction.

PMID- 23950590
TI  - Inhibitory effect of antidepressants on B16F10 melanoma tumor growth.
AB  - BACKGROUND: Antidepressant drugs, like fluoxetine, a selective serotonin reuptake
      inhibitor, desipramine, a nonselective noradrenaline reuptake inhibitor, and
      mirtazapine, an antagonist of noradrenaline alpha2 auto- and heteroreceptors, are
      widely used for the treatment of depressive symptoms in cancer patients. Since
      these antidepressants have different activities targeting the immune system, they
      might also modulate tumor growth in cancer patients. METHODS: In the present
      study, we investigated the effects of administration of antidepressant drugs:
      fluoxetine, desipramine and mirtazapine on B16F10 melanoma tumor growth. These
      drugs were administered intraperitoneally (ip) for 17 days after subcutaneous
      injection of B16F10 melanoma cells to male C57BL/6J mice. RESULTS: Fluoxetine
      significantly inhibited melanoma solid tumor growth and desipramine tended to
      decrease this parameter whereas mirtazapine had no effect. CONCLUSION: The
      inhibitory effect of fluoxetine on melanoma growth was associated with an
      increased mitogen-induced T cell proliferation which may at least partly
      participate in the mechanism of the antitumor effect of this antidepressant. It
      appears that the inhibitory effect of fluoxetine on tumor growth is not related
      with changes in cytokine levels except for IL-10.

PMID- 23950591
TI  - Cucurmosin induces the apoptosis of human pancreatic cancer CFPAC-1 cells by
      inactivating the PDGFR-beta signalling pathway.
AB  - BACKGROUND: Pancreatic cancer treatment is limited and effective drugs are
      needed. We investigated cucurmosin (CUS)-induced apoptosis in cystic fibrosis
      pancreatic adenocarcinoma cells (CFPAC-1) and a possible mechanism of action to
      evaluate the clinical application potential of this new Type I ribosome
      inactivating protein. METHODS: We analyzed the growth inhibition and apoptosis of
      CFPAC-1 cells via methylthiazol tetrazolium assay and fluorescence-activated cell
      sorting. Western blot was used to analyze the protein levels of caspase 3, bcl-2,
      caspase 9, platelet-derived growth factor receptor (PDGFR)-beta, PI3K, Akt, p
      Akt, the mammalian target of rapamycin (mTOR), p-mTOR, P70S6K-alpha, p-P70S6K
      alpha, 4E-BP1, p-4E-BP1 and p-Bad after CUS intervention. The mRNA expression of
      PDGFR-beta was analyzed using reverse transcription polymerase chain reaction.
      RESULTS: CUS inhibited the proliferation of pancreatic cancer cells. The
      induction of apoptosis depended on the CUS dose and incubation time. The drug
      inhibited all of the examined proteins in the PI3K/Akt/mTOR signalling pathway
      and induced the active fragments of caspase 3 and caspase 9. CUS downregulated
      PDGFR-beta expression but no significant change was observed at the mRNA level.
      CONCLUSION: CUS strongly inhibits the growth of CFPAC-1 by inducing cell
      apoptosis. CUS downregulated the expression of PDGFR-beta at the protein level
      and induced the apoptosis of CFPAC-1 through the PI3K/Akt/mTOR signalling
      pathway.

PMID- 23950592
TI  - Cytotoxic effect of lomefloxacin in culture of human epidermal melanocytes.
AB  - BACKGROUND: Lomefloxacin is a potent bactericidal antibiotic. The use of this
      drug in treatment of various infections is accompanied by serious adverse effects
      on pigmented tissues. The exact mechanisms of lomefloxacin side effects have not
      been well established yet. The aim of this study was to characterize the
      interaction between lomefloxacin and melanin, and to examine how this interaction
      affects the cell viability and melanization in melanocytes. METHODS: Normal human
      epidermal melanocytes and the model DOPA-melanin were used. The binding
      parameters of lomefloxacin-melanin complexes as well as the antibiotic effect on
      cell viability and melanization in pigmented cells were investigated using a
      spectrophotometric method. RESULTS: Our results indicate that lomefloxacin forms
      stable complexes with melanin. The analysis of drug binding to melanin has shown
      that at least two classes of independent binding sites are involved in formation
      of these complexes. The WST-1 assay was used to detect the antibiotic cytotoxic
      effect. The value of ED50 for lomefloxacin was about 0.75 mmol/l. It has been
      shown that lomefloxacin causes inhibition of tyrosinase activity, and reduces
      melanin content in human skin melanocytes in a dose-dependent manner. CONCLUSION:
      The ability of the analyzed fluoroquinolone to form complexes with melanin, and
      the demonstrated inhibitory effect on a melanization process in melanocytes in
      vitro may explain a potential role of melanin biopolymer in the mechanisms of
      undesirable side effects of lomefloxacin in vivo resulting from its accumulation
      in pigmented tissues.

PMID- 23950593
TI  - Bisdemethoxycurcumin suppresses MCF-7 cells proliferation by inducing ROS
      accumulation and modulating senescence-related pathways.
AB  - BACKGROUND: Bisdemethoxycurcumin (BDMC) is a natural derivative of curcumin
      present in the phenolic components extracted from the dried rhizome of Curcuma
      longa L. BDMC demonstrated potential chemotherapeutic activities but the
      underlying mechanisms have not been fully clarified. In the present study, the
      role of reactive oxidative species (ROS) in the anti-cancer effects of BDMC was
      investigated. METHODS: MCF-7 cells were exposed to BDMC, and then the cell
      proliferation, colony formation ability and cell cycle profile were analyzed.
      Cellular ROS level was determined by flow cytometry and fluorescent microscope
      observation using specific fluorescent probes. Mitochondrial membrane potential
      (psim) was assessed using JC-1. In addition, effects of BDMC on senescence
      related molecules were analyzed by western blot assay. RESULTS: BDMC
      significantly inhibited MCF-7 breast cancer cell proliferation, while a rapid
      rise of the intracellular ROS level accompanied with a reduction of Dym were
      observed. In addition, BDMC activated the pro-apoptotic protein p53 and its
      downstream effector p21 as well as the cell cycle regulatory proteins p16 and its
      downstream effector retinoblastoma protein (Rb). All of these BDMC-induced
      effects were counteracted with the pre-incubation of the antioxidant N
      acetylcysteine (NAC). CONCLUSIONS: These results suggested that BDMC-induced ROS
      accumulation may contribute to its inhibitory effect on MCF-7 cell viability
      through regulation of p53/p21 and p16/Rb pathways.

PMID- 23950595
TI  - Evaluation of the anti-proliferative activity of three new pyrazole compounds in
      sensitive and resistant tumor cell lines.
AB  - BACKGROUND: In previous papers we demonstrated that the activity of short
      heteroretinoids as anti-proliferative and pro-apoptotic compounds was deeply
      linked to their heterocyclic moiety and that ionone-derived 1,5-pyrazoles had the
      highest anti-proliferative activity in our preliminary experiments. We then
      demonstrated the high and pharmacologically significant anti-proliferative and
      apoptotic activities of the pyrazole compounds 2-(1-(4-chlorophenyl)-1H-pyrazol-5
      yl)-5-methoxyphenol (EN12-4), 5-methoxy-2-(1-(pyridin-2-yl)-1H-pyrazol-5
      yl)phenol (EN12-2A) and 2-(5-(4-methoxyphenyl)-1H-pyrazol-1-yl)pyridine (EN7-2)
      establishing, especially for EN12-2A, a possible mechanism of action involving
      the cell microtubular system. METHODS: Here, the anti-proliferative activity of
      these pyrazole compounds was analyzed in vitro by the MTT assay in six drug
      resistant cell lines, five of which were selected after exposure to increasing
      concentrations of cisplatin (L1210/DDP), doxorubicin (A2780/DX3), 5-fluorouracil
      (HCT-8/5FU), taxol (A549/T24) and etoposide (MCF-7/VP), and one was obtained by
      transfection of the ABCG2 membrane transporter (HEK-293/R2). RESULTS: Our data
      show that these compounds have a similar anti-proliferative activity in nearly
      all resistant and sensitive cell lines, demonstrating their ability to overcome
      the most common mechanisms of drug resistance with two exceptions regarding the
      MCF-7/VP cell line over-expressing the ABCC1 (MRP1) transporter, and the MDR1
      over-expressing A2780/DX3 cells, with a calculated RI = 3.2 for EN12-2A, relative
      to their sensitive cellular counterpart. On the other hand, the taxol-resistant
      A549/T24 cell line showed a significantly increased sensitivity to our compounds.
      CONCLUSIONS: Our data suggest that our pyrazole compounds are able to overcome in
      vitro the most common drug-resistance mechanisms demonstrating a significant anti
      proliferative activity and confirming a mechanism of action involving the
      depolymerization of microtubules.

PMID- 23950594
TI  - Involvement of spinal PKA/CREB signaling pathway in the development of bone
      cancer pain.
AB  - BACKGROUND: It has been shown that spinal PKA/CREB signaling pathway is involved
      in neuropathic and inflammatory pain, but its effects on bone cancer pain have
      not previously been investigated. The aim of this study was to examine the
      potential role of the spinal PKA/CREB signaling pathway in the development of
      bone cancer pain. METHODS: A bone cancer pain model was made by inoculation of
      Walker 256 cells into the intramedullary space of rat tibia. Western blot
      analysis examined the expression of PKAca (PKA catalytic subunit) and phospho
      CREB (p-CREB) protein levels. The authors further investigated effects of
      intrathecal treatment with H-89 (a PKA inhibitor, 8 nmol) or forskolin (a PKA
      agonist, 10 nmol) on nociceptive behavior and the expression of PKAca and p-CREB.
      RESULTS: On days 6, 9, and 15 after inoculation, the expression of PKAca and p
      CREB protein levels were higher in the bone cancer pain rats compared to the sham
      rats. On day 9, intrathecal administration of H-89 significantly attenuated bone
      cancer-induced mechanical allodynia as well as upregulation of PKAca and p-CREB
      protein levels. These effects were completely abolished by intrathecal
      pretreatment with the PKA agonist forskolin. CONCLUSION: The results suggest that
      the spinal PKA/CREB signaling pathway may participate in the development of bone
      cancer pain. The findings of this study may provide an evidence for developing
      novel analgesics to block bone cancer pain.

PMID- 23950596
TI  - Effects of olanzapine and paroxetine on phospholipase D activity in the rat
      brain.
AB  - BACKGROUND: Phospholipase D (PLD) plays a key role in a second messenger system
      producing phosphatidic acid, mediating, among others, serotonin 5-HT2 receptor
      activity. The aim of the study was to evaluate a possible effect of atypical
      antipsychotic drug, olanzapine (OLZ), and selective serotonin reuptake inhibitor
      (SSRI) antidepressant, paroxetine (PX), on oleate-activated PLD activity in
      plasma membranes isolated from rat brain cortex. METHODS: PLD activity was
      determined using a fluorometric assay. Ritanserin was used to determine the 5-HT
      receptor mode of action. RESULTS: A single dose of 10 mmol/kg OLZ produced no
      change in rat brain cortex PLD activity, 20 mmol/kg OLZ caused a nonsignificant
      decrease, and long-term (21 days) administration of OLZ resulted in a 41.9%
      decrease in PLD activity. Single doses of PX significantly decreased PLD
      activity: 10 mmol/kg - by 28.6%; 20 mmol/kg - by 31.5%, and long-term (21 days)
      administration of PX - by 39.5%. CONCLUSION: The study indicates that the 5-HT2
      receptor-mediated inhibition of oleate-activated PLD may be a common part of the
      mechanisms of action of OLZ and PX.

PMID- 23950597
TI  - Study of the protective effect of calcium channel blockers against neuronal
      damage induced by glutamate in cultured hippocampal neurons.
AB  - BACKGROUND: The aim of this study was to examine the putative protective effect
      of calcium channel blockers on hippocampal neurons in the experimental model of
      excitotoxic damage. METHODS: Seven-day old primary dissociated cultures of rat
      hippocampal neural cells containing one of the following calcium channel
      blockers: cinnarizine, flunarizine or nimodipine were exposed to glutamate
      induced injury. Quantitative assessments of neuronal injury were accomplished by
      measuring lactate dehydrogenase (LDH) activity in the media 24 h after exposure
      to glutamate and by counting and establishing the apoptotic and necrotic cells in
      flow cytometry with Annexin V-FITC/PI staining. RESULTS: In our experiment,
      glutamate induced a 339% elevation of apoptotic cells and a 289% increase of
      necrotic cells in hippocampal neurons as compared to control cultures without
      drugs. In cultures containing flunarizine, glutamate-induced cell apoptosis was
      suppressed by 62% while necrosis showed no significant alternation. Cinnarizine
      exerted no anti-apoptotic effects on glutamate-injured cultured hippocampal
      neurons, while nimodipine intensified the apoptotic pathway of cell death and
      promoted an increase in the number of apoptotic neurons by 26%. When cinnarizine
      or nimodipine were used, the percentage of necrotic cells was significantly lower
      when compared with glutamate-injured cultures and it amounted to 44% and 24% for
      cinnarizine and nimodipine, respectively. CONCLUSIONS: The obtained results
      suggest the beneficial anti-apoptotic potential of flunarizine and the anti
      necrotic potential of cinnarizine against glutamate-induced death of cultured
      hippocampal neurons. Nimodipine can protect neurons against necrosis, but has an
      intensified adverse pro-apoptotic effect on cultured neurons in the experimental
      model of excitotoxic injury.

PMID- 23950598
TI  - Metformin raises hydrogen sulfide tissue concentrations in various mouse organs.
AB  - BACKGROUND: The epidemic of diabetes mellitus type 2 forces to intensive work on
      the disease medication. Metformin, the most widely prescribed insulin sensitizer,
      exerts pleiotropic actions on different tissues by not fully recognized
      mechanisms. Hydrogen sulfide (H2S) is involved in physiology and pathophysiology
      of various systems in mammals and is perceived as a potential agent in the
      treatment of different disorders. The interaction between biguanides and H2S is
      unknown. The aim of the study is to assess the influence of metformin on the H2S
      tissue concentrations in different mouse organs. METHODS: Adult SJL female mice
      were administered intraperitoneally 100 mg/kg b.w. per day of metformin (group
      D1, n = 6) or 200 mg/kg b.w. per day of metformin (group D2, n = 7). The control
      group (n = 6) received physiological saline. The measurements of the free and
      acid-labile H2S tissue concentrations were performed with Siegel
      spectrophotometric modified method. RESULTS: There was a significant progressive
      increase in the H2S concentration along with the rising metformin doses as
      compared to the control group in the brain (D1 by 103.6%, D2 by 113.5%), in the
      heart (D1 by 11.7%, D2 by 27.5%) and in the kidney (D1 by 7.1%, D2 by 9.6%). In
      the liver, massive H2S accumulation was observed in the group D1 (increase by
      420.4%), while in the D2 group only slight H2S level enhancement was noted (by
      12.5%). CONCLUSION: Our experiment has shown that metformin administration is
      followed by H2S tissue concentrations increase in mouse brain, heart, kidney and
      liver.

PMID- 23950599
TI  - Effect of the nutritional supplement ALAnerv(r) on the serum PON1 activity in
      post-acute stroke patients.
AB  - BACKGROUND: Paraoxonase-1 (PON1) is one of the HDL-associated proteins which
      contributes to the antioxidant properties of these lipoproteins. The aim of this
      pilot study was to evaluate the effect of the nutritional supplement ALAnerv(r)
      on serum PON1 activity in post-acute stroke patients undergoing rehabilitation.
      METHODS: We enrolled 28 post-acute stroke patients and randomly divided them into
      (-) ALA or (+) ALA study groups. All the patients underwent the same
      rehabilitation program and received comparable standard medications. Moreover,
      (+) ALA patients received ALAnerv(r) for two weeks (2 pills/day). The serum PON1
      activity was assessed on blood samples taken at the admission and at the
      discharge moments, respectively. We used paraoxon (paraoxonase activity, PONA),
      phenyl acetate (arylesterase activity, ARYLA) and dihydrocoumarin (lactonase
      activity, LACTA) as substrates, the latter activity being regarded as
      physiologically relevant. A control group of 14 apparently healthy subjects was
      also created. RESULTS: In the (+) ALA group, LACTA significantly increased during
      the study period (17.6 +/- 3.2 vs. 27.6 +/- 3.5, p = 0.002). Moreover, the
      percentage of LACTA variation between (-) ALA and (+) ALA groups during the study
      was also statistically different (-11.7 +/- 6.9% vs. +95.1 +/- 29.7%, p <
      0.0001). CONCLUSIONS: These preliminary results suggest that ALA nerv(r) could
      contribute to the improvement of the physiologically relevant LACTA of PON1 in
      post-acute stroke patients, enabling this enzyme to contribute to the redox
      correction. Also, this study raises the question about the effect of a longer
      treatment period over the other enzymatic activities of serum PON1.

PMID- 23950600
TI  - Expression of multiple Transient Receptor Potential channel genes in murine 3T3
      L1 cell lines and adipose tissue.
AB  - BACKGROUND: Calcium and its signaling have a role in adipogenesis. Transient
      Receptor Potential (TRP) channels are non-selective cation channels with a high
      permeability to calcium. METHODS: In the present study the expression of multiple
      TRP channels on mouse 3T3-L1 preadipocyte and adipocyte cells, white (WAT) and
      brown (BAT) adipose tissues was investigated using real time PCR (RT-PCR).
      RESULTS: TRPV1, TRPV3, TRPM8, TRPC4, TRPC6 were differentially expressed in
      preadipocytes and adipocytes suggesting their significance in adipogenesis. Genes
      for multiple TRP channels were also expressed in murine WAT and BAT, out of which
      TRPV4, TRPV6 and TRPC6 showed differential expression. CONCLUSION: Present study
      demonstrates the expression of TRP channels in mouse cell lines and adipose
      tissues.

PMID- 23950601
TI  - Lymphocyte-suppressing action of simvastatin in patients with isolated
      hypertriglyceridemia.
AB  - BACKGROUND: No previous study examined whether statins affect lymphocyte cytokine
      release in patients with isolated hypertriglyceridemia. METHODS: The study
      included 46 patients with elevated triglyceride levels and peripheral artery
      stenosis, randomly assigned to receive simvastatin or placebo. Plasma lipids,
      glucose homeostasis markers, plasma C-reactive protein and lymphocyte cytokine
      release were measured at baseline and at the end of the treatment. RESULTS:
      Ninety-day simvastatin treatment reduced lymphocyte release of TNF-alpha,
      interleukin-2 and interferon-gamma, which was accompanied by a decrease in plasma
      C-reactive protein. CONCLUSION: The obtained results suggest that statins produce
      lymphocyte-suppressing and systemic anti-inflammatory effects in patients with
      isolated hypertriglyceridemia.

PMID- 23950602
TI  - Effect of anhydrosophoradiol-3-acetate of Calotropis gigantea (Linn.) flower as
      antitumoric agent against Ehrlich's ascites carcinoma in mice.
AB  - BACKGROUND: Over 60% of currently used anti-cancer agents are derived in one-way
      or another from natural sources, including plants, marine organisms and
      microorganisms. Calotropis gigantea (Linn.) (Family: Asclepiadaceae) is a
      perennial shrub and it is used as a traditional folk medicine for the treatment
      of various health complications. But there is no report on isolation of
      anticancerous chemicals from the flower of Calotropis gigantea. The objective of
      the present study is to explore the antitumor effect of anhydrosophoradiol-3
      acetate (A3A), isolated from the flower of Calotropis gigantea (Linn.) against
      Ehrlich's ascites carcinoma (EAC) in Swiss albino mice. METHODS: Antitumoric
      effect of A3A was assessed by evaluating viable tumor cell count, survival time,
      body weight gain due to tumor burden, hematological and biochemical (glucose,
      cholesterol, triglyceride, blood urea, SALP, SGPT and SGOT) parameters of EAC
      bearing host at doses of 10 and 20 mg/kg body weight. RESULTS: Treatment with A3A
      decreased the viable tumor cells and body weight gain thereby increasing the life
      span of EAC bearing mice. A3A also brought back the altered hematological (Hb,
      total RBC and total WBC) and biochemical parameters more or less to normal level.
      CONCLUSION: Results of this study conclude that in vivo the A3A was effective in
      inhibiting the growth of EAC with improving in cancer induced complications.

PMID- 23950603
TI  - The conundrum of clinical practice guidelines.

PMID- 23950604
TI  - Assessment of clinical pharmacy interventions in the intensive care unit.
AB  - BACKGROUND: Clinical pharmacy services have been shown to reduce adverse drug
      events and health care costs. However, few studies have assessed their effect on
      patient outcomes in the intensive care unit (ICU). OBJECTIVE: To describe
      characteristics of ICU patients with documented pharmacist interventions and to
      evaluate the relationships between patients' complexity level and pharmacists'
      interventions and between pharmacists' interventions and mortality rate. METHODS:
      Inpatient records of admissions between January 1, 2004, and March 31, 2007, were
      analyzed to identify the presence of clinical pharmacy notes (CPNs). The
      characteristics of patients with and without CPNs were compared using descriptive
      statistics. For primary analysis of the association between patient complexity
      level and presence of CPNs, logistic regression modelling was performed to adjust
      for potential confounding. Logistic regression was also used to explore the
      possible association between CPNs and mortality. Finally, mortality analysis was
      carried out for patients with and without CPNs, with matching by complexity
      level. RESULTS: The main study cohort comprised 1561 patients: 333 (21.3%) with
      CPNs and 1228 (78.7%) with no CPNs. A greater proportion of those with a CPN had
      the highest complexity level: 295 (88.6%) of those with CPNs versus 660 (53.7%)
      of those with no CPNs. After adjustment for age and sex, the odds ratio for
      having a CPN among patients with complexity level 4 (relative to patients with
      lower complexity levels) was 8.20 (95% confidence interval 5.44-12.38). Mortality
      rates were not significantly different between the 2 groups: 26.7% (89/333) among
      patients with CPNs and 27.9% (343/1228) among those without CPNs (p = 0.66).
      After adjustment for age, sex, complexity level, and length of stay in the ICU,
      the presence of a CPN was not significantly associated with mortality. Mortality
      rates in the matched cohort (n = 1078) were also similar between patients with
      and without CPNs (89/333 [26.7%] and 226/745 [30.3%], respectively; p = 0.23),
      and the presence of a CPN was not significantly associated with mortality after
      adjustments for potential confounding factors. CONCLUSION: Documenting clinical
      pharmacy activities is essential for assessing pharmacists' impact on patient
      outcomes. These data suggest that ICU pharmacists prioritize clinical activities
      to care for the sickest patients.

PMID- 23950605
TI  - How Many Words Does a Picture Really Tell? Cross-sectional Descriptive Study of
      Pictogram Evaluation by Youth.
AB  - BACKGROUND: Communicating health-related instructions with pictograms is useful,
      but such graphics can be interpreted in different ways. It is crucial to
      understand which pictogram components are best for accurate communication.
      OBJECTIVES: To catalogue pictograms used to label drugs in clinical practice; to
      identify the common graphic elements for defined categories of pictograms, by
      performing a semiotic analysis (studying how signs are perceived and how they
      should be designed); to identify the key graphic elements common to pictograms
      preferred by users; and to develop suggestions for future pictogram design on the
      basis of users' input. METHODS: Literature and Internet searches were performed
      to identify pictograms and pictogram categories. A call for pictograms was also
      circulated through the International Pharmaceutical Federation (FIP). Youth at a
      Canadian pediatric hospital were asked to rate pictograms (including storyboards
      and prescription labels generated by FIP pictogram software) in terms of how best
      they represented their intended meanings. Pictograms for which at least 80% of
      participants "somewhat agreed", "agreed", or "strongly agreed" that the graphic
      conveyed the intended meaning were designated as "preferred" and were selected
      for analysis. Elements appearing in at least 50% of these preferred pictograms
      were highlighted as key graphic elements for design of future pictograms.
      RESULTS: In total, 21 categories were identified for pictograms used in clinical
      practice, and a total of 204 pictograms were analyzed. Eighty-six participants
      took part in the survey. For each pictogram category, certain elements were
      identified as "preferred" and as "key graphic elements", whereas other elements
      met neither designation. For all 21 pictogram categories, at least 80% of survey
      respondents agreed that the FIP storyboard conveyed the intended meaning.
      CONCLUSIONS: Certain key, preferred graphic elements are required for
      pharmaceutical pictograms to convey their intended meaning. The overlap between
      preferred and key pictogram elements indicates that both must be considered in
      development of future pictograms. Redesign of existing pictograms with
      consideration of the best semiotic elements is in progress.

PMID- 23950606
TI  - Vascular protection in patients with diabetes admitted for vascular surgery in a
      canadian tertiary care hospital: pilot study.
AB  - BACKGROUND: Patients with peripheral artery disease are 6 times as likely as
      healthy individuals to die of cardiovascular causes within 10 years after
      diagnosis. Combination therapy with a statin, an angiotensin-converting enzyme
      (ACE) inhibitor or angiotensin II receptor blocker (ARB), and an antiplatelet
      agent is recommended to reduce cardiovascular events in patients with peripheral
      artery disease, especially those with concomitant diabetes mellitus and those who
      have undergone vascular surgery. OBJECTIVES: The primary objective was to
      determine the proportion of patients with concurrent diabetes and peripheral
      artery disease who were receiving therapy with a statin, ACE inhibitor or ARB,
      and antiplatelet agent (acetylsalicylic acid or clopidogrel) at the time of
      discharge after vascular surgery. The secondary objectives were to determine if
      target blood pressure was achieved and if smoking cessation therapy was offered
      and/or provided. METHODS: This pilot study was a retrospective, cross-sectional
      chart analysis. The health records database for Alberta Health Services was
      searched to identify patients with diabetes who underwent vascular surgery at the
      Foothills Hospital in Calgary with discharge between January 1 and June 30, 2010.
      In addition to baseline demographic characteristics, blood pressure values at the
      time of admission and discharge were collected. Discharge medications, including
      cardiovascular medications such as statins, ACE inhibitor or ARB, and
      antiplatelet agents, were recorded. Descriptive analysis of the data was
      performed. RESULTS: Of the 42 patients for whom charts were obtained, 25 (60%)
      had prescriptions for cardiovascular triple therapy (statin, ACE inhibitor or
      ARB, antiplatelet agent). Just over half of the patients (23 [55%]) had achieved
      target blood pressure (< 130/80 mm Hg) at the time of discharge. Of the 14
      current smokers, 9 (64%) had documented evidence in the chart that smoking
      cessation counselling was offered and/or drug therapy was provided. CONCLUSION:
      Only about half of the patients in this study were receiving cardiovascular
      triple therapy, which suggests that many patients were not receiving optimal
      vascular protection. A larger study is needed to review prescribing patterns for
      patients with peripheral artery disease.

PMID- 23950607
TI  - Online versus Live Delivery of Education to Pharmacists in a Large Multicentre
      Health Region: A Non-inferiority Assessment of Learning Outcomes.
AB  - BACKGROUND: The prevalence of online modules for continuing education in the
      health professions has been increasing in recent years. However, the
      effectiveness of online modules for pharmacist learning has not been thoroughly
      studied. OBJECTIVES: The primary aim of this study was to determine if providing
      education to pharmacists through a self-paced enhanced online module was non
      inferior to a face-to-face learning module with respect to knowledge application
      on the topic of postoperative insulin dosing. Secondary aims were to determine
      pharmacists' knowledge gain and retention, as well as their satisfaction with the
      modules. METHODS: The participants in this prospective, randomized, parallel
      group non-inferiority trial were pharmacists in a large multicentre health
      region. Outcomes were measured by comparing scores obtained on pre- and post
      module knowledge-assessment questionnaires. A between-group difference in change
      on knowledge application scores of less than 25 percentage points was the
      predetermined non-inferiority margin. RESULTS: A total of 74 pharmacists
      consented to participate, 38 randomly assigned to use the enhanced online module
      and 36 to attend the face-to-face learning session. For questions examining
      knowledge application, the mean improvement achieved by the online learning group
      was 26 percentage points greater than that achieved by the face-to-face learning
      group (95% confidence interval [CI] 25 to 27; p < 0.001). For questions testing
      knowledge gain, the improvement achieved by the online learning group was 7
      percentage points less than that achieved by the face-to-face learning group (95%
      CI 2 to 12; p = 0.008). Therefore, the enhanced online module was deemed to be
      non-inferior to the face-to-face learning session in terms of knowledge
      application and knowledge gain. Insufficient data were available to analyze the
      secondary outcome of knowledge retention over time. Participant satisfaction was
      similar for the 2 groups (p = 0.62). CONCLUSION: The self-paced enhanced online
      module was non-inferior to facilitated face-to-face learning in terms of
      improving application and knowledge of insulin dosing. Pharmacists had similar
      levels of satisfaction with the 2 modes of learning.

PMID- 23950609
TI  - Erratum: Validity Evidence for FASTHUG-MAIDENS, a Mnemonic for Identifying Drug
      Related Problems in the Intensive Care Unit: Correction.

PMID- 23950608
TI  - [Not Available].
AB  - BACKGROUND: Methylene blue is used in medical practice for various reasons.
      Recent findings point to a potential interaction with serotonin reuptake
      inhibitors (SRIs) that could lead to serotonergic toxicity. OBJECTIVE: To
      describe the risk of serotonergic toxicity associated with the interaction
      between methylene blue and SRIs. DATA SOURCES: Relevant publications were
      searched systematically via MEDLINE (1946 to March 21, 2013) and Embase (1974 to
      2013, week 11) with the following search terms: "methylene blue",
      "methylthioninium", "monoamine oxidase inhibitors", "serotonin reup-take
      inhibitors", and "serotonin syndrome". No restrictions were applied in relation
      to the indication for methylene blue or the language of publication. The
      reference lists of identified articles were also searched. STUDY SELECTION AND
      DATA EXTRACTION: Eighteen case reports and 2 case series were identified for
      inclusion. To date, no randomized controlled trials have been published. DATA
      SYNTHESIS: The first case report indicating suspicion of an interaction between
      methylene blue and SRIs was published in 2003. Seventeen other case reports
      describing the same type of interaction have been published since then. The 2
      case series provided data from about 325 parathyroidectomies in which methylene
      blue was used for staining. The 17 patients who experienced central nervous
      system toxicity were all taking SRIs in the preoperative period. CONCLUSION: When
      administered in combination with SRIs, methylene blue may lead to serotonergic
      toxicity at doses as low as 0.7 mg/kg. Methylene blue would seem to have
      monoamine oxidase A inhibitory properties. Precautions should be taken to avoid
      this interaction. [Publisher's translation].

PMID- 23950610
TI  - Should clinical practitioners, as part of institutional or accreditation
      standards, be required to document their rationale when choosing to not adhere to
      widely accepted clinical practice guidelines?

PMID- 23950611
TI  - Limited role of cockcroft-gault formula in dosing information on product labels
      for antineoplastic drugs.

PMID- 23950612
TI  - Canadian resident research projects and peer-reviewed publication.

PMID- 23950613
TI  - [Not Available].

PMID- 23950614
TI  - "You're Off to Great Places!".

PMID- 23950615
TI  - Coordination in the Science System: Theoretical Framework and a Case Study of an
      Intermediary Organization.
AB  - Many science systems are witnessing the rise of intermediary organizations with a
      coordinating mission, but to date a systematic understanding of their function
      and effects is lacking. The aim of this paper is to contribute to the
      understanding of the coordinating efforts of intermediary organizations. Starting
      from the definition of coordination as the establishment or strengthening of a
      relationship among the activities in a system, with the aim to enhance their
      common effectiveness, I develop a heuristic framework that facilitates the
      systematic analysis of coordination in science. I illustrate and substantiate my
      framework with the empirical case study of a Dutch coordination task force in the
      area of chemical technologies. Thanks to the framework I could disentangle a
      number of functions that this task force fulfils concerning research programming,
      funding allocation and supporting interactions and collaborations. This approach
      enabled me to systematically analyse a very heterogeneous set of processes that
      each deserve to be called coordination. The analysis yields a clear overview of
      eight coordination processes that are each described in terms of activities,
      intervention, relationships, mechanisms and performance. I conclude my paper with
      suggestions for further research on coordination in the science system.

PMID- 23950616
TI  - Stereotype Threat and College Academic Performance: A Latent Variables Approach.
AB  - Stereotype threat theory has gained experimental and survey-based support in
      helping explain the academic underperformance of minority students at selective
      colleges and universities. Stereotype threat theory states that minority students
      underperform because of pressures created by negative stereotypes about their
      racial group. Past survey-based studies, however, are characterized by
      methodological inefficiencies and potential biases: key theoretical constructs
      have only been measured using summed indicators and predicted relationships
      modeled using ordinary least squares. Using the National Longitudinal Survey of
      Freshman, this study overcomes previous methodological shortcomings by developing
      a latent construct model of stereotype threat. Theoretical constructs and
      equations are estimated simultaneously from multiple indicators, yielding a more
      reliable, valid, and parsimonious test of key propositions. Findings additionally
      support the view that social stigma can indeed have strong negative effects on
      the academic performance of pejoratively stereotyped racial-minority group
      members, not only in laboratory settings, but also in the real world.

PMID- 23950617
TI  - Variation of Reproductive Traits and Female Body Size in the Most Widely-Ranging
      Terrestrial Reptile: Testing the Effects of Reproductive Mode, Lineage, and
      Climate.
AB  - The European common lizard, Zootoca vivipara, is the most widespread terrestrial
      reptile in the world. It occupies almost the entire Northern Eurasia and includes
      four viviparous and two oviparous lineages. We analysed how female snout-vent
      length (SVL), clutch size (CS), hatchling mass (HM), and relative clutch mass
      (RCM) is associated with the reproductive mode and climate throughout the species
      range and across the evolutionary lineages within Z. vivipara. The studied
      variables were scored for 1,280 females and over 3,000 hatchlings from 44
      geographically distinct study samples. Across the species range, SVL of
      reproductive females tends to decrease in less continental climates, whereas CS
      corrected for female SVL and RCM tend to decrease in climates with cool summer.
      Both relationships are likely to indicate direct phenotypic responses to climate.
      For viviparous lineages, the pattern of co-variation between female SVL, CS and
      HM among populations is similar to that between individual females within
      populations. Consistent with the hypothesis that female reproductive output is
      constrained by her body volume, the oviparous clade with shortest retention of
      eggs in utero showed highest HM, the oviparous clade with longer egg retention
      showed lower HM, and clades with the longest egg retention (viviparous forms) had
      lowest HM. Viviparous populations exhibited distinctly lower HM than the other
      European lacertids of similar female SVL, many of them also displaying unusually
      high RCM. This pattern is consistent with Winkler and Wallin's model predicting a
      negative evolutionary link between the total reproductive investment and
      allocation to individual offspring.

PMID- 23950618
TI  - Lack of Evidence of Simian Immunodeficiency Virus Infection Among Nonhuman
      Primates in Tai National Park, Cote d'Ivoire: Limitations of Noninvasive Methods
      and SIV Diagnostic Tools for Studies of Primate Retroviruses.
AB  - It is now well established that the human immunodeficiency viruses, HIV-1 and HIV
      2, are the results of cross-species transmissions of simian immunodeficiency
      viruses (SIV) naturally infecting nonhuman primates in sub-Saharan Africa. SIVs
      are found in many African primates, and humans continue to be exposed to these
      viruses by hunting and handling primate bushmeat. Sooty mangabeys (Cercocebus
      atys) and western red colobus (Piliocolobus badius badius) are infected with SIV
      at a high rate in the Tai Forest, Cote d'Ivoire. We investigated the SIV
      infection and prevalence in 6 other monkey species living in the Tai Forest using
      noninvasive methods. We collected 127 fecal samples from 2 colobus species
      (Colobus polykomos and Procolobus verus) and 4 guenon species (C. diana, C.
      campbelli, C. petaurista, and C. nictitans). We tested these samples for HIV
      cross-reactive antibodies and performed reverse transcriptase-polymerase chain
      reactions (RT-PCR) targeting the gag, pol, and env regions of the SIV genome. We
      screened 16 human microsatellites for use in individual discrimination and
      identified 4-6 informative markers per species. Serological analysis of 112
      samples yielded negative (n=86) or uninterpretable (n=26) results. PCR analysis
      on 74 samples confirmed the negative results. These results may reflect either
      the limited number of individuals sampled or a low prevalence of infection.
      Further research is needed to improve the sensitivity of noninvasive methods for
      SIV detection.

PMID- 23950619
TI  - Efficient sorption of polyphenols to soybean flour enables natural fortification
      of foods.
AB  - The present study demonstrated that defatted soybean flour (DSF) can sorb
      polyphenols from blueberry and cranberry juices while separating them from
      sugars. Depending on DSF concentration and juice dilution, the concentration of
      blueberry anthocyanins and total polyphenols sorbed to DSF ranged from 2 - 22
      mg/g and 10 - 95 mg/g, respectively while the concentration of anthocyanins and
      proanthocyanidins in cranberry polyphenol-enriched DSF ranged from 2.5 - 17 mg/g
      and 21 - 101 mg/g, respectively. Blueberry polyphenols present in one serving of
      fresh blueberries (73g) were delivered in just 1.4 g of blueberry polyphenol
      enriched DSF. Similarly, one gram of cranberry polyphenol-enriched DSF delivered
      the amount of proanthocyanidins available in three 240 ml servings of cranberry
      juice cocktail. The concentration of blueberry anthocyanins and total polyphenols
      eluted from DSF remained constant after 22 weeks of incubation at 37 degrees C,
      demonstrating the high stability of the polyphenol-DSF matrix. LC-MS analysis of
      eluates confirmed DSF retained major cranberry and blueberry polyphenols remained
      intact. Blueberry polyphenol-enriched DSF exhibited significant hypoglycemic
      activities in C57bl/6J mice, and cranberry polyphenol-enriched DSF showed anti
      microbial and anti-UTI activities in vitro, confirming its efficacy. The
      described sorption process provides a means to create protein-rich food
      ingredients containing concentrated plant bioactives without excess sugars, fats
      and water that can be incorporated in a variety of scientifically validated
      functional foods and dietary supplements.

PMID- 23950620
TI  - Single fiber laser based wavelength tunable excitation for CRS spectroscopy.
AB  - We demonstrate coherent Raman spectroscopy (CRS) using a tunable excitation
      source based on a single femtosecond fiber laser. The frequency difference
      between the pump and the Stokes pulses was generated by soliton self-frequency
      shifting (SSFS) in a nonlinear optical fiber. Spectra of C-H stretches of
      cyclohexane were measured simultaneously by stimulated Raman gain (SRG) and
      coherent anti-Stokes Raman scattering (CARS) and compared. We demonstrate the use
      of spectral focusing through pulse chirping to improve CRS spectral resolution.
      We analyze the impact of pulse stretching on the reduction of power efficiency
      for CARS and SRG. Due to chromatic dispersion in the fiber-optic system, the
      differential pulse delay is a function of Stokes wavelength. This differential
      delay has to be accounted for when performing spectroscopy in which the Stokes
      wavelength needs to be scanned. CARS and SRG signals were collected and displayed
      in two dimensions as a function of both the time delay between chirped pulses and
      the Stokes wavelength, and we demonstrate how to find the stimulated Raman
      spectrum from the two-dimensional plots. Strategies of system optimization
      consideration are discussed in terms of practical applications.

PMID- 23950623
TI  - Another season of graduation.

PMID- 23950621
TI  - Making no bones about it: Transcription factors in vertebrate skeletogenesis and
      disease.
AB  - Skeletogenesis is a complex multi-step process, which involves many genes and
      pathways. The tightly regulated interplay between these genes in these pathways
      ensures a correct and timely organogenesis and it is imperative that we have a
      fair understanding of the major genes and gene families involved in the process.
      This review aims to give a deeper insight into the roles of 3 major transcription
      factor families involved in skeleton formation: Sox, Runx and Pax and to look at
      the human skeleotogenic phenotypes associated with mutations in these genes.

PMID- 23950622
TI  - Quantile Regression for Competing Risks Data with Missing Cause of Failure.
AB  - This paper considers generalized linear quantile regression for competing risks
      data when the failure type may be missing. Two estimation procedures for the
      regression co-efficients, including an inverse probability weighted complete-case
      estimator and an augmented inverse probability weighted estimator, are discussed
      under the assumption that the failure type is missing at random. The proposed
      estimation procedures utilize supplemental auxiliary variables for predicting the
      missing failure type and for informing its distribution. The asymptotic
      properties of the two estimators are derived and their asymptotic efficiencies
      are compared. We show that the augmented estimator is more efficient and
      possesses a double robustness property against misspecification of either the
      model for missingness or for the failure type. The asymptotic covariances are
      estimated using the local functional linearity of the estimating functions. The
      finite sample performance of the proposed estimation procedures are evaluated
      through a simulation study. The methods are applied to analyze the 'Mashi' trial
      data for investigating the effect of formula-versus breast-feeding plus extended
      infant zidovudine prophylaxis on HIV-related death of infants born to HIV
      infected mothers in Botswana.

PMID- 23950624
TI  - Utilization of clean and safe delivery service package of health services
      extension program and associated factors in rural kebeles of Kafa Zone, Southwest
      Ethiopia.
AB  - BACKGROUND: In Ethiopia, 94% of births take place at home unattended by trained
      persons. The government introduced an innovative strategy, Health Services
      Extension Program in 2003. Clean and safe delivery service is a component of
      maternal and child healthcare package of the program. However, little is known
      about the status of uptake of the service. This study thus aimed to assess
      utilization of clean and safe delivery service and associated factors in rural
      kebeles of Kafa Zone, Ethiopia. METHODS: A community based cross sectional survey
      was conducted in rural kebeles of Kefa Zone from January 21(st) to February
      25(th), 2009 using a sample of 229 mothers. Kafa Zone is located 465 kilometres
      away from Addis Ababa to southwest of Ethiopia. Data were collected using a
      structured questionnaire and analyzed using SPSS for windows version 16. OR and
      95% CI were calculated. P< 0.05 was considered statistically significant.
      RESULTS: Utilization of clean and safe delivery service was 43(19%). Women with
      formal schooling and those who knew at least two danger signs of pregnancy and
      labor were more likely to use the service than their counterparts; (AOR=5.8, 95%
      CI=2.1, 16) and (AOR=3.0, 95% CI=2.2, 10.6), respectively. Of 108(47.8%) mothers
      who had at least one antenatal care visit, 36(33.3%), were not advised about
      danger signs. Women who had at least one ANC visit and those who were advised
      about the danger signs of pregnancy and labor appeared to be more likely to use
      the service than their counterparts; (AOR=6.1, 95% CI=1.9, 21.3), and (AOR=5.4,
      95%CI= 1.4, 21.7), respectively. CONCLUSION: Utilization of the service is low
      and was determined by women's educational status, history of abortion, knowledge
      of danger signs and antenatal care attendance. Educating women and improving
      their knowledge about danger signs of pregnancy and labor is recommended. Health
      extension workers should consider antenatal care visits as opportunities for this
      purpose.

PMID- 23950625
TI  - Calcium, magnesium, iron, zinc and copper, compositions of human milk from
      populations with cereal and 'enset' based diets.
AB  - BACKGROUND: As breast milk is normally the only source of food in the early
      stages of life, the dietary levels of the essential elements in the milk of
      lactating mothers are significantly important. Ethiopia is a country of many
      nations and nationalities with distinct dietary habits. This variation in food
      habit may result in the variation of the nutritional quality of milk of lactating
      mothers who live in different part of the country, which in turn may affect the
      intake of nutrients by breast-fed infants. Therefore, a cross-sectional study of
      the levels of Ca, Mg, Fe, Zn and Cu in milk of mothers from societies with cereal
      and 'enset' based dietary habits was carried out to assess the influence of
      maternal diet on the levels of the elements in human milk. METHODS: Milk samples
      were collected from 27 voluntary mothers in Jimma and in 18 rural areas of
      Welkite. Breast milk samples were collected within four days postpartum and the
      concentrations of the elements were determined by using FAAS. RESULTS: Average
      concentrations (mg/L) of the elements determined in the milk of mothers from
      Jimma and rural Welkite respectively were: Ca (758 +/- 107, 579 +/- 168); Mg
      (22.6 +/- 7.87, 30.5 +/- 13.4); Fe (0.50 +/- 0.08, 0.41 +/- 0.17); Zn (2.3 +/-
      1.2, 2.49 +/- 0.88) and Cu (0.28 +/- 0.14, 0.16 +/- 0.08). CONCLUSIONS: Milk
      samples from Jimma were found to have significantly higher levels of Ca and Cu
      than those of rural Welkite (P < 0.05). Breast milk Ca and Cu levels were thus
      found to be influenced by dietary intake.

PMID- 23950626
TI  - Associations between academic stressors, reaction to stress, coping strategies
      and musculoskeletal disorders among college students.
AB  - BACKGROUND: The adverse health effects of stress are enormous, and vary among
      people, probably because of differences in how stress is appraised and the
      strategies individuals use to cope with it. This study assessed the association
      between academic stress and musculoskeletal disorders (MSDs) among 1365
      undergraduates. METHODS: This was a cross-sectional study conducted in a Nigerian
      university at the beginning of the 2010/2011 academic session with the same group
      of participants. The Life Stress Assessment Inventory, Coping Strategies
      Questionnaire, and Short Musculoskeletal Function Assessment were administered as
      tools of data gathering. RESULTS: Students' stress level and associated MSDs were
      higher during the examination period than the pre-examination periods. Stressors
      were significantly associated with increased risk of MSDs in both sexes were
      those related to changes (odds ratio (OR) = 1.7, p = 0.002) and pressures (OR =
      2.09, p = 0.001). Emotional and physiological reactions to stress were
      significantly associated with MSDs in both sexes, with higher odds for MSDs in
      females, whereas cognitive and behavioral reactions showed higher odds (though
      non-significant) in males. The risk of MSDs was higher in respondents who adopted
      avoidance and religious coping strategies compared with those who adopted active
      practical and distracting coping strategies. CONCLUSIONS: Stress among students
      could be significantly associated with MSDs depending on individuals'
      demographics, stressors, reactions to stress, and coping methods. Interventions
      to reduce stress-induced MSDs among students should consider these factors among
      others.

PMID- 23950627
TI  - Empathy without borders? Cross-cultural heart and mind-reading in first-year
      medical students.
AB  - BACKGROUND: This cross-cultural study was designed to examine cultural
      differences in empathy levels of first-year medical students. METHODS: A total of
      257 students from the academic year 2010/11, 131 at Jimma University, Ethiopia,
      and 126 at the Ludwig Maximilian University, Munich, Germany, completed the
      Balanced Emotional Empathy Scale (BEES), the Reading the Mind in the Eyes (RME-R)
      test, and a questionnaire on sociodemographic and cultural characteristics.
      Furthermore, we conducted a qualitative analysis of the students' personal views
      on the definition of empathy and possible influencing factors. Group comparisons
      and correlation analyses of empathy scores were performed for the entire cohort
      and for the Jimma and Munich students separately. We used a regression tree
      analysis to identify factors influencing the BEES. RESULTS: The male students in
      Jimma (39.1 +/- 22.3) scored significantly higher in the BEES than those male
      students from Munich (27.2 +/- 22.6; p = 0.0002). There was no significant
      difference between the female groups. We found a moderate, positive correlation
      between the BEES and RME-R test, i.e. between emotional and cognitive empathy,
      within each university. Nevertheless, the RME-R test, which shows only Caucasian
      eyes, appears not to be suitable for use in other cultures. CONCLUSIONS: The main
      findings of our study were the influence of culture, religion, specialization
      choice, and gender on emotional empathy (assessed with the BEES) and cognitive
      empathy (assessed with the RME-R test) in first-year medical students. Further
      research is required into the nature of empathy in worldwide medical curricula.

PMID- 23950628
TI  - Association between khat chewing and gastrointestinal disorders: a cross
      sectional study.
AB  - BACKGROUND: Khat (Catha edulis Forsk) is a psycho-stimulant substance grown in
      East Africa. But its adverse effects and its prevalence are not well studied. The
      main aim of the present study is thus to assess the association between khat
      chewing and GI problems among students in Ambo University. METHODS: A cross
      sectional study was conducted in January 2010 on 1005 Ambo University students.
      Study subjects were selected using systematic random sampling technique, and data
      were collected using self-administered questionnaire. Data analysis was made
      using SPSS version 16.0 for windows package. RESULTS: The mean age of the
      respondents was 20.79 +/- 1.39 ranging from 18-30 years. Seven hundred twenty
      (71.6 %) of the study participants were males and 994 (98.9%) were in the age
      group of 15-24 years. The prevalence of gastritis was 580 (57.7%); constipation
      235 (23.4%); hemorrhoids 54 (5.4%) and that of dental problems (carries, decay,
      filling and extraction) was 225 (22.4%) of all study participants.
      Gastrointestinal disorders were found to be higher among khat chewers, where
      64(36.2%) of them had dental problems; 127(71.8%) symptoms of gastritis;
      86(48.6%) constipation and 26(14.7%) hemorrhoids which demonstrated statistically
      significant association with p < 0.001. CONCLUSION: The prevalence of
      gastrointestinal disorders was found to be higher among khat chewers, indicating
      that khat chewing could be a predisposing factor to gastrointestinal disorders.
      Community-based awareness creation about the adverse effect of khat use is thus
      recommended.

PMID- 23950629
TI  - Evaluation of community-based trichiasis surgery in Northwest Ethiopia.
AB  - BACKGROUND: Surgery to correct trachomatous trichiasis (TT) is recommended to
      prevent blindness caused by trachoma. This study evaluated the outcomes of
      community-based trichiasis surgery with absorbable sutures, conducted in Amhara
      Regional State, Ethiopia. METHODS: A simple random sample of 431 patients was
      selected from surgical campaign records of which 363 (84.2%) were traced and
      enrolled into the study. Participants were interviewed and examined for
      trichiasis recurrence, complications of TT surgery and corneal opacity.
      Multilevel logistic regression models were used to explore the associations
      between trichiasis recurrence, corneal opacity and explanatory variables at the
      eye level. RESULTS: The prevalence of trichiasis recurrence was 9.4% (95%
      Confidence Interval [CI] 6.6-12.8) and corneal opacity was found in 14.3% (95% CI
      10.9-18.3) of the study participants. The proportion of participants with
      complications of TT surgery was: granuloma 0.6% (95% CI 0.1-2.0); lid closure
      defects 5.5% (95% CI 3.4-8.4) and lid notching 16.8% (95% CI 13.1-21.1). No
      factors were identified for trichiasis recurrence. Corneal opacity was associated
      with increased age (Ptrend=0.001), more than 12 months post surgery (OR=2.7;
      95%CI 1.3-5.6), trichiasis surgery complications (OR=2.9; 95%CI 1.4-5.9) and
      trichiasis recurrence (OR=2.5; 95%CI 1.0-6.3). CONCLUSION: Prevalence of
      recurrent trichiasis and granuloma were lower than expected but higher for lid
      closure defects and lid notching. The majority of the participants reported
      satisfaction with the trichiasis surgery they had undergone. The findings suggest
      that recurrence of trichiasis impacts on the patients' risk of developing corneal
      opacity but longitudinal studies are required to confirm this.

PMID- 23950630
TI  - Pattern of pathogens and their sensitivity isolated from surgical site infections
      at the Aga Khan University Hospital, Nairobi, Kenya.
AB  - BACKGROUND: In low income countries, surgical site infections (SSIs) are costly
      and impose a heavy and potentially preventable burden on both patients and
      healthcare providers. This study aimed to determine the occurrence of SSI,
      pathogens associated with SSI, the antibiogram of the causative pathogens and
      specific risk factors associated with SSI at the hospital. METHODS: Two hundred
      and sixty-eight respondents admitted for general surgical procedures (other than
      neurological and cardiothoracic surgeries) at the Aga Khan University Hospital
      were eligible to take part in the study. Post-surgery patients were observed for
      symptoms of infection. Follow ups were done through the consulting clinics,
      breast clinic and casualty dressing clinic by a team of surgeons. In cases of
      infection, pus swabs were collected for culture. RESULTS: SSI incidence rate was
      7.0%, pathogens isolated from SSI included gram negative enteric bacilli and S.
      aureus which was the most prevalent bacterial isolate. Only one isolate of MRSA
      was found and all staphylococci were susceptible to Vancomycin. Preoperative stay
      >= 2 days and wound class were the risk factors associated with SSI. CONCLUSION:
      The SSI incidence rates (7.0%) observed in this study were relatively lower than
      the ones documented in other studies in Kenya. S. aureus is the most prevalent
      pathogen associated with SSI. Similar to findings from other studies done in the
      region; prolonged hospital stay and dirty wounds were the risks associated with
      postsurgical sepsis at the hospital.

PMID- 23950631
TI  - Relationship between family history of breast cancer and clinicopathological
      features in Moroccan patients.
AB  - BACKGROUND: Breast cancer is the most common cancer affecting women all over the
      world. In addition to hormonal and environmental causes, family history is
      emerging as an important risk factor in the etiology of this disease. The aim of
      the present study is thus to compare the clinico-pathological features of
      familial and sporadic breast cancer in Moroccan patients. METHODS: A comparative
      retrospective cohort study was conducted on 570 women with familial and sporadic
      breast cancer who were diagnosed and treated in the Oncology Center of Ibn Rochd
      University Hospital in 2009. Data on breast cancer risk factors and clinico
      pathological characteristics of the tumors were extracted from patients' medical
      records. RESULTS: Familial cases represented 18.4% of breast cancer patients. The
      age of onset appears to be earlier in familial breast cancers (P=0.0024). There
      were no significant differences between familial and sporadic groups according to
      histological type, tumor size and estrogen receptor status. However, Scarff-Bloom
      Richardson grade III was found in 43.8% of familial cases vs 26.7% of sporadic
      cases (P=0.0127) and the lymph node involvement was observed in 72.4% of familial
      cases vs 58.9% in sporadic cases (P=0.0213). Moreover, familial breast cancer
      patients present especially progesterone receptor-negative tumors (P=0.0380).
      CONCLUSIONS: Our initial significant findings show that familial breast cancer
      seems to affect young women and tends to present high Scarff-Bloom-Richardson
      grade tumors with lymph node involvement and absence of progesterone receptors.
      These preliminary results may be useful as clinical marker to identify familial
      breast cancer allowing the development of careful follow-up for this patients
      subtype.

PMID- 23950632
TI  - Patients' attitude towards medical students involvement in their health care at
      Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia, 2010.
AB  - BACKGROUND: Patients' willingness to the involvement of medical students in their
      health care is the mandatory input to medical education. Admitted patients'
      willingness level should be known and factors affecting willingness should be
      identified and it is necessary to act upon them for better medical care.
      METHODOLOGY: A cross-sectional hospital based survey was conducted to assess the
      admitted patients' attitude towards medical students' involvement in their health
      care at Tikur Anbesa Specialized Hospital in 2010. Data were collected from 422
      adult patients admitted in Tikur Anbesa Specialized Hospital from April to May
      2010 using structured questionnaire and by interview method. The data gathered in
      this way were then processed using SPSS version 15. RESULT: Three hundred and
      ninety-two participants had responded to all questions they were asked (response
      rate = 92.8%). One hundred and five (26.8%) patients had negative attitude to
      medical students' involvement in their health care. The proportion of patients'
      having positive attitude towards students was slightly reduced from medical to
      surgical and to gynecology wards 77.4%, 72.0%, 69.2% respectively. Patients who
      had previous interactions with students were more likely to have negative
      attitude (AOR (95% CI) = 1.72(1.03, 2.87). The odds patients admitted in
      gynecology and obstetrics ward to prefer female students to care for them was
      higher (AOR (95% CI) =1.93(1.13, 3.30). CONCLUSION: Almost half of the patients
      admitted to Tikur Anbessa Specialized Hospital objected to clinical procedures on
      them even physical examination, hence developing clinical skills in TASH might be
      challenging for the majority of students. The challenge might be worsened for
      male students in gynecology wards.

PMID- 23950633
TI  - Magnitude of anemia and associated risk factors among pregnant women attending
      antenatal care in Shalla Woreda, West Arsi Zone, Oromia Region, Ethiopia.
AB  - BACKGROUND: Anemia during pregnancy is a common problem in developing countries
      and affects both the mother's and her child's health. The main objective of this
      study was to determine the prevalence of and the factors associated with anemia
      among pregnant women. METHODS: Facility based cross-sectional study design was
      conducted from June to August, 2011 on 374 pregnant women. Mothers who came for
      ANC during the study period and who met the inclusion criteria were interviewed
      and a capillary blood sample was taken. Hemoglobin level was determined by using
      HemoCue photometer, and interviewer administered questionnaire was used to
      collect data. Data were cleaned, coded and fed into SPSS version 16.0 for
      analysis. RESULT: The mean hemoglobin concentration was 12.05+/-1.5 g/dl and
      prevalence of anemia was 36.6%. Family sizes (COR=2.67, CI (1.65, 4.32), third
      trimester (COR=1.45, CI (1.11, 2.23), meat consumption <1x/wk (COR=3.47, CI
      (1.58, 7.64) and pica (COR=2.33, CI (1.52, 3.58) were significantly associated
      with anemia. Having five or more children (AOR=5.2, CI [1.29, 21.09]), intake of
      vegetables and fruits less than once per day (AOR= 6.7, CI [2.49, 17.89]), intake
      of tea always after meal (AOR = 12.83.CI [45-28.9]), and recurrence of illness
      during pregnancy (AOR=7.3, CI [2.12-25.39]) were factors associated with anemia.
      CONCLUSION: This study showed that anemia is a moderate public health problem.
      Less frequent meat and vegetable consumption, parity >=5 are risk factors for
      anemia. Therefore, reducing parity, taking balanced diet and use of mosquito nets
      during pregnancy are recommended.

PMID- 23950634
TI  - Rare occurrence of mix stromal tumours: a case report of gastrointestinal and
      extra-intestinal stromal tumour on the jejunum and omentum of a nine year old
      girl from Adamawa State, Nigeria.
AB  - BACKGROUND: Stromal tumors of the jejunum (GIST) and omentum (EGIST) are uncommon
      and dearth of information still exists on their occurrence concurrently. CASE
      DETAILS: Here, we report a nine year old girl that presented with tender
      abdominal mass measuring 14 * 8 cm associated with features of gastric outlet
      obstruction and hyponatremia of 115mmol/L. A diagnosis of hyponatremia in a child
      with gastric outlet obstruction secondary to intraabdominal mass was made for
      which exploratory laparotomy was carried out. Histology of the tumour revealed
      stromal spindle epithelioid as well as myxoid cells. Complete resection of the
      tumour and correction for hyponatremia was done in addition to antibiotics
      therapy with remarkable improvement. CONCLUSION: Index case is that of mixed
      stromal tumours that presented with features of gastric outlet obstruction, and
      the patient did well after surgery.

PMID- 23950635
TI  - Oral focal mucinosis: a rare case report of two cases.
AB  - Oral focal mucinosis (OFM) is a rare soft tissue lesion of unknown etiology.
      Clinically, it is most commonly found on the gingiva and presents as a painless,
      sessile or pedunculated mass of the same colour as the surrounding mucosa.
      Histologically, it is characterized by focal myxoid degeneration of connective
      tissue. OFM occurs predominantly in adults during the fourth and fifth decade of
      life, although it has been reported infrequently in children and adolescents. Its
      diagnosis mainly relies on histological analysis and the treatment involves
      complete surgical excision. Its recurrence is unreported. The aim of this report
      of two cases is to describe the clinical and histological presentation and
      subsequent management of OFM. The cause of OFM remains unknown. The cases
      presented in this report bring OFM to the attention of anatomical pathologists
      while considering the differential diagnosis of myxoid lesions of the oral
      cavity. 

PMID- 23950636
TI  - Plasma cell gingivitis associated with inflammatory chelitis: a report on a rare
      case.
AB  - BACKGROUND: Plasma cell gingivitis (PGC) is a rare disease of gingival tissues
      which is difficult to treat. It has a higher rate of reoccurrence and needs a
      detailed and careful analysis of etiology. Further, its association with chelitis
      is rare, only few cases have been reported and the condition with this
      presentation poses a diagnostic dilemma. CASE REPORT: This paper reports a 16
      year old male with a complaint of bleeding and swelling of gingiva since 3 years.
      The gingival enlargement occurred on facial aspect of upper and lower anterior
      teeth involving attached gingival. He also presented with swelling of both lips
      which was recurrent and for the same duration of 3 years. DISCUSSION: Based on
      clinical features and histopathological findings, a diagnosis of plasma cell
      gingivitis with inflammatory chelitis was made. A detailed history of possible
      allergen exposure was taken and patch test was conducted to identify any such
      allergens. Other conditions were ruled out by blood investigation, detailed
      medical and drug history. CONCLUSION: A close collaboration between Periodontist
      and Dermatologist is essential to manage such a case.

PMID- 23950637
TI  - Sewer Gas: An Indoor Air Source of PCE to Consider During Vapor Intrusion
      Investigations.
AB  - The United States Environmental Protection Agency (USEPA) is finalizing its vapor
      intrusion guidelines. One of the important issues related to vapor intrusion is
      background concentrations of volatile organic chemicals (VOCs) in indoor air,
      typically attributed to consumer products and building materials. Background
      concentrations can exist even in the absence of vapor intrusion and are an
      important consideration when conducting site assessments. In addition, the
      development of accurate conceptual models that depict pathways for vapor entry
      into buildings is important during vapor intrusion site assessments. Sewer gas,
      either as a contributor to background concentrations or as part of the site
      conceptual model, is not routinely evaluated during vapor intrusion site
      assessments. The research described herein identifies an instance where vapors
      emanating directly from a sanitary sewer pipe within a residence were determined
      to be a source of tetrachloroethylene (PCE) detected in indoor air.
      Concentrations of PCE in the bathroom range from 2.1 to 190 ug/m3 and exceed
      typical indoor air concentrations by orders of magnitude resulting in human
      health risk classified as an "Imminent Hazard" condition. The results suggest
      that infiltration of sewer gas resulted in PCE concentrations in indoor air that
      were nearly two-orders of magnitude higher as compared to when infiltration of
      sewer gas was not known to be occurring. This previously understudied pathway
      whereby sewers serve as sources of PCE (and potentially other VOC) vapors is
      highlighted. Implications for vapor intrusion investigations are also discussed.

PMID- 23950638
TI  - Development of a novel disposable lid speculum with a drape.
AB  - PURPOSE: To evaluate the clinical use of a newly-developed disposable lid
      speculum with a drape. METHODS: LiDrape(r) is a cylindrical device that consists
      of two flexible rings of polyacetal resin with a transparent elastic silicone
      sheet attached to the rings. The novel device holds the eyelids between the
      rings, and a hole in the center of the device provides a surgical field. We used
      the novel device in cataract surgery (75 eyes), glaucoma surgery (eleven eyes),
      vitrectomy (ten eyes), and intravitreal injection (six eyes) and evaluated its
      clinical efficacy. RESULTS: The LiDrape was easy to attach and detach. The novel
      device was not detached from the eye during surgery. No eyelashes or secretions
      from the meibomian glands were seen in the surgical field, and the drape provided
      a sufficient surgical field. CONCLUSIONS: The LiDrape functions as a lid speculum
      as well as a drape. Our results showed that the novel device is useful for ocular
      surgeries.

PMID- 23950639
TI  - Renal thrombotic microangiopathy caused by interferon beta-1a treatment for
      multiple sclerosis.
AB  - Interferon beta-1a is available as an immunomodulating agent for relapsing forms
      of multiple sclerosis. Common side effects include flu-like symptoms, asthenia,
      anorexia, and administration site reaction. Kidney disorders are rarely reported.
      In this study we describe the case of a woman who has been undergoing treatment
      with interferon beta-1a for multiple sclerosis for 5 years. She developed a
      hemolytic-uremic syndrome with intravascular hemolysis in a context of severe
      hypertension. A kidney biopsy showed a thrombotic microangiopathy. This
      observation highlights an uncommon side effect of long-term interferon beta-1a
      therapy. Pathophysiological mechanisms leading to this complication might be
      explained by the antiangiogenic activity of interferon. 

PMID- 23950640
TI  - Physical performance in recently aged adults after 6 weeks traditional Thai
      dance: a randomized controlled trial.
AB  - BACKGROUND: Exercise has been shown to be effective in cardiovascular endurance
      in the elderly. We studied the effect of Thai dancing on physical performance of
      Thai elderly. METHODS: This was an open-labeled, randomized intervention study.
      The Thai dancing group exercised for 40 minutes three times a week for 6 weeks.
      Physical performance ability was the primary outcome, including a 6-minute walk
      test (6MWT), five-times sit-to-stand (FTSST), and a sit-and-reach test measured
      before and after 6 weeks of intervention. RESULTS: There were 42 subjects
      enrolled in the study, and 38 female subjects completed (20 in Thai dance group,
      18 controls), with an average age of 65.8 +/- 5.1 years. The Thai dance group had
      significantly better physical performance in all measurements at the end of the
      study. The 6MWT was longer (416.7 +/- 58.7 versus 345.7 +/- 55.1 m; P = 0.011),
      FTSST was quicker (10.2 +/- 1.5 versus 14.4 +/- 3.3 seconds; P < 0.001), and
      flexibility was higher (14.9 +/- 3.5 versus 11.1 +/- 5.7 cm; P = 0.002) in the
      Thai dance group than the control group. CONCLUSION: Thai dance can improve
      physical performance in recently aged (elderly) female adults.

PMID- 23950641
TI  - Effectiveness of alteplase in the very elderly after acute ischemic stroke.
AB  - Alteplase has traditionally been the only pharmacologic agent available for
      treating acute ischemic stroke worldwide, and is considered an effective and safe
      therapeutic drug for acute cerebral ischemia. However, the drug is usually
      indicated for use in patients aged <81 years due to insufficient literature
      regarding the drug's safety in older individuals. Nevertheless, the elderly can
      benefit from alteplase after they experience an acute ischemic stroke. Age
      differences have been observed in the clinical presentation of acute ischemic
      stroke; however, the safety and efficacy of alteplase for patients with acute
      ischemic stroke do not depend on age or sex. Evidence of an increasing rate of
      intracerebral hemorrhage among the elderly with acute ischemic stroke, following
      alteplase treatment, has not been reported. Severe intracranial hemorrhage is a
      known side effect of alteplase but is not associated with age in patients with
      acute ischemic stroke. Alteplase can be used safely and effectively to treat
      elderly patients who suffer an acute ischemic stroke, including those over the
      age of 80 years. 

PMID- 23950642
TI  - Effect of Memo(r), a natural formula combination, on Mini-Mental State
      Examination scores in patients with mild cognitive impairment.
AB  - BACKGROUND: Mild cognitive impairment encompasses the clinical continuum between
      physiologic age-related cognitive changes and dementia. A variety of medications,
      including herbal preparations (in particular Ginkgo biloba and Panax ginseng),
      have been advocated as treatments for cognitive impairment in the elderly. In
      this study, we investigated the effect of an already marketed dietary supplement
      (Memo(r)) combining 750 mg of lyophilized royal jelly with standardized extracts
      of G. biloba 120 mg and P. ginseng 150 mg on Mini-Mental State Examination (MMSE)
      scores in patients with mild cognitive impairment. METHODS: Sixty-six subjects
      presenting with forgetfulness and satisfying the Diagnostic and Statistical
      Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) clinical
      criteria for mild cognitive impairment were randomly divided into an experimental
      group treated with one Memo capsule before breakfast daily for 4 weeks and a
      control group who took placebo. The mean change in MMSE score from baseline and
      reported adverse effects were compared between the two groups. RESULTS: The mean
      change in MMSE score in the group treated with Memo for 4 weeks was significantly
      greater than in the control group (+2.07 versus +0.13, respectively) by the
      Student's t-test (t = 6.485, P < 0.0001). This was also true after adjusting for
      age as a covariate and educational level as a factor nested within the treatment
      groups in a general linear model (analysis of covariance, F = 9.675 [corrected
      model], P < 0.0001). CONCLUSION: This combined triple formula may be beneficial
      in treating the cognitive decline that occurs during the aging process as well as
      in the early phases of pathologic cognitive impairment typical of insidious-onset
      vascular dementia and in the early stages of Alzheimer's disease. Larger-sized
      studies with longer treatment durations are needed to confirm this.

PMID- 23950644
TI  - Influence of rs1080985 single nucleotide polymorphism of the CYP2D6 gene on
      response to treatment with donepezil in patients with alzheimer's disease.
AB  - BACKGROUND: Recent data indicate that the rs1080985 single nucleotide
      polymorphism of the cytochrome P450 (CYP) 2D6 gene may affect the response to
      treatment with donepezil in patients with Alzheimer's disease. There is also
      evidence that the common apolipoprotein E (APOE) polymorphism may affect the
      response to treatment with donepezil in Alzheimer's disease. We investigated the
      association between response to donepezil and the rs1080985 single nucleotide
      polymorphism, the minor allele (G) of which was previously reported to be
      associated with a poor response to this drug in patients with Alzheimer's
      disease. The common APOE polymorphism was also assessed for its relevance to the
      outcome of this treatment. METHODS: Analysis of CYP2D6 and APOE polymorphisms was
      undertaken in 88 naive Caucasian patients with Alzheimer's disease. All patients
      received treatment with donepezil for at least 10 months, and the response to
      treatment was then assessed according to the National Institute for Health and
      Clinical Excellence criteria. RESULTS: No significant differences were observed
      in distribution of the CYP2D6 rs1080985 single nucleotide polymorphism or common
      APOE polymorphism between responders (68.2%) and nonresponders (31.8%) to
      treatment with donepezil. CONCLUSION: Our results suggest that neither the CYP2D6
      nor the APOE polymorphism influences the response to treatment with donepezil in
      a Polish population with Alzheimer's disease.

PMID- 23950645
TI  - Efficacy and tolerability of pramipexole for the treatment of primary restless
      leg syndrome: a meta-analysis of randomized placebo-controlled trials.
AB  - Primary restless leg syndrome (RLS) is a common sensory-motor disorder that is
      characterized by an irresistible urge to move the limbs and unpleasant sensations
      in the legs, which affects 1.9%-4.6% adults. Pramipexole, a potent dopamine D2/3
      agonist, is recommended as "effective" in the short-term and "possibly effective"
      in the long-term treatment of primary RLS in the European guidelines on
      management of RLS. In this meta-analysis, we summarized the efficacy and
      tolerability of pramipexole in treatment for primary RLS. Results of this meta
      analysis showed a favorable effect of pramipexole versus placebo on RLS symptoms
      (mean change on International RLS Study Group Rating Scale [IRLS] score: mean
      difference [MD] = -5.96; 95% confidence interval [CI]: -7.79 to -4.41, P <
      0.00001) and sleep quality (pooled standard mean difference [SMD] = -0.48, 95%
      CI: -0.61 to -0.35, P < 0.00001). Nausea (relative risk [RR] = 2.68, 95% CI: 1.82
      to 3.95, P < 0.001) and fatigue (RR = 1.82, 95% CI: 1.14 to 2.93, P = 0.013) were
      the most common adverse events, but, by and large, pramipexole was well-tolerated
      in patients with primary RLS. Nevertheless, long-term studies and more evidence
      of head-to-head comparisons of pramipexole with other dopamine agonists,
      anticonvulsants, and levodopa are needed. 

PMID- 23950643
TI  - How nanotechnology can enhance docetaxel therapy.
AB  - Docetaxel has been recognized as one of the most efficient anticancer drugs over
      the past decade; however, its poor water solubility and systemic toxicity have
      greatly limited its clinical application. In recent decades, the emergence of
      nanotechnology has provided new drug delivery systems for docetaxel, which can
      improve its water solubility, minimize the side effects and increase the tumor
      targeting distribution by passive or active targeting. This review focuses on the
      research progress in nanoformulations related to docetaxel delivery - such as
      polymer-based, lipid-based, and lipid-polymer hybrid nanocarriers, as well as
      inorganic nanoparticles - addressing their structures, characteristics,
      preparation, physicochemical properties, methods by which drugs are loaded into
      them, and their in vitro and in vivo efficacies. Further, the targeted ligands
      used in the docetaxel nanoformulations, such as monoclonal antibodies, peptides,
      folic acid, transferrin, aptamers and hyaluronic acid, are described. The issues
      to overcome before docetaxel nanoformulations can be used in clinical and
      commercial applications are also discussed. 

PMID- 23950646
TI  - Shared decision making in psychiatric practice and the primary care setting is
      unique, as measured using a 9-item Shared Decision Making Questionnaire (SDM-Q
      9).
AB  - BACKGROUND: To measure and compare the extent to which shared a decision making
      (SDM) process is implemented both in psychiatric outpatient clinical encounters
      and in the primary care setting from the patient's perspective. METHODS: A total
      of 1,477 patients recruited from the Canary Islands Health Service mental health
      and primary care departments were invited to complete the nine-item Shared
      Decision Making Questionnaire (SDM-Q-9) immediately after their consultation.
      MANCOVA, Student's t-test, and Pearson correlations were used to assess the
      relationship and differences between SDM-Q-9 scores in patient samples. RESULTS:
      No differences were found in SDM-Q-9 total scores between the two patient
      samples, but there were relevant differences when item by item analysis was
      applied; differences were observed according to the different steps of the SDM
      process. SDM is present to a very limited extent in the routine psychiatric
      setting compared to primary care. Patients' age, education, type of appointment,
      and treatment decision all play a specific role in predicting SDM. CONCLUSION:
      The study provides evidence that SDM is a complex process that needs to be
      analyzed according to its different steps. SDM patterns were different in the
      primary care and psychiatric outpatient care settings and reflect quite a
      different perspective of the decision making process.

PMID- 23950648
TI  - A Case of early onset Parkinson's disease after major stress.
AB  - A 38-year-old woman experienced sudden onset of rest tremor in the left forearm 1
      week after learning that her deeply loved husband was involved in an affair. The
      patient was in good health and had no neurological disease or prior trauma. The
      surface electromyography results were consistent with features of the typical
      rest tremor, and the increased glucose metabolism in the putamen, seen on
      positron emission tomography scan, was consistent with the early stages of
      Parkinson's disease (PD). Furthermore, her trembling symptoms were relieved
      significantly after antiparkinsonian medications. For this patient, stress played
      an important role in the development of PD. The mechanism may have been the
      direct effects of numerous neurotransmitters or dopamine depletion after its
      massive release during severe stress. This case suggests that severe stress can
      worsen the neurological symptoms and prompted early onset of PD. It is the first
      case of PD occurring so early in life after exposure to major stress, and arouses
      our attention to the effects of stress on the nervous system. 

PMID- 23950647
TI  - Self-concept evaluation and migraine without aura in childhood.
AB  - INTRODUCTION: Self-esteem is related to the broadly understood concept of self
      schemas and is a crucial mechanism for a correct psychological development in
      children and adolescents. The impact of the many psychological difficulties
      linked to the migraine without aura (MoA) and recurrent headache attacks, such as
      anger and separation anxiety, on self-esteem has not yet been well investigated.
      The aims of the present study were to assess self-esteem levels in an objective
      way and to verify their possible relationship and correlation with the frequency
      and intensity of migraine attacks, in a population of children and adolescents
      affected by MoA. METHODS: The study population was comprised of 185 children (88
      males [M],97 females [F]) aged between 6 and 12 years (mean 9.04 +/- 2.41 years)
      referred consecutively for MoA to the Center for Childhood Headache, Clinic of
      Child and Adolescent Neuropsychiatry, Second University of Naples and of 203
      healthy controls (95 M, 108 F) with mean age 9.16 +/- 2.37 years, recruited from
      schools in Campania. The monthly headache frequency and the mean headache
      duration were assessed from daily headache diaries kept by all the children, and
      MoA intensity was assessed on a VAS (visual analog scale). To further evaluate
      their level of self-concept, all subjects filled out the Multidimensional Self
      Concept Scale (MSCS). RESULTS: The two study groups were comparable for age (P =
      0.621), sex (P = 0.960), and z-score BMI (P = 0.102). The MoA group showed a
      significant reduction in the MSCS total score (P < 0.001) and in the Social (P <
      0.001), Affect (P < 0.001), Family (P < 0.001), and Physical (P < 0.001) domains
      of the MSCS compared with the control group. The Pearson's correlation analysis
      showed a significantly negative relationship between MoA clinical characteristics
      and MSCS scores, and similarly the frequency of attacks was significantly
      negatively related with the Social (r = -0.3176; P < 0.001), Competence (r = 
      0.2349; P = 0.001), Physical (r = -0.2378; P = 0.001), and total (r = -0.2825; P
      < 0.001) scores of the MSCS. On the other hand, the MoA duration was
      significantly negatively related with the Social (r = -0.1878; P = 0.01),
      Competence (r = -0.2270; P = 0.002), Physical (r = -0.1976; P = 0.007), and total
      (r = -0.1903; P = 0.009) scores of the MSCS. CONCLUSION: Our study first
      identified differences in self-esteem levels, with an objective tool, in children
      affected by MoA compared with controls, suggesting the need for evaluation of
      self-esteem for better psychological pediatric management of children with
      migraine.

PMID- 23950649
TI  - Intermittent hypoxia from obstructive sleep apnea may cause neuronal impairment
      and dysfunction in central nervous system: the potential roles played by
      microglia.
AB  - Obstructive sleep apnea (OSA) is a common condition characterized by repetitive
      episodes of complete (apnea) or partial (hypopnea) obstruction of the upper
      airway during sleep, resulting in oxygen desaturation and arousal from sleep.
      Intermittent hypoxia (IH) resulting from OSA may cause structural neuron damage
      and dysfunction in the central nervous system (CNS). Clinically, it manifests as
      neurocognitive and behavioral deficits with oxidative stress and inflammatory
      impairment as its pathophysiological basis, which are mediated by microglia at
      the cellular level. Microglia are dominant proinflammatory cells in the CNS. They
      induce CNS oxidative stress and inflammation, mainly through mitochondria,
      reduced nicotinamide adenine dinucleotide phosphate oxidase, and the release of
      excitatory toxic neurotransmitters. The balance between neurotoxic versus
      protective and anti- versus proinflammatory microglial factors might determine
      the final roles of microglia after IH exposure from OSA. Microglia inflammatory
      impairments will continue and cascade persistently upon activation, ultimately
      resulting in clinically significant neuron damage and dysfunction in the CNS. In
      this review article, we summarize the mechanisms of structural neuron damage in
      the CNS and its concomitant dysfunction due to IH from OSA, and the potential
      roles played by microglia in this process. 

PMID- 23950650
TI  - Clinical features and imaging findings in a case of Capgras syndrome.
AB  - Capgras syndrome consists of the delusional belief that a person or persons have
      been replaced by doubles or impostors. It can occur in the context of both
      psychiatric and organic illness, and seems to be related to lesions of the
      bifrontal and right limbic and temporal regions. Indeed, magnetic resonance
      imaging has revealed brain lesions in patients suffering from Capgras syndrome.
      This case study reports the findings of a thorough diagnostic evaluation in a
      woman suffering from Capgras syndrome and presenting with the following clinical
      peculiarities: obsessive modality of presentation of the delusional ideation,
      intrusiveness of such ideation (that even disturbed her sleep), as well as a
      sense of alienation and utter disgust towards the double. These characteristics
      bring to mind the typical aspects of obsessive-compulsive disorder. Neuroanatomic
      investigation, through magnetic resonance imaging, performed on this patient
      showed alteration of the bilateral semioval centers, which are brain regions
      associated with the emotion of disgust and often show alterations in subjects
      suffering from obsessive-compulsive disorder. Hence, neuroimaging allows
      researchers to put forward the hypothesis of a common neuroanatomic basis for
      Capgras syndrome and obsessive-compulsive disorder, at least for cases in which
      the delusional ideation is associated with deep feelings of disgust and presents
      with a certain pervasiveness. 

PMID- 23950651
TI  - Tobacco smoking in treatment-resistant schizophrenia patients is associated with
      impaired cognitive functioning, more severe negative symptoms, and poorer social
      adjustment.
AB  - Tobacco smoking is common in schizophrenia patients. It has been reported that
      schizophrenia patients who are tobacco smokers have better cognitive performances
      compared to those who are nonsmokers. However, little is known on the effects of
      tobacco smoking in treatment-resistant schizophrenia (TRS) patients. The aim of
      this study was to compare cognitive performances, psychotic symptoms, and social
      adjustment in tobacco smoker TRS patients compared to nonsmoker TRS patients.
      Smoker and nonsmoker TRS patients did not differ in demographics and in mean
      daily antipsychotic dose. Smoker TRS patients had significantly higher scores
      than nonsmoker patients on the positive and negative syndrome scale (PANSS) and
      on the negative symptoms subscale. These patients also performed worse than
      nonsmoker patients on problem-solving cognitive domain. Social adjustment was not
      significantly different between the two groups. In both groups of patients, worse
      cognitive performances were mostly predicted by higher severity of negative
      symptoms. Worse performances on the verbal memory and problem-solving cognitive
      domains were correlated with social-functioning impairment in tobacco smoker TRS
      patients but not in nonsmoker ones. The results showed that tobacco smoking was
      not significantly associated with better cognitive performances in TRS patients,
      while it was significantly associated with higher negative symptoms. Even if a
      direct causative mechanism cannot be inferred and despite the fact that these
      patients may use tobacco to self-medicate, it could be speculated that these
      associations may, at least partially, be related to a tobacco-smoking-induced
      worsening of abnormal dopamine dysfunction, which has been suggested to occur in
      TRS patients. 

PMID- 23950652
TI  - Activation of the sonic hedgehog signaling pathway occurs in the CD133 positive
      cells of mouse liver cancer Hepa 1-6 cells.
AB  - BACKGROUND: The important role of cancer stem cells in carcinogenesis has been
      emphasized in research. CD133+ cells have been mentioned as liver cancer stem
      cells in hepatocellular carcinoma (HCC). Some researchers have proposed that the
      sonic hedgehog (Shh) pathway contributes to hepatocarcinogenesis and that the
      pathway activation occurs mainly in cancer stem cells. We investigated whether
      the activation of the Shh pathway occurs in CD133+ cells from liver cancer.
      MATERIALS AND METHODS: We used magnetic sorting to isolate CD133+ cells from
      mouse cancer Hepa 1-6 cells. To examine the clonogenicity, cell culture and soft
      agar colony formation assay were performed between CD133+ and CD133- cells. To
      study the activation of the Shh pathway, we examined the mRNA expressions of Shh,
      patched homolog 1 (Ptch-1), glioma-associated oncogene homolog 1 (Gli-1), and
      smoothened homolog (Smoh) by real-time polymerase chain reaction of both CD133+
      and CD133- cells. RESULTS: The number (mean +/- standard deviation) of colonies
      of CD133+ cells and CD133- cells was 1,031.0 +/- 104.7 and 119.7 +/- 17.6
      respectively. This difference was statistically significant (P < 0.001). Their
      clonogenicity was 13.7% +/- 1.4% and 1.6% +/- 0.2% respectively with a
      statistically significant difference found (P < 0.001). CD133+ cells and CD133-
      cells were found to have statistically significant differences in Shh mRNA and
      Smoh mRNA (P = 0.005 and P = 0.043 respectively). CONCLUSION: CD133+ Hepa 1-6
      cells have a significantly higher colony proliferation and clonogenicity. The Shh
      pathway is activated in these cells that harbor stem cell features, with an
      underexpression of Shh mRNA and an overexpression of Smoh mRNA. Blockade of the
      Shh signaling pathway may be a potential therapeutic strategy for
      hepatocarcinogenesis.

PMID- 23950653
TI  - 454 next generation-sequencing outperforms allele-specific PCR, Sanger
      sequencing, and pyrosequencing for routine KRAS mutation analysis of formalin
      fixed, paraffin-embedded samples.
AB  - Detection of KRAS mutations in archival pathology samples is critical for
      therapeutic appropriateness of anti-EGFR monoclonal antibodies in colorectal
      cancer. We compared the sensitivity, specificity, and accuracy of Sanger
      sequencing, ARMS-Scorpion (TheraScreen(r)) real-time polymerase chain reaction
      (PCR), pyrosequencing, chip array hybridization, and 454 next-generation
      sequencing to assess KRAS codon 12 and 13 mutations in 60 nonconsecutive selected
      cases of colorectal cancer. Twenty of the 60 cases were detected as wild-type
      KRAS by all methods with 100% specificity. Among the 40 mutated cases, 13 were
      discrepant with at least one method. The sensitivity was 85%, 90%, 93%, and 92%,
      and the accuracy was 90%, 93%, 95%, and 95% for Sanger sequencing, TheraScreen
      real-time PCR, pyrosequencing, and chip array hybridization, respectively. The
      main limitation of Sanger sequencing was its low analytical sensitivity, whereas
      TheraScreen real-time PCR, pyrosequencing, and chip array hybridization showed
      higher sensitivity but suffered from the limitations of predesigned assays.
      Concordance between the methods was k = 0.79 for Sanger sequencing and k > 0.85
      for the other techniques. Tumor cell enrichment correlated significantly with the
      abundance of KRAS-mutated deoxyribonucleic acid (DNA), evaluated as DeltaCt for
      TheraScreen real-time PCR (P = 0.03), percentage of mutation for pyrosequencing
      (P = 0.001), ratio for chip array hybridization (P = 0.003), and percentage of
      mutation for 454 next-generation sequencing (P = 0.004). Also, 454 next
      generation sequencing showed the best cross correlation for quantification of
      mutation abundance compared with all the other methods (P < 0.001). Our
      comparison showed the superiority of next-generation sequencing over the other
      techniques in terms of sensitivity and specificity. Next-generation sequencing
      will replace Sanger sequencing as the reference technique for diagnostic
      detection of KRAS mutation in archival tumor tissues. 

PMID- 23950654
TI  - Human epidermal growth factor receptor-2 overexpression and amplification in
      metastatic and recurrent high grade or type 2 endometrial carcinomas.
AB  - INTRODUCTION: Human epidermal growth factor receptor (HER)-2 overexpression or
      gene amplification is more common in high-grade or type 2 endometrial carcinomas.
      We assessed the discordance of HER-2 expression between primary and metastatic or
      recurrent endometrial carcinomas. MATERIALS AND METHODS: Thirty-six primary,
      along with 14 metastatic and five recurrent tumors (matched to primaries),
      pathologically confirmed as high-grade or type 2 endometrial carcinomas, were
      submitted for immunohistochemistry (IHC) for HER-2. Fluorescence in situ
      hybridization was performed when the tumors showed HER-2 overexpression (>=2+ IHC
      score). The results of the IHC and fluorescence in situ hybridization assays were
      compared between the primary and metastatic or recurrent tumors. The
      relationships between HER-2 expression and clinicopathological factors or
      prognosis were investigated. RESULTS: HER-2 overexpression and HER-2
      amplification (a ratio of HER-2 copies to chromosome 17 [CEP17] copies >=2.2)
      were detected in 33.3% (twelve of 36 patients) and 5.6% (two of 36 patients) of
      primary tumors, respectively. HER-2 overexpression was not associated with
      clinicopathological factors or prognosis. In 19 tumor specimens obtained from
      metastatic or recurrent tumors, HER-2 overexpression and HER-2 amplification were
      detected in 57.9% (eleven patients) and 15.8% (three patients), respectively. HER
      2 overexpression tended to predict a worse prognosis. CONCLUSION: HER-2
      expression in metastatic or recurrent tumors was more frequent than in matched
      primary high-grade or type 2 endometrial carcinomas. Trastuzumab in combination
      with cytotoxic chemotherapy may represent an alternative therapeutic option for
      these tumors.

PMID- 23950655
TI  - Platelet aggregation measurement for assessment of hemostasis failure mechanisms
      in patients with gastroduodenal ulcer bleeding.
AB  - BACKGROUND: The purpose of this study was to identify factors associated with the
      risk of unsustainable hemostasis in patients with gastric and duodenal ulcer
      bleeding by in vitro assessment of platelet reactivity using artificial neural
      networks. METHODS: Patients with gastroduodenal ulcers complicated by bleeding
      were studied. Platelet aggregation was measured using aggregometry with adenosine
      diphosphate 5 MUM, epinephrine 2.5 MUM, 5-hydroxytryptophan 10 MUM, collagen 1
      MUM, and thrombin 0.06 NIH Unit/mL as agonists. Multiple logistic regression was
      used to evaluate the independent relationship between demographic, clinical,
      endoscopic, and laboratory data and in vitro assessment of platelet reactivity
      and local parameters of hemostasis in patients with ulcer bleeding. RESULTS:
      Analysis of platelet aggregation in patients with gastroduodenal ulcer bleeding
      allowed the variability of platelet response to different agonists used in
      effective concentration which induces 50% platelet aggregation (EC50) to be
      established. The relationship between platelet aggregation and the spatial
      temporal characteristics of ulcers complicated by bleeding was demonstrated.
      Adrenoreactivity of platelets was associated with time elapsed since the start of
      ulcer bleeding and degree of hemorrhage. The lowest platelet response to collagen
      and thrombin was detected in patients with active bleeding (P < 0.001) and
      unsustainable recent bleeding (P < 0.01). Decreased adenosine diphosphate-induced
      platelet aggregation in patients with ulcer bleeding was correlated with the
      platelet response to thrombin (r = 0.714, P < 0.001) and collagen (r = 0.584, P <
      0.01). CONCLUSION: Estimation of platelet reactivity in vitro indicates the key
      mechanisms of failure of hemostasis in patients with ulcer bleeding. In addition
      to gender, an important determinant of unsustainable hemostasis was a decreased
      platelet response to thrombin and adenosine diphosphate.

PMID- 23950656
TI  - Controlled progressive innate immune stimulation regimen prevents the induction
      of sickness behavior in the open field test.
AB  - Peripheral immune activation by bacterial mimics or live replicating pathogens is
      well known to induce central nervous system activation. Sickness behavior
      alterations are often associated with inflammation-induced increases in
      peripheral proinflammatory cytokines (eg, interleukin [IL]-1beta and IL-6).
      However, most researchers have used acute high dose endotoxin/bacterial
      challenges to observe these outcomes. Using this methodology may pose inherent
      risks in the translational interpretation of the experimental data in these
      studies. Studies using Escherichia coli have yet to establish the full kinetics
      of repeated E. coli peripheral injections. Therefore, we sought to examine the
      effects of repeated low dose E. coli on sickness behavior and local peripheral
      inflammation in the open field test. Results from the current experiments showed
      a behavioral dose response, where increased amounts of E. coli resulted in
      correspondingly increased sickness behavior. Furthermore, animals that received a
      subthreshold dose (ie, one that did not cause sickness behavior) of E. coli 24
      hours prior were able to withstand a larger dose of E. coli on the second day (a
      dose that would normally cause sickness behavior in mice without prior exposure)
      without inducing sickness behavior. In addition, animals that received escalating
      subthreshold doses of E. coli on days 1 and 2 behaviorally tolerated a dose of E.
      coli 25 times higher than what would normally cause sickness behavior if given
      acutely. Lastly, increased levels of E. coli caused increased IL-6 and IL-1beta
      protein expression in the peritoneal cavity, and this increase was blocked by
      administering a subthreshold dose of E. coli 24 hours prior. These data show that
      progressive challenges with subthreshold levels of E. coli may obviate the
      induction of sickness behavior and proinflammatory cytokine expression. 

PMID- 23950657
TI  - Potential role of gabapentin and extended-release gabapentin in the management of
      menopausal hot flashes.
AB  - About 80% of postmenopausal women experience vasomotor symptoms, such as hot
      flashes and night sweats - symptoms that are associated with sleep disruption and
      can lead to fatigue and mood changes. Moreover, hot flashes can be embarrassing
      for women, causing difficulties at work and in their social lives. Many therapies
      have been advocated for relief of vasomotor symptoms, but only hormone therapy
      has been US Food and Drug Administration approved. However, after the Women's
      Health Initiative Study suggested that there was a correlation between hormone
      therapy and increased risk for breast cancer and cardiovascular events, many
      women stopped taking hormone therapy, and many do not want to initiate it.
      Hormone therapy is also contraindicated in certain women, such as those with a
      history of hormone-stimulated cancer like breast and uterine cancer. Gabapentin
      (Neurontin) has shown efficacy in relieving vasomotor symptoms and is used as off
      label for this indication. A new extended-release formulation of gabapentin has
      also shown efficacy in treating hot flashes and improving sleep quality with
      possibly fewer side effects than regular gabapentin. 

PMID- 23950658
TI  - Cost-effectiveness of an aprepitant regimen for prevention of chemotherapy
      induced nausea and vomiting in patients with breast cancer in the UK.
AB  - PURPOSE: Prevention of chemotherapy-induced nausea and vomiting (CINV) remains an
      important goal for patients receiving chemotherapy. The objective of this study
      was to define, from the UK payer perspective, the cost-effectiveness of an
      antiemetic regimen using aprepitant, a selective neurokinin-1 receptor
      antagonist, for patients receiving chemotherapy for breast cancer. METHODS: A
      decision-analytic model was developed to compare an aprepitant regimen
      (aprepitant, ondansetron, and dexamethasone) with a standard UK antiemetic
      regimen (ondansetron, dexamethasone, and metoclopramide) for expected costs and
      health outcomes after single-day adjuvant chemotherapy for breast cancer. The
      model was populated with results from patients with breast cancer participating
      in a randomized trial of CINV preventative therapy for cycle 1 of single-day
      chemotherapy. RESULTS: During 5 days after chemotherapy, 64% of patients
      receiving the aprepitant regimen and 47% of those receiving the UK comparator
      regimen had a complete response to antiemetic therapy (no emesis and no rescue
      antiemetic therapy). A mean of L37.11 (78%) of the cost of aprepitant was offset
      by reduced health care resource utilization costs. The predicted gain in quality
      adjusted lifeyears (QALYs) with the aprepitant regimen was 0.0048. The
      incremental cost effectiveness ratio (ICER) with aprepitant, relative to the UK
      comparator, was L10,847/QALY, which is well below the threshold commonly accepted
      in the UK of L20,000-L30,000/QALY. CONCLUSION: The results of this study suggest
      that aprepitant is cost-effective for preventing CINV associated with
      chemotherapy for patients with breast cancer in the UK health care setting.

PMID- 23950659
TI  - Rotavirus gastroenteritis in children under 5 years in the Kingdom of Bahrain:
      hospital-based surveillance.
AB  - PURPOSE: Rotavirus (RV) is the leading cause of morbidity and mortality in
      children under 5 years of age worldwide. This study assessed the role of RV as a
      cause of gastroenteritis (GE)-associated hospitalization in children, generating
      baseline information to evaluate the potential impact of the RV vaccine in
      reducing RVGE disease burden in the Kingdom of Bahrain. METHODS: This single,
      pediatric hospital-based surveillance study was conducted over a period of 12
      months beginning April 1, 2006. A total of 314 children aged under 5 years and
      hospitalized due to GE were enrolled in the study, following collection of
      written informed consent from parents/guardians. Stool samples were tested for
      the presence of RV using enzyme immunoassay, and a random subset of RV-positive
      samples was further genotyped using reverse transcriptase-polymerase chain
      reaction and reverse hybridization assay. RESULTS: Of 314 enrolled children, 239
      were included in the final analysis. RV was detected in 107 children (44.8%),
      mostly in the 6-23 months age group (82/107; 76.6%). RVGE occurred throughout the
      year, with the highest proportion occurring during April (26/42; 61.9%). G1P[8[
      was the most commonly detected RV strain (10/17; 58.8%) in the limited number of
      samples analyzed. Vomiting and severe RVGE were more commonly observed in RV
      positive than RV-negative children before hospitalization (P = 0.0008 and 0.0204,
      respectively). CONCLUSION: In our study, RV accounted for over 40% of GE
      associated hospitalizations and particularly affected children under 2 years of
      age. These data will serve as a baseline for assessing the potential changes in
      the epidemiology of RV disease and for evaluating the potential impact of the
      introduction of RV vaccination.

PMID- 23950660
TI  - Use of existing data sources in clinical epidemiology: Finnish health care
      registers in Alzheimer's disease research - the Medication use among persons with
      Alzheimer's disease (MEDALZ-2005) study.
AB  - Memory diseases are the most important determinant of health care service use and
      quality of life among older individuals. Adverse effects of medication are common
      among older people, but this age group is underrepresented in clinical trials.
      Finnish statutory health care and prescription registers, together with personal
      identification numbers (PINs) and a tax-supported public health plan covering all
      citizens provide excellent opportunities for epidemiological research. We used
      routinely collected data from the Finnish health care system to establish the
      Medication use among persons with Alzheimer's disease (MedAlz-2005) cohort. This
      cohort study will be used to assess medication use and its effects on health
      status and hospitalization among persons with Alzheimer's disease (Ad). The
      cohort includes all community-dwelling persons who had a clinically verified
      diagnosis of Ad, resided in Finland, and were alive on December 31, 2005 and a
      matched comparison person for each affected individual. data on purchased
      prescription medicines (1995-2009), inpatient hospital admissions (1972-2009),
      outpatient visits (1995-2009), details on diagnosed cancers (1972-2009), and
      mortality (until October 2010) are available for the whole cohort. This paper
      describes how this data can be utilized in etiological research and the
      assessment of health care service use, drug utilization, and associated adverse
      outcomes in a particularly vulnerable group that is often underrepresented in
      clinical trials. 

PMID- 23950662
TI  - Maternal mortality in rural South Africa: the impact of case definition on levels
      and trends.
AB  - BACKGROUND: Uncertainty in the levels of global maternal mortality reflects data
      deficiencies, as well as differences in methods and definitions. This study
      presents levels and trends in maternal mortality in Agincourt, a rural
      subdistrict of South Africa, under long-term health and sociodemographic
      surveillance. METHODS: All deaths of women aged 15 years-49 years occurring in
      the study area between 1992 and 2010 were investigated, and causes of death were
      assessed by verbal autopsy. Two case definitions were used: "obstetrical"
      (direct) causes, defined as deaths caused by conditions listed under O00-O95 in
      International Classification of Diseases-10; and "pregnancy-related deaths",
      defined as any death occurring during the maternal risk period (pregnancy,
      delivery, 6 weeks postpartum), irrespective of cause. RESULTS: The case
      definition had a major impact on levels and trends in maternal mortality. The
      obstetric mortality ratio averaged 185 per 100,000 live births over the period
      (60 deaths), whereas the pregnancy-related mortality ratio averaged 423 per
      100,000 live births (137 deaths). Results from both calculations increased over
      the period, with a peak around 2006, followed by a decline coincident with the
      national roll-out of Prevention of Mother-to-Child Transmission of HIV and
      antiretroviral treatment programs. Mortality increase from direct causes was
      mainly due to hypertension or sepsis. Mortality increase from other causes was
      primarily due to the rise in deaths from HIV/AIDS and pulmonary tuberculosis.
      CONCLUSION: These trends underline the major fluctuations induced by emerging
      infectious diseases in South Africa, a country undergoing rapid and complex
      health transitions. Findings also pose questions about the most appropriate case
      definition for maternal mortality and emphasize the need for a consistent
      definition in order to better monitor and compare trends over time and across
      settings.

PMID- 23950664
TI  - Rapid recovery following fulminant meningococcemia complicated by myocarditis in
      a 15-year-old Nepalese girl: a case report.
AB  - INTRODUCTION: Fulminant meningococcemia is a relatively rare life-threatening
      disease caused by Neisseria meningitidis. The clinical presentation is varied,
      but, when associated with myocarditis, it carries a particularly poor prognosis.
      We report a case of a patient with fulminant meningococcemia who subsequently
      developed severe myocardial dysfunction and successfully recovered within a
      period of 14 days of hospitalization. CASE PRESENTATION: A 15-year-old girl
      presented with headache, fever, body ache, and diarrhea for 1 day, and ecchymotic
      rash over her body for 4 hours. Blood cultures confirmed infection with N.
      meningitidis. After 6 days in the hospital, the patient developed anasarca,
      elevated jugular venous pressure, and shock. The patient was managed with
      intravenous ceftriaxone and captopril. Over the next 3 days the patient rapidly
      improved and started walking. CONCLUSION: Meningococcemia complicated by
      myocarditis has an extremely poor prognosis with high mortality. Our case
      suggests that recovery from a severe myocardial dysfunction can occur rapidly
      within a few days. Prompt recognition and management in this case might have
      contributed to the patient's rapid recovery from myocarditis.

PMID- 23950663
TI  - Treatment of symptomatic uterine fibroids with green tea extract: a pilot
      randomized controlled clinical study.
AB  - BACKGROUND: Uterine fibroids (UFs, also known as leiomyoma) affect 70% of
      reproductive-age women. Imposing a major burden on health-related quality-of-life
      (HRQL) of premenopausal women, UF is a public health concern. There are no
      effective medicinal treatment options currently available for women with
      symptomatic UF. OBJECTIVES: To evaluate the efficacy and safety of green tea
      extract (epigallocatechin gallate [EGCG]) on UF burden and quality of life in
      women with symptomatic UF, in a double-blinded, placebo-controlled randomized
      clinical trial. METHODS: A total of 39 reproductive-age women (age 18-50 years,
      day 3 serum follicle-stimulating hormone <10 ?U/mL) with symptomatic UF were
      recruited for this study. All subjects had at least one fibroid lesion 2 cm(3) or
      larger, as confirmed by transvaginal ultrasonography. The subjects were
      randomized to oral daily treatment with either 800 mg of green tea extract (45%
      EGCG) or placebo (800 mg of brown rice) for 4 months, and UF volumes were
      measured at the end, also by transvaginal ultrasonography. The fibroid-specific
      symptom severity and HRQL of these UF patients were scored at each monthly visit,
      using the symptom severity and quality-of-life questionnaires. Student's t-test
      was used to evaluate statistical significance of treatment effect between the two
      groups. RESULTS: Of the final 39 women recruited for the study, 33 were compliant
      and completed all five visits of the study. In the placebo group (n = 11),
      fibroid volume increased (24.3%) over the study period; however, patients
      randomized to green tea extract (n = 22, 800 mg/day) treatment showed significant
      reduction (32.6%, P = 0.0001) in total UF volume. In addition, EGCG treatment
      significantly reduced fibroid-specific symptom severity (32.4%, P = 0.0001) and
      induced significant improvement in HRQL (18.53%, P = 0.01) compared to the
      placebo group. Anemia also significantly improved by 0.7 g/dL (P = 0.02) in the
      EGCG treatment group, while average blood loss significantly decreased from 71
      mL/month to 45 mL/month (P = 0.001). No adverse effects, endometrial hyperplasia,
      or other endometrial pathology were observed in either group. CONCLUSION: EGCG
      shows promise as a safe and effective therapeutic agent for women with
      symptomatic UFs. Such a simple, inexpensive, and orally administered therapy can
      improve women's health globally.

PMID- 23950665
TI  - Individual psychotherapy for schizophrenia: trends and developments in the wake
      of the recovery movement.
AB  - Although the role and relative prominence of psychotherapy in the treatment of
      schizophrenia has fluctuated over time, an analysis of the history of
      psychotherapy for schizophrenia, focusing on findings from the recovery movement,
      reveals recent trends including the emergence of the development of integrative
      psychotherapy approaches. The authors suggest that the recovery movement has
      revealed limitations in traditional approaches to psychotherapy, and has provided
      opportunities for integrative approaches to emerge as a mechanism for promoting
      recovery in persons with schizophrenia. Five approaches to integrative
      psychotherapy for persons with schizophrenia are presented, and a shared
      conceptual framework that allows these five approaches to be compatible with one
      another is proposed. The conceptual framework is consistent with theories of
      recovery and emphasizes interpersonal attachment, personal narrative, and
      metacognitive processes. Implications for future research on integrative
      psychotherapy are considered. 

PMID- 23950666
TI  - Anemia management: development of a rapidaccess anemia and intravenous iron
      service.
AB  - This article describes the initiation and evolution of the Rapid-Access Anemia
      Clinic (RAAC) at Guy's and St Thomas' Hospitals, London, UK. This clinic was set
      up to provide diagnosis and treatment, and to coordinate investigative
      procedures, where necessary, into the underlying causes of anemia. Initially
      piloted with anemic preoperative orthopedic patients, the clinic now treats a
      wide range of conditions, deriving from both internal and external referrals.
      Treatment includes dietary advice, supplementation with iron, vitamin B12 and
      folate, and blood transfusion. Most patients at the RAAC need iron replacement,
      the majority of which require intravenous (IV) iron. Therefore the first-line IV
      iron-administration protocol is carefully considered to ensure viability of the
      service and patient satisfaction. Four IV irons available in the UK are
      discussed, with explanation of the benefits and drawbacks of each product and the
      reasoning behind the IV iron choice at different stages of the RAAC's
      development. Costs to the service, affected by IV iron price and administration
      regimen, are considered, as well as the product's contraindications. Finally, the
      authors reflect on the success of the RAAC and how it has improved patients'
      quality-of-treatment experience, in addition to benefiting the hospital and
      National Health Service in achieving specific health-care mandates and
      directives. Drawing from the authors' experiences, recommendations are given to
      assist others in setting up and providing a successful rapid-access anemia
      service or similar facility. 

PMID- 23950667
TI  - The genus Alterosa Blahnik, 2005 (Trichoptera, Philopotamidae, Philopotaminae) in
      northeastern Brazil, including the description of three new species and an
      identification key for the genus.
AB  - Alterosa Blahnik, 2005 contains 35 described species distributed in southern and
      southeastern Brazil. Three new species of Alterosa from northeastern Brazil are
      described and illustrated, Alterosa amadoi sp. n., Alterosa castroalvesi sp. n.
      and Alterosa caymmii sp. n., the first records of the genus from northeastern
      Brazil. An identification key for all known species of the genus is also
      presented. 

PMID- 23950668
TI  - Anagnorisma chamrani sp. n. (Lepidoptera, Noctuidae) from Iran.
AB  - A new Anagnorisma species, Anagnorisma chamrani sp. n., is described from
      Binaloud Mountains of Khorasan-e-Razavi province in north-eastern Iran, and
      compared with its sister species, Anagnorisma eucratides (Boursin, 1960). The
      adults, and male and female genitalia of both species are illustrated in 11
      figures. The genus Anagnorisma is recorded for the first time for the fauna of
      Iran. 

PMID- 23950669
TI  - An illustrated key to the genera of Thripinae (Thysanoptera, Thripidae) from
      Iran.
AB  - An illustrated key is provided for the identification of 35 genera of Thripinae
      (Thysanoptera: Thripidae) from Iran with comments for each genus. Chirothrips
      maximi Ananthakrishnan and Limothrips cerealium Haliday are recorded from Iran
      for the first time. A checklist is provided of Thripinae recorded from this
      country. 

PMID- 23950670
TI  - New data on the genus Derops Sharp (Coleoptera, Staphylinidae, Tachyporinae) from
      China with description of two new species.
AB  - Two new Chinese species of Derops are described: Derops hainanus sp. n. from
      Hainan and Derops yunnanus sp. n. from Yunnan. Females of Derops punctipennis
      Schulke and Derops schillhammeri Schulke are described for the first time and new
      provinces records of Derops smetanai Schulke and Derops dingshanus Watanabe are
      reported. The key to Chinese species of Derops published by Schulke 2003 is
      modified to include the new species. 

PMID- 23950671
TI  - The larva of Drusus vinconi Sipahiler, 1992 (Trichoptera, Limnephilidae,
      Drusinae).
AB  - This paper describes the previously unknown larva of Drusus vinconi Sipahiler,
      1992. Information on the morphology of the 5th larval instar is given, and the
      most important diagnostic features are illustrated. In the context of existing
      identification keys the larva of Drusus vinconi keys together with Drusus
      annulatus (Stephens, 1837), Drusus biguttatus (Pictet, 1834), Drusus ingridae
      Sipahiler, 1993, Hadimina torosensis Sipahiler, 2002 and Leptodrusus budtzi
      (Ulmer, 1913). These species differ in the contours of the pronotum in lateral
      view, the presence/absence of the pronotal transverse groove, the shape of the
      median notch of the pronotum (in anterior view), pronotal sculpturing,
      presence/absence of the lateral carina of the head capsule, the number of proximo
      dorsal setae on the mid-and hind femora, where the lateral fringe starts on the
      abdomen, and in geographic distribution. With respect to zoogeography, Drusus
      vinconi is a (micro-)endemic of the Western Pyrenees. The species prefers stony
      substratum in springs and springbrooks of the montane and subalpine region (Graf
      et al. 2008; Sipahiler 1992, 1993). As a grazer, the larvae of Drusus vinconi
      feed on biofilm and epilithic algae. 

PMID- 23950672
TI  - A new species of Scelidopetalon Delkeskamp (Coleoptera, Erotylidae) from China
      with a key to world species of the genus.
AB  - A new species Scelidopetalon biwenxuani sp. n. is described from China,
      representing the first occurrence of the genus in Hainan province. A key to the
      world species of this genus is provided. 

PMID- 23950673
TI  - Types of species of Apionidae (Coleoptera) described by Carl Peter Thunberg (1743
      1828) with description of a new genus.
AB  - The type specimens of species of Apionidae described by Carl Peter Thunberg are
      reviewed and lecto- and paralectotypes are designated for Apion craccae Thunberg,
      1813, Apion limbatum Thunberg, 1813, Apion punctigerum Thunberg, 1815 and Apion
      astragali Thunberg, 1815. A new genus Thunbergapion (type species Apion limbatum
      Thunberg, 1813) is described, figured and placed in the tribe Aplemonini
      Kissinger, 1968. The new combination Thunbergapion limbatum (Thunberg, 1813) is
      proposed. A key to the known South African genera of the tribe is given. The
      following new synonymies are established: Oxystoma craccae (Linnaeus, 1767) =
      Apion craccae Thunberg, 1813 syn. n., Ischnopterapion (Ischnopterapion) loti
      (Kirby, 1808) = Apion punctigerum Thunberg, 1815, syn. n., and Pseudoprotapion
      astragali (Paykull, 1800) = Apion astragali Thunberg, 1815, syn. n. 

PMID- 23950674
TI  - The genus Aphidura (Hemiptera, Aphididae) in the collection of the Museum
      national d'Histoire naturelle of Paris, with six new species.
AB  - Specimens were studied of 65 samples of the genus Aphidura (Aphididae, Aphidinae,
      Macrosiphini) from the collection of the Museum national d'Histoire naturelle
      (Paris). The possible synonymies of three pairs of species are discussed. New
      aphid host plant relationships are reported for Aphidura bozhkoae, Aphidura
      delmasi, Aphidura ornata, Aphidura pannonica and Aphidura picta; this last
      species is recorded for first time from Afghanistan. The record of Aphidura
      pujoli from Pakistan is refuted. The fundatrices, oviparous females and males of
      Aphidura delmasi are described. Six new species are established: Aphidura gallica
      sp. n. and Aphidura amphorosiphon sp. n. from specimens caught on species of
      Silene (Caryophyllaceae) from France and Iran, respectively, Aphidura
      pakistanensis sp. n., Aphidura graeca sp. n. and Aphidura urmiensis sp. n. from
      specimens caught on species of Dianthus, Gypsophila and Spergula
      (Caryophyllaceae) from Pakistan, Greece and Iran, respectively, and Aphidura
      iranensis sp. n. from specimens caught on Prunus sp. from Iran. Modifications are
      made to the keys by Blackman and Eastop to aphids living on Dianthus, Gypsophyla,
      Silene, Spergula and Prinsepia and Prunus (Rosaceae). An identification key to
      apterous viviparous females of species of Aphidura is also provided. 

PMID- 23950675
TI  - Nuurcala obesa sp. n. (Blattida, Caloblattinidae) from the Lower Cretaceous
      Yixian Formation in Liaoning Province, China.
AB  - Nuurcala obesa sp. n., in the cockroach family Caloblattinidae, is described from
      the Lower Cretaceous Yixian Formation (Liaoning Province, China) based on a
      combination of differential characters of fore- and hind wing venation,
      colouration and body structures. Systematically, Nuurcala (Vrsansky, 2003), known
      from the Cretaceous sediments of Bon Tsagaan and Khurilt, Mongolia, is closely
      related to other genera of Caloblattinidae known from the Jurassic and Cretaceous
      localities in other parts of Asia. 

PMID- 23950677
TI  - Echinophyllia tarae sp. n. (Cnidaria, Anthozoa, Scleractinia), a new reef coral
      species from the Gambier Islands, French Polynesia.
AB  - A new shallow water scleractinian coral species, Echinophyllia tarae sp. n., is
      described from the Gambier Islands, French Polynesia. It is characterized by an
      encrusting corallum, a few large and highly variable corallites with protruding
      walls, and distinctive costosepta. This coral was observed in muddy environments
      where several colonies showed partial mortality and re-growth. The new species
      has morphological affinities with both Echinophyllia echinata and with
      Echinomorpha nishihirai, from which it can be distinguished on the basis of the
      diameter and the protrusion of the largest corallite, the thickness of the septa,
      and the development of the size of the crown of paliform lobes. 

PMID- 23950676
TI  - Oribatid mites (Acari, Oribatida) from riverine environments of some islands in
      Oceania.
AB  - A checklist of identified oribatid mite taxa from riverine freshwater
      environments from six islands in Polynesia (New Caledonia, Tahiti, Moorea,
      Rurutu, Tubuai, Raiatea) is presented; 18 species, 16 genera and eight families
      were recorded. Trhypochthoniellus longisetus (Berlese, 1904) and Trimalaconothrus
      albulus Hammer, 1972 prevailed on distribution. Fortuynia smiti sp. n.
      (Fortuyniidae) is described from New Caledonia. The new speciesis morphologically
      most similar to Fortuynia marina Hammen, 1960 from New Guinea, but it differs
      from the latter by the longer notogastral setae dm, lm, c 2, p 1, epimeral setae
      3b and adanal setae ad 1 and the presence of prodorsal lateral ridges. 

PMID- 23950678
TI  - Two new species of the bamboo-feeding leafhopper genus Abrus Dai & Zhang
      (Hemiptera, Cicadellidae, Deltocephalinae) from China.
AB  - Two new species of the bamboo-feeding genus Abrus Dai & Zhang, 2002, Abrus
      xishuiensis sp. n. and Abrus langshanensis sp. n., are described and illustrated
      from Guizhou and Hunan, South China. A checklist and a key to 13 known species
      are given. 

PMID- 23950679
TI  - Fossils from the Middle Jurassic of China shed light on morphology of
      Choristopsychidae (Insecta, Mecoptera).
AB  - Choristopsychidae, established by Martynov in 1937 with a single isolated
      forewing, is a little known extinct family in Mecoptera. Since then, no new
      members of this enigmatic family have been described. Based on 23 well-preserved
      specimens with complete body and wings from the Middle Jurassic of northeastern
      China, we report one new genus and three new species of Choristopsychidae, two
      new species of the genus Choristopsyche Martynov, 1937: Choristopsyche perfecta
      sp. n. and Choristopsyche asticta sp. n.; one new species of Paristopsyche gen.
      n.: Paristopsyche angelineae sp. n.; and re-describe Choristopsyche tenuinervis
      Martynov, 1937. In addition, we emend the diagnoses of Choristopsychidae and
      Choristopsyche. Analyzing the forewing length/width ratios of representative
      species in Mecoptera, we confirm that choristopsychids have the lowest ratio of
      forewing length/width, meaning broadest forewings. These findings, the first
      fossil choristopsychids with well-preserved body structure and the first record
      of Choristopsychidae in China, shed light on the morphology of these taxa and
      broaden their distribution from Tajikistan to China, while increasing the
      diversity of Mesozoic Mecoptera in China. 

PMID- 23950680
TI  - Chaetopteryx bucari sp. n., a new species from the Chaetopteryx rugulosa group
      from Croatia (Insecta, Trichoptera, Limnephilidae) with molecular, taxonomic and
      ecological notes on the group.
AB  - We describe a new autumnal caddisfly species Chaetopteryx bucari sp. n. from 8
      localities in the Banovina region of Croatia. We also present molecular,
      taxonomic and ecological notes (emergence, sex ratio and seasonal dynamics) on
      the new species and discuss the distribution of Chaetopteryx species in general
      and the Chaetopteryx rugulosa group in particular. Based on Bayesian phylogenetic
      analysis Chaetopteryx rugulosa schmidi was separated from the clade containing
      the other subspecies of Chaetopteryx rugulosa. Thus the subspecies Chaetopteryx
      rugulosa schmidi is here raised to species level, Chaetopteryx schmidi, as it was
      described originally. We further present distribution data on rare species in the
      genus Chaetopteryx in Croatia. 

PMID- 23950681
TI  - A new Pseudophoxinus (Teleostei, Cyprinidae) species from Southwestern Anatolia,
      with remarks on the distribution of the genus in western Anatolia.
AB  - Pseudophoxinus burduricus sp. n. is described from drainages of Salda and Burdur
      lakes, southwestern Turkey. It is distinguished from other Anatolian
      Pseudophoxinus by a combination of characters: lateral line incomplete, with 21
      39 (commonly 26-37) perforated scales and 47-57+1-2 scales in lateral series;
      101/2-121/2 scale rows between lateral line and dorsal fin origin, 3-4(5) scale
      rows between lateral line and the pelvic fin origin; dorsal fin commonly with
      71/2 branched rays; anal fin commonly with 61/2 branched rays; 7-8(9) gill rakers
      on the first branchial arch; a faint and diffuse epidermal black stripe from eye
      to caudal fin base in alive and preserved individuals; mouth slightly
      subterminal, tip of mouth cleft on about level of lower margin of eye; snout
      rounded, its length greater than eye diameter. Comparison is given with all
      Pseudophoxinus species from western Anatolia. 

PMID- 23950682
TI  - A new species of Polypedilum (Uresipedilum) Oyewo & Saether, 1998 from Zhejiang
      Province of Oriental China (Diptera, Chironomidae).
AB  - A new species of Polypedilum (Uresipedilum) Oyewo & Saether, 1998, Polypedilum
      (Uresipedilum) minimum sp. n. is described as male. A key to adult males of the
      subgenus from China is presented. 

PMID- 23950683
TI  - New species and records of Parametriocnemus Goetghebuer from China (Diptera,
      Chironomidae).
AB  - The Chinese species of Parametriocnemus Goetghebuer are reviewed. Two species,
      Parametriocnemus fortis sp. n. and Parametriocnemus vittatus sp. n. are described
      and illustrated as males, and Parametriocnemus ornaticornis (Kieffer),
      Parametriocnemus scotti (Freeman) and Parametriocnemus brundini Sinharay &
      Chaudhuri are recorded from China for the first time. A key to the males of the
      seven Chinese Parametriocnemus speciesis given. 

PMID- 23950684
TI  - Aroid scarabs in the genus Peltonotus Burmeister (Coleoptera, Scarabaeidae,
      Dynastinae): key to species and new distributional data.
AB  - The southeast Asian scarab beetle genus Peltonotus Burmeister (Scarabaeidae,
      Dynastinae, Cyclocephalini) is reviewed. New country records for Peltonotus morio
      Burmeister (Myanmar and Vietnam), Peltonotus nasutus Arrow (southern China and
      Cambodia), and Peltonotus favonius Jameson and Wada (Myanmar) are reported,
      including a new record in the Palearctic/Sino-Japanese biogeographic region. The
      first female specimen of Peltonotus favonius is described. Biological
      associations with aroid inflorescences are reviewed, and human consumption of
      Peltonotus beetles is reported. A key to all species, paralectotype designations
      for Peltonotus nasutus, diagnoses, and distributions using dynamic mapping tools
      are included. 

PMID- 23950685
TI  - Rediscovery and redescription of the holotype of Liolaemus lemniscatus
      Gravenhorst, 1838 (Reptilia, Squamata, Liolaemidae).
AB  - The presumed lost holotype of Liolaemus lemniscatus Gravenhorst, 1838 has been
      found at the Museum of Natural History of the University of Wroclaw and
      identified by the individual pattern of head scales which matches Gravenhorst's
      drawing. The first detailed description of this specimen is provided. 

PMID- 23950686
TI  - A new species of the genus Ambrostoma Motschulsky (Coleoptera, Chrysomelidae,
      Chrysomelinae) from South Korea, with larval descriptions and biological notes.
AB  - Ambrostoma koreana sp. n. is described from South Korea. Detailed descriptions
      and illustrations of adult and all larval instars are provided and differences to
      closely related species are discussed. Ovoviviparity is reported for the first
      time in the genus Ambrostoma. Notes on distribution, host plant and biology are
      also provided. 

PMID- 23950687
TI  - Description of two new species of the leafhopper subgenus Pediopsoides
      (Pediopsoides) (Hemiptera, Cicadellidae, Macropsinae) from Guangxi Province,
      Southern China.
AB  - Two new species of the Macropsinae leafhopper subgenus Pediopsoides
      (Pediopsoides) Matsumura, 1912, Pediopsoides (Pediopsoides) damingshanensis Li,
      Dai & Li, sp. n. and Pediopsoides (Pediopsoides) tishetshkini Li, Dai & Li sp.
      n., are described and illustrated from Guangxi Province of southern China. A key
      to males is provided to distinguish the species of the subgenus along with a map
      showing the distribution of the new species. 

PMID- 23950688
TI  - A new genus and species of Coenosiini from Costa Rica (Diptera, Muscidae,
      Coenosiinae).
AB  - Palpilongus gen. n. is herein described for one species - Palpilongus bifurcus
      sp. n., from Costa Rica, based on male and females. The striking morphological
      characters of the species - palpus very long, about as long as prementum; upper
      calypter truncate and very short and setae of male sternite 5 bifurcated, confirm
      that this new species is also a new genus in the tribe Coenosiini. Male and
      female terminalia were dissected and illustrated. 

PMID- 23950689
TI  - Ancyronyx Erichson, 1847 (Coleoptera, Elmidae) from Mindoro, Philippines, with
      description of the larvae and two new species using DNA sequences for the
      assignment of the developmental stages.
AB  - Ancyronyx buhid sp. n. and Ancyronyx tamaraw sp. n. are described based on adults
      and larvae, matched using their cox1 or cob DNA sequence data. Additional records
      of Ancyronyx schillhammeri Jach, 1994 and Ancyronyx minerva Freitag & Jach, 2007
      from Mindoro are listed. The previously unknown larva of Ancyronyx schillhammeri
      is also described here, aided by cox1 data. The new species and larval stages are
      described in detail and illustrated by SEM and stacked microscopic images. Keys
      to the adult and larval Ancyronyx species of Mindoro and an updated checklist of
      Philippine Ancyronyx species are provided. The usefulness as bioindicators, the
      phylogenetic relationships and biogeographic aspects affecting the distribution
      patterns are briefly discussed. 

PMID- 23950690
TI  - A review of the New World species of the parasitoid wasp Iconella (Hymenoptera,
      Braconidae, Microgastrinae).
AB  - The New World species of Iconella (Hymenoptera: Braconidae, Microgastrinae) are
      revised. Iconella andydeansi Fernandez-Triana, sp. n., Iconella canadensis
      Fernandez-Triana, sp. n., and Iconella jayjayrodriguezae Fernandez-Triana, sp.
      n., are described as new. Iconella isolata (Muesebeck, 1955), stat. r.,
      previously considered as a subspecies of Iconella etiellae (Viereck, 1911), is
      here elevated to species rank. All species have different, well defined
      geographic distributions and hosts. Taxonomic keys are presented in two formats:
      traditional dichotomous hardcopy versions and links to electronic interactive
      versions (software Lucid 3.5). Numerous illustrations, computer-generated
      descriptions, distributional information, host records (mostly Lepidoptera:
      Crambidae and Pyralidae), and DNA barcodes (where available) are presented for
      every species. Phylogenetic analyses of the barcoding region of COI indicate the
      possibility that Iconella is not monophyletic and that the New World species may
      not form a monophyletic group; more data is needed to resolve this issue. 

PMID- 23950691
TI  - First description of the female of Sinopoda serrata (Wang, 1990) (Araneae,
      Sparassidae).
AB  - The female of Sinopoda serrata (Wang, 1990) is described for the first time from
      Tiantangzhai National Forest Park, Hubei province, China. This species has been
      recorded from the region of Central China. Morphological descriptions and
      illustrations of this species are given. 

PMID- 23950692
TI  - Phonological similarity influences word learning in adults learning Spanish as a
      foreign language.
AB  - Neighborhood density-the number of words that sound similar to a given word (Luce
      & Pisoni, 1998)-influences word-learning in native English speaking children and
      adults (Storkel, 2004; Storkel, Armbruster, & Hogan, 2006): novel words with many
      similar sounding English words (i.e., dense neighborhood) are learned more
      quickly than novel words with few similar sounding English words (i.e., sparse
      neighborhood). The present study examined how neighborhood density influences
      word-learning in native English speaking adults learning Spanish as a foreign
      language. Students in their third-semester of Spanish language classes learned
      advanced Spanish words that sounded similar to many known Spanish words (i.e.,
      dense neighborhood) or sounded similar to few known Spanish words (i.e., sparse
      neighborhood). In three word-learning tasks, performance was better for Spanish
      words with dense rather than sparse neighborhoods. These results suggest that a
      similar mechanism may be used to learn new words in a native and a foreign
      language.

PMID- 23950693
TI  - Factors influencing student perceptions of high-school science laboratory
      environments.
AB  - Science laboratory learning has been lauded for decades for its role in fostering
      positive student attitudes about science and developing students' interest in
      science and ability to use equipment. An expanding body of research has
      demonstrated the significant influence of laboratory environment on student
      learning. Further research has demonstrated differences in student perceptions
      based on giftedness. To explore the relationship between giftedness and students'
      perceptions of their learning environment, we examined students' perceptions of
      their laboratory learning environment in biology courses, including courses
      designated for high-achieving versus regular-achieving students. In addition, to
      explore the relationship between students' perceptions and the extent of their
      experience with laboratory learning in a particular discipline, we examined
      students' perceptions of their laboratory learning environment in first-year
      biology courses versus elective biology courses that require first-year biology
      as a prerequisite. We found that students in high-achieving courses had a more
      favourable perception of all aspects of their learning environment when compared
      with students in regular courses. In addition, student perceptions of their
      laboratory appeared to be influenced by the extent of their experience in
      learning science. Perceptions were consistent amongst regular- and high-achieving
      students regardless of grade level. In addition, perceptions of students in first
      year and beyond were consistent regardless of grade level. These findings have
      critical applications in curriculum development as well as in the classroom.
      Teachers can use student perceptions of their learning environment to emphasize
      critical pedagogical approaches and modify other areas that enable enhancement of
      the science laboratory learning environment.

PMID- 23950694
TI  - Looking into the future of foods and health.
AB  - The health of the population is compromised by poor dietary choices. Resolving
      this situation will require a substantial investment at many levels of science,
      agriculture and food industrialisation. If such investments are undertaken they
      will provide the opportunity to change the food marketplace from a product
      centric, to a consumer centric, strategy competing to deliver health benefits to
      individuals.

PMID- 23950695
TI  - A Model of the Perception of Facial Expressions of Emotion by Humans: Research
      Overview and Perspectives.
AB  - In cognitive science and neuroscience, there have been two leading models
      describing how humans perceive and classify facial expressions of emotion-the
      continuous and the categorical model. The continuous model defines each facial
      expression of emotion as a feature vector in a face space. This model explains,
      for example, how expressions of emotion can be seen at different intensities. In
      contrast, the categorical model consists of C classifiers, each tuned to a
      specific emotion category. This model explains, among other findings, why the
      images in a morphing sequence between a happy and a surprise face are perceived
      as either happy or surprise but not something in between. While the continuous
      model has a more difficult time justifying this latter finding, the categorical
      model is not as good when it comes to explaining how expressions are recognized
      at different intensities or modes. Most importantly, both models have problems
      explaining how one can recognize combinations of emotion categories such as
      happily surprised versus angrily surprised versus surprise. To resolve these
      issues, in the past several years, we have worked on a revised model that
      justifies the results reported in the cognitive science and neuroscience
      literature. This model consists of C distinct continuous spaces. Multiple
      (compound) emotion categories can be recognized by linearly combining these C
      face spaces. The dimensions of these spaces are shown to be mostly configural.
      According to this model, the major task for the classification of facial
      expressions of emotion is precise, detailed detection of facial landmarks rather
      than recognition. We provide an overview of the literature justifying the model,
      show how the resulting model can be employed to build algorithms for the
      recognition of facial expression of emotion, and propose research directions in
      machine learning and computer vision researchers to keep pushing the state of the
      art in these areas. We also discuss how the model can aid in studies of human
      perception, social interactions and disorders.

PMID- 23950696
TI  - Software for computing and annotating genomic ranges.
AB  - We describe Bioconductor infrastructure for representing and computing on
      annotated genomic ranges and integrating genomic data with the statistical
      computing features of R and its extensions. At the core of the infrastructure are
      three packages: IRanges, GenomicRanges, and GenomicFeatures. These packages
      provide scalable data structures for representing annotated ranges on the genome,
      with special support for transcript structures, read alignments and coverage
      vectors. Computational facilities include efficient algorithms for overlap and
      nearest neighbor detection, coverage calculation and other range operations. This
      infrastructure directly supports more than 80 other Bioconductor packages,
      including those for sequence analysis, differential expression analysis and
      visualization. 

PMID- 23950697
TI  - Binding polymorphism in the DNA bound state of the Pdx1 homeodomain.
AB  - The subtle effects of DNA-protein recognition are illustrated in the homeodomain
      fold. This is one of several small DNA binding motifs that, in spite of limited
      DNA binding specificity, adopts crucial, specific roles when incorporated in a
      transcription factor. The homeodomain is composed of a 3-helix domain and a
      mobile N-terminal arm. Helix 3 (the recognition helix) interacts with the DNA
      bases through the major groove, while the N-terminal arm becomes ordered upon
      binding a specific sequence through the minor groove. Although many structural
      studies have characterized the DNA binding properties of homeodomains, the
      factors behind the binding specificity are still difficult to elucidate. A
      crystal structure of the Pdx1 homeodomain bound to DNA (PDB 2H1K) obtained
      previously in our lab shows two complexes with differences in the conformation of
      the N-terminal arm, major groove contacts, and backbone contacts, raising new
      questions about the DNA recognition process by homeodomains. Here, we carry out
      fully atomistic Molecular Dynamics simulations both in crystal and aqueous
      environments in order to elucidate the nature of the difference in binding
      contacts. The crystal simulations reproduce the X-ray experimental structures
      well. In the absence of crystal packing constraints, the differences between the
      two complexes increase during the solution simulations. Thus, the conformational
      differences are not an artifact of crystal packing. In solution, the homeodomain
      with a disordered N-terminal arm repositions to a partially specific orientation.
      Both the crystal and aqueous simulations support the existence of different
      stable binding conformers identified in the original crystallographic data with
      different degrees of specificity. We propose that protein-protein and protein-DNA
      interactions favor a subset of the possible conformations. This flexibility in
      DNA binding may facilitate multiple functions for the same transcription factor. 

PMID- 23950698
TI  - Evolutionary tradeoffs between economy and effectiveness in biological
      homeostasis systems.
AB  - Biological regulatory systems face a fundamental tradeoff: they must be effective
      but at the same time also economical. For example, regulatory systems that are
      designed to repair damage must be effective in reducing damage, but economical in
      not making too many repair proteins because making excessive proteins carries a
      fitness cost to the cell, called protein burden. In order to see how biological
      systems compromise between the two tasks of effectiveness and economy, we applied
      an approach from economics and engineering called Pareto optimality. This
      approach allows calculating the best-compromise systems that optimally combine
      the two tasks. We used a simple and general model for regulation, known as
      integral feedback, and showed that best-compromise systems have particular
      combinations of biochemical parameters that control the response rate and basal
      level. We find that the optimal systems fall on a curve in parameter space. Due
      to this feature, even if one is able to measure only a small fraction of the
      system's parameters, one can infer the rest. We applied this approach to estimate
      parameters in three biological systems: response to heat shock and response to
      DNA damage in bacteria, and calcium homeostasis in mammals.

PMID- 23950700
TI  - Shape similarity, better than semantic membership, accounts for the structure of
      visual object representations in a population of monkey inferotemporal neurons.
AB  - The anterior inferotemporal cortex (IT) is the highest stage along the hierarchy
      of visual areas that, in primates, processes visual objects. Although several
      lines of evidence suggest that IT primarily represents visual shape information,
      some recent studies have argued that neuronal ensembles in IT code the semantic
      membership of visual objects (i.e., represent conceptual classes such as animate
      and inanimate objects). In this study, we investigated to what extent semantic,
      rather than purely visual information, is represented in IT by performing a
      multivariate analysis of IT responses to a set of visual objects. By relying on a
      variety of machine-learning approaches (including a cutting-edge clustering
      algorithm that has been recently developed in the domain of statistical physics),
      we found that, in most instances, IT representation of visual objects is
      accounted for by their similarity at the level of shape or, more surprisingly,
      low-level visual properties. Only in a few cases we observed IT representations
      of semantic classes that were not explainable by the visual similarity of their
      members. Overall, these findings reassert the primary function of IT as a
      conveyor of explicit visual shape information, and reveal that low-level visual
      properties are represented in IT to a greater extent than previously appreciated.
      In addition, our work demonstrates how combining a variety of state-of-the-art
      multivariate approaches, and carefully estimating the contribution of shape
      similarity to the representation of object categories, can substantially advance
      our understanding of neuronal coding of visual objects in cortex. 

PMID- 23950699
TI  - Top-down beta rhythms support selective attention via interlaminar interaction: a
      model.
AB  - Cortical rhythms have been thought to play crucial roles in our cognitive
      abilities. Rhythmic activity in the beta frequency band, around 20 Hz, has been
      reported in recent studies that focused on neural correlates of attention,
      indicating that top-down beta rhythms, generated in higher cognitive areas and
      delivered to earlier sensory areas, can support attentional gain modulation. To
      elucidate functional roles of beta rhythms and underlying mechanisms, we built a
      computational model of sensory cortical areas. Our simulation results show that
      top-down beta rhythms can activate ascending synaptic projections from L5 to L4
      and L2/3, responsible for biased competition in superficial layers. In the
      simulation, slow-inhibitory interneurons are shown to resonate to the 20 Hz input
      and modulate the activity in superficial layers in an attention-related manner.
      The predicted critical roles of these cells in attentional gain provide a
      potential mechanism by which cholinergic drive can support selective attention. 

PMID- 23950701
TI  - Ultrasensitivity in phosphorylation-dephosphorylation cycles with little
      substrate.
AB  - Cellular decision-making is driven by dynamic behaviours, such as the
      preparations for sunrise enabled by circadian rhythms and the choice of cell
      fates enabled by positive feedback. Such behaviours are often built upon
      ultrasensitive responses where a linear change in input generates a sigmoidal
      change in output. Phosphorylation-dephosphorylation cycles are one means to
      generate ultrasensitivity. Using bioinformatics, we show that in vivo levels of
      kinases and phosphatases frequently exceed the levels of their corresponding
      substrates in budding yeast. This result is in contrast to the conditions often
      required by zero-order ultrasensitivity, perhaps the most well known means for
      how such cycles become ultrasensitive. We therefore introduce a mechanism to
      generate ultrasensitivity when numbers of enzymes are higher than numbers of
      substrates. Our model combines distributive and non-distributive actions of the
      enzymes with two-stage binding and concerted allosteric transitions of the
      substrate. We use analytical and numerical methods to calculate the Hill number
      of the response. For a substrate with [Formula: see text] phosphosites, we find
      an upper bound of the Hill number of [Formula: see text], and so even systems
      with a single phosphosite can be ultrasensitive. Two-stage binding, where an
      enzyme must first bind to a binding site on the substrate before it can access
      the substrate's phosphosites, allows the enzymes to sequester the substrate. Such
      sequestration combined with competition for each phosphosite provides an
      intuitive explanation for the sigmoidal shifts in levels of phosphorylated
      substrate. Additionally, we find cases for which the response is not monotonic,
      but shows instead a peak at intermediate levels of input. Given its generality,
      we expect the mechanism described by our model to often underlay decision-making
      circuits in eukaryotic cells. 

PMID- 23950706
TI  - Biosecurity implications of new technology and discovery in plant virus research.
AB  - Human activity is causing new encounters between viruses and plants.
      Anthropogenic interventions include changing land use, decreasing biodiversity,
      trade, the introduction of new plant and vector species to native landscapes, and
      changing atmospheric and climatic conditions. The discovery of thousands of new
      viruses, especially those associated with healthy-appearing native plants, is
      shifting the paradigm for their role within the ecosystem from foe to friend. The
      cost of new plant virus incursions can be high and result in the loss of trade
      and/or production for short or extended periods. We present and justify three
      recommendations for plant biosecurity to improve communication about plant
      viruses, assist with the identification of viruses and their impacts, and protect
      the high economic, social, environmental, and cultural value of our respective
      nations' unique flora: 1) As part of the burden of proof, countries and
      jurisdictions should identify what pests already exist in, and which pests pose a
      risk to, their native flora; 2) Plant virus sequences not associated with a
      recognized virus infection are designated as "uncultured virus" and tentatively
      named using the host plant species of greatest known prevalence, the word
      "virus," a general location identifier, and a serial number; and 3) Invest in
      basic research to determine the ecology of known and new viruses with existing
      and potential new plant hosts and vectors and develop host-virus pathogenicity
      prediction tools. These recommendations have implications for researchers, risk
      analysts, biosecurity authorities, and policy makers at both a national and an
      international level.

PMID- 23950707
TI  - Role of the nervous system in the control of proteostasis during innate immune
      activation: insights from C. elegans.

PMID- 23950708
TI  - Human genetic susceptibility to invasive aspergillosis.

PMID- 23950709
TI  - A systematic analysis of host factors reveals a Med23-interferon-lambda
      regulatory axis against herpes simplex virus type 1 replication.
AB  - Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral
      or genital skin lesions, meningitis and other diseases particularly harmful in
      immunocompromised individuals. To comprehensively investigate the complex
      interaction between HSV-1 and its host we combined two genome-scale screens for
      host factors (HFs) involved in virus replication. A yeast two-hybrid screen for
      protein interactions and a RNA interference (RNAi) screen with a druggable genome
      small interfering RNA (siRNA) library confirmed existing and identified novel HFs
      which functionally influence HSV-1 infection. Bioinformatic analyses found the
      358 HFs were enriched for several pathways and multi-protein complexes. Of
      particular interest was the identification of Med23 as a strongly anti-viral
      component of the largely pro-viral Mediator complex, which links specific
      transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV
      1 replication was confirmed in gain-of-function gene overexpression experiments,
      and this inhibitory effect was specific to HSV-1, as a range of other viruses
      including Vaccinia virus and Semliki Forest virus were unaffected by Med23
      depletion. We found Med23 significantly upregulated expression of the type III
      interferon family (IFN-lambda) at the mRNA and protein level by directly
      interacting with the transcription factor IRF7. The synergistic effect of Med23
      and IRF7 on IFN-lambda induction suggests this is the major transcription factor
      for IFN-lambda expression. Genotypic analysis of patients suffering recurrent
      orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-lambda
      secretion, found a significant correlation with a single nucleotide polymorphism
      in the IFN-lambda3 (IL28b) promoter strongly linked to Hepatitis C disease and
      treatment outcome. This paper describes a link between Med23 and IFN-lambda,
      provides evidence for the crucial role of IFN-lambda in HSV-1 immune control, and
      highlights the power of integrative genome-scale approaches to identify HFs
      critical for disease progression and outcome.

PMID- 23950710
TI  - acr-23 Encodes a monepantel-sensitive channel in Caenorhabditis elegans.
AB  - Monepantel is a member of the recently identified class of anthelmintics known as
      the amino-acetonitrile derivatives (AADs). Monepantel controls all major gastro
      intestinal nematodes in sheep including those that are resistant to the classical
      anthelmintics. Previous studies have shown that the Caenorhabditis elegans acr-23
      and the Haemonchus contortus Hco-mptl-1 genes may be prominent targets of
      monepantel. With this discovery it became possible to investigate the mode of
      action of monepantel in nematodes at the molecular level. In the present study,
      we show that a C. elegans mutant acr-23 strain is fully rescued by expressing the
      wild-type acr-23 gene. Moreover, we present a new mutant allele, and characterize
      acr-23 alleles genetically. We also show that acr-23 is expressed in body wall
      muscle cells, and provide therefore a possible explanation for the paralysis
      caused by monepantel. Furthermore, genetic evidence suggests that the chaperone
      RIC-3 is required for expression of full monepantel resistance. Finally, we
      present reconstitution of the C. elegans ACR-23 receptor in Xenopus laevis
      oocytes and provide direct evidence of its modulation by monepantel. Conversely,
      co-injection of the chaperone RIC-3 had no impact for channel reconstitution in
      X. laevis oocytes. These results reinforce the involvement of the ACR-23 family
      in the mode of action of monepantel and advance our understanding of this new
      class of anthelmintics.

PMID- 23950711
TI  - The extracellular matrix Component Psl provides fast-acting antibiotic defense in
      Pseudomonas aeruginosa biofilms.
AB  - Bacteria within biofilms secrete and surround themselves with an extracellular
      matrix, which serves as a first line of defense against antibiotic attack.
      Polysaccharides constitute major elements of the biofilm matrix and are implied
      in surface adhesion and biofilm organization, but their contributions to the
      resistance properties of biofilms remain largely elusive. Using a combination of
      static and continuous-flow biofilm experiments we show that Psl, one major
      polysaccharide in the Pseudomonas aeruginosa biofilm matrix, provides a generic
      first line of defense toward antibiotics with diverse biochemical properties
      during the initial stages of biofilm development. Furthermore, we show with mixed
      strain experiments that antibiotic-sensitive "non-producing" cells lacking Psl
      can gain tolerance by integrating into Psl-containing biofilms. However, non
      producers dilute the protective capacity of the matrix and hence, excessive
      incorporation can result in the collapse of resistance of the entire community.
      Our data also reveal that Psl mediated protection is extendible to E. coli and S.
      aureus in co-culture biofilms. Together, our study shows that Psl represents a
      critical first bottleneck to the antibiotic attack of a biofilm community early
      in biofilm development.

PMID- 23950712
TI  - A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RIG-I
      repressor domain in human antiviral innate immune responses.
AB  - The innate immune system is essential for controlling viral infections, but
      several viruses have evolved strategies to escape innate immunity. RIG-I is a
      cytoplasmic viral RNA sensor that triggers the signal to induce type I interferon
      production in response to viral infection. RIG-I activation is regulated by the
      K63-linked polyubiquitin chain mediated by Riplet and TRIM25 ubiquitin ligases.
      TRIM25 is required for RIG-I oligomerization and interaction with the IPS-1
      adaptor molecule. A knockout study revealed that Riplet was essential for RIG-I
      activation. However the molecular mechanism underlying RIG-I activation by Riplet
      remains unclear, and the functional differences between Riplet and TRIM25 are
      also unknown. A genetic study and a pull-down assay indicated that Riplet was
      dispensable for RIG-I RNA binding activity but required for TRIM25 to activate
      RIG-I. Mutational analysis demonstrated that Lys-788 within the RIG-I repressor
      domain was critical for Riplet-mediated K63-linked polyubiquitination and that
      Riplet was required for the release of RIG-I autorepression of its N-terminal
      CARDs, which leads to the association of RIG-I with TRIM25 ubiquitin ligase and
      TBK1 protein kinase. Our data indicate that Riplet is a prerequisite for TRIM25
      to activate RIG-I signaling. We investigated the biological importance of this
      mechanism in human cells and found that hepatitis C virus (HCV) abrogated this
      mechanism. Interestingly, HCV NS3-4A proteases targeted the Riplet protein and
      abrogated endogenous RIG-I polyubiquitination and association with TRIM25 and
      TBK1, emphasizing the biological importance of this mechanism in human antiviral
      innate immunity. In conclusion, our results establish that Riplet-mediated K63
      linked polyubiquitination released RIG-I RD autorepression, which allowed the
      access of positive factors to the RIG-I protein.

PMID- 23950713
TI  - Structure of the parainfluenza virus 5 (PIV5) hemagglutinin-neuraminidase (HN)
      ectodomain.
AB  - Paramyxoviruses cause a wide variety of human and animal diseases. They infect
      host cells using the coordinated action of two surface glycoproteins, the
      receptor binding protein (HN, H, or G) and the fusion protein (F). HN binds
      sialic acid on host cells (hemagglutinin activity) and hydrolyzes these receptors
      during viral egress (neuraminidase activity, NA). Additionally, receptor binding
      is thought to induce a conformational change in HN that subsequently triggers
      major refolding in homotypic F, resulting in fusion of virus and target cell
      membranes. HN is an oligomeric type II transmembrane protein with a short
      cytoplasmic domain and a large ectodomain comprising a long helical stalk and
      large globular head domain containing the enzymatic functions (NA domain).
      Extensive biochemical characterization has revealed that HN-stalk residues
      determine F specificity and activation. However, the F/HN interaction and the
      mechanisms whereby receptor binding regulates F activation are poorly defined.
      Recently, a structure of Newcastle disease virus (NDV) HN ectodomain revealed the
      heads (NA domains) in a "4-heads-down" conformation whereby two of the heads form
      a symmetrical interaction with two sides of the stalk. The interface includes
      stalk residues implicated in triggering F, and the heads sterically shield these
      residues from interaction with F (at least on two sides). Here we report the x
      ray crystal structure of parainfluenza virus 5 (PIV5) HN ectodomain in a "2-heads
      up/2-heads-down" conformation where two heads (covalent dimers) are in the "down
      position," forming a similar interface as observed in the NDV HN ectodomain
      structure, and two heads are in an "up position." The structure supports a model
      in which the heads of HN transition from down to up upon receptor binding thereby
      releasing steric constraints and facilitating the interaction between critical HN
      stalk residues and F.

PMID- 23950714
TI  - SIGIRR, a negative regulator of TLR/IL-1R signalling promotes Microbiota
      dependent resistance to colonization by enteric bacterial pathogens.
AB  - Enteric bacterial pathogens such as enterohemorrhagic E. coli (EHEC) and
      Salmonella Typhimurium target the intestinal epithelial cells (IEC) lining the
      mammalian gastrointestinal tract. Despite expressing innate Toll-like receptors
      (TLRs), IEC are innately hypo-responsive to most bacterial products. This is
      thought to prevent maladaptive inflammatory responses against commensal bacteria,
      but it also limits antimicrobial responses by IEC to invading bacterial
      pathogens, potentially increasing host susceptibility to infection. One reason
      for the innate hypo-responsiveness of IEC is their expression of Single Ig IL-1
      Related Receptor (SIGIRR), a negative regulator of interleukin (IL)-1 and TLR
      signaling. To address whether SIGIRR expression and the innate hypo
      responsiveness of IEC impacts on enteric host defense, Sigirr deficient (-/-)
      mice were infected with the EHEC related pathogen Citrobacter rodentium. Sigirr 
      /- mice responded with accelerated IEC proliferation and strong pro-inflammatory
      and antimicrobial responses but surprisingly, Sigirr -/- mice proved dramatically
      more susceptible to infection than wildtype mice. Through haematopoietic
      transplantation studies, it was determined that SIGIRR expression by non
      haematopoietic cells (putative IEC) regulated these responses. Moreover, the
      exaggerated responses were found to be primarily dependent on IL-1R signaling.
      Whilst exploring the basis for their susceptibility, Sigirr -/- mice were found
      to be unusually susceptible to intestinal Salmonella Typhimurium colonization,
      developing enterocolitis without the typical requirement for antibiotic based
      removal of competing commensal microbes. Strikingly, the exaggerated
      antimicrobial responses seen in Sigirr -/- mice were found to cause a rapid and
      dramatic loss of commensal microbes from the infected intestine. This depletion
      appears to reduce the ability of the microbiota to compete for space and
      nutrients (colonization resistance) with the invading pathogens, leaving the
      intestine highly susceptible to pathogen colonization. Thus, SIGIRR expression by
      IEC reflects a strategy that sacrifices maximal innate responsiveness by IEC in
      order to promote commensal microbe based colonization resistance against
      bacterial pathogens.

PMID- 23950715
TI  - Cytomegalovirus downregulates IRE1 to repress the unfolded protein response.
AB  - During viral infection, a massive demand for viral glycoproteins can overwhelm
      the capacity of the protein folding and quality control machinery, leading to an
      accumulation of unfolded proteins in the endoplasmic reticulum (ER). To restore
      ER homeostasis, cells initiate the unfolded protein response (UPR) by activating
      three ER-to-nucleus signaling pathways, of which the inositol-requiring enzyme 1
      (IRE1)-dependent pathway is the most conserved. To reduce ER stress, the UPR
      decreases protein synthesis, increases degradation of unfolded proteins, and
      upregulates chaperone expression to enhance protein folding. Cytomegaloviruses,
      as other viral pathogens, modulate the UPR to their own advantage. However, the
      molecular mechanisms and the viral proteins responsible for UPR modulation
      remained to be identified. In this study, we investigated the modulation of IRE1
      signaling by murine cytomegalovirus (MCMV) and found that IRE1-mediated mRNA
      splicing and expression of the X-box binding protein 1 (XBP1) is repressed in
      infected cells. By affinity purification, we identified the viral M50 protein as
      an IRE1-interacting protein. M50 expression in transfected or MCMV-infected cells
      induced a substantial downregulation of IRE1 protein levels. The N-terminal
      conserved region of M50 was found to be required for interaction with and
      downregulation of IRE1. Moreover, UL50, the human cytomegalovirus (HCMV) homolog
      of M50, affected IRE1 in the same way. Thus we concluded that IRE1 downregulation
      represents a previously undescribed viral strategy to curb the UPR.

PMID- 23950716
TI  - Identification of new PNEPs indicates a substantial non-PEXEL exportome and
      underpins common features in Plasmodium falciparum protein export.
AB  - Malaria blood stage parasites export a large number of proteins into their host
      erythrocyte to change it from a container of predominantly hemoglobin optimized
      for the transport of oxygen into a niche for parasite propagation. To understand
      this process, it is crucial to know which parasite proteins are exported into the
      host cell. This has been aided by the PEXEL/HT sequence, a five-residue motif
      found in many exported proteins, leading to the prediction of the exportome.
      However, several PEXEL/HT negative exported proteins (PNEPs) indicate that this
      exportome is incomplete and it remains unknown if and how many further PNEPs
      exist. Here we report the identification of new PNEPs in the most virulent
      malaria parasite Plasmodium falciparum. This includes proteins with a domain
      structure deviating from previously known PNEPs and indicates that PNEPs are not
      a rare exception. Unexpectedly, this included members of the MSP-7 related
      protein (MSRP) family, suggesting unanticipated functions of MSRPs. Analyzing
      regions mediating export of selected new PNEPs, we show that the first 20 amino
      acids of PNEPs without a classical N-terminal signal peptide are sufficient to
      promote export of a reporter, confirming the concept that this is a shared
      property of all PNEPs of this type. Moreover, we took advantage of newly found
      soluble PNEPs to show that this type of exported protein requires unfolding to
      move from the parasitophorous vacuole (PV) into the host cell. This indicates
      that soluble PNEPs, like PEXEL/HT proteins, are exported by translocation across
      the PV membrane (PVM), highlighting protein translocation in the parasite
      periphery as a general means in protein export of malaria parasites.

PMID- 23950717
TI  - Crystal Structure of the full-length Japanese encephalitis virus NS5 reveals a
      conserved methyltransferase-polymerase interface.
AB  - The flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ~ 265
      residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part.
      One of the major interests and challenges in NS5 is to understand the interplay
      between RdRP and MTase as a unique natural fusion protein in viral genome
      replication and cap formation. Here, we report the first crystal structure of the
      full-length flavivirus NS5 from Japanese encephalitis virus. The structure
      completes the vision for polymerase motifs F and G, and depicts defined intra
      molecular interactions between RdRP and MTase. Key hydrophobic residues in the
      RdRP-MTase interface are highly conserved in flaviviruses, indicating the
      biological relevance of the observed conformation. Our work paves the way for
      further dissection of the inter-regulations of the essential enzymatic activities
      of NS5 and exploration of possible other conformations of NS5 under different
      circumstances.

PMID- 23950718
TI  - Metabolic features of Protochlamydia amoebophila elementary bodies--a link
      between activity and infectivity in Chlamydiae.
AB  - The Chlamydiae are a highly successful group of obligate intracellular bacteria,
      whose members are remarkably diverse, ranging from major pathogens of humans and
      animals to symbionts of ubiquitous protozoa. While their infective developmental
      stage, the elementary body (EB), has long been accepted to be completely
      metabolically inert, it has recently been shown to sustain some activities,
      including uptake of amino acids and protein biosynthesis. In the current study,
      we performed an in-depth characterization of the metabolic capabilities of EBs of
      the amoeba symbiont Protochlamydia amoebophila. A combined metabolomics approach,
      including fluorescence microscopy-based assays, isotope-ratio mass spectrometry
      (IRMS), ion cyclotron resonance Fourier transform mass spectrometry (ICR/FT-MS),
      and ultra-performance liquid chromatography mass spectrometry (UPLC-MS) was
      conducted, with a particular focus on the central carbon metabolism. In addition,
      the effect of nutrient deprivation on chlamydial infectivity was analyzed. Our
      investigations revealed that host-free P. amoebophila EBs maintain respiratory
      activity and metabolize D-glucose, including substrate uptake as well as host
      free synthesis of labeled metabolites and release of labeled CO2 from (13)C
      labeled D-glucose. The pentose phosphate pathway was identified as major route of
      D-glucose catabolism and host-independent activity of the tricarboxylic acid
      (TCA) cycle was observed. Our data strongly suggest anabolic reactions in P.
      amoebophila EBs and demonstrate that under the applied conditions D-glucose
      availability is essential to sustain metabolic activity. Replacement of this
      substrate by L-glucose, a non-metabolizable sugar, led to a rapid decline in the
      number of infectious particles. Likewise, infectivity of Chlamydia trachomatis, a
      major human pathogen, also declined more rapidly in the absence of nutrients.
      Collectively, these findings demonstrate that D-glucose is utilized by P.
      amoebophila EBs and provide evidence that metabolic activity in the extracellular
      stage of chlamydiae is of major biological relevance as it is a critical factor
      affecting maintenance of infectivity.

PMID- 23950719
TI  - Stabilization of Myc through heterotypic poly-ubiquitination by mLANA is critical
      for gamma-herpesvirus lymphoproliferation.
AB  - Host colonization by lymphotropic gamma-herpesviruses depends critically on
      expansion of viral genomes in germinal center (GC) B-cells. Myc is essential for
      the formation and maintenance of GCs. Yet, the role of Myc in the pathogenesis of
      gamma-herpesviruses is still largely unknown. In this study, Myc was shown to be
      essential for the lymphotropic gamma-herpesvirus MuHV-4 biology as infected cells
      exhibited increased expression of Myc signature genes and the virus was unable to
      expand in Myc defficient GC B-cells. We describe a novel strategy of a viral
      protein activating Myc through increased protein stability resulting in increased
      progression through the cell cycle. This is acomplished by modulating a
      physiological post-translational regulatory pathway of Myc. The molecular
      mechanism involves Myc heterotypic poly-ubiquitination mediated via the viral E3
      ubiquitin-ligase mLANA protein. EC5S(mLANA) modulates cellular control of Myc
      turnover by antagonizing SCF(Fbw7) mediated proteasomal degradation of Myc,
      mimicking SCF(beta-TrCP). The findings here reported reveal that modulation of
      Myc is essential for gamma-herpesvirus persistent infection, establishing a link
      between virus induced lymphoproliferation and disease.

PMID- 23950720
TI  - Brucella modulates secretory trafficking via multiple type IV secretion effector
      proteins.
AB  - The intracellular pathogenic bacterium Brucella generates a replicative vacuole
      (rBCV) derived from the endoplasmic reticulum via subversion of the host cell
      secretory pathway. rBCV biogenesis requires the expression of the Type IV
      secretion system (T4SS) VirB, which is thought to translocate effector proteins
      that modulate membrane trafficking along the endocytic and secretory pathways. To
      date, only a few T4SS substrates have been identified, whose molecular functions
      remain unknown. Here, we used an in silico screen to identify putative T4SS
      effector candidate proteins using criteria such as limited homology in other
      bacterial genera, the presence of features similar to known VirB T4SS effectors,
      GC content and presence of eukaryotic-like motifs. Using beta-lactamase and CyaA
      adenylate cyclase reporter assays, we identified eleven proteins translocated
      into host cells by Brucella, five in a VirB T4SS-dependent manner, namely
      BAB1_0678 (BspA), BAB1_0712 (BspB), BAB1_0847 (BspC), BAB1_1671 (BspE) and
      BAB1_1948 (BspF). A subset of the translocated proteins targeted secretory
      pathway compartments when ectopically expressed in HeLa cells, and the VirB
      effectors BspA, BspB and BspF inhibited protein secretion. Brucella infection
      also impaired host protein secretion in a process requiring BspA, BspB and BspF.
      Single or combined deletions of bspA, bspB and bspF affected Brucella ability to
      replicate in macrophages and persist in the liver of infected mice. Taken
      together, these findings demonstrate that Brucella modulates secretory
      trafficking via multiple T4SS effector proteins that likely act coordinately to
      promote Brucella pathogenesis.

PMID- 23950722
TI  - Female behaviour drives expression and evolution of gustatory receptors in
      butterflies.
AB  - Secondary plant compounds are strong deterrents of insect oviposition and
      feeding, but may also be attractants for specialist herbivores. These insect
      plant interactions are mediated by insect gustatory receptors (Grs) and olfactory
      receptors (Ors). An analysis of the reference genome of the butterfly Heliconius
      melpomene, which feeds on passion-flower vines (Passiflora spp.), together with
      whole-genome sequencing within the species and across the Heliconius phylogeny
      has permitted an unprecedented opportunity to study the patterns of gene
      duplication and copy-number variation (CNV) among these key sensory genes. We
      report in silico gene predictions of 73 Gr genes in the H. melpomene reference
      genome, including putative CO2, sugar, sugar alcohol, fructose, and bitter
      receptors. The majority of these Grs are the result of gene duplications since
      Heliconius shared a common ancestor with the monarch butterfly or the silkmoth.
      Among Grs but not Ors, CNVs are more common within species in those gene lineages
      that have also duplicated over this evolutionary time-scale, suggesting ongoing
      rapid gene family evolution. Deep sequencing (~1 billion reads) of transcriptomes
      from proboscis and labial palps, antennae, and legs of adult H. melpomene males
      and females indicates that 67 of the predicted 73 Gr genes and 67 of the 70
      predicted Or genes are expressed in these three tissues. Intriguingly, we find
      that one-third of all Grs show female-biased gene expression (n = 26) and nearly
      all of these (n = 21) are Heliconius-specific Grs. In fact, a significant excess
      of Grs that are expressed in female legs but not male legs are the result of
      recent gene duplication. This difference in Gr gene expression diversity between
      the sexes is accompanied by a striking sexual dimorphism in the abundance of
      gustatory sensilla on the forelegs of H. melpomene, suggesting that female
      oviposition behaviour drives the evolution of new gustatory receptors in
      butterfly genomes.

PMID- 23950723
TI  - Gene expression regulation by upstream open reading frames and human disease.
AB  - Upstream open reading frames (uORFs) are major gene expression regulatory
      elements. In many eukaryotic mRNAs, one or more uORFs precede the initiation
      codon of the main coding region. Indeed, several studies have revealed that
      almost half of human transcripts present uORFs. Very interesting examples have
      shown that these uORFs can impact gene expression of the downstream main ORF by
      triggering mRNA decay or by regulating translation. Also, evidence from recent
      genetic and bioinformatic studies implicates disturbed uORF-mediated
      translational control in the etiology of many human diseases, including
      malignancies, metabolic or neurologic disorders, and inherited syndromes. In this
      review, we will briefly present the mechanisms through which uORFs regulate gene
      expression and how they can impact on the organism's response to different cell
      stress conditions. Then, we will emphasize the importance of these structures by
      illustrating, with specific examples, how disturbed uORF-mediated translational
      control can be involved in the etiology of human diseases, giving special
      importance to genotype-phenotype correlations. Identifying and studying more
      cases of uORF-altering mutations will help us to understand and establish
      genotype-phenotype associations, leading to advancements in diagnosis, prognosis,
      and treatment of many human disorders.

PMID- 23950724
TI  - Re-ranking sequencing variants in the post-GWAS era for accurate causal variant
      identification.
AB  - Next generation sequencing has dramatically increased our ability to localize
      disease-causing variants by providing base-pair level information at costs
      increasingly feasible for the large sample sizes required to detect complex-trait
      associations. Yet, identification of causal variants within an established region
      of association remains a challenge. Counter-intuitively, certain factors that
      increase power to detect an associated region can decrease power to localize the
      causal variant. First, combining GWAS with imputation or low coverage sequencing
      to achieve the large sample sizes required for high power can have the unintended
      effect of producing differential genotyping error among SNPs. This tends to bias
      the relative evidence for association toward better genotyped SNPs. Second, re
      use of GWAS data for fine-mapping exploits previous findings to ensure genome
      wide significance in GWAS-associated regions. However, using GWAS findings to
      inform fine-mapping analysis can bias evidence away from the causal SNP toward
      the tag SNP and SNPs in high LD with the tag. Together these factors can reduce
      power to localize the causal SNP by more than half. Other strategies commonly
      employed to increase power to detect association, namely increasing sample size
      and using higher density genotyping arrays, can, in certain common scenarios,
      actually exacerbate these effects and further decrease power to localize causal
      variants. We develop a re-ranking procedure that accounts for these adverse
      effects and substantially improves the accuracy of causal SNP identification,
      often doubling the probability that the causal SNP is top-ranked. Application to
      the NCI BPC3 aggressive prostate cancer GWAS with imputation meta-analysis
      identified a new top SNP at 2 of 3 associated loci and several additional
      possible causal SNPs at these loci that may have otherwise been overlooked. This
      method is simple to implement using R scripts provided on the author's website.

PMID- 23950725
TI  - Sociogenomics of cooperation and conflict during colony founding in the fire ant
      Solenopsis invicta.
AB  - One of the fundamental questions in biology is how cooperative and altruistic
      behaviors evolved. The majority of studies seeking to identify the genes
      regulating these behaviors have been performed in systems where behavioral and
      physiological differences are relatively fixed, such as in the honey bee. During
      colony founding in the monogyne (one queen per colony) social form of the fire
      ant Solenopsis invicta, newly-mated queens may start new colonies either
      individually (haplometrosis) or in groups (pleometrosis). However, only one queen
      (the "winner") in pleometrotic associations survives and takes the lead of the
      young colony while the others (the "losers") are executed. Thus, colony founding
      in fire ants provides an excellent system in which to examine the genes
      underpinning cooperative behavior and how the social environment shapes the
      expression of these genes. We developed a new whole genome microarray platform
      for S. invicta to characterize the gene expression patterns associated with
      colony founding behavior. First, we compared haplometrotic queens, pleometrotic
      winners and pleometrotic losers. Second, we manipulated pleometrotic couples in
      order to switch or maintain the social ranks of the two cofoundresses.
      Haplometrotic and pleometrotic queens differed in the expression of genes
      involved in stress response, aging, immunity, reproduction and lipid
      biosynthesis. Smaller sets of genes were differentially expressed between winners
      and losers. In the second experiment, switching social rank had a much greater
      impact on gene expression patterns than the initial/final rank. Expression
      differences for several candidate genes involved in key biological processes were
      confirmed using qRT-PCR. Our findings indicate that, in S. invicta, social
      environment plays a major role in the determination of the patterns of gene
      expression, while the queen's physiological state is secondary. These results
      highlight the powerful influence of social environment on regulation of the
      genomic state, physiology and ultimately, social behavior of animals.

PMID- 23950726
TI  - GUESS-ing polygenic associations with multiple phenotypes using a GPU-based
      evolutionary stochastic search algorithm.
AB  - Genome-wide association studies (GWAS) yielded significant advances in defining
      the genetic architecture of complex traits and disease. Still, a major hurdle of
      GWAS is narrowing down multiple genetic associations to a few causal variants for
      functional studies. This becomes critical in multi-phenotype GWAS where detection
      and interpretability of complex SNP(s)-trait(s) associations are complicated by
      complex Linkage Disequilibrium patterns between SNPs and correlation between
      traits. Here we propose a computationally efficient algorithm (GUESS) to explore
      complex genetic-association models and maximize genetic variant detection. We
      integrated our algorithm with a new Bayesian strategy for multi-phenotype
      analysis to identify the specific contribution of each SNP to different trait
      combinations and study genetic regulation of lipid metabolism in the Gutenberg
      Health Study (GHS). Despite the relatively small size of GHS (n  =  3,175), when
      compared with the largest published meta-GWAS (n > 100,000), GUESS recovered most
      of the major associations and was better at refining multi-trait associations
      than alternative methods. Amongst the new findings provided by GUESS, we revealed
      a strong association of SORT1 with TG-APOB and LIPC with TG-HDL phenotypic
      groups, which were overlooked in the larger meta-GWAS and not revealed by
      competing approaches, associations that we replicated in two independent cohorts.
      Moreover, we demonstrated the increased power of GUESS over alternative multi
      phenotype approaches, both Bayesian and non-Bayesian, in a simulation study that
      mimics real-case scenarios. We showed that our parallel implementation based on
      Graphics Processing Units outperforms alternative multi-phenotype methods. Beyond
      multivariate modelling of multi-phenotypes, our Bayesian model employs a flexible
      hierarchical prior structure for genetic effects that adapts to any correlation
      structure of the predictors and increases the power to identify associated
      variants. This provides a powerful tool for the analysis of diverse genomic
      features, for instance including gene expression and exome sequencing data, where
      complex dependencies are present in the predictor space.

PMID- 23950727
TI  - Global analysis of the sporulation pathway of Clostridium difficile.
AB  - The Gram-positive, spore-forming pathogen Clostridium difficile is the leading
      definable cause of healthcare-associated diarrhea worldwide. C. difficile
      infections are difficult to treat because of their frequent recurrence, which can
      cause life-threatening complications such as pseudomembranous colitis. The spores
      of C. difficile are responsible for these high rates of recurrence, since they
      are the major transmissive form of the organism and resistant to antibiotics and
      many disinfectants. Despite the importance of spores to the pathogenesis of C.
      difficile, little is known about their composition or formation. Based on studies
      in Bacillus subtilis and other Clostridium spp., the sigma factors sigma(F),
      sigma(E), sigma(G), and sigma(K) are predicted to control the transcription of
      genes required for sporulation, although their specific functions vary depending
      on the organism. In order to determine the roles of sigma(F), sigma(E), sigma(G),
      and sigma(K) in regulating C. difficile sporulation, we generated loss-of
      function mutations in genes encoding these sporulation sigma factors and
      performed RNA-Sequencing to identify specific sigma factor-dependent genes. This
      analysis identified 224 genes whose expression was collectively activated by
      sporulation sigma factors: 183 were sigma(F)-dependent, 169 were sigma(E)
      dependent, 34 were sigma(G)-dependent, and 31 were sigma(K)-dependent. In
      contrast with B. subtilis, C. difficile sigma(E) was dispensable for sigma(G)
      activation, sigma(G) was dispensable for sigma(K) activation, and sigma(F) was
      required for post-translationally activating sigma(G). Collectively, these
      results provide the first genome-wide transcriptional analysis of genes induced
      by specific sporulation sigma factors in the Clostridia and highlight that
      diverse mechanisms regulate sporulation sigma factor activity in the Firmicutes.

PMID- 23950728
TI  - Myc-driven overgrowth requires unfolded protein response-mediated induction of
      autophagy and antioxidant responses in Drosophila melanogaster.
AB  - Autophagy, a lysosomal self-degradation and recycling pathway, plays dual roles
      in tumorigenesis. Autophagy deficiency predisposes to cancer, at least in part,
      through accumulation of the selective autophagy cargo p62, leading to activation
      of antioxidant responses and tumor formation. While cell growth and autophagy are
      inversely regulated in most cells, elevated levels of autophagy are observed in
      many established tumors, presumably mediating survival of cancer cells. Still,
      the relationship of autophagy and oncogenic signaling is poorly characterized.
      Here we show that the evolutionarily conserved transcription factor Myc (dm), a
      proto-oncogene involved in cell growth and proliferation, is also a physiological
      regulator of autophagy in Drosophila melanogaster. Loss of Myc activity in null
      mutants or in somatic clones of cells inhibits autophagy. Forced expression of
      Myc results in cell-autonomous increases in cell growth, autophagy induction, and
      p62 (Ref2P)-mediated activation of Nrf2 (cnc), a transcription factor promoting
      antioxidant responses. Mechanistically, Myc overexpression increases unfolded
      protein response (UPR), which leads to PERK-dependent autophagy induction and may
      be responsible for p62 accumulation. Genetic or pharmacological inhibition of
      UPR, autophagy or p62/Nrf2 signaling prevents Myc-induced overgrowth, while these
      pathways are dispensable for proper growth of control cells. In addition, we show
      that the autophagy and antioxidant pathways are required in parallel for excess
      cell growth driven by Myc. Deregulated expression of Myc drives tumor progression
      in most human cancers, and UPR and autophagy have been implicated in the survival
      of Myc-dependent cancer cells. Our data obtained in a complete animal show that
      UPR, autophagy and p62/Nrf2 signaling are required for Myc-dependent cell growth.
      These novel results give additional support for finding future approaches to
      specifically inhibit the growth of cancer cells addicted to oncogenic Myc.

PMID- 23950729
TI  - The C. elegans DSB-2 protein reveals a regulatory network that controls
      competence for meiotic DSB formation and promotes crossover assurance.
AB  - For most organisms, chromosome segregation during meiosis relies on deliberate
      induction of DNA double-strand breaks (DSBs) and repair of a subset of these DSBs
      as inter-homolog crossovers (COs). However, timing and levels of DSB formation
      must be tightly controlled to avoid jeopardizing genome integrity. Here we
      identify the DSB-2 protein, which is required for efficient DSB formation during
      C. elegans meiosis but is dispensable for later steps of meiotic recombination.
      DSB-2 localizes to chromatin during the time of DSB formation, and its
      disappearance coincides with a decline in RAD-51 foci marking early recombination
      intermediates and precedes appearance of COSA-1 foci marking CO-designated sites.
      These and other data suggest that DSB-2 and its paralog DSB-1 promote competence
      for DSB formation. Further, immunofluorescence analyses of wild-type gonads and
      various meiotic mutants reveal that association of DSB-2 with chromatin is
      coordinated with multiple distinct aspects of the meiotic program, including the
      phosphorylation state of nuclear envelope protein SUN-1 and dependence on RAD-50
      to load the RAD-51 recombinase at DSB sites. Moreover, association of DSB-2 with
      chromatin is prolonged in mutants impaired for either DSB formation or formation
      of downstream CO intermediates. These and other data suggest that association of
      DSB-2 with chromatin is an indicator of competence for DSB formation, and that
      cells respond to a deficit of CO-competent recombination intermediates by
      prolonging the DSB-competent state. In the context of this model, we propose that
      formation of sufficient CO-competent intermediates engages a negative feedback
      response that leads to cessation of DSB formation as part of a major coordinated
      transition in meiotic prophase progression. The proposed negative feedback
      regulation of DSB formation simultaneously (1) ensures that sufficient DSBs are
      made to guarantee CO formation and (2) prevents excessive DSB levels that could
      have deleterious effects.

PMID- 23950730
TI  - Genome-wide DNA methylation analysis of systemic lupus erythematosus reveals
      persistent hypomethylation of interferon genes and compositional changes to CD4+
      T-cell populations.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease with known genetic,
      epigenetic, and environmental risk factors. To assess the role of DNA methylation
      in SLE, we collected CD4+ T-cells, CD19+ B-cells, and CD14+ monocytes from 49 SLE
      patients and 58 controls, and performed genome-wide DNA methylation analysis with
      Illumina Methylation 450 microarrays. We identified 166 CpGs in B-cells, 97 CpGs
      in monocytes, and 1,033 CpGs in T-cells with highly significant changes in DNA
      methylation levels (p < 1 * 10(-8)) among SLE patients. Common to all three cell
      types were widespread and severe hypomethylation events near genes involved in
      interferon signaling (type I). These interferon-related changes were apparent in
      patients collected during active and quiescent stages of the disease, suggesting
      that epigenetically-mediated hypersensitivity to interferon persists beyond acute
      stages of the disease and is independent of circulating interferon levels. This
      interferon hypersensitivity was apparent in memory, naive and regulatory T-cells,
      suggesting that this epigenetic state in lupus patients is established in
      progenitor cell populations. We also identified a widespread, but lower amplitude
      shift in methylation in CD4+ T-cells (> 16,000 CpGs at FDR < 1%) near genes
      involved in cell division and MAPK signaling. These cell type-specific effects
      are consistent with disease-specific changes in the composition of the CD4+
      population and suggest that shifts in the proportion of CD4+ subtypes can be
      monitored at CpGs with subtype-specific DNA methylation patterns.

PMID- 23950733
TI  - The innocence project at twenty: an interview with Barry Scheck. Interview by
      Jane Gitschier.

PMID- 23950731
TI  - Ras1 acts through duplicated Cdc42 and Rac proteins to regulate morphogenesis and
      pathogenesis in the human fungal pathogen Cryptococcus neoformans.
AB  - Proliferation and morphogenesis in eukaryotic cells depend on the concerted
      activity of Rho-type GTPases, including Ras, Cdc42, and Rac. The sexually
      dimorphic fungus Cryptococcus neoformans, which encodes paralogous, non-essential
      copies of all three, provides a unique model in which to examine the interactions
      of these conserved proteins. Previously, we demonstrated that RAS1 mediates C.
      neoformans virulence by acting as a central regulator of both thermotolerance and
      mating. We report here that ras1Delta mutants accumulate defects in polarized
      growth, cytokinesis, and cell cycle progression. We demonstrate that the
      ras1Delta defects in thermotolerance and mating can be largely explained by the
      compromised activity of four downstream Rho-GTPases: the Cdc42 paralogs, Cdc42
      and Cdc420; and the Rac paralogs, Rac1 and Rac2. Further, we demonstrate that the
      separate GTPase classes play distinct Ras-dependent roles in C. neoformans
      morphogenesis and pathogenesis. Cdc42 paralogs primarily control septin
      localization and cytokinesis, while Rac paralogs play a primary role in polarized
      cell growth. Together, these duplicate, related signaling proteins provide a
      robust system to allow microbial proliferation in the presence of host-derived
      cell stresses.

PMID- 23950732
TI  - Masculinization of the x chromosome in the pea aphid.
AB  - Evolutionary theory predicts that sexually antagonistic mutations accumulate
      differentially on the X chromosome and autosomes in species with an XY sex
      determination system, with effects (masculinization or feminization of the X)
      depending on the dominance of mutations. Organisms with alternative modes of
      inheritance of sex chromosomes offer interesting opportunities for studying
      sexual conflicts and their resolution, because expectations for the preferred
      genomic location of sexually antagonistic alleles may differ from standard
      systems. Aphids display an XX/X0 system and combine an unusual inheritance of the
      X chromosome with the alternation of sexual and asexual reproduction. In this
      study, we first investigated theoretically the accumulation of sexually
      antagonistic mutations on the aphid X chromosome. Our results show that i) the X
      is always more favourable to the spread of male-beneficial alleles than
      autosomes, and should thus be enriched in sexually antagonistic alleles
      beneficial for males, ii) sexually antagonistic mutations beneficial for asexual
      females accumulate preferentially on autosomes, iii) in contrast to predictions
      for standard systems, these qualitative results are not affected by the dominance
      of mutations. Under the assumption that sex-biased gene expression evolves to
      solve conflicts raised by the spread of sexually antagonistic alleles, one
      expects that male-biased genes should be enriched on the X while asexual female
      biased genes should be enriched on autosomes. Using gene expression data (RNA
      Seq) in males, sexual females and asexual females of the pea aphid, we confirm
      these theoretical predictions. Although other mechanisms than the resolution of
      sexual antagonism may lead to sex-biased gene expression, we argue that they
      could hardly explain the observed difference between X and autosomes. On top of
      reporting a strong masculinization of the aphid X chromosome, our study
      highlights the relevance of organisms displaying an alternative mode of sex
      chromosome inheritance to understanding the forces shaping chromosome evolution.

PMID- 23950734
TI  - An essential function for the ATR-activation-domain (AAD) of TopBP1 in mouse
      development and cellular senescence.
AB  - ATR activation is dependent on temporal and spatial interactions with partner
      proteins. In the budding yeast model, three proteins - Dpb11(TopBP1), Ddc1(Rad9)
      and Dna2 - all interact with and activate Mec1(ATR). Each contains an ATR
      activation domain (ADD) that interacts directly with the Mec1(ATR):Ddc2(ATRIP)
      complex. Any of the Dpb11(TopBP1), Ddc1(Rad9) or Dna2 ADDs is sufficient to
      activate Mec1(ATR) in vitro. All three can also independently activate Mec1(ATR)
      in vivo: the checkpoint is lost only when all three AADs are absent. In
      metazoans, only TopBP1 has been identified as a direct ATR activator. Depletion
      replacement approaches suggest the TopBP1-AAD is both sufficient and necessary
      for ATR activation. The physiological function of the TopBP1 AAD is, however,
      unknown. We created a knock-in point mutation (W1147R) that ablates mouse TopBP1
      AAD function. TopBP1-W1147R is early embryonic lethal. To analyse TopBP1-W1147R
      cellular function in vivo, we silenced the wild type TopBP1 allele in
      heterozygous MEFs. AAD inactivation impaired cell proliferation, promoted
      premature senescence and compromised Chk1 signalling following UV irradiation. We
      also show enforced TopBP1 dimerization promotes ATR-dependent Chk1
      phosphorylation. Our data suggest that, unlike the yeast models, the TopBP1-AAD
      is the major activator of ATR, sustaining cell proliferation and embryonic
      development.

PMID- 23950736
TI  - Combining Transition Metal Catalysis with Radical Chemistry: Dramatic
      Acceleration of Palladium-Catalyzed C-H Arylation with Diaryliodonium Salts.
AB  - This paper describes a photoredox palladium/iridium-catalyzed C-H arylation with
      diaryliodonium reagents. Details of the reaction optimization, substrate scope,
      and mechanism are presented along with a comparison to a related method in which
      aryldiazonium salts are used in place of diaryliodonium reagents. The
      unprecedentedly mild reaction conditions (25 oC in methanol), the requirement for
      light and a photocatalyst, the inhibitory effect of radical scavengers, and the
      observed chemoselectivity trends are all consistent with a radical-thermal
      reaction with diaryliodonium reagents that is believed to proceed via an 'ionic'
      2e- pathway and requires a much higher reaction temperature (100 oC).

PMID- 23950735
TI  - Global analysis of fission yeast mating genes reveals new autophagy factors.
AB  - Macroautophagy (autophagy) is crucial for cell survival during starvation and
      plays important roles in animal development and human diseases. Molecular
      understanding of autophagy has mainly come from the budding yeast Saccharomyces
      cerevisiae, and it remains unclear to what extent the mechanisms are the same in
      other organisms. Here, through screening the mating phenotype of a genome-wide
      deletion collection of the fission yeast Schizosaccharomyces pombe, we obtained a
      comprehensive catalog of autophagy genes in this highly tractable organism,
      including genes encoding three heretofore unidentified core Atg proteins, Atg10,
      Atg14, and Atg16, and two novel factors, Ctl1 and Fsc1. We systematically
      examined the subcellular localization of fission yeast autophagy factors for the
      first time and characterized the phenotypes of their mutants, thereby uncovering
      both similarities and differences between the two yeasts. Unlike budding yeast,
      all three Atg18/WIPI proteins in fission yeast are essential for autophagy, and
      we found that they play different roles, with Atg18a uniquely required for the
      targeting of the Atg12-Atg5.Atg16 complex. Our investigation of the two novel
      factors revealed unforeseen autophagy mechanisms. The choline transporter-like
      protein Ctl1 interacts with Atg9 and is required for autophagosome formation. The
      fasciclin domain protein Fsc1 localizes to the vacuole membrane and is required
      for autophagosome-vacuole fusion but not other vacuolar fusion events. Our study
      sheds new light on the evolutionary diversity of the autophagy machinery and
      establishes the fission yeast as a useful model for dissecting the mechanisms of
      autophagy.

PMID- 23950737
TI  - L-type CaV1.2 deletion in the cochlea but not in the brainstem reduces noise
      vulnerability: implication for CaV1.2-mediated control of cochlear BDNF
      expression.
AB  - Voltage-gated L-type Ca(2+) channels (L-VGCCs) like CaV1.2 are assumed to play a
      crucial role for controlling release of trophic peptides including brain-derived
      neurotrophic factor (BDNF). In the inner ear of the adult mouse, besides the well
      described L-VGCC CaV1.3, CaV1.2 is also expressed. Due to lethality of
      constitutive CaV1.2 knock-out mice, the function of this ion channel as well as
      its putative relationship to BDNF in the auditory system is entirely elusive. We
      recently described that BDNF plays a differential role for inner hair cell (IHC)
      vesicles release in normal and traumatized condition. To elucidate a presumptive
      role of CaV1.2 during this process, two tissue-specific conditional mouse lines
      were generated. To distinguish the impact of CaV1.2 on the cochlea from that on
      feedback loops from higher auditory centers CaV1.2 was deleted, in one mouse
      line, under the Pax2 promoter (CaV1.2(Pax2)) leading to a deletion in the spiral
      ganglion neurons, dorsal cochlear nucleus, and inferior colliculus. In the second
      mouse line, the Egr2 promoter was used for deleting CaV1.2 (CaV1.2(Egr2)) in
      auditory brainstem nuclei. In both mouse lines, normal hearing threshold and
      equal number of IHC release sites were observed. We found a slight reduction of
      auditory brainstem response wave I amplitudes in the CaV1.2(Pax2) mice, but not
      in the CaV1.2(Egr2) mice. After noise exposure, CaV1.2(Pax2) mice had less
      pronounced hearing loss that correlated with maintenance of ribbons in IHCs and
      less reduced activity in auditory nerve fibers, as well as in higher brain
      centers at supra-threshold sound stimulation. As reduced cochlear BDNF mRNA
      levels were found in CaV1.2(Pax2) mice, we suggest that a CaV1.2-dependent step
      may participate in triggering part of the beneficial and deteriorating effects of
      cochlear BDNF in intact systems and during noise exposure through a pathway that
      is independent of CaV1.2 function in efferent circuits. 

PMID- 23950738
TI  - What does the mediodorsal thalamus do?
AB  - Dense amnesia can result from damage to the medial diencephalon in humans and in
      animals. In humans this damage is diffuse and can include the mediodorsal nuclei
      of the thalamus. In animal models, lesion studies have confirmed the mediodorsal
      thalamus (MD) has a role in memory and other cognitive tasks, although the extent
      of deficits is mixed. Anatomical tracing studies confirm at least three different
      subgroupings of the MD: medial, central, and lateral, each differentially
      interconnected to the prefrontal cortex (PFC). Moreover, these subgroupings of
      the MD also receive differing inputs from other brain structures, including the
      basal ganglia thus the MD subgroupings form key nodes in interconnected frontal
      striatal-thalamic neural circuits, integrating critical information within the
      PFC. We will provide a review of data collected from non-human primates and
      rodents after selective brain injury to the whole of the MD as well as these
      subgroupings to highlight the extent of deficits in various cognitive tasks. This
      research highlights the neural basis of memory and cognitive deficits associated
      with the subgroupings of the MD and their interconnected neural networks. The
      evidence shows that the MD plays a critical role in many varied cognitive
      processes. In addition, the MD is actively processing information and integrating
      it across these neural circuits for successful cognition. Having established that
      the MD is critical for memory and cognition, further research is required to
      understand how the MD specifically influences these cognitive processing carried
      out by the brain. 

PMID- 23950739
TI  - The endocannabinoid system as a possible target to treat both the cognitive and
      emotional features of post-traumatic stress disorder (PTSD).
AB  - Post-traumatic stress disorder (PTSD) is a psychiatric disorder of significant
      prevalence and morbidity, whose pathogenesis relies on paradoxical changes of
      emotional memory processing. An ideal treatment would be a drug able to block the
      pathological over-consolidation and continuous retrieval of the traumatic event,
      while enhancing its extinction and reducing the anxiety symptoms. While the
      latter benefit from antidepressant medications, no drug is available to control
      the cognitive symptomatology. Endocannabinoids regulate affective states and
      participate in memory consolidation, retrieval, and extinction. Clinical findings
      showing a relationship between Cannabis use and PTSD, as well as changes in
      endocannabinoid activity in PTSD patients, further suggest the existence of a
      link between endocannabinoids and maladaptive brain changes after trauma
      exposure. Along these lines, we suggest that endocannabinoid degradation
      inhibitors may be an ideal therapeutic approach to simultaneously treat the
      emotional and cognitive features of PTSD, avoiding the unwanted psychotropic
      effects of compounds directly binding cannabinoid receptors. 

PMID- 23950740
TI  - Automatic processing of unattended lexical information in visual oddball
      presentation: neurophysiological evidence.
AB  - Previous electrophysiological studies of automatic language processing revealed
      early (100-200 ms) reflections of access to lexical characteristics of speech
      signal using the so-called mismatch negativity (MMN), a negative ERP deflection
      elicited by infrequent irregularities in unattended repetitive auditory
      stimulation. In those studies, lexical processing of spoken stimuli became
      manifest as an enhanced ERP in response to unattended real words, as opposed to
      phonologically matched but meaningless pseudoword stimuli. This lexical ERP
      enhancement was explained by automatic activation of word memory traces realized
      as distributed strongly intra-connected neuronal circuits, whose robustness
      guarantees memory trace activation even in the absence of attention on spoken
      input. Such an account would predict the automatic activation of these memory
      traces upon any presentation of linguistic information, irrespective of the
      presentation modality. As previous lexical MMN studies exclusively used auditory
      stimulation, we here adapted the lexical MMN paradigm to investigate early
      automatic lexical effects in the visual modality. In a visual oddball sequence,
      matched short word and pseudoword stimuli were presented tachistoscopically in
      perifoveal area outside the visual focus of attention, as the subjects' attention
      was concentrated on a concurrent non-linguistic visual dual task in the center of
      the screen. Using EEG, we found a visual analogue of the lexical ERP enhancement
      effect, with unattended written words producing larger brain response amplitudes
      than matched pseudowords, starting at ~100 ms. Furthermore, we also found
      significant visual MMN, reported here for the first time for unattended
      perifoveal lexical stimuli. The data suggest early automatic lexical processing
      of visually presented language which commences rapidly and can take place outside
      the focus of attention. 

PMID- 23950741
TI  - The morphology of midcingulate cortex predicts frontal-midline theta
      neurofeedback success.
AB  - Humans differ in their ability to learn how to control their own brain activity
      by neurofeedback. However, neural mechanisms underlying these inter-individual
      differences, which may determine training success and associated cognitive
      enhancement, are not well-understood. Here, it is asked whether neurofeedback
      success of frontal-midline (fm) theta, an oscillation related to higher cognitive
      functions, could be predicted by the morphology of brain structures known to be
      critically involved in fm-theta generation. Nineteen young, right-handed
      participants underwent magnetic resonance imaging of T1-weighted brain images,
      and took part in an individualized, eight-session neurofeedback training in order
      to learn how to enhance activity in their fm-theta frequency band. Initial
      training success, measured at the second training session, was correlated with
      the final outcome measure. We found that the inferior, superior, and middle
      frontal cortices were not associated with training success. However, volume of
      the midcingulate cortex as well as volume and concentration of the underlying
      white matter structures act as predictor variables for the general responsiveness
      to training. These findings suggest a neuroanatomical foundation for the ability
      to learn to control one's own brain activity. 

PMID- 23950742
TI  - Impaired auditory sampling in dyslexia: further evidence from combined fMRI and
      EEG.
AB  - The aim of the present study was to explore auditory cortical oscillation
      properties in developmental dyslexia. We recorded cortical activity in 17
      dyslexic participants and 15 matched controls using simultaneous EEG and fMRI
      during passive viewing of an audiovisual movie. We compared the distribution of
      brain oscillations in the delta, theta and gamma ranges over left and right
      auditory cortices. In controls, our results are consistent with the hypothesis
      that there is a dominance of gamma oscillations in the left hemisphere and a
      dominance of delta-theta oscillations in the right hemisphere. In dyslexics, we
      did not find such an interaction, but similar oscillations in both hemispheres.
      Thus, our results confirm that the primary cortical disruption in dyslexia lies
      in a lack of hemispheric specialization for gamma oscillations, which might
      disrupt the representation of or the access to phonemic units. 

PMID- 23950743
TI  - Modular reorganization of brain resting state networks and its independent
      validation in Alzheimer's disease patients.
AB  - Previous studies have demonstrated disruption in structural and functional
      connectivity occurring in the Alzheimer's Disease (AD). However, it is not known
      how these disruptions alter brain network reorganization. With the modular
      analysis method of graph theory, and datasets acquired by the resting-state
      functional connectivity MRI (R-fMRI) method, we investigated and compared the
      brain organization patterns between the AD group and the cognitively normal
      control (CN) group. Our main finding is that the largest homotopic module
      (defined as the insula module) in the CN group was broken down to the pieces in
      the AD group. Specifically, it was discovered that the eight pairs of the
      bilateral regions (the opercular part of inferior frontal gyrus, area
      triangularis, insula, putamen, globus pallidus, transverse temporal gyri,
      superior temporal gyrus, and superior temporal pole) of the insula module had
      lost symmetric functional connection properties, and the corresponding gray
      matter concentration (GMC) was significant lower in AD group. We further
      quantified the functional connectivity changes with an index (index A) and
      structural changes with the GMC index in the insula module to demonstrate their
      great potential as AD biomarkers. We further validated these results with six
      additional independent datasets (271 subjects in six groups). Our results
      demonstrated specific underlying structural and functional reorganization from
      young to old, and for diseased subjects. Further, it is suggested that by
      combining the structural GMC analysis and functional modular analysis in the
      insula module, a new biomarker can be developed at the single-subject level. 

PMID- 23950744
TI  - Comparing the Microvascular Specificity of the 3- and 7-T BOLD Response Using ICA
      and Susceptibility-Weighted Imaging.
AB  - In functional MRI it is desirable for the blood-oxygenation level dependent
      (BOLD) signal to be localized to the tissue containing activated neurons rather
      than the veins draining that tissue. This study addresses the dependence of the
      specificity of the BOLD signal - the relative contribution of the BOLD signal
      arising from tissue compared to venous vessels - on magnetic field strength. To
      date, studies of specificity have been based on models or indirect measures of
      BOLD sensitivity such as signal to noise ratio and relaxation rates, and
      assessment has been made in isolated vein and tissue voxels. The consensus has
      been that ultra-high field systems not only significantly increase BOLD
      sensitivity but also specificity, that is, there is a proportionately reduced
      signal contribution from draining veins. Specificity was not quantified in prior
      studies, however, due to the difficulty of establishing a reliable network of
      veins in the activated volume. In this study we use a map of venous vessel
      networks extracted from 7 T high resolution Susceptibility-Weighted Images to
      quantify the relative contributions of micro- and macro-vasculature to functional
      MRI results obtained at 3 and 7 T. High resolution measurements made here
      minimize the contribution of physiological noise and Independent Component
      Analysis (ICA) is used to separate activation from technical, physiological, and
      motion artifacts. ICA also avoids the possibility of timing-dependent bias from
      different micro- and macro-vasculature responses. We find a significant increase
      in the number of activated voxels at 7 T in both the veins and the
      microvasculature - a BOLD sensitivity increase - with the increase in the
      microvasculature being higher. However, the small increase in sensitivity at 7 T
      was not significant. For the experimental conditions of this study, our findings
      do not support the hypothesis of an increased specificity of the BOLD response at
      ultra-high field. 

PMID- 23950746
TI  - A randomized controlled trial with a Canadian electronic pill dispenser used to
      measure and improve medication adherence in patients with schizophrenia.
AB  - OBJECTIVE: Medication adherence is extremely important in preventing relapse and
      lowering symptoms in schizophrenic patients. However, estimates show that nearly
      half of these patients have poor adherence. The Brief Adherence Rating Scale
      (BARS) seems to be the most reliable tool assessing adherence in schizophrenia
      and shows that the antipsychotic adherence ratio (AAR) is about 49.5% in
      schizophrenia. The aim of the study was to test if an electronic pill dispenser
      named DoPill((r)) improved AAR of schizophrenic patients. Furthermore, we
      compared AAR obtained by the DoPill((r)) and the BARS, in order to verify whether
      the DoPill((r)) provides reliable assessment of medication adherence. METHODS:
      The DoPill((r)) is a smart pill dispenser that beeps and flashes at the
      appropriate time of the day. Each of its 28 compartments is covered by a plastic
      lamina that, when taken off, sends a signal to the pharmacist. Patients were
      randomized to the DoPill((r)) or treatment as usual groups for 6 weeks. The BARS
      was used as a reference measure. RESULTS: Forty-six percent of patients were
      deemed to be non-adherent with antipsychotic medication. The mean AAR was 67%
      after 6 weeks. DoPill((r)) recorded better AAR than some of those found in the
      literature and were lower than the BARS estimate we found. CONCLUSION: These
      results suggest that DoPill((r)) is a valid tool that provides more reliable and
      objective data for the clinician about their patient's adherence, than existing
      assessment tools like the BARS. Furthermore, the device may help patients
      successfully manage their medication regimen.

PMID- 23950745
TI  - Comorbid obsessive-compulsive symptoms in schizophrenia: contributions of
      pharmacological and genetic factors.
AB  - A large subgroup of around 25% of schizophrenia patients suffers from obsessive
      compulsive symptoms (OCS) and about 12% fulfill the diagnostic criteria of an
      obsessive-compulsive disorder (OCD). The additional occurrence of OCS is
      associated with high subjective burden of disease, additional neurocognitive
      impairment, poorer social and vocational functioning, greater service utilization
      and high levels of anxiety and depression. Comorbid patients can be assigned to
      heterogeneous subgroups. One hypothesis assumes that second generation
      antipsychotics (SGAs), most importantly clozapine, might aggravate or even induce
      second-onset OCS. Several arguments support this assumption, most importantly the
      observed chronological order of first psychotic manifestation, start of treatment
      with clozapine and onset of OCS. In addition, correlations between OCS-severity
      and dose and serum levels and duration of clozapine treatment hint toward a dose
      dependent side effect. It has been hypothesized that genetic risk-factors dispose
      patients with schizophrenia to develop OCS. One study in a South Korean sample
      reported associations with polymorphisms in the gene SLC1A1 (solute carrier
      family 1A1) and SGA-induced OCS. However, this finding could not be replicated in
      European patients. Preliminary results also suggest an involvement of
      polymorphisms in the BDNF gene (brain-derived neurotrophic factor) and an
      interaction between markers of SLC1A1 and the gene DLGAP3 (disc large associated
      protein 3) as well as GRIN2B (N-methyl-D-aspartate receptor subunit 2B). Further
      research of well-defined samples, in particular studies investigating possible
      interactions of genetic risk-constellations and pharmacodynamic properties, are
      needed to clarify the assumed development of SGA-induced OCS. Results might
      improve pathogenic concepts and facilitate the definition of at risk populations,
      early detection and monitoring of OCS as well as multimodal therapeutic
      interventions. 

PMID- 23950748
TI  - The Role of Study and Work in Cannabis Use and Dependence Trajectories among
      Young Adult Frequent Cannabis Users.
AB  - Life course theory considers events in study and work as potential turning points
      in deviance, including illicit drug use. This qualitative study explores the role
      of occupational life in cannabis use and dependence in young adults. Two and
      three years after the initial structured interview, 47 at baseline frequent
      cannabis users were interviewed in-depth about the dynamics underlying changes in
      their cannabis use and dependence. Overall, cannabis use and dependence declined,
      including interviewees who quit using cannabis completely, in particular with
      students, both during their study and after they got employed. Life course theory
      appeared to be a useful framework to explore how and why occupational life is
      related to cannabis use and dependence over time. Our study showed that life
      events in this realm are rather common in young adults and can have a strong
      impact on cannabis use. While sometimes changes in use are temporary, turning
      points can evolve from changes in educational and employment situations; an
      effect that seems to be related to the consequences of these changes in terms of
      amount of leisure time and agency (i.e., feelings of being in control). 

PMID- 23950747
TI  - Immune infiltrates as predictive markers of survival in pancreatic cancer
      patients.
AB  - Pancreatic cancer is a devastating disease with dismal prognosis. The tumor
      microenvironment is composed by multiple cell types, molecular factors, and
      extracellular matrix forming a strong desmoplastic reaction, which is a hallmark
      of the disease. A complex cross-talk between tumor cells and the stroma exists
      with reciprocal influence that dictates tumor progression and ultimately the
      clinical outcome. In this context, tumor infiltrating immune cells through
      secretion of chemokine and cytokines exert an important regulatory role. Here we
      review the correlation between the immune infiltrates, evaluated on tumor samples
      of pancreatic cancer patients underwent surgical resection, and disease free
      and/or overall survival after surgery. Specifically, we focus on tumor
      infiltrating lymphocytes (TILs), mast cells (MCs) and macrophages that all
      contribute to a Th2-type inflammatory and immunosuppressive microenvironment. In
      these patients tumor immune infiltrates not only do not contribute to disease
      eradication but rather the features of Th2-type inflammation and
      immunosuppression is significantly associated with more rapid disease progression
      and reduced survival. 

PMID- 23950749
TI  - I speak fast when I move fast: the speed of illusory self-motion (vection)
      modulates the speed of utterances.
AB  - Speed of utterance is an important factor in smooth and efficient conversation.
      We report a technique to increase utterance speed and that might improve a
      speaker's impression and information efficiency in conversation. We used a visual
      display consisting of optic flows in a large visual field that induced
      participants' illusory self-motion perception (vection). The speed of vection
      corresponded to the speed of the optic flows. Using this method, we investigated
      whether vection speed affects utterance speed. We presented fast- and slow-moving
      optic flow stimuli while dynamically swapping random dots presented to
      participants, during which time the participants were asked to talk for 2 min.
      Results revealed that the utterance speed was significantly faster in the fast
      optic flow condition. Our method could be a stepping stone for establishing a
      technique of modulating speech speed effectively. 

PMID- 23950751
TI  - Individual differences in chemotherapy-induced anticipatory nausea.
AB  - Anticipatory Nausea (AN) is a severe side effect of chemotherapy that can lead
      cancer patients to discontinue their treatment. This kind of nausea is usually
      elicited by the re-exposure of the patients to the clinical context they need to
      attend to be treated. There has been considerable agreement that AN represents a
      paradigmatic example of Pavlovian conditioning, and within this framework,
      several behavioral interventions have been proposed in order to prevent this
      phenomenon. However, some studies have questioned the validity of the Pavlovian
      approach, suggesting that CS-US associations are neither necessary nor sufficient
      for AN to occur. The data and the alternative theories behind such criticisms are
      discussed. Additionally, it is suggested that animal models of AN could be
      enriched by taking into account rats' individual differences. 

PMID- 23950752
TI  - The proximate unit in Chinese handwritten character production.
AB  - In spoken word production, a proximate unit is the first phonological unit at the
      sublexical level that is selectable for production (O'Seaghdha et al., 2010). The
      present study investigated whether the proximate unit in Chinese handwritten
      character production is the stroke, the radical, or something in between. A
      written version of the form preparation task was adopted. Chinese participants
      learned sets of two-character words, later were cued with the first character of
      each word, and had to write down the second character (the target). Response
      times were measured from the onset of a cue character to the onset of a written
      response. In Experiment 1, the target characters within a block shared
      (homogeneous) or did not share (heterogeneous) the first stroke. In Experiment 2,
      the first two strokes were shared in the homogeneous blocks. Response times in
      the homogeneous blocks and in the heterogeneous blocks were comparable in both
      experiments (Experiment 1: 687 vs. 684 ms, Experiment 2: 717 vs. 716). In
      Experiment 3 and 4, the target characters within a block shared or did not share
      the first radical. Response times in the homogeneous blocks were significantly
      faster than those in the heterogeneous blocks (Experiment 3: 685 vs. 704,
      Experiment 4: 594 vs. 650). In Experiment 5 and 6, the shared component was a
      Gestalt-like form that is more than a stroke, constitutes a portion of the target
      character, can be a stand-alone character itself, can be a radical of another
      character but is not a radical of the target character (e.g., +/- in , , , ;
      called a logographeme). Response times in the homogeneous blocks were
      significantly faster than those in the heterogeneous blocks (Experiment 5: 576
      vs. 625, Experiment 6: 586 vs. 620). These results suggest a model of Chinese
      handwritten character production in which the stroke is not a functional unit,
      the radical plays the role of a morpheme, and the logographeme is the proximate
      unit. 

PMID- 23950753
TI  - Early infant's use of visual feedback in voluntary reaching for a spatial target.
AB  - Capacity of using visual feedback by infants at the age of reaching onset has
      been controversial. In this investigation we assessed movement kinematics in the
      task of reaching for a toy in 5-month-olds, comparing movements performed with
      the preferred arm under full vision versus visual occlusion. That comparison was
      made in consecutive periods of visual occlusion. Analysis of results revealed
      that visual occlusion led to decreased straightness of arm displacement toward
      the toy as compared to full vision. Longer periods of occlusion did not augment
      that effect. These results offer preliminary evidence for use of visual feedback
      early in infants' reaching development. Reconciliation of previous and current
      findings is made by proposing a hybrid mode of feedback processing for manual
      control reweighting the roles of vision and proprioception as a function of
      availability of environmental information. 

PMID- 23950750
TI  - The efference cascade, consciousness, and its self: naturalizing the first person
      pivot of action control.
AB  - The 20 billion neurons of the neocortex have a mere hundred thousand motor
      neurons by which to express cortical contents in overt behavior. Implemented
      through a staggered cortical "efference cascade" originating in the descending
      axons of layer five pyramidal cells throughout the neocortical expanse, this
      steep convergence accomplishes final integration for action of cortical
      information through a system of interconnected subcortical way stations. Coherent
      and effective action control requires the inclusion of a continually updated
      joint "global best estimate" of current sensory, motivational, and motor
      circumstances in this process. I have previously proposed that this running best
      estimate is extracted from cortical probabilistic preliminaries by a subcortical
      neural "reality model" implementing our conscious sensory phenomenology. As such
      it must exhibit first person perspectival organization, suggested to derive from
      formating requirements of the brain's subsystem for gaze control, with the
      superior colliculus at its base. Gaze movements provide the leading edge of
      behavior by capturing targets of engagement prior to contact. The rotation-based
      geometry of directional gaze movements places their implicit origin inside the
      head, a location recoverable by cortical probabilistic source reconstruction from
      the rampant primary sensory variance generated by the incessant play of
      collicularly triggered gaze movements. At the interface between cortex and
      colliculus lies the dorsal pulvinar. Its unique long-range inhibitory circuitry
      may precipitate the brain's global best estimate of its momentary circumstances
      through multiple constraint satisfaction across its afferents from numerous
      cortical areas and colliculus. As phenomenal content of our sensory awareness,
      such a global best estimate would exhibit perspectival organization centered on a
      purely implicit first person origin, inherently incapable of appearing as a
      phenomenal content of the sensory space it serves. 

PMID- 23950754
TI  - The impact of emotion on numerosity estimation.
AB  - Both time and numerosity can be represented continuously as analog properties
      whose discrimination conforms to Weber's Law, suggesting that the two properties
      may be represented similarly. Recent research suggests that the representation of
      time is influenced by the presence of emotional stimuli. If time and numerosity
      share a common cognitive representation, it follows that a similar relationship
      may exist between emotional stimuli and the representation of numerosity. Here,
      we provide evidence that emotional stimuli significantly affect humans'
      estimation of visual numerosity. During a numerical bisection task, enumeration
      of emotional stimuli (angry faces) was more accurate compared to enumeration of
      neutrally valenced stimuli (neutral faces), demonstrating that emotional stimuli
      affect humans' visual representation of numerosity as previously demonstrated for
      time. These results inform and broaden our understanding of the effect of
      negative emotional stimuli on psychophysical discriminations of quantity. 

PMID- 23950755
TI  - Administration of neuropsychological tests using interactive voice response
      technology in the elderly: validation and limitations.
AB  - Interactive voice response (IVR) systems are computer programs, which interact
      with people to provide a number of services from business to health care. We
      examined the ability of an IVR system to administer and score a verbal fluency
      task (fruits) and the digit span forward and backward in 158 community dwelling
      people aged between 65 and 92 years of age (full scale IQ of 68-134). Only six
      participants could not complete all tasks mostly due to early technical problems
      in the study. Participants were also administered the Wechsler Intelligence Scale
      fourth edition (WAIS-IV) and Wechsler Memory Scale fourth edition subtests. The
      IVR system correctly recognized 90% of the fruits in the verbal fluency task and
      93-95% of the number sequences in the digit span. The IVR system typically
      underestimated the performance of participants because of voice recognition
      errors. In the digit span, these errors led to the erroneous discontinuation of
      the test: however the correlation between IVR scoring and clinical scoring was
      still high (93-95%). The correlation between the IVR verbal fluency and the WAIS
      IV Similarities subtest was 0.31. The correlation between the IVR digit span
      forward and backward and the in-person administration was 0.46. We discuss how
      valid and useful IVR systems are for neuropsychological testing in the elderly. 

PMID- 23950756
TI  - IGF-I, IGF-II, and Insulin Stimulate Different Gene Expression Responses through
      Binding to the IGF-I Receptor.
AB  - Insulin and the insulin-like growth factors (IGF)-I and -II are closely related
      peptides important for regulation of metabolism, growth, differentiation, and
      development. The IGFs exert their main effects through the IGF-I receptor.
      Although the insulin receptor is the main physiological receptor for insulin,
      this peptide hormone can also bind at higher concentrations to the IGF-I receptor
      and exert effects through it. We used microarray gene expression profiling to
      investigate the gene expression regulated by IGF-I, IGF-II, and insulin after
      stimulation of the IGF-I receptor. Fibroblasts from mice, knockout for IGF-II and
      the IGF-II/cation-independent mannose-6-phosphate receptor, and expressing
      functional IGF-I but no insulin receptors, were stimulated for 4 h with
      equipotent saturating concentrations of insulin, IGF-I, and IGF-II. Each ligand
      specifically regulated a group of transcripts that was not regulated by the other
      two ligands. Many of the functions and pathways these regulated genes were
      involved in, were consistent with the known biological effects of these ligands.
      The differences in gene expression might therefore account for some of the
      different biological effects of insulin, IGF-I, and IGF-II. This work adds to the
      evidence that not only the affinity of a ligand determines its biological
      response, but also its nature, even through the same receptor. 

PMID- 23950757
TI  - A Temporal Model of Human IgE and IgG Antibody Function.
AB  - The diversity of the human antibody repertoire that is generated by V(D)J gene
      rearrangement is extended by nine constant region genes that give antibodies
      their complex array of effector functions. The application of high throughput
      sequencing to the study of V(D)J gene rearrangements has led to significant
      recent advances in our understanding of the antigen-binding repertoire. In
      contrast, our understanding of antibody function has changed little, and mystery
      still surrounds the existence of four distinctive IgG subclasses. Recent
      observations from murine models and from human studies of VDJ somatic point
      mutations suggest that the timing of emergence of cells from the germinal center
      may vary as a consequence of class switching. This should lead to predictable
      differences in affinity between isotypes. These differences, and varying
      abilities of the isotypes to fix complement and bind FcRs, could help coordinate
      the humoral defenses over the time course of a response. We therefore propose a
      Temporal Model of human IgE and IgG function in which early emergence of IgE
      sensitizes sentinel mast cells while switching to IgG3 recruits FcgammaR-mediated
      functions to the early response. IgG1 then emerges as the major effector of
      antigen clearance, and subsequently IgG2 competes with IgG1 to produce immune
      complexes that slow the inflammatory drive. Persisting antigen may finally
      stimulate high affinity IgG4 that outcompetes other isotypes and can terminate
      IgG1/FcgammaR-mediated activation via the inhibitory FcgammaRIIB. In this way,
      IgG antibodies of different subclasses, at different concentrations and with
      sometimes opposing functions deliver cohesive, protective immune function. 

PMID- 23950758
TI  - Evolution of the selfing syndrome in Ipomoea.
AB  - Plants that are highly selfing typically exhibit a suite of morphological traits
      termed a "selfing syndrome," including reduced corollas and reproductive
      structures, loss of corolla pigmentation, little anther-stigma separation, and a
      lower pollen/ovule (P/O) ratio. While it is typically assumed that these changes
      are adaptive, few attempts have been made to determine whether they result from
      the operation of natural selection or genetic drift. In the southeastern United
      States, Ipomoea lacunosa has evolved a typical selfing syndrome compared to its
      close relative, Ipomoea cordatotriloba. Microsatellite markers confirmed that
      selfing rates are substantially higher in I. lacunosa. Furthermore, using a
      standard QST - FST comparison, we evaluated the relative importance of selection
      and drift in the evolution of selfing syndrome traits in I. lacunosa. The
      analysis demonstrated that natural selection is responsible for the evolution of
      reduced corolla size, anther-stigma distance, and style length in this species.
      By contrast, leaf characteristics unrelated to selfing were found to have
      diverged largely by genetic drift. Our study provides one of the first
      confirmations that natural selection drives the evolution of selfing-syndrome
      traits. 

PMID- 23950759
TI  - Pyrophosphate levels strongly influence ascorbate and starch content in tomato
      fruit.
AB  - Ascorbate (vitamin C) deficiency leads to low immunity, scurvy, and other human
      diseases and is therefore a global health problem. Given that plants are major
      ascorbate sources for humans, biofortification of this vitamin in our foodstuffs
      is of considerable importance. Ascorbate is synthetized by a number of
      alternative pathways: (i) from the glycolytic intermediates D-glucose-6P (the key
      intermediates are GDP-D-mannose and L-galactose), (ii) from the breakdown of the
      cell wall polymer pectin which uses the methyl ester of D-galacturonic acid as
      precursor, and (iii) from myo-inositol as precursor via myo-inositol oxygenase.
      We report here the engineering of fruit-specific overexpression of a bacterial
      pyrophosphatase, which hydrolyzes the inorganic pyrophosphate (PPi) to
      orthophosphate (Pi). This strategy resulted in increased vitamin C levels up to
      2.5-fold in ripe fruit as well as increasing in the major sugars, sucrose, and
      glucose, yet decreasing the level of starch. When considered together, these
      finding indicate an intimate linkage between ascorbate and sugar biosynthesis in
      plants. Moreover, the combined data reveal the importance of PPi metabolism in
      tomato fruit metabolism and development. 

PMID- 23950761
TI  - A HETEROSCEDASTIC METHOD FOR COMPARING REGRESSION LINES AT SPECIFIED DESIGN
      POINTS WHEN USING A ROBUST REGRESSION ESTIMATOR.
AB  - It is well known that the ordinary least squares (OLS) regression estimator is
      not robust. Many robust regression estimators have been proposed and inferential
      methods based on these estimators have been derived. However, for two independent
      groups, let thetaj (X) be some conditional measure of location for the jth group,
      given X, based on some robust regression estimator. An issue that has not been
      addressed is computing a 1 - alpha confidence interval for theta1(X) - theta2(X)
      in a manner that allows both within group and between group hetereoscedasticity.
      The paper reports the finite sample properties of a simple method for
      accomplishing this goal. Simulations indicate that, in terms of controlling the
      probability of a Type I error, the method performs very well for a wide range of
      situations, even with a relatively small sample size. In principle, any robust
      regression estimator can be used. The simulations are focused primarily on the
      Theil-Sen estimator, but some results using Yohai's MM-estimator, as well as the
      Koenker and Bassett quantile regression estimator, are noted. Data from the Well
      Elderly II study, dealing with measures of meaningful activity using the cortisol
      awakening response as a covariate, are used to illustrate that the choice between
      an extant method based on a nonparametric regression estimator, and the method
      suggested here, can make a practical difference.

PMID- 23950760
TI  - Human migration, diversity and disease association: a convergent role of
      established and emerging DNA markers.
AB  - With the gradual development of intelligence, human got curious to know his
      origin and evolutionary background. Historical statements and anthropological
      findings were his primary tool for solving the puzzles of his own origin, until
      came the golden era of molecular markers which took no time to prove it's
      excellence in unveiling answers to the questions regarding the migration pattern
      of human across different geographical regions. As a bonus these markers proved
      very much beneficial in solving criminal offenses and in understanding the
      etiology of many dreaded diseases and to design their prevention. In this review,
      we have aimed to throw light on some of the promising molecular markers which are
      very much in application now-a-days for not only understanding the evolutionary
      background and ancient migratory routes of humans but also in the field of
      forensics and human health. 

PMID- 23950762
TI  - Comparison of regenerated and non-regenerated oxidized cellulose hemostatic
      agents.
AB  - BACKGROUND: Oxidized cellulose is a well known and widely used surgical hemostat.
      It is available in many forms, but manufactured using either a nonregenerated or
      regenerated process. OBJECTIVE: This study compares the fiber structure, pH in
      solution, bactericidal effectiveness, and hemostatic effectiveness of an oxidized
      nonregenerated cellulose (ONRC; Traumastem(r)) and an oxidized regenerated
      cellulose (ORC; Surgicel(r) Original). METHODS: In vitro, fiber structures were
      compared using scanning electron microscopy, pH of phosphate buffer solution
      (PBS) and human plasma were measured after each cellulose was submerged, and
      bactericidal effect was measured by plating each cellulose with four bacteria. In
      vivo, time to hemostasis and hemostatic success were compared using a general
      surgery nonheparinized porcine liver abrasion model and a peripheral vascular
      surgery heparinized leporine femoral vessel bleeding model. RESULTS:
      Ultrastructure of ONRC fiber is frayed, while ORC is smooth. ORC pH is
      statistically more acidic than ONRC in PBS, but equal in plasma. No difference in
      bactericidal effectiveness was observed. In vivo, ONRC provided superior time to
      hemostasis relative to ORC (211.2 vs 384.6 s, N = 60/group) in the general
      surgery model; and superior hemostatic success relative to ORC at 30 (60 vs. 15
      %; OR: 13.5; 95 % CI: 3.72-49.1, N = 40/group), 60 (85 vs. 37.5 %; OR: 12.3; 95 %
      CI: 3.66-41.6), and 90 s (97.5 vs 70.0 %; OR: 21.1, 95 % CI: 2.28-195.9) in the
      peripheral vascular model. CONCLUSION: ONRC provides superior hemostasis and
      equivalent bactericidal effectiveness relative to ORC, which is likely due to its
      fiber structure than acidity.

PMID- 23950763
TI  - Spiked Dirichlet Process Priors for Gaussian Process Models.
AB  - We expand a framework for Bayesian variable selection for Gaussian process (GP)
      models by employing spiked Dirichlet process (DP) prior constructions over set
      partitions containing covariates. Our approach results in a nonparametric
      treatment of the distribution of the covariance parameters of the GP covariance
      matrix that in turn induces a clustering of the covariates. We evaluate two prior
      constructions: the first one employs a mixture of a point-mass and a continuous
      distribution as the centering distribution for the DP prior, therefore,
      clustering all covariates. The second one employs a mixture of a spike and a DP
      prior with a continuous distribution as the centering distribution, which induces
      clustering of the selected covariates only. DP models borrow information across
      covariates through model-based clustering. Our simulation results, in particular,
      show a reduction in posterior sampling variability and, in turn, enhanced
      prediction performances. In our model formulations, we accomplish posterior
      inference by employing novel combinations and extensions of existing algorithms
      for inference with DP prior models and compare performances under the two prior
      constructions.

PMID- 23950764
TI  - Fluctuating Hydrodynamics Approach for the Simulation of Nanoparticle Brownian
      Motion in a Newtonian Fluid.
AB  - The Brownian motion of a nanoparticle in an incompressible Newtonian fluid
      (quiescent or fully developed Poiseuille flow) has been investigated with an
      arbitrary Lagrangian-Eulerian based finite element method. Results for the motion
      in a compressible fluid medium are estimated. Thermal fluctuations from the fluid
      are implemented using a fluctuating hydrodynamics approach. The instantaneous
      flow around the particle and the particle motion are fully resolved. Carriers of
      two different sizes with three different densities have been investigated (nearly
      neutrally buoyant). The numerical results show that (a) the calculated
      temperature of the nearly neutrally buoyant Brownian particle in a quiescent
      fluid satisfies the equipartition theorem; (b) the translational and rotational
      decay of the velocity autocorrelation functions result in algebraic tails, over
      long time; (c) the translational and rotational mean square displacements of the
      particle obeys Stokes-Einstein and Stokes-Einstein-Debye relations, respectively.
      Larger the particle, longer the time taken to attain this limit; and (d) the
      parallel and perpendicular diffusivities of the particle closer to the wall are
      consistent with the analytical results, where available.

PMID- 23950765
TI  - Introduction to the fractality principle of consciousness and the sentyon
      postulate.
AB  - Recently, consciousness research has gained much attention. Indeed, the question
      at stake is significant: why is the brain not just a computing device, but
      generates a perception from within? Ambitious endeavors trying to simulate the
      entire human brain assume that the algorithm will do the trick: as soon as we
      assemble the brain in a computer and increase the number of operations per time,
      consciousness will emerge by itself. I disagree with this simplistic
      representation. My argument emerges from the "atomism paradox": the irreducible
      space of the consciously perceived world, the endospace is incompatible with the
      reducible and decomposable architecture of the brain or a computer. I will first
      discuss the fundamental challenges in current consciousness models and then
      propose a new model based on the fractality principle: "the whole is in each of
      its parts". This new model copes with the atomism paradox by implementing an
      iterative mapping of information from higher order brain structures to smaller
      scales on the cellular and molecular level, which I will refer to as
      "fractalization". This information fractalization gives rise to a new form of
      matter that is conscious ("bright matter"). Bright matter is composed of
      conscious particles or units named "sentyons". The internal fractality of these
      sentyons will close a loop (the "psychic loop") in a recurrent fractal neural
      network (RFNN) that allows for continuous and complete information transformation
      and sharing between higher order brain structures and the endpoint substrate of
      consciousness at the molecular level.

PMID- 23950766
TI  - Spiked Dirichlet Process Prior for Bayesian Multiple Hypothesis Testing in Random
      Effects Models.
AB  - We propose a Bayesian method for multiple hypothesis testing in random effects
      models that uses Dirichlet process (DP) priors for a nonparametric treatment of
      the random effects distribution. We consider a general model formulation which
      accommodates a variety of multiple treatment conditions. A key feature of our
      method is the use of a product of spiked distributions, i.e., mixtures of a point
      mass and continuous distributions, as the centering distribution for the DP
      prior. Adopting these spiked centering priors readily accommodates sharp null
      hypotheses and allows for the estimation of the posterior probabilities of such
      hypotheses. Dirichlet process mixture models naturally borrow information across
      objects through model-based clustering while inference on single hypotheses
      averages over clustering uncertainty. We demonstrate via a simulation study that
      our method yields increased sensitivity in multiple hypothesis testing and
      produces a lower proportion of false discoveries than other competitive methods.
      While our modeling framework is general, here we present an application in the
      context of gene expression from microarray experiments. In our application, the
      modeling framework allows simultaneous inference on the parameters governing
      differential expression and inference on the clustering of genes. We use
      experimental data on the transcriptional response to oxidative stress in mouse
      heart muscle and compare the results from our procedure with existing
      nonparametric Bayesian methods that provide only a ranking of the genes by their
      evidence for differential expression.

PMID- 23950785
TI  - Identifying the world's most climate change vulnerable species: a systematic
      trait-based assessment of all birds, amphibians and corals.
AB  - Climate change will have far-reaching impacts on biodiversity, including
      increasing extinction rates. Current approaches to quantifying such impacts focus
      on measuring exposure to climatic change and largely ignore the biological
      differences between species that may significantly increase or reduce their
      vulnerability. To address this, we present a framework for assessing three
      dimensions of climate change vulnerability, namely sensitivity, exposure and
      adaptive capacity; this draws on species' biological traits and their modeled
      exposure to projected climatic changes. In the largest such assessment to date,
      we applied this approach to each of the world's birds, amphibians and corals
      (16,857 species). The resulting assessments identify the species with greatest
      relative vulnerability to climate change and the geographic areas in which they
      are concentrated, including the Amazon basin for amphibians and birds, and the
      central Indo-west Pacific (Coral Triangle) for corals. We found that high
      concentration areas for species with traits conferring highest sensitivity and
      lowest adaptive capacity differ from those of highly exposed species, and we
      identify areas where exposure-based assessments alone may over or under-estimate
      climate change impacts. We found that 608-851 bird (6-9%), 670-933 amphibian (11
      15%), and 47-73 coral species (6-9%) are both highly climate change vulnerable
      and already threatened with extinction on the IUCN Red List. The remaining highly
      climate change vulnerable species represent new priorities for conservation.
      Fewer species are highly climate change vulnerable under lower IPCC SRES
      emissions scenarios, indicating that reducing greenhouse emissions will reduce
      climate change driven extinctions. Our study answers the growing call for a more
      biologically and ecologically inclusive approach to assessing climate change
      vulnerability. By facilitating independent assessment of the three dimensions of
      climate change vulnerability, our approach can be used to devise species and area
      specific conservation interventions and indices. The priorities we identify will
      strengthen global strategies to mitigate climate change impacts.

PMID- 23950786
TI  - Sexual behavior and condom use among gay men, female sex workers, and their
      customers: evidence from South Korea.
AB  - BACKGROUND: Despite the significance for sexually transmitted diseases (STD)
      control in East Asia, few studies have examined the relationship between high
      risk sexual behavior and condom use. We investigated how three sexually
      vulnerable groups for STDs show differences in condom use behaviors (CUBs)
      depending on their STD infection. METHODS: The source of data came from the
      National Survey for STD Prevalence Rate and Sexual Behavior of the High-Risk
      Sexual Community. The effects of behavioral determinants on CUBs were estimated
      by using path analysis models. An 11-item questionnaire assessing subjects'
      health risk behaviors, sexual beliefs, sexual risk behaviors, and condom use.
      RESULTS: Condom use was higher for men who have sex with men (MSM; n  =  108)
      when they were bisexuals and had high self-efficacy, for Johns (Johns; n  =  118)
      when they had experience of STD infection, and for female sex workers (FSWs; n  =
      1,083) when they had high self-efficacy, did not engage in drunken sex, and were
      anxious about infection. Regardless of whether they were infected with STDs, FSWs
      always used condom when they had high sexual beliefs. On the contrary, Johns
      exhibited a negative relationship between sexual risk behavior and condom use
      when they had experience of STD infection. The variable commonly significant to
      all three groups was the number of sex partners; but it exhibited a positive
      relationship with MSMs and Johns, and a negative one with FSWs. CONCLUSIONS: CUBs
      were related to sexual beliefs as well as sexual risk behavior. At the same time,
      the experience of STD infection mediated the relationship between the two.
      Therefore, we need to draw social attention to promote safer sex among STD
      vulnerable groups.

PMID- 23950787
TI  - Discrete pattern of burst stimulation in the ventrobasal thalamus for anti
      nociception.
AB  - The thalamus has been proposed to play a role in sensory modulation via switching
      between tonic and burst dual firing of individual neurons. Of the two firing
      modes, altered burst firing has been repeatedly implicated with pathological pain
      conditions, which suggests that maintaining a certain form of thalamic burst
      could be crucial for controlling pain. However, specific elements of burst firing
      that may contribute to pain control have not yet been actively investigated.
      Utilizing the deep brain stimulation (DBS) technique, we explored the effects of
      bursting properties in pain control by electrically stimulating the ventrobasal
      (VB) thalamus in forms of burst patterned to test different aspects of bursts
      during the formalin induced nociception in mice. Our results demonstrated that
      electrical stimulations mimicking specific burst firing properties are important
      in producing an anti-nociceptive effect and found that the <= 3 ms interval
      between burst pluses (intra-burst-interval: IntraBI) and >= 3 pulses per burst
      were required to reliably reduce formalin induced nociceptive responses in mice.
      Periodicity of IntraBI was also suggested to contribute to anti-nociception to a
      limited extent.

PMID- 23950788
TI  - Comparative genome analysis and phylogenetic relationship of order Liliales
      insight from the complete plastid genome sequences of two Lilies (Lilium
      longiflorum and Alstroemeria aurea).
AB  - Monocots are one of the most diverse, successful and economically important
      clades of angiosperms. We attempt to analyse the complete plastid genome
      sequences of two lilies and their lengths were 152,793bp in Lilium longiflorum
      (Liliaceae) and 155,510bp in Alstroemeria aurea (Alstroemeriaceae). Phylogenetic
      analyses were performed for 28 taxa including major lineages of monocots using
      the sequences of 79 plastid genes for clarifying the phylogenetic relationship of
      the order Liliales. The sister relationship of Liliales and Asparagales
      commelinids was improved with high resolution. Comparative analyses of inter
      familial and inter-specific sequence variation were also carried out among three
      families of Liliaceae, Smilacaceae, and Alstroemeriaceae, and between two Lilium
      species of L. longflorum and L. superbum. Gene content and order were conserved
      in the order Liliales except infA loss in Smilax and Alstroemeria. IR boundaries
      were similar in IRa, however, IRb showed different extension patterns as JLB of
      Smilax and JSB in Alstroemeria. Ka/Ks ratio was high in matK among the pair-wise
      comparison of three families and the most variable genes were psaJ, ycf1, rpl32,
      rpl22, matK, and ccsA among the three families and rps15, rpoA, matK, and ndhF
      between Lilium.

PMID- 23950789
TI  - Improving transferability of introduced species' distribution models: new tools
      to forecast the spread of a highly invasive seaweed.
AB  - The utility of species distribution models for applications in invasion and
      global change biology is critically dependent on their transferability between
      regions or points in time, respectively. We introduce two methods that aim to
      improve the transferability of presence-only models: density-based occurrence
      thinning and performance-based predictor selection. We evaluate the effect of
      these methods along with the impact of the choice of model complexity and
      geographic background on the transferability of a species distribution model
      between geographic regions. Our multifactorial experiment focuses on the
      notorious invasive seaweed Caulerpa cylindracea (previously Caulerpa racemosa
      var. cylindracea) and uses Maxent, a commonly used presence-only modeling
      technique. We show that model transferability is markedly improved by appropriate
      predictor selection, with occurrence thinning, model complexity and background
      choice having relatively minor effects. The data shows that, if available,
      occurrence records from the native and invaded regions should be combined as this
      leads to models with high predictive power while reducing the sensitivity to
      choices made in the modeling process. The inferred distribution model of Caulerpa
      cylindracea shows the potential for this species to further spread along the
      coasts of Western Europe, western Africa and the south coast of Australia.

PMID- 23950841
TI  - Tagging of genomic STAT3 and STAT1 with fluorescent proteins and insertion of a
      luciferase reporter in the cyclin D1 gene provides a modified A549 cell line to
      screen for selective STAT3 inhibitors.
AB  - Signal transducer and activator of transcription 3 (STAT3) is an oncogenic
      protein that is constitutively activated in numerous cancer cell lines and human
      cancers. Another STAT family member, STAT1, possesses cancer-inhibitory
      properties and can promote apoptosis in tumor cells upon activation. To better
      characterize these important cancer related genes, we tagged STAT3 and STAT1 loci
      with fluorescent protein (FP) sequences (RFP and GFP respectively) by targeted
      integration via zinc finger nuclease (ZFN)--mediated homologous recombination in
      A549 cells that express aberrantly activated STAT3. We inserted the FP transgenes
      at the N-terminus of the STAT3 locus and at the C-terminus of the STAT1 locus.
      The integration resulted in endogenous expression of fluorescent STAT3 and STAT1
      chimeric fusion proteins. When stimulated with IL-6 or IFN-gamma, the cells
      showed robust nuclear translocation of RFP-STAT3 or STAT1-GFP, respectively. Pre
      incubation of cells with a known specific STAT3 inhibitor showed that IFN-gamma
      induced translocation of STAT1-GFP was not impaired. STAT3 activates multiple
      downstream targets such as genes involved in cell cycle progression - e.g. cyclin
      D1. To detect changes in expression of endogenous cyclin D1, we used ZFN
      technology to insert a secreted luciferase reporter behind the cyclin D1 promoter
      and separated the luciferase and cyclin D1 coding regions by a 2A sequence to
      induce a translational skip. The luciferase insertion was made in the RFP
      STAT3/STAT1-GFP cell line to have all three reporters in a single cell line.
      Addition of a STAT3 inhibitor led to suppression of cyclin D1 promoter activity
      and cell growth arrest. The triple-modified cell line provides a simple and
      convenient method for high-content screening and pre-clinical testing of
      potential STAT3 inhibitors in live cells while ensuring that the STAT1 pathway is
      not affected. This approach of reporting endogenous gene activities using ZFN
      technology could be applied to other cancer targets.

PMID- 23950843
TI  - Genome wide analysis of the apple MYB transcription factor family allows the
      identification of MdoMYB121 gene confering abiotic stress tolerance in plants.
AB  - The MYB proteins comprise one of the largest families of transcription factors
      (TFs) in plants. Although several MYB genes have been characterized to play roles
      in secondary metabolism, the MYB family has not yet been identified in apple. In
      this study, 229 apple MYB genes were identified through a genome-wide analysis
      and divided into 45 subgroups. A computational analysis was conducted using the
      apple genomic database to yield a complete overview of the MYB family, including
      the intron-exon organizations, the sequence features of the MYB DNA-binding
      domains, the carboxy-terminal motifs, and the chromosomal locations.
      Subsequently, the expression of 18 MYB genes, including 12 were chosen from
      stress-related subgroups, while another 6 ones from other subgroups, in response
      to various abiotic stresses was examined. It was found that several of these MYB
      genes, particularly MdoMYB121, were induced by multiple stresses. The MdoMYB121
      was then further functionally characterized. Its predicted protein was found to
      be localized in the nucleus. A transgenic analysis indicated that the
      overexpression of the MdoMYB121 gene remarkably enhanced the tolerance to high
      salinity, drought, and cold stresses in transgenic tomato and apple plants. Our
      results indicate that the MYB genes are highly conserved in plant species and
      that MdoMYB121 can be used as a target gene in genetic engineering approaches to
      improve the tolerance of plants to multiple abiotic stresses. 

PMID- 23950842
TI  - Cytosolic phospholipase A(2)alpha and eicosanoids regulate expression of genes in
      macrophages involved in host defense and inflammation.
AB  - The role of Group IVA cytosolic phospholipase A2 (cPLA2alpha) activation in
      regulating macrophage transcriptional responses to Candida albicans infection was
      investigated. cPLA2alpha releases arachidonic acid for the production of
      eicosanoids. In mouse resident peritoneal macrophages, prostacyclin,
      prostaglandin E2 and leukotriene C4 were produced within minutes of C. albicans
      addition before cyclooxygenase 2 expression. The production of TNFalpha was lower
      in C. albicans-stimulated cPLA2alpha(+/+) than cPLA2alpha(-/-) macrophages due to
      an autocrine effect of prostaglandins that increased cAMP to a greater extent in
      cPLA2alpha(+/+) than cPLA2alpha(-/-) macrophages. For global insight,
      differential gene expression in C. albicans-stimulated cPLA2alpha(+/+) and
      cPLA2alpha(-/-) macrophages (3 h) was compared by microarray. cPLA2alpha(+/+)
      macrophages expressed 86 genes at lower levels and 181 genes at higher levels
      than cPLA2alpha(-/-) macrophages (>=2-fold, p<0.05). Several pro-inflammatory
      genes were expressed at lower levels (Tnfalpha, Cx3cl1, Cd40, Ccl5, Csf1, Edn1,
      CxCr7, Irf1, Irf4, Akna, Ifngamma, several IFNgamma-inducible GTPases). Genes
      that dampen inflammation (Socs3, Il10, Crem, Stat3, Thbd, Thbs1, Abca1) and genes
      involved in host defense (Gja1, Csf3, Trem1, Hdc) were expressed at higher levels
      in cPLA2alpha(+/+) macrophages. Representative genes expressed lower in
      cPLA2alpha(+/+) macrophages (Tnfalpha, Csf1) were increased by treatment with a
      prostacyclin receptor antagonist and protein kinase A inhibitor, whereas genes
      expressed at higher levels (Crem, Nr4a2, Il10, Csf3) were suppressed. The results
      suggest that C. albicans stimulates an autocrine loop in macrophages involving
      cPLA2alpha, cyclooxygenase 1-derived prostaglandins and increased cAMP that
      globally effects expression of genes involved in host defense and inflammation. 

PMID- 23950859
TI  - Low primary and secondary HIV drug-resistance after 12 months of antiretroviral
      therapy in human immune-deficiency virus type 1 (HIV-1)-infected individuals from
      Kigali, Rwanda.
AB  - Treatment outcomes of HIV patients receiving antiretroviral therapy (ART) in
      Rwanda are scarcely documented. HIV viral load (VL) and HIV drug-resistance
      (HIVDR) outcomes at month 12 were determined in a prospective cohort study of
      antiretroviral-naive HIV patients initiating first-line therapy in Kigali.
      Treatment response was monitored clinically and by regular CD4 counts and
      targeted HIV viral load (VL) to confirm drug failure. VL measurements and HIVDR
      genotyping were performed retrospectively on baseline and month 12 samples. One
      hundred and fifty-eight participants who completed their month 12 follow-up visit
      had VL data available at month 12. Most of them (88%) were virologically
      suppressed (VL<=1000 copies/mL) but 18 had virological failure (11%), which is in
      the range of WHO-suggested targets for HIVDR prevention. If only CD4 criteria had
      been used to classify treatment response, 26% of the participants would have been
      misclassified as treatment failure. Pre-therapy HIVDR was documented in 4 of 109
      participants (3.6%) with an HIVDR genotyping results at baseline. Eight of 12
      participants (66.7%) with virological failure and HIVDR genotyping results at
      month 12 were found to harbor mutation(s), mostly NNRTI resistance mutations,
      whereas 4 patients had no HIVDR mutations. Almost half (44%) of the participants
      initiated ART at CD4 count <=200 cell/ul and severe CD4 depletion at baseline
      (<50 cells/ul) was associated with virological treatment failure (p = 0.008).
      Although the findings may not be generalizable to all HIV patients in Rwanda, our
      data suggest that first-line ART regimen changes are currently not warranted.
      However, the accumulation of acquired HIVDR mutations in some participants
      underscores the need to reinforce HIVDR prevention strategies, such as increasing
      the availability and appropriate use of VL testing to monitor ART response,
      ensuring high quality adherence counseling, and promoting earlier identification
      of HIV patients and enrollment into HIV care and treatment programs.

PMID- 23950860
TI  - Stochastic responses may allow genetically diverse cell populations to optimize
      performance with simpler signaling networks.
AB  - Two theories have emerged for the role that stochasticity plays in biological
      responses: first, that it degrades biological responses, so the performance of
      biological signaling machinery could be improved by increasing molecular copy
      numbers of key proteins; second, that it enhances biological performance, by
      enabling diversification of population-level responses. Using T cell biology as
      an example, we demonstrate that these roles for stochastic responses are not
      sufficient to understand experimental observations of stochastic response in
      complex biological systems that utilize environmental and genetic diversity to
      make cooperative responses. We propose a new role for stochastic responses in
      biology: they enable populations to make complex responses with simpler
      biochemical signaling machinery than would be required in the absence of
      stochasticity. Thus, the evolution of stochastic responses may be linked to the
      evolvability of different signaling machineries.

PMID- 23950861
TI  - Non-smoking male adolescents' reactions to cigarette warnings.
AB  - BACKGROUND: The U.S. Food and Drug Administration (FDA) is working to introduce
      new graphic warning labels for cigarette packages, the first change in cigarette
      warnings in more than 25 years. We sought to examine whether warnings discouraged
      participants from wanting to smoke and altered perceived likelihood of harms
      among adolescent males and whether these warning effects varied by age. METHODS:
      A national sample of 386 non-smoking American males ages 11-17 participated in an
      online experiment during fall 2010. We randomly assigned participants to view
      warnings using a 2 * 2 between-subjects design. The warnings described a harm of
      smoking (addiction or lung cancer) using text only or text plus an image used on
      European cigarette package warnings. Analyses tested whether age moderated the
      warnings' impact on risk perceptions and smoking motivations. RESULTS: The
      warnings discouraged most adolescents from wanting to smoke, but lung cancer
      warnings discouraged them more than addiction warnings did (60% vs. 34% were
      "very much" discouraged, p<.001). Including an image had no effect on
      discouragement. The warnings affected several beliefs about the harms from
      smoking, and age moderated these effects. Adolescents said addiction was easier
      to imagine and more likely to happen to them than lung cancer. They also believed
      that their true likelihood of experiencing any harm was lower than what an expert
      would say. CONCLUSIONS: Our findings suggest that warnings focusing on lung
      cancer, rather than addiction, are more likely to discourage wanting to smoke
      among adolescent males and enhance their ability to imagine the harmful
      consequences of smoking. Including images on warnings had little effect on non
      smoking male adolescents' discouragement or beliefs, though additional research
      on the effects of pictorial warnings for this at-risk population is needed as the
      FDA moves forward with developing new graphic labels.

PMID- 23950862
TI  - Identification of novel gene targets and functions of p21-activated kinase 1
      during DNA damage by gene expression profiling.
AB  - P21-activated kinase 1 (PAK1), a serine/threonine protein kinase, modulates many
      cellular processes by phosphorylating its downstream substrates. In addition to
      its role in the cytoplasm, PAK1 also affects gene transcription due to its
      nuclear localization and association with chromatin. It is now recognized that
      PAK1 kinase activity and its nuclear translocation are rapidly stimulated by
      ionizing radiation (IR), and that PAK1 activation is a component of the DNA
      damage response. Owing to the role of PAK1 in the cell survival, its association
      with the chromatin, and now, stimulation by ionizing radiation, we hypothesize
      that PAK1 may be contributing to modulation of genes with roles in cellular
      processes that might be important in the DNA damage response. The purpose of this
      study was to identify new PAK1 targets in response to ionizing radiation with
      putative role in the DNA damage response. We examined the effect of IR on the
      gene expression patterns in the murine embryonic fibroblasts with or without Pak1
      using microarray technology. Differentially expressed transcripts were identified
      using Gene Spring GX 10.0.2. Pathway, network, functional analyses and gene
      family classification were carried out using Kyoto Encyclopedia of Genes and
      Genomes (KEGG), Ingenuity Pathway, Gene Ontology and PANTHER respectively.
      Selective targets of PAK1 were validated by RT-qPCR. For the first time, we
      provide a genome-wide analysis of PAK1 and identify its targets with potential
      roles in the DNA damage response. Gene Ontology analysis identified genes in the
      IR-stimulated cells that were involved in cell cycle arrest and cell death.
      Pathway analysis revealed p53 pathway being most influenced by IR responsive,
      PAK1 targets. Gene family of transcription factors was over represented and gene
      networks involved in DNA replication, repair and cellular signaling were
      identified. In brief, this study identifies novel PAK1 dependent IR responsive
      genes which reveal new aspects of PAK1 biology. 

PMID- 23950863
TI  - Knockdown a water channel protein, aquaporin-4, induced glioblastoma cell
      apoptosis.
AB  - Glioblastomas are the most aggressive forms of primary brain tumors due to their
      tendency to invade surrounding healthy brain tissues, rendering them largely
      incurable. The water channel protein, Aquaporin-4 (AQP4) is a key molecule for
      maintaining water and ion homeostasis in the central nervous system and has
      recently been reported with cell survival except for its well-known function in
      brain edema. An increased AQP4 expression has been demonstrated in glioblastoma
      multiforme (GBM), suggesting it is also involved in malignant brain tumors. In
      this study, we show that siRNA-mediated down regulation of AQP4 induced
      glioblastoma cell apoptosis in vitro and in vivo. We further show that several
      apoptotic key proteins, Cytochrome C, Bcl-2 and Bad are involved in AQP4
      signaling pathways. Our results indicate that AQP4 may serve as an anti-apoptosis
      target for therapy of glioblastoma. 

PMID- 23950864
TI  - Microarray-based identification of differentially expressed genes in
      intracellular Brucella abortus within RAW264.7 cells.
AB  - Brucella spp. is a species of facultative intracellular Gram-negative bacteria
      that induces abortion and causes sterility in domesticated mammals and chronic
      undulant fever in humans. Important determinants of Brucella's virulence and
      potential for chronic infection include the ability to circumvent the host cell's
      internal surveillance system and the capability to proliferate within dedicated
      and non-dedicated phagocytes. Hence, identifying genes necessary for
      intracellular survival may hold the key to understanding Brucella infection. In
      the present study, microarray analysis reveals that 7.82% (244/3334) of all
      Brucella abortus genes were up-regulated and 5.4% (180/3334) were down-regulated
      in RAW264.7 cells, compared to free-living cells in TSB. qRT-PCR verification
      further confirmed a >5-fold up-regulation for fourteen genes. Functional analysis
      classified araC, ddp, and eryD as to partake in information storage and
      processing, alp, flgF and virB9 to be involved in cellular processes, hpcd and
      aldh to play a role in metabolism, mfs and nikC to be involved in both cellular
      processes and metabolism, and four hypothetical genes (bruAb1_1814, bruAb1_0475,
      bruAb1_1926, and bruAb1_0292) had unknown functions. Furthermore, we constructed
      a B. abortus 2308 mutant Deltaddp where the ddp gene is deleted in order to
      evaluate the role of ddp in intracellular survival. Infection assay indicated
      significantly higher adherence and invasion abilities of the Deltaddp mutant,
      however it does not survive well in RAW264.7 cells. Brucella may survive in
      hostile intracellular environment by modulating gene expression. 

PMID- 23950865
TI  - Cystatin SN upregulation in patients with seasonal allergic rhinitis.
AB  - Seasonal allergic rhinitis (SAR) to the Japanese cedar, Cryptomeria japonica (JC)
      pollen is an IgE-mediated type I allergy affecting nasal mucosa. However, the
      molecular events underlying its development remain unclear. We sought to identify
      SAR-associated altered gene expression in nasal epithelial cells during natural
      exposure to JC pollen. We recruited study participants in 2009 and 2010 and
      collected nasal epithelial cells between February and April, which is the period
      of natural pollen dispersion. Fifteen patients with SAR-JC and 13 control
      subjects were enrolled in 2009, and 17 SAR-JC patients, 13 sensitized
      asymptomatic subjects (Sensitized), and 15 control subjects were enrolled in
      2010. Total RNA was extracted from nasal epithelial cells and 8 SAR-JC patients
      and 6 control subjects in 2009 were subjected to microarray analysis with the
      Illumina HumanRef-8 Expression BeadChip platform. Allergen-stimulated histamine
      release was examined in the peripheral blood basophils isolated from patients
      with SAR. We identified 32 genes with significantly altered expression during
      allergen exposure. One of these, CST1 encodes the cysteine protease inhibitor,
      cystatin SN. CST1 expression in nasal epithelial cells was significantly
      upregulated in both the 2009 and 2010 SAR-JC groups compared with the control
      groups. Immunohistochemical staining confirmed the increased expression of CST1
      in the nasal epithelial cells of SAR patients. Addition of exogenous CST1 to
      basophils inhibited JC allergen-stimulated histamine release in vitro. We propose
      that CST1 may contribute to inactivation of protease allergens and help re
      establish homeostasis of the nasal membranes. 

PMID- 23950866
TI  - Annexin A2 promotes the migration and invasion of human hepatocellular carcinoma
      cells in vitro by regulating the shedding of CD147-harboring microvesicles from
      tumor cells.
AB  - It has been reported that Annexin A2 (ANXA2) is up-regulated in hepatocellular
      carcinoma (HCC), but the roles of ANXA2 in the migration and invasion of HCC
      cells have not been determined. In this study, we found that ANXA2-specific siRNA
      (si-ANXA2) significantly inhibited the migration and invasion of HCC cells co
      cultured with fibroblasts in vitro. In addition, the production of MMP-2 by
      fibroblasts cultured in supernatant collected from si-ANXA2-transfected HCC cells
      was notably down-regulated. ANXA2 was also found to be co-localized and co
      immunoprecipitated with CD147. Further investigation revealed that the expression
      of ANXA2 in HCC cells affected the shedding of CD147-harboring membrane
      microvesicles, acting as a vehicle for CD147 in tumor-stromal interactions and
      thereby regulating the production of MMP-2 by fibroblasts. Together, these
      results suggest that ANXA2 enhances the migration and invasion potential of HCC
      cells in vitro by regulating the trafficking of CD147-harboring membrane
      microvesicles. 

PMID- 23950867
TI  - Genetic basis for spontaneous hybrid genome doubling during allopolyploid
      speciation of common wheat shown by natural variation analyses of the paternal
      species.
AB  - The complex process of allopolyploid speciation includes various mechanisms
      ranging from species crosses and hybrid genome doubling to genome alterations and
      the establishment of new allopolyploids as persisting natural entities.
      Currently, little is known about the genetic mechanisms that underlie hybrid
      genome doubling, despite the fact that natural allopolyploid formation is highly
      dependent on this phenomenon. We examined the genetic basis for the spontaneous
      genome doubling of triploid F1 hybrids between the direct ancestors of
      allohexaploid common wheat (Triticum aestivum L., AABBDD genome), namely
      Triticumturgidum L. (AABB genome) and Aegilopstauschii Coss. (DD genome). An Ae.
      tauschii intraspecific lineage that is closely related to the D genome of common
      wheat was identified by population-based analysis. Two representative accessions,
      one that produces a high-genome-doubling-frequency hybrid when crossed with a T.
      turgidum cultivar and the other that produces a low-genome-doubling-frequency
      hybrid with the same cultivar, were chosen from that lineage for further
      analyses. A series of investigations including fertility analysis,
      immunostaining, and quantitative trait locus (QTL) analysis showed that (1)
      production of functional unreduced gametes through nonreductional meiosis is an
      early step key to successful hybrid genome doubling, (2) first division
      restitution is one of the cytological mechanisms that cause meiotic nonreduction
      during the production of functional male unreduced gametes, and (3) six QTLs in
      the Ae. tauschii genome, most of which likely regulate nonreductional meiosis and
      its subsequent gamete production processes, are involved in hybrid genome
      doubling. Interlineage comparisons of Ae. tauschii's ability to cause hybrid
      genome doubling suggested an evolutionary model for the natural variation pattern
      of the trait in which non-deleterious mutations in six QTLs may have important
      roles. The findings of this study demonstrated that the genetic mechanisms for
      hybrid genome doubling could be studied based on the intrinsic natural variation
      that exists in the parental species. 

PMID- 23950868
TI  - Multi-criteria decision analysis tools for prioritising emerging or re-emerging
      infectious diseases associated with climate change in Canada.
AB  - Global climate change is known to result in the emergence or re-emergence of some
      infectious diseases. Reliable methods to identify the infectious diseases of
      humans and animals and that are most likely to be influenced by climate are
      therefore required. Since different priorities will affect the decision to
      address a particular pathogen threat, decision makers need a standardised method
      of prioritisation. Ranking methods and Multi-Criteria Decision approaches provide
      such a standardised method and were employed here to design two different
      pathogen prioritisation tools. The opinion of 64 experts was elicited to assess
      the importance of 40 criteria that could be used to prioritise emerging
      infectious diseases of humans and animals in Canada. A weight was calculated for
      each criterion according to the expert opinion. Attributes were defined for each
      criterion as a transparent and repeatable method of measurement. Two different
      Multi-Criteria Decision Analysis tools were tested, both of which used an
      additive aggregation approach. These were an Excel spreadsheet tool and a tool
      developed in software 'M-MACBETH'. The tools were trialed on nine 'test'
      pathogens. Two different methods of criteria weighting were compared, one using
      fixed weighting values, the other using probability distributions to account for
      uncertainty and variation in expert opinion. The ranking of the nine pathogens
      varied according to the weighting method that was used. In both tools, using both
      weighting methods, the diseases that tended to rank the highest were West Nile
      virus, Giardiasis and Chagas, while Coccidioidomycosis tended to rank the lowest.
      Both tools are a simple and user friendly approach to prioritising pathogens
      according to climate change by including explicit scoring of 40 criteria and
      incorporating weighting methods based on expert opinion. They provide a dynamic
      interactive method that can help to identify pathogens for which a full risk
      assessment should be pursued. 

PMID- 23950869
TI  - No serological evidence of influenza A H1N1pdm09 virus infection as a
      contributing factor in childhood narcolepsy after Pandemrix vaccination campaign
      in Finland.
AB  - BACKGROUND: Narcolepsy cataplexy syndrome, characterised by excessive daytime
      sleepiness and cataplexy, is strongly associated with a genetic marker, human
      leukocyte antigen (HLA) DQB1*06:02. A sudden increase in the incidence of
      childhood narcolepsy was observed after vaccination with AS03-adjuvanted
      Pandemrix influenza vaccine in Finland at the beginning of 2010. Here, we
      analysed whether the coinciding influenza A H1N1pdm pandemic contributed,
      together with the Pandemrix vaccination, to the increased incidence of childhood
      narcolepsy in 2010. The analysis was based on the presence or absence of antibody
      response against non-structural protein 1 (NS1) from H1N1pdm09 virus, which was
      not a component of Pandemrix vaccine. METHODS: Non-structural (NS) 1 proteins
      from recombinant influenza A/Udorn/72 (H3N2) and influenza A/Finland/554/09
      (H1N1pdm09) viruses were purified and used in Western blot analysis to determine
      specific antibody responses in human sera. The sera were obtained from 45
      patients who fell ill with narcolepsy after vaccination with AS03-adjuvanted
      Pandemrix at the end of 2009, and from controls. FINDINGS: Based on quantitative
      Western blot analysis, only two of the 45 (4.4%) Pandemrix-vaccinated narcoleptic
      patients showed specific antibody response against the NS1 protein from the
      H1N1pdm09 virus, indicating past infection with the H1N1pdm09 virus. Instead,
      paired serum samples from patients, who suffered from a laboratory confirmed
      H1N1pdm09 infection, showed high levels or diagnostic rises (96%) in H1N1pdm
      virus NS1-specific antibodies and very high cross-reactivity to H3N2 subtype
      influenza A virus NS1 protein. CONCLUSION: Based on our findings, it is unlikely
      that H1N1pdm09 virus infection contributed to a sudden increase in the incidence
      of childhood narcolepsy observed in Finland in 2010 after AS03-adjuvanted
      Pandemrix vaccination.

PMID- 23950871
TI  - A cohort study of the impact of tooth loss and periodontal disease on respiratory
      events among COPD subjects: modulatory role of systemic biomarkers of
      inflammation.
AB  - BACKGROUND: In COPD patients, fatal and non-fatal respiratory-related events are
      influenced by age, severity of respiratory disease, and comorbidities.
      OBJECTIVES: Analyze the effects of edentulism, periodontal disease and systemic
      biomarkers of inflammation on the occurrence of serious fatal and non-fatal
      respiratory-related events among subjects with COPD. METHODS: Cases were
      identified from Dental Atherosclerosis Risk in Communities study. Edentulism was
      defined as study participants without any natural teeth or implants. Participants
      with one or more natural teeth (comprising 11,378 subjects) were studied as
      dentate subjects. Periodontal disease status among dentate individuals was
      determined using the consensus definitions published by the joint Center for
      Disease Control/American Association of Periodontology working group). Adjusted
      Hazard Models are developed to evaluate the relationship between
      edentulism/periodontal disease and COPD Related Events. Models were then
      stratified by GOLD Stage I, II and III/IV. Serum biomarkers were also evaluated
      to explore the effect of systemic inflammation. RESULTS: A statistically
      significant association was found between oral health status and COPD-related
      events, even adjusting for conditions such as hypertension, smoking and diabetes.
      Edentulous individuals who had been diagnosed with COPD had a higher incidence
      and were at greater risk of having a COPD related event (hospitalization and
      death) than individuals who had teeth and whose mouths had healthy periodontal
      status. However, being edentulous did not convey excess risk for COPD-related
      events for those study participants who were classified as GOLD III/IV at
      baseline. Finally, we showed that individuals who had levels of serum IL-6 in the
      highest two quartiles were at even higher risk for COPD-related events.
      CONCLUSIONS: These findings suggest that the risk for COPD-related events after
      adjusting for potential confounders may be attributable to both edentulism and
      elevated serum IL-6 levels.

PMID- 23950870
TI  - Discovery and validation of DNA hypomethylation biomarkers for liver cancer using
      HRM-specific probes.
AB  - Poor prognosis of hepatocellular carcinoma (HCC) associated with late diagnosis
      necessitates the development of early diagnostic biomarkers. We have previously
      delineated the landscape of DNA methylation in HCC patients unraveling the
      importance of promoter hypomethylation in activation of cancer- and metastasis
      driving genes. The purpose of the present study was to test the feasibility that
      genes that are hypomethylated in HCC could serve as candidate diagnostic markers.
      We use high resolution melting analysis (HRM) as a simple translatable PCR-based
      method to define methylation states in clinical samples. We tested seven regions
      selected from the shortlist of genes hypomethylated in HCC and showed that HRM
      analysis of several of them distinguishes methylation states in liver cancer
      specimens from normal adjacent liver and chronic hepatitis in the Shanghai area.
      Such regions were identified within promoters of neuronal membrane glycoprotein
      M6-B (GPM6B) and melanoma antigen family A12 (MAGEA12) genes. Differences in HRM
      in the immunoglobulin superfamily Fc receptor (FCRL1) separated invasive tumors
      from less invasive HCC. The identified biomarkers differentiated HCC from chronic
      hepatitis in another set of samples from Dhaka. Although the main thrust in DNA
      methylation diagnostics in cancer is on hypermethylated genes, our study for the
      first time illustrates the potential use of hypomethylated genes as markers for
      solid tumors. After further validation in a larger cohort, the identified DNA
      hypomethylated regions can become important candidate biomarkers for liver cancer
      diagnosis and prognosis, especially in populations with high risk for HCC
      development. 

PMID- 23950872
TI  - Assessment of structural connectivity in the preterm brain at term equivalent age
      using diffusion MRI and T2 relaxometry: a network-based analysis.
AB  - Preterm birth is associated with a high prevalence of adverse neurodevelopmental
      outcome. Non-invasive techniques which can probe the neural correlates
      underpinning these deficits are required. This can be achieved by measuring the
      structural network of connections within the preterm infant's brain using
      diffusion MRI and tractography. We used diffusion MRI and T2 relaxometry to
      identify connections with altered white matter properties in preterm infants
      compared to term infants. Diffusion and T2 data were obtained from 9 term
      neonates and 18 preterm-born infants (born <32 weeks gestational age) at term
      equivalent age. Probabilistic tractography incorporating multiple fibre
      orientations was used in combination with the Johns Hopkins neonatal brain atlas
      to calculate the structural network of connections. Connections of altered
      diffusivity or T2, as well as their relationship with gestational age at birth
      and postmenstrual age at the time of MRI, were identified using the network based
      statistic framework. A total of 433 connections were assessed. FA was
      significantly reduced in 17, and T2 significantly increased in 18 connections in
      preterm infants, following correction for multiple comparisons. Cortical networks
      associated with affected connections mainly involved left frontal and temporal
      cortical areas: regions which are associated with working memory, verbal
      comprehension and higher cognitive function--deficits which are often observed
      later in children and adults born preterm. Gestational age at birth correlated
      with T2, but not diffusion in several connections. We found no association
      between diffusion or T2 and postmenstrual age at the time of MRI in preterm
      infants. This study demonstrates that alterations in the structural network of
      connections can be identified in preterm infants at term equivalent age, and that
      incorporation of non-diffusion measures such as T2 in the connectome framework
      provides complementary information for the assessment of brain development.

PMID- 23950873
TI  - Size-energy relationships in ecological communities.
AB  - Hypotheses that relate body size to energy use are of particular interest in
      community ecology and macroecology because of their potential to facilitate
      quantitative predictions about species interactions and to clarify complex
      ecological patterns. One prominent size-energy hypothesis, the energetic
      equivalence hypothesis, proposes that energy use from shared, limiting resources
      by populations or size classes of foragers will be independent of body size.
      Alternative hypotheses propose that energy use will increase with body size,
      decrease with body size, or peak at an intermediate body size. Despite extensive
      study, however, size-energy hypotheses remain controversial, due to a lack of
      directly-measured data on energy use, a tendency to confound distinct scaling
      relationships, and insufficient attention to the ecological contexts in which
      predicted relationships are likely to occur. Our goal, therefore, was to directly
      evaluate size-energy hypotheses while clarifying how results would differ with
      alternate methods and assumptions. We comprehensively tested size-energy
      hypotheses in a vertebrate frugivore guild in a tropical forest in Madagascar.
      Our test of size-energy hypotheses, which is the first to examine energy intake
      directly, was consistent with the energetic equivalence hypothesis. This finding
      corresponds with predictions of metabolic theory and models of energy
      distribution in ecological communities, which imply that body size does not
      confer an advantage in competition for energy among populations or size classes
      of foragers. This result was robust to different assumptions about energy
      regulation. Our results from direct energy measurement, however, contrasted with
      those obtained with conventional methods of indirect inference from size-density
      relationships, suggesting that size-density relationships do not provide an
      appropriate proxy for size-energy relationships as has commonly been assumed. Our
      research also provides insights into mechanisms underlying local size-energy
      relationships and has important implications for predicting species interactions
      and for understanding the structure and dynamics of ecological communities. 

PMID- 23950875
TI  - Discovery of a bovine enterovirus in alpaca.
AB  - A cytopathic virus was isolated using Madin-Darby bovine kidney (MDBK) cells from
      lung tissue of alpaca that died of a severe respiratory infection. To identify
      the virus, the infected cell culture supernatant was enriched for virus particles
      and a generic, PCR-based method was used to amplify potential viral sequences.
      Genomic sequence data of the alpaca isolate was obtained and compared with
      sequences of known viruses. The new alpaca virus sequence was most similar to
      recently designated Enterovirus species F, previously bovine enterovirus (BEVs),
      viruses that are globally prevalent in cattle, although they appear not to cause
      significant disease. Because bovine enteroviruses have not been previously
      reported in U.S. alpaca, we suspect that this type of infection is fairly rare,
      and in this case appeared not to spread beyond the original outbreak. The capsid
      sequence of the detected virus had greatest homology to Enterovirus F type 1
      (indicating that the virus should be considered a member of serotype 1), but the
      virus had greater homology in 2A protease sequence to type 3, suggesting that it
      may have been a recombinant. Identifying pathogens that infect a new host species
      for the first time can be challenging. As the disease in a new host species may
      be quite different from that in the original or natural host, the pathogen may
      not be suspected based on the clinical presentation, delaying diagnosis. Although
      this virus replicated in MDBK cells, existing standard culture and molecular
      methods could not identify it. In this case, a highly sensitive generic PCR-based
      pathogen-detection method was used to identify this pathogen. 

PMID- 23950874
TI  - CMV-independent lysis of glioblastoma by ex vivo expanded/activated Vdelta1+
      gammadelta T cells.
AB  - Vdelta2(neg) gammadelta T cells, of which Vdelta1+ gammadelta T cells are by far
      the largest subset, are important effectors against CMV infection. Malignant
      gliomas often contain CMV genetic material and proteins, and evidence exists that
      CMV infection may be associated with initiation and/or progression of
      glioblastoma multiforme (GBM). We sought to determine if Vdelta1+ gammadelta T
      cells were cytotoxic to GBM and the extent to which their cytotoxicity was CMV
      dependent. We examined the cytotoxic effect of ex vivo expanded/activated
      Vdelta1+ gammadelta T cells from healthy CMV seropositive and CMV seronegative
      donors on unmanipulated and CMV-infected established GBM cell lines and cell
      lines developed from short- term culture of primary tumors. Expanded/activated
      Vdelta1+ T cells killed CMV-negative U251, U87, and U373 GBM cell lines and two
      primary tumor explants regardless of the serologic status of the donor.
      Experimental CMV infection did not increase Vdelta1+ T cell--mediated
      cytotoxicity and in some cases the cell lines were more resistant to lysis when
      infected with CMV. Flow cytometry analysis of CMV-infected cell lines revealed
      down-regulation of the NKG2D ligands ULBP-2, and ULBP-3 as well as MICA/B in CMV
      infected cells. These studies show that ex vivo expanded/activated Vdelta1+
      gammadelta T cells readily recognize and kill established GBM cell lines and
      primary tumor-derived GBM cells regardless of whether CMV infection is present,
      however, CMV may enhance the resistance GBM cell lines to innate recognition
      possibly contributing to the poor immunogenicity of GBM.

PMID- 23950877
TI  - Categorizing ideas about trees: a tree of trees.
AB  - The aim of this study is to explore whether matrices and MP trees used to produce
      systematic categories of organisms could be useful to produce categories of ideas
      in history of science. We study the history of the use of trees in systematics to
      represent the diversity of life from 1766 to 1991. We apply to those ideas a
      method inspired from coding homologous parts of organisms. We discretize
      conceptual parts of ideas, writings and drawings about trees contained in 41 main
      writings; we detect shared parts among authors and code them into a 91-characters
      matrix and use a tree representation to show who shares what with whom. In other
      words, we propose a hierarchical representation of the shared ideas about trees
      among authors: this produces a "tree of trees." Then, we categorize schools of
      tree-representations. Classical schools like "cladists" and "pheneticists" are
      recovered but others are not: "gradists" are separated into two blocks, one of
      them being called here "grade theoreticians." We propose new interesting
      categories like the "buffonian school," the "metaphoricians," and those using
      "strictly genealogical classifications." We consider that networks are not useful
      to represent shared ideas at the present step of the study. A cladogram is made
      for showing who is sharing what with whom, but also heterobathmy and homoplasy of
      characters. The present cladogram is not modelling processes of transmission of
      ideas about trees, and here it is mostly used to test for proximity of ideas of
      the same age and for categorization. 

PMID- 23950876
TI  - Inhibition of both EGFR and IGF1R sensitized prostate cancer cells to radiation
      by synergistic suppression of DNA homologous recombination repair.
AB  - Reduced sensitivity of prostate cancer (PC) cells to radiation therapy poses a
      significant challenge in the clinic. Activation of epidermal growth factor
      receptor (EGFR), type 1 insulin-like growth factor receptor (IGF1R), and
      crosstalk between these two signaling pathways have been implicated in the
      development of radiation resistance in PC. This study assessed the effects of
      targeting both receptors on the regulation of radio-sensitivity in PC cells.
      Specific inhibitors of EGFR and IGF1R, Erlotinib and AG1024, as well as siRNA
      targeting EGFR and IGF1R, were used to radio-sensitize PC cells. Our results
      showed that co-inhibiting both receptors significantly dampened cellular growth
      and DNA damage repair, and increased radio-sensitivity in PC cells. These effects
      were carried out through synergistic inhibition of homologous recombination
      directed DNA repair (HRR), but not via inhibition of non-homologous end joining
      (NHEJ). Furthermore, the compromised HRR capacity was caused by reduced
      phosphorylation of insulin receptor substrate 1 (IRS1) and its subsequent
      interaction with Rad51. The synergistic effect of the EGFR and IGF1R inhibitors
      was also confirmed in nude mouse xenograft assay. This is the first study testing
      co-inhibiting EGFR and IGF1R signaling in the context of radio-sensitivity in PC
      and it may provide a promising adjuvant therapeutic approach to improve the
      outcome of PC patients to radiation treatment. 

PMID- 23950878
TI  - Lack of an association between CYP11B2 C-344T gene polymorphism and ischemic
      stroke: a meta-analysis of 7,710 subjects.
AB  - BACKGROUND: The association between aldosterone synthase (CYP11B2) C-344T gene
      polymorphism and ischemic stroke remains controversial and ambiguous. To better
      explain the association between CYP11B2 polymorphism and ischemic stroke risk, a
      meta-analysis was performed. METHODS: Based on comprehensive searches of Medline,
      Embase, Web of Science, CNKI and CBM databases, we identified and abstracted
      outcome data from all articles to evaluate the association between CYP11B2
      polymorphism and ischemic stroke. The pooled odds ratios (ORs) with 95%
      confidence intervals (CIs) were performed in all genetic models. Fixed or random
      effects model was separately used depending on the heterogeneity between studies.
      Publication bias was tested by Begg's funnel plot and Egger's regression test.
      RESULTS: A total of 12 studies including 3,620 ischemic stroke cases and 4,090
      controls were identified. There was no statistical evidence of association
      between CYP11B2 C-344T polymorphism and ischemic stroke in all genetic models
      (allelic model: OR = 1.19, 95% CI = 0.95-1.49; additive model: OR = 1.43, 95% CI
      = 0.91-2.27; dominant model: OR = 1.30, 95% CI = 0.89-1.89; and recessive model:
      OR = 1.24, 95% CI = 0.96-1.60). On subgroup analysis by ethnicity, similarly
      results were found in both Asians and non-Asians. For Asians, the combined ORs
      and 95% CIs were (allelic model: OR = 1.07, 95% CI = 0.87-1.32; additive model:
      OR = 1.15, 95% CI = 0.77-1.71; dominant model: OR = 1.13, 95% CI = 0.92-1.38; and
      recessive model: OR = 1.09, 95% CI = 0.84-1.40). For none-Asians, the combined
      ORs and 95% CIs were (allelic model: OR = 1.58, 95% CI = 0.90-2.76; additive
      model: OR = 2.37, 95% CI = 0.79-7.05; dominant model: OR = 1.79, 95% CI = 0.77
      4.19; and recessive model: OR = 1.80, 95% CI = 0.96-3.36). CONCLUSION: The
      present meta-analysis suggested that CYP11B2 C-344T polymorphism was unlikely
      contribute to ischemic stroke susceptibility.

PMID- 23950879
TI  - The contribution of emotional partners to sexual risk taking and violence among
      female sex workers in Mombasa, Kenya: a cohort study.
AB  - OBJECTIVES: To assess sexual risk-taking of female sex workers (FSWs) with
      emotional partners (boyfriends and husbands), compared to regular and casual
      clients. Experiences of violence and the degree of relationship control that FSWs
      have with emotional partners are also described. DESIGN: Cohort study with
      quarterly follow-up visit over 12-months. METHODS: Four hundred HIV-uninfected
      FSWs older than 16 years were recruited from their homes and guesthouses in
      Mombasa, Kenya. A structured questionnaire assessed participant characteristics
      and study outcomes at each visit, and women received risk-reduction counselling,
      male and female condoms, and HIV testing. RESULTS: Four or more unprotected sex
      acts in the past week were reported by 21.3% of women during sex with emotional
      partners, compared to 5.8% with regular and 4.8% with casual clients (P<0.001).
      Total number of unprotected sex acts per week was 5-6-fold higher with emotional
      partners (603 acts with 259 partners) than with regular or casual clients (125
      acts with 456, and 98 acts with 632 clients, respectively; P<0.001). Mostly,
      perceptions of "trust" underscored unprotected sex with emotional partners. Low
      control over these relationships, common to many women (36.9%), was linked with
      higher partner numbers, inconsistent condom use, and being physically forced to
      have sex by their emotional partners. Half experienced sexual or physical
      violence in the past year, similarly associated with partner numbers and
      inconsistent condom use. CONCLUSIONS: High-risk sexual behaviour, low control and
      frequent violence in relationships with emotional partners heighten FSWs'
      vulnerability and high HIV risk, requiring targeted interventions that also
      encompass emotional partners.

PMID- 23950880
TI  - Computational modeling reveals distinct effects of HIV and history of drug use on
      decision-making processes in women.
AB  - OBJECTIVE: Drug users and HIV-seropositive individuals often show deficits in
      decision-making; however the nature of these deficits is not well understood.
      Recent studies have employed computational modeling approaches to disentangle the
      psychological processes involved in decision-making. Although such approaches
      have been used successfully with a number of clinical groups including drug
      users, no study to date has used computational modeling to examine the effects of
      HIV on decision-making. In this study, we use this approach to investigate the
      effects of HIV and drug use on decision-making processes in women, who remain a
      relatively understudied population. METHOD: Fifty-seven women enrolled in the
      Women's Interagency HIV Study (WIHS) were classified into one of four groups
      based on their HIV status and history of crack cocaine and/or heroin drug use
      (DU): HIV+/DU+ (n = 14); HIV+/DU- (n = 17); HIV-/DU+ (n = 14); and HIV-/DU- (n =
      12). We measured decision-making with the Iowa Gambling Task (IGT) and examined
      behavioral performance and model parameters derived from the best-fitting
      computational model of the IGT. RESULTS: Although groups showed similar
      behavioral performance, HIV and DU exhibited differential relationship to model
      parameters. Specifically, DU was associated with compromised learning/memory and
      reduced loss aversion, whereas HIV was associated with reduced loss aversion, but
      was not related to other model parameters. CONCLUSIONS: Results reveal that HIV
      and DU have differential associations with distinct decision-making processes in
      women. This study contributes to a growing line of literature which shows that
      different psychological processes may underlie similar behavioral performance in
      various clinical groups and may be associated with distinct functional outcomes.

PMID- 23950881
TI  - Overexpression of the insulin receptor isoform A promotes endometrial carcinoma
      cell growth.
AB  - Epidemiological studies have demonstrated that type 2 diabetes mellitus (T2DM)
      and hyperinsulinemia are associated closely with endometrial carcinoma risk,
      although the molecular mechanism remains unclear. Insulin receptor isoformA
      expression is upregulated in many cancer cells and tissues, which suggests that
      IR-A-mediated signaling pathways may have important implications for cancer
      pathogenesis. We measured the expression of insulin receptor isoforms (IR-A and
      IR-B in the normal endometrium tissues, the endometrial carcinoma tissues and the
      endometrial carcinoma cell lines. We found that the total insulin receptor (IR)
      and IR-A expression mRNA levels and the ratio of IR-A to total IR in endometrial
      carcinoma specimens were significantly higher than them in control endometrial
      tissue specimens(P<0.05). Further analysis indicated that the tendency was more
      prominently in patients with T2DM. IR-A mRNA was differentially expressed in four
      endometrial carcinoma cell lines (Ishikawa, KLE, RL95-2 and HEC-1-A. RL95-2 cells
      have a low endogenous IR-A expression, and these were used to construct a stable
      cell line overexpressing IR-A. We found that IR-A overexpression significantly
      increased cell proliferation, the proportion of cells in S phase, activation of
      the Akt pathway and tumorigenicity of xenografts in nude mice. In contrast, there
      was no significant difference in the the percentage of apoptotic cells between
      cells overexpressing IR-A and control cells. Moreover, levels of phosphorylated
      ERK1/2 protein were significantly decreased in cells overexpressing IR-A relative
      to controls. These findings reveal the pivotal role of IR-A in endometrial cancer
      carcinogenesis, and suggest that the association of elevated IR-A levels with
      cell proliferation and tumorigenicity may be causally linked to its effect on the
      proportion of cells in S phase and the activation of the Akt pathway. 

PMID- 23950882
TI  - Socio-economic burden of influenza among children younger than 5 years in the
      outpatient setting in Suzhou, China.
AB  - BACKGROUND: The disease burden of children with laboratory-confirmed influenza in
      China has not been well described. The aim of this study was to understand the
      epidemiology and socio-economic burden of influenza in children younger than 5
      years in outpatient and emergency department settings. METHODS: A prospective
      study of laboratory-confirmed influenza among children presenting to the
      outpatient settings in Soochow University Affiliated Children's Hospital with
      symptoms of influenza-like illness (ILI) was performed from March 2011 to
      February 2012. Throat swabs were collected for detection of influenza virus by
      reverse transcription polymerase chain reaction assay. Data were collected using
      a researcher administered questionnaire, concerning demographics, clinical
      characteristics, direct and indirect costs, day care absence, parental work loss
      and similar respiratory illness development in the family. RESULTS: Among a total
      of 6,901 children who sought care at internal outpatient settings, 1,726 (25%)
      fulfilled the criteria of ILI and 1,537 were enrolled. Influenza was documented
      in 365 (24%) of enrolled 1,537 ILI cases. Among positive patients, 52 (14%) were
      type A and 313 (86%) were type B. About 52% of influenza outpatients had over-the
      counter medications before physician visit and 41% visited hospitals two or more
      times. Children who attended daycare missed an average of 1.9 days. For each
      child with influenza-confirmed disease, the parents missed a mean of 1.8 work
      days. Similar respiratory symptoms were reported in 43% of family contacts of
      influenza positive children after onset of the child's illness. The mean direct
      and indirect costs per episode of influenza were $123.4 for outpatient clinics
      and $134.6 for emergency departments, and $125.9 for influenza A and $127.5 for
      influenza B. CONCLUSIONS: Influenza is a common cause of influenza-like illness
      among children and has substantial socio-economic impact on children and their
      families regarding healthcare seeking and day care/work absence. The direct and
      indirect costs of childhood influenza impose a heavy financial burden on
      families. Prevention measures such as influenza vaccine could reduce the
      occurrence of influenza in children and the economic burden on families.

PMID- 23950883
TI  - Identification and characterization of three novel lipases belonging to families
      II and V from Anaerovibrio lipolyticus 5ST.
AB  - Following the isolation, cultivation and characterization of the rumen bacterium
      Anaerovibrio lipolyticus in the 1960s, it has been recognized as one of the major
      species involved in lipid hydrolysis in ruminant animals. However, there has been
      limited characterization of the lipases from the bacterium, despite the
      importance of understanding lipolysis and its impact on subsequent
      biohydrogenation of polyunsaturated fatty acids by rumen microbes. This study
      describes the draft genome of Anaerovibrio lipolytica 5ST, and the
      characterization of three lipolytic genes and their translated protein. The
      uncompleted draft genome was 2.83 Mbp and comprised of 2,673 coding sequences
      with a G+C content of 43.3%. Three putative lipase genes, alipA, alipB and alipC,
      encoding 492-, 438- and 248- amino acid peptides respectively, were identified
      using RAST. Phylogenetic analysis indicated that alipA and alipB clustered with
      the GDSL/SGNH family II, and alipC clustered with lipolytic enzymes from family
      V. Subsequent expression and purification of the enzymes showed that they were
      thermally unstable and had higher activities at neutral to alkaline pH. Substrate
      specificity assays indicated that the enzymes had higher hydrolytic activity
      against caprylate (C8), laurate (C12) and myristate (C14). 

PMID- 23950884
TI  - A possible explanation for the variable frequencies of cancer stem cells in
      tumors.
AB  - A controversy surrounds the frequency of cancer stem cells (CSCs) in solid
      tumors. Initial studies indicated that these cells had a frequency ranging from
      0.0001 to 0.1% of the total cells. Recent studies have shown that this does not
      always seem to be the case. Some of these studies have indicated a frequency of
      [Formula: see text]. In this paper we propose a stochastic model that is able to
      capture this potential variability in the frequency of CSCs among the various
      type of tumors. Considerations regarding the heterogeneity of the tumor cells and
      its consequences are included. Possible effects on conventional treatments in
      clinical practice are also described. The model results suggest that traditional
      attempts to combat cancer cells with rapid cycling can be very stimulating for
      the cancer stem cell populations.

PMID- 23950885
TI  - Intermittent explosive disorder amongst women in conflict affected Timor-Leste:
      associations with human rights trauma, ongoing violence, poverty, and injustice.
AB  - INTRODUCTION: Women in conflict-affected countries are at risk of mental
      disorders such as posttraumatic stress disorder and depression. No studies have
      investigated the association between experiences of abuse and injustice and
      explosive anger amongst women in these settings, and the impact of anger on
      women's health, family relationships and ability to participate in development.
      METHODS: A mixed methods study including an epidemiological survey (n = 1513,
      92.6% response) and qualitative interviews (n = 77) was conducted in Timor-Leste.
      The indices measured included Intermittent Explosive Disorder, posttraumatic
      stress disorder; severe distress; days out of role (the number of days that the
      person was unable to undertake normal activities); gender-specific trauma;
      conflict/violence; poverty; and preoccupations with injustice. RESULTS: Women
      with Intermittent Explosive Disorder (n = 184, 12.2%) were more disabled than
      those without the disorder (for >5 days out of role, 40.8% versus 31.5%, X(2) (2)
      = 12.93 p = 0.0016). Multivariable associations with Intermittent Explosive
      Disorder, controlling for the presence of PTSD, psychological distress and other
      predictors in the model, included the sense of being sick (OR 1.73; 95% CI 1.08
      2.77); victimization as a result of helping the resistance movement (OR 2.33, 95%
      CI 1.48-3.68); war-related trauma specific to being a woman (OR 1.95, 95%, CI
      1.09-3.50); ongoing family violence and community conflict (OR 1.88, 95% CI 1.27
      2.77); extreme poverty (OR 1.23, 95%, CI 1.08-1.39); and distressing
      preoccupations with injustice (relating to 2/3 historical periods, OR 2.10, 95%
      CI 1.35-3.28). In the qualitative study, women elaborated on the determinants of
      anger and its impact on their health, family and community functioning, child
      rearing, and capacity to engage in development. Women reflected on the strategies
      that might help them overcome their anger. CONCLUSIONS: Intermittent Explosive
      Disorder is prevalent and disabling amongst women in conflict-affected Timor
      Leste, impacting on their health, child-rearing and ability to participate fully
      in socio-economic development.

PMID- 23950886
TI  - Prostate gland lengths and iceball dimensions predict micturition functional
      outcome following salvage prostate cryotherapy in men with radiation recurrent
      prostate cancer.
AB  - INTRODUCTION: Tissue cryoablation is a potential curative option for solid
      malignancies, including radiation recurrent prostate cancer (RRPC). Case series
      of salvage cryotherapy (SCT) in RRPC have reported promising disease free
      survival (DFS) outcomes and acceptable toxicity profile. While many men receive
      SCT, no predictive factors for treatment induced side effects are known. The aim
      of this study is to validate the oncologic outcome of SCT in a large multi-centre
      patient cohort and to identify potential parameters associated with an increased
      risk of micturition symptoms. PATIENTS AND METHODS: In this retrospective
      analysis, we studied 283 consecutive patients with RRPC treated by SCT in three
      independent U.K. centres (between 2001 and 2011). Two freeze-thaw cycles of
      transperineal cryotherapy were performed under transrectal ultrasound guidance by
      a single surgeon in each of the 3 sites. We analysed clinico-pathological factors
      against tumour response. Functional outcomes were assessed by continence status
      and IPSS questionnaire. Predictive factors for SCT-induced micturition symptoms
      were analysed in a sub-group (n=42) of consecutive cases. RESULTS: We found that
      nadir post-SCT PSA levels strongly associated with DFS. The DFS rates at 12- and
      36-month were 84% and 67% for the <= 1 ng/ml group and 56% and 14% for the >1
      ng/ml group, respectively (p<0.001). Correlative analysis revealed highly
      significant association between patients' post-SCT micturition status with
      prostate gland and iceball lengths following SCT. Finally, in a reduction model,
      both gland length and maximal length of iceball were highly associated with
      patients' IPSS outcome (p<0.001). CONCLUSION: We report the largest European
      patient cohort treated with SCT for RRPC. Oncologic outcome guided by nadir PSA
      of <1 ng/ml is consistent with earlier single-centre series. For the first time,
      we identified physical parameters to predict micturition symptoms following SCT.
      Our data will directly assist on-going and future trial design in cryotherapy in
      prostate cancer.

PMID- 23950887
TI  - Lujiatun Psittacosaurids: understanding individual and taphonomic variation using
      3D geometric morphometrics.
AB  - Psittacosaurus is one of the most abundant and speciose genera in the Dinosauria,
      with fifteen named species. The genus is geographically and temporally widespread
      with large sample sizes of several of the nominal species allowing detailed
      analysis of intra- and interspecific variation. We present a reanalysis of three
      separate, coeval species within the Psittacosauridae; P. lujiatunensis, P. major,
      and Hongshanosaurus houi from the Lujiatun beds of the Yixian Formation,
      northeastern China, using three-dimensional geometric morphometrics on a sample
      set of thirty skulls in combination with a reevaluation of the proposed character
      states for each species. Using these complementary methods, we show that
      individual and taphonomic variation are the joint causes of a large range of
      variation among the skulls when they are plotted in a morphospace. Our results
      demonstrate that there is only one species of Psittacosaurus within the Lujiatun
      beds and that the three nominal species represent different taphomorphotypes of
      P. lujiatunensis. The wide range of geometric morphometric variation in a single
      species of Psittacosaurus implies that the range of variation found in other
      dinosaurian groups may also be related to taphonomic distortion rather than
      interspecific variation. As the morphospace is driven primarily by variation
      resulting from taphonomic distortion, this study demonstrates that the geometric
      morphometric approach can only be used with great caution to delineate
      interspecific variation in Psittacosaurus and likely other dinosaur groups
      without a complementary evaluation of character states. This study presents the
      first application of 3D geometric morphometrics to the dinosaurian morphospace
      and the first attempt to quantify taphonomic variation in dinosaur skulls. 

PMID- 23950888
TI  - MEK5/ERK5 signaling suppresses estrogen receptor expression and promotes hormone
      independent tumorigenesis.
AB  - Endocrine resistance and metastatic progression are primary causes of treatment
      failure in breast cancer. While mitogen activated protein kinases (MAPKs) are
      known to promote ligand-independent cell growth, the role of the MEK5-ERK5
      pathway in the progression of clinical breast carcinoma remains poorly
      understood. Here, we demonstrated increased ERK5 activation in 30 of 39 (76.9%)
      clinical tumor samples, as well as across breast cancer cell systems.
      Overexpression of MEK5 in MCF-7 cells promoted both hormone-dependent and hormone
      independent tumorigenesis in vitro and in vivo and conferred endocrine therapy
      resistance to previously sensitive breast cancer cells. Expression of MEK5
      suppressed estrogen receptor (ER)alpha, but not ER-beta protein levels, and
      abrogated downstream estrogen response element (ERE) transcriptional activity and
      ER-mediated gene transcription. Global gene expression changes associated with
      upregulation of MEK5 included increased activation of ER-alpha independent growth
      signaling pathways and promotion of epithelial-to-mesenchymal transition (EMT)
      markers. Taken together, our findings show that the MEK5-ERK5 pathway mediates
      progression to an ER(-), mesenchymal and endocrine therapy resistant phenotype.
      Given the need for new clinical therapeutic targets, our results demonstrate the
      therapeutic potential of targeting the MEK5-ERK5 pathway in breast cancer. 

PMID- 23950889
TI  - A whole-cell biosensor for the detection of gold.
AB  - Geochemical exploration for gold (Au) is becoming increasingly important to the
      mining industry. Current processes for Au analyses require sampling materials to
      be taken from often remote localities. Samples are then transported to a
      laboratory equipped with suitable analytical facilities, such as Inductively
      Coupled Plasma-Mass Spectrometry (ICP-MS) or Instrumental Neutron Activation
      Analysis (INAA). Determining the concentration of Au in samples may take several
      weeks, leading to long delays in exploration campaigns. Hence, a method for the
      on-site analysis of Au, such as a biosensor, will greatly benefit the exploration
      industry. The golTSB genes from Salmonella enterica serovar typhimurium are
      selectively induced by Au(I/III)-complexes. In the present study, the golTSB
      operon with a reporter gene, lacZ, was introduced into Escherichia coli. The
      induction of golTSB::lacZ with Au(I/III)-complexes was tested using a
      colorimetric beta-galactosidase and an electrochemical assay. Measurements of the
      beta-galactosidase activity for concentrations of both Au(I)- and Au(III)
      complexes ranging from 0.1 to 5 uM (equivalent to 20 to 1000 ng g(-1) or parts
      per-billion (ppb)) were accurately quantified. When testing the ability of the
      biosensor to detect Au(I/III)-complexes(aq) in the presence of other metal ions
      (Ag(I), Cu(II), Fe(III), Ni(II), Co(II), Zn, As(III), Pb(II), Sb(III) or
      Bi(III)), cross-reactivity was observed, i.e. the amount of Au measured was
      either under- or over-estimated. To assess if the biosensor would work with
      natural samples, soils with different physiochemical properties were spiked with
      Au-complexes. Subsequently, a selective extraction using 1 M thiosulfate was
      applied to extract the Au. The results showed that Au could be measured in these
      extracts with the same accuracy as ICP-MS (P<0.05). This demonstrates that by
      combining selective extraction with the biosensor system the concentration of Au
      can be accurately measured, down to a quantification limit of 20 ppb (0.1 uM) and
      a detection limit of 2 ppb (0.01 uM). 

PMID- 23950890
TI  - GPER mediates cardiotropic effects in spontaneously hypertensive rat hearts.
AB  - Estrogens promote beneficial effects in the cardiovascular system mainly through
      the estrogen receptor (ER)alpha and ERbeta, which act as ligand-gated
      transcription factors. Recently, the G protein-coupled estrogen receptor (GPER)
      has been implicated in the estrogenic signaling in diverse tissues, including the
      cardiovascular system. In this study, we demonstrate that left ventricles of male
      Spontaneously Hypertensive Rats (SHR) express higher levels of GPER compared to
      normotensive Wistar Kyoto (WKY) rats. In addition, we show that the selective
      GPER agonist G-1 induces negative inotropic and lusitropic effects to a higher
      extent in isolated and Langendorff perfused hearts of male SHR compared to WKY
      rats. These cardiotropic effects elicited by G-1 involved the GPER/eNOS
      transduction signaling, as determined by using the GPER antagonist G15 and the
      eNOS inhibitor L-NIO. Similarly, the G-1 induced activation of ERK1/2, AKT,
      GSK3beta, c-Jun and eNOS was abrogated by G15, while L-NIO prevented only the
      eNOS phosphorylation. In hypoxic Langendorff perfused WKY rat heart preparations,
      we also found an increased expression of GPER along with that of the hypoxic
      mediator HIF-1alpha and the fibrotic marker CTGF. Interestingly, G15 and L-NIO
      prevented the ability of G-1 to down-regulate the expression of both HIF-1alpha
      and CTGF, which were found expressed to a higher extent in SHR compared to WKY
      rat hearts. Collectively, the present study provides novel data into the
      potential role played by GPER in hypertensive disease on the basis of its
      involvement in myocardial inotropism and lusitropism as well as the expression of
      the apoptotic HIF-1alpha and fibrotic CTGF factors. Hence, GPER may be considered
      as a useful target in the treatment of some cardiac dysfunctions associated with
      stressful conditions like the essential hypertension. 

PMID- 23950891
TI  - Cerebral blood volume analysis in glioblastomas using dynamic susceptibility
      contrast-enhanced perfusion MRI: a comparison of manual and semiautomatic
      segmentation methods.
AB  - PURPOSE: To compare the reproducibilities of manual and semiautomatic
      segmentation method for the measurement of normalized cerebral blood volume
      (nCBV) using dynamic susceptibility contrast-enhanced (DSC) perfusion MR imaging
      in glioblastomas. MATERIALS AND METHODS: Twenty-two patients (11 male, 11 female;
      27 tumors) with histologically confirmed glioblastoma (WHO grade IV) were
      examined with conventional MR imaging and DSC imaging at 3T before surgery or
      biopsy. Then nCBV (means and standard deviations) in each mass was measured using
      two DSC MR perfusion analysis methods including manual and semiautomatic
      segmentation method, in which contrast-enhanced (CE)-T1WI and T2WI were used as
      structural imaging. Intraobserver and interobserver reproducibility were assessed
      according to each perfusion analysis method or each structural imaging.
      Interclass correlation coefficient (ICC), Bland-Altman plot, and coefficient of
      variation (CV) were used to evaluate reproducibility. RESULTS: Intraobserver
      reproducibilities on CE-T1WI and T2WI were ICC of 0.74-0.89 and CV of 20.39
      36.83% in manual segmentation method, and ICC of 0.95-0.99 and CV of 8.53-16.19%
      in semiautomatic segmentation method, repectively. Interobserver reproducibilites
      on CE-T1WI and T2WI were ICC of 0.86-0.94 and CV of 19.67-35.15% in manual
      segmentation method, and ICC of 0.74-1.0 and CV of 5.48-49.38% in semiautomatic
      segmentation method, respectively. Bland-Altman plots showed a good correlation
      with ICC or CV in each method. The semiautomatic segmentation method showed
      higher intraobserver and interobserver reproducibilities at CE-T1WI-based study
      than other methods. CONCLUSION: The best reproducibility was found using the
      semiautomatic segmentation method based on CE-T1WI for structural imaging in the
      measurement of the nCBV of glioblastomas.

PMID- 23950892
TI  - TNF stimulates nuclear export and secretion of IL-15 by acting on CRM1 and ARF6.
AB  - Interleukin (IL)-15 is a ubiquitously expressed cytokine that in the basal state
      is mainly localized intracellularly, including the nucleus. Unexpectedly, tumor
      necrosis factor-alpha (TNF) time-dependently induced nuclear export of IL
      15Ralpha and IL15. This process was inhibited by leptomycine B (LMB), a specific
      inhibitor of nuclear export receptor chromosomal region maintenance 1 (CRM1). In
      the presence of TNF, LMB co-treatment led to accumulation of both IL-15Ralpha and
      IL-15 in the nucleus of HeLa cells, suggesting that CRM1 facilitates nuclear
      export and that TNF enhances CRM1 activity. Once in the cytoplasm, IL-15 showed
      partial co-localization with late endosomes but very little with other organelles
      tested 4 h after TNF treatment. IL-15Ralpha showed co-localization with both
      early and late endosomes, and to a lesser extent with endoplasmic reticulum and
      Golgi. This indicates different kinetics and possibly different trafficking
      routes of IL-15 from its specific receptor. The TNF-induced secretion of IL-15
      was attenuated by pretreatment of cells by brefeldin A that inhibits ER-to-Golgi
      transport, or by use of domain negative ADP-ribosylation factor 6 (ARF6) that
      interferes with exocytotic sorting. We conclude that TNF abolishes nuclear
      localization of IL-15 and IL-15Ralpha by acting on CRM1, and it facilitates
      exocytosis of IL-15 with the involvement of ARF6. 

PMID- 23950895
TI  - Limited urban growth: London's street network dynamics since the 18th century.
AB  - We investigate the growth dynamics of Greater London defined by the
      administrative boundary of the Greater London Authority, based on the evolution
      of its street network during the last two centuries. This is done by employing a
      unique dataset, consisting of the planar graph representation of nine time slices
      of Greater London's road network spanning 224 years, from 1786 to 2010. Within
      this time-frame, we address the concept of the metropolitan area or city in
      physical terms, in that urban evolution reveals observable transitions in the
      distribution of relevant geometrical properties. Given that London has a hard
      boundary enforced by its long standing green belt, we show that its street
      network dynamics can be described as a fractal space-filling phenomena up to a
      capacitated limit, whence its growth can be predicted with a striking level of
      accuracy. This observation is confirmed by the analytical calculation of key
      topological properties of the planar graph, such as the topological growth of the
      network and its average connectivity. This study thus represents an example of a
      strong violation of Gibrat's law. In particular, we are able to show analytically
      how London evolves from a more loop-like structure, typical of planned cities,
      toward a more tree-like structure, typical of self-organized cities. These
      observations are relevant to the discourse on sustainable urban planning with
      respect to the control of urban sprawl in many large cities which have developed
      under the conditions of spatial constraints imposed by green belts and hard urban
      boundaries. 

PMID- 23950894
TI  - Stress-induced allodynia--evidence of increased pain sensitivity in healthy
      humans and patients with chronic pain after experimentally induced psychosocial
      stress.
AB  - BACKGROUND: Experimental stress has been shown to have analgesic as well as
      allodynic effect in animals. Despite the obvious negative influence of stress in
      clinical pain conditions, stress-induced alteration of pain sensitivity has not
      been tested in humans so far. Therefore, we tested changes of pain sensitivity
      using an experimental stressor in ten female healthy subjects and 13 female
      patients with fibromyalgia. METHODS: Multiple sensory aspects of pain were
      evaluated in all participants with the help of the quantitative sensory testing
      protocol before (60 min) and after (10 and 90 min) inducing psychological stress
      with a standardized psychosocial stress test ("Trier Social Stress Test").
      RESULTS: Both healthy subjects and patients with fibromyalgia showed stress
      induced enhancement of pain sensitivity in response to thermal stimuli. However,
      only patients showed increased sensitivity in response to pressure pain.
      CONCLUSIONS: Our results provide evidence for stress-induced
      allodynia/hyperalgesia in humans for the first time and suggest differential
      underlying mechanisms determining response to stressors in healthy subjects and
      patients suffering from chronic pain. Possible mechanisms of the interplay of
      stress and mediating factors (e.g. cytokines, cortisol) on pain sensitivity are
      mentioned. Future studies should help understand better how stress impacts on
      chronic pain conditions.

PMID- 23950896
TI  - Chemoprevention of skin cancer with 1,1-Bis (3'-indolyl)-1-(aromatic) methane
      analog through induction of the orphan nuclear receptor, NR4A2 (Nurr1).
AB  - BACKGROUND: The objective of this study was to demonstrate the anti-skin cancer
      and chemopreventive potential of 1,1-bis(3'-indolyl)-1-(p-chlorophenyl methane)
      (DIM-D) using an in vitro model. METHODS: In vitro cell cytotoxicity and
      viability assays were carried out in A431 human epidermoid carcinoma cell line
      and normal human epidermal keratinocytes (NHEK) respectively by crystal violet
      staining. Apoptosis induction in A431 cells (DIM-D treated) and NHEK cells
      pretreated with DIM-D (2 hr) prior to UVB irradiation, were assessed. The
      accumulation of reactive oxygen species (ROS) in DIM-D pretreated NHEK cells (2
      hr) prior to UVB exposure was also determined. Immunocytochemistry and western
      blot analysis was performed to determine cleaved caspase 3 and DNA damage markers
      in DIM-D treated A431 cells and in DIM-D pretreated NHEK cells prior to UVB
      irradiation. RESULTS: The IC50 values of DIM-D were 68.7 +/- 7.3, 48.3 +/- 10.1
      and 11.5 +/- 3.1 MUM whilst for Epigallocatechin gallate (EGCG) were 419.1 +/-
      8.3, 186.1 +/- 5.2 and 56.7 +/- 3.1 MUM for 24, 48 and 72 hr treatments
      respectively. DIM-D exhibited a significantly (p<0.05) greater induction of DNA
      fragmentation in A431 cells compared to EGCG with percent cell death of 38.9. In
      addition, DIM-D induced higher expression in A431 cells compared to EGCG of
      cleaved caspase 3 (3.0-fold vs. 2.4-fold changes), Nurr1 (2.7-fold vs. 1.7-fold
      changes) and NFkappaB (1.3-fold vs. 1.1-fold changes). DIM-D also exhibited
      chemopreventive activity in UVB-irradiated NHEK cells by significantly (p<0.05)
      reducing UVB-induced ROS formation and apoptosis compared to EGCG. Additionally,
      DIM-D induced expression of Nurr1 but reduced expression of 8-OHdG significantly
      in UVB-irradiated NHEK cells compared to EGCG and UV only. CONCLUSION: Our
      results suggest that DIM-D exhibits Nurr1-dependent transactivation in the
      induction of apoptosis in A431 cells and it protects NHEK cells against UVB
      induced ROS formation and DNA damage.

PMID- 23950893
TI  - PTPN22 association in systemic lupus erythematosus (SLE) with respect to
      individual ancestry and clinical sub-phenotypes.
AB  - Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative
      regulator of T-cell activation associated with several autoimmune diseases,
      including systemic lupus erythematosus (SLE). Missense rs2476601 is associated
      with SLE in individuals with European ancestry. Since the rs2476601 risk allele
      frequency differs dramatically across ethnicities, we assessed robustness of
      PTPN22 association with SLE and its clinical sub-phenotypes across four
      ethnically diverse populations. Ten SNPs were genotyped in 8220 SLE cases and
      7369 controls from in European-Americans (EA), African-Americans (AA), Asians
      (AS), and Hispanics (HS). We performed imputation-based association followed by
      conditional analysis to identify independent associations. Significantly
      associated SNPs were tested for association with SLE clinical sub-phenotypes,
      including autoantibody profiles. Multiple testing was accounted for by using
      false discovery rate. We successfully imputed and tested allelic association for
      107 SNPs within the PTPN22 region and detected evidence of ethnic-specific
      associations from EA and HS. In EA, the strongest association was at rs2476601 (P
      = 4.7 * 10(-9), OR = 1.40 (95% CI = 1.25-1.56)). Independent association with
      rs1217414 was also observed in EA, and both SNPs are correlated with increased
      European ancestry. For HS imputed intronic SNP, rs3765598, predicted to be a cis
      eQTL, was associated (P = 0.007, OR = 0.79 and 95% CI = 0.67-0.94). No
      significant associations were observed in AA or AS. Case-only analysis using
      lupus-related clinical criteria revealed differences between EA SLE patients
      positive for moderate to high titers of IgG anti-cardiolipin (aCL IgG >20) versus
      negative aCL IgG at rs2476601 (P = 0.012, OR = 1.65). Association was reinforced
      when these cases were compared to controls (P = 2.7 * 10(-5), OR = 2.11). Our
      results validate that rs2476601 is the most significantly associated SNP in
      individuals with European ancestry. Additionally, rs1217414 and rs3765598 may be
      associated with SLE. Further studies are required to confirm the involvement of
      rs2476601 with aCL IgG.

PMID- 23950897
TI  - Relationship between HIV stigma and self-isolation among people living with HIV
      in Tennessee.
AB  - INTRODUCTION: HIV stigma is a contributing factor to poor patient outcomes.
      Although HIV stigma has been documented, its impact on patient well-being in the
      southern US is not well understood. METHODS: Thirty-two adults participated in
      cognitive interviews after completing the Berger HIV or the Van Rie stigma scale.
      Participant responses were probed to ensure the scales accurately measured stigma
      and to assess the impact stigma had on behavior. RESULTS: Three main themes
      emerged regarding HIV stigma: (1) negative attitudes, fear of contagion, and
      misperceptions about transmission; (2) acts of discrimination by families,
      friends, health care providers, and within the workplace; and (3) participants'
      use of self-isolation as a coping mechanism. Overwhelming reluctance to disclose
      a person's HIV status made identifying enacted stigma with a quantitative scale
      difficult. DISCUSSION: Fear of discrimination resulted in participants isolating
      themselves from friends or experiences to avoid disclosure. Participant
      unwillingness to disclose their HIV status to friends and family could lead to an
      underestimation of enacted HIV stigma in quantitative scales.

PMID- 23950898
TI  - Exaggerated intergroup bias in economical decision making games: differential
      effects of primary and secondary psychopathic traits.
AB  - Psychopathic personality traits are linked with selfish and non-cooperative
      responses during economical decision making games. However, the possibility that
      these responses may vary when responding to members of the in-group and the out
      group has not yet been explored. We aimed to examine the effects of primary
      (selfish, uncaring) and secondary (impulsive, irresponsible) psychopathic
      personality traits on the responses of non-offending participants to the in-group
      and the out-group (defined in terms of affiliation to a UK University) across a
      series of economical decision making games. We asked a total of 60 participants
      to act as the proposer in both the dictator game and the ultimatum game. We found
      that across both tasks, those who scored highly for secondary psychopathic traits
      showed an elevated intergroup bias, making more generous offers toward members of
      the in-group relative to the out-group. An exaggerated intergroup bias may
      therefore represent a motivational factor for the antisocial behavior of those
      with elevated secondary psychopathic traits. 

PMID- 23950900
TI  - Revisiting the two-layer hypothesis: coexistence of alternative functional
      rooting strategies in savannas.
AB  - The two-layer hypothesis of tree-grass coexistence posits that trees and grasses
      differ in rooting depth, with grasses exploiting soil moisture in shallow layers
      while trees have exclusive access to deep water. The lack of clear differences in
      maximum rooting depth between these two functional groups, however, has caused
      this model to fall out of favor. The alternative model, the demographic
      bottleneck hypothesis, suggests that trees and grasses occupy overlapping rooting
      niches, and that stochastic events such as fires and droughts result in episodic
      tree mortality at various life stages, thus preventing trees from otherwise
      displacing grasses, at least in mesic savannas. Two potential problems with this
      view are: 1) we lack data on functional rooting profiles in trees and grasses,
      and these profiles are not necessarily reflected by differences in maximum or
      physical rooting depth, and 2) subtle, difficult-to-detect differences in rooting
      profiles between the two functional groups may be sufficient to result in
      coexistence in many situations. To tackle this question, I coupled a plant uptake
      model with a soil moisture dynamics model to explore the environmental conditions
      under which functional rooting profiles with equal rooting depth but different
      depth distributions (i.e., shapes) can coexist when competing for water. I show
      that, as long as rainfall inputs are stochastic, coexistence based on rooting
      differences is viable under a wide range of conditions, even when these
      differences are subtle. The results also indicate that coexistence mechanisms
      based on rooting niche differentiation are more viable under some climatic and
      edaphic conditions than others. This suggests that the two-layer model is both
      viable and stochastic in nature, and that a full understanding of tree-grass
      coexistence and dynamics may require incorporating fine-scale rooting differences
      between these functional groups and realistic stochastic climate drivers into
      future models. 

PMID- 23950899
TI  - Estimating kidney function in HIV-infected adults in Kenya: comparison to a
      direct measure of glomerular filtration rate by iohexol clearance.
AB  - BACKGROUND: More than two-thirds of the world's HIV-positive individuals live in
      sub-Saharan Africa, where genetic susceptibility to kidney disease is high and
      resources for kidney disease screening and antiretroviral therapy (ART) toxicity
      monitoring are limited. Equations to estimate glomerular filtration rate (GFR)
      from serum creatinine were derived in Western populations and may be less
      accurate in this population. METHODS: We compared results from published GFR
      estimating equations with a direct measure of GFR by iohexol clearance in 99 HIV
      infected, ART-naive Kenyan adults. Iohexol concentration was measured from dried
      blood spots on filter paper. The bias ratio (mean of the ratio of estimated to
      measured GFR) and accuracy (percentage of estimates within 30% of the measured
      GFR) were calculated. RESULTS: The median age was 35 years, and 60% were women.
      The majority had asymptomatic HIV, with median CD4+ cell count of 355
      cells/mm(3). Median measured GFR was 115 mL/min/1.73 m(2). Overall accuracy was
      highest for the Chronic Kidney Disease Epidemiology Consortium (CKD-EPI)
      equation. Consistent with a prior report, bias and accuracy were improved by
      eliminating the coefficient for black race (85% of estimates within 30% of
      measured GFR). Accuracy of all equations was poor in participants with GFR 60-90
      mL/min/1.73 m(2) (<65% of estimates within 30% of measured GFR), although this
      subgroup was too small to reach definitive conclusions. CONCLUSIONS: Overall
      accuracy was highest for the CKD-EPI equation. Eliminating the coefficient for
      race further improved performance. Future studies are needed to determine the
      most accurate GFR estimate for use in individuals with GFR <90 mL/min/1.73 m(2),
      in whom accurate estimation of kidney function is important to guide drug dosing.
      Direct measurement of GFR by iohexol clearance using a filter paper based assay
      is feasible for research purposes in resource-limited settings, and could be used
      to develop more accurate GFR estimates in African populations.

PMID- 23950901
TI  - The SULFs, extracellular sulfatases for heparan sulfate, promote the migration of
      corneal epithelial cells during wound repair.
AB  - Corneal epithelial wound repair involves the migration of epithelial cells to
      cover the defect followed by the proliferation of the cells to restore thickness.
      Heparan sulfate proteoglycans (HSPGs) are ubiquitous extracellular molecules that
      bind to a plethora of growth factors, cytokines, and morphogens and thereby
      regulate their signaling functions. Ligand binding by HS chains depends on the
      pattern of four sulfation modifications, one of which is 6-O-sulfation of
      glucosamine (6OS). SULF1 and SULF2 are highly homologous, extracellular
      endosulfatases, which post-synthetically edit the sulfation status of HS by
      removing 6OS from intact chains. The SULFs thereby modulate multiple signaling
      pathways including the augmentation of Wnt/beta-catenin signaling. We found that
      wounding of mouse corneal epithelium stimulated SULF1 expression in superficial
      epithelial cells proximal to the wound edge. Sulf1-/-, but not Sulf2-/-, mice,
      exhibited a marked delay in healing. Furthermore, corneal epithelial cells
      derived from Sulf1-/- mice exhibited a reduced rate of migration in repair of a
      scratched monolayer compared to wild-type cells. In contrast, human primary
      corneal epithelial cells expressed SULF2, as did a human corneal epithelial cell
      line (THCE). Knockdown of SULF2 in THCE cells also slowed migration, which was
      restored by overexpression of either mouse SULF2 or human SULF1. The
      interchangeability of the two SULFs establishes their capacity for functional
      redundancy. Knockdown of SULF2 decreased Wnt/beta-catenin signaling in THCE
      cells. Extracellular antagonists of Wnt signaling reduced migration of THCE
      cells. However in SULF2- knockdown cells, these antagonists exerted no further
      effects on migration, consistent with the SULF functioning as an upstream
      regulator of Wnt signaling. Further understanding of the mechanistic action of
      the SULFs in promoting corneal repair may lead to new therapeutic approaches for
      the treatment of corneal injuries.

PMID- 23950902
TI  - The interactions in the carboxyl terminus of human 4-hydroxyphenylpyruvate
      dioxygenase are critical to mediate the conformation of the final helix and the
      tail to shield the active site for catalysis.
AB  - 4-Hydroxylphenylpyruvate dioxygenase (4-HPPD) is an important enzyme for tyrosine
      catabolism, which catalyzes the conversion of 4-hydroxylphenylpyruvate (4-HPP) to
      homogentisate. In the present study, human 4-HPPD was cloned and expressed in E.
      coli. The kinetic parameters for 4-HPP conversion were: k cat=2.2 +/- 0.1 s(-1);
      and K m=0.08 +/- 0.02 mM. Sequence alignments show that human 4-HPPD possesses an
      extended C-terminus compared to other 4-HPPD enzymes. Successive truncation of
      the disordered tail which follows the final alpha-helix resulted in no changes in
      the K m value for 4-HPP substrate but the k cat values were significantly
      reduced. The results suggest that this disordered C-terminal tail plays an
      important role in catalysis. For inspection the effect of terminal truncation on
      protein structure, mutant models were built. These models suggest that the
      different conformation of E254, R378 and Q375 in the final helix might be the
      cause of the activity loss. In the structure E254 interacts with R378, the end
      residue in the final helix; mutation of either one of these residues causes a ca.
      95% reductions in k cat values. Q375 provides bifurcate interactions to fix the
      tail and the final helix in position. The model of the Q375N mutant shows that a
      solvent accessible channel opens to the putative substrate binding site,
      suggesting this is responsible for the complete loss of activity. These results
      highlight the critical role of Q375 in orientating the tail and ensuring the
      conformation of the terminal alpha-helix to maintain the integrity of the active
      site for catalysis.

PMID- 23950903
TI  - Age-related changes in expectation-based modulation of motion detectability.
AB  - Expecting motion in some particular direction biases sensitivity to that
      direction, which speeds detection of motion. However, the neural processes
      underlying this effect remain underexplored, especially in the context of normal
      aging. To address this, we examined younger and older adults' performance in a
      motion detection task. In separate conditions, the probability was either 50% or
      100% that a field of dots would move coherently in the direction a participant
      expected (either vertically or horizontally). Expectation and aging effects were
      assessed via response times (RT) to detect motion and electroencephalography
      (EEG). In both age groups, RTs were fastest when motion was similar to the
      expected direction of motion. RT tuning curves exhibited a characteristic U-shape
      such that detection time increased with an increasing deviation from the
      participant's expected direction. Strikingly, EEG results showed an analogous,
      hyperbolic curve for N1 amplitude, reflecting neural biasing. Though the form of
      behavioral and EEG curves did not vary with age, older adults displayed a clear
      decline in the speed of detection and a corresponding reduction in EEG N1
      amplitude when horizontal (but not vertical) motion was expected. Our results
      suggest that expectation-based detection ability varies with age and, for older
      adults, also with axis of motion. 

PMID- 23950904
TI  - Eyjafjallajokull and 9/11: the impact of large-scale disasters on worldwide
      mobility.
AB  - Large-scale disasters that interfere with globalized socio-technical
      infrastructure, such as mobility and transportation networks, trigger high socio
      economic costs. Although the origin of such events is often geographically
      confined, their impact reverberates through entire networks in ways that are
      poorly understood, difficult to assess, and even more difficult to predict. We
      investigate how the eruption of volcano Eyjafjallajokull, the September 11th
      terrorist attacks, and geographical disruptions in general interfere with
      worldwide mobility. To do this we track changes in effective distance in the
      worldwide air transportation network from the perspective of individual airports.
      We find that universal features exist across these events: airport
      susceptibilities to regional disruptions follow similar, strongly heterogeneous
      distributions that lack a scale. On the other hand, airports are more uniformly
      susceptible to attacks that target the most important hubs in the network,
      exhibiting a well-defined scale. The statistical behavior of susceptibility can
      be characterized by a single scaling exponent. Using scaling arguments that
      capture the interplay between individual airport characteristics and the
      structural properties of routes we can recover the exponent for all types of
      disruption. We find that the same mechanisms responsible for efficient passenger
      flow may also keep the system in a vulnerable state. Our approach can be applied
      to understand the impact of large, correlated disruptions in financial systems,
      ecosystems and other systems with a complex interaction structure between
      heterogeneous components. 

PMID- 23950905
TI  - Investigation into the value of trained glycaemia alert dogs to clients with type
      I diabetes.
AB  - Previous studies have suggested that some pet dogs respond to their owners'
      hypoglycaemic state. Here, we show that trained glycaemia alert dogs placed with
      clients living with diabetes afford significant improvements to owner well-being.
      We investigated whether trained dogs reliably respond to their owners'
      hypoglycaemic state, and whether owners experience facilitated tightened
      glycaemic control, and wider psychosocial benefits. Since obtaining their dog,
      all seventeen clients studied reported positive effects including reduced
      paramedic call outs, decreased unconscious episodes and improved independence.
      Owner-recorded data showed that dogs alerted their owners, with significant,
      though variable, accuracy at times of low and high blood sugar. Eight out of the
      ten dogs (for which owners provided adequate records) responded consistently more
      often when their owner's blood sugars were reported to be outside, than within,
      target range. Comparison of nine clients' routine records showed significant
      overall change after obtaining their dogs, with seven clients recording a
      significantly higher proportion of routine tests within target range after
      obtaining a dog. HbA1C showed a small, non significant reduction after dog
      allocation. Based on owner-reported data we have shown, for the first time, that
      trained detection dogs perform above chance level. This study points to the
      potential value of alert dogs, for increasing glycaemic control, client
      independence and consequent quality of life and even reducing the costs of long
      term health care. 

PMID- 23950906
TI  - Beyond reasonable doubt: evolution from DNA sequences.
AB  - We demonstrate quantitatively that, as predicted by evolutionary theory,
      sequences of homologous proteins from different species converge as we go further
      and further back in time. The converse, a non-evolutionary model can be expressed
      as probabilities, and the test works for chloroplast, nuclear and mitochondrial
      sequences, as well as for sequences that diverged at different time depths. Even
      on our conservative test, the probability that chance could produce the observed
      levels of ancestral convergence for just one of the eight datasets of 51 proteins
      is ~1*10-19 and combined over 8 datasets is ~1*10-132. By comparison, there are
      about 1080 protons in the universe, hence the probability that the sequences
      could have been produced by a process involving unrelated ancestral sequences is
      about 1050 lower than picking, among all protons, the same proton at random twice
      in a row. A non-evolutionary control model shows no convergence, and only a small
      number of parameters are required to account for the observations. It is time
      that that researchers insisted that doubters put up testable alternatives to
      evolution.

PMID- 23950907
TI  - Immunohistochemical, ultrastructural and functional analysis of axonal
      regeneration through peripheral nerve grafts containing Schwann cells expressing
      BDNF, CNTF or NT3.
AB  - We used morphological, immunohistochemical and functional assessments to
      determine the impact of genetically-modified peripheral nerve (PN) grafts on
      axonal regeneration after injury. Grafts were assembled from acellular nerve
      sheaths repopulated ex vivo with Schwann cells (SCs) modified to express brain
      derived neurotrophic factor (BDNF), a secretable form of ciliary neurotrophic
      factor (CNTF), or neurotrophin-3 (NT3). Grafts were used to repair unilateral 1
      cm defects in rat peroneal nerves and 10 weeks later outcomes were compared to
      normal nerves and various controls: autografts, acellular grafts and grafts with
      unmodified SCs. The number of regenerated betaIII-Tubulin positive axons was
      similar in all grafts with the exception of CNTF, which contained the fewest
      immunostained axons. There were significantly lower fiber counts in acellular,
      untransduced SC and NT3 groups using a PanNF antibody, suggesting a paucity of
      large caliber axons. In addition, NT3 grafts contained the greatest number of
      sensory fibres, identified with either IB4 or CGRP markers. Examination of semi-
      and ultra-thin sections revealed heterogeneous graft morphologies, particularly
      in BDNF and NT3 grafts in which the fascicular organization was pronounced.
      Unmyelinated axons were loosely organized in numerous Remak bundles in NT3
      grafts, while the BDNF graft group displayed the lowest ratio of umyelinated to
      myelinated axons. Gait analysis revealed that stance width was increased in rats
      with CNTF and NT3 grafts, and step length involving the injured left hindlimb was
      significantly greater in NT3 grafted rats, suggesting enhanced sensory
      sensitivity in these animals. In summary, the selective expression of BDNF, CNTF
      or NT3 by genetically modified SCs had differential effects on PN graft
      morphology, the number and type of regenerating axons, myelination, and locomotor
      function. 

PMID- 23950908
TI  - Is bone tissue really affected by swimming? A systematic review.
AB  - BACKGROUND: Swimming, a sport practiced in hypogravity, has sometimes been
      associated with decreased bone mass. AIM: This systematic review aims to
      summarize and update present knowledge about the effects of swimming on bone
      mass, structure and metabolism in order to ascertain the effects of this sport on
      bone tissue. METHODS: A literature search was conducted up to April 2013. A total
      of 64 studies focusing on swimmers bone mass, structure and metabolism met the
      inclusion criteria and were included in the review. RESULTS: It has been
      generally observed that swimmers present lower bone mineral density than athletes
      who practise high impact sports and similar values when compared to sedentary
      controls. However, swimmers have a higher bone turnover than controls resulting
      in a different structure which in turn results in higher resistance to fracture
      indexes. Nevertheless, swimming may become highly beneficial regarding bone mass
      in later stages of life. CONCLUSION: Swimming does not seem to negatively affect
      bone mass, although it may not be one of the best sports to be practised in order
      to increase this parameter, due to the hypogravity and lack of impact
      characteristic of this sport. Most of the studies included in this review showed
      similar bone mineral density values in swimmers and sedentary controls. However,
      swimmers present a higher bone turnover than sedentary controls that may result
      in a stronger structure and consequently in a stronger bone.

PMID- 23950910
TI  - Inter-individual and inter-strain variations in zebrafish locomotor ontogeny.
AB  - Zebrafish exhibit remarkable alterations in behaviour and morphology as they
      develop from early larval stages to mature adults. In this study we compare the
      locomotion parameters of six common zebrafish strains from two different
      laboratories to determine the stability and repeatability of these behaviours.
      Our results demonstrate large variability in locomotion and fast swim events
      between strains and between laboratories across time. These data highlight the
      necessity for careful, strain-specific controls when analysing locomotor
      phenotypes and open up the possibility of standardising the quantification of
      zebrafish behaviour at multiple life stages. 

PMID- 23950909
TI  - Evaluation of a Salmonella vectored vaccine expressing Mycobacterium avium subsp.
      paratuberculosis antigens against challenge in a goat model.
AB  - Johnes disease (JD), caused by Mycobacterium avium subsp paratuberculosis (MAP),
      occurs worldwide as chronic granulomatous enteritis of domestic and wild
      ruminants. To develop a cost effective vaccine, in a previous study we
      constructed an attenuated Salmonella strain that expressed a fusion product made
      up of partial fragments of MAP antigens (Ag85A, Ag85B and SOD) that imparted
      protection against challenge in a mouse model. In the current study we evaluated
      the differential immune response and protective efficacy of the Sal-Ag vaccine
      against challenge in a goat model as compared to the live attenuated vaccine
      MAP316F. PBMCs from goats vaccinated with Sal-Ag and challenged with MAP
      generated significantly lower levels of IFN-gamma, following in vitro stimulation
      with either Antigen-mix or PPD jhonin, than PBMC from MAP316F vaccinated animals.
      Flow cytometric analysis showed the increase in IFN-gamma correlated with a
      significantly higher level of proliferation of CD4, CD8 and gammadeltaT cells and
      an increased expression of CD25 and CD45R0 in MAP316F vaccinated animals as
      compared to control animals. Evaluation of a range of cytokines involved in Th1,
      Th2, Treg, and Th17 immune responses by quantitative PCR showed low levels of
      expression of Th1 (IFN-gamma, IL-2, IL-12) and proinflammatory cytokines (IL-6,
      IL-8, IL-18, TNF-alpha) in the Sal-Ag immunized group. Significant levels of Th2
      and anti-inflammatory cytokines transcripts (IL-4, IL-10, IL-13, TGF-beta) were
      expressed but their level was low and with a pattern similar to the control
      group. Over all, Sal-Ag vaccine imparted partial protection that limited
      colonization in tissues of some animals upon challenge with wild type MAP but not
      to the level achieved with MAP316F. In conclusion, the data indicates that Sal-Ag
      vaccine induced only a low level of protective immunity that failed to limit the
      colonization of MAP in infected animals. Hence the Sal-Ag vaccine needs further
      refinement to increase its efficacy. 

PMID- 23950911
TI  - Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis
      lung disease.
AB  - RATIONALE: TGF-beta, a mediator of pulmonary fibrosis, is a genetic modifier of
      CF respiratory deterioration. The mechanistic relationship between TGF-beta
      signaling and CF lung disease has not been determined. OBJECTIVE: To investigate
      myofibroblast differentiation in CF lung tissue as a novel pathway by which TGF
      beta signaling may contribute to pulmonary decline, airway remodeling and tissue
      fibrosis. METHODS: Lung samples from CF and non-CF subjects were analyzed
      morphometrically for total TGF-beta1, TGF-beta signaling (Smad2 phosphorylation),
      myofibroblast differentiation (alpha-smooth muscle actin), and collagen
      deposition (Masson trichrome stain). RESULTS: TGF-beta signaling and fibrosis are
      markedly increased in CF (p<0.01), and the presence of myofibroblasts is four
      fold higher in CF vs. normal lung tissue (p<0.005). In lung tissue with prominent
      TGF-beta signaling, both myofibroblast differentiation and tissue fibrosis are
      significantly augmented (p<0.005). CONCLUSIONS: These studies establish for the
      first time that a pathogenic mechanism described previously in pulmonary fibrosis
      is also prominent in cystic fibrosis lung disease. The presence of TGF-beta
      dependent signaling in areas of prominent myofibroblast proliferation and
      fibrosis in CF suggests that strategies under development for other pro-fibrotic
      lung conditions may also be evaluated for use in CF.

PMID- 23950912
TI  - Prediction of microRNAs associated with human diseases based on weighted k most
      similar neighbors.
AB  - BACKGROUND: The identification of human disease-related microRNAs (disease
      miRNAs) is important for further investigating their involvement in the
      pathogenesis of diseases. More experimentally validated miRNA-disease
      associations have been accumulated recently. On the basis of these associations,
      it is essential to predict disease miRNAs for various human diseases. It is
      useful in providing reliable disease miRNA candidates for subsequent experimental
      studies. METHODOLOGY/PRINCIPAL FINDINGS: It is known that miRNAs with similar
      functions are often associated with similar diseases and vice versa. Therefore,
      the functional similarity of two miRNAs has been successfully estimated by
      measuring the semantic similarity of their associated diseases. To effectively
      predict disease miRNAs, we calculated the functional similarity by incorporating
      the information content of disease terms and phenotype similarity between
      diseases. Furthermore, the members of miRNA family or cluster are assigned higher
      weight since they are more probably associated with similar diseases. A new
      prediction method, HDMP, based on weighted k most similar neighbors is presented
      for predicting disease miRNAs. Experiments validated that HDMP achieved
      significantly higher prediction performance than existing methods. In addition,
      the case studies examining prostatic neoplasms, breast neoplasms, and lung
      neoplasms, showed that HDMP can uncover potential disease miRNA candidates.
      CONCLUSIONS: The superior performance of HDMP can be attributed to the accurate
      measurement of miRNA functional similarity, the weight assignment based on miRNA
      family or cluster, and the effective prediction based on weighted k most similar
      neighbors. The online prediction and analysis tool is freely available at
      http://nclab.hit.edu.cn/hdmpred.

PMID- 23950913
TI  - Phylogenetic characterization of beta-tubulins and development of pyrosequencing
      assays for benzimidazole resistance in cattle nematodes.
AB  - Control of helminth infections is a major task in livestock production to prevent
      health constraints and economic losses. However, resistance to established
      anthelmintic substances already impedes effective anthelmintic treatment in many
      regions worldwide. Thus, there is an obvious need for sensitive and reliable
      methods to assess the resistance status of at least the most important nematode
      populations. Several single nucleotide polymorphisms (SNPs) in the beta-tubulin
      isotype 1 gene of various nematodes correlate with resistance to benzimidazoles
      (BZ), a major anthelmintic class. Here we describe the full-length beta-tubulin
      isotype 1 and 2 and alpha-tubulin coding sequences of the cattle nematode
      Ostertagia ostertagi. Additionally, the Cooperia oncophora alpha-tubulin coding
      sequence was identified. Phylogenetic maximum-likelihood analysis revealed that
      both isotype 1 and 2 are orthologs to the Caenorhabditis elegans ben-1 gene which
      is also associated with BZ resistance upon mutation. In contrast, a Trichuris
      trichiura cDNA, postulated to be beta-tubulin isotype 1 involved in BZ resistance
      in this human parasite, turned out to be closely related to C. elegans beta
      tubulins tbb-4 and mec-7 and would therefore represent the first non-ben-1-like
      beta-tubulin to be under selection through treatment with BZs. A pyrosequencing
      assay was established to detect BZ resistance associated SNPs in beta-tubulin
      isotype 1 codons 167, 198 and 200 of C. oncophora and O. ostertagi. PCR-fragments
      representing either of the two alleles were combined in defined ratios to
      evaluate the pyrosequencing assay. The correlation between the given and the
      measured allele frequencies of the respective SNPs was very high. Subsequently
      laboratory isolates and field populations with known resistance status were
      analyzed. With the exception of codon 167 in Cooperia, increases of resistance
      associated alleles were detected for all codons in at least one of the
      phenotypically resistant population. Pyrosequencing provides a fast, inexpensive
      and sensitive alternative to conventional resistance detection methods. 

PMID- 23950914
TI  - Associations between night work and anxiety, depression, insomnia, sleepiness and
      fatigue in a sample of Norwegian nurses.
AB  - BACKGROUND: Night work has been reported to be associated with various mental
      disorders and complaints. We investigated relationships between night work and
      anxiety, depression, insomnia, sleepiness and fatigue among Norwegian nurses.
      METHODS: The study design was cross-sectional, based on validated self-assessment
      questionnaires. A total of 5400 nurses were invited to participate in a health
      survey through the Norwegian Nurses' Organization, whereof 2059 agreed to
      participate (response rate 38.1%). Nurses completed a questionnaire containing
      items on demographic variables (gender, age, years of experience as a nurse,
      marital status and children living at home), work schedule, anxiety/depression
      (Hospital Anxiety and Depression Scale), insomnia (Bergen Insomnia Scale),
      sleepiness (Epworth Sleepiness Scale) and fatigue (Fatigue Questionnaire). They
      were also asked to report number of night shifts in the last 12 months (NNL).
      First, the parameters were compared between nurses i) never working nights, ii)
      currently working nights, and iii) previously working nights, using binary
      logistic regression analyses. Subsequently, a cumulative approach was used
      investigating associations between NNL with the continuous scores on the same
      dependent variables in hierarchical multiple regression analyses. RESULTS: Nurses
      with current night work were more often categorized with insomnia (OR = 1.48, 95%
      CI = 1.10-1.99) and chronic fatigue (OR = 1.78, 95% CI = 1.02-3.11) than nurses
      with no night work experience. Previous night work experience was also associated
      with insomnia (OR = 1.45, 95% CI = 1.04-2.02). NNL was not associated with any
      parameters in the regression analyses. CONCLUSION: Nurses with current or
      previous night work reported more insomnia than nurses without any night work
      experience, and current night work was also associated with chronic fatigue.
      Anxiety, depression and sleepiness were not associated with night work, and no
      cumulative effect of night shifts during the last 12 months was found on any
      parameters.

PMID- 23950915
TI  - Development of RNAi methods for Peregrinus maidis, the corn planthopper.
AB  - The corn planthopper, Peregrinus maidis, is a major pest of agronomically
      important crops. Peregrinus maidis has a large geographical distribution and
      transmits Maize mosaic rhabdovirus (MMV) and Maize stripe tenuivirus (MSpV). The
      objective of this study was to develop effective RNAi methods for P. maidis.
      Vacuolar-ATPase (V-ATPase) is an essential enzyme for hydrolysis of ATP and for
      transport of protons out of cells thereby maintaining membrane ion balance, and
      it has been demonstrated to be an efficacious target for RNAi in other insects.
      In this study, two genes encoding subunits of P. maidis V-ATPase (V-ATPase B and
      V-ATPase D) were chosen as RNAi target genes. The open reading frames of V-ATPase
      B and D were generated and used for constructing dsRNA fragments. Experiments
      were conducted using oral delivery and microinjection of V-ATPase B and V-ATPase
      D dsRNA to investigate the effectiveness of RNAi in P. maidis. Real-time
      quantitative reverse transcriptase-PCR (qRT-PCR) analysis indicated that
      microinjection of V-ATPase dsRNA led to a minimum reduction of 27-fold in the
      normalized abundance of V-ATPase transcripts two days post injection, while
      ingestion of dsRNA resulted in a two-fold reduction after six days of feeding.
      While both methods of dsRNA delivery resulted in knockdown of target transcripts,
      the injection method was more rapid and effective. The reduction in V-ATPase
      transcript abundance resulted in observable phenotypes. Specifically, the
      development of nymphs injected with 200 ng of either V-ATPase B or D dsRNA was
      impaired, resulting in higher mortality and lower fecundity than control insects
      injected with GFP dsRNA. Microscopic examination of these insects revealed that
      female reproductive organs did not develop normally. The successful development
      of RNAi in P. maidis to target specific genes will enable the development of new
      insect control strategies and functional analysis of vital genes and genes
      associated with interactions between P. maidis and MMV. 

PMID- 23950916
TI  - Long-term artificial sweetener acesulfame potassium treatment alters
      neurometabolic functions in C57BL/6J mice.
AB  - With the prevalence of obesity, artificial, non-nutritive sweeteners have been
      widely used as dietary supplements that provide sweet taste without excessive
      caloric load. In order to better understand the overall actions of artificial
      sweeteners, especially when they are chronically used, we investigated the
      peripheral and central nervous system effects of protracted exposure to a widely
      used artificial sweetener, acesulfame K (ACK). We found that extended ACK
      exposure (40 weeks) in normal C57BL/6J mice demonstrated a moderate and limited
      influence on metabolic homeostasis, including altering fasting insulin and leptin
      levels, pancreatic islet size and lipid levels, without affecting insulin
      sensitivity and bodyweight. Interestingly, impaired cognitive memory functions
      (evaluated by Morris Water Maze and Novel Objective Preference tests) were found
      in ACK-treated C57BL/6J mice, while no differences in motor function and anxiety
      levels were detected. The generation of an ACK-induced neurological phenotype was
      associated with metabolic dysregulation (glycolysis inhibition and functional ATP
      depletion) and neurosynaptic abnormalities (dysregulation of TrkB-mediated BDNF
      and Akt/Erk-mediated cell growth/survival pathway) in hippocampal neurons. Our
      data suggest that chronic use of ACK could affect cognitive functions,
      potentially via altering neuro-metabolic functions in male C57BL/6J mice. 

PMID- 23950918
TI  - Investigating the effects of exam length on performance and cognitive fatigue.
AB  - This study examined the effects of exam length on student performance and
      cognitive fatigue in an undergraduate biology classroom. Exams tested higher
      order thinking skills. To test our hypothesis, we administered standard- and
      extended-length high-level exams to two populations of non-majors biology
      students. We gathered exam performance data between conditions as well as
      performance on the first and second half of exams within conditions. We showed
      that lengthier exams led to better performance on assessment items shared between
      conditions, possibly lending support to the spreading activation theory. It also
      led to greater performance on the final exam, lending support to the testing
      effect in creative problem solving. Lengthier exams did not result in lower
      performance due to fatiguing conditions, although students perceived subjective
      fatigue. Implications of these findings are discussed with respect to assessment
      practices. 

PMID- 23950917
TI  - Thioredoxin-1 attenuates early graft loss after intraportal islet transplantation
      in mice.
AB  - AIMS: Recent studies suggest that decreasing oxidative stress is crucial to
      achieve successful islet transplantation. Thioredoxin-1 (TRX), which is a
      multifunctional redox-active protein, has been reported to suppress oxidative
      stress. Furthermore, it also has anti-inflammatory and anti-apoptotic effects. In
      this study, we investigated the effects of TRX on early graft loss after islet
      transplantation. METHODS: Intraportal islet transplantation was performed for two
      groups of streptozotocin-induced diabetic mice: a control and a TRX group. In
      addition, TRX-transgenic (Tg) mice were alternately used as islet donors or
      recipients. RESULTS: The changes in blood glucose levels were significantly lower
      in the TRX group compared with the TRX-Tg donor and control groups (p<0.01).
      Glucose tolerance and the residual graft mass were considerably better in the TRX
      group. TRX significantly suppressed the serum levels of interleukin-1beta
      (p<0.05), although neither anti-apoptotic nor anti-chemotactic effects were
      observed. Notably, no increase in the 8-hydroxy-2'-deoxyguanosine level was
      observed after islet infusion, irrespective of TRX administration. CONCLUSIONS:
      The present study demonstrates that overexpression of TRX on the islet grafts is
      not sufficient to improve engraftment. In contrast, TRX administration to the
      recipients exerts protective effects on transplanted islet grafts by suppressing
      the serum levels of interleukin-1beta. However, TRX alone appears to be
      insufficient to completely prevent early graft loss after islet transplantation.
      We therefore propose that a combination of TRX and other anti-inflammatory
      treatments represents a promising regimen for improving the efficacy of islet
      transplantation.

PMID- 23950919
TI  - Habitual chocolate consumption may increase body weight in a dose-response
      manner.
AB  - OBJECTIVE: Habitual chocolate intake was recently found to be associated with
      lower body weight in three cross-sectional epidemiological studies. Our objective
      was to assess whether these cross-sectional results hold up in a more rigorous
      prospective analysis. METHODS: We used data from the Atherosclerosis Risk in
      Communities cohort. Usual dietary intake was assessed by questionnaire at
      baseline (1987-98), and after six years. Participants reported usual chocolate
      intake as the frequency of eating a 1-oz (~28 g) serving. Body weight and height
      were measured at the two visits. Missing data were replaced by multiple
      imputation. Linear mixed-effects models were used to evaluate cross-sectional and
      prospective associations between chocolate intake and adiposity. RESULTS: Data
      were from 15,732 and 12,830 participants at the first and second visit,
      respectively. More frequent chocolate consumption was associated with a
      significantly greater prospective weight gain over time, in a dose-response
      manner. For instance, compared to participants who ate a chocolate serving less
      often than monthly, those who ate it 1-4 times a month and at least weekly
      experienced an increase in Body Mass Index (kg/m2) of 0.26 (95% CI 0.08, 0.44)
      and 0.39 (0.23, 0.55), respectively, during the six-year study period. In cross
      sectional analyses the frequency of chocolate consumption was inversely
      associated with body weight. This inverse association was attenuated after
      excluding participants with preexisting obesity-related illness. Compared to
      participants without such illness, those with it had higher BMI and reported less
      frequent chocolate intake, lower caloric intake, and diets richer in fruits and
      vegetables. They tended to make these dietary changes after becoming ill.
      CONCLUSIONS: Our prospective analysis found that a chocolate habit was associated
      with long-term weight gain, in a dose-response manner. Our cross-sectional
      finding that chocolate intake was associated with lower body weight did not apply
      to participants without preexisting serious illness.

PMID- 23950920
TI  - Is adding HCV screening to the antenatal national screening program in Amsterdam,
      the Netherlands, cost-effective?
AB  - INTRODUCTION: Hepatitis C virus (HCV) infection can lead to severe liver disease.
      Pregnant women are already routinely screened for several infectious diseases,
      but not yet for HCV infection. Here we examine whether adding HCV screening to
      routine screening is cost-effective. METHODS: To estimate the cost-effectiveness
      of implementing HCV screening of all pregnant women and HCV screening of first
      generation non-Western pregnant women as compared to no screening, we developed a
      Markov model. For the parameters of the model, we used prevalence data from
      pregnant women retrospectively tested for HCV in Amsterdam, the Netherlands, and
      from literature sources. In addition, we estimated the effect of possible
      treatment improvement in the future. RESULTS: The incremental costs per woman
      screened was ?41 and 0.0008 life-years were gained. The incremental cost
      effectiveness ratio (ICER) was ?52,473 which is above the cost-effectiveness
      threshold of ?50,000. For screening first-generation non-Western migrants, the
      ICER was ?47,113. Best-case analysis for both scenarios showed ICERs of
      respectively ?19,505 and ?17,533. We estimated that if costs per treatment were
      to decline to ?3,750 (a reduction in price of ?31,000), screening all pregnant
      women would be cost-effective. CONCLUSIONS: Currently, adding HCV screening to
      the already existing screening program for pregnant women is not cost-effective
      for women in general. However, adding HCV screening for first-generation non
      Western women shows a modest cost-effective outcome. Yet, best case analysis
      shows potentials for an ICER below ?20,000 per life-year gained. Treatment
      options will improve further in the coming years, enhancing cost-effectiveness
      even more.

PMID- 23950921
TI  - Real-time strategy game training: emergence of a cognitive flexibility trait.
AB  - Training in action video games can increase the speed of perceptual processing.
      However, it is unknown whether video-game training can lead to broad-based
      changes in higher-level competencies such as cognitive flexibility, a core and
      neurally distributed component of cognition. To determine whether video gaming
      can enhance cognitive flexibility and, if so, why these changes occur, the
      current study compares two versions of a real-time strategy (RTS) game. Using a
      meta-analytic Bayes factor approach, we found that the gaming condition that
      emphasized maintenance and rapid switching between multiple information and
      action sources led to a large increase in cognitive flexibility as measured by a
      wide array of non-video gaming tasks. Theoretically, the results suggest that the
      distributed brain networks supporting cognitive flexibility can be tuned by
      engrossing video game experience that stresses maintenance and rapid manipulation
      of multiple information sources. Practically, these results suggest avenues for
      increasing cognitive function. 

PMID- 23950922
TI  - Carnivora population dynamics are as slow and as fast as those of other mammals:
      implications for their conservation.
AB  - Of the 285 species of Carnivora 71 are threatened, while many of these species
      fulfill important ecological roles in their ecosystems as top or meso-predators.
      Population transition matrices make it possible to study how age-specific
      survival and fecundity affect population growth, extinction risks, and responses
      to management strategies. Here we review 38 matrix models from 35 studies on 27
      Carnivora taxa, covering 11% of the threatened Carnivora species. We show that
      the elasticity patterns (i.e. distribution over fecundity, juvenile survival and
      adult survival) in Carnivora cover the same range in triangular elasticity plots
      as those of other mammal species, despite the specific place of Carnivora in the
      food chain. Furthermore, reproductive loop elasticity analysis shows that the
      studied species spread out evenly over a slow-fast continuum, but also quantifies
      the large variation in the duration of important life cycles and their
      contributions to population growth rate. These general elasticity patterns among
      species, and their correlation with simple life history characteristics like body
      mass, age of first reproduction and life span, enables the extrapolation of
      population dynamical properties to unstudied species. With several examples we
      discuss how this slow-fast continuum, and related patterns of variation in
      reproductive loop elasticity, can be used in the formulation of tentative
      management plans for threatened species that cannot wait for the results of
      thorough demographic studies. We argue, however, that such management programs
      should explicitly include a plan for learning about the key demographic rates and
      how these are affected by environmental drivers and threats. 

PMID- 23950923
TI  - Metal ion concentrations in body fluids after implantation of hip replacements
      with metal-on-metal bearing--systematic review of clinical and epidemiological
      studies.
AB  - INTRODUCTION: The use of metal-on-metal (MoM) total hip arthroplasty (THA)
      increased in the last decades. A release of metal products (i.e. particles, ions,
      metallo-organic compounds) in these implants may cause local and/or systemic
      adverse reactions. Metal ion concentrations in body fluids are surrogate measures
      of metal exposure. OBJECTIVE: To systematically summarize and critically appraise
      published studies concerning metal ion concentrations after MoM THA. METHODS:
      Systematic review of clinical trials (RCTs) and epidemiological studies with
      assessment of metal ion levels (cobalt, chromium, titanium, nickel, molybdenum)
      in body fluids after implantation of metalliferous hip replacements. Systematic
      search in PubMed and Embase in January 2012 supplemented by hand search.
      Standardized abstraction of pre- and postoperative metal ion concentrations
      stratified by type of bearing (primary explanatory factor), patient
      characteristics as well as study quality characteristics (secondary explanatory
      factors). RESULTS: Overall, 104 studies (11 RCTs, 93 epidemiological studies)
      totaling 9.957 patients with measurement of metal ions in body fluids were
      identified and analyzed. Consistently, median metal ion concentrations were
      persistently elevated after implantation of MoM-bearings in all investigated
      mediums (whole blood, serum, plasma, erythrocytes, urine) irrespective of patient
      characteristics and study characteristics. In several studies very high serum
      cobalt concentrations above 50 ug/L were measured (detection limit typically 0.3
      ug/L). Highest metal ion concentrations were observed after treatment with
      stemmed large-head MoM-implants and hip resurfacing arthroplasty. DISCUSSION: Due
      to the risk of local and systemic accumulation of metallic products after
      treatment with MoM-bearing, risk and benefits should be carefully balanced
      preoperatively. The authors support a proposed "time out" for stemmed large-head
      MoM-THA and recommend a restricted indication for hip resurfacing arthroplasty.
      Patients with implanted MoM-bearing should receive regular and standardized
      monitoring of metal ion concentrations. Further research is indicated especially
      with regard to potential systemic reactions due to accumulation of metal
      products.

PMID- 23950924
TI  - Early experience after developing a pathology laboratory in Malawi, with emphasis
      on cancer diagnoses.
AB  - BACKGROUND: Despite increasing cancer burden in Malawi, pathology services are
      limited. We describe operations during the first 20 months of a new pathology
      laboratory in Lilongwe, with emphasis on cancer diagnoses. METHODS AND FINDINGS:
      We performed a cross-sectional study of specimens from the Kamuzu Central
      Hospital pathology laboratory between July 1, 2011 and February 28, 2013. Patient
      and specimen characteristics, and final diagnoses are summarized. Diagnoses were
      categorized as malignant, premalignant, infectious, other pathology, normal or
      benign, or nondiagnostic. Patient characteristics associated with premalignancy
      and malignancy were assessed using logistic regression. Of 2772 specimens, 2758
      (99%) with a recorded final diagnosis were included, drawn from 2639 unique
      patients. Mean age was 38 years and 63% were female. Of those with documented HIV
      status, 51% had unknown status, and 36% with known status were infected.
      Histologic specimens comprised 91% of cases, and cytologic specimens 9%.
      Malignant diagnoses were most common overall (n = 861, 31%). Among cancers,
      cervical cancer was most common (n = 117, 14%), followed by lymphoma (n = 91,
      11%), esophageal cancer (n = 86, 10%), sarcoma excluding Kaposi sarcoma (n = 75,
      9%), and breast cancer (n = 61, 7%). HIV status was known for 95 (11%) of
      malignancies, with HIV prevalence ranging from 9% for breast cancer to 81% for
      cervical cancer. Increasing age was consistently associated with malignancy
      [bivariable odds ratio 1.24 per decade increase (95% CI 1.19-1.29) among 2685
      patients with known age; multivariable odds ratio 1.33 per decade increase (95%
      CI 1.14-1.56) among 317 patients with known age, gender, and HIV status], while
      HIV infection and gender were not. CONCLUSIONS: Despite selection and referral
      bias inherent in these data, a new pathology laboratory in Lilongwe has created a
      robust platform for cancer care and research. Strategies to effectively capture
      clinical information for pathologically confirmed cancers can allow these data to
      complement population-based registration.

PMID- 23950925
TI  - WIP regulates persistence of cell migration and ruffle formation in both
      mesenchymal and amoeboid modes of motility.
AB  - The spatial distribution of signals downstream from receptor tyrosine kinases
      (RTKs) or G-protein coupled receptors (GPCR) regulates fundamental cellular
      processes that control cell migration and growth. Both pathways rely
      significantly on actin cytoskeleton reorganization mediated by nucleation
      promoting factors such as the WASP-(Wiskott-Aldrich Syndrome Protein) family. WIP
      (WASP Interacting Protein) is essential for the formation of a class of polarised
      actin microdomain, namely dorsal ruffles, downstream of the RTK for PDGF
      (platelet-derived growth factor) but the underlying mechanism is poorly
      understood. Using lentivirally-reconstituted WIP-deficient murine fibroblasts we
      define the requirement for WIP interaction with N-WASP (neural WASP) and Nck for
      efficient dorsal ruffle formation and of WIP-Nck binding for fibroblast
      chemotaxis towards PDGF-AA. The formation of both circular dorsal ruffles in PDGF
      AA-stimulated primary fibroblasts and lamellipodia in CXCL13-treated B
      lymphocytes are also compromised by WIP-deficiency. We provide data to show that
      a WIP-Nck signalling complex interacts with RTK to promote polarised actin
      remodelling in fibroblasts and provide the first evidence for WIP involvement in
      the control of migratory persistence in both mesenchymal (fibroblast) and
      amoeboid (B lymphocytes) motility. 

PMID- 23950926
TI  - Geographic variation in the acoustic traits of greater horseshoe bats: testing
      the importance of drift and ecological selection in evolutionary processes.
AB  - Patterns of intraspecific geographic variation of signaling systems provide
      insight into the microevolutionary processes driving phenotypic divergence. The
      acoustic calls of bats are sensitive to diverse evolutionary forces, but
      processes that shape call variation are largely unexplored. In China, Rhinolophus
      ferrumequinum displays a diverse call frequency and inhabits a heterogeneous
      landscape, presenting an excellent opportunity for this kind of research. We
      quantified geographic variation in resting frequency (RF) of echolocation calls,
      estimated genetic structure and phylogeny of R. ferrumequinum populations, and
      combined this with climatic factors to test three hypotheses to explain acoustic
      variation: genetic drift, cultural drift, and local adaptation. Our results
      demonstrated significant regional divergence in frequency and phylogeny among the
      bat populations in China's northeast (NE), central-east (CE) and southwest (SW)
      regions. The CE region had higher frequencies than the NE and SW regions. Drivers
      of RF divergence were estimated in the entire range and just the CE/NE region
      (since these two regions form a clade). In both cases, RF divergence was not
      correlated with mtDNA or nDNA genetic distance, but was significantly correlated
      with geographic distance and mean annual temperature, indicating cultural drift
      and ecological selection pressures are likely important in shaping RF divergence
      among different regions in China. 

PMID- 23950927
TI  - Estuaries as filters: the role of tidal marshes in trace metal removal.
AB  - Flux calculations demonstrate that many estuaries are natural filters for trace
      metals. Yet, the underlying processes are poorly investigated. In the present
      study, it was hypothesized that intertidal marshes contribute significantly to
      the contaminant filter function of estuaries. Trace metal concentrations and
      sediment characteristics were measured along a transect from the subtidal, over
      an intertidal flat and marsh to a restored marsh with controlled reduced tide.
      Metal concentrations in the intertidal and restored marsh were found to be a
      factor two to five higher than values in the subtidal and intertidal flat
      sediments. High metal concentrations and high accretion rates indicate a high
      metal accumulation capacity of the intertidal marshes. Overbank sedimentation in
      the tidal marshes of the entire estuary was calculated to remove 25% to 50% of
      the riverine metal influx, even though marshes comprise less than 8% of the total
      surface of the estuary. In addition, the large-scale implementation of planned
      tidal marsh restoration projects was estimated to almost double the trace metal
      storage capacity of the present natural tidal marshes in the estuary. 

PMID- 23950928
TI  - Link between epigenomic alterations and genome-wide aberrant transcriptional
      response to allergen in dendritic cells conveying maternal asthma risk.
AB  - We investigated the link between epigenome-wide methylation aberrations at birth
      and genomic transcriptional changes upon allergen sensitization that occur in the
      neonatal dendritic cells (DC) due to maternal asthma. We previously demonstrated
      that neonates of asthmatic mothers are born with a functional skew in splenic DCs
      that can be seen even in allergen-naive pups and can convey allergy responses to
      normal recipients. However, minimal-to-no transcriptional or phenotypic changes
      were found to explain this alteration. Here we provide in-depth analysis of
      genome-wide DNA methylation profiles and RNA transcriptional (microarray)
      profiles before and after allergen sensitization. We identified differentially
      methylated and differentially expressed loci and performed manually-curated
      matching of methylation status of the key regulatory sequences (promoters and CpG
      islands) to expression of their respective transcripts before and after
      sensitization. We found that while allergen-naive DCs from asthma-at-risk
      neonates have minimal transcriptional change compared to controls, the
      methylation changes are extensive. The substantial transcriptional change only
      becomes evident upon allergen sensitization, when it occurs in multiple genes
      with the pre-existing epigenetic alterations. We demonstrate that maternal asthma
      leads to both hyper- and hypomethylation in neonatal DCs, and that both types of
      events at various loci significantly overlap with transcriptional responses to
      allergen. Pathway analysis indicates that approximately 1/2 of differentially
      expressed and differentially methylated genes directly interact in known networks
      involved in allergy and asthma processes. We conclude that congenital epigenetic
      changes in DCs are strongly linked to altered transcriptional responses to
      allergen and to early-life asthma origin. The findings are consistent with the
      emerging paradigm that asthma is a disease with underlying epigenetic changes. 

PMID- 23950930
TI  - The conservation and management of tunas and their relatives: setting life
      history research priorities.
AB  - Scombrids (tunas, bonitos, Spanish mackerels and mackerels) support important
      fisheries in tropical, subtropical and temperate waters around the world, being
      one of the most economically- and socially-important marine species globally.
      Their sustainable exploitation, management and conservation depend on accurate
      life history information for the development of quantitative fisheries stock
      assessments, and in the fishery data-poor situations for the identification of
      vulnerable species. Here, we assemble life history traits (maximum size, growth,
      longevity, maturity, fecundity, spawning duration and spawning interval) for the
      51 species of scombrids globally. We identify major biological gaps in knowledge
      and prioritize life history research needs in scombrids based on their biological
      gaps in knowledge, the importance of their fisheries and their current
      conservation status according to the International Union for Conservation of
      Nature Red List. We find that the growth and reproductive biology of tunas and
      mackerel species have been more extensively studied than for Spanish mackerels
      and bonitos, although there are notable exceptions in all groups. We also reveal
      that reproductive biology of species, particular fecundity, is the least studied
      biological aspect in scombrids. We identify two priority groups, including 32
      species of scombrids, and several populations of principal market tunas, for
      which life history research should be prioritized following the species-specific
      life history gaps identified in this study in the coming decades. By highlighting
      the important gaps in biological knowledge and providing a priority setting for
      life history research in scombrid species this study provides guidance for
      management and conservation and serves as a guide for biologists and resource
      managers interested in the biology, ecology, and management of scombrid species. 

PMID- 23950929
TI  - The transmembrane protein of the human endogenous retrovirus--K (HERV-K)
      modulates cytokine release and gene expression.
AB  - Numerous copies of endogenous retroviruses are present in the genome of mammals
      including man. Although most of them are defective, some, e.g., the human
      endogenous retroviruses HERV-K, were found to be expressed under certain
      physiological conditions. For instance, HERV-K is expressed in germ cell tumours
      and melanomas as well as in the placenta. Most exogenous retroviruses including
      the human immunodeficiency virus HIV-1 induce severe immunodeficiencies and there
      is increasing evidence that the transmembrane envelope (TM) proteins of these
      retroviruses may be involved. We show here that HERV-K particles released from a
      human teratocarcinoma cell line, a recombinant TM protein and a peptide
      corresponding to a highly conserved so-called immunosuppressive domain in the TM
      protein of HERV-K inhibit the proliferation of human immune cells, induce
      modulation of the expression of numerous cytokines, and modulate the expression
      of cellular genes as detected by a microarray analysis. The changes in cytokine
      release and gene expression induced by the TM protein of HERV-K are similar to
      those found previously induced by the TM protein of HIV-1. These data suggest
      that the mechanism of immunosuppression may be similar for different retroviruses
      and that the expression of the TM protein in tumours and in the placenta may
      suppress immune responses and thus prevent rejection of the tumour and the
      embryo. 

PMID- 23950931
TI  - RNAi mediated Tiam1 gene knockdown inhibits invasion of retinoblastoma.
AB  - T lymphoma invasion and metastasis protein (Tiam1) is up-regulated in variety of
      cancers and its expression level is related to metastatic potential of the type
      of cancer. Earlier, Tiam1 was shown to be overexpressed in retinoblastoma (RB)
      and we hypothesized that it was involved in invasiveness of RB. This was tested
      by silencing Tiam1 in RB cell lines (Y79 and Weri-Rb1) using siRNA pool,
      targeting different regions of Tiam1 mRNA. The cDNA microarray of Tiam1 silenced
      cells showed gene regulations altered by Tiam1 were predominantly on the actin
      cytoskeleton interacting proteins, apoptotic initiators and tumorogenic potential
      targets. The silenced phenotype resulted in decreased growth and increased
      apoptosis with non-invasive characteristics. Transfection of full length and N
      terminal truncated construct (C1199) clearly revealed membrane localization of
      Tiam1 and not in the case of C580 construct. F-actin staining showed the
      interaction of Tiam1 with actin in the membrane edges that leads to ruffling, and
      also imparts varying invasive potential to the cell. The results obtained from
      our study show for the first time that Tiam1 modulates the cell invasion,
      mediated by actin cytoskeleton remodeling in RB. 

PMID- 23950932
TI  - EMT-induced stemness and tumorigenicity are fueled by the EGFR/Ras pathway.
AB  - Recent studies have revealed that differentiated epithelial cells would acquire
      stem cell-like and tumorigenic properties following an Epithelial-Mesenchymal
      Transition (EMT). However, the signaling pathways that participate in this novel
      mechanism of tumorigenesis have not been fully characterized. In Runx3 (-/-) p53
      (-/-) murine gastric epithelial (GIF-14) cells, EMT-induced plasticity is
      reflected in the expression of the embryonal proto-oncogene Hmga2 and Lgr5, an
      exclusive gastrointestinal stem cell marker. Here, we report the concurrent
      activation of an EGFR/Ras gene expression signature during TGF-beta1-induced EMT
      in GIF-14 cells. Amongst the altered genes was the induction of Egfr, which
      corresponded with a delayed sensitization to EGF treatment in GIF-14. Co
      treatment with TGF-beta1 and EGF or the expression of exogenous KRas led to
      increased Hmga2 or Lgr5 expression, sphere initiation and colony formation in
      soft agar assay. Interestingly, the gain in cellular plasticity/tumorigenicity
      was not accompanied by increased EMT. This uncoupling of EMT and the induction of
      plasticity reveals an involvement of distinct signaling cues, whereby the
      EGFR/Ras pathway specifically promotes stemness and tumorigenicity in EMT-altered
      GIF-14 cells. These data show that the EGFR/Ras pathway requisite for the
      sustenance of gastric stem cells in vivo and in vitro is involved in the genesis
      and promotion of EMT-induced tumor-initiating cells. 

PMID- 23950933
TI  - Identification and validation of a multigene predictor of recurrence in primary
      laryngeal cancer.
AB  - PURPOSE: Local recurrence is the major manifestation of treatment failure in
      patients with operable laryngeal carcinoma. Established clinicopathological
      factors cannot sufficiently predict patients that are likely to recur after
      treatment. Additional tools are therefore required to accurately identify
      patients at high risk for recurrence. This study attempts to identify and
      independently validate gene expression models, prognostic of disease-free
      survival (DFS) in operable laryngeal cancer. MATERIALS AND METHODS: Using
      Affymetrix U133A Genechips, we profiled fresh-frozen tumor tissues from 66
      patients with laryngeal cancer treated locally with surgery. We applied Cox
      regression proportional hazards modeling to identify multigene predictors of
      recurrence. Gene models were then validated in two independent cohorts of 54 and
      187 patients (fresh-frozen and formalin-fixed tissue validation sets,
      respectively). RESULTS: We focused on genes univariately associated with DFS
      (p<0.01) in the training set. Among several models comprising different numbers
      of genes, a 30-probe set model demonstrated optimal performance in both the
      training (log-rank, p<0.001) and 1(st) validation (p=0.010) sets. Specifically,
      in the 1(st) validation set, median DFS as predicted by the 30-probe set model,
      was 34 and 80 months for high- and low-risk patients, respectively. Hazard ratio
      (HR) for recurrence in the high-risk group was 3.87 (95% CI 1.28-11.73, Wald's
      p=0.017). Testing the expression of selected genes from the above model in the
      2(nd) validation set, with qPCR, revealed significant associations of single
      markers, such as ACE2, FLOT1 and PRKD1, with patient DFS. High PRKD1 remained an
      unfavorable prognostic marker upon multivariate analysis (HR=2.00, 95% CI 1.28
      3.14, p=0.002) along with positive nodal status. CONCLUSIONS: We have established
      and validated gene models that can successfully stratify patients with laryngeal
      cancer, based on their risk for recurrence. It seems worthy to prospectively
      validate PRKD1 expression as a laryngeal cancer prognostic marker, for routine
      clinical applications.

PMID- 23950934
TI  - Segregation of a latent high adiposity phenotype in families with a history of
      type 2 diabetes mellitus implicates rare obesity-susceptibility genetic variants
      with large effects in diabetes-related obesity.
AB  - BACKGROUND: We recently reported significantly greater weight gain in non
      diabetic healthy subjects with a 1(st) degree family history (FH+) of type 2
      diabetes mellitus (T2DM) than in a matched control group without such history (FH
      ) during voluntary overfeeding, implying co-inheritance of susceptibilities to
      T2DM and obesity. We have estimated the extent and mode of inheritance of
      susceptibility to increased adiposity in FH+. METHODS: Normoglycaemic
      participants were categorised either FH+ (>=1 1(st) degree relative with T2DM, 50
      F/30 M, age 45 +/- 14 (SD) yr) or FH- (71F/51M, age 43 +/- 14 yr). Log
      transformed anthropometric measurements (height, hip and waist circumferences)
      and lean, bone and fat mass (Dual Energy X-ray Absorptiometry) data were analysed
      by rotated Factor Analysis. The age- and gender-adjusted distributions of indices
      of adiposity in FH+ were assessed by fits to a bimodal model and by relative risk
      ratios (RR, FH+/FH-) and interpreted in a purely genetic model of FH effects.
      RESULTS: The two orthogonal factors extracted, interpretable as Frame and
      Adiposity accounted for 80% of the variance in the input data. FH+ was associated
      with significantly higher Adiposity scores (p<0.01) without affecting Frame
      scores. Adiposity scores in FH+ conformed to a bimodal normal distribution,
      consistent with dominant expression of major susceptibility genes with 59% (95%
      CI 40%, 74%) of individuals under the higher mode. Calculated risk allele
      frequencies were 0.09 (0.02, 0.23) in FH-, 0.36 (0.22, 0.48) in FH+ and 0.62
      (0.36, 0.88) in unobserved T2DM-affected family members. CONCLUSIONS: The
      segregation of Adiposity in T2DM-affected families is consistent with dominant
      expression of rare risk variants with major effects, which are expressed in over
      half of FH+ and which can account for most T2DM-associated obesity in our
      population. The calculated risk allele frequency in FH- suggests that rare
      genetic variants could also account for a substantial fraction of the prevalent
      obesity in this society.

PMID- 23950935
TI  - Mechanical stretch increases MMP-2 production in vascular smooth muscle cells via
      activation of PDGFR-beta/Akt signaling pathway.
AB  - Increased blood pressure, leading to mechanical stress on vascular smooth muscle
      cells (VSMC), is a known risk factor for vascular remodeling via increased
      activity of matrix metalloproteinase (MMP) within the vascular wall. This study
      aimed to identify cell surface mechanoreceptors and intracellular signaling
      pathways that influence VSMC to produce MMP in response to mechanical stretch
      (MS). When VSMC was stimulated with MS (0-10% strain, 60 cycles/min), both
      production and gelatinolytic activity of MMP-2, but not MMP-9, were increased in
      a force-dependent manner. MS-enhanced MMP-2 expression and activity were
      inhibited by molecular inhibition of Akt using Akt siRNA as well as by PI3K/Akt
      inhibitors, LY293002 and AI, but not by MAPK inhibitors such as PD98059, SP600125
      and SB203580. MS also increased Akt phosphorylation in VSMC, which was attenuated
      by AG1295, a PDGF receptor (PDGFR) inhibitor, but not by inhibitors for other
      receptor tyrosine kinase including EGF, IGF, and FGF receptors. Although MS
      activated PDGFR-alpha as well as PDGFR-beta in VSMC, MS-induced Akt
      phosphorylation was inhibited by molecular deletion of PDGFR-beta using siRNA,
      but not by inhibition of PDGFR-alpha. Collectively, our data indicate that MS
      induces MMP-2 production in VSMC via activation of Akt pathway, that is mediated
      by activation of PDGFR-beta signaling pathways. 

PMID- 23950936
TI  - Connective tissue growth factor (CTGF) expression modulates response to high
      glucose.
AB  - Connective tissue growth factor (CTGF) is an important mediator of fibrosis;
      emerging evidence link changes in plasma and urinary CTGF levels to diabetic
      kidney disease. To further ascertain the role of CTGF in responses to high
      glucose, we assessed the consequence of 4 months of streptozotocin-induced
      diabetes in wild type (+/+) and CTGF heterozygous (+/-) mice. Subsequently, we
      studied the influence of glucose on gene expression and protein in mice embryonic
      fibroblasts (MEF) cells derived from wildtype and heterozygous mice. At study
      initiation, plasma glucose, creatinine, triglyceride and cholesterol levels were
      similar between non-diabetic CTGF+/+ and CTGF+/- mice. In the diabetic state,
      plasma glucose levels were increased in CTGF+/+ and CTGF+/- mice (28.2 3.3 mmol/L
      vs 27.0 3.1 mmol/L), plasma triglyceride levels were lower in CTGF+/- mice than
      in CTGF+/+ (0.7 0.2 mmol/L vs 0.5 0.1 mmol/L, p<0.05), but cholesterol was
      essentially unchanged in both groups. Plasma creatinine was higher in diabetic
      CTGF+/+ group (11.7+/-1.2 vs 7.9+/-0.6 umol/L p<0.01), while urinary albumin
      excretion and mesangial expansion were reduced in diabetic CTGF+/- animals.
      Cortices from diabetic mice (both CTGF +/+ and CTGF +/-) manifested higher
      expression of CTGF and thrombospondin 1 (TSP1). Expression of nephrin was reduced
      in CTGF +/+ animals; this reduction was attenuated in CTGF+/- group. In cultured
      MEF from CTGF+/+ mice, glucose (25 mM) increased expression of pro-collagens 1,
      IV and XVIII as well as fibronectin and thrombospondin 1 (TSP1). In contrast,
      activation of these genes by high glucose was attenuated in CTGF+/- MEF. We
      conclude that induction of Ctgf mediates expression of extracellular matrix
      proteins in diabetic kidney. Thus, genetic variability in CTGF expression
      directly modulates the severity of diabetic nephropathy. 

PMID- 23950937
TI  - Comorbidities and lack of blood transfusion may negatively affect maternal
      outcomes of women with obstetric hemorrhage treated with NASG.
AB  - The Non-Pneumatic Anti-Shock Garment (NASG) is a first-aid device to reduce
      mortality from severe obstetric hemorrhage, the leading cause of maternal
      mortality globally. We sought to evaluate patient characteristics associated with
      mortality among a cohort of women treated with the NASG in Nigeria. Data on 1,149
      women were collected from 50 facilities participating in the Pathfinder
      International Continuum of Care: Addressing Postpartum Hemorrhage project in
      Nigeria from 2007-2012. Characteristics were compared using the appropriate
      distributional tests, and we estimated multivariable logistic regression models
      to control for treatment received. There were 201 deaths (17.5%). Women who died
      were significantly more likely to have any co-morbidity (AOR 3.63, 95% CI: 2.41
      5.48), ruptured uterus (AOR 2.79, 95% CI: 1.48-5.28), macerated stillbirth (AOR
      2.96, 95% CI 1.60-5.48) and to have had 6 or more previous births, (AOR 1.53, 95%
      CI 1.11-2.12), after adjusting for treatment received. These results suggest
      certain maternal conditions, particularly the presence of another life
      threatening co-morbidity or macerated stillbirth, conferred a higher risk of
      mortality from PPH. This underscores the need for multi-system assessment and a
      comprehensive approach to the treatment of women with pregnancy complications. 

PMID- 23950938
TI  - Increasing adolescent HIV prevalence in Eastern Zimbabwe--evidence of long-term
      survivors of mother-to-child transmission?
AB  - Recent data from the Manicaland HIV/STD Prevention Project, a general-population
      open HIV cohort study, suggested that between 2004 and 2007 HIV prevalence
      amongst males aged 15-17 years in eastern Zimbabwe increased from 1.20% to 2.23%,
      and in females remained unchanged at 2.23% to 2.39%, while prevalence continued
      to decline in the rest of the adult population. We assess whether the more likely
      source of the increase in adolescent HIV prevalence is recent sexual HIV
      acquisition, or the aging of long-term survivors of perinatal HIV acquisition
      that occurred during the early growth of the epidemic. Using data collected
      between August 2006 and November 2008, we investigated associations between
      adolescent HIV and (1) maternal orphanhood and maternal HIV status, (2) reported
      sexual behaviour, and (3) reporting recurring sickness or chronic illness,
      suggesting infected adolescents might be in a late stage of HIV infection. HIV
      infected adolescent males were more likely to be maternal orphans (RR = 2.97,
      p<0.001) and both HIV-infected adolescent males and females were more likely to
      be maternal orphans or have an HIV-infected mother (male RR = 1.83, p<0.001;
      female RR = 16.6, p<0.001). None of 22 HIV-infected adolescent males and only
      three of 23 HIV-infected females reported ever having had sex. HIV-infected
      adolescents were 60% more likely to report illness than HIV-infected young
      adults. Taken together, all three hypotheses suggest that recent increases in
      adolescent HIV prevalence in eastern Zimbabwe are more likely attributable to
      long-term survival of mother-to-child transmission rather than increases in risky
      sexual behaviour. HIV prevalence in adolescents and young adults cannot be used
      as a surrogate for recent HIV incidence, and health systems should prepare for
      increasing numbers of long-term infected adolescents.

PMID- 23950939
TI  - Structural guided scaffold phage display libraries as a source of bio
      therapeutics.
AB  - We have developed a structurally-guided scaffold phage display strategy for
      identification of ligand mimetic bio-therapeutics. As a proof of concept we used
      the ligand of integrin alphavbeta6, a tumour cell surface receptor and a major
      new target for imaging and therapy of many types of solid cancer. NMR structure
      analysis showed that RGD-helix structures are optimal for alphavbeta6 ligand
      interaction, so we designed novel algorithms to generate human single chain
      fragment variable (scFv) libraries with synthetic VH-CDR3 encoding RGD-helix
      hairpins with helices of differing pitch, length and amino acid composition.
      Study of the lead scFv clones D25scFv and D34scFv and their corresponding VH-CDR3
      derived peptides, D25p and D34p, demonstrated: specific binding to recombinant
      and cellular alphavbeta6; inhibition of alphavbeta6-dependent cell and ligand
      adhesion, alphavbeta6-dependent cell internalisation; and selective retention by
      alphavbeta6-expressing, but not alphavbeta6-negative, human xenografts. NMR
      analysis established that both the D25p and D34p retained RGD-helix structures
      confirming the success of the algorithm. In conclusion, scFv libraries can be
      engineered based on ligand structural motifs to increase the likelihood of
      developing powerful bio-therapeutics. 

PMID- 23950940
TI  - Whole cell-SELEX aptamers for highly specific fluorescence molecular imaging of
      carcinomas in vivo.
AB  - BACKGROUND: Carcinomas make up the majority of cancers. Their accurate and
      specific diagnoses are of great significance for the improvement of patients'
      curability. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we report an effectual
      example of the in vivo fluorescence molecular imaging of carcinomas with
      extremely high specificity based on whole cell-SELEX aptamers. Firstly, S6, an
      aptamer against A549 lung carcinoma cells, was adopted and labeled with Cy5 to
      serve as a molecular imaging probe. Flow cytometry assays revealed that Cy5-S6
      could not only specifically label in vitro cultured A549 cells in buffer, but
      also successfully achieve the detection of ex vivo cultured target cells in
      serum. When applied to in vivo imaging, Cy5-S6 was demonstrated to possess high
      specificity in identifying A549 carcinoma through a systematic comparison
      investigation. Particularly, after Cy5-S6 was intravenously injected into nude
      mice which were simultaneously grafted with A549 lung carcinoma and Tca8113
      tongue carcinoma, a much longer retention time of Cy5-S6 in A549 tumor was
      observed and a clear targeted cancer imaging result was presented. On this basis,
      to further promote the application to imaging other carcinomas, LS2 and ZY8,
      which are two aptamers selected by our group against Bel-7404 and SMMC-7721 liver
      carcinoma cells respectively, were tested in a similar way, both in vitro and in
      vivo. Results showed that these aptamers were even effective in differentiating
      liver carcinomas of different subtypes in the same body.
      CONCLUSIONS/SIGNIFICANCE: This work might greatly advance the application of
      whole cell-SELEX aptamers to carcinomas-related in vivo researches.

PMID- 23950941
TI  - Signals from the brainstem sleep/wake centers regulate behavioral timing via the
      circadian clock.
AB  - Sleep-wake cycling is controlled by the complex interplay between two brain
      systems, one which controls vigilance state, regulating the transition between
      sleep and wake, and the other circadian, which communicates time-of-day.
      Together, they align sleep appropriately with energetic need and the day-night
      cycle. Neural circuits connect brain stem sites that regulate vigilance state
      with the suprachiasmatic nucleus (SCN), the master circadian clock, but the
      function of these connections has been unknown. Coupling discrete stimulation of
      pontine nuclei controlling vigilance state with analytical chemical measurements
      of intra-SCN microdialysates in mouse, we found significant neurotransmitter
      release at the SCN and, concomitantly, resetting of behavioral circadian rhythms.
      Depending upon stimulus conditions and time-of-day, SCN acetylcholine and/or
      glutamate levels were augmented and generated shifts of behavioral rhythms. These
      results establish modes of neurochemical communication from brain regions
      controlling vigilance state to the central circadian clock, with behavioral
      consequences. They suggest a basis for dynamic integration across brain systems
      that regulate vigilance states, and a potential vulnerability to altered
      communication in sleep disorders. 

PMID- 23950942
TI  - Population-level impact of same-day microscopy and Xpert MTB/RIF for tuberculosis
      diagnosis in Africa.
AB  - OBJECTIVE: To compare the population-level impact of two World Health
      Organization-endorsed strategies for improving the diagnosis of tuberculosis
      (TB): same-day microscopy and Xpert MTB/RIF (Cepheid, USA). METHODS: We created a
      compartmental transmission model of TB in a representative African community, fit
      to the regional incidence and mortality of TB and HIV. We compared the population
      level reduction in TB burden over ten years achievable with implementation over
      two years of same-day microscopy, Xpert MTB/RIF testing, and the combination of
      both approaches. FINDINGS: Same-day microscopy averted an estimated 11.0% of TB
      incidence over ten years (95% uncertainty range, UR: 3.3%-22.5%), and prevented
      11.8% of all TB deaths (95% UR: 7.7%-27.1%). Scaling up Xpert MTB/RIF to all
      centralized laboratories to achieve 75% population coverage had similar impact on
      incidence (9.3% reduction, 95% UR: 1.9%-21.5%) and greater effect on mortality
      (23.8% reduction, 95% UR: 8.6%-33.4%). Combining the two strategies (i.e., same
      day microscopy plus Xpert MTB/RIF) generated synergistic effects: an 18.7%
      reduction in incidence (95% UR: 5.6%-39.2%) and 33.1% reduction in TB mortality
      (95% UR: 18.1%-50.2%). By the end of year ten, combining same-day microscopy and
      Xpert MTB/RIF could reduce annual TB mortality by 44% relative to the current
      standard of care. CONCLUSION: Scaling up novel diagnostic tests for TB and
      optimizing existing ones are complementary strategies that, when combined, may
      have substantial impact on TB epidemics in Africa.

PMID- 23950943
TI  - Validating RNAi phenotypes in Drosophila using a synthetic RNAi-resistant
      transgene.
AB  - RNA interference (RNAi) is a powerful and widely used approach to investigate
      gene function, but a major limitation of the approach is the high incidence of
      non-specific phenotypes that arise due to off-target effects. We previously
      showed that RNAi-mediated knock-down of pico, which encodes the only member of
      the MRL family of adapter proteins in Drosophila, resulted in reduction in cell
      number and size leading to reduced tissue growth. In contrast, a recent study
      reported that pico knockdown leads to tissue dysmorphology, pointing to an
      indirect role for pico in the control of wing size. To understand the cause of
      this disparity we have utilised a synthetic RNAi-resistant transgene, which bears
      minimal sequence homology to the predicted dsRNA but encodes wild type Pico
      protein, to reanalyse the RNAi lines used in the two studies. We find that the
      RNAi lines from different sources exhibit different effects, with one set of
      lines uniquely resulting in a tissue dysmorphology phenotype when expressed in
      the developing wing. Importantly, the loss of tissue morphology fails to be
      complemented by co-overexpression of RNAi-resistant pico suggesting that this
      phenotype is the result of an off-target effect. This highlights the importance
      of careful validation of RNAi-induced phenotypes, and shows the potential of
      synthetic transgenes for their experimental validation. 

PMID- 23950944
TI  - p53 cooperates with Sp1 to regulate breed-dependent expression of glucocorticoid
      receptor in the liver of preweaning piglets.
AB  - Previous studies indicate that Chinese indigenous pig breeds demonstrate distinct
      pattern of glucocorticoid receptor (GR) expression, which is associated with
      their unique growth and metabolic phenotypes. Here we sought to unravel the
      transcriptional mechanisms underlying the breed-specific hepatic GR expression in
      preweaning Chinese Erhualian (EHL) and Western Large White (LW) piglets. Total GR
      mRNA and the predominant GR mRNA variant 1-9/10 were expressed significantly
      higher in EHL compared with LW piglets (P<0.01), which was associated with more
      enriched histone H3 acetylation on 1-9/10 promoter (P<0.05). Nuclear content of
      transcription factor specificity protein 1 (Sp1) was significantly lower in EHL
      piglets, yet its binding to GR 1-9/10 promoter was significantly higher in EHL
      piglets, as revealed by chromatin immunoprecipitation assays. Although p53
      binding to GR promoter 1-9/10 did not differ between breeds, expression of p53
      mRNA and protein, as well as its binding to Sp1, were significantly higher in EHL
      piglets. Moreover, p53 activator doxorubicin significantly enhanced GR 1-9/10
      promoter activity in HepG2 cells at 100 nM, which was associated with
      significantly higher protein content of p53 and GR. Sp1 inhibitor, mithramycin A,
      significantly inhibited (P<0.05) the basal activity of GR promoter 1-9/10 and
      completely blocked doxorubicin -induced activation of GR promoter 1-9/10. These
      data indicate that higher hepatic GR expression in EHL piglets attributes mainly
      to the enhanced transcription of GR promoter 1-9/10, which is achieved from breed
      specific interaction of p53 and Sp1 on porcine GR 1-9/10 promoter. 

PMID- 23950945
TI  - Extracting labeled topological patterns from samples of networks.
AB  - An advanced graph theoretical approach is introduced that enables a higher level
      of functional interpretation of samples of directed networks with identical fixed
      pairwise different vertex labels that are drawn from a particular population.
      Compared to the analysis of single networks, their investigation promises to
      yield more detailed information about the represented system. Often patterns of
      directed edges in sample element networks are too intractable for a direct
      evaluation and interpretation. The new approach addresses the problem of
      simplifying topological information and characterizes such a sample of networks
      by finding its locatable characteristic topological patterns. These patterns,
      essentially sample-specific network motifs with vertex labeling, might represent
      the essence of the intricate topological information contained in all sample
      element networks and provides as well a means of differentiating network samples.
      Central to the accurateness of this approach is the null model and its
      properties, which is needed to assign significance to topological patterns. As a
      proof of principle the proposed approach has been applied to the analysis of
      networks that represent brain connectivity before and during painful stimulation
      in patients with major depression and in healthy subjects. The accomplished
      reduction of topological information enables a cautious functional interpretation
      of the altered neuronal processing of pain in both groups. 

PMID- 23950946
TI  - A novel method for rapid hybridization of DNA to a solid support.
AB  - Here we present a novel approach entitled Magnetic Forced Hybridization (MFH)
      that provides the means for efficient and direct hybridization of target nucleic
      acids to complementary probes immobilized on a glass surface in less than 15
      seconds at ambient temperature. In addition, detection is carried out instantly
      since the beads become visible on the surface. The concept of MFH was tested for
      quality control of array manufacturing, and was combined with a multiplex
      competitive hybridization (MUCH) approach for typing of Human Papilloma Virus
      (HPV). Magnetic Forced Hybridization of bead-DNA constructs to a surface achieves
      a significant reduction in diagnostic testing time. In addition, readout of
      results by visual inspection of the unassisted eye eliminates the need for
      additional expensive instrumentation. The method uses the same set of beads
      throughout the whole process of manipulating and washing DNA constructs prior to
      detection, as in the actual detection step itself. 

PMID- 23950947
TI  - Varietal tracing of virgin olive oils based on plastid DNA variation profiling.
AB  - Olive oil traceability remains a challenge nowadays. DNA analysis is the
      preferred approach to an effective varietal identification, without any
      environmental influence. Specifically, olive organelle genomics is the most
      promising approach for setting up a suitable set of markers as they would not
      interfere with the pollinator variety DNA traces. Unfortunately, plastid DNA
      (cpDNA) variation of the cultivated olive has been reported to be low. This
      feature could be a limitation for the use of cpDNA polymorphisms in forensic
      analyses or oil traceability, but rare cpDNA haplotypes may be useful as they can
      help to efficiently discriminate some varieties. Recently, the sequencing of
      olive plastid genomes has allowed the generation of novel markers. In this study,
      the performance of cpDNA markers on olive oil matrices, and their applicability
      on commercial Protected Designation of Origin (PDO) oils were assessed. By using
      a combination of nine plastid loci (including multi-state microsatellites and
      short indels), it is possible to fingerprint six haplotypes (in 17 Spanish olive
      varieties), which can discriminate high-value commercialized cultivars with PDO.
      In particular, a rare haplotype was detected in genotypes used to produce a
      regional high-value commercial oil. We conclude that plastid haplotypes can help
      oil traceability in commercial PDO oils and set up an experimental methodology
      suitable for organelle polymorphism detection in the complex olive oil matrices. 

PMID- 23950948
TI  - miR-105 inhibits prostate tumour growth by suppressing CDK6 levels.
AB  - A significant role for micro (mi)RNA in the regulation of gene expression in
      tumours has been recently established. In order to further understand how miRNA
      expression may contribute to prostate tumour growth and progression, we evaluated
      expression of miRNA in two invasive prostate tumour lines, PC3 and DU145, and
      compared it to that in normal prostate epithelial cells. Although a number of
      miRNAs were differentially expressed, we focused our analysis on miR-105, a novel
      miRNA not previously linked to prostate cancer. miR-105 levels were significantly
      decreased in both tumour cell lines in comparison to normal prostate epithelial
      cells. To determine its potential role in prostate cancer pathogenesis, we
      overexpressed miR-105 in both PC3 and DU145 cells and determined its effect on
      various tumourigenic properties. miR-105 overexpression inhibited tumour cell
      proliferation, tumour growth in anchorage-independent three-dimensional
      conditions and tumour invasion in vitro, properties of highly aggressive tumour
      cells. Of potential clinical significance, miR-105 overexpression inhibited
      tumour growth in vivo in xenograft models using these cell lines. We further
      identified CDK6 as a putative target of miR-105 which is likely a main
      contributor to the inhibition of tumour cell growth observed in our assays. Our
      results suggest that miR-105 inhibits tumour cell proliferation and hence may
      represent a novel therapeutically relevant cellular target to inhibit tumour
      growth or a marker of aggressive tumours in prostate cancer patients. 

PMID- 23950949
TI  - A comparative analysis of industrial Escherichia coli K-12 and B strains in high
      glucose batch cultivations on process-, transcriptome- and proteome level.
AB  - Escherichia coli K-12 and B strains are among the most frequently used bacterial
      hosts for production of recombinant proteins on an industrial scale. To improve
      existing processes and to accelerate bioprocess development, we performed a
      detailed host analysis. We investigated the different behaviors of the E. coli
      production strains BL21, RV308, and HMS174 in response to high-glucose
      concentrations. Tightly controlled cultivations were conducted under defined
      environmental conditions for the in-depth analysis of physiological behavior. In
      addition to acquisition of standard process parameters, we also used DNA
      microarray analysis and differential gel electrophoresis (Ettan(TM) DIGE). Batch
      cultivations showed different yields of the distinct strains for cell dry mass
      and growth rate, which were highest for BL21. In addition, production of acetate,
      triggered by excess glucose supply, was much higher for the K-12 strains compared
      to the B strain. Analysis of transcriptome data showed significant alteration in
      347 of 3882 genes common among all three hosts. These differentially expressed
      genes included, for example, those involved in transport, iron acquisition, and
      motility. The investigation of proteome patterns additionally revealed a high
      number of differentially expressed proteins among the investigated hosts. The
      subsequently selected 38 spots included proteins involved in transport and
      motility. The results of this comprehensive analysis delivered a full genomic
      picture of the three investigated strains. Differentially expressed groups for
      targeted host modification were identified like glucose transport or iron
      acquisition, enabling potential optimization of strains to improve yield and
      process quality. Dissimilar growth profiles of the strains confirm different
      genotypes. Furthermore, distinct transcriptome patterns support differential
      regulation at the genome level. The identified proteins showed high agreement
      with the transcriptome data and suggest similar regulation within a host at both
      levels for the identified groups. Such host attributes need to be considered in
      future process design and operation. 

PMID- 23950950
TI  - Prolonged mechanical ventilation alters the expression pattern of angio
      neogenetic factors in a pre-clinical rat model.
AB  - OBJECTIVE: Mechanical ventilation (MV) is a life saving intervention for patients
      with respiratory failure. Even after 6 hours of MV, diaphragm atrophy and
      dysfunction (collectively referred to as ventilator-induced diaphragmatic
      dysfunction, VIDD) occurs in concert with a blunted blood flow and oxygen
      delivery. The regulation of hypoxia sensitive factors (i.e. hypoxia inducible
      factor 1alpha, 2alpha (HIF-1alpha,-2alpha), vascular endothelial growth factor
      (VEGF)) and angio-neogenetic factors (angiopoietin 1-3, Ang) might contribute to
      reactive and compensatory alterations in diaphragm muscle. METHODS: Male Wistar
      rats (n = 8) were ventilated for 24 hours or directly sacrificed (n = 8),
      diaphragm and mixed gastrocnemius muscle tissue was removed. Quantitative real
      time PCR and western blot analyses were performed to detect changes in angio
      neogenetic factors and inflammatory markers. Tissues were stained using Isolectin
      (IB 4) to determine capillarity and calculate the capillary/fiber ratio. RESULTS:
      MV resulted in up-regulation of Ang 2 and HIF-1alpha mRNA in both diaphragm and
      gastrocnemius, while VEGF mRNA was down-regulated in both tissues. HIF-2alpha
      mRNA was reduced in both tissues, while GLUT 4 mRNA was increased in
      gastrocnemius and reduced in diaphragm samples. Protein levels of VEGF, HIF
      1alpha, -2alpha and 4 did not change significantly. Additionally, inflammatory
      cytokine mRNA (Interleukin (IL)-6, IL-1beta and TNF alpha) were elevated in
      diaphragm tissue. CONCLUSION: The results demonstrate that 24 hrs of MV and the
      associated limb disuse induce an up-regulation of angio-neogenetic factors that
      are connected to HIF-1alpha. Changes in HIF-1alpha expression may be due to
      several interactions occurring during MV.

PMID- 23950952
TI  - Evidence for the circulation of equine encephalosis virus in Israel since 2001.
AB  - Equine encephalosis virus (EEV) distribution was thought to be limited to
      southern Africa until 2008 when we reported EEV in Israel. It was then assumed
      that the clinical presentation resembled the initial incursion in Israel. To
      investigate further we conducted a retrospective analysis of equine sera, which
      had been collected for diagnosis of other suspected diseases, via serum
      neutralisation test. The data demonstrated that EEV was circulating as early as
      2001 with incidence ranging from 20-100% for time period 2001-2008. As the
      symptoms of EEV can be similar to other equine notifiable diseases this is a
      significant finding which highlights the need for vigilance and education to
      accurately diagnose new and emerging diseases. 

PMID- 23950951
TI  - EndocineTM, N3OA and N3OASq; three mucosal adjuvants that enhance the immune
      response to nasal influenza vaccination.
AB  - Annual outbreaks of seasonal influenza are controlled or prevented through
      vaccination in many countries. The seasonal vaccines used are either inactivated,
      currently administered parenterally, or live-attenuated given intranasally. In
      this study three mucosal adjuvants were examined for the influence on the humoral
      (mucosal and systemic) and cellular influenza A-specific immune responses induced
      by a nasally administered vaccine. We investigated in detail how the anionic
      EndocineTM and the cationic adjuvants N3OA and N3OASq mixed with a split
      inactivated influenza vaccine induced influenza A-specific immune responses as
      compared to the vaccine alone after intranasal immunization. The study showed
      that nasal administration of a split virus vaccine together with EndocineTM or
      N3OA induced significantly higher humoral and cell-mediated immune responses than
      the non-adjuvanted vaccine. N3OASq only significantly increased the cell-mediated
      immune response. Furthermore, nasal administration of the influenza vaccine in
      combination with any of the adjuvants; EndocineTM, N3OA or N3OASq, significantly
      enhanced the mucosal immunity against influenza HA protein. Thus the addition of
      these mucosal adjuvants leads to enhanced immunity in the most relevant tissues,
      the upper respiratory tract and the systemic circulation. Nasal influenza
      vaccination with an inactivated split vaccine can therefore provide an important
      mucosal immune response, which is often low or absent after traditional
      parenteral vaccination. 

PMID- 23950953
TI  - Electronegative low-density lipoprotein increases C-reactive protein expression
      in vascular endothelial cells through the LOX-1 receptor.
AB  - OBJECTIVES: Increased plasma C-reactive protein (CRP) levels are associated with
      the occurrence and severity of acute coronary syndrome. We investigated whether
      CRP can be generated in vascular endothelial cells (ECs) after exposure to the
      most electronegative subfraction of low-density lipoprotein (LDL), L5, which is
      atherogenic to ECs. Because L5 and CRP are both ligands for the lectin-like
      oxidized LDL receptor-1 (LOX-1), we also examined the role of LOX-1. METHODS AND
      RESULTS: Plasma LDL samples isolated from asymptomatic hypercholesterolemic (LDL
      cholesterol [LDL-C] levels, 154.6+/-20 mg/dL; n = 7) patients and
      normocholesterolemic (LDL-C levels, 86.1+/-21 mg/dL; P<0.001; n = 7) control
      individuals were chromatographically resolved into 5 subfractions, L1-L5. The L5
      percentage (L5%) and the plasma L5 concentration ([L5]  =  L5% * LDL-C) in the
      patient and control groups were 8.1+/-2% vs. 2.3+/-1% (P<0.001) and 12.6+/-4
      mg/dL vs. 1.9+/-1 mg/dL (P<0.001), respectively. In hypercholesterolemic patients
      treated with atorvastatin for 6 months (10 mg/day), [L5] decreased from 12.6+/-4
      mg/dL to 4.5+/-1.1 mg/dL (P = 0.011; n = 5), whereas both [L5] and L5% returned
      to baseline levels in 2 noncompliant patients 3 months after discontinuation. In
      cultured human aortic ECs (HAECs), L5 upregulated CRP expression in a dose- and
      time-dependent manner up to 2.5-fold (P<0.01), whereas the least electronegative
      subfraction, L1, had no effect. DiI-labeled L1, internalized through the LDL
      receptor, became visible inside HAECs within 30 seconds. In contrast, DiI-labeled
      L5, internalized through LOX-1, became apparent after 5 minutes. L5-induced CRP
      expression manifested at 30 minutes and was attenuated by neutralizing LOX-1.
      After 30 minutes, L5 but not L1 induced reactive oxygen species (ROS) production.
      Both L5-induced ROS and CRP production were attenuated by ROS inhibitor N-acetyl
      cysteine. CONCLUSIONS: Our results suggest that CRP, L5, and LOX-1 form a cyclic
      mechanism in atherogenesis and that reducing plasma L5 levels with atorvastatin
      disrupts the vascular toxicity of L5.

PMID- 23950954
TI  - Adherence to the WHO's healthy diet indicator and overall cancer risk in the EPIC
      NL cohort.
AB  - BACKGROUND: A healthy dietary pattern defined by international recommendations of
      the World Health Organisation (WHO) has been shown to reduce overall mortality
      risk. It is unknown whether this healthy dietary pattern is associated with
      overall cancer incidence. DESIGN: In total 35,355 men and women within the Dutch
      European Prospective Investigation into Cancer and Nutrition-cohort were followed
      for cancer occurrence. Diet was assessed through a validated food-frequency
      questionnaire. We computed a dietary score for all participants based on the
      seven WHO dietary guidelines for the prevention of chronic diseases (Healthy Diet
      Indicator (HDI)). We used the existing HDI score based on the 1990 WHO
      guidelines, and adapted it to meet with the 2002 WHO guidelines. Multivariate
      adjusted Cox proportional hazards analysis was used to examine the association
      between adherence to the HDI and subsequent overall cancer risk. RESULTS: A
      number of 3,007 new cancers were identified during a mean follow-up of 12.7
      years. Adherence to the HDI was not associated with a reduced overall cancer
      risk. The hazard ratio (HR) of overall cancer associated with a one-point
      increment of the HDI was 0.96 (95% CI 0.89-1.03) in men, and 1.00 (95% CI 0.96
      1.04) in women. Adherence to the HDI was not associated with smoking-related
      cancer ((HR men: 0.94 (95% CI 0.84-1.04); HR women: 1.00 (95% CI 0.94-1.07)), or
      alcohol-related cancer ((HR men: 1.02 (95% CI 0.87-1.20); HR women: 1.03 (95% CI
      0.98-1.08)). CONCLUSIONS: Greater adherence to the WHO's Healthy Diet Indicator,
      a dietary pattern for prevention of chronic diseases, was not associated with
      reduced overall, smoking-related or alcohol-related cancer risk in men or women.

PMID- 23950955
TI  - Characterization of Staphylococcus and Corynebacterium clusters in the human
      axillary region.
AB  - The skin microbial community is regarded as essential for human health and well
      being, but likewise plays an important role in the formation of body odor in, for
      instance, the axillae. Few molecular-based research was done on the axillary
      microbiome. This study typified the axillary microbiome of a group of 53 healthy
      subjects. A profound view was obtained of the interpersonal, intrapersonal and
      temporal diversity of the human axillary microbiota. Denaturing gradient gel
      electrophoresis (DGGE) and next generation sequencing on 16S rRNA gene region
      were combined and used as extent to each other. Two important clusters were
      characterized, where Staphylococcus and Corynebacterium species were the abundant
      species. Females predominantly clustered within the Staphylococcus cluster (87%,
      n = 17), whereas males clustered more in the Corynebacterium cluster (39%, n =
      36). The axillary microbiota was unique to each individual. Left-right asymmetry
      occurred in about half of the human population. For the first time, an elaborate
      study was performed on the dynamics of the axillary microbiome. A relatively
      stable axillary microbiome was noticed, although a few subjects evolved towards
      another stable community. The deodorant usage had a proportional linear influence
      on the species diversity of the axillary microbiome. 

PMID- 23950956
TI  - Deep-sea benthic footprint of the deepwater horizon blowout.
AB  - The Deepwater Horizon (DWH) accident in the northern Gulf of Mexico occurred on
      April 20, 2010 at a water depth of 1525 meters, and a deep-sea plume was detected
      within one month. Oil contacted and persisted in parts of the bottom of the deep
      sea in the Gulf of Mexico. As part of the response to the accident, monitoring
      cruises were deployed in fall 2010 to measure potential impacts on the two main
      soft-bottom benthic invertebrate groups: macrofauna and meiofauna. Sediment was
      collected using a multicorer so that samples for chemical, physical and
      biological analyses could be taken simultaneously and analyzed using multivariate
      methods. The footprint of the oil spill was identified by creating a new variable
      with principal components analysis where the first factor was indicative of the
      oil spill impacts and this new variable mapped in a geographic information system
      to identify the area of the oil spill footprint. The most severe relative
      reduction of faunal abundance and diversity extended to 3 km from the wellhead in
      all directions covering an area about 24 km(2). Moderate impacts were observed up
      to 17 km towards the southwest and 8.5 km towards the northeast of the wellhead,
      covering an area 148 km(2). Benthic effects were correlated to total petroleum
      hydrocarbon, polycyclic aromatic hydrocarbons and barium concentrations, and
      distance to the wellhead; but not distance to hydrocarbon seeps. Thus, benthic
      effects are more likely due to the oil spill, and not natural hydrocarbon
      seepage. Recovery rates in the deep sea are likely to be slow, on the order of
      decades or longer. 

PMID- 23950957
TI  - Factor structure and longitudinal measurement invariance of the demand control
      support model: an evidence from the Swedish Longitudinal Occupational Survey of
      Health (SLOSH).
AB  - OBJECTIVES: To examine the factor structure and to evaluate the longitudinal
      measurement invariance of the demand-control-support questionnaire (DCSQ), using
      the Swedish Longitudinal Occupational Survey of Health (SLOSH). METHODS: A
      confirmatory factor analysis (CFA) and multi-group confirmatory factor analysis
      (MGCFA) models within the framework of structural equation modeling (SEM) have
      been used to examine the factor structure and invariance across time. RESULTS:
      Four factors: psychological demand, skill discretion, decision authority and
      social support, were confirmed by CFA at baseline, with the best fit obtained by
      removing the item repetitive work of skill discretion. A measurement error
      correlation (0.42) between work fast and work intensively for psychological
      demands was also detected. Acceptable composite reliability measures were
      obtained except for skill discretion (0.68). The invariance of the same factor
      structure was established, but caution in comparing mean levels of factors over
      time is warranted as lack of intercept invariance was evident. However, partial
      intercept invariance was established for work intensively. CONCLUSION: Our
      findings indicate that skill discretion and decision authority represent two
      distinct constructs in the retained model. However removing the item repetitive
      work along with either work fast or work intensively would improve model fit.
      Care should also be taken while making comparisons in the constructs across time.
      Further research should investigate invariance across occupations or socio
      economic classes.

PMID- 23950958
TI  - Novel VEGF decoy receptor fusion protein conbercept targeting multiple VEGF
      isoforms provide remarkable anti-angiogenesis effect in vivo.
AB  - VEGF family factors are known to be the principal stimulators of abnormal
      angiogenesis, which play a fundamental role in tumor and various ocular diseases.
      Inhibition of VEGF is widely applied in antiangiogenic therapy. Conbercept is a
      novel decoy receptor protein constructed by fusing VEGF receptor 1 and VEGF
      receptor 2 extracellular domains with the Fc region of human immunoglobulin. In
      this study, we systematically evaluated the binding affinity of conbercept with
      VEGF isoforms and PlGF by using anti-VEGF antibody (Avastin) as reference.
      BIACORE and ELISA assay results indicated that conbercept could bind different
      VEGF-A isoforms with higher affinity than reference. Furthermore, conbercept
      could also bind VEGF-B and PlGF, whereas Avastin showed no binding. Oxygen
      induced retinopathy model showed that conbercept could inhibit the formation of
      neovasularizations. In tumor-bearing nude mice, conbercept could also suppress
      tumor growth very effectively in vivo. Overall, our study have demonstrated that
      conbercept could bind with high affinity to multiple VEGF isoforms and
      consequently provide remarkable anti-angiogenic effect, suggesting the
      possibility to treat angiogenesis-related diseases such as cancer and wet AMD
      etc. 

PMID- 23950959
TI  - Analysis of the dominant effects mediated by wild type or R120G mutant of alphaB
      crystallin (HspB5) towards Hsp27 (HspB1).
AB  - Several human small heat shock proteins (sHsps) are phosphorylated oligomeric
      chaperones that enhance stress resistance. They are characterized by their
      ability to interact and form polydispersed hetero-oligomeric complexes. We have
      analyzed the cellular consequences of the stable expression of either wild type
      HspB5 or its cataracts and myopathies inducing R120G mutant in growing and
      oxidative stress treated HeLa cells that originally express only HspB1. Here, we
      describe that wild type and mutant HspB5 induce drastic and opposite effects on
      cell morphology and oxidative stress resistance. The cellular distribution and
      phosphorylation of these polypeptides as well as the oligomerization profile of
      the resulting hetero-oligomeric complexes formed by HspB1 with the two types of
      exogenous polypeptides revealed the dominant effects induced by HspB5
      polypeptides towards HspB1. The R120G mutation enhanced the native size and salt
      resistance of HspB1-HspB5 complex. However, in oxidative conditions the
      interaction between HspB1 and mutant HspB5 was drastically modified resulting in
      the aggregation of both partners. The mutation also induced the redistribution of
      HspB1 phosphorylated at serine 15, originally observed at the level of the small
      oligomers that do not interact with wild type HspB5, to the large oligomeric
      complex formed with mutant HspB5. This phosphorylation stabilized the interaction
      of HspB1 with mutant HspB5. A dominant negative effect towards HspB1 appears
      therefore as an important event in the cellular sensitivity to oxidative stress
      mediated by mutated HspB5 expression. These observations provide novel data that
      describe how a mutated sHsp can alter the protective activity of another member
      of this family of chaperones. 

PMID- 23950960
TI  - Species-specific and cross-reactive IgG1 antibody binding to viral capsid protein
      1 (VP1) antigens of human rhinovirus species A, B and C.
AB  - BACKGROUND: Human rhinoviruses (HRV) are associated with upper and lower
      respiratory illnesses, including severe infections causing hospitalization in
      both children and adults. Although the clinical significance of HRV infections is
      now well established, no detailed investigation of the immune response against
      HRV has been performed. The purpose of this study was to assess the IgG1 antibody
      response to the three known HRV species, HRV-A, -B and -C in healthy subjects.
      METHODS: Recombinant polypeptides of viral capsid protein 1 (VP1) from two
      genotypes of HRV-A, -B and -C were expressed as glutathione S-transferase (GST)
      fusion proteins and purified by affinity and then size exclusion chromatography.
      The presence of secondary structures similar to the natural antigens was verified
      by circular dichroism analysis. Total and species-specific IgG1 measurements were
      quantitated by immunoassays and immunoabsorption using sera from 63 healthy
      adults. RESULTS: Most adult sera reacted with the HRV VP1 antigens, at high
      titres. As expected, strong cross-reactivity between HRV genotypes of the same
      species was found. A high degree of cross-reactivity between different HRV
      species was also evident, particularly between HRV-A and HRV-C. Immunoabsorption
      studies revealed HRV-C specific titres were markedly and significantly lower than
      the HRV-A and HRV-B specific titres (P<0.0001). A truncated construct of HRV-C
      VP1 showed greater specificity in detecting anti-HRV-C antibodies. CONCLUSIONS:
      High titres of IgG1 antibody were bound by the VP1 capsid proteins of HRV-A, -B
      and -C, but for the majority of people, a large proportion of the antibody to HRV
      C was cross-reactive, especially to HRV-A. The improved specificity found for the
      truncated HRV-C VP1 indicates species-specific and cross-reactive regions could
      be defined.

PMID- 23950961
TI  - Electrophysiological heterogeneity of fast-spiking interneurons: chandelier
      versus basket cells.
AB  - In the prefrontal cortex, parvalbumin-positive inhibitory neurons play a
      prominent role in the neural circuitry that subserves working memory, and
      alterations in these neurons contribute to the pathophysiology of schizophrenia.
      Two morphologically distinct classes of parvalbumin neurons that target the
      perisomatic region of pyramidal neurons, chandelier cells (ChCs) and basket cells
      (BCs), are generally thought to have the same "fast-spiking" phenotype, which is
      characterized by a short action potential and high frequency firing without
      adaptation. However, findings from studies in different species suggest that
      certain electrophysiological membrane properties might differ between these two
      cell classes. In this study, we assessed the physiological heterogeneity of fast
      spiking interneurons as a function of two factors: species (macaque monkey vs.
      rat) and morphology (chandelier vs. basket). We showed previously that
      electrophysiological membrane properties of BCs differ between these two species.
      Here, for the first time, we report differences in ChCs membrane properties
      between monkey and rat. We also found that a number of membrane properties
      differentiate ChCs from BCs. Some of these differences were species-independent
      (e.g., fast and medium afterhyperpolarization, firing frequency, and depolarizing
      sag), whereas the differences in the first spike latency between ChCs and BCs
      were species-specific. Our findings indicate that different combinations of
      electrophysiological membrane properties distinguish ChCs from BCs in rodents and
      primates. Such electrophysiological differences between ChCs and BCs likely
      contribute to their distinctive roles in cortical circuitry in each species. 

PMID- 23950962
TI  - Identification and characterization of a novel aac(6')-Iag associated with the
      blaIMP-1-integron in a multidrug-resistant Pseudomonas aeruginosa.
AB  - In a continuing study from Dec 2006 to Apr 2008, we characterized nine multi-drug
      resistant Pseudomonas aeruginosa strains isolated from four patients in a ward at
      the Hiroshima University Hospital, Japan. Pulsed-field gel electrophoresis of
      SpeI-digested genomic DNAs from the isolates suggested the clonal expansion of a
      single strain; however, only one strain, NK0009, was found to produce metallo
      beta-lactamase. PCR and subsequent sequencing analysis indicated NK0009 possessed
      a novel class 1 integron, designated as In124, that carries an array of four gene
      cassettes: a novel aminoglycoside (AG) resistance gene, aac(6')-Iag, blaIMP-1, a
      truncated form of blaIMP-1, and a truncated form of aac(6')-Iag. The aac(6')-Iag
      encoded a 167-amino-acid protein that shows 40% identity with AAC(6')-Iz.
      Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase
      activity using thin-layer chromatography (TLC) and MS spectrometric analysis.
      Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin,
      dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to
      gentamicin. A conjugation experiment and subsequent Southern hybridization with
      the gene probes for blaIMP-1 and aac(6')-Ig strongly suggested In124 is on a
      conjugal plasmid. Transconjugants acquired resistance to gentamicin and were
      resistant to virtually all AGs, suggesting that the In124 conjugal plasmid also
      possesses a gene conferring resistance to gentamicin.

PMID- 23950963
TI  - Injury related risk behaviour: a Health belief model-based study of primary
      school students in a safe community in Shanghai.
AB  - AIM: To explore the relationship between Health belief model (HBM) and children
      and adolescents' unintentional injury risk behavior, to add some useful
      information for injury prevention. METHODOLOGY: We investigated injury related
      health risk behavior and health belief status of students at primary schools
      grade 3 to 4, in a Safe Community, in Shanghai. Self-administered injury
      questionnaires were used to investigate risk behavior of students and HBM
      factors. PRINCIPAL FINDINGS: The prevalence of risk behavior among students
      reported in this community was high. HBM scores showed differences between two
      groups of students classified by whether they had risk behavior or not. Self
      efficacy was highly related with the status of socio-psychological behavior.
      SIGNIFICANCE: HBM has been widely used in explaining the disease-related
      behavior; however, it has been seldom used in injury-related behavior. The study
      demonstrated important relation of HBM to students' injury issues, and HBM could
      explain injury related behavior as well, especially for traffic injury-related
      behavior. When developing injury prevention strategies, we can take it into
      account.

PMID- 23950964
TI  - Combining evidence of preferential gene-tissue relationships from multiple
      sources.
AB  - An important challenge in drug discovery and disease prognosis is to predict
      genes that are preferentially expressed in one or a few tissues, i.e. showing a
      considerably higher expression in one tissue(s) compared to the others. Although
      several data sources and methods have been published explicitly for this purpose,
      they often disagree and it is not evident how to retrieve these genes and how to
      distinguish true biological findings from those that are due to choice-of-method
      and/or experimental settings. In this work we have developed a computational
      approach that combines results from multiple methods and datasets with the aim to
      eliminate method/study-specific biases and to improve the predictability of
      preferentially expressed human genes. A rule-based score is used to merge and
      assign support to the results. Five sets of genes with known tissue specificity
      were used for parameter pruning and cross-validation. In total we identify 3434
      tissue-specific genes. We compare the genes of highest scores with the public
      databases: PaGenBase (microarray), TiGER (EST) and HPA (protein expression data).
      The results have 85% overlap to PaGenBase, 71% to TiGER and only 28% to HPA. 99%
      of our predictions have support from at least one of these databases. Our
      approach also performs better than any of the databases on identifying drug
      targets and biomarkers with known tissue-specificity. 

PMID- 23950965
TI  - Recovery from posttraumatic stress symptoms: a qualitative study of attributions
      in survivors of war.
AB  - OBJECTIVE: The study explored factors to which people traumatized by war
      attribute their recovery from posttraumatic symptoms and from war experiences.
      METHODS: In-depth interviews were conducted with two groups of participants with
      mental sequelae of the war in the former Yugoslavia: 26 people who had recovered
      from posttraumatic stress disorder (PTSD) and 17 people with ongoing symptoms of
      PTSD. Participants could attribute their recovery to any event, person or process
      in their life. The material was subjected to thematic analysis. RESULTS: Eight
      themes covered all factors to which participants attributed their recovery. Six
      themes described healing factors relevant for both groups of participants: social
      attachment and support, various strategies of coping with symptoms, personality
      hardiness, mental health treatment, received material support, and normalization
      of everyday life. In addition to the common factors, recovered participants
      reported community involvement as healing, and recovered refugees identified also
      feeling safe after resolving their civil status as helpful. Unique to the
      recovered group was that they maintained reciprocal relations in social
      attachment and support, employed future-oriented coping and emphasised their
      resilient personality style. CONCLUSIONS: The reported factors of recovery are
      largely consistent with models of mental health protection, models of resilience
      and recommended interventions in the aftermath of massive trauma. Yet, they add
      the importance of a strong orientation towards the future, a reciprocity in
      receiving and giving social support and involvement in meaningful activities that
      ensure social recognition as a productive and valued individual. The findings can
      inform psychosocial interventions to facilitate recovery from posttraumatic
      symptoms of people affected by war and upheaval.

PMID- 23950966
TI  - Alternative splice variants in TIM barrel proteins from human genome correlate
      with the structural and evolutionary modularity of this versatile protein fold.
AB  - After the surprisingly low number of genes identified in the human genome,
      alternative splicing emerged as a major mechanism to generate protein diversity
      in higher eukaryotes. However, it is still not known if its prevalence along the
      genome evolution has contributed to the overall functional protein diversity or
      if it simply reflects splicing noise. The (betaalpha)8 barrel or TIM barrel is
      one of the most frequent, versatile, and ancient fold encountered among enzymes.
      Here, we analyze the structural modifications present in TIM barrel proteins from
      the human genome product of alternative splicing events. We found that 87% of all
      splicing events involved deletions; most of these events resulted in protein
      fragments that corresponded to the (betaalpha)2, (betaalpha)4, (betaalpha)5,
      (betaalpha)6, and (betaalpha)7 subdomains of TIM barrels. Because approximately
      7% of all the splicing events involved internal beta-strand substitutions, we
      decided, based on the genomic data, to design beta-strand and alpha-helix
      substitutions in a well-studied TIM barrel enzyme. The biochemical
      characterization of one of the chimeric variants suggests that some of the splice
      variants in the human genome with beta-strand substitutions may be evolving novel
      functions via either the oligomeric state or substrate specificity. We provide
      results of how the splice variants represent subdomains that correlate with the
      independently folding and evolving structural units previously reported. This
      work is the first to observe a link between the structural features of the barrel
      and a recurrent genetic mechanism. Our results suggest that it is reasonable to
      expect that a sizeable fraction of splice variants found in the human genome
      represent structurally viable functional proteins. Our data provide additional
      support for the hypothesis of the origin of the TIM barrel fold through the
      assembly of smaller subdomains. We suggest a model of how nature explores new
      proteins through alternative splicing as a mechanism to diversify the proteins
      encoded in the human genome. 

PMID- 23950967
TI  - Cost-effectiveness of a community pharmacist intervention in patients with
      depression: a randomized controlled trial (PRODEFAR Study).
AB  - BACKGROUND: Non-adherence to antidepressants generates higher costs for the
      treatment of depression. Little is known about the cost-effectiveness of
      pharmacist's interventions aimed at improving adherence to antidepressants. The
      study aimed to evaluate the cost-effectiveness of a community pharmacist
      intervention in comparison with usual care in depressed patients initiating
      treatment with antidepressants in primary care. METHODS: Patients were recruited
      by general practitioners and randomized to community pharmacist intervention (87)
      that received an educational intervention and usual care (92). Adherence to
      antidepressants, clinical symptoms, Quality-Adjusted Life-Years (QALYs), use of
      healthcare services and productivity losses were measured at baseline, 3 and 6
      months. RESULTS: There were no significant differences between groups in costs or
      effects. From a societal perspective, the incremental cost-effectiveness ratio
      (ICER) for the community pharmacist intervention compared with usual care was
      ?1,866 for extra adherent patient and ?9,872 per extra QALY. In terms of
      remission of depressive symptoms, the usual care dominated the community
      pharmacist intervention. If willingness to pay (WTP) is ?30,000 per extra
      adherent patient, remission of symptoms or QALYs, the probability of the
      community pharmacist intervention being cost-effective was 0.71, 0.46 and 0.75,
      respectively (societal perspective). From a healthcare perspective, the
      probability of the community pharmacist intervention being cost-effective in
      terms of adherence, QALYs and remission was of 0.71, 0.76 and 0.46, respectively,
      if WTP is ?30,000. CONCLUSION: A brief community pharmacist intervention
      addressed to depressed patients initiating antidepressant treatment showed a
      probability of being cost-effective of 0.71 and 0.75 in terms of improvement of
      adherence and QALYs, respectively, when compared to usual care. Regular
      implementation of the community pharmacist intervention is not recommended. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00794196.

PMID- 23950968
TI  - Induction of a feed forward pro-apoptotic mechanistic loop by nitric oxide in a
      human breast cancer model.
AB  - We have previously demonstrated that relatively high concentrations of NO [Nitric
      Oxide] as produced by activated macrophages induced apoptosis in the human breast
      cancer cell line, MDA-MB-468. More recently, we also demonstrated the importance
      of endogenous H2O2 in the regulation of growth in human breast cancer cells. In
      the present study we assessed the interplay between exogenously administered NO
      and the endogenously produced reactive oxygen species [ROS] in human breast
      cancer cells and evaluated the mechanism[s] in the induction of apoptosis. To
      this end we identified a novel mechanism by which NO down regulated endogenous
      hydrogen peroxide [H2O2] formation via the down-regulation of superoxide [O2 (.
      )] and the activation of catalase. We further demonstrated the existence of a
      feed forward mechanistic loop involving protein phosphatase 2A [PP2A] and its
      downstream substrate FOXO1 in the induction of apoptosis and the synthesis of
      catalase. We utilized gene silencing of PP2A, FOXO1 and catalase to assess their
      relative importance and key roles in NO mediated apoptosis. This study provides
      the potential for a therapeutic approach in treating breast cancer by targeted
      delivery of NO where NO donors and activators of downstream players could
      initiate a self sustaining apoptotic cascade in breast cancer cells. 

PMID- 23950970
TI  - Development of a new approach to aid in visual identification of murine iPS
      colonies using a fuzzy logic decision support system.
AB  - The a priori identification of induced pluripotent stem cells remains a
      challenge. Being able to quickly identify the most embryonic stem cell-similar
      induced pluripotent stem cells when validating results could help to reduce costs
      and save time. In this context, tools based on non-classic logic can be useful in
      creating aid-systems based on visual criteria. True colonies when viewed at 100x
      magnification have been found to have the following 3 characteristics: a high
      degree of border delineation, a more uniform texture, and the absence of a
      cracked texture. These visual criteria were used for fuzzy logic modeling. We
      investigated the possibility of predicting the presence of alkaline phosphatase
      activity, typical of true induced pluripotent stem cell colonies, after 25
      individuals, with varying degrees of experience in working with murine iPS cells,
      categorized the images of 136 colonies based on visual criteria. Intriguingly,
      the performance evaluation by area under the ROC curve (16 individuals with
      satisfactory performance), Spearman correlation (all statistically significant),
      and Cohen's Kappa agreement analysis (all statistically significant) demonstrates
      that the discriminatory capacity of different evaluators are similar, even those
      who have never cultivated cells. Thus, we report on a new system to facilitate
      visual identification of murine- induced pluripotent stem cell colonies that can
      be useful for staff training and opens the possibility of exploring visual
      characteristics of induced pluripotent stem cell colonies with their functional
      peculiarities. The fuzzy model has been integrated as a web-based tool named
      "2see-iPS" which is freely accessed at http://genetica.incor.usp.br/2seeips/. 

PMID- 23950969
TI  - Molecular and clinical characteristics of clonal complex 59 methicillin-resistant
      Staphylococcus aureus infections in Mainland China.
AB  - Detailed molecular analyses of Clonal Complex 59 (CC59) methicillin-resistant
      Staphylococcus aureus (MRSA) isolates from children in seven major cities across
      Mainland China were examined. A total of 110 CC59 isolates from invasive and non
      invasive diseases were analyzed by multilocus sequence typing (MLST),
      Staphylococcus cassette chromosome mec (SCCmec) typing, staphylococcal protein A
      (spa) typing and pulsed-field gel electrophoresis (PFGE). Antibiotics
      susceptibilities, carriage of plasmids and 42 virulence genes and the expression
      of virulence factors were examined. ST59 (101/110, 91.8%) was the predominant
      sequence type (ST), while single locus variants (SLVs) belonging to ST338 (8/110,
      7.3%) and ST375 (1/110, 0.9%) were obtained. Three SCCmec types were found,
      namely type III (2.7%), type IV (74.5%) and type V (22.7%). Seven spa types
      including t437, which accounted for 87.3%, were determined. Thirteen PFGE types
      were obtained. PFGE types A and B were the major types totally accounting for
      81.8%. The dominant clone was ST59-t437-IVa (65.5%), followed by ST59-t437-V
      (14.5%). The positive rate of luks-PV and lukF-PV PVL encoding (pvl) gene was
      55.5%. Plasmids were detected in 83.6% (92/110) of the strains. The plasmid size
      ranging from 23.4 kb to 50 kb was most prevalent which accounted for 83.7%
      (77/92). A significantly lower expression of hla was found in ST59-t437-IVa
      compared with ST59-t437-V. Among the 110 cases, 61.8% of the patients were less
      than 1 year old. A total of 90 cases (81.8%) were community-associated (CA)
      infections whereas 20 cases (18.2%) were hospital-associated (HA) infections. Out
      of the 110 patients, 36.4% (40/110) were diagnosed with invasive infectious
      diseases in which ST59-t437-IVa accounted for 67.5% (27/40). In brief, ST59-t437
      IVa was proved as the dominant clone in CC59 MRSA strains. The carriage rate of
      pvl gene was high. CC59 MRSA could result in CA and HA infections. The majortiy
      of MRSA infection children were in young age. 

PMID- 23950972
TI  - Acute toxicity of intravenously administered titanium dioxide nanoparticles in
      mice.
AB  - BACKGROUND: With a wide range of applications, titanium dioxide (TiO2)
      nanoparticles (NPs) are manufactured worldwide in large quantities. Recently, in
      the field of nanomedicine, intravenous injection of TiO2 nanoparticulate carriers
      directly into the bloodstream has raised public concerns on their toxicity to
      humans. METHODS: In this study, mice were injected intravenously with a single
      dose of TiO2 NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg). Animal
      mortality, blood biochemistry, hematology, genotoxicity and histopathology were
      investigated 14 days after treatment. RESULTS: Death of mice in the highest dose
      (1387 mg/kg) group was observed at day two after TiO2 NPs injection. At day 7,
      acute toxicity symptoms, such as decreased physical activity and decreased intake
      of food and water, were observed in the highest dose group. Hematological
      analysis and the micronucleus test showed no significant acute hematological or
      genetic toxicity except an increase in the white blood cell (WBC) count among
      mice 645 mg/kg dose group. However, the spleen of the mice showed significantly
      higher tissue weight/body weight (BW) coefficients, and lower liver and kidney
      coefficients in the TiO2 NPs treated mice compared to control. The biochemical
      parameters and histological tissue sections indicated that TiO2 NPs treatment
      could induce different degrees of damage in the brain, lung, spleen, liver and
      kidneys. However, no pathological effects were observed in the heart in TiO2 NPs
      treated mice. CONCLUSIONS: Intravenous injection of TiO2 NPs at high doses in
      mice could cause acute toxicity effects in the brain, lung, spleen, liver, and
      kidney. No significant hematological or genetic toxicity was observed.

PMID- 23950971
TI  - Growth and differentiation factor 3 induces expression of genes related to
      differentiation in a model of cancer stem cells and protects them from retinoic
      acid-induced apoptosis.
AB  - Misexpression of growth factors, particularly those related to stem cell-like
      phenotype, is often observed in several cancer types. It has been found to
      influence parameters of disease progression like cell proliferation,
      differentiation, maintenance of undifferentiated phenotype and modulation of the
      immune system. GDF3 is a TGFB family member associated with pluripotency and
      differentiation during embryonic development that has been previously reported to
      be re-expressed in a number of cancer types. However, its role in tumor
      development and progression has not been clarified yet. In this study we decipher
      the role of GDF3 in an in vitro model of cancer stem cells, NCCIT cells. By
      classical approach to study protein function combined with high-throughput
      technique for transcriptome analysis and differentiation assays we evaluated GDF3
      as a potential therapeutic target. We observed that GDF3 robustly induces a panel
      of genes related to differentiation, including several potent tumor suppressors,
      without impacting the proliferative capacity. Moreover, we report for the first
      time the protective effect of GDF3 against retinoic acid-induced apoptosis in
      cells with stem cell-like properties. Our study implies that blocking of GDF3
      combined with retinoic acid-treatment of solid cancers is a compelling direction
      for further investigations, which can lead to re-design of cancer differentiation
      therapies. 

PMID- 23950973
TI  - An S-type anion channel SLAC1 is involved in cryptogein-induced ion fluxes and
      modulates hypersensitive responses in tobacco BY-2 cells.
AB  - Pharmacological evidence suggests that anion channel-mediated plasma membrane
      anion effluxes are crucial in early defense signaling to induce immune responses
      and hypersensitive cell death in plants. However, their molecular bases and
      regulation remain largely unknown. We overexpressed Arabidopsis SLAC1, an S-type
      anion channel involved in stomatal closure, in cultured tobacco BY-2 cells and
      analyzed the effect on cryptogein-induced defense responses including fluxes of
      Cl(-) and other ions, production of reactive oxygen species (ROS), gene
      expression and hypersensitive responses. The SLAC1-GFP fusion protein was
      localized at the plasma membrane in BY-2 cells. Overexpression of SLAC1 enhanced
      cryptogein-induced Cl(-) efflux and extracellular alkalinization as well as
      rapid/transient and slow/prolonged phases of NADPH oxidase-mediated ROS
      production, which was suppressed by an anion channel inhibitor, DIDS. The
      overexpressor also showed enhanced sensitivity to cryptogein to induce downstream
      immune responses, including the induction of defense marker genes and the
      hypersensitive cell death. These results suggest that SLAC1 expressed in BY-2
      cells mediates cryptogein-induced plasma membrane Cl(-) efflux to positively
      modulate the elicitor-triggered activation of other ion fluxes, ROS as well as a
      wide range of defense signaling pathways. These findings shed light on the
      possible involvement of the SLAC/SLAH family anion channels in cryptogein
      signaling to trigger the plasma membrane ion channel cascade in the plant defense
      signal transduction network. 

PMID- 23950975
TI  - The in vitro mass-produced model mycorrhizal fungus, Rhizophagus irregularis,
      significantly increases yields of the globally important food security crop
      cassava.
AB  - The arbuscular mycorrhizal symbiosis is formed between arbuscular mycorrhizal
      fungi (AMF) and plant roots. The fungi provide the plant with inorganic phosphate
      (P). The symbiosis can result in increased plant growth. Although most global
      food crops naturally form this symbiosis, very few studies have shown that their
      practical application can lead to large-scale increases in food production.
      Application of AMF to crops in the tropics is potentially effective for improving
      yields. However, a main problem of using AMF on a large-scale is producing cheap
      inoculum in a clean sterile carrier and sufficiently concentrated to cheaply
      transport. Recently, mass-produced in vitro inoculum of the model mycorrhizal
      fungus Rhizophagus irregularis became available, potentially making its use
      viable in tropical agriculture. One of the most globally important food plants in
      the tropics is cassava. We evaluated the effect of in vitro mass-produced R.
      irregularis inoculum on the yield of cassava crops at two locations in Colombia.
      A significant effect of R. irregularis inoculation on yield occurred at both
      sites. At one site, yield increases were observed irrespective of P
      fertilization. At the other site, inoculation with AMF and 50% of the normally
      applied P gave the highest yield. Despite that AMF inoculation resulted in
      greater food production, economic analyses revealed that AMF inoculation did not
      give greater return on investment than with conventional cultivation. However,
      the amount of AMF inoculum used was double the recommended dose and was
      calculated with European, not Colombian, inoculum prices. R. irregularis can also
      be manipulated genetically in vitro, leading to improved plant growth. We
      conclude that application of in vitro R. irregularis is currently a way of
      increasing cassava yields, that there is a strong potential for it to be
      economically profitable and that there is enormous potential to improve this
      efficiency further in the future. 

PMID- 23950974
TI  - Multiple sclerosis: modulation of toll-like receptor (TLR) expression by
      interferon-beta includes upregulation of TLR7 in plasmacytoid dendritic cells.
AB  - Interferon-beta is an established treatment for patients with multiple sclerosis
      (MS) but its mechanisms of action are not well understood. Viral infections are a
      known trigger of MS relapses. Toll-like receptors (TLRs) are key components of
      the innate immune system, which sense conserved structures of viruses and other
      pathogens. Effects of interferon-beta on mRNA levels of all known human TLRs
      (TLR1-10) and the TLR adaptor molecule MyD88 were analyzed in peripheral blood
      mononuclear cells (PBMCs) of healthy donors by quantitative real-time PCR and by
      transcriptome analysis in PBMCs of 25 interferon-beta-treated patients with
      relapsing-remitting MS. Regulation of TLR protein expression by interferon-beta
      was investigated by flow cytometry of leukocyte subsets of healthy subjects and
      of untreated, interferon-beta-, or glatiramer acetate-treated patients with MS.
      Interferon-beta specifically upregulated mRNA expression of TLR3, TLR7, and MyD88
      and downregulated TLR9 mRNA in PBMCs of healthy donors as well as in PBMCs of
      patients with MS. Plasmacytoid dendritic cells (pDCs) were identified as the
      major cell type responding to interferon-beta with increased expression of TLR7
      and MyD88 protein. In line with this, expression of TLR7 protein was increased in
      pDCs of interferon-beta-treated, but not untreated or glatiramer acetate-treated
      patients with MS. Interferon-beta-induced upregulation of TLR7 in pDCs is of
      functional relevance since pre-treatment of PBMCs with interferon-beta resulted
      in a strongly increased production of interferon-alpha upon stimulation with the
      TLR7 agonist loxoribine. Flow cytometry confirmed pDCs as the cellular source of
      interferon-alpha production induced by activation of TLR7. Thus, upregulation of
      TLR7 in pDCs and a consequently increased activation of pDCs by TLR7 ligands
      represents a novel immunoregulatory mechanism of interferon-beta. We hypothesize
      that this mechanism could contribute to a reduction of virus-triggered relapses
      in patients with MS. 

PMID- 23950976
TI  - Contribution of common genetic variants to obesity and obesity-related traits in
      mexican children and adults.
AB  - BACKGROUND: Several studies have identified multiple obesity-associated loci
      mainly in European populations. However, their contribution to obesity in other
      ethnicities such as Mexicans is largely unknown. The aim of this study was to
      examine 26 obesity-associated single-nucleotide polymorphisms (SNP) in a sample
      of Mexican mestizos. METHODS: 9 SNPs in biological candidate genes showing
      replications (PPARG, ADRB3, ADRB2, LEPR, GNB3, UCP3, ADIPOQ, UCP2, and NR3C1),
      and 17 SNPs in or near genes associated with obesity in first, second and third
      wave GWAS (INSIG2, FTO, MC4R, TMEM18, FAIM2/BCDIN3, BDNF, SH2B1, GNPDA2, NEGR1,
      KCTD15, SEC16B/RASAL2, NPC1, SFRF10/ETV5, MAF, PRL, MTCH2, and PTER) were
      genotyped in 1,156 unrelated Mexican-Mestizos including 683 cases (441 obese
      class I/II and 242 obese class III) and 473 normal-weight controls. In a second
      stage we selected 12 of the SNPs showing nominal associations with obesity, to
      seek associations with quantitative obesity-related traits in 3 cohorts including
      1,218 Mexican Mestizo children, 945 Mexican Mestizo adults, and 543 Indigenous
      Mexican adults. RESULTS: After adjusting for age, sex and admixture, significant
      associations with obesity were found for 6 genes in the case-control study
      (ADIPOQ, FTO, TMEM18, INSIG2, FAIM2/BCDIN3 and BDNF). In addition, SH2B1 was
      associated only with class I/II obesity and MC4R only with class III obesity.
      SNPs located at or near FAIM2/BCDIN3, TMEM18, INSIG2, GNPDA2 and SEC16B/RASAL2
      were significantly associated with BMI and/or WC in the combined analysis of
      Mexican-mestizo children and adults, and FTO locus was significantly associated
      with increased BMI in Indigenous Mexican populations. CONCLUSIONS: Our findings
      replicate the association of 8 obesity-related SNPs with obesity risk in Mexican
      adults, and confirm the role of some of these SNPs in BMI in Mexican adults and
      children.

PMID- 23950977
TI  - Involvement of right STS in audio-visual integration for affective speech
      demonstrated using MEG.
AB  - Speech and emotion perception are dynamic processes in which it may be optimal to
      integrate synchronous signals emitted from different sources. Studies of audio
      visual (AV) perception of neutrally expressed speech demonstrate supra-additive
      (i.e., where AV>[unimodal auditory+unimodal visual]) responses in left STS to
      crossmodal speech stimuli. However, emotions are often conveyed simultaneously
      with speech; through the voice in the form of speech prosody and through the face
      in the form of facial expression. Previous studies of AV nonverbal emotion
      integration showed a role for right (rather than left) STS. The current study
      therefore examined whether the integration of facial and prosodic signals of
      emotional speech is associated with supra-additive responses in left (cf. results
      for speech integration) or right (due to emotional content) STS. As emotional
      displays are sometimes difficult to interpret, we also examined whether supra
      additive responses were affected by emotional incongruence (i.e., ambiguity).
      Using magnetoencephalography, we continuously recorded eighteen participants as
      they viewed and heard AV congruent emotional and AV incongruent emotional speech
      stimuli. Significant supra-additive responses were observed in right STS within
      the first 250 ms for emotionally incongruent and emotionally congruent AV speech
      stimuli, which further underscores the role of right STS in processing crossmodal
      emotive signals. 

PMID- 23950978
TI  - Long-term impact of community-based information, education and communication
      activities on food hygiene and food safety behaviors in Vietnam: a longitudinal
      study.
AB  - BACKGROUND: Ingestion of contaminated water or food is a major contributor to
      childhood diarrhea in developing countries. In Vietnam, the use of community
      based information, education and communication (IEC) activities could be a
      sustainable strategy to improve food hygiene and food safety behaviors. This
      study thus examined the long-term impact of community-based IEC activities on
      food hygiene and food safety behaviors. METHODS: In this longitudinal study, we
      interviewed caregivers of children aged between six months and four years in
      suburban Hanoi. Baseline data were collected in January 2006 (n = 125). After
      conducting IEC interventions, we collected a 1(st) set of evaluation data in
      January 2007 (n = 132). To examine the long-term impact of the interventions, we
      then collected a 2(nd) set of evaluation data in January 2008 (n = 185). Changes
      in childhood diarrhea prevalence, IEC coverage, and food hygiene and food safety
      behaviors were assessed over a two-year period using bivariate and logistic
      regression analyses. Effective IEC channels were determined through multiple
      linear regression analysis. RESULTS: Childhood diarrhea was significantly reduced
      from 21.6% at baseline to 7.6% at the 1(st) post-intervention evaluation (P =
      0.002), and to 5.9% at the 2(nd) evaluation. Among 17 food hygiene and food
      safety behaviors measured, a total of 11 behaviors were improved or maintained by
      the 2(nd) evaluation. Handwashing after toilet use was significantly improved at
      both evaluation points. Overall, 3 food safety behaviors and 7 food hygiene
      behaviors were found to have significantly improved at the 1(st) and at the 2(nd)
      evaluations, respectively. Flip chart communication administered by community
      groups was identified to be the most effective IEC channel for effecting behavior
      change (P = 0.018). CONCLUSIONS: Flip chart communication administered by
      community groups is effective for improving multiple food hygiene and food safety
      behaviors in sustainable ways, and should be included in water and health
      promotion programs.

PMID- 23950979
TI  - MTB-3, a microtubule plus-end tracking protein (+TIP) of Neurospora crassa.
AB  - The microtubule (MT) "plus end" constitutes the platform for the accumulation of
      a structurally and functionally diverse group of proteins, collectively called
      "MT plus-end tracking proteins" (+TIPs). +TIPs control MT dynamics and link MTs
      to diverse sub-cellular structures. Neurospora crassaMicroTubule Binding protein
      3 (MTB-3) is the homolog of yeast EB1, a highly conserved +TIP. To address the
      function of MTB-3, we examined strains with mtb-3 deletions, and we tagged MTB-3
      with GFP to assess its dynamic behavior. MTB-3-GFP was present as comet-like
      structures distributed more or less homogeneously within the hyphal cytoplasm,
      and moving mainly towards the apex at speeds up to 4* faster than the normal
      hyphal elongation rates. MTB-3-GFP comets were present in all developmental
      stages, but were most abundant in mature hyphae. MTB-3-GFP comets were observed
      moving in anterograde and retrograde direction along the hypha. Retrograde
      movement was also observed as originating from the apical dome. The integrity of
      the microtubular cytoskeleton affects the presence and dynamics of MTB-3-GFP
      comets, while actin does not seem to play a role. The size of MTB-3-GFP comets is
      affected by the absence of dynactin and conventional kinesin. We detected no
      obvious morphological phenotypes in Deltamtb-3 mutants but there were fewer MTs
      in Deltamtb-3, MTs were less bundled and less organized. Compared to WT, both MT
      polymerization and depolymerization rates were significantly decreased in
      Deltamtb-3. In summary, the lack of MTB-3 affects overall growth and
      morphological phenotypes of N. crassa only slightly, but deletion of mtb-3 has
      strong effect on MT dynamics. 

PMID- 23950980
TI  - Association of Dll4/notch and HIF-1a -VEGF signaling in the angiogenesis of
      missed abortion.
AB  - BACKGROUND: Dll4/Notch and HIF-1a-VEGF have been shown to play an important role
      during angiogenesis, but there are no data about their roles and association in
      missed abortion. In this study, we investigated the association of Dll4/Notch and
      HIF-1a-VEGF signaling in missed abortion. METHODS: Women with missed abortion
      (n=27) and healthy controls (n=26) were included in the study. Real-time Reverse
      Transcription-PCR Analyses (RT-PCR) was used to analyze the mRNA levels of
      Dll4/Notch and HIF-1a-VEGF signaling molecules. The protein level for Dll4 was
      measured by immunohistochemistry. RESULTS: Compared with induced abortion, the
      expression of VEGF was statistically reduced while the level of VEGFR1 and Notch1
      was significantly up-regulated in missed abortion. Though other molecules (VEGFR2
      and Dll4) were marginally higher in missed abortion, no statistical difference
      was observed. The expression of HIF-1a was significantly up-regulated, and close
      negatively correlated with VEGF in missed abortion. Both in induced abortion and
      missed abortion, Dll4 was positively correlated with Notch1. CONCLUSIONS: The
      early pregnancy is in a hypoxic environment, this may encourage the angiogenesis,
      but severe hypoxic may inhibit the angiogenesis. Aberrant Dll4/Notch and HIF-1a
      VEGF signaling may have a role in missed abortion.

PMID- 23950981
TI  - Pathway analysis using genome-wide association study data for coronary restenosis
      -a potential role for the PARVB gene.
AB  - BACKGROUND: Coronary restenosis after percutaneous coronary intervention (PCI)
      still remains a significant limitation of the procedure. The causative mechanisms
      of restenosis have not yet been fully identified. The goal of the current study
      was to perform gene-set analysis of biological pathways related to inflammation,
      proliferation, vascular function and transcriptional regulation on coronary
      restenosis to identify novel genes and pathways related to this condition.
      METHODS: The GENetic DEterminants of Restenosis (GENDER) databank contains
      genotypic data of 556,099SNPs of 295 cases with restenosis and 571 matched
      controls. Fifty-four pathways, related to known restenosis-related processes,
      were selected. Gene-set analysis was performed using PLINK, GRASS and ALIGATOR
      software. Pathways with a p<0.01 were fine-mapped and significantly associated
      SNPs were analyzed in an independent replication cohort. RESULTS: Six pathways
      (cell-extracellular matrix (ECM) interactions pathway, IL2 signaling pathway, IL6
      signaling pathway, platelet derived growth factor pathway, vitamin D receptor
      pathway and the mitochondria pathway) were significantly associated in one or two
      of the software packages. Two SNPs in the cell-ECM interactions pathway were
      replicated in an independent restenosis cohort. No replication was obtained for
      the other pathways. CONCLUSION: With these results we demonstrate a potential
      role of the cell-ECM interactions pathway in the development of coronary
      restenosis. These findings contribute to the increasing knowledge of the genetic
      etiology of restenosis formation and could serve as a hypothesis-generating
      effort for further functional studies.

PMID- 23950982
TI  - Combining aspirin with cholecalciferol (vitamin D3)--a potential new tool for
      controlling possum populations.
AB  - The introduced Australian brushtail possum is a major vertebrate pest in New
      Zealand, with impacts on conservation and agriculture being managed largely
      through poisoning operations. Cholecalciferol (vitamin D3) is registered for use
      in controlling possums and despite its many advantages it is expensive and
      relatively inhumane. Combination of a high proportion of aspirin with a low
      proportion of cholecalciferol was effective in killing high proportions of groups
      of acclimatised, caged possums: this is attributed to both an unexpectedly high
      toxicity of the type of cholecalciferol used, and a proposed synergistic
      mechanism between the two compounds. Death was caused by localised damage to
      heart ventricles by aspirin, and inhibition of tissue repair by both aspirin and
      cholecalciferol. The observed toxicosis had lower impact on the welfare of
      possums than either compound administered alone, particularly aspirin alone.
      Residue analyses of bait remains in the GI tract suggested a low risk of
      secondary poisoning by either compound. The combination of cholecalciferol and
      aspirin has the potential to meet key requirements of cost-effectiveness and
      humaneness in controlling possum populations, but the effect of the combination
      in non-target species has yet to be tested. 

PMID- 23950983
TI  - Direct detection of alternative open reading frames translation products in human
      significantly expands the proteome.
AB  - A fully mature mRNA is usually associated to a reference open reading frame
      encoding a single protein. Yet, mature mRNAs contain unconventional alternative
      open reading frames (AltORFs) located in untranslated regions (UTRs) or
      overlapping the reference ORFs (RefORFs) in non-canonical +2 and +3 reading
      frames. Although recent ribosome profiling and footprinting approaches have
      suggested the significant use of unconventional translation initiation sites in
      mammals, direct evidence of large-scale alternative protein expression at the
      proteome level is still lacking. To determine the contribution of alternative
      proteins to the human proteome, we generated a database of predicted human
      AltORFs revealing a new proteome mainly composed of small proteins with a median
      length of 57 amino acids, compared to 344 amino acids for the reference proteome.
      We experimentally detected a total of 1,259 alternative proteins by mass
      spectrometry analyses of human cell lines, tissues and fluids. In plasma and
      serum, alternative proteins represent up to 55% of the proteome and may be a
      potential unsuspected new source for biomarkers. We observed constitutive co
      expression of RefORFs and AltORFs from endogenous genes and from transfected
      cDNAs, including tumor suppressor p53, and provide evidence that out-of-frame
      clones representing AltORFs are mistakenly rejected as false positive in cDNAs
      screening assays. Functional importance of alternative proteins is strongly
      supported by significant evolutionary conservation in vertebrates, invertebrates,
      and yeast. Our results imply that coding of multiple proteins in a single gene by
      the use of AltORFs may be a common feature in eukaryotes, and confirm that
      translation of unconventional ORFs generates an as yet unexplored proteome. 

PMID- 23950984
TI  - Obesity impairs lymphatic fluid transport and dendritic cell migration to lymph
      nodes.
AB  - INTRODUCTION: Obesity is a major cause of morbidity and mortality resulting in
      pathologic changes in virtually every organ system. Although the cardiovascular
      system has been a focus of intense study, the effects of obesity on the lymphatic
      system remain essentially unknown. The purpose of this study was to identify the
      pathologic consequences of diet induced obesity (DIO) on the lymphatic system.
      METHODS: Adult male wild-type or RAG C57B6-6J mice were fed a high fat (60%) or
      normal chow diet for 8-10 weeks followed by analysis of lymphatic transport
      capacity. In addition, we assessed migration of dendritic cells (DCs) to local
      lymph nodes, lymph node architecture, and lymph node cellular make up. RESULTS:
      High fat diet resulted in obesity in both wild-type and RAG mice and
      significantly impaired lymphatic fluid transport and lymph node uptake;
      interestingly, obese wild-type but not obese RAG mice had significantly impaired
      migration of DCs to the peripheral lymph nodes. Obesity also resulted in
      significant changes in the macro and microscopic anatomy of lymph nodes as
      reflected by a marked decrease in size of inguinal lymph nodes (3.4-fold),
      decreased number of lymph node lymphatics (1.6-fold), loss of follicular pattern
      of B cells, and dysregulation of CCL21 expression gradients. Finally, obesity
      resulted in a significant decrease in the number of lymph node T cells and
      increased number of B cells and macrophages. CONCLUSIONS: Obesity has significant
      negative effects on lymphatic transport, DC cell migration, and lymph node
      architecture. Loss of T and B cell inflammatory reactions does not protect from
      impaired lymphatic fluid transport but preserves DC migration capacity. Future
      studies are needed to determine how the interplay between diet, obesity, and the
      lymphatic system modulate systemic complications of obesity.

PMID- 23950985
TI  - Homology modeling of the CheW coupling protein of the chemotaxis signaling
      complex.
AB  - Homology models of the E. coli and T. maritima chemotaxis protein CheW were
      constructed to assess the quality of structural predictions and their
      applicability in chemotaxis research: i) a model of E. coli CheW was constructed
      using the T. maritima CheW NMR structure as a template, and ii) a model of T.
      maritima CheW was constructed using the E. coli CheW NMR structure as a template.
      The conformational space accessible to the homology models and to the NMR
      structures was investigated using molecular dynamics and Monte Carlo simulations.
      The results show that even though static homology models of CheW may be partially
      structurally different from their corresponding experimentally determined
      structures, the conformational space they can access through their dynamic
      variations can be similar, for specific regions of the protein, to that of the
      experimental NMR structures. When CheW homology models are allowed to explore
      their local accessible conformational space, modeling can provide a rational path
      to predicting CheW interactions with the MCP and CheA proteins of the chemotaxis
      complex. Homology models of CheW (and potentially, of other chemotaxis proteins)
      should be seen as snapshots of an otherwise larger ensemble of accessible
      conformational space. 

PMID- 23950986
TI  - Population structure and dispersal patterns within and between Atlantic and
      Mediterranean populations of a large-range pelagic seabird.
AB  - Dispersal is critically linked to the demographic and evolutionary trajectories
      of populations, but in most seabird species it may be difficult to estimate.
      Using molecular tools, we explored population structure and the spatial dispersal
      pattern of a highly pelagic but philopatric seabird, the Cory's shearwater
      Calonectris diomedea. Microsatellite fragments were analysed from samples
      collected across almost the entire breeding range of the species. To help
      disentangle the taxonomic status of the two subspecies described, the Atlantic
      form C. d. borealis and the Mediterranean form C. d. diomedea, we analysed
      genetic divergence between subspecies and quantified both historical and recent
      migration rates between the Mediterranean and Atlantic basins. We also searched
      for evidence of isolation by distance (IBD) and addressed spatial patterns of
      gene flow. We found a low genetic structure in the Mediterranean basin.
      Conversely, strong genetic differentiation appeared in the Atlantic basin. Even
      if the species was mostly philopatric (97%), results suggest recent dispersal
      between basins, especially from the Atlantic to the Mediterranean (aprox. 10% of
      migrants/generation across the last two generations). Long-term gene flow
      analyses also suggested an historical exchange between basins (about 70
      breeders/generation). Spatial analysis of genetic variation indicates that
      distance is not the main factor in shaping genetic structure in this species.
      Given our results we recommend gathering more data before concluded whether these
      taxa should be treated as two species or subspecies. 

PMID- 23950987
TI  - Improved bone morphogenetic protein-2 retention in an injectable collagen matrix
      using bifunctional peptides.
AB  - To promote healing of many orthopedic injuries, tissue engineering approaches are
      being developed that combine growth factors such as Bone Morphogenetic Proteins
      (BMP) with biomaterial carriers. Although these technologies have shown great
      promise, they still face limitations. We describe a generalized approach to
      create target-specific modular peptides that bind growth factors to implantable
      biomaterials. These bifunctional peptide coatings provide a novel way to modulate
      biology on the surface of an implant. Using phage display techniques, we have
      identified peptides that bind with high affinity to BMP-2. The peptides that bind
      to BMP-2 fall into two different sequence clusters. The first cluster of peptide
      sequences contains the motif W-X-X-F-X-X-L (where X can be any amino acid) and
      the second cluster contains the motif F-P-L-K-G. We have synthesized bifunctional
      peptide linkers that contain BMP-2 and collagen-binding domains. Using a rat
      ectopic bone formation model, we have injected rhBMP-2 into a collagen matrix
      with or without a bifunctional BMP-2: collagen peptide (BC-1). The presence of BC
      1 significantly increased osteogenic cellular activity, the area of bone formed,
      and bone maturity at the site of injection. Our results suggest that bifunctional
      peptides that can simultaneously bind to a growth factor and an implantable
      biomaterial can be used to control the delivery and release of growth factors at
      the site of implantation. 

PMID- 23950988
TI  - A genome-wide survey of highly expressed non-coding RNAs and biological
      validation of selected candidates in Agrobacterium tumefaciens.
AB  - Agrobacterium tumefaciens is a plant pathogen that has the natural ability of
      delivering and integrating a piece of its own DNA into plant genome. Although
      bacterial non-coding RNAs (ncRNAs) have been shown to regulate various biological
      processes including virulence, we have limited knowledge of how Agrobacterium
      ncRNAs regulate this unique inter-Kingdom gene transfer. Using whole
      transcriptome sequencing and an ncRNA search algorithm developed for this work,
      we identified 475 highly expressed candidate ncRNAs from A. tumefaciens C58,
      including 101 trans-encoded small RNAs (sRNAs), 354 antisense RNAs (asRNAs), 20
      5' untranslated region (UTR) leaders including a RNA thermosensor and 6
      riboswitches. Moreover, transcription start site (TSS) mapping analysis revealed
      that about 51% of the mapped mRNAs have 5' UTRs longer than 60 nt, suggesting
      that numerous cis-acting regulatory elements might be encoded in the A.
      tumefaciens genome. Eighteen asRNAs were found on the complementary strands of
      virA, virB, virC, virD, and virE operons. Fifteen ncRNAs were induced and 7 were
      suppressed by the Agrobacterium virulence (vir) gene inducer acetosyringone (AS),
      a phenolic compound secreted by the plants. Interestingly, fourteen of the AS
      induced ncRNAs have putative vir box sequences in the upstream regions. We
      experimentally validated expression of 36 ncRNAs using Northern blot and Rapid
      Amplification of cDNA Ends analyses. We show functional relevance of two 5' UTR
      elements: a RNA thermonsensor (C1_109596F) that may regulate translation of the
      major cold shock protein cspA, and a thi-box riboswitch (C1_2541934R) that may
      transcriptionally regulate a thiamine biosynthesis operon, thiCOGG. Further
      studies on ncRNAs functions in this bacterium may provide insights and strategies
      that can be used to better manage pathogenic bacteria for plants and to improve
      Agrobacterum-mediated plant transformation. 

PMID- 23950989
TI  - First report of Angiostrongylus cantonensis (Nematoda: Angiostrongylidae)
      infections in invasive rodents from five islands of the Ogasawara Archipelago,
      Japan.
AB  - BACKGROUND: Angiostrongylus cantonensis (Chen, 1935) is a parasite of murid
      rodents and causative agent of human neuro-angiostrongyliasis. In 2011, the
      Ogasawara Islands in the western North Pacific were assigned a World Natural
      Heritage site status. The occurrence of A. cantonensis is well documented in the
      Chichijima, Hahajima, and Anijima Islands. However, the occurrence of A.
      cantonensis in the other islands of the Ogasawara Islands has not been reported.
      METHODOLOGY/PRINCIPAL FINDINGS: Between March 2010 and July 2011, 57 Rattus
      norvegicus and 79 R. rattus were collected from 9 islands (the Hahajima group:
      Anejima, Imoutojima, Meijima, Mukohjima, and Hirajima; Chichijima group:
      Minamijima; Mukojima group: Nakoudojima and Yomejima; and Iwojima group:
      Iwojima). Adult nematodes were found in the pulmonary artery of 46 R. norvegicus
      collected in the 5 islands of the Hahajima group (Anejima, Meijima, Imoutojima,
      Hrajima, and Mukohjima Islands). These nematodes were identified by molecular
      analysis as A. cantonensis. Comparison of the mitochondrial DNA sequences
      confirmed that all the samples from the Ogasawara Islands shared only a single
      lineage of A. cantonensis, which has been previously detected in the Okinawa,
      Hawaii, and Brazil. CONCLUSIONS/SIGNIFICANCE: We describe new endemic foci of rat
      angiostrongyliasis in the Hahajima group (Anejima, Meijima, Imoutojima, Hirajima,
      and Mukohjima Islands) of the Ogasawara Islands. These findings indicate that the
      endemic foci of A. cantonensis are widely distributed in the Ogasawara Islands.
      Although human cases have not yet been reported in the Ogasawara Islands, the
      widespread detection of A. cantonensis could be of importance from the
      perspective of public health.

PMID- 23950990
TI  - Contribution of 32 GWAS-identified common variants to severe obesity in European
      adults referred for bariatric surgery.
AB  - The prevalence of severe obesity, defined as body mass index (BMI) >= 35.0
      kg/m(2), is rising rapidly. Given the disproportionately high health burden and
      healthcare costs associated with this condition, understanding the underlying
      aetiology, including predisposing genetic factors, is a biomedical research
      priority. Previous studies have suggested that severe obesity represents an
      extreme tail of the population BMI variation, reflecting shared genetic factors
      operating across the spectrum. Here, we sought to determine whether a panel of 32
      known common obesity-susceptibility variants contribute to severe obesity in
      patients (n = 1,003, mean BMI 48.4 +/- 8.1 kg/m(2)) attending bariatric surgery
      clinics in two European centres. We examined the effects of these 32 common
      variants on obesity risk and BMI, both as individual markers and in combination
      as a genetic risk score, in a comparison with normal-weight controls (n = 1,809,
      BMI 18.0-24.9 kg/m(2)); an approach which, to our knowledge, has not been
      previously undertaken in the setting of a bariatric clinic. We found strong
      associations with severe obesity for SNP rs9939609 within the FTO gene (P = 9.3 *
      10(-8)) and SNP rs2815752 near the NEGR1 gene (P = 3.6 * 10(-4)), and
      directionally consistent nominal associations (P<0.05) for 12 other SNPs. The
      genetic risk score associated with severe obesity (P = 8.3 * 10(-11)) but, within
      the bariatric cohort, this score did not associate with BMI itself (P = 0.264).
      Our results show significant effects of individual BMI-associated common variants
      within a relatively small sample size of bariatric patients. Furthermore, the
      burden of such low-penetrant risk alleles contributes to severe obesity in this
      population. Our findings support that severe obesity observed in bariatric
      patients represents an extreme tail of the population BMI variation. Moreover,
      future genetic studies focused on bariatric patients may provide valuable
      insights into the pathogenesis of obesity at a population level.

PMID- 23950991
TI  - 532 nm low-power laser irradiation recovers gamma-secretase inhibitor-mediated
      cell growth suppression and promotes cell proliferation via Akt signaling.
AB  - BACKGROUND AND OBJECTIVE: The gamma-secretase inhibitor (GSI) has been shown to
      inhibit expression of amyloid beta (Abeta), but GSI also has a side effect of
      reducing cell survival. Since low-power laser irradiation (LLI) has been known to
      promote cell survival, we examined whether 532 nm LLI can rescue the GSI side
      effect or not. STUDY DESIGN/MATERIALS AND METHODS: The human-derived glioblastoma
      cells (A-172) were cultured in 35 mm culture dishes or 96-well plate. The center
      of dish or selected wells was irradiated with 532 nm laser (Nd:YVO4, CW, 60 mW)
      for 20, 40 and 60 min, respectively. The irradiated cells were photographed at
      immediately after, 24 and 48 h later and counted. GSI was supplemented in medium
      3 h before LLI. The MTT assay was also used to estimate viable cells at 48 h
      after irradiation. The expression of phosphorylated Akt (p-Akt) or phosphorylated
      PTEN (p-PTEN) was examined by immunofluorescent staining and measured by
      fluorescence intensity using the software (BZ-9000, KEYENCE, Japan). RESULTS: GSI
      application depressed cell proliferation as well as cell survival compared to
      control. GSI down-regulated Abeta but up-regulated p-PTEN and suppressed p-Akt.
      Application of 532 nm LLI in the presence of GSI significantly recovered the GSI
      mediated effects, i.e., LLI could decrease elevated p-PTEN, while increased p-Akt
      expression with keeping Abeta suppression. The LLI effects had a dose-dependency.
      CONCLUSION: We confirmed that GSI potently suppressed intracellular Abeta and
      decreased cell survival. We conclude that a combination of GSI application and
      532 nm LLI can increase cell proliferation via Akt activation while keeping PTEN
      and Abeta suppressed.

PMID- 23950993
TI  - Early Cambrian pentamerous cubozoan embryos from South China.
AB  - BACKGROUND: Extant cubozoans are voracious predators characterized by their
      square shape, four evenly spaced outstretched tentacles and well-developed eyes.
      A few cubozoan fossils are known from the Middle Cambrian Marjum Formation of
      Utah and the well-known Carboniferous Mazon Creek Formation of Illinois.
      Undisputed cubozoan fossils were previously unknown from the early Cambrian; by
      that time probably all representatives of the living marine phyla, especially
      those of basal animals, should have evolved. METHODS: Microscopic fossils were
      recovered from a phosphatic limestone in the Lower Cambrian Kuanchuanpu Formation
      of South China using traditional acetic-acid maceration. Seven of the pre-hatched
      pentamerous cubozoan embryos, each of which bears five pairs of subumbrellar
      tentacle buds, were analyzed in detail through computed microtomography (Micro
      CT) and scanning electron microscopy (SEM) without coating. RESULTS: The figured
      microscopic fossils are unequivocal pre-hatching embryos based on their spherical
      fertilization envelope and the enclosed soft-tissue that has preserved key
      anatomical features arranged in perfect pentaradial symmetry, allowing detailed
      comparison with modern cnidarians, especially medusozoans. A combination of
      features, such as the claustrum, gonad-lamella, suspensorium and velarium
      suspended by the frenula, occur exclusively in the gastrovascular system of
      extant cubozoans, indicating a cubozoan affinity for these fossils. Additionally,
      the interior anatomy of these embryonic cubozoan fossils unprecedentedly exhibits
      the development of many new septum-derived lamellae and well-partitioned gastric
      pockets unknown in living cubozoans, implying that ancestral cubozoans had
      already evolved highly specialized structures displaying unexpected complexity at
      the dawn of the Cambrian. The well-developed endodermic lamellae and gastric
      pockets developed in the late embryonic stages of these cubozoan fossils are
      comparable with extant pelagic juvenile cubomedusae rather than sessile
      cubopolyps, whcih indicates a direct development in these fossil taxa, lacking
      characteristic stages of a typical cnidarian metagenesis such as planktonic
      planula and sessile polyps.

PMID- 23950992
TI  - Dendritic cells from Crohn's disease patients show aberrant STAT1 and STAT3
      signaling.
AB  - Abnormalities of dendritic cells (DCs) and STAT proteins have been reported in
      Crohn's disease (CD). Studies on JAK/STAT signaling in DCs are, however, lacking
      in CD. We applied a flowcytometric single-cell-based phosphoepitope assay to
      evaluate STAT1 and STAT3 pathways in DC subsets from CD patients. In addition,
      circulating DC counts were determined, together with the activation-related
      immunophenotype. We found that IL-6- and IFN-alpha-induced STAT3 phosphorylation
      and IFN-alpha-induced STAT1 phosphorylation were impaired in plasmacytoid DCs
      (pDCs) from CD patients (P = 0.005, P = 0.013, and P = 0.006, respectively). In
      myeloid DCs (mDCs), IFN-alpha-induced STAT1 and STAT3 phosphorylation were
      attenuated (P<0.001 and P = 0.048, respectively), but IL-10-induced STAT3
      phosphorylation was enhanced (P = 0.026). IFN-gamma-induced STAT1 signaling was
      intact in both DC subtypes. Elevated plasma IL-6 levels were detected in CD (P =
      0.004), which strongly correlated with disease activity (rho = 0.690, P<0.001)
      but not with IL-6-induced STAT3 phosphorylation. The numbers of pDCs and BDCA3+
      mDCs were decreased, and CD40 expression on CD1c+ mDCs was increased in CD. When
      elucidating the effect of IL-6 signaling on pDC function, we observed that IL-6
      treatment of healthy donor pDCs affected the maturation of and modified the T
      cell priming by pDCs, favoring Th2 over Th1 type of response and the expression
      of IL-10 in T cells. Our results implicate DC signaling in human CD. Reduced IL-6
      responsiveness in pDCs, together with the attenuated IFN-alpha-induced signaling
      in both DC subtypes, may contribute to the immunological dysregulation in CD
      patients.

PMID- 23950994
TI  - Validation of the Los Angeles pre-hospital stroke screen (LAPSS) in a Chinese
      urban emergency medical service population.
AB  - BACKGROUND AND PURPOSE: Early and accurate diagnosis of stroke by emergency
      medical service (EMS) paramedics is critical for reducing pre-hospital delays.
      The Los Angeles pre-hospital stroke screen (LAPSS) has been widely used as a
      validated screening tool for early identifying stroke patients by EMS paramedics.
      However, validation of LAPSS has never been performed in Chinese stroke
      population. This study is aimed to verify the LAPSS for early identifying stroke
      patients in a Chinese urban EMS. METHODS: 76 paramedics of five urban first aid
      stations attached to Beijing 120 EMS were involved. The paramedics were trained
      by professionals to quickly screen patients based on LAPSS. Potential "target
      stroke" individuals who met the base LAPSS screen criteria were identified.
      Sensitivity and specificity analyses of the LAPSS were calculated. RESULTS: From
      June 10, 2009 to June 10, 2010, paramedics transported a total of 50,220
      patients. 1550 patients who met the baseline screen criteria were identified as
      the potential "target stroke" population. 1130 patients had the completed LAPSS
      information datasheet and 997 patients were clinically diagnosed with stroke. The
      average time of completing the LAPSS was 4.3+/-3.0 minutes (median, 5 minutes).
      The sensitivity and specificity of the LAPSS in this study was 78.44% and 90.22%,
      respectively. After adjusting for age factor by excluding patients of >45 years
      old, the sensitivity was significantly increased to 82.95% with specificity
      unchanged. CONCLUSION: The paramedics of Beijing 120 EMS could efficiently use
      LAPSS as a screening tool for early identifying stroke patients. While the
      sensitivity of LAPSS in Chinese urban patient population was lower than those
      reported in previous LAPSS validation studies, the specificity was consistent
      with these studies. After excluded the item of "Age>45 years", the sensitivity
      was improved.

PMID- 23950995
TI  - Hepatitis C virus induced miR200c down modulates FAP-1, a negative regulator of
      Src signaling and promotes hepatic fibrosis.
AB  - Hepatitis C virus (HCV) induced liver disease is the leading indication for liver
      transplantation (LTx). Reinfection and accelerated development of fibrosis is a
      universal phenomenon following LTx. The molecular events that lead to fibrosis
      following HCV infection still remains poorly defined. In this study, we
      determined microRNA (miRNA) and mRNA expression profiles in livers from chronic
      HCV patients and normals using microarrays. Using Genego software and pathway
      finder we performed an interactive analysis to identify target genes that are
      modulated by miRNAs. 22 miRNAs were up regulated (>2 fold) and 35 miRNAs were
      down regulated (>2fold) compared to controls. Liver from HCV patients
      demonstrated increased expression of 306 genes (>3 fold) and reduced expression
      of 133 genes (>3 fold). Combinatorial analysis of the networks modulated by the
      miRNAs identified regulation of the phospholipase C pathway (miR200c, miR20b, and
      miR31through cellular proto-oncogene tyrosine-protein kinase Src (cSrc)),
      response to growth factors and hormones (miR141, miR107 and miR200c through
      peroxisome proliferator-activated receptor alpha and extracellular-signal
      regulated kinases, and regulation of cellular proliferation (miR20b, miR10b, and
      miR141 through cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1
      p21). Real time PCR (RT-PCR) validation of the miRNA in HCV infected livers
      demonstrated a 3.3 +/-0.9 fold increase in miR200c. In vitro transfection of
      fibroblasts with miR200c resulted in a 2.2 fold reduction in expression of
      tyrosine-protein phosphatase non-receptor type 13 or FAS associated phosphatase 1
      (FAP-1) and 2.3 fold increase in expression of cSrc. miR200c transfection
      resulted in significant increases in expression of collagen and fibroblast growth
      factor (2.8 and 3.4 fold, p<0.05). Therefore, we propose that HCV induced
      increased expression of miR200c can down modulate the expression of FAP1, a
      critical regulator of Src and MAP kinase pathway that play an important role in
      the production of fibrogenic growth factors and development of fibrosis. 

PMID- 23950996
TI  - A tribute to disorder in the genome of the bloom-forming freshwater
      cyanobacterium Microcystis aeruginosa.
AB  - Microcystis aeruginosa is one of the most common bloom-forming cyanobacteria in
      freshwater ecosystems worldwide. This species produces numerous secondary
      metabolites, including microcystins, which are harmful to human health. We
      sequenced the genomes of ten strains of M. aeruginosa in order to explore the
      genomic basis of their ability to occupy varied environments and proliferate. Our
      findings show that M. aeruginosa genomes are characterized by having a large open
      pangenome, and that each genome contains similar proportions of core and flexible
      genes. By comparing the GC content of each gene to the mean value of the whole
      genome, we estimated that in each genome, around 11% of the genes seem to result
      from recent horizontal gene transfer events. Moreover, several large gene
      clusters resulting from HGT (up to 19 kb) have been found, illustrating the
      ability of this species to integrate such large DNA molecules. It appeared also
      that all M. aeruginosa displays a large genomic plasticity, which is
      characterized by a high proportion of repeat sequences and by low synteny values
      between the strains. Finally, we identified 13 secondary metabolite gene
      clusters, including three new putative clusters. When comparing the genomes of
      Microcystis and Prochlorococcus, one of the dominant picocyanobacteria living in
      marine ecosystems, our findings show that they are characterized by having almost
      opposite evolutionary strategies, both of which have led to ecological success in
      their respective environments. 

PMID- 23950997
TI  - Impact loading and locomotor-respiratory coordination significantly influence
      breathing dynamics in running humans.
AB  - Locomotor-respiratory coupling (LRC), phase-locking between breathing and
      stepping rhythms, occurs in many vertebrates. When quadrupedal mammals gallop,
      1?1 stride per breath coupling is necessitated by pronounced mechanical
      interactions between locomotion and ventilation. Humans show more flexibility in
      breathing patterns during locomotion, using LRC ratios of 2?1, 2.5?1, 3?1, or 4?1
      and sometimes no coupling. Previous studies provide conflicting evidence on the
      mechanical significance of LRC in running humans. Some studies suggest LRC
      improves breathing efficiency, but others suggest LRC is mechanically
      insignificant because 'step-driven flows' (ventilatory flows attributable to step
      induced forces) contribute a negligible fraction of tidal volume. Yet, although
      step-driven flows are brief, they cause large fluctuations in ventilatory flow.
      Here we test the hypothesis that running humans use LRC to minimize antagonistic
      effects of step-driven flows on breathing. We measured locomotor-ventilatory
      dynamics in 14 subjects running at a self-selected speed (2.6+/-0.1 ms(-1)) and
      compared breathing dynamics in their naturally 'preferred' and 'avoided'
      entrainment patterns. Step-driven flows occurred at 1-2X step frequency with peak
      magnitudes of 0.97+/-0.45 Ls(-1) (mean +/-S.D). Step-driven flows varied
      depending on ventilatory state (high versus low lung volume), suggesting state
      dependent changes in compliance and damping of thoraco-abdominal tissues.
      Subjects naturally preferred LRC patterns that minimized antagonistic
      interactions and aligned ventilatory transitions with assistive phases of the
      step. Ventilatory transitions initiated in 'preferred' phases within the step
      cycle occurred 2x faster than those in 'avoided' phases. We hypothesize that
      humans coordinate breathing and locomotion to minimize antagonistic loading of
      respiratory muscles, reduce work of breathing and minimize rate of fatigue.
      Future work could address the potential consequences of locomotor-ventilatory
      interactions for elite endurance athletes and individuals who are overweight or
      obese, populations in which respiratory muscle fatigue can be limiting. 

PMID- 23950998
TI  - Diverse secreted effectors are required for Salmonella persistence in a mouse
      infection model.
AB  - Salmonella enterica serovar Typhimurium causes typhoid-like disease in mice and
      is a model of typhoid fever in humans. One of the hallmarks of typhoid is
      persistence, the ability of the bacteria to survive in the host weeks after
      infection. Virulence factors called effectors facilitate this process by direct
      transfer to the cytoplasm of infected cells thereby subverting cellular
      processes. Secretion of effectors to the cell cytoplasm takes place through
      multiple routes, including two separate type III secretion (T3SS) apparati as
      well as outer membrane vesicles. The two T3SS are encoded on separate
      pathogenicity islands, SPI-1 and -2, with SPI-1 more strongly associated with the
      intestinal phase of infection, and SPI-2 with the systemic phase. Both T3SS are
      required for persistence, but the effectors required have not been systematically
      evaluated. In this study, mutations in 48 described effectors were tested for
      persistence. We replaced each effector with a specific DNA barcode sequence by
      allelic exchange and co-infected with a wild-type reference to calculate the
      ratio of wild-type parent to mutant at different times after infection. The
      competitive index (CI) was determined by quantitative PCR in which primers that
      correspond to the barcode were used for amplification. Mutations in all but seven
      effectors reduced persistence demonstrating that most effectors were required.
      One exception was CigR, a recently discovered effector that is widely conserved
      throughout enteric bacteria. Deletion of cigR increased lethality, suggesting
      that it may be an anti-virulence factor. The fact that almost all Salmonella
      effectors are required for persistence argues against redundant functions. This
      is different from effector repertoires in other intracellular pathogens such as
      Legionella. 

PMID- 23950999
TI  - Establishment of a novel murine model of ischemic cardiomyopathy with multiple
      diffuse coronary lesions.
AB  - OBJECTIVES: Atherosclerotic lesions of the coronary arteries are the pathological
      basis for myocardial infarction and ischemic cardiomyopathy. Progression of heart
      failure after myocardial infarction is associated with cardiac remodeling, which
      has been studied by means of coronary ligation in mice. However, this ligation
      model requires excellent techniques. Recently, a new murine model, HypoE mouse
      was reported to exhibit atherogenic Paigen diet-induced coronary atherosclerosis
      and myocardial infarction; however, the HypoE mice died too early to make
      possible investigation of cardiac remodeling. Therefore, we aimed to modify the
      HypoE mouse model to establish a novel model for ischemic cardiomyopathy caused
      by atherosclerotic lesions, which the ligation model does not exhibit. METHODS
      AND RESULTS: In our study, the sustained Paigen diet for the HypoE mice was
      shortened to 7 or 10 days, allowing the mice to survive longer. The 7-day Paigen
      diet intervention starting when the mice were 8 weeks old was adequate to permit
      the mice to survive myocardial infarction. Our murine model, called the "modified
      HypoE mouse", was maintained until 8 weeks, with a median survival period of 36
      days, after the dietary intervention (male, n = 222). Echocardiography
      demonstrated that the fractional shortening 2 weeks after the Paigen diet (n =
      14) significantly decreased compared with that just before the Paigen diet (n =
      6) (31.4+/-11.9% vs. 54.4+/-2.6%, respectively, P<0.01). Coronary angiography
      revealed multiple diffuse lesions. Cardiac remodeling and fibrosis were
      identified by serial analyses of cardiac morphological features and mRNA
      expression levels in tissue factors such as MMP-2, MMP-9, TIMP-1, collagen-1, and
      TGF-beta. CONCLUSION: Modified HypoE mice are a suitable model for ischemic
      cardiomyopathy with multiple diffuse lesions and may be considered as a novel and
      convenient model for investigations of cardiac remodeling on a highly atherogenic
      background.

PMID- 23951000
TI  - The power of auditory-motor synchronization in sports: enhancing running
      performance by coupling cadence with the right beats.
AB  - Acoustic stimuli, like music and metronomes, are often used in sports. Adjusting
      movement tempo to acoustic stimuli (i.e., auditory-motor synchronization) may be
      beneficial for sports performance. However, music also possesses motivational
      qualities that may further enhance performance. Our objective was to examine the
      relative effects of auditory-motor synchronization and the motivational impact of
      acoustic stimuli on running performance. To this end, 19 participants ran to
      exhaustion on a treadmill in 1) a control condition without acoustic stimuli, 2)
      a metronome condition with a sequence of beeps matching participants' cadence
      (synchronization), and 3) a music condition with synchronous motivational music
      matched to participants' cadence (synchronization+motivation). Conditions were
      counterbalanced and measurements were taken on separate days. As expected, time
      to exhaustion was significantly longer with acoustic stimuli than without.
      Unexpectedly, however, time to exhaustion did not differ between metronome and
      motivational music conditions, despite differences in motivational quality.
      Motivational music slightly reduced perceived exertion of sub-maximal running
      intensity and heart rates of (near-)maximal running intensity. The beat of the
      stimuli -which was most salient during the metronome condition- helped runners to
      maintain a consistent pace by coupling cadence to the prescribed tempo. Thus,
      acoustic stimuli may have enhanced running performance because runners worked
      harder as a result of motivational aspects (most pronounced with motivational
      music) and more efficiently as a result of auditory-motor synchronization (most
      notable with metronome beeps). These findings imply that running to motivational
      music with a very prominent and consistent beat matched to the runner's cadence
      will likely yield optimal effects because it helps to elevate physiological
      effort at a high perceived exertion, whereas the consistent and correct cadence
      induced by auditory-motor synchronization helps to optimize running economy. 

PMID- 23951001
TI  - Macrogenomic evidence for the origin of the black fly Simulium suzukii (Diptera:
      Simuliidae) on Okinawa Island, Japan.
AB  - To determine the geographic origin of the black fly Simulium suzukii on Okinawa
      Island, Japan, macrogenomic profiles derived from its polytene chromosomes were
      compared with those of mainland and other insular populations of S. suzukii and
      of the isomorphic Simulium tani species complex. The Okinawan population is a
      chromosomally unique cytoform, designated 'D,' which is essentially monomorphic
      and differs by about 27 fixed rearrangements from the chromosomal standard
      sequence for the subgenus Simulium and by two fixed differences from its nearest
      known relative, representing the type of S. suzukii, on the main islands of
      Japan. Chromosomal band sequences revealed two additional, sympatric cytoforms of
      S. suzukii, designated 'A' and 'B,' each with species status, in Korea, and a
      third cytoform, designated 'C,' on Hokkaido, Japan. A new cytoform, 'K,' of S.
      tani from Malaysia, representing the type of S. tani, is more closely related to
      cytoforms in Thailand, as are populations from Taiwan previously treated as S.
      suzukii but more closely aligned with S. tani and newly recognized as cytoform
      'L' of the latter nominal species. Rooting of chromosomal band sequences by
      outgroup comparisons allowed directionality of chromosomal rearrangements to be
      established, enabling phylogenetic inference of cytoforms. Of 41 macrogenomic
      rearrangements discovered in the five new cytoforms, four provide evidence for a
      stepwise origin of the Okinawan population from populations characteristic of the
      main islands of Japan. The macrogenomic approach applied to black flies on
      Okinawa Island illustrates its potential utility in defining source areas for
      other species of flies including those that might pose medical and veterinary
      risks. 

PMID- 23951002
TI  - The EBM-DPSER conceptual model: integrating ecosystem services into the DPSIR
      framework.
AB  - There is a pressing need to integrate biophysical and human dimensions science to
      better inform holistic ecosystem management supporting the transition from single
      species or single-sector management to multi-sector ecosystem-based management.
      Ecosystem-based management should focus upon ecosystem services, since they
      reflect societal goals, values, desires, and benefits. The inclusion of ecosystem
      services into holistic management strategies improves management by better
      capturing the diversity of positive and negative human-natural interactions and
      making explicit the benefits to society. To facilitate this inclusion, we propose
      a conceptual model that merges the broadly applied Driver, Pressure, State,
      Impact, and Response (DPSIR) conceptual model with ecosystem services yielding a
      Driver, Pressure, State, Ecosystem service, and Response (EBM-DPSER) conceptual
      model. The impact module in traditional DPSIR models focuses attention upon
      negative anthropomorphic impacts on the ecosystem; by replacing impacts with
      ecosystem services the EBM-DPSER model incorporates not only negative, but also
      positive changes in the ecosystem. Responses occur as a result of changes in
      ecosystem services and include inter alia management actions directed at
      proactively altering human population or individual behavior and infrastructure
      to meet societal goals. The EBM-DPSER conceptual model was applied to the Florida
      Keys and Dry Tortugas marine ecosystem as a case study to illustrate how it can
      inform management decisions. This case study captures our system-level
      understanding and results in a more holistic representation of ecosystem and
      human society interactions, thus improving our ability to identify trade-offs.
      The EBM-DPSER model should be a useful operational tool for implementing EBM, in
      that it fully integrates our knowledge of all ecosystem components while focusing
      management attention upon those aspects of the ecosystem most important to human
      society and does so within a framework already familiar to resource managers. 

PMID- 23951003
TI  - Prevalence and risk factors of CKD in Chinese patients with periodontal disease.
AB  - BACKGROUND: Periodontal disease is common among adults and is associated with an
      increasing risk of chronic kidney disease (CKD). We aimed to investigate the
      prevalence and risk factors of CKD in patients with periodontal disease in China.
      METHODS: In the current cross-sectional study, patients with periodontal disease
      were included from Guangdong Provincial Stomatological Hospital between March
      2011 and August 2011. CKD was defined as estimated glomerular filtration rate
      (eGFR) <60 mL/min/1.73 m(2), the presence of albuminuria, or hematuria. All
      patients with periodontal disease underwent a periodontal examination, including
      periodontal probing pocket depth, gingival recession, and clinical attachment
      level by Florida Probe. They completed a questionnaire and had blood and urine
      samples taken. The adjusted prevalence of indicators of kidney damage was
      calculated and risk factors associated with CKD were analyzed. RESULTS: A total
      of 1392 patients with periodontal disease were invited to participate this study
      and 1268 completed the survey and examination. After adjusting for age and sex,
      the prevalence of reduced eGFR, albuminuria, and hematuria was 2.7% (95% CI 1.7
      3.7), 6.7% (95% CI 5.5-8.1) and 10.9% (95% CI 9.2-12.5), respectively. The
      adjusted prevalence of CKD was 18.2% (95% CI 16.2-20.3). Age, male, diabetes,
      hypertension, history of CKD, hyperuricemia, and interleukin-6 levels (>=7.54
      ng/L) were independent risk factors for reduced eGFR. Female, diabetes,
      hypertension, history of CKD, hyperuricemia, high level of cholesterol, and high
      sensitivity C-reactive protein (hsCRP) (>= 1.03 mg/L) and TNF-alpha levels (>=
      1.12 ng/L) were independently associated with an increased risk of albuminuria.
      Female, lower education (<high school), and history of CKD were independent risk
      factors for hematuria. CONCLUSIONS: 18.2% of Chinese patients with periodontal
      disease have proteinuria, hematuria, or reduced eGFR, indicating the presence of
      kidney damage. Whether prevention or treatment of periodontal disease can reduce
      the high prevalence of CKD, however, remains to be further investigated.

PMID- 23951004
TI  - Occult hepatitis B virus infection in anti-HBs-positive infants born to HBsAg
      positive mothers in China.
AB  - OBJECTIVE: To investigate the prevalence of occult HBV infection (OBI) among
      children and to characterize virology of occult HBV, we conducted an
      epidemiological survey. METHODS: 186 HB-vaccinated infants born to HBsAg-positive
      mothers were included in the study. Serological tests for HBV markers were
      performed using commercial ELISA kits. Real-time quantitative PCR and nested PCR
      were used to detect HBV DNA. PCR products of the C and pre-S/S regions were
      sequenced and analyzed. RESULTS: 1.61% (3/186) infants were HBsAg positive, and
      4.92% (9/183) infants were considered as occult infection. The viral load of
      mothers was associated with occult infection (P = 0.020). Incomplete three-dose
      injections of HB vaccine was associated with HBV infection (P = 0.022). Six OBI
      infants were positive for anti-HBs, but their titers were not greater than 100
      mIU/mL. Seven isolated HBV pre-S/S sequences were obtained from nine OBI infants.
      Three of the sequences were genotype C, and four of the sequences were genotype
      C/D. Escape mutation S143L was found in the four sequences of genotype C/D. All
      seven sequences lacked G145R and other escape mutation in S region. CONCLUSIONS:
      Occult HBV infection was detected in anti-HBs positive infants born to HBsAg
      positive mothers in China. Occult infection was associated with absent anti-HBs
      or with low anti-HBs level, high maternal viral loads and escape mutations in the
      S gene.

PMID- 23951005
TI  - Gadd153 and NF-kappaB crosstalk regulates 27-hydroxycholesterol-induced increase
      in BACE1 and beta-amyloid production in human neuroblastoma SH-SY5Y cells.
AB  - beta-amyloid (Abeta) peptide, accumulation of which is a culprit for Alzheimer's
      disease (AD), is derived from the initial cleavage of amyloid precursor protein
      by the aspartyl protease BACE1. Identification of cellular mechanisms that
      regulate BACE1 production is of high relevance to the search for potential
      disease-modifying therapies that inhibit BACE1 to reduce Abeta accumulation and
      AD progression. In the present study, we show that the cholesterol oxidation
      product 27-hydroxycholesterol (27-OHC) increases BACE1 and Abeta levels in human
      neuroblastoma SH-SY5Y cells. This increase in BACE1 involves a crosstalk between
      the two transcription factors NF-kappaB and the endoplasmic reticulum stress
      marker, the growth arrest and DNA damage induced gene-153 (gadd153, also called
      CHOP). We specifically show that 27-OHC induces a substantial increase in NF
      kappaB binding to the BACE1 promoter and subsequent increase in BACE1
      transcription and Abeta production. The NF-kappaB inhibitor, sc514, significantly
      attenuated the 27-OHC-induced increase in NF-kappaB-mediated BACE1 expression and
      Abeta genesis. We further show that the 27-OHC-induced NF-kappaB activation and
      increased NF-kappaB-mediated BACE1 expression is contingent on the increased
      activation of gadd153. Silencing gadd153 expression with siRNA alleviated the 27
      OHC-induced increase in NF-kappaB activation, NF-kappaB binding to the BACE1
      promoter, and subsequent increase in BACE1 transcription and Abeta production. We
      also show that increased levels of BACE1 in the triple transgenic mouse model for
      AD is preceded by gadd153 and NF-kappaB activation. In summary, our study
      demonstrates that gadd153 and NF-kappaB work in concert to regulate BACE1
      expression. Agents that inhibit gadd153 activation and subsequent interaction
      with NF-kappaB might be promising targets to reduce BACE1 and Abeta
      overproduction and may ultimately serve as disease-modifying treatments for AD. 

PMID- 23951006
TI  - The molecular basis of inactivation of metronidazole-resistant Helicobacter
      pylori using polyethyleneimine functionalized zinc oxide nanoparticles.
AB  - In view of the world wide prevalence of Helicobacter pylori infection, its
      potentially serious consequences, and the increasing emergence of antibiotic
      resistant H. pylori strains there is an urgent need for the development of
      alternative strategies to combat the infection. In this study it has been
      demonstrated that polyethyleneimine (PEI) functionalized zinc oxide (ZnO)
      nanoparticles (NPs) inhibit the growth of a metronidazole-resistant strain of H.
      pylori and the molecular basis of the anti-bacterial activity of ZnO-PEI NP has
      been investigated. The ZnO-PEI NP was synthesized using a wet chemical method
      with a core size of approximately 3-7 nm. Internalization and distribution of ZnO
      PEI NP without agglomeration was observed in H. pylori cytosol by electron
      microscopy. Several lines of evidence including scanning electron microscopy,
      propidium iodide uptake and ATP assay indicate severe membrane damage in ZnO-PEI
      NP treated H. pylori. Intracellular ROS generation increased rapidly following
      the treatment of H. pylori with ZnO-PEI NP and extensive degradation of 16S and
      23S rRNA was observed by quantitative reverse-transcriptase PCR. Finally,
      considerable synergy between ZnO-PEI NP and antibiotics was observed and it has
      been demonstrated that the concentration of ZnO-PEI NP (20 ug/ml) that is non
      toxic to human cells could be used in combination with sub-inhibitory
      concentrations of antibiotics for the inhibition of H. pylori growth. 

PMID- 23951007
TI  - Intestinal microbiota composition of interleukin-10 deficient C57BL/6J mice and
      susceptibility to Helicobacter hepaticus-induced colitis.
AB  - The mouse pathobiont Helicobacter hepaticus can induce typhlocolitis in
      interleukin-10-deficient mice, and H. hepaticus infection of immunodeficient mice
      is widely used as a model to study the role of pathogens and commensal bacteria
      in the pathogenesis of inflammatory bowel disease. C57BL/6J Il10(-/-) mice kept
      under specific pathogen-free conditions in two different facilities (MHH and
      MIT), displayed strong differences with respect to their susceptibilities to H.
      hepaticus-induced intestinal pathology. Mice at MIT developed robust
      typhlocolitis after infection with H. hepaticus, while mice at MHH developed no
      significant pathology after infection with the same H. hepaticus strain. We
      hypothesized that the intestinal microbiota might be responsible for these
      differences and therefore performed high resolution analysis of the intestinal
      microbiota composition in uninfected mice from the two facilities by deep
      sequencing of partial 16S rRNA amplicons. The microbiota composition differed
      markedly between mice from both facilities. Significant differences were also
      detected between two groups of MHH mice born in different years. Of the 119
      operational taxonomic units (OTUs) that occurred in at least half the cecum or
      colon samples of at least one mouse group, 24 were only found in MIT mice, and
      another 13 OTUs could only be found in MHH samples. While most of the MHH
      specific OTUs could only be identified to class or family level, the MIT-specific
      set contained OTUs identified to genus or species level, including the
      opportunistic pathogen, Bilophila wadsworthia. The susceptibility to H. hepaticus
      induced colitis differed considerably between Il10(-/-) mice originating from the
      two institutions. This was associated with significant differences in microbiota
      composition, highlighting the importance of characterizing the intestinal
      microbiome when studying murine models of IBD. 

PMID- 23951008
TI  - Gene expression profiles in relation to tension and dissociation in borderline
      personality disorder.
AB  - The biological underpinnings of borderline personality disorder (BPD) and its
      psychopathology including states of aversive tension and dissociation is poorly
      understood. Our goal was to examine transcriptional changes associated with
      states of tension or dissociation within individual patients in a pilot study.
      Dissociation is not only a critical symptom of BPD but has also been associated
      with higher risk for self-mutilation and depression. We conducted a whole blood
      gene expression profile analysis using quantitative PCR in 31 female inpatients
      with BPD. For each individual, two samples were drawn during a state of high
      tension and dissociation, while two samples were drawn at non-tension states.
      There was no association between gene expression and tension states. However, we
      could show that Interleukin-6 was positively correlated to dissociation scores,
      whereas Guanine nucleotide-binding protein G(s) subunit alpha isoforms, Mitogen
      activated protein kinase 3 and 8, Guanine nucleotide-binding protein G(i) subunit
      alpha-2, Beta-arrestin-1 and 2, and Cyclic AMP-responsive element-binding protein
      were negatively correlated to dissociation. Our data point to a potential
      association of dissociation levels with the expression of genes involved in
      immune system regulation as well as cellular signalling/second-messenger systems.
      Major limitations of the study are the the possibly heterogeneous cell
      proportions in whole blood and the heterogeneous medication. 

PMID- 23951009
TI  - Dynamics of forward and backward translocation of mRNA in the ribosome.
AB  - Translocation of the mRNA-tRNA complex in the ribosome, which is catalyzed by
      elongation factor EF-G, is one of critical steps in the elongation cycle of
      protein synthesis. Besides this conventional forward translocation, the backward
      translocation can also occur, which can be catalyzed by elongation factor LepA.
      However, the molecular mechanism of the translocation remains elusive. To
      understand the mechanism, here we study theoretically the dynamics of the forward
      translocation under various nucleotide states of EF-G and the backward
      translocation in the absence of and in the presence of LepA. We present a
      consistent explanation of spontaneous forward translocations in the absence of EF
      G, the EF-G-catalyzed forward translocations in the presence of a non
      hydrolysable GTP analogue and in the presence of GTP, and the spontaneous and
      LepA-catalyzed backward translocation. The theoretical results provide
      quantitative explanations of a lot of different, independent experimental data,
      and also provide testable predictions. 

PMID- 23951010
TI  - Control of cleft glutamate concentration and glutamate spill-out by perisynaptic
      glia: uptake and diffusion barriers.
AB  - Most glutamatergic synapses in the mammalian central nervous system are covered
      by thin astroglial processes that exert a dual action on synaptically released
      glutamate: they form physical barriers that oppose diffusion and they carry
      specific transporters that remove glutamate from the extracellular space. The
      present study was undertaken to investigate the dual action of glia by means of
      computer simulation. A realistic synapse model based on electron microscope data
      and Monte Carlo algorithms were used for this purpose. Results show (1) that
      physical obstacles formed by glial processes delay glutamate exit from the cleft
      and (2) that this effect is efficiently counteracted by glutamate uptake. Thus,
      depending on transporter densities, the presence of perisynaptic glia may result
      in increased or decreased glutamate transient in the synaptic cleft. Changes in
      temporal profiles of cleft glutamate concentration induced by glia differentially
      impact the response of the various synaptic and perisynaptic receptor subtypes.
      In particular, GluN2B- and GluN2C-NMDA receptor responses are strongly modified
      while GluN2A-NMDA receptor responses are almost unaffected. Thus, variations in
      glial transporter expression may allow differential tuning of NMDA receptors
      according to their subunit composition. In addition, simulation data suggest that
      the sink effect generated by transporters accumulation in the vicinity of the
      release site is the main mechanism limiting glutamate spill-out. Physical
      obstacles formed by glial processes play a comparatively minor role.

PMID- 23951011
TI  - Increased reticulocytosis during infancy is associated with increased
      hospitalizations in sickle cell anemia patients during the first three years of
      life.
AB  - OBJECTIVE: Among older children with sickle cell anemia, leukocyte counts,
      hemoglobin, and reticulocytosis have previously been suggested as disease
      severity markers. Here we explored whether these blood parameters may be useful
      to predict early childhood disease severity when tested in early infancy, defined
      as postnatal ages 60-180 days. STUDY DESIGN: Data from fifty-nine subjects who
      were followed at Children's National Medical Center's Sickle Cell Program for at
      least three years was retrospectively analyzed. Comparisons were made between
      white blood cell counts, hemoglobin and reticulocyte levels measured at ages 60
      180 days and the clinical course of sickle cell anemia during infancy and
      childhood. RESULTS: A majority of subjects had demonstrable anemia with increased
      reticulocytosis. Only increased absolute reticulocyte levels during early infancy
      were associated with a significant increase in hospitalization during the first
      three years of life. Higher absolute reticulocyte counts were also associated
      with a markedly shorter time to first hospitalizations and a four-fold higher
      cumulative frequency of clinical manifestations over the first three years of
      life. No significant increase in white blood cell counts was identified among the
      infant subjects. CONCLUSIONS: These data suggest that during early infancy,
      increased reticulocytosis among asymptomatic SCA subjects is associated with
      increased severity of disease in childhood.

PMID- 23951012
TI  - Trypsin potentiates human fibrocyte differentiation.
AB  - Trypsin-containing topical treatments can be used to speed wound healing,
      although the mechanism of action is unknown. To help form granulation tissue and
      heal wounds, monocytes leave the circulation, enter the wound tissue, and
      differentiate into fibroblast-like cells called fibrocytes. We find that 20 to
      200 ng/ml trypsin (concentrations similar to those used in wound dressings)
      potentiates the differentiation of human monocytes to fibrocytes in cell culture.
      Adding trypsin inhibitors increases the amount of trypsin needed to potentiate
      fibrocyte differentiation, suggesting that the potentiating effect is dependent
      on trypsin proteolytic activity. Proteases with other site specificities such as
      pepsin, endoprotease GluC, and chymotrypsin do not potentiate fibrocyte
      differentiation. This potentiation requires the presence of albumin in the
      culture medium, and tryptic fragments of human or bovine albumin also potentiate
      fibrocyte differentiation. These results suggest that topical trypsin speeds
      wound healing by generating tryptic fragments of albumin, which in turn
      potentiate fibrocyte differentiation. 

PMID- 23951013
TI  - The MRC1/CD68 ratio is positively associated with adipose tissue lipogenesis and
      with muscle mitochondrial gene expression in humans.
AB  - BACKGROUND: Alternative macrophages (M2) express the cluster differentiation (CD)
      206 (MCR1) at high levels. Decreased M2 in adipose tissue is known to be
      associated with obesity and inflammation-related metabolic disturbances. Here we
      aimed to investigate MCR1 relative to CD68 (total macrophages) gene expression in
      association with adipogenic and mitochondrial genes, which were measured in human
      visceral [VWAT, n = 147] and subcutaneous adipose tissue [SWAT, n = 76] and in
      rectus abdominis muscle (n = 23). The effects of surgery-induced weight loss were
      also longitudinally evaluated (n = 6). RESULTS: MCR1 and CD68 gene expression
      levels were similar in VWAT and SWAT. A higher proportion of CD206 relative to
      total CD68 was present in subjects with less body fat and lower fasting glucose
      concentrations. The ratio MCR1/CD68was positively associated with IRS1gene
      expression and with the expression of lipogenic genes such as ACACA, FASN and
      THRSP, even after adjusting for BMI. The ratio MCR1/CD68 in SWAT increased
      significantly after the surgery-induced weight loss (+44.7%; p = 0.005) in
      parallel to the expression of adipogenic genes. In addition, SWAT MCR1/CD68ratio
      was significantly associated with muscle mitochondrial gene expression (PPARGC1A,
      TFAM and MT-CO3). AT CD206 was confirmed by immunohistochemistry to be specific
      of macrophages, especially abundant in crown-like structures. CONCLUSION: A
      decreased ratio MCR1/CD68 is linked to adipose tissue and muscle mitochondrial
      dysfunction at least at the level of expression of adipogenic and mitochondrial
      genes.

PMID- 23951014
TI  - Loss of protein kinase C-delta protects against LPS-induced osteolysis owing to
      an intrinsic defect in osteoclastic bone resorption.
AB  - Bone remodeling is intrinsically regulated by cell signaling molecules. The
      Protein Kinase C (PKC) family of serine/threonine kinases is involved in multiple
      signaling pathways including cell proliferation, differentiation, apoptosis and
      osteoclast biology. However, the precise involvement of individual PKC isoforms
      in the regulation of osteoclast formation and bone homeostasis remains unclear.
      Here, we identify PKC-delta as the major PKC isoform expressed among all PKCs in
      osteoclasts; including classical PKCs (-alpha, -beta and -gamma), novel PKCs (
      delta, -epsilon, -eta and -theta) and atypical PKCs (-iota/lambda and -zeta).
      Interestingly, pharmacological inhibition and genetic ablation of PKC-delta
      impairs osteoclastic bone resorption in vitro. Moreover, disruption of PKC-delta
      activity protects against LPS-induced osteolysis in mice, with osteoclasts
      accumulating on the bone surface failing to resorb bone. Treatment with the PKC
      delta inhibitor Rottlerin, blocks LPS-induced bone resorption in mice.
      Consistently, PKC-delta deficient mice exhibit increased trabeculae bone
      containing residual cartilage matrix, indicative of an osteoclast-rich
      osteopetrosis phenotype. Cultured ex vivo osteoclasts derived from PKC-delta null
      mice exhibit decreased CTX-1 levels and MARKS phosphorylation, with enhanced
      formation rates. This is accompanied by elevated gene expression levels of
      cathepsin K and PKC -alpha, -gamma and -epsilon, as well as altered signaling of
      pERK and pcSrc416/527 upon RANKL-induction, possibly to compensate for the
      defects in bone resorption. Collectively, our data indicate that PKC-delta is an
      intrinsic regulator of osteoclast formation and bone resorption and thus is a
      potential therapeutic target for pathological osteolysis. 

PMID- 23951015
TI  - Protective efficacy of baculovirus dual expression system vaccine expressing
      Plasmodium falciparum circumsporozoite protein.
AB  - We have previously developed a new malaria vaccine delivery system based on the
      baculovirus dual expression system (BDES). In this system, expression of malaria
      antigens is driven by a dual promoter consisting of the baculovirus-derived
      polyhedrin and mammal-derived cytomegalovirus promoters. To test this system for
      its potential as a vaccine against human malaria parasites, we investigated
      immune responses against the newly developed BDES-based Plasmodium falciparum
      circumsporozoite protein vaccines (BDES-PfCSP) in mice and Rhesus monkeys.
      Immunization of mice with BDES-PfCSP induced Th1/Th2-mixed type immune responses
      with high PfCSP-specific antibody (Ab) titers, and provided significant
      protection against challenge from the bites of mosquitoes infected with a
      transgenic P. berghei line expressing PfCSP. Next, we evaluated the
      immunogenicity of the BDES-PfCSP vaccine in a rhesus monkey model. Immunization
      of BDES-PfCSP elicited high levels of anti-PfCSP Ab responses in individual
      monkeys. Moreover, the sera from the immunized monkeys remarkably blocked
      sporozoite invasion of HepG2 cells. Taken together with two animal models, our
      results indicate that this novel vaccine platform (BDES) has potential clinical
      application as a vaccine against malaria. 

PMID- 23951016
TI  - Long-term responses of the endemic reef-builder Cladocora caespitosa to
      Mediterranean warming.
AB  - Recurrent climate-induced mass-mortalities have been recorded in the
      Mediterranean Sea over the past 15 years. Cladocora caespitosa, the sole
      zooxanthellate scleractinian reef-builder in the Mediterranean, is among the
      organisms affected by these episodes. Extensive bioconstructions of this endemic
      coral are very rare at the present time and are threatened by several stressors.
      In this study, we assessed the long-term response of this temperate coral to
      warming sea-water in the Columbretes Islands (NW Mediterranean) and described,
      for the first time, the relationship between recurrent mortality events and local
      sea surface temperature (SST) regimes in the Mediterranean Sea. A water
      temperature series spanning more than 20 years showed a summer warming trend of
      0.06 degrees C per year and an increased frequency of positive thermal anomalies.
      Mortality resulted from tissue necrosis without massive zooxanthellae loss and
      during the 11-year study, necrosis was recorded during nine summers separated
      into two mortality periods (2003-2006 and 2008-2012). The highest necrosis rates
      were registered during the first mortality period, after the exceptionally hot
      summer of 2003. Although necrosis and temperature were significantly associated,
      the variability in necrosis rates during summers with similar thermal anomalies
      pointed to other acting factors. In this sense, our results showed that these
      differences were more closely related to the interannual temperature context and
      delayed thermal stress after extreme summers, rather than to acclimatisation and
      adaption processes. 

PMID- 23951017
TI  - Protein tyrosine phosphatase 1B deficiency ameliorates murine experimental
      colitis via the expansion of myeloid-derived suppressor cells.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a key molecule in modulating low
      degree inflammatory conditions such as diabetes. The role of PTP1B in other
      chronic inflammations, however, remains unknown. Here, we report that PTP1B
      deficiency ameliorates Dextran Sulfate Sodium (DSS)-induced murine experimental
      colitis via expanding CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs).
      Employing DSS-induced murine experimental colitis as inflammatory animal model,
      we found that, compared with wild-type littermates, PTP1B-null mice demonstrated
      greater resistance to DSS-induced colitis, as reflected by slower weight-loss,
      greater survival rates and decreased PMN and macrophage infiltration into the
      colon. The evidence collectively also demonstrated that the resistance of PTP1B
      null mice to DSS-induced colitis is based on the expansion of MDSCs. First, PTP1B
      null mice exhibited a greater frequency of MDSCs in the bone marrow (BM),
      peripheral blood and spleen when compared with wild-type littermates. Second,
      PTP1B levels in BM leukocytes were significantly decreased after cells were
      induced into MDSCs by IL-6 and GM-CSF, and the MDSC induction occurred more
      rapidly in PTP1B-null mice than in wild-type littermates, suggesting PTP1B as a
      negative regulator of MDSCs. Third, the adoptive transfer of MDSCs into mice with
      DSS-colitis significantly attenuated colitis, which accompanies with a decreased
      serum IL-17 level. Finally, PTP1B deficiency increased the frequency of MDSCs
      from BM cells likely through enhancing the activities of signal transducer and
      activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2). In conclusion,
      our study provides the first evidences that PTP1B deficiency ameliorates murine
      experimental colitis via expanding MDSCs. 

PMID- 23951018
TI  - Influence of vectors' risk-spreading strategies and environmental stochasticity
      on the epidemiology and evolution of vector-borne diseases: the example of
      Chagas' disease.
AB  - Insects are known to display strategies that spread the risk of encountering
      unfavorable conditions, thereby decreasing the extinction probability of genetic
      lineages in unpredictable environments. To what extent these strategies influence
      the epidemiology and evolution of vector-borne diseases in stochastic
      environments is largely unknown. In triatomines, the vectors of the parasite
      Trypanosoma cruzi, the etiological agent of Chagas' disease, juvenile development
      time varies between individuals and such variation most likely decreases the
      extinction risk of vector populations in stochastic environments. We developed a
      simplified multi-stage vector-borne SI epidemiological model to investigate how
      vector risk-spreading strategies and environmental stochasticity influence the
      prevalence and evolution of a parasite. This model is based on available
      knowledge on triatomine biodemography, but its conceptual outcomes apply, to a
      certain extent, to other vector-borne diseases. Model comparisons between
      deterministic and stochastic settings led to the conclusion that environmental
      stochasticity, vector risk-spreading strategies (in particular an increase in the
      length and variability of development time) and their interaction have drastic
      consequences on vector population dynamics, disease prevalence, and the relative
      short-term evolution of parasite virulence. Our work shows that stochastic
      environments and associated risk-spreading strategies can increase the prevalence
      of vector-borne diseases and favor the invasion of more virulent parasite strains
      on relatively short evolutionary timescales. This study raises new questions and
      challenges in a context of increasingly unpredictable environmental variations as
      a result of global climate change and human interventions such as habitat
      destruction or vector control. 

PMID- 23951019
TI  - The characteristic and changes of the event-related potentials (ERP) and brain
      topographic maps before and after treatment with rTMS in subjective tinnitus
      patients.
AB  - OBJECTIVES: To compare the event-related potentials (ERPs) and brain topographic
      maps characteristic and change in normal controls and subjective tinnitus
      patients before and after repetitive transcranial magnetic stimulation (rTMS)
      treatment. METHODS AND PARTICIPANTS: The ERPs and brain topographic maps elicited
      by target stimulus were compared before and after 1-week treatment with rTMS in
      20 subjective tinnitus patients and 16 healthy controls. RESULTS: Before rTMS,
      target stimulus elicited a larger N1 component than the standard stimuli
      (repeating sounds)in control group but not in tinnitus patients. Instead, the
      tinnitus group pre-treatment exhibited larger amplitude of N1 in response to
      standard stimuli than to deviant stimuli. Furthermore tinnitus patients had
      smaller mismatch negativity (MMN) and late discriminative negativity
      (LDN)component at Fz compared with the control group. After rTMS treatment,
      tinnitus patients showed increased N1 response to deviant stimuli and larger MMN
      and LDN compared with pre-treatment. The topographic maps for the tinnitus group
      before rTMS -treatment demonstrated global asymmetry between the left and right
      cerebral hemispheres with more negative activities in left side and more positive
      activities in right side. In contrast, the brain topographic maps for patients
      after rTMS-treatment and controls seem roughly symmetrical. The ERP amplitudes
      and brain topographic maps in post-treatment patient group showed no significant
      difference with those in controls. CONCLUSIONS: The characterical changes in ERP
      and brain topographic maps in tinnitus patients maybe related with the
      electrophysiological mechanism of tinnitus induction and development. It can be
      used as an objective biomarker for the evaluation of auditory central in
      subjective tinnitus patients. These findings support the notion that rTMS
      treatment in tinnitus patients may exert a beneficial effect.

PMID- 23951020
TI  - Comprehensive characterization of 10,571 mouse large intergenic noncoding RNAs
      from whole transcriptome sequencing.
AB  - Large intergenic noncoding RNAs (lincRNAs) have been recognized in recent years
      to constitute a significant portion of the mammalian transcriptome, yet their
      biological functions remain largely elusive. This is partly due to an incomplete
      annotation of tissue-specific lincRNAs in essential model organisms, particularly
      in mice, which has hindered the genetic annotation and functional
      characterization of these novel transcripts. In this report, we performed ab
      initio assembly of 1.9 billion tissue-specific RNA-sequencing reads across six
      tissue types, and identified 3,965 novel expressed lincRNAs in mice. Combining
      these with 6,606 documented lincRNAs, we established a comprehensive catalog of
      10,571 transcribed lincRNAs. We then systemically analyzed all mouse lincRNAs to
      reveal that some of them are evolutionally conserved and that they exhibit
      striking tissue-specific expression patterns. We also discovered that mouse
      lincRNAs carry unique genomic signatures, and that their expression level is
      correlated with that of neighboring protein-coding transcripts. Finally, we
      predicted that a large portion of tissue-specific lincRNAs are functionally
      associated with essential biological processes including the cell cycle and cell
      development, and that they could play a key role in regulating tissue development
      and functionality. Our analyses provide a framework for continued discovery and
      annotation of tissue-specific lincRNAs in model organisms, and our transcribed
      mouse lincRNA catalog will serve as a roadmap for functional analyses of lincRNAs
      in genetic mouse models. 

PMID- 23951021
TI  - Ratio of pro-resolving and pro-inflammatory lipid mediator precursors as
      potential markers for aggressive periodontitis.
AB  - Aggressive periodontitis (AgP) is a rapidly progressing type of periodontal
      disease in otherwise healthy individuals which causes destruction of the
      supporting tissues of the teeth. The disease is initiated by pathogenic bacteria
      in the dental biofilm, and the severity of inflammation and attachment loss
      varies with the host response. Recently, there has been an increased interest in
      determining the role of lipid mediators in inflammatory events and the concept of
      pro-inflammatory and pro-resolution lipid mediators has been brought into focus
      also in periodontal disease. The present study aimed to determine the profile of
      omega-3 or n3- as well as omega-6 or n6- polyunsaturated fatty acids (PUFAs) and
      PUFA-metabolites of linoleic acid, arachidonic acid (AA), eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA) in gingival crevicular fluid (GCF), saliva
      and serum in AgP patients and healthy controls. In total, 60 selected n3- and n6
      PUFAs and various PUFA metabolites were measured using high performance liquid
      chromatography-tandem electrospray ionisation mass spectrometry (HPLC-ESI-MS-MS).
      Of these, 51 could be quantified in this study. The concentrations of the
      majority were low in saliva samples compared with serum and GCF, but were mainly
      higher in AgP patients compared with healthy controls in all three kinds of
      sample. Ratios of n3- to n6-PUFAs (DHA + EPA)/AA were significantly lower in the
      GCF of AgP patients than in the healthy controls. Furthermore, various ratios of
      the direct precursors of the pro-resolution lipid mediators (precursors of
      resolvins and protectins) were calculated against the precursors of mainly pro
      inflammatory lipid mediators. These ratios were mainly lower in GCF and saliva of
      AgP patients, compared with healthy controls, but only reached significance in
      GCF (P<0.05). To conclude, the ratios of precursors of pro-resolution/pro
      inflammatory lipid mediators seem to be more relevant for describing the disease
      status of AgP than the concentration of specific lipid mediators. 

PMID- 23951022
TI  - Comparison of IHC, FISH and RT-PCR methods for detection of ALK rearrangements in
      312 non-small cell lung cancer patients in Taiwan.
AB  - BACKGROUND: Recently Echinoderm microtubule-associated protein-like 4- anaplastic
      lymphoma kinase (EML4-ALK) fusion gene has become an important biomarker for ALK
      tyrosine kinase inhibitor (crizotinib) treatment in NSCLC. However, the best
      detection method and the significance of EML4-ALK variant types remain uncertain.
      METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR), fluorescence
      in Situ hybridization (FISH) and Immunohistochemical (IHC) stain were performed
      on tumor tissues of 312 NSCLC patients for detection of ALK rearrangements.
      Mutation analyses for EGFR and KRAS genes were also performed. RESULTS: Thirteen
      of the 312 patients (4.17%) had ALK rearrangements detected by RT-PCR. If RT-PCR
      data was used as the gold standard, FISH tests had a low sensitivity (58.33%),
      but very good specificity (99.32%). IHC stain had better sensitivity (91.67%)
      than FISH, but lower specificity (79.52%), when the cut off was IHC2+. All of the
      8 patients with high abundance of EML4-ALK positive cells in tumor tissues
      (assessed by the signal intensities of the RT-PCR product), were also have high
      expression of ALK protein (IHC3+), and positive for FISH, except one failed in
      FISH. Variants 3a+3b (4/5, 80%) of EML4-ALK fusion gene were more common to have
      high abundance of EML4-ALK positive cells in tumor tissues than variant 1 (1/3,
      33.3%). Meta-analysis of the published data of 2273 NSCLC patients revealed that
      variant 3 (23/44, 52.3%) was the most common type in Chinese population, while
      variant 1 (28/37, 75.7%) was most common in Caucasian. CONCLUSIONS: Among the
      three detection methods, RT-PCR could detect not only the presence of EML4-ALK
      fusion gene and their variant types, but also the abundance of EML4-ALK positive
      cells in NSCLC tumor tissues. The latter two factors might affect the treatment
      response to anti-ALK inhibitor. Including RT-PCR as a diagnostic test for ALK
      inhibitor treatment in the prospective clinical trials is recommended.

PMID- 23951023
TI  - Effect of dielectric and liquid on plasma sterilization using dielectric barrier
      discharge plasma.
AB  - Plasma sterilization offers a faster, less toxic and versatile alternative to
      conventional sterilization methods. Using a relatively small, low temperature,
      atmospheric, dielectric barrier discharge surface plasma generator, we achieved
      >= 6 log reduction in concentration of vegetative bacterial and yeast cells
      within 4 minutes and >= 6 log reduction of Geobacillus stearothermophilus spores
      within 20 minutes. Plasma sterilization is influenced by a wide variety of
      factors. Two factors studied in this particular paper are the effect of using
      different dielectric substrates and the significance of the amount of liquid on
      the dielectric surface. Of the two dielectric substrates tested (FR4 and semi
      ceramic (SC)), it is noted that the FR4 is more efficient in terms of time taken
      for complete inactivation. FR4 is more efficient at generating plasma as shown by
      the intensity of spectral peaks, amount of ozone generated, the power used and
      the speed of killing vegetative cells. The surface temperature during plasma
      generation is also higher in the case of FR4. An inoculated FR4 or SC device
      produces less ozone than the respective clean devices. Temperature studies show
      that the surface temperatures reached during plasma generation are in the range
      of 30 degrees C-66  degrees C (for FR4) and 20  degrees C-49  degrees C (for SC).
      Surface temperatures during plasma generation of inoculated devices are lower
      than the corresponding temperatures of clean devices. pH studies indicate a
      slight reduction in pH value due to plasma generation, which implies that while
      temperature and acidification may play a minor role in DBD plasma sterilization,
      the presence of the liquid on the dielectric surface hampers sterilization and as
      the liquid evaporates, sterilization improves.

PMID- 23951024
TI  - Cannabinoid receptor CB2 modulates axon guidance.
AB  - Navigation of retinal projections towards their targets is regulated by guidance
      molecules and growth cone transduction mechanisms. Here, we present in vitro and
      in vivo evidences that the cannabinoid receptor 2 (CB2R) is expressed along the
      retino-thalamic pathway and exerts a modulatory action on axon guidance. These
      effects are specific to CB2R since no changes were observed in mice where the
      gene coding for this receptor was altered (cnr2 (-/-)). The CB2R induced
      morphological changes observed at the growth cone are PKA dependent and require
      the presence of the netrin-1 receptor, Deleted in Colorectal Cancer. Interfering
      with endogenous CB2R signalling using pharmacological agents increased retinal
      axon length and induced aberrant projections. Additionally, cnr2 (-/-) mice
      showed abnormal eye-specific segregation of retinal projections in the dorsal
      lateral geniculate nucleus (dLGN) indicating CB2R's implication in retinothalamic
      development. Overall, this study demonstrates that the contribution of
      endocannabinoids to brain development is not solely mediated by CB1R, but also
      involves CB2R. 

PMID- 23951025
TI  - Candidatus Syngnamydia venezia, a novel member of the phylum Chlamydiae from the
      broad nosed pipefish, Syngnathus typhle.
AB  - Chlamydia are obligate intracellular bacteria and important pathogens of humans
      and animals. Chlamydia-related bacteria are also major fish pathogens, infecting
      epithelial cells of the gills and skin to cause the disease epitheliocystis.
      Given the wide distribution, ancient origins and spectacular diversity of bony
      fishes, this group offers a rich resource for the identification and isolation of
      novel Chlamydia. The broad-nosed pipefish (Syngnathus typhle) is a widely
      distributed and genetically diverse temperate fish species, susceptible to
      epitheliocystis across much of its range. We describe here a new bacterial
      species, Candidatus Syngnamydia venezia; epitheliocystis agent of S. typhle and
      close relative to other chlamydial pathogens which are known to infect diverse
      hosts ranging from invertebrates to humans. 

PMID- 23951026
TI  - Discrimination and other barriers to accessing health care: perspectives of
      patients with mild and moderate intellectual disability and their carers.
AB  - BACKGROUND: People with intellectual disability have a higher prevalence of
      physical health problems but often experience disparities in accessing health
      care. In England, a number of legislative changes, policies and recommendations
      have been introduced to improve health care access for this population. The aim
      of this qualitative study was to examine the extent to which patients with
      intellectual disability and their carers experience discrimination or other
      barriers in accessing health services, and whether health care experiences have
      improved over the last decade years. METHOD AND MAIN FINDINGS: Twenty nine
      participants (14 patient and carer dyads, and one carer) took part in semi
      structured interviews. The interviews were audio-taped and transcribed and
      analysed using thematic analysis. Eight themes were identified. Half the
      participants thought that the patient had been treated unfairly or had been
      discriminated against by health services. There were accounts of negative staff
      attitudes and behaviour, and failure of services to make reasonable adjustments.
      Other barriers included problems with communication, and accessing services
      because of lack of knowledge of local services and service eligibility issues;
      lack of support and involvement of carers; and language problems in participants
      from minority ethnic groups. Most participants were able to report at least one
      example of good practice in health care provision. Suggestions for improving
      services are presented. CONCLUSION: Despite some improvements to services as a
      result of health policies and recommendations, more progress is required to
      ensure that health services make reasonable adjustments to reduce both direct and
      indirect discrimination of people with intellectual disability.

PMID- 23951027
TI  - Optogenetic control of PIP3: PIP3 is sufficient to induce the actin-based active
      part of growth cones and is regulated via endocytosis.
AB  - Phosphatidylinositol-3,4,5-trisphosphate (PIP3) is highly regulated in a
      spatiotemporal manner and plays multiple roles in individual cells. However, the
      local dynamics and primary functions of PIP3 in developing neurons remain unclear
      because of a lack of techniques for manipulating PIP3 spatiotemporally. We
      addressed this issue by combining optogenetic control and observation of
      endogenous PIP3 signaling. Endogenous PIP3 was abundant in actin-rich structures
      such as growth cones and "waves", and PIP3-rich plasma membranes moved actively
      within growth cones. To study the role of PIP3 in developing neurons, we
      developed a PI3K photoswitch that can induce production of PIP3 at specific
      locations upon blue light exposure. We succeeded in producing PIP3 locally in
      mouse hippocampal neurons. Local PIP3 elevation at neurite tips did not induce
      neurite elongation, but it was sufficient to induce the formation of filopodia
      and lamellipodia. Interestingly, ectopic PIP3 elevation alone activated membranes
      to form actin-based structures whose behavior was similar to that of growth-cone
      like "waves". We also found that endocytosis regulates effective PIP3
      concentration at plasma membranes. These results revealed the local dynamics and
      primary functions of PIP3, providing fundamental information about PIP3 signaling
      in neurons. 

PMID- 23951028
TI  - IL-1alpha expression in pancreatic ductal adenocarcinoma affects the tumor cell
      migration and is regulated by the p38MAPK signaling pathway.
AB  - The interplay between the tumor cells and the surrounding stroma creates
      inflammation, which promotes tumor growth and spread. The inflammation is a
      hallmark for pancreatic adenocarcinoma (PDAC) and is to high extent driven by IL
      1alpha. IL-1alpha is expressed and secreted by the tumor cells and exerting its
      effect on the stroma, i.e. cancer associated fibroblasts (CAF), which in turn
      produce massive amount of inflammatory and immune regulatory factors. IL-1
      induces activation of transcription factors such as nuclear factor-kappabeta (NF
      kappabeta), but also activator protein 1 (AP-1) via the small G-protein Ras.
      Dysregulation of Ras pathways are common in cancer as this oncogene is the most
      frequently mutated in many cancers. In contrast, the signaling events leading up
      to the expression of IL-1alpha by tumor cells are not well elucidated. Our aim
      was to examine the signaling cascade involved in the induction of IL-1alpha
      expression in PDAC. We found p38MAPK, activated by the K-Ras signaling pathway,
      to be involved in the expression of IL-1alpha by PDAC as blocking this pathway
      decreased both the gene and protein expression of IL-1alpha. Blockage of the
      P38MAPK signaling in PDAC also dampened the ability of the tumor cell to induce
      inflammation in CAFs. In addition, the IL-1alpha autocrine signaling regulated
      the migratory capacity of PDAC cells. Taken together, the blockage of signaling
      pathways leading to IL-1alpha expression and/or neutralization of IL-1alpha in
      the PDAC microenvironment should be taken into consideration as possible
      treatment or complement to existing treatment of this cancer. 

PMID- 23951029
TI  - Disparities in oral cancer survival among mentally ill patients.
AB  - BACKGROUND: Many studies have reported excess cancer mortality in patients with
      mental illness. However, scant studies evaluated the differences in cancer
      treatment and its impact on survival rates among mentally ill patients. Oral
      cancer is one of the ten most common cancers in the world. We investigated
      differences in treatment type and survival rates between oral cancer patients
      with mental illness and without mental illness. METHODS: Using the National
      Health Insurance (NHI) database, we compared the type of treatment and survival
      rates in 16687 oral cancer patients from 2002 to 2006. The utilization rate of
      surgery for oral cancer was compared between patients with mental illness and
      without mental illness using logistic regression. The Cox proportional hazards
      model was used for survival analysis. RESULTS: Oral cancer patients with mental
      disorder conferred a grave prognosis, compared with patients without mental
      illness (hazard ratios [HR] = 1.58; 95% confidence interval [CI] = 1.30-1.93;
      P<0.001). After adjusting for patients' characteristics and hospital
      characteristics, patients with mental illness were less likely to receive surgery
      with or without adjuvant therapy (odds ratio [OR] = 0.47; 95% CI = 0.34-0.65;
      P<0.001). In multivariate analysis, oral cancer patients with mental illness
      carried a 1.58-times risk of death (95% CI = 1.30-1.93; P<0.001). CONCLUSIONS:
      Oral cancer patients with mental illness were less likely to undergo surgery with
      or without adjuvant therapy than those without mental illness. Patients with
      mental illness have a poor prognosis compared to those without mental illness. To
      reduce disparities in physical health, public health strategies and welfare
      policies must continue to focus on this vulnerable group.

PMID- 23951030
TI  - Prevalence, awareness, medication, control, and risk factors associated with
      hypertension in Bai ethnic group in rural China: the Yunnan Minority Eye Study.
AB  - PURPOSE: This study aimed to assess the prevalence, awareness, treatment, and
      control of hypertension and their associated factors among Bai ethnic population
      in the rural China. METHODS: A population-based survey was conducted in 2010 with
      a randomly cluster sampling in rural communities in Dali, southwest China. A
      total of 2133 adults aged 50 or above were interviewed, and their blood pressure,
      height, weight and waist circumference were measured. Hypertension was defined as
      a mean SBP>=140 mmHg and/or DBP>=90 mmHg, and/or current use of antihypertensive
      medications. RESULTS: The prevalence of hypertension was 42.1% (899/2133), and
      the age- and gender-adjusted prevalence was 40.0%. Among the hypertensive
      participants, 28.4% (255/899)were aware of their condition, while 24.6% (221/899)
      took antihypertensive medications, with only 7.5% (67/899) of those achieving
      blood pressure control (<140/90 mmHg). Risk factors for hypertension were older
      age, smoking, alcohol drinking, family history of HBP, overweight, and obesity,
      while protective factors included being lean, and having finished senior high
      school or above. CONCLUSIONS: Hypertension prevalence is high among the
      population of Bai ethnic group in China, while the associated risk factors of
      hypertension include overweight/obesity, cigarette smoking, history of
      hypertension, and older age. The percentages of hypertensive participants aware
      of their hypertension and those taking antihypertensive medications were low with
      an incredibly low proportion of hypertensive patients who kept their hypertension
      under control. It is suggested that health education and hypertension screening
      programs be carried out in the area for the high blood pressure prevention and
      control.

PMID- 23951031
TI  - Comparison of various anthropometric and body fat indices in identifying
      cardiometabolic disturbances in Chinese men and women.
AB  - BACKGROUND: Although many adiposity indices may be used to predict obesity
      related health risks, uncertainty remains over which of them performs best.
      OBJECTIVE: This study compared the predictive capability of direct and indirect
      adiposity measures in identifying people at higher risk of metabolic
      abnormalities. METHODS: This population-based cross-sectional study recruited
      2780 women and 1160 men. Body weight and height, waist circumference (WC), and
      hip circumference (HC) were measured and body mass index (BMI), waist-to-hip
      ratio (WHR), and waist-to-height ratio (WHtR) were calculated. Body fat (and
      percentage of fat) over the whole body and the trunk were determined by
      bioelectrical impedance analysis (BIA). Blood pressure, fasting lipid profiles,
      and glucose and urine acid levels were assessed. RESULTS: In women, the ROC and
      the multivariate logistic regression analyses both showed that WHtR consistently
      had the best performance in identifying hypertension, dyslipidemia,
      hyperuricemia, diabetes/IFG, and metabolic syndrome (MetS). In men, the ROC
      analysis showed that WHtR was the best predictor of hypertension, WHtR and WC
      were equally good predictors of dyslipidemia and MetS, and WHtR was the second
      best predictor of hyperuricemia and diabetes/IFG. The multivariate logistic
      regression also found WHtR to be superior in discriminating between MetS,
      diabetes/IFG, and dyslipidemia while BMI performed better in predicting
      hypertension and hyperuricemia in men. The BIA-derived indices were the second
      worst predictors for all of the endpoints, and HC was the worst. CONCLUSION: WHtR
      was the best predictor of various metabolic abnormalities. BMI may be used as an
      alternative measure of obesity for identifying hypertension in both sexes.

PMID- 23951032
TI  - Expired CO2 levels indicate degree of lung aeration at birth.
AB  - As neonatal resuscitation critically depends upon lung aeration at birth,
      knowledge of the progression of this process is required to guide ongoing care.
      We investigated whether expired CO2 (ECO2) levels indicate the degree of lung
      aeration immediately after birth in two animal models and in preterm infants.
      Lambs were delivered by caesarean section and ventilated from birth. In lambs,
      ECO2 levels were significantly (p<0.0001) related to tidal volumes and CO2
      clearance/breath increased exponentially when tidal volumes were greater than 6
      mL/kg. Preterm (28 days of gestation; term = 32 days) rabbits were also delivered
      by caesarean section and lung aeration was measured using phase contrast X-ray
      imaging. In rabbit kittens, ECO2 levels were closely related (p<0.001) to lung
      volumes at end-inflation and were first detected when ~7% of the distal lung
      regions were aerated. ECO2 levels in preterm infants at birth also correlated
      with tidal volumes. In each infant, ECO2 levels increased to >10 mmHg 28 (median)
      (21-36) seconds before the heart rate increased above 100 beats per minute. These
      data demonstrate that ECO2 levels can indicate the relative degree of lung
      aeration after birth and can be used to clinically assess ventilation in the
      immediate newborn period. 

PMID- 23951033
TI  - Periodontal disease and risk of preeclampsia: a meta-analysis of observational
      studies.
AB  - BACKGROUND: Many epidemiological studies have found a positive association
      between periodontal disease (PD) and the risk of preeclampsia, but the magnitude
      of this association varies and independent studies have reported conflicting
      findings. We performed a meta-analysis to ascertain the relationship between PD
      and preeclampsia. METHODS: The PubMed database was searched up to January 12,
      2013, for relevant observational studies on an association between PD and the
      risk of preeclampsia. Data were extracted and analyzed independently by two
      authors. The meta-analysis was performed using comprehensive meta-analysis
      software. RESULTS: Thirteen observational case-control studies and two cohort
      studies, involving 1089 preeclampsia patients, were identified. Based on a random
      effects meta-analysis, a significant association between PD and preeclampsia was
      identified (odds ratio = 2.79, 95% confidence interval CI, 2.01-3.01, P<0.0001).
      CONCLUSIONS: Although the causality remains unclear, the association between PD
      and preeclampsia may reflect the induction of PD by the preeclamptic state, or it
      may be part of an overall exaggerated inflammatory response to pregnancy. Larger
      randomized controlled trials with preeclampsia as the primary outcome and
      pathophysiological studies are required to explore causality and to dissect the
      biological mechanisms involved.

PMID- 23951034
TI  - Genome-wide association study identifies a novel canine glaucoma locus.
AB  - Glaucoma is an optic neuropathy and one of the leading causes of blindness. Its
      hereditary forms are classified into primary closed-angle (PCAG), primary open
      angle (POAG) and primary congenital glaucoma (PCG). Although many loci have been
      mapped in human, only a few genes have been identified that are associated with
      the development of glaucoma and the genetic basis of the disease remains poorly
      understood. Glaucoma has also been described in many dog breeds, including Dandie
      Dinmont Terriers (DDT) in which it is a late-onset (>7 years) disease. We
      designed clinical and genetic studies to better define the clinical features of
      glaucoma in the DDT and to identify the genetic cause. Clinical diagnosis was
      based on ophthalmic examinations of the affected dogs and 18 additionally
      investigated unaffected DDTs. We collected DNA from over 400 DTTs and a genome
      wide association study was performed in a cohort of 23 affected and 23 controls,
      followed by a fine mapping, a replication study and candidate gene sequencing.
      The clinical study suggested that ocular abnormalities including abnormal
      iridocorneal angles and pectinate ligament dysplasia are common (50% and 72%,
      respectively) in the breed and the disease resembles human PCAG. The genetic
      study identified a novel 9.5 Mb locus on canine chromosome 8 including the 1.6 Mb
      best associated region (p = 1.63 * 10(-10), OR = 32 for homozygosity). Mutation
      screening in five candidate genes did not reveal any causative variants. This
      study indicates that although ocular abnormalities are common in DDTs, the
      genetic risk for glaucoma is conferred by a novel locus on CFA8. The canine locus
      shares synteny to a region in human chromosome 14q, which harbors several loci
      associated with POAG and PCG. Our study reveals a new locus for canine glaucoma
      and ongoing molecular studies will likely help to understand the genetic etiology
      of the disease.

PMID- 23951035
TI  - Neutral and acidic oligosaccharides supplementation does not increase the vaccine
      antibody response in preterm infants in a randomized clinical trial.
AB  - BACKGROUND: In preterm infants, a decreased immunological response and lower
      serological effectiveness are observed after immunizations due to ineffectiveness
      of both humoral and cellular immune mechanisms. OBJECTIVE: To determine the
      effect of 80% neutral oligosaccharides [small-chain galacto-oligosaccharides/long
      chain fructo-oligosaccharides (scGOS/lcFOS)] in combination with 20% pectin
      derived acidic oligosaccharides (pAOS) on antibody concentrations after DTaP-IPV
      Hib immunization in preterm infants. DESIGN: In this randomized clinical trial,
      preterm infants with gestational age <32 weeks and/or birth weight <1500 g
      received enteral supplementation with scGOS/lcFOS/pAOS or placebo (maltodextrin)
      between days 3 and 30 of life. Blood samples were collected at 5 and 12 months of
      age. RESULTS: In total, 113 infants were included. Baseline and nutritional
      characteristics were not different in both groups. Geometric mean titers were not
      different after prebiotic supplementation at 5 months, Ptx (37/44 EU/ml), FHA
      (78/96 EU/ml), Prn (78/80 EU/ml), Diphtheria (0.40/0.57 IU/ml), Tetanus
      (0.74/0.99 IU/ml) and Hib (0.35/0.63 ug/ml), and at 12 months Ptx (55/66 EU/ml),
      FHA (122/119 EU/ml), Prn (116/106 Eu/ml), Diphtheria (0.88/1.11 IU/ml), Tetanus
      (1.64/1.79 IU/ml) and Hib (2.91/2.55 ug/ml). CONCLUSIONS: Enteral supplementation
      of neutral (scGOS/lcFOS) and acidic oligosaccharides (pAOS) does not improve the
      immunization response in preterm infants. TRIAL REGISTRATION: Controlled
      Trials.com ISRCTN16211826 ISRCTN16211826.

PMID- 23951037
TI  - Mapping global diversity patterns for migratory birds.
AB  - Nearly one in five bird species has separate breeding and overwintering
      distributions, and the regular migrations of these species cause a substantial
      seasonal redistribution of avian diversity across the world. However, despite its
      ecological importance, bird migration has been largely ignored in studies of
      global avian biodiversity, with few studies having addressed it from a
      macroecological perspective. Here, we analyse a dataset on the global
      distribution of the world's birds in order to examine global spatial patterns in
      the diversity of migratory species, including: the seasonal variation in overall
      species diversity due to migration; the contribution of migratory birds to local
      bird diversity; and the distribution of narrow-range and threatened migratory
      birds. Our analyses reveal a striking asymmetry between the Northern and Southern
      hemispheres, evident in all of the patterns investigated. The highest migratory
      bird diversity was found in the Northern Hemisphere, with high inter-continental
      turnover in species composition between breeding and non-breeding seasons, and
      extensive regions (at high latitudes) where migratory birds constitute the
      majority of the local avifauna. Threatened migratory birds are concentrated
      mainly in Central and Southern Asia, whereas narrow-range migratory species are
      mainly found in Central America, the Himalayas and Patagonia. Overall, global
      patterns in the diversity of migratory birds indicate that bird migration is
      mainly a Northern Hemisphere phenomenon. The asymmetry between the Northern and
      Southern hemispheres could not have easily been predicted from the combined
      results of regional scale studies, highlighting the importance of a global
      perspective. 

PMID- 23951036
TI  - Lung cancer cells that survive ionizing radiation show increased integrin
      alpha2beta1- and EGFR-dependent invasiveness.
AB  - Ionizing radiation (IR)-enhanced tumor invasiveness is emerging as a contributor
      to the limited benefit of radiotherapy; however, its mechanism is still unclear.
      We previously showed that subcloned lung adenocarcinoma A549 cells (P cells),
      which survived 10 Gy IR (IR cells), acquired high invasiveness in vitro. Here, we
      tried to identify the mechanism by which IR cells increase their invasiveness by
      examining altered gene expression and signaling pathways in IR cells compared
      with those in P cells. To simulate the microenvironment in vivo, cells were
      embedded in a three-dimensional (3D) collagen type I gel, in which the IR cells
      were elongated, while the P cells were spherical. The integrin expression pattern
      was surveyed, and expression levels of the integrin alpha2 and beta1 subunits
      were significantly elevated in IR cells. Knockdown of alpha2 expression or
      functional blockade of integrin alpha2beta1 resulted in a round morphology of IR
      cells, and abrogated their invasion in the collagen matrix, suggesting the
      molecule's essential role in cell spread and invasion in 3D collagen. Epidermal
      growth factor receptor (EGFR) also presented enhanced expression and activation
      in IR cells. Treatment with EGFR tyrosine kinase inhibitor, PD168393, decreased
      the ratio of elongated cells and cell invasiveness. Signaling molecules,
      including extracellular signal-regulated kinase-1/2 (Erk1/2) and Akt, exhibited
      higher activation in IR cells. Inhibition of Akt activation by treating with
      phosphoinositide 3-kinase (PI3K) inhibitor LY294002 decreased IR cell invasion,
      whereas inhibition of Erk1/2 activation by mitogen-activated protein kinase
      kinase (MEK) inhibitor U0126 did not. Our results show that integrin alpha2beta1
      and EGFR cooperatively promote higher invasiveness of IR-survived lung cancer
      cells, mediated in part by the PI3K/Akt signaling pathway, and might serve as
      alternative targets in combination with radiotherapy. 

PMID- 23951038
TI  - Time- and cost-efficient identification of T-DNA insertion sites through targeted
      genomic sequencing.
AB  - Forward genetic screens enable the unbiased identification of genes involved in
      biological processes. In Arabidopsis, several mutant collections are publicly
      available, which greatly facilitates such practice. Most of these collections
      were generated by agrotransformation of a T-DNA at random sites in the plant
      genome. However, precise mapping of T-DNA insertion sites in mutants isolated
      from such screens is a laborious and time-consuming task. Here we report a
      simple, low-cost and time efficient approach to precisely map T-DNA insertions
      simultaneously in many different mutants. By combining sequence capture, next
      generation sequencing and 2D-PCR pooling, we developed a new method that allowed
      the rapid localization of T-DNA insertion sites in 55 out of 64 mutant plants
      isolated in a screen for gyrase inhibition hypersensitivity. 

PMID- 23951039
TI  - Overexpression of IRM1 enhances resistance to aphids in Arabidopsis thaliana.
AB  - Aphids are insects that cause direct damage to crops by the removal of phloem
      sap, but more importantly they spread devastating viruses. Aphids use their
      sophisticated mouthpart (i.e. stylet) to feed from the phloem sieve elements of
      the host plant. To identify genes that affect host plant resistance to aphids, we
      previously screened an Arabidopsis thaliana activation tag mutant collection. In
      such mutants, tagged genes are overexpressed by a strong 35S enhancer adjacent to
      the natural promoter, resulting in a dominant gain-of-function phenotype. We
      previously identified several of these mutants on which the aphid Myzus persicae
      showed a reduced population development compared with wild type. In the present
      study we show that the gene responsible for the phenotype of one of the mutants
      is At5g65040 and named this gene Increased Resistance to Myzus persicae 1 (IRM1).
      Overexpression of the cloned IRM1 gene conferred a phenotype identical to that of
      the original mutant. Conversely, an IRM1 knockout mutant promoted aphid
      population development compared to the wild type. We performed Electrical
      Penetration Graph analysis to investigate how probing and feeding behaviour of
      aphids was affected on plants that either overexpressed IRM1 or contained a
      knockout mutation in this gene. The EPG results indicated that the aphids
      encounter resistance factors while reaching for the phloem on the overexpressing
      line. This resistance mechanism also affected other aphid species and is
      suggested to be of mechanical nature. Interestingly, genetic variation for IRM1
      expression in response to aphid attack was observed. Upon aphid attack the
      expression of IRM1 was initially (after 6 hours) induced in ecotype Wassilewskija
      followed by suppression. In Columbia-0, IRM1 expression was already suppressed
      six hours after the start of the infestation. The resistance conferred by the
      overexpression of IRM1 in A. thaliana trades off with plant growth. 

PMID- 23951041
TI  - Fossil worm burrows reveal very early terrestrial animal activity and shed light
      on trophic resources after the end-cretaceous mass extinction.
AB  - The widespread mass extinctions at the end of the Cretaceous caused world-wide
      disruption of ecosystems, and faunal responses to the one-two punch of severe
      environmental perturbation and ecosystem collapse are still unclear. Here we
      report the discovery of in situ terrestrial fossil burrows from just above the
      impact-defined Cretaceous-Paleogene (K/Pg) boundary in southwestern North Dakota.
      The crisscrossing networks of horizontal burrows occur at the interface of a
      lignitic coal and silty sandstone, and reveal intense faunal activity within
      centimeters of the boundary clay. Estimated rates of sedimentation and coal
      formation suggest that the burrows were made less than ten thousand years after
      the end-Cretaceous impact. The burrow characteristics are most consistent with
      burrows of extant earthworms. Moreover, the burrowing and detritivorous habits of
      these annelids fit models that predict the trophic and sheltering lifestyles of
      terrestrial animals that survived the K/Pg extinction event. In turn, such
      detritus-eaters would have played a critical role in supporting secondary
      consumers. Thus, some of the carnivorous vertebrates that radiated after the K/Pg
      extinction may owe their evolutionary success to thriving populations of
      earthworms. 

PMID- 23951040
TI  - Preschool children's behavioral tendency toward social indirect reciprocity.
AB  - Social indirect reciprocity seems to be crucial in enabling large-scale
      cooperative networks among genetically unrelated individuals in humans. However,
      there are relatively few studies on social indirect reciprocity in children
      compared to adults. Investigating whether young children have a behavioral
      tendency toward social indirect reciprocity will help us understand how and when
      the fundamental ability to form cooperative relationships among adults is
      acquired. Using naturalistic observation at a nursery school, this study examined
      whether 5- to 6-year-olds show a behavioral tendency to engage in social indirect
      reciprocity in response to their peers' prosocial behavior toward a third party.
      The results revealed that bystander children tended to display prosocial behavior
      toward their peers more frequently after observing these peers' prosocial
      behavior toward third-party peers, compared with control situations; this
      suggests that 5- to 6-year-olds may have an essential behavioral tendency to
      establish social indirect reciprocity when interacting with peers in their daily
      lives. In addition, bystanders tended to display affiliative behavior after
      observing focal children's prosocial behavior. In other words, observing peers'
      prosocial behavior toward third-party peers evoked bystanders' positive emotions
      toward the helpers. Considering both the present results and previous findings,
      we speculate that in preschoolers, such positive emotions might mediate the
      increase in the bystander's prosocial behavior toward the helper. In addition, an
      intuitional emotional process plays an important role in the preschooler's
      behavioral tendency toward social indirect reciprocity in natural interactions
      with peers. 

PMID- 23951043
TI  - Phase transitions in paradigm shift models.
AB  - Two general models for paradigm shifts, deterministic propagation model (DM) and
      stochastic propagation model (SM), are proposed to describe paradigm shifts and
      the adoption of new technological levels. By defining the order parameter m based
      on the diversity of ideas, Delta, it is studied when and how the phase transition
      or the disappearance of a dominant paradigm occurs as a cost C in DM or an
      innovation probability alpha in SM increases. In addition, we also investigate
      how the propagation processes affect the transition nature. From analytical
      calculations and numerical simulations m is shown to satisfy the scaling relation
      m=1-f(C/N) for DM with the number of agents N. In contrast, m in SM scales as m=1
      f(alpha(a)N).

PMID- 23951042
TI  - Cathepsin K is present in invasive oral tongue squamous cell carcinoma in vivo
      and in vitro.
AB  - OBJECTIVES: Cathepsin K, a lysosomal cysteine protease, is expressed in the tumor
      microenvironment (TME) of skin carcinoma, but nothing is known about cathepsin K
      in oral tongue squamous cell carcinoma (OTSCC). Our aim was to describe the
      expression of cathepsin K in invasive OTSCC in vitro and in a series of clinical
      cancer specimens. MATERIALS AND METHODS: OTSCC invasion in vitro was studied
      using invasive HSC-3 tongue carcinoma cells in 3D organotypic models. In total,
      121 mobile tongue OTSCCs and 10 lymph node metastases were analyzed for cathepsin
      K expression. The association between cathepsin K expression and
      clinicopathological factors was evaluated. RESULTS: Cysteine protease inhibitor
      E64 and cathepsin K silencing significantly (p<0.0001) reduced HSC-3 cell
      invasion in the 3D models. Cathepsin K was expressed in a majority of carcinoma
      and metastatic cells, but the expression pattern in carcinoma cells did not
      correlate with clinical parameters. Instead, the weak expression of cathepsin K
      in the invasive TME front correlated with increased overall recurrence (p<0.05),
      and in early-stage tumors this pattern predicted both cancer recurrence and
      cancer-specific mortality (p<0.05 and p<0.005, respectively). CONCLUSIONS:
      Cathepsin K is expressed in OTSCC tissue in both carcinoma and TME cells.
      Although the diminished activity and expression in aggressive tongue HSC-3 cells
      reduced 3D invasion in vitro, the amount of cathepsin K in carcinoma cells was
      not associated with the outcome of cancer patients. Instead, cathepsin K in the
      invasive TME front seems to have a protective role in the complex progression of
      tongue cancer.

PMID- 23951044
TI  - Calpastatin gene (CAST) is not associated with late onset sporadic Parkinson's
      disease in the Han Chinese population.
AB  - Recent studies point to an association between the late-onset sporadic
      Parkinson's disease (PD) and single nucleotide polymorphisms (SNPs) rs1559085 and
      rs27852 in Ca(2+)-dependent protease calpain inhibitor calpastatin (CAST) gene.
      This finding is of interest since loss of CAST activity could result in over
      activated calpain, potentially leading to Ca(2+) dysregulation and loss of
      substantia nigra neurons in PD. We explored the association between CAST SNPs and
      late-onset sporadic PD in the Han Chinese population. The study included 615
      evaluable patients (363 male, 252 female) with PD and 636 neurologically healthy
      controls (380 male, 256 female) matched for age, gender, ethnicity, and area of
      residence. PD cases were identified from the PD cohort of the Chinese National
      Consortium on Neurodegenerative Diseases (www.chinapd.cn). A total of 24 tag-SNPs
      were genotyped capturing 95% of the genetic variation across the CAST gene. There
      was no association found between any of the polymorphisms and PD in all models
      tested (co-dominant, dominant-effect and recessive-effect). Similarly, none of
      the common haplotypes was associated with a risk for PD. Our data do not support
      a significant association between the CAST gene polymorphisms and late onset
      sporadic PD in the Han Chinese population. 

PMID- 23951045
TI  - The tip of the tail needle affects the rate of DNA delivery by bacteriophage P22.
AB  - The P22-like bacteriophages have short tails. Their virions bind to their
      polysaccharide receptors through six trimeric tailspike proteins that surround
      the tail tip. These short tails also have a trimeric needle protein that extends
      beyond the tailspikes from the center of the tail tip, in a position that
      suggests that it should make first contact with the host's outer membrane during
      the infection process. The base of the needle serves as a plug that keeps the DNA
      in the virion, but role of the needle during adsorption and DNA injection is not
      well understood. Among the P22-like phages are needle types with two completely
      different C-terminal distal tip domains. In the phage Sf6-type needle, unlike the
      other P22-type needle, the distal tip folds into a "knob" with a TNF-like fold,
      similar to the fiber knobs of bacteriophage PRD1 and Adenovirus. The phage HS1
      knob is very similar to that of Sf6, and we report here its crystal structure
      which, like the Sf6 knob, contains three bound L-glutamate molecules. A chimeric
      P22 phage with a tail needle that contains the HS1 terminal knob efficiently
      infects the P22 host, Salmonella enterica, suggesting the knob does not confer
      host specificity. Likewise, mutations that should abrogate the binding of L
      glutamate to the needle do not appear to affect virion function, but several
      different other genetic changes to the tip of the needle slow down potassium
      release from the host during infection. These findings suggest that the needle
      plays a role in phage P22 DNA delivery by controlling the kinetics of DNA
      ejection into the host. 

PMID- 23951046
TI  - Eprobe mediated real-time PCR monitoring and melting curve analysis.
AB  - Real-time monitoring of PCR is one of the most important methods for DNA and RNA
      detection widely used in research and medical diagnostics. Here we describe a new
      approach for combined real-time PCR monitoring and melting curve analysis using a
      3' end-blocked Exciton-Controlled Hybridization-sensitive fluorescent
      Oligonucleotide (ECHO) called Eprobe. Eprobes contain two dye moieties attached
      to the same nucleotide and their fluorescent signal is strongly suppressed as
      single-stranded oligonucleotides by an excitonic interaction between the dyes.
      Upon hybridization to a complementary DNA strand, the dyes are separated and
      intercalate into the double-strand leading to strong fluorescence signals.
      Intercalation of dyes can further stabilize the DNA/DNA hybrid and increase the
      melting temperature compared to standard DNA oligonucleotides. Eprobes allow for
      specific real-time monitoring of amplification reactions by hybridizing to the
      amplicon in a sequence-dependent manner. Similarly, Eprobes allow for analysis of
      reaction products by melting curve analysis. The function of different Eprobes
      was studied using the L858R mutation in the human epidermal growth factor
      receptor (EGFR) gene, and multiplex detection was demonstrated for the human EGFR
      and KRAS genes using Eprobes with two different dyes. Combining amplification and
      melting curve analysis in a single-tube reaction provides powerful means for new
      mutation detection assays. Functioning as "sequence-specific dyes", Eprobes hold
      great promises for future applications not only in PCR but also as hybridization
      probes in other applications. 

PMID- 23951047
TI  - Glycemic index, glycemic load and mammographic breast density: the EPIC Florence
      longitudinal study.
AB  - A few studies have evaluated the association between diet and mammographic breast
      density (MBD) and results are inconsistent. MBD, a well-recognized risk factor
      for breast cancer, has been proposed as a marker of cumulative exposure to
      hormones and growth factors. Diets with a high glycemic index (GI) or glycemic
      load (GL) may increase breast cancer risk, via an effect on the insulin-like
      growth factor axis. We have investigated the association between carbohydrate
      intake, GI, GL and MBD in a prospective study. We identified a large series of
      women, in the frame of the EPIC-Florence cohort, with a mammogram taken five
      years after enrolment, when detailed information on dietary and lifestyle habits
      and anthropometric measurements had been collected. Mammograms have been
      retrieved (1,668, 83%) and MBD assessed according to Wolfe's classification. We
      compared women with high MBD (P2+DY Wolfe's categories) with those with low MBD
      (N1+P1) through logistic models adjusted for age, education, body mass index,
      menopause, number of children, breast feeding, physical activity, non-alcohol
      energy, fibers, saturated fat and alcohol. A direct association between GL and
      high MBD emerged in the highest quintile of intake in comparison with the lowest
      quintile (OR = 1.73, 95%CI 1.13-2.67, p for trend = 0.048) while no association
      with glycemic index was evident. These results were confirmed after exclusion of
      women reporting to be on a diet or affected with diabetes, and when Hormone
      Replacement Therapy at the date of mammographic examination used to assess MBD
      was considered. The effect was particularly evident among leaner women, although
      no interaction was found. A positive association was suggested for increasing
      simple sugar and total carbohydrates intakes limited to the highest quintiles. In
      this Italian population we observed an association between glycemic load, total
      and rapidly absorbed carbohydrates and high MBD. These novel results warrant
      further investigations.

PMID- 23951048
TI  - Chronic alcohol-induced microRNA-155 contributes to neuroinflammation in a TLR4
      dependent manner in mice.
AB  - INTRODUCTION: Alcohol-induced neuroinflammation is mediated by pro-inflammatory
      cytokines and chemokines including tumor necrosis factor-alpha (TNFalpha),
      monocyte chemotactic protein-1 (MCP1) and interleukin-1-beta (IL-1beta). Toll
      like receptor-4 (TLR4) pathway induced nuclear factor-kappaB (NF-kappaB)
      activation is involved in the pathogenesis of alcohol-induced neuroinflammation.
      Inflammation is a highly regulated process. Recent studies suggest that microRNAs
      (miRNAs) play crucial role in fine tuning gene expression and miR-155 is a major
      regulator of inflammation in immune cells after TLR stimulation. AIM: To evaluate
      the role of miR-155 in the pathogenesis of alcohol-induced neuroinflammation.
      METHODS: Wild type (WT), miR-155- and TLR4-knockout (KO) mice received 5% ethanol
      containing or isocaloric control diet for 5 weeks. Microglia markers were
      measured by q-RTPCR; inflammasome activation was measured by enzyme activity;
      TNFalpha, MCP1, IL-1beta mRNA and protein were measured by q-RTPCR and ELISA;
      phospho-p65 protein and NF-kappaB were measured by Western-blotting and EMSA;
      miRNAs were measured by q-PCR in the cerebellum. MiR-155 was measured in
      immortalized and primary mouse microglia after lipopolysaccharide and ethanol
      stimulation. RESULTS: Chronic ethanol feeding up-regulated miR-155 and miR-132
      expression in mouse cerebellum. Deficiency in miR-155 protected mice from alcohol
      induced increase in inflammatory cytokines; TNFalpha, MCP1 protein and TNFalpha,
      MCP1, pro-IL-1beta and pro-caspase-1 mRNA levels were reduced in miR-155 KO
      alcohol-fed mice. NF-kappaB was activated in WT but not in miR-155 KO alcohol-fed
      mice. However increases in cerebellar caspase-1 activity and IL-1beta levels were
      similar in alcohol-fed miR-155-KO and WT mice. Alcohol-fed TLR4-KO mice were
      protected from the induction of miR-155. NF-kappaB activation measured by
      phosphorylation of p65 and neuroinflammation were reduced in alcohol-fed TLR4-KO
      compared to control mice. TLR4 stimulation with lipopolysaccharide in primary or
      immortalized mouse microglia resulted in increased miR-155. CONCLUSION: Chronic
      alcohol induces miR-155 in the cerebellum in a TLR4-dependent manner. Alcohol
      induced miR-155 regulates TNFalpha and MCP1 expression but not caspase-dependent
      IL-1beta increase in neuroinflammation.

PMID- 23951049
TI  - Novel dicarboxylate selectivity in an insect glutamate transporter homolog.
AB  - Mammals express seven transporters from the SLC1 (solute carrier 1) gene family,
      including five acidic amino acid transporters (EAAT1-5) and two neutral amino
      acid transporters (ASCT1-2). In contrast, insects of the order Diptera possess
      only two SLC1 genes. In this work we show that in the mosquito Culex
      quinquefasciatus, a carrier of West Nile virus, one of its two SLC1 EAAT-like
      genes encodes a transporter that displays an unusual selectivity for dicarboxylic
      acids over acidic amino acids. In eukaryotes, dicarboxylic acid uptake has been
      previously thought to be mediated exclusively by transporters outside the SLC1
      family. The dicarboxylate selectivity was found to be associated with two
      residues in transmembrane domain 8, near the presumed substrate binding site.
      These residues appear to be conserved in all eukaryotic SLC1 transporters (Asp444
      and Thr448, human EAAT3 numbering) with the exception of this novel C.
      quinquefasciatus transporter and an ortholog from the yellow fever mosquito Aedes
      aegypti, in which they are changed to Asn and Ala. In the prokaryotic EAAT-like
      SLC1 transporter DctA, a dicarboxylate transporter which was lost in the lineage
      leading to eukaryotes, the corresponding TMD8 residues are Ser and Ala.
      Functional analysis of engineered mutant mosquito and human transporters
      expressed in Xenopus laevis oocytes provide support for a model defining
      interactions of charged and polar transporter residues in TMD8 with alpha-amino
      acids and ions. Together with the phylogenetic evidence, the functional data
      suggest that a novel route of dicarboxylic acid uptake evolved in these mosquitos
      by mutations in an ancestral glutamate transporter gene. 

PMID- 23951050
TI  - Evolutionary drivers of diversification and distribution of a southern temperate
      stream fish assemblage: testing the role of historical isolation and spatial
      range expansion.
AB  - This study used phylogenetic analyses of mitochondrial cytochrome b sequences to
      investigate genetic diversity within three broadly co-distributed freshwater fish
      genera (Galaxias, Pseudobarbus and Sandelia) to shed some light on the processes
      that promoted lineage diversification and shaped geographical distribution
      patterns. A total of 205 sequences of Galaxias, 177 sequences of Pseudobarbus and
      98 sequences of Sandelia from 146 localities across nine river systems in the
      south-western Cape Floristic Region (South Africa) were used. The data were
      analysed using phylogenetic and haplotype network methods and divergence times
      for the clades retrieved were estimated using *BEAST. Nine extremely divergent
      (3.5-25.3%) lineages were found within Galaxias. Similarly, deep phylogeographic
      divergence was evident within Pseudobarbus, with four markedly distinct (3.8
      10.0%) phylogroups identified. Sandelia had two deeply divergent (5.5-5.9%)
      lineages, but seven minor lineages with strong geographical congruence were also
      identified. The Miocene-Pliocene major sea-level transgression and the resultant
      isolation of populations in upland refugia appear to have driven widespread
      allopatric divergence within the three genera. Subsequent coalescence of rivers
      during the Pleistocene major sea-level regression as well as intermittent
      drainage connections during wet periods are proposed to have facilitated range
      expansion of lineages that currently occur across isolated river systems. The
      high degree of genetic differentiation recovered from the present and previous
      studies suggest that freshwater fish diversity within the south-western CFR may
      be vastly underestimated, and taxonomic revisions are required. 

PMID- 23951051
TI  - Epithelial V-like antigen mediates efficacy of anti-alpha4 integrin treatment in
      a mouse model of multiple sclerosis.
AB  - Natalizumab inhibits the transmigration of activated T lymphocytes into the brain
      and is highly efficacious in multiple sclerosis (MS). However, from a
      pharmacogenomic perspective, its efficacy and safety in specific patients remain
      unclear. Here our goal was to analyze the effects of epithelial V-like antigen
      (EVA) on anti-alpha4 integrin (VLA4) efficacy in a mouse model of MS,
      experimental autoimmune encephalomyelitis (EAE). EVA has been previously
      characterized in human CD4 T lymphocytes, mouse thymic development, and choroid
      plexus epithelial cells. Further analysis here demonstrated expression in B
      lymphocytes and an increase in EVA+ lymphocytes following immunization. Following
      active induction of EAE using the MOG35-55 active immunization model, EVA
      deficient mice developed more severe EAE and white matter tissue injury as
      compared to wild type controls. This severe EAE phenotype did not respond to anti
      VLA4 treatment. In both the control antibody and anti-VLA4 conditions, these mice
      demonstrated persistent CNS invasion of mature B lymphocyte (CD19+, CD21+,
      sIgG+), increased serum autoantibody levels, and extensive complement and IgG
      deposition within lesions containing CD5+IgG+ cells. Wild type mice treated with
      control antibody also demonstrated the presence of CD19+, CD21+, sIgG+ cells
      within the CNS during peak EAE disease severity and detectable serum
      autoantibody. In contrast, wild type mice treated with anti-VLA4 demonstrated
      reduced serum autoantibody levels as compared to wild type controls and EVA
      knockout mice. As expected, anti-VLA4 treatment in wild type mice reduced the
      total numbers of all CNS mononuclear cells and markedly decreased CD4 T
      lymphocyte invasion. Treatment also reduced the frequency of CD19+, CD21+, sIgG+
      cells in the CNS. These results suggest that anti-VLA4 treatment may reduce B
      lymphocyte associated autoimmunity in some individuals and that EVA expression is
      necessary for an optimal therapeutic response. We postulate that these findings
      could optimize the selection of treatment responders.

PMID- 23951052
TI  - Candidate markers that associate with chemotherapy resistance in breast cancer
      through the study on Taxotere-induced damage to tumor microenvironment and gene
      expression profiling of carcinoma-associated fibroblasts (CAFs).
AB  - Recently, emerging evidence has suggested that carcinoma-associated fibroblasts
      (CAFs) could contribute to chemotherapy resistances in breast cancer treatment.
      The aim of this study is to compare the gene expression profiling of CAFs before
      and after chemotherapy and pick up candidate genes that might associate with
      chemotherapy resistance and could be used as predictors of treatment response.
      CAFs were cultured from surgically resected primary breast cancers and identified
      with immunohistochemistry (IHC) and Flow cytometry (FCM). MDA-MB-231 cells were
      cultured as the breast cancer cell line. Cell adhesion assay, invasion assay, and
      proliferation assay (MTT) were performed to compare the function of MDA-MB-231
      cells co-cultured with CAFs and MDA-MB-231 cells without co-culture, after
      chemotherapy. Totally 6 pairs of CAFs were prepared for microarray analysis. Each
      pair of CAFs were obtained from the same patient and classified into two groups.
      One group was treated with Taxotere (regarded as after chemotherapy) while the
      other group was not processed with Taxotere (regarded as before chemotherapy).
      According to our study, the primary-cultured CAFs exhibited characteristic
      phenotype. After chemotherapy, MDA-MB-231 cells co-cultured with CAFs displayed
      increasing adhesion, invasiveness and proliferation abilities, compared with MDA
      MB-231 cells without CAFs. Moreover, 35 differentially expressed genes (absolute
      fold change >2) were identified between CAFs after chemotherapy and before
      chemotherapy, including 17 up-regulated genes and 18 down-regulated genes. CXCL2,
      MMP1, IL8, RARRES1, FGF1, and CXCR7 were picked up as the candidate markers, of
      which the differential expression in CAFs before and after chemotherapy was
      confirmed. The results indicate the changes of gene expression in CAFs induced by
      Taxotere treatment and propose the candidate markers that possibly associate with
      chemotherapy resistance in breast cancer. 

PMID- 23951053
TI  - Cadherin-11 regulates motility in normal cortical neural precursors and
      glioblastoma.
AB  - Metastasizing tumor cells undergo a transformation that resembles a process in
      normal development when non-migratory epithelial cells modulate the expression of
      cytoskeletal and adhesion proteins to promote cell motility. Here we find a
      mesenchymal cadherin, Cadherin-11 (CDH11), is increased in cells exiting the
      ventricular zone (VZ) neuroepithelium during normal cerebral cortical
      development. When overexpressed in cortical progenitors in vivo, CDH11 causes
      premature exit from the neuroepithelium and increased cell migration. CDH11
      expression is elevated in human brain tumors, correlating with higher tumor grade
      and decreased patient survival. In glioblastoma, CDH11-expressing tumor cells can
      be found localized near tumor vasculature. Endothelial cells stimulate TGFbeta
      signaling and CDH11 expression in glioblastoma cells. TGFbeta promotes
      glioblastoma cell motility, and knockdown of CDH11 expression in primary human
      glioblastoma cells inhibits TGFbeta-stimulated migration. Together, these
      findings show that Cadherin-11 can promote cell migration in neural precursors
      and glioblastoma cells and suggest that endothelial cells increase tumor
      aggressiveness by co-opting mechanisms that regulate normal neural development. 

PMID- 23951054
TI  - The interaction of polymorphisms of IL10 and DBH was associated with general
      symptoms of PANSS with TD in Chinese Han schizophrenic patients.
AB  - OBJECTIVE: Tardive dyskinesia (TD) is a human hyperkinetic movement disorder as a
      result of potentially irreversible long-term chronic first-generation
      antipsychotic medications. Unfortunately, mechanisms involved in the development
      of TD have been poorly understood. Previous studies have indicated that some
      genetic polymorphisms of immune system and dopamine beta-hydroxylase (DBH) genes
      may be involved in the pathogenesis of TD. Rs1800872 and rs72393728 are located
      on the promoter of interleukin-10 (IL10) and DBH gene, respectively. The genetic
      association between the rs1800872 and TD is unclear. Previous studies have
      indicated that genetic variations of IL 10 and DBH are implicated in the positive
      and negative symptoms in schizophrenia. However, the interaction of two
      variations with severity of TD and symptoms of schizophrenic patients with TD has
      not been reported. The present study investigated whether these variations and
      their interaction were associated with clinical phenotypes of TD with
      schizophrenia in a genetically homogeneous northern Chinese Han population.
      METHODS: Rs1800872 and rs72393728 were genotyped in schizophrenic patients with
      TD (n = 372) and without TD (NTD; n = 412). The Abnormal Involuntary Movement
      Scale (AIMS) and Positive and Negative Syndrome Scale (PANSS) were applied to
      assess the severity of TD and psychopathology of schizophrenia, respectively.
      RESULTS: The allele and genotype frequencies of rs1800872 and rs72393728 did not
      significantly differ between TD and NTD patients (p>0.05). No significant
      difference was found in the AIMS total score among the genotypes of two loci
      (p>0.05). Interestingly, the interaction of rs1800872 and rs72393728 showed a
      significant association with the PANSS general score (p = 0.011), and a trend
      toward to the PANSS total score (p = 0.055). CONCLUSION: These findings suggest
      that the interaction of rs1800872 and rs72393728 variants may play a role in
      psychopathology of the general symptoms on PANSS in schizophrenic patients with
      TD in a northern Chinese Han population.

PMID- 23951056
TI  - Taxonomic, spatial and temporal patterns of bleaching in anemones inhabited by
      anemonefishes.
AB  - BACKGROUND: Rising sea temperatures are causing significant destruction to coral
      reef ecosystems due to coral mortality from thermally-induced bleaching (loss of
      symbiotic algae and/or their photosynthetic pigments). Although bleaching has
      been intensively studied in corals, little is known about the causes and
      consequences of bleaching in other tropical symbiotic organisms.
      METHODOLOGY/PRINCIPAL FINDINGS: This study used underwater visual surveys to
      investigate bleaching in the 10 species of anemones that host anemonefishes.
      Bleaching was confirmed in seven anemone species (with anecdotal reports of
      bleaching in the other three species) at 10 of 19 survey locations spanning the
      Indo-Pacific and Red Sea, indicating that anemone bleaching is taxonomically and
      geographically widespread. In total, bleaching was observed in 490 of the 13,896
      surveyed anemones (3.5%); however, this percentage was much higher (19-100%)
      during five major bleaching events that were associated with periods of elevated
      water temperatures and coral bleaching. There was considerable spatial variation
      in anemone bleaching during most of these events, suggesting that certain sites
      and deeper waters might act as refuges. Susceptibility to bleaching varied
      between species, and in some species, bleaching caused reductions in size and
      abundance. CONCLUSIONS/SIGNIFICANCE: Anemones are long-lived with low natural
      mortality, which makes them particularly vulnerable to predicted increases in
      severity and frequency of bleaching events. Population viability will be severely
      compromised if anemones and their symbionts cannot acclimate or adapt to rising
      sea temperatures. Anemone bleaching also has negative effects to other species,
      particularly those that have an obligate relationship with anemones. These
      effects include reductions in abundance and reproductive output of anemonefishes.
      Therefore, the future of these iconic and commercially valuable coral reef fishes
      is inextricably linked to the ability of host anemones to cope with rising sea
      temperatures associated with climate change.

PMID- 23951055
TI  - Aurora B but not rho/MLCK signaling is required for localization of
      diphosphorylated myosin II regulatory light chain to the midzone in cytokinesis.
AB  - Non-muscle myosin II is stimulated by monophosphorylation of its regulatory light
      chain (MRLC) at Ser19 (1P-MRLC). MRLC diphosphorylation at Thr18/Ser19 (2P-MRLC)
      further enhances the ATPase activity of myosin II. Phosphorylated MRLCs localize
      to the contractile ring and regulate cytokinesis as subunits of activated myosin
      II. Recently, we reported that 2P-MRLC, but not 1P-MRLC, localizes to the midzone
      independently of myosin II heavy chain during cytokinesis in cultured mammalian
      cells. However, the mechanism underlying the distinct localization of 1P- and 2P
      MRLC during cytokinesis is unknown. Here, we showed that depletion of the Rho
      signaling proteins MKLP1, MgcRacGAP, or ECT2 inhibited the localization of 1P
      MRLC to the contractile ring but not the localization of 2P-MRLC to the midzone.
      In contrast, depleting or inhibiting a midzone-localizing kinase, Aurora B,
      perturbed the localization of 2P-MRLC to the midzone but not the localization of
      1P-MRLC to the contractile ring. We did not observe any change in the
      localization of phosphorylated MRLC in myosin light-chain kinase (MLCK)-inhibited
      cells. Furrow regression was observed in Aurora B- and 2P-MRLC-inhibited cells
      but not in 1P-MRLC-perturbed dividing cells. Furthermore, Aurora B bound to 2P
      MRLC in vitro and in vivo. These results suggest that Aurora B, but not Rho/MLCK
      signaling, is essential for the localization of 2P-MRLC to the midzone in
      dividing HeLa cells. 

PMID- 23951057
TI  - Major depression is not associated with blunting of aversive responses; evidence
      for enhanced anxious anticipation.
AB  - According to the emotion-context insensitivity (ECI) hypothesis, major depressive
      disorder (MDD) is associated with a diminished ability to react emotionally to
      positive stimuli and with blunting of defensive responses to threat. That
      defensive responses are blunted in MDD seems inconsistent with the
      conceptualization and diagnostic nosology of MDD. The present study tested the
      ECI hypothesis in MDD using a threat of shock paradigm. Twenty-eight patients
      with MDD (35.5+/-10.4 years) were compared with 28 controls (35.1+/-7.4 years).
      Participants were exposed to three conditions: no shock, predictable shock, and
      unpredictable shock. Startle magnitude was used to assess defensive responses.
      Inconsistent with the ECI hypothesis, startle potentiation to predictable and
      unpredictable shock was not reduced in the MDD group. Rather, MDD patients showed
      elevated startle throughout testing as well as increased contextual anxiety
      during the placement of the shock electrodes and in the predictable condition. A
      regression analysis indicated that illness duration and Beck depression inventory
      scores explained 37% (p<.005) of the variance in patients' startle reactivity.
      MDD is not associated with emotional blunting but rather enhanced defensive
      reactivity during anticipation of harm. These results do not support a strong
      version of the ECI hypothesis. Understanding the nature of stimuli or situations
      that lead to blunted or enhanced defensive reactivity will provide better insight
      into dysfunctional emotional experience in MDD. 

PMID- 23951058
TI  - Impaired macrophage and satellite cell infiltration occurs in a muscle-specific
      fashion following injury in diabetic skeletal muscle.
AB  - BACKGROUND: Systemic elevations in PAI-1 suppress the fibrinolytic pathway
      leading to poor collagen remodelling and delayed regeneration of tibialis
      anterior (TA) muscles in type-1 diabetic Akita mice. However, how impaired
      collagen remodelling was specifically attenuating regeneration in Akita mice
      remained unknown. Furthermore, given intrinsic differences between muscle groups,
      it was unclear if the reparative responses between muscle groups were different.
      PRINCIPAL FINDINGS: Here we reveal that diabetic Akita muscles display
      differential regenerative responses with the TA and gastrocnemius muscles
      exhibiting reduced regenerating myofiber area compared to wild-type mice, while
      soleus muscles displayed no difference between animal groups following injury.
      Collagen levels in TA and gastrocnemius, but not soleus, were significantly
      increased post-injury versus controls. At 5 days post-injury, when
      degenerating/necrotic regions were present in both animal groups, Akita TA and
      gastrocnemius muscles displayed reduced macrophage and satellite cell
      infiltration and poor myofiber formation. By 10 days post-injury, necrotic
      regions were absent in wild-type TA but persisted in Akita TA. In contrast, Akita
      soleus exhibited no impairment in any of these measures compared to wild-type
      soleus. In an effort to define how impaired collagen turnover was attenuating
      regeneration in Akita TA, a PAI-1 inhibitor (PAI-039) was orally administered to
      Akita mice following cardiotoxin injury. PAI-039 administration promoted
      macrophage and satellite cell infiltration into necrotic areas of the TA and
      gastrocnemius. Importantly, soleus muscles exhibit the highest inducible
      expression of MMP-9 following injury, providing a mechanism for normative
      collagen degradation and injury recovery in this muscle despite systemically
      elevated PAI-1. CONCLUSIONS: Our findings suggest the mechanism underlying how
      impaired collagen remodelling in type-1 diabetes results in delayed regeneration
      is an impairment in macrophage infiltration and satellite cell recruitment to
      degenerating areas; a phenomena that occurs differentially between muscle groups.

PMID- 23951059
TI  - Force-controlled balance perturbations associated with falls in older people: a
      prospective cohort study.
AB  - Balance recovery from an unpredictable postural perturbation can be a challenging
      task for many older people and poor recovery could contribute to their risk of
      falls. This study examined associations between responses to unpredictable
      perturbations and fall risk in older people. 242 older adults (80.0 +/- 4.4
      years) underwent assessments of stepping responses to multi-directional force
      controlled waist-pull perturbations. Participants returned monthly falls
      calendars for the subsequent 12 months. Future falls were associated with lower
      force thresholds for stepping in the posterior and lateral but not anterior
      directions. Those with lower posterior force thresholds for stepping were 68%
      more likely to fall at home than those with higher force thresholds for stepping.
      These results suggest that amount of force that can be withstood following an
      unpredictable balance perturbation predicts future falls in community-dwelling
      older adults. Perturbations in the posterior direction best discriminated between
      future fallers and non-fallers.

PMID- 23951060
TI  - MicroRNA-185 and 342 inhibit tumorigenicity and induce apoptosis through blockade
      of the SREBP metabolic pathway in prostate cancer cells.
AB  - MicroRNA (miRNA or miR) inhibition of oncogenic related pathways has been shown
      to be a promising therapeutic approach for cancer. Aberrant lipid and cholesterol
      metabolism is involved in prostate cancer development and progression to end
      stage disease. We recently demonstrated that a key transcription factor for
      lipogenesis, sterol regulatory element-binding protein-1 (SREBP-1), induced fatty
      acid and lipid accumulation and androgen receptor (AR) transcriptional activity,
      and also promoted prostate cancer cell growth and castration resistance. SREBP-1
      was overexpressed in human prostate cancer and castration-resistant patient
      specimens. These experimental and clinical results indicate that SREBP-1 is a
      potential oncogenic transcription factor in prostate cancer. In this study, we
      identified two miRNAs, miR-185 and 342, that control lipogenesis and
      cholesterogenesis in prostate cancer cells by inhibiting SREBP-1 and 2 expression
      and down-regulating their targeted genes, including fatty acid synthase (FASN)
      and 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR). Both miR-185 and 342
      inhibited tumorigenicity, cell growth, migration and invasion in prostate cancer
      cell culture and xenograft models coincident with their blockade of lipogenesis
      and cholesterogenesis. Intrinsic miR-185 and 342 expression was significantly
      decreased in prostate cancer cells compared to non-cancerous epithelial cells.
      Restoration of miR-185 and 342 led to caspase-dependent apoptotic death in
      prostate cancer cells. The newly identified miRNAs, miR-185 and 342, represent a
      novel targeting mechanism for prostate cancer therapy. 

PMID- 23951061
TI  - Zileuton improves memory deficits, amyloid and tau pathology in a mouse model of
      Alzheimer's disease with plaques and tangles.
AB  - The 5-lipoxygenase (5LO) enzyme is widely distributed within the central nervous
      system. Previous works showed that this protein is up-regulated in Alzheimer's
      disease (AD), and plays an active role in the development of brain amyloidosis in
      the APP transgenic mice. In the present paper, we studied the effect of its
      pharmacological inhibition on the entire AD-like phenotype of a mouse model with
      plaques and tangles, the 3 * Tg mice. Compared with mice receiving placebo, the
      group treated with zileuton, a specific 5LO inhibitor, manifested a significant
      improvement of their memory impairments. The same animals had a significant
      reduction in Abeta levels and deposition, which was secondary to a down
      regulation of the gamma-secretase pathway. Additionally, while total tau levels
      were unchanged for both groups, zileuton-treated mice had a significant reduction
      in its phosphorylation state and insoluble forms, secondary to a decreased
      activation of the cdk5 kinase. These data establish a functional role for 5LO in
      the pathogenesis of the full spectrum of the AD-like phenotype and represent the
      successful completion of the initial step for the preclinical development of 5LO
      inhibitors as viable therapeutic agents for AD.

PMID- 23951062
TI  - Integrated genotypic analysis of hedgehog-related genes identifies subgroups of
      keratocystic odontogenic tumor with distinct clinicopathological features.
AB  - Keratocystic odontogenic tumor (KCOT) arises as part of Gorlin syndrome (GS) or
      as a sporadic lesion. Gene mutations and loss of heterozygosity (LOH) of the
      hedgehog receptor PTCH1 plays an essential role in the pathogenesis of KCOT.
      However, some KCOT cases lack evidence for gene alteration of PTCH1, suggesting
      that other genes in the hedgehog pathway may be affected. PTCH2 and SUFU
      participate in the occurrence of GS-associated tumors, but their roles in KCOT
      development are unknown. To elucidate the roles of these genes, we enrolled 36
      KCOT patients in a study to sequence their entire coding regions of PTCH1, PTCH2
      and SUFU. LOH and immunohistochemical expression of these genes, as well as the
      downstream targets of hedgehog signaling, were examined using surgically-excised
      KCOT tissues. PTCH1 mutations, including four novel ones, were found in 9
      hereditary KCOT patients, but not in sporadic KCOT patients. A pathogenic
      mutation of PTCH2 or SUFU was not found in any patients. LOH at PTCH1 and SUFU
      loci correlated with the presence of epithelial budding. KCOT harboring a
      germline mutation (Type 1) showed nuclear localization of GLI2 and frequent
      histological findings such as budding and epithelial islands, as well as the
      highest recurrence rate. KCOT with LOH but without a germline mutation (Type 2)
      less frequently showed these histological features, and the recurrence rate was
      lower. KCOT with neither germline mutation nor LOH (Type 3) consisted of two
      subgroups, Type 3A and 3B, which were characterized by nuclear and cytoplasmic
      GLI2 localization, respectively. Type 3B rarely exhibited budding and recurrence,
      behaving as the most amicable entity. The expression patterns of CCND1 and BCL2
      tended to correlate with these subgroups. Our data indicates a significant role
      of PTCH1 and SUFU in the pathogenesis of KCOT, and the genotype-oriented
      subgroups constitute entities with different potential aggressiveness. 

PMID- 23951063
TI  - Evaluation of reference genes for RT qPCR analyses of structure-specific and
      hormone regulated gene expression in Physcomitrella patens gametophytes.
AB  - The use of the moss Physcomitrella patens as a model system to study plant
      development and physiology is rapidly expanding. The strategic position of P.
      patens within the green lineage between algae and vascular plants, the high
      efficiency with which transgenes are incorporated by homologous recombination,
      advantages associated with the haploid gametophyte representing the dominant
      phase of the P. patens life cycle, the simple structure of protonemata, leafy
      shoots and rhizoids that constitute the haploid gametophyte, as well as a readily
      accessible high-quality genome sequence make this moss a very attractive
      experimental system. The investigation of the genetic and hormonal control of P.
      patens development heavily depends on the analysis of gene expression patterns by
      real time quantitative PCR (RT qPCR). This technique requires well characterized
      sets of reference genes, which display minimal expression level variations under
      all analyzed conditions, for data normalization. Sets of suitable reference genes
      have been described for most widely used model systems including e.g. Arabidopsis
      thaliana, but not for P. patens. Here, we present a RT qPCR based comparison of
      transcript levels of 12 selected candidate reference genes in a range of
      gametophytic P. patens structures at different developmental stages, and in P.
      patens protonemata treated with hormones or hormone transport inhibitors.
      Analysis of these RT qPCR data using GeNorm and NormFinder software resulted in
      the identification of sets of P. patens reference genes suitable for gene
      expression analysis under all tested conditions, and suggested that the two best
      reference genes are sufficient for effective data normalization under each of
      these conditions. 

PMID- 23951064
TI  - The severity of nocturnal hypoxia but not abdominal adiposity is associated with
      insulin resistance in non-obese men with sleep apnea.
AB  - BACKGROUND: Beyond obesity, sleep apnea syndrome is frequently associated with
      excess abdominal adiposity that could contribute to the deteriorated
      cardiometabolic risk profile of apneic patients. METHODS: The present study
      addressed the respective contribution of the severity of sleep apnea syndrome and
      excess abdominal adiposity to the cardiometabolic risk profile of 38 non obese
      men with polysomnography-diagnosed sleep apnea syndrome (apnea-hypopnea index >15
      events/hour). These otherwise healthy men performed a 75g-oral glucose tolerance
      test (OGTT) with plasma lipid/inflammatory and redox profiles. Twenty-one apneic
      men with high-waist circumference (>94 cm) were compared to 17 apneic men with
      low-waist circumference. RESULTS: Apneic men with high-waist circumference had
      higher AUC glucose and AUC insulin than apneic men with low-waist circumference.
      Accordingly, apneic men with high-waist circumference had higher hepatic insulin
      resistance as reflected by higher HOMA-resistance index, and lower global insulin
      sensitivity as reflected by lower insulin sensitivity index of Matsuda (derived
      from OGTT). The sleep structure and the apnea-hypopnea index were not different
      between the two groups. However, apneic men with high-waist circumference
      presented with lower mean nocturnal oxyhemoglobin (SpO2). In the 38 men, waist
      circumference and mean nocturnal SpO2 were inversely correlated (r = -0.43, p =
      0.011) and were both associated with plasma glucose/insulin homeostasis indices:
      the higher the waist circumference, the lower the mean nocturnal SpO2, the lower
      the insulin-sensitivity. Finally, in multivariable regression model, mean
      nocturnal SpO2 and not waist circumference was associated with insulin
      resistance. CONCLUSION: Thus, excess abdominal adiposity in non obese apneic men
      was associated with a deteriorated insulin-sensitivity that could be driven by a
      more severe nocturnal hypoxemia.

PMID- 23951065
TI  - Clonal dissemination, emergence of mutator lineages and antibiotic resistance
      evolution in Pseudomonas aeruginosa cystic fibrosis chronic lung infection.
AB  - Chronic respiratory infection by Pseudomonas aeruginosa is a major cause of
      mortality in cystic fibrosis (CF). We investigated the interplay between three
      key microbiological aspects of these infections: the occurrence of transmissible
      and persistent strains, the emergence of variants with enhanced mutation rates
      (mutators) and the evolution of antibiotic resistance. For this purpose, 10
      sequential isolates, covering up to an 8-year period, from each of 10 CF patients
      were studied. As anticipated, resistance significantly accumulated overtime, and
      occurred more frequently among mutator variants detected in 6 of the patients.
      Nevertheless, highest resistance was documented for the nonmutator CF epidemic
      strain LES-1 (ST-146) detected for the first time in Spain. A correlation between
      resistance profiles and resistance mechanisms evaluated [efflux pump (mexB, mexD,
      mexF, and mexY) and ampC overexpression and OprD production] was not always
      obvious and hypersusceptibility to certain antibiotics (such as aztreonam or
      meropenem) was frequently observed. The analysis of whole genome macrorestriction
      fragments through Pulsed-Field Gel Electrophoresis (PFGE) revealed that a single
      genotype (clone FQSE-A) produced persistent infections in 4 of the patients.
      Multilocus Sequence typing (MLST) identified clone FQSE-A as the CF epidemic
      clone ST-274, but striking discrepancies between PFGE and MLST profiles were
      evidenced. While PFGE macrorestriction patterns remained stable, a new sequence
      type (ST-1089) was detected in two of the patients, differing from ST-274 by only
      two point mutations in two of the genes, each leading to a nonpreviously
      described allele. Moreover, detailed genetic analyses revealed that the new ST
      1089 is a mutS deficient mutator lineage that evolved from the epidemic strain ST
      274, acquired specific resistance mechanisms, and underwent further interpatient
      spread. Thus, presented results provide the first evidence of interpatient
      dissemination of mutator lineages and denote their potential for unexpected short
      term sequence type evolution, illustrating the complexity of P. aeruginosa
      population biology in CF. 

PMID- 23951067
TI  - The implications of habitat management on the population viability of the
      endangered Ohlone tiger beetle (Cicindela ohlone) metapopulation.
AB  - Despite their role in providing ecosystem services, insects remain overlooked in
      conservation planning, and insect management approaches often lack a rigorous
      scientific basis. The endangered Ohlone tiger beetle (Cicindela ohlone) occurs in
      a 24-km(2) area in Santa Cruz County, California. The once larger metapopulation
      now consists of subpopulations inhabiting five patches of coastal prairie where
      it depends on bare ground for mating, foraging, and oviposition. Human activities
      have eliminated natural disturbances and spread invasive grasses, reducing C.
      ohlone's bare-ground habitat. Management actions to restore critical beetle
      habitat consist of cattle and horse grazing, maintaining slow bicycle speeds on
      occupied public trails, and artificial creation of bare-ground plots.
      Recreational biking trails help maintain bare ground, but can cause beetle
      mortality if left unregulated. We tracked C. ohlone survivorship and estimated
      fecundity for three years. We then constructed a stage-structured population
      projection matrix model to estimate population viability among the five patches,
      and to evaluate the success of management interventions. We demonstrate that
      habitat creation, regulation of bicycle speed, and migration between patches
      increase C. ohlone survival and population viability. Our results can be directly
      applied to management actions for conservation outcomes that will reduce species
      extinction risk and promote recolonization of extirpated patches. 

PMID- 23951066
TI  - Fusion of mature HIV-1 particles leads to complete release of a gag-GFP-based
      content marker and raises the intraviral pH.
AB  - By imaging the release of a GFP-based viral content marker produced upon virus
      maturation, we have previously found that HIV-1 fuses with endosomes. In
      contrast, fusion at the cell surface did not progress beyond a lipid mixing stage
      (hemifusion). However, recent evidence suggesting that free GFP can be trapped
      within the mature HIV-1 capsid raises concerns that this content marker may not
      be released immediately after the formation of a fusion pore. To determine
      whether a significant portion of GFP is trapped in the mature capsid, we first
      permeabilized the viral membrane with saponin. The overwhelming majority of
      pseudoviruses fully released GFP while the remaining particles exhibited partial
      loss or no loss of content. The extent of GFP release correlated with HIV-1
      maturation, implying that incomplete Gag processing, but not GFP entrapment by
      mature capsids, causes partial content release. Next, we designed a complementary
      assay for visualizing pore formation by monitoring the intraviral pH with an
      additional pH-sensitive fluorescent marker. The loss of GFP through saponin
      mediated pores was associated with a concomitant increase in the intraviral pH
      due to equilibration with the pH of an external buffer. We next imaged single HIV
      cell fusion and found that these events were manifested in a highly correlated
      loss of content and increase in the intraviral pH, as it equilibrated with the
      cytosolic pH. Fused or saponin-permeabilized pseudoviruses that partially lost
      GFP did not release the remaining content marker under conditions expected to
      promote the capsid dissociation. We were thus unable to detect significant
      entrapment of GFP by the mature HIV-1 capsid. Together, our results validate the
      use of the GFP-based content marker for imaging single virus fusion and inferring
      the sites of HIV-1 entry. 

PMID- 23951068
TI  - Influence of enamel matrix derivative on cells at different maturation stages of
      differentiation.
AB  - Enamel matrix derivative (EMD), a porcine extract harvested from developing
      porcine teeth, has been shown to promote formation of new cementum, periodontal
      ligament and alveolar bone. Despite its widespread use, an incredibly large
      variability among in vitro studies has been observed. The aim of the present
      study was to determine the influence of EMD on cells at different maturation
      stages of osteoblast differentiation by testing 6 cell types to determine if cell
      phenotype plays a role in cell behaviour following treatment with EMD. Six cell
      types including MC3T3-E1 pre-osteoblasts, rat calvarial osteoblasts, human
      periodontal ligament (PDL) cells, ROS cells, MG63 cells and human alveolar
      osteoblasts were cultured in the presence or absence of EMD and proliferation
      rates were quantified by an MTS assay. Gene expression of collagen1(COL1),
      alkaline phosphate(ALP) and osteocalcin(OC) were investigated by real-time PCR.
      While EMD significantly increased cell proliferation of all cell types, its
      effect on osteoblast differentiation was more variable. EMD significantly up
      regulated gene expression of COL1, ALP and OC in cells early in their
      differentiation process when compared to osteoblasts at later stages of
      maturation. Furthermore, the effect of cell passaging of primary human PDL cells
      (passage 2 to 15) was tested in response to treatment with EMD. EMD significantly
      increased cell proliferation and differentiation of cells at passages 2-5 however
      had completely lost their ability to respond to EMD by passages 10+. The results
      from the present study suggest that cell stimulation with EMD has a more
      pronounced effect on cells earlier in their differentiation process and may
      partially explain why treatment with EMD primarily favors regeneration of
      periodontal defects (where the periodontal ligament contains a higher number of
      undifferentiated progenitor cells) over regeneration of pure alveolar bone
      defects containing no periodontal ligament and a more limited number of
      osteoprogenitor cells. 

PMID- 23951070
TI  - Short-term curative effect of endovascular stent-graft treatment for aortic
      diseases in China: a systematic review.
AB  - INTRODUCTION: We analyzed the short-term efficacy of endovascular treatment for
      aortic diseases by summarizing all available published data on endovascular stent
      graft treatment for abdominal aortic aneurysm (AAA), thoracic aortic aneurysm
      (TAA), type A aortic dissection (type A AD) and type B aortic dissection (type B
      AD) in China. METHODS: We performed a systematic analysis of 935 published series
      on retrograde endovascular treatment for aortic diseases in China from January
      1996 to November 2010. Based on the inclusion criteria, 159 studies, involving a
      total of 5531 patients, were included. RESULTS: There were no significant
      differences in procedural success among the studies (P>0.05). The rates of
      overall neurologic complications and stroke were significantly different in all
      two-group comparisons (P<0.01). The type A AD patients had the highest rates of
      neurologic complications (both 6.67+/-0.00%), and the AAA patients had the lowest
      rates (0.31+/-0.04% and 0.11+/-0.02%). Significant differences were noted in the
      rates of cardiac, renal, pulmonary and visceral complications, which were all
      higher in the type A AD patients than in the other three groups (P<0.01). The
      endoleak rate was highest in the TAA patients (19.27+/-5.74%) and was similar in
      the type A AD patients (P>0.05). A significant difference was noted between the
      30-day mortality rate of the type A AD patients and the AAA or type B AD patients
      (P<0.05). CONCLUSION: Endovascular stent-graft is a feasible and safe treatment
      for aortic diseases, with high procedural success and low incidences of post
      procedural complications and short-term mortality. Endovascular treatment for AAA
      and type B AD is more efficient than for type A AD and TAA.

PMID- 23951069
TI  - Aberrant functional connectivity of resting state networks in transient ischemic
      attack.
AB  - BACKGROUND: Transient ischemic attack (TIA) is usually defined as a neurologic
      ischemic disorder without permanent cerebral infarction. Studies have showed that
      patients with TIA can have lasting cognitive functional impairment. Inherent
      brain activity in the resting state is spatially organized in a set of specific
      coherent patterns named resting state networks (RSNs), which epitomize the
      functional architecture of memory, language, attention, visual, auditory and
      somato-motor networks. Here, we aimed to detect differences in RSNs between TIA
      patients and healthy controls (HCs). METHODS: Twenty one TIA patients suffered an
      ischemic event and 21 matched HCs were enrolled in the study. All subjects were
      investigated using cognitive tests, psychiatric tests and functional magnetic
      resonance imaging (fMRI). Independent component analysis (ICA) was adopted to
      acquire the eight brain RSNs. Then one-sample t-tests were calculated in each
      group to gather the spatial maps of each RSNs, followed by second level analysis
      to investigate statistical differences on RSNs between twenty one TIA patients
      and 21 controls. Furthermore, a correlation analysis was performed to explore the
      relationship between functional connectivity (FC) and cognitive and psychiatric
      scales in TIA group. RESULTS: Compared with the controls, TIA patients exhibited
      both decreased and increased functional connectivity in default mode network
      (DMN) and self-referential network (SRN), and decreased functional connectivity
      in dorsal attention network (DAN), central-executive network (CEN), core network
      (CN), somato-motor network (SMN), visual network (VN) and auditory network (AN).
      There was no correlation between neuropsychological scores and functional
      connectivity in regions of RSNs. CONCLUSIONS: We observed selective impairments
      of RSN intrinsic FC in TIA patients, whose all eight RSNs had aberrant functional
      connectivity. These changes indicate that TIA is a disease with widely abnormal
      brain networks. Our results might put forward a novel way to look into neuro
      pathophysiological mechanisms in TIA patients.

PMID- 23951071
TI  - Vestibular lesion-induced developmental plasticity in spinal locomotor networks
      during Xenopus laevis metamorphosis.
AB  - During frog metamorphosis, the vestibular sensory system remains unchanged, while
      spinal motor networks undergo a massive restructuring associated with the
      transition from the larval to adult biomechanical system. We investigated in
      Xenopus laevis the impact of a pre- (tadpole stage) or post-metamorphosis
      (juvenile stage) unilateral labyrinthectomy (UL) on young adult swimming
      performance and underlying spinal locomotor circuitry. The acute disruptive
      effects on locomotion were similar in both tadpoles and juvenile frogs. However,
      animals that had metamorphosed with a preceding UL expressed restored swimming
      behavior at the juvenile stage, whereas animals lesioned after metamorphosis
      never recovered. Whilst kinematic and electrophysiological analyses of the
      propulsive system showed no significant differences in either juvenile group, a
      3D biomechanical simulation suggested that an asymmetry in the dynamic control of
      posture during swimming could account for the behavioral restoration observed in
      animals that had been labyrinthectomized before metamorphosis. This hypothesis
      was subsequently supported by in vivo electromyography during free swimming and
      in vitro recordings from isolated brainstem/spinal cord preparations.
      Specifically, animals lesioned prior to metamorphosis at the larval stage
      exhibited an asymmetrical propulsion/posture coupling as a post-metamorphic young
      adult. This developmental alteration was accompanied by an ipsilesional decrease
      in propriospinal coordination that is normally established in strict left-right
      symmetry during metamorphosis in order to synchronize dorsal trunk muscle
      contractions with bilateral hindlimb extensions in the swimming adult. Our data
      thus suggest that a disequilibrium in descending vestibulospinal information
      during Xenopus metamorphosis leads to an altered assembly of adult spinal
      locomotor circuitry. This in turn enables an adaptive compensation for the
      dynamic postural asymmetry induced by the vestibular imbalance and the
      restoration of functionally-effective behavior. 

PMID- 23951072
TI  - NCI-H295R, a human adrenal cortex-derived cell line, expresses purinergic
      receptors linked to Ca2+-mobilization/influx and cortisol secretion.
AB  - Purinergic receptor expression and involvement in steroidogenesis were examined
      in NCI-H295R (H295R), a human adrenal cortex cell line which expresses all the
      key enzymes necessary for steroidogenesis. mRNA/protein for multiple P1 (A(2A)
      and A(2B)), P2X (P2X5 and P2X7), and P2Y (P2Y1, P2Y2, P2Y6, P2Y12, P2Y13, and
      P2Y14) purinergic receptors were detected in H295R. 2MeS-ATP (10-1000 uM), a P2Y1
      agonist, induced glucocorticoid (GC) secretion in a dose-dependent manner, while
      other extracellular purine/pyrimidine agonists (1-1000 uM) had no distinct effect
      on GC secretion. Extracellular purines, even non-steroidogenic ones, induced Ca2+
      mobilization in the cells, independently of the extracellular Ca2+ concentration.
      Increases in intracellular Ca2+ concentration induced by extracellular purine
      agonists were transient, except when induced by ATP or 2MeS-ATP. Angiotensin II
      (AngII: 100 nM) and dibutyryl-cyclic AMP (db-cAMP: 500 uM) induced both GC
      secretion and Ca2+-mobilization in the presence of extracellular Ca2+ (1.2 mM).
      GC secretion by AngII was reduced by nifedipine (10-100 uM); whereas the Ca2+
      channel blocker did not inhibit GC secretion by 2MeS-ATP. Thapsigargin followed
      by extracellular Ca2+ exposure induced Ca2+-influx in H295R, and the cells
      expressed mRNA/protein of the component molecules for store-operated calcium
      entry (SOCE): transient receptor C (TRPC) channels, calcium release-activated
      calcium channel protein 1 (Orai-1), and the stromal interaction molecule 1
      (STIM1). In P2Y1-knockdown, 2MeS-ATP-induced GC secretion was significantly
      inhibited. These results suggest that H295R expresses a functional P2Y1
      purinergic receptor for intracellular Ca2+-mobilization, and that P2Y1 is linked
      to SOCE-activation, leading to Ca2+-influx which might be necessary for
      glucocorticoid secretion.

PMID- 23951073
TI  - The N-terminally truncated u3 and u3-like opioid receptors are transcribed from a
      novel promoter upstream of exon 2 in the human OPRM1 gene.
AB  - The human u opioid receptor gene, OPRM1, produces a multitude of alternatively
      spliced transcripts encoding full-length or truncated receptor variants with
      distinct pharmacological properties. The majority of these transcripts are
      transcribed from the main promoter upstream of exon 1, or from alternate
      promoters associated with exons 11 and 13. Two distinct transcripts encoding six
      transmembrane domain (6TM) hMOR receptors, u3 and u3-like, have been reported,
      both starting with the first nucleotide in exon 2. However, no mechanism
      explaining their initiation at exon 2 has been presented. Here we have used RT
      PCR with RNA from human brain tissues to demonstrate that the u3 and u3-like
      transcripts contain nucleotide sequences from the intron 1-exon 2 boundary and
      are transcribed from a novel promoter located upstream of exon 2. Reporter gene
      assays confirmed the ability of the novel promoter to drive transcription in
      human cells, albeit at low levels. We also report the identification of a "full
      length" seven transmembrane domain (7TM) version of u3, hMOR-1A2, which also
      contains exon 1, and a novel transcript, hMOR-1Y2, with the potential to encode
      the previously reported hMOR-1Y receptor, but with exon Y spliced to exon 4
      instead of exon 5 as in hMOR-1Y. Heterologous expression of GFP-tagged hMOR
      variants in HEK 293 cells showed that both 6TM receptors were retained in the
      intracellular compartment and were unresponsive to exogenous opioid exposure as
      assessed by their ability to redistribute or affect cellular cAMP production, or
      to promote intracellular Ca(2+) release. Co-staining with an antibody specific
      for endoplasmic reticulum (ER) indicated that the u3-like receptor was retained
      at the ER after synthesis. 7TM receptors hMOR-1A2 and hMOR-1Y2 resided in the
      plasma membrane, and were responsive to opioids. Notably, hMOR-1A2 exhibits novel
      functional properties in that it did not internalize in response to the opioid
      peptide [D-Ala2, N-Me-Phe4, Gly-ol5]enkephalin (DAMGO). 

PMID- 23951074
TI  - Short-chain fructo-oligosaccharides modulate intestinal microbiota and metabolic
      parameters of humanized gnotobiotic diet induced obesity mice.
AB  - Prebiotic fibres like short-chain fructo-oligosaccharides (scFOS) are known to
      selectively modulate the composition of the intestinal microbiota and especially
      to stimulate Bifidobacteria. In parallel, the involvement of intestinal
      microbiota in host metabolic regulation has been recently highlighted. The
      objective of the study was to evaluate the effect of scFOS on the composition of
      the faecal microbiota and on metabolic parameters in an animal model of diet
      induced obesity harbouring a human-type microbiota. Forty eight axenic C57BL/6J
      mice were inoculated with a sample of faecal human microbiota and randomly
      assigned to one of 3 diets for 7 weeks: a control diet, a high fat diet (HF, 60%
      of energy derived from fat)) or an isocaloric HF diet containing 10% of scFOS (HF
      scFOS). Mice fed with the two HF gained at least 21% more weight than mice from
      the control group. Addition of scFOS partially abolished the deposition of fat
      mass but significantly increased the weight of the caecum. The analysis of the
      taxonomic composition of the faecal microbiota by FISH technique revealed that
      the addition of scFOS induced a significant increase of faecal Bifidobacteria and
      the Clostridium coccoides group whereas it decreased the Clostridium leptum
      group. In addition to modifying the composition of the faecal microbiota, scFOS
      most prominently affected the faecal metabolome (e.g. bile acids derivatives,
      hydroxyl monoenoic fatty acids) as well as urine, plasma hydrophilic and plasma
      lipid metabolomes. The increase in C. coccoides and the decrease in C. leptum,
      were highly correlated to these metabolic changes, including insulinaemia, as
      well as to the weight of the caecum (empty and full) but not the increase in
      Bifidobacteria. In conclusion scFOS induce profound metabolic changes by
      modulating the composition and the activity of the intestinal microbiota, that
      may partly explain their effect on the reduction of insulinaemia. 

PMID- 23951075
TI  - Molecular hydrogen is involved in phytohormone signaling and stress responses in
      plants.
AB  - Molecular hydrogen (H2) metabolism in bacteria and algae has been well studied
      from an industrial perspective because H2 is viewed as a potential future energy
      source. A number of clinical trials have recently reported that H2 is a
      therapeutic antioxidant and signaling molecule. Although H2 metabolism in higher
      plants was reported in some early studies, its biological effects remain unclear.
      In this report, the biological effects of H2 and its involvement in plant hormone
      signaling pathways and stress responses were determined. Antioxidant enzyme
      activity was found to be increased and the transcription of corresponding genes
      altered when the effects of H2 on the germination of mung bean seeds treated with
      phytohormones was investigated. In addition, upregulation of several phytohormone
      receptor genes and genes that encode a few key factors involved in plant
      signaling pathways was detected in rice seedlings treated with HW. The
      transcription of putative rice hydrogenase genes, hydrogenase activity, and
      endogenous H2 production were also determined. H2 production was found to be
      induced by abscisic acid, ethylene, and jasmonate acid, salt, and drought stress
      and was consistent with hydrogenase activity and the expression of putative
      hydrogenase genes in rice seedlings. Together, these results suggest that H2 may
      have an effect on rice stress tolerance by modulating the output of hormone
      signaling pathways. 

PMID- 23951076
TI  - Enamel matrix derivative inhibits adipocyte differentiation of 3T3-L1 cells via
      activation of TGF-betaRI kinase activity.
AB  - Enamel matrix derivative (EMD), an extract of fetal porcine enamel, and TGF-beta
      can both suppress adipogenic differentiation. However, there have been no studies
      that functionally link the role of EMD and TGF-beta in vitro. Herein, we examined
      whether TGF-beta signaling contributes to EMD-induced suppression of adipogenic
      differentiation. Adipogenesis was studied with 3T3-L1 preadipocytes in the
      presence of SB431542, an inhibitor of TGF-betaRI kinase activity. SB431542
      reversed the inhibitory effect of EMD on adipogenic differentiation, based on Oil
      Red O staining and mRNA expression of lipid regulated genes. SB431542 also
      reduced EMD-stimulated expression of connective tissue growth factor (CTGF), an
      autocrine inhibitor of adipogenic differentiation. Moreover, short interfering
      (si)RNAs for CTGF partially reversed the EMD-induced suppression of lipid
      regulated genes. We conclude that the TGF-betaRI - CTGF axis is involved in the
      anti-adipogenic effects of EMD in vitro. 

PMID- 23951077
TI  - Epidemiological survey of quantitative ultrasound in risk assessment of falls in
      middle-aged and elderly people.
AB  - The risk assessment of falls is important, but still unsatisfactory and time
      consuming. Our objective was to assess quantitative ultrasound (QUS) in the risk
      assessment of falls. Our study was designed as epidemiological cross-sectional
      study occurring from March 2009 to February 2010 by community survey at a medical
      center. The participants were collected from systemic sample of 1,200 community
      dwelling people (Male/Female = 524/676) 40 years old and over in Yunlin County,
      Mid-Taiwan. Structural questionnaires including socioeconomic status, living
      status, smoking and drinking habits, exercise and medical history were completed.
      Quantitative ultrasound (QUS) at the non-dominant distal radial area (QUS-R) and
      the left calcaneal area (QUS-C) were measured. The overall prevalence of falls
      was 19.8%. In men, the independently associated factors for falls were age (OR:
      1.04; 95%CI: 1.01~1.06), fracture history (OR: 1.89; 95%CI: 1.12~3.19),
      osteoarthritis history (OR: 3.66; 95%CI: 1.15~11.64) and speed of sound (OR:
      0.99; 95%CI: 0.99~1.00; p<0.05) by QUS-R. In women, the independently associated
      factors for falls were current drinking (OR: 3.54; 95%CI: 1.35~9.31) and
      broadband ultrasound attenuation (OR: 0.98; 95%CI: 0.97~0.99; p<0.01) by QUS-C.
      The cutoffs at -2.5< T-score<-1 derived using QUS-R (OR: 2.85; 95%CI: 1.64~4.96;
      p<0.01) in men or T-score ?-2.5 derived using QUS-C (OR: 2.72; 95%CI: 1.42~5.21;
      p<0.01) in women showed an independent association with falls. The lowest T-score
      derived using either QUS-R or QUS-C was also revealed as an independent factor
      for falls in both men (OR: 2.13; 95%CI: 1.03~4.43; p<0.05) and women (OR: 2.36;
      95%CI: 1.13~4.91; p<0.05). CONCLUSIONS: Quantitative ultrasounds, measured either
      at the radial or calcaneal area, are convenient tools by which to assess the risk
      of falls in middle-aged and elderly people.

PMID- 23951078
TI  - De novo assembly and characterization of the transcriptome, and development of
      SSR markers in wax gourd (Benicasa hispida).
AB  - BACKGROUND: Wax gourd is a widely used vegetable of Cucuribtaceae, and also has
      important medicinal and health values. However, the genomic resources of wax
      gourd were scarcity, and only a few nucleotide sequences could be obtained in
      public databases. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we examined
      transcriptome in wax gourd. More than 44 million of high quality reads were
      generated from five different tissues of wax gourd using Illumina paired-end
      sequencing technology. Approximately 4 Gbp data were generated, and de novo
      assembled into 65,059 unigenes, with an N50 of 1,132 bp. Based on sequence
      similarity search with known protein database, 36,070 (55.4%) showed significant
      similarity to known proteins in Nr database, and 24,969 (38.4%) had BLAST hits in
      Swiss-Prot database. Among the annotated unigenes, 14,994 of wax gourd unigenes
      were assigned to GO term annotation, and 23,977 were found to have COG
      classifications. In addition, a total of 18,713 unigenes were assigned to 281
      KEGG pathways. Furthermore, 6,242 microsatellites (simple sequence repeats) were
      detected as potential molecular markers in wax gourd. Two hundred primer pairs
      for SSRs were designed for validation of the amplification and polymorphism. The
      result showed that 170 of the 200 primer pairs were successfully amplified and 49
      (28.8%) of them exhibited polymorphisms. CONCLUSION/SIGNIFICANCE: Our study
      enriches the genomic resources of wax gourd and provides powerful information for
      future studies. The availability of this ample amount of information about the
      transcriptome and SSRs in wax gourd could serve as valuable basis for studies on
      the physiology, biochemistry, molecular genetics and molecular breeding of this
      important vegetable crop.

PMID- 23951079
TI  - Characteristics of rod regeneration in a novel zebrafish retinal degeneration
      model using N-methyl-N-nitrosourea (MNU).
AB  - Primary loss of photoreceptors caused by diseases such as retinitis pigmentosa is
      one of the main causes of blindness worldwide. To study such diseases, rodent
      models of N-methyl-N-nitrosourea (MNU)-induced retinal degeneration are widely
      used. As zebrafish (Danio rerio) are a popular model system for visual research
      that offers persistent retinal neurogenesis throughout the lifetime and retinal
      regeneration after severe damage, we have established a novel MNU-induced model
      in this species. Histology with staining for apoptosis (TUNEL), proliferation
      (PCNA), activated Muller glial cells (GFAP), rods (rhodopsin) and cones (zpr-1)
      were performed. A characteristic sequence of retinal changes was found. First,
      apoptosis of rod photoreceptors occurred 3 days after MNU treatment and resulted
      in a loss of rod cells. Consequently, proliferation started in the inner nuclear
      layer (INL) with a maximum at day 8, whereas in the outer nuclear layer (ONL) a
      maximum was observed at day 15. The proliferation in the ONL persisted to the end
      of the follow-up (3 months), interestingly, without ongoing rod cell death. We
      demonstrate that rod degeneration is a sufficient trigger for the induction of
      Muller glial cell activation, even if only a minimal number of rod cells undergo
      cell death. In conclusion, the use of MNU is a simple and feasible model for rod
      photoreceptor degeneration in the zebrafish that offers new insights into rod
      regeneration. 

PMID- 23951081
TI  - Do cultivated varieties of native plants have the ability to outperform their
      wild relatives?
AB  - Vast amounts of cultivars of native plants are annually introduced into the semi
      natural range of their wild relatives for re-vegetation and restoration. As
      cultivars are often selected towards enhanced biomass production and might
      transfer these traits into wild relatives by hybridization, it is suggested that
      cultivars and the wild * cultivar hybrids are competitively superior to their
      wild relatives. The release of such varieties may therefore result in unintended
      changes in native vegetation. In this study we examined for two species
      frequently used in re-vegetation (Plantago lanceolata and Lotus corniculatus)
      whether cultivars and artificially generated intra-specific wild * cultivar
      hybrids may produce a higher vegetative and generative biomass than their wilds.
      For that purpose a competition experiment was conducted for two growing seasons
      in a common garden. Every plant type was growing (a.) alone, (b.) in pairwise
      combination with a similar plant type and (c.) in pairwise interaction with a
      different plant type. When competing with wilds cultivars of both species showed
      larger biomass production than their wilds in the first year only and hybrids
      showed larger biomass production than their wild relatives in both study years.
      As biomass production is an important factor determining fitness and competitive
      ability, we conclude that cultivars and hybrids are competitively superior their
      wild relatives. However, cultivars of both species experienced large fitness
      reductions (nearly complete mortality in L. corniculatus) due to local climatic
      conditions. We conclude that cultivars are good competitors only as long as they
      are not subjected to stressful environmental factors. As hybrids seemed to
      inherit both the ability to cope with the local climatic conditions from their
      wild parents as well as the enhanced competitive strength from their cultivars,
      we regard them as strong competitors and assume that they are able to outperform
      their wilds at least over the short-term. 

PMID- 23951080
TI  - Alterations in hypothalamus-pituitary-adrenal/thyroid axes and gonadotropin
      releasing hormone in the patients with primary insomnia: a clinical research.
AB  - The hypothalamus-pituitary-target gland axis is thought to be linked with
      insomnia, yet there has been a lack of further systematic studies to prove this.
      This study included 30 patients with primary insomnia (PI), 30 patients with
      depression-comorbid insomnia (DCI), and 30 healthy controls for exploring the
      alterations in the hypothalamus-pituitary-adrenal/thyroid axes' hormones and
      gonadotropin-releasing hormone (GnRH). The Pittsburgh Sleep Quality Index was
      used to evaluate sleep quality in all subjects. The serum concentrations of
      corticotrophin-releasing hormone (CRH), thyrotrophin-releasing hormone (TRH),
      GnRH, adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH),
      cortisol, total triiodothyronine (TT3), and total thyroxine (TT4) in the morning
      (between 0730 h and 0800 h) were detected. Compared to the controls, all hormonal
      levels were elevated in the insomniacs, except ACTH and TSH in the PI group.
      Compared to the DCI patients, the PI patients had higher levels of CRH, cortisol,
      TT3, and TT4 but lower levels of TRH, GnRH, and ACTH. Spearman's correlation
      analysis indicated that CRH, TRH, GnRH, TSH, cortisol, TT4, and TT3 were
      positively correlated with the severity of insomnia. The linear regression
      analysis showed that only CRH, GnRH, cortisol, and TT3 were affected by the PSQI
      scores among all subjects, and only CRH was included in the regression model by
      the "stepwise" method in the insomnia patients. Our results indicated that PI
      patients may have over-activity of the hypothalamus-pituitary-adrenal/thyroid
      axes and an elevated level of GnRH in the morning. 

PMID- 23951082
TI  - Fine mapping of the pond snail left-right asymmetry (chirality) locus using RAD
      Seq and fibre-FISH.
AB  - The left-right asymmetry of snails, including the direction of shell coiling, is
      determined by the delayed effect of a maternal gene on the chiral twist that
      takes place during early embryonic cell divisions. Yet, despite being a well
      established classical problem, the identity of the gene and the means by which
      left-right asymmetry is established in snails remain unknown. We here demonstrate
      the power of new genomic approaches for identification of the chirality gene,
      "D". First, heterozygous (Dd) pond snails Lymnaea stagnalis were self-fertilised
      or backcrossed, and the genotype of more than six thousand offspring inferred,
      either dextral (DD/Dd) or sinistral (dd). Then, twenty of the offspring were used
      for Restriction-site-Associated DNA Sequencing (RAD-Seq) to identify anonymous
      molecular markers that are linked to the chirality locus. A local genetic map was
      constructed by genotyping three flanking markers in over three thousand snails.
      The three markers lie either side of the chirality locus, with one very tightly
      linked (<0.1 cM). Finally, bacterial artificial chromosomes (BACs) were isolated
      that contained the three loci. Fluorescent in situ hybridization (FISH) of
      pachytene cells showed that the three BACs tightly cluster on the same bivalent
      chromosome. Fibre-FISH identified a region of greater that ~0.4 Mb between two
      BAC clone markers that must contain D. This work therefore establishes the
      resources for molecular identification of the chirality gene and the variation
      that underpins sinistral and dextral coiling. More generally, the results also
      show that combining genomic technologies, such as RAD-Seq and high resolution
      FISH, is a robust approach for mapping key loci in non-model systems. 

PMID- 23951083
TI  - Establishment and characterization of primary glioblastoma cell lines from fresh
      and frozen material: a detailed comparison.
AB  - BACKGROUND: Development of clinically relevant tumor model systems for
      glioblastoma multiforme (GBM) is important for advancement of basic and
      translational biology. High molecular heterogeneity of GBM tumors is well
      recognized, forming the rationale for molecular tests required before
      administration of several of the novel therapeutics rapidly entering the clinics.
      One model that has gained wide acceptance is the primary cell culture model. The
      laborious and time consuming process is rewarded with a relative high success
      rate (about 60%). We here describe and evaluate a very simple cryopreservation
      procedure for GBM tissue prior to model establishment that will considerably
      reduce the logistic complexity. METHODS: Twenty-seven GBM samples collected ad
      hoc were prepared for primary cell culture freshly from surgery (#1) and after
      cryopreservation (#2). RESULTS: Take rates after cryopreservation (59%) were as
      satisfactory as from fresh tissue (63%; p = 1.000). We did not observe any
      relevant molecular or phenotypic differences between cell lines established from
      fresh or vitally frozen tissue. Further, sensitivity both towards standard
      chemotherapeutic agents (Temozolomide, BCNU and Vincristine) and novel agents
      like the receptor tyrosine kinase inhibitor Imatinib did not differ. CONCLUSIONS:
      Our simple cryopreservation procedure facilitates collection, long-time storage
      and propagation (modeling) of clinical GBM specimens (potentially also from
      distant centers) for basic research, (pre-) clinical studies of novel therapies
      and individual response prediction.

PMID- 23951084
TI  - A protective and safe intranasal RSV vaccine based on a recombinant prefusion
      like form of the F protein bound to bacterium-like particles.
AB  - Respiratory syncytial virus (RSV) is an important cause of respiratory tract
      disease in infants and the elderly. Currently, no licensed vaccine against RSV is
      available. Here we describe the development of a safe and effective intranasal
      subunit vaccine that is based on recombinant fusion (F) protein bound to the
      surface of immunostimulatory bacterium-like particles (BLPs) derived from the
      food-grade bacterium Lactococcus lactis. Different variants of F were analyzed
      with respect to their conformation and reactivity with neutralizing antibodies,
      assuming that F proteins mimicking the metastable prefusion form of RSV F expose
      a more extensive and relevant epitope repertoire than F proteins corresponding to
      the postfusion structure. Our results indicate that the recombinant soluble
      ectodomain of RSV F readily adopts a postfusion conformation, generation of which
      cannot be prevented by C-terminal addition of a trimerization motif, but whose
      formation is prevented by mutation of the two furin cleavage sites in F. While
      the putative postfusion form of F is recognized well by the monoclonal antibody
      Palivizumab, this is much less so for the more potently neutralizing, prefusion
      specific antibodies D25 and AM22. Both addition of the trimerization motif and
      mutation of the furin cleavage sites increased the reactivity of F with D25 and
      AM22, with the highest reactivity being observed for F proteins in which both
      these features were combined. Intranasal vaccination of mice or cotton rats with
      BLPs loaded with this latter prefusion-like F protein (BLP-F), resulted in the
      potent induction of F-specific immunoglobulins and in significantly decreased
      virus titers in the lungs upon RSV challenge. Moreover, and in contrast to
      animals vaccinated with formalin-inactivated RSV, animals that received BLP-F
      exhibited high levels of F-specific secretory IgA in the nose and RSV
      neutralizing antibodies in sera, but did not show symptoms of enhanced disease
      after challenge with RSV. 

PMID- 23951085
TI  - Lentiviral vector-mediated gradients of GDNF in the injured peripheral nerve:
      effects on nerve coil formation, Schwann cell maturation and myelination.
AB  - Although the peripheral nerve is capable of regeneration, only a small minority
      of patients regain normal function after surgical reconstruction of a major
      peripheral nerve lesion, resulting in a severe and lasting negative impact on the
      quality of life. Glial cell-line derived neurotrophic factor (GDNF) has potent
      survival- and outgrowth-promoting effects on motoneurons, but locally elevated
      levels of GDNF cause trapping of regenerating axons and the formation of nerve
      coils. This phenomenon has been called the "candy store" effect. In this study we
      created gradients of GDNF in the sciatic nerve after a ventral root avulsion.
      This approach also allowed us to study the effect of increasing concentrations of
      GDNF on Schwann cell proliferation and morphology in the injured peripheral
      nerve. We demonstrate that lentiviral vectors can be used to create a 4 cm long
      GDNF gradient in the intact and lesioned rat sciatic nerve. Nerve coils were
      formed throughout the gradient and the number and size of the nerve coils
      increased with increasing GDNF levels in the nerve. In the nerve coils, Schwann
      cell density is increased, their morphology is disrupted and myelination of axons
      is severely impaired. The total number of regenerated and surviving motoneurons
      is not enhanced after the distal application of a GDNF gradient, but increased
      sprouting does result in higher number of motor axon in the distal segment of the
      sciatic nerve. These results show that lentiviral vector mediated overexpression
      of GDNF exerts multiple effects on both Schwann cells and axons and that nerve
      coil formation already occurs at relatively low concentrations of exogenous GDNF.
      Controlled expression of GDNF, by using a viral vector with regulatable GDNF
      expression, may be required to avoid motor axon trapping and to prevent the
      effects on Schwann cell proliferation and myelination. 

PMID- 23951086
TI  - The E3 ligase AtRDUF1 positively regulates salt stress responses in Arabidopsis
      thaliana.
AB  - Ubiquitination is an important post-translational protein modification that is
      known to play critical roles in diverse biological processes in eukaryotes. The
      RING E3 ligases function in ubiquitination pathways, and are involved in a large
      diversity of physiological processes in higher plants. The RING domain-containing
      E3 ligase AtRDUF1 was previously identified as a positive regulator of ABA
      mediated dehydration stress response in Arabidopsis. In this study, we report
      that AtRDUF1 is involved in plant responses to salt stress. AtRDUF1 expression is
      upregulated by salt treatment. Overexpression of AtRDUF1 in Arabidopsis results
      in an insensitivity to salt and osmotic stresses during germination and seedling
      growth. A double knock-out mutant of AtRDUF1 and its close homolog AtRDUF2
      (atrduf1atrduf2) was hypersensitive to salt treatment. The expression levels of
      the stress-response genes RD29B, RD22, and KIN1 are more sensitive to salt
      treatment in AtRDUF1 overexpression plants. In summary, our data show that
      AtRDUF1 positively regulates responses to salt stress in Arabidopsis. 

PMID- 23951087
TI  - Targeting Rac1 signaling inhibits streptococcal M1 protein-induced CXC chemokine
      formation, neutrophil infiltration and lung injury.
AB  - Infections with Streptococcus pyogenes exhibit a wide spectrum of infections
      ranging from mild pharyngitis to severe Streptococcal toxic shock syndrome
      (STSS). The M1 serotype of Streptococcus pyogenes is most commonly associated
      with STSS. In the present study, we hypothesized that Rac1 signaling might
      regulate M1 protein-induced lung injury. We studied the effect of a Rac1
      inhibitor (NSC23766) on M1 protein-provoked pulmonary injury. Male C57BL/6 mice
      received NSC23766 prior to M1 protein challenge. Bronchoalveolar fluid and lung
      tissue were harvested for quantification of neutrophil recruitment, edema and CXC
      chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow
      cytometry. Quantitative RT-PCR was used to determine gene expression of CXC
      chemokines in alveolar macrophages. Treatment with NSC23766 decreased M1 protein
      induced neutrophil infiltration, edema formation and tissue injury in the lung.
      M1 protein challenge markedly enhanced Mac-1 expression on neutrophils and CXC
      chemokine levels in the lung. Inhibition of Rac1 activity had no effect on M1
      protein-induced expression of Mac-1 on neutrophils. However, Rac1 inhibition
      markedly decreased M1 protein-evoked formation of CXC chemokines in the lung.
      Moreover, NSC23766 completely inhibited M1 protein-provoked gene expression of
      CXC chemokines in alveolar macrophages. We conclude that these novel results
      suggest that Rac1 signaling is a significant regulator of neutrophil infiltration
      and CXC chemokine production in the lung. Thus, targeting Rac1 activity might be
      a potent strategy to attenuate streptococcal M1 protein-triggered acute lung
      damage. 

PMID- 23951088
TI  - Extremely low-frequency magnetic exposure appears to have no effect on
      pathogenesis of Alzheimer's disease in aluminum-overloaded rat.
AB  - OBJECTIVE: Extremely low-frequency magnetic field (ELF-MF) has been reported to
      be of potential pathogenetic relevance to Alzheimer's disease (AD) for years.
      However, evidence confirming this function remains inconclusive. Chronic Al
      treatment has been identified as a contributing factor to cognitive function
      impairment in AD. This study aims to examine whether or not ELF-MF and Al have
      synergistic effects toward AD pathogenesis by investigating the effects of ELF-MF
      with or without chronic Al treatment on SD rats. METHODS: Sprague-Dawley (SD)
      rats were subjected one of the following treatments: sham (control group), oral
      Al (Al group), ELF-MF (100 uT at 50 Hz) with oral Al (MF+Al group), or ELF-MF
      (100 uT at 50 Hz) without oral Al (MF group). RESULTS: After 12 wk of treatment,
      oral Al treatment groups (Al and MF+Al groups) showed learning and memory
      impairment as well as morphological hallmarks, including neuronal cell loss and
      high density of amyloid-beta (Abeta) in the hippocampus and cerebral cortex. ELF
      MF without Al treatment showed no significant effect on AD pathogenesis. ELF
      MF+Al treatment induced no more damage than Al treatment did. CONCLUSIONS: Our
      results showed no evidence of any association between ELF-MF exposure (100 uT at
      50 Hz) and AD, and ELF-MF exposure does not influence the pathogenesis of AD
      induced by Al overload.

PMID- 23951089
TI  - O-antigen protects gram-negative bacteria from histone killing.
AB  - Beyond their traditional role of wrapping DNA, histones display antibacterial
      activity to Gram-negative and -positive bacteria. To identify bacterial
      components that allow survival to a histone challenge, we selected resistant
      bacteria from homologous Escherichia coli libraries that harbor plasmids carrying
      pieces of the chromosome in different sizes. We identified genes required for
      exopolysaccharide production and for the synthesis of the polysaccharide domain
      of the lipopolysaccharide, called O-antigen. Indeed, O-antigen and
      exopolysaccharide conferred further resistance to histones. Notably, O-antigen
      also conferred resistance to histones in the pathogens Shigella flexneri and
      Klebsiella pneumoniae. 

PMID- 23951090
TI  - Efficient, long term production of monocyte-derived macrophages from human
      pluripotent stem cells under partly-defined and fully-defined conditions.
AB  - Human macrophages are specialised hosts for HIV-1, dengue virus, Leishmania and
      Mycobacterium tuberculosis. Yet macrophage research is hampered by lack of
      appropriate cell models for modelling infection by these human pathogens, because
      available myeloid cell lines are, by definition, not terminally differentiated
      like tissue macrophages. We describe here a method for deriving monocytes and
      macrophages from human Pluripotent Stem Cells which improves on previously
      published protocols in that it uses entirely defined, feeder- and serum-free
      culture conditions and produces very consistent, pure, high yields across both
      human Embryonic Stem Cell (hESC) and multiple human induced Pluripotent Stem Cell
      (hiPSC) lines over time periods of up to one year. Cumulatively, up to ~3*10(7)
      monocytes can be harvested per 6-well plate. The monocytes produced are most
      closely similar to the major blood monocyte (CD14(+), CD16(low), CD163(+)).
      Differentiation with M-CSF produces macrophages that are highly phagocytic, HIV-1
      infectable, and upon activation produce a pro-inflammatory cytokine profile
      similar to blood monocyte-derived macrophages. Macrophages are notoriously hard
      to genetically manipulate, as they recognise foreign nucleic acids; the
      lentivector system described here overcomes this, as pluripotent stem cells can
      be relatively simply genetically manipulated for efficient transgene expression
      in the differentiated cells, surmounting issues of transgene silencing. Overall,
      the method we describe here is an efficient, effective, scalable system for the
      reproducible production and genetic modification of human macrophages,
      facilitating the interrogation of human macrophage biology. 

PMID- 23951091
TI  - Angiogenic properties of human dental pulp stem cells.
AB  - Angiogenesis, the formation of capillaries from pre-existing blood vessels, is a
      key process in tissue engineering. If blood supply cannot be established rapidly,
      there is insufficient oxygen and nutrient transport and necrosis of the implanted
      tissue will occur. Recent studies indicate that the human dental pulp contains
      precursor cells, named dental pulp stem cells (hDPSC) that show self-renewal and
      multilineage differentiation capacity. Since these cells can be easily isolated,
      cultured and cryopreserved, they represent an attractive stem cell source for
      tissue engineering. Until now, only little is known about the angiogenic
      abilities and mechanisms of the hDPSC. In this study, the angiogenic profile of
      both cell lysates and conditioned medium of hDPSC was determined by means of an
      antibody array. Numerous pro-and anti-angiogenic factors such as vascular
      endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1),
      plasminogen activator inhibitor-1 (PAI-1) and endostatin were found both at the
      mRNA and protein level. hDPSC had no influence on the proliferation of the human
      microvascular endothelial cells (HMEC-1), but were able to significantly induce
      HMEC-1 migration in vitro. Addition of the PI3K-inhibitor LY294002 and the MEK
      inhibitor U0126 to the HMEC-1 inhibited this effect, suggesting that both Akt and
      ERK pathways are involved in hDPSC-mediated HMEC-1 migration. Antibodies against
      VEGF also abolished the chemotactic actions of hDPSC. Furthermore, in the chicken
      chorioallantoic membrane (CAM) assay, hDPSC were able to significantly induce
      blood vessel formation. In conclusion, hDPSC have the ability to induce
      angiogenesis, meaning that this stem cell population has a great clinical
      potential, not only for tissue engineering but also for the treatment of chronic
      wounds, stroke and myocardial infarctions. 

PMID- 23951092
TI  - Inhibition of PPARalpha induces cell cycle arrest and apoptosis, and synergizes
      with glycolysis inhibition in kidney cancer cells.
AB  - Renal cell carcinoma (RCC) is the sixth most common cancer in the US. While RCC
      is highly metastatic, there are few therapeutics options available for patients
      with metastatic RCC, and progression-free survival of patients even with the
      newest targeted therapeutics is only up to two years. Thus, novel therapeutic
      targets for this disease are desperately needed. Based on our previous
      metabolomics studies showing alteration of peroxisome proliferator-activated
      receptor alpha (PPARalpha) related events in both RCC patient and xenograft mice
      materials, this pathway was further examined in the current study in the setting
      of RCC. PPARalpha is a nuclear receptor protein that functions as a transcription
      factor for genes including those encoding enzymes involved in energy metabolism;
      while PPARalpha has been reported to regulate tumor growth in several cancers, it
      has not been evaluated in RCC. A specific PPARalpha antagonist, GW6471, induced
      both apoptosis and cell cycle arrest at G0/G1 in VHL(+) and VHL(-) RCC cell lines
      (786-O and Caki-1) associated with attenuation of the cell cycle regulatory
      proteins c-Myc, Cyclin D1, and CDK4; this data was confirmed as specific to
      PPARalpha antagonism by siRNA methods. Interestingly, when glycolysis was blocked
      by several methods, the cytotoxicity of GW6471 was synergistically increased,
      suggesting a switch to fatty acid oxidation from glycolysis and providing an
      entirely novel therapeutic approach for RCC. 

PMID- 23951093
TI  - Risks and benefits of early antithrombotic therapy after thrombolytic treatment
      in patients with acute stroke.
AB  - BACKGROUND: Current guidelines recommend withholding antithrombotic therapy (ATT)
      for at least 24 h in patients with acute ischemic stroke treated with
      thrombolytic therapy. Herein, we report a retrospective analysis of a single
      centre experience on the safety and efficacy of antithrombotic therapy (ATT)
      started before or after 24 h of intravenous thrombolysis in a cohort of acute
      ischemic stroke patients. METHODS: A total of 139 patients (Rapid ATT group)
      received antithrombotic therapy before 24 h of thrombolysis, and 33 patients
      (Standard ATT group) after 24 h. The brain parenchyma and vessel status were
      assessed using simple CT scan on admission, multimodal CT scan at the end of
      thrombolysis, and angio-CT/MRI scan at day 3. Functional outcome was scored using
      the modified Rankin Scale (mRS) at day 90. RESULTS: The two ATT groups had
      similar demographics, stroke subtypes, baseline NIHSS, thrombolytic strategies,
      vessel-patency rates at the end of thrombolysis, and incidence of bleeding
      complications at follow up. At day 3, the Rapid ATT group had a non-significant
      improved vessel-patency rate than the Standard ATT group. At day 90, a greater
      proportion of patients in the rapid ATT group had shifted down the mRS, and had
      improved in the NIHSS score. CONCLUSIONS: ATT initiated before 24 h of
      intravenous thrombolytic therapy in acute stroke patients disclosed no safety
      concerns compared with a conventional antithrombotic therapy delay of 24 h and
      showed better functional outcome at follow up. The value of early initiation of
      ATT after thrombolysis deserves further assessment in randomized controlled
      trials.

PMID- 23951094
TI  - Hospital acquired pneumonia is linked to right hemispheric peri-insular stroke.
AB  - PURPOSE: Hospital acquired pneumonia (HAP) is a major complication of stroke. We
      sought to determine associations between infarction of specific brain regions and
      HAP. METHODS: 215 consecutive acute stroke patients with HAP (2003-2009) were
      carefully matched with 215 non-pneumonia controls by gender, then NIHSS, then
      age. Admission imaging and binary masks of infarction were registered to MNI-152
      space. Regional atlas and voxel-based log-odds were calculated to assess the
      relationship between infarct location and the likelihood of HAP. An independently
      validated penalized conditional logistic regression model was used to identify
      HAP associated imaging regions. RESULTS: The HAP and control patients were well
      matched by gender (100%), age (95% within 5-years), NIHSS (98% within 1-point),
      infarct size, dysphagia, and six other clinical variables. Right hemispheric
      infarcts were more frequent in patients with HAP versus controls (43.3% vs.
      34.0%, p = 0.054), whereas left hemispheric infarcts were more frequent in
      controls (56.7% vs. 44.7%, p = 0.012); there was no significant difference
      between groups in the rate of brainstem strokes (p = 1.0). Of the 10 most
      infarcted regions, only right insular cortex volume was different in HAP versus
      controls (20 vs. 12 ml, p = 0.02). In univariate analyses, the highest log-odds
      regions for pneumonia were right hemisphere, cerebellum, and brainstem. The best
      performing multivariate model selected 7 brain regions of infarction and 2
      infarct volume-based variables independently associated with HAP. CONCLUSIONS:
      HAP is associated with right hemispheric peri-insular stroke. These associations
      may be related to autonomic modulation of immune mechanisms, supporting recent
      hypotheses of stroke mediated immune suppression.

PMID- 23951095
TI  - Methotrexate treatment causes early onset of disease in a mouse model of Ross
      River virus-induced inflammatory disease through increased monocyte production.
AB  - Part of the Togaviridae family, alphaviruses, including chikungunya virus
      (CHIKV), Sindbis virus (SINV) and Ross River virus (RRV), are able to cause
      significant inflammatory pathologies ranging from arthritis to encephalitis.
      Following symptomatic infection with arthritis-associated alphaviruses, patients
      often experience severe joint pain, affecting distal and small joints, which can
      last six months or longer. Recently, methotrexate (MTX), a disease modifying anti
      rheumatic drug (DMARD), was used to treat patients experiencing chronic rheumatic
      symptoms following infection with CHIKV. Here, the effect of MTX on Ross River
      virus disease (RRVD) in mice was examined to better understand its therapeutic
      potential for alphaviral-induced musculoskeletal disease and to further our
      knowledge of the development of alphaviral pathologies. Using a mouse model, we
      analyzed the effect of MTX on RRVD. RRV disease pathogenesis in response to MTX
      treatment was determined by measuring levels of proinflammatory factors, cellular
      infiltrates, viral titer and histological analysis of infected tissues. RRV
      infected mice receiving MTX treatment rapidly developed musculoskeletal disease,
      which correlated with a significant influx of inflammatory cell infiltrates into
      the skeletal muscle tissue. Although no difference was observed in the level of
      proinflammatory cytokines and chemokines, the viral load increased at early time
      points post infection in the serum and quadriceps of MTX treated mice, possibly
      contributing to disease pathogenesis. Results suggest that MTX treatment of acute
      RRVD in mice provides no therapeutic benefit and underline the importance of
      inflammatory monocytes in alphaviral induced arthritides. 

PMID- 23951096
TI  - Mitochondrial DNA variation and introgression in Siberian taimen Hucho taimen.
AB  - Siberian taimen Hucho taimen is the largest representative of the family
      Salmonidae inhabiting rivers of northern Eurasia. The species is under intensive
      aquaculture activity. To monitor natural taimen populations we have sequenced a
      portion (8,141 bp) of the mitochondrial (mt) genome in 28 specimens of H. taimen
      from six localities in the Amur River basin. Nucleotide variability is low (pi =
      0.0010), but structured in two divergent haplotype groups. A comparison of the
      data with the GenBank H. taimen mt genome (HQ897271) reveals significant
      differences between them in spite of the fact that the fish specimens come from
      neighboring geographical areas. The distribution of divergence is non-uniform
      with two highly pronounced divergent regions centered on two genes, ND3 and ND6.
      To clarify the pattern of divergence we sequenced the corresponding portion of
      the mt genome of lenok Brachymystax tumensis and analyzed the GenBank complete mt
      genomes of related species. We have found that the first and second divergent
      regions are identical between the GenBank H. taimen and two lenok subspecies, B.
      lenok and B. lenok tsinlingensis, respectively. Consequently, both divergent
      regions represent introgressed mtDNA resulting from intergeneric hybridization
      between the two lenok subspecies and H. taimen. Introgression is, however, not
      detected in our specimens. This plus the precise identity of the introgressed
      fragments between the donor and the recipient GenBank sequence suggests that the
      introgression is local and very recent, probably due to artificial manipulations
      involving taimen-lenok intergeneric hybridization. Human-mediated hybridization
      may become a major threat to aquatic biodiversity. Consequently we suggest that
      due attention needs to be given to this threat by means of responsible breeding
      program management, so as to prevent a potential spread of hybrid fishes that
      could jeopardize the resilience of locally adapted gene pools of the native H.
      taimen populations.

PMID- 23951097
TI  - Long lasting protein synthesis- and activity-dependent spine shrinkage and
      elimination after synaptic depression.
AB  - Neuronal circuits modify their response to synaptic inputs in an experience
      dependent fashion. Increases in synaptic weights are accompanied by structural
      modifications, and activity dependent, long lasting growth of dendritic spines
      requires new protein synthesis. When multiple spines are potentiated within a
      dendritic domain, they show dynamic structural plasticity changes, indicating
      that spines can undergo bidirectional physical modifications. However, it is
      unclear whether protein synthesis dependent synaptic depression leads to long
      lasting structural changes. Here, we investigate the structural correlates of
      protein synthesis dependent long-term depression (LTD) mediated by metabotropic
      glutamate receptors (mGluRs) through two-photon imaging of dendritic spines on
      hippocampal pyramidal neurons. We find that induction of mGluR-LTD leads to
      robust and long lasting spine shrinkage and elimination that lasts for up to 24
      hours. These effects depend on signaling through group I mGluRs, require protein
      synthesis, and activity. These data reveal a mechanism for long lasting
      remodeling of synaptic inputs, and offer potential insights into mental
      retardation. 

PMID- 23951098
TI  - CCN family member 2/connective tissue growth factor (CCN2/CTGF) has anti-aging
      effects that protect articular cartilage from age-related degenerative changes.
AB  - To examine the role of connective tissue growth factor CCN2/CTGF (CCN2) in the
      maintenance of the articular cartilaginous phenotype, we analyzed knee joints
      from aging transgenic mice (TG) overexpressing CCN2 driven by the Col2a1
      promoter. Knee joints from 3-, 14-, 40-, and 60-day-old and 5-, 12-, 18-, 21-,
      and 24-month-old littermates were analyzed. Ccn2-LacZ transgene expression in
      articular cartilage was followed by X-gal staining until 5 months of age.
      Overexpression of CCN2 protein was confirmed through all ages in TG articular
      cartilage and in growth plates. Radiographic analysis of knee joints showed a
      narrowing joint space and other features of osteoarthritis in 50% of WT, but not
      in any of the TG mice. Transgenic articular cartilage showed enhanced toluidine
      blue and safranin-O staining as well as chondrocyte proliferation but reduced
      staining for type X and I collagen and MMP-13 as compared with those parameters
      for WT cartilage. Staining for aggrecan neoepitope, a marker of aggrecan
      degradation in WT articular cartilage, increased at 5 and 12 months, but
      disappeared at 24 months due to loss of cartilage; whereas it was reduced in TG
      articular cartilage after 12 months. Expression of cartilage genes and MMPs under
      cyclic tension stress (CTS) was measured by using primary cultures of
      chondrocytes obtained from wild-type (WT) rib cartilage and TG or WT epiphyseal
      cartilage. CTS applied to primary cultures of mock-transfected rib chondrocytes
      from WT cartilage and WT epiphyseal cartilage induced expression of Col1a1,
      ColXa1, Mmp-13, and Mmp-9 mRNAs; however, their levels were not affected in CCN2
      overexpressing chondrocytes and TG epiphyseal cartilage. In conclusion, cartilage
      specific overexpression of CCN2 during the developmental and growth periods
      reduced age-related changes in articular cartilage. Thus CCN2 may play a role as
      an anti-aging factor by stabilizing articular cartilage. 

PMID- 23951100
TI  - Systemic transplantation of human adipose tissue-derived mesenchymal stem cells
      for the regeneration of irradiation-induced salivary gland damage.
AB  - OBJECTIVES: Cell-based therapy has been reported to repair or restore damaged
      salivary gland (SG) tissue after irradiation. This study was aimed at determining
      whether systemic administration of human adipose-derived mesenchymal stem cells
      (hAdMSCs) can ameliorate radiation-induced SG damage. METHODS: hAdMSCs (1 *
      10(6)) were administered through a tail vein of C3H mice immediately after local
      irradiation, and then this infusion was repeated once a week for 3 consecutive
      weeks. At 12 weeks after irradiation, functional evaluations were conducted by
      measuring salivary flow rates (SFRs) and salivation lag times, and
      histopathologic and immunofluorescence histochemistry studies were performed to
      assay microstructural changes, apoptosis, and proliferation indices. The
      engraftment and in vivo differentiation of infused hAdMSCs were also
      investigated, and the transdifferentiation of hAdMSCs into amylase-producing SG
      epithelial cells (SGCs) was observed in vitro using a co-culture system. RESULTS:
      The systemic administration of hAdMSCs exhibited improved SFRs at 12 weeks after
      irradiation. hAdMSC-transplanted SGs showed fewer damaged and atrophied acinar
      cells and higher mucin and amylase production levels than untreated irradiated
      SGs. Immunofluorescence TUNEL assays revealed fewer apoptotic cells in the hAdMSC
      group than in the untreated group. Infused hAdMSCs were detected in transplanted
      SGs at 4 weeks after irradiation and some cells were found to have differentiated
      into SGCs. In vitro, a low number of co-cultured hAdMSCs (13%-18%) were observed
      to transdifferentiate into SGCs. CONCLUSION: The findings of this study indicate
      that hAdMSCs have the potential to protect against irradiation-induced cell loss
      and to transdifferentiate into SGCs, and suggest that hAdMSC administration
      should be viewed as a candidate therapy for the treatment of radiation-induced SG
      damage.

PMID- 23951101
TI  - Sequential utilization of hosts from different fly families by genetically
      distinct, sympatric populations within the Entomophthora muscae species complex.
AB  - The fungus Entomophthora muscae (Entomophthoromycota, Entomophthorales,
      Entomophthoraceae) is a widespread insect pathogen responsible for fatal
      epizootic events in many dipteran fly hosts. During epizootics in 2011 and 2012
      in Durham, North Carolina, we observed a transition of fungal infections from one
      host, the plant-feeding fly Delia radicum, to a second host, the predatory fly
      Coenosia tigrina. Infections first appeared on Delia in the middle of March, but
      by the end of May, Coenosia comprised 100% of infected hosts. Multilocus sequence
      typing revealed that E. muscae in Durham comprises two distinct subpopulations
      (clades) with several haplotypes in each. Fungi from either clade are able to
      infect both fly species, but vary in their infection phenologies and host
      specificities. Individuals of the more phylogenetically diverse clade I
      predominated during the beginning of the spring epizootic, infecting mostly
      phytophagous Delia flies. Clade II dominated in late April and May and affected
      mostly predatory Coenosia flies. Analysis of population structure revealed two
      subpopulations within E. muscae with limited gene exchange. This study provides
      the first evidence of recombination and population structure within the E. muscae
      species complex, and illustrates the complexity of insect-fungus relationships
      that should be considered for development of biological control methods. 

PMID- 23951099
TI  - The joint effect of hOGG1, APE1, and ADPRT polymorphisms and cooking oil fumes on
      the risk of lung adenocarcinoma in Chinese non-smoking females.
AB  - BACKGROUND: The human 8-oxoguanine DNA glycosylase 1 (hOGG1),
      apurinic/apyrimidinic endonuclease 1 (APE1), and adenosine diphosphate ribosyl
      transferase (ADPRT) genes play an important role in the DNA base excision repair
      pathway. Single nucleotide polymorphisms (SNPs) in critical genes are suspected
      to be associated with the risk of lung cancer. This study aimed to identify the
      association between the polymorphisms of hOGG1 Ser326Cys, APE1 Asp148Glu, and
      ADPRT Val762Ala, and the risk of lung adenocarcinoma in the non-smoking female
      population, and investigated the interaction between genetic polymorphisms and
      environmental exposure in lung adenocarcinoma. METHODS: We performed a hospital
      based case-control study, including 410 lung adenocarcinoma patients and 410
      cancer-free hospital control subjects who were matched for age. Each case and
      control was interviewed to collect information by well-trained interviewers. A
      total of 10 ml of venous blood was collected for genotype testing. Three
      polymorphisms were analyzed by the polymerase chain reaction-restriction fragment
      length polymorphism technique. RESULTS: We found that individuals who were
      homozygous for the variant hOGG1 326Cys/Cys showed a significantly increased risk
      of lung adenocarcinoma (OR = 1.54; 95% CI: 1.01-2.36; P = 0.045). When the
      combined effect of variant alleles was analyzed, we found an increased OR of 1.89
      (95% CI: 1.24-2.88, P = 0.003) for lung adenocarcinoma individuals with more than
      one homozygous variant allele. In stratified analyses, we found that the OR for
      the gene-environment interaction between Ser/Cys and Cys/Cys genotypes of hOGG1
      codon 326 and cooking oil fumes for the risk of lung adenocarcinoma was 1.37 (95%
      CI: 0.77-2.44; P = 0.279) and 2.79 (95% CI: 1.50-5.18; P = 0.001), respectively.
      CONCLUSIONS: The hOGG1 Ser326Cys polymorphism might be associated with the risk
      of lung adenocarcinoma in Chinese non-smoking females. Furthermore, there is a
      significant gene-environment association between cooking oil fumes and hOGG1 326
      Cys/Cys genotype in lung adenocarcinoma among female non-smokers.

PMID- 23951102
TI  - Dizeez: an online game for human gene-disease annotation.
AB  - Structured gene annotations are a foundation upon which many bioinformatics and
      statistical analyses are built. However the structured annotations available in
      public databases are a sparse representation of biological knowledge as a whole.
      The rate of biomedical data generation is such that centralized biocuration
      efforts struggle to keep up. New models for gene annotation need to be explored
      that expand the pace at which we are able to structure biomedical knowledge.
      Recently, online games have emerged as an effective way to recruit, engage and
      organize large numbers of volunteers to help address difficult biological
      challenges. For example, games have been successfully developed for protein
      folding (Foldit), multiple sequence alignment (Phylo) and RNA structure design
      (EteRNA). Here we present Dizeez, a simple online game built with the purpose of
      structuring knowledge of gene-disease associations. Preliminary results from game
      play online and at scientific conferences suggest that Dizeez is producing valid
      gene-disease annotations not yet present in any public database. These early
      results provide a basic proof of principle that online games can be successfully
      applied to the challenge of gene annotation. Dizeez is available at
      http://genegames.org. 

PMID- 23951103
TI  - Assessment of heavy metal contamination in the surrounding soils and surface
      sediments in Xiawangang River, Qingshuitang District.
AB  - Xiawanggang River region is considered to be one of the most polluted areas in
      China due to its huge amount discharge of pollutants and accumulation for years.
      As it is one branch of Xiang River and the area downstream is Changsha city, the
      capital of Hunan Province, the ecological niche of Xiawangang River is very
      important. The pollution treatment in this area was emphasized in the Twelfth
      Five-Year Plan of Chinese government for Xiang River Water Environmental
      Pollution Control. In order to assess the heavy metal pollution and provide the
      base information in this region for The Twelfth Five-Year Plan, contents and
      fractions of four heavy metals (Cd, Cu, Pb and Zn) covering both sediments and
      soils were analyzed to study their contamination state. Three different indexes
      were applied to assess the pollution extent. The results showed this area was
      severely polluted by the four heavy metals, and the total concentrations exceeded
      the Chinese environmental quality standard for soil, grade III, especially for
      Cd. Moreover, Cd, rated as being in high risk, had a high mobility as its great
      contents of exchangeable and carbonates fractions in spite of its relative low
      content. Regression analysis revealed clay could well explain the regression
      equation for Cd, Cu and Zn while pH and sand could significantly interpret the
      regression equation for Pb. Moreover, there was a significant correlation between
      Non-residual fraction and I(geo) for all the four metals. Correlation analysis
      showed four metals maybe had similar pollution sources.

PMID- 23951104
TI  - High concentration of vitamin E decreases thermosensation and thermotaxis
      learning and the underlying mechanisms in the nematode Caenorhabditis elegans.
AB  - alpha-tocopherol is a powerful liposoluble antioxidant and the most abundant
      isoform of vitamin E in the body. Under normal physiological conditions, adverse
      effects of relatively high concentration of vitamin E on organisms and the
      underlying mechanisms are still largely unclear. In the present study, we used
      the nematode Caenorhabditis elegans as an in vivo assay system to investigate the
      possible adverse effects of high concentration of vitamin E on thermosensation
      and thermotaxis learning and the underlying mechanisms. Our data show that
      treatment with 100-200 ug/mL of vitamin E did not noticeably influence both
      thermosensation and thermotaxis learning; however, treatment with 400 ug/mL of
      vitamin E altered both thermosensation and thermotaxis learning. The observed
      decrease in thermotaxis learning in 400 ug/mL of vitamin E treated nematodes
      might be partially due to the moderate but significant deficits in
      thermosensation, but not due to deficits in locomotion behavior or perception to
      food and starvation. Treatment with 400 ug/mL of vitamin E did not noticeably
      influence the morphology of GABAergic neurons, but significantly decreased
      fluorescent intensities of the cell bodies in AFD sensory neurons and AIY
      interneurons, required for thermosensation and thermotaxis learning control.
      Treatment with 400 ug/mL of vitamin E affected presynaptic function of neurons,
      but had no remarkable effects on postsynaptic function. Moreover, promotion of
      synaptic transmission by activating PKC-1 effectively retrieved deficits in both
      thermosensation and thermotaxis learning induced by 400 ug/mL of vitamin E.
      Therefore, relatively high concentrations of vitamin E administration may cause
      adverse effects on thermosensation and thermotaxis learning by inducing damage on
      the development of specific neurons and presynaptic function under normal
      physiological conditions in C. elegans. 

PMID- 23951106
TI  - Let's dance together: synchrony, shared intentionality and cooperation.
AB  - Previous research has shown that the matching of rhythmic behaviour between
      individuals (synchrony) increases cooperation. Such synchrony is most noticeable
      in music, dance and collective rituals. As well as the matching of behaviour,
      such collective performances typically involve shared intentionality: performers
      actively collaborate to produce joint actions. Over three experiments we examined
      the importance of shared intentionality in promoting cooperation from group
      synchrony. Experiment 1 compared a condition in which group synchrony was
      produced through shared intentionality to conditions in which synchrony or
      asynchrony were created as a by-product of hearing the same or different rhythmic
      beats. We found that synchrony combined with shared intentionality produced the
      greatest level of cooperation. To examinef the importance of synchrony when
      shared intentionality is present, Experiment 2 compared a condition in which
      participants deliberately worked together to produce synchrony with a condition
      in which participants deliberately worked together to produce asynchrony. We
      found that synchrony combined with shared intentionality produced the greatest
      level of cooperation. Experiment 3 manipulated both the presence of synchrony and
      shared intentionality and found significantly greater cooperation with synchrony
      and shared intentionality combined. Path analysis supported a reinforcement of
      cooperation model according to which perceiving synchrony when there is a shared
      goal to produce synchrony provides immediate feedback for successful cooperation
      so reinforcing the group's cooperative tendencies. The reinforcement of
      cooperation model helps to explain the evolutionary conservation of traditional
      music and dance performances, and furthermore suggests that the collectivist
      values of such cultures may be an essential part of the mechanisms by which
      synchrony galvanises cooperative behaviours. 

PMID- 23951105
TI  - Weight-bearing locomotion in the developing opossum, Monodelphis domestica
      following spinal transection: remodeling of neuronal circuits caudal to lesion.
AB  - Complete spinal transection in the mature nervous system is typically followed by
      minimal axonal repair, extensive motor paralysis and loss of sensory functions
      caudal to the injury. In contrast, the immature nervous system has greater
      capacity for repair, a phenomenon sometimes called the infant lesion effect. This
      study investigates spinal injuries early in development using the marsupial
      opossum Monodelphis domestica whose young are born very immature, allowing access
      to developmental stages only accessible in utero in eutherian mammals. Spinal
      cords of Monodelphis pups were completely transected in the lower thoracic
      region, T10, on postnatal-day (P)7 or P28 and the animals grew to adulthood. In
      P7-injured animals regrown supraspinal and propriospinal axons through the injury
      site were demonstrated using retrograde axonal labelling. These animals recovered
      near-normal coordinated overground locomotion, but with altered gait
      characteristics including foot placement phase lags. In P28-injured animals no
      axonal regrowth through the injury site could be demonstrated yet they were able
      to perform weight-supporting hindlimb stepping overground and on the treadmill.
      When placed in an environment of reduced sensory feedback (swimming) P7-injured
      animals swam using their hindlimbs, suggesting that the axons that grew across
      the lesion made functional connections; P28-injured animals swam using their
      forelimbs only, suggesting that their overground hindlimb movements were reflex
      dependent and thus likely to be generated locally in the lumbar spinal cord.
      Modifications to propriospinal circuitry in P7- and P28-injured opossums were
      demonstrated by changes in the number of fluorescently labelled neurons detected
      in the lumbar cord following tracer studies and changes in the balance of
      excitatory, inhibitory and neuromodulatory neurotransmitter receptors' gene
      expression shown by qRT-PCR. These results are discussed in the context of
      studies indicating that although following injury the isolated segment of the
      spinal cord retains some capability of rhythmic movement the mechanisms involved
      in weight-bearing locomotion are distinct. 

PMID- 23951107
TI  - Remodeling of hyperpolarization-activated current, Ih, in Ah-type visceral
      ganglion neurons following ovariectomy in adult rats.
AB  - Hyperpolarization-activated currents (Ih) mediated by hyperpolarization-activated
      cyclic nucleotide-gated (HCN) channels modulate excitability of myelinated A- and
      Ah-type visceral ganglion neurons (VGN). Whether alterations in Ih underlie the
      previously reported reduction of excitability of myelinated Ah-type VGNs
      following ovariectomy (OVX) has remained unclear. Here we used the intact nodose
      ganglion preparation in conjunction with electrophysiological approaches to
      examine the role of Ih remodeling in altering Ah-type neuron excitability
      following ovariectomy in adult rats. Ah-type neurons were identified based on
      their afferent conduction velocity. Ah-type neurons in nodose ganglia from non
      OVX rats exhibited a voltage 'sag' as well as 'rebound' action potentials
      immediately following hyperpolarizing current injections, which both were
      suppressed by the Ih blocker ZD7288. Repetitive spike activity induced
      afterhyperpolarizations lasting several hundreds of milliseconds (termed post
      excitatory membrane hyperpolarizations, PEMHs), which were significantly reduced
      by ZD7288, suggesting that they resulted from transient deactivation of Ih during
      the preceding spike trains. Ovariectomy reduced whole-cell Ih density, caused a
      hyperpolarizing shift of the voltage-dependence of Ih activation, and slowed Ih
      activation. OVX-induced Ih remodeling was accompanied by a flattening of the
      stimulus frequency/response curve and loss of PEMHs. Also, HCN1 mRNA levels were
      reduced by ~30% in nodose ganglia from OVX rats compared with their non-OVX
      counterparts. Acute exposure of nodose ganglia to 17beta-estradiol partly
      restored Ih density and accelerated Ih activation in Ah-type cells. In
      conclusion, Ih plays a significant role in modulating the excitability of
      myelinated Ah-type VGNs in adult female rats. 

PMID- 23951108
TI  - Comparison enhances size sensitivity: neural correlates of outcome magnitude
      processing.
AB  - Magnitude is a critical feature of outcomes. In the present study, two event
      related potential (ERP) experiments were implemented to explore the neural
      substrates of outcome magnitude processing. In Experiment 1, we used an adapted
      gambling paradigm where physical area symbols were set to represent potential
      relative outcome magnitudes in order to exclude the possibility that the
      participants would be ignorant of the magnitudes. The context was manipulated as
      total monetary amount: Y4 and Y40. In these two contexts, the relative outcome
      magnitudes were Y1 versus Y3, and Y10 versus Y30, respectively. Experiment 2,
      which provided two area symbols with similar outcome magnitudes, was conducted to
      exclude the possible interpretation of physical area symbol for magnitude effect
      of feedback-related negativity (FRN) in Experiment 1. Our results showed that FRN
      responded to the relative outcome magnitude but not to the context or area
      symbol, with larger amplitudes for relatively small outcomes. A larger FRN effect
      (the difference between losses and wins) was found for relatively large outcomes
      than relatively small outcomes. Relatively large outcomes evoked greater positive
      ERP waves (P300) than relatively small outcomes. Furthermore, relatively large
      outcomes in a high amount context elicited a larger P300 than those in a low
      amount context. The current study indicated that FRN is sensitive to variations
      in magnitude. Moreover, relative magnitude was integrated in both the early and
      late stages of feedback processing, while the monetary amount context was
      processed only in the late stage of feedback processing. 

PMID- 23951109
TI  - The GPVI-Fc fusion protein Revacept reduces thrombus formation and improves
      vascular dysfunction in atherosclerosis without any impact on bleeding times.
AB  - AIMS: Glycoprotein VI (GPVI) is a key platelet receptor which mediates plaque
      induced platelet activation and consecutive atherothrombosis, but GPVI is also
      involved in platelet-mediated atheroprogression. Therefore, interference in GPVI
      mediated platelet activation has the potential to combine short-term and long
      term beneficial effects, specificity and safety especially regarding bleeding
      complications. METHODS AND RESULTS: We investigated the effects of the soluble
      dimeric GPVI receptor fusion protein, Revacept, an antagonist of collagen
      mediated platelet activation, in an animal model of atherosclerosis: twenty week
      old rabbits, which had been fed on a cholesterol-rich diet for 8 weeks, received
      Revacept (8 mg/kg) or control twice weekly for 4 weeks. Pharmacokinetics
      indicated a slight accumulation of the drug in the serum after repeated dosing of
      Revacept for 3 weeks. A significant improvement of endothelial dysfunction after
      0.06 and 0.6 ug/min acetylcholine and a significant decrease of vessel wall
      thickening were found after Revacept treatment. Accordingly, aortic vessel weight
      was reduced, and plaque sizes, macrophage and T-cell invasion tended to be
      reduced in histological evaluations. Bleeding time was determined after tail
      clipping in mice. Revacept alone or in combination with widely used anti-platelet
      drugs revealed a high safety margin with no prolongation of bleeding times.
      CONCLUSION: Repeated doses of Revacept led to a significant improvement of
      endothelial dysfunction and vascular morphology in atherosclerotic rabbits.
      Furthermore, no influence of Revacept on bleeding time alone or in combinations
      with various anti-platelet drugs was found in mice. Thus, the inhibition of
      collagen-mediated platelet interaction with the atherosclerotic endothelium by
      Revacept exerts beneficial effects on morphology and vascular function in vivo
      and seems to have a wide therapeutic window without influencing the bleeding
      time.

PMID- 23951110
TI  - Vertical variation of nonpoint source pollutants in the Three Gorges Reservoir
      Region.
AB  - Nonpoint source (NPS) pollution is considered the main reason for water
      deterioration, but there has been no attempt to incorporate vertical variations
      of NPS pollution into watershed management, especially in mountainous areas. In
      this study, the vertical variations of pollutant yields were explored in the
      Three Gorges Reservoir Region (TGRR) and the relationships between topographic
      attributes and pollutant yields were established. Based on our results, the
      pollutant yields decreased significantly from low altitude to median altitude and
      leveled off rapidly from median altitude to high altitude, indicating logarithmic
      relationships between pollutant yields and altitudes. The pollutant yields peaked
      at an altitude of 200-500 m, where agricultural land and gentle slopes (0-8
      degrees ) are concentrated. Unlike the horizontal distributions, these vertical
      variations were not always related to precipitation patterns but did vary
      obviously with land uses and slopes. This paper also indicates that altitude data
      and proportions of land use could be a reliable estimate of NPS yields at
      different altitudes, with significant implications for land use planning and
      watershed management. 

PMID- 23951111
TI  - Environmental influences on the abundance and sexual composition of white sharks
      Carcharodon carcharias in Gansbaai, South Africa.
AB  - The seasonal occurrence of white sharks visiting Gansbaai, South Africa was
      investigated from 2007 to 2011 using sightings from white shark cage diving
      boats. Generalized linear models were used to investigate the number of great
      white sharks sighted per trip in relation to sex, month, sea surface temperature
      and Multivariate El Nino/Southern Oscillation (ENSO) Indices (MEI). Water
      conditions are more variable in summer than winter due to wind-driven cold water
      upwelling and thermocline displacement, culminating in colder water temperatures,
      and shark sightings of both sexes were higher during the autumn and winter months
      (March-August). MEI, an index to quantify the strength of Southern Oscillation,
      differed in its effect on the recorded numbers of male and female white sharks,
      with highly significant interannual trends. This data suggests that water
      temperature and climatic phenomena influence the abundance of white sharks at
      this coastal site. In this study, more females were seen in Gansbaai overall in
      warmer water/positive MEI years. Conversely, the opposite trend was observed for
      males. In cool water years (2010 to 2011) sightings of male sharks were
      significantly higher than in previous years. The influence of environmental
      factors on the physiology of sharks in terms of their size and sex is discussed.
      The findings of this study could contribute to bather safety programmes because
      the incorporation of environmental parameters into predictive models may help
      identify times and localities of higher risk to bathers and help mitigate human
      white shark interactions. 

PMID- 23951113
TI  - Automatic round-the-clock detection of whales for mitigation from underwater
      noise impacts.
AB  - Loud hydroacoustic sources, such as naval mid-frequency sonars or airguns for
      marine geophysical prospecting, have been increasingly criticized for their
      possible negative effects on marine mammals and were implicated in several whale
      stranding events. Competent authorities now regularly request the implementation
      of mitigation measures, including the shut-down of acoustic sources when marine
      mammals are sighted within a predefined exclusion zone. Commonly, ship-based
      marine mammal observers (MMOs) are employed to visually monitor this zone. This
      approach is personnel-intensive and not applicable during night time, even though
      most hydroacoustic activities run day and night. This study describes and
      evaluates an automatic, ship-based, thermographic whale detection system that
      continuously scans the ship's environs for whale blows. Its performance is
      independent of daylight and exhibits an almost uniform, omnidirectional detection
      probability within a radius of 5 km. It outperforms alerted observers in terms of
      number of detected blows and ship-whale encounters. Our results demonstrate that
      thermal imaging can be used for reliable and continuous marine mammal protection.

PMID- 23951112
TI  - Genetic variation in the base excision repair pathway, environmental risk
      factors, and colorectal adenoma risk.
AB  - Cigarette smoking, high alcohol intake, and low dietary folate levels are risk
      factors for colorectal adenomas. Oxidative damage caused by these three factors
      can be repaired through the base excision repair pathway (BER). We hypothesized
      that genetic variation in BER might modify colorectal adenoma risk. In a
      sigmoidoscopy-based study, we examined associations between 182 haplotype tagging
      SNPs in 14 BER genes, and colorectal adenoma risk, and examined their potential
      role as modifiers of the effect cigarette smoking, alcohol intake, and dietary
      folate levels. Among all individuals, no statistically significant associations
      between BER SNPs and adenoma risk persisted after correction for multiple
      comparisons. However, among Asian-Pacific Islanders we observed two SNPs in FEN1
      and one in NTHL1, and among African-Americans one SNP in APEX1 that were
      associated with colorectal adenoma risk. Significant associations were also
      observed between SNPs in the NEIL2 gene and rectal adenoma risk. Three SNPS
      modified the effect of smoking (MUTYH interaction p = 0.002; OGG1 interaction p =
      0.013); FEN1 interaction p = 0.013)), one SNP in LIG3 modified the effect of
      alcohol consumption (interaction p = 0.024) and two SNPs in LIG3 modified the
      effect of dietary folate (interaction p = 0.001 and p = 0.08) on colorectal
      adenoma risk. These findings support a role for genetic variants in the BER
      pathway as potential modifiers of colorectal adenoma risk. Our findings
      strengthen the role of oxidative damage induced by key lifestyle and dietary risk
      factors in colorectal adenoma formation. 

PMID- 23951114
TI  - Manipulating the sensitivity of signal-induced repression: quantification and
      consequences of altered brinker gradients.
AB  - Traditionally, the analysis of gene regulatory regions suffered from the caveat
      that it was restricted to artificial contexts (e.g. reporter constructs of
      limited size). With the advent of the BAC recombineering technique, genomic
      constructs can now be generated to test regulatory elements in their endogenous
      environment. The expression of the transcriptional repressor brinker (brk) is
      negatively regulated by Dpp signaling. Repression is mediated by small sequence
      motifs, the silencer elements (SEs), that are present in multiple copies in the
      regulatory region of brk. In this work, we manipulated the SEs in the brk locus.
      We precisely quantified the effects of the individual SEs on the Brk gradient in
      the wing disc by employing a 1D data extraction method, followed by the
      quantification of the data with reference to an internal control. We found that
      mutating the SEs results in an expansion of the brk expression domain. However,
      even after mutating all predicted SEs, repression could still be observed in
      regions of maximal Dpp levels. Thus, our data point to the presence of
      additional, low affinity binding sites in the brk locus. 

PMID- 23951115
TI  - HLA-DO as the optimizer of epitope selection for MHC class II antigen
      presentation.
AB  - Processing of antigens for presentation to helper T cells by MHC class II
      involves HLA-DM (DM) and HLA-DO (DO) accessory molecules. A mechanistic
      understanding of DO in this process has been missing. The leading model on its
      function proposes that DO inhibits the effects of DM. To directly study DO
      functions, we designed a recombinant soluble DO and expressed it in insect cells.
      The kinetics of binding and dissociation of several peptides to HLA-DR1 (DR1)
      molecules in the presence of DM and DO were measured. We found that DO reduced
      binding of DR1 to some peptides, and enhanced the binding of some other peptides
      to DR1. Interestingly, these enhancing and reducing effects were observed in the
      presence, or absence, of DM. We found that peptides that were negatively affected
      by DO were DM-sensitive, whereas peptides that were enhanced by DO were DM
      resistant. The positive and negative effects of DO could only be measured on
      binding kinetics as peptide dissociation kinetics were not affected by DO. Using
      Surface Plasmon Resonance, we demonstrate direct binding of DO to a peptide
      receptive, but not a closed conformation of DR1. We propose that DO imposes
      another layer of control on epitope selection during antigen processing. 

PMID- 23951116
TI  - Resistance mutation R292K is induced in influenza A(H6N2) virus by exposure of
      infected mallards to low levels of oseltamivir.
AB  - Resistance to neuraminidase inhibitors (NAIs) is problematic as these drugs
      constitute the major treatment option for severe influenza. Extensive use of the
      NAI oseltamivir (Tamiflu(r)) results in up to 865 ng/L of its active metabolite
      oseltamivir carboxylate (OC) in river water. There one of the natural reservoirs
      of influenza A, dabbling ducks, can be exposed. We previously demonstrated that
      an influenza A(H1N1) virus in mallards (Anas platyrhynchos) exposed to 1 ug/L of
      OC developed oseltamivir resistance through the mutation H274Y (N2-numbering). In
      this study, we assessed the resistance development in an A(H6N2) virus, which
      belongs to the phylogenetic N2 group of neuraminidases with distinct functional
      and resistance characteristics. Mallards were infected with A(H6N2) while exposed
      to 120 ng/L, 1.2 ug/L or 12 ug/L of OC in their sole water source. After 4 days
      with 12 ug/L of OC exposure, the resistance mutation R292K emerged and then
      persisted. Drug sensitivity was decreased ~13,000-fold for OC and ~7.8-fold for
      zanamivir. Viral shedding was similar when comparing R292K and wild-type virus
      indicating sustained replication and transmission. Reduced neuraminidase activity
      and decrease in recovered virus after propagation in embryonated hen eggs was
      observed in R292K viruses. The initial, but not the later R292K isolates reverted
      to wild-type during egg-propagation, suggesting a stabilization of the mutation,
      possibly through additional mutations in the neuraminidase (D113N or D141N) or
      hemagglutinin (E216K). Our results indicate a risk for OC resistance development
      also in a N2 group influenza virus and that exposure to one NAI can result in a
      decreased sensitivity to other NAIs as well. If established in influenza viruses
      circulating among wild birds, the resistance could spread to humans via re
      assortment or direct transmission. This could potentially cause an oseltamivir
      resistant pandemic; a serious health concern as preparedness plans rely heavily
      on oseltamivir before vaccines can be mass-produced. 

PMID- 23951117
TI  - Chemical intolerance among hairdressers in Denmark.
AB  - OBJECTIVES: To investigate the prevalence and the severity of fragrance-related
      symptoms among hairdressers in Denmark compared with the Danish general
      population. Further, to characterize former hairdressers who are severely
      chemically intolerant to fragranced products in relation to sex, age and health-
      and work-related reasons for leaving the hairdressing profession. METHODS: The
      study population consisted of all hairdressers who graduated from the public
      vocational schools in Denmark during 1985 and 2007 (n = 7840) and a random sample
      of individuals from the Danish general population (n = 6000). Both populations
      received a postal questionnaire on symptoms from inhalation of fragranced
      products and the resultant behavioural consequences. All former hairdressers also
      answered additional questions on health- and work-related reasons for leaving the
      profession. RESULTS: No differences were found in the prevalence (OR = 1.0, CI =
      0.89-1.14) or the severity (OR = 1.1, CI = 0.80-1.51) of symptoms from inhalation
      of fragranced products in hairdressers compared with the general population.
      Among hairdressers, however, experience of fragrance-related symptoms (OR = 1.2,
      CI = 1.01-1.31) and adjustments of social (OR = 1.8, CI = 1.12-2.80) and
      occupational conditions (OR = 2.8, CI = 1.84-4.25) were reported significantly
      more often by former hairdressers than current hairdressers. CONCLUSIONS: The
      prevalence and the severity of fragrance-related symptoms were similar in
      hairdressers and the general population. Former hairdressers were more affected
      by fragranced products than current hairdressers were. Although fragrance-related
      symptoms did not seem to be more frequent among hairdressers, the hairdressing
      profession might pose a problem for those who are chemically intolerant.

PMID- 23951118
TI  - Mosquito population regulation and larval source management in heterogeneous
      environments.
AB  - An important question for mosquito population dynamics, mosquito-borne pathogen
      transmission and vector control is how mosquito populations are regulated. Here
      we develop simple models with heterogeneity in egg laying patterns and in the
      responses of larval populations to crowding in aquatic habitats. We use the
      models to evaluate how such heterogeneity affects mosquito population regulation
      and the effects of larval source management (LSM). We revisit the notion of a
      carrying capacity and show how heterogeneity changes our understanding of density
      dependence and the outcome of LSM. Crowding in and productivity of aquatic
      habitats is highly uneven unless egg-laying distributions are fine-tuned to match
      the distribution of habitats' carrying capacities. LSM reduces mosquito
      population density linearly with coverage if adult mosquitoes avoid laying eggs
      in treated habitats, but quadratically if eggs are laid in treated habitats and
      the effort is therefore wasted (i.e., treating 50% of habitat reduces mosquito
      density by approximately 75%). Unsurprisingly, targeting (i.e. treating a subset
      of the most productive pools) gives much larger reductions for similar coverage,
      but with poor targeting, increasing coverage could increase adult mosquito
      population densities if eggs are laid in higher capacity habitats. Our analysis
      suggests that, in some contexts, LSM models that accounts for heterogeneity in
      production of adult mosquitoes provide theoretical support for pursuing mosquito
      borne disease prevention through strategic and repeated application of modern
      larvicides. 

PMID- 23951119
TI  - Reevaluating the role of the hippocampus in delay eyeblink conditioning.
AB  - The role of the hippocampus in delay eyeblink conditioning (DEC) remains
      controversial. Here, we investigated the involvement of the hippocampus in DEC
      with a soft tone as the conditioned stimulus (CS) by using electrolytic lesions
      or muscimol inactivation of guinea pig dorsal hippocampus. Interestingly, when a
      soft tone was used as a CS, electrolytic lesions of the hippocampus significantly
      retarded acquisition of the conditioned response (CR), and muscimol infusions
      into hippocampus distinctly inhibited the acquisition and expression of CR, but
      had no significant effect on consolidation of well-learned CR. In contrast, both
      electrolytic lesions and muscimol inactivation of hippocampus produced no
      significant deficits in the CR when a loud tone was used as the CS. These results
      demonstrate that the hippocampus is essential for the DEC when the delay task was
      rendered more difficult. 

PMID- 23951120
TI  - Economic and environmental impacts of harmful non-indigenous species in southeast
      Asia.
AB  - Harmful non-indigenous species (NIS) impose great economic and environmental
      impacts globally, but little is known about their impacts in Southeast Asia. Lack
      of knowledge of the magnitude of the problem hinders the allocation of
      appropriate resources for NIS prevention and management. We used benefit-cost
      analysis embedded in a Monte-Carlo simulation model and analysed economic and
      environmental impacts of NIS in the region to estimate the total burden of NIS in
      Southeast Asia. The total annual loss caused by NIS to agriculture, human health
      and the environment in Southeast Asia is estimated to be US$33.5 billion (5(th)
      and 95(th) percentile US$25.8-39.8 billion). Losses and costs to the agricultural
      sector are estimated to be nearly 90% of the total (US$23.4-33.9 billion), while
      the annual costs associated with human health and the environment are US$1.85
      billion (US$1.4-2.5 billion) and US$2.1 billion (US$0.9-3.3 billion),
      respectively, although these estimates are based on conservative assumptions. We
      demonstrate that the economic and environmental impacts of NIS in low and middle
      income regions can be considerable and that further measures, such as the
      adoption of regional risk assessment protocols to inform decisions on prevention
      and control of NIS in Southeast Asia, could be beneficial. 

PMID- 23951121
TI  - Response of copepods to elevated pCO2 and environmental copper as co-stressors--a
      multigenerational study.
AB  - We examined the impacts of ocean acidification and copper as co-stressors on the
      reproduction and population level responses of the benthic copepod Tisbe
      battagliai across two generations. Naupliar production, growth, and cuticle
      elemental composition were determined for four pH values: 8.06 (control); 7.95;
      7.82; 7.67, with copper addition to concentrations equivalent to those in benthic
      pore waters. An additive synergistic effect was observed; the decline in naupliar
      production was greater with added copper at decreasing pH than for decreasing pH
      alone. Naupliar production modelled for the two generations revealed a negative
      synergistic impact between ocean acidification and environmentally relevant
      copper concentrations. Conversely, copper addition enhanced copepod growth, with
      larger copepods produced at each pH compared to the impact of pH alone. Copepod
      digests revealed significantly reduced cuticle concentrations of sulphur,
      phosphorus and calcium under decreasing pH; further, copper uptake increased to
      toxic levels that lead to reduced naupliar production. These data suggest that
      ocean acidification will enhance copper bioavailability, resulting in larger, but
      less fecund individuals that may have an overall detrimental outcome for copepod
      populations. 

PMID- 23951122
TI  - Quality of life, activity impairment, and healthcare resource utilization
      associated with atrial fibrillation in the US National Health and Wellness
      Survey.
AB  - OBJECTIVES: This study builds upon current studies of atrial fibrillation (AF)
      and health outcomes by examining more comprehensively the humanistic burden of
      illness (quality of life, activity impairment, and healthcare resource
      utilization) among adult patients with AF, using a large, nationally
      representative sample and matched controls. METHODS: Data were analyzed from the
      Internet-based 2009 US National Health and Wellness Survey. Outcomes were Mental
      and Physical Component Summary (MCS and PCS) and health utility scores from the
      SF-12, activity impairment, hospitalizations, and healthcare provider and
      emergency room (ER) visits. Patients with self-reported diagnosis of AF were
      matched randomly on age and gender with an equal number of respondents without
      AF. Generalized linear models examined outcomes as a function of AF vs. non-AF
      status, controlling for CHADS2 score, comorbidity counts, demographics, and
      clinical variables. Exploratory structural equation modeling assessed the above
      in an integrated model of humanistic burden. RESULTS: Mean age of AF patients
      (1,296 from a total sample of 75,000) was 64.9 years and 65.1% were male.
      Adjusting for covariates, compared with non-AF patients, AF patients had lower
      MCS, PCS, and utility scores, greater activity impairment (rate ratio = 1.26),
      more traditional provider visits (rate ratio = 1.43), and increased odds of ER
      visits (OR = 2.53) and hospitalizations (OR = 2.71). Exploratory structural
      equation modeling analyses revealed that persons with AF experienced a
      significantly higher overall humanistic burden. CONCLUSIONS: This study
      highlights and clarifies the substantial burden of AF and its implications for
      preparing efficacious AF management plans to address the imminent rise in
      prevalence.

PMID- 23951123
TI  - Predictors of three dose on-time compliance with HPV4 vaccination in a
      disadvantaged, underserved, safety net population in the US Midwest.
AB  - BACKGROUND: HPV4 is approved as a series of three timed doses expected to result
      in efficacy against specific HPV infections. Completion rates in the US are quite
      low at the same time the structure of health care delivery is changing. The aim
      of this study was to determine how the patient-, clinic- and systems-level
      characteristics facilitate or hinder the timely completion of three HPV4 doses in
      both adolescent and adult female populations in a high-risk safety net
      population. METHODS: This is a retrospective study in which patient-, clinic- and
      systems-level data are abstracted from the electronic medical record (EMR) for
      all females 10-26 years of age receiving at least one dose of HPV4 between July
      1, 2006 and October 1, 2009. RESULTS: Adults were more likely to complete the
      three dose series if they had at least one health care visit in addition to their
      HPV4 visit, (aOR = 1.54 (95% CI:1.10, 2.15). Adults were less likely to complete
      the three dose series if they received their second HPV4 dose at an acute health
      care, preventive care or postpartum visits compared to an HPV4-only visit (aOR =
      0.31 (95% CI: 0.13, 0.72), 0.12 (0.04, 0.35), 0.30 (0.14, 0.62), respectively).
      Hispanic adults were less likely than whites to complete the series (aOR = 0.24
      (95% CI:0.10, 0.59). 39% of adolescents who completed two doses completed the
      series. CONCLUSIONS: HPV4 is more likely to be effectively administered to adults
      in a safety net population if multiple health care needs can be met within the
      health care system.

PMID- 23951124
TI  - crw1--A novel maize mutant highly susceptible to foliar damage by the western
      corn rootworm beetle.
AB  - Western corn rootworm (WCR), Diabrotica virgifera virgifera LeConte (Coleoptera:
      Chrysomelidae), is the most destructive insect pest of corn (Zea mays L.) in the
      United States. The adult WCR beetles derive their nourishment from multiple
      sources including corn pollen and silks as well as the pollen of alternate hosts.
      Conversely, the corn foliage is largely neglected as a food source by WCR
      beetles, leading to a perception of a passive interaction between the two. We
      report here a novel recessive mutation of corn that was identified and named
      after its foliar susceptibility to corn rootworm beetles (crw1). The crw1 mutant
      under field conditions was exceptionally susceptible to foliar damage by WCR
      beetles in an age-specific manner. It exhibits pleiotropic defects on cell wall
      biochemistry, morphology of leaf epidermal cells and lower structural integrity
      via differential accumulation of cell wall bound phenolic acids. These findings
      indicate that crw1 is perturbed in a pathway that was not previously ascribed to
      WCR susceptibility, as well as implying the presence of an active mechanism(s)
      deterring WCR beetles from devouring corn foliage. The discovery and
      characterization of this mutant provides a unique opportunity for genetic
      analysis of interactions between maize and adult WCR beetles and identify new
      strategies to control the spread and invasion of this destructive pest. 

PMID- 23951125
TI  - Landscape level variation in tick abundance relative to seasonal migration in red
      deer.
AB  - Partial migration is common among northern ungulates, typically involving an
      altitudinal movement for seasonally migratory individuals. The main driving force
      behind migration is the benefit of an extended period of access to newly emerged,
      high quality forage along the green up gradient with increasing altitude; termed
      the forage maturation hypothesis. Any other limiting factor spatially correlated
      with this gradient may provide extra benefits or costs to migration, without
      necessarily being the cause of it. A common ectoparasite on cervids in Europe is
      the sheep tick (Ixodes ricinus), but it has not been tested whether migration may
      lead to the spatial separation from these parasites and thus potentially provide
      an additional benefit to migration. Further, if there is questing of ticks in
      winter ranges in May before spring migration, deer migration may also play a role
      for the distribution of ticks. We quantified the abundance of questing sheep tick
      within winter and summer home ranges of migratory (n=42) and resident red deer
      (Cervus elaphus) individuals (n=32) in two populations in May and August 2009
      2012. Consistent with predictions, there was markedly lower abundance of questing
      ticks in the summer areas of migrating red deer (0.6/20 m(2)), both when compared
      to the annual home range of resident deer (4.9/20 m(2)) and the winter home
      ranges of migrants (5.8/20 m(2)). The reduced abundances within summer home
      ranges of migrants were explained by lower abundance of ticks with increasing
      altitude and distance from the coast. The lower abundance of ticks in summer home
      ranges of migratory deer does not imply that ticks are the main driver of
      migration (being most likely the benefits expected from forage maturation), but
      it suggests that ticks may add to the value of migration in some ecosystems and
      that it may act to spread ticks long distances in the landscape.

PMID- 23951126
TI  - Bound to lose: physical incapacitation increases the conceptualized size of an
      antagonist in men.
AB  - Because decision-making in situations of potential conflict hinges on assessing
      many features of the self and the foe, this process can be facilitated by
      summarizing diverse attributes in a single heuristic representation. Physical
      size and strength are evolutionarily ancient determinants of victory in conflict,
      and their relevance is reinforced during development. Accordingly, size and
      muscularity constitute ready dimensions for a summary representation of relative
      formidability, a perspective paralleled by the notion that social power is
      represented using envisioned relative size. Physical incapacitation constitutes a
      significant tactical disadvantage, hence temporary incapacitation should increase
      the envisioned size and strength of an antagonist. In Study 1, being bound to a
      chair increased men's estimates of the size of an angry man and decreased
      estimates of their own height. Study 2 conceptually replicated these effects:
      among men for whom standing on a balance board was challenging, the attendant
      experience of postural instability increased estimates of an angry man's size and
      muscularity, with similar patterns occurring at a reduced level among all but
      those whose equilibrium was apparently unaffected by this task. 

PMID- 23951127
TI  - Deficiency of retinaldehyde dehydrogenase 1 induces BMP2 and increases bone mass
      in vivo.
AB  - The effects of retinoids, the structural derivatives of vitamin A (retinol), on
      post-natal peak bone density acquisition and skeletal remodeling are complex and
      compartment specific. Emerging data indicates that retinoids, such as all trans
      retinoic acid (ATRA) and its precursor all trans retinaldehyde (Rald), exhibit
      distinct and divergent transcriptional effects in metabolism. Despite these
      observations, the role of enzymes that control retinoid metabolism in bone
      remains undefined. In this study, we examined the skeletal phenotype of mice
      deficient in retinaldehyde dehydrogenase 1 (Aldh1a1), the enzyme responsible for
      converting Rald to ATRA in adult animals. Bone densitometry and micro-computed
      tomography (uCT) demonstrated that Aldh1a1-deficient (Aldh1a1(-/-) ) female mice
      had higher trabecular and cortical bone mass compared to age and sex-matched
      control C57Bl/6 wild type (WT) mice at multiple time points. Histomorphometry
      confirmed increased cortical bone thickness and demonstrated significantly higher
      bone marrow adiposity in Aldh1a1(-/-) mice. In serum assays, Aldh1a1(-/-) mice
      also had higher serum IGF-1 levels. In vitro, primary Aldh1a1(-/-) mesenchymal
      stem cells (MSCs) expressed significantly higher levels of bone morphogenetic
      protein 2 (BMP2) and demonstrated enhanced osteoblastogenesis and adipogenesis
      versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias
      of Aldh1a1(-/-) mice with accompanying induction of BMP2-regulated responses,
      including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation.
      In vitro, Rald, which accumulates in Aldh1a1(-/-) mice, potently induced BMP2 in
      WT MSCs in a retinoic acid receptor (RAR)-dependent manner, suggesting that Rald
      is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo.
      Collectively, these data implicate Aldh1a1 as a novel determinant of cortical
      bone density and marrow adiposity in the skeleton in vivo through modulation of
      BMP signaling. 

PMID- 23951128
TI  - Binding, conformational transition and dimerization of amyloid-beta peptide on
      GM1-containing ternary membrane: insights from molecular dynamics simulation.
AB  - Interactions of amyloid-beta (Abeta) with neuronal membrane are associated with
      the progression of Alzheimer's disease (AD). Ganglioside GM1 has been shown to
      promote the structural conversion of Abeta and increase the rate of peptide
      aggregation; but the exact nature of interaction driving theses processes remains
      to be explored. In this work, we have carried out atomistic-scale computer
      simulations (totaling 2.65 us) to investigate the behavior of Abeta monomer and
      dimers in GM1-containing raft-like membrane. The oligosaccharide head-group of
      GM1 was observed to act as scaffold for Abeta-binding through sugar-specific
      interactions. Starting from the initial helical peptide conformation, a beta
      hairpin motif was formed at the C-terminus of the GM1-bound Abeta-monomer; that
      didn't appear in absence of GM1 (both in fluid POPC and liquid-ordered
      cholesterol/POPC bilayers and also in aqueous medium) within the simulation time
      span. For Abeta-dimers, the beta-structure was further enhanced by peptide
      peptide interactions, which might influence the propensity of Abeta to aggregate
      into higher-ordered structures. The salt-bridges and inter-peptide hydrogen bonds
      were found to account for dimer stability. We observed spontaneous formation of
      intra-peptide D(23)-K(28) salt-bridge and a turn at V(24)GSN(27) region - long
      been accepted as characteristic structural-motifs for amyloid self-assembly.
      Altogether, our results provide atomistic details of Abeta-GM1 and Abeta-Abeta
      interactions and demonstrate their importance in the early-stages of GM1-mediated
      Abeta-oligomerisation on membrane surface. 

PMID- 23951129
TI  - Pyrosequencing to identify homogeneous phenomenon when using recipients/donors
      with different CYP3A5*3 genotypes in living donor liver transplantation.
AB  - This study used pyrosequencing to determine the proportional distribution of
      CYP3A5*3 genotypes to further confirm the homogeneous phenomenon that is observed
      when recipients and donors in living donor liver transplantation (LDLT) have a
      different single nucleotide polymorphism (SNP) genotype. We enrolled 42
      recipient/living donor pairs and the SNPs of CYP3A5*3 were identified by
      polymerase chain reaction-restriction fragment length polymorphism. We performed
      120 liver graft biopsies as part of clinical investigations after LDLT.
      Pyrosequencing of the CYP3A5*3 SNPs revealed that among the 16 recipients with
      the G/G genotype, 94.68% had the G and 5.32% the A allele. Among the 14
      recipients with the A/G genotype, 78.08% had the G and 21.92% the A allele, and
      among the 12 recipients with the A/A genotype, 18.45% had the G and 81.55% the A
      allele. Among the 12 donors with the G/G genotype, 93.85% had the G and 6.14% the
      A allele. Among the 26 donors with the A/G genotype, 75.73% had the G and 24.27%
      the A allele, and among the 4 donors with the A/A genotype, 11.09% had the G and
      88.91% the A allele. There were a total of 120 liver graft biopsy samples; among
      the 37 recipients with the G/G genotype, 89.74% had the G and 10.26% the A
      allele, among the 70 recipients with the A/G genotype, 71.57% had the G and
      28.43% the A allele, and among the 13 recipients with the A/A genotype, 48.25%
      had the G and 51.75% the A allele. The proportional distribution of G and A
      alleles of the CYP3A5*3 SNP between recipients/donors and liver grafts after LDLT
      was significantly different (p<0.001). Pyrosequencing was useful in identifying
      detailed proportional changes of the CYP3A5*3 SNP allele distribution, and to
      confirm the homogeneous phenomenon when recipients and donors in LDLT have a
      different genotype. 

PMID- 23951131
TI  - Systematic review and meta-analysis of therapeutic hypothermia in animal models
      of spinal cord injury.
AB  - BACKGROUND: Therapeutic hypothermia is a clinically useful neuroprotective
      therapy for cardiac arrest and neonatal hypoxic ischemic encephalopathy and may
      potentially be useful for the treatment of other neurological conditions
      including traumatic spinal cord injury (SCI). The pre-clinical studies evaluating
      the effectiveness of hypothermia in acute SCI broadly utilise either systemic
      hypothermia or cooling regional to the site of injury. The literature has not
      been uniformly positive with conflicting studies of varying quality, some
      performed decades previously. METHODS: In this study, we systematically review
      and meta-analyse the literature to determine the efficacy of systemic and
      regional hypothermia in traumatic SCI, the experimental conditions influencing
      this efficacy, and the influence of study quality on outcome. Three databases
      were utilised; PubMed, ISI Web of Science and Embase. Our inclusion criteria
      consisted of the (i) reporting of efficacy of hypothermia on functional outcome
      (ii) number of animals and (iii) mean outcome and variance in each group.
      RESULTS: Systemic hypothermia improved behavioural outcomes by 24.5% (95% CI 10.2
      to 38.8) and a similar magnitude of improvement was seen across a number of high
      quality studies. The overall behavioural improvement with regional hypothermia
      was 26.2%, but the variance was wide (95% CI -3.77 to 56.2). This result may
      reflect a preponderance of positive low quality data, although a preferential
      effect of hypothermia in ischaemic models of injury may explain some of the
      disparate data. Sufficient heterogeneity was present between studies of regional
      hypothermia to reveal a number of factors potentially influencing efficacy,
      including depth and duration of hypothermia, animal species, and neurobehavioural
      assessment. However, these factors could reflect the influence of earlier lower
      quality literature. CONCLUSION: Systemic hypothermia appears to be a promising
      potential method of treating acute SCI on the basis of meta-analysis of the pre
      clinical literature and the results of high quality animal studies.

PMID- 23951130
TI  - Rhinovirus 3C protease facilitates specific nucleoporin cleavage and
      mislocalisation of nuclear proteins in infected host cells.
AB  - Human Rhinovirus (HRV) infection results in shut down of essential cellular
      processes, in part through disruption of nucleocytoplasmic transport by cleavage
      of the nucleoporin proteins (Nups) that make up the host cell nuclear pore.
      Although the HRV genome encodes two proteases (2A and 3C) able to cleave host
      proteins such as Nup62, little is known regarding the specific contribution of
      each. Here we use transfected as well as HRV-infected cells to establish for the
      first time that 3C protease is most likely the mediator of cleavage of Nup153
      during HRV infection, while Nup62 and Nup98 are likely to be targets of HRV2A
      protease. HRV16 3C protease was also able to elicit changes in the appearance and
      distribution of the nuclear speckle protein SC35 in transfected cells,
      implicating it as a key mediator of the mislocalisation of SC35 in HRV16-infected
      cells. In addition, 3C protease activity led to the redistribution of the
      nucleolin protein out of the nucleolus, but did not affect nuclear localisation
      of hnRNP proteins, implying that complete disruption of nucleocytoplasmic
      transport leading to relocalisation of hnRNP proteins from the nucleus to the
      cytoplasm in HRV-infected cells almost certainly requires 2A in addition to 3C
      protease. Thus, a specific role for HRV 3C protease in cleavage and
      mislocalisation of host cell nuclear proteins, in concert with 2A, is implicated
      for the first time in HRV pathogenesis. 

PMID- 23951132
TI  - Osterix-cre labeled progenitor cells contribute to the formation and maintenance
      of the bone marrow stroma.
AB  - We have carried out fate mapping studies using Osterix-EGFPCre and Osterix-CreERt
      animal models and found Cre reporter expression in many different cell types that
      make up the bone marrow stroma. Constitutive fate mapping resulted in the
      labeling of different cellular components located throughout the bone marrow,
      whereas temporal fate mapping at E14.5 resulted in the labeling of cells within a
      region of the bone marrow. The identity of cell types marked by constitutive and
      temporal fate mapping included osteoblasts, adipocytes, vascular smooth muscle,
      perineural, and stromal cells. Prolonged tracing of embryonic precursors labeled
      at E14.5dpc revealed the continued existence of their progeny up to 10 months of
      age, suggesting that fate mapped, labeled embryonic precursors gave rise to long
      lived bone marrow progenitor cells. To provide further evidence for the marking
      of bone marrow progenitors, bone marrow cultures derived from Osterix-EGFPCre/Ai9
      mice showed that stromal cells retained Cre reporter expression and yielded a
      FACS sorted population that was able to differentiate into osteoblasts,
      adipocytes, and chondrocytes in vitro and into osteoblasts, adipocytes, and
      perivascular stromal cells after transplantation. Collectively, our studies
      reveal the developmental process by which Osterix-Cre labeled embryonic
      progenitors give rise to adult bone marrow progenitors which establish and
      maintain the bone marrow stroma. 

PMID- 23951134
TI  - Interacting epidemics and coinfection on contact networks.
AB  - The spread of certain diseases can be promoted, in some cases substantially, by
      prior infection with another disease. One example is that of HIV, whose
      immunosuppressant effects significantly increase the chances of infection with
      other pathogens. Such coinfection processes, when combined with nontrivial
      structure in the contact networks over which diseases spread, can lead to complex
      patterns of epidemiological behavior. Here we consider a mathematical model of
      two diseases spreading through a single population, where infection with one
      disease is dependent on prior infection with the other. We solve exactly for the
      sizes of the outbreaks of both diseases in the limit of large population size,
      along with the complete phase diagram of the system. Among other things, we use
      our model to demonstrate how diseases can be controlled not only by reducing the
      rate of their spread, but also by reducing the spread of other infections upon
      which they depend. 

PMID- 23951133
TI  - IFN-epsilon is constitutively expressed by cells of the reproductive tract and is
      inefficiently secreted by fibroblasts and cell lines.
AB  - Type-I interferons (IFNs) form a large family of cytokines that primarily act to
      control the early development of viral infections. Typical type-I IFN genes, such
      as those encoding IFN-alpha or IFN-beta are upregulated by viral infection in
      many cell types. In contrast, the gene encoding IFN-epsilon was reported to be
      constitutively expressed by cells of the female reproductive tract and to
      contribute to the protection against vaginal infections with herpes simplex virus
      2 and Chlamydia muridarum. Our data confirm the lack of induction of IFN-epsilon
      expression after viral infection and the constitutive expression of IFN-epsilon
      by cells of the female but also of the male reproductive organs. Interestingly,
      when expressed from transfected expression plasmids in 293T, HeLa or Neuro2A
      cells, the mouse and human IFN-epsilon precursors were inefficiently processed
      and secretion of IFN-epsilon was minimal. Analysis of chimeric constructs
      produced between IFN-epsilon and limitin (IFN-zeta) showed that both the signal
      peptide and the mature moiety of IFN-epsilon contribute to poor processing of the
      precursor. Immunofluorescent detection of FLAG-tagged IFN-epsilon in transfected
      cells suggested that IFN-epsilon and chimeric proteins were defective for
      progression through the secretory pathway. IFN-epsilon did not, however, act
      intracellularly and impart an antiviral state to producing cells. Given the
      constitutive expression of IFN-epsilon in specialized cells and the poor
      processing of IFN-epsilon precursor in fibroblasts and cell lines, we hypothesize
      that IFN-epsilon secretion may require a co-factor specifically expressed in
      cells of the reproductive organs, that might secure the system against aberrant
      release of this IFN. 

PMID- 23951135
TI  - Bicistronic DNA vaccines simultaneously encoding HIV, HSV and HPV antigens
      promote CD8+ T cell responses and protective immunity.
AB  - Millions of people worldwide are currently infected with human papillomavirus
      (HPV), herpes simplex virus (HSV) or human immunodeficiency virus (HIV). For this
      enormous contingent of people, the search for preventive and therapeutic
      immunological approaches represents a hope for the eradication of latent
      infection and/or virus-associated cancer. To date, attempts to develop vaccines
      against these viruses have been mainly based on a monovalent concept, in which
      one or more antigens of a virus are incorporated into a vaccine formulation. In
      the present report, we designed and tested an immunization strategy based on DNA
      vaccines that simultaneously encode antigens for HIV, HSV and HPV. With this
      purpose in mind, we tested two bicistronic DNA vaccines (pIRES I and pIRES II)
      that encode the HPV-16 oncoprotein E7 and the HIV protein p24 both genetically
      fused to the HSV-1 gD envelope protein. Mice i.m. immunized with the DNA vaccines
      mounted antigen-specific CD8+ T cell responses, including in vivo cytotoxic
      responses, against the three antigens. Under experimental conditions, the
      vaccines conferred protective immunity against challenges with a vaccinia virus
      expressing the HIV-derived protein Gag, an HSV-1 virus strain and implantation of
      tumor cells expressing the HPV-16 oncoproteins. Altogether, our results show that
      the concept of a trivalent HIV, HSV, and HPV vaccine capable to induce CD8+ T
      cell-dependent responses is feasible and may aid in the development of preventive
      and/or therapeutic approaches for the control of diseases associated with these
      viruses.

PMID- 23951136
TI  - Loss of control increases belief in precognition and belief in precognition
      increases control.
AB  - Every year thousands of dollars are spent on psychics who claim to "know" the
      future. The present research questions why, despite no evidence that humans are
      able to psychically predict the future, do people persist in holding irrational
      beliefs about precognition? We argue that believing the future is predictable
      increases one's own perceived ability to exert control over future events. As a
      result, belief in precognition should be particularly strong when people most
      desire control-that is, when they lack it. In Experiment 1 (N = 87), people who
      were experimentally induced to feel low in control reported greater belief in
      precognition than people who felt high in control. Experiment 2 (N = 53)
      investigated whether belief in precognition increases perceived control.
      Consistent with this notion, providing scientific evidence that precognition is
      possible increased feelings of control relative to providing scientific evidence
      that precognition was not possible. Experiment 3 (N = 132) revealed that when
      control is low, believing in precognition helps people to feel in control once
      more. Prediction therefore acts as a compensatory mechanism in times of low
      control. The present research provides new insights into the psychological
      functions of seemingly irrational beliefs, like belief in psychic abilities.

PMID- 23951137
TI  - Xanthine oxidase mediates axonal and myelin loss in a murine model of multiple
      sclerosis.
AB  - OBJECTIVES: Oxidative stress plays an important role in the pathogenesis of
      multiple sclerosis (MS). Though reactive oxygen species (ROS) are produced by
      various mechanisms, xanthine oxidase (XO) is a major enzyme generating ROS in the
      context of inflammation. The objectives of this study were to investigate the
      involvement of XO in the pathogenesis of MS and to develop a potent new therapy
      for MS based on the inhibition of ROS. METHODS: XO were assessed in a model of
      MS: experimental autoimmune encephalomyelitis (EAE). The contribution of XO
      generated ROS to the pathogenesis of EAE was assessed by treating EAE mice with a
      novel XO inhibitor, febuxostat. The efficacy of febuxostat was also examined in
      in vitro studies. RESULTS: We showed for the first time that the expression and
      the activity of XO were increased dramatically within the central nervous system
      of EAE mice as compared to naive mice. Furthermore, prophylactic administration
      of febuxostat, a XO inhibitor, markedly reduced the clinical signs of EAE. Both
      in vivo and in vitro studies showed infiltrating macrophages and microglia as the
      major sources of excess XO production, and febuxostat significantly suppressed
      ROS generation from these cells. Inflammatory cellular infiltration and glial
      activation in the spinal cord of EAE mice were inhibited by the treatment with
      febuxostat. Importantly, therapeutic efficacy was observed not only in mice with
      relapsing-remitting EAE but also in mice with secondary progressive EAE by
      preventing axonal loss and demyelination. CONCLUSION: These results highlight the
      implication of XO in EAE pathogenesis and suggest XO as a target for MS treatment
      and febuxostat as a promising therapeutic option for MS neuropathology.

PMID- 23951138
TI  - Interleukin-10 inhibits lipopolysaccharide induced miR-155 precursor stability
      and maturation.
AB  - The anti-inflammatory cytokine interleukin-10 (IL-10) is essential for
      attenuating the inflammatory response, which includes reducing the expression of
      pro-inflammatory microRNA-155 (miR-155) in lipopolysaccharide (LPS) activated
      macrophages. miR-155 enhances the expression of pro-inflammatory cytokines such
      as TNFalpha and suppresses expression of anti-inflammatory molecules such as
      SOCS1. Therefore, we examined the mechanism by which IL-10 inhibits miR-155. We
      found that IL-10 treatment did not affect the transcription of the miR-155 host
      gene nor the nuclear export of pre-miR-155, but rather destabilized both pri-miR
      155 and pre-miR-155 transcripts, as well as interfered with the final maturation
      of miR-155. This inhibitory effect of IL-10 on miR-155 expression involved the
      contribution of both the STAT3 transcription factor and the phosphoinositol
      phosphatase SHIP1. This is the first report showing evidence that IL-10 regulates
      miRNA expression post-transcriptionally. 

PMID- 23951139
TI  - An in silico analysis of the binding modes and binding affinities of small
      molecule modulators of PDZ-peptide interactions.
AB  - Inhibitors of PDZ-peptide interactions have important implications in a variety
      of biological processes including treatment of cancer and Parkinson's disease.
      Even though experimental studies have reported characterization of peptidomimetic
      inhibitors of PDZ-peptide interactions, the binding modes for most of them have
      not been characterized by structural studies. In this study we have attempted to
      understand the structural basis of the small molecule-PDZ interactions by in
      silico analysis of the binding modes and binding affinities of a set of 38 small
      molecules with known K(i) or K(d) values for PDZ2 and PDZ3 domains of PSD-95
      protein. These two PDZ domains show differential selectivity for these compounds
      despite having a high degree of sequence similarity and almost identical peptide
      binding pockets. Optimum binding modes for these ligands for PDZ2 and PDZ3
      domains were identified by using a novel combination of semi-flexible docking and
      explicit solvent molecular dynamics (MD) simulations. Analysis of the binding
      modes revealed most of the peptidomimectic ligands which had high K(i) or K(d)
      moved away from the peptide binding pocket, while ligands with high binding
      affinities remained in the peptide binding pocket. The differential specificities
      of the PDZ2 and PDZ3 domains primarily arise from differences in the conformation
      of the loop connecting betaB and betaC strands, because this loop interacts with
      the N-terminal chemical moieties of the ligands. We have also computed the
      MM/PBSA binding free energy values for these 38 compounds with both the PDZ
      domains from multiple 5 ns MD trajectories on each complex i.e. a total of 228 MD
      trajectories of 5 ns length each. Interestingly, computational binding free
      energies show good agreement with experimental binding free energies with a
      correlation coefficient of approximately 0.6. Thus our study demonstrates that
      combined use of docking and MD simulations can help in identification of potent
      inhibitors of PDZ-peptide complexes.

PMID- 23951140
TI  - Impairment of IFN-gamma response to synthetic peptides of Mycobacterium
      tuberculosis in a 7-day whole blood assay.
AB  - Studies on Mycobacterium tuberculosis (MTB) antigens are of interest in order to
      improve vaccine efficacy and to define biomarkers for diagnosis and treatment
      monitoring. The methodologies used for these investigations differ greatly
      between laboratories and discordant results are common. The IFN-gamma response to
      two well characterized MTB antigens ESAT-6 and CFP-10, in the form of recombinant
      proteins and synthetic peptides, was evaluated in HIV-1 uninfected persons in
      both long-term (7 day) and 24 hour, commercially available QuantiFERON TB Gold in
      Tube (QFT-GIT), whole blood assays. Our findings showed differences in the IFN
      gamma response between 24 hour and 7 day cultures, with recombinant proteins
      inducing a significantly higher response than the peptide pools in 7 day whole
      blood assays. The activity of peptides and recombinant proteins did not differ in
      24 hour whole blood or peripheral blood mononuclear cell (PBMC) based assays, nor
      in the ELISpot assay. Further analysis by SELDI-TOF mass spectrometry showed that
      the peptides are degraded over the course of 7 days of incubation in whole blood
      whilst the recombinant proteins remain intact. This study therefore demonstrates
      that screening antigenic candidates as synthetic peptides in long-term whole
      blood assays may underestimate immunogenicity. 

PMID- 23951141
TI  - Lateral diffusion of nutrients by mammalian herbivores in terrestrial ecosystems.
AB  - Animals translocate nutrients by consuming nutrients at one point and excreting
      them or dying at another location. Such lateral fluxes may be an important
      mechanism of nutrient supply in many ecosystems, but lack quantification and a
      systematic theoretical framework for their evaluation. This paper presents a
      mathematical framework for quantifying such fluxes in the context of mammalian
      herbivores. We develop an expression for lateral diffusion of a nutrient, where
      the diffusivity is a biologically determined parameter depending on the
      characteristics of mammals occupying the domain, including size-dependent
      phenomena such as day range, metabolic demand, food passage time, and population
      size. Three findings stand out: (a) Scaling law-derived estimates of diffusion
      parameters are comparable to estimates calculated from estimates of each
      coefficient gathered from primary literature. (b) The diffusion term due to
      transport of nutrients in dung is orders of magnitude large than the coefficient
      representing nutrients in bodymass. (c) The scaling coefficients show that large
      herbivores make a disproportionate contribution to lateral nutrient transfer. We
      apply the diffusion equation to a case study of Kruger National Park to estimate
      the conditions under which mammal-driven nutrient transport is comparable in
      magnitude to other (abiotic) nutrient fluxes (inputs and losses). Finally, a
      global analysis of mammalian herbivore transport is presented, using a
      comprehensive database of contemporary animal distributions. We show that
      continents vary greatly in terms of the importance of animal-driven nutrient
      fluxes, and also that perturbations to nutrient cycles are potentially quite
      large if threatened large herbivores are driven to extinction. 

PMID- 23951142
TI  - Evaluating Alzheimer's disease progression using rate of regional hippocampal
      atrophy.
AB  - Alzheimer's disease (AD) is characterized by neurofibrillary tangle and neuropil
      thread deposition, which ultimately results in neuronal loss. A large number of
      magnetic resonance imaging studies have reported a smaller hippocampus in AD
      patients as compared to healthy elderlies. Even though this difference is often
      interpreted as atrophy, it is only an indirect measurement. A more direct way of
      measuring the atrophy is to use repeated MRIs within the same individual. Even
      though several groups have used this appropriate approach, the pattern of
      hippocampal atrophy still remains unclear and difficult to relate to underlying
      pathophysiology. Here, in this longitudinal study, we aimed to map hippocampal
      atrophy rates in patients with AD, mild cognitive impairment (MCI) and elderly
      controls. Data consisted of two MRI scans for each subject. The symmetric
      deformation field between the first and the second MRI was computed and mapped
      onto the three-dimensional hippocampal surface. The pattern of atrophy rate was
      similar in all three groups, but the rate was significantly higher in patients
      with AD than in control subjects. We also found higher atrophy rates in
      progressive MCI patients as compared to stable MCI, particularly in the antero
      lateral portion of the right hippocampus. Importantly, the regions showing the
      highest atrophy rate correspond to those that were described to have the highest
      burden of tau deposition. Our results show that local hippocampal atrophy rate is
      a reliable biomarker of disease stage and progression and could also be
      considered as a method to objectively evaluate treatment effects. 

PMID- 23951143
TI  - Mapping ERbeta genomic binding sites reveals unique genomic features and
      identifies EBF1 as an ERbeta interactor.
AB  - Considerable effort by numerous laboratories has resulted in an improved
      understanding of estrogen and SERM action mediated by the two estrogen receptors,
      ERalpha and ERbeta. However, many of the targets for ERbeta in cell physiology
      remain elusive. Here, the C4-12/Flag.ERbeta cell line which stably expressed
      Flag.ERbeta is used to study ERbeta genomic functions without ERalpha
      interference. Mapping ERbeta binding sites in these cells reveals ERbeta unique
      distribution and motif enrichment patterns. Accompanying our mapping results,
      nascent RNA profiling is performed on cells at the same treatment time. The
      combined results allow the identification of ERbeta target genes. Gene ontology
      analysis reveals that ERbeta targets are enriched in differentiation, development
      and apoptosis. Concurrently, E2 treatment suppresses proliferation in these
      cells. Within ERbeta binding sites, while the most prevalent binding motif is the
      canonical ERE, motifs of known ER interactors are also enriched in ERbeta binding
      sites. Moreover, among enriched binding motifs are those of GFI, REST and EBF1,
      which are unique to ERbeta binding sites in these cells. Further characterization
      confirms the association between EBF1 and the estrogen receptors, which favors
      the N-terminal region of the receptor. Furthermore, EBF1 negatively regulates ERs
      at the protein level. In summary, by studying ERbeta genomic functions in our
      cell model, we confirm the anti-proliferative role of ERbeta and discover the
      novel cross talk of ERbeta with EBF1 which has various implications in normal
      physiology. 

PMID- 23951144
TI  - Climate influences fledgling sex ratio and sex-specific dispersal in a seabird.
AB  - Climate influences the dynamics of natural populations by direct effects over
      habitat quality but also modulating the phenotypic responses of organisms' life
      history traits. These responses may be different in males and females,
      particularly in dimorphic species, due to sex-specific requirements or
      constraints. Here, in a coastal seabird, the European shag (Phalacrocorax
      aristotelis), we studied the influence of climate (North Atlantic Oscillation,
      NAO; Sea Surface Temperature, SST) on two sex-related population parameters:
      fledgling sex ratio and sex-specific dispersal. We found that fledgling sex ratio
      was female skewed in NAO-positive years and male skewed in NAO-negative years.
      Accordingly, females dispersed a longer distance in NAO-positive years when
      females were overproduced, and on the contrary, males dispersed more in NAO
      negative years. Overall, our findings provide rare evidence on vertebrates with
      genetic sex determination that climate conditions may govern population dynamics
      by affecting sex-specific density and dispersal. 

PMID- 23951145
TI  - Metabolic response of Candida albicans to phenylethyl alcohol under hyphae
      inducing conditions.
AB  - Phenylethyl alcohol was one of the first quorum sensing molecules (QSMs)
      identified in C. albicans. This extracellular signalling molecule inhibits the
      hyphal formation of C. albicans at high cell density. Little is known, however,
      about the underlying mechanisms by which this QSM regulates the morphological
      switches of C. albicans. Therefore, we have applied metabolomics and isotope
      labelling experiments to investigate the metabolic changes that occur in C.
      albicans in response to phenylethyl alcohol under defined hyphae-inducing
      conditions. Our results showed a global upregulation of central carbon metabolism
      when hyphal development was suppressed by phenylethyl alcohol. By comparing the
      metabolic changes in response to phenylethyl alcohol to our previous metabolomic
      studies, we were able to short-list 7 metabolic pathways from central carbon
      metabolism that appear to be associated with C. albicans morphogenesis.
      Furthermore, isotope-labelling data showed that phenylethyl alcohol is indeed
      taken up and catabolised by yeast cells. Isotope-labelled carbon atoms were found
      in the majority of amino acids as well as in lactate and glyoxylate. However,
      isotope-labelled carbon atoms from phenylethyl alcohol accumulated mainly in the
      pyridine ring of NAD(+)/NADH and NADP(-/)NADPH molecules, showing that these
      nucleotides were the main products of phenylethyl alcohol catabolism.
      Interestingly, two metabolic pathways where these nucleotides play an important
      role, nitrogen metabolism and nicotinate/nicotinamide metabolism, were also short
      listed through our previous metabolomics works as metabolic pathways likely to be
      closely associated with C. albicans morphogenesis. 

PMID- 23951146
TI  - Familiarity bias and physiological responses in contagious yawning by dogs
      support link to empathy.
AB  - In humans, the susceptibility to yawn contagion has been theoretically and
      empirically related to our capacity for empathy. Because of its relevance to
      evolutionary biology, this phenomenon has been the focus of recent investigations
      in non-human species. In line with the empathic hypothesis, contagious yawning
      has been shown to correlate with the level of social attachment in several
      primate species. Domestic dogs (Canis familiaris) have also shown the ability to
      yawn contagiously. To date, however, the social modulation of dog contagious
      yawning has received contradictory support and alternative explanations (i.e.,
      yawn as a mild distress response) could explain positive evidence. The present
      study aims to replicate contagious yawning in dogs and to discriminate between
      the two possible mediating mechanisms (i.e., empathic vs. distress related
      response). Twenty-five dogs observed familiar (dog's owner) and unfamiliar human
      models (experimenter) acting out a yawn or control mouth movements. Concurrent
      physiological measures (heart rate) were additionally monitored for twenty-one of
      the subjects. The occurrence of yawn contagion was significantly higher during
      the yawning condition than during the control mouth movements. Furthermore, the
      dogs yawned more frequently when watching the familiar model than the unfamiliar
      one demonstrating that the contagiousness of yawning in dogs correlated with the
      level of emotional proximity. Moreover, subjects' heart rate did not differ among
      conditions suggesting that the phenomenon of contagious yawning in dogs is
      unrelated to stressful events. Our findings are consistent with the view that
      contagious yawning is modulated by affective components of the behavior and may
      indicate that rudimentary forms of empathy could be present in domesticated dogs.

PMID- 23951147
TI  - Trained eyes: experience promotes adaptive gaze control in dynamic and uncertain
      visual environments.
AB  - Current eye-tracking research suggests that our eyes make anticipatory movements
      to a location that is relevant for a forthcoming task. Moreover, there is
      evidence to suggest that with more practice anticipatory gaze control can
      improve. However, these findings are largely limited to situations where
      participants are actively engaged in a task. We ask: does experience modulate
      anticipative gaze control while passively observing a visual scene? To tackle
      this we tested people with varying degrees of experience of tennis, in order to
      uncover potential associations between experience and eye movement behaviour
      while they watched tennis videos. The number, size, and accuracy of saccades
      (rapid eye-movements) made around 'events,' which is critical for the scene
      context (i.e. hit and bounce) were analysed. Overall, we found that experience
      improved anticipatory eye-movements while watching tennis clips. In general,
      those with extensive experience showed greater accuracy of saccades to upcoming
      event locations; this was particularly prevalent for events in the scene that
      carried high uncertainty (i.e. ball bounces). The results indicate that, even
      when passively observing, our gaze control system utilizes prior relevant
      knowledge in order to anticipate upcoming uncertain event locations. 

PMID- 23951148
TI  - Enhanced susceptibility to spontaneous seizures of noda epileptic rats by loss of
      synaptic zn(2+).
AB  - Zinc homeostasis in the brain is associated with the etiology and manifestation
      of epileptic seizures. Adult Noda epileptic rats (NER, >12-week-old) exhibit
      spontaneously generalized tonic-clonic convulsion about once a day. To pursue the
      involvement of synaptic Zn(2+) signal in susceptibility to spontaneous seizures,
      in the present study, the effect of zinc chelators on epileptogenesis was
      examined using adult NER. Clioquinol (CQ) and TPEN are lipophilic zinc chelotors,
      transported into the brain and reduce the levels of synaptic Zn(2+). The
      incidence of tonic-clonic convulsion was markedly increased after i.p. injection
      of CQ (30-100 mg/kg) and TPEN (1 mg/kg). The basal levels of extracellular Zn(2+)
      measured by ZnAF-2 were decreased before tonic-clonic convulsion was induced with
      zinc chelators. The hippocampal electroencephalograms during CQ (30 mg/kg)
      induced convulsions were similar to those during sound-induced convulsions in NER
      reported previously. Exocytosis of hippocampal mossy fibers, which was measured
      with FM4-64, was significantly increased in hippocampal slices from CQ-injected
      NER that did not show tonic-clonic convulsion yet. These results indicate that
      the abnormal excitability of mossy fibers is induced prior to epileptic seizures
      by injection of zinc chelators into NER. The incidence of tonic-clonic convulsion
      induced with CQ (30 mg/kg) was significantly reduced by co-injection with
      aminooxyacetic acid (5-10 mg/kg), an anticonvulsant drug enhancing GABAergic
      activity, which did not affect locomotor activity. The present paper demonstrates
      that the abnormal excitability in the brain, especially in mossy fibers, which is
      potentially associated with the insufficient GABAergic neuron activity, may be a
      factor to reduce the threshold for epileptogenesis in NER. 

PMID- 23951149
TI  - HLA-DRB1 shared epitope-dependent DR-DQ haplotypes are associated with both anti
      CCP-positive and -negative rheumatoid arthritis in Chinese Han.
AB  - The association between Human Leukocyte Antigen (HLA) class II and rheumatoid
      arthritis (RA) has been extensively studied, but few reported DR-DQ haplotype.
      Here we investigated the association of HLA-DRB1, DQA1, DQB1, and DR-DQ
      haplotypes with RA susceptibility and with anti-CCP antibodies in 281 RA patients
      and 297 control in Han population. High-resolution genotyping were performed. The
      HLA-DRB1 shared epitope (SE)-encoding allele *0405 displayed the most significant
      RA association (P = 1.35*10(-6)). The grouped DRB1 SE alleles showed great
      association with RA (P = 3.88*10(-13)). The DRB1 DRRAA alleles displayed
      significant protective effects (P = 0.021). The SE-dependent DR-DQ haplotype SE
      DQ3/4/5 remained strong association with both anti-CCP -positive (P = 3.71*10(
      13)) and -negative RA (P = 3.89*10(-5)). Our study revealed that SE alleles and
      its haplotypes SE-DQ3/4/5 were highly associated with RA susceptibility in Han
      population. The SE-DQ3/4/5 haplotypes were associated with both anti-CCP positive
      RA and -negative RA. 

PMID- 23951150
TI  - Human umbilical cord matrix stem cells maintain multilineage differentiation
      abilities and do not transform during long-term culture.
AB  - Umbilical cord matrix stem cells (UCMSC) have generated great interest in various
      therapeutic approaches, including liver regeneration. This article aims to
      analyze the specific characteristics and the potential occurrence of premalignant
      alterations of UCMSC during long-term expansion, which are important issues for
      clinical applications. UCMSC were isolated from the umbilical cord of 14 full
      term newborns and expanded in vitro until senescence. We examined the long-term
      growth potential, senescence characteristics, immunophenotype and multilineage
      differentiation capacity of these cells. In addition, their genetic stability was
      assessed through karyotyping, telomerase maintenance mechanisms and analysis of
      expression and functionality of cell cycle regulation genes. The tumorigenic
      potential was also studied in immunocompromised mice. In vitro, UCMSC reached up
      to 33.7 +/- 2.1 cumulative population doublings before entering replicative
      senescence. Their immunophenotype and differentiation potential, notably into
      hepatocyte-like cells, remained stable over time. Cytogenetic analyses did not
      reveal any chromosomal abnormality and the expression of oncogenes was not
      induced. Telomere maintenance mechanisms were not activated. Just as UCMSC lacked
      transformed features in vitro, they could not give rise to tumors in vivo. UCMSC
      could be expanded in long-term cultures while maintaining stable genetic features
      and endodermal differentiation potential. UCMSC therefore represent safe
      candidates for liver regenerative medicine.

PMID- 23951151
TI  - Correlation between human leukocyte antigen class II alleles and HAI titers
      detected post-influenza vaccination.
AB  - Influenza is a major cause of morbidity and mortality. Despite vaccination, many
      elderly recipients do not develop a protective antibody response. To determine
      whether Human Leukocyte Antigen (HLA) alleles modulate seroprotection to
      influenza, a cohort of HLA class II-typed high-risk vaccine recipients was
      investigated. Haemagglutinin inhibition (HAI) titres were measured 14-40 days
      post-subunit vaccination. Seroprotection was defined as HAI titres reaching 40 or
      greater for all three vaccine strains. HLA-DRB1*04?01 and HLA-DPB1*04?01 alleles
      were detected at higher frequencies in seroprotected compared with non
      seroprotected individuals. Thus, the presence of certain HLA class II alleles may
      determine the magnitude of antibody responses to influenza vaccination.

PMID- 23951152
TI  - Structural dynamics of human telomeric G-quadruplex loops studied by molecular
      dynamics simulations.
AB  - Loops which are linkers connecting G-strands and supporting the G-tetrad core in
      G-quadruplex are important for biological roles of G-quadruplexes. TTA loop is a
      common sequence which mainly resides in human telomeric DNA (hTel) G-quadruplex.
      A series of molecular dynamics (MD) simulations were carried out to investigate
      the structural dynamics of TTA loops. We found that (1) the TA base pair formed
      in TTA loops are very stable, the occupied of all hydrogen bonds are more than
      0.95. (2) The TA base pair makes the adjacent G-quartet more stable than others.
      (3) For the edgewise loop and the diagonal loop, most loop bases are stacking
      with others, only few bases have considerable freedom. (4) The stabilities of
      these stacking structures are distinct. Part of the loops, especially TA base
      pairs, and bases stacking with the G-quartet, maintain certain stable
      conformations in the simulation, but other parts, like TT and TA stacking
      structures, are not stable enough. For the first time, spontaneous conformational
      switches of TTA edgewise loops were observed in our long time MD simulations. (5)
      For double chain reversal loop, it is really hard to maintain a stable
      conformation in the long time simulation under present force fields (parm99 and
      parmbsc0), as it has multiple conformations with similar free energies. 

PMID- 23951153
TI  - Sexually transmitted infections among heterosexual male clients of female sex
      workers in China: a systematic review and meta-analysis.
AB  - BACKGROUND: Female sex workers have been the target of numerous sexually
      transmitted infection (STI) prevention strategies in China, but their male
      clients have attracted considerably less public health attention and resources.
      We sought to systematically assess the prevalence of HIV, syphilis, gonorrhea,
      and chlamydia among heterosexual male clients of female sex workers in China.
      METHODS/PRINCIPAL FINDINGS: Original research manuscripts were identified by
      searching Chinese and English language databases, and 37 studies analyzing 26,552
      male clients were included in the review. Client STI prevalence across studies
      was heterogeneous. Pooled prevalence estimates and 95% confidence intervals were
      0.68% (0.36-1.28%) for HIV, 2.91% (2.17-3.89%) for syphilis, 2.16% (1.46-3.17%)
      for gonorrhea, and 8.01% (4.94-12.72%) for chlamydia. CONCLUSIONS/SIGNIFICANCE:
      The pooled prevalence estimates of HIV, syphilis, gonorrhea, and chlamydia among
      clients in this review exceed the prevalences previously reported among
      population-representative samples and low-risk groups in China. However,
      heterogeneity across studies and sampling limitations prevent definitive
      conclusions about how the prevalence of STIs in this population compares to the
      general population. These findings suggest a need for greater attention to
      clients' sexual risk and disease prevalence in China's STI research agenda in
      order to inform effective prevention policies.

PMID- 23951154
TI  - Variability in exposure of epitope G40-R43 of domain i in commercial anti-beta2
      glycoprotein I IgG ELISAs.
AB  - BACKGROUND: A major problem for diagnosing the antiphospholipid syndrome (APS) is
      the high variability between commercial anti-beta2glycoprotein I (beta2GPI)
      assays. Predominantly antibodies reactive against cryptic epitope Glycine40
      Arginine43 (G40-R43) in domain I are associated with an increased risk for
      thrombosis. Upon interaction with anionic surfaces beta2GPI opens up, thereby
      exposing G40-R43. OBJECTIVES: To examine whether suboptimal exposure of epitope
      G40-R43 explains the variations in results observed between commercial assays.
      METHODS: Two patient-derived monoclonal antibodies were tested on neutral versus
      anionic plates. Antibody P1-117 reacts with G40-R43 in the open conformation
      while P2-6 recognizes beta2GPI irrespective of its conformation. These antibodies
      were tested in commercial anti-beta2GPI assays (A-E). RESULTS: In assay A, both
      antibodies showed equal reactivity towards beta2GPI, indicating that all the
      beta2GPI exposes G40-R43. In other assays P1-117 displayed lower reactivity than
      P2-6, demonstrating reduced G40-R43 availability. To exclude influences of other
      assay features, reactivity was re-examined on plates of assay A and B using the
      protocol/reagents from each assay. In all combinations, reactivity of both
      antibodies on a plate was comparable to results obtained with its own
      protocol/reagents, suggesting that the coating, rather than other assay
      components, accounts for the observed differences. In two patient cohorts we
      demonstrated that a number of domain I-reactive samples are missed in assays
      characterized by a decreased exposure of epitope G40-R43. CONCLUSIONS: Exposure
      of epitope G40-R43 on beta2GPI is highly variable between commercial anti
      beta2GPI assays. As a consequence, patients can be falsely assigned negative in
      assays characterized by a reduced exposure of G40-R43.

PMID- 23951155
TI  - Tonic-clonic activity at subarachnoid hemorrhage onset: impact on complications
      and outcome.
AB  - OBJECTIVE: Tonic-clonic activity (TCA) at onset complicates 3% to 21% of cases of
      subarachnoid hemorrhage (SAH). The impact of onset TCA on in-hospital
      complications, including seizures, remains unclear. One study associated onset
      TCA with poor clinical outcome at 6 weeks after SAH, but to our knowledge no
      other studies have confirmed this relationship. This study aims to assess the
      impact of onset TCA on in-hospital complications, poor functional outcome,
      mortality, and epilepsy at 3 months. METHODS: Analysis of a prospective study
      cohort of 1479 SAH patients admitted to Columbia University Medical Center
      between 1996 and 2012. TCA within 6 hours of hemorrhage onset was identified
      based on accounts of emergency care providers or family witnesses. RESULTS: TCA
      at onset was described in 170 patients (11%). Patients with onset TCA were
      younger (P = 0.002), presented more often with poor clinical grade (55% vs. 26%,
      P<0.001) and had larger amounts of cisternal, intraventricular, and intracerebral
      blood than those without onset TCA (all, P<0.001). After adjusting for known
      confounders, onset TCA was significantly associated with in-hospital seizures (OR
      3.80, 95%-CI: 2.43-5.96, P<0.001), in-hospital pneumonia (OR 1.56, 95%-CI: 1.06
      2.31, p = 0.02), and delayed cerebral ischemia (OR 1.77, 95%-CI: 1.21-2.58, P =
      0.003). At 3 months, however, onset TCA was not associated with poor functional
      outcome, mortality, and epilepsy after adjusting for age, admission clinical
      grade, and cisternal blood volume. CONCLUSIONS: Onset TCA is not a rare event as
      it complicates 11% of cases of SAH. New and clinically relevant findings are the
      association of onset TCA with in-hospital seizures, pneumonia and delayed
      cerebral ischemia. Despite the increased risk of in-hospital complications, onset
      TCA is not associated with disability, mortality, and epilepsy at 3 months.

PMID- 23951156
TI  - Inflammatory response to fine particulate air pollution exposure: neutrophil
      versus monocyte.
AB  - OBJECTIVES: Studies have shown that chronic exposure to ambient fine particulate
      matter (less than 2.5 um in aerodynamic diameter, PM2.5) pollution induces
      insulin resistance through alterations in inflammatory pathways. It is critical
      to study how the immune system responds to this stimulant, which has been linked
      to cardiovascular and autoimmune diseases, but few studies have been focused on
      such involvement of both neutrophils and monocytes in a timely manner. We
      hypothesized that the neutrophil was involved in the inflammatory response to air
      pollution. METHODS AND RESULTS: C57BL/6 mice were exposed to PM2.5 or filtered
      air (6 hours/day, 5 days/week) for 5, 14, and 21 days, respectively, in Columbus,
      OH. At the end of each of the exposure periods, we investigated the inflammatory
      response through flow cytometry, histology, intravital microscopy, and real-time
      PCR. PM2.5-exposed mice demonstrated a significant inflammatory response after 5
      days of exposure. In the lung tissue and bronchoalveolar lavage fluid,
      monocytes/macrophages showed a transient response, while neutrophils showed a
      cumulative response. In addition, exposure to PM2.5 resulted in elevation of the
      monocyte chemoattractant protein 1 (MCP-1) cytokine, a monocyte/macrophage
      attractant in blood, at an early stage of exposure. CONCLUSIONS: These findings
      suggest that PM2.5 exposure induces the inflammatory responses from both
      macrophages and neutrophils involvement.

PMID- 23951157
TI  - Light-intensity physical activity and cardiometabolic biomarkers in US
      adolescents.
AB  - BACKGROUND: The minimal physical activity intensity that would confer health
      benefits among adolescents is unknown. The purpose of this study was to examine
      the associations of accelerometer-derived light-intensity (split into low and
      high) physical activity, and moderate- to vigorous-intensity physical activity
      with cardiometabolic biomarkers in a large population-based sample. METHODS: The
      study is based on 1,731 adolescents, aged 12-19 years from the 2003/04 and
      2005/06 National Health and Nutrition Examination Survey. Low light-intensity
      activity (100-799 counts/min), high light-intensity activity (800 counts/min to
      <4 METs) and moderate- to vigorous-intensity activity (>= 4 METs, Freedson age
      specific equation) were accelerometer-derived. Cardiometabolic biomarkers,
      including waist circumference, systolic blood pressure, diastolic blood pressure,
      HDL-cholesterol, and C-reactive protein were measured. Triglycerides, LDL-
      cholesterol, insulin, glucose, and homeostatic model assessments of beta-cell
      function (HOMA-%B) and insulin sensitivity (HOMA-%S) were also measured in a
      fasting sub-sample (n=807). RESULTS: Adjusted for confounders, each additional
      hour/day of low light-intensity activity was associated with 0.59 (95% CI: 1.18
      0.01) mmHG lower diastolic blood pressure. Each additional hour/day of high light
      intensity activity was associated with 1.67 (2.94-0.39) mmHG lower diastolic
      blood pressure and 0.04 (0.001-0.07) mmol/L higher HDL-cholesterol. Each
      additional hour/day of moderate- to vigorous-intensity activity was associated
      with 3.54 (5.73-1.35) mmHG lower systolic blood pressure, 5.49 (1.11-9.77)% lower
      waist circumference, 25.87 (6.08-49.34)% lower insulin, and 16.18 (4.92-28.53)%
      higher HOMA-%S. CONCLUSIONS: Time spent in low light-intensity physical activity
      and high light-intensity physical activity had some favorable associations with
      biomarkers. Consistent with current physical activity recommendations for
      adolescents, moderate- to vigorous-intensity activity had favorable associations
      with many cardiometabolic biomarkers. While increasing MVPA should still be a
      public health priority, further studies are needed to identify dose-response
      relationships for light-intensity activity thresholds to inform future
      recommendations and interventions for adolescents.

PMID- 23951158
TI  - FmMDb: a versatile database of foxtail millet markers for millets and bioenergy
      grasses research.
AB  - The prominent attributes of foxtail millet (Setaria italica L.) including its
      small genome size, short life cycle, inbreeding nature, and phylogenetic
      proximity to various biofuel crops have made this crop an excellent model system
      to investigate various aspects of architectural, evolutionary and physiological
      significances in Panicoid bioenergy grasses. After release of its whole genome
      sequence, large-scale genomic resources in terms of molecular markers were
      generated for the improvement of both foxtail millet and its related species.
      Hence it is now essential to congregate, curate and make available these genomic
      resources for the benefit of researchers and breeders working towards crop
      improvement. In view of this, we have constructed the Foxtail millet Marker
      Database (FmMDb; http://www.nipgr.res.in/foxtail.html), a comprehensive online
      database for information retrieval, visualization and management of large-scale
      marker datasets with unrestricted public access. FmMDb is the first database
      which provides complete marker information to the plant science community
      attempting to produce elite cultivars of millet and bioenergy grass species, thus
      addressing global food insecurity. 

PMID- 23951159
TI  - A comprehensive insight into binding of hippuric acid to human serum albumin: a
      study to uncover its impaired elimination through hemodialysis.
AB  - Binding of hippuric acid (HA), a uremic toxin, with human serum albumin (HSA) has
      been examined by isothermal titration calorimetry (ITC), differential scanning
      calorimetry (DSC), molecular docking, circular dichroism (CD) and fluorescence
      spectroscopy to understand the reason that govern its impaired elimination
      through hemodialysis. ITC results shows that the HA binds with HSA at high (K b
      ~10(4)) and low affinity (K b ~10(3)) sites whereas spectroscopic results predict
      binding at a single site (K b~10(3)). The HA form complex with HSA that involves
      electrostatic, hydrogen and hydrophobic binding forces as illustrated by
      calculated thermodynamic parameters. Molecular docking and displacement studies
      collectively revealed that HA bound to both site I and site II; however,
      relatively strongly to the later. Esterase-like activity of HSA confirms the
      involvement of Arg410 and Tyr411 of Sudlow site II in binding of HA. CD results
      show slight conformational changes occurs in the protein upon ligation that may
      be responsible for the discrepancy in van't Hoff and calorimetric enthalpy
      change. Furthermore, an increase in T(1)(m) and T(2)(m) is observed from DSC
      results that indicate increase in stability of HSA upon binding to HA. The
      combined results provide that HA binds to HSA and thus its elimination is
      hindered.

PMID- 23951160
TI  - Possible role of mother-daughter vocal interactions on the development of species
      specific song in gibbons.
AB  - Mother-infant vocal interactions play a crucial role in the development of human
      language. However, comparatively little is known about the maternal role during
      vocal development in nonhuman primates. Here, we report the first evidence of
      mother-daughter vocal interactions contributing to vocal development in gibbons,
      a singing and monogamous ape species. Gibbons are well known for their species
      specific duets sung between mates, yet little is known about the role of
      intergenerational duets in gibbon song development. We observed singing
      interactions between free-ranging mothers and their sub-adult daughters prior to
      emigration. Daughters sang simultaneously with their mothers at different rates.
      First, we observed significant acoustic variation between daughters. Co-singing
      rates between mother and daughter were negatively correlated with the temporal
      precision of the song's synchronization. In addition, songs of daughters who co
      sang less with their mothers were acoustically more similar to the maternal song
      than any other adult female's song. All variables have been reported to be
      influenced by social relationships of pairs. Therefore those correlations would
      be mediated by mother-daughter social relationship, which would be modifiable in
      daughter's development. Here we hypothesized that daughters who co-sing less
      often, well-synchronize, and converge acoustically with the maternal acoustic
      pattern would be at a more advanced stage of social independence in sub-adult
      females prior to emigration. Second, we observed acoustic matching between
      mothers and daughters when co-singing, suggesting short-term vocal flexibility.
      Third, we found that mothers adjusted songs to a more stereotyped pattern when co
      singing than when singing alone. This vocal adjustment was stronger for mothers
      with daughters who co-sang less. These results indicate the presence of socially
      mediated vocal flexibility in gibbon sub-adults and adults, and that mother
      daughter co-singing interactions may enhance vocal development. More comparative
      work, notably longitudinal and experimental, is now needed to clarify maternal
      roles during song development. 

PMID- 23951162
TI  - Characterization and evolution of conserved MicroRNA through duplication events
      in date palm (Phoenix dactylifera).
AB  - MicroRNAs (miRNAs) are important regulators of gene expression at the post
      transcriptional level in a wide range of species. Highly conserved miRNAs
      regulate ancestral transcription factors common to all plants, and control
      important basic processes such as cell division and meristem function. We
      selected 21 conserved miRNA families to analyze the distribution and maintenance
      of miRNAs. Recently, the first genome sequence in Palmaceae was released: date
      palm (Phoenix dactylifera). We conducted a systematic miRNA analysis in date
      palm, computationally identifying and characterizing the distribution and
      duplication of conserved miRNAs in this species compared to other published plant
      genomes. A total of 81 miRNAs belonging to 18 miRNA families were identified in
      date palm. The majority of miRNAs in date palm and seven other well-studied plant
      species were located in intergenic regions and located 4 to 5 kb away from the
      nearest protein-coding genes. Sequence comparison showed that 67% of date palm
      miRNA members were present in duplicated segments, and that 135 pairs of miRNA
      containing segments were duplicated in Arabidopsis, tomato, orange, rice, apple,
      poplar and soybean with a high similarity of non coding sequences between
      duplicated segments, indicating genomic duplication was a major force for
      expansion of conserved miRNAs. Duplicated miRNA pairs in date palm showed
      divergence in pre-miRNA sequence and in number of promoters, implying that these
      duplicated pairs may have undergone divergent evolution. Comparisons between date
      palm and the seven other plant species for the gain/loss of miR167 loci in an
      ancient segment shared between monocots and dicots suggested that these conserved
      miRNAs were highly influenced by and diverged as a result of genomic duplication
      events. 

PMID- 23951161
TI  - Loss of ACE2 exacerbates murine renal ischemia-reperfusion injury.
AB  - Ischemia-reperfusion (I/R) is a model of acute kidney injury (AKI) that is
      characterized by vasoconstriction, oxidative stress, apoptosis and inflammation.
      Previous studies have shown that activation of the renin-angiotensin system (RAS)
      may contribute to these processes. Angiotensin converting enzyme 2 (ACE2)
      metabolizes angiotensin II (Ang II) to angiotensin-(1-7), and recent studies
      support a beneficial role for ACE2 in models of chronic kidney disease. However,
      the role of ACE2 in models of AKI has not been fully elucidated. In order to test
      the hypothesis that ACE2 plays a protective role in AKI we assessed I/R injury in
      wild-type (WT) mice and ACE2 knock-out (ACE2 KO) mice. ACE2 KO and WT mice
      exhibited similar histologic injury scores and measures of kidney function at 48
      hours after reperfusion. Loss of ACE2 was associated with increased neutrophil,
      macrophage, and T cell infiltration in the kidney. mRNA levels for pro
      inflammatory cytokines, interleukin-1beta, interleukin-6 and tumour necrosis
      factor-alpha, as well as chemokines macrophage inflammatory protein 2 and
      monocyte chemoattractant protein-1, were increased in ACE2 KO mice compared to WT
      mice. Changes in inflammatory cell infiltrates and cytokine expression were also
      associated with greater apoptosis and oxidative stress in ACE2 KO mice compared
      to WT mice. These data demonstrate a protective effect of ACE2 in I/R AKI. 

PMID- 23951163
TI  - cAMP level modulates scleral collagen remodeling, a critical step in the
      development of myopia.
AB  - The development of myopia is associated with decreased ocular scleral collagen
      synthesis in humans and animal models. Collagen synthesis is, in part, under the
      influence of cyclic adenosine monophosphate (cAMP). We investigated the
      associations between cAMP, myopia development in guinea pigs, and collagen
      synthesis by human scleral fibroblasts (HSFs). Form-deprived myopia (FDM) was
      induced by unilateral masking of guinea pig eyes. Scleral cAMP levels increased
      selectively in the FDM eyes and returned to normal levels after unmasking and
      recovery. Unilateral subconjunctival treatment with the adenylyl cyclase (AC)
      activator forskolin resulted in a myopic shift accompanied by reduced collagen
      mRNA levels, but it did not affect retinal electroretinograms. The AC inhibitor
      SQ22536 attenuated the progression of FDM. Moreover, forskolin inhibited collagen
      mRNA levels and collagen secretion by HSFs. The inhibition was reversed by
      SQ22536. These results demonstrate a critical role of cAMP in control of myopia
      development. Selective regulation of cAMP to control scleral collagen synthesis
      may be a novel therapeutic strategy for preventing and treating myopia. 

PMID- 23951164
TI  - Airborne detection and quantification of swine influenza a virus in air samples
      collected inside, outside and downwind from swine barns.
AB  - Airborne transmission of influenza A virus (IAV) in swine is speculated to be an
      important route of virus dissemination, but data are scarce. This study attempted
      to detect and quantify airborne IAV by virus isolation and RRT-PCR in air samples
      collected under field conditions. This was accomplished by collecting air samples
      from four acutely infected pig farms and locating air samplers inside the barns,
      at the external exhaust fans and downwind from the farms at distances up to 2.1
      km. IAV was detected in air samples collected in 3 out of 4 farms included in the
      study. Isolation of IAV was possible from air samples collected inside the barn
      at two of the farms and in one farm from the exhausted air. Between 13% and 100%
      of samples collected inside the barns tested RRT-PCR positive with an average
      viral load of 3.20E+05 IAV RNA copies/m3 of air. Percentage of exhaust positive
      air samples also ranged between 13% and 100% with an average viral load of
      1.79E+04 RNA copies/m3 of air. Influenza virus RNA was detected in air samples
      collected between 1.5 and 2.1 Km away from the farms with viral levels
      significantly lower at 4.65E+03 RNA copies/m3. H1N1, H1N2 and H3N2 subtypes were
      detected in the air samples and the hemagglutinin gene sequences identified in
      the swine samples matched those in aerosols providing evidence that the viruses
      detected in the aerosols originated from the pigs in the farms under study.
      Overall our results indicate that pigs can be a source of IAV infectious aerosols
      and that these aerosols can be exhausted from pig barns and be transported
      downwind. The results from this study provide evidence of the risk of aerosol
      transmission in pigs under field conditions.

PMID- 23951165
TI  - EphA2-induced angiogenesis in ewing sarcoma cells works through bFGF production
      and is dependent on caveolin-1.
AB  - Angiogenesis is the result of the combined activity of the tumor microenvironment
      and signaling molecules. The angiogenic switch is represented as an imbalance
      between pro- and anti-angiogenic factors and is a rate-limiting step in the
      development of tumors. Eph receptor tyrosine kinases and their membrane-anchored
      ligands, known as ephrins, constitute the largest receptor tyrosine kinase (RTK)
      subfamily and are considered a major family of pro-angiogenic RTKs. Ewing sarcoma
      (EWS) is a highly aggressive bone and soft tissue tumor affecting children and
      young adults. As other solid tumors, EWS are reliant on a functional vascular
      network for the delivery of nutrients and oxygen and for the removal of waste.
      Based on the biological roles of EphA2 in promoting angiogenesis, we explored the
      functional role of this receptor and its relationship with caveolin-1 (CAV1) in
      EWS angiogenesis. We demonstrated that lack of CAV1 results in a significant
      reduction in micro vascular density (MVD) on 3 different in vivo models. In
      vitro, this phenomenon correlated with inactivation of EphA2 receptor, lack of
      AKT response and downregulation of bFGF. We also demonstrated that secreted bFGF
      from EWS cells acted as chemoattractant for endothelial cells. Furthermore,
      interaction between EphA2 and CAV1 was necessary for the right localization and
      signaling of the receptor to produce bFGF through AKT and promote migration of
      endothelial cells. Finally, introduction of a dominant-negative form of EphA2
      into EWS cells mostly reproduced the effects occurred by CAV1 silencing, strongly
      suggesting that the axis EphA2-CAV1 participates in the promotion of endothelial
      cell migration toward the tumors favoring EWS angiogenesis. 

PMID- 23951166
TI  - CRY2 genetic variants associate with dysthymia.
AB  - People with mood disorders often have disruptions in their circadian rhythms.
      Recent molecular genetics has linked circadian clock genes to mood disorders. Our
      objective was to study two core circadian clock genes, CRY1 and CRY2 as well as
      TTC1 that interacts with CRY2, in relation to depressive and anxiety disorders.
      Of these three genes, 48 single-nucleotide polymorphisms (SNPs) whose selection
      was based on the linkage disequilibrium and potential functionality were
      genotyped in 5910 individuals from a nationwide population-based sample. The
      diagnoses of major depressive disorder, dysthymia and anxiety disorders were
      assessed with a structured interview (M-CIDI). In addition, the participants
      filled in self-report questionnaires on depressive and anxiety symptoms. Logistic
      and linear regression models were used to analyze the associations of the SNPs
      with the phenotypes. Four CRY2 genetic variants (rs10838524, rs7121611,
      rs7945565, rs1401419) associated significantly with dysthymia (false discovery
      rate q<0.05). This finding together with earlier CRY2 associations with winter
      depression and with bipolar type 1 disorder supports the view that CRY2 gene has
      a role in mood disorders. 

PMID- 23951167
TI  - Structures of Streptococcus pneumoniae PiaA and its complex with ferrichrome
      reveal insights into the substrate binding and release of high affinity iron
      transporters.
AB  - Iron scarcity is one of the nutrition limitations that the Gram-positive
      infectious pathogens Streptococcus pneumoniae encounter in the human host. To
      guarantee sufficient iron supply, the ATP binding cassette (ABC) transporter Pia
      is employed to uptake iron chelated by hydroxamate siderophore, via the membrane
      anchored substrate-binding protein PiaA. The high affinity towards ferrichrome
      enables PiaA to capture iron at a very low concentration in the host. We
      presented here the crystal structures of PiaA in both apo and ferrichrome
      complexed forms at 2.7 and 2.1 A resolution, respectively. Similar to other class
      III substrate binding proteins, PiaA is composed of an N-terminal and a C
      terminal domain bridged by an alpha-helix. At the inter-domain cleft, a molecule
      of ferrichrome is stabilized by a number of highly conserved residues. Upon
      ferrichrome binding, two highly flexible segments at the entrance of the cleft
      undergo significant conformational changes, indicating their contribution to the
      binding and/or release of ferrichrome. Superposition to the structure of
      Escherichia coli ABC transporter BtuF enabled us to define two conserved
      residues: Glu119 and Glu262, which were proposed to form salt bridges with two
      arginines of the permease subunits. Further structure-based sequence alignment
      revealed that the ferrichrome binding pattern is highly conserved in a series of
      PiaA homologs encoded by both Gram-positive and negative bacteria, which were
      predicted to be sensitive to albomycin, a sideromycin antibiotic derived from
      ferrichrome. 

PMID- 23951168
TI  - Sonic hedgehog-induced histone deacetylase activation is required for cerebellar
      granule precursor hyperplasia in medulloblastoma.
AB  - Medulloblastoma, the most common pediatric brain tumor, is thought to arise from
      deregulated proliferation of cerebellar granule precursor (CGP) cells. Sonic
      hedgehog (Shh) is the primary mitogen that regulates proliferation of CGP cells
      during the early stages of postnatal cerebellum development. Aberrant activation
      of Shh signaling during this time has been associated with hyperplasia of CGP
      cells and eventually may lead to the development of medulloblastoma. The
      molecular targets of Shh signaling involved in medulloblastoma formation are
      still not well-understood. Here, we show that Shh regulates sustained activation
      of histone deacetylases (HDACs) and that this activity is required for continued
      proliferation of CGP cells. Suppression of HDAC activity not only blocked the Shh
      induced CGP proliferation in primary cell cultures, but also ameliorated aberrant
      CGP proliferation at the external germinal layer (EGL) in a medulloblastoma mouse
      model. Increased levels of mRNA and protein of several HDAC family members were
      found in medulloblastoma compared to wild type cerebellum suggesting that HDAC
      activity is required for the survival/progression of tumor cells. The
      identification of a role of HDACs in the early steps of medulloblastoma formation
      suggests there may be a therapeutic potential for HDAC inhibitors in this
      disease. 

PMID- 23951169
TI  - Anti-dsDNA antibody isotypes in systemic lupus erythematosus: IgA in addition to
      IgG anti-dsDNA help to identify glomerulonephritis and active disease.
AB  - OBJECTIVES: To evaluate the role of serum IgG, IgM and IgA anti-dsDNA antibody
      isotypes in the diagnosis of systemic lupus erythematosus (SLE), and their
      association with clinical features and disease activity, in a large cohort of SLE
      patients. METHODS: Sera of 200 SLE patients (mean age 34+/-10.3 years; 26 male
      and 174 female; median duration of disease 115 months, range 7-378), and of 206
      controls, including 19 Sjogren's syndrome, 27 rheumatoid arthritis, 26 psoriatic
      arthritis, 15 idiopathic inflammatory myopathies (IIM), 13 systemic sclerosis, 49
      infectious diseases and 57 healthy subjects, were tested for anti-dsDNA IgG, IgM
      and IgA isotypes. RESULTS: Selecting a cutoff corresponding to 95% specificity,
      the sensitivity of IgG, IgM and IgA anti-dsDNA antibodies in SLE was 55%, 30% and
      49%, respectively; 12.5%, 1% and 7.5% of SLE patients had positive IgG, IgM or
      IgA isotype alone, respectively. SLE patients with glomerulonephritis showed
      higher levels of IgA anti-dsDNA (p = 0.0002), anti-dsDNA IgG/IgM (p = 0.001) and
      IgA/IgM (p<0.0001) ratios than patients without renal disease. No significant
      associations have been found between anti-dsDNA isotypes and other clinical
      features. IgA anti-dsDNA (p = 0.01) (but not IgG or IgM) and IgG/IgM ratio (p =
      0.005) were significantly higher in patients with more active disease (ECLAM
      score >4). CONCLUSIONS: The detection of IgA anti-dsDNA autoantibodies seems to
      improve our ability to diagnose SLE and to define lupus nephritis phenotype and
      active disease. By contrast, IgM anti-dsDNA antibodies might be protective for
      renal involvement. These data support the hypothesis that anti-dsDNA antibody
      class clustering may help to refine SLE diagnosis and prognosis.

PMID- 23951170
TI  - Smoking in asthma is associated with elevated levels of corticosteroid resistant
      sputum cytokines-an exploratory study.
AB  - BACKGROUND: Current cigarette smoking is associated with reduced acute responses
      to corticosteroids and worse clinical outcomes in stable chronic asthma. The
      mechanism by which current smoking promotes this altered behavior is currently
      unclear. Whilst cytokines can induce corticosteroid insensitivity in-vitro, how
      current and former smoking affects airway cytokine concentrations and their
      responses to oral corticosteroids in stable chronic asthma is unclear.
      OBJECTIVES: To examine blood and sputum cytokine concentrations in never, ex and
      current smokers with asthma before and after oral corticosteroids. METHODS:
      Exploratory study utilizing two weeks of oral dexamethasone (equivalent to 40
      mg/day prednisolone) in 22 current, 21 never and 10 ex-smokers with asthma.
      Induced sputum supernatant and plasma was obtained before and after oral
      dexamethasone. 25 cytokines were measured by multiplex microbead system
      (Invitrogen, UK) on a Luminex platform. RESULTS: Smokers with asthma had elevated
      sputum cytokine interleukin (IL) -6, -7, and -12 concentrations compared to never
      smokers with asthma. Few sputum cytokine concentrations changed in response to
      dexamethasone IL-17 and IFNalpha increased in smokers, CCL4 increased in never
      smokers and CCL5 and CXCL10 reduced in ex-smokers with asthma. Ex-smokers with
      asthma appeared to have evidence of an ongoing corticosteroid resistant elevation
      of cytokines despite smoking cessation. Several plasma cytokines were lower in
      smokers with asthma compared to never smokers with asthma. CONCLUSION: Cigarette
      smoking in asthma is associated with a corticosteroid insensitive increase in
      multiple airway cytokines. Distinct airway cytokine profiles are present in
      current smokers and never smokers with asthma and could provide an explanatory
      mechanism for the altered clinical behavior observed in smokers with asthma.

PMID- 23951171
TI  - Identification of Trypanosome proteins in plasma from African sleeping sickness
      patients infected with T. b. rhodesiense.
AB  - Control of human African sleeping sickness, caused by subspecies of the protozoan
      parasite Trypanosoma brucei, is based on preventing transmission by elimination
      of the tsetse vector and by active diagnostic screening and treatment of infected
      patients. To identify trypanosome proteins that have potential as biomarkers for
      detection and monitoring of African sleeping sickness, we have used a 'deep
      mining" proteomics approach to identify trypanosome proteins in human plasma.
      Abundant human plasma proteins were removed by immunodepletion. Depleted plasma
      samples were then digested to peptides with trypsin, fractionated by basic
      reversed phase and each fraction analyzed by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). This sample processing and analysis method enabled
      identification of low levels of trypanosome proteins in pooled plasma from late
      stage sleeping sickness patients infected with Trypanosoma brucei rhodesiense. A
      total of 254 trypanosome proteins were confidently identified. Many of the
      parasite proteins identified were of unknown function, although metabolic
      enzymes, chaperones, proteases and ubiquitin-related/acting proteins were found.
      This approach to the identification of conserved, soluble trypanosome proteins in
      human plasma offers a possible route to improved disease diagnosis and
      monitoring, since these molecules are potential biomarkers for the development of
      a new generation of antigen-detection assays. The combined immuno-depletion/mass
      spectrometric approach can be applied to a variety of infectious diseases for
      unbiased biomarker identification. 

PMID- 23951172
TI  - In vivo monitoring of angiogenesis inhibition via down-regulation of mir-21 in a
      VEGFR2-luc murine breast cancer model using bioluminescent imaging.
AB  - MicroRNA-21 (miR-21) is overexpressed in a wide range of cancers and involved in
      tumor proliferation and metastasis. However, the potential function of miR-21 in
      regulating tumor angiogenesis has been little disclosed. In this study, we
      treated the cultured 4T1 murine breast cancer cells and human umbilical vein
      endothelial cells (HUVECs) with miR-21 mimic, antagomir-21 or negative control
      (scramble), which were subjected to MTT, terminal deoxynucleotidyl transferase
      dUTP nick end labeling (TUNEL), quantitative Reverse Transcriptase PCR (qRT-PCR)
      and immunoblotting analysis. In addition, 4T1 cells were implanted beneath the
      right breast fat pad of the VEGFR2-luc transgenic mice, which were randomly
      divided into three groups and received saline, antagomir-21 or scramble treatment
      once respectively after tumor model establishment. Bioluminescent imaging was
      used to monitor tumor growth and angiogenesis in vivo at 0d, 3d, 5d, 7d, 10d, and
      14d after treatment. Mice were killed at the end of study and tumor tissues were
      collected for use. The results showed that knockdown of miR-21 by antagomir-21
      decreased cell proliferation and induced apoptosis via targeting PTEN both in 4T1
      cells and HUVECs. We also found the anti-angiogenesis and anti-tumor effects of
      antagomir-21 in the VEGFR2-luc transgenic mouse model using bioluminescent
      imaging. Moreover, the Western blotting data revealed that antagomir-21 inhibited
      tumor angiogenesis through suppressing HIF-1alpha/VEGF/VEGFR2-associated
      signaling pathway. In conclusion, the results from current study demonstrate that
      antagomir-21 can effectively suppress tumor growth and angiogenesis in VEGFR2-luc
      mouse breast tumor model and bioluminescent imaging can be used as a tool for
      noninvasively and continuously monitoring tumor angiogenesis in vivo. 

PMID- 23951174
TI  - quantitative assessment of the influence of cytochrome P450 1A2 gene polymorphism
      and colorectal cancer risk.
AB  - Cytochrome P450 1A2 (CYP1A2) encodes a member of the cytochrome P450 superfamily
      of enzymes, which play a central role in activating and detoxifying many
      carcinogens and endogenous compounds thought to be involved in the development of
      colorectal cancer (CRC). The CYP1A2*C (rs2069514) and CYP1A2*F (rs762551)
      polymorphism are two of the most commonly studied polymorphisms of the gene for
      their association with risk of CRC, but the results are conflicting. To derive a
      more precise estimation of the relationship between CYP1A2 and genetic risk of
      CRC, we performed a comprehensive meta-analysis which included 7088 cases and
      7568 controls from 12 published case-control studies. In a combined analysis, the
      summary per-allele odds ratio for CRC was 0.91 (95% CI: 0.83-1.00, P = 0.04), and
      0.91 (95% CI: 0.68-1.22, P = 0.53), for CYP1A2 *F and *C allele, respectively. In
      the subgroup analysis by ethnicity, significant associations were found in Asians
      for CYP1A2*F and CYP1A2*C, while no significant associations were detected among
      Caucasian populations. Similar results were also observed using dominant genetic
      model. Potential sources of heterogeneity were explored by subgroup analysis and
      meta-regression. No significant heterogeneity was detected in most of
      comparisons. This meta-analysis suggests that the CYP1A2 *F and *C polymorphism
      is a protective factor against CRC among Asians. 

PMID- 23951173
TI  - Amyloid-beta induced CA1 pyramidal cell loss in young adult rats is alleviated by
      systemic treatment with FGL, a neural cell adhesion molecule-derived mimetic
      peptide.
AB  - Increased levels of neurotoxic amyloid-beta in the brain are a prominent feature
      of Alzheimer's disease. FG-Loop (FGL), a neural cell adhesion molecule-derived
      peptide that corresponds to its second fibronectin type III module, has been
      shown to provide neuroprotection against a range of cellular insults. In the
      present study impairments in social recognition memory were seen 24 days after a
      5 mg/15 ul amyloid-beta(25-35) injection into the right lateral ventricle of the
      young adult rat brain. This impairment was prevented if the animal was given a
      systemic treatment of FGL. Unbiased stereology was used to investigate the
      ability of FGL to alleviate the deleterious effects on CA1 pyramidal cells of the
      amyloid-beta(25-35) injection. NeuN, a neuronal marker (for nuclear staining) was
      used to identify pyramidal cells, and immunocytochemistry was also used to
      identify inactive glycogen synthase kinase 3beta (GSK3beta) and to determine the
      effects of amyloid-beta(25-35) and FGL on the activation state of GSK3beta, since
      active GSK3beta has been shown to cause a range of AD pathologies. The cognitive
      deficits were not due to hippocampal atrophy as volume estimations of the entire
      hippocampus and its regions showed no significant loss, but amyloid-beta caused a
      40% loss of pyramidal cells in the dorsal CA1 which was alleviated partially by
      FGL. However, FGL treatment without amyloid-beta was also found to cause a 40%
      decrease in CA1 pyramidal cells. The action of FGL may be due to inactivation of
      GSK3beta, as an increased proportion of CA1 pyramidal neurons contained inactive
      GSK3beta after FGL treatment. These data suggest that FGL, although potentially
      disruptive in non-pathological conditions, can be neuroprotective in disease-like
      conditions. 

PMID- 23951175
TI  - Cognitive problem solving patterns of medical students correlate with success in
      diagnostic case solutions.
AB  - CONTEXT: Problem-solving in terms of clinical reasoning is regarded as a key
      competence of medical doctors. Little is known about the general cognitive
      actions underlying the strategies of problem-solving among medical students. In
      this study, a theory-based model was used and adapted in order to investigate the
      cognitive actions in which medical students are engaged when dealing with a case
      and how patterns of these actions are related to the correct solution. METHODS:
      Twenty-three medical students worked on three cases on clinical nephrology using
      the think-aloud method. The transcribed recordings were coded using a theory
      based model consisting of eight different cognitive actions. The coded data was
      analysed using time sequences in a graphical representation software. Furthermore
      the relationship between the coded data and accuracy of diagnosis was
      investigated with inferential statistical methods. RESULTS: The observation of
      all main actions in a case elaboration, including evaluation, representation and
      integration, was considered a complete model and was found in the majority of
      cases (56%). This pattern significantly related to the accuracy of the case
      solution (phi = 0.55; p<.001). Extent of prior knowledge was neither related to
      the complete model nor to the correct solution. CONCLUSIONS: The proposed model
      is suitable to empirically verify the cognitive actions of problem-solving of
      medical students. The cognitive actions evaluation, representation and
      integration are crucial for the complete model and therefore for the accuracy of
      the solution. The educational implication which may be drawn from this study is
      to foster students reasoning by focusing on higher level reasoning.

PMID- 23951177
TI  - Epidemiology of brucellosis and q Fever in linked human and animal populations in
      northern togo.
AB  - BACKGROUND: Although brucellosis (Brucella spp.) and Q Fever (Coxiella burnetii)
      are zoonoses of global importance, very little high quality data are available
      from West Africa. METHODS/PRINCIPAL FINDINGS: A serosurvey was conducted in
      Togo's main livestock-raising zone in 2011 in 25 randomly selected villages,
      including 683 people, 596 cattle, 465 sheep and 221 goats. Additionally, 464
      transhumant cattle from Burkina Faso were sampled in 2012. The serological
      analyses performed were the Rose Bengal Test and ELISA for brucellosis and ELISA
      and the immunofluorescence assay (IFA) for Q Fever Brucellosis did not appear to
      pose a major human health problem in the study zone, with only 7 seropositive
      participants. B. abortus was isolated from 3 bovine hygroma samples, and is
      likely to be the predominant circulating strain. This may explain the observed
      seropositivity amongst village cattle (9.2%, 95%CI:4.3-18.6%) and transhumant
      cattle (7.3%, 95%CI:3.5-14.7%), with an absence of seropositive small ruminants.
      Exposure of livestock and people to C. burnetii was common, potentially
      influenced by cultural factors. People of Fulani ethnicity had greater livestock
      contact and a significantly higher seroprevalence than other ethnic groups
      (Fulani: 45.5%, 95%CI:37.7-53.6%; non-Fulani: 27.1%, 95%CI:20.6-34.7%).
      Appropriate diagnostic test cut-off values in endemic settings requires further
      investigation. Both brucellosis and Q Fever appeared to impact on livestock
      production. Seropositive cows were more likely to have aborted a foetus during
      the previous year than seronegative cows, when adjusted for age. This odds was
      3.8 times higher (95%CI: 1.2-12.1) for brucellosis and 6.7 times higher (95%CI:
      1.3-34.8) for Q Fever. CONCLUSIONS: This is the first epidemiological study of
      zoonoses in Togo in linked human and animal populations, providing much needed
      data for West Africa. Exposure to Brucella and C. burnetii is common but further
      research is needed into the clinical and economic impact.

PMID- 23951178
TI  - Clinical factors for severity of Plasmodium falciparum malaria in hospitalized
      adults in Thailand.
AB  - Plasmodium falciparum is a major cause of severe malaria in Southeast Asia,
      however, there is limited information regarding clinical factors associated with
      the severity of falciparum malaria from this region. We performed a retrospective
      case-control study to compare clinical factors and outcomes between patients with
      severe and non-severe malaria, and to identify clinical factors associated with
      the requirement for intensive care unit (ICU) admission of patients with severe
      falciparum malaria among hospitalized adults in Southeast Asia. A total of 255
      patients with falciparum malaria in the Hospital for Tropical Diseases in
      Bangkok, Thailand between 2006 and 2012 were included. We identified 104 patients
      with severe malaria (cases) and 151 patients with non-severe malaria (controls).
      Patients with falciparum malaria with following clinical and laboratory
      characteristics on admission (1) referrals, (2) no prior history of malaria, (3)
      body temperature of >38.5 degrees C, (4) white blood cell counts >10*10(9)/uL,
      (5) presence of schizonts in peripheral blood smears, and (6) albumin
      concentrations of <3.5 g/dL, were more likely to develop severe malaria (P<0.05).
      Among patients with severe malaria, patients who met >=3 of the 2010 WHO criteria
      had sensitivity of 79.2% and specificity of 81.8% for requiring ICU admission.
      Multivariate analysis identified the following as independent associated factors
      for severe malaria requiring ICU admission; (1) ethnicity of Thai [odds ratio
      (OR) = 3.601, 95% confidence interval (CI) = 1.011-12.822] or Myanmar [OR =
      3.610, 95% CI = 1.138-11.445]; (2) referrals [OR = 3.571, 95% CI = 1.306-9.762];
      (3) no prior history of malaria [OR = 5.887, 95% CI = 1.354-25.594]; and (4)
      albumin concentrations of <3.5 g/dL [OR = 7.200, 95% CI = 1.802-28.759]. Our
      findings are important for the clinical management of patients with malaria
      because it can help early identification of patients that could develop severe
      malaria and require ICU admission. Early identification and the timely initiation
      of appropriate treatments may well improve the outcomes and reduce the mortality
      of these patients. 

PMID- 23951176
TI  - The major brain endocannabinoid 2-AG controls neuropathic pain and mechanical
      hyperalgesia in patients with neuromyelitis optica.
AB  - Recurrent myelitis is one of the predominant characteristics in patients with
      neuromyelitis optica (NMO). While paresis, visual loss, sensory deficits, and
      bladder dysfunction are well known symptoms in NMO patients, pain has been
      recognized only recently as another key symptom of the disease. Although spinal
      cord inflammation is a defining aspect of neuromyelitis, there is an almost
      complete lack of data on altered somatosensory function, including pain.
      Therefore, eleven consecutive patients with NMO were investigated regarding the
      presence and clinical characteristics of pain. All patients were examined
      clinically as well as by Quantitative Sensory Testing (QST) following the
      protocol of the German Research Network on Neuropathic Pain (DFNS). Additionally,
      plasma endocannabinoid levels and signs of chronic stress and depression were
      determined. Almost all patients (10/11) suffered from NMO-associated neuropathic
      pain for the last three months, and 8 out of 11 patients indicated relevant pain
      at the time of examination. Symptoms of neuropathic pain were reported in the
      vast majority of patients with NMO. Psychological testing revealed signs of
      marked depression. Compared to age and gender-matched healthy controls, QST
      revealed pronounced mechanical and thermal sensory loss, strongly correlated to
      ongoing pain suggesting the presence of deafferentation-induced neuropathic pain.
      Thermal hyperalgesia correlated to MRI-verified signs of spinal cord lesion. Heat
      hyperalgesia was highly correlated to the time since last relapse of NMO.
      Patients with NMO exhibited significant mechanical and thermal dysesthesia,
      namely dynamic mechanical allodynia and paradoxical heat sensation. Moreover,
      they presented frequently with either abnormal mechanical hypoalgesia or
      hyperalgesia, which depended significantly on plasma levels of the endogenous
      cannabinoid 2-arachidonoylglycerole (2-AG). These data emphasize the high
      prevalence of neuropathic pain and hyperalgesia in patients with NMO. The degree
      of mechanical hyperalgesia reflecting central sensitization of nociceptive
      pathways seems to be controlled by the major brain endocannabinoid 2-AG. 

PMID- 23951179
TI  - Trichostatin A modulates thiazolidinedione-mediated suppression of tumor necrosis
      factor alpha-induced lipolysis in 3T3-L1 adipocytes.
AB  - In obesity, high levels of tumor necrosis factor alpha (TNFalpha) stimulate
      lipolysis in adipocytes, leading to hyperlipidemia and insulin resistance.
      Thiazolidinediones (TZDs), the insulin-sensitizing drugs, antagonize TNFalpha
      induced lipolysis in adipocytes, thereby increasing insulin sensitivity in
      diabetes patients. The cellular target of TZDs is peroxisome proliferator
      activated receptor gamma (PPARgamma), a nuclear receptor that controls many
      adipocyte functions. As a transcription factor, PPARgamma is closely modulated by
      coregulators, which include coactivators and corepressors. Previous studies have
      revealed that in macrophages, the insulin-sensitizing effect of PPARgamma may
      involve suppression of proinflammatory gene expression by recruiting the
      corepressor complex that contains corepressors and histone deacetylases (HDACs).
      Therefore, we investigated whether the corepressor complex is involved in TZD
      mediated suppression of TNFalpha-induced lipolysis in 3T3-L1 adipocytes.
      Trichostatin A (TSA), a pan HDAC inhibitor (HDACI) that inhibits class I and II
      HDACs, was used to examine the involvement of HDACs in the actions of TZDs. TSA
      alone increased basal lipolysis and attenuated TZD-mediated suppression of
      TNFalpha-induced lipolysis. Increased basal lipolysis may in part result from
      class I HDAC inhibition because selective class I HDACI treatment had similar
      results. However, attenuation of TZD-mediated TNFalpha antagonism may be specific
      to TSA and related hydroxamate-based HDACI rather than to HDAC inhibition.
      Consistently, corepressor depletion did not affect TZD-mediated suppression.
      Interestingly, TSA treatment greatly reduced PPARgamma levels in differentiated
      adipocytes. Finally, extracellular signal-related kinase 1/2 (ERK1/2) mediated
      TNFalpha-induced lipolysis, and TZDs suppressed TNFalpha-induced ERK
      phosphorylation. We determined that TSA increased basal ERK phosphorylation, and
      attenuated TZD-mediated suppression of TNFalpha-induced ERK phosphorylation,
      consistent with TSA's effects on lipolysis. These studies suggest that TSA,
      through down-regulating PPARgamma, attenuates TZD-mediated suppression of
      TNFalpha-induced ERK phosphorylation and lipolysis in adipocytes. 

PMID- 23951180
TI  - Mapping C-terminal transactivation domains of the nuclear HER family receptor
      tyrosine kinase HER3.
AB  - Nuclear localized HER family receptor tyrosine kinases (RTKs) have been observed
      in primary tumor specimens and cancer cell lines for nearly two decades. Inside
      the nucleus, HER family members (EGFR, HER2, and HER3) have been shown to
      function as co-transcriptional activators for various cancer-promoting genes.
      However, the regions of each receptor that confer transcriptional potential
      remain poorly defined. The current study aimed to map the putative
      transactivation domains (TADs) of the HER3 receptor. To accomplish this goal,
      various intracellular regions of HER3 were fused to the DNA binding domain of the
      yeast transcription factor Gal4 (Gal4DBD) and tested for their ability to
      transactivate Gal4 UAS-luciferase. Results from these analyses demonstrated that
      the C-terminal domain of HER3 (CTD, amino acids distal to the tyrosine kinase
      domain) contained potent transactivation potential. Next, nine HER3-CTD
      truncation mutants were constructed to map minimal regions of transactivation
      potential using the Gal4 UAS-luciferase based system. These analyses identified a
      bipartite region of 34 (B1) and 27 (B2) amino acids in length that conferred the
      majority of HER3's transactivation potential. Next, we identified full-length
      nuclear HER3 association and regulation of a 122 bp region of the cyclin D1
      promoter. To understand how the B1 and B2 regions influenced the transcriptional
      functions of nuclear HER3, we performed cyclin D1 promoter-luciferase assays in
      which HER3 deleted of the B1 and B2 regions was severely hindered in regulating
      this promoter. Further, the overexpression of HER3 enhanced cyclin D1 mRNA
      expression, while HER3 deleted of its identified TADs was hindered at doing so.
      Thus, the ability for HER3 to function as a transcriptional co-activator may be
      dependent on specific C-terminal TADs.

PMID- 23951181
TI  - An Outbreak of Human Fascioliasis gigantica in Southwest China.
AB  - Fascioliasis is a common parasitic disease in livestock in China. However, human
      fascioliasis is rarely reported in the country. Here we describe an outbreak of
      human fascioliasis in Yunnan province. We reviewed the complete clinical records
      of 29 patients and performed an epidemiological investigation on the general
      human population and animals in the outbreak locality. Our findings support an
      outbreak due to Fasciola gigantica with a peak in late November, 2011. The most
      common symptoms were remittent fever, epigastric tenderness, and hepatalgia.
      Eosinophilia and tunnel-like lesions in ultrasound imaging in the liver were also
      commonly seen. Significant improvement of patients' condition was achieved by
      administration of triclabendazole(r). Fasciola spp. were discovered in local
      cattle (28.6%) and goats (26.0%). Molecular evidence showed a coexistence of F.
      gigantica and F. hepatica. However, all eggs seen in humans were confirmed to be
      F. gigantica. Herb (Houttuynia cordata) was most likely the source of infections.
      Our findings indicate that human fascioliasis is a neglected disease in China.
      The distribution of triclabendazole(r), the only efficacious drug against human
      fascioliasis, should be promoted. 

PMID- 23951182
TI  - Distribution, sources and risk assessment of polychlorinated biphenyls in soils
      from the Midway Atoll, North Pacific Ocean.
AB  - Concentrations of 28 polychlorinated biphenyls (PCBs) were assessed in soils from
      the Midway Atoll in the central North Pacific Ocean. The analytical procedure
      involved the application of accelerated solvent extraction (ASE) and gas
      chromatography coupled with ion trap mass spectrometric detection (GC/ITMS) for
      identification and quantification. Among the 28 PCB congeners studied, 26 of
      them, except CB195 and CB209, were detected in the analyzed samples at different
      frequencies. The total concentrations of 28 indicator PCBs (SigmaPCBs) ranged
      from 2.6 to 148.8 ng g-1 with an average value of 50.7 ng g-1 and median of 39.5
      ng g-1. Sources and congeners' pattern of PCB were investigated in the soil of
      Midway Atoll. The principal component analysis indicated that the compositions of
      PCBs in most of the soil samples were similar. The total concentrations of PCBs
      were used to assess the cancer risk probabilities in humans via ingestion, dermal
      contact and inhalation of soil particles. Very low cancer risk was found in all
      soil samples caused by SigmaPCBs.

PMID- 23951183
TI  - Use of a dual reporter plasmid to demonstrate Bactofection with an attenuated
      AroA(-) derivative of Pasteurella multocida B:2.
AB  - A reporter plasmid pSRG has been developed which expresses red fluorescent
      protein (RFP) from a constitutive prokaryotic promoter within Pasteurella
      multocida B:2 and green fluorescent protein (GFP) from a constitutive eukaryotic
      promoter within mammalian cells. This construct has been used to determine the
      location and viability of the bacteria when moving from the extracellular
      environment into the intracellular compartment of mammalian cells. Invasion
      assays with embryonic bovine lung (EBL) cells and an attenuated AroA(-)
      derivative of Pasteurella multocida B:2 (strain JRMT12), harbouring the plasmid
      pSRG, showed that RFP-expressing bacteria could be detected intracellularly at 3
      h post-invasion. At this stage, some EBL cells harbouring RFP-expressing bacteria
      were observed to express GFP simultaneously, indicating release of the plasmid
      into the intracellular environment. At 5 h post-invasion, more EBL cells were
      expressing GFP, while still harbouring RFP-expressing bacteria. Concurrently,
      some EBL cells were shown to express only GFP, indicating loss of viable bacteria
      within these cells. These experiments proved the functionality of the pSRG dual
      reporter system and the potential of P. multocida B:2 JRMT12 for bactofection and
      delivery of a DNA vaccine. 

PMID- 23951184
TI  - A viral-human interactome based on structural motif-domain interactions captures
      the human infectome.
AB  - Protein interactions between a pathogen and its host are fundamental in the
      establishment of the pathogen and underline the infection mechanism. In the
      present work, we developed a single predictive model for building a host-viral
      interactome based on the identification of structural descriptors from motif
      domain interactions of protein complexes deposited in the Protein Data Bank
      (PDB). The structural descriptors were used for searching, in a database of
      protein sequences of human and five clinically important viruses; therefore,
      viral and human proteins sharing a descriptor were predicted as interacting
      proteins. The analysis of the host-viral interactome allowed to identify a set of
      new interactions that further explain molecular mechanism associated with viral
      infections and showed that it was able to capture human proteins already
      associated to viral infections (human infectome) and non-infectious diseases
      (human diseasome). The analysis of human proteins targeted by viral proteins in
      the context of a human interactome showed that their neighbors are enriched in
      proteins reported with differential expression under infection and disease
      conditions. It is expected that the findings of this work will contribute to the
      development of systems biology for infectious diseases, and help guide the
      rational identification and prioritization of novel drug targets. 

PMID- 23951185
TI  - The multifunctional Ca2+/calmodulin-dependent kinase IIdelta (CaMKIIdelta)
      regulates arteriogenesis in a mouse model of flow-mediated remodeling.
AB  - OBJECTIVE: Sustained hemodynamic stress mediated by high blood flow promotes
      arteriogenesis, the outward remodeling of existing arteries. Here, we examined
      whether Ca2+/calmodulin-dependent kinase II (CaMKII) regulates arteriogenesis.
      METHODS AND RESULTS: Ligation of the left common carotid led to an increase in
      vessel diameter and perimeter of internal and external elastic lamina in the
      contralateral, right common carotid. Deletion of CaMKIIdelta (CaMKIIdelta-/-)
      abolished this outward remodeling. Carotid ligation increased CaMKII expression
      and was associated with oxidative activation of CaMKII in the adventitia and
      endothelium. Remodeling was abrogated in a knock-in model in which oxidative
      activation of CaMKII is abolished. Early after ligation, matrix metalloproteinase
      9 (MMP9) was robustly expressed in the adventitia of right carotid arteries of WT
      but not CaMKIIdelta-/- mice. MMP9 mainly colocalized with adventitial
      macrophages. In contrast, we did not observe an effect of CaMKIIdelta deficiency
      on other proposed mediators of arteriogenesis such as expression of adhesion
      molecules or smooth muscle proliferation. Transplantation of WT bone marrow into
      CaMKIIdelta-/- mice normalized flow-mediated remodeling. CONCLUSION: CaMKIIdelta
      is activated by oxidation under high blood flow conditions and is required for
      flow-mediated remodeling through a mechanism that includes increased MMP9
      expression in bone marrow-derived cells invading the arterial wall.

PMID- 23951186
TI  - Long term effects of aversive reinforcement on colour discrimination learning in
      free-flying bumblebees.
AB  - The results of behavioural experiments provide important information about the
      structure and information-processing abilities of the visual system.
      Nevertheless, if we want to infer from behavioural data how the visual system
      operates, it is important to know how different learning protocols affect
      performance and to devise protocols that minimise noise in the response of
      experimental subjects. The purpose of this work was to investigate how
      reinforcement schedule and individual variability affect the learning process in
      a colour discrimination task. Free-flying bumblebees were trained to discriminate
      between two perceptually similar colours. The target colour was associated with
      sucrose solution, and the distractor could be associated with water or quinine
      solution throughout the experiment, or with one substance during the first half
      of the experiment and the other during the second half. Both acquisition and
      final performance of the discrimination task (measured as proportion of correct
      choices) were determined by the choice of reinforcer during the first half of the
      experiment: regardless of whether bees were trained with water or quinine during
      the second half of the experiment, bees trained with quinine during the first
      half learned the task faster and performed better during the whole experiment.
      Our results confirm that the choice of stimuli used during training affects the
      rate at which colour discrimination tasks are acquired and show that early
      contact with a strongly aversive stimulus can be sufficient to maintain high
      levels of attention during several hours. On the other hand, bees which took more
      time to decide on which flower to alight were more likely to make correct choices
      than bees which made fast decisions. This result supports the existence of a
      trade-off between foraging speed and accuracy, and highlights the importance of
      measuring choice latencies during behavioural experiments focusing on cognitive
      abilities. 

PMID- 23951187
TI  - Oxaliplatin and its enantiomer induce different condensation dynamics of single
      DNA molecules.
AB  - The interactions of DNA with oxaliplatin (Pt(R,R-DACH)) or its enantiomer (Pt(S,S
      DACH)) were investigated using magnetic tweezers and atomic force microscope. In
      the process of DNA condensation induced by Pt-DACH, only diadducts and micro
      loops are formed at low Pt-DACH concentrations, while at high Pt-DACH
      concentrations, besides the diadducts and micro-loops, long-range cross-links are
      also formed. The diadduct formation rate of Pt(R,R-DACH) is higher than that of
      Pt(S,S-DACH). However, the proportions of micro-loops and long-range cross-links
      for Pt(S,S-DACH) are higher than those for Pt(R,R-DACH). We propose a model to
      explain these differences between the effect of Pt(R,R-DACH) and that of Pt(S,S
      DACH) on DNA condensation. The study has strong implications for the
      understanding of the effect of chirality on the interaction between Pt-DACH and
      DNA and the kinetics of DNA condensation induced by platinum complexes. 

PMID- 23951188
TI  - Forest structure, stand composition, and climate-growth response in montane
      forests of Jiuzhaigou National Nature Reserve, China.
AB  - Montane forests of western China provide an opportunity to establish baseline
      studies for climate change. The region is being impacted by climate change, air
      pollution, and significant human impacts from tourism. We analyzed forest stand
      structure and climate-growth relationships from Jiuzhaigou National Nature
      Reserve in northwestern Sichuan province, along the eastern edge of the Tibetan
      plateau. We conducted a survey to characterize forest stand diversity and
      structure in plots occurring between 2050 and 3350 m in elevation. We also
      evaluated seedling and sapling recruitment and tree-ring data from four conifer
      species to assess: 1) whether the forest appears in transition toward increased
      hardwood composition; 2) if conifers appear stressed by recent climate change
      relative to hardwoods; and 3) how growth of four dominant species responds to
      recent climate. Our study is complicated by clear evidence of 20(th) century
      timber extraction. Focusing on regions lacking evidence of logging, we found a
      diverse suite of conifers (Pinus, Abies, Juniperus, Picea, and Larix) strongly
      dominate the forest overstory. We found population size structures for most
      conifer tree species to be consistent with self-replacement and not providing
      evidence of shifting composition toward hardwoods. Climate-growth analyses
      indicate increased growth with cool temperatures in summer and fall. Warmer
      temperatures during the growing season could negatively impact conifer growth,
      indicating possible seasonal climate water deficit as a constraint on growth. In
      contrast, however, we found little relationship to seasonal precipitation.
      Projected warming does not yet have a discernible signal on trends in tree growth
      rates, but slower growth with warmer growing season climates suggests reduced
      potential future forest growth. 

PMID- 23951189
TI  - Transcriptome characteristics and six alternative expressed genes positively
      correlated with the phase transition of annual cambial activities in Chinese Fir
      (Cunninghamia lanceolata (Lamb.) Hook).
AB  - BACKGROUND: The molecular mechanisms that govern cambial activity in angiosperms
      are well established, but little is known about these molecular mechanisms in
      gymnosperms. Chinese fir (Cunninghamia lanceolata (Lamb.) Hook), a diploid (2n  =
      2x  = 22) gymnosperm, is one of the most important industrial and commercial
      timber species in China. Here, we performed transcriptome sequencing to identify
      the repertoire of genes expressed in cambium tissue of Chinese fir.
      METHODOLOGY/PRINCIPAL FINDINGS: Based on previous studies, the four stage
      specific cambial tissues of Chinese fir were defined using transmission electron
      microscopy (TEM). In total, 20 million sequencing reads (3.6 Gb) were obtained
      using Illumina sequencing from Chinese fir cambium tissue collected at active
      growth stage, with a mean length of 131 bp and a N50 of 90 bp. SOAPdenovo
      software was used to assemble 62,895 unigenes. These unigenes were further
      functionally annotated by comparing their sequences to public protein databases.
      Expression analysis revealed that the altered expression of six homologous genes
      (ClWOX1, ClWOX4, ClCLV1-like, ClCLV-like, ClCLE12, and ClPIN1-like) correlated
      positively with changes in cambial activities; moreover, these six genes might be
      directly involved in cambial function in Chinese fir. Further, the full-length
      cDNAs and DNAs for ClWOX1 and ClWOX4 were cloned and analyzed. CONCLUSIONS: In
      this study, a large number of tissue/stage-specific unigene sequences were
      generated from the active growth stage of Chinese fir cambium. Transcriptome
      sequencing of Chinese fir not only provides extensive genetic resources for
      understanding the molecular mechanisms underlying cambial activities in Chinese
      fir, but also is expected to be an important foundation for future genetic
      studies of Chinese fir. This study indicates that ClWOX1 and ClWOX4 could be
      possible reverse genetic target genes for revealing the molecular mechanisms of
      cambial activities in Chinese fir.

PMID- 23951192
TI  - Influence of turn-taking in a two-person conversation on the gaze of a viewer.
AB  - In natural conversation, the minimal gaps and overlaps of the turns at talk
      indicate an accurate regulation of the timings of the turn-taking system. Here we
      studied how the turn-taking affects the gaze of a non-involved viewer of a two
      person conversation. The subjects were presented with a video of a conversation
      while their eye gaze was tracked with an infrared camera. As a control, the video
      was presented without sound and the sound with still image of the speakers. Turns
      at talk directed the gaze behaviour of the viewers; the gaze followed, rather
      than predicted, the speakership change around the turn transition. Both visual
      and auditory cues presented alone also induced gaze shifts towards the speaking
      person, although significantly less and later than when the cues of both
      modalities were available. These results show that the organization of turn
      taking has a strong influence on the gaze patterns of even non-involved viewers
      of the conversation, and that visual and auditory cues are in part redundant in
      guiding the viewers' gaze. 

PMID- 23951191
TI  - Anti-arrhythmic effect of verapamil is accompanied by preservation of cx43
      protein in rat heart.
AB  - The present study was to test the hypothesis that anti-arrhythmic properties of
      verapamil may be accompanied by preserving connexin43 (Cx43) protein via calcium
      influx inhibition. In an in vivo study, myocardial ischemic arrhythmia was
      induced by occlusion of the left anterior descending (LAD) coronary artery for 45
      min in Sprague-Dawley rats. Verapamil, a calcium channel antagonist, was injected
      i.v. into a femoral vein prior to ischemia. Effects of verapamil on arrhythmias
      induced by Bay K8644 (a calcium channel agonist) were also determined. In an ex
      vivo study, the isolated heart underwent an initial 10 min of baseline normal
      perfusion and was subjected to high calcium perfusion in the absence or presence
      of verapamil. Cardiac arrhythmia was measured by electrocardiogram (ECG) and Cx43
      protein was determined by immunohistochemistry and western blotting.
      Administration of verapamil prior to myocardial ischemia significantly reduced
      the incidence of ventricular arrhythmias and total arrhythmia scores, with the
      reductions in heat rate, mean arterial pressure and left ventricular systolic
      pressure. Verapamil also inhibited arrhythmias induced by Bay K8644 and high
      calcium perfusion. Effect of verapamil on ischemic arrhythmia scores was
      abolished by heptanol, a Cx43 protein uncoupler and Gap 26, a Cx43 channels
      inhibitor. Immunohistochemistry data showed that ischemia-induced redistribution
      and reduced immunostaining of Cx43 were prevented by verapamil. In addition,
      diminished expression of Cx43 protein determined by western blotting was observed
      following myocardial ischemia in vivo or following high calcium perfusion ex vivo
      and was preserved after verapamil administration. Our data suggest that verapamil
      may confer an anti-arrhythmic effect via calcium influx inhibition, inhibition of
      oxygen consumption and accompanied by preservation of Cx43 protein. 

PMID- 23951190
TI  - Improvement of PHBV scaffolds with bioglass for cartilage tissue engineering.
AB  - Polymer scaffold systems consisting of poly(hydroxybutyrate-co-hydroxyvalerate)
      (PHBV) have proven to be possible matrices for the three-dimensional growth of
      chondrocyte cultures. However, the engineered cartilage grown on these PHBV
      scaffolds is currently unsatisfactory for clinical applications due to PHBV's
      poor hydrophilicity, resulting in inadequate thickness and poor biomechanical
      properties of the engineered cartilage. It has been reported that the
      incorporation of Bioglass (BG) into PHBV can improve the hydrophilicity of the
      composites. In this study, we compared the effects of PHBV scaffolds and PHBV/BG
      composite scaffolds on the properties of engineered cartilage in vivo. Rabbit
      articular chondrocytes were seeded into PHBV scaffolds and PHBV/BG scaffolds.
      Short-term in vitro culture followed by long-term in vivo transplantation was
      performed to evaluate the difference in cartilage regeneration between the
      cartilage layers grown on PHBV and PHBV/BG scaffolds. The results show that the
      incorporation of BG into PHBV efficiently improved both the hydrophilicity of the
      composites and the percentage of adhered cells and promoted cell migration into
      the inner part the constructs. With prolonged incubation time in vivo, the
      chondrocyte-scaffold constructs in the PHBV/BG group formed thicker cartilage
      like tissue with better biomechanical properties and a higher cartilage matrix
      content than the constructs in the PHBV/BG group. These results indicate that
      PHBV/BG scaffolds can be used to prepare better engineered cartilage than pure
      PHBV. 

PMID- 23951193
TI  - Cyclosporine A impairs the macrophage reverse cholesterol transport in mice by
      reducing sterol fecal excretion.
AB  - Despite the efficacy in reducing acute rejection events in organ transplanted
      subjects, long term therapy with cyclosporine A is associated with increased
      atherosclerotic cardiovascular morbidity. We studied whether this drug affects
      the antiatherogenic process of the reverse cholesterol transport from macrophages
      in vivo. Cyclosporine A 50 mg/kg/d was administered to C57BL/6 mice by
      subcutaneous injection for 14 days. Macrophage reverse cholesterol transport was
      assessed by following [(3)H]-cholesterol mobilization from pre-labeled
      intraperitoneally injected macrophages, expressing or not apolipoprotein E, to
      plasma, liver and feces. The pharmacological treatment significantly reduced the
      amount of radioactive sterols in the feces, independently on the expression of
      apolipoprotein E in the macrophages injected into recipient mice and in absence
      of changes of plasma levels of high density lipoprotein-cholesterol. Gene
      expression analysis revealed that cyclosporine A inhibited the hepatic levels of
      cholesterol 7-alpha-hydroxylase, concomitantly with the increase in hepatic and
      intestinal expression of ATP Binding Cassette G5. However, the in vivo relevance
      of the last observation was challenged by the demonstration that mice treated or
      not with cyclosporine A showed the same levels of circulating beta-sitosterol.
      These results indicate that treatment of mice with cyclosporine A impaired the
      macrophage reverse cholesterol transport by reducing fecal sterol excretion,
      possibly through the inhibition of cholesterol 7-alpha-hydroxylase expression.
      The current observation may provide a potential mechanism for the high incidence
      of atherosclerotic coronary artery disease following the immunosuppressant
      therapy in organ transplanted recipients. 

PMID- 23951194
TI  - Mapping, bayesian geostatistical analysis and spatial prediction of lymphatic
      filariasis prevalence in Africa.
AB  - There is increasing interest to control or eradicate the major neglected tropical
      diseases. Accurate modelling of the geographic distributions of parasitic
      infections will be crucial to this endeavour. We used 664 community level
      infection prevalence data collated from the published literature in conjunction
      with eight environmental variables, altitude and population density, and a
      multivariate Bayesian generalized linear spatial model that allows explicit
      accounting for spatial autocorrelation and incorporation of uncertainty in input
      data and model parameters, to construct the first spatially-explicit map
      describing LF prevalence distribution in Africa. We also ran the best-fit model
      against predictions made by the HADCM3 and CCCMA climate models for 2050 to
      predict the likely distributions of LF under future climate and population
      changes. We show that LF prevalence is strongly influenced by spatial
      autocorrelation between locations but is only weakly associated with
      environmental covariates. Infection prevalence, however, is found to be related
      to variations in population density. All associations with key
      environmental/demographic variables appear to be complex and non-linear. LF
      prevalence is predicted to be highly heterogenous across Africa, with high
      prevalences (>20%) estimated to occur primarily along coastal West and East
      Africa, and lowest prevalences predicted for the central part of the continent.
      Error maps, however, indicate a need for further surveys to overcome problems
      with data scarcity in the latter and other regions. Analysis of future changes in
      prevalence indicates that population growth rather than climate change per se
      will represent the dominant factor in the predicted increase/decrease and spread
      of LF on the continent. We indicate that these results could play an important
      role in aiding the development of strategies that are best able to achieve the
      goals of parasite elimination locally and globally in a manner that may also
      account for the effects of future climate change on parasitic infection. 

PMID- 23951195
TI  - Behavioral inhibition in rhesus monkeys (Macaca mulatta) is related to the
      airways response, but not immune measures, commonly associated with asthma.
AB  - Behavioral inhibition reflects a disposition to react warily to novel situations,
      and has been associated with atopic diseases such as asthma. Retrospective work
      established the relationship between behavioral inhibition in rhesus monkeys
      (Macaca mulatta) and airway hyperresponsiveness, but not atopy, and the
      suggestion was made that behavioral inhibition might index components of asthma
      that are not immune-related. In the present study, we prospectively examined the
      relationship between behavioral inhibition and airway hyperresponsiveness, and
      whether hormonal and immune measures often associated with asthma were associated
      with behavioral inhibition and/or airway hyperresponsiveness. In a sample of 49
      yearling rhesus monkeys (mean=1.25 years, n=24 behaviorally inhibited animals),
      we measured in vitro cytokine levels (IL-4, IL-10, IL-12, IFN-gamma) in response
      to stimulation, as well as peripheral blood cell percentages, cortisol levels,
      and percentage of regulatory T-cells (CD3+CD4+CD25+FOXP3+). Airway reactivity was
      assessed using an inhaled methacholine challenge. Bronchoalveolar lavage was
      performed and the proportion of immune cells was determined. Behaviorally
      inhibited monkeys had airway hyperresponsiveness as indicated by the methacholine
      challenge (p=0.031), confirming our earlier retrospective result. Airway
      hyperresponsiveness was also associated with lower lymphocyte percentages in
      lavage fluid and marginally lower plasma cortisol concentrations. However, none
      of the tested measures was significantly related to both behavioral inhibition
      and airway hyperresponsiveness, and so could not mediate their relationship.
      Airway hyperresponsiveness is common to atopic and non-atopic asthma and
      behavioral inhibition has been related to altered autonomic activity in other
      studies. Our results suggest that behavioral inhibition might index an
      autonomically mediated reactive airway phenotype, and that a variety of stimuli
      (including inflammation within lung tissue that is not specifically associated
      with behavioral inhibition) may trigger the airways response.

PMID- 23951197
TI  - Youth in India ready for sex education? Emerging evidence from national surveys.
AB  - CONTEXT: Sex education/family life education (FLE) has been one of the highly
      controversial issues in Indian society. Due to increasing incidences of HIV/AIDS,
      RTIs/STIs and teenage pregnancies, there is a rising need to impart sex
      education. However, introducing sex education at school level always received
      mixed response from various segments of Indian society. DATA AND METHODS: We
      attempt to understand the expectations and experiences of youth regarding family
      life education in India by analysing the data from District Level Household and
      Facility Survey (DLHS-3: 2007-08) and Youth Study in India (2006-07). We used
      descriptive methods to analyse the extent of access to FLE and socio demographic
      patterning among Indian youth. RESULTS AND DISCUSSIONS: We found substantial gap
      between the proportion of youth who perceived sex education to be important and
      those who actually received it, revealing considerable unmet need for FLE. Youth
      who received FLE were relatively more aware about reproductive health issues than
      their counterparts. Majority among Indian youth, irrespective of their age and
      sex, favoured introduction of FLE at school level, preferably from standard 8(th)
      onwards. The challenge now is to develop a culturally-sensitive FLE curriculum
      acceptable to all sections of society.

PMID- 23951196
TI  - Sirt1 inhibits akt2-mediated porcine adipogenesis potentially by direct protein
      protein interaction.
AB  - Compared with the rodent, the domestic pig is a much better animal model for
      studying adipogenesis and obesity-related diseases. Currently, the role of Akt2
      and Sirt1 in porcine adipogenesis remains elusive. In this study, we defined the
      effect of Akt2 and Sirt1 on porcine preadipocyte lipogenesis and the regulatory
      mechanism. First, we found that Akt2 was widely expressed in porcine various
      tissues and at high level in adipose tissue. Further analysis showed that the
      expression level of Akt2 was much higher in adipose tissue and adipocytes of the
      Bamei pig breed (a Chinese indigenous fatty pig) than in that of the Large White
      pig breed (a Lean type pig), whereas the level of Sirt1 expression was opposite.
      The expression levels of Sirt1 and Akt2 gradually increased during adipogenic
      differentiation. Adipogenesis was robustly inhibited in Akt2 deficient fat cells,
      whereas it was promoted in Sirt1 deficient cells using the lentiviral-mediated
      shRNA approach. Interestingly, adipogenesis returned to normal in Akt2 and Sirt1
      dual-deficient cells, showing that the pro- and anti-adipogenic effects were
      balanced. Sirt1 inhibited transcriptional activity of Akt2 in a dose-dependent
      way. Interaction of endogenous Akt2 and Sirt1 was gradually enhanced before day 6
      of differentiation, and then attenuated. Akt2 and Sirt1 also interacted with
      C/EBPalpha in adipocytes. Moreover, knockdown of Akt2 or/and Sirt1 affected pro
      lipogenesis of insulin-stimulated by PI3K/Akt pathway. We further found that
      Sirt1 respectively interacted with PI3K and GSK3beta which were key upstream and
      downstream components of PI3K/Akt pathway. Based on the above findings, we
      concluded that the crosstalk between C/EBPalpha and PI3K/Akt signaling pathways
      is implicated in Akt2 and Sirt1 regulation of adipogenesis. 

PMID- 23951198
TI  - Fatigue shifts and scatters heart rate variability in elite endurance athletes.
AB  - PURPOSE: This longitudinal study aimed at comparing heart rate variability (HRV)
      in elite athletes identified either in 'fatigue' or in 'no-fatigue' state in
      'real life' conditions. METHODS: 57 elite Nordic-skiers were surveyed over 4
      years. R-R intervals were recorded supine (SU) and standing (ST). A fatigue state
      was quoted with a validated questionnaire. A multilevel linear regression model
      was used to analyze relationships between heart rate (HR) and HRV descriptors
      [total spectral power (TP), power in low (LF) and high frequency (HF) ranges
      expressed in ms(2) and normalized units (nu)] and the status without and with
      fatigue. The variables not distributed normally were transformed by taking their
      common logarithm (log10). RESULTS: 172 trials were identified as in a 'fatigue'
      and 891 as in 'no-fatigue' state. All supine HR and HRV parameters (Beta+/-SE)
      were significantly different (P<0.0001) between 'fatigue' and 'no-fatigue': HRSU
      (+6.27+/-0.61 bpm), logTPSU (-0.36+/-0.04), logLFSU (-0.27+/-0.04), logHFSU (
      0.46+/-0.05), logLF/HFSU (+0.19+/-0.03), HFSU(nu) (-9.55+/-1.33). Differences
      were also significant (P<0.0001) in standing: HRST (+8.83+/-0.89), logTPST (
      0.28+/-0.03), logLFST (-0.29+/-0.03), logHFST (-0.32+/-0.04). Also, intra
      individual variance of HRV parameters was larger (P<0.05) in the 'fatigue' state
      (logTPSU: 0.26 vs. 0.07, logLFSU: 0.28 vs. 0.11, logHFSU: 0.32 vs. 0.08, logTPST:
      0.13 vs. 0.07, logLFST: 0.16 vs. 0.07, logHFST: 0.25 vs. 0.14). CONCLUSION: HRV
      was significantly lower in 'fatigue' vs. 'no-fatigue' but accompanied with larger
      intra-individual variance of HRV parameters in 'fatigue'. The broader intra
      individual variance of HRV parameters might encompass different changes from no
      fatigue state, possibly reflecting different fatigue-induced alterations of HRV
      pattern.

PMID- 23951199
TI  - Supplementation with fish oil and genistein, individually or in combination,
      protects bone against the adverse effects of methotrexate chemotherapy in rats.
AB  - Cancer chemotherapy has been shown to induce long-term skeletal side effects such
      as osteoporosis and fractures; however, there are no preventative treatments.
      This study investigated the damaging effects of anti-metabolite methotrexate
      (MTX) subcutaneous injections (0.75 mg/kg BW) for five days and the potential
      protective benefits of daily oral gavage of fish oil at 0.5 mL/100 g BW
      (containing 375 mg of n-3 PUFA/100 g BW), genistein (2 mg/100 g BW), or their
      combination in young adult rats. MTX treatment alone significantly reduced
      primary spongiosa height and secondary spongiosa trabecular bone volume. Bone
      marrow stromal cells from the treated rats showed a significant reduction in
      osteogenic differentiation but an increase in adipogenesis ex vivo. Consistently,
      stromal cells had significantly higher mRNA levels of adipogenesis-related
      proliferator activator activated receptor-gamma (PPAR-gamma) and fatty acid
      binding protein (FABP4). MTX significantly increased the numbers of bone
      resorbing osteoclasts and marrow osteoclast precursor cell pool while
      significantly enhancing the mRNA expression of receptor activator for nuclear
      factor kappa B ligand (RANKL), the RANKL/osteoprotegerin (OPG) ratio, interleukin
      6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in the bone. Supplementary
      treatment with fish oil and/or genistein significantly preserved trabecular bone
      volume and osteogenesis but suppressed MTX-induced adipogenesis and increases in
      osteoclast numbers and pro-osteoclastogenic cytokine expression. Thus, Fish oil
      and/or genistein supplementation during MTX treatment enabled not only
      preservation of osteogenic differentiation, osteoblast number and bone volume,
      but also prevention of MTX treatment-induced increases in bone marrow adiposity,
      osteoclastogenic cytokine expression and osteoclast formation, and thus bone
      loss. 

PMID- 23951200
TI  - The impact of adult vitamin D deficiency on behaviour and brain function in male
      Sprague-Dawley rats.
AB  - BACKGROUND: Vitamin D deficiency is common in the adult population, and this has
      been linked to depression and cognitive outcomes in clinical populations. The aim
      of this study was to investigate the effects of adult vitamin D (AVD) deficiency
      on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague
      Dawley rats. METHODS: Ten-week old male Sprague-Dawley rats were fed a control or
      vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We
      first examined a range of behavioural domains including locomotion, exploration,
      anxiety, social behaviour, learned helplessness, sensorimotor gating, and
      nociception. We then assessed locomotor response to the psychomimetic drugs,
      amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice
      serial reaction time task (5C-SRT) and the 5 choice continuous performance task
      (5C-CPT) and, in a separate cohort, working memory was assessed using the delay
      match to sample (DMTS) task. We also examined excitatory and inhibitory
      neurotransmitters in prefrontal cortex and striatum. RESULTS: AVD-deficient rats
      were deficient in vitamin D3 (<10 nM) and had normal calcium and phosphate levels
      after 8-10 weeks on the diet. Overall, AVD deficiency was not associated with an
      altered phenotype across the range of behavioural domains tested. On the 5C-SRT
      AVD-deficient rats made more premature responses and more head entries during
      longer inter-trial intervals (ITI) than control rats. On the 5C-CPT AVD-deficient
      rats took longer to make false alarm (FA) responses than control rats. AVD
      deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA
      within the striatum. CONCLUSIONS: AVD-deficient rats exhibited no major
      impairments in any of the behavioural domains tested. Impairments in premature
      responses in AVD-deficient rats may indicate that these animals have specific
      alterations in striatal systems governing compulsive or reward-seeking behaviour.

PMID- 23951201
TI  - Bone marrow aspiration concentrate and platelet rich plasma for osteochondral
      repair in a porcine osteochondral defect model.
AB  - BACKGROUND: Bone marrow aspiration concentrate (BMAC) may possess a high potency
      for cartilage and osseous defect healing because it contains stem cells and
      multiple growth factors. Alternatively, platelet rich plasma (PRP), which
      contains a cocktail of multiple growth factors released from enriched activated
      thrombocytes may potentially stimulate the mesenchymal stem cells (MSCs) in bone
      marrow to proliferate and differentiate. METHODS: A critical size osteochondral
      defect (10*6 mm) in both medial femoral condyles was created in 14 Goettinger
      mini-pigs. All animals were randomized into the following four groups: biphasic
      scaffold alone (TRUFIT BGS, Smith & Nephew, USA), scaffold with PRP, scaffold
      with BMAC and scaffold in combination with BMAC and PRP. After 26 weeks all
      animals were euthanized and histological slides were cut, stained and evaluated
      using a histological score and immunohistochemistry. RESULTS: The thrombocyte
      number was significantly increased (p = 0.049) in PRP compared to whole blood. In
      addition the concentration of the measured growth factors in PRP such as BMP-2,
      BMP-7, VEGF, TGF-beta1 and PDGF were significantly increased when compared to
      whole blood (p<0.05). In the defects of the therapy groups areas of chondrogenic
      tissue were present, which stained blue with toluidine blue and positively for
      collagen type II. Adding BMAC or PRP in a biphasic scaffold led to a significant
      improvement of the histological score compared to the control group, but the
      combination of BMAC and PRP did not further enhance the histological score.
      CONCLUSIONS: The clinical application of BMAC or PRP in osteochondral defect
      healing is attractive because of their autologous origin and cost-effectiveness.
      Adding either PRP or BMAC to a biphasic scaffold led to a significantly better
      healing of osteochondral defects compared with the control group. However, the
      combination of both therapies did not further enhance healing.

PMID- 23951202
TI  - Bilateral bi-cephalic tDCS with two active electrodes of the same polarity
      modulates bilateral cognitive processes differentially [corrected].
AB  - Transcranial direct current stimulation (tDCS) is an innovative method to explore
      the causal structure-function relationship of brain areas. We investigated the
      specificity of bilateral bi-cephalic tDCS with two active electrodes of the same
      polarity (e.g., cathodal on both hemispheres) applied to intraparietal cortices
      bilaterally using a combined between- and within-task approach. Regarding between
      task specificity, we observed that bilateral bi-cephalic tDCS affected a
      numerical (mental addition) but not a control task (colour word Stroop),
      indicating a specific influence of tDCS on numerical but not on domain general
      cognitive processes associated with the bilateral IPS. In particular, the
      numerical effect of distractor distance was more pronounced under cathodal than
      under anodal stimulation. Moreover, with respect to within-task specificity we
      only found the numerical distractor distance effect in mental addition to be
      modulated by direct current stimulation, whereas the effect of target identity
      was not affected. This implies a differential influence of bilateral bi-cephalic
      tDCS on the recruitment of different processing components within the same task
      (number magnitude processing vs. recognition of familiarity). In sum, this first
      successful application of bilateral bi-cephalic tDCS with two active electrodes
      of the same polarity in numerical cognition research corroborates the specific
      proposition of the Triple Code Model that number magnitude information is
      represented bilaterally in the intraparietal cortices. 

PMID- 23951203
TI  - Recalibration of the multisensory temporal window of integration results from
      changing task demands.
AB  - The notion of the temporal window of integration, when applied in a multisensory
      context, refers to the breadth of the interval across which the brain perceives
      two stimuli from different sensory modalities as synchronous. It maintains a
      unitary perception of multisensory events despite physical and biophysical timing
      differences between the senses. The boundaries of the window can be influenced by
      attention and past sensory experience. Here we examined whether task demands
      could also influence the multisensory temporal window of integration. We varied
      the stimulus onset asynchrony between simple, short-lasting auditory and visual
      stimuli while participants performed two tasks in separate blocks: a temporal
      order judgment task that required the discrimination of subtle auditory-visual
      asynchronies, and a reaction time task to the first incoming stimulus
      irrespective of its sensory modality. We defined the temporal window of
      integration as the range of stimulus onset asynchronies where performance was
      below 75% in the temporal order judgment task, as well as the range of stimulus
      onset asynchronies where responses showed multisensory facilitation (race model
      violation) in the reaction time task. In 5 of 11 participants, we observed audio
      visual stimulus onset asynchronies where reaction time was significantly
      accelerated (indicating successful integration in this task) while performance
      was accurate in the temporal order judgment task (indicating successful
      segregation in that task). This dissociation suggests that in some participants,
      the boundaries of the temporal window of integration can adaptively recalibrate
      in order to optimize performance according to specific task demands. 

PMID- 23951204
TI  - Oroxylin A accelerates liver regeneration in CCl4-induced acute liver injury
      mice.
AB  - INTRODUCTION: Based on the previous research that oroxylin A can suppress
      inflammation, we investigated the hepatoprotective role of oroxylin A against
      CCl4-induced liver damage in mice and then studied the possible alteration of the
      activities of cytokine signaling participating in liver regeneration. Wild type
      (WT) mice were orally administrated with oroxylin A (60 mg/kg) for 4 days after
      CCl4 injection, the anti-inflammatory effects of oroxylin A were assessed
      directly by hepatic histology and indirectly by measuring serum levels of
      aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Albumin.
      Proliferating cell nuclear antigen (PCNA) staining was performed to evaluate the
      role of oroxylin A in promoting hepatocyte proliferation. Serum IL-1beta, TNF
      alpha, IL-6 and IL-1Ra levels were measured by enzyme-linked immunosorbent assay
      (ELISA) and liver HGF, EGF, TNF-alpha, IL-6, IL-1Ra and IL-1beta gene expression
      was determined by quantitative real-time PCR. The data indicated that the IL-6
      and TNF-alpha mRNA of oroxylin A administered group significantly increased
      higher than the control within 12 hours after CCl4 treatment. Meanwhile, oroxylin
      A significantly enhanced the expression of IL-1Ra at the early phase, which
      indicated that oroxylin A could facilitate the initiating events in liver
      regeneration by increasing IL-1Ra which acts as an Acute-Phase Protein (APP). In
      addition, a lethal CCl4-induced acute liver failure model offers a survival
      benefit in oroxylin A treated WT mice. However, oroxylin A could not
      significantly improve the percent survival of IL-1RI-/- mice with a lethal CCl4
      induced acute liver failure. CONCLUSIONS: Our study confirmed that oroxylin A
      could strongly promote liver structural remodeling and functional recovery
      through IL-1Ra/IL-1RI signaling pathway. All these results support the
      possibility of oroxylin A being a therapeutic candidate for acute liver injury.

PMID- 23951205
TI  - Decoding the dopamine signal in macaque prefrontal cortex: a simulation study
      using the Cx3Dp simulator.
AB  - Dopamine transmission in the prefrontal cortex plays an important role in reward
      based learning, working memory and attention. Dopamine is thought to be released
      non-synaptically into the extracellular space and to reach distant receptors
      through diffusion. This simulation study examines how the dopamine signal might
      be decoded by the recipient neuron. The simulation was based on parameters from
      the literature and on our own quantified, structural data from macaque prefrontal
      area 10. The change in extracellular dopamine concentration was estimated at
      different distances from release sites and related to the affinity of the
      dopamine receptors. Due to the sparse and random distribution of release sites, a
      transient heterogeneous pattern of dopamine concentration emerges. Our simulation
      predicts, however, that at any point in the simulation volume there is sufficient
      dopamine to bind and activate high-affinity dopamine receptors. We propose that
      dopamine is broadcast to its distant receptors and any change from the local
      baseline concentration might be decoded by a transient change in the binding
      probability of dopamine receptors. Dopamine could thus provide a graduated
      'teaching' signal to reinforce concurrently active synapses and cell assemblies.
      In conditions of highly reduced or highly elevated dopamine levels the
      simulations predict that relative changes in the dopamine signal can no longer be
      decoded, which might explain why cognitive deficits are observed in patients with
      Parkinson's disease, or induced through drugs blocking dopamine reuptake. 

PMID- 23951206
TI  - Genomic and proteomic analysis of Schizaphis graminum reveals cyclophilin
      proteins are involved in the transmission of cereal yellow dwarf virus.
AB  - Yellow dwarf viruses cause the most economically important virus diseases of
      cereal crops worldwide and are transmitted by aphid vectors. The identification
      of aphid genes and proteins mediating virus transmission is critical to develop
      agriculturally sustainable virus management practices and to understand viral
      strategies for circulative movement in all insect vectors. Two cyclophilin B
      proteins, S28 and S29, were identified previously in populations of
      Schizaphisgraminum that differed in their ability to transmit the RPV strain of
      Cereal yellow dwarf virus (CYDV-RPV). The presence of S29 was correlated with F2
      genotypes that were efficient virus transmitters. The present study revealed the
      two proteins were isoforms, and a single amino acid change distinguished S28 and
      S29. The distribution of the two alleles was determined in 12 F2 genotypes
      segregating for CYDV-RPV transmission capacity and in 11 genetically independent,
      field-collected S. graminum biotypes. Transmission efficiency for CYDV-RPV was
      determined in all genotypes and biotypes. The S29 isoform was present in all
      genotypes or biotypes that efficiently transmit CYDV-RPV and more specifically in
      genotypes that efficiently transport virus across the hindgut. We confirmed a
      direct interaction between CYDV-RPV and both S28 and S29 using purified virus and
      bacterially expressed, his-tagged S28 and S29 proteins. Importantly, S29 failed
      to interact with a closely related virus that is transported across the aphid
      midgut. We tested for in vivo interactions using an aphid-virus co
      immunoprecipitation strategy coupled with a bottom-up LC-MS/MS analysis using a Q
      Exactive mass spectrometer. This analysis enabled us to identify a third
      cyclophilin protein, cyclophilin A, interacting directly or in complex with
      purified CYDV-RPV. Taken together, these data provide evidence that both
      cyclophilin A and B interact with CYDV-RPV, and these interactions may be
      important but not sufficient to mediate virus transport from the hindgut lumen
      into the hemocoel. 

PMID- 23951208
TI  - Sex-biased dispersal at different geographical scales in a cooperative breeder
      from fragmented rainforest.
AB  - Dispersal affects both social behavior and population structure and is therefore
      a key determinant of long-term population persistence. However, dispersal
      strategies and responses to spatial habitat alteration may differ between sexes.
      Here we analyzed spatial and temporal variation in ten polymorphic microsatellite
      DNA loci of male and female Cabanis's greenbuls (Phyllastrephuscabanisi), a
      cooperative breeder of Afrotropical rainforest, to quantify rates of gene flow
      and fine-grained genetic structuring within and among fragmented populations. We
      found genetic evidence for female-biased dispersal at small spatial scales, but
      not at the landscape level. Local autocorrelation analysis provided evidence of
      positive genetic structure within 300 m distance ranges, which is consistent with
      behavioral observations of short-distance natal dispersal. At a landscape scale,
      individual-based autocorrelation values decreased over time while levels of
      admixture increased, possibly indicating increased gene flow over the past
      decade. 

PMID- 23951207
TI  - Dissociation of increases in PGC-1alpha and its regulators from exercise
      intensity and muscle activation following acute exercise.
AB  - Muscle activation as well as changes in peroxisome proliferator-activated
      receptor gamma coactivator 1 alpha (PGC-1alpha) following high-intensity interval
      exercise (HIIE) were examined in young healthy men (n  = 8; age, 21.9+/-2.2 yrs;
      VO2peak, 53.1+/-6.4 ml/min/kg; peak work rate, 317+/-23.5 watts). On each of 3
      visits HIIE was performed on a cycle ergometer at a target intensity of 73, 100,
      or 133% of peak work rate. Muscle biopsies were taken at rest and three hours
      after each exercise condition. Total work was not different between conditions
      (~730 kJ) while average power output (73%, 237+/-21; 100%, 323+/-26; 133%, 384+/
      35 watts) and EMG derived muscle activation (73%, 1262+/-605; 100%, 2089+/-737;
      133%, 3029+/-1206 total integrated EMG per interval) increased in an intensity
      dependent fashion. PGC-1alpha mRNA was elevated after all three conditions
      (p<0.05), with a greater increase observed following the 100% condition (~9 fold,
      p<0.05) compared to both the 73 and 133% conditions (~4 fold). When expressed
      relative to muscle activation, the increase in PGC-1alpha mRNA for the 133%
      condition was less than that for the 73 and 100% conditions (p<0.05). SIRT1 mRNA
      was also elevated after all three conditions (~1.4 fold, p<0.05), with no
      difference between conditions. These findings suggest that intensity-dependent
      increases in PGC-1alpha mRNA following submaximal exercise are largely due to
      increases in muscle recruitment. As well, the blunted response of PGC-1alpha mRNA
      expression following supramaximal exercise may indicate that signalling mediated
      activation of PGC-1alpha may also be blunted. We also indentify that increases in
      PDK4, SIRT1, and RIP140 mRNA following acute exercise are dissociated from
      exercise intensity and muscle activation, while increases in EGR1 are augmented
      with supramaximal HIIE (p<0.05). 

PMID- 23951209
TI  - Cytoskeletal regulation dominates temperature-sensitive proteomic changes of
      hibernation in forebrain of 13-lined ground squirrels.
AB  - 13-lined ground squirrels, Ictidomys tridecemlineatus, are obligate hibernators
      that transition annually between summer homeothermy and winter heterothermy -
      wherein they exploit episodic torpor bouts. Despite cerebral ischemia during
      torpor and rapid reperfusion during arousal, hibernator brains resist damage and
      the animals emerge neurologically intact each spring. We hypothesized that
      protein changes in the brain underlie winter neuroprotection. To identify
      candidate proteins, we applied a sensitive 2D gel electrophoresis method to
      quantify protein differences among forebrain extracts prepared from ground
      squirrels in two summer, four winter and fall transition states. Proteins that
      differed among groups were identified using LC-MS/MS. Only 84 protein spots
      varied significantly among the defined states of hibernation. Protein changes in
      the forebrain proteome fell largely into two reciprocal patterns with a strong
      body temperature dependence. The importance of body temperature was tested in
      animals from the fall; these fall animals use torpor sporadically with body
      temperatures mirroring ambient temperatures between 4 and 21 degrees C as they
      navigate the transition between summer homeothermy and winter heterothermy.
      Unlike cold-torpid fall ground squirrels, warm-torpid individuals strongly
      resembled the homeotherms, indicating that the changes observed in torpid
      hibernators are defined by body temperature, not torpor per se. Metabolic enzymes
      were largely unchanged despite varied metabolic activity across annual and torpor
      arousal cycles. Instead, the majority of the observed changes were cytoskeletal
      proteins and their regulators. While cytoskeletal structural proteins tended to
      differ seasonally, i.e., between summer homeothermy and winter heterothermy,
      their regulatory proteins were more strongly affected by body temperature.
      Changes in the abundance of various isoforms of the microtubule assembly and
      disassembly regulatory proteins dihydropyrimidinase-related protein and stathmin
      suggested mechanisms for rapid cytoskeletal reorganization on return to euthermy
      during torpor-arousal cycles. 

PMID- 23951211
TI  - Abiotic racemization kinetics of amino acids in marine sediments.
AB  - The ratios of d- versus l-amino acids can be used to infer the sources and
      composition of sedimentary organic matter. Such inferences, however, rely on
      knowing the rates at which amino acids in sedimentary organic matter racemize
      abiotically between the d- and the l-forms. Based on a heating experiment, we
      report kinetic parameters for racemization of aspartic acid, glutamic acid,
      serine, and alanine in bulk sediment from Aarhus Bay, Denmark, taken from the
      surface, 30 cm, and 340 cm depth below seafloor. Extrapolation to a typical cold
      deep sea sediment temperature of 3 degrees C suggests racemization rate constants
      of 0.50*10(-5)-11*10(-5) yr(-1). These results can be used in conjunction with
      measurements of sediment age to predict the ratio of d:l amino acids due solely
      to abiotic racemization of the source material, deviations from which can
      indicate the abundance and turnover of active microbial populations. 

PMID- 23951210
TI  - Impaired blood dendritic cell numbers and functions after aneurysmal subarachnoid
      hemorrhage.
AB  - PREVIOUS PRESENTATION: Portions of this study were presented at the Annual
      Congress of Societe Francaise d'Anesthesie et de Reanimation in Paris, September
      2012. BACKGROUND: Toll-like receptor (TLR) agonists are promising therapy for the
      prevention of nosocomial infections in critical ill patients. We aimed to analyze
      the TLR-reactivity of circulating dendritic cells (DC) as assessed by cytokine
      production after an ex vivo challenge with TLR agonists in aneurysmal
      subarachnoid hemorrhage (SAH) patients. METHODS AND FINDINGS: A single-center
      prospective observational study took place in one intensive care unit of a
      teaching hospital. Blood samples were harvested on days 2, 5 and 10 in 21 severe
      SAH patients requiring mechanical ventilation and 17 healthy controls. DC
      production of cytokines (Tumour Necrosis Factor, TNF-alpha; Interleukin, IL-12;
      and Interferon, IFN-alpha) was assessed by intracellular immunostaining on TLR-3,
      4, 7/8 and 9 stimulations. SAH patients had decreased numbers of blood myeloid
      (mDCs) and plasmacytoid DCs (pDCs) on days 2, 5 and 10. Compared with the healthy
      controls, the frequency of mDCs producing TNF-alpha after TLR-3 stimulation was
      decreased in the SAH patients. The frequency of myeloid DCs producing IL-12 after
      TLR-3 and 4 stimulations was also decreased in the SAH patients. In contrast, the
      mDCs response to TLR-7/8 was not impaired in the SAH patients. The frequency of
      pDCs producing TNF-alpha(+) and IFN-alpha(+) on TLR-7/8 stimulation were reduced
      at all of the tested times in the SAH patients, whereas reactivity to TLR-9 was
      preserved. On day 2, the pDCs from non-survivor patients (n=8) had a decreased
      ability to produce IFN-alpha on TLR-9 stimulation compared with the survivors.
      CONCLUSIONS: These data suggest functional abnormalities of circulating pDCs and
      mDCs that could be important for immunomodulation after SAH.

PMID- 23951212
TI  - Inhibitory peptide of mitochondrial MU-calpain protects against photoreceptor
      degeneration in rhodopsin transgenic S334ter and P23H rats.
AB  - Mitochondrial MU-calpain and apoptosis-inducing factor (AIF)-dependent
      photoreceptor cell death has been seen in several rat and mouse models of
      retinitis pigmentosa (RP). Previously, we demonstrated that the specific peptide
      inhibitor of mitochondrial MU-calpain, Tat-uCL, protected against retinal
      degeneration following intravitreal injection or topical eye-drop application in
      Mertk gene-mutated Royal College of Surgeons rats, one of the animal models of
      RP. Because of the high rate of rhodopsin mutations in RP patients, the present
      study was performed to confirm the protective effects of Tat-uCL against retinal
      degeneration in rhodopsin transgenic S334ter and P23H rats. We examined the
      effects of intravitreal injection or topical application of the peptide on
      retinal degeneration in S334ter and P23H rats by terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling (TUNEL) assay, electroretinogram
      (ERG), immunohistochemistry for AIF, and histological staining. In S334ter rats,
      we found that intravitreal injection or topical application of the peptide
      prevented photoreceptor cell death from postnatal (PN) 15 to 18 days, the time of
      early-stage retinal degeneration. Topical application of the peptide also delayed
      attenuation of ERG responses from PN 28 to 56 days. In P23H rats, topical
      application of the peptide protected against photoreceptor cell death and nuclear
      translocation of AIF on PN 30, 40, and 50 days, as the primary stages of
      degeneration. We observed that topical application of the peptide inhibited the
      thinning of the outer nuclear layer and delayed ERG attenuations from PN 30 to 90
      days. Our results demonstrate that the mitochondrial MU-calpain and AIF pathway
      is involved in early-stage retinal degeneration in rhodopsin transgenic S334ter
      and P23H rats, and inhibition of this pathway shows curative potential for
      rhodopsin mutation-caused RP. 

PMID- 23951213
TI  - The essential role of the Deinococcus radiodurans ssb gene in cell survival and
      radiation tolerance.
AB  - Recent evidence has implicated single-stranded DNA-binding protein (SSB)
      expression level as an important factor in microbial radiation resistance. The
      genome of the extremely radiation resistant bacterium Deinococcus radiodurans
      contains genes for two SSB homologs: the homodimeric, canonical Ssb, encoded by
      the gene ssb, and a novel pentameric protein encoded by the gene ddrB. ddrB is
      highly induced upon exposure to radiation, and deletions result in decreased
      radiation-resistance, suggesting an integral role of the protein in the extreme
      resistance exhibited by this organism. Although expression of ssb is also induced
      after irradiation, Ssb is thought to be involved primarily in replication. In
      this study, we demonstrate that Ssb in D. radiodurans is essential for cell
      survival. The lethality of an ssb deletion cannot be complemented by providing
      ddrB in trans. In addition, the radiation-sensitive phenotype conferred by a ddrB
      deletion is not alleviated by providing ssb in trans. By altering expression of
      the ssb gene, we also show that lower levels of transcription are required for
      optimal growth than are necessary for high radiation resistance. When expression
      is reduced to that of E. coli, ionizing radiation resistance is similarly
      reduced. UV resistance is also decreased under low ssb transcript levels where
      growth is unimpaired. These results indicate that the expression of ssb is a key
      component of both normal cellular metabolism as well as pathways responsible for
      the high radiation tolerance of D. radiodurans. 

PMID- 23951214
TI  - Functional polymorphisms in FAS/FASL system increase the risk of neuroblastoma in
      Chinese population.
AB  - The FAS and FASL system plays a substantial role in apoptosis and immune escape
      of cells. Three polymorphisms located in the promoter regions of FAS (-1377G/A
      and -670A/G) and FASL (-844T/C) have been shown to alter the transcriptional
      activity of the genes, respectively. This study was conducted to evaluate the
      effects of these polymorphisms on the susceptibility of neuroblastoma in the
      Chinese population. A total of 203 patients with neuroblastoma and 411 controls
      were recruited in this case-control study. Polymerase chain reaction-based
      restriction fragment length polymorphism (PCR-RFLP) was applied for genotyping.
      Unconditional logistic regression was used to estimate cancer risk by calculating
      odds ratios (ORs) and their 95% confidence intervals (95% CIs). It was observed
      that significantly increased risks of neuroblastoma associated with FAS -1377G/A
      and FASL -844T/C polymorphisms, with ORs equal to 1.55 (95% CI, 1.10-2.20) for
      FAS -1377 A allele and 2.90 (95% CI, 2.04-4.12) for FASL -844CC genotype carriers
      compared with non-carriers, respectively. However, no association was found
      between the polymorphisms of FAS -670A/G and risk of neuroblastoma. In addition,
      the cumulative effect of FAS and FASL polymorphisms on risk of neuroblastoma was
      observed (P for trend = 2.502*10(-10)), with OR for the carriers of both FAS 
      1377A allele and FASL -844CC genotypes equaled to 3.95 (95% CI, 2.40-6.51). This
      work reveals that polymorphisms of FAS -1377G/A and FASL -844T/C but not FAS 
      670A/G are associated with risk of neuroblastoma in Chinese. These findings
      support the hypothesis that genetic polymorphism in FAS/FASL death system may
      influence individual susceptibility to neuroblastoma. 

PMID- 23951215
TI  - Prefabrication of 3D cartilage contructs: towards a tissue engineered auricle--a
      model tested in rabbits.
AB  - The reconstruction of an auricle for congenital deformity or following trauma
      remains one of the greatest challenges in reconstructive surgery. Tissue
      engineered (TE) three-dimensional (3D) cartilage constructs have proven to be a
      promising option, but problems remain with regard to cell vitality in large cell
      constructs. The supply of nutrients and oxygen is limited because cultured
      cartilage is not vascular integrated due to missing perichondrium. The
      consequence is necrosis and thus a loss of form stability. The micro-surgical
      implantation of an arteriovenous loop represents a reliable technology for
      neovascularization, and thus vascular integration, of three-dimensional (3D)
      cultivated cell constructs. Auricular cartilage biopsies were obtained from 15
      rabbits and seeded in 3D scaffolds made from polycaprolactone-based polyurethane
      in the shape and size of a human auricle. These cartilage cell constructs were
      implanted subcutaneously into a skin flap (15 * 8 cm) and neovascularized by
      means of vascular loops implanted micro-surgically. They were then totally
      enhanced as 3D tissue and freely re-implanted in-situ through microsurgery.
      Neovascularization in the prefabricated flap and cultured cartilage construct was
      analyzed by microangiography. After explantation, the specimens were examined by
      histological and immunohistochemical methods. Cultivated 3D cartilage cell
      constructs with implanted vascular pedicle promoted the formation of engineered
      cartilaginous tissue within the scaffold in vivo. The auricles contained
      cartilage-specific extracellular matrix (ECM) components, such as GAGs and
      collagen even in the center oft the constructs. In contrast, in cultivated 3D
      cartilage cell constructs without vascular pedicle, ECM distribution was only
      detectable on the surface compared to constructs with vascular pedicle. We
      demonstrated, that the 3D flaps could be freely transplanted. On a
      microangiographic level it was evident that all the skin flaps and the implanted
      cultivated constructs were well neovascularized. The presented method is
      suggested as a promising alternative towards clinical application of engineered
      cartilaginous tissue for plastic and reconstructive surgery.

PMID- 23951216
TI  - Serum lipoprotein(a) positively correlates with coronary artery calcification in
      low-risk chinese han patients: a study from a single center.
AB  - BACKGROUND: Elevated plasma levels of lipoprotein(a) (Lp(a)) and a higher degree
      of coronary artery calcification (CAC) are both considered to be risk factors for
      atherosclerosis. However, previous studies have demonstrated that the
      relationship between Lp(a) levels and the degree of CAC indicates significant
      heterogeneity that may be due to varying ethnicities. The purpose of this study
      was to examine the predictive power of Lp(a) for CAC as measured by multidetector
      computed tomography (MDCT) in the Han ethnic group of China. METHODS: A total of
      1082 subjects were recruited in this study. The patients were divided into four
      groups: patients without hypertension or diabetes were group 1, patients with
      hypertension were group 2, patients with diabetes were group 3 and patients with
      both hypertension and diabetes were group 4. CAC score (CACs), lipid profiles
      (Lp(a), LDL, HDL, TG, TC), HbA1C, glucose, personal health history and body
      morphology were measured in all participants. The predictive power of Lp(a) for
      calcified atherosclerotic plaque was determined by correlations and ordinal
      logistic regression. RESULTS: There was no significant difference in the CACs
      between group 2 and group 3 (z = 1.790, p = 0.736), and there were significant
      differences among the other groups. However, there was no significant difference
      in the total Lp(a) among the 4 groups (chi(2) = 0.649, p = 0.885). Only In group
      1, Lp(a) was a statistically significant predictor of the presence of calcified
      coronary plaque using ordinal logistic regression. CONCLUSIONS: Levels of Lp(a)
      positively correlate with CACs among Chinese Han people who are without diabetes
      and hypertension, suggesting that Lp(a) may be an important risk factor for the
      presence of calcified atheromas.

PMID- 23951217
TI  - Plasma asymmetric dimethylarginine and adverse events in patients with atrial
      fibrillation referred for coronary angiogram.
AB  - OBJECTIVES: Elevated plasma levels of asymmetric dimethylarginine (ADMA) have
      been reported to be associated with endothelial dysfunction, inflammation, and
      oxidative stress in multiple cardiovascular diseases. This study aimed to
      investigate whether ADMA was a predictor of clinical outcomes in atrial
      fibrillation (AF). METHODS AND RESULTS: From 2006-2009, 990 individuals were
      referred to our institution for coronary angiography. Among these patients, 141
      subjects with a diagnosis of AF, including 52 paroxysmal AF (PAF) and 89 non
      paroxysmal AF (non-PAF) patients, were identified as the study population. Plasma
      ADMA levels were measured. An adverse event was defined as the occurrence of
      ischemic stroke or cardiovascular death. The ADMA levels were higher in AF than
      non-AF patients (0.50 +/- 0.13 versus 0.45 +/- 0.07 umol/L; p<0.001). Besides,
      non-PAF patients had higher ADMA levels than PAF patients (0.52 +/- 0.15 versus
      0.48 +/- 0.08 umol/L; p<0.001). During the follow-up of 30.7+/-14.4 months, 21
      patients (14.9%) experienced adverse events, including cardiovascular death in 7
      patients and ischemic stroke in 14. ADMA level, CHA2DS2-VASc score, and left
      atrial diameter were independent predictors of adverse events in the multivariate
      analysis. At a cutoff-value of 0.55 umol/L, the Kaplan-Meier survival analysis
      showed that patients with a high ADMA level had a higher event rate during the
      follow-up period. CONCLUSIONS: A higher level of ADMA was a risk factor of
      adverse events in AF patients, which was independent from the CHA2DS2-VASc score.
      It deserves to further study whether ADMA could potentially refine the clinical
      risk stratification in AF.

PMID- 23951218
TI  - Individual cell based traits obtained by scanning flow-cytometry show selection
      by biotic and abiotic environmental factors during a phytoplankton spring bloom.
AB  - In ecology and evolution, the primary challenge in understanding the processes
      that shape biodiversity is to assess the relationship between the phenotypic
      traits of organisms and the environment. Here we tested for selection on physio
      morphological traits measured by scanning flow-cytometry at the individual level
      in phytoplankton communities under a temporally changing biotic and abiotic
      environment. Our aim was to study how high-frequency temporal changes in the
      environment influence biodiversity dynamics in a natural community. We focused on
      a spring bloom in Lake Zurich (Switzerland), characterized by rapid changes in
      phytoplankton, water conditions, nutrients and grazing (mainly mediated by
      herbivore ciliates). We described bloom dynamics in terms of taxonomic and trait
      based diversity and found that diversity dynamics of trait-based groups were more
      pronounced than those of identified phytoplankton taxa. We characterized the
      linkage between measured phytoplankton traits, abiotic environmental factors and
      abundance of the main grazers and observed weak but significant correlations
      between changing abiotic and biotic conditions and measured size-related and
      fluorescence-related traits. We tested for deviations in observed community-wide
      distributions of focal traits from random patterns and found evidence for both
      clustering and even spacing of traits, occurring sporadically over the time
      series. Patterns were consistent with environmental filtering and phenotypic
      divergence under herbivore pressure, respectively. Size-related traits showed
      significant even spacing during the peak of herbivore abundance, suggesting that
      morphology-related traits were under selection from grazing. Pigment distribution
      within cells and colonies appeared instead to be associated with acclimation to
      temperature and water chemistry. We found support for trade-offs among grazing
      resistance and environmental tolerance traits, as well as for substantial periods
      of dynamics in which our measured traits were not under selection. 

PMID- 23951219
TI  - Reducing the socio-economic status achievement gap at University by promoting
      mastery-oriented assessment.
AB  - In spite of official intentions to reduce inequalities at University, students'
      socio-economic status (SES) is still a major determinant of academic success. The
      literature on the dual function of University suggests that University serves not
      only an educational function (i.e., to improve students' learning), but also a
      selection function (i.e., to compare people, and orient them towards different
      positions in society). Because current assessment practices focus on the
      selection more than on the educational function, their characteristics fit better
      with norms and values shared by dominant high-status groups and may favour high
      SES students over low-SES students in terms of performances. A focus on the
      educational function (i.e., mastery goals), instead, may support low-SES
      students' achievement, but empirical evidence is currently lacking. The present
      research set out to provide such evidence and tested, in two field studies and a
      randomised field experiment, the hypothesis that focusing on University's
      educational function rather than on its selection function may reduce the SES
      achievement gap. Results showed that a focus on learning, mastery-oriented goals
      in the assessment process reduced the SES achievement gap at University. For the
      first time, empirical data support the idea that low-SES students can perform as
      well as high-SES students if they are led to understand assessment as part of the
      learning process, a way to reach mastery goals, rather than as a way to compare
      students to each other and select the best of them, resulting in performance
      goals. This research thus provides a theoretical framework to understand the
      differential effects of assessment on the achievement of high and low-SES
      students, and paves the way toward the implementation of novel, theory-driven
      interventions to reduce the SES-based achievement gap at University. 

PMID- 23951220
TI  - Chronic ethanol consumption disrupts the core molecular clock and diurnal rhythms
      of metabolic genes in the liver without affecting the suprachiasmatic nucleus.
AB  - Chronic ethanol consumption disrupts several metabolic pathways including beta
      oxidation and lipid biosynthesis, facilitating the development of alcoholic fatty
      liver disease. Many of these same metabolic pathways are directly regulated by
      cell autonomous circadian clocks, and recent studies suggest that disruption of
      daily rhythms in metabolism contributes to multiple common cardiometabolic
      diseases (including non-alcoholic fatty liver disease). However, it is not known
      whether ethanol disrupts the core molecular clock in the liver, nor whether this,
      in turn, alters rhythms in lipid metabolism. Herein, we tested the hypothesis
      that chronic ethanol consumption disrupts the molecular circadian clock in the
      liver and potentially changes the diurnal expression patterns of lipid metabolism
      genes. Consistent with previous studies, male C57BL/6J mice fed an ethanol
      containing diet exhibited higher levels of liver triglycerides compared to
      control mice, indicating hepatic steatosis. Further, the diurnal oscillations of
      core clock genes (Bmal1, Clock, Cry1, Cry2, Per1, and Per2) and clock-controlled
      genes (Dbp, Hlf, Nocturnin, Npas2, Rev-erbalpha, and Tef) were altered in livers
      from ethanol-fed mice. In contrast, ethanol had only minor effects on the
      expression of core clock genes in the suprachiasmatic nucleus (SCN). These
      results were confirmed in Per2(Luciferase) knock-in mice, in which ethanol
      induced a phase advance in PER2::LUC bioluminescence oscillations in liver, but
      not SCN. Further, there was greater variability in the phase of PER2::LUC
      oscillations in livers from ethanol-fed mice. Ethanol consumption also affected
      the diurnal oscillations of metabolic genes, including Adh1, Cpt1a, Cyp2e1, Pck1,
      Pdk4, Ppargc1a, Ppargc1b and Srebp1c, in the livers of C57BL/6J mice. In summary,
      chronic ethanol consumption alters the function of the circadian clock in liver.
      Importantly, these results suggest that chronic ethanol consumption, at levels
      sufficient to cause steatosis, disrupts the core hepatic clock as well as the
      diurnal rhythms of key lipid metabolism genes. 

PMID- 23951221
TI  - A masked PY-NLS in Drosophila TIS11 and its mammalian homolog tristetraprolin.
AB  - Many RNA-binding proteins (RBPs) dynamically shuttle between the nucleus and the
      cytoplasm, often exerting different functions in each compartment. Therefore, the
      nucleo-cytoplasmic distribution of RBPs has a strong impact on their activity.
      Here we describe the localization and the shuttling properties of the tandem zinc
      finger RBP dTIS11, which is the Drosophila homolog of mammalian TIS11 proteins.
      Drosophila and mammalian TIS11 proteins act as destabilizing factors in ARE
      mediated decay. At equilibrium, dTIS11 is concentrated mainly in the cytoplasm.
      We show that dTIS11 is a nucleo-cytoplasmic shuttling protein whose nuclear
      export is mediated by the exportin CRM1 through the recognition of a nuclear
      export signal (NES) located in a different region comparatively to its mammalian
      homologs. We also identify a cryptic Transportin-dependent PY nuclear
      localization signal (PY-NLS) in the tandem zinc finger region of dTIS11 and show
      that it is conserved across the TIS11 protein family. This NLS partially overlaps
      the second zinc finger ZnF2. Importantly, mutations disrupting the capacity of
      the ZnF2 to coordinate a Zinc ion unmask dTIS11 and TTP NLS and promote nuclear
      import. All together, our results indicate that the nuclear export of TIS11
      proteins is mediated by CRM1 through diverging NESs, while their nuclear import
      mechanism may rely on a highly conserved PY-NLS whose activity is negatively
      regulated by ZnF2 folding. 

PMID- 23951223
TI  - Teleconference versus face-to-face scientific peer review of grant application:
      effects on review outcomes.
AB  - Teleconferencing as a setting for scientific peer review is an attractive option
      for funding agencies, given the substantial environmental and cost savings.
      Despite this, there is a paucity of published data validating teleconference
      based peer review compared to the face-to-face process. Our aim was to conduct a
      retrospective analysis of scientific peer review data to investigate whether
      review setting has an effect on review process and outcome measures. We analyzed
      reviewer scoring data from a research program that had recently modified the
      review setting from face-to-face to a teleconference format with minimal changes
      to the overall review procedures. This analysis included approximately 1600
      applications over a 4-year period: two years of face-to-face panel meetings
      compared to two years of teleconference meetings. The average overall scientific
      merit scores, score distribution, standard deviations and reviewer inter-rater
      reliability statistics were measured, as well as reviewer demographics and length
      of time discussing applications. The data indicate that few differences are
      evident between face-to-face and teleconference settings with regard to average
      overall scientific merit score, scoring distribution, standard deviation,
      reviewer demographics or inter-rater reliability. However, some difference was
      found in the discussion time. These findings suggest that most review outcome
      measures are unaffected by review setting, which would support the trend of using
      teleconference reviews rather than face-to-face meetings. However, further
      studies are needed to assess any correlations among discussion time, application
      funding and the productivity of funded research projects. 

PMID- 23951222
TI  - De-novo design of antimicrobial peptides for plant protection.
AB  - This work describes the de-novo design of peptides that inhibit a broad range of
      plant pathogens. Four structurally different groups of peptides were developed
      that differ in size and position of their charged and hydrophobic clusters and
      were assayed for their ability to inhibit bacterial growth and fungal spore
      germination. Several peptides are highly active at concentrations between 0,1 and
      1 ug/ml against plant pathogenic bacteria, such as Pseudomonas syringae,
      Pectobacterium carotovorum, and Xanthomonas vesicatoria. Importantly, no
      hemolytic activity could be detected for these peptides at concentrations up to
      200 ug/ml. Moreover, the peptides are also active after spraying on the plant
      surface demonstrating a possible way of application. In sum, our designed
      peptides represent new antimicrobial agents and with the increasing demand for
      antimicrobial compounds for production of "healthy" food, these peptides might
      serve as templates for novel antibacterial and antifungal agents. 

PMID- 23951224
TI  - Novel extracellular PHB depolymerase from Streptomyces ascomycinicus: PHB
      copolymers degradation in acidic conditions.
AB  - The ascomycin-producer strain Streptomyces ascomycinicus has been proven to be an
      extracellular poly(R)-3-hydroxybutyrate (PHB) degrader. The fkbU gene, encoding a
      PHB depolymerase (PhaZ Sa ), has been cloned in E. coli and Rhodococcus sp. T104
      strains for gene expression. Gram-positive host Rhodococcus sp. T104 was able to
      produce and secrete to the extracellular medium an active protein form. PhaZ Sa
      was purified by two hydrophobic interaction chromatographic steps, and afterwards
      was biochemically as well as structurally characterized. The enzyme was found to
      be a monomer with a molecular mass of 48.4 kDa, and displayed highest activity at
      45 degrees C and pH 6, thus being the first PHB depolymerase from a gram-positive
      bacterium presenting an acidic pH optimum. The PHB depolymerase activity of PhaZ
      Sa was increased in the presence of divalent cations due to non-essential
      activation, and also in the presence of methyl-beta-cyclodextrin and PEG 3350.
      Protein structure was analyzed, revealing a globular shape with an alpha-beta
      hydrolase fold. The amino acids comprising the catalytic triad, Ser(131)-Asp(209)
      His(269), were identified by multiple sequence alignment, chemical modification
      of amino acids and site-directed mutagenesis. These structural results supported
      the proposal of a three-dimensional model for this depolymerase. PhaZ Sa was able
      to degrade PHB, but also demonstrated its ability to degrade films made of PHB,
      PHBV copolymers and a blend of PHB and starch (7?3 proportion wt/wt). The
      features shown by PhaZ Sa make it an interesting candidate for industrial
      applications involving PHB degradation. 

PMID- 23951225
TI  - The polyphenol oleuropein aglycone protects TgCRND8 mice against Abeta plaque
      pathology.
AB  - The claimed beneficial effects of the Mediterranean diet include prevention of
      several age-related dysfunctions including neurodegenerative diseases and
      Alzheimer-like pathology. These effects have been related to the protection
      against cognitive decline associated with aging and disease by a number of
      polyphenols found in red wine and extra virgin olive oil. The double transgenic
      TgCRND8 mice (overexpressing the Swedish and Indiana mutations in the human
      amyloid precursor protein), aged 1.5 and 4, and age-matched wild type control
      mice were used to examine in vivo the effects of 8 weeks dietary supplementation
      of oleuropein aglycone (50 mg/kg of diet), the main polyphenol found in extra
      virgin olive oil. We report here that dietary supplementation of oleuropein
      aglycone strongly improves the cognitive performance of young/middle-aged TgCRND8
      mice, a model of amyloid-beta deposition, respect to age-matched littermates with
      un-supplemented diet. Immunofluorescence analysis of cerebral tissue in
      oleuropein aglycone-fed transgenic mice showed remarkably reduced beta-amyloid
      levels and plaque deposits, which appeared less compact and "fluffy"; moreover,
      microglia migration to the plaques for phagocytosis and a remarkable reduction of
      the astrocyte reaction were evident. Finally, oleuropein aglycone-fed mice brain
      displayed an astonishingly intense autophagic reaction, as shown by the increase
      of autophagic markers expression and of lysosomal activity. Data obtained with
      cultured cells confirmed the latter evidence, suggesting mTOR regulation by
      oleuropein aglycone. Our results support, and provide mechanistic insights into,
      the beneficial effects against Alzheimer-associated neurodegeneration of a
      polyphenol enriched in the extra virgin olive oil, a major component of the
      Mediterranean diet. 

PMID- 23951226
TI  - Mutationmapper: a tool to aid the mapping of protein mutation data.
AB  - There has been a rapid increase in the amount of mutational data due to, amongst
      other things, an increase in single nucleotide polymorphism (SNP) data and the
      use of site-directed mutagenesis as a tool to help dissect out functional
      properties of proteins. Many manually curated databases have been developed to
      index point mutations but they are not sustainable with the ever-increasing
      volume of scientific literature. There have been considerable efforts in the
      automatic extraction of mutation specific information from raw text involving use
      of various text-mining approaches. However, one of the key problems is to link
      these mutations with its associated protein and to present this data in such a
      way that researchers can immediately contextualize it within a structurally
      related family of proteins. To aid this process, we have developed an application
      called MutationMapper. Point mutations are extracted from abstracts and are
      validated against protein sequences in Uniprot as far as possible. Our
      methodology differs in a fundamental way from the usual text-mining approach.
      Rather than start with abstracts, we start with protein sequences, which
      facilitates greatly the process of validating a potential point mutation
      identified in an abstract. The results are displayed as mutations mapped on to
      the protein sequence or a multiple sequence alignment. The latter enables one to
      readily pick up mutations performed at equivalent positions in related proteins.
      We demonstrate the use of MutationMapper against several examples including a
      single sequence and multiple sequence alignments. The application is available as
      a web-service at http://mutationmapper.bioch.ox.ac.uk. 

PMID- 23951227
TI  - Assessment of social support and its association to depression, self-perceived
      health and chronic diseases in elderly individuals residing in an area of poverty
      and social vulnerability in rio de janeiro city, Brazil.
AB  - OBJECTIVES: Social support (SS) influences the elderly ability to cope with the
      losses of ageing process. This study was aimed at assessing SS among elderly
      users of a primary healthcare unit in a poor and violent area of Rio de Janeiro
      City, and at verifying its association with depression, self-perceived health
      (SPH), marital status and chronic illnesses. METHODS: A cross-sectional study was
      performed based on a convenience sample of 180 individuals aged 60 years or
      older. SS was measured with part of the Brazilian version of Medical Outcomes
      Study's SS scale, and SPH and depression were assessed, respectively, through one
      question and the Brazilian version of the Structured Clinical Interview for DSM
      IV Axis I Disorders. SS medians were calculated for the categories of SPH,
      depression, marital status and chronic illnesses variables, and differences were
      evaluated with the Kruskal-Wallis and Mann-Whitney tests. Additionally, Pearson's
      chi-square test and logistic regression were employed to identify unadjusted and
      adjusted associations between SS and those variables. RESULTS: The participant's
      mean age was 73 years old, and level of education was 3 years of school education
      on average. They were predominantly females (73.3%), and non-married (55.0%).
      Among them, 74.4% perceived their SS as satisfactory, 55.0% perceived their
      health as good, 27.8% were diagnosed with major depression and 83.3% had
      hypertension. Especially for those depressed and with bad SPH, the medians of SS
      measure were much lower than for others, reaching an unsatisfactory level.
      Moreover, controlling for other factors, non-depressed individuals were more
      likely (OR = 2.32) to have satisfactory SS. CONCLUSION: in the violent and poor
      area explored in this research low SS is highly prevalent in the elderly.
      Depressed individuals are more likely to have low SS and this condition should be
      investigated in depressed elderly. The reduced scale is useful for low education
      individuals.

PMID- 23951228
TI  - Induced expression of AtLEC1 and AtLEC2 differentially promotes somatic
      embryogenesis in transgenic tobacco plants.
AB  - Arabidopsis LEAFY COTYLEDON (LEC) genes, AtLEC1 and AtLEC2, are important
      embryonic regulators that play key roles in morphogenesis and maturation phases
      during embryo development. Ectopic expression of AtLEC1 and AtLEC2 in tobacco
      caused abnormality in transgenic seedling. When transgenic seeds germinated on
      medium containing 30 uM DEX, LEC1 transgenic seedlings were ivory and fleshy,
      with unexpanded cotyledons, stubby hypocotyls, short roots and no obvious callus
      formation at the shoot meristem position. While LEC2 transgenic seedlings formed
      embryonic callus on the shoot apical meristem and somatic embryo-like structures
      emerged from the surface of the callus. When callus were transferred to hormone
      free MS0 medium more shoots were regenerated from each callus. However, shoot
      formation was not observed in LEC1 overexpressors. To investigate the mechanisms
      of LEC2 in somatic embryogenesis, we studied global gene expression by digital
      gene expression profiling analysis. The results indicated that ectopic expression
      of LEC2 genes induced accumulation of embryo-specific proteins such as seed
      storage proteins, late embryogenesis abundant (LEA) proteins, fatty acid
      biosynthetic enzymes, products of steroid biosynthesis related genes and key
      regulatory genes of the embryo development. Genes of plant-specific transcription
      factors such as NAC domain protein, AP2 and GRAS family, resistance-related as
      well as salicylic acid signaling related genes were up-regulated in LEC2
      transgenic seedlings. Ectopi c expression of LEC2 induced large number of somatic
      embryo formation and shoot regeneration but 20 d DEX induction of LEC1 is not
      sufficient to induce somatic embryogenesis and shoot formation. Our data provide
      new information to understand the mechanisms on LEC2 gene's induction of somatic
      embryogenesis. 

PMID- 23951229
TI  - Lactate modulates the activity of primary cortical neurons through a receptor
      mediated pathway.
AB  - Lactate is increasingly described as an energy substrate of the brain. Beside
      this still debated metabolic role, lactate may have other effects on brain cells.
      Here, we describe lactate as a neuromodulator, able to influence the activity of
      cortical neurons. Neuronal excitability of mouse primary neurons was monitored by
      calcium imaging. When applied in conjunction with glucose, lactate induced a
      decrease in the spontaneous calcium spiking frequency of neurons. The effect was
      reversible and concentration dependent (IC50 ~4.2 mM). To test whether lactate
      effects are dependent on energy metabolism, we applied the closely related
      substrate pyruvate (5 mM) or switched to different glucose concentrations (0.5 or
      10 mM). None of these conditions reproduced the effect of lactate. Recently, a Gi
      protein-coupled receptor for lactate called HCA1 has been introduced. To test if
      this receptor is implicated in the observed lactate sensitivity, we incubated
      cells with pertussis toxin (PTX) an inhibitor of Gi-protein. PTX prevented the
      decrease of neuronal activity by L-lactate. Moreover 3,5-dyhydroxybenzoic acid, a
      specific agonist of the HCA1 receptor, mimicked the action of lactate. This study
      indicates that lactate operates a negative feedback on neuronal activity by a
      receptor-mediated mechanism, independent from its intracellular metabolism. 

PMID- 23951230
TI  - Reconstructing the Qo site of Plasmodium falciparum bc 1 complex in the yeast
      enzyme.
AB  - The bc 1 complex of the mitochondrial respiratory chain is essential for
      Plasmodium falciparum proliferation, the causative agent of human malaria.
      Therefore, this enzyme is an attractive target for antimalarials. However,
      biochemical investigations of the parasite enzyme needed for the study of new
      drugs are challenging. In order to facilitate the study of new compounds
      targeting the enzyme, we are modifying the inhibitor binding sites of the yeast
      Saccharomyces cerevisiae to generate a complex that mimics the P. falciparum
      enzyme. In this study we focused on its Qo pocket, the site of atovaquone binding
      which is a leading antimalarial drug used in treatment and causal prophylaxis. We
      constructed and studied a series of mutants with modified Qo sites where yeast
      residues have been replaced by P. falciparum equivalents, or, for comparison, by
      human equivalents. Mitochondria were prepared from the yeast Plasmodium-like and
      human-like Qo mutants. We measured the bc 1 complex sensitivity to atovaquone,
      azoxystrobin, a Qo site targeting fungicide active against P. falciparum and
      RCQ06, a quinolone-derivative inhibitor of P. falciparum bc 1 complex.The data
      obtained highlighted variations in the Qo site that could explain the differences
      in inhibitor sensitivity between yeast, plasmodial and human enzymes. We showed
      that the yeast Plasmodium-like Qo mutants could be useful and easy-to-use tools
      for the study of that class of antimalarials. 

PMID- 23951231
TI  - Association between TCF7L2 gene polymorphism and cancer risk: a meta-analysis.
AB  - OBJECTIVE: The transcription factor 7-like 2 (TCF7L2) gene has been suggested to
      play an important role in the pathogenesis of cancer. However, the results have
      been inconsistent. In this study, we performed a meta-analysis to clarify the
      associations between TCF7L2 polymorphism and cancer risk. METHODS: Published
      literature from PubMed and EMBASE were retrieved. Pooled odds ratios (ORs) with
      95% confidence interval (CIs) were calculated using fixed- or random-effects
      model. RESULTS: A total of 19 studies (14,814 cases and 33,856 controls) were
      identified for the analysis of the association between TCF7L2 polymorphism and
      cancer risk. The results showed that TCF7L2 polymorphism was associated with
      breast cancer (Homogeneous model: OR=1.17, 95%CI=1.02-1.35, I (2) =21.8%, p for
      heterogeneity=0.276; Heterogeneous model: OR=1.11, 95%CI=1.03-1.20, I (2) =0.0%,
      p for heterogeneity=0.543), prostate cancer (Homogeneous model: OR=0.89,
      95%CI=0.84-0.96, I (2) =0.0%, p for heterogeneity=0.640; Heterogeneous model:
      OR=0.89, 95%CI=0.84-0.95, I (2) =0.0%, p for heterogeneity=0.871), and colon
      cancer (Heterogeneous model: OR=1.15, 95%CI=1.01-1.31, I (2) =0.0%, p for
      heterogeneity=0.658), but not with colorectal cancer, lung cancer, and ovarian
      cancer. CONCLUSIONS: The present meta-analysis indicated that there were
      significantly associations between the TCF7L2 rs7903146 polymorphism and risk of
      breast, prostate and colon cancers, rather than colorectal cancer, lung cancer,
      and ovarian cancer.

PMID- 23951232
TI  - Temporal-spatial dynamics in orthoptera in relation to nutrient availability and
      plant species richness.
AB  - Nutrient availability in ecosystems has increased dramatically over the last
      century. Excess reactive nitrogen deposition is known to negatively impact plant
      communities, e.g. by changing species composition, biomass and vegetation
      structure. In contrast, little is known on how such impacts propagate to higher
      trophic levels. To evaluate how nitrogen deposition affects plants and herbivore
      communities through time, we used extensive databases of spatially explicit
      historical records of Dutch plant species and Orthoptera (grasshoppers and
      crickets), a group of animals that are particularly susceptible to changes in the
      C:N ratio of their resources. We use robust methods that deal with the
      unstandardized nature of historical databases to test whether nitrogen deposition
      levels and plant richness changes influence the patterns of richness change of
      Orthoptera, taking into account Orthoptera species functional traits. Our
      findings show that effects indeed also propagate to higher trophic levels.
      Differences in functional traits affected the temporal-spatial dynamics of
      assemblages of Orthoptera. While nitrogen deposition affected plant diversity,
      contrary to our expectations, we could not find a strong significant effect of
      food related traits. However we found that species with low habitat specificity,
      limited dispersal capacity and egg deposition in the soil were more negativly
      affected by nitrogen deposition levels. Despite the lack of significant effect of
      plant richness or food related traits on Orthoptera, the negative effects of
      nitrogen detected within certain trait groups (e.g. groups with limited disperse
      ability) could be related to subtle changes in plant abundance and plant quality.
      Our results, however, suggest that the changes in soil conditions (where many
      Orthoptera species lay their eggs) or other habitat changes driven by nitrogen
      have a stronger influence than food related traits. To fully evaluate the
      negative effects of nitrogen deposition on higher trophic levels it is essential
      to take into account species life-history traits. 

PMID- 23951233
TI  - A sperm-plasma beta-N-acetyl-D-hexosaminidase interacting with a Chitinolytic
      beta-N-Acetyl-D-hexosaminidase in insect molting fluid.
AB  - Insects require molting fluids to shed the old cuticle during molting. beta-N
      acetyl-D-hexosaminidase, known as Hex1, together with various chitinases, is
      responsible for degrading the chitin component of the old cuticle. This study
      showed that another beta-N-acetyl-D-hexosaminidase, termed OfHex3, interacted
      with Hex1 and functioned in the molting fluid, although the homolog of OfHex3 was
      known as a sperm-plasma enzyme functioning in egg-sperm recognition. OfHex3 is an
      enzyme cloned from the insect Asian corn borer, Ostrinia furnacalis, which is one
      of the most destructive pests of maize. The enzymatic activity analysis indicated
      that OfHex3 was able to degrade chitooligosaccharides, but at a lower rate than
      that of OfHex1. Because OfHex3 did not have substrate inhibition, we deduced that
      the presence of OfHex3 might help OfHex1 relieve substrate inhibition during
      chitin degradation during molting. The expression patterns of OfHex3 during O.
      furnacalis development were studied by real-time PCR as well as western blot. The
      results showed that both gene transcription and protein translation levels of
      OfHex3 were up-regulated during larval-larval molting. The tissue-specific
      expression pattern analysis indicated that OfHex3 was mostly localized in the fat
      body and testis. All these data further supported that Hex3 was involved in
      molting as well as in fertilization. This study may help to understand the
      complexity of cuticle degradation during insect molting, and may provide a
      possible target for pest control. 

PMID- 23951234
TI  - Human hemorrhagic pulmonary leptospirosis: pathological findings and
      pathophysiological correlations.
AB  - BACKGROUND: Leptospirosis is a re-emerging zoonosis with protean clinical
      manifestations. Recently, the importance of pulmonary hemorrhage as a lethal
      complication of this disease has been recognized. In the present study, five
      human necropsies of leptospirosis (Weil's syndrome) with extensive pulmonary
      manifestations were analysed, and the antibodies expressed in blood vessels and
      cells involved in ion and water transport were used, seeking to better understand
      the pathophysiology of the lung injury associated with this disease. PRINCIPAL
      FINDINGS: Prominent vascular damage was present in the lung microcirculation,
      with decreased CD34 and preserved aquaporin 1 expression. At the periphery and
      even inside the extensive areas of edema and intraalveolar hemorrhage, enlarged,
      apparently hypertrophic type I pneumocytes (PI) were detected and interpreted as
      a non-specific attempt of clearence of the intraalveolar fluid, in which ionic
      transport, particularly of sodium, plays a predominant role, as suggested by the
      apparently increased ENaC and aquaporin 5 expression. Connexin 43 was present in
      most pneumocytes, and in the cytoplasm of the more preserved endothelial cells.
      The number of type II pneumocytes (PII) was slightly decreased when compared to
      normal lungs and those of patients with septicemia from other causes, a fact that
      may contribute to the progressively low PI count, resulting in deficient
      restoration after damage to the alveolar epithelial integrity and, consequently,
      a poor outcome of the pulmonary edema and hemorrhage. CONCLUSIONS: Pathogenesis
      of lung injury in human leptospirosis was discussed, and the possibility of
      primary non-inflammatory vascular damage was considered, so far of undefinite
      etiopathogenesis, as the initial pathological manifestation of the disease.

PMID- 23951235
TI  - Enhanced lipid oxidation and maintenance of muscle insulin sensitivity despite
      glucose intolerance in a diet-induced obesity mouse model.
AB  - BACKGROUND: Diet-induced obesity is a rising health concern which can lead to the
      development of glucose intolerance and muscle insulin resistance and, ultimately,
      type II diabetes mellitus. This research investigates the associations between
      glucose intolerance or muscle insulin resistance and tissue specific changes
      during the progression of diet-induced obesity. METHODOLOGY: C57BL/6J mice were
      fed a normal or high-fat diet (HFD; 60% kcal fat) for 3 or 8 weeks. Disease
      progression was monitored by measurements of body/tissue mass changes, glucose
      and insulin tolerance tests, and ex vivo glucose uptake in intact muscles. Lipid
      metabolism was analyzed using metabolic chambers and ex vivo palmitate assays in
      intact muscles. Skeletal muscle, liver and adipose tissues were analyzed for
      changes in inflammatory gene expression. Plasma was analyzed for insulin levels
      and inflammatory proteins. Histological techniques were used on muscle and liver
      cryosections to assess metabolic and morphological changes. PRINCIPAL
      FINDINGS/CONCLUSIONS: A rapid shift in whole body metabolism towards lipids was
      observed with HFD. Following 3 weeks of HFD, elevated total lipid oxidation and
      an oxidative fiber type shift had occurred in the skeletal muscle, which we
      propose was responsible for delaying intramyocellular lipid accumulation and
      maintaining muscle's insulin sensitivity. Glucose intolerance was present after
      three weeks of HFD and was associated with an enlarged adipose tissue depot,
      adipose tissue inflammation and excess hepatic lipids, but not hepatic
      inflammation. Furthermore, HFD did not significantly increase systemic or muscle
      inflammation after 3 or 8 weeks of HFD suggesting that early diet-induced obesity
      does not cause inflammation throughout the whole body. Overall these findings
      indicate skeletal muscle did not contribute to the development of HFD-induced
      impairments in whole-body glucose tolerance following 3 weeks of HFD.

PMID- 23951236
TI  - GSK3B and MAPT polymorphisms are associated with grey matter and intracranial
      volume in healthy individuals.
AB  - The microtubule-associated protein tau gene (MAPT) codes for a protein that plays
      an integral role in stabilisation of microtubules and axonal transport in
      neurons. As well as its role in susceptibility to neurodegeneration, previous
      studies have found an association between the MAPT haplotype and intracranial
      volume and regional grey matter volumes in healthy adults. The glycogen synthase
      kinase-3beta gene (GSK3B) codes for a serine/threonine kinase that phosphorylates
      various proteins, including tau, and has also been associated with risk for
      neurodegenerative disorders and schizophrenia. We examined the effects of MAPT
      and two functional promoter polymorphisms in GSK3B (rs3755557 and rs334558) on
      total grey matter and intracranial volume in three independent cohorts totaling
      776 neurologically healthy individuals. In vitro analyses revealed a significant
      effect of rs3755557 on gene expression, and altered binding of at least two
      transcription factors, Octamer transcription factor 1 (Oct-1) and Pre-B-cell
      leukemia transcription factor 1 (Pbx-1), to the GSK3B promoter. Meta-analysis
      across the three cohorts revealed a significant effect of rs3755557 on total grey
      matter volume (summary B = 0.082, 95% confidence interval = 0.037-0.128) and
      intracranial volume (summary B = 0.113, 95% confidence interval = 0.082-0.144).
      No significant effect was observed for MAPT H1/H2 diplotype or GSK3B rs334558 on
      total grey matter or intracranial volume. Our genetic and biochemical analyses
      have identified a role for GSK3B in brain development, which could have important
      aetiological implications for neurodegenerative and neurodevelopmental disorders.

PMID- 23951237
TI  - Chemical-functional diversity in cell-penetrating peptides.
AB  - Cell-penetrating peptides (CPPs) are a promising tool to overcome cell membrane
      barriers. They have already been successfully applied as carriers for several
      problematic cargoes, like e.g. plasmid DNA and (si)RNA, opening doors for new
      therapeutics. Although several hundreds of CPPs are already described in the
      literature, only a few commercial applications of CPPs are currently available.
      Cellular uptake studies of these peptides suffer from inconsistencies in used
      techniques and other experimental conditions, leading to uncertainties about
      their uptake mechanisms and structural properties. To clarify the structural
      characteristics influencing the cell-penetrating properties of peptides, the
      chemical-functional space of peptides, already investigated for cellular uptake,
      was explored. For 186 peptides, a new cell-penetrating (CP)-response was
      proposed, based upon the scattered quantitative results for cellular influx
      available in the literature. Principal component analysis (PCA) and a
      quantitative structure-property relationship study (QSPR), using chemo-molecular
      descriptors and our newly defined CP-response, learned that besides typical well
      known properties of CPPs, i.e. positive charge and amphipathicity, the shape,
      structure complexity and the 3D-pattern of constituting atoms influence the
      cellular uptake capacity of peptides. 

PMID- 23951238
TI  - Diverse gene cassettes in class 1 integrons of facultative oligotrophic bacteria
      of River Mahananda,West Bengal, India.
AB  - BACKGROUND: In this study a large random collection (n=2188) of facultative
      oligotrophic bacteria, from 90 water samples gathered in three consecutive years
      (2007-2009) from three different sampling sites of River Mahananda in Siliguri,
      West Bengal, India, were investigated for the presence of class 1 integrons and
      sequences of the amplification products. METHODOLOGY/PRINCIPAL FINDINGS: Replica
      plating method was employed for determining the antibiotic resistance profile of
      the randomly assorted facultative oligotrophic isolates. Genomic DNA from each
      isolate was analyzed by PCR for the presence of class 1 integron. Amplicons were
      cloned and sequenced. Numerical taxonomy and 16S rRNA gene sequence analyses were
      done to ascertain putative genera of the class 1 integron bearing isolates. Out
      of 2188 isolates, 1667 (76.19%) were antibiotic-resistant comprising of both
      single-antibiotic resistance (SAR) and multiple-antibiotic resistant (MAR), and
      521 (23.81%) were sensitive to all twelve different antibiotics used in this
      study. Ninety out of 2188 isolates produced amplicon(s) of varying sizes from
      0.15 to 3.45 KB. Chi-square (chi(2)) test revealed that the possession of class 1
      integron in sensitive, SAR and MAR is not equally probable at the 1% level of
      significance. Diverse antibiotic-resistance gene cassettes, aadA1, aadA2, aadA4,
      aadA5, dfrA1, dfrA5, dfrA7, dfrA12, dfrA16, dfrA17, dfrA28, dfrA30, dfr-IIe,
      blaIMP-9, aacA4, Ac-6'-Ib, oxa1, oxa10 and arr2 were detected in 64 isolates. The
      novel cassettes encoding proteins unrelated to any known antibiotic resistance
      gene function were identified in 26 isolates. Antibiotic-sensitive isolates have
      a greater propensity to carry gene cassettes unrelated to known antibiotic
      resistance genes. The integron-positive isolates under the class
      Betaproteobacteria comprised of only two genera, Comamonas and Acidovorax of
      family Comamonadaceae, while isolates under class Gammaproteobacteria fell under
      the families, Moraxellaceae, Pseudomonadaceae, Aeromonadaceae and
      Enterobacteriaceae. CONCLUSIONS: Oligotrophic bacteria are good sources of novel
      genes as well as potential reservoirs of antibiotic resistance gene casettes.

PMID- 23951239
TI  - Distinct gene expression signatures in lynch syndrome and familial colorectal
      cancer type x.
AB  - INTRODUCTION: Heredity is estimated to cause at least 20% of colorectal cancer.
      The hereditary nonpolyposis colorectal cancer subset is divided into Lynch
      syndrome and familial colorectal cancer type X (FCCTX) based on presence of
      mismatch repair (MMR) gene defects. PURPOSE: We addressed the gene expression
      signatures in colorectal cancer linked to Lynch syndrome and FCCTX with the aim
      to identify candidate genes and to map signaling pathways relevant in hereditary
      colorectal carcinogenesis. EXPERIMENTAL DESIGN: The 18 k whole-genome c-DNA
      mediated annealing, selection, extension, and ligation (WG-DASL) assay was
      applied to 123 colorectal cancers, including 39 Lynch syndrome tumors and 37
      FCCTX tumors. Target genes were technically validated using real-time
      quantitative RT-PCR (qRT-PCR) and the expression signature was validated in
      independent datasets. RESULTS: Colorectal cancers linked to Lynch syndrome and
      FCCTX showed distinct gene expression profiles, which by significance analysis of
      microarrays (SAM) differed by 2188 genes. Functional pathways involved were
      related to G-protein coupled receptor signaling, oxidative phosphorylation, and
      cell cycle function and mitosis. qRT-PCR verified altered expression of the
      selected genes NDUFA9, AXIN2, MYC, DNA2 and H2AFZ. Application of the 2188-gene
      signature to independent datasets showed strong correlation to MMR status.
      CONCLUSION: Distinct genetic profiles and deregulation of different canonical
      pathways apply to Lynch syndrome and FCCTX and key targets herein may be relevant
      to pursue for refined diagnostic and therapeutic strategies in hereditary
      colorectal cancer.

PMID- 23951240
TI  - Mangiferin prevents guinea pig tracheal contraction via activation of the nitric
      oxide-cyclic GMP pathway.
AB  - Previous studies have described the antispasmodic effect of mangiferin, a natural
      glucoside xanthone (2-C-beta-Dgluco-pyranosyl-1,3,6,7-tetrahydroxyxanthone) that
      is present in mango trees and other plants, but its mechanism of action remains
      unknown. The aim of this study was to examine the potential contribution of the
      nitric oxide-cyclic GMP pathway to the antispasmodic effect of mangiferin on
      isolated tracheal rings preparations. The functional effect of mangiferin on
      allergic and non-allergic contraction of guinea pig tracheal rings was assessed
      in conventional organ baths. Cultured tracheal rings were exposed to mangiferin
      or vehicle, and nitric oxide synthase (NOS) 3 and cyclic GMP (cGMP) levels were
      quantified using western blotting and enzyme immunoassays, respectively.
      Mangiferin (0.1-10 uM) inhibited tracheal contractions induced by distinct
      stimuli, such as allergen, histamine, 5-hydroxytryptamine or carbachol, in a
      concentration-dependent manner. Mangiferin also caused marked relaxation of
      tracheal rings that were precontracted by carbachol, suggesting that it has both
      anti-contraction and relaxant properties that are prevented by removing the
      epithelium. The effect of mangiferin was inhibited by the nitric oxide synthase
      inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME) (100 uM), and the
      soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one
      (ODQ) (10 uM), but not the adenylate cyclase inhibitor, 9-(tetrahydro-2
      furyl)adenine (SQ22536) (100 uM). The antispasmodic effect of mangiferin was also
      sensitive to K+ channel blockers, such as tetraethylammonium (TEA), glibenclamide
      and apamin. Furthermore, mangiferin inhibited Ca2+-induced contractions in K+ (60
      mM)-depolarised tracheal rings preparations. In addition, mangiferin increased
      NOS3 protein levels and cGMP intracellular levels in cultured tracheal rings.
      Finally, mangiferin-induced increase in cGMP levels was abrogated by co
      incubation with either ODQ or L-NAME. These data suggest that the antispasmodic
      effect of mangiferin is mediated by epithelium-nitric oxide- and cGMP-dependent
      mechanisms.

PMID- 23951241
TI  - Effect of HIV-1 subtypes on disease progression in rural Uganda: a prospective
      clinical cohort study.
AB  - OBJECTIVE: We examined the association of HIV-1 subtypes with disease progression
      based on three viral gene regions. DESIGN: A prospective HIV-1 clinical cohort
      study in rural Uganda. METHODS: Partial gag, env and pol genes were sequenced.
      Cox proportional hazard regression modelling was used to estimate adjusted hazard
      ratios (aHRs) of progression to: CD4<=250, AIDS onset and death, adjusted for
      sex, age and CD4 count at enrolment. RESULTS: Between 1990 and 2010, 292 incident
      cases were subtyped: 25% had subtype A, 45% had D, 26% had A/D recombinants, 1%
      had C and 4% were other recombinant forms. Of the 278 incident cases included in
      the disease progression analysis, 62% progressed to CD4<=250, 32% to AIDS, and
      34% died with a higher proportion being among subtype D cases. The proportions of
      individuals progressing to the three endpoints were significantly higher among
      individuals infected with subtype D. Throughout the study period, individuals
      infected with subtype D progressed faster to CD4<=250, adjusted HR (aHR), (95%
      CI) = 1.72 (1.16-2.54), but this was mainly due to events in the period before
      antiretroviral therapy (ART) introduction, when individuals infected with subtype
      D significantly progressed faster to CD4<=250 than subtype A cases; aHR (95% CI)
      = 1.78 (1.01-3.14). CONCLUSIONS: In this population, HIV-1 subtype D was the most
      prevalent and was associated with faster HIV-1 disease progression than subtype
      A. Further studies are needed to examine the effect of HIV-1 subtypes on disease
      progression in the ART period and their effect on the virological and
      immunological ART outcomes.

PMID- 23951242
TI  - Cofilin oligomer formation occurs in vivo and is regulated by cofilin
      phosphorylation.
AB  - BACKGROUND: ADF/cofilin proteins are key regulators of actin dynamics. Their
      function is inhibited by LIMK-mediated phosphorylation at Ser-3. Previous in
      vitro studies have shown that dependent on its concentration, cofilin either
      depolymerizes F-actin (at low cofilin concentrations) or promotes actin
      polymerization (at high cofilin concentrations). METHODOLOGY/PRINCIPAL FINDINGS:
      We found that after in vivo cross-linking with different probes, a cofilin
      oligomer (65 kDa) could be detected in platelets and endothelial cells. The
      cofilin oligomer did not contain actin. Notably, ADF that only depolymerizes F
      actin was present mainly in monomeric form. Furthermore, we found that formation
      of the cofilin oligomer is regulated by Ser-3 cofilin phosphorylation. Cofilin
      but not phosphorylated cofilin was present in the endogenous cofilin oligomer. In
      vitro, formation of cofilin oligomers was drastically reduced after
      phosphorylation by LIMK2. In endothelial cells, LIMK-mediated cofilin
      phosphorylation after thrombin-stimulation of EGFP- or DsRed2-tagged cofilin
      transfected cells reduced cofilin aggregate formation, whereas inhibition of
      cofilin phosphorylation after Rho-kinase inhibitor (Y27632) treatment of
      endothelial cells promoted formation of cofilin aggregates. In platelets, cofilin
      dephosphorylation after thrombin-stimulation and Y27632 treatment led to an
      increased formation of the cofilin oligomer. CONCLUSION/SIGNIFICANCE: Based on
      our results, we propose that an equilibrium exists between the monomeric and
      oligomeric forms of cofilin in intact cells that is regulated by cofilin
      phosphorylation. Cofilin phosphorylation at Ser-3 may induce conformational
      changes on the protein-protein interacting surface of the cofilin oligomer,
      thereby preventing and/or disrupting cofilin oligomer formation. Cofilin
      oligomerization might explain the dual action of cofilin on actin dynamics in
      vivo.

PMID- 23951243
TI  - Influence of parasite load on renal function in mice acutely infected with
      Trypanosoma cruzi.
AB  - BACKGROUND: Chagas disease is a neglected tropical disease caused by Trypanosoma
      cruzi. Despite the vast number of studies evaluating the pathophysiological
      mechanisms of the disease, the influence of parasite burden on kidney lesions
      remains unclear. Thus, the main goal of this work was to evaluate the effect of
      T. cruzi infection on renal function and determine whether there was a
      correlation between parasite load and renal injury using an acute experimental
      model of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Low, medium and high
      parasite loads were generated by infecting C57BL/6 mice with 300 (low), 3,000
      (medium) or 30,000 (high) numbers of "Y" strain trypomastigotes. We found that
      mice infected with T. cruzi trypomastigotes show increased renal injury. The
      infection resulted in reduced urinary excretion and creatinine clearance. We also
      observed a marked elevation in the ratio of urine volume to kidney and body
      weight, blood urea nitrogen, chloride ion, nitric oxide, pro- and anti
      inflammatory cytokines and the number of leukocytes in the blood and/or renal
      tissues of infected mice. Additionally, we observed the presence of the parasite
      in the cortical/medullary and peri-renal region, an increase of inflammatory
      infiltrate and of vascular permeability of the kidney. Overall, most renal
      changes occurred mainly in animals infected with high parasitic loads.
      CONCLUSIONS/SIGNIFICANCE: These data demonstrate that T. cruzi impairs kidney
      function, and this impairment is more evident in mice infected with high
      parasitic loads. Moreover, these data suggest that, in addition to the
      extensively studied cardiovascular effects, renal injury should be regarded as an
      important indicator for better understanding the pan-infectivity of the parasite
      and consequently for understanding the disease in experimental models.

PMID- 23951244
TI  - Metformin protects rat hepatocytes against bile acid-induced apoptosis.
AB  - BACKGROUND: Metformin is used in the treatment of Diabetes Mellitus type II and
      improves liver function in patients with non-alcoholic fatty liver disease
      (NAFLD). Metformin activates AMP-activated protein kinase (AMPK), the cellular
      energy sensor that is sensitive to changes in the AMP/ATP-ratio. AMPK is an
      inhibitor of mammalian target of rapamycin (mTOR). Both AMPK and mTOR are able to
      modulate cell death. AIM: To evaluate the effects of metformin on hepatocyte cell
      death. METHODS: Apoptotic cell death was induced in primary rat hepatocytes using
      either the bile acid glycochenodeoxycholic acid (GCDCA) or TNFalpha in
      combination with actinomycin D (actD). AMPK, mTOR and phosphoinositide-3 kinase
      (PI3K)/Akt were inhibited using pharmacological inhibitors. Apoptosis and
      necrosis were quantified by caspase activation, acridine orange staining and
      Sytox green staining respectively. RESULTS: Metformin dose-dependently reduces
      GCDCA-induced apoptosis, even when added 2 hours after GCDCA, without increasing
      necrotic cell death. Metformin does not protect against TNFalpha/ActD-induced
      apoptosis. The protective effect of metformin is dependent on an intact PI3
      kinase/Akt pathway, but does not require AMPK/mTOR-signaling. Metformin does not
      inhibit NF-kappaB activation. CONCLUSION: Metformin protects against bile acid
      induced apoptosis and could be considered in the treatment of chronic liver
      diseases accompanied by inflammation.

PMID- 23951245
TI  - Charting a moral life: the influence of stigma and filial duties on marital
      decisions among Chinese men who have sex with men.
AB  - INTRODUCTION: Stigma constitutes a critical challenge to the rising rates of HIV
      among Chinese men who have sex with men (MSM). It reduces willingness to disclose
      one's sexual orientation and can lead to concurrent sexual partnerships.
      Disclosure decisions are also affected by cultural norms that place pressures on
      sons to marry. In this manuscript, we characterize how stigma and cultural
      factors influenced Chinese MSM's decisions around disclosure and marriage. We
      seek to show that MSM's actions were motivated by moral considerations, even when
      those choices posed HIV transmission risks. METHODS: We conducted qualitative
      interviews with 30 MSM in Beijing, China. Interviews were audio-recorded,
      transcribed, and translated into English for analysis. Transcripts were coded
      using a procedure that allowed for themes to emerge organically. RESULTS:
      Participants struggled with feelings of shame and believed that others possessed
      stigmatizing attitudes about homosexuality. They had experienced relatively
      little discrimination because they infrequently disclosed their MSM status. In
      response to marital pressures, participant had to reconcile same-sex attractions
      with filial expectations. Their choices included: not being involved with women;
      putting on the appearance of a heterosexual relationship by marrying a lesbian;
      or fulfilling family expectations by marrying a heterosexual woman. Regardless of
      the decision, many rooted the justifications for their choices in the
      considerations they had given to others' needs. CONCLUSION: The growing epidemic
      among MSM in China requires action from the public health community. As programs
      are scaled up to serve these men, it is critical to remember that MSM, who often
      fear social sanction if they were to reveal their sexual orientation, continue to
      face the same pressures from culturally normative social duties as heterosexual
      men. Interventions must find ways to help men navigate a balance between their
      own needs and the responsibilities they feel toward their parents and others.

PMID- 23951246
TI  - The G-protein coupled estrogen receptor (GPER/GPR30) is a gonadotropin receptor
      dependent positive prognosticator in ovarian carcinoma patients.
AB  - Follicle stimulating hormone receptor (FSHR) and luteinizing hormone receptor
      (LHCGR) were demonstrated to impact upon survival of patients suffering from
      epithelial ovarian cancer (EOC). Though structure wise the G-protein coupled
      estrogen receptor (GPER/GPR30) is related to FSHR/LHCGR, its prognostic impact in
      EOC remains controversial. We recently found that FSHR negative patients
      represent a specific EOC subgroup that may behave differently in respect to both
      treatment response and prognosis. Hence, the current study aimed to analyze how
      GPER may interact with the FSHR/LHCGR system in EOC and whether the prognostic
      significance of GPER in EOC cases (n=151) may be dependent on the FSHR/LHCGR
      immunophenotype of the tumor. Ovarian cancer cell lines were used to study how
      FSH and LH regulate GPER and whether GPER activation differentially affects in
      vitro cell proliferation in presence/absence of activated FSHR/LHCGR. In EOC
      tissue, GPER correlated with FSHR/LHCGR and was related to prolonged overall
      survival only in FSHR/LHCGR negative patients. Although GPER was found to be
      specifically induced by LH/FSH, GPER agonists (4-Hydroxy-Tamoxifen, G1) reduced
      EOC cell proliferation only in case of LH/FSH unstimulated pathways. To the same
      direction, only patients characterized as LHCGR/FSHR negative seem to gain from
      GPER in terms of survival. Our combined tissue and in vitro results support thus
      the hypothesis that GPER activation could be of therapeutic benefit in LHCGR/FSHR
      negative EOC patients. Further studies are needed to evaluate the impact of GPER
      activation on a clinical scheme.

PMID- 23951247
TI  - Reduced risk for metabolic syndrome and insulin resistance associated with ovo
      lacto-vegetarian behavior in female Buddhists: a case-control study.
AB  - INTRODUCTION: The association of vegetarian status with the risk of metabolic
      syndrome (MetS) is not clear. In Asia, Buddhists often have vegetarian behavior
      for religious rather than for health reasons. We hypothesize that the vegetarian
      in Buddhism is associated with better metabolic profiles, lower risk for the MetS
      and insulin resistance (IR). METHODS: We enrolled 391 female vegetarians (~80%
      lacto-ovo-vegetarians) and 315 non-vegetarians from health-checkup clinics at a
      Buddhist hospital in Taiwan. RESULTS: The vegetarian status was associated with
      lower body mass index, smaller waist circumference, lower total cholesterol,
      lower low density lipoprotein-cholesterol (LDL-C), and lower HDL-C in
      multivariate linear regression analyses. Despite having lower HDL-C level, the
      vegetarians had significantly lower total cholesterol/HDL-C and LDL-C/HDL-C
      ratios. After adjusting the other covariates, the risks for the MetS were lower
      for ovo-lacto-vegetarians of 1-11 years and >11 years respectively by 54% (odds
      ratio [OR] =0.46, 95%C.I.:0.26-0.79) and 57% (OR=0.43, 95%C.I.:0.23-0.76)
      compared to non-vegetarians by the IDF criteria. Likewise, they were lower
      respectively by 45% (OR=0.55, 95%C.I.:0.32-0.92) and 42% (OR=0.58, 95%C.I.:0.33
      0.997), for the MetS by the modified NCEP criteria. In the subgroup of non
      diabetic subjects, the vegetarians also had lower risk for IR by HOMA compared to
      the non-vegetarians (OR=0.71, 95%C.I.:0.48-1.06). CONCLUSION: The vegetarian
      behavior, mainly lacto-ovo-vegetarian, related to Buddhism, although not meant
      for its health effects, is associated with reduced risk for the MetS and IR and
      may potentially provide metabolic and cardiovascular protective effects in women.

PMID- 23951248
TI  - Mesenchymal stem cell conditioning promotes rat oligodendroglial cell maturation.
AB  - Oligodendroglial progenitor/precursor cells (OPCs) represent the main cellular
      source for the generation of new myelinating oligodendrocytes in the adult
      central nervous system (CNS). In demyelinating diseases such as multiple
      sclerosis (MS) myelin repair activities based on recruitment, activation and
      differentiation of resident OPCs can be observed. However, the overall degree of
      successful remyelination is limited and the existence of an MS-derived anti
      oligodendrogenic milieu prevents OPCs from contributing to myelin repair. It is
      therefore of considerable interest to understand oligodendroglial homeostasis and
      maturation processes in order to enable the development of remyelination
      therapies. Mesenchymal stem cells (MSC) have been shown to exert positive
      immunomodulatory effects, reduce demyelination, increase neuroprotection and to
      promote adult neural stem cell differentiation towards the oligodendroglial
      lineage. We here addressed whether MSC secreted factors can boost the OPC's
      oligodendrogenic capacity in a myelin non-permissive environment. To this end, we
      analyzed cellular morphologies, expression and regulation of key factors involved
      in oligodendroglial fate and maturation of primary rat cells upon incubation with
      MSC-conditioned medium. This demonstrated that MSC-derived soluble factors
      promote and accelerate oligodendroglial differentiation, even under astrocytic
      endorsing conditions. Accelerated maturation resulted in elevated levels of
      myelin expression, reduced glial fibrillary acidic protein expression and was
      accompanied by downregulation of prominent inhibitory differentiation factors
      such as Id2 and Id4. We thus conclude that apart from their suggested application
      as potential anti-inflammatory and immunomodulatory MS treatment, these cells
      might also be exploited to support endogenous myelin repair activities. 

PMID- 23951249
TI  - Differential impact of statin on new-onset diabetes in different age groups: a
      population-based case-control study in women from an asian country.
AB  - BACKGROUND: Statins reduce cardiovascular risks but increase the risk of new
      onset diabetes (NOD). The aim of this study is to determine what effect, if any,
      statins have on the risk of NOD events in a population-based case-control study.
      An evaluation of the relationship between age and statin-exposure on NOD risks
      was further examined in a female Asian population. METHOD: In a nationwide case
      controlled study, the authors assessed 1065 female NOD patients and 10650
      controls with matching ages, genders and physician visit dates. The impact of
      statin-exposure on NOD was examined through multiple logistic regression models.
      Subgroup analysis for exploring the risk of NOD and statin-exposure in different
      age groups was performed. RESULTS: Statin-exposure was statistically
      significantly associated with increased new-onset diabetes risks using
      multivariate analysis. Interaction effect between age and statin-exposure on NOD
      risk was noted. For atorvastatin, the risk of cDDDs>60 was highest among the 55
      64 year-olds (adjusted odds ratio [OR], 8.0; 95% confidence interval [CI], 2.57
      24.90). For rosuvastatin, the risk of cDDDs>60 was highest among the 40-54 year
      olds (adjusted OR, 14.8; 95% CI, 2.27-96.15). For simvastatin, the risk of
      cDDDs>60 was highest among the 55-64 year-olds (adjusted OR, 15.8; 95% CI, 5.77
      43.26). For pravastatin, the risk of cDDDs>60 was highest among the 55-64 year
      olds (adjusted OR, 14.0; 95% CI, 1.56-125.18). CONCLUSIONS: This population-based
      study found that statin use is associated with an increased risk of NOD in women.
      The risk of statin-related NOD was more evident for women aged 40-64 years
      compared to women aged 65 or more, and was cumulative-dose dependent. The use of
      statins should always be determined by weighing the clinical benefits and
      potential risks for NOD, and the patients should be continuously monitored for
      adverse effects.

PMID- 23951250
TI  - Sequencing mRNA from cryo-sliced Drosophila embryos to determine genome-wide
      spatial patterns of gene expression.
AB  - Complex spatial and temporal patterns of gene expression underlie embryo
      differentiation, yet methods do not yet exist for the efficient genome-wide
      determination of spatial expression patterns during development. In situ imaging
      of transcripts and proteins is the gold-standard, but it is difficult and time
      consuming to apply to an entire genome, even when highly automated. Sequencing,
      in contrast, is fast and genome-wide, but is generally applied to homogenized
      tissues, thereby discarding spatial information. To take advantage of the
      efficiency and comprehensiveness of sequencing while retaining spatial
      information, we cryosectioned individual blastoderm stage Drosophila melanogaster
      embryos along the anterior-posterior axis and developed methods to reliably
      sequence the mRNA isolated from each 25 um slice. The spatial patterns of gene
      expression we infer closely match patterns previously determined by in situ
      hybridization and microscopy. We applied this method to generate a genome-wide
      timecourse of spatial gene expression from shortly after fertilization through
      gastrulation. We identified numerous genes with spatial patterns that have not
      yet been described in the several ongoing systematic in situ based projects. This
      simple experiment demonstrates the potential for combining careful anatomical
      dissection with high-throughput sequencing to obtain spatially resolved gene
      expression on a genome-wide scale. 

PMID- 23951251
TI  - Salivary gland hypofunction in tyrosylprotein sulfotransferase-2 knockout mice is
      due to primary hypothyroidism.
AB  - BACKGROUND: Protein-tyrosine sulfation is a post-translational modification of an
      unknown number of secreted and membrane proteins mediated by two known Golgi
      tyrosylprotein sulfotransferases (TPST-1 and TPST-2). We reported that Tpst2-/-
      mice have mild-moderate primary hypothyroidism, whereas Tpst1-/- mice are
      euthyroid. While using magnetic resonance imaging (MRI) to look at the thyroid
      gland we noticed that the salivary glands in Tpst2-/- mice appeared smaller than
      in wild type mice. This prompted a detailed analysis to compare salivary gland
      structure and function in wild type, Tpst1-/-, and Tpst2 -/- mice.
      METHODOLOGY/PRINCIPAL FINDINGS: Quantitative MRI imaging documented that salivary
      glands in Tpst2-/- females were (~) 30% smaller than wild type or Tpst1-/- mice
      and that the granular convoluted tubules in Tpst2-/- submandibular glands were
      less prominent and were almost completely devoid of exocrine secretory granules
      compared to glands from wild type or Tpst1-/- mice. In addition, pilocarpine
      induced salivary flow and salivary alpha-amylase activity in Tpst2-/- mice of
      both sexes was substantially lower than in wild type and Tpst1-/- mice. Anti
      sulfotyrosine Western blots of salivary gland extracts and saliva showed no
      differences between wild type, Tpst1-/-, and Tpst2-/- mice, suggesting that the
      salivary gland hypofunction is due to factor(s) extrinsic to the salivary glands.
      Finally, we found that all indicators of hypothyroidism (serum T4, body weight)
      and salivary gland hypofunction (salivary flow, salivary alpha-amylase activity,
      histological changes) were restored to normal or near normal by thyroid hormone
      supplementation. CONCLUSIONS/SIGNIFICANCE: Our findings conclusively demonstrate
      that low body weight and salivary gland hypofunction in Tpst2-/- mice is due
      solely to primary hypothyroidism.

PMID- 23951252
TI  - A novel approach to quantify time series differences of gait data using attractor
      attributes.
AB  - In this paper we introduce a new method to expressly use live/corporeal data in
      quantifying differences of time series data with an underlying limit cycle
      attractor; and apply it using an example of gait data. Our intention is to
      identify gait pattern differences between diverse situations and classify them on
      group and individual subject levels. First we approximated the limit cycle
      attractors, from which three measures were calculated: deltaM amounts to the
      difference between two attractors (a measure for the differences of two
      movements), deltaD computes the difference between the two associated deviations
      of the state vector away from the attractor (a measure for the change in movement
      variation), and deltaF, a combination of the previous two, is an index of the
      change. As an application we quantified these measures for walking on a treadmill
      under three different conditions: normal walking, dual task walking, and walking
      with additional weights at the ankle. The new method was able to successfully
      differentiate between the three walking conditions. Day to day repeatability,
      studied with repeated trials approximately one week apart, indicated excellent
      reliability for deltaM (ICC(ave) > 0.73 with no differences across days; p >
      0.05) and good reliability for deltaD (ICC(ave) = 0.414 to 0.610 with no
      differences across days; p > 0.05). Based on the ability to detect differences in
      varying gait conditions and the good repeatability of the measures across days,
      the new method is recommended as an alternative to expensive and time consuming
      techniques of gait classification assessment. In particular, the new method is an
      easy to use diagnostic tool to quantify clinical changes in neurological
      patients.

PMID- 23951253
TI  - A naturalistic study of the acceptability and effectiveness of internet-delivered
      cognitive behavioural therapy for psychiatric disorders in older australians.
AB  - OBJECTIVES: The current study investigates the acceptability, effectiveness and
      uptake of internet-delivered cognitive behavioural therapy (iCBT) amongst older
      individuals (>60 years) seeking psychiatric treatment in general practice.
      METHODS: The sample consisted of 2413 (mean age 39.5; range 18-83 years) patients
      prescribed iCBT through This Way Up clinic by their primary care clinician. The
      intervention consisted of six fully automated, unassisted online lessons specific
      to four disorders major depression, generalised anxiety disorder, panic disorder
      or social phobia. Patients were categorised into five age groups (18-29 years, 30
      39 years, 40-49 years, 50-59 years, 60 years and above). 225 (9.3%) patients were
      aged over 60 years. Analyses were conducted across the four disorders to ensure
      sufficient sample sizes in the 60 years and older age group. Age differences in
      adherence to the six lesson courses were assessed to demonstrate acceptability.
      Age-based reductions in psychological distress (Kessler Psychological Distress
      Scale; K10) and disability (the World Health Organisation Disability Assessment
      Schedule; WHODAS-II) were compared to demonstrate effectiveness. To evaluate the
      uptake of iCBT, the age distribution of those commencing iCBT was compared with
      the prevalence of these disorders in the 2007 Australian National Survey of
      Mental Health and Well-Being. RESULTS: Older adults were more likely to complete
      all six lessons when compared with their younger counterparts. Marginal model
      analyses indicated that there were significant reductions in the K10 and WHODAS
      II from baseline to post-intervention, regardless of age (p<0.001). The
      measurement occasion by age interactions were not significant, indicating that
      individuals showed similar reductions in the K10 and WHODAS-II regardless of age.
      In general, the age distribution of individuals commencing the iCBT courses
      matched the age distribution of the four diagnoses in the Australian general
      population, indicating that iCBT successfully captures older individuals who need
      treatment. CONCLUSION: iCBT is effective and acceptable for use in older
      populations.

PMID- 23951254
TI  - Transcript profiling identifies iqgap2(-/-) mouse as a model for advanced human
      hepatocellular carcinoma.
AB  - It is broadly accepted that genetically engineered animal models do not always
      recapitulate human pathobiology. Therefore identifying best-fit mouse models of
      human cancers that truly reflect the corresponding human disease is of vital
      importance in elucidating molecular mechanisms of tumorigenesis and developing
      preventive and therapeutic approaches. A new hepatocellular carcinoma (HCC) mouse
      model lacking a novel putative tumor suppressor IQGAP2 has been generated by our
      laboratory. The aim of this study was to obtain the molecular signature of
      Iqgap2(-/-) HCC tumors and establish the relevance of this model to human
      disease. Here we report a comprehensive transcriptome analysis of Iqgap2(-/-)
      livers and a cross-species comparison of human and Iqgap2(-/-) HCC tumors using
      Significance Analysis of Microarray (SAM) and unsupervised hierarchical
      clustering analysis. We identified the Wnt/beta-catenin signaling pathway as the
      top canonical pathway dysregulated in Iqgap2(-/-) livers. We also demonstrated
      that Iqgap2(-/-) hepatic tumors shared genetic signatures with HCC tumors from
      patients with advanced disease as evidenced by a 78% mouse-to-human microarray
      data set concordance rate with 117 out of 151 identified ortholog genes having
      similar expression profiles across the two species. Collectively, these results
      indicate that the Iqgap2 knockout mouse model closely recapitulates human HCC at
      the molecular level and supports its further application for the study of this
      disease. 

PMID- 23951255
TI  - Long-term monitoring of microsporidia, Cryptosporidium and Giardia infections in
      western Lowland Gorillas (Gorilla gorilla gorilla) at different stages of
      habituation in Dzanga Sangha Protected Areas, Central African Republic.
AB  - BACKGROUND: Infectious diseases pose one of the greatest threats to endangered
      species, and a risk of gastrointestinal parasite transmission from humans to
      wildlife has always been considered as a major concern of tourism. Increased
      anthropogenic impact on primate populations may result in general changes in
      communities of their parasites, and also in a direct exchange of parasites
      between humans and primates. AIMS: To evaluate the impact of close contact with
      humans on the occurrence of potentially zoonotic protists in great apes, we
      conducted a long-term monitoring of microsporidia, Cryptosporidium and Giardia
      infections in western lowland gorillas at different stages of the habituation
      process, humans, and other wildlife in Dzanga-Sangha Protected Areas in the
      Central African Republic. RESULTS: We detected Encephalitozoon cuniculi genotypes
      I and II (7.5%), Enterocytozoon bieneusi genotype D and three novel genotypes
      (gorilla 1-3) (4.0%), Giardia intestinalis subgroup A II (2.0%) and
      Cryptosporidium bovis (0.5%) in gorillas, whereas in humans we found only G.
      intestinalis subgroup A II (2.1%). In other wild and domestic animals we recorded
      E. cuniculi genotypes I and II (2.1%), G. intestinalis assemblage E (0.5%) and C.
      muris TS03 (0.5%). CONCLUSION: Due to the non-specificity of E. cuniculi
      genotypes we conclude that detection of the exact source of E. cuniculi infection
      is problematic. As Giardia intestinalis was recorded primarily in gorilla groups
      with closer human contact, we suggest that human-gorilla transmission has
      occurred. We call attention to a potentially negative impact of habituation on
      selected pathogens which might occur as a result of the more frequent presence of
      humans in the vicinity of both gorillas under habituation and habituated
      gorillas, rather than as a consequence of the close contact with humans, which
      might be a more traditional assumption. We encourage to observe the sections
      concerning hygiene from the IUCN best practice guidelines for all sites where
      increased human-gorilla contact occurs.

PMID- 23951256
TI  - Optimisation of recombinant production of active human cardiac SERCA2a ATPase.
AB  - Methods for recombinant production of eukaryotic membrane proteins, yielding
      sufficient quantity and quality of protein for structural biology, remain a
      challenge. We describe here, expression and purification optimisation of the
      human SERCA2a cardiac isoform of Ca(2+) translocating ATPase, using Saccharomyces
      cerevisiae as the heterologous expression system of choice. Two different
      expression vectors were utilised, allowing expression of C-terminal fusion
      proteins with a biotinylation domain or a GFP- His8 tag. Solubilised membrane
      fractions containing the protein of interest were purified onto Streptavidin
      Sepharose, Ni-NTA or Talon resin, depending on the fusion tag present.
      Biotinylated protein was detected using specific antibody directed against SERCA2
      and, advantageously, GFP-His8 fusion protein was easily traced during the
      purification steps using in-gel fluorescence. Importantly, talon resin affinity
      purification proved more specific than Ni-NTA resin for the GFP-His8 tagged
      protein, providing better separation of oligomers present, during size exclusion
      chromatography. The optimised method for expression and purification of human
      cardiac SERCA2a reported herein, yields purified protein (> 90%) that displays a
      calcium-dependent thapsigargin-sensitive activity and is suitable for further
      biophysical, structural and physiological studies. This work provides support for
      the use of Saccharomyces cerevisiae as a suitable expression system for
      recombinant production of multi-domain eukaryotic membrane proteins. 

PMID- 23951257
TI  - Habitat quality affects early physiology and subsequent neuromotor development of
      juvenile black-capped chickadees.
AB  - In songbirds, the ability to learn and render the species-specific song is
      influenced by the development of both the song nuclei in the brain and the syrinx
      (bird's vocal apparatus) early in the bird's life. In black-capped chickadees
      (Poecille atricapillus), habitat quality is known to affect song structure, with
      birds in high-quality habitat (mature forest) having a higher song consistency
      than birds in low-quality habitat (young forest). Although this difference is
      suspected to stem from differences in development, the developmental status of
      juvenile birds in either habitat remains unexplored. In this study, we used
      ptilochronology and feather corticosterone to compare the conditional state of
      juvenile chickadees in young and mature forest during two distinct periods of
      song learning - the sensory phase, which occurs prior to settlement, and the
      sensorimotor phase, which occurs post-settlement. A sample of juvenile males was
      captured and euthanized several weeks prior to their first breeding season to
      compare the development of song center nuclei and syrinx in both habitats. The
      corticosterone levels of natally-grown feathers were greater among birds that
      settled in mature than young forests - as these feathers were grown pre
      settlement, they reflect differences in physiology during the sensory phase. This
      difference in conditional state is reflected by differences in syrinx and song
      center nuclei development later during the sensorimotor phase - birds in young
      forest have smaller syrinx, and moderately-larger RA, than birds in mature
      forest. Those differences could be responsible for the difference in consistency
      in song structure observed across habitats. The difference in physiological state
      across habitats, combined with potential compounding effect of differences in
      winter resources between habitats, could influence the difference in syrinx and
      neural development seen in juvenile males during the early spring, and influence
      the male's ability to learn and render their species-specific song. 

PMID- 23951258
TI  - The economic burden of cancers on Indian households.
AB  - We assessed the burden of cancer on households' out-of-pocket health spending,
      non-medical consumption, workforce participation, and debt and asset sales using
      data from a nationally representative health and morbidity survey in India for
      2004 of nearly 74 thousand households. Propensity scores were used to match
      households containing a member diagnosed with cancer (i.e. cancer-affected
      households) to households with similar socioeconomic and demographic
      characteristics (controls). Our estimates are based on data from 1,645 households
      chosen through matching. Cancer-affected households experienced higher levels of
      outpatient visits and hospital admissions and increased out-of-pocket health
      expenditures per member, relative to controls. Cancer-affected households spent
      between Indian Rupees (INR) 66 and INR 85 more per member on healthcare over a 15
      day reference period, than controls and additional expenditures (per member)
      incurred on inpatient care by cancer-affected households annually is equivalent
      to 36% to 44% of annual household expenditures of matched controls. Members
      without cancer in cancer-affected households used less health-care and spent less
      on healthcare. Overall, adult workforce participation rates were lower by between
      2.4 and 3.2 percentage points compared to controls; whereas workforce
      participation rates among adult members without cancer were higher than in
      control households. Cancer-affected households also had significantly higher
      rates of borrowing and asset sales for financing outpatient care that were 3.3%
      to 4.0% higher compared to control households; and even higher for inpatient
      care. 

PMID- 23951259
TI  - A primate specific extra domain in the molecular chaperone Hsp90.
AB  - Hsp90 (heat shock protein 90) is an essential molecular chaperone that mediates
      folding and quality control of client proteins. Many of them such as protein
      kinases, steroid receptors and transcription factors are involved in cellular
      signaling processes. Hsp90 undergoes an ATP hydrolysis dependent conformational
      cycle to assist folding of the client protein. The canonical Hsp90 shows a
      typical composition of three distinct domains and interacts with individual
      cochaperone partners such as Hop, Cdc37 and Aha1 (activator of Hsp90 ATPase) that
      regulate the reaction cycle of the molecular chaperone. A bioinformatic survey
      identified an additional domain of 122 amino acids in front of the canonical
      Hsp90 sequence. This extra domain (E domain) is specific to the Catarrhini or
      drooping nose monkeys, a subdivision of the higher primates that includes man,
      the great apes and the old world monkeys but is absent from all other species.
      Our biochemical analysis reveals that Hsp103 associates with cochaperone proteins
      such as Hop, Cdc37 and Aha1 similar to Hsp90. However, the extra domain reduces
      the ATP hydrolysis rate to about half when compared to Hsp90 thereby acting as a
      negative regulator of the molecular chaperones intrinsic ATPase activity. 

PMID- 23951260
TI  - The tick-derived anticoagulant madanin is processed by thrombin and factor Xa.
AB  - The cysteine-less peptidic anticoagulants madanin-1 and madanin-2 from the bush
      tick Haemaphysalis longicornis are the founding members of the MEROPS inhibitor
      family I53. It has been previously suggested that madanins exert their functional
      activity by competing with physiological substrates for binding to the positively
      charged exosite I (fibrinogen-binding exosite) of alpha-thrombin. We hereby
      demonstrate that competitive inhibition of alpha-thrombin by madanin-1 or madanin
      2 involves binding to the enzyme's active site. Moreover, the blood coagulation
      factors IIa and Xa are shown to hydrolyze both inhibitors at different, although
      partially overlapping cleavage sites. Finally, the three-dimensional structure of
      the complex formed between human alpha-thrombin and a proteolytic fragment of
      madanin-1, determined by X-ray crystallography, elucidates the molecular details
      of madanin-1 recognition and processing by the proteinase. Taken together, the
      current findings establish the mechanism of action of madanins, natural
      anticoagulants that behave as cleavable competitive inhibitors of thrombin. 

PMID- 23951261
TI  - Diabetes-induced superoxide anion and breakdown of the blood-retinal barrier:
      role of the VEGF/uPAR pathway.
AB  - Diabetes-induced breakdown of the blood-retinal barrier (BRB) has been linked to
      hyperglycemia-induced expression of vascular endothelial growth factor (VEGF) and
      is likely mediated by an increase in oxidative stress. We have shown that VEGF
      increases permeability of retinal endothelial cells (REC) by inducing expression
      of urokinase plasminogen activator receptor (uPAR). The purpose of this study was
      to define the role of superoxide anion in VEGF/uPAR expression and BRB breakdown
      in diabetes. Studies were performed in streptozotocin diabetic rats and mice and
      high glucose (HG) treated REC. The superoxide dismutase (SOD) mimetic tempol
      blocked diabetes-induced permeability and uPAR expression in rats and the cell
      permeable SOD inhibited HG-induced expression of uPAR and VEGF in REC. Inhibiting
      VEGFR blocked HG-induced expression of VEGF and uPAR and GSK-3beta
      phosphorylation in REC. HG caused beta-catenin translocation from the plasma
      membrane into the cytosol and nucleus. Treatment with HG-conditioned media
      increased REC paracellular permeability that was blocked by anti-uPA or anti-uPAR
      antibodies. Moreover, deletion of uPAR blocked diabetes-induced BRB breakdown and
      activation of MMP-9 in mice. Together, these data indicate that diabetes-induced
      oxidative stress triggers BRB breakdown by a mechanism involving uPAR expression
      through VEGF-induced activation of the GSK3beta/beta-catenin signaling pathway. 

PMID- 23951262
TI  - Comparison of ablation zones among different tissues using 2450-MHz cooled-shaft
      microwave antenna: results in ex vivo porcine models.
AB  - BACKGROUND: For complete tumor ablation in different tissues, it is necessary to
      investigate the exact coagulation zone of microwave ablation in different
      tissues. The aim of this study was to compare the extent of microwave ablation
      zone in muscle, liver and adipose tissue in ex vivo porcine models and assess the
      shape of microwave coagulation zone among these tissues. MATERIALS AND METHODS:
      Microwave ablations were performed in ex vivo porcine muscle, liver and adipose
      tissue using 2450-MHz cooled-shaft microwave antenna. The content of water, fat
      and protein in these three tissues was determined. Two power increments (40 and
      80 W) and five time increments (1, 3, 5, 7, and 10 minutes) were used in this
      study. Diameters and shapes of the ablation zones were assessed on gross
      specimens. RESULTS: The average percentages of water, fat and protein in these
      three tissues were significantly different (P < 0.001), respectively. The long
      axis and short-axis diameters among these three tissues at each time-power
      combination were not significantly different (P > 0.05). The coagulation zones
      were all elliptical in muscle, liver and adipose tissue. When microwave ablation
      was performed in the tissue containing both muscle and adipose tissue, the
      coagulation zone was also elliptical. Regardless of the output power, the
      ellipticity index (EI) value of 1 minute treatment duration was higher than that
      of 10 minutes treatment duration (P < 0.05). Furthermore, the EI value did not
      decrease significantly when the treatment duration was more than 5 minutes (P >
      0.05). CONCLUSION: The extent of microwave ablation zones was not significantly
      different among completely different tissues. Microwave ablations with >= 5
      minutes time duration can induce coagulation zones with clinical desirable shape.
      Future clinical studies are still required to determine the role of microwave
      ablation in different tissues.

PMID- 23951263
TI  - Gag-positive reservoir cells are susceptible to HIV-specific cytotoxic T
      lymphocyte mediated clearance in vitro and can be detected in vivo [corrected].
AB  - Resting CD4+T cells infected with HIV persist in the presence of suppressive anti
      viral therapy (ART) and are barriers to a cure. One potential curative approach,
      therapeutic vaccination, is fueled by recognition of the ability of a subset of
      elite controllers (EC) to control virus without therapy due to robust anti-HIV
      immune responses. Controllers have low levels of integrated HIV DNA and low
      levels of replication competent virus, suggesting a small reservoir. As our
      recent data indicates some reservoir cells can produce HIV proteins (termed GPR
      cells for Gag-positive reservoir cells), we hypothesized that a fraction of HIV
      expressing resting CD4+T cells could be efficiently targeted and cleared in
      individuals who control HIV via anti-HIV cytotoxic T lymphocytes (CTL). To test
      this we examined if superinfected resting CD4+T cells from EC express HIV Gag
      without producing infectious virus and the susceptibility of these cells to CTL.
      We found that resting CD4+T cells expressed HIV Gag and were cleared by
      autologous CD8+T cells from EC. Importantly, we found the extent of CTL clearance
      in our in vitro assay correlates with in vivo reservoir size and that a
      population of Gag expressing resting CD4+T cells exists in vivo in patients well
      controlled on therapy. 

PMID- 23951264
TI  - Scales and tooth whorls of ancient fishes challenge distinction between external
      and oral 'teeth'.
AB  - The debate about the origin of the vertebrate dentition has been given fresh fuel
      by new fossil discoveries and developmental studies of extant animals. Odontodes
      (teeth or tooth-like structures) can be found in two distinct regions, the
      'internal' oropharyngeal cavity and the 'external' skin. A recent hypothesis
      argues that regularly patterned odontodes is a specific oropharyngeal feature,
      whereas odontodes in the external skeleton lack this organization. However, this
      argument relies on the skeletal system of modern chondrichthyans (sharks and
      their relatives), which differ from other gnathostome (jawed vertebrate) groups
      in not having dermal bones associated with the odontodes. Their external skeleton
      is also composed of monoodontode 'placoid scales', whereas the scales of most
      early fossil gnathostomes are polyodontode, i.e. constructed from several
      odontodes on a shared bony base. Propagation phase contrast X-ray Synchrotron
      microtomography (PPC-SRuCT) is used to study the polyodontode scales of the early
      bony fish Andreolepis hedei. The odontodes constructing a single scale are
      reconstructed in 3D, and a linear and regular growth mechanism similar to that in
      a gnathostome dentition is confirmed, together with a second, gap-filling growth
      mechanism. Acanthodian tooth whorls are described, which show that ossification
      of the whorl base preceded and probably patterned the development of the dental
      lamina, in contrast to the condition in sharks where the dental lamina develops
      early and patterns the dentition.The new findings reveal, for the first time, how
      polyodontode scales grow in 3D in an extinct bony fish. They show that dentition
      like odontode patterning occurs on scales and that the primary patterning unit of
      a tooth whorl may be the bony base rather than the odontodes it carries. These
      results contradict the hypothesis that oropharyngeal and external odontode
      skeletons are fundamentally separate and suggest that the importance of dermal
      bone interactions to odontode patterning has been underestimated. 

PMID- 23951265
TI  - Childhood maltreatment is associated with larger left thalamic gray matter volume
      in adolescents with generalized anxiety disorder.
AB  - BACKGROUND: Generalized anxiety disorder (GAD) is a common anxiety disorder that
      usually begins in adolescence. Childhood maltreatment is highly prevalent and
      increases the possibility for developing a variety of mental disorders including
      anxiety disorders. An earlier age at onset of GAD is significantly related to
      maltreatment in childhood. Exploring the underpinnings of the relationship
      between childhood maltreatment and adolescent onset GAD would be helpful in
      identifying the potential risk markers of this condition. METHODS: Twenty-six
      adolescents with GAD and 25 healthy controls participated in this study. A
      childhood trauma questionnaire (CTQ) was introduced to assess childhood
      maltreatment. All subjects underwent high-resolution structural magnetic
      resonance scans. Voxel-based morphometry (VBM) was used to investigate gray
      matter alterations. RESULTS: Significantly larger gray matter volumes of the
      right putamen were observed in GAD patients compared to healthy controls. In
      addition, a significant diagnosis-by-maltreatment interaction effect for the left
      thalamic gray matter volume was revealed, as shown by larger volumes of the left
      thalamic gray matter in GAD patients with childhood maltreatment compared with
      GAD patients without childhood maltreatment as well as with healthy controls
      with/without childhood maltreatment. A significant positive association between
      childhood maltreatment and left thalamic gray matter volume was only seen in GAD
      patients. CONCLUSIONS: These findings revealed an increased volume in the
      subcortical regions in adolescent GAD, and the alterations in the left thalamus
      might be involved in the association between childhood maltreatment and the
      occurrence of GAD.

PMID- 23951266
TI  - A comparison of the performance of the I-gelTM vs. the LMA-STMduring anesthesia:
      a meta-analysis of randomized controlled trials.
AB  - BACKGROUND AND OBJECTIVE: Conflicting results were found between the I-gelTM and
      the LMA-SupremeTM during anesthesia, so we conducted a meta-analysis of
      randomized controlled trials (RCTs) to compare the effectiveness and safety of
      the I-gelTM vs. the LMA-SupremeTMduring anesthesia. METHODS: A comprehensive
      search was conducted using Pubmed, EMbase, ISI Web of Knowledge, the Cochrane
      Library, China Journal Full-text Database, Chinese Biomedical Database, Chinese
      Scientific Journals Full-text Database, CMA Digital Periodicals, and Google
      scholar to find RCTs that compare the LMA-STM with the i-gelTMduring anesthesia.
      Two reviewers independently selected trials, extracted data, and assessed the
      methodological qualities and evidence levels. Data were analyzed by RevMan 5.0
      and comprehensive meta-analysis software. RESULTS: Ten RCTs were included. There
      were no significant differences in oropharyngeal leak pressures (mean difference
      [MD] 0.72, 95% confidence interval [CI] -1.10 2.53), device placement time (MD 
      1.3, 95%CI -4.07 1.44), first attempt insertion success (risk ratio [RR] 1.01,
      95% CI 0.9 1.14), grade 3 and 4 fiberoptic view (RR 0.89, 95%CI 0.65 1.21), and
      blood on removal (RR 0.62, 95%CI 0.32 1.22) between the i-gelTM and the LMA
      SupremeTM, respectively. However, the LMA-SupremeTMwas associated with easier
      gastric tube insertion (RR 1.17, 95%CI 1.07 1.29), and more sore throat (RR 2.56,
      95%CI 1.60 4.12) than the i-gelTM group. CONCLUSIONS: The LMA-SupremeTM and i
      gelTM were similarly successful and rapidly inserted. However, the LMA-SupremeTM
      was shown to be easier for gastric tube insertion and associated with more sore
      throat compared with the i-gelTM.

PMID- 23951267
TI  - Clinical signs of radiologic pneumonia in under-five hypokalemic diarrheal
      children admitted to an urban hospital in bangladesh.
AB  - BACKGROUND: Clinical signs of pneumonia are often veiled in under-five diarrheal
      children presenting with hypokalemia, making clinical diagnosis of pneumonia very
      difficult in such population. However, there is no published report that
      describes the influences of hypokalemia on the clinical signs of pneumonia in
      diarrheal children. Our objective was to assess the influences of hypokalemia,
      and their outcome in such children. METHODS: We prospectively enrolled all under
      five diarrheal children (n = 180) admitted to the Special Care Ward of the Dhaka
      Hospital of icddr,b from September-December 2007 with radiological pneumonia who
      also had their serum potassium estimated. We compared the clinical features and
      outcome of the diarrheal children having pneumonia with (cases = 55) and without
      hypokalemia (controls = 125). RESULTS: The case-fatality among the cases was 2
      times higher compared to the controls, but the difference was not statistically
      significant (p = 0.202). In logistic regression analysis, after adjusting for
      potential confounders such as age of the patient, clinical dehydration, severe
      wasting, abnormally sleepy, lower chest wall in-drawing, nasal flaring and
      inability to drink on admission, under-five diarrheal children with pneumonia who
      presented with nutritional edema had 3 times more risk to have hypokalemia
      compared to those without nutritional edema (OR = 2.76, 95% CI = 1.01-7.51) and
      these hypokalemic children were 64% less likely to present with fast breathing
      (OR = 0.36, 95% CI = 0.17-0.74). CONCLUSION AND SIGNIFICANCE: The results of our
      analysis are simple but may have great public health implications and underscore
      the importance of diligent assessment for pneumonia in under-five diarrheal
      children having risk of hypokalemia as in children with nutritional edema even in
      absence of fast breathing, a useful sign of pneumonia. This may help for early
      initiation of first dose of parental antibiotics along with potassium
      supplementation before referral to tertiary hospitals by health workers to combat
      probability of deaths in such population especially in resource limited settings.

PMID- 23951268
TI  - SLC1A2 variant is associated with essential tremor in Taiwanese population.
AB  - Essential tremor (ET), which is one of the most common movement disorders, may
      lead to severe interference in quality of life. The first genome-wide association
      study (GWAS) has identified an association of the LINGO1 variant (rs9652490) with
      ET in Americans and Europeans. Recently, a second GWAS that was performed in a
      European population has discovered a new variant (rs3794087) of the main glial
      glutamate transporter (SLC1A2) that increases the risk of ET with an odds ratio
      of about 1.4. SLC1A2 encodes for the major glial high-affinity glutamate reuptake
      transporter in the brain and is a potential ET susceptibility gene. Because
      replication in a different ethnic population is important for validating a
      finding, we conducted a case-control study to investigate the SLC1A2 variant in
      an Asian cohort with ET in Taiwan. A total of 542 subjects (273 ET patients and
      269 controls) were included. The results showed that rs3794087 was associated
      with ET among the Taiwanese. The odds ratio was 1.37. Our results were similar to
      those of the second GWAS of ET in Europeans, and this confirms that SLC1A2 may be
      a good functional candidate gene for ET. A replication study in another
      independent population is of importance to validate this association. 

PMID- 23951269
TI  - The effect of the physical presence of co-players on perceived ostracism and
      event-related brain potentials in the cyberball paradigm.
AB  - The affective and cognitive mechanisms elicited by the experience of social
      exclusion-or ostracism-have recently been explored using behavioral and
      neurocognitive methods. Most of the studies took advantage of the Cyberball
      paradigm, a virtual ball tossing game with presumed co-players connected via the
      internet. Consistent behavioral findings indicate that exclusion obviously
      threatens fundamental social needs (belonging, self-esteem, meaningful existence,
      and control) and lowers mood. In this study, we followed the question whether the
      credibility of the setting affects the processing of social exclusion. In
      contrast to a control group (standard Cyberball setup), co-players were
      physically present in an experimental group. Although the credibility of the
      virtual ball tossing game was significantly enhanced in the experimental group,
      self-reported negative mood and need threat were not enhanced compared to the
      control group. Event-related brain potentials (ERPs), however, indicated a
      differential processing of social exclusion. The N2 amplitude triggered by
      occasional ball receptions was significantly reduced in the experimental group.
      This effect was restricted for an early time range (130-210 ms), and did not
      extend to the following P3 components. The ERP effect in the N2 time range can be
      related to a differential social reward processing in ostracism if co-players are
      physically present. The lack of a corresponding correlate in the behavioral data
      indicates that some facets of ostracism processing are not covered by
      questionnaire data. 

PMID- 23951270
TI  - Economic evaluation of a problem solving intervention to prevent recurrent
      sickness absence in workers with common mental disorders.
AB  - OBJECTIVES: Workers with common mental disorders (CMDs) frequently experience
      recurrent sickness absence but scientifically evaluated interventions to prevent
      recurrences are lacking. The objectives of this study are to evaluate the cost
      effectiveness and cost-benefit of a problem solving intervention aimed at
      preventing recurrent sickness absence in workers with CMDs compared to care as
      usual. METHODS: An economic evaluation was conducted alongside a cluster
      randomised controlled trial with 12 months follow-up. Treatment providers were
      randomised to either a 2-day training in the SHARP-at work intervention, i.e. a
      problem solving intervention, or care as usual. Effect outcomes were the
      incidence of recurrent sickness absence and time to recurrent sickness absence.
      Self-reported health care utilisation was measured by questionnaires. A cost
      effectiveness analysis (CEA) from the societal perspective and a cost-benefit
      analysis (CBA) from the employer's perspective were conducted. RESULTS: The CEA
      showed that the SHARP-at work intervention was more effective but also more
      expensive than care as usual. The CBA revealed that employer's occupational
      health care costs were significantly higher in the intervention group compared to
      care as usual. Overall, the SHARP-at work intervention showed no economic benefit
      compared to care as usual. CONCLUSIONS: As implementation of the SHARP-at work
      intervention might require additional investments, health care policy makers need
      to decide if these investments are worthwhile considering the results that can be
      accomplished in reducing recurrent sickness absence.

PMID- 23951271
TI  - Characterization of genetic determinants that modulate Candida albicans
      filamentation in the presence of bacteria.
AB  - In the human body, fungi and bacteria share many niches where the close contact
      of these organisms maintains a balance among the microbial population. However,
      when this microbial balance is disrupted, as with antibiotic treatment, other
      bacteria or fungi can grow uninhibited. C. albicans is the most common
      opportunistic fungal pathogen affecting humans and can uniquely control its
      morphogenesis between yeast, pseudohyphal, and hyphal forms. Numerous studies
      have shown that C. albicans interactions with bacteria can impact its ability to
      undergo morphogenesis; however, the genetics that govern this morphological
      control via these bacterial interactions are still relatively unknown. To aid in
      the understanding of the cross-kingdom interactions of C. albicans with bacteria
      and the impact on morphology we utilized a haploinsufficiency based C. albicans
      mutant screen to test for the ability of C. albicans to produce hyphae in the
      presence of three bacterial species (Escherichia coli, Pseudomonas aeruginosa,
      and Staphylococcus aureus). Of the 18,144 mutant strains tested, 295 mutants
      produced hyphae in the presence of all three bacterial species. The 295 mutants
      identified 132 points of insertion, which included identified/predicted genes,
      major repeat sequences, and a number of non-coding/unannotated transcripts. One
      gene, CDR4, displayed increased expression when co-cultured with S. aureus, but
      not E. coli or P. aeruginosa. Our data demonstrates the ability to use a large
      scale library screen to identify genes involved in Candida-bacterial interactions
      and provides the foundation for comprehending the genetic pathways relating to
      bacterial control of C. albicans morphogenesis. 

PMID- 23951272
TI  - Direct reciprocity in spatial populations enhances R-reciprocity as well as ST
      reciprocity.
AB  - As is well-known, spatial reciprocity plays an important role in facilitating the
      emergence of cooperative traits, and the effect of direct reciprocity is also
      obvious for explaining the cooperation dynamics. However, how the combination of
      these two scenarios influences cooperation is still unclear. In the present work,
      we study the evolution of cooperation in 2 * 2 games via considering both spatial
      structured populations and direct reciprocity driven by the strategy with 1
      memory length. Our results show that cooperation can be significantly facilitated
      on the whole parameter plane. For prisoner's dilemma game, cooperation dominates
      the system even at strong dilemma, where maximal social payoff is still realized.
      In this sense, R-reciprocity forms and it is robust to the extremely strong
      dilemma. Interestingly, when turning to chicken game, we find that ST-reciprocity
      is also guaranteed, through which social average payoff and cooperation is
      greatly enhanced. This reciprocity mechanism is supported by mean-field analysis
      and different interaction topologies. Thus, our study indicates that direct
      reciprocity in structured populations can be regarded as a more powerful factor
      for the sustainability of cooperation.

PMID- 23951273
TI  - Stock market returns and clinical trial results of investigational compounds: an
      event study analysis of large biopharmaceutical companies.
AB  - BACKGROUND: For biopharmaceutical companies, investments in research and
      development are risky, and the results from clinical trials are key inflection
      points in the process. Few studies have explored how and to what extent the
      public equity market values clinical trial results. METHODS: Our study dataset
      matched announcements of clinical trial results for investigational compounds
      from January 2011 to May 2013 with daily stock market returns of large United
      States-listed pharmaceutical and biotechnology companies. Event study methodology
      was used to examine the relationship between clinical research events and changes
      in stock returns. RESULTS: We identified public announcements for clinical trials
      of 24 investigational compounds, including 16 (67%) positive and 8 (33%) negative
      events. The majority of announcements were for Phase 3 clinical trials (N = 13,
      54%), and for oncologic (N = 7, 29%) and neurologic (N = 6, 24%) indications. The
      median cumulative abnormal returns on the day of the announcement were 0.8% (95%
      confidence interval [CI]: -2.3, 13.4%; P = 0.02) for positive events and -2.0%
      (95% CI: -9.1, 0.7%; P = 0.04) for negative events, with statistically
      significant differences from zero. In the day immediately following the
      announcement, firms with positive events were associated with stock price
      corrections, with median cumulative abnormal returns falling to 0.4% (95% CI: 
      3.8, 12.3%; P = 0.33). For firms with negative announcements, the median
      cumulative abnormal returns were -1.7% (95% CI: -9.5, 1.0%; P = 0.03), and
      remained significantly negative over the two day event window. The magnitude of
      abnormal returns did not differ statistically by indication, by trial phase, or
      between biotechnology and pharmaceutical firms. CONCLUSIONS: The release of
      clinical trial results is an economically significant event and has meaningful
      effects on market value for large biopharmaceutical companies. Stock return
      underperformance due to negative events is greater in magnitude and persists
      longer than abnormal returns due to positive events, suggesting asymmetric market
      reactions.

PMID- 23951274
TI  - Working memory in ALS patients: preserved performance but marked changes in
      underlying neuronal networks.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
      which affects the motor system but also other frontal brain regions. In this
      study we investigated changes in functional neuronal networks including posterior
      brain regions that are not directly affected by the neurodegenerative process. To
      this end, we analyzed the contralateral delay activity (CDA), an ERP component
      considered an online marker of memory storage in posterior cortex, while 23 ALS
      patients and their controls performed a delayed-matching-to-sample working memory
      (WM) task. The task required encoding of stimuli in the cued hemifield whilst
      ignoring stimuli in the other hemifield. Despite their unimpaired behavioral
      performance patients displayed several changes in the neuronal markers of the
      memory processes. Their CDA amplitude was smaller; it showed less load-dependent
      modulation and lacked the reduction observed when controls performed the same
      task three months later. The smaller CDA in the patients could be attributed to
      more ipsilateral cortical activity which may indicate that ALS patients
      unnecessarily processed the irrelevant stimuli as well. The latter is presumably
      related to deterioration of the frontal cortex in the patient group which was
      indicated by slight deficits in tests of their executive functions that increased
      over time. The frontal pathology presumably affected their top-down control of
      memory storage in remote regions in the posterior brain. In sum, the present
      results demonstrate functional changes in neuronal networks, i.e.
      neuroplasticity, in ALS that go well beyond the known structural changes. They
      also show that at least in WM tasks, in which strategic top-down control demands
      are relatively low, the frontal deficit can be compensated for by intact low
      level processes in posterior brain regions. 

PMID- 23951275
TI  - Metabolic characteristics and response to high altitude in Phrynocephalus
      erythrurus (Lacertilia: Agamidae), a lizard dwell at altitudes higher than any
      other living lizards in the world.
AB  - Metabolic response to high altitude remains poorly explored in reptiles. In the
      present study, the metabolic characteristics of Phrynocephaluserythrurus
      (Lacertilia: Agamidae), which inhabits high altitudes (4500 m) and
      Phrynocephalusprzewalskii (Lacertilia: Agamidae), which inhabits low altitudes,
      were analysed to explore the metabolic regulatory strategies for lizards living
      at high-altitude environments. The results indicated that the mitochondrial
      respiratory rates of P. erythrurus were significantly lower than those of P.
      przewalskii, and that proton leak accounts for 74~79% of state 4 and 7~8% of
      state3 in P. erythrurus vs. 43~48% of state 4 and 24~26% of state3 in P.
      przewalskii. Lactate dehydrogenase (LDH) activity in P. erythrurus was lower than
      in P. przewalskii, indicating that at high altitude the former does not,
      relatively, have a greater reliance on anaerobic metabolism. A higher activity
      related to beta-hydroxyacyl coenzyme A dehydrogenase (HOAD) and the HOAD/citrate
      synthase (CS) ratio suggested there was a possible higher utilization of fat in
      P. erythrurus. The lower expression of PGC-1alpha and PPAR-gamma in P. erythrurus
      suggested their expression was not influenced by cold and low PO2 at high
      altitude. These distinct characteristics of P. erythrurus are considered to be
      necessary strategies in metabolic regulation for living at high altitude and may
      effectively compensate for the negative influence of cold and low PO2. 

PMID- 23951276
TI  - Sex differences in the beneficial cardiac effects of chronic treatment with
      atrial natriuretic Peptide in spontaneously hypertensive rats.
AB  - INTRODUCTION: The aim of this study was to investigate both the effects of
      chronic treatment with atrial natriuretic peptide (ANP) on systolic blood
      pressure (SBP), cardiac nitric oxide (NO) system, oxidative stress, hypertrophy,
      fibrosis and apoptosis in spontaneously hypertensive rats (SHR), and sex-related
      differences in the response to the treatment. METHODS: 10 week-old male and
      female SHR were infused with ANP (100 ng/hr/rat) or saline (NaCl 0.9%) for 14
      days (subcutaneous osmotic pumps). SBP was recorded and nitrites and nitrates
      excretion (NOx) were determined. After treatment, NO synthase (NOS) activity,
      eNOS expression, thiobarbituric acid-reactive substances (TBARS) and glutathione
      concentration were determined in left ventricle, as well as the activity of
      glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD).
      Morphological studies in left ventricle were performed in slices stained with
      hematoxylin-eosin or Sirius red to identify collagen as a fibrosis indicator;
      immunohistochemistry was employed for identification of transforming growth
      factor beta; and apoptosis was evaluated by Tunel assay. RESULTS: Female SHR
      showed lower SBP, higher NO-system activity and less oxidative stress, fibrosis
      and hypertrophy in left ventricle, as well as higher cardiac NOS activity, eNOS
      protein content and NOx excretion than male SHR. Although ANP treatment lowered
      blood pressure and increased NOS activity and eNOS expression in both sexes,
      cardiac NOS response to ANP was more marked in females. In left ventricle, ANP
      reduced TBARS and increased glutathione concentration and activity of CAT and SOD
      enzymes in both sexes, as well as GPx activity in males. ANP decreased fibrosis
      and apoptosis in hearts from male and female SHR but females showed less end
      organ damage in heart. Chronic ANP treatment would ameliorate hypertension and
      end-organ damage in heart by reducing oxidative stress, increasing NO-system
      activity, and diminishing fibrosis and hypertrophy.

PMID- 23951277
TI  - Fertilization induces a transient exposure of phosphatidylserine in mouse eggs.
AB  - Phosphatidylserine (PS) is normally localized to the inner leaflet of the plasma
      membrane and the requirement of PS translocation to the outer leaflet in cellular
      processes other than apoptosis has been demonstrated recently. In this work we
      investigated the occurrence of PS mobilization in mouse eggs, which express
      flippase Atp8a1 and scramblases Plscr1 and 3, as determined by RT-PCR; these
      enzyme are responsible for PS distribution in cell membranes. We find a dramatic
      increase in binding of flouresceinated-Annexin-V, which specifically binds to PS,
      following fertilization or parthenogenetic activation induced by SrCl2 treatment.
      This increase was not observed when eggs were first treated with BAPTA-AM,
      indicating that an increase in intracellular Ca(2+) concentration was required
      for PS exposure. Fluorescence was observed over the entire egg surface with the
      exception of the regions overlying the meiotic spindle and sperm entry site. PS
      exposure was also observed in activated eggs obtained from CaMKIIgamma null
      females, which are unable to exit metaphase II arrest despite displaying Ca(2+)
      spikes. In contrast, PS exposure was not observed in TPEN-activated eggs, which
      exit metaphase II arrest in the absence of Ca(2+) release. PS exposure was also
      observed when eggs were activated with ethanol but not with a Ca(2+) ionophore,
      suggesting that the Ca(2+) source and concentration are relevant for PS exposure.
      Last, treatment with cytochalasin D, which disrupts microfilaments, or
      jasplakinolide, which stabilizes microfilaments, prior to egg activation showed
      that PS externalization is an actin-dependent process. Thus, the Ca(2+) rise
      during egg activation results in a transient exposure of PS in fertilized eggs
      that is not associated with apoptosis. 

PMID- 23951279
TI  - The good, the bad, and the ugly: the influence of skull reconstructions and
      intraspecific variability in studies of cranial morphometrics in theropods and
      Basal saurischians.
AB  - Several studies investigating macroevolutionary skull shape variation in fossil
      reptiles were published recently, often using skull reconstructions taken from
      the scientific literature. However, this approach could be potentially
      problematic, because skull reconstructions might differ notably due to
      incompleteness and/or deformation of the material. Furthermore, the influence of
      intraspecific variation has usually not been explored in these studies. Both
      points could influence the results of morphometric analyses by affecting the
      relative position of species to each other within the morphospace. The aim of the
      current study is to investigate the variation in morphometric data between skull
      reconstructions based on the same specimen, and to compare the results to shape
      variation occurring in skull reconstructions based on different specimens of the
      same species (intraspecific variation) and skulls of closely related species
      (intraspecific variation). Based on the current results, shape variation of
      different skull reconstructions based on the same specimen seems to have
      generally little influence on the results of a geometric morphometric analysis,
      although it cannot be excluded that some erroneous reconstructions of poorly
      preserved specimens might cause problems occasionally. In contrast, for different
      specimens of the same species the variation is generally higher than between
      different reconstructions based on the same specimen. For closely related
      species, at least with similar ecological preferences in respect to the dietary
      spectrum, the degree of interspecific variation can overlap with that of
      intraspecific variation, most probably due to similar biomechanical constraints. 

PMID- 23951278
TI  - Physical exercise performance in temperate and warm environments is decreased by
      an impaired arterial baroreflex.
AB  - The present study aimed to investigate whether running performance in different
      environments is dependent on intact arterial baroreceptor reflexes. We also
      assessed the exercise-induced cardiovascular and thermoregulatory responses in
      animals lacking arterial baroafferent signals. To accomplish these goals, male
      Wistar rats were subjected to sinoaortic denervation (SAD) or sham surgery (SHAM)
      and had a catheter implanted into the ascending aorta to record arterial pressure
      and a telemetry sensor implanted in the abdominal cavity to record core
      temperature. After recovering from these surgeries, the animals were subjected to
      constant- or incremental-speed exercises performed until the voluntary
      interruption of effort under temperate (25 degrees  C) and warm (35 degrees  C)
      conditions. During the constant-speed exercises, the running time until the rats
      were fatigued was shorter in SAD rats in both environments. Although the core
      temperature was not significantly different between the groups, tail skin
      temperature was higher in SAD rats under temperate conditions. The denervated
      rats also displayed exaggerated increases in blood pressure and double product
      compared with the SHAM rats; in particular, in the warm environment, these
      exaggerated cardiovascular responses in the SAD rats persisted until they were
      fatigued. These SAD-mediated changes occurred in parallel with increased
      variability in the very low and low components of the systolic arterial pressure
      power spectrum. The running performance was also affected by SAD during the
      incremental-speed exercises, with the maximal speed attained being decreased by
      approximately 20% in both environments. Furthermore, at the maximal power output
      tolerated during the incremental exercises, the mean arterial pressure, heart
      rate and double product were exaggerated in the SAD relative to SHAM rats. In
      conclusion, the chronic absence of the arterial baroafferents accelerates
      exercise fatigue in temperate and warm environments. Our findings also suggest
      that an augmented cardiovascular strain accounted for the early interruption of
      exercise in the SAD rats. 

PMID- 23951280
TI  - Monitoring monoclonal antibody delivery in oncology: the example of bevacizumab.
AB  - Developing therapeutic monoclonal antibodies paves the way for new strategies in
      oncology using targeted therapy which should improve specificity. However, due to
      a lack of biomarkers, a personalized therapy scheme cannot always be applied with
      monoclonal antibodies. As a consequence, the efficacy or side effects associated
      with this type of treatment often appear to be sporadic. Bevacizumab is a
      therapeutic monoclonal antibody targeting Vascular Endothelial Growth Factor
      (VEGF). It is used to limit tumor vascularization. No prognosis or response
      biomarker is associated with this antibody, we therefore assessed whether the
      administration protocol could be a possible cause of heterogeneous responses (or
      variable efficacy). To do this, we developed a bevacizumab assay with a broad
      sensitivity range to measure blood bevacizumab concentrations. We then analyzed
      bevacizumab concentrations in 17 patients throughout the first quarter of
      treatment. In line with previously published data, average blood concentrations
      were 88+/-27 mg/L following the first dose administered, and 213+/-105 mg/L after
      the last (6(th)) dose administered. However, the individual values were
      scattered, with a mean 4-fold difference between the lowest and the highest
      concentration for each dose administered. We demonstrated that the bevacizumab
      administration schedule results in a high inter-individual variability in terms
      of blood concentrations. Comparison of assay data with clinical data indicates
      that blood concentrations above the median are associated with side effects,
      whereas values below the median favor inefficacy. In conclusion, bevacizumab
      based therapy could benefit from a personalized administration schedule including
      follow-up and adjustment of circulating bevacizumab concentrations. 

PMID- 23951281
TI  - The comparison of the effects of three physiotherapy techniques on hamstring
      flexibility in children: a prospective, randomized, single-blind study.
AB  - The aim of the study was to evaluate changes in hamstring flexibility in 120
      asymptomatic children who participated in a 6-week program consisting of one
      physiotherapy session per week and daily home exercises. The recruitment criteria
      included age (10-13 years), no pain, injury or musculoskeletal disorder
      throughout the previous year, physical activity limited to school sport. Subjects
      were randomly assigned to one of the three groups: (1) post-isometric relaxation 
      PIR (n = 40), (2) static stretch combined with stabilizing exercises - SS (n =
      40) and (3) stabilizing exercises - SE (n = 40). Hamstring flexibility was
      assessed with straight leg raise (SLR), popliteal angle (PA) and finger-to-floor
      (FTF) tests. The examinations were conducted by blinded observers twice, prior to
      the program and a week after the last session with the physiotherapist. Twenty
      six children who did not participate in all six exercise sessions with
      physiotherapists were excluded from the analysis. The results obtained by 94
      children were analyzed (PIR, n = 32; SS, n = 31; SE, n = 31). In the PIR and SS
      groups, a significant (P<0.01) increase in SLR, PA, FTF results was observed. In
      the SE group, a significant (P<0.001) increase was observed in the SLR but not in
      the PA and FTF (P>0.05). SLR result in the PIR and SS groups was significantly
      (P<0.001) higher than in the SE group. As far as PA results are concerned, a
      significant difference was observed only between the SS and SE groups (P =
      0.014). There were no significant (P = 0.15) differences regarding FTF results
      between the three groups. Post-isometric muscle relaxation and static stretch
      with stabilizing exercises led to a similar increase in hamstring flexibility and
      trunk forward bend in healthy 10-13-year-old children. The exercises limited to
      straightening gluteus maximus improved the SLR result, but did not change the PA
      and FTF results. 

PMID- 23951283
TI  - Application of body mass index according to height-age in short and tall
      children.
AB  - BACKGROUND: In children with either delayed or accelerated growth, expressing the
      body mass index (BMI) to chronological age might lead to invalid body composition
      estimates. Reference to height-age has been suggested for such populations;
      however its validity has not been demonstrated. METHODS: Anthropometric data of
      healthy children were obtained from the German KiGGS survey. We selected three
      samples with different height distributions representing short stature (mean
      height SDS: -1.6), normal stature (height SDS: 0), and tall stature (height SDS:
      +1.6), and compared BMI-for-age and BMI-for-height-age between these samples
      across the paediatric age range. Differences between samples were tested using
      Kruskal-Wallis one-way analysis of variance and permutation tests. RESULTS: At a
      given age, BMI was distributed towards lower values in short, and towards higher
      values in tall subjects as compared to a population with average height
      distribution. Expressing BMI to height-age eliminated these differences in boys
      with a short stature from 4 years to 14 years of age, in tall boys from 4 to 16
      years, in short girls aged 2-10 years or tall girls aged 2-17 years. CONCLUSION:
      From late infancy to adolescent age, BMI distribution co-varies with height
      distribution and referencing to height-age appears appropriate within this age
      period. However, caution is needed when data about pubertal status are absent.

PMID- 23951282
TI  - Us3 kinase encoded by herpes simplex virus 1 mediates downregulation of cell
      surface major histocompatibility complex class I and evasion of CD8+ T cells.
AB  - Detection and elimination of virus-infected cells by CD8(+) cytotoxic T
      lymphocytes (CTLs) depends on recognition of virus-derived peptides presented by
      major histocompatibility complex class I (MHC-I) molecules on the surface of
      infected cells. In the present study, we showed that inactivation of the activity
      of viral kinase Us3 encoded by herpes simplex virus 1 (HSV-1), the etiologic
      agent of several human diseases and a member of the alphaherpesvirinae,
      significantly increased cell surface expression of MHC-I, thereby augmenting CTL
      recognition of infected cells in vitro. Overexpression of Us3 by itself had no
      effect on cell surface expression of MHC-I and Us3 was not able to phosphorylate
      MHC-I in vitro, suggesting that Us3 indirectly downregulated cell surface
      expression of MHC-I in infected cells. We also showed that inactivation of Us3
      kinase activity induced significantly more HSV-1-specific CD8(+) T cells in mice.
      Interestingly, depletion of CD8(+) T cells in mice significantly increased
      replication of a recombinant virus encoding a kinase-dead mutant of Us3, but had
      no effect on replication of a recombinant virus in which the kinase-dead mutation
      was repaired. These results indicated that Us3 kinase activity is required for
      efficient downregulation of cell surface expression of MHC-I and mediates evasion
      of HSV-1-specific CD8(+) T cells. Our results also raised the possibility that
      evasion of HSV-1-specific CD8(+) T cells by HSV-1 Us3-mediated inhibition of MHC
      I antigen presentation might in part contribute to viral replication in vivo. 

PMID- 23951284
TI  - Increased serum oxidative stress markers in women with uterine leiomyoma.
AB  - BACKGROUND: Uterine leiomyomas (fibroids) are the most common gynaecological
      benign tumors in premenopausal women. Evidences support the role of oxidative
      stress in the development of uterine leiomyoma. We have analysed oxidative stress
      markers (thiols, advanced oxidized protein products (AOPP), protein carbonyls and
      nitrates/nitrites) in preoperative sera from women with histologically proven
      uterine leiomyoma. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a laboratory
      study in a tertiary-care university hospital. Fifty-nine women with
      histologically proven uterine leiomyoma and ninety-two leiomyoma-free control
      women have been enrolled in this study. Complete surgical exploration of the
      abdominopelvic cavity was performed in each patient. Preoperative serum samples
      were obtained from all study participants to assay serum thiols, AOPP, protein
      carbonyls and nitrates/nitrites. Concentrations of serum protein carbonyl groups
      and AOPP were higher in leiomyoma patients than in the control group (p=0.005 and
      p<0.001, respectively). By contrast, serum thiol levels were lower in leiomyoma
      patients (p<0.001). We found positive correlations between serum AOPP
      concentrations and total fibroids weight (r=0.339; p=0.028), serum AOPP and serum
      protein carbonyls with duration of infertility (r=0.762; p=0.006 and r=0.683;
      p=0.021, respectively). CONCLUSIONS/SIGNIFICANCE: This study, for the first time,
      reveals a significant increase of protein oxidative stress status and reduced
      antioxidant capacity in sera from women with uterine leiomyoma.

PMID- 23951285
TI  - Development of multiplex PCR assays for the identification of the 33 serotypes of
      Streptococcus suis.
AB  - Streptococcussuis is an important zoonotic agent causing severe diseases in pigs
      and humans. To date, 33 serotypes of S. suis have been identified based on
      antigenic differences in the capsular polysaccharide. The capsular polysaccharide
      synthesis (cps) locus encodes proteins/enzymes that are responsible for capsular
      production and variation in the capsule structures are the basis of S. suis
      serotyping. Multiplex and/or simplex PCR assays have been developed for 15
      serotypes based on serotype-specific genes in the cps gene cluster. In this
      study, we developed a set of multiplex PCR (mPCR) assays to identify the 33
      currently known S. suis serotypes. To identify serotype-specific genes for mPCR,
      the entire genomes of reference strains for the 33 serotypes were sequenced using
      whole genome high-throughput sequencing, and the cps gene clusters from these
      strains were identified and compared. We developed a set of 4 mPCR assays based
      on the polysaccharide polymerase gene wzy, one of the serotype-specific genes.
      The assays can identify all serotypes except for two pairs of serotypes: 1 and
      14, and 2 and 1/2, which have no serotype-specific genes between them. The first
      assay identifies 12 serotypes (serotypes 1 to 10, 1/2, and 14) that are the most
      frequently isolated from diseased pigs and patients; the second identifies 10
      serotypes (serotypes 11 to 21 except 14); the third identifies the remaining 11
      serotypes (serotypes 22 to 31, and 33); and the fourth identifies a new cps
      cluster of S. suis discovered in this study in 16 isolates that agglutinated with
      antisera for serotypes 29 and 21. The multiplex PCR assays developed in this
      study provide a rapid and specific method for molecular serotyping of S. suis. 

PMID- 23951286
TI  - Bioenergetic and antiapoptotic properties of mitochondria from cultured human
      prostate cancer cell lines PC-3, DU145 and LNCaP.
AB  - The purpose of this work was to reveal the metabolic features of mitochondria
      that might be essential for inhibition of apoptotic potential in prostate cancer
      cells. We studied mitochondria isolated from normal prostate epithelial cells
      (PrEC), metastatic prostate cancer cell lines LNCaP, PC-3, DU145; and non
      prostate cancer cells - human fibrosarcoma HT1080 cells; and normal human
      lymphoblastoid cells. PrEC cells contained 2 to 4 times less mitochondria per
      gram of cells than the three PC cell lines. Respiratory activities of PrEC cell
      mitochondria were 5-20-fold lower than PC mitochondria, depending on substrates
      and the metabolic state, due to lower content and lower activity of the
      respiratory enzyme complexes. Mitochondria from the three metastatic prostate
      cancer cell lines revealed several features that are distinctive only to these
      cells: low affinity of Complex I for NADH, 20-30 mV higher electrical membrane
      potential (DeltaPsi). Unprotected with cyclosporine A (CsA) the PC-3 mitochondria
      required 4 times more Ca2+ to open the permeability transition pore (mPTP) when
      compared with the PrEC mitochondria, and they did not undergo swelling even in
      the presence of alamethicin, a large pore forming antibiotic. In the presence of
      CsA, the PC-3 mitochondria did not open spontaneously the mPTP. We conclude that
      the low apoptotic potential of the metastatic PC cells may arise from inhibition
      of the Ca2+-dependent permeability transition due to a very high DeltaPsi and
      higher capacity to sequester Ca2+. We suggest that due to the high DeltaPsi,
      mitochondrial metabolism of the metastatic prostate cancer cells is predominantly
      based on utilization of glutamate and glutamine, which may promote development of
      cachexia.

PMID- 23951287
TI  - Coping with heat: function of the natal coat of cape fur seal (Arctocephalus
      Pusillus Pusillus) pups in maintaining core body temperature.
AB  - Cape fur seal (Arctocephalus pusillus) pups spend the first weeks of life
      exclusively or mainly ashore. They are exposed to intense solar radiation and
      high temperatures for long time periods, which results in temperatures up to at
      least 80 degrees C on their black natal coat. To test the hypothesis that the
      natal coat has a crucial function in coping with these extreme conditions, we
      investigated the insulating properties of the natal coat in six captive newborn
      Cape fur seals during the first 50 days after birth. The natal fur differs from
      the adult fur not only in colour, but also in density, structure, and water
      repellence. We measured temperature on the fur surface and within the fur, as
      well as skin and rectal temperature under varying environmental conditions,
      comparable to the species' habitat. Experiments were designed to not influence
      the spontaneous behaviour of the pups. Rectal temperature was constant as long as
      the pups stayed dry, even during long-lasting intense solar radiation for up to 3
      h. Skin temperature remained close to rectal temperature as long as the fur was
      dry, while with wet fur, skin temperature was significantly reduced as well. Our
      results show that the natal coat provides an effective insulation against
      overheating. The severely reduced insulation of wet natal fur against cold
      supports the assumption that the natal fur is an adaptation to the pups'
      terrestrial phase of life. 

PMID- 23951288
TI  - A comparative genome analysis of PME and PMEI families reveals the evolution of
      pectin metabolism in plant cell walls.
AB  - Pectins are fundamental polysaccharides in the plant primary cell wall. Pectins
      are synthesized and secreted to cell walls as highly methyl-esterified polymers
      and then demethyl-esterified by pectin methylesterases (PMEs), which are
      spatially regulated by pectin methylesterase inhibitors (PMEIs). Although PME and
      PMEI genes are pivotal in plant cell wall formation, few studies have focused on
      the evolutionary patterns of the PME and PMEI gene families. In this study, the
      gene origin, evolution, and expression diversity of these two families were
      systematically analyzed using 11 representative species, including algae,
      bryophytes, lycophytes and flowering land plants. The results show that 1) for
      the two subfamilies (PME and proPME) of PME, the origin of the PME subfamily is
      consistent with the appearance of pectins in early charophyte cell walls, 2)
      Whole genome duplication (WGD) and tandem duplication contribute to the expansion
      of proPME and PMEI families in land plants, 3) Evidence of selection pressure
      shows that the proPME and PMEI families have rapidly evolved, particularly the
      PMEI family in vascular plants, and 4) Comparative expression profile analysis of
      the two families indicates that the eudicot Arabidopsis and monocot rice have
      different expression patterns. In addition, the gene structure and sequence
      analyses show that the origin of the PMEI domain may be derived from the
      neofunctionalization of the pro domain after WGD. This study will advance the
      evolutionary understanding of the PME and PMEI families and plant cell wall
      development. 

PMID- 23951289
TI  - Cowpeas in Northern Ghana and the factors that predict caregivers' intention to
      give them to schoolchildren.
AB  - BACKGROUND: Cowpeas are important staple legumes among the rural poor in northern
      Ghana. Our objectives were to assess the iron and zinc content of cowpea
      landraces and identify factors that predict the intention of mothers/caregivers
      to give cowpeas to their schoolchildren. METHODS AND FINDINGS: We performed
      biochemical analysis on 14 landraces of cowpeas and assessed the opinion of 120
      caregiver-child pairs on constructs based on the combined model of the Theory of
      Planned Behaviour and Health Belief Model. We used correlations and multiple
      regressions to measure simple associations between constructs and identify
      predictive constructs. Cowpea landraces contained iron and zinc in the range of
      4.9-8.2 mg/100 g d.w and 2.7-4.1 mg/100 g d.w respectively. The landraces also
      contained high amounts of phytate (477-1110 mg/100 g d.w) and polyphenol (327
      1055 mg/100 g d.w). Intention of mothers was strongly associated (rs = 0.72,
      P<0.001) with and predicted (beta = 0.63, P<0.001) behaviour. The constructs,
      barriers (beta = -0.42, P = 0.001) and attitudes towards behaviour (beta = 0.25,
      P<0.028), significantly predicted intention albeit the predictive ability of the
      model was weak. CONCLUSIONS: We conclude that some cowpea landraces from northern
      Ghana have appreciable amounts of iron and zinc but probably with poor
      bioavailability. Attitudes towards giving cowpeas and perception of barriers are
      important predictors of caregivers' intention to give cowpeas to their
      schoolchildren. Finally our results suggest that increasing knowledge on
      nutritional benefits of cowpeas may increase health values caregivers hold for
      their children in support of giving cowpeas to schoolchildren.

PMID- 23951290
TI  - PCSK9 prosegment chimera as novel inhibitors of LDLR degradation.
AB  - The proprotein convertase PCSK9, a target for the treatment of
      hypercholesterolemia, is a negative regulator of the LDL receptor (LDLR) leading
      to its degradation in endosomes/lysosomes and up-regulation of plasma LDL
      cholesterol levels. The proprotein convertases, a family of nine secretory serine
      proteases, are first synthesized as inactive zymogens. Except for PCSK9, all
      other convertases are activated following the autocatalytic excision of their
      inhibitory N-terminal prosegment. PCSK9 is unique since the mature enzyme
      exhibits a cleaved prosegment complexed with the catalytic subunit and has no
      protease activity towards other substrates. Similar to other convertases, we
      hypothesized that the in trans presence of the PCSK9 prosegment would interfere
      with PCSK9's activity on the LDLR. Since the prosegment cannot be secreted alone,
      we engineered a chimeric protein using the Fc-region of human IgG1 fused to the
      PCSK9 prosegment. The expression of such Fcpro-fusion protein in HEK293 and HepG2
      cells resulted in a secreted protein that binds PCSK9 and markedly inhibits its
      activity on the LDLR. This was observed by either intracellular co-expression of
      PCSK9 and Fcpro or by an extracellular in vitro co-incubation of Fcpro with
      PCSK9. Structure-function studies revealed that the inhibitory function of Fcpro
      does not require the acidic N-terminal stretch (residues 31-58) nor the C
      terminal Gln 152 of the prosegment. Fcpro likely interacts with the prosegment
      and/or catalytic subunit of the prosegment=PCSK9 complex thereby allosterically
      modulating its function. Our data suggest a novel strategic approach for the
      design and isolation of PCSK9 inhibitors. 

PMID- 23951291
TI  - 670nm photobiomodulation as a novel protection against retinopathy of
      prematurity: evidence from oxygen induced retinopathy models.
AB  - INTRODUCTION: To investigate the validity of using 670nm red light as a
      preventative treatment for Retinopathy of Prematurity in two animal models of
      oxygen-induced retinopathy (OIR). MATERIALS AND METHODS: During and post exposure
      to hyperoxia, C57BL/6J mice or Sprague-Dawley rats were exposed to 670 nm light
      for 3 minutes a day (9J/cm2). Whole mounted retinas were investigated for
      evidence of vascular abnormalities, while sections of neural retina were used to
      quantify levels of cell death using the TUNEL technique. Organs were removed,
      weighed and independent histopathology examination performed. RESULTS: 670 nm
      light reduced neovascularisation, vaso-obliteration and abnormal peripheral
      branching patterns of retinal vessels in OIR. The neural retina was also
      protected against OIR by 670 nm light exposure. OIR-exposed animals had severe
      lung pathology, including haemorrhage and oedema, that was significantly reduced
      in 670 nm+OIR light-exposed animals. There were no significance differences in
      the organ weights of animals in the 670 nm light-exposed animals, and no adverse
      effects of exposure to 670 nm light were detected. DISCUSSION: Low levels of
      exposure to 670 nm light protects against OIR and lung damage associated with
      exposure to high levels of oxygen, and may prove to be a non-invasive and
      inexpensive preventative treatment for ROP and chronic lung disease associated
      with prematurity.

PMID- 23951292
TI  - AcmD, a homolog of the major autolysin AcmA of Lactococcus lactis, binds to the
      cell wall and contributes to cell separation and autolysis.
AB  - Lactococcus lactis expresses the homologous glucosaminidases AcmB, AcmC, AcmA and
      AcmD. The latter two have three C-terminal LysM repeats for peptidoglycan
      binding. AcmD has much shorter intervening sequences separating the LysM repeats
      and a lower iso-electric point (4.3) than AcmA (10.3). Under standard laboratory
      conditions AcmD was mainly secreted into the culture supernatant. An L. lactis
      acmAacmD double mutant formed longer chains than the acmA single mutant,
      indicating that AcmD contributes to cell separation. This phenotype could be
      complemented by plasmid-encoded expression of AcmD in the double mutant. No clear
      difference in cellular lysis and protein secretion was observed between both
      mutants. Nevertheless, overexpression of AcmD resulted in increased autolysis
      when AcmA was present (as in the wild type strain) or when AcmA was added to the
      culture medium of an AcmA-minus strain. Possibly, AcmD is mainly active within
      the cell wall, at places where proper conditions are present for its binding and
      catalytic activity. Various fusion proteins carrying either the three LysM
      repeats of AcmA or AcmD were used to study and compare their cell wall binding
      characteristics. Whereas binding of the LysM domain of AcmA took place at pHs
      ranging from 4 to 8, LysM domain of AcmD seems to bind strongest at pH 4. 

PMID- 23951293
TI  - Persistent overexpression of phosphoglycerate mutase, a glycolytic enzyme,
      modifies energy metabolism and reduces stress resistance of heart in mice.
AB  - BACKGROUND: Heart failure is associated with changes in cardiac energy
      metabolism. Glucose metabolism in particular is thought to be important in the
      pathogenesis of heart failure. We examined the effects of persistent
      overexpression of phosphoglycerate mutase 2 (Pgam2), a glycolytic enzyme, on
      cardiac energy metabolism and function. METHODS AND RESULTS: Transgenic mice
      constitutively overexpressing Pgam2 in a heart-specific manner were generated,
      and cardiac energy metabolism and function were analyzed. Cardiac function at
      rest was normal. The uptake of analogs of glucose or fatty acids and the
      phosphocreatine/betaATP ratio at rest were normal. A comprehensive metabolomic
      analysis revealed an increase in the levels of a few metabolites immediately
      upstream and downstream of Pgam2 in the glycolytic pathway, whereas the levels of
      metabolites in the initial few steps of glycolysis and lactate remained
      unchanged. The levels of metabolites in the tricarboxylic acid (TCA) cycle were
      altered. The capacity for respiration by isolated mitochondria in vitro was
      decreased, and that for the generation of reactive oxygen species (ROS) in vitro
      was increased. Impaired cardiac function was observed in response to dobutamine.
      Mice developed systolic dysfunction upon pressure overload. CONCLUSIONS:
      Constitutive overexpression of Pgam2 modified energy metabolism and reduced
      stress resistance of heart in mice.

PMID- 23951294
TI  - Scaling up antiretroviral treatment services in Karnataka, India: impact on CD4
      counts of HIV-infected people.
AB  - SETTING: Twelve antiretroviral treatment centres under National AIDS Control
      Programme (NACP), Karnataka State, India. OBJECTIVE: For the period 2004-2011, to
      describe the trends in the numbers of people living with HIV (PLHIV) registered
      for care and their median baseline CD4 counts, disaggregated by age and sex.
      DESIGN: Descriptive study involving analysis of routinely captured data (year of
      registration, age, sex, baseline CD4 count) under NACP. RESULTS: 34,882 (97% of
      total eligible) PLHIV were included in analysis. The number registered for care
      has increased by over 12 times during 2004-11; with increasing numbers among
      females. The median baseline CD4 cell count rose from 125 in 2004 to 235 in 2011-
      the increase was greater among females as compared to males. However, about two
      thirds still presented at CD4 cell counts less than 350. CONCLUSION: We found an
      increasing trend of median CD4 counts among PLHIV presenting to ART centres in
      Karnataka, an indicator of enhanced and early access to HIV care. Equal
      proportion of females and higher baseline CD4 counts among them allays any fear
      of differential access by gender. Despite this relative success, a substantial
      proportion still presented at low CD4 cell counts indicating possibly delayed HIV
      diagnosis and delayed linkage to HIV care. Universal HIV testing at health care
      facilities and strengthening early access to care are required to bridge the gap.

PMID- 23951295
TI  - Measuring visual field progression in the central 10 degrees using additional
      information from central 24 degrees visual fields and 'lasso regression'.
AB  - PURPOSE: To measure progression of the visual field (VF) mean deviation (MD)
      index in longitudinal 10-2 VFs more accurately, by adding information from 24-2
      VFs using Lasso regression. METHODS: A training dataset consisted of 138 eyes
      from 97 patients with glaucoma or ocular hypertension and a testing dataset
      consisted of 40 eyes from 34 patients with glaucoma or ocular hypertension. The
      Lasso method was used to predict total deviation (TD) values in training
      patients' 10-2 VFs based on information from their 24-2 VFs (52 TD values, foveal
      sensitivity and mean deviation MD). Then, the MD of each patient's 10-2 VF was
      estimated as the average of these Lasso-predicted TD values (10-2 VF 'Lasso MD';
      LMD). Finally, linear regression was applied to each testing patient's series of
      longitudinal 10-2 VF MDs with and without additional Lasso-derived LMDs in order
      to predict future MDs not included in the regression analysis. Absolute
      prediction errors were compared when only actual 10-2 MDs were regressed against
      when a combination of actual 10-2 MDs and LMDs were regressed. RESULTS: THE
      AVERAGE ABSOLUTE PREDICTION ERROR WAS SIGNIFICANTLY SMALLER FOR THE NOVEL METHOD
      INCORPORATING LMDS (RANGE: 1.6 to 1.8 dB) compared with the standard approach
      (range: 1.7 to 3.4 dB) (p<0.05, ANOVA test). CONCLUSIONS: Deriving 10-2 VF MD
      values from 24-2 VFs improves the prediction accuracy of progression. This
      approach will help clinicians to predict patients' visual function in the
      parafoveal area.

PMID- 23951296
TI  - A network extension of species occupancy models in a patchy environment applied
      to the Yosemite Toad (Anaxyrus canorus).
AB  - A central challenge of conservation biology is using limited data to predict rare
      species occurrence and identify conservation areas that play a disproportionate
      role in regional persistence. Where species occupy discrete patches in a
      landscape, such predictions require data about environmental quality of
      individual patches and the connectivity among high quality patches. We present a
      novel extension to species occupancy modeling that blends traditional predictions
      of individual patch environmental quality with network analysis to estimate
      connectivity characteristics using limited survey data. We demonstrate this
      approach using environmental and geospatial attributes to predict observed
      occupancy patterns of the Yosemite toad (Anaxyrus (= Bufo) canorus) across >2,500
      meadows in Yosemite National Park (USA). A. canorus, a Federal Proposed Species,
      breeds in shallow water associated with meadows. Our generalized linear model
      (GLM) accurately predicted ~84% of true presence-absence data on a subset of data
      withheld for testing. The predicted environmental quality of each meadow was
      iteratively 'boosted' by the quality of neighbors within dispersal distance. We
      used this park-wide meadow connectivity network to estimate the relative
      influence of an individual Meadow's 'environmental quality' versus its 'network
      quality' to predict: a) clusters of high quality breeding meadows potentially
      linked by dispersal, b) breeding meadows with high environmental quality that are
      isolated from other such meadows, c) breeding meadows with lower environmental
      quality where long-term persistence may critically depend on the network
      neighborhood, and d) breeding meadows with the biggest impact on park-wide
      breeding patterns. Combined with targeted data on dispersal, genetics, disease,
      and other potential stressors, these results can guide designation of core
      conservation areas for A. canorus in Yosemite National Park. 

PMID- 23951297
TI  - Antifungal activity of phlorotannins against dermatophytes and yeasts: approaches
      to the mechanism of action and influence on Candida albicans virulence factor.
AB  - In the last few decades, fungal infections, particularly nosocomial, increased
      all around the world. This increment stimulated the search for new antifungal
      agents, especially those derived from nature. Among natural products, those from
      marine sources have gained prominence in the last years. Purified phlorotannins
      extracts from three brown seaweeds (Cystoseira nodicaulis (Withering) M. Roberts,
      Cystoseira usneoides (Linnaeus) M. Roberts and Fucus spiralis Linnaeus) were
      screened for their antifungal activity against human pathogenic yeast and
      filamentous fungi. The purified phlorotannins extracts from the studied seaweeds
      displayed fungistatic and fungicidal activity against yeast and dermatophytes,
      respectively, pointing to their interest as anti-dermatophyte agent. C. albicans
      ATCC 10231 was the most susceptible among yeast, while Epidermophyton floccosum
      and Trichophyton rubrum were the most susceptible among dermatophytes. Since the
      antifungal mechanism constitutes an important strategy for limiting the emergence
      of resistance to the commercially available agents, the mechanism of action of
      purified phlorotannins extracts was approached. C. nodicaulis and C. usneoides
      seem to act by affecting the ergosterol composition of the cell membrane of yeast
      and dermatophyte, respectively. F. spiralis influenced the dermatophyte cell wall
      composition by reducing the levels of chitin. Phlorotannins also seem to affect
      the respiratory chain function, as all of the studied species significantly
      increased the activity of mitochondrial dehydrogenases and increased the
      incorporation of rhodamine 123 by yeast cells. Phlorotannins from F. spiralis
      inhibited the dimorphic transition of Candida albicans, leading to the formation
      of pseudohyphae with diminished capacity to adhere to epithelial cells. This
      finding is associated with a decrease of C. albicans virulence and capacity to
      invade host cells and can be potentially interesting for combined antifungal
      therapy, namely for the control of invasive candidiasis. 

PMID- 23951298
TI  - Prognostic significance of ESR1 amplification and ESR1 PvuII, CYP2C19*2,
      UGT2B15*2 polymorphisms in breast cancer patients.
AB  - INTRODUCTION: Amplification of the ESR1 gene, coding for estrogen receptor alpha,
      was shown to predict responsiveness to tamoxifen, however its prognostic impact
      in breast cancer patients has not been thoroughly investigated. Other factors
      that could contribute to responsiveness to tamoxifen treatment are polymorphisms
      in ESR1 gene and genes involved in tamoxifen metabolism. The aim of this study
      was to assess the prognostic role of ESR1 gene dosage in a consecutive group of
      breast cancer patients and to correlate this feature with clinico-pathological
      factors. Additionally, ESR1 PvuII, CYP2C19*2 and UGT2B15*2 polymorphisms were
      analyzed in the tamoxifen-treated subgroup of patients. MATERIALS AND METHODS:
      Primary tumor samples from 281 stage I-III consecutive breast cancer patients
      were analyzed for ESR1 gene dosage using real-time PCR with locked nucleic acids
      hydrolysis probes. In the tamoxifen-treated subgroup of patients, ESR1 PvuII,
      CYP2C19*2 and UGT2B15*2 polymorphism in leukocytes genomic DNA were analyzed.
      Results were correlated with clinico-pathological factors and with disease-free
      survival (DFS) and overall survival (OS). RESULTS: ESR1 amplification (with a cut
      off level of 2.0) was found in 12% of the entire group of breast cancer patients,
      and in 18% of the ER-negative subgroup. This feature was associated with
      decreased DFS both in the entire group (P=0.007) and in the ER-negative subgroup
      (P=0.03), but not in the tamoxifen-treated patients. Patients with ESR1 PvuII
      wt/wt genotype and at least one UGT2B15 wt allele had a worse DFS (P=0.03) and
      showed a trend towards decreased Os (P=0.08) in comparison to patients with ESR1
      PvuII wt/vt or vt/vt genotype and UGT2B15 *2/*2 genotype. CONCLUSIONS: ESR1
      amplification can occur in ER-negative tumors and may carry poor prognosis. In
      the tamoxifen-treated subgroup, poor prognosis was related to the combined
      presence of ESR1 PvuII wt/wt and UGT2B15wt/wt or wt/*2 genotype.

PMID- 23951299
TI  - Identification of episomal human papillomavirus and other DNA viruses in
      cytological anal samples of HIV-uninfected men who have sex with men.
AB  - To date, there have been only few studies that investigated integration of anal
      Human Papillomavirus (HPV). Most of them were conducted on HIV-infected
      individuals and mainly analyzed samples from high-grade lesions and invasive
      cancer. We aimed to investigate HPV physical status in HIV-negative men who have
      sex with men (MSM) with a detectable anal HPV infection, irrespective of the
      presence of lesions. We also sought to explore the presence of other circular DNA
      viruses in the anal region. Study participants were attendees of an STI screening
      program, which were also screened for anal HPV infection and cytological
      abnormalities. HPV physical status was assessed using multiply-primed RCA. HPV16
      positive samples were also analyzed using E2/E6 multiplex PCR, qRT-PCR and APOT
      assay. RCA and virus-specific PCR were employed to investigate the presence of
      other DNA viruses. Anal HPV infection was detected in 76.9% of the 230 MSM
      enrolled. The anal cytological reports were: 129 NILM, 37 ASC-US and 28 L-SIL (36
      samples were inadequate for interpretation). HPV physical status was evaluated in
      the 109 anal specimens that harbored one or two different HPV genotypes.
      Integration was observed only in one HPV16-positive sample (0.9%), in which
      integrate-derived viral transcripts of type B were detected. Integration occurred
      in chromosome 14 q. In 22 of the 53 (41.5%) mucosal HPV-negative samples, RCA
      restriction results would seem to indicate the presence of circular DNA viruses.
      Indeed, cutaneous HPV (4 samples), MCPyV (5 samples) and TTV (4 samples) were
      detected. In conclusion, anal HPV integration was rarely evidenced in HIV
      uninfected MSM with no or mild anal cytological abnormalities, although the
      integration rate may have been underestimated because of the limitations of the
      employed assays. Other DNA viruses were detected in the anal samples of these
      individuals, although the significance of this occurrence needs to be assessed. 

PMID- 23951301
TI  - Sex-specific heritability of spontaneous lipid levels in an extended pedigree of
      Indian-origin rhesus macaques (Macaca mulatta).
AB  - The rhesus macaque is an important model for human atherosclerosis but genetic
      determinants of relevant phenotypes have not yet been investigated in this
      species. Because lipid levels are well-established and heritable risk factors for
      human atherosclerosis, our goal was to assess the heritability of lipoprotein
      cholesterol and triglyceride levels in a single, extended pedigree of 1,289
      Indian-origin rhesus macaques. Additionally, because increasing evidence supports
      sex differences in the genetic architecture of lipid levels and lipid metabolism
      in humans and macaques, we also explored sex-specific heritability for all lipid
      measures investigated in this study. Using standard methods, we measured
      lipoprotein cholesterol and triglyceride levels from fasted plasma in a sample of
      193 pedigreed rhesus macaques selected for membership in large, paternal half-sib
      cohorts, and maintained on a low-fat, low cholesterol chow diet. Employing a
      variance components approach, we found moderate heritability for total
      cholesterol (h2=0.257, P=0.032), LDL cholesterol (h2=0.252, P=0.030), and
      triglyceride levels (h2=0.197, P=0.034) in the full sample. However,
      stratification by sex (N=68 males, N=125 females) revealed substantial sex
      specific heritability for total cholesterol (0.644, P=0.004, females only), HDL
      cholesterol (0.843, P=0.0008, females only), VLDL cholesterol (0.482, P=0.018,
      males only), and triglyceride levels (0.705, P=0.001, males only) that was
      obscured or absent when sexes were combined in the full sample. We conclude that
      genes contribute to spontaneous variation in circulating lipid levels in the
      Indian-origin rhesus macaque in a sex-specific manner, and that the rhesus
      macaque is likely to be a valuable model for sex-specific genetic effects on
      lipid risk factors for human atherosclerosis. These findings are a first-ever
      report of heritability for cholesterol levels in this species, and support the
      need for expanded analysis of these traits in this population.

PMID- 23951300
TI  - Dynamic contrast-enhanced MR imaging predicts local control in oropharyngeal or
      hypopharyngeal squamous cell carcinoma treated with chemoradiotherapy.
AB  - The role of pretreatment dynamic contrast-enhanced perfusion MR imaging (DCE-PWI)
      and diffusion-weighted MR imaging (DWI) in predicting the treatment response of
      oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) to chemoradiation
      remains unclear. We prospectively investigated the ability of pharmacokinetic
      parameters derived from pretreatment DCE-PWI and DWI to predict the local control
      of OHSCC patients treated with chemoradiation. Between August, 2010 and March,
      2012, patients with untreated OHSCC scheduled for chemoradiation were eligible
      for this prospective study. DCE-PWI and DWI were performed in addition to
      conventional MRI. The relationship of local control with the following clinical
      and imaging variables was analyzed: the hemoglobin level, T-stage, tumor
      location, gross tumor volume, maximum standardized uptake value, metabolic tumor
      volume and total lesion glycolysis on FDG PET/CT, transfer constant (K (trans) ),
      volume of blood plasma and volume of extracellular extravascular space on DCE
      PWI, and apparent diffusion coefficient on DWI of the primary tumor. The patients
      were also divided into a local control group and a local failure group, and their
      clinical and imaging parameters were compared. There were 58 patients (29 with
      oropharynx squamous cell carcinoma [SCC] and 29 with hypopharynx SCC) with
      successful pretreatment DCE-PWI and DWI available for analysis. After a median
      follow-up of 18.2 months, 17 (29.3%) participants had local failure, whereas the
      remaining 41 patients achieved local control. Univariate analysis revealed that
      only the K (trans) value was significantly associated with local control (P =
      0.03). When the local control and local failure groups were compared, significant
      differences were observed in K (trans) and the tumor location (P = 0.01 and P =
      0.04, respectively). In the multivariable analysis, only K (trans) was
      statistically significant (P = 0.04). Our results suggest that pretreatment K
      (trans) may help predict the local control in OHSCC patients treated with
      chemoradiation. 

PMID- 23951302
TI  - A comprehensive quantitative assessment of bird extinction risk in Brazil.
AB  - In an effort to avoid species loss, scientists have focused their efforts on the
      mechanisms making some species more prone to extinction than others. However,
      species show different responses to threats given their evolutionary history,
      behavior, and intrinsic biological features. We used bird biological features and
      external threats to (1) understand the multiple pathways driving Brazilian bird
      species to extinction, (2) to investigate if and how extinction risk is
      geographically structured, and (3) to quantify how much diversity is currently
      represented inside protected areas. We modeled the extinction risk of 1557 birds
      using classification trees and evaluated the relative contribution of each
      biological feature and external threat in predicting extinction risk. We also
      quantified the proportion of species and their geographic range currently
      protected by the network of Brazilian protected areas. The optimal classification
      tree showed different pathways to bird extinction. Habitat conversion was the
      most important predictor driving extinction risk though other variables, such as
      geographic range size, type of habitat, hunting or trapping and trophic guild,
      were also relevant in our models. Species under higher extinction risk were
      concentrated mainly in the Cerrado Biodiversity Hotspot and were not quite
      represented inside protected areas, neither in richness nor range. Predictive
      models could assist conservation actions, and this study could contribute by
      highlighting the importance of natural history and ecology in these actions. 

PMID- 23951303
TI  - A LacI-family regulator activates maltodextrin metabolism of Enterococcus
      faecium.
AB  - Enterococcus faecium is a gut commensal of humans and animals. In the intestinal
      tract, E. faecium will have access to a wide variety of carbohydrates, including
      maltodextrins and maltose, which are the sugars that result from the enzymatic
      digestion of starch by host-derived and microbial amylases. In this study, we
      identified the genetic determinants for maltodextrin utilization of E. faecium
      E1162. We generated a deletion mutant of the mdxABCD-pulA gene cluster that is
      homologous to maltodextrin uptake genes in other Gram-positive bacteria, and a
      deletion mutant of the mdxR gene, which is predicted to encode a LacI family
      regulator of mdxABCD-pulA. Both mutations impaired growth on maltodextrins but
      had no effect on the growth on maltose and glucose. Comparative transcriptome
      analysis showed that eight genes (including mdxABCD-pulA) were expressed at
      significantly lower levels in the isogenic DeltamdxR mutant strain compared to
      the parental strain when grown on maltose. Quantitative real-time RT-PCR
      confirmed the results of transcriptome analysis and showed that the transcription
      of a putative maltose utilization gene cluster is induced in a semi-defined
      medium supplemented with maltose but is not regulated by MdxR. Understanding the
      maltodextrin metabolism of E. faecium could yield novel insights into the
      underlying mechanisms that contribute to the gut commensal lifestyle of E.
      faecium. 

PMID- 23951304
TI  - Interferon-gamma increases the ratio of matrix metalloproteinase-9/tissue
      inhibitor of metalloproteinase-1 in peripheral monocytes from patients with
      coronary artery disease.
AB  - Acute coronary syndromes (ACS) may be triggered by acute infections. Systemic
      production of interferon gamma (IFN-gamma) is induced during infection and
      regulates the production of matrix metalloproteinases (MMPs) and their inhibitors
      (TIMPs), both important in plaque stability. This study evaluates the effect of
      IFN-gamma on the MMPs/TIMP-1 ratio in cultured monocytes from 30 patients with
      stable coronary artery disease (CAD), 30 with unstable angina (UA) or non-ST
      segment elevation myocardial infarction (NSTEMI), and 30 healthy blood donors.
      Supernatant concentrations of MMP-1, -2, -9, and TIMP-1 were measured by enzyme
      linked immunoassays. Basal concentration of MMP-1 and TIMP-1 was similar between
      groups, while MMP-2 was higher in healthy individuals and MMP-9 in patients with
      UA/NSTEMI. Upon IFN-gamma stimulation, MMP-9 secretion increased in all groups,
      while TIMP-1 decreased only in patients with CAD, which in turn result in a
      strikingly elevation in their mean MMP-9/TIMP-1 ratio. MMP-1/TIMP-1 and MMP
      2/TIMP-1 ratios were <1.0 in basal conditions and after stimulation in all
      groups. Our results suggest that nonstimulated monocytes from patients with
      stable CAD show a similar behavior than those from healthy individuals. However,
      stimulation with IFN-gamma induces an increase on the MMP-9/TIMP-1 ratio as high
      as that found in patients with ACS. Thus, it may bring biological plausibility to
      the association between acute infections and the development of ACS. 

PMID- 23951305
TI  - Oxalic acid has an additional, detoxifying function in Sclerotinia sclerotiorum
      pathogenesis.
AB  - The mechanism of the diseases caused by the necrotroph plant pathogen Sclerotinia
      sclerotiorum is not well understood. To investigate the role of oxalic acid
      during infection high resolution, light-, scanning-, transmission electron
      microscopy and various histochemical staining methods were used. Our inoculation
      method allowed us to follow degradation of host plant tissue around single hyphae
      and to observe the reaction of host cells in direct contact with single invading
      hyphae. After penetration the outer epidermal cell wall matrix appeared degraded
      around subcuticular hyphae (12-24 hpi). Calcium oxalate crystals were detected in
      advanced (36-48 hpi) and late (72 hpi) infection stages, but not in early stages.
      In early infection stages, surprisingly, no toxic effect of oxalic acid
      eventually secreted by S. sclerotiorum was observed. As oxalic acid is a common
      metabolite in plants, we propose that attacked host cells are able to metabolize
      oxalic acid in the early infection stage and translocate it to their vacuoles
      where it is stored as calcium oxalate. The effects, observed on healthy tissue
      upon external application of oxalic acid to non-infected, living tissue and cell
      wall degradation of dead host cells starting at the inner side of the walls
      support this idea. The results indicate that oxalic acid concentrations in the
      early stage of infection stay below the toxic level. In plant and fungi oxalic
      acid/calcium oxalate plays an important role in calcium regulation. Oxalic acid
      likely could quench calcium ions released during cell wall breakdown to protect
      growing hyphae from toxic calcium concentrations in the infection area. As
      calcium antimonate-precipitates were found in vesicles of young hyphae, we
      propose that calcium is translocated to the older parts of hyphae and detoxified
      by building non-toxic, stable oxalate crystals. We propose an infection model
      where oxalic acid plays a detoxifying role in late infection stages. 

PMID- 23951306
TI  - Beta-amyloid impairs reelin signaling.
AB  - Reelin is a signaling protein increasingly associated with the pathogenesis of
      Alzheimer's disease that relevantly modulates tau phosphorylation. We have
      previously demonstrated that beta-amyloid peptide (Abeta) alters reelin
      expression. We have now attempted to determine whether abnormal reelin triggered
      by Abeta will result in signaling malfunction, contributing to the pathogenic
      process. Here, we show that reelin forms induced by beta-amyloid are less capable
      of down-regulating tau phosphorylation via disabled-1 and GSK3beta kinase. We
      also demonstrate that the scaffold protein 14-3-3 that increases tau
      phosphorylation by modulating GSK3beta activity, is up-regulated during defective
      reelin signaling. Binding of reelin to its receptor, mainly ApoER2 in the brain,
      relays the signal into the cell. We associate the impaired reelin signaling with
      inefficiency of reelin in forming active homodimers and decreased ability to bind
      efficiently to its receptor, ApoER2. More remarkably, reelin from Alzheimer
      cortex shows a tendency to form large complexes instead of homodimers, the active
      form for signaling. Our results suggest that reelin expression is altered by
      Abeta leading to impaired reelin signaling. 

PMID- 23951307
TI  - Illicit drug use is a significant risk factor for loss to follow up in patients
      with HIV-1 infection at a large urban HIV clinic in Tokyo.
AB  - BACKGROUND: Loss to follow up (LTFU) is an important prognostic factor in
      patients with HIV-1 infection. The impact of illicit drug use on LTFU of patients
      with HIV-1 infection is unknown in Japan. METHODS: A single center observational
      study was conducted to elucidate the impact of illicit drug use on LTFU at a
      large HIV clinic in Tokyo. LTFU was defined as those who discontinued their
      visits to the clinic for at least 12 months and were not known to be under the
      care of other facilities or have died within 12 months of their last visit.
      Patients who first visited the clinic between January 2005 and August 2010 were
      enrolled. Information on illicit drug use was collected in a structured interview
      and medical charts. Comparison of the effects of illicit drug use and no use on
      LTFU was conducted by uni- and multi-variate Cox hazards models as the primary
      exposure. RESULTS: The study subjects were 1,208 patients, mostly Japanese men,
      of relatively young age, and infected through homosexual contact. A total of 111
      patients (9.2%) were LTFU (incidence: 24.9 per 1,000 person-years). Among illicit
      drug users and non users, 55 (13.3%) and 56 (7.1%) patients, respectively, were
      LTFU, with incidence of 35.7 and 19.2 per 1,000 person-years, respectively. Uni-
      and multi-variate analyses showed that illicit drug use was a significant risk
      for LTFU (HR=1.860; 95% CI, 1.282-2.699; p=0.001) (adjusted HR=1.544; 95% CI,
      1.028-2.318; p=0.036). Multivariate analysis also identified young age, high CD4
      count, no antiretroviral therapy, and no health insurance as risk factors for
      LTFU. CONCLUSIONS: The incidence of LTFU among illicit drug users was almost
      twice higher than that among non users. Effective intervention for illicit drug
      use in this population is warranted to ensure proper treatment and prevent the
      spread of HIV.

PMID- 23951308
TI  - The g0/g1 switch gene 2 is an important regulator of hepatic triglyceride
      metabolism.
AB  - Nonalcoholic fatty liver disease is associated with obesity and insulin
      resistance. Factors that regulate the disposal of hepatic triglycerides
      contribute to the development of hepatic steatosis. G0/G1 switch gene 2 (G0S2) is
      a target of peroxisome proliferator-activated receptors and plays an important
      role in regulating lipolysis in adipocytes. Therefore, we investigated whether
      G0S2 plays a role in hepatic lipid metabolism. Adenovirus-mediated expression of
      G0S2 (Ad-G0S2) potently induced fatty liver in mice. The liver mass of Ad-G0S2
      infected mice was markedly increased with excess triglyceride content compared to
      the control mice. G0S2 did not change cellular cholesterol levels in hepatocytes.
      G0S2 was found to be co-localized with adipose triglyceride lipase at the surface
      of lipid droplets. Hepatic G0S2 overexpression resulted in an increase in plasma
      Low-density lipoprotein (LDL)/Very-Low-density (VLDL) lipoprotein cholesterol
      level. Plasma High-density lipoprotein (HDL) cholesterol and ketone body levels
      were slightly decreased in Ad-G0S2 injected mice. G0S2 also increased the
      accumulation of neutral lipids in cultured HepG2 and L02 cells. However, G0S2
      overexpression in the liver significantly improved glucose tolerance in mice.
      Livers expressing G0S2 exhibited increased 6-(N-(7-nitrobenz-2-oxa-1-3-diazol-4
      yl) amino)-6-deoxyglucose uptake compared with livers transfected with control
      adenovirus. Taken together, our results provide evidence supporting an important
      role for G0S2 as a regulator of triglyceride content in the liver and suggest
      that G0S2 may be a molecular target for the treatment of insulin resistance and
      other obesity-related metabolic disorders. 

PMID- 23951309
TI  - Differences in mucosal gene expression in the colon of two inbred mouse strains
      after colonization with commensal gut bacteria.
AB  - The host genotype has been proposed to contribute to individually composed
      bacterial communities in the gut. To provide deeper insight into interactions
      between gut bacteria and host, we associated germ-free C3H and C57BL/10 mice with
      intestinal bacteria from a C57BL/10 donor mouse. Analysis of microbiota
      similarity between the animals with denaturing gradient gel electrophoresis
      revealed the development of a mouse strain-specific microbiota. Microarray-based
      gene expression analysis in the colonic mucosa identified 202 genes whose
      expression differed significantly by a factor of more than 2. Application of
      bioinformatics tools demonstrated that functional terms including
      signaling/secretion, lipid degradation/catabolism, guanine nucleotide/guanylate
      binding and immune response were significantly enriched in differentially
      expressed genes. We had a closer look at the 56 genes with expression differences
      of more than 4 and observed a higher expression in C57BL/10 mice of the genes
      coding for Tlr1 and Ang4 which are involved in the recognition and response to
      gut bacteria. A higher expression of Pla2g2a was detected in C3H mice. In
      addition, a number of interferon-inducible genes were higher expressed in C3H
      than in C57BL/10 mice including Gbp1, Mal, Oasl2, Ifi202b, Rtp4, Ly6g6c,
      Ifi27l2a, Usp18, Ifit1, Ifi44, and Ly6g indicating that interferons may play an
      essential role in microbiota regulation. However, genes coding for interferons,
      their receptors, factors involved in interferon expression regulation or
      signaling pathways were not differentially expressed between the two mouse
      strains. Taken together, our study confirms that the host genotype is involved in
      the establishment of host-specific bacterial communities in the gut. Based on
      expression differences after colonization with the same bacterial inoculum, we
      propose that Pla2g2a and interferon-dependent genes may contribute to this
      phenomenon. 

PMID- 23951310
TI  - CCL18 exhibits a regulatory role through inhibition of receptor and
      glycosaminoglycan binding.
AB  - CCL18 has been reported to be present constitutively at high levels in the
      circulation, and is further elevated during inflammatory diseases. Since it is a
      rather poor chemoattractant, we wondered if it may have a regulatory role. CCL18
      has been reported to inhibit cellular recruitment mediated by CCR3, and we have
      shown that whilst it is a competitive functional antagonist as assessed by Schild
      plot analysis, it only binds to a subset of CCR3 receptor populations. We have
      extended this inhibitory activity to other receptors and have shown that CCL18 is
      able to inhibit CCR1, CCR2, CCR4 and CCR5 mediated chemotaxis, but has no effect
      on CCR7 and CCR9, nor the CXC receptors that we have tested. Whilst CCL18 is able
      to bind to CCR3, it does not bind to the other receptors that it inhibits. We
      therefore tested the hypothesis that it may displace glycosaminoglycan (GAG)
      chemokines bound either in cis- on the leukocyte, or in trans-presentation on the
      endothelial surface, thereby inhibiting the recruitment of leukocytes into the
      site of inflammation. We show that CCL18 selectivity displaces heparin bound
      chemokines, and that chemokines from all four chemokine sub-classes displace cell
      bound CCL18. We propose that CCL18 has regulatory properties inhibiting chemokine
      function when GAG-mediated presentation plays a role in receptor activation. 

PMID- 23951311
TI  - A novel application of furazolidone: anti-leukemic activity in acute myeloid
      leukemia.
AB  - Acute myeloid leukemia (AML) is the most common malignant myeloid disorder of
      progenitor cells in myeloid hematopoiesis and exemplifies a genetically
      heterogeneous disease. The patients with AML also show a heterogeneous response
      to therapy. Although all-trans retinoic acid (ATRA) has been successfully
      introduced to treat acute promyelocytic leukemia (APL), it is rather ineffective
      in non-APL AML. In our present study, 1200 off-patent marketed drugs and natural
      compounds that have been approved by the Food and Drug Administration (FDA) were
      screened for anti-leukemia activity using the retrovirus
      transduction/transformation assay (RTTA). Furazolidone (FZD) was shown to inhibit
      bone marrow transformation mediated by several leukemia fusion proteins,
      including AML1-ETO. Furazolidone has been used in the treatment of certain
      bacterial and protozoan infections in human and animals for more than sixty
      years. We investigated the anti-leukemic activity of FZD in a series of AML
      cells. FZD displayed potent antiproliferative properties at submicromolar
      concentrations and induced apoptosis in AML cell lines. Importantly, FZD
      treatment of certain AML cells induced myeloid cell differentiation by morphology
      and flow cytometry for CD11b expression. Furthermore, FZD treatment resulted in
      increased stability of tumor suppressor p53 protein in AML cells. Our in vitro
      results suggest furazolidone as a novel therapeutic strategy in AML patients. 

PMID- 23951312
TI  - Free-living turtles are a reservoir for Salmonella but not for Campylobacter.
AB  - Different studies have reported the prevalence of Salmonella in turtles and its
      role in reptile-associated salmonellosis in humans, but there is a lack of
      scientific literature related with the epidemiology of Campylobacter in turtles.
      The aim of this study was to evaluate the prevalence of Campylobacter and
      Salmonella in free-living native (Emys orbicularis, n=83) and exotic
      (Trachemysscripta elegans, n=117) turtles from 11 natural ponds in Eastern Spain.
      In addition, different types of samples (cloacal swabs, intestinal content and
      water from Turtle containers) were compared. Regardless of the turtle species,
      natural ponds where individuals were captured and the type of sample taken,
      Campylobacter was not detected. Salmonella was isolated in similar proportions in
      native (8.0 +/- 3.1%) and exotic (15.0 +/- 3.3%) turtles (p=0.189). The
      prevalence of Salmonella positive turtles was associated with the natural ponds
      where animals were captured. Captured turtles from 8 of the 11 natural ponds were
      positive, ranged between 3.0 +/- 3.1% and 60.0 +/- 11.0%. Serotyping revealed 8
      different serovars among four Salmonella enterica subspecies: S. enterica subsp.
      enterica (n = 21), S. enterica subsp. salamae (n = 2), S. enterica subsp.
      diarizonae (n = 3), and S. enterica subsp. houtenae (n = 1). Two serovars were
      predominant: S. Thompson (n=16) and S. typhimurium (n=3). In addition, there was
      an effect of sample type on Salmonella detection. The highest isolation of
      Salmonella was obtained from intestinal content samples (12.0 +/- 3.0%), while
      lower percentages were found for water from the containers and cloacal swabs (8.0
      +/- 2.5% and 3.0 +/- 1.5%, respectively). Our results imply that free-living
      turtles are a risk factor for Salmonella transmission, but do not seem to be a
      reservoir for Campylobacter. We therefore rule out turtles as a risk factor for
      human campylobacteriosis. Nevertheless, further studies should be undertaken in
      other countries to confirm these results.

PMID- 23951313
TI  - Mitochondrial transcription factor A, an endogenous danger signal, promotes
      TNFalpha release via RAGE- and TLR9-responsive plasmacytoid dendritic cells.
AB  - OBJECTIVE: Mitochondrial transcription factor A (TFAM) is normally bound to and
      remains associated with mitochondrial DNA (mtDNA) when released from damaged
      cells. We hypothesized that TFAM, bound to mtDNA (or equivalent CpG-enriched
      DNA), amplifies TNFalpha release from TLR9-expressing plasmacytoid dendritic
      cells (pDCs) by engaging RAGE. MATERIALS AND METHODS: Murine Flt3 ligand-expanded
      splenocytes obtained from C57BL/6 mice were treated with recombinant human TFAM,
      alone or in combination with CpG-enriched DNA with subsequent TNFalpha release
      measured by ELISA. The role of RAGE was determined by pre-treatment with soluble
      RAGE or heparin or by employing matching RAGE (-/-) splenocytes. TLR9 signaling
      was evaluated using a specific TLR9-blocking oligonucleotide and by inhibiting
      endosomal processing, PI3K and NF-kappaB. Additional studies examined whether
      heparin sulfate moieties or endothelin converting enzyme-1 (ECE-1)-dependent
      recycling of endosomal receptors were required for TFAM and CpG DNA recognition.
      MAIN RESULTS: TFAM augmented splenocyte TNFalpha release in response to CpGA DNA,
      which was strongly dependent upon pDCs and regulated by RAGE and TLR9 receptors.
      Putative TLR9 signaling pathways, including endosomal acidification and signaling
      through PI3K and NF-kappaB, were essential for splenocyte TNFalpha release in
      response to TFAM+CpGA DNA. Interestingly, TNFalpha release depended upon
      endothelin converting enzyme (ECE)-1, which cleaves and presumably activates TLR9
      within endosomes. Recognition of the TFAM-CpGA DNA complex was dependent upon
      heparin sulfate moieties, and recombinant TFAM Box 1 and Box 2 proteins were
      equivalent in terms of augmenting TNFalpha release. CONCLUSIONS: TFAM promoted
      TNFalpha release in a splenocyte culture model representing complex cell-cell
      interactions in vivo with pDCs playing a critical role. To our knowledge, this
      study is the first to incriminate ECE-1-dependent endosomal cleavage of TLR9 as a
      critical step in the signaling pathway leading to TNFalpha release. These
      findings, and others reported herein, significantly advance our understanding of
      sterile immune responses triggered by mitochondrial danger signals.

PMID- 23951314
TI  - Cold adaptation, ca2+ dependency and autolytic stability are related features in
      a highly active cold-adapted trypsin resistant to autoproteolysis engineered for
      biotechnological applications.
AB  - Pig trypsin is routinely used as a biotechnological tool, due to its high
      specificity and ability to be stored as an inactive stable zymogen. However, it
      is not an optimum enzyme for conditions found in wound debriding for medical uses
      and trypsinization processes for protein analysis and animal cell culturing,
      where low Ca(2+) dependency, high activity in mild conditions and easy
      inactivation are crucial. We isolated and thermodynamically characterized a
      highly active cold-adapted trypsin for medical and laboratory use that is four
      times more active than pig trypsin at 10( degrees ) C and at least 50% more
      active than pig trypsin up to 50( degrees ) C. Contrary to pig trypsin, this
      enzyme has a broad optimum pH between 7 and 10 and is very insensitive to Ca(2+)
      concentration. The enzyme is only distantly related to previously described
      cryophilic trypsins. We built and studied molecular structure models of this
      trypsin and performed molecular dynamic calculations. Key residues and structures
      associated with calcium dependency and cryophilicity were identified. Experiments
      indicated that the protein is unstable and susceptible to autoproteolysis.
      Correlating experimental results and structural predictions, we designed
      mutations to improve the resistance to autoproteolysis and conserve activity for
      longer periods after activation. One single mutation provided around 25 times
      more proteolytic stability. Due to its cryophilic nature, this trypsin is easily
      inactivated by mild denaturation conditions, which is ideal for controlled
      proteolysis processes without requiring inhibitors or dilution. We clearly show
      that cold adaptation, Ca(2+) dependency and autolytic stability in trypsins are
      related phenomena that are linked to shared structural features and evolve in a
      concerted fashion. Hence, both structurally and evolutionarily they cannot be
      interpreted and studied separately as previously done.

PMID- 23951315
TI  - The C-terminal amino acid of the MHC-I heavy chain is critical for binding to
      Derlin-1 in human cytomegalovirus US11-induced MHC-I degradation.
AB  - Derlin-1 plays a critical role in endoplasmic reticulum-associated protein
      degradation (ERAD) of a particular subset of proteins. Although it is generally
      accepted that Derlin-1 mediates the export of ERAD substrates from the ER to the
      cytosol, little is known about how Derlin-1 interacts with these substrates.
      Human cytomegalovirus (HCMV) US11 exploits Derlin-1-dependent ERAD to degrade
      major histocompatibility complex class I (MHC-I) molecules and evade immune
      surveillance. US11 requires the cytosolic tail of the MHC-I heavy chain to divert
      MHC-I molecules into the ERAD pathway for degradation; however, the underlying
      mechanisms remain unknown. Here, we show that the cytosolic tail of the MHC-I
      heavy chain, although not required for interaction with US11, is required for
      tight binding to Derlin-1 and thus for US11-induced dislocation of the MHC-I
      heavy chain to the cytosol for proteasomal degradation. Surprisingly, deletion of
      a single C-terminal amino acid from the cytosolic tail disrupted the interaction
      between MHC-I molecules and Derlin-1, rendering mutant MHC-I molecules resistant
      to US11-induced degradation. Consistently, deleting the C-terminal cytosolic
      region of Derlin-1 prevented it from binding to MHC-I molecules. Taken together,
      these results suggest that the cytosolic region of Derlin-1 is involved in ERAD
      substrate binding and that this interaction is critical for the Derlin-1-mediated
      dislocation of the MHC-I heavy chain to the cytosol during US11-induced MHC-I
      degradation. 

PMID- 23951316
TI  - Social isolation impairs oral palatal wound healing in sprague-dawley rats: a
      role for miR-29 and miR-203 via VEGF suppression.
AB  - OBJECTIVE: To investigate the effects of social isolation on oral mucosal healing
      in rats, and to determine if wound-associated genes and microRNAs (miRNAs) may
      contribute to this response. METHODS: Rats were group housed or socially isolated
      for 4 weeks before a 3.5 mm wound was placed on the hard oral palate. Wound
      closure was assessed daily and tissues were collected for determination of gene
      expression levels and miRNAs (i.e., miR-29a,b,c and miR-203). The predicted
      target of these microRNAs (i.e., vascular endothelial growth factor A, VEGFA) was
      functionally validated. RESULTS: Social isolation stress delayed the healing
      process of oral palatal mucosal wounds in rats. Lower mRNA levels of interleukin
      1beta (IL1beta), macrophage inflammatory protein-1alpha (MIP1alpha), fibroblast
      growth factor 7 (FGF7), and VEGFA were found in the biopsied tissues of isolated
      animals on days 1 and/or 3 post-wounding. Intriguingly, the isolated rats
      persistently exhibited higher levels of miR-29 family members and miR-203. Our
      results confirmed that VEGFA is a direct target of these miRNAs, as both miR
      29a,c and miR-203 strongly and specifically suppressed endogenous VEGFA
      expression in vitro. CONCLUSIONS: This study in rats demonstrates for the first
      time that social isolation delays oral mucosal healing, and suggests a potential
      role for healing-associated gene and miRNA interactions during this process via
      modulation of VEGF expression.

PMID- 23951317
TI  - PhenoTimer: software for the visual mapping of time-resolved phenotypic
      landscapes.
AB  - Timing common and specific modulators of disease progression is crucial for
      treatment, but the understanding of the underlying complex system of interactions
      is limited. While attempts at elucidating this experimentally have produced
      enormous amounts of phenotypic data, tools that are able to visualize and analyze
      them are scarce and the insight obtained from the data is often unsatisfactory.
      Linking and visualizing processes from genes to phenotypes and back, in a
      temporal context, remains a challenge in systems biology. We introduce
      PhenoTimer, a 2D/3D visualization tool for the mapping of time-resolved
      phenotypic links in a genetic context. It uses a novel visualization approach for
      relations between morphological defects, pathways or diseases, to enable fast
      pattern discovery and hypothesis generation. We illustrate its capabilities of
      tracing dynamic motifs on cell cycle datasets that explore the phenotypic order
      of events upon perturbations of the system, transcriptional activity programs and
      their connection to disease. By using this tool we are able to fine-grain
      regulatory programs for individual time points of the cell cycle and better
      understand which patterns arise when these programs fail. We also illustrate a
      way to identify common mechanisms of misregulation in diseases and drug abuse. 

PMID- 23951318
TI  - The flavonoid pathway regulates the petal colors of cotton flower.
AB  - Although biochemists and geneticists have studied the cotton flower for more than
      one century, little is known about the molecular mechanisms underlying the
      dramatic color change that occurs during its short developmental life following
      blooming. Through the analysis of world cotton germplasms, we found that all of
      the flowers underwent color changes post-anthesis, but there is a diverse array
      of petal colors among cotton species, with cream, yellow and red colors
      dominating the color scheme. Genetic and biochemical analyses indicated that both
      the original cream and red colors and the color changes post-anthesis were
      related to flavonoid content. The anthocyanin content and the expression of
      biosynthesis genes were both increased from blooming to one day post-anthesis
      (DPA) when the flower was withering and undergoing abscission. Our results
      indicated that the color changes and flavonoid biosynthesis of cotton flowers
      were precisely controlled and genetically regulated. In addition, flavonol
      synthase (FLS) genes involved in flavonol biosynthesis showed specific expression
      at 11 am when the flowers were fully opened. The anthocyanidin reductase (ANR)
      genes, which are responsible for proanthocyanidins biosynthesis, showed the
      highest expression at 6 pm on 0 DPA, when the flowers were withered. Light showed
      primary, moderate and little effects on flavonol, anthocyanin and
      proanthocyanidin biosynthesis, respectively. Flavonol biosynthesis was in
      response to light exposure, while anthocyanin biosynthesis was involved in flower
      color changes. Further expression analysis of flavonoid genes in flowers of wild
      type and a flavanone 3-hydroxylase (F3H) silenced line showed that the
      development of cotton flower color was controlled by a complex interaction
      between genes and light. These results present novel information regarding
      flavonoids metabolism and flower development. 

PMID- 23951320
TI  - Upregulation of miR-96 enhances cellular proliferation of prostate cancer cells
      through FOXO1.
AB  - Aberrant expression of miR-96 in prostate cancer has previously been reported.
      However, the role and mechanism of action of miR-96 in prostate cancer has not
      been determined. In this study, the diagnostic and prognostic properties of miR
      96 expression levels were investigated by qRT-PCR in two well documented prostate
      cancer cohorts. The miR-96 expression was found to be significantly higher in
      prostate cancer patients and correlate with WHO grade, and decreased overall
      survival time; patients with low levels of miR-96 lived 1.5 years longer than
      patients with high miR-96 levels. The therapeutic potential was further
      investigated in vitro, showing that ectopic levels of miR-96 enhances growth and
      cellular proliferation in prostate cancer cells, implying that miR-96 has
      oncogenic properties in this setting. We demonstrate that miR-96 expression
      decreases the transcript and protein levels of FOXO1 by binding to one of two
      predicted binding sites in the FOXO1 3'UTR sequence. Blocking this binding site
      completely inhibited the growth enhancement conveyed by miR-96. This finding was
      corroborated in a large external prostate cancer patient cohort where miR-96
      expression inversely correlated to FOXO1 expression. Taken together these
      findings indicate that miR-96 plays a key role in prostate cancer cellular
      proliferation and can enhance prostate cancer progression. This knowledge might
      be utilized for the development of novel therapeutic tools for prostate cancer. 

PMID- 23951319
TI  - A high throughput in vivo assay for taste quality and palatability.
AB  - Taste quality and palatability are two of the most important properties measured
      in the evaluation of taste stimuli. Human panels can report both aspects, but are
      of limited experimental flexibility and throughput capacity. Relatively efficient
      animal models for taste evaluation have been developed, but each of them is
      designed to measure either taste quality or palatability as independent
      experimental endpoints. We present here a new apparatus and method for high
      throughput quantification of both taste quality and palatability using rats in an
      operant taste discrimination paradigm. Cohorts of four rats were trained in a
      modified operant chamber to sample taste stimuli by licking solutions from a 96
      well plate that moved in a randomized pattern beneath the chamber floor. As a
      rat's tongue entered the well it disrupted a laser beam projecting across the top
      of the 96-well plate, consequently producing two retractable levers that operated
      a pellet dispenser. The taste of sucrose was associated with food reinforcement
      by presses on a sucrose-designated lever, whereas the taste of water and other
      basic tastes were associated with the alternative lever. Each disruption of the
      laser was counted as a lick. Using this procedure, rats were trained to
      discriminate 100 mM sucrose from water, quinine, citric acid, and NaCl with 90
      100% accuracy. Palatability was determined by the number of licks per trial and,
      due to intermediate rates of licking for water, was quantifiable along the entire
      spectrum of appetitiveness to aversiveness. All 96 samples were evaluated within
      90 minute test sessions with no evidence of desensitization or fatigue. The
      technology is capable of generating multiple concentration-response functions
      within a single session, is suitable for in vivo primary screening of tastant
      libraries, and potentially can be used to evaluate stimuli for any taste system. 

PMID- 23951321
TI  - An investigation into the strength of the association and agreement levels
      between subjective and objective sleep duration in adolescents.
AB  - STUDY OBJECTIVES: The majority of adolescent sleep research has utilized self
      reported sleep duration and some have based information on a solitary question.
      Whilst some have claimed to have validated sleep survey data with objective
      actigraphy measures in adolescents, the statistical approach applied only
      demonstrates the strength of the association between subjective and objective
      sleep duration data and does not reflect if these different methods actually
      agree. METHODS: Data were collected as part of the Midlands Adolescents Schools
      Sleep Education Study (MASSES). Adolescents (n=225) aged 11-13 years provided
      estimates for weekday, weekend and combined sleep duration based on self-reported
      survey data, a 7-day sleep diary, and wrist-worn actigraphy. RESULTS: We assessed
      the strength of the relationship as well as agreement levels between subjective
      and objectively determined sleep duration (weekday, weekend and combined).
      Subjective diary sleep duration was significantly correlated with actigraphy
      estimates for weekday and weekend sleep duration r=0.30, p <= 0.001 and r=0.31, p
      <= 0.001 respectively. Pitman's test demonstrated no significant difference in
      the variance between weekend sleep duration (r=0.09, p=0.16) and combined sleep
      duration (r=0.12, p=0.08) indicating acceptable agreement between actigraphy and
      sleep diary sleep duration only. Self-reported sleep duration estimates (weekday,
      weekend and combined) did not agree with actigraphy determined sleep duration.
      CONCLUSIONS: Sleep diaries are a cost-effective alternative to
      survey/questionnaire data. Self-reported measures of sleep duration in
      adolescents do not agree with actigraphy measures and should be avoided where
      possible. Previous adolescent sleep studies that have utilized self-reported
      survey data may not provide a complete representation of sleep on the outcome
      measure of interest.

PMID- 23951323
TI  - A novel high throughput biochemical assay to evaluate the HuR protein-RNA complex
      formation.
AB  - The RNA binding protein HuR/ELAVL1 binds to AU-rich elements (AREs) promoting the
      stabilization and translation of a number of mRNAs into the cytoplasm, dictating
      their fate. We applied the AlphaScreen technology using purified human HuR
      protein, expressed in a mammalian cell-based system, to characterize in vitro its
      binding performance towards a ssRNA probe whose sequence corresponds to the are
      present in TNFalpha 3' untranslated region. We optimized the method to titrate
      ligands and analyzed the kinetic in saturation binding and time course
      experiments, including competition assays. The method revealed to be a successful
      tool for determination of HuR binding kinetic parameters in the nanomolar range,
      with calculated Kd of 2.5+/-0.60 nM, k on of 2.76+/-0.56*10(6) M(-1) min(-1), and
      k off of 0.007+/-0.005 min(-1). We also tested the HuR-RNA complex formation by
      fluorescent probe-based RNA-EMSA. Moreover, in a 384-well plate format we
      obtained a Z-factor of 0.84 and an averaged coefficient of variation between
      controls of 8%, indicating that this biochemical assay fulfills criteria of
      robustness for a targeted screening approach. After a screening with 2000 small
      molecules and secondary verification with RNA-EMSA we identified mitoxantrone as
      an interfering compound with rHuR and TNFalpha probe complex formation. Notably,
      this tool has a large versatility and could be applied to other RNA Binding
      Proteins recognizing different RNA, DNA, or protein species. In addition, it
      opens new perspectives in the identification of small-molecule modulators of RNA
      binding proteins activity. 

PMID- 23951322
TI  - Improvement of a predictive model of castration-resistant prostate cancer:
      functional genetic variants in TGFbeta1 signaling pathway modulation.
AB  - Prostate cancer (PC) is the most frequently diagnosed cancer in men. The
      acquisition of castration-resistant (CR) phenotype is associated with the
      activation of signaling pathways mediated by growth factors. The TGFbeta1 and its
      receptors have an important role in tumor progression, being the pro-apoptotic
      function modulated by the expression of TGFBR2. A single nucleotide polymorphism 
      875 G > A in TGFBR2 gene has been described, which may influence the expression
      levels of the receptor. Our purpose was to investigate the potential role of
      TGFBR2-875G>A in PC risk and in the response to androgen deprivation therapy
      (ADT). TGFBR2-875G>A polymorphism was studied by allelic discrimination using
      real-time polymerase chain reaction (PCR) in 891 patients with PC and 874
      controls. A follow-up study was undertaken to evaluate response to ADT. The
      TGFBR2 and SMAD7 mRNA expression were analyzed by a quantitative real-time PCR.
      We found that TGFBR2-875GG homozygous patients present lower expression levels of
      TGFBR2 mRNA (AA/AG: 2(-DeltaDeltaCT) =1.5, P=0.016). GG genotype was also
      associated with higher Gleason grade (OR=1.51, P=0.019) and increased risk of an
      early relapse after ADT (HR=1.47, P=0.024). The concordance (c) index analysis
      showed that the definition of profiles that contains information regarding tumor
      characteristics associated with genetic information present an increased capacity
      to predict the risk for CR development (c-index model 1: 0.683 vs model 2: 0.736
      vs model 3: 0.746 vs model 4: 0.759). The TGFBR2-875G>A contribution to an early
      relapse in ADT patients, due to changes in mRNA expression, supports the
      involvement of TGFbeta1 pathway in CRPC. Furthermore, according to our results,
      we hypothesize the potential benefits of the association of genetic information
      in predictive models of CR development. 

PMID- 23951324
TI  - Haploid meiosis in Arabidopsis: double-strand breaks are formed and repaired but
      without synapsis and crossovers.
AB  - Two hallmark features of meiosis are i) the formation of crossovers (COs) between
      homologs and ii) the production of genetically-unique haploid spores that will
      fuse to restore the somatic ploidy level upon fertilization. In this study we
      analysed meiosis in haploid Arabidopsis thaliana plants and a range of haploid
      mutants to understand how meiosis progresses without a homolog. Extremely low
      chiasma frequency and very limited synapsis occurred in wild-type haploids. The
      resulting univalents segregated in two uneven groups at the first division, and
      sister chromatids segregated to opposite poles at the second division, leading to
      the production of unbalanced spores. DNA double-strand breaks that initiate
      meiotic recombination were formed, but in half the number compared to diploid
      meiosis. They were repaired in a RAD51- and REC8-dependent manner, but
      independently of DMC1, presumably using the sister chromatid as a template.
      Additionally, turning meiosis into mitosis (MiMe genotype) in haploids resulted
      in the production of balanced haploid gametes and restoration of fertility. The
      variability of the effect on meiosis of the absence of homologous chromosomes in
      different organisms is then discussed. 

PMID- 23951325
TI  - The relative composition of the inflammatory infiltrate as an additional tool for
      synovial tissue classification.
AB  - OBJECTIVES: Traditionally, differences in absolute numbers of cells expressing a
      certain marker (e.g., positive staining cells per mm2) have been used in
      immunohistological synovial tissue classification. We have begun to evaluate the
      relative composition of the inflammatory infiltrates, i.e. percentages of
      inflammatory cell types in inflammatory infiltrates, as an alternate
      classification tool that may potentially improve tissue diagnostics, subgrouping
      in clinical trials, and understanding of pathogenesis of inflammatory and
      noninflammatory arthropathies. METHODS: Synovial tissue specimens (normal
      synovium, n=15; orthopedic arthropathies, n=6; osteoarthritis, n=26; early
      undifferentiated arthritis, n=10; rheumatoid arthritis, n=26; chronic septic
      arthritis, n=11) were stained for CD15, CD68, CD3, CD20, and CD38. Densities of
      cells expressing a given marker were determined in the superficial subintima.
      Binary and multicategory receiver operating characteristic (ROC) analysis and
      naive Bayes classifier were used to compare the abilities of (1) the absolute
      densities of cells expressing a given marker (absolute method) with (2) the
      percentages of these cells in the inflammatory cell population (relative method)
      to differentiate among the six tissue classes. RESULTS: The inflammatory
      infiltrates in normal synovium and the orthopedic arthropathies consisted almost
      exclusively of CD68+ and CD3+ cells. Notable fractions of CD20+ and CD38+ cells
      appeared in a subset of osteoarthritis samples, and increased further in early,
      rheumatoid and chronic septic arthritis. ROC analyses and naive Bayes classifier
      ranked the absolute method above the relative method in terms of overall
      discriminatory ability. The relative method became slightly superior when the
      samples were also stratified according to the total number of inflammatory
      cells/mm2. CONCLUSIONS: This exploratory investigation featuring a variety of
      joint disorders revealed that measuring the relative proportions of inflammatory
      cell types may aid in synovial tissue classification if the samples are also
      stratified according to the intensity of inflammation.

PMID- 23951326
TI  - A comparison of the recruitment success of introduced and native species under
      natural conditions.
AB  - It is commonly accepted that introduced species have recruitment advantages over
      native species. However, this idea has not been widely tested, and those studies
      that have compared survival of introduced and native species have produced mixed
      results. We compiled data from the literature on survival through germination
      (seed to seedling survival), early seedling survival (survival through one week
      from seedling emergence) and survival to adulthood (survival from germination to
      first reproduction) under natural conditions for 285 native and 63 introduced
      species. Contrary to expectations, we found that introduced and native species do
      not significantly differ in survival through germination, early seedling
      survival, or survival from germination to first reproduction. These comparisons
      remained non-significant after accounting for seed mass, longevity and when
      including a random effect for site. Results remained consistent after excluding
      naturalized species from the introduced species data set, after performing
      phylogenetic independent contrasts, and after accounting for the effect of life
      form (woody/non-woody). Although introduced species sometimes do have advantages
      over native species (for example, through enemy release, or greater phenotypic
      plasticity), our findings suggest that the overall advantage conferred by these
      factors is either counterbalanced by advantages of native species (such as
      superior adaptation to local conditions) or is simply too small to be detected at
      a broad scale. 

PMID- 23951327
TI  - Insulin-producing cells derived from human embryonic stem cells: comparison of
      definitive endoderm- and nestin-positive progenitor-based differentiation
      strategies.
AB  - Human embryonic stem cells (hESCs) are pluripotent and capable of undergoing
      multilineage differentiation into highly specialized cells including pancreatic
      islet cells. Thus, they represent a novel alternative source for targeted
      therapies and regenerative medicine for diabetes. Significant progress has been
      made in differentiating hESCs toward pancreatic lineages. One approach is based
      on the similarities of pancreatic beta cell and neuroepithelial development.
      Nestin-positive cells are selected as pancreatic beta cell precursors and further
      differentiated to secrete insulin. The other approach is based on our knowledge
      of developmental biology in which the differentiation protocol sequentially
      reproduces the individual steps that are known in normal beta cell ontogenesis
      during fetal pancreatic development. In the present study, the hESC cell line
      PKU1.1 was induced to differentiate into insulin-producing cells (IPCs) using
      both protocols. The differentiation process was dynamically investigated and the
      similarities and differences between both strategies were explored. Our results
      show that IPCs can be successfully induced with both differentiation strategies.
      The resulting IPCs from both protocols shared many similar features with
      pancreatic islet cells, but not mature, functional beta cells. However, these
      differently-derived IPC cell types displayed specific morphologies and different
      expression levels of pancreatic islet development-related markers. These data not
      only broaden our outlook on hESC differentiation into IPCs, but also extend the
      full potential of these processes for regenerative medicine in diabetes. 

PMID- 23951328
TI  - How to maximally support local and regional biodiversity in applied conservation?
      Insights from pond management.
AB  - Biodiversity and nature values in anthropogenic landscapes often depend on land
      use practices and management. Evaluations of the association between management
      and biodiversity remain, however, comparatively scarce, especially in aquatic
      systems. Furthermore, studies also tend to focus on a limited set of organism
      groups at the local scale, whereas a multi-group approach at the landscape scale
      is to be preferred. This study aims to investigate the effect of pond management
      on the diversity of multiple aquatic organism groups (e.g. phytoplankton,
      zooplankton, several groups of macro-invertebrates, submerged and emergent
      macrophytes) at local and regional spatial scales. For this purpose, we performed
      a field study of 39 shallow man-made ponds representing five different management
      types. Our results indicate that fish stock management and periodic pond drainage
      are crucial drivers of pond biodiversity. Furthermore, this study provides
      insight in how the management of eutrophied ponds can contribute to aquatic
      biodiversity. A combination of regular draining of ponds with efforts to keep
      ponds free of fish seems to be highly beneficial for the biodiversity of many
      groups of aquatic organisms at local and regional scales. Regular draining
      combined with a stocking of fish at low biomass is also preferable to infrequent
      draining and lack of fish stock control. These insights are essential for the
      development of conservation programs that aim long-term maintenance of regional
      biodiversity in pond areas across Europe. 

PMID- 23951329
TI  - RNA-seq characterization of spinal cord injury transcriptome in acute/subacute
      phases: a resource for understanding the pathology at the systems level.
AB  - Spinal cord injury (SCI) is a devastating neurological disease without effective
      treatment. To generate a comprehensive view of the mechanisms involved in SCI
      pathology, we applied RNA-Sequencing (RNA-Seq) technology to characterize the
      temporal changes in global gene expression after contusive SCI in mice. We
      sequenced tissue samples from acute and subacute phases (2 days and 7 days after
      injury) and systematically characterized the transcriptomes with the goal of
      identifying pathways and genes critical in SCI pathology. The top enriched
      functional categories include "inflammation response," "neurological disease,"
      "cell death and survival" and "nervous system development." The top enriched
      pathways include LXR/RXR Activation and Atherosclerosis Signaling, etc.
      Furthermore, we developed a systems-based analysis framework in order to identify
      key determinants in the global gene networks of the acute and sub-acute phases.
      Some candidate genes that we identified have been shown to play important roles
      in SCI, which demonstrates the validity of our approach. There are also many
      genes whose functions in SCI have not been well studied and can be further
      investigated by future experiments. We have also incorporated pharmacogenomic
      information into our analyses. Among the genes identified, the ones with existing
      drug information can be readily tested in SCI animal models. Therefore, in this
      study we have described an example of how global gene profiling can be translated
      to identifying genes of interest for functional tests in the future and
      generating new hypotheses. Additionally, the RNA-Seq enables splicing isoform
      identification and the estimation of expression levels, thus providing useful
      information for increasing the specificity of drug design and reducing potential
      side effect. In summary, these results provide a valuable reference data resource
      for a better understanding of the SCI process in the acute and sub-acute phases. 

PMID- 23951330
TI  - Expansion and diversification of BTL ring-H2 ubiquitin ligases in angiosperms:
      putative Rabring7/BCA2 orthologs.
AB  - RING finger E3 ligases are components of the ubiquitin proteasome system (UPS)
      that mediate the transfer of ubiquitin to substrates. Single-subunit RING finger
      E3s binds the E2 ubiquitin-conjugating enzyme and contains recognition sequences
      for the substrate within the same polypeptide. Here we describe the
      characterization of a class of RING finger E3 ligases that is conserved among
      eukaryotes. This class encodes a RING-H2 domain related in sequence to the ATL
      RING-H2 domain, another class of E3 ligases, and a C2/C2 zing finger at the amino
      terminus, formerly described as BZF. In viridiplantae (green algae and land
      plants), we designed this family as BTL for BZF ATLs. BTLs are putative orthologs
      of the mammalian Rabring7/BCA2 RING-H2 E3s that have expanded in angiosperms.
      They are found in numbers ranging from three to thirty-one, which is in contrast
      to the one to three members normally found in animals, fungi, and protists.
      Furthermore, the number of sequence LOGOs generated in angiosperms is four times
      greater than that in other eukaryotes. In contrast to ATLs, which show expansion
      by tandem duplication, tandemly duplicated BTLs are scarce. The mode of action of
      Rabring7/BCA2 and BTLs may be similar since both the Rabring7/BCA2 BZF and the
      ath|BTL4 BZF are likely to mediate the binding of ubiquitin. This study
      introduces valuable information on the evolution and domain structure of the
      Rabring7/BCA2/BTL class of E3 ligases which may be important for core eukaryotic
      genes. 

PMID- 23951331
TI  - Small, dense LDL particles predict changes in intima media thickness and insulin
      resistance in men with type 2 diabetes and prediabetes--a prospective cohort
      study.
AB  - The association of small, dense low-density lipoprotein (sdLDL) particles with an
      increased cardiovascular risk is well established. However, its predictive value
      with regard to glucose metabolism and arterial disease in patients with type 2
      diabetes has not been thoroughly investigated. We conducted a prospective
      longitudinal cohort study in patients with (pre)diabetes who were seen at
      baseline and after two years. sdLDL particles were determined by gradient gel
      electrophoresis. Insulin resistance was estimated by using the homeostatic model
      assessment 2 (HOMA2). Intima media thickness (IMT) and flow-mediated dilation
      (FMD) were assessed by ultrasound measurements. Fifty-nine patients (mean age
      63.0 +/- 12.2 years) were enrolled and 39 were seen at follow-up. IMT increased
      in the whole cohort during follow-up. The change in IMT was predicted by the
      proportion of sdLDL particles at baseline (p=0.03), and the change in FMD was
      predicted by LDL-cholesterol levels at baseline (p=0.049). HOMA2 and changes in
      HOMA2 correlated with the proportion of sdLDL particles and changes in this
      proportion, respectively (p<0.05 for both). Serum resistin levels increased in
      parallel with the increasing sdLDL particle number, while serum adiponectin
      increased only in patients with unaltered sdLDL particle number at follow-up
      (p<0.01 for both). In conclusion, the proportion of small, dense LDL particles
      and changes in this proportion are predictive of changes in intima media
      thickness and insulin resistance, and are closely associated with other
      determinants of an adverse metabolic status. Thus, this parameter extends the
      individual risk assessment beyond the limitations of traditional risk markers in
      patients with dysglycemia. 

PMID- 23951332
TI  - Characterisation and analysis of the Aegilops sharonensis transcriptome, a wild
      relative of wheat in the Sitopsis section.
AB  - Aegilops sharonensis Eig (Sharon goatgrass) is a wild diploid relative of wheat
      within the Sitopsis section of Aegilops. This species represents an untapped
      reservoir of genetic diversity for traits of agronomic importance, especially as
      a source of novel disease resistance. To gain a foothold in this genetic
      resource, we sequenced the cDNA from leaf tissue of two geographically distinct
      Ae. sharonensis accessions (1644 and 2232) using the 454 Life Sciences platform.
      We compared the results of two different assembly programs using different
      parameter sets to generate 13 distinct assemblies in an attempt to maximize
      representation of the gene space in de novo transcriptome assembly. The most
      sensitive assembly (71,029 contigs; N50 674 nts) retrieved 18,684 unique best
      reciprocal BLAST hits (BRBH) against six previously characterised grass proteomes
      while the most specific assembly (30,609 contigs; N50 815 nts) retrieved 15,687
      BRBH. We combined these two assemblies into a set of 62,243 non-redundant
      sequences and identified 139 belonging to plant disease resistance genes of the
      nucleotide binding leucine-rich repeat class. Based on the non-redundant
      sequences, we predicted 37,743 single nucleotide polymorphisms (SNP), equivalent
      to one per 1,142 bp. We estimated the level of heterozygosity as 1.6% in
      accession 1644 and 30.1% in 2232. The Ae. sharonensis leaf transcriptome provides
      a rich source of sequence and SNPs for this wild wheat relative. These sequences
      can be used with existing monocot genome sequences and EST sequence collections
      (e.g. barley, Brachypodium, wheat, rice, maize and Sorghum) to assist with
      genetic and physical mapping and candidate gene identification in Ae.
      sharonensis. These resources provide an initial framework to further build on and
      characterise the genetic and genomic structure of Ae. sharonensis.

PMID- 23951333
TI  - RECQL1 DNA repair helicase: a potential therapeutic target and a proliferative
      marker against ovarian cancer.
AB  - OBJECTIVE: This study analyzed the clinicopathological correlation between
      ovarian cancer (OC) and RECQL1 DNA helicase to assess its therapeutic potential.
      METHODS: Surgically resected OC from 118 retrospective cases, for which paraffin
      blocks and all clinical data were complete, were used in this study. RECQL1 and
      Ki-67 immunostaining were performed on sections to correlate RECQL1 staining with
      subtype and patient survival. Ten OC and two normal cell lines were then examined
      for RECQL1 expression and were treated with siRNA against RECQL1 to assess its
      effect on cell proliferation. RESULTS: Of the 118 cases of adenocarcinoma (50,
      serous; 26, endometrioid; 21, clear cell; 15, mucinous; 6, other histology), 104
      (90%) showed varying levels of RECQL1 expression in the nuclei of OC cells. The
      Cox hazards model confirmed that diffuse and strong staining of RECQL1 was
      correlated with histological type. However, RECQL1 expression did not correlate
      with overall patient survival or FIGO stage. In vitro, RECQL1 expression was
      exceptionally high in rapidly growing OC cell lines, as compared with normal
      cells. Using a time-course analysis of RECQL1-siRNA transfection, we observed a
      significant inhibition in cell proliferation. CONCLUSIONS: RECQL1 DNA helicase is
      a marker of highly proliferative cells. RECQL1-siRNA may offer a new therapeutic
      strategy against various subtypes of OC, including platinum-resistant cancers, or
      in recurrent cancers that gain platinum resistance.

PMID- 23951334
TI  - Canine evolution in sabretoothed carnivores: natural selection or sexual
      selection?
AB  - The remarkable elongated upper canines of extinct sabretoothed carnivorous
      mammals have been the subject of considerable speculation on their adaptive
      function, but the absence of living analogues prevents any direct inference about
      their evolution. We analysed scaling relationships of the upper canines of 20
      sabretoothed feliform carnivores (Nimravidae, Barbourofelidae, Machairodontinae),
      representing both dirk-toothed and scimitar-toothed sabretooth ecomorphs, and 33
      non-sabretoothed felids in relation to body size in order to characterize and
      identify the evolutionary processes driving their development, using the scaling
      relationships of carnassial teeth in both groups as a control. Carnassials
      display isometric allometry in both sabretooths and non-sabretooths, supporting
      their close relationship with meat-slicing, whereas the upper canines of both
      groups display positive allometry with body size. Whereas there is no statistical
      difference in allometry of upper canine height between dirk-toothed and scimitar
      toothed sabretooth ecomorphs, the significantly stronger positive allometry of
      upper canine height shown by sabretooths as a whole compared to non-sabretooths
      reveals that different processes drove canine evolution in these groups. Although
      sabretoothed canines must still have been effective for prey capture and
      processing by hypercarnivorous predators, canine morphology in these extinct
      carnivores was likely to have been driven to a greater extent by sexual selection
      than in non-sabretooths. Scaling relationships therefore indicate the probable
      importance of sexual selection in the evolution of the hypertrophied sabretooth
      anterior dentition. 

PMID- 23951335
TI  - Sleep architecture when sleeping at an unusual circadian time and associations
      with insulin sensitivity.
AB  - Circadian misalignment affects total sleep time, but it may also affect sleep
      architecture. The objectives of this study were to examine intra-individual
      effects of circadian misalignment on sleep architecture and inter-individual
      relationships between sleep stages, cortisol levels and insulin sensitivity.
      Thirteen subjects (7 men, 6 women, age: 24.3+/-2.5 y; BMI: 23.6+/-1.7 kg/m2)
      stayed in a time blinded respiration chamber during three light-entrained
      circadian cycles (3x21h and 3x27h) resulting in a phase advance and a phase
      delay. Sleep was polysomnographically recorded. Blood and salivary samples were
      collected to determine glucose, insulin and cortisol concentrations. Intra
      individually, a phase advance decreased rapid eye movement (REM) sleep and slow
      wave sleep (SWS), increased time awake, decreased sleep and REM sleep latency
      compared to the 24h cycle. A phase delay increased REM sleep, decreased stage 2
      sleep, increased time awake, decreased sleep and REM sleep latency compared to
      the 24h cycle. Moreover, circadian misalignment changed REM sleep distribution
      with a relatively shorter REM sleep during the second part of the night. Inter
      individually, REM sleep was inversely associated with cortisol levels and HOMA-IR
      index. Circadian misalignment, both a phase advance and a phase delay,
      significantly changed sleep architecture and resulted in a shift in rem sleep.
      Inter-individually, shorter REM sleep during the second part of the night was
      associated with dysregulation of the HPA-axis and reduced insulin sensitivity.
      TRIAL REGISTRATION: International Clinical Trials Registry Platform NTR2926
      http://apps.who.int/trialsearch/

PMID- 23951336
TI  - Fibronectin assembly in the crypts of cytokinesis-blocked multilobular cells
      promotes anchorage-independent growth.
AB  - Anchorage-independent growth is a characteristic feature of cancer cells.
      However, it is unclear whether it represents a cause or a consequence of
      tumorigenesis. For normal cells, integrin-mediated adhesion is required for
      completion of the G1 and cytokinesis stages of the cell cycle. This study
      identified a mechanism that can drive anchorage-independent growth if the G1
      checkpoint is suppressed. Cells with defective G1 checkpoint progressed through
      several rounds of the cell cycle in suspension in spite of uncompleted
      cytokinesis, thereby forming bi- and multilobular cells. Aurora B and CEP55 were
      localized to midbodies between the lobes, suggesting that the cytokinesis process
      reached close to abscission. Integrin-mediated re-attachment of such cells
      induced cytokinesis completion uncoupled from karyokinesis in most cells.
      However, a portion of the cells instead lost the constriction and became
      binucleated. Also, long-term suspension culture in soft agar produced colonies
      where the cytokinesis block was overcome. This process was fibronectin-dependent
      since fibronectin-deficient cells did not form colonies unless fibronectin was
      expressed or exogenously added. While fibronectin normally is not deposited on
      non-adherent single cells, bi/multilobular cells accumulated fibronectin in the
      intussusceptions. Based on our data we conclude: 1) Suppression of the G1
      checkpoint allows multiple rounds of the cell cycle in detached cells and thereby
      enables matrix formation on their surface. 2) Uncompleted cytokinesis due to cell
      detachment resumes if integrin interactions are re-formed, allowing colony
      formation in soft agar 3) Such delayed cell division can generate binucleated
      cells, a feature known to cause chromosomal instability. 

PMID- 23951337
TI  - Atomic force microscopy analysis of the role of major DNA-binding proteins in
      organization of the nucleoid in Escherichia coli.
AB  - Bacterial genomic DNA is packed within the nucleoid of the cell along with
      various proteins and RNAs. We previously showed that the nucleoid in log phase
      cells consist of fibrous structures with diameters ranging from 30 to 80 nm, and
      that these structures, upon RNase A treatment, are converted into homogeneous
      thinner fibers with diameter of 10 nm. In this study, we investigated the role of
      major DNA-binding proteins in nucleoid organization by analyzing the nucleoid of
      mutant Escherichia coli strains lacking HU, IHF, H-NS, StpA, Fis, or Hfq using
      atomic force microscopy. Deletion of particular DNA-binding protein genes altered
      the nucleoid structure in different ways, but did not release the naked DNA even
      after the treatment with RNase A. This suggests that major DNA-binding proteins
      are involved in the formation of higher order structure once 10-nm fiber
      structure is built up from naked DNA. 

PMID- 23951338
TI  - Basement membrane-rich organoids with functional human blood vessels are
      permissive niches for human breast cancer metastasis.
AB  - Metastatic breast cancer is the leading cause of death by malignancy in women
      worldwide. Tumor metastasis is a multistep process encompassing local invasion of
      cancer cells at primary tumor site, intravasation into the blood vessel, survival
      in systemic circulation, and extravasation across the endothelium to metastasize
      at a secondary site. However, only a small percentage of circulating cancer cells
      initiate metastatic colonies. This fact, together with the inaccessibility and
      structural complexity of target tissues has hampered the study of the later steps
      in cancer metastasis. In addition, most data are derived from in vivo models
      where critical steps such as intravasation/extravasation of human cancer cells
      are mediated by murine endothelial cells. Here, we developed a new mouse model to
      study the molecular and cellular mechanisms underlying late steps of the
      metastatic cascade. We have shown that a network of functional human blood
      vessels can be formed by co-implantation of human endothelial cells and
      mesenchymal cells, embedded within a reconstituted basement membrane-like matrix
      and inoculated subcutaneously into immunodeficient mice. The ability of
      circulating cancer cells to colonize these human vascularized organoids was next
      assessed in an orthotopic model of human breast cancer by bioluminescent imaging,
      molecular techniques and immunohistological analysis. We demonstrate that
      disseminated human breast cancer cells efficiently colonize organoids containing
      a functional microvessel network composed of human endothelial cells, connected
      to the mouse circulatory system. Human breast cancer cells could be clearly
      detected at different stages of the metastatic process: initial arrest in the
      human microvasculature, extravasation, and growth into avascular micrometastases.
      This new mouse model may help us to map the extravasation process with
      unprecedented detail, opening the way for the identification of relevant targets
      for therapeutic intervention.

PMID- 23951339
TI  - Genetic characterization of the gypsy moth from China (Lepidoptera, Lymantriidae)
      using inter simple sequence repeats markers.
AB  - This study provides the first genetic characterization of the gypsy moth from
      China (Lymantriadispar), one of the most recognized pests of forests and
      ornamental trees in the world. We assessed genetic diversity and structure in
      eight geographic populations of gypsy moths from China using five polymorphic
      Inter simple sequence repeat markers, which produced reproducible banding
      patterns. We observed 102 polymorphic loci across the 176 individuals sampled.
      Overall genetic diversity (Nei's, H) was 0.2357, while the mean genetic diversity
      within geographic populations was 0.1845 +/- 0.0150. The observed genetic
      distance among the eight populations ranged from 0.0432 to 0.1034. Clustering
      analysis (using an unweighted pair-group method with arithmetic mean and
      multidimensional scaling), revealed strong concordance between the strength of
      genetic relationships among populations and their geographic proximity. Analysis
      of molecular variance demonstrated that 25.43% of the total variability (F ST =
      0.2543, P < 0.001) was attributable to variation among geographic populations.
      The results of our analyses investigating the degree of polymorphism, genetic
      diversity (Nei's and Shannon) and genetic structure, suggest that individuals
      from Hebei may be better able to adapt to different environments and to disperse
      to new habitats. This study provides crucial genetic information needed to assess
      the distribution and population dynamics of this important pest species of global
      concern. 

PMID- 23951340
TI  - Bilateral descending hypothalamic projections to the spinal trigeminal nucleus
      caudalis in rats.
AB  - Several lines of evidence suggest that the hypothalamus is involved in trigeminal
      pain processing. However, the organization of descending hypothalamic projections
      to the spinal trigeminal nucleus caudalis (Sp5C) remains poorly understood.
      Microinjections of the retrograde tracer, fluorogold (FG), into the Sp5C, in
      rats, reveal that five hypothalamic nuclei project to the Sp5C: the
      paraventricular nucleus, the lateral hypothalamic area, the perifornical
      hypothalamic area, the A11 nucleus and the retrochiasmatic area. Descending
      hypothalamic projections to the Sp5C are bilateral, except those from the
      paraventricular nucleus which exhibit a clear ipsilateral predominance. Moreover,
      the density of retrogradely FG-labeled neurons in the hypothalamus varies
      according to the dorso-ventral localization of the Sp5C injection site. There are
      much more labeled neurons after injections into the ventrolateral part of the
      Sp5C (where ophthalmic afferents project) than after injections into its
      dorsomedial or intermediate parts (where mandibular and maxillary afferents,
      respectively, project). These results demonstrate that the organization of
      descending hypothalamic projections to the spinal dorsal horn and Sp5C are
      different. Whereas the former are ipsilateral, the latter are bilateral.
      Moreover, hypothalamic projections to the Sp5C display somatotopy, suggesting
      that these projections are preferentially involved in the processing of meningeal
      and cutaneous inputs from the ophthalmic branch of the trigeminal nerve in rats.
      Therefore, our results suggest that the control of trigeminal and spinal dorsal
      horn processing of nociceptive information by hypothalamic neurons is different
      and raise the question of the role of bilateral, rather than unilateral,
      hypothalamic control. 

PMID- 23951342
TI  - The effect of $1, $5 and $10 stakes in an online dictator game.
AB  - The decision rules underpinning human cooperative behaviour are often
      investigated under laboratory conditions using monetary incentives. A major
      concern with this approach is that stake size may bias subjects' decisions. This
      concern is particularly acute in online studies, where stakes are often far lower
      than those used in laboratory or field settings. We address this concern by
      conducting a Dictator Game using Amazon Mechanical Turk. In this two-player game,
      one player (the dictator) determines the division of an endowment between himself
      and the other player. We recruited subjects from India and the USA to play an
      online Dictator Game. Dictators received endowments of $1, $5 or $10. We
      collected two batches of data over two consecutive years. We found that players
      from India were less generous when playing with a $10 stake. By contrast, the
      effect of stake size among players from the USA was very small. This study
      indicates that the effects of stake size on decision making in economic games may
      vary across populations. 

PMID- 23951341
TI  - Equivalent T cell epitope promiscuity in ecologically diverse human pathogens.
AB  - BACKGROUND: The HLA (human leukocyte antigen) molecules that present pathogen
      derived epitopes to T cells are highly diverse. Correspondingly, many pathogens
      such as HIV evolve epitope variants in order to evade immune recognition. In
      contrast, another persistent human pathogen, Mycobacterium tuberculosis, has
      highly conserved epitope sequences. This raises the question whether there is
      also a difference in the ability of these pathogens' epitopes to bind diverse HLA
      alleles, referred to as an epitope's binding promiscuity. To address this
      question, we compared the in silico HLA binding promiscuity of T cell epitopes
      from pathogens with distinct infection strategies and outcomes of human exposure.
      METHODS: We used computer algorithms to predict the binding affinity of
      experimentally-verified microbial epitope peptides to diverse HLA-DR, HLA-A and
      HLA-B alleles. We then analyzed binding promiscuity of epitopes derived from HIV
      and M. tuberculosis. We also analyzed promiscuity of epitopes from Streptococcus
      pyogenes, which is known to exhibit epitope diversity, and epitopes of Bacillus
      anthracis and Clostridium tetani toxins, as these bacteria do not depend on human
      hosts for their survival or replication, and their toxin antigens are highly
      immunogenic human vaccines. RESULTS: We found that B. anthracis and C. tetani
      epitopes were the most promiscuous of the group that we analyzed. However, there
      was no consistent difference or trend in promiscuity in epitopes contained in
      HIV, M. tuberculosis, and S. pyogenes. CONCLUSIONS: Our results show that human
      pathogens with distinct immune evasion strategies and epitope diversities exhibit
      equivalent levels of T cell epitope promiscuity. These results indicate that
      differences in epitope promiscuity do not account for the observed differences in
      epitope variation and conservation.

PMID- 23951343
TI  - Leukocyte proliferation and immune modulator production in patients with chronic
      kidney disease.
AB  - INTRODUCTION: In Chronic Kidney Disease (CKD), immune cells are affected by
      uremic retention toxins. Given this effect, we analyzed lymphocyte proliferative
      response and immune modulators production following in vitro stimulation.
      METHODS: Whole blood was drawn from healthy controls, patients with eGFR <20
      ml/min/1.73 m(2) (Pre-dialysis, CKD stages 4 and 5) and hemodialysis patients
      (stage 5D). Peripheral cells were incubated for six days with pokeweed mitogen,
      concanavalin A, Staphylococcus enterotoxin A or influenza A vaccine. Peripheral
      lymphocyte proliferation was then analyzed by the "Flow-cytometric Assay of
      Specific Cell-mediated Immune response in Activated whole blood" (FASCIA) method,
      and cytokine profile in the cell supernatants was analyzed by the Milliplex multi
      array method. RESULTS: The absolute number of lymphoblasts in response to
      mitogenic stimulation and the number of cells in each CD4+ and CD8+ subpopulation
      were similar comparing the three groups, except for a single decline in number of
      lymphoblasts after stimulation with Staphylococcus enterotoxin A, comparing
      dialysis patients with healthy controls. Levels of interleukin (IL)-2 (p=0.026), 
      10 (p=0.019) and -15 (p=0.027) in the Staphylococcus enterotoxin A-stimulated
      supernatant were lower in hemodialysis patients compared to healthy controls.
      Levels of IL-15 (p=0.017) from pre-dialysis patients and levels of IL-5 (p=0.019)
      from hemodialysis patients in influenza A vaccine-stimulated supernatants were
      also lower compared to controls. In pokeweed mitogen-stimulated supernatant, IL-2
      levels (p=0.013) were lower in hemodialysis patients compared to pre-dialysis
      patients. TNF-alpha, IL-10, IL-12, IL-15, IL-8, MCP-1, IP-10, IFN-alpha2, IL
      1alpha and eotaxin levels were all significantly higher in plasma obtained from
      CKD patients. CONCLUSION: Our results suggest that T-cells from CKD patients have
      similar proliferative response to stimulation compared with healthy individuals.
      Moreover, however the immune cells show inability to produce selected cytokines,
      most likely due to the uremic milieu or dialysis procedure.

PMID- 23951344
TI  - Specific inhibition of tumor cells by oncogenic EGFR specific silencing by RNA
      interference.
AB  - Anticancer agents that have minimal effects on normal cells and tissues are ideal
      cancer drugs. Here, we show specific inhibition of human cancer cells carrying
      oncogenic mutations in the epidermal growth factor receptor (EGFR) gene by means
      of oncogenic allele-specific RNA interference (RNAi), both in vivo and in vitro.
      The allele-specific RNAi (ASP-RNAi) treatment did not affect normal cells or
      tissues that had no target oncogenic allele, whereas the suppression of a normal
      EGFR allele by a conventional in vivo RNAi caused adverse effects, i.e., normal
      EGFR is vital. Taken together, our current findings suggest that specific
      inhibition of oncogenic EGFR alleles without affecting the normal EGFR allele may
      provide a safe treatment approach for cancer patients and that ASP-RNAi treatment
      may be capable of becoming a safe and effective, anticancer treatment method. 

PMID- 23951345
TI  - Identification of new dystroglycan complexes in skeletal muscle.
AB  - The dystroglycan complex contains the transmembrane protein beta-dystroglycan and
      its interacting extracellular mucin-like protein alpha-dystroglycan. In skeletal
      muscle fibers, the dystroglycan complex plays an important structural role by
      linking the cytoskeletal protein dystrophin to laminin in the extracellular
      matrix. Mutations that affect any of the proteins involved in this structural
      axis lead to myofiber degeneration and are associated with muscular dystrophies
      and congenital myopathies. Because loss of dystrophin in Duchenne muscular
      dystrophy (DMD) leads to an almost complete loss of dystroglycan complexes at the
      myofiber membrane, it is generally assumed that the vast majority of dystroglycan
      complexes within skeletal muscle fibers interact with dystrophin. The residual
      dystroglycan present in dystrophin-deficient muscle is thought to be preserved by
      utrophin, a structural homolog of dystrophin that is up-regulated in dystrophic
      muscles. However, we found that dystroglycan complexes are still present at the
      myofiber membrane in the absence of both dystrophin and utrophin. Our data show
      that only a minority of dystroglycan complexes associate with dystrophin in wild
      type muscle. Furthermore, we provide evidence for at least three separate pools
      of dystroglycan complexes within myofibers that differ in composition and are
      differentially affected by loss of dystrophin. Our findings indicate a more
      complex role of dystroglycan in muscle than currently recognized and may help
      explain differences in disease pathology and severity among myopathies linked to
      mutations in DAPC members. 

PMID- 23951346
TI  - Predictors of death during tuberculosis treatment in TB/HIV co-infected patients
      in Malaysia.
AB  - BACKGROUND: Mortality among TB/HIV co-infected patients is still high
      particularly in developing countries. This study aimed to determine the
      predictors of death in TB/HIV co-infected patients during TB treatment. METHODS:
      We reviewed medical records at the time of TB diagnosis and subsequent follow-up
      of all newly registered TB patients with HIV co-infection at TB clinics in the
      Institute of Respiratory Medicine and three public hospitals in the Klang Valley
      between January 2010 and September 2010. We reviewed these medical records again
      twelve months after their initial diagnosis to determine treatment outcomes and
      survival. We analysed using Kaplan-Meier and conducted multivariate Cox
      proportional hazards analysis to identify predictors of death during TB treatment
      in TB/HIV co-infected patients. RESULTS: Of the 227 patients studied, 53 (23.3%)
      had died at the end of the study with 40% of deaths within two months of TB
      diagnosis. Survival at 2, 6 and 12 months after initiating TB treatment were
      90.7%, 82.8% and 78.8% respectively. After adjusting for other factors, death in
      TB/HIV co-infected patients was associated with being Malay (aHR 4.48; 95%CI 1.73
      11.64), CD4 T-lymphocytes count < 200 cells/ul (aHR 3.89; 95% CI 1.20-12.63),
      three or more opportunistic infections (aHR 3.61; 95% CI 1.04-12.55), not
      receiving antiretroviral therapy (aHR 3.21; 95% CI 1.76-5.85) and increase per
      10(3) total white blood cell count per microliter (aHR 1.12; 95% CI 1.05-1.20).
      CONCLUSION: TB/HIV co-infected patients had a high case fatality rate during TB
      treatment. Initiation of antiretroviral therapy in these patients can improve
      survival by restoring immune function and preventing opportunistic infections.

PMID- 23951347
TI  - LPS structure and PhoQ activity are important for Salmonella Typhimurium
      virulence in the Galleria mellonella infection model [corrected].
AB  - The larvae of the wax moth, Galleria mellonella, have been used experimentally to
      host a range of bacterial and fungal pathogens. In this study we evaluated the
      suitability of G. mellonella as an alternative animal model of Salmonella
      infection. Using a range of inoculum doses we established that the LD50 of
      SalmonellaTyphimurium strain NCTC 12023 was 3.6 * 103 bacteria per larva.
      Further, a set of isogenic mutant strains depleted of known virulence factors was
      tested to identify determinants essential for S. Typhimurium pathogenesis.
      Mutants depleted of one or both of the type III secretion systems encoded by
      Salmonella Pathogenicity Islands 1 and 2 showed no virulence defect. In contrast,
      we observed reduced pathogenic potential of a phoQ mutant indicating an important
      role for the PhoPQ two-component signal transduction system. Lipopolysaccharide
      (LPS) structure was also shown to influence Salmonella virulence in G.
      mellonella. A waaL(rfaL) mutant, which lacks the entire O-antigen (OAg), was
      virtually avirulent, while a wzz(ST)/wzz(fepE) double mutant expressing only a
      very short OAg was highly attenuated for virulence. Furthermore, shortly after
      infection both LPS mutant strains showed decreased replication when compared to
      the wild type in a flow cytometry-based competitive index assay. In this study we
      successfully established a G. mellonella model of S. Typhimurium infection. By
      identifying PhoQ and LPS OAg length as key determinants of virulence in the wax
      moth larvae we proved that there is an overlap between this and other animal
      model systems, thus confirming that the G. mellonella infection model is suitable
      for assessing aspects of Salmonella virulence function.

PMID- 23951348
TI  - Interactions between Abeta and mutated Tau lead to polymorphism and induce
      aggregation of Abeta-mutated tau oligomeric complexes.
AB  - One of the main hallmarks of the fronto-temporal dementia with Parkinsonism
      linked to chromosome 17 (FTDP-17) is the accumulation of neurofibrillary tangles
      in the brain as an outcome of the aggregation of mutated tau protein. This
      process occurs due to a number of genetic mutations in the MAPT gene. One of
      these mutations is the ?K280 mutation in the tau R2 repeat domain, which promotes
      the aggregation vis-a-vis that for the wild-type tau. Experimental studies have
      shown that in Alzheimer's disease Abeta peptide forms aggregates both with itself
      and with wild-type tau. By analogy, in FTDP-17, it is likely that there are
      interactions between Abeta and mutated tau, but the molecular mechanisms
      underlying such interactions remain to be elucidated. Thus, to investigate the
      interactions between Abeta and mutated tau, we constructed fourteen ?K280 mutated
      tau-Abeta17-42 oligomeric complexes. In seven of the mutated tau-Abeta17-42
      oligoemric complexes the mutated tau oligomers exhibited hydrophobic interactions
      in their core domain, and in the other seven mutated tau-Abeta17-42 oligoemric
      complexes the mutated tau oligomers exhibited salt-bridge interactions in their
      core domain. We considered two types of interactions between mutated tau
      oligomers and Abeta oligomers: interactions of one monomer of the Abeta oligomer
      with one monomer of the mutated tau oligomer to form a single-layer conformation,
      and interactions of the entire Abeta oligomer with the entire mutated tau
      oligomer to form a double-layer conformation. We also considered parallel
      arrangements of Abeta trimers alternating with mutated tau trimers in a single
      layer conformation. Our results demonstrate that in the interactions of Abeta and
      mutated tau oligomers, polymorphic mutated tau-Abeta17-42 oligomeric complexes
      were observed, with a slight preference for the double-layer conformation. Abeta
      trimers alternating with mutated tau trimers constituted a structurally stable
      confined beta-structure, albeit one that was energetically less stable than all
      the other constructed models. 

PMID- 23951349
TI  - Endovascular treatment of internal iliac artery stenosis in patients with buttock
      claudication.
AB  - AIM: To assess the technical feasibility and clinical outcome of percutaneous
      transluminal angioplasty (PTA) with and without stent placement for treatment of
      buttock claudication caused by internal iliac artery (IIA) stenosis. METHODS:
      Between September 2001 and July 2011, thirty-four patients with buttock
      claudication underwent endovascular treatment. After angiographic lesion
      evaluation PTA with or without stent placement was performed. Technical success
      was recorded. Clinical outcome post-treatment was assessed at three months post
      intervention and was classified as: 1) complete relief of symptoms, 2) partial
      relief, or 3) no relief of symptoms. Complications during follow-up were
      recorded. RESULTS: Forty-four lesions in 34 symptomatic patients were treated
      with PTA. Eight lesions were treated with additional stent placement. Technical
      success was achieved in 40/44 lesions (91%). Three procedure-related minor
      complications occurred, i.e. asymptomatic conservatively treated intimal
      dissections. After a median of 2.9 months, patients experienced no relief of
      symptoms in 7/34 cases (21%), partial relief in 14/34 cases (41%), and complete
      relief in 13/34 cases (38%). Six patients required a reintervention during follow
      up. CONCLUSION: Endovascular treatment of IIA stenosis has a high technical
      success rate and a low complication rate. Complete or partial relief of symptoms
      is achieved in the majority (79%) of patients.

PMID- 23951350
TI  - Intrinsic photosensitive retinal ganglion cells in the diurnal rodent,
      Arvicanthis ansorgei.
AB  - Intrinsically photosensitive retinal ganglion cells (ipRGCs) represent a new
      class of photoreceptors which support a variety of non-image forming
      physiological functions, such as circadian photoentrainment, pupillary light
      reflex and masking responses to light. In view of the recently proposed role of
      retinal inputs for the regulation of diurnal and nocturnal behavior, we performed
      the first deep analysis of the ipRGC system in a diurnal rodent model,
      Arvicanthisansorgei, and compared the anatomical and physiological properties of
      ipRGCs with those of nocturnal mice. Based on somata location, stratification
      pattern and melanopsin expression, we identified two main ipRGC types in the
      retina of Arvicanthis: M1, constituting 74% of all ipRGCs and non-M1 (consisting
      mainly of the M2 type) constituting the following 25%. The displaced ipRGCs were
      rarely encountered. Phenotypical staining patterns of ganglion cell markers
      showed a preferential expression of Brn3 and neurofilaments in non-M1 ipRGCs. In
      general, the anatomical properties and molecular phenotyping of ipRGCs in
      Arvicanthis resemble ipRGCs of the mouse retina, however the percentage of M1
      cells is considerably higher in the diurnal animal. Multi-electrode array
      recordings (MEA) identified in newborn retinas of Arvicanthis three response
      types of ipRGCs (type I, II and III) which are distinguished by their light
      sensitivity, response strength, latency and duration. Type I ipRGCs exhibited a
      high sensitivity to short light flashes and showed, contrary to mouse type I
      ipRGCs, robust light responses to 10 ms flashes. The morphological, molecular and
      physiological analysis reveals very few differences between mouse and Arvicanthis
      ipRGCs. These data imply that the influence of retinal inputs in defining the
      temporal niche could be related to a stronger cone input into ipRGCs in the cone
      rich Arvicanthis retina, and to the higher sensitivity of type I ipRGCs and
      elevated proportion of M1 cells. 

PMID- 23951351
TI  - Pharmacological inhibition of polysialyltransferase ST8SiaII modulates tumour
      cell migration.
AB  - Polysialic acid (polySia), an alpha-2,8-glycosidically linked polymer of sialic
      acid, is a developmentally regulated post-translational modification
      predominantly found on NCAM (neuronal cell adhesion molecule). Whilst high levels
      are expressed during development, peripheral adult organs do not express polySia
      NCAM. However, tumours of neural crest-origin re-express polySia-NCAM: its
      occurrence correlates with aggressive and invasive disease and poor clinical
      prognosis in different cancer types, notably including small cell lung cancer
      (SCLC), pancreatic cancer and neuroblastoma. In neuronal development, polySia
      NCAM biosynthesis is catalysed by two polysialyltransferases, ST8SiaII and
      ST8SiaIV, but it is ST8SiaII that is the prominent enzyme in tumours. The aim of
      this study was to determine the effect of ST8SiaII inhibition by a small molecule
      on tumour cell migration, utilising cytidine monophosphate (CMP) as a tool
      compound. Using immunoblotting we showed that CMP reduced ST8iaII-mediated
      polysialylation of NCAM. Utilizing a novel HPLC-based assay to quantify
      polysialylation of a fluorescent acceptor (DMB-DP3), we demonstrated that CMP is
      a competitive inhibitor of ST8SiaII (K i = 10 uM). Importantly, we have shown
      that CMP causes a concentration-dependent reduction in tumour cell-surface
      polySia expression, with an absence of toxicity. When ST8SiaII-expressing tumour
      cells (SH-SY5Y and C6-STX) were evaluated in 2D cell migration assays, ST8SiaII
      inhibition led to significant reductions in migration, while CMP had no effect on
      cells not expressing ST8SiaII (DLD-1 and C6-WT). The study demonstrates for the
      first time that a polysialyltransferase inhibitor can modulate migration in
      ST8SiaII-expressing tumour cells. We conclude that ST8SiaII can be considered a
      druggable target with the potential for interfering with a critical mechanism in
      tumour cell dissemination in metastatic cancers. 

PMID- 23951353
TI  - Evaluation of EGFR and RTK signaling in the electrotaxis of lung adenocarcinoma
      cells under direct-current electric field stimulation.
AB  - Physiological electric field (EF) plays a pivotal role in tissue development and
      regeneration. In vitro, cells under direct-current electric field (dcEF)
      stimulation may demonstrate directional migration (electrotaxis) and long axis
      reorientation (electro-alignment). Although the biophysical models and
      biochemical signaling pathways behind cell electrotaxis have been investigated in
      numerous normal cells and cancer cells, the molecular signaling mechanisms in CL1
      lung adenocarcinoma cells have not been identified. Two subclones of CL1 cells,
      the low invasive CL1-0 cells and the highly invasive CL 1-5 cells, were
      investigated in the present study. CL1-0 cells are non-electrotactic while the CL
      1-5 cells are anodally electrotactic and have high expression level of epidermal
      growth factor receptor (EGFR), in this study, we investigated the generally
      accepted hypothesis of receptor tyrosine kinase (RTK) activation in the two cell
      lines under dcEF stimulation. Erbitux, a therapeutic drug containing an anti-EGFR
      monoclonal antibody, cetuximab, was used to investigate the EGFR signaling in the
      electrotaxis of CL 1-5 cells. To investigate RTK phosphorylation and
      intracellular signaling in the CL1 cells, large amount of cellular proteins were
      collected in an airtight dcEF stimulation device, which has advantages of large
      culture area, uniform EF distribution, easy operation, easy cell collection, no
      contamination, and no medium evaporation. Commercial antibody arrays and Western
      blotting were used to study the phosphorylation profiles of major proteins in CL1
      cells under dcEF stimulation. We found that electrotaxis of CL 1-5 cells is serum
      independent and EGFR independent. Moreover, the phosphorylation of Akt and S6
      ribosomal protein (rpS6) in dcEF-stimulated CL1 cells are different from that in
      EGF-stimulated cells. This result suggests that CL1 cells' response to dcEF
      stimulation is not through EGFR-triggered pathways. The new large-scale dcEF
      stimulation device developed in the present work will aid the sample preparation
      for protein-based experiments. 

PMID- 23951352
TI  - Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA)
      isolates of swine origin form robust biofilms.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) colonization of livestock
      animals is common and prevalence rates for pigs have been reported to be as high
      as 49%. Mechanisms contributing to the persistent carriage and high prevalence
      rates of livestock-associated methicillin-resistant Staphylococcus aureus (LA
      MRSA) strains in swine herds and production facilities have not been
      investigated. One explanation for the high prevalence of MRSA in swine herds is
      the ability of these organisms to exist as biofilms. In this report, the ability
      of swine LA-MRSA strains, including ST398, ST9, and ST5, to form biofilms was
      quantified and compared to several swine and human isolates. The contribution of
      known biofilm matrix components, polysaccharides, proteins and extracellular DNA
      (eDNA), was tested in all strains as well. All MRSA swine isolates formed robust
      biofilms similar to human clinical isolates. The addition of Dispersin B had no
      inhibitory effect on swine MRSA isolates when added at the initiation of biofilm
      growth or after pre-established mature biofilms formed. In contrast, the addition
      of proteinase K inhibited biofilm formation in all strains when added at the
      initiation of biofilm growth and was able to disperse pre-established mature
      biofilms. Of the LA-MRSA strains tested, we found ST398 strains to be the most
      sensitive to both inhibition of biofilm formation and dispersal of pre-formed
      biofilms by DNaseI. Collectively, these findings provide a critical first step in
      designing strategies to control or eliminate MRSA in swine herds. 

PMID- 23951354
TI  - xopAC-triggered immunity against Xanthomonas depends on Arabidopsis receptor-like
      cytoplasmic kinase genes PBL2 and RIPK.
AB  - Xanthomonas campestris pv. campestris (Xcc) colonizes the vascular system of
      Brassicaceae and ultimately causes black rot. In susceptible Arabidopsis plants,
      XopAC type III effector inhibits by uridylylation positive regulators of the PAMP
      triggered immunity such as the receptor-like cytoplasmic kinases (RLCK) BIK1 and
      PBL1. In the resistant ecotype Col-0, xopAC is a major avirulence gene of Xcc. In
      this study, we show that both the RLCK interaction domain and the uridylyl
      transferase domain of XopAC are required for avirulence. Furthermore, xopAC can
      also confer avirulence to both the vascular pathogen Ralstonia solanacearum and
      the mesophyll-colonizing pathogen Pseudomonas syringae indicating that xopAC
      specified effector-triggered immunity is not specific to the vascular system. In
      planta, XopAC-YFP fusions are localized at the plasma membrane suggesting that
      XopAC might interact with membrane-localized proteins. Eight RLCK of subfamily
      VII predicted to be localized at the plasma membrane and interacting with XopAC
      in yeast two-hybrid assays have been isolated. Within this subfamily, PBL2 and
      RIPK RLCK genes but not BIK1 are important for xopAC-specified effector-triggered
      immunity and Arabidopsis resistance to Xcc. 

PMID- 23951355
TI  - A novel naturally occurring tandem promoter in modified vaccinia virus ankara
      drives very early gene expression and potent immune responses.
AB  - Modified vaccinia virus Ankara (MVA) has been shown to be suitable for the
      generation of experimental vaccines against cancer and infectious diseases,
      eliciting strong humoral and cellular immune responses. In viral vectored
      vaccines, strong recombinant antigen expression and timing of expression
      influence the quantity and quality of the immune response. Screening of synthetic
      and native poxvirus promoters for strong protein expression in vitro and potent
      immune responses in vivo led to the identification of the MVA13.5L promoter, a
      unique and novel naturally occurring tandem promoter in MVA composed of two 44
      nucleotide long repeated motifs, each containing an early promoter element. The
      MVA13.5L gene is highly conserved across orthopoxviruses, yet its function is
      unknown. The unique structure of its promoter is not found for any other gene in
      the MVA genome and is also conserved in other orthopoxviruses. Comparison of the
      MVA13.5L promoter activity with synthetic poxviral promoters revealed that the
      MVA13.5L promoter produced higher levels of protein early during infection in
      HeLa cells and particularly in MDBK cells, a cell line in which MVA replication
      stops at an early stage before the expression of late genes. Finally, a
      recombinant antigen expressed under the control of this novel promoter induced
      high antibody titers and increased CD8 T cell responses in homologous prime-boost
      immunization compared to commonly used promoters. In particular, the recombinant
      antigen specific CD8 T cell responses dominated over the immunodominant B8R
      vector-specific responses after three vaccinations and even more during the
      memory phase. These results have identified the native MVA13.5L promoter as a new
      potent promoter for use in MVA vectored preventive and therapeutic vaccines. 

PMID- 23951356
TI  - A conservative assessment of the major genetic causes of idiopathic chronic
      pancreatitis: data from a comprehensive analysis of PRSS1, SPINK1, CTRC and CFTR
      genes in 253 young French patients.
AB  - Idiopathic chronic pancreatitis (ICP) has traditionally been defined as chronic
      pancreatitis in the absence of any obvious precipitating factors (e.g. alcohol
      abuse) and family history of the disease. Studies over the past 15 years have
      revealed that ICP has a highly complex genetic architecture involving multiple
      gene loci. Here, we have attempted to provide a conservative assessment of the
      major genetic causes of ICP in a sample of 253 young French ICP patients. For the
      first time, conventional types of mutation (comprising coding sequence variants
      and variants at intron/exon boundaries) and gross genomic rearrangements were
      screened for in all four major pancreatitis genes, PRSS1, SPINK1, CTRC and CFTR.
      For the purposes of the study, synonymous, intronic and 5'- or 3'-untranslated
      region variants were excluded from the analysis except where there was persuasive
      evidence of functional consequences. The remaining sequence variants/genotypes
      were classified into causative, contributory or neutral categories by
      consideration of (i) their allele frequencies in patient and normal control
      populations, (ii) their presumed or experimentally confirmed functional effects,
      (iii) the relative importance of their associated genes in the pathogenesis of
      chronic pancreatitis and (iv) gene-gene interactions wherever applicable.
      Adoption of this strategy allowed us to assess the pathogenic relevance of
      specific variants/genotypes to their respective carriers to an unprecedented
      degree. The genetic cause of ICP could be assigned in 23.7% of individuals in the
      study group. A strong genetic susceptibility factor was also present in an
      additional 24.5% of cases. Taken together, up to 48.2% of the studied ICP
      patients were found to display evidence of a genetic basis for their
      pancreatitis. Whereas these particular proportions may not be extrapolable to all
      ICP patients, the approach employed should serve as a useful framework for
      acquiring a better understanding of the role of genetic factors in causing this
      oligogenic disease. 

PMID- 23951357
TI  - A comprehensive description and evolutionary analysis of 22 grouper (perciformes,
      epinephelidae) mitochondrial genomes with emphasis on two novel genome
      organizations.
AB  - Groupers of the family Epinephelidae are a diverse and economically valuable
      group of reef fishes. To investigate the evolution of their mitochondrial genomes
      we characterized and compared these genomes among 22 species, 17 newly sequenced.
      Among these fishes we identified three distinct genome organizations, two of them
      never previously reported in vertebrates. In 19 of these species, mitochondrial
      genomes followed the typical vertebrate canonical organization with 13 protein
      coding genes, 22 tRNAs, two rRNAs, and a non-coding control region. Differing
      from this, members of genus Variola have an extra tRNA-Ile between tRNA-Val and
      16S rRNA. Evidence suggests that this evolved from tRNA-Val via a duplication
      event due to slipped strand mispairing during replication. Additionally,
      Cephalopholisargus has an extra tRNA-Asp in the midst of the control region,
      likely resulting from long-range duplication of the canonical tRNA-Asp through
      illicit priming of mitochondrial replication by tRNAs. Along with their gene
      contents, we characterized the regulatory elements of these mitochondrial
      genomes' control regions, including putative termination-associated sequences and
      conserved sequence blocks. Looking at the mitochondrial genomic constituents,
      rRNA and tRNA are the most conserved, followed by protein-coding genes, and non
      coding regions are the most divergent. Divergence rates vary among the protein
      coding genes, and the three cytochrome oxidase subunits (COI, II, III) are the
      most conserved, while NADH dehydrogenase subunit 6 (ND6) and the ATP synthase
      subunit 8 (ATP8) are the most divergent. We then tested the phylogenetic utility
      of this new mt genome data using 12 protein-coding genes of 48 species from the
      suborder Percoidei. From this, we provide further support for the elevation of
      the subfamily Epinephelinae to family Epinephelidae, the resurrection of the
      genus Hyporthodus, and the combination of the monotypic genera Anyperodon and
      Cromileptes to genus Epinephelus, and Aethaloperca to genus Cephalopholis. 

PMID- 23951358
TI  - A novel autosomal recessive GJA1 missense mutation linked to Craniometaphyseal
      dysplasia.
AB  - Craniometaphyseal dysplasia (CMD) is a rare sclerosing skeletal disorder with
      progressive hyperostosis of craniofacial bones. CMD can be inherited in an
      autosomal dominant (AD) trait or occur after de novo mutations in the
      pyrophosphate transporter ANKH. Although the autosomal recessive (AR) form of CMD
      had been mapped to 6q21-22 the mutation has been elusive. In this study, we
      performed whole-exome sequencing for one subject with AR CMD and identified a
      novel missense mutation (c.716G>A, p.Arg239Gln) in the C-terminus of the gap
      junction protein alpha-1 (GJA1) coding for connexin 43 (Cx43). We confirmed this
      mutation in 6 individuals from 3 additional families. The homozygous mutation
      cosegregated only with affected family members. Connexin 43 is a major component
      of gap junctions in osteoblasts, osteocytes, osteoclasts and chondrocytes. Gap
      junctions are responsible for the diffusion of low molecular weight molecules
      between cells. Mutations in Cx43 cause several dominant and recessive disorders
      involving developmental abnormalities of bone such as dominant and recessive
      oculodentodigital dysplasia (ODDD; MIM #164200, 257850) and isolated syndactyly
      type III (MIM #186100), the characteristic digital anomaly in ODDD. However,
      characteristic ocular and dental features of ODDD as well as syndactyly are
      absent in patients with the recessive Arg239Gln Cx43 mutation. Bone remodeling
      mechanisms disrupted by this novel Cx43 mutation remain to be elucidated. 

PMID- 23951359
TI  - A transgenic tri-modality reporter mouse.
AB  - Transgenic mouse with a stably integrated reporter gene(s) can be a valuable
      resource for obtaining uniformly labeled stem cells, tissues, and organs for
      various applications. We have generated a transgenic mouse model that
      ubiquitously expresses a tri-fusion reporter gene (fluc2-tdTomato-ttk) driven by
      a constitutive chicken beta-actin promoter. This "Tri-Modality Reporter Mouse"
      system allows one to isolate most cells from this donor mouse and image them for
      bioluminescent (fluc2), fluorescent (tdTomato), and positron emission tomography
      (PET) (ttk) modalities. Transgenic colonies with different levels of tri-fusion
      reporter gene expression showed a linear correlation between all three-reporter
      proteins (R(2)=0.89 for TdTomato vs Fluc, R(2)=0.94 for Fluc vs TTK, R(2)=0.89
      for TdTomato vs TTK) in vitro from tissue lysates and in vivo by optical and PET
      imaging. Mesenchymal stem cells (MSCs) isolated from this transgenics showed high
      level of reporter gene expression, which linearly correlated with the cell
      numbers (R(2)=0.99 for bioluminescence imaging (BLI)). Both BLI (R(2)=0.93) and
      micro-PET (R(2)=0.94) imaging of the subcutaneous implants of Tri-Modality
      Reporter Mouse derived MSCs in nude mice showed linear correlation with the cell
      numbers and across different imaging modalities (R(2)=0.97). Serial imaging of
      MSCs transplanted to mice with acute myocardial infarction (MI) by
      intramyocardial injection exhibited significantly higher signals in MI heart at
      days 2, 3, 4, and 7 (p<0.01). MSCs transplanted to the ischemic hindlimb of nude
      mice showed significantly higher BLI and PET signals in the first 2 weeks that
      dropped by 4(th) week due to poor cell survival. However, laser Doppler perfusion
      imaging revealed that blood circulation in the ischemic limb was significantly
      improved in the MSCs transplantation group compared with the control group. In
      summary, this mouse can be used as a source of donor cells and organs in various
      research areas such as stem cell research, tissue engineering research, and organ
      transplantation. 

PMID- 23951360
TI  - A type-II positive allosteric modulator of alpha7 nAChRs reduces brain injury and
      improves neurological function after focal cerebral ischemia in rats.
AB  - In the absence of clinically-efficacious therapies for ischemic stroke there is a
      critical need for development of new therapeutic concepts and approaches for
      prevention of brain injury secondary to cerebral ischemia. This study tests the
      hypothesis that administration of PNU-120596, a type-II positive allosteric
      modulator (PAM-II) of alpha7 nicotinic acetylcholine receptors (nAChRs), as long
      as 6 hours after the onset of focal cerebral ischemia significantly reduces brain
      injury and neurological deficits in an animal model of ischemic stroke. Focal
      cerebral ischemia was induced by a transient (90 min) middle cerebral artery
      occlusion (MCAO). Animals were then subdivided into two groups and injected
      intravenously (i.v.) 6 hours post-MCAO with either 1 mg/kg PNU-120596 (treated
      group) or vehicle only (untreated group). Measurements of cerebral infarct
      volumes and neurological behavioral tests were performed 24 hrs post-MCAO. PNU
      120596 significantly reduced cerebral infarct volume and improved neurological
      function as evidenced by the results of Bederson, rolling cylinder and ladder
      rung walking tests. These results forecast a high therapeutic potential for PAMs
      II as effective recruiters and activators of endogenous alpha7 nAChR-dependent
      cholinergic pathways to reduce brain injury and improve neurological function
      after cerebral ischemic stroke. 

PMID- 23951361
TI  - Adhesion to carbon nanotube conductive scaffolds forces action-potential
      appearance in immature rat spinal neurons.
AB  - In the last decade, carbon nanotube growth substrates have been used to
      investigate neurons and neuronal networks formation in vitro when guided by
      artificial nano-scaled cues. Besides, nanotube-based interfaces are being
      developed, such as prosthesis for monitoring brain activity. We recently
      described how carbon nanotube substrates alter the electrophysiological and
      synaptic responses of hippocampal neurons in culture. This observation
      highlighted the exceptional ability of this material in interfering with nerve
      tissue growth. Here we test the hypothesis that carbon nanotube scaffolds promote
      the development of immature neurons isolated from the neonatal rat spinal cord,
      and maintained in vitro. To address this issue we performed electrophysiological
      studies associated to gene expression analysis. Our results indicate that spinal
      neurons plated on electro-conductive carbon nanotubes show a facilitated
      development. Spinal neurons anticipate the expression of functional markers of
      maturation, such as the generation of voltage dependent currents or action
      potentials. These changes are accompanied by a selective modulation of gene
      expression, involving neuronal and non-neuronal components. Our microarray
      experiments suggest that carbon nanotube platforms trigger reparative activities
      involving microglia, in the absence of reactive gliosis. Hence, future tissue
      scaffolds blended with conductive nanotubes may be exploited to promote cell
      differentiation and reparative pathways in neural regeneration strategies. 

PMID- 23951363
TI  - Clustered basic amino acids of the small sendai virus C protein Y1 are critical
      to its RAN GTPase-mediated nuclear localization.
AB  - The Sendai virus (SeV) C proteins are shown to exert multiple functions during
      the course of infection. Perhaps reflecting their many functions, they occur at
      multiple sites of the cell. In this study, we focused on the nuclear-localizing
      ability of the smaller C protein, Y1, and found that this translocation is
      mediated by Ran GTPase but not by passive diffusion, and that basic residues
      within the 149-157 amino acid region are critical for that. The mechanism of
      inhibition of interferon (IFN)-signaling seemed to differ between the C and Y1
      proteins, since deletion of 12 C-terminal amino acids resulted in a loss of the
      function for the C but not for the Y1 protein. The ability of Y1 mutants to
      inhibit IFN-alpha-induced, ISRE-driven expression of a reporter gene almost
      paralleled with that to localize in the nucleus. These results suggest that
      nuclear localization of the Y1 protein might be important for the inhibitory
      effect on type-I IFN-stimulated gene expression. 

PMID- 23951362
TI  - Switching tenofovir/emtricitabine plus lopinavir/r to raltegravir plus
      Darunavir/r in patients with suppressed viral load did not result in improvement
      of renal function but could sustain viral suppression: a randomized multicenter
      trial.
AB  - BACKGROUND: Whether tenofovir nephrotoxicity is reversible after its withdrawal
      is unknown. Furthermore, there are no data on the viral efficacy of raltegravir
      (RAL) plus ritonavir-boosted Darunavir (DRV/r) in patients with suppressed viral
      load. METHODS: This multicenter, randomized trial compared renal function and
      viral efficacy in patients with suppressed viral load treated with RAL+DRV/r and
      ritonavir-boosted lopinavir (LPV/r) plus tenofovir/emtricitabine (TVD), who had
      been previously on LPV/r+TVD. The primary endpoint was the proportion of patients
      with >10% improvement in estimated glomerular filtration rate (eGFR) at 48 weeks
      calculated with Cockcroft-Gault equation. RESULTS: 58 randomized and treatment
      exposed patients were analyzed (28 on RAL+DRV/r and 30 on LPV/r+TVD). Greater
      than 10% improvement in eGFR was noted in 6 (25%) out of 24 with RAL+DRV/r and 3
      (11%) of 28 with LPV/r+TVD, and the difference was not statistically significant
      (p=0.272, 95% CI -0.067 to 0.354). Sensitivity analyses using three other
      equations for eGFR showed the same results. Urinary beta2 microglobulin, a
      sensitive marker of tenofovir tubulopathy, significantly improved with RAL+DRV/r
      than with LPV/r+TVD (-271 versus -64 ug/gCr, p=0.026). Per protocol analysis
      showed that the HIV-RNA was <50 copies/mL at week 48 in all patients of both arms
      (24 in RAL+DRV and 29 in LPV/r+TVD). CONCLUSIONS: Switching LPV/r+TVD to
      RAL+DRV/r did not significantly increase the proportion of patients who showed
      >10% improvement in renal function among those with relatively preserved eGFR.
      However, the switch improved urinary beta2 microglobulin, suggesting that
      discontinuation of TDF might be beneficial in the long-term. RAL+DRV/r showed
      favorable viral efficacy in patients with suppressed viral load. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01294761
      http://clinicaltrials.gov/ct2/show/NCT01294761?term=SPARE&rank=2, Umin Clinical
      Trials Registry UMIN000005116 http://upload.umin.ac.jp/cgi-open
      bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000006083&langu
      ge=J).

PMID- 23951364
TI  - The mechanism of antifungal action of a new polyene macrolide antibiotic
      antifungalmycin 702 from Streptomyces padanus JAU4234 on the rice sheath blight
      pathogen Rhizoctonia solani.
AB  - Antifungalmycin 702, a new polyene macrolide antibiotic produced by
      Streptomycespadanus JAU4234, has a broad antifungal activity and may have
      potential future agricultural and/or clinical applications. However, the
      mechanism of antifungal action of antifungalmycin 702 remains unknown.
      Antifungalmycin 702 strongly inhibited mycelial growth and sclerotia
      formation/germination of Rhizoctonia solani. When treated with antifungalmycin
      702, the hyphae morphology of R. solani became more irregular. The membrane and
      the cellular organelles were disrupted and there were many vacuoles in the
      cellular space. The lesion in the plasma membrane was detected through the
      increase of membrane permeability, lipid peroxidation and leakage of cell
      constituents. In summary, antifungalmycin 702 may exert its antifungal activity
      against R. solani by changing the structure of cell membranes and the
      cytoskeleton and interacting with the organelles. 

PMID- 23951365
TI  - Hot or not: the effects of exogenous testosterone on female attractiveness to
      male conspecifics in the budgerigar.
AB  - An increasing number of studies indicate that not only females but also males can
      be selective when choosing a mate. In species exhibiting male or mutual mate
      choice, females may benefit from being attractive. While male attractiveness is
      often positively influenced by higher plasma levels of the androgenic hormone
      testosterone, it has been shown that testosterone can masculinise female behavior
      and morphology in several bird species, potentially rendering them less
      attractive. In this study, we investigated whether female budgerigars,
      Melopsittacusundulatus, suffer from increased plasma testosterone levels through
      a negative effect on their attractiveness to males. We experimentally increased
      plasma testosterone levels in testosterone-treated females (T-females) compared
      to controls (C-females) and allowed males to choose between a T- and a C-female
      in a two-way choice situation. Although testosterone treatment significantly
      affected female behavioral and morphological characteristics, males did not show
      a significant difference in preference between T- and C-females. These results
      suggest that experimentally increasing testosterone levels in females does not
      appear to influence male preference during initial mate choice. Our findings
      indicate that selection for higher levels of testosterone in male budgerigars is
      probably not constrained by a correlated response to selection causing negative
      effects on female attractiveness during initial mate choice. Evaluating whether
      or not a potential constraint may arise from negative testosterone-induced
      effects on other fitness related traits in females requires further work. 

PMID- 23951367
TI  - Taenia solium cysticercosis: the case of Cuba.

PMID- 23951366
TI  - Application of artificial neural networks to investigate one-carbon metabolism in
      Alzheimer's disease and healthy matched individuals.
AB  - Folate metabolism, also known as one-carbon metabolism, is required for several
      cellular processes including DNA synthesis, repair and methylation. Impairments
      of this pathway have been often linked to Alzheimer's disease (AD). In addition,
      increasing evidence from large scale case-control studies, genome-wide
      association studies, and meta-analyses of the literature suggest that
      polymorphisms of genes involved in one-carbon metabolism influence the levels of
      folate, homocysteine and vitamin B12, and might be among AD risk factors. We
      analyzed a dataset of 30 genetic and biochemical variables (folate, homocysteine,
      vitamin B12, and 27 genotypes generated by nine common biallelic polymorphisms of
      genes involved in folate metabolism) obtained from 40 late-onset AD patients and
      40 matched controls to assess the predictive capacity of Artificial Neural
      Networks (ANNs) in distinguish consistently these two different conditions and to
      identify the variables expressing the maximal amount of relevant information to
      the condition of being affected by dementia of Alzheimer's type. Moreover, we
      constructed a semantic connectivity map to offer some insight regarding the
      complex biological connections among the studied variables and the two conditions
      (being AD or control). TWIST system, an evolutionary algorithm able to remove
      redundant and noisy information from complex data sets, selected 16 variables
      that allowed specialized ANNs to discriminate between AD and control subjects
      with over 90% accuracy. The semantic connectivity map provided important
      information on the complex biological connections among one-carbon metabolic
      variables highlighting those most closely linked to the AD condition. 

PMID- 23951368
TI  - Evaluation of a typhoid/paratyphoid diagnostic assay (TPTest) detecting anti
      Salmonella IgA in secretions of peripheral blood lymphocytes in patients in
      Dhaka, Bangladesh.
AB  - BACKGROUND: Rapid and reliable diagnostic assays for enteric (typhoid and
      paratyphoid) fever are urgently needed. We report the characterization of novel
      approach utilizing lymphocyte secretions, for diagnosing patients with enteric
      fever by the TPTest procedure. METHODOLOGY: TPTest detects Salmonella-specific
      IgA responses in lymphocyte culture supernatant. We utilized TPTest in patients
      with suspected enteric fever, patients with other illnesses, and healthy
      controls. We also evaluated simplified modifications of TPTest for adaptation in
      laboratories with limited facilities and equipment. PRINCIPAL FINDINGS: TPTest
      was positive in 39 (27 typhoid and 12 paratyphoid A) patients confirmed by blood
      culture and was negative in 74 healthy individuals. Among 32 individuals with
      other illnesses, 29 were negative by TPTest. Of 204 individuals with suspected
      enteric fever who were negative by blood culture, 44 were positive by TPTest and
      the patients were clinically indistinguishable from patients with confirmed
      bacteremia, except they were more likely to be under 5 years of age. We evaluated
      simplifications in TPTest, including showing that lymphocytes could be recovered
      using lysis buffer or buffy coat method as opposed to centrifugation, that
      incubation of cells at 37 degrees C did not require supplemental CO2, and that
      results were available for majority of samples within 24 hours. Positive results
      by TPTest are transient and revert to negative during convalescence, supporting
      use of the test in endemic areas. The results can also be read using immunodot
      blot approach as opposed to ELISA. Since no true gold standard currently exists,
      we used a number of definitions of true positives and negatives. TPTest had
      sensitivity of 100% compared to blood culture, and specificity that ranged from
      78-97% (73-100, 95% CI), depending on definition of true negative. CONCLUSION:
      The TPTest is useful for identification of patients with enteric fever in an
      endemic area, and additional development of simplified TPTest is warranted.

PMID- 23951370
TI  - Fatal dengue in patients with sickle cell disease or sickle cell anemia in
      Curacao: two case reports.

PMID- 23951369
TI  - Toward the global control of human scabies: introducing the International
      Alliance for the Control of Scabies.

PMID- 23951371
TI  - Addressing ethical, social, and cultural issues in global health research.

PMID- 23951372
TI  - Imported amoebic liver abscess in France.
AB  - BACKGROUND: Worldwide, amoebic liver abscess (ALA) can be found in individuals in
      non-endemic areas, especially in foreign-born travelers. METHODS: We performed a
      retrospective analysis of ALA in patients admitted to French hospitals between
      2002 and 2006. We compared imported ALA cases in European and foreign-born
      patients and assessed the factors associated with abscess size using a logistic
      regression model. RESULTS: We investigated 90 ALA cases. Patient median age was
      41. The male:female ratio was 3.5:1. We were able to determine the origin for 75
      patients: 38 were European-born and 37 foreign-born. With respect to clinical
      characteristics, no significant difference was observed between European and
      foreign-born patients except a longer lag time between the return to France after
      traveling abroad and the onset of symptoms for foreign-born. Factors associated
      with an abscess size of more than 69 mm were being male (OR = 11.25, p<0.01),
      aged more than 41 years old (OR = 3.63, p = 0.02) and being an immigrant (OR =
      11.56, p = 0.03). Percutaneous aspiration was not based on initial abscess size
      but was carried out significantly more often on patients who were admitted to
      surgical units (OR = 10, p<0.01). The median time to abscess disappearance for 24
      ALA was 7.5 months. CONCLUSIONS/SIGNIFICANCE: In this study on imported ALA was
      one of the largest worldwide in terms of the number of cases included males,
      older patients and foreign-born patients presented with larger abscesses,
      suggesting that hormonal and immunological factors may be involved in ALA
      physiopathology. The long lag time before developing ALA after returning to a non
      endemic area must be highlighted to clinicians so that they will consider
      Entamoeba histolytica as a possible pathogen of liver abscesses more often.

PMID- 23951373
TI  - The effect of vaccination coverage and climate on Japanese encephalitis in
      Sarawak, Malaysia.
AB  - BACKGROUND: Japanese encephalitis (JE) is the leading cause of viral encephalitis
      across Asia with approximately 70,000 cases a year and 10,000 to 15,000 deaths.
      Because JE incidence varies widely over time, partly due to inter-annual climate
      variability effects on mosquito vector abundance, it becomes more complex to
      assess the effects of a vaccination programme since more or less climatically
      favourable years could also contribute to a change in incidence post-vaccination.
      Therefore, the objective of this study was to quantify vaccination effect on
      confirmed Japanese encephalitis (JE) cases in Sarawak, Malaysia after controlling
      for climate variability to better understand temporal dynamics of JE virus
      transmission and control. METHODOLOGY/PRINCIPAL FINDINGS: Monthly data on
      serologically confirmed JE cases were acquired from Sibu Hospital in Sarawak from
      1997 to 2006. JE vaccine coverage (non-vaccine years vs. vaccine years) and
      meteorological predictor variables, including temperature, rainfall and the
      Southern Oscillation index (SOI) were tested for their association with JE cases
      using Poisson time series analysis and controlling for seasonality and long-term
      trend. Over the 10-years surveillance period, 133 confirmed JE cases were
      identified. There was an estimated 61% reduction in JE risk after the
      introduction of vaccination, when no account is taken of the effects of climate.
      This reduction is only approximately 45% when the effects of inter-annual
      variability in climate are controlled for in the model. The Poisson model
      indicated that rainfall (lag 1-month), minimum temperature (lag 6-months) and SOI
      (lag 6-months) were positively associated with JE cases.
      CONCLUSIONS/SIGNIFICANCE: This study provides the first improved estimate of JE
      reduction through vaccination by taking account of climate inter-annual
      variability. Our analysis confirms that vaccination has substantially reduced JE
      risk in Sarawak but this benefit may be overestimated if climate effects are
      ignored.

PMID- 23951374
TI  - Molecular surveillance of dengue in Semarang, Indonesia revealed the circulation
      of an old genotype of dengue virus serotype-1.
AB  - Dengue disease is currently a major health problem in Indonesia and affects all
      provinces in the country, including Semarang Municipality, Central Java province.
      While dengue is endemic in this region, only limited data on the disease
      epidemiology is available. To understand the dynamics of dengue in Semarang, we
      conducted clinical, virological, and demographical surveillance of dengue in
      Semarang and its surrounding regions in 2012. Dengue cases were detected in both
      urban and rural areas located in various geographical features, including the
      coastal and highland areas. During an eight months' study, a total of 120 febrile
      patients were recruited, of which 66 were serologically confirmed for dengue
      infection using IgG/IgM ELISA and/or NS1 tests. The cases occurred both in dry
      and wet seasons. Majority of patients were under 10 years old. Most patients were
      diagnosed as dengue hemorrhagic fever, followed by dengue shock syndrome and
      dengue fever. Serotyping was performed in 31 patients, and we observed the co
      circulation of all four dengue virus (DENV) serotypes. When the serotypes were
      correlated with the severity of the disease, no direct correlation was observed.
      Phylogenetic analysis of DENV based on Envelope gene sequence revealed the
      circulation of DENV-2 Cosmopolitan genotype and DENV-3 Genotype I. A striking
      finding was observed for DENV-1, in which we found the co-circulation of Genotype
      I with an old Genotype II. The Genotype II was represented by a virus strain that
      has a very slow mutation rate and is very closely related to the DENV strain from
      Thailand, isolated in 1964 and never reported in other countries in the last
      three decades. Moreover, this virus was discovered in a cool highland area with
      an elevation of 1,001 meters above the sea level. The discovery of this old DENV
      strain may suggest the silent circulation of old virus strains in Indonesia. 

PMID- 23951375
TI  - Culling dogs in scenarios of imperfect control: realistic impact on the
      prevalence of canine visceral leishmaniasis.
AB  - BACKGROUND: Visceral leishmaniasis belongs to the list of neglected tropical
      diseases and is considered a public health problem worldwide. Spatial correlation
      between the occurrence of the disease in humans and high rates of canine
      infection suggests that in the presence of the vector, canine visceral
      leishmaniasis is the key factor for triggering transmission to humans. Despite
      the control strategies implemented, such as the sacrifice of infected dogs being
      put down, the incidence of American visceral leishmaniasis remains high in many
      Latin American countries. METHODOLOGY/PRINCIPAL FINDINGS: Mathematical models
      were developed to describe the transmission dynamics of canine leishmaniasis and
      its control by culling. Using these models, imperfect control scenarios were
      implemented to verify the possible factors which alter the effectiveness of
      controlling this disease in practice. CONCLUSIONS/SIGNIFICANCE: A long-term
      continuous program targeting both asymptomatic and symptomatic dogs should be
      effective in controlling canine leishmaniasis in areas of low to moderate
      transmission (R0 up to 1.4). However, the indiscriminate sacrifice of
      asymptomatic dogs with positive diagnosis may jeopardize the effectiveness of the
      control program, if tests with low specificity are used, increasing the chance of
      generating outrage in the population, and leading to lower adherence to the
      program. Therefore, culling must be planned accurately and implemented
      responsibly and never as a mechanical measure in large scale. In areas with
      higher transmission, culling alone is not an effective control strategy.

PMID- 23951376
TI  - Inter-epidemic transmission of Rift Valley fever in livestock in the Kilombero
      River Valley, Tanzania: a cross-sectional survey.
AB  - BACKGROUND: In recent years, evidence of Rift Valley fever (RVF) transmission
      during inter-epidemic periods in parts of Africa has increasingly been reported.
      The inter-epidemic transmissions generally pass undetected where there is no
      surveillance in the livestock or human populations. We studied the presence of
      and the determinants for inter-epidemic RVF transmission in an area experiencing
      annual flooding in southern Tanzania. METHODOLOGY: A cross-sectional sero-survey
      was conducted in randomly selected cattle, sheep and goats in the Kilombero river
      valley from May to August 2011, approximately four years after the 2006/07 RVF
      outbreak in Tanzania. The exposure status to RVF virus (RVFV) was determined
      using two commercial ELISA kits, detecting IgM and IgG antibodies in serum.
      Information about determinants was obtained through structured interviews with
      herd owners. FINDINGS: An overall seroprevalence of 11.3% (n = 1680) was
      recorded; 5.5% in animals born after the 2006/07 RVF outbreak and 22.7% in
      animals present during the outbreak. There was a linear increase in prevalence in
      the post-epidemic annual cohorts. Nine inhibition-ELISA positive samples were
      also positive for RVFV IgM antibodies indicating a recent infection. The spatial
      distribution of seroprevalence exhibited a few hotspots. The sex difference in
      seroprevalence in animals born after the previous epidemic was not significant
      (6.1% vs. 4.6% for females and males respectively, p = 0.158) whereas it was
      significant in animals present during the outbreak (26.0% vs. 7.8% for females
      and males respectively, p<0.001). Animals living >15 km from the flood plain were
      more likely to have antibodies than those living <5 km (OR 1.92; 95% CI 1.04
      3.56). Species, breed, herd composition, grazing practices and altitude were not
      associated with seropositivity. CONCLUSION: These findings indicate post-epidemic
      transmission of RVFV in the study area. The linear increase in seroprevalence in
      the post-epidemic annual cohorts implies a constant exposure and presence of
      active foci transmission preceding the survey.

PMID- 23951377
TI  - Symptomatic versus inapparent outcome in repeat dengue virus infections is
      influenced by the time interval between infections and study year.
AB  - Four dengue virus serotypes (DENV1-4) circulate globally, causing more human
      illness than any other arthropod-borne virus. Dengue can present as a range of
      clinical manifestations from undifferentiated fever to Dengue Fever to severe,
      life-threatening syndromes. However, most DENV infections are inapparent. Yet,
      little is known about determinants of inapparent versus symptomatic DENV
      infection outcome. Here, we analyzed over 2,000 DENV infections from 2004 to 2011
      in a prospective pediatric cohort study in Managua, Nicaragua. Symptomatic cases
      were captured at the study health center, and paired healthy annual samples were
      examined on a yearly basis using serological methods to identify inapparent DENV
      infections. Overall, inapparent and symptomatic DENV infections were equally
      distributed by sex. The mean age of infection was 1.2 years higher for
      symptomatic DENV infections as compared to inapparent infections. Although
      inapparent versus symptomatic outcome did not differ by infection number (first,
      second or third/post-second DENV infections), substantial variation in the
      proportion of symptomatic DENV infections among all DENV infections was observed
      across study years. In participants with repeat DENV infections, the time
      interval between a first inapparent DENV infection and a second inapparent
      infection was significantly shorter than the interval between a first inapparent
      and a second symptomatic infection. This difference was not observed in
      subsequent infections. This result was confirmed using two different serological
      techniques that measure total anti-DENV antibodies and serotype-specific
      neutralizing antibodies, respectively. Taken together, these findings show that,
      in this study, age, study year and time interval between consecutive DENV
      infections influence inapparent versus symptomatic infection outcome, while sex
      and infection number had no significant effect. Moreover, these results suggest
      that the window of cross-protection induced by a first infection with DENV
      against a second symptomatic infection is approximately 2 years. These findings
      are important for modeling dengue epidemics and development of vaccines. 

PMID- 23951378
TI  - The geographical distribution and burden of trachoma in Africa.
AB  - BACKGROUND: There remains a lack of epidemiological data on the geographical
      distribution of trachoma to support global mapping and scale up of interventions
      for the elimination of trachoma. The Global Atlas of Trachoma (GAT) was launched
      in 2011 to address these needs and provide standardised, updated and accessible
      maps. This paper uses data included in the GAT to describe the geographical
      distribution and burden of trachoma in Africa. METHODS: Data assembly used
      structured searches of published and unpublished literature to identify cross
      sectional epidemiological data on the burden of trachoma since 1980. Survey data
      were abstracted into a standardised database and mapped using geographical
      information systems (GIS) software. The characteristics of all surveys were
      summarized by country according to data source, time period, and survey
      methodology. Estimates of the current population at risk were calculated for each
      country and stratified by endemicity class. RESULTS: At the time of writing, 1342
      records are included in the database representing surveys conducted between 1985
      and 2012. These data were provided by direct contact with national control
      programmes and academic researchers (67%), peer-reviewed publications (17%) and
      unpublished reports or theses (16%). Prevalence data on active trachoma are
      available in 29 of the 33 countries in Africa classified as endemic for trachoma,
      and 1095 (20.6%) districts have representative data collected through population
      based prevalence surveys. The highest prevalence of active trachoma and
      trichiasis remains in the Sahel area of West Africa and Savannah areas of East
      and Central Africa and an estimated 129.4 million people live in areas of Africa
      confirmed to be trachoma endemic. CONCLUSION: The Global Atlas of Trachoma
      provides the most contemporary and comprehensive summary of the burden of
      trachoma within Africa. The GAT highlights where future mapping is required and
      provides an important planning tool for scale-up and surveillance of trachoma
      control.

PMID- 23951379
TI  - An epidemic of dengue-1 in a remote village in rural Laos.
AB  - In the Lao PDR (Laos), urban dengue is an increasingly recognised public health
      problem. We describe a dengue-1 virus outbreak in a rural northwestern Lao forest
      village during the cool season of 2008. The isolated strain was genotypically
      "endemic" and not "sylvatic," belonging to the genotype 1, Asia 3 clade.
      Phylogenetic analyses of 37 other dengue-1 sequences from diverse areas of Laos
      between 2007 and 2010 showed that the geographic distribution of some strains
      remained focal overtime while others were dispersed throughout the country.
      Evidence that dengue viruses have broad circulation in the region, crossing
      country borders, was also obtained. Whether the outbreak arose from dengue
      importation from an urban centre into a dengue-naive community or crossed into
      the village from a forest cycle is unknown. More epidemiological and
      entomological investigations are required to understand dengue epidemiology and
      the importance of rural and forest dengue dynamics in Laos. 

PMID- 23951381
TI  - Wolbachia-associated bacterial protection in the mosquito Aedes aegypti.
AB  - BACKGROUND: Wolbachia infections confer protection for their insect hosts against
      a range of pathogens including bacteria, viruses, nematodes and the malaria
      parasite. A single mechanism that might explain this broad-based pathogen
      protection is immune priming, in which the presence of the symbiont upregulates
      the basal immune response, preparing the insect to defend against subsequent
      pathogen infection. A study that compared natural Wolbachia infections in
      Drosophila melanogaster with the mosquito vector Aedes aegypti artificially
      transinfected with the same strains has suggested that innate immune priming may
      only occur in recent host-Wolbachia associations. This same study also revealed
      that while immune priming may play a role in viral protection it cannot explain
      the entirety of the effect. METHODOLOGY/FINDINGS: Here we assess whether the
      level of innate immune priming induced by different Wolbachia strains in A.
      aegypti is correlated with the degree of protection conferred against bacterial
      pathogens. We show that Wolbachia strains wMel and wMelPop, currently being
      tested for field release for dengue biocontrol, differ in their protective
      abilities. The wMelPop strain provides stronger, more broad-based protection than
      wMel, and this is likely explained by both the higher induction of immune gene
      expression and the strain-specific activation of particular genes. We also show
      that Wolbachia densities themselves decline during pathogen infection, likely as
      a result of the immune induction. CONCLUSIONS/SIGNIFICANCE: This work shows a
      correlation between innate immune priming and bacterial protection phenotypes.
      The ability of the Toll pathway, melanisation and antimicrobial peptides to
      enhance viral protection or to provide the basis of malaria protection should be
      further explored in the context of this two-strain comparison. This work raises
      the questions of whether Wolbachia may improve the ability of wild mosquitoes to
      survive pathogen infection or alter the natural composition of gut flora, and
      thus have broader consequences for host fitness.

PMID- 23951380
TI  - Tracing the tiger: population genetics provides valuable insights into the Aedes
      (Stegomyia) albopictus invasion of the Australasian Region.
AB  - BACKGROUND: The range of the Asian tiger mosquito Aedes albopictus is expanding
      globally, raising the threat of emerging and re-emerging arbovirus transmission
      risks including dengue and chikungunya. Its detection in Papua New Guinea's (PNG)
      southern Fly River coastal region in 1988 and 1992 placed it 150 km from mainland
      Australia. However, it was not until 12 years later that it appeared on the
      Torres Strait Islands. We hypothesized that the extant PNG population expanded
      into the Torres Straits as an indirect effect of drought-proofing the southern
      Fly River coastal villages in response to El Nino-driven climate variability in
      the region (via the rollout of rainwater tanks and water storage containers).
      METHODOLOGY/PRINCIPAL FINDINGS: Examination of the mosquito's mitochondrial DNA
      cytochrome oxidase I (COI) sequences and 13 novel nuclear microsatellites
      revealed evidence of substantial intermixing between PNG's southern Fly region
      and Torres Strait Island populations essentially compromising any island
      eradication attempts due to potential of reintroduction. However, two genetically
      distinct populations were identified in this region comprising the historically
      extant PNG populations and the exotic introduced population. Both COI sequence
      data and microsatellites showed the introduced population to have genetic
      affinities to populations from Timor Leste and Jakarta in the Indonesian region.
      CONCLUSIONS/SIGNIFICANCE: The Ae. albopictus invasion into the Australian region
      was not a range expansion out of PNG as suspected, but founded by other,
      genetically distinct population(s), with strong genetic affinities to populations
      sampled from the Indonesian region. We now suspect that the introduction of Ae.
      albopictus into the Australian region was driven by widespread illegal fishing
      activity originating from the Indonesian region during this period. Human sea
      traffic is apparently shuttling this mosquito between islands in the Torres
      Strait and the southern PNG mainland and this extensive movement may well
      compromise Ae. albopictus eradication attempts in this region.

PMID- 23951382
TI  - Induction of mouse melioidosis with meningitis by CD11b+ phagocytic cells
      harboring intracellular B. pseudomallei as a Trojan horse.
AB  - BACKGROUND: Approximately 3-5% of patients with melioidosis manifest CNS
      symptoms; however, the clinical data regarding neurological melioidosis are
      limited. METHODS AND FINDINGS: We established a mouse model of melioidosis with
      meningitis characterized by neutrophil infiltration into the meninges
      histologically and B. pseudomallei in the cerebrospinal fluid (CSF) by
      bacteriological culturing methods. As the disease progresses, the bacteria
      successively colonize the spleen, liver, bone marrow (BM) and brain and invade
      splenic and BM cells by days 2 and 6 post-infection, respectively. The
      predominant cell types intracellularly infected with B. pseudomallei were splenic
      and BM CD11b(+) populations. The CD11b(+)Ly6C(high) inflamed monocytes,
      CD11b(+)Ly6C(low) resident monocytes, CD11b(+)Ly6G(+) neutrophils,
      CD11b(+)F4/80(+) macrophages and CD11b(+)CD19(+) B cells were expanded in the
      spleen and BM during the progression of melioidosis. After adoptive transfer of
      CD11b populations harboring B. pseudomallei, the infected CD11b(+) cells induced
      bacterial colonization in the brain, whereas CD11b(-) cells only partially
      induced colonization; extracellular (free) B. pseudomallei were unable to
      colonize the brain. CD62L (selectin) was absent on splenic CD11b(+) cells on day
      4 but was expressed on day 10 post-infection. Adoptive transfer of CD11b(+) cells
      expressing CD62L (harvested on day 10 post-infection) resulted in meningitis in
      the recipients, but transfer of CD11b(+) CD62L-negative cells did not.
      CONCLUSIONS/SIGNIFICANCE: We suggest that B. pseudomallei-infected CD11b(+)
      selectin-expressing cells act as a Trojan horse and are able to transmigrate
      across endothelial cells, resulting in melioidosis with meningitis.

PMID- 23951383
TI  - Innate immune responses and antioxidant/oxidant imbalance are major determinants
      of human Chagas disease.
AB  - BACKGROUND: We investigated the pathological and diagnostic role of selected
      markers of inflammation, oxidant/antioxidant status, and cellular injury in human
      Chagas disease. METHODS: Seropositive/chagasic subjects characterized as
      clinically-symptomatic or clinically-asymptomatic (n = 116), seronegative/cardiac
      subjects (n = 102), and seronegative/healthy subjects (n = 45) were analyzed for
      peripheral blood biomarkers. RESULTS: Seropositive/chagasic subjects exhibited an
      increase in sera or plasma levels of myeloperoxidase (MPO, 2.8-fold), advanced
      oxidation protein products (AOPP, 56%), nitrite (5.7-fold), lipid peroxides (LPO,
      12-17-fold) and malondialdehyde (MDA, 4-6-fold); and a decline in superoxide
      dismutase (SOD, 52%) and glutathione (GSH, 75%) contents. Correlation analysis
      identified a significant (p<0.001) linear relationship between inflammatory
      markers (AOPP/nitrite: r = 0.877), inflammation and antioxidant/oxidant status
      (AOPP/glutathione peroxidase (GPX): r = 0.902, AOPP/GSH: r = 0.806, Nitrite/GPX:
      0.773, Nitrite/LPO: 0.805, MDA/MPO: 0.718), and antioxidant/oxidant levels
      (GPX/MDA: r = 0.768) in chagasic subjects. Of these, MPO, LPO and nitrite
      biomarkers were highly specific and sensitive for distinguishing
      seropositive/chagasic subjects from seronegative/healthy controls (p<0.001,
      training and fitting AUC/ROC >0.95). The MPO (r = 0.664) and LPO (r = 0.841)
      levels were also correlated with clinical disease state in chagasic subjects
      (p<0.001). Seronegative/cardiac subjects exhibited up to 77% decline in SOD, 3-5
      fold increase in LPO and glutamate pyruvate transaminase (GPT) levels, and
      statistically insignificant change in MPO, AOPP, MDA, GPX, GSH, and creatine
      kinase (CK) levels. CONCLUSIONS: The interlinked effects of innate immune
      responses and antioxidant/oxidant imbalance are major determinants of human
      Chagas disease. The MPO, LPO and nitrite are excellent biomarkers for diagnosing
      seropositive/chagasic subjects, and MPO and LPO levels have potential utility in
      identifying clinical severity of Chagas disease.

PMID- 23951385
TI  - Soil-transmitted helminth infections and nutritional status in school-age
      children from rural communities in Honduras.
AB  - BACKGROUND: Soil-transmitted helminth (STH) infections are endemic in Honduras
      and efforts are underway to decrease their transmission. However, current
      evidence is lacking in regards to their prevalence, intensity and their impact on
      children's health. OBJECTIVES: To evaluate the prevalence and intensity of STH
      infections and their association with nutritional status in a sample of Honduran
      children. METHODOLOGY: A cross-sectional study was done among school-age children
      residing in rural communities in Honduras, in 2011. Demographic data was
      obtained, hemoglobin and protein concentrations were determined in blood samples
      and STH infections investigated in single-stool samples by Kato-Katz.
      Anthropometric measurements were taken to calculate height-for-age (HAZ), BMI-for
      age (BAZ) and weight-for-age (WAZ) to determine stunting, thinness and
      underweight, respectively. RESULTS: Among 320 children studied (48% girls, aged 7
      14 years, mean 9.76 +/- 1.4) an overall STH prevalence of 72.5% was found.
      Children >10 years of age were generally more infected than 7-10 year-olds (p =
      0.015). Prevalence was 30%, 67% and 16% for Ascaris, Trichuris and hookworms,
      respectively. Moderate-to-heavy infections as well as polyparasitism were common
      among the infected children (36% and 44%, respectively). Polyparasitism was four
      times more likely to occur in children attending schools with absent or annual
      deworming schedules than in pupils attending schools deworming twice a year
      (p<0.001). Stunting was observed in 5.6% of children and it was associated with
      increasing age. Also, 2.2% of studied children were thin, 1.3% underweight and
      2.2% had anemia. Moderate-to-heavy infections and polyparasitism were
      significantly associated with decreased values in WAZ and marginally associated
      with decreased values in HAZ. CONCLUSIONS: STH infections remain a public health
      concern in Honduras and despite current efforts were highly prevalent in the
      studied community. The role of multiparasite STH infections in undermining
      children's nutritional status warrants more research.

PMID- 23951384
TI  - Identification and functional analysis of Trypanosoma cruzi genes that encode
      proteins of the glycosylphosphatidylinositol biosynthetic pathway.
AB  - BACKGROUND: Trypanosoma cruzi is a protist parasite that causes Chagas disease.
      Several proteins that are essential for parasite virulence and involved in host
      immune responses are anchored to the membrane through
      glycosylphosphatidylinositol (GPI) molecules. In addition, T. cruzi GPI anchors
      have immunostimulatory activities, including the ability to stimulate the
      synthesis of cytokines by innate immune cells. Therefore, T. cruzi genes related
      to GPI anchor biosynthesis constitute potential new targets for the development
      of better therapies against Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: In
      silico analysis of the T. cruzi genome resulted in the identification of 18 genes
      encoding proteins of the GPI biosynthetic pathway as well as the
      inositolphosphorylceramide (IPC) synthase gene. Expression of GFP fusions of some
      of these proteins in T. cruzi epimastigotes showed that they localize in the
      endoplasmic reticulum (ER). Expression analyses of two genes indicated that they
      are constitutively expressed in all stages of the parasite life cycle. T. cruzi
      genes TcDPM1, TcGPI10 and TcGPI12 complement conditional yeast mutants in GPI
      biosynthesis. Attempts to generate T. cruzi knockouts for three genes were
      unsuccessful, suggesting that GPI may be an essential component of the parasite.
      Regarding TcGPI8, which encodes the catalytic subunit of the transamidase
      complex, although we were able to generate single allele knockout mutants,
      attempts to disrupt both alleles failed, resulting instead in parasites that have
      undergone genomic recombination and maintained at least one active copy of the
      gene. CONCLUSIONS/SIGNIFICANCE: Analyses of T. cruzi sequences encoding
      components of the GPI biosynthetic pathway indicated that they are essential
      genes involved in key aspects of host-parasite interactions. Complementation
      assays of yeast mutants with these T. cruzi genes resulted in yeast cell lines
      that can now be employed in high throughput screenings of drugs against this
      parasite.

PMID- 23951386
TI  - Renal cell carcinoma in a setting of chronic lithium toxicity.
AB  - PATIENT: Female, 72 FINAL DIAGNOSIS: Renal cell carcinoma Symptoms: - MEDICATION:
      - Clinical Procedure: - Specialty: Oncology. OBJECTIVE: Challenging differential
      diagnosis. BACKGROUND: Lithium salts are widely used in the treatment of
      affective disorders of the bipolar type. Lithium is a nephrotoxic substance which
      can cause both acute and chronic renal disease, including cyst formation. Cysts
      appear to predispose the kidney to renal cell carcinoma. CASE REPORT: A case of
      renal cell carcinoma in a background of acquired cystic disease due to chronic
      lithium toxicity is described. CONCLUSIONS: Kidneys with multiple cysts are at
      risk of renal cell carcinoma. Although it is difficult to determine if long term
      Lithium use renal cell carcinoma, patients leads to the development of on long
      term lithium therapy should undergo regular renal function and imaging tests.

PMID- 23951387
TI  - Perspectives of gene combinations in phenotype presentation.
AB  - Cells exhibit a variety of phenotypes in different stages and diseases. Although
      several markers for cellular phenotypes have been identified, gene combinations
      denoting cellular phenotypes have not been completely elucidated. Recent advances
      in gene analysis have revealed that various gene expression patterns are observed
      in each cell species and status. In this review, the perspectives of gene
      combinations in cellular phenotype presentation are discussed. Gene expression
      profiles change during cellular processes, such as cell proliferation, cell
      differentiation, and cell death. In addition, epigenetic regulation increases the
      complexity of the gene expression profile. The role of gene combinations and
      panels of gene combinations in each cellular condition are also discussed. 

PMID- 23951388
TI  - Fifteen years of preclinical and clinical experiences about biotherapy treatment
      of lesions induced by accidental irradiation and radiotherapy.
AB  - High dose radiation exposures involving medical treatments or accidental
      irradiation may lead to extended damage to the irradiated tissue. Alleviation or
      even eradication of irradiation induced adverse events is therefore crucial.
      Because developments in cell therapy have brought some hope for the treatment of
      tissues damages induced by irradiation, the Institute for Radiation and Nuclear
      Safety contributed to establish the clinical guidelines for the management of
      accidentally irradiated victims and to provide the best supportive care to
      patients all over the world. In the past 15 years, we contributed to develop and
      test cell therapy for protection against radiation side effects in several animal
      models, and we proposed mechanisms to explain the benefit brought by this new
      therapeutic approach. We established the proof of concept that mesenchymal stem
      cells (MSCs) migrate to damaged tissues in the nonobese diabetic/severe combined
      immunodeficiency immunotolerant mice model and in non-human primate after
      radiation exposure. We showed that the intravenous injection of MSCs sustains
      hematopoiesis after total body irradiation, improves wound healing after
      radiodermatitis and protects gut function from irradiation damages. Thanks to a
      tight collaboration with clinicians from several French hospitals, we report
      successful treatments of therapeutic/accidental radiation damages in several
      victims with MSC infusions for hematopoiesis correction, radio-induced burns,
      gastrointestinal disorders and protection homeostatic functions of gut management
      after radio-therapy. 

PMID- 23951390
TI  - Air embolism complicating gastrointestinal endoscopy: A systematic review.
AB  - Gastrointestinal endoscopy has become an important modality for the diagnosis and
      treatment of various gastrointestinal disorders. One of its major advantages is
      that it is minimally invasive and has an excellent safety record. Nevertheless,
      some complications do occur, and endoscopists are well aware and prepared to deal
      with the commonly recognized ones including bleeding, perforation, infection, and
      adverse effects from the sedative medications. Air embolism is a very rare
      endoscopic complication but possesses the potential to be severe and fatal. It
      can present with cardiopulmonary instability and neurologic symptoms. The
      diagnosis may be difficult because of its clinical presentation, which can
      overlap with sedation-related cardiopulmonary problems or neurologic symptoms
      possibly attributed to an ischemic or hemorrhagic central nervous system event.
      Increased awareness is essential for prompt recognition of the air embolism,
      which can allow potentially life-saving therapy to be provided. Therefore, we
      wanted to review the risk factors, the clinical presentation, and the therapy of
      an air embolism from the perspective of the practicing endoscopist. 

PMID- 23951389
TI  - Epigenetics and chromatin plasticity in embryonic stem cells.
AB  - The study of embryonic stem cells is in the spotlight in many laboratories that
      study the structure and function of chromatin and epigenetic processes. The key
      properties of embryonic stem cells are their capacity for self-renewal and their
      pluripotency. Pluripotent stem cells are able to differentiate into the cells of
      all three germ layers, and because of this property they represent a promising
      therapeutic tool in the treatment of diseases such as Parkinson's disease and
      diabetes, or in the healing of lesions after heart attack. As the basic nuclear
      unit, chromatin is responsible for the regulation of the functional status of
      cells, including pluripotency and differentiation. Therefore, in this review we
      discuss the functional changes in chromatin during differentiation and the
      correlation between epigenetics events and the differentiation potential of
      embryonic stem cells. In particular we focus on post-translational histone
      modification, DNA methylation and the heterochromatin protein HP1 and its unique
      function in mouse and human embryonic stem cells. 

PMID- 23951391
TI  - Fetal radiation exposure: Is monitoring really needed?
AB  - The effect of fetal radiation during endoscopic retrograde
      cholangiopancreatography (ERCP) on pregnant women is a very interesting topic.
      Smith et al recently estimated the fetal radiation exposure in pregnant women
      undergoing ERCPs using thermoluminescent dosimeters (TLDs). The authors concluded
      that TLDs are unnecessary during ERCP with modified techniques. We believe that
      an extreme caution is needed in clinical practice before drawing such conclusions
      when they are not strongly supported by enough experimental evidence. Therefore,
      we recommend that fetal radiation exposure be monitored in clinical practice by
      using dosimeters, bearing in mind that all relevant techniques to control and
      minimize the exposure must be applied. 

PMID- 23951392
TI  - Training in endoscopic submucosal dissection.
AB  - Endoscopic submucosal dissection (ESD) represents an important advancement in the
      therapy of early neoplastic gastrointestinal lesions by providing higher en-bloc
      curative resection rate with lower recurrence compared to endoscopic mucosal
      resection (EMR) and by sparing the involved organ and protecting patient's
      quality of life. Despite these advantages ESD is associated with long procedure
      times and a higher rate of complications, making ESD a challenging procedure
      which requires advanced endoscopic skills. Thus, there has been a recognized need
      for structured training system for ESD to enhance trainee experience and, to
      reduce the risks of complications and inadequate treatment. ESD has a very flat
      learning curve. However, we do not have uniformly accepted benchmarks for
      competency. Nevertheless, it appears that, in Japan, more than 30 supervised
      gastric ESD procedures are required to achieve technical proficiency and minimize
      complications. A number of training algorithms have been proposed in Japan with
      the aim to standardize ESD training. These algorithms cannot be directly applied
      in the West due to substantial differences including the availability of highly
      qualified mentors, the type of pathology seen, choice of devices, and trainee's
      background. We propose a training algorithm for Western physicians which
      integrates both hands-on training courses, animal model work as well as visits to
      expert centers. No specific preceptor training programs have been yet developed
      but there is a consensus that these programs are important for permeation of ESD
      worldwide. 

PMID- 23951394
TI  - Prevalence and clinical features of colonic diverticulosis in a Middle Eastern
      population.
AB  - AIM: To determine the prevalence, location, associations and clinical features of
      colonic-diverticulosis and its role as a cause of lower-gastroenterology
      bleeding. METHODS: We retrospectively reviewed the medical records of 3649
      consecutive patients who underwent a colonoscopy for all indications between 2007
      and 2011 at King Khalid University Hospital, Riyadh, Saudi Arabia. The
      demographic data were collected retrospectively through the hospital's
      information system, electronic file system, endoscopic e-reports, and manual
      review of the files by two research assistants. The demographic information
      included the age, sex, comorbidities and indication for the colonoscopy. The
      association among colonic polyps, comorbidities and diverticular disease was also
      measured. RESULTS: A total of 270 patients out of 3649 were diagnosed with
      colonic diverticulosis, with a prevalence of 7.4%. The mean age was 60.82 years
      +/- 0.833, (range 12-110). Females comprised 38.89% (95%CI: 33-44.7) of the study
      population. The major symptoms were rectal bleeding in 33.6%, abdominal pain in
      19.3%, constipation in 12.8% and anemia in 6%. Diverticula were predominantly
      left-sided (sigmoid and descending colon) in 62%, right-sided in 13% and in
      multiple locations in 25%. There was an association between the presence of
      diverticulosis and adenomatous polyps (P-value < 0.001), hypertension (P-value <
      0.0001) and diabetes mellitus (P-value < 0.0016). Diverticular disease was the
      second most common cause of lower gastrointestinal bleeding, in 33.6% (95%CI:
      27.7-39.4), after internal hemorrhoids, in 44.6% (95%CI: 40.3-48.9). On
      multivariable logistic regression, hypertension (OR = 2.30; 95%CI: 1.29-4.10),
      rectal bleeding (OR = 2.57; 95%CI: 1.50-4.38), and per year increment in age (OR
      = 1.05; 95%CI: 1.03-1.07) were associated with diverticulosis but not with
      bleeding diverticular disease. LIMITATIONS: A small proportion of the patients
      included had colonoscopies performed as a screening test. CONCLUSION: Colonic
      diverticulosis was found to have a low prevalence, be predominantly left-sided
      and associated with adenomatous-polyps. Age, hypertension and rectal bleeding
      predict the presence of diverticular disease.

PMID- 23951393
TI  - Endoscopic approach to achalasia.
AB  - Achalasia is a primary esophageal motor disorder. The etiology is still unknown
      and therefore all treatment options are strictly palliative with the intention to
      weaken the lower esophageal sphincter (LES). Current established endoscopic
      therapeutic options include pneumatic dilation (PD) or botulinum toxin injection.
      Both treatment approaches have an excellent symptomatic short term effect, and
      lead to a reduction of LES pressure. However, the long term success of botulinum
      toxin (BT) injection is poor with symptom recurrence in more than 50% of the
      patients after 12 mo and in nearly 100% of the patients after 24 mo, which
      commonly requires repeat injections. In contrast, after a single PD 40%-60% of
      the patients remain asymptomatic for >= 10 years. Repeated on demand PD might
      become necessary and long term remission can be achieved with this approach in up
      to 90% of these patients. The main positive predictors for a symptomatic response
      to PD are an age > 40 years, a LES-pressure reduction to < 15 mmHg and/or an
      improved radiological esophageal clearance post-PD. However PD has a significant
      risk for esophageal perforation, which occurs in about 2%-3% of cases. In
      randomized, controlled studies BT injection was inferior to PD and surgical
      cardiomyotomy, whereas the efficacy of PD, in patients > 40 years, was nearly
      equivalent to surgery. A new promising technique might be peroral endoscopic
      myotomy, although long term results are needed and practicability as well as
      safety issues must be considered. Treatment with a temporary self expanding stent
      has been reported with favorable outcomes, but the data are all from one study
      group and must be confirmed by others before definite recommendations can be
      made. In addition to its use as a therapeutic tool, endoscopy also plays an
      important role in the diagnosis and surveillance of patients with achalasia. 

PMID- 23951395
TI  - Conservative management of small bowel perforation in Ehlers-Danlos syndrome type
      IV.
AB  - Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders
      caused by collagen synthesis defects. EDS type IV, or vascular EDS, is caused by
      loss-of-function mutations in the type III pro-collagen gene (COL3A1). Common
      complications of EDS type IV include gastrointestinal bleeding and bowel
      perforations, posing diagnostic and therapeutic dilemmas for both surgeons and
      gastroenterologists. Here, we describe a complicated case of EDS type IV in a 35
      year-old caucasian female who presented with overt gastrointestinal bleeding. The
      patient had a prior history of spontaneous colonic perforation, and an
      uncomplicated upper endoscopy was performed. A careful ileoscopy was terminated
      early due to tachycardia and severe abdominal pain, and a subsequent computed
      tomography scan confirmed the diagnosis of ileal perforation. The patient was
      managed conservatively, and demonstrated daily improvement. At the time of
      hospital discharge, no further episodes of gastrointestinal blood loss had
      occurred. This case highlights the benefit of conservative management for EDS
      patients with gastrointestinal hemorrhage. It is recommended that surgical
      treatment should be reserved for patients who fail conservative treatment or in
      cases of hemodynamic instability. Finally, this case demonstrates the necessity
      for a higher threshold of operative or endoscopic interventions in EDS type IV
      patients. 

PMID- 23951396
TI  - Endoscopic closure of a gastrocolic fistula using the over-the-scope-clip-system.
AB  - Gastrointestinal (GI) defects such as fistulas and leaks can be potentially
      closed endoscopically using hemoclips and loops. However, hemoclips may not allow
      for closure of large defects and they do not exert enough tensile force to keep
      fibrotic defects larger than 5 mm approximated. Herein we present a case of
      successful endoscopic closure of a gastrocolic fistula in a severely malnourished
      patient with complex post-surgical upper GI anatomy. We strongly believe that
      this device is a major breakthrough for the management of various types of
      discontinuity defects or fistulas. In addition, we show the usefulness of placing
      a direct jejunostomy using the double balloon enteroscopy (DBE) technique during
      the same procedure. The concept of providing direct jejunal feedings while
      allowing for upper gastrointestinal bowel rest to promote the healing of the
      minimally invasive endoscopic operation is novel. Thus, our case is unique and
      exemplifies the utility of minimally invasive endoscopic endoluminal surgery. 

PMID- 23951397
TI  - Malignant peritoneal mesothelioma presenting umbilical hernia and Sister Mary
      Joseph's nodule.
AB  - Malignant peritoneal mesothelioma is a rare aggressive tumor of the peritoneum.
      An increasing number of malignant mesothelioma cases have been reported in recent
      years. We report here a very rare case of malignant peritoneal mesothelioma with
      both umbilical hernia and umbilical metastasis which is also called Sister Mary
      Joseph's nodule. We performed laparoscopy which showed specific laparoscopic
      findings, and the pathological findings of the biopsy specimen led to the
      diagnosis. This case was associated with umbilical hernia which could be induced
      by massive ascites. A newly developed abdominal hernia should be noted as a
      primary symptom of malignant peritoneal mesothelioma, as shown in the present
      case. 

PMID- 23951398
TI  - Dilation of a severe bilioenteric or pancreatoenteric anastomotic stricture using
      a Soehendra Stent Retriever.
AB  - Bilioenteric or pancreatoenteric anastomotic strictures often occur after surgery
      for a pancreaticobiliary disorder. Therapeutic endoscopic retrograde
      cholangiopancreatography using balloon enteroscopy has been shown to be feasible
      and effective in patients with such strictures. However, when a benign
      anastomotic stricture is severe, a dilation catheter cannot pass through the
      stricture despite successful insertion of the guidewire. We report on the
      usefulness of the Soehendra Stent Retriever over a guidewire for dilating a
      severe bilioenteric or pancreatoenteric anastomotic stricture under short double
      balloon enteroscopy, in two patients with surgically altered anatomies. 

PMID- 23951399
TI  - Endoscopic management of Dieulafoy's lesion using Isoamyl-2-cyanoacrylate.
AB  - Dieulafoy's lesion (DL) is a rare but important cause of obscure gastrointestinal
      bleeding that may be overlooked during diagnostic endoscopy. Mortality rates are
      similar to those of other causes for gastrointestinal bleeding. Diagnosis by
      upper endoscopy is the modality of choice during acute bleeding. In the absence
      of active bleeding, the lesion resembles a raised nipple or visible vessel. There
      are no guidelines regarding effective selective therapy for DL, when diagnosed,
      endoscopist experience is the major determinant of the treatment strategy.
      Following our strategy, an expert endoscopist with a skilled assistant should
      have a high rate of successful DL diagnosis when an obscured gastrointestinal
      lesion is suspected. Cyanoacryltes compounds have been used successfully in
      management of Gastric varices and DLs. To our knowledge, there have been no
      previous reports regarding use of isoamyl-2-cyanoacrylate (AMCRYLATE((r));
      Concord Drugs Ltd., Hyderabad, India) as an effective therapy for gastric DL
      without serious complications. In our case study, Isoamyl-2-cyanoacrylate
      (AMCRYLATE((r))) was effective and safe for treating DL. Surgical wedge resection
      of the lesion should be considered as a therapeutic option if endoscopic therapy
      fails. 

PMID- 23951400
TI  - The undergraduate premedical experience in the United States: a critical review.
AB  - OBJECTIVES: To better understand the consequences of the premedical years for the
      character of (future) physicians by critically reviewing the empirical research
      done on the undergraduate premedical experience in the United States. METHODS: We
      searched ERIC, JSTOR, PubMed, Scopus, ISI Web of Science, and PsycINFO from the
      earliest available date for empirical, peer-reviewed studies of premedical
      students in the United States. We then used qualitative methods to uncover
      overall themes present in this literature. RESULTS: The initial literature search
      identified 1,168 articles, 19 of which were included for review. Reviewed
      articles were published between 1976 and 2010 with the majority published prior
      to 1990. Articles covered two broad topics: explaining attrition from the
      premedical track, and investigating the personality traits and stereotypes of
      premedical students. Self-selection bias and high attrition rates were among the
      limitations of the reviewed articles. CONCLUSIONS: There is very little current
      research on the premedical experience. Given the importance of the premedical
      years on the process of becoming a medical professional, it is imperative that we
      do more and better research on how the premedical experience shapes future
      physicians.

PMID- 23951401
TI  - Nrf2 impacts cellular bioenergetics by controlling substrate availability for
      mitochondrial respiration.
AB  - Transcription factor Nrf2 and its repressor Keap1 regulate a network of
      cytoprotective genes involving more than 1% of the genome, their best known
      targets being drug-metabolizing and antioxidant genes. Here we demonstrate a
      novel role for this pathway in directly regulating mitochondrial bioenergetics in
      murine neurons and embryonic fibroblasts. Loss of Nrf2 leads to mitochondrial
      depolarisation, decreased ATP levels and impaired respiration, whereas genetic
      activation of Nrf2 increases the mitochondrial membrane potential and ATP levels,
      the rate of respiration and the efficiency of oxidative phosphorylation. We
      further show that Nrf2-deficient cells have increased production of ATP in
      glycolysis, which is then used by the F1Fo-ATPase for maintenance of the
      mitochondrial membrane potential. While the levels and in vitro activities of the
      respiratory complexes are unaffected by Nrf2 deletion, their activities in
      isolated mitochondria and intact live cells are substantially impaired. In
      addition, the rate of regeneration of NADH after inhibition of respiration is
      much slower in Nrf2-knockout cells than in their wild-type counterparts. Taken
      together, these results show that Nrf2 directly regulates cellular energy
      metabolism through modulating the availability of substrates for mitochondrial
      respiration. Our findings highlight the importance of efficient energy metabolism
      in Nrf2-mediated cytoprotection. 

PMID- 23951402
TI  - An integrative computational analysis provides evidence for FBN1-associated
      network deregulation in trisomy 21.
AB  - Although approximately 50% of Down Syndrome (DS) patients have heart
      abnormalities, they exhibit an overprotection against cardiac abnormalities
      related with the connective tissue, for example a lower risk of coronary artery
      disease. A recent study reported a case of a person affected by DS who carried
      mutations in FBN1, the gene causative for a connective tissue disorder called
      Marfan Syndrome (MFS). The fact that the person did not have any cardiac
      alterations suggested compensation effects due to DS. This observation is
      supported by a previous DS meta-analysis at the molecular level where we have
      found an overall upregulation of FBN1 (which is usually downregulated in MFS).
      Additionally, that result was cross-validated with independent expression data
      from DS heart tissue. The aim of this work is to elucidate the role of FBN1 in DS
      and to establish a molecular link to MFS and MFS-related syndromes using a
      computational approach. To reach that, we conducted different analytical
      approaches over two DS studies (our previous meta-analysis and independent
      expression data from DS heart tissue) and revealed expression alterations in the
      FBN1 interaction network, in FBN1 co-expressed genes and FBN1-related pathways.
      After merging the significant results from different datasets with a Bayesian
      approach, we prioritized 85 genes that were able to distinguish control from DS
      cases. We further found evidence for several of these genes (47%), such as FBN1,
      DCN, and COL1A2, being dysregulated in MFS and MFS-related diseases.
      Consequently, we further encourage the scientific community to take into account
      FBN1 and its related network for the study of DS cardiovascular characteristics. 

PMID- 23951403
TI  - The septum transversum mesenchyme induces gall bladder development.
AB  - The liver, gall bladder, and ventral pancreas are formed from the posterior
      region of the ventral foregut. After hepatic induction, Sox17+/Pdx1+
      pancreatobiliary common progenitor cells differentiate into Sox17+/Pdx1- gall
      bladder progenitors and Sox17-/Pdx1+ ventral pancreatic progenitors, but the cell
      extrinsic signals that regulate this differentiation process are unknown. This
      study shows that the septum transversum mesenchyme (STM) grows in the posterior
      direction after E8.5, becoming adjacent to the presumptive gall bladder region,
      to induce gall bladder development. In this induction process, STM-derived BMP4
      induces differentiation from common progenitor cells adjacent to the STM into
      gall bladder progenitor cells, by maintaining Sox17 expression and suppressing
      Pdx1 expression. Furthermore, the STM suppresses ectopic activation of the liver
      program in the posterior region of the ventral foregut following hepatic
      induction through an Fgf10/Fgfr2b/Sox9 signaling pathway. Thus, the STM plays
      pivotal roles in gall bladder development by both inductive and suppressive
      effects. 

PMID- 23951404
TI  - Functional cooperation of spns2 and fibronectin in cardiac and lower jaw
      development.
AB  - The lipid mediator sphingosine-1-phosphate (S1P) is a regulator of cardiac
      development in zebrafish, as disruption of its receptor s1pr2 or transporter
      spns2 causes migration defects in cardiac progenitors. To examine the genetic
      interaction of S1P signaling and the cell adhesion molecule fibronectin, we have
      established a fn;spns2 double mutant. Cardiac migration defects in fn;spns2
      mutants were more severe than those in fn or spns2 mutants. We further found that
      the lower jaw morphology was disorganized in the fn;spns2 mutant, while it had a
      slightly shortened anterior-posterior distance in the ventral pharyngeal arch in
      fn and spns2 mutants relative to wild type. Knockdown of fn in the s1pr2 mutant,
      but not in the s1pr1 mutant, resulted in severe defects in cardiac migration and
      ventral pharyngeal arch arrangement. Further, in the background of the fn mutant,
      knockdown of endothelin receptor A (ednra), which was downregulated in the spns2
      mutant, caused pharyngeal defects resembling those in the fn;spns2 mutant. These
      results strongly suggest that Spns2-S1PR2 signaling and fibronectin cooperatively
      regulate both cardiac and lower jaw development in zebrafish. 

PMID- 23951405
TI  - Drosophila integrin adhesion complexes are essential for hemocyte migration in
      vivo.
AB  - Cell migration is an important biological process which has been intensively
      studied in the past decades. Numerous techniques, mainly involving two
      dimensional cell culture systems, have contributed to dissecting the essential
      mechanisms underlying this process. However, the development of three-dimensional
      cell culture and in vivo systems has shown some differences with what was
      previously believed to be well-established cell migration mechanisms, suggesting
      that two-dimensional cell motility would be a poor predictor of in vivo
      behaviour. Drosophila is a widely recognized model organism to study
      developmental and homeostatic processes and has been widely used to investigate
      cell migration. Here, we focus on the migration of small groups of pupal
      hemocytes that accumulate during larval stages in dorsal patches. We show that
      integrins, and other known nascent adhesion-related proteins such as Rhea and
      Fermitin 1, are crucial for this process and that their depletion does not affect
      polarization in response to environmental cues. We also present evidence for the
      importance of adhesion maturation-related proteins in hemocyte migration, namely
      Zyxin. Zyxin depletion in hemocytes leads to a significant increase of cell speed
      without affecting their response to a chemotactic cue. This is the first report
      of a systematic analysis using Drosophila melanogaster hemocytes to study
      adhesion-related proteins and their function in cell migration in vivo. Our data
      point to mechanisms of cell migration similar to those described in three
      dimensional in vitro systems and other in vivo model organisms. 

PMID- 23951406
TI  - Analysis of the cartilage proteome from three different mouse models of genetic
      skeletal diseases reveals common and discrete disease signatures.
AB  - Pseudoachondroplasia and multiple epiphyseal dysplasia are genetic skeletal
      diseases resulting from mutations in cartilage structural proteins. Electron
      microscopy and immunohistochemistry previously showed that the appearance of the
      cartilage extracellular matrix (ECM) in targeted mouse models of these diseases
      is disrupted; however, the precise changes in ECM organization and the
      pathological consequences remain unknown. Our aim was to determine the effects of
      matrilin-3 and COMP mutations on the composition and extractability of ECM
      components to inform how these detrimental changes might influence cartilage
      organization and degeneration. Cartilage was sequentially extracted using
      increasing denaturants and the extraction profiles of specific proteins
      determined using SDS-PAGE/Western blotting. Furthermore, the relative composition
      of protein pools was determined using mass spectrometry for a non-biased semi
      quantitative analysis. Western blotting revealed changes in the extraction of
      matrilins, COMP and collagen IX in mutant cartilage. Mass spectrometry confirmed
      quantitative changes in the extraction of structural and non-structural ECM
      proteins, including proteins with roles in cellular processes such as protein
      folding and trafficking. In particular, genotype-specific differences in the
      extraction of collagens XII and XIV and tenascins C and X were identified;
      interestingly, increased expression of several of these genes has recently been
      implicated in susceptibility and/or progression of murine osteoarthritis. We
      demonstrated that mutation of matrilin-3 and COMP caused changes in the
      extractability of other cartilage proteins and that proteomic analyses of Matn3
      V194D, Comp T585M and Comp DelD469 mouse models revealed both common and discrete
      disease signatures that provide novel insight into skeletal disease mechanisms
      and cartilage degradation. 

PMID- 23951408
TI  - The Hippo pathway acts via p53 and microRNAs to control proliferation and
      proapoptotic gene expression during tissue growth.
AB  - The Hippo pathway has a central role in coordinating tissue growth and apoptosis.
      Mutations that compromise Hippo pathway activity cause tissue overgrowth and have
      been causally linked to cancer. In Drosophila, the transcriptional coactivator
      Yorkie mediates Hippo pathway activity to control the expression of cyclin E and
      Myc to promote cell proliferation, as well as the expression of bantam miRNA and
      DIAP1 to inhibit cell death. Here we present evidence that the Hippo pathway acts
      via Yorkie and p53 to control the expression of the proapoptotic gene reaper.
      Yorkie further mediates reaper levels post-transcriptionally through regulation
      of members of the miR-2 microRNA family to prevent apoptosis. These findings
      provide evidence that the Hippo pathway acts via several distinct routes to limit
      proliferation-induced apoptosis. 

PMID- 23951407
TI  - The responses of neural stem cells to the level of GSK-3 depend on the tissue of
      origin.
AB  - Neural stem cells (NSCs) can be obtained from a variety of sources, but not all
      NSCs exhibit the same characteristics. We have examined how the level of glycogen
      synthase kinase-3 activity regulates NSCs obtained from different sources: the
      mouse embryonic striatum, embryonic hippocampus, and mouse ES cells. Growth of
      striatal NSCs is enhanced by mild inhibition of GSK-3 but not by strong
      inhibition that is accompanied by Wnt/TCF transcriptional activation. In
      contrast, the growth of hippocampal NSCs is enhanced by both mild inhibition of
      GSK-3 as well as stronger inhibition. Active Wnt/TCF signaling, which occurs
      normally in the embryonic hippocampus, is required for growth of neural stem and
      progenitor cells. In the embryonic striatal germinal zone, however, TCF signaling
      is normally absent and its activation inhibits growth of NSCs from this region.
      Using a genetic model for progressive loss of GSK-3, we find that primitive ES
      cell-derived NSCs resemble striatal NSCs. That is, partial loss of GSK-3 alleles
      leads to an increase in NSCs while complete ablation of GSK-3, and activation of
      TCF-signaling, leads to their decline. Furthermore, expression of dominant
      negative TCF-4 in the GSK-3-null background was effective in blocking expression
      of Wnt-response genes and was also able to rescue neuronal gene expression. These
      results reveal that GSK-3 regulates NSCs by divergent pathways depending on the
      tissue of origin. The responses of these neural precursor cells may be contingent
      on baseline Wnt/TCF signaling occurring in a particular tissue. 

PMID- 23951409
TI  - Intra-ER sorting of the peroxisomal membrane protein Pex3 relies on its luminal
      domain.
AB  - Pex3 is an evolutionarily conserved type III peroxisomal membrane protein
      required for peroxisome formation. It is inserted into the ER membrane and sorted
      via an ER subdomain (the peroxisomal ER, or pER) to peroxisomes. By constructing
      chimeras between Pex3 and the type III ER membrane protein Sec66, we have been
      able to separate the signals that mediate insertion of Pex3 into the ER from
      those that mediate sorting within the ER to the pER subdomain. The N-terminal 17
      amino acid segment of Pex3 contains two signals that are each sufficient for
      sorting to the pER: a chimeric protein containing the N-terminal domain of Pex3
      fused to the transmembrane and cytoplasmic segments of Sec66 sorts to the pER in
      wild type cells, and does not colocalise with peroxisomes. Subsequent transport
      to existing peroxisomes requires the Pex3 transmembrane segment. When expressed
      in Drosophila S2R+ cells, ScPex3 targeting to peroxisomes is dependent on the
      intra-ER sorting signals in the N-terminal segment. The N-terminal segments of
      both human and Drosophila Pex3 contain intra-ER sorting information and can
      replace that of ScPex3. Our analysis has uncovered the signals within Pex3
      required for the various steps of its transport to peroxisomes. Our generation of
      versions of Pex3 that are blocked at each stage along its transport pathway
      provides a tool to dissect the mechanism, as well as the molecular machinery
      required at each step of the pathway. 

PMID- 23951410
TI  - Regulation of Cullin-RING ubiquitin ligase 1 by Spliceosome-associated protein
      130 (SAP130).
AB  - Cullin-RING ubiquitin ligases (CRLs) mediate the ubiquitination of numerous
      protein substrates and target them for proteasomal degradation. The function of
      CRLs is under tight regulation by Cullin-binding proteins. It has been reported
      that the Spliceosome-associated protein 130 (SAP130/SF3b-3) binds to several
      Cullin proteins, yet it remains unknown whether SAP130 plays any role in
      regulating the function of CRLs. Here, we report that SAP130 overexpression
      reduces the binding of adaptor protein Skp1 and substrate receptor Skp2 to Cul1,
      whereas it has no effect on CAND1 binding to Cul1. Overexpression of SAP130
      decreases the degradation rate of p27, a protein substrate of the SCF(Skp2)
      ligase. Interestingly, silencing of SAP130 also inhibits the degradation of p27,
      suggesting a dual role for SAP130 in the regulation of SCF activity. We
      hypothesized that the regulatory role of SAP130 could extend to other CRLs;
      however, overexpression of SAP130 is unable to affect the protein stability of
      the Cul2 and Cul3 substrates, HIF-1 and NRF-2. SAP130 binds to Cul1, Cul2 and
      Cul4 with similar affinity, and it binds to Cul3 more strongly. SAP130 localizes
      in both the nucleus and the cytoplasm. Hence, the inability of SAP130 to regulate
      Cul2 and Cul3 CRLs cannot be explained by low binding affinity of SAP130 to these
      cullins or by subcellular sequestration of SAP130. We propose a novel role for
      SAP130 in the regulation of SCF, whereby SAP130 physically competes with the
      adaptor protein/F-box protein for Cul1 binding and interferes with the assembly
      of a functional SCF ligase. 

PMID- 23951411
TI  - Non-directional radial intercalation dominates deep cell behavior during
      zebrafish epiboly.
AB  - Epiboly is the first coordinated cell movement in most vertebrates and marks the
      onset of gastrulation. During zebrafish epiboly, enveloping layer (EVL) and deep
      cells spread over the vegetal yolk mass with a concomitant thinning of the deep
      cell layer. A prevailing model suggests that deep cell radial intercalations
      directed towards the EVL would drive deep cell epiboly. To test this model, we
      have globally recorded 3D cell trajectories for zebrafish blastomeres between
      sphere and 50% epiboly stages, and developed an image analysis framework to
      determine intercalation events, intercalation directionality, and migration speed
      for cells at specific positions within the embryo. This framework uses Voronoi
      diagrams to compute cell-to-cell contact areas, defines a feature-based spatio
      temporal model for intercalation events and fits an anatomical coordinate system
      to the recorded datasets. We further investigate whether epiboly defects in MZspg
      mutant embryos devoid of Pou5f1/Oct4 may be caused by changes in intercalation
      behavior. In wild-type and mutant embryos, intercalations orthogonal to the EVL
      occur with no directional bias towards or away from the EVL, suggesting that
      there are no directional cues that would direct intercalations towards the EVL.
      Further, we find that intercalation direction is independent of the previous
      intercalation history of individual deep cells, arguing against cues that would
      program specific intrinsic directed migration behaviors. Our data support a
      dynamic model in which deep cells during epiboly migrate into space opening
      between the EVL and the yolk syncytial layer. Genetic programs determining cell
      motility may control deep cell dynamic behavior and epiboly progress. 

PMID- 23951412
TI  - NGF signaling in PC12 cells: the cooperation of p75(NTR) with TrkA is needed for
      the activation of both mTORC2 and the PI3K signalling cascade.
AB  - PC12-27, a PC12 clone characterized by high levels of the transcription repressor
      REST and by very low mTORC2 activity, had been shown to be unresponsive to NGF,
      possibly because of its lack of the specific TrkA receptor. The neurotrophin
      receptor repressed by high REST in PC12-27 cells, however, is shown now to be not
      TrkA, which is normal, but p75(NTR), whose expression is inhibited at the
      transcriptional level. When treated with NGF, the PC12-27 cells lacking p75(NTR)
      exhibited a defective TrkA autophosphorylation restricted, however, to the
      TrkA(Y490) site, and an impairment of the PI3K signaling cascade. This defect was
      sustained in part by a mTORC1-dependent feed-back inhibition that in wtPC12 cells
      appeared marginal. Transfection of p75(NTR) to a level and surface distribution
      analogous to wtPC12 did not modify various high REST-dependent properties of PC12
      27 cells such as high beta-catenin, low TSC2 and high proliferation rate. In
      contrast, the defective PI3K signaling cascade and its associated mTORC2 activity
      were largely rescued together with the NGF-induced neurite outgrowth response.
      These changes were not due to p75(NTR) alone but required its cooperation with
      TrkA. Our results demonstrate that, in PC12, high REST induces alterations of NGF
      signaling which, however, are indirect, dependent on the repression of p75(NTR);
      and that the well-known potentiation by p75(NTR) of the TrkA signaling does not
      concern all the effects induced by NGF but primarily the PI3K cascade and its
      associated mTORC2, a complex known to play an important role in neural cell
      differentiation. 

PMID- 23951413
TI  - LRP5 and bone mass regulation: Where are we now?
AB  - The discovery of causal mutations in the low-density lipoprotein receptor-related
      protein 5 (LRP5) gene underlying conditions of altered bone mass ushered in a new
      era in bone research. Since those original publications, the role of Lrp5 and the
      Wnt/beta-catenin signaling pathway controlled by Lrp5 and its homologs, Lrp6 and
      Lrp4, in bone mass regulation has been an intense area of investigation. Studies
      to date have implicated this pathway in skeletal development, osteoblast
      differentiation and proliferation, osteoblast/osteocyte apoptosis, regulation of
      the balance between osteogenesis-chondrogenesis-adipogenesis, regulation of
      osteoclastogenesis and the response of bone to mechanical loading. Interestingly,
      the data from knockout and transgenic mice involving Lrp4/5/6 and/or their
      regulators, as well as beta-catenin signaling pathway components, and in vitro
      studies have sometimes yielded conflicting results. Adding to the complexity of
      the system are the studies that suggested Lrp5 regulated bone mass through a gut
      bone endocrine signaling system involving Lrp5 mediated control of gut serotonin
      synthesis. However, recent studies have called this into question and so this
      provocative concept remains an open question. Clearly, the manipulation of
      Lrp5/Wnt/beta-catenin pathway presents as a major target for drug development to
      treat diseases of low bone mass such as osteoporosis and these new therapies are
      in full progress. At present, although it is clear that Lrp5 has a role in bone
      mass regulation, much of the details remain to be elucidated and this is a major
      and exciting challenge for future studies. 

PMID- 23951414
TI  - Sex steroids and bone health in men.
AB  - The influence of sex steroids on bone in both men and women has long been
      recognized. In men, however, the relative contribution of androgens versus
      estrogens in the regulation of bone metabolism remains uncertain. Animal studies
      demonstrate that both estradiol (E2), via activation of estrogen receptor-alpha,
      and testosterone (T), via activation of the androgen receptor, regulate bone mass
      in male rodents. The main focus of this review is to summarize and discuss recent
      findings from the osteoporotic fractures in men (MrOS) cohorts regarding the
      impact of serum sex steroids on bone health in elderly men. Collectively, these
      data demonstrate that serum E2 is directly associated with bone mineral density
      (BMD) and that low serum E2 associates with higher rates of bone loss and
      fracture. In addition, they substantiate the concept of a threshold E2 level that
      determines fracture risk in elderly men. We propose that the effect of E2 on
      fracture risk is at least partly mediated by its effect on BMD, whereas the more
      modest effect of T on fracture risk mainly is mediated by effects on muscle
      strength and risk of falls. Findings from the MrOS cohorts also demonstrate that
      racial and genetic variations in aromatase activity influence serum E2 levels in
      men. In conclusion, there is compelling evidence that not only androgens, but
      also estrogens, are important regulators of bone health in men. Consequently, E2
      should not exclusively be regarded as the 'female hormone' but as a sex steroid
      that is necessary for maintenance of bone health in men. 

PMID- 23951416
TI  - TSH acts directly on osteoblasts to increase bone production.

PMID- 23951415
TI  - Notch signaling: mediator and therapeutic target of bone metastasis.
AB  - The Notch signaling pathway regulates several distinct cellular programs that are
      indispensible for proper embryonic development and maintenance of adult tissue
      homeostasis. Among the various organs of the human body, the pathway has an
      important role in the bone microenvironment, managing cell-fate decisions in two
      bone-specific cells. Significantly, pathological activation of the Notch pathway
      in these cells by metastatic tumor cells promotes osteolytic colonization of the
      bone. Armed with this knowledge, disruption of the Notch pathway, and other bone
      microenvironment signaling components that facilitate Notch-mediated bone
      metastasis, may serve as a viable therapeutic intervention in this aggressive,
      incurable disease. 

PMID- 23951417
TI  - Delayed-release bisphosphonate taken with food could improve compliance.

PMID- 23951418
TI  - Osteocytes and chondrocytes embedded in bone matrix control bone remodelling.

PMID- 23951420
TI  - Osteoblasts: skeletal controllers of energy metabolism.

PMID- 23951419
TI  - PTH accelerates pelvic fracture healing in elderly, osteoporotic women.

PMID- 23951422
TI  - Osteoporosis treatment should focus on bone mineral density.

PMID- 23951423
TI  - Osteoclasts not always needed for HSC production.

PMID- 23951424
TI  - NCoR1 builds bigger muscles in mice.

PMID- 23951421
TI  - Insights into bone health in Duchenne muscular dystrophy.
AB  - Poor bone health is a significant problem for patients with Duchenne muscular
      dystrophy (DMD), a progressive, disabling disease. Although the primary focus of
      DMD disease pathogenesis is degeneration of striated muscle, impairment of bone
      health likely has a role in the disease that has only been superficially examined
      to date. Deficiency of bone mineral density and increased incidence of bone
      fractures are well-recognized clinical components of the DMD phenotype.
      Furthermore, therapy with corticosteroids, an approved treatment for DMD that
      prolongs ambulation, may have multiple effects on bone health in DMD patients.
      This review examines the evidence in preclinical models and in human DMD disease
      that provides insight into the role performed by bone in the disease pathogenesis
      and phenotype of DMD. The information reviewed here points toward the need for
      mechanistic and therapeutic studies to optimize bone health in DMD patients. 

PMID- 23951426
TI  - Biglycan: an important regulator of Wnt signalling in the bone matrix.

PMID- 23951425
TI  - Alendronate decreases upper GI cancer death risk.

PMID- 23951427
TI  - Denosumab 5-year data in postmenopausal women with osteoporosis.

PMID- 23951428
TI  - Sclerostin regulates RANKL expression in osteocytes.

PMID- 23951429
TI  - Mechanism that underlies expansion of distant bone metastases.

PMID- 23951430
TI  - Periostin induced by tumor cells supports distant metastases.

PMID- 23951431
TI  - The rate of osteonecrosis of the jaw in patients with bone metastases.

PMID- 23951432
TI  - Denosumab delays bone metastasis in prostate cancer.

PMID- 23951433
TI  - Genetic basis of Myhre syndrome.

PMID- 23951434
TI  - Potential therapy for Rubinstein-Taybi syndrome.

PMID- 23951435
TI  - The molecular basis of cherubism.

PMID- 23951436
TI  - Bone morphogenetic protein 7 suppresses distant tumor metastasis.

PMID- 23951437
TI  - A microRNA regulon inhibits metastasis of breast cancer to bone.

PMID- 23951438
TI  - New susceptibility loci for ankylosing spondylitis (AS) identified.

PMID- 23951439
TI  - MTHFR C667T polymorphism marginally associated with fracture risk.

PMID- 23951440
TI  - Evidence mounts that MPP7 is a susceptibility gene for osteoporosis.

PMID- 23951441
TI  - FAM3c gene variant rs7776725 is important in osteoporosis risk.

PMID- 23951443
TI  - Poor vascularization may not be a factor in nonunion fractures.

PMID- 23951442
TI  - Bone metabolism and fracture risk in type 2 diabetes mellitus.
AB  - Osteoporosis and type 2 diabetes mellitus (T2DM), both prevalent in aging and
      westernized societies, adversely affect the health of elderly people by causing
      fractures and vascular complications, respectively. Recent experimental and
      clinical studies show that the disorders are etiologically related through the
      actions of osteocalcin and adiponectin. Meta-analyses of multiple clinical
      studies show that the hip fracture risk of T2DM patients is increased 1.4-1.7
      fold compared with non-DM controls, even though the patients' bone mineral
      density (BMD) is not diminished. Vertebral fracture risk of the T2DM patients is
      also increased, and BMD measurement is not sensitive enough to assess this risk.
      These findings suggest that bone fragility in T2DM patients depends on bone
      quality deterioration rather than bone mass reduction. Surrogate markers are
      therefore needed to supplement the partial effectiveness of BMD testing in
      assessing the fracture risk of the T2DM patients. Markers related to advanced
      glycation end products may be candidates. These substances modulate bone quality
      in DM. Until research establishes the usefulness of surrogate markers, physicians
      should assess fracture risk in T2DM patients not only by measuring the BMD, but
      also by taking a fracture history and evaluating prior vertebral fractures using
      spinal X-rays. 

PMID- 23951444
TI  - Clarifying the role of myostatin after bone and muscle injury.

PMID- 23951445
TI  - Galpha proteins, the Wnt/beta-catenin pathway and fibrous dysplasia.

PMID- 23951446
TI  - Does high dose vitamin D therapy reduce exacerbations in COPD?

PMID- 23951447
TI  - DNA methylation and its role in bone formation and resorption.

PMID- 23951448
TI  - Osteoclasts and hematopoiesis.
AB  - The skeletal tissue is closely associated with the hematopoietic tissue lodged in
      its inner cavities. Besides the well-known role of the endosteal osteoblasts in
      the maintenance of the hematopoietic stem cell (HSC) niche, it is an emerging
      concept that osteoclasts are involved in the regulation of hematopoiesis as well,
      although published data are still incomplete and somehow controversial. We
      reviewed the literature, and report here our perspective on the close
      relationship between bone resorption and HSC permanence in bone or egress to the
      circulation. We discussed the pressure that bone diseases exert on the
      development of hematological alterations, as well as the role of calcium and
      osteoclast enzymes in the regulation of HSC homeostasis. Genetic studies and
      preclinical experiments are described, which unveiled how bone disorders and
      treatments aimed at restoring the bone mass affect hematopoiesis, with consequent
      clinical implications. We conclude that this new field of investigation must be
      extended to unequivocally establish the role of osteoclasts in myelopoiesis and
      lymphopoiesis, and to envision treatments that can help hematological failures to
      be cured along with the associated bone alterations. 

PMID- 23951450
TI  - Spinal muscle density is a risk factor for hyperkyphosis.

PMID- 23951451
TI  - Simvastatin gel elicits fracture healing.

PMID- 23951449
TI  - Histomorphometric interpretation of bone biopsies for the evaluation of
      osteoporosis treatment.
AB  - Bone histomorphometry is a valuable tool in the evaluation of bone safety and the
      mechanism of action of drugs used in the treatment of osteoporosis. Recent
      studies in patients treated with anti-resorptive agents have highlighted
      technical issues, in particular, related to the calculation of dynamic indices of
      bone turnover using fluorochrome labelling. This review addresses the need for
      standardised approaches for overcoming these problems in order to enable valid
      comparison of the effects of different interventions on bone remodelling. 

PMID- 23951452
TI  - Ibandronate: longer dosing intervals aid fracture healing.

PMID- 23951453
TI  - Ape vertebrae reveal why elderly humans risk spinal fractures.

PMID- 23951454
TI  - Osteoprogenitor cells show therapeutic potential for bone repair.

PMID- 23951455
TI  - Increasing lean body mass boosts bone mineral density.

PMID- 23951456
TI  - Osteocytes and calcium homeostasis.

PMID- 23951458
TI  - Deleting Mef2c in mice increases bone mass.

PMID- 23951457
TI  - The skeletal muscle secretome: an emerging player in muscle-bone crosstalk.
AB  - In vitro and in vivo studies provide evidence that a variety of growth factors
      and cytokines are actively secreted by muscle tissue. Muscle can therefore
      function as an endocrine and paracrine organ. These peptides characterize the
      muscle secretome, and many muscle-derived factors such as insulin-like growth
      factor-1, basic fibroblast growth factor, interleukin-15, myostatin and secreted
      protein acidic and rich in cysteine (osteonectin) are also known to have
      significant effects on bone metabolism. The factors secreted by muscle may vary
      according to muscle activity, in that muscle contraction, muscle atrophy or
      traumatic muscle injury can alter the type and relative abundance of particular
      factors released from muscle cells. The molecular and cellular pathways by which
      muscle-derived factors affect different types of bone cells (for example,
      osteoblasts, osteoclasts and osteocytes) are, however, poorly understood.
      Nevertheless, these findings further underscore the complex nature of muscle-bone
      interactions, and highlight the importance of integrating muscle biology and
      physiology into our understanding of bone growth, development and aging. 

PMID- 23951459
TI  - Role of the nuclear envelope in the pathogenesis of age-related bone loss and
      osteoporosis.
AB  - The nuclear envelope is the most important border in the eukaryotic cell. The
      role of the nuclear envelope in cell differentiation and function is determined
      by a constant interaction between the elements of the nuclear envelope and the
      transcriptional regulators involved in signal transcription pathways. Among those
      components of the nuclear envelope, there is a growing evidence that changes in
      the expression of A-type lamins, which are essential components of the nuclear
      lamina, are associated with age-related changes in bone affecting the capacity of
      differentiation of mesenchymal stem cells into osteoblasts, favoring adipogenesis
      and affecting the function and survival of the osteocytes. Overall, as A-type
      lamins are considered as the 'guardians of the soma', these proteins are also
      essential for the integrity and quality of the bone and pivotal for the longevity
      of the musculoskeletal system. 

PMID- 23951461
TI  - Reduced bone remodeling in Type 1 Diabetes may increase fracture risk.

PMID- 23951460
TI  - Therapeutic inhibition of cathepsin K-reducing bone resorption while maintaining
      bone formation.
AB  - Osteoporosis is a disease of high bone remodeling with an imbalance of bone
      resorption over bone formation, resulting in decreased bone mineral density and
      deterioration of bone microarchitecture. From the emerging understandings of the
      molecular and cellular regulators of bone remodeling, potential new targets for
      therapeutic intervention for this disease have been identified. Cathepsin K
      (CatK), a cysteine protease produced by osteoclasts, is the primary enzyme
      mediating the degradation of the demineralized bone matrix. Current genetic and
      pharmacological evidence from studies in multiple preclinical species have
      consistently demonstrated that inhibition of CatK results in the reduction of
      bone resorption while allowing bone formation to continue. Early results from
      clinical studies with several investigational CatK inhibitors indicate that the
      impact of CatK inhibition on bone formation is distinct from that of either the
      bisphosphonates or the anti-receptor activator of nuclear factor-kappaB ligand
      antibody, denosumab. Odanacatib, a highly selective, reversible and potent
      inhibitor of CatK, is currently in phase III clinical trials for the treatment of
      postmenopausal osteoporosis. 

PMID- 23951462
TI  - FRAX from WHO underestimates fracture risk in diabetes.

PMID- 23951463
TI  - Are atypical femur fractures linked with oral bisphosphonate use?

PMID- 23951464
TI  - BMD testing in older postmenopausal women: how often?

PMID- 23951465
TI  - Therapeutic potential of adding an MSC-specific ligand to alendronate.

PMID- 23951466
TI  - Osteoporosis screening in postmenopausal women: how and when?

PMID- 23951467
TI  - GDF15 and AXII could be therapeutic targets in multiple myeloma.

PMID- 23951468
TI  - Targeting L1CAM and DDR1 may reduce bone metastasis in NSCLC.

PMID- 23951469
TI  - miR-20a facilitates metastasis of osteosarcoma cells to lung tissue.

PMID- 23951470
TI  - Cathepsin B: could it prevent bone metastases from breast cancer?

PMID- 23951471
TI  - Delivery system enables siRNA against Plekho1 to boost bone formation.

PMID- 23951472
TI  - CT-based handling and analysis of preclinical multimodality imaging data of bone
      metastases.
AB  - The pathogenesis of bone metastases is a complex and multifaceted process. Often
      multiple imaging modalities are needed to follow both the structural and
      functional changes over time during metastatic bone disease. Researchers face
      extended data sets of one experiment acquired with multiple modalities at
      multiple points in time. This review gives an overview of an integrated approach
      for handling these kinds of complex data. It focuses on the analysis of whole
      body micro-computerized tomography and optical data handling. We show how
      researchers can generate side-by-side visualizations of scans taken with one
      imaging modality at multiple time points and with multiple modalities at one
      point. Moreover, we highlight methods for normalized volumes of interest
      selection and quantification of bone volume and thickness. 

PMID- 23951474
TI  - Longer-term osteoporosis treatment may be advantageous.

PMID- 23951475
TI  - A2BAR and cAMP signaling direct osteoblast differentiation.

PMID- 23951473
TI  - Cross-talk between T cells and osteoclasts in bone resorption.
AB  - Osteoclasts (OCs) are the exclusive bone resorptive cell, they derive from
      monocyte/macrophage precursors, which can circulate within the hematopoietic cell
      pool or be resident in a number of tissues. The maintenance of an adequate bone
      mass depends on the controlled and timely removal of old, damaged bone. The
      increase of OC activity is observed in many pathologies characterised by bone
      loss, such as osteoporosis, rheumatoid arthritis, bone metastasis, periprosthetic
      osteolysis in aseptic loosening of arthroplasty and also in pediatric diseases,
      such as phenilketonuria and 21-hydroxylase deficiency. During the bone resorption
      process there is an intense cross-talk between immune system cells and OCs. In
      particular, T cells release factors and cytokines, which rule osteoclastogenesis,
      and on the other hand, OCs produce factors that act on T cells. A primary
      mediator of osteoclastogenesis is the receptor activator of nuclear factor
      kappabeta-RANK ligand-osteoprotegerin system, but also other cytokines promote OC
      activation according to the different pathologies. This review summarizes the
      main mechanisms promoting osteoclastogenesis in diseases characterised by bone
      loss, focusing on factors and cytokines involved in this process and on the
      interaction between OCs and T cells. 

PMID- 23951476
TI  - Fracture healing in mice neither enhanced nor reduced by exercise.

PMID- 23951477
TI  - Measuring movement within radial fractures treated with Volar plating.

PMID- 23951478
TI  - Characterizing osteoblasts and MSCs using in vivo techniques.

PMID- 23951479
TI  - MSCs in peripheral blood and bone marrow increase after femur injury.

PMID- 23951480
TI  - Mice that lack peripheral serotonin show reduced osteoclastogenesis.

PMID- 23951481
TI  - Wnt5a-Ror2 signaling boosts osteoclastogenesis.

PMID- 23951482
TI  - Teriparatide and fracture risk in postmenopausal women.

PMID- 23951483
TI  - An implantable wirelessly controlled teriparatide delivery device.

PMID- 23951486
TI  - Mechanical loading boosts expression of VEGF and HGF in osteocytes.

PMID- 23951485
TI  - The need for mouse models in osteoporosis genetics research.
AB  - Osteoporosis, the progressive loss of bone mass resulting in fragility fractures,
      affects ~75 million people in the United States, Europe and Japan. Bone mineral
      density (BMD) correlates with fracture risk and is widely used in clinical
      settings to predict fracture. Numerous studies have demonstrated that peak bone
      mass is highly heritable and consequently a number of genome-wide association
      studies (GWASs) have been conducted to identify the genes that regulate BMD.
      Traditional intercross mapping in the mouse has met with limited successes in the
      field of skeletal biology. With the advent of human GWAS, questions have arisen
      about the continued need for mouse models in genetics research. However,
      significant advances have been made in the field of mouse genetics, including new
      genetics resource populations and loci mapping techniques, which enable gene
      level mapping resolution. In this review, we discuss the need for mouse models to
      help understand the skeletal biology underlying novel human GWAS findings, how
      loci discovered in the mouse can be used to complement GWAS analysis and
      highlight the recent advances made in the field of skeletal biology from the use
      of these new and developing resources. We conclude this paper with a discussion
      of the need for systems-level approaches in the skeletal biology field, with an
      emphasis on the need for pathway and network analyses. 

PMID- 23951487
TI  - TNF-alpha accelerates bone fracture healing.

PMID- 23951484
TI  - The role of TGF-beta in bone metastasis: novel therapeutic perspectives.
AB  - The skeleton is a preferred site for cancer metastasis. These bone metastases
      cause dysregulated bone remodeling and the associated morbidity of fractures,
      pain, hypercalcemia and catastrophic nerve compression syndromes. Transforming
      growth factor-beta (TGF-beta) is stored in mineralized bone matrix, and released
      and activated by osteoclastic bone resorption. Once activated, TGF-beta
      stimulates nearby metastatic tumor cells within the bone microenvironment to
      secrete factors that further drive osteolytic destruction of the bone. Therefore,
      TGF-beta and its signaling constitute a critical component driving the feed
      forward vicious cycle of cancer growth in bone. Moreover, additional pro
      tumorigenic activities attributed to TGF-beta include activation of epithelial-to
      mesenchymal transition, increased tumor cell invasion, enhanced angiogenesis and
      various immunomodulatory properties. Blocking the TGF-beta signaling pathway to
      interrupt this vicious cycle and manipulate the bone microenvironment offers a
      promising area for therapeutic intervention to decrease skeletal metastasis and
      normalize bone homeostatic mechanisms. In this review, preclinical and clinical
      data are evaluated for the potential use of TGF-beta pathway inhibitors in
      clinical practice to treat bone metastases and its associated comorbidities. 

PMID- 23951489
TI  - Bone marrow stromal cells influence myeloma progression via Dkk1.

PMID- 23951490
TI  - Alendronate may be chemopreventive against colon cancer.

PMID- 23951491
TI  - Metastasis to bone or lung? Peroxiredoxin-2 expression may be the key.

PMID- 23951488
TI  - Wnt and Wnt inhibitors in bone metastasis.
AB  - Bone metastasis is a clinically devastating development of progressive cancers
      including prostate carcinoma, breast carcinoma and multiple myeloma. Bone
      metastases are typically painful, lead to adverse skeletal-related events, such
      as fracture, and are highly resistant to therapy. A major contribution to the
      ability of cancers to successfully establish bone metastases is their ability to
      exploit mechanisms of normal bone remodeling. Wnts are a large family of
      morphogenic proteins that are critical for bone development and contribute to
      maintaining bone mass in the mature organism. Wnt function is balanced by the
      presence of a variety of endogenous inhibitors, such as the dickkopf family
      members, secreted frizzled related proteins and sclerostin. Together, these
      factors contribute to normal bone homeostasis, allowing for dynamic changes in
      bone to withstand alterations in physical forces and physiological needs. In this
      review, we describe the role that Wnts and their inhibitors have in normal bone
      biology and cancer-related bone pathology. An overview of Wnt signaling pathways
      is discussed and key bone microenvironment cellular players, as they pertain to
      Wnt biology, are examined. Finally, we describe clinical trials of several Wnt
      inhibitor antagonists for patients with tumor-related bone disease. As few
      options currently exist for the treatment of bone-metastatic disease, Wnt
      proteins and their inhibitors offer promise for the development of novel
      therapeutics. 

PMID- 23951493
TI  - Sox9 shown to be a key factor in skeletogenesis.

PMID- 23951492
TI  - Mice that lack sclerostin also lack B cells.

PMID- 23951494
TI  - What's new in FGF23 research?
AB  - FGF23 is a hormone that regulates phosphate and vitamin D metabolism by binding
      to Klotho-fibroblast growth factor (FGF) receptor complex. Excess actions of
      FGF23 cause several kinds of hypophosphatemic diseases. The mechanism of
      overproduction of FGF23 in some of these diseases is becoming clear, whereas it
      is not yet completely understood. Several specific methods to inhibit FGF23
      actions have been reported as candidates for new therapies for these FGF23
      related hypophosphatemic diseases. On the other hand, many epidemiological
      studies indicated the association between high FGF23 levels and several adverse
      events in cardiovascular system, kidney, bone and mortality. FGF23 was recently
      shown to induce ventricular hypertrophy in a Klotho-independent manner. However,
      it is not yet shown whether this Klotho-independent action of FGF23 can explain
      all the results of epidemiological studies. 

PMID- 23951495
TI  - Osteoblasts control erythropoiesis via the HIF signaling pathway.

PMID- 23951497
TI  - Experimental evidence that muscle atrophy impairs fracture healing.

PMID- 23951498
TI  - A SNP in SRC-1 reduces bone density in tamoxifen-treated women.

PMID- 23951496
TI  - Osteoporosis genetics: year 2011 in review.
AB  - Increased rates of osteoporotic fractures represent a worldwide phenomenon, which
      result from a progressing aging in the population around the world and creating
      socioeconomic problems. This review will focus mostly on human genetic studies
      identifying genomic regions, genes and mutations associated with osteoporosis
      (bone mineral density (BMD) and bone loss) and related fractures, which were
      published during 2011. Although multiple genome-wide association studies (GWAS)
      were performed to date, the genetic cause of osteoporosis and fractures has not
      yet been found, and only a small fraction of high heritability of bone mass was
      successfully explained. GWAS is a successful tool to initially define and
      prioritize specific chromosomal regions showing associations with the desired
      traits or diseases. Following the initial discovery and replication, targeted
      sequencing is needed in order to detect those rare variants which GWAS does not
      reveal by design. Recent GWAS findings for BMD included WNT16 and MEF2C. The role
      of bone morphogenetic proteins in fracture healing has been explored by several
      groups, and new single-nucleotide polymorphisms present in genes such as NOGGIN
      and SMAD6 were found to be associated with a greater risk of fracture non-union.
      Finding new candidate genes, and mutations associated with BMD and fractures,
      also provided new biological connections. Thus, candidates for molecular link
      between bone metabolism and lactation (for example, RAP1A gene), as well as
      possible pleiotropic effects for bone and muscle (ACTN3 gene) were suggested. The
      focus of contemporary studies seems to move toward whole-genome sequencing,
      epigenetic and functional genomics strategies to find causal variants for
      osteoporosis. 

PMID- 23951499
TI  - RBMS3: a novel gene implicated in the risk of BRONJ.

PMID- 23951500
TI  - Novel gene implicated as a regulator of bone mineral density.

PMID- 23951501
TI  - Serotonin: good or bad for bone.
AB  - Besides its action as a neurotransmitter, serotonin has multiple physiological
      functions in several peripheral organs. Recently, Yadav et al. suggested that
      peripheral serotonin produced in the gut was a major negative regulator of
      osteoblast proliferation. These data were challenged by Cui et al. that showed no
      change in bone density in mature mice with a global invalidation of tryptophan
      hydroxylase 1, the enzyme responsible of serotonin synthesis in the periphery. In
      this context, we showed that osteoclasts are able to synthetize serotonin that
      acts locally to induce osteoclast precursors differentiation. Our data and
      previous results from others suggest that rather than acting as a hormone,
      serotonin produced in the bone could act locally on osteoclast and osteoblast
      realizing in the bone a complete micro-serotoninergic system. 

PMID- 23951502
TI  - Enzyme-replacement therapy for hypophosphatasia.

PMID- 23951503
TI  - The 5-year impact of a single dose of zoledronate.

PMID- 23951504
TI  - Osteoporosis drugs most effective in women at high fracture risk.

PMID- 23951505
TI  - PTH therapy for hypoparathyroidism impacts bone structure.

PMID- 23951506
TI  - T cells and their role in bone anabolic activity.

PMID- 23951507
TI  - Gut microbiota influences bone mass.

PMID- 23951508
TI  - NSAIDs do not appear to delay fracture healing.

PMID- 23951509
TI  - Proton pump inhibitors may slow fracture healing.

PMID- 23951510
TI  - Bisphosphonates: bone mineral affinity affects skeletal distribution.

PMID- 23951512
TI  - MicroRNAs identified that regulate osteoblast differentiation.

PMID- 23951511
TI  - Uncovering the molecular and genetic basis of osteopetrosis.

PMID- 23951513
TI  - Vitamin D [1,25(OH)2D], calcium absorption and bone quality in mice.

PMID- 23951514
TI  - Breast cancer likely to metastasise to bone if RANK expression high.

PMID- 23951516
TI  - Osteoarthritis, a disease bridging development and regeneration.
AB  - The osteoarthritic diseases are common disorders characterized by progressive
      destruction of the articular cartilage in the joints, and associated with
      remodeling of the subchondral bone, synovitis and the formation of bone
      outgrowths at the joint margins, osteophytes. From the clinical perspective,
      osteoarthritis leads to joint pain and loss of function. Osteoarthritis is the
      leading cause of progressive disability. New data from genetic, translational and
      basic research have demonstrated that pathways with essential roles in joint and
      bone development also contribute to the postnatal homeostasis of the articular
      cartilage and are involved in osteoarthritis, making these potential therapeutic
      targets. Other systems of interest are the tissue-destructive enzymes that break
      down the extracellular matrix of the cartilage as well as mediators of
      inflammation that contribute to synovitis. However, the perspective of a durable
      treatment over years to decades highlights the need for a personalized medicine
      approach encompassing a global view on the disease and its management, thereby
      including nonpharmaceutical approaches such as physiotherapy and advanced
      surgical methods. Integration of novel strategies based on their efficacy and
      safety with the identification of individuals at risk and optimal individual
      rehabilitation management remains a major challenge for the medical community in
      particular, as the incidence of osteoarthritis is likely to further increase with
      the overall aging of the population. 

PMID- 23951515
TI  - Mechanisms of multiple myeloma bone disease.
AB  - Multiple myeloma is the second most common hematological malignancy and the most
      frequent cancer to involve the skeleton. Multiple myeloma bone disease (MMBD) is
      characterized by abnormal bone remodeling with dysfunction of both bone
      resorption and bone formation, and thus can be used as a paradigm for other
      inflammatory bone diseases, and the regulation of osteoclasts and osteoblasts in
      malignancy. Studies of MMBD have identified novel regulators that increase
      osteoclastogenesis and osteoclast function, repress osteoblast differentiation,
      increase angiogenesis, or permanently alter stromal cells. This review will
      discuss the current understanding of mechanisms of osteoclast and osteoblast
      regulation in MMBD, and therapeutic approaches currently in use and under
      development that target mediators of bone destruction and blockade of bone
      formation for myeloma patients, including new anabolic therapies. 

PMID- 23951517
TI  - Increase in sclerostin levels is associated with fracture healing in humans.

PMID- 23951518
TI  - Cyclophosphamide promotes bone metastasis in prostate cancer.

PMID- 23951519
TI  - Cellular plasticity and metastatic potential.

PMID- 23951520
TI  - QTL mapping identifies a gene linked to bone mineral density.

PMID- 23951521
TI  - beta2 adrenergic receptor regulates the anabolic action of PTH in bone.

PMID- 23951522
TI  - Association between cardiovascular diseases and osteoporosis-reappraisal.
AB  - Positive association between cardiovascular diseases and osteoporosis is
      important because it concerns two major public health problems. Men and women
      with cardiovascular diseases (including severe abdominal aortic calcification
      (AAC) and peripheral arterial disease) tend to have lower areal and volumetric
      bone mineral density (BMD) as well as faster bone loss, although findings vary
      according to skeletal site. On one hand, severe forms of cardiovascular diseases
      (heart failure, myocardial infarction, hypertension, severe AAC) are associated
      with higher risk of osteoporotic fracture, especially hip fracture. This link was
      found in the studies based on healthcare databases and the cohort studies. On the
      other hand, low BMD, history of fragility fracture, vitamin D deficit and
      increased bone resorption are associated with higher risk of major cardiovascular
      events (myocardial infraction, stroke, cardiovascular mortality). Moreover,
      osteocalcin secreted by osteoblasts may be involved in the regulation of
      energetic and cardiovascular metabolism. The association between both pathologies
      depends partially on the shared risk factors, and also on the mechanisms that are
      involved in the regulation of bone and cardiovascular metabolism. Interpretation
      of the data should take into account methodological limitations:
      representativeness of the cohorts, quality of the registers and the information
      obtained from questionnaires, severity of diseases, number of events (statistical
      power) and their temporal closeness, availability of the information on potential
      confounders. It seems that patients with severe form of osteoporosis would
      benefit from assessment of the cardiovascular status and vice versa. However,
      official guidelines for the clinical practice are still lacking. 

PMID- 23951523
TI  - CXCL10 is a key player in osteolytic bone metastasis.

PMID- 23951524
TI  - How RANKL binds to RANK, and how OPG acts as 'decoy'.

PMID- 23951526
TI  - Master protease plays an important role in skull development.

PMID- 23951525
TI  - Characterizing the impact of the Fam20c gene on bone development.

PMID- 23951527
TI  - Alendronate of no benefit in avascular bone necrosis.

PMID- 23951528
TI  - Anti-citrullin antibodies and bone loss in rheumatoid arthritis.

PMID- 23951529
TI  - Semaphorin 3A and its role in osteoprotection.

PMID- 23951531
TI  - The role of SDF-1 in fracture repair.

PMID- 23951530
TI  - Reduced mineralization may contribute to osteoporotic spinal fractures.

PMID- 23951532
TI  - Is clodronate an effective adjuvant treatment in breast cancer?

PMID- 23951533
TI  - Vitamin D insufficiency in orthopaedic trauma patients in the USA.

PMID- 23951534
TI  - Healthy ageing twin study reveals role of genetic factors on BMD.

PMID- 23951535
TI  - MicroRNA-455 important in chondrogenesis.

PMID- 23951536
TI  - Bone healing augmented by experimentally induced MSC mobilization.

PMID- 23951537
TI  - CCX721 reduces osteolysis and bone tumors in a multiple myeloma model.

PMID- 23951538
TI  - Characterizing the osteoporotic rat model using new techniques.

PMID- 23951539
TI  - Role of insulin-like growth factor 1 in bone metastasis.

PMID- 23951541
TI  - Subgroup analysis for the risk of cardiovascular disease with calcium
      supplements.
AB  - Calcium supplements have been reported to increase the risk of myocardial
      infarction (MI). We wished to determine whether the effects of calcium
      supplements on cardiovascular risk vary across different population groups. We
      modeled the effect of calcium (with or without vitamin D) on the time to incident
      cardiovascular events in pre-specified subgroups based on age, dietary calcium
      intake, body mass index, smoking history, history of hypertension, diabetes and
      prevalent cardiovascular disease, using interaction terms in Cox proportional
      hazards models in two randomized controlled trial data sets-our re-analysis of
      the Women's Health Initiative Calcium and Vitamin D study (WHI CaD), and our
      pooled patient-level meta-analysis of trials of calcium supplements with or
      without vitamin D. For women in WHI CaD not taking calcium supplements at
      randomization (n=16 718), we found no significant interactions between treatment
      allocation, the risk of MI, stroke or coronary revascularization, or any of the
      baseline variables. In the pooled patient-level data set of six trials of calcium
      with or without vitamin D (n=24 869), there were also no significant interactions
      between treatment allocation, risk of MI or stroke, and any of the baseline
      variables. We found no evidence that the increased cardiovascular risk from
      calcium supplements differs across varying patient subpopulations. These findings
      suggest that targeted prescription of calcium supplements to specific population
      subgroups, such as younger people and those with low dietary calcium intake,
      should not be endorsed. 

PMID- 23951542
TI  - Negative pressure therapy stimulates healing of critical-size calvarial defects
      in rabbits.
AB  - Negative pressure therapy (NPT) is the controlled application of subatmospheric
      pressure to wounds. It has been shown to stimulate healing across a broad
      spectrum of soft-tissue wounds, at least in part from the application of
      mechanical stress on cells and tissues in the wound environment. This study tests
      the hypothesis that application of NPT to cranial critical-size defects (CSD) in
      skeletally mature rabbits leads to osseous healing. NPT was delivered 1, 4, 6 or
      10 days over CSD-containing calcium phosphate scaffolds placed in contact with
      intact dura. At 12 weeks after defect creation, NPT groups exhibited
      significantly greater defect bridging and bone within the scaffolds (P<0.01).
      Increasing duration of NPT did not result in a greater amount of bone within the
      scaffolds, but did increase the amount of bone distributed in the upper half of
      the scaffolds. Appearance of tissue within defects immediately following the
      removal of NPT at day 6 suggests alternating regions of dural compression and
      distention indicative of cell stretching. Dura and adjacent tissue were composed
      of multiple cell layers that extended up into the scaffolds, lining struts and
      populating pore spaces. An extracellular matrix densely populated with cells and
      capillaries, as well as larger vessels, infiltrated pores of NPT-treated
      scaffolds, while scattered spindle-shaped cells and sparse stroma are present
      within pores of control scaffolds. This rabbit model data suggest that NPT
      activates within mature dura a natural healing cascade that results in osseous
      tissue formation without the addition of exogenous factors or progenitor cells. 

PMID- 23951543
TI  - Novel perspectives on the transcytotic route in osteoclasts.
AB  - We analyzed the characteristics of degraded bone matrix-delivering vesicles along
      the transcytotic route from the ruffled border to the functional secretory domain
      (FSD) in bone-penetrating osteoclasts. Cells of rat or human origin were cultured
      on bovine bone slices and analyzed via confocal microscopy. Helix pomatia lectin
      binding indicated that transcytotic vesicles expose aberrant N
      acetylgalactosamine glycoconjugates, which is associated with a poor prognosis
      for a range of metastasizing human adenocarcinomas. Transcytotic vesicles fuse
      with the autophagosomal compartments and represent raft concentrates.
      Furthermore, the results of a vertical vesicle analysis suggest that multiple
      vesicle populations arise from the ruffled border and that some of these vesicles
      undergo a maturation process along the transcytotic route. Finally, our data
      suggest that the targeting of these membrane pathways may be determined by a
      novel F-actin-containing and FSD-circumscribing molecular barrier. 

PMID- 23951544
TI  - The relationships among total body fat, bone mineral content and bone marrow
      adipose tissue in early-pubertal girls.
AB  - Investigation of the physiologic relevance of bone marrow adipose tissue (BMAT)
      during growth may promote understanding of the bone-fat axis and confluence with
      metabolic factors. The objective of this pilot investigation was two-fold: (1) to
      evaluate the relationships among total body fat, bone mineral content (BMC) and
      femoral BMAT during childhood and underlying metabolic determinants and (2) to
      determine if the relationships differ by race. Participants included white and
      non-Hispanic black girls (n=59) ages 4-10 years. Femoral BMAT volume was measured
      by magnetic resonance imaging, BMC and body fat by dual-energy X-ray
      absorptiometry. Metabolic parameters were assessed in the fasted state. Total fat
      and BMC were positively associated with BMAT; however, simultaneous inclusion of
      BMC and body fat in the statistical model attenuated the association between BMC
      and BMAT. Differences in BMAT volume were observed, non-Hispanic black girls
      exhibiting marginally greater BMAT at age eight (P=0.05) and white girls
      exhibiting greater BMAT at age ten (P<0.001). Metabolic parameters conferred
      differential impact by race, such that, a positive association for BMAT and
      leptin (P=0.02) and adiponectin (P=0.002) in white girls while BMAT and insulin
      were inversely related in non-Hispanic black girls (P=0.008). Our findings
      revealed a positive relationship between BMAT, body fat and BMC, although body
      fat, respective to leptin, contributed partly to the relationship between BMAT
      and BMC. Despite large differences in total fat between non-Hispanic black and
      white, the relationship between BMAT and BMC was similar to white girls. However,
      this relationship appeared to be impacted through different mechanisms according
      to race. 

PMID- 23951545
TI  - MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling
      cascades.
AB  - RNA virus infections are detected by the RIG-I family of receptors, which induce
      type-I interferons through the mitochondrial protein MAVS. MAVS forms large prion
      like polymers that activate the cytosolic kinases IKK and TBK1, which in turn
      activate NF-kappaB and IRF3, respectively, to induce interferons. Here we show
      that MAVS polymers recruit several TRAF proteins, including TRAF2, TRAF5, and
      TRAF6, through distinct TRAF-binding motifs. Mutations of these motifs that
      disrupted MAVS binding to TRAFs abrogated its ability to activate IRF3. IRF3
      activation was also abolished in cells lacking TRAF2, 5, and 6. These TRAF
      proteins promoted ubiquitination reactions that recruited NEMO to the MAVS
      signaling complex, leading to the activation of IKK and TBK1. These results
      delineate the mechanism of MAVS signaling and reveal that TRAF2, 5, and 6, which
      are normally associated with NF-kappaB activation, also play a crucial role in
      IRF3 activation in antiviral immune responses.
      DOI:http://dx.doi.org/10.7554/eLife.00785.001. 

PMID- 23951547
TI  - UNC-13L, UNC-13S, and Tomosyn form a protein code for fast and slow
      neurotransmitter release in Caenorhabditis elegans.
AB  - Synaptic transmission consists of fast and slow components of neurotransmitter
      release. Here we show that these components are mediated by distinct exocytic
      proteins. The Caenorhabditis elegans unc-13 gene is required for SV exocytosis,
      and encodes long and short isoforms (UNC-13L and S). Fast release was mediated by
      UNC-13L, whereas slow release required both UNC-13 proteins and was inhibited by
      Tomosyn. The spatial location of each protein correlated with its effect.
      Proteins adjacent to the dense projection mediated fast release, while those
      controlling slow release were more distal or diffuse. Two UNC-13L domains
      accelerated release. C2A, which binds RIM (a protein associated with calcium
      channels), anchored UNC-13 at active zones and shortened the latency of release.
      A calmodulin binding site accelerated release but had little effect on UNC-13's
      spatial localization. These results suggest that UNC-13L, UNC-13S, and Tomosyn
      form a molecular code that dictates the timing of neurotransmitter release.
      DOI:http://dx.doi.org/10.7554/eLife.00967.001. 

PMID- 23951546
TI  - A global change in RNA polymerase II pausing during the Drosophila midblastula
      transition.
AB  - Massive zygotic transcription begins in many organisms during the midblastula
      transition when the cell cycle of the dividing egg slows down. A few genes are
      transcribed before this stage but how this differential activation is
      accomplished is still an open question. We have performed ChIP-seq experiments on
      tightly staged Drosophila embryos and show that massive recruitment of RNA
      polymerase II (Pol II) with widespread pausing occurs de novo during the
      midblastula transition. However, ~100 genes are strongly occupied by Pol II
      before this timepoint and most of them do not show Pol II pausing, consistent
      with a requirement for rapid transcription during the fast nuclear cycles. This
      global change in Pol II pausing correlates with distinct core promoter elements
      and associates a TATA-enriched promoter with the rapid early transcription. This
      suggests that promoters are differentially used during the zygotic genome
      activation, presumably because they have distinct dynamic properties.
      DOI:http://dx.doi.org/10.7554/eLife.00861.001. 

PMID- 23951548
TI  - Changing the rules of the game.
AB  - Genomics researchers have built a Facebook game that allows members of the public
      to join the effort to understand a disease that has killed millions of ash trees
      across Europe. 

PMID- 23951549
TI  - A preliminary study of functional brain activation among marijuana users during
      performance of a virtual water maze task.
AB  - Numerous studies have reported neurocognitive impairments associated with chronic
      marijuana use. Given that the hippocampus contains a high density of cannabinoid
      receptors, hippocampal-mediated cognitive functions, including visuospatial
      memory, may have increased vulnerability to chronic marijuana use. Thus, the
      current study examined brain activation during the performance of a virtual
      analogue of the classic Morris water maze task in 10 chronic marijuana (MJ) users
      compared to 18 non-using (NU) comparison subjects. Imaging data were acquired
      using blood oxygen-level dependent (BOLD) functional MRI at 3.0 Tesla during
      retrieval (hidden platform) and motor control (visible platform) conditions.
      While task performance on learning trials was similar between groups, MJ users
      demonstrated a deficit in memory retrieval. For BOLD fMRI data, NU subjects
      exhibited greater activation in the right parahippocampal gyrus and cingulate
      gyrus compared to the MJ group for the Retrieval - Motor control contrast (NU >
      MJ). These findings suggest that hypoactivation in MJ users may be due to
      differences in the efficient utilization of neuronal resources during the
      retrieval of memory. Given the paucity of data on visuospatial memory function in
      MJ users, these findings may help elucidate the neurobiological effects of
      marijuana on brain activation during memory retrieval.

PMID- 23951550
TI  - A Molecular Dynamics Simulation Study of Two Dipeptide Based Molecular Micelles:
      Effect of Amino Acid Order.
AB  - Molecular dynamics (MD) simulations were used to compare the structures of the
      chiral molecular micelles (MM) poly-(sodium undecyl-(L,L)-leucine-valine)
      (poly(SULV)) and poly-(sodium undecyl-(L,L)-valine-leucine) (poly (SUVL)). Both
      MM contained polymerized surfactant monomers tenninated by chiral dipeptide
      headgroups. The study was undertaken to investigate why poly(SULV) is generally a
      better chiral selector compared to poly(SUVL) in electrokinetic chromatography
      separations. When comparing poly(SULV) to poly(SUVL), poly(SULV) had the more
      conformational flexible dipeptide headgroup and hydrogen bond analyses revealed
      that the poly(SULV) headgroup conformation allowed a larger number of
      intramolecular hydrogen bonds to form between monomer chains. In addition, a
      larger number of water molecules surrounded the chiral centers of the poly(SULV)
      molecular micelle. Poly(SULV) was also found to have a larger solvent accessible
      surface area (SASA) than poly(SUVL) and fluctuations in the poly(SULV) SASA
      during the MD simulation allowed dynamic monomer chain motions expected to be
      important in chiral recognition to be identified. Finally, approximately 50% of
      the Na+ counterions were found in the first three solvation shells surrounding
      both MM, with the remainder located in the bulk. Overall the MD simulations point
      to both greater headgroup flexibility and solvent and analyte access to the
      chiral centers of the dipeptide headgroup as factors contributing to the enhanced
      chiral selectivity observed with poly(SULV).

PMID- 23951551
TI  - A recessive X-linked mutation causes a threefold reduction of total body zinc
      accumulation in Drosophila melanogaster laboratory strains.
AB  - A newly identified human locus on chromosome 15 was recently associated with zinc
      accumulation. Based on a prior report of a threefold difference in zinc
      accumulation between fumble(1) heterozygous mutants and control fly strains, it
      was suggested that phosphopantothenoylcysteine decarboxylase might affect zinc
      status through its effects on vitamin B5 (pantothenate) metabolism. We report
      here that outcrossed fumble(1) heterozygous mutant flies with low zinc content
      have been recovered, suggesting that pantothenate metabolism did not alter zinc
      homeostasis in fumble(1) heterozygous flies. We show instead that the Drosophila
      condition of low body zinc accumulation is an X-chromosome-linked recessive
      trait. 

PMID- 23951552
TI  - Respiratory syncytial virus (RSV) suppression of glucocorticoid receptor
      phosphorylation does not account for repression of transactivation.
AB  - Respiratory syncytial virus (RSV)-induced bronchiolitis in infants, although
      inflammatory in nature, is not responsive to glucocorticoids. We have recently
      shown that RSV-infected lung epithelial cells have impaired glucocorticoid
      receptor (GR)-mediated transactivation. In this study, we show that the N
      terminal region of GR is required for RSV repression of GR transactivation and
      that RSV infection of lung epithelial cells reduces ligand-dependent GR
      phosphorylation at serine 211 and serine 226. However, we also show that these
      changes in GR phosphorylation do not account for the RSV repression of GR
      transactivation suggesting other regions of the GR N-terminus must also be
      involved. 

PMID- 23951553
TI  - The role of the N-terminal tail for the oligomerization, folding and stability of
      human frataxin.
AB  - The N-terminal stretch of human frataxin (hFXN) intermediate (residues 42-80) is
      not conserved throughout evolution and, under defined experimental conditions,
      behaves as a random-coil. Overexpression of hFXN56-210 in Escherichia coli yields
      a multimer, whereas the mature form of hFXN (hFXN81-210) is monomeric. Thus,
      cumulative experimental evidence points to the N-terminal moiety as an essential
      element for the assembly of a high molecular weight oligomer. The secondary
      structure propensity of peptide 56-81, the moiety putatively responsible for
      promoting protein-protein interactions, was also studied. Depending on the
      environment (TFE or SDS), this peptide adopts alpha-helical or beta-strand
      structure. In this context, we explored the conformation and stability of hFXN56
      210. The biophysical characterization by fluorescence, CD and SEC-FPLC shows that
      subunits are well folded, sharing similar stability to hFXN90-210. However,
      controlled proteolysis indicates that the N-terminal stretch is labile in the
      context of the multimer, whereas the FXN domain (residues 81-210) remains
      strongly resistant. In addition, guanidine hydrochloride at low concentration
      disrupts intermolecular interactions, shifting the ensemble toward the monomeric
      form. The conformational plasticity of the N-terminal tail might impart on hFXN
      the ability to act as a recognition signal as well as an oligomerization trigger.
      Understanding the fine-tuning of these activities and their resulting balance
      will bear direct relevance for ultimately comprehending hFXN function. 

PMID- 23951554
TI  - ATAF1 transcription factor directly regulates abscisic acid biosynthetic gene
      NCED3 in Arabidopsis thaliana.
AB  - ATAF1, an Arabidopsis thaliana NAC transcription factor, plays important roles in
      plant adaptation to environmental stress and development. To search for ATAF1
      target genes, we used protein binding microarrays and chromatin
      immunoprecipitation (ChIP). This identified T[A,C,G]CGT[A,G] and TT[A,C,G]CGT as
      ATAF1 consensus binding sequences. Co-expression analysis across publicly
      available microarray experiments identified 25 genes co-expressed with ATAF1. The
      promoter regions of ATAF1 co-expressors were significantly enriched for ATAF1
      binding sites, and TTGCGTA was identified in the promoter of the key abscisic
      acid (ABA) phytohormone biosynthetic gene NCED3. ChIP-qPCR and expression
      analysis showed that ATAF1 binding to the NCED3 promoter correlated with
      increased NCED3 expression and ABA hormone levels. These results indicate that
      ATAF1 regulates ABA biosynthesis. 

PMID- 23951555
TI  - Microenvironment-Dependent Phenotypic Changes in a SCID Mouse Model for Malignant
      Mesothelioma.
AB  - BACKGROUND AND AIMS: Malignant mesothelioma is an aggressive, therapy-resistant
      tumor. Mesothelioma cells may assume an epithelioid or a sarcomatoid phenotype,
      and presence of sarcomatoid cells predicts poor prognosis. In this study, we
      investigated differentiation of mesothelioma cells in a xenograft model, where
      mesothelioma cells of both phenotypes were induced to form tumors in severe
      combined immunodeficiency mice. METHODS: Xenografts were established and
      thoroughly characterized using a comprehensive immunohistochemical panel, array
      comparative genomic hybridization (aCGH) of chromosome 3, fluorescent in situ
      hybridization, and electron microscopy. RESULTS: Epithelioid and sarcomatoid
      cells gave rise to xenografts of similar epithelioid morphology. While
      sarcomatoid-derived xenografts had higher growth rates, the morphology and
      expression of differentiation-related markers was similar between xenografts
      derived from both phenotypes. aCGH showed a convergent genotype for both
      xenografts, resembling the original aggressive sarcomatoid cell sub-line.
      CONCLUSION: Human mesothelioma xenografts from sarcomatoid and epithelioid
      phenotypes converged to a similar differentiation state, and genetic analyses
      suggested that clonal selection in the mouse microenvironment was a major
      contributing factor. This thoroughly characterized animal model can be used for
      further studies of molecular events underlying tumor cell differentiation.

PMID- 23951556
TI  - Targeted therapy; from advanced melanoma to the adjuvant setting.

PMID- 23951557
TI  - School Age Effects of the Newborn Individualized Developmental Care and
      Assessment Program for Medically Low-Risk Preterm Infants: Preliminary Findings.
AB  - BACKGROUND: By school age, even low risk moderately preterm-born children show
      more neuro-cognitive deficits, underachievement, behavioral problems, and poor
      social adaptation than full-term peers. AIM: To evaluate the outcomes at school
      age for moderately preterm-born children (29-33 weeks gestational age),
      appropriate in growth for gestational age (AGA) and medically at low-risk,
      randomized to Newborn Individualized Developmental Care and Assessment Program
      (NIDCAP) or standard care in the Newborn Intensive Care Unit. At school-age, the
      experimental (E) group will show better neuropsychological and neuro
      electrophysiological function, as well as improved brain structure than the
      control (C) group. MATERIALS AND METHODS: The original sample consisted of 30
      moderately preterm-born infants (29 to 33 weeks), 23 (8C and 15E) of them were
      evaluated at 8 years of age, corrected-for-prematurity with neuropsychological,
      EEG spectral coherence, and diffusion tensor magnetic resonance imaging (DT MRI)
      measures. RESULTS: E-performed significantly better than C-group children on the
      Kaufman Assessment Battery for Children-Second Edition (KABC-II) and trended
      towards better scores on the Rey-Osterrieth Complex Figure Test. They also showed
      more mature frontal and parietal brain connectivities, and more mature fiber
      tracts involving the internal capsule and the cingulum. Neurobehavioral results
      in the newborn period successfully predicted neuropsychological functioning at 8
      years corrected age. CONCLUSION: Moderately preterm infants cared for with the
      NIDCAP intervention showed improved neuropsychological and neuro
      electrophysiological function as well as improved brain structure at school-age.

PMID- 23951559
TI  - Impact of obesity on perinatal outcomes among asthmatic women.
AB  - BACKGROUND: Only one study has investigated the combined effect of maternal
      asthma and obesity on perinatal outcomes; however, it did not consider small-for
      gestational age and large-for-gestational age infants. OBJECTIVES: To examine the
      impact of obesity on perinatal outcomes among asthmatic women. METHODS: A cohort
      of 1386 pregnancies from asthmatic women was reconstructed using three of
      Quebec's administrative databases and a questionnaire. Women were categorized
      using their prepregnancy body mass index. Underweight, overweight and obese women
      were compared with normal weight women. The primary outcome was the birth of a
      small-for-gestational-age infant, defined as a birth weight below the 10th
      percentile for gestational age and sex. Secondary outcomes were large-for
      gestational-age infants (birth weight >90th percentile for gestational age) and
      preterm birth (<37 weeks' gestation). Logistic regression models were used to
      obtain the ORs of having small-for-gestational-age infants, large-for-gestational
      age infants and preterm birth as a function of body mass index. RESULTS: The
      proportions of underweight, normal weight, overweight and obese women were 10.8%,
      53.3%, 19.7% and 16.2%, respectively. Obese asthmatic women were not found to be
      significantly more at risk for giving birth to small-for-gestational-age infants
      (OR 0.6 [95% CI 0.4 to 1.1]), large-for-gestational-age infants (OR 1.2 [95% CI
      0.7 to 2.2]) or having a preterm delivery (OR 0.7 [95% CI 0.4 to 1.3]) than
      normal-weight asthmatic women. CONCLUSIONS: No significant negative interaction
      between maternal asthma and obesity on adverse perinatal outcomes was observed.

PMID- 23951561
TI  - Consensus Statements and Recommended Clinical Procedures Regarding Restorative
      Materials and Techniques for Implant Dentistry.
AB  - No abstract available.

PMID- 23951558
TI  - Stemming the Degeneration: IVD Stem Cells and Stem Cell Regenerative Therapy for
      Degenerative Disc Disease.
AB  - The intervertebral disc (IVD) is immensely important for the integrity of
      vertebral column function. The highly specialized IVD functions to confer
      flexibility and tensile strength to the spine and endures various types of
      biomechanical force. Degenerative disc disease (DDD) is a prevalent
      musculoskeletal disorder and is the major cause of low back pain and includes the
      more severe degenerative lumbar scoliosis, disc herniation and spinal stenosis.
      DDD is a multifactorial disorder whereby an imbalance of anabolic and catabolic
      factors, or alterations to cellular composition, or biophysical stimuli and
      genetic background can all play a role in its genesis. However, our comprehension
      of IVD formation and theetiology of disc degeneration (DD) are far from being
      complete, hampering efforts to formulate appropriate therapies to tackle DD.
      Knowledge of the stem cells and various techniques to manipulate and direct them
      to particular fates have been promising in adopting a stem-cell based
      regenerative approach to DD. Moreover, new evidence on the residence of
      stem/progenitor cells within particular IVD niches has emerged holding promise
      for future therapeutic applications. Existing issues pertaining to current
      therapeutic approaches are also covered in this review.

PMID- 23951562
TI  - Consensus Statements and Recommended Clinical Procedures Regarding Optimizing
      Esthetic Outcomes in Implant Dentistry.
AB  - No abstract available.

PMID- 23951560
TI  - Role of blind closed pleural biopsy in the managment of pleural exudates.
AB  - INTRODUCTION: The performance of blind closed pleural biopsy (BCPB) in the study
      of pleural exudates is controversial. OBJECTIVE: To assess the diagnostic yield
      of BCPB in clinical practice and its role in the study of pleural exudates.
      METHODS: Data were retrospectively collected on all patients who underwent BCPB
      performed between January 1999 and December 2011. RESULTS: A total of 658 BCPBs
      were performed on 575 patients. Pleural tissue was obtained in 590 (89.7%) of the
      biopsies. A malignant pleural effusion was found in 35% of patients. The cytology
      and the BCPB were positive in 69.2% and 59.2% of the patients, respectively. Of
      the patients with negative cytology, 21 had a positive BCPB (diagnostic
      improvement, 15%), which would have avoided one pleuroscopy for every seven BCPBs
      that were performed. Of the 113 patients with a tuberculous effusion, granulomas
      were observed in 87 and the Lowenstein culture was positive in an additional 17
      (sensitivity 92%). The overall sensitivity was 33.9%, with a specificity and
      positive predictive value of 100%, and a negative predictive value of 71%.
      Complications were recorded in 14.4% of patients (pneumothorax 9.4%; chest pain
      5.6%; vasovagal reaction, 4.1%; biopsy of another organ 0.5%). CONCLUSIONS: BCPB
      still has a significant role in the study of a pleural exudate. If an image
      guided technique is unavailable, it seems reasonable to perform BCPB before
      resorting to a pleuroscopy. These results support BCPB as a relatively safe
      technique.

PMID- 23951563
TI  - Consensus Statements and Clinical Recommendations for Implant Loading Protocols.
AB  - No abstract available.

PMID- 23951565
TI  - Consensus Statements and Recommended Clinical Procedures Regarding Contemporary
      Surgical and Radiographic Techniques in Implant Dentistry.
AB  - No abstract available.

PMID- 23951564
TI  - Consensus Statements and Clinical Recommendations for Prevention and Management
      of Biologic and Technical Implant Complications.
AB  - No abstract available.

PMID- 23951566
TI  - Hydration effects on the barrier function of stratum corneum lipids: Raman
      analysis of ceramides 2, III and 5.
AB  - The stratum corneum is the outermost layer of the skin; its barrier function is
      highly dependent on the composition and the structure as well as the organization
      of lipids in its extracellular matrix. Ceramides, free fatty acids and
      cholesterol represent the major lipid classes present in this matrix. They play
      an important role in maintaining the normal hydration levels required for the
      normal physiological function. Despite the advancement in the understanding of
      the structure, composition and the function of the stratum corneum (SC), the
      concern of "dry skin" remains important in dermatology and care research. Most
      studies focus on the quantification of water in the skin using different
      techniques including Raman spectroscopy, while the studies that investigate the
      effect of hydration on the quality of the barrier function of the skin are
      limited. Raman spectroscopy provides structural, conformational and
      organizational information that could help elucidate the effect of hydration on
      the barrier function of the skin. In order to assess the effect of relative
      humidity on the lipid barrier function; we used Raman spectroscopy to follow-up
      the evolution of the conformation and the organization of three synthetic
      ceramides (CER) differing from each other by the nature of their polar heads
      (sphingosine, phytosphingosine and alpha hydroxyl sphingosine), CER 2, III and 5
      respectively. CER III and 5 showed a more compact and ordered organization with
      stronger polar interactions at intermediate relative humidity values, while CER 2
      showed opposite tendencies to those observed with CER III and 5. 

PMID- 23951567
TI  - Integration of nanoporous membranes into microfluidic devices: electrokinetic bio
      sample pre-concentration.
AB  - The integration of nanoporous membranes into microfluidic devices allows a wide
      range of analytical and biochemical applications such as stable concentration
      gradient generation, sample pre-concentration, and ion and biomolecule filtration
      in a controllable manner. However, further applications of nanoporous membranes
      in microfluidic devices require rapid and controllable fabrication methods of
      various nanoporous precursor materials; currently, few such methods exist. Here,
      we describe simple and robust methods that can be used for microfabricating four
      different precursor materials as leakage-tight membranes in a microfluidic
      channel network. The methods consist of a common integration process and
      individual solidification processes such as solvent evaporation, UV-curing, and
      temperature treatment. We demonstrate that the fabricated membranes can be used
      for electrokinetic, nanofluidic pre-concentration of bio-samples such as
      proteins, cells, and microspheres on either the anodic or cathodic side of the
      membranes. In addition, we not only characterize the physicochemical properties
      of the membranes such as conductance of membrane-integrated microchannels,
      relative permselectivity, and pre-concentration ability, but also compare
      fabrication availability, membrane robustness, surface charge density tunability
      and biocompatibility with buffer solutions. The methods are versatile for many
      nanoporous precursor materials and easy to control the location and dimension of
      the membranes. Hence, the methods developed and the characterized properties of
      the membranes tested in this work could be widely employed for further
      applications of nanoporous membranes in microfluidic systems. 

PMID- 23951568
TI  - An electrogenerated chemiluminescence sensor prepared with a graphene/multiwall
      carbon nanotube/gold nanocluster hybrid for the determination of phenolic
      compounds.
AB  - A dispersible graphene/multiwall carbon nanotube/gold nanocluster
      (GP/MWCNTs/AuNCs) hybrid in aqueous solution was prepared in situ, and
      characterized by transmission electron microscopy (TEM) and ultraviolet-visible
      (UV-vis) spectroscopy. Based on the fact that phenolic compounds can enhance the
      electrogenerated chemiluminescence (ECL) signal at the GP/MWCNTs/AuNCs modified
      glassy carbon electrode in the presence of peroxydisulfate, an ECL sensor was
      proposed for the determination of phenolic compounds with high sensitivity, good
      repeatability and stability. Due to its fascinating features, such as good water
      solubility and excellent stability, the GP/MWCNTs/AuNCs hybrid would offer a
      suitable catalytic platform for phenolic compounds and provide potential promise
      for the construction of ECL sensors. 

PMID- 23951569
TI  - Label-free electrochemical DNA sensing with a one-target-multitriggered
      hybridization chain reaction strategy.
AB  - A one-target-multitriggered hybridization chain reaction (MHCR) strategy was
      designed for ultrasensitive electrochemical detection of DNA by combining the
      isothermal strand-displacement polymerase reaction (ISDPR) with the DNA self
      assembly on a DNA sensor surface. The sensor was constructed by immobilizing a
      hairpin-like capture probe (CP) on a gold electrode via an Au-S bond. The ISDPR
      was triggered by the hybridization of the target DNA to open the CP and primer to
      anneal the complementary part in the bottom of the exposed stem and the extension
      of the primer in the presence of dNTPs and polymerase. Each target copy could
      produce a few opened CPs. Afterwards, the other part of the exposed stem acted as
      an initiator to trigger the hybridization chain reaction (HCR) when incubated
      with two hairpin monomers. Using [Ru(NH3)6](3+) as an electrochemically active
      indicator to interact with the MHCR product, the amperometric response
      demonstrated a perfect multiple amplification effect. The constructed sensor
      showed a high sensitivity for detection of the target DNA in a linear range from
      0.1 fM to 10 pM, a detection limit down to 0.02 fM (3sigma) and good selectivity
      for base discrimination. This method did not need any modification or labelling
      process. The proposed strategy provides a powerful tool for cascade signal
      amplification and has a wide potential application in bioanalysis. 

PMID- 23951570
TI  - A biomimetic bitter receptor-based biosensor with high efficiency immobilization
      and purification using self-assembled aptamers.
AB  - It is of substantial interest to mimic mechanisms of biological sensing systems
      for the development of novel biosensors. This paper presents a novel biomimetic
      bitter receptor-based biosensor for the detection of specific bitter substances,
      in which bitter receptors were used as sensitive elements for the first time. A
      simple and practical self-assembled aptamer-based strategy was proposed for
      functional immobilization and purification of bitter receptors. A human bitter
      receptor, T2R4, was expressed on the plasma membrane of HEK-293 cells and fused
      with a His6-tag on its C-terminal. The membrane fractions containing the
      expressed T2R4 were extracted and immobilized on the gold surface of a quartz
      crystal microbalance (QCM) pretreated with a monolayer of self-assembled aptamers
      that can specifically recognize and capture biomolecules labeled with His6-tags.
      The QCM device was used to monitor the responses of T2R4 to various bitter
      stimuli. The results indicate that this biosensor can detect denatonium with high
      sensitivity and specificity, which is the specific target of T2R4. In addition,
      this biosensor shows dose-dependent responses to a certain concentration range of
      denatonium. The sensitivity of bitter receptor-based biosensors prepared by an
      aptamer-based method is 1.21 kHz mM(-1), which is 2 times higher than that
      prepared by a SAM-based method. The major advances on bitter receptor
      immobilization and purification presented in this work could substantially be
      very useful for developing other membrane receptor-based biosensors and molecular
      sensor arrays. This bitter receptor-based biosensor has great potential to be
      used as a valuable tool for bitter detection as well as for the research of taste
      signal transduction. 

PMID- 23951571
TI  - In response.

PMID- 23951572
TI  - Abstracts of the 14th Congress of the European Society for Biomedical Research on
      Alcoholism (ESBRA). September 8-11, 2013. Warsaw, Poland.

PMID- 23951573
TI  - Remembering Dr. Yasuo Idezuki, F.A.C.S, Professor Emeritus, the University of
      Tokyo.

PMID- 23951575
TI  - Retraction. Effects of fasting blood glucose, blood pressure and anti
      hypertension treatment on cardiovascular disease incidence: a 30-year follow-up
      study of 740 incident patients with Type 2 diabetes.

PMID- 23951574
TI  - Reply: To PMID 22926500.

PMID- 23951576
TI  - Reply: To PMID 23090425.

PMID- 23951577
TI  - First hand: The case of the retained peg guide.

PMID- 23951578
TI  - [A prominent Russian scientist F.V. Ovsiannikov (1827-1906)].

PMID- 23951579
TI  - [The use of memoplant (EGb 761) in clinical practice].

PMID- 23951580
TI  - [The activation of the cholinergic innervation in the treatment of diseases of
      the peripheral and central nervous system].

PMID- 23951581
TI  - [Immunization schedule 2013].

PMID- 23951582
TI  - Response.

PMID- 23951583
TI  - Response.

PMID- 23951585
TI  - Introduction to special issue on the personality inventory for DSM-5 (PID-5).

PMID- 23951584
TI  - Entecavir for the treatment of real-life chronic hepatitis B patients: a study
      from Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: Entecavir is a nucleoside analog used in the treatment
      of chronic hepatitis B. The efficacy of ETV has not been studied in the Saudi
      population. The objective of the study was to find undetectable HBV DNA after 48
      weeks completion of ETV treatment in real-life versus clinical trial patients.
      DESIGN AND SETTING: A retrospective study in a tertiary care center in Saudi
      Arabia of patients treated from 2006 January to 2010 June. PATIENTS AND METHODS:
      Of 43 eligible patients, 24 patients were treatment-naive and 19 were treatment
      refractory. RESULTS: Mean HBV DNA viral load was 51 million IU/mL prior to
      treatment and decreased to 0.16 million IU/mL at 48 weeks. Mean HBV DNA log10
      IU/mL was 6.3 before treatment and decreased to 2.3 log10 IU/mL(P=.001) at 48
      weeks. After 48 weeks treatment, ALT significantly decreased from a mean ALT of
      88.7 U/L before treatment to 37.5U/L (P=.04). After 48 weeks, the HBV DNA was
      undetectable in 14 (58.4%) in treatment-naive patients and in 6 (31.6%) treatment
      refractory patients. At 48 weeks 17 (60.7%) of HBeAg-negative patients and 3
      (20%) HBeAg-positive patients achieved undetectable HBV DNA (P=.003). When the
      treatment was extended for a median of 24 months (range 12 months to 60 months),
      29 (67.4%) achieved undetectable HBV DNA. Among 29 patients who achieved
      undetectable HBV DNA, the treatment refractory patients reached undetectability
      within a mean of 32.4 (18.6) months and treatment-naive patients in a mean of
      18.8 (10.5) months(P=.01). Two (13.3%) of HBeAg-reactive patients converted to
      HBeAg-negative status and one patient (2.3%)lost HBsAg. CONCLUSION: After
      treatment with entecavir, HBV DNA undetectable at 48 weeks in 58.4% of naive
      patients.The response rate was better in HBeAg-negative and treatment-naive
      patients compared to HBeAg-positive and treatment-refractory patients.

PMID- 23951586
TI  - Sclerosing stromal tumour of the ovary: two case reports.
AB  - Sclerosing stromal tumours are rare benign ovarian neoplasms of the sex cord
      stromal that occur predominantly in the second and third decades of life. Herein,
      we report two cases of sclerosing stromal tumour of the ovary. The two patients
      were 16 and 45 years old and both presented with pelvic pain. Ultrasonography
      demonstrated a heterogeneous solid mass of the left and right ovary,
      respectively, with some cystic foci in the second tumour. Laboratory tests
      including tumour markers and serum hormonal assays were normal in both cases. The
      two patients underwent left and right salpingo-oophrectomy, respectively.
      Microscopically, the tumours showed a pseudolobular pattern with cellular areas
      separated by oedematous and collagenous areas. The cellular areas were richly
      vascularized, with a hemangiopericytic pattern, and were composed of an admixture
      of theca-like and spindle-shaped cells. Immunohistochemical studies showed that
      the tumour cells were positive for smooth muscle actin, inhibin and vimentin, but
      negative for cytokeratin. The final pathological diagnosis was sclerosing stromal
      tumour. Postoperative course was uneventful for both patients.

PMID- 23951587
TI  - One-stop shop for care. Hospital ERs seeing increase in patients, capital.
AB  - Hospital emergency room departments are increasingly becoming a portal for
      patients to get care quickly. And hospitals are responding by transforming their
      operations. When Dr. Rich Zane, left, arrived last year as chair of the
      University of Colorado Hospital's emergency medicine department, the Aurora
      facility's ER was operating under "a process that's predicated on 1960s medicine
      and we're practicing it in 2013," he says.

PMID- 23951588
TI  - Tempered buying Firms broker fewer first-quarter deals than expected.

PMID- 23951589
TI  - A niche business. More hospitals focusing on limited service lines.

PMID- 23951590
TI  - The gamble.

PMID- 23951591
TI  - Midazolam oral transmucosal route. An alternative to rectal diazepam for some
      children.
AB  - In children, convulsive seizures lasting-more than 5 minutes constitute a life
      threatening condition. Outside of the hospital setting, the treatment of choice
      is rectal diazepam. Midazolam, a fast-acting benzodiazepine, is now authorised
      for use in this setting, in the form of a solution for oral transmucosal route.
      The results of five trials conducted in specialised centres suggest that
      midazolam oromucosal solution is at least as effective as rectal diazepam in
      reducing the duration of seizures and preventing early seizure recurrence.
      However, the evidence provided by these studies is weak. The main adverse effects
      of midazolam oromucosal solution are the same as those of rectal diazepam; in
      particular, respiratory depression occurs in 1% to 5% of patients and can
      necessitate intubation. Some anticonvulsants, such as carbamazepine, phenytoin
      and phenobarbital, may reduce the effectiveness of midazolam and diazepam. At the
      recommended doses, midazolam overdose may occur when the oromucosal solution is
      used to treat infants less than 6 months old. Midazolam oromucosal solution is
      sold in single-dose ready-to-use oral syringes. In France, diazepam doses for
      rectal administration must be prepared from a vial of solution. In early 2013,
      the usability of oral transmucosal versus rectal administration has not been
      compared prospectively in children with convulsive seizures. In practice, rectal
      diazepam is the drug of choice for paediatric convulsive seizures occurring
      outside the hospital setting. Midazolam oromucosal solution is an alternative for
      children over 6 months of age, especially when preparation or administration of
      the rectal diazepam dose poses a problem.

PMID- 23951592
TI  - Emtricitabine + tenofovir to prevent HIV transmission. More evaluation needed.
AB  - Regular condom use is the standard method for preventing HIV transmission during
      insertive intercourse. Effective treatment of infected individuals also reduces
      the risk of transmission. However, even when these preventive measures are used
      correctly, they are not completely reliable. Emtricitabine (a nucleoside) and
      tenofovir (a nucleotide) are HIV reverse transcriptase inhibitors. The
      combination of these 2 drugs has been authorised in the United States for the
      prevention of HIV-1 infection in adults at high risk, in combination with other
      preventive measures. Clinical evaluation is based mainly on two double-blind
      placebo-controlled trials. In a trial involving 2499 men or transgender women
      (born male) who have sex with men, conducted outside Europe, the incidence of
      infection was lower among patients treated with emtricitabine + tenofovir than
      with placebo (2.3 versus 4.3 per 100 person-years, p = 0.005). A subgroup
      analysis showed no added preventive effect of this treatment among condom users.
      Another trial including 4758 heterosexual couples in which only one partner was
      infected, conducted in Uganda and Kenya, showed a lower incidence of HIV
      infection in the emtricitabine + tenofovir group than in the placebo group after
      one year of treatment (0.50 versus 1.99 per 100 person-years). No statistically
      significant difference was found between the emtricitabine + tenofovir
      combination and tenofovir single-agent prophylaxis. Drug prevention showed no
      added efficacy in this trial among patients who regularly used condoms. Other
      trials conducted in Africa among heterosexuals favour the preventive efficacy of
      emtricitabine + tenofovir, except in one trial in which adherence appeared to be
      very poor. These trials did not identify any previously unknown adverse effects
      of emtricitabine + tenofovir. Tenofovir can cause kidney failure. Data from a US
      registry of pregnancies exposed to emtricitabine or tenofovir rule out any major
      risk of teratogenicity. In situations in which there is a high risk of HIV
      transmission, daily intake of emtricitabine + tenofovir appears to roughly halve
      the risk of sexual transmission, without eliminating it completely. In Western
      Europe, only persons with infected partners and those who engage in risky sexual
      practices without condoms are at high risk of infection. Long-term assessment of
      emtricitabine + tenofovir is justified in these situations, despite the mixed
      results of previous trials.

PMID- 23951593
TI  - Tranexamic acid and thrombosis.
AB  - Tranexamic acid is an antifibrinolytic drug. It therefore reduces bleeding but,
      in certain situations, it may expose patients to a risk of thrombosis. It is used
      for the treatment of various types of bleeding, including menorrhagia,
      haematuria, certain surgical procedures and trauma. Its harm-benefit balance is
      favourable in certain situations associated with serious bleeding.The harm
      benefit balance is different in minor bleeding: the expected benefits are smaller
      because the condition is not serious, and the risk of thromboembolism may be
      higher without the haemodilution associated with severe bleeding. Various drug
      regulatory agencies have received reports of thrombotic events attributed to
      tranexamic acid. In a case-control study using data from the British General
      Practice Research Database, women taking tranexamic acid had a 3-fold higher risk
      of developing deep vein thrombosis. There was a wide 95% confidence interval,
      ranging from 0.7 to 15.8; thus, a major increase in the risk of thrombosis cannot
      be ruled out. Only one comparative randomised trial assessed thrombotic events in
      53 women receiving tranexamic acid for menorrhagia; too few patients were studied
      to determine the risk. Clinical trials conducted in serious haemorrhage or in
      patients undergoing surgery with a high risk of bleeding have not shown an
      increased risk of thrombosis with tranexamic acid. In practice, as of early 2013,
      the harm-benefit balance of tranexamic acidis favourable in severe traumatic
      bleeding. But when bleeding is not life-threatening, the thrombotic risk is too
      poorly documented to justify exposing patients to a plausible and inadequately
      evaluated risk.

PMID- 23951594
TI  - Quetiapine and cardiac muscle disorders.
AB  - Several detailed case reports have described cardiac muscle disorders
      (cardiomyopathy and myocarditis) in patients treated with quetiapine, some of
      which have been fatal. The symptoms included shortness of breath and oedema. The
      disorders sometimes resolved on withdrawal of quetiapine. Quetiapine is
      chemically similar to clozapine and olanzapine, which are known to sometimes
      provoke this type of adverse effect. In practice, a patient who develops dyspnoea
      or other signs of heart failure during quetiapine therapy may benefit if the
      drug's role is recognised and quetiapine withdrawn.

PMID- 23951595
TI  - Exposure to benfluorex: left heart valve disease very common.

PMID- 23951596
TI  - Methylphenidate: trismus.

PMID- 23951597
TI  - SSRI antidepressants: brain haemorrhage.

PMID- 23951598
TI  - Do not use drugs to prevent onset of lactation. Relieve the discomfort and wait.
AB  - Breast-feeding is not advisable in certain situations and some women do not want
      to breast-feed. If the woman does not breast-feed, lactation ceases after one or
      two weeks. Where does the evaluation of methods used to prevent onset of
      lactation stand in 2012? To answer this question, we reviewed the available
      evidence, based on the standard Prescrire methodology. Among the physical methods
      sometimes proposed, breast binding causes greater discomfort than wearing a bra.
      Dopamine agonists, such as bromocriptine, are effective in inhibiting lactation.
      But the serious, mainly cardiovascular, adverse effects they provoke are
      disproportionate to the discomfort they prevent.These drugs are best avoided.
      High doses of oestrogens inhibit lactation, but the risk of thromboembolism they
      pose is unreasonable in the postpartum setting. Neither diuretics nor homeopathy
      have been shown to have any tangible efficacy against the discomfort associated
      with onset of lactation. In practice, a standard analgesic such as paracetamol
      generally eases the few days of discomfort or pain associated with the onset of
      lactation. Wearing a bra is risk-free and sometimes provides relief. Breast
      discomfort, however intense, does not justify exposing women to the serious
      adverse effects linked to postpartum administration of dopamine agonists or
      oestrogens.

PMID- 23951599
TI  - Trauma and severe bleeding. Tranexamic acid within one hour to reduce mortality.
AB  - Tranexamic acid, an antifibrinolytic agent, reduces postoperative transfusion
      requirements but carries a poorly documented risk of thrombosis. Does tranexamic
      acid reduce mortality among victims of severe traumatic bleeding? To answer this
      question, we conducted a review of the literature, using the standard Prescrire
      methodology. The Crash-2 trial compared the impact of tranexamic acid versus
      placebo on overall mortality in 20 211 trauma victims with either severe bleeding
      or a high risk of severe bleeding. Overall mortality at 4 weeks was 14.5% in the
      tranexamic acid group versus 16% in the placebo group (p = 0.004); on average,
      one death was prevented when about 67 patients were treated with tranexamic acid.
      A statistically significant reduction in bleeding-related mortality was observed
      when tranexamic acid was given within 1 hour after injury. The benefit appeared
      to decline over time, and when treatment began more than 3 hours after injury, it
      appeared to increase the risk of death due to bleeding. In this trial, the effect
      of tranexamic acid on overall mortality among patients with traumatic head injury
      is uncertain. Rapid intravenous injection of tranexamic acid can cause
      hypotension. Cases of thrombosis have also been reported. In 2011, the FDA warned
      of a risk of convulsions linked to high intravenous doses of this drug. In
      practice, intravenous tranexamic acid infusion has a favourable harm-benefit
      balance in patients with severe traumatic bleeding, especially when treatment
      begins less than 1 hour after injury, in which case it reduces mortality at 4
      weeks.

PMID- 23951601
TI  - Meals: a very effective gift.

PMID- 23951600
TI  - Hepatitis C and interferon: fewer cases of liver cancer.
AB  - Data on the risk of hepatocellular carcinoma in interferon-treated patients with
      chronic hepatitis C participating in placebo-controlled trials of interferon have
      been published after 3 to 9 years of follow-up. Among patients with chronic
      hepatitis C and either fibrosis or cirrhosis, interferon greatly reduced the risk
      of hepatocellular carcinoma after 8 years or more, especially when viral load was
      below the limit of detection.

PMID- 23951602
TI  - Adolescent sexual risk-taking in a psychosocial context: implications for HIV
      prevention.

PMID- 23951603
TI  - The new politics of the Affordable Care Act (ACA).

PMID- 23951604
TI  - Community-level HIV stigma is a public health threat.

PMID- 23951605
TI  - Challenges to accessing medical care:  the black youth perspective.

PMID- 23951606
TI  - How do infant feeding practices impact HIV transmission?

PMID- 23951608
TI  - [A course of care adapted to the needs of the patient].

PMID- 23951607
TI  - Authors' reply.

PMID- 23951609
TI  - [Strategies for combatting infectious disease].

PMID- 23951610
TI  - [Shaping future health care professionals].

PMID- 23951611
TI  - [What will be the role of nurses in vaccination?].

PMID- 23951612
TI  - [New tools for balanced nutrition in diabetes].

PMID- 23951613
TI  - [Two products for the management of venous leg ulcers].

PMID- 23951614
TI  - [Provision of emergency care].

PMID- 23951615
TI  - [Emergency medical service in practice].
AB  - Specific to France and recognised worldwide, the SAMU (emergency medical service)
      is an essential element of French public health care. The concept is to take the
      hospital outside its walls and treat the person on the spot and in as short a
      time as possible. The emergency medical service has a multidisciplinary approach.

PMID- 23951616
TI  - [Medical-psychological emergency unit].

PMID- 23951617
TI  - [Myocardial infarction, a condition to treat without delay].
AB  - Acute myocardial infarction is a frequent manifestation and is associated with
      high mortality and morbidity rates. Minimizing the time between the onset of
      symptoms and myocardial reperfusion is key to successful treatment. Pre-hospital
      medical treatment is associated with improved clinical outcomes.

PMID- 23951618
TI  - [Early management of cerebrovascular accidents].
AB  - A cerebrovascular accident requires urgent diagnosis and treatment.The management
      of a stroke must be early and adapted in order to improve the overall clinical
      outcome and lower the risk of mortality.

PMID- 23951619
TI  - [Medical emergencies and sea rescue].
AB  - Military nurses and doctors are on permanent standby to respond to any medical
      emergency which may arise at sea. This atypical form of practice is part of a
      specific organisation, in order to provide optimal, high-quality care in the most
      remote places of the oceans.

PMID- 23951620
TI  - [Organization and management of mountain rescues].
AB  - Mountain rescue is a matter for specialists. Specific training, a model of
      organisation under state control, emergency protocols and information and
      prevention campaigns have helped to improve morbidity and mortality rates in the
      mountains.

PMID- 23951621
TI  - [Disaster medicine, organization and management].
AB  - A disaster situation requires an organised command of the emergency services as
      well as of the treatment of victims and their orientation. The aim is to avoid
      any deterioration in the quality of the emergency care provided to the patients.
      A medical speciality, disaster medicine requires specific training.

PMID- 23951622
TI  - [Emergencies and humanitarian aid in cases of armed conflict].
AB  - The Libyan revolution which began in February 2011 caused a massive influx of
      refugees of different nationalities into Tunisia. A refugee camp was gradually
      set up by the Tunisian authorities in collaboration with civil society and
      international humanitarian organisations. The refugees' health care and emergency
      treatment became a necessity.

PMID- 23951623
TI  - [The management of victims by the medical-psychological emergency unit].
AB  - Integrated into the emergency medical assistance system, the medical
      psychological emergency cell (CUMP) provides a link between disaster medicine,
      psychiatric emergencies and psychopathology. It is made up of specialized health
      care professionals and volunteers.Theirworkwith victims and professionals is
      immediate as well as medium- and long-term.

PMID- 23951624
TI  - [Training in emergency situations through medical simulation].
AB  - Alongside conventional teaching, simulation is an effective training technique.
      It comprises a series of techniques enabling experiences in real situations to be
      replaced by those in equivalent situations in an immersive and interactive way
      This type of training does not enable errors to be totally avoided, but helps to
      reduce the consequences.

PMID- 23951625
TI  - [The challenges of emergency medicine].

PMID- 23951626
TI  - [Bibliography. Emergency medical services].

PMID- 23951627
TI  - [Critical pathway and the patient information packet].

PMID- 23951628
TI  - Metformin: the unauthorized biography.

PMID- 23951629
TI  - Understanding cardiovascular biomarkers.

PMID- 23951630
TI  - Cooking 101: easy dinners.

PMID- 23951631
TI  - Eating well on a budget.

PMID- 23951632
TI  - Picking the right activity to meet your fitness goals.

PMID- 23951633
TI  - Keeping your feet healthy.

PMID- 23951634
TI  - Yogurt.

PMID- 23951635
TI  - [Lesions of the vulva, fever, chills. You can expect to make this diagnosis more
      frequently again. Primary syphilis].

PMID- 23951636
TI  - [Treatment of chronic patients and additional services].

PMID- 23951637
TI  - [House call - patient not there].

PMID- 23951638
TI  - [How will this affect my practice?].

PMID- 23951639
TI  - [Is this a wise investment?].

PMID- 23951640
TI  - [Constant disputes in general practice. How to diffuse the conflicts].

PMID- 23951641
TI  - [Who must have tuberculosis screening? Characteristics of risk patients].

PMID- 23951642
TI  - [Differential therapy with the new anticoagulants, 5].

PMID- 23951643
TI  - [Pain therapy: stepchild of geriatrics].

PMID- 23951644
TI  - [Are you communicating properly? (interview by Dr. Beate Schumacher)].

PMID- 23951645
TI  - [No soy for children and men?].

PMID- 23951646
TI  - [Frequent gout attacks during therapy - what can be done?].

PMID- 23951647
TI  - [That is why I am a migrant].

PMID- 23951648
TI  - [Radeberger instead of lithium].

PMID- 23951649
TI  - [Alternatives to "classical" human medicine education].

PMID- 23951650
TI  - [Resuscitation in the eyes of relatives].

PMID- 23951651
TI  - [Lethal toothpick].

PMID- 23951652
TI  - [Antibiotics for acute bronchitis without benefit].

PMID- 23951653
TI  - [Pseudohernia due to herpes zoster].

PMID- 23951654
TI  - [Point victory for the screening colonoscopy].

PMID- 23951655
TI  - [No increased cancer risk with insulin analogues].

PMID- 23951656
TI  - [Sucked out by worms].

PMID- 23951657
TI  - [CAP is treated intravenously for too long].

PMID- 23951658
TI  - [Travel within and outside Europe - new pathogens on the horizon?].

PMID- 23951659
TI  - [Viral souvenirs from travels - also important when not traveling in the
      tropics].

PMID- 23951660
TI  - [Malaria - update 2013].

PMID- 23951661
TI  - [What should a travel health kit contain?].

PMID- 23951662
TI  - [Effectiveness of analgesic combinations in the self-medication].

PMID- 23951663
TI  - [Nicotine withdrawal - don't leave your COPD patients alone].

PMID- 23951664
TI  - [Update nephrology 2013].

PMID- 23951665
TI  - [Non medical treatments of hypertension].

PMID- 23951666
TI  - [Diabetes experts evaluate therapy with modern insulin analogs positively
      (interview by Dr. Silke Wedekind)].

PMID- 23951667
TI  - [How do we build the future?].

PMID- 23951668
TI  - [The borderline personality disorder in primary care].
AB  - Borderline personality disorder is increasingly common in today's society. There
      is approaching the problem of the borderline sick primary care nurse, to achieve
      and promote early detection of risk factors and promote interest in the
      prevention of complications associated with those already diagnosed. Through an
      extensive literature search, we go through the origin of the term until today, to
      finally establish the link with the primary care nursing, in a context of
      symbolic changes, with the addition of the new specialty of nursing family and
      community. Early intervention in patients is very important, the implication of
      the primary care team, an obligation. This article proposes an up-to-date
      knowledge of the object of study personality disorder, displays the profile of
      the patient, promotes the detection and early intervention and invites reflection
      and involvement of primary care.

PMID- 23951669
TI  - [Experience of fibromyalgia].
AB  - OBJECTIVE: To show the experience of people suffering from fibromyalgia, through
      ethnography and narrative, and a reflection to raise and question the direction
      of professional care. METHODOLOGY: Qualitative, and within this focused
      ethnography, generating information through participant observation and in-depth
      interviews with two women and a man suffering from fibromyalgia, with analysis
      emerging from five units of narrative. RESULTS: Highlight the stress generated in
      the waiting time to diagnosis and the vital break which means the disease, the
      difficulty of sharing with family and friends, the conflict with the health
      system and the limited presence of nurses, the interest to remain active at work
      and personal life, although tightly constrained by the pain and discomfort,
      treatment adherence, aid associations representing, and thinking the present and
      little for the future. CONCLUSIONS: The diagnosis represents a naming an
      extensive upset while freeing energy of search, the little information that
      accompanies it difficult to handle the uncertainty and move toward a harmonious
      adaptation. The affected people follow the prescribed treatment, showing great
      interest in staying active and their pain or discomfort hamper it, they live
      intensely the present and think little for the future. Some nurses taking care
      professional current care models are suitable for individualized care in a
      chronic and complex illness, and the narrative is a strategy to the knowledge of
      the illness experience.

PMID- 23951670
TI  - [Pain in the elderly].
AB  - Pain leads to unpleasant sensory or emotional experience for any individual. In
      the elderly, given their biopsychosocial characteristics, the pain requires a
      specific approach, different from other age groups: this is the objective of this
      article, which dealt with the different types of pain, the assessment and
      treatment of the same.

PMID- 23951671
TI  - [Importance of the school nurse's role in the Canary Islands schools].
AB  - Today there are more and more children with chronic diseases or physical
      conditions that regularly attend schools. This study aims to identify the
      importance of school centers' directors attribute to the school nurse. It has
      been decided to make a cross-sectional study. So, it has been to sent by e-mail a
      questionnaire of 20 questions to 635 schools, receiving 209 completed. 65.6% of
      children in schools have required drugs administration. In 59.3% of schools,
      teachers have attended at one time any health problems (acute or chronic) of
      children. 98.1% of schools know the health problems of the students who is in
      charge. The most common health problem among children in schools were food
      allergies, followed by asthma, diabetes and epilepsy. 67% of school centers'
      directors know the guide attention to health emergencies in schools.

PMID- 23951672
TI  - [The functional assessment as comprehensive geriatric assessment axis].
AB  - The comprehensive geriatric assessment (VGI) is a diagnostic process dynamic,
      structured, multidimensional and interdisciplinary to detect problems and needs
      of older people to develop an intervention strategy, although scientific evidence
      should not apply to all groups elderly. The VGI is developed by an
      interdisciplinary team, which plays a key role nursing. The framework nurse and
      nursing conceptual models, especially the 11 functional health patterns, enable
      the multidimensional assessment and subsequent intervention. The VGI covers four
      areas, clinic, mental, social and functional, although its axis, its importance
      and globalization concept is functional assessment. For this we have the history,
      physical examination and a series of specific instruments, geriatric assessment
      scales. They are a complement to, not only the VGI axis.

PMID- 23951673
TI  - [Needs and support networks of informal caregivers of people with Parkinson's
      disease: a literature review].
AB  - OBJECTIVE: To develop knowledge about the needs of informal caregivers of people
      with Parkinson's disease and analyze the evidence of social support interventions
      to meet these needs. BACKGROUND: Parkinson's disease is a highly prevalent
      disease that causes a range of physical-psycho-social-emotional needs in the
      patient and his/her informal caregiver. Although quality of life and wellbeing of
      informal caregivers affect the care they provide patients with, their needs are
      not clearly represented in the literature. METHODS: A non systematic literature
      review of the evidence available in databases: PubMed, Medline, PsycINFO, CINAHL,
      Cochrane Library, BIREME and CUIDEN, published in the period 2001-2011. In
      addition, a manual search by reviewing the table of contents of the last 5 years
      in relevant journals related to the topic of this work and the snowballing
      technique have taken place. RESULTS: Informal caregivers have lots of needs that
      are not covered by the social support they receive. Caregivers' most demanded
      types of support are respite care, financial and socioemotional support, and
      coordination of continued multidisciplinary care. Precisely, these are rarely
      offered by professionals. CONCLUSIONS: The results of this review evidence that
      health professionals must provide social support to ensure holistic and
      personalized care to patients, and also to ensure caregivers' health as needed.

PMID- 23951674
TI  - [The responsibilities of pediatric nurses have increased significantly].

PMID- 23951675
TI  - [The Pflegezeitschrift has accompanied a wound nursing expert in ambulatory care.
      "Nurses have have a lot to say!"].

PMID- 23951676
TI  - [Steinbruck promises 125,000 new positions for nursing care].

PMID- 23951677
TI  - [The effects of inpatient stay on the experience and behavior of children and the
      role of nursing. Almost as on the playground?].

PMID- 23951678
TI  - [Postpartum psychiatric diseases: a topic for health and pediatric nursing. The
      goal is a successful mother-child relationship].

PMID- 23951679
TI  - [Family health and pediatric nursing in child day care centers and family
      centers. An important building block in public welfare].

PMID- 23951680
TI  - [Risk management in the operating room. Promoting a constructive error culture].

PMID- 23951681
TI  - [Quality of life - a trendy expression in nursing and health. Not just the
      outcome of nursing interventions].

PMID- 23951682
TI  - [Understanding communication and interaction in nursing care - 2. Cooperation at
      the patient bedside].

PMID- 23951683
TI  - [Training parents after the birth of their child reduces the risk of abusive head
      trauma].

PMID- 23951684
TI  - [Counseling in nursing care with the "Wittener guidelines". Not losing sight of
      oneself].

PMID- 23951685
TI  - ["And there are always enough 'promo leaflets'". A qualitative study on the
      situation of leg ulcer patients and their needs in regard to patient education].
AB  - Chronic leg ulcers influence the daily lives of patients. Besides the burden of
      therapy, research results in the field of quality of life indicate constraints in
      the psychological, physiological, occupational and social parts of life. In order
      to take an active role in coping with the chronic disease, patients need
      knowledge and information that account for individual needs. Therefore our study
      had the objective to describe the lived experience of patients with leg ulcer and
      their corresponding needs for patient education. We used a qualitative study
      design. In a first step we made five narrative interviews. In a second step we
      made seven interviews using an interview guide that was based on results of the
      narrative interviews. Participants were recruited in two regions in Germany via
      two specialist practices and a hospital. We used a purposeful sampling strategy
      in order to account for the heterogenity of the patient group. Data was analysed
      using the content analysis approach by Mayring. Our analysis identified 4
      interconnected main categories: living with the illness, experiences of wound
      care, being an expert, and educational needs. Patients are trying to integrate
      their illness into daily life and maximize their independence. They prefer
      individual counselling during regulartreatment to group counselling or meetings
      with other leg ulcer patients. Overall the described problems and solutions
      illustrate the complexities of the disease and its care.

PMID- 23951686
TI  - [Pedagogue tests nursing practice references of Prof. Ekkehard Marschelke. Self
      efficacy is a powerful agent].

PMID- 23951687
TI  - [Relationship marketing in health care facilities. "Have you snacked yet, Herr
      Mayer?"].

PMID- 23951688
TI  - [Child welfare risk. What nurses can do. Between confidentiality and mandatory
      reporting].

PMID- 23951689
TI  - [An overview. The federal child protection law and its relevance for family,
      health and pediatric nurses].

PMID- 23951690
TI  - [Dehydration in children. Recognizing the risk of exicosis].

PMID- 23951691
TI  - Magnetic resonance imaging findings in pediatric bilateral vocal fold
      dysfunction.
AB  - OBJECTIVES: We studied the findings of brain magnetic resonance imaging (MRI) in
      infants with idiopathic congenital bilateral vocal fold dysfunction (CBVFD).
      METHODS: We performed a retrospective investigation of a case series. RESULTS: We
      identified 26 children (14 male, 12 female) over 11 years. Three children were
      excluded. Thirteen patients required airway interventions, including continuous
      positive airway pressure (4 patients), endotracheal intubation (1), and
      tracheostomy (8). The findings on brain MRI were abnormal in 8 patients (35%).
      Tracheostomy was required in 3 patients (38%) with abnormal MRI findings, as
      compared with 5 of 15 patients (33%) with normal MRI findings. The MRI
      abnormalities involved evidence of white matter injury (2), abnormal white matter
      signal (1), subdural blood (3), cerebral swelling (1), and perisylvian
      polymicrogyria (1). The cranial ultrasound findings were abnormal in 4 of 11
      patients. The MRI findings were abnormal in 2 of 7 children in whom the cranial
      ultrasound findings were normal, and in 2 of the 4 patients in whom the cranial
      ultrasound findings were abnormal. CONCLUSIONS: The MRI abnormalities were
      nonspecific; however, they may indicate unrecognized perinatal intracranial
      injury as being related to CBVFD. In addition, MRI may reveal an underlying
      structural brain anomaly. Cranial ultrasound has poor sensitivity and
      specificity. Hence, MRI should be considered as part of the routine assessment of
      neonates with CBVFD.

PMID- 23951692
TI  - Comparison between dexmedetomidine and remifentanil for controlled hypotension
      and recovery in endoscopic sinus surgery.
AB  - OBJECTIVES: We compared the efficacy of dexmedetomidine and remifentanil
      hydrochloride in intraoperative field conditions and recovery during endoscopic
      sinus surgery. METHODS: Sixty-six patients (American Society of Anesthesiologists
      physical status I and II) scheduled for elective endoscopic sinus surgery were
      enrolled in this prospective, double-blinded, randomized study. The patients were
      randomly assigned to two groups. Propofol, 2 to 2.5 mg/kg, was administered to
      both groups to induce anesthesia, which was maintained with desflurane. One group
      received dexmedetomidine 1 microg/kg over 10 minutes at anesthesia induction,
      followed by 0.4 to 0.8 microg/kg per hour infusion during maintenance, whereas
      the other group received remifentanil 1 microg/kg over 1 minute at anesthesia
      induction, followed by 0.2 to 0.4 microg/kg per minute infusion during
      maintenance. Surgical conditions, hemodynamic parameters, intraoperative blood
      loss, time to extubation, sedation, and pain in the postanesthesia care unit
      (PACU) were recorded. RESULTS: There were no significant differences between the
      two groups with respect to surgical field conditions, blood loss, or extubation
      time. The sedation score (Modified Observer's Assessment of Alertness/Sedation)
      in the PACU was significantly lower in the dexmedetomidine group than in the
      remifentanil group (p < 0.001). No differences were found in total blood loss,
      surgical field conditions, hemodynamic parameters, time to extubation, or pain in
      the PACU when the two groups were compared (p > 0.05). CONCLUSIONS: Although
      remifentanil and dexmedetomidine both enabled hypotensive anesthesia and good
      intraoperative fields for endoscopic sinus surgery, recovery was faster with
      remifentanil than with dexmedetomidine in the immediate postoperative period.

PMID- 23951693
TI  - Subglottic laryngeal closure: a unique modified method of laryngotracheal
      separation to prevent aspiration.
AB  - OBJECTIVES: Laryngotracheal separation (LTS) is an ideal surgical method for
      intractable aspiration; however, the oral side of the tracheal stump can easily
      disintegrate. Therefore, we developed a modified LTS method. We performed
      subglottic laryngeal closure (SGLC) as a new surgical method and evaluated the
      outcomes. METHODS: We retrospectively analyzed the medical records of 36 patients
      (28 male and 8 female; 15 to 91 years of age) who underwent SGLC between 2007 and
      2011 at Tottori University Hospital, Japan. Operative data (operative time,
      intraoperative bleeding, and time to drain removal), outcomes (aspiration and
      changes in nutritional status), and complications with regard to the surgical
      method were examined. The occurrence of a subcutaneous proximal laryngeal stump
      fistula was evaluated by videofluoroscopy. RESULTS: The SGLC was performed safely
      in all patients. Fistulization was observed in only 1 of the patients (2.8%), and
      major bleeding after surgery was observed in 1 patient (2.8%). The procedure
      relieved aspiration pneumonia in all patients. CONCLUSIONS: We conclude that SGLC
      is effective for treating and preventing pulmonary aspiration. The incidence of
      postoperative complications, particularly that of subcutaneous fistulas, was very
      low. Therefore, this method may be useful for patients in poor condition.

PMID- 23951694
TI  - Oropharyngeal syphilis among patients infected with human immunodeficiency virus.
AB  - OBJECTIVES: There has been a reemergence of syphilis among men who have sex with
      men over the past decade, especially in patients infected with human
      immunodeficiency virus (HIV). This study was aimed at describing the
      oropharyngeal manifestations of secondary syphilis in HIV-infected patients. We
      also sought to determine the clinical risk factors for the development of
      oropharyngeal syphilitic lesions in patients with secondary syphilis. METHODS: We
      performed an observational, comparative, retrospective study of HIV-infected
      patients who were admitted to a tertiary referral center in Mexico City and who
      had syphilis according to the criteria of the US Centers for Disease Control and
      Prevention. RESULTS: We identified 44 patients with syphilis, 31 of whom had
      secondary syphilis and 9 of whom had oropharyngeal manifestations. Lesions
      involving the anterior tonsillar pillar were the most common, observed in 5
      patients; and tongue lesions were observed in 3 patients. In the patients with
      secondary syphilis, multivariate analysis showed that the development of
      oropharyngeal lesions was not associated with age, CD4 and CD8 cell counts, or
      HIV RNA viral load. CONCLUSIONS: The present work shows that oropharyngeal
      manifestations of secondary syphilis and overlapping stages of syphilis are
      frequent in HIV-infected patients. To the best of our knowledge, this is the
      first comparative study of the oropharyngeal manifestations of syphilis in HIV
      infected patients.

PMID- 23951695
TI  - Salivary concentration of epidermal growth factor in adults with reflux
      laryngitis before and after treatment.
AB  - OBJECTIVES: The diagnosis of laryngopharyngeal reflux (LPR) is controversial.
      There is no correlation between the number of reflux episodes and the severity of
      the inflammatory response at the esophagus or the laryngopharyngeal segment. Some
      authors have suggested that decreased salivary epidermal growth factor (EGF)
      concentrations in patients with gastroesophageal reflux disease and LPR point to
      a breakdown in the local defenses. Our objective was to establish whether
      treatment of the disease influences low salivary EGF concentrations. METHODS: The
      spontaneous whole saliva of 20 adults with LPR was sampled at a tertiary teaching
      hospital before and after a 16-week course of full-dose proton pump inhibitor and
      compared to that of 12 healthy controls. Salivary EGF concentrations were
      established with a commercially available enzyme-linked immunosorbent assay kit.
      RESULTS: Although the mean salivary EGF concentrations were higher before
      treatment than after treatment and control of the disease (25,083 versus 19,359
      pg/mL), this difference was not statistically significant (p = 0.065). The mean
      salivary EGF concentration of healthy control subjects was significantly higher
      (54,509 pg/mL; p < 0.0001). CONCLUSIONS: Both before and after treatment,
      patients with reflux laryngitis present lower salivary EGF concentrations than
      healthy control subjects, suggesting a primary deficit in their protective
      mechanisms.

PMID- 23951696
TI  - Novel method for laryngotracheal reconstruction: combining single- and double
      stage techniques.
AB  - OBJECTIVES: Traditional open techniques for laryngotracheal reconstruction are
      either single- or double-stage procedures. Some patients may benefit from the
      presence of a long, single-tube stent, such as an endotracheal tube, but their
      predicted need for a 2-stage procedure and a persistent tracheostomy is high. We
      describe a novel technique for airway reconstruction that combines the methods of
      both single- and double-stage procedures. METHODS: We present a retrospective
      review of 4 patients. All patients underwent laryngotracheal reconstruction by a
      single surgeon. After the operation, the airway was stented with nasotracheal
      intubation. A small stent, fashioned from an endotracheal tube, was placed in the
      tracheostoma to keep it patent. The patients subsequently underwent extubation
      and replacement of the tracheostomy tube. RESULTS: The study included 1 patient
      with grade 4 subglottic stenosis, 2 patients with grade 3 subglottic stenosis,
      and 1 patient with a posterior glottic scar. All were tracheostomy tube
      dependent. Serial bronchoscopy was used to follow the patients for a minimum of 9
      months after the operation. All 4 patients have since met the criteria for
      decannulation. CONCLUSIONS: This hybrid reconstruction merges the advantages of
      both the single- and double-stage procedures. It adds versatility to the surgical
      toolbox for airway reconstruction.

PMID- 23951697
TI  - Thyroid hormone replacement therapy, surveillance ultrasonography, and fine
      needle aspiration after hemithyroidectomy.
AB  - OBJECTIVES: We undertook a retrospective analysis of a single surgeon's
      experience at a tertiary care teaching hospital to determine the rates of
      surveillance ultrasound, fine-needle aspiration (FNA), and the need for thyroid
      hormone replacement therapy (THRT) after hemithyroidectomy. METHODS: The study
      population comprised 120 consecutive patients who underwent hemithyroidectomy by
      one surgeon from January 2008 to June 2011. The medical records were reviewed for
      preoperative and postoperative calcium levels, fiberoptic direct laryngoscopy
      examination of vocal fold mobility, postoperative complications, final pathology,
      and postoperative follow-up. RESULTS: Fifteen patients required completion
      thyroidectomy for malignancy and were excluded from the surveillance analysis. Of
      the remaining 105 patients, 10 (9.5%) required postoperative THRT. The likelihood
      for THRT was significantly associated with increased age (p = 0.01) and the
      presence of thyroiditis (p = 0.04). Other factors, such as gender, body mass
      index, residual thyroid volume, and presence of contralateral lobe nodules, were
      not significantly associated with this likelihood (p > 0.05). Twenty-three
      patients (21.9%) were followed with surveillance ultrasound, of whom 12 (11.4%)
      underwent FNA for nodule(s) in the contralateral lobe. Seventy-eight percent of
      patients did not require any long-term postoperative surveillance. There were no
      instances of permanent recurrent laryngeal nerve injury or hypoparathyroidism.
      CONCLUSIONS: Hemithyroidectomy is an effective and efficient option for the
      management of benign and suspicious thyroid nodules. However, patients of
      increased age and/or with thyroiditis are at higher risk for postoperative
      hypothyroidism, and should be counseled to consider total thyroidectomy to avoid
      the need for long-term surveillance and the possible need for a second operation.

PMID- 23951698
TI  - Malignant transformation of respiratory papillomatosis in a solid-organ
      transplant patient: case report and literature review.
AB  - We report the case of a 77-year-old non-smoker and non-drinker with a solid-organ
      transplant who had malignant transformation of respiratory papillomatosis 3 years
      after the initial diagnosis of this benign lesion. This is the first case
      reported in the literature of malignant transformation of respiratory
      papillomatosis in a solid-organ transplant patient. Virus-associated cutaneous
      cancers occur more frequently and aggressively in solid-organ transplant
      patients. There may be a higher rate of malignant transformation of respiratory
      papillomatosis in immunosuppressed patients, as this is a virus-associated
      disease. Closer observation, airway evaluation with laryngoscopy and
      tracheobronchoscopy, and interval biopsies of immunosuppressed patients with
      respiratory papillomatosis is recommended.

PMID- 23951699
TI  - Chronic otorrhea caused by myospherulosis in the middle ear after tympanoplasty.
AB  - OBJECTIVES: Myospherulosis is a foreign body reaction induced by the application
      of oil-based ointments. Myospherulosis in the ear is extremely rare. Only 4 cases
      have been described, all of which occurred after (repeated) mastoid surgery.
      METHODS: We present a case of persistent otorrhea and conductive hearing loss
      caused by myospherulosis in the middle ear following tympanoplasty. RESULTS: The
      patient underwent revision middle ear surgery with removal of abnormally thick,
      pale tissue in the middle ear. Histology showed a foreign body reaction with
      signs of myospherulosis. CONCLUSIONS: Myospherulosis is a very rare complication
      of the use of oil-based ointments. Surgeons should be aware that these products
      might cause a foreign body reaction leading to myospherulosis. In patients who
      have chronic otorrhea after previous mastoid or middle ear surgery,
      myospherulosis should be considered in the differential diagnosis.

PMID- 23951700
TI  - Efficacy of dexpanthenol for pediatric post-tonsillectomy pain and wound healing.
AB  - OBJECTIVES: We evaluated the efficacy of dexpanthenol in managing pediatric post
      tonsillectomy pain and wound healing and sought to discover which of two surgical
      tonsillectomy techniques provides better healing and less postoperative pain.
      METHODS: One hundred twenty patients who underwent tonsillectomy were equally
      randomized to thermal welding and cold dissection groups. Dexpanthenol pastilles
      were given to half of each group. Postoperative throat pain was determined with a
      visual analog scale on the 1st, 3th, 7th, and 14th days, and mucosal healing
      patterns were assessed on the 7th and 14th days. RESULTS: Regardless of surgical
      technique, post-tonsillectomy throat pain was significantly less in the
      dexpanthenol groups than in the placebo groups (p < 0.05), and tonsillar wound
      healing was significantly better in the dexpanthenol groups than in the placebo
      groups (p < 0.05). When a comparison was made with regard to surgical technique,
      wound healing was significantly better in the cold dissection group (p < 0.05),
      whereas postoperative throat pain was less in the thermal welding group (p <
      0.05). CONCLUSIONS: Postoperative administration of dexpanthenol significantly
      accelerates the wound healing process and decreases tonsillectomy-related pain
      complaints.

PMID- 23951701
TI  - Etanercept prevents decrease of cochlear blood flow dose-dependently caused by
      tumor necrosis factor alpha.
AB  - OBJECTIVES: Tumor necrosis factor alpha (TNF-alpha) is a mediator of inflammation
      and microcirculation in the cochlea. This study aimed to quantify the effect of a
      local increase of TNF-alpha and study the effect of its interaction with
      etanercept on cochlear microcirculation. METHODS: Cochlear lateral wall vessels
      were exposed surgically and assessed by intravital microscopy in guinea pigs in
      vivo. First, 24 animals were randomly distributed into 4 groups of 6 each.
      Exposed vessels were superfused repeatedly either with 1 of 3 different
      concentrations of TNF-alpha (5.0, 0.5, and 0.05 ng/mL) or with placebo (0.9%
      saline solution). Second, 12 animals were randomly distributed into 2 groups of 6
      each. Vessels were pretreated with etanercept (1.0 microg/ mL) or placebo (0.9%
      saline solution), and then treated by repeated superfusion with TNF-alpha (5.0
      ng/mL). RESULTS: TNF-alpha was shown to be effective in decreasing cochlear blood
      flow at a dose of 5.0 ng/mL (p < 0.01, analysis of variance on ranks). Lower
      concentrations or placebo treatment did not lead to significant changes. After
      pretreatment with etanercept, TNF-alpha at a dose of 5.0 ng/mL no longer led to a
      change in cochlear blood flow. CONCLUSIONS: The decreasing effect that TNF-alpha
      has on cochlear blood flow is dose-dependent. Etanercept abrogates this effect.

PMID- 23951702
TI  - Two new polymers as candidates for rhinoplasty allografts: an experimental study
      in a rabbit model.
AB  - OBJECTIVES: This study was performed to evaluate the biocompatibility and tensile
      strength of two new polymeric materials--a polyfluoro ether-modified
      thermoplastic polyurethane urea and a polydimethyl silicone elastomer--in an
      experimental rabbit model. METHODS: The two polymers were implanted inside
      separate subperichondrial pockets created over the auricular cartilages of 12
      rabbits. A control pocket received no implant. After 3 months, the animals were
      painlessly sacrificed, and each site was analyzed histologically for vascular
      congestion, acute and chronic inflammation, and fibrosis in the tissue
      surrounding the implant materials. RESULTS: There were no statistically
      significant differences in vascular congestion, fibrosis, or acute or chronic
      inflammation between the control sites and either implant site. CONCLUSIONS:
      These results suggest that the polymers are well accepted by the tissue and
      remain stable during the entire study period, and that they could be very
      suitable materials for use in nasal reconstruction.

PMID- 23951703
TI  - Estimated losses of plant biodiversity in the United States from historical N
      deposition (1985-2010).
AB  - Although nitrogen (N) deposition is a significant threat to herbaceous plant
      biodiversity worldwide, it is not a new stressor for many developed regions. Only
      recently has it become possible to estimate historical impacts nationally for the
      United States. We used 26 years (1985-2010) of deposition data, with ecosystem
      specific functional responses from local field experiments and a national
      critical loads (CL) database, to generate scenario-based estimates of herbaceous
      species loss. Here we show that, in scenarios using the low end of the CL range,
      N deposition exceeded critical loads over 0.38, 6.5, 13.1, 88.6, and 222.1
      million ha for the Mediterranean California, North American Desert, Northwestern
      Forested Mountains, Great Plains, and Eastern Forest ecoregions, respectively,
      with corresponding species losses ranging from < 1% to 30%. When we ran scenarios
      assuming ecosystems were less sensitive (using a common CL of 10 kg x ha(-1) x
      yr(-1), and the high end of the CL range) minimal losses were estimated. The
      large range in projected impacts among scenarios implies uncertainty as to
      whether current critical loads provide protection to terrestrial plant
      biodiversity nationally and urge greater research in refining critical loads for
      U.S. ecosystems.

PMID- 23951704
TI  - Finely tuned response of native prey to an invasive predator in a freshwater
      system.
AB  - Lack of shared evolutionary history reduces the expectation that native prey will
      detect and respond to invasive predators. Four mechanisms may explain the
      adaptive response that is nevertheless seen in various systems: prey may perceive
      the invasive predator through cue similarity with preexisting predators, cues of
      conspecifics eaten by the invasive predator, a learned response based on
      experience with the invasive predator (e.g., cue association), and cues from the
      invasive predator that are specific to it. We performed laboratory experiments in
      which zooplankton (Daphnia mendotae) responded adaptively to the zooplanktivore
      Bythotrephes longimanus (migrating downward), showed no response to taxonomically
      similar predatory cladocerans, and responded adaptively to more taxonomically
      distant native fish (migrating downward) and native shrimp (migrating upward).
      Conspecific cues associated with Bythotrephes predation actually reduced the
      response of D. mendotae to Bythotrephes. Combined with previous experiments that
      rule out learning, our experiments rule out the first three mechanisms above,
      demonstrating that D. mendotae respond to cues specific to and produced directly
      by Bythotrephes. This finely tuned response may be retained from an ancestral
      species that coevolved with Bythotrephes in its native range, or may have rapidly
      evolved due to strong selection by the invasive predator.

PMID- 23951705
TI  - Practical guidance on characterizing availability in resource selection functions
      under a use-availability design.
AB  - Habitat selection is a fundamental aspect of animal ecology, the understanding of
      which is critical to management and conservation. Global positioning system data
      from animals allow fine-scale assessments of habitat selection and typically are
      analyzed in a use availability framework, whereby animal locations are contrasted
      with random locations (the availability sample). Although most use-availability
      methods are in fact spatial point process models, they often are fit using
      logistic regression. This framework offers numerous methodological challenges,
      for which the literature provides little guidance. Specifically, the size and
      spatial extent of the availability sample influences coefficient estimates
      potentially causing interpretational bias. We examined the influence of
      availability on statistical inference through simulations and analysis of
      serially correlated mule deer GPS data. Bias in estimates arose from incorrectly
      assessing and sampling the spatial extent of availability. Spatial
      autocorrelation in covariates, which is common for landscape characteristics,
      exacerbated the error in availability sampling leading to increased bias. These
      results have strong implications for habitat selection analyses using GPS data,
      which are increasingly prevalent in the literature. We recommend that researchers
      assess the sensitivity of their results to their availability sample and, where
      bias is likely, take care with interpretations and use cross validation to assess
      robustness.

PMID- 23951706
TI  - Integrated modeling of bilateral photo-identification data in mark-recapture
      analyses.
AB  - When natural marks provide sufficient resolution to identify individual animals,
      noninvasive sampling using cameras has a number of distinct advantages relative
      to "traditional" mark-recapture methods. However, analyses from photo
      identification records often pose additional challenges. For example, it is often
      unclear how to link left- and right-side photos to the same individual, and
      previous studies have primarily used data from just one side for statistical
      inference. Here we describe how a recently developed statistical method can be
      adapted for integrated mark-recapture analyses using bilateral photo
      identification records. The approach works by assuming that the true encounter
      history for each animal is a latent (unobserved) realization from a multinomial
      distribution. Based on the type of photo encounter (e.g., right, left, or both
      sides), the recorded (observed) encounter histories can only arise from certain
      combinations of these latent histories. In this manner, the approach properly
      accounts for uncertainty about the true number of distinct animals observed in
      the study. Using a Markov chain Monte Carlo sampling procedure, we conduct a
      small simulation study to show that this approach has reasonable properties and
      outperforms other methods. We further illustrate our approach by estimating
      population size from bobcat photo-identification records. Although motivated by
      bilateral photo-identification records, we note that the proposed methodology can
      be used to combine and jointly analyze other types of mark-recapture data (e.g.,
      photo and DNA records).

PMID- 23951707
TI  - Estimating abundance while accounting for rarity, correlated behavior, and other
      sources of variation in counts.
AB  - The class of N-mixture models allows abundance to be estimated from repeated,
      point count surveys while adjusting for imperfect detection of individuals. We
      developed an extension of N-mixture models to account for two commonly observed
      phenomena in point count surveys: rarity and lack of independence induced by
      unmeasurable sources of variation in the detectability of individuals. Rarity
      increases the number of locations with zero detections in excess of those
      expected under simple models of abundance (e.g., Poisson or negative binomial).
      Correlated behavior of individuals and other phenomena, though difficult to
      measure, increases the variation in detection probabilities among surveys. Our
      extension of N-mixture models includes a hurdle model of abundance and a beta
      binomial model of detectability that accounts for additional (extra-binomial)
      sources of variation in detections among surveys. As an illustration, we fit this
      model to repeated point counts of the West Indian manatee, which was observed in
      a pilot study using aerial surveys. Our extension of N-mixture models provides
      increased flexibility. The effects of different sets of covariates may be
      estimated for the probability of occurrence of a species, for its mean abundance
      at occupied locations, and for its detectability.

PMID- 23951708
TI  - Multilevel statistical models and the analysis of experimental data.
AB  - Data sets from ecological experiments can be difficult to analyze, due to lack of
      independence of experimental units and complex variance structures. In addition,
      information of interest may lie in complicated contrasts among treatments, rather
      than direct output from statistical tests. Here, we present a statistical
      framework for analyzing data sets containing non-independent experimental units
      and differences in variance among treatments (heteroscedasticity) and apply this
      framework to experimental data on interspecific competition among three tadpole
      species. Our framework involves three steps: (1) use a multilevel regression
      model to calculate coefficients of treatment effects on response variables; (2)
      combine coefficients to quantify the strength of competition (the target
      information of our experiment); and (3) use parametric bootstrapping to calculate
      significance of competition strengths. We repeated this framework using three
      multilevel regression models to analyze data at the level of individual tadpoles,
      at the replicate level, and at the replicate level accounting for
      heteroscedasticity. Comparing results shows the need to correctly specify the
      statistical model, with the model that accurately accounts for heteroscedasticity
      leading to different conclusions from the other two models. This approach gives a
      single, comprehensive analysis of experimental data that can be used to extract
      informative biological parameters in a statistically rigorous way.

PMID- 23951709
TI  - Symmetry breaking in ecological systems through different energy efficiencies of
      juveniles and adults.
AB  - Ontogenetic development is a fundamental aspect of the life history of all
      organisms and has major effects on population and community dynamics. We
      postulate a general conceptual framework for understanding these effects and
      claim that two potential energetics bottlenecks at the level of the individual
      organism--the rate by which it develops and the rate by which it reproduces--form
      a fundamental route to symmetry-breaking in ecological systems, leading to
      ontogenetic asymmetry in energetics. Unstructured ecological theory, which
      ignores ontogenetic development, corresponds to a limiting case only, in which
      mass-specific rates of biomass production through somatic growth and
      reproduction, and biomass loss through mortality, are independent of body size
      (ontogenetic symmetry). Ontogenetic symmetry results in development and
      reproduction being limited to the same extent by food density. In all other
      cases, symmetry-breaking occurs. Ontogenetic asymmetry results in increases in
      juvenile, adult, or even total biomass in response to mortality. At the community
      level, this gives rise to alternative stable states via predator-induced shifts
      in prey size distributions. Ontogenetic asymmetry furthermore leads to two
      distinct types of cycles in population dynamics, depending on whether development
      or reproduction is most energy limited. We discuss the mechanisms giving rise to
      these phenomena and the empirical support for them. We conclude that the concepts
      of ontogenetic symmetry and ontogenetic asymmetry form a novel and general
      organizing principle on which future ecological theory should be developed.

PMID- 23951710
TI  - Predicting invertebrate herbivory from plant traits: polycultures show strong
      nonadditive effects.
AB  - Plant functional traits affect the capacity of herbivores to find, choose, and
      consume plants. However, in a community composed of different plant species, it
      is unclear what proportion of herbivory on a focal plant is explained by its own
      traits and which is explained by the characteristics of the surrounding
      vegetation (i.e., nonadditive effects). Moreover, nonadditive effects could be
      positive or negative, and it is not known if they are related to community
      properties such as diversity. To quantify nonadditive effects, we developed four
      different additive models based on monoculture herbivory rates or plant traits
      and combined them with measurements of standing invertebrate herbivore damage
      along an experimental plant diversity gradient ranging from monocultures to 60
      species mixtures. In all four models, positive nonadditive effects were detected,
      i.e., herbivory levels were higher in polycultures than what was expected from
      monoculture data, and these effects contributed up to 25% of the observed
      variance in herbivory. Importantly, the nonadditive effects, which were defined
      as the deviance of the models' predictions from the observed herbivory, were
      positively correlated with the communities' plant species richness. Consequently,
      interspecific interactions appear to have an important impact on the levels of
      herbivory of a community. Identifying those community properties that capture the
      effects of these interactions is a next important challenge for our understanding
      of how the environment interacts with plant traits to drive levels of herbivory.

PMID- 23951711
TI  - Ecosystem engineers on plants: indirect facilitation of arthropod communities by
      leaf-rollers at different scales.
AB  - Ecosystem engineering is a process by which organisms change the distribution of
      resources and create new habitats for other species via non-trophic interactions.
      Leaf-rolling caterpillars can act as ecosystem engineers because they provide
      shelter to secondary users. In this study, we report the influence of leaf
      rolling caterpillars on speciose tropical arthropod communities along both
      spatial scales (leaf-level and plant-level effects) and temporal scales (dry and
      rainy seasons). We predict that rolled leaves can amplify arthropod diversity at
      both the leaf and plant levels and that this effect is stronger in dry seasons,
      when arthropods are prone to desiccation. Our results show that the abundance,
      richness, and biomass of arthropods within several guilds increased up to 22-fold
      in naturally and artificially created leaf shelters relative to unaltered leaves.
      These effects were observed at similar magnitudes at both the leaf and plant
      scales. Variation in the shelter architecture (funnel, cylinders) did not
      influence arthropod parameters, as diversity, abundance, orbiomass, but rolled
      leaves had distinct species composition if compared with unaltered leaves. As
      expected, these arthropod parameters on the plants with rolled leaves were on
      average approximately twofold higher in the dry season. Empty leaf rolls and
      whole plants were rapidly recolonized by arthropods over time, implying a fast
      replacement of individuals; within 15-day intervals the rolls and plants reached
      a species saturation. This study is the first to examine the extended effects of
      engineering caterpillars as diversity amplifiers at different temporal and
      spatial scales. Because shelter-building caterpillars are ubiquitous organisms in
      tropical and temperate forests, they can be considered key structuring elements
      for arthropod communities on plants.

PMID- 23951712
TI  - Life-history traits and landscape characteristics predict macro-moth responses to
      forest fragmentation.
AB  - How best to manage forest patches, mitigate the consequences of forest
      fragmentation, and enable landscape permeability are key questions facing
      conservation scientists and managers. Many temperate forests have become
      increasingly fragmented, resulting in reduced interior forest habitat, increased
      edge habitats, and reduced connectivity. Using a citizen science landscape-scale
      mark-release-recapture study on 87 macro-moth species, we investigated how both
      life-history traits and landscape characteristics predicted macro-moth responses
      to forest fragmentation. Wingspan, wing shape, adult feeding, and larval feeding
      guild predicted macro-moth mobility, although the predictive power of wingspan
      and wing shape depended on the species' affinity to the forest. Solitary trees
      and small fragments functioned as "stepping stones," especially when their
      landscape connectivity was increased, by being positioned within hedgerows or
      within a favorable matrix. Mobile forest specialists were most affected by forest
      fragmentation: despite their high intrinsic dispersal capability, these species
      were confined mostly to the largest of the forest patches due to their strong
      affinity for the forest habitat, and were also heavily dependent on forest
      connectivity in order to cross the agricultural matrix. Forest fragments need to
      be larger than five hectares and to have interior forest more than 100 m from the
      edge in order to sustain populations of forest specialists. Our study provides
      new insights into the movement patterns of a functionally important insect group,
      with implications for the landscape-scale management of forest patches within
      agricultural landscapes.

PMID- 23951713
TI  - A role for indirect facilitation in maintaining diversity in a guild of African
      acacia ants.
AB  - Determining how competing species coexist is essential to understanding patterns
      of biodiversity. Indirect facilitation, in which a competitively dominant species
      exerts a positive effect on one competitor by more strongly suppressing a third,
      shared competitor, is a potentially potent yet understudied mechanism for
      competitive coexistence. Here we provide evidence for indirect facilitation in a
      guild of four African Acacia ant species that compete for nesting space on the
      host plant Acacia drepanolobium, showing that a competitively dominant acacia ant
      species indirectly creates establishment opportunities for the most subordinate
      species that may help to maintain diversity. Using long-term observational data
      and field experiments, we demonstrate that the competitively dominant ant species
      outcompetes two competitively intermediate species, while tolerating colonies of
      the subordinate competitor; this creates opportunities for local colonization and
      establishment of colonies of the subordinate species within the dominant species'
      territories. Host plants occupied by this subordinate species are then more
      likely to be colonized by the intermediate species, which in turn are more likely
      to be displaced by the dominant species. This process has the potential to
      generate a cyclical succession of ant species on host trees, contributing to
      stable coexistence within this highly competitive community.

PMID- 23951714
TI  - A direct test of nitrogen and phosphorus limitation to net primary productivity
      in a lowland tropical wet forest.
AB  - Experimental evidence for limitation of net primary productivity (NPP) by
      nitrogen (N) or phosphorus (P) in lowland tropical forests is rare, and the
      results from the few existing studies have been inconclusive. To directly test if
      N or P limit NPP in a lowland tropical wet forest in Costa Rica, we conducted a
      full factorial fertilization experiment (4 treatments x 6 replicates in 30 x 30 m
      plots). We focused on the influence of tree size and taxa on nutrient limitation,
      because in these forests a wide variety of tree functional traits related to
      nutrient acquisition and use are likely to regulate biogeochemical processes.
      After 2.7 years, a higher percentage of trees per plot increased basal area (BA)
      with P additions (66.45% +/- 3.28% without P vs. 76.88% +/- 3.28% with P), but
      there were no other community-level responses to N or P additions on BA increase,
      litterfall productivity, or root growth. Phosphorus additions resulted in doubled
      stem growth rates in small trees (5-10 cm diameter at breast height (dbh); [P <
      or = 0.01]) but had no effect on intermediate (10-30 cm dbh) or large trees (> 30
      cm dbh). Phosphorus additions also increased the percentage of seedling survival
      from 59% to 78% (P < 0.01), as well as the percentage of seedlings that grew (P =
      0.03), and increased leaf number (P = 0.02). Trees from Pentaclethra macroloba,
      the most abundant species, did not increase growth rates with fertilization (P =
      0.40). In contrast, the most abundant palms (Socratea exorrhiza) had more than
      two times higher stem growth rates with P additions (P = 0.01). Our experiment
      reiterates that P availability is a significant driver of plant processes in
      these systems, but highlights the importance of considering different aspects of
      the plant community when making predictions concerning nutrient limitation. We
      postulate that in diverse, lowland tropical forests "heterogeneous nutrient
      limitation" occurs, not only driven by variability in nutrient responses among
      taxa, but also among size classes and potential functional groups. Heterogeneous
      responses to nutrient additions could lead to changes in forest structure or even
      diversity in the long-term, affecting rates of NPP and thus carbon cycling.

PMID- 23951715
TI  - Seed arrival in tropical forest tree fall gaps.
AB  - Tree deaths open gaps in closed-canopy forests, which allow light to reach the
      forest floor and promote seed germination and seedling establishment. Gap
      dependence of regeneration is an important axis of life history variation among
      forest plant species, and many studies have evaluated how plant species differ in
      seedling and sapling performance in gaps. However, relatively little is known
      about how seed arrival in gaps compares with seed arrival in the understory, even
      though seed dispersal by wind and animals is expected to be altered in gaps. We
      documented seed arrival for the first seven years after gap formation in the
      moist tropical forests of Barro Colorado Island (BCI), Panama, and evaluated how
      the amount and functional composition of arriving seeds compared with understory
      sites. On average, in the first three years after gap formation, 72% fewer seeds
      arrived in gaps than in the understory (207 vs. 740 seeds x m(-2) x yr(-1)). The
      reduction in number of arriving seeds fell disproportionately on animal-dispersed
      species, which suffered an 86% reduction in total seed number, while wind
      dispersed species experienced only a 47% reduction, and explosively dispersed
      species showed increased seed numbers arriving. The increase in explosively
      dispersed seeds consisted entirely of the seeds of several shrub species, a
      result consistent with greater in situ seed production by explosively dispersed
      shrubs that survived gap formation or recruited immediately thereafter. Lianas
      did relatively better in seed arrival into gaps than did trees, suffering less of
      a reduction in seed arrival compared with understory sites. This result could in
      large part be explained by the greater predominance of wind dispersal among
      lianas: there were no significant differences between lianas and trees when
      controlling for dispersal syndromes. Our results show that seed arrival in gaps
      is very different from seed arrival in the understory in both total seeds
      arriving and functional composition. Differential seed arrival in gaps will help
      to maintain wind-dispersed, explosively dispersed, and possibly other understory
      species in the community of plants that regenerate in gaps.

PMID- 23951716
TI  - Understanding relationships among abundance, extirpation, and climate at
      ecoregional scales.
AB  - Recent research on mountain-dwelling species has illustrated changes in species
      distributional patterns in response to climate change. Abundance of a species
      will likely provide an earlier warning indicator of change than will occupancy,
      yet relationships between abundance and climatic factors have received less
      attention. We tested whether predictors of counts of American pikas (Ochotona
      princeps) during surveys from the Great Basin region in 1994-1999 and 2003-2008
      differed between the two periods. Additionally, we tested whether various modeled
      aspects of ecohydrology better predicted relative density than did average annual
      precipitation, and whether risk of site-wide extirpation predicted subsequent
      population counts of pikas. We observed several patterns of change in pika
      abundance at range edges that likely constitute early warnings of distributional
      shifts. Predictors of pika abundance differed strongly between the survey
      periods, as did pika extirpation patterns previously reported from this region.
      Additionally, maximum snowpack and growing-season precipitation resulted in
      better-supported models than those using average annual precipitation, and
      constituted two of the top three predictors of pika density in the 2000s surveys
      (affecting pikas perhaps via vegetation). Unexpectedly, we found that extirpation
      risk positively predicted subsequent population size. Our results emphasize the
      need to clarify mechanisms underlying biotic responses to recent climate change
      at organism-relevant scales, to inform management and conservation strategies for
      species of concern.

PMID- 23951717
TI  - Persistence of black-tailed prairie-dog populations affected by plague in
      northern Colorado, USA.
AB  - The spatial distribution of prairie dog (Cynomys ludovicianus) colonies in North
      America has changed from large, contiguous populations to small, isolated
      colonies in metapopulations. One factor responsible for this drastic change in
      prairie-dog population structure is plague (caused by the bacterium Yersinia
      pestis). We fit stochastic patch occupancy models to 20 years of prairie-dog
      colony occupancy data from two discrete metapopulations (west and east) in the
      Pawnee National Grassland in Colorado, USA, that differ in connectivity among
      suitable habitat patches. We conducted model selection between two hypothesized
      modes of plague movement: independent of prairie-dog dispersal (colony-area) vs.
      plague movement consistent with prairie-dog dispersal (connectivity to extinct
      colonies). The best model, which fit the data well (area under the curve [AUC]:
      0.94 west area; 0.79 east area), revealed that over time the proportion of extant
      colonies was better explained by colony size than by connectivity to extinct
      (plagued) colonies. The idea that prairie dogs are not likely to be the main
      vector that spreads Y. pestis across the landscape is supported by the
      observation that colony extinctions are primarily caused by plague, prairie-dog
      dispersal is short range, and connectivity to extinct colonies was not selected
      as a factor in the models. We also conducted simulations with the best model to
      examine long-term patterns of colony occupancy and persistence of prairie-dog
      metapopulations. In the case where the metapopulations persist, our model
      predicted that the western metapopulation would have a colony occupancy rate
      approximately 2.5 times higher than that of the eastern metapopulation (-50%
      occupied colonies vs. 20%) in 50 years, but that the western metapopulation has 
      80% chance of extinction in 100 years while the eastern metapopulation has a less
      than 25% chance. Extinction probability of individual colonies depended on the
      frequency with which colonies of the same size class occurred in the
      metapopulation. Thus, the long-term persistence of prairie-dog metapopulations
      depended on specific details of the metapopulation.

PMID- 23951718
TI  - Dependent vs. independent juvenile survival: contrasting drivers of variation and
      the buffering effect of parental care.
AB  - Juvenile survival is often found to be more sensitive than adult survival to
      variation in environmental conditions, and variation in juvenile survival can
      have significant impacts on population growth rates and viability. Therefore,
      understanding the population-level effects of environmental changes requires
      understanding the effects on juvenile survival. We hypothesized that parental
      care will buffer the survival of dependent juveniles from variation in
      environmental conditions, while the survival of independent juveniles will
      respond more strongly to environmental variation and, in turn, drive the overall
      variation in annual juvenile survival. We tested this parental-care hypothesis
      using a 30-year mark-recapture data set to model the survival of juvenile Song
      Sparrows (Melospiza melodia) during the dependent and independent stages. We
      examined the effects of weather, density, and cohort mean fledge date and body
      mass on annual variation in survival during the first 12 weeks after fledging, as
      well as effects of individual fledge date and body mass on individual variation
      in survival. The primary driver of annual variation in juvenile survival was
      precipitation during the previous rainy season, consistent with an effect on food
      availability, which had a strong positive effect on the survival of independent
      juveniles, but no effect on dependent juveniles. We also found strong support for
      effects of body mass and fledge date on individual survival probability,
      including striking differences in the effect of fledge date by stage. Our results
      provided evidence that different mechanisms influence juvenile survival during
      each stage of fledgling development, and that parental care buffers the survival
      of dependent juveniles from variation in environmental conditions. Consequently,
      variation in juvenile survival was driven by independent juveniles, not dependent
      juveniles, and studies focused only on survival during the dependent stage may
      not be able to detect the major drivers of variation in juvenile survival. We
      recommend that future efforts to understand or project the population-level
      effects of environmental change not only examine the effects on juvenile
      survival, but specifically consider the survival of independent juveniles, as
      well as how the drivers of variation in juvenile survival may vary by stage.

PMID- 23951719
TI  - Leaf litter quality induces morphological and developmental changes in larval
      amphibians.
AB  - Aquatic consumers exhibit many types of inducible phenotypic responses to
      variation in resource quantity and quality. Leaf litter constitutes a primary
      resource in freshwater systems, and variation in litter quality can alter the
      growth and development of aquatic consumers. It is therefore reasonable to
      hypothesize that variation in litter quality might also induce phenotypic changes
      in consumers. To test this hypothesis, we exposed two densities of wood frog
      (Lithobates sylvaticus [Rana sylvatica]) tadpoles to six chemically distinct
      species of leaf litter from temperate broadleaf and coniferous trees. After
      several weeks, we quantified development rate, growth rate, intestinal length,
      size of the oral disc, and five external dimensions of the tadpoles. In addition
      to substantial changes in growth and development rates, we found striking changes
      in all morphological responses among different leaf litter environments,
      including up to 14% longer intestines, 11% deeper tails, and 6% deeper tail
      muscles. In addition, we found strong relationships of total nitrogen content
      with all morphological features except growth rate. Our results indicate that
      differences in resource quality can induce phenotypic changes that are as large
      as or larger than changes induced by resource quantity. Our study also has
      substantial implications for the future of aquatic consumers living in forested
      wetlands given that these forests are currently experiencing widespread changes
      in tree composition.

PMID- 23951720
TI  - Benthic algae stimulate leaf litter decomposition in detritus-based headwater
      streams: a case of aquatic priming effect?
AB  - In detritus-based ecosystems, autochthonous primary production contributes very
      little to the detritus pool. Yet primary producers may still influence the
      functioning of these ecosystems through complex interactions with decomposers and
      detritivores. Recent studies have suggested that, in aquatic systems, small
      amounts of labile carbon (C) (e.g., producer exudates), could increase the
      mineralization of more recalcitrant organic-matter pools (e.g., leaf litter).
      This process, called priming effect, should be exacerbated under low-nutrient
      conditions and may alter the nature of interactions among microbial groups, from
      competition under low-nutrient conditions to indirect mutualism under high
      nutrient conditions. Theoretical models further predict that primary producers
      may be competitively excluded when allochthonous C sources enter an ecosystem. In
      this study, the effects of a benthic diatom on aquatic hyphomycetes, bacteria,
      and leaf litter decomposition were investigated under two nutrient levels in a
      factorial microcosm experiment simulating detritus-based, headwater stream
      ecosystems. Contrary to theoretical expectations, diatoms and decomposers were
      able to coexist under both nutrient conditions. Under low-nutrient conditions,
      diatoms increased leaf litter decomposition rate by 20% compared to treatments
      where they were absent. No effect was observed under high-nutrient conditions.
      The increase in leaf litter mineralization rate induced a positive feedback on
      diatom densities. We attribute these results to the priming effect of labile C
      exudates from primary producers. The presence of diatoms in combination with
      fungal decomposers also promoted decomposer diversity and, under low-nutrient
      conditions, led to a significant decrease in leaf litter C:P ratio that could
      improve secondary production. Results from our microcosm experiment suggest new
      mechanisms by which primary producers may influence organic matter dynamics even
      in ecosystems where autochthonous primary production is low.

PMID- 23951721
TI  - The relative importance of exogenous and substrate-derived nitrogen for microbial
      growth during leaf decomposition.
AB  - Heterotrophic microbes colonizing detritus obtain nitrogen (N) for growth by
      assimilating N from their substrate or immobilizing exogenous inorganic N.
      Microbial use of these two pools has different implications for N cycling and
      organic matter decomposition in the face of the global increase in biologically
      available N. We used sugar maple leaves labeled with 15N to differentiate between
      microbial N that had been assimilated from the leaf substrate (enriched with 15N)
      or immobilized from the water (natural abundance 15N:14N) in five Appalachian
      streams ranging in ambient NO3(-)N concentrations from about 5 to 900 microg NO3(
      )N/L. Ambient NO3(-) concentration increased sugar maple decomposition rate but
      did not influence the proportion of microbial N derived from substrate or
      exogenous pools. Instead, these proportions were strongly influenced by the
      percentage of detrital ash-free dry mass (AFDM) remaining. Substrate-derived N
      made up a large proportion of the microbial N after the first 24 h in all
      streams. Detrital and microbial isotopic 15N signatures approached that of the
      water as decomposition progressed in all streams, suggesting that exogenous N may
      be the predominant source of N for meeting microbial requirements even when
      exogenous N concentrations are low. Our results support predictions of more rapid
      decomposition of organic matter in response to increased N availability and
      highlight the tight coupling of processes driving microbial N cycling and organic
      matter decomposition.

PMID- 23951722
TI  - Functional traits explain phytoplankton responses to environmental gradients
      across lakes of the United States.
AB  - Ecological communities exhibit regular shifts in structure along environmental
      gradients, but it has proved difficult to dissect the mechanisms by which
      environmental conditions determine the relative success of species. Functional
      traits may provide a link between environmental drivers and mechanisms of
      community membership, but this has not been well tested for phytoplankton, which
      dominate primary production in many aquatic ecosystems. Here we test whether
      functional traits of phytoplankton can explain how species respond to gradients
      of light and phosphorus across U.S. lakes. We find that traits related to light
      utilization and maximum growth rate can predict species' differential responses
      to the relative availability of these resources. These results show that
      laboratory-measured traits are predictive of species' performance under natural
      conditions, that functional traits provide a mechanistic foundation for community
      ecology, and that variation in community structure is predictable in spite of the
      complexity of ecological communities.

PMID- 23951723
TI  - Interactions between sea urchin grazing and prey diversity on temperate rocky
      reef communities.
AB  - While we frequently observe that increasing species richness within a trophic
      level can increase the rates of predation or herbivory on lower trophic levels,
      the general impacts of prey diversity on consumption rates by their predators or
      herbivores remains unclear. Here we report the results of two field experiments
      that examined how subcanopy sessile species richness affects rates of consumption
      by sea urchins. We crossed a natural gradient of species richness in a benthic
      subtidal community of understory macroalgae and sessile invertebrates against two
      experimental gradients of urchin density (0-50 and 0-14 individuals) in 0.5-m2
      fenced plots. We found that the percent cover of macroalgae and invertebrates
      consumed by urchins was greater at higher levels of sessile prey species
      richness. However, this positive association between prey richness and sea urchin
      consumption was only apparent at low urchin densities; at high urchin densities
      nearly all algal and invertebrate biomass was consumed irrespective of sessile
      species richness. The positive relationship between prey richness and urchin
      consumption was also stronger when the abundance of prey species was more even
      (i.e., higher Simpson's evenness). Collectively, our results show that the
      consumptive impacts of urchins on kelp forest understory communities increases as
      a function of species diversity (both prey richness and evenness), but that prey
      diversity becomes irrelevant when urchins reach high densities.

PMID- 23951724
TI  - Feedbacks underlie the resilience of salt marshes and rapid reversal of consumer
      driven die-off.
AB  - Understanding ecosystem resilience to human impacts is critical for conservation
      and restoration. The large-scale die-off of New England salt marshes was
      triggered by overfishing and resulted from decades of runaway crab grazing. In
      2009, however, cordgrass began to recover, decreasing die-off -40% by 2010. We
      used surveys and experiments to test whether plant-substrate feedbacks underlie
      marsh resilience. Initially, grazer-generated die-off swept through the
      cordgrass, creating exposed, stressful peat banks that inhibited plant growth.
      This desertification cycle broke when banks eroded and peat transitioned into mud
      with fewer herbivores, less grazing, and lower physical stress. Cordgrass
      reestablished in these areas through a feedback where it engineered a recovery
      zone by further ameliorating physical stresses and facilitating additional
      revegetation. Our results reveal that feedbacks can play a critical role in
      rapid, reversible ecosystem shifts associated with human impacts, and that the
      interplay of facilitative and consumer interactions should be incorporated into
      resilience theory.

PMID- 23951725
TI  - [Usefulness of moxifloxacin tablet on nursing and health care-associated
      pneumonia--a prospective study with a simple suspension method].
AB  - Patients with nursing and health care-associated pneumonia (NHCAP) include those
      at risk for aspiration or those who have difficulties to take pills. We conducted
      a prospective study to examine the efficacy and safety of moxifloxacin (MFLX)
      administration through an enteral feeding tube by a simple suspension method in
      patients with NHCAP receiving long-term care at the hospital. The study was
      performed in subjects meeting the definition of NHCAP according to the Japanese
      Respiratory Society amongst patients with pneumonia who were fed by a feeding
      tube under long-term care at Makita General Hospital during the period from Dec.
      2010 to Oct. 2011. A dose of 400 mg MFLX was administered once daily for three
      consecutive days, as a rule, through a gastrostomy or nasogastric feeding tube by
      a simple suspension method. The primary endpoint was a test of cure (TOC) 7 days
      after the last administration. Sixteen patients were included in the analysis of
      the study. As the patient background, 11 were assessed as long-term care level 5,
      5 were not receiving care, and the Eastern Cooperative Oncology Group Performance
      Status (ECOG-PS) score was 4 in all patients. Twelve (75%) had experience of
      aspiration while 4 (25%) had none, and all had some underlying diseases
      (complications). The severity of pneumonia according to the A-DROP scoring system
      was mild in 1 patient (6%), moderate in 14 patients (88%) and severe in 1 patient
      (6%). A test of cure 7 days after the last administration, which was the primary
      endpoint, showed an efficacy rate of 81.3% (13/16 patients), while the efficacy
      evaluation 3 days after administration, which was an endpoint for early phase
      drug efficacy, showed that the drug was effective in all patients (100%; 16/16
      patients). Neither adverse drug reactions nor abnormal laboratory findings were
      observed. MFLX administration through an enteral feeding tube by a simple
      suspension method was shown to be as highly effective as injection in patients
      with NHCAP having eating and swallowing disorders, indicating its potential to
      become an alternative option to conventional intravenous injection therapy.

PMID- 23951726
TI  - Evaluation of antibacterial activities of flomoxef against ESBL producing
      Enterobacteriaceae analyzed by Monte Carlo simulation.
AB  - The growing number of infection caused by extended-spectrum beta-lactamase (ESBL)
      producing pathogens has prompted a more rational use of available antibiotics
      because of the paucity of new, effective agents. Flomoxef (FMOX) is one of the
      beta-lactam antibiotic which is stable against beta-lactamase. In this study, the
      antibacterial activity of FMOX was investigated, and Monte Carlo Simulation was
      conducted to determine the appropriate dosing regimens of FMOX based on the
      probability of target attainment (TA%) at the critical drug exposure metric of
      time that drug concentrations remain above 40% (showing bacteriostatic effect) or
      70% (showing bactericidal effect) of time during which plasma concentration above
      minimum inhibitory concentration (MIC) of the drug (T(>MIC)) against the ESBL
      producing Enterobacteriaceae. The effective regimens to achieve 80% of TA% at 70%
      of T(>MIC) were 1 g every 8 hours with 2-4 hours infusion, and 1 g every 6 hours
      with 1-4 hours infusion. Moreover, all the tested regimens were effective to
      achieve 80% of TA% at 40% of T(>MIC). These results of pharmacokinetics/
      pharmacodynamics (PK/PD) modeling showed the potential efficacy of FMOX against
      bacterial infections caused by ESBL producing Enterobacteriaceae.

PMID- 23951727
TI  - Is Clostridium difficile infection influenced by antimicrobial use density in
      wards?
AB  - This study was performed to elucidate the relationship between antimicrobial use
      density (AUD) and Clostridium difficile infection (CDI) manifesting as
      antimicrobial-associated diarrhea (AAD) in hospital wards during a 4-year period.
      Case definition of CDI was an adult exhibiting AAD with a daily stool frequency
      of three or more, arising at least 48 hours after ward admission, and fecal
      samples testing positive for toxin (A and/or B). Metronidazole or vancomycin was
      orally administered as treatment. AUDs were calculated for a total of 21
      antimicrobials in a span of 48 months and nine wards. We included the average
      value of AUDs, representing two succeeding months of sample submission into the
      sample information. We also entered data on the 2-year division and intensified
      contact precaution for statistical analysis. Of a total of 463 cases, 95 (20.5%)
      were CDI-positive. Multivariate regression analysis showed odds ratios [OR] of
      1.739 (95% confidence interval [CI] of 1.050 - 2.881, P = 0.032) and 1.598 (95%
      CI of 1.006 -2.539, P = 0.047) for clindamycin and piperacillin, respectively in
      AUD. Thus increased ward AUDs of clindamycin and piperacillin may run the risk of
      CDI.

PMID- 23951728
TI  - [Safety and pharmacokinetics of 400 and 600 mg arbekacin sulfate to healthy male
      volunteers].
AB  - We assessed the safety and pharmacokinetics of arbekacin sulfate (ABK, brand
      name: Habekacin injection) in single and 7-day multiple administration of ABK 400
      and 600 mg as potency to healthy male volunteers. In the single administration of
      ABK 400 and 600 mg (over 30 min, drip infusion), C(max) values were 41.0 +/- 3.6
      microg/mL and 63.0 +/- 9.9 microg/mL, respectively. Serum ABK concentrations at
      60 min (C(peak)) after the start of administration were 23.2 +/- 2.9 microg/mL
      and 38.5 +/- 3.3 microg/mL, respectively, and the mean serum ABK concentrations
      at 24 hr (C(trough)) after the start of administration were less than 0.4
      microg/mL (LOQ: limited of quantitation). C(max), Cpeak and AUC(0-infinity) were
      increased with doses, and t1/2, CL(tot), CL(r) V(ss) and urinary excretion were
      comparable at both doses. In the multiple administration of ABK 400 and 600 mg
      (over 30 min, drip infusion) once a day for 7 days, C(max0, C(peak) and AUC(0
      infinity) were comparable from the 1st day through to 7th day and increased with
      doses. After the administration, the serum ABK concentrations were decreased with
      time, and the means of C(trough) were 0.4 microg/mL (LOQ) -0.5 microg/mL, which
      showed ABK has no tendency toward accumulation. In addition, t1/2, CL(tot), CL(r)
      V(ss) and urinary excretion were constant throughout administration days at
      either dose, and CL(tot) containing CL(r) was not decreased. There were no
      notable changes in the functions of the kidney, auditory organs, etc. Based on
      the above-mentioned results, when ABK 400 or 600 mg was intravenously
      administered over 30 min once or once a day for 7 days to the healthy male
      volunteers with normal renal clearance, it is suggested there were no problems in
      terms of safety, and C(max) were 36.7-54.1 and 44.2-78.5 microg/mL, respectively.
      In addition, C(trough) was 0.5 microg/mL or lower at either doses and ABK was not
      accumulated in multiple administration of ABK. ABK was, therefore, expected to
      have good safety profile and favorable pharmacokinetics.

PMID- 23951729
TI  - [Community psychiatry today].

PMID- 23951730
TI  - [The future of psychiatry in 17 points].

PMID- 23951731
TI  - [A 3rd long-term autism plan (2013 - 2017)].

PMID- 23951732
TI  - [Nitroprusside treatment of schizophrenic patients].

PMID- 23951733
TI  - [A digital platform for caregivers].

PMID- 23951734
TI  - [Addictions without substances, an unrecognized pathology].

PMID- 23951735
TI  - [Georges Devereux on the big screen].

PMID- 23951737
TI  - [The challenges and perspectives of collaborative networking].
AB  - The mental health action plan for Europe dates back to 2005 and sets out the
      terms for drawing up, implementing and strengthening global mental health
      policies in all European countries. While in the area of psychiatry, the
      advantages of working in a network must be emphasised, it can be developed on the
      level of the local community, the health care territory or the department as well
      as on a regional basis.

PMID- 23951736
TI  - [The health care team in psychiatry].

PMID- 23951738
TI  - [The local mental health council, a concrete tool for networking].
AB  - Mental health needs are expressed well beyond the doors of the psychiatric
      hospital. The health and social sectors are also confronted with situations of
      psychological suffering. The local mental health council offers solutions to
      professionals faced with this issue. The creation of the local mental health
      council and the collaborative way of working which it promotes give rise to
      projects aimed at improving mental health care.

PMID- 23951739
TI  - [Opening up psychiatric care].
AB  - The post-war phase of the deinstitutionalisation of psychiatry, which led to the
      legal recognition of the sector, has been followed by the years of economic
      crisis. As in the past, such times favour the exclusion of the weakest. As
      resources dwindle, only the clinical meaning, the dynamism and creativity of the
      nursing teams can ensure the emergence of new solutions for complex care
      situations.

PMID- 23951740
TI  - [The Mobile Precarity Team: a tool for building relations].
AB  - The Mobile Precarity Team is based in the medical-psychological centre. It works
      with people in situations of exclusion, in collaboration with social workers,
      doctors, hospitals, emergency housing centres and social action associations and
      charities. The main objective is to encourage people to seek medical care.

PMID- 23951741
TI  - [The network, a framework for a structured partnership].
AB  - A regional mental health care network in Yvelines organises and coordinates
      pooled resources in order to improve prevention, care and the integration of
      people in the area of mental health. The partner organisations which make up the
      network are from the social and medical-social sectors. The role of the network
      with the departmental centre for disabled people has been particularly successful
      in working to reintegrate patients.

PMID- 23951742
TI  - [Bibliography].

PMID- 23951743
TI  - [Nursing care wall planning].
AB  - Nursing care wall planners are not a tool for assessing workload, but a means of
      providing coherence and individualised monitoring of care. Its application is
      focused not only on team organisation, but also on the patient's needs.

PMID- 23951745
TI  - [Frantz Fanon].

PMID- 23951746
TI  - Congressional biodiversity.

PMID- 23951744
TI  - [Outpatient withdrawal programme: advanced practice in addictology].
AB  - Advanced nursing practices are procedures enabling nurses to carry out, in a
      structured and predefined manner, tasks usually entrusted to doctors. Introduced
      in France by the Berland reports of 2003 and 2006, advanced nursing practices
      remain under-developed in the fields of psychiatry and addictology. In this
      context, Lille regional and university hospital has set up an outpatient
      programme for alcohol withdrawal, a scheme coordinated by a nurse, authorised to
      modifythe treatment dosage according to the patient's clinical state and who is
      supported by a network of caregivers during the period of medicalised withdrawal.

PMID- 23951747
TI  - A position statement from the Academy of Prosthodontists of South Africa.

PMID- 23951749
TI  - Oral medicine case book 43--focal epithelial hyperplasia in an HIV-seropositive
      child.

PMID- 23951748
TI  - Oligodontia--treatment planning of a case.

PMID- 23951750
TI  - Oral medicine case book 44--lip carcinoma.

PMID- 23951751
TI  - General practitioner's radiology case 106. Ectodermal dysplasias.

PMID- 23951752
TI  - Practice management.

PMID- 23951753
TI  - Dental ethics case 26. The incompetent geriatric patient.

PMID- 23951754
TI  - A focus on shared responsibility in the management of periodontal and systemic
      diseases.

PMID- 23951755
TI  - The association between periodontitis and systemic health: an overview.
AB  - A putative association between periodontitis and several systemic conditions is
      reflected in the literature. However, the nature of the relationship is not fully
      understood and at times may be confusing. It is reported that active
      periodontitis may contribute towards the development of a high systemic disease
      burden and that oral heath maintenance, following effective periodontal
      treatment, will improve the quality of life of the patient and reduce the
      morbidity of these systemic conditions. Evidence has been presented of direct
      relationships between periodontal disease and cardiovascular disease, with pre
      term low-birth-weight infants and with diabetes mellitus, amongst others. Whether
      these relationships are causal or not, still needs to be established by further
      investigation. In the endeavour to make sense of this rapidly advancing area of
      research, a series of papers is planned for publication during the year 2012.
      These evidence-based, condensed reviews will hopefully provide clarity on the
      associations and/or possible causal relationships of periodonttis with specific
      systemic conditions. The present paper introduces and reviews the concept of the
      inter-relationships between periodontal and systemic health. The importance of a
      multidisciplinary approach with co-operation between dental and medical
      professionals, whether general practitioners or specialists, in the management of
      patients with these diseases is highlighted.

PMID- 23951756
TI  - Factors influencing the life span of modern root canal instruments--a literature
      review.

PMID- 23951758
TI  - Maxillo-facial radiology case 107. Carcinoma.

PMID- 23951757
TI  - Hard palate cleft and oro-nasal fistula reconstruction utilising a resorbable
      sheet.

PMID- 23951759
TI  - Oral medicine case book 46: squamous cell carcinoma of the tongue.

PMID- 23951760
TI  - Ethics corner: patient's access to records.

PMID- 23951761
TI  - Informed consent... a conflict of interest?

PMID- 23951762
TI  - Carpe diem.

PMID- 23951763
TI  - SADA communique: Managed care and preferred provider contracts.

PMID- 23951764
TI  - Anti-smoking campaigns.

PMID- 23951765
TI  - Periodontitis and cardiovascular disease.
AB  - Periodontal medicine has been studied and reviewed extensively since its
      introduction to the dental fraternity. The association of periodontal disease
      with and its effects on the cardiovascular system are amongst the many topics
      explored. A summary of the research into these associations and the possible
      mechanisms of any relationship is presented. Although a link between these two
      chronic inflammatory diseases is evident, the very heterogeneity of the relevant
      studies has not provided evidence sufficient to support an actual causal
      relationship. More stringent epidemiologic and intervention studies are required.

PMID- 23951766
TI  - In vitro comparison of the compressive strengths of seven different provisional
      crown materials.

PMID- 23951767
TI  - Awareness and knowledge of prophylaxis for infective endocarditis in patients
      with severe rheumatic heart disease.
AB  - Prevention of infective endocardit s (IE) is mportant because it has a high
      mortalty rate.This study sets out to to gather information from patients who were
      at risk of developing IE of their knowledge of the need for prophylaxis for the
      disease. Forty-one black patients suffering from severe rheumatic heart disease
      (RHD) were interviewed. Only one patient (2.4%) was regularly visiting a dentist
      to maintain good oral health and only five (12.2%) had received advice about the
      need for antibiotic cover prior to dental extraction. The vast majority of
      patients (97.5%) visited a dentist only when driven by dental pain, 36.6 % had to
      travel for more than an hour to reach their nearest dentist, and 87.8% indicated
      that they brushed their teeth. It may be concluded that in this group of black
      patients with severe RHD there was a lack of knowledge of the need for and of
      measures recommended for prophylaxs against IE. In addition, attempts by the
      health care team to ensure good oral health and access to dental care for these
      patients were inadequate, if not non-existent.

PMID- 23951768
TI  - Safe use of X-rays by dentists.

PMID- 23951769
TI  - Maxillo-facial radiology case 108. Ewing's sarcoma.

PMID- 23951770
TI  - Oral Medicine Case Book 47: Oral neurofibroma.

PMID- 23951771
TI  - Ethics corner. Periodontal treatment & allegations of neglect.

PMID- 23951772
TI  - Perspective - an essential attribute.

PMID- 23951773
TI  - Ethics for sale.

PMID- 23951774
TI  - A comparative study of three imaging modalities currently used in the assessment
      of patients for maxillofacial surgery.
AB  - Diagnostic imaging is pivotal in clinical maxillofacial evaluation. This study
      evaluated and compared the use of conventional radiographs (CR) with two
      dimensional (2D) and three-dimensional (3D) computed tomography (CT) in patients
      requiring maxillofacial surgery. Pre-surgical records of sixty five patients who
      had undergone routine CR, 2D CT and 3D CT were selected and classified into the
      categories of traumatic injury, pathology and deformities. The accuracy of image
      analysis, diagnosis and treatment planning were scored and the data statistically
      analysed. 2D CT scanning was more effective diagnostically and is preferred for
      cases of traumatic injury (44%, SD=0.54, p>0.05) and pathology (34%, SD=0.47,
      p>0.05) whilst 3D CT imaging was indicated for the deformity category (22%,
      SD=0.58, p>0.05). Linear comparisons between radiographic modalities within each
      clinical group revealed significant differences (p<0.05). Multiplanar reformatted
      (MPR) 2D cross sectional CT views offered additional imaging information.
      CONCLUSION: 2D CT scanning is an excellent imaging modality for the majority of
      craniomaxillofacial surgical cases. 3D CT scanning is also recommended for cases
      of trauma and pathology. Both 2D CT and 3D CT scanning are vital in
      craniomaxillofacial deformities and reconstructive surgery.

PMID- 23951775
TI  - Use of the passive lower lingual arch in the management of anterior mandibular
      crowding in the mixed dentition.
AB  - Leeway space preservation in the mixed dentition is a well-documented method of
      space management. In the mandibular arch it may be saved for utilisation in the
      correction of minor anterior crowding by the placement of a passive lower lingual
      arch (LLA) during the transition from the mixed dentition to the permanent
      dentition.

PMID- 23951776
TI  - Guidelines for the selection of tooth whitening products amongst those available
      on the market.
AB  - BACKGROUND: Several tooth whiteners are available on the market, and the ideal
      choice should be determined by efficacy and optimal clinical results. OBJECTIVES:
      The purpose of this study was to compare the reported clinical success rates of
      different tooth whitening products. SEARCH STRATEGY: The relevant literature
      (1998 - 2011) was studied, using as sources the databases: Google Scholar,
      Science Direct, Medline and Pubmed. SELECTION CRITERIA: The material was clearly
      identified, the manufacturers' instructions were respected and the sample size
      stated. RESULTS AND CONCLUSIONS: This descriptive report on 49 papers focuses on
      the total colour change, measured with a calibrated shade guide and also
      numerically (colourimeter, chromameter or spectrophotometer), the relapse of the
      colour change and tooth sensitivity. In general, the dentist-supervised at-home
      bleaching and the in-office treatment gave approximately the same initial
      percentage improvement of tooth whitening. However, the relapse after a four week
      or longer period was significantly higher for the in-office treatment. The
      treatment of choice should be a dentist supervised at-home bleaching product
      which generally contains approximately 10% carbamide peroxide applied over about
      14 days for about eight hours per night. Tooth sensitivity should not be a
      general problem although some subjects might choose to discontinue treatment as a
      result of sensitivity.

PMID- 23951777
TI  - Maxillo-facial radiology case 109. Benign osteoblastoma.

PMID- 23951778
TI  - Oral Medicine Case Book 48: epidermolysis bullosa.

PMID- 23951779
TI  - Practitioners enrolling their patients in clinical research.

PMID- 23951780
TI  - Message from the deputy vice chancellor.

PMID- 23951781
TI  - The history of the School of Oral Health Sciences ... a summarised version.

PMID- 23951783
TI  - Caries prevalence among HIV-infected children between four and ten years old at a
      paediatric virology out-patients ward in Johannesburg, Gauteng Province, South
      Africa.
AB  - INTRODUCTION: There remains controversy in the literature as to whether children
      with HIV are at greater risk for caries than healthy children. OBJECTIVES: To
      determine the caries prevalence and unmet treatment needs (UTN) in a cohort of
      HIV+ive children between the ages of four and ten years who were attending the
      Charlotte Maxeke Paediatric Virology out-patients ward and to compare the results
      with the data of the National Children's Oral Health Survey (NCOHS). METHODS:
      This descriptive, analytic study comprised of a sample of 277 children attending
      the Paediatric Virology out patients ward at the Charlotte Maxeke Hospital over a
      one year period. The caries status was measured using WHO guidelines and
      criteria. RESULTS: Among the 93 children aged between four and five years, the
      caries prevalence of the primary dentition was 70.9%; the dmft was 5.1 and the
      UTN was 99.6%. In the 62 six year olds and 122 seven to ten year olds, the caries
      prevalence in the primary teeth was 62.9% and 67.2%; the dmft was 4.2 and 4 and
      the UTN 100% and 87.8% respectively. The mean dmft of the four, five and six year
      olds was significantly higher than those reported in the NCOHS. The four, five
      and sx-year old HIV positive children had a 1.4 times higher risk of caries
      development than children from the general population (p < 0.002). CONCLUSION:
      This cohort of HIV-infected children had significantly higher caries prevalence,
      dmft and UTN than did children from the general population.

PMID- 23951782
TI  - Dental caries prevalence in children attending special needs schools in
      Johannesburg, Gauteng Province, South Africa.
AB  - INTRODUCTION: Anecdotal evidence from clinical data in Johannesburg suggests that
      there is a high burden of dental caries among children with special health care
      needs (CSHCN) in Johannesburg. OBJECTIVES: To determine the prevalence of dental
      caries and Unmet Treatment Needs in children with cerebral palsy, hearing,
      learning and mental disabilities attending special needs schools in Johannesburg
      and to compare these with data from the National Children's Oral Health Survey
      (NCOHS) METHODS: This cross-sectional analytical study comprised of 882 children
      attending five special needs schools in Johannesburg. Stratified randomised
      sampling of the participating schools was done and the schools were stratified by
      disability. Caries status was recorded via the dmft/DMFT index using WHO criteria
      and guidelines. RESULTS: The mean age of the participants was 10.5 years; with a
      caries prevalence of 27.55% and 33.56% in the primary and permanent dentition
      respectively. The highest unmet treatment need of 100% was found in the permanent
      dentition of the hearing impaired group followed by 90.77% in the primary
      dentition of the cerebral palsy group. In general no significant difference was
      found when the dmft/DMFT for CSHCN and NCOHS were compared except in the hearing
      impaired age groups four to five and six (both primary dentition) where
      significantly higher dmft scores (3.58 vs. 2.4; 3.85 vs. 2.9; p < 0.05) were
      found. CONCLUSION: Children with special health care needs had lower caries
      prevalence compared with the general population and higher unmet treatment needs
      regardless of the type of disability.

PMID- 23951784
TI  - Caries status among children in the West Rand District of Gauteng Province, South
      Africa.
AB  - INTRODUCTION: There is a lack of data about the prevalence and clinical
      consequences of dental caries in the West Rand. However dental caries does appear
      to be a substantial public health problem in Gauteng. OBJECTIVE: This study set
      out to determine the prevalence and clinical consequences of dental caries among
      school children in the West Rand district of Gauteng. METHODOLOGY: This was a
      cross-sectional study comprised of 800 pre-school and primary school children six
      to eight years old. Cluster sampling was used to select the participating
      schools. The oral health status was determined by using the DMFT/dmft and
      PUFA/pufa indices. RESULTS: Of the 800 children, 282 were in the four to five
      year old age group and 518 were six to eight years old. For four to five year
      olds the mean dmft score was 2.24 and the prevalence of caries 49%. The clinical
      consequence of caries was scored with a mean pufa index of 2.9 and the percentage
      of untreated decay was 47%. For six to eight year olds the mean DMFT/dmft scores
      were 0.1 and 2.4 respectively and the prevalence of caries 46%. The clinical
      consequence of caries scored with the PUFA/pufa index was 0.0 and 3.4
      respectively and the percentage of untreated decay was 44%. CONCLUSION: There are
      high levels of untreated caries in children in this district. The pufa scores
      ndicate that children suffer serious consequences of untreated decay.

PMID- 23951785
TI  - A comparison of endodontic treatment outcomes between HIV-positive and HIV
      negative patients.
AB  - INTRODUCTION: There has been some surmise that immunocompromised patients may not
      be candidates for endodon tic therapy. AIM: To compare the clinical presentation,
      treatment, and treatment outcomes of HIV+ve and HIV-ve patients receiving
      endodontic therapy. METHOD: Fifty-nine HIV-ve and 46 HIV+ve patients who
      consented to join the study were sequentially selected from those presenting at
      the hospital. Clinical features were recorded for pain on palpation and
      percussion, thermal sensitivity, radiographic appearance, swelling, and time for
      treatment. Endodontic outcomes were assessed at 6, 12, 18 and 24 months. RESULTS:
      There was no statistically significant difference in the presenting signs and
      symptoms of the two groups, although HIV+ve patients reported more severe pain.
      HIV+ve patients presented with mainly anterior teeth requiring therapy, but only
      three teeth (24%) had caries. Active caries was present in 71% (42) of the HIV-ve
      patients and in only 7% (three) of the HIV +ve patients. Treatment time for
      comparable teeth in the HIV-ve patients (52 minutes) was nearly half that of the
      HIV+ve (112 minutes) patients, mainly due to the latter experiencing excessive
      canal bleeding during treatment. There was no significant difference in the final
      outcome at 24 months, though resolution of signs and symptoms tended to occur
      earlier in the HIV-ve patients. CONCLUSIONS: Endodontic therapy is not contra
      indicated HIV+ve patients, although treatment times may be longer, and time to
      full resolution may take longer in some of these patients. A comparison of
      endodontic treatment outcomes between HIV positive and HIV negative patients.

PMID- 23951786
TI  - Clade-related phenotypic switching among fluconazole resistant Candida albicans
      isolates.
AB  - INTRODUCTION: C. albicans undergoes phenotypic switchng, a putative virulence
      trait assisting the organism to adapt to different environments. Although this
      switching has been studied among C. albicans isolates, not much is known about
      the process among various C. albicans clades (a group of genetic variants within
      a single species). AIM: To determine whether phenotypic switching among
      fluconazole resistant C. albicans isolates is clade-related. METHODS: Fifteen
      fluconazole resistant C. albicans isolates from different clades were studied.
      Phenotypic switching was determined by a method previously described. Switching
      behaviour and different colony morphologies among different clades were compared.
      RESULTS: Phenotypic switching was observed in all clades, with clade SA
      exhibiting the most switching (75%), and clade NG the east (5.6%). Stipple was
      the most dominant phenotype observed in all clades (p = 0.024), occurring mostly
      in clade SA (35%). Irregular wrinkle phenotype was dominant in clade SA (62%).
      CONCLUSION: Phenotypic switching was clade-related. Highest switching in clade SA
      isolates suggests better survival un der adverse conditions. Stipple and
      irregular wrinkle phenotypes among clade SA isolates need to be studied further.

PMID- 23951787
TI  - Failure rate of high-viscosity GIC based ART compared with that of conventional
      amalgam restorations--evidence from an update of a systematic review.
AB  - INTRODUCTION: Atraumatic Restorative Treatment (ART) involves using only hand
      instruments for removing carious tooth tissue and then restoring the resulting
      cavity with an adhesive restorative material. OBJECTIVE: To answer the question
      as to whether, in patients with carious cavities of any class in primary and
      permanent teeth, ART restorations with high-viscosity glass-ionomer cement (GIC)
      have a higher failure rate than amalgam restorations placed after drilling, in
      tooth cavities of the same size, dentition and follow-up period. METHODS:
      Thirteen databases were searched for relevant trials up to January 2012. Hand
      searching was performed for non indexed journals. References of included trials
      were checked. Prospective, clinical controlled trials with a followup period of
      at least one year were selected. The investi gated outcome was restoration
      failure. Meta-analysis was conducted and internal trial validity was assessed in
      depth. RESULTS: Twenty trials were accepted for review. The majority of the
      results show no differences between the types of intervention. The current
      evidence indicates that the failure rate of high-viscosity GIG/ART restorations
      is not higher than, but is similar to that of conventional amalgam fillings after
      periods longer than six years. There is a risk that these results are affected by
      bias and confirmation by further trials is recommended.

PMID- 23951788
TI  - Tooth colour change with Ozicure Oxygen Activator: a comparative in vitro tooth
      bleaching study.
AB  - INTRODUCTION: This in vitro study compared a new tooth bleaching product, Ozicure
      Oxygen Activator (O3, RSA) with Opalescence Quick (Ultradent, USA) using a
      randomised block design to assess tooth colour change. AIM: Colour change,
      stability and relapse in canine, incisor and premolar teeth was assessed
      following three bleach treatments and subsequent tooth colour assessment.
      METHODS: Ninety nine teeth (canines, incisors and premolars), which were caries
      free, had no surface defects and were within the colour range 1M2 and 5M3 were
      selected. Teeth were randomly divided into the three experimental groups:
      Opalescence Quick, Ozicure Oxygen Activator and control. The three experimental
      groups received three treatments of one hour each over three consecutive days.
      Tooth colour was assessed using the Vitapan 3D Master Tooth Guide (VITA,
      Germany). A General Linear Models test for analysis of variance for a fractional
      design with significance set at P < 0.05 was used to test for significance.
      RESULTS: Both bleaching methods significantly lightened the teeth (P < 0.0001).
      Tooth colour change was mainly after the first hour of tooth bleaching. The tooth
      type was significant in tooth colour change (P = 0.0416). Tooth colour relapse
      and resistance to colour change were observed. CONCLUSIONS: Ozicure Oxygen
      Activator bleached teeth in a manner and to an extent similar to Opalescence
      Quick.

PMID- 23951789
TI  - Assessment and pedagogy: a case study of two oral hygiene lecturers in South
      Africa.
AB  - There is evidence that most South African oral hygiene lecturers lack appropriate
      qualifications in the field of education. Their teaching skills are based mainly
      on clinical and practical experience, and this may impact on their understanding
      of the educational foundations of teaching, learning and assessment. AIM: To
      explore oral hygiene lecturers' knowledge and use of pedagogy and assessment and
      its alignment. METHODS: A qualitative descriptive study design was used and case
      studies of two oral hygiene lecturers, each with qualifications in Education,
      were analyzed according to three themes: curriculum, pedagogy and assessment.
      RESULTS: The results showed that both participants had a good understanding of
      formative assessment (FA) and summative assessment (SA). They made use of FA but
      in neither case was the application ideal. Both used a range of teaching and
      assessment strategies but felt accountable to external demands of meeting
      outcomes. They linked their understanding of pedagogy and assessment to assist in
      the development of their courses and reported that this alignment had improved
      the quality of their programmes. CONCLUSION: This alignment by oral hygiene
      lecturers can influence curricular and pedagogic strategies. The professional
      educational development of lecturers in oral hygiene could be influential in
      improving the profession within the country.

PMID- 23951790
TI  - Post-chemotherapeutic resolution of acute myeloid leukaemia-induced gingival
      enlargement: a case report.
AB  - INTRODUCTION: Leukaemia is a neoplastic dsorder characterized by an excessive
      proliferation of immature white blood cells and their precursors. Patients with
      this potentially fatal condition may often first present with gingival
      enlargement. Early diagnosis of the underlying condition and prompt referral for
      appropriate therapy, may be life-saving. CASE REPORT: A 27-year-old female was
      referred to the Department of Oral Medicine and Periodontology complaining of a
      generalised gingival enlargement that was aesthetically displeasing to her. She
      insisted on immediate surgical removal of the enlarged gingival tissue but, on
      counseling, agreed to have prior diagnostic tests performed. A full blood count
      suggested the presence of an underlying acute myeloid leukaemia. The patient was
      consequently referred to the Oncology Department for further investigation and
      management. The diagnosis was confirmed and the subsequent chemotherapeutic
      intervention was strikingly successful, leading to the complete resolution of the
      gingival enlargement. CONCLUSION: This paper emphasises the importance of a full
      diagnostic evaluation of all cases of gingival enlargement and immediate referral
      should a life-threatening condition be identified, such as, in the present case,
      acute myeloid leukaemia.

PMID- 23951791
TI  - HIV-associated oral lesions as an indicator for HAART failure: a review.
AB  - INTRODUCTION: HIV-associated oral lesions have been used as clinical indicators
      of HIV infection and/or HIV-disease progression. It is well established that
      there is a significant reduction in the incidence of most HIV-associated oral
      lesions in patients on HAART compared with the levels seen in HIV-seropositive
      patients not on HAART. However, the corollary, namely using the presence of HIV
      associated oral lesions as indicators of possible HAART failure, has not been
      sufficiently studied. METHODS: A literature search done in Pubmed, Ovid, Medline
      and Biomed Central databases identified as suitable for inclusion in this review
      four reports, which had considered HIV-associated oral lesions as clinical
      markers of HAART failure. RESULTS: The practicality of relying on the presence of
      HIV-associated oral lesions in the prediction of HAART failure was evaluated
      based on existing literature. Although it was suggested as an option in all four
      papers reviewed, the use of HIV-associated oral lesions as predictors of HAART
      failure has been recommended by only one of the studies. CONCLUSION: The use of
      HIV-associated oral lesions as predictors of HAART failure has been suggested.
      This has not been studied in the South African, or the African setting.

PMID- 23951792
TI  - Enhanced activity of demineralised bone matrix augmented with xenogeneic bone
      morphogenetic protein complex in rats.
AB  - INTRODUCTION: Demineralised bone matrix (DBM) is an allograft material widely
      used as a bone filler and bone graft substitute. DBM contains bone morphogenetic
      proteins (BMPs), which induce and regulate bone formation during embryogenesis
      and in postnatal life. AIMS AND OBJECTIVES: To investigate the osteoinductivity
      of DBM augmented with xenogeneic BMP-complex at different doses. MATERIALS AND
      METHODS: Rat DBM was augmented with BMP-complex purified from porcine diaphyseal
      bone. RESULTS: Dorsal subcutaneous implantation of 25 mg rat allogeneic DBM
      augmented with 0, 3, 6 and 12 mg BMP-complex per gram of DBM resulted in dose
      dependant up-regulation of bone formation on day 21, as scored histologically and
      biochemically. CONCLUSIONS: Allogeneic DBM can be augmented with xenogeneically
      sourced BMP-complex to improve DBM performance in vivo. This work demonstrates
      the potential of BMP-complex augmented DBM to induce new bone formation with
      improved parameters of bone formation.

PMID- 23951793
TI  - Characterising oral lesions in patients who presented with chronic
      vesiculobullous lesions during a 10-year period.
AB  - INTRODUCTION: Vesiculobullous lesions are a subset of lesons with an aetiologic
      spectrum that ranges from infection to aberrant mmune function. The bulk are
      chronic immune-mediated or autoimmune diseases in which inappropriate production
      of antibodies against auto-antigens results in the development of these
      conditions. METHODS: All departmenta patient records in the ten-year period were
      reviewed and those indicating a provisional diagnosis of oral chronic immune
      mediated lesions were included in the study. Simple descriptive statistics were
      used. Chronic immune-mediated conditions included were lichen planus, pemphigus
      vulgaris, benign mucous membrane pemphigoid, including cicatricial pemphigoid,
      bullous pemphigoid, erythema multiforme and systemic lupus erythematosus.
      RESULTS: The files of forty-five patients (12 males, 33 females) who had been
      provisionally diagnosed with immune-mediated oral lesions during a ten-year
      period, from 2001 to 2010, were identified. Of these, 22 (49%) recorded final
      diagnoses of chronic immune-mediated conditions. CONCLUSION: This paper
      characterises the oral lesions of chronic immune-mediated conditions diagnosed in
      patients attending the oral medicine clinic during a ten-year period.

PMID- 23951794
TI  - Comparison of chlorine dioxide and dichloroisocyanurate disinfectants for use in
      the dental setting.
AB  - AIM: The aim of this study was to compare the antimicrobial properties of a slow
      release noncorrosive chlorine dioxide with those of sodium dichloroisocyanurate
      to establish their possible use in the dental settings. MATERIALS AND METHODS:
      Disinfectant solutions were prepared according to manufacturers' instructions and
      tested against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC
      27853, Streptococcus mutans NCTC 1044, Candida albicans ATCC 90028, Bacillus
      subtilis ATCC 15244 spores, Mycobacterium tuberculosis ATCC 25177, Mycobacterium
      avium subsp. avium ATCC 25291 and Hepatitis B virus using the Standard
      quantitative suspension test. The shelf-lives of the disinfectants were also
      determined. RESULTS: Both disinfectants killed all the test organisms within 30
      seconds. B. subtilis spores were killed in 2 and 2.5 minutes by chlorine dioxide
      and sodium dichloroisocya nurate respectively. When diluted solutions of these
      disinfectants were stored in screw cap bottles, they retained their activity for
      at least 30 days. CONCLUSIONS: Chlorine dioxide and sodium dichloroisocyanurate
      containing disinfectants can be used in the denta settings for surfaces and heat
      sensitive instruments. However, chlorine dioxide is advantageous because it is
      non-corrosive and the effective concentration is lower than that recommended for
      sodium dichloroisocyanurate.

PMID- 23951795
TI  - Evaluation of Ki-67 and cyclin D1 expression in odontogenic keratocysts and
      orthokeratinised jaw cysts.
AB  - INTRODUCTION: Orthokeratinised jaw cyst (OJC) is an entity distinct from
      odontogenic keratocyst (OKC) that has not been fully characterised at the
      molecular level. AIM: To compare the proliferative activity of the epithelial
      linings of OKC and OJC immunohistochemically, using Ki-67 and cyclin D1 as
      markers of cellular proliferation and activity. METHODS: The total numbers of
      positively stained cells per 10 consecutive lengths of a light microscope
      calibration ruler were counted in each case (OKC, n = 15; OJC, n = 15) and the
      composite data were statistically compared. RESULTS AND CONCLUSIONS: OJC showed
      significantly fewer Ki-67 and cyclin D1 positive cells than OKC, a finding
      consistent with the clinically more indolent behaviour of the OJC. Ki-67
      expression was mainly detected in the suprabasal cell layers in OKC. Expression
      of Ki-67 was more uniform in OJC and notably without a significant predilection
      for the supra-basal compartment. The accumulation of Ki-67 positive cells supra
      basally in OKC raises the possibility that a process of asymmetrical cell
      division may be operational in OKC. Expression of Ki-67 and cyclin D1 differed
      significantly quantitatively and by distribution pattern in OKC and OJC
      respectively thereby suggesting that the presence of cyclin D1 protein in OKC and
      OJC may not necessarily reflect production of this molecule by cycling cells.

PMID- 23951796
TI  - Analysis of demographic data obtained from pathology records.
AB  - INTRODUCTION: Pathologists commonly analyse patient data obtained from pathology
      records. Such information is useful in that it might provide an indication of
      changing patterns of disease, or of the aetio-pathogenesis of a disease process,
      but such data is seldom standardised. AIM: To determine to what extent the lack
      of standardisation may influence the resultant data and the conclusions drawn.
      MATERIALS AND METHODS: Pathology reports of all cysts diagnosed from 1994 to 2004
      were retrieved. The diagnosis and site of the cyst, and the age, gender and race
      of patient were analysed. Comparative data from 1958 to 1992 was obtained from
      the text "Cysts of the oral regions". The data from the different periods was
      statistically compared. Only the four most common cysts were included: radicular,
      dentigerous, odontogenic keratocyst and nasopalatine duct cysts. RESULTS: There
      was no difference in frequency and site of cysts or in age of patients.
      Statistically significant differences were found in the gender and race
      comparisons. CONCLUSION: Do the differences reflect a changing pattern of disease
      or are they due to changes in the demographics of the patient pool from which the
      surgical specimens were obtained? We favour the latter. Awareness of the fact
      that data from either survey is not reliable due to lack of standardisation is
      pertinent to avoid drawing fundamental conclusions from such data.

PMID- 23951797
TI  - Application of the dental aesthetic index in the prioritisation of orthodontic
      service needs.
AB  - OBJECTIVE: The provision of orthodontic treatment to patients in government
      funded training institutions is a major challenge due to constrained budget and
      resource allocation. The Dental Aesthetic Index (DAI) has been used to estimate
      orthodontic treatment need and as a screening tool to determine treatment
      priority. The DAI focuses on aesthetics and therefore omits other malocclusion
      traits that might require orthodontic treatment. The aim of the study was to
      compare the application of the DAI with the influence other malocclusion traits
      not included in the DAI might have on the determination of the prioritisation of
      orthodontic service need. METHODS: Hundred-and-twenty pretreatment study models
      of orthodontic patients in the permanent dentition stage were selected from the
      archived records of the Department of Orthodontics, University of Limpopo, using
      a systematic sampling method. The study casts were assessed using the DAI. Other
      malocclusion traits not included in the DAI were also recorded. Descriptive
      statistics, the Pearson correlation coefficient, Chi-square values and t-tests
      were employed to analyse the data. P values less than or equal to 0,05 were
      considered statistically significant. RESULTS: The mean DAI score was 35.2.
      Normal or minor malocclusion was found in 19.1% of the sample, whilst 17.5% had
      definitive malocclusion, 21.7% severe malocclusion, and 41.7% showed handicapping
      malocclusion. Other malocclusion traits not included in the DAI were identified
      and these traits accounted for 21.6% of all traits recorded in the study (DAI
      malocclusion traits accounted for 78.4%). Two thirds of other malocclusion traits
      were accounted for in categories which the DAI had already prioritised for
      treatment. CONCLUSIONS: The study showed that the DAI can be used to prioritise
      orthodontic service needs and could be applied in government funded institutions.

PMID- 23951798
TI  - An evaluation of root resorption after orthodontic treatment.
AB  - Root resorption is commonly seen, albeit in varying degrees, in cases that have
      been treated orthodontically. In this retrospective study the objective was to
      compare the amount of root resorption observed after active orthodontic treatment
      had been completed with one of three different appliance systems, namely, Tip
      Edge, Modified Edgewise and Damon. The sample consisted of pre and post-treatment
      cephalograms of sixty eight orthodontic cases. Root resorption of the maxillary
      central incisor was assessed from pre- and post- treatment lateral ce phalograms
      using two methods. In the first, overall tooth length from the incisal edge to
      the apex was measured on both pre and post-treatment lateral cephalograms and
      root resorption was recorded as an actual millimetre loss of tooth length. There
      was a significant upward linear trend (p = 0.052) for root resorption from the
      Tip Edge Group to the Damon Group. In the second method root resorption was
      visually evaluated by using the five grade ordinal scale of Levander and Malmgren
      (1988). It was found that the majorty of cases in the sample came under Grade 1
      and Grade 2 category of root resorption. Statistical evaluation tested the extent
      of agree ment in this study between visual measurements and actual measurements
      and demonstrated a significant association (p = 0.018) between the methods.

PMID- 23951799
TI  - Do age and ethnicity play a role in the perception of facial profile
      attractiveness? A cross-sectional investigation.

PMID- 23951800
TI  - The role of the nose and cranial base in profile assessment: a morphological
      comparison between native African and Caucasian samples.
AB  - OBJECTIVE: The purpose of this research was to evaluate the position of the nose
      and how it affects clinical judgment of the face in a native African sample.
      METHODS: We considered the anatomic location of the nose with respect to the
      anterior cranial base (ACB) as well as to the maxillary lip, based on guidelines
      set down by Holdaway but slightly modified for purposes of this research.
      RESULTS: A comparison of the Shona to a Caucasian sample using selected
      parameters devised by Holdaway (pronasale to labrale superius) indicated that the
      Shona had a nose and ACB that were shorter than those of the comparative group of
      Caucasians. The short anterior cranial base was associated with a short and retro
      positioned nose which resulted in deceptively protrusive lips when assessed using
      Ricketts' profile line. Whilst there was no difference in nose depth between the
      groups, the nasal angle of the Shona was larger than that of Caucasians,
      indicating an up-tipped nose. CONCLUSION: The position of the nose has a bearing
      on orthodontic treatment planning. Understanding the facial morphology of the
      Shona led us to conclude that conventional soft tissue measurements may not be
      applicable to all patients who present for orthodontic treatment, and that it may
      be necessary to advise the patient to seek other avenues for satisfactory
      management, which, depending on the chief complaint, may include surgical
      augmentation of the nose and chin.

PMID- 23951801
TI  - On form and function in all-ceramic restorations.
AB  - All-ceramic restorations are achieving increasing popularity, partly because of
      the aesthetic demands of patients, but also because their increasing ease of
      fabrication and longevity compare favourably with the traditional plastic
      restorations in posterior teeth. The parallel development of cementation
      materials and bonding techniques has also improved longevity, although current
      evidence shows that posterior all-ceramic restorations have a slightly lower
      success rate than in anteriors, and the success rate falls with time. The purpose
      of this paper is to briefly review the evidence for the use of all-ceramic
      restorations particularly for posterior restorations on teeth, as well as to
      suggest that preparation form may need to change to take into account the
      properties of dental ceramics. In addition, a different approach to occlusal form
      is proposed, based on the evolution of form and function in dentitions, to
      suggest that the perfect reproduction of cusps and fissures may not be
      appropriate.

PMID- 23951802
TI  - Stabilising a planning guide in post-mandibulectomy prosthodontic rehabilitation.
AB  - Patients presenting with grafted reconstructions of the mandible often lack
      anatomical features that allow for the consistent placement of a diagnostic
      denture and planning guide. The mucosa covering the graft appears flat with no
      discernible ridge form. A method was therefore adapted to provide stability to a
      guide for the placement of implants. A diagnostic denture was constructed to the
      try-in stage and duplicated in clear acrylic, with radio-opaque markers placed
      into potential implant positions. Three mini-implants (Southern implants, Irene,
      SA) were then placed under local anaesthetic trans-mucosally into the bone graft
      at positions corresponding to teeth 46, 31 and 36. Access holes were created in
      the flanges of the diagnostic denture/planning guide to enable it to seat over
      the mini implant heads and to allow for final positioning. Auto-polymerising
      resin was then placed to cover each of these heads, thus stabilising the guide.
      The patient was then referred for a CT scan, to be taken with the planning guide
      in situ, and a surgical guide was made from the CT data, which also used the mini
      implants for orientation. At surgery, this ensured the optimal placement of the
      definitive implants, and the mini-implants could then be removed. This method
      thus provides enormous beneft to both the planning for, and the placement of,
      implants into grafted bone in mandibulectomy patients.

PMID- 23951803
TI  - Prosthodontic management of patients with amelogenesis imperfecta.
AB  - INTRODUCTION: Amelogenesis Imperfecta (AI) is an heterogenous genetic disorder
      that disturbs the developing enamel structure. This rare ectodermal defect leads
      to a variety of clinical manifestations due to agenesis, hypoplasia, and/or
      hypomineralisation of the enamel. AIMS AND OBJECTIVES: To describe the
      prosthodontic management of dental anomalies commonly associated with AI.
      METHODS: By using the classification of Witkop and Rao (1971), the variation in
      clinical presentation of the different Types of AI are illustrated and discussed,
      in particular Type I AI and Type 4 AI. RESULTS AND CONCLUSIONS: Early diagnosis
      and prosthodontic management as part of a multidisciplinary, patient-centred
      approach are key factors to treatment success. Treatment options to address the
      oral complications are influenced by modifying factors including age,
      socioeconomic status, type and severity of the disorder, and intraoral status at
      the time of treatment planning. Ultimately, management includes pain and
      infection control, provision of aesthetics and restoration of function which may
      lead to patient satisfaction, psychological well-being and an improved quality of
      life.

PMID- 23951804
TI  - Antibiotic prophylaxis for dental procedures: is it necessary?
AB  - INTRODUCTION: Guidelines regarding the prevention of infective endocarditis have
      recently been published by the British Society for Antimicrobial Chemotherapy in
      2006, the American Heart Association (AHA) in 2007 and the National Institute for
      Health and Clinical Excellence (NICE), UK, in 2008. These are contradictory, even
      though all are from developed countries. It is not known whether they are
      suitable for developing countries such as South Africa, nor is it known whether
      they are followed by general dental practitioners. AIMS AND OBJECTIVES: To
      conduct a survey amongst dental practitioners in South Africa to determine
      knowledge of the more recent AHA and NICE guidelines and the practices followed
      in antibiotic prophylaxis. METHOD: E-mails were sent to dentists registered with
      SADA requesting their participation in an internet-based survey. RESULTS: The
      limited response rate necessitated the pooling of the data, but it was felt they
      would be valuable if some trends emerged. Most (88%) of the 105 respondents were
      aware of the AHA guidelines, but only 55% knew of the NICE guidelines. However,
      few actually followed the recommendations and few correctly prescribed for
      patients allergic to penicillin. The large number of cases of rheumatic fever in
      this country implies that the AHA and NICE guidelines may not be appropriate.
      CONCLUSION: Despite the low sample size, the trends shown are of real concern.
      There is clearly a need for local guidelines, and once these are established,
      there is an urgent need to inform all dental practitioners of the appropriate
      prescription of prophylaxis for patients.

PMID- 23951805
TI  - The need for versatility in the prosthodontic treatment of maxillofacial defects.
AB  - The main objective of this study was to survey the different maxillofacial
      defects of patients who presented to the Wits Dental Hospital and to review the
      methods that have been used to rehabilitate these patients. Forty six patient
      records were retrieved from patients' files and from final year reports of
      prosthodontic postgraduate students. The data were used to determine the type of
      maxillofacial defects that these patients suffered from and the treatment that
      had been carried out. Duration and cost of treatment was also noted. The study
      showed that the majority of the patients' defects were caused by cancer
      resections, followed by trauma, clefts, burns, and infection. Most patients
      received conventional 'appropriatech' treatments such as the use of adhesive
      retained prostheses, whilst a small number received more sophisticated 'high
      tech' treatments of implant rehabilitation. The need for versatility in the
      prosthodontic treatment of maxillofacial defects.

PMID- 23951806
TI  - Dental ethics case 24. Non-therapeutic cosmetic treatments including botox.

PMID- 23951807
TI  - Chivalry and fairplay.

PMID- 23951808
TI  - SADA communique.

PMID- 23951809
TI  - The Wentworth Foundation: a community-service born out of necessity.

PMID- 23951810
TI  - Diffuse peripheral odontogenic fibroma with concomitant plasma cell gingivitis--a
      case report and literature review.
AB  - Peripheral odontogenic fibroma is a rare odontogenic neoplasm that occurs on the
      gingiva, and cases of diffuse gingival involvement are most uncommon. An example
      of such a case compounded by superimposed plasma cell gingivtis is presented
      together wth a review of the literature.

PMID- 23951811
TI  - Compliance and satisfaction in the orthodontic patient.

PMID- 23951812
TI  - The effect of overbooking on idle dental chair capacity in the Pretoria region of
      the Gauteng Oral Health Services.
AB  - An analysis of annual reports revealed that on average 20% of patient
      appointments with oral hygienists in the Department of Health in the Pretoria
      region were not utilised due to patient noncompliance (i.e. broken appointments).
      Many solutions have been considered to address the high rate of noncompliance and
      the resulting idle chair capacity. One solution selected to overcome some of the
      negative consequences of broken appointments was deliberate overbooking. The aim
      of our study was to determine the effect of overbooking on idle dental chair
      capacity by measuring the utilisation rate over a three month period (July to
      September) after 25% overbooking was introduced in the Pretoria region. A
      statistical analysis was conducted on our results to determine an overbooking
      rate that would ensure full utilisation of the available dental chair capacity.
      The available time units over the three month study period amounted to 1365,
      allocated to 1427 patients resulting in an overal overbooking rate of 4.54%. The
      overall utilisation rate was found to be 79.2%. The calculated regression line
      estimated that there would be full utilisation of dental chair capacity at an
      overbooking rate of 26.7%. Overbooking at the levels applied in this study had a
      minimal overall effect on idle dental chair capacity. Our results confirm the
      need for careful planning and management in addressing noncompliance. In a manner
      similar to the clinical situation, organisational development requires a correct
      diagnosis in order that an appropriate and effective intervention may be
      designed.

PMID- 23951813
TI  - Dentists' prescribing--some questions asked.

PMID- 23951814
TI  - Medicines and related substances act.

PMID- 23951815
TI  - Oral medicine case book 42--pemphigus vulgaris.

PMID- 23951816
TI  - General practitioner's radiology case 105. Eruption cysts.

PMID- 23951817
TI  - Dental ethics case 25: the drug-abusing patient--what are my ethical obligations
      to treat?

PMID- 23951818
TI  - A 4-year prospective study on long-term complications of type 2 diabetic
      patients: the Thai DMS diabetes complications (DD.Comp.) project.
AB  - OBJECTIVE: To assess the clinical course of long-term diabetic complications;
      diabetic retinopathy, nephropathy, and foot problems in Thai patients with type 2
      diabetes. MATERIAL AND METHOD: Patients with type 2 diabetes were followed for
      four years between March 2006 and September 2010. Seven hospitals in all levels
      of care under the Ministry of Public Health Thailand were included in the present
      study. A physical examination and a diabetic complications assessment were
      performed each year during the study period, by physician specialists in the
      related areas. RESULTS: Among 1,120 patients who participated in the present
      study, 705 (62.95%) patients completed the 4-year follow-up time. There were 88
      (7.86%) patients reported deaths during the present study period. The mean age
      was 59.14 +/- 10.12 years. The average duration of diabetes was 7.30 +/- 6.14
      years. Approximately 57.32% of patients had a family history of diabetes. The
      average plasma glucose level and HbA1C were 153 to 160 mg/dl and 8.25 to 8.75%.
      Moreover less than one-fourth of patients had HbA1C below 7%. The prevalence for
      diabetic retinopathy and nephropathy were approximately 23.7% and 38.3%. In
      addition, more than 15% of patients had diabetic foot problems, loss of
      protective sensation and pedal pulse deficit. Finally, the incidence rates were
      80.1 per 1,000 person-years (95% CI 69.7, 91.8) for diabetic retinopathy, and
      91.1 per 1,000 person-years (95% CI 78.8, 105.1) for diabetic nephropathy
      CONCLUSION: Problems regarding poor diabetes control exist in Thai diabetes
      patients. It results in high prevalence and incidence of diabetic complications.
      As such, it is crucial to establish the country's diabetes management plan as
      well as evaluate the long-term complications in diabetic patients annually, in
      order for patients to receive the benefits of early treatment and prevent further
      complications.

PMID- 23951819
TI  - Factors predicting sputum smear conversion and treatment outcomes in new smear
      positive pulmonary tuberculosis.
AB  - BACKGROUND: Epidemiological studies indicated that the proportion of TB patients
      who remained smear-positive after two months of treatment could be greater than
      20%. The lack of smear conversion in the second month of treatment was one of the
      predictors of treatment failure and relapse. OBJECTIVE: To determine factors
      associated with the persisting positive smear after two months of treatment and
      its value in predicting treatment failure. MATERIAL AND METHOD: A 3-year
      retrospective cohort study was conducted in a 1,200-bed government hospital in
      Thailand New smear-positive tuberculosis patients who had pretreatment drug
      susceptibility test, the result of 2-month sputum smear and treatment outcomes
      were selected. The pretreatment drug susceptibility pattern and statistically
      differences on variables between groups of patients were described RESULTS: Three
      hundred fifty six patients were included in the present study. The level of
      pretreatment isoniazid resistance and multi-drug resistance were 13.8% and 3.1%
      respectively. Factors associated with the 2-month positive smear were male sex,
      high initial sputum acid-fast bacilli grades, and cavitary diseases. The presence
      of human immuno-deficiency virus infection, drug resistance and the 2-month
      positive smear were significantly associated with treatment failure. CONCLUSION:
      Male sex, high initial sputum acid-fast bacilli grades, and cavitary diseases
      were factors associated with the 2-month positive smear and increasing risk of
      treatment failure.

PMID- 23951820
TI  - Duration and practices of television viewing in Thai infants and toddlers.
AB  - BACKGROUND: Television viewing is discouraged in infants; however its magnitude
      and pattern in Thailand is still unknown MATERIAL AND METHOD: Data on magnitude
      of TV viewing and viewing practices from 4,157 children in Prospective Cohort of
      Thai Children were obtained between 2001 and 2005. RESULTS: At 1, 2, 2.5, and 3
      years of age, the percentage of children watching TV was 77%, 90%, 92%, and 95%,
      respectively. Viewing duration also increased with age from 10 minutes/day at 1
      year to 60 minutes/day at 3 years. Bangkok children spent double the screen time
      than children in other provinces. The most popular programs were cartoons and
      entertainment while 4% to 7% watched children programs. CONCLUSION: Most children
      in this cohort were exposed to TV by three years of age.

PMID- 23951821
TI  - Neonatal morbidity and mortality for repeated cesarean section vs. normal vaginal
      delivery to uncomplicated term pregnancies at Srinagarind Hospital.
AB  - OBJECTIVE: To evaluate the morbidities and mortality of neonates delivered by
      elective repeated cesarean section vs. normal vaginal delivery among women with
      uncomplicated term pregnancies. MATERIAL AND METHOD: A retrospective descriptive
      study was done between January 2009 and December 2011 to determine the
      morbidities and mortality among uncomplicated term pregnancies at Srinagarind
      Hospital. Three hundred seventy two neonates delivered by elective repeated
      cesarean section vs. 1,581 by normal vaginal delivery. RESULTS: A significantly
      greater number of neonates in the elective repeated cesarean section group
      required oxygen for neonatal resuscitation compared to neonates in the normal
      vaginal delivery group (37.6% vs. 20.9%, p < 0.001). Neonates delivered by
      elective repeated cesarean section were more frequently admitted to the neonatal
      intensive care unit (1.1% vs. 0%, p < 0.001) and had longer hospital stays (4.56
      +/- 2.45 vs. 4.07 +/- 1.44 days, p < 0.001). The latter not only had a higher
      rate of respiratory distress syndrome (0.8% vs. 0%, p < 0.001) and transient
      tachypnea of the newborn (3.2% vs. 0.3%, p < 0.001), which required more
      respiratory support, they also had a higher rate of infection (2.4% vs. 0.8%, p <
      0.05) than neonates delivered by normal vaginal delivery. Neonates born by normal
      vaginal delivery, however had more birth trauma and hyperbilirubinemia than
      neonates born by elective repeated cesarean section (8.8% vs. 2.4%, p < 0.001 and
      31.8% vs. 22.6%, p < 0.05, respectively). There was no difference in the
      mortality rate between the groups. CONCLUSION: Even among uncomplicated term
      pregnancies, cesarean section is associated with more neonatal respiratory
      morbidity and sepsis while those delivered by normal vaginal delivery tend to
      have a higher rate of birth trauma and hyperbilirubinemia. Clinicians should
      therefore be concerned about the route of delivery and the probability of
      negative neonatal outcomes.

PMID- 23951822
TI  - Catheter-directed thrombolysis for acute limb ischemia caused by native artery
      occlusion: an experience of a university hospital.
AB  - OBJECTIVE: To evaluate the efficiency and complications of catheter-directed
      thrombolysis (CDT) of acute limb ischemia (ALI) resulting from thromboembolic
      occlusion. MATERIAL AND METHOD: A retrospective study of CDT was carried out in
      patients with acute thromboembolic arterial occlusion and marginally threatened
      ischemia of the extremities between February 2006 and December 2011. After the
      tip of the angiographic catheter was placed within the blood clot, recombinant
      tissue plasminogen activator (rt-PA) was used for thrombolysis. The CDT procedure
      included an initial bolus injection of high dose rt-PA (5-15 mg) followed by a
      tapering of infusion rate (1-2 mg/hour) through the catheter Primary outcome was
      1-year amputation free survival rate and mortality rate. Secondary outcome
      included technical and clinical success rates, time to lysis, and complication
      rate. The complete reestablishment of the occluded arteries without major
      amputation and death was considered successful treatment. RESULTS: Thirty-seven
      patients (30 males and 7 females) with the mean age of 55.6 years (range, 27-86
      years) were enrolled in the present study. The number of acute arterial occlusion
      was 23 (62.2%) of acute arterial embolism and 14 (37.8%) of acute arterial
      thrombosis. Embolism involved two aortic bifurcations, two iliac arteries, five
      femoral arteries, 13 popliteal arteries, and one both popliteal arteries. The
      sites of thrombosis were one of aorto-iliac segment, three of iliac artery, five
      of femoral artery, three of popliteal artery, one of bilateral popliteal, and one
      of tibio-peroneal artery. The mean duration of completed infusions was 21.29
      hours (range, 2-58 hours). Successful adjunctive percutaneous intervention or
      arterial bypass was performed in seven patients (18.9%) whose stenotic lesions
      were disclosed following CDT The 30-day perioperative mortality and 30-day
      amputation-free survival rates of the patients treated by CDT were 10.8% (4 of 37
      patients) and 86.5% (32 of 37 patients) respectively. Both 6-month and 1-year
      amputation free survival rate were 78.4% (29/37). Technical success rate was
      75.7% (28/37) whereas clinical success was 86.5% (32/37). Technical success rate
      was 80.0% (28/35) if ischemic symptom onset was no longer than six weeks. The 30
      day major complications included two patients (5.4%) requiring more than four
      units of blood transfusion for access site hematoma, two (5.4%) large fatal
      intracerebral hemorrhages, one (2.7%) small intracerebral hemorrhage, one (2.7%)
      acute embolic stroke, and one (2.7%) death of multiple organ failure following
      conversion to surgical revascularization. Minor complications were distal
      thromboembolization in one patient (2.7%), small hematoma in seven patients
      (18.9%), and pseudoaneurysm in one patient (2.7%). CONCLUSION: CDT is an
      effective armamentarium to salvage the ischemic limb resulting from acute
      embolism and acute thrombosis of native artery. However bleeding complication is
      a major problem of this treatment. Although CDT is usually applied for ALI
      patients with ischemic symptom onset less than 14 days, it also provides
      technical success for those with the symptom onset between the second and the
      sixth weeks.

PMID- 23951823
TI  - Clinical outcome of the patients treated surgically for spontaneous intracerebral
      hematoma at Sawanpracharak Hospital.
AB  - OBJECTIVE: To study the relationship of factors associated with clinical outcome
      in surgical groups of spontaneous intracerebral hematoma patients (SICH).
      MATERIAL AND METHOD: The data were retrospectively collected from surgically
      treated SICH patients who had surgery at Sawanpracharak Hospital between October
      2006 and September 2009. Risk factors (heart disease, previous stroke,
      hypertension, diabetes mellitus (DM), hyperlipidemia, obesity, smoking, alcoholic
      consumption, and family history), Glasgow Coma Scale (GCS), hematoma volume,
      midline shift (MS), intraventricular bleeding (IVH), hydrocephalus, convulsion,
      tracheostomy, pneumonia, rebleeding, operating time, and intraoperative blood
      loss were studied. RESULTS: Throughout the study period, 380 patients with SICH
      underwent surgical treatment. Factors that were statistically significant related
      to outcome of SICH were age (p < 0.001), diabetes mellitus (p < 0.001), smoking
      (p = 0.003), alcoholic consumption (p = 0.001), Glasgow Coma Scale (p < 0.001),
      hematoma volume (p < 0.001), midline shift (p < 0.001), intraventricular bleeding
      (p < 0.001), hydrocephalus (p < 0.001), pneumonia (p < 0.001), rebleeding (p =
      0.006), operating time (p < 0.001), and intraoperative blood loss (p = 0.008).
      After logistic regression analysis was done, factors that were statistically
      significantly related were Glasgow Coma Scale 3 to 8 [OR 6.03 (3.09-11.75); p <
      0.001], Glasgow Coma Scale 9 to 12 [OR 3.29 (1.87-5.77); p < 0.001],
      intraventricular bleeding [OR 2.33 (1.37-3.98); p = 0.002], pneumonia [OR 1.62
      (1.00-4.23); p = 0.049], rebleeding [OR 2.30 (1.04-5.08); p = 0.040], operating
      time greater than two hours [OR 3.05 (1.11-8.34); p = 0.030], and midline shift
      greater than 10 mm [OR 2.07 (1.04-3.57); p = 0.038]. CONCLUSION: Outcome of
      surgical treatment of SICH in the present study were related to age, diabetes
      mellitus, smoking, alcoholic consumption, Glasgow Coma Scale 3 to 8 and 9 to 12,
      hematoma volume, midline shift greater than 10 mm, intraventricular bleeding,
      hydrocephalus, pneumonia, rebleeding, operating time greater than two hours, and
      intra operative blood loss.

PMID- 23951824
TI  - Factors influencing the outcome of decompressive craniectomy used in the
      treatment of severe traumatic brain injury.
AB  - OBJECTIVE: To evaluate risk factors that influences the outcome of decompressive
      craniectomy (DC) in severe traumatic brain injury patients. MATERIAL AND METHOD:
      The authors' retrospective review of data collected from 826 severe traumatic
      brain injury patients admitted to the Chiang Mai University Hospital between
      January 1, 2006 and December 31, 2008. During this period, 159 of 826 patients
      (19.25%) underwent DC and the craniectomy size was not smaller than a fronto
      temporo-parietal or a bifrontal bone flap. Data collected included demographics,
      pre- and post-operative Glasgow coma scores (GCS), timing of surgery,
      complications, and Glasgow outcome score (GOS) at discharge and six months after
      surgery. At our institution, patients are managed using the Brain Trauma
      Foundation guidelines. RESULTS: One hundred fifty nine patients were identified,
      130 (81.76%) male and 29 (18.23%) female. One hundred twenty two patients were
      operated within the first 24 hours after admission. Overall mortality rate was
      44.65%. The survival group was younger (30.73 years vs. 43.46 years, p < 0.001)
      and had a higher pre-craniectomy GCS (6 vs. 5, p = 0.002). Of the 88 survivors,
      favorable outcome was achieved in 21 patients (13.20%) at discharge and increased
      to 38 patients (23.89%) at six months after surgery. Those with favorable outcome
      were younger (25.43 years vs. 38.35 years, p = 0.001) and had a higher pre
      craniectomy GCS (p = 0.013). CONCLUSION: Younger age group patients and higher
      pre-operative GCS are two factors that influence the outcome of DC. Early
      decompressive craniectomy in patients with higher GCS may result in better
      functional outcomes.

PMID- 23951825
TI  - The efficacy and safety of on-demand Elonza; a generic product of sildenafil in
      Thai men with erectile dysfunction.
AB  - OBJECTIVE: To evaluate the efficacy and safety of Elonza (generic product of
      sildenafil) 100 mg, a phosphodiesterase type 5 (PDE5) inhibitor, in Thai men with
      erectile dysfunction (ED). MATERIAL AND METHOD: This prospective, Cohort study
      was conducted for eight weeks. Two hundred ten male patients, older than 20 years
      of age with ED were enrolled to receive generic product of sildenafil 100 mg
      taken as needed. Efficacy is evaluated through the International Index of
      Erectile Function (IIEF) scores for the five separate response domains, erectile
      function, orgasmic function, sexual desire, intercourse satisfaction, and overall
      satisfaction domain. RESULTS: After sildenafil administration, erectile function
      domain scores were significantly increased from baseline, 5.02 (p < 0.001) and
      7.19 (p < 0.001) in one month and two months, respectively. Intercourse
      satisfaction domain scores and overall satisfaction domain scores were
      significantly increased from baseline, 3.17 (p < 0.001) and 1.74 (p < 0.001) in
      two months, respectively. Most treatment emergent adverse events were mild or
      moderate. The most frequent treatment-emergent adverse events were flushing
      (13.2%), nasal congestion (9.8%), abnormal vision (4.9%), headache (4.4%),
      dizziness (2.9%), and dyspepsia (0.5%). CONCLUSION: Elonza, a generic product of
      sildenafil, was an effective and well-tolerated treatment for ED in Thai men.

PMID- 23951826
TI  - Performance of optical coherence tomography for distinguishing between normal
      eyes, glaucoma suspect and glaucomatous eyes.
AB  - OBJECTIVE: Evaluate the diagnostic performance of spectral-domain optical
      coherence tomography (OCT) parameters to distinguish between healthy, glaucoma
      suspect, and glaucomatous eyes. MATERIAL AND METHOD: Forty-eight eyes of
      glaucoma, 48 glaucoma suspect eyes, and 35 healthy eyes were included. The
      circumpapillary and macular retinal nerve fiber layer (RNFL) thickness were
      measured using the Cirrus OCT (Carl Zeiss Meditec, Inc., Dublin, CA, USA). One
      way analysis of variance was used to compare the different parameters among
      groups. Calculating areas under receiver operating characteristic (AROC) curves
      evaluated the discriminating power of each parameter RESULTS: The average
      circumpapillary RNFL thickness in normal, glaucoma suspects, and glaucomatous
      eyes were 100.31 +/- 7.69 microm, 90.27 +/- 9.22 microm, and 71.40 +/- 13.08
      microm, respectively (p < 0.001). The largest AROC curve among the
      circumpapillary parameters was the inferior quadrant thickness (0.974, p <
      0.001). The macular volume had the largest AROC curves (0.898, p < 0.001) of all
      macular parameters. For glaucoma suspect eyes versus early glaucomatous eyes, the
      best value of circumpapillary parameters was inferior quadrant thickness (0.835,
      p < 0.001). Among the macular parameters, the best value was the macular cube
      volume (0.766, p < 0.001). CONCLUSION: Circumpapillary parameters have better
      diagnostic performance than macular parameters especially the inferior quadrant
      thickness that has the best discriminating power

PMID- 23951827
TI  - Pre-operative prediction of cervical nodal metastasis in papillary thyroid cancer
      by 99mTc-MIBI SPECT/CT; a pilot study.
AB  - OBJECTIVE: Papillary thyroid cancer has a high prevalence of cervical nodal
      metastasis. There is no "gold standard" imaging for pre-operative diagnosis. The
      aim of the present study was to assess the accuracy of pre-operative 99mTc-MBI
      SPECT/CT in diagnosis of cervical nodal metastasis in patients with papillary
      thyroid cancer MATERIAL AND METHOD: Fifteen patients were performed 99Tc-MlBI
      SPECT/CT pre-operatively. Either positive pathological report of neck dissection
      or positive post-treatment I-131 whole body scan with SPECT/CT of neck was
      concluded for definite neck metastasis. The PPV, NPV, and accuracy of 99mTc-MIBI
      SPECT/CT were analyzed. RESULTS: The PPV NPV and accuracy were 80%, 88.89%, and
      85.71%, respectively. 99mTc-MIBI SPECT/CT could localize the abnormal lymph nodes
      groups correctly in most cases when compared with pathological results. However
      the authors found one false positive case with caseating granulomatous
      lymphadenitis and one false negative case with positive post-treatment 1-131
      whole body scan with SPECT/CT of neck on cervical nodes zone II and IV
      CONCLUSION: 99mTc-MIBI SPECT/CTseem promising for pre-operative staging of
      cervical nodal involvement in patients with papillary thyroid cancer without the
      need of using iodinated contrast that may complicate subsequence 1-131 treatment.
      However, false positive result in granulomatous inflammatory nodes should be
      aware of especially in endemic areas. 99mTc-MIBI SPECT/CT scan shows a good
      result when compared with previous study of CT or MRI imaging. The comparative
      study between different imaging modality and the extension of neck dissection
      according to MIBI result seems interesting.

PMID- 23951828
TI  - Detection of recurrent colorectal cancer by 18F-FDG PET/CT comparison with
      contrast enhanced CT scan.
AB  - OBJECTIVE: To evaluate diagnostic performance of 18F-FDG PET/CT in assessment of
      recurrence colorectal cancer after treatment in Siriraj Hospital. MATERIAL AND
      METHOD: The authors retrospectively studied 48 treated colorectal cancer patients
      with suspected recurrence who underwent 18F-FDG PET/CT and contrast-enhanced CT
      (CECT). Clinical information, image follow-up for at least one year, and
      pathological reports of the patients were reviewed for gold standard RESULTS:
      Recurrent or metastatic disease was found in 36 of 48 patients. Calculated
      sensitivity, specificity and accuracy of 18F-FDG PET/CT were 94.4%, 66.7%, and
      87.5%. 18F-FDG PET/CT can reduce false positive results of CECT in six patients,
      thus specificity of 18F-FDG PET/CT was statistically significantly better than
      that of CECT. Using lesion-based analysis with 65 recurrent sites and 26 non
      recurrent lesion, 18F-FDG PET/CT showed better sensitivity 87.7%, specificity
      61.5%, and accuracy 80.2 than CECT without statistical significance. CONCLUSION:
      18F-FDG PET/CT overall showed higher sensitivity, specificity, and accuracy than
      CECT.

PMID- 23951829
TI  - Real-world outcomes of different treatments in the management of patients with
      HER-2 positive breast cancer: a retrospective study.
AB  - OBJECTIVE: To investigate the treatment outcome in terms of relapse free survival
      and overall survival, and explore the determinants of the clinical outcome in HER
      2/neu positive breast cancer patients who received or not received adjuvant
      trastuzumab. MATERIAL AND METHOD: The authors reviewed retrospectively of newly
      diagnosed non-metastatic breast cancer patients at the Faculty of Medicine,
      Chiang Mai University between January 2004 and December 2007. Comparisons were
      made between the two cohorts, women who did not receive adjuvant trastuzumab (100
      patients) and women who received adjuvant trastuzumab (14 patients). RESULTS: The
      median follow-up time was 4.7 years. Four-year relapse-free survival (RFS) and
      overall survival (OS) in patients receiving trastuzumab was 92.3% and 100%,
      respectively. In the cohort of HER-2 positive patients who did not receive
      trastuzumab, the 4-year RFS in this group was 68.2% and 4-year OS was 87.8%. The
      difference was not statistically significant between the 4-year RFS rates (p =
      0.103) and the 4-year OS rates (p = 0.214). By multivariate Cox regression
      analyses, only nodal status was identified as the independent predictors for
      superior RFS (hazard ratio 2.93; 95% CI, 1.07 to 5.88; p = 0.034) and none of the
      clinical parameters were significant predictors for 4-year overall survival.
      CONCLUSION: A hospital-based analysis of adjuvant Trastuzumab use in our center
      does not demonstrate the different treatment outcome. However there is a trend of
      favorable outcome in the group receiving adjuvant trastuzumab.

PMID- 23951830
TI  - Value of diffusion tensor imaging in differentiating high-grade from low-grade
      gliomas.
AB  - OBJECTIVE: To determine the usefulness of diffusion tensor imaging (DTI) in
      differentiating high-grade glioma (HGG) from low-grade glioma (LGG). MATERIAL AND
      METHOD: Patients with cerebral gliomas underwent conventional MRI and DTI before
      surgery. All proven pathologies were classified into two groups, i.e. LGG and
      HGG. The authors measured fractional anisotropy (FA) and apparent diffusion
      coefficient (ADC) values in region of interest (ROI) including solid tumoral
      region, necrotic region, peritumoral edema, contralateral normal appearing white
      matter (NAWM) and normal corpus callosum as well as calculated ADC ratios.
      Pairwise comparisons were performed by using the t-test. The ROC curves of
      imaging parameters were employed to determine the best parameter for
      differentiating the two entities. RESULTS: Forty-three patients with cerebral
      gliomas, 17 with LGG and 26 with HGG, no statistical significant difference
      between LGG and HGG using mean FA values in each ROI. The ADC and minimal ADC
      values of solid tumoral region and peritumoral edema, the ADC and minimal ADC
      ratios of solid tumoral region are statistical significant to differentiate HGG
      from LGG, p < 0.05. The ratio ADC solid tumoral region to normal corpus callosum
      had highest predictive accuracy to differentiate the two entities with AUC of
      0.74. CONCLUSION: The ADC value, minimal ADC value, and ADC ratios of solid
      tumoral region appeared to be useful for differentiating HGG from LGG.

PMID- 23951831
TI  - Benefits and constraints in screening for non-communicable diseases in the rural
      area of Thailand's northeast.
AB  - OBJECTIVE: To investigate the benefits and constraints of a screening attempt as
      initiated by the Ministry of Public Health (MoPH) measuring over-nutrition,
      hypertension and type 2 diabetes mellitus (T2DM) undertaken by the local health
      officials on sub-district level. MATERIAL AND METHOD: Capillary blood glucose
      (CBG), body mass index (BMI), blood pressure, and history of type 2 diabetes
      mellitus (T2DM) of first degree relatives was assessed following the direction of
      the Ministry of Public Health (MoPH) by the local health officials. RESULTS: The
      proportions of obesity, hypertension, and T2DM from 7,698 villagers were about
      35%, 20%, and suspected to be 9%, respectively. This was similar to previous
      investigations except for the history of T2DM of first-degree relatives, which
      strongly relates to elevated CBG levels. A high percentage of missing value was
      recognized for all variables. CONCLUSION: The screening of non-communicable
      disease program executed by the lower level of the health delivery system is an
      achievement by itself It can detect new cases of diseases. However incompleteness
      of variables is a constraint observed due to high workload of the health staff To
      decrease the burden of the public health staff and the curative sector and
      increase accuracy, the proportion of the population eligible for screening should
      be restricted to a higher age, being obese, and having a first-degree relative
      with diabetes mellitus.

PMID- 23951832
TI  - Effects of a cigarette smoking prevention program among junior high school
      students in north-east Thailand: a pilot survey.
AB  - OBJECTIVE: Evaluate the implementation of a smoking prevention program via a
      questionnaire. Both knowledge and attitudes toward smoking behavior and smoking
      cessation were also investigated MATERIAL AND METHOD: An experimental study was
      conducted between October 2011 and July 2012. Two hundred twenty six school
      students from Mathayom 1 to 6 participated into the present study. They were
      divided into either a study group (n = 99) or a control group (n = 127).
      Participants in the study group underwent two days of a smoking prevention
      program and the control group was not subjected to this program. Both groups
      completed a questionnaire containing questions related to the knowledge of the
      dangers of cigarette, attitudes toward smoking behavior, and smoking cessation at
      three different stages, pre-program, immediate post-program, and one month post
      program. All data was analyzed via statistical methods. RESULTS: Participants in
      the study group were smokers and non-smokers, aged between 13 and 15, studied in
      Mathayom 1 to 6. It was reported that 75% of smokers had tried to quit smoking at
      least once. For those who quit smoking successfully, 83.6% sought advice from
      their families. Regarding knowledge related to the dangers of cigarettes, the
      study group had significantly higher scores than the control group at the three
      different stages (pre-program, immediate post-program, and one month post-program
      p = 0.001, 0.001, and 0.024 respectively). The attitudes toward smoking cessation
      behavior between the groups were significantly different at the three different
      stages (p = 0.03, 0.01, and 0.001 respectively). The influential factor
      significantly related to decision-making related to quitting cigarettes was
      advice, especially from friends andfamilies (p < 0.05). CONCLUSION: School
      students aged between 13 to 15 years of age studying in Mathayom 3 (grade 9)
      represented the majority of smokers. The study found the smoking cessation
      prevention program was able to improve knowledge of the dangers of cigarettes.
      After the completion of the program, the effect offactors on their lives such as
      medical conditions, social norms, andfriends and families made smokers realize
      the importance of quitting smoking.

PMID- 23951833
TI  - Transfemoral temporary aortic balloon occlusion assisting open repair for
      ruptured abdominal aortic aneurysms.
AB  - The mortality rate of ruptured abdominal aortic aneurysm (rAAA) is still high
      despite an advance in surgical technology and critical care. The authors report
      three patients who had successful open repairs of rAAA assisted by transfemoral
      temporary aortic balloon occlusion. Before the operation, these patients had
      severe abdominal pain with hypotension. An aortic balloon occlusion catheter was
      introduced into the abdominal aorta under fluoroscopy at pararenal level, which
      was accessed from the right common femoral artery under local anesthesia. After
      balloon inflation, a rapid increase in arterial blood pressure was found and
      general anesthetic induction was started. Finally, open repair of rAAA was
      successfully carried out with rapid proximal neck control by aortic balloon
      palpation. All the patients made an uneventful recovery during the postoperative
      period and were discharged on day 16, day 8, and day 17 respectively. CONCLUSION:
      Transfemoral temporary aortic balloon occlusion is an effective strategy in rapid
      proximal aortic control before a conventional open repair of rAAA. It provides
      immediate hemostasis resulting in stabilized blood pressure before and during
      anesthetic induction, and facilitated aortic neck identification.

PMID- 23951834
TI  - Upper gastrointestinal bleeding from gastric splenosis; A case report and
      literature review.
AB  - Splenosis is a common condition found in a case that has a history of splenic
      trauma or splenectomy. It is usually a non-significant condition in clinical
      practice. However, splenosis can give rise to some complications including
      gastrointestinal hemorrhage as in the present case. The authors report here a
      case of gastric splenosis presenting with active upper gastrointestinal
      hemorrhage that was eventually managed with surgical resection, and the
      literature regarding splenosis was reviewed.

PMID- 23951836
TI  - Talking about compliance.

PMID- 23951835
TI  - 131I-rituximab treatment in patient with relapsed non-Hodgkin's lymphoma: the
      first case report in Thailand.
AB  - Radioimmunotherapy (RIT) with 131-rituximab is a safe and effective treatment in
      patients with relapsed, refractory follicular lymphoma. The authors demonstrated
      the first case of 131-rituximab treatment in the patient with relapsed non
      Hodgkin's lymphoma (NHL) in Thailand. There was no immediate complication after
      treatment. Impressive treatment response occurred.

PMID- 23951837
TI  - Footwear in focus.

PMID- 23951838
TI  - Innovation meets performance.

PMID- 23951839
TI  - Get your construction solutions from construction solutions.

PMID- 23951840
TI  - How to keep waste in its place.

PMID- 23951841
TI  - Adjusting to a new standard.

PMID- 23951842
TI  - Creating a fall protection plan and a safer workplace.

PMID- 23951843
TI  - Moving selection to the top of the hierarchy.

PMID- 23951844
TI  - The more things change, the more they stay the same when your data shows a
      troublesome.

PMID- 23951845
TI  - Ensuring compliance: tools for the EH&S toolbox.

PMID- 23951846
TI  - Wearing the safety brand.

PMID- 23951847
TI  - Top five ways to reduce fall hazard risk.

PMID- 23951848
TI  - Have a false sense of security.

PMID- 23951849
TI  - Industrial vacuums: your first line of defense against hazardous materials.

PMID- 23951850
TI  - Filling a critical need for training.

PMID- 23951851
TI  - Protecting workers from risks associated with nanomaterials: Part I, Exposure
      assessment.

PMID- 23951852
TI  - Lean Behavior-Based Safety: a natural evolution.

PMID- 23951853
TI  - [Maintaining opioid abstinence long after inpatient treatment with opioid
      substitution in an addictology hospital unit].
AB  - OBJECTIVES: Assess the effectiveness of hospital detoxification of opiate
      substitution treatment (OST) in patients who failed to withdraw as outpatients.
      METHODS: Retrospective study, conducted among patients admitted for withdrawal of
      OST in an addiction unit between 2005 and 2011. Referent physicians were
      interviewed about outcomes at M2, M3, M6 and M12. RESULTS: 47 patients were
      hospitalized for OST withdrawal. The opioid abstinence rates at 2, 6 and 12
      months were 60, 28 and 21 %. No death occurred within 12 months after withdrawal.
      The only variables significantly associated with the M3 opioids abstinence were :
      age at admission and among the patients admitted for buprenorphine withdrawal, a
      low dose of buprenorphine at admission. CONCLUSION: OST withdrawal in a
      specialized inpatient unit among patients with failure of outpatient withdrawal
      appears as an option, with an efficacy at least comparable to other methods of
      detoxification. It allows a comprehensive care and to prevent the risk of
      overdose.

PMID- 23951854
TI  - [Focus on planning the supply of physicians in Belgium].
AB  - BACKGROUND: The planning of human medical resources has been in progress since
      1996. The aim of this paper is to describe the process which occurred in Belgium
      and to point out its assets and limits. METHODS: Literature review, analysis of
      the Belgian legislation at national and community (Flemish and French-speaking)
      level and analysis of the projection model. RESULTS: In Belgium, planniing is
      performed at two different levels of power. Firstly, the federal State determines
      the number of physicians who will access to the professional titles enabling them
      to obtain reimbursement of care by Health Funds. It is sustained by a supply
      projection type " stock and flows", an assessment of the number of required
      physicians (including healthcare expenditures by age and sex) and the purpose of
      equalizing Dutch-speaking and French-speaking medical densities. Secondly,
      Communities, are responsible for training and, as such, are organizing the
      selection at this level : entrance examination in the North and various selection
      procedures (now repealed) in the South. CONCLUSION: Worldwide, the managers of
      medical planning are faced with decisions related to appropriate numbers for
      human resources, given population needs, use of services and professional
      productivity. They have to address concerns from medical surplus to shortage. The
      case study of Belgium provides insight of various parameters which should be
      taken into account for national planning of physicians. It also shows the
      difficulty to assess a complex future and the factors which often hinder the
      implementation of evidence-based decisions.

PMID- 23951855
TI  - [Management of comorbidities in heart failure].
AB  - We will review some diseases that interfere most with management of heart failure
      : anemia, chronic renal failure, chronic pulmonary diseases, diabetes, atrial
      fibrillation/flutter, sleep apnea, angina, systemic arterial hypertension,
      rheumatic disease, depression and anticancer chemotherapy. We will retain
      principally their therapeutic implications. Anemia can be partially corrected by
      administration of intravenous iron or erythropoietin. Chronic renal failure
      requires adaptation of the treatment, in particular for drugs of the renin
      angiotensin-aldosterone system. Chronic pulmonary diseases complicate diagnosis
      of heart failure and may lead to sub prescription of beta-blockers. Diabetes does
      not alter the usual recommendations for the treatment of heart failure but some
      hypoglycemic medications should be prescribed with caution. In the presence of
      atrial fibrillation or flutter, the main purpose of the treatment is to improve
      the quality of live and to diminish the thromboembolic risk ; it may be obtained
      by rhythm or rate control. Therapeutic approach of sleep apnea is based on
      optimal treatment of heart failure and weight loss. In the presence of angina,
      systemic arterial hypertension, rheumatic disease or depression, certain drugs
      usually prescribed are contraindicated or must be prescribed with caution.
      Finally, chemotherapy can be cardiotoxic and require careful monitoring of
      cardiac function.

PMID- 23951856
TI  - [Medical complications of extracorporeal lithotripsy].
AB  - Extracorporeal shock wave lithotripsy (ESWL) is one of the most frequently
      applied procedures for the treatment of urolithiasis. ESWL breaks and splits
      stones by the means of repeated acoustic shock waves. Despite its non invasive
      nature, ESWL has been intuitively associated with potential complications, mostly
      related to residual stone fragments. While non stone-related complications are
      rare (< 1 %), awareness and identification of these complications could help
      clinicians to prevent and manage them safely and effectively. The current study
      reviews the pathophysiology, predicting factors and possible preventive measures
      of non stone-related medical complications after ESWL.

PMID- 23951857
TI  - [Assessment of cardiorespiratory functional fitness in children: walking tests
      and running tests].
AB  - Cardiorespiratory fitness (CF) is an important factor in treating various
      paediatric pathologies. As a consequence, assessing CF has widespread clinical
      application as part of paediatric intervention programs. Several methods have
      been developed for the purpose of measuring CF. The aim of this review is to
      describe and evaluate test procedures that are currently in use. Direct
      measurement in a laboratory setting has the advantage of high validity and
      reliability. The disadvantage, however, is that laboratory assessment of CF
      requires trained personnel, takes more time than field tests, and necessitates
      costly equipment. Conversely, field tests are easier to administer, require less
      time and utilise less expensive equipment. The choice of the test mode must take
      into account the age and health of the subject. The availability of a variety of
      tests makes it possible for the clinician/researcher to choose the most
      assessment that is most appropriate for the target population, study objectives,
      and available resources according to the research methods of the study.

PMID- 23951858
TI  - [Pseudo-hyperkalemia and hyperleukocytosis].
AB  - A pseudo-hyperkalemia may occur with hyperleukocytosis. It is important to
      recognize it early to avoid unnecessary or even dangerous treatment inducing
      hypokalemia. The pseudohyperkalemia is due to cell fragility coupled to
      mechanical phenomena during blood collecting. We report a case of pseudo
      hyperkalemia in a context of acute myeloid leukemia.

PMID- 23951859
TI  - [An atypical presentation of bronchial adenocarcinoma].
AB  - Currently, adenocarcinoma represents 41 % of primary lung cancers in women and 34
      % in men. Thyroid metastases of lung cancer are rare and usually asymptomatic. We
      report the case of a patient presenting with stridor secondary to an enlarged
      multiple nodular thyroid accompanied by cervical lymphadenopathies accompanied by
      an enlarged and multiple nodular thyroid and by stridor. The final diagnosis was
      thyroid metastases of primary lung adenocarcinoma.

PMID- 23951860
TI  - [Pierre-Joseph-Cecilien Simonart (1816-1847) and the problem of amniotic bands].
AB  - Pierre-Joseph-Cecilien Simonart (1816-1847) was an obstetrician and an anatomist
      in the Universite libre de Bruxelles. He described and analyzed the "amniotic
      bands" and their effects on the fetus. In this contribution, we situate his work
      in the evolution of the knowledge relative to this pathology.

PMID- 23951861
TI  - [Oncogeriatrics, where are we?].

PMID- 23951862
TI  - [Surgical risk for emergency surgery in the elderly].

PMID- 23951863
TI  - [Using video games to prevent cognitive decline].

PMID- 23951864
TI  - [Deglutition disorders in elderly patients].
AB  - Deglutition disorders are frequent in elderly patients and can lead to serious
      consequences in terms of morbidity and mortality. Despite an easy screening test
      with the water, they are ignored or underestimated. Moreover, early detection and
      treatment focused essentially on the adaptation of textures, postures as well as
      the provision of information and training to all the people involved in feeding
      the elderly person require few resources and provide a real benefit.

PMID- 23951865
TI  - [Non-drug-based management of Alzheimer's disease].
AB  - Alzheimer's disease requires specific patient management. This can involve non
      drug-based treatments such as a cognitive stimulation programme to reinforce the
      patient's skills. By offering a combination of information and training to the
      family and caregivers, the patient's quality of life can be improved.

PMID- 23951866
TI  - [Taking care of the clothing of residents is preserving their dignity].

PMID- 23951867
TI  - [The case manager, a geriatrics healthcare coordinator].
AB  - The case manager mobilises the resources available within a geographic sector
      determined by the Centre for the autonomy and integration of Alzheimer's patients
      in order to respond to complex cases of elderly patient care.

PMID- 23951868
TI  - [The emergency department, a place for orientation and care].

PMID- 23951869
TI  - [Emergency medicine and the elderly].
AB  - Over the last twenty years or so, emergency departments have undergone
      significant changes. They have faced a continual increase in activity of around 2
      to 5% per year. Numerous factors are to be taken into account with regard to
      elderly people, notably their fragility. This is why a full assessment is
      essential when the patient arrives. Whenever possible, a return home must be
      favoured.

PMID- 23951870
TI  - [Elderly patients in emergency departments, the challenges of assessment on
      arrival].
AB  - The proportion of elderly patients is increasing in emergency departments. The
      assessment phase on arrival is fundamental and determines the future orientation
      of the patient.The objectives are to identify the "fragile" patient, to assess
      the pain in an adapted manner, to make the patient autonomous and to gather
      objective signs which are sometimes masked by aspecific reasons for the patient
      having been brought to the emergency department. Assessment tools and practice
      guidelines, adapted to this section of the population, exist, have been tested
      and must be generalised. Moreover, working in vertically-integrated pathways must
      be developed. It is important that the elderly patient is managed in a specific
      way in emergency departments, in the shortest time possible.

PMID- 23951871
TI  - [The geriatrics post-emergency and orientation unit].
AB  - The specific aims of a geriatrics post-emergency and orientation unit (UPUOG) are
      to provide early and global management of the patients, to preserve their
      autonomy and to anticipate the care and life project. This article presents the
      example of the University hospital of Nancy.

PMID- 23951872
TI  - [Coordination in emergency departments by a mobile geriatrics unit].
AB  - One of the missions of the Centre mobile geriatrics unit in Marseille is to
      ensure the orientation towards the most suitable medical services of elderly
      patients seen in emergency departments who require admission to hospital. This
      regulation is preceded by the collection of geriatric and gerontological clinical
      data which are transferred to the ward to which the patient is being admitted.
      The 1 039 patients assessed in 2011 were fragile, polypathological people
      requiring specific geriatric patient management.

PMID- 23951873
TI  - [The mobile geriatrics team, global patient management].
AB  - The mobile geriatric team of Cochin hospital in Paris is responsible for the
      management and orientation of fragile elderly patients over the age of 75
      admitted to emergency departments. It carries out a multi-disciplinary
      assessment, contributes to the creation of the care project and life project of
      geriatric patients and is involved in organising the patient's return home. This
      article focuses on the role of the social assistant through two clinical cases.

PMID- 23951874
TI  - [Training in emergency procedures and care and management of elderly people].
AB  - Since the introduction of skills-based training reference frameworks for the
      training of nursing assistants and student nurses, certification in training in
      emergency procedures and care is an integral part of the initial training of
      future healthcare professionals. The elderly person is a great example for
      learning rightgestures.

PMID- 23951875
TI  - [Bibliography. Emergency services for the elderly].

PMID- 23951876
TI  - [Resenting patient isolation].

PMID- 23951877
TI  - [Medication errors in the elderly patient].

PMID- 23951878
TI  - [Necessary to strengthen care and research on mental illness].

PMID- 23951879
TI  - [HIV/AIDS, tuberculosis and malaria can now be effectively combated].

PMID- 23951880
TI  - [TEG and ROTEM--bedside and rapid coagulation assays. Reduces the need for
      transfusion during liver and heart surgery, but questions remain].

PMID- 23951881
TI  - [Pulmonary tularemia: rare disease that can be interpreted as lung cancer.
      Serology provides the correct diagnosis, as shown by case reports].

PMID- 23951882
TI  - [Very varied prescription of antibiotics in primary care. Low adherence to
      guidelines in throat infections, as shown by diagnosis based data].

PMID- 23951883
TI  - [Cardiac myxomas may debut as TIA or stroke. Echocardiography provides tumor
      diagnosis].

PMID- 23951884
TI  - [ICF is a good tool to describe activity limitations in sick leave. General
      practitioners and the Swedish Social Insurance Agency are positive, as shown by
      qualitative study].

PMID- 23951886
TI  - [Pascal turns one--time for the next step].

PMID- 23951885
TI  - [Reflective writing and personal conversation in the medical education. New
      elements in a psychology course contributed to increased self-awareness].

PMID- 23951887
TI  - [Acknowledge patients rights to online medical records].

PMID- 23951888
TI  - [A question of ethics and flexibility].

PMID- 23951889
TI  - ["HEART score"--the solution for secure management of patients with suspected
      acute coronary syndrome in the emergency department?].

PMID- 23951890
TI  - [Supporting roles in Swedish elderly care].

PMID- 23951891
TI  - [Modern aspects of the prevention of diseases of the digestive system in children
      ].
AB  - The article reviews the modern aspects of the prevention of diseases of the
      digestive system in children. It analyzes the levels of prevention activities,
      starting with the first days of a child's life. Great value is given to healthy
      ways of parents' lives, in the future - of the children: monitoring the course of
      pregnancy, genetic counseling and prenatal diagnostics of the pathology of the
      fetus. Heredity plays an important role in the cause-significant factors of
      diseases of the digestive system, violations of the calendar of vaccination, etc.
      One of the bases of prevention is a staged treatment of diseases of the digestive
      system, the identification of risk factors that can cause an aggravation or a
      continuously-recurrent course. The selection of rehabilitation programmes and
      hospital replacement technologies to improve and maintain the quality of life of
      sick children were substantiated.

PMID- 23951892
TI  - [Mediko-social aspects of ecological gastroenterology].
AB  - Are investigated infringements of indicators antioxigion organism protection at
      hectare-stroenterology diseases at the patients living in territory of
      Krasnodarsky edge with various levels of pollution of an inhabitancy by
      pesticides and heavy metals. The ecological concept of an aetiology form chronic
      inflammatory diseases of bodies of digestive system which assumes the mechanism
      of decrease in resistance of an organism, development nonspetial the processes
      conducting to chronisation and complication of a current of diseases is
      considered.

PMID- 23951893
TI  - [Clinical and pathogenetic significance of collagen metabolism disorder in
      children with gastroesophageal reflux disease].
AB  - In 62 children with gastroesophageal reflux disease (GERD) and 32 with
      gastroduodenitis (DG) aged 9-17 years, the peculiarities of metabolism of
      collagen were studied. High levels of fractions of sialic acids were set, that
      was associated with the protein fructose, fractions of hydroxyproline in children
      with GERD compared with the patients with DG, which testify to the process of
      degradation of collagen and may be one of the factors contributing to the local
      inflammation of the esophagus and gastroduodenal zone of the digestive tract. The
      prevalence of Helicobacter pylori, as well as violations of diet, play an
      important role in maintaining the inflammatory process.

PMID- 23951894
TI  - [Acid resistance of erythrocytes in children with chronic inflammatory diseases
      of the stomach and duodenum during the course of the hyperbaric oxygenation].
AB  - The use of additional methods of treatment of ulcers of the duodenum determines
      necessity of development of methods of evaluation and control of the efficiency
      of the treatment. With the help of the method of acid erhytrogrammes highlighted
      the most significant signs of describing the change in erythrocyte membranes of
      children with duodenal ulcer disease during the course of the hyperbaric
      oxygenation.

PMID- 23951895
TI  - [The natural course of chronic HBV+HCV infection in children].
AB  - At the present time there is a growth in the number of children suffering from
      chronic viral hepatitis (CVH). The most difficult group consists of patients with
      mixed-hepatitis, which is associated with a more rapid progression of the disease
      and the formation of cirrhosis of the liver. The paper presents the data of long
      term monitoring of children with chronic hepatitis B+C (CH B+C); it demonstrates
      the features of a clinical course, the nature of the biochemical, immunologic,
      and morphologic changes in the natural course of the disease.

PMID- 23951896
TI  - [Peculiarities of functional status and microbiocenosis of the intestines in
      children with metabolic syndrome].
AB  - The article is devoted to the study of the functional state and microbiocenosis
      of intestines in children with a metabolic syndrome based on the study of the
      qualitative and quantitative composition of short-chain fatty acids in feces and
      blood serum. The results of the study showed that children with MS have a high
      rate of registered functional disorders of the intestine, characterized by the
      change of the nature of the chair and the results of scatological and biochemical
      tests. Disbiotic violations, accompanied by a reduction in the number and the
      metabolic activity of the indigenous microflora, change in the activity of
      anaerobic microorganisms were identified, which manifests itself as
      characteristic changes of qualitative and quantitative composition of the SHQ in
      the feces and blood serum.

PMID- 23951897
TI  - [Viral and drug-induced liver damage in children with tuberculosis: prevalence,
      clinical features].
AB  - THE AIM OF THE RESEARCH: Improving the effectiveness of diagnostics and treatment
      of viral and drug-induced lesions of the liver (DILL) at a tuberculosis in
      children by identifying the frequency of their distribution, peculiarities of
      diagnostics and clinics. MATERIALS AND METHODS: We examined 242 children in the
      age from 2 months to 17 years, the patients with different forms of tuberculosis.
      RESULTS: The prevalence of hepatitis in children with tuberculosis: B - 1,2%, C
      0.4%, G - 4,6%, TT - 8,7%. DILL was diagnosed in 67.5% of children - TB patients,
      in 48% of the children with DILL an asymptomatic course of the disease was noted,
      however, in 54.4% of the children with DILL cytolitic syndrome was expressed
      (ALT> standards). CONCLUSION: The prevalence of viral hepatitis B and C among
      children with TB is low. The infection with viruses of hepatitis G and TT is more
      often, but has no significant impact as on the course of tuberculosis, and on the
      severity of the liver damage. Drug-induced liver damage is a dominant view of
      pathology of the liver in children - TB patients and is mostly asymptomatic, but
      with a pronounced cytolitic syndrome.

PMID- 23951898
TI  - [The evaluation of clinical effectiveness of the treatment of autonomic system
      disorders in children with hepatobiliary pathology living in conditions of
      anthropogenic environments].

PMID- 23951899
TI  - [Risk factors and mechanisms of the postcholecystectomy syndrome development in
      children].
AB  - Cholelithiasis has long ceased to be casuistry in childhood. In connection with
      the steady tendency for it to grow, it has increased the number of surgical
      interventions on the occasion of holelitiazis. The removal of the gall bladder in
      some patients is accompanied by disorders on the part of the digestive system,
      identified as postcholecystectomical syndrome. The article describes the risk
      factors and mechanisms of the formation of the postcholecystectomical syndrome in
      children.

PMID- 23951900
TI  - [Anthropometric measures of children in the period of clinical manifestation of
      celiac disease].
AB  - We have analyzed the data of children's physical development who have celiac
      disease. The purpose of the study is to analyze the interrelations of celiac
      patients' anthropometric data with the age of diagnostics and the disease
      duration. 186 children with morphologically verified celiac disease at the age of
      from 9 months to 16 years were included. It was shown that the patients of pre
      preschool age have the deficiency of body weight much more often than the growth
      delay. As they grow older and when the disease duration increases first of all we
      meet with stunting, as the result a number of children with normal growth at
      school age decreases to 23, 3 %, and the frequency of somatogenic nanism exceeds
      50%. We have revealed the negative correlation between the symptoms duration of
      the disease and the deviation of growth data. We have confirmed the point of view
      that the presence of strong deviations of data of physical development which
      children have is the indication for the screening for celiac disease.

PMID- 23951901
TI  - [Defects of neutrophil function in chronic gastroduodenitis in children].
AB  - At present, chronic gastroduodenitis (CGD) occupies one ofthe leading places in
      the structure of diseases of the gastrointestinal tract in children. In the
      etiology of CGD, along with the leading pathogenic Helicobacterpylori (HP), the
      role of the fungal flora increased. The aim of the work was to evaluate the
      functional activity of neutrophils in children with the CGD, associated with HP
      and Candida albicans. Among 110 children in the age from 7 to 17 years with
      chronic gastroduodenitis, associated with Helicobacter pylory(HP), as well as the
      association of HP with Candida albicans and the markers of secondary immune
      insufficiency, a study of the phagocytic activity and immune phenotype of
      neutrophils by flow cytofluorimetry was conducted. Differentiated peculiarities
      of the phagocytic activity of neutrophils in association with bacterial pathogens
      (HP) and fungal flora were identified. The transformation of the immune phenotype
      was combined with a significant depression of the phagocytic and microbicidal
      functions, more pronounced with the association of HP and Candida albicans.
      Circulating mannano protein antigen of Candida albicans influenced on the surface
      of phenotype of neutrophils, increasing the expression of protopathic and HLADR
      receptors, and decreasing the expression of adhesion receptors and cytolysis.
      Thus, in case of chronic gastroduodenitis in children, there was a considerable
      transformation of the phenotype of neutrophil with differentiated characteristics
      at the association with bacterial (HP) pathogens and fungal flora. The obtained
      data should be taken into account when carrying out medical activities, and the
      doctors should include in the composition of complex therapy of CGD, associated
      with Candida albicans, drugs, aimed at immunocorrection of the identified
      violations

PMID- 23951902
TI  - [Postcholecystectomy syndrome in children (case report)].
AB  - The article presents the case of the development of the postcholecystectomical
      syndrome in a child with a gallstone disease after cholecystectomy. It describes
      the clinical picture of the postcholecystectomical syndrome, identifies
      laboratory changes, characteristic for the postcholecystectomical syndrome in
      children. The aim of this work was to show the clinical example of the difficulty
      of detecting signs of the postcholecystectomical syndrome in children for the
      optimization of the diagnostic tactics.

PMID- 23951903
TI  - [The metabolic syndrome in children: resolved and unresolved questions of
      ethiopathogenesis (review of literature)].
AB  - The article raises the question of modern views on pathogenesis and algorithms
      for the diagnosis of metabolic syndrome in children. It shows the close
      relationship of violations of the morphofunctional state of the hepatobiliary
      system and pancreas with the development of hormonal-metabolic disorders.

PMID- 23951905
TI  - [The modern condition of pediatric gastroenterology in America].

PMID- 23951904
TI  - [Probiotic strains of enterococci as a means of therapy and prophylaxis of
      intestinal diseases in children (review of literature)].
AB  - Probiotic enterococci a widely used by pediatricians and infection diseases
      doctors in Russia as means for the treatment of dysbiosis, irritated bowel
      syndrome and in the treatment and prevention of different functional and chronic
      intestinal diseases. Strains E. faecium M74 and E. faecium SF-68 are included in
      several probiotic drugs and have been proved as effective and safe. Several
      studies suggest that the usage of Russian probiotic strain E. faecium L3 in
      pediatrics is promising. The review is devoted to the analysis of clinical
      studies in pediatric practice employing probiotic enterococci.

PMID- 23951906
TI  - [Nanobiophotonics: photon-associated nanobiotechnology for laser and personalized
      medicine].
AB  - Analyzed are the literature in the field of development and use nanobiophotonic
      technologies for laser and personalized medicine. Arguably, the origins of
      nanobiophotonic are closely tied in the first experimental realization of near
      field optics, which enabled optical imaging beyond the diffraction limit. The
      information about the gist of nanobiophotonics and other photon-associations
      technologies (photonics, nanophotonics, biophotonics, nanooptics, plasmonics,
      nanospectroscopy, laser and personalized medicine) is summarized.
      Nanobiophotonics is the use of light to image, probe and manipulate biological
      materials. The particular strength of nanobiophotonics is thet in ideal case it
      retains of the light for permits live cell sensing. The area of nanobiophotonics
      technologies is too broad to possible capture all aspects nano-analitic
      directions and biomedical research within the last years.

PMID- 23951907
TI  - [Quantum-pharmacological aspects of cardiovascular drugs studying].
AB  - Quantum pharmacology allows to study the mechanisms of action of cardiovascular
      drugs, to predict pharmacological activity and identify the most pronounced
      pharmacodynamic efficacy and therapeutic activity of new compounds. Calculation
      of quantum-pharmacological parameters for molecules of beta-blockers
      (propranolol, atenolol, metoprolol, carvedilol) in aqueous media, research its
      hydrophobic interaction with receptors allow to form a theoretical basis for the
      development of new generations of more effective and safe medicines for
      hypertension treatment. Increased hydrophobicity leads to poor solubility of
      carvedilol in water and high--in the lipids. The clinical pharmacology of the
      drug is shown by such indicators as the therapeutic dose, half-life and degree of
      metabolism in the liver. Due to enhanced interaction with adrenergic receptor
      effective dose of carvedilol is an order of magnitude lower than other beta
      blockers, even with the relatively low bioavailability. Reduced bioavailability
      of carvedilol versus atenolol, metoprolol and propranolol is caused by elevated
      metabolism during the first pass through the liver, which is also due to the
      hydrophobicity of the drug. High solubility in lipids appears to extend the half
      life of carvedilol. QSAR studies make an important contribution to the study of
      the properties of chemical compounds and their pharmacological activity.
      Software, used for computation of studied properties, has a significant role. A
      large number of descriptors allows a qualitative and quantitative assessment of
      the molecules of chemical compounds and prediction of their influence on
      cardiovascular system.

PMID- 23951908
TI  - [About etiology and pathogenesis of atherosclerosis].
AB  - On the ground own researches and researches of other authors etiology and
      pathogenesis of atherosclerosis are proved and refuted existing concept about
      leading role of disturbance of lipid exchange and atherogenicity of lipoproteins
      of low and very low density. Established basic etiological factors of damage
      intima of artery and reason of penetration of lipoproteins in intima after her
      damage. Is determined that development and progression of atherosclerosis do not
      depend also from quantitative content of lipoproteins of low density in blood and
      from normalization of them under influence of drugs. According to our researches
      atherosclerosis is the polyetiological chronic disease basis of pathogeny which
      is infringement of blood supply (chronic microcirculatory insufficiency) in
      arterial wall causing damage of it, and in first place, damage of intima with her
      most vulnerable microcirculation; inflammation intima hence influence of
      endogenous and exogenous factors; destruction of antiaggregatic and fibrinolytic
      properties of intima in places of her damage; formation atherosclerotic plaque
      with level-by-level imposing of lipoproteins in result of cyclic process of
      restoration or balance between coagulation and anticoagulation of blood systems.

PMID- 23951909
TI  - [Postprandial hypotension].
AB  - Postprandial hypotension is the independent risk factor of general mortality,
      coronary disorders and stroke. It is reviewed risk factors, pathogenesis,
      symptoms, treatment and prognosis of this disease.

PMID- 23951910
TI  - [Syndrome "sickly child"].
AB  - Scientific review is devoted to the urgent problem of child health care--Syndrome
      "sickly child" described in detail the category of "frequently ill children"
      repeated respiratory diseases, the pathogens that cause diseases of the
      respiratory tract. Paying attention to factors contributing to re-respiratory
      morbidity, including genetically determined causes (disturbances in the state of
      health of the mother), is represented by the genetic determinism of repeated and
      recurrent diseases related to blood groups. The development of an immune
      imbalance is manifested by changes in the cellular, humoral immune response and
      nonspecific resistance factors characterizing the changes of local immunity in
      this category of children that shape the development of chronic disease. We
      describe the effect of an allergic component to the severity of respiratory
      disease and the relationship with the mechanisms of neuroendocrine and immune
      systems. Correction of the immune resistance of sickly children was conducted
      cycloferon contributing to reduce the incidence and duration of repeated episodes
      of acute respiratory infections per year.

PMID- 23951911
TI  - [Characteristics of proatherogenic disorder development in women with different
      reproductive status].
AB  - The occurrence and structure of dyslipidemias, the result of the concentration of
      C-reactive protein in blood serum and some results of hormonal background in
      women with cardialgias in reproductive age, during peri- and postmenopause were
      studied. The features of proatherogenic disorders connected with dominating types
      of dyslipidemias, the degree of chronic inflammation manifestation and some
      results of hormonal background were established for people with certain
      reproductive status.

PMID- 23951912
TI  - [Prevalence of small anomalies of the heart development in preterm born
      children].
AB  - The purpose of work was an assessment heart small anomalies prevalence at
      children that was born as late-pretrem. By echocardiography method the 93
      children at the age of 10-12 years were investigated. Frequency of detection
      heart small anomalies was 59% and at children with disproportional development at
      the birth--77%. Prevailing anomalies of development were anomalies of the left
      side of the heart, the mainly left ventricle abnormally located chords.

PMID- 23951913
TI  - [Biomarkers and risk factors of cardiovascular system disease in diabetes
      mellitus type 2].
AB  - The content of glycated hemoglobin, a biomarker of diabetes in patients with type
      2 diabetes correlates with risk factors for cardiovascular disease: hypertension,
      BMI and ratio of total cholesterol to HDL cholesterol. Therefore, increase in
      glycosylated hemoglobin should be considered a predictor of cardiovascular
      disease in patients with type 2 diabetes.

PMID- 23951914
TI  - [Neurological characteristics of the ischemic stroke course in patients with
      atrial fibrillation].
AB  - The article contains the results of investigation on particularities of the
      ischemic stroke course in patients with atrial fibrillation. Neurological
      particularities of the ischemic stroke course in patients with atrial
      fibrillation are characterized with disorders of central hemodynamics, worse
      neurological status, high mortality. Neuroimaging features of ischemic stroke in
      patients with atrial fibrillation are similar to those in group without
      arrhythmia (P > 0.05). Ischemic focus is more frequently localized in left
      cerebral medium artery in all patients. Significant difference in the level of
      mean systolic and diastolic blood pressure between groups has not been detected
      (P > 0.05). The majority of patients with cardioembolic stroke had permanent
      atrial fibrillation (86.4%).

PMID- 23951915
TI  - [Duplex scanning of the changes in the vertebral arteries in patients with
      ischemic stroke in the vertebro-basilar basin].
AB  - With duplex scanning of neck vessels in 120 patients with acute ischemic stroke
      in the vertebrobasilar basin revealed changes in the vertebral artery in (68.3%)
      of patients, which cause difficulty in blood flow in the vessels of vertebro
      basilar basin. Among them were seen often atherosclerotic stenoses (53.3%),
      deformation (11.7%) and abnormal discharge of vertebral arteries (3.3%).

PMID- 23951916
TI  - [Qualitative analysis of accented CD158a receptor expression in NK-lymphocytes in
      women with reproductive failures].
AB  - Blood from 91 women that undergoing IVF cycle was analysed for NK cells CD158a
      expression using a monoclonal antibody and FACScan flow cytometer and CellQuest
      software (BD Bioscience, San Jose, USA). Patients were separated on 3 groups
      according implantation and pregnancy results in actual IVF cycle. 53 patients not
      became pregnant (IVF failure group F), 24 became pregnant after IVF with
      subsequent successful pregnancy (Pregnancy succes group PS) and 13 became
      pregnant with subsequently pregnancy failure (Pregnancy failure group PF).
      Average levels of of CD158a on NK cells were significant increase in patients
      that not became pregnant compared to pregnant group. However IVF failure patients
      have comparable average CD158a levels to reproductive success group. Patients
      with pregnancy failure have significant decreased CD158a levels compared to both
      IVF failure and reproduct success patients. A qualitative analysis of NK CD158a
      expression showed that 22/24 (92.8%) women who became pregnant and live birth had
      CD158a levels that were > 20 but < 65%. In contrast only 62.8% patients form IVF
      failure and 61.6% from Pregnancy failure group had CD158a expression on NK in
      this zones (corridor). 38.4% of patients from pregnancy failure group had CD158a
      expression levels lower than 20% and as a result significant decreased average
      value in whole group. In contrast IVF failure patients had increased CD158a
      expression in 9.5% cases and decreased in 27.7% and as a result similar average
      levels to pregnancy success groups. Decreased CD158a expression (< 20%) was
      significant predictive factor for reproductive failure (OR 10,7) Increased CD158a
      expression > 65%) was predictive factor for Implantation failure (OR 5,4; P =
      0,09) Normal CD158a expression (> 20% but < 65%) was significant predictive for
      IVF implantation and Pregnancy success and as a result for common Reproduct
      success (OR 2,7; 6,87; 6,92). We found that normal NK CD158a expression is
      associated with successful IVF and pregnancy. Preference of qualitative analysis
      under simple average value comparison in case of bilateral distribution of
      parameters was shown.

PMID- 23951917
TI  - [Laparoscopy in the treatment of complicated forms of acute cholecystitis].
AB  - The results of treatment 157 patients 19-88 years with complicated forms of acute
      cholecystitis. In the first stage 34 patients with destructive cholecystitis and
      obstructive jaundice, and 4 patients with pancreatitis underwent endoscopic
      retrograde cholangiopancreatography, and papillosphincterotomy litoekstraktsiya.
      In 33 cases, percutaneous transhepatic drainage is carried out of the
      gallbladder. All patients were operated laparoscopically. In 34 observations
      during the operation was found loose in the 37 observations--dense perivesical
      infiltration. The conclusion about the priority of minimally invasive
      interventions in complicated forms of cholelithiasis and acute cholecystitis.

PMID- 23951918
TI  - [Characteristics of group psycho-prevention and psycho-correction of beer
      dependence in teenagers].
AB  - The article is devoted community principles and stages of the psychoprevental and
      correctional approach for teenagers with beer.

PMID- 23951919
TI  - [Efficiency of modern technology in obstetric practice].
AB  - Bleeding is one of the key components of critical states in obstetrics. The fight
      against obstetric hemorrhage related to the following aspects: the organization
      of care, qualifications of medical personnel, the availability and quality of the
      protocol. The introduction of modern technologies to reduce the frequency of
      massive postpartum hemorrhage and disability among women of reproductive age.

PMID- 23951920
TI  - [The complex rehabilitation treatment of patients with chronic obstructive
      pulmonary disease using haloaerosoltherapy and blastomunil (remote results)].
AB  - The expediency of complex recovery treatment of chronic obstructive pulmonary
      disease patients with the usage of artificial rock salt aerosol medium
      (haloaerosoltherapy) and immunomodulator "Blastomunil" intake was grounded on the
      base of the treatment's remote results study. It was revealed that additional
      prescription of blastomunil resulted in the lowering the frequency of ambulant
      and, especially, hospital treatment, decrease of average quantity of disability
      days during one year after treatment and promoted the remission lengthening by
      1,9-2,1 months.

PMID- 23951921
TI  - [Clinical effectiveness of metformin and ramipril combination in complex therapy
      of patients with metabolic syndrome].
AB  - 6 monthly application of the combination of metformin with ramipril (1000 and 5
      mg per day respectively) in complex treatment of metabolic syndrome (MS) leads to
      improvement of the clinical course of ischemic heart disease (decrease of
      quantity and duration of painful cardial attacks, depression of the functional
      class of an angina of exertion, decrease of displays of chronic heart failure),
      normalization of arterial pressure and decrease of an abdominal obesity which can
      be considered as prophylaxis of development of diabetes mellitus 2 types and its
      cardiovascular complications. Combination of metformin with ramipril in complex
      treatment of a MS is effective and safe option of therapy of MS.

PMID- 23951922
TI  - [Dynamics of emotional changes during education of foreign and domestic students
      in sports specialties].
AB  - This article presents the results of a comparative analysis of the dynamics of
      the well-being of foreign and domestic students sporting disciplines defined by
      studying the performance of their emotional state at different stages of the
      learning process. It was found that the decrease in value of the conditional
      measures of psychological atmosphere of the day, as the main indicator of the
      emotional state of students is more pronounced in the group of foreign students.
      The reason for this phenomenon is a chronic emotional stress caused by the
      conflict between the desire of students to the successful development of training
      programs and the inability to effectively receive educational material due the
      insufficient knowledge of the terms of professional and applied value. One way of
      solving this problem is the use of the method of accelerated expansion of
      vocabulary terms of professional and practical importance in the program of
      preparation of foreign students to study in the higher educational institutions
      of Ukraine.

PMID- 23951923
TI  - [Activity of some enzymes in peripheral blood erythrocytes in sportsmen].
AB  - It is determined that physical exercises in sportsmen-runners at medium distances
      cause changes of glucose-6-phosphate dehydrogenase, lactate dehydrogenase and its
      fractions activity in peripheral blood erythrocytes. The maximal changes are
      observed after competitions.

PMID- 23951924
TI  - [The life and scientific work of outstanding Ukrainian obstetrician-gynecologist
      Grygorii Fedorovych Pisemskyi (to 150th birthday anniversary)].
AB  - Thy article presents data about well-known Ukrainian physician, obstetrician
      gynecologist, scientist, organizer, teacher prof. G. F. Pisemsky, his role in the
      development of Obstetrics and Gynecology.

PMID- 23951925
TI  - The complete mitochondrial genome of Pallisentis celatus (Acanthocephala) with
      phylogenetic analysis of acanthocephalans and rotifers.
AB  - Acanthocephalans are a small group of obligate endoparasites. They and rotifers
      are recently placed in a group called Syndermata. However, phylogenetic
      relationships within classes of acanthocephalans, and between them and rotifers,
      have not been well resolved, possibly due to the lack of molecular data suitable
      for such analysis. In this study, the mitochondrial (mt) genome was sequenced
      from Pallisentis celatus (Van Cleave, 1928), an acanthocephalan in the class
      Eoacanthocephala, an intestinal parasite of rice-field eel, Monopterus albus
      (Zuiew, 1793), in China. The complete mt genome sequence of P. celatus is 13 855
      bp long, containing 36 genes including 12 protein-coding genes, 22 transfer RNAs
      (tRNAs) and 2 ribosomal RNAs (rRNAs) as reported for other acanthocephalan
      species. All genes are encoded on the same strand and in the same direction.
      Phylogenetic analysis indicated that acanthocephalans are closely related with a
      clade containing bdelloids, which then correlates with the clade containing
      monogononts. The class Eoacanthocephala, containing P. celatus and
      Paratenuisentis ambiguus (Van Cleave, 1921) was closely related to the
      Palaeacanthocephala. It is thus indicated that acanthocephalans may be just
      clustered among groups of rotifers. However, the resolving of phylogenetic
      relationship among all classes of acanthocephalans and between them and rotifers
      may require further sampling and more molecular data.

PMID- 23951926
TI  - A review of picobiine mites (Acari: Syringophilidae: Picobiinae) parasitising
      African birds.
AB  - A fauna of quill mites of the subfamily Picobiinae (Acari: Syringophilidae)
      associated with African birds is revised. Two new monotypic genera are proposed,
      Gunabopicobia gen. n. for Picobia zumpti Lawrence, 1959 and Lawrencipicobia gen.
      n. for Picobia poicephali Skoracki et Dabert, 2002. These new genera differ from
      other genera of the subfamily by the following features: in females of
      Gunabopicobia, propodonotal setae vi are situated anterior to the level of setae
      ve; the narrow lateral propodonotal shields bear bases of setae vi, ve, si and
      se; the bases of setae 1a-1a are coalesced; the genital setae and the
      opisthosomal lobes are absent; the leg I with full set of solenidia and apodemes
      I are devoid of the thorn-like protuberances in the middle part. In females of
      Lawrencipicobia, the bases of setae 1a-1a are not coalesced; the propodonotal
      shield is entire; the genital setae are present; legs I are with full set of
      solenidia. Additionally, two new species belonging to Picobia Haller, 1878 are
      described, Picobia illadopsae sp. n. parasitising Illadopsis rufipennis (Sharpe)
      (Passeriformes: Pellorneidae) in Kenya and Picobia phoenicuri sp. n. infecting
      Phoenicurus moussieri (Olphe-Galliard) in Tunisia. The following species are
      redescribed, Columbiphilus alectoris (Fain, Bochkov et Mironov, 2000),
      Lawrencipicobia poicephali (Skoracki et Dabert, 2001) comb. n. and Picobia
      phoeniculi (Fain, Bochkov et Mironov, 2000). The key to the genera of the
      Picobiinae is provided.

PMID- 23951927
TI  - The expression of malarial invasion-related molecules is affected by two
      different nitric oxide-based treatments.
AB  - The host immune response to parasitic infections plays an important role in
      controlling multiplication of the parasite and reducing clinical symptoms and
      life-threatening complications. Nitric oxide (NO), an important innate immune
      factor and classic Th1 immune effector, may play a role in inhibiting plasmodium
      infection. In this study, we used two different approaches (L-Arginine [precursor
      of NO] and NOC5 [short-time NO donor]) to prove the roles of NO in malaria
      infection. We used 6-8 week-old female BALB/c mice infected with the rodent
      malaria Plasmodium yoelii Landau, Michel et Adam, 1968 - strain 17XL (P.y17XL) as
      a model. For L-Arg treatment, mice were administered with an oral dose of 1.5
      mg/g L-Arg daily for seven consecutive days prior to infection with Py17XL. L-Arg
      pretreatment resulted in the decrease of the mRNA level of the apical membrane
      antigen 1 (AMA1) gene, which encodes a protein involved in host invasion. For
      NOC5 treatment, NOC5 was injected intraperitoneally into the P.y17XL infected
      mice on day 5 post-infection or incubated in vitro with purified Py17XL
      schizonts. Both in vivo and in vitro treatments with NOC5 led to down-regulation
      of the transcript and protein levels of invasion-related molecules (AMA1,
      merozoites surface protein 1 and Py235). Our results confirmed the protective
      role of NO in the asexual blood stage of parasitic infection, which may be
      partially due to reduced expression of parasite invasion molecules.

PMID- 23951928
TI  - Molecular characterization of Leishmania spp. in reservoir hosts in endemic foci
      of zoonotic cutaneous leishmaniasis in Iran.
AB  - Zoonotic cutaneous leishmaniasis (ZCL) is an expanding disease and a public
      health issue in Iran. In the present study, rate of natural infection of rodent
      populations with Leishmania was investigated in six endemic foci including 28
      villages in Golestan, Esfahan, Yazd, Fars, Khuzestan and Ilam provinces. A total
      of 593 rodents were captured and identified as Rhombomys opimus (n = 325),
      Meriones libycus (n = 171), Meriones persicus (n = 27), Tatera indica (n = 37),
      Nesokia indica (n = 12), Rattus rattus (n = 13) and Mus musculus (n = 8).
      Microscopic examinations of Giemsa-stained smears showed that 108 out of 593
      (18.2%) rodents were infected with Leishmania spp., whereas infection of 186 out
      of 593 (31.4%) rodents with Leishmania was then confirmed by ITS1-PCR. The
      highest rate of infection was found in R. opimus (prevalence of 35%) and M.
      libycus (31%). Based on Restriction Fragment Length Polymorphism (RFLP), 145
      (78%) of 186 samples detected as Leishmania DNA were identified as L. major, 8
      (4%) samples as L. turanica and 33 (18%) as mixed infection (L. major and L.
      turanica). Samples from infected rodents were inoculated subcutaneously at tail
      base of BALB/c mice. In 35 of them, nodules and ulcers containing amastigotes
      appeared at the inoculation site. The samples prepared from infected rodents were
      cultured in NNN medium and only two samples werepositive. Rhombomys opimus, M.
      libycus, M. persicus, T. indica and N. indica were confirmed as reservoir hosts
      of ZCL in the studied regions. Leishmania major infection was usually accompanied
      L. turanica in naturally infected gerbils (R. opimus and M. libycus) in Golestan,
      Esfahan and Fars provinces.

PMID- 23951929
TI  - Plasmodium, Saurocytozoon and Haemocystidium parasites (Apicomplexa:
      Plasmodiidae) from the rock agama, Laudakia caucasia (Sauria: Agamidae), in
      southern Asia.
AB  - The rock agama, Laudakia caucasia Eichwald (Agamidae) is host to Plasmodium
      caucasica sp. n. and Saurocytozoon agamidorum sp. n. in western Pakistan.
      Plasmodium caucasica is characterized by very large meronts, 11-21 by 8-17 microm
      that produce 32-67 merozoites, which nearly fill the host erythrocyte, and
      smaller, ovoid to elongate gametocytes, 6-14 by 2.5-6 microm, with length by
      width (LW) 21-55 microm2, and L/W ratio 1.0-4.0. Host cells are usually mature
      erythrocytes. In Azerbaijan, P. caucasica parasitizes immature erythroid cells.
      Dimensions of meronts are 10-16 by 6-12 microm, and merozoite numbers are 12-44.
      Gametocytes are 6-14 by 3-6 microm, with LW 31-56 microm2, and L/W ratio 1.0-4.0.
      Saurocytozoon agamidorum sp. n. gametocytes are 6.5-13 microm in diameter, with
      LW 35-79 microm2, and L/W ratio 1.0-2.2. They occupy lymphocytes as host cells,
      which are greatly distorted by gametocyte presence and often show nuclei nearly
      divided into two portions, one portion at each end of the cell. Haemocystidium
      grahami (Shortt, 1922), redescribed from material found in L. caucasia from
      Azerbaijan, has rounded to elongate gametocytes, 8-19.5 by 4-8 microm, LW 60.5
      102 microm2, and L/W ratio 1.0-4.5. The prominent light golden pigment granules
      often coalesce to nearly cover the surface of the gametocyte. The presence of P.
      caucasica and S. agamidorum extends the range of the two genera in saurian hosts
      throughout much of the southern Asia mainland.

PMID- 23951930
TI  - A new species of Choleoeimeria (Apicomplexa: Eimeriidae) from the lizard, Scincus
      hemprichii (Sauria: Scincidae).
AB  - Four out of twenty (20%) specimens of the lizard Scincus hemprichii Wiegmann,
      collected in Saudi Arabia were infected with a previously undescribed species of
      Choleoeimeria. Oocysts of Choleoeimeria jazanensis sp. n. are cylindroidal, 26 x
      15 microm, with a smooth bilayered wall and a shape index of 1.7. Oocyst residuum
      and micropyle are absent. Sporocysts are subspherical, 10 x 7 microm, with a
      shape index of 1.3. The Stieda body is absent. Sporozoites are banana-shaped, 10
      x 3 microm, with one refractile body and enclosed the fine granulated sporocyst
      residuum. The endogenous development is confined to the gall bladder epithelium,
      with infected cells being displaced from the epithelium layer towards lumen.
      Mature meronts are subspherical and estimates to produce 9-12 merozoites.
      Microgamonts are spherical in shape with diameter of 13 microm. Macrogamonts are
      subspherical with a prominent nucleus in centre and wall-forming bodies at
      periphery.

PMID- 23951931
TI  - Blood flukes (Digenea: Aporocotylidae) of walking catfishes (Siluriformes:
      Clariidae): new genus and species from the Mekong River (Vietnam) with comments
      on related catfish aporocotylids.
AB  - Nomasanguinicola canthoensis gen. et sp. n. infects the branchial vessels of
      bighead catfish, Clarias macrocephalus Gunther (Siluriformes: Clariidae), in the
      Mekong River near Can Tho, southern Vietnam. Nomasanguinicola differs from all
      other genera of fish blood flukes (Digenea: Aporocotylidae) by the combination of
      lacking body spines and by having an anterior sucker with two flanking columns of
      large denticles, an intestine comprising several short papilla-like caeca, an
      inverse U-shaped uterus, and an ootype located near the separate genital pores.
      The new species has an ootype that is posterior to the level of the female
      genital pore. That feature most easily differentiates it from the only other
      putative aporocotylid species having an anterior sucker with two flanking columns
      of large denticles, Plehniella dentata Paperna, 1964 and Sanguinicola clarias
      Imam, Marzouk, Hassan et Itman, 1984, which have an ootype that is lateral (P.
      dentata) or anterior (S. clarias) to the level of the female genital pore. These
      two species apparently lack extant type materials, infect North African catfish,
      Clarias gariepinus (Burchell), and herein are considered incertae sedis, but
      likely comprise species of Nomasanguinicola. An updated list of hosts, sites of
      infection and geographic localities for the six species and three genera of blood
      flukes that mature in catfishes is provided. The new species is the first fish
      blood fluke recorded from Vietnam and only the third reported from a walking
      catfish (Clariidae).

PMID- 23951932
TI  - A new genus and species of the Monticelliinae (Eucestoda: Proteocephalidea), a
      parasite of Pseudoplatystoma fasciatum (Pisces: Siluriformes) from the Parana
      River basin (Argentina), with comments on microtriches of proteocephalideans.
AB  - This paper describes Regoella brevis gen. n. et. sp. n. (Proteocephalidea:
      Monticelliinae), a parasite of the intestine of the barred sorubim
      Pseudoplatystoma fasciatum (Linnaeus) from the Parana River basin. The new genus
      is placed in the Monticelliinae because of the cortical position of the genital
      organs. It differs from all known genera included in the Monticelliinae by the
      following combination of characters: 1) a quadrangular scolex with a truncated
      conical apex and formed by four lobes separated by grooves; 2) uniloculate
      suckers of inverted triangular shape possessing a small cone-shaped projection at
      each corner of the anterior margin; 3) strobila consisting of a low number of
      proglottides; 4) testes arranged in one dorsal field; 5) a cirrus-sac, which
      represents more than one half of the proglottis width, cirrus surrounded by
      conspicuous chromophilic gland cells; 6) a butterfly-shaped and strongly lobulate
      ovary; and 7) formation of uterus of type 2. The examination of the tegument
      surface with scanning electron microscopy revealed the occurrence of three types
      of microtriches: acicular and capilliform filitriches and gladiate spinitriches.
      The new species is the eighth proteocephalidean reported from P. fasciatum, six
      of which are commonly found in the Amazon and Parana River basins.

PMID- 23951933
TI  - Prochristianella mattisi sp. n. (Trypanorhyncha: Eutetrarhynchidae) from the
      wedgenose skate, Dipturus whitleyi (Rajiformes: Rajidae), from Tasmania
      (Australia).
AB  - A new species of Prochristianella Dollfus, 1946 is described from the spiral
      intestine of the wedgenose skate, Dipturus whitleyi (Iredale) (Rajiformes:
      Rajidae), off the north-western coast of Tasmania (Australia). Prochristianella
      mattisi sp. n. is characterised by an acraspedote scolex, two oval bothria,
      elongate, bent bulbs, a retractor muscle inserting at the base of each bulb and
      the presence of gland-cells within the bulbs and prebulbar organs. The tentacular
      armature is typical heteroacanthous, heteromorphous, with a characteristic basal
      oncotaxy and a metabasal armature with hooks first increasing and then decreasing
      in size along each principle row. It can be differentiated from other species of
      Prochristianella by a combination of morphological characters, such as the
      metabasal tentacular armature with eight hooks per principle row, a unique basal
      armature without enlarged hooks on the basal swelling and genital pores slightly
      posterior to the mid-line of the segment. The description of P. mattisi sp. n.
      increases the number of known species within Prochristianella to 20, eight of
      which occur in Australian waters. A key for the identification to species within
      Prochristianella is provided.

PMID- 23951934
TI  - Analysis of the accuracy and precision of the McMaster method in detection of the
      eggs of Toxocara and Trichuris species (Nematoda) in dog faeces.
AB  - The aim of this study was to determine the accuracy and precision of McMaster
      method with Raynaud's modification in the detection of the eggs of the nematodes
      Toxocara canis (Werner, 1782) and Trichuris ovis (Abildgaard, 1795) in faeces of
      dogs. Four variants of McMaster method were used for counting: in one grid, two
      grids, the whole McMaster chamber and flotation in the tube. One hundred sixty
      samples were prepared from dog faeces (20 repetitions for each egg quantity)
      containing 15, 25, 50, 100, 150, 200, 250 and 300 eggs of T. canis and T. ovis in
      1 g of faeces. To compare the influence of kind of faeces on the results, samples
      of dog faeces were enriched at the same levels with the eggs of another nematode,
      Ascaris suum Goeze, 1782. In addition, 160 samples of pig faeces were prepared
      and enriched only with A. suum eggs in the same way. The highest limit of
      detection (the lowest level of eggs that were detected in at least 50% of
      repetitions) in all McMaster chamber variants were obtained for T. canis eggs (25
      250 eggs/g faeces). In the variant with flotation in the tube, the highest limit
      of detection was obtained for T. ovis eggs (100 eggs/g). The best results of the
      limit of detection, sensitivity and the lowest coefficients of variation were
      obtained with the use of the whole McMaster chamber variant. There was no
      significant impact of properties of faeces on the obtained results.
      Multiplication factors for the whole chamber were calculated on the basis of the
      transformed equation of the regression line, illustrating the relationship
      between the number of detected eggs and that of the eggs added to the'sample.
      Multiplication factors calculated for T. canis and T. ovis eggs were higher than
      those expected using McMaster method with Raynaud modification.

PMID- 23951935
TI  - [Spin-off effects of study abroad experience: feel pleasure in firsthand
      knowledge].

PMID- 23951936
TI  - [8-year-old complaining of numbness and fatigue of both legs].

PMID- 23951937
TI  - [Glutamate signaling and neural plasticity].
AB  - Proper functioning of the nervous system relies on the precise formation of
      neural circuits during development. At birth, neurons have redundant synaptic
      connections not only to their proper targets but also to other neighboring cells.
      Then, functional neural circuits are formed during early postnatal development by
      the selective strengthening of necessary synapses and weakening of surplus
      connections. Synaptic connections are also modified so that projection fields of
      active afferents expand at the expense of lesser ones. We have studied the
      molecular mechanisms underlying these activity-dependent prunings and the
      plasticity of synaptic circuitry using gene-engineered mice defective in the
      glutamatergic signaling system. NMDA-type glutamate receptors are critically
      involved in the establishment of the somatosensory pathway ascending from the
      brainstem trigeminal nucleus to the somatosensory cortex. Without NMDA receptors,
      whisker-related patterning fails to develop, whereas lesion-induced plasticity
      occurs normally during the critical period. In contrast, mice lacking the
      glutamate transporters GLAST or GLT1 are selectively impaired in the lesion
      induced critical plasticity of cortical barrels, although whisker-related
      patterning itself develops normally. In the developing cerebellum, multiple
      climbing fibers initially innervating given Purkinje cells are eliminated one by
      one until mono-innervation is achieved. In this pruning process, P/Q-type Ca2+
      channels expressed on Purkinje cells are critically involved by the selective
      strengthening of single main climbing fibers against other lesser afferents.
      Therefore, the activation of glutamate receptors that leads to an activity
      dependent increase in the intracellular Ca2+ concentration plays a key role in
      the pruning of immature synaptic circuits into functional circuits. On the other
      hand, glutamate transporters appear to control activity-dependent plasticity
      among afferent fields, presumably through adjusting extracellular glutamate
      concentrations to optimally reflect their different neural activities in
      postsynaptic target neurons. Thus, armed with both molecular mechanisms,
      functional neural circuits develop and mature during the early postnatal period.

PMID- 23951938
TI  - [Development of a training program for Japanese dyslexic children and its short
      term efficacy].
AB  - OBJECTIVE: The purpose of this study is to develop a computer training program of
      reading for the Japanese dyslexic children and to examine its short-term efficacy
      on their reading and writing abilities. METHODS: Fifteen dyslexic children
      underwent two sets of training programs, one for single-hiragana and non-word
      reading, and the other for the reading of real words, in which each hiragana was
      followed by the correctly read sound. Subjects were required to use a given
      program for five minutes a day for three weeks, switching to the other program
      after a three-week interval. Four kinds of reading test and one writing test were
      done at the beginning and end of each program period. RESULTS: The averages
      reading speeds increased, and the single-hiragana reading error average was lower
      after the training. Hiragana-writing errors also decreased, even though no
      writing procedure was involved in the programs. CONCLUSIONS: The results indicate
      the usefulness of these training programs as an early intervention of reading and
      writing for the Japanese dyslexic children.

PMID- 23951939
TI  - [Efficacy of repeated adrenocorticotropic hormone therapy in patients with
      intractable epileptic spasms].
AB  - OBJECTIVE: We examined the effectiveness of repeated adrenocorticotropic hormone
      (ACTH) therapy in short-term and long-term seizure control in patients with
      intractable epileptic spasms. METHODS: Twenty-five patients with intractable
      spasms, in whom epileptic seizures were not controlled or relapsed after the
      first ACTH therapy, were given repeated ACTH therapy. The short-term effect
      (seizure control longer than two months) of repeated ACTH therapy was analyzed,
      and the long-term effect was estimated by Kaplan-Meier method. RESULTS: Short
      term seizure control by repeated ACTH therapy was achieved in 13 of 25 patients
      (52.0%), and in 5 of 13 patients, seizures were controlled by ACTH therapy at
      higher doses compared with the first ACTH therapy. Short-term effectiveness was
      obtained in 76.5% of patients who had epileptic spasms alone at the time of the
      second ACTH therapy, but was ineffective in all 8 patients who had multiple types
      of seizures, with relapses within 2 months. Short-term effectiveness was not
      associated with clinical factors such as onset age, age of repeated ACTH
      treatment, and EEG findings. Regarding the long-term effect of repeated ACTH
      therapy, the period until seizure relapse was significantly longer in patients
      with epileptic spasms alone compared to patients with multiple seizure types.
      Spasms were controlled in 5 of 25 cases (20.0%) at the final observation. In
      patients with multiple seizure types and patients with onset age older than eight
      months, seizure control was not obtained. Long-term outcome was good in patients
      with treatment lag within 2 months. CONCLUSION: In repeated ACTH therapy, seizure
      type seems to be one of the major determinants for short- and long-term seizure
      outcome.

PMID- 23951940
TI  - [Changes in serum levels of selenium, zinc and copper in patients on a ketogenic
      diet using Ketonformula].
AB  - OBJECTIVE: Ketogenic diets tend to cause trace mineral deficiencies. Ketonformula
      is a foumula for a ketogenic diet developed by Meiji Co Ltd in Japan. No reports
      are available on the trace mineral deficiencies associated with a use of
      Ketonformula. METHODS: We monitored the serum levels of selenium, zinc and copper
      as well as the amount of the daily intake of these minerals before and at 6
      months after the initiation of the ketogenic diet with Ketonformula in six
      patients with intractable epilepsy associated with severe motor and intellectual
      disabilities. RESULT: The median serum selenium concentration decreased from 7.0
      (range, 6.5-12.3) microg/dl to 6.2 (5.4-10.9) microg/dl as a result of the 6
      month-treatment with Ketonformula (p < 0.05, Wilcoxon signed-rank test). The
      median daily selenium intake decreased from 17.8 (15.0-27.0) microg/day at the
      baseline to 5.5 (5.0-22.0) microg/day after 6 months on the diet (p < 0.05). The
      median serum zinc concentration increased slightly (from 66.0 (46.0-84.0)
      microg/dl to 68.0 (46.0-71.0) microg/dl), but the difference was not significant.
      The median daily zinc intake, however, significantly decreased from 4.2 (3.7-6.0)
      mg/day to 2.2 (2.0-3.0) mg/day (p < 0.05). The median serum copper concentration
      also showed no significant decrease (from 134.5 (119.0-168.0) microg/dl to 126.0
      (86.0-183.0) microg/dl). The median daily copper intakes, however, decreased
      significantly from 0.80 (0.35-1.30) mg/day to 0.30 (0.26-0.40) mg/day (p < 0.05).
      CONCLUSIONS: The decline of the serum selenium concentrations and daily enteral
      intakes of selenium, zinc, and copper after 6 months on Ketonformula suggested
      that patients on this ketogenic formula needs close monitoring as well as
      supplementation of these trace minerals.

PMID- 23951941
TI  - [Neurological sequelae of acute encephalopathy with febrile convulsive status
      epilepticus].
AB  - OBJECTIVE: The clinical characteristics of neurological sequelae in patients with
      acute encephalopathy with febrile convulsive status epilepticus (AEFCSE) was
      elucidated. METHODS: We retrospectively reviewed 8 patients, which were admitted
      to our hospital from 2002 to 2011. RESULTS: In the subacute phase, transient
      neurological symptoms, such as dystonia (n = 3), choreoathetosis (n = 2), oral
      tendency (n = 5) and unilateral spatial neglect (n = 6), appeared from 3 weeks
      after onset. Then, severe intellectual disability (n = 7), attention deficit (n =
      7), disturbance of communication skill (n = 7) and emotional disturbance (n = 2),
      persisted from one month after onset. Although seven patients resumed ambulatory
      abilities, six exhibited unstable gait without ataxia or muscular weakness. The
      neuroradiological findings on MRI corresponded to the clinical course. In the
      subacute phase, reversible bilateral signal changes were noted in the subcortical
      white matter (n = 8), caudate nuclei (n = 2), putamen (n = 1) and thalamus (n =
      1). In the chronic phase, diffuse cortical atrophy, predominantly in the fronto
      temporal lobes. Diffuse cortical atrophy suggested that the persistent
      neurological sequelae of AEFCSE represent cortical dysfunction. Therefore, we
      propose that the unstable gait in our patients was gait ataxia, being related to
      the frontal lobe dysfunction. CONCLUSIONS: These neurological findings of AEFCSE
      showed characteristic temporal changes, which should be considered in the
      development of rehabilitation programs.

PMID- 23951942
TI  - [Investigation of visiospatial disturbance after acute encephalopathy].
AB  - OBJECTIVE: We investigated the visiospatial disturbance in 103 children with
      acute encephalopathy at more than one year from the onset. METHODS: The patients
      were divided into two groups:group (1) with visiospacial disturbance (43 cases),
      group (2) without (60 cases). We checked the etiology, consciousness loss,
      complications and disabilities including higher cortical dysfunction in their
      medical charts. RESULTS: The average age of onset was 3 years 5 months in group
      (1), and that 2 years 8 months in group (2). Regarding the etiology, influenza
      infection, was most common (36 cases), and there was no statistical difference
      between two groups. The duration of consciousness loss was 10.8 days in group (1)
      and 7.7 days in group (2). The abnormal region on MRI brain and single photon
      emission computed tomography was mainly the occipital area in group (1) and the
      frontal area in group (2). Prominent complicating disabilities comprised higher
      cortical dysfunction, such as visiospatial disturbance in group (1) and
      interpersonal skill disturbance in group (2). The symptoms of visiospatial
      disturbance were difficulty in searching, writing, recognizing bumps, etc. After
      proper evaluation and rehabilitation programs, continuous performance of the
      programs was necessary in daily living. CONCLUSIONS: It is important for children
      with acute encephalopathy to be checked for visiospatial disturbance. An early
      rehabiitation approach should be taken for children with visiospatial
      disturbance.

PMID- 23951943
TI  - [Characteristics of women with epilepsy who developed polycystic ovary syndrome
      owing to the therapy with valproate sodium].
AB  - OBJECTIVE: The purpose of this study was to assess the characteristics of women
      with epilepsy who developed polycystic ovary syndrome (PCOS) owing to therapy
      with valproate sodium (VPA). METHODS: Our study comprised 77 patients on therapy
      with VPA--20 patients with PCOS and 57 without PCOS (control group). We assessed
      their epilepsy type, status of seizure control, and mental and physical statuses
      as well as the starting age, administration period, total dosage, and the highest
      value of blood concentration of VPA. RESULTS: As compared with the control group,
      the PCOS group showed significantly high rates of association with mental
      retardation, severe physical disabilities, and poor seizure control, and
      symptomatic generalized epilepsy. However, the starting age, administration
      period, total dosage, and the highest value of blood concentration of VPA were
      not significantly different between the 2 groups. Nineteen of the 20 patients
      with PCOS had characteristically high androstenedione levels. CONCLUSIONS: Our
      study demonstrated that refractory symptomatic generalized epilepsy, polypharmacy
      including VPA and severe motor and intellectual disabilities are risk factors of
      developing PCOS.

PMID- 23951944
TI  - [Three cases of human herpesvirus-6 encephalopathy showing hyperperfusion in the
      acute phase on SPECT].
AB  - Brain hypoperfusion observed on single-photon emission computed tomography
      (SPECT) is a typical finding in the acute phase of human herpesvirus-6 (HHV-6)
      encephalopathy. However, from 2004 to 2010, we encountered three cases of HHV-6
      encephalopathy in which hyperperfusion in the area of the brain lesion was
      observed on SPECT performed within 48 hours after disease onset. The
      hyperperfusion in the brain was followed by hypoperfusion in the recovery phase.
      These cases suggest that hyperperfusion may appear in damaged areas prior to the
      hypoperfusion that is normally associated with HHV-6 encephalopathy.

PMID- 23951945
TI  - [A one-year-old male infant with sleep-associated febrile myoclonus].
AB  - Febrile myoclonus is a benign neurological symptom induced by fever. The
      physiological mechanism is unknown. We herein report a 1 year and 7 months old
      male patient with intermittent jerks of the whole body during a high fever caused
      by acute otitis media. He experienced more than 50 jerks over a period of 2 days.
      The jerks appeared only during sleep. He showed no impairment of consciousness
      and no abnormalities in neurological examination, blood examination,
      electroencephalogram, or brain MRI findings. We diagnosed him with febrile
      myoclonus. The myoclonic jerks disappeared as the fever decreased without
      neurological sequelae. To the best of our knowledge, febrile myoclonus only
      during sleep has never been reported. To clarify the pathophysiology of febrile
      myoclonus, we should focus on the relationship between the myoclonus and the
      sleep/awake states.

PMID- 23951946
TI  - [Pre-evening meal administration of tacrolimus improved refractory ocular
      symptoms in two young children with latent general myasthenia gravis].
AB  - We report two patients with latent general myasthenia gravis (MG) with refractory
      ocular symptoms who were successfully treated with pre-evening meal
      administration of tacrolimus. Patient 1 was a 4-year-old girl with persistent
      ocular symptoms despite high-dose steroid therapy and thymectomy. Oral tacrolimus
      was initiated at the age of 3 years, which was resulted in complete resolution of
      symptoms. After one year, hemilateral ptosis recurred. The plasma consentration
      of tacrolimus was very low, probably due to sudden weight gain. Increasing the
      dose and a change from post- to pre-evening meal administration of tacrolimus
      enabled maintenance of its concentration and complete control of ocular symptoms.
      Patient 2 was a 2-year-old boy whose symptoms were refractory to steroid therapy
      after his first relapse. Since post-meal administration of tacrolimus provided
      partial benefit, the closing schedule was changed to pre-evening meal
      administration, with good results. Neither patient had adverse effects of
      tacrolimus. It is difficult to maintain an effective tacrolimus concentration in
      children due to marked growth and rapid metabolic rates. Pre-evening meal
      administration of tacrolimus is an easy, safe and useful method of treatment in
      MG young children.

PMID- 23951947
TI  - [A case of alternating hemiplegia of childhood effectively treated with goreisan
      of kampo].

PMID- 23951948
TI  - Altruism as an indicator of good parenting quality in long-term relationships:
      further investigations using the Mate Preferences Towards Altruistic Traits
      Scale.
AB  - Research has shown that altruism plays a role in mate choice, and recent studies
      suggest it is most important for long-term relationships. This study examined
      whether altruism is preferred for long-term relationships for both males and
      females. This was achieved using two versions of the Mate Preferences Towards
      Altruistic Traits (MPAT) scale that assessed preferences for short-term and long
      term relationships. Both males and females significantly preferred altruistic
      mates for long-term relationships, and the size of this preference was greater
      than for other traits in mate choice. This provides support for previous findings
      that state that altruism conveys information about an individual's
      partner/parenting qualities or good character.

PMID- 23951949
TI  - Gender and gender role differences in self- and other-estimates of multiple
      intelligences.
AB  - This study examined participant gender and gender role differences in estimates
      of multiple intelligences for self, partner, and various hypothetical,
      stereotypical, and counter-stereotypical target persons. A general population
      sample of 261 British participants completed one of four questionnaires that
      required them to estimate their own and others' multiple intelligences and
      personality traits. Males estimated their general IQ slightly, but mathematic IQ
      significantly higher than females, who rated their social and emotional
      intelligence higher than males. Masculine individuals awarded themselves somewhat
      higher verbal and practical IQ scores than did female participants. Both
      participant gender and gender role differences in IQ estimates were found, with
      gender effects stronger in cognitive and gender role than in "personal" ability
      estimates. There was a significant effect of gender role on hypothetical persons'
      intelligence evaluations, with masculine targets receiving significantly higher
      intelligence estimates compared to feminine targets. More intelligent
      hypothetical figures were judged as more masculine and less feminine than less
      intelligent ones.

PMID- 23951950
TI  - Taking the high (or low) road: a quantifier priming perspective on basic
      anchoring effects.
AB  - Current explanations of basic anchoring effects, defined as the influence of an
      arbitrary number standard on an uncertain judgment, confound numerical values
      with vague quantifiers. I show that the consideration of numerical anchors may
      bias subsequent judgments primarily through the priming of quantifiers, rather
      than the numbers themselves. Study 1 varied the target of a numerical comparison
      judgment in a between--participants design, while holding the numerical anchor
      value constant. This design yielded an anchoring effect consistent with a
      quantifier priming hypothesis. Study 2 included a direct manipulation of vague
      quantifiers in the traditional anchoring paradigm. Finally, Study 3 examined the
      notion that specific associations between quantifiers, reflecting values on
      separate judgmental dimensions (i.e., the price and height of a target) can
      affect the direction of anchoring effects. Discussion focuses on the nature of
      vague quantifier priming in numerically anchored judgments.

PMID- 23951951
TI  - The dual process model of ideology and prejudice: a longitudinal test during a
      global recession.
AB  - This study tested the pathways between personality, social worldviews, and
      ideology, predicted by the Dual Process Model (DPM) of ideology and prejudice.
      These paths were tested using a full cross-lagged panel design administered to a
      New Zealand community sample in early 2008 (before the effects of the global
      financial crisis reached New Zealand) and again in 2009 (when the crisis was near
      its peak; n = 247). As hypothesized, low openness to experience predicted
      residualized change in dangerous worldview, which in turn predicted right-wing
      authoritarianism (RWA). Low agreeableness predicted competitive worldview, which
      in turn predicted social dominance orientation (SDO). RWA and SDO also exerted
      unexpected reciprocal effects on worldviews. This study provides the most
      comprehensive longitudinal test of the DPM to date, and was conducted during a
      period of systemic instability when the causal effects predicted by the DPM
      should be, and were, readily apparent.

PMID- 23951952
TI  - Maximizing relationship possibilities: relational maximization in romantic
      relationships.
AB  - Using Rusbult's (1980) investment model and Schwartz's (2000) conceptualization
      of decision maximization, we sought to understand how an individual's propensity
      to maximize his or her decisions factored into investment, satisfaction, and
      awareness of alternatives in romantic relationships. In study one, 275
      participants currently involved in romantic relationships completed measures of
      maximization, satisfaction, investment size, quality of alternatives, and
      commitment. In study two, 343 participants were surveyed as part of the creation
      of a scale of relational maximization. Results from both studies revealed that
      the tendency to maximize (in general and in relationships specifically) was
      negatively correlated with satisfaction, investment, and commitment, and
      positively correlated with quality of alternatives. Furthermore, we found that
      satisfaction and investments mediated the relationship between maximization and
      relationship commitment.

PMID- 23951954
TI  - Effects of playing video games on perceptions of one's humanity.
AB  - According to self-perception theory, individuals infer their characteristics by
      observing their own behavior. In the present research, the hypothesis is examined
      whether helping behavior increases perceptions of one's own humanity even when
      help is given that does not benefit a real person. In fact, two studies revealed
      that playing a prosocial video game (where the goal is to help and care for other
      game characters) led to increased perceptions of the player's own humanity (in
      particular, for positive humanity traits). Results also revealed that playing a
      violent, relative to a neutral, video game decreased perceptions of humanity on
      positive humanity traits and increased perceptions of humanity on negative
      humanity traits. Taken together, it appears that being helpful while playing
      video games leads to the perception of being more human, whereas being harmful
      while playing video games leads players to perceive themselves negatively.

PMID- 23951953
TI  - Religiosity and prejudice: different patterns for two types of religious
      internalization.
AB  - The literature on the relationship between religiosity and prejudice has shown
      inconsistent findings. We argue that it is necessary to distinguish between
      different types of religiosity and that its relationship with prejudice is
      mediated by different values. Results of two studies conducted in Italy show that
      identified religiosity and introjected religiosity predict different levels of
      prejudice toward Muslim immigrants. Moreover, the negative relationship between
      identified religiosity and prejudice was mediated by prosocial values, whereas
      valuing conformity mediated the positive relationship between introjected
      religiosity and prejudice. The results show that it is possible to better
      understand the relationship between religiosity and prejudice by disentangling
      the different ways of being religious.

PMID- 23951955
TI  - Retaining authenticity in the rush to merge.

PMID- 23951956
TI  - New partnerships for stronger mission.

PMID- 23951957
TI  - Troubled waters: remaining a beacon amid change.

PMID- 23951958
TI  - The right fit: stand-alones and small systems must get the questions right.

PMID- 23951959
TI  - Extending the mission remotely: integrating the values of catholic health care in
      new models, emerging markets.

PMID- 23951960
TI  - Dignity health: new name, same mission.

PMID- 23951961
TI  - KentuckyOne: building upon cultural legacy.

PMID- 23951962
TI  - Rethinking ethics: employed physicians, ACOs, high costs prompt review.

PMID- 23951963
TI  - The vision of Vatican II: alive in Catholic health care.

PMID- 23951964
TI  - Our sponsors: yesterday, today and tomorrow.

PMID- 23951965
TI  - More than a partnership: new business model in Haiti, too.

PMID- 23951966
TI  - The 'sweet spot' of catholic health care ministry leadership.

PMID- 23951967
TI  - A summary: Caritas in communion.

PMID- 23951968
TI  - Catholic health care must stand in the middle.

PMID- 23951969
TI  - Community benefit needs board oversight.

PMID- 23951970
TI  - Christus health designs with mission in mind: work spaces focus on values--and
      associates.

PMID- 23951971
TI  - Clinical networks.

PMID- 23951972
TI  - New oral anticoagulants for non-valvular atrial fibrillation--safety issues.

PMID- 23951973
TI  - Sudden unexplained death in childhood. An audit of the quality of autopsy
      reporting.
AB  - Cases of sudden unexplained death in childhood (SUDC) in Ireland in children aged
      > 1 year and < 5 years were examined in order to assess the quality of autopsy
      reporting. All SUDC cases are notified to and documented by the National Sudden
      Infant Death Register (NSIDR) in Ireland along with all cases of sudden infant
      death syndrome (SIDS) referring to sudden infant deaths less than one year of
      age. The database of the NSIDR in Ireland was interrogated and cases of SIDS and
      SUDC were compared over a fifteen-year period (1995-2009). SIDS cases whose
      autopsies were conducted in the same hospital in the same year as the index SUDC
      case were used for comparison. The autopsy report for each case was examined and
      modified Rushton (MR) score(s1) calculated. MR scores were compared along with
      the number of paediatric pathology prosectors and the year of autopsy examination
      between the two groups. 45 cases were registered as SUDC (age 52 - 152 weeks)
      between 1995-2009. Autopsy reports were available for 43/45 (95%) of these. 43
      SIDS cases from the same year and site of autopsy were used for comparison.
      Overall MR scores were higher in the SIDS cases, with 29/43 (67%) cases obtaining
      the minimum arbitrary score (MAS) of > 300 compared to 25/43 (58%) of SUDC cases.
      Paediatric pathologists in specialist centres carried out similar numbers of SIDS
      autopsies and SUDC autopsies (46% SIDS, 44% SUDC). Autopsies carried out by
      paediatric pathologists in specialist centres met the MAS in 19/21 (90%) SIDS
      cases and 18/19 (95%) SUDC cases. Based on our findings we recommend referral of
      all SUDC cases to specialist centres for optimal autopsy examination and
      investigation, and that cases of sudden unexpected death in children over 1 year
      of age are investigated according to the same guidelines as are used for
      unexpected death under one year of age.

PMID- 23951974
TI  - The epidemiology of assault-related hospital in-patient admissions and ED
      attendances.
AB  - The aim of this study was to describe the epidemiology and impact of serious
      assault warranting in-patient care over six years and its impact on ED
      attendances in a large teaching hospital in Dublin over 2 years. There were
      16,079 emergency assault-related inpatient hospital discharges reducing from 60.1
      per 100,000 population in 2005 to 50.6 per 100,000 population in 2010. The median
      length of stay was 1 day (1-466) representing 49,870 bed days. The majority were
      young males (13,921, 86.6%; median age 26 years). Overall crime figures showed a
      similar reduction. However, knife crimes did not reduce over this period. Data on
      ED attendances confirmed the age and gender profile and also showed an increase
      at weekends. Alcohol misuse was recorded in 2,292/16079 (14%) of in-patient cases
      and 242/2484 (10%) in ED attendances. An inter-sectoral preventative approach
      specifically targeting knife crime is required to reduce this burden on health
      services.

PMID- 23951975
TI  - Apparent improvement in survival for carcinoma of the cervix following the
      introduction of chemoradiation--a Will Rogers phenomenon.
AB  - The improved survival for bulky cervical cancers (> 4cm) reported with
      combination platinum based chemoradiation (1999) prompted a move away from
      surgery as these cases frequently received adjuvant radiotherapy and were exposed
      to the morbidity of multimodality treatment. The period pre-1999 (Group 1) was
      compared with post-1999 (Group 2) when chemoradiation was the preferred treatment
      for bulky operable cervical cancer. Significantly more cases were treated
      surgically among Group 1 compared with Group 2 (79% vs. 62%; P < 0.001).
      Switching from surgery to radiotherapy improved survival in both treatment
      categories (73% vs. 78% and 37% vs. 44%, respectively) but with no improvement in
      overall survival (70%/ov.s 70%). Survival (86%) was similar in both groups among
      surgically treated women with tumors < 4 cm, but significantly more in Group 2
      with negative nodes received postoperative adjuvant chemoradiotherapy (Groups 1
      vs. 2; 16% vs.37.5%: P < 0.001) and overall the surgically treated patients
      received more not less multimodality treatment (46.5% vs. 59%; P = 0.7).

PMID- 23951976
TI  - Structured care of diabetes in general practice: a qualitative study of the
      barriers and facilitators.
AB  - This qualitative study explored general practitioner's and practice nurse's
      perceptions of barriers and facilitators to the proposed transfer of diabetes
      care to general practice. Qualitative data were collected through five focus
      groups. Participants included GPs (n = 55) and practice nurses (n = 11)
      representing urban (44%), rural (29%) and mixed (27%) practices, in the Irish Mid
      West region. Barriers and facilitators were mentioned 631 times (100%). Barriers
      were mentioned 461 times (73%), facilitators 170 times (27%). The most frequently
      identified barriers were lack of financial incentive (119/631; 19%), lack of
      access to secondary resources (93/631; 15%), lack of staff and increased workload
      (59/631; 9%) and time constraints (52/631; 8%). Identified facilitators were
      access to secondary care (49/631;7.8%), the holistic nature of general practice
      and continuity of care (48/631;7.6%). Although many are enthusiastic, there
      remains significant reluctance among GPs and practice nurses to take
      responsibility for diabetes care without addressing these barriers.

PMID- 23951977
TI  - Implementation of thromboprophylaxis guidelines.
AB  - Venous thromboembolism (VTE) remains one of the leading direct causes of maternal
      death. Risk factors for VTE and prophylaxis guidelines have been highlighted by
      the Royal College of Obstetricians and Gynaecologists (RCOG). A cross sectional
      study was completed in Cork University Maternity Hospital (CUMH) to determine
      pattern of VTE risk and compliance with 2004 RCOG guidelines. 364 women's charts
      were reviewed. Forty percent (n = 145) were at risk for VTE, 69% (n = 100) of
      these received thromboprophylaxis but only 54% (n = 54) received the correct
      weight adjusted dose. Three of four morbidly obese women in this study received
      recommended thromboprophylaxis but none at the appropriate dose. Only 67% (n =
      245) had a recorded body mass index (BMI). Increased BMI is a significant risk
      factor for VTE and should be measured and recorded at the booking visit.
      Awareness of the risks for VTE and the need for appropriate dosing should be
      improved.

PMID- 23951978
TI  - Attitudes and intentions of current anaesthetic trainees.
AB  - We report the results of a survey of Irish anaesthetic specialist trainees to
      establish their future training intentions, their interest in seeking a
      Consultant position in Ireland and identification of factors that may reduce the
      attractiveness of future employment in the HSE. 149 responses were received (71%
      of trainees). 137 (92%) are likely to complete further training abroad, but only
      24 (16.1%) are definitely planning to return to work in Ireland. Factors, in
      order of importance that influence their return to Ireland include equivalence of
      all Consultants, salary level and availability of flexible work practices. Almost
      all (131 - 91%) would only consider working in Ireland at Consultant level. These
      results reveal that the current cohort of specialist trainees do not consider
      Ireland an attractive place to work, and any further diminution of the current
      Consultant grade will only serve to worsen this perception.

PMID- 23951979
TI  - Inflammatory bowel disease and thromboembolism. Is inflammation at the centre of
      the clot?
AB  - Thromboembolic events are well recognised in patients with inflammatory bowel
      disease (IBD). We present three cases which highlight the need for vigilance with
      respect to this complication. We also propose that consideration be given to re
      evaluating disease activity in those patients who develop thromboembolic
      complications.

PMID- 23951980
TI  - Hyaline vascular Castleman's disease involving the biliary tract.
AB  - We report a case of Castleman's Disease (CD), hyaline vascular subtype involving
      the biliary tract with obstruction. A 43 year old man presented with a 5 week
      history of abdominal and back pain with biliary obstructive symptoms. He was
      jaundiced with persistently high LFTs. Radiological investigation revealed a
      stricture in the extrahepatic biliary tract. The clinical impression at the time
      was of sclerosing cholangitis with bile duct cholangiocarcinoma. A Whipple's
      procedure was performed. Histology and immunohistochemistry supported the
      histologic diagnosis of CD of hyaline vascular subtype. There was no evidence of
      disease elsewhere and the patient was disease free after a 6 year follow-up. Our
      case describes the hyaline vascular subtype of CD, a relatively rare disease
      occurring in a previously undescribed location.

PMID- 23951981
TI  - Acute cerebellitis associated with dual influenza A (H1N1) and B infection.
AB  - We describe the case of a 6-year old girl who presented to our Emergency
      Department (ED) with acute onset of ataxia and speech disturbance. Investigative
      workup included a nasopharyngeal aspirate (NPA) which was influenza A (H1N1) and
      B positive during the 2010/2011 influenza season. Magnetic resonance imaging
      (MRI) of the brain confirmed findings consistent with cerebellitis.

PMID- 23951982
TI  - Percutaneous transhepatic cholecystoscopic gallstone fragmentation: a novel
      approach for the medically unfit patient?
AB  - Management of the surgically unfit patient with symptomatic cholelithiasis can be
      fraught with difficulty. We describe the case of on such gentleman in whom
      percutaneous transhepatic cholecystoscopy was used to completely fragment a large
      gallbladder calculus through the use of a nephroscope and Swiss lithoclast
      Master.

PMID- 23951983
TI  - Qutenza patch--our early experience.
AB  - Qutenza is a high potency capsaicin topical patch which has been recommended for
      the treatment of peripheral neuropathic pain. The aim of this study was to assess
      our selected patients' response to Qutenza application. All patients had their
      dynamic pain score recorded prior to application and were asked to fill in a
      standardised questionnaire for three months post application. Patients were also
      asked to document any changes to the character of their pain, changes in sleep,
      activities of daily living and mood as well as any changes to their medication
      usage. 21 patients had Qutenza applied in a 5 month period. 17 patients completed
      the questionnaire in a 5 month period. We found that the mean overall reduction
      in pain score at 3 months was 32.7%. 8 of our patients (47%) reported improved
      sleep, activities of daily living and mood. 6 patients (35%) reported a reduction
      in medication use, while 7 (41%) reported an improvement in the character of
      their pain.

PMID- 23951984
TI  - Mortality due to SUDEP and status epilepticus.
AB  - Mortality in patients with epilepsy (PWE) is increased compared to the general
      population. For this reason the National Programme of Epilepsy Care, which was
      established under the Health Service Executive's National Director for Clinical
      Strategy and Programmes, identified a reduction in mortality from epilepsy as a
      key quality metric to monitor the success of the programme. The increased
      mortality is greatest in the first years after diagnosis where it is
      predominantly related to the underlying cause but there remains a persistent
      elevation in mortality rates especially amongst those with longstanding epilepsy.
      This group of patients is more likely to die from epilepsy, predominantly sudden
      unexpected death in epilepsy (SUDEP) or status epilepticus (SE). This paper
      identifies a number of studies on mortality in epilepsy from SE and SUDEP and
      uses this data to generate an estimate for annual mortality from SUDEP and SE in
      Ireland. These estimates indicate that mortality in patients with epilepsy due to
      SUDEP and SE account for between 48 and 162 deaths per year in Ireland and
      sources of mortality information currently available possibly underestimate the
      numbers involved especially if deaths due to non-convulsive status are included.

PMID- 23951985
TI  - Compliance with the HSE policy on vitamin D supplementation for infants.

PMID- 23951986
TI  - Program planning for an assisted living community.
AB  - Occupational therapy has long had a vested interest in activity programming for
      the elderly. During the past, this interest has been largely confined to adult
      day care centers for community dwelling elderly, and to nursing homes for long
      term care of the elderly. In light of the interest generated by the recent entry
      of assisted living into the housing continuum, program models and understanding
      of the population of people who choose this option are of interest. This article
      introduces one model of wellcare for assisted living residents and describes a
      population of 626 residents in approximately 30 Morningside assisted living
      communities dispersed over the Southeast. The Healthy Generation model outlined
      in this article emphasizes five separate but inter-related domains that have been
      shown to impact the quality of life of aging individuals. Through the use of a
      multidimensional instrument, these domains (intellectual, social, physical,
      spiritual and emotional) are surveyed at the time each resident moves into a
      Morningside community. The resulting picture of the population is utilized by the
      assisted living program planners to create a monthly balanced calendar that
      intentionally engages each domain to support and enhance resident function and
      well being. This model has a direct bearing on practice of geriatric occupational
      therapy and this emerging area of practice. 

PMID- 23951987
TI  - Oral motor feeding in the neonatal intensive care unit: exploring perceptions of
      parents and occupational therapists.
AB  - The purpose of this qualitative study was to explore the perceptions of three
      occupational therapists and three parents regarding occupational therapy services
      provided in the neonatal intensive care unit. Data were obtained through
      participant interviews. Role of the occupational therapist, parent training, and
      time spent with parents were themes that emerged from the therapist interviews.
      Themes from the parent interviews included occupational therapy intervention and
      treatment, time spent with occupational therapist, and perceptions. A cross-case
      analysis addressed two common themes: amount of time spent in parent training and
      perceptions of training provided. Implications for occupational therapy practice
      in the neonatal intensive care unit are discussed. 

PMID- 23951988
TI  - The Impact of Occupational Therapy on a Child's Playfulness.
AB  - The constant changing health care system has made it imperative for occupational
      therapists (OTs) to examine the effectiveness of treatment interventions with
      children. Few studies exist examining play as the desired outcome of the
      intervention. Previous studies in occupational therapy (OT) have focused on the
      motor aspects of play in children (Anderson, Hinojosa & Strauch, 1987; Florey,
      1981; Morrison, Bundy, & Fisher, 1991). In these studies, the researchers
      hypothesize that improving motor skills will improve play skills in children. OTs
      frequently evaluate play using the Preschool Play Scale (PPS) (Bledsoe &
      Shephard, 1982; Knox, 1997) which provides a developmental age for play skills.
      Therapists also use developmental assessments designed to examine the skills used
      during play (Bundy, 1991). Skills used in play are important but fail to look at
      a child's approach or attitude during play. A child's approach to activities of
      play is termed "playfulness" (Bundy, 1997). The Test of Playfulness (TOP) (Bundy,
      1997) was developed to measure this construct. The TOP provides information that
      can assist therapists working with children in designing measurable playfulness
      goals. This study examined the playfulness of four children who received OT
      intervention specifically designed to improve play behaviors in comparison to
      four children who did not receive this intervention. The results provide
      therapists with information and insight for treating children with play deficits.
      This information will help therapists design effective treatment to increase
      playfulness in children. 

PMID- 23951989
TI  - The relationship among demographic variables, professionalism, and level of
      involvement in a state occupational therapy association.
AB  - Research on professional occupations has defined varying criteria that an
      occupation must meet to be considered a profession. Involvement by the members in
      their professional organization is a recurrent theme. A questionnaire consisting
      of Hall's Occupational Inventory, an involvement scale, and a demographic survey
      was used to determine the relationship among three factors of the Indiana
      Occupational Therapy Association members: (a) demographics, (b) professional
      attributes, and (c) involvement in a state occupational therapy organization.
      Determining these relationships is significant for understanding membership and
      involvement in a state occupational therapy association. Findings indicated
      significant differences in terms of hourly involvement in a state occupational
      therapy association between respondents with entry-level and post-professional
      degrees and respondents who were married and those who were not married. 

PMID- 23951990
TI  - Leisure assessment in occupational therapy: an exploratory study.
AB  - Occupational therapy asserts that leisure, along with self-care and work, is a
      primary occupation of individuals and essential to occupational functioning. The
      purpose of this study was to explore the leisure assessment practices of
      occupational therapists in a variety of settings. A telephone survey, developed
      by the researchers, was administered to 105 occupational therapists in North
      Carolina, Pennsylvania, and Virginia. In addition, face to face interviews were
      conducted with 15 occupational therapists using the telephone survey as a guide.
      The results indicated that therapists report assessing leisure primarily through
      informal methods, especially through interview/discussion with their clients. The
      frequency with which they assessed leisure was significantly correlated with how
      much they valued leisure in their practice of occupational therapy. Lastly,
      therapists practicing in psychosocial areas valued leisure significantly more
      than those practicing in physical disabilities. 

PMID- 23951991
TI  - Care giving as an occupational role in the dying process.
AB  - Being involved in the death and dying process as a professional, family member,
      friend, or patient means taking on an occupational role that will impact one's
      life. Types of occupational roles associated with death and dying, and how these
      roles influence the participants, are explored in relation to concepts presented
      in the Model of Human Occupation. Also addressed is the potential for a care
      giving role to bring on distress in the form of role imbalance or role changes,
      or because of inability to adequately fulfill the role. Suggestions for seeking
      relative balance within and among roles are presented. 

PMID- 23951992
TI  - Predictors of organizational commitment among certified occupational therapy
      assistants.
AB  - The purpose of this correlational research study was to provide insights into
      specific extrinsic organizational rewards, extrinsic social rewards, and
      intrinsic rewards that lead to certified occupational therapy assistants' (COTA)
      organizational commitment, and how managers and recruiters can utilize this
      knowledge in developing more effective COTA recruitment and retention strategies.
      The target population for this investigation included COTAs who worked full-time
      in North Carolina, South Carolina, and Virginia and were members of the American
      Occupational Therapy Association. Findings from this study indicated that
      predictors of COTAs' organizational commitment were determined by intrinsically
      rewarding job tasks that were supported by their work environment, salary, and
      promotional opportunities. 

PMID- 23951993
TI  - What is a worthy goal of occupational therapy?
AB  - The construct of functional independence in performance areas has become what
      some might consider the hallmark of occupational therapy practice. This
      construct, as a predominant goal, or even ideal, of occupational therapy,
      however, embodies philosophical assumptions that bear scrutiny. For example, do
      clients and therapists conceive of function in the same way? When we speak of our
      clients being independent, do we mean they perform without any help, or do we
      mean they need appropriate help from persons or technology? In this paper I
      explore the assumptions underlying the construct of functional independence in
      performance areas. Further, I clarify why helping clients attain wholeness,
      autonomy, meaning, and purposiveness despite non-function and dependence forms a
      better principle of occupational therapy. 

PMID- 23951994
TI  - The power and flow of occupation illustrated through scrapbooking.
AB  - This paper discusses the concept of occupation by summarizing the theoretical
      work of Wilcock, the recent discussions of the power of occupation by Pierce, and
      the by-products of occupation by Crabtree. Tying the idea of optimal experiences
      to occupation, photo scrapbooking is used as an illustration of the power and
      flow of occupation by using excerpts of individuals enjoying scrapbooking. 

PMID- 23951996
TI  - Mechanical properties of the brain-skull interface.
AB  - Knowledge of the mechanical properties of the brain-skull interface is important
      for surgery simulation and injury biomechanics. These properties are known only
      to a limited extent. In this study we conducted in situ indentation of the sheep
      brain, and proposed to derive the macroscopic mechanical properties of the brain
      skull interface from the results of these experiments. To the best of our
      knowledge, this is the first ever analysis of this kind. When conducting in situ
      indentation of the brain, the reaction force on the indentor was measured. After
      the indentation, a cylindrical sample of the brain tissue was extracted and
      subjected to uniaxial compression test. A model of the brain indentation
      experiment was built in the Finite Element (FE) solver ABAQUSTM. In the model,
      the mechanical properties of the brain tissue were assigned as obtained from the
      uniaxial compression test and the brain-skull interface was modeled as linear
      springs. The interface stiffness (defined as sum of stiffnesses of the springs
      divided by the interface area) was varied to obtain good agreement between the
      calculated and experimentally measured indentor force-displacement relationship.
      Such agreement was found to occur for the brain-skull interface stiffness of
      11.45 Nmm-1/mm2. This allowed identification of the overall mechanical properties
      of the brain-skull interface.

PMID- 23951997
TI  - Association dynamics and linear and nonlinear optical properties of an N
      acetylaladanamide probe in a POPC membrane.
AB  - Along with the growing evidence that relates membrane abnormalities to various
      diseases, biological membranes have been acknowledged as targets for therapy. Any
      such abnormality in the membrane structure alters the membrane potential which in
      principle can be captured by measuring properties of specific optical probes.
      There exists by now many molecular probes with absorption and fluorescence
      properties that are sensitive to local membrane structure and to the membrane
      potential. To suggest new high-performance optical probes for membrane-potential
      imaging it is important to understand in detail the membrane-induced structural
      changes in the probe, the membrane association dynamics of the probe, and its
      membrane-specific optical properties. To contribute to this effort, we here study
      an optical probe, N-acetylaladanamide (NAAA), in the presence of a POPC lipid
      bilayer using a multiscale integrated approach to assess the probe structure,
      dynamics, and optical properties in its membrane-bound status and in water
      solvent. We find that the probe eventually assimilates into the membrane with a
      specific orientation where the hydrophobic part of the probe is buried inside the
      lipid bilayer, while the hydrophilic part is exposed to the water solvent. The
      computed absorption maximum is red-shifted when compared to the gas phase. The
      computations of the two-photon absorption and second harmonic generation cross
      sections of the NAAA probe in its membrane-bound state which is of its first kind
      in the literature suggest that this probe can be used for imaging the membrane
      potential using nonlinear optical microscopy. 

PMID- 23951998
TI  - Surface modification of a ZnO electron-collecting layer using atomic layer
      deposition to fabricate high-performing inverted organic photovoltaics.
AB  - A ripple-structured ZnO film as the electron-collecting layer (ECL) of an
      inverted organic photovoltaic (OPV) was modified by atomic layer deposition (ALD)
      to add a ZnO thin layer. Depositing a thin ZnO layer by ALD on wet-chemically
      prepared ZnO significantly increased the short-circuit current (Jsc) of the OPV.
      The highest power conversion efficiency (PCE) of 7.96% with Jsc of 17.9 mA/cm2
      was observed in the inverted OPV with a 2-nm-thick ALD-ZnO layer, which quenched
      electron-hole recombination at surface defects of ZnO ripples. Moreover, an ALD
      ZnO layer thinner than 2 nm made the distribution of electrical conductivity on
      the ZnO surface more uniform, enhancing OPV performance. In contrast, a thicker
      ALD-ZnO layer (5 nm) made the two-dimensional distribution of electrical
      conductivity on the ZnO surface more heterogeneous, reducing the PCE. In
      addition, depositing an ALD-ZnO thin layer enhanced OPV stability and initial
      performance. We suggest that the ALD-ZnO layer thickness should be precisely
      controlled to fabricate high-performing OPVs.

PMID- 23951999
TI  - Effects of magnetite nanoparticles on soybean chlorophyll.
AB  - Nanoparticles (NPs) have emerged as one of the most innovative and promising
      application in agriculture. Since plants are recognized as essential component of
      all ecosystems, the effects of NPs on plants may pave a new insight to the
      ecosystems. Here, uptake and translocation of superparamagnetic iron oxide NPs
      (SPIONs), with various surface charges, on soybean has been probed; in addition,
      the effects of SPIONs on variations of chlorophyll, in hydroponic condition,
      together with their ability for reduction of iron deficiency chlorosis were
      explored. We find that SPIONs, which were entered and translocated in the
      soybean, increased chlorophyll levels, with no trace of toxicity. Furthermore, it
      was found that physicochemical characteristics of the SPIONs had a crucial role
      on the enhancement of chlorophyll content in subapical leaves of soybean. The
      equivalent ratio of chlorophyll a to b, in all treatments with conventional
      growth medium iron chelate and SPIONs (as iron source), indicated no significant
      difference on the photosynthesis efficiency. Finally, it was observed that the
      effect of SPIONs on the soybean chlorophyll content may have influence on both
      biochemical and enzymatic efficiency in different stages of the photosynthesis
      reactions. 

PMID- 23952000
TI  - Hierarchically structured microfibers of "single stack" perylene bisimide and
      quaterthiophene nanowires.
AB  - Organic nanowires and microfibers are excellent model systems for charge
      transport in organic semiconductors under nanoscopic confinement and may be
      relevant for future nanoelectronic devices. For this purpose, however, the
      preparation of well-ordered organic nanowires with uniform lateral dimensions
      remains a challenge to achieve. Here, we used the self-assembly of oligopeptide
      substituted perylene bisimides and quaterthiophenes to obtain well-ordered
      nanofibrils. The individual nanofibrils were investigated by spectroscopic and
      imaging methods, and the preparation of hierarchically structured microfibers of
      aligned nanofibrils allowed for a comprehensive structural characterization on
      all length scales with molecular level precision. Thus, we showed that the
      molecular chirality resulted in supramolecular helicity, which supposedly serves
      to suppress lateral aggregation. We also proved that, as a result, the individual
      nanofibrils comprised a single stack of the pi-conjugated molecules at their
      core. Moreover, the conformational flexibility between the hydrogen-bonded
      oligopeptides and the pi-pi stacked chromophores gave rise to synergistically
      enhanced strong pi-pi interactions and hydrogen-bonding. The result is a
      remarkably tight pi-pi stacking inside the nanofibrils, irrespective of the
      electronic nature of the employed chromophores, which may render them suitable
      nanowire models to investigate one-dimensional charge transport along defined pi
      pi stacks of p-type or n-type semiconductors. 

PMID- 23952001
TI  - Women, power, advance.

PMID- 23952002
TI  - Reply: prospective studies to show possible benefits with tests for rupture of
      membranes (ROM) in equivocal ROM are still missing.

PMID- 23952003
TI  - Presenilin 2 influences miR146 level and activity in microglia.
AB  - Microglia, the resident innate immune cells of the CNS, are the primary defenders
      against microbes and critical to CNS remodeling. Dysregulation of microglial
      behavior can lead to unchecked pro-inflammatory activity and subsequent
      neurodegeneration. The molecular mechanisms leading to chronic inflammation and
      microglial dysfunction in neurodegenerative diseases are not well-understood. It
      is known that patients with Presenilin 2 (PS2) mutations develop autosomal
      dominant Alzheimer disease. We have shown that a lack of normal PS2 function is
      associated with exaggerated microglia pro-inflammatory responses in vitro. To
      identify pathways by which PS2 regulates microglia and determine how PS2
      dysfunction may lead to altered inflammatory pathways, we pursued an unbiased
      array approach to assess differential expression of microRNAs between murine PS2
      knockout (KO) and wild-type microglia. We identified miR146, a negative regulator
      of monocyte pro-inflammatory response, as constitutively down-regulated in PS2 KO
      microglia. Consistent with a state of miR146 suppression, we found that PS2 KO
      microglia express higher levels of the miR146 target protein interleukin-1
      receptor-associated kinase-1, and have increased NFkappaB transcriptional
      activity. We hypothesize that PS2 impacts microglial responses through modulation
      of miR146a. PS2 dysfunction, through aging or mutation, may contribute to
      neurodegeneration by influencing the pro-inflammatory behavior of microglia.
      Presenilin 2 (PS2), a membrane associated protease, has been implicated in the
      pathogenesis of Alzheimer disease. We have previously shown that PS2 plays an
      important role in curbing the proinflammatory response in microglia. Here, we
      report the novel finding that PS2 participates in maintaining the basal and
      cytokine induced expression of the innate immunity regulating microRNA, miR146.
      These data suggest one mechanism by which PS2 works to reign in proinflammatory
      microglial behavior and that PS2 dysfunction or deficiency could thus result in
      unchecked proinflammatory activation contributing to neurodegeneration.

PMID- 23952004
TI  - Shaping development through mechanical strain: the transcriptional basis of diet
      induced phenotypic plasticity in a cichlid fish.
AB  - Adaptive phenotypic plasticity, the ability of an organism to change its
      phenotype to match local environments, is increasingly recognized for its
      contribution to evolution. However, few empirical studies have explored the
      molecular basis of plastic traits. The East African cichlid fish Astatoreochromis
      alluaudi displays adaptive phenotypic plasticity in its pharyngeal jaw apparatus,
      a structure that is widely seen as an evolutionary key innovation that has
      contributed to the remarkable diversity of cichlid fishes. It has previously been
      shown that in response to different diets, the pharyngeal jaws change their size,
      shape and dentition: hard diets induce an adaptive robust molariform tooth
      phenotype with short jaws and strong internal bone structures, while soft diets
      induce a gracile papilliform tooth phenotype with elongated jaws and slender
      internal bone structures. To gain insight into the molecular underpinnings of
      these adaptations and enable future investigations of the role that phenotypic
      plasticity plays during the formation of adaptive radiations, the transcriptomes
      of the two divergent jaw phenotypes were examined. Our study identified a total
      of 187 genes whose expression differs in response to hard and soft diets,
      including immediate early genes, extracellular matrix genes and inflammatory
      factors. Transcriptome results are interpreted in light of expression of
      candidate genes-markers for tooth size and shape, bone cells and mechanically
      sensitive pathways. This study opens up new avenues of research at new levels of
      biological organization into the roles of phenotypic plasticity during speciation
      and radiation of cichlid fishes. 

PMID- 23952005
TI  - Microelectrode recording and deep brain stimulation.

PMID- 23952006
TI  - Editor's selection: this month's highlighted articles.

PMID- 23952007
TI  - Prehospital peripheral intravenous vascular access success rates in children.
AB  - OBJECTIVE: Achieving successful peripheral intravenous (PIV) vascular access in
      children can be difficult. In the prehospital setting, opportunities are rare.
      Obtaining access becomes vital in emergent and life-threating conditions, such as
      seizures, hypoglycemia, and cardiac arrest. This study examines prehospital
      pediatric PIV attempts, success rates, and the impact of patient age. METHODS:
      This was a retrospective chart review of patients aged 18 years or younger
      receiving prehospital PIV attempts from January 1, 2003, through May 31, 2011.
      Included cases were identified by querying electronic patient care reports for
      PIV attempts within the specified age range. The documentation of PIV attempts
      and successes was reported by emergency medical service providers. This study was
      approved by an institutional review board. RESULTS: Throughout the 101-month
      study period, there were 261,008 ambulance responses. PIV attempts were made in
      4188 patients aged 18 years or younger. PIV placement was successful in 3699
      patients (88.3%) and failed in 489 (11.7%). Age was significantly associated with
      success. Each 1-year increase in age was associated with an 11% increase in odds
      of PIV success (odds ratio, 1.11; 95% CI, 1.09-1.12; p < 0.001). Success was
      lowest in patients younger than 2 years old, with an overall success rate of
      64.1% (141/220). Accounting for multiple attempts, success was achieved in 53.0%
      of attempts (141/266). CONCLUSIONS: Prehospital PIV attempts are uncommon (2% of
      emergent responses). Success rates are significantly associated with patient age
      in the pediatric population and lowest in those aged 2 years or less.
      Consideration of alternative forms of vascular access in this population may be
      beneficial.

PMID- 23952008
TI  - A rare presentation of neurosyphilis mimicking a unilateral Adie's tonic pupil.
AB  - We describe a case of a female patient who presented with anisocoria and was
      initially diagnosed with a right acute Adie's pupil on the basis of a right tonic
      pupil with absent oculomotor or neurological findings and hyper-responsiveness to
      dilute Pilocarpine. Two months later, the patient returned with bilateral tonic
      pupils and limitation of extraocular movement in the right eye. Subsequent
      laboratory testing revealed neurosyphilis. Our case, only the second ever
      reported, emphasizes the importance of considering the diagnosis of neurosyphilis
      in patients presenting with an isolated acute tonic pupil.

PMID- 23952009
TI  - Optic nerve sheath meningioma: a case report with 15-year follow-up.
AB  - Meningiomas are benign neoplastic lesions of arachnoidal cells of the meninges.
      These tumors may arise wherever meninges exists, such as in the nasal cavity,
      paranasal sinuses, middle ear, and mediastinum. Optic nerve sheath meningiomas
      (ONSMs) are usually unilateral and occur predominantly in middle-aged females,
      although they may be present at any age. We present a case of a 55-year-old
      female with ONSM diagnosed when she was 40 years old. Diagnosis and follow-up was
      based on the clinical picture, CT orbit scan, and magnetic resonance imaging.

PMID- 23952010
TI  - Three-dimensional elemental mapping at the atomic scale in bimetallic
      nanocrystals.
AB  - A thorough understanding of the three-dimensional (3D) atomic structure and
      composition of core-shell nanostructures is indispensable to obtain a deeper
      insight on their physical behavior. Such 3D information can be reconstructed from
      two-dimensional (2D) projection images using electron tomography. Recently,
      different electron tomography techniques have enabled the 3D characterization of
      a variety of nanostructures down to the atomic level. However, these methods have
      all focused on the investigation of nanomaterials containing only one type of
      chemical element. Here, we combine statistical parameter estimation theory with
      compressive sensing based tomography to determine the positions and atom type of
      each atom in heteronanostructures. The approach is applied here to investigate
      the interface in core-shell Au@Ag nanorods but it is of great interest in the
      investigation of a broad range of nanostructures. 

PMID- 23952011
TI  - Favourable prognostic role of regression of primary melanoma in AJCC stage I-II
      patients.
AB  - BACKGROUND: The prognostic significance of regression in primary melanoma has
      been debated over the past few years. Once it was considered to be a negative
      prognostic factor, as it may have prevented proper melanoma thickness
      measurement, therefore affecting the staging of the tumours. For this reason, it
      was considered to be an indication for sentinel lymph node biopsy (SLNB) in
      melanoma < 1 mm. OBJECTIVES: To ascertain the utility of SLNB in thin melanoma
      and to clarify the role of regression in disease-free survival (DFS) and overall
      survival (OS) in our series. METHODS: We analysed data collected from 1693
      consecutive patients with AJCC (American Joint Committee on Cancer) stage I-II
      melanoma. RESULTS: Globally, SLNB was performed in 656 out of 1693 patients.
      Regression was present in 349 patients and 223 of them were characterized by thin
      lesions. SLNB was performed in 104 cases of thin melanoma with regression. The
      majority of regional lymph node metastases were observed in patients who did not
      undergo SLNB (89 out of 132). Among the remaining 43 'false negative' patients
      only three showed regression in the primary. Using the Cox multivariate model,
      histological regression maintained a significant protective role [hazard ratio
      (HR) 0.62, P = 0.012 for DFS; HR 0.43, P = 0.008 for OS] when corrected for the
      principal histopathological and clinical features, despite SLNB. CONCLUSIONS: We
      confirmed that regression alone should not be a reason to perform SLNB in thin
      melanoma and, on the contrary, it can be considered a favourable prognostic
      factor in patients with AJCC stage I-II melanoma.

PMID- 23952012
TI  - Expression of antimicrobial peptides and toll-like receptors is increased in
      tinea and pityriasis versicolor.
AB  - In superficial tinea and pityriasis versicolor, the causative fungi are for the
      most part confined to the stratum corneum which is barely reached by leukocytes.
      Therefore, a role of non-cellular components in the epidermal antifungal defence
      was suggested. To investigate the presence of such factors in these infections,
      the expression of human beta defensins 2 and 3 (hBD-2, hBD-3), RNase 7,
      psoriasin, toll-like receptors 2, 4 and 9 (TLR2, TLR4 and TLR9) and dectin 2 was
      analysed by use of immunostainings in skin biopsies. We found that hBD2, hBD3,
      psoriasin, RNase7, TLR2 and TLR4 were significantly more often expressed in
      distinct layers of lesional epidermis as compared with uninfected epidermis. In
      both infections but not in normal skin, hBD2 and hBD3 were commonly expressed
      within the stratum corneum and in the stratum granulosum. Similarly, psoriasin
      was seen more often in the upper skin layers of both infections as compared with
      normal skin. No significant differences between normal and infected skin were
      found for the expression of TLR9 and dectin 2. Our findings clearly show the
      expression of specific antimicrobial proteins and defence-related ligands in
      superficial tinea as well as in pityriasis versicolor, suggesting that these
      factors contribute to fungal containment. 

PMID- 23952014
TI  - Response to Marinelli and Marchissio.

PMID- 23952016
TI  - Detection of carriers in the Ashkenazi Jewish population: an objective comparison
      of high-throughput genotyping versus gene-by-gene testing.
AB  - BACKGROUND: High-throughput genotyping allows rapid identification of targeted
      mutations at a fraction of the cost of current gene-by-gene testing
      methodologies. An objective comparison of the two methodologies allows providers
      to assess the clinical validity/utility of high-throughput carrier screening and
      establish a comfort level with new genomic technologies. AIM: To verify that high
      throughput genotyping accurately determines patient carrier status, DNA samples
      from previously identified carriers (n=31) of Ashkenazi Jewish genetic diseases
      were anonymized and submitted for retesting by high-throughput genotyping.
      RESULTS: The results were 100% concordant (95% CI: 0.998-1), demonstrating that
      high-throughput genotyping assays accurately identify carriers of targeted
      mutations in the Ashkenazi Jewish population. In addition, carrier status for
      diseases and mutations not previously tested was uncovered using the high
      throughput assay. CONCLUSIONS: High-throughput genotyping is a cost-effective and
      clinically valid approach to carrier screening. The use of a broader screen for
      Ashkenazi Jewish individuals increases the detection of carriers in this
      population.

PMID- 23952017
TI  - Production of recombinant capsid protein of Macrobrachium rosenbergii nodavirus
      (r-MCP43) of giant freshwater prawn, M. rosenbergii (de Man) for immunological
      diagnostic methods.
AB  - White tail disease (WTD) caused by Macrobrachium rosenbergii nodavirus (MrNV) and
      extra small virus (XSV) is a serious problem in prawn hatcheries. The gene for
      capsid protein of MrNV (MCP43) was cloned into pRSET B expression vector. The
      MCP43 protein was expressed as a protein with a 6-histidine tag in Escherichia
      coli GJ1158 with NaCl induction. This recombinant protein, which was used to
      raise the antiserum in rabbits, recognized capsid protein in different WTD
      infected post-larvae and adult prawn. Various immunological methods such as
      Western blot, dot blot and ELISA techniques were employed to detect MrNV in
      infected samples using the antiserum raised against recombinant MCP43 of MrNV.
      The dot blot assay using anti-rMCP43 was found to be capable of detecting MrNV in
      WTD-infected post-larvae as early as at 24 h post-infection. The antiserum raised
      against r-MCP43 could detect the MrNV in the infected samples at the level of 100
      pg of total protein. The capsid protein of MrNV estimated by ELISA using anti
      rMCP43 and pure r-MCP43 as a standard was found to increase gradually during the
      course of infection from 24 h p.i. to moribund stage. The results of
      immunological diagnostic methods employed in this study were compared with that
      of RT-PCR to test the efficiency of antiserum raised against r-MCP43 for the
      detection of MrNV. The Western blot, dot blot and ELISA detected all MrNV
      positive coded samples as detected by RT-PCR.

PMID- 23952018
TI  - Pedobarographic evaluation of body weight distribution on the lower limbs and
      balance after derotation corticotomies using the Ilizarov method.
AB  - Distortion of the axis and shortening of the limbs result in multiple
      musculoskeletal pathologies. Rotation disorders should also be included among the
      disorders of the axis of the lower limb. In the case of rotational distortion,
      only derotation osteotomy can effectively correct torsion-associated
      deformations. Rotational distortion correction is accompanied by translational
      displacement and torsion, which results in more complex biomechanics. Using the
      pedobarographic platform, it is possible to evaluate static and dynamic posture
      and gait, percentage of body weight distribution on the lower limbs, and balance.
      Physiological gait and distribution of weight on the lower extremities are
      symmetrical. Balance is one of the determinants of proper biomechanics of the
      musculoskeletal system. An important aspect of treatment evaluation is
      pedobarographic assessment of balance and body weight distribution on the lower
      extremities ratio. The aim of this work was to evaluate the pedobarographic
      assessment of body weight distribution on the lower limbs and balance in patients
      with derotation corticotomies using the Ilizarov method. The study examined a
      group of 56 patients, who underwent derotation corticotomy using the Illizarov
      method between 1996 and 2012 at the Clinic of Orthopaedics and Traumatology of
      the Musculoskeletal System in Wroclaw. The control group consisted of 54
      patients, who were treated with correctional derotation-free corticotomy using
      the Ilizarov. Distribution of body weight on the lower limbs and balance were
      assessed with the pedobarographic platform. Following derotation corticotomy, the
      amount of body weight placed on the operated limb by subjects from the study
      group averaged 47.81%, 52.19% in the case of the healthy limb. These differences
      were not statistically significant. The difference between the average percentage
      of body weight placed on the diseased and healthy limb in the study group and the
      controls were not found to be statistically significant. There were no
      statistical differences in the average length of the gravity line or in the
      average surface area of the center of gravity position between the study and
      control groups. Balanced distribution of body weight on the lower limbs was
      achieved following derotation corticotomies using the Ilizarov method. Derotation
      corticotomies performed with the Ilizarov method allow for achieving
      normalization of body weight distribution on the lower limbs and balance, with
      values similar to those resulting from Ilizarov method derotation-free osteotomy.

PMID- 23952019
TI  - CHF5074 Reduces Biomarkers of Neuroinflammation in Patients with Mild Cognitive
      Impairment: A 12-Week, Double-Blind, Placebo-Controlled Study.
AB  - As neuroinflammation is an early event in the pathogenesis of Alzheimer's
      disease, new selective anti-inflammatory drugs could lead to promising preventive
      strategies. We evaluated the safety, tolerability, pharmacokinetics and
      pharmacodynamics of CHF5074, a new microglial modulator, in a 12-week, double
      blind, placebo-controlled, parallel groups, ascending dose study involving 96 MCI
      patients. Subjects were allocated into three successive study cohorts to receive
      ascending, titrated doses of CHF5074 (200, 400 or 600 mg/day) or placebo. Vital
      signs, cardiac safety, neuropsychological performance and safety clinical
      laboratory parameters were assessed on all subjects. Plasma samples were
      collected throughout the study for measuring drug concentrations, soluble CD40
      ligand (sCD40L) and TNF-alpha. At the end of treatment, cerebrospinal fluid (CSF)
      samples were optionally collected after the last dose to measure drug levels,
      beta-amyloid1-42 (Abeta42), tau, phospho-tau181, sCD40L and TNF-alpha. Ten
      patients did not complete the study: one in the placebo group (consent
      withdrawn), two in the 200-mg/day treatment group (consent withdrawn and unable
      to comply) and seven in the 400-mg/day treatment group (five AEs, one consent
      withdrawn and one unable to comply). The most frequent treatment-emergent adverse
      events were diarrhea, dizziness and back pain. There were no clinically
      significant treatment-related clinical laboratory, vital sign or ECG
      abnormalities. CHF5074 total body clearance depended by gender, age and
      glomerular filtration rate. CHF5074 CSF concentrations increased in a dose
      dependent manner. At the end of treatment, mean sCD40L and TNF-alpha levels in
      CSF were found to be inversely related to the CHF5074 dose (p=0.037 and p=0.001,
      respectively). Plasma levels of sCD40L in the 600-mg/day group were significantly
      lower than those measured in the placebo group (p=0.010). No significant
      differences between treatment groups were found in neuropsychological tests but a
      positive dose-response trend was found on executive function in APOE4 carriers.
      This study shows that CHF5074 is well tolerated in MCI patients after a 12-week
      titrated treatment up to 600 mg/day and dose-dependently affects central nervous
      system biomarkers of neuroinflammation.

PMID- 23952020
TI  - Interprofessional collaboration: issues for practice and research.
AB  - SUMMARY The current health care system is based on accountability, cost
      containment, and quality of care. Collaborative practice models may be a viable
      means for improving health care delivery. The purpose of this paper is to outline
      how interprofessional education, practice, and research can establish economic
      benefits and effective clinical outcomes outside of discipline specific
      investigation. 

PMID- 23952021
TI  - The rural elderly assessment project: a model for interdisciplinary team
      training.
AB  - SUMMARY The Rural Elderly Assessment Project (REAP) was designed to train
      occupational therapy, physical therapy, physician assistant, and public health
      faculty and students to conduct interdisciplinary team health assessments with
      rural, community-dwelling older adults. This article highlights key features of
      the project's design and implementation and presents preliminary evaluation data
      from the 25 students who participated in the project. Students completed several
      pre- and post-test measures. Statistically significant improvements were observed
      in all but one of the knowledge, skill, and attitude domains that were
      specifically targeted by the project. Students identified a variety of benefits
      they received from participating in the project, and all students indicated that
      they would recommend the project to another student. Implications for project
      replication and interdisciplinary team training of allied health students are
      discussed. 

PMID- 23952022
TI  - Physical therapy and occupational therapy: partners in rehabilitation for persons
      with movement impairments.
AB  - SUMMARY The professions of physical therapy and occupational therapy have
      legitimate roles in the restoration of human movement in the rehabilitation
      process. This paper first presents a physical therapy perspective on changing
      trends in therapeutic exercise. Recent trends in physical therapy reflect a shift
      away from isolating patterns of movement and open kinetic chain exercises toward
      a new emphasis on functional patterns of movement and closed kinetic chain
      exercises. Rehabilitation of persons with hip fracture is used as an example of
      these shifting trends. Next, the paper presents an occupational therapy
      perspective. Occupational therapy's historical emphasis on the use of
      naturalistic occupations as the context for therapeutic exercise is described.
      Theoretical advantages of occupationally embedded movement are listed, and recent
      research in support of naturalistic occupations is summarized. Physical therapy
      and occupational therapy are distinct professions with autonomous outlooks and
      terminologies, but the responsibilities of physical therapists and occupational
      therapists potentially overlap in the restoration of movement. Suggestions are
      made for interdisciplinary teamwork whereby the holistically considered welfare
      of the patient is always the primary concern of all therapists. 

PMID- 23952023
TI  - Dementia, nutrition, and self-feeding: a systematic review of the literature.
AB  - SUMMARY The outcomes of feeding training are typically evaluated in terms of
      feeding skills and swallowing abilities rather than the ultimate goal of feeding,
      namely, adequate nutritional status. To increase occupational therapy
      practitioners' awareness of nutritional status as an outcome of feeding training,
      a systematic review of the research literature was conducted to examine the
      relationship between nutritional status and self-feeding skills in people with
      dementia. Studies were evaluated by the strength of their evidence and analyzed
      to determine the relationships among dementia, nutritional status, and the
      ability to feed one's self. Results revealed that although nutritional status in
      people with dementia is variable, there is a tendency for lower body weight,
      lower measures of body composition, and lower body mass indexes in persons with
      dementia compared to those with no cognitive impairment. Individuals who feed
      themselves tend to weigh more compared to those who need assistance for feeding.
      There is also evidence to support that as feeding status improves or declines,
      body weight similarly increases or decreases. 

PMID- 23952024
TI  - Promoting awareness and understanding of occupational therapy and physical
      therapy in young school aged children: an interdisciplinary approach.
AB  - SUMMARY Public awareness and understanding of the professions of occupational
      therapy and physical therapy are limited. In this study, we examined perceptions
      of young school-aged children about occupational therapy and physical therapy as
      part of a larger grant project funded by the National Institute on Drug Abuse
      (R25 DA 12168 and R25 DA13522). One hundred three elementary school children (55
      boys and 48 girls), grades 3 to 7, from local schools attended a one-day
      neuroscience and allied health profession exposition held at a local Boys & Girls
      Club. Children's understanding of occupational therapy and physical therapy was
      assessed through a pre/post questionnaire prior to and immediately after
      attending the exposition. At five of the 18 exhibition booths, faculty members
      and students from occupational therapy and physical therapy introduced and
      explained what occupational and physical therapists do at their work through
      interactive demonstrations. The results of the current study revealed that prior
      to attending the exposition, children's understanding of occupational therapy and
      physical therapy was limited. On pre-test, children reported they have some
      understanding of occupational therapy (18.6%) and physical therapy (34.9%).
      Children's understanding of occupational therapy and physical therapy, however,
      dramatically increased after the exposition (75.6% vs. 18.6%, 98.9% vs. 34.9%,
      respectively). Furthermore, the scope and depth of children's understanding also
      improved considerably. This finding suggests that an interactive neuroscience
      exposition including occupational therapy and physical therapy is an effective
      way to promote children's awareness and understanding of the professions.
      Implications for practice and future research directions are discussed in the
      study. 

PMID- 23952025
TI  - Collaboration between team members in inclusive educational settings.
AB  - SUMMARY The inclusion of students with disabilities into general education
      settings and programs has necessitated the development of integrated,
      collaborative service delivery models that are compatible with the goals and
      purpose of inclusive education. Although there is considerable theoretical
      literature on collaboration, there is minimal empirical data available on the
      process or its outcomes. The purpose of this exploratory study was to gain
      insight on the perspectives of regular and special educators, and occupational,
      physical, and speech-language therapists towards collaboration. Using a semi
      structured interview, participants (n = 51) responded to questions concerning the
      definition, nature, and extent of collaboration in their school setting.
      Participants also responded to questions related to the advantages of, barriers
      towards, and strategies to promote collaboration. Participants typically defined
      collaboration as not a problem-solving process, but in terms of activities
      associated with it. Results indicate that participants believed collaboration was
      mutually beneficial for both students and team members. However, implementing a
      collaborative approach was problematic. Lack of administrative approval for time
      for planning meetings was the most frequently cited barrier to collaboration.
      Although 51.6% of the participants reported time available for collaborative
      planning by regular and special educators, only 21.5% of the participants
      reported this time being available for therapists to meet with educators.
      Education about collaboration, either in professional/preservice education
      programs or as continuing education, was recommended as a strategy to facilitate
      a collaborative approach. Although a collaborative approach is being used by
      therapists and educators more and more frequently, there is a need for research
      to validate its efficacy. 

PMID- 23952026
TI  - A response to traumatized children: developing a best practices model.
AB  - SUMMARY This manuscript describes the key components for establishing
      collaborative partnerships in the delivery of services to children who have been
      traumatized by abuse, neglect, and prenatal exposure to alcohol. Specifically,
      the manuscript addresses: the national need for such collaborative partnerships;
      the effects of abuse, neglect, and prenatal exposure to alcohol on developmental
      and educational outcomes; the process used to develop the children's trauma
      assessment center (CTAC) including discussion on the family centered and
      transdisciplinary nature of the center; and the accomplishment and future goals
      of CTAC. The members of the CTAC team currently include the disciplines of
      counseling, occupational therapy, pediatric medicine, social work, and speech
      language pathology. Future goals include expanding the core team to include the
      nursing and educational psychology disciplines. 

PMID- 23952028
TI  - The marionette technique for treatment of isolated fourth ventricle: technical
      note.
AB  - Isolated fourth ventricle is not uncommon in complex posthemorrhagic or
      postinfectious hydrocephalus. When the condition is symptomatic, the current
      surgical treatment is endoscopic aqueductoplasty, followed by endoscope-assisted
      placement of a catheter in the fourth ventricle. The authors suggest a very
      simple method of steering the tip of standard ventricular catheters by using
      materials commonly available in all operating rooms. The main advantage of this
      method is that it permits less invasive transaqueductal drainage of trapped
      fourth ventricles, especially in cases of narrow third ventricle, because the
      scope and catheter are introduced in sequence and not in a double-barreled
      fashion. Two illustrative cases are reported. 

PMID- 23952029
TI  - Medulloblastoma invading the transverse sinus: case report.
AB  - Medulloblastoma is a highly malignant brain tumor of childhood. Although
      craniospinal dissemination within the subarachnoid space is common, invasion of
      the dural sinuses is rare. Here, the authors report on a 15-year-old girl who
      presented with a right cerebellar mass, obstructive hydrocephalus, and
      radiographic evidence of tumor invasion into the right transverse-sigmoid sinus
      junction. The patient underwent posterior fossa craniotomy, gross-total resection
      of the intraparenchymal component of the right cerebellar tumor, and coagulation
      of the tumor invading the transverse sinus. After pathological confirmation of
      anaplastic medulloblastoma, the patient underwent craniospinal radiation therapy
      and high-dose chemotherapy. At 2 years posttreatment, the child was
      neurologically intact with no radiographic evidence of residual disease or
      recurrence. The implications for disease prognosis and management are discussed. 

PMID- 23952030
TI  - "Horseshoe cord terminus" sans filum around a bone spur: a rare composite of
      faulty gastrulation with agenesis of secondary neurulation: case report.
AB  - Split cord malformation (SCM) is classified based on the presence of a bone spur
      and double dural sac. The authors report on a 6-year-old child with primary
      enuresis in whom MRI findings were suggestive of Type I SCM, and who had unique
      intraoperative findings of a horseshoe-shaped split cord terminus anchored by a
      bone spur without the normally tapering conus and filum. The typical appearance
      of cauda equina was absent, with all the roots arising from the horseshoe cord
      terminus. This composite anomaly is probably due to the rare combination of
      faulty gastrulation with abnormal persistence of endomesenchymal tract causing
      SCM, with concurrent agenesis of secondary neurulation in turn causing absence of
      filum. 

PMID- 23952031
TI  - Bilateral subthalamic nucleus deep brain stimulation for refractory total body
      dystonia secondary to metabolic autopallidotomy in a 4-year-old boy with
      infantile methylmalonic acidemia: case report.
AB  - The methylmalonic acidemias (MMAs) are a group of inborn errors of metabolism
      resulting in the accumulation of methylmalonic acid in body tissues and fluids. A
      recognized complication of MMA is bilateral liquefaction of the globus pallidi,
      resulting in a fulminant total body dystonia of childhood often refractory to
      medical treatment. This case of total body dystonia due to MMA in a 4-year-old
      boy had been medically refractory for 15 months. Complete metabolic destructive
      liquefaction of the pallidi, that is, autopallidotomy, necessitated an
      alternative, bilateral subthalamic nucleus (STN) target for deep brain
      stimulation (DBS) with a marked improvement in dystonia and reduction in pain.
      The case illustrates the efficacy of STN DBS in this condition and the technical
      challenges in targeting the STN in a small child. 

PMID- 23952032
TI  - Letter to the editor: Hemangiomas and propranolol.

PMID- 23952033
TI  - Letter to the Editor: Endoscope-assisted multisuturectomy for scaphocephaly.

PMID- 23952034
TI  - Macular pucker in association with RPE adenoma: a report of a case and review of
      the literature.
AB  - BACKGROUND: Retinal pigment epithelium (RPE) adenoma is an extremely rare tumor
      of the posterior segment which must be differentiated from other choroidal
      tumors, such as choroidal nevus or melanoma. We report the case of a patient with
      RPE adenoma coincident with macular pucker who underwent successful pars plana
      vitrectomy and membrane peeling. PATIENT AND METHODS: A 58-year-old female
      patient was diagnosed with RPE adenoma and epiretinal membrane and subsequently
      underwent pars plana vitrectomy and epiretinal membrane peeling. RESULTS: RPE
      adenoma was diagnosed and, following vitrectomy with membrane peeling vision,
      improved to 20/20 with resolution of symptoms of distortion. Sixteen months of
      follow-up revealed no clinical change in the RPE adenoma and stable vision.
      CONCLUSION: The diagnosis of RPE adenoma can be made upon consideration of unique
      clinical characteristics of these benign tumors. RPE adenoma may be more closely
      associated with epiretinal membrane than previously believed, given recent
      advances in imaging technology. We describe our management strategy, which
      included observation of the adenoma and surgical removal of the epiretinal
      membrane.

PMID- 23952035
TI  - Phacoemulsification in a Rare Case of Alport's Syndrome.
AB  - AIM: To report a rare case of Alport Syndrome (AS) highlighting the precautions
      and surgical complications during phacoemulsification. METHOD: A 35 year old
      female presented with bilateral painless progressive diminution of vision since 6
      months and had bilateral deafness since 12 years. Best corrected visual acuity
      (BCVA) in both the eyes was 4/60. Bilateral anterior lenticonus, posterior polar
      cataract with posterior lenticonus, macular and peripheral retinal flecks, which
      are rarely reported in females, were present. Right eye phacoemulsification and
      IOL implantation was done. RESULT: During surgery capsulorrhexis underwent
      multiple dehiscence in a "flower petal pattern" due to fragile capsule. It was
      completed with microforceps under high viscocity viscoelastic. IOL was placed in
      sulcus due to extension of capsulorrhexis. BCVA was 6/12 at 1 month. CONCLUSION:
      This rare case highlights the importance of an eye ailment in revealing an
      important systemic disease. It also highlights proper management of complications
      that can give good result even in difficult cases.

PMID- 23952036
TI  - Outcome prediction in traumatic brain injury.

PMID- 23952037
TI  - Ejaculation-preserving transurethral resection of prostate and bladder neck:
      short- and long-term results of a new innovative resection technique.
AB  - INTRODUCTION: Loss of antegrade ejaculation is a risk with conventional resection
      of the prostate (transurethral resection of the prostate [TURP]). The aim of this
      study was to determine the short- and long-term preservation of antegrade
      ejaculation and functional results with the novel ejaculation-preserving TURP
      (epTURP). PATIENTS AND METHODS: Prospective evaluation of 89 consecutive patients
      with bladder outlet obstructions aged 27 to 78 years, enrolled from June 2001 to
      January 2005. Endpoints were change in objective (uroflowmetry, postvoid residual
      [PVR]), and subjective (International Prostate Symptoms Score [IPSS], Life
      Quality Index [LQI]; International Index of Erectile Function-5 [IIEF-5+] with
      two additional questions) measures of function. All patients received follow-up
      examinations at 3 and >=60 months. RESULTS: Overall, 87 and 63 patients were
      evaluated after 3 and 60 months, respectively. Antegrade ejaculation was
      preserved in 79 of 87 (90.8%) patients at 3 months. Significant improvements in
      maximum flow rate (+14.3 mL/s), micturition volume (+71.6 mL), and PVR (-59 mL;
      p<=0.002 for all) were observed at 3 months. Micturition symptoms, as measured by
      IPSS and LQI, were also significantly reduced (mean change of 18.3 and 2.9,
      respectively; p<0.001). Improvements were maintained at 60 months. No serious
      adverse events were reported. Eight (12.7%) patients received a second epTURP due
      to the development of bladder neck scar tissue during long-term follow-up.
      CONCLUSION: Antegrade ejaculation was preserved with the use of epTURP with
      excellent outcome. Observed symptomatic and functional outcomes were comparable
      with conventional TURP. The results from this study underline the necessity of
      reviewing the old concept of ejaculation physiology.

PMID- 23952038
TI  - Mild dehydration and cycling performance during 5-kilometer hill climbing.
AB  - CONTEXT: Hydration has been shown to be an important factor in performance;
      however, the effects of mild dehydration during intense cycling are not clear.
      OBJECTIVE: To determine the influence of mild dehydration on cycling performance
      during an outdoor climbing trial in the heat (ambient temperature = 29.0 degrees
      C +/- 2.2 degrees C). DESIGN: Crossover study. SETTING: Outdoor. PATIENTS OR
      OTHER PARTICIPANTS: Ten well-trained, male endurance cyclists (age = 28 +/- 5
      years, height = 182 +/- 0.4 cm, mass = 73 +/- 4 kg, maximal oxygen uptake = 56 +/
      9 mL.min(-1).kg(-1), body fat = 23% +/- 2%, maximal power = 354 +/- 48 W).
      INTERVENTION(S): Participants completed 1 hour of steady-state cycling with or
      without drinking to achieve the desired pre-exercise hydration level before 5-km
      hill-climbing cycling. Participants started the 5-km ride either euhydrated (EUH)
      or dehydrated by -1% of body mass (DEH). MAIN OUTCOME MEASURE(S): Performance
      time, core temperature, sweat rate, sweat sensitivity, and rating of perceived
      exertion (RPE). RESULTS: Participants completed the 5-km ride 5.8% faster in the
      EUH (16.6 +/- 2.3 minutes) than DEH (17.6 +/- 2.9 minutes) trial (t1 = 10.221, P
      = .001). Postexercise body mass was -1.4% +/- 0.3% for the EUH trial and -2.2% +/
      0.2% for the DEH trial (t1 = 191.384, P < .001). Core temperature after the
      climb was greater during the DEH (39.2 degrees C +/- 0.3 degrees C) than EUH
      (38.8 degrees C +/- 0.2 degrees C) trial (t1 = 8.04, P = .005). Sweat rate was
      lower during the DEH (0.44 +/- 0.16 mg.m(-2).s(-1)) than EUH (0.51 +/- 0.16 mg.m(
      2).s(-1)) trial (t8 = 2.703, P = .03). Sweat sensitivity was lower during the DEH
      (72.6 +/- 32 g. degrees C(-1).min(-1)) than EUH (102.6 +/- 54.2 g. degrees C(
      1).min(-1)) trial (t8 = 3.072, P = .02). Lastly, RPE after the exercise
      performance test was higher for the DEH (19.0 +/- 1.0) than EUH (17.0 +/- 1.0)
      participants (t9 = -3.36, P = .008). CONCLUSIONS: We found mild dehydration
      decreased cycling performance during a 5-km outdoor hill course, probably due to
      greater heat strain and greater perceived intensity.

PMID- 23952039
TI  - Ad libitum fluid intake and plasma responses after pickle juice, hypertonic
      saline, or deionized water ingestion.
AB  - CONTEXT: Adding sodium (Na(+)) to drinks improves rehydration and ad libitum
      fluid consumption. Clinicians (~25%) use pickle juice (PJ) to treat cramping.
      Scientists warn against PJ ingestion, fearing it will cause rapid plasma volume
      restoration and thereby decrease thirst and delay rehydration. Advice about
      drinking PJ has been developed but never tested. OBJECTIVE: To determine if
      drinking small volumes of PJ, hypertonic saline (HS), or deionized water (DIW)
      affects ad libitum DIW ingestion, plasma variables, or perceptual indicators.
      DESIGN: Crossover study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS:
      Fifteen, euhydrated (urine specific gravity <= 1.01) men (age = 22 +/- 2 years,
      height = 178 +/- 6 cm, mass = 82.9 +/- 8.4 kg). INTERVENTION(S): Participants
      completed 3 testing days (>= 72 hours between days). After a 30-minute rest, a
      blood sample was collected. Participants completed 60 minutes of hard exercise
      (temperature = 36 +/- 2 degrees C, relative humidity = 16 +/- 1%). Postexercise,
      they rested for 30 minutes; had a blood sample collected; rated thirst, fullness,
      and nausea; and ingested 83 +/- 8 mL of PJ, HS, or DIW. They rated drink
      palatability (100-mm visual analog scale) and were allowed to drink DIW ad
      libitum for 60 minutes. Blood samples and thirst, fullness, and nausea ratings
      (100-mm visual analog scales) were collected at 15, 30, 45, and 60 minutes
      posttreatment drink ingestion. MAIN OUTCOME MEASURE(S): Ad libitum DIW volume,
      percentage change in plasma volume, plasma osmolality (OSMp,) plasma sodium
      concentration ([Na(+)]p), and thirst, fullness, nausea, and palatability ratings.
      RESULTS: Participants consumed more DIW ad libitum after HS (708.03 +/- 371.03
      mL) than after DIW (532.99 +/- 337.14 mL, P < .05). Ad libitum DIW ingested after
      PJ (700.35 +/- 366.15 mL) was similar to that after HS and DIW (P > .05). Plasma
      sodium concentration, OSMp, percentage change in plasma volume, thirst, fullness,
      and nausea did not differ among treatment drinks over time (P > .05). Deionized
      water (73 +/- 14 mm) was more palatable than HS (17 +/- 13 mm) or PJ (26 +/- 16
      mm, P < .05). CONCLUSIONS: The rationale behind advice about drinking PJ is
      questionable. Participants drank more, not less, after PJ ingestion, and plasma
      variables and perceptual indicators were similar after PJ and DIW ingestion.
      Pickle juice did not inhibit short-term rehydration.

PMID- 23952040
TI  - Differences in lateral drop jumps from an unknown height among individuals with
      functional ankle instability.
AB  - CONTEXT: Functional ankle instability (FAI) is a debilitating condition that has
      been reported to occur after 20% to 50% of all ankle sprains. Landing from a jump
      is one common mechanism of ankle injury, yet few researchers have explored the
      role of visual cues and anticipatory muscle contractions, which may influence
      ankle stability, in lateral jumping maneuvers. OBJECTIVE: To examine muscle
      activation strategies between FAI and stable ankles under a lateral load and to
      evaluate the differences in muscle activation in participants with FAI and
      participants with stable ankles when they were unable to anticipate the onset of
      lateral loads during eyes-open versus eyes-closed conditions. DESIGN: Case
      control study. SETTING: Controlled laboratory setting. PATIENTS OR OTHER
      PARTICIPANTS: A total of 40 people participated: 20 with FAI and 20 healthy,
      uninjured, sex- and age-matched persons (control group). INTERVENTION(S):
      Participants performed a 2-legged lateral jump off a platform onto a force plate
      set to heights of 35 cm or 50 cm and then immediately jumped for maximal height.
      They performed jumps in 2 conditions (eyes open, eyes closed) and were unaware of
      the jump height when their eyes were closed. MAIN OUTCOME MEASURE(S): Amplitude
      normalized electromyographic (EMG) area (%), peak (%), and time to peak in the
      tibialis anterior (TA), peroneus longus (PL), and lateral gastrocnemius (LG)
      muscles were measured. RESULTS: Regardless of the eyes-open or eyes-closed
      condition, participants with FAI had less preparatory TA (t158 = 2.22, P = .03)
      and PL (t158 = 2.09, P = .04) EMG area and TA (t158 = 2.45, P = .02) and PL (t158
      = 2.17, P = .03) peak EMG than control-group participants. CONCLUSIONS: By
      removing visual cues, unanticipated lateral joint loads occurred simultaneously
      with decreased muscle activity, which may reduce dynamic restraint capabilities
      in persons with FAI. Regardless of visual impairment and jump height,
      participants with FAI exhibited PL and TA inhibition, which may limit
      talonavicular stability and intensify lateral joint surface compression and pain.

PMID- 23952041
TI  - Exercise intolerance in individuals with postconcussion syndrome.
AB  - CONTEXT: Little is known about exercise intolerance or the utility of an exercise
      evaluation in patients with postconcussion syndrome (PCS). OBJECTIVE: To assess
      exercise intolerance in male and female patients with PCS. DESIGN: Cross
      sectional study. SETTING: Laboratory setting. PATIENTS OR OTHER PARTICIPANTS:
      Participants included a convenience sample of 34 patients with PCS (17 males, 17
      females; age = 25.9 +/- 10.9 years) and 22 uninjured individuals on whom we
      gathered historical deidentified laboratory data (control group; 11 males, 11
      females; age = 23.3 +/- 6.2 years). MAIN OUTCOME MEASURE(S): Self-reported
      symptoms, heart rate, systolic and diastolic blood pressures (BPs), and the Borg
      rating of perceived exertion were measured before, during each minute of, and
      immediately after a graded treadmill exercise test (Balke protocol). Exercise was
      stopped when participants could no longer maintain the effort or reported the
      onset of or increase in PCS symptoms. RESULTS: Exercise test duration (8.5 +/-
      4.4 minutes versus 17.9 +/- 3.6 minutes; t51 = 1.8, P < .001), heart rate (142.8
      +/- 24.1 versus 175.2 +/- 17.4; t54 = -5.5, P < .001), and systolic BP (142.1 +/-
      18.3 mm Hg versus 155.5 +/- 24.5 mm Hg; t53 = 2.3, P = .02) were lower, and
      diastolic BP (78.4 +/- 10.2 mm Hg versus 73.5 +/- 11.7 mm Hg; t53 = 2.2, P = .03)
      was higher at test cessation in the PCS than control group. Cox regression showed
      the odds of a shorter exercise duration were nearly 8 times greater in the PCS
      than control group (hazard ratio = 7.93; 95% confidence interval = 3.39, 18.56).
      In the general linear models that adjusted for differences in test duration,
      rating of perceived exertion was the only physiologic measure to show an overall
      difference between groups, with the control group reporting higher ratings than
      the PCS group (t53 = -6.0, P < .001). Within the PCS group, systolic BP was the
      only measure to show a sex effect, with males showing higher pressure readings
      than females throughout the exercise tests (t31 = 2.8, P = .009). CONCLUSIONS:
      Patients with PCS had a symptom-limited response to exercise, and the treadmill
      test was a potentially useful tool to monitor the recovery from PCS.

PMID- 23952042
TI  - Postfixed brachial plexus radiculopathy due to thoracic disc herniation in a
      collegiate wrestler: a case report.
AB  - OBJECTIVE: To present the unique case of a collegiate wrestler with C7 neurologic
      symptoms due to T1-T2 disc herniation. BACKGROUND: A 23-year-old male collegiate
      wrestler injured his neck in a wrestling tournament match and experienced pain,
      weakness, and numbness in his left upper extremity. He completed that match and 1
      additional match that day with mild symptoms. Evaluation by a certified athletic
      trainer 6 days postinjury showed radiculopathy in the C7 distribution of his left
      upper extremity. He was evaluated further by the team physician, a primary care
      physician, and a neurosurgeon. DIFFERENTIAL DIAGNOSIS: Cervical spine injury,
      stinger/burner, peripheral nerve injury, spinal cord injury, thoracic outlet
      syndrome, brachial plexus radiculopathy. TREATMENT: The patient initially
      underwent nonoperative management with ice, heat, massage, electrical
      stimulation, shortwave diathermy, and nonsteroidal anti-inflammatory drugs
      without symptom resolution. Cervical spine radiographs were negative for bony
      pathologic conditions. Magnetic resonance imaging showed evidence of T1-T2 disc
      herniation. The patient underwent surgery to resolve the symptoms and enable him
      to participate for the remainder of the wrestling season. UNIQUENESS: Whereas
      brachial plexus radiculopathy commonly is seen in collision sports, a postfixed
      brachial plexus in which the T2 nerve root has substantial contribution to the
      innervation of the upper extremity is a rare anatomic variation with which many
      health care providers are unfamiliar. CONCLUSIONS: The injury sustained by the
      wrestler appeared to be C7 radiculopathy due to a brachial plexus traction
      injury. However, it ultimately was diagnosed as radiculopathy due to a T1-T2
      thoracic intervertebral disc herniation causing impingement of a postfixed
      brachial plexus and required surgical intervention. Athletic trainers and
      physicians need to be aware of the anatomic variations of the brachial plexus
      when evaluating and caring for patients with suspected brachial plexus
      radiculopathies.

PMID- 23952043
TI  - Scapular kinematics and shoulder elevation in a traditional push-up.
AB  - CONTEXT: Proper scapulothoracic motion is critical for the health and function of
      the shoulder and represents a principal focus in the rehabilitation setting.
      Variants of the traditional push-up are used frequently to help restore proper
      scapular kinematics. To date, substantial research has focused on muscle
      activation levels of rotator cuff and scapular-stabilizing musculature, whereas a
      dearth of literature exists regarding scapular kinematics during push-up
      variants. OBJECTIVE: To examine the effect of shoulder position on scapular
      kinematics across the range of motion (ROM) of a traditional push-up. DESIGN:
      Cross-sectional study. SETTING: University laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Sixteen healthy participants without a history of upper extremity
      or spine injury requiring rehabilitation or surgery. INTERVENTION(S):
      Participants performed a traditional push-up while kinematic measurements were
      acquired from multiple upper extremity segments. The 3 shoulder position
      conditions were (1) self-selected position, (2) shoulder adducted upon ascent (at
      side), and (3) shoulder elevated to approximately 90 degrees . MAIN OUTCOME
      MEASURE(S): Scapular posterior tilt, upward rotation, and external rotation were
      examined across elbow-extension ROM and compared across conditions. RESULTS:
      Posterior tilt was greater in the self-selected and at-side conditions than in
      the elevated condition and increased linearly with elbow extension. External
      rotation was greater in the self-selected and at-side conditions compared with
      that in the elevated condition. In the at-side condition, upward rotation began
      lower than in the other conditions at the start of the concentric phase but
      increased above the others soon after the elbow started to extend. CONCLUSIONS:
      Performing a traditional push-up with the shoulders elevated may place the
      scapula in a position of impingement. Clinicians should be cognizant of shoulder
      elevation when prescribing and monitoring exercise progression. The results of
      this study will provide further direction for clinicians in prescribing
      rehabilitation exercises for the upper extremity, especially closed chain
      exercises for shoulder conditions.

PMID- 23952044
TI  - Sport and team differences on baseline measures of sport-related concussion.
AB  - CONTEXT: With the advent of the National Collegiate Athletic Association's
      (NCAA's) mandating the presence and practice of concussion-management plans in
      collegiate athletic programs, institutions will consider potential approaches for
      concussion management, including both baseline and normative comparison
      approaches. OBJECTIVE: To examine sport and team differences in baseline
      performance on a computer-based neurocognitive measure and 2 standard sideline
      measures of cognition and balance and to determine the potential effect of
      premorbid factors sex and height on baseline performance. DESIGN: Cross-sectional
      study. SETTING: University laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of
      437 NCAA Division II student-athletes (males = 273, females = 164; age = 19.61 +/
      1.64 years, height = 69.89 +/- 4.04 inches [177.52 +/- 10.26 cm]) were recruited
      during mandatory preseason testing conducted in a concussion-management program.
      MAIN OUTCOME MEASURE(S): The computerized Concussion Resolution Index (CRI), the
      Standardized Assessment of Concussion (Form A; SAC), and the Balance Error
      Scoring System (BESS). RESULTS: Players on the men's basketball team tended to
      perform worse on the baseline measures, whereas soccer players tended to perform
      better. We found a difference in total BESS scores between these sports (P =
      .002). We saw a difference between sports on the hard-surface portion of the BESS
      (F6,347 = 3.33, P = .003, etap(2) = 0.05). No sport, team, or sex differences
      were found with SAC scores (P > .05). We noted differences between sports and
      teams in the CRI indices, with basketball, particularly the men's team,
      performing worse than soccer (P < .001) and softball/baseball (P = .03). When sex
      and height were considered as possible sources of variation in BESS and CRI team
      or sport differences, height was a covariate for the team (F1,385 = 5.109, P =
      .02, etap(2) = 0.013) and sport (F1,326 = 11.212, P = .001, etap(2) = 0.033)
      analyses, but the interaction of sex and sport on CRI indices was not significant
      in any test (P > .05). CONCLUSIONS: Given that differences in neurocognitive
      functioning and performance among sports and teams exist, the comparison of
      posttraumatic and baseline assessment may lead to more accurate diagnoses of
      concussion and safer return-to-participation decision making than the use of
      normative comparisons.

PMID- 23952045
TI  - Motion in the unstable cervical spine when transferring a patient positioned
      prone to a spine board.
AB  - CONTEXT: Two methods have been proposed to transfer an individual in the prone
      position to a spine board. Researchers do not know which method provides the best
      immobilization. OBJECTIVE: To determine if motion produced in the unstable
      cervical spine differs between 2 prone logrolling techniques and to evaluate the
      effect of equipment on the motion produced during prone logrolling. DESIGN:
      Crossover study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Tests were
      performed on 5 fresh cadavers (3 men, 2 women; age = 83 +/- 8 years, mass = 61.2
      +/- 14.1 kg). MAIN OUTCOME MEASURE(S): Three-dimensional motions were recorded
      during 2 prone logroll protocols (pull, push) in cadavers with an unstable
      cervical spine. Three equipment conditions were evaluated: football shoulder pads
      and helmet, rigid cervical collar, and no equipment. The mean range of motion was
      calculated for each test condition. RESULTS: The pull technique produced 16% more
      motion than the push technique in the lateral-bending angulation direction (F1,4
      = 19.922, P = .01, eta(2) = 0.833). Whereas the collar-only condition and, to a
      lesser extent, the football-shoulder-pads-and-helmet condition demonstrated
      trends toward providing more stability than the no-equipment condition, we found
      no differences among equipment conditions. We noted an interaction between
      technique and equipment, with the pull maneuver performed without equipment
      producing more anteroposterior motion than the push maneuver in any of the
      equipment conditions. CONCLUSIONS: We saw a slight difference in the motion
      measured during the 2 prone logrolling techniques tested, with less lateral
      bending and anteroposterior motion produced with the logroll push than the pull
      technique. Therefore, we recommend adopting the push technique as the preferred
      spine-boarding maneuver when a patient is found in the prone position.
      Researchers should continue to seek improved methods for performing prone spine
      board transfers to further decrease the motion produced in the unstable spine.

PMID- 23952046
TI  - Inhibition of interleukin 1beta-stimulated interleukin-6 production by cranberry
      components in human gingival epithelial cells: effects on nuclear factor kappaB
      and activator protein 1 activation pathways.
AB  - BACKGROUND AND OBJECTIVE: In periodontitis, gingival epithelial cells can produce
      interleukin (IL)-6, a regulator of osteoclastic bone resorption, in response to
      IL-1beta. IL-1beta regulates cytokine expression via signaling pathways,
      including nuclear factor (NF)-kappaB and mitogen activated protein kinase
      (MAPK)/activator protein (AP)-1. Cranberry proanthocyanidins (PACs) inhibit IL
      1beta-stimulated IL-6 production, but specific mechanisms are unclear. The
      objectives of this study were to determine effects of cranberry PACs on NF-kappaB
      and MAPK/AP-1 activation of IL-1beta-stimulated IL-6 production in gingival
      epithelial cells. MATERIAL AND METHODS: Cranberry high molecular weight non
      dialyzable material (NDM), rich in PACs, was derived from cranberry juice. Human
      gingival epithelial cells [Smulow-Glickman (S-G)] were incubated with IL-1beta in
      the presence or absence of NDM or inhibitors of NF-kappaB, [nemo-binding domain
      (NBD) peptide] or AP-1 (SP600125), and IL-6 levels were measured by ELISA.
      Effects of NDM on IL-1beta-activated NF-kappaB and AP-1 and phosphorylated
      intermediates in both pathways were measured in cell extracts via binding to
      specific oligonucleotides and specific sandwich ELISAs, respectively. Data were
      analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons. RESULTS:
      IL-1beta (>= 0.1 nm) caused a time- and dose-dependent stimulation of S-G
      epithelial cell IL-6 production (p < 0.005). This was significantly decreased in
      a dose-dependent manner by NBD peptide or SP600125 [maximum inhibition ~30-40% (p
      < 0.02)], and together, the two inhibitors decreased IL-6 by ~80%, similar to the
      inhibition caused by NDM (p < 0.001). IL-1beta stimulated NF-kappaB and AP-1
      activation (p < 0.003), which was inhibited by NDM (p < 0.0001). NDM did not
      significantly affect IL-1beta-stimulated levels of phosphorylated intermediates
      in the NF-kappaB pathway (IkappaBalpha) or the AP-1 pathway (c-Jun, ERK1/2).
      CONCLUSION: In S-G epithelial cells, IL-1beta appeared to upregulate IL-6
      production via activation of both NF-kappaB and MAPK/AP-1 signaling pathways
      because cranberry NDM decreased nuclear levels of IL-1beta-activated NF-kappaB
      (p65) and AP-1 (phospho-c-Jun) and strongly inhibited IL-6 production. Lack of
      inhibition of phosphorylation of IkappaBalpha, c-Jun or ERK1/2 suggested that NDM
      might affect both pathways downstream from those points in S-G cells, such as
      ubiquitination and proteosomal degradation of IkappaBalpha, or inhibition of
      nuclear activity of c-Jun and/or ERK1/2. Defining these points of inhibition
      precisely may help identify molecular targets of cranberry polyphenols.

PMID- 23952047
TI  - RIP2/RICK-dependent cytokine production upon Yersinia enterocolitica infection in
      macrophages with TLR4 deficiency.
AB  - Receptor-interacting protein 2 (RIP2) is a caspase recruitment domain (CARD)
      containing serine/threonine kinase that is activated by NOD1 or NOD2 recognition
      of their ligands and essential for the activation of NF-kappaB and mitogen
      activated protein kinase (MAPK). RIP2 has been known to play an important role in
      innate immune responses against certain bacterial infection. However, the role
      and interplay of RIP2 with TLR signalling on cytokine production in macrophages
      against Yersinia enterocolitica infection remains poorly understood. In the
      present study, we examined whether RIP2 is essential for Yersinia-induced
      production of cytokines in macrophages. Our results showed that naive RIP2
      deficient macrophages produced similar level of IL-6, TNF-alpha and IL-10 upon Y.
      enterocolitica infection compared with wild-type macrophages. However, the
      production of IL-6, TNF-alpha and IL-10 by Y. enterocolitica was impaired in RIP2
      deficient macrophages after lipopolysaccharide (LPS) pretreatment, a TLR4
      tolerant condition. In addition, RIP2 inhibitors, SB203580, PP2, and gefitinib,
      reduced IL-6 production in TLR4-deficient macrophages in response to Y.
      enterocolitica, whereas they did not affect the cytokines production in WT cells.
      These results demonstrate that RIP2 may play an important role in proinflammatory
      cytokine production in macrophages at the absence of TLR signalling.

PMID- 23952048
TI  - Successful pregnancy complicated by spontaneous, familial, recurrent ovarian
      hyperstimulation syndrome: report of two cases.
AB  - We here report two cases of spontaneous, familial, recurrent ovarian
      hyperstimulation syndrome ended in a successful pregnancy. First case was a 26
      year-old woman, gravida 3 para 0 and two previous terminations of pregnancy due
      to spontaneous ovarian hyperstimulation syndrome (OHSS). During her pregnancy,
      patient was treated with IV fluid therapy, albumin and thromboembolic prophylaxis
      and required pleural and peritoneal drainage. She was referred to the hospital
      twice, at 8 and 28 weeks'. At 32 weeks due to worsening of clinical condition,
      decision was made for a caesarean section. A live, healthy preterm baby of 1950 g
      was delivered. Second case was a 27-year-old woman, gravida 2 para 0 with one
      previous termination of pregnancy due to spontaneous OHSS. During her pregnancy
      patient was treated with IV fluid therapy, albumin, and thromboembolic
      prophylaxis. She did not require any pleural or peritoneal drainage. She was
      referred to the hospital twice, at 8 and 30 weeks. At 37 weeks of gestation, due
      to worsening of clinical condition decision for a caesarean section was made. A
      live, healthy term baby of 2700 g was delivered. Our experience seems to confirm
      that management of spontaneous OHSS during pregnancy should be conservative and
      treatment tailored to severity of symptoms.

PMID- 23952049
TI  - Association study of the TNF-alpha -1031T/C and VEGF +450G/C polymorphisms with
      susceptibility to endometriosis.
AB  - Tumor necrosis factor-alpha (TNF-alpha), a multifunctional proinflammatory
      cytokine, and vascular endothelial growth factor (VEGF), a major mediator of
      angiogenesis and vascular permeability, have been investigated in endometriosis
      patients of different populations. This study was carried out to investigate
      whether the two polymorphisms, TNF-alpha -1031T/C and VEGF +450G/C are associated
      with susceptibility to endometriosis in an Iranian population. Totally, 135 women
      with diagnosis of endometriosis and 173 women with no evidence of the disease
      were included in this study. The -1031T/C and +450G/C polymorphisms were assessed
      by PCR-RFLP analysis, using the two restriction enzymes BbsI and BsmFI,
      respectively. The frequencies of the TNF-alpha -1031TC genotype (p = 0.038) and
      the -1031 C allele (p = 0.048) were significantly lower in patients than control
      group. In contrast, no significant differences in the genotype and allele
      frequencies of the VEGF +450G/C polymorphism were found between the case and
      control groups. Our results suggest that the TNF-alpha -1031T/C polymorphism was
      associated with susceptibility to endometriosis in Iranian population, and the 
      1301C allele may have a protective role in development of endometriosis; On the
      contrary, we find no association between the VEGF +450G/C polymorphism and risk
      of endometriosis.

PMID- 23952050
TI  - Novel Collimated Beam Setup to Study the Kinetics of VUV-Induced Reactions.
AB  - Vacuum UV (VUV) process is an incipient advanced oxidation process, which can be
      used for water treatment. This process relies on the formation of hydroxyl
      radicals through the VUV-induced photolysis of water. In particular, the use of
      ozone-generating mercury vapor lamps, which emit 10% of the radiation at 185 nm
      and 90% at 254 nm, is showing very promising results for the degradation of
      micropollutants. The kinetics of VUV process has been studied in batch- and flow
      through reactors, but the effect of 254 and 185 nm photons cannot be isolated,
      mass transfer resistances can take place and the interpretation of the results is
      complex. In this technical note, a new VUV collimated beam to conduct kinetic
      tests is presented, which offers several advantages: (1) it allows the
      irradiation of samples with 185, 254 nm photons, or both, (2) the concentration
      of reagents is uniform in the reaction volume and (3) it allows to change the
      fluence rate by changing the distance between the lamp and the photoreactor.
      Details of the geometry are presented, as well as an analysis of the collimation
      and uniformity of the radiation of the new VUV-collimated beam setup.

PMID- 23952051
TI  - Clopidogrel reduces post-transplant obliterative bronchiolitis.
AB  - Survival after lung transplantation is mainly limited by the development of
      chronic lung allograft dysfunction (CLAD). The aim of this study was to
      investigate if platelet inhibition by clopidogrel has an influence on the
      formation of obliterative bronchiolitis, the histopathological correlate to
      bronchiolitis obliterans syndrome, present in the majority of patients suffering
      from CLAD. C57Bl/6(H2(b) ) donor tracheas were orthotopically transplanted into
      CBA.J(H2(k) ). Mice received different doses of clopidogrel alone or in
      combination with tacrolimus or everolimus. Grafts were analyzed by histology and
      immunofluorescence method on postoperative days 15, 30 or 60. Cytokines were
      analyzed by real-time polymerase chain reaction on postoperative day 21 and
      alloantibodies by FACS. Mice treated with 20 mg/kg/day clopidogrel for 30 days
      showed reduced obliteration [34.40 +/- 3.76% (20 mg/kg/day clopidogrel) vs. 49.92
      +/- 2.11% (control), n = 5, P < 0.05]. Platelet inhibition resulted in
      significant lower infiltration of T cells and macrophages, and we also found
      significantly lower expression of IL-12, IL-4, IL-6, TNF-alpha, TGF-beta,
      PDGFbeta, MCP1, P-/E-selectin, ICAM1 and CD40L after treatment with clopidogrel.
      Combination of 1 mg/kg/day clopidogrel and 0.05 mg/kg/day everolimus or 12
      mg/kg/day tacrolimus revealed a synergistic effect. Humoral immunity as
      manifested by donor-specific alloantibody secretion was also impaired after
      treatment with clopidogrel. Here, we can show that platelet inhibition by
      clopidogrel as a single treatment and in combination with tacrolimus or
      everolimus reduced the development of fibrosis and obliteration in tracheal
      allografts. 

PMID- 23952052
TI  - Q10-triggered facial vitiligo.
AB  - BACKGROUND: Generation and accumulation of reactive oxygen/nitrogen species in
      the epidermis of patients with vitiligo has been widely documented. Moreover,
      semiquinone radical-mediated sensitivity has been shown in blood lymphocytes of
      these patients. OBJECTIVES: To determine the possible mechanism behind Q10
      induced facial vitiligo. METHODS: This was a clinical assessment supported by in
      vivo Fourier transform-Raman spectroscopy and repigmentation. RESULTS: Topical
      Q10 application generated hydrogen peroxide (H2 O2 ) leading in turn to facial
      vitiligo in susceptible individuals. Proof of the basic result stemmed from
      reduction of epidermal H2 O2 by using narrowband ultraviolet B-activated
      propseudocatalase PC-KUS in association with cessation of depigmentation and
      repigmentation of the lost skin colour. CONCLUSIONS: Over-the-counter
      availability of Q10-containing topical formulations can be harmful to individuals
      susceptible to vitiligo.

PMID- 23952053
TI  - Nitric oxide releasing photoresponsive nanohybrids as excellent therapeutic agent
      for cervical cancer cell lines.
AB  - Gold nanoparticles (GNPs) that can release nitric oxide (NO) on visible-light
      irradiation were prepared using 2-mercapto-5-nitro benzimidazole (MNBI) as
      stabilizer. These nanoparticles meet overall prerequisites for biomedical
      applications like small sizes, water solubility, and stability. It was found that
      even a very low dosage of MNBI-stabilized GNPs exhibit appreciable tumor cell
      mortality against cervical cancer cell lines, demonstrating the role of NO in
      killing cancer cells. 

PMID- 23952054
TI  - Lipid bilayers significantly modulate cross-fibrillation of two distinct
      amyloidogenic peptides.
AB  - Amyloid plaques comprising misfolded proteins are the hallmark of several
      incurable diseases, including Alzheimer's disease, type-II diabetes, Jacob
      Creutzfeld disease, and others. While the exact molecular mechanisms underlying
      protein misfolding diseases are still unknown, several theories account for
      amyloid fiber formation and their toxic significance. Prominent among those is
      the "prion hypothesis" stipulating that misfolded protein seeds act as
      "infectious agents" propagating aggregation of nominally healthy, native
      proteins. Recent studies, in fact, have reported that interactions between
      different amyloid peptides that are partly sequence-related might also affect
      fibrillation pathways and pathogenicity. Here, we present evidence that two
      structurally and physiologically unrelated amyloidogenic peptides, the islet
      amyloid polypeptide (IAPP, the peptide comprising the amyloid aggregates in type
      II diabetes) and an amyloidogenic determinant of the prion protein (PrP), give
      rise to a significantly distinct fibrillation pathway when they are incubated
      together in the presence of membrane bilayers. In particular, the experimental
      data demonstrate that the lipid bilayer environment is instrumental in initiating
      and promoting the assembly of morphologically distinct fibrillar species.
      Moreover, cross-fibrillation produced peptide species exhibiting significantly
      altered membrane interaction profiles, as compared to the scenario where the two
      peptides aggregated separately. Overall, our data demonstrate that membranes
      constitute a critical surface-active medium for promoting interactions between
      disparate amyloidogenic peptides, modulating both fibrillation pathways as well
      as the biophysical properties of the peptide aggregates. This work hints that
      membrane-induced cross-fibrillation of unrelated amyloidogenic peptides might
      play an insidious role in the molecular pathologies of protein misfolding
      diseases. 

PMID- 23952056
TI  - Peneciraistin C induces caspase-independent autophagic cell death through
      mitochondrial-derived reactive oxygen species production in lung cancer cells.
AB  - Peneciraistin C (Pe-C) is a novel spiroketal compound isolated from the saline
      soil derived fungus Penicillium raistrickii. Our previous study showed that Pe-C
      exerted a potent cytotoxic effect on many kinds of cancer cell lines, especially
      on human lung cancer A549 cells. Here, we report the anticancer mechanisms of Pe
      C in a variety of lung cancer cells. The results showed that Pe-C induced caspase
      independent autophagic cell death and elevated mitochondrial-derived reactive
      oxygen species levels. Interestingly, if autophagy was blocked by 3-methyladenine
      or Atg5 siRNA, Pe-C triggered a shift from autophagic cell death into caspase
      dependent apoptotic cell death. In addition, cotreatment with the antioxidant N
      acetyl-(L)-cysteine or Mito-TEMPO could effectively reverse the effect of the
      enhanced reactive oxygen species production, which in turn almost completely
      prevented the cell death induced by Pe-C. Thus, this study provided new insights
      into the mechanisms underlying Pe-C-mediated cell death, which indicated that Pe
      C could be a potential drug candidate for therapy of lung cancers.

PMID- 23952055
TI  - Environmental determinants of polychlorinated biphenyl concentrations in
      residential carpet dust.
AB  - Polychlorinated biphenyls (PCBs), banned in the United Sates in the late 1970s,
      are still found in indoor and outdoor environments. Little is known about the
      determinants of PCB levels in homes. We measured concentrations of five PCB
      congeners (105, 138, 153, 170, and 180) in carpet dust collected between 1998 and
      2000 from 1187 homes in four sites: Detroit, Iowa, Los Angeles, and Seattle. Home
      characteristics, occupational history, and demographic information were obtained
      by interview. We used a geographic information system to geocode addresses and
      determine distances to the nearest major road, freight route, and railroad;
      percentage of developed land; number of industrial facilities within 2 km of
      residences; and population density. Ordinal logistic regression was used to
      estimate the associations between the covariates of interest and the odds of PCB
      detection in each site separately. Total PCB levels [all congeners < maximum
      practical quantitation limit (MPQL) vs at least one congener >= MPQL to < median
      concentration vs at least one congener > median concentration] were positively
      associated with either percentage of developed land [odds ratio (OR) range 1.01
      1.04 for each percentage increase] or population density (OR 1.08 for every
      1000/mi(2)) in each site. The number of industrial facilities within 2 km of a
      home was associated with PCB concentrations; however, facility type and direction
      of the association varied by site. Our findings suggest that outdoor sources of
      PCBs may be significant determinants of indoor concentrations. 

PMID- 23952057
TI  - Long-term clinical outcomes of fat grafting by low-pressure aspiration and slow
      centrifugation (Lopasce technique) for different indications.
AB  - Autologous fat grafts have been used successfully for structural fat grafting in
      facial, lip, and hand rejuvenation, body contour improvement, and traumatic
      defect restoration. The purposes of this study were to define a new fat graft
      harvesting and processing technique, which is named the "Lopasce technique" (low
      pressure aspiration and slow centrifugation technique), and to evaluate the late
      clinical outcomes of fat grafting by this technique for different indications. A
      retrospective study was performed using the medical records of 21 patients (17
      women and four men). The mean injected fat volume was 33.2 +/- 34 cc (range 6-125
      cc). The mean follow-up period was 13.2 +/- 5.6 months (range 6-26 months).
      Postoperative results were evaluated by subjective and objective methods. In the
      subjective evaluation, 19 patients stated that there had been little resorption
      and that it was not necessary to repeat the fat grafting, one patient reported
      that the fat was resorbed in part, and one patient reported that the fat was
      resorbed completely. In the objective evaluation, the amount of fat graft taken
      in the recipient sites was between 60%-80% (average 70%) when compared with
      preoperative and late postoperative photographs of the patients at the 6- and 26
      month follow-ups. Fat grafting is a simple, effective, and reproducible technique
      with a high satisfaction rate and few disadvantages or complications. We consider
      that structural fat grafting with the lopasce technique is an easy, effective,
      and long-lasting treatment for correction of congenital or acquired defects
      associated with various medical conditions.

PMID- 23952058
TI  - Converting NAD-specific inositol dehydrogenase to an efficient NADP-selective
      catalyst, with a surprising twist.
AB  - myo-Inositol dehydrogenase (IDH, EC 1.1.1.18) from Bacillus subtilis converts myo
      inositol to scyllo-inosose and is strictly dependent on NAD for activity. We
      sought to alter the coenzyme specificity to generate an NADP-dependent enzyme in
      order to enhance our understanding of coenzyme selectivity and to create an
      enzyme capable of recycling NADP in biocatalytic processes. Examination of
      available structural information related to the GFO/MocA/IDH family of
      dehydrogenases and precedents for altering coenzyme selectivity allowed us to
      select residues for substitution, and nine single, double, and triple mutants
      were constructed. Mutagenesis experiments with B. subtilis IDH proved extremely
      successful; the double mutant D35S/V36R preferred NADP to NAD by a factor of 5.
      This mutant is an excellent catalyst with a second-order rate constant with
      respect to NADP of 370 000 s-1 M-1, and the triple mutant A12K/D35S/V36R had a
      value of 570 000 s-1 M-1, higher than that of the wild-type IDH with NAD. The
      high-resolution X-ray crystal structure of the double mutant A12K/D35S was solved
      in complex with NADP. Surprisingly, the binding of the coenzyme is altered such
      that although the nicotinamide ring maintains the required position for
      catalysis, the coenzyme has twisted by nearly 90 degrees , so the adenine moiety
      no longer binds to a hydrophobic cleft in the Rossmann fold as in the wild-type
      enzyme. This change in binding conformation has not previously been observed in
      mutated dehydrogenases.

PMID- 23952059
TI  - The impact of problem-based learning on clinical reasoning in occupational
      therapy education.
AB  - This study addressed the influence of Problem-Based Learning (PBL) on clinical
      reasoning skills in occupational therapy students. PBL is an educational method
      proposed to facilitate clinical reasoning and a repertoire of problem-solving
      skills. Occupational Performance Approaches is a course offered to students
      during the summer of the fifth year of coursework. It incorporates PBL in the
      laboratory portion. This study focused on 22 non-traditional students
      participating in the lecture and laboratory portion of this course to determine
      the influence, if any, that PBL had on clinical reasoning. The results of this
      study demonstrated that PBL did not impact students' clinical reasoning during
      the eight-week time frame. 

PMID- 23952060
TI  - Model of competence: a conceptual framework for understanding the person
      environment interaction for persons with motor disabilities.
AB  - The "Model of Competence" has been recently elaborated to help expand our
      understanding relating to a person's interaction with the environment.
      Specifically, it seeks to deal with the issues related to the home adaptation
      (the home layout and equipment) for a person living with motor disabilities. This
      theoretical model takes into account various characteristics of the person as
      well as of the environment, by re-grouping six concepts: person, environment,
      activity, role, competence and handicap situation. The "Model of Competence" is
      distinct because it includes: (1) both the human and the nonhuman dimension of
      the environment; (2) personal characteristics other than the strictly physical
      ones; (3) a clear identification of the interaction between the person and the
      environment; and (4) a means of operationalizing it via an assessment instrument.
      This model proposes an innovative approach to the person-environment relation in
      terms of personalizing accessibility, and thereby offers a new approach to
      understanding the concept of universal access. It has been developed for research
      and application, and addresses several disciplines. 

PMID- 23952061
TI  - Field work: A Road to Employment.
AB  - While the goal of occupational therapy fieldwork education is to prepare entry
      level practitioners, over time, it has been linked to various professional
      concerns including: the graduate's selection of practice area; recruitment
      practices; and the job market. In light of these issues and the current changes
      in the health care arena, the authors explored the relationship between fieldwork
      and employment of an OT program's graduates. 

PMID- 23952062
TI  - The use of theory in everyday practice: an exploratory study.
AB  - PURPOSE: This exploratory study, using a phenomenological framework with
      ethnographic methodology investigated the use of theory in everyday practice as
      described by three registered occupational therapists. METHOD: Semi-structured
      interviews were conducted with three practicing occupational therapists.
      Ethnographic observations and field notes supplemented the data collection. Data
      were analyzed using qualitative techniques. RESULTS: Six major themes emerged
      from the interview data and were supported by the observational data: (1)"This is
      where I kind of get confused."(2)"I remember hearing about theory."(3)"It helps
      me."(4)"I don't think there's a particular reason."(5)"We rarely use the
      terminology." (6)"It's kind of hard to incorporate that." DISCUSSION: The lack of
      the use of theory is paradoxical since all three therapists valued its use and
      saw it as a way to distinguish occupational therapy from other professions. The
      lack of use may be due to inadequate educational preparation, pragmatic issues
      prevalent in clinical sites, and lack of role models. An alternative learning
      strategy is provided.

PMID- 23952063
TI  - Annotated bibliography of chaos for occupational therapy.
AB  - Given the level of complexity at which the practice of occupational therapy
      operates, chaos may be the key to fresh insight into the nature of occupation.
      This article, through an innovative scholarly format-the annotation-presents
      essential concepts of chaos theory which are relevant for occupational therapy. A
      rationale for the importance of chaos theory and complexity science is presented
      and the limited extent to which chaos theory has been addressed in the
      occupational therapy literature is identified. Occupational therapy links to
      chaos and complexity are delineated and explained based upon a review of fourteen
      articles appearing in peer reviewed journals over a five year period (1993-1998),
      which are presented in three categories: (a) interdisciplinary applications, (b)
      mental health and creativity applications, and (c) educational and research
      applications. Conclusions about the relevance of chaos theory to occupational
      therapy are presented in the last section of the paper. 

PMID- 23952064
TI  - Classification of fieldwork experiences for the new millennium.
AB  - Occupational therapists are seeking opportunities in new practice arenas due to
      health care changes, identification of occupation-based needs in the community
      and a renewed dedication to occupation-centered care. It is imperative that the
      profession continue to meet the demands of a changing work environment by
      adequately preparing occupational therapy students. Innovative activities in a
      variety of settings are increasingly used by educational programs to provide
      fieldwork experiences for students. Descriptions and definitions of these new
      types of experiences will provide a format for consistent terminology and further
      enhance optimal involvement in newer arenas. 

PMID- 23952066
TI  - Breaking aggregation and driving the keto-to-gem-diol equilibrium of the N,N'
      dimethyl-2,6-diaza-9,10-anthraquinonediium dication to the keto form by
      intercalation in cucurbit[7]uril.
AB  - (1)H NMR, ESI-MS, and DFT calculations with the M062X/6-31G* method show that, in
      water, the bistetrafluoroborate salt of N,N'-dimethyl-2,6-diaza-9,10
      anthraquinonediium dication (DAAQ.2BF4(-)) exists in equilibrium with both its
      gem-diol and several aggregates (from dimers to at least octamers). With high
      concentrations of HCl (e.g., 1.2-1.5 M), all aggregates break up and the keto-to
      gem-diol equilibrium is shifted quantitatively toward the quinone form. The same
      effect is observed with 1.5 mol equiv of cucurbit[7]uril, CB[7], with which all
      equilibria are shifted toward the quinone form, which undergoes slow exchange
      with the CB[7] cavity as both the free and the CB[7]-intercalated quinone
      (DAAQ@CB[7]) are observed simultaneously by (1)H NMR. The affinity of DAAQ for
      the CB[7] cavity (Keq = 4 * 10(6) M(-1)) is in the range found for tricyclic dyes
      (0.4-5.4 * 10(6) M(-1)), and among the highest observed to date. A computational
      comparative study of the corresponding CB[7] complex of the N,N'-dimethyl-4,4'
      bipyridinium dication (N,N'-dimethyl viologen, MeV) suggests that the higher
      binding constant for intercalation of DAAQ may be partially attributed to a
      lesser distortion of CB[7] (required to maximize favorable nonbonding
      interactions) as a result of the flat geometry of DAAQ. 

PMID- 23952067
TI  - The impact of microbial symbionts on host plant utilization by herbivorous
      insects.
AB  - Herbivory, defined as feeding on live plant tissues, is characteristic of highly
      successful and diverse groups of insects and represents an evolutionarily derived
      mode of feeding. Plants present various nutritional and defensive barriers
      against herbivory; nevertheless, insects have evolved a diverse array of
      mechanisms that enable them to feed and develop on live plant tissues. For
      decades, it has been suggested that insect-associated microbes may facilitate
      host plant use, and new molecular methodologies offer the possibility to
      elucidate such roles. Based on genomic data, specialized feeding on phloem and
      xylem sap is highly dependent on nutrient provisioning by intracellular
      symbionts, as exemplified by Buchnera in aphids, although it is unclear whether
      such symbionts play a substantive role in host plant specificity of their hosts.
      Microorganisms present in the gut or outside the insect body could provide more
      functions including digestion of plant polymers and detoxification of plant
      produced toxins. However, the extent of such contributions to insect herbivory
      remains unclear. We propose that the potential functions of microbial symbionts
      in facilitating or restricting the use of host plants are constrained by their
      location (intracellular, gut or environmental), and by the fidelity of their
      associations with insect host lineages. Studies in the next decade, using
      molecular methods from environmental microbiology and genomics, will provide a
      more comprehensive picture of the role of microbial symbionts in insect
      herbivory. 

PMID- 23952068
TI  - Spatially resolved mapping of electrical conductivity across individual domain
      (grain) boundaries in graphene.
AB  - All large-scale graphene films contain extended topological defects dividing
      graphene into domains or grains. Here, we spatially map electronic transport near
      specific domain and grain boundaries in both epitaxial graphene grown on SiC and
      CVD graphene on Cu subsequently transferred to a SiO2 substrate, with one-to-one
      correspondence to boundary structures. Boundaries coinciding with the substrate
      step on SiC exhibit a significant potential barrier for electron transport of
      epitaxial graphene due to the reduced charge transfer from the substrate near the
      step edge. Moreover, monolayer-bilayer boundaries exhibit a high resistance that
      can change depending on the height of substrate step coinciding at the boundary.
      In CVD graphene, the resistance of a grain boundary changes with the width of the
      disordered transition region between adjacent grains. A quantitative modeling of
      boundary resistance reveals the increased electron Fermi wave vector within the
      boundary region, possibly due to boundary induced charge density variation.
      Understanding how resistance change with domain (grain) boundary structure in
      graphene is a crucial first step for controlled engineering of defects in large
      scale graphene films. 

PMID- 23952070
TI  - Epidermal response of rainbow trout to Ichthyobodo necator: immunohistochemical
      and gene expression studies indicate a Th1-/Th2-like switch.
AB  - Infections with the parasitic flagellate Ichthyobodo necator (Henneguy, 1883)
      cause severe skin and gill disease in rainbow trout Oncorhynchus mykiss (Walbaum,
      1792) juveniles. The epidermal disturbances including hyperplasia and mucous cell
      exhaustion caused by parasitization are known, but no details on specific
      cellular and humoral reactions have been presented. By applying gene expression
      methods and immunohistochemical techniques, further details of immune processes
      in the affected skin can be presented. A population of I. necator was established
      in the laboratory and used to induce an experimental infection of juvenile
      rainbow trout. The course of infection was followed by sampling for parasite
      enumeration, immunohistochemistry (IHC) and quantitative PCR (qPCR) on days 0, 5,
      9 and 14 post-infection. IHC showed a significant increase in the occurrence of
      IgM-positive cells in the skin of the infected fish, whereas IgT-positive cells
      were eliminated and the number of CD8-positive cells declined. qPCR studies
      supported the IHC findings showing a significant increase in IgM and a decrease
      in the CD8 gene expression. In addition, genes encoding innate immune genes such
      as lysozyme, SAA and cathelicidin 2 were up-regulated. Expression of cytokines
      (IL-1beta, IL-4/13A, IL-6, IL-8, IL-10), the cell marker CD4 and the
      transcription factor GATA3 showed a significant increase after infection.
      Cytokine profiling including up-regulation of IL-4/13A and IL-10 genes and
      transcription factor GATA3 connected to the proliferation of IgM producing
      lymphocytes suggests a partial shift towards a Th2 response associated with the
      I. necator infection. 

PMID- 23952071
TI  - Temperature-induced coexistence of a conducting bilayer and the bulk-terminated
      surface of the topological insulator Bi2Te3.
AB  - Topological insulators such as Bi2Se3 and Bi2Te3 have extremely promising
      transport properties, due to their unique electronic behavior: they are
      insulators in the bulk and conducting at the surface. Recently, the coexistence
      of two types of surface conducting channels has been observed for Bi2Se3, one
      being Dirac electrons from the topological state and the other electrons from a
      conventional two-dimensional gas. As an explanation for this effect, a possible
      structural modification of the surface of these materials has been hypothesized.
      Using scanning tunneling microscopy we have directly observed the coexistence of
      a conducting bilayer and the bare surface of bulk-terminated Bi2Te3. X-ray
      crystal truncation rod scattering was used to directly show the stabilization of
      this epitaxial bilayer which is primarily composed of bismuth. Using this
      information, we have performed density functional theory calculations to
      determine the electronic properties of the possible surface terminations. They
      can be used to understand recent angular resolved photoemission data which have
      revealed this dual surface electronic behavior. 

PMID- 23952074
TI  - The association between detectable plasmatic human immunodeficiency virus (HIV)
      viral load and different subgingival microorganisms in Brazilian adults with HIV:
      a multilevel analysis.
AB  - BACKGROUND: This study investigates the association between detectable plasmatic
      human immunodeficiency virus (HIV) viral load (HVL) and high levels of
      periodontal- and non-periodontal-related microorganisms in the subgingival
      microbiota of individuals with HIV. METHODS: Thirty-seven individuals with HIV
      were divided into two groups: 1) detectable HVL (n = 15); and 2) undetectable HVL
      (n = 22). Subgingival biofilm samples were obtained, and the levels of 35
      microbial species were determined by the checkerboard DNA-DNA hybridization
      method. Periodontal clinical measures and laboratory and sociodemographic data
      were also registered. chi(2) test, Fisher exact test, and Mann-Whitney U test
      were used to compare groups. Multilevel ordinal regression models were used to
      test the association between HVL and the levels of 35 microbial species in
      subgingival biofilm, adjusted for confounders. RESULTS: Of the 35 species
      studied, 11 (31.4%) showed higher mean levels in the detectable HVL group than
      undetectable HVL group (P <0.001). These species included Actinomyces naeslundii
      II, Actinomyces israelii, Actinomyces odontolyticus, Veillonella parvula,
      Capnocytophaga gingivalis, Eikenella corrodens, Campylobacter concisus,
      Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Candida
      albicans. Significant associations between detectable HVL and high levels of
      microorganisms, adjusted for confounders, were observed for A. naeslundii I,
      Actinomyces gerencseriae, C. gingivalis, E. corrodens, C. concisus, Prevotella
      nigrescens, T. forsythia, and Dialister pneumosintes. CONCLUSION: Detectable
      plasmatic HVL in individuals with HIV was associated with elevated levels of
      known periodontal pathogens, such as P. nigrescens, T. forsythia, and E.
      corrodens, as well as C. concisus, C. gingivalis, and D. pneumosintes in the
      subgingival biofilm.

PMID- 23952075
TI  - Saliva and serum levels of pentraxin-3 and interleukin-1beta in generalized
      aggressive or chronic periodontitis.
AB  - BACKGROUND: Pentraxin-3 (PTX3) is a multifactorial protein involved in immunity
      and inflammation, which is rapidly produced and released by several cell types in
      response to inflammatory signals. The aim of the present study is to evaluate
      saliva, serum levels of PTX3, interleukin (IL)-1beta in patients with generalized
      chronic periodontitis (CP) or aggressive periodontitis (AgP), and periodontally
      healthy individuals. METHODS: A total of 94 participants (25 patients with AgP,
      25 patients with CP, and 44 periodontally healthy individuals matched with AgP
      and CP groups) were recruited. Saliva and serum samples were collected. Clinical
      periodontal measurements were recorded. PTX3, IL-1beta levels in serum, and
      saliva samples were determined by enzyme-linked immunosorbent assay. Data were
      tested statistically using Kruskal-Wallis, Mann-Whitney U, and Spearman rho rank
      test. RESULTS: Serum and saliva data were similar in CP and AgP groups. Saliva
      levels of IL-1beta were significantly higher in the AgP and CP groups than
      controls (P <0.05). Salivary PTX3 levels were similar in the CP and control
      groups. Significantly higher salivary concentrations of PTX3 were detected in the
      AgP group than the control group (P <0.05). Saliva PTX3 levels correlated with
      plaque index and bleeding on probing in the CP group (P <0.05). Serum and saliva
      PTX3 levels correlated with those of IL-1beta in the AgP group (P <0.05).
      CONCLUSIONS: It may be suggested that PTX3 is related with periodontal tissue
      inflammation. Its salivary concentrations may have a diagnostic potential.
      Additional intervention and follow-up studies coupling PTX3 concentrations with
      microbiologic analysis would better clarify its role in periodontal diseases.

PMID- 23952076
TI  - Oral administration of all-trans retinoic acid suppresses experimental
      periodontitis by modulating the Th17/Treg imbalance.
AB  - BACKGROUND: A T-helper 17 (Th17)/regulatory T (Treg) imbalance has been suggested
      recently to play a role in the development of periodontitis. All-trans retinoic
      acid (ATRA) has been reported to modulate Th17/Treg imbalances in some diseases.
      However, the effect of ATRA on periodontitis remains unknown. This study observes
      the effect of ATRA on Th17/Treg imbalance modulation in experimental
      periodontitis. METHODS: Experimental periodontitis was induced in mice by oral
      infection with Porphyromonas gingivalis (P. gingivalis). ATRA was orally
      administered every other day. Alveolar bone resorption (ABR) was estimated by
      measuring the distance from the cemento-enamel junction to the alveolar bone
      crest. CD4(+) T-cell subsets in the cervical lymph nodes (CLNs) and spleen were
      analyzed by flow cytometry. Th17/Treg cell-related cytokine messenger ribonucleic
      acid expression was quantified by real-time reverse transcription-polymerase
      chain reaction. RESULTS: The present data shows that ATRA suppressed ABR and
      inhibited inflammatory cell infiltration into periodontal tissues. These effects
      were closely associated with reduced CD4(+) retinoid-related orphan receptor
      gammatau(+) cells and increased CD4(+) forkhead box P3(+) cells in the CLNs.
      Furthermore, ATRA downregulated interleukin (IL)-17A expression and upregulated
      IL-10 and transforming growth factor-beta1 expression in both the CLNs and P.
      gingivalis-infected gingival tissues. CONCLUSIONS: These results suggest that
      ATRA modulation of the Th17/Treg imbalance provides protection against
      periodontitis by enhancing Treg cell activation and inhibiting Th17 cell
      activation. These results indicate the potential for clinical prevention of
      periodontitis.

PMID- 23952077
TI  - Relation of periodontitis and metabolic syndrome with gestational glucose
      metabolism disorder.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) and metabolic syndrome have been
      related to periodontitis. This study's objective is to establish the relationship
      between them in pregnant women affected by gestational glucose metabolism
      disorder. METHODS: In 188 pregnant women with positive O'Sullivan test (POT)
      results, an oral glucose tolerance test (OGTT) was performed to diagnose GDM. The
      mother's periodontal parameters, age, prepregnancy weight and height and body
      mass index (BMI), blood pressure, gestational age, and birth weight were recorded
      at 24 to 28 weeks of pregnancy, as well as levels of glucose, C-reactive protein,
      triglycerides, glycated hemoglobin (HbA1c), and total, low-density lipoprotein,
      high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL)
      cholesterol levels. RESULTS: Prepregnancy weight, prepregnancy BMI, systolic and
      diastolic blood pressure, VLDL cholesterol, and glucose parameters were higher in
      GDM compared with POT (P <0.05). VLDL cholesterol, triglycerides, and 2-hour OGTT
      were higher in patients with periodontitis than in patients without periodontitis
      (P <0.05). HbA1c, triglycerides, and 1- and 2-hour OGTT were positively related
      with probing depth and clinical attachment level; blood glucose was related only
      to bleeding on probing (P <0.05). HbA1c, basal OGTT, and 1- and 2-hour OGTT were
      positively related to prepregnancy BMI and blood pressure; HDL cholesterol was
      negatively related to prepregnancy BMI; C-reactive protein was positively related
      to prepregnancy BMI and diastolic blood pressure (P <0.05). CONCLUSION: These
      data support the relationships among periodontal disease and some biochemical
      parameters such as lipid and glucose data in pregnancy, and also among metabolic
      syndrome and biochemical parameters.

PMID- 23952078
TI  - Solubility of sugars and sugar alcohols in ionic liquids: measurement and PC-SAFT
      modeling.
AB  - Biorefining processes using ionic liquids (ILs) require proper solubility data of
      biomass-based compounds in ILs, as well as an appropriate thermodynamic approach
      for the modeling of such data. Carbohydrates and their derivatives such as sugar
      alcohols represent a class of compounds that could play an important role in
      biorefining. Thus, in this work, the pure IL density and solubility of xylitol
      and sorbitol in five different ILs were measured between 288 and 339 K. The ILs
      under consideration were 1-ethyl-3-methylimidazolium dicyanamide, 1-butyl-3
      methylimidazolium dicyanamide ([bmim][DCA]), Aliquat dicyanamide,
      trihexyltetradecylphosphonium dicyanamide, and 1-ethyl-3-methylimidazolium
      trifluoroacetate. Comparison with the literature data was performed, showing good
      agreement. With the exception of [bmim][DCA], the solubility of these sugar
      alcohols in the other ILs is presented for the first time. The measured data as
      well as previously published solubility data of glucose and fructose in these ILs
      were modeled by means of PC-SAFT using a molecular-based associative approach for
      ILs. PC-SAFT was used in this work as it has shown to be applicable to model the
      solubility of xylitol and sorbitol in ILs (Paduszynski; et al. J. Phys. Chem. B
      2013, 117, 7034-7046). For this purpose, three pure IL parameters were fitted to
      pure IL densities, activity coefficients of 1-propanol at infinite dilution in
      ILs, and/or xylitol solubility in ILs. This approach allows accurate modeling of
      the pure IL data and the mixture data with only one binary interaction parameter
      k(ij) between sugar and the IL or sugar alcohol and the IL. In cases where only
      the pure IL density and activity coefficients of 1-propanol at infinite dilution
      in ILs were used for the IL parameter estimation, the solubility of the sugars
      and sugar alcohols in the ILs could be predicted (k(ij) = 0 between sugar and the
      IL or sugar alcohol and the IL) with reasonable accuracy.

PMID- 23952079
TI  - Fundus autofluorescence imaging in age-related macular degeneration.
AB  - Fundus autofluorescence (FAF) is a noninvasive imaging technology that provides
      information on the distribution of lipofuscin within the retinal pigment
      epithelial cells. Progressive accumulation of lipofuscin within retinal pigment
      epithelial cells is involved in the pathogenesis of age-related macular
      degeneration (AMD). Fundus autofluorescence imaging using a confocal scanning
      laser ophthalmoscope is a useful technique to identify high-risk characteristics
      in patients with nonexudative AMD. It gives also some valuable knowledge and
      clues in differantial diagnosis of exudative age-related macular degeneration.
      This review comprises an introduction to fundus autofluorescence, a review of FAF
      imaging in AMD, and the recent classification of geographic atrophy (GA) and
      early AMD phenotypes by the Fundus Autofluorescence in Age-related Macular
      Degeneration Study. The association of phenotype and atrophy progression and
      choroidal neovascularization development are also summarized.

PMID- 23952080
TI  - Photorefractive keratectomy on purely refractive accommodative esotropia.
AB  - CONTEXT: Results on refractive keratectomy of the treatment of young patients
      with purely refractive accommodative esotropia. AIMS: Evaluating the results of
      refractive keratectomy (PRK) on the treatment of young patients with purely
      refractive accommodative esotropia. METHODS AND MATERIAL: This prospective study
      comprised patients with purely accommodative hyperopic esotropia. Patients
      underwent a complete ophthalmologic examination that included pre-operative and
      post-operative best corrected visual acuity (BCVA) and uncorrected visual acuity
      (UCVA) (at 3, 12, and 24 months), alignment and sensory outcomes; keratometry,
      pachymetry, and corneal topography. STATISTICAL ANALYSIS USED: paired T-student.
      RESULTS: Twenty eyes of 10 patients (mean age 21.5 years) were treated. The pre
      operative mean UCVA was 0.70 logMAR (SD +/- 0.177) and 0.02 logMAR (SD +/- 0.029)
      two years later. The pre-operative BCVA was 0.02 logMAR (SD +/- 0.037) and 0.01
      (SD +/- 0.026) two years later. The mean spherical equivalent (SE) in cyclopegia
      was + 3.92 D (range: +2.75 to +5.00 D; SD = 0.62) pre-operatively, -0.69 D (range
      -0.5 to -1) at three months and 0 D (range: -0.25 to 0.25) at one and two years
      later. After surgery, all patients were orthophoric without correction and
      stereopsis was unaffected by PRK. CONCLUSIONS: A two-year follow-up showed that
      photorefractive keratectomy was an effective treatment for esotropia associated
      with mild to moderate hyperopia in young adults with purely refractive
      accommodative esotropia.

PMID- 23952082
TI  - EURRECA. Foreword.

PMID- 23952083
TI  - EURRECA. Foreword.

PMID- 23952084
TI  - EURRECA-Framework for Aligning Micronutrient Recommendations.
AB  - There is currently no standard approach for deriving micronutrient
      recommendations, and large variations exist across Europe, causing confusion
      among consumers, food producers, and policy makers. More aligned information
      could influence dietary behaviors and potentially lead to a healthier population.
      Funded by the European Commission, EURRECA (EURopean micronutrient
      RECommendations Aligned) has developed methods and applications to guide Nutrient
      Recommendation Setting Bodies through the process of setting micronutrient
      reference values. The EURRECA approach is crystallized into its framework that
      outlines a standard process for deriving and using dietary reference values for
      micronutrients in a transparent, systematic, and scientific way. The 9 activities
      of the framework can be clustered into four stages (i) defining the problem, (ii)
      monitoring and evaluating, (iii) deriving dietary reference values, and (iv)
      using dietary reference values in policy making. The EURRECA framework should not
      be interpreted as a prescriptive description of a linear process, but as a
      structured guide for checking that all issues essential for deriving requirements
      have at least been considered.

PMID- 23952085
TI  - EURRECA-Evidence-based methodology for deriving micronutrient recommendations.
AB  - The EURopean micronutrient RECommendations Aligned (EURRECA) Network of
      Excellence explored the process of setting micronutrient recommendations to
      address the variance in recommendations across Europe. Work centered upon the
      transparent assessment of nutritional requirements via a series of systematic
      literature reviews and meta-analyses. In addition, the necessity of assessing
      nutritional requirements and the policy context of setting micronutrient
      recommendations was investigated. Findings have been presented in a framework
      that covers nine activities clustered into four stages: stage one "Defining the
      problem" describes Activities 1 and 2: "Identifying the nutrition-related health
      problem" and "Defining the process"; stage two "Monitoring and evaluating"
      describes Activities 3 and 7: "Establishing appropriate methods," and "Nutrient
      intake and status of population groups"; stage three "Deriving dietary reference
      values" describes Activities 4, 5, and 6: "Collating sources of evidence,"
      "Appraisal of the evidence," and "Integrating the evidence"; stage four "Using
      dietary reference values in policy making" describes Activities 8 and 9:
      "Identifying policy options," and "Evaluating policy implementation." These
      activities provide guidance on how to resolve various issues when deriving
      micronutrient requirements and address the methodological and policy decisions,
      which may explain the current variation in recommendations across Europe.
      [Supplementary materials are available for this article. Go to the publisher's
      online edition of Critical Reviews in Food Science and Nutrition for the
      following free supplemental files: Additional text, tables, and figures.].

PMID- 23952086
TI  - EURRECA-Estimating folate requirements for deriving dietary reference values.
AB  - In most countries, the dietary folate intake associated with adequate status of
      red cell folate and/or serum folate provides the basis for formulating reference
      values. One of the major challenges in setting dietary reference values for
      folate, however, is the need to account for the differences in bioavailability
      between the natural forms of the vitamin and the synthetic form, folic acid,
      albeit to date, few countries in Europe take bioavailability into consideration.
      A series of systematic reviews that included only those studies which used the
      most robust measures of both folate intake and folate status were carried out by
      the EURRECA Network of Excellence to examine the relationships between folate
      intake, status, and a number of health outcomes relevant to specific stages of
      the lifecycle. This review summarizes the available evidence and the issues to
      consider in the setting of dietary reference values for folate.

PMID- 23952087
TI  - EURRECA-Estimating iodine requirements for deriving dietary reference values.
AB  - Iodine is an essential component of thyroid hormones, and current recommendations
      for intake are based on urinary iodine excretion, assessment of thyroid size,
      thyroidal iodine accumulation and turnover, radioactive iodine uptake, balance
      studies, and epidemiological studies. Dietary iodine is rapidly and almost
      completely absorbed. The prevalence of inadequate iodine intake is high: 29% of
      the world's population lives in iodine-deficient areas and 44% of Europe remains
      mildly iodine deficient. To assess current data and update evidence for setting
      dietary recommendations for iodine, the EURRECA Network of Excellence has
      undertaken systematic review and evaluation of (i) the usefulness of iodine
      status biomarkers (ii) the relationship between iodine status biomarkers and
      dietary iodine intake, and (iii) the relationship between iodine intake and
      health outcomes (endemic goiter, hypothyroidism, and cognitive function). This
      review summarizes the main research outputs: the key findings of the literature
      review, results of the meta-analyses, and discussion of the main conclusions.
      Currently, data for relevant intake-status-health relationships for iodine are
      limited, particularly for population groups such as children under two years,
      pregnant women, and the elderly. The EURRECA Network developed best practice
      guidelines for the identification of pertinent iodine studies based on a
      systematic review approach. This approach aimed to identify comparable data,
      suitable for meta-analysis, for different countries and across all age ranges.
      When new data are available, the EURRECA Network best practice guidelines will
      provide a better understanding of iodine requirements for different health
      outcomes which could be used to set evidence-based dietary iodine recommendations
      for optimal health.

PMID- 23952088
TI  - EURRECA-Estimating iron requirements for deriving dietary reference values.
AB  - Currently, a factorial approach is used to derive reference values for iron.
      Calculations include the use of a bioavailability factor to convert the
      physiological requirement, derived from obligatory losses and requirements for
      growth and development, into a dietary intake value. A series of systematic
      reviews undertaken by the EURRECA Network of Excellence aimed to identify data
      that may increase the accuracy of factorial calculations across all population
      groups. The selection of robust data was guided by the use of standardized review
      methodology and the evidence-based selection of status biomarkers and dietary
      intake assessment techniques. Results corroborated the dearth of relevant
      factorial data, including whole-diet bioavailability data, and confirmed the need
      to continue extrapolating physiological requirements across population groups.
      Data were also unavailable that would allow reference values to be based on
      selected health outcomes associated with iron intake or status. Ideally, a series
      of observational and randomized controlled trial (RCT) studies need to be
      undertaken across all population groups and life stages to generate robust data
      for setting dietary reference values for iron. It will also be essential to
      include information on polymorphisms that potentially influence iron absorption
      and status in the derivation process.

PMID- 23952089
TI  - EURRECA-Estimating selenium requirements for deriving dietary reference values.
AB  - Current reference values for selenium, an essential micronutrient, are based on
      the intake of selenium that is required to achieve maximal glutathione peroxidase
      activity in plasma or erythrocytes. In order to assess the evidence of relevance
      to setting dietary reference values for selenium, the EURRECA Network of
      Excellence focused on systematic searches, review, and evaluation of (i) selenium
      status biomarkers and evidence for relationships between intake and status
      biomarkers, (ii) selenium and health (including the effect of intake and/or
      status biomarkers on cancer risk, immune function, HIV, cognition, and
      fertility), (iii) bioavailability of selenium from the diet, and (iv) impact of
      genotype/single nucleotide polymorphisms on status or health outcomes associated
      with selenium. The main research outputs for selenium and future research
      priorities are discussed further in this review.

PMID- 23952090
TI  - EURRECA-Estimating vitamin D requirements for deriving dietary reference values.
AB  - The time course of the EURRECA from 2008 to 2012, overlapped considerably with
      the timeframe of the process undertaken by the North American Institute of
      Medicine (IOM) to revise dietary reference intakes for vitamin D and calcium
      (published November 2010). Therefore the aims of the vitamin D-related activities
      in EURRECA were formulated to address knowledge requirements that would
      complement the activities undertaken by the IOM and provide additional resources
      for risk assessors and risk management agencies charged with the task of setting
      dietary reference values for vitamin D. A total of three systematic reviews were
      carried out. The first, which pre-dated the IOM review process, identified and
      evaluated existing and novel biomarkers of vitamin D status and confirmed that
      circulating 25-hydroxyvitamin D (25(OH)D) concentrations is a robust and reliable
      marker of vitamin D status. The second systematic review conducted a meta
      analysis of the dose-response of serum 25(OH)D to vitamin D intake from
      randomized controlled trials (RCT) among adults to explore the most appropriate
      model of the vitamin D intake-serum 25(OH)D) relationship to estimate
      requirements. The third review also carried out a meta-analysis to evaluate
      evidence of efficacy from RCT using foods fortified with vitamin D, and found
      they increased circulating 25(OH)D concentrations in a dose-dependent manner but
      identified a need for stronger data on the efficacy of vitamin D-fortified food
      on deficiency prevention and potential health outcomes, including adverse
      effects. Finally, narrative reviews provided estimates of the prevalence of
      inadequate intakes of vitamin D in adults and children from international dietary
      surveys, as well as a compilation of research requirements for vitamin D to
      inform current and future assessments of vitamin D requirements. [Supplementary
      materials are available for this article. Go to the publisher's onilne edition of
      Critical Reviews in Food Science and Nutrion for the following free supplemental
      files: Additional text, tables, and figures.].

PMID- 23952091
TI  - EURRECA-Estimating zinc requirements for deriving dietary reference values.
AB  - Zinc was selected as a priority micronutrient for EURRECA, because there is
      significant heterogeneity in the Dietary Reference Values (DRVs) across Europe.
      In addition, the prevalence of inadequate zinc intakes was thought to be high
      among all population groups worldwide, and the public health concern is
      considerable. In accordance with the EURRECA consortium principles and protocols,
      a series of literature reviews were undertaken in order to develop best practice
      guidelines for assessing dietary zinc intake and zinc status. These were
      incorporated into subsequent literature search strategies and protocols for
      studies investigating the relationships between zinc intake, status and health,
      as well as studies relating to the factorial approach (including bioavailability)
      for setting dietary recommendations. EMBASE (Ovid), Cochrane Library CENTRAL, and
      MEDLINE (Ovid) databases were searched for studies published up to February 2010
      and collated into a series of Endnote databases that are available for the use of
      future DRV panels. Meta-analyses of data extracted from these publications were
      performed where possible in order to address specific questions relating to
      factors affecting dietary recommendations. This review has highlighted the need
      for more high quality studies to address gaps in current knowledge, in particular
      the continued search for a reliable biomarker of zinc status and the influence of
      genetic polymorphisms on individual dietary requirements. In addition, there is a
      need to further develop models of the effect of dietary inhibitors of zinc
      absorption and their impact on population dietary zinc requirements.

PMID- 23952092
TI  - EURRECA-A framework for considering evidence in public health nutrition policy
      development.
AB  - A key step toward developing appropriate evidence-based public health nutrition
      policies is determining exactly how that evidence should be collected and
      assessed. Despite this the extent to which different evidence bases influence
      policy selection is rarely explored. This article presents an epistemological
      framework which offers a range of considerations affecting this process generally
      and with particular implications for both micronutrient requirements and the role
      of behavior in the policy-making process. Qualitative case study data covering 6
      European countries/regions (Czech Republic, Italy, the Netherlands, Nordic
      countries, Poland, and Spain), and three micronutrients (folate, iodine, and
      vitamin D), have been presented to illustrate the relevance of the Framework.

PMID- 23952093
TI  - EURRECA-Principles and future for deriving micronutrient recommendations.
AB  - The EURopean micronutrient RECommendations Aligned (EURRECA) Network of
      Excellence (NoE) explored an approach for setting micronutrient recommendations,
      which would address the variation in recommendations across Europe. Therefore, a
      framework for deriving and using micronutrient Dietary Reference Values (DRVs)
      has been developed. This framework comprises four stages (defining the problem
      monitoring and evaluating-deriving dietary reference values-using dietary
      reference values in policy making). The aim of the present paper is to use this
      framework to identify specific research gaps and needs related to (1) knowledge
      available on specific micronutrients (folate, iodine, iron, selenium, vitamin
      B12, vitamin D, and zinc) and (2) the methodology presented in the framework.
      Furthermore, the paper describes the different outputs that support the process
      like protocols, guidelines, systematic review databases, and peer-reviewed
      publications, as well as the principal routes of dissemination of these outputs
      to ensure their optimal uptake in policy, practice, and research collaborations.
      The importance of ensuring transparency in risk assessment and risk management,
      systematic searching the literature, and taking into account policy options is
      highlighted. [Supplementary materials are available for this article. Go to the
      publisher's online edition of Critical Reviews in Food Science and Nutrition for
      the following free supplemental files: Additional tables.].

PMID- 23952097
TI  - Opioid-sparing effect of intravenous paracetamol after percutaneous
      nephrolithotomy: a double-blind randomized controlled trial.
AB  - PURPOSE: To evaluate meperidine-sparing effect of intravenous (IV) paracetamol in
      patients undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS:
      One hundred patients who underwent PCNL were randomized to paracetamol (n=50) and
      placebo (n=50) groups. Patients received 100 mL of physiologic saline with or
      without 1 g IV paracetamol every 8 hours after PCNL up to 24 hours in the
      paracetamol and placebo groups, respectively. Patients in both groups received
      intramuscular meperidine in case of unrelieved pain. The visual analog scale
      (VAS) was used to evaluate pain intensity scores in the postoperative period.
      Total meperidine consumption, mean VAS score in the first 6 and 24 hours,
      demographic variables, operative variables, and side effects were recorded.
      RESULTS: The mean VAS pain intensity scores at 6 and 24 hours were 50.22 and
      41.32 mm in the paracetamol and 75.29 or 65.5 mm in the placebo group (P<0.001).
      The mean consumed meperidine dose was 54.40 mg and 77.60 mg in the paracetamol
      and placebo groups, respectively (P<0.001). CONCLUSION: In this study, IV
      paracetamol significantly reduced total meperidine consumption and pain intensity
      scores compared with placebo. IV paracetamol can be an effective and safe part of
      multimodal analgesia regimes for postoperative pain management after PCNL.

PMID- 23952098
TI  - The relationship between changes in joint kinematics parameters and
      mechanomyographic signals during non-isometric contraction in human skeletal
      muscle.
AB  - The present study determines the effects of summation of contraction on joint
      kinematics in human ankle and mechanomyography (MMG) signals during non-isometric
      contraction. The excursion and angular velocity of dorsiflexion and eversion were
      measured during several summation profiles during non-isometric contractions. The
      joint kinematics parameters and MMG responses to 1-8 pulses at a constant
      interval of 10 ms were recorded to investigate the effects of different numbers
      of stimuli. In an examination of two-pulse trains with different inter-pulse
      intervals, the joint kinematics parameters and MMG responses to inter-pulse
      intervals of 10-100 ms were recorded from the tibialis anterior muscle. The main
      finding was that facilitating effects of subsequent stimulation were limited to
      angular velocity of eversion during the contribution of a second stimulus,
      suggesting that facilitating effects of second stimulus reflect angular velocity
      but not joint angle excursion. A comparison with MMG signals clarified that MMG
      signals poorly correlate with changes in the joint kinematics parameters
      (excursion and angular velocity) when the inter-pulse intervals or numbers of
      stimuli are increased. These findings will provide useful information for
      assessing the muscle contractile properties with evoked MMG signals during non
      isometric contraction. 

PMID- 23952099
TI  - Management of early stage chronic myeloid leukemia: state-of-the-art approach and
      future perspectives.
AB  - Tyrosin kinase inhibitors (TKI), have dramatically changed the natural history of
      chronic myeloid leukemia (CML) leading to an impressive increase in overall
      survival rates and allowing many CML patients to achieve a close-to-normal life
      expectancy. Unfortunately, there is growing evidence that these drugs are not
      curative, about 30-35% of the patients who receive imatinib become resistant or
      discontinue the drug because of side effects; moreover, 15% of all patients
      become resistant to all TKIs, a condition which represents the biggest challenge
      in CML treatment. Recent progresses in CML stem cell biology have identified new
      agents and therapeutic strategies that can be used to target the CML stem cell
      compartment. These studies have opened new perspectives and have highlighted key
      strategies for treating, and possibly curing, CML in the upcoming years.

PMID- 23952100
TI  - Serial echocardiography in very preterm infants: a pilot randomized trial.
AB  - AIM: To determine whether routine echocardiography increases diagnosis and
      treatment for patent ductus arteriosus (PDA) and whether randomized nondisclosure
      is a feasible strategy for studying PDA management. METHODS: Two-centre, pilot
      randomized, controlled trial. 88 infants with birth weights <=1250 grams and
      gestational ages <=30 weeks were randomized to disclosure or nondisclosure of
      serial echocardiogram findings. Echocardiograms were performed at 3-5 and 7-10
      days of life. The primary outcome was time to regain birth weight. RESULTS: 100%
      of echocardiograms in the disclosure group were disclosed; 16% (echocardiogram
      #1) and 29% (echocardiogram #2) were disclosed in the nondisclosure group. There
      was a statistically nonsignificant decrease in drug therapy for PDA in the
      nondisclosure group (adjusted odds ratio [AOR] 0.56, 95% confidence interval [CI]
      0.24-1.34). There was no difference in time to regain birth weight or in other
      important neonatal outcomes. However, infants in the nondisclosure group were
      more likely to demonstrate appropriate weight loss and then regain birth weight
      within 7-14 days (AOR 2.64, 95% CI 1.08-6.44). CONCLUSION: Randomized
      nondisclosure of echocardiograms is a feasible strategy for evaluation of
      approaches to PDA management in very preterm infants. Avoidance of routine
      echocardiography may reduce drug therapy for PDA without adverse clinical
      effects.

PMID- 23952101
TI  - Association of valdecoxib, a nonsteroidal anti-inflammatory drug, with human
      serum albumin.
AB  - Valdecoxib addition quenches the intrinsic human serum albumin (HSA)
      fluorescence. This allows an evaluation of the drug-protein association. However,
      both the number of binding sites and their affinity for the drug depend upon the
      methodology employed for their evaluation and the employed protein concentration.
      In this work, we measured the effect of valdecoxib on HSA fluorescence yield over
      a wide range of experimental conditions and discuss the validity of the binding
      parameters derived from the different data treatments: Stern-Volmer, Scatchard,
      double logarithmic, quadratic equation, Benesi-Hilderand, and Encinas-Lissi. It
      is proposed that a combination of Encinas-Lissi and Scatchard treatments of the
      data renders the most reliable results. From these data, it is concluded that HSA
      presents three high-affinity binding sites for valdecoxib (K(as) = 4.5 * 10(4) m(
      1)) and several secondary sites of smaller activity.

PMID- 23952102
TI  - Impact of cyclosporine versus tacrolimus on the incidence of de novo malignancy
      following liver transplantation: a single center experience with 609 patients.
AB  - De novo malignancies are a major cause of late death after liver transplantation.
      Aim of the present study was to determine whether use of cyclosporine versus
      tacrolimus affects long-term tumor incidence considering potential confounders.
      De novo malignancies in 609 liver transplant recipients at Munich Transplant
      Centre between 1985 and 2007 were registered. In 1996, the standard
      immunosuppressive regimen was changed from cyclosporine to tacrolimus. Different
      effects of those drugs on long-term tumor incidence were analyzed in multivariate
      analysis. During 3765 patient years of follow-up (median 4.78 years), 87 de novo
      malignancies occurred in 71 patients (mean age 47.5 +/- 13.3 years, mean time
      after liver transplantation 5.7 +/- 3.7 years). The cumulative incidence of de
      novo malignancies was 34.7% for all tumor entities after 15 years as compared to
      8.9% for a nontransplanted population. The most frequent tumors observed were
      nonmelanoma skin cancers (44.83%). Moreover, post-transplant lymphoid disease,
      oropharyngeal cancer (n = 6, 6.9%), upper gastrointestinal tract cancer (n = 4,
      4.6%), lung cancer (n = 4, 4.6%), gynecological malignancies (n = 4, 4.6%), and
      kidney cancer (n = 3, 3.45%) were detected. Multivariate analysis revealed
      recipient age [hazards ratio (HR) 1.06], male gender (HR 1.73), and tacrolimus
      based immunosuppression (HR 2.06) as significant risk factors. Based on those
      results, a tacrolimus-based immunosuppression should be discussed especially in
      older male patients. Whether reducing tacrolimus target levels may reduce the
      risk for de novo malignancies has yet to be determined in prospective trials. 

PMID- 23952103
TI  - Natural variation and artificial selection in four genes determine grain shape in
      rice.
AB  - The size of cultivated rice (Oryza sativa) grains has been altered by both
      domestication and artificial selection over the course of evolutionary history.
      Several quantitative trait loci (QTLs) for grain size have been cloned in the
      past 10 yr. To explore the natural variation in these QTLs, resequencing of grain
      width and weight 2 (GW2), grain size 5 (GS5) and QTL for seed width 5 (qSW5) and
      genotyping of grain size 3 (GS3) were performed in the germplasms of 127
      varieties of rice (O. sativa) and 10-15 samples of wild rice (Oryza rufipogon).
      Ten, 10 and 15 haplotypes were observed for GW2, GS5 and qSW5. qSW5 and GS3 had
      the strongest effects on grain size, which have been widely utilized in rice
      production, whereas GW2 and GS5 showed more modest effects. GS5 showed small
      sequence variations in O. sativa germplasm and that of its progenitor O.
      rufipogon. qSW5 exhibited the highest level of nucleotide diversity. GW2 showed
      signs of purifying selection. The four grain size genes experienced different
      selection intensities depending on their genetic effects. In the indica
      population, linkage disequilibrium (LD) was detected among GS3, qSW5 and GS5. The
      substantial genetic variation in these four genes provides the flexibility needed
      to design various rice grain shapes. These findings provide insight into the
      evolutionary features of grain size genes in rice.

PMID- 23952104
TI  - Menarcheal age of type 1 diabetic Bengali Indian females.
AB  - BACKGROUND: It has been observed that menstrual characteristics are generally
      influenced by lifestyle, socio-cultural and biological factors. AIM: The present
      study examines: (a) variation in menstrual characteristics between Type1 Diabetic
      females of rural and urban adolescents, i.e. the resident status; and (b) whether
      these characteristics can be predicted from various socio-economic, stress
      variables related to place of residence. SUBJECTS AND METHODS: The sample of the
      present study constituted 103T1DM females from West Bengal, a State of India.
      These girls belong to a Bengali-speaking ethnic group. Data on socio-economic
      variables and menstrual characteristics were collected using pretested
      questionnaires. RESULTS: Menstrual irregularity was common in our study
      participants, with age of menarche, but was not associated with current BMI,
      physical activity or insulin dose. CONCLUSIONS: Our study displays that age at
      menarche is delayed in young women with T1DM compared to the concurrent overall
      mean age at menarche in the West Bengal population.

PMID- 23952105
TI  - Successful controlled ovarian stimulation despite elevated hCG levels after first
      trimester abortion in the context of fertility preservation.
AB  - Fertility preservation prior to gonadotoxic chemotherapy by cryopreservation of
      the ovarian tissue and controlled ovarian stimulation can be effective
      immediately after induced abortion in the first trimenon. In a reproductive
      endocrinology and infertility unit of a tertiary care university-based medical
      centre (University Hospital of Heidelberg) a 37-year-old women with breast cancer
      was counseled for fertility preservation. Cryopreservation of ovarian tissue,
      followed by ovarian stimulation for planned intracytoplasmatic sperm injection
      (ICSI), transvaginal oocyte aspiration and cryopreservation of fertilized eggs
      was performed in spite of persistently elevated human chorionic gonadotropin
      (hCG)-levels after induced abortion. Twenty-four fertilized oocytes with a
      fertilization rate of 92% were cryopreserved. Ovarian stimulation and oocyte
      cryopreservation can be successfully performed with good results immediately
      after miscarriage, despite persistent high hCG-levels.

PMID- 23952106
TI  - Mean platelet volume for distinguishing between inherited thrombocytopenias and
      immune thrombocytopenia--response to Beyan.

PMID- 23952107
TI  - Cost-effectiveness of ART restorations in elderly adults: a randomized clinical
      trial.
AB  - BACKGROUND: As the world population ages, the requirement for cost-effective
      methods of treating chronic disease conditions increases. In terms of oral
      health, there is a rapidly increasing number of dentate elderly with a high
      burden of maintenance. Population surveys indicate that older individuals are
      keeping their teeth for longer and are a higher caries risk group. Atraumatic
      Restorative Treatment (ART) could be suitable for patients in nursing homes or
      house-bound elderly, but very little research has been done on its use in adults.
      OBJECTIVES: To compare the cost-effectiveness of ART and a conventional technique
      (CT) for restoring carious lesions as part of a preventive and restorative
      programme for older adults. METHODS: In this randomized clinical trial, 82
      patients with carious lesions were randomly allocated to receive either ART or
      conventional restorations. Treatment costs were measured based on treatment time,
      materials and labour. For the ART group, the cost of care provided by a dentist
      was also compared to the cost of having a hygienist to provide treatment.
      Effectiveness was measured using percentage of restorations that survived after a
      year. RESULTS: Eighty-two patients received 260 restorations, that is, 128 ART
      and 132 conventional restorations. 91.1% of the restorations were on one surface
      only. After a year, 252 restorations were assessed in 80 patients. The average
      cost for ART and conventional restorations was ?16.86 and ?28.71 respectively;
      the restoration survival percentages were 91.1% and 97.7%, respectively. This
      resulted in a cost-effectiveness ratio of 0.18 (ART) and 0.29 (CT). When the cost
      of a hygienist to provide ART was inserted in the analysis, the resulting ratio
      was 0.14. CONCLUSIONS: Atraumatic restorative treatment was found to be a more
      cost-effective alternative to treat older adults after 1 year, compared to
      conventional restorations, especially in out of surgery facilities and using
      alternative workforce such as hygienists. Atraumatic restorative treatment can be
      a useful tool to provide dental care for frail and fearful individuals who might
      not access dental treatment routinely.

PMID- 23952108
TI  - A C-C bonded phenoxyl radical dimer with a zero bond dissociation free energy.
AB  - The 2,6-di-tert-butyl-4-methoxyphenoxyl radical is shown to dimerize in solution
      and in the solid state. The X-ray crystal structure of the dimer, the first for a
      para-coupled phenoxyl radical, revealed a bond length of 1.6055(23) A for the C4
      C4a bond. This is significantly longer than typical C-C bonds. Solution
      equilibrium studies using both optical and IR spectroscopies showed that the Keq
      for dissociation is 1.3 +/- 0.2 M at 20  degrees C, indicating a C-C bond
      dissociation free energy of -0.15 +/- 0.1 kcal mol(-1). Van't Hoff analysis gave
      an exceptionally small bond dissociation enthalpy (BDE) of 6.1 +/- 0.5 kcal mol(
      1). To our knowledge, this is the smallest BDE measured for a C-C bond. This very
      weak bond shows a large deviation from the correlation of C-C bond lengths and
      strengths, but the computed force constant follows Badger's rule. 

PMID- 23952109
TI  - First report of a Chinese PFOS alternative overlooked for 30 years: its toxicity,
      persistence, and presence in the environment.
AB  - This is the first report on the environmental occurrence of a chlorinated
      polyfluorinated ether sulfonate (locally called F-53B, C8ClF16O4SK). It has been
      widely applied as a mist suppressant by the chrome plating industry in China for
      decades but has evaded the attention of environmental research and regulation. In
      this study, F-53B was found in high concentrations (43-78 and 65-112 MUg/L for
      the effluent and influent, respectively) in wastewater from the chrome plating
      industry in the city of Wenzhou, China. F-53B was not successfully removed by the
      wastewater treatments in place. Consequently, it was detected in surface water
      that receives the treated wastewater at similar levels to PFOS (ca. 10-50 ng/L)
      and the concentration decreased with the increasing distance from the wastewater
      discharge point along the river. Initial data presented here suggest that F-53B
      is moderately toxic (Zebrafish LC50-96 h 15.5 mg/L) and is as resistant to
      degradation as PFOS. While current usage is limited to the chrome plating
      industry, the increasing demand for PFOS alternatives in other sectors may result
      in expanded usage. Collectively, the results of this work call for future
      assessments on the effects of this overlooked contaminant and its presence and
      fate in the environment. 

PMID- 23952110
TI  - Scanning angle Raman spectroscopy of poly(3-hexylthiophene)-based films on indium
      tin oxide, gold, and sapphire surfaces.
AB  - Interest in realizing conjugated polymer-based films with controlled morphology
      for efficient electronic devices, including photovoltaics, requires a parallel
      effort to characterize these films. Scanning angle (SA) Raman spectroscopy is
      applied to measure poly(3-hexylthiophene) (P3HT):phenyl-C61-butyric acid methyl
      ester (PCBM)-blend morphology on sapphire, gold, and indium tin oxide interfaces,
      including functional organic photovoltaic devices. Nonresonant SA Raman spectra
      are collected in seconds with signal-to-noise ratios that exceed 80, which is
      possible due to the reproducible SA signal enhancement. Raman spectra are
      collected as the incident angle of the 785 nm excitation laser is precisely
      varied upon a prism/sample interface from approximately 35 to 70 degrees . The
      width of the ~1447 cm(-1) thiophene C?C stretch is sensitive to P3HT order, and
      polymer order varied depending on the underlying substrate. This demonstrates the
      importance of performing the spectroscopic measurements on substrates and
      configurations used in the functioning devices, which is not a common practice.
      The experimental measurements are modeled with calculations of the interfacial
      mean square electric field to determine the distance dependence of the SA Raman
      signal. SA Raman spectroscopy is a versatile method applicable whenever the
      chemical composition, structure, and thickness of interfacial polymer layers need
      to be simultaneously measured. 

PMID- 23952112
TI  - Inaugural editorial.
AB  - No abstract available for this article. 

PMID- 23952113
TI  - Editor'S foreword.
AB  - No abstract available for this article. 

PMID- 23952111
TI  - Comparison of rectal balloon expulsion test in seated and left lateral positions.
AB  - BACKGROUND: Defecatory disorders can be diagnosed by rectal balloon expulsion
      (BE) and anorectal manometry, which are traditionally evaluated in the seated and
      left lateral (LL) positions, respectively. The aims of this study were to compare
      BE in the LL and seated positions and to compare anorectal manometric parameters
      to BE performed in the seated and LL positions. METHODS: 220 women [healthy (62),
      chronic constipation (158)] had anorectal high-resolution manometry and BE,
      summarized by time required (seated position, normal <=60 s) or external traction
      to facilitate expulsion (LL position, normal <=100 g). KEY RESULTS: Balloon
      expulsion results in both positions were either concordant [normal (141) or
      abnormal (32)] or discordant [only LL abnormal (30), only seated abnormal (17)].
      There was modest agreement [kappa = 0.44 (95% CI 0.30-0.57)] between seated and
      LL BE. Compared with subjects with normal BE in both positions, anal pressure
      during simulated evacuation (SE) was higher, and the rectoanal gradient (rectal
      anal pressure) during SE was more negative in the other 3 categories (i.e.,
      abnormal LL only, abnormal seated only, and both abnormal). High anal pressure
      during SE (OR = 1.02, 95% CI 1.00-1.04) and high rectal sensory threshold for
      desire to defecate (OR = 1.01, 95% CI 1.00-1.02) were associated with increased
      risk of abnormal BE in both positions, whereas high rectal pressure during SE (OR
      = 0.96, 95% CI 0.93-0.98) was associated with lower risk. CONCLUSIONS &
      INFERENCES: There is modest agreement between rectal BE in LL and seated
      positions. In addition to abnormal seated BE, which is considered indicative of
      pelvic floor dysfunction, high resolution manometry findings suggest that even
      some patients with abnormal BE in the LL position have pelvic floor dysfunction.

PMID- 23952114
TI  - Occupational therapy in health care.
AB  - Social critics have been writing with increasing frequency about the dramatic
      changes that we are beginning to experience in our society. Economic, political,
      scientific/technical and social forces are all combining to reshape and
      restructure our world. Many traditional institutions will change in response to
      these transformations in society. In particular, the health care system as we
      know it today is expected to be radically different by the end of this decade.
      This paper presents a view of the future of health care as specialists move from
      a mechanistic, cause-effect orientation to a systems view of human problems.
      Occupational therapy's readiness and willingness to assume new roles in patient
      care is evaluated. Finally, strategies for dealing with new clinical puzzles are
      discussed. 

PMID- 23952115
TI  - The forensic model of occupational therapy.
AB  - In the past decade attorneys have increasingly sought the services of
      occupational therapists to serve as experts in legal and quasi-legal personal
      injury proceedings. This emerging specialty area of forensic practice is rapidly
      developing. The unique qualifications of the therapist enables him to assess and
      document functional assets and deficits of the individual and relate them to
      daily life tasks. This ability makes the occupational therapist an important
      expert on the forensic panel. The therapist provides reports and information to
      persons who are responsible for applying the law, but who are without medical
      backgrounds and therefore do not understand the problems or lack of problems
      which an injured person has in meeting the physical demands of work and daily
      life. Common proceedings in which the occupational therapist's expertise is
      called for include Social Security disability and Workman's Compensation hearings
      and personal injury litigation. The complementary group of forensic experts, of
      which the occupational therapist is one, frequently consists of physician,
      psychologist, vocational expert and economist. Information is provided through
      verbal and written reports as well as through testimony. 

PMID- 23952116
TI  - Community college gerontology education.
AB  - Occupational therapists have the knowledge and skill in principles of geriatric
      health care to qualify them to bring occupational therapy perspectives to
      curriculums in the community colleges. This article gives an account of how one
      therapist who had specialized training in gerontology and a background in nursing
      has been using her skills in a community college. An overview of one course
      entitled, Leisure Program Planning, illustrates the particular relevance of
      occupational therapy background and the understanding of role and the multiple
      factors impinging on individual role enactment to teaching about leisure activity
      and aging. 

PMID- 23952117
TI  - Deinstitutionalizing the occupational therapist.
AB  - This paper will discuss the problems behind the lack of occupational therapists
      working in the community. The paper will also describe a strategy used by a
      professional group in Portland, Oregon to increase the employment of occupational
      therapists in the community mental health field. This is not a research report
      but a description of a problem and of one way it was approached and solved. While
      this paper is concerned primarily with service delivery in the mental health
      arena, it is felt that the problems presented and the strategy for their
      resolution apply equally to other areas of practice in occupational therapy. It
      is the author's contention that with changing health care patterns occupational
      therapists in all areas of practice need to focus job search efforts more in
      community settings rather than in the traditional occupational therapy 'clinic'
      within hospitals and other residential institutions. 

PMID- 23952118
TI  - The horse as a modality for occupational therapy.
AB  - The purpose of this paper is to discuss the use of a horse as a therapeutic
      activity in the treatment of persons with physical disabilities. Occupational
      therapists have traditionally used goal-directed activities for treatment to
      achieve for patient gains in functional independence, both in specific
      dysfunctions and in the holistic manner of the patient interacting with the
      environment. The motivation of the patient to partake actively in the therapy is
      seen as a significant factor in the outcome of treatment. Hippotherapy involves
      the active participation of the patient in specifically prescribed activities
      with goal-directed results. The horse and the riding ring provide a non
      traditional setting which can increase motivation of the patient and be ideal for
      the development of perceptual-motor coordination and sensory integration. The
      effective treatment of physical dysfunction using a horse to facilitate positive
      functional changes in patients will be discussed. 

PMID- 23952119
TI  - Humor as an adjunct to occupational therapy interactions.
AB  - Although humor and laughter have been a natural part of human life in all
      cultures as far back as recorded history can determine, the conscious use of
      humor as a therapeutic technique is comparatively recent. This article suggests
      that health specialists have been slow to adopt the ideas of some of the better
      known researchers and writers in the field due to professional and cultural
      attitudes toward humor as a "frivolous" subject. As more information on the
      positive benefits of humor and laughter is being disseminated in books and
      workshops, previous myths regarding humor are being dispelled and attitudes are
      changing. A brief history of the state of the art over the past decade is
      included along with a few ideas from seminars and workshops on the use of humor
      as a planned activity in health and educational settings. 

PMID- 23952120
TI  - Occupational therapists in the interdisciplinary team setting.
AB  - The interdisciplinary team approach to patient care provides an answer to the
      fragmentation and confusion patients feel when dealing with our complex
      healthcare system. Even though the team approach has been in use for the past two
      decades, implementation of a successful team is very difficult and rarely
      sustained over a significant period of time. This is especially true in general
      hospitals and in physical rehabilitation programs that spring from general
      hospitals where the physician and the nurse are the traditional care group.
      Occupational therapists, as they establish roles on interdisciplinary teams as
      staff members and team leaders, will require a knowledge of what makes a team
      function effectively. They can use this knowledge to evaluate the status of their
      own team and contribute to changes that will insure its long-term success. Six
      key issues should be addressed during the planning stage of any new healthcare
      team to insure its continued viability. These issues are: program philosophy,
      client focus, role clarification, collaboration and information sharing, policies
      and procedures, and staff supportiveness. 

PMID- 23952122
TI  - Issues and trends in mental health practice.
AB  - The issues and trends in federal, state and local jurisdictions currently
      affecting mental health services are reviewed. Implications for roles, services,
      settings, staffing and administration are drawn. The effects on occupational
      therapists working in mental health are described. Finally some predictions are
      made about the future of mental health services in the United States. 

PMID- 23952121
TI  - Occupational therapist.
AB  - The purpose of this paper is to demonstrate the application of the skills of the
      occupational therapist in a position as coordinator of a special vocational
      training program in a community college district. Duties described include
      program for limited-English-proficient adults. A major reason for a specialized
      educational approach for limited-English-speaking adults came from the large
      influx of non-native English speaking immigrants and refugees into the community
      college district, many of them without job skills. The resulting vocational
      linguistic program involves counseling, job-skill training and vocational English
      instruction. A summary of the procedures involved in evaluating language
      proficiency and vocational skills from enrollment to job-ready status is
      presented and explained. This role of the occupational therapist follows the
      trend to incorporate the generic skills of occupational therapy into new areas of
      practice. 

PMID- 23952123
TI  - The challenge of the future to an occupational therapist.
AB  - No abstract available for this article. 

PMID- 23952124
TI  - Forthcoming in occupational therapy in health care.
AB  - No abstract available for this article. 

PMID- 23952125
TI  - Ecological determinants of mating system within and between three Fagus sylvatica
      populations along an elevational gradient.
AB  - Studies addressing the variation of mating system between plant populations
      rarely account for the variability of these parameters between individuals within
      populations, although this variability is often non-negligible. Here, we propose
      a new direct method based on paternity analyses (Mixed Effect Mating Model) to
      estimate individual migration (mi ) and selfing rates (si ) together with the
      pollen dispersal kernel. Using this method and the KINDIST approach, we
      investigated the variation of mating system parameters within and between three
      populations of Fagus sylvatica along an elevational gradient. Among the mother
      trees, si varied from 0% to 48%, mi varied from 12% to 86% and the effective
      number of pollen donors (Nepi ) varied from 2 to 364. The mating patterns
      differed along the gradient, the top population showing higher m and lower s, and
      a trend to higher Nep than the bottom populations. The phenological lag shaped
      long-distance pollen flow both within population (by increasing mi at mother-tree
      level) and between populations (by increasing m at high elevation). Rather than
      the mate density, the canopy density was detected as a major mating system
      determinant within population; it acted as a barrier to pollen flow, decreasing
      the proportion of long-distance pollen flow and increasing si . Overall, the
      effects of ecological factors on mating system were not the same within vs.
      between populations across the gradient, and these factors also differed from
      those traditionally found to shape variation at range-wide scale, highlighting
      the interest of multiscale approaches. 

PMID- 23952126
TI  - Carrier control of MoS2 nanoflakes by functional self-assembled monolayers.
AB  - Carrier doping of MoS2 nanoflakes was achieved by functional self-assembled
      monolayers (SAMs) with different dipole moments. The effect of SAMs on the charge
      transfer between the substrates and MoS2 nanoflakes was studied by Raman
      spectroscopy, field-effect transistor (FET) measurements, and Kelvin probe
      microscope (KFM). Raman data and FET results verified that
      fluoroalkyltrichlorosilane-SAM with a large positive dipole moment, acting as
      hole donors, significantly reduced the intrinsic n-doping characteristic of MoS2
      nanoflakes, while 3-(trimethoxysilyl)-1-propanamine-SAMs, acting as electron
      donors, enhanced the n-doping characteristic. The additional built-in electric
      field at the interface between SiO2 substrates and MoS2 nanoflakes induced by
      SAMs with molecular dipole moments determined the charge transfer process. KFM
      results clearly demonstrated the charge transfer between MoS2 and SAMs and the
      obvious interlayer screening effect of the pristine and SAM-modified MoS2
      nanoflakes. However, the KFM results were not fully consistent with the Raman and
      FET results since the externally absorbed water molecules were shown to partially
      shield the actual surface potential measurement. By eliminating the contribution
      of the water molecules, the Fermi level of monolayer MoS2 could be estimated to
      modulate in a range of more than 0.45-0.47 eV. This work manifests that the work
      function of MoS2 nanoflakes can be significantly tuned by SAMs by virtue of
      affecting the electrostatic potential between the substrates and MoS2 nanoflakes.

PMID- 23952127
TI  - In-stream attenuation of neuro-active pharmaceuticals and their metabolites.
AB  - In-stream attenuation was determined for 14 neuro-active pharmaceuticals and
      associated metabolites. Lagrangian sampling, which follows a parcel of water as
      it moves downstream, was used to link hydrological and chemical transformation
      processes. Wastewater loading of neuro-active compounds varied considerably over
      a span of several hours, and thus a sampling regime was used to verify that the
      Lagrangian parcel was being sampled and a mechanism was developed to correct
      measured concentrations if it was not. In-stream attenuation over the 5.4-km
      evaluated reach could be modeled as pseudo-first-order decay for 11 of the 14
      evaluated neuro-active pharmaceutical compounds, illustrating the capacity of
      streams to reduce conveyance of neuro-active compounds downstream. Fluoxetine and
      N-desmethyl citalopram were the most rapidly attenuated compounds (t1/2 = 3.6 +/-
      0.3 h, 4.0 +/- 0.2 h, respectively). Lamotrigine, 10,11,-dihydro-10,11,-dihydroxy
      carbamazepine, and carbamazepine were the most persistent (t1/2 = 12 +/- 2.0 h,
      12 +/- 2.6 h, 21 +/- 4.5 h, respectively). Parent compounds (e.g., buproprion,
      carbamazepine, lamotrigine) generally were more persistent relative to their
      metabolites. Several compounds (citalopram, venlafaxine, O-desmethyl-venlafaxine)
      were not attenuated. It was postulated that the primary mechanism of removal for
      these compounds was interaction with bed sediments and stream biofilms, based on
      measured concentrations in stream biofilms and a column experiment using stream
      sediments. 

PMID- 23952128
TI  - Synthesis of trans-2-(trifluoromethyl)cyclopropanes via Suzuki reactions with an
      N-methyliminodiacetic acid boronate.
AB  - trans-2-(Trifluoromethyl)cyclopropylboronic acid N-methyliminodiacetic acid
      (MIDA) ester 5 was synthesized as a pure diastereomer from vinylboronic acid MIDA
      ester and (trifluoromethyl)diazomethane in a single step. An X-ray study
      confirmed the trans-stereochemistry around the cyclopropyl ring. Use of 5 in
      Suzuki reactions, with a variety of aryl or heteroaryl coupling partners,
      provided trans-2-(trifluoromethyl)cyclopropyl products in moderate to excellent
      yields (17-90%). 

PMID- 23952130
TI  - Impact of remaining zinc oxide-eugenol-based sealer on the bond strength of a
      resinous sealer to dentine after root canal retreatment.
AB  - AIM: To evaluate the bond strength of a resin-based sealer (AH Plus) to root
      canal dentine after the removal of a zinc oxide-eugenol-based sealer (Endofill),
      using different retreatment techniques. METHODOLOGY: The root canals of sixty
      four maxillary incisors were prepared with ProTaper and filled with
      Endofill/gutta-percha. After thermocycling, the roots were randomly assigned
      according to the retreatment technique (n = 16): (A) ProTaper, (B)
      ProTaper/xylol, (C) ultrasound and (D) ultrasound/xylol and according to whether
      an operating microscope (OM) was used or not (n = 8): GI- direct vision (DV) and
      GII- indirect through the OM. Eight additional roots were instrumented and filled
      with AH Plus/gutta-percha (control). Roots were sectioned to obtain 1-mm-thick
      slices. Slices were used in the push-out test and in confocal microscopy. Data
      were submitted to anova and Tukey test (alpha = 0.05). RESULTS: The specimens
      filled under the OM (2.50 +/- 0.90) had higher bond strength values of sealer to
      root canal walls (P < 0.05). The control group had superior mean adhesion values
      (4.75 +/- 1.47) that were significantly different from the others (P < 0.05).
      Ultrasound/xylol (2.53 +/- 1.00) was superior to ultrasound (2.23 +/- 0.72) (P <
      0.05), ProTaper (2.20 +/- 0.69), ProTaper/Xylol (2.12 +/- 0.65), which were
      similar (P > 0.05). Bond strength was different in all thirds (P < 0.05) and
      decreased in the following sequence: cervical (3.19 +/- 1.18), middle (2.58 +/-
      1.21) and apical (1.87 +/- 0.68). Confocal analysis revealed residues of Endofill
      in dentinal tubules when the removal protocol was carried out with ProTaper, but
      not from ultrasound combined with xylol. CONCLUSIONS: The OM was associated with
      higher bond strength values for filling material to root canals. The zinc oxide
      eugenol-based sealer negatively affected the bond strength of AH Plus to root
      canal walls, regardless of the retreatment technique.

PMID- 23952131
TI  - The case for routine maintenance of dental implants.
AB  - The large majority of dental implants are successful over the long term. Failure
      is usually associated with infection, trauma, inflammation, or a combination of
      these factors. Early identification and appropriate treatment can identify and
      eliminate these problems in the majority of cases. Thus routine implant
      maintenance structured along the guidelines for patients with periodontal
      diseases is recommended. 

PMID- 23952132
TI  - Presentation of suspected pediatric uveitis.
AB  - Presentation of suspected pediatric uveitis: Pediatric uveitis is usually managed
      in specialized ophthalmic centers in the UK. Meaningful data acquisition in these
      clinics may be helpful in clinical governance, and healthcare planning in a
      specialty that is gradually changing due to changes in treatment choices.
      METHODS: Retrospective analysis of prospectively acquired data in the Liverpool
      pediatric uveitis database was performed. RESULTS: Analysis of our data, based on
      147 patients, with a mean age of 10 years, indicated a female to male ratio of
      2:1. 99% of patients were Caucasian. Our data indicates 86% of all patients
      attending the uveitis clinic were diagnosed with juvenile idiopathic arthritis,
      followed by intermediate uveitis 5% and idiopathic uveitis 4%. 46% of patients
      required treatment. Systemic treatment included methotrexate (34%), prednisolone
      (14%), etanercept (6%), ciclosporin (6%), mycophenolate (3%), and infliximab
      (1%). Severe visual loss (defined by counting fingers or below vision) was seen
      in 10 eyes despite appropriately treated chronic uveitis. CONCLUSION: Our data
      shows uveitis-related ocular morbidity in a predominantly pediatric Caucasian
      population. Patients with severe and chronic uveitis may experience significant
      uveitis-related complications and subsequent visual loss despite aggressive
      treatment.

PMID- 23952133
TI  - Compatibility of spectacles with their prescriptions in central Anatolia.
AB  - PURPOSE: To investigate compatibility of spectacles with their prescriptions.
      METHODS: This study was conducted prospectively between October 2007 and March
      2009. A total of 1002 spectacles of 1002 individuals were included in the study.
      First right and then left lenses of the spectacles were measured with a Topcon CL
      200 digital lensmeter. Interpupillary distance (PD) of the subjects was measured.
      Spherical, cylindrical, and axial differences between the prescription and the
      spectacles were separately calculated for the left and right lenses. Prismatic
      effect (PE) of the lenses, with decentralized focus according to the pupil, its
      base direction, and amount of decentralization, were measured. RESULTS: A total
      of 505 (50.4%) of the subjects were female and 497 (49.6%) were male. The mean
      age was 37.0 (range 3-81). The mean PD of the subjects was 59.9 +/- 4.09 mm, and
      mean optical center distance (OCD) of the lenses was 65.6 +/- 4.07 mm. The
      difference between PD and OCD was significant (p < 0.001). While the right
      spherical, cylindrical, and axial differences and left spherical, cylindrical,
      and axial differences between the prescription and the spectacles were not
      significant, the left axial difference was statistically significant (p < 0.001).
      The decentralization direction was towards the lower temporal with a percentage
      of 76.8% on the right and 80.3% on the left lenses. The mean amount of the
      decentralization was 4.37 +/- 2.39 mm on the right and 4.63 +/- 2.36 mm on the
      left. CONCLUSION: Dioptric error in the spectacles was quite low. However, there
      may be a small amount of axis deviation at the time of mounting the lens to the
      frame. We conclude that asthenopic complaints due to PE caused by the
      decentralization of the optic center of the lenses are quite important.
      Examination of the spectacles after they are prepared can be deemed as a solution
      to reduce asthenopic complaints due to improper spectacles.

PMID- 23952134
TI  - Recurrent subdural hygromas after foramen magnum decompression for Chiari Type I
      malformation.
AB  - A paediatric case of foramen magnum decompression for Chiari Type I malformation
      complicated by recurrent subdural hygromas (SH) and raised intracranial pressure
      without ventriculomegaly is described. SH pathogenesis is discussed, with
      consideration given to arachnoid fenestration. We summarise possibilities for
      treatment and avoidance of this unusual consequence of foramen magnum
      decompression.

PMID- 23952135
TI  - Third ventricular cavernous malformation: an unusual lesion.
AB  - Cavernomas constitute 5-10% of all the vascular malformations of the CNS. They
      commonly present during the 2nd and 5th decades of life. Intraventricular
      cavernomas constitute rare pathological entity, constituting 2.5-10.8% of
      cerebral cavernomas. (1) The natural history of intraventricular cavernomas
      remains undefined to some extent. Those in third ventricle are different in
      biological nature and need more aggressive therapy. These cavernomas appear to
      have the ability to grow very rapidly, resulting in significant morbidity. It is
      not known whether waiting after acute hemorrhage from an intraventricular
      cavernoma improves our ability to remove the lesion safely or if waiting
      unnecessarily increases the risk of hydrocephalus, additional bleeding, or
      further lesion growth.

PMID- 23952136
TI  - Analysis of risk factors for chronic subdural haematoma recurrence after burr
      hole surgery: optimal management of patients on antiplatelet therapy.
AB  - OBJECTIVE. Not much is known about surgical management of patients with chronic
      subdural haematoma (CSDH) treated with antiplatelet or anticoagulant therapy. The
      aims of this study were to review the surgical outcomes of patients with CSDH and
      assess the risks of antiplatelet in their surgical management. METHODS. We
      retrospectively analysed 448 consecutive patients with CSDH treated by one burr
      hole surgery at our institution. Among them, 58 patients had been on antiplatelet
      therapy. We discontinued the antiplatelet agents before surgery for all 58
      patients. For 51 of these 58 patients (87.9%), early surgery was performed within
      0-2 days from admission. We analysed the association between recurrence and
      patient characteristics, including history of antiplatelet or anticoagulant
      therapy; age (< 70 years or >= 70 years); side; history of angiotensin receptor
      II blocker, angiotensin converting enzyme blocker, or statin therapy; and
      previous medical history of head trauma, infarction, hypertension, diabetes
      mellitus, haemodialysis, seizure, cancer, or liver cirrhosis. RESULTS. Recurrence
      occurred in 40 patients (8.9%), which was one of the lowest rates in the
      literature. Univariate analysis showed that only the presence of bilateral
      haematomas was associated with increased recurrence rate while antiplatelet or
      anticoagulant therapy did not significantly increase recurrence risk. Also, the
      recurrence rate from early surgery (0-2 days from drug cessation) for patients on
      antiplatelet therapy was not significantly higher than that from elective surgery
      (5 days or more after drug cessation). However, multivariate analysis revealed
      that previous history of cerebral infarction was an independent risk factor for
      CSDH recurrence. CONCLUSIOns. Our overall data support the safety of early
      surgery for patients on the preoperative antiplatelet therapy without drug
      cessation or platelet infusion. Patients with a previous history of infarction
      may need to be closely followed regardless of antiplatelet or anticoagulant
      therapy.

PMID- 23952137
TI  - Lipid-lowing pharmacogenomics in Chinese patients.
AB  - Pharmacogenomic studies on statins ranging from the candidate gene approach to
      the genome-wide studies in western populations have provided evidence that
      genetic variations play a limited role in determining statin responses. However,
      there are ethnic difference in the pharmacokinetics and safety of statins and due
      to the different frequencies of polymorphisms and different linkage
      disequilibrium patterns among the ethnic groups, the genetic markers identified
      in genome-wide association study platforms or in candidate gene studies in one
      population cannot always be generalized to other populations. This review
      provides an overview on the pharmacogenomics of statins in Chinese population.

PMID- 23952138
TI  - Integral method (IM) as a quantitative and objective method to supplement the
      GMFCS classification of gait in children with cerebral palsy (CP).
AB  - Gait analysis is an objective tool for the clinical assessment of locomotor
      activity in children with cerebral palsy (CP). Correct diagnosis and properly
      planned rehabilitation are necessary for enhanced motor functions in persons
      suffering from cerebral palsy. Orthoses, orthopedic operations, medications and
      physiotherapy are the most common treatments. However, there is still a lack of
      objective methods for assessing motor behavior and monitoring the progress of
      recovery. The aim of the study was to use the ground reaction force patterns
      generated during walking to create the Integral Method (IM), which could become
      an objective tool that could supplement the functional classification of CP
      children based on the Gross Motor Function Classification System (GMFCS). A total
      of 15 healthy children and 34 children with CP who walk independently
      participated in the study. A Kistler force plate and GRFintegral software were
      used. Of the 34 measurements based on the IM for CP children, 17 matched the
      level assigned by the GMFCS, 2 children were assigned a higher level, and 15 were
      assigned a lower level. Pearson's correlation coefficient between the IM and the
      GMFCS was moderate (r = 0.61, p <= 0.01). Asymmetry was found in 11 cases. The IM
      supplements the GMFCS and is an objective and quantitative assessment of motor
      abilities. The method allows for the detection of asymmetry, diagnosis of the
      improvement of gait pattern and assessment of foot support technique. With the
      appropriate software, the IM provides pediatricians, neurologists, orthopedists,
      surgeons and physiotherapists with a simple and fast way to assess gait. 

PMID- 23952139
TI  - The promise of neuroanatomical markers in psychosis.

PMID- 23952140
TI  - Reply to: 'passive smoking increases pain perception in children undergoing
      venous catheterization'.

PMID- 23952141
TI  - Severe fatigue after kidney transplantation: a highly prevalent, disabling and
      multifactorial symptom.
AB  - Fatigue is a common symptom of patients with chronic kidney disease, but seldom
      investigated after transplantation. We determined the prevalence, impact and
      related factors of severe fatigue in kidney transplant recipients (KTRs). Medical
      records and questionnaires were used to assess kidney function, donor
      characteristics, fatigue (Checklist Individual Strength), functional impairments
      (Sickness Impact Profile), work status, body mass index (BMI), pain, depressive
      symptoms, social support and sleeping problems in 180 participating KTRs. KTRs
      were compared with sex- and age-matched population-based controls. KTRs were
      significantly more often severely fatigued (39%) compared to matched controls
      (22%; P = 0.001). Severely fatigued KTRs had significantly more functional
      impairments than nonseverely fatigued recipients (effect size >= 0.7) P < 0.001,
      and less often a paid job (27% vs. 48%, P = 0.005). Univariate analysis showed
      that severely fatigued KTRs received more often a kidney from a deceased donor,
      had a higher BMI, more pain, discrepancy in social support, depressive symptoms
      and sleeping problems. In a multivariate analysis (n = 151) the latter two
      associations remained significant. Severe fatigue is a highly prevalent and
      disabling symptom in KTRs. Moreover, severe fatigue after kidney transplantation
      is more strongly related to behavioural and psychosocial factors than specific
      transplantation-related factors. Findings have implications for fatigue
      management. 

PMID- 23952142
TI  - Paternal leakage, heteroplasmy, and the evolution of plant mitochondrial genomes.
AB  - Plant mitochondrial genomes are usually transmitted to the progeny from the
      maternal parent. However, cases of paternal transmission are known and are
      perhaps more common than once thought. This review will consider recent evidence,
      both direct and indirect, of paternal transmission (leakage) of the mitochondrial
      genome of seed plants, especially in natural populations, and how this can result
      in offspring that carry a mixture of maternally and paternally derived copies of
      the genome; a type of heteroplasmy. It will further consider how this
      heteroplasmy facilitates recombination between genetically distinct partners; a
      process that can enhance mitochondrial genotypic diversity. This will then form
      the basis for a discussion of five evolutionary questions that arise from these
      observations. Questions include how plant mitochondrial genome evolution can be
      placed on a sexual to asexual continuum, whether cytoplasmic male sterility (CMS)
      facilitates the evolution of paternal leakage, whether paternal leakage is more
      likely in populations undergoing admixture, how leakage influences patterns of
      gene flow, and whether heteroplasmy occurs in natural populations at a frequency
      greater than predicted by crossing experiments. It is proposed that each of these
      questions offers fertile ground for future research on a diversity of plant
      species.

PMID- 23952143
TI  - Biosimilars: current scientific and regulatory considerations.
AB  - The widespread use of biologics has paved way for newer options in therapeutics
      for once incurable illnesses. Their large and complex protein structure, post
      translational modifications, elaborate manufacturing/production process and risk
      for immunogenicity adds to the uniqueness of a biologic product. Patent
      expiration of innovator biologics has led to the development of biosimilars;
      biologics similar /comparable to the reference product in terms of quality,
      safety and efficacy. We discuss the clinical safety and regulatory requirements
      for biosimilars in various countries across the world. Future holds promise for
      biosimilars to provide affordable, efficacious and safe treatment to a vast
      majority of patients with significant cost savings to the nation.

PMID- 23952144
TI  - Gene expression analysis of the Brazilian type of hereditary persistence of fetal
      hemoglobin: identification of genes that could be related to gamma-globin
      activation.
AB  - Increased gamma-globin production and consequent fetal hemoglobin (Hb F,
      alpha2gamma2) formation is an important modulator of the clinical and
      hematological features of hemolytic anemias, such as sickle cell disease and beta
      thalassemia (beta-thal). Hb F genes are genetically regulated, but despite
      numerous studies, the molecular basis of hemoglobin (Hb) switching is not
      completely understood. Hereditary persistence of fetal Hb (HPFH) is a consequence
      of impaired switching in adult life, which results in the continued expression of
      the gamma-globin gene. This study was undertaken to identify genes that could be
      involved in Hb switching and/or maintenance of elevated Hb F levels. Two
      libraries were constructed using reticulocytes from normal donors and from
      Brazilian HPFH subjects. Results suggest that the maintenance of Hb F levels
      could be associated with some gene/protein expression modifications, such as low
      expression of KLF1, a transcription factor known to contribute to the regulation
      and modulation of Hb switching, decreased expression of MIER1, known for the
      recruitment of chromatin remodeling enzymes, and decreased expression of HOOK3.
      These data suggest new genes that may play a role in globin gene regulation,
      gamma-globin gene expression and augmentation of Hb F levels, and may represent
      newly-defined cellular pathways for the control of Hb switching in erythroid
      cells. 

PMID- 23952146
TI  - Dentist-specific variation in diagnosis of caries - a multilevel analysis.
AB  - BACKGROUND: There are few studies on practice variation within dentistry. This
      contrasts with medicine where numerous studies exist. A major finding from the
      field of medicine is that the size of the physician-specific effects depends on
      the degree of uncertainty in diagnosis. The physician-specific effects are small
      for diseases where the diagnostic criteria are unambiguous. Conversely, the
      effects are large for diseases where the diagnostic criteria are less
      unambiguous. OBJECTIVES: To assess the size of provider-specific variation in the
      diagnosis of caries among children and adolescents in Norway and to determine
      whether this variation depends on uncertainty in diagnosis. METHODS: Data on
      caries diagnosis for 709 611 children and adolescents aged 6-18 years were
      analysed using multilevel regression. Level-1 was patients and level-2 was public
      dental officers and dental hygienists. Caries was measured according to the
      following localization of the lesion: in the outer half of the enamel, in the
      inner half of the enamel, in the outer third of the dentine, in the middle and
      inner third of the dentine, to the pulp. The degree of uncertainty in diagnosis
      is expected to be least the deeper into the dentine the lesion goes. Our sample
      included 87.5% of all individuals aged 6-18 years. RESULTS: The provider-specific
      variation, measured as the intraclass correlation coefficient, ranged from 15%
      for caries lesions localized in the outer half of the enamel to 2% for caries to
      the pulp. CONCLUSIONS: The size of provider-specific variation in the diagnosis
      of caries is fairly low. The size of the variability is dependent on the level of
      diagnostic uncertainty, which is coherent with the practice style hypothesis.

PMID- 23952145
TI  - Acute chest syndrome is associated with single nucleotide polymorphism-defined
      beta globin cluster haplotype in children with sickle cell anaemia.
AB  - Genetic diversity at the human beta-globin locus has been implicated as a
      modifier of sickle cell anaemia (SCA) severity. However, haplotypes defined by
      restriction fragment length polymorphism sites across the beta-globin locus have
      not been consistently associated with clinical phenotypes. To define the genetic
      structure at the beta-globin locus more thoroughly, we performed high-density
      single nucleotide polymorphism (SNP) mapping in 820 children who were homozygous
      for the sickle cell mutation (HbSS). Genotyping results revealed very high
      linkage disequilibrium across a large region spanning the locus control region
      and the HBB (beta-globin gene) cluster. We identified three predominant
      haplotypes accounting for 96% of the beta(S) -carrying chromosomes in this
      population that could be distinguished using a minimal set of common SNPs.
      Consistent with previous studies, fetal haemoglobin level was significantly
      associated with beta(S) -haplotypes. After controlling for covariates, an
      association was detected between haplotype and rate of hospitalization for acute
      chest syndrome (ACS) (incidence rate ratio 0.51, 95% confidence interval 0.29
      0.89) but not incidence rate of vaso-occlusive pain or presence of silent
      cerebral infarct (SCI). Our results suggest that these SNP-defined beta(S) 
      haplotypes may be associated with ACS, but not pain or SCI in a study population
      of children with SCA. 

PMID- 23952147
TI  - Mechanistic insights and kinetic analysis for the oxidative hydroxylation of
      arylboronic acids by visible light photoredox catalysis: a metal-free
      alternative.
AB  - The photocatalytic hydroxylation of boronic acids with methylene blue as
      photosensitizer proceeds with high efficiency. Detailed time-resolved studies of
      the relevant rate constants provide a clear mechanistic understanding of excited
      state processes and guided the selection of the photocatalyst and the
      optimization of experimental conditions. 

PMID- 23952150
TI  - From the editor's desk.
AB  - No abstract available for this article. 

PMID- 23952149
TI  - Droplet evaporation dynamics on a superhydrophobic surface with negligible
      hysteresis.
AB  - We report on experiments of droplet evaporation on a structured superhydrophobic
      surface that displays very high contact angle (CA ~ 160 deg), and negligible
      contact angle hysteresis (<1 deg). The droplet evaporation is observed to occur
      in a constant-contact-angle mode, with contact radius shrinking for almost the
      entire duration of evaporation. Experiments conducted on Teflon-coated smooth
      surface (CA ~ 120 deg) as a baseline also support an evaporation process that is
      dominated by a constant-contact-angle mode. The experimental results are compared
      with an isothermal diffusion model for droplet evaporation from the literature.
      Good agreement is observed for the Teflon-coated smooth surface between the
      analytical expression and experimental results in terms of the total time for
      evaporation, transient volume, contact angle, and contact radius. However, for
      the structured superhydrophobic surface, the experiments indicate that the time
      taken for complete evaporation of the droplet is greater than the predicted time,
      across all droplet volumes. This disparity is attributed primarily to the
      evaporative cooling at the droplet interface due to the high aspect ratio of the
      droplet and also the lower effective thermal conductivity of the substrate due to
      the presence of air gaps. This hypothesis is verified by numerically evaluating
      the temperature distribution along the droplet interface. We propose a
      generalized relation for predicting the instantaneous volume of droplets with
      initial CA > 90 deg, irrespective of the mode of evaporation. 

PMID- 23952148
TI  - Anaerobic digestion for simultaneous sewage sludge treatment and CO
      biomethanation: process performance and microbial ecology.
AB  - Syngas is produced by thermal gasification of both nonrenewable and renewable
      sources including biomass and coal, and it consists mainly of CO, CO2, and H2. In
      this paper we aim to bioconvert CO in the syngas to CH4. A novel technology for
      simultaneous sewage sludge treatment and CO biomethanation in an anaerobic
      reactor was presented. Batch experiments showed that CO was inhibitory to
      methanogens, but not to bacteria, at CO partial pressure between 0.25 and 1 atm
      under thermophilic conditions. During anaerobic digestion of sewage sludge
      supplemented with CO added through a hollow fiber membrane (HFM) module in
      continuous thermophilic reactors, CO did not inhibit the process even at a
      pressure as high as 1.58 atm inside the HFM, due to the low dissolved CO
      concentration in the liquid. Complete consumption of CO was achieved with CO gas
      retention time of 0.2 d. Results from high-throughput sequencing analysis showed
      clear differences of the microbial community structures between the samples from
      liquid and biofilm on the HFM in the reactor with CO addition. Species close to
      Methanosarcina barkeri and Methanothermobacter thermautotrophicus were the two
      main archaeal species involved in CO biomethanation. However, the two species
      were distributed differently in the liquid phase and in the biofilm. Although the
      carboxidotrophic activities test showed that CO was converted by both archaea and
      bacteria, the bacterial species responsible for CO conversion are unknown. 

PMID- 23952151
TI  - From another perspective.
AB  - No abstract available for this article. 

PMID- 23952152
TI  - Resources of adaptation for daily living.
AB  - Occupational therapy addresses the chronically disabled person's adaptation to
      problems in daily living. Resources of adaptation are those inherent abilities
      and lifelong learnings which the individual uses to deal with daily living
      problems. Adaptation is described as flexible behavior to meet the changing needs
      of a changing environment. A review of the literature from a bio-social frame of
      reference identifies resources of adaptation. These resources are classified into
      a conceptual framework of three hierarchical levels corresponding to three time
      spans of adaptation: evolution, ontogenesis, and immediate learning. The
      classification of the resources of adaptation has implications for therapeutic
      evaluation and treatment, including the discovery and assessment of the resources
      of adaptation, a strategy for resource reorganization, and the environmental
      management of limited resources by the policy of "mini-max." 

PMID- 23952153
TI  - An Occupational Therapist's Perspective on Environmental Adaptations for the
      Disabled Elderly.
AB  - Services for the elderly and the handicapped despite their separate funding
      sources have much in common. A review of legislative mandates for each population
      as well as an overview of their common environmental needs and concerns is
      provided with special attention to housing. The relative merits of designing a
      barrier free environment versus adapting a residence to meet an individual's
      needs are explored and examples of both types of support are given. The role of
      the occupational therapist in the treatment of the disabled elderly is based on
      the premise that independence in daily living tasks promotes increased competence
      and can delay deterioration and institutionalization. Occupational therapists,
      because of their knowledge of functional independence as well sa their experience
      adapting environments, are invited to take on larger responsibilities bridging
      the gap between these two populations. 

PMID- 23952154
TI  - Liability considerations in the occupational therapy practice environment.
AB  - Occupational therapy as a complex service to patients requires of the therapist
      both creativity and the ability not only to accept the law and regulations but to
      exploit them for the freedoms they provide. This paper acknowledges this dual
      concern and offers some legal guidelines for dealing with it. It then explores
      the more important legal responsibilities of therapists in relation to the
      physical environment of patients. Included are facilities and equipment in the
      institution, in the community and in the home. Then it discusses practices and
      procedures which should be observed in providing legal health care. Some legal
      doctrines used by plaintiffs are described with recommendations for practices
      which should enable personnel to avoid most environment-related litigation. 

PMID- 23952155
TI  - Locating Rehabilitation Product Information Through ABLEDATA.
AB  - The ABLEDATA System, a program of the National Rehabilitation Information Center,
      is a computerized listing of commercially available aids and equipment for
      disabled persons. Anyone can obtain information from ABLEDATA by calling (202)635
      6090 or writing to 4407 Eighth St., NE, Washington, DC 20017. The following
      article outlines the development and organization of ABLEDATA and includes an
      expansion of the Information Broker Network. It describes the information
      available from ABLEDATA and illustrates a typical product search. It also
      discusses the use of the system by occupational therapists. Costs involved with
      using the system are discussed in the article. 

PMID- 23952156
TI  - Air transporation and the disabled.
AB  - Air transportation is becoming increasingly more accessible to the disabled
      traveller. This is due to many reasons. The disabled themselves are now very much
      a part of twentieth century society in which air travel plays a large role. To
      this end, several international organizations representing the disabled have been
      pressuring for increased accessibility. As well, the airlines have realized that
      the disabled represent a sizable market potential and thus they have begun
      accessibility and staff sensitization programs. This article will first provide a
      summary of the current situation for disabled travellers and will discuss such
      things as architectural barriers and other limitations both in the airport and on
      board the aircraft. The second section will discuss the current research into
      improving the comsort of the disabled passenger. Topics such as modification of
      on-board washroom facilities, adapted aids kits and on-board wheelchairs will be
      presented. Part three will be a short discussion of resources and organizations
      available to the disabled traveller. It is hoped that occupational therapists
      will gain a better understanding of the resources and developments in this area. 

PMID- 23952157
TI  - Adaptations for independent infant care by mothers who are disabled.
AB  - The objective of this paper is to present information that will increase
      functional independence in the everyday tasks of infant care for mothers with a
      disability. It focuses on one mother and her special problems in caring for her
      first child. Physical and psychosocial adaptations are addressed encompassing the
      major functions of the mother with a disability in an effort to establish the
      individual's unique ability to function successfully as a parent. Physical
      adaptations to make child caring accessible in both the home environment and away
      from home are explored. This covers activities requiring reaching, lifting,
      carrying as well as changing and feeding. Psychosocial adaptations influencing
      the person with a disability as parent focus on attitudes, recongition of
      strengths and limitations, and the feeling of belongingness in society. It is
      hoped that this paper will provide greater insight about independent infant care
      by mothers who are disabled and also stimulate new ideas for occupational
      therapists. 

PMID- 23952158
TI  - Adaptive equipment design and fabrication.
AB  - Occupational therapists can play a unique role in helping disabled persons
      procure adaptive equipment for those special problems of daily living. Treatment
      using only the devices listed in various catalogues does not always provide
      effective solutions. Sometimes only a particular item designed and fabricated
      specially to solve a functional problems brings the solution needed. Yet not all
      occupational therapists can or should engage in designing and making assistive
      equipment. This paper will explore the process of problem solving used by one
      occupational therapist/designer as he makes adaptive equipment. Seven distinct
      parts of the process will be discussed as a guide for other occupational
      therapists who may wish to increase their skill in this area of professional
      activity. 

PMID- 23952159
TI  - Prostheses, equipment, adapted performance.
AB  - As a member of the rehabilitation team with direct responsibility for a treatment
      program for the person with amputation(s), the occupational therapist has marked
      influence on the patient's adjustment to his disability. In addition, the
      occupational therapist can influence a patient's choices regarding use of
      adaptations or substitutions achieved by prostheses, equipment or body motion
      alone. The author, working in a comprehensive rehabilitation center, The Kessler
      Institute for Rehabilitation, where many amputees of all stages are treated, will
      outline basic principles in treatment planning for the person with amputation(s).
      In addition, treatment choices will be examined with the discussion focusing on
      different levels of amputations, and differing physical and psychological needs
      of the adult and child. Suggestions are offered for approaches to using
      protheses, equipment, or adapted performance in training persons with
      amputations. The author also explores why rejection of an upper limb prosthesis
      or equipment might not signify treatment failure. Therapists have responsibility
      for introducing all options for daily function to the patient and family as part
      of the occupational therapy treatment program, but must remember that final
      decisions are made by patients. 

PMID- 23952160
TI  - Occupational therapy and rehabilitation engineering.
AB  - Occupational therapists in clinical settings are often challenged with difficult
      problems in the selection, application and modification of complex mechanical,
      electrical or structural aids for persons with severe disability who wish to
      improve their levels of independence. At the Rehabilitation Institute of Chicago,
      solutions to such situations are facilitated by interaction between the
      occupational therapist and the rehabilitation engineer. In this paper, following
      the identification of the population served and their specialized needs, the
      working relationship between the occupational therapist and rehabilitation
      engineer will be discussed through presentation of two case studies. Various
      commercially available equipment will be considered along with modifications
      possible, and finally, customer design solutions will be given for some problems.
      Given the growing store of resources for assisting clients who have special
      needs, many creative systems can be developed in therapists and engineers combine
      their respective knowledge and skills in problem solving. 

PMID- 23952161
TI  - Project threshold.
AB  - Project Threshold is a program which uses an interdisciplinary approach to assist
      persons with physical disabilities in solving their functional problems at home
      or at work. The program originated to provide rehabilitation engineering services
      to those persons in the community whose needs were not being met through more
      traditional services. As the program evolved, it was evident that an
      interdisciplinary team was needed to fully develop the potential of this service
      delivery program. Occupational therapists were identified as important members of
      this team because of their expertise in functional assessment, analysis of
      activity and teaching such activities. Pivotal to the project's success is the
      adherence to a thorough and sequential service delivery process. This process is
      illustrated by the presentation of two cases; one involving an independent living
      evaluation, and the other a worksite assessment. 

PMID- 23952162
TI  - Occupational therapy and rehabilitation engineering.
AB  - As new and more sophisticated technology is represented in equipment and devices,
      occupational therapists are challenged to expand their roles as evaluators for
      and providers of these more complex assistive devices. Being experts in
      understanding disability and how to maximize function for daily activities will
      enable occupational therapists to be key team members in the growing specialty of
      providing technical aids. "Technical persons" ranging from rehabilitation
      engineers to carpenters, working in conjection with occupational therapists, can
      form a unique partnership in which the skills of each combine to solve a variety
      of daily living problems. This paper will discuss the relationship of one
      Rehabilitation Engineering Program operating as a self supporting, fee-for
      service program within the Orthopaedic Department of a Medical School. A case
      study will illustrate problem solving strategies utilized in the delivery of
      technical services. 

PMID- 23952163
TI  - Computer environmental control units for the severely physically disabled.
AB  - Environmental Control Units (ECU) range from inexpensive three-function devices
      to sophisticated computer systems which also have communication, recaretion, and
      other capabilities as well. Four commercially available systems are described in
      terms of hardware and software requirements, method of access, method of
      environmental control, and descriptions of additional capabilities. Attention is
      given to other products that may be required for accessing the computer,
      including keyguards, special keyboards, and various switches. Criteria for
      choosing appropriate candidates and systems is discussed as well as implications
      for the occupational therapist. 

PMID- 23952164
TI  - Rx.

PMID- 23952165
TI  - Something new and useful.
AB  - No abstract available for this article. 

PMID- 23952168
TI  - Psychosomatics in obstetrics and gynecology - evaluation of a compulsory
      standardized teaching program.
AB  - OBJECTIVE: This observational study was aimed at assessing the effect of case
      supervision in small groups over a two-year period as part of a standardized
      psychosomatic basic training for future obstetrician-gynecologists from the
      physicians' perspective. METHODS: The supervised groups were evaluated by
      questionnaires distributed to all 128 candidates at the beginning (T1), at half
      time (T2) and at the end of the course (T3). Aside from a validated battery of
      questions on self-efficacy, items included self-estimated psychosomatic
      competence, professional satisfaction as well as a validation of the training
      program. RESULTS: The training program was associated with a significant increase
      of self-reported psychosomatic competence (55.0/68.9, p = 0.000) and self
      efficacy (2.4/2.8, p = 0.0011). While major changes occurred at the end of the
      first year of the supervised groups, no further enhancement could be demonstrated
      throughout the second year. A total of 44 (88%) study participants who answered
      at T3 considered the training program as helpful. CONCLUSIONS: The presented
      teaching program - more precisely the supervised groups - seemed to be effective
      in increasing self-estimated psychosomatic competence and self-efficacy in future
      specialists for obstetrics and gynecology. It may serve as a model for the
      systematic integration of standardized psychosomatic basic training into the
      education of obstetrician-gynecologists.

PMID- 23952169
TI  - Self-efficacy beliefs and fear of childbirth in nulliparous women.
AB  - OBJECTIVE: To explore how childbirth self-efficacy, i.e. outcome expectancy and
      efficacy expectancy, was associated with fear of childbirth (FOC) and how
      efficacy expectancy and FOC, respectively were related to socio-demographic
      characteristics, mental problems and preference for a caesarean section. METHODS:
      In this cross-sectional study, a consecutive sample of 1000 pregnant nulliparous
      women was sent the Wijma Delivery Expectancy Questionnaire and Childbirth Self
      Efficacy Inventory. Statistical analyses were performed on data from 423 women.
      RESULTS: Outcome expectancy and efficacy expectancy correlated significantly and
      positively, FOC correlated significantly and negatively with both outcome
      expectancy and efficacy expectancy. Women with severe FOC (20.8%) had a
      significantly lower level of education (p = 0.001), and had more often sought
      help because of mental problems (p = 0.004). They were more likely to have low
      efficacy expectancy (p < 0.001) and to prefer a caesarean section instead of a
      vaginal birth (p < 0.001). CONCLUSIONS: Lower efficacy expectancy was associated
      with higher FOC while preference for a caesarean section was not. Improvement of
      self-efficacy could be a part of care for women with FOC during pregnancy;
      however, it would not be enough for fearful women who wish to have a caesarean
      section.

PMID- 23952170
TI  - Recovery after unsuccessful in vitro fertilization: the complex role of
      resilience and marital relationships.
AB  - The failure rate of in vitro fertilization (IVF) is around 75% per cycle. These
      unsuccessful attempts can provoke acute clinical depression and other problems.
      Although practitioners often recommend cognitive reappraisal, rather than
      avoidance, to cope with these difficulties, previous research has not established
      the psychosocial determinants of adaptive coping strategies. Arguably, resilience
      could encourage cognitive reappraisal, because resilient individuals feel
      confident they can overcome their emotions, whereas marital quality could prevent
      avoidance, because individuals feel secure enough to reflect upon their distress.
      Consequently, resilience and marital quality could facilitate recovery over time.
      To explore these possibilities, 184 women, all of whom had unsuccessfully
      completed IVF treatment, completed a questionnaire that gauged their levels of
      self-reported depression since their last IVF attempt as well as resilience and
      marital quality. Immediately after the unsuccessful attempt, resilience was
      inversely, whereas marital quality was positively, related to depression.
      However, within this cross-sectional sample after greater time had elapsed,
      marital quality became increasingly beneficial and was negatively associated with
      depression. These findings imply that resilience can curb the initial distress;
      in contrast, marital quality may enable individuals to reflect upon their trauma,
      initially amplifying distress but eventually facilitating recovery. Future
      research would benefit from longitudinal studies, illustrating whether resilience
      and marital quality at one time predict changes in distress at subsequent times.

PMID- 23952171
TI  - Anticonvulsant pharmacotherapy for generalized and localized vulvodynia: a
      critical review of the literature.
AB  - Anticonvulsant therapy has occasionally been recommended to treat vulvodynia.
      However, convincing evidence to support this therapeutic option is lacking. The
      goal of this study was to critically review studies published on the
      effectiveness of anticonvulsants for the treatment of vulvodynia. Evaluation of
      the methodological quality of relevant publications was the main outcome measure.
      MEDLINE, PubMED and Cochrane were used to identify studies published in English
      between January 1999 and February 2013. Searches were performed between December
      2012 and February 2013. Articles were appraised with the Oxford Centre for
      Evidence-Based Medicine - Levels of Evidence. Eight relevant studies were
      identified: two case reports, three retrospective studies, two non-randomized
      prospective studies and one open-label pilot trial study. Gabapentin formed the
      main focus (87.5%) to reduce vulvar pain; success rates ranged from 50 to 82%.
      Lamotrigine was used in one study (12.5%) to relieve symptoms; satisfaction was
      reported in 82%. These results seem promising, but the majority of studies have
      several methodological weaknesses regarding sample size and design. Insufficient
      evidence was available to recommend anticonvulsants for the treatment of
      vulvodynia. Further studies are necessary with double-blind, randomized
      controlled designs to investigate the effectiveness of anticonvulsant therapy for
      vulvodynia.

PMID- 23952172
TI  - Labour pain: from the physical brain to the conscious mind.
AB  - The study of pain goes well beyond the study of anatomy and physiology. To fully
      understand a phenomenon such as pain, one must consider the realm in which it
      exists - the conscious mind. This paper aims to explore the concept of the
      conscious mind and its relevance to the human experience of labour pain.
      Understanding the interactions between the mind, brain, body, social environment
      and natural world on the experience of pain enables a more comprehensive
      conception of labour pain. Reaffirming that pain is an embodied subjective
      experience is important during this current era in pain science research that
      seems to lean towards neuroreductionism and conceptualises pain as a pathological
      by-product of disease. Labour pain, however, is a clear demonstration that pain
      is not always a signal of bodily disorder. The experience of pain is generated by
      the brain and is realised through the conscious mind. Thus, the study of pain -
      particularly complex pains such as labour pain - should focus not just on the
      physical body and neural processes in the brain but must aim to include, and be
      capable of capturing, all elements that constitute it; the mind, brain, body and
      the environment.

PMID- 23952173
TI  - Multiple paternity and sperm competition in the sibling species Drosophila
      buzzatii and Drosophila koepferae.
AB  - Sperm competition (SC) is a major component of sexual selection that enhances
      intra- and intersexual conflicts and may trigger rapid adaptive evolution of
      sexual characters. The actual role of SC on rapid evolution, however, is poorly
      understood. Besides, the relative contribution of distinctive features of the
      mating system to among species variation in the strength of SC remains unclear.
      Here, we assessed the strength of SC and mating system factors that may account
      for it in the closely related species Drosophila buzzatii and Drosophila
      koepferae. Our analyses reveal higher incidence of multiple paternity and SC risk
      in D. buzzatii wild-inseminated females. The estimated number of fathers per
      brood was 3.57 in D. buzzatii and 1.95 in D. koepferae. In turn, the expected
      proportion of females inseminated by more than one male was 0.89 in D. buzzatii
      and 0.58 in D. koepferae. Laboratory experiments show that this pattern may be
      accounted for by the faster rate of stored sperm usage observed in D. koepferae
      and by the greater female remating rate exhibited by D. buzzatii. We also found
      that the male reproductive cost of SC is also higher in D. buzzatii. After a
      female mated with a second male, first-mating male fertility was reduced by 71.4%
      in D. buzzatii and only 33.3% in D. koepferae. Therefore, we may conclude that
      postmating sexual selection via SC is a stronger evolutionary force in D.
      buzzatii than in its sibling. 

PMID- 23952174
TI  - Surface-enhanced Raman spectroscopy for real-time monitoring of reactive oxygen
      species-induced DNA damage and its prevention by platinum nanoparticles.
AB  - We have successfully demonstrated the potential of surface-enhanced Raman
      spectroscopy (SERS) in monitoring the real time damage to genomic DNA. To reveal
      the capabilities of this technique, we exposed DNA to reactive oxygen species
      (ROS), an agent that has been implicated in causing DNA double-strand breaks, and
      the various stages of free radical-induced DNA damage have been monitored by
      using SERS. Besides this, we showed that prompt DNA aggregation followed by DNA
      double-strand scission and residual damage to the DNA bases caused by the ROS
      could be substantially reduced by the protective effect of Pt nanocages and
      nearly cubical Pt nanopartcles. The antioxidant activity of Pt nanoparticles was
      further confirmed by the cell viability studies. On the basis of SERS results, we
      identified various stages involved in the mechanism of action of ROS toward DNA
      damage, which involves the DNA double-strand scission and its aggregation
      followed by the oxidation of DNA bases. We found that Pt nanoparticles inhibit
      the DNA double-strand scission to a significant extent by the degradation of ROS.
      Our method illustrates the capability of SERS technique in giving vital
      information about the DNA degradation reactions at molecular level, which may
      provide insight into the effectiveness and mechanism of action of many drugs in
      cancer therapy. 

PMID- 23952175
TI  - Chemical synthesis of U1 snRNA derivatives.
AB  - U1 snRNA is an interesting biological tool for splicing correction and regulation
      of gene expression. However, U1 snRNA has never been chemically synthesized. In
      this study, the first chemical synthesis of U1snRNA and its analogues was carried
      out. Moreover, it was found that the binding affinity of the modified U1 snRNA
      with an ethylene glycol linkage to snurportin 1 (nuclear import adaptor) was as
      high as that of the unmodified RNA. 

PMID- 23952177
TI  - Laxity of the vaginal introitus after childbirth: nonsurgical outpatient
      procedure for vaginal tissue restoration and improved sexual satisfaction using
      low-energy radiofrequency thermal therapy.
AB  - INTRODUCTION: Vaginal childbirth may result in vaginal introital laxity, altered
      genital sensation during sexual intercourse, and reduced sexual satisfaction. We
      report the long-term effectiveness of a single nonsurgical procedure with
      radiofrequency (RF) energy for laxity at the vaginal introitus. MATERIALS AND
      METHODS: Prospective single-arm study of 30 premenopausal women (21-52 year) with
      one 30-minute office procedure using RF applied to the vaginal introitus; 12
      month outcome assessments included the linguistic validated Japanese versions of
      the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised
      (FSDS-R) and the Vaginal Laxity and Sexual Satisfaction Questionnaires. RESULTS:
      Sexual function improved significantly throughout 6 months (30 subjects); mean
      FSFI total score was 22.4+/-6.7 before treatment and then improved to mean 26.0+/
      5.8 at month 6 (P=0.002), inclusive of improved scores in five of six FSFI
      domains except desire (P<0.001 -<0.01). In the 22 of 30 subjects remaining
      evaluable at 12 months, the mean was 26.0+/-5.2 (P=0.08). Distress related to
      sexual activity decreased significantly; baseline FSDS-R mean score of 15.8+/
      11.7 improved to 9.8+/-8.0 at one month and was sustained throughout 12 months
      (P<0.001 - 0.002). Subjects reported decreased vaginal laxity within the first
      month after the procedure (P<0.001); responses peaked, and effectiveness was
      sustained through 12 months (P<0.001). CONCLUSIONS: A single nonsurgical office
      based RF procedure for vaginal introital laxity achieved significant and
      sustainable 12-month effectiveness with respect to improved integrity at the
      vaginal introitus and improved sexual satisfaction. Treatment was well-tolerated
      with no adverse events.

PMID- 23952178
TI  - Healthcare utilization of subgroups of Latinas: shortfalls in data
      interpretation.

PMID- 23952179
TI  - Liver transplantation in alcoholic patients--reply.

PMID- 23952180
TI  - Asymptomatic peripheral retinal hemorrhages as a manifestation of interferon beta
      1a retinopathy.
AB  - We present a case of retinopathy found incidentally in an asymptomatic patient
      receiving treatment with interferon beta 1a for multiple sclerosis. She was found
      to have peripheral dot and blot hemorrhages with no cotton wool spots. It is
      possible that interferon beta 1a retinopathy is more common than previously
      reported, as it may be asymptomatic with patients having peripheral retinal
      hemorrhages.

PMID- 23952181
TI  - The effect of mydriatic solutions on cognitive function.
AB  - INTRODUCTION: Anticholinergic and sympathomimetic ophthalmic solutions are used
      for mydriasis. These solutions have well-documented systemic side effects despite
      their topical administration. However, no studies have been conducted regarding
      the effect of mydriatic drops on cognitive function. The purpose of this study is
      to determine the effect, if any, of mydriatic drops on cognitive function,
      including memory, concentration, and orientation. METHODS: Participants were
      randomized into two groups using the technique of permuted block randomization,
      and randomization was stratified by gender, age, and education. Participants in
      Group 1 completed the Montreal Cognitive Assessment (MoCA) test with undilated
      pupils, while participants in Group 2 completed the MoCA test with dilated
      pupils. Administration time of the MoCA test was approximately 10 minutes, and
      each participant could receive a maximum of 30 points, with a score of 26 or
      greater being considered normal cognitive function. Dilation was achieved in both
      eyes with a combination of tropicamide 0.5% and phenylephrine 2.5%. RESULTS:
      There was no statistical difference between the MoCA scores of Group 1 and Group
      2 (p = 0.65). In addition, MoCA scores were not statistically different between
      the glaucoma and non-glaucoma subpopulations within each group. MoCA test scores
      were shown to correlate with education (p = 0.004), age (p = 0.0003), and race (p
      = 0.03). Patients with confirmed or suspected glaucoma whom eyes dilated required
      10.8 minutes to complete the MoCA test, while patients with no confirmed or
      suspected glaucoma whom eyes dilated required 8.5 minutes to complete the test (p
      = 0.02). DISCUSSION: Age, race, and education were found to be the most important
      factors affecting cognitive function in this study. There was no significant
      difference in the MoCA test scores of participants with confirmed or suspected
      glaucoma and participants without glaucoma. There was also no significant
      difference in the MoCA scores of dilated participants and non-dilated
      participants as a whole. However, dilation significantly increased the amount of
      time required to complete the MoCA test among the glaucoma and suspected-glaucoma
      population. The results of this study suggest that physicians should spend more
      time with dilated glaucoma patients while explaining medical conditions and
      treatment instructions in order to ensure that patients have adequate time to
      comprehend instructions for glaucoma management.

PMID- 23952182
TI  - From the editor-in-chief's desk.

PMID- 23952183
TI  - Feasibility of conducting a randomized controlled trial of telemental health with
      children diagnosed with attention-deficit/hyperactivity disorder in underserved
      communities.
AB  - OBJECTIVE: Telemental health (TMH), the use of videoteleconferencing to provide
      care that is usually delivered in person, is increasingly used to rectify
      disparities in access to care. Few studies, however, have been conducted to
      demonstrate the effectiveness of TMH as a service delivery model. The Children's
      Attention-Deficit/Hyperactivity Disorder (ADHD) Telemental Health Treatment Study
      (CATTS) is a randomized clinical trial (RCT) of TMH conducted in multiple
      underserved communities. This article reports on the feasibility of conducting an
      effectiveness trial of TMH with children. METHODS: The CATTS trial used
      videoteleconferencing to provide guideline-based care and secure web sites to
      coordinate key aspects of trial implementation, such as participant recruitment
      and retention, intervention fidelity, and completion of assessments. RESULTS: The
      CATTS trial engaged seven communities and 150 primary care providers as partners
      in the study, and enrolled 223 children 5.5-12.9 years old. The intervention
      group completed an average of 5.3 of 6.0 planned sessions and 96% of controls
      completed a TMH consultation. Both groups completed an average of 4.8 of the 5.0
      assessments. Clinicians demonstrated high fidelity to their treatment protocols.
      Minor technical difficulties did not interfere with providing care. CONCLUSIONS:
      The CATTS trial demonstrated the feasibility of conducting an RCT of TMH with
      children living in multiple underserved communities. Telecommunications
      technologies can facilitate the coordination of research activities across sites
      and clinicians. Future trials should work closely with study partners to ensure
      referral of a representative study sample. Further trials are needed to help
      establish the effectiveness of TMH as a service delivery model. TRIAL
      REGISTRATION: http://clinicaltrials.gov/show/NCT00830700 .

PMID- 23952184
TI  - Caregivers' distress: youth with attention-deficit/hyperactivity disorder and
      comorbid disorders assessed via telemental health.
AB  - OBJECTIVE: This article evaluates the additive effects of children's comorbid
      conditions with attention-deficit/hyperactivity disorder (ADHD) in relation to
      caregivers' distress, in a clinical trial conducted through telemental health
      (TMH). METHODS: The Children's ADHD Telemental Health Treatment Study (CATTS) is
      examining the effectiveness of treatment delivered via TMH for children with ADHD
      who are living in underserved communities. The CATTS trial recruited 223 children
      (MU=9.53+/-2.06 years) and their caregivers. Diagnoses of ADHD and comorbid
      oppositional defiant disorder (ODD) and anxiety disorders (ADs) were established
      with the Child Behavior Checklist and the Computerized Diagnostic Interview
      Schedule for Children. We took advantage of rich baseline data from the CATTS
      trial to investigate associations between caregivers' distress and children's
      comorbid mental health conditions. Caregivers' distress was assessed with the
      Patient Health Questionnaire-9, Parenting Stress Index, and Caregiver Strain
      Questionnaire. ANOVAs were used to compare children with ADHD alone with children
      having one comorbid condition (ODD or ADs) and children having two comorbid
      conditions (ODD and ADs). RESULTS: Three quarters (75.3%) of participants met
      criteria for ODD and/or AD comorbid with ADHD: 24.7% had neither comorbidity;
      47.5% had ODD or AD; and 27.8% had both ODD and AD comorbidities. The parents of
      children with multiple comorbid conditions experienced the highest levels of
      depression, stress, and burden of care. CONCLUSIONS: The CATTS sample that was
      recruited from underserved communities provided evidence of additive effects of
      child psychiatric comorbidities with caregivers' distress, echoing earlier
      findings from the Multi-modal Treatment of ADHD (MTA) study that was conducted
      with a metropolitan sample of youth. Results indicate that caregivers' distress
      should be addressed in developing treatment models for children with ADHD.
      CLINICAL TRIALS REGISTRY: http://clinicaltrials.gov/show/NCT00830700 .

PMID- 23952185
TI  - Treatment outcomes with lisdexamfetamine dimesylate in children who have
      attention-deficit/hyperactivity disorder with emotional control impairments.
AB  - OBJECTIVE: The purpose of this study was to assess lisdexamfetamine dimesylate
      (LDX) treatment effects based on baseline emotional control dysfunction in
      children with attention-deficit/hyperactivity disorder (ADHD) categorized with or
      without impairments of executive function (EF) emotional control. METHODS: Post
      hoc analyses of a 7 week, open-label LDX study in children with ADHD (American
      Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders,
      4th ed., Text Revision [DSM-IV-TR] defined) and impairments in EF control of
      emotional response. At baseline, participants were dichotomized by Behavior
      Rating Inventory of EF (BRIEF) emotional control domain T-scores of >=65 (with
      impairment) or <65 (without impairment). ADHD Rating Scale-IV (ADHD-RS-IV), BRIEF
      Global Executive Composite and emotional control domain, Expression and Emotion
      Scale for Children (EESC) scores, Pearson correlations for BRIEF versus ADHD-RS
      IV and EESC, and Clinical Global Impressions scores were assessed at baseline and
      end of study (week 7)/early termination (EOS/ET) by baseline category of BRIEF
      emotional control impairment. Safety assessments included treatment-emergent
      adverse events (TEAEs). RESULTS: At baseline and EOS/ET, respectively, 53.0% and
      20.7% met criteria for emotional control impairment. Participants with and
      without emotional control impairments had similar ADHD-RS-IV change scores. Mean
      (SD) change from baseline for those with and without emotional control
      impairments were -20.8 (12.89) and -14.6 (11.25) for BRIEF global scores and 
      16.0 (13.19) and -5.0 (9.48) for BRIEF emotional control domain scores.
      Participants with emotional control impairments had greater mean EESC total score
      changes. BRIEF emotional control domain and all ADHD-RS-IV scores indicated
      moderate correlations between change scores (all p<0.0001). Overall, 84.9% of
      participants had TEAEs (mostly mild-to-moderate in severity); 3.8% discontinued
      because of TEAEs. CONCLUSIONS: The proportion of children with behavioral
      impairments in EF control of emotional response decreased during LDX treatment.
      ADHD symptoms improved in both groups. The moderate correlations between EF
      behaviors and ADHD symptoms suggest there may be utility in evaluating behavioral
      domains beyond core ADHD symptoms.

PMID- 23952186
TI  - Are non-serious adverse reactions to psychiatric drugs really non-serious?
AB  - OBJECTIVE: The EudraVigilance Pharmacovigilance system classifies the seriousness
      of adverse drug reactions (ADRs) based on the requirement of hospital care. To
      date, no systematic study has been conducted on the impact of non-serious ADRs,
      in terms of therapy continuation and course of the underlying disease. We
      analyzed a pediatric population receiving psychiatric care and subjected to drug
      treatment, to assess whether non-serious ADRs do or do not have a relevant
      clinical impact. METHODS: Data from a 1 year period were collected, which
      included: Administered drugs, choices made to manage the ADRs, the long-term (6
      month) effect of these interventions on the course of the reaction, and their
      impact on the drug treatment for the underlying pathology. RESULTS: Observed ADRs
      were concordant with those previously described for the same drug classes, and
      mainly comprised alterations of behavior, mood, and sleep (53%) and excessive
      variations of appetite and body weight (39%). The type of drug influenced the
      management decision, as we found that drug discontinuation was the most frequent
      strategy employed to resolve ADRs, especially with drugs employed in the
      treatment of attention-deficit/hyperactivity disorders (63%, p<0.05), whereas
      management of antipsychotics mainly relied upon drug substitution (21%, p<0.01).
      Also, the type of ADR influenced the management decision, as alterations of
      behavior, mood, and sleep were seldom managed by maintaining the drug unchanged
      (10%, p<0.05), at variance with appetite/weight alteration ADRs (unchanged in
      41%, p<0.01). Follow-up information revealed that drug discontinuation was most
      efficient at treating ADRs (no persistent ADRs, p<0.01), but had a severe impact
      on the course of the underlying psychiatric disease. Conversely, management of
      ADRs by maintaining the original drug even if at different dosage did not lead to
      an amelioration of the reactions; however, as it caused a significant clinical
      improvement (83%, p<0.04) that superseded the ADR in terms of clinical benefit.
      CONCLUSIONS: These data suggest that the best strategy to improve both ADR
      management and the clinical course of patients is to limit, whenever possible,
      changes to the original therapy. Optimization of the actual therapeutic regimes
      also might benefit from development of specific pharmacokinetic and
      pharmacodynamic monitoring programs.

PMID- 23952187
TI  - The impact of long-acting medications on attention-deficit/hyperactivity disorder
      treatment disparities.
AB  - OBJECTIVE: Long-acting stimulants have increased medication adherence for many
      children diagnosed with attention deficit/hyperactivity disorder (ADHD), but it
      is unknown whether the increase has been similar across racial/ethnic groups. Our
      objective was to determine whether differences in medication utilization and
      adherence among white, black, and Hispanic ADHD-diagnosed children and
      adolescents narrowed following the introduction of long-acting stimulants in the
      1990s. METHODS: We conducted a retrospective analysis of Florida Medicaid claims
      data from fiscal years 1996-2005. At each of three cross sections, we identified
      children and adolescents 3-17 years of age with at least two claims with an ADHD
      diagnosis. We used linear regression to model disparities over the study period
      in utilization of any ADHD medications (utilization of long-acting medication
      specifically) and medication adherence, and identified patient level, treatment
      setting, and geographic contributors to disparities. RESULTS: Although ADHD
      medication utilization was lower for ADHD-diagnosed minorities than whites in all
      years, minorities were as likely as whites to switch to long-acting medications.
      The increase in prescribed days following long-acting medication diffusion was
      comparable for white and black medication users (40 and 43 days, respectively),
      but lower for Hispanics (27 days). Geography and provider setting helped to
      explain disparities in medication utilization overall, but disparities in
      adherence were not explained by any of the covariates. CONCLUSIONS: Despite
      equivalent switching to long-acting medications in the study period, minorities
      continued to utilize all ADHD medications less than did whites, and for shorter
      periods. Provider setting helps explain the ADHD medication utilization gap. High
      volume, minority-serving providers are potential targets for future interventions
      related to improved communication about medication and follow-up after medication
      initiation.

PMID- 23952188
TI  - Baseline severity of parent-perceived inattentiveness is predictive of the
      difference between subjective and objective methylphenidate responses in children
      with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: The purpose of this study was to find potential variables associated
      with the difference between subjective and object treatment responses in children
      with attention-deficit/hyperactivity disorder (ADHD) treated with OROS
      methylphenidate (MPH). METHODS: We conducted a post-hoc analysis of data from a
      multicenter, open-label, 12 week trial of OROS-MPH in Korean children with ADHD.
      The subjective outcome measurement was the parent version of the ADHD Rating
      Scale-IV (ARS-P), and the objective outcome measurement was the Continuous
      Performance Test (CPT). We compared the children's demographic and disease
      related variables among four groups, classified according to whether they showed
      subjective or objective improvement after MPH treatment. RESULTS: Higher baseline
      inattentive scores on the ARS-P were associated with a significantly higher
      probability of subjective treatment response among objective nonresponders
      (p=0.033). Lower baseline inattentive scores on the ARS-P were associated with a
      significantly higher probability of subjective nonresponse among objective
      responders (p=0.045). Lower baseline omission errors (p=0.006) and response time
      variability scores (p=0.011) on the CPT were associated with a significantly
      higher probability of both objective and subjective responses, compared with both
      types of nonresponse to treatment. CONCLUSIONS: The baseline severity of parent
      perceived inattentive symptoms was predictive of differences in subjective and
      objective treatment responses, and the baseline severity of neuropsychological
      deficit (inattention and inconsistency of attention) was predictive of responses,
      using both subjective and objective measurements.

PMID- 23952189
TI  - Combination use of atomoxetine hydrochloride and olanzapine in the treatment of
      attention-deficit/hyperactivity disorder with comorbid disruptive behavior
      disorder in children and adolescents 10-18 years of age.
AB  - OBJECTIVE: The aim of this study was to assess the use of atomoxetine and
      olanzapine in combination to treat attention-deficit/hyperactivity disorder
      (ADHD) and comorbid disruptive behaviors in children and adolescents 10-18 years
      of age. METHODS: Eleven subjects ages 10-18 received open-label atomoxetine and
      olanzapine for a 10 week treatment period. Patients were assessed at baseline, 2
      weeks, 4 weeks, 6 weeks, and 10 weeks (posttreatment). ADHD improvement was
      measured through the ADHD Rating Scale (ADHD-RS) (Investigator and Parent
      ratings). Aggression was measured through the Modified Overt Aggression Scale
      (MOAS). RESULTS: The combined use of atomoxetine and olanzapine resulted in
      statistically significant improvement in ADHD symptoms and overt aggression from
      baseline to posttreatment. As evidenced by a 33% reduction in symptoms on the
      ADHD-RS-I and the MOAS, 73% of patients were considered responders to ADHD
      treatment, whereas 55% responded to treatment for aggression. Both medications
      were generally well tolerated. Olanzapine treatment was associated with
      significant weight gain. Patients gained, on average, 3.9 kg. throughout the
      treatment period. CONCLUSIONS: These data provide initial evidence that
      combination use of atomoxetine and olanzapine for the treatment of ADHD and
      comorbid disruptive behaviors was effective in reducing ADHD symptoms and
      aggressive behavior in a 10 week treatment period.

PMID- 23952190
TI  - Obsessive-compulsive disorder and comorbid attention-deficit/hyperactivity
      disorder: a complex diagnostic disentanglement and treatment.

PMID- 23952191
TI  - Dopamine receptors and the pharmacogenetics of side-effects of stimulant
      treatment for attention-deficit/hyperactivity disorder.

PMID- 23952192
TI  - A case of severe akathisia with atomoxetine.

PMID- 23952193
TI  - Dose-dependent Raynaud's phenomenon developing from use of atomoxetine in a girl.

PMID- 23952194
TI  - Bevacizumab for the treatment of glioblastoma.
AB  - Glioblastoma (GB) is the most common adult malignant primary brain tumor that
      arises from glial precursor cells. Survival in GB is variable ranging from 6 to
      20 months notwithstanding current standard of care (SOC) treatment. Therapy has
      improved, but nonetheless GB is still invariably recurrent and incurable.
      Treatment options at recurrence include re-operation with or without carmustine
      (BCNU) wafer implantation (Gliadel), re-irradiation and standard/experimental
      chemo- or targeted therapy. Recurrent GB radiographic response rates to cytotoxic
      chemotherapy are less than 10% and median 6-month progression-free survival
      (PFS6) is 15%. With the recognition of the importance of tumor angiogenesis and
      the development of targeted therapy based on angiogenic inhibition, two pivotal
      trials of the VEGF-directed monoclonal antibody, bevacizumab (BEV, Avastin), were
      conducted in recurrent GB. Based upon the results of these two prospective US
      trials (median radiographic response rate: 25%; PFS6: 40%), BEV as a single agent
      was granted accelerated approval in the USA for recurrent GB. This review is a
      summary of current literature and clinical trials research in the role of BEV for
      the treatment of newly diagnosed and recurrent GB and potential future use of
      anti-angiogenic therapies in the management of GB.

PMID- 23952195
TI  - Meta-analysis: pharmacological treatment of pathological gambling.
AB  - BACKGROUND: This meta-analysis investigates the efficacy of pharmacological
      treatments for pathological gambling (PG). METHODS: We searched for randomized,
      placebo-controlled trials examining pharmacotherapy of pathological gamblers. A
      fixed-effects model was used to calculate the standardized mean difference (SMD)
      of the benefit of medication (stratified by class) compared to placebo. Secondary
      analyses examined the effects of publication bias, year of publication and
      adherence to intention-to-treat (ITT) principles on reported efficacy of
      interventions. RESULTS: Meta-analysis included 14 trials involving 1024
      participants. Opiate antagonists demonstrated a small but significant benefit
      compared to placebo (SMD = 0.22 +/- 0.10 (95% CI: 0.03-0.41), z = 2.3, p = 0.02).
      The reported efficacy of opiate antagonists was significantly associated with non
      adherence to ITT principles in trials and earlier year of publication. Other
      medications had non-significant effect sizes compared to placebo but similar in
      magnitude to opiate antagonists. CONCLUSIONS: Current trial data provides limited
      support for the use of any pharmacological agent in the treatment of pathological
      gambling.

PMID- 23952196
TI  - Leg stiffness during phases of countermovement and take-off in vertical jump.
AB  - With respect to cyclic movements such as human gait, running or hopping, leg
      stiffness is a little variable parameter. The aim of this study was to
      investigate changes in leg stiffness during the phase of countermovement and take
      off when performing a single maximum counter-movement jump. Kistler force plates
      and a BTS SMART system for comprehensive motion analysis were employed in the
      study. The study covered a group of 12 athletes from university basketball teams.
      Leg stiffness was calculated in those parts of countermovement and take-off
      phases where its level is relatively constant and the relationship F(Deltal) is
      similar to linear one. Mean total stiffness (+/-SD) in both legs in the
      countermovement phase amounted to 6.5 +/- 1.5 kN/m, whereas during the take-off
      phase this value was 6.9 +/- 1 kN/m. No statistically significant differences
      were found between leg stiffness during the countermovement phase and takeoff
      phase in the study group at the level of significance set at alpha = 0.05. This
      suggests that the leg stiffness in phase of countermovement and phase of take-off
      are much similar to each other, despite different function of both phases.
      Similar to cyclic movements, leg stiffness turned out relatively constant when
      performing a single vertical jump. There are also reported statistically
      significant correlations between body mass, body height, length of lower limbs
      and leg stiffness. The stiffness analysed by the authors should be understood as
      quasi-stiffness because the measurements of DeltaF(Deltal) were made during
      transient states where inertia and dumping forces are likely to affect the final
      result. 

PMID- 23952197
TI  - Borderline personality and bipolar disorder: the limits of phenomenology.

PMID- 23952198
TI  - Factors associated with feeding difficulties in the very preterm infant.
AB  - AIM: To investigate early medical and family factors associated with later
      feeding risk in preterm infants. METHODS: For this longitudinal study, 136
      infants born <=30 weeks gestation were enrolled. Medical and social background
      factors were assessed at term equivalent age. Infants underwent magnetic
      resonance imaging, neurobehavioral evaluation and feeding assessment. Parent
      involvement in the neonatal intensive care unit was tracked, and maternal mental
      health was assessed at neonatal intensive care unit discharge. At age 2 years,
      feeding outcome was assessed using the Eating Subscale of the Infant-Toddler
      Social Emotional Assessment (n = 80). Associations between feeding problems at
      age 2 years and (i) early medical factors, (ii) neurobehavioral functioning and
      feeding at term equivalent age, (iii) cerebral structure and (iv) maternal mental
      health were investigated using regression. RESULTS: Eighteen (23%) children had
      feeding problems at age 2 years. Feeding problems were associated with early
      hypotonia (p = 0.03; beta = 0.29) and lower socio-economic status (p = 0.046;
      beta = -0.22). No associations were observed between early medical factors, early
      feeding performance, cerebral structure alterations or maternal well-being and
      feeding outcome. CONCLUSION: Early hypotonia may disrupt the development of oral
      motor skills. Hypotonia and poor feeding also may share a common aetiology.
      Associations with lower socio-economic status highlight the potential influence
      of family background factors in feeding problems in the preterm infant.

PMID- 23952200
TI  - II. NIH Toolbox Cognition Battery (CB): measuring executive function and
      attention.
AB  - In this chapter, we discuss two measures designed to assess executive function
      (EF) as part of the NIH Toolbox Cognition Battery (CB) and report pediatric data
      from the validation study. EF refers to the goal-directed cognitive control of
      thought, action, and emotion. Two measures were adapted for standardized computer
      administration: the Dimensional Change Card Sort (a measure of cognitive
      flexibility) and a flanker task (a measure of inhibitory control in the context
      of selective visual attention). Results reveal excellent developmental
      sensitivity across childhood, excellent reliability, and (in most cases)
      excellent convergent validity. Correlations between the new NIH Toolbox measures
      and age were higher for younger children (3-6 years) than for older children (8
      15 years), and evidence of increasing differentiation of EF from other aspects of
      cognition (indexed by receptive vocabulary) was obtained. 

PMID- 23952199
TI  - I. NIH Toolbox Cognition Battery (CB): introduction and pediatric data.
AB  - This monograph presents the pediatric portion of the National Institutes of
      Health (NIH) Toolbox Cognition Battery (CB) of the NIH Toolbox for the Assessment
      of Neurological and Behavioral Function. The NIH Toolbox is an initiative of the
      Neuroscience Blueprint, a collaborative framework through which 16 NIH
      Institutes, Centers, and Offices jointly support neuroscience-related research,
      to accelerate discoveries and reduce the burden of nervous system disorders. The
      CB is one of four modules that measure cognitive, emotional, sensory, and motor
      health across the lifespan. The CB is unique in its continuity across childhood,
      adolescence, early adulthood, and old age, and in order to help create a common
      currency among disparate studies, it is also available at low cost to researchers
      for use in large-scale longitudinal and epidemiologic studies. This chapter
      describes the evolution of the CB; methods for selecting cognitive subdomains and
      instruments; the rationale for test design; and a validation study in children
      and adolescents, ages 3-15 years. Subsequent chapters feature detailed
      discussions of each test measure and its psychometric properties (Chapters 2-6),
      the factor structure of the test battery (Chapter 7), the effects of age and
      education on composite test scores (Chapter 8), and a final summary and
      discussion (Chapter 9). As the chapters in this monograph demonstrate, the CB has
      excellent psychometric properties, and the validation study provided evidence for
      the increasing differentiation of cognitive abilities with age. 

PMID- 23952201
TI  - III. NIH Toolbox Cognition Battery (CB): measuring episodic memory.
AB  - One of the most significant domains of cognition is episodic memory, which allows
      for rapid acquisition and long-term storage of new information. For purposes of
      the NIH Toolbox, we devised a new test of episodic memory. The nonverbal NIH
      Toolbox Picture Sequence Memory Test (TPSMT) requires participants to reproduce
      the order of an arbitrarily ordered sequence of pictures presented on a computer.
      To adjust for ability, sequence length varies from 6 to 15 pictures. Multiple
      trials are administered to increase reliability. Pediatric data from the
      validation study revealed the TPSMT to be sensitive to age-related changes. The
      task also has high test-retest reliability and promising construct validity.
      Steps to further increase the sensitivity of the instrument to individual and age
      related variability are described. 

PMID- 23952202
TI  - IV. NIH Toolbox Cognition Battery (CB): measuring language (vocabulary
      comprehension and reading decoding).
AB  - Mastery of language skills is an important predictor of daily functioning and
      health. Vocabulary comprehension and reading decoding are relatively quick and
      easy to measure and correlate highly with overall cognitive functioning, as well
      as with success in school and work. New measures of vocabulary comprehension and
      reading decoding (in both English and Spanish) were developed for the NIH Toolbox
      Cognition Battery (CB). In the Toolbox Picture Vocabulary Test (TPVT),
      participants hear a spoken word while viewing four pictures, and then must choose
      the picture that best represents the word. This approach tests receptive
      vocabulary knowledge without the need to read or write, removing the literacy
      load for children who are developing literacy and for adults who struggle with
      reading and writing. In the Toolbox Oral Reading Recognition Test (TORRT),
      participants see a letter or word onscreen and must pronounce or identify it. The
      examiner determines whether it was pronounced correctly by comparing the response
      to the pronunciation guide on a separate computer screen. In this chapter, we
      discuss the importance of language during childhood and the relation of language
      and brain function. We also review the development of the TPVT and TORRT,
      including information about the item calibration process and results from a
      validation study. Finally, the strengths and weaknesses of the measures are
      discussed. 

PMID- 23952203
TI  - V. NIH Toolbox Cognition Battery (CB): measuring working memory.
AB  - This chapter focuses on the NIH Toolbox List Sorting Working Memory Test, which
      was developed to assess processing speed within the NIH Toolbox Cognition Battery
      (CB). This test is a sequencing task requiring children and adults to process
      stimuli (presented both visually and auditorily) and sequence the stimuli
      according to size. We describe the development of the NIH Toolbox List Sorting
      Working Memory Test, highlighting its utility in children. We examine descriptive
      data, test-retest reliability, and convergent and discriminant validity. Results
      indicated that List Sorting performance was positively correlated with age
      indicating that performance on the task improved throughout childhood and early
      adolescence. Further, test-retest reliability coefficients were high and there
      was support for both convergent and discriminant validity. These data suggest
      that the NIH Toolbox List Sorting Working Memory Test is reliable and shows
      evidence of construct validity. 

PMID- 23952204
TI  - VI. NIH Toolbox Cognition Battery (CB): measuring processing speed.
AB  - This chapter focuses on the Toolbox Pattern Comparison Processing Speed Test,
      which was developed to assess processing speed within the NIH Toolbox Cognition
      Battery (CB). We describe the development of the test, highlighting its utility
      in children. In addition, we examine descriptive data, test-retest reliability,
      validity, and preliminary work creating a composite index of processing speed.
      Results indicated that most children were able to understand the basic concepts
      of the Toolbox Pattern Comparison Processing Speed Test. Further, test-retest
      reliability was excellent. Analyses examining convergent and discriminant
      validity provided support for the utility of the test as a measure of processing
      speed. Finally, analyses comparing and combining scores on the Toolbox Pattern
      Comparison Processing Speed Test with other measures of simple reaction time from
      the NIH Toolbox CB indicated that a Processing Speed Composite score performed
      better than any test examined in isolation. Taken together, the Toolbox Pattern
      Comparison Processing Speed Test appears to exhibit a number of strengths: it is
      child-friendly and engaging, short and easy to administer, and has good construct
      validity, especially when used as part of a composite score. 

PMID- 23952205
TI  - VII. NIH Toolbox Cognition Battery (CB): factor structure for 3 to 15 year olds.
AB  - Confirmatory factor analysis was used the evaluate the dimensional structure
      underlying the NIH Toolbox Cognition Battery (CB) and the measures chosen to
      serve as concurrent validity criteria for the NIH Toolbox CB. These results were
      used to evaluate the convergent and discriminant validity of the CB in children
      ranging from 3 to 15 years of age. Results were evaluated separately for a 3- to
      6-year-old group and a 8- to 15-year-old group because different validation
      measures were used in these age groups. Three distinct dimensions were found for
      the 3- to 6-year-old group: Vocabulary, Reading, and Fluid Abilities. Five
      dimensions were found for 8-15 year olds: Vocabulary, Reading, Episodic Memory,
      Working Memory, and Executive Function/Processing Speed. CB measures and their
      validation analogues consistently defined common factors in a pattern that
      broadly supported the convergent and discriminant validity of the CB, but results
      showed higher intercorrelation and less differentiation of cognitive dimensions
      in younger than in older children and in older children compared with adults. Age
      was strongly related to the cognitive dimensions underlying test performance in
      both groups of children and results are consistent with broader literature
      showing increasing differentiation of cognitive abilities associated with the
      rapid brain development that occurs from early childhood into adulthood. 

PMID- 23952206
TI  - VIII. NIH Toolbox Cognition Battery (CB): composite scores of crystallized,
      fluid, and overall cognition.
AB  - The NIH Toolbox Cognition Battery (CB) includes 7 tests covering 6 cognitive
      abilities. This chapter describes the psychometric characteristics in children
      ages 3-15 years of a total summary score and composite scores reflecting two
      major types of cognition: "crystallized" (more dependent upon past learning
      experiences) and "fluid" (capacity for new learning and information processing in
      novel situations). Both types of cognition are considered important in everyday
      functioning, but are thought to be differently affected by brain health status
      throughout life, from early childhood through older adulthood. All three Toolbox
      composite scores showed excellent test-retest reliability, robust developmental
      effects across the childhood age range considered here, and strong correlations
      with established measures of similar abilities. Additional preliminary evidence
      of validity includes significant associations between all three Toolbox composite
      scores and maternal reports of children's health status and school performance. 

PMID- 23952207
TI  - IX. NIH Toolbox Cognition Battery (CB): summary, conclusions, and implications
      for cognitive development.
AB  - This monograph describes the creation of the National Institutes of Health
      Toolbox Cognition Battery (NIH Toolbox CB) and reports validation data for
      children ages 3-15 years. Individual chapters described measures of executive
      function, episodic memory, language, working memory, speed of processing, and
      attention. Separate chapters were devoted to the factor structure of the test
      battery and composite measures of cognitive health (Total Composite, Fluid
      Composite, Crystallized Composite). In all cases, the NIH Toolbox CB measures
      showed sensitivity to age-related changes across the 3- to 15-year range as well
      as test/retest reliability. The measures also demonstrated adequate to excellent
      convergent validity, and there was evidence of greater discriminant validity
      among older than younger children. Confirmatory factor analyses revealed five-
      and three-factor models for the older (8-15 year olds) and younger (3-6 year
      olds) children, respectively. The correlation between the Fluid and Crystallized
      Composite scores was higher among the younger than the older children. The
      overall pattern is suggestive of greater differentiation of cognitive abilities
      with age. The strong psychometric properties of the CB and its apparent
      sensitivity to patterns of developmental change suggest that it is an important
      advance in the study of cognitive development and has the potential to
      substantially accelerate discoveries through use of common methods across
      disparate laboratories and even disciplines. 

PMID- 23952209
TI  - Commentary on Zelazo and Bauer (editors), National Institutes of Health Toolbox
      Cognition Battery (CB): validation for children between 3 and 15 years.

PMID- 23952214
TI  - Utility and importance of accurate Hb A2 measurements for defining a strategy for
      beta-thalassemia screening: experience in the Balearic Islands, Spain.
AB  - The high heterogeneity in regional profiles of beta-thalassemia (beta-thal)
      mutations highlights the need for population-specific carrier detection
      strategies. Our aim was to analyze the relationship between hematological values
      and beta(0) and beta(+) mutations in 154 Balearic beta-thal heterozygotes, in
      order to establish the most optimized mutation carrier detection strategy to be
      used to manage the disease in our population. The Hb A2 level was the best
      parameter for discriminating between both types of carriers. Taking into account
      the cut-off point value of 4.85% (Hb A2), obtained by a receiver-operating
      characteristic (ROC) curve analysis, we proposed an algorithm that would use a
      real-time polymerase chain reaction (RT-PCR) hybridization probe assay technique
      to detect one of the two most common mutations in the Balearic population, namely
      codon 39 (C>T) and IVS-I-110 (G>A), depending on the Hb A2 value of the patient. 

PMID- 23952213
TI  - A novel role of PR2 in abscisic acid (ABA) mediated, pathogen-induced callose
      deposition in Arabidopsis thaliana.
AB  - Pathogenesis-related protein 2 (PR2) is known to play a major role in plant
      defense and general stress responses. Resistance against the fungal pathogen
      Leptosphaeria maculans in Arabidopsis requires abscisic acid (ABA), which
      promotes the deposition of callose, a beta-1,3-glucan polymer. Here, we examined
      the role of PR2 in callose deposition in relation to ABA treatment and challenge
      with L. maculans and Pseudomonas syringae. Characterization of PR2-overexpressing
      plants and the knockout line indicated that PR2 negatively affects callose
      deposition. Recombinant PR2 purified from Pichia pastoris showed callose
      degrading activity, and a considerable reduction in the callose-degrading
      activity was observed in the leaf extract of the PR2 knockout line compared with
      the wild-type. ABA pretreatment before challenge with L. maculans concomitantly
      repressed PR2 and enhanced callose accumulation. Likewise, overexpression of an
      ABA biosynthesis gene NCED3 resulted in reduced PR2 expression and increased
      callose deposition. We propose that ABA promotes callose deposition through the
      transcriptional repression of PR2 in Arabidopsis challenged by L. maculans and P.
      syringae. Callose by itself is likely to act antagonistically on salicylic acid
      (SA) defense signaling, suggesting that PR2 may function as a modulator of
      callose- and SA-dependent defense responses. 

PMID- 23952215
TI  - Evaluating gene expression profiling by quantitative polymerase chain reaction to
      develop a clinically feasible test for outcome prediction in multiple myeloma.
AB  - The gene expression profiles (GEPs) of 96 selected genes were analysed by real
      time quantitative polymerase chain reaction (qPCR) with a TaqMan low-density
      array card in isolated tumour plasma cells (PCs) from 157 newly diagnosed
      multiple myeloma (MM) patients. This qPCR-based GEP correctly classified cases
      following the Translocation-cyclin D classification. Classic prognostic
      parameters and qPCR-based GEP predicted MM patient outcome and, although
      multivariate analyses revealed that cytogenetic risk (standard vs. high risk) was
      the variable that most strongly predicted prognosis, GEP added significant
      information for risk stratification. Considering only the standard risk
      cytogenetic patients, multivariate analyses revealed that high beta2
      microglobulin, low CDKN1A and high SLC19A1 gene expression levels independently
      predicted a short time-to-progression (TTP), while high International Staging
      System stage, low CDKN2B and high TBRG4 gene expression predicted poor overall
      survival (OS). A gene expression risk score enabled the division of standard risk
      patients into two groups with different TTPs (83% vs. 38% at 3 years, P < 0.0001)
      and OS rates (88% vs. 61% at 5 years; P = 0.003). This study demonstrates that
      quantitative PCR is a robust, accurate and feasible technique for implementing in
      the daily routine as a surrogate for GEP-arrays. 

PMID- 23952216
TI  - LL-37 in periodontal health and disease and its susceptibility to degradation by
      proteinases present in gingival crevicular fluid.
AB  - AIM: To determine the levels of LL-37 in and its susceptibility to degradation by
      components of gingival crevicular fluid (GCF) in periodontal health and disease.
      MATERIALS AND METHODS: Levels of LL-37 in GCF from periodontitis patients and
      periodontally healthy subjects were determined by ELISA. In addition, degradation
      of synthetic/exogenous LL-37 by components of GCF in the presence and absence of
      inhibitors was determined by matrix-assisted laser desorption/ionization time of
      flight mass spectrometry. RESULTS: The concentration of native LL-37 in GCF from
      Porphyromonas gingivalis positive (Pg+) and P. gingivalis negative (Pg-) sites in
      periodontitis patients was significantly higher than in GCF from healthy
      subjects. When synthetic LL-37 was added to healthy GCF, the peptide was not
      degraded. Conversely, GCF from Pg+ sites rapidly degraded synthetic LL-37 which
      was prevented in the presence of Arg- and Lys- gingipain inhibitors. Synthetic LL
      37 was degraded more slowly by GCF from Pg- sites. CONCLUSIONS: LL-37 is
      detectable in GCF in periodontal health and disease. The rapid degradation of
      synthetic LL-37 in periodontitis GCF, particularly in Pg+ sites, limits its role
      as a potential therapeutic in the gingival crevice. These results highlight the
      need to design stable peptide mimetics of LL-37 as future therapeutics in
      periodontitis.

PMID- 23952217
TI  - Mechanism and selectivity in nickel-catalyzed cross-electrophile coupling of aryl
      halides with alkyl halides.
AB  - The direct cross-coupling of two different electrophiles, such as an aryl halide
      with an alkyl halide, offers many advantages over conventional cross-coupling
      methods that require a carbon nucleophile. Despite its promise as a versatile
      synthetic strategy, a limited understanding of the mechanism and origin of cross
      selectivity has hindered progress in reaction development and design. Herein, we
      shed light on the mechanism for the nickel-catalyzed cross-electrophile coupling
      of aryl halides with alkyl halides and demonstrate that the selectivity arises
      from an unusual catalytic cycle that combines both polar and radical steps to
      form the new C-C bond. 

PMID- 23952218
TI  - Influence of ionic strength on triplet-state natural organic matter loss by
      energy transfer and electron transfer pathways.
AB  - Triplet state excited natural organic matter chromophores ((3)NOM*) are important
      reactive intermediates in indirect photochemical processes, yet the impact of
      salt concentrations relevant to estuarine and marine environments on (3)NOM* is
      poorly understood. The formation rates, pseudo-first-order loss rate constants,
      and steady-state concentration of (3)NOM* were monitored using the sorbate probe
      method in synthetic matrices with increasing ionic strength (IS) to seawater
      values using seawater halides or other salts. The steady-state concentration of
      (3)NOM* approximately doubled at seawater IS, regardless of the salt used, due to
      a decrease in the (3)NOM* decay rate constant. The electron transfer-mediated
      degradation of 2,4,6-trimethylphenol (TMP) by (3)NOM* was significantly slowed at
      higher IS. A model is proposed wherein high IS slows intra-organic matter
      electron transfer pathways, an important (3)NOM* loss pathway, leading to longer
      (3)NOM* lifetimes. Although IS did not appear to impact energy transfer pathways
      directly, the higher (3)NOM* steady-state concentrations promote energy transfer
      interactions. The observed decrease in decay rate constant, increase in steady
      state concentration of (3)NOM* at high IS, and the inhibition of electron
      transfer pathways should be considered when determining the fate of organic
      pollutants in estuarine and marine environments. 

PMID- 23952219
TI  - Conformationally constrained lipid A mimetics for exploration of structural basis
      of TLR4/MD-2 activation by lipopolysaccharide.
AB  - Recognition of the lipopolysaccharide (LPS), a major component of the outer
      membrane of Gram-negative bacteria, by the Toll-like receptor 4 (TLR4)-myeloid
      differentiation factor 2 (MD-2) complex is essential for the control of bacterial
      infection. A pro-inflammatory signaling cascade is initiated upon binding of
      membrane-associated portion of LPS, a glycophospholipid Lipid A, by a coreceptor
      protein MD-2, which results in a protective host innate immune response. However,
      activation of TLR4 signaling by LPS may lead to the dysregulated immune response
      resulting in a variety of inflammatory conditions including sepsis syndrome.
      Understanding of structural requirements for Lipid A endotoxicity would ensure
      the development of effective anti-inflammatory medications. Herein, we report on
      design, synthesis, and biological activities of a series of conformationally
      confined Lipid A mimetics based on beta,alpha-trehalose-type scaffold.
      Replacement of the flexible three-bond beta(1->6) linkage in diglucosamine
      backbone of Lipid A by a two-bond beta,alpha(1<->1) glycosidic linkage afforded
      novel potent TLR4 antagonists. Synthetic tetraacylated bisphosphorylated Lipid A
      mimetics based on a beta-GlcN(1<->1)alpha-GlcN scaffold selectively block the LPS
      binding site on both human and murine MD-2 and completely abolish
      lipopolysaccharide-induced pro-inflammatory signaling, thereby serving as
      antisepsis drug candidates. In contrast to their natural counterpart lipid IVa,
      conformationally constrained Lipid A mimetics do not activate mouse TLR4. The
      structural basis for high antagonistic activity of novel Lipid A mimetics was
      confirmed by molecular dynamics simulation. Our findings suggest that besides the
      chemical structure, also the three-dimensional arrangement of the diglucosamine
      backbone of MD-2-bound Lipid A determines endotoxic effects on TLR4. 

PMID- 23952220
TI  - Serum uric acid levels correlate with benign paroxysmal positional vertigo.
AB  - BACKGROUND AND PURPOSE: Benign paroxysmal positional vertigo (BPPV) is a
      frequently encountered condition that can severely affect the quality of life. In
      this study, we aimed to assess the possible relations between serum uric acid
      (SUA) levels and BPPV. METHODS: Fifty patients with BPPV, and 40 age- and sex
      matched control subjects were enrolled in the study. All the patients and
      controls underwent a complete audio-vestibular test battery including the Dix
      Hallpike maneuver and supine roll test for posterior semicircular canal (PSC) and
      horizontal semicircular canal, respectively. Routine hematological and
      biochemical analyses were performed in both groups. In the BPPV group,
      measurements of SUA levels were repeated 1 month after the vertigo attack.
      RESULTS: The lipid profiles and SUA levels were higher in patients with BPPV than
      detected in controls (P < 0.05 and P < 0.001, respectively). Albumin and SUA
      values were independently associated with BPPV in multiple logistic regression
      models (P < 0.05 and P < 0.001, respectively). A cutoff value of 4 for SUA level
      with a sensitivity of 0.72 (0.58-0.84) and a specificity of 0.60 (0.43-0.75) was
      obtained in the receiver operating characteristic analyses. There was a
      significant decrement in SUA level 1 month after the vertigo attack compared with
      the values obtained during the attack (P < 0.001). Among the most involved type
      of BPPV (PSC BPPV), the right side was affected in 26 patients (57.8%) and the
      left side in 19 patients (42.2%). SUA levels did not differ statistically in
      patients with PSC BPPV for either the right or left sides (P > 0.05).
      CONCLUSIONS: Elevated SUA is positively correlated with BPPV, requiring further
      efforts to clarify the exact mechanism.

PMID- 23952221
TI  - From the editor's desk.
AB  - No abstract available for this article. 

PMID- 23952222
TI  - From another perspective.
AB  - In reacting to the articles in this publication, several issues are raised and
      discussed. Some of these are philosophical in nature, others are somewhat more
      pragmatic. Although presented within the context of community based practice, the
      issues raised are pertinent to the profession in general. 

PMID- 23952223
TI  - After treatment what?
AB  - Until very recently, occupational therapy services have been provided in
      institutional settings and have followed the medical model. The escalating costs
      of hospital care have been the primary incentives for moving patients out of
      acute settings and thus increasing the need for occupational therapy services in
      the community. Yet, relatively few therapists have moved from the medical model
      even though the need exists and legislation encourages that service be provided
      in the least restrictive alternative. Further, occupational therapists have been
      slow to adopt distinct strategies for planning with patients for their roles and
      needs after treatment even though the heart of the occupational therapy
      philosophy centers on adaptation to life roles. This paper explores the current
      trends away from institution-based health care and towards a continuum of health
      and social services, and the roles for occupational therapists in community
      settings. Occupational therapists are urged to act as facilitators in assisting
      patients to move successfully from active treatment to independence in whatever
      settings they find themselves. 

PMID- 23952224
TI  - Are you ready?
AB  - A discharge planning group designed and facilitated by occupational therapy staff
      in an acute psychiatric treatment setting is described. The purpose of the group
      is to involve patients in their plans for leaving the hospital and to smooth
      their transition to the settings to which they are going. Other members of the
      team, nurses, social workers, as well as psychiatrists, are involved in
      implementing this program. In this presentation, the procedures used in the group
      are described, case examples of two patients are discussed, and suggestions for
      generalizing this model of group process to other settings are made. 

PMID- 23952225
TI  - The home visit.
AB  - The home visit has become a integral part of treatment programs for a large
      number of patients at the Spaulding Rehabilitation Hospital. It is especially
      useful for elderly patients, who represent a considerable share of the caseload,
      and has proven to be most beneficial for those individuals who are returning home
      to live alone or be alone part of the day. At Spaulding the hyome visit is most
      often conducted by an occupational and physical therapist team who follow a
      specific evaluation protocol examining the patient's home environment vis-a-vis
      anticipated functional status at discharge. Recommendations and suggestions for
      both use patterns and possible structural changes follow. In order to both
      evaluate the process and the results of home visits a chart audit was conducted
      from which various ways have been discovered to improve the value of this
      treatment activity and thereby enhance a patient's quality of life after
      discharge. 

PMID- 23952226
TI  - Home care occupational therapy.
AB  - This paper describes the Home Health Care Department at Loma Linda University
      Medical Center (LLUMC). Responsibilities of the staff occupational therapists are
      outlined. Homebound criteria are noted and benefits of home health care
      illustrated. Equipment and supplies necessary are listed and examples are given
      of substitutions for or adaptations to commercially available equipment. 

PMID- 23952227
TI  - Family stroke education.
AB  - To increase families' involvement in rehabilitation, an informational session
      called Family Stroke Education Class was implemented at a 305 bed medical center
      serving disabled veterans and their families. After a year, a study of
      questionnaires completed by family and patients at the meetings showed that
      anxiety level about their illness had decreased significantly. Twenty-six (86.7
      percent) of thirty participants felt more comfortable about approaching team
      members with questions in the future, and 76.7 percent felt more informed as a
      result of taking the class. Knowledge scores improved significantly on the post
      tests. Thus it appears that the educational format is a practical way of
      including the needs and soliciting participation of families as well as a means
      for providing basic information to patients on stroke rehabilitation. 

PMID- 23952228
TI  - Occupational therapy care of rheumatic disease patients.
AB  - The purpose of this evaluation was to determine if the level of independence
      achieved in self-care, home, and community skills at time of discharge from an
      inpatient occupational therapy program was maintained up to one year post
      discharge. With the use of a structured interview form, a trained volunteer
      telephoned patients at three, six, and twelve months post-discharge. Of the 363
      patients followed, 86% and 97% reported that they maintained or increased their
      levels of independence. This suggests that there was effective carryover of
      functional skills into the home and community. 

PMID- 23952229
TI  - The effects of program termination on community participation by developmentally
      disabled adults.
AB  - Funding cuts in health care programs are now commonplace, and result in
      termination of many valuable and needed services. One such program so affected
      which served adults with developmental disabilities inspired a follow-up study to
      see the effect of loss of the program on the clients it had served. Board and
      care facilities served by the habilitation program were rivisited one year later,
      and interviews were held with past participants to identify their current
      involvement in community activities and how they felt about closure of the former
      program. The findings point to the importance of the "benefactors" in the initial
      adjustment to community living and to the need for continued or extended support
      for individuals who have experienced long-term institutionalization. 

PMID- 23952230
TI  - Options for placement.
AB  - Most older people and families are unfamiliar with long-term care options. Many
      of them, when faced with the prospects of out-of-home placement, need assistance
      in understanding, accessing, and impacting the long-term care system. This
      article describes a unique placement service developed by an occupational
      therapist to assist older persons and families to (1) identify the
      appropriateness of out-of-home placement, (2) determine the level of care needed,
      and (3) obtain specific information about long-term care facilities in the
      community, in order to make informed choices about appropriate sheltered living
      environments and care facilities. 

PMID- 23952231
TI  - Independent living programs.
AB  - Helping patients achieve independent living status or "maximum independence" is
      the goal of occupational therapy. Until recently, however, "independence"
      achieved during treatment programs was frequently lost outside of the health care
      institution because of restrictive or even hostile environments to which patients
      moved. Now as a result of cooperative advocacy, disabled persons and
      professionals, aided by useful legisltation, have developed and implemented new
      models of services to promote independent living. Central to independent living
      programs is a philosophy of consumer participation, self-determination and having
      control over one's life by those who are served. This paper presents a brief
      history of the independent living movement. It then defines and discusses three
      models commonly seen and gives examples of the servicess they provide. It
      concludes with a consideration of the factors that influence the success of the
      transition of persons moving from medical to independent living settings. 

PMID- 23952232
TI  - Work related programs in occupational therapy.
AB  - This paper addresses occupational therapists who would like to become involved in
      work related programs for the industrially injured. The authors review the
      historical and philosophical bases that support occupational therapy's use of
      work as an evaluative and therapeutic medium. The workers' compensation process
      is outlined and key professionals in the system are identified. Three services
      that the occupational therapist can provide are defined. They are work tolerance
      screening, work capacity evaluation, and work hardening. An example of basic
      program structure, including evaluative tools, is given for each of the three
      services. 

PMID- 23952233
TI  - Industry and injuries.
AB  - The purpose of this article is to give a brief historical review and description
      of the private, for-profit rehabilitation industry in order to describe how
      occupational therapists can provide a valuable and cost effective service to
      injured workers, as well as to insurance carriers, physicians, and vocational
      specialists. A single case will be presented to illustrate how occupational
      therapists can function in this new element of rehabilitation. 

PMID- 23952234
TI  - Community.
AB  - Occupational therapy program development in times of scarce funding can be
      difficult, if not impossible, despite demonstrated need. This paper describes the
      strategies in one facility when staff looked to their community and to specific
      external sources of support in order to achieve program objectives. The facility
      and its programs will be described, as they expanded and developed, including
      examples of specific ways in which various persons and businesses in the
      surrounding neighborhoods were tapped to provide needed resources for training
      programs for special needs children, adolescents and young adults. In so doing,
      this staff also provided realistic avenues for successful adaptation of their
      students after they left the training school. 

PMID- 23952235
TI  - Competitive sports for the disabled athlete.
AB  - No abstract available for this article. 

PMID- 23952236
TI  - The sit-straightTM cushion.
AB  - No abstract available for this article. 

PMID- 23952238
TI  - One-pot synthesis of substituted benzo[b]furans from mono- and dichlorophenols
      using palladium catalysts bearing dihydroxyterphenylphosphine.
AB  - A dihydroxyterphenylphosphine bearing cyclohexyl groups on the phosphorus atom
      (Cy-DHTP) was found to be a powerful ligand for the palladium-catalyzed one-pot
      synthesis of substituted benzo[b]furans from 2-chlorophenols and terminal
      alkynes. This catalyst system was also applicable to the sequential one-pot
      synthesis of disubstituted benzo[b]furans from dichlorophenols via the Suzuki
      Miyaura cross-coupling of chlorobenzo[b]furan with boronic acids. The use of two
      ligands, Cy-DHTP and XPhos, is the key to promoting the reactions. Mechanistic
      studies suggest that the Pd-Cy-DHTP catalyst is the active species in the
      Sonogashira cross-coupling step, while the Pd-XPhos catalyst accelerates the
      Suzuki-Miyaura cross-coupling step. 

PMID- 23952237
TI  - Characterization and modeling of the oligomeric state and ligand binding behavior
      of purified translocator protein 18 kDa from Rhodobacter sphaeroides.
AB  - Translocator Protein 18 kDa (TSPO), previously known as the peripheral-type
      benzodiazepine receptor (PBR), is a mitochondrial outer membrane protein that has
      been identified as a key player in cholesterol and porphyrin transport, apoptotic
      signaling, and cancer development, as well as neurological inflammation and
      disease. Despite a number of TSPO ligands whose effects have been studied with
      respect to these varied biological activities, the nature of their interactions
      with TSPO and the molecular mechanism of their effects remain controversial, in
      part because of the lack of an atomic-resolution structure. We expressed and
      purified the homologue of mammalian TSPO from Rhodobacter sphaeroides (RsTSPO),
      as well as a mutant form in a proposed drug binding loop, RsTSPOW38C. We
      characterized their binding behaviors with endogenous ligands and a series of
      compounds that affect apoptosis by using a sensitive tryptophan fluorescence
      quenching assay. Our results show that RsTSPO behaves as a dimer in the purified
      state and binds with low micromolar affinity to many of these ligands, including
      retinoic acid, curcumin, and a known Bcl-2 inhibitor, gossypol, suggesting a
      possible direct role for TSPO in their regulation of apoptosis. A computational
      model of the RsTSPO dimer is constructed using EM-Fold, Rosetta, and a cryo
      electron microscopy density map. Binding behaviors of known ligands are discussed
      in the context of the model with respect to regions that may be involved in
      binding. 

PMID- 23952239
TI  - Ontogenetic variation in epibiont community structure in the deep-sea yeti crab,
      Kiwa puravida: convergence among crustaceans.
AB  - Recent investigations have demonstrated that unusually 'hairy' yeti crabs within
      the family Kiwaidae associate with two predominant filamentous bacterial
      families, the Epsilon and Gammaproteobacteria. These analyses, however, were
      based on samples collected from a single body region, the setae of pereopods. To
      more thoroughly investigate the microbiome associated with Kiwa puravida, a yeti
      crab species from Costa Rica, we utilized barcoded 16S rRNA amplicon
      pyrosequencing, as well as microscopy and terminal restriction fragment length
      polymorphism analysis. Results indicate that, indeed, the bacterial community on
      the pereopods is far less diverse than on the rest of the body (Shannon indices
      ranged from 1.30-2.02 and 2.22-2.66, respectively). Similarly, the bacterial
      communities associated with juveniles and adults were more complex than
      previously recognized, with as many as 46 bacterial families represented.
      Ontogenetic differences in the microbial community, from egg to juvenile to
      adult, included a dramatic under-representation of the Helicobacteraceae and
      higher abundances of both Thiotrichaceae and Methylococcaceae for the eggs, which
      paralleled patterns observed in another bacteria-crustacean symbiosis. The degree
      to which abiotic and biotic feedbacks influence the bacterial community on the
      crabs is still not known, but predictions suggest that both the local environment
      and host-derived factors influence the establishment and maintenance of microbes
      associated with the surfaces of aquatic animals. 

PMID- 23952240
TI  - Self-assembled carbon nanotube honeycomb networks using a butterfly wing template
      as a multifunctional nanobiohybrid.
AB  - Insect wings have many unique and complex nano/microstructures that are presently
      beyond the capabilities of any current technology to reproduce them artificially.
      In particular, Morpho butterflies are an attractive type of insect because their
      multifunctional wings are composed of nano/microstructures. In this paper, we
      show that carbon nanotube-containing composite adopts honeycomb-shaped networks
      when simply self-assembled on Morpho butterfly wings used as a template. The
      unique nano/microstructure of the composites exhibits multifunctionalities such
      as laser-triggered remote-heating, high electrical conductivity, and repetitive
      DNA amplification. Our present study highlights the important progress that has
      been made toward the development of smart nanobiomaterials for various
      applications such as digital diagnosis, soft wearable electronic devices,
      photosensors, and photovoltaic cells. 

PMID- 23952242
TI  - The synthesis of indoline and benzofuran scaffolds using a Suzuki-Miyaura
      coupling/oxidative cyclization strategy.
AB  - The generation of indolines and benzofurans from the combination of Suzuki
      Miyaura coupling reactions with oxidative cyclizations is described. 

PMID- 23952244
TI  - ASXL1 mutations are infrequent in young patients with primary acute myeloid
      leukemia and their detection has a limited role in therapeutic risk
      stratification.
AB  - ASXL1 mutations are recurrent in acute myeloid leukemia (AML), but it is unclear
      whether ASXL1 genotype might influence patient management. We analyzed frequency
      and impact in younger (15-59 years) and older (>= 60 years) patients with primary
      or secondary disease. Overall, 9% had truncating mutations. Incidence was
      significantly lower in younger patients with primary than with secondary disease
      (4%, 12%; p = 0.03). In older patients it did not differ significantly (11%, 15%;
      p = 0.5). In univariate analysis, ASXL1-mutated patients had a worse outcome (5
      year relapse 83% vs. 56%, p = 0.01; overall survival [OS] 6% vs. 22%, p = 0.02).
      However in multivariate analysis, ASXL1 mutations had no prognostic significance
      (for OS, p = 0.3), because age was a major confounding factor. The low incidence
      of mutations in younger patients with primary disease and the lack of
      significance in multivariate analysis indicate that there is a limited role for
      screening at diagnosis for ASXL1 mutations for the purpose of prognostic
      stratification.

PMID- 23952243
TI  - Phase I study of azacitidine and bortezomib in adults with relapsed or refractory
      acute myeloid leukemia.
AB  - We previously reported that bortezomib indirectly modulates transcription of DNA
      methyltransferase 1 (DNMT). We designed a phase I study of azacitidine (a direct
      DNMT inhibitor) plus bortezomib in acute myeloid leukemia (AML) to determine
      safety and tolerability. Twenty-three adults with relapsed/refractory AML
      received azacitidine 75 mg/m(2) daily on days 1-7. Bortezomib was dose escalated
      from 0.7 mg/m(2) on days 2 and 5 to 1.3 mg/m(2) on days 2, 5, 9 and 12. The
      target dose was reached without dose limiting toxicities. Infection and/or
      febrile neutropenia were frequent. Patients received a median of 2 cycles of
      therapy (range, 1-12+). Five of 23 patients achieved remission, including two
      with morphologic and cytogenetic complete response (CR) and three with CR and
      incomplete count recovery (CRi). Of CR/CRi responders with cytogenetic
      abnormalities at baseline, three of four achieved cytogenetic CR. The combination
      of azacitidine and bortezomib was tolerable and active in this cohort of poor
      risk previously treated patients with AML.

PMID- 23952245
TI  - Erythroid but not cytogenetic response in a case with 5q- syndrome: a delayed
      effect of lenalidomide or a consequence of deferasirox treatment?

PMID- 23952246
TI  - Results of treatment with azacitidine in patients aged >= 75 years included in
      the Spanish Registry of Myelodysplastic Syndromes.
AB  - The tolerability of azacitidine (AZA) allows its administration in elderly
      patients. The objective of this study was to analyze the clinical and biological
      characteristics, transfusion independence (TI), overall survival (OS) and
      toxicity in a series of 107 patients >= 75 years of age from the Spanish Registry
      of Myelodysplastic Syndromes (MDS) treated with AZA. The median age (range) was
      78 (75-90) years. According to the World Health Organization (WHO)
      classification, 86/102 (84%) had MDS, 10/102 (10%) had mixed
      myeloproferative/myelodysplastic disorder and 6/102 (6%) had acute myeloblastic
      leukemia. Regarding MDS by the International Prognostic Scoring System on
      initiation of AZA, 38/84 (45%) were low-intermediate-1 risk and 46/84 (55%) were
      intermediate-2-high risk. Ninety-five patients (89%) were red blood cell or
      platelet transfusion dependent. The AZA schedule was 5-0-0 in 39/106 (37%)
      patients, 5-2-2 in 36/106 (34%) patients and 7 consecutive days in 31/106 (29%)
      patients. The median number of cycles administered was 8 (range, 1-30). Thirty
      eight out of 94 (40%) patients achieved TI. Median OS (95% confidence interval
      [CI]) was significantly better in patients achieving TI (n = 38) compared to
      patients who did not (n = 56) (22 [20.1-23.9] months vs. 11.1 [4.8-17.5] months,
      p = 0.001). No significant differences were observed in TI rate and OS among the
      three different schedules. With a median follow-up of 14 (min-max, 1-50) months,
      the median OS (95% CI) of the 107 patients was 18 (12-23) months and the
      probability of OS (95% CI) at 2 years was 34% (22-46%). Cycles were delayed in
      31/106 (29%) patients and 47/101 patients (47%) were hospitalized for infection.
      These results show that treatment with AZA was feasible and effective in this
      elderly population, with 40% achieving TI, having a better OS than patients not
      achieving it. The schedule of AZA administration did not affect efficacy and
      toxicity.

PMID- 23952247
TI  - Gene translocations in testicular lymphomas.

PMID- 23952248
TI  - Intraobserver reliability of posturography in patients with vestibular neuritis.
AB  - The aim of the study was to establish the intraobserver reliability of a
      posturographic method in patients (n = 34) with vestibular neuritis. Intraclass
      correlation coefficients (relative reliability) for all parameters and test
      positions (ALL(mean)) ranged from 0.71 (95% CI: 0.41-0.85) to 0.92 (95% CI: 0.84
      0.96). Absolute reliability (coefficient of variation) ranged between 3.1% (95%
      CI: 2.60-8.67) and 42.3% (95% CI: 40.7-74.5). Reliability of single test
      positions is much lower. The posturographic system showed good relative and
      satisfactory absolute intraobserver reliability for ALL(mean).

PMID- 23952249
TI  - Age differences in ethanol discrimination: acquisition and ethanol dose
      generalization curves following multiple training conditions in adolescent and
      adult rats.
AB  - BACKGROUND: Adolescents and adults vary in sensitivity to many effects of ethanol
      (EtOH), although it is unknown whether they also differ in their perception of
      EtOH's subjective cues. This study characterized EtOH discrimination in
      adolescent and adult male rats using a rapidly acquired Pavlovian conditioned
      approach procedure. METHODS: EtOH at 1 of the 3 training doses (0.75, 1.0, or
      1.25 g/kg) served as either a positive (POS) or negative (NOS) occasion setter.
      Each 20-minute training session consisted of eight 15-second presentations of 2
      cue lights located on either side of a dipper delivering chocolate Boost((r)) .
      For POS-trained rats, the cue lights reliably predicted 5-second presentations of
      chocolate Boost during EtOH but not saline sessions, with the opposite
      contingencies used for NOS-trained rats. Anticipatory approach behavior (head
      entries into the reward delivery area) in the presence and absence of the cue
      lights was used to calculate discrimination scores on EtOH and saline sessions.
      Following acquisition, various doses of EtOH (0 to 1.5 g/kg) were administered to
      establish generalization curves. RESULTS: Although animals of both ages responded
      differentially on EtOH and saline sessions by the end of acquisition, adults met
      criterion more quickly and had higher discrimination scores during reinforced
      sessions than adolescents. Whereas adolescents failed to demonstrate any dose
      dependent responding during testing when trained with the 0.75 or 1.25 g/kg EtOH
      doses, adults demonstrated broader EtOH generalization during testing sessions
      following training with all 3 EtOH doses. Among adolescents trained with 1.0 g/kg
      EtOH, less generalization occurred relative to adults. CONCLUSIONS: Adolescents
      were less sensitive to EtOH's interoceptive effects, indicating that EtOH is
      likely a more salient cue for adults than for adolescents. These findings
      contribute to evidence that suggests adolescent-typical insensitivity to internal
      cues that typically limit EtOH consumption may contribute to the elevated intake
      commonly reported during this developmental period.

PMID- 23952250
TI  - Somatotype-variables related to muscle torque and power output in female
      volleyball players.
AB  - The purpose of this study was to investigate the relationship between somatotype,
      muscle torque, maximal power output and height of rise of the body mass centre
      measured in akimbo counter movement jump (ACMJ), counter movement jump (CMJ) and
      spike jump (SPJ), and power output measured in maximal cycle ergometer exercise
      bouts in female volleyball players. Fourteen players participated in the study.
      Somatotype was determined using the Heath-Carter method. Maximal muscle torque
      was measured under static conditions. Power output was measured in 5 maximal
      cycle ergometer exercise bouts, 10 s each, at increasing external loads equal to
      2.5, 5.0, 7.5, 10.0 and 12.5% of body weight (BW). All jump trials (ACMJ, SPJ and
      CMJ) were performed on a force plate. The mean somatotype of volleyball players
      was: 4.9-3.5-2.5. The value of the sum of muscle torque of the left upper
      extremities was significantly correlated only with mesomorphic component.
      Mesomorphic and ectomorphic components correlated significantly with values of
      maximal power measured during ACMJ and CMJ. Power output measured in maximal
      cycle ergometer exercise bouts at increasing external loads equal to 2.5, 5.0 and
      7.5% of BW was significantly correlated with endomorphy, mesomorphy and
      ectomorphy. 

PMID- 23952251
TI  - SES and race-ethnic differences in the stress-buffering effects of coping
      resources among young adults.
AB  - OBJECTIVES: This study assesses socioeconomic status (SES) and race-ethnic
      differences in the extent to which coping resources (social support and self
      esteem) buffer the negative impact of chronic stress on depressive symptoms.
      DESIGN: We analyze data from a large community-based sample of young adults (ages
      18-23) living in Miami-Dade County, Florida, USA (N = 1411). RESULTS: Study
      findings indicate that the stress-buffering effects of social support or self
      esteem do not vary by SES. However, independent of SES and other study controls,
      non-Hispanic whites experience greater stress-buffering effects from social
      support than African-Americans and African-Americans experience greater stress
      buffering effects from self-esteem than Cubans and Nicaraguans. CONCLUSION: In
      light of these results, we conclude that a greater understanding of racial and
      ethnic differences in mental health requires close attention to cultural
      transmissions of coping strategies within groups, which may be partly responsible
      for these differences in buffering effects.

PMID- 23952252
TI  - Neonatal Fc receptor and its role in the absorption, distribution, metabolism and
      excretion of immunoglobulin G-based biotherapeutics.
AB  - The neonatal Fc receptor (FcRn) is a heterodimeric membrane associated protein
      expressed in a variety of endothelial, epithelial and hematopoietic cells. FcRn
      regulates pH dependent intracellular trafficking of immunoglobulin G (IgG) and
      albumin, resulting in enhanced serum persistence and transcellular permeability
      of these proteins compared to other proteins of similar size. FcRn confers
      passive immunity during the early stages of life by facilitating maternal
      transmission of antibodies during gestation, and in some species during the
      neonatal period. The receptor continues to contribute to immunity beyond the
      perinatal period and throughout life by providing immunosurveillance in
      intestinal, pulmonary and genitourinary mucosa. In this capacity, FcRn
      facilitates bidirectional transport of IgG across mucosa and intracellular
      trafficking of antigen-antibody complexes in antigen presenting cells. Based on
      the functional roles of FcRn in regulating serum persistence and transcellular
      permeability, protein engineers have sought to exploit this receptor as a means
      of enhancing the absorption, distribution, metabolism and excretion (ADME) of IgG
      based therapeutics. In this review, the current state of knowledge regarding the
      structural, mechanistic and functional properties of FcRn, as they relate to the
      ADME of IgG-based therapeutics, are discussed. 

PMID- 23952253
TI  - Borderline versus bipolar: differences matter.

PMID- 23952254
TI  - Primary headaches and trigeminal neuralgia: neuropathic pain yes or not?
      Evidences from neurophysiological procedures.
AB  - Despite the fact that neurophysiological evaluation is not useful for primary
      headache diagnosis, the nociceptive system exploration through reflexes and
      evoked potentials procedures may give an aid in understanding the
      pathophysiological mechanism subtending pain. Neuropathic pain is caused by a
      lesion or disease of the somatosensory nervous system, which is supported by
      clinical evaluation and instrumental assessment by trigeminal and nociceptive
      reflexes and laser evoked potentials. The same methods, applied to migraine and
      cluster headache, together with evidences coming from structural and functional
      neuroimaging, excluded the neuropathic origin of pain, which is attaining to
      symptomatic and idiopathic trigeminal neuralgia, but confirmed a complex
      dysfunction of pain processing. Tension-type headache fits with a model of non
      nociceptive and non-neuropathic pain, subtended by a complex interaction of
      peripheral muscular and central neuronal factors. The presence of altered
      modulation of pain concurs with migraine and tension-type headache, and should be
      taken into account for the choice of the best therapeutic approach. 

PMID- 23952255
TI  - Pharmacodynamic evaluation of 4 angiotensin-converting enzyme inhibitors in
      healthy adult horses.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are used in horses
      with cardiovascular disorders despite the paucity of available data regarding
      their efficacy. HYPOTHESIS: The degree of serum ACE inhibition varies
      considerably between drugs. ANIMALS: Eight healthy adult horses. METHODS:
      Randomized prospective study. Horses were fasted overnight prior to receiving one
      of 4 ACE inhibitors intragastrically, administered at one of 2 dosages, using a
      randomized Latin square design (benazepril: 0.5 and 0.25 mg/kg; ramipril: 0.3 and
      0.1 mg/kg; quinapril: 0.25 and 0.125 mg/kg; perindopril: 0.1 and 0.05 mg/kg).
      Serum ACE activity was measured using a kinetic spectrophotometric method.
      RESULTS: There was a significant effect of drug and dosage on maximum ACE
      inhibition (I(max)), ACE inhibition 24 hours after administration (I(24h)), and
      area under the curve (AUC(0-48h)). Benazepril at 0.5 mg/kg resulted in
      significantly higher I(max) (86.9 +/- 7.0%) and I(24h) (60.3 +/- 7.9%) compared
      to the other drugs. There was a significant decrease in indirect blood pressure
      (BP) over time after administration of each drug, but differences in BP were not
      significantly different between drugs. Pharmacodynamic variables measured after
      administration of benazepril to horses with free access to hay were not
      significantly different from those obtained after fasting. Administration of
      benazepril orally once daily for 7 days did not result in a cumulative effect on
      ACE inhibition. CONCLUSIONS AND CLINICAL IMPORTANCE: Of the ACE inhibitors
      tested, oral benazepril (0.5 mg/kg) is the most effective at inhibiting serum ACE
      activity in healthy horses.

PMID- 23952256
TI  - Postural threat differentially affects the feedforward and feedback components of
      the vestibular-evoked balance response.
AB  - Circumstances may render the consequence of falling quite severe, thus maximising
      the motivation to control postural sway. This commonly occurs when exposed to
      height and may result from the interaction of many factors, including fear,
      arousal, sensory information and perception. Here, we examined human vestibular
      evoked balance responses during exposure to a highly threatening postural
      context. Nine subjects stood with eyes closed on a narrow walkway elevated 3.85 m
      above ground level. This evoked an altered psycho-physiological state,
      demonstrated by a twofold increase in skin conductance. Balance responses were
      then evoked by galvanic vestibular stimulation. The sway response, which
      comprised a whole-body lean in the direction of the edge of the walkway, was
      significantly and substantially attenuated after ~800 ms. This demonstrates that
      a strong reason to modify the balance control strategy was created and subjects
      were highly motivated to minimise sway. Despite this, the initial response
      remained unchanged. This suggests little effect on the feedforward settings of
      the nervous system responsible for coupling pure vestibular input to functional
      motor output. The much stronger, later effect can be attributed to an integration
      of balance-relevant sensory feedback once the body was in motion. These results
      demonstrate that the feedforward and feedback components of a vestibular-evoked
      balance response are differently affected by postural threat. Although a fear of
      falling has previously been linked with instability and even falling itself, our
      findings suggest that this relationship is not attributable to changes in the
      feedforward vestibular control of balance. 

PMID- 23952257
TI  - Public spirometry for primary prevention of COPD.
AB  - BACKGROUND: The most effective action for primary prevention of chronic
      obstructive lung disease is smoking cessation early enough. In secondary
      prevention, smokers with airway obstruction were more likely to quit smoking. The
      aim of this study was to evaluate the impact of a public spirometry on smoking
      habits in terms of primary prevention. METHODS: Spirometry with its medical
      analysis was offered to visitors of a local public event called 'Lange Nacht der
      Wissenschaften' ('Long night of sciences'). The impact of results on smoking
      habits was evaluated in all smokers with an anonymized questionnaire afterwards.
      RESULTS: Two hundred fifty-seven people with the median age of 30 years
      (interquartile range 22-46) were examined. Out of 44 current smokers (17.1%),
      only two individuals showed a prebronchodilator FEV1/forced vital capacity-value
      <0.7. Fourteen smokers stated to have an increased motivation to quit smoking
      whereas 28 smokers declared that their motivation to quit smoking was independent
      of spirometry result. These smokers were significantly younger (median age 28 vs.
      40 years, P = 0.025) without differences in spirometry results or smoking habits.
      CONCLUSION: In an unselected population with a high amount of younger adults,
      normal spirometry did not show a short-term benefit for primary prevention of
      chronic obstructive lung disease in terms of increasing motivation to quit
      smoking.

PMID- 23952258
TI  - Synthesis and modeling perspectives of rhizosphere priming.
AB  - The rhizosphere priming effect (RPE) is a mechanism by which plants interact with
      soil functions. The large impact of the RPE on soil organic matter decomposition
      rates (from 50% reduction to 380% increase) warrants similar attention to that
      being paid to climatic controls on ecosystem functions. Furthermore, global
      increases in atmospheric CO2 concentration and surface temperature can
      significantly alter the RPE. Our analysis using a game theoretic model suggests
      that the RPE may have resulted from an evolutionarily stable mutualistic
      association between plants and rhizosphere microbes. Through model simulations
      based on microbial physiology, we demonstrate that a shift in microbial metabolic
      response to different substrate inputs from plants is a plausible mechanism
      leading to positive or negative RPEs. In a case study of the Duke Free-Air CO2
      Enrichment experiment, performance of the PhotoCent model was significantly
      improved by including an RPE-induced 40% increase in soil organic matter
      decomposition rate for the elevated CO2 treatment--demonstrating the value of
      incorporating the RPE into future ecosystem models. Overall, the RPE is emerging
      as a crucial mechanism in terrestrial ecosystems, which awaits substantial
      research and model development.

PMID- 23952259
TI  - Excited state properties of diiron dithiolate hydrides: implications in the
      unsensitized photocatalysis of H2 evolution.
AB  - Density functional theory (DFT) and time-dependent DFT (TDDFT) have been used to
      investigate how visible light photons can excite an asymmetrically substituted
      diiron hydride, [Fe2(pdt)(MU-H)(CO)4dppv](+) (1(+), dppv = cis-1,2-C2H2(PPh2)2;
      pdt = 1,3-propanedithiolate), as well as the symmetric species [Fe2(pdt)(MU
      H)(CO)4(PMe3)2](+) (2(+)), which are the first photocatalysts of proton reduction
      operating without employing sensitizers (Wang, W.; Rauchfuss, T. B.; Bertini, L.;
      Zampella, G.; J. Am. Chem. Soc., 2012, 134, 4525). Theoretical results illustrate
      that the peculiar reactivity associated to the excited states of 1(+) and 2(+) is
      compatible with three different scenarios: (i) it can arise from the movement of
      the hydride ligand from fully bridging to semibridging/terminal coordination,
      which is expected to be more reactive toward protons; (ii) reactivity could be
      related to cleavage of a Fe-S bond, which implies formation of a transient Fe
      penta-coordinate species that would trigger a facile turnstile hydride
      isomerization, if lifetime excitation is long enough; (iii) also in line with a
      Fe-S bond cleavage is the possibility that after excited state decay, a highly
      basic S center is protonated so that a species simultaneously containing S
      H(delta+) and Fe-H(delta-) moieties is formed and, once reduced by a suitable
      electron donor, it can readily afford H2 plus an unprotonated form of the FeFe
      complex. This last possibility is consistent with (31)P NMR and IR solution data.
      All the three possibilities are compatible with the capability of 1(+) and 2(+)
      to perform photocatalysis of hydrogen evolving reaction (HER) without sensitizer.
      Moreover, even though it turned out difficult to discriminate among the three
      scenarios, especially because of the lack of experimental excitation lifetimes,
      it is worth underscoring that all of the three pathways represent a novelty
      regarding diiron carbonyl photoreactivity, which is usually associated with CO
      loss. Results provide also a rationale to the experimental observations which
      showed that the simultaneous presence of donor ligands (dppv in the case of 1(+))
      and a H ligand in the coordination environment of diiron complexes is a key
      factor to prevent CO photodissociation and catalyze HER. Finally, the comparison
      of photoexcitation behavior of 1(+) and 2(+) allows a sort of generalization
      about the functioning of such hydride species. 

PMID- 23952260
TI  - Acute thrombocytopenia in patients treated with amiodarone is caused by
      antibodies specific for platelet membrane glycoproteins.
AB  - Amiodarone has been implicated as a cause of thrombocytopenia but the responsible
      mechanism is unknown. We performed studies in three patients to characterize the
      pathogenesis of this complication. No amiodarone-dependent, platelet-reactive
      antibodies were identified using conventional serological techniques. However,
      water-insoluble amiodarone solubilized in methanol and diluted to 1.0 mg/ml in
      aqueous buffer reproducibly promoted binding of IgG antibodies in patient serum
      to platelets. Solid phase assays identified drug-dependent antibodies specific
      for platelet glycoproteins (GP)Ia/IIa (integrin alpha2 beta1 ) in each patient
      and a second antibody specific for GPIIb/IIIa (alphaII b beta3 integrin) in one
      patient. When studied by ion mobility analysis and transmission electron
      microscopy, the serologically active amiodarone preparation, a milky suspension,
      was found to consist of particles 2-30 nm in diameter, typical of a coacervate, a
      state characteristic of amiodarone in aqueous medium. The findings provide
      evidence that thrombocytopenia in the three patients studied was caused by drug
      dependent antibodies specific for platelet glycoproteins GPIa/IIa and/or
      GPIIb/IIIa. We postulate that, in vivo, amiodarone may become incorporated into
      occult lipophilic domains in platelet glycoproteins, producing structural
      modifications that are immunogenic in some individuals, and that the resulting
      antibodies can cause platelet destruction in a person taking this drug.

PMID- 23952261
TI  - Somatometric measurements, and clinical chemistry and hematology parameters in
      Tibetan macaque (Macaca thibetana).
AB  - BACKGROUND: Limited physiological data for Tibetan macaques are available at
      present. This study will provide more rationale for evaluating this species.
      METHODS: Thirty-seven Tibetan macaques (15 males and 22 females) were used in
      this study. Somatometric measurements, clinical chemistry and hematology
      parameters, insulin, and C-peptide were analyzed. RESULTS: Females had higher
      values of waist and waist hip ratio (WHR) than males in somatometric
      measurements. There were no significant differences between the two genders in
      hematology. Significant differences between males and females were only found for
      aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in
      biochemistry testing. In addition, females had higher fasting insulin and C
      peptide than males. There was a strongly positive correlation between age and
      some somatometric parameters. CONCLUSIONS: These physiological data will provide
      veterinarians and researchers with baseline values to evaluate experimental
      results using Tibetan macaques.

PMID- 23952262
TI  - Mobile phone radiation induces mode-dependent DNA damage in a mouse spermatocyte
      derived cell line: a protective role of melatonin.
AB  - PURPOSE: To evaluate whether exposure to mobile phone radiation (MPR) can induce
      DNA damage in male germ cells. MATERIALS AND METHODS: A mouse spermatocyte
      derived GC-2 cell line was exposed to a commercial mobile phone handset once
      every 20 min in standby, listen, dialed or dialing modes for 24 h. DNA damage was
      determined using an alkaline comet assay. RESULTS: The levels of DNA damage were
      significantly increased following exposure to MPR in the listen, dialed and
      dialing modes. Moreover, there were significantly higher increases in the dialed
      and dialing modes than in the listen mode. Interestingly, these results were
      consistent with the radiation intensities of these modes. However, the DNA damage
      effects of MPR in the dialing mode were efficiently attenuated by melatonin
      pretreatment. CONCLUSIONS: These results regarding mode-dependent DNA damage have
      important implications for the safety of inappropriate mobile phone use by males
      of reproductive age and also suggest a simple preventive measure: Keeping mobile
      phones as far away from our body as possible, not only during conversations but
      during 'dialed' and 'dialing' operation modes. Since the 'dialed' mode is
      actually part of the standby mode, mobile phones should be kept at a safe
      distance from our body even during standby operation. Furthermore, the protective
      role of melatonin suggests that it may be a promising pharmacological candidate
      for preventing mobile phone use-related reproductive impairments.

PMID- 23952263
TI  - Perinatal outcome in sickle cell anemia: a prospective study from India.
AB  - Sickle cell anemia, the homozygous genotype of sickle cell disease is one of the
      most common heritable diseases in the world. The Arab-Asian haplotype present in
      India is one of the least severe of all haplotypes. Many sickle cell anemia
      patients are now leading a symptom-free productive life due to hydroxyurea (HU)
      and better supportive care. Although pregnancy in sickle cell anemia patients is
      considered a high-risk category, it perinatal outcome is least studied,
      particularly among carriers of the Arab-Asian haplotype. Thus, the present
      prospective, randomized study was performed to assess the perinatal outcome in
      sickle cell anemia. Neonatal outcome such as low birth weight, perinatal
      mortality rate, special care newborn unit (SCNU) admission, intrauterine growth
      retardation (IUGR) and pre term births were significantly higher in sickle cell
      anemia mothers. Maternal outcome such as severe anemia, preeclampsia,
      vasoocclusive crisis (VOC), pulmonary complications, jaundice and blood
      transfusion requirements were significantly higher in sickle cell anemia mothers,
      which were successfully managed. Cesarian section rate was not significantly
      different from normal controls. Successful pregnancies were achieved in 84.44% of
      cases. However, we strongly recommend that pregnancies in these patients should
      be managed in an institutional setup. 

PMID- 23952264
TI  - Mechanisms of macroevolution: polyphagous plasticity in butterfly larvae revealed
      by RNA-Seq.
AB  - Transcriptome studies of insect herbivory are still rare, yet studies in model
      systems have uncovered patterns of transcript regulation that appear to provide
      insights into how insect herbivores attain polyphagy, such as a general increase
      in expression breadth and regulation of ribosomal, digestion- and detoxification
      related genes. We investigated the potential generality of these emerging
      patterns, in the Swedish comma, Polygonia c-album, which is a polyphagous, widely
      distributed butterfly. Urtica dioica and Ribes uva-crispa are hosts of P. c
      album, but Ribes represents a recent evolutionary shift onto a very divergent
      host. Utilizing the assembled transcriptome for read mapping, we assessed gene
      expression finding that caterpillar life-history (i.e. 2nd vs. 4th-instar
      regulation) had a limited influence on gene expression plasticity. In contrast,
      differential expression in response to host-plant identified genes encoding
      serine-type endopeptidases, membrane-associated proteins and transporters.
      Differential regulation of genes involved in nucleic acid binding was also
      observed suggesting that polyphagy involves large scale transcriptional changes.
      Additionally, transcripts coding for structural constituents of the cuticle were
      differentially expressed in caterpillars in response to their diet indicating
      that the insect cuticle may be a target for plant defence. Our results state that
      emerging patterns of transcript regulation from model species appear relevant in
      species when placed in an evolutionary context.

PMID- 23952267
TI  - From the editor's desk.
AB  - No abstract available for this article. 

PMID- 23952265
TI  - Testing the substrate-envelope hypothesis with designed pairs of compounds.
AB  - Acquired resistance to therapeutic agents is a significant barrier to the
      development of clinically effective treatments for diseases in which evolution
      occurs on clinical time scales, frequently arising from target mutations. We
      previously reported a general strategy to design effective inhibitors for rapidly
      mutating enzyme targets, which we demonstrated for HIV-1 protease inhibition
      [Altman et al. J. Am. Chem. Soc. 2008, 130, 6099-6113]. Specifically, we
      developed a computational inverse design procedure with the added constraint that
      designed inhibitors bind entirely inside the substrate envelope, a consensus
      volume occupied by natural substrates. The rationale for the substrate-envelope
      constraint is that it prevents designed inhibitors from making interactions
      beyond those required by substrates and thus limits the availability of mutations
      tolerated by substrates but not by designed inhibitors. The strategy resulted in
      subnanomolar inhibitors that bind robustly across a clinically derived panel of
      drug-resistant variants. To further test the substrate-envelope hypothesis, here
      we have designed, synthesized, and assayed derivatives of our original compounds
      that are larger and extend outside the substrate envelope. Our designs resulted
      in pairs of compounds that are very similar to one another, but one respects and
      one violates the substrate envelope. The envelope-respecting inhibitor
      demonstrates robust binding across a panel of drug-resistant protease variants,
      whereas the envelope-violating one binds tightly to wild type but loses affinity
      to at least one variant. This study provides strong support for the substrate
      envelope hypothesis as a design strategy for inhibitors that reduce
      susceptibility to resistance mutations. 

PMID- 23952266
TI  - The effects of stress on periodontal treatment: a longitudinal investigation
      using clinical and biological markers.
AB  - AIM: To investigate the effects of psychosocial stress on the outcome of non
      surgical periodontal treatment (NPT). METHODS: Patients were categorized as
      stressed or unstressed, and the degree of stress was measured. One deep bleeding
      and one deep non-bleeding site >=6 mm were selected in each patient for detailed
      investigation, and the clinical parameters were recorded before and at 6 months
      after NPT. Elastase and C-terminal teleopeptide of type I collagen (ICTP) were
      measured in gingival crevicular fluid (GCF) samples at both intervals. RESULTS:
      The baseline, clinical parameters and biological markers were similar in both
      stressed and unstressed groups, other than for GCF elastase levels, which were
      significantly higher in the stressed group of patients (p < 0.05). The effect of
      stress on the changes for clinical measurements and elastase levels in GCF was
      statistically significant for deep bleeding sites, with the response to treatment
      being poorer in the stressed group. The effects of smoking and the degree of
      stress were not statistically significant for any of the clinical or biological
      parameters (p > 0.05). CONCLUSIONS: Patients under psychosocial stress had a
      poorer outcome following NPT. The assessment of psychosocial stress may be
      valuable in the holistic management of periodontal disease.

PMID- 23952268
TI  - From another perspective.
AB  - No abstract available for this article. 

PMID- 23952269
TI  - The developmental tasks of adolescence and the role of occupational therapy.
AB  - This article is a discussion of the developmental tasks of adolescence, and the
      additional burden disability places on adolescents as they meet the demand of
      those tasks. The role of occupational therapy in the provision of services to
      disabled adolescents is discussed, with recommendations of how to make such
      provision more congruent with the philosophy of occupational therapy. 

PMID- 23952270
TI  - Adolescent development.
AB  - Adolescence is a period of development considered by most to be transitory. It is
      often viewed as filled with storm, rebellion, and conflict. Although the
      profession of occupational therapy has developed special practice areas and
      generated research in the areas of pediatrics and gerontology, little focus in
      our literature has been placed on adolescents and their special needs in
      development and treatment. This paper presents an overview of normal development
      in adolescence. The model of human occupation is used as structure to organize
      research from other fields to provide therapists with useful guidelines for
      treatment. 

PMID- 23952271
TI  - Self-concept/self-esteem development.
AB  - Because the phrases, "has low self-esteem" or "has poor self-concept" are
      frequently used in describing patients, there is a need for a clearer
      understanding of the meaning of these terms. This article explores briefly some
      of the literature on self-concept/self-esteem development through adolescence.
      How deficits in self-esteem can be recognized and utilized in establishing
      treatment goals in occupational therapy is addressed. 

PMID- 23952272
TI  - A home visiting program for adolescents.
AB  - This article describes the origin and evolution of an occupational therapy home
      visiting program for adolescents in Toronto, a large metropolitan area. It
      explains community occupational therapy as it applies to a specific patient
      population, and then gives case examples demonstrating successful intervention. 

PMID- 23952273
TI  - Autistic adolescents.
AB  - Autism is a severely disabling behavioral disorder that impacts upon the
      individual and the family. The current paper (a) discusses the normal
      developmental milestones of adolescence and constrasts them with developmental
      milestones of an autistic adolescent and family. In addition, the current paper
      (b) describes an innovative model program providing specialized services for the
      treatment of autistic adolescents, Community Services for Autistic Adolescents
      and Children (CSAAC), and (c) the role of occupational therapy within the CSAAC
      program is delineated. 

PMID- 23952274
TI  - Head injury in the adolescent years.
AB  - No abstract available for this article. 

PMID- 23952275
TI  - The trauma of spinal cord injury on the adolescent.
AB  - Very simply, a traumatic lesion to the spinal cord results in motor paralysis and
      loss of sensation below the level of the lesion. The previous description omits a
      myriad of serious and related consequences experienced by the spinal cord injury
      (SCI) victim. This injury leaves anyone, young or old, devastated, but especially
      the adolescent who has not yet developed a solid feeling for who he is. The
      injury interrupts not only his physical development, but emotional development as
      well, giving the adolescent few resources to fall back on. Therefore, during his
      hospitalization it is of major importance that the adolescent receive
      rehabilitation services that address not only the common problems of the injury
      and its consequences, but also the adolescent's developmental needs as well. This
      paper deals with the common problems of spinal cord injury which generally are
      intensified in the adolescent and also highlights those aspects of adolescence
      which are especially victimized by such an injury. It also makes some suggestions
      for occupational therapy approaches and programming. 

PMID- 23952276
TI  - The impact of adolescence on the child with cerebral palsy.
AB  - Pre-adolescence is the beginning of self realization that the cerebral palsied
      child will never be "normal." Leading questions and unexplained anger begin
      around the age of nine to eleven years, followed by disbelief, denial and family
      rejection. The occupational therapist may be the first person to whom the child
      or parent reveal their anxieties and hostile feelings. Counseling for self
      esteem, along with an opportunity to meet successful adults who have "survived"
      their cerebral palsy and achieved success in the "real world," can be most
      helpful. Life preparation with both the parents and child should begin at about
      eight years of age (depending upon individual maturation). This kind of joint
      planning avoids many heartaches by anticipating the social rejection of peers and
      unrealistic expectations of "normalcy" by either the parents of the disabled
      child. Treatment goals and career exploration can be directed toward realistic,
      successful achievements. 

PMID- 23952277
TI  - Occupational therapy intervention for the adolescent with juvenile rheumatoid
      arthritis.
AB  - Juvenile Rheumatoid Arthritis (JRA) is a chronic disease capable of producing
      significant physical and psychosocial disabilities. Consequently, the achievement
      of the normal developmental tasks of adolescence is often laborious and delayed
      in the young person with JRA. Literature has documented this delay but has not
      proposed intervention strategies specific to this population. This paper will
      discuss psychosocial and role adjustment problems typical of the adolescent with
      Juvenile Rheumatoid Arthritis, then present treatment strategies to facilitate
      the acquisition of selected developmental tasks as defined by Havighurst. 

PMID- 23952278
TI  - Occupational therapy programming for adolescents with psychosocial dysfunctions.
AB  - The philosophical and structural components of one inpatient adolescent
      psychiatry program in a university center are presented. Set up to address the
      needs of adolescents with severe psychosocial problems, the general design of the
      program is described with particular emphasis on occupational therapy as a very
      active part of the program. The occupational therapy program, its belief systems,
      approaches and specific programming strategies are then presented concluding with
      some thoughts about working with adolescents. 

PMID- 23952280
TI  - From eagle scout to superquad.
AB  - No abstract available for this article. 

PMID- 23952279
TI  - The adolescent life/work planning group.
AB  - Adolescence continues to be a particularly difficult time for the teenager in
      today's society, and for his caring parents and teachers. Few services seem to
      exist specifically for helping adolescents make the transition to adult roles.
      This paper presents issues relevant to the adolescent passage and proposes a
      'wellness' outpatient group in a community health care agency to address the
      particular complex problems of occupational choice/career planning. A new focus
      of care in occupational therapy within the well community is thereby presented. 

PMID- 23952283
TI  - Metamaterials-based label-free nanosensor for conformation and affinity
      biosensing.
AB  - Analysis of molecular interaction and conformational dynamics of biomolecules is
      of paramount importance in understanding their vital functions in complex
      biological systems, disease detection, and new drug development. Plasmonic
      biosensors based upon surface plasmon resonance and localized surface plasmon
      resonance have become the predominant workhorse for detecting accumulated biomass
      caused by molecular binding events. However, unlike surface-enhanced Raman
      spectroscopy (SERS), the plasmonic biosensors indeed are not suitable tools to
      interrogate vibrational signatures of conformational transitions required for
      biomolecules to interact. Here, we show that highly tunable plasmonic
      metamaterials can offer two transducing channels for parallel acquisition of
      optical transmission and sensitive SERS spectra at the biointerface,
      simultaneously probing the conformational states and binding affinity of
      biomolecules, e.g., G-quadruplexes, in different environments. We further
      demonstrate the use of the metamaterials for fingerprinting and detection of the
      arginine-glycine-glycine domain of nucleolin, a cancer biomarker that
      specifically binds to a G-quadruplex, with the picomolar sensitivity. 

PMID- 23952284
TI  - Vesicoscopic bladder neck procedure in children: what we have learned from the
      first series.
AB  - OBJECTIVE: To assess the results of endoscopic bladder neck procedure on the
      anterior bladder wall in children. MATERIALS AND METHODS: Surgery is done in the
      lithotomy position using three 5-mm ports. The bladder is insufflated with CO2. A
      U-shaped incision is made around the bladder neck. A mucosal strip is tabularized
      around a 12 French catheter and covered with the second layer of mucosa. Twenty
      procedures were performed on 18 patients (mean age, 9.8 years), and the follow-up
      period was >1 year (mean, 34 months). Mean operation time was 149 minutes. Twelve
      patients had neurogenic lower urinary tract dysfunction. Fifteen patients failed
      earlier bladder neck surgery, predominantly fascia sling suspension.
      Preoperatively, all patients had low detrusor leak point pressure. Clean
      intermittent catheterization (CIC) was resumed through the urethra in 11 patients
      and through a stoma in 6 patients. RESULTS: Two patients needed conversion
      because of CO2 leakage. Six patients were dry, and 4 improved in the short term
      (3-6 months). After 1 year of follow-up, 2 patients were dry, and 6 improved. In
      the long term, 1 (9%) out of 11 patients who were catheterized through the
      urethra was dry, and 3 of the 11 patients (27%) improved. Of the 6 patients with
      a CIC stoma, 1 (17%) was dry, and 3 (50%) improved. CONCLUSIONS: Endoscopic
      bladder neck surgery is, for most patients, a minor operation, but the long-term
      results are disappointing. The construction of a continent channel for CIC can
      improve the outcome when anterior bladder neck plasty is performed.

PMID- 23952285
TI  - Synthesis of 2-alkenyl- and 2-alkynyl-benzo[b]phospholes by using palladium
      catalyzed cross-coupling reactions.
AB  - Heck, Stille, and Sonogashira reactions of 2-bromobenzo[b]phosphole P-oxide
      afforded a series of 2-alkenyl- and 2-alkynyl-benzo[b]phosphole P-oxides. The
      charge-transfer character of the new benzo[b]phosphole pi-systems in the excited
      state is enhanced by the terminal electron-donating substituents. Furthermore,
      the C-Sn cross-coupling of the bromide was applied to the facile synthesis of a
      new Stille-coupling precursor, 2-stannylbenzo[b]phosphole. 

PMID- 23952286
TI  - Effect of a gestational diabetes management programme on weight after pregnancy.

PMID- 23952287
TI  - Roughness perception in tactile channels: evidence for an opponent process in the
      sense of touch.
AB  - Magnitude estimates of the tactile roughness of raised-dot surfaces revealed that
      perceived overall roughness, defined as the combination of the perceived
      roughness of the dot pattern and the perceived roughness of the individual dots
      in the pattern, is an inverted U-shaped function of dot spacing, reaching a
      maximum at approximately 3.0 mm of dot separation. The hypothesis that Pacinian
      corpuscles are involved in roughness perception has been supported by the finding
      that selective adaptation of the Pacinian corpuscle (PC) channel with a 250-Hz
      stimulus at 20-dB SL results in a decrease in the perceived overall roughness of
      the raised-dot surface at the fingertip. The effect of PC channel adaptation on
      perceived overall roughness was attributable entirely to a reduction in the
      perceived roughness of the individual raised dots; PC adaptation had no effect on
      the perceived roughness of the raised-dot pattern. Selective adaptation of the
      slowly adapting type I (SA I) channel with a 5-Hz stimulus at 20-dB SL had the
      opposite effect of PC channel adaptation and resulted in an increase in the
      perceived roughness of the individual raised dots, and consequently the perceived
      overall roughness of the raised-dot surface. As was the case with PC channel
      adaptation, SA I channel adaptation had no effect on the perceived roughness of
      the pattern. Adaptation with a compound adapting stimulus containing 5- and 250
      Hz components at 20-dB SL had no effect on perceived overall roughness, which
      suggests that the PC and SA I channels operate antagonistically in an opponent
      process fashion in the perception of the microstructure of a textured surface.
      Neither PC adaptation nor SA I adaptation affected perceived pattern roughness,
      which suggests that pattern roughness is coded by relative rather than by
      absolute spatial variation in firing rate.

PMID- 23952288
TI  - Comparative effect of carperitide and furosemide on left atrial pressure in dogs
      with experimentally induced mitral valve regurgitation.
AB  - BACKGROUND: The effects of carperitide on left atrial pressure (LAP) in dogs with
      mitral valve disease (mitral regurgitation, MR) have not been documented.
      OBJECTIVE: The objective was to compare the short-term effects of carperitide
      versus furosemide on LAP and neurohumoral factors in MR dogs. ANIMALS: Six
      healthy Beagle dogs weighing 9.8-12.6 kg (2 males and 4 females; aged 3 years)
      were used. METHODS: Experimental, randomized, cross-over, and interventional
      study. Carperitide 0.1 MUg/kg/min or furosemide 0.17 mg/kg/h (1 mg/kg/6 h) was
      administered to dogs with surgically induced MR for 6 hours, and after a 14 day
      wash-out period, the other drug was administered. LAP, plasma renin activity,
      plasma aldosterone, and echocardiographic variables were measured. RESULTS: Left
      atrial pressure was decreased similarly after the administration of carperitide
      0.1 MUg/kg/min and furosemide 0.17 mg/kg/h (1 mg/kg/6 h) compared with baseline
      in dogs with MR (Baseline 14.75 +/- 3.74 mmHg, carperitide 10.24 +/- 4.97 mmHg, P
      < .01, furosemide 10.77 +/- 5.06 mmHg, P < .05). Plasma renin activity and plasma
      aldosterone were significantly lower after the administration of carperitide than
      after the administration of furosemide (P < .05, respectively). CONCLUSIONS AND
      CLINICAL IMPORTANCE: Carperitide significantly decreased LAP in dogs with acute
      MR caused by experimental chordal rupture. Carperitide can have additional
      benefits from the viewpoint of minimal activation of neurohumoral factors in the
      treatment of dogs with MR. Additional studies in dogs with spontaneous disease
      are warranted.

PMID- 23952289
TI  - Can a high reloading dose of atorvastatin prior to percutaneous coronary
      intervention reduce periprocedural myocardial infarction?
AB  - BACKGROUND: Periprocedural myocardial infarction (MI) is a common complication
      following percutaneous coronary intervention (PCI) and statins have been shown to
      reduce MI in statin-naive patients. We aimed to identify whether a high reloading
      dose of atorvastatin can prevent MI following PCI in patients who were already
      being treated with statins. MATERIAL AND METHODS: In this triple-blind controlled
      randomized clinical trial, 190 candidates for elective PCI, who were already
      using statins and/or other lipid lowering agents such as fibrates, were randomly
      assigned to two equal groups to receive either atorvastatin (80 mg) or placebo
      within 24 hours before the procedure. Serum levels of creatinine kinase
      myocardial isoenzyme (CK-MB), cardiac troponin I (cTNI) and high-sensitive C
      reactive protein (hs-CRP) were measured at baseline and then 6 and 12 hours
      following PCI. Post-procedural MI was defined as troponin elevation>5-fold in
      patients with normal baseline or >20% in those with elevated baseline
      measurements with or without chest pain or ST segment or T wave abnormalities.
      RESULTS: Frequency of MI in the atorvastatin group was 3 (3.1%) vs. 10 (10.5%) in
      the placebo group (p=0.04). The CK-MB rise within 6 hours following PCI was 0.6+/
      0.3 mg/dl in the intervention group versus 3.0+/-1.6 mg/dl in the placebo group.
      Also, the levels of cTNI within 6 and 12 hours in the intervention group was
      significantly lower than the placebo group (p=0.01 and 0.008, respectively). hs
      CRP was significantly lower in the intervention group after 12 hours (p=0.004).
      CONCLUSION: Administration of a high reloading dose of atorvastatin within 24
      hours before PCI could significantly reduce the frequency of periprocedural MI.
      CLINICAL TRIAL REGISTRATION CODE: IRCT201205209768N1.

PMID- 23952290
TI  - Media reporting on suicide: challenges and opportunities.

PMID- 23952291
TI  - The incidence of asymptomatic cerebral microthromboembolism after atrial
      fibrillation ablation: comparison of warfarin and dabigatran.
AB  - BACKGROUND: Cerebral microthromboembolism after atrial fibrillation (AF) ablation
      has been reported in 4-20% with perioperative warfarin. Dabigatran is a new
      anticoagulant in patients with nonvalvular AF. We investigated the incidence of
      asymptomatic cerebral microthromboembolism after AF ablation with perioperative
      warfarin or dabigatran using diffusion-weighted and T2-weighted magnetic
      resonance imaging (MRI). METHODS AND RESULTS: Our study included 210 consecutive
      patients with AF (111 paroxysmal and 99 persistent) who underwent complex
      fractionated atrial electrogram-guided ablation (combined with pulmonary vein
      isolation, n = 110). Catheter irrigation was performed in all cases.
      Uninterrupted warfarin therapy was used in 180 patients (warfarin group) and
      interrupted only on the morning of the procedure with dabigatran in 30
      (dabigatran group). All patients underwent cerebral MRI the day after ablation.
      New microthromboemboli were detected in 10.0% of the warfarin group and 26.7% of
      the dabigatran group (P < 0.05). The incidence of hemopericardium treated with
      pericardiocentesis was lower in the warfarin group than in the dabigatran group
      (2.5% vs 11.1%, P < 0.05). In multivariate analysis, the use of cardioversion was
      a predictor of new microthromboembolism development after AF ablation.
      CONCLUSIONS: The incidence of asymptomatic cerebral microthromboembolism and
      hemopericardium after AF ablation was significantly lower with perioperative
      warfarin therapy than with dabigatran therapy. Dabigatran may not be an effective
      alternative to warfarin for AF ablation, especially in patients who undergo
      cardioversion.

PMID- 23952292
TI  - NQDI 1, an inhibitor of ASK1 attenuates acute ischemic renal injury by modulating
      oxidative stress and cell death.
AB  - Apoptosis signal-regulating kinase 1 (ASK1) is among the signaling events that
      lead to postischemic cell death. Inhibition of ASK1 pathway protected hearts from
      ischemic damage. The present study evaluated the renal protective effects of NQDI
      1, an inhibitor of ASK1, in an animal model of acute ischemic renal failure. Male
      Wistar rats were subjected to right nephrectomy and clamping of left renal
      pedicle for 45 min, or sham operation. The administration of NQDI 1 attenuated
      renal dysfunction and histological changes characteristic for renal
      ischemia/reperfusion injury (IRI). Apoptosis of renal tissues, as detected by
      TUNEL staining, was also reduced together with p53 protein expression, and renal
      levels of MDA and SOD with NQDI 1 administration and BCL2 was up regulated. In
      conclusion, inhibition of ASK1 is of therapeutic potential against acute ischemic
      renal injury. Its protective effects are mediated via inhibition of apoptosis and
      oxidative stress. 

PMID- 23952293
TI  - Gold-catalyzed hydration of haloalkynes to alpha-halomethyl ketones.
AB  - A general atom-economical approach for the synthesis of alpha-halomethyl ketones
      is demonstrated through hydration of a wide range of haloalkynes. Other
      outstanding features include excellent yields from both alkyl- and aryl
      substituted haloalkynes and wide functional group tolerance. This protocol is an
      alternative to conventional alpha-halogenation of ketones. 

PMID- 23952294
TI  - Ruthenium(II) and osmium(II) complexes bearing bipyridine and the N-heterocyclic
      carbene-based C^N^C pincer ligand: an experimental and density functional theory
      study.
AB  - Ruthenium(II) and osmium(II) complexes [M(C^N^C)(N^N)L](n+) (L = Cl(-), n = 1; L
      = CH3CN, t-BuNC, n = 2) containing a neutral tridentate N-heterocyclic carbene
      (NHC)-based pincer ligand, either 2,6-bis(1-butylimidazol-2-ylidene)pyridine
      (C(1)^N^C(1)) or 2,6-bis(3-butylbenzimidazol-2-ylidene)pyridine (C(2)^N^C(2)),
      and a neutral 2,2'-bipyridine-type aromatic diimine have been prepared.
      Investigations into the effects of varying M (Ru and Os), C^N^C, N^N, and L on
      the structural, electrochemical, absorption, and emission characteristics
      associated with [M(C^N^C)(N^N)L](n+) are presented. Interestingly, spectroscopic
      findings and time-dependent density functional theory (TD-DFT) calculations in
      this work support a dpi(Ru(II)/Os(II)) -> pi*(N^N) metal-to-ligand charge
      transfer (MLCT) assignment for the lowest-energy transition in
      [M(C^N^C)(N^N)L](n+) and not a dpi(Ru(II)/Os(II)) -> pi*(C^N^C) MLCT assignment.
      This is in stark contrast to [Ru(tpy)(bpy)Cl](+) and [Os(tpy)(bpy)Cl](+) (tpy =
      2,2':6',2"-terpyridine, bpy = 2,2'-bipyridine) for which the lowest-energy
      transitions are assigned as dpi(Ru/Os) -> pi*(tpy) MLCT transitions.
      [Ru(II)(C^N^C)(N^N)L](n+) is emissive with emission maxima of around 600-700 nm
      observed upon photoexcitation of their dpi(Ru(II)) -> pi*(N^N) MLCT bands. The
      electronic structures for [Ru(C^N^C)(N^N)Cl](0) have also been probed by
      spectroelectrochemistry, electron paramagnetic resonance (EPR) spectroscopy, and
      DFT calculations, which reveal that the lowest unoccupied molecular orbitals
      (LUMOs) for [Ru(C^N^C)(N^N)Cl](+) are N^N-based. 

PMID- 23952295
TI  - Analysis of the influence of a metha-type metaphysical stem on biomechanical
      parameters.
AB  - The full postoperative loading of the limb is possible if patients are properly
      selected and qualified for hip arthroplasty and the requirements as to the proper
      position of the metaphysial stem are met. The lack of precision, and patient
      qualification which does not satisfy the fixed criteria may result in stem
      setting inconsistent with the assumptions. An analysis based on the finite
      element method (FEM) will enable one to find out how to plan the magnitude of
      operated joint loading on the basis of the position of the stem in the
      postoperative radiograph. By analyzing the distribution of bone tissue
      deformations one can identify the zones where the spongy bone is overloaded and
      determine the strain level in comparison with the one determined for a model of
      the bone with the stem in proper position. On the basis of the results obtained
      one can estimate the range of loads for the operated limb, which will not result
      in the loss of the stem's primary stability prior to obtaining secondary
      stability through osteointegration. Moreover, an analysis of the formation of
      bone structures around the stem showed that the incorrect setting of a Metha-type
      stem may lead to the initiation of loosening. 

PMID- 23952296
TI  - Paediatric rhinitis: position paper of the European Academy of Allergy and
      Clinical Immunology.
AB  - Rhinitis is a common problem in childhood and adolescence and impacts negatively
      on physical, social and psychological well-being. This position paper, prepared
      by the European Academy of Allergy and Clinical Immunology Taskforce on Rhinitis
      in Children, aims to provide evidence-based recommendations for the diagnosis and
      therapy of paediatric rhinitis. Rhinitis is characterized by at least two nasal
      symptoms: rhinorrhoea, blockage, sneezing or itching. It is classified as
      allergic rhinitis, infectious rhinitis and nonallergic, noninfectious rhinitis.
      Similar symptoms may occur with other conditions such as adenoidal hypertrophy,
      septal deviation and nasal polyps. Examination by anterior rhinoscopy and allergy
      tests may help to substantiate a diagnosis of allergic rhinitis. Avoidance of
      relevant allergens may be helpful for allergic rhinitis (AR). Oral and intranasal
      antihistamines and nasal corticosteroids are both appropriate for first-line AR
      treatment although the latter are more effective. Once-daily forms of
      corticosteroids are preferred given their improved safety profile. Potentially
      useful add-on therapies for AR include oral leukotriene receptor antagonists,
      short bursts of a nasal decongestant, saline douches and nasal anticholinergics.
      Allergen-specific immunotherapy is helpful in IgE-mediated AR and may prevent the
      progression of allergic disease. There are still a number of areas that need to
      be clarified in the management of rhinitis in children and adolescents. 

PMID- 23952297
TI  - HIV and Schistosoma haematobium prevalences correlate in sub-Saharan Africa.
AB  - OBJECTIVE: Epidemiological studies have observed that genital schistosomiasis
      increases the risk of HIV infection in Africa. We analysed the correlation
      between Schistosoma haematobium prevalence and HIV prevalence across sub-Saharan
      African countries. DESIGN: Regression analysis of prevalence of HIV and S.
      haematobium across sub-Saharan African countries. METHODS: Using compiled country
      level S. haematobium prevalence, HIV prevalence and other demographic and
      economic data from published sources, we applied univariate and multivariate
      regression models to assess the correlations between S. haematobium prevalence
      and HIV prevalence while controlling for risk factors associated with each
      infection. RESULTS: In 43 sub-Saharan African countries, the mean prevalence of
      S. haematobium was 22.4% [standard deviation (SD): 9.8%] and for HIV was 6.21%
      (SD: 5.71%). In multivariate analysis, adjusted for prevalence of male
      circumcision, years since a country's first HIV/AIDS diagnosis, geographical
      region and immunization coverage, each S. haematobium infection per 100
      individuals was associated with a 2.9% (95% CI: 0.2-5.8%) relative increase in
      HIV prevalence. S. haematobium was not associated with Schistosoma mansoni, HSV
      2, hepatitis C, malaria or syphilis. CONCLUSIONS: Schistosoma haematobium
      prevalence was associated with HIV prevalence in sub-Saharan Africa. Controlling
      S. haematobium may be an effective means of reducing HIV transmission in sub
      Saharan Africa.

PMID- 23952299
TI  - Insights into the pharmacological targeting of the trigeminocervical complex in
      the context of treatments of migraine.
AB  - Migraine is one of the most severe and debilitating brain disorders. Most
      scientists accept that it involves activation and sensitization of the
      trigeminovascular system, which includes the sensory peripheral projections to
      the pain-producing dura mater, and a central projection to the trigeminal nucleus
      caudalis and its cervical extension, the trigeminocervical complex (TCC). The
      development of the anti-migraine therapeutics, triptans-5-HT1B/1D receptor
      agonists, had originally targeted the craniovasculature to exert therapeutic
      effects, and this locus of action seemed to predict efficacy in the clinic.
      However, subsequent development of novel targets, using the same strategy failed
      to replicate this early success and as a consequence central mechanisms of action
      away from the dural vasculature were thought to be responsible for these
      therapeutic effects. Coupled to this, migraine has been hypothesized to involve a
      dysfunction of areas of the brainstem and diencephalon, which seem to mediate the
      activation, or perception of activation, of the trigeminovascular system as well
      as sensitization of neuronal pathways that drive trigeminovascular activation.
      Therefore, drug targets that act in the brain, specifically on the central
      component of the trigeminovascular system, the TCC, would seem to be ideally
      placed to modulate this nociceptive pathway and relieve migraine, but
      particularly the headache phase. This review will discuss how the TCC, rather
      than other more craniovascular sites, may be the anatomical target of some of the
      current and emerging therapies to relieve migraine symptoms, and why this should
      prove to be a fruitful area for drug development for the treatment of migraine. 

PMID- 23952298
TI  - On the importance of balancing selection in plants.
AB  - Balancing selection refers to a variety of selective regimes that maintain
      advantageous genetic diversity within populations. We review the history of the
      ideas regarding the types of selection that maintain such polymorphism in
      flowering plants, notably heterozygote advantage, negative frequency-dependent
      selection, and spatial heterogeneity. One shared feature of these mechanisms is
      that whether an allele is beneficial or detrimental is conditional on its
      frequency in the population. We highlight examples of balancing selection on a
      variety of discrete traits. These include the well-referenced case of self
      incompatibility and recent evidence from species with nuclear-cytoplasmic
      gynodioecy, both of which exhibit trans-specific polymorphism, a hallmark of
      balancing selection. We also discuss and give examples of how spatial
      heterogeneity in particular, which is often thought unlikely to allow protected
      polymorphism, can maintain genetic variation in plants (which are rooted in
      place) as a result of microhabitat selection. Lastly, we discuss limitations of
      the protected polymorphism concept for quantitative traits, where selection can
      inflate the genetic variance without maintaining specific alleles indefinitely.
      We conclude that while discrete-morph variation provides the most unambiguous
      cases of protected polymorphism, they represent only a fraction of the balancing
      selection at work in plants.

PMID- 23952300
TI  - A prenatal origin of childhood essential thrombocythaemia.

PMID- 23952301
TI  - Effect of gamma radiation on Phenoloxidase pathway, antioxidant defense mechanism
      in Helicoverpa armigera (Lepidoptera: Noctuidae) and its implication in inherited
      sterility towards pest suppression.
AB  - PURPOSE: To investigate age-correlated radiosensitivity in highly radioresistant
      lepidopteran pest, Helicoverpa armigera, upon exposure to ionizing radiation and
      to examine the irradiation impact on stress-molecular responses in F1 (first
      filial) progeny of irradiated (100 Gy) male moths in relation to its reproductive
      behavior. MATERIALS AND METHODS: Efficacy of sub-lethal gamma radiation was
      evaluated on two markedly apart ontogenic stages, neonates and adult moths.
      Differential growth, reproductive behavior and stress-indicating molecular
      responses were examined upto F1 progeny of sub-sterilized moths. Free-radical
      scavenging enzymes, superoxide dismutase (SOD), catalase (CAT) and Phenoloxidase
      cascade enzymes, pro-phenoloxidase (PPO), its activating enzyme (PPAE) were
      studied in irradiated and irradiated plus microbial challenge regimen (dual
      stress) by Real-time RT-PCR (reverse-transcription-polymerase-chain-reaction).
      RESULTS: An inverse correlation of radiosensitivity with developmental age of
      insect was observed. F1 sterility was higher than parent sterility. F1 progeny
      exhibited protraction in development and decreased survival upon irradiation. Sex
      ratio in F1 progeny was skewed towards males. PPO, PPAE, SOD and CAT transcripts
      were downregulated upon neonate irradiation resulting in enhanced vulnerability
      of larvae to incidental microbial challenge. These transcripts were upregulated
      in F1 progeny of sub-sterilized male moths (100 Gy) upon dual-stress.
      CONCLUSIONS: Irradiation impact on stress-indicating molecular responses in F1
      progeny is correlated with its reproductive performance. These observations will
      permit defining regimen having pragmatic viability of 'F1 sterility technique'
      for pest suppression. Gamma dose of 100 Gy would ensure balance between induced
      sterility of males and their field competitiveness. These parameters would
      facilitate integration of biocontrol strategy with parabiological 'Sterile Insect
      Release Technique'.

PMID- 23952302
TI  - B?B and B=E (E = N and o) multiple bonds in the coordination sphere of late
      transition metals.
AB  - Because of their unusual structural and bonding motifs, multiply bonded boron
      compounds are fundamentally important to chemists, leading to enormous research
      interest. To access these compounds, researchers have introduced sterically
      demanding ligands that provide kinetic as well as electronic stability. A
      conceptually different approach to the synthesis of such compounds involves the
      use of an electron-rich, coordinatively unsaturated transition metal fragment. To
      isolate the plethora of borane, boryl, and borylene complexes, chemists have also
      used the coordination sphere of transition metals to stabilize reactive motifs in
      these molecules. In this Account, we summarize our results showing that
      increasingly synthetically challenging targets such as iminoboryl (B=N), oxoboryl
      (B=O), and diborene (B?B) fragments can be stabilized in the coordination sphere
      of late transition metals. This journey began with the isolation of two new
      iminoboryl ligands trans-[(Cy3P)2(Br)M(B=N(SiMe3))] (M = Pd, Pt) attached to
      palladium and platinum fragments. The synthesis involved oxidative addition of
      the B-Br bond in (Me3Si)2N?BBr2 to [M(PCy3)2] (M = Pt, Pd) and the subsequent
      elimination of Me3SiBr at room temperature. Variation of the metal, the metal
      bound coligands, and the substituent at the nitrogen atom afforded a series of
      analogous iminoboryl complexes. Following the same synthetic strategy, we also
      synthesized the first oxoboryl complex trans-[(Cy3P)2BrPt(BO)]. The labile
      bromide ligand adjacent to platinum makes the complex a viable candidate for
      further substitution reactions, which led to a number of new oxoboryl complexes.
      In addition to allowing us to isolate these fundamental compounds, the synthetic
      strategy is very convenient and minimizes byproducts. We also discuss the
      reaction chemistry of these types of compounds. In addition to facilitating the
      isolation of compounds with B=E (E = N, O) triple bonds, the platinum fragment
      can also stabilize a diborene (RB?BR) moiety, a bonding motif that thus far had
      only been accessible when stabilized by N-heterocyclic carbenes (NHCs). In the
      new pi-diborene [(Et3P)2Pt(B2Dur2)] (Dur = 2,3,5,6-Me4-C6H) complex, the diborene
      ligand receives electron density from Pt, leading to a strong Pt-B bond and a B?B
      bond. We attribute this result to the very short B?B bond distance (1.51(2) A)
      while coordinated to platinum. Overall, an increasing number of chemists are
      examining the chemistry of multiply bound boron compounds. The isolation of an
      oxoboryl complex is of special interest not only from a structural standpoint but
      also because of its orbital similarities to the ubiquitous CO ligand. Detailed
      computational studies of the pi-diborene complex [(Et3P)2Pt(B2Dur2)] show that
      the bonding properties of this molecule violate the widely accepted Dewar-Chatt
      Duncanson (DCD) bonding model. 

PMID- 23952303
TI  - Nitric oxide production, systemic inflammation and lipid metabolism in
      periodontitis patients: possible gender aspect.
AB  - AIM: Nitric oxide (NO) plays a crucial role in vascular tone regulation and is
      involved in pathogenesis of periodontitis. In this cross-sectional study, we
      investigated the serum and saliva levels of NO metabolites in periodontal disease
      and their relationship with serum C-reactive protein (CRP) levels, lipids
      metabolism and periodontal disease severity. MATERIAL AND METHODS: Serum and
      saliva were collected from non-smoking patients with generalized severe
      periodontitis (n = 89) and healthy controls (n = 56). Serum and salivary levels
      of NO metabolites, serum levels of high density lipoproteins (HDL), low density
      lipoproteins (LDL), triglycerides, cholesterol and CRP were measured. Data were
      analysed in whole population and in different gender groups. RESULTS:
      Periodontitis patients exhibited significantly lower serum and saliva levels of
      NO metabolites and significantly higher LDL, cholesterol and CRP levels than
      control group. Similar findings were observed within male but not within female
      population. Serum NO metabolites levels exhibited significant negative
      correlation with CRP in whole population and in male population. Significant
      positive correlation of serum NO metabolite levels with HDL levels was observed
      in whole population. CONCLUSION: NO production is reduced in periodontitis,
      especially in male population. Gender might be an important factor in assessing
      risk of cardiovascular disease in periodontitis.

PMID- 23952304
TI  - Restricted gene flow within and between rapidly diverging Neotropical plant
      species.
AB  - Speciation involves the evolution of traits and genetic differences that
      contribute to reproductive isolation and the cessation of gene flow, and studying
      closely related species and divergent populations gives insight into how these
      phenomena proceed. Here, we document patterns of gene flow within and between two
      members of a rapid Neotropical species radiation, Costus pulverulentus and Costus
      scaber (Costaceae). These species co-occur in the tropical rainforest and share
      pollinators, but are reproductively isolated by a series of prezygotic barriers,
      some of which show evidence of reinforcement at sympatric sites. Here, we
      genotype microsatellite markers in plants from eight sites that span the
      geographical range of both species, including four sympatric sites. We also
      genotype putative hybrids found at two sympatric sites. We find high levels of
      genetic isolation among populations within each species and low but detectable
      levels of introgression between species at sympatric sites. Putative hybrids
      identified by morphology are consistent with F1 or more advanced hybrids. Our
      results highlight the effectiveness of prezygotic isolating mechanisms at
      maintaining species boundaries in young radiations and provide empirical data on
      levels of gene flow consistent with reinforcement. 

PMID- 23952305
TI  - From the editor's desk.
AB  - No abstract available for this article. 

PMID- 23952306
TI  - From another perspective.
AB  - No abstract available for this article. 

PMID- 23952307
TI  - Work-related programming in occupational therapy.
AB  - This paper presents an examination of the historical evolution of work-related
      theory in occupational therapy as it paralleled environmental influences (social,
      political, technical) and how that has affected the thrust and position of the
      profession today. 

PMID- 23952308
TI  - Vocational evaluation in the private sector.
AB  - There is a resurgence of interest in vocational rehabilitation among occupational
      therapists as evidenced by the number of vocational evaluation programs which
      have been established in recent years using various models of practice. This
      paper will describe the process for practice in a private, free-standing facility
      in which occupational therapists provide a variety of work related services. The
      focus will be on evaluation which is the primary service and usually servces as
      the keystone to subsequent courses of action. 

PMID- 23952309
TI  - The unique role of occupational therapy in industry.
AB  - Experienced occupational therapists have five particular characteristics gained
      from their education and clinical experience which make them uniquely suited for
      a major role in rehabilitation of persons with industrial injuries. These are:
      (1) knowledge of injury and illness, (2) understanding of psych-social aspects of
      disability, (3) knowledge of the rehabilitation system, (4) ability to analyze
      tasks and (5) ability to creatively adapt the physical environment. Skills in
      administration, teaching and the ability to deal with a variety of people from
      different backgrounds: educational, socio-economic and work ethic are also
      vitally important for effective functioning in and with industry. For the
      aspirant, the beginning steps are to become familiar with the tasks workers
      perform, to self management personnel on a rehabilitation philosophy by showing
      them how return on investment can be realized, and to inform supervisors, union
      officials and employees of the goals of such ideas and how they will work in
      their company. This paper will describe how one occupational therapist has
      developed a program and functioned successfully in and with the railroad
      industry. Analysis of statistics and a case study will show cost savings and
      return on energy and on initial investment. The historical link between
      occupational therapy and industry gives credence to the unique contribution of
      occupational therapy and establishes the need for more occupational therapists in
      industry. 

PMID- 23952310
TI  - Work center.
AB  - Changing one's role from student to worker is often a difficult transition,
      especially today when options for employment are linked with specialized
      training. For the handicapped adolescent it is almost impossible without very
      special training and guidance. Recent legislation affecting the handicapped
      mandated that efforts to assist this process shall begin two years prior to the
      student's graduation or at age twenty. Some writers insist that such supportive
      programming should begin when students are quite young and that it should be
      conducted within realistic "work" environments. Recognizing this need, the
      occupational therapy staff in a private school for special needs children and
      adolescents have taken a proactive stance and have initiated a work program for
      all students beginning as early as age 10. This paper describes the pilot Work
      Center, organized within a school and structured on a rehabilitation workshop
      model. 

PMID- 23952311
TI  - A private practice work evaluation unit.
AB  - A private practice, free standing work evaluation center was established in
      November 1982 to serve a large metropolitan area in northern California.
      Originally conceived to evaluate and treat persons with traumatic hand and/or
      upper extremity injuries, the practice has now expanded to include services for
      industrially injured workers, persons with personal injury claims who have
      sustained a broad range of physical and/or emotional disabilities, as well as
      individuals receiving State rehabilitation services. The role of the occupational
      therapist within this vocationally oriented unit is varied and has proven highly
      beneficial for individuals with various kinds of disabilities. While occupational
      therapists have moved in and out of this area of practice over the years, they
      now seem to be re-establishing themselves as viable and significant parts of work
      related programming. Their unique skills and broad expertise enhance overall care
      of impaired workers and 'bridge the gap' between medical and vocational services.
      This paper presents a brief description of programming in a work unit and
      concludes with recommendations for others interested in this area of practice. 

PMID- 23952312
TI  - The Occupational Therapist's Role in Employee Health Promotion Programs.
AB  - The first challenge in developing an effective health promotion program for
      employees is the performance of a health needs assessment on the target
      population. In an effort to meet this challenge, 600 corporate employees were
      surveyed and compared with respect to the allotment of time to work, leisure, and
      self/family care activities; health risk factors; perceived health; and activity
      satisfaction. The results of the study indicated that the employees participating
      in the corporate health and fitness programs were not the high risk individuals
      who consume the majority of the corporate medical dollar. The role of the
      occupational therapist in meeting the needs of high risk employees is discussed.
      A brief review of the literature addresses research efforts in the area of health
      promotion in industry and the role of the occupational therapist in disease
      prevention. The appropriateness of occupational therapy education, training and
      theory in relation to health promotion programs and the utilization of the five
      occupational performance components in the evaluation of employee populations is
      outlined. Finally, the role of the occupational therapist working in specific
      areas of health promotion is reviewed, including: back pain reduction, substance
      abuse treatment, cardiac fitness/rehabilitation and hypertension control, smoking
      cessation, weight reduction, stress management, industrial accident and injury
      prevention, and self-responsibility for health instruction. 

PMID- 23952313
TI  - The expanding role of occupational therapy in the treatment of industrial hand
      injuries.
AB  - A recent survey of members of the American Society of Hand Therapists revealed an
      expanding role for the therapist in the treatment of industrial hand injuries. In
      the traditional role of treatment provider, occupational therapists are using
      their assessment tools and work capacity programming to aid in predicting return
      to work readiness. This is aimed at preventing reinjury of the present patient
      population. In addition to this, therapists have begun to identify relationships
      between specific injuries and work that produced them. This gives rise to a
      specified goal of preventing the injury from ever occuring. To reach this goal
      therapists are becoming involved in industrial settings and are working with
      industrial safety teams. 

PMID- 23952314
TI  - Occupational therapy leadership potential can be developed through marketing
      techniques.
AB  - No abstract available for this article. 

PMID- 23952315
TI  - Time management in clinical practice.
AB  - Organizing one's time to accomplish the tasks that bombard an occupational
      therapist each day is imperative to personal and professional survival.
      Clinicians have more and greater responsibility than ever before, but are not
      able to quantitatively increase the number of clock hours to handle the increased
      workload. The answer lies in managing one's allocated time more effectively.
      Clinicians tend to fall into the same "time traps" as everyone else. They can
      waste time by not concentrating on one task at a time, or through
      procrastination. It is not unusual for a clinician to attempt to see as many
      patients as possible without a clear system of priority setting. This article
      outlines ways of applying time management principles to the unique demands of
      clinical practice. Specific methods of increasing a clinician's time management
      skills are presented through the Clinical Time Log, the System of Clinical
      Prioritization, applications of Pareto's Rule, and specific suggestions for
      better time management in clinical practice. 

PMID- 23952316
TI  - Program evaluation research.
AB  - Program evaluation research should be viewed as an essential administrative tool.
      It can provide data needed by occupational therapy managers for assessing the
      effectiveness and efficiency of services and operations. This article will
      provide an overview of the purposes, types, basic steps, potential problems, and
      benefits of program evaluation. 

PMID- 23952317
TI  - Something new and useful.
AB  - No abstract available for this article. 

PMID- 23952319
TI  - Antimicrobial effect of natural polyphenols with or without antibiotics on
      Chlamydia pneumoniae infection in vitro.
AB  - Chlamydia pneumoniae is a human pathogen that causes multiple diseases worldwide.
      Despite appropriate therapy with antichlamydial antibiotics, chronic exacerbated
      diseases often occur and lead to serious sequelae. The use of the macrolide
      clarithromycin and the fluoroquinolone ofloxacin has improved the treatment of
      chlamydial infection, but therapy failure is still a major problem. In this work,
      we studied the pretreatment with natural polyphenols and subsequent treatment
      with clarithromycin or ofloxacin. The phenolic compounds resveratrol and
      quercetin improved the antichlamydial effect of clarithromycin and ofloxacin. In
      particular, resveratrol at 40 MUM and quercetin at 20 MUM exhibited significant
      growth inhibition on C. pneumoniae in presence of clarithromycin or ofloxacin
      compared to controls. In addition, we demonstrated that both resveratrol and
      quercetin decreased IL-17 and IL-23 production in a time-dependent manner in C.
      pneumoniae-infected cells. The results showed a particularly strong inhibition of
      the IL-23 levels released with combined treatment of resveratrol or quercetin and
      ofloxacin or clarithromycin, suggesting that the combined treatment may afford a
      synergistic effect in controlling Chlamydia infections.

PMID- 23952320
TI  - Tetrabutylammonium 2-pyridyltriolborate salts for Suzuki-Miyaura cross-coupling
      reactions with aryl chlorides.
AB  - Palladium-catalyzed Suzuki-Miyaura cross-coupling reactions of tetrabutylammonium
      2-pyridyltriolborate salts with various aryl (heteroaryl) chlorides can produce
      the corresponding desired coupling products with good to excellent yields. These
      tetrabutylammonium salts are more reactive than the corresponding lithium salts.
      The coupling reactions with aryl chlorides progressed in the presence of
      PdCl2dcpp (3 mol %) and CuI/MeNHCH2CH2OH (20 mol %) in anhydrous DMF without
      bases. 

PMID- 23952321
TI  - Complex regional pain syndrome following lateral lumbar interbody fusion: case
      report.
AB  - The minimally destructive lateral transpsoas approach to the spine has been used
      in the treatment of various lumbar spinal pathologies. Approach-specific
      complications have been reported due to the unique surgical corridor and lateral
      anatomical structures. The authors report a case of complex regional pain
      syndrome (CRPS) following interbody cage placement utilizing the lateral lumbar
      transpsoas approach. A review of the literature is discussed. Further
      clarification of the mechanism of CRPS and its treatments remains crucial for the
      fine-tuning of novel surgical techniques and complication avoidance during the
      development of these techniques. 

PMID- 23952322
TI  - The use of cooled saline during bone drilling to reduce the incidence of upper
      limb palsy after cervical laminoplasty: clinical article.
AB  - OBJECT: No previous hypothesis has attempted to fully account for the occurrence
      of upper-limb palsy (ULP) after cervical laminoplasty. The authors propose that
      friction-generated heat from a high-speed drill may cause thermal injury to the
      nerve roots close to the drilled bone, which may then lead to ULP. The authors
      investigated the effect of cooling the saline used for irrigation during the
      drilling on the incidence of upper-limb (C-5) palsy following cervical
      laminoplasty. METHODS: The irrigation saline for drilling was used at room
      temperature (RT, average temperature of 25.6 degrees C) in operations of 79
      patients (the RT group) and cooled to an average of 12.1 degrees C in operations
      of 80 patients (the low-temperature [LT] group). The authors used a hand-held
      dynamometer to precisely assess muscle strength presurgery and 2 weeks
      postsurgery. RESULTS: There was a 7.6% and 1.9% decrease in the strength of the
      deltoid muscle, a 10.1% and 4.4% decrease in the strength of the biceps brachii,
      a 1.3% and 0.6% decrease in the strength of the triceps brachii, and a 7.6% and
      3.1% decrease in grip strength in the RT and LT groups, respectively.
      Multivariate analysis revealed that a significant predictor for decreased deltoid
      muscle strength was the use of irrigation saline at RT. CONCLUSIONS: Using cooled
      irrigation saline during bone drilling significantly decreased the incidence of
      ULP and can thus be recommended as a simple method for the prevention of ULP.

PMID- 23952323
TI  - A novel 3D guidance system using augmented reality for percutaneous
      vertebroplasty: technical note.
AB  - Augmented reality (AR) is an imaging technology by which virtual objects are
      overlaid onto images of real objects captured in real time by a tracking camera.
      This study aimed to introduce a novel AR guidance system called virtual
      protractor with augmented reality (VIPAR) to visualize a needle trajectory in 3D
      space during percutaneous vertebroplasty (PVP). The AR system used for this study
      comprised a head-mount display (HMD) with a tracking camera and a marker sheet.
      An augmented scene was created by overlaying the preoperatively generated needle
      trajectory path onto a marker detected on the patient using AR software, thereby
      providing the surgeon with augmented views in real time through the HMD. The
      accuracy of the system was evaluated by using a computer-generated simulation
      model in a spine phantom and also evaluated clinically in 5 patients. In the 40
      spine phantom trials, the error of the insertion angle (EIA), defined as the
      difference between the attempted angle and the insertion angle, was evaluated
      using 3D CT scanning. Computed tomography analysis of the 40 spine phantom trials
      showed that the EIA in the axial plane significantly improved when VIPAR was used
      compared with when it was not used (0.96 degrees  +/- 0.61 degrees  vs 4.34
      degrees  +/- 2.36 degrees , respectively). The same held true for EIA in the
      sagittal plane (0.61 degrees  +/- 0.70 degrees  vs 2.55 degrees  +/- 1.93 degrees
      , respectively). In the clinical evaluation of the AR system, 5 patients with
      osteoporotic vertebral fractures underwent VIPAR-guided PVP from October 2011 to
      May 2012. The postoperative EIA was evaluated using CT. The clinical results of
      the 5 patients showed that the EIA in all 10 needle insertions was 2.09 degrees 
      +/- 1.3 degrees  in the axial plane and 1.98 degrees  +/- 1.8 degrees  in the
      sagittal plane. There was no pedicle breach or leakage of polymethylmethacrylate.
      VIPAR was successfully used to assist in needle insertion during PVP by providing
      the surgeon with an ideal insertion point and needle trajectory through the HMD.
      The findings indicate that AR guidance technology can become a useful assistive
      device during spine surgeries requiring percutaneous procedures. 

PMID- 23952324
TI  - Desmoplastic fibroma of the spine causing severe mediastinal compression and
      brachial plexus encasement: report of 2 cases.
AB  - Desmoplastic fibroma (DF) is a rare bone tumor that accounts for about 0.1%-0.3%
      of all bone tumors. It is typically characterized as slow growing, but in rare
      cases it can proliferate extensively and exhibit locally aggressive
      characteristics. It is found most commonly in the appendicular skeleton and
      rarely in the axial skeleton. The authors present the cases of 2 women in their
      20s with DF originating from the cervicothoracic spine. Both tumors intimately
      involved the brachial plexus and caused significant impingement of the
      mediastinum resulting in cardiopulmonary compromise. Both patients underwent
      hemiclamshell thoracotomies for tumor resection, and in both cases subtotal
      resection was performed given the encasement of the brachial plexus. Although DF
      is a benign process, it can be locally aggressive and proliferate at extensive
      rates. The authors describe these 2 cases, review the literature, and discuss
      management. 

PMID- 23952325
TI  - The pathophysiology of venous hypertensive myelopathy--study of an animal model:
      laboratory investigation.
AB  - OBJECT: The authors undertook this study to establish an animal model to
      investigate the pathophysiological changes of venous hypertensive myelopathy
      (VHM). METHODS: This study was a randomized control animal study with blinded
      evaluation. The VHM model was developed in 24 adult New Zealand white rabbits by
      means of renal artery and vein anastomosis and trapping of the posterior vena
      cava; 12 rabbits were subjected to sham surgery. The rabbits were investigated by
      spinal function evaluation, abdominal aortic angiography, spinal MRI, and
      pathological examination of the spinal cord at different follow-up stages.
      RESULTS: Twenty-two (91.67%) of 24 model rabbits survived the surgery and
      postoperative period. The patency rate of the arteriovenous fistula was 95.45% in
      these 22 animals. The model rabbits had significantly decreased motor and sensory
      hindlimb function as well as abnormalities at the corresponding segments of the
      spinal cord. Pathological examination showed dilation and hyalinization of the
      small blood vessels, perivascular and intraparenchymal lymphocyte infiltration,
      proliferation of glial cells, and neuronal degeneration. Electron microscopic
      examination showed loose lamellar structure of the myelin sheath, increased
      numbers of mitochondria in the thin myelinated fibers, and pyknotic neurons.
      CONCLUSIONS: This model of VHM is stable and repeatable. Exploration of the
      sequential changes in spinal cord and blood vessels has provided improved
      understanding of this pathology, and the model may have potential for improving
      therapeutic results.

PMID- 23952327
TI  - Urinary biomarkers for acute kidney injury in dogs.
AB  - Routinely, kidney dysfunction and decreased glomerular filtration rate (GFR) are
      diagnosed by the evaluation of changes in the serum creatinine (SCr) and blood
      urea nitrogen (BUN) concentrations. However, neither of these tests is sensitive
      or specific enough for the early diagnosis of impaired kidney function because
      they are both affected by other renal and nonrenal factors. Furthermore, kidney
      injury can be present in the absence of kidney dysfunction. Renal reserve enables
      normal GFR even when nephrons are damaged. Renal biomarkers, especially those
      present in urine, may be useful for the study of both acute and chronic
      nephropathies. The aim of this review is to describe the current status of
      urinary biomarkers as diagnostic tools for kidney injury in dogs with particular
      focus on acute kidney injury (AKI). The International Renal Interest Society
      (IRIS) canine AKI grading system and the implementation of urinary biomarkers in
      this system also are discussed. The discovery of novel urinary biomarkers has
      emerged from hypotheses about the pathophysiology of kidney injury, but few
      proteomic urine screening approaches have been described in dogs. Lack of
      standardization of biomarker assays further complicates the comparison of novel
      canine urinary biomarker validation results among studies. Future research should
      focus on novel biomarkers of renal origin and evaluate promising biomarkers in
      different clinical conditions. Validation of selected urinary biomarkers in the
      diagnosis of canine kidney diseases must include dogs with both renal and
      nonrenal diseases to evaluate their sensitivity, specificity as well as their
      negative and positive predictive values. 

PMID- 23952328
TI  - Increasing awareness of hypoglycaemia in patients with type 2 diabetes treated
      with oral agents.
AB  - Hypoglycaemia is the most common acute complication of type 2 diabetes and can
      limit therapeutic efforts to improve glycaemic control in order to protect
      against long-term complications. It is a potential side effect of the drugs used
      to treat diabetes, specifically exogenous insulin or insulin secretagogues. As
      many people are prescribed these agents, hypoglycaemia is frequent in clinical
      practice, although patients commonly do not inform their healthcare professional
      of the problems spontaneously. The impact of hypoglycaemia on the patient and to
      the healthcare system is significant through reduced treatment satisfaction and
      adherence, reduced quality of life and serious health consequences. This has
      financial implications and costs for the patient, the public and the economy at
      large. The single most important risk factor for hypoglycaemia is previous
      hypoglycaemia. Prevention depends on appropriate education regarding diabetes
      management and selfcare, self-monitoring of blood glucose, awareness of factors
      that may precipitate hypoglycaemia, and an individualized approach to therapy and
      glycaemic control targets. The purpose of this review is to increase
      understanding of the impact and consequences of hypoglycaemia, in particular that
      associated with sulphonylurea therapy, and to highlight areas requiring more
      attention in order to improve the overall management of people with type 2
      diabetes.

PMID- 23952329
TI  - Treatment resistance in people with chronic mental disorders--core clinical
      issues, social inclusion and getting the balance right.

PMID- 23952330
TI  - DurataTM may not be RiataTM but only time will tell....

PMID- 23952331
TI  - Catalytic sp3 C-H oxidation of peptides and their analogues by radical cation
      salts: from glycine amides to quinolines.
AB  - A catalytic alpha-sp(3) C-H oxidation of peptides and glycine amides was achieved
      under radical cation salt catalysis in the presence of O2, producing a series of
      substituted quinolines. The scope of this reaction shows good functional group
      tolerance and high efficiency of the oxidative functionalization. 

PMID- 23952326
TI  - Comparison of insulin degludec with insulin glargine in insulin-naive subjects
      with Type 2 diabetes: a 2-year randomized, treat-to-target trial.
AB  - AIMS: The aim of this study was to compare long-term safety and efficacy of the
      basal insulin analogue degludec with glargine in insulin-naive subjects with Type
      2 diabetes. METHODS: This open-label trial included a 52-week core period
      followed by a 52-week extension. Participants were randomized 3:1 to once-daily
      degludec or glargine, administered with metformin +/- dipeptidyl peptidase-4
      inhibitors. Basal insulin was titrated to target pre-breakfast plasma glucose 3.9
      4.9 mmol/l. RESULTS: At end of treatment (104 weeks), mean HbA1c reductions were
      similar for degludec and glargine; estimated treatment difference between
      degludec and glargine was 1 mmol/mol (95% CI -1 to 3) [0.07% (95% CI -0.07 to
      0.22)], P = 0.339 in the extension trial set (degludec 551, glargine 174),
      comprising subjects who completed core trial and continued into the extension
      trial. Overall confirmed hypoglycaemia rates (1.72 vs. 2.05 episodes/patient
      year), rates of adverse events possibly or probably related to trial product
      (0.19 events/patient-year), weight gain (2.7 vs. 2.4 kg) and mean daily insulin
      doses (0.63 U/kg) were similar between treatments in the safety analysis set
      (degludec 766, glargine 257) comprising all treated subjects. Rates of nocturnal
      confirmed hypoglycaemia (0.27 vs. 0.46 episodes/patient-year; P = 0.002) and
      severe hypoglycaemia (0.006 vs. 0.021 episodes/patient-year, P = 0.023) were
      significantly lower with degludec for the safety analysis set (analysis based on
      intention-to-treat full analysis set comprising all randomized subjects).
      CONCLUSIONS: In Type 2 diabetes, insulin degludec in combination with oral anti
      diabetic drugs, safely and effectively improves long-term glycaemic control, with
      a significantly lower risk of nocturnal hypoglycaemia as compared with glargine.

PMID- 23952332
TI  - Dicopper(II) and dizinc(II) complexes with nonsymmetric dinucleating ligands
      based on indolo[3,2-c]quinolines: synthesis, structure, cytotoxicity, and
      intracellular distribution.
AB  - Dicopper(II) and dizinc(II) complexes [Cu2((MeOOC)L(COO))(CH3COO)2] (1) and
      [Zn2((MeOOC)L(COO))(CH3COO)2] (2) were synthesized by reaction of Cu(CH3COO)2.H2O
      and Zn(CH3COO)2.2H2O with a new nonsymmetric dinucleating ligand (EtOOC)HL(COOEt)
      prepared by condensation of 6-hydrazinyl-11H-indolo[3,2-c]quinoline with diethyl
      2,2'-((3-formyl-2-hydroxy-5-methylbenzyl)azanediyl)diacetate. The design and
      synthesis of this elaborate ligand was performed with the aim of increasing the
      aqueous solubility of indolo[3,2-c]quinolines, known as biologically active
      compounds, and investigating the antiproliferative activity in human cancer cell
      lines and the cellular distribution by exploring the intrinsic fluorescence of
      the indoloquinoline scaffold. The compounds have been comprehensively
      characterized by elemental analysis, spectroscopic methods (IR, UV-vis, (1)H and
      (13)C NMR spectroscopy), ESI mass spectrometry, magnetic susceptibility
      measurements, and UV-vis complex formation studies (for 1) as well as by X-ray
      crystallography (1 and 2). The antiproliferative activity of (EtOOC)HL(COOEt), 1,
      and 2 was determined by the MTT assay in three human cancer cell lines, namely,
      A549 (nonsmall cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon
      adenocarcinoma), yielding IC50 values in the micromolar concentration range and
      showing dependence on the cell line. The effect of metal coordination on
      cytotoxicity of (EtOOC)HL(COOEt) is also discussed. The subcellular distribution
      of (EtOOC)HL(COOEt) and 2 was investigated by fluorescence microscopy, revealing
      similar localization for both compounds in cytoplasmic structures. 

PMID- 23952333
TI  - Mandibular reconstruction--biomechanical strength analysis (FEM) based on a
      retrospective clinical analysis of selected patients.
AB  - Restoration of mandible discontinuity defects continues as a challenge for
      maxillofacial surgeons. Despite the development of algorithms for reconstruction
      plates fixation and autogenous grafting techniques, complications are still
      encountered including screw loosening, bone resorption or delayed/incomplete
      union. The aim of the study was to analyze the possibility of obtaining bone
      union in the aspect of biomechanical conditions of two mandible reconstructions
      using an autogenous iliac crest bone graft stabilized with a reconstruction
      plate, and to attempt to predict patient outcomes based on strength parameters
      obtained by the finite element analysis. The authors of the present paper were
      trying to determine to what extent the reconstruction model and changes occurring
      in hard tissues of the bone and autogenous graft (simulated by changes in
      material properties) might help predict individual patient courses. The effort of
      reconstruction plates was defined using the values of the von Mises stress
      (sigmaHMH) while the effort of bones was determined based on the values of strain
      intensity epsilonint. The results of the above mentioned simulations are
      presented in the form of bar graphs and strain/stress distribution maps. Our
      strength analyses indicate that uncomplicated healing of grafts fixed with
      reconstruction plates requires that the initial loading of the stomatognatic
      system should not result in strain intensity exceeding 20-40 [*10-4]. This range
      of strain intensity evokes an increase in the mineral phase. The state of
      nonunion between the mandibular bone and the graft might result from prolonged
      periods of insufficient loading of the mandible during treatment.

PMID- 23952334
TI  - In vitro and in vivo efficacy of drugs against the protozoan parasite Azumiobodo
      hoyamushi that causes soft tunic syndrome in the edible ascidian Halocynthia
      roretzi (Drasche).
AB  - It was discovered recently that infection by a protozoan parasite, Azumiobodo
      hoyamushi, is the most probable cause for soft tunic syndrome in an edible
      ascidian, Halocynthia roretzi (Drasche). In an attempt to develop measures to
      eradicate the causative parasite, various drugs were tested for efficacy in vitro
      and in vivo. Of the 20 antiprotozoal drugs having different action mechanisms,
      five were found potent (24-h EC50  < 10 mg L(-1) ) in their parasite-killing
      effects: formalin, H2 O2 , bithionol, ClO2 and bronopol. Moderately potent drugs
      (10 < 24-h EC50  < 100 mg L(-1) ) were quinine, fumagillin, amphotericin B,
      ketoconazole, povidone-iodine, chloramine-T and benzalkonium chloride. Seven
      compounds, metronidazole, albendazole, paromomycin, nalidixic acid,
      sulfamonomethoxine, KMnO4 , potassium monopersulphate and citric acid, exhibited
      EC50  > 100 mg L(-1) . When ascidians were artificially infected with A.
      hoyamushi, treated using 40 mg L(-1) formalin, bronopol, ClO2 , or H2 O2 for 1 h
      and then monitored for 24 h, very low mortality was observed. However, the number
      of surviving parasite cells in the ascidian tunic tissues was significantly
      reduced by treating with 40 mg L(-1) formalin or ClO2 for 1 h. The data suggest
      that we might be able to develop a disinfection measure using a treatment regimen
      involving commonly available drugs. 

PMID- 23952335
TI  - Algorithm for the diagnosis of smear-negative pulmonary tuberculosis in high
      incidence resource-constrained settings.
AB  - OBJECTIVES: Diagnosis of smear-negative pulmonary tuberculosis (SNPT) remains a
      challenge, particularly in resource-constrained settings. We evaluated a
      diagnostic algorithm that combines affordable laboratory tools and a clinical
      prediction rule (CPR). METHODS: We derived, based on published evidence, a
      diagnostic algorithm for SNPT. Sputum concentration constitutes its first step.
      In suspects with negative results, SNPT probability is classified with a CPR as
      low (excluded), high (confirmed) or intermediate. For intermediate patients,
      sputum Middlebrook 7H9 liquid culture is performed, and they are assessed after 2
      weeks. If clinically deteriorated, with still negative liquid culture,
      bronchoscopy is offered. Otherwise, results of Middlebrook 7H9 culture are
      awaited. We prospectively evaluated this algorithm against a reference standard
      of solid and liquid cultures in two reference hospitals in Lima, Peru. RESULTS:
      670 SNPT suspects were included from September 2005 to March 2008. The prevalence
      of SNPT was 27% according to the reference standard. The algorithm's overall
      accuracy was 0.94 (95% CI 0.91-0.95), its sensitivity was 0.88 (95% CI 0.82-0.92)
      and its specificity, 0.96 (95% CI 0.94-0.98). Sputum concentration, the CPR,
      Middlebrook 7H9 sputum culture and bronchoscopic samples defined a diagnosis of
      SNPT according to the algorithm in 57 (37%), 25 (16%), 63 (41%) and 8(5%) of
      patients, respectively. 65% of patients were diagnosed within 3 weeks.
      CONCLUSIONS: The algorithm was accurate for SNPT diagnosis. Sputum concentration,
      CPR and selective Middlebrook 7H9 culture are essential components.

PMID- 23952336
TI  - Metabolic engineering of the C16  homoterpene TMTT in Lotus japonicus through
      overexpression of (E,E)-geranyllinalool synthase attracts generalist and
      specialist predators in different manners.
AB  - Plant defenses against herbivores include the emission of specific blends of
      volatiles, which enable plants to attract natural enemies of herbivores. We
      characterized a plastidial terpene synthase gene, PlTPS2, from lima bean
      (Phaseolus lunatus). The recombinant PlTPS2 protein was multifunctional,
      producing linalool, (E)-nerolidol and (E,E)-geranyllinalool, precursors of (E,E)
      4,8,12-trimethyltrideca-1,3,7,11-tetraene [TMTT]. Transgenic Lotus japonicus and
      Nicotiana tabacum plants, expressing PlTPS2 or its homolog Medicago truncatula
      TPS3 (MtTPS3), were produced and used for bioassays with herbivorous and
      predatory mites. Transgenic L. japonicus plants expressing PlTPS2 produced (E,E)
      geranyllinalool and TMTT, whereas wild-type plants and transgenic plants
      expressing MtTPS3 did not. Transgenic N. tabacum expressing PlTPS2 produced (E,E)
      geranyllinalool but not TMTT. Moreover, in olfactory assays, the generalist
      predatory mite Neoseiulus californicus but not the specialist Phytoseiulus
      persimilis was attracted to uninfested, transgenic L. japonicus plants expressing
      PlTPS2 over wild-type plants. The specialist P. persimilis was more strongly
      attracted by the transgenic plants infested with spider mites than by infested
      wild-type plants. Predator responses to transgenic plant volatile TMTT depend on
      various background volatiles endogenously produced by the transgenic plants.
      Therefore, the manipulation of TMTT is an ideal platform for pest control via the
      attraction of generalist and specialist predators in different manners. 

PMID- 23952337
TI  - Osteoporosis in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is being regarded as a heterogeneous
      disease with clinically significant pulmonary and extrapulmonary manifestations,
      such as emphysema, cardiovascular disease and osteoporosis. Osteoporosis is
      characterized by low bone mass and microarchitectural deterioration of bone
      tissue, leading to enhanced bone fragility and, consequently, an increased risk
      of fracture. Fractures resulting from osteoporosis might contribute to increased
      morbidity and mortality, particularly in COPD patients. The high prevalence of
      osteoporosis in COPD patients is assumed to be due to common risk factors, such
      as older age and tobacco smoking, and COPD-specific risk factors, such as
      systemic inflammation, vitamin D deficiency and the use of oral or inhaled
      corticosteroids. This review provides a state-of-the-art summary of the
      prevalence, pathophysiology, diagnosis, risk factors and treatment of
      osteoporosis in COPD patients. It also discusses potential mechanisms linking
      COPD with osteoporosis.

PMID- 23952338
TI  - Finding atrial fibrillation: just keep looking, just keep looking ... (but
      remember stroke prevention).

PMID- 23952340
TI  - Pain-relieving effects of pulsed magnetic fields in a rat model of carrageenan
      induced hindpaw inflammation.
AB  - PURPOSE: Many strategies have been investigated to exclude the several side
      effects of pharmacological or invasive treatments. Non-invasive pulsed magnetic
      field (PMF) treatment with no toxicity or side-effects can be an alternative to
      pharmacologic treatments. The purpose of this study was, therefore, to
      investigate the pain-relieving effects of PMF treatment in the inflammatory pain
      conditions. MATERIALS AND METHODS: Effects of PMF treatment on the hallmarks of
      the inflammatory pain indices such as hyperalgesia, allodynia, edema and several
      biochemical parameters that evaluate oxidative stress were investigated using a
      well established carrageenan (CAR)-induced hindpaw inflammation model in rats.
      RESULTS: CAR injection lowered the paw withdrawal thermal latencies
      (hyperalgesia) and mechanical thresholds (allodynia). CAR also decreased the
      superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)
      levels and increased malondialdehyde (MDA) levels compared with healthy rat paw
      tissues. PMF treatment produced significant increases in the thermal latencies
      and mechanical thresholds in CAR-injected paws. In the inflamed paw tissues, PMF
      increased the activities of SOD, CAT and GPx and decreased MDA level. We also
      demonstrated that PMF decreased paw mass indicating that it has an anti-edematous
      potential. CONCLUSIONS: The present results reveal that PMF treatment can
      ameliorate the CAR-induced inflammatory pain indices such as mechanical
      allodynia, thermal hyperalgesia and edema, and attenuate the oxidative stress.
      The action mechanisms of PMF in CAR-induced inflammation might be related to the
      increases in the levels of antioxidant enzymes in inflamed tissues. The findings
      suggest that PMF treatment might be beneficial in inflammatory pain conditions.

PMID- 23952339
TI  - Dimorphic HLA-B signal peptides differentially influence HLA-E- and natural
      killer cell-mediated cytolysis of HIV-1-infected target cells.
AB  - As a mechanism of self-protection, signal peptides cleaved from human leukocyte
      antigen (HLA) class I products bind to HLA-E before the complex interacts with
      the natural killer (NK) cell receptor CD94/NKG2A to inhibit NK-mediated cell
      lysis. Two types of the signal peptides differ in their position 2 (P2) anchor
      residue, with P2-methionine (P2-M) having higher HLA-E binding affinity than P2
      threonine (P2-T). All HLA-A and HLA-C molecules carry P2-M, whereas HLA-B
      products have either P2-M or P2-T. Epidemiological evidence suggests that P2-M is
      unfavourable in the context of HIV-1 infection, being associated with accelerated
      acquisition of HIV-1 infection in two African cohorts. To begin elucidating the
      functional mechanism, we studied NK-mediated killing of CD4(+) T cells and
      monocyte-derived macrophages infected with two laboratory-adapted HIV-1 strains
      and two transmitted/founder (T/F) viruses. In the presence of target cells
      derived from individuals with the three HLA-B P2 genotypes (M/M, M/T and T/T), NK
      mediated cytolysis was elevated consistently for P2-T in a dose-dependent manner
      for all cell and virus combinations tested (P = 0.008-0.03). Treatment of target
      cells with an anti-HLA-E monoclonal antibody restored NK-mediated cytolysis of
      cells expressing P2-M. Observations on cell lysis were also substantiated by
      measurements of HIV-1 p24 antigen in the culture supernatants. Overall, our
      experiments indicate that the anti-HIV-1 function mediated by NK cells is
      compromised by P2-M, corroborating the association of HLA-B genotype encoding P2
      M with accelerated HIV-1 acquisition. 

PMID- 23952341
TI  - Complexes of dual-function hemoglobin/dehaloperoxidase with substrate 2,4,6
      trichlorophenol are inhibitory and indicate binding of halophenol to compound I.
AB  - The hemoglobin of sea worm Amphitrite ornata, which for historical reasons is
      abbreviated as DHP for dehaloperoxidase, has two physiological functions: it
      binds dioxygen in the ferrous state and dehalogenates halophenols, such as 2,4,6
      trichlorophenol (TCP), using hydrogen peroxide as the oxidant in the ferric
      state. The crystal structures of three DHP variants (Y34N, Y34N/S91G, and L100F)
      with TCP bound show two mutually exclusive modes of substrate binding. One of
      them, the internal site, is deep inside the distal pocket with the phenolic OH
      moiety forming a hydrogen bond to the water molecule coordinated to the heme Fe.
      In this complex, the distal histidine is predominantly located in the closed
      position and also forms a hydrogen bond to the phenolic hydroxide. The second
      mode of TCP binding is external, at the heme edge, with the halophenol molecule
      forming a lid covering the entrance to the distal cavity. The distal histidine is
      in the open position and forms a hydrogen bond to the OH group of TCP, which also
      hydrogen bonds to the hydroxyl of Tyr38. The distance between the Cl4 atom of TCP
      and the heme Fe is 3.9 A (nonbonding). In both complexes, TCP molecules prevent
      the approach of hydrogen peroxide to the heme, indicating that the complexes are
      inhibitory and implying that the substrates must bind in an ordered fashion:
      hydrogen peroxide first and TCP second. Kinetic studies confirmed the inhibition
      of DHP by high concentrations of TCP. The external binding mode may resemble the
      interaction of TCP with Compound I, the catalytic intermediate to which
      halophenols bind. The measured values of the apparent Km for TCP were in the
      range of 0.3-0.8 mM, much lower than the concentrations required to observe TCP
      binding in crystals. This indicates that during catalysis TCP binds to Compound
      I. Mutant F21W, which likely has the internal TCP binding site blocked, has ~7%
      of the activity of wild-type DHP.

PMID- 23952342
TI  - Platform for high-throughput testing of the effect of soluble compounds on 3D
      cell cultures.
AB  - In vitro 3D culture could provide an important model of tissues in vivo, but
      assessing the effects of chemical compounds on cells in specific regions of 3D
      culture requires physical isolation of cells and thus currently relies mostly on
      delicate and low-throughput methods. This paper describes a technique ("cells-in
      gels-in-paper", CiGiP) that permits rapid assembly of arrays of 3D cell cultures
      and convenient isolation of cells from specific regions of these cultures. The 3D
      cultures were generated by stacking sheets of 200-MUm-thick paper, each sheet
      supporting 96 individual "spots" (thin circular slabs) of hydrogels containing
      cells, separated by hydrophobic material (wax, PDMS) impermeable to aqueous
      solutions, and hydrophilic and most hydrophobic solutes. A custom-made 96-well
      holder isolated the cell-containing zones from each other. Each well contained
      media to which a different compound could be added. After culture and disassembly
      of the holder, peeling the layers apart "sectioned" the individual 3D cultures
      into 200-MUm-thick sections which were easy to analyze using 2D imaging (e.g.,
      with a commercial gel scanner). This 96-well holder brings new utilities to high
      throughput, cell-based screening, by combining the simplicity of CiGiP with the
      convenience of a microtiter plate. This work demonstrated the potential of this
      type of assays by examining the cytotoxic effects of phenylarsine oxide (PAO) and
      cyclophosphamide (CPA) on human breast cancer cells positioned at different
      separations from culture media in 3D cultures. 

PMID- 23952343
TI  - Use of metabolic profiling to study grape skin polyphenol behavior as a result of
      canopy microclimate manipulation in a 'Pinot noir' vineyard.
AB  - Canopy microclimate manipulation can have a significant effect on grapevine gene
      expression and can thus affect the yield of many important berry compounds.
      Focusing on only a few targeted phenolics in the past, advanced multimethod
      analytical approaches are opening up much wider possibilities to fill in the gaps
      of missing knowledge about plant secondary metabolism. Different leaf removal
      timings, leading to different microclimate scenarios, were thus introduced in a
      'Pinot noir' vineyard to reveal related alterations of multiple classes of skin
      phenolics, including some rarely studied to date. Different accumulation trends
      during cluster development were detected not only between groups but also between
      individual compounds within groups. Although many significant changes were
      observed early in the season, these were later often less significant. However,
      at harvest, 31 of 72 detected compounds showed significant differences in
      comparison to control for at least one of three leaf removal approaches. 

PMID- 23952344
TI  - Young children with cerebral palsy: families self-reported equipment needs and
      out-of-pocket expenditure.
AB  - BACKGROUND: Costs to families raising a child with cerebral palsy and complex
      needs are direct and indirect. This study investigated the self-reported real
      life costs, equipment needs, and associated characteristics of children who had
      the highest equipment and care needs. METHOD: The purposive sample (n = 29) were
      families with a child with cerebral palsy: gross motor function levels 5 (n =
      20), level 4 (n = 5), level 3 (n = 4); complex communication needs (n = 21);
      medical needs (n = 14); hearing impairment (n = 5) and visual impairment (n = 9).
      Participants completed a specifically designed survey that included the
      Assistance to Participate Scale. Equipment and technology purchases were recorded
      in the areas of positioning, mobility, transport, home modifications,
      communication, splinting and orthoses, self-care, technology, communication
      devices, medical, adapted toys/leisure items and privately hired
      babysitters/carers. Descriptive and inferential statistics were used to analyse
      the data. RESULTS: Families had purchased up to 25 items within the areas
      described. The highest median number of items were recorded for positioning (15
      items), mobility devices (9 items) and adapted toys/leisure items (9 items).
      Median costs were highest for home modifications (AUD$23000), transport
      (AUD$15000), splints and orthoses (AUD$3145), paid carers (AUD$3080), equipment
      for toileting/dressing/bathing (AUD$2900) and technical/medical items ($2380).
      Children who needed more parental assistance to participate in play and
      recreation also required significantly more equipment overall for positioning,
      communication, self-care and toys/leisure. CONCLUSIONS: The equipment needs of
      young children with complex disability are extensive and out-of-pocket expenses
      and parental time to support participation in play/recreation excessive.
      Substantial financial support to offset costs are crucial to better support
      families in this life situation.

PMID- 23952345
TI  - Safe single-dose administration of propofol in patients with established Brugada
      syndrome: a retrospective database analysis.
AB  - BACKGROUND: Propofol is an anesthetic drug with a very attractive pharmacokinetic
      profile, which makes it the induction agent of choice, especially in day-case
      surgery. Data on its potential proarrhythmic effects in patients with Brugada
      syndrome (BS) patients are still lacking. The aim of our study was to investigate
      whether a single dose of propofol triggered any adverse events in consecutive
      high-risk patients with BS. METHODS: All consecutive patients with BS having
      undergone an implantable cardiac defibrillator implantation under general
      anesthesia were eligible for this study. The anesthetic chart of each patient was
      reviewed, and the occurrence of malignant arrhythmic events as well as the need
      for defibrillation during induction and maintenance of anesthesia was
      investigated. Further monitoring of the patient comprised five-lead
      electrocardiogram (ECG), pulse oxymetry, and continuous carbon dioxide monitoring
      through side sampling from the ventilator tubes. Anesthesia was induced with
      propofol and sufentanyl. Injection of propofol occurred in a single-shot bolus-as
      often performed by most anesthetists-over a few seconds. Anesthesia was
      maintained with volatile anesthetics (sevoflurane or desflurane) in an oxygen-air
      mixture. RESULTS: From 1996 to 2011, 57 high-risk patients with BS (35 males;
      mean age: 43 +/- 16 years) underwent an automated implantable cardioverter
      defibrillator implantation at our center using propofol as induction drug of
      general anesthesia. Three patients had a history of spontaneous type I ECG, three
      had aborted sudden death, and 51 had a history of recurrent or unexplained
      syncope. The induction dose ranged between 0.8 mg/kg and 5.0 mg/kg (2.2 +/- 0.7
      mg/kg). Only one case received propofol to maintain anesthesia. The surgical
      procedure involved an anesthetic period of 75 +/- 25 minutes. No patient
      developed a malignant rhythm during induction and maintenance of anesthesia. All
      patients were then safely discharged from the postanesthetic care unit after 1
      hour. No adverse events were noticed during the recovery phase. In our study,
      administration of a single-dose propofol in patients with BS was safe.
      Nevertheless, extreme caution is still recommended when conducting general
      anesthesia in patients with BS, especially if BS patients are sedated with
      propofol for longer periods.

PMID- 23952347
TI  - From the editor's desk.
AB  - No abstract available for this article. 

PMID- 23952346
TI  - Body temperature, activity and melatonin profiles in adults with attention
      deficit/hyperactivity disorder and delayed sleep: a case-control study.
AB  - Irregular sleep-wake patterns and delayed sleep times are common in adults with
      attention-deficit/hyperactivity disorder, but mechanisms underlying these
      problems are unknown. The present case-control study examined whether circadian
      abnormalities underlie these sleep problems in a naturalistic home setting. We
      included 12 medication-naive patients with attention-deficit/hyperactivity
      disorder and delayed sleep phase syndrome, and 12 matched healthy controls. We
      examined associations between sleep/wake rhythm in attention
      deficit/hyperactivity disorder and circadian parameters (i.e. salivary melatonin
      concentrations, core and skin temperatures, and activity patterns) of the
      patients and controls during five consecutive days and nights. Daily bedtimes
      were more variable within patients compared with controls (F = 8.19, P < 0.001),
      but melatonin profiles were equally stable within individuals. Dim-light
      melatonin onset was about 1.5 h later in the patient group (U = 771, Z = -4.63, P
      < 0.001). Patients slept about 1 h less on nights before work days compared with
      controls (F = 11.21, P = 0.002). The interval between dim-light melatonin onset
      and sleep onset was on average 1 h longer in patients compared with controls (U =
      1117, Z = -2.62, P = 0.009). This interval was even longer in patients with
      extremely late chronotype. Melatonin, activity and body temperatures were delayed
      to comparable degrees in patients. Overall temperatures were lower in patients
      than controls. Sleep-onset difficulties correlated with greater distal-proximal
      temperature gradient (DPG; i.e. colder hands, r(2)  = -0.32, P = 0.028) in
      patients. Observed day-to-day bedtime variability of individuals with attention
      deficit/hyperactivity disorder and delayed sleep phase syndrome were not
      reflected in their melatonin profiles. Irregular sleep-wake patterns and delayed
      sleep in individuals with attention-deficit/hyperactivity disorder and delayed
      sleep phase syndrome are associated with delays and dysregulations of the core
      and skin temperatures. 

PMID- 23952348
TI  - Culture:.
AB  - Culture is defined and discussed as an important ingredient to treatment
      planning. Components of culture are identified and examples of how they pertain
      to treatment are given through a brief case example. 

PMID- 23952349
TI  - Culture and communication in the treatment planning for occupational therapy with
      minority patients.
AB  - Ethnic minority populations are increasing in health care delivery systems.
      Statistics show that ethnic minorities have a greater need for health care but
      have not received comparable services as those afforded to the white middle class
      majority. This paper provides information on the characteristics, health beliefs
      and practices of Hispanic, Indochinese, Asians (Japanese, Chinese and Filipinos)
      and Black Americans. Effective treatment planning is contingent upon the
      recognition of these beliefs and cultural values. Strategies for intercultural
      communication as a guide to promoting better occupational therapy services to
      ethnic minorities will be provided. 

PMID- 23952350
TI  - Ethnic/Racial considerations in occupational therapy:.
AB  - Examination of the occupational therapy literature related to cultural facotrs in
      treatment inspired investigation into the levels of cultural awareness of
      currently practicing therapists. White, black, Asian-American, Puerto Rican and
      Mexican-American therapists were selected to receive a questionaire involving
      factors that encourage or discourage cultural sensitivity in the clinical
      setting. Some of the results of the study will be reported and discussed. 

PMID- 23952351
TI  - A new social perspective on disability and its implications for rehabilitation.
AB  - As disabled people become more active and vocal in asserting their rights, they
      are sharing important information about the experience of disability in our
      society. In fact, they are challenging the defintions and models of disability
      traditionally utilized in rehabilitation practice. This paper contrasts the
      traditional medical model of disability with a new interactional or socio
      political model. The experience of disability is examined in the context of
      disabled people's minority group status. Also discussed are the efforts of
      disabled persons to fashion a positive identity and sense of cultural pride.
      Arguments are presented for addressing the social aspects of disability in
      rehabilitation. 

PMID- 23952352
TI  - Appalachian values:.
AB  - Appalachia is a distinct geographic region within the United States and natives
      of this region live within a separate subculture. Initially, inhabitants of this
      region shared the values of many other early American settlers. However, in time
      the relative isolation of this region produced a dichotomy between the way of
      life in and increasingly technological American society and that found within the
      slower changing region of Appalachia. Thus, values of Appalachian people today
      reflect these continued differences. Occupational therapists treating patients
      from Appalachia need to understand the values of this subsulture in order to
      assess their patients accurately and to provide culturally appropriate treatment.
      This paper presents an overview of Appalachian values, with implications for
      occupational therapy. 

PMID- 23952353
TI  - Implications of the model of human occupation for intervention with native
      canadians.
AB  - The following paper provides a theoretical framework for occuaptional therapy
      with Native Canadians. Traditional models of care have not been entirely
      satisfactory with this population, as they have failed to come to terms with
      cultural issues and to recognize cultural stereotyping. NAtive culture is first
      explored, both from a traditional and a transitional standpoint, with a focus on
      issues which are of particular interest to occupational therapy, such as role
      performance, role learning, work patterns, and interpersonal patterns. The Model
      of Human Occupation is then applied to dysfunction in this population, with
      particular emphasis on psychosocial dysfunction. Several basic principles in
      occupational therapy are examined with relation to Native culture. Finally, the
      various subsystems of the model, and their interpretation for this population are
      discussed. 

PMID- 23952354
TI  - A cross-cultural investigation of occupational role.
AB  - The occuptaional behavior approach has been proposed as a generic frame of
      reference for occupational therapy, yet it has not specifically addressed the
      influence of cultural variation on its theory base. This article critically
      investigates the concept of occupational role, one of its central concepts, from
      a cross-cultural point of view. The literature on role theory and on Hispanic and
      Anglo-American values is reviewed. A study which described the occupational role
      enactment of a physically disabled Colombian adolescent female using the life
      history methos is then discussed in terms of this literature. Finally, cultural
      implications for theory development in this area are identified. 

PMID- 23952355
TI  - A cultural intervention model for developmentally disabled adults:.
AB  - This paper describes Chavarim, a non-traditional community based program, founded
      in the Jewish cultural context. Chavarim is a socialization and life-skill
      development program for Jewish adults with developmental disabilities. The
      program incorporates occupational therapy precepts of independent living,
      community integration, cultural identification and development of life roles.
      Specific details of program development and implementation will be included.
      While this paper is concerned with service delivery in the area of developmental
      disabilities, recommendation for the applicability of the model for occupational
      therapy intervention with other cultural groups will be discussed. In this
      author's opinion, for a person with a disability to be adequately prepared to
      meet the challenges of full community integration, the meaning of culture in
      daily life must be understood and incorporated into life-skill training programs.
      This is an account of how one occupational therapist developed an innovative
      program to meet the challenge of the task. 

PMID- 23952356
TI  - Cultural implications in treatment of Japanese american patients.
AB  - Therapists encounter patients from varying cultural backgrounds. The values of
      occupational therapy parallel that of the Anglo American culture, i.e.,
      independence, self-inititation, and internal motivation. To be truly effective as
      therapists it is important to be cognizant of how values and cultural aspects
      influence interactions, treatment, and perceptions of ability and disability. The
      purpose of this paper is to explore some of the values in the Japanese American
      culture, particularly the second generation (generally 40-65 years of age).
      Values such as deference, dependence, hierarchy, duty and obligation, and
      external motivation are discussed along with treatment implications and
      recommendations for treatment. 

PMID- 23952357
TI  - Patient compliance in occupational therapy home health programs:.
AB  - Home health is by definition intermittent treatment. The voluntary participation
      of the patient and family in working toward goal achievement, especially in the
      absence of the practitioner, greatly affects the effectiveness of the
      occupational therpist. Improving that participation requires a thoughtful
      understanding of the value system of the patient and creative, flexible
      programming. The unique effects that the sociocultural experiences of patients
      have on the treatment process in home health care are discussed according to a
      set of facotrs that influence his compliance with care. Research findings and a
      brief case study shall illustrate some of the factors. 

PMID- 23952358
TI  - Beyond eating skills:.
AB  - In eating skills programs, the tendency is to address the presenting physical
      problems by providing therapy or equipment to enable the patient to bring food to
      the mouth, chew, and swallow independently. To aid in more comprehensive
      treatment planning, ten categories of mealtime activities are described.
      Empahasis is placed on individualization of treatment by considering personal
      lifestyles and preferences. An interdisciplinary approach is described, as well
      as the importance of involving families. 

PMID- 23952359
TI  - Sexual consequences of disability:.
AB  - No abstract available for this article. 

PMID- 23952360
TI  - Wellness:.
AB  - The American health care system has gone through various stages of development
      over the past decades. The stages range from a physician dominated medical model
      to the currently emerging Wellness era in which alternative delivery systems are
      being designed. These changes in the direction of health care are designed to
      reduce health care costs and also to promote healthier life styles. Wellness,
      however, is not a new concept. Occupational therapy has espoused and practiced
      its principles since its inception as a profession over seventy years ago. This
      paper looks at the historical development of the health care system and relates
      the growth of the wellness movement to occupational therapy practice. It suggests
      that the profession was a forerunner to current wellness activity. Finally, it
      explores research projects and the creation of occupational therapy positions and
      curricular alterations to meet the needs of the current wellness movement. 

PMID- 23952362
TI  - Prevalence and characterization of cefotaxime and ciprofloxacin co-resistant
      Escherichia coli isolates in retail chicken carcasses and Ground Pork, China.
AB  - Retail meat products could serve as an important medium for the transfer of
      multidrug resistant isolates from food-producing animals to the community. In
      this study, the prevalence and characteristics of cefotaxime and ciprofloxacin co
      resistant Escherichia coli isolates were investigated in retail chicken and
      ground pork samples from four provinces of China. The isolates were subjected to
      phylogenetic group typing and antimicrobial susceptibility testing. All isolates
      were further characterized by pulsed-field gel electrophoresis to determine the
      genetic relatedness. These isolates were also screened for beta-lactamase genes,
      quinolone resistance determinants by PCR, and followed by DNA sequence analysis.
      Cefotaxime and ciprofloxacin co-resistant E. coli isolates with diverse genetic
      origins were recovered in 31.9% (106/332) of retail meat samples. E. coli
      isolates of phylogenetic group A were dominant (59.4%, 63/106), and all isolates
      showed multidrug resistant profiles. The dominant resistant profiles were AMP-CAZ
      CTX-CIP-CHL-GEN-SXT-TET (n=43) and AMP-CAZ-CTX-CIP-CHL-SXT-TET (n=43). Point
      mutations in quinolone resistance determination regions of topoisomerases were
      identified in all the isolates, and most of the isolates accumulated three (n=78)
      or four (n=21) point mutations. Plasmid-mediated quinolone-resistant determinants
      were identified in 68 isolates, including oqxAB (n=66), qnrS1 (n=7), qnrS2 (n=4),
      and aac(6')-Ib-cr (n=9). Eight subtypes of bla(CTX-M) were identified in 103 E.
      coli isolates, and blaCTX-M-55 (n=90) was dominant. This study highlights that
      retail meat could serve as an important reservoir of cefotaxime and ciprofloxacin
      co-resistant E. coli isolates. It is necessary to evaluate their contribution in
      the community and hospital infections.

PMID- 23952363
TI  - Characterization of ESBLs and associated quinolone resistance in Escherichia coli
      and Klebsiella pneumoniae isolates from an urban wastewater treatment plant in
      Algeria.
AB  - The aim of the study was the characterization of extended spectrum beta
      lactamases (ESBLs) and quinolone resistance in cefotaxime-resistant coliform
      isolates from a wastewater treatment plant (WWTP). ESBLs were detected in 19 out
      of 24 isolates (79%) from raw water and in 21 out of 24 isolates (87.5%) from
      treated water, identified as Klebsiella pneumoniae and Escherichia coli.
      Molecular characterization of ESBLs and quinolone resistance showed allele
      profiles CTX-M-15 (3), CTX-M-3 (5), CTX-M-15+qnrB1 (1), CTX-M-3+qnrB1 (1), CTX-M
      15+aac-(6')-Ib-cr (4), and CTX-M-15+qnrB1+aac-(6')-Ib-cr (7). A double mutation
      S83L and D87N (GyrA) and a single mutation S80I (ParC) were detected in
      ciprofloxacin-resistant E. coli isolates. In K. pneumoniae, mutations S83I
      (GyrA)+S80I (ParC) or single S80I mutation were detected in ciprofloxacin
      resistant isolates, and no mutation was observed in ciprofloxacin-susceptible
      isolates. bla(CTX-M), qnrB1, and aac-(6')-Ib-cr were found, respectively, in
      these genetic environments: ISEcp1-bla(CTX-M)-orf477, orf1005-orf1-qnrB1, and
      Tn1721-IS26-aac-(6')-Ib-cr-bla(OXA-1)-catB4. bla(CTX-M-15) was located on IncF
      plasmid in E. coli and bla(CTX-M-3) on IncL/M plasmid in both species (E. coli
      and K. pneumoniae). E. coli isolates were affiliated to the phylogroups/MLST:
      D/ST405 (CC405), A/ST10 (CC10), A/ST617 (CC10), and B1/ST1431. K. pneumoniae
      isolates belonged to phylogroup KpI and to sequence types ST15, ST17, ST36, ST48,
      ST54, and ST147. The study showed a multi-drug resistance at the inflow and
      outflow of the WWTP, with ESBL production, plasmid-mediated quinolones
      resistance, and mutations in topoisomerases. The findings highlight the
      similarity of antibiotic resistance mechanisms in the clinical setting and the
      environment, and the role of the latter as a source of dissemination of
      resistance genes.

PMID- 23952364
TI  - Response to Lie et al. Preventing Type 2 diabetes after gestational diabetes:
      women's experiences and implications for diabetes prevention interventions.

PMID- 23952365
TI  - Dermatologic adverse effect of subcutaneous furosemide administration in a dog.

PMID- 23952366
TI  - Sex-specific interaction effects of age, occupational status, and workplace
      stress on psychiatric symptoms and allostatic load among healthy Montreal
      workers.
AB  - Socio-demographics and workplace stress may affect men and women differently. The
      aim of this cross-sectional study was to assess sex-specific interactions among
      age, occupational status, and workplace Demand-Control-Support (D-C-S) factors in
      relation to psychiatric symptoms and allostatic load levels representing multi
      systemic "wear and tear". It was hypothesized that beyond main effects, D-C-S
      factors would be moderated by occupational status and age in sex-specific
      directions predictive of subjective psychiatric symptoms and objective
      physiological dysregulations. Participants included healthy male (n = 81) and
      female (n = 118) Montreal workers aged 20 to 64 years (Men: M = 39.4 years, SD =
      11.3; Women: M = 42.8 years, SD = 11.38). The Job Content Questionnaire was
      administered to assess workplace D-C-S factors that included psychological
      demands, decisional latitude, and social support. Occupational status was coded
      using the Nam--Powers--Boyd system derived from the Canadian census. Psychiatric
      symptoms were assessed using the Beck Anxiety Scale and the Beck Depression
      Inventory II. Sex-specific allostatic load indices were calculated based on
      fifteen biomarkers. Regression analyses revealed that higher social support was
      associated with less depressive symptoms in middle aged (p = 0.033) and older men
      (p = 0.027). Higher occupational status was associated with higher allostatic
      load levels for men (p = 0.035), while the reverse occurred for women (p =
      0.048). Women with lower occupational status but with higher decision latitude
      had lower allostatic load levels, as did middle-aged (p = 0.031) and older women
      (p = 0.003) with higher psychological demands. In summary, age and occupational
      status moderated workplace stress in sex-specific ways that have occupational
      health implications.

PMID- 23952367
TI  - Development of a short questionnaire to identify the risk of nonadherence to
      antibiotic treatment.
AB  - OBJECTIVE: Nonadherence to the prescribed antibiotic treatment is a widespread
      problem, affecting not only individual patients, but also public health. As
      measures to predict it are still lacking, we aimed to design an instrument to
      identify nonadherence risk in short-term antibiotic therapies. METHODS: Patient
      adherence was assessed by pill count and an extensive set of standardized
      questions, newly developed according to the five-dimension adherence model
      proposed by the World Health Organization. It combined previously validated
      questionnaires and original questions adapted from our exploratory survey. The
      extensive set was analyzed prospectively in adult patients treated with
      antibiotics in outpatient settings. The number of items was reduced stepwise
      keeping as many of five factor subgroups as possible. The items were dichotomized
      as positive (indicating nonadherence risk) or negative. RESULTS: One third (32%)
      of the respondents (N = 122) did not adhere to the prescribed antibiotic regimen.
      The extensive set of questions was reduced to a short questionnaire. It consisted
      of four items independently associated with nonadherence (P < 0.05) and covered
      three of the five analyzed factor subgroups: healthcare-related factor
      (consultations about medicines), therapy-related factor (complexity of
      treatment), and patient-related factors (forgetfulness, health behavior). The sum
      of 0-1 positive answers indicated an adherent patient, and 2-4 a risky patient.
      Such a differential approach led to relatively good sensitivity, specificity, and
      total predictive value (80%, 82%, and 81%, respectively) in our sample.
      CONCLUSION: The short measure representing the multiple factor subgroups was
      developed to identify nonadherence to antibiotic treatment with acceptable levels
      of sensitivity, specificity, and predictive values. It could be valuable for
      healthcare professionals, especially in primary healthcare. Considering
      limitations of the study (medium sample size, justification of patient's
      responses, no re-test), future studies could continue investigations on the
      validity and elaboration of this instrument in larger samples.

PMID- 23952368
TI  - Molecular interactions, proton exchange, and photoinduced processes prompted by
      an inclusion process and a [2]pseudorotaxane formation.
AB  - Appropriate design of the host and guest components allows formation of a novel
      [2]pseudorotaxane complex with an interrupted photoinduced electron transfer
      (PET)-coupled fluorescence resonance energy transfer (FRET) response. This is the
      first example of an inclusion complex with NO6-based azacrown ether as the host
      unit (H). Different guest molecules (G1, G2, G3, and G4) with varying stopper
      size are used for the studies. Unlike G1, G2, and G3, G4 with a relatively
      bulkier stopper fails to form a [2]pseudorotaxane complex. Isothermal titration
      microcalorimetry measurements reveal a systematic increase in the association
      constant for H.G1, H.G2, and H.G3 with a change in the stopper size.
      Thermodynamic data suggest that the formation of H.G1/H.G2/H.G3 is exclusively
      driven by a large positive entropic gain (TDeltaS = 19.69/26.80/21.81 kJ.mol(
      1)), while the enthalpy change is slightly negative for H.G1/H.G3 (-2.61/-1.97
      kJ.mol(-1)) and slightly positive for H.G2 (DeltaH = 5.98 kJ.mol(-1)). For these
      three inclusion complexes, an interrupted PET-coupled FRET response is observed
      with varying efficiency, which is attributed to the subtle differences in acidity
      of the NH2(+) unit of the guest molecules and thus the proton exchange ability
      between the host and respective guest. This is substantiated by the results of
      the computational studies. 

PMID- 23952369
TI  - Limits on violations of Lorentz symmetry and the Einstein equivalence principle
      using radio-frequency spectroscopy of atomic dysprosium.
AB  - We report a joint test of local Lorentz invariance and the Einstein equivalence
      principle for electrons, using long-term measurements of the transition frequency
      between two nearly degenerate states of atomic dysprosium. We present many-body
      calculations which demonstrate that the energy splitting of these states is
      particularly sensitive to violations of both special and general relativity. We
      limit Lorentz violation for electrons at the level of 10(-17), matching or
      improving the best laboratory and astrophysical limits by up to a factor of 10,
      and improve bounds on gravitational redshift anomalies for electrons by 2 orders
      of magnitude, to 10(-8). With some enhancements, our experiment may be sensitive
      to Lorentz violation at the level of 9 * 10(-20).

PMID- 23952370
TI  - Feshbach projection formalism for open quantum systems.
AB  - We provide a new approach to open quantum systems which is based on the Feshbach
      projection method. Instead of looking for a master equation for the dynamical map
      acting in the space of density operators we provide the corresponding equation
      for the evolution in the Hilbert space of the amplitude operators. Its solution
      enables one to construct a legitimate quantum evolution (completely positive and
      trace preserving). Our approach, contrary to the standard Nakajima-Zwanzig
      method, allows for a series of consistent approximations resulting in a
      legitimate quantum evolution. The new scheme is illustrated by the well-known
      spin-boson model beyond the rotating wave approximation. It is shown that the
      presence of counterrotating terms dramatically changes the asymptotic evolution
      of the system. 

PMID- 23952371
TI  - Fluctuation-dissipation theorem in an isolated system of quantum dipolar bosons
      after a quench.
AB  - We examine the validity of fluctuation-dissipation relations in isolated quantum
      systems taken out of equilibrium by a sudden quench. We focus on the dynamics of
      trapped hard-core bosons in one-dimensional lattices with dipolar interactions
      whose strength is changed during the quench. We find indications that fluctuation
      dissipation relations hold if the system is nonintegrable after the quench, as
      well as if it is integrable after the quench if the initial state is an
      equilibrium state of a nonintegrable Hamiltonian. On the other hand, we find
      indications that they fail if the system is integrable both before and after
      quenching. 

PMID- 23952372
TI  - Robust quantum control by a single-shot shaped pulse.
AB  - Considering the problem of the control of a two-state quantum system by an
      external field, we establish a general and versatile method allowing the
      derivation of smooth pulses which feature the properties of high fidelity,
      robustness, and low area. Such shaped pulses can be interpreted as a single-shot
      generalization of the composite pulse-sequence technique with a time-dependent
      phase. 

PMID- 23952373
TI  - Experimental distillation of quantum nonlocality.
AB  - We report the first experimental demonstration of distillation of quantum
      nonlocality, confirming the recent theoretical protocol [Phys. Rev. Lett. 102,
      120401 (2009)]. Quantum nonlocality is described by a correlation box with binary
      inputs and outputs, and the nonlocal boxes are realized through appropriate
      measurements on polarization entangled photon pairs. We demonstrate that
      nonlocality is amplified by connecting two nonlocal boxes into a composite one
      through local operations and four-photon measurements. 

PMID- 23952374
TI  - Universal superfluid transition and transport properties of two-dimensional dirty
      bosons.
AB  - We study the phase diagram of two-dimensional, interacting bosons in the presence
      of a correlated disorder in continuous space, by using large-scale quantum Monte
      Carlo simulations at finite temperature. We show that the superfluid transition
      is strongly protected against disorder. It remains of the Berezinskii-Kosterlitz
      Thouless type up to disorder strengths comparable to the chemical potential.
      Moreover, we study the transport properties in the strong disorder regime where a
      zero-temperature Bose-glass phase is expected. We show that the conductance
      exhibits a thermally activated behavior vanishing only at zero temperature. Our
      results point towards the existence of a Bose bad-metal phase as a precursor of
      the Bose-glass phase.

PMID- 23952375
TI  - Quantum-dot-based resonant exchange qubit.
AB  - We introduce a solid-state qubit in which exchange interactions among confined
      electrons provide both the static longitudinal field and the oscillatory
      transverse field, allowing rapid and full qubit control via rf gate-voltage
      pulses. We demonstrate two-axis control at a detuning sweet spot, where leakage
      due to hyperfine coupling is suppressed by the large exchange gap. A pi/2-gate
      time of 2.5 ns and a coherence time of 19 MUs, using multipulse echo, are also
      demonstrated. Model calculations that include effects of hyperfine noise are in
      excellent quantitative agreement with experiment.

PMID- 23952376
TI  - Electrically protected resonant exchange qubits in triple quantum dots.
AB  - We present a modulated microwave approach for quantum computing with qubits
      comprising three spins in a triple quantum dot. This approach includes single-
      and two-qubit gates that are protected against low-frequency electrical noise,
      due to an operating point with a narrowband response to high frequency electric
      fields. Furthermore, existing double quantum dot advances, including robust
      preparation and measurement via spin-to-charge conversion, are immediately
      applicable to the new qubit. Finally, the electric dipole terms implicit in the
      high frequency coupling enable strong coupling with superconducting microwave
      resonators, leading to more robust two-qubit gates. 

PMID- 23952377
TI  - Two-qubit gates for resonant exchange qubits.
AB  - A new approach to single-qubit operations using exchange interactions of single
      electrons in gate-defined quantum dots has recently been demonstrated: the
      resonant exchange qubit. We show that two-qubit operations, specifically the
      controlled phase gate, can be performed between resonant exchange qubits very
      straightforwardly, using a single exchange pulse. This is in marked contrast to
      the best known protocols for exchange qubits where such a gate requires many
      pulses so that leakage processes arising from the exchange interaction can be
      overcome. For resonant exchange qubits a simple two-qubit gate is possible
      because in this mode of operation energy conservation suppresses leakage. 

PMID- 23952378
TI  - High-fidelity teleportation of continuous-variable quantum states using
      delocalized single photons.
AB  - Traditional continuous-variable teleportation can only approach unit fidelity in
      the limit of an infinite (and unphysical) amount of squeezing. We describe a new
      method for continuous-variable teleportation that approaches unit fidelity with
      finite resources. The protocol is not based on squeezed states as in traditional
      teleportation but on an ensemble of single photon entangled states. We
      characterize the teleportation scheme with coherent states, mesoscopic
      superposition states, and two-mode squeezed states and we find several situations
      in which near-unity teleportation fidelity can be obtained with modest resources.

PMID- 23952379
TI  - Carnot cycle at finite power: attainability of maximal efficiency.
AB  - We want to understand whether and to what extent the maximal (Carnot) efficiency
      for heat engines can be reached at a finite power. To this end we generalize the
      Carnot cycle so that it is not restricted to slow processes. We show that for
      realistic (i.e., not purposefully designed) engine-bath interactions, the work
      optimal engine performing the generalized cycle close to the maximal efficiency
      has a long cycle time and hence vanishing power. This aspect is shown to relate
      to the theory of computational complexity. A physical manifestation of the same
      effect is Levinthal's paradox in the protein folding problem. The resolution of
      this paradox for realistic proteins allows to construct engines that can extract
      at a finite power 40% of the maximally possible work reaching 90% of the maximal
      efficiency. For purposefully designed engine-bath interactions, the Carnot
      efficiency is achievable at a large power. 

PMID- 23952380
TI  - Kolmogorov-Zakharov spectrum in AdS gravitational collapse.
AB  - We study black hole formation during the gravitational collapse of a massless
      scalar field in asymptotically D-dimensional anti-de Sitter AdS(D) spacetimes for
      D = 4, 5. We conclude that spherically symmetric gravitational collapse in
      asymptotically AdS spaces is turbulent and characterized by a Kolmogorov-Zakharov
      spectrum. Namely, we find that after an initial period of weakly nonlinear
      evolution, there is a regime where the power spectrum of the Ricci scalar evolves
      as omega(-s) with the frequency, omega, and s ~ 1.7 +/- 0.1.

PMID- 23952381
TI  - Time-periodic solutions in an Einstein AdS-massless-scalar-field system.
AB  - We construct time-periodic solutions for a system of a self-gravitating massless
      scalar field, with a negative cosmological constant, in d+1 spacetime dimensions
      at spherical symmetry, both perturbatively and numerically. We estimate the
      convergence radius of the formally obtained perturbative series and argue that it
      is greater then zero. Moreover, this estimate coincides with the boundary of the
      convergence domain of our numerical method and the threshold for the black-hole
      formation. Then we confirm our results with a direct numerical evolution. This
      also gives strong evidence for the nonlinear stability of the constructed time
      periodic solutions. 

PMID- 23952382
TI  - Preheating with nonminimal kinetic terms.
AB  - We present the first (3+1)-dimensional numerical simulations of scalar fields
      with nonminimal kinetic terms. As an example, we examine the existence and
      stability of preheating in the presence of a Dirac-Born-Infeld inflaton coupled
      to a canonical matter field. The simulations represent the full nonlinear theory
      in the presence of an expanding universe. We show that parametric resonance in
      the matter field along with self-resonance in the inflaton repopulate the
      universe with matter particles as efficiently as in traditional preheating. 

PMID- 23952383
TI  - Supersymmetric model for dark matter and baryogenesis motivated by the recent
      CDMS result.
AB  - We discuss a supersymmetric model for cogenesis of dark and baryonic matter where
      the dark matter (DM) has mass in the 8-10 GeV range as indicated by several
      direct detection searches, including most recently the CDMS experiment with the
      desired cross section. The DM candidate is a real scalar field. Two key
      distinguishing features of the model are the following: (i) in contrast with the
      conventional weakly interacting massive particle dark matter scenarios where
      thermal freeze-out is responsible for the observed relic density, our model uses
      nonthermal production of dark matter after reheating of the Universe caused by
      moduli decay at temperatures below the QCD phase transition, a feature which
      alleviates the relic overabundance problem caused by small annihilation cross
      section of light DM particles and (ii) baryogenesis occurs also at similar low
      temperatures from the decay of TeV scale mediator particles arising from moduli
      decay. A possible test of this model is the existence of colored particles with
      TeV masses accessible at the LHC.

PMID- 23952384
TI  - Generation of primordial magnetic fields on linear overdensity scales.
AB  - Magnetic fields appear to be present in all galaxies and galaxy clusters. Recent
      measurements indicate that a weak magnetic field may be present even in the
      smooth low density intergalactic medium. One explanation for these observations
      is that a seed magnetic field was generated by some unknown mechanism early in
      the life of the Universe, and was later amplified by various dynamos in nonlinear
      objects like galaxies and clusters. We show that a primordial magnetic field is
      expected to be generated in the early Universe on purely linear scales through
      vorticity induced by scale-dependent temperature fluctuations, or equivalently, a
      spatially varying speed of sound of the gas. Residual free electrons left over
      after recombination tap into this vorticity to generate magnetic field via the
      Biermann battery process. Although the battery operates even in the absence of
      any relative velocity between dark matter and gas at the time of recombination,
      the presence of such a relative velocity modifies the predicted spatial power
      spectrum of the magnetic field. At redshifts of order a few tens, we estimate a
      root mean square field strength of order 10(-25)-10(-24) G on comoving scales ~10
      kpc. This field, which is generated purely from linear perturbations, is expected
      to be amplified significantly after reionization, and to be further boosted by
      dynamo processes during nonlinear structure formation.

PMID- 23952385
TI  - Spatial modulation and topological current in holographic QCD matter.
AB  - We investigate an impact of the axial-vector interaction on the spatial
      modulation of quark matter. A magnetic field coupled with baryon density leads to
      a topological axial current so that the effect of the axial-vector interaction is
      then crucially enhanced. Using the Sakai-Sugimoto model, we have found that
      contrary to a naive expectation, the spatially modulated phase is less favored
      for a stronger magnetic field, which is realized by the presence of topological
      current. 

PMID- 23952386
TI  - Medium-induced QCD cascade: democratic branching and wave turbulence.
AB  - We study the average properties of the gluon cascade generated by an energetic
      parton propagating through a quark-gluon plasma. We focus on the soft, medium
      induced emissions which control the energy transport at large angles with respect
      to the leading parton. We show that the effect of multiple branchings is
      important. In contrast with what happens in a usual QCD cascade in vacuum, medium
      induced branchings are quasidemocratic, with offspring gluons carrying sizable
      fractions of the energy of their parent gluon. This results in an efficient
      mechanism for the transport of energy toward the medium, which is akin to wave
      turbulence with a scaling spectrum ~1/sqrt[omega]. We argue that the turbulent
      flow may be responsible for the excess energy carried by very soft quanta, as
      revealed by the analysis of the dijet asymmetry observed in Pb-Pb collisions at
      the LHC.

PMID- 23952387
TI  - Chiral plasma instabilities.
AB  - We study the collective modes in relativistic electromagnetic or quark-gluon
      plasmas with an asymmetry between left- and right-handed chiral fermions, based
      on the recently formulated kinetic theory with Berry curvature corrections. We
      find that there exists an unstable mode, signaling the presence of a plasma
      instability. We argue the fate of this "chiral plasma instability" including the
      effect of collisions, and briefly discuss its relevance in heavy ion collisions
      and compact stars. 

PMID- 23952388
TI  - WZ production in association with two jets at next-to-leading order in QCD.
AB  - We report on the calculation of W(+/-) Zjj production with leptonic decays at
      hadron-hadron colliders at next-to-leading order in QCD. These processes are
      important both to test the quartic gauge couplings of the standard model and
      because they constitute relevant backgrounds to beyond standard model physics
      searches. Our results show that the next-to-leading order corrections reduce
      significantly the scale uncertainties and have a nontrivial phase space
      dependence.

PMID- 23952390
TI  - Measurement of the T + T neutron spectrum using the national ignition facility.
AB  - Neutron time-of-flight spectra from inertial confinement fusion experiments with
      tritium-filled targets have been measured at the National Ignition Facility.
      These spectra represent a significant improvement in energy resolution and
      statistics over previous measurements, and afford the first definitive
      observation of a peak resulting from sequential decay through the ground state of
      (5)He at low reaction energies E(c.m.) 100 </~ keV. To describe the spectrum, we
      have developed an R-matrix model that accounts for interferences from fermion
      symmetry and intermediate states, and show these effects to be non-negligible. We
      also find the spectrum can be described by sequential decay through l=1 states in
      (5)He, which differs from previous interpretations.

PMID- 23952391
TI  - Excitation of weakly bound molecules to trilobitelike Rydberg states.
AB  - We observe "trilobitelike" states of ultracold (85)Rb(2) molecules, in which a
      ground-state atom is bound by the electronic wave function of its Rydberg-atom
      partner. We populate these states through the ultraviolet excitation of weakly
      bound molecules, and access a regime of trilobitelike states at low principal
      quantum numbers and with vibrational turning points around 35 Bohr radii. This
      demonstrates that, unlike previous studies that used free-to-bound transitions,
      trilobitelike states can also be excited through bound-to-bound transitions. This
      approach provides high excitation probabilities without requiring high-density
      samples, and affords the ability to control the excitation radius by selection of
      the initial-state vibrational level.

PMID- 23952392
TI  - Decay rate measurement of the first vibrationally excited state of MgH+ in a
      cryogenic Paul trap.
AB  - We present a method to measure the decay rate of the first excited vibrational
      state of polar molecular ions that are part of a Coulomb crystal in a cryogenic
      linear Paul trap. Specifically, we have monitored the decay of the |nu = 1, J =
      1)(X) towards the |nu = 0, J = 0)(X) level in MgH+ by saturated laser excitation
      of the |nu = 0, J = 2)(X)-|nu = 1, J = 1)(X) transition followed by state
      selective resonance enhanced two-photon dissociation out of the |nu = 0, J=2)(X)
      level. The experimentally observed rate of 6.32(0.69) s(-1) is in excellent
      agreement with the theory value of 6.13(0.03) s(-1) (this Letter). The technique
      enables the determination of decay rates, and thus absorption strengths, with an
      accuracy at the few percent level.

PMID- 23952393
TI  - Quantum quench in an atomic one-dimensional Ising chain.
AB  - We study nonequilibrium dynamics for an ensemble of tilted one-dimensional atomic
      Bose-Hubbard chains after a sudden quench to the vicinity of the transition point
      of the Ising paramagnetic to antiferromagnetic quantum phase transition. The
      quench results in coherent oscillations for the orientation of effective Ising
      spins, detected via oscillations in the number of doubly occupied lattice sites.
      We characterize the quench by varying the system parameters. We report
      significant modification of the tunneling rate induced by interactions and show
      clear evidence for collective effects in the oscillatory response. 

PMID- 23952394
TI  - Magic frequencies in atom-light interaction for precision probing of the density
      matrix.
AB  - We analyze theoretically and experimentally the existence of a magic frequency
      for which the absorption of a linearly polarized light beam by a vapor of alkali
      metal atoms is independent of the population distribution among the Zeeman
      sublevels and the angle between the beam and a magnetic field. The phenomenon
      originates from a peculiar cancellation of the contributions of higher moments of
      the atomic density matrix, and is described using the Wigner-Eckart theorem and
      inherent properties of Clebsch-Gordan coefficients. One important application is
      the robust measurement of the hyperfine population. 

PMID- 23952395
TI  - Quantum tunneling of oxygen atoms on very cold surfaces.
AB  - Any evolving system can change state via thermal mechanisms (hopping a barrier)
      or via quantum tunneling. Most of the time, efficient classical mechanisms
      dominate at high temperatures. This is why an increase of the temperature can
      initiate the chemistry. We present here an experimental investigation of O-atom
      diffusion and reactivity on water ice. We explore the 6-25 K temperature range at
      submonolayer surface coverages. We derive the diffusion temperature law and
      observe the transition from quantum to classical diffusion. Despite the high mass
      of O, quantum tunneling is efficient even at 6 K. As a consequence, the solid
      state astrochemistry of cold regions should be reconsidered and should include
      the possibility of forming larger organic molecules than previously expected.

PMID- 23952396
TI  - Test of the universality of the three-body Efimov parameter at narrow Feshbach
      resonances.
AB  - We measure the critical scattering length for the appearance of the first three
      body bound state, or Efimov three-body parameter, at seven different Feshbach
      resonances in ultracold ^{39}K atoms. We study both intermediate and narrow
      resonances, where the three-body spectrum is expected to be determined by the
      nonuniversal coupling of two scattering channels. Instead, our observed ratio of
      the three-body parameter with the van der Waals radius is approximately the same
      universal ratio as for broader resonances. This unexpected observation suggests
      the presence of a new regime for three-body scattering at narrow resonances.

PMID- 23952397
TI  - Giant cross-Kerr effect for propagating microwaves induced by an artificial atom.
AB  - We investigate the effective interaction between two microwave fields, mediated
      by a transmon-type superconducting artificial atom which is strongly coupled to a
      coplanar transmission line. The interaction between the fields and atom produces
      an effective cross-Kerr coupling. We demonstrate average cross-Kerr phase shifts
      of up to 20 degrees per photon with both coherent microwave fields at the single
      photon level. Our results provide an important step toward quantum applications
      with propagating microwave photons.

PMID- 23952398
TI  - Nonlinear interaction effects in a strongly driven optomechanical cavity.
AB  - We consider how nonlinear interaction effects can manifest themselves and even be
      enhanced in a strongly driven optomechanical system. Using a Keldysh Green's
      function approach, we calculate modifications to the cavity density of states due
      to both linear and nonlinear optomechanical interactions, showing that strong
      modifications can arise even for a weak nonlinear interaction. We show how this
      quantity can be directly probed in an optomechanically induced transparency-type
      experiment. We also show how the enhanced interaction can lead to nonclassical
      behavior, as evidenced by the behavior of g(2) correlation functions.

PMID- 23952399
TI  - Signatures of nonlinear cavity optomechanics in the weak coupling regime.
AB  - We identify signatures of the intrinsic nonlinear interaction between light and
      mechanical motion in cavity optomechanical systems. These signatures are
      observable even when the cavity linewidth exceeds the optomechanical coupling
      rate. A strong laser drive red detuned by twice the mechanical frequency from the
      cavity resonance frequency makes two-phonon processes resonant, which leads to a
      nonlinear version of optomechanically induced transparency. This effect provides
      a new method of measuring the average phonon number of the mechanical oscillator.
      Furthermore, we show that if the strong laser drive is detuned by half the
      mechanical frequency, optomechanically induced transparency also occurs due to
      resonant two-photon processes. The cavity response to a second probe drive is in
      this case nonlinear in the probe power. These effects should be observable with
      optomechanical coupling strengths that have already been realized in experiments.

PMID- 23952389
TI  - Measurement of J/psi azimuthal anisotropy in Au+Au collisions at sqrt[s(NN)]=200
      GeV.
AB  - The measurement of J/psi azimuthal anisotropy is presented as a function of
      transverse momentum for different centralities in Au+Au collisions at
      sqrt[s(NN)]=200 GeV. The measured J/psi elliptic flow is consistent with zero
      within errors for transverse momentum between 2 and 10 GeV/c. Our measurement
      suggests that J/psi particles with relatively large transverse momenta are not
      dominantly produced by coalescence from thermalized charm quarks, when comparing
      to model calculations.

PMID- 23952400
TI  - Strong coupling to two-dimensional Anderson localized modes.
AB  - We use a scattering formalism to derive a condition of strong coupling between a
      resonant scatterer and an Anderson localized mode for electromagnetic waves in
      two dimensions. The strong coupling regime is demonstrated based on exact
      numerical simulations, in perfect agreement with theory. The strong coupling
      threshold can be expressed in terms of the Thouless conductance and the Purcell
      factor. This connects key concepts in transport theory and cavity quantum
      electrodynamics, and provides a practical tool for the design or analysis of
      experiments. 

PMID- 23952401
TI  - Nanometric resolution with far-field optical profilometry.
AB  - We show experimentally that a resolution far beyond that of conventional far
      field optical profilometers can be reached with optical diffraction tomography.
      This result is obtained in the presence of multiple scattering when using an
      adapted inverse scattering algorithm for profile reconstruction. This new
      profilometry technique, whose resolution can be compared to that of atomic
      microscopes, also gives access to the permittivity of the surface. 

PMID- 23952402
TI  - Nonlinear stage of modulation instability.
AB  - We study the nonlinear stage of the modulation instability of a condensate in the
      framework of the focusing nonlinear Schrodinger equation (NLSE). We find a
      general N-solitonic solution of the focusing NLSE in the presence of a condensate
      by using the dressing method. We separate a special designated class of "regular
      solitonic solutions" that do not disturb phases of the condensate at infinity by
      coordinate. All regular solitonic solutions can be treated as localized
      perturbations of the condensate. We find an important class of "superregular
      solitonic solutions" which are small perturbations at a certain moment of time.
      They describe the nonlinear stage of the modulation instability of the
      condensate. 

PMID- 23952403
TI  - Causal and structural connectivity of pulse-coupled nonlinear networks.
AB  - We study the reconstruction of structural connectivity for a general class of
      pulse-coupled nonlinear networks and show that the reconstruction can be
      successfully achieved through linear Granger causality (GC) analysis. Using spike
      triggered correlation of whitened signals, we obtain a quadratic relationship
      between GC and the network couplings, thus establishing a direct link between the
      causal connectivity and the structural connectivity within these networks. Our
      work may provide insight into the applicability of GC in the study of the
      function of general nonlinear networks. 

PMID- 23952404
TI  - Virtual chimera states for delayed-feedback systems.
AB  - Time-delayed systems are found to display remarkable temporal patterns the
      dynamics of which split into regular and chaotic components repeating at the
      interval of a delay. This novel long-term behavior for delay dynamics results
      from strongly asymmetric nonlinear delayed feedback driving a highly damped
      harmonic oscillator dynamics. In the corresponding virtual space-time
      representation, the behavior is found to develop as a chimeralike state, a new
      paradigmatic object from the network theory characterized by the coexistence of
      synchronous and incoherent oscillations. Numerous virtual chimera states are
      obtained and analyzed, through experiment, theory, and simulations. 

PMID- 23952405
TI  - Hydrodynamic supercontinuum.
AB  - We report the experimental observation of multi-bound-soliton solutions of the
      nonlinear Schrodinger equation (NLS) in the context of hydrodynamic surface
      gravity waves. Higher-order N-soliton solutions with N=2, 3 are studied in detail
      and shown to be associated with self-focusing in the wave group dynamics and the
      generation of a steep localized carrier wave underneath the group envelope. We
      also show that for larger input soliton numbers, the wave group experiences
      irreversible spectral broadening, which we refer to as a hydrodynamic
      supercontinuum by analogy with optics. This process is shown to be associated
      with the fission of the initial multisoliton into individual fundamental solitons
      due to higher-order nonlinear perturbations to the NLS. Numerical simulations
      using an extended NLS model described by the modified nonlinear Schrodinger
      equation, show excellent agreement with experiment and highlight the universal
      role that higher-order nonlinear perturbations to the NLS play in supercontinuum
      generation. 

PMID- 23952406
TI  - Crackling versus continuumlike dynamics in brittle failure.
AB  - We study how the loading rate, specimen geometry, and microstructural texture
      select the dynamics of a crack moving through an heterogeneous elastic material
      in the quasistatic approximation. We find a transition, fully controlled by two
      dimensionless variables, between dynamics ruled by continuum fracture mechanics
      and crackling dynamics. Selection of the latter by the loading, microstructure,
      and specimen parameters is formulated in terms of scaling laws on the power
      spectrum of crack velocity. This analysis defines the experimental conditions
      required to observe crackling in fracture. Beyond failure problems, the results
      extend to a variety of situations described by models of the same universality
      class, e.g., the dynamics in wetting or of domain walls in amorphous
      ferromagnets. 

PMID- 23952407
TI  - Transition from wave turbulence to dynamical crumpling in vibrated elastic
      plates.
AB  - We study the dynamical regime of wave turbulence of a vibrated thin elastic plate
      based on experimental and numerical observations. We focus our study on the
      strongly nonlinear regime described in a previous Letter by Yokoyama and Takaoka.
      At small forcing, a weakly nonlinear regime is compatible with the weak
      turbulence theory when the dissipation is localized at high wave number. When the
      forcing intensity is increased, a strongly nonlinear regime emerges: singular
      structures dominate the dynamics at large scales whereas at small scales the weak
      turbulence is still present. A turbulence of singular structures with folds and D
      cones develops that alters significantly the energy spectra and causes the
      emergence of intermittency. 

PMID- 23952408
TI  - Analytical results for front pinning between an hexagonal pattern and a uniform
      state in pattern-formation systems.
AB  - In pattern-forming systems, localized patterns are states of intermediate
      complexity between fully extended ordered patterns and completely irregular
      patterns. They are formed by stationary fronts enclosing an ordered pattern
      inside an homogeneous background. In two dimensions, the ordered pattern is most
      often hexagonal and the conditions for fronts to stabilize are still unknown. In
      this Letter, we show how the locking of these fronts depends on their orientation
      relative to the pattern. The theory rests on general asymptotic arguments valid
      when the spatial scale of the front is slow compared to that of the hexagonal
      pattern. Our analytical results are confirmed by numerical simulations with the
      Swift-Hohenberg equation, relevant to hydrodynamical and buckling instabilities,
      and a nonlinear optical cavity model. 

PMID- 23952409
TI  - Suppression of microbunching instability using bending magnets in free-electron
      laser linacs.
AB  - The microbunching instability driven by collective effects of the beam inside an
      accelerator can significantly degrade the final electron beam quality for free
      electron laser (FEL) radiation. In this Letter, we propose an inexpensive scheme
      to suppress such an instability in accelerators for next generation FEL light
      sources. Instead of using an expensive device such as a laser heater or RF
      deflecting cavities, this scheme uses longitudinal mixing associated with the
      transverse spread of the beam through bending magnets inside the accelerator
      transport system to suppress the instability. The final uncorrelated energy
      spread increases roughly by the current compression factor, which is important in
      seeded FEL schemes in order to achieve high harmonic short-wavelength x-ray
      radiation. 

PMID- 23952410
TI  - Stochasticity effects in quantum radiation reaction.
AB  - When an ultrarelativistic electron beam collides with a sufficiently intense
      laser pulse, radiation-reaction effects can strongly alter the beam dynamics. In
      the realm of classical electrodynamics, radiation reaction has a beneficial
      effect on the electron beam as it tends to reduce its energy spread. Here we show
      that when quantum effects become important, radiation reaction induces the
      opposite effect; i.e., the energy distribution of the electron beam spreads out
      after interacting with the laser pulse. We identify the physical origin of this
      opposite tendency in the intrinsic stochasticity of photon emission, which
      becomes substantial in the quantum regime. Our numerical simulations indicate
      that the predicted effects of the stochasticity can be measured already with
      presently available lasers and electron accelerators. 

PMID- 23952411
TI  - Temperature measurements of fusion plasmas produced by Petawatt-Laser-Irradiated
      D2 - (3)He or CD4 - (3)He clustering gases.
AB  - Two different methods have been employed to determine the plasma temperature in a
      laser-cluster fusion experiment on the Texas Petawatt laser. In the first, the
      temperature was derived from time-of-flight data of deuterium ions ejected from
      exploding D(2) or CD(4) clusters. In the second, the temperature was measured
      from the ratio of the rates of two different nuclear fusion reactions occurring
      in the plasma at the same time: D(d,(3)He)n and (3)He(d,p)(4)He. The temperatures
      determined by these two methods agree well, which indicates that (i) the ion
      energy distribution is not significantly distorted when ions travel in the
      disassembling plasma; (ii) the kinetic energy of deuterium ions, especially the
      "hottest part" responsible for nuclear fusion, is well described by a near
      Maxwellian distribution.

PMID- 23952412
TI  - Minimally constrained model of self-organized helical states in reversed-field
      pinches.
AB  - We show that the self-organized single-helical-axis (SHAx) and double-axis (DAx)
      states in reversed field pinches can be reproduced in a minimally constrained
      equilibrium model using only five parameters. This is a significant reduction on
      previous representations of the SHAx which have required an infinite number of
      constraints. The DAx state, which has a nontrivial topology, has not previously
      been reproduced using an equilibrium model that preserves this topological
      structure. We show that both states are a consequence of transport barrier
      formation in the plasma core, in agreement with experimental results. We take the
      limit of zero pressure in this work, although the model is also valid for finite
      pressure. 

PMID- 23952413
TI  - Amplification of ultrashort laser pulses by brillouin backscattering in plasmas.
AB  - Plasma media, by exciting Raman (electron) or Brillouin (ion) waves, have been
      used to transfer energy from moderately long, high-energy light pulses to short
      ones. Using multidimensional kinetic simulations, we define here the optimum
      window in which a Brillouin scheme can be exploited for amplification and
      compression of short laser pulses over short distances to very high power. We
      also show that shaping the plasma allows for increasing the efficiency of the
      process while minimizing other unwanted plasma processes. Moreover, we show that,
      contrary to what was traditionally thought (i.e., using Brillouin in gases for
      nanosecond pulse compression), this scheme is able to amplify pulses of extremely
      short duration. 

PMID- 23952414
TI  - Intrinsic rotation driven by non-Maxwellian equilibria in Tokamak plasmas.
AB  - The effect of small deviations from a Maxwellian equilibrium on turbulent
      momentum transport in tokamak plasmas is considered. These non-Maxwellian
      features, arising from diamagnetic effects, introduce a strong dependence of the
      radial flux of cocurrent toroidal angular momentum on collisionality: As the
      plasma goes from nearly collisionless to weakly collisional, the flux reverses
      direction from radially inward to outward. This indicates a collisionality
      dependent transition from peaked to hollow rotation profiles, consistent with
      experimental observations of intrinsic rotation. 

PMID- 23952415
TI  - Planck distribution of phonons in a Bose-Einstein condensate.
AB  - The Planck distribution of photons emitted by a blackbody led to the development
      of quantum theory. An analogous distribution of phonons should exist in a Bose
      Einstein condensate. We observe this Planck distribution of thermal phonons in a
      3D condensate. This observation provides an important confirmation of the basic
      nature of the condensate's quantized excitations. In contrast to the bunching
      effect, the density fluctuations are seen to increase with increasing
      temperature. This is due to the nonconservation of the number of phonons. In the
      case of rapid cooling, the phonon temperature is out of equilibrium with the
      surrounding thermal cloud. In this case, a Bose-Einstein condensate is not as
      cold as previously thought. These measurements are enabled by our in situ k-space
      technique.

PMID- 23952416
TI  - Extraordinary sound transmission through density-near-zero ultranarrow channels.
AB  - We introduce the acoustic equivalent of "supercoupling" by studying the anomalous
      sound transmission and uniform energy squeezing through ultranarrow acoustic
      channels filled with zero-density metamaterials. As a realistic example, we
      propose their realization by inserting transverse membranes with a subwavelength
      period along the channel, and we prove a novel form of acoustic tunneling based
      on impedance matching and infinite phase velocity at the zero-density operation.
      We envision applications in sensing, noise control, cloaking, and energy
      harvesting. 

PMID- 23952417
TI  - Origin of the bismuth-induced decohesion of nickel and copper grain boundaries.
AB  - Ductile metals such as Ni and Cu can become brittle when certain impurities
      (e.g., Bi) diffuse and segregate into their grain boundaries (GBs). Using first
      principles calculations, we investigate the microscopic origin of the Bi-induced
      loss of cohesion of Ni and Cu GBs. We find that the Bi bilayer interfacial phase
      is the most stable impurity phase under the Bi-rich condition, while the Bi
      monolayer phase is a metastable phase regardless of the value of the Bi chemical
      potential. Our finding is consistent with the recent experimental observation for
      Ni GBs [Luo et al. Science 333, 1730 (2011)]. The electric polarization effect of
      the Bi bilayer substantially enhances the strength of the Bi-metal interfacial
      bonds, stabilizing the bilayer phase over other phases. The Bi-Bi interlayer
      bonding is significantly weakened in the GBs, leading to a factor of 20 to 50
      decrease in the GB cohesion, which has strong implications for the understanding
      of Bi-induced intergranular fracture of Ni and Cu polycrystals.

PMID- 23952418
TI  - Effects of density conservation and hydrodynamics on aging in nonequilibrium
      processes.
AB  - Aging in kinetics of three different phase transitions, viz., magnetic, a binary
      solid, and a single component fluid, are studied via Monte Carlo and molecular
      dynamics simulations in three space dimensions with the objective of identifying
      the effects of order-parameter conservation and hydrodynamics. We observe that
      the relevant autocorrelations exhibit power-law decay in a ferromagnet and binary
      solid but with different exponents. At early time the fluid autocorrelation
      function nicely follows that of the binary solid, the order parameter being
      conserved for both of them, as opposed to a ferromagnet. At a late time the fluid
      data crosses over to an exponential decay which we identify as a hydrodynamic
      effect and we provide analytical justification for this behavior.

PMID- 23952419
TI  - Nonequilibrium critical Casimir effect in binary fluids.
AB  - Colloids immersed in a critical binary liquid mixture are subject to critical
      Casimir forces (CCFs) because they confine its concentration fluctuations and
      influence the latter via effective surface fields. To date, CCFs have been
      primarily studied in thermodynamic equilibrium. However, due to the critical
      slowing down, the order parameter around a particle can easily be perturbed by
      any motion of the colloid or by solvent flow. This leads to significant but
      largely unexplored changes in the CCF. Here we study the drag force on a single
      colloidal particle moving in a near-critical fluid mixture and the relative
      motion of two colloids due to the CCF acting on them. In order to account for the
      kinetic couplings among the order parameter field, the solvent velocity field,
      and the particle motion, we use a fluid particle dynamics method. These studies
      extend the understanding of CCFs from thermal equilibrium to nonequilibrium
      processes, which are relevant to current experiments, and show the emergence of
      significant effects near the critical point. 

PMID- 23952420
TI  - Light-induced crystallization of cold atoms in a 1D optical trap.
AB  - Collective off-resonant scattering of coherent light by a cold gas induces long
      range interactions via interference of light scattered by different particles. In
      a 1D configuration, these interactions grow particularly strong by coupling the
      particles via an optical nanofiber. Above a threshold pump laser intensity, we
      predict a phase transition from a homogeneous density to a self-sustained
      crystalline order. In the dispersive regime, we determine the critical condition
      for the onset of order as well as the forms of gas density and electric field
      patterns above threshold. Surprisingly, there can coexist multiple ordered states
      with distinct appearances. 

PMID- 23952421
TI  - Strain-induced defect superstructure on the SrTiO3(110) surface.
AB  - We report on a combined scanning tunneling microscopy and density functional
      theory calculation study of the SrTiO(3) (110)-(4 * 1) surface. It is found that
      antiphase domains are formed along the [11[over -]0]-oriented stripes on the
      surface. The domain boundaries are decorated by defect pairs consisting of
      Ti(2)O(3) vacancies and Sr adatoms, which relieve the residual stress. The
      formation energy of and interactions between vacancies result in a defect
      superstructure. It is suggested that the density and distributions of defects can
      be tuned by strain engineering, providing a flexible platform for the designed
      growth of complex oxide materials.

PMID- 23952422
TI  - Dynamical Jahn-Teller effect and antiferromagnetism in Cs3C60.
AB  - The dynamical Jahn-Teller effect on fullerene sites in insulating Cs(3)C(60) is
      investigated fully ab initio. The vibronic excitations of rotational type are at
      >= 65 cm(-1), while the net kinetic contribution to the Jahn-Teller stabilization
      energy constitutes approximately 90 meV. This means that no localization of
      distortions by intermolecular interactions is possible in these fullerides;
      therefore, free rotations of deformations take place independently on each C(60).
      The latter destroy the orbital ordering and establish a conventional exchange
      interaction between S = 1/2 on fullerene sites. The corresponding exchange model
      is derived and predicts the Neel temperature for A15 Cs(3)C(60) close to
      experiment.

PMID- 23952423
TI  - Time-reversal-invariant topological superconductivity and Majorana Kramers pairs.
AB  - We propose a feasible route to engineer one- and two-dimensional time-reversal
      invariant topological superconductors (SCs) via proximity effects between
      nodeless s(+/-) wave iron-based SCs and semiconductors with large Rashba spin
      orbit interactions. At the boundary of a time-reversal-invariant topological SC,
      there emerges a Kramers pair of Majorana edge (bound) states. For a Josephson pi
      junction, we predict a Majorana quartet that is protected by mirror symmetry and
      leads to a mirror fractional Josephson effect. We analyze the evolution of the
      Majorana pair in Zeeman fields, as the SC undergoes a symmetry class change as
      well as topological phase transitions, providing an experimental signature in
      tunneling spectroscopy. We briefly discuss the realization of this mechanism in
      candidate materials and the possibility of using s and d wave SCs and weak
      topological insulators.

PMID- 23952424
TI  - Topological mirror superconductivity.
AB  - We demonstrate the existence of topological superconductors (SCs) protected by
      mirror and time-reversal symmetries. D-dimensional (D=1, 2, 3) crystalline SCs
      are characterized by 2(D-1) independent integer topological invariants, which
      take the form of mirror Berry phases. These invariants determine the distribution
      of Majorana modes on a mirror symmetric boundary. The parity of total mirror
      Berry phase is the Z(2) index of a class DIII SC, implying that a DIII
      topological SC with a mirror line must also be a topological mirror SC but not
      vice versa and that a DIII SC with a mirror plane is always time-reversal trivial
      but can be mirror topological. We introduce representative models and suggest
      experimental signatures in feasible systems. Advances in quantum computing, the
      case for nodal SCs, the case for class D, and topological SCs protected by
      rotational symmetries are pointed out.

PMID- 23952425
TI  - Role of oxygen holes in Li(x)CoO(2) revealed by soft X-ray spectroscopy.
AB  - The fundamental electronic structure of the widely used battery material
      Li(x)CoO(2) still remains a mystery. Soft x-ray absorption spectroscopy of
      Li(x)CoO(2) reveals that holes with strong O 2p character play an essential role
      in the electronic conductivity of the Co(3+)/Co(4+) mixed valence CoO(2) layer.
      The oxygen holes are bound to the Co(4+) sites and the Li-ion vacancy, suggesting
      that the Li-ion flow can be stabilized by oxygen hole back flow. Such an oxygen
      hole state of Li(x)CoO(2) is unique among the various oxide-based battery
      materials and is one of the key ingredients to improving their electronic and Li
      ion conductivities.

PMID- 23952426
TI  - Extremely large magnetoresistance in the nonmagnetic metal PdCoO2.
AB  - Extremely large magnetoresistance is realized in the nonmagnetic layered metal
      PdCoO(2). In spite of a highly conducting metallic behavior with a simple quasi
      two-dimensional hexagonal Fermi surface, the interlayer resistance reaches up to
      35,000% for the field along the [11[over -]0] direction. Furthermore, the
      temperature dependence of the resistance becomes nonmetallic for this field
      direction, while it remains metallic for fields along the [110] direction. Such
      severe and anisotropic destruction of the interlayer coherence by a magnetic
      field on a simple Fermi surface is ascribable to orbital motion of carriers on
      the Fermi surface driven by the Lorentz force, but seems to have been largely
      overlooked until now.

PMID- 23952427
TI  - Monte Carlo study of the semimetal-insulator phase transition in monolayer
      graphene with a realistic interelectron interaction potential.
AB  - We report on the results of the first-principles numerical study of spontaneous
      breaking of chiral (sublattice) symmetry in suspended monolayer graphene due to
      electrostatic interaction, which takes into account the screening of Coulomb
      potential by electrons on sigma orbitals. In contrast to the results of previous
      numerical simulations with unscreened potential, we find that suspended graphene
      is in the conducting phase with unbroken chiral symmetry. This finding is in
      agreement with recent experimental results by the Manchester group [D. C. Elias
      et al., Nat. Phys. 7, 701 (2011); A. S. Mayorov et al., Nano Lett. 12, 4629
      (2012)]. Further, by artificially increasing the interaction strength, we
      demonstrate that suspended graphene is quite close to the phase transition
      associated with spontaneous chiral symmetry breaking, which suggests that
      fluctuations of chirality and nonperturbative effects might still be quite
      important.

PMID- 23952428
TI  - Correlations between Majorana fermions through a superconductor.
AB  - We consider a model of ballistic quasi-one-dimensional semiconducting wire with
      intrinsic spin-orbit interaction placed on the surface of a bulk s-wave
      superconductor (SC), in the presence of an external magnetic field. This setup
      has been shown to give rise to a topological superconducting state in the wire,
      characterized by a pair of Majorana-fermion (MF) bound states formed at the two
      ends of the wire. Here, we demonstrate that besides the well-known direct-overlap
      induced energy splitting, the two MF bound states may hybridize via elastic
      tunneling processes through virtual quasiparticle states in the SC, giving rise
      to an additional energy splitting between MF states from the same as well as from
      different wires. 

PMID- 23952429
TI  - Electric-field tuning of the surface band structure of topological insulator
      Sb2Te3 thin films.
AB  - We measured the response of the surface state spectrum of epitaxial Sb(2)Te(3)
      thin films to applied gate electric fields by low temperature scanning tunneling
      microscopy. The gate dependent shift of the Fermi level and the screening effect
      from bulk carriers vary as a function of film thickness. We observed a gap
      opening at the Dirac point for films thinner than four quintuple layers, due to
      the coupling of the top and bottom surfaces. Moreover, the top surface state band
      gap of the three quintuple layer films was found to be tunable by a back gate,
      indicating the possibility of observing a topological phase transition in this
      system. Our results are well explained by an effective model of 3D topological
      insulator thin films with structure inversion asymmetry, indicating that three
      quintuple layer Sb(2)Te(3) films are topologically nontrivial and belong to the
      quantum spin Hall insulator class.

PMID- 23952430
TI  - Mapping image potential states on graphene quantum dots.
AB  - Free-electron-like image potential states are observed in scanning tunneling
      spectroscopy on graphene quantum dots on Ir(111) acting as potential wells. The
      spectrum strongly depends on the size of the nanostructure as well as on the
      spatial position on top, indicating lateral confinement. Analysis of the
      substructure of the first state by the spatial mapping of the constant energy
      local density of states reveals characteristic patterns of confined states. The
      most pronounced state is not the ground state, but an excited state with a
      favorable combination of the local density of states and parallel momentum
      transfer in the tunneling process. Chemical gating tunes the confining potential
      by changing the local work function. Our experimental determination of this work
      function allows us to deduce the associated shift of the Dirac point. 

PMID- 23952431
TI  - How many quantum phase transitions exist inside the superconducting dome of the
      iron pnictides?
AB  - Recent experiments on two iron-pnictide families suggest the existence of a
      single quantum phase transition inside the superconducting dome despite the fact
      that two separate transition lines--magnetic and nematic-cross the
      superconducting dome at T(c). Here we argue that these two observations are
      actually consistent. We show, using a microscopic model, that each order coexists
      with superconductivity for a wide range of parameters, and both transition lines
      continue into the superconducting dome below T(c). However, at some
      T(merge)<T(c), the two transitions merge and continue down to T=0 as a single
      simultaneous first-order nematic-magnetic transition. We show that
      superconductivity has a profound effect on the character of this first-order
      transition, rendering it weakly first order and allowing strong fluctuations to
      exist near the quantum phase transition.

PMID- 23952432
TI  - Higgs amplitude mode in the BCS superconductors Nb1-xTi(x)N induced by terahertz
      pulse excitation.
AB  - Ultrafast responses of BCS superconductor Nb(1-x)Ti(x)N films in a nonadiabatic
      excitation regime were investigated by using terahertz (THz) pump-THz probe
      spectroscopy. After an instantaneous excitation with the monocycle THz pump
      pulse, a transient oscillation emerges in the electromagnetic response in the BCS
      gap energy region. The oscillation frequency coincides with the asymptotic value
      of the BCS gap energy, indicating the appearance of the theoretically anticipated
      collective amplitude mode of the order parameter, namely the Higgs amplitude
      mode. Our result opens a new pathway to the ultrafast manipulation of the
      superconducting order parameter by optical means.

PMID- 23952433
TI  - Orbital nematic instability in the two-orbital Hubbard model: renormalization
      group + constrained RPA analysis.
AB  - Motivated by the nematic electronic fluid phase in Sr(3)Ru(2)O(7), we develop a
      combined scheme of the renormalization-group method and the random-phase
      approximation-type method, and analyze orbital susceptibilities of the (d(xz),
      d(yz))-orbital Hubbard model with high accuracy. It is confirmed that the present
      model exhibits a ferro-orbital instability near the magnetic or superconducting
      quantum criticality, due to the Aslamazov-Larkin-type vertex corrections. This
      mechanism of orbital nematic order presents a natural explanation for the nematic
      order in Sr(3)Ru(2)O(7), and is expected to be realized in various multiorbital
      systems, such as Fe-based superconductors.

PMID- 23952434
TI  - Phase retrapping in a pointlike phi Josephson junction: the butterfly effect.
AB  - We consider a phi Josephson junction, which has a bistable zero-voltage state
      with the stationary phases psi = +/-phi. In the nonzero voltage state the phase
      "moves" viscously along a tilted periodic double-well potential. When the tilting
      is reduced quasistatically, the phase is retrapped in one of the potential wells.
      We study the viscous phase dynamics to determine in which well (-phi or +phi) the
      phase is retrapped for a given damping, when the junction returns from the finite
      voltage state back to the zero-voltage state. In the limit of low damping, the
      phi Josephson junction exhibits a butterfly effect-extreme sensitivity of the
      destination well on damping. This leads to an impossibility to predict the
      destination well.

PMID- 23952435
TI  - Two-dimensional superconducting state of monolayer Pb films grown on GaAs(110) in
      a strong parallel magnetic field.
AB  - Two-dimensional (2D) superconductivity was studied by magnetotransport
      measurements on single-atomic-layer Pb films on a cleaved GaAs(110) surface. The
      superconducting transition temperature shows only a weak dependence on the
      parallel magnetic field up to 14T, which is higher than the Pauli paramagnetic
      limit. Furthermore, the perpendicular-magnetic-field dependence of the sheet
      resistance is almost independent of the presence of the parallel field component.
      These results are explained in terms of an inhomogeneous superconducting state
      predicted for 2D metals with a large Rashba spin splitting.

PMID- 23952436
TI  - Development of density-functional theory for a plasmon-assisted superconducting
      state: application to lithium under high pressures.
AB  - We extend the density-functional theory for superconductors (SCDFT) to take
      account of the dynamical structure of the screened Coulomb interaction. We
      construct an exchange-correlation kernel in the SCDFT gap equation on the basis
      of the random-phase approximation, where electronic collective excitations such
      as plasmons are properly treated. Through an application to fcc lithium under
      high pressures, we demonstrate that our new kernel gives higher transition
      temperatures (T(c)) when the plasmon and phonon cooperatively mediate pairing and
      it improves the agreement between the calculated and experimentally observed
      T(c). The present formalism opens the door to nonempirical studies on
      unconventional electron mechanisms of superconductivity based on density
      functional theory.

PMID- 23952437
TI  - Pauli-limited multiband superconductivity in KFe2As2.
AB  - The upper critical field H(c2)(T) of the multiband superconductor KFe2As2 has
      been studied via low-temperature thermal expansion and magnetostriction
      measurements. We present compelling evidence for Pauli-limiting effects
      dominating H(c2)(T) for H || a, as revealed by a crossover from second- to first
      order phase transitions to the superconducting state in the magnetostriction
      measurements down to 50 mK. Corresponding features were absent for H || c. To our
      knowledge, this crossover constitutes the first confirmation of Pauli limiting of
      the H(c2)(T) of a multiband superconductor. The results are supported by modeling
      Pauli limits for single-band and multiband cases.

PMID- 23952438
TI  - Quantum interference oscillations of the superparamagnetic blocking in an Fe8
      molecular nanomagnet.
AB  - We show that the dynamic magnetic susceptibility and the superparamagnetic
      blocking temperature of an Fe(8) single molecule magnet oscillate as a function
      of the magnetic field H(x) applied along its hard magnetic axis. These
      oscillations are associated with quantum interferences, tuned by H(x), between
      different spin tunneling paths linking two excited magnetic states. The
      oscillation period is determined by the quantum mixing between the ground S=10
      and excited multiplets. These experiments enable us to quantify such mixing. We
      find that the weight of excited multiplets in the magnetic ground state of Fe(8)
      amounts to approximately 11.6%.

PMID- 23952439
TI  - Ferromagnetic exchange anisotropy from antiferromagnetic superexchange in the
      mixed 3d-5d transition-metal compound Sr3CuIrO6.
AB  - We report a combined experimental and theoretical study of the unusual
      ferromagnetism in the one-dimensional copper-iridium oxide Sr(3)CuIrO(6).
      Utilizing Ir L(3) edge resonant inelastic x-ray scattering, we reveal a large gap
      magnetic excitation spectrum. We find that it is caused by an unusual exchange
      anisotropy generating mechanism, namely, strong ferromagnetic anisotropy arising
      from antiferromagnetic superexchange, driven by the alternating strong and weak
      spin-orbit coupling on the 5d Ir and 3d Cu magnetic ions, respectively. From
      symmetry consideration, this novel mechanism is generally present in systems with
      edge-sharing Cu(2+)O(4) plaquettes and Ir(4+)O(6) octahedra. Our results point to
      unusual magnetic behavior to be expected in mixed 3d-5d transition-metal
      compounds via exchange pathways that are absent in pure 3d or 5d compounds.

PMID- 23952440
TI  - Families of quasilocal conservation laws and quantum spin transport.
AB  - For fundamental integrable quantum chains with deformed symmetries we outline a
      general procedure for defining a continuous family of quasilocal operators whose
      time derivative is supported near the two boundary sites only. The program is
      implemented for a spin 1/2 XXZ chain, resulting in improved rigorous estimates
      for the high temperature spin Drude weight. 

PMID- 23952441
TI  - Direct observation of thermal relaxation in artificial spin ice.
AB  - We study the thermal relaxation of artificial spin ice with photoemission
      electron microscopy, and are able to directly observe how such a system finds its
      way from an energetically excited state to the ground state. On plotting vertex
      type populations as a function of time, we can characterize the relaxation, which
      occurs in two stages, namely a string and a domain regime. Kinetic Monte Carlo
      simulations agree well with the temporal evolution of the magnetic state when
      including disorder, and the experimental results can be explained by considering
      the effective interaction energy associated with the separation of pairs of
      vertex excitations. 

PMID- 23952442
TI  - Measurement of an exciton Rabi rotation in a single GaN/Al(x)Ga(1-x)N nanowire
      quantum dot using photoluminescence spectroscopy: evidence for coherent control.
AB  - Experimental observation of excited state exciton Rabi rotation in a single GaN
      quantum dot is presented. The dot is embedded in a site-controlled GaN/AlGaN
      nanowire. Damped oscillation is observed in the power-dependent spectra of the
      quantum-dot ground state upon resonant pumping of an excited state that had been
      identified by photoluminescence excitation spectroscopy. A discussion on the
      origins of the damping is given. 

PMID- 23952443
TI  - Measurement of two low-temperature energy gaps in the electronic structure of
      antiferromagnetic USb2 using ultrafast optical spectroscopy.
AB  - Ultrafast optical spectroscopy is used to study the antiferromagnetic f-electron
      system USb(2). We observe the opening of two charge gaps at low temperatures
      (</~45 K), arising from renormalization of the electronic structure. Analysis of
      our data indicates that one gap is due to hybridization between localized f
      electron and conduction electron bands, while band renormalization involving
      magnons leads to the emergence of the second gap. These experiments thus enable
      us to shed light on the complex electronic structure emerging at the Fermi
      surface in f-electron systems.

PMID- 23952444
TI  - Bulk nuclear polarization enhanced at room temperature by optical pumping.
AB  - Bulk (13)C polarization can be strongly enhanced in diamond at room temperature
      based on the optical pumping of nitrogen-vacancy color centers. This effect was
      confirmed by irradiating single crystals at a ~50 mT field promoting
      anticrossings between electronic excited-state levels, followed by shuttling of
      the sample into an NMR setup and by subsequent (13)C detection. A nuclear
      polarization of ~0.5%--equivalent to the (13)C polarization achievable by thermal
      polarization at room temperature at fields of ~2000 T--was measured, and its bulk
      nature determined based on line shape and relaxation measurements. Positive and
      negative enhanced polarizations were obtained, with a generally complex but
      predictable dependence on the magnetic field during optical pumping. Owing to its
      simplicity, this (13)C room temperature polarizing strategy provides a promising
      new addition to existing nuclear hyperpolarization techniques.

PMID- 23952445
TI  - Midair collisions enhance saltation.
AB  - Here we address the old question in aeolian particle transport about the role of
      midair collisions. We find that, surprisingly, these collisions do enhance the
      overall flux substantially. The effect depends strongly on restitution
      coefficient and wind speed. We can explain this observation as a consequence of a
      soft bed of grains which floats above the ground and reflects the highest flying
      particles. We make the unexpected observation that the flux is maximized at an
      intermediate restitution coefficient of about 0.7, which is comparable to values
      experimentally measured for collisions between sand grains. 

PMID- 23952447
TI  - Interplay between folding and assembly of fibril-forming polypeptides.
AB  - Polypeptides can self-assemble into hierarchically organized fibrils consisting
      of a stack of individually folded polypeptides driven together by hydrophobic
      interaction. Using a coarse-grained model, we systematically studied this self
      assembly as a function of temperature and hydrophobicity of the residues on the
      outside of the building block. We find the self-assembly can occur via two
      different pathways-a random aggregation-folding route and a templated-folding
      process-thus indicating a strong coupling between folding and assembly. The
      simulation results can explain experimental evidence that assembly through
      stacking of folded building blocks is rarely observed, at the experimental
      concentrations. The model thus provides a generic picture of hierarchical fibril
      formation. 

PMID- 23952446
TI  - Eddy viscosity in dense granular flows.
AB  - We present a seminal set of experiments on dense granular flows in the stadium
      shear geometry. The advantage of this geometry is that it produces steady shear
      flow over large deformations, in which the shear stress is constant. The striking
      result is that the velocity profiles exhibit an S shape, and are not linear as
      local constitutive laws would predict. We propose a model that suggests this is a
      result of wall perturbations which span through the system due to the nonlocal
      behavior of the material. The model is analogous to that of eddy viscosity in
      turbulent boundary layers, in which the distance to the wall is introduced to
      predict velocity profiles. Our findings appear pivotal in a number of
      experimental and practical situations involving dense granular flows next to a
      boundary. They could further be adapted to other similar materials such as dense
      suspensions, foams, or emulsions. 

PMID- 23952448
TI  - Extrinsic noise driven phenotype switching in a self-regulating gene.
AB  - Analysis of complex gene regulation networks gives rise to a landscape of
      metastable phenotypic states for cells. Heterogeneity within a population arises
      due to infrequent noise-driven transitions of individual cells between nearby
      metastable states. While most previous works have focused on the role of
      intrinsic fluctuations in driving such transitions, in this Letter we investigate
      the role of extrinsic fluctuations. First, we develop an analytical framework to
      study the combined effect of intrinsic and extrinsic noise on a toy model of a
      Boolean regulated genetic switch. We then extend these ideas to a more
      biologically relevant model with a Hill-like regulatory function. Employing our
      theory and Monte Carlo simulations, we show that extrinsic noise can
      significantly alter the lifetimes of the phenotypic states and may fundamentally
      change the escape mechanism. Finally, our theory can be readily generalized to
      more complex decision making networks in biology.

PMID- 23952449
TI  - Effects of sequence and solvation on the temperature-pressure conformational
      landscape of proteinlike heteropolymers.
AB  - We study the role of sequence and solvation in shaping the temperature-pressure
      (T, P) conformational landscape of model heteropolymers with a coarse-grained
      model. We design foldable primarily hydrophobic sequences with fixed polar
      content in water at physiological conditions, which demonstrate (T, P) dependence
      of conformational stability similar to biological proteins. Inherent helicity
      emerges as a result of local polar-polar interactions in the sequences that mimic
      biological alpha helices. The helical propensity is reduced upon solvation and
      remains unaltered at cold T and high P, which is driven by the T-P induced
      changes of the hydration shell. Consequently, at nonphysiological conditions the
      weakening of hydrophobic interactions facilitates population of non-native,
      helical, compact conformations stabilized through direct nonlocal interactions
      between polar residues. 

PMID- 23952451
TI  - Aggregated markov model using time series of single molecule dwell times with
      minimum excessive information.
AB  - Statistics of the dwell times, the stationary state distributions (SSDs), are
      often studied to infer the underlying kinetics from a single molecule finite
      level time series. However, it is well known that the underlying kinetic scheme,
      a hidden Markov model (HMM), cannot be identified uniquely from the SSDs because
      some features of the underlying HMM are hidden by finite-level measurements.
      Here, we quantify the amount of excessive information in a given HMM that is not
      warranted by the measured SSDs and extract the HMM with minimum excessive
      information as the most objective representation of the data. The method is
      applied to a single molecule enzymatic turnover experiment, and the origin of
      dynamic disorder is discussed in terms of the network properties of the HMM. 

PMID- 23952450
TI  - Transcriptional delay stabilizes bistable gene networks.
AB  - Transcriptional delay can significantly impact the dynamics of gene networks.
      Here we examine how such delay affects bistable systems. We investigate several
      stochastic models of bistable gene networks and find that increasing delay
      dramatically increases the mean residence times near stable states. To explain
      this, we introduce a non-Markovian, analytically tractable reduced model. The
      model shows that stabilization is the consequence of an increased number of
      failed transitions between stable states. Each of the bistable systems that we
      simulate behaves in this manner. 

PMID- 23952452
TI  - Capillary force on a micrometric sphere trapped at a fluid interface exhibiting
      arbitrary curvature gradients.
AB  - We report theoretical predictions and measurements of the capillary force acting
      on a spherical colloid smaller than the capillary length that is placed on a
      curved fluid interface of arbitrary shape. By coupling direct imaging and
      interferometry, we are able to measure the in situ colloid contact angle and to
      correlate its position with respect to the interface curvature. Extremely tiny
      capillary forces down to femtonewtons can be measured with this method.
      Measurements agree well with a theory relating the capillary force to the
      gradient of Gaussian curvature and to the mean curvature of the interface prior
      to colloidal deposition. Numerical calculations corroborate these results.

PMID- 23952453
TI  - Growing multiplex networks.
AB  - We propose a modeling framework for growing multiplexes where a node can belong
      to different networks. We define new measures for multiplexes and we identify a
      number of relevant ingredients for modeling their evolution such as the coupling
      between the different layers and the distribution of node arrival times. The
      topology of the multiplex changes significantly in the different cases under
      consideration, with effects of the arrival time of nodes on the degree
      distribution, average shortest path length, and interdependence. 

PMID- 23952454
TI  - Coevolution and correlated multiplexity in multiplex networks.
AB  - Distinct channels of interaction in a complex networked system define network
      layers, which coexist and cooperate for the system's function. Towards
      understanding such multiplex systems, we propose a modeling framework based on
      coevolution of network layers, with a class of minimalistic growing network
      models as working examples. We examine how the entangled growth of coevolving
      layers can shape the network structure and show analytically and numerically that
      the coevolution can induce strong degree correlations across layers, as well as
      modulate degree distributions. We further show that such a coevolution-induced
      correlated multiplexity can alter the system's response to the dynamical process,
      exemplified by the suppressed susceptibility to a social cascade process. 

PMID- 23952455
TI  - Comment on "Scattering forces from the curl of the spin angular momentum of a
      light field".

PMID- 23952456
TI  - Marques and Saenz reply.

PMID- 23952457
TI  - New selenites: hydrothermal syntheses, crystal structures, and characterization
      of Rb3HGa2(OH)2(SeO3)4, Rb3Ga5(SeO3)8(HSeO3)2.0.5H2O, and RbGa(SeO3)2.H2O.
AB  - Three new gallium selenites, Rb3HGa2(OH)2(SeO3)4, Rb3Ga5(SeO3)8(HSeO3)2.0.5H2O,
      and RbGa(SeO3)2.H2O, have been synthesized by hydrothermal reactions using
      Rb2CO3, Ga(NO3)3.xH2O, and SeO2 as reagents. Rb3HGa2(OH)2(SeO3)4 consists of
      unidimensional corner-linked chains of GaO4(OH)2 that are connected by a SeO3
      group, whereas Rb3Ga5(SeO3)8(HSeO3)2.0.5H2O and RbGa(SeO3)2.H2O exhibit three
      dimensional frameworks consisting of three, mutually perpendicular, eight
      membered rings (8-MRs). In all three reported materials, Se(4+) is in an
      asymmetric coordination environment attributable to the stereoactive lone pair.
      Ion-exchange reactions, infrared spectroscopy, thermal analysis, elemental
      analysis, and dipole moment calculations for the reported materials are also
      presented. Crystal data: Rb3HGa2(OH)2(SeO3)4, orthorhombic, space group Cmca (No.
      64), with a = 7.17890(10) A, b = 18.0925(2) A, c = 12.6972(2) A, and Z = 4;
      Rb3Ga5(SeO3)8(HSeO3)2.0.5H2O, triclinic, space group P-1 (No. 2), with a =
      10.7727(2) A, b = 12.5372(3) A, c = 12.6952(3) A, alpha = 87.210(10) degrees ,
      beta = 85.447(10) degrees , gamma = 72.519(10) degrees , and Z = 2;
      RbGaSe2O6.H2O, triclinic, space group P-1 (No. 2), with a = 8.7027(6) A, b =
      9.7622(7) A, c = 15.3347(14) A, alpha = 105.622(4) degrees , beta = 90.210(4)
      degrees , gamma = 116.385(2) degrees , and Z = 2. 

PMID- 23952458
TI  - Analysis of different material theories used in a FE model of a lumbar segment
      motion.
AB  - In this study, a nonlinear poroelastic model of intervertebral disc as an
      infrastructure was developed. Moreover, a new element was defined consisting a
      disc (Viscoelastic Euler Beam Element) and a vertebra (Rigid Link) as a unit
      element. Using the new element, three different viscoelastic finite element
      models were prepared for lumbar motion segment (L4/L5). Prolonged loading (short
      term and longterm creep) and cyclic loading were applied to the models and the
      results were compared with results of in vivo tests. Simplification of the models
      by using the new element leads to reduction of the runtime of the models in
      dynamic analyses to few minutes without losing the accuracy in the results. 

PMID- 23952459
TI  - How we rate: is impact factor the most important measure?

PMID- 23952460
TI  - Switch and gain - sequential moxifloxacin monotherapy.

PMID- 23952461
TI  - Lower, faster, better: the delusions of surrogate markers in hypertension.

PMID- 23952462
TI  - Chiropractic and stroke: association or causation?

PMID- 23952463
TI  - Sequential intravenous/oral moxifloxacin monotherapy for complicated skin and
      skin structure infections: a meta-analysis of randomised controlled trials.
AB  - OBJECTIVES: The presumed superiority of moxifloxacin for the treatment of
      complicated skin and skin structure infections (cSSSIs) is based on laboratory
      data, but has not yet been established on clinical grounds. The aim of this meta
      analysis was to evaluate the efficacy and safety of sequential intravenous
      (i.v.)/oral (p.o.) moxifloxacin monotherapy for the treatment of cSSSIs. METHODS:
      Randomised controlled trials (RCTs) published prior to November 2012 were
      systematically retrieved from PubMed, MEDLINE, EMBASE, ScienceDirect,
      ClinicalTrials.gov and the Cochrane Central Register of Controlled Trials.
      Finally, a meta-analysis of all RCTs eligible for inclusion criteria was
      performed. RESULTS: Three studies that enrolled 2255 patients were included in
      the meta-analysis. There were no statistically significant differences between
      patients given moxifloxacin and those given other antibiotics with regard to
      clinical success rate [1667 patients, odds ratio (OR) = 0.83, 95% confidence
      interval (CI) 0.63 to 1.09, p = 0.18], bacteriological success rate
      (bacteriological success rates: 1502 patients, OR = 0.90, 95% CI 0.68-1.18, p =
      0.45) or mortality (2207 patients, OR = 1.96, 95% CI 0.79-4.88, p = 0.15).
      Significantly, more overall adverse events (AEs) were associated with the use of
      moxifloxacin than with other antibiotics (2207 patients, OR = 1.21, 95%CI 1.00
      1.45, p = 0.04). However, there was no statistically significant difference in
      the occurrence of drug-related AEs, serious AEs or serious drug-related AEs
      between patients given moxifloxacin and those given other antibiotics.
      CONCLUSION: Sequential i.v./p.o. moxifloxacin monotherapy is an effective and
      relatively safe option for the treatment of cSSSIs. Other benefits of
      moxifloxacin may make it a more viable option compared with the currently used
      regimens.

PMID- 23952464
TI  - Early combination therapy with telmisartan plus amlodipine for rapid achievement
      of blood pressure goals.
AB  - BACKGROUND: Rapid and sustained blood pressure (BP) goal attainment is important
      to reduce cardiovascular risk. Initial use of combination therapy may improve BP
      goal attainment. METHODS: The Boehringer Ingelheim trial database was searched
      for randomised, double-blind studies comparing telmisartan/amlodipine combination
      therapy with monotherapy. Eight studies were identified. Eight separate analyses
      were used to compare combination therapy with respective monotherapies at the
      earliest available time points (weeks 1, 2 and/or 4). RESULTS: In patients
      initiated on combination therapy, greater systolic BP (SBP)/diastolic BP (DBP)
      reductions were seen with combination therapy (p < 0.0001); BP (< 140/90 mmHg),
      SBP (< 140 mmHg) and DBP (< 90 mmHg) goal attainment rates were significantly
      higher with combination therapy at all time points. In patients uncontrolled by
      monotherapy, greater SBP/DBP reductions were seen with combination therapy (p <
      0.05 in all but one measure), and all goal attainment rates were significantly
      higher with combination therapy, except in one measure. CONCLUSION: Many people
      can achieve their BP targets when taking a combination of telmisartan and
      amlodipine after failing to do so with monotherapy. Furthermore, BP targets can
      be achieved more rapidly using a combination of telmisartan and amlodipine as
      initial therapy than with either monotherapy.

PMID- 23952465
TI  - The urodynamic characteristics and prognostic factors of patients with
      interstitial cystitis/bladder pain syndrome.
AB  - AIMS: The role of urodynamic study (UDS) in diagnosis of interstitial
      cystitis/bladder pain syndrome (IC/BPS) remains inconclusive, nor has the
      predictor for a treatment success been elucidated. We evaluated the diagnostic
      and prognostic values of UDS in patients with IC/BPS. MATERIALS AND METHODS:
      IC/BPS patients with complete data of a symptom assessment, video UDS, potassium
      chloride (KCl) test, cystoscopic hydrodistention and treatment records were
      reviewed retrospectively. O'Leary-Sant symptom index and problem index (ICSI,
      ICPI) were available in part of the patients. The associations between UDS
      parameters with symptom scores, KCl test result, cystoscopy findings and
      treatment outcome were analysed. The UDS parameters, including first sensation of
      filling (FSF), first desire to void (FD), strong desire to void (SD), cystometric
      bladder capacity (CBC), maximum flow rate (Q(max)), detrusor pressure at Q(max)
      (Pdet), voided volume (VV) and postvoid residual (PVR). Univariate and
      multivariate logistic regression analyses were used to identify the variable
      predicting treatment success. RESULTS: A total of 214 IC/BPS patients were
      enrolled in this study. The mean volumes at FSF, FD, SD, CBC and VV were
      inversely correlated with ICSI and ICPI (all p < 0.05). The patients with a
      positive KCl test had significantly lower mean volumes at SD, CBC, VV and lower
      Q(max) (all p < 0.05). Significantly lower mean volumes for FSF, FD, SD, CBC and
      VV were found in patients with higher grade of glomerulation under cystoscopy
      (all p < 0.01). The anaesthetic maximal bladder capacity (MBC) was positively
      correlated with FSF, FD, SD, CBC, Q(max) and VV (all p < 0.01). Female gender and
      the volume at SD were found to be the independent predictors for treatment
      outcome. CONCLUSIONS: Our study demonstrated that there might be a role of UDS to
      help in diagnosis and prognostication for IC/BPS. Future prospective
      investigations are warranted.

PMID- 23952466
TI  - Evaluation of patient outcome after discontinuation of alfuzosin treatment for
      benign prostatic hyperplasia: a multicentre, prospective study.
AB  - AIMS: The aim of this study was to assess patient outcome after discontinuation
      of alfuzosin treatment in patients with benign prostatic hyperplasia (BPH).
      METHODS: This study included 200 BPH patients. Alpha-blockers were discontinued
      after 12 weeks of treatment when the International Prostatic Symptom Score (IPSS)
      was reduced to < 8 points, peak urine flow rate (Q(max)) was increased to >= 15
      ml/s, the postvoiding residual (PVR) urine volume was <= 100 ml and the patient
      agreed to discontinue treatment. Urinary symptoms of the patients were assessed
      at 4, 8, 12 and 24 weeks after discontinuation of medication, and surveys were
      performed asking whether patients wanted to restart administration of medication.
      RESULTS: Of 200 enrolled patients, 142 (71.00%) received 12 weeks of treatment
      with 10 mg of alfuzosin. The medication was discontinued in 58 of 142 patients
      (40.85%) because urinary symptoms had improved. Among these patients, follow-up
      observations were performed for 49 patients up to 24 weeks after treatment
      discontinued. Of these 49 patients, 28 (57.14%) showed correct urination without
      a need to restart treatment up to 24 weeks after the medication was discontinued.
      The discontinuation group demonstrated improved voiding symptoms, including
      Q(max) and PVR, relative to the re-administration group at baseline. Furthermore,
      the discontinuation group showed a smaller prostate volume than the re
      administration group (p = 0.045). CONCLUSION: When patients with BPH displayed
      symptomatic improvement upon treatment with alpha-blockers, the improvements were
      maintained in a select subpopulation of patients without the need to re
      administer the alpha-blockers.

PMID- 23952468
TI  - Complex cases in primary care: report of a CME-certified series addressing
      patients with multiple comorbidities.
AB  - AIM: To assess whether participation in a series of continuing medical education
      certified activities presenting complicated case scenarios resulted in evidence
      based decision making for patients with chronic comorbid conditions. METHODS: A
      series of interactive live workshops and online case studies presented evidence
      based, practical information addressing the care of patients with multiple
      chronic diseases to primary care physicians. Clinical case vignettes were used to
      assess workshop participant knowledge and competence. Results were compared with
      those of matched non-participant controls. Online participants were surveyed to
      evaluate immediate knowledge gains from the activity. RESULTS: Overall, physician
      workshop participants were 27% more knowledgeable of evidence-based treatment
      decisions. Participants were more likely to refer a patient with rheumatoid
      arthritis to a rheumatologist (57% vs. 36%; p = 0.035) and showed better
      recognition of medications that can contribute to overactive bladder symptoms
      (36% vs. 18%; p = 0.043) compared with non-participant controls. Non-significant
      differences in favour of participants included evidence-based decisions regarding
      the management of osteoporosis, attention deficit hyperactivity disorder in
      adults and type 2 diabetes mellitus in adolescents. Online participants
      demonstrated significant knowledge gains (p < 0.001) on 17 of 18 assessment
      questions across all therapeutic areas. DISCUSSION: Chronic comorbid conditions
      afflict a sizable minority of patients. However, specific recommendations and
      education surrounding patient management are often overlooked because of the
      inherent difficulty of treating this group. Highly interactive educational
      activities can improve participant knowledge and competency in treating these
      patients by providing an opportunity to interact with faculty experts, receive
      immediate feedback and practice new skills. CONCLUSION: Interactive educational
      activities that discuss complicated case scenarios can improve participant
      application of evidence-based medicine for patients with multiple chronic
      comorbidities.

PMID- 23952467
TI  - Choice of early treatment regimen and impact on beta-cell preservation in type 2
      diabetes.
AB  - The progressive deterioration of glycaemic control in individuals with type 2
      diabetes mellitus (T2DM) results from insulin resistance combined with the
      ongoing loss of beta-cell function. Although it had been suggested that most beta
      cell dysfunction occurs after the development of T2DM, studies have documented a
      substantial early loss of beta-cell function, particularly during the prediabetic
      state. In patients diagnosed with T2DM, beta-cell function continues to decline
      despite treatment with commonly prescribed antihyperglycaemic medications, and
      ultimately exogenous insulin administration is required to maintain optimal
      glycaemic control. Thus, interventions to address the early decline in beta-cell
      function could potentially alter the course of T2DM, preventing or delaying its
      onset and decreasing the incidence of complications. Original research and review
      articles on this topic were identified in a PubMed search from January 2000
      through August 2012. Data from prospective studies and clinical trials suggest
      that lifestyle modifications and certain antihyperglycaemic medications,
      including thiazolidinediones (TZDs), glucagon-like peptide-1 (GLP-1) agonists,
      dipeptidyl peptidase-4 (DPP-4) inhibitors and insulin, may preserve or enhance
      beta-cell function. The implication of current data is that early initiation of
      lifestyle modifications and antihyperglycaemic agents that preserve beta-cell
      function might reverse or delay progression to T2DM in those with prediabetes.
      Moreover, improved beta-cell function may confer more durable glucose control and
      perhaps reduce/delay the incidence of diabetic complications. Long-term studies
      are needed to validate this hypothesis. 

PMID- 23952470
TI  - Bias and adverse effects of homeopathy: is scientific criticism in homeopathy a
      "mission impossible"?

PMID- 23952469
TI  - Safety and efficacy of tenofovir/emtricitabine or abacavir/lamivudine in
      combination with efavirenz in treatment naive HIV patients: a 5 year
      retrospective observational cohort study. (the TOKEN Study).

PMID- 23952471
TI  - Characterization of Mycobacterium salmoniphilum as causal agent of
      mycobacteriosis in Atlantic salmon, Salmo salar L., from a freshwater
      recirculation system.
AB  - Thirty Atlantic salmon, Salmo salar L., with low corporal condition relative to
      other fish present in the culture system, were sampled from a freshwater
      recirculation pisciculture located in Chile. The most characteristic signs and
      lesions were cachexia and presence of multiple greyish-white granulomas within
      internal organs. The external and internal lesions, along with the microscopic,
      histologic and biochemical findings, were consistent with mycobacteriosis. The
      identification of Mycobacterium salmoniphilum as the causal agent of the lesions
      was possible through the use of molecular analyses. This study represents the
      first report of Mycobacterium salmoniphilum in a freshwater recirculation system
      and the first case of fish mycobacteriosis described in Chile. 

PMID- 23952472
TI  - Temperature-driven flower longevity in a high-alpine species of Oxalis influences
      reproductive assurance.
AB  - How high-alpine plants confront stochastic conditions for animal pollination is a
      critical question. We investigated the effect of temperature on potential flower
      longevity (FL) measured in pollinator-excluded flowers and actual FL measured in
      pollinated flowers in self-incompatible Oxalis compacta and evaluated if
      plastically prolonged potential FL can ameliorate slow pollination under cool
      conditions. Pollinator-excluded and hand-pollinated flowers were experimentally
      warmed with open-top chambers (OTCs) on a site at 3470 m above sea level (asl).
      Flower-specific temperatures, and pollinator-excluded and open-pollination flower
      life-spans were measured at six alpine sites between 3100 and 3470 m asl. Fruit
      set was analyzed in relation to inferred pollination time. Warming reduced
      potential FL. Variable thermal conditions across the alpine landscape predicted
      potential and actual FL; flower senescence was pollination-regulated. Actual FL
      and potential FL were coupled. Prolonged potential FL generally increased fruit
      set under cooler conditions. Plastic responses permit virgin flowers of O.
      compacta to remain open longer under cooler temperatures, thereby ameliorating
      slow pollination, and to close earlier when pollination tends to be faster under
      warmer conditions. Plastic potential FL provides adaptive advantages in the cold,
      thermally variable alpine habitat, and has important implications for
      reproductive success in alpine plants in a warming world. 

PMID- 23952473
TI  - Pulsed-Field Gel Electrophoresis Proficiency Testing Trials: Toward European
      Harmonization of the Typing of Food and Clinical Strains of Listeria
      monocytogenes.
AB  - Abstract The European Union Reference Laboratory for Listeria monocytogenes (EURL
      for Lm) coordinates a European network of 35 National Reference Laboratories
      (NRLs), most of which perform food, environmental, and veterinary Lm strain
      surveillance in their respective countries. The EURL activities resulted in the
      recent creation of a database (EURL Lm DB). Typing and related epidemiological
      data submitted to the EURL Lm DB will be collected and shared by all the NRLs.
      For a given NRL, the only criterion required in order to submit pulsed-field gel
      electrophoresis (PFGE) profiles to the database was the successful participation
      with at least one EURL PFGE and PFGE profile interpretation Proficiency Testing
      (PT) trial. In this context, the EURL organized a PT trial in 2012 to evaluate
      the NRL's ability to perform PFGE and profile interpretation. A total of 18 NRLs
      took part in this study. Upon request from the Food- and Waterborne Diseases and
      Zoonoses Programme of the European Centre for Disease Prevention and Control, 10
      National Public Health Reference Laboratories (NPHLs) also took part in this PT
      trial. Of the 28 participating laboratories, 16 obtained results classified as
      "good" or "satisfactory." These 16 laboratories included 10 NRLs (56%) and 6
      NPHLs (60%). Of the 22 NRLs and NHPLs that participated in the part of the PT
      trial related to PFGE profile interpretation, 11 laboratories obtained good
      results. These 11 laboratories included eight NRLs, which therefore can now
      submit profiles to the EURL Lm DB. This PT trial provided a valuable opportunity
      to facilitate and to stimulate the sharing of reproducible PFGE profiles between
      human and food reference laboratories.

PMID- 23952474
TI  - Influence of acid-adaptation of Campylobacter jejuni on adhesion and invasion of
      INT 407 cells.
AB  - The aim of this study was to determine the influence of acid-adaptation on the
      survival as well as adhesion and invasion of human intestinal cells by nine
      Campylobacter jejuni strains after exposure to different stress conditions. Acid
      adapted and nonadapted C. jejuni were exposed to different secondary stress
      conditions such as acid (pH 4.5), starvation (phosphate-buffered saline, pH 7.2),
      or salt (3% wt/vol NaCl). After exposure to the secondary stress, the adhesion
      and invasion abilities of the strains were evaluated in vitro in tissue culture
      using the human intestinal cell line INT 407. The survival rates of acid-adapted
      cells of some strains of C. jejuni exposed to different secondary stresses were
      found to be significantly higher than the non-acid-adapted cells. Similarly, some
      strains also showed an increase in adhesion and invasion (p<0.05) when acid
      adapted C. jejuni were exposed to stresses such as acid, starvation, or salt as
      compared to non-acid-adapted C. jejuni. We found that adaptation to acid stress
      can enhance the survival of C. jejuni when exposed to secondary stresses and,
      thus, result in increased adhesion and invasion of human intestinal cells in
      vitro. However, the survival rates as well as the degree of adhesion and invasion
      were found to vary with the strain of C. jejuni, the time of adaptation to acid,
      the type of the secondary stress and exposure time to the secondary stress. These
      results show that adaptation to stresses could influence virulence of C. jejuni.
      Understanding the conditions by which C. jejuni adapts to stresses will provide
      information concerning how this organism is able to survive inside and outside
      the host. This, in turn, could offer methods to reduce or eliminate C. jejuni in
      the environment.

PMID- 23952475
TI  - Cold shock proteins contribute to the regulation of listeriolysin O production in
      Listeria monocytogenes.
AB  - Cold shock proteins (Csps) are multifunctional nucleic acid binding proteins used
      to regulate a wide range of gene expression responses in bacteria. We report here
      that Csps regulate the production of the pore-forming cytolysin listeriolysin
      (LLO) and hemolysis phenotypes in Listeria monocytogenes. A triple csp gene
      deletion mutant incapable of producing any Csps, as well as double csp gene
      deletion mutants only producing either CspA or CspD, caused less hemolysis and
      produced lower LLO concentration. On the other hand, another double csp gene
      deletion mutant that produces CspB retained hemolysis and LLO production levels
      that are similar to the parental wild-type strain. Transcription analysis showed
      that in absence of all three csp genes or cspB alone, L. monocytogenes cells have
      decreased levels of hly gene transcripts, which code for the synthesis of LLO
      proteins. A comparative examination of mRNA stability showed that hly transcripts
      were more rapidly degraded in L. monocytogenes triple csp gene deletion mutant
      cells that are not capable of producing Csps. Overall, our results indicate that
      Csps, in particular CspB, are important components of gene expression regulatory
      mechanisms that promote efficient LLO production and hence virulence responses of
      L. monocytogenes.

PMID- 23952476
TI  - Electronic health records: new opportunities for clinical research.
AB  - Clinical research is on the threshold of a new era in which electronic health
      records (EHRs) are gaining an important novel supporting role. Whilst EHRs used
      for routine clinical care have some limitations at present, as discussed in this
      review, new improved systems and emerging research infrastructures are being
      developed to ensure that EHRs can be used for secondary purposes such as clinical
      research, including the design and execution of clinical trials for new
      medicines. EHR systems should be able to exchange information through the use of
      recently published international standards for their interoperability and
      clinically validated information structures (such as archetypes and international
      health terminologies), to ensure consistent and more complete recording and
      sharing of data for various patient groups. Such systems will counteract the
      obstacles of differing clinical languages and styles of documentation as well as
      the recognized incompleteness of routine records. Here, we discuss some of the
      legal and ethical concerns of clinical research data reuse and technical security
      measures that can enable such research while protecting privacy. In the emerging
      research landscape, cooperation infrastructures are being built where research
      projects can utilize the availability of patient data from federated EHR systems
      from many different sites, as well as in international multilingual settings.
      Amongst several initiatives described, the EHR4CR project offers a promising
      method for clinical research. One of the first achievements of this project was
      the development of a protocol feasibility prototype which is used for finding
      patients eligible for clinical trials from multiple sources. 

PMID- 23952477
TI  - Molecular analysis for patients with IL-12 receptor beta1 deficiency.
AB  - Autosomal recessive interleukin-12 receptor beta1 (IL-12Rbeta1) deficiency has
      been described as the most common cause of Mendelian susceptibility to
      mycobacterial disease (MSMD), characterized by clinical disease due to weakly
      virulent mycobacteria such as Bacille Calmette-Guerin (BCG) vaccines and
      environmental mycobacteria (EM) in children who are normally resistant to most
      infectious agents. Here, we report the cases of five patients with mycobacterial
      infection, including one with systemic lupus erythematosus (SLE). Blood samples
      from patients and healthy controls were activated in vitro with BCG, BCG+IL-12,
      and BCG+IFN-gamma. The results showed reduced or no production of IFN-gamma after
      IL-12 stimulation in all samples. IL-12Rbeta1 expression on the cell surface was
      negligible or absent. Genetic analysis showed five novel mutations. 

PMID- 23952478
TI  - Protective mechanism of morin against ultraviolet B-induced cellular senescence
      in human keratinocyte stem cells.
AB  - PURPOSE: Ultraviolet-B (UVB) irradiation is a major inducer of DNA damage in the
      epidermis. Here we investigated the protective mechanism of polyphenolic
      phytonutrient, morin against UVB-induced DNA damage in human keratinocyte stem
      cells (KSC). RESULTS AND CONCLUSIONS: After confirming the characteristics of the
      KSC, we examined the protective ability of morin against the cell damage of KSC
      under UVB irradiation condition. As a result, morin significantly inhibited the
      UVB-induced damage to KSC. These inhibitory effects by morin were also confirmed
      by the senescence-associated beta-galactosidase and alkaline comet assays. Next,
      we monitored the effects of morin on the UVB-induced production of inflammatory
      cytokines. Morin significantly decreased the production of tumor necrosis factor
      alpha, interleukin-1beta, and interleukin-6 in the UVB-irradiated KSC. Also,
      morin significantly inhibited the UVB-induced phosphorylation of ataxia
      telangiectasia mutated (ATM), serine threonine kinase checkpoint kinase 2, tumor
      suppressor protein 53 (p53), c-Jun N-terminal kinase/stress-activated protein
      kinase, p38/mitogen-activated protein kinase, S6 ribosomal protein, and histone
      2A family member X in KSC. Furthermore, while UVB irradiation induced p53
      reporter activation in KSC, morin significantly inhibited UVB-induced p53
      reporter activation in KSC. In addition, mouse double minute 2 homolog (MDM2, p53
      E3 ubiquitin protein ligase) inhibitor significantly increased the p53 reporter
      activation in the UVB-irradiated KSC, but morin decreased the MDM2 inhibitor
      mediated increase in p53 reporter activation. On the contrary, ATM inhibitor did
      not affect the protective effect of morin in UVB irradiation-induced p53 reporter
      activation. Collectively, these findings suggest that morin could effectively
      enrich the p53 specific ligasing ability of MDM2 in UVB irradiation-induced p53
      activation.

PMID- 23952480
TI  - Serum biomarkers in elderly asthma.
AB  - OBJECTIVE: Asthma is usually misdiagnosed and under-treated in the elderly
      population, resulting in complications and increased severity to the patient. In
      this review, we describe some of the most important serum markers of asthma
      studied so far, reporting their outcomes and possible prediction of asthma in the
      elderly population. METHODS: The PubMed electronic database was used to search
      for promising serum biomarkers of asthma studied in original articles published
      in peer-reviewed journals from 2000 to January 2013. RESULTS: A total of 13
      relevant serum biomarkers were selected, including IgE, CRP, high sensitive CRP,
      IL-6, IL-8, IL-17, TNF-alpha, neopterin, serum amyloid A, eosinophil cationic
      protein, leukolysin, YKL-40 and soluble CD86. CONCLUSIONS: Although the major
      focus of treatment and research has been on allergic asthma, several forms of the
      disease are recognized, such as neutrophilic asthma, which is characteristic of
      older patients. Different phenotypes imply different treatments and so it becomes
      important to correctly determine which type of asthma the patient is suffering
      from. Serum markers capable of supporting a diagnosis of asthma are needed in
      order to counter mistreatment and misdiagnosis with other obstructive airways
      disease (OAD) in elderly patients. As convenient as serum markers may seem to be,
      a marker capable of accurately identifying asthma with sufficient specificity is
      yet to be found.

PMID- 23952481
TI  - Low hepatitis B vaccine response in children with Down syndrome from Brazil.
AB  - BACKGROUND: It has been reported that vaccination against hepatitis B is less
      effective among people with Down syndrome than in the general population. We
      aimed to evaluate the rate of seroconversion to hepatitis B vaccine in children
      with Down syndrome from Brazil. METHODS: A total of 120 people with Down syndrome
      were included. All of them received the vaccine at intervals of 0, 30 and 180
      days and serum samples were tested for the presence of antibodies to the
      hepatitis B surface antigen (anti-HBs) 30 days after the last dose. RESULTS: In
      the studied group, 58.3% (70/120) were male and 41.7% (50/120) female, with the
      median age of 5 years (range 2-15 years). Fifty-eight of 120 (48.3%) developed
      anti-HBs after vaccination. No association was found between gender and/or age
      and vaccine response. CONCLUSIONS: The low rate of seroconversion in response to
      hepatitis B vaccine suggests that all patients with Down syndrome immunized
      against hepatitis B should be followed and monitored by clinicians.

PMID- 23952479
TI  - Allostery and substrate channeling in the tryptophan synthase bienzyme complex:
      evidence for two subunit conformations and four quaternary states.
AB  - The allosteric regulation of substrate channeling in tryptophan synthase involves
      ligand-mediated allosteric signaling that switches the alpha- and beta-subunits
      between open (low activity) and closed (high activity) conformations. This
      switching prevents the escape of the common intermediate, indole, and
      synchronizes the alpha- and beta-catalytic cycles. (19)F NMR studies of bound
      alpha-site substrate analogues, N-(4'-trifluoromethoxybenzoyl)-2-aminoethyl
      phosphate (F6) and N-(4'-trifluoromethoxybenzenesulfonyl)-2-aminoethyl phosphate
      (F9), were found to be sensitive NMR probes of beta-subunit conformation. Both
      the internal and external aldimine F6 complexes gave a single bound peak at the
      same chemical shift, while alpha-aminoacrylate and quinonoid F6 complexes all
      gave a different bound peak shifted by +1.07 ppm. The F9 complexes exhibited
      similar behavior, but with a corresponding shift of -0.12 ppm. X-ray crystal
      structures show the F6 and F9 CF3 groups located at the alpha-beta subunit
      interface and report changes in both the ligand conformation and the surrounding
      protein microenvironment. Ab initio computational modeling suggests that the
      change in (19)F chemical shift results primarily from changes in the alpha-site
      ligand conformation. Structures of alpha-aminoacrylate F6 and F9 complexes and
      quinonoid F6 and F9 complexes show the alpha- and beta-subunits have closed
      conformations wherein access of ligands into the alpha- and beta-sites from
      solution is blocked. Internal and external aldimine structures show the alpha-
      and beta-subunits with closed and open global conformations, respectively. These
      results establish that beta-subunits exist in two global conformational states,
      designated open, where the beta-sites are freely accessible to substrates, and
      closed, where the beta-site portal into solution is blocked. Switching between
      these conformations is critically important for the alphabeta-catalytic cycle. 

PMID- 23952482
TI  - Chronic implantation of intravascular cardioverter defibrillator in a canine
      model: device stability, vascular patency, and anchor histology.
AB  - INTRODUCTION: A percutaneously placed implantable intravascular defibrillator
      (PICD) has been developed with a right ventricular (RV) single-coil lead and
      titanium electrodes in the superior vena cava (SVC) and the inferior vena cava
      (IVC). This study evaluated implant techniques, device stability, and anchor
      histology of the PICD over 9 months in a canine model. METHODS: Twenty-four
      hounds (wt = 30-55 kg) were anesthetized and a custom sheath introduced into the
      right femoral vein. The PICD was advanced over a wire and positioned with the
      titanium electrodes (cathodes) in the SVC and the IVC. A nitinol anchor secured
      the device in the jugular. The RV lead was positioned in the RV apex and screwed
      into place. The catheters, wires, and sheath were removed with an average implant
      time of 14 minutes. In one group of animals (n = 13), serial venograms were
      performed at 7 days, 14 days, and 28 days. In a second group (n = 6) and third
      group (n = 5), venograms were also performed at 90 days and 270 days,
      respectively. Six canines were sacrificed and anchor histologic examination done
      at 90 days. RESULTS: All implants were successful with no surgical complications
      observed. Devices (N = 24) remained appropriately positioned with no anchor
      migration. Histology at 90 days showed 98% endothelialization of the anchor.
      Venograms revealed patent IVC and jugular veins in all animals at every time
      point examined. CONCLUSIONS: The PICD can be rapidly and chronically implanted in
      animals. Long-term intravascular defibrillator placement is feasible in a canine
      model.

PMID- 23952484
TI  - Preface.
AB  - No abstract available for this article. 

PMID- 23952485
TI  - Introduction.
AB  - No abstract available for this article. 

PMID- 23952483
TI  - Intellectual disability and co-occurring mental health and physical disorders in
      aggressive behaviour.
AB  - BACKGROUND: Mental and physical health problems are more prevalent among
      individuals with an intellectual disability (ID) than in the general population.
      Studies suggest that there may be significant associations between these co
      occurring disorders and aggressive behaviour, but few studies have taken into
      account multiple mental and physical problems, as well as their level of
      severity. OBJECTIVES: The main goal of this study was to identify the
      associations between different types of aggressive behaviour and various types of
      physical and mental health problems. METHODS: These associations were explored
      through a cross-sectional study of 296 adult men and women with mild or moderate
      ID living in the community and receiving ID services. Information was gathered
      through interviews with ID participants, case managers and file review. RESULTS:
      The results show that individuals with ID who have more mental and physical
      health problems have higher odds of displaying aggressive behaviour than those
      with fewer and less severe physical health problems. DISCUSSION: These results
      can help guide future prevention and intervention strategies for persons with ID
      who display aggressive behaviour or who are at risk of become aggressive.

PMID- 23952486
TI  - Development of the ADL Profile.
AB  - This article presents a new instrument, the ADL Pcofile, which is designed
      specifically for the head injured adult. The instrument is based on the model of
      occupational performance and on Luria's model of cerebral and motor functioning.
      It divides the concept of activities of daily living (ADL) into 3 dimensions:
      personal environment, home environment and community environment. It further
      delineates a number of activities, tasks and operations under each of these
      dimensions. The article presents a rationale for the instrument's development, a
      description of the development process and the preliminary validation work, and
      details of the instrument itself. 

PMID- 23952487
TI  - Measuring clinical change in cognitive rehabilitation of patients with brain
      damage.
AB  - The purpose of this article is to demonstrate the use of the Loewenstein
      Occupational Therapy Cognitive Assessment (LOTCA) as a measure of clinical change
      in the cognitive rehabilitation of brain damaged patients. Two cases are
      presented, one a traumatic brain injured (TBI) young male patient and the second
      an elderly male patient suffering from cerebral vascular accident (CVA).
      Evaluation and treatment combined sensoly motor stimulation, cognitive
      remediation and functional approaches. Profiles of cognitive performance to
      follow-up progress during the process of recovery are presented. Recommendations
      are made to utilize occupational therapy ongoing assessments for documenting
      clinical change. 

PMID- 23952488
TI  - Goal attainment scaling in post-acute outpatient brain injury rehabilitation.
AB  - Therapists continuously strive for efficiency in clinical practice. Goal
      Attainment Scaling (GAS) is a tool that can provide both a structure for
      objective documentation of patient progress and a means of program evaluation.
      This article describes the application of GAS in a comprehensive outpatient brain
      injury rehabilitation program. The benefits of GAS include: (1) objective data in
      monitoring participants' progress, (2) a structure for team confer-. ences, (3)
      facilitation of on oing rehabilitation planning and decision- making, (4) concise
      relevant information to funding sources, referral sources, and family members,
      and (5) a mechanism for program evaluation. For the brain injured person, GAS
      serves as a focus for an arra of multiple, often abstract rogram goals. GAS can
      also increase the participant's awareness of deficits being addressed in the
      program and of progress towards resolving these problems. 

PMID- 23952489
TI  - The TBIIM.
AB  - This article describes an intervention model for occupational therapists who
      treat individuals with traumatic brain injury. The model moves occupational
      therapy intervention beyond traditional skill acquisition in the clinical setting
      to the promotion of role function in the client's community environment. Concepts
      from the Model of Human Occupation, phenomenology and neurorehabilitation are
      integrated to provide the therapist with a set of guidelines for life-long
      intervention with individuals with traumatic brain injury. A case example is used
      to illustrate the model and implications for treatment and research are
      discussed. 

PMID- 23952490
TI  - Family intervention with the traumatically brain injured patient.
AB  - The occupational therapist plays an integral role in the evaluation and treatment
      of the traumatically brain injured (TBI) patient. Although the TBI patient's
      needs are relatively well-defined by the nature of the injury, less well
      recognized and frequently over- 1ooked is the emotional and psychological trauma
      experienced by the family of the TBI patient. Depending on the information
      provided, the family can be an asset or hindrance in the patient's
      rehabilitation. By working with the TBI patient's family, the occupational
      therapist can guide the family into a more cohesive force that will assist the
      patient throughout the rehabilitative process. This article provides suggestions
      to evaluate and manage concerns and fears raised by the families of TBI patients.
      It rovides an organizational guideline for educating the family about BI and
      incorporating them in the rehabilitation of the TBI patient. 

PMID- 23952491
TI  - A descriptive study of family directed therapy for traumatically brain injured
      persons.
AB  - Long term outcome after traumatic brain injury is a major concern for
      rehabilitation professionals, family members, and the general community because
      of the complex residual physical, social, cognitive and psychological problems
      associated with the disability. This paper reports the findings of an exploratory
      study investigating the nature of caregiving provided b family members in the
      community. Family directed therapy (FDt) is defined, and data about 22
      informants' patterns of FDT activities are described. The similarity of FDT to
      occupational therapy practice is discussed and implications for facilitating
      caregiver involvement in FDT described. 

PMID- 23952492
TI  - Executive function and cognitive remediation.
AB  - Through the use of multiple case study design, this project examined the
      variations in executive function exhibited by two subjects who sustained frontal
      lobe damage. The study then investigated the relationship between executive
      functional deficit and activity preference. Subjects were trained in computerized
      cognitive retraining and conventional cognitive retraining. Subjects were then
      asked to select either modality. Each subject was tested for initiation and
      overall executive function, cognitive status and disability level. Findings
      revealed that executive functional deficits present in varied and unique ways and
      that activity preferrence is related to the unique constellation of sequelae
      rather than location of injury. Further implications point to the value of
      combining informal and formal inquiry techniques to patient assessment as well as
      research on closed head injury intervention. 

PMID- 23952493
TI  - Stroke clients' perceptions of disability and treatment.
AB  - Twenty subjects who had experienced a stroke and were serving as a control group
      in a larger research project, were interviewed regarding the effect the stroke
      had had on their lives and their perceptions of the occupational therapy they had
      received. The majority of the subjects had very little understanding of the
      nature of a stroke but were well able to articulate the effect the stroke had had
      on their lives. How each person experienced a stroke was very different, yet the
      losses each felt related to North American values of independence, mobility,
      individual control and coping. Treatment received in occupational therapy was
      most commonly described in terms of games; very few people had grasped the notion
      that the central purpose of occupational therapy was to help them to perform
      daily living tasks independently. Therapists should consequently consider the use
      of more fu'nctionally oriented treatment. 

PMID- 23952494
TI  - Otdbase.
AB  - This article describes the rationale behind the development of an "only
      occupational therapy" computerized literature search service. OTDBASE, the
      clinically-oriented index and data base, contains all relevant information about
      all articles from eight occupational therapy (OT) journals from 1970 to the
      present and includes up to 10 lines of abstract per article. The service was
      developed for purposes of contributing to continuing education and research
      efforts in occupational therapy. 

PMID- 23952496
TI  - Effect of nitric oxide on antioxidative response and proline metabolism in banana
      during cold storage.
AB  - The effect of exogenous nitric oxide (NO) on chilling injury to banana fruit was
      investigated. Banana fruit was treated with NO donor sodium nitroprusside of 0.05
      mM at 20  degrees C for 10 min and then stored at 7  degrees C for up to 20 days.
      Banana fruit treated with NO sustained a lower chilling injury index and higher
      firmness and kept lower electrolyte leakage and malondialdehyde content than the
      control. Further investigation showed that NO treatment enhanced activities of
      guaiacol peroxidase, ascorbate peroxidase, and glutathione reductase compared to
      the control. It also maintained higher ascorbic acid, reduced glutathione
      content, and total antioxidant capacity but reduced hydrogen peroxide and
      superoxide anion to lower levels compared to control fruit during storage. NO
      treatment significantly enhanced the accumulation of total phenolics and proline,
      which resulted from the increased activities of phenylalanine ammonia-lyase and
      Delta1-pyrroline-5-carboxylate synthetase and decreased proline dehydrogenase
      activity. We proposed that the enhanced chilling tolerance induced by NO
      treatment may result from the reduction of oxidative stress and proline
      accumulation.

PMID- 23952497
TI  - Physicochemical characterization and toxicological evaluation of plant-based
      anionic polymers and their nanoparticulated system for ocular delivery.
AB  - The water-soluble fractions of mucilages and gum from the seeds of fenugreek,
      isphagula and mango bark exudate were isolated, purified and characterized using
      X-ray diffraction (XRD) spectrometry, Fourier transform infrared spectroscopy (FT
      IR), maldi/GC-MS, elemental analysis, 1D ((1)H and (13)C) and 2D (HMQC, COSY)
      nuclear magnetic resonance spectroscopy (NMR). The fenugreek mucilage was
      identified to be a galactomannan chain consisting of 4 units of galactose
      attached to the backbone of 6 mannose units in 1:1.5 ratio. The isphagula
      mucilage was identified to be an arabinoxylan polysaccharide chain consisting of
      4 units of arabinofuranose attached to the backbone of 9 xylopyrannose units in
      1:3 ratio. The mango gum showed the presence of amylose, alpha-arabinofuranosyl
      and beta-galactopyranosyl, respectively. The characterized mucilages and gum were
      individually formulated into nanoparticulate system using their complementarily
      charged polymer chitosan. The particles were observed to be spherical in shape in
      the range of 61.5-90 nm having zetapotential between 31 and 34 mV and PDI of
      0.097-0.241. The prepared nanoparticles were observed to be nonirritant and
      nontoxic in vitro and in vivo upto 2000 MUg/ml. Therefore, these mucilages and
      gum can be the alternatives of anionic polymers for the ocular drug delivery
      system.

PMID- 23952499
TI  - Adaptation-level theory, anchor theory, and the peak-shift phenomenon.
AB  - A study of the peak-shift phenomenon was conducted from the standpoint of
      adaptation level (AL) and anchor theory. 60 human Ss were divided into 6 groups -
      3 control and 3 experimental. During a training period each S lifted 2 weights of
      50 and 250, 100 and 300, or 150 and 350 gm. and was told to respond "same" or
      "different" by pressing the appropriate telegraph key during a forthcoming
      testing period, according to whether the weight he would lift was or was not one
      of the original two. Experimental Ss received discrimination training, in
      addition, with weights of 150, 200, and 250 gm. Following training, Ss were
      tested on 10 weights ranging from 50 to 500 gm. at 50-gm. intervals. The mean
      peaks for 4 of the 6 groups, 3 experimental and 1 control, were consistent with
      an AL-anchor interpretation. 

PMID- 23952498
TI  - Medical and psychological outcomes for young adults with Type 1 diabetes: no
      improvement despite recent advances in diabetes care.
AB  - AIM: To assess medical and psychological outcomes among young people with Type 1
      diabetes and to compare medical outcomes with a previous audit. METHODS: An
      observational study in two diabetes clinics for young adults (aged 16-21 years)
      in Sheffield, UK. Young people (n = 96: 81.4% response rate) with Type 1 diabetes
      (diagnosed > 6 months) completed measures of depressive symptoms, anxiety and
      disordered eating and consented for their medical records to be consulted.
      RESULTS: Mean HbA1c (86 +/- 23 mmol/mol; 10.0 +/- 2.1%); was comparable with that
      reported previously and considerably higher than recommended (< 58 mmol/mol or
      7.5%). Screening rates were improved and non-attendance was lower than previously
      reported, but levels of non-proliferative retinopathy have increased.
      Microvascular complications are present in 46.9% of those diagnosed more than 7
      years. Elevated levels of disordered eating were reported by 35.1%. Those scoring
      above cut-off levels for clinical anxiety (26.6%) and depression (10.9%) are
      comparable with other work with young people with Type 1 diabetes. CONCLUSIONS:
      Despite technological advances and improvements to delivery of care, HbA1c remain
      above recommended levels in a significant proportion of young people, many of
      whom already have microvascular complications. We need to learn from European
      centres who achieve better results, improve transition from paediatric care,
      integrate mental health support with diabetes care provision and take into
      account young people's views about clinic.

PMID- 23952500
TI  - Visual and proprioceptive determinants of space perception and movement.
AB  - The present study determined the relationship between perception of the upright
      in 2-dimensional space and movement accuracy. 161 female Ss were administered the
      Rod and Frame Test, and 30 Ss, whose scores indicated the greatest and least
      error in perceptual differentiation, were assigned to 2 experimental groups and
      measured on accuracy of postural pursuit tracking. The effects of direction of
      movement and visual field conditions on accuracy of performance were determined
      by a coordinate postural platform and hybrid computer methods. A direct
      relationship existed between perception of the vertical in space and accuracy of
      motor responses and that perceptual integration was affected by the direction of
      movement and the presence of a stable visual field. 

PMID- 23952501
TI  - Relationships as assessed by canonical correlation between perceptual-motor and
      intellectual abilities for pre-school and early elementary age children.
AB  - The relationship between 3 perceptual-motor tasks and 2 measures of academic
      achievement was assessed using canonical correlation. Ss were 113 children from
      kindergarten through third grade. A significant canonical correlation existed for
      the kindergarten, first, and second grade group, but the correlation for third
      graders was not statistically significant. There was a decreasing relationship
      between the perceptual-motor and intellectual domains as age increased. 

PMID- 23952502
TI  - Specificity and generality between various directions for reaction and movement
      times under choice stimulus conditions.
AB  - The degree of generality between forward, backward, left, and right directions
      was determined for RT and MT of the dominant hand and total body under choice
      stimulus conditions. Among 50 Ss, generality of directions for RT of the hand
      varied from 39 to 52%, while MT varied from 14 to 47%. Generality of RT for the
      total body varied from 36 to 55% between directions while MT varied from 6 to
      22%. The ability to react and move the dominant hand and total body under choice
      stimulus conditions appeared largely specific to the direction of the response. 

PMID- 23952503
TI  - Effect of achievement motivation and social environment on performance of a motor
      task.
AB  - The effect of achievement motivation and social environment on a motor task was
      investigated. 50 achieve-success Ss and 50 avoid-failure Ss (selected by the
      French Test of Insight and the Test Anxiety Questionnaire) practiced a modified
      shuffleboard task from which empirical probabilities of success for task
      performance were found for each S. In the performance phase Ss were randomly
      placed into one of 5 treatments - neutral, presence of others, interpersonal
      competition, interpersonal cooperation, interpersonal competition and intergroup
      competition. Ss were made aware of the scoring system and given 20 free-choice
      trials. Achieve-success Ss performed significantly better than avoid-failure Ss
      in the practice phase. No differences were found for achievement motivation in
      the performance phase. Social environment did not affect performance or interact
      with achievement level of Ss. 

PMID- 23952504
TI  - Facilitation of psychomotor learning by classically differentiated supplementary
      feedback cues.
AB  - 2 experiments on the control of psychomotor performance by classically
      differentiated supplementary feedback cues are reported. The first, conducted
      with 30 Ss as a replication of an earlier study, demonstrated again that
      otherwise ineffective supplementary cues can be transformed into highly effective
      regulators of psychomotor performance by differential conditioning procedures.
      The second, conducted with 78 Ss, showed that the effects of classically
      differentiated supplementary cues on tracking skill increased as a negatively
      accelerated function of the number of differentiation trials. Results were
      interpreted as exemplifying the operation of secondary drive and reinforcement
      principles, although the nonspecific transfer of arousal and/or warm-up effects
      were acknowledged as worthy alternatives. 

PMID- 23952505
TI  - Human selective learning as a joint function of response alternation and response
      availability.
AB  - 80 college Ss, divided equally between 2-choice and 4-choice tasks on the
      Selective Mathometer, practiced 20-unit S-R sequences for 30 trials by the
      correction method. Stimuli were 20 random dot patterns, all Ss being run under
      different alternating-response permutations. Each 2-choice key was assigned to 10
      different slides, each 4-choice key to 5 different slides. Half the 2-choice Ss
      practiced on adjacent keys, half on remote. Key spacing was not significant but
      response availability differences, as predicted, produced superior performance
      for the 2-choice task. Practice, availability, and their interaction were all
      significant, p < .001. Application of the equation Rp = a(i)(r(N)) to correct
      first choices over reinforced trials (N) resulted in typical Rp curve forms (fits
      > 98%) consistent with the rational parameters of asymptote (a), initial
      probability (i), and rate (r). Mean latencies (Rt) of correct responses and mean
      errors (R-) decreased as negatively-accelerated functions of N. All main effects
      and interactions for Rt and R- scores were significant, p <.001. 

PMID- 23952506
TI  - Stakeholders in opioid substitution treatment policy: similarities and
      differences in six European countries.
AB  - Based on the research papers within this special issue, this overview discusses
      similarities and differences in stakeholding in drug user opioid substitution
      treatment policy in Britain, Denmark, Italy, Austria, Poland, and Finland. It
      explores factors that have influenced stakeholder activity, including the
      importance of crisis, the impact of evidence, the availability of resources, the
      wider political context, the influence of moral frameworks and ideologies, and
      the pressure of external influences. The paper highlights the important
      differences in the emergence and evolution of stakeholder groups and in the
      political, cultural, and economic circumstances, which both constrain and enable
      their activities.

PMID- 23952507
TI  - Stakeholders' role in contemporary "substitute drug" prescribing policies in
      Italy.
AB  - This article, part of a comparative research project (WP2) funded by FP7 ALICE
      RAP, is based upon a review of literature and documents and 18 individual
      interviews with Italian national stakeholders (SHs) conducted in 2012. The goal
      was to identify the main shifts in opioid "substitution drug" treatment policies
      and understand the role played by different SHs during the last 30 years. The
      study confirms that opioid "substitution drug" treatment is a particularly
      suitable theme for improving knowledge in the field of SH analysis, even if
      results show that changes in policies are mainly due to external factors rather
      than to the action of SHs.

PMID- 23952508
TI  - Behind the scenes: the justifications for opioid maintenance treatment in
      Finland.
AB  - Opioid maintenance treatment (OMT) has been developed within drug dependency
      treatment in Finland over the last 20 years. This study, based on interviews with
      15 stakeholders and content analysis of 174 newspaper texts, draws on Boltanski
      and Thevenot's theory of justification to explore ways in which OMT has been
      justified and identifies the main actors contributing to its development.
      Multiple factors, involving different actors, have influenced the development
      process, reflecting the ethos of contemporary Finnish welfare and health policy.
      Currently, the main justifications for choosing OMT treatment seem to emerge from
      a neoliberal frame of understanding.

PMID- 23952509
TI  - Substitution treatment in the era of "recovery": An analysis of stakeholder roles
      and policy windows in Britain.
AB  - Based on documentary analyses and interviews with twenty key informants in 2012,
      this paper analyses the shift in British drugs policy towards "recovery" from the
      perspectives of major stakeholders. The processes involved in reopening the
      debate surrounding the role of substitution treatment and its re-emergence on to
      the policy agenda are examined. Drawing on Kingdon's work on agenda-setting, the
      ways in which methadone maintenance was challenged and defended by key
      stakeholders in the initial phase of policy development and the negotiation of a
      "recovery" focus as the organizing concept for British drugs policy are explored.
      Study limitations are noted. 

PMID- 23952510
TI  - Walking through mud; history of the Polish methadone maintenance treatment from
      its stakeholders' perspective.
AB  - This paper presents Polish methadone maintenance treatment (MMT) against the
      background of the dominant therapeutic community approach. The perspectives of
      various stakeholders-supporters and opponents-are examined as well as the
      barriers, facilitators, ideological conflicts, and financial interests
      influencing MMT policy and practice. In-depths interviews were carried out with
      18 major stakeholders around 2012, almost two decades after the first MMT was
      launched. The interviews shed light on stakeholders' inter- and intragroup
      conflicts as well as on their official and hidden agendas, but they also show the
      relevant wider international and national, economic, and political contexts.

PMID- 23952511
TI  - Shifts in opioid substitution treatment policy in Denmark from 2000-2011.
AB  - This article discusses how opioid substitution treatment policy has developed
      from 2000 to 2011 in Denmark. Empirically, it takes its point of departure in a
      stakeholder analysis including 17 qualitative interviews with stakeholders who
      have played important roles in this field. Analytically, it is inspired by
      Kingdon's concepts of agenda and policy window. Three major shifts are
      identified: a shift from psychosocial to medical thinking and practice, from an
      abstinence driven ideology to health care, and from perceptions of passive
      clients to user involvement. These shifts are discussed in relation to the legal
      context of substitute prescribing medicine.

PMID- 23952512
TI  - Deviance or innovation? Recent changes of drug substitution treatment policy in
      Austria.
AB  - This exploratory study investigates major changes in opioid substitution
      treatment during the last decade in Austria and identifies main interests groups
      and their interplay. Different levels of visibility of interest groups and
      variations in latency of interests contribute further to the complexity of the
      multilevel structure of interests and interest groups regarding substitute
      therapy issues. Austria's unique low threshold of substitution treatment was
      developed during the 1990s, and is based on the prescription of slow release
      morphine and on the high involvement of GPs. Opponents, becoming active during
      the new millennium, succeeded in tightening up legal regulations but failed to
      change treatment practice.

PMID- 23952513
TI  - Puzzling about opiate substitution therapy: a synopsis and commentary.

PMID- 23952514
TI  - Piecing together stakeholder puzzles-puzzling about (opioid substitute treatment-
      -OST) stakeholders and their pieces: a rambling point-of-view.
AB  - This point-of-view presentation explores "stakeholders" and "opioid substitute
      treatment," their dimensions, selected enabling necessary conditions to operate,
      or not, implications, and consequences from a range of selected perspectives. 

PMID- 23952515
TI  - Commentary on "Substitution treatment in the era of 'recovery': an analysis of
      stakeholder roles and policy windows in Britain".

PMID- 23952516
TI  - Commentary on Irmgard Eisenbach-Stangl, deviance or innovation? Recent changes of
      drug substitution treatment policy in Austria.

PMID- 23952517
TI  - Commentary on Jacek Moskalewicz and Marta Welbel, Walking through mud; history of
      the Polish methadone maintenance treatment from its stakeholders' perspective.

PMID- 23952518
TI  - Commentary on "Stakeholders' role in contemporary 'substitute drug' prescribing
      policies in Italy" by Franca Beccaria and Sara Rolando.

PMID- 23952519
TI  - Tracing the justifications of opioid maintenance treatment in Finland.

PMID- 23952520
TI  - Commentary on Vibeke Asmussen Frank, Bagga Bjerge, and Esben Houborg:
      Medicalization can be beneficial, but is no guarantee for user influence.

PMID- 23952522
TI  - Response to 'A systematic review and meta-regression analysis of aggression
      during first episode of psychosis'.

PMID- 23952523
TI  - Neurological disease in lambs associated with exposure to high environmental
      temperature and humidity.
AB  - BACKGROUND: We detected a pattern of lambs presenting with hyperthermia and
      neurological signs during the summer. OBJECTIVES: The main objectives of this
      study were to compare clinical findings and results of diagnostic testing and to
      identify a potential etiology. ANIMALS: Fifteen clinical cases of lambs less than
      12 months of age presenting with neurological signs, tachypnea, and hyperthermia
      over 4 summers. METHODS: Retrospective case series. Medical records were searched
      for lambs less than 12 months of age that presented with neurological signs
      including the following: kyphosis, pelvic limb hyperextension, treading of feet,
      muscle tremors and recumbency, and hyperthermia of greater than 104 degrees F. A
      grading system was established to describe severity of presenting neurological
      signs. Weather data were collected from weather stations near the farm of origin
      for 3 days prior to presentation. RESULTS: The lambs were from 7 flocks in
      central Texas. All cases occurred between July and September, with a median heat
      index of 90.5 for the 3 days before presentation. Complete blood count, serum
      chemistry, necropsy examination, rumen content, virology, brain MRI, liver
      copper, selenium, and vitamin E failed to identify a consistent etiology for the
      signs presented. The only common factor was high heat and humidity.
      Histopathological examination identified axonal degeneration and skeletal muscle
      necrosis in some lambs. CONCLUSIONS AND CLINICAL IMPORTANCE: These clinical cases
      appeared similar to the Australian disease humpyback and indicate that lambs
      exposed to high environmental temperatures and humidity might be at risk of
      developing the described clinical presentation.

PMID- 23952524
TI  - Estrogen therapy in gynecological cancer survivors.
AB  - Treatment of gynecological cancer has significant impact on a woman's quality of
      life because it commonly includes removal of the uterus and ovaries, both being
      the core of a woman's femininity, whilst irradiation and chemotherapy, be they as
      primary therapy or when indicated as postoperative adjuvant therapy, will lead to
      ablation of ovarian function if the ovaries had not been removed. This will lead
      to an acute onset of menopausal symptoms, which may be more debilitating than
      those occurring as a result of natural aging, and of which hot flushes, night
      sweats, insomnia, mood swings, vaginal dryness, decreased libido, malaise and a
      general feeling of apathy are the most common. About 25% of gynecological cancers
      will occur in pre- and perimenopausal women, a large percentage of whom will
      become menopausal as a result of their treatment. There are also the
      gynecological cancer survivors who are not rendered menopausal as a result of the
      treatment strategy but who will become menopausal because of natural aging.
      Concern among the medical attendants of these women is whether use of estrogen
      therapy or estrogen and progestogens for their menopausal symptoms will
      reactivate tumor deposits and therefore increase the rate of recurrence and, as a
      result, decrease overall survival among these women. Yet the data that are
      available do not support this concern. There are eight retrospective studies and
      only one randomized study that have analyzed outcome in endometrial cancer
      survivors who used hormone therapy after their surgery, whilst, among ovarian
      cancer survivors, there are four retrospective studies and one randomized study.
      The studies do suffer from small numbers and, although the studies pertaining to
      endometrial cancer analyze mostly women with early-stage disease, a number of the
      studies in both the endometrial and ovarian cancer survivors do have a sizeable
      follow-up. These studies seem to support that estrogen therapy after the
      treatment for gynecological cancer does not impact negatively on outcome in
      endometrial and ovarian cancer survivors and that estrogen therapy can be
      considered as a plausible therapeutic option in survivors who are debilitated by
      their menopausal symptoms. It is prudent not to offer estrogen therapy to
      survivors of endometrial stromal sarcoma and women with granulosa cell tumors of
      the ovaries. Vulval, vaginal and cervical cancers are not considered hormone
      dependent and therefore estrogen therapy can be given.

PMID- 23952525
TI  - Benzannulation via the reaction of ynamides and vinylketenes. application to the
      synthesis of highly substituted indoles.
AB  - A two-stage "tandem strategy" for the synthesis of indoles with a high level of
      substitution on the six-membered ring is described. Benzannulation based on the
      reaction of cyclobutenones with ynamides proceeds via a cascade of four
      pericyclic reactions to produce multiply substituted aniline derivatives in which
      the position ortho to the nitrogen can bear a wide range of functionalized
      substituents. In the second stage of the tandem strategy, highly substituted
      indoles are generated via acid-, base-, and palladium-catalyzed cyclization and
      annulation processes. 

PMID- 23952526
TI  - Access to Medicare-funded annual comprehensive health assessments for rural
      people with intellectual disability.
AB  - INTRODUCTION: People with intellectual disability (ID) comprise 2-3% of the
      Australian population. They mostly rely on their GP for primary health care. In
      rural areas where there are issues with health workforce shortages, there is a
      risk that people with ID may not get timely access to primary care or may not be
      aware of the range of healthcare services available to support them.
      Internationally, research has shown that regular health assessments are
      beneficial for people with ID. Annual comprehensive health assessments (ACHAs)
      have been shown to result in increased detection of medical conditions and could
      assist in reducing the gap in mortality between people with ID and the broader
      population. <b> </b>In Australia, people with ID have been eligible to access
      ACHAs under Medicare since 2007.<b> </b>These provide for a regular review of the
      person's physical, psychological and social functioning. This study explored the
      extent to which rural people with ID were accessing these ACHAs, and factors
      which affected their access to ACHAs. METHODS: In this qualitative study in-depth
      interviews were conducted with 18 participants including people with ID,
      carers/support workers and rural doctors. Interviews were then coded and analysed
      for themes. RESULTS: Seven themes were identified: (1) healthcare barriers in
      rural areas; (2) cohesion of rural communities; (3) the way rural doctors
      practice; (4) lack of knowledge/understanding; (5) venturing into new territory;
      (6) the role of the practice nurse; and (7) the health communication triangle.
      CONCLUSION: Despite the well-known problems of lack of services and distance to
      specialists in rural Australia, there are compensatory factors which were
      perceived as improving the wellbeing of people with ID, such as increased social
      cohesion and community connectedness. More education is needed to ensure that the
      rationale for ACHAs for people with ID is understood and that doctors feel
      confident to use them. The number of Medicare reforms implemented in a relatively
      short period presented change-management challenges for rural practices with
      rural workforce pressures. The role of the carer/support worker is crucial in the
      health assessment process and can improve the transfer of information about a
      client with ID between the disability and health sectors and within the health
      sector.

PMID- 23952527
TI  - Experimental and DFT characterization of metal-to-ligand charge-transfer excited
      states of (rutheniumammine)(monodentate aromatic ligand) chromophores.
AB  - The heretofore unknown emission properties of the metal-to-ligand charge-transfer
      (MLCT) excited states of several complexes with (ruthenium)(monodentate aromatic
      ligand, MDA) chromophores are given. Emission spectra and lifetimes in 77 K
      glasses are reported for several monometallic complexes of the type [Ru(NH3)(5
      n)(L)(n)(MDA)](2+) and two bimetallic pyrazine (pz)-bridged [{Ru(NH3)(4
      n)(L)(n)}2pz](4+) complexes (L = pz, pyridine, or a multipyridine ligand; MDA =
      pz or a substituted pyridine, Y-py). The emission maxima occur in the visible and
      near-IR spectral regions and have much more poorly resolved vibronic sidebands
      than do related complexes with Ru-bpy chromophores, and the excited-state
      lifetimes are characteristic of Ru-bpy MLCT excited states in this energy range.
      The emission yields of trans-[Ru(NH3)4(MDA)(pz)](2+) (MDA = py or pz) are less
      than 0.2%, and combined with the other observations, this implies that most of
      the excited-state quenching occurs in high-energy excited states whose population
      precedes that of the lowest-energy (3)MLCT excited state. The pz-bridged,
      bimetallic complexes have mixed-valence excited states, and they absorb and emit
      at lower energies than their monometallic analogues do.

PMID- 23952528
TI  - Hyper-elastic modelling of intervertebral disc polyurethane implant.
AB  - Artificial materials including various kinds of polymers like polyurethanes are
      more and more widely used in different branches of science and also in biomedical
      engineering. The paper presents the process of creating a constitutive equation
      for a polyurethane nanocomposite which is considered to be hyper-elastic. The
      constitutive modelling was conducted within the range of application of the
      material as one of the components of lumbar intervertebral disc prosthesis. In
      the paper, the biomechanics of the lumbar spine and the most frequently applied
      intervertebral disc prostheses are described. Also a polyurethane nanocomposite
      as a new material to be applied in prostheses is presented. The way of
      formulating a constitutive equation by means of mathematical formulae is
      described. Four various hyper-elastic potential functions are considered, i.e.,
      Ogden, Neo-Hookean, Yeoh and Mooney-Rivlin. On the basis of monotonic compression
      tests the best hyper-elastic model for the material considered was chosen and
      hyper-elastic constants were calibrated. Finally, the constitutive model was
      validated on the basis of FE analysis. The paper ends with a conclusion and
      presentation of further plans of research directed towards the development of a
      constitutive equation and its application in computer simulations by means of the
      finite element method. 

PMID- 23952529
TI  - Screening for dementia--is it a no brainer?
AB  - As people are living longer, dementia is becoming a significant issue for
      society. Dementia is now recognised as a major concern in society, and the
      numbers of people estimated to have dementia in the UK population appear to have
      stabilised at around 700,000 . Globally, 35.6 million people are estimated to
      meet criteria for dementia, a number predicted to double every 20 years . Given
      the absence of treatments that significantly alter the natural history of the
      clinical syndrome of dementia, there has been increased emphasis on early
      diagnosis, with research exploring assessment tools and biomarkers that might
      predict with certainty a particular clinical outcome. At the same time, there has
      been pressure to focus on biomedical profiles, which assume a very close link
      between the pathobiology and the manifest clinical syndrome. 

PMID- 23952530
TI  - Impacts of chloramine-T treatment on antioxidant enzyme activities and
      genotoxicity in rainbow trout, Oncorhynchus mykiss (Walbaum).
AB  - Juvenile rainbow trout Oncorhynchus mykiss (Walbaum) were exposed to therapeutic,
      and higher concentrations of chloramine-T (Cl-T) to assess the effects of this
      chemical on the antioxidant enzyme system and genetic structure. Red blood cells
      acetylcholinesterase, ?-aminolevulinic acid dehydratase, paraoxonase and liver
      glutathione S-transferase activity were increased at 10 and 20 mg L(-1) Cl-T
      exposed fish, while they were decreased at 30 mg L(-1) Cl-T-exposed fish. On the
      other hand, liver catalase activity and liver protein levels increased at 10 mg
      L(-1) and decreased at 20 and 30 mg L(-1) concentrations of Cl-T. Liver super
      oxide dismutase activity decreased at 10 mg L(-1) and 20 mg L(-1) Cl-T and
      increased at 30 mg L(-1) of Cl-T. Compared to control, comet assay indicated that
      Cl-T did not cause significant DNA damage to red blood cells of the fish. Results
      indicate that 10 or 20 mg L(-1) Cl-T can be safely used to prevent or treat
      external parasitic and bacterial infection of rainbow trout.

PMID- 23952531
TI  - Oxidative stress in acute pancreatitis: lost in translation?
AB  - Oxidative stress has been implicated in the pathogenesis of acute pancreatitis, a
      severe and debilitating inflammation of the pancreas that carries a significant
      mortality, and which imposes a considerable financial burden on the health system
      due to patient care. Although extensive efforts have been directed towards the
      elucidation of critical underlying mechanisms and the identification of novel
      therapeutic targets, the disease remains without a specific therapy. In
      experimental animal models of acute pancreatitis, increased oxidative stress and
      decreased antioxidant defences have been observed, changes also detected in
      patients clinically. However, despite the promise of studies evaluating the
      effects of antioxidants in these model systems, translation to the clinic has
      thus far been disappointing. This may reflect many factors involved in the design
      of both preclinical and clinical evaluations of antioxidant therapy, not least
      the fact that most experimental studies have focussed on pre-treatment rather
      than post-injury assessment. This review has examined evidence relating to the
      involvement of oxidative stress in the pathophysiology of acute pancreatitis,
      focussing on experimental models and the clinical experience, including the
      experimental techniques employed and potential of antioxidant therapy.

PMID- 23952532
TI  - Gene networks controlling Arabidopsis thaliana flower development.
AB  - The formation of flowers is one of the main models for studying the regulatory
      mechanisms that underlie plant development and evolution. Over the past three
      decades, extensive genetic and molecular analyses have led to the identification
      of a large number of key floral regulators and to detailed insights into how they
      control flower morphogenesis. In recent years, genome-wide approaches have been
      applied to obtaining a global view of the gene regulatory networks underlying
      flower formation. Furthermore, mathematical models have been developed that can
      simulate certain aspects of this process and drive further experimentation. Here,
      we review some of the main findings made in the field of Arabidopsis thaliana
      flower development, with an emphasis on recent advances. In particular, we
      discuss the activities of the floral organ identity factors, which are pivotal
      for the specification of the different types of floral organs, and explore the
      experimental avenues that may elucidate the molecular mechanisms and gene
      expression programs through which these master regulators of flower development
      act.

PMID- 23952534
TI  - The future in clinical genetics: affective forecasting biases in patient and
      clinician decision making.
AB  - When clinicians facilitate and patients make decisions about predictive genetic
      testing, they often base their choices on the predicted emotional consequences of
      positive and negative test results. Research from psychology and decision making
      suggests that such predictions may often be biased. Work on affective forecasting
      predicting one's future emotional states-shows that people tend to overestimate
      the impact of (especially negative) emotional events on their well-being; a
      phenomenon termed the impact bias. In this article, we review the causes and
      consequences of the impact bias in medical decision making, with a focus on
      applying such findings to predictive testing in clinical genetics. We also
      recommend strategies for reducing the impact bias and consider the ethical and
      practical implications of doing so. 

PMID- 23952533
TI  - Longitudinal association between serum urate and subclinical atherosclerosis: the
      Coronary Artery Risk Development in Young Adults (CARDIA) study.
AB  - OBJECTIVE: The aim of the present study was to determine whether serum urate
      (sUA) concentration is positively associated with subclinical atherosclerosis,
      independent of body mass index (BMI), amongst generally healthy adults. DESIGN
      AND SETTING: The CARDIA study followed 5115 Black and White individuals aged 18
      30 years in 1985-1986 (year 0). Subclinical atherosclerosis comprised coronary
      artery calcified plaque (CAC; years 15, 20 and 25), and maximum common carotid
      intima-media thickness (IMT; year 20). sUA (years 0, 10, 15 and 20) was modelled
      as gender-specific quartiles that were pooled. Discrete-time hazard regressions
      and generalized linear regressions were used for analyses. RESULTS: Mean sUA
      concentration was lower in women than in men and increased with age. Adjusting
      for demographic and lifestyle factors, the highest versus lowest quartile of sUA
      at year 0 was associated with a 44% [95% confidence interval (CI) 20%, 73%]
      greater risk of CAC progression from years 15 to 25 (Ptrend  < 0.001), which was
      attenuated by adjustment for BMI at year 0 (Ptrend  = 0.45). A stronger
      association was found between sUA at year 15 and CAC progression at year 20 or 25
      (hazard ratio 2.07, 95% CI 1.66, 2.58 for the highest versus lowest sUA quartile
      Ptrend  < 0.001), which was attenuated, but remained significant with additional
      adjustment for BMI at year 15 (Ptrend  = 0.01). A greater increment in sUA
      concentration from year 0 to year 15, independent of change in BMI, was related
      to a higher risk of CAC progression (Ptrend  < 0.001). Similar associations were
      found between sUA and IMT, but only in men. CONCLUSION: sUA may be an early
      biomarker for subclinical atherosclerosis in young adults; starting in early
      middle age, sUA predicts subclinical atherosclerosis independently of BMI.

PMID- 23952535
TI  - Spatial memory and learning performance and its relationship to protein synthesis
      of Swiss albino mice exposed to 10 GHz microwaves.
AB  - PURPOSE: To study the possible role of microwave (MW) exposure on spatial memory
      of Swiss albino mice and its relationship to protein concentration in whole
      brain. MATERIALS AND METHODS: Mice were exposed to 10 GHz (Giga Hertz) microwaves
      with the power density of 0.25 mW/cm(2) (milliwatt per centimeter square) with
      average whole body specific absorption rate (SAR) 0.1790 W/kg daily for 2 hours
      per day (h/day) for 30 days. After exposure mice were tested for spatial memory
      performance using Morris water maze test (MWT). For this purpose mice (6-8 weeks
      old) were divided into two groups: (i) Sham exposed, and (ii) microwaves exposed.
      After initial training for two days, MWT was performed for another 6 days.
      Protein was estimated 48 h after exposure and immediately after completion of
      MWT. RESULTS: Both sham-exposed and microwaves-exposed animals showed a
      significant decrease in escape time with training. Microwaves-exposed animals had
      statistically significant higher mean latency to reach the target quadrant
      compared to sham exposed. A concurrent decrease in protein levels was estimated
      in whole brain of the exposed mice compared to sham-exposed mice. CONCLUSIONS: It
      can be concluded from the current study that exposure to microwave radiation
      caused decrements in the ability of mice to learn the special memory task, this
      may be due to simultaneous decrease in protein levels in the brain of mice.

PMID- 23952536
TI  - Anti-c-MET Nanobody - a new potential drug in multiple myeloma treatment.
AB  - BACKGROUND: c-MET is the tyrosine kinase receptor of the hepatocyte growth factor
      (HGF). HGF-c-MET signaling is involved in many human malignancies, including
      multiple myeloma (MM). Recently, multiple agents have been developed directed to
      interfere at different levels in HGF-c-MET signaling pathway. Nanobodies are
      therapeutic proteins based on the smallest functional fragments of heavy-chain
      only antibodies. In this study, we wanted to determine the anticancer effect of a
      novel anti-c-MET Nanobody in MM. METHODS: We examined the effects of an anti-c
      MET Nanobody on thymidine incorporation, migration, adhesion of MM cells, and
      osteoblastogenesis in vitro. Furthermore, we investigated the effects of the
      Nanobody on HGF-dependent c-MET signaling by Western blotting. RESULTS: We show
      that the anti-c-MET Nanobody effectively inhibited thymidine incorporation of
      ANBL-6 MM cells via inhibition of an HGF autocrine growth loop and thymidine
      incorporation in INA-6 MM cells induced by exogenous HGF. HGF-induced migration
      and adhesion of INA-6 were completely and specifically blocked by the Nanobody.
      Furthermore, the Nanobody abolished the inhibiting effect of HGF on bone
      morphogenetic protein-2-induced alkaline phosphatase activity and the
      mineralization of human mesenchymal stem cells. Finally, we show that the
      Nanobody reduced phosphorylation of tyrosine residues in c-MET, MAPK, and Akt. We
      also compared the Nanobody with anti-c-MET monoclonal antibodies and revealed the
      similar or better effect. CONCLUSIONS: The anti-c-MET Nanobody inhibited MM cell
      migration, thymidine incorporation, and adhesion, and blocked the HGF-mediated
      inhibition of osteoblastogenesis. The anti-c-MET Nanobody might represent a novel
      therapeutic agent in the treatment of MM and other cancers driven by HGF-c-MET
      signaling.

PMID- 23952538
TI  - Snapshots reflecting the lives of siblings of children with autism spectrum
      disorders.
AB  - BACKGROUND: Past research focused on the effects of raising a child with autism
      spectrum disorder on families. However, most research examined parents'
      perspectives rather than siblings' perspectives. Therefore, the purpose of this
      qualitative descriptive design was to use photo elicitation to capture
      perspectives of siblings living with a child with autism spectrum disorder.
      METHODS: Fourteen siblings (nine male) of 13 children with autism spectrum
      disorder received disposable cameras with 24-27 colour exposures, and were asked
      to photograph what was important to them within 2 weeks. After developing
      snapshots, investigators interviewed siblings about their photographs, and used
      open, axial and selective coding to determine photograph categories and
      subcategories. RESULTS: Two major categories were found: people (family members,
      non-family members) and non-people (personal items/objects, animals, buildings,
      scenery). Interviews about photographs reflected experiences siblings had with
      people/non-people in the snapshots and their normal everyday activities. Most
      photographs revealed family life and activities any sibling would experience
      whether or not they lived in a family raising a child with autism spectrum
      disorder. CONCLUSIONS: Photo elicitation facilitates communication between
      children and health-care professionals, and provides information about living
      with a child with autism spectrum disorder from the sibling's perspective. This
      information contributes to our knowledge base and allows development of specific
      intervention plans for siblings of these children.

PMID- 23952537
TI  - Carboxyl group of Glu113 is required for stabilization of the diferrous and bis
      Fe(IV) states of MauG.
AB  - The diheme enzyme MauG catalyzes a six-electron oxidation required for post
      translational modification of a precursor of methylamine dehydrogenase (preMADH)
      to complete the biosynthesis of its protein-derived tryptophan tryptophylquinone
      (TTQ) cofactor. Crystallographic studies have implicated Glu113 in the formation
      of the bis-Fe(IV) state of MauG, in which one heme is Fe(IV)?O and the other is
      Fe(IV) with His-Tyr axial ligation. An E113Q mutation had no effect on the
      structure of MauG but significantly altered its redox properties. E113Q MauG
      could not be converted to the diferrous state by reduction with dithionite but
      was only reduced to a mixed valence Fe(II)/Fe(III) state, which is never observed
      in wild-type (WT) MauG. Addition of H2O2 to E113Q MauG generated a high valence
      state that formed more slowly and was less stable than the bis-Fe(IV) state of WT
      MauG. E113Q MauG exhibited no detectable TTQ biosynthesis activity in a steady
      state assay with preMADH as the substrate. It did catalyze the steady-state
      oxidation of quinol MADH to the quinone, but 1000-fold less efficiently than WT
      MauG. Addition of H2O2 to a crystal of the E113Q MauG-preMADH complex resulted in
      partial synthesis of TTQ. Extended exposure of these crystals to H2O2 resulted in
      hydroxylation of Pro107 in the distal pocket of the high-spin heme. It is
      concluded that the loss of the carboxylic group of Glu113 disrupts the redox
      cooperativity between hemes that allows rapid formation of the diferrous state
      and alters the distribution of high-valence species that participate in charge
      resonance stabilization of the bis-Fe(IV) redox state. 

PMID- 23952539
TI  - Effects of high-dose radiotherapy on implantable cardioverter defibrillators: an
      in vivo porcine study.
AB  - INTRODUCTION: Although the effects of radiotherapy (RT) on implantable
      cardioverter defibrillators (ICDs) have been studied in vitro, and some
      information has been gathered from case reports and series, no in vivo
      experiments have previously been performed. METHODS: In vivo effects of photon RT
      applied directly to five modern ICD generators from different manufacturers
      implanted in pigs were studied. The devices were interrogated between and after
      increasing doses of ionizing radiation. Afterwards, the shock function was
      tested. RESULTS: All ICDs withstood fractionated irradiations with a cumulative
      dose of 18.5 gray (Gy) of 6 megavolt (MV) photons and 18.5 Gy of 18 MV photons
      and were still fully functional. Especially, no oversense was recorded. Induced
      ventricular fibrillation was detected and treated properly by shock therapy in
      all cases. However, one of the ICDs converted to back-up mode later the same
      night. CONCLUSION: The animal model is feasible for investigating RT effects on
      implanted cardiac devices. During irradiations with 37 Gy, one recoverable
      malfunction was present in the tested devices. Additional animal studies could
      provide supplementary evidence for treating ICD patients, including
      recommendations for reprogramming of the ICD during RT and avoidance of
      relocating the device.

PMID- 23952540
TI  - An occupational therapy experience in ecuador.
AB  - This paper describes the experiences of the author, her husband and a physical
      therapist who travelled to Ecuador in 1989 for three months to volunteer in their
      professions. It highlights aspects of health care in that country and of
      occupational therapy education and practice. It focuses on their teaching
      experiences in various settings and on their participation in the development of
      a daily living skills program for the disabled. 

PMID- 23952541
TI  - A perspective on consulting in guatemala.
AB  - Attempting to offer short-term help in a center for disabled, delayed and
      nutritionally deprived children in Antigua Guatemala was quite a learning
      experience. Good intentions and conventional Northern approaches often collided
      with reality, providing the author with perhaps as many learning experiences as
      she was able to provide to the center. 

PMID- 23952542
TI  - Sensory integration in Finland.
AB  - This article describes the development and organization of a sensory integration
      training course given in Finland. Facts that impact on the success of
      international health education are discussed in relation to thc model used for
      this course. In addition, cultural differences (e.g, language, customs, health
      care, and education systems) are discussed as they relate to this teaching
      experlence and to occupational therapy practice in Finland. The summary
      highlights examples of how teaching and/or working in another culture can impact
      on professional development. 

PMID- 23952543
TI  - Schizophrenia:.
AB  - In Zanzibar, as in many "third world" places, there are two health care systems,
      one traditional and the other "European." Among the Swahili people of East Africa
      spirits are believed to be the cause of disturbed behavior or "madness." Data and
      observations gathered during one year of mental health practice in Zanzibar and
      over many years of practice in the U.S. are compared to examine how cultural
      values shape beliefs, practices and attitudes related to "madness." Implications
      for occupational therapy theory and practice are drawn. 

PMID- 23952544
TI  - Evaluating the developmental skills of cambodian orphans.
AB  - The author found the experience of evaluating orphans in Cambodia different from
      her expectations and it has changed her attitudes toward education and medicine.
      She suggests that all prospective orphans be evaluated by a therapist in order to
      anticipate the severity of potential problems. She also feels that occupational
      therapists must take an active role in affecting the lives of people in third
      world countries. The author discusses how her experience is shaping her
      professional goals since she returned from Cambodia. 

PMID- 23952545
TI  - Training in a Foreign Land That is Home.
AB  - The author describes her pediatric Level 11 fieldwork experience in Southeast
      Alaska. She discusses her professional development during this time, and some of
      the differences between practice in Southeast Alaska and Seattle, Washington. 

PMID- 23952546
TI  - Of related interest.
AB  - No abstract available for this article. 

PMID- 23952547
TI  - Continuing discussion on:.
AB  - No abstract available for this article. 

PMID- 23952548
TI  - An ernest response to roberts' comments.
AB  - No abstract available for this article. 

PMID- 23952550
TI  - Preface.
AB  - No abstract available for this article. 

PMID- 23952551
TI  - Hepatotoxic potential of therapeutic oligonucleotides can be predicted from their
      sequence and modification pattern.
AB  - Antisense oligonucleotides that recruit RNase H and thereby cleave complementary
      messenger RNAs are being developed as therapeutics. Dose-dependent hepatic
      changes associated with hepatocyte necrosis and increases in serum alanine
      aminotransferase levels have been observed after treatment with certain
      oligonucleotides. Although general mechanisms for drug-induced hepatic injury are
      known, the characteristics of oligonucleotides that determine their hepatotoxic
      potential are not well understood. Here, we present a comprehensive analysis of
      the hepatotoxic potential of locked nucleic acid-modified oligonucleotides in
      mice. We developed a random forests classifier, in which oligonucleotides are
      regarded as being composed of dinucleotide units, which distinguished between 206
      oligonucleotides with high and low hepatotoxic potential with 80% accuracy as
      estimated by out-of-bag validation. In a validation set, 17 out of 23
      oligonucleotides were correctly predicted (74% accuracy). In isolation, some
      dinucleotide units increase, and others decrease, the hepatotoxic potential of
      the oligonucleotides within which they are found. However, a complex interplay
      between all parts of an oligonucleotide can influence the hepatotoxic potential.
      Using the classifier, we demonstrate how an oligonucleotide with otherwise high
      hepatotoxic potential can be efficiently redesigned to abate hepatotoxic
      potential. These insights establish analysis of sequence and modification
      patterns as a powerful tool in the preclinical discovery process for
      oligonucleotide-based medicines. 

PMID- 23952552
TI  - Severe obesity and diabetes self-care attitudes, behaviours and burden:
      implications for weight management from a matched case-controlled study. Results
      from Diabetes MILES--Australia.
AB  - AIMS: To investigate whether diabetes self-care attitudes, behaviours and
      perceived burden, particularly related to weight management, diet and physical
      activity, differ between adults with Type 2 diabetes who are severely obese and
      matched non-severely obese control subjects. METHODS: The 1795 respondents to the
      Diabetes MILES--Australia national survey had Type 2 diabetes and reported height
      and weight data, enabling BMI calculation: 530 (30%) were severely obese (BMI >=
      35 kg/m(2); median BMI = 41.6 kg/m(2)) and these were matched with 530 control
      subjects (BMI < 35 kg/m(2); median BMI = 28.2 kg/m(2)). Diabetes self-care
      behaviours, attitudes and burden were measured with the Diabetes Self-Care
      Inventory-Revised. Within-group and between-group trends were examined. RESULTS:
      The group with BMI >= 35 kg/m(2) was less likely to achieve healthy diet and
      exercise targets, placed less importance on diet and exercise recommendations,
      and found the burden of diet and exercise recommendations to be greater than the
      group with BMI < 35 kg/m(2). The group with BMI >= 35 kg/m(2) was more likely to
      be actively trying to lose weight, but found weight control a greater burden.
      These issues accentuated with increasing obesity and were greatest in those with
      BMI > 45 kg/m(2). There were no between-group differences in other aspects of
      diabetes self-care: self-monitoring of blood glucose, use of medications and
      smoking. Moderate-to-severe symptoms of depression were independently associated
      with reduced likelihood of healthy diet and physical activity, and with greater
      burden associated with diet, physical activity and weight management.
      CONCLUSIONS: Severely obese people with diabetes demonstrated self-care
      attitudes, behaviours and burdens that infer barriers to weight loss. However,
      other important diabetes self-care behaviours are supported equally by severely
      obese and non-severely obese individuals.

PMID- 23952553
TI  - Assessment of coagulation and potential biochemical markers for
      hypercoagulability in canine hyperadrenocorticism.
AB  - BACKGROUND: Anecdotal accounts and limited research suggest that dogs with
      spontaneous hyperadrenocorticism (HAC) are at risk of developing thromboembolic
      complications. Detailed description of coagulation status and identification of
      subsets of dogs at greatest risk would impact therapeutic recommendations for
      these patients. HYPOTHESIS/OBJECTIVES:  HYPOTHESIS: A subset of dogs with HAC
      will have a hypercoagulable tendency as identified by increased procoagulant
      activity, decreased fibrinolysis, or both. Objective 1: To document the existence
      of this hypercoagulable tendency in HAC dogs using assays of individual
      coagulation factors, fibrinolytic activity, and systemic coagulation. Objective
      2: To evaluate clinical and biochemical markers in HAC dogs to identify a subset
      of HAC patients at increased risk of this hypercoagulable tendency. ANIMALS:
      Seventeen dogs newly diagnosed with HAC. METHODS: Prospective study. Medical
      history, physical examination findings, routine diagnostic tests, and
      comprehensive coagulation testing were performed at the time of HAC diagnosis.
      Coagulation parameters were assessed individually and as panels for each dog.
      Historical and clinical variables were correlated with coagulation parameters to
      identify risk factors. RESULTS: The majority (88.2%) of HAC dogs exhibited a
      hypercoagulable tendency. Abnormalities in 1 coagulation assay did not predict
      abnormalities in others. Duration of clinical signs of HAC did not predict
      hypercoagulability. Comorbid conditions or abnormal clinicopathologic parameters
      that predicted hypercoagulability were not identified. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Although HAC dogs may demonstrate a hypercoagulable tendency
      individually and as a group, comorbid conditions or biochemical variables that
      would predict more severe coagulation abnormalities were not identified.

PMID- 23952554
TI  - The role of visual cues in movement control and motor memory.
AB  - 3 groups of 12 Ss performed an index finger letter-writing task with visual
      information but without kinesthetic cues (+V-K), followed immediately by
      repeating the same letters without vision (-V-K). All groups performed 6 test
      trials of + V-K, then -V-K writing. Group 1 had no experience with the task prior
      to the test trials, Group 2 practiced the letters without vision with kinesthetic
      cues (-V+K), while Group 3 had visual and kinesthetic practice (+V+K). Visual
      cues efficiently guided performance in the absence of kinesthesis, and visual
      memory traces had a marked reinforcing effect. Further, learned reliance on
      kinesthetic cues was present even in +V-K performance, but reliance on visual
      cues did not develop. 

PMID- 23952555
TI  - The case against learning and forgetting scores.
AB  - The frequent use of gain or loss scores as measures of the amount of learning and
      forgetting in motor skills was discussed. Learning is redefined as a gain in
      habit strength (forgetting a loss), with habit being a hypothetical construct
      representing the internal state which is learning. The use of gain scores is
      discussed in terms of the "physicalism-subjectivism dilemma," concerning the fact
      that the relationship between gains in performance and gains in habit strength
      (learning) is not known causing meaningless interpretations about the amount of
      learning. The dilemma has great consequences in studies of individual differences
      in learning, but is important in experimental designs as well. Some possible
      solutions to the dilemma are discussed. 

PMID- 23952556
TI  - The effects of personality and ability on speed of decisions regarding the
      directional aspects of ball flight.
AB  - A choice reaction time test (CRT) and a task which involved judging the
      directional aspects of bail flight (BFT) were administered to 3 groups defined as
      high ability table tennis players (N = 13), average ability table tennis players
      (N = 18), and non-games players (N = 15). An analysis of the results of the BFT
      task in terms of personality (Eysenck's extraversion/introversion and neuroticism
      dimensions) failed to show any significant differences although significant
      differences were found between the ability groups in both the CRT and BFT tasks.
      The relationship between Ss' times for the 2 tasks was significant for the non
      games players and average ability table tennis players but not for the high
      ability table tennis players. Possible explanations for this latter result are
      suggested. 

PMID- 23952557
TI  - The effects of the mere presence of coactors on learning a motor skill.
AB  - This study determined the effects of the mere presence of 1 or 3 coactors on the
      acquisition of a novel motor skill. The performance of tetrads was significantly
      inferior to that of Ss alone and in dyads. The findings were discussed in terms
      of Zajonc's social facilitation hypothesis and recent developments thereof. 

PMID- 23952558
TI  - Gross motor performance in minimally brain injured children.
AB  - As a pre-requisite to curriculum development, the characteristics of the gross
      motor performance of special education classes of minimally brain injured boys
      and girls were described. In general, age changes in mean performance were
      linear, the scores of the boys being the superior. The level of performance very
      closely resembled that of comparison groups of educable mentally retarded
      children from the same school districts. 

PMID- 23952559
TI  - Effect of age, feedback, and practice on ability to respond within a fixed time
      interval.
AB  - Accuracy and consistency of response within a fixed time interval as a function
      of age and practice with feedback were investigated. The task was pressing a
      telegraph key within a given interval following the last release of the key. The
      interval was empty and was pre-set at 2.75-3.24 sec. One piece of candy was
      dispensed for each inter-response-interval (IRI) which was correct. For both
      number of correct IRIs and SD of IRI significant effects were noted for Age,
      Feedback, and Practice. In addition, for SD of IRI, Age and Feedback interacted
      significantly. Magnitudinal feedback appeared to be more confusing than either
      specific or directional feedback and resulted in less improvement than either of
      the latter. 

PMID- 23952560
TI  - Closed-loop control of a ballistic response.
AB  - The ability of Ss to maintain or improve the accuracy of force of a hammer strike
      in the presence or absence of KR was examined. 70 trials on a 10% KR schedule
      provided opportunities to examine this ability. Initial improvements were
      dependent on KR. More gradual improvements continued but could not separately be
      attributed to KR or non-KR processes. Although indications of subjective
      reinforcement were not significant, the process remained a plausible complement
      to external KR. 

PMID- 23952561
TI  - Prevalence of Obstructive Sleep Apnea After Orticochea Pharyngoplasty for
      Velopharyngeal Insufficiency Management.
AB  - BACKGROUND AND PURPOSE: The aim of this study is to describe the prevalence of
      obstructive sleep apnea (OSA) and its level of severity associated with
      Orticochea pharyngoplasty in patients with velopharyngeal insufficiency after at
      least 1 year of the surgical procedure. DESIGN: Case series prospective
      descriptive study. MAIN OUTCOME MEASURES: At FISULAB, a rehabilitation center for
      patients with cleft palate, we studied 37 patients who were treated elsewhere
      with Orticochea pharyngoplasty for velopharyngeal insufficiency; these patients
      may or may not have had clinical symptoms related to OSA. All participants
      underwent a polysomnography sleep study, which was also done in different
      institutions. We applied the Epworth Sleepiness Scales during the clinical
      investigation because it is an effective instrument used to measure average
      daytime sleepiness. Another questionnaire to identify cases of OSA was used.
      Among other variables studied, the apnea/hypopnea index was the main outcome,
      while age and type of cleft were secondary variables. RESULTS: From 37 patients
      who were studied (100%), we obtained the following results: normal apnea/hypopnea
      index: seven patients (18.9%); mild apnea/hypopnea index: 14 patients (37.8%);
      moderate apnea/hypopnea index: eight patients (21.6%); and severe apnea/hypopnea
      index: eight patients (21.6%). CONCLUSIONS: In this study, we found that more
      than three quarters (81%) of the patients who were treated for velopharyngeal
      insufficiency with Orticochea pharyngoplasty presented obstructive sleep apnea
      when analyzing the apnea/hypopnea index in the polysomnography sleep study.

PMID- 23952562
TI  - Effect of Recombinant Human Bone Morphogenetic Protein-2 and Adipose Tissue
      Derived Stem Cell on New Bone Formation in High-Speed Distraction Osteogenesis.
AB  - PURPOSE: The effects of recombinant human bone morphogenetic protein-2 (rhBMP-2)
      and osteogenically differentiated adipose tissue-derived stem cells (ADSC) on new
      bone formation in high-speed distraction osteogenesis of adult rabbit cranium
      were investigated. MATERIALS AND METHODS: A total of 41 adult rabbits were used
      in the study. Distraction began after a 5-day latency period at a rate of 1.5 mm
      twice a day until 10-mm length gain was obtained both in the control group, where
      a bone defect was induced, and in the experimental group, in which ADSC (group
      A), rhBMP-2 (group B), or both (group C) were injected in the distraction gap
      after distraction. At 4, 8, and 12 weeks after distraction, computed tomography
      analysis was done to determine the bone defect dimension and bone mineral density
      (BMD), while histologic examination was also done to calculate bone formation
      ratio. RESULTS: Bone defect dimension significantly decreased in groups B and C,
      compared with the control group, at 4 and 12 weeks after distraction. BMD was
      significantly increased in groups B and C at 4 weeks. On histologic examination,
      bone formation ratio was significantly increased in group C only at 12 weeks.
      CONCLUSION: This study suggests that the use of rhBMP-2 in combination with or
      without ADSC is helpful to promote bone regeneration in high-speed distraction
      osteogenesi s of adult rabbit cranium.

PMID- 23952563
TI  - Biological phenotypes underpin the physio-somatic symptoms of somatization,
      depression, and chronic fatigue syndrome.
AB  - OBJECTIVE: Somatization is a symptom cluster characterized by 'psychosomatic'
      symptoms, that is, medically unexplained symptoms, and is a common component of
      other conditions, including depression and myalgic encephalomyelitis/chronic
      fatigue syndrome (ME/CFS). This article reviews the data regarding the
      pathophysiological foundations of 'psychosomatic' symptoms and the implications
      that this has for conceptualization of what may more appropriately be termed
      physio-somatic symptoms. METHOD: This narrative review used papers published in
      PubMed, Scopus, and Google Scholar electronic databases using the keywords:
      depression and chronic fatigue, depression and somatization, somatization and
      chronic fatigue syndrome, each combined with inflammation, inflammatory,
      tryptophan, and cell-mediated immune (CMI). RESULTS: The physio-somatic symptoms
      of depression, ME/CFS, and somatization are associated with specific biomarkers
      of inflammation and CMI activation, which are correlated with, and causally
      linked to, changes in the tryptophan catabolite (TRYCAT) pathway. Oxidative and
      nitrosative stress induces damage that increases neoepitopes and autoimmunity
      that contribute to the immuno-inflammatory processes. These pathways are all
      known to cause physio-somatic symptoms, including fatigue, malaise, autonomic
      symptoms, hyperalgesia, intestinal hypermotility, peripheral neuropathy, etc.
      CONCLUSION: Biological underpinnings, such as immune-inflammatory pathways, may
      explain, at least in part, the occurrence of physio-somatic symptoms in
      depression, somatization, or myalgic encephalomyelitis/chronic fatigue syndrome
      and thus the clinical overlap among these disorders.

PMID- 23952564
TI  - Diastereo- and enantioselective three-component coupling approach to highly
      substituted pyrrolidines.
AB  - The enantioselective synthesis of substituted pyrrolidines through a mild Lewis
      acid catalyzed three-component coupling reaction between picolinaldehyde, amino
      acids, and activated olefins is reported. The reaction uses low catalyst loadings
      of commercially available chiral diamines and copper triflate proposed to self
      assemble in conjunction with the chelating aldehydes, 4-substituted-2
      picolinaldehydes or 4-methylthiazole-2-carboxaldehyde, to generate a catalyst
      complex. A model is provided to explain how this complex directs
      enantioselectivity. This work represents a significant advance in the ease,
      scope, and cost of producing highly substituted, enantioenriched pyrrolidines. 

PMID- 23952565
TI  - Comparative efficacy of the picture exchange communication system (PECS) versus a
      speech-generating device: effects on social-communicative skills and speech
      development.
AB  - The Picture Exchange Communication System (PECS) and a speech-generating device
      (SGD) were compared in a study with a multiple baseline, alternating treatment
      design. The effectiveness of these methods in increasing social-communicative
      behavior and natural speech production were assessed with three elementary school
      aged children with severe autism who demonstrated extremely limited functional
      communication skills. Results for social-communicative behavior were mixed for
      all participants in both treatment conditions. Relatively little difference was
      observed between PECS and SGD conditions. Although findings were inconclusive,
      data patterns suggest that Phase II of the PECS training protocol is conducive to
      encouraging social-communicative behavior. Data for speech outcomes did not
      reveal any increases across participants, and no differences between treatment
      conditions were observed.

PMID- 23952566
TI  - Impacts of a PECS instructional coaching intervention on practitioners and
      children with autism.
AB  - There is a growing research literature on the potential benefits of augmentative
      and alternative communication (AAC) for individuals with autism; however few
      studies have investigated implementation of AAC within real-life contexts. Thus,
      the purpose of this study was to investigate the impact of training for
      practitioners in implementation of aided AAC, and to examine implementation of
      Picture Exchange Communication System (PECS) in real-life contexts. In
      particular, this study involved the implementation of instructional coaching to
      increase opportunities offered by behavioral therapists for their preschool-aged
      clients to use PECS to make requests. Results indicated increases in therapist
      implementation of AAC and client use of AAC in trained contexts, with limited
      generalization to untrained contexts.

PMID- 23952567
TI  - Confirming and denying in co-construction processes: a case study of an adult
      with cerebral palsy and two familiar partners.
AB  - For individuals with complex communication needs, one of the most frequent
      communicative strategies is the co-construction of meaning with familiar
      partners. This preliminary single-case study gives insight into a special
      sequential pattern of co-construction processes - the search sequence -
      particularly in relation to the processes of confirming and denying meanings
      proposed by familiar interaction partners. Five different conversations between
      an adult with cerebral palsy and complex communication needs and two familiar co
      participants were videotaped and analyzed using the methodology of conversation
      analysis (CA). The study revealed that confirmations and denials are not simply
      two alternative actions, but that several possibilities to realize confirmations
      and denials exist that differ in their frequency and that have different
      consequences for the sequential context. This study of confirmations and denials
      demonstrates that co-construction processes are more complex than have previously
      been documented.

PMID- 23952568
TI  - Reduction of infrasounds in machines with hydrostatic drive.
AB  - Some hazards posed by the operation of hydraulic systems, connected with low
      frequency vibrations and noise are presented. Special attention is focused on
      infrasounds. The sources of low-frequency vibrations and noise and ways of
      reducing them are indicated. An original solution ensuring the effective
      reduction of vibrations and noise in a wide frequency range, i.e., a wide-band
      damper of pressure fluctuations, also performing the function of an acoustic
      filter, is proposed. The effectiveness of the damper was confirmed by the results
      of laboratory tests and tests carried out on engineering machines working in real
      conditions. 

PMID- 23952569
TI  - CuCl2 for the isolation of a broad array of endohedral fullerenes containing
      metallic, metallic carbide, metallic nitride, and metallic oxide clusters, and
      separation of their structural isomers.
AB  - A typical arc-synthesis generates many types of fullerenes and endohedrals.
      Resulting soot extracts contain a complex mixture of >50 types of fullerenes,
      metallofullerenes, and their structural isomers. Prior to application
      development, novel separation methods are required to fractionate this rich array
      of metallic, metallic carbide, metallic nitride, and metallic oxide endohedrals,
      all of which can be present in a single, soot extract. Herein, we report the
      discovery of CuCl2 as a Lewis acid that will selectively precipitate only the
      more reactive members of each of these endohedral families. The more reactive
      Sc4O2@Ih-C80, Sc3C2@Ih-C80, and Sc3N@D3h-C78 endohedrals are quickly removed from
      extracts to greatly decrease the number of endohedrals present in a sample.
      Experiments indicate that enrichment factors of several orders of magnitude can
      be achieved within minutes of reaction time. CuCl2 also has sufficient
      selectivity to resolve and separate structural isomers, as demonstrated with
      Er2@C82 (isomer I, Cs(6)-C82 versus isomer III). The selective complexation of
      CuCl2 with fullerenes can be correlated to their first oxidation potential. We
      estimate a significantly lower threshold of precipitation for CuCl2 (<0.19 V)
      compared to stronger Lewis acids. Fullerenes and metallofullerenes having first
      oxidation potentials above 0.19 V tend to remain unreacted in solution. In
      contrast, species with first oxidation potentials below 0.19 V (vs Fc/Fc(+))
      precipitate via complexation, and are easily decomplexed. CuCl2 is compared to
      Lewis acids having higher precipitation thresholds (e.g., FeCl3) in our goal to
      predict a priori which endohedrals would remain in solution versus which
      endohedral species would complex and precipitate. The ability to predict
      endohedral precipitation a priori is beneficial to the design of purification
      strategies for metallofullerenes. 

PMID- 23952570
TI  - Yield stress and scaling of polyelectrolyte multilayer modified suspensions:
      effect of polyelectrolyte conformation during multilayer assembly.
AB  - The yield stress of polyelectrolyte multilayer modified suspensions exhibits a
      surprising dependence on the polyelectrolyte conformation of multilayer films.
      The rheological data scale onto a universal master curve for each polyelectrolyte
      conformation as the particle volume fraction, phi, and the ionic strength of the
      background fluid, I, are varied. It is shown that rough films with highly coiled,
      brushy polyelectrolytes significantly enhance the yield stress. Moreover, via the
      ionic strength I of the background fluid, the dynamic yield stress of brushy
      polyelectrolyte multilayers can be finely adjusted over 2 decades.

PMID- 23952571
TI  - Promoting the consumer voice in palliative care: exploring the possibility of
      using consumer impact statements.
AB  - BACKGROUND: It can be difficult to engage consumers in health decision making.
      This is particularly so in the area of palliative care, where consumers are very
      unwell and are unlikely to become involved in long-term programmes that promote
      consumer input. This paper explores the possibility of using 'Consumer Impact
      Statements' to facilitate the inclusion of the viewpoint of people at the end of
      life in the process of policy and decision making, particularly in the area of
      subsidy of pharmaceuticals used in palliative care. SEARCH STRATEGY: A broad
      search was conducted to find information about the use of impact statements in
      any health field. The health literature and grey literature were searched to
      explore the use of Consumer Impact Statements to date. RESULTS: No papers were
      found describing the use of Consumer Impact Statements in the palliative care
      setting. Health impact assessment is used in the areas of environmental health
      and community health. Impact statements are less commonly used in other areas of
      health, especially policy development, and no formal description of a Consumer
      Impact Statement was found. DISCUSSION: There is considerable scope for
      developing the use of Consumer Impact Statements to promote the consumer
      viewpoint in health decision making, because it will allow people who are
      otherwise unlikely to contribute to the public debate to have their views heard
      by decision makers. CONCLUSION: The use of Consumer Impact Statements is
      particularly suited to palliative care, given that consumers are often otherwise
      unable to contribute to the public debate.

PMID- 23952572
TI  - Identification of RAPD-SCAR marker linked to white spot syndrome virus resistance
      in populations of giant black tiger shrimp, Penaeus monodon Fabricius.
AB  - White spot disease (WSD) caused by white spot syndrome virus (WSSV) creates
      severe epizootics in shrimp aquaculture industry worldwide. Despite several
      efforts, no such permanent remedy was yet developed. Selective breeding using DNA
      markers would be a cost-effective strategy for long-term solution of this
      problem. In the present investigation, out of 30 random primers, only one primer
      produced a statistically significant (P < 0.01) randomly amplified polymorphic
      DNA (RAPD) marker of 502 bp, which provided a good discrimination between disease
      resistant and disease susceptible populations of Penaeus monodon from three
      geographical locations along the East coast of India. Because RAPD markers are
      dominant, a sequence characterized amplified region (SCAR) marker was developed
      by cloning and sequencing of 502 bp RAPD fragment, which generates a single 457
      bp DNA fragment after PCR amplification only in the disease resistant shrimps.
      Challenge experiment was also conducted to validate this 457 bp SCAR marker, and
      the results suggested that the WSSV loads were 2.25 * 10(3) fold higher in
      disease susceptible than that in disease resistant shrimps using real-time PCR.
      Therefore, this 457 bp DNA SCAR marker will be very valuable towards the
      development of disease-free shrimp aquaculture industry.

PMID- 23952573
TI  - The MnSOD Ala16Val SNP: relevance to human diseases and interaction with
      environmental factors.
AB  - The relevance of reactive oxygen species (ROS) production relies on the dual role
      shown by these molecules in aerobes. ROS are known to modulate several
      physiological phenomena, such as immune response and cell growth and
      differentiation; on the other hand, uncontrolled ROS production may cause
      important tissue and cell damage, such as deoxyribonucleic acid oxidation, lipid
      peroxidation, and protein carbonylation. The manganese superoxide dismutase
      (MnSOD) antioxidant enzyme affords the major defense against ROS within the
      mitochondria, which is considered the main ROS production locus in aerobes.
      Structural and/or functional single nucleotide polymorphisms (SNP) within the
      MnSOD encoding gene may be relevant for ROS detoxification. Specifically, the
      MnSOD Ala16Val SNP has been shown to alter the enzyme localization and
      mitochondrial transportation, affecting the redox status balance. Oxidative
      stress may contribute to the development of type 2 diabetes, cardiovascular
      diseases, various inflammatory conditions, or cancer. The Ala16Val MnSOD SNP has
      been associated with these and other chronic diseases; however, inconsistent
      findings between studies have made difficult drawing definitive conclusions.
      Environmental factors, such as dietary antioxidant intake and exercise have been
      shown to affect ROS metabolism through antioxidant enzyme regulation and may
      contribute to explain inconsistencies in the literature. Nevertheless, whether
      environmental factors may be associated to the Ala16Val genotypes in human
      diseases still needs to be clarified.

PMID- 23952574
TI  - Function of isoamylase-type starch debranching enzymes ISA1 and ISA2 in the Zea
      mays leaf.
AB  - Conserved isoamylase-type starch debranching enzymes (ISAs), including the
      catalytic ISA1 and noncatalytic ISA2, are major starch biosynthesis determinants.
      Arabidopsis thaliana leaves require ISA1 and ISA2 for physiological function,
      whereas endosperm starch is near normal with only ISA1. ISA functions were
      characterized in maize (Zea mays) leaves to determine whether species-specific
      distinctions in ISA1 primary structure, or metabolic differences in tissues, are
      responsible for the differing ISA2 requirement. Genetic methods provided lines
      lacking ISA1 or ISA2. Biochemical analyses characterized ISA activities in mutant
      tissues. Starch content, granule morphology, and amylopectin fine structure were
      determined. Three ISA activity forms were observed in leaves, two ISA1/ISA2
      heteromultimers and one ISA1 homomultimer. ISA1 homomultimer activity existed in
      mutants lacking ISA2. Mutants without ISA2 differed in leaf starch content,
      granule morphology, and amylopectin structure compared with nonmutants or lines
      lacking both ISA1 and ISA2. The data imply that both the ISA1 homomultimer and
      ISA1/ISA2 heteromultimer function in the maize leaf. The ISA1 homomultimer is
      present and functions in the maize leaf. Evolutionary divergence between monocots
      and dicots probably explains the ability of ISA1 to function as a homomultimer in
      maize leaves, in contrast to other species where the ISA1/ISA2 heteromultimer is
      the only active form. 

PMID- 23952575
TI  - Systemic effects of fractionated, whole-brain irradiation in young adult and
      aging rats.
AB  - Cranial irradiation is a critical and effective treatment for primary brain
      tumors and metastases. Unfortunately, most patients who are treated and survive
      for more than a few months develop neural and cognitive problems as the result of
      radiation-induced normal tissue injury. The neurobiological mechanisms underlying
      these cognitive deficits remain largely unknown and there are no validated
      treatments to prevent or ameliorate them; thus, there is a significant and
      continuing need for preclinical studies in animal models. Investigations from
      several laboratories have demonstrated neurobiological changes after cranial
      irradiation in rodents. To date, however, experimental studies in animal models
      have included little assessment of the systemic effects of cranial irradiation,
      despite evidence from the clinic that cranial irradiation results in changes
      throughout the body and recognition that systemic responses may influence the
      development of neural and cognitive deficits. This study evaluated systemic
      effects of clinically relevant, fractionated whole-brain irradiation in adult
      rats and demonstrates effects on the growth hormone/insulin-like growth factor-I
      axis, which may contribute to the development of neural changes. These and other
      systemic responses are important to consider in ongoing efforts to understand the
      mechanisms of radiation-induced normal tissue injury. 

PMID- 23952576
TI  - Genistein nanoparticles protect mouse hematopoietic system and prevent
      proinflammatory factors after gamma irradiation.
AB  - Previous studies demonstrated that genistein protects mice from radiation-induced
      bone marrow failure. To overcome genistein's extremely low water solubility, a
      nanoparticle suspension of genistein has been formulated for more rapid
      dissolution. In the current study, we evaluated the radioprotective effects of a
      nanoparticle formulation of genistein on survival and hematopoietic recovery in
      mice exposed to total-body gamma irradiation. A single intramuscular injection of
      a saline-based genistein nanosuspension (150 mg/kg) administered to CD2F1 mice 24
      h before 9.25 Gy (60)Co radiation exposure resulted in a 30-day survival rate of
      95% compared to 25% in vehicle-treated animals. In mice irradiated at 7 Gy, the
      genistein nanosuspension increased mouse bone marrow cellularity from
      approximately 2.9% (vehicle treated) to 28.3% on day 7 postirradiation. Flow
      cytometry analysis demonstrated decreased radiation-induced hematopoietic stem
      and progenitor cell (HSPC, Lineage(-)/cKit(+)) death from 77.0% (vehicle) to
      43.9% (genistein nanosuspension) with a significant recovery of clonogenicity 7
      days after irradiation. The genistein nanosuspension also attenuated the
      radiation-induced elevation of proinflammatory factors interleukin 1 beta (IL
      1beta), IL-6 and cyclooxygenase-2 (COX-2) in mouse bone marrow and spleen, which
      may contribute to protecting HSPCs. 

PMID- 23952577
TI  - Spatiotemporal characteristics of internal radiation exposure in evacuees and
      first responders after the radiological accident in fukushima.
AB  - After the Tokyo Electric Power Company Fukushima Daiichi nuclear power plant
      accident on March 11, 2011, the reconstruction of early internal radiation doses
      in residents of Fukushima plays a major role in evaluating their future heath
      risk, including thyroid cancer by internal radioiodine. Internal radioactivity
      was measured using a whole body counter (WBC) at the Nagasaki University Medical
      School to evaluate the health risks of residents and short term visitors in
      Fukushima. Measurable (131)I, (134)Cs and (137)Cs were detected altogether in 49
      out of 196 people who were in Fukushima prefecture at any time during March 11
      and April 20, 2011. In 49 people, the 90 percentile of the thyroid equivalent
      dose by (131)I and the committed effective dose (total effective dose over a
      lifetime) by the sum of (134)Cs and (137)Cs was 3 mSv and 0.06 mSv, respectively.
      The radionuclide intakes in early evacuees who left Fukushima before March 16
      were more than five times as high as in the responders who moved to Fukushima
      later. The intake ratio of (131)I/(137)Cs of the earlier evacuees was
      approximately three. The spatial analysis of 16 evacuees to the south indicated a
      reduction of internal radioactivity depending on the distance from the nuclear
      power plant. Among them, high internal (131)I radioactivity in 6 people in a
      particular evacuation route could be explained by the arrival of a radioactive
      cloud with a high airborne (131)I/(137)Cs ratio to the environment, as predicted
      by atmospheric dispersion simulations. Overall, the actual internal radioactivity
      assessed by a WBC examination comparatively agreed with the predicted airborne
      radioactivity. These results suggest that the accurate estimation of internal
      doses in the first week after the radiological accident is critical for the dose
      reconstruction. The evaluation of internal doses of residents based on their
      evacuation routes and the advanced estimation of airborne radioactivity from the
      atmospheric dispersion model should continue to be assessed. 

PMID- 23952578
TI  - Successful treatment of acute myeloid leukaemia in a patient with ataxia
      telangiectasia.
AB  - Ataxia telangiectasia (AT) is a rare autosomal recessive multisystem disorder
      characterised by cerebellar degeneration, immunodeficiency and cancer
      predisposition. Around 10% of AT patients develop lymphoid malignancies, but the
      development of myeloid leukaemia with AT (AT-AML) is extremely rare, and there
      have been no previous publications regarding suitable therapies. Here, we first
      describe a successful therapeutic experience in a patient with AT-AML (FAB-M1)
      who attained remission after induction therapy and maintained stable disease for
      a year. To minimise therapy-induced toxicity, low-dose induction was applied
      first, though this was obviously insufficient and the patient subsequently
      responded well to dose-intensified short-term chemotherapy. In this report, we
      suggest a curative therapeutic approach for AT-AML, though the issue of how best
      to manage patients with cancer complicated by immunodeficiency remains undecided.

PMID- 23952579
TI  - Cardiac cell culture model as a left ventricle mimic for cardiac tissue
      generation.
AB  - A major challenge in cardiac tissue engineering is the delivery of hemodynamic
      mechanical cues that play a critical role in the early development and maturation
      of cardiomyocytes. Generation of functional cardiac tissue capable of replacing
      or augmenting cardiac function therefore requires physiologically relevant
      environments that can deliver complex mechanical cues for cardiomyocyte
      functional maturation. The goal of this work is the development and validation of
      a cardiac cell culture model (CCCM) microenvironment that accurately mimics
      pressure-volume changes seen in the left ventricle and to use this system to
      achieve cardiac cell maturation under conditions where mechanical loads such as
      pressure and stretch are gradually increased from the unloaded state to
      conditions seen in vivo. The CCCM platform, consisting of a cell culture chamber
      integrated within a flow loop was created to accomplish culture of 10 day chick
      embryonic ventricular cardiomyocytes subject to 4 days of stimulation (10 mmHg,
      ~13% stretch at a frequency of 2 Hz). Results clearly show that CCCM conditioned
      cardiomyocytes accelerate cardiomyocyte structural and functional maturation in
      comparison to static unloaded controls as evidenced by increased proliferation,
      alignment of actin cytoskeleton, bundle-like sarcomeric alpha-actinin expression,
      higher pacing beat rate at lower threshold voltages, and increased shortening.
      These results confirm the CCCM microenvironment can accelerate immature cardiac
      cell structural and functional maturation for potential cardiac regenerative
      applications. 

PMID- 23952580
TI  - Closure of the uterine incision with one or two layers after caesarean section: a
      randomized controlled study in sheep.
AB  - OBJECTIVE: To compare the quality of the uterine scar with one or two layer
      closure after caesarean section by studying biomechanical and pathological
      properties of the scar. METHODS: A randomized controlled trial performed on eight
      term pregnant ewes assigned into two groups during caesarean according to type of
      uterine closure: single-layer or double-layer. Hysterectomy was performed 8
      months after caesarean delivery. Tensile strength of all scars and of unscarred
      myometrium was measured. Pathological properties of the scars were analyzed
      histologically. RESULTS: The force required to reach the yield point was similar
      between scarred and unscarred myometrium (p=0.96), and between the scars in
      single-layer and double-layer closure groups (p=0.65). There was a significant
      increase in fibrosis width on the superficial part of the uterus in the double
      layer closure group compared to the single-layer group (p=0.02). CONCLUSIONS:
      Double-layer uterine closure modified wound healing without significant change in
      biomechanical properties.

PMID- 23952581
TI  - Structural studies of hydroxylamine oxidoreductase reveal a unique heme cofactor
      and a previously unidentified interaction partner.
AB  - Hydroxylamine oxidoreductase (HAO) is a 24-heme homotrimeric enzyme that
      catalyzes the conversion of hydroxylamine to nitrite in nitrifying bacteria: a
      key reaction in the nitrogen cycle. One heme in each HAO monomer is a highly
      unusual heme P460 that is the site of catalysis. This was proposed to be a c-type
      heme that contained an additional porphyrin-tyrosine cross-link. Here, we report
      the crystal structure of HAO from Nitrosomonas europaea to 2.1 A resolution that
      defines a different model compatible with the crystallographic and biochemical
      data. The structure reveals that heme P460 contains two covalent cross-links
      between the porphyrin and a Tyr residue. In addition, the enzyme was purified
      from source, and an unknown physiological HAO binding partner was present within
      the crystal (annotated in the genome as hypothetical protein NE1300). NE1300 may
      play a structural role in the ternary complex with cytochrome c554, the
      physiological electron acceptor of HAO. 

PMID- 23952582
TI  - Cr(VI) Formation related to Cr(III)-muscovite and birnessite interactions in
      ultramafic environments.
AB  - Chromium is abundantly and primarily present as Cr(III) in ultramafic rocks and
      serpentine soils. Chromium(III) oxidation involving chromite (FeCr2O4) via
      interactions with birnessite has been shown to be a major pathway of Cr(VI)
      production in serpentine soils. Alternatively, Cr(III)-bearing silicates with
      less Cr(III) may provide higher Cr(VI) production rates compared to relatively
      insoluble chromite. Of the potential Cr(III)-bearing silicates, Cr(III)-muscovite
      (i.e., fuchsite) commonly occurs in metamorphosed ultramafic rocks and
      dissolution rates may be comparable to other common Cr(III)-bearing
      phyllosilicates and clays. Here, we examine the formation of Cr(VI) related to
      Cr(III)-muscovite and birnessite (i.e., acid birnessite) interactions with and
      without humic matter (HM) via batch experiments. Experimentally, the fastest rate
      of Cr(VI) production involving Cr(III)-muscovite was 3.8 * 10(-1) MUM h(-1) (pH 3
      without HM). Kinetically, Cr(III)-muscovite provides a major pathway for Cr(VI)
      formation and Cr(VI) production rates may exceed those involving chromite
      depending on pH, available mineral surface areas in solution, and the abundance
      of Cr(III) present. However, when HM is introduced to the system, Cr(VI)
      production rates decrease by as much as 80%. This highlights that HM strongly
      decreases but may not completely suppress the formation and mobilization of
      Cr(VI). A Sri Lankan serpentine soil was utilized to provide context with regards
      to the experimental results. Despite Cr(VI) in the soil solids and Cr(VI)
      formation being favorable from Cr(III)-bearing minerals, no detectable Cr(VI) was
      released into soil solutions potentially due to the abundance of HM. Overall, the
      dynamic interactions of Cr(III)-bearing silicates and birnessite provide a
      kinetically favorable route of Cr(VI) formation which is tempered by humic
      matter. 

PMID- 23952583
TI  - Prevalence and associated factors of emotional and behavioural problems in
      Chinese school adolescents: a cross-sectional survey.
AB  - BACKGROUND: Emotional and behavioural problems are key health issues in
      adolescence. The aim of this study was to evaluate the prevalence of emotional
      and behavioural problems in Chinese school adolescents and to explore associated
      factors. METHODS: This cross-sectional study was conducted during the period of
      November/December 2009. A questionnaire including the Strengths and Difficulties
      Questionnaire (SDQ) self-reported version, and the characteristics of child (age,
      gender, only child and study pressure), parents (parent-adolescent relationship
      and parental expectations) and families (living area, family structure, socio
      economic status and negative life events) was distributed to our study
      population. A total of 5220 Chinese adolescents (aged 11-18) from 30 public
      schools in Liaoning province completed the questionnaire. Multivariate logistic
      analysis was used to explore the factors associated with emotional and
      behavioural problems. RESULTS: The average problem score was 11.28 (SD = 5.86)
      and the 10.7% scored above the cut-off for emotional and behavioural problems.
      Factors that increased the risk of having emotional and behavioural problems
      were: poor parent-adolescent relationship, experiencing more negative life
      events, older age, having study pressure, living in rural areas, boys and lower
      parental expectations. CONCLUSIONS: The prevalence of emotional and behavioural
      problems among Chinese adolescents was lower level compared with those reported
      in other countries. We found parent-adolescent relationship, negative life events
      and age to be the strongest contributing factors of emotional and behavioural
      problems.

PMID- 23952584
TI  - Effects of cardiac resynchronization therapy on muscle sympathetic nerve
      activity.
AB  - INTRODUCTION: Muscle sympathetic nerve activity (MSNA) is an independent
      prognostic marker in patients with heart failure (HF). Therefore, its relevance
      to the treatment of HF patients is unquestionable. OBJECTIVES: In this study, we
      investigated the effects of cardiac resynchronization therapy (CRT) on MSNA
      response at rest and during exercise in patients with advanced HF. METHODS: We
      assessed 11 HF patients (51 +/- 3.4 years; New York Heart Association class III
      IV; left ventricular ejection fraction 27.8 +/- 2.2%; optimal medical therapy)
      submitted to CRT. Evaluations were made prior to and 3 months after CRT. MSNA was
      performed at rest and during moderate static exercise (handgrip). Peak oxygen
      consumption (VO2 ) was evaluated by means of cardiopulmonary exercise test. HF
      patients with advanced NYHA class without CRT and healthy individuals were also
      studied. RESULTS: CRT reduced MSNA at rest (48.9 +/- 11.1 bursts/min vs 33.7 +/-
      15.3 bursts/min, P < 0.05) and during handgrip exercise (MSNA 62.3 +/- 13.1
      bursts/min vs 46.9 +/- 14.3 bursts/min, P < 0.05). Among HF patients submitted to
      CRT, the peak VO2 increased (12.9 +/- 2.8 mL/kg/min vs 16.5 +/- 3.9 mL/kg/min, P
      < 0.05) and an inverse correlation between peak VO2 and resting MSNA (r = -0.74,
      P = 0.01) was observed. CONCLUSIONS: In patients with advanced HF and severe
      systolic dysfunction: (1) a significant reduction of MSNA (at rest and during
      handgrip) occurred after CRT, and this behavior was significantly superior to HF
      patients receiving only medical therapy; (2) MSNA reduction after CRT had an
      inverse correlation with O2 consumption outcomes.

PMID- 23952585
TI  - Individual determinants of task division in older adults' mixed care networks.
AB  - Older adults in need of long-term care often receive help from both informal and
      formal caregivers. The division of tasks between these different types of
      caregivers may vary among such mixed care networks. Traditional models of task
      division suggest that formal and informal caregivers may either supplement each
      other or specialise in the care activities performed. Our study explores the
      determinants of various forms of task division in the Netherlands, using data
      collected in 2007 on 458 mixed care situations. Four types of task divisions of
      informal and formal care are distinguished: the complementation model [neither
      Activities of Daily Living (ADL) nor instrumental ADL (IADL) tasks shared, 14%],
      the supplementation model (both ADL and IADL tasks shared, 39%) and informal and
      formal specialisation (one type of task shared, one type of task not shared, 27%
      and 20% respectively). Marginal effects calculated with multinomial regression
      analyses show that the intensity of care provision, the informal caregivers'
      motives and the presence of privately paid help - more than care receiver's
      health - are related to type of task division with formal care. For example, when
      the informal caregiver provides more hours of help and out of a strong personal
      bond, the likelihood of informal specialisation increases, whereas the likelihood
      of formal specialisation decreases. When privately paid help is present, the
      complementation model is more likely, whereas the supplementation model is less
      likely to be found. Results are discussed regarding the differential consequences
      for co-ordination and co-operation in mixed care networks. 

PMID- 23952586
TI  - A database for Mycobacterium secretome analysis: 'MycoSec' to accelerate global
      health research.
AB  - Abstract Members of the genus Mycobacterium are notorious for their pathogenesis.
      Investigations from various perspectives have identified the pathogenic
      strategies employed by these lethal pathogens. Secretomes are believed to play
      crucial roles in host cell recognition and cross-talks, in cellular attachment,
      and in triggering other functions related to host pathogen interactions. However,
      a proper idea of the mycobacterial secretomes and their mechanism of
      functionality still remains elusive. In the present study, we have developed a
      comprehensive database of potential mycobacterial secretomes (MycoSec) using pre
      existing algorithms for secretome prediction for researchers interested in this
      particular field. The database provides a platform for retrieval and analysis of
      identified secretomes in all finished genomes of the family Mycobacteriaceae. The
      database contains valuable information regarding secretory signal peptides (Sec
      type), lipoprotein signal peptides (Lipo type), and Twin arginine (RR/KR) signal
      peptides (TAT type), prevalent in mycobacteria. Information pertaining to COG
      analysis, codon usage, and gene expression of the predicted secretomes has also
      been incorporated in the database. MycoSec promises to be a useful repertoire
      providing a plethora of information regarding mycobacterial secretomes and may
      well be a platform to speed global health research. MycoSec is freely accessible
      at http://www.bicnbu.in/mycosec . 

PMID- 23952588
TI  - Risk factors and predictors of levodopa-induced dyskinesia among multiethnic
      Malaysians with Parkinson's disease.
AB  - Chronic pulsatile levodopa therapy for Parkinson's disease (PD) leads to the
      development of motor fluctuations and dyskinesia. We studied the prevalence and
      predictors of levodopa-induced dyskinesia among multiethnic Malaysian patients
      with PD. METHODS: This is a cross-sectional study involving 95 patients with PD
      on uninterrupted levodopa therapy for at least 6 months. The instrument used was
      the UPDRS questionnaires. The predictors of dyskinesia were determined using
      multivariate logistic regression analysis. RESULTS: The mean age was 65.6 +/- 8.5
      years. The mean onset age was 58.5 +/- 9.8 years. The median disease duration was
      6 (7) years. Dyskinesia was present in 44% (n = 42) with median levodopa therapy
      of 3 years. There were 64.3% Chinese, 31% Malays, and 3.7% Indians and other
      ethnic groups. Eighty-one percent of patients with dyskinesia had clinical
      fluctuations. Patients with dyskinesia had lower onset age ( p < 0.001), longer
      duration of levodopa therapy ( p < 0.001), longer disease duration ( p < 0.001),
      higher total daily levodopa dose ( p < 0.001), and higher total UPDRS scores ( p
      = 0.005) than patients without dyskinesia. The three significant predictors of
      dyskinesia were duration of levodopa therapy, onset age, and total daily levodopa
      dose. CONCLUSIONS: The prevalence of levodopa-induced dyskinesia in our patients
      was 44%. The most significant predictors were duration of levodopa therapy, total
      daily levodopa dose, and onset age.

PMID- 23952590
TI  - Memory characteristics of kinesthetic information.
AB  - Several kinesthetic cues may underlie the retention of movements: joint position
      receptors, muscle stretch receptors, tendon stretch receptors, cutaneous senses,
      duration of movements, and motor outflow all provide cues. An attempt was made to
      separate subsets of cues used for movement reproduction by varying the
      characteristics of the movements. Ss reproduced either the end Location of a
      movement or the Distance plus Location. The original and reproduction movements
      involved either the same or different muscle tensions. These manipulations failed
      to result in different retention characteristics. In all cases there was little
      loss of accuracy over a 7-sec. retention interval unless the retention interval
      was filled with a distracting task. These results are quite different from those
      of a number of other studies of movement retention, suggesting that different
      cues do have different retention characteristics. 

PMID- 23952589
TI  - Quantitative analysis of fecal flora in goat kids with and without floppy kid
      syndrome.
AB  - BACKGROUND: Floppy kid syndrome (FKS) affects goat kids in the first month of
      life and is associated with high morbidity and mortality rates. The condition is
      characterized by neurological signs that can be ascribed to increased plasma D
      lactate concentrations. The source of D-lactate has not been identified
      conclusively, but D-lactate-producing bacteria in the large intestine are thought
      to be involved. OBJECTIVES: To determine the number of colony-forming unit (CFUs)
      of certain groups of bacteria in the feces of kids with and without FKS. ANIMALS:
      Nineteen goat kids with clinical signs of FKS, acidemia (pH <= 7.2), and plasma D
      lactate concentration >7 mM and 15 healthy goat kids without acidemia (pH >7.2)
      and D-lactate concentration <1 mM. METHODS: In this case-control study, the goat
      kids were examined clinically and blood was collected to measure D-lactate
      concentration, blood gases, and acid-base parameters. Fecal samples were
      collected and the total aerobic bacterial count and CFU counts of coliforms,
      enterococci, staphylococci, streptococci, lactobacilli, and clostridia were
      determined using the surface plating method. RESULTS: Goat kids with FKS had a
      mean plasma D-lactate concentration of 10.9 +/- 3.7 mM compared with 0.3 +/- 0.9
      mM in healthy kids, and significantly greater CFU counts for enterococci,
      streptococci, staphylococci, and lactobacilli than healthy kids. CONCLUSIONS AND
      CLINICAL IMPORTANCE: The groups of bacteria present in greater numbers in the
      feces of goat kids with FKS include several D-lactate-producing species, which
      makes dysbacteriosis a likely cause of the increased plasma D-lactate
      concentration in FKS.

PMID- 23952591
TI  - Psychophysics of kinesthesis.
AB  - A horizontal straight-arm movement was used to determine the relationship between
      the physical stimulus continuum and the psychological continuum of kinesthetic
      extent of arm movement. A power function with an exponent of 1.075 best described
      this relationship. In addition, to classify extent of movement as belonging to
      either a prothetic or metathetic continuum, the category scale was derived.
      According to the functional criteria described by Stevens (1957), extent of
      movement was subserved by a metathetic process which would indicate that, for the
      present task, judgments were made through the use of positional cues rather than
      amplitude cues. 

PMID- 23952592
TI  - Evidence for an error detection mechanism in motor skills.
AB  - One of the fundamental predictions of the Adams (1971) closed-loop theory is that
      S should develop over practice a perceptual trace which forms the basis of an
      error detection mechanism. If knowledge of results (KR) is withdrawn, S can use
      the error detection mechanism to guide performance in its place. To test this
      notion, 10 Ss practiced 170 trials of a discrete ballistic response, attempting
      to produce a 9.5-in. manual slider movement in exactly 150 msec., with KR present
      except on Trials 11-20 and 141-170. There was an increasing correspondence
      between the actual errors and Ss' estimation of them as practice continued, and
      ratings of confidence increased, both of which were indicative of a developing
      error detection mechanism. During KR withdrawal trials, Ss displayed no worsening
      of performance, and even continued to learn slightly, suggesting that the error
      detection mechanism acted as a substitute for KR. The results generally supported
      Adams' theory. 

PMID- 23952593
TI  - The development of a simple ballistic skill with and without visual control.
AB  - 80 randomly selected male Ss discriminated the "effort" required to perform a
      simple 1-handed ballistic aiming task: aligning a Fletcher's Trolley with a
      pointer placed at varying distances adjacent to an inclined wooden track. Groups
      were aged 5-6, 10-11, 15-16, and 18 or more yr., with 10 Ss able to see both
      hands and target while the other 10 could see neither. A split-plot factorial
      design was used. On excluding the 5-6 yr.-old "Nonvision" children, the remaining
      7 sub-groups were shown to be homogeneous. Mean absolute error scores increased
      with Distance, and also with a decrease in Age. In the "Non-vision" condition
      accuracy was reduced still further for all Ss. Age, Vision, and Distance and the
      interaction of Age with Vision were all significant, p<.01. 

PMID- 23952594
TI  - The effect of exercise on the visual and auditory acuity of table-tennis players.
AB  - Utilizing a simulated table-tennis task, improved visual and auditory acuity of a
      group of 13 Ss was found after a playing period of 10 min. 2 passive control
      groups, 1 observing ball flight and the other a static display, showed no
      significant improvements in either visual or auditory acuity. The results are
      interpreted in terms of sensory facilitation brought about by increased arousal
      resulting from gross-bodily activity. 

PMID- 23952595
TI  - Direction and extent uncertainty in step-input tracking.
AB  - In 3 experiments, Ss controlled a horizontal lever to track a step input where
      the degrees of choice of direction and extent of movement were varied
      systematically. The experiments differed in the way the trials were presented and
      in the conditions under which these 2 sources of response choice were compared.
      Increasing choice of direction of movement from 1 to 2 led to an increase in RT
      of between 34 and 40 msec. No significant increase in RT was found as choice of
      extent of movement was raised from 1 to 4. Considered with other evidence the
      results indicate the necessity to distinguish 2 types or levels of decisions
      associated with response factors. It is suggested that at one level the
      sequencing of muscle activity is established and at another the fine details of
      this activity are controlled. 

PMID- 23952596
TI  - Retention of fast and slow learners following overlearning of a gross motor
      skill.
AB  - 45 university Ss practiced balancing on a stabilometer to a performance criterion
      (Day 1) and then were designated as fast, medium, and slow learners based on the
      number of trials needed to attain it. Each S received an additional number of
      trials the following day (Day 2) equal to the number needed to reach the
      criterion (100% overlearning). Absolute and relative retention scores were
      calculated following a retention interval of 1 wk. No significant difference was
      found between the fast and slow learners on absolute recall, although the results
      favored the fast learners. The fast learners showed significant reminiscence
      between Day 1 and Day 2 and following the 1-wk. retention interval. It was
      concluded that the "equal amount learned" method did not discriminate against the
      fast learner and that speed of learning may be an important factor in determining
      whether or not reminiscence occurs following the attainment of a performance
      criterion. 

PMID- 23952587
TI  - Patients with Type 1 diabetes consuming alcoholic spirits have an increased risk
      of microvascular complications.
AB  - AIMS: Our aim was to evaluate the effect of the amount of alcohol consumption and
      the type of beverage on the risk of diabetic nephropathy and severe diabetic
      retinopathy. METHODS: The alcohol consumption data were available from 3608
      patients with Type 1 diabetes participating in the Finnish Diabetic Nephropathy
      Study (FinnDiane). We assessed the cross-sectional association between alcohol
      consumption and diabetic nephropathy as well as retinopathy. Patients were
      divided into different groups according to the amount of alcohol and the type of
      beverage they were consuming. RESULTS: In the multivariate analysis, the odds
      ratio for nephropathy was 1.39 (95% CI 1.05-1.84) for abstainers and 2.44 (95% CI
      1.49-3.99) for former users compared with light consumers. The results were
      similar in retinopathy, with an odds ratio of 1.42 (95% CI 1.11-1.82) for
      abstainers and 1.73 (95% CI 1.07-2.79) for former users. No difference between
      light consumers and moderate or heavy consumers was observed. Compared with wine
      drinkers, men consuming mostly alcoholic spirits had a higher risk of nephropathy
      with an odds ratio of 2.80 (95% CI 1.15-6.81). In women, there was no difference
      in the risk of nephropathy between the different beverage types. Alcoholic spirit
      consumers had a higher risk of retinopathy with an odds ratio of 2.32 (95% CI
      1.35-4.00). There was no difference between wine and beer consumers. CONCLUSIONS:
      Alcoholic spirit drinkers carry a higher risk of nephropathy and severe
      retinopathy compared with wine drinkers. Lifelong abstainers and former users of
      alcohol have a higher risk of nephropathy and severe retinopathy compared with
      light consumers.

PMID- 23952597
TI  - Pursuit tracking skill with separate and combined visual and auditory feedback.
AB  - This investigation was concerned with the learning of a pursuit tracking skill
      under 3 experimental conditions, all with a narrow circular track for stylus
      guidance: visual feedback (V), auditory feedback (A), and visual plus auditory
      feedback (V+A). A Control Condition V was run on the standard USAF Rotary Pursuit
      turntable (n = 100 Ss). Groups of 4 Ss were given preliminary training under
      Condition V for a block of 5 30-sec. trials (20 sec. work, 10 sec. rest). All Ss
      then received 25 trials each under the 3 conditions, a total of 80 trials., (n =
      84 Ss). In Exp. 1 36 Ss were run in 3 counterbalanced condition orders; in Exp. 2
      48 Ss were run in all 6 permutations. RESULTS: (1) visual feedback was
      significantly superior to auditory feedback, (2) response guidance (narrow track)
      was highly effective as compared with the standard (no-track) turntable, (3) men
      were significantly more proficient than women in Conditions V and V+A, (4)
      Condition V+A was only slightly superior to Condition V, (5) auditory feedback
      while tracking blind was not relevant to the acquisition of pursuit skill under
      these conditions, (6) all differences were attributed to performance rather than
      to learning variables.

PMID- 23952599
TI  - Response to 'A systematic review and meta-regression analysis of aggression
      during first episode of psychosis'. Reply.

PMID- 23952598
TI  - Synthesis of nitrogenated heterocycles by asymmetric transfer hydrogenation of N
      (tert-butylsulfinyl)haloimines.
AB  - Highly optically enriched, protected, nitrogenated heterocycles with different
      ring sizes have been synthesized by a very efficient methodology consisting of
      the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)haloimines
      followed by treatment with a base to promote an intramolecular nucleophilic
      substitution process. N-protected aziridines, pyrrolidines, piperidines, and
      azepanes bearing aromatic, heteroaromatic, and aliphatic substituents have been
      obtained in very high yields and diastereomeric ratios up to >99:1. The free
      heterocycles can be easily obtained by a simple and mild desulfinylation
      procedure. Both enantiomers of the free heterocycles can be prepared with the
      same good results by changing the absolute configuration of the sulfur atom of
      the sulfinyl group.

PMID- 23952600
TI  - The relationship between tirasemtiv serum concentration and functional outcomes
      in patients with ALS.
AB  - Tirasemtiv is a fast skeletal muscle activator that increases efficiency of
      muscle contraction. Both single and repeated dose studies suggested beneficial
      effects on measures of function, muscle strength and endurance. As the outcomes
      measured were identical in previous studies and the duration of all studies was
      21 days or less, we pooled data from all studies and assessed the relationship
      between outcomes and plasma tirasemtiv concentration to assess consistency of
      observations as well as to increase sensitivity. We pooled data for ALSFRS-R,
      three pulmonary function measures, quantitative muscle strength, and submaximal
      handgrip endurance. Up to 855 values from 143 patients were plotted against
      tirasemtiv concentrations. Linear associations between tirasemtiv concentrations
      and changes from baseline of clinical measures were estimated using a repeated
      measures mixed model. Trends toward improvement were noted in all measures except
      for vital capacity, despite the fact that time was not included as a factor so
      that any time-related decline acted to reduce the magnitude of any noted trend.
      In conclusion, tirasemtiv appears to have concentration-dependent beneficial
      effects on both function and measures of strength and endurance when administered
      for up to 21 days, even when time is eliminated as a cofactor. These findings
      further support the development of this agent in ALS.

PMID- 23952601
TI  - Non-thermal plasmas induced electrostatic stress on corneocyte desquamation.
AB  - The advent of non-thermal plasma brought a breakthrough in exploring its clinical
      applications in dermatology to bolster tissue generation in the domain of plasma
      medicine. This study aimed to investigate the effect of non-thermal plasma on the
      corneocyte of the skin cells, in treating superficial skin diseases via the
      process of corneocyte desquamation, a probable mechanism for skin cell
      proliferation. The postulated brick and mortar arrangement of corneocytes in the
      stratum corneum was modeled consisting of three corneocytes and three
      corneodesmosomes in a simulation domain of 40.30 * 3.00 MUm2 using Maxwell 2D
      finite element analyzer. The corneocyte desquamation was quantified by the
      weakening of corneodesmosomes due to electrostatic pressure (~530 MV/m) on the
      corneodesmosome surface exceeding its tensile strength (~76 MPa). A mathematical
      model displaying a relationship between the plasma potential and the skin tensile
      strength is also presented in this investigation. The non-thermal plasma could
      emerge as a clean and dry therapy to treat superficial skin diseases. Our study
      propels investigating the interaction of non-thermal plasma with the wet tissue
      in the deeper layer (dermis) of the skin cells and also, the development of such
      instruments for a comprehensive skin treatment.

PMID- 23952602
TI  - Driving the interactions between organic nanoparticles and phospolipidic
      membranes by an easy treatment of the surface stabilizer.
AB  - Polymer-stabilized perylene nanoparticles were prepared through a solvent
      exchange method. The formation of the nanostructures in aqueous solution was
      confirmed by the appearance of a red-shifted emission attributable to the
      formation of excimer-like aggregates. The behavior of organic nanostructures in
      the presence of lipid vesicles was investigated through steady-state and time
      resolved fluorescence measurements. When no further surface treatment is applied
      to the nanoparticles, changes in the decay times and emission spectra demonstrate
      that inside the lipid bilayers the nanoparticles redissolve into the monomeric
      form with a rate and efficiency determined by the working temperature (above and
      below the transition temperature Tm of the phospholipid). On the other hand, when
      the stabilized shell is UV-cured to induce photo-cross-linking of the polymeric
      chains, the nanoparticle stability increases and their redissolution in the
      membrane is prevented. Confocal fluorescence images support the data obtained in
      bulk. The results indicate that the prepared nanostructures could be successfully
      used either as nanometric carriers for the delivery of poor water-soluble
      lipophilic compounds or as imaging tools depending on the rigidity/cross-linking
      degree of their polymeric stabilizer shell. 

PMID- 23952604
TI  - Polymer micelle assisted transport and delivery of model hydrophilic components
      inside a biological lipid vesicle: a coarse-grain simulation study.
AB  - Understanding drug transportation and delivery mechanism from a molecular
      viewpoint is essential to find better treatment pathways. Despite the fact that
      many significant drugs such as anticancer doxorubicin and mitoxantrone are
      predominantly hydrophilic, an efficient methodology to deliver hydrophilic drug
      components is not well established. Here we explore this problem by studying
      "patchy" polymeric micelle assisted hydrophilic component transportation across a
      lipid membrane and delivery inside a biological lipid vesicle. Using the MARTINI
      force field as the basis, we study the interaction of polymeric micelle with DPPC
      lipid vesicles in detail. In order to facilitate hydrophilic drug transportation
      study, a primitive CG model for hydrophilic drug component is used. Extensive
      simulations carried out over hundreds of nanoseconds demonstrate successful
      encapsulation, transportation of hydrophilic components by patchy polymeric
      micelles. Results show the polymeric micelle releases a significant portion of
      hydrophilic contents inside the lipid vesicle. The present simulation study also
      reveals a possible mechanism for efficient hydrophilic component transportation
      and delivery. Insights from this study could potentially help the experimental
      community to design better delivery vehicles, especially for hydrophilic drug
      molecules. 

PMID- 23952603
TI  - Patients' and clinicians' experiences and perceptions of the primary care
      management of insomnia: qualitative study.
AB  - BACKGROUND: Insomnia is common leading to patients with sleep problems often
      presenting to primary care services including general practice, community
      pharmacies and community mental health teams. Little is known about how health
      professionals in primary care respond to patients with insomnia. AIM: We aimed to
      explore health professionals' and patients' experiences and perceptions of the
      management of insomnia in primary care. DESIGN: We used a qualitative design and
      thematic approach. SETTING: Primary care in Nottinghamshire and Lincolnshire.
      METHOD: We undertook focus groups and one-to-one interviews with a purposive
      sample of health professionals and adults with insomnia. RESULTS: We interviewed
      28 patients and 23 health professionals. Practitioners focused on treating the
      cause of insomnia rather than the insomnia itself. They described providing
      stepped care for insomnia, but this focused on sleep hygiene which patients often
      disregarded, rather than cognitive behavioural therapy for insomnia (CBT-I).
      Practitioners were ambivalent towards hypnotic drugs but often colluded with
      patients to prescribe to avoid confrontation or express empathy. Patients
      sometimes took hypnotics in ways that were not intended, for example together
      with over-the-counter medication. Practitioners and patients were sometimes but
      not always concerned about addiction. Practitioners sometimes prescribed despite
      these concerns but at other times withdrew hypnotics abruptly without treating
      insomnia. Both patients and practitioners wanted more options and better training
      for the management of insomnia in primary care. CONCLUSION: A better
      understanding of the current approaches and difficulties in the management of
      insomnia will help to inform more therapeutic options and health professional
      training.

PMID- 23952605
TI  - Efficacy of garlic (Allium sativum) extract applied as a therapeutic immersion
      treatment for Neobenedenia sp. management in aquaculture.
AB  - Garlic, Allium sativum L., extract administered as a therapeutic bath was shown
      to have antiparasitic properties towards Neobenedenia sp. (MacCallum)
      (Platyhelminthes: Monogenea) infecting farmed barramundi, Lates calcarifer
      (Bloch). The effect of garlic extract (active component allicin) immersion on
      Neobenedenia sp. egg development, hatching success, oncomiracidia (larvae)
      longevity, infection success and juvenile Neobenedenia survival was examined and
      compared with freshwater and formalin immersion. Garlic extract was found to
      significantly impede hatching success (5% +/- 5%) and oncomiracidia longevity (<2
      h) at allicin concentrations of 15.2 MUL L(-1) , while eggs in the seawater
      control had >95% hatching success and mean oncomiracidia longevity of 37 +/- 3 h.
      At much lower allicin concentrations (0.76 and 1.52 MUL L(-1)), garlic extract
      also significantly reduced Neobenedenia infection success of L. calcarifer to 25%
      +/- 4% and 11% +/- 4%, respectively, compared with 55% +/- 7% in the seawater
      control. Juvenile Neobenedenia attached to host fish proved to be highly
      resistant to allicin with 96% surviving 1-h immersion in 10 mL L(-1) (15.2 MUL L(
      1) allicin) of garlic extract. Allicin-containing garlic extracts show potential
      for development as a therapy to manage monogenean infections in intensive
      aquaculture with the greatest impact at the egg and larval stages.

PMID- 23952606
TI  - Nano-nutrition of chicken embryos. The effect of silver nanoparticles and ATP on
      expression of chosen genes involved in myogenesis.
AB  - It has been suggested that the quantity and quality of nutrients stored in the
      egg might not be optimal for the fast rate of chicken embryo development in
      modern broilers, and embryos could be supplemented with nutrients by in ovo
      injection. Recent experiments showed that in ovo feeding reduces post-hatch
      mortality and skeletal disorders and increases muscle growth and breast meat
      yield. Adenosine triphosphate (ATP) is a "ready for use" energetic molecule,
      while nanoparticles of silver (Nano-Ag) may penetrate tissues as well as cells
      and localise inside cells. In this investigation, we hypothesised that silver
      nanoparticles could be used as a protective carrier for ATP as well as an active
      agent. ATP and/or an ATP complex with Nano-Ag would be delivered to the muscle
      cells as a gene expression regulator and promoter of growth and development of
      embryo breast muscle. A collection of 160 broiler eggs was randomly divided into
      a Control group without injection and injected groups with hydrocolloids of Nano
      Ag, ATP or a complex of Nano-Ag and ATP (Nano-Ag/ATP). The embryos were evaluated
      on day 20 of incubation. The results indicate that the application of ATP to
      chicken embryos increases expression of fibroblast growth factor 2 (FGF2),
      vascular endothelial growth factor (VEGF) and Na(+)/K(+) transporting ATPase
      (ATP1A1), which may indicate that an extra energy source can enhance molecular
      mechanisms of muscle cell proliferation. Nano-Ag also up-regulated expression of
      FGF2, VEGF, ATP1A1 and, also up-regulated expression of myogenic differentiation
      1(MyoD1), affecting cell differentiation. The results indicate that ATP and Nano
      Ag may accelerate growth and maturation of muscle cells. 

PMID- 23952607
TI  - European deciduous trees exhibit similar safety margins against damage by spring
      freeze events along elevational gradients.
AB  - Minimum temperature is assumed to be an important driver of tree species range
      limits. We investigated during which period of the year trees are most vulnerable
      to freezing damage and whether the pressure of freezing events increases with
      increasing elevation. We assessed the course of freezing resistance of buds and
      leaves from winter to summer at the upper elevational limits of eight deciduous
      tree species in the Swiss Alps. By reconstructing the spring phenology of these
      species over the last eight decades using a thermal time model, we linked
      freezing resistance with long-term minimum temperature data along elevational
      gradients. Counter-intuitively, the pressure of freeze events does not increase
      with elevation, but deciduous temperate tree species exhibit a constant safety
      margin (5-8.5 K) against damage by spring freeze events along elevational
      gradients, as a result of the later flushing at higher elevation. Absolute
      minimum temperatures in winter and summer are unlikely to critically injure
      trees. Our study shows that freezing temperatures in spring are the main
      selective pressure controlling the timing of flushing, leading to a shorter
      growing season at higher elevation and potentially driving species distribution
      limits. Such mechanistic knowledge is important to improve predictions of tree
      species range limits.

PMID- 23952608
TI  - Role of dietary polyphenols and inflammatory processes on disease progression
      mediated by the gut microbiota.
AB  - Mendelsohn and Larrick have recently discussed in a recent article in
      Rejuvenation Research that dietary modifications of the gut microbiota affect the
      risk for cardiovascular disease. In this context, dietary patterns and single
      specific nutrients appear to produce singular consequences on the gut microbiota,
      subsequently impacting on maintenance of well-being and disease onset or
      evolution, whose intimate influences and mechanisms are now starting to be
      disentangled. Thus, the consumption of dietary fiber and particular
      polysaccharides affects colonic fermentation processes involving short-chain
      fatty acid production, accompanying changes in the environmental pH, inhibiting
      Bacteroides spp., and rising levels of butyrate-producing Gram-positive bacteria.
      This scenario may contribute to the design of novel therapeutic approaches to
      manipulate gut microbiota to treat cardiovascular diseases and obesity. Indeed,
      cardiovascular risk may be indirectly dependent on pathways associated with
      microbe-induced obesity or diabetes through inflammation. Diverse components of
      the diet, including bioactive molecules with bactericidal functions, such as
      polyphenols, may play a role on intestinal mucosa inflammation and permeability
      and contribute to explaining the mutual interactions between obesity, diabetes,
      and adverse cardiovascular events.

PMID- 23952609
TI  - Rapid monitoring of immune reconstitution after allogeneic stem cell
      transplantation--a comparison of different assays for the detection of
      cytomegalovirus-specific T cells.
AB  - OBJECTIVES: Cytotoxic T cells (CTLs) play an important role in controlling
      cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell
      transplantation (HSCT). The purpose of this study was to compare four different
      assays to detect CMV antigen-specific T cells for the monitoring of CMV-specific
      immune reconstitution after HSCT. METHODS: Comparative monitoring of CMV-specific
      T cells was performed using HLA tetramer, interferon-gamma enzyme-linked
      immunospot (ELISPOT), intracellular IFN-gamma (IC-FACS), and real-time polymerase
      chain reaction (RT-PCR) assays with immunodominant CMV pp65-HLA-A2-restricted
      peptide and recombinant pp65-protein in 18 patients after allogeneic HSCT.
      RESULTS: Using pp65-peptide to stimulate T cells in HLA-A2-positive patients,
      antigen-specific T cells have been detected in 43% (10 of 23) by IC-FACS, 62% (13
      of 21) by tetramer, 68% (15 of 22) by RT-PCR, and 53% (10 of 19) by ELISPOT. No T
      cell responses were detected in HLA-A2-negative patients by all assays.
      Stimulating with combination of both pp65-peptide and pp65-protein detected 72%
      (18/25) by IC-FACS, 88% (22/25) by RT-PCR, and 59% (12/22) by ELISPOT. Comparing
      the different methods of T-cell detection we found a significant positive
      correlation between RT-PCR and tetramer analysis, IC flow cytometry and ELISPOT
      assay. Using pp65-protein for T-cell activation overcomes the HLA restriction of
      the HLA-A2-restricted pp65-peptide stimulation, thus increasing the detection
      limit of antigen-specific T cells. CONCLUSION: CMV-specific T cells have been
      most frequently detected using RT-PCR suggesting a higher sensitivity compared
      with IC-FACS, tetramer, and ELISPOT assays. This technique allows rapid and
      sensitive monitoring of CMV-specific immune reconstitution after HSCT, which
      could guide prophylactic and therapeutic strategies to avoid active CMV disease.

PMID- 23952611
TI  - NMR spectroscopic approach reveals metabolic diversity of human blood plasma
      associated with protein-drug interaction.
AB  - Although blood plasma has been used to diagnose diseases and to evaluate
      physiological conditions, it is not easy to establish a global normal
      concentration range for the targeting components in the plasma due to the
      inherent metabolic diversity. We show here that NMR spectroscopy coupled with
      principal component analysis (PCA) may provide a useful method for quantitatively
      characterizing the metabolic diversity of human blood plasma. We analyzed 70
      human blood plasma samples with and without addition of ibuprofen. By defining
      the PC score values as diversity index (I(div)) and the drug-induced PC score
      value change as interaction index (I(dist)), we find that the two indexes are
      highly correlated (P < 0.0001). Triglycerides, choline-containing phospholipids,
      lactate, and pyruvate are associated with both indexes (P < 0.0001),
      respectively. In addition, a significant amount of lactate and pyruvate are in
      the NMR "invisible" bound forms and can be replaced by ibuprofen. The diffusion
      and transverse relaxation time weighted NMR approaches gave rise to a better
      characterization of the diversity and the interaction than that of the one
      acquired using NOESYPR1D with 100 ms mixing time. These results might be useful
      for understanding the blood plasma-drug interaction and personalized therapy.

PMID- 23952610
TI  - The mTOR pathway and integrating immune regulation.
AB  - The mammalian target of rapamycin (mTOR) pathway is an important integrator of
      nutrient-sensing signals in all mammalian cells, and acts to coordinate the cell
      proliferation with the availability of nutrients such as glucose, amino acids and
      energy (oxygen and ATP). A large part of the immune response depends on the
      proliferation and clonal expansion of antigen-specific T cells, which depends on
      mTOR activation, and the pharmacological inhibition of this pathway by rapamycin
      is therefore potently immunosuppressive. It is only recently, however, that we
      have started to understand the more subtle details of how the mTOR pathway is
      involved in controlling the differentiation of effector versus memory CD8(+) T
      cells and the decision to generate different CD4(+) helper T-cell subsets. In
      particular, this review will focus on how nutrient sensing via mTOR controls the
      expression of the master transcription factor for regulatory T cells in order to
      maintain the balance between tolerance and inflammation. 

PMID- 23952612
TI  - Solution-processed zinc phosphide (alpha-Zn3P2) colloidal semiconducting
      nanocrystals for thin film photovoltaic applications.
AB  - Zinc phosphide (Zn3P2) is a promising earth-abundant material for thin film
      photovoltaic applications, due to strong optical absorption and near ideal band
      gap. In this work, crystalline zinc phosphide nanoparticles are synthesized using
      dimethylzinc and tri-n-octylphosphine as precursors. Transmission electron
      microscopy and X-ray diffraction data show that these nanoparticles have an
      average diameter of ~8 nm and adopt the crystalline structure of tetragonal alpha
      Zn3P2. The optical band gap is found to increase by 0.5 eV relative to bulk
      Zn3P2, while there is an asymmetric shift in the conduction and valence band
      levels. Utilizing layer-by-layer deposition of Zn3P2 nanoparticle films,
      heterojunction devices consisting of ITO/ZnO/Zn3P2/MoO3/Ag are fabricated and
      tested for photovoltaic performance. The devices are found to exhibit excellent
      rectification behavior (rectification ratio of 600) and strong photosensitivity
      (on/off ratio of ~10(2)). X-ray photoelectron spectroscopy and ultraviolet
      photoemission spectroscopy analyses reveal the presence of a thin 1.5 nm
      phosphorus shell passivating the surface of the Zn3P2 nanoparticles. This shell
      is believed to form during the nanoparticle synthesis. 

PMID- 23952614
TI  - Post-partum evaluation of maternal cardiac function after severe preeclampsia.
AB  - OBJECTIVE: To evaluate the post-partum maternal cardiac function in patients with
      history of severe preeclampsia. METHODS: A series of women with previous
      singleton pregnancy complicated by severe preeclampsia underwent transthoracic
      echocardiography at 6-12 months from delivery. A group of women with previous
      uncomplicated pregnancy was selected as controls. RESULTS: Sixteen women with
      history of severe preeclampsia were enrolled in the study group whereas 18
      patients were selected as controls. In the study group systolic (p=0.002) and
      diastolic blood pressure (p=0.044) were significantly higher. Significant
      differences were observed in systolic left ventricular (LV) parameters, such as
      cardiac output (p=0.034), LV mass indexed to BSA (p=0.024) and longitudinal
      contraction, expressed by tissue Doppler (TD) S1 wave, which resulted relatively
      impaired in former preeclamptic women (p=0.049). As regards as diastolic
      parameters, pulsed Doppler A-wave velocity was increased (p=0.036). TD E-wave
      velocity was significantly lower in study group (p<0.001) and E/E1 ratio (E=peak
      early diastole transmitral wave velocity/E1=peak early diastolic velocity at
      mitral valve annulus at TD) was higher respect to controls (p<0.001).
      CONCLUSIONS: LV contractility and diastolic function, although within normal
      reference ranges, show slight but significant impairment among women who
      experienced a severe preeclampsia. TD seems to be a sensible tool to identify
      these precocious signs of potential LV dysfunction.

PMID- 23952613
TI  - Characterization of interactions between heparin/glycosaminoglycan and adeno
      associated virus.
AB  - Adeno-associated virus (AAV) is a key candidate in the development of gene
      therapy. In this work, we used surface plasmon resonance spectroscopy to study
      the interaction between AAV and heparin and other glycosaminoglycans (GAGs).
      Surface plasmon resonance results revealed that heparin binds to AAV with an
      extremely high affinity. Solution competition studies showed that binding of AAV
      to heparin is chain length-dependent. AAV prefers to bind full chain heparin. All
      sulfo groups (especially N-sulfo and 6-O-sulfo groups) on heparin are important
      for the AAV-heparin interaction. Higher levels of sulfo group substitution in
      GAGs enhance their binding affinities. Atomic force microscopy was also performed
      to image AAV-2 in a complex with heparin. 

PMID- 23952615
TI  - Body mass index (BMI)-for-age and health-related quality of life (HRQOL) among
      high school students in Tehran.
AB  - BACKGROUND: The study aimed to determine the association between body mass index
      (BMI)-for-age and health-related quality of life (HRQOL) among high school
      students in Tehran. METHODS: A total of 465 high school students (227 girls and
      238 boys) and their parents were participated in this cross-sectional study. Body
      weight and height of the students were measured. For assessing HRQOL, both
      adolescent self-report and parent proxy-report of the Persian version of
      Pediatric Quality of Life Inventory (PedsQLTM4.0) questionnaire were completed by
      adolescents and their parents respectively. RESULTS: The prevalence of overweight
      and obesity (38.5%) was higher than severe thinness and thinness (2.8%). Mean of
      adolescent self-reported and parent proxy-reported HRQOL total score were 80.26
      +/- 12.07 and 81.30 +/- 14.08 respectively. In terms of HRQOL subscale scores,
      the highest subscale score of HRQOL was reported in social functioning (87.27 +/-
      14.40) and the lowest score was reported in emotional functioning (69.83 +/-
      18.69). Based on adolescent self-report, adolescent boys had significantly higher
      mean score for total and all subscale scores of HRQOL compared with girls (P <
      0.05). BMI-for-age was inversely correlated to adolescent self-reported HRQOL
      total score (r = -0.25, P < 0.05). Based on adolescents self-report, HRQOL total
      score was significantly different by body weight status (F = 16.16, P < 0.05).
      Normal weight adolescents had significantly higher HRQOL total score compared
      with overweight (mean difference: 7.32; P < 0.05) and obese adolescents (mean
      difference: 9.10, P < 0.05). The HRQOL total score was not significantly
      different between normal weight and underweight adolescents (mean difference:
      1.65, P = 0.96). However, based on parent proxy-reports, HRQOL total score was
      not significantly different by body weight status (F = 2.64, P = 0.059).
      CONCLUSION: More than one-third of adolescents were overweight and obese. BMI-for
      age was inversely correlated to adolescent self-reported HRQOL. Based on
      adolescents' perspective, overweight and obese adolescents had poorer HRQOL
      compared with normal weight adolescents. Intervention studies are needed to
      improve the HRQOL of overweight and obese adolescents in Tehran.

PMID- 23952616
TI  - How is Primary Health Care conceptualised in nursing in Australia? A review of
      the literature.
AB  - Australia, in common with many other countries, is expanding the role of Primary
      Health Care (PHC) to manage the growing burden of chronic disease and prevent
      hospitalisation. Australia's First National Primary Health Care Strategy released
      in 2010 places general practice at the centre of care delivery, reflecting a
      constitutional division of labour in which the Commonwealth government's primary
      means of affecting care delivery in this sector is through rebates for services
      delivered from the universal healthcare system Medicare. A review of Australian
      nursing literature was undertaken for 2006-2011. This review explores three
      issues in relation to these changes: How PHC is conceptualised within Australian
      nursing literature; who is viewed as providing PHC; and barriers and enablers to
      the provision of comprehensive PHC. A review of the literature suggests that the
      terms 'PHC' and 'primary care' are used interchangeably and that PHC is now
      commonly associated with services provided by practice nurses. Four structural
      factors are identified for a shift away from comprehensive PHC, namely fiscal
      barriers, educational preparation for primary care practice, poor role definition
      and interprofessional relationships. The paper concludes that while moves towards
      increasing capacity in general practice have enhanced nursing roles, current
      policy and the nature of private business funding alongside some medical
      opposition limit opportunities for Australian nurses working in general practice.

PMID- 23952617
TI  - Partial duplication of chromosome 19 associated with syndromic duane retraction
      syndrome.
AB  - BACKGROUND: To evaluate possible monogenic and chromosomal anomalies in a patient
      with unilateral Duane retraction syndrome, modest dysmorphism, cerebral white
      matter abnormalities, and normal cognitive function. MATERIALS AND METHODS:
      Performing high-resolution array comparative genomic hybridization (array CGH)
      and sequencing of HOXA1, KIF21A, SALL4, and CHN1 genes. RESULTS: The proband had
      unilateral Duane retraction syndrome (DRS) type III on the right with low-set
      ears, prominent forehead, clinodactyly, and a history of frequent infections
      during early childhood. Motor development and cognitive function were normal.
      Parents were not related, and no other family member was similarly affected. MRI
      revealed multiple small areas of high signal on T2 weighted images in cerebral
      white matter oriented along white matter tracts. Sequencing of HOXA1, KIF21A,
      SALL4, and CHN1 did not reveal any mutation(s). Array CGH showed a 95 Kb de novo
      duplication on chromosome 19q13.4 encompassing four killer cell immunoglobulin
      like receptor (KIR) genes. Conclusions. KIR genes have not previously been linked
      to a developmental syndrome, although they are known to be expressed in the human
      brain and brainstem and to be associated with certain infections and autoimmune
      diseases, including some affecting the nervous system. DRS and brain neuroimaging
      abnormalities may imply a central and peripheral oligodendrocyte abnormality
      related in some fashion to an immunomodulatory disturbance.

PMID- 23952618
TI  - Searching for closely related ligands with different mechanisms of action using
      machine learning and mapping algorithms.
AB  - Supervised machine learning approaches, including support vector machines, random
      forests, Bayesian classifiers, nearest-neighbor similarity searching, and a
      conceptually distinct mapping algorithm termed DynaMAD, have been investigated
      for their ability to detect structurally related ligands of a given receptor with
      different mechanisms of action. For this purpose, a large number of simulated
      virtual screening trials were carried out with models trained on mechanistic
      subsets of different classes of receptor ligands. The results revealed that
      ligands with the desired mechanism of action were frequently contained in
      database selection sets of limited size. All machine learning approaches
      successfully detected mechanistic subsets of ligands in a large background
      database of druglike compounds. However, the early enrichment characteristics
      considerably differed. Overall, random forests of relatively simple design and
      support vector machines with Gaussian kernels (Gaussian SVMs) displayed the
      highest search performance. In addition, DynaMAD was found to yield very small
      selection sets comprising only ~10 compounds that also contained ligands with the
      desired mechanism of action. Random forest, Gaussian SVM, and DynaMAD
      calculations revealed an enrichment of compounds with the desired mechanism over
      other mechanistic subsets.

PMID- 23952619
TI  - The dynamic changes of zinc transporter 8 autoantibodies in Czech children from
      the onset of Type 1 diabetes mellitus.
AB  - AIMS: The prevalence of autoantibodies to zinc transporter 8 (ZnT8) in Czech
      children at the onset of Type 1 diabetes mellitus and dynamic changes in ZnT8
      autoantibody levels during disease progression were studied. The value of ZnT8
      autoantibody measurements in diagnosis of Type 1 diabetes was assessed. METHODS:
      Serum samples from 227 children with newly diagnosed Type 1 diabetes and from 101
      control children without diabetes were analysed in a retrospective cross
      sectional study. One hundred and seventy-one samples from 116 of the patients
      with diabetes were analysed in a follow-up study at (median) intervals of 1, 3, 5
      and 10 years after onset of Type 1 diabetes. ZnT8 autoantibodies were measured
      using a bridging enzyme-linked immunosorbent assay, while antibodies to glutamic
      acid decarboxylase, insulinoma antigen 2 and insulin were measured by
      radioimmunoassays. RESULTS: ZnT8 autoantibodies were detected in 163/227 (72%) of
      children at Type 1 diabetes onset and in 1/101 (1%) of the control subjects.
      Sixteen out of 227 (7%) patients with Type 1 diabetes were antibody negative
      based on three antibodies (glutamic acid decarboxylase, insulinoma antigen 2 and
      insulin). This false-negative rate was reduced to 10/227 (4.4%) (P < 0.05) after
      inclusion of ZnT8 autoantibody measurements. Of the children, 142/227 (63%) were
      positive for at least three antibodies and the most common combination was
      insulinoma antigen 2, glutamic acid decarboxylase and ZnT8. ZnT8 autoantibody
      levels decreased over time after Type 1 diabetes onset and the presence and level
      of ZnT8 autoantibodies correlated with IA-2 autoantibodies. CONCLUSIONS: A ZnT8
      autoantibody enzyme-linked immunosorbent assay showed 72% disease sensitivity and
      99% specificity at Type 1 diabetes onset. Measurements of ZnT8 autoantibodies are
      important for Type 1 diabetes diagnosis and should be included in the panel of
      autoantibodies tested at the onset of Type 1 diabetes.

PMID- 23952620
TI  - Association between Alzheimer's disease and the NOS3 gene Glu298Asp polymorphism.
AB  - BACKGROUND: The Glu298Asp gene polymorphism in NOS3 gene has been extensively
      investigated for association to Alzheimer's disease (AD), however, results of
      different studies have been inconsistent. The objective of this study is to
      assess the relationship of NOS3 Glu298Asp polymorphism and AD risk by using meta
      analysis. METHODS: All eligible case-control studies were searched in PubMed and
      Embase. Odds ratios (OR) with the 95% confidence intervals (CI) were used to
      assess the association. RESULTS: A total of 5522 cases and 4877 controls in 20
      case-control studies were included. Obvious heterogeneity among studies was
      detected, and no significant association was observed between the NOS3 Glu298Asp
      polymorphism and AD risk. After exclusion of three studies, the heterogeneity
      disappeared and still no association was observed. In the subgroup analysis by
      ethnicity, we did not find any significant association between this polymorphism
      and AD risk in both Asians and Caucasians. CONCLUSIONS: This meta-analysis
      suggested that the NOS3 Glu298Asp gene polymorphism is not a strong risk factor
      for AD. To further evaluate gene-to-gene and gene-to-environmental interactions
      between polymorphisms of NOS3 gene and AD risk, more studies with large groups of
      patients are required.

PMID- 23952621
TI  - Hypovitaminosis D in dogs with spirocercosis.
AB  - BACKGROUND: Spirocercosis in dogs is characterized by esophageal nodules that can
      undergo neoplastic transformation. Hypovitaminosis D has been associated with
      neoplasia formation. We hypothesized hypovitaminosis D in neoplastic
      spirocercosis and that it could be a risk factor for neoplastic transformation.
      OBJECTIVE: To measure and compare vitamin D status, assessed by serum 25
      hydroxyvitamin D [25(OH)D] concentrations in non-neoplastic (n = 25) and
      neoplastic (n = 26) spirocercosis client-owned dogs and healthy dogs (n = 24).
      ANIMALS: Twenty-five non-neoplastic dogs, 26 neoplastic dogs, and 24 healthy
      dogs. METHODS: Fifty-one dogs were randomly selected from 119 dogs diagnosed with
      spirocercosis presenting to our hospital, and further divided into non-neoplastic
      or neoplastic groups. Exclusion criteria included dogs less than 1 year old, with
      concurrent diseases, received corticosteroids, or treated prophylactically for
      spirocercosis. Serum 25(OH)D concentration was measured by high-performance
      liquid chromatography. Spirocercosis dogs' appetites were graded and compared.
      RESULTS: Serum 25(OH)D concentrations were significantly different among all
      groups (P < .001). 25-Hydroxyvitamin D concentrations were significantly lower in
      neoplastic group (median 30.7 nmol/L [range 14.7-62.2]) compared to non
      neoplastic (median 52.7 nmol/L [range 19.1-129.7, P < .05]) and healthy groups
      (median 74.6 nmol/L [range 37.4-130.5, P < .005]). 25-hydroxyvitamin D
      concentrations were significantly lower in non-neoplastic spirocercosis dogs
      compared to healthy ones (P < .05). Neoplastic and non-neoplastic spirocercosis
      dogs had similar appetite scores (P = 1.0). 25-Hydroxyvitamin D concentrations
      were not significantly different between dogs with normal (P = .087) and abnormal
      (P = .125) appetites within neoplastic and non-neoplastic spirocercosis groups.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Further studies are warranted to determine
      potential use of vitamin D treatment in spirocercosis and explore role of
      hypovitaminosis D in pathogenesis of malignant transformation.

PMID- 23952623
TI  - Social networking sites in romantic relationships: attachment, uncertainty, and
      partner surveillance on facebook.
AB  - Social networking sites serve as both a source of information and a source of
      tension between romantic partners. Previous studies have investigated the use of
      Facebook for monitoring former and current romantic partners, but why certain
      individuals engage in this behavior has not been fully explained. College
      students (N=328) participated in an online survey that examined two potential
      explanatory variables for interpersonal electronic surveillance (IES) of romantic
      partners: attachment style and relational uncertainty. Attachment style predicted
      both uncertainty and IES, with preoccupieds and fearfuls reporting the highest
      levels. Uncertainty did not predict IES, however. Future directions for research
      on romantic relationships and online surveillance are explored.

PMID- 23952624
TI  - Use of instant messaging predicts self-report but not performance measures of
      inattention, impulsiveness, and distractibility.
AB  - We examined how young adults' use of instant messaging, text messaging, and
      traditional reading related to their self-reported experience of distractibility
      and impulsiveness and to their performance on computerized tasks designed to
      assess inattention and impulsive responses to visual stimuli. Participants
      reported their media use and completed self-report measures of impulsiveness
      (i.e., the Barratt Impulsiveness Scale) and distractibility for academic reading.
      They also completed performance based measures of inattention and impulsiveness
      using the Tests of Variables of Attention (T.O.V.A.((r))). Results demonstrated
      that instant message use was significantly related to higher levels of
      attentional impulsiveness and distractibility on the self-report measures, while
      traditional reading consistently predicted lower levels of impulsiveness and
      distractibility. However, media use was not significantly related to the
      performance measures of inattention and behavioral impulsiveness.

PMID- 23952625
TI  - The relationship between internet addiction and body mass index in Turkish
      adolescents.
AB  - The purpose of this study was to investigate Internet use patterns and Internet
      addiction among adolescents and to examine the correlation between Internet
      addiction and eating attitudes and body mass index (BMI). The study was conducted
      among 1,938 students, aged between 14 and 18 years. The Internet Addiction Test
      (IAT), the Eating Attitudes Test (EAT), and a sociodemographic query form were
      used to collect data. According to the IAT, 12.4% of the study sample met the
      criteria for Internet addiction. A significant positive correlation between BMI
      and the IAT (r=0.307; p<0.01) and weekly Internet use (r=0.215; p<0.01) was
      found. Nine students with Internet addiction (3.8%) and 90 with average Internet
      use (5.3%) were found to have a possible eating disorder (p>0.05). No
      relationship was found between the EAT and the IAT and duration of weekly
      Internet use. Linear regression analysis revealed a significant independent
      association of the IAT with BMI (r=0.235; p<0.001). These results indicate an
      association between Internet addiction and BMI. Further studies are needed to
      describe the causality of this association.

PMID- 23952626
TI  - Players' expertise and competition with others shape the satisfaction of
      competence needs, gaming gratifications, and contingent self-esteem in a gaming
      context.
AB  - The current study explores how competition and gaming expertise affect the
      satisfaction of competence needs and gaming gratifications. We demonstrate that
      competition moderates the effect of gaming expertise on the satisfaction of
      competence needs, which in turn affects game enjoyment and replay intention.
      Gaming expertise predicted players' need satisfaction, game enjoyment, and replay
      intention significantly better in a competitive compared to a noncompetitive
      context. The effect of gaming expertise on game enjoyment and replay intention
      was, furthermore, mediated by the satisfaction of competence needs. Finally,
      gaming expertise positively affected the importance of competition for players'
      self-esteem only in the competitive gaming context. The present findings
      demonstrate the importance of competition and gaming expertise for the
      satisfaction of competence needs, gaming gratifications, and the pursuit of self
      esteem during gameplay, attesting to the applicability of self-determination
      theory to gaming contexts.

PMID- 23952622
TI  - Developmental-like bone regeneration by human embryonic stem cell-derived
      mesenchymal cells.
AB  - The in vivo osteogenesis potential of mesenchymal-like cells derived from human
      embryonic stem cells (hESC-MCs) was evaluated in vivo by implantation on
      collagen/hydroxyapatite scaffolds into calvarial defects in immunodeficient mice.
      This study is novel because no osteogenic or chondrogenic differentiation
      protocols were applied to the cells prior to implantation. After 6 weeks, X-ray,
      microCT, and histological analysis showed that the hESC-MCs had consistently
      formed a highly vascularized new bone that bridged the bone defect and seamlessly
      integrated with host bone. The implanted hESC-MCs differentiated in situ to
      functional hypertrophic chondrocytes, osteoblasts, and osteocytes forming new
      bone tissue via an endochondral ossification pathway. Evidence for the direct
      participation of the human cells in bone morphogenesis was verified by two
      separate assays: with Alu and by human mitochondrial antigen positive staining in
      conjunction with co-localized expression of human bone sialoprotein in
      histologically verified regions of new bone. The large volume of new bone in a
      calvarial defect and the direct participation of the hESC-MCs far exceeds that of
      previous studies and that of the control adult hMSCs. This study represents a key
      step forward for bone tissue engineering because of the large volume,
      vascularity, and reproducibility of new bone formation and the discovery that it
      is advantageous to not over-commit these progenitor cells to a particular lineage
      prior to implantation. The hESC-MCs were able to recapitulate the mesenchymal
      developmental pathway and were able to repair the bone defect semi-autonomously
      without preimplantation differentiation to osteo- or chondroprogenitors. 

PMID- 23952627
TI  - The interdependence of family functioning and problematic internet use in a
      representative quota sample of adolescents.
AB  - Few studies have been carried out investigating the interdependence of family
      structures or interactions and excessive adolescent Internet use. In this study,
      we surveyed a representative German quota sample of 1,744 adolescents aged
      between 14 and 17 years with standardized questionnaires. Adolescents assessed
      their perceived own functioning in the family with the Self-Rating Scale (FB-S)
      of the German version of the Family Assessment Measure III, and reported on
      problematic Internet use with the Compulsive Internet Use Scale (CIUS). To
      predict problematic Internet use (CIUS summary score), we conducted a multiple
      stepwise linear regression analysis with the seven FB-S scales, the FB-S overall
      index, and gender and age as explanatory variables. For the full sample, a model
      with only one predictor (FB-S overall index) that summarizes the quality of
      family functioning produced a corrected coefficient of determination of 0.239 and
      explained variance of nearly 24%. t Test results for unpaired samples showed
      significant differences in the mean values of the FB-S scales and the FB-S
      overall index for comparisons of both sexes, as well as of a lower age group and
      higher age group. The prediction of problematic Internet use between both sexes
      and both age groups showed comparable findings (males: corrected coefficient of
      determination=0.288; females: corrected coefficient of determination=0.183; lower
      age group: corrected coefficient of determination=0.231; higher age group:
      corrected coefficient of determination=0.251), each with a single predictor (FB-S
      overall index). The results emphasize the importance of family functioning for
      the occurrence of problematic Internet use in adolescents.

PMID- 23952628
TI  - Response scale effects and integration processes in the averaging of motor
      movements.
AB  - In two experiments Ss averaged pairs of fixed, linear motor movements. A
      production method of motor averaging was used in Exp. 1, and category scaling
      procedures were used in Exp. 2. Stimulus interaction effects were found in Exp. 1
      but not in Exp. 2. Prior exposure to long or to short movements produced slight
      contrast effects in each experiment, but the nature of these effects differed
      between experiments. Results were interpreted within the context of averaging
      models of information integration theory. The implications of these models for
      theories of motor retention were discussed. 

PMID- 23952629
TI  - Effort scaling of isometric muscle contractions.
AB  - Maximum voluntary manual pull was measured on 18 Ss. These values were then used
      to determine the forces at 10% intervals from 30% to 100% of maximum strength for
      each S. In subsequent sessions, Ss started an exertion at one of these effort
      levels and then maintained an equal sensation of effort for 60 sec. The data at
      all 8 effort levels were closely approximated by triple-exponential decay
      functions. The percentage error between observed and calculated values ranged
      from 0.7% for the 100% effort data to 2.5% for the 20% condition. Since the
      function generated by a maximum voluntary contraction was not qualitatively
      different from the sub-maximal effort functions, it would seem that the fatigue
      curve may be viewed as a maximum effort function and, as such, involves the same
      processes that generate the lower intensity effort functions. 

PMID- 23952630
TI  - The effect of training on performance efficiency during a competitive isometric
      exercise.
AB  - Male college students (N = 15) participated in a competitive isometric exercise
      involving elbow flexion. The men were grouped into five teams each consisting of
      three men. A prize of $25 was offered to the team which maintained the greatest
      force for the longest time. Prior to the competitive session each S practiced
      individually on the apparatus for eight sessions. The men were randomly assigned
      to the teams on the day of the competition. During each session, continuous EMG
      recordings were made on the biceps muscle of the right arm. Training
      significantly improved both strength and endurance while reducing the average EMG
      amplitude. When team competition was introduced, there was a decrease in
      endurance and an increase in EMG amplitude, it was concluded that training
      improved muscular strength and endurance by increasing the efficiency of muscle
      utilization. Competition, even with a partially trained skill, was considered a
      stressful situation that produced an overexpenditure of muscle activity and a
      resulting decrease in performance. 

PMID- 23952631
TI  - Premotor and motor reaction time as a function of movement extent .
AB  - The effects of variations in extent of movement on fractionated reaction times
      (RTs) were studied in 18 male Ss. The means of total RT, premotor RT and motor RT
      (Weiss, 1965) did not change significantly under the two treatment conditions
      involving variations in extent of elbow flexion in response to a visual stimulus.
      These results supported earlier work of Brown and Slater-Hammel (1949), but
      apparently conflicted with recent data reported by Williams (1971). A
      differential effect of practice on the two tasks was identified and postulated as
      a possible factor contributing to the conflict among previous research findings. 

PMID- 23952632
TI  - Nature of perceived effort and fatigue.
AB  - Male Ss maintained handgrip contractions at constant perceived effort for 120-150
      sec. Force declined very rapidly during the first 45 sec. of contraction and much
      more slowly thereafter. Occlusion of blood flow had no effect on the early
      rapidly-declining portion of the constant-effort function, but accelerated the
      decline of the later portion. Occlusion impaired recovery from fatigue, but only
      slightly. The constant-effort function for the nonpreferred (weaker) hand
      declined more rapidly than that for the preferred (stronger) hand. Nevertheless,
      the difference in strength between the two hands was not reflected in feelings of
      effort in momentary contractions; submaximal loads, held for only 2 sec., did not
      appear more effortful when exerted with the weaker hand than with the stronger. 

PMID- 23952633
TI  - The post-kr interval.
AB  - The effect of a filled or unfilled post-KR interval during the acquisition phase
      of learning a blind positioning task was examined. The post-KR interval was
      either 2 or 30 sec., and was either unfilled or filled with a motor or verbal
      interpolated task. Ss were required to reach a learning criterion of three
      consecutive correct responses in positioning the arm to a 75 +/- 2 deg. criterion
      using a Kinesthesiometer while blindfolded. There was no effect on performance of
      either Length of the post-KR interval or Activity during the interval, but
      females performed significantly better than males. The results were discussed in
      terms of the relationship of motor STM theory to the acquisition process of
      learning a motor skill. 

PMID- 23952634
TI  - A comparison of the open and closed foot stance for reaction and movement times.
AB  - College males (N=150) were tested to determine the difference between the open
      and closed foot stance for RT and MT in various directions and under simple and
      choice stimulus conditions. Differences were found between the two foot stances
      depending upon the direction and type of stimulus employed. The results are
      discussed in regard to the direction and type of response S is required to
      utilize. 

PMID- 23952635
TI  - Predictive validation of single-episode uncomplicated depression as a benign
      subtype of unipolar major depression.
AB  - OBJECTIVE: To evaluate the predictive validity of a proposed benign major
      depressive disorder (MDD) subtype, single-episode 'uncomplicated MDD', defined as
      MDD that remits within 6 months and lacks severe impairment, psychotic ideation,
      suicidal ideation, psychomotor retardation, and feeling worthless. METHOD: Using
      two-wave National Epidemiologic Survey on Alcohol and Related Conditions data,
      four groups differing in wave 1 lifetime MDD history (no history [n = 27 609];
      single-episode uncomplicated [n = 418]; other single-episode [n = 1943]; multiple
      episode [n = 2473]) were evaluated for 3-year follow-up rates of major depressive
      episode (MDE), generalized anxiety disorder (GAD), and suicide attempt. RESULTS:
      Follow-up rates for no-MDD-history, single-episode uncomplicated MDD, other
      single-episode MDD, and multiple-episode MDD, respectively, were depressive
      episode 6.1%, 6.9%, 19.5%, 27.1%; GAD 2.7%, 4.3%, 7.8%, 11.2%; and suicide
      attempt 0.3%, 0.1%, 0.8%, 1.7%. For all validators, 3-year rates for single
      episode uncomplicated cases were not significantly different from no-MDD-history
      rates, but significantly lower than both single- and multiple-episode other-MDD
      rates. Mild MDD, defined by having only five or six symptoms, did not yield
      similarly benign results; logistic regression showed 'uncomplicated' provides
      incremental validity over 'mild' in explaining validator rates. Validator
      differences were not explainable by treatment-rate differences. CONCLUSION:
      Single-episode uncomplicated MDD is a benign subtype lacking typical MDD negative
      sequelae. The planned DSM-5.1 revision should reinstitute an extended bereavement
      exclusion applied to all stressors.

PMID- 23952637
TI  - Structure and chemical state of the Pt(557) surface during hydrogen oxidation
      reaction studied by in situ scanning tunneling microscopy and X-ray photoelectron
      spectroscopy.
AB  - The surface structure of Pt(557) during the catalytic oxidation of hydrogen was
      studied with in situ scanning tunneling microscopy and X-ray photoelectron
      spectroscopy. At 298 K, the surface Pt oxide formed after exposing Pt(557) to
      approximately 1 Torr of O2 can be readily removed by H2, at H2 partial pressures
      below 50 mTorr. Water is detected as the product in the gas phase, which also
      coadsorbs with hydroxyl groups on the Pt(557) surface. 

PMID- 23952636
TI  - A study to evaluate safety and tolerability of repeated doses of tirasemtiv in
      patients with amyotrophic lateral sclerosis.
AB  - Abstract Tirasemtiv is a fast skeletal muscle activator that increases the
      sensitivity of the sarcomere to calcium, increasing the efficiency of muscle
      contraction when the muscle is stimulated at submaximal contraction frequencies.
      A previous study showed single doses of tirasemtiv to be well tolerated and
      associated with potentially important improvements in a variety of functional
      outcomes. This study determined safety of tirasemtiv when given at doses up to
      500 mg daily for three weeks. Tirasemtiv was given as a single daily dose up to
      375 mg for two weeks, with and without concomitant riluzole. In a separate
      cohort, an ascending dose protocol evaluated a total dose of 500 mg daily given
      in two divided doses. Safety and tolerability were assessed, as well as measures
      of function, muscle strength and endurance. Results showed that tirasemtiv was
      well tolerated, with dizziness the most common adverse event. Tirasemtiv
      approximately doubled the serum concentration of riluzole. Trends were noted for
      improvement in ALSFRS-R, Maximum Minute Ventilation, and Nasal Inspiratory
      Pressure. In conclusion, tirasemtiv is well tolerated and can be given safely
      with a reduced dose of riluzole. Positive trends in multiple exploratory outcome
      measures support the further study of this agent in ALS. 

PMID- 23952638
TI  - In vitro evaluation of a novel topical cream for vitiligo and psoriasis that
      selectively delivers NB-UVB therapy when exposed to sunlight.
AB  - Ultraviolet-B (UVB) phototherapy is a well-established mode of treatment for
      several types of dermatological disease. For psoriasis and vitiligo, narrow band
      UVB (NB-UVB) phototherapy is an effective therapy, demonstrating greater efficacy
      and safety compared to broadband UVB or psoralen plus UVA treatments. While the
      treatment efficacy of NB-UVB artificial light sources is well documented, the
      long term time and cost commitment of the therapy remains a barrier to treatment
      adherence. Natural sunlight is an ideal source of accessible UVB radiation;
      however, exposure to natural sunlight generally results in erythema prior to the
      accumulation of sufficient dosage of therapeutic wavelengths of UVB. This
      communication describes a novel topical cream designed to selectively deliver NB
      UVB therapy when exposed to sunlight. The topical cream when combined with
      natural sunlight could offer patients a more convenient phototherapy option for
      psoriasis and vitiligo, potentially increasing patient compliance. 

PMID- 23952640
TI  - Comparison of two interpolation methods for empirical mode decomposition based
      evaluation of radiographic femur bone images.
AB  - Analysis of bone strength in radiographic images is an important component of
      estimation of bone quality in diseases such as osteoporosis. Conventional
      radiographic femur bone images are used to analyze its architecture using bi
      dimensional empirical mode decomposition method. Surface interpolation of local
      maxima and minima points of an image is a crucial part of bi-dimensional
      empirical mode decomposition method and the choice of appropriate interpolation
      depends on specific structure of the problem. In this work, two interpolation
      methods of bi-dimensional empirical mode decomposition are analyzed to
      characterize the trabecular femur bone architecture of radiographic images. The
      trabecular bone regions of normal and osteoporotic femur bone images (N = 40)
      recorded under standard condition are used for this study. The compressive and
      tensile strength regions of the images are delineated using pre-processing
      procedures. The delineated images are decomposed into their corresponding
      intrinsic mode functions using interpolation methods such as Radial basis
      function multiquadratic and hierarchical b-spline techniques. Results show that
      bi-dimensional empirical mode decomposition analyses using both interpolations
      are able to represent architectural variations of femur bone radiographic images.
      As the strength of the bone depends on architectural variation in addition to
      bone mass, this study seems to be clinically useful. 

PMID- 23952639
TI  - Biorecognition by DNA oligonucleotides after exposure to photoresists and resist
      removers.
AB  - Combining biological molecules with integrated circuit technology is of
      considerable interest for next generation sensors and biomedical devices. Current
      lithographic microfabrication methods, however, were developed for compatibility
      with silicon technology rather than bioorganic molecules, and consequently it
      cannot be assumed that biomolecules will remain attached and intact during on
      chip processing. Here, we evaluate the effects of three common photoresists
      (Microposit S1800 series, PMGI SF6, and Megaposit SPR 3012) and two photoresist
      removers (acetone and 1165 remover) on the ability of surface-immobilized DNA
      oligonucleotides to selectively recognize their reverse-complementary sequence.
      Two common DNA immobilization methods were compared: adsorption of 5'-thiolated
      sequences directly to gold nanowires and covalent attachment of 5'-thiolated
      sequences to surface amines on silica coated nanowires. We found that acetone had
      deleterious effects on selective hybridization as compared to 1165 remover,
      presumably due to incomplete resist removal. Use of the PMGI photoresist, which
      involves a high temperature bake step, was detrimental to the later performance
      of nanowire-bound DNA in hybridization assays, especially for DNA attached via
      thiol adsorption. The other three photoresists did not substantially degrade DNA
      binding capacity or selectivity for complementary DNA sequences. To determine
      whether the lithographic steps caused more subtle damage, we also tested
      oligonucleotides containing a single base mismatch. Finally, a two-step
      photolithographic process was developed and used in combination with
      dielectrophoretic nanowire assembly to produce an array of doubly contacted,
      electrically isolated individual nanowire components on a chip. Postfabrication
      fluorescence imaging indicated that nanowire-bound DNA was present and able to
      selectively bind complementary strands. 

PMID- 23952641
TI  - Theoretical study of water oxidation by the ruthenium blue dimer. II. Proton
      relay chain mechanism for the step [bpy2(HOO)Ru(IV)ORu(IV)(OH)bpy2]4+ ->
      [bpy2(O2(-))Ru(IV)ORu(III)(OH2)bpy2]4+.
AB  - The oxidation of water to O2 by the oxidized species [L2(O)Ru(V)ORu(V)(O)L2]4+ of
      the Ru blue dimer catalyst (L = bpy, bipyridine) is examined using density
      functional theory with model ligands and explicit solvent approaches. Following
      our earlier study of the initial O-O formation by addition of water (step I) ( J.
      Phys. Chem. A 2011, 115, 8003), we report calculations on the subsequent,
      penultimate step in the superoxide production (denoted step II), involving proton
      transfer from the reactant [L2(HOO)Ru(IV)ORu(IV)(OH)L2]4+ to form [L(O2(
      ))Ru(IV)ORu(III)(H2O)L2]4+. The reaction profile of step II commences with a
      rearrangement of the HOO and OH groups and associated solvent relaxation in the
      complex, accompanied by a barrier of ~9 kcal/mol and a free-energy change of +3
      kcal/mol. Subsequently, a water molecule connecting these two groups mediates a
      double proton transfer in a proton relay chain that proceeds spontaneously with a
      free-energy decrease of 8 kcal/mol to form step II's product. Comparison with
      other calculations is made, and the implications for the overall water oxidation
      to O2 are discussed.

PMID- 23952642
TI  - Effects of dietary supplementation of Bacillus amyloliquefaciens CECT 5940 and
      Enterococcus faecium CECT 4515 in adult healthy dogs.
AB  - The aim of this study was to evaluate the effect of a probiotic preparation
      consisting of two probiotic strains, Bacillus amyloliquefaciens CECT 5940 and
      Enterococcus faecium CECT 4515 (each 5 . 10(8) CFU/g feed), on faecal
      consistency, faecal microbiology and nutrient digestibility in adult healthy
      dogs. Sixteen beagles (eight males and eight females) were divided into two
      groups: the Control group (CON), which was fed the basal diet, and the probiotic
      group (PRO), which received the basal diet supplemented daily with 1 . 10(8) CFU
      for 39 consecutive days. Faecal score was assessed before (BS) and throughout the
      supplementation period (SP). Fresh faecal samples were collected before
      supplementation, before finishing the supplementation period and after 6 days of
      withdrawal for microbial enumeration and pH measurement. During the
      supplementation period, a digestibility trial was performed. There were no
      differences in faecal scores or the digestibility coefficients between groups.
      Between groups no statistical differences were found in most microbiota analysed
      or in faecal pH. However, during the supplementation period, pathogenic
      clostridia dropped significantly in Group PRO (5.64 vs. 2.94 +/- 0.53 CFU/g
      faeces; p < 0.001), when compared with the period BS. The use of the probiotic
      preparation had no impact on nutrient digestibility by adult healthy dogs;
      however, it could stabilise faecal microbiota by decreasing pathogenic
      clostridia. 

PMID- 23952643
TI  - Scale dependence in the effects of leaf ecophysiological traits on
      photosynthesis: Bayesian parameterization of photosynthesis models.
AB  - Relationships between leaf traits and carbon assimilation rates are commonly used
      to predict primary productivity at scales from the leaf to the globe. We
      addressed how the shape and magnitude of these relationships vary across
      temporal, spatial and taxonomic scales to improve estimates of carbon dynamics.
      Photosynthetic CO2 and light response curves, leaf nitrogen (N), chlorophyll
      (Chl) concentration and specific leaf area (SLA) of 25 grassland species were
      measured. In addition, C3 and C4 photosynthesis models were parameterized using a
      novel hierarchical Bayesian approach to quantify the effects of leaf traits on
      photosynthetic capacity and parameters at different scales. The effects of plant
      physiological traits on photosynthetic capacity and parameters varied among
      species, plant functional types and taxonomic scales. Relationships in the
      grassland biome were significantly different from the global average. Within
      species variability in photosynthetic parameters through the growing season could
      be attributed to the seasonal changes of leaf traits, especially leaf N and Chl,
      but these responses followed qualitatively different relationships from the
      across-species relationship. The results suggest that one broad-scale
      relationship is not sufficient to characterize ecosystem condition and change at
      multiple scales. Applying trait relationships without articulating the scales may
      cause substantial carbon flux estimation errors. 

PMID- 23952644
TI  - Fluorescent labeling and characterization of cellulose nanocrystals with varying
      charge contents.
AB  - Cotton-source cellulose nanocrystals (CNCs) with a range of surface charge
      densities were fluorescently labeled with 5-(4, 6-dichlorotriazinyl)
      aminofluorescein (DTAF) in a facile, one-pot reaction under alkaline conditions.
      Three CNC samples were labeled: (I) anionic CNCs prepared by sulfuric acid
      hydrolysis with a sulfur content of 0.47 wt %, (II) a partially desulfated,
      sulfuric acid-hydrolyzed CNC sample, which was less anionic with an intermediate
      sulfur content of 0.21 wt %, and (III) uncharged CNCs prepared by HCl hydrolysis.
      The DTAF-labeled CNCs were characterized by dynamic light scattering, atomic
      force microscopy, fluorescence spectroscopy and microscopy, and polarized light
      microscopy. Fluorescent CNCs exhibited similar colloidal stability to the
      starting CNCs, with the exception of the HCl-hydrolyzed sample, which became less
      agglomerated after the labeling reaction. The degree of labeling depended on the
      sulfur content of the CNCs, indicating that the presence of sulfate half-ester
      groups on the CNC surfaces hindered labeling. The labeling reaction produced CNCs
      that had detectable fluorescence, without compromising the overall surface
      chemistry or behavior of the materials, an aspect relevant to studies that
      require a fluorescent cellulose substrate with intact native properties. The DTAF
      labeled CNCs were proposed as optical markers for the dispersion quality of CNC
      loaded polymer composites. Electrospun polyvinyl alcohol fibers loaded with DTAF
      labeled CNCs appeared uniformly fluorescent by fluorescence microscopy,
      suggesting that the nanoparticles were well dispersed within the polymer matrix. 

PMID- 23952645
TI  - MHC class IIalpha alleles associated with resistance to Aeromonas hydrophila in
      purse red common carp, Cyprinus carpio Linnaeus.

PMID- 23952646
TI  - Schooling and variation in the COMT gene: the devil is in the details.
AB  - BACKGROUND: Schooling is considered one of the major contributors to the
      development of intelligence within societies and individuals. Genetic variation
      might modulate the impact of schooling and explain, at least partially, the
      presence of individual differences in classrooms. METHOD: We studied a sample of
      1,502 children (mean age = 11.7 years) from Zambia. Approximately 57% of these
      children were enrolled in school, and the rest were not. To quantify genetic
      variation, we investigated a number of common polymorphisms in the catechol-O
      methyltransferase (COMT) gene that controls the production of the protein thought
      to account for >60% of the dopamine degradation in the prefrontal cortex.
      RESULTS: Haplotype analyses generated results ranging from the presence to
      absence of significant interactions between a number of COMT haplotypes and
      indicators of schooling (i.e., in- vs. out-of-school and grade completed) in the
      prediction of nonverbal intelligence, depending on the parameter specification.
      However, an investigation of the distribution of corresponding p-values suggested
      that these positive results were false. CONCLUSIONS: Convincing evidence that the
      variation in the COMT gene is associated with individual differences in nonverbal
      intelligence either directly or through interactions with schooling was not
      found. p-values produced by the method of testing for haplotype effects employed
      here may be sensitive to parameter settings, invalid under default settings, and
      should be checked for validity through simulation.

PMID- 23952647
TI  - Effect of recombinant human soluble thrombomodulin on clinical outcomes of
      patients with coagulopathy after hematopoietic stem cell transplantation.
AB  - From 2001 to 2012, 71 individuals with hematological diseases received HSCT in
      our institution. Of these, 41 developed disseminated intravascular coagulation
      (DIC) in association with various underlying conditions. The patients who
      developed DIC after 2008 (n = 23) were treated by recombinant human soluble
      thrombomodulin (rTM), and the others (n = 11) were treated by either heparin
      and/or antithrombin III concentrate. Seven patients did not receive any
      anticoagulant therapy. Of note, treatment for coagulopathy by rTM significantly
      improved clinical outcomes of patients at day 100 and dramatically prolonged
      their overall survival (P = 0.044). Taken together, rTM is useful to improve
      clinical outcomes of transplant recipients with coagulopathy.

PMID- 23952648
TI  - Fast and accurate quantitation of glucans in complex mixtures by optimized
      heteronuclear NMR spectroscopy.
AB  - Nuclear magnetic resonance (NMR) spectroscopy is a widely used technique for
      mixture analysis, but it has shortcomings in resolving carbohydrate mixtures due
      to the narrow chemical shift range of glycans in general and fragments of
      homopolymers in particular. Here, we suggest a protocol toward fast spectroscopic
      glycan mixture analysis. We show that a plethora of oligosaccharides comprising
      only alpha-glucopyranosyl residues can be resolved into distinct quantifiable
      signals with NMR experiments that are substantially faster than chromatographic
      runs. Conceptually, the approach fully exploits the narrow line widths of glycans
      (nu1/2 < 3 Hz) in the (13)C spectral dimension while disregarding superfluous
      spectral information in compound identification and quantitation. The acetal
      (H1C1) groups suffice to spectroscopically resolve ~20 different starch fragments
      in optimized (1)H-(13)C NMR with a narrow (13)C spectral width (3 ppm) that
      allows sampling the indirect (13)C dimension at high resolution within 15 min.
      Rapid quantitations by high-resolution NMR data are achieved for glycans at
      concentrations as low as 10 MUg/mL. For validation, comparisons were made with
      quantitations obtained by more time-consuming chromatographic methods and yielded
      coefficients of determination (R(2)) above 0.99. 

PMID- 23952649
TI  - Scrub typhus associated acute kidney injury--a study from a tertiary care
      hospital from western Himalayan State of India.
AB  - OBJECTIVE: To report the clinical profile of acute kidney injury (AKI) associated
      with scrub typhus. METHODS: Retrospective study of hospitalized patients of acute
      febrile illness who were diagnosed scrub typhus and had AKI. RESULTS: 174 (35%)
      patients (75.9% female), mean age (41.4 +/- 15.9 years) were studied. The
      laboratory abnormalities were: anemia (63.2%), leukocytosis (44.3%),
      thrombocytopenia (61.5%), hyponatremia (35.6%), hypernatremia (2.9%), and
      hypokalemia (12.1%), hyperkalemia (11.5%), hypoalbuminemia (56.9%), hepatic
      dysfunction (70%) and metabolic acidosis (28.7%). The complications of
      hypotension (5.7%), septic shock (3.4%), pneumonia (10.9%), acute respiratory
      distress syndrome (ARDS) (11.5%), meningoencephalitis (6.9%), encephalopathy
      (5.2%), gastrointestinal bleed (1.3%), myocarditis (3.4%), disseminated
      intravascular coagulation (2.9%) and multi organ failure (MOF) (10.3%) developed
      during course of hospitalization in these patients. Twenty-five (14.4%) patients
      required intensive care support (ICU) support and seven (4%) patients were
      dialyzed. 146 (83.9%) patients survived. Twenty-eight (16.1%) patients died.
      There was a significant difference in the age, various hematological &
      biochemical abnormalities, complications and need for ICU support in the non
      survival group as compared the survival group. CONCLUSION: This study shows that
      AKI in scrub typhus is common and a severe disease. Age, a shorter hospital stay,
      severities of leukocytosis, thrombocytopenia, azotemia, hypoalbuminemia, hepatic
      dysfunction and the complications of ARDS, encephalopathy, MOF and need for ICU
      support are the factors associated with mortality.

PMID- 23952650
TI  - Third trimester fetal demise occurring at time of delivery: correlation of
      autopsy findings and placental pathology with emphasis on antenatal central
      nervous system injury.
AB  - OBJECTIVE: Third trimester fetal deaths occurring in the hospital at the time of
      delivery are unusual. We report an autopsy series of such cases with emphasis on
      neuropathological injury and other lesions predating delivery. METHODS: We
      identified autopsies performed on third trimester fetuses documented to be alive
      shortly before delivery, but that expired during, or very close to, time of
      delivery, and we correlate autopsy and placental findings. Fetuses with major
      congenital anomalies were excluded. RESULTS: Ten cases were identified (6 term, 4
      preterm). All were delivered by cesarean section and had attempted resuscitation.
      Established or recent brain injury was identified in 9 of 10 cases, including 3
      with established neuronal damage and 1 with periventricular leukomalacia.
      Additional autopsy findings included thymic involution in eight (five mild; three
      severe), myocardial infarcts in two; intrathoracic petechiae in five, and ascites
      or pleural or pericardial effusions in six. Severe thymic involution and
      myocardial infarcts correlated with established brain injury. Placental lesions
      adaptive to decreased oxygenation (increased nucleated red blood cells or villous
      hypervascularity) were seen in five cases and correlated with established brain
      injury. Acute chorioamnionitis with funisitis was present in one, and chronic
      inflammatory placental lesions were present in six. CONCLUSIONS: These findings
      indicate brain injury predated the time period immediately before delivery in 9
      of 10 fetuses, and in the fetuses with established brain injury the onset of
      acute illness was possibly >72 h before delivery.

PMID- 23952651
TI  - Performance validation of chromogenic coliform agar for the enumeration of
      Escherichia coli and coliform bacteria.
AB  - The performance of chromogenic coliform agar (CCA) for the enumeration of
      Escherichia coli and coliform bacteria was validated according to ENV ISO 13843
      using pure cultures and naturally contaminated water samples. The results
      indicate that for the detection of E. coli and coliform bacteria, respectively,
      the method is sensitive (94 and 91%), specific (97 and 94%), selective
      (selectivity -0.78 and -0.32) and efficient (96 and 92%). Relative recovery of E.
      coli and coliform bacteria on CCA in comparison with tryptone soy agar (TSA) was
      good (104 and 94% in mean, >80 and >70% in all cases), and repeatability and
      reproducibility were sufficient. The linear working range was defined for 10-100
      total target colonies per 47-mm membrane filter. A high precision of the method
      was confirmed by low overdispersion in comparison with Poisson distribution. The
      robustness of the method with respect to the variable incubation time of 21 +/- 3
      h was found to be low, because an incidental increase in presumptive colonies
      especially between 18 and 21 h was observed. In conclusion, the CCA method was
      proved as a reliable method for the quantification of E. coli and coliform
      bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: The international standard for
      the detection and enumeration of E. coli and coliform bacteria by membrane
      filtration (ISO 9308-1) is currently under revision and will be published in
      2014. In the new standard, lactose-triphenyl tetrazolium chloride (TTC) agar will
      be replaced by a CCA. A performance validation of this revised method according
      to ENV ISO 13843 is presented in this study to determine fundamental data on its
      applicability and to provide reference data for secondary validation by users of
      this method.

PMID- 23952652
TI  - Involvement of the glutamate receptor AtGLR3.3 in plant defense signaling and
      resistance to Hyaloperonospora arabidopsidis.
AB  - Like their animal counterparts, plant glutamate receptor-like (GLR) homologs are
      intimately associated with Ca(2+) influx through plasma membrane and participate
      in various physiological processes. In pathogen-associated molecular patterns
      (PAMP)-/elicitor-mediated resistance, Ca(2+) fluxes are necessary for activating
      downstream signaling events related to plant defense. In this study,
      oligogalacturonides (OGs), which are endogenous elicitors derived from cell wall
      degradation, were used to investigate the role of Arabidopsis GLRs in defense
      signaling. Pharmacological investigations indicated that GLRs are partly involved
      in free cytosolic [Ca(2+)] ([Ca(2+)]cyt) variations, nitric oxide (NO)
      production, reactive oxygen species (ROS) production and expression of defense
      related genes by OGs. In addition, wild-type Col-0 plants treated with the
      glutamate-receptor antagonist 6,7-dinitriquinoxaline-2,3-dione (DNQX) had a
      compromised resistance to Botrytis cinerea and Hyaloperonospora arabidopsidis.
      Moreover, we provide genetic evidence that AtGLR3.3 is a key component of
      resistance against H. arabidopsidis. In addition, some OGs-triggered immune
      events such as defense gene expression, NO and ROS production are also to
      different extents dependent on AtGLR3.3. Taken together, these data provide
      evidence for the involvement of GLRs in elicitor/pathogen-mediated plant defense
      signaling pathways in Arabidopsis thaliana.

PMID- 23952653
TI  - Examining day centre provision for older people in the UK using the Equality Act
      2010: findings of a scoping review.
AB  - This article reports the findings from a literature review of day care services
      undertaken during March-June 2012 and repeated in May 2013. The databases
      searched included AgeInfo, Embase, Medline, PsycINFO, Social Care Online, Web of
      Science and the publication platform Ingenta Connect as well as specialist older
      people's sites. It discusses these findings in the context of services for older
      people in the UK, defined as those aged 65 years and over. The aim of the scoping
      review was to identify what is known about how day services (here confined to
      congregate day care or day centres) will meet the challenges posed by the
      Equality Act 2010 in supporting different user groups, such as lesbian, gay,
      bisexual and transgender older people or older people from minority ethnic
      groups. The review found that research on all aspects of day services was limited
      and that information about older people using such services was often provided
      context-free. It concludes that those funding or evaluating day services' support
      to diverse groups of older people need to urgently address matters such as
      differential access and differential views about specific services. 

PMID- 23952654
TI  - Malignant potential of small oncocytic follicular carcinoma/Hurthle cell
      carcinoma: an institutional experience.
AB  - AIMS: Oncocytic follicular carcinoma/Hurthle cell carcinoma (OFCA/HCCA) is a rare
      tumour of the thyroid gland that can be associated with an aggressive clinical
      course. Most OFCA/HCCAs are large; however, tumours <=20 mm can occur. The aim of
      this study was to report our experience with OFCA/HCCA diagnosed at our
      institution. METHODS AND RESULTS: One hundred and nineteen cases of OFCA/HCCA
      were included in this study. Data points included age, sex, size of tumour,
      method of diagnosis, lymph node (LN) status, and clinical follow-up. The cohort
      included 37 males and 82 females (average age: 55 years). Preoperative fine
      needle aspiration (FNA) was performed in 73 (61%) cases. Twenty-five (21%)
      tumours measured <=20 mm and 94 (79%) measured >20 mm. Angioinvasion (AI) was
      present in 48 (40%) cases, and LN metastases (LNMs) in seven (6%) cases; of
      these, eight (17%) with AI and 1 (2%) with LNMs measured <=20 mm. Clinical follow
      up was available in 74 (62%) cases (range 12-144 months); 13 (17.5%) developed
      LNMs and six (8%) regional recurrence. Distant metastases (DMs) were seen in 12
      (16%) cases. Two cases with DMs and two with LN recurrence measured <=20 mm.
      CONCLUSIONS: Oncocytic follicular carcinoma/Hurthle cell carcinoma (OFCA/HCCA)
      can present as small (<=20 mm) tumours, and can be associated with AI, LNM, and
      DM.

PMID- 23952655
TI  - Toll-like receptor 4 gene Asp299Gly polymorphism in ischemic cerebrovascular
      disease: a meta-analysis.
AB  - Epidemiological studies have evaluated the association between Toll-like receptor
      4 (TLR4) gene Asp299Gly (rs4986790) polymorphism and the risk of ischemic
      cerebrovascular disease, but the results are inconsistent. In an effort to
      clarify earlier inconclusive results, a meta-analysis was performed. We searched
      the PubMed, Web of Science, Embase, Cochrane database, Clinicaltrials.gov,
      Current Controlled Trials, CNKI, CBMdisc, Chinese Clinical Trial Registry and
      Google Scholar until up to 20 July 2013. Additionally, hand searching of the
      references of identified articles was performed. Original observational studies
      investigating the association between TLR4 gene Asp299Gly polymorphism and
      ischemic cerebrovascular disease risk were included. All statistical analyses
      were performed using Stata 11.0. The search strategy identified 1038 potentially
      relevant articles, seven of which were included in the final meta-analysis,
      covering a total of 1767 cases and 2785 controls. Overall, no significant
      association was found between TLR4 gene Asp299Gly polymorphism and ischemic
      cerebrovascular disease risk (for G allele versus A allele: OR = 0.95, 95% CI =
      0.75-1.21, p = 0.69; for G/G+A/G versus A/A: OR = 0.96, 95% CI = 0.75-1.22, p =
      0.73). In addition, the similar results were obtained in the sensitivity analysis
      based on studies with the high quality. In summary, the present meta-analysis
      indicates that TLR4 gene Asp299Gly polymorphism is not associated with increased
      ischemic cerebrovascular disease risk. 

PMID- 23952656
TI  - Influence of peripheral vascular calcification on efficiency of screening tests
      for peripheral arterial occlusive disease in diabetes--a cross-sectional study.
AB  - AIMS: Pulse palpation and ankle brachial index are recommended to screen for
      peripheral arterial occlusive disease in people with diabetes. However, vascular
      calcification can be associated with false negative tests (arteriopathy present
      despite normal screening tests). We therefore studied the impact of peripheral
      vascular calcification on the performance of these tests. METHODS: This cross
      sectional study included 200 people with diabetes at high risk of cardiovascular
      disease. The main exclusion factor was an estimated glomerular filtration rate <
      30 ml/min. Peripheral arterial occlusive disease was diagnosed by colour duplex
      ultrasonography and peripheral vascular calcification scored by computed
      tomography scan. We measured sensitivity, specificity, predictive values,
      accuracy and likelihood ratios of pulse palpation and ankle brachial index, and
      looked for the impact of calcification on false negative tests (arteriopathy
      present despite normal screening tests). RESULTS: Ankle brachial index alone had
      poor sensitivity and negative predictive value and high negative likelihood
      ratio. Pulse palpation had higher sensitivity and negative predictive value. An
      abnormal pulse palpation, defined by weak or missing pulses, combined with an
      abnormal ankle brachial index, had the highest sensitivity and negative
      predictive value (92.3 and 89.8%, respectively). Vascular calcification score was
      higher in patients with false negative tests, for both pulse palpation and ankle
      brachial index (P < 0.0001 for all). Ankle systolic blood pressure was higher in
      patients with false negative tests for pulse palpation (P = 0.004). CONCLUSIONS:
      Below-knee vascular calcification gave a high rate of false negative results for
      ankle brachial index. Refined pulse palpation combined with ankle brachial index
      remained the best strategy to screen for peripheral arteriopathy.

PMID- 23952657
TI  - Oliver-McFarlane syndrome in a chinese boy: retinitis pigmentosa, trichomegaly,
      hair anomalies and mental retardation.
AB  - We report a male patient with retinitis pigmentosa, growth failure, long
      eyelashes, and sparse hair, which are typical signs of Oliver-McFarlane syndrome.
      The patient was born to healthy parents and developed night blindness at 2 years
      of age. Retinitis pigmentosa was diagnosed when he was 5 years old. To date, only
      11 cases of Oliver-McFarlane syndrome have been documented, with the present case
      being the 12th overall and the first in China. Thus, the existence of typical
      Oliver-McFarlane syndrome in Asians was verified.

PMID- 23952658
TI  - Accounting for target flexibility and water molecules by docking to ensembles of
      target structures: the HCV NS5B palm site I inhibitors case study.
AB  - The introduction of new anti-HCV drugs in therapy is an imperative need and is
      necessary with a view to develop an interferon-free therapy. Thus, the discovery
      and development of novel small molecule inhibitors of the viral NS5B polymerase
      represent an exciting area of research for many pharmaceutical companies and
      academic groups. This study represents a contribution to this field and relies on
      the identification of the best NS5B model(s) to be used in structure-based
      computational approaches aimed at identifying novel non-nucleoside inhibitors of
      one of the protein allosteric sites, namely, palm site I. First, the NS5B
      inhibitors at palm site I were classified as water-mediated or nonwater-mediated
      ligands depending on their ability to interact with or displace a specific water
      molecule. Then, we took advantage of the available X-ray structures of the
      NS5B/ligand complexes to build different models of protein/water combinations,
      which were used to investigate the influence on docking studies of solvent sites
      as well as of the influence of the protein conformations. As the overall trend,
      we observed improved performance in the docking results of the water-mediated
      inhibitors by inclusion of explicit water molecules, with an opposite behavior
      generally happening for the nonwater-mediated inhibitors. The best performing
      target structures for the two ligand sets were then used for virtual screening
      simulations of a library containing the known NS5B inhibitors along with related
      decoys to assess the best performing targets ensembles on the basis of their
      ability to discriminate active and inactive compounds as well as to generate the
      correct binding modes. The parallel use of different protein structures/water
      sets outperformed the use of a single target structure, with the two-protein
      3H98/2W-2FVC/7W and 3HKY/NoW-3SKE/NoW models resulting in the best performing
      ensembles for water-mediated inhibitors and nonwater-mediated inhibitors,
      respectively. The information gathered from this work confirms the primary role
      of water molecules and protein flexibility in docking-based studies and can be
      exploited to aid NS5B-directed HCV drug discovery efforts. 

PMID- 23952659
TI  - Amino acid, iodine, selenium, and coat color status among hyperthyroid, Siamese,
      and age-matched control cats.
AB  - BACKGROUND: Hyperthyroidism is common among older cats, but its pathogenesis
      remains poorly understood. Siamese and Himalayan cats have a reduced risk of
      hyperthyroidism compared with domestic short-hair cat breeds. A mechanism of risk
      reduction in pointed-coat breeds is unknown. OBJECTIVES: To determine if
      tyrosine, phenylalanine, iodine, or selenium blood concentrations are altered in
      hyperthyroid cats and to describe the plasma amino acid profiles of client-owned
      cats with naturally occurring hyperthyroidism. ANIMALS: Twenty-seven client-owned
      cats with (n = 12) and without (n = 15) hyperthyroidism were studied. METHODS:
      Cross-sectional study. Hyperthyroid cats were prospectively recruited among cats
      presenting for radioiodine therapy. Control cats were recruited among pets of
      hospital personnel. Blood was collected for total thyroxine, plasma amino acid,
      selenium, and iodine determination. Coat color (8 white or pointed; 19 dark),
      breed, and diet history were recorded. RESULTS: Tyrosine, phenylalanine, iodine,
      and selenium levels were not significantly different among light or dark cats or
      cats with or without hyperthyroidism (P > .05). Plasma amino acid profiles of
      hyperthyroid cats and control cats were similar, and neither group was deficient
      in any of the amino acids. L-glutamine was significantly lower in cats with
      hyperthyroidism (mean +/- SD: 648 +/- 193) compared with control cats (816 +/-
      134; P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Altered tyrosine, iodine, and
      selenium metabolism were not associated with coat color or hyperthyroidism in
      pointed or light coat-colored cats.

PMID- 23952660
TI  - Is major depression that major?

PMID- 23952661
TI  - Flight feedback and learning a projectile task.
AB  - Over KR acquisition trials of projecting an object a criterion distance, the
      hypotheses were tested that feedback from the flight of a projected object
      (flight feedback) would facilitate response recognition but not recall. Visual
      and auditory flight feedback variables each had two levels, flight feedback
      present or absent, forming a 2 * 2 * 61 trials design with 14 Ss per cell.
      Results supported the hypotheses, with flight flight feedback not facilitating
      response recall, though both flight feedback variables were strong determinants
      of response recognition. This latter finding was qualified by a discussion of the
      distinction between response recognition and recognition of response outcome. 

PMID- 23952662
TI  - Pursuit rotor reminiscence in schizophrenics and normals.
AB  - Normal and schizophrenic Ss (N=24 each) did pursuit rotor tracking and
      reminiscence was the score of interest; rest pauses of 2, 12, and 30 min., and 1,
      6, and 24 hr. were interpolated in counterbalanced order after 5 min. of
      practice. It was predicted, on the basis of previous work, that schizophrenics
      would show greater reminiscence after the longer rest pauses, normals after the
      shorter rest pauses. The expected cross-over effect was found, but at a non
      significant level only. There were no order effects. A discussion is given of the
      relation of these results to the interpretation of schizophrenia in terms of
      ''arousal." 

PMID- 23952663
TI  - Effects of local muscular fatigue due to isotonic and isometric exercise upon
      fractionated reaction time components.
AB  - Fractionated RT for a right knee-extension task was assessed on eight male and
      eight female Ss over eight treatment days. Following four consecutive days of 75
      RT trials /day to insure stabilized strength and RT components, Ss were
      administered two days of bench stepping and two days of isometric exercise
      designed to induce muscular fatigue of the knee extensors. Significant strength
      decrements of up to 24% were induced by both the isotonic (bench stepping) and
      isometric exercise treatment conditions but no changes were observed in
      fractionated RT components. The results would seem to indicate that performance
      differences in fine-versus gross-motor skill tasks due to fatigue need to be more
      carefully examined. 

PMID- 23952664
TI  - Response complexity and the latency of different movement patterns.
AB  - Two series of experiments are described in which RT of responses of varying
      complexity is investigated. Complexity of arm movements was manipulated in terms
      of (a) the amount of force exerted in resisted movements, (b) the distance moved
      by the limb and the direction of movement, using reversing or continuing
      movements, and (c) the combining of the arms in reversing and continuing
      movements. Simple and two-choice RT situations were used. As response complexity
      increased in terms of the number of sets of response units that have to be
      organized into a spatio-temporal sequence, the latency correspondingly increased.
      However latency was not affected by changes in the amount of force exerted, or in
      simple reversal movements. The implications of these results are discussed. 

PMID- 23952665
TI  - Anticipatory rehearsal in inverted-reversed printing.
AB  - Continuous practice printing upside down and backward letters of the alphabet was
      given for 4 min. followed by a 2-min. rest, and then a final 2 min. of practice.
      Half the Ss had prior information of the letter with which they were to start
      printing and half did not; half the Ss printed with the right hand and half with
      the left; and Ss were composed of 48 male and 48 female dextrals. The factorial
      combination of these three variables during the prerest period yielded a 2 * 2 *
      2 factorial design (N = 12/cell). During the postrest period the same variables
      were manipulated, but Ss who had been given prior information were uninformed,
      and vice versa. The initial negative slope of the performance curve was found
      only with Informed male Ss during prerest practice, but all groups produced an
      initial drop in the postrest performance curve. It was concluded that different
      processes determine the shape of the prerest and postrest curves. 

PMID- 23952666
TI  - Influence of induced muscular tension on a time-estimation motor task.
AB  - Right-handed female volunteers (N=28) participated in a study examining the
      inverted-U relationship between activation, as altered by various levels of
      induced muscular tension, and behavioral efficiency. Heart rate and skin
      resistance were used as measures of activation. A time-estimation task required
      moving a handle with the right hand across a 60-cm. track in 2 sec. while
      exerting tension (either 0, 25, 50, or 75% of maximum grip strength) with the
      left hand on stabilized hand dynamometer. There was no statistical support for
      the inverted U theory, but the mean performance scores indicated a trend toward
      the inverted U, with the most accurate mean performance occurring at the 50%
      induced tension level. 

PMID- 23952667
TI  - Effect of need achievement and task difficulty on competitive and noncompetitive
      motor performance.
AB  - Atkinson's theory of achievement motivation was tested on a stabliometer task of
      either low, moderate, or high task difficulty. Ss (N=120) were either assigned to
      a condition with competition for a monetary reward or to a noncompetitive no
      reward condition. In the high task-difficulty condition Ss competing for a reward
      performed better on initial trails than did Ss in the noncompetitive condition.
      Although no performance differences were found between Ss who tended to achieve
      success and Ss who tended to avoid failure, the latter Ss had poorer consistency
      of performance (intravariance scores) on initial learning trials. 

PMID- 23952668
TI  - Therapeutic effects of CuII(atsm) in the SOD1-G37R mouse model of amyotrophic
      lateral sclerosis.
AB  - Our objective was to assess the copper(II) complex of diacetylbis(4
      methylthiosemicarbazone) [Cu(II)(atsm)] for its preclinical potential as a novel
      therapeutic for ALS. Experimental paradigms used were designed to assess
      Cu(II)(atsm) efficacy relative to treatment with riluzole, as a function of dose
      administered, and when administered post symptom onset. Mice expressing human
      Cu/Zn superoxide dismutase harbouring the disease-causing G37R mutation (SOD1
      G37R) were used and effects of Cu(II)(atsm) determined by assessing mouse
      survival and locomotor function (rotarod assay). Cu(II)(atsm) improved SOD1-G37R
      mouse survival and locomotor function in a dose-dependent manner. The highest
      dose tested improved survival by 26%. Riluzole had a modest effect on mouse
      survival (3.3%) but it did not improve locomotor function. Cotreatment with
      Cu(II)(atsm) did not alter the protective activity of Cu(II)(atsm) administered
      on its own. Commencing treatment with Cu(II)(atsm) after the onset of symptoms
      was less effective than treatments that commenced before symptom onset but still
      significantly improved locomotor function and survival. Improved locomotor
      function and survival of SOD1-G37R mice supports the potential for Cu(II)(atsm)
      as a novel treatment option for ALS.

PMID- 23952672
TI  - CO oxidation on supported single Pt atoms: experimental and ab initio density
      functional studies of CO interaction with Pt atom on theta-Al2O3(010) surface.
AB  - Although there are only a few known examples of supported single-atom catalysts,
      they are unique because they bridge the gap between homogeneous and heterogeneous
      catalysis. Here, we report the CO oxidation activity of monodisperse single Pt
      atoms supported on an inert substrate, theta-alumina (Al2O3), in the presence of
      stoichiometric oxygen. Since CO oxidation on single Pt atoms cannot occur via a
      conventional Langmuir-Hinshelwood scheme (L-H scheme) which requires at least one
      Pt-Pt bond, we carried out a first-principles density functional theoretical
      study of a proposed pathway which is a variation on the conventional L-H scheme
      and inspired by the organometallic chemistry of platinum. We find that a single
      supported Pt atom prefers to bond to O2 over CO. CO then bonds with the
      oxygenated Pt atom and forms a carbonate which dissociates to liberate CO2,
      leaving an oxygen atom on Pt. Subsequent reaction with another CO molecule
      regenerates the single-atom catalyst. The energetics of the proposed mechanism
      suggests that the single Pt atoms will get covered with CO3 unless the
      temperature is raised to eliminate CO2. We find evidence for CO3 coverage at room
      temperature supporting the proposed mechanism in an in situ diffuse reflectance
      infrared study of CO adsorption on the catalyst's supported single atoms. Thus,
      our results clearly show that supported Pt single atoms are catalytically active
      and that this catalytic activity can occur without involving the substrate.
      Characterization by electron microscopy and X-ray absorption studies of the
      monodisperse Pt/theta-Al2O3 are also presented. 

PMID- 23952673
TI  - Wetting on physically patterned solid surfaces: the relevance of molecular
      dynamics simulations to macroscopic systems.
AB  - We used molecular dynamics (MD) simulations to study the wetting of Lennard-Jones
      cylindrical droplets on surfaces patterned with grooves. By scaling the surface
      topography parameters with the droplet size, we find that the preferred wetting
      modes and contact angles become independent of the droplet size. This result is
      in agreement with a mathematical model for the droplet free energy at small Bond
      numbers for which the effects of gravity are negligible. The MD contact angles
      for various wetting modes are in good agreement with those predicted by the
      mathematical model. We construct phase diagrams of the dependence of the wetting
      modes observed in the MD simulations on the topography of the surface. Depending
      on the topographical parameters characterizing the surface, multiple wetting
      modes can be observed, as is also seen experimentally. Thus, our studies indicate
      that MD simulations can yield insight into the large-length-scale behavior of
      droplets on patterned surfaces. 

PMID- 23952674
TI  - Incubation of selected fermentable fibres with feline faecal inoculum:
      correlations between in vitro fermentation characteristics and end products.
AB  - This study aimed to evaluate correlations between fermentation characteristics
      and end products of selected fermentable fibres (three types of fructans, citrus
      pectin, guar gum), incubated with faecal inocula from donor cats fed two diets,
      differing in fibre and protein sources and concentrations. Cumulative gas
      production was measured over 72 h, fermentation end products were analysed at 4,
      8, 12, 24, 48 and 72 h post-incubation, and quantification of lactobacilli,
      bifidobacteria and bacteroides in fermentation liquids were performed at 4 and 48
      h of incubation. Partial Pearson correlations, corrected for inoculum, were
      calculated to assess the interdependency of the fermentation characteristics of
      the soluble fibre substrates. Butyric and valeric acid concentrations increased
      with higher fermentation rates, whereas acetic acid declined. Concentrations of
      butyric acid (highest in fructans) and propionic acid were inversely correlated
      with protein fermentation end products at several time points, whereas
      concentrations of acetic acid (highest in citrus pectin) were positively
      correlated with these products at most time points. Remarkably, a lack of clear
      relationship between the counts of bacterial groups and their typically
      associated products after 4 h of incubation was observed. Data from this
      experiment suggest that differences in fibre fermentation rate in feline faecal
      inocula coincide with typical changes in the profile of bacterial fermentation
      products. The observed higher concentrations of propionic and butyric acid as a
      result of fibre fermentation could possibly have beneficial effects on intestinal
      health, and may be confounded with a concurrent decrease in the production of
      putrefactive compounds. In conclusion, supplementing guar gum or fructans to a
      feline diet might be more advantageous compared with citrus pectin. However, in
      vivo research is warranted to confirm these conclusions in domestic cats. 

PMID- 23952675
TI  - Starch synthase 4 is essential for coordination of starch granule formation with
      chloroplast division during Arabidopsis leaf expansion.
AB  - Arabidopsis thaliana mutants lacking the SS4 isoform of starch synthase have
      strongly reduced numbers of starch granules per chloroplast, suggesting that SS4
      is necessary for the normal generation of starch granules. To establish whether
      it plays a direct role in this process, we investigated the circumstances in
      which granules are formed in ss4 mutants. Starch granule numbers and distribution
      and the accumulation of starch synthase substrates and products were investigated
      during ss4 leaf development, and in ss4 mutants carrying mutations or transgenes
      that affect starch turnover or chloroplast volume. We found that immature ss4
      leaves have no starch granules, but accumulate high concentrations of the starch
      synthase substrate ADPglucose. Granule numbers are partially restored by
      elevating the capacity for glucan synthesis (via expression of bacterial glycogen
      synthase) or by increasing the volumes of individual chloroplasts (via
      introduction of arc mutations). However, these granules are abnormal in
      distribution, size and shape. SS4 is an essential component of a mechanism that
      coordinates granule formation with chloroplast division during leaf expansion and
      determines the abundance and the flattened, discoid shape of leaf starch
      granules. 

PMID- 23952677
TI  - An alternative method in fixation of tibial transverse fractures by intramedullar
      nailing: biomechanical and histopathologic investigation.
AB  - A new method was used in fixation of tibial bone fractures. Intramadular nailing
      (IMN) has been used into mid-diaphysis on left tibias of New Zeland rabbits (n =
      5) via an in vivo work. To enable fixation of fracture, without causing too much
      screw damage on bone and avoiding malunion, nano- and micro-scale hydroxyapatite
      (HA) was coated at two ends (25 mm in length) of intramadular nails before
      implantation. After six weeks of survival period and sacrifizing, biomechanical
      tests and histopathologic examinations were executed. Such experiments have
      revealed that good stabilization and hence better fracture union for both treated
      IMN groups (NHA and MHA) over the standard IMN'. Pull-out tests showed the
      tensile strengths obtained to be significantly higher for the nano (NHA) and
      micro scale-MHA coated IMN compared to the uncoated standard IM nailing. 

PMID- 23952678
TI  - Disruption of the electrical conductivity of highly conductive poly(3,4
      ethylenedioxythiophene):poly(styrene sulfonate) by hypochlorite.
AB  - The effect of hypochlorite treatment on the layer thickness and conductivity of a
      state-of-the-art high conducting poly(3,4-ethylenedioxythiophene):poly(styrene
      sulfonate) (PEDOT:PSS) is investigated as a function of exposure time and
      hypochlorite concentration. Because of overoxidation by the hypochlorite the
      PEDOT:PSS conductivity is decreased by 10 orders of magnitude. Comparison of
      thickness and conductivity as a function of time shows that a residual insulating
      layer remains on the substrate upon treatment. Going from a low (<0.01%) to a
      high (>0.1%) hypochlorite concentration the interaction between PEDOT:PSS and
      hypochlorite changes from reaction- to diffusion limited. The decrease in
      conductivity can be interpreted in terms of the interruption of percolating
      conductive pathways by the reaction between PEDOT and hypochlorite. 

PMID- 23952676
TI  - Lepidium sativum but not Nigella sativa affects carbamazepine disposition in an
      animal model.
AB  - Efficacy and safety profile of a drug may be affected when concomitantly used
      with herbal medicines. The present study was conducted to investigate the effects
      of some commonly used herbal products viz. Nigella sativa (Black seed) and
      Lepidium sativum (Garden cress) on the pharmacokinetics of carbamazepine (CBZ), a
      narrow therapeutic index drug, in an animal model. In a control group, five
      rabbits received 40 mg/kg of CBZ orally and blood samples were withdrawn at
      different time intervals (0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hrs) from a
      marginal ear vein. After a suitable washout period, an aqueous saline suspension
      of Nigella sativa (200 mg/kg) or Lepidium sativum (150 mg/kg) was given orally
      for eight days to the rabbits. On day eight, CBZ (40 mg/kg) was re-administrated
      orally and blood samples were collected using the same sampling scheme. Drug
      levels in plasma were determined by liquid chromatography and pharmacokinetic
      parameters were calculated using non-compartmental analysis. No significant
      difference was observed in the maximum concentration (Cmax), area under
      concentration curve (AUC), half-life (T1/2), clearance (Cl/F) and volume of
      distribution (Vz/F) of CBZ following Nigella sativa treatment. Whereas, increased
      Cmax, absorption rate measured by the time to Cmax (Tmax), and prolongation of
      the terminal elimination half-life (T1/2) were observed after the co
      administration with Lepidium sativum. Findings of the present study suggest that
      concurrent use of Lepidium sativum alters the pharmacokinetics of CBZ in an
      animal model. Further confirmation of these results in humans will warrant
      changes in CBZ dose and/or frequency before co-administration with these herbal
      medicines. 

PMID- 23952679
TI  - Facets of the childhood anxiety sensitivity index among Serbian youth.
AB  - Data from factor analytic studies using the Child Anxiety Sensitivity Index
      (CASI) suggest that global anxiety sensitivity (AS) is best represented by three
      or four underlying factors or facets. The aim of this study was to identify
      facets best representing the CASI structure in its Serbian version. Confirmatory
      factor analysis was used on data collected from 456 non-referred children in
      Serbia. A 13-item version of the CASI provided a better fit to the data than the
      original 18-item version. The four-factor model of the CASI-13 with disease,
      unsteady, mental incapacitation, and social concerns facets provided the best
      fits for the data and it was found to be fully invariant (configural, metric, and
      scalar invariance) across gender and age. Among Serbian children, hierarchical
      structure was found for a 13-item CASI version with a single higher-order factor
      of global AS represented by four underlying facets. Future research will consider
      these AS facets and their role in the development, maintenance, and exacerbation
      of anxiety symptoms in children. 

PMID- 23952680
TI  - Sequential injection approach for simultaneous determination of ultratrace
      plutonium and neptunium in urine with accelerator mass spectrometry.
AB  - An analytical method was developed for simultaneous determination of ultratrace
      level plutonium (Pu) and neptunium (Np) using iron hydroxide coprecipitation in
      combination with automated sequential injection extraction chromatography
      separation and accelerator mass spectrometry (AMS) measurement. Several
      experimental parameters affecting the analytical performance were investigated
      and compared including sample preboiling operation, aging time, amount of
      coprecipitating reagent, reagent for pH adjustment, sedimentation time, and
      organic matter decomposition approach. The overall analytical results show that
      preboiling and aging are important for obtaining high chemical yields for both Pu
      and Np, which is possibly related to the aggregation and adsorption behavior of
      organic substances contained in urine. Although the optimal condition for Np and
      Pu simultaneous determination requires 5-day aging time, an immediate
      coprecipitation without preboiling and aging could also provide fairly
      satisfactory chemical yields for both Np and Pu (50-60%) with high sample
      throughput (4 h/sample). Within the developed method, (242)Pu was exploited as
      chemical yield tracer for both Pu and Np isotopes. (242)Pu was also used as a
      spike in the AMS measurement for quantification of (239)Pu and (237)Np
      concentrations. The results show that, under the optimal experimental condition,
      the chemical yields of (237)Np and (242)Pu are nearly identical, indicating the
      high feasibility of (242)Pu as a nonisotopic tracer for (237)Np determination in
      real urine samples. The analytical method was validated by analysis of a number
      of urine samples spiked with different levels of (237)Np and (239)Pu. The
      measured values of (237)Np and (239)Pu by AMS exhibit good agreement (R(2) >=
      0.955) with the spiked ones confirming the reliability of the proposed method. 

PMID- 23952681
TI  - Relative prevalence of Mycobacterium marinum in fish collected from aquaria and
      natural freshwaters in central Europe.
AB  - A survey was carried out on occurrence of Mycobacterium marinum in fish kept in
      aquaria and those living in their natural environment. Species-specific qPCR
      targeting the erp and IS2404 genes together with the conventional culture method
      were used. The analysis of 72 ornamental fish (n = 216 samples: gills, muscle and
      intestine) collected from aquaria revealed the presence of M. marinum in 30
      individuals (41.7%) of whom 17 (23.6%) were later culture positive. Culture
      independent detection revealed the presence of M. marinum in 16 of 83
      environmental samples (19.3%) collected in aquaria. The presence of viable M.
      marinum cells was later confirmed in 5 samples (6.0%). No qPCR or culture
      positivity was observed when 123 groundwater fish and their corresponding
      environmental samples (n = 142) were analysed.

PMID- 23952682
TI  - The effect of low-level laser therapy on the healing of hard palate mucosa and
      the oxidative stress status of rats.
AB  - OBJECTIVE: The biostimulation effects of low-level laser therapy (LLLT) have been
      demonstrated recently. This study investigated the effects of LLLT on palatal
      mucoperiosteal wound healing and oxidative stress status in rats. MATERIAL AND
      METHOD: Forty-two male Wistar rats weighing 250-300 g were used in this study. A
      standardized full-thickness wound was created in the mucoperiosteum of the hard
      palates of the rats using a 3-mm-diameter biopsy punch. Treatment using a GaAlAs
      laser at a wavelength of 940 nm and a dose of 10 J/cm(2) was initiated after
      surgery and repeated on the 2nd, 4th, and 6th days post-surgery. Seven animals
      from each group were sacrificed on the 7th, 14th, and 21st days after surgery.
      Total antioxidant status and total oxidative status were measured in serum.
      RESULTS: The histopathological findings revealed reduced numbers of inflammatory
      cells on the 7th day, increased mitotic activity of fibroblasts on the 14th and
      21st day, and the same degree of collagen synthesis and vascularization on the
      days 7, 14, and 21 in the LLLT group compared with the control group. No
      significant differences in total oxidative status and total antioxidant status
      were observed between the groups. CONCLUSION: LLLT using a GaAlAs laser at a
      wavelength of 940 nm and a dose of 10 J/cm(2) elicited a positive healing effect
      on palatal mucoperiosteal wounds likely via the induction of fibroblasts. The
      oxidative stress status was not affected by LLLT.

PMID- 23952683
TI  - Insight into crizotinib resistance mechanisms caused by three mutations in ALK
      tyrosine kinase using free energy calculation approaches.
AB  - As a safe and efficacious drug, crizotinib was approved by the U.S. Food and Drug
      Administration (FDA) in 2011 for the treatment of advanced fusion-type nonsmall
      cell lung cancer. Although high response ratio was detected from the patients
      treated with crizotinib, the cancer has eventually conferred resistance to
      crizotinib. Several drug resistance mutations have been found in the anaplastic
      lymphoma kinase (ALK) tyrosine kinase domain as the target for crizotinib, but
      the drug resistance mechanisms remain unclear. Therefore, in this study, the
      adaptive biasing force (ABF) method and two-end-state free energy calculation
      approaches were employed to elucidate the resistance mechanisms of crizotinib
      induced by the mutations L1152R, G1202R, and S1206Y. The ABF simulation results
      suggest that the reaction coordinates for the unbinding processes of crizotinib
      from the binding pockets of the mutated ALKs is different from that of the wild
      type ALK. The potentials of mean force for the crizotinib unbinding and the
      binding free energies predicted by the two-end-state free energy calculations are
      consistent with the experimental data. Our results indicate that the three
      mutations weaken the binding affinity of crizotinib obviously and lead to drug
      resistance. The free energy decomposition analysis illustrates the importance of
      the loss of two important H-bonds in the L1152R and S1206Y mutants on drug
      resistance. The entropy analysis shows that the entropy term plays a critical
      role in the substantial change of the conformational entropies of G1202R and
      L1152R. Our results reveal the mechanisms of drug resistance and provide vital
      clues for the development of new inhibitors to combat drug resistance. 

PMID- 23952684
TI  - Comparison of a safety strategy using transradial access and dual-axis rotational
      coronary angiography with transfemoral access and standard coronary angiography.
AB  - OBJECTIVES: We sought to investigate the radiation exposure and contrast
      utilization associated with using a strategy of transradial access and rotational
      angiography (radial-DARCA) compared to the traditional approach of transfemoral
      access and standard angiography (femoral-SA). BACKGROUND: There is an increased
      focus on optimizing patient safety during cardiac catheterization procedures.
      Professional guidelines have highlighted physician responsibility to minimize
      radiation doses and contrast volume. Dual axis rotational coronary angiography
      (DARCA) is the most recently investigated type of rotational angiography. This
      new technique permits complete visualization of the left or right coronary tree
      with a single injection, and is felt to reduce contrast and radiation exposure.
      METHODS: A total of 56 consecutive patients who underwent radial-DARCA were
      identified. From the same time period, an age- and gender-matched group of 61
      patients who had femoral-SA were selected for comparison. Total volume of
      contrast agent used, fluoroscopy time, and 2 measures of radiation dose (dose
      area product and air kerma) were recorded for each group. RESULTS: Mean contrast
      agent use and patient radiation exposure of the radial-DARCA group were
      significantly less than that of the femoral-SA group. There was no significant
      difference in fluoroscopy time between the 2 groups. CONCLUSIONS: Physicians can
      successfully employ an innovative safety strategy of transradial access combined
      with DARCA that is feasible and is associated with lower radiation doses and
      contrast volume than femoral artery access and traditional coronary angiography
      approach.

PMID- 23952685
TI  - Integrating models and data to estimate the structural reliability of utility
      poles during hurricanes.
AB  - Utility systems such as power and communication systems regularly experience
      significant damage and loss of service during hurricanes. A primary damage mode
      for these systems is failure of wooden utility poles that support conductors and
      communication lines. In this article, we present an approach for combining
      structural reliability models for utility poles with observed data on pole
      performance during past hurricanes. This approach, based on Bayesian updating,
      starts from an imperfect but informative prior and updates this prior with
      observed performance data. We consider flexural and foundation failure mechanisms
      in the prior, acknowledging that these are an incomplete, but still informative,
      subset of the possible failure mechanisms for utility poles during hurricanes. We
      show how a model-based prior can be updated with observed failure data, using
      pole failure data from Hurricane Katrina as a case study. The results of this
      integration of model-based estimates and observed performance data then offer a
      more informative starting point for power system performance estimation for
      hurricane conditions. 

PMID- 23952686
TI  - AtMBP-1, an alternative translation product of LOS2, affects abscisic acid
      responses and is modulated by the E3 ubiquitin ligase AtSAP5.
AB  - The LOS2 gene in Arabidopsis encodes an enolase with 72% amino acid sequence
      identity with human ENO1. In mammalian cells, the alpha-enolase (ENO1) gene
      encodes both a 48 kDa glycolytic enzyme and a 37 kDa transcriptional suppressor
      protein that are targeted to different cellular compartments. The tumor
      suppressor c-myc binding protein (MBP-1), which is alternatively translated from
      the second start codon of ENO1 transcripts, is preferentially localized in nuclei
      while alpha-enolase is found in the cytoplasm. We report here that an Arabidopsis
      MBP-1-like protein (AtMBP-1) is alternatively translated from full-length LOS2
      transcripts using a second start codon. Like mammalian MBP-1, this truncated form
      of LOS2 has little, if any, enolase activity, indicating that an intact N
      terminal region of LOS2 is critical for catalysis. AtMBP-1 has a short half-life
      in vivo and is stabilized by the proteasome inhibitor MG132, indicating that it
      is degraded via the ubiquitin-dependent proteasome pathway. Arabidopsis plants
      that over-express AtMBP-1 are hypersensitive to abscisic acid (ABA) during seed
      germination and show defects in vegetative growth and lateral stem development.
      AtMBP-1 interacts directly with the E3 ubiquitin ligase AtSAP5 and co-expression
      of these proteins resulted in destabilization of AtMBP-1 in vivo and abolished
      the developmental defects associated with AtMBP-1 over-expression. Thus, AtMBP-1
      is as a bona fide alternative translation product of LOS2. Accumulation of this
      factor is limited by ubiquitin-dependent destabilization, apparently mediated by
      AtSAP5.

PMID- 23952687
TI  - Melatonin synergizes with low doses of L-DOPA to improve dendritic spine density
      in the mouse striatum in experimental Parkinsonism.
AB  - The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), is the preferred
      drug for Parkinson's disease, but long-term treatment results in the drug-induced
      dyskinesias and other side effects. This study was undertaken to examine whether
      melatonin could potentiate low dose L-DOPA effects in 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-induced experimental parkinsonism. Mice were treated
      with the parkinsonian neurotoxin, MPTP, and different doses of melatonin and low
      doses of L-DOPA. Behavior, striatal histology, and dopamine metabolism were
      evaluated on the 7th day. MPTP-induced striatal dopamine loss was not modified by
      melatonin administration (10-30 mg/kg; i.p. at 10-hr intervals, 6 times; or at 2
      hr intervals, by day). However, low doses of L-DOPA (5 mg/kg, by oral gavage)
      administered alone or along with melatonin (10 mg/kg, i.p.) twice everyday for 2
      days, 10 hr apart, after two doses of MPTP significantly attenuated striatal
      dopamine loss and provided improvements in both catalepsy and akinesia.
      Additionally, Golgi-impregnated striatal sections showed preservation of the
      medium spiny neurons, which have been damaged in MPTP-treated mouse. The results
      demonstrated that melatonin, but not L-DOPA, restored spine density and spine
      morphology of medium spiny neurons in the striatum and suggest that melatonin
      could be an ideal adjuvant to L-DOPA therapy in Parkinson's disease, and by the
      use of this neurohormone, it is possible to bring down the therapeutic doses of L
      DOPA. 

PMID- 23952688
TI  - Intraventricular and lumbar intrathecal administration of antibiotics in
      postneurosurgical patients with meningitis and/or ventriculitis in a serious
      clinical state.
AB  - OBJECT: To date, reports on the clinical efficacy of intraventricularly and
      intrathecally administered antibiotics for the treatment of neurosurgical
      ventriculitis and meningitis in adults are limited. The authors aimed to evaluate
      the efficacy and safety of the intraventricular (IVT) and lumbar intrathecal (IT)
      administration of antibiotics in critically ill neurosurgical patients. METHODS:
      Thirty-four postneurosurgical patients with meningitis and ventriculitis were
      studied. Intraventricular/lumbar intrathecal antibiotics were administered due to
      positive CSF cultures persisting despite the use of intravenous antibiotics. The
      time period until CSF sterilization, changes in clinical state, and efficacy of
      different routes of antibiotic administration were evaluated. RESULTS: The mean
      time necessary to obtain CSF sterilization was 2.9 +/- 2.7 days (range 1-12
      days). The CSF cultures became negative within 24 hours after the administration
      of IVT/IT antibiotics in 17 patients (50%) and up to 48 hours in a further 6
      patients (18%). The clinical outcome of patients assessed by the modified Rankin
      Scale improved in 17 patients (50%), stayed unchanged in 10 patients (29%), and
      was impaired in 1 patient (3%). Six patients (18%) died; however, 2 of them died
      due to reasons not directly related to meningitis or ventriculitis, so the
      overall mortality rate for meningitis and/or ventriculitis was 11.8% in this
      group of patients. All patients with ventriculitis (n = 4) were treated by
      antibiotics administered via the IVT route. The average time to CSF sterilization
      was 6.5 days in the patients with ventriculitis. Thirty patients had clinical
      signs of meningitis without ventriculitis. Despite the higher ratio of
      unfavorable Gram-negative meningitis in the subgroup of patients treated via
      lumbar drainage, the mean duration of CSF sterilization was 2.2 days compared
      with 2.6 days in the subgroup treated via external ventricular drainage, a
      difference that was not statistically significant (p = 0.3). Adverse effects of
      IVT/IT antibiotics appeared in 3 of 34 patients and were of low clinical
      significance. CONCLUSIONS: Intraventricular/lumbar intrathecal antibiotics can
      lead to very quick CSF sterilization in postneurosurgical patients with
      meningitis and ventriculitis. The relapse rate of meningitis and/or ventriculitis
      is also very low among patients treated by IVT/IT antibiotics.
      Intraventricular/lumbar intrathecal administration of antibiotics appears to be
      an effective and safe treatment for infections of the CNS caused by multidrug
      resistant organisms. In patients with signs of ventriculitis, the authors prefer
      the IVT route of antibiotics. This study did not prove a lower efficacy of
      administration of antibiotics via lumbar drainage compared with the ventricular
      route in patients with meningitis.

PMID- 23952689
TI  - Testing the effects of an empowerment-based leadership development programme:
      part 2 - staff outcomes.
AB  - AIM: To determine if nurse leaders' attendance at a leadership development
      programme based on an empowerment framework would increase staff perceptions of
      organisational support and organisational commitment. BACKGROUND: Leadership
      empowering behaviours are teachable relational competencies that have been
      associated with quality leader-staff relationships and positive staff outcomes.
      METHODS: A quasi-experimental, pre-test-post-test design was used to compare
      perceptions of staff whose leaders participated in a year-long leadership
      programme with staff of similar leaders who did not attend the programme. A
      series of multiple regression analyses were used to test the conceptual model of
      programme effects. RESULTS: Leaders' programme participation was directly
      associated with greater staff organisational commitment 1 year after the
      programme. Both programme attendance and leader-empowering behaviours were found
      to act as independent catalysts for staff empowerment, with structural
      empowerment partially mediating the effects of leader empowering behaviours on
      organisational commitment. CONCLUSIONS: Leader participation in a development
      programme based on an empowerment framework may be an important means of
      increasing staff organisational commitment, a key predictor of staff turnover.
      IMPLICATIONS FOR NURSE MANAGEMENT: Leadership development programmes should
      emphasize relational competencies, including leader empowering behaviours, given
      their potential for enhancing organisational commitment.

PMID- 23952690
TI  - Hymenolepis diminuta infections in tenebrionid beetles as a model system for
      ecological interactions between helminth parasites and terrestrial intermediate
      hosts: a review and meta-analysis.
AB  - The cestode Hymenolepis diminuta (Cyclophyllidea) uses a variety of insects as
      its intermediate host, where ingestion of eggs results in development in the
      hemocoel of a cysticercoid that is infective to a rat definitive host. Species in
      2 genera, Tenebrio and Tribolium (Coleoptera: Tenebrionidae) have been used
      extensively as laboratory intermediate hosts. This review examines experimental
      studies on ecological aspects of the relationship between H. diminuta and
      tenebrionid beetles, including the acquisition and establishment of the parasite,
      host effects on the parasite, and parasite effects on the host. A meta-analysis
      of infection results from the literature revealed strong relationships across
      host species and strains between (1) prevalence and intensity of infection, (2)
      efficiency of cysticercoid production and exposure conditions, and (3) variance
      in abundance or intensity of infection relative to their respective means. The
      underlying mechanisms producing these patterns remain elusive. Comparative
      studies are infrequent, and the use of divergent methodologies hampers
      comparisons among studies. In spite of these problems, there is much to recommend
      this as a terrestrial host-parasite model system. It represents those
      relationships in which mostly minor, but occasionally major, responses to
      parasitic infection occur, and in which host genetics and environmental
      conditions can serve as modifying factors. Moreover, this is a tractable
      experimental system, and is backed by an extensive literature on host biology.

PMID- 23952691
TI  - When less is more--microRNAs and psychiatric disorders.
AB  - OBJECTIVE: MicroRNAs are small non-coding RNA molecules that regulate gene
      expression, including genes involved in neuronal function and plasticity that
      have relevance for brain function and mental health. We therefore performed a
      systematic review of miRNAs in general adult psychiatric disorders. METHOD:
      Systematic searches in PubMed/MEDLINE and Web of Science were conducted to
      identify published clinical articles on microRNAs in general adult psychiatric
      disorders. We also reviewed references from included articles. RESULTS: There is
      mounting evidence of microRNAs' regulatory roles in a number of central nervous
      system processes, including neurogenesis and synaptic plasticity. The majority of
      clinical studies of microRNAs in psychiatric disorders are in schizophrenia,
      where a number of specific microRNAs have been identified in separate studies.
      There is some evidence of marked downregulation of some microRNAs in affective
      disorders. Treatment with antidepressants appears to upregulate microRNA levels.
      There is currently little evidence from human studies in anxiety, addiction or
      other psychiatric disorders. CONCLUSION: MicroRNA research in psychiatry is
      currently in a nascent period, but represents an emerging and exciting area, with
      the potential to clarify molecular mechanisms of disease and identify novel
      biomarkers and therapeutic agents.

PMID- 23952692
TI  - The polymorphisms of osteopontin gene and plasma osteopontin protein levels with
      susceptibility to colorectal carcinoma.
AB  - Osteopontin (OPN) plays an important role in the development and progression of
      some tumors. The polymorphisms of OPN probably change its expression and
      contribute to interindividual differences of susceptibility to some cancers. The
      purpose of the present study was to explore the association of rs9138 (+1239;
      3'UTR: 3'untranslated regions) and rs1126616 (+750; exon 7) polymorphisms located
      in the OPN gene with colorectal carcinoma (CRC) susceptibility and to investigate
      the correlation of the polymorphisms, plasma levels of the OPN protein,
      clinicopathologic parameters, tumor markers, and lipid. The genotypes were
      determined by polymerase chain reaction-restriction fragment length polymorphism.
      The plasma levels, tumor markers, and lipid were measured by enzyme-linked
      immunosorbent assay. The results indicated that genotype AA and AC of rs9138 and
      CC and CT of rs1126616 were associated with increased risk of CRC. The allelic
      frequencies of rs9138A, rs1126616C, and the haplotype (A-C) were associated with
      increased risk of CRC. Although there was no significant difference of plasma
      levels in various genotypes, increased plasma protein expression in CRC patients
      compared with controls was found. Our results suggested that the rs9138 and
      rs1126616 of OPN were associated with CRC risk, and the OPN protein in plasma may
      be a potential tumor marker of CRC. 

PMID- 23952693
TI  - Gross anatomy of the brachial plexus in the giant Anteater (Myrmecophaga
      tridactyla).
AB  - Ten forelimbs of five Myrmecophaga tridactyla were examined to study the anatomy
      of the brachial plexus. The brachial plexuses of the M. tridactyla observed in
      the present study were formed by the ventral rami of the last four cervical
      spinal nerves, C5 through C8, and the first thoracic spinal nerve, T1. These
      primary roots joined to form two trunks: a cranial trunk comprising ventral rami
      from C5-C7 and a caudal trunk receiving ventral rami from C8-T1. The nerves
      originated from these trunks and their most constant arrangement were as follows:
      suprascapular (C5-C7), subscapular (C5-C7), cranial pectoral (C5-C8), caudal
      pectoral (C8-T1), axillary (C5-C7), musculocutaneous (C5-C7), radial (C5-T1),
      median (C5-T1), ulnar (C5-T1), thoracodorsal (C5-C8), lateral thoracic (C7-T1)
      and long thoracic (C6-C7). In general, the brachial plexus in the M. tridactyla
      is similar to the plexuses in mammals, but the number of rami contributing to the
      formation of each nerve in the M. tridactyla was found to be larger than those of
      most mammals. This feature may be related to the very distinctive anatomical
      specializations of the forelimb of the anteaters. 

PMID- 23952694
TI  - Steadiness as a function of prior exercise.
AB  - The effect of exercise on arm and hand steadiness was studied in two experiments.
      Unsteadiness following exercise was 35, 53, and 181% greater than pre-pedaling
      performance for the treatments in which heart rate (HR) was raised to 100, 130,
      and 160 bpm respectively. The recovery pattern of steadiness following 6 min. of
      cycling exercise (mean HR 169 bpm) was measured; immediately following the
      exercise unsteadiness was 143% greater than during pre-pedaling performance and
      decreased as more time elapsed between the exercise and the steadiness task. When
      measured 240 sec. after the exercise, unsteadiness was still 28% greater than in
      pre-exercise performance. Steadiness is markedly affected by preliminary exercise
      which raises the activation level, with unsteadiness being greatest at the
      highest levels of activation. 

PMID- 23952695
TI  - Effector system mechanisms of coordination.
AB  - Current interest in motor learning has prompted researchers to develop models
      that explain the events or mechanisms underlying skill acquisition. For the most
      part these models have focused on sensory and perceptual mechanisms. This
      commentary presents a theoretical explanation of effector system mechanisms of
      coordination. Options are available in the central control centers and their
      peripheral components, tonic and phasic motor units. Implications for the
      methodology of motor learning are discussed as they relate to a paramount factor
      responsible for prompting individuals to select the most efficacious effector
      system mechanism option. 

PMID- 23952696
TI  - Motor response recognition.
AB  - Two experiments tested the hypothesis that estimation of response outcome
      involves the independent processes of evaluating response-produced feedback
      stimuli and associating a label from an interval scale to these stimuli. Ss
      practiced a linear positioning movement to a stop before estimating the movement
      distance either in in. or mm. and reproducing the movement in a single criterion
      test trial. The results supported the hypothesis. There was no difference between
      groups in movement error, while estimation errors for both groups were
      significantly greater than their respective movement errors. The smaller
      estimation error in the in. group suggested that attaching a label to the
      response-produced feedback is itself a learned phenomenon. 

PMID- 23952697
TI  - Dynamic visual acuity and performance in a catching task.
AB  - Each of 30 Ss was given tests of dynamic and static visual acuity and then
      participated in a ball-catching task. Performance in the latter task was an
      inverted U-shaped function of duration of the occluded period, the time between
      the termination of the 80-msec. viewing period and the estimated onset of the
      "latency period" (the point in time at which the ball could no longer serve to
      cue Ss response). Dynamic and static visual acuity scores were not significantly
      correlated but, with static visual acuity partialled out, dynamic visual acuity
      and catching performance were significantly correlated. 

PMID- 23952698
TI  - Effects of fulcrum height on stabilometer performance.
AB  - This study investigated the relationship between time on balance and number of
      errors in stabilometer performance, with height of the fulcrum as an independent
      variable. Ss were 2 groups of 25 female undergraduates. One group was given 10
      trials with a low fulcrum setting while the other group was given 10 trials at a
      higher setting. The low fulcrum group had significantly greater time on balance
      but made a greater number of errors. While time on balance increased across
      trials, there was no significant reduction in the mean number of errors. There
      was an increasing negative correlation across the 10 trials between time on
      balance and number of errors, suggesting an uneven rate of skill acquisition
      among Ss and that valid criterion scores might better be acquired late in the
      learning period. 

PMID- 23952699
TI  - Constant effort during static and dynamic muscular exercise.
AB  - Ss maintained sense of effort constant over time for two tasks: static handgrip
      contractions held for 3 min., and dynamic exercise performed on a bicycle
      ergometer for 12 min. Initial force of handgrip ranged from 18-85% of maximum
      voluntary contraction, and initial power output for cycling ranged from a level
      that elicited 30% to a level that elicited 85% of maximum oxygen uptake. Except
      at the lowest levels of effort, constant-effort functions (force vs. time, power
      output vs. time) for the two tasks declined sharply at first, more slowly
      thereafter. Handgrip declined toward a steady state (asymptote) force near 15% of
      maximum voluntary contraction and functions for cycling toward a steady state
      power output that elicited oxygen uptakes equal to or less than approximately 50%
      of maximum. The two types of constant-effort functions reflect basic differences
      between static and dynamic tasks. 

PMID- 23952700
TI  - Fatigue patterns during second bouts of rhythmic and sustained exercise as a
      function of intertrial rest.
AB  - College men (N=72) were assigned at random to four permutations of activity,
      either 1 min. of sustained maximal grip flexion or 3 min. of rhythmic exercise at
      a cadence of 42 contractions/min. Each was separated by a rest interval of 5, 10,
      20, 40, 80, 160, or 320 sec. All Ss were tested with each interval of inter-bout
      recovery. Fatigue was evaluated by recording the strength exerted at each 5-sec.
      interval for the sustained bouts and each 15-sec. interval for the rhythmic
      bouts. Second-bout fatigue curves revealed that: (1) the rate of fatigue
      increased as a direct function of the length of intertrial recovery interval, (2)
      the fatigue pattern was controlled by the type of exercise performed during the
      session, (3) the asymptotic values toward which fatigue progressed were similar
      within groups but variant among the four activity permutations, and (4) within
      each family of curves there was a change in the form of the exponential equations
      required to describe the patterns of fatigue. 

PMID- 23952701
TI  - Effect of practice on consistency in performance technique.
AB  - Rapid-speed photographs taken early, midway, and late in a series of 80 trials of
      a closed skill (backward jump for distance) were analyzed to determine the effect
      of practice on within-S variability in performance technique. Means and
      variability for the distance criterion remained constant over sessions while
      variability at angle of hip and ankle during landing and variability of joint
      velocities prior to take-off decreased. Differences between kinds of closed
      skills were considered in accounting for the outcome. 

PMID- 23952702
TI  - Two-photon absorption properties of chromophores in micelles: electrostatic
      interactions.
AB  - Two-photon absorption (2PA) cross sections of neutral Coumarin 485 (C485) and
      anionic Coumarin 519 (C519(-)) solubilized in Triton X-100 (Tx-100, neutral),
      sodium dodecyl sulfate (SDS, anionic), and cetyltrimethylammonium bromide (CTAB,
      cationic) are reported. The objective of the study is to probe the influence of
      local electrostatic fields in micelles on the 2PA properties of chromophores. The
      2PA measurements have shown that the cross sections of neutral C485 are unchanged
      in different micellar environments, although the local micropolarities of
      chromophores are different. On the other hand, the 2PA cross sections of C519(-)
      are unchanged or slightly decreased in Tx-100 and SDS micelles when compared to
      water while 100% increase in 2PA cross sections was observed for C519(-) in CTAB
      micelles. The enhancement in 2PA cross section is attributed to the electrostatic
      fields arising in the Stern layer of CTAB, where C519(-) is solubilized. The
      titration measurements have shown that the 2PA enhancement is due to the
      organized medium only and not because of the simple association of C519(-) and
      the quaternary ammonium group of CTAB. From the analysis, local electric field of
      0.7 +/- 0.3 MV/cm is estimated for the Stern layer of CTAB. 

PMID- 23952703
TI  - Regulation of ABA dependent wound induced spreading cell death by MYB108.
AB  - Wounding results in the controlled cell death of a few rows of cells adjacent to
      disrupted cells resulting in physical wound closure, which combined with phenolic
      compound deposition, prevents water loss and pathogen entry. The control of these
      processes remains uncharacterized. Cell death in a mutant of Arabidopsis thaliana
      lacking BOTRYTIS SENSITIVE1/MYB108 (BOS1/MYB108) function was characterized
      utilizing physiological, cell biological and genetic methods. The bos1 mutant has
      a wound induced runaway cell death that includes enhanced reactive oxygen species
      (ROS) production that followed the extent of enhanced cell death. Exogenous
      abscisic acid (ABA) enhanced wound induced cell death in Col-0 plants and was
      sufficient to trigger cell death in bos1. Uncontrolled cell death was dependent
      of the production and perception of ABA. Furthermore, bos1 had altered
      sensitivity to and accumulation of ABA. Arabidopsis possesses a genetic program
      controlling the extent of wound inducible cell death. BOS1 acts as a negative
      regulator of ABA induced cell death, which functions in the control of this wound
      sealing program. This program is distinct from other known cell death programs in
      that it is ABA dependent, but independent of salicylate biosynthesis, ethylene,
      jasmonate, metacaspases and ROS derived from RBOHD and RBOHF. 

PMID- 23952704
TI  - Biological variation and hemoglobin A1c: relevance to diabetes management and
      complications.

PMID- 23952706
TI  - Electrochemical hydrogen insertion in substoichiometric titanium carbide TiC0.6:
      influence of carbon vacancy ordering.
AB  - Substoichiometric titanium carbide of formula TiC0.6 with different degrees of
      carbon vacancy ordering has been synthesized first by reactive sintering at high
      temperature (2100  degrees C) and then by annealing at low temperature (730 
      degrees C) for different durations. The effect of annealing on the structure of
      the carbide and its capacity to electrochemically insert hydrogen has been
      investigated. The XRD study reveals two phase transitions in the carbide during
      annealing. First, annealing of disordered TiC0.6 (space group Fm3-m) for 40 h
      leads to a trigonal superstructure of space group R3-m thanks to ordering of
      carbon vacancies. After the longest annealing time of 120 h, the structure of the
      carbide becomes cubic anew, but with a space group of Fd3-m. The electrochemical
      hydrogen insertion in these different types of TiC0.6, as studied by cyclic
      voltammetry, strongly depends on the crystalline structure of the carbide. The
      maximum storage capacity is obtained for 40 h, corresponding to the R3-m ordered
      phase. Because the R3-m structure consists of alternately empty and full (111)
      carbon atomic planes, we show that the hydrogen insertion and diffusion in the
      material is rendered possible by the presence of vacant (111) planes. This
      behavior is very similar to that of a cation-ordered manganese-nickel spinel vis
      a-vis lithium ion insertion.

PMID- 23952705
TI  - Insulin secretion improves in cystic fibrosis following ivacaftor correction of
      CFTR: a small pilot study.
AB  - OBJECTIVE: To determine whether the cystic fibrosis (CF) transmembrane
      conductance regulator (CFTR) is involved in human insulin secretion by assessing
      the metabolic impact of the new CFTR corrector-ivacaftor. METHODS: This open
      label pilot study was conducted in CF patients with the G551D mutation given new
      prescriptions for ivacaftor. At baseline and 4 wk after daily ivacaftor therapy,
      intravenous glucose tolerance tests (IVGTT) and oral glucose tolerance tests
      (OGTT) were performed. RESULTS: Five patients aged 6-52 were studied. After 1
      month on ivacaftor, the insulin response to oral glucose improved by 66-178% in
      all subjects except one with long-standing diabetes. OGTT glucose levels were not
      lower in the two individuals with diabetes or the two with normal glucose
      tolerance (NGT), but the glucose tolerance category in the subject with impaired
      glucose tolerance (IGT) improved to NGT after treatment. In response to
      intravenous glucose, the only patient whose acute insulin secretion did not
      improve had newly diagnosed, untreated CFRD. The others improved by 51-346%.
      Acute insulin secretion was partially restored in two subjects with no measurable
      acute insulin response at baseline, including the one with IGT and the one with
      long-standing diabetes. CONCLUSIONS: This small pilot study suggests there is a
      direct role of CFTR in human insulin secretion. Larger, long-term longitudinal
      studies are necessary to determine whether early initiation of CFTR correction,
      particularly in young children with CF who have not yet lost considerable beta
      cell mass, will delay or prevent development of diabetes in this high-risk
      population.

PMID- 23952707
TI  - Neohesperidin attenuates cerebral ischemia-reperfusion injury via inhibiting the
      apoptotic pathway and activating the Akt/Nrf2/HO-1 pathway.
AB  - Oxidative stress is well known to play a pivotal role in cerebral ischemia
      reperfusion injury. On the basis of this fact, antioxidative agents have been
      demonstrated to be neuroprotective. Neohesperidin (NH) is abundant in citrus
      flavonoids and possesses reactive oxygen species scavenging activity and
      neuroprotective effects in vitro. However, little is known about its effects on
      cerebral ischemia-reperfusion injury and the underlying mechanisms. In this
      study, we use a rat model of middle cerebral artery occlusion (MCAO) to
      investigate the neuroprotective effects of NH. NH significantly improved
      neurological functions and attenuated MCAO-induced infarct volume, pathological
      changes, and neuronal loss. Moreover, it enhanced antioxidant capacity and
      suppressed oxidative stress in the brain. NH inhibited the MCAO-induced
      upregulation of Bax, cytochrome c, and cleaved caspase-9 and -3, as well as the
      downregulation of Bcl-2. Interestingly, NH treatment upregulated heme oxygenase-1
      (HO-1) in a concentration-dependent manner, which was due to the NH-mediated
      activation of the protein kinase B (Akt)/nuclear factor erythroid 2-related
      factor 2 (Nrf2) pathway. NH also abolished the MCAO-induced inhibition of the
      Akt/Nrf2 pathway. In conclusion, NH attenuates cerebral ischemia-reperfusion
      injury via the inhibition of neuronal apoptosis and oxidative stress through the
      regulation of the apoptotic pathway and the Akt/Nrf2/HO-1 pathway. NH might be a
      promising preventive agent for ischemic stroke. 

PMID- 23952708
TI  - Time-resolved electrochemical quantification of azanone (HNO) at low nanomolar
      level.
AB  - Azanone (HNO, nitroxyl) is a highly reactive and short-lived compound with
      intriguing and highly relevant properties. It has been proposed to be a reaction
      intermediate in several chemical reactions and an in vivo, endogenously produced
      key metabolite and/or signaling molecule. In addition, its donors have important
      pharmacological properties. Therefore, given its relevance and elusive nature (it
      reacts with itself very quickly), the development of reliable analytical methods
      for quantitative HNO detection is in high demand for the advancement of future
      research in this area. During the past few years, several methods were developed
      that rely on chemical reactions followed by mass spectrometry, high-performance
      liquid chromatography, UV-vis, or fluorescence-trapping-based methodologies. In
      this work, our recently developed HNO-sensing electrode, based on the covalent
      attachment of cobalt(II) 5,10,15,20-tetrakis[3-(p-acetylthiopropoxy)phenyl]
      porphyrin [Co(P)] to a gold electrode, has been thoroughly characterized in terms
      of sensibility, accuracy, time-resolved detection, and compatibility with complex
      biologically compatible media. Our results show that the Co(P) electrode: (i)
      allows time-resolved detection and kinetic analysis of the electrode response
      (the underlying HNO-producing reactions can be characterized) (ii) is able to
      selectively detect and reliably quantify HNO in the 1-1000 nM range, and (iii)
      has good biological media compatibility (including cell culture), displaying a
      lack of spurious signals due to the presence of O2, NO, and other reactive
      nitrogen and oxygen species. In summary, the Co(P) electrode is to our knowledge
      the best prospect for use in studies investigating HNO-related chemical and
      biological reactions. 

PMID- 23952709
TI  - Pathology of two forms of shell disease of the American lobster Homarus
      americanus Milne Edwards in Atlantic Canada.

PMID- 23952710
TI  - Profile of the Belgian dermatologist: results of an online survey.

PMID- 23952711
TI  - Adapting enzyme-based microbial water quality analysis to remote areas in low
      income countries.
AB  - Enzyme-substrate microbial water tests, originally developed for efficiency gains
      in laboratory settings, are potentially useful for on-site analysis in remote
      settings. This is especially relevant in developing countries where water quality
      is a pressing concern and qualified laboratories are rare. We investigated one
      such method, Colisure, first for sensitivity to incubation temperatures in order
      to explore alternative incubation techniques appropriate for remote areas, and
      then in a remote community of Zambia for detection of total coliforms and
      Escherichia coli in drinking-water samples. We sampled and analyzed 352 water
      samples from source, transport containers and point-of-use from 164 random
      households. Both internal validity (96-100%) and laboratory trials (zero false
      negatives or positives at incubation between 30 and 40  degrees C) established
      reliability under field conditions. We therefore recommend the use of this and
      other enzyme-based methods for remote applications. We also found that most water
      samples from wells accessing groundwater were free of E. coli whereas most
      samples from surface sources were fecally contaminated. We further found very low
      awareness among the population of the high levels of recontamination in household
      storage containers, suggesting the need for monitoring and treatment beyond the
      water source itself. 

PMID- 23952713
TI  - Effects of varied sequence pattern on the self-assembly of amphipathic peptides.
AB  - Amphipathic peptides have an increased propensity to self-assemble into amyloid
      like beta-sheet fibrils when their primary sequence pattern consists of
      alternating hydrophobic and hydrophilic amino acids. These fibrils adopt a
      bilayer architecture composed of two beta-sheets laminated to bury the
      hydrophobic side chains of the beta-sheet in the bilayer interior, leaving the
      hydrophilic side chains exposed at the bilayer surface. In this study, the
      effects of altering the sequence pattern of amphipathic peptides from strictly
      alternating hydrophobic/hydrophilic repeats to more complex patterning of
      hydrophobic and hydrophilic residues on self-assembly of the resulting sequences
      is reported. Self-assembly of the Ac-(FKFE)2-NH2 peptide was compared to that of
      four related sequences with varied amino acid sequence patterning: Ac-(FK)2(FE)2
      NH2, Ac-KEFFFFKE-NH2, Ac-(KFFE)2-NH2, and Ac-FFKEKEFF-NH2. The Ac-(FKFE)2-NH2 and
      Ac-(FK)2(FE)2-NH2 peptides effectively self-assembled at high (1.0 mM) and low
      (0.2 mM) concentrations (pH 3-4) into beta-sheet nanoribbons that were 8 and 4 nm
      wide, respectively. The Ac-KEFFFFKE-NH2 peptide failed to self-assemble at low
      concentration (pH 3-4), but self-assembled into distinct nanotapes that were ~20
      nm in width at high concentration. Ac-(KFFE)2-NH2 and Ac-FFKEKEFF-NH2 failed to
      self-assemble into fibril/tape-like materials at either high or low concentration
      at pH 3-4, although Ac-FFKEKEFF-NH2 formed micelle-like aggregates at higher
      concentrations. At neutral pH, similar self-assembly behavior was observed for
      each peptide as was observed at acidic pH. An exception was the Ac-FFKEKEFF-NH2
      peptide, which formed ~20 nm nanotapes at neutral pH. These results indicate that
      amino acid sequence patterns exert a profound influence on self-assembly
      propensity and morphology of the resulting materials even when the overall
      hydrophobicity or charge of the related peptides are identical. Sequence pattern
      variation can thus be exploited as a variable in the creation of novel materials
      composed of self-assembled peptides.

PMID- 23952712
TI  - Image-guided local delivery strategies enhance therapeutic nanoparticle uptake in
      solid tumors.
AB  - Nanoparticles (NP) have emerged as a novel class of therapeutic agents that
      overcome many of the limitations of current cancer chemotherapeutics. However, a
      major challenge to many current NP platforms is unfavorable biodistribution, and
      limited tumor uptake, upon systemic delivery. Delivery, therefore, remains a
      critical barrier to widespread clinical adoption of NP therapeutics. To overcome
      these limitations, we have adapted the techniques of image-guided local drug
      delivery to develop nanoablation and nanoembolization. Nanoablation is a tumor
      ablative strategy that employs image-guided placement of electrodes into tumor
      tissue to electroporate tumor cells, resulting in a rapid influx of NPs that is
      not dependent on cellular uptake machinery or stage of the cell cycle.
      Nanoembolization involves the image-guided delivery of NPs and embolic agents
      directly into the blood supply of tumors. We describe the design and testing of
      our innovative local delivery strategies using doxorubicin-functionalized
      superparamagnetic iron oxide nanoparticles (DOX-SPIOs) in cell culture, and the
      N1S1 hepatoma and VX2 tumor models, imaged by high resolution 7T MRI. We
      demonstrate that local delivery techniques result in significantly increased
      intratumoral DOX-SPIO uptake, with limited off-target delivery in tumor-bearing
      animal models. The techniques described are versatile enough to be extended to
      any NP platform, targeting any solid organ malignancy that can be accessed via
      imaging guidance. 

PMID- 23952715
TI  - Influence of renal sympathetic denervation on quality of life.
AB  - BACKGROUND: Therapy-resistant arterial hypertension causing psychosocial stress
      and is associated with cardiovascular morbidity and mortality. The aim of the
      study was to evaluate the effect on quality of life (QoL) in patients with
      resistant hypertension undergoing renal sympathetic denervation (RSD). METHODS
      AND RESULTS: We analyzed responses to the SF-36 Quality of Life Questionnaire
      provided by patients with resistant arterial hypertension after RSD. Thirty
      consecutive patients from 2 centers were included in this study, from October
      2011 until February 2012. The phone interview was performed after the 3-month
      follow-up. A significant reduction (26 +/- 13.5 mmHg) in systolic blood pressure
      (BP) was detected at the 3-month follow-up (142.0 +/- 15.1 mmHg vs 168.0 +/- 13.7
      mmHg; P < 0.001). Seventy-five percent of the patients indicated that their
      health situation was a lot better (better, 21%; equal to, 4%) 3 months after RSD
      compared to the time before the therapeutic procedure. Furthermore, the majority
      of patients felt full of pep (always, 29%; mostly, 58%; quite often, 8%;
      sometimes, 4%), and full of energy (always, 25%; mostly, 54%; quite often, 16.7%;
      sometimes, 4.2%) after the procedure. Recipients of RSD indicated that they felt
      more light and healthy, and nearly all recipients (93%) described a loss of
      anxiety and indisposition. CONCLUSIONS: This investigation revealed that
      sufficient BP reduction by RSD and time following therapeutic success lead to
      significant improvements in patient QoL.

PMID- 23952714
TI  - The sacred lotus genome provides insights into the evolution of flowering plants.
AB  - Sacred lotus (Nelumbo nucifera) is an ornamental plant that is also used for food
      and medicine. This basal eudicot species is especially important from an
      evolutionary perspective, as it occupies a critical phylogenetic position in
      flowering plants. Here we report the draft genome of a wild strain of sacred
      lotus. The assembled genome is 792 Mb, which is approximately 85-90% of genome
      size estimates. We annotated 392 Mb of repeat sequences and 36,385 protein-coding
      genes within the genome. Using these sequence data, we constructed a phylogenetic
      tree and confirmed the basal location of sacred lotus within eudicots.
      Importantly, we found evidence for a relatively recent whole-genome duplication
      event; any indication of the ancient paleo-hexaploid event was, however, absent.
      Genomic analysis revealed evidence of positive selection within 28 embryo
      defective genes and one annexin gene that may be related to the long-term
      viability of sacred lotus seed. We also identified a significant expansion of
      starch synthase genes, which probably elevated starch levels within the rhizome
      of sacred lotus. Sequencing this strain of sacred lotus thus provided important
      insights into the evolution of flowering plant and revealed genetic mechanisms
      that influence seed dormancy and starch synthesis.

PMID- 23952716
TI  - Being in transit and in transition: the experience of time at the place, when
      living with severe incurable disease--a phenomenological study.
AB  - The aim of this study is to describe the experience of time as it presents itself
      at the place being situated when living with severe incurable disease and
      receiving palliative care. The empirical data consist of 26 open-ended interviews
      with 23 patients receiving palliative care at home, at a palliative day care, in
      a palliative bed unit in hospital or in a nursing home in Norway. A common
      meaning of a shifting space for living emerged from the analysis and was revealed
      through three different aspects: (i) Transition from a predictable to an
      unpredictable time: To live with severe incurable disease marks a transition to a
      changed life involving an ongoing weakened and altered body with bothersome
      symptoms making experience of time different and unpredictable. (ii) Transition
      between a safe and unsafe time: When time is unpredictable, feeling safe is
      revealed as essential to how time is experienced at the place being situated.
      (iii) To be in transition from a homely to a homeless existence: In a time of
      increased bodily weakness, unpredictable ailments and displacements, the sense of
      belonging to the place is revealed as significant to the experience of time. Not
      knowing where to be in a time of change is like an existential cry of distress
      where the foothold in existence is lost. The findings are discussed and
      interpreted as an embodied experience originating from the passage of time
      continually affecting life sometimes so fundamentally that it marks a transition
      to a changed space of life that is reflected in the experience of time. 

PMID- 23952717
TI  - HIV antiretroviral resistance mutations among antiretroviral treatment-naive and 
      experienced patients in South Korea.
AB  - The purpose of this study was to assess the prevalence and characteristics of HIV
      drug resistance mutations among antiretroviral therapy (ART)-naive and ART
      experienced patients in South Korea. A total of 50 ART-naive and 34 ART
      experienced Korean HIV-1-infected patients who visited an urban hospital from
      February 2007 to March 2011 were included. Most patients (86.9%) were infected
      with clade B HIV-1. Six (12%) ART-naive and 22 (64.7%) ART-experienced patients
      had HIV strains with resistance mutations. Among ART-naive patients, V179D was
      the most common mutation, being found in five ART-naive patients. Among ART
      experienced patients, M184V was the most common mutation. Eight of 34 ART
      experienced patients had thymidine analogue mutations (TAMs). The prevalence of
      drug-resistant HIV-1 in ART-naive patients was higher than in previous reports,
      and 50% of patients with virologic failure harbored strains with multiple
      resistance mutations. HIV drug resistance testing should be recommended to guide
      therapy of ART-naive patients in South Korea.

PMID- 23952718
TI  - A melatonin-based fluorescence method for the measurement of mitochondrial
      complex III function in intact cells.
AB  - Mitochondrial complex III (MC-3) plays a pivotal role in electron transfer and
      oxidative phosphorylation. Impaired MC-3 functions may contribute to a variety of
      diseases by interrupting normal bioenergetics and increasing reactive oxygen
      production and oxidative stress. Currently, MC-3 function is assessed by
      measuring the cytochrome c reductase activity spectrophotometrically in isolated
      mitochondria or MC-3. The cytoplasmic microenvironment critical for mitochondrial
      complex functions may be depleted during these isolation processes. The
      development of a reliable method to measure MC-3 activities in intact cells or
      tissues is highly desirable. This report describes a novel fluorescence-based
      method to assess MC-3 functions, i.e., Qi site electron transfer, in the intact
      cells. Human mesangial and teratocarcinoma NT2 cells were used to demonstrate
      that melatonin-induced oxidation of 2',7'-dichlorodihydrofluorescein (H2 DCF) was
      inhibited by antimycin A, the MC-3 Qi site-specific inhibitor, but not by
      myxothiazol, the MC-3 Qo site-specific inhibitor, nor rotenone, the mitochondrial
      complex I inhibitor. These results indicate that melatonin-induced oxidation of
      H2 DCF is reflecting MC-3 Qi site electron transfer activities. Modifying
      structures of the side groups at the R3 and R5 positions of the indole ring of
      melatonin diminished its efficacy for inducing H2 DCF oxidation, suggesting a
      specific interaction of melatonin with the MC-3 Qi site. These results suggest
      that the fluorogenic property of melatonin-induced H2 DCF oxidation provides a MC
      3 Qi site electron transfer-specific measurement in intact cells. Interestingly,
      using this method, the Qi site electron transfer activity in transformed or
      immortalized cells was found to be significantly higher than the nontransformed
      cells. 

PMID- 23952719
TI  - Symptomatology and functional outcome in mild traumatic brain injury: results
      from the prospective TRACK-TBI study.
AB  - Mild Traumatic Brain Injury (mTBI), or concussion, is a major public health
      concern. There is controversy in the literature regarding the true incidence of
      postconcussion syndrome (PCS), with the constellation of physical, cognitive,
      emotional, and sleep symptoms after mTBI. In the current study, we report on the
      incidence and evolution of PCS symptoms and patient outcomes after mTBI at 3, 6,
      and 12 months in a large, prospective cohort of mTBI patients. Participants were
      identified as part of the prospective, multi-center Transforming Research and
      Clinical Knowledge in Traumatic Brain Injury Study. The study population was mTBI
      patients (Glasgow Coma Scale score of 13-15) presenting to the emergency
      department, including patients with a negative head computed tomography
      discharged to home without admission to hospital; 375 mTBI subjects were included
      in the analysis. At both 6 and 12 months after mTBI, 82% (n=250 of 305 and n=163
      of 199, respectively) of patients reported at least one PCS symptom. Further,
      44.5 and 40.3% of patients had significantly reduced Satisfaction With Life
      scores at 6 and 12 months, respectively. At 3 months after injury, 33% of the
      mTBI subjects were functionally impaired (Glasgow Outcome Scale-Extended score
      <=6); 22.4% of the mTBI subjects available for follow-up were still below full
      functional status at 1 year after injury. The term "mild" continues to be a
      misnomer for this patient population and underscores the critical need for
      evolving classification strategies for TBI for targeted therapy.

PMID- 23952720
TI  - Massive cerebral involvement in fat embolism syndrome and intracranial pressure
      management.
AB  - Fat embolism syndrome (FES) is a common clinical entity that can occasionally
      have significant neurological sequelae. The authors report a case of cerebral fat
      embolism and FES that required surgical management of intracranial pressure
      (ICP). They also discuss the literature as well as the potential need for
      neurosurgical management of this disease entity in select patients. A 58-year-old
      woman presented with a seizure episode and altered mental status after suffering
      a right femur fracture. Head CT studies demonstrated hypointense areas consistent
      with fat globules at the gray-white matter junction predominantly in the right
      hemisphere. This CT finding is unique in the literature, as other reports have
      not included imaging performed early enough to capture this finding. Brain MR
      images obtained 3 days later revealed T2-hyperintense areas with restricted
      diffusion within the same hemisphere, along with midline shift and subfalcine
      herniation. These findings steered the patient to the operating room for
      decompressive hemicraniectomy. A review of the literature from 1980 to 2012
      disclosed 54 cases in 38 reports concerning cerebral fat embolism and FES.
      Analysis of all the cases revealed that 98% of the patients presented with mental
      status changes, whereas only 22% had focal signs and/or seizures. A good outcome
      was seen in 57.6% of patients with coma and/or abnormal posturing on presentation
      and in 90.5% of patients presenting with mild mental status changes, focal
      deficits, or seizure. In the majority of cases ICP was managed conservatively
      with no surgical intervention. One case featured the use of an ICP monitor, while
      none featured the use of hemicraniectomy. 

PMID- 23952722
TI  - Substance use disorders among registered nurses: prevalence, risks and
      perceptions in a disciplinary jurisdiction.
AB  - AIM: To investigate substance use disorders, impaired practice and health risks
      among nurses in a disciplinary jurisdiction. BACKGROUND: The relationship between
      substance-related risks to patient safety, nurse health and discipline is
      understudied. METHOD: A convenience sample of 4064 registered nurses responded to
      an Internet survey in 2010. Self-reports were given to psychometrically robust
      measures of health, substance use disorders and organisational support.
      Perceptions on the treatment and disposition of impaired nurses were also asked.
      RESULTS: The prevalence of substance use disorders was similar to the general
      population. Most nurses' coded high risk for impaired practices were working,
      unknown by their employer/regulator and not receiving treatment. When compared
      with nurse-peers, their health and organisational support were compromised. Nurse
      peers viewed impaired nurses as having a treatable illness that their
      employers/regulators should assist and afford confidentiality. CONCLUSIONS: In
      this jurisdiction, discipline was not rated as effective for risk mitigation,
      supportive of nurses with substance use disorders or in alignment with nurse
      perceptions. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers play a
      significant role in addressing substance-related issues among nurses and can be
      key to influencing the outcomes of these difficult situations. For these reasons,
      it is important they recognize the ineffectiveness of discipline for substance
      related risk mitigation.

PMID- 23952723
TI  - Efficacy of combined therapy with paclitaxel and low-level ultrasound in human
      chronic myelogenous leukemia cell line K562.
AB  - BACKGROUND: Sonochemotherapy, which applies ultrasound in cancer chemotherapy,
      has been proven to be a promising therapeutic modality by some previous
      researches. PURPOSE: To investigate the interaction between an antineoplastic
      agent - paclitaxel (PTX) and low-level ultrasound in human chronic myelogenous
      leukemia cell line K562, their combined efficacy, and the potential mechanisms in
      sonochemotherapy. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide (MTT) analysis and Guava Viacount assay were adopted to examine cell
      viability. Apoptosis was analyzed using Annexin V-PE/7-amino-actinomycin D
      staining. Changes in plasma membrane permeability were monitored by FD500-uptake
      and lactate dehydrogenase (LDH) release assays. Additionally, the ultrastructure
      changes were evaluated under scanning electron microscope (SEM). RESULTS: When 5
      ng/ml PTX was combined with sonication at Load Power (LP) = 2 W, the expected
      synergistic effects on cell viability loss (p < 0.05) and apoptosis enhancement
      could be significantly detected, the plasma membrane permeability showed the best
      response, and relatively serious cell damages were observed under SEM.
      CONCLUSION: The interaction between these two therapies depended on specific
      parameter settings, such as PTX dose and ultrasound intensity. Under synergistic
      conditions, ultrasound significantly potentiated the efficacies of PTX, including
      cytotoxicity, apoptosis and cell damage induction, which may be due to the
      enhanced membrane permeability and the increased intracellular PTX level.

PMID- 23952724
TI  - Arterial peculiarities of the thoracolumbar spinal cord in rabbit.
AB  - The aim of this study was to investigate the arterial blood supply of the
      thoracolumbar spinal cord in rabbit. The study was carried out on twenty adult
      New Zealand white rabbits. Ten rabbits were used in the corrosion technique and
      ten rabbits in the dissection technique. After the killing, the vascular network
      was perfused with saline. Batson's corrosion casting kit no. 17 (c) was used as a
      casting medium. After polymerisation of the medium, in ten rabbits the maceration
      was carried out in KOH solution, and in ten other rabbits, formaldehyde was
      injected by the dissection technique into the vertebral canal. We found high
      variability of segmental arteries supplying blood to the spinal cord. There are
      12 intercostal arteries and 1 costo-abdominal artery. Dorsal branches arising
      from the dorsal surface of the aorta thoracica were found as follows: in 70% of
      the cases, 9 pairs were present; in 20% of the cases 8 pairs; and in 10% of the
      cases 10 pairs. The paired arteriae lumbales were present in 6 pairs in 90% of
      the cases and in 5 pairs in 10% of the cases. On the dorsal surface of spinal
      cord, we found two irregular longitudinal arteries in 70% of the cases, no
      longitudinal arteries in 20% of the cases and three irregular longitudinal
      arteries in 10% of the cases receiving dorsal branches of rami spinales. Among
      the dorsal branches observed in the thoracic region, 60.5% were left-sided, 39.5%
      right-sided and in the lumbar region, 52.5% were left-sided and 47.5% right
      sided. 

PMID- 23952725
TI  - Higher processes in motor learning.
AB  - A linear displacement task was used to study the effects of post-KR verbal
      activity and the time of its introduction in the learning process on the
      acquisition of a simple discrete motor task. The temporal occurrence of the
      interpolated act was systematically varied (3 and 10 sec. immediately following
      KR). Reading polysyllables during the post-KR delay interval interfered with the
      learning process. Interference occurred whether the post-KR delay interval lasted
      3 or 10 sec. 

PMID- 23952726
TI  - Exposure and occluded duration effects in a ball-catching skill.
AB  - Male Ss (N=48) from a university population attempted single-handed catches of
      lawn tennis balls delivered by a mechanical projection machine. The within-and
      between-S variables in a split-plot factorial design were the period for which
      the ball was illuminated (VP) and the subsequent period of occlusion (OP). Both
      variables and their interaction were significant sources of variation. Generally
      the effect of VP diminished as OP was extended. This was discussed in terms of
      (1) information processing time and (2) motion prediction. With respect to the
      first issue, the most important variable was not VP, but a composite term VP +
      OP. On the second issue, support was provided for an hypothesis to account for
      prediction error raised in a previous study. 

PMID- 23952727
TI  - Variable and constant performance errors within a group of individuals.
AB  - The correct individual single score for a within-S series of errors e about the
      target (for k trials) is E= ??e(2) /k= ?V(2) +C(2); the commonly used absolute
      error AE under-represents or deletes the variable error component V. In
      correlational analysis, the constant error score should be C absolute and V
      should be used unsquared in order to avoid curvilinearity; in general, r patterns
      across Ss are not predictable from within-Ss relations. While V and C are
      necessarily independent within Ss, they usually exhibit substantial correlation
      across Ss; evaluation of the role of each is sometimes important. Linearity of
      regression is demanded; it, rather than non-skewness, is shown to be the
      important assumption in using r. If relations involving algebraic C are of
      interest, the correlation index may be required because of U-shaped regression.
      Several common statistical misinterpretations are discussed. 

PMID- 23952729
TI  - Amount and order of redundancy as determinants of continuous tracking
      performance.
AB  - Previous studies manipulating redundancy in tracking experiments used discrete
      rather than continuous tracking tasks. A methodology is presented for
      manipulating redundancy in continuous input tracks in order to compare the
      influence of redundancy on continuous tracking performance to that found
      previously using discrete tracking tasks. Three orders of redundancy were
      introduced in continuous tracks. Within each order of redundancy, five different
      amounts of redundancy were used by manipulating the sequential probabilities of
      the tracks' maximum amplitude values. The analysis of response lags and error
      data indicated that Ss did not respond as predicted to the conditional
      probabilities of amplitude heights existing in the tracks, even when the
      probabilities were relatively high, but rather responded to different aspects of
      the tracks. These results were interpreted in terms of the unique characteristics
      of the continuous input and the postulated sampling strategy employed by Ss. 

PMID- 23952728
TI  - Peripheral signal detection and concurrent compensatory tracking.
AB  - A Mackworth-clock monitoring task was introduced into a standard compensatory
      tracking task located at different lateral positions in S's visual field, while
      the tracking task was located in the center of the visual field. The variables
      tracking frequency and monitor position were hypothesized to produce mutual
      interference in the dual-task arrangement, and the spatial separation of the two
      tasks was assumed to adversely affect peripheral signal detection. As the
      tracking frequency increased, peripheral monitoring performance remained high,
      while tracking accuracy was reduced. The position of the monitor task did not
      affect monitoring performance, but did influence tracking accuracy at the low
      tracking frequency. A divided-attention effect was found with respect to the
      monitoring task when both tasks were located directly in S's field of view. Eye
      movement data provided some support for the notion of a functional visual field. 

PMID- 23952730
TI  - Behavioral and neurological parameters of the nerve compression block.
AB  - The nerve-compression block has been used to investigate movement control in the
      absence of kinesthetic information. Implicit is the assumption that tactile and
      kinesthetic sensation are eliminated 5 to 10 min. prior to motor function. Motor
      fibers in the ulnar and median nerves of the upper preferred limb were tested at
      systematic intervals throughout the duration of the block application. When
      kinesthetic cut-off was assigned, Ss performed three tapping trials with vision
      and audition eliminated. Progressive reduction in nerve-conduction parameters
      (motor nerve conduction velocity and amplitude of the muscle action potential)
      occurred across and below the block, with significant decrements occurring as
      early as 15 min. Results indicated that motor impairment was a confounding factor
      in the use of the nerve block technique. 

PMID- 23952731
TI  - Effect of four fatigue levels on performance and learning of a novel dynamic
      balance skill.
AB  - This study was to investigate the effect of fatigue on the performance and
      learning of the Bachman ladder task to determine if the relationship between
      activation and both the performance and learning data would support the inverted
      U theory. Male Ss (N=48) were randomly assigned to four groups. A level of
      fatigue as determined by HR (Control, 120 BPM, 150 BPM, and 180 BPM) was assigned
      to each group. Each S was fatigued to his assigned level prior to the task and
      following each trial, was given 20 trials on Day 1 to learn the task while at his
      designated level, and then was given 20 additional trials on Day 2 under control
      conditions. On Day 1 150 and 180 BPM impaired performance of the motor task. The
      learning score data indicated that 150 and 180 BPM had a detrimental effect on
      learning of the task. Both the activation-performance and the activation-learning
      relationships partially supported the inverted-U theory. 

PMID- 23952732
TI  - Visual and kinesthetic components of pursuit-tracking performance.
AB  - Ss (N=75) were trained on a pursuit rotor for 10 trials with ambient illumination
      from a strobe light flashing at frequencies of either 2, 5, 10, 15, or 20/sec. A
      transfer trial followed, with a strobe flashing frequency of 10/sec for all Ss.
      Results supported hypotheses derived from Adams' (1971) closed-loop theory of
      motor learning that (a) performance would improve during training as a function
      of amount of visual feedback available, and that (b) if after training visual
      feedback was reduced, performance would be maintained to the extent that reliance
      upon kinesthetic feedback had been learned as an alternate compensatory feedback
      loop. 

PMID- 23952733
TI  - Bilateral transfer of inhibition in the motor learning of schizophrenics and
      normals.
AB  - Bilateral transfer of the effects of massed practice in motor learning was
      evaluated for an adjusted sample of 36 chronic undifferentiated schizophrenics
      and 36 normal controls. Ss were trained and tested on a rotary pursuit task under
      two bilateral transfer conditions-Rest and No-Rest- and one non-transfer Control
      condition. Normal Ss demonstrated positive reminiscence scores in the Rest
      condition and significant transfer of inhibitory effects in the No-Rest
      condition. Schizophrenics, on the other hand, showed no significant transfer of
      inhibition. The results were discussed as supporting the hypothesis of a
      proprioceptive deficit in schizophrenia involving central integrating mechanisms.
      Such findings also suggested that a proprioceptive deficit might be a significant
      underlying factor in the cognitive dysfunction and body image disturbances of
      schizophrenia, processes which also can be explained by impairment in central
      integrating mechanisms. 

PMID- 23952734
TI  - Dynamical study of impurity effects on bipolaron-bipolaron and bipolaron-polaron
      scattering in conjugated polymers.
AB  - Combining the one-dimensional tight-binding Su-Schrieffer-Heeger (SSH) model and
      the extended Hubbard model (EHM), the scattering of two oppositely charged
      bipolarons and a bipolaron-polaron pair is investigated under the influence of
      impurity effects using a nonadiabatic evolution method. These novel results for
      bipolarons show that the oppositely charged quasi-particles scatter into a mixed
      state composed of bipolarons and excitons. The excitation yield depends
      sensitively on the strength of the applied electric field. In the presence of an
      impurity, the critical electric field regime for formation of a state composed by
      bipolarons and excitons is increased. Additionally, we were able to obtain
      critical values of electric fields that played the role of drastically modifying
      the system dynamics. These facts suggest that the scattering between bipolarons
      and a bipolaron-polaron pair in the presence of impurities is crucial for the
      understanding of electroluminescence in optoelectronics devices, such as polymer
      light emitting diodes. 

PMID- 23952735
TI  - p28, an anionic cell-penetrating peptide, increases the activity of wild type and
      mutated p53 without altering its conformation.
AB  - p28, a cell penetrating peptide, binds to the DNA binding domain (DBD) of p53,
      inducing a post-translational increase in intracellular levels of wild type and
      mutant p53 activating pathways that inhibit cancer cell proliferation at G2/M.
      Cancer cells respond to p28 with an increase in p53 activity, except when
      mutations either alter DNA contact or completely unfold the DBD. The increase in
      p53 activity is accompanied by a significant reduction in the level of the E3
      ligase COP1, with no alteration in p53 conformation. This suggests p28 can
      activate p53 over a wide range of conformational mutations by inhibiting the
      binding of COP1 to p53. 

PMID- 23952736
TI  - The actin cytoskeleton is a suppressor of the endogenous skewing behaviour of
      Arabidopsis primary roots in microgravity.
AB  - Before plants can be effectively utilised as a component of enclosed life-support
      systems for space exploration, it is important to understand the molecular
      mechanisms by which they develop in microgravity. Using the Biological Research
      in Canisters (BRIC) hardware on board the second to the last flight of the Space
      Shuttle Discovery (STS-131 mission), we studied how microgravity impacts root
      growth in Arabidopsis thaliana. Ground-based studies showed that the actin
      cytoskeleton negatively regulates root gravity responses on Earth, leading us to
      hypothesise that actin might also be an important modulator of root growth
      behaviour in space. We investigated how microgravity impacted root growth of wild
      type (ecotype Columbia) and a mutant (act2-3) disrupted in a root-expressed
      vegetative actin isoform (ACTIN2). Roots of etiolated wild-type and act2-3
      seedlings grown in space skewed vigorously toward the left, which was unexpected
      given the reduced directional cue provided by gravity. The left-handed
      directional root growth in space was more pronounced in act2-3 mutants than wild
      type. To quantify differences in root orientation of these two genotypes in
      space, we developed an algorithm where single root images were converted into
      binary images using computational edge detection methods. Binary images were
      processed with Fast Fourier Transformation (FFT), and histogram and entropy were
      used to determine spectral distribution, such that high entropy values
      corresponded to roots that deviated more strongly from linear orientation whereas
      low entropy values represented straight roots. We found that act2-3 roots had a
      statistically stronger skewing/coiling response than wild-type roots, but such
      differences were not apparent on Earth. Ultrastructural studies revealed that
      newly developed cell walls of space-grown act2-3 roots were more severely
      disrupted compared to space-grown wild type, and ground control wild-type and
      act2-3 roots. Collectively, our results provide evidence that, like root gravity
      responses on Earth, endogenous directional growth patterns of roots in
      microgravity are suppressed by the actin cytoskeleton. Modulation of root growth
      in space by actin could be facilitated in part through its impact on cell wall
      architecture. 

PMID- 23952737
TI  - Thelohanellus testudineus n. sp. (Myxosporea: Bivalvulida) infecting the skin of
      allogynogenetic gibel carp Carassius auratus gibelio (Bloch) in China.
AB  - A Thelohanellus species was encountered during a survey on Thelohanellus
      diversity of Carassius auratus gibelio (Bloch) in China. The infection is
      characterized by the presence of large cysts of 1.4-3.2 cm in diameter in the
      skin of host. Mature spores were ampullaceous in frontal view and testudinate in
      lateral view, measuring 19.7 +/- 0.7 (18.6-20.8) MUm long, 7.6 +/- 0.4 (6.6-8.4)
      MUm wide and 7.3 +/- 0.5 (6.6-8.8) MUm thick. The single polar capsule was
      elongated pyriform, with 11.1 +/- 0.5 (10.0-11.9) MUm long and 5.3 +/- 0.3 (4.3
      5.8) MUm wide. Polar filaments coiled with 7-8 turns. Scanning electron
      microscopy revealed a smooth spore surface with flat side and convex side. The
      sutural line was straight or 'S' like, running near the middle of the valves.
      Histologically, the large cysts consisting of numerous small plasmodia developed
      in the dermis of the skin. The BLAST search indicated that the newly obtained
      ssrRNA gene sequences did not match any available sequences in GenBank and
      phylogenetic analysis placed it in the Thelohanellus clade. Based on morphology
      and molecular differences with reported Thelohanellus spp., this parasite was
      described as a new species of genus Thelohanellus.

PMID- 23952738
TI  - Antitumor and scavenging radicals activities of some polyphenols related to
      dehydroabietylamine derivatives.
AB  - A novel series of polyphenols 4-9 were synthesized by the reaction of catechol
      with dehydroabietylamine derivatives. The antitumor activities of these compounds
      against L02 and HepG2 cells were investigated. Among them, compounds 4, 5, and 9
      can inhibit HepG2 cells viability, but have lower inhibitory effect on L02 cells
      in the same concentration, indicating their potential for further development.
      Meanwhile, the novel series of polyphenols exhibited stronger radical-scavenging
      activities than the control groups. 

PMID- 23952739
TI  - Comparative effect of topical silicone gel and topical tretinoin cream for the
      prevention of hypertrophic scar and keloid formation and the improvement of
      scars.
AB  - BACKGROUND: Numerous modalities have been used to treat keloids and hypertrophic
      scars; however, optimal treatment has not yet been established. Therefore,
      prevention is the mainstay. Recently, silicone gel and tretinoin cream have been
      shown to be useful for the prevention of hypertrophic scars and keloids. However,
      there has been no comparative study of the two topical agents thus far.
      OBJECTIVE: To determine and compare the effectiveness of silicone gel and
      tretinoin cream for the prevention of hypertrophic scars and keloids resulting
      from postoperative wounds and for scar improvement. METHOD: This study included
      26 patients with 44 different wounds. The postoperative wounds were divided into
      two treatment groups and one control group. The patients in the first and second
      treatment group applied silicone gel and tretinoin cream, respectively, twice a
      day on their wounds after their stitches were removed. In contrast, the control
      group patients did not apply anything. We used the Modified Vancouver Scar Scale
      to quantitatively examine the effectiveness of silicone gel and tretinoin cream
      just after stitches removal, and at 4, 8, 12 and 24 weeks after removal of the
      stitches. RESULTS: The silicone gel and tretinoin cream effectively prevented
      hypertrophic scars and keloids and improved scar effects in the two treatment
      groups compared with those in the control group. However, no significant
      difference was noted between the two treatment groups. CONCLUSION: To prevent
      hypertrophic scars and keloids and improve scars after surgery, application of a
      silicone gel or a tretinoin cream to the wounds is needed.

PMID- 23952740
TI  - Effect of ingested tungsten oxide (WOx) nanofibers on digestive gland tissue of
      Porcellio scaber (Isopoda, Crustacea): fourier transform infrared (FTIR) imaging.
AB  - Tungsten nanofibers are recognized as biologically potent. We study deviations in
      molecular composition between normal and digestive gland tissue of WOx nanofibers
      (nano-WOx) fed invertebrate Porcellio scaber (Iosopda, Crustacea) and revealed
      mechanisms of nano-WOx effect in vivo. Fourier Transform Infrared (FTIR) imaging
      performed on digestive gland epithelium was supplemented by toxicity and
      cytotoxicity analyses as well as scanning electron microscopy (SEM) of the
      surface of the epithelium. The difference in the spectra of the Nano-WOx treated
      and control cells showed up in the central region of the cells and were related
      to lipid peroxidation, and structural changes of nucleic acids. The conventional
      toxicity parameters failed to show toxic effects of nano-WOx, whereas the
      cytotoxicity biomarkers and SEM investigation of digestive gland epithelium
      indicated sporadic effects of nanofibers. Since toxicological and cytological
      measurements did not highlight severe effects, the biochemical alterations
      evidenced by FTIR imaging have been explained as the result of cell protection
      (acclimation) mechanisms to unfavorable conditions and indication of a
      nonhomeostatic state, which can lead to toxic effects. 

PMID- 23952742
TI  - In situ repair of high-performance, flexible nanocrystal electronics for large
      area fabrication and operation in air.
AB  - Colloidal semiconductor nanocrystal (NC) thin films have been integrated in light
      emitting diodes, solar cells, field-effect transistors (FETs), and flexible,
      electronic circuits. However, NC devices are typically fabricated and operated in
      an inert environment since the reactive surface and high surface-to-volume ratio
      of NC materials render them sensitive to oxygen, water, and many solvents. This
      sensitivity has limited device scaling and large-scale device integration
      achievable by conventional fabrication technologies, which generally require
      ambient air and wet-chemical processing. Here, we present a simple, effective
      route to reverse the detrimental effects of chemical and environmental exposure,
      by incorporating, in situ, a chemical agent, namely, indium metal, which is
      thermally triggered to diffuse and repair the damage. Taking advantage of the
      recovery process, CdSe NC FETs are processed in air, patterned using the solvents
      of lithography, and packaged by atomic layer deposition to form large-area and
      flexible high-performance NC devices that operate stably in air. 

PMID- 23952741
TI  - Expansion of hepatic stem cell compartment boosts liver regeneration.
AB  - The hepatic stem cells reside periportally forming the canals of Hering in normal
      liver. They can be identified by their unique immunophenotype in rat. The oval
      cells, the progenies of stem cells invade deep the liver parenchyma after
      activation and differentiate into focally arranged small-and eventually
      trabecularly ordered regular hepatocytes. We have observed that upon the
      completion of intense oval cell reactions narrow ductular structures are present
      in the parenchyma, we propose to call them parenchymal ductules. These
      parenchymal ductules have the same immunophenotype [cytokeratin (CK)7
      /CK19+/alpha-fetoprotein (AFP)-/delta-like protein (DLK)-] as the resting stem
      cells of the canals of Hering, but different from them reside scattered in the
      parenchyma. In our present experiments, we have investigated in an in vivo
      functional assay if the presence of these parenchymal ductules has any impact on
      a progenitor cell driven regeneration process. Parenchymal ductules were induced
      either by an established model of oval cell induction consisting of the
      administration of necrogenic dose of carbontetrachloride to 2-acetaminofluorene
      pretreated rats (AAF/CCl4) or a large necrogenic dose of diethylnitrosamine
      (DEN). The oval cells expanded faster and the foci evolved earlier after repeated
      injury in the livers with preexistent parenchymal ductules. When the animals were
      left to survive for one more year increased liver tumor formation was observed
      exclusively in the DEN treated rats. Thus, repeated oval cell reactions are not
      necessarily carcinogenic. We conclude that the expansion of hepatic stem cell
      compartment conceptually can be used to facilitate liver regeneration without an
      increased risk of tumorigenesis. 

PMID- 23952743
TI  - Stealth polymeric vesicles via metal-free click coupling.
AB  - The strain-promoted azide-alkyne cycloaddition represents an optimal metal-free
      method for the modular coupling of amphiphilic polymer blocks. Hydrophilic
      poly(oxazoline) (PMOXA) or poly(ethylene glycol) (PEG) A-blocks were coupled with
      a hydrophobic poly(siloxane) B-block to provide triblock copolymers capable of
      self-assembling into vesicular nanostructures. Stealth properties investigated
      via a complement activation assay revealed the superior in vitro stealth
      attributes of polymeric vesicles synthesized via a metal-free approach to those
      coupled via the widely used copper-catalyzed click method. Furthermore, the
      ability to change a single parameter, such as the hydrophilic block, allowed the
      direct comparison of the biocompatibility properties of triblock copolymers
      containing PMOXA or PEG. Our studies convincingly demonstrate the need for a
      metal-free approach, both in preventing cytotoxicity while imparting optimal
      stealth properties for potential biomedical applications. 

PMID- 23952744
TI  - New insights into cell cycle and DNA damage response machineries through high
      resolution AMICO quantitative imaging cytometry.
AB  - OBJECTIVE: Progress in biology and medicine research is being driven by
      development of new instrumentation and associated methodologies which open
      analytical capabilities that expand understanding of complexity of biological
      systems. Application of cytometry, which is now widely used in so many
      disciplines of biology, is the best example of such a progress. METHODOLOGY:
      Recent publications push the envelope in expanding capabilities of cytometry by
      introducing a high resolution imaging cytometry defined as Automated Microscopy
      for Image CytOmetry (AMICO). This instrumentation is utilized to further
      elucidate mechanisms of the cell cycle progression and also the DNA damage
      response. This approach is going beyond the presently possible analytical
      technologies regarding throughput and depth of information. CONCLUSIONS: The
      possibility of multiparametric analysis combined with the high resolution mapping
      of individual constituents of cell cycle and DNA damage response machineries
      provides new tools to probe molecular mechanism of these processes. The
      capability of analysis of proximity of these constituents to each other offered
      by AMICO is a novel and potentially important approach that can be used to
      elucidate mechanisms of other biological processes.

PMID- 23952745
TI  - Relative respiratory syncytial virus cytopathogenesis in upper and lower
      respiratory tract epithelium.
AB  - RATIONALE: Respiratory syncytial virus (RSV) is a major pathogen that primarily
      infects airway epithelium. Most infants suffer mild upper respiratory tract (URT)
      symptoms, whereas approximately one-third progress to lower respiratory tract
      (LRT) involvement. Despite the ubiquity of URT infection, little is known about
      the relative cytopathogenesis of RSV infection in infant URT and LRT. OBJECTIVES:
      This study aimed to compare RSV cytopathogenesis in nasal- and bronchial-derived
      epithelium from the same individuals using novel models derived from well
      differentiated primary pediatric nasal (WD-PNECs) and bronchial epithelial cells
      (WD-PBECs). METHODS: WD-PNECs and WD-PBECs were generated from nasal and
      bronchial brushes, respectively, and mock-infected or infected with RSV BT2a. RSV
      tropism, infectivity, cytopathology, growth kinetics, cell sloughing, apoptosis,
      and cytokine and chemokine responses were determined. MEASUREMENTS AND MAIN
      RESULTS: RSV infection in both cultures was restricted to apical ciliated cells
      and occasional nonciliated cells but not goblet cells. It did not cause gross
      cytopathology. Infection resulted in apical release of progeny virus, increased
      apical cell sloughing, apoptosis, and occasional syncytia. RSV growth kinetics
      and peak titers were higher in WD-PBECs, coincident with higher ciliated cell
      contents, cell sloughing, and slightly compromised tight junctions. However,
      proinflammatory chemokine responses were similar for both cultures. Also, lambda
      IFNs, especially IL-29, were induced by RSV infection. CONCLUSIONS: RSV induced
      remarkably similar, albeit quantitatively lower, cytopathogenesis and
      proinflammatory responses in WD-PNECs compared with WD-PBECs that reproduce many
      hallmarks of RSV pathogenesis in infants. WD-PNECs may provide an authentic
      surrogate model with which to study RSV cytopathogenesis in infant airway
      epithelium.

PMID- 23952746
TI  - A comparative study of bivalirudin plus clopidogrel versus bivalirudin plus
      prasugrel in primary angioplasty using propensity score matching.
AB  - INTRODUCTION AND OBJECTIVES: In primary angioplasty, bivalirudin is superior to
      treatment with heparin plus glycoprotein inhibitors for reducing cardiovascular
      events, although bivalirudin increases the risk of stent thrombosis. Our
      hypothesis is that the use of prasugrel plus bivalirudin in primary angioplasty
      would reduce stent thrombosis and cardiovascular events. METHOD: Consecutive
      patients with acute ST-segment elevation myocardial infarction who were treated
      by primary angioplasty within 12 hours of the onset of symptoms received
      bivalirudin plus clopidogrel (Group A) or bivalirudin plus prasugrel (Group B).
      We compared the groups using propensity score matching. The combined end-point
      was cardiac death, thrombosis, acute myocardial infarction, and cerebrovascular
      accident at 30 days. RESULTS: We assessed 168 patients. The approach was
      preferentially radial (95.7%). No differences in baseline characteristics were
      observed between Groups A (n = 70) and B (n = 70). The total mortality and rate
      of major bleeding complications at 30 days were 0% for both of the groups. The
      rate of acute and subacute thrombosis was 4.3% in Group A and 0% in Group B (P =
      0.08). We observed an increased rate of events in Group A (5.7%) versus Group B
      (0%) (P = 0.042). CONCLUSIONS: The administration of bivalirudin plus prasugrel
      in primary percutaneous coronary intervention reduces cardiovascular effects
      compared to bivalirudin plus clopidogrel without increasing major bleeding
      complications during the first 30 days following primary angioplasty performed
      with a preferentially radial approach.

PMID- 23952747
TI  - 'It's about me'--a narrative analysis of female smokers with chronic obstructive
      pulmonary disease (COPD) and their relationship to smoking.
AB  - BACKGROUND: Chronic obstructive lung disease is a disease that is common among
      the smoking population. In Sweden, more women than men are smokers. The most
      effective treatment to improve the symptoms of COPD is to quit smoking but still
      many women continue to smoke, despite their illness. AIM: The aim of this study
      was to describe how a group of smoking women with chronic obstructive lung
      disease (COPD) experienced their everyday life and their relationship to smoking.
      METHOD: A qualitative study based on narratives from six women with COPD was
      conducted. The narratives focused on the women's everyday life and their
      relationship to smoking. The interviews were analysed into four themes and a new
      story, based on these themes were constructed. FINDINGS: The new story describes
      a woman with COPD that knows what she must do but cannot find the power within
      herself to take action. She talks about herself like a young bird that is going
      fly for the first time. CONCLUSION: The study indicates that these women need
      some form of individual help to find the inner strength that they lack. Their
      self-respect as well as their self-image needs to be boosted in order to
      strengthen their belief that they are going to cope without the cigarette.

PMID- 23952748
TI  - Molecular cloning and functional analysis of serotonin N-acetyltransferase from
      the cyanobacterium Synechocystis sp. PCC 6803.
AB  - Serotonin N-acetyltransferase (SNAT) catalyzes conversion of serotonin into N
      acetylserotonin, which is a direct precursor for melatonin biosynthesis in all
      organisms. Molecular cloning of plant SNAT from rice led to a screening for SNAT
      homolog genes in other species. We identified a cyanobacterium SNAT-like gene
      (cSNAT) that showed 56% amino acid homology with the rice SNAT. To confirm
      whether cSNAT encoded SNAT enzyme activity, we expressed cSNAT DNA in Escherichia
      coli and purified the cSNAT protein as a C-terminal His-tagged form. The purified
      cSNAT protein exhibited SNAT enzyme activities, transferring the acetyl group
      into either serotonin or tryptamine substrates. The optimum temperature was 55
      degrees C, but it was still highly active at 70 degrees C, suggesting that cSNAT
      is a thermotolerant enzyme. The Km and Vmax were 823 MUm and 1.6 nmol/min/mg
      protein, respectively. The cSNAT gene is highly conserved in all cyanobacterial
      taxa and seems to be an origin of SNAT in higher plants. The thermotolerance of
      cSNAT suggests that melatonin plays a role in the response to high-temperature
      stress. Further analysis of this role of melatonin in higher plants is needed. 

PMID- 23952749
TI  - Effect of stereotactic radiosurgery before bilateral adrenalectomy for Cushing's
      disease on the incidence of Nelson's syndrome.
AB  - OBJECT: Nelson's syndrome (NS) is a significant and frequent risk for patients
      with Cushing's disease (CD) who undergo bilateral adrenalectomy. A recent study
      has shown tumor progression in 47% of patients at risk for NS. The authors sought
      to define the rate of NS in patients who were treated with Gamma Knife
      stereotactic radiosurgery (GK SRS) prior to bilateral adrenalectomy. METHODS:
      Consecutive patients with CD who were treated with GK SRS after pituitary surgery
      but before bilateral adrenalectomy were included. Serial MRI sequences were
      analyzed to evaluate for pituitary tumor growth. Clinical evaluations were
      performed to screen for NS. Follow-up for adrenocorticotropic hormone levels and
      hormone studies of other pituitary axes was performed. RESULTS: Twenty
      consecutive patients were followed with neuroimaging and clinically for a median
      of 5.4 years (range 0.6-12 years). One patient (5%) developed pituitary tumor
      growth consistent with NS 9 months after adrenalectomy. By Kaplan-Meier analysis,
      progression-free survival was 94.7% at 1, 3, and 7 years. No predisposing factors
      were identified for the tumor progression. Two patients developed new pituitary
      dysfunction and no patient developed cranial neuropathy or visual deficit after
      GK SRS. CONCLUSIONS: These findings suggest that GK SRS not only serves a role as
      second-line therapy for CD, but that it also provides prophylaxis for NS when
      used before bilateral adrenalectomy.

PMID- 23952751
TI  - Erratum note.

PMID- 23952750
TI  - Introduction of Steven A. Nadler, recipient of the Henry Baldwin Ward medal for
      2013.

PMID- 23952752
TI  - Effect of evaluative others upon learning and performance of a complex motor
      task.
AB  - Two experiments were conducted to assess the effect of evaluation potential upon
      learning and performing a complex motor task. In Experiment 1, 45 subjects
      learned the motor task (mirror tracing) to criterion and were then introduced to
      one of three treatments. Subjects performed the task either (a) alone, (b) in the
      presence of a blindfolded audience, or (c) in the presence of an evaluative
      audience. In Experiment 2, 45 subjects were introduced to the same three
      treatments but the subjects did not learn the task beforehand. The subjects
      learning the motor task were significantly inhibited by the evaluative audience,
      while the subjects who had already learned the task were significantly
      facilitated in their motor responses. The blindfolded audience also had an effect
      upon learning and performance. The results of both experiments were discussed in
      relation to their support of Cottrell's evaluation potential hypothesis. 

PMID- 23952754
TI  - Lack of proactive inhibition in a psychomotor task at two retention intervals.
AB  - One form of the Tsai-Partington numbers test was given for 0, 1, 8, or 19
      original learning trials, and a different form was given for 10 transfer learning
      trials. Retention of transfer learning was tested after 24 hr for half of the
      subjects and after 2 min and again after 24 hr for the remainder of the subjects.
      Amount of forgetting of transfer learning increased with the length of the
      retention interval, but was not affected by the number of original learning
      trials; i.e., no proactive inhibition was observed. Also, performance during the
      transfer phase of the experiment was not significantly related to the number of
      original learning trials; no transfer was demonstrated. A previous study had
      found substantial retroactive inhibition with this task. 

PMID- 23952753
TI  - The use of location and distance in reproducing different amplitudes of movement.
AB  - Experiments have demonstrated that in order to reproduce a standard movement,
      subjects can move for a certain distance or move to a certain location. Available
      evidence tentatively suggests the use of distance for short movements and
      location for long movements. However, this evidence is in conflict with the motor
      short-term memory characteristics of short and long movements. An experiment is
      reported which demonstrates that subjects spontaneously use distance for short
      movements and location for long movements, the procedure adopted being to shift
      by small amounts the starting-point of the estimation movements and test for a
      consequent shift in the end-point of the estimation. The experiment also revealed
      that using distance or location to reproduce a 40 degrees  movement resulted in
      equal accuracy, suggesting that the use of large amplitudes of movement has
      caused previous investigators to find that distance is less accurate than
      location. 

PMID- 23952755
TI  - Transfer of training as a function of target speed in pursuit-rotor performance.
AB  - Transfer of training along the difficulty dimension was studied in the rotary
      pursuit situation using a modified proactive-retroactive inhibition experimental
      design. Difficulty was varied by changing speed of rotation. Two speeds were
      used: 55 RPM and 60 RPM. Greater than 100% transfer was obtained in cases where
      training was given at 55 RPM and the final test was at 60 RPM. The pattern of
      training of 55/60/60 (slow to fast) proved superior in the final test to the
      pattern 60/55/60 (fast to slow) even though the amount of training at the two
      speeds was the same for the two conditions. 

PMID- 23952756
TI  - Smoking and work load.
AB  - Smokers, smokers deprived, and nonsmokers performed a compensatory tracking task
      while simultaneously performing a crossadaptive loading task. By means of the
      cross-adaptive technique, the size of the subject's total work load (tracking and
      loading tasks combined) was individually tailored to utilize each subject's
      entire attentional capacity. No differences were detected as a function of
      smoking condition either in tracking or loading task performance, and it was
      concluded that smoking condition did not affect the size of the work load which
      could be handled. Performance generally improved with trials, however, none of
      the smoking condition * trials interactions was significant, indicating that
      performance changes with practice did not differ among the various smoking
      conditions. 

PMID- 23952757
TI  - The relationship of emotionality and worry components of anxiety to motor skills
      performance.
AB  - Three studies investigating the relationship between components of evaluation
      anxiety and typing performance are reported. Subjects represented business
      college students enrolled in typing (N=49) and English (N = 39) classes,
      applicants for clerical positions (N=50), and college students (N=11). State
      trait anxiety inventory A-trait scores (Study I only) and scores on a 10-item
      questionnaire designed to assess both the cognitive (worry) and emotional
      components of state anxiety were correlated with performance measures reflecting
      both typing speed and accuracy. Contrary to expectations, self-reported
      physiological and affective arousal (emotionality) was consistently shown to have
      little debilitative effect on performance. This finding was consistent across
      groups differing in degree of typing skill and across situations differing in
      amount of anxiety induced. Rather, worry scores were correlated negatively with
      performance as in studies of other types of academic performance. 

PMID- 23952758
TI  - Effects of training on endurance in hanging by the hands.
AB  - The effect of training on endurance in hanging by the hands from a horizontal bar
      was examined by timing the duration of such hanging in six male and five female
      subjects each weekday for 2 weeks. A significant increase in endurance was
      observed. The results, both subjective and objective, indicated the most
      important factors in the training to be increased psychological endurance of
      discomfort and increased muscular strength and efficiency. 

PMID- 23952759
TI  - Reactive inhibition and postrest performance in continuous inverted-reversed
      printing.
AB  - Subjects were given continuous practice printing upside down and backward the
      letters of the alphabet for 4 min, followed by a variable rest interval (0, .5,
      1, 2, 4, or 8 min), and then a final 2 min of practice. The amount of
      reminiscence was found to be a monotonically increasing function of the length of
      rest, and the initial negative slope of the postrest performance curve was
      nonmonotonically related to the length of rest. The results were interpreted in
      terms of a reactive inhibition model. 

PMID- 23952760
TI  - The instructional variable and kinesthetic cue recall.
AB  - The effect of learning instructions on immediate recall of kinesthetic distance
      and location-cue information was examined using a short-term motor retention
      paradigm. Three types of pre-movement learning instructions (distance, location,
      and distance plus location) were combined factorially with two types of post
      movement recall instructions (distance or location). Learning instructions
      indicated the cue or cues to be learned, while recall instructions indicated the
      cue to be recalled. Equivalent immediate recall of distance and location was
      found when learning instructions contained the cue recalled. In addition,
      superior immediate recall was observed for cues indicated during learning
      instructions. The results were interpreted as supporting the involvement of
      attentional processes in the learning of kinesthetic information associated with
      movement execution. 

PMID- 23952761
TI  - Comment on "retention characteristics of motor short-term memory cues".
AB  - Marteniuk (1973) used negative results, which may be attributed to a lack of
      power, to question the adequacy of variable error as a measure of forgetting. He
      also used these negative results, along with constant error results which were
      consistent with the Laabs (1971, 1973) model of motor memory, to reject parts of
      the model related to variable error. Caution is advised when interpreting
      negative results and interchanging dependent measures. 

PMID- 23952762
TI  - Further considerations of "retention characteristics of motor short-term memory
      cues".
AB  - Laabs (1975) has argued that Marteniuk's (1973) negative findings in opposition
      to his (1973) model can be explained by a lack of power. While statistical power
      was low, Marteniuk's results, and those of Jones (1974) as well, demonstrated a
      very small difference that was contrary to one of Laabs' predictions. It can be
      concluded this difference was not practically meaningful, suggesting that the
      Laabs (1973) model may have to be modified. 

PMID- 23952763
TI  - To exclude or not to exclude: further examination of the influence of white
      matter hyperintensities in diffusion tensor imaging research.
AB  - White matter hyperintensities (WMHIs) visible on magnetic resonance imaging (MRI)
      are common in both healthy adults and in those with medical or psychiatric
      problems. A practical methodological issue for diffusion tensor imaging (DTI)
      researchers is whether to include, or exclude, participants from a control group
      who have WMHIs. The aim of this study was to compare the influence of WMHIs on
      whole-brain DTI in trauma control subjects. Participants were 48 patients (no
      WMHIs, n=36; 2+WMHIs, n=12) prospectively recruited from the Emergency Department
      of Vancouver General Hospital (British Columbia, Canada). Participants completed
      an MRI brain scan at 6-8 weeks postinjury (mean, 47.3 days; standard deviation
      [SD], 6.2; range, 39-66). DTI was used to examine the integrity of white matter
      (WM) in 50 regions of the brain using measures of fractional anisotropy (FA), and
      mean (MD), radial (RD), and axial (AD) diffusivity. FA values that were >2 SDs
      below the mean, and MD, RD, and AD values that were >2 SDs above the mean, were
      classified as "abnormal scores" indicative of reduced WM integrity. In the entire
      sample, the 2+WMHI group had a greater number of abnormal FA, MD, and RD scores,
      compared to the no-WMHI group (p<0.015 and Cohen's d >0.82, indicating large to
      very large effect sizes, for all comparisons). When controlling for the effects
      of age using a matched-groups design, the 2+WMHI group still had a significantly
      greater number of abnormal FA, MD, and RD scores, compared to the no-WMHI group
      (all p<0.012, all d >0.89, large to very large effect sizes). Researchers should
      be aware that the inclusion or exclusion of subjects with incidental WMHIs will
      influence the results of DTI studies.

PMID- 23952764
TI  - Why do nurses change jobs? An empirical study on determinants of specific nurses'
      post-exit destinations.
AB  - AIM: The aims of this paper are, first, to identify the determinants of the
      'intention to leave' of nurses working at a general hospital, and, second, to
      provide recommendations for various stakeholders targeting prevention of
      premature leaving to various post-exit destinations. BACKGROUND: Nurse turnover
      is a serious problem, especially given the increased need for professional
      medical care because of demographic changes, and puts severe pressure on health
      care management staff. In order to meet future requirements for nursing staff, it
      is of utmost importance to empirically study their intention to leave either
      their department or hospital, and to identify the determinants of these various
      intentions to leave. METHOD: A cross-sectional survey was completed by 318 nurses
      working at various departments at a general hospital in Eindhoven, the
      Netherlands. Data were collected in May 2011. Using binary regression analysis,
      various determinants of nurses' reported post-exit career choices could be
      identified. CONCLUSION: Nurses' intention to leave is determined by their general
      satisfaction with management and leadership quality, their satisfaction with pay
      and benefits, their job satisfaction and work-to-home interference issues they
      have to deal with, but not by career development opportunities. IMPLICATIONS FOR
      NURSING MANAGEMENT: Preventing nurses from leaving their department or hospital
      requires careful attention from management and human resources professionals
      working in hospitals. In particular, the line managers who actually supervise
      nurses on a daily basis are key in ensuring that nurses are satisfied with their
      management and with the rewards they receive, and are able to cope with work-home
      interference.

PMID- 23952765
TI  - Nanoparticle-mediated delivery of oligonucleotides to the blood-brain barrier: in
      vitro and in situ brain perfusion studies on the uptake mechanisms.
AB  - Except for the few exceptions where topical administration is feasible, progress
      towards broad clinical application of nucleic acid therapeutics requires
      development of effective systemic delivery strategies. The central nervous system
      represents a particularly difficult organ for systemic delivery due to the blood
      brain barrier. We previously reported a nanoparticulate delivery system for
      targeted brain delivery of oligonucleotides upon systemic administration, i.e.
      liposome-encapsulated polyethylenimine/oligonucleotides polyplexes. In this
      study, cellular uptake and intracellular trafficking of the nanoparticles were
      further investigated using in situ brain perfusion technique followed by
      colocalization and fluorescence resonance energy transfer techniques. The brain
      endothelial uptake and possibly parenchymal accumulation were readily visualized
      upon administration via internal carotid artery perfusion. The nanoparticles were
      colocalized with early-endosome antigen, which confirms the brain endothelial
      uptake through transferrin receptor-mediated endocytosis. Fluorescence resonance
      energy transfer analysis also suggested the nanoparticles entered the brain
      endothelial cells while maintaining their integrity. Together, the enhanced brain
      uptake, as claimed previously, of the antibody-targeted nanoparticles was clearly
      confirmed with more convincing evidences. In addition, the experimental
      techniques described here should be applicable to the studies involving
      nanoparticle-mediated brain delivery of nucleic acid therapeutics.

PMID- 23952766
TI  - Transfer of airway skills from manikin training to patient: success of
      ventilation with facemask or LMA-Supreme(TM) by medical students.
AB  - During emergency care, the ability to ventilate the patient's lungs is a crucial
      skill. Supraglottic airway devices have an established role in emergency care,
      and manikin trials have shown that placement is easy even for inexperienced
      users. However, there is current discussion as to what extent these results can
      be transferred to patients. We studied the transfer of skills learnt on a manikin
      to the clinical situation in novice medical students during their anaesthesia
      rotation. They were required to ventilate the lungs of a manikin using a facemask
      and then position a supraglottic airway device (LMA-SupremeTM) and ventilate the
      lungs. This process was then repeated on anaesthetised patients, with standard
      ventilator settings to assess adequacy of ventilation. Sixty-three students
      participated in the manikin study. The success rate for ventilating the lungs was
      100% for both devices, but the mean (SD) time to achieve successful ventilation
      was 27.8 (24.4) s with the facemask compared with 38.6 (22.0) s with the LMA
      Supreme (p = 0.008). Fifty-one of the students progressed to the second part of
      the study. In anaesthetised patients, the success rate for ventilating the lungs
      was lower for the facemask, 27/41 (66%) compared with the LMA-Supreme 37/41 (90%,
      p = 0.006). For 26 students who succeeded with both devices, the tidal volume was
      lower using the facemask, 431 (192) ml compared with the LMA-Supreme 751 (221) ml
      (p = 0.001), but the time to successful ventilation did not differ, 60.0 (26.2) s
      vs 57.3 (26.6) s (p = 0.71). We conclude that the results obtained in manikin
      studies cannot be transferred directly to the clinical situation and that
      guidelines should take this into account. Based on our findings, a supraglottic
      airway device may be preferable to a facemask as the first choice for
      inexperienced emergency caregivers.

PMID- 23952767
TI  - Fractional crystallization and homogeneous nucleation of confined PEG
      microdomains in PBS-PEG multiblock copolymers.
AB  - Fractional crystallization, homogeneous nucleation of poly(ethylene glycol) (PEG)
      segment, and self-nucleation behavior of PEG segment within miscible double
      crystalline poly(butylene succinate)-poly(ethylene glycol) (PBSEG) multiblock
      copolymers with different composition and segment chain length were studied by
      differential scanning calorimetry (DSC). Surface morphology of PBSEG10K with
      different PEG content was investigated by atomic force microscope (AFM).
      Different from di- or triblock copolymers, the microstructure and confinement of
      PEG dispersed phase in PBS matrix phase highly depends on chain length and
      sequence as well as segment content. The transition point of the PEG segment
      content from heterogeneous to homogeneous nucleation mechanism decreased from 50
      to 39 wt % with PEG segment chain length increasing from 1000 to 2000 g/mol. When
      PEG segment chain length increased further to 6000 and 10000 g/mol, homogeneous
      nucleation phenomenon took place at much lower PEG content and fractional
      crystallization was observed at 29 and 24 wt %, respectively. Homogeneous
      nucleation mechanism of PBSEG(1K-36), PBSEG(2K-26), PBSEG(6K-19), and PBSEG(10K
      12) was evidenced by the large supercoolings needed for crystallization, as well
      as first-order crystallization kinetics obtained. Self-nucleation behaviors of
      PEG segment still rely on the composition of PBSEGs. In the case of heterogeneous
      nucleation crystallization, self-nucleation behaviors of PEG segment showed
      standard self-nucleation behavior with classical three self-nucleation domains.
      When the crystallizable chains were confined into isolated microdomains, however,
      self-nucleation domain (domain II) disappeared. The absence of III(A) was
      observed in PBSEG(2K-39), while PBSEG(6K-29) had both III(A) and III(SA).
      Furthermore, AFM morphology studies still indicated the confined degree of PEG
      segment by previous PBS crystals was profoundly influenced by segment fraction.
      The confinement of the PEG segment by previous PBS edge-on lamellae was observed
      in the sample which displays a homogeneous nucleation crystallization behavior.

PMID- 23952768
TI  - Community structures of N2 -fixing bacteria associated with the phyllosphere of a
      Holm oak forest and their response to drought.
AB  - Biological nitrogen (N) fixation is a key pathway in terrestrial ecosystems and
      is therefore critical for understanding the responses of ecosystems to global
      environmental changes. The free-living diazotrophic community is distributed
      along the canopy-to-soil profile, but the ecological significance of epiphyllic
      N2 fixers, despite their functional relevance, on plant foliar surfaces remains
      very poorly understood compared with the N2 -fixing community in forest litter
      and soils. We assessed the community structure of N2 fixers and overall bacteria
      by genetic fingerprinting (t-RFLP) to explore the seasonal successional patterns
      of the microbial community in the natural phyllosphere of a Holm oak (Quercus
      ilex) forest submitted to 12-year field experiment of rain exclusion mimicking
      the conditions of drought projected for the coming decades. Leaves of Holm oak
      were analysed in different seasons over a period of 1.5 years. The bacterial
      community of the phyllosphere did not correspond to the surrounding soil biome in
      the same area. These analyses provided field evidence for the presence of free
      living diazotrophs associated with the tissues of leaves of Holm oak, the
      dominant tree species of many Mediterranean forests. The results also revealed
      that the community composition is affected seasonally and inter-annually by the
      environment, and that the composition shifts in response to climate change.
      Drought treatment increased the richness of the epiphyllic microbial community,
      especially during the summer. These changes were associated with higher C:N
      ratios of leaves observed in response to drought in semiarid areas. This
      epiphyllic microbiota that can potentially fix N2 extends the capacity of plants
      to adapt to the environment.

PMID- 23952769
TI  - Goblet cell types in intestine of tiger barb and black tetra (Cyprinidae,
      Characidae: Teleostei).
AB  - Histochemical properties of goblet cells in intestine of a stomach-less teleost,
      tiger barb (Puntius tetrazona), and a stomach-containing teleost, black tetra
      (Gymnocorymbus ternetzi), are described and compared. The intestine goblet cells
      were mostly wide in both species, but in tiger barb, some of them were markedly
      thinner. In black tetra, all the intestine goblet cells displayed magenta colour
      after PAS, whereas in the tiger barb, only the thinner goblet cells displayed
      such affinity. The latter cell type was coloured strongly magenta when the tissue
      was treated with alcian blue (pH 2.5) followed by PAS, whereas the wide goblet
      cells in tiger barb and all goblet cells in black tetra displayed mainly a blue
      colour after such treatment. Further, the goblet cells in both species were
      coloured cleanly blue after high iron diamine followed by alcian blue (pH 2.5).
      The intestine goblet cells in both species displayed a moderate affinity to WGA
      and concanavalin A lectins and no affinity to DBA. Most of the goblet cells
      displayed no affinity to PNA, but some of them in the tiger barb displayed a
      moderate or strong affinity to this lectin. The affinity to WGA was somewhat
      strengthened after pre-treatment with neuraminidase. These results suggest that
      tiger barb contains two types or variants of intestinal goblet cells: high
      numbers of wide cells filled by acidic, non-sulphated mucin and some thinner
      cells filled by neutral mucin. The intestine goblet cells in black tetra were
      filled by variable amounts of neutral and acidic mucin, but the total number of
      such cells is much less than in tiger barb. The present lectin and neuraminidase
      results suggest that the intestinal mucins in both species contain significant
      amounts of N-acetylglucosamine, sialic acid and glucose/mannose, but seem to lack
      N-acetylgalactosamine. However, some of these cells in tiger barb contain
      moderate to large amounts of galactose. Together, these results suggest
      significant species-specific features of the intestine goblet cells and mucin
      types in tiger barb and black tetra. In conclusion, the present results suggest
      that the diet and feeding habits in stomach-less teleosts compared with stomach
      containing teleosts, greatly influence the number of intestine goblet cells and
      type of mucin in these cells. 

PMID- 23952770
TI  - Uncovering nurse educators' beliefs and values about grading academic papers:
      guidelines for best practices.
AB  - Fair and consistent assessment, specifically grading, is crucial to teaching and
      learning scholarship and is a professional responsibility of nurse educators.
      Yet, many would agree that assessment is one of the most challenging aspects of
      their role. Despite differing beliefs, values, and meanings attributed to grading
      and grades, teachers' grading practices should be guided by principles and
      supported by policies. Inconsistent grading practices among educators, students'
      unrealistic expectations of grades, and a trend toward grade inflation may be
      contributing to both educators' and students' concerns. A teaching scholarship
      project that led to a research study explored nurse educators' beliefs, values,
      and practices related to the grading of written academic work. The purpose of
      this article is to share the findings and the resulting grading guidelines that
      were developed to support nurse educators' endeavors to enact equitable grading
      practices.

PMID- 23952771
TI  - Comparison of Quality and Safety Education for Nurses (QSEN)-related student
      experiences during pediatric clinical and simulation rotations.
AB  - Nurse educators are challenged with providing meaningful clinical experiences for
      students. However, patient safety regulations constrain what nursing students are
      able to accomplish in the pediatric setting. So, what are students actually doing
      in their clinical rotation? This pilot observational study was undertaken to
      provide a snapshot of the experiences available to nursing students that develop
      the six Quality and Safety Education for Nurses (QSEN) competencies. Students
      were directly observed during pediatric clinical and pediatric simulation
      rotations, and their time-on-task was calculated and categorized. Three of the
      six QSEN competencies were observed more often than the others during both the
      simulation and clinical experiences. Much work needs to be done to include all
      QSEN-related knowledge and skills into prelicensure clinical rotations.

PMID- 23952772
TI  - Integrated learning through student goal development.
AB  - New strategies are emerging to promote structure and increase learning in the
      clinical setting. Nursing faculty designed a mechanism by which integrative
      learning and situated coaching could occur more readily in the clinical setting.
      The Clinical Goals Initiative was implemented for sophomore-, junior-, and senior
      level students in their clinical practicums. Students developed weekly goals
      reflecting three domains of professional nursing practice. Goals were shared with
      faculty and staff nurse mentors at the beginning of the clinical day to help
      guide students and mentors with planning for learning experiences. After 6 weeks,
      faculty and students were surveyed to evaluate project effectiveness. Faculty
      indicated that goal development facilitated clinical learning by providing more
      student engagement, direction, and focus. Students reported that goal development
      allowed them to optimize clinical learning opportunities and track their growth
      and progress. Faculty and students indicated the goals promoted student self
      learning, autonomy, and student communication with nurse mentors and faculty.

PMID- 23952773
TI  - Telling the story of role conflict among Black nurses and Black nursing students:
      a literature review.
AB  - Racism continues to affect minority nursing students and nurses in professional
      roles. A selective review of the literature published from 1992 to 2011 was
      conducted using the Cumulative Index of Literature in Nursing and Allied Health,
      ScienceDirect, and EBSCOhost. Keywords used included racism within nursing,
      minority nurses and role conflict, cultural diversity within nursing, racism, and
      diversity. The purpose of this review is to describe Black nurses' and Black
      nursing students' experiences of role conflict as an outcome of perceived racism
      within the nursing profession to gain an understanding of factors that contribute
      to perceived racism and role conflict. Noblit's and Hare's framework for
      metasynthesis of the data was used to identify and synthesize key concepts. The
      role perspectives of Hardy and Conway guided the review to develop a conceptual
      framework for minority role conflict and the nursing implications discussed
      herein.

PMID- 23952774
TI  - Creating innovative programs for the future.
AB  - Although several major national mandates advocate for a better educated
      workforce, this push comes at a time when the competition for faculty, financial
      resources, advanced technology, and students remains strong. If nurse educators
      are seriously considering creating a new nurse program at their school, some key
      points are essential during the development stage. Using the innovation
      frameworks from the Institute of Healthcare Improvement, from the global design
      firm IDEO, and from Gladwell's The Tipping Point: How Little Things Can Make a
      Big Difference, this article examines the informal, formal, internal, and
      external work needed during program conceptualization, initial program
      exploration, resource infrastructure, support, and evaluation for an effective
      and innovative plan.

PMID- 23952775
TI  - Integrating care of older adults into the nursing curriculum: a case exemplar
      project.
AB  - The growing number of older adults in the United States necessitates that nurses
      be prepared to care for this population. A case exemplar was created for use in a
      baccalaureate nursing program to prepare students for care of older adults in
      multiple settings, as well as to heighten interprofessional health care
      partnerships. The case exemplar follows the character, Mrs. Gates, in a scenario
      throughout the program. Another character, Mrs. Strokes, is introduced in a high
      fidelity laboratory simulation activity for more advanced students. The case
      scenario uses a team approach to care and includes activities that optimize
      critical thinking. This article describes the process of creating a case
      exemplar, including project pilot testing, and the potential for
      interprofessional education. The incorporation of case exemplars such as these
      can enhance the teaching-learning process, thereby improving care for older
      adults and their families.

PMID- 23952776
TI  - Comparison of student learning among three teaching methodologies in the
      pediatric clinical setting.
AB  - Facilitating effective clinical learning for pediatric nursing students is
      becoming increasingly challenging and limited in opportunities. Hospital leaders
      are concerned about the critical thinking and prioritization skills of new
      graduates and believe that inpatient clinical experiences are the only way to
      develop these skills. This study sought to compare the effectiveness of three
      different clinical teaching schedules in preparing nursing students to care for
      children and their families. Teaching methodology was randomly assigned to
      various amount of times in acute care inpatient settings. Student knowledge,
      clinical decision making, and student satisfaction and perception of learning
      were measured. No statistically significant differences among groups for either
      knowledge scores or clinical reasoning scores were noted. Student satisfaction
      results did not reveal differences among groups. Study findings will help
      educators to better plan clinical experiences and more effectively utilize an
      array of settings to optimize the clinical learning of pediatric nursing content.

PMID- 23952777
TI  - Early Indicators of NCLEX-RN performance.
AB  - Health Education Systems Incorporated (HESI(TM)) test results, course grades, and
      National Council Licensure Examination-Registered Nurse (NCLEX-RN((r))) outcomes
      of students in an associate degree nursing program at a midwestern public
      university were investigated. Statistical analysis revealed that introductory
      Fundamentals HESI test scores, more than either comprehensive HESI Exit Exam
      scores or other specialty HESI test scores, significantly predicted NCLEX-RN
      outcomes in this study (p < 0.05), while controlling for grade point average and
      high school percentile rank. In addition, of the general education courses and
      the nursing courses in the associate nursing program examined, Pediatric Nursing,
      Medical-Surgical Nursing, and Maternity Nursing course grades were found most
      statistically significantly influential of all the HESI test scores (p < 0.01).

PMID- 23952778
TI  - Psoriasis restricted to the nail in a 7-year-old child. Should biologics be an
      appropriate treatment modality when considering quality of life?

PMID- 23952779
TI  - Aggregatibacter actinomycetemcomitans biofilm killing by a targeted ciprofloxacin
      prodrug.
AB  - A pH-sensitive ciprofloxacin prodrug was synthesized and targeted against
      biofilms of the periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa).
      The dose required to reduce the viability of a mature biofilm of Aa by ~80% was
      in the range of ng cm(-2) of colonized area (mean biofilm density 2.33 * 10(9)
      cells cm(-2)). A mathematical model was formulated that predicts the temporal
      change in the concentration of ciprofloxacin in the Aa biofilm as the drug is
      released and diffuses into the bulk medium. The predictions of the model were
      consistent with the extent of killing obtained. The results demonstrate the
      feasibility of the strategy to induce mortality, and together with the
      mathematical model, provide the basis for design of targeted antimicrobial
      prodrugs for the topical treatment of oral infections such as periodontitis. The
      targeted prodrug approach offers the possibility of optimizing the dose of
      available antimicrobials in order to kill a chosen pathogen while leaving the
      commensal microbiota relatively undisturbed.

PMID- 23952780
TI  - Degradation of norgestrel by bacteria from activated sludge: comparison to
      progesterone.
AB  - Natural and synthetic progestagens in the environment have become a concern due
      to their adverse effects on aquatic organisms. Laboratory studies were performed
      to investigate aerobic biodegradation of norgestrel by bacteria from activated
      sludge in comparison with progesterone, and to identify their degradation
      products and biotransformation pathways. The degradation of norgestrel followed
      first order reaction kinetics (T1/2 = 12.5 d), while progesterone followed zero
      order reaction kinetics (T1/2 = 4.3 h). Four and eight degradation products were
      identified for norgestrel and progesterone, respectively. Six norgestrel
      degrading bacterial strains (Enterobacter ludwigii, Aeromonas hydrophila subsp.
      dhakensis, Pseudomonas monteilii, Comamonas testosteroni, Exiguobacterium
      acetylicum, and Chryseobacterium indologenes) and one progesterone-degrading
      bacterial strain (Comamonas testosteroni) were successfully isolated from the
      enrichment culture inoculated with aerobic activated sludge. To our best
      knowledge, this is the first report on the biodegradation products and degrading
      bacteria for norgestrel under aerobic conditions. 

PMID- 23952782
TI  - Carbanions in the gas phase.

PMID- 23952783
TI  - Three-dimensional mesoscale heterostructures of ZnO nanowire arrays epitaxially
      grown on CuGaO2 nanoplates as individual diodes.
AB  - We report a three-dimensional (3D) mesoscale heterostructure composed of one
      dimensional (1D) nanowire (NW) arrays epitaxially grown on two-dimensional (2D)
      nanoplates. Specifically, three facile syntheses are developed to assemble
      vertical ZnO NWs on CuGaO2 (CGO) nanoplates in mild aqueous solution conditions.
      The key to the successful 3D mesoscale integration is the preferential nucleation
      and heteroepitaxial growth of ZnO NWs on the CGO nanoplates. Using transmission
      electron microscopy, heteroepitaxy was found between the basal planes of CGO
      nanoplates and ZnO NWs, which are their respective (001) crystallographic planes,
      by the observation of a hexagonal Moire fringes pattern resulting from the slight
      mismatch between the c planes of ZnO and CGO. Careful analysis shows that this
      pattern can be described by a hexagonal supercell with a lattice parameter of
      almost exactly 11 and 12 times the a lattice constants for ZnO and CGO,
      respectively. The electrical properties of the individual CGO-ZnO mesoscale
      heterostructures were measured using a current-sensing atomic force microscopy
      setup to confirm the rectifying p-n diode behavior expected from the band
      alignment of p-type CGO and n-type ZnO wide band gap semiconductors. These 3D
      mesoscale heterostructures represent a new motif in nanoassembly for the
      integration of nanomaterials into functional devices with potential applications
      in electronics, photonics, and energy. 

PMID- 23952781
TI  - Human skin-derived stem cells as a novel cell source for in vitro hepatotoxicity
      screening of pharmaceuticals.
AB  - Human skin-derived precursors (hSKP) are postnatal stem cells with neural crest
      properties that reside in the dermis of human skin. These cells can be easily
      isolated from small (fore) skin segments and have the capacity to differentiate
      into multiple cell types. In this study, we show that upon exposure to
      hepatogenic growth factors and cytokines, hSKP acquire sufficient hepatic
      features that could make these cells suitable in vitro tools for hepatotoxicity
      screening of new chemical entities and already existing pharmaceutical compounds.
      Indeed, hepatic differentiated hSKP [hSKP-derived hepatic progenitor cells (hSKP
      HPC)] express hepatic progenitor cell markers (EPCAM, NCAM2, PROM1) and adult
      hepatocyte markers (ALB), as well as key biotransformation enzymes (CYP1B1, FMO1,
      GSTA4, GSTM3) and influx and efflux drug transporters (ABCC4, ABCA1, SLC2A5).
      Using a toxicogenomics approach, we could demonstrate that hSKP-HPC respond to
      acetaminophen exposure in a comparable way to primary human hepatocytes in
      culture. The toxicological responses "liver damage", "liver proliferation",
      "liver necrosis" and "liver steatosis" were found to be significantly enriched in
      both in vitro models. Also genes associated with either cytotoxic responses or
      induction of apoptosis (BCL2L11, FOS, HMOX1, TIMP3, and AHR) were commonly
      upregulated and might represent future molecular biomarkers for hepatotoxicity.
      In conclusion, our data gives a first indication that hSKP-HPC might represent a
      suitable preclinical model for in vitro screening of hepatotoxicity. To the best
      of our knowledge, this is the first report in which human postnatal stem cells
      derived from skin are described as a potentially relevant cell source for in
      vitro hepatotoxicity testing of pharmaceutical compounds. 

PMID- 23952784
TI  - Mycobacterium salmoniphilum infection in a farmed Russian sturgeon, Acipenser
      gueldenstaedtii (Brandt & Ratzeburg).

PMID- 23952785
TI  - Changes to CMS reimbursement rules for intraoperative neurophysiological
      monitoring: implications for telemedicine.
AB  - Intraoperative neurophysiological monitoring (IONM) is used as an adjunct for
      surgeries that pose risk to nervous system structures. IONM is performed by a
      technologist in the operating room and is overseen by a highly trained fellowship
      trained physician clinical neurophysiologist. Telemedicine has allowed the
      professional oversight component to be done remotely, with reimbursement for
      multiple simultaneous cases. Recent changes to Current Procedure Terminology
      coding and Medicare reimbursement policies provide options only for exclusive 1:1
      technologist:oversight physician billing. This policy change may create profound
      repercussions in the practice of telemedicine by actively discouraging the
      leveraging of highly specialized and scarce expertise through on-site physician
      extenders.

PMID- 23952787
TI  - Measurement of self-monitoring web technology acceptance and use in an e-health
      weight-loss trial.
AB  - BACKGROUND: Research on technology acceptance and use in e-health weight-loss
      interventions is limited. Using data from a randomized controlled trial of two e
      health interventions, we evaluated the acceptance and use of a self-monitoring
      Web site for weight loss. MATERIALS AND METHODS: We examined eight theoretical
      constructs about technology acceptance using adapted 5-point Likert scales and
      the association of measured Web site usage and weight loss. RESULTS: All scales
      had high internal consistency (Cronbach's alpha=0.74-0.97) in both interventions
      and at 3 and 15 months (end of intensive and maintenance intervention,
      respectively). From 3 to 15 months mean scores changed unfavorably for two
      constructs (compatibility and behavioral intention) among coach-led intervention
      participants, who received ongoing feedback on their self-monitoring entries.
      Among self-directed intervention participants, who received minimal coach
      support, mean scores changed unfavorably for five constructs (usefulness, ease of
      use, concern, compatibility, and behavioral intention). At 3 months, usefulness,
      ease of use, effect, compatibility, and behavioral intention in the coach-led
      group (Pearson r=0.33-0.5) and usefulness and affect in the self-directed group
      (r=0.43-0.46) were significantly correlated with Web site usage, which was
      correlated with weight loss (beta=-0.02, p<=0.001 for both interventions). From 3
      to 15 months, mean score changes for usefulness and behavioral intention
      correlated significantly with Web site usage in the coach-led group. CONCLUSIONS:
      The adapted acceptance measures showed acceptable psychometric properties and
      significant associations with actual Web site use, which correlated with weight
      loss. Better understanding of technology acceptance and use in e-health weight
      loss interventions may improve participant adherence and outcome.

PMID- 23952788
TI  - Test performance characteristics of quantitative nucleic acid testing for
      polyomaviruses in kidney and kidney-pancreas transplant recipients.
AB  - Screening for polyoma BK virus (BK) using nucleic testing (NAT) is recommended
      for kidney and kidney-pancreas transplant recipients, but the performance
      characteristics of quantitative BK NAT at different thresholds of plasma BK viral
      loads are unclear. We aim to evaluate the diagnostic accuracy of quantitative BK
      NAT as an add-on test to qualitative polyoma NAT for the diagnosis of BK virus
      associated nephropathy (BKVAN) in kidney and kidney transplant recipients. We
      calculated the test sensitivity, specificity, and predictive values at the
      different thresholds of plasma BK viral load for BKVAN. At the recommended
      threshold of >1 * 10(3) serum BK copies/mL serum for test positivity, the
      sensitivity for BKVAN was 92.9% (95% confidence intervals [CI]: 66.1-99.8) and
      specificity 79.1% (95%: CI 67.4-88.1), with corresponding positive and negative
      predictive values of 42.0% (95% CI: 24.8-57.7%) and 98.6% (95% CI: 98.3-99.9%),
      respectively. The overall area under curve for the quantitative BK NAT was 0.92
      (95% CI: 0.85-0.97). Quantitative BK NAT displays properties of high sensitivity
      and specificity that are fit for purpose as an add-on test to qualitative
      polyomavirus NAT for kidney and kidney-pancreas transplant recipients at risk of
      BKVAN.

PMID- 23952789
TI  - An inductive signalling network regulates mammalian tooth morphogenesis with
      implications for tooth regeneration.
AB  - Sequential and reciprocal epithelial-mesenchymal interactions, essential
      throughout such aspects of tooth morphogenesis as patterning, size and number of
      teeth, involves a well-ordered series of inductive and permissive signals that
      exert global control over cell proliferation, differentiation and organogenesis.
      In particular, growth factors, transcription factors and their corresponding
      receptors, as well as other soluble morphogens, make up a regulatory network at
      the molecular level that synergistically or antagonistically controls intra
      /inter-cellular signal transduction during odontogenesis. This review summarizes
      recent advances in the study of crucial signalling pathways, for example of BMPs,
      Wnt, Notch, Shh and FGF, with emphasis on the potential integrated signalling
      network responsible for tooth formation. Our work probes into the complexity of
      these inductive signalling pathways to promote the understanding of tooth
      regeneration. Additionally, our study provides further insights into therapeutic
      strategies for various dental abnormalities in patterning and number, such as
      tooth agenesis and supernumerary teeth. 

PMID- 23952790
TI  - Mammography utilization: patient characteristics and breast cancer stage at
      diagnosis.
AB  - OBJECTIVE: Missed mammograms represent missed opportunities for earlier breast
      cancer diagnosis. The purposes of this study were to identify patient
      characteristics associated with missed mammograms and to examine the association
      between missed mammograms and breast cancer stage at diagnosis. MATERIALS AND
      METHODS: Mammography frequency and cancer stage were retrospectively examined in
      1368 cases of primary breast cancer diagnosed at our clinic from 2002 to 2008.
      RESULTS: Regardless of age (median, 62.7 years), 1428 women who underwent
      mammography were more likely to have early-stage (stage 0-II) breast cancer at
      diagnosis than were those who did not undergo mammography (p < 0.001). Similarly,
      the number of mammographic examinations in the 5 years before diagnosis was
      inversely related to stage: 57.3% (94/164) of late-stage cancers were diagnosed
      in women missing their last five annual mammograms. In a multivariate analysis,
      family history of breast cancer was most predictive of undergoing mammography
      (odds ratio, 3.492; 95% CI, 2.616-4.662; p < 0.0001) followed by number of
      medical encounters (odds ratio, 1.022; 95% CI, 1.017-1.027; p < 0.0001). Time to
      travel to the nearest mammography center was also predictive of missing
      mammograms: Each additional minute of travel time decreased the odds of
      undergoing at least one mammographic examination in the 5 years before cancer
      diagnosis (odds ratio, 0.990; 95% CI, 0.986-0.993; p < 0.0001). CONCLUSION:
      Missing a mammogram, even in the year before a breast cancer diagnosis, increases
      the chance of a cancer diagnosis at a later stage. Interventions to encourage use
      of mammography may be of particular benefit to women most likely to miss
      mammograms, including those with no family history of breast cancer, fewer
      encounters with the health care system, and greater travel distance to the
      mammography center.

PMID- 23952791
TI  - An approximate transfer surface.
AB  - The principal defect in the Osgood (1949) transfer surface is the treatment of
      negative transfer. This may be corrected, although no surface can incorporate all
      the relevant transfer variables. The explanation and the scoring of negative
      transfer are discussed, with an emphasis on problems of skills learning. The
      conclusions reached are represented in the design of a new transfer surface. 

PMID- 23952792
TI  - Field dependence, displaced vision, and motor performance.
AB  - This study compared the effect of displaced lateral vision upon performance of a
      gross motor task in field-dependent and field-independent female athletes. No
      meaningful distinction in motor performance between the two groups of subjects
      was apparent during initial and final normal vision conditions. However, field
      independent subjects performed the criterion task with significantly greater
      accuracy during the displaced-vision condition. 

PMID- 23952793
TI  - Motor programming within a sequence of responses.
AB  - Choice reaction time prior to a motor response has been shown to depend on the
      nature of the response to be made. This effect is assumed to represent variations
      in programming time. However, as the length of a response sequence increases this
      effect becomes smaller, suggesting that some response programming is postponed
      until after the response sequence is initiated. The present experiment studied
      this assumed programming within a sequence of responses. For sequences comprised
      of two Morse Code responses (e.g. dit-dah) the initial reaction time was
      independent of the terminal response. However, programming of this terminal
      response was apparent as a lengthening of the duration of intervals within the
      response when the terminal response was dah rather than dit. When programming of
      parts of the sequence is postponed beyond the reaction time interval, the
      programming occurs later and influences the timing of the sequence of responses. 

PMID- 23952794
TI  - The latency of aiming movements.
AB  - The latency of movements requiring successively more and more precision was
      investigated in three simple reaction time experiments. The movements involved a
      horizontal arm sweep aimed at small circular targets. The results failed to
      provide strong support for the hypothesis that movements, and hence motor
      programs, requiring greater precision had longer latencies. The results are
      discussed in terms of a neural organization hypothesis, relating change in
      response complexity to the spatial and temporal structure of the motor program. 

PMID- 23952795
TI  - Boundary distance effects on overshooting.
AB  - Experiments with a subject-paced pursuit tracking task show that overshoot rate
      is dependent upon the distance between the target and the display boundary
      measured in the direction of movement, and that a previously noted inverse
      relationship with distance to the target is artifactual. The effect held for
      tasks with direct and reverse control-display relations, and for tasks with
      constant and variable target distances. The findings were consistent with
      Wetford's (1968) hypothesis that a pursuit response is initiated with a
      ballistic, distance-covering, movement. Ralph Leonardo carried out extensive work
      in collecting data, Fred Hyde maintained the apparatus, and Georgie Green
      assisted in data analysis. 

PMID- 23952796
TI  - What the eye tells the hand.
AB  - The information flow necessary to coordinate hand movements with vision is
      summarized. A series of experiments was performed which quantitatively examined
      and confirmed the summary. In general, an information-theoretic approach was
      used. It was confirmed that the speed and accuracy of hand movements are in a
      reciprocal relationship. The accuracy of a movement is more sensitive to a loss
      of visual information than the pacing mechanism. Both speed and accuracy are
      sensitive to withdrawal of information to maintain posture. It is suggested that
      the retrieval of a movement pre-program is disturbed by afferent "noise." The
      contribution of visual information to controlling standing posture, arm and
      shoulder movement, and wrist movement were investigated. 

PMID- 23952797
TI  - Efferent and afferent control of fast and slow arm movements.
AB  - The "outflow" hypothesis suggests that subjects can monitor the efferent activity
      effecting movements and can be aware of the course of movements independent of
      proprioception. To test the outflow hypothesis eight subjects were trained to
      make a simple arm movement and to subjectively estimate its extent. Following
      training, the extent of the movement was experimentally manipulated by
      introducing or omitting a small unperceived mechanical resistance, and subjective
      estimates of movement extent were evaluated. The presence of a shift in
      subjective movement extent would suggest a proprioceptive dependency, while the
      absense of a shift would suggest efference monitoring. Clear evidence for
      efference monitoring was not found, although subjective movement extent was found
      not to vary as would be expected from purely proprioceptive feedback monitoring
      suggesting other (possibly feedforward) mechanisms. 

PMID- 23952798
TI  - The serial maniuplation apparatus.
AB  - The etiology of the development of the Serial Manipulation Apparatus stems from a
      need in the science of motor skill acquisition to develop a form of task more
      nearly resembling the demands of real-life movement behaviors; namely, where
      cognition and perception play a major role in determining movement effectiveness.
      Also, a need was detected for a laboratory task that could be made sufficiently
      difficult to produce performance curves similar to those that might be obtained
      in real-life situations. 

PMID- 23952799
TI  - A new high-energy cathode for a Na-ion battery with ultrahigh stability.
AB  - Large-scale electric energy storage is a key enabler for the use of renewable
      energy. Recently, the room-temperature Na-ion battery has been rehighlighted as
      an alternative low-cost technology for this application. However, significant
      challenges such as energy density and long-term stability must be addressed.
      Herein, we introduce a novel cathode material, Na1.5VPO4.8F0.7, for Na-ion
      batteries. This new material provides an energy density of ~600 Wh kg(-1), the
      highest value among cathodes, originating from both the multielectron redox
      reaction (1.2 e(-) per formula unit) and the high potential (~3.8 V vs Na(+)/Na)
      of the tailored vanadium redox couple (V(3.8+)/V(5+)). Furthermore, an
      outstanding cycle life (~95% capacity retention for 100 cycles and ~84% for
      extended 500 cycles) could be achieved, which we attribute to the small volume
      change (2.9%) upon cycling, the smallest volume change among known Na
      intercalation cathodes. The open crystal framework with two-dimensional Na
      diffusional pathways leads to low activation barriers for Na diffusion, enabling
      excellent rate capability. We believe that this new material can bring the low
      cost room-temperature Na-ion battery a step closer to a sustainable large-scale
      energy storage system.

PMID- 23952800
TI  - Phase II clinical study on intraoperative photodynamic therapy with talaporfin
      sodium and semiconductor laser in patients with malignant brain tumors.
AB  - OBJECT: The objective of the present study was to perform a prospective
      evaluation of the potential efficacy and safety of intraoperative photodynamic
      therapy (PDT) using talaporfin sodium and irradiation using a 664-nm
      semiconductor laser in patients with primary malignant parenchymal brain tumors.
      METHODS: In 27 patients with suspected newly diagnosed or recurrent primary
      malignant parenchymal brain tumors, a single intravenous injection of talaporfin
      sodium (40 mg/m(2)) was administered 1 day before resection of the neoplasm. The
      next day after completion of the tumor removal, the residual lesion and/or
      resection cavity were irradiated using a 664-nm semiconductor laser with a
      radiation power density of 150 mW/cm(2) and a radiation energy density of 27
      J/cm(2). The procedure was performed 22-27 hours after drug administration. The
      study cohort included 22 patients with a histopathologically confirmed diagnosis
      of primary malignant parenchymal brain tumor. Thirteen of these neoplasms (59.1%)
      were newly diagnosed glioblastomas multiforme (GBM). RESULTS: Among all 22
      patients included in the study cohort, the 12-month overall survival (OS), 6
      month progression-free survival (PFS), and 6-month local PFS rates after surgery
      and PDT were 95.5%, 91%, and 91%, respectively. Among patients with newly
      diagnosed GBMs, all these parameters were 100%. Side effects on the skin, which
      could be attributable to the administration of talaporfin sodium, were noted in
      7.4% of patients and included rash (2 cases), blister (1 case), and erythema (1
      case). Skin photosensitivity test results were relatively mild and fully
      disappeared within 15 days after administration of photosensitizer in all
      patients. CONCLUSIONS: Intraoperative PDT using talaporfin sodium and a
      semiconductor laser may be considered as a potentially effective and sufficiently
      safe option for adjuvant management of primary malignant parenchymal brain
      tumors. The inclusion of intraoperative PDT in a combined treatment strategy may
      have a positive impact on OS and local tumor control, particularly in patients
      with newly diagnosed GBMs. Clinical trial registration no.: JMA-IIA00026
      (https://dbcentre3.jmacct.med.or.jp/jmactr/App/JMACTRS06/JMACTRS06.aspx?seqno=862
      .

PMID- 23952801
TI  - Reaching a turning point--how patients in forensic care describe trajectories of
      recovery.
AB  - In Sweden, the duration of treatment is increasing for patients admitted to
      forensic psychiatric care. To reduce the length of stay, it is important for the
      forensic rehabilitation and recovery process to be effective and safe. Not much
      is known about how the process of recovery and transition begins and how it is
      described by the forensic patients. The purpose of this study was to explore how
      forensic patients with a history of high risk for violence experienced the turn
      towards recovery. A qualitative content analysis was used to analyse interviews
      with 10 patients who had decreased their assessed risk for violence on the risk
      assessment instrument HCR-20 and who were successfully managed a lower level of
      security. Three themes were identified: (i) the high-risk phase: facing intense
      negative emotions and feelings (ii) the turning point phase: reflecting on and
      approaching oneself and life in a new way (iii) the recovery phase: recognising,
      accepting and maturing. In the high-risk phase, chaotic and overwhelming feelings
      were experienced. The turning point phase was experienced as a sensitive stage,
      and it was marked by being forced to find a new, constructive way of being. The
      recovery phase was characterised by recognising personal circumstances in life,
      including accepting the need for structure, a feeling of maturity and a sense of
      responsibility for their own life. In order to ensure a successful recovery, the
      forensic nursing staff needs to recognise and support processes related to
      treatment motivation and turning points. Recommendations for best nursing
      practice are given accordingly. 

PMID- 23952802
TI  - Examining the antecedents of engaged nurses in Italy: perceived organisational
      support (POS); satisfaction with training and development; discretionary power.
AB  - AIM: This paper used Social Exchange Theory to empirically examine whether
      perceived organisational support, satisfaction with training and development and
      perception of discretionary power are antecedents of engagement for registered
      nurses working in Italian public and private hospitals (n = 827). BACKGROUND:
      According to Social Exchange Theory, effective workplace relationships support
      employees and encourage nurses to use training to enhance their workplace
      outcomes. METHOD: This research used a cross-sectional design. Data were
      collected from registered nurses working in six Italian hospitals using a survey
      based, self-report strategy. RESULT: Regression analysis found that the variance
      of process-oriented supervision accounted for 6.9% of Italian registered nurse's
      perception of engagement, training and development accounted for 26.8% and
      discretionary power accounted for 2.1%. CONCLUSION: Workplace relationships
      enhance autonomy and engagement. Effective workplace relationship impacts
      positively on nurses' outcome. IMPLICATIONS FOR NURSING MANAGEMENT: This paper
      confirms the relevance of training to enhance engagement of nurses. It also
      confirms the importance of workplace relationships in enhancing autonomy and
      engagement. Previous research has identified the importance of nurses' autonomy
      in an environment where there are shortages of nurses. This study confirms a
      similar situation for Italian nurses. The findings underline the relevance of
      investments in continuous professional development to enhance nurses' engagement
      in private and public health-care settings.

PMID- 23952803
TI  - Detecting lesions after traumatic brain injury using susceptibility weighted
      imaging: a comparison with fluid-attenuated inversion recovery and correlation
      with clinical outcome.
AB  - The development and utilization of newer neuroimaging modalities provides the
      capability to more accurately detect the extent of pathology after TBI. The
      current study examined the ability of susceptibility-weighted imaging (SWI) to
      detect lesions after TBI as well as the relationship to subsequent clinical
      outcome. The performance of SWI was compared to that of fluid-attenuated
      inversion recovery (FLAIR). This study comprised 79 individuals with mild-to
      severe TBI, 38 of whom completed neuropsychological tests of attention, working
      memory, processing speed, memory, and executive functions. SWI was found to
      quantify a greater lesion volume over the entire brain, specifically in frontal,
      central, limbic, subcortical gray, and parietal brain regions, than did FLAIR.
      Moreover, SWI was able to identify TBI-related lesions in almost one third of
      patients for whom FLAIR was unable to detect any lesions. Greater overall SWI
      volume, as well as frontal SWI volume, was found to relate to the severity of
      TBI. Conversely, no association was found between FLAIR lesion volume and injury
      severity. In addition, there was some evidence that higher lesion volume, for
      both SWI and FLAIR, were associated with poorer memory as well as processing
      speed impairment. This study suggests that SWI may provide additional sensitivity
      in the detection of lesions after TBI. Consequently, this imaging sequence may
      provide a more accurate representation of the severity of individuals' injuries
      and their subsequent neuropsychological outcomes.

PMID- 23952804
TI  - Defining the transition zone of Hirschsprung disease.

PMID- 23952805
TI  - Virtual airway simulation to improve dexterity among novices performing
      fibreoptic intubation.
AB  - We developed a virtual reality software application (iLarynx) using built-in
      accelerometer properties of the iPhone((r)) or iPad((r)) (Apple Inc., Cupertino,
      CA, USA) that mimics hand movements for the performance of fibreoptic skills.
      Twenty novice medical students were randomly assigned to virtual airway training
      with the iLarynx software or no additional training. Eight out of the 10 subjects
      in the standard training group had at least one failed (> 120 s) attempt compared
      with two out of the 10 participants in the iLarynx group (p = 0.01). There were a
      total of 24 failed attempts in the standard training group and four in the
      iLarynx group (p < 0.005). Cusum analysis demonstrated continued group
      improvement in the iLarynx, but not in the standard training group. Virtual
      airway simulation using freely available software on a smartphone/tablet device
      improves dexterity among novices performing upper airway endoscopy.

PMID- 23952806
TI  - Three-dimensional reference interaction site model self-consistent field study of
      the electronic structure of [Cr(H2O)6]3+ in aqueous solution.
AB  - The three-dimensional reference interaction-site model self-consistent-field (3D
      RISM-SCF) method was applied to the electronic structure of hexahydrated chromium
      trication [Cr(H2O)6](3+) in aqueous solution. The 3D distribution around
      [Cr(H2O)6](3+) showed 12 maximum density points arising from hydrogen bonds, as
      well as eight local maximum points at the hollow sites, in the second hydration
      shell. The 3D distribution function also indicated 20 local maximum sites in the
      third hydration shell. The low-lying excited states of vertical transitions were
      computed using time-dependent density functional theory (TD-DFT), including the
      electric field from the solvent. The electronic configurations and excitation
      energies calculated using DFT and 3D-RISM-SCF were very similar, although the
      orbital energies involved in the transition were rather different. The two lowest
      excited states (1(4)T and 2(4)T) were roughly assigned to the d-d transitions,
      and the third and fourth excited states (3(4)T and 4(4)T) were assigned to ligand
      to-metal charge-transfer transitions. The computed excited energies were in good
      agreement with the experimental values. 

PMID- 23952807
TI  - In vivo release and retinal safety of intravitreal implants of thalidomide in
      rabbit eyes and antiangiogenic effect on the chorioallantoic membrane.
AB  - PURPOSE: To evaluate the in vivo release, retinal safety and antiangiogenic
      effect of a thalidomide-loaded poly-lactide-co-glycolide intravitreal implant.
      METHODS: New Zealand white rabbits, divided into two groups, I and II, received
      an intravitreal implant containing or not thalidomide, respectively (n = 12).
      Intravitreal drug levels were determined during a six-week study period. The
      potential for toxicity associated with the implants was evaluated by
      electroretinography and light microscopy (n = 8). Twelve chorioallantoic
      membranes (CAMs) from chicken eggs were incubated with thalidomide dispersion,
      implants containing or not thalidomide and vitreous samples and analyzed after
      two days regarding the percentage of vessels regression. RESULTS: Intravitreal
      concentrations of thalidomide (ng/ml) were 690.21 +/- 177.95, 372.51 +/- 185.56,
      240.59 +/- 133.48, 327.54 +/- 169.71, 294.26 +/- 142.41 and 465.18 +/- 157.51 at
      1, 2, 3, 4, 5 and 6 weeks, respectively, after implantation in group I rabbits.
      No drug was detected in group II samples. Electroretinography and histological
      evaluations did not show any sign of retina toxicity. There was significant
      regression of vessels in CAM incubated with thalidomide dispersion, thalidomide
      loaded implants and vitreous samples from group I when compared to control.
      CONCLUSION: The intravitreal implants delivered safe doses of thalidomide that
      were also effective to induce vessels regression in CAMs.

PMID- 23952808
TI  - T3 and cardiac myocyte cell: a theoretical model.
AB  - In the last decades, the outstanding role of Thyroid gland in regulating both
      physiological and pathological operation of cardiovascular system has been
      acknowledged worldwide. Three main domains of Thyroid function, that is to say,
      euthyroidism -hyperthyroidism-hypothyroidism, have a direct impact on cardiac
      response through a variety of mechanisms. Cellular pathways mediate in cardiac
      contractility, cardiac output, cardiac rhythm, arterial blood pressure and
      peripheral vessel resistance. Particular biochemical algorithms exist not only
      between Thyroid hormones' serum concentration and thyroid gland but also between
      the hormones' serum level and heart muscle genes. These biochemical pathways
      primarily regulate the appropriate secretion of levothyroxine (T4) and
      triiodothyronine(T3) via Thyroid- Stimulating-Hormone(TSH) pituitary system, and
      secondly adjust the cardiac function. In this study, a mathematic model has been
      developed describing significant aspects of positive or negative feedback
      mechanisms of THYRO-CARDIAC (THY-CAR) system along with potential applications of
      novel up-to-date patents in this area of research. 

PMID- 23952809
TI  - Antioxidant treatment and endothelial dysfunction: is it time for flavonoids?
AB  - Endothelial dysfunction represents an imbalance between vasodilatory and
      vasoconstrictory molecules secreted by endothelium. Oxidative stress is a major
      factor leading to endothelial dysfunction with significant prognostic
      implications for cardiovascular events. The generation of reactive oxygen species
      is strongly related to various oxidase enzymes such as xanthine oxidase,
      uncoupled endothelial nitric oxide synthase, cyclooxygenase, glucose oxidase,
      lipooxygenase, nicotinamide-adenine dinucleotide phosphate oxidase and to
      mitochondrial electron transport mechanisms. Several pharmaceutical agents exert
      effects beyond their principal role, such as anti-inflammatory and antioxidant,
      while the reports on antioxidant vitamins remain controversial especially those
      based on large scale studies. Moreover, there are studies on other agents already
      patented, but these are not well evaluated. Recently, there is growing interest
      in the role of dietary flavonoids and their potential to improve endothelial
      function by modifying oxidative stress status. Flavonoids are important
      components of 'functional foods', with beneficial effects on cardiovascular
      health, mainly due to their antioxidant activity. However, the vascular
      protective role of flavonoids and especially their antioxidant properties are
      still under investigation. 

PMID- 23952810
TI  - Melatonin reverses the decreases in hippocampal protein serine/threonine kinases
      observed in an animal model of autism.
AB  - Lower global cognitive function scores are a common symptom of autism spectrum
      disorders (ASDs). This study investigates the effects of melatonin on hippocampal
      serine/threonine kinase signaling in an experimental ASD model. We found that
      chronic melatonin (1.0 or 5.0 mg/kg/day, 28 days) treatment significantly rescued
      valproic acid (VPA, 600 mg/kg)-induced decreases in CaMKII (Thr286), NMDAR1
      (Ser896), and PKA (Thr197) phosphorylation in the hippocampus without affecting
      total protein levels. Compared with control rats, the immunostaining of pyramidal
      neurons in the hippocampus revealed a decrease in immunolabeling intensity for
      phospho-CaMKII (Thr286) in the hippocampus of VPA-treated rats, which was
      ameliorated by chronic melatonin treatment. Consistent with the elevation of
      CaMKII/PKA/PKC phosphorylation observed in melatonin-treated rat, long-term
      potentiation (LTP) was enhanced after chronic melatonin (5.0 mg/kg) treatment, as
      reflected by extracellular field potential slopes that increased from 56 to 60
      min (133.4 +/- 3.9% of the baseline, P < 0.01 versus VPA-treated rats) following
      high-frequency stimulation (HFS) in hippocampal slices. Accordingly, melatonin
      treatment also significantly improved social behavioral deficits at postnatal day
      50 in VPA-treated rats. Taken together, the increased phosphorylation of
      CaMKII/PKA/PKC signaling might contribute to the beneficial effects of melatonin
      on autism symptoms.

PMID- 23952811
TI  - Adolescents' attitudes about the role of mental illness in suicide, and their
      association with suicide risk.
AB  - We examined teenagers' attitudes about the role of mental illness in suicidal
      behavior and the relationship between these attitudes and suicide risk. Serious
      suicidal ideation or behavior and associated risk factors (gender, depression,
      substance problems, and first-hand experience with a suicidal peer) were assessed
      in 2,419 students at six New York high schools. Less than one fifth of students
      thought that mental illness was a major contributor to suicide. Suicidal
      adolescents and those at risk were less likely than their nonsuicidal and low
      risk counterparts to associate suicide with mental illness. Our findings
      contribute to the debate over whether accepting attitudes toward suicide increase
      suicide risk. 

PMID- 23952812
TI  - The overexpression of a maize mitogen-activated protein kinase gene (ZmMPK5)
      confers salt stress tolerance and induces defence responses in tobacco.
AB  - As sessile organisms, plants are exposed to potential dangers, including multiple
      biotic and abiotic stresses. The mitogen-activated protein kinase (MAPK) is a
      universal signalling pathways involved in these processes. A previous study
      showed that maize ZmMPK5 is induced by various stimuli at transcriptional and
      post-translational levels. In this study, ZmMPK5 was overexpressed in tobacco to
      further analyse its biological functions. Under salt and oxidative stresses,
      ZmMPK5-overexpressing lines displayed less severe damage and stronger growth
      phenotypes corresponding to a series of physiological changes. In addition, the
      transgenic lines accumulated less reactive oxygen species (ROS) and had higher
      levels of antioxidant enzyme activity and metabolites than wild-type (WT) plants
      following NaCl treatment. Quantitative RT-PCR revealed that the expression of ROS
      related and stress-responsive genes was higher in transgenic plants than in WT
      plants. Furthermore, transgenic lines exhibited enhanced resistance to viral
      pathogens, and expressed constitutively higher transcript levels of pathogenesis
      related genes, such as PR1a, PR4, PR5 and EREBP. Taken together, these results
      demonstrated that ZmMPK5 is involved in salt stress, oxidative stress and
      pathogen defence signalling pathways, and its function may be at least partly
      devoted to efficiently eliminating ROS accumulation under salt stress.

PMID- 23952813
TI  - "Amide resonance" in the catalysis of 1,2-alpha-L-fucosidase from Bifidobacterium
      bifidum.
AB  - Bifidobacterium is a genus of Gram-positive bacteria, which is important in the
      absorption of nourishment from the human milk oligosaccharides (HMO). We present
      here the detailed simulation of the enzymatic hydrolysis of 2'-fucosyllactose
      catalyzed by 1,2-alpha-L-fucosidase from Bifidobacterium bifidum using the
      combined quantum mechanical and molecular mechanical approach. Molecular dynamics
      simulations and free energy profiles support that the overall reaction is a
      stepwise mechanism. The first step is the proton transfer from N423 to D766, and
      the second step involves the hydrolysis reaction via the inversion mechanism
      catalyzed by the amide group of N423. Assisted by D766, N423 serves as the
      general base to activate the water molecule to attack the anomeric carbon center.
      E566 is the general acid to facilitate the cleavage of glycosidic bond between L
      fucose and galactose units. The intrinsic resonance structure for the side chain
      amide group of the asparagine residue is shown to be the origin to the catalytic
      activity, which is also confirmed by the mutagenesis simulation of N423G.

PMID- 23952814
TI  - Estimation of the acid dissociation constant of perfluoroalkyl carboxylic acids
      through an experimental investigation of their water-to-air transport.
AB  - The acid dissociation constants (pKas) of perfluoroalkyl carboxylic acids (PFCAs)
      have been the subject of discussion in the literature; for example, values from 
      0.2 to 3.8 have been suggested for perfluorooctanoic acid (PFOA). The dissociated
      anionic conjugate bases of PFCAs have negligible air-water partition coefficients
      (KAWs) and do not volatilize from water. The neutral acids, however, have
      relatively high KAWs and volatilization from water has been demonstrated. The
      extent of volatilization of PFCAs in the environment will depend on the water pH
      and their pKa. Knowledge of the pKas of PFCAs is therefore vital for
      understanding their environmental transport and fate. We investigated the water
      to-air transfer of PFCAs in a novel experimental setup. We used ~1 MUg L(-1) of
      PFCAs in water (above environmental background concentrations but below the
      concentration at which self-association occurs) at different water pH (pH 0.3 to
      pH 6.9) and sampled the PFCAs volatilized from water during a 2-day experiment.
      Our results suggest that the pKas of C4-11 PFCAs are <1.6. For PFOA, we derived a
      pKa of 0.5 from fitting the experimental measurements with a volatilization
      model. Perfluoroalkane sulfonic acids were not volatilized, suggesting that their
      pKas are below the investigated pH range (pKa <0.3). 

PMID- 23952815
TI  - Bleomycin-induced flagellate dermatitis: report of four paediatric cases.

PMID- 23952816
TI  - Efficacy of long scleral tunnel technique in preventing Ahmed glaucoma valve tube
      exposure through conjunctiva.
AB  - PURPOSE: To evaluate the efficacy of long scleral tunnel technique used in Ahmed
      glaucoma valve (AGV) implantation in preventing tube exposure through
      conjunctiva. MATERIALS AND METHODS: Patients of adult age, who were unresponsive
      to maximum medical treatment and underwent AGV implantation, were divided into
      two groups and investigated retrospectively. Group 1 consisted of 40 eyes of 38
      patients that underwent surgery by long scleral tunnel technique and Group 2
      consisted of 38 eyes of 35 patients that underwent implantation by processed
      pericardium patch graft method. RESULTS: The mean age was 54.8 +/- 14.6 years
      (range 26-68 years) and the mean follow-up duration was 46.7 +/- 19.4 months
      (range 18-76 months) for the patients in Group 1, whereas the mean age was 58.6
      +/- 16.7 years (range 32-74 years) and mean follow-up period was 43.6 +/- 15.7
      months (range 20-72 months) for the patients in Group 2 (p > 0.05). In the course
      of follow-up, tube exposure was detected in one (2.5%) eye in Group 1 and in
      three (7.9%) eyes in Group 2 (p = 0.042). CONCLUSION: Long scleral tunnel
      technique is beneficial in preventing conjunctival tube exposure in AGV
      implantation surgery.

PMID- 23952817
TI  - A rare case of Behcet's syndrome presenting with bilateral papillitis.
AB  - A previously healthy 28-year-old white man complained of acute headache and
      mildly blurred vision since a month earlier which did not respond to analgesics.
      Brain magnetic resonance imaging was normal. He did not agree to be admitted and
      nor to additional testing by a neurologist and did not respond to oral
      acetazolamide. At the next visit (a month later), the ophthalmic examination
      showed the best corrective vision of 7/10 in both eyes, and 2 + cell in the right
      eye anterior chamber. Except for leukocytosis and positive C reactive protein,
      other tests (including cerebrospinal pressure and composition and brain magnetic
      resonance angiography) were normal. The rheumathologist consultation revealed a
      history of Behcet in the patient and his brother and HLA B5 was positive. Optic
      disc swelling significantly decreased with interavenous stroid and the headache
      disappeared. Two weeks later, visual acuity reached 9/10 and papillitis resolved.

PMID- 23952818
TI  - The construction of a zwitterionic PVDF membrane surface to improve biofouling
      resistance.
AB  - Biofouling of membrane surfaces by the attachment of microorganisms is one of the
      major obstacles for ensuring the effectiveness of membrane separation processes.
      This work presents the construction of a zwitterionic PVDF membrane surface with
      improved resistance to biofouling. An amphiphilic copolymer of poly(vinylidene
      fluoride)-graft-poly(N,N-dimethylamino-2-ethylmethacrylate) (PVDF-g-PDMAEMA) was
      first synthesized via radical graft copolymerization and then the flat membrane
      was cast with immersed phase inversion. The PDMAEMA side chains tended to
      aggregate on the membrane surface, pore surface and internal pore channel
      surface, and were converted with 1,3-propane sultone (1,3-PS) to yield a
      zwitterionic membrane surface. A higher conversion of PDMAEMA chains and
      distribution of zwitterions were obtained using a longer treatment time. A
      biofouling assay indicated that incorporation of zwitterions suppressed the
      adsorption of extracellular polymer substances and the adhesion of Escherichia
      coli bacterial cells to the membrane surface, endowing the membrane with a high
      flux recovery and biofouling resistance in the filtration process.

PMID- 23952819
TI  - Mixed AggregAte (MAA): a single concept for all dipolar organometallic
      aggregates. 1. Structural data.

PMID- 23952820
TI  - Chronic streptococcosis in Nile tilapia, Oreochromis niloticus (L.), caused by
      Streptococcus agalactiae.

PMID- 23952821
TI  - Vaccine mandates are justifiable because we are all in this together.

PMID- 23952823
TI  - The value of sound research practices even facing pandemics.

PMID- 23952822
TI  - Ethics of clinical science in a public health emergency: drug discovery at the
      bedside.
AB  - Clinical research under the usual regulatory constraints may be difficult or even
      impossible in a public health emergency. Regulators must seek to strike a good
      balance in granting as wide therapeutic access to new drugs as possible at the
      same time as gathering sound evidence of safety and effectiveness. To inform
      current policy, I reexamine the philosophical rationale for restricting new
      medicines to clinical trials, at any stage and for any population of patients
      (which resides in the precautionary principle), to show that its objective to
      protect public health, now or in the future, could soon be defeated in a
      pandemic. Providing wider therapeutic access and coordinating observations and
      natural experiments, including service delivery by cluster (wedged cluster
      trials), may provide such a balance. However, there are important questions of
      fairness to resolve before any such research can proceed. 

PMID- 23952824
TI  - Is the precautionary principle adaptable to emergency scenarios to speed up
      research, risking the individual informed consent?

PMID- 23952825
TI  - A free-market approach to clinical data gathering is more ethical.

PMID- 23952826
TI  - Public health emergencies: research's friend or foe?

PMID- 23952827
TI  - Issues in the use of stepped wedge cluster and alternative designs in the case of
      pandemics.

PMID- 23952828
TI  - Do commercial interests impact clinical science during a public health emergency?

PMID- 23952829
TI  - Ethics of clinical science in a public health emergency: reflections on the role
      of research ethics boards.

PMID- 23952830
TI  - An ethical analysis of mandatory influenza vaccination of health care personnel:
      implementing fairly and balancing benefits and burdens.
AB  - Health care institutions have paid increasing attention to preventing nosocomial
      transmission of influenza through vaccination of health care personnel. While
      multifaceted voluntary interventions have increased vaccination rates, proponents
      of mandatory programs contend the rates remain unacceptably low. Conventional
      bioethical analyses of mandatory programs are inadequate; they fail to account
      for the obligations of nonprofessional personnel or to justify the weights
      assigned to different ethical principles. Using an ethics framework for public
      health permits a fuller analysis. The framework's focus on fairness accentuates
      the potential differences between the risk of transmitting infection and
      employment status, and the need to equitably evaluate exemptions. The framework's
      emphasis on balancing benefits and burdens highlights the need to justify a
      specific goal and questions the need to exclude all nonmedical exemptions. While
      mandatory vaccination programs are justifiable, greater attention should be paid
      to their implementation. 

PMID- 23952831
TI  - The case for mandatory flu vaccination of children.

PMID- 23952832
TI  - Guidance from vaccination jurisprudence.

PMID- 23952833
TI  - Before the mandate: cultivating an organizational culture of trust and integrity.

PMID- 23952834
TI  - Exemptions from influenza vaccinations for health care personnel based on self or
      identity issues: are they justified?

PMID- 23952835
TI  - Evidence and ethics in mandatory vaccination policies.

PMID- 23952836
TI  - Mandatory influenza vaccination: how far to go and whom to target without
      evidence?

PMID- 23952837
TI  - Professional solidarity: the case of influenza immunization.

PMID- 23952838
TI  - How the weight of the ethical arguments depends on the empirical "facts".

PMID- 23952839
TI  - Applying Kass's public health ethics framework to mandatory health care worker
      immunization: the devil is in the details.

PMID- 23952840
TI  - Response to Open Peer Commentaries on "Ethics of clinical science in a public
      health emergency: drug discovery at the bedside".

PMID- 23952841
TI  - Fabrication of a stretchable solid-state micro-supercapacitor array.
AB  - We fabricated a stretchable micro-supercapacitor array with planar SWCNT
      electrodes and an ionic liquid-based triblock copolymer electrolyte. The
      mechanical stability of the entire supercapacitor array upon stretching was
      obtained by adopting strategic design concepts. First, the narrow and long
      serpentine metallic interconnections were encapsulated with polyimide thin film
      to ensure that they were within the mechanical neutral plane. Second, an array of
      two-dimensional planar micro-supercapacitor with SWCNT electrodes and an ion-gel
      type electrolyte was made to achieve all-solid-state energy storage devices. The
      formed micro-supercapacitor array showed excellent performances which were stable
      over stretching up to 30% without any noticeable degradation. This work shows the
      strong potential of a stretchable micro-supercapacitor array in applications such
      as wearable computers, power dressing, electronic newspapers, paper-like mobile
      phones, and other easily collapsible gadgets. 

PMID- 23952842
TI  - It's up to you: a multi-message, phased driver facility campaign to increase
      organ donation registration rates in Illinois.
AB  - BACKGROUND: The present project applied successful strategies employed in
      previous driver facility campaigns occurring during the inception of a registry
      to examine whether these approaches are effective in growing a mature registry, a
      registry where the majority of individuals have had the opportunity to register
      as an organ donor. METHODS: Driver facilities (N = 40) in Illinois with high (n =
      20) and low (n = 20) organ donation registration percentages were selected and
      served as either intervention or control sites for the campaign. RESULTS: Among
      facilities with historically high and low registration percentages, support for
      the campaign was found with the intervention facilities experiencing higher organ
      donation registration rates compared with control facilities. In addition, the
      results provide partial support for the effectiveness of employing a multi
      message, phased driver facility intervention in states with a mature registry.
      CONCLUSION: The practical implications of utilizing driver facility campaigns in
      states with an established first-person consent registry also are discussed.

PMID- 23952843
TI  - Corneal ectasia after LASIK in a patient with normal scheimpflug evaluation but a
      high Ectasia Risk Score.
AB  - PURPOSE: To present a case of ectasia after LASIK that developed in a patient
      with normal Scheimpflug imaging but a high Ectasia Risk Score System (ERSS)
      score. METHODS: Case report. RESULTS: A 24-year-old woman with no preoperative
      abnormalities on Scheimpflug evaluation but a cumulative ERSS risk of 4 (high
      risk) in the right eye and 3 (medium risk) in the left eye developed ectasia in
      both eyes 27 months after LASIK. She underwent ultraviolet-A corneal collagen
      cross-linking, with no signs of further progression. CONCLUSIONS: In this case,
      the ERSS was effective at predicting ectasia risk despite normal Scheimpflug
      imaging and only mild asymmetry on Placido topography.

PMID- 23952844
TI  - Association between ocular dominance and refractive asymmetry.
AB  - PURPOSE: To investigate the association between ocular dominance (sighting
      dominance) and refractive asymmetry in phakic patients. METHODS: This
      retrospective study included 3,012 patients with a mean age of 29.0 +/- 5.3 years
      (range: 20 to 39 years). Refractive error was determined with cycloplegic
      refraction and axial length was determined with IOLMaster (Carl Zeiss Meditec,
      Dublin, CA). Ocular dominance was assessed using the hole-in-the-card test.
      RESULTS: The right and left eyes were dominant in 77.7% and 22.3% of the
      patients, respectively. In the high anisometropia group (? 2.0 diopters), the non
      dominant eyes had significantly higher myopic spherical equivalents and longer
      axial lengths than the dominant eyes (P < .05). However, there were no
      significant differences in these parameters in the low anisometropia group.
      CONCLUSION: The current study revealed that non-dominant eyes had a greater
      myopic refractive error and longer axial length than the dominant eyes,
      especially in the patients who had high amounts of anisometropia.

PMID- 23952845
TI  - The American Thoracic Society methods in epidemiologic, clinical, and operations
      research program. A research capacity-building program in low- and middle-income
      countries.
AB  - Respiratory diseases are a major cause of morbidity and mortality worldwide. The
      greatest impact of many of these diseases is felt in low- and middle-income
      countries, but their control and management is hampered by lack of accurate
      estimates of their prevalence, risk factors, and distribution, and knowledge of
      the social and cultural setting in which they occur. Providing enough information
      for cost-effective response to respiratory diseases requires research by trained
      investigators and public health personnel. The American Thoracic Society (ATS)
      Methods in Epidemiologic, Clinical, and Operations Research (MECOR) Program was
      launched in 1994 to provide a sustainable means of increasing local and national
      research capacity aimed at addressing this need. As of March 2013, approximately
      1,015 students have completed at least one level of the training program. Post
      MECOR, 64% of participants have published a medical paper, 79% have presented at
      a scientific or academic meeting, 51% have submitted a research protocol for
      funding, and 42% have had one funded. One-quarter have been awarded an academic
      or clinical fellowship, and 78% reported that MECOR had made a significant or
      extremely important contribution to their professional life and accomplishments.
      Future challenges include funding, recruitment of local faculty, helping to build
      the research infrastructure in MECOR countries, and providing ongoing mentoring
      for research. 

PMID- 23952846
TI  - Chronic pain and pain medication use in chronic obstructive pulmonary disease. A
      cross-sectional study.
AB  - RATIONALE: Pain is a common problem for patients with chronic obstructive
      pulmonary disease (COPD). However, pain is minimally discussed in COPD management
      guidelines. OBJECTIVES: The objective of this study was to describe chronic pain
      prevalence among patients with COPD compared with similar patients with other
      chronic diseases in a managed care population in the southwestern United States
      (age >= 40 yr). METHODS: Using data for the period January 1, 2006 through
      December 31, 2010, patients with COPD were matched to two control subjects
      without COPD but with another chronic illness based on age, sex, insurance, and
      healthcare encounter type. Odds ratios (OR) for evidence of chronic pain were
      estimated using conditional logistic regression. Pulmonary function data for 200
      randomly selected patients with COPD were abstracted. MEASUREMENTS AND MAIN
      RESULTS: Retrospectively analyzed recurrent pain-related utilization (diagnoses
      and treatment) was considered evidence of chronic pain. The study sample
      comprised 7,952 patients with COPD (mean age, 69 yr; 42% male) and 15,904
      patients with other chronic diseases (non-COPD). Patients with COPD compared with
      non-COPD patients had a higher percentage of chronic pain (59.8 vs. 51.7%; P <
      0.001), chronic use of pain-related medications (41.2 vs. 31.5%; P < 0.001), and
      chronic use of short-acting (24.2 vs. 15.1%; P < 0.001) and long-acting opioids
      (4.4 vs. 1.9%; P < 0.001) compared with non-COPD patients. In conditional
      logistic regression models, adjusting for age, sex, Hispanic ethnicity, and
      comorbidities, patients with COPD had higher odds of chronic pain (OR, 1.56; 95%
      confidence interval [CI], 1.43-1.71), chronic use of pain-related medications
      (OR, 1.60; 95% CI, 1.46-1.74), and chronic use of short-acting or long-acting
      opioids (OR, 1.74; 95% CI, 1.57-1.92). CONCLUSIONS: Chronic pain and opioid use
      are prevalent among adults with COPD. This finding was not explained by the
      burden of comorbidity.

PMID- 23952847
TI  - Nodular bronchiectatic Mycobacterium avium complex pulmonary disease. Natural
      course on serial computed tomographic scans.
AB  - RATIONALE: Existing literature is inconclusive regarding how the nodular
      bronchiectatic form of Mycobacterium avium complex (MAC) disease will progress
      without treatment and when treatment initiation should be considered. OBJECTIVES:
      To assess the natural course of MAC pulmonary disease by serial thin-section
      computed tomography (CT). METHODS: Of 339 patients with nodular bronchiectatic
      form of MAC disease, we selected 265 untreated patients who had serial CTs (mean
      observation period, 32 +/- 21 mo). Two independent chest radiologists reviewed
      retrospectively all CT scans for the presence and extent of lung abnormalities
      (maximal total score, 30). MEASUREMENTS AND MAIN RESULTS: Of 265 patients, 126
      patients (48%) had disease that had progressed and that needed treatment owing to
      radiologic deterioration or worsening symptoms, and the remaining 139 patients
      (52%) did not. On multivariate analysis, the presence of cavity (adjusted hazard
      ratio, 2.06; P = 0.004) and consolidation (adjusted hazard ratio, 1.55; P =
      0.019) at initial CT remained as independent factors associated with disease
      progression and treatment requirement. The presence of cavitary lesions
      demonstrated the highest positive predictive value (61%) and significant
      correlation (P = 0.005) with smear positivity. Differences in the extent of each
      pattern and total CT score in the serial studies were significantly larger (P <
      0.05) in patients requiring treatment. The total CT score increased by 2.41 in
      the treatment-requiring group compared with 0.25 in the group that did not
      receive treatment. CONCLUSIONS: Without treatment, about half of patients
      demonstrate progressive disease on serial CT over a mean follow-up period of 32
      months and, thus, required treatment. Patients showing cavities or consolidation
      on initial CT are more likely to have progressive disease and thus to require
      treatment eventually.

PMID- 23952848
TI  - Pilot study of extracorporeal carbon dioxide removal to facilitate extubation and
      ambulation in exacerbations of chronic obstructive pulmonary disease.
AB  - RATIONALE: Acute exacerbations of chronic obstructive pulmonary disease (COPD)
      requiring invasive mechanical ventilation (IMV) are associated with significant
      morbidity and mortality. Extracorporeal carbon dioxide removal (ECCO2R) may
      facilitate extubation and ambulation in these patients and potentially improve
      outcomes. OBJECTIVES: We assessed the feasibility of achieving early extubation
      and ambulation in subjects requiring IMV for exacerbations of COPD using single
      site ECCO2R. METHODS: Five subjects with exacerbations of COPD with uncompensated
      hypercapnia requiring IMV were enrolled in this single-center, prospective,
      feasibility trial using a protocol of ECCO2R, extubation, and physical
      rehabilitation. The primary endpoint was extubation within 72 hours of starting
      ECCO2R. MEASUREMENTS AND MAIN RESULTS: Mean preintubation pH and PaCO2 were 7.23
      +/- 0.05 and 81.6 +/- 15.9 mm Hg, respectively. All subjects met the primary
      endpoint (median duration, 4 h; range, 1.5-21.5 h). Mean duration of
      extracorporeal support was 193.0 +/- 76.5 hours. Mean time to ambulation after
      extracorporeal initiation was 29.4 +/- 12.6 hours. Mean maximal ambulation on
      extracorporeal support was 302 feet (range, 70-600). Four subjects were
      discharged home, and one underwent planned lung transplantation. Two minor
      bleeding complications occurred. There were no complications from mobilization on
      extracorporeal support. CONCLUSIONS: ECCO2R facilitates early extubation and
      ambulation in exacerbations of COPD requiring IMV and has the potential to serve
      as a new paradigm for the management of a select group of patients. Rigorous
      clinical trials are needed to corroborate these results and to investigate the
      effect on long-term outcomes and cost effectiveness over conventional management.

PMID- 23952849
TI  - Risk factors for long-term brain dysfunction after chronic critical illness.
AB  - RATIONALE: Factors associated with long-term brain dysfunction (LTBD) in
      survivors of chronic critical illness (CCI) have not been explored but may be
      important for clinical practice and planning by patients, families, and
      providers. OBJECTIVES: To identify risk factors for LTBD after treatment for CCI
      and to explore the association between acute delirium and coma during hospital
      treatment and LTBD. METHODS: A prospective cohort study of adults admitted to a
      respiratory care unit for treatment of CCI. MEASUREMENTS AND MAIN RESULTS: Using
      the Confusion Assessment Method for ICU and the Richmond Agitation and Sedation
      Scale, we evaluated patients for delirium and coma during their hospital
      treatment for CCI. We collected data on other potential risk factors for LTBD by
      prospectively reviewing the patients' medical records and interviewing
      surrogates. We contacted survivors by telephone at 6 months after discharge to
      assess brain function using the telephone Confusion Assessment Method. Among 385
      patients treated for CCI, 213 (56.1%) were dead at 6 months, and 108 of 167
      (64.7%) of survivors were impaired. We used multinomial logistic regression in
      which the outcomes were (1) death, (2) brain dysfunction, and (3) survival
      without LTBD. Older patients, patients with higher Acute Physiology Score, and
      those with multiple complications during treatment for CCI were more likely to
      have LTBD. Acute brain dysfunction during hospital treatment was also associated
      with an increased risk of LTBD (odds ratio, 2.14; 95% confidence interval, 1.02
      4.52). CONCLUSIONS: LTBD after treatment for CCI is associated with brain
      dysfunction during such treatment as well as with older age and higher severity
      of illness of the patients.

PMID- 23952850
TI  - Quality of life and healthcare use in a randomized controlled lung cancer
      screening study.
AB  - RATIONALE: Understanding the quality of life of lung cancer screening program
      participants, and the impact of program participation on quality of life and
      healthcare use, will help in the assessment of the value of screening.
      OBJECTIVES: Determine the quality of life of participants in a lung cancer
      screening study and assess the effect of an abnormal screening finding on quality
      of life and healthcare use. METHODS: Quality-of-life measures and data on the use
      of healthcare services were collected prospectively during a randomized
      controlled lung cancer screening trial using chest radiography with computer
      aided detection. Comparisons of baseline measures were made with U.S. population
      norms for the EuroQol 5-Dimension index. The impact of receiving a message of the
      presence of a lung nodule was assessed for all measures. MEASUREMENTS AND MAIN
      RESULTS: A total of 1,424 subjects participated. Twenty-five actionable nodules
      were reported. Baseline EuroQol 5-Dimension index scores were higher than U.S.
      population norms (P < 0.0001). The EuroQol 5-Dimension index score and St.
      George's Respiratory Questionnaire symptom score showed a significant change
      toward poorer quality of life after notification of the presence of a lung nodule
      (0.940 vs. 0.877, P = 0.022, and 25.7 vs. 34.0, P = 0.005, respectively). Chest
      imaging within 6 months of the screening examination occurred more frequently in
      those notified of a lung nodule (25.5 vs. 9.3%, P = 0.002). CONCLUSIONS: Those
      who choose to enter a lung cancer screening program have a high baseline quality
      of life. The report of an abnormal screening finding can lower the quality of
      life and lead to increased chest imaging. Clinical trial registered with
      www.clinicaltrials.gov (NCT01663155).

PMID- 23952851
TI  - What the heck is a "nodule"? A qualitative study of veterans with pulmonary
      nodules.
AB  - RATIONALE: Every year, hundreds of thousands of patients are diagnosed with
      incidentally detected pulmonary nodules, and if lung cancer screening is widely
      implemented, thousands more will be identified. The psychosocial outcomes
      associated with incidental nodule detection in general practice settings are
      virtually unknown. OBJECTIVES: The purpose of this study was to explore the
      experiences of patients with incidentally diagnosed pulmonary nodules. METHODS:
      We conducted qualitative interviews of 19 veterans with incidentally detected
      pulmonary nodules. We used qualitative description for the analysis, focusing on
      patients' information exchange and other communication behaviors with their
      clinicians. MEASUREMENTS AND MAIN RESULTS: The patients were cared for by primary
      care clinicians and had small nodules that were unlikely to be malignant.
      Patients did not understand the term "nodule" although they knew it was related
      to cancer. They also did not understand the follow-up plan and most were unable
      to obtain better information from their clinician or other sources. Most patients
      experienced nodule-related distress that was usually mild, although sometimes
      severe. This distress was sometimes mitigated by patients' confidence in their
      clinician. Most patients wanted more and better information about their nodule.
      CONCLUSIONS: Veterans from one hospital have little understanding of what nodules
      are, the likelihood of malignancy, and the follow-up plan. Their reaction to this
      knowledge deficit is variable and is likely related to preferred communication
      behaviors with their clinician. Evaluating communication in other settings is
      important to confirm these findings and to refine mechanisms to improve patient
      centered care for those with incidentally detected pulmonary nodules.

PMID- 23952852
TI  - The safety of thoracentesis in patients with uncorrected bleeding risk.
AB  - BACKGROUND: Thoracentesis is commonly performed to evaluate pleural effusions.
      Many medications (warfarin, heparin, clopidogrel) or physiological factors
      (elevated International Normalized Ratio [INR], thrombocytopenia, uremia)
      increase the risk for bleeding. Frequently these medications are withheld or
      transfusions are performed to normalize physiological parameters before a
      procedure. The safety of performing thoracentesis without correction of these
      bleeding risks has not been prospectively evaluated. METHODS: This prospective
      observational cohort study enrolled 312 patients who underwent thoracentesis. All
      patients were evaluated for the presence of risk factors for bleeding. Hematocrit
      levels were obtained pre- and postprocedure, and the occurrence of postprocedural
      hemothorax was evaluated. MEASUREMENTS AND MAIN RESULTS: Thoracenteses were
      performed in 312 patients, 42% of whom had a risk for bleeding. Elevated INR,
      secondary to liver disease or warfarin, and renal disease were the two most
      common etiologies for bleeding risk, although many patients had multiple
      potential bleeding risks. There was no significant difference in pre- and
      postprocedural hematocrit levels in patients with a bleeding risk when compared
      with patients with no bleeding risk. No patient developed a hemothorax as a
      result of the thoracentesis. CONCLUSIONS: This single-center, observational study
      suggests that thoracentesis may be safely performed without prior correction of
      coagulopathy, thrombocytopenia, or medication-induced bleeding risk. This may
      reduce the morbidity associated with transfusions or withholding of medications.

PMID- 23952853
TI  - Bronchoscopic findings and bleeding control predict survival in patients with
      solid malignancies presenting with mild hemoptysis.
AB  - BACKGROUND: Regardless of its volume, hemoptysis is a concerning symptom. Mild
      hemoptysis and its significance in patients with solid malignancies has not been
      studied. METHODS: We conducted a retrospective chart review of patients with
      solid malignancies who presented for evaluation of mild hemoptysis. In this
      population, we studied the impact of bronchoscopic findings and endobronchial
      therapies on overall survival and bleeding recurrence. Patients were categorized
      into four groups on the basis of the presence or absence of active bleeding and
      endobronchial disease at the time of initial bronchoscopy: active bleeding with
      endobronchial lesion (AB/EBL), active bleeding without endobronchial lesion
      (AB/no-EBL), absence of active bleeding but with endobronchial lesion (no
      AB/EBL), and absence of active bleeding and endobronchial lesion (no-AB/no-EBL).
      MEASUREMENTS AND MAIN RESULTS: Ninety-five of the 112 patients with solid
      malignancies and mild hemoptysis underwent bronchoscopies. There was a
      significantly lower median survival time for patients with bronchoscopic findings
      of active bleeding and endobronchial lesion compared with patients with no active
      bleeding and/or no endobronchial lesion (3.48 mo; 95% confidence interval [CI],
      2.14-6.05). On a multivariate analysis, factors independently associated with
      improved survival were higher hemoglobin values (hazard ratio [HR], 0.78; 95% CI,
      0.67-0.91) and cessation of hemoptysis without recurrence at 48 hours (HR, 0.43;
      95% CI, 0.22-0.84). Variables independently associated with worse survival were
      disease stage (HR, 10.8; 95% CI, 2.53-46.08) and AB/EBL (HR, 3.20; 95% CI, 1.74
      5.89). CONCLUSIONS: In patients with solid malignancies presenting with mild
      hemoptysis, bronchoscopic findings of AB/EBL are associated with decreased
      survival. Hemoptysis control without recurrence at 48 hours after endobronchial
      intervention may improve survival.

PMID- 23952854
TI  - Occurrence and predictors of obstructive sleep apnea in a revascularized coronary
      artery disease cohort.
AB  - BACKGROUND: Knowledge about the prevalence of obstructive sleep apnea (OSA) in
      coronary artery disease (CAD) is insufficient. The aim of the current report was
      to evaluate the occurrence and predictors of OSA among revascularized patients
      with CAD within the framework of a randomized controlled trial (Randomized
      Intervention with CPAP in Coronary Artery Disease and Sleep Apnea [RICCADSA]),
      evaluating the impact of continuous positive airway pressure on cardiovascular
      outcomes in CAD patients with OSA. MATERIAL AND METHODS: All patients undergoing
      percutaneous coronary intervention or coronary artery bypass grafting between
      September 2005 and November 2010 (n = 1,291) were invited to participate.
      Anthropometrics and medical history were obtained, ambulatory sleep recording was
      performed, and all subjects completed the Epworth Sleepiness Scale (ESS)
      questionnaire. RESULTS: In total, 662 patients participated in the sleep study.
      OSA, defined as an apnea-hypopnea index equal to or greater than 15/hour, was
      found among 422 (63.7%). The prevalence of hypertension was 55.9%; obesity (body
      mass index >= 30 kg/m2), 25.2%; diabetes mellitus, 22.1%; and current smoking,
      18.9%. The patients with CAD who did not participate in the study demonstrated an
      almost similar anthropometric and clinical profile compared with the studied
      group. The majority (61.8%) of the patients with OSA were nonsleepy (ESS score <
      10). Patients with OSA had a higher prevalence of obesity, hypertension, diabetes
      mellitus, and history of atrial fibrillation, whereas current smoking was more
      common in the non-OSA group. Age, male sex, body mass index, and ESS score, but
      not comorbidities, were independent predictors of OSA. CONCLUSIONS: The
      occurrence of unrecognized OSA in this revascularized CAD cohort was higher than
      previously reported. We suggest that OSA should be considered in the secondary
      prevention protocols in CAD.

PMID- 23952855
TI  - We help the world breathe.

PMID- 23952856
TI  - Science is dispassionate, we are told.

PMID- 23952857
TI  - The old order changeth, yielding place to the new.

PMID- 23952858
TI  - Editors' introduction to ATS Reports.

PMID- 23952859
TI  - Pulmonary fibrosis in sarcoidosis. Clinical features and outcomes.
AB  - Sarcoidosis is a systemic inflammatory disease with a predilection for the
      respiratory system. Although most patients enter remission and have good long
      term outcomes, up to 20% develop fibrotic lung disease, whereby granulomatous
      inflammation evolves to pulmonary fibrosis. There are several radiographic
      patterns of pulmonary fibrosis in sarcoidosis; bronchial distortion is common,
      and other patterns, including honeycombing, are variably observed. The
      development of pulmonary fibrosis is associated with significant morbidity and
      can be fatal. Dyspnea, cough, and hypoxemia are frequent clinical manifestations.
      Pulmonary function testing often demonstrates restriction from parenchymal
      involvement, although airflow obstruction from airway-centric fibrosis is also
      recognized. Complications of fibrotic pulmonary sarcoidosis include pulmonary
      hypertension from capillary obliteration and chronic aspergillus disease, with
      hemoptysis a common and potentially life-threatening manifestation.
      Immunosuppression is not always indicated in end-stage sarcoidosis. Lung
      transplantation should be considered for patients with severe fibrotic pulmonary
      sarcoidosis, as mortality is high in these patients. 

PMID- 23952860
TI  - Emerging indications for extracorporeal membrane oxygenation in adults with
      respiratory failure.
AB  - Recent advances in technology have spurred the increasing use of extracorporeal
      membrane oxygenation (ECMO) in patients with severe hypoxemic respiratory
      failure. However, this accounts for only a small percentage of patients with
      respiratory failure. We envision the application of ECMO in many other forms of
      respiratory failure in the coming years. Patients with less severe forms of acute
      respiratory distress syndrome, for instance, may benefit from enhanced lung
      protective ventilation with the very low tidal volumes made possible by direct
      carbon dioxide removal from the blood. For those in whom hypercapnia
      predominates, extracorporeal support will allow for the elimination of invasive
      mechanical ventilation in some cases. The potential benefits of ECMO may be
      further enhanced by improved techniques, which facilitate active mobilization.
      Although ECMO for these and other expanded applications is under active
      investigation, it has yet to be proven beneficial in these settings in rigorous
      controlled trials. Ultimately, with upcoming and future technological advances,
      there is the promise of true destination therapy, which could lead to a major
      paradigm shift in the management of respiratory failure. 

PMID- 23952861
TI  - Reducing human exposure to Mycobacterium avium.
AB  - In light of the increasing prevalence of Mycobacterium avium pulmonary disease
      and the challenges of treating patients with M. avium infection, consideration of
      measures to reduce exposure is warranted. Because M. avium inhabits water and
      soil, humans are surrounded by that opportunistic pathogen. Because infection has
      been linked to the presence of M. avium in household plumbing, increasing hot
      water temperature, reducing aerosol (mist) exposures in bathrooms and showers,
      and installing filters that prevent the passage of mycobacteria will likely
      reduce M. avium exposure. Granular activated carbon (charcoal) filters support
      the growth of M. avium and should be avoided. When gardening, avoid the
      inhalation of soil dusts by using a mask or wetting the soil because peat-rich
      potting soils have high numbers of mycobacteria. 

PMID- 23952862
TI  - The American Thoracic Society Methods in Epidemiologic, Clinical, and Operations
      Research program. Research capacity building in action.

PMID- 23952863
TI  - Communicating with Congress.
AB  - Influencing policy to improve health can be considered an extension of health
      care workers' duty to help people. Communicating with elected representatives is
      a basic mechanism to effect lasting change. Communications that influence public
      officials should be clear, concise, courteous, and logical. They are strengthened
      by citing evidence and example. They must recommend a course of action, which
      should be principled and related to the representative's constituents. 

PMID- 23952864
TI  - Eosinophils. An unexpected delivery.

PMID- 23952865
TI  - Endobronchial ultrasound. When to venture into the vasculature.

PMID- 23952866
TI  - Ventilatory failure. Can you sustain what you need?

PMID- 23952867
TI  - An 84-year-old woman with long-standing excessive daytime sleepiness.

PMID- 23952868
TI  - Perspective of a daughter turned advocate.

PMID- 23952870
TI  - Efficacy of sirolimus therapy for chylous effusions in lymphangioleiomyomatosis.

PMID- 23952871
TI  - An official American Thoracic Society proceedings: work-related asthma and airway
      diseases. Presentations and discussion from the Fourth Jack Pepys Workshop on
      Asthma in the Workplace.
AB  - Work-related asthma is a common occupational lung disease. The scope of the
      Fourth Jack Pepys Workshop that was held in May 2010 went beyond asthma to
      include discussion of other occupational airway diseases, in particular
      occupationally related chronic obstructive pulmonary disease (COPD) and
      bronchiolitis. Aspects explored included public health considerations,
      environmental aspects, outcome after diagnosis, prevention and surveillance, and
      other work-related obstructive airway diseases. Consistent methods are needed to
      accurately estimate the comparative burden of occupation-related airway diseases
      among different countries. Challenges to accomplishing this include variability
      in health care delivery, compensation systems, cultural contexts, and social
      structures. These factors can affect disease estimates, while heterogeneity in
      occupations and workplace exposures can affect the underlying true prevalence of
      morbidity. Consideration of the working environment included discussion of
      practical methods of limiting exposure to respiratory sensitizers, methods to
      predict new sensitizers before introduction into workplaces, the role of
      legislated exposure limits, and models to estimate relative validity of various
      ameliorative measures when complete avoidance of the sensitizer is not feasible.
      Other strategies discussed included medical surveillance measures and education,
      especially for young individuals with asthma and new workers about to enter the
      workforce. Medical outcomes after development of sensitizer-induced occupational
      asthma are best following earlier diagnosis and removal from further exposure,
      but a subset may be able to continue working safely provided that exposure is
      reduced under close follow-up monitoring. It was recognized that occupationally
      related COPD is common but underappreciated, deserving further study and
      prevention efforts. 

PMID- 23952872
TI  - Clinical benefits and economic impact of post-surgical care provided by
      pharmacists in a Canadian hospital.
AB  - OBJECTIVE: Clinical pharmacists improve the quality of patient care by reducing
      adverse drug events (ADEs), length of stay and mortality. This impact is
      currently not well described in surgery. The objective was to evaluate clinical
      and economic outcomes after clinical pharmacist services were added to two
      general surgical wards in an adult hospital. METHODS: This was a prospective,
      observational study. All clinical interventions to resolve drug therapy problems
      were documented and assessed for severity, value and the probability of
      preventing an ADE. Cost avoidance was calculated using two methods: by avoiding
      additional days in hospital (CA$3593/ADE) or additional hospital costs
      ($7215/ADE). Two clinical pharmacy specialists and the surgical care pharmacist
      independently categorized the interventions; disagreements were resolved by
      consensus. KEY FINDINGS: The pharmacists made 1097 interventions in 6 months with
      a 98% acceptance rate by surgical staff. Half of the interventions were rated
      significant for severity (561, 51.1%) and value (559, 51.0%). One-quarter of the
      interventions had a 40% or greater probability of preventing an ADE (270, 24.6%).
      Cost avoidance was estimated to be $0.68-1.36 million or $617-1239 per
      intervention. Pharmacists avoided an additional 867 days in the hospital for
      surgical patients. CONCLUSION: The pharmacist's role in the management of the
      drug therapy needs of the post-surgical patient has the potential to improve
      clinical and patient outcomes and avoid healthcare costs. The inclusion of
      clinical pharmacists in surgical wards may result in $7 in savings for every $1
      invested.

PMID- 23952873
TI  - Rate and Level of Learning as Functions af Information-Processing Characteristics
      of the Learner and the Task.
AB  - This study examined relationships among information-processing characteristics of
      the learner, dominant information-processing component of tasks, and the rate and
      level of mastery of selected motor tasks. Sixth grade children (n=60) were
      classified as high, moderate, or low visual and/or proprioceptive information
      processors and asked to learn a fine perceptual-motor task and one of two gross
      perceptual-motor tasks that differed in the relative importance of visual and
      proprioceptive components. When visual and proprioceptive demands of a task were
      equivalent, high information processors showed higher levels of task mastery than
      low information processors; when proprioceptive tasks demands were dominant,
      results were equivocal. If processing demands were high, high proprioceptive
      information processors exhibited higher performance than did low subjects. When
      demands were less, performance level was not significantly affected. Rate of task
      mastery was never affected by these factors. 

PMID- 23952874
TI  - A test of the schema theory of discrete motor learning.
AB  - The recall schema in a response class of discrete movements was investigated,
      with variability of practice being manipulated before transfer to a new instance
      in the response class. After the transfer, the varied-practice group performance
      was superior to the continuous practice group. The interaction of the low-and
      high-variability groups from training to recall performance supported the
      prediction that a group with more variable training would exhibit an increased
      rate of learning when introduced to a new instance of the response class. After
      two days, the superiority of the high-variability group over the low disappeared,
      suggesting the memory representations of the two groups were no different under
      withdrawal of knowledge of results. 

PMID- 23952875
TI  - Fatigue effects in running.
AB  - Effects of fatigue were assessed on 12 female subjects who were filmed at two
      stages of a maximal-effort, gross physical performance task (running).
      Comparisons were then made between selected temporal and kinematic parameters
      describing the activity: The results appear to support the concept that fatigue
      does not simply produce a uniform reduction in the components of a movement
      pattern but, rather, changes their relationship completely. 

PMID- 23952876
TI  - Dual-task performance and the hick-hyman law of choice reaction time.
AB  - The slope, intercept, and linearity of the function relating RT and stimulus
      information reflect different aspects of information processing. This experiment
      determined which aspects of information processing are affected by the presence
      of a secondary task. Subjects (n = 12) performed a one-dimensional tracking task
      concurrently with a choice RTtask. Subjects also performed each task singly. Half
      of the subjects performed under dual-task conditions with adjacent displays, half
      with separated displays. For the adjacent group the tracking task had no reliable
      effect on either the slope, intercept, or linearity of the relation. Scanning
      affected only the intercept for the separated group. Error on the tracking task
      was found to increase linearly with increased processing load on the choice RT
      task for both groups. The results are interpreted as supporting a modified single
      channel theory. 

PMID- 23952877
TI  - The ischemic nerve block and skilled movement.
AB  - Accuracy of skilled movement was investigated in a serial positioning task with
      the index finger reversibly deafferented by an ischemic nerve block. The reflex
      response to sudden muscle stretch was monitored at systematic intervals following
      cuff application. Serial positioning in the verified absence of stretch reflexes
      was significantly less accurate and more variable than under normal conditions.
      These findings were discussed in terms of the "servo-assistance" hypothesis for
      the control of movement and the limits of accuracy that can be achieved in the
      absence of kinesthesis. 

PMID- 23952879
TI  - Nature of kinesthesis as measured through techniques derived from the theory of
      signal detectability.
AB  - Forearm movement discrimination sensitivity, as measured through techniques
      derived from the theory of signal detectability, was studied in relationship to
      forearm movement reproduction sensitivity. As a secondary problem, the two
      identified measures of kinesthetic sensitivity were also studied in relation to
      the independent variables of extent of forearm angular movement, direction of
      movement (supination or pronation), and order that the discrimination and
      reproduction tests were administered (transfer effect of first test on the
      second). There was little statistical relationship between kinesthetic
      discrimination and reproduction sensitivity measures. Both measures of
      kinesthetic sensitivity were similar in their relationship to the independent
      variables of extent, direction, and transfer. In both cases, the only significant
      main effect was that of extent (short movements more accurate than long).
      Kinesthetic discrimination was observed to be a much more stable measurement of
      kinesthetic sensitivity than movement reproduction. This study was funded by a
      Faculty Research Grant awarded by Kansas State University. Requests for reprints
      should be sent to Richard H. Cox, Department of Physical Education, Kansas State
      University, Manhattan, Kansas 66506. 

PMID- 23952878
TI  - Application of signal detection theory to perceptual-motor skills.
AB  - A signal-detection paradigm was utilized to examine subjects' sensitivity to
      situational and sensory-motor stimuli in predicting motor skill performance.
      College-level and professional basketball players attempted uncontested shots
      from assigned positions on the basketball court. Before each shot was released,
      both the shooter and a passive observer were required to predict whether it would
      be successful. Signal-detection analysis revealed no evidence for greater
      sensitivity of the shooter over the passive observer or an idealized statistical
      predictor using only floor position as a prediction cue. Both shooters and
      passive observers were too optimistic when strong penalties were imposed for
      incorrect predictions of success. 

PMID- 23952880
TI  - The effect of non-traumatic audible stress on learning of two motor skills.
AB  - Ability to learn two motor tasks while exposed to a continuous 1000-Hz tone of
      105 db was compared with learning the tasks without noise. While wearing
      earphones, half of 40 subjects learned the stabilometer task while the noise was
      presented and learned the ring-peg task with no noise. The other half had the
      reverse procedure. For college age men, learning motor skills was not adversely
      affected by the noise. 

PMID- 23952881
TI  - Motor short-term memory measures as a function of methodology.
AB  - Nine combinations (n=8) of methods for having subjects move their limb during
      presentation of criterion movements and return to the starting location were
      studied on a linear positioning apparatus. The results indicated, for absolute,
      variable, and constant errors, an interaction between the methods used in
      returning the limb from the endpoint of the criterion movement and the
      reproduction performance at two delay conditions of 0 and 20 sec. In addition,
      for absolute and constant errors, both the methods of moving the limb for the
      criterion movement and the methods of returning to the starting position
      interacted with reproduction of three movement amplitudes (15, 30, and 45 cm).
      For variable error only the methods of returning to the starting position
      differentially influenced performance at the three amplitudes. These results
      indicated that methodological variables can interact with independent variables
      in the short-term memory paradigm and design of future investigations should take
      this into account. 

PMID- 23952882
TI  - A note concerning analysis of error scores from motor-memory research.
AB  - Exception is taken to the statistical analysis for motor memory research
      suggested by Roy (1976) in his paper on "Measuring change in motor memory. " The
      hazardous effects of multicollinearity which result from using AE(or E), CE, and
      VE as multiple dependent variables in MANOVA are explained and an alternate
      strategy for statistical analysis is suggested. I would like to express my
      appreciation to Ken Brewer, Program of Evaluation and Research Design at Florida
      State University, for his assistance with the major points of this paragraph. 

PMID- 23952883
TI  - Measuring change.
AB  - Corroboration is given to statements made by Thomas (1977) regarding the problem
      of multicollinearity in the use of AE, CE, and VE in the ANOVA technique.
      Additional comments are made with reference to the analysis of change in motor
      memory. 

PMID- 23952885
TI  - Platinum-coated copper nanowires with high activity for hydrogen oxidation
      reaction in base.
AB  - Platinum (Pt)-coated copper (Cu) nanowires (Pt/CuNWs) are synthesized by the
      partial galvanic displacement of CuNWs and have a 100 nm diameter and are 25-40
      MUm length. Pt/CuNWs are studied as a hydrogen oxidation reaction (HOR) catalyst
      in base along with Cu templated Pt nanotubes (PtNT (Cu)), a 5% Cu monolayer on a
      bulk polycrystalline Pt electrode (5% ML Cu/BPPt), BPPt, and carbon supported Pt
      (Pt/C). Comparison of these catalysts demonstrates that the inclusion of Cu
      benefited the HOR activity of Pt/CuNWs likely by providing compressive strain on
      Pt; surface Cu further aids in hydroxyl adsorption, thereby improving the HOR
      activity of Pt/CuNWs. Pt/CuNWs exceed the area and mass exchange current
      densities of carbon supported Pt by 3.5 times and 1.9 times. 

PMID- 23952884
TI  - Hemorrhage risk, surgical management, and functional outcome of brainstem
      cavernous malformations.
AB  - OBJECT: The aim of this study was to evaluate the pre- and postoperative
      rehemorrhage risk, neurological function outcome, and prognostic factors of
      surgically treated brainstem cavernous malformations (CMs) with long-term follow
      up. METHODS: The authors conducted a retrospective review of the clinical data
      from 242 patients with brainstem CMs that were surgically treated between 1999
      and 2010. Patient charts, imaging findings, and outcomes were examined. RESULTS:
      The study included 242 patients, with a male-to-female ratio of 1.3 and mean age
      of 32.6 years. The mean modified Rankin Scale scores on admission, at discharge,
      at 3 and 6 months after surgery, and at recent evaluation were 2.2, 2.6, 2.3,
      1.8, and 1.5, respectively. The preoperative calculated annual hemorrhage and
      rehemorrhage rates were 5.0% and 60.9%, respectively. The complete resection rate
      was 95%. Surgical morbidity occurred in 112 patients (46.3%). Eighty-five
      patients (35.1%) demonstrated worsened condition immediately after surgery; 34
      (41.0%) and 51 (61.4%) of these patients recovered to their baseline level within
      3 and 6 months after surgery, respectively. At a mean follow-up of 89.4 months,
      the patients' condition had improved in 147 cases (60.7%), was unchanged in 70
      cases (28.9%), and had worsened in 25 cases (10.3%). A total of 8 hemorrhages
      occurred in 6 patients, and the postoperative annual hemorrhage rate was 0.4%.
      Permanent morbidity remained in 65 patients (26.9%). The adverse factors for
      preoperative rehemorrhage were age >= 50 years, size >= 2 cm, and perilesional
      edema. The risk factors for postoperative hemorrhage were developmental venous
      anomaly and incomplete resection. The independent adverse factors for long-term
      outcome were increased age, multiple hemorrhages, ventral-seated lesions, and
      poor preoperative status. Favorable, complete improvement in the postoperative
      deficits over time was correlated with good preoperative neurological function
      and continuing improvement thereafter. CONCLUSIONS: Favorable long-term outcomes
      and significantly low postoperative annual hemorrhage rates were achieved via
      surgery. Total resection should be attempted with an aim of minimal injury to
      neurological function; however, postoperative deficits can improve during the
      postoperative course. Close follow-up with radiological examination is proposed
      for patients with adverse factors predictive of rehemorrhage.

PMID- 23952886
TI  - Severity of psychiatric and physical problems is associated with lower quality of
      life in methadone patients in Indonesia.
AB  - BACKGROUND AND OBJECTIVES: The goal of methadone maintenance treatment (MMT) is
      to reduce the harm and to improve patients' quality of life (Qol). However, the
      Qol is also influenced by other co-occurring disorders. Data regarding the Qol
      and the co-occurrence of these disorders is lacking in low-middle income
      countries. We therefore describe the prevalence of physical, psychiatric, and
      drug abuse co-occurring disorders among MMT patients in Indonesia and determine
      the association between the severity of the co-occurring disorders and the Qol.
      METHODS: Data were collected in 112 injection drug abusers (IDUs) attending a MMT
      program in West Java, Indonesia, using validated questionnaires, medical records
      and laboratory testing. For comparison, 154 IDUs not enrolled in MMT were
      recruited by respondent driven sampling. RESULTS: The most frequent co-occurring
      disorders were hepatitis C (92%), HIV (77%), benzodiazepine abuse (56%), and
      anxiety disorders (32%). IDUs in MMT had one (26%), two (47%), or three (27%) co
      occurring disorders. Higher severity in psychiatric and physical problems was
      associated with poorer Qol. IDUs not enrolled in MMT had similar co-occurring
      problems. CONCLUSIONS: The prevalence of co-occurring disorders in IDUs in
      Indonesia is high and they influence their Qol. SCIENTIFIC SIGNIFICANCE:
      Therefore, comprehensive treatment, especially focusing on the common co
      occurring disorders should be provided in MMT to improve the Qol.

PMID- 23952887
TI  - Acceptability of contingency management among clinicians and clients within a co
      occurring mental health and substance use treatment program.
AB  - BACKGROUND: Emerging evidence supports the effectiveness of contingency
      management (CM) for addictions treatment among individuals with co-occurring
      serious mental illness (SMI). Addiction treatment for people with SMI generally
      occurs within community mental health centers (CMHCs) and it is not known whether
      CM is acceptable within this context. Client views regarding CM are also unknown.
      OBJECTIVES: This study is the first to describe CM acceptability among CMHC
      clinicians, and the first to explore client views. Clinician-level predictors of
      CM acceptability are also examined. METHODS: This study examined views about CM
      among 80 clinicians and 29 clients within a CMHC within the context of a
      concurrent CM study. RESULTS: Three-quarters of clinicians reported they would
      use CM if funding were available. Clinicians and clients affirmed that incentives
      enhance abstinence motivation. Clinician CM acceptability was related to greater
      years of experience, and identifying as an addictions or co-occurring disorders
      counselor, more than a mental health clinician. CONCLUSIONS: The findings provide
      preliminary evidence that CMHC clinicians, serving clients with addictions and
      complicating SMI, and client participants in CM, view CM as motivating and a
      positive tool to facilitate recovery. SCIENTIFIC SIGNIFICANCE: As an evidence
      based intervention, CM warrants further efforts toward funding and dissemination
      in CMHCs.

PMID- 23952888
TI  - A retrospective study of gender differences in depressive symptoms and risk of
      relapse in patients with alcohol dependence.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to investigate potential
      gender differences in situations associated with heavy alcohol drinking. METHODS:
      Data from 395 alcohol dependent patients participating in the Mayo Clinic
      Intensive Addiction Program were evaluated. Each participant completed the
      inventory of drug taking situations (IDTS), Penn alcohol craving scale (PACS),
      patient health questionnaire (PHQ-9), and/or Beck depression inventory (BDI).
      Gender differences in IDTS scores representing three domains (negative, positive,
      and temptation) of situations associated with heavy alcohol use were examined.
      RESULTS: Women with alcohol dependence report a higher frequency of heavy
      drinking in unpleasant emotional (IDTS negative scores mean +/- SD women vs. men:
      52.3 +/- 22.1 vs. 43.8 +/- 21.8; p = .0006), and as a result of temptation (IDTS
      temptation scores mean +/- SD women vs. men: 40.4 +/- 23.0 vs. 35.3 +/- 20.8; p =
      .035). Upon admission, women also scored significantly higher on depressive
      symptoms as measured by the BDI (23.4 +/- 11.4 vs. 18.2 +/- 9.8, p < .001). After
      controlling for depressive symptom severity as a covariate, the IDTS gender
      differences were no longer significant. CONCLUSION AND SCIENTIFIC SIGNIFICANCE:
      Our results suggest that unpleasant or temptation based emotional situations are
      a vulnerability risk factor for heavy drinking particularly in females. This risk
      appears to be at least partially driven by depressive symptom burden. Future
      research is needed to further investigate this finding.

PMID- 23952889
TI  - A double-blind placebo-controlled trial of N-acetylcysteine in the treatment of
      cocaine dependence.
AB  - BACKGROUND: There remains no FDA approved medication for the treatment of cocaine
      dependence. Preclinical studies and early pilot clinical investigations have
      suggested that N-acetylcysteine (NAC) may be useful in the treatment of the
      disorder. OBJECTIVE: The present report assessed the efficacy of NAC in the
      treatment of cocaine dependence. METHODS: Cocaine-dependent volunteers (n = 111)
      were randomized to receive daily doses of 1,200 mg of NAC, 2,400 mg of NAC, or
      placebo. Participants were followed for 8 weeks (up to three visits weekly). At
      each of these visits, urine samples were collected, along with self-reports of
      cocaine use. Urine samples were assessed for quantitative levels of
      benzoylecognine (ie, cocaine metabolite). RESULTS: Overall, the primary results
      for the clinical trial were negative. However, when considering only subjects who
      entered the trial having already achieved abstinence, results favored the 2,400
      mg NAC group relative to placebo, with the 2,400 mg group having longer times to
      relapse and lower craving ratings. CONCLUSION: While the present trial failed to
      demonstrate that NAC reduces cocaine use in cocaine-dependent individuals
      actively using, there was some evidence it prevented return to cocaine use in
      individuals who had already achieved abstinence from cocaine. SCIENTIFIC
      SIGNIFICANCE: N-acetylcysteine may be useful as a relapse prevention agent in
      abstinent cocaine-dependent individuals.

PMID- 23952890
TI  - Varenicline and neuronal nicotinic acetylcholine receptors: a new approach to the
      treatment of co-occurring alcohol and nicotine addiction?
AB  - BACKGROUND AND OBJECTIVES: Alcohol and nicotine dependence are serious public
      health problems worldwide. They are associated with substantial morbidity and
      mortality, as well as adverse social effects and increased healthcare costs.
      Although efficacious treatments are available for these disorders, additional
      therapeutic options are required to ensure greater treatment utilization. In this
      paper, we describe the empirical basis on which varenicline, a nicotinic partial
      agonist approved for smoking cessation, may also have utility in the treatment of
      alcohol addiction. METHODS: We sought to identify papers examining nicotine
      dependence, alcohol dependence, smoking, alcohol, and varenicline for possible
      inclusion in the present review. We identified over 600 papers through
      Pubmed/Medline, PsychINFO, and Google Scholar. We found 12 papers taking into
      consideration the following criteria: original language English, varenicline
      effect on alcohol consumption. RESULTS: Animal studies have shown that
      varenicline reduces alcohol consumption. Two recent studies showed that
      varenicline also reduces alcohol consumption in humans. Both nicotine and alcohol
      interact with alpha4beta2 and alpha3beta4 nicotinic acetylcholine (ACh) receptors
      located in the ventral tegmental area of the brain, inducing dopamine (DA)
      release at the nucleus accumbens. Varenicline binds to nicotinic ACh receptors,
      where it has partial agonist effects, producing a moderate and constant level of
      DA release both in the mesolimbic pathway and in the prefrontal cortex.
      CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Through these effects, varenicline may
      reduce alcohol craving, seeking, and consumption, in addition to promoting
      smoking cessation. Additional studies are needed to confirm the efficacy of
      varenicline in the treatment of alcohol dependence.

PMID- 23952891
TI  - Does exposure to parental substance use disorders increase substance use disorder
      risk in offspring? A 5-year follow-up study.
AB  - BACKGROUND: This study examined the impact of exposure to parental substance use
      disorders (SUD) (alcohol or drug abuse or dependence) on the development of SUD
      in offspring. METHODS: The original sample was derived from pediatric and
      psychiatric ascertained females 6-17 years old with (N = 140) and without
      Attention Deficit Hyperactivity Disorder (ADHD; N = 122). At baseline, these
      groups had 143 and 131 biological siblings and 274 and 238 parents, respectively.
      All subjects and their family members were comprehensively and blindly assessed
      by structured psychiatric interviews for psychopathology and substance use. The
      female probands and their siblings were reassessed after a follow-up period of 5
      years. RESULTS: At follow-up the mean age of offspring was 17.9 +/- 4.20 years.
      Independently of ADHD, familial risk, and socioeconomic status, exposure to
      maternal drug use disorders, but not paternal drug use disorders, was
      significantly associated with the development of a drug use disorder in offspring
      (OR: 7.04; p = 0.03). There was a significant association between exposure to
      parental SUD during adolescence (relative to preschool or latency years) and SUD
      in offspring (OR: 3.61; p = 0.03). CONCLUSIONS: Exposure to maternal drug use
      disorders during adolescent years increased the risk for the development of a
      drug use disorder in a sample of females with and without ADHD and their
      siblings. Exposure to parental SUD during adolescence specifically increases the
      risk of SUD development in offspring.

PMID- 23952892
TI  - Attention deficit hyperactivity disorder in cocaine-dependent adults: a
      psychiatric comorbidity analysis.
AB  - BACKGROUND AND OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is
      highly prevalent among drug abusers. We studied the psychiatric comorbidity and
      characteristics of cocaine use in relation to the presence of ADHD among patients
      with cocaine dependence. METHODS: A total of 200 cocaine-dependent patients
      attending an Outpatient Drug Clinic participated in the study. A systematic
      evaluation of ADHD (CAADID-II), the severity of addiction (EuropASI) and other
      axes I and II psychiatric disorders was made (SCID-I and SCID-II). A descriptive,
      bivariate, and multivariate analysis of the data was performed. RESULTS: In the
      multivariate analysis, the identified risk factors for the development of ADHD
      were a history of behavioral disorder in childhood (OR: 3.04), a lifetime history
      of cannabis dependence in the course of life (OR: 2.68), and age at the start of
      treatment (OR: 1.08). The bivariate analysis showed ADHD to be associated with
      other factors such as male gender, age at start of cocaine use and dependence,
      the amount of cocaine consumed weekly, increased occupational alteration, alcohol
      consumption, general psychological discomfort, depressive disorder, and
      antisocial personality disorder. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: We
      conclude that ADHD is associated with increased psychiatric comorbidity and
      greater severity of addiction.

PMID- 23952894
TI  - In vitro fertilization outcomes and alcohol consumption in at-risk drinkers: the
      effects of a randomized intervention.
AB  - BACKGROUND AND OBJECTIVES: Women's use of alcohol in pregnancy is associated with
      an increased risk of fetal loss and birth defects. Also, alcohol use in women
      decreases the success of infertility treatment, such as in vitro fertilization
      (IVF). Our goal was to determine if there were differences in IVF outcomes and
      alcohol use parameters among at-risk drinkers randomized to a brief intervention
      (BI) versus assessment only (AO). METHODS: We conducted a randomized controlled
      trial to determine the effect of BI or AO among at-risk drinkers on IVF. We
      studied 37 women (AO = 21; BI = 16). RESULTS: While the BI group had a
      significantly greater decrease in the number of drinks/drinking day compared to
      the AO group (p = .04), there were no differences in the likelihood of
      implantation failure, chemical pregnancy, spontaneous abortion, preterm birth, or
      live birth. CONCLUSIONS: BI and AO contributed to a decrease in alcohol use and
      did not demonstrate differences in IVF outcomes. A larger study may confirm these
      preliminary findings. SCIENTIFIC SIGNIFICANCE: Our results will assist care
      providers in treating alcohol use in pregnancy in an effective way, such that IVF
      cycles and the chance of pregnancy are optimized.

PMID- 23952893
TI  - Modeling the association between sexual maturation, transmissible risk, and peer
      relationships during childhood and adolescence on development of substance use
      disorder in young adulthood.
AB  - BACKGROUND: This prospective study investigated pubertal timing and transmissible
      risk in relation to affiliation with deviant peers on the development of
      substance use disorder (SUD). METHOD: Participants were boys (N = 500)
      ascertained through proband fathers with (N = 250), and without (N = 250) DSM-III
      R lifetime diagnosis of SUD who were prospectively tracked from age 10-12 to 22.
      Transmissible liability index (TLI), Tanner stage, peer delinquency, and
      substance use were measured at ages 10-12 and 16. SUD diagnosis during early
      adulthood was determined. RESULTS: Structural equation modeling revealed two
      pathways in which transmissible risk and sexual maturation influenced development
      of SUD. In the first pathway, transmissible risk was correlated with and
      prospectively predicted affiliation with deviant peers and substance use
      presaging SUD. In the second pathway, advanced sexual maturation positively
      predicted affiliation with deviant peers and substance use, which in turn
      predicted SUD. However, transmissible risk was not associated with pubertal
      development. CONCLUSION: These findings indicate that advanced sexual maturation
      and transmissible risk constitute unrelated facets of SUD liability; however,
      both factors bias development toward SUD via affiliation with deviant peers.
      SCIENTIFIC SIGNIFICANCE: Youth with advanced sexual maturation and/or
      transmissible risk for SUD are at higher risk for developing SUD. Additional
      research is needed to determine if addressing these risk factors will contribute
      to advancements in SUD prevention.

PMID- 23952896
TI  - Decision-making deficits in pathological gambling: the role of executive
      functions, explicit knowledge and impulsivity in relation to decisions made under
      ambiguity and risk.
AB  - BACKGROUND: A variety of cognitive and emotional processes influence the decision
      making deficits observed in pathological gambling (PG). This study investigated
      the role of immediate/delayed sensitivity to reward and punishment, executive
      functions, impulsivity and explicit knowledge in relation to decision-making
      performance on the original Iowa Gambling Task (IGT-ABCD) and a variant (IGT
      EFGH). METHODS: We assessed 131 consecutive patients with a diagnosis of PG by
      using executive functioning and decision-making tasks, self-report measures of
      impulsivity and explicit knowledge. RESULTS: The majority of pathological
      gamblers (PGs) showed deficits in decision-making, characterized mainly by myopia
      for the future. Decisions made under risk showed different predictors.
      Performance on the IGT-ABCD for decisions made under risk was predicted by medium
      and high levels of explicit knowledge of the task, as well as by scores on the
      Disorderliness subscale and the degree of Stroop interference. By contrast, IGT
      EFGH results were only associated with self-report impulsivity measures.
      CONCLUSIONS: Decision making in PG involves distinct patterns of deficits, and
      the predictors differ depending on the reinforcement schedule. Decisions made
      under risk on the IGT-ABCD are associated with explicit knowledge, executive
      functions and impulsivity traits related to conscious awareness and control
      processes. On the IGT-EFGH, however, only impulsivity traits predict decision
      making.

PMID- 23952895
TI  - Pain and motives for use among non-treatment seeking individuals with
      prescription opioid dependence.
AB  - BACKGROUND AND OBJECTIVES: Patients with prescription opioid use disorders and co
      occurring pain present a formidable challenge for healthcare providers, and
      little is known about patients with this dual diagnosis. This study examined the
      prevalence of pain and motives for use among individuals with prescription opioid
      dependence. METHODS: Participants (N = 127) included 86 non-treatment seeking
      individuals with current prescription opioid dependence and 41 healthy controls.
      They were administered a battery of assessments to evaluate pain and substance
      use. RESULTS: Participants with prescription opioid dependence were significantly
      more likely than controls to report current pain (62.2 vs. 12.2%), as well as
      higher levels of pain interference and severity. The most common source of
      prescription opioids was a physician (91.3%) and the most common motive for using
      prescription opioids, initially and currently, was to relieve pain (70.3% and
      81.0%, respectively). Motivation for subsequent non-medical use of prescription
      opioids included to get high (73.8%), to increase energy (71.0%), to decrease
      anxiety (51.2%), and to improve sleep (35.7%). CONCLUSION: Pain is a significant
      comorbidity and motivator for the non-medical use of prescription opioids.
      Provider and patient education regarding the safe use of prescription opioids, as
      well as interventions targeting prescription opioid dependence, are needed.

PMID- 23952897
TI  - Community-based treatment for opioid dependent offenders: a pilot study.
AB  - BACKGROUND: Primary care opioid substitution treatment (OST) has not been
      compared to program-based OST for community-supervised offenders. OBJECTIVE: The
      purpose of this project was to compare primary care to specialist supervised OST
      for opioid dependent offenders in terms of substance use and HIV risk outcomes.
      METHODS: This project randomly assigned 15 jail diversion participants to either:
      (i) primary care buprenorphine OST, (ii) specialist facility buprenorphine OST,
      or (iii) specialist facility methadone OST. Participation lasted 13.5 months (12
      month active treatment plus a post-participation visit). RESULTS: All subjects
      endorsed 0 days of opioid use in the previous 14 at follow-up. Specialty care
      reduced HIV risk (Risk Assessment Battery composite score) over 6 months (-.24 +/
      .17) compared to primary care (.02 +/- .14; p = .032). CONCLUSION: Findings
      support primary care OST feasibility for a community-supervised offender sample.
      Specialist care may facilitate improvements in secondary outcomes, such as HIV
      risk behaviors. SCIENTIFIC SIGNIFICANCE: Further research is needed to clarify
      (i) the role of primary care in addicted offender management, and (ii) the
      matching of offenders, based upon history and co-morbidity, to care coordination
      conditions.

PMID- 23952898
TI  - Symptom profile and outcome of delirium associated with alcohol withdrawal
      syndrome: a study from India.
AB  - AIM: To study the profile of delirium associated with alcohol withdrawal syndrome
      (AWS) in a developing country in terms of symptomatology, associated risk
      factors/physical complications, and outcome. METHODOLOGY: Using a prospective
      design, 112 patients in whom delirium could be attributed to AWS as either the
      sole or a contributory cause were assessed by Delirium Rating Scale-Revised-98
      and the associated etiological factors were assessed by using delirium etiology
      checklist. FINDINGS: In all patients, delirium was acute in onset and all
      patients had disturbance of sleep-wake cycle and inattention. Other common
      symptoms were: disorientation (99.1%), fluctuation in symptoms (97.3%), motor
      agitation (94.6%), and short-term memory disturbance (92.9%). In terms of
      delirium etiology checklist etiological categories, besides alcohol withdrawal,
      the most common factors were metabolic/endocrine abnormalities (76%), followed by
      organ insufficiency and infection (37% and 35%, respectively). Most patients
      (67%) improved or recovered completely from delirium during the short stay of 4
      days. During the short stay of mean duration of 4 days 13.4% of the patients died
      during the hospital stay. CONCLUSION: Delirium associated with alcohol withdrawal
      is characterized by an acute onset of symptoms with high prevalence of
      disturbance of sleep-wake cycle, inattention, disorientation, fluctuation in
      symptoms, motor agitation, and disturbance in short-term memory. There are
      certain differences in the symptom profile of delirium associated with alcohol
      withdrawal and that associated with medical-surgical causes. About one-sixth of
      the patients developing delirium due to alcohol withdrawal die during the short
      hospital stay of 4 days.

PMID- 23952899
TI  - Around-the-clock oral THC effects on sleep in male chronic daily cannabis
      smokers.
AB  - BACKGROUND AND OBJECTIVES: Delta9-tetrahydrocannabinol (THC) promotes sleep in
      animals; clinical use of THC is associated with somnolence. Human laboratory
      studies of oral THC have not shown consistent effects on sleep. We prospectively
      evaluated self-reported sleep parameters during controlled oral THC
      administration to research volunteers. METHODS: Thirteen male chronic daily
      cannabis smokers (mean +/- SD age 24.6+/- 3.7 years, self-reported smoking
      frequency of 5.5 +/- 5.9 (range 1-24) joint-equivalents daily at study entry)
      were administered oral THC doses (20 mg) around-the-clock for 7 days (40-120 mg
      daily) starting the afternoon after admission. The St. Mary's Hospital Sleep
      Questionnaire was completed every morning. Plasma THC and 11-OH-THC (active
      metabolite) concentrations were measured in venous blood samples collected every
      evening. Changes in sleep characteristics over time and associations between
      sleep characteristics and plasma cannabinoid concentrations were evaluated with
      repeated measures mixed linear regression. RESULTS: Higher evening THC and 11-OH
      THC concentrations were significantly associated with shorter sleep latency, less
      difficulty falling asleep, and more daytime sleep the following day. In contrast,
      the duration of calculated and self-reported nighttime sleep decreased slightly
      (3.54 and 5.34 minutes per night, respectively) but significantly during the
      study. CONCLUSIONS: These findings suggest that tolerance to the somnolent
      effects of THC may have occurred, but results should be considered preliminary
      due to design limitations. SCIENTIFIC SIGNIFICANCE: Somnolence from oral THC may
      dissipate with chronic, high-dose use. This has implications for patients who may
      take chronic oral THC for medicinal purposes, including cannabis dependence
      treatment. (Am J Addict 2013;22:510-514).

PMID- 23952900
TI  - Characteristics of medical inpatients with acute pain and suspected non-medical
      use of opioids.
AB  - OBJECTIVE: The purpose of this study was to characterize medical inpatients with
      acute pain suspected of non-medical opioid use. METHOD: Medical inpatients
      treated with opioids for acute pain referred for psychiatric consultation were
      administered questionnaires including the Screener and Opioid Assessment for Pain
      Patients (SOAPP) and the Hospital Misuse Checklist (HMC), developed for this
      study. RESULTS: The nine subjects referred for evaluation of possible non-medical
      opioid use, compared to the 23 subjects referred for other reasons, were younger
      (37.7 vs. 51.3, t = 2.81, p = .012), more likely to score positive on the SOAPP
      (100% vs. 47.8%, Fisher's p < .05) and report lifetime histories of any substance
      use disorder (SUD) (88.9% vs. 30.4%, chi2  = 9.7, p = .002). No differences were
      found on items on the HMC. CONCLUSIONS: The results of this preliminary study
      indicate that medical inpatients with suspected non-medical use of opioids
      resemble chronic pain outpatients misusing opioids. Further research is needed to
      better characterize this patient population and to validate the HMC measure.

PMID- 23952902
TI  - Formation of the SiP radical through radiative association.
AB  - Formation of the SiP radical through radiative association of Si((3)P) and
      P((4)S) atoms is studied using classical and quantum dynamics. Rate coefficients
      for formation in the two lowest doublet states and the two lowest quartet states
      are calculated for T = 10-20,000 K. Breit-Wigner theory is used to properly
      account for contribution from quantum mechanical resonances.

PMID- 23952901
TI  - Stress-related biomarkers of dream recall and implicit memory under anaesthesia.
AB  - The aim of this study was to investigate whether auditory presentation of a story
      during general anaesthesia might influence stress hormone changes and thus
      affecting dream recall and/or implicit memory. One hundred and ten patients were
      randomly assigned either to hear a recording of a story through headphones or to
      have routine care with no auditory recording while undergoing laparoscopic
      cholecystectomy. Anaesthesia was standardised. Blood samples for cortisol and
      prolactin assays were collected 20 min before anaesthesia and 5 min after
      pneumoperitoneum. Dream recall and explicit/implicit memory were investigated
      upon awakening from anaesthesia and approximately 24 h after the end of the
      operation. Auditory presentation was associated with lower intra-operative serum
      prolactin concentration compared with control (p = 0.0006). Twenty-seven patients
      with recall of dreaming showed higher intra-operative prolactin (p = 0.004) and
      lower cortisol (p = 0.03) concentrations compared with those without dream
      recall. The knowledge of this interaction might be useful in the quest to ensure
      postoperative amnesia.

PMID- 23952903
TI  - Management of hypertension in adults: the 2013 French Society of Hypertension
      guidelines.
AB  - To improve the management of hypertension in the French population, the French
      Society of Hypertension has decided to issue a new set of guidelines that include
      the following practical characteristics: usefulness for clinical practice, short,
      easy-to-read format, comprehensive writing for non-physicians, wide dissemination
      among healthcare professionals and the hypertensive population, assessment of
      their impact among healthcare professionals and with regard to public health
      goals. These guidelines, so-called the appointments of the hypertensive patient,
      include 15 recommendations, divided into three chapters, according to the timing
      of the medical management: prior to treatment initiation, the initial treatment
      plan (first 6 months) and the long-term care plan (beyond 6 months). We hope that
      a vast dissemination of these simple guidelines will help to improve hypertension
      control in the French population from 50% to 70%, an objective expected to be
      achieved in 2015 in France.

PMID- 23952904
TI  - Post-translational regulation of gene expression using the ATF4 oxygen-dependent
      degradation domain for hypoxia-specific gene therapy.
AB  - Solid tumors have hypoxic regions in their cores, due to low blood supply levels.
      Therefore, hypoxia-specific gene regulation systems have been developed for tumor
      specific gene therapy. In this study, the oxygen-dependent degradation (ODD)
      domain on activating transcription factor-4 (ATF4) was evaluated for post
      translational regulation of proteins. The ATF4 ODD cDNA was amplified by RT-PCR,
      and a luciferase plasmid containing the ATF4 ODD domain, pSV-Luc-ATF4-ODD, was
      constructed. Luciferase expression was induced under hypoxia by the ATF4 ODD
      domain in transfection assays into N2A neuroblastoma cells, C6 glioblastoma
      cells, and U87 glioblastoma cells. In the transfection assay with pSV-Luc-ATF4
      ODD, RT-PCR results showed that the mRNA level did not change under hypoxia. This
      suggests that the induction of luciferase under hypoxia was mediated by post
      translational regulation. A plasmid expressing thymidine kinase from herpes
      simplex virus (HSV-tk), pSV-HSVtk-ATF4-ODD, was constructed with the ATF4 ODD
      cDNA. The transfection assay with pSV-TK-ATF4-ODD showed that the ATF4 ODD domain
      induced HSV-tk expression under hypoxia and facilitated the death of C6 cells in
      the presence of ganciclovir (GCV). Furthermore, pSV-HSVtk-ATF4-ODD induced
      caspase-3 activity in the hypoxic cells. In conclusion, the ATF4 ODD may be
      useful for hypoxia-specific gene therapy by post-translational regulation of gene
      expression.

PMID- 23952905
TI  - Histone deacetylase SIRT1 modulates and deacetylates DNA base excision repair
      enzyme thymine DNA glycosylase.
AB  - TDG (thymine DNA glycosylase) is an essential multifunctional enzyme involved in
      DNA base excision repair, DNA demethylation and transcription regulation. TDG is
      the predominant enzyme that removes thymine from T/G mispair, which arises due to
      deamination of 5-methyl-cytosine at the CpG dinucleotide, thereby preventing C to
      T mutations. SIRT1 is a member of class III NAD+-dependent histone/protein
      deacetylases. In the present study, we demonstrate that SIRT1 interacts with
      residues 67-110 of hTDG (human TDG). In addition, SIRT1 enhances TDG glycosylase
      activity and deacetylates acetylated TDG. TDG acetylation weakens its interaction
      with SIRT1. Although acetylated TDG has reduced glycosylase activity towards T/G,
      5-formylcytosine/G and 5-carboxylcytosine/G, it has a stronger activity towards a
      5-fluorouracil/G substrate as compared with unmodified TDG. SIRT1 weakly
      stimulates acetylated hTDG activity towards T/G, 5-formylcytosine/G and 5
      carboxylcytosine/G as compared with control hTDG. Sirt1-knockout mouse embryonic
      fibroblast cells have higher levels of TDG expression and acetylation. The
      physical and functional interactions between SIRT1 and TDG may mediate DNA
      repair, gene expression and FU (5-fluorouracil)-mediated cytotoxicity. 

PMID- 23952906
TI  - Comparison of trichiasis recurrence after primary bilamellar tarsal rotation or
      anterior lamellar repositioning surgery performed for trachoma.
AB  - BACKGROUND: To compare the trichiasis recurrence rate following bilamellar tarsal
      rotation or anterior lamellar repositioning, performed as primary surgery for
      trachomatous trichiasis. DESIGN: Retrospective consecutive case series.
      PARTICIPANTS: All cases of trachomatous trichiasis undergoing primary surgical
      correction at Alice Springs Hospital, Alice Springs, Northern Territory,
      Australia, between 1 June 2001 and 11 June 2011 were included. METHODS:
      Retrospective chart review. Key baseline, operative and outcome details were
      collected from the notes. MAIN OUTCOME MEASURE: Recurrent trichiasis was defined
      as one or more lashes touching the cornea, resulting in recurrent symptoms of
      trichiasis and warranting further surgery in the opinion of the treating
      ophthalmologist. RESULTS: Sixty-seven BTR and eighteen ALR procedures were
      performed, with BTR being performed from 2001 to 2008, and ALR from 2008 to 2011.
      The mean follow-up times were significantly different for the BTR group (1654
      days) and for the ALR group (673 days)(P < 0.001). Kaplan-Meier survival analysis
      did not reveal any significant differences in recurrence rate between the two
      procedures overall (P = 0.935). Analysis of the 2008 calendar year (the only year
      where both procedures were performed and therefore had equal follow-up times)
      suggested that ALR might have a lower recurrence rate (1/10 ALR recurrences vs.
      4/6 BTR recurrences, P = 0.181). CONCLUSIONS: The results do not demonstrate a
      difference in the recurrence rate between the two techniques. Inconsistent follow
      times however leave uncertainty in this result, and a larger prospective
      randomised study is warranted to address this question.

PMID- 23952907
TI  - A controlled study of suicide in middle-aged and older people: personality
      traits, age, and psychiatric disorders.
AB  - Personality traits were examined using the NEO Five-Factor Inventory-Revised in
      an Australian psychological autopsy study involving 259 suicide deaths and 181
      sudden death controls aged 35 years and over. Interviews included the Structured
      Clinical Interview for DSM-IV to determine the presence of psychiatric disorder.
      Personality traits of suicide deaths differed significantly from those of
      controls, scoring higher in the Neuroticism and Openness to Experience domains
      and lower on the Agreeableness and Extraversion domains. These findings varied
      with the presence of psychiatric disorder and by age. High Neuroticism scores
      were the most consistent finding in people who died by suicide, although these
      scores decreased in older suicides. 

PMID- 23952908
TI  - Characterization of biological aerosol exposure risks from automobile air
      conditioning system.
AB  - Although use of automobile air conditioning (AC) was shown to reduce in-vehicle
      particle levels, the characterization of its microbial aerosol exposure risks is
      lacking. Here, both AC and engine filter dust samples were collected from 30
      automobiles in four different geographical locations in China. Biological
      contents (bacteria, fungi, and endotoxin) were studied using culturing, high
      throughput gene sequence, and Limulus amebocyte lysate (LAL) methods. In-vehicle
      viable bioaerosol concentrations were directly monitored using an ultraviolet
      aerodynamic particle sizer (UVAPS) before and after use of AC for 5, 10, and 15
      min. Regardless of locations, the vehicle AC filter dusts were found to be laden
      with high levels of bacteria (up to 26,150 CFU/mg), fungi (up to 1287 CFU/mg),
      and endotoxin (up to 5527 EU/mg). More than 400 unique bacterial species,
      including human opportunistic pathogens, were detected in the filter dusts. In
      addition, allergenic fungal species were also found abundant. Surprisingly,
      unexpected fluorescent peaks around 2.5 MUm were observed during the first 5 min
      use of AC, which was attributed to the reaerosolization of those filter-borne
      microbial agents. The information obtained here can assist in minimizing or
      preventing the respiratory allergy or infection risk from the use of automobile
      AC system.

PMID- 23952909
TI  - Reticular Erythematous Mucinosis in an atypical pattern distribution responds to
      UVA1 phototherapy.

PMID- 23952910
TI  - Artificial neural network techniques to improve the ability of optical coherence
      tomography to detect optic neuritis.
AB  - PURPOSE: To analyze the ability of Spectralis optical coherence tomography (OCT)
      to detect multiple sclerosis (MS) and to distinguish MS eyes with antecedent
      optic neuritis (ON). To analyze the capability of artificial neural network (ANN)
      techniques to improve the diagnostic precision. METHODS: MS patients and controls
      were enrolled (n = 217). OCT was used to determine the 768 retinal nerve fiber
      layer thicknesses. Sensitivity and specificity were evaluated to test the ability
      of OCT to discriminate between MS and healthy eyes, and between MS with and
      without antecedent ON using ANN. RESULTS: Using ANN technique multilayer
      perceptrons, OCT could detect MS with a sensitivity of 89.3%, a specificity of
      87.6%, and a diagnostic precision of 88.5%. Compared with the OCT-provided
      parameters, the ANN had a better sensitivity-specificity balance. CONCLUSIONS:
      ANN technique improves the capability of Spectralis OCT to detect MS disease and
      to distinguish MS eyes with or without antecedent ON.

PMID- 23952912
TI  - Mixed AggregAte (MAA): a single concept for all dipolar organometallic
      aggregates. 2. Syntheses and reactivities of homo/heteroMAAs.

PMID- 23952911
TI  - The effect of intravitreal anti-VEGF on the pigment epithelial detachment in eyes
      with the exudative type of age-related macular degeneration.
AB  - PURPOSE: To evaluate the effect of anti-VEGF treatment on pigment epithelial
      detachment (PED) secondary to the exudative type of age-related macular
      degeneration (AMD). METHODS: Retrospective analysis of 30 eyes (28 patients) with
      exudative AMD accompanied by PED (receiving anti-VEGF injections). Alterations of
      the PED morphology were qualitatively assessed with optical coherence tomography
      (OCT). Changes in best-corrected visual acuity (BCVA) and number of injections
      were compared to 30 control eyes (30 patients) exhibiting exudative AMD without
      PED. RESULTS: Mean follow-up was 19.8 months. Changes of the extent of PED were
      as follows: unchanged: 11 eyes (36.7%); reduced: 12 (40%); significantly reduced:
      7 (23.3%). Mean paired difference in BCVA was -0.08 logMAR (p = 0.46) and in the
      number of injections was 2.1 injections (p = 0.04). CONCLUSIONS: A substantial
      number of the studied patients showed reduction of the extent of the PED after
      anti-VEGF treatment. The PED group required a higher number of injections.

PMID- 23952913
TI  - A geometric approach to study the contact mechanisms in the patellofemoral joint
      of normal versus patellofemoral pain syndrome subjects.
AB  - The biomechanics of the patellofemoral (PF) joint is complex in nature, and the
      aetiology of such manifestations of PF instability as patellofemoral pain
      syndrome (PFPS) is still unclear. At this point, the particular factors affecting
      PFPS have not yet been determined. This study has two objectives: (1) The first
      is to develop an alternative geometric method using a three-dimensional (3D)
      registration technique and linear mapping to investigate the PF joint contact
      stress using an indirect measure: the depth of virtual penetration (PD) of the
      patellar cartilage surface into the femoral cartilage surface. (2) The second is
      to develop 3D PF joint models using the finite element analysis (FEA) to quantify
      in vivo cartilage contact stress and to compare the peak contact stress location
      obtained from the FE models with the location of the maximum PD. Magnetic
      resonance images of healthy and PFPS subjects at knee flexion angles of 15
      degrees , 30 degrees  and 45 degrees  during isometric loading have been used to
      develop the geometric models. The results obtained from both approaches
      demonstrated that the subjects with PFPS show higher PD and contact stresses than
      the normal subjects. Maximum stress and PD increase with flexion angle, and occur
      on the lateral side in healthy and on the medial side in PFPS subjects. It has
      been concluded that the alternative geometric method is reliable in addition to
      being computationally efficient compared with FEA, and has the potential to
      assess the mechanics of PFPS with an accuracy similar to the FEA.

PMID- 23952915
TI  - Correlated charge carrier-like photoresponse of polymer nanowires.
AB  - Size confinement at nanometer length scales gives rise to many new and tunable
      properties of organic materials that are absent in their bulk state. Here we
      report, the appearance of large photoconduction property of a conducting polymer
      when it forms nanowires. The photoresponse and the external photoconductive gain
      were found to be >10(5) % and >200%, respectively, even at low bias (<1 V)
      voltage. These nanowires show a resistance switching transition at low
      temperature above a threshold bias, and below this transition, the resistance
      changes by more than 3 orders of magnitude under illumination of light. The
      photoresponse increases superlinearly and the resistance switching threshold
      voltage decreases with increasing illumination intensity. These properties are
      absent in the bulk polymer, and the observed photoresponse is not bolometric or
      excitonic in nature, nor it can be explained by free carrier generation or
      Schottky barrier modulation, rather it is consistent with the photoexcitation of
      correlated charge carriers. 

PMID- 23952914
TI  - Detection and molecular characterization of infectious spleen and kidney necrosis
      virus from major ornamental fish breeding states in Peninsular Malaysia.
AB  - 'Gold standard' OIE reference PCR assay was utilized to detect the presence of
      infectious spleen and kidney necrosis virus (ISKNV) in freshwater ornamental fish
      from Malaysia. From total of 210 ornamental fish samples representing 14 species,
      ISKNV was detected in 36 samples representing 5 fish species. All positive cases
      did not show any clinical signs of ISKNV. Three restriction enzymes analyses
      showed that the fish were infected by identical strains of the same virus species
      within Megalocytivirus genus. Major capsid protein (MCP) genes of 10 ISKNV
      strains were sequenced and compared with 9 other reference nucleotide sequences
      acquired from GenBank. Sequence analysis of MCP gene showed that all strains
      detected in this study were closely related to the reference ISKNV with
      nucleotide sequence identity that was ranging from 99.8% to 100%. In addition,
      phylogenetic analysis of MCP gene revealed that viruses from genus
      Megalocytivirus can be divided into three genotypes: genotype 1 include reference
      ISKNV and all other strains that were detected in this study, genotype 2 include
      viruses closely related to red sea bream iridovirus (RSIV), and genotype 3
      include viruses closely related turbot reddish body iridovirus (TRBIV). 

PMID- 23952916
TI  - Vinyl sulfone-based peptidomimetics as anti-trypanosomal agents: design,
      synthesis, biological and computational evaluation.
AB  - A series of vinyl sulfone-containing peptidomimetics were rationally designed,
      synthesized, and evaluated against Trypanosoma brucei brucei . These
      electrophilic compounds are likely to exert their antitrypanosomal activity via
      inhibition of trypanosomal cysteine proteases, TbCatB and rhodesain, through
      alkylation of a key cysteine residue within the protease active site. The series
      was designed to present complementary groups to naturally recognized peptide
      substrates while probing tolerance to a range of substitutions at the P1, P1',
      and P2 positions. The most potent compound, 29 (EC50 = 70 nM, T. b. brucei whole
      cell assay), displayed minimal toxicity (>785 times selectivity) when assayed for
      cytotoxicity against the human promyelocytic leukemia (HL-60) cell line. Cells
      treated with compound 29, as with K777 (2), exhibited an increase in both the
      number of multinucleated cells and cells with swollen flagellar pockets.
      Computational analysis revealed a strong correlation between the hypothetical
      binding mode in TbCatB/rhodesain and trypanocidal activity in vitro. 

PMID- 23952917
TI  - Effect of 'activity monitor-based' counseling on physical activity and health
      related outcomes in patients with chronic diseases: A systematic review and meta
      analysis.
AB  - AIM: This review evaluated the effects of activity monitor-based counseling on
      physical activity (PA) and generic and disease-specific health-related outcomes
      in adults with diabetes mellitus type II (DMII), chronic obstructive pulmonary
      disease (COPD), or chronic heart failure (CHF). METHODS: Four electronic
      databases were searched for randomized controlled trials using activity monitor
      based counseling versus control intervention or usual care in adults with DMII,
      COPD, or CHF. Pooled effect sizes were calculated using a random effects model.
      RESULTS: Twenty-four articles were included: 21 DMII studies and 3 COPD studies.
      No CHF studies were identified. Pooled analysis showed that activity monitor
      based counseling resulted in a significantly greater improvement in PA compared
      to control intervention or usual care in DMII. Furthermore, these interventions
      had a beneficial effect on hemoglobin A1c (HbA1c), systolic blood pressure, and
      body mass index (BMI) (P < 0.05), whereas no differences were found on diastolic
      blood pressure, and health-related quality of life. Meta-analysis of COPD studies
      was not possible due to lack of available data. CONCLUSION: Activity monitor
      based counseling had a beneficial effect on PA, HbA1c, systolic blood pressure,
      and BMI in patients with DMII. Data in patients with COPD and CHF are limited or
      non-existing, respectively.

PMID- 23952918
TI  - Fatty acids as determinants of in-vivo lipid peroxidation: the EFFGE study in
      Eastern Finnish hypertensive and non-hypertensive subjects.
AB  - BACKGROUND: The degree of fatty acid (FA) unsaturation as a determinant of lipid
      peroxidation has been inadequately studied. METHODS: We examined associations of
      plasma free F2alpha-isoprostanes (F2-IsoPs), an indicator of in-vivo lipid
      peroxidation, with the levels/intake of FAs, adjusted for the risk factors of
      cardiovascular disease (CVD) in 1211 Finnish men and women, of whom 50% were
      hypertensive, aged 59.3 +/- 8.3 years, mean +/- SD. RESULTS: Elevated age- and
      sex-adjusted plasma free levels of omega-6 and omega-3 polyunsaturated Fas
      (PUFAs), saturated FAs (SFAs), and the PUFA/SFA and the omega-6/omega-3 PUFA
      ratios were all associated with decreased F2-IsoPs. High dietary SFA intake was
      associated with elevated F2-IsoP concentrations. In a multivariable regression
      (with clinical, nutritional, and behavioral CVD risk factors), female gender,
      body mass index (BMI), serum apolipoprotein A1, and NT-proBNP (natriuretic
      peptide) were positively associated with the F2-IsoPs, whereas the dietary
      PUFA/SFA ratio, plasma beta-carotene, the omega-6/omega-3 PUFA ratio, and protein
      intake showed inverse associations. CONCLUSIONS: We propose that elevated lipid
      peroxidation is associated with several risk factors of CVD, such as a low
      PUFA/SFA ratio, whereas the FA precursors of lipid peroxidation, i.e. omega-3 and
      omega-6 PUFAs are associated with attenuated F2-IsoP levels. These findings
      provide mechanistic support for earlier observations linking PUFA to improved
      cardiovascular health.

PMID- 23952919
TI  - Investigating support needs for people living with heart disease.
AB  - AIM AND OBJECTIVES: To identify the issues that required ongoing support for
      people who have completed a cardiac rehabilitation programme. BACKGROUND:
      Surviving a serious cardiac event is a stressful and traumatic experience, often
      resulting in major changes in a person's lifestyle, work, finances and family
      dynamics. Individuals who have experienced a cardiac event and completed a
      cardiac rehabilitation programme may require ongoing support. The issues
      requiring support are unclear. DESIGN: A qualitative, descriptive study. METHODS:
      Nine participants, who were at least four weeks postcompletion of a cardiac
      rehabilitation programme, were interviewed. Data were collected using semi
      structured interviews and analysed using thematic analysis. RESULTS: The
      participants in this project clearly articulated that informational,
      psychological and social supports were imperative in enabling recovery from a
      serious cardiac event. Even though participation in a cardiac rehabilitation
      programme is seen as being very valuable, there is a need for ongoing support to
      absorb shock, maintain lifestyle changes and navigate a new way of life.
      CONCLUSIONS: This study highlights the gap in ongoing support for people
      postparticipation in cardiac rehabilitation programmes and the need for different
      levels of support during their recovery. Agencies such as Heart Foundation are
      well placed to facilitate connections between people living with heart disease
      and available support programmes and services. Initiatives that link individuals
      to community-run, peer-led support groups, walking and exercise programmes would
      be especially valuable. RELEVANCE TO CLINICAL PRACTICE: Individuals who have
      experienced an acute cardiac event need ongoing support across the recovery
      continuum. Consideration needs to be given to care models that address this need
      including exploring the potential of peer support.

PMID- 23952921
TI  - Understanding the role of National Public Health Surveys in identifying health
      care disparities affecting LGBT people.

PMID- 23952920
TI  - Beta-amyloid oligomer.

PMID- 23952922
TI  - Does place of residence matter? Rural-urban differences and the wellbeing of gay
      men and lesbians.
AB  - Does place of residence matter for gay men and lesbians? Both conventional wisdom
      and scholarly literature suggests that it does, and that those living in rural
      areas are disadvantaged relative to their urban peers. This study explores this
      issue by comparing gay people's wellbeing in rural and urban areas. Results from
      a large probability sample show that rural gay people fare no worse than their
      urban peers. If anything, results suggest living in the largest cities may be
      detrimental to gay people's wellbeing, although more so for lesbians than for gay
      men. Results are discussed in light of 4 competing perspectives on rural-urban
      differences.

PMID- 23952923
TI  - Online networks as a venue for social support: a qualitative study of married
      bisexual men in Taiwan.
AB  - Online networks have become a critical venue for bisexual males to communicate
      with each other and solicit social support. This study reports qualitative
      feedback gathered from 12 married Taiwanese bisexual men about online social
      support in their daily lives. The analysis of interviews reveal that online
      social support provides participants with opportunities to screen potential
      friends, participate in the bisexual virtual community, come out and release
      stress, and look for romance. Apparently, for married bisexual men in Taiwan, the
      Internet offers an opportunity to anonymously manage sexual identity and solicit
      social support among other bisexuals. 

PMID- 23952924
TI  - Correlates of homophobia, transphobia, and internalized homophobia in gay or
      lesbian and heterosexual samples.
AB  - This research assessed the correlates of homophobia and transphobia in
      heterosexual and homosexual individuals, based on a theory of different sources
      of perceived symbolic threat to social status. Compared to 310 heterosexual
      college students, a sample of 30 gay male and 30 lesbian college students scored
      lower on homophobia, transphobia, and religious fundamentalism. Mean gender
      differences were smaller for gay men and lesbians for homophobia, aggressiveness,
      benevolent sexism, masculinity, and femininity. Fundamentalism, right-wing
      authoritarianism, and hostile and benevolent sexism were correlated only with
      homophobia in lesbians, whereas fundamentalism and authoritarianism were
      correlated only with transphobia in gay men. Correlates of internalized
      homophobia were different than those found for homophobia and transphobia, which
      was discussed in terms of gender differences in threats to status based on sexual
      orientation versus gender identity.

PMID- 23952925
TI  - Sexual identity in the American Deep South: the concordance and discordance of
      sexual activity, relationships, and identities.
AB  - This research explores the association between sexual identity and sexual
      behavior and how that association varies across gender and race in the American
      Deep South. Multinomial logistic regression analysis is used to determine the
      likelihood of each sexual identity given past sexual behavior, sexual
      relationships, and other social characteristics. The more traditional cultural
      climate of the South appears to suppress identification as a sexual minority.
      Sexual identification in the Deep South is primarily a product of sexual activity
      and sexual relationships, although attitudes toward and contact with the lesbian,
      gay, bisexual, and transgender (LGBT) community play a minor role. Although most
      participants' sexual behaviors and identities were in concordance, sexual
      discordance was highest for White women and lowest for White men. Discordance was
      also associated with traditional men's roles attitudes, negative homosexuality
      attitudes, and contact with the LGBT community. It is hoped that these results
      encourage scholarship that deconstructs the sexual behavior and identity of all
      groups, not just oppressed groups.

PMID- 23952926
TI  - Queer eye for the straight guy: sexual orientation and stereotype lift effects on
      performance in the fashion domain.
AB  - Stereotype lift is defined as a boost in performance caused by an awareness of a
      positive ingroup stereotype. This study investigated if gay men experience
      stereotype lift in the fashion domain. To date, no studies have examined
      stereotype lift in regards to stereotypes about sexual orientation or in regards
      to a non-academic task. To address this gap in the literature, gay and straight
      men completed a test of fashion knowledge under conditions where the relevant gay
      stereotype was either salient or not by reminding participants of their sexual
      orientation before or after completing the test. A sample of 66 undergraduate
      male students (31 heterosexual and 35 homosexual) showed that gay men did
      outperform straight men on the fashion test, but only when the relevant
      stereotype was made salient, F(1, 62) = 5.23, p = .03. Implications of stereotype
      lift in gay men and on non-academic tasks are discussed.

PMID- 23952927
TI  - Attitudes toward same-sex marriage: the case of Scandinavia.
AB  - The purpose of this study was to examine the variables that explain attitudes
      toward same-sex marriage. Using recently collected Scandinavian data (from Norway
      and Sweden) with a high response rate, this study shows that gender, regular
      participation in religious activities, political ideology, education, whether the
      respondent lived in the capital city, and attitudes toward gender equality were
      important for attitudes toward same-sex marriage. Age and income were not
      important for attitudes toward same-sex marriage. Although both Norwegians and
      Swedes clearly favor same-sex marriage, Swedes are significantly more positive
      than Norwegians.

PMID- 23952929
TI  - Catalytic enantioselective dibromination of allylic alcohols.
AB  - A new dibromination reaction involving the combination of dibromomalonate as the
      bromonium source and a titanium bromide species as the bromide source has been
      developed. Enantioselective catalysis has been achieved through apparent ligand
      acceleration by a tartaric acid-derived diol. 

PMID- 23952932
TI  - Achieving occupational role: accommodations for students with disability.
AB  - The purpose of this paper is to describe background and strategies utilized by
      occupational therapy educators in conjunction with Disabled Students Services
      personnel and students with disabilities to effect academic accommodations that
      will enhance their chances for success in academia and subsequently in the
      practice of occupational therapy. 

PMID- 23952930
TI  - Effects of cyclosporine a in ex vivo reperfused pig lungs.
AB  - OBJECTIVE: Several works highlight the role of CsA in the prevention of IRI, but
      none focus on isolated lungs. Our objective was to evaluate the effects of CsA on
      IRI on ex vivo reperfused pig lungs. METHODS: Thirty-two pairs of pig lungs were
      collected and stored for 30 minutes at 4  degrees C. The study was performed in
      four groups. First, a control group and then three groups receiving different
      concentrations of CsA (1, 10, and 30 MUM) at two different times: once at the
      moment of lung procurement and another during the reperfusion procedure. The ex
      vivo lung preparation was set up using an extracorporeal perfusion circuit. Gas
      exchange parameters, pulmonary hemodynamics, and biological markers of lung
      injury were collected for the evaluation. RESULTS: CsA improved the PaO2 /FiO2
      ratio, but it also increased PAP, Pcap, and pulmonary vascular resistances with
      dose-dependent effects. Lungs treated with high doses of CsA displayed higher
      capillary-alveolar permeability to proteins, lower AFC capacities, and elevated
      concentrations of pro-inflammatory cytokines. CONCLUSIONS: These data suggest a
      possible deleterious imbalance between the beneficial cell properties of CsA in
      IRI and its hemodynamic effects on microvascularization.

PMID- 23952933
TI  - The Occupational Therapist's Role with Workers' Compensation and the ADA:
      Successful Work Accommodations and Strategies for Employer and Service Provider
      Partnership.

PMID- 23952934
TI  - Technology Solutions for ADA Compliance.

PMID- 23952935
TI  - Developing ADA Job Analyses: A Case Study.

PMID- 23952936
TI  - Shopping Mall Wheelchair Accessibility Checklist Based on the ADA Guidelines.

PMID- 23952937
TI  - Essential Functions: The Journey of an OT Student with Learning Disabilities.
AB  - This article is essentially the story of my journey, as a student with a learning
      disability, through the system. It is a very personal account designed to raise
      the awareness of those who deal with people during the recognition and evaluation
      stage of a learning disability. 

PMID- 23952938
TI  - Neuro-occupation: linking sensory deprivation and self-care in the ICU patient.
AB  - Neuro-occupation is an emerging concept in occupational therapy. The concept of
      neuro-occupation provides a basis to understand how the nervous system is
      intertwined with all aspects of occupational performance. This paper uses the
      framework of neuro-occupation to link a neurological system, the reticular
      activating system (RAS), to the performance of self-care by patients in an
      intensive care setting. This correlation is made because the RAS is responsible
      for organizing sensory information. Inappropriate amounts of stimulation effect
      the RAS and result in sensory deprivation or sensory overload, which negatively
      impacts occupational performance. Implications for occupational therapy practice
      are also addressed. 

PMID- 23952939
TI  - Spectroscopic study of the I2 formation from the photolysis of iodomethanes
      (CHI3, CH2I2, CH3I, and CH2ICl) at different wavelengths.
AB  - Emission spectra following the photolysis of iodomethanes (CHI3, CH2I2, CH3I, and
      CH2ICl) at 266 nm were recorded in a slow flow cell. In addition to emission from
      the electronically excited species including CH (A(2)Delta, B(2)Sigma(-), and
      C(2)Sigma(+)), C2 (d(3)Pig), and atomic iodine ((4)P(o)), a series of emission
      bands was observed in the 12,000-19,000 cm(-1) region. The dominant structure of
      these emission bands was verified as the I2 B(3)Pi(+)(0,u)-X(1)Sigma(+)g emission
      at the 532 nm excitation, and the observed I2 was formed from collisions between
      iodine atoms generated from the C-I bond dissociation in these iodomethanes. The
      I2 emission spectra following the photolysis of CH2I2 at different wavelengths
      were acquired, and the threshold energy for the first C-I bond cleavage was
      determined to be 208 +/- 1 kJ mol(-1). We also obtained the emission spectra of
      pure I2 at several visible excitation wavelengths for comparison with those from
      the photolysis of iodomethanes, and a least-squares global fit of the observed I2
      emission bands yields more accurate anharmonicity parameters for the vibrational
      structure in the I2 B-X transition.

PMID- 23952940
TI  - The effect of language barriers on dispatching EMS response.
AB  - OBJECTIVE: The objective of this study was to investigate the effect of language
      barriers during medical 9-1-1 calls, on the time to dispatch and level of medical
      aid (Basic or Advanced Life Support). METHODS: All 9-1-1 medical calls to two
      large call centers during one week for each of the months of August, October,
      December 2010 and February 2011, were reviewed for a notation of language barrier
      (LB). Non-language barrier calls were identified from the same time period such
      that there were an equal proportion of LB and non-LB calls by dispatch code and
      dispatcher. A total of 272 language barrier calls were identified. The computer
      assisted dispatch (CAD) reports for the LB and non-LB calls were abstracted by
      research staff using a standard form, including: Start time of call, time to
      dispatch of BLS, time to dispatch of ALS, dispatch code, interpretation service
      use, on-scene upgrade to ALS, and on-scene downgrade to BLS. 9-1-1 recordings
      were abstracted for LB calls only to obtain information about use of interpreter
      services. Difference between LB and English speakers in time to assignment of BLS
      and ALS was examined using linear mixed effects models with log time as the
      outcome; language barrier, call center and dispatch code as fixed effects and
      dispatcher as a random effect. RESULTS: The effect of language barrier on time to
      BLS assignment was, on average, 33% longer (p < 0.001) and time to ALS assignment
      43% longer (P = 0.008). A majority of the effect was due to the effect of
      interpreter use, which increased time to BLS by 82% and 125% for ALS, when
      compared to non-language barrier calls. Data from the 9-1-1 recordings showed an
      average of 49 seconds between connecting to the service operator and connecting
      to the language interpreter. Language barrier calls were more likely to be up-
      and down-graded, only statistically significantly so for on-scene downgrades.
      CONCLUSION: Language barriers increase time to dispatch and the accuracy of the
      level of aid dispatched during medical emergency calls. Decreasing the time to
      connecting to an actual interpreter when using an interpretation service could
      minimize existing delays.

PMID- 23952941
TI  - Injectable microsphere/hydrogel hybrid system containing heat shock protein as
      therapy in a murine myocardial infarction model.
AB  - Heat shock proteins, acting as molecular chaperones, protect heart muscle from
      ischemic injury and offer a potential approach to therapy. Here we describe
      preparation of an injectable form of heat shock protein 27, fused with a protein
      transduction domain (TAT-HSP27) and contained in a hybrid system of poly(d,l
      lactic-co-glycolic acid) microsphere and alginate hydrogel. By varying the porous
      structure of the microspheres, the release of TAT-HSP27 from the hybrid system
      was sustained for two weeks in vitro. The hybrid system containing TAT-HSP27 was
      intramyocardially injected into a murine myocardial infarction model, and its
      therapeutic effect was evaluated in vivo. The sustained delivery of TAT-HSP27
      substantially suppressed apoptosis in the infarcted site, and improved the
      ejection fraction, end-systolic volume and maximum pressure development in the
      heart. Local and sustained delivery of anti-apoptotic proteins such as HSP27
      using a hybrid system may present a promising approach to the treatment of
      ischemic diseases.

PMID- 23952942
TI  - Procainamide and lidocaine produce dissimilar changes in ventricular
      repolarization and arrhythmogenicity in guinea-pig.
AB  - Procainamide is class Ia Na(+) channel blocker that may prolong ventricular
      repolarization secondary to inhibition of IK r , the rapid component of the
      delayed rectifier K(+) current. In contrast to selective IN a blockers such as
      lidocaine, procainamide was shown to produce arrhythmogenic effects in the
      clinical setting. This study examined whether pro-arrhythmic responses to
      procainamide may be accounted for by drug-induced repolarization abnormalities
      including impaired electrical restitution kinetics, spatial gradients in action
      potential duration (APD), and activation-to-repolarization coupling. In perfused
      guinea-pig hearts, procainamide was found to prolong the QT interval on ECG and
      left ventricular (LV) epicardial monophasic APD, increased the maximum slope of
      electrical restitution, enhanced transepicardial APD variability, and eliminated
      the inverse correlation between the local APD and activation time values
      determined at distinct epicardial recording sites prior to drug infusion. In
      contrast, lidocaine had no effect on electrical restitution, the degree of
      transepicardial repolarization heterogeneities, and activation-to-repolarization
      coupling. Spontaneous episodes of monomorphic ventricular tachycardia were
      observed in 57% of procainamide-treated heart preparations. No arrhythmia was
      induced by lidocaine. In summary, this study suggests that abnormal changes in
      repolarization may contribute to pro-arrhythmic effects of procainamide. 

PMID- 23952943
TI  - Anisotropy of the thermal conductivity in GaAs/AlAs superlattices.
AB  - We combine the transient thermal grating and time-domain thermoreflectance
      techniques to characterize the anisotropic thermal conductivities of GaAs/AlAs
      superlattices from the same wafer. The transient grating technique is sensitive
      only to the in-plane thermal conductivity, while time-domain thermoreflectance is
      sensitive to the thermal conductivity in the cross-plane direction, making them a
      powerful combination to address the challenges associated with characterizing
      anisotropic heat conduction in thin films. We compare the experimental results
      from the GaAs/AlAs superlattices with first-principles calculations and previous
      measurements of Si/Ge SLs. The measured anisotropy is smaller than that of Si/Ge
      SLs, consistent with both the mass-mismatch picture of interface scattering and
      with the results of calculations from density-functional perturbation theory with
      interface mixing included. 

PMID- 23952944
TI  - Genomewide investigation into DNA elements and ABC transporters involved in
      imazalil resistance in Penicillium digitatum.
AB  - Penicillium digitatum, causing citrus green mold, is one of the most devastating
      pathogenic fungi for postharvest fruits. The disease control is becoming less
      efficient because of the dispersal of fungicide-resistant strains. However,
      genome-scale analyses of its resistance mechanism are scarce. In this work, we
      sequenced the whole genome of the R1 genotype strain Pd01-ZJU and investigated
      the genes and DNA elements highly associated with drug resistance. Variation in
      DNA elements related to drug resistance between P. digitatum strains was revealed
      in both copy number and chromosomal location, indicating that their recent and
      frequent translocation might have contributed to environmental adaptation. In
      addition, ABC transporter proteins in Pd01-ZJU were characterized, and the roles
      of typical subfamilies (ABCG, ABCC, and ABCB) in imazalil resistance were
      explored using real-time PCR. Seven ABC proteins, including the previously
      characterized PMR1 and PMR5, were induced by imazalil, which suggests a role in
      drug resistance. In summary, this work presents genome information of the R1
      genotype P. digitatum and systematically investigates DNA elements and ABC
      proteins associated with imazalil resistance for the first time, which would be
      indicative for studying resistant mechanisms in other pathogenic fungi. 

PMID- 23952945
TI  - [Efficacy of reperfusion therapy in syndrome of predominant right ventricular
      dysfunction associated with inferior myocardial infarction].
AB  - Aim of the study was choice of optimal tactics of treatment of patients with
      syndrome of predominant right ventricular (RV) dysfunction, associated with
      inferior myocardial infarction. We compared immediate and remote results of 3
      strategies of treatment of 100 patients admitted to N.V. Sklifosovsky Research
      Institute for Critical Care in 2003-2007: various methods of percutaneous
      coronary intervention (PCI), including delayed PCI in the acute period (n=48),
      thrombolytic therapy without subsequent PCI (n=20), conservative therapy without
      reperfusion therapy (n=32). Indications to delayed interventions were based on
      high risk of death due to RV infarction. It follows from the data obtained that
      optimal tactics of treatment of RV infarction is provision of availability of
      reperfusion therapy in the form of various types of PCI. Preferable are primary
      PCIs in the absence of which delayed PCIs acquire practical value. Thrombolytic
      therapy can be used as a component of combined reperfusion. Absence of signs of
      its efficacy on electrocardiogram during first 90 minutes serves as absolute
      indication for rescue PCI. Inaccessibility of the latter is a reason for
      provision of delayed interventions. Electrocardiographic signs of achieved
      pharmacological reperfusion do not exclude high probability of early recurrences
      of ischemia, expediency of application of PCI during the time preceding these
      recurrences. In the absence of PCI hospital and remote mortality have been very
      high. Optimization of accessibility of mechanical reperfusion including delayed
      allows to achieve efficacy of treatment of RV infarction, prevent development of
      complications and lethal outcomes. 

PMID- 23952946
TI  - [Multifocal atherosclerosis as a factor of unfavorable prognosis in patients with
      ST elevation myocardial infarction and type 2 diabetes mellitus].
AB  - Multifocal atherosclerosis (MFA) and diabetes mellitus (DM) determine less
      favorable course of acute vascular catastrophes. We analyzed dependence of one
      year prognosis of patients with myocardial infarction (MI) with and without DM on
      the presence of multifocal atherosclerosis. The analysis showed that number of
      cardiovascular complications increased with increase of degree of severity of
      atherosclerosis. Negative impact of DM on prognosis was more pronounced in
      patients with MFA. This effect rose with rise of atherosclerosis severity.
      Moreover in patients with MI stenoses of extracranial arteries including those
      less than 50% appeared to be markers of the disease severity and unfavorable
      prognosis especially at the background of DM. 

PMID- 23952947
TI  - [Effect of perindopril on the processes of subclinical inflammation in patients
      with arterial hypertension and type 2 diabetes mellitus].
AB  - We conducted comparative analysis of treatment 52 patients (7 men and 45 women
      aged 42-64 years, mean age 51.1 years) with I-II degree arterial hypertension
      (AH) and type 2 diabetes mellitus with the use of angiotensin converting enzyme
      inhibitor perindopril and with of other drugs. During 6 months effective control
      of AH was achieved on both treatments. We assessed changes in target organs at
      the background of 1 year therapy based on the use of perindopril or other
      antihypertensive preparations. Favorable changes of 24 hour indexes of arterial
      pressure accord in the group of perindopril treated patients compared with the
      group of patients treated with other antihypertensive drugs. Therapy with
      perindopril exerted organoprotective effect which manifested as lowering of
      microalbuminuria and augmentation of endothelium dependent vasodilation. We
      demonstrated ability of perindopril to affect proinflammatory status: to suppress
      factors of subclinical inflammation (interleukin-6 and C-reactive protein) and to
      elevate level of anti-inflammatory interleukin-10. 

PMID- 23952948
TI  - [Comparison of morphological features of carotid arteries atherosclerotic plaques
      with clinical-instrumental data in symptomatic and asymptomatic patients with
      severe carotid atherosclerosis].
AB  - A complex histomorphometric and clinical-instrumental analysis of atherosclerotic
      lesions of the carotid arteries obtained during carotid endarterectomies (CEE) of
      patients with hemodynamically significant stenoses was conducted. Two groups of
      patients were compared: symptomatic, which earlier underwent cerebral vascular
      accident (CVA) or transitory ischemic attacks (TIA), and asymptomatic ones with
      no complications of the disease. Statistical analysis of clinical and laboratory
      data showed no significant differences between two groups except for the level of
      lipoprotein(a) [Lp(a)] in the blood plasma, which was higher (p<0.05) in
      asymptomatic patients compared with symptomatic ones. Statistical analysis of
      carotid arteries ultrasound duplex scanning (USDS) in the preoperative period did
      not reveal significant differences in the degree of maximum vessels stenosis
      between the compared groups of patients. Surface defects of atherosclerotic
      plaques (ASP) were shown to be significantly more common (p<0.05) in the group of
      symptomatic patients compared with asymptomatic ones. According to histological
      analysis 88% of extracted ASP was unstable in symptomatic patients and 77% of ASP
      - in asymptomatic patients. This may indicate high risk of CVA/TIA in both groups
      of patients. Statistical evaluation of magnetic resonance tomography (MRT) and
      USDS techniques in comparison with abilities of the most reliable histological
      analysis showed that both non-invasive diagnostic methods are highly sensitive in
      detecting unstable ASP, though MRT showed higher level of specificity compared
      with USDS. 

PMID- 23952949
TI  - [Peculiarities of the course of arterial hypertension in patients with
      atherosclerotic stenoses of brachiocephalic arteries before and after surgery on
      carotid arteries].
AB  - Study aim was to investigate relationship between atherosclerosis of carotid
      arteries (CA) and the presence of arterial hypertension (AH) and possibilities of
      correction of AH after surgery. We examined 70 patients with episodes of
      elevation of arterial pressure (AP) scheduled for surgical interventions on
      brachiocephalic arteries (BCA) because of CA stenoses (n=50, group 1) or
      anomalies of BCA development (n=20, group 2). Before operation patients of group
      1 had higher mean AP than patients of group 2 (103.6+/-11.3 and 91.7+/-6.6 mm Hg,
      respectively, p=0.00007). This difference disappeared after surgery. In
      postoperative period in patients with CA stenoses levels of both systolic and
      diastolic AP decreased (from 145.1+/-14.7 to 135.6+/-12.3, p=0.02; and from
      83.3+/-10.2 78.1+/-9.7 mm Hg, =0.02, respectively). In group 2 no significant AP
      reduction was observed. Thus AP elevation in patients with involvement of BCA to
      a considerable degree is caused by CA stenosis. Surgical treatment of these
      patients facilitates lowering of AP. 

PMID- 23952950
TI  - [Dynamics of parameters of systemic inflammation and hemocoagulation in early
      postoperative period in patients with heart valve prostheses].
AB  - In 42 patients with rheumatic heart defects before implantation of mechanical
      valves and on days 5 and 20 after surgery we measured parameters of hemostasis,
      levels of proinflammatory cytokines (interleukin 6 [IL-6], tumor necrosis factor-
      [TNF-] and C-reactive protein [CRP]) as well as activity of enzymes (alanine
      aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatine
      phosphokinase and its MB fraction). On day 5 after surgery we revealed
      substantial elevation of IL-6, TNF-, and CRP levels, increase of activity of the
      studied enzymes, contents of fibrinogen and soluble fibrin monomer complexes
      (SFMC), and to the contrary lowering of antithrombin III level and decrease of
      number of platelets. On day 20 IL-6 and TNF- levels remained significantly
      elevated compared to preoperative values. Concentrations of enzymes and
      parameters of hemostasis returned to baseline values while content of SFMC
      remained significantly decreased. In early postoperative period levels of IL-6
      and TNF- significantly correlated with that of SFMC and platelet count what
      reflected interrelation ship of processes of inflammation and coagulation.
      Severity of systemic inflammatory reaction in patients with implanted prosthetic
      valves influenced optimal doses of warfarin. 

PMID- 23952951
TI  - [Diurnal blood pressure profiles in night shift workers with incipient changes of
      blood pressure level].
AB  - Aim. To study diurnal blood pressure profiles (DBPP) during work in different
      time of the day including nocturnal hours in persons with initial stages of blood
      pressure (BP) increase or decrease. Material and methods. The study cohort
      consisted of 995 locomotive drivers (46682 BP measurements) divided into groups
      with normal BP, higher normal BP, 1st stage arterial hypertension, and
      hypotension. DBPP was analyzed on the basis of the averaged curve for each group.
      Results. The averaged systolic DBPP in the normotonic group was of non-dipper
      type, while diastolic one was on the border between non-dipper and night-peaker.
      Patients with elevated BP and trend to BP elevation (beginning with higher normal
      BP) had reduced nocturnal BP lowering, particularly of diastolic BP. Its diurnal
      profile was clearly of night-peaker type. The main feature of DBPP in patients
      with hypotension was absence of evening BP rise characteristic for persons with
      normal BP and hypertension. 

PMID- 23952952
TI  - [Primary and secondary prevention of cardio-vascular diseases: main directions of
      a national multicenter study in Tajikistan].
AB  - Data on goals and tasks of the prospective national study of detection of risk
      factors as well as of realization of primary and secondary prevention of ischemic
      heart disease in the Republic Tajikistan are presented in this paper. According
      to protocol the study has two stages. Stage 1 is a single step (cross sectional)
      clinico-epidemiological study with 1000 participants with arterial hypertension
      and ischemic heart disease (n=1000) from 4 cities - regional republican centers.
      Socio-demographic parameters and main risk factors of development of these
      diseases in working age men and women will be investigated at this stage.
      Efficacy of complex preventive, medical and surgical interventions will be
      assessed at stage 2 in a prospective comparative randomized study with duration
      of 3 years. Final results will be available in 2016. 

PMID- 23952953
TI  - [Protective action of ethylglutathione at hypoxia-reoxygenation of the heart:
      role of glucose].
AB  - Glutathione is the main redox buffer in cardiomyocytes. The action of
      ethylglutathione possessing antioxidant properties on functional disorders evoked
      by 30-minute hypoxia of the isolated rat heart with subsequent reoxygenation has
      been studied. In control experiments, the presence of glucose (11 mM) in hypoxic
      perfusate was associated with lesser hypoxic contracture of the myocardium but
      also with the development of arrhythmias in all experiments, including
      ventricular tachycardias and fibrillation that may be due to arisen myocardial
      heterogeneity. After reoxygenation, a half of hearts in this group demonstrated
      inability to reproduce high rate of stimulation. These alterations were almost
      completely prevented when ethylglutathione (0.2 mM) was added into hypoxic
      perfusate. Its presence in the solution also facilitated 1.5-fold improvement of
      cardiac function recovery after reoxygenation. The results suggest that the
      protective action of ethylglutathione may be due to a reduced oxidative
      modification of ionic transport proteins. At non-glucose hypoxic perfusion,
      myocardial contracture was higher but abovementioned functional disorders did not
      arise, and ethylglutathione addition was inefficient. 

PMID- 23952954
TI  - [An association of the 825 polymorphism of the g protein 3 subunit with obesity
      in Kyrgyz population].
AB  - GOAL: To study an association of G protein (GP) 3 subunit 825 polymorphism with
      obesity in native Kyrgyzes. MATERIAL AND METHODS: 210 persons: 89 patients
      (female - 35, male - 54) with obesity (body mass index [BMI] more or equal 30
      kg/m2) and 121 apparently healthy controls (38 female, 83 male) with normal BMI.
      Arterial blood pressure, anthropometric measurement and laboratory tests for
      blood glucose and lipid parameters were performed in all examined persons. DNA
      was extracted from blood cells and GP3 subunit 825 polymorphism was determined by
      PCR method. RESULTS: groups with TT and CT genotypes were combined together
      because of the rare frequency of TT genotype. Prevalence of + genotypes in group
      with obesity (0.72) was significantly higher than in controls - 0.52 (odds ratio
      2.55, 95% confidence interval [CI] 1.31-4.23; =0.004). Arterial hypertension (45
      vs. 31.3%; =0,049) and obesity (51.2 vs. 30%; p<0.01) occurred more often in +
      genotypes carriers compared with CC homozygotes. A logistic regression model for
      obesity showed significant effect of 825T allele (relative risk [RR] 2.89, 95% CI
      1.25-6.7; =0.013) and irregular intake of vegetables (RR 3.47, 95% CI 1.52-7.94;
      =0.003) as predictors of obesity development independent of age, sex and physical
      activity level. In the regression model for arterial hypertension the 825T allele
      lost its significance after adjustment for obesity. CONCLUSION: GP3 subunit 825
      allele in native Kyrgyzes is associated with obesity.

PMID- 23952955
TI  - [Myocardial revascularization before abdominal aortic surgery in patients with
      ischemic heart disease].
AB  - We retrospectively analyzed 2 cohorts of patients treated in two clinics
      implementing different strategies of preoperative examination and lowering of
      perioperative cardiac risk. Patients in clinic 1 (group I, n=86, mean age 59.4+/
      7.7 years) were subjected to coronary angiography (CAG) and if indicated - to
      preventive myocardial revascularization. In patients of clinic 2 (group II, n=95,
      mean age 54.3+/-6.5 years) only medical therapy was used. In group I CAG was
      performed in 90%, and myocardial revascularization - in 28% of patients. Total
      number of complications and hospital mortality were significantly higher in group
      II compared with group I (20 vs. 8%, p=0.023; 10.5 vs. 2.3%, =0.026). Myocardial
      infarction was the cause of 6 deaths (6.3%) in group II, while in group I there
      were no cardiac complications. Thus compared to control group strategy with
      routine CAG and preventive myocardial revascularization before abdominal aortic
      surgery was associated with less perioperative complications, myocardial
      infarctions, and lower mortality. 

PMID- 23952956
TI  - [The rational approach to the estimation of the myocardial infarction size].
AB  - The paper contains review of published data on various methods of quantitative
      assessment of myocardial infarction (MI) with demonstration of their advantages
      and drawbacks. Comparative analysis of applicability of existing biochemical
      markers of necrosis for measurement of the volume of myocardial damage is also
      presented. Troponin I level measured in 72 hours after onset of chest pain
      appears to be the most reliable predictor of MI size but its use is justified
      only in patients with restored perfusion. Troponin T level measured in 72 hours
      after onset of acute coronary syndrome also correlates closely with MI size but
      does not depend on the character of reperfusion. Estimation of MI size based on
      blood concentration of troponins is more precise than methods based on levels of
      creatine phosphokinase and its MB fraction. 

PMID- 23952957
TI  - [The place of lercanidipine in the treatment of cardiovascular diseases].
AB  - The data are presented on using the first, second and third generation calcium
      antagonists in cardio-vascular pathology patients. The accent has been made on
      the improved pharmacokinetic profile of the third generation calcium antagonists
      where modern preparation lerkanidipin belongs to. It is shown that lerkanidipine
      has expressed antihypertensive effect with no significant impact on the cardiac
      contraction frequency and its metabolic neutrality enables using the said
      preparation with diabetes mellitus and other metabolic disorders patients.
      Besides, an improved pharmacokinetic lerkanidine profile leads to
      organoprotective and antiaterogeneous effect. Significantly fewer side reactions
      as connected with activised simpatico-adrenal system, and peripheral edemas are
      observed as compared against other representatives of the said preparations
      category. 

PMID- 23952958
TI  - [Diabetes mellitus as hypercoagulate state: ways of preventing].

PMID- 23952959
TI  - [Endovascular closure of the left atrial appendage in patients with atrial
      fibrillation: review of modern data and own experience of application].
AB  - Atrial fibrillation (AF) is the most often disturbance of cardiac rhythm met in
      clinical practice. Long term therapy with anticoagulants is used for prevention
      of thrombi formation in left atrial appendage and consequent thromboembolism.
      However some patients have contraindications to this therapy. This article
      contains consideration of various alternative methods of prevention of
      thromboembolic complications in particular those 2 which are most widely used at
      present - percutaneous transcatheter isolation of left atrial appendage with
      Amplatzer Cardiac Plug () or Watchman Device. We present also data on own
      experience of the use of the ACP device. 

PMID- 23952960
TI  - [Myocardial infarction secondary to blunt chest trauma in a man of 25 years].
AB  - This paper describes the clinical case - anterior myocardial infarction after
      blunt chest trauma in a 25-year-old man. 

PMID- 23952961
TI  - Population-based survey of refractive error among school-aged children in rural
      northern China: the Heilongjiang eye study.
AB  - BACKGROUND: The prevalence of refractive error in the north of China is unknown.
      The study aimed to estimate the prevalence and associated factors of refractive
      error in school-aged children in a rural area of northern China. DESIGN: Cross
      sectional study. PARTICIPANTS OR SAMPLES: The cluster random sampling method was
      used to select the sample. METHODS: A total of 1700 subjects of 5 to 18 years of
      age were examined. All participants underwent ophthalmic evaluation. Refraction
      was performed under cycloplegia. Association of refractive errors with age, sex,
      and education was analysed. MAIN OUTCOME MEASURES: The main outcome measure was
      prevalence rates of refractive error among school-aged children. RESULTS: Of the
      1700 responders, 1675 were eligible. The prevalence of uncorrected, presenting,
      and best-corrected visual acuity of 20/40 or worse in the better eye was 6.3%,
      3.0% and 1.2%, respectively. The prevalence of myopia was 5.0% (84/1675, 95% CI,
      4.8%-5.4%) and of hyperopia was 1.6% (27/1675, 95% CI, 1.0%-2.2%). Astigmatism
      was evident in 2.0% of the subjects. Myopia increased with increasing age,
      whereas hyperopia and astigmatism were associated with younger age. Myopia,
      hyperopia and astigmatism were more common in females. We also found that
      prevalence of refractive error were associated with education. Myopia and
      astigmatism were more common in those with higher degrees of education.
      CONCLUSION: This report has provided details of the refractive status in a rural
      school-aged population. Although the prevalence of refractive errors is lower in
      the population, the unmet need for spectacle correction remains a significant
      challenge for refractive eye-care services.

PMID- 23952962
TI  - Efficacy and safety of probiotics in the treatment of Candida-associated
      stomatitis.
AB  - This study aimed at evaluating the short-term efficacy and safety of probiotics
      as an aid in the treatment of Candida-associated stomatitis in a randomised
      controlled trial. A total of 65 patients were randomly assigned to receive oral
      local antifungal agents alone (gargle 2% sodium bicarbonate solution for 30 s,
      wait 10 min and then apply 2% nystatin paste) or these agents plus local
      probiotics (the mixture of Bifidobacterium longum, Lactobacillus bulgaricus and
      Streptococcus thermophilus) three times per day for 4 weeks. Parameters related
      to hyperaemia, visual analogue scale scores, culture of resting saliva and a
      lingual dorsum swab and adverse reactions were assessed or recorded in the
      beginning, middle and end of treatment. Although the baseline characteristics of
      the participants were similar, both groups showed a significant reduction in pain
      level and hyperaemia on the tongue mucosa (P = 0.000) after 4-week application.
      However, despite the reduction in hyperaemia in the probiotic group, these
      improvements did not display statistically significant differences. The detection
      rate of Candida spp. was 100% before treatment and 8.21% in the experimental
      group and 34.6% in the control group after treatment. The detection rate of
      Candida spp. decreased (P = 0.000) in both groups and was significantly lower in
      the probiotic group than the control group (P = 0.038). Other analysed micro
      organisms, including the decreased detection rate for Lactobacillus spp. (P =
      0.049) and the increased detection rate for Staphylococcus epidermidis (P =
      0.019), did not display consistent change trends in the probiotics group.
      Compared with conventional antifungal therapies for oral candidiasis, the
      inclusion of locally administered probiotics helped improve certain clinical
      conditions and reduced the prevalence of Candida spp., although the impact of
      probiotics on oral bacterial species remains to be further studied. 

PMID- 23952963
TI  - Crosstalk between dopamine D2 receptors and cannabinoid CB1 receptors regulates
      CNR1 promoter activity via ERK1/2 signaling.
AB  - Previously, we found that chronic methamphetamine treatment altered cannabinoid
      type 1 receptor (CB1R)-dependent cAMP/PKA/dopamine and cAMP-regulated
      phosphoprotein of Mr 32,000 (DARPP-32)/T34/PP2B signaling and decreased levels of
      CB1R protein and mRNA in the nucleus accumbens. These findings suggested the
      existence of signaling interplay between mesolimbic dopamine and CB1R. In this
      study, we further investigate interactions between CB1R and dopamine D2 receptor
      (D2R) signaling. Activation of either CB1R or D2R increased extracellular signal
      regulated kinases 1 and 2 (ERK1/2) phosphorylation, while co-stimulation of CB1R
      and D2 R evoked an additive effect on the phospho-ERK1/2 signal. This effect was
      mediated through a pertussis toxin-sensitive Galphai/o pathway in primary
      striatal cells. Furthermore, the mRNA level of CB1R was increased via dopamine D2
      receptor short form (D(2S)R) by treatment with D2R agonist quinpirole in
      D(2S)R/C6 glioma cells. This effect could be suppressed by co-treatment with the
      ERK1/2 inhibitor U0126. To test if D(2S)R could transcriptionally regulate CB1R,
      the 5'-untranslated region (5'-UTR) of the cannabinoid receptor 1 (CNR1) gene was
      sequenced from rat brain. Results showed that the CNR1 gene includes two exons,
      which contain 375 bp of 5'-UTR and are separated by a 17-kb intron. A luciferase
      reporter assay showed that the maximal D(2S)R-responsive promoter activity is
      located in the -1 to -222 region of CNR1 promoter. Overall, we demonstrate
      previously unidentified crosstalk between D2R and CB1R via ERK1/2 signaling that
      enhances the expression of CB1R by modulating its promoter activity.

PMID- 23952964
TI  - Surface-coating-dependent dissolution, aggregation, and reactive oxygen species
      (ROS) generation of silver nanoparticles under different irradiation conditions.
AB  - Dissolution, aggregation, and reactive oxygen species (ROS) generation are three
      major processes that silver nanoparticles (AgNPs) undergo in aqueous
      environments. In this study, the effects of AgNP surface coatings on these three
      processes were systematically evaluated under three irradiation conditions (UV
      365, UV-254, and xenon lamp) to advance knowledge on the environmental fate and
      photochemical kinetics of AgNPs. The AgNPs used were (a) bare-AgNPs, (b)
      electrostatically stabilized citrate-AgNPs, and (c) sterically stabilized
      polyvinylpyrrolidone-AgNPs (PVP-AgNPs), and the light exposures greatly promoted
      the three processes. Both the 5-h released Ag(+) concentrations and the 2.5-h
      aggregation rate followed the order UV-365 > xenon lamp > UV-254 for all three
      types of AgNPs. For all irradiation conditions, the 5-h released Ag(+)
      concentration was highest for bare-AgNPs, followed by PVP-AgNPs and citrate
      AgNPs; the 2.5-h aggregation rate was highest for bare-AgNPs, followed by citrate
      AgNPs and PVP-AgNPs, which indicated that surface coating significantly
      determines the process kinetics of AgNPs. Under UV-365 irradiation, the bare
      AgNPs generated superoxide and hydroxyl radicals, but the citrate-AgNPs yielded
      only superoxide radical, and the PVP-AgNPs did not generate any ROS. This study
      highlights the different fates and kinetic behaviors of AgNPs during
      photochemical interactions, providing important insight into the environmental
      implications of AgNP release. 

PMID- 23952965
TI  - Metabolomic investigation of pathogenesis of myxosporean emaciation disease of
      tiger puffer fish Takifugu rubripes.
AB  - Serum biochemical analysis was undertaken to study the pathophysiological details
      of emaciation disease of the tiger puffer fish Takifugu rubripes (Temminck and
      Schlegel). Serum parameters were measured by biochemical analysis using automated
      dry chemistry and gas chromatography/mass spectrometry (GC/MS). Serum
      concentrations of albumin, amylase, calcium, creatinine, glucose and total
      protein were significantly lower in the emaciated fish when compared with those
      of normal fish. Regression analyses found close correlation between
      concentrations of total protein, albumin, amylase, glucose and progress of the
      disease. In contrast, serum alanine aminotransferase increased significantly in
      emaciated fish indicating liver function disorder. Further, GC/MS metabolic
      profiling of the puffer serum showed that the profile of the emaciated fish was
      distinct to that of non-infected control. The serum content of amino acids
      including glycine, 5-oxo-proline and proline, and ascorbic acid, fumaric acid and
      glycerol increased significantly in serum in moderately emaciated fish. The serum
      glucose, linolenic acid and tyrosine level decreased significantly in the late
      phase of the disease. Our results clearly show that prolonged intestinal damage
      caused by myxosporean infection impairs absorption of nutrients, resulting in
      extreme emaciation. 

PMID- 23952966
TI  - The RNA polymerase II carboxy-terminal domain (CTD) code.

PMID- 23952967
TI  - Renal transplantation in indigenous Australians of the Northern Territory:
      closing the gap.
AB  - Chronic kidney disease causes high morbidity and mortality among Indigenous
      Australians of the Northern Territory (NT). Studies have shown chronic kidney
      disease rates of 4-10 times higher in indigenous than non-indigenous Australians
      and prevalent dialysis rates of 700-1200 per million population. For most
      patients with end-stage renal failure, renal transplantation provides the optimal
      treatment for people with end-stage renal disease. It reduces morbidity and
      mortality, and improves survival and quality of life. Graft and patient survival
      rates of over 80% at 5 years depending on the donor source (deceased vs living
      donor) are expected worldwide. However, this is not the case in Indigenous
      Australians of the NT where graft and patient survival are both around 50% at 5
      years suggesting death with functioning graft as the most common cause of graft
      loss. It would provide the best treatment option for indigenous people most of
      who live in remote (18%) and very remote communities (63%). Many have to relocate
      from their communities to urban or regional centres for dialysis. Available
      options to avoid relocation include peritoneal dialysis, home haemodialysis and
      community health centre dialysis, but the acceptance rates for these are low,
      hence renal transplantation would provide the best option. There is evidence of
      identified barriers to renal transplantation for indigenous people of the NT.
      This review explores published data on why rates of renal transplantation in
      indigenous people of the NT are low and the reasons for poor outcomes
      highlighting possible areas of improvement. 

PMID- 23952968
TI  - Breastfeeding practices and child growth outcomes in Haiti: an analysis of data
      from Demographic and Health Surveys.
AB  - Haiti's national nutrition policy prioritises breastfeeding, but limited data are
      available to inform strategy. We examined national trends in early initiation of
      breastfeeding (ErIBF) and exclusive breastfeeding (EBF) over a 10-year period
      using data from three Haitian Demographic and Health Surveys (1994-1995, 2000 and
      2005-2006). We used multivariate regression methods to identify determinants of
      ErIBF and EBF in the 2005-2006 data set and to examine relationships to growth.
      There was no change in ErIBF across surveys [1994-1995: 36.6%, 95% confidence
      interval (CI) 29.9-43.9; 2000: 49.4%, 95% CI 44.1-54.8; 2005-2006: 43.8%, 95% CI
      40.5-47.1]. EBF among 0-5-month-olds increased sharply (1994-18995: 1.1%, 95% CI
      0.4-3.2; 2000: 22.4%, 95% CI 16.5-29.5; 2005-2006: 41.2%, 95% CI 35.4-47.2). The
      proportion of breastfeeding children 0-5 months who received soft, solid or semi
      solid foods decreased (1994-1995: 68.5%, 95% CI 57.3-77.9; 2000: 46.3%, 95% CI
      39.3-53.4; 2005-2006: 30.9%, 95% CI 25.9-36.5). Child age at time of survey [odds
      ratio (OR) 1.73; P = 0.027], lower maternal education (OR = 2.14, P = 0.004) and
      residence in the Artibonite Department (OR 0.31; P = 0.001) were associated with
      ErIBF among children 0-23 months. Age group and department were significant
      predictors of EBF among children 0-5 months. ErIBF was associated with higher
      weight-for-age z-scores [effect size (ES) 0.22; P = 0.033] and height-for-age z
      scores (ES 0.20; P = 0.044). There was no statistically significant relationship
      between EBF and growth. The 10-year ErIBF and EBF trends in Haiti echo global and
      regional trends. ErIBF and EBF are related practices but with different
      determinants in the Haitian context. These differences have implications for
      intervention delivery. 

PMID- 23952969
TI  - Tailoring directional scattering through magnetic and electric resonances in
      subwavelength silicon nanodisks.
AB  - Interference of optically induced electric and magnetic modes in high-index all
      dielectric nanoparticles offers unique opportunities for tailoring directional
      scattering and engineering the flow of light. In this article we demonstrate
      theoretically and experimentally that the interference of electric and magnetic
      optically induced modes in individual subwavelength silicon nanodisks can lead to
      the suppression of resonant backscattering and to enhanced resonant forward
      scattering of light. To this end we spectrally tune the nanodisk's fundamental
      electric and magnetic resonances with respect to each other by a variation of the
      nanodisk aspect ratio. This ability to tune two modes of different character
      within the same nanoparticle provides direct control over their interference,
      and, in consequence, allows for engineering the particle's resonant and off
      resonant scattering patterns. Most importantly, measured and numerically
      calculated transmittance spectra reveal that backward scattering can be
      suppressed and forward scattering can be enhanced at resonance for the particular
      case of overlapping electric and magnetic resonances. Our experimental results
      are in good agreement with calculations based on the discrete dipole approach as
      well as finite-integral frequency-domain simulations. Furthermore, we show useful
      applications of silicon nanodisks with tailored resonances as optical
      nanoantennas with strong unidirectional emission from a dipole source. 

PMID- 23952970
TI  - The effectiveness of different concentrations of chlorhexidine for prevention of
      ventilator-associated pneumonia: a meta-analysis.
AB  - AIMS AND OBJECTIVES: To evaluate the effectiveness of chlorhexidine for the
      prevention of ventilator-associated pneumonia and explore the preferred
      concentration of chlorhexidine. BACKGROUND: The implementation of effective oral
      care measures could reduce the incidence of ventilator-associated pneumonia, but
      among several randomised controlled trials, whether using chlorhexidine is
      effective and which concentration is more appropriate remain controversial.
      DESIGN: A meta-analysis was conducted. METHODS: We searched the Cochrane Library,
      PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, China
      Biology Medicine disc and Chinese National Knowledge Infrastructure to collect
      randomised controlled trials of mechanically ventilated adult patients receiving
      oral care with chlorhexidine to prevent ventilator-associated pneumonia. The
      quality of randomised controlled trials was critically appraised, data were
      extracted by two reviewers independently, and disagreement was resolved by
      consensus. Meta-analyses were conducted for the eligible randomised controlled
      trials by revman 5.1. Relative risks and 95% CIs were calculated with the Mantel
      Haenszel model, and heterogeneity was assessed with the I(2) test. RESULTS:
      Eighteen randomised controlled trials were included and a meta-analysis was used.
      All studies indicated chlorhexidine could significantly prevent and reduce the
      incidence of ventilator-associated pneumonia [RR = 0.59, 95% CI (0.50-0.69), p <
      0.00001]. Nine studies showed 0.12% chlorhexidine had a significant effect [RR =
      0.53, 95% CI (0.43-0.67), p < 0.00001]. Three studies proved the effect of the 2%
      chlorhexidine on the prevention of ventilator-associated pneumonia [RR = 0.55,
      95% CI (0.37-0.81), p = 0.002]. CONCLUSION: Chlorhexidine can prevent and reduce
      the incidence of ventilator-associated pneumonia. Chlorhexidine of 0.12% has the
      best effect on the prevention of ventilator-associated pneumonia according to the
      meta-analysis, cost analysis, adverse reactions and drug resistance analysis.
      RELEVANCE TO CLINICAL PRACTICE: Ventilator-associated pneumonia remains a leading
      cause of morbidity and mortality in intensive care unit, and implementing
      effective oral care can reduce the incidence of ventilator-associated pneumonia.
      Chlorhexidine of 0.12% is recommended in our study.

PMID- 23952971
TI  - Core-shell tin oxide, indium oxide, and indium tin oxide nanoparticles on silicon
      with tunable dispersion: electrochemical and structural characteristics as a
      hybrid Li-ion battery anode.
AB  - Tin oxide (SnO2) is considered a very promising material as a high capacity Li
      ion battery anode. Its adoption depends on a solid understanding of factors that
      affect electrochemical behavior and performance such as size and composition. We
      demonstrate here, that defined dispersions and structures can improve our
      understanding of Li-ion battery anode material architecture on alloying and co
      intercalation processes of Lithium with Sn from SnO2 on Si. Two different types
      of well-defined hierarchical Sn@SnO2 core-shell nanoparticle (NP) dispersions
      were prepared by molecular beam epitaxy (MBE) on silicon, composed of either
      amorphous or polycrystalline SnO2 shells. In2O3 and Sn doped In2O3 (ITO) NP
      dispersions are also demonstrated from MBE NP growth. Lithium alloying with the
      reduced form of the NPs and co-insertion into the silicon substrate showed
      reversible charge storage. Through correlation of electrochemical and structural
      characteristics of the anodes, we detail the link between the composition, areal
      and volumetric densities, and the effect of electrochemical alloying of Lithium
      with Sn@SnO2 and related NPs on their structure and, importantly, their
      dispersion on the electrode. The dispersion also dictates the degree of co
      insertion into the Si current collector, which can act as a buffer. The
      compositional and structural engineering of SnO2 and related materials using
      highly defined MBE growth as model system allows a detailed examination of the
      influence of material dispersion or nanoarchitecture on the electrochemical
      performance of active electrodes and materials. 

PMID- 23952972
TI  - Benefits of combined modality treatment of Merkel cell carcinoma of the head and
      neck: single institution experience.
AB  - BACKGROUND: There is ongoing debate surrounding the roles of surgery and adjuvant
      radiotherapy in the management of primary and recurrent Merkel cell carcinoma of
      the head and neck. This study assessed the influence of local excision, margin
      status, adjuvant radiotherapy and chemotherapy on locoregional recurrence and
      survival. METHOD: A retrospective review of 54 consecutive cases of head and neck
      Merkel cell carcinoma at a single institution. RESULTS: Median disease-specific
      survival time was 120 months. Forty-four per cent of patients developed
      locoregional recurrence. Combined treatment with surgery and locoregional
      radiotherapy improved diseasespecific survival. Radiotherapy was associated with
      longer time to recurrence and regional recurrence. Irradiation of the regional
      nodes improved regional control, irrespective of clinical status. Margin-negative
      excision was not associated with improved local control. Combined modality
      treatment of recurrent disease resulted in a four-fold improvement of local
      control, but small numbers prevented this trend from reaching statistical
      significance. CONCLUSION: Surgical excision of the primary disease and clinically
      involved regional nodes, plus adjuvant radiotherapy to the surgical bed and
      regional nodes are recommended for all patients with Merkel cell carcinoma of the
      head and neck, irrespective of clinical status. Recurrent disease should be
      aggressively treated with combined modality treatment.

PMID- 23952973
TI  - Evolutionary and Ecological Dynamics of Transboundary Disease Caused by H5N1
      Virus in Southeast Asia.
AB  - Southeast Asia has been the breeding ground for many emerging diseases in the
      past decade, and it is in this region that new genetic variants of HPAI H5N1
      viruses have been emerging. Cross-border movement of animals accelerates the
      spread of H5N1, and the changing environmental conditions also exert strong
      selective pressure on the viruses. The transboundary zoonotic diseases caused by
      H5N1 pose a serious and continual threat to global economy and public health.
      Here, we divided the H5N1 viruses isolated in Southeast Asia during 2003-2009
      into four groups according to their phylogenetic relationships among HA gene
      sequences. Molecular evolution analysis suggests populations in expansion rather
      than a positive selection for group 2 and group 3, yet group 4 is under strong
      positive selection. Site 193 was found to be a potential glycosylation site and
      located in receptor-binding domain. Note that site 193 tends to appear in avian
      isolates instead of human strains. Population dynamics analysis reveals that the
      effective population size of infections in Southeast Asia has undergone three
      obvious increases, and the results are consistent with the epidemiological
      analysis. Ecological and phylogeographical analyses show that agro-ecological
      environments, migratory birds, domestic waterfowl, especially free-ranging ducks,
      are crucial in the occurrence, maintenance and spread of H5N1 virus. The
      epidemiological links between Indonesia and Suphanburi observed suggest that
      viruses in Indonesia were originated from multiple introductions. 

PMID- 23952974
TI  - Trigeminal neuralgia.

PMID- 23952976
TI  - Economic evaluation of cell salvage in pediatric surgery.
AB  - BACKGROUND: Red blood cells are a scarce resource with demand outstripping
      supply. Use of intraoperative red cell salvage (CS) - the process of collecting
      shed blood during surgery and reinfusing it to patients - is often used as an
      effective blood conservation strategy. However, little is known about the
      economic impact of CS during pediatric surgery. METHODS: A decision tree model
      was used to estimate the transfusion-related costs per patient (2010 USD) from a
      healthcare system perspective of four transfusion strategies among children
      undergoing elective orthopedic or cardiac surgery: (i) CS followed by allogeneic
      transfusion, (ii) CS followed by autologous transfusion, (iii) allogeneic
      transfusion alone, and (iv) autologous transfusion alone. RESULTS: Cell salvage
      and allogeneic transfusion was the least expensive strategy (USD 883.3) followed
      by CS and autologous blood transfusion (USD 1,269.7), allogeneic transfusion
      alone (USD 1,443.0), and autologous transfusion alone (USD 1,824.7). Savings
      associated with CS use persisted in separate analyses of orthopedic and cardiac
      surgery, as well as in one-way and probabilistic sensitivity analyses.
      CONCLUSIONS: Use of CS, particularly along with allogeneic blood transfusion,
      appears cost-saving and cost-effective in pediatric surgery.

PMID- 23952975
TI  - Ixodes ricinus abundance and its infection with the tick-borne pathogens in urban
      and suburban areas of Eastern Slovakia.
AB  - BACKGROUND: Raising abundance of ticks and tick-borne diseases in Europe is the
      result of multiple factors including climate changes and human activities.
      Herein, we investigated the presence and seasonal activity of Ixodes ricinus
      ticks from 10 urban and suburban sites in two different geographical areas of
      southeastern and northeastern Slovakia during 2008-2010. Our aim was to study the
      abundance of ticks in correlation with the environmental factors and their
      infection with Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum and
      Neoehrlichia mikurensis. METHODS: Questing I. ricinus ticks were collected from
      ten urban and suburban sites in Eastern Slovakia. A total of 670 ticks were
      further analysed for the presence of B. burgdorferi s.l., A. phagocytophilum and
      N. mikurensis by molecular methods. Tick site and environmental relations were
      analysed using General Linear Models (LM). The differences between the number of
      Lyme borreliosis cases between the Kosice and Bardejov regions during a ten-year
      period were tested by Wilcoxon matched pairs test. RESULTS: In total, 2921 (1913
      nymphs, 1008 adults) I. ricinus ticks were collected from 10 study sites during
      the main questing season. Tick activity and relative abundance differed between
      locations and months. Temperature and humidity were the main factors affecting
      the tick abundance and questing activity. Out of 670 examined ticks, 10.15% were
      infected with spirochetes from B. burgdorferi s.l. complex (represented by B.
      afzelii, B. garinii, B.valaisiana and B. burgdorferi s.s.), 2.69% with the A.
      phagocytophilum and 2.39% with N. mikurensis. The number of Lyme borreliosis
      cases per 100,000 inhabitants in the Bardejov region was significantly higher
      than in the Kosice region. CONCLUSIONS: Our data indicate that the risk of
      infection with tick-borne pathogens in Eastern Slovakia is common since 15.2% of
      ticks were infected at least with one of the tested microorganisms. Even though
      the abundance of ticks was affected by the microclimatic conditions and the
      prevalence of pathogens differed between the habitats, the infection risk for
      humans is also affected by human activities leading to an increased contact with
      infected ticks.

PMID- 23952977
TI  - The use of predefined diet quality scores in the context of CVD risk during
      urbanization in the South African Prospective Urban and Rural Epidemiological
      (PURE) study.
AB  - OBJECTIVE: Urbanization is generally associated with increased CVD risk and
      accompanying dietary changes. Little is known regarding the association between
      increased CVD risk and dietary changes using approaches such as diet quality. The
      relevance of predefined diet quality scores (DQS) in non-Western developing
      countries has not yet been established. DESIGN: The association between dietary
      intakes and CVD risk factors was investigated using two DQS, adapted to the black
      South African diet. Dietary intake data were collected using a quantitative FFQ.
      CVD risk was determined by analysing known CVD risk factors. SETTING: Urban and
      rural areas in North West Province, South Africa. SUBJECTS: Apparently healthy
      volunteers from the South African Prospective Urban and Rural Epidemiological
      (PURE) study population (n 1710). RESULTS: CVD risk factors were significantly
      increased in the urban participants, especially women. Urban men and women had
      significantly higher intakes of both macro- and micronutrients with macronutrient
      intakes well within the recommended CVD guidelines. While micronutrient intakes
      were generally higher in the urban groups than in the rural groups, intakes of
      selected micronutrients were low in both groups. Both DQS indicated improved diet
      quality in the urban groups and good agreement was shown between the scores,
      although they seemed to measure different aspects of diet quality. CONCLUSIONS:
      The apparent paradox between improved diet quality and increased CVD risk in the
      urban groups can be explained when interpreting the cut-offs used in the scores
      against the absolute intakes of individual nutrients. Predefined DQS as well as
      current guidelines for CVD prevention should be interpreted with caution in non
      Western developing countries.

PMID- 23952979
TI  - [Should physicians be called in for critically ill or seriously injured people?].

PMID- 23952978
TI  - [It is alright to use a medical writer in medical research].

PMID- 23952980
TI  - [Medical writers in medical research].
AB  - Larger research units often comprise persons of several professions in order to
      secure a high level of efficiency and quality in the different tasks. In Denmark,
      employees with special competencies within the field of writing and publication
      are rarely used in research units. The purpose of this study was to present the
      advantages and challenges associated with the involvement of medical writers in
      academic environments. 

PMID- 23952981
TI  - [Amitriptyline versus placebo for major depression].
AB  - A recent Cochrane review concluded that amitriptyline is an efficacious
      antidepressant drug, however associated with a number of side effects. The
      present paper discusses this finding in relation to studies on effects and side
      effects of SSRIs and dual-action drugs. It is concluded that there is some
      evidence for recommending treatment with tricyclic antidepressants (TCA)
      especially in patients who are hospitalized with severe depression and
      melancholic features. Further, nortriptylin is preferred due to its more
      favourable side effects profile. 

PMID- 23952982
TI  - [Noninvasive estimation of fibrosis in chronic viral hepatitis].
AB  - In chronic viral hepatitis the liver biopsy helps the clinician to decide when to
      start treatment and plan follow-up. However, the execution of a liver biopsy is
      associated with discomfort, and sampling error can lead to misinterpretation.
      Serum markers and transient elastography (TE) are being considered as surrogates
      to the liver biopsy. The noninvasive tests are considered equal in identifying
      significant fibrosis, but TE is superior in identifying cirrhosis. 

PMID- 23952983
TI  - [Methods for systematic listing of medication in the elderly].
AB  - To improve medication in the elderly several screening tools have been developed.
      The most used tool is the Beers 2003 criteria; however, the newer STOPP/START
      criteria have proven more effective and easier to use. Based on the literature we
      aim to compare these tools according to a list of desired properties and to
      suggest the best template for a Danish tool, though it is still to be determined,
      whether the identification and correction of potentially inappropriate medication
      leads to a better outcome in terms of decreased morbidity and mortality and
      improved health economics. 

PMID- 23952984
TI  - [Pulmonary interstitial emphysema in a 15-month-old child treated with high
      frequency oscillatory ventilation].
AB  - Pulmonary interstitial emphysema (PIE) is a known complication of mechanical
      ventilation of preterm infants. PIE is associated with high mortality and
      treatment is controversial as both surgery and conservative treatment are
      possibilities. We present a case with a 15-month-old previously healthy child,
      hospitalized with severe respiratory distress. A computed tomography (CT) of the
      chest revealed localized PIE. He was successfully treated. 

PMID- 23952985
TI  - [Abdominal trauma and hereditary angioedema].

PMID- 23952986
TI  - Polygonal current model: an effective quantifier of aromaticity on the magnetic
      criterion.
AB  - To explain peculiar effects of electron delocalization on the magnetic response
      of planar cyclic molecules, a basic model that accounts for their actual
      geometrical structure has been developed by integrating the differential Biot
      Savart law. Such a model, based on a single polygonal circuit with ideal
      features, is shown to be applicable to electrically neutral or charged monocyclic
      compounds, as well as linear polycyclic condensed hydrocarbons. Two theoretical
      quantities, easily computed via quantum chemistry codes (the out-of-plane
      components of the magnetizability, xi?, and the magnetic shielding sigma?(h) of
      points P on the symmetry axis orthogonal to the molecular plane, at distance h
      from the center of mass) are shown to be linearly connected, for example, for
      monocyclic structures, via the relationship sigma?(h) = +/-(MU0/2pi)xi?D(h),
      where D(h) is a simple function of geometrical parameters. Equations of this type
      are useful to rationalize scan profiles of magnetic shielding and nucleus
      independent chemical shift along the highest symmetry axis. For a regular
      polygon, D(h) depends approximately on the third inverse power of the distance d
      of the vertices from the center, and xi? is proportional to the area of the
      polygon, that is, ~d(2); hence, the shielding sigma?(0) and the related nucleus
      independent chemical shift NICS?(0) are unsafe quantifiers of magnetotropicity;
      they are biased by a spurious geometrical dependence on d(-1), incorrectly
      exhalting them in cyclic systems with smaller size. A more reliable
      magnetotropicity measure for a cyclic compound, in the presence of a magnetic
      field Bext applied at right angles to the molecular plane, is defined within the
      polygonal current model by the current susceptibility or current strength,
      ?I/?Bext = -xi?/Aeff, expressed in nanoampere per tesla, where Aeff is a properly
      defined area enclosed with the polygonal circuit. An extended numerical test on a
      wide series of mono- and polycyclic compounds and a comparison with corresponding
      ab initio current susceptibilities prove the superior quality of this indicator
      over other commonly employed aromaticity/antiaromaticity benchmarks on the
      magnetic criterion. 

PMID- 23952987
TI  - The utility of isotope-coded protein labeling for prioritization of proteins
      found in ovarian cancer patient urine.
AB  - Urine offers a number of attractive features as a sample type for biomarker
      discovery, including noninvasive sampling, quantity and availability, stability,
      and a narrow dynamic range. In this study we report the first application of
      isotope coded protein labeling (ICPL), coupled with in-solution isoelectric
      fractionation and LC-MALDI-TOF/TOF, to examine and prioritize urinary proteins
      from ovarian cancer patients. Following the definition of stringent exclusion
      criteria a total of 579 proteins were identified with 43% providing quantitation
      data. Protein abundance changes were validated for selected proteins by ESI-Qq
      TOF MS, following which Western blot and immunohistochemical analysis by tissue
      microarray was used to explore the biological relevance of the proteins
      identified. Several established markers (e.g., HE4, osteopontin) were identified
      at increased levels in ovarian cancer patient urine, validating the approach
      used; we also identified a number of potential marker candidates (e.g.,
      phosphatidylethanolamine binding protein 1, cell-adhesion molecule 1) previously
      unreported in the context of ovarian cancer. We conclude that the ICPL strategy
      for identification and relative quantitation of urine proteins is an appropriate
      tool for biomarker discovery studies, and can be applied for the selection of
      potential biomarker candidates for further characterization. 

PMID- 23952988
TI  - [Hypertrophic cardiomyopathy -- modern state of the problem. Issues of
      epidemiology and nomenclature, genetics and pathophysiology, variants of course
      and differential diagnosis].
AB  - The problem of the study of hypertrophic cardiomyopathy (HCM) has preserved its
      actuality because of high prevalence (1:500), risk of sudden cardiac death (SCD)
      in individuals of young able-bodied age. Subject of great interest appear
      problems of search for additional clinical, instrumental and genetic markers,
      environmental factors which are capable to influence formation of a clinical
      variant of HCM course, risk of SCD, and prognosis of HCM. Important problem
      requiring further study appears to be molecular genetic characteristic of the
      disease. Integrated nomenclature of various forms and variants of course of HCM
      is essential for elaboration of tactics of management of patients and assessment
      of results of multicenter trials. 

PMID- 23952989
TI  - [Structural and functional status of arteries in young and middle-aged men with
      ischemic heart disease].
AB  - Aim of the study was to determine whether structural and functional status of
      arteries differ between young and middle-aged men with ischemic heart disease
      (IHD). A total of 78 men aged 28 to 50 years were recruited in this study: 49
      with angiographically proven obstructive atherosclerosis of coronary arteries, 29
      without clinical manifestations of IHD (control group). Those with arterial
      hypertension, diabetes mellitus or marked hypercholesterolemia (LDL cholesterol
      more or equal 4.5 mmol/l) were excluded from the study. All patients underwent
      carotid ultrasound, endothelial function, and arterial stiffness measurements.
      Patients with IHD more often had multiple carotid plaques (86.7% vs 13.7%,
      p<0.001), and increased aortic pulse wave velocity (PWV) assessed by ultrasound
      duplex scanning (53.1% vs. 24.1%, p=0.02). Aortic PWV was related to the severity
      of coronary atherosclerosis. Presence of a carotid intima-media thickness more or
      equal 0.9 mm and abnormal flow-mediated dilatation (FMD) of the brachial artery
      was not significantly different between the groups. 

PMID- 23952990
TI  - [An experience of the use of a curative method of cardiac shock wave therapy in
      patients with ischemic heart disease].
AB  - Aim of the study was to assess effects of cardiac shock wave therapy (CSWT) in
      patients with coronary artery disease (CAD) with refractory stable angina
      pectoris. Seventeen CAD patients with refractory II-IV class angina (3 women and
      14 men, mean age 67.4+/-8.6 years) received the course of 9 procedures of CSWT.
      All patients had I-III New York Heart Association (NYHA) class congestive heart
      failure. Before and after CSWT medical examination with life quality assessment
      by means of the Minnesota Living Questionnaire, echocardiography, veloergometry,
      myocardial perfusion imaging with single-photon emission computed tomography
      (SPECT) using 99M-Tc-methyl-iodine-benzyl-guanydin (MIBG) and Holter ECG
      monitoring was performed. The dynamics of pro-angiogenic factors (VEGF, HGF, FGF
      ) were also measured by ELISA, and of brain natriuretic peptide (Nt-proBNP) by
      the electrochemoluminescence method. Most patients (80%) had significant life
      quality (<0.01) and myocardial perfusion improvement. Episodes of angina pectoris
      and nitrate intake were more than twice decreased. There was a significant
      increase in exercise tolerance (p<0.01). Holter ECG monitoring showed decreasing
      of an average heart rate (p<0.02); no worsening of previous cardiac arrhythmias
      was observed. The significant (p<0.05) decreases in plasma Nt-proBNP and
      increases in VEGF concentration were revealed after CSWT. CSWT procedures were
      well tolerated. The results of our study confirm high effectiveness and safety of
      CSWT in complex treatment of patients with CAD, resistant angina pectoris,
      including patients after myocardial revascularization and with heart failure. 

PMID- 23952991
TI  - [Clinical characteristics of patients and number of stem cells in the myocardium
      of right atrial appendage in patients with ischemic heart disease].
AB  - In the last years stem cells (SC) have been identified in rodent and human
      hearts. These cells have ability to multilineage differentiation in vitro and in
      vivo and improve cardiac function. The development of new methods of isolation SC
      offers new approaches to cardiac regeneration. However, the question of how
      individual patient characteristics influence the number of SC remains unclear. In
      our study we aimed to define the correlation between patient characteristics and
      SC number. Our findings suggest that clinical characteristics and severity of the
      disease may affect the yield of SC in heart tissue. Our data contribute to the
      development of efficient methods for SC isolation for stem cell therapy. 

PMID- 23952992
TI  - [Comparative study of results of coronary angiography in patients with first and
      repetitive myocardial infarction].
AB  - We compared coronary angiography data from 65 patients with first myocardial
      infarction (fMI) and 65 patients with repetitive MI (reMI). Coronary angiographic
      status in both patients with fMI and reMI was characterized by predominance of
      multivessel lesions with stenoses localized in branches of both coronary arteries
      (CA). Contrary to fMI patients with reMI had more severe right CA involvement,
      greater number of occlusions and diffuse lesions in CA bed. Differences between
      angiography data between fMI and reMI were more pronounced in men than in women.
      Angiographic differences between fMI and reMI did not depend on the presence of
      history of arterial hypertension and were considerably attenuated by diabetes
      mellitus. 

PMID- 23952993
TI  - [The multifactorial genesis of left ventricle remodeling in patients with
      essential arterial hypertension].
AB  - We examined 122 patients (70 men and 52 women, mean age 56.17+/-1.4 years) with
      essential hypertension (EH) by echocardiography, radionuclide and radioimmune
      methods. In 43 patients carotid-femoral pulse wave velocity (PWV) was evaluated
      by means of the Complier method. In patients with stage I EH cardiac index was
      significantly increased. This parameter decreased with stabilization of blood
      pressure while total peripheral resistance (TPR) progressively rose. Pulmonary
      blood volume was high and volume of circulating blood was normal. Concentration
      of renin in patients with I-II stages of EH was either normal or high, while in
      patients with stage III EH it was low. The aldosterone level was significantly
      increased in all stages of EH. The prevalent geometric type of left ventricular
      (LV) remodeling in patients with EH was concentric hypertrophy (62.8%). Eccentric
      LV hypertrophy (LVH) was observed in 22.1% of patients. PWV was increased in all
      patients but more apparently in patients with stage III EH. Associations were
      found between PWV and heart rate, hemodynamic, hormonal, cardiac and vascular
      structural parameters. Degrees of these associations depended on stage of EH.
      Conclusion. Genesis of LVH and LV remodeling in patients with EH is
      multifactorial. Hemodynamic and hormonal factors produce double effect on the
      heart inducing volume-dependent and pressure-dependent LVH. 

PMID- 23952995
TI  - [A case of familial hypercholesterolemia caused by a novel mutation p.
      FsS65:D129X of human low density lipoprotein receptor gene].
AB  - Novel mutation p. FsS65:D129X in human low density lipoprotein receptor gene in a
      female patient with typical clinical symptoms of familial hypercholesterolemia is
      described in this paper. Segregation of this mutation with hypercholesterolemia
      in the family of the patient from Petrozavodsk is demonstrated. 

PMID- 23952994
TI  - [Cardiac resynchronization therapy in patients with permanent atrial
      fibrillation].
AB  - In our study we compared effect of cardiac resynchronization therapy (CRT) in
      chronic heart failure (CHF) patients with permanent atrial fibrillation (AF) and
      patients with sinus rhythm. Special feature of our work was that patients with
      permanent atrial fibrillation didnt have obligatory ablation of atrio-ventricular
      node but underwent aggressive rate control to achieve more than 90% of
      biventricular (BV) complexes. We used 24 hours Holter monitoring because there
      are data that this method is more accurate than CRT counters. METHODS: We
      included 30 patients: 21 patients with sinus rhythm and 9 patients with permanent
      AF with ejection fraction <35%, II-IV NYHA class and wide QRS (>120 ms). We
      examined patients before implantation of CRT and after 6 months. RESULTS: mean
      NYHA class decreased from III to II. Distance at 6-min walk test increased by 107
      m in AF group and by 105 in sinus rhythm group. EF increased by 7% in AF group
      and by 6% in sinus rhythm group. Mean time of further observation was 2 years
      (from 10 months to 5 years). There was 1 death (11.1%) in AF group and 3 deaths
      (15%) in sinus rhythm group (p>0,05). CONCLUSION: CRT is effective in CHF
      patients with permanent AF and pharmacological rate control if percent of BV
      pacing is more than 90% on Holter monitoring.

PMID- 23952996
TI  - [Ischemic heart disease complicated by heart failure: possibilities of surgical
      treatment].
AB  - Aim of the study was to assess remote results of surgical reconstruction of the
      left ventricle (LV) in patients with ischemic heart disease (IHD) and chronic
      heart failure (CHF). During 1996-2010 136 patients with IHD complicated by CHD
      were subjected to surgery. The patients were divided into 2 groups: with LV
      aneurism (group 1, n=70) and with ischemic cardiomyopathy (group 2, n=66). In all
      patients we performed coronary bypass surgery and Dor LV reconstruction. Moderate
      and high degree mitral regurgitation was corrected. Hospital mortality was 5.4%
      in group 2. There were no inhospital deaths in group 1. In all survivors we noted
      reduction of LV dimensions and sphericity of LV cavity, increase of LV ejection
      fraction. Ten year survival was 78 and 56,5% in groups 1 and 2, respectively. In
      10 years after surgery 80.2 and 68% of patients, respectively, had no signs of
      high NYHA class (III-IV) CHF. Thus surgical intervention on all components of
      intracardiac pathology in patients with IHD with CHF allowed to achieve
      satisfactory long term results. 

PMID- 23952997
TI  - [Antioxidant properties of apelin-12 and its structural analogue in experimental
      ischemia and reperfusion].
AB  - Effects of apelin-12 H-Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Met-Pro-Phe-OH (A12)
      and its modified analogue H-(NMe)Arg-Pro-Arg-Leu-Ser-His-Lys-Gly-Pro-Nle-Pro-Phe
      OH (I) on activity of antioxidant enzymes, formation of malonic dialdehyde (MDA)
      and generation of reactive oxygen species (ROS) were studied in ex vivo and in
      vivo models of myocardial ischemia and reperfusion (I/R) injury in Wistar rats.
      Preischemic infusion of peptide A12 or AI enhanced cardiac function recovery of
      isolated perfused heart and was accompanied by a marked attenuation of ROS
      generation detected by electron paramagnetic resonance (EPR) technique in
      myocardial effluent at early reperfusion compared with control. Intravenous
      administration (i.v.) of peptides in narcotized rats with regional myocardial
      ischemia limited infarct size and reduced activity of lactate dehydrogenase and
      MB-fraction of creatine kinase in plasma at the end of reperfusion. Treatment
      with peptide A12 prevented reduction or augmented activity of myocardial u/Zn
      superoxide dismutase, catalase and glutathione peroxidase by the end of
      reperfusion in both I/R models compared with control. Increased MDA content in
      the area at risk of rat heart in situ at the end of reperfusion was reduced to
      the initial value under the effect of i.v. A12 administration. Therefore,
      cardioprotective action of natural apelin-12 and its structural analog AI involve
      reduction of short-lived ROS generation and improvement of the antioxidant state
      of ischemic heart during reperfusion. 

PMID- 23952998
TI  - [Nicorandil in the treatment of patients with ischemic heart disease].
AB  - Adequate drug therapy of stable ischemic heart disease directed at reduction and
      prevention of main clinical symptoms of the disease, increase of exercise
      tolerance to physical effort, improvement of quality of life and prognosis
      remains an actual problem. Nicorandil combines properties of an antianginal drug
      and cardioprotective effects. Its pharmacological action is related to
      capabilities to be an nitrous oxide donor and to activate ATP-dependent potassium
      channels. In this review we present data on mechanism of action of nicorandil, on
      its clinical effectiveness, and on comparison with antianginal drugs of other
      groups. We have also analyzed experience of the use of nicorandil in patients
      with acute coronary syndrome and in conjunction with during invasive
      interventions. 

PMID- 23952999
TI  - [LINKOR: results of observational program in patients with myocardial
      infarction].
AB  - The results of Assessment Program effective treatment of patients with myocardiaL
      INfarction drug ProCORalan (ivabradine) in outpatient practice, conducted in 53
      cities of the Russian Federation, 333 doctors. Included 1226 patients (822 men
      and 404 women, average age 60,1+/-9,3 years). Despite treatment, before inclusion
      in the patients maintained an average 8,17+/-8,60 (mediana 6) angina attacks per
      week, elevated blood pressure (141,8+/-20,3/86,2+/-11,6 mm Hg) and heart rate
      (84,5 +/-10,4 beats / min). Adding to ivabradine treatment for 16 weeks resulted
      in significant (p<0.00001) reduction in heart rate (up to 63,1+/-7,5 beats /
      min), the number of angina attacks per week (from 8.17 to 1.27) and need for
      nitroglycerin (from 7.69 to 0.89 tablets per week). Decreased the number of
      patients that called ambulance assistance (from 35.6 to 1.5%), and
      hospitalization (from 15.4 to 1.2%). There was a significant (p<0.00001) increase
      in evaluating the effectiveness of treatment (from 5,4+/-1,8 to 8,9 +/-1,3
      points), reducing the risk stratification of patients (6,1+/-1,5 to 4 3+/-2,0
      points), increased stability evaluation of state (from 5,6+/-1,9 to 3,7+/-2,2
      points) and improved assessment of prognosis (from 5,7+/-2,0 to 3,6 +/-1,9
      points). Expressed significantly positive effects observed after 1 month of
      therapy, after the effect became more pronounced. Significantly improved quality
      of life estimated by Seattle Angina Questionnaire and Minnesota Living with Heart
      Failure. The maximum recommended dose ivabradine of 15mg/day were given 50% of
      the patients, the dose of 10 mg/day - 28%. Adverse effects were reported in 3.3%
      of patients, of which, according to doctors associated with taking the drug -
      0.82%. During follow up, 4 patients died. Thus, the addition of ivabradine to 
      blocker therapy, persons with a history of myocardial infarction and angina
      experiencing elevated heart rate, are the tactics of a rational and safe therapy.

PMID- 23953000
TI  - [Original medicines and generics: an analysis of efficacy and safety via
      controlled studies and using the register on the example of amlodipine].

PMID- 23953001
TI  - [Pathogenetic significance of hyperuricemia in the formation and development of
      pathological processes associated with metabolic syndrome].
AB  - This literature review allows to consider hyperuricemia as an important link in
      pathogenesis of cardiorenovascular pathologies, gout, diabetes, etc. The review
      contains detailed analysis of mechanisms of development of pathological processes
      caused by hyperuricemia, presentation of factors promoting elevation of uric acid
      level and description of direct effect of uric acid on organs and tissues. 

PMID- 23953002
TI  - [A case of severe intravascular hemolysis after double mechanical heart valve
      implantation].
AB  - A case report of a patient with a triple cardiac valve replacement complicated by
      severe postoperative intravascular hemolysis is presented. The patient had
      neither prosthetic valvular dysfunction nor paravalvular leak and had an
      excellent hemodynamic response to the operation. Replacement of the aortic and
      mitral prostheses with stented porcine prosthesis alleviated the problem. 

PMID- 23953003
TI  - Observation of nonlinear dissipation in piezoresistive diamond nanomechanical
      resonators by heterodyne down-mixing.
AB  - We report the observation of nonlinear dissipation in diamond nanomechanical
      resonators measured by an ultrasensitive heterodyne down-mixing piezoresistive
      detection technique. The combination of a hybrid structure as well as symmetry
      breaking clamps enables sensitive piezoresistive detection of multiple orthogonal
      modes in a diamond resonator over a wide frequency and temperature range. Using
      this detection method, we observe the transition from purely linear dissipation
      at room temperature to strongly nonlinear dissipation at cryogenic temperatures.
      At high drive powers and below liquid nitrogen temperatures, the resonant
      structure dynamics follows the Pol-Duffing equation of motion. Instead of using
      the broadening of the full width at half-maximum, we propose a nonlinear
      dissipation backbone curve as a method to characterize the strength of nonlinear
      dissipation in devices with a nonlinear spring constant. 

PMID- 23953005
TI  - What's in a name? Expiratory tracheal narrowing in adults explained.
AB  - Tracheomalacia, tracheobronchomalacia, and excessive dynamic airway collapse are
      all terms used to describe tracheal narrowing in expiration. The first two
      describe luminal reduction from cartilage softening and the latter refers to
      luminal reduction from exaggerated posterior membrane movement. Expiratory
      tracheal narrowing is a frequent occurrence that can cause symptoms of airway
      obstruction, such as dyspnoea, wheeze, and exercise intolerance. The accurate
      diagnosis and quantification of expiratory tracheal narrowing has important
      aetiological, therapeutic, and prognostic implications. The reference standard
      for diagnosis has traditionally been bronchoscopy; however, this method has
      significant limitations. Expiratory tracheal disorders are readily detected by
      four-dimensional dynamic volume multidetector computed tomography (4D-CT), an
      emerging, non-invasive method that will potentially enable detection and
      quantification of these conditions. This review discusses the morphological forms
      of expiratory tracheal narrowing and demonstrates the utility of 4D-CT in the
      diagnosis, quantification, and treatment of these important conditions. 

PMID- 23953004
TI  - Vertebroplasty: Patient and treatment variations studied through parametric
      computational models.
AB  - BACKGROUND: Vertebroplasty is increasingly used in the treatment of vertebral
      compression fractures. However there are concerns that this intervention may lead
      to further fractures in the adjacent vertebral segments. This study was designed
      to parametrically assess the influence of both treatment factors (cement volume
      and number of augmentations), and patient factors (bone and disc quality) on the
      biomechanical effects of vertebroplasty. METHODS: Specimen-specific finite
      element models of two experimentally-tested human three-vertebral-segments were
      developed from CT-scan data. Cement augmentation at one and two levels was
      represented in the respective models and good agreement in the predicted
      stiffness was found compared to the corresponding experimental specimens.
      Parametric variations of key variables associated with the procedure were then
      studied. FINDINGS: The segmental stiffness increased with disc degeneration, with
      increasing bone quality and to a lesser extent with increasing cement volume.
      Cement modulus did not have a great influence on the overall segmental stiffness
      and on the change in the elemental stress in the adjoining vertebrae. However,
      following augmentation, the stress distribution in the adjacent vertebra changed,
      indicating possible load redistribution effects of vertebroplasty.
      INTERPRETATION: This study demonstrates the importance of patient factors in the
      outcomes of vertebroplasty and suggests that these may be one reason for the
      variation in clinical results.

PMID- 23953006
TI  - Multimodality imaging of benign and malignant male breast disease.
AB  - With the increasing use of advanced imaging techniques, male breast lesions are
      being visualized using techniques other than mammography and ultrasound. This
      review illustrates benign and malignant male breast disease on both conventional
      imaging as well as advanced imaging methods including computed tomography,
      magnetic resonance imaging, and positron-emission tomography in order to
      familiarize the radiologist with typical imaging appearances and review the
      proper clinical management. 

PMID- 23953007
TI  - Intra-abdominal fibromatosis: differentiation from gastrointestinal stromal
      tumour based on biphasic contrast-enhanced CT findings.
AB  - AIM: To identify the computed tomography (CT) criteria that differentiate intra
      abdominal fibromatosis (IAF) from gastrointestinal stromal tumour (GIST).
      MATERIALS AND METHODS: CT images of 34 pathologically proven cases of IAF (n =
      15) and GIST (n = 19) were retrospectively reviewed. Location, contour, border,
      enhancement pattern, presence of necrosis, vessels, and air within the lesion
      were analysed. Long diameter (LD), short diameter (SD), LD/SD ratio, degree of
      enhancement, and lesion/aorta (L/A) CT attenuation ratio were measured and
      calculated. Significant CT criteria were identified using Fisher's exact test,
      grouped t-test, and receiver operating characteristic (ROC) curve. Sensitivity
      and specificity values were calculated when single or multiple CT criteria were
      used. RESULTS: Extra-gastrointestinal location, ovoid or irregular contour,
      homogeneous enhancement, absence of intra-lesional necrosis, lower degree of
      enhancement, and L/A CT attenuation ratio differentiated IAF from GIST (p <
      0.05). When any three of these eight criteria were combined, the sensitivity and
      specificity for diagnosing IAF were 100% (15 of 15) and 89.5% (17 of 19),
      respectively. CONCLUSION: The following eight CT criteria are helpful to
      differentiate IAF from GIST: extra-gastrointestinal location, ovoid or irregular
      contour, homogeneous enhancement, absence of intra-lesional necrosis, a degree of
      enhancement of less than 40.5 HU in the arterial phase versus 46.5 HU in the
      portal venous phase, and an L/A CT attenuation ratio <0.315 in the arterial phase
      versus 0.525 in the portal phase.

PMID- 23953008
TI  - From feedback inhibition to allostery: the enduring example of aspartate
      transcarbamoylase.
AB  - Aspartate transcarbamoylase (ATCase) of Escherichia coli, the first enzyme of the
      pyrimidine biosynthetic pathway, is inhibited by CTP and UTP, the nucleotide end
      products of the pathway. First discovered by Yates and Pardee in 1956 [Yates R &
      Pardee AB (1956) J Biol Chem 221, 743-756; Yates RA & Pardee AB (1956) J Biol
      Chem 221, 757-770], these interactions establish feedback inhibition in vivo, a
      key means of metabolic regulation by which end-product production by the pathway
      is adjusted to end-product usage in macromolecule synthesis. Activation of the
      enzyme by the purine nucleotide ATP may also have regulatory significance. ATCase
      and threonine deaminase of E. coli were the first enzymes to be characterized
      with regard to their allosteric properties, namely, sigmoidal saturation with
      regard to substrates, reflecting cooperative ligand binding at the active site,
      and inhibition and activation by nucleotides of very different chemical structure
      from the substrates. In the case of ATCase, the nucleotides bind at regulatory
      sites located on protein subunits different from those bearing the active sites.
      The early characterization of ATCase proved useful in the 1965 conceptualization
      of the allosteric transition by Monod, Wyman, and Changeux [Monod J et al. (1965)
      J Mol Biol 12, 88-118], and the protein in subsequent years has proved useful in
      the experimental analysis of the interactions of sites and of conformational
      changes in allosteric proteins. This is an account of the early years of work on
      ATCase, up to 1965.

PMID- 23953009
TI  - Fresh frozen cadaver workshops for advanced vascular surgical training.
AB  - BACKGROUND: Reduction in working hours, streamlined training schemes and
      increasing use of endovascular techniques has meant a reduction in operative
      experience for newer vascular surgical trainees, especially those exposures which
      are not routinely performed such as thoracoabdominal, thoracotomy and
      retroperitoneal aortic, for example. METHODS: This paper describes an Advanced
      Anatomy of Exposure course which was designed and convened at the Clinical
      Training & Evaluation Centre in Western Australia and uses fresh frozen cadavers.
      Feedback was obtained from the participants who attended over three courses by
      questionnaire. RESULTS: Feedback was strongly positive for the course meeting
      both its learning outcomes and personal learning objectives, and in addition,
      making a significant contribution to specialty skills. Most participants thought
      the fresh frozen cadaveric model significantly improved the learning objectives
      for training. CONCLUSIONS: The fresh frozen cadaver is an excellent teaching
      model highly representative of the living open surgical scenario where advanced
      trainees and newly qualified consultants can improve their operative confidence
      and consequently patient safety in vascular surgery. An efficient fresh frozen
      cadaver teaching programme can benefit many health professionals simultaneously
      maximizing the use of donated human tissue.

PMID- 23953010
TI  - Hyperbaric oxygen improves engraftment of ex-vivo expanded and gene transduced
      human CD34+ cells in a murine model of umbilical cord blood transplantation.
AB  - Delayed engraftment and graft failure represent major obstacles to successful
      umbilical cord blood (UCB) transplantation. Herein, we evaluated the use of
      hyperbaric oxygen (HBO) therapy as an intervention to improve human UCB
      stem/progenitor cell engraftment in an immune deficient mouse model. Six- to
      eight-week old NSG mice were sublethally irradiated 24 hours prior to CD34+ UCB
      cell transplant. Irradiated mice were separated into a non-HBO group (where mice
      remained under normoxic conditions) and the HBO group (where mice received 2
      hours of HBO therapy; 100% oxygen at 2.5 atmospheres absolute). Four hours after
      completing HBO therapy, both groups intravenously received CD34+ UCB cells that
      were transduced with a lentivirus carrying luciferase gene and expanded for in
      vivo imaging. Mice were imaged and then sacrificed at one of 10 times up to 4.5
      months post-transplant. HBO treated mice demonstrated significantly improved bone
      marrow, peripheral blood, and spleen retention and subsequent engraftment. In
      addition, HBO significantly improved peripheral, spleen and bone marrow
      engraftment of human myeloid and B-cell subsets. In vivo imaging demonstrated
      that HBO mice had significantly higher ventral and dorsal bioluminescence values.
      These studies suggest that HBO treatment of NSG mice prior to UCB CD34+ cell
      infusion significantly improves engraftment.

PMID- 23953011
TI  - Nursing students' experiences of involvement in clinical research: an exploratory
      study.
AB  - BACKGROUND: Nursing education can positively affect nurses' attitudes toward
      nursing research, resulting in better patient outcomes. Experiential learning
      theory was the basis for this study. OBJECTIVES: To explore nursing students'
      experiences of involvement in clinical research, their approach to learning and
      their interest in nursing research. DESIGN: Cross-sectional. METHODS: One hundred
      and twenty-six nursing students were invited to be involved as data collectors in
      a research project as part of their training in research methodology. The
      students completed an evaluation form and the Revised Study Process
      Questionnaire. The questionnaires were analyzed quantitatively and one open-ended
      question was analyzed qualitatively. RESULTS: On the whole, the students were
      happy to be involved in the data collection although a minority felt uncertain
      and exposed. Students with a deeper approach to learning felt that their
      involvement had increased their interest in nursing research and they stated that
      data collection should be a regular feature of the course. CONCLUSIONS:
      Participation as data collectors in research has the potential to increase
      interest in nursing research among students with higher levels of deep learning.
      Further studies are needed to examine ways to increase interest in research among
      students with lower levels of deep learning.

PMID- 23953012
TI  - Dr. Frances A. Hellebrandt: pioneering physiologist, physiatrist, and physical
      medicine and rehabilitation program visionary.

PMID- 23953013
TI  - The Multicenter Osteoarthritis Study: opportunities for rehabilitation research.

PMID- 23953015
TI  - The role of cognitive behavioral therapy for chronic pain in adolescents.
AB  - Chronic pain is frequently experienced in adolescents; it affects functionality
      and requires interventions to decrease the impairments caused by pain. Cognitive
      behavioral therapy (CBT) has been analyzed in numerous studies that evaluated its
      effects on reducing the different types of chronic pain in children and
      adolescents. Interestingly, the outcome of CBT was initially focused on pain
      intensity, but, because there is no correspondence between children's pain
      intensity and level of disability, the ability to participate in school and
      social and recreational activities have been the primary focus of recent studies.
      There are innovative methods of CBT (such as the third generation of CBT) with
      and without the use of technology that facilitates the availability of this
      psychological treatment to adolescents with chronic pain, optimizing its
      accessibility and comprehensiveness, and maintaining its effectiveness. In the
      future, specific types of CBT could be specific to the diagnosis of chronic pain
      in the adolescent, sociodemographics, and other unique features. Parents of
      children with chronic pain are usually included in these programs, either as
      coaches in the intervention or as recipients of psychological therapies
      (including CBT) to optimize benefits. CBT has no adverse effect on chronic pain
      in adolescents, and there is no literature that makes reference to the
      effectiveness of CBT in preventing chronic pain in adolescents. A review of the
      role of CBT in chronic pain in adolescents via a PubMed database search was
      performed to identify the role of CBT in the management of chronic pain in
      adolescents. 

PMID- 23953016
TI  - A systematic review to assess comparative effectiveness studies in epidural
      steroid injections for lumbar spinal stenosis and to estimate reimbursement
      amounts.
AB  - OBJECTIVE: To systematically appraise published comparative effectiveness
      evidence (clinical and economic) of epidural steroid injections (ESI) for lumbar
      spinal stenosis and to estimate Medicare reimbursement amounts for ESI
      procedures. TYPE: Systematic review. LITERATURE SURVEY: PubMed, Embase, and
      CINAHL were searched through August 2012 for key words that pertain to low back
      pain, spinal stenosis or sciatica, and epidural steroid injection. We used
      institutional and Medicare reimbursement amounts for our cost estimation.
      Articles published in English that assessed ESIs for adults with lumbar spinal
      stenosis versus a comparison intervention were included. Our search identified
      146 unique articles, and 138 were excluded due to noncomparative study design,
      not having a study population with lumbar spinal stenosis, not having an
      appropriate outcome, or not being in English. We fully summarized 6 randomized
      controlled trials and 2 large observational studies. METHODOLOGY: Randomized
      controlled trial articles were reviewed, and the study population, sample size,
      treatment groups, ESI dosage, ESI approaches, concomitant interventions,
      outcomes, and follow-up time were reported. Descriptive resource use estimates
      for ESIs were calculated with use of data from our institution during 2010 and
      Medicare-based reimbursement amounts. SYNTHESIS: ESIs or anesthetic injections
      alone resulted in better short-term improvement in walking distance compared with
      control injections. However, there were no longer-term differences. No
      differences between ESIs versus anesthetic in self-reported improvement in pain
      were reported. Transforaminal approaches had better improvement in pain scores
      (<=4 months) compared with interlaminar injections. Two observational studies
      indicated increased rates of lumbar ESI in Medicare beneficiaries. Our sample
      included 279 patients who received at least 1 ESI during 2010, with an estimated
      mean total outpatient reimbursement for one ESI procedure "event" to be $637,
      based on 2010 Medicare reimbursement amounts ($505 technical and $132
      professional payments). CONCLUSION: This systematic review of ESI for treating
      lumbar spinal stenosis found a limited amount of data that suggest that ESI is
      effective in some patients for improving select short-term outcomes, but results
      differed depending on study design, outcome measures used, and comparison groups
      evaluated. Overall, there are relatively few comparative clinical or economic
      studies for ESI procedures for lumbar spinal stenosis in adults, which indicated
      a need for additional evidence.

PMID- 23953017
TI  - Regulatory changes are upon us.

PMID- 23953018
TI  - ACGME sports, ACGME pain, or non-ACGME sports and spine: which is the ideal
      fellowship training for PM&R physicians interested in musculoskeletal medicine?

PMID- 23953019
TI  - Diagnosis and treatment of abductor hallucis focal dystonia with botulinum toxin
      injection: a case presentation.

PMID- 23953020
TI  - Avulsion fracture of the anterior inferior iliac spine in a soccer player.

PMID- 23953021
TI  - Re: correlation of paraspinal atrophy and denervation in back pain and spinal
      stenosis relative to asymptomatic controls.

PMID- 23953022
TI  - Working conditions, serotonin transporter gene polymorphism (5-HTTLPR) and
      anxiety disorders: a prospective cohort study.
AB  - BACKGROUND: The etiology and pathology of anxiety disorders involve both genetic
      and environmental influences. Adverse working conditions may contribute to the
      development of anxiety. The serotonin transporter-linked polymorphic region (5
      HTTLPR) has been implicated in stress sensitivity. Therefore, we investigated the
      potential interplay between 5-HTTLPR and job-related risk factors in the
      prediction of the occurrence of anxiety. METHODS: We conducted a prospective
      study using the first two waves of a Swedish population-based cohort. At Wave I,
      1585 individuals without anxiety, depression or dysthymia who were active in the
      labor market during both waves were included. Information on job demands, skill
      discretion, decision authority and social climate was collected at Wave I. After
      a three year interval, the presence of anxiety disorders was determined at Wave
      II. All 1585 participants were genotyped for 5-HTTLPR. Both additive and
      multiplicative models were considered in examining the potential interaction
      between 5-HTTLPR and adverse working conditions on the development of anxiety.
      RESULTS: Anxiety was associated with high job demands but not with 5-HTTLPR. An
      interaction was observed between 5-HTTLPR and high job demands among females.
      Individuals with 5-HTTLPR high expression genotype (LL) developed anxiety
      disorders more frequently when exposed to high job demands compared to 'LS/SS'
      carriers. LIMITATIONS: A limited number of participants developed anxiety.
      CONCLUSIONS: High job demands predict the development of anxiety. The 5-HTT
      polymorphism has a moderating effect on the relationship between high job demands
      and anxiety among females.

PMID- 23953024
TI  - Predictors and moderators of response to internet-delivered Interpersonal
      Psychotherapy and Cognitive Behavior Therapy for depression.
AB  - BACKGROUND: By identifying which predictors and moderators lead to beneficial
      outcomes, accurate selection of the best initial treatment will have significant
      benefits for depressed individuals. METHOD: An automated, fully self-guided
      randomized controlled internet-delivered noninferiority trial was conducted
      comparing two new interventions (Interpersonal Psychotherapy [IPT; n=620] and
      Cognitive Behavioral Therapy [CBT; n=610]) to an active control intervention
      (MoodGYM; n=613) over a period of 4 weeks to spontaneous visitors of an internet
      delivered therapy website (e-couch). A range of putative predictors and
      moderators (socio-demographic characteristics [age, gender, marital status,
      education level], clinical characteristics [depression/anxiety symptoms,
      disability, quality of life, medication use], skills [mastery and dysfunctional
      attitudes] and treatment preference) were assessed using internet-delivered self
      report measures at baseline and immediately following treatment and at six months
      follow-up. Analyses were conducted using Mixed Model Repeated Measures (MMRM).
      RESULTS: Female gender, lower mastery and lower dysfunctional attitudes predicted
      better outcome at post-test and/or follow-up regardless of intervention. No
      overall differential effects for condition on depression as a function of outcome
      were found. However, based on time-specific estimates, a significant interaction
      effect of age was found. For younger people, internet-delivered IPT may be the
      preferred treatment choice, whereas older participants derive more benefits from
      internet-delivered CBT programs. LIMITATIONS: Although the sample of participants
      was large, power to detect moderator effects was still lacking. CONCLUSIONS:
      Different e-mental health programs may be more beneficial for specific age
      groups. The findings raise important possibilities for increasing depression
      treatment effectiveness and improving clinical practice guidelines for depression
      treatment of different age groups.

PMID- 23953025
TI  - Three-dimensional speckle tracking echocardiography for the evaluation of the
      infarct size and segmental transmural involvement in patients with acute
      myocardial infarction.
AB  - PURPOSE: To compare parameters between three-dimensional speckle tracking
      echocardiography (3DSTE) and delayed enhancement magnetic resonance imaging (DE
      MRI) for estimating myocardial infarct size, peak systolic strain, and transmural
      involvement of infarct segments in patients with acute myocardial infarction
      (AMI). METHODS: Delayed enhancement MRI was conducted to determine myocardial
      infarction (MI) position, size, and transmural involvement in 26 patients with
      AMI. 3DSTE was conducted to measure global peak systolic strain in the left
      ventricle and to estimate longitudinal, circumferential, and radial peak systolic
      strain in papillary muscle segments. Conventional echocardiography was used to
      calculate the wall-motion score index (WMSI) and left ventricular ejection
      fraction (LVEF). RESULTS: Left ventricular strain parameters and LVEF were
      statistically significantly lower in patients with large-size MI than in those
      with small-size MI. Global longitudinal strain (GLS) and global circumferential
      strain (GCS) were significantly lower in patients with moderate-size MIs than in
      those with small-size MIs. All parameters except ejection fraction (EF) were
      lower in patients with large-size MI compared with those with moderate-size MI (P
      < 0.05). Pearson analysis revealed that left ventricular GCS, GLS, GRS, WMSI, and
      LVEF of AMI patients correlated with the myocardial infarct area (MIA) measured
      by MRI (r = 0.86, 0.81, -0.71, 0.64, and -0.66, respectively; all P-values
      <0.01). Transmural infarct segments exhibited significantly lower longitudinal,
      circumferential, and radial strains than normal segments (P < 0.05). CONCLUSIONS:
      These findings indicate that 3DSTE can distinguish between MIs of different
      infarct sizes, and may provide an indirect means for the accurate determination
      of transmural involvement in infarct segments.

PMID- 23953026
TI  - Variable interference with interferon signal transduction by different strains of
      porcine reproductive and respiratory syndrome virus.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-sense
      single-strand RNA virus that has contributed to substantial losses to the swine
      industry. The objective of this study was to examine the interference of
      interferon (IFN)-activated signaling by PRRSV viral proteins and compare the
      effects of several PRRSV strains on the IFN signaling. Three non-structural
      proteins (nsp 1beta, 7 and 12) and two structural proteins (GP3 and N) of VR-2385
      were found to significantly inhibit the expression of IFN-stimulated response
      element (ISRE) luciferase reporter. Nsp1beta and N showed robust inhibition and
      their-encoding sequences from the six PRRSV strains (VR-2385, Ingelvac PRRS MLV,
      VR-2332, NVSL97-7895, MN184, and Lelystad) were cloned for further
      characterization. The nsp1betas of all the strains except MLV inhibited
      expression of IFN-induced ISRE reporter, interferon-stimulated gene 56 (ISG56)
      and signal transducer and activator of transcription 2 (STAT2). The N proteins
      inhibited the IFN-induced ISRE reporter expression and STAT2 elevation and
      blocked nuclear translocation of STAT1. In MARC-145 cells, all the six PRRSV
      strains with the exception of MN184 blocked the activity of exogenous IFN-alpha.
      In primary porcine pulmonary alveolar macrophages (PAMs), only MLV and NVSL
      failed to inhibit the activity of IFN-alpha. These results indicate that some
      PRRSV strains, such as NVSL and MN184, have variable effects on IFN-activated
      signaling in the two types of cells.

PMID- 23953027
TI  - Complete sequence of the multi-resistance plasmid pV7037 from a porcine
      methicillin-resistant Staphylococcus aureus.
AB  - The aim of this study was to determine the complete sequence of the multi
      resistance plasmid pV7037 to gain insight into the structure and organization of
      this plasmid. Of the four XbaI clones of pV7037, one clone of 17,577 bp has
      already been sequenced and shown to carry a multi-resistance gene cluster. The
      remaining three clones of approximately 12.5, 6.5 and 4.5 kb were sequenced, the
      entire plasmid sequence correctly assembled and investigated for reading frames.
      In addition, two reading frames one coding for an ABC transporter and the other
      coding for an rRNA methylase were cloned and expressed in a S. aureus host to see
      whether they confer antimicrobial resistance properties. Plasmid pV7037 proved to
      be 40,971 bp in size. Besides the previously determined resistance gene cluster,
      it carried a functionally active tet(L) gene for tetracycline resistance, a
      complete cadDX operon for cadmium resistance and also a variant of the beta
      lactamase transposon Tn552. Two single bp deletions, which resulted in frame
      shifts, functionally deleted the genes for the BlaZ beta-lactamase and the signal
      transducer protein BlaR1 in this Tn552 variant of pV7037. Plasmid pV7037 seems to
      be composed of various parts previously known from plasmids and transposons of
      staphylococci and other Gram-positive bacteria. However, there are also parts of
      the plasmid which do not show any homology to so far known sequences deposited in
      the databases. The novel ABC transporter and rRNA methylase genes identified on
      pV7037 do not seem to play a role in antimicrobial resistance. The co-location of
      numerous antimicrobial resistance genes bears the risk of co-transfer and co
      selection of resistance genes, but also persistence of resistance genes even if
      no direct selective pressure by the use of the respective antimicrobial agents is
      applied.

PMID- 23953023
TI  - Depression impairs learning, whereas the selective serotonin reuptake inhibitor,
      paroxetine, impairs generalization in patients with major depressive disorder.
AB  - To better understand how medication status and task demands affect cognition in
      major depressive disorder (MDD), we evaluated medication-naive patients with MDD,
      medicated patients with MDD receiving the selective serotonin reuptake inhibitors
      (SSRI) paroxetine, and healthy controls. All three groups were administered a
      computer-based cognitive task with two phases, an initial phase in which a
      sequence is learned through reward-based feedback (which our prior studies
      suggest is striatal-dependent), followed by a generalization phase that involves
      a change in the context where learned rules are to be applied (which our prior
      studies suggest is hippocampal-region dependent). Medication-naive MDD patients
      were slow to learn the initial sequence but were normal on subsequent
      generalization of that learning. In contrast, medicated patients learned the
      initial sequence normally, but were impaired at the generalization phase. We
      argue that these data suggest (i) an MDD-related impairment in striatal-dependent
      sequence learning which can be remediated by SSRIs and (ii) an SSRI-induced
      impairment in hippocampal-dependent generalization of past learning to novel
      contexts, not otherwise seen in the medication-naive MDD group. Thus, SSRIs might
      have a beneficial effect on striatal function required for sequence learning, but
      a detrimental effect on the hippocampus and other medial temporal lobe structures
      is critical for generalization.

PMID- 23953029
TI  - Raising awareness about hygiene behavior education for nursing assistants in
      China.

PMID- 23953028
TI  - Virulence genotypes of Escherichia coli canine isolates from pyometra, cystitis
      and fecal origin.
AB  - Pyometra is the most common diestrual uterine disease of bitches. Escherichia
      coli is the most frequent bacterium isolated from the uterine content of pyometra
      uteri and it is associated with the most severe clinical signs, leading to
      endotoxemia and sepsis. In this study, canine E. coli isolates from pyometra
      (n=31), cystitis (n=23) and fecal (n=26) origin were compared regarding the
      prevalence of 23 potential virulence traits (15 virulence factor (VF) genes and 8
      pathogenicity associated islands-PAIs), detected by PCR assays. Overall, there
      was a considerable overlap between pyometra, cystitis and fecal isolates
      regarding the phylogenetic grouping and virulence traits. Virulence traits more
      prevalent in pyometra than in cystitis and fecal isolates included two PAIs (PAI
      IV536 and PAI ICFT073) and three VF genes (sfa/focDE, fyuA and chuA). Regardless
      the isolates' origin, the average number of virulence traits per strain was
      higher in B2 than in the other phylogenetic groups (A, B1 and D). The prevalence
      of phylogenetic group B2 was significantly higher in pyometra (94%) than in
      cystitis (48%) and fecal (39%) isolates. In conclusion, pyometra isolates have a
      high potential of virulence and a broad virulence genotype, although being
      similar to a subset of cystitis and fecal isolates. This leads to the suggestion
      that cystitis and fecal isolates may be able to induce pyometra in receptive
      hosts. 

PMID- 23953031
TI  - Dietary patterns and cardiovascular disease.
AB  - Despite strong prospective epidemiology and mechanistic evidence for the benefits
      of certain micronutrients in preventing CVD, neutral and negative outcomes from
      secondary intervention trials have undermined the efficacy of supplemental
      nutrition in preventing CVD. In contrast, evidence for the positive impact of
      specific diets in CVD prevention, such as the Dietary Approaches to Stop
      Hypertension (DASH) diet, has focused attention on the potential benefits of
      whole diets and specific dietary patterns. These patterns have been scored on the
      basis of current guidelines for the prevention of CVD, to provide a quantitative
      evaluation of the relationship between diet and disease. Using this approach,
      large prospective studies have reported reductions in CVD risk ranging from 10 to
      60% in groups whose diets can be variously classified as 'Healthy', 'Prudent',
      Mediterranean' or 'DASH compliant'. Evaluation of the relationship between
      dietary score and risk biomarkers has also been informative with respect to
      underlying mechanisms. However, although this analysis may appear to validate
      whole-diet approaches to disease prevention, it must be remembered that the
      classification of dietary scores is based on current understanding of diet
      disease relationships, which may be incomplete or erroneous. Of particular
      concern is the limited number of high-quality intervention studies of whole
      diets, which include disease endpoints as the primary outcome. The aims of this
      review are to highlight the limitations of dietary guidelines based on nutrient
      specific data, and the persuasive evidence for the benefits of whole dietary
      patterns on CVD risk. It also makes a plea for more randomised controlled trials,
      which are designed to support food and whole dietary-based approaches for
      preventing CVD.

PMID- 23953030
TI  - A randomised phase III trial of the pharmacokinetic biomodulation of irinotecan
      using oral ciclosporin in advanced colorectal cancer: results of the Panitumumab,
      Irinotecan & Ciclosporin in COLOrectal cancer therapy trial (PICCOLO).
AB  - BACKGROUND: The main toxicity of irinotecan in advanced colorectal cancer (CRC)
      is delayed diarrhoea. Intestinal SN-38, released by deconjugation of the parent
      glucuronide excreted into the bile or produced in situ by intestinal
      carboxylesterase, is toxic to the intestinal epithelium. The canalicular
      transport of irinotecan and SN-38G is mediated by ABCC2 (MRP2) and ABCB1 (MDR1)
      which are both inhibited by ciclosporin. We tested whether irinotecan and
      ciclosporin was non-inferior for anti-cancer efficacy and superior for toxicity
      compared with single-agent irinotecan. METHODS: Six hundred and seventy-two
      patients with advanced, measurable CRC following prior fluoropyrimidine
      containing chemotherapy were randomised to either irinotecan 3-weekly 350 mg/m(2)
      (or 300 mg/m(2) if age >70 or performance status (PS)=2) or 3-weekly irinotecan
      at 140 mg/m(2) (120 mg/m(2) if age >70 or PS=2) with ciclosporin 3mg/kg t.d.s.
      for three days by mouth starting on the morning before irinotecan. The primary
      end-point was the proportion of patients alive and progression-free at 12 weeks.
      The key secondary end-point was the incidence of grade >=3 diarrhoea within 12
      weeks of randomisation. RESULTS: The proportion of patients progression-free at
      12 weeks with irinotecan was 53.4% compared to 47.2% with irinotecan plus
      ciclosporin (difference=-6.3%, 95% confidence interval (CI) [-13.8%, 1.3%]).
      Since the lower limit of the 95% CI crossed the pre-specified non-inferiority
      margin of -10.6%, non-inferiority of irinotecan plus ciclosporin compared to
      irinotecan alone was not statistically demonstrated. 15.0% patients developed
      severe diarrhoea on irinotecan compared to 13.8% on irinotecan plus ciclosporin,
      a non-significant difference. INTERPRETATION: The pharmacokinetic biomodulation
      of irinotecan using oral ciclosporin does not improve the therapeutic index of
      irinotecan in advanced CRC. FUNDING: The trial was funded by Cancer Research UK
      and supported by Amgen Pharma.

PMID- 23953032
TI  - PK modulation of peptides by hapten-mediated antibody complexation.

PMID- 23953033
TI  - Management of traumatic hemipelvectomy: an institutional experience on four
      consecutive cases.
AB  - BACKGROUND AND OBJECTIVE: The incidence of traumatic hemipelvectomy is rare, but
      it is a devastating injury. Recently, an increasing number of patients with
      traumatic hemipelvectomy are admitted to trauma centers alive due to improvements
      of the pre-hospital care. Successful management requires prompt recognition of
      the nature of this injury and meticulous surgical technique. We present our
      successful experiences on four cases of traumatic hemipelvectomy in the past nine
      years. PATIENTS AND METHODS: Four cases with traumatic hemipelvectomy were
      admited to our hospital from June 21, 2002 to September 3, 2011. All injuries
      occurred due to vehicle accident and all patients were in a state of severe
      hypotension, with two of them having anal lacerations. These four cases were
      treated immediately with resuscitation, control of hemorrhage, early amputation,
      repeated debridement and closure of the wounds. An angiographic embolization was
      given to control hemorrhage in two of the cases preoperatively. One case
      underwent fecal diversion. Wound infection occurred in all of cases which was
      successfully controlled by repeated debridements, effective anti-biotic regimen,
      split-thickness skin grafts. RESULTS: All four cases were saved successfully with
      well-healed wounds during follow up from 1 to 7 years. They were able to walk by
      themself using crutches. CONCLUSION: Adhering to the surgery principles of damage
      control including appropriate resuscitation, hemorrhage control, coagulopathy
      correction and multiple debridements and closure of the wounds in reasonable
      period of time can save the life of cases suffering from severe pelvic ring
      injury.

PMID- 23953034
TI  - Comparison of molecular breeding values based on within- and across-breed
      training in beef cattle.
AB  - BACKGROUND: Although the efficacy of genomic predictors based on within-breed
      training looks promising, it is necessary to develop and evaluate across-breed
      predictors for the technology to be fully applied in the beef industry. The
      efficacies of genomic predictors trained in one breed and utilized to predict
      genetic merit in differing breeds based on simulation studies have been reported,
      as have the efficacies of predictors trained using data from multiple breeds to
      predict the genetic merit of purebreds. However, comparable studies using beef
      cattle field data have not been reported. METHODS: Molecular breeding values for
      weaning and yearling weight were derived and evaluated using a database
      containing BovineSNP50 genotypes for 7294 animals from 13 breeds in the training
      set and 2277 animals from seven breeds (Angus, Red Angus, Hereford, Charolais,
      Gelbvieh, Limousin, and Simmental) in the evaluation set. Six single-breed and
      four across-breed genomic predictors were trained using pooled data from purebred
      animals. Molecular breeding values were evaluated using field data, including
      genotypes for 2227 animals and phenotypic records of animals born in 2008 or
      later. Accuracies of molecular breeding values were estimated based on the
      genetic correlation between the molecular breeding value and trait phenotype.
      RESULTS: With one exception, the estimated genetic correlations of within-breed
      molecular breeding values with trait phenotype were greater than 0.28 when
      evaluated in the breed used for training. Most estimated genetic correlations for
      the across-breed trained molecular breeding values were moderate (> 0.30). When
      molecular breeding values were evaluated in breeds that were not in the training
      set, estimated genetic correlations clustered around zero. CONCLUSIONS: Even for
      closely related breeds, within- or across-breed trained molecular breeding values
      have limited prediction accuracy for breeds that were not in the training set.
      For breeds in the training set, across- and within-breed trained molecular
      breeding values had similar accuracies. The benefit of adding data from other
      breeds to a within-breed training population is the ability to produce molecular
      breeding values that are more robust across breeds and these can be utilized
      until enough training data has been accumulated to allow for a within-breed
      training set.

PMID- 23953035
TI  - A prospective video-based observational and analytical approach to evaluate
      management during brain tumour surgery at a university hospital.
AB  - The operating room (OR) is a high-risk complex setting, where patient safety
      relies on the coordinated efforts of multiple team members. However, little
      attention has been paid to evaluating the strategies employed by OR practitioners
      to prevent and correct incidents that inevitably occur during surgery. Therefore,
      we were prompted to investigate human factor (HF) engineering methods that have
      been used in an innovative way in order to systematically observe and analyze the
      management of incidents in the neurosurgical OR of a French university hospital.
      A technical case report illustrates our approach that associates the following
      procedures: the recording of OR team member activities and behaviour by video
      cameras and direct observation of a HF researcher, with the description and the
      explicit demonstration of safety related procedures in self- and cross
      confrontation interviews of OR team members. This technical report emphasizes
      complementary aspects of clinical performance related to safety skills. Moreover,
      individual and team performances rely on complementary abilities that associate
      practical knowledge, skills, and attitudes, which are engaged at various degrees
      to prevent and manage incidents. This report also enlightens new quality
      improvement opportunities as well as further objectives for future studies. 

PMID- 23953036
TI  - The incidence of retained guidewires after central venous catheterization in a
      tertiary care center.

PMID- 23953037
TI  - Is S100B protein level really not an indicator of brain damage due to carbon
      monoxide poisoning in children?

PMID- 23953038
TI  - Specificity profile of venlafaxine and sertraline in major depression:
      metaregression of double-blind, randomized clinical trials.
AB  - Despite the well-known efficacy of selective serotonin reuptake inhibitors
      (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in the treatment
      of major depressive disorder, there is a lack of indications for each drug in
      different groups of patients. The aim of this study is to investigate the
      possible role of clinical sociodemographic factors as moderators of clinical
      response to venlafaxine (SNRI) and sertraline (SSRI). Research was performed on
      Medline and EMBASE for randomized control trials in English focused on sertraline
      and venlafaxine in the treatment of major depressive disorder and 59 studies were
      included. Clinical efficacy of each treatment was assessed on the basis of
      Hamilton Depressive Rating Scale and Montgomery-Asberg Depression Rating Scale. A
      metaregression analysis was performed to evaluate the role of clinical and
      sociodemographic factors as moderators of outcome, calculating the effect of each
      variable with the random-effects method. Gender, ethnicity and duration of
      depressive episode could have a role in prediction of clinical response to both
      antidepressants. Venlafaxine seems to have better effects in females and in
      Caucasian patients. Sertraline seems to be more efficacious in the treatment of
      females. Both drugs were more efficacious in patients who suffered a shorter
      episode of illness. Our results could represent an interesting point of view in
      the perspective of choosing the most suitable therapy based on clinical and
      social features for each patient. Metaregression is a retrospective analysis,
      based on the cumulative results of previous studies, so the lack of original data
      could represent the main limitation in this report and in the interpretation of
      the results obtained. 

PMID- 23953039
TI  - [Long-term results of radiofrequency catheter ablation of long-lasting persistent
      atrial fibrillation: five years of follow-up].
AB  - AIM: To evaluate long-term results of radiofrequency catheter ablation (RFA) vs.
      rate-control strategy in patients with long-lasting persistent atrial
      fibrillation (AF) METHODS: We assessed 5-years results in 66 patients (53.3+/
      12.3 years old, 8 women) with long-lasting persistent AF who underwent RFA
      (ablation group), as well as in age-gender-AF duration-matched patients who were
      treated with rate-control strategy (rate-control group).The ablation strategy
      consisted of wide-area circumferential lines around pulmonary veins, roof lines
      and extensive RFA of the left atrial substrate modification using a three
      dimensional mapping system. Incidence of sinus rhythm (SR) maintenance, death,
      stroke, myocardial infarction (MI), worsening of heart failure (NYHA) were
      evaluated after 5 years of follow-up. RESULTS: After 5 years of follow up SR was
      present in 38 (56%) of 42 who were under follow up patients of ablation group and
      all patients had AF in rate-control group (95% CI 0.02247-0.3598; p=0.0001).
      Seventeen (27%) patients of ablation group continued to take atniarrhythmic
      drugs. 29 (44%) patients of ablation group vs. 48 (73%) patients of rate-control
      group received warfarin (95% CI 0.442-1.1; p=0.046) at five years of follow up.
      After five years of follow up the incidence of MI, stroke, worsening of heart
      failure functional class, and death in the ablation/rate-control groups were
      0%/7.5% (95% CI 0.05247-0.30898; p=0,006), 0%/9% (95% CI 0.08903-0.32561;
      p=0.001), 6%/25% (95% CI 0.147-0.894; p=0.006), and 0.02%/0%, respectively.
      CONCLUSIONS: In patients with long-lasting persistent AF ablation strategy
      results in stable SR in the majority of patients, and decreased incidence of
      cardiovascular events compared with rate-control strategy during up to 5 years of
      follow-up.

PMID- 23953040
TI  - [Genetic predictors of sick sinus node syndrome].
AB  - The article is devoted to the role of heredity in development of the sick sinus
      node syndrome (SSNS). We have examined 14 probands and 110 their relatives from
      families with idiopathic SSNS and established the role in development of
      hereditary SSNS of polymorphisms of the following genes: -2-adrenoreceptor,
      enzyme endothelial NO synthase, protein connexin 40, voltage dependent cardiac
      sodium channels, cardiac myosin heavy chains. We also revealed associations of
      clinical variants of idiopathic SSNS with genotypes of the studied genes. 

PMID- 23953041
TI  - [The role of matrix metalloproteinases in assessment of prognosis in patients
      with ST-elevation myocardial infarction during hospital stay].
AB  - Aim of the study was to investigate role of matrix metalloproteinases (MMP) in
      assessment of prognosis of repetitive cardiovascular events during hospital stay
      of patients with ST-elevation (STE) myocardial infarction (MI). We consecutively
      included into this study 175 patients with diagnosis of STEMI. Content of MMP-1,
      MMP-3 and MMP-9 in blood serum was measured at admission and on day 12 after
      onset of disease. Levels of all MMPs on day 12 were 1.1-1.6 times higher than on
      day 1 of MI (<0.05). Comparison of groups of patients with favorable and
      unfavorable outcome showed that patients with unfavorable outcome had higher
      median concentrations of MMP-3 and MMP-9 on day 1; this tendency was maintained
      on day 12. However these differences were significant only for MMP-9. Compared
      with patients with favorable outcome levels of this marker in patients with
      unfavorable outcome were higher by 19.4% (=0.04) on day 1 and by 48.8% (=0.03) on
      day 12. At logistic regression analysis for MMP-9 and unfavorable outcomes during
      hospital stay area under ROC-curve did not exceed 0.5. But when only inhospital
      deaths were considered 2 for MMP-9 (day 1) was 14.3 (<0.0001) while area under
      ROC-curve was 0.72 (0.64; 0.78; =0.02). Thus in patients with STEMI high
      concentrations of MMP-9 on day 1 of STEMI can come forward as independent marker
      of unfavorable outcome during hospital stay. 

PMID- 23953042
TI  - [Combined therapy of arterial hypertension with the fixed combination of
      perindopril arginine / amlodipine in real clinical practice: the organization and
      the main results of the program CONSTANTA].

PMID- 23953043
TI  - [Cardiorespiratory abnormalities and cerebral oxygen supply in chronic
      thromboembolic pulmonary hypertension].
AB  - Aim of the study was assessment of severity of cardiorespiratory abnormalities
      and cerebral oxygen supply in patients with chronic thromboembolic pulmonary
      hypertension (CTEPH). We examined 56 patients with diagnosis of chronic pulmonary
      thromboembolism and duration of the disease 3 (1.5-4.1) years. According to data
      of pulmonary angiography pulmonary artery pressure was 78 (58-92) mm Hg,
      pulmonary vascular resistance - 618 (450-935) dyne/sec/cm-5, Miller index - 25
      (22-27). Further investigation revealed changes of anatomo-functional parameters
      of the heart and parameters of pulmonary ventilation. These changes were
      associated with insufficient oxygen supply to the brain and lowering of tolerance
      to hypoxia. Results of this study should be taken into consideration when brain
      protective measures are provided during surgical treatment of CTEPH. 

PMID- 23953044
TI  - [Prognostic role of C-reactive protein in progression of atherosclerosis in a
      year after coronary bypass surgery].
AB  - Aim of the study was to assess prognostic role of high sensitivity C-reactive
      protein (CRP) in progression of atherosclerosis in patients with ischemic heart
      disease (IHD) in a year after coronary artery bypass grafting (CABG). We examined
      49 patients with stable IHD subjected to elective CABG (45 with and 4 without
      without cardiopulmonary bypass). In a year after surgery patients were divided
      into 2 groups: with (group 1, n=18, 36.7%) and without (group 2, n=31, 63.3%)
      progression of atherosclerosis of any localization. Contribution of various
      clinical and instrumental factors, type of intervention, CRP level before and in
      1 year after surgery was analyzed. Before CABS CRP level was 3 times higher in
      group 1 compared with group 2 (=0.03). Increase of intima-media thickness was
      registered in a year after CABS in both groups, but it was significant only in
      patients with atherosclerosis progression (=0.04). Other clinical factors, gender
      characteristics of groups, type of intervention exerted no significant influence
      on progression of systemic atherosclerosis. 

PMID- 23953045
TI  - [Inhospital thrombolism of right cardiac chambers].
AB  - Veins of lower extremities are classic sources of pulmonary artery
      thromboembolism (PATE). But one should not underestimate presence of thrombi in
      other potential sources - veins of small pelvis, superior vena cava, and chambers
      of the heart. We analyzed 652 case histories and autopsy data of patients in whom
      PATE had been revealed at pathological anatomical investigation and selected 157
      cases in which right heart chambers were sources of emboli (right atrium in 83.5%
      and right ventricle - in 13.7% of cases). According to autopsy data average mass
      of the heart was 512.5+/-36.1 g. In most patients it exceeded norm. Thrombi in
      both right and left cardiac chambers were found in 52.3% of cases. Eighty three
      patients had history of myocardial infarction or were treated for MI during last
      hospitalization; 52.3% of patients had atrial fibrillation. After detailed study
      of all anamnestic, clinical, instrumental, and pathologic-anatomic data we
      selected 69 factors which according to contemporary views could facilitate
      formation of thrombus in the right cardiac chambers. Using these factors and
      method of logistic regression we created a mathematical model for assessment of
      probability of the presence of thrombi in right cardiac chambers. 

PMID- 23953046
TI  - [Osteoporosis and arterial stiffness: study of 103 women with mild to moderate
      risk of cardiovascular disease].
AB  - OBJECTIVE: to evaluate the relationship between arterial stiffness and bone
      metabolism in women with mild to moderate risk of cardiovascular disease (CVD).
      METHODS: In 103 postmenopausal women (mean age 57.0 years, 95% CI 50.0-64.0) with
      mild to moderate risk of CVD (SCORE<5), no more than mild hypertension, normal
      function of thyroid gland, without coronary artery disease, diabetes mellitus and
      secondary causes of osteoporosis pulse wave velocity between carotid and femoral
      sites (cfPWV, by applanation tonometry) and ankle and brachial sites (baPWV, by
      volume sphygmography) as well as bone mineral density at lumbar spine and femoral
      neck (by dual-energy X-ray absorptiometry) and blood serum levels of markers of
      bone turnover (total procollagen type I amino-terminal propeptide (PINP),
      osteocalcin, collagen type 1 cross-linked C-telopeptide (-CTX) by
      electrochemilumininescence immunoassay) were assessed. RESULTS: Compared with
      patients with normal mineral bone density (BMD) (n=27), patients with
      osteoporosis (n=31) had higher cfPWV and baPWV values (p<0.05). Patients with
      osteopenia did not differ from other groups (p>0.05). In osteoporosis group there
      were greater years since menopause, less body mass index than in normal BMD (in
      all cases p<0.05; ns between osteoporosis and osteopenia groups). Between all
      three groups there were no significant differences in age, smoking status, visit
      blood pressure, lipid levels and medication. CfPWV and baPWV values significantly
      positively correlated with age, systolic arterial pressure, years since
      menopause, procollagen type I N propeptide (all p<0.05), and significantly
      negatively correlated with BMD at hip neck (all p<0.05). Relationship between
      cfPWV and BMD at lumbar spine did not reach significant value (r=-0.18, p=0.068).
      No relationship was found between parameters of arterial stiffness and CTX and
      osteocalcin (all p>0.05). In the multivariate analysis cfPWV was significantly
      and independently associated with systolic blood pressure (=1.03, 95% CI 1.00
      1.06, p=0.03) and BMD at hip neck (=0.01, 95% CI 0.001-0.07, p=0.003).
      CONCLUSION: Revealed association between arterial stiffness and bone metabolism
      may probably explain general mechanisms of arterial and bone damage in
      postmenopausal women with mild to moderate risk of cardiovascular disease.

PMID- 23953047
TI  - [Results of large clinical studies presented at the European Society of
      Cardiology Congress 2012].
AB  - The article contains short characteristics of 6 novel European guidelines on the
      treatment of cardiovascular diseases and accounts of main scientific sessions
      (Hot Line, Clinical Trial and Registry Update) of the European Society of
      Cardiology Congress 2012. 

PMID- 23953048
TI  - [Hypertensive crisis: pathogenesis, clinic, treatment].
AB  - Contemporary data on mechanisms of development, types, and clinical picture of
      hypertensive crisis (HC) are presented. Algorithms of rational therapy of
      uncomplicated and complicated HC are considered. Appropriateness of the use in HC
      of antihypertensive drugs with multifactorial action is stressed. These drugs
      include urapidil - an antihypertensive agent with complex mechanism of action.
      Blocking mainly the postsynaptic 1-adrenoreceptors urapidil attenuates
      vasoconstrictor effect of catecholamines and decreases total peripheral
      resistance. Stimulation of 5HT1-receptors of medullary vasculomotor center
      promotes lowering of elevated vascular tone and prevents development of reflex
      tachycardia. 

PMID- 23953049
TI  - [Clinical significance of filiform structures (Lambls excrescences) on cusps of
      cardiac valves].
AB  - This literature review is devoted to clinical significance of filiform structures
      (Lambls excrescences) which can be revealed on cusps of cardiac valves by
      transesophageal echocardiography. The review contains analysis of frequency of
      detection of these structures at pathomorphological investigation and
      transesophageal echocardiography as well as consideration of their histological
      construction and mechanisms of formation. Special emphasis is made on mechanisms
      of related embolic complications and data on association of Lambls excrescences
      with strokes. Differential diagnosis of these structures and other pathological
      elements on heart valves is also presented. 

PMID- 23953050
TI  - [Chronic heart failure and osteoporosis].
AB  - Osteoporosis (OP) and chronic heart failure (CHF) are chronic noninfection
      diseases which are characterized not only by high prevalence but also by
      development of severe complications such as fractures in OP and decompensation in
      CHF. These complications lead to loss of functional, social activity and
      independent way of life, worsening of quality of life, hospitalizations, and
      premature death of a patient. During many years OP and CHF have been looked upon
      as independent diseases but according to recent data risk factors of their
      development and progression are common. In this article we pay special attention
      to mechanisms of development of CHF and OP, their risk factors, instrumental and
      laboratory diagnosis of OP, and problems of its treatment. 

PMID- 23953051
TI  - [Clinical cfficacy of calcium channel blockers slow the third generation of
      lercanidipine in the treatment of patients with arterial hypertension].
AB  - The review describes the classification, mechanisms of action, the effects of
      calcium channel blockers slow and the clinical benefits of dihydropyridine
      calcium antagonists, the third generation. Presented modern aspects of clinical
      pharmacology and research results on the efficacy, safety and organoprotective
      lercanidipine. 

PMID- 23953052
TI  - [Practical value of omega-3 polyunsaturated fatty acids for prevention of sudden
      cardiac death].

PMID- 23953053
TI  - The metabolic modulator trimetazidine triggers autophagy and counteracts stress
      induced atrophy in skeletal muscle myotubes.
AB  - It has recently been demonstrated that trimetazidine (TMZ), an anti-ischemic
      antianginal agent, is also able to improve exercise performance in patients with
      peripheral arterial disease. TMZ is a metabolic modulator, and the mechanisms
      underlying its cytoprotective anti-ischemic activity could be ascribed, at least
      in cardiomyocytes, to optimization of metabolism. However, regarding the
      cytoprotection exerted by TMZ on skeletal muscle and allowing the improvement of
      exercise performance, no information is yet available. In the present study, we
      investigated in detail the protective effects of this drug on in vitro skeletal
      muscle models of atrophy. Experiments carried out with murine C2C12 myotubes
      treated with TMZ revealed that this drug could efficiently counteract the
      cytopathic effects induced by the proinflammatory cytokine tumor necrosis factor
      alpha and by the withdrawal of growth factors. Indeed, TMZ significantly
      counteracted the reduction in myotube size induced by these treatments. TMZ also
      increased myosin heavy chain expression and induced hypertrophy in C2C12
      myotubes, both effects strongly suggesting a role of TMZ in counteracting atrophy
      in vitro. In particular, we found that TMZ was able to activate the
      phosphoinositide 3-kinase-Akt-mammalian target of rapamycin 2 pathway and to
      reduce the stress-induced transcriptional upregulation of atrogin-1, muscle ring
      finger protein 1, and myostatin, all of which are key molecules involved in
      muscle wasting. Moreover, this is the first demonstration that TMZ induces
      autophagy, a key mechanism involved in muscle mass regulation. On the basis of
      these results, it can be hypothesized that the improvement in exercise
      performance previously observed in patients could be ascribed to a cytoprotective
      mechanism exerted by TMZ on skeletal muscle integrity.

PMID- 23953054
TI  - Tundra ecosystems observed to be CO2 sources due to differential amplification of
      the carbon cycle.
AB  - Are tundra ecosystems currently a carbon source or sink? What is the future
      trajectory of tundra carbon fluxes in response to climate change? These questions
      are of global importance because of the vast quantities of organic carbon stored
      in permafrost soils. In this meta-analysis, we compile 40 years of CO2 flux
      observations from 54 studies spanning 32 sites across northern high latitudes.
      Using time-series analysis, we investigated if seasonal or annual CO2 fluxes have
      changed over time, and whether spatial differences in mean annual temperature
      could help explain temporal changes in CO2 flux. Growing season net CO2 uptake
      has definitely increased since the 1990s; the data also suggest (albeit less
      definitively) an increase in winter CO2 emissions, especially in the last decade.
      In spite of the uncertainty in the winter trend, we estimate that tundra sites
      were annual CO2 sources from the mid-1980s until the 2000s, and data from the
      last 7 years show that tundra continue to emit CO2 annually. CO2 emissions exceed
      CO2 uptake across the range of temperatures that occur in the tundra biome. Taken
      together, these data suggest that despite increases in growing season uptake,
      tundra ecosystems are currently CO2 sources on an annual basis. 

PMID- 23953055
TI  - Obesity increases the incidence of distant metastases in oestrogen receptor
      negative human epidermal growth factor receptor 2-positive breast cancer
      patients.
AB  - BACKGROUND: Obesity is a major negative determinant of breast cancer outcome.
      However, there are contrasting data on the differential impact of obesity on
      specific breast cancer subtypes. In particular, very little is known on human
      epidermal growth factor receptor 2-positive (HER2+) tumours. PATIENTS AND
      METHODS: We assessed the prognostic role of increased body mass index (BMI) on a
      consecutive series of non-metastatic HER2+ patients treated at our institution
      before the introduction of adjuvant Trastuzumab. We separately analysed oestrogen
      receptor-positive (ER+) and -negative (ER-) HER2+ cases. RESULTS: In ER-/HER2+
      tumours we observed a significantly worse overall survival (Hazard ratio (HR)
      1.79, p-value 0.041) and cumulative incidence of distant metastases (HR 2.03, p
      value 0.019) in obese (BMI>30) versus normal/underweight (BMI<25) patients. Local
      relapses appeared to be non-significantly reduced in obese patients, masking the
      overall effect on disease-free survival. Outcome in ER+ tumours, instead, was not
      significantly different between BMI groups. CONCLUSIONS: Obesity significantly
      correlates with worse overall survival and cumulative incidence of distant
      metastases in ER-/HER2 positive breast cancer. Differences in the biology of
      breast tumours may determine individual susceptibility to obesity. The biology of
      the underlying tumour should be taken into account in the design of dietary
      intervention trials in breast cancer.

PMID- 23953056
TI  - A phase two randomised trial of neratinib monotherapy versus lapatinib plus
      capecitabine combination therapy in patients with HER2+ advanced breast cancer.
AB  - BACKGROUND: The safety and efficacy of neratinib monotherapy were compared with
      that of lapatinib plus capecitabine in patients with human epidermal growth
      factor receptor-2-positive (HER2+), locally advanced/metastatic breast cancer and
      prior trastuzumab treatment. METHODS: Patients received neratinib 240 mg/d
      continuously (n=117) or lapatinib 1250 mg/d continuously plus capecitabine 2000
      mg/m(2) per day on days 1-14 of each 21-d cycle (n=116). The primary aim was to
      demonstrate non-inferiority of neratinib for progression-free survival (PFS).
      FINDINGS: The non-inferiority of neratinib was not demonstrated when compared
      with lapatinib plus capecitabine (hazard ratio, 1.19; 95% confidence interval,
      0.89-1.60; non-inferiority margin, 1.15). Median PFS for neratinib was 4.5 months
      versus 6.8 months for lapatinib plus capecitabine and median overall survival was
      19.7 months versus 23.6 months. Objective response rate (neratinib, 29% versus
      lapatinib plus capecitabine, 41%; P=0.067) and clinical benefit rate (44% versus
      64%; P=0.003) were lower for the neratinib arm but consistent with previously
      reported results. In both treatment arms, diarrhoea was the most frequently
      reported treatment-related adverse event of any grade (neratinib, 85% versus
      lapatinib plus capecitabine, 68%; P=0.002) and of grade 3/4 (28% versus 10%;
      P<0.001), but was typically managed with concomitant anti-diarrhoeal medication
      and/or study treatment modification. Importantly, neratinib had no significant
      skin toxicity. INTERPRETATION: The results are considered as inconclusive since
      neither inferiority nor non-inferiority of treatment with neratinib versus
      lapatinib plus capecitabine could be demonstrated. The study confirmed relevant
      single-agent clinical activity and acceptable overall tolerability of neratinib
      in patients with recurrent HER2+ advanced breast cancer.

PMID- 23953057
TI  - Activation of interleukin-6/signal transducer and activator of transcription 3 by
      human papillomavirus early proteins 6 induces fibroblast senescence to promote
      cervical tumourigenesis through autocrine and paracrine pathways in tumour
      microenvironment.
AB  - Although it is reported that interleukin (IL)-6/signal transducer and activator
      of transcription 3 (STAT3) is activated by human papillomavirus (HPV) infection
      in cervical cancer cells, little is known about the role of IL-6/STAT3 in tumour
      microenvironment during development of the disease. In this study, we found that
      cancer-associated fibroblasts (CAF) but not normal fibroblasts (NF) secrete high
      level of IL-6 with activated STAT3 and appear senescent at early passages in
      culture or in cervical cancer tissues infected with high-risk HPV, and that
      treatment of NF with recombinant IL-6 or CAF conditioned medium (CM) induces
      activation of STAT3 and cellular senescence. IL-6 and STAT3 are either
      upregulated or activated in Siha and Hela cells infected with HPV 16 or 18, but
      not in C33A and ME180 cells without HPV 16 or 18 infection. Overexpression of HPV
      early proteins 6 (E6) activates STAT3, increases IL-6 expression and tumour
      burden in C33A and ME180 cells, while silencing of HPV E6 by specific shRNA
      reduces STAT3 activation, IL-6 expression, and tumour formation in Siha and HeLa
      cells, so does silencing of STAT3 by specific shRNA in HeLa and C33A/E6 cells.
      The tumour growth of cervical cancer cells reconstituted with CAF or NF is
      largely affected by inhibition of fibroblast senescence with STAT3 inhibitor or
      with IL-6 antibody treatment. Thus, we have uncovered a mechanism that fibroblast
      senescence promotes cervical cancer development through high-risk HPV E6
      activated IL-6/STAT3 signalling in tumour microenvironment. 

PMID- 23953058
TI  - Sex and Eimeria: a molecular perspective.
AB  - Eimeria is a common genus of apicomplexan parasites that infect diverse
      vertebrates, most notably poultry, causing serious disease and economic loss.
      Like all apicomplexans, eimerians have a complex life cycle characterized by
      asexual divisions that amplify the parasite population in preparation for sexual
      reproduction. This can be divided into three events: gametocytogenesis, producing
      gametocytes from merozoites; gametogenesis, producing microgametes and
      macrogametes from gametocytes; and fertilization of macrogametes by microgametes,
      producing diploid zygotes with ensuing meiosis completing the sexual phase.
      Sexual development in Eimeria depends on the differential expression of stage
      specific genes, rather than presence or absence of sex chromosomes. Thus, it
      involves the generation of specific structures and, implicitly, storage of
      proteins and regulation of protein expression in macrogametes, in preparation for
      fertilization. In Eimeria, the formation of a unique, resilient structure, the
      oocyst wall, is essential for completion of the sexual phase and parasite
      transmission. In this review, we piece together the molecular events that
      underpin sexual reproduction in Eimeria and use additional details from analogous
      events in Plasmodium to fill current knowledge gaps. The mechanisms governing
      sexual stage formation and subsequent fertilization may represent targets for
      counteracting parasite transmission.

PMID- 23953060
TI  - Monkeys, apes, imitation and mirror neurons.

PMID- 23953059
TI  - Electromyographic analysis of reverse total shoulder arthroplasties.
AB  - BACKGROUND: Understanding how reverse total shoulder arthroplasty (RTSA) affects
      muscle activation may help refine it. This study evaluated deltoid and upper
      trapezius activity during shoulder abduction, flexion, and external rotation in
      RTSA recipients. METHODS: Fifty individuals were recruited for this study: 33
      were >=6 months postunilateral RSTA, and 17 comprised our control group. Control
      individuals easily performed all functional tasks and had no history of shoulder
      pathology or pain. RTSA participants were divided into 3 groups according to
      implant design. Participants performed weighted and unweighted abduction in the
      coronal plane, forward flexion in the sagittal plane, and unweighted external
      rotation. Electromyography activation of the anterior, lateral, and posterior
      aspects of the deltoid and the upper trapezius muscles was recorded bilaterally.
      Motion capture using passive reflective markers quantified 3-dimensional motions
      of both shoulders. RESULTS: During abduction and flexion, deltoid and upper
      trapezius activity was significantly increased in RTSA shoulders. Posterior
      deltoid activation was highest in shoulders with the medial glenosphere/lateral
      humerus implant. Medial glenosphere/medial humerus shoulders were most similar to
      the control group's anterior, lateral, and posterior deltoid muscle activation
      during weighted flexion. CONCLUSIONS: RTSA increases muscle activation compared
      with normal shoulders. RTSA often restores stability and motion but not normal
      deltoid or upper trapezius activation. Increased muscle activation in shoulders
      with RTSA suggests less efficiency. RTSAs with lateral or medial glenosphere
      centers of rotation had mostly similar muscle activation. Average posterior
      deltoid activation did not exceed 20% of maximal voluntary isometric contraction
      for any group during unweighted external rotation, and differences between groups
      were <5% maximal voluntary isometric contraction.

PMID- 23953061
TI  - Mental reliving and the self.

PMID- 23953062
TI  - Observing object lifting errors modulates cortico-spinal excitability and
      improves object lifting performance.
AB  - Observing the actions of others has been shown to modulate cortico-spinal
      excitability and affect behaviour. However, the sensorimotor consequences of
      observing errors are not well understood. Here, participants watched actors lift
      identically weighted large and small cubes which typically elicit expectation
      based fingertip force errors. One group of participants observed the standard
      overestimation and underestimation-style errors that characterise early lifts
      with these cubes (Error video--EV). Another group watched the same actors
      performing the well-adapted error-free lifts that characterise later, well
      practiced lifts with these cubes (No error video--NEV). We then examined actual
      object lifting performance in the subjects who watched the EV and NEV. Despite
      having similar cognitive expectations and perceptions of heaviness, the group
      that watched novice lifters making errors themselves made fewer overestimation
      style errors than those who watched the expert lifts. To determine how the
      observation of errors alters cortico-spinal excitability, we measured motor
      evoked potentials in separate group of participants while they passively observed
      these EV and NEV. Here, we noted a novel size-based modulation of cortico-spinal
      excitability when observing the expert lifts, which was eradicated when watching
      errors. Together, these findings suggest that individuals' sensorimotor systems
      are sensitive to the subtle visual differences between observing novice and
      expert performance.

PMID- 23953063
TI  - Routine exercise ameliorates the metabolic side-effects of treatment with the
      atypical antipsychotic drug olanzapine in rats.
AB  - Second generation antipsychotic (SGA) drugs are effective treatments for
      psychosis. Common side-effects of SGAs include metabolic dysregulation and risk
      of cardiometabolic disorders. Metabolic side-effects, including glucose
      intolerance, can be accurately modelled in rodents. The benefits of interventions
      used for treating metabolic side-effects of SGAs are mostly unknown. In a 9 wk
      longitudinal study, female rats were given daily olanzapine (10 mg/kg s.c.) or
      vehicle. Animals were either sedentary or allowed 1 or 3 h daily access to a
      running wheel, with total wheel revolutions electronically quantified to reflect
      exercise intensity. Glucose tolerance tests were performed once weekly to measure
      glycemic control. Drug levels were measured at week 4. At week 9, abdominal fat
      and skeletal muscle levels of Glucose Transporter 4 (GLUT4) were measured.
      Exercise intensity progressively increased over time in all groups given access
      to running wheels; however, rats treated with olanzapine consistently exercised
      less than those given the vehicle. Olanzapine caused acute and persistent glucose
      intolerance throughout the study, which was markedly, though incompletely,
      ameliorated by exercise. Exercise did not affect glycemic regulation in vehicle
      treated rats. Olanzapine-treated rats showed greater central adiposity. Levels of
      GLUT4 in skeletal muscle were higher in both groups of exercising than in
      sedentary rats, and GLUT4 values were negatively correlated with glucose
      intolerance. Routine exercise reduced olanzapine-induced glucose intolerance and
      increased skeletal muscle levels of GLUT 4, the insulin-responsive transporter
      that mediates glucose uptake into cells. The current animal model is suitable for
      evaluating physiological pathways involved with glucose intolerance. 

PMID- 23953064
TI  - QTL mapping of egg albumen quality in egg layers.
AB  - BACKGROUND: A fresh, good quality egg has a firm and gelatinous albumen that
      anchors the yolk and restricts growth of microbiological pathogens. As the egg
      ages, the gel-like structure collapses, resulting in thin and runny albumen.
      Occasionally thin albumen is found in a fresh egg, giving the impression of a low
      quality product. A mapping population consisting of 1599 F2 hens from a cross
      between White Rock and Rhode Island Red lines was set up, to identify loci
      controlling albumen quality. The phenotype for albumen quality was evaluated by
      albumen height and in Haugh units (HU) measured on three consecutive eggs from
      each F2 hen at the age of 40 weeks. For the fine-mapping analysis, albumen height
      and HU were used simultaneously to eliminate contribution of the egg size to the
      phenotype. RESULTS: Linkage analysis in a small population of seven half-sib
      families (668 F2) with 162 microsatellite markers spread across 27 chromosomes
      revealed two genome-wide significant regions with additive effects for HU on
      chromosomes 7 and Z. In addition, two putative genome-wide quantitative trait
      loci (QTL) regions were identified on chromosomes 4 and 26. The QTL effects
      ranged from 2 to 4% of the phenotypic variance. The genome-wide significant QTL
      regions on chromosomes 7 and Z were selected for fine-mapping in the full set
      composed of 16 half-sib families. In addition, their existence was confirmed by
      an association analysis in an independent commercial Hy-Line pure line.
      CONCLUSIONS: We identified four chicken genomic regions that affect albumen
      quality. Our results also suggest that genes that affect albumen quality act both
      directly and indirectly through several different mechanisms. For instance, the
      QTL regions on both fine-mapped chromosomes 7 and Z overlapped with a previously
      reported QTL for eggshell quality, indicating that eggshell membranes may play a
      role in albumen quality.

PMID- 23953065
TI  - MOLE 2.0: advanced approach for analysis of biomacromolecular channels.
AB  - BACKGROUND: Channels and pores in biomacromolecules (proteins, nucleic acids and
      their complexes) play significant biological roles, e.g., in molecular
      recognition and enzyme substrate specificity. RESULTS: We present an advanced
      software tool entitled MOLE 2.0, which has been designed to analyze molecular
      channels and pores. Benchmark tests against other available software tools showed
      that MOLE 2.0 is by comparison quicker, more robust and more versatile. As a new
      feature, MOLE 2.0 estimates physicochemical properties of the identified
      channels, i.e., hydropathy, hydrophobicity, polarity, charge, and mutability. We
      also assessed the variability in physicochemical properties of eighty X-ray
      structures of two members of the cytochrome P450 superfamily. CONCLUSION:
      Estimated physicochemical properties of the identified channels in the selected
      biomacromolecules corresponded well with the known functions of the respective
      channels. Thus, the predicted physicochemical properties may provide useful
      information about the potential functions of identified channels. The MOLE 2.0
      software is available at http://mole.chemi.muni.cz.

PMID- 23953066
TI  - Effect of antithyroid antibodies on ICSI outcome in antiphospholipid antibody
      negative euthyroid women.
AB  - Antithyroid antibodies (ATA) are found in 5-15% of women at reproductive age and
      are not necessarily accompanied with thyroid dysfunction. ATA are associated with
      adverse effects such as spontaneous miscarriage, recurrent miscarriages, preterm
      delivery and maternal post-partum thyroiditis in women with normal thyroid
      hormone concentrations. The role of ATA on the outcome of IVF cycles remains to
      be investigated. This study evaluated the impact of ATA on the outcome of
      intracytoplasmic sperm injection (ICSI)-embryo transfer cycles in euthyroid
      women. A total of 253 women undergoing ICSI-embryo transfer cycles were
      prospectively enrolled in this study. Women positive for at least one of the
      thyroid antibodies, with normal thyroid-stimulating hormone (TSH) and free T4
      concentrations and negative for anticardiolipin antibodies and lupus
      anticoagulant were included. ICSI was performed for fertilization in all cycles.
      Of 253 women, 219 were ATA negative and 34 ATA positive. Implantation rates
      (19.1% versus 18.4%), miscarriage rates (9.0% versus 8.3%) and ongoing pregnancy
      rates (37.0% versus 32.4%) did not differ significantly between the ATA-positive
      group and the ATA-negative group, respectively. The presence of antithyroid
      antibodies in euthyroid and antiphospholipid antibody-negative women was not
      found to significantly affect the outcome of ICSI-embryo transfer cycles.
      Antithyroid antibodies (ATA) can interact with thyroid hormone receptors located
      on the human oocyte and impair the chance of fertilization and healthy pregnancy.
      They are found in 5-15% of women at reproductive age and are not necessarily
      accompanied with thyroid dysfunction. ATA have been reported to be associated
      with adverse effects such as spontaneous miscarriage, recurrent miscarriages,
      preterm delivery and maternal post-partum thyroiditis in women with normal
      thyroid hormone concentrations. The role of ATA on the outcome of IVF cycles
      remains to be investigated. The objective of our study was to evaluate the impact
      of ATA on the outcome of intracytoplasmic sperm injection (ICSI)-embryo transfer
      cycles in euthyroid women. A total of 253 women undergoing ICSI-embryo transfer
      cycles were prospectively enrolled in this study. Women with at least one of the
      thyroid antibodies positive and normal TSH and free T4 concentrations were
      included in the study. Since other immunological disorders might affect the
      results, antiphospholipid antibodies (APA), which are the markers of
      antiphospholipid antibody syndrome, were also screened in all women prior to
      study. Women with positive for APA were excluded in the final analysis. Of 253
      women, 219 (86.6%) were ATA negative and 34 (13.4%) ATA positive. Implantation
      rates (19.1% versus 18.4%), biochemical pregnancy rates (9.2% versus 14.3%),
      miscarriage rates (9.0% versus 8.3%) and ongoing pregnancy rates (37.0% versus
      32.4%) did not differ significantly between the ATA-positive group and the ATA
      negative group, respectively. In conclusion, presence of antithyroid antibodies
      in euthyroid and antiphospholipid antibody-negative women does not affect the
      outcome of ICSI-embryo transfer cycles. 

PMID- 23953068
TI  - A survey of 1700 women who formed their families using donor spermatozoa.
AB  - This paper reports the results of an online survey of 1700 recipients of donor
      spermatozoa conducted by the Donor Sibling Registry, aiming to understand the
      perspectives of respondents who had used donor spermatozoa. The survey examined:
      choice of sperm bank and donor; reporting of births and genetic disorders;
      disclosure; contact with donor and half-siblings; regulation of sperm donor
      activity and genetic testing; and access to medical information. The respondents
      formed three groups: single women; women in a same-sex relationship; and women in
      a heterosexual relationship. Some differences between the three cohorts were
      observed: preinsemination counselling; acceptance of donors without medical
      records or with chronic or late-onset diseases; awareness of choice of bank and
      type of donor; and views on the right of offspring to know their genetic origins.
      However, important areas of common ground were identified: the wish by those who
      had used an anonymous donor that they had used an open-identity donor; support
      for, and willingness to pay for, comprehensive genetic testing of donors; and
      desire for access to their donor's family health information. The implications of
      these results for policies concerning the use and management of donor spermatozoa
      will be discussed. This paper reports the results of a survey of 1700 women who
      used donor spermatozoa to conceive a child. The survey considers their views on
      the following areas: choice of sperm bank and donor; reporting of births and
      genetic disorders; disclosure; contact with donor and half-siblings; regulation
      of sperm donor activity and genetic testing; and access to medical information.
      This was an online survey was designed and conducted by the Donor Sibling
      Registry (DSR), a US-based non-profit organization that supports donor sperm
      recipients, donors and donor-conceived people. The survey aimed to understand the
      experiences, perspectives and concerns of women who had used donor spermatozoa.
      The respondents formed three groups: single women; women in a same sex
      relationship; and women in a heterosexual relationship. Some differences between
      the three groups were observed: preinsemination counselling; acceptance of donors
      without medical records or with chronic or late-onset diseases; awareness of
      choice of bank and type of donor; and the right of offspring to know their
      genetic origins. However, despite these differences, important areas of common
      ground were identified: the wish by those who had used an anonymous donor that
      they had used an open-identity donor; support for, and a willingness to pay for,
      comprehensive genetic testing of donors; and desire for access to their donor's
      family health information. The implications of these results for policies
      concerning the use and management of donor spermatozoa will be discussed. 

PMID- 23953069
TI  - Anti-Mullerian hormone versus antral follicle count for defining the starting
      dose of FSH.
AB  - This pilot study compared the efficacy and safety of two simple dosing
      algorithms, one based on anti-Mullerian Hormone (AMH) and the other on the antral
      follicle count (AFC), to determine the starting dose of recombinant FSH (rFSH)
      for ovarian stimulation in 348 women. Patients were randomized to a predefined
      AMH- or AFC-based algorithm. The proportion of cycles with the desired response
      was similar when rFSH dose was determined using AMH or AFC (35.2% versus 28.4%).
      There was a significant difference between the groups in the proportion of cycles
      with a hyperresponse (8.6% and 17.4%, but the incidence of ovarian
      hyperstimulation syndrome was similar (1.1% and 4.6%). There were no significant
      differences between two groups in outcomes, including implantation (19.3% versus
      19.0%), clinical pregnancy (38.0% versus 46.9%), multiple pregnancy (16.5% versus
      15.2%) and miscarriage (7.0% versus 8.3%). However, statistically significant
      differences in ovarian response were evident among the AMH and AFC subgroups: for
      AMH, Desired and Hypo; for AFC, Hypo and Hyper. This pilot study provides
      information for developing protocols to further validate the use of either AMH or
      AFC to guide the starting dose of rFSH in ovarian stimulation. The ideal outcome
      for couples undergoing IVF treatment is the birth of a healthy baby. One factor
      that might influence this is retrieving an adequate number of eggs, which are
      obtained using various treatment protocols. A group of drugs called
      gonadotrophins have been used for more than 20years to stimulate the ovaries to
      produce eggs. However, the dose to start treatment has not been clearly defined.
      A few studies have looked at ways to use the best gonadotrophin dose for each
      woman, but to be useful in the clinic any approach needs to be simple and easy to
      use. This study compared the effectiveness and safety of two simple approaches to
      determining the starting dose of recombinant FSH (rFSH) for ovarian stimulation
      in women undergoing IVF. One was based on the concentration of a hormone secreted
      by developing eggs (anti-Mullerian hormone; AMH) and the other on the number of
      developing follicles (antral follicle count; AFC). The number of cycles achieving
      the desired response in terms of number of eggs was similar when rFSH dose was
      guided using AMH or AFC, and the incidence of ovarian hyperstimulation syndrome
      was also similar. In addition, rates of clinical pregnancy, multiple pregnancy
      and miscarriage did not differ between the two groups. However, patients with low
      AMH concentrations or low AFC had a poor response to ovarian stimulation. This
      pilot study provides useful information from which new studies can further assess
      these approaches to personalizing treatment during IVF. 

PMID- 23953067
TI  - The human oviduct transcriptome reveals an anti-inflammatory, anti-angiogenic,
      secretory and matrix-stable environment during embryo transit.
AB  - The human oviduct serves as a conduit for spermatozoa in the peri-ovulatory phase
      and nurtures and facilitates transport of the developing embryo for nidation
      during the luteal phase. Interactions between the embryo and oviductal epithelial
      surface proteins and secreted products during embryo transit are largely
      undefined. This study investigated gene expression in the human oviduct in the
      early luteal versus follicular phases to identify candidate genes and
      biomolecular processes that may participate in maturation and transport of the
      embryo as it traverses this tissue. Oviductal RNA was hybridized to
      oligonucleotide arrays and resulting data were analysed by bioinformatic
      approaches. There were 650 genes significantly down-regulated and 683 genes
      significantly up-regulated (P<0.05) in the luteal versus follicular phase.
      Quantitative real-time PCR, immunoblot analysis and immunohistochemistry
      confirmed selected gene expression and cellular protein localization. Down
      regulated genes involved macrophage recruitment, immunomodulation and matrix
      degeneration, and up-regulated genes involved anti-inflammatory, ion transport,
      anti-angiogenic and early pregnancy recognition. The oviduct displayed some
      similarities and differences in progesterone-regulated genes compared with the
      human endometrium. Together, these data suggest a unique hormonally regulated
      environment during embryo development, maturation and transport through human
      oviduct and some conservation of progesterone signalling in tissues of common
      embryological origin. The oviduct serves as a conduit for spermatozoa in the peri
      ovulatory phase and it nurtures and facilitates transport of the developing
      embryo during the luteal phase of the menstrual cycle, although precise
      interactions between the embryo and oviductal epithelium and secreted products
      are largely undefined. Herein, we investigated gene expression in human oviduct
      to identify candidate genes and processes that may participate in maturation and
      transport of the embryo as it develops implantation competence. Total RNA from
      human ampullary oviducts in the early luteal versus follicular phases was
      isolated and hybridized to oligonucleotide arrays. The data, analysed by
      bioinformatic approaches, revealed that 650 genes were significantly down- and
      683 genes were significantly up-regulated in the luteal phase. Quantitative real
      time PCR, immunoblot analysis and immunohistochemistry confirmed selected gene
      expression and cellular protein localization. The data demonstrated down
      regulation of genes involved in macrophage recruitment, immunomodulation and
      matrix degeneration and up-regulation of ion transport and secretions, as well as
      anti-angiogenic and early pregnancy recognition. Together, these data suggest a
      unique hormonally regulated environment during embryo development, maturation and
      transport through the human oviduct and provide insight into mechanisms
      influencing acquisition of implantation competence of the human embryo during its
      passage through the oviduct en route to the uterine endometrium. 

PMID- 23953070
TI  - Discovery of potent and selective nonsteroidal indazolyl amide glucocorticoid
      receptor agonists.
AB  - Modification of a phenolic lead structure based on lessons learned from
      increasing the potency of steroidal glucocorticoid agonists lead to the discovery
      of exceptionally potent, nonsteroidal, indazole GR agonists. SAR was developed to
      achieve good selectivity against other nuclear hormone receptors with the
      ultimate goal of achieving a dissociated GR agonist as measured by human in vitro
      assays. The specific interactions by which this class of compounds inhibits GR
      was elucidated by solving an X-ray co-crystal structure. 

PMID- 23953071
TI  - Anti-CD20 monoclonal antibodies: beyond B-cells.
AB  - Anti-CD20 monoclonal antibodies (MoAbs), employed in treating CD20+ lymphomas and
      autoimmune diseases, appear to have broader functions than just eradicating
      malignant B-cells and decreasing autoantibody production. Rituximab-induced T
      cell inactivation, reported both in-vitro and in-vivo, may contribute to the
      increased risk of T-cell-dependent infections, observed in patients receiving
      this therapy. T-cell polarization into a suppressive phenotype, often observed in
      patients receiving rituximab for autoimmune disorders, was reported to be
      associated with prolonged remissions. Elimination of B-cells serving as antigen
      presenting cells, thereby causing impaired T-cell activation, could play a
      significant role in induction of these changes. Direct binding of rituximab to a
      CD20dim T-cell population, inducing its depletion, may contribute to the
      decreased T-cell activation following rituximab therapy. Further investigation of
      the complex network through which rituximab and new anti-CD20 MoAbs act, would
      advance the employment of these agents in different clinical settings.

PMID- 23953072
TI  - Preliminary investigation of the use of newborn dried blood spots for screening
      pyridoxine-dependent epilepsy by LC-MS/MS.
AB  - alpha-AASA and P6C were measured retrospectively in original newborn DBS of five
      patients with PDE using a LC-MS/MS method we developed previously. Both alpha
      AASA and P6C were elevated markedly in the three newborn DBS stored at -20
      degrees C. At room temperature, alpha-AASA and P6C in DBS appeared stable for 3
      days and then decreased by up to 70% after 14 days but remained much higher than
      control, indicating newborn screening for PDE is feasible.

PMID- 23953073
TI  - Type 2 diabetes is one of the leading causes of premature morbidity and
      mortality. Introduction.

PMID- 23953074
TI  - Options for combination therapy in type 2 diabetes: comparison of the ADA/EASD
      position statement and AACE/ACE algorithm.
AB  - Treating patients with diabetes is one of the most challenging and important
      activities a physician (primary care physician or specialist) can undertake. A
      key to successful therapy for type 2 diabetes is the insight that this condition
      is progressive and that the need for additional agents over time is normative.
      The ability to individualize therapy by patient and medication characteristics
      comes from experience and knowledge of pertinent clinical studies. However,
      guidelines from expert bodies such as the American Diabetes Association/European
      Association for the Study of Diabetes and American Association of Clinical
      Endocrinologists/American College of Endocrinology can help clinicians of all
      levels of expertise to approach therapy choices more rationally. There is unity
      across these guidelines about the role and benefits of metformin as first-line
      pharmacological treatment, probability of good efficacy, low risk of
      hypoglycemia, modest weight loss, and overall long-term data. Unfortunately, this
      unity does not extend to recommendations for subsequent pharmacological agents
      and their use in combination to intensify treatment when insulin is not (yet)
      appropriate. Across both statements, some drug classes seem more prominent, and
      looking at their benefit-risk profile, it is clear why this is the case. The most
      profound recent change in diabetes therapy has been the introduction of incretin
      therapies. Incretin therapies minimize 2 important adverse effects seen with many
      other therapies: hypoglycemia and weight gain. These agents have increased the
      range of options available for early intensification of treatment of type 2
      diabetes. In combination with more established therapies, there are more
      opportunities than ever to accommodate patient preferences while improving
      glycemic control and harnessing extraglycemic benefits of a second (or third)
      agent. 

PMID- 23953075
TI  - The early treatment of type 2 diabetes.
AB  - The growing epidemic of type 2 diabetes is one of the leading causes of premature
      morbidity and mortality worldwide, mainly due to the micro- and macrovascular
      complications associated with the disease. A growing body of evidence suggests
      that although the risk of developing complications is greater with glucose levels
      beyond the established threshold for diagnosis--increasing in parallel with
      rising hyperglycemia-individuals with glucose levels in the prediabetic range are
      already at increased risk. Early intervention, ideally as soon as abnormalities
      in glucose homeostasis are detected, is of great importance to minimize the
      burden of the disease. However, as the early stages of the disease are
      asymptomatic, diagnosing prediabetes and early overt type 2 diabetes is
      challenging. The aim of this article is to discuss these challenges, the benefits
      of early intervention--with emphasis on the prevention trials showing that
      progression to type 2 diabetes can be delayed by addressing prediabetes--and the
      existing evidence-based guidelines that have been drawn to optimize the standards
      of care at the prediabetes and overt type 2 diabetes stages.

PMID- 23953076
TI  - Initiating basal insulin therapy in type 2 diabetes: practical steps to optimize
      glycemic control.
AB  - Primary care practitioners are increasingly responsible for the management of the
      escalating numbers of patients with type 2 diabetes. The majority of these
      patients will require insulin replacement therapy as their disease progresses,
      because glycemic control is often unsustainable using oral antidiabetic drugs.
      This review explains the practicalities of initiating and optimizing basal
      insulin in clinical practice, emphasizing the need for regular glycated
      hemoglobin (A1c) monitoring to allow timely initiation of insulin when the A1c
      target is not met. The importance of patient education in overcoming barriers to
      insulin is discussed, as well as the choice of available basal insulins and the
      necessity to optimize basal insulin dosage by self-titration. The traditional
      view of insulin therapy as a last resort is challenged with the modern basal
      insulin analogues (insulin detemir and insulin glargine), which offer simple and
      effective glycemic control with a reduced risk of hypoglycemia compared with
      older insulin formulations such as neutral protamine Hagedorn. 

PMID- 23953077
TI  - Intensifying insulin therapy: what options are available to patients with type 2
      diabetes?
AB  - The progressive nature of type 2 diabetes (T2D) requires practitioners to
      periodically evaluate patients and intensify therapy when glycemic targets become
      unattainable with their current treatment regimen. Traditional first- and second
      line antidiabetic agents such as metformin and the sulfonylureas do not prevent
      the characteristic decline in beta-cell function associated with T2D; insulin
      replacement therapy can therefore quickly become a necessity in some patients.
      Basal insulin initiation provides an excellent platform to which rapid-acting
      prandial insulin doses can easily be added, potentially in a stepwise manner, as
      disease progresses. Premix insulin regimens are another effective intensification
      option following basal insulin initiation, but are most effective in insulin
      naive patients. The use of insulin in combination with modern T2D agents, such as
      the incretin-based therapies, has the potential to improve glycemic control while
      limiting insulin-associated weight gain and hypoglycemia. Further clinical data
      and approval are required before practitioners can fully endorse this novel
      approach. 

PMID- 23953078
TI  - Breaking down patient and physician barriers to optimize glycemic control in type
      2 diabetes.
AB  - Approximately half of patients with type 2 diabetes (T2D) do not achieve globally
      recognized blood glucose targets, despite the availability of a wide range of
      effective glucose-lowering therapies. Failure to maintain good glycemic control
      increases the risk of diabetes-related complications and long-term health care
      costs. Patients must be brought under glycemic control to improve treatment
      outcomes, but existing barriers to optimizing glycemic control must first be
      overcome, including patient nonadherence to treatment, the failure of physicians
      to intensify therapy in a timely manner, and inadequacies in the health care
      system itself. The reasons for such barriers include treatment side effects,
      complex treatment regimens, needle anxiety, poor patient education, and the
      absence of an adequate patient care plan; however, newer therapies and devices,
      combined with comprehensive care plans involving adequate patient education, can
      help to minimize barriers and improve treatment outcomes. 

PMID- 23953079
TI  - Identifying, documenting, and examining heterogeneity in systematic reviews of
      complex interventions.
AB  - This article describes approaches for planning, dealing, and analyzing
      heterogeneity in a systematic review of complex interventions. Approaches aim to
      generate a priori hypotheses of the mechanism of action of a complex intervention
      to identify the key variables that might contribute to variation among studies
      and guide statistical analysis. In addition to characteristics related to the
      population, intervention, and outcomes, we describe study-related variables, such
      as the way the interventions have been implemented and the context and conduct of
      studies. These approaches will guide reviewers planning a meta-analysis and
      provide a rationale for not meta-analyzing data if there is too much variability.
      Potential difficulties in applying meta-analytical techniques to examine
      statistical association among study results and sources of potential
      heterogeneity are described; these include the selection of a fixed or random
      effects model, the risk of multiple testing and confounding when studies include
      different aspects of a complex intervention or different subsamples of the
      intended participant pool. 

PMID- 23953080
TI  - Introducing a series of methodological articles on considering complexity in
      systematic reviews of interventions.

PMID- 23953081
TI  - Assessing the applicability of findings in systematic reviews of complex
      interventions can enhance the utility of reviews for decision making.
AB  - Assessment of applicability is an essential part of the systematic review
      process. In the context of systematic reviews of the effects of interventions,
      applicability is an assessment of whether the findings of a review can be applied
      in a particular context or population. For more complex interventions, assessing
      applicability can be challenging because of greater diversity of, and
      interactions within and between, the intended population, intervention
      components, comparison conditions, and outcomes as well as a range of further
      considerations related to intervention context and theoretical basis. We
      recommend that review authors plan and conduct analyses to explain variations in
      effect and answer questions about mechanisms of action and influence of different
      settings, contexts, and populations. We also recommend that review authors
      provide rich descriptions of the setting, implementation details, resource use,
      and contexts of included studies and assess applicability for at least one target
      population, setting, and context. This should facilitate applicability
      assessments by end users. Consensus on terminology is needed and guidance should
      be developed for the synthesis of implementation information within reviews as
      well as the documentation of applicability judgments by review authors. 

PMID- 23953082
TI  - Synthesizing evidence on complex interventions: how meta-analytical, qualitative,
      and mixed-method approaches can contribute.
AB  - OBJECTIVES: Although there is increasing interest in the evaluation of complex
      interventions, there is little guidance on how evidence from complex
      interventions may be reviewed and synthesized, and the relevance of the plethora
      of evidence synthesis methods to complexity is unclear. This article aims to
      explore how different meta-analytical approaches can be used to examine aspects
      of complexity; describe the contribution of various narrative, tabular, and
      graphical approaches to synthesis; and give an overview of the potential choice
      of selected qualitative and mixed-method evidence synthesis approaches. STUDY
      DESIGN AND SETTING: The methodological discussions presented here build on a 2
      day workshop held in Montebello, Canada, in January 2012, involving
      methodological experts from the Campbell and Cochrane Collaborations and from
      other international review centers (Anderson L, Petticrew M, Chandler J, et al.
      INTRODUCTION: systematic reviews of complex interventions. In press). These
      systematic review methodologists discussed the broad range of existing methods
      and considered the relevance of these methods to reviews of complex
      interventions. RESULTS: The evidence from primary studies of complex
      interventions may be qualitative or quantitative. There is a wide range of
      methodological options for reviewing and presenting this evidence. Specific
      contributions of statistical approaches include the use of meta-analysis, meta
      regression, and Bayesian methods, whereas narrative summary approaches provide
      valuable precursors or alternatives to these. Qualitative and mixed-method
      approaches include thematic synthesis, framework synthesis, and realist
      synthesis. A suitable combination of these approaches allows synthesis of
      evidence for understanding complex interventions. CONCLUSION: Reviewers need to
      consider which aspects of complex interventions should be a focus of their review
      and what types of quantitative and/or qualitative studies they will be including,
      and this will inform their choice of review methods. These may range from
      standard meta-analysis through to more complex mixed-method synthesis and
      synthesis approaches that incorporate theory and/or user's perspectives.

PMID- 23953083
TI  - Is complexity just too complex?

PMID- 23953084
TI  - A research and development agenda for systematic reviews that ask complex
      questions about complex interventions.
AB  - OBJECTIVES: This article outlines a research and development agenda for
      systematic reviews that ask complex questions about interventions varying in
      degree and type of complexity. STUDY DESIGN AND SETTING: Consensus development by
      key authors of articles on methodological challenges in systematic reviews of
      complex interventions, based on a 2-day workshop in Montebello, Canada, January
      2012. RESULTS: There is an urgent need for a more precise and consistently
      applied lexicon and language to disaggregate several conceptually distinct
      dimensions of "complexity." Selected current evidence synthesis methods have
      potential application in reviews where complexity is important. There is a lack
      of evaluation of methods to better understand the nature of complex interventions
      and the optimal processes of synthesizing and interpreting evidence from these
      systematic reviews. Gaps in methods, knowledge, and know-how exist, and there is
      a need for additional guidance. CONCLUSION: Understanding how complexity can
      impact on findings of systematic reviews is critical. Experience in applying
      methods that have been developed to facilitate this understanding is limited, and
      the degree to which these approaches improve the systematic review process or
      transparency is only partially understood. Future research should concentrate on
      the impact of complexity on the systematic review process and findings and on
      further methodological development.

PMID- 23953085
TI  - Complex interventions and their implications for systematic reviews: a pragmatic
      approach.
AB  - Complex interventions present unique challenges for systematic reviews. Current
      debates tend to center around describing complexity, rather than providing
      guidance on what to do about it. At a series of meetings during 2009-2012, we met
      to review the challenges and practical steps reviewer could take to incorporate a
      complexity perspective into systematic reviews. Based on this, we outline a
      pragmatic approach to dealing with complexity, beginning, as for any review, with
      clearly defining the research question(s). We argue that reviews of complex
      interventions can themselves be simple or complex, depending on the question to
      be answered. In systematic reviews and evaluations of complex interventions, it
      will be helpful to start by identifying the sources of complexity, then mapping
      aspects of complexity in the intervention onto the appropriate sources of
      evidence (such as specific types of quantitative or qualitative study). Although
      we focus on systematic reviews, the general approach is also applicable to
      primary research that is aimed at evaluating complex interventions. Although the
      examples are drawn from health care, the approach may also be applied to other
      sectors (e.g., social policy or international development). We end by concluding
      that systematic reviews should follow the principle of Occam's razor:
      explanations should be as complex as they need to be and no more. 

PMID- 23953086
TI  - Systematic reviews of complex interventions: framing the review question.
AB  - The first and most important decision in preparing any systematic review is to
      clearly frame the question the review team seeks to answer. However, this is not
      always straightforward, particularly if synthesis teams are interested in the
      effects of complex interventions. In this article, we discuss how to formulate
      good systematic review questions of complex interventions. We describe the
      rationale for developing well-formulated review questions and review the existing
      guidance on formulating review questions. We discuss that complex interventions
      can contain a mix of effective and ineffective (or even harmful) actions, which
      may interact synergistically or dysynergistically or be interdependent, and how
      these interactions and interdependencies need to be considered when formulating
      systematic review questions. We discuss complexity specifically in terms of how
      it relates to the type of question, the scope of the review (i.e., lumping vs.
      splitting debate), and specification of the intervention. We offer several
      recommendations to assist review authors in developing a definition for their
      complex intervention of interest, which is an essential first step in formulating
      the review question. We end by identifying areas in which future methodological
      research aimed at improving question formulation, especially as it relates to
      complex interventions, is needed. 

PMID- 23953087
TI  - Investigating complexity in systematic reviews of interventions by using a
      spectrum of methods.
AB  - Systematic reviews framed by PICOS (Populations, Interventions, Comparisons,
      Outcomes, and Study designs) have been valuable for synthesizing evidence about
      the effects of interventions. However, this framework is limited in its utility
      for exploring the influence of variations within populations or interventions, or
      about the mechanisms of action or causal pathways thought to mediate outcomes,
      other contextual factors that might similarly moderate outcomes, or how and when
      these mechanisms and elements interact. Valuable insights into these issues come
      from configurative as well as aggregative methods of synthesis. This article
      considers the range of evidence that can be used in systematic reviews of
      interventions to investigate complexity in terms of potential sources of
      variation in interventions and their effects, and presents a continuum of
      purposes for, and approaches to, evidence synthesis. Choosing an appropriate
      synthesis method takes into account whether the purpose of the synthesis is to
      generate, explore, or test theories. Taking complexity into account in a
      synthesis of economic evidence similarly shifts emphasis from evidence synthesis
      strategies focused on aggregation toward configurative strategies that aim to
      develop, explore, and refine (in advance of testing) theories or explanations of
      how and why interventions are more or less resource intensive, costly or cost
      effective in different settings, or when implemented in different ways. 

PMID- 23953088
TI  - Transformation mechanism of benzophenone-4 in free chlorine promoted chlorination
      disinfection.
AB  - The UV-filter BP-4 (2-hydroxy-4-methoxybenzophenone-5-sulfonic acid) has been
      frequently observed in the environment, showing high potentials to invade
      drinking water, swimming water, or wastewater reclamation treatment systems. With
      the help of high performance liquid chromatography-high resolution mass
      spectrometry and nuclear magnetic resonance spectroscopy, 10 new products from
      free chlorine-promoted BP-4 disinfection have been disclosed and their possible
      transformation routes have been investigated. The first route is chlorine
      substitution of BP-4 and its transformation products, forming mono-, di-, and tri
      chlorinated BP-4 analogs. The second is Baeyer-Villiger-Type oxidation,
      converting diphenyl ketone to phenyl ester derivatives. The third is ester
      hydrolysis, generating corresponding phenolic and benzoic products. The fourth is
      decarboxylation, replacing the carboxyl group by chloride in the benzoic-type
      intermediate. The fifth is desulfonation, degrading the sulfonic group through an
      alternative chlorine substitution on the benzene ring. Orthogonal experiments
      have been established to investigate the species transformed from BP-4 at
      different pH values and free available chlorine (FAC) dosages. The reaction
      pathways are strongly dependent on pH conditions, while an excessive amount of
      FAC eliminates BP-4 to the smaller molecules. The initial transformation of BP-4
      in chlorination system follows pseudo-first-order kinetics, and its half-lives
      ranged from 7.48 s to 1.26 * 10(2) s. More importantly, we have observed that the
      FAC-treated BP-4 aqueous solution might increase the genotoxic potentials due to
      the generation of chlorinated disinfection by-products.

PMID- 23953089
TI  - Photochemical processes involving the UV absorber benzophenone-4 (2-hydroxy-4
      methoxybenzophenone-5-sulphonic acid) in aqueous solution: reaction pathways and
      implications for surface waters.
AB  - The sunlight filter benzophenone-4 (BP-4) is present in surface waters as two
      prevailing forms, the singly deprotonated (HA-) and the doubly deprotonated one
      (A(2-)), with pKa2 = 7.30 +/- 0.14 (MU +/- sigma, by dissociation of the phenolic
      group). In freshwater environments, BP-4 would mainly undergo degradation by
      reaction with .OH and direct photolysis. The form HA(-) has a second-order
      reaction rate constant with .OH (k(.OH)) of (1.87 +/- 0.31).10(10) M(-1) s(-1)
      and direct photolysis quantum yield Phi equal to (3.2 +/- 0.6).10(-5). The form
      A(2-) has (8.46 +/- 0.24).10(9) M(-1) s(-1) as the reaction rate constant with
      .OH and (7.0 +/- 1.3).10(-5) as the photolysis quantum yield. The direct
      photolysis of HA(-) likely proceeds via homolytic breaking of the O-H bond of the
      phenolic group to give the corresponding phenoxy radical, as suggested by laser
      flash photolysis experiments. Photochemical modelling shows that because of more
      efficient direct photolysis (due to both higher sunlight absorption and higher
      photolysis quantum yield), the A(2-) form can be degraded up to 3 times faster
      than HA(-) in surface waters. An exception is represented by low-DOC (dissolved
      organic carbon) conditions, where the .OH reaction dominates degradation and the
      transformation kinetics of HA(-) is faster compared to A(2-). The half-life time
      of BP-4 in mid-latitude summertime would be in the range of days to weeks,
      depending on the environmental conditions. BP-4 also reacts with Br2(.-), and a
      rate constant k(Br2(.-),BP-4) = (8.05 +/- 1.33).10(8) M(-1) s(-1) was measured at
      pH 7.5. Model results show that reaction with Br2(.-) could be a potentially
      important transformation pathway of BP-4 in bromide-rich (e.g. seawater) and DOM
      rich environments.

PMID- 23953090
TI  - Galectin signature in normal pregnancy and preeclampsia.
AB  - Members of the galectin family are expressed within the female reproductive tract
      and have been shown to be involved in multiple biological functions that support
      the progression of pregnancy. Specific expression patterns of different members
      of this family have been identified at the maternal decidua and on the placental
      side. In some cases, mechanisms by which galectins exert their functions have
      been delineated in adverse pregnancy outcomes. This review summarizes studies on
      galectins that have been documented to be important for pregnancy maintenance,
      either supporting the maternal adaptation to pregnancy or the placentation
      process. In addition, we focus our discussion on the role of galectins in
      preeclampsia, a specific life-threatening pregnancy disorder. 

PMID- 23953091
TI  - Evaluating patient presentations for care delivered by emergency nurse
      practitioners: a retrospective analysis of 12 months.
AB  - BACKGROUND: The delivery of quality patients care in the emergency department
      (ED) is emerging as one of the most important service indicators to be measured
      in health services today. The emergency nurse practitioner role was implemented
      as a service innovation in one Melbourne, ED, Australia, in July 2004. The
      primary aim of the role was intended to enhance healthcare services, improve the
      efficiency and timely delivery of high quality care to patients. AIM: To conduct
      a retrospective study of patient presentations at the ED to obtain a profile of
      the characteristics of patients managed by emergency nurse practitioners.
      Specifically the objectives of the study were to: (1) examine the demographics of
      the patient population and (2) evaluate data on emergency department service
      indicators for this patient cohort. METHOD: A descriptive exploratory design was
      used. All patients presenting to the ED from January 01, 2011 to December 31,
      2011 and managed by emergency nurse practitioners were included in the review.
      Data collection included baseline demographics, waiting times to be seen, length
      of stay, ED discharge diagnoses and referral patterns. Data were extracted and
      imported directly from the ED patient information system (Cerner log), for the
      specified time frame. RESULTS: A total of 5212 patients were reviewed in the
      study period. The median age of patients was 35 years and 61% of patients were
      male. The most common discharge diagnosis was open wounds to hand/wrist. Waiting
      times to be seen by the emergency nurse practitioner were 14 min and length of
      stay for patients with a discharge disposition of home were 122 min. CONCLUSIONS:
      This study has provided information on patient baseline characteristics and
      performance on important service indicators for this patient sample that will
      inform further research to evaluate specific outcomes of the emergency nurse
      practitioner service.

PMID- 23953092
TI  - A critical discussion of the concept of recovery for mental health consumers in
      the Emergency Department.
AB  - BACKGROUND: The Emergency Department has increasingly become the initial point of
      contact for mental health crisis assessment and intervention, and is the
      interface between community and inpatient care. Questions regarding the
      appropriateness of the Emergency Department in providing a suitable environment
      for people who have a mental health issue abound with commentary regarding the
      confidence and competence of general Registered Nurses to provide mental health
      care. Emergency Departments are busy noisy places where rapid assessments and
      response is the norm and is counterintuitive to contemporary mental health care.
      The model of care currently considered best practice in mental health is the
      Recovery-oriented model; a long term individualised approach to collaborative
      care. The notion of Recovery as understood and practised in contemporary mental
      health care is almost polarised to that which is embedded in generalist Emergency
      Registered Nurses' practice. As Emergency Departments play an integral role in
      the assessment of people experiencing mental illness, close collaboration and
      support is required between emergency and mental health specialities to achieve
      optimal client outcomes in an environment that is nested within the medical
      model. Furthermore, Emergency Department staff must be supported in acquiring the
      knowledge and skills required to care for and manage people with a mental health
      issue. This includes cognisance and understanding of the Recovery-oriented model
      of care which is the model of care considered best practice for this client
      group. This paper offers a critical discussion of the concept of recovery for
      mental health consumers in the Emergency Department.

PMID- 23953093
TI  - Exploring staff willingness to attend work during a disaster: a study of nurses
      employed in four Australian emergency departments.
AB  - BACKGROUND: Much of the literature about emergency nurses willingness to work
      during disasters has been from a non-Australian perspective. Despite the many
      recent disasters, little is known of Australian nurse's willingness to
      participate in disaster response. This paper presents findings from a study that
      explored nurses willingness to attend work during a disaster and the factors that
      influenced this decision. METHODS: Data were collected consecutively using a
      combination of focus group and interview methods. Participants in this study,
      registered nurses from emergency departments, were recruited through convenience
      sampling from four hospitals in Australia. Participant narrative was
      electronically recorded, transcribed and thematically analysed. RESULTS: The
      participants for both the focus groups and interviews compromised a mix of ages,
      genders and years of experience as emergency nurses from across four
      jurisdictions within Australia. Three major themes that influenced willingness
      emerged with a number of subthemes. Theme one reflected the uncertainty of the
      situation such as the type of disaster. The second theme surrounded the
      preparedness of the workplace, emergency nurse and colleagues, and the third
      theme considered personal and professional choice based on home and work
      circumstances and responsibilities. CONCLUSIONS: The decision to attend work or
      not during a disaster, includes a number of complex personal, work-related and
      professional factors that can change, depending on the type of disaster,
      preparedness of the work environment and the emergency nurses' personal
      responsibilities at that time.

PMID- 23953094
TI  - Nurse practitioners treating ankle and foot injuries using the Ottawa Ankle
      Rules: a comparative study in the emergency department.
AB  - BACKGROUND: Nurse practitioners (NPs) in the Emergency Department (ED) have been
      trained to assess a range of clinical problems and minor complaints such as acute
      ankle injury. This study compared assessment of suspected ankle and foot injuries
      using the Ottawa Ankle Rules (OAR) by NPs and ED medical doctors (ED-Drs).
      METHODS: A prospective, comparative, observational study was undertaken in an
      Australian acute adult and paediatric urban district ED. NPs and ED-Drs recorded
      information for patients with acute ankle and/or mid-foot injuries on demographic
      characteristics, OAR features, use of X-ray and patient management. Outcome
      measures included X-ray rates and identification of fracture. RESULTS: 174
      patients were included in this study: 51 received NP and 123 received ED-Dr care.
      Assessed as requiring X-ray assessment (NP: 78.4%, ED-Dr: 88.6%; p=0.081), and
      detection of significant fracture (NP: 17.6%, ED-Dr: 22.8%; p=0.453) were
      similar. ED-based medical registrars were more likely to miss a fracture compared
      with NP (NP: 0%, ED-based Registrar: 28.6%, p=0.013). There were no significant
      differences in rates of OAR features for patients seen by NPs or ED-Drs.
      CONCLUSION: This study suggests that NPs are less likely to miss significant
      fractures of the ankle and/or foot compared with ED-based medical registrars.
      Future research should focus on actual use of the OAR and accuracy of X-ray
      assessment by NPs.

PMID- 23953095
TI  - Management of health care services for flood victims: the case of the shelter at
      Nakhon Pathom Rajabhat University Central Thailand.
AB  - BACKGROUND: In Central Thailand basic health care services were affected by a
      natural disaster in the form of a flood situation. Flood Relief Operations
      Centers were established from the crisis. Nakhon Pathom Rajabhat University and
      including the faculty of nursing volunteered to care for those affected and
      assist in re-establishing a functioning health care system. STUDY OBJECTIVES: The
      aim of this study was to make explicit knowledge of concept, lesson learned, and
      the process of management for re-establishing a health care service system at a
      flood victims at Relief Operations Center, Nakhon Pathom Rajabhat University.
      METHODS: We used a qualitative design with mixed methods. This involved in-depth
      interviews, focus group, observational participation and non-observational
      participation. Key informants included university administrators, instructors,
      leaders of flood victims and the flood victims. Data was collected during October
      December, 2010. Data were analysed using content analysis and compared matrix.
      RESULTS: We found that the concept and principle of health care services
      management were community based and involved home care and field hospital
      services. We had prepared a management system that placed emphasise on a
      community based approach and holistic caring such as 24h Nursing Clinic Home,
      visits with family, a referral system, field hospital. The core of management was
      to achieve integrated instruction started from nursing students were practiced
      skills as Health promotion and nursing techniques practicum. CONCLUSIONS: Rules
      were established regarding the health care service system. The outcomes of Health
      Care Service at the Flood Relief Operations Center were direct and sincere help
      without conditions, administrations concerned and volunteer nursing students
      instructors, University Officer have sympathetic and charitable with flood
      victims and environment.

PMID- 23953096
TI  - Breast sensibility after bilateral risk-reducing mastectomy and immediate breast
      reconstruction: a prospective study.
AB  - The demand for risk-reducing mastectomy (RRM) to avoid breast cancer has
      increased over the last several years, and knowledge of the outcome after this
      prophylactic surgical procedure is important. The primary aim of this study was
      to prospectively compare breast sensibility before and after RRM in a consecutive
      series of women. The study also investigated whether the nipples were less numb
      if the nipple areola complexes (NACs) were spared compared with regrafted nipple
      tips. Forty-six women who selected bilateral RRM with immediate reconstruction
      using implants at the Karolinska University Hospital, Solna, Stockholm, Sweden,
      were included in the study. The median patient age at the time of surgery was 39
      years (range 26-58). All patients were evaluated preoperatively and at least 2
      years postoperatively (median 29 months). Tactile, thermal and nociceptive
      cutaneous sensibilities were studied with quantitative techniques. The patients
      at the postoperative evaluation completed a questionnaire about subjective
      feelings in both breasts. The results showed that breast sensibility is
      significantly impaired after RRM. Additionally, the ability to experience sexual
      sensations in the breast is often lost. An NAC-sparing surgery did not result in
      better nipple sensibility. 

PMID- 23953097
TI  - Working-age cataract patients: visual results, reading performance, and quality
      of life with three diffractive multifocal intraocular lenses.
AB  - PURPOSE: To compare the visual outcomes, reading performance, and quality of life
      (QoL) of working-age cataractous patients bilaterally implanted with 3 different
      diffractive multifocal intraocular lenses (MIOLs). DESIGN: Two-center,
      randomized, prospective, double-masked study. PARTICIPANTS: Sixty-three
      consecutive patients (126 eyes) seen at Ophthalmology Section, Palermo and
      Florence University, Italy, randomized to receive the ReSTOR SN6AD3 (Alcon
      Laboratories, Inc, Irvine, CA) (20 patients, group A), ReSTOR SN6AD1 (Alcon
      Laboratories, Inc) (21 patients, group B), or TECNIS ZMA00 (Abbott Medical
      Optics, Santa Ana, CA) (22 patients, group C) MIOL. INTERVENTION:
      Phacoemulsification. MAIN OUTCOME MEASURES: One-year follow-up differences among
      the 3 MIOL groups in visual acuity, reading performance by MNREAD (Minnesota
      Laboratory for Low-Vision Research, University of Minnesota, Minneapolis, MN)
      reading acuity (RA), critical print size (CPS), and maximum reading speed (MRS)
      under mesopic and photopic conditions. SECONDARY OUTCOME MEASURES: Photopic and
      mesopic contrast sensitivity (CS) by Pelli-Robson test and patient satisfaction
      by National Eye Institute Refractive Error Quality of Life Instrument-42 (NEI RQL
      42) questionnaire. RESULTS: Mean photopic uncorrected near visual acuity (UNVA),
      distance-corrected near visual acuity (DCNVA), and corrected near visual acuity
      (CNVA) did not differ among groups, with a preferred reading distance greater in
      group B (P< 0.0005). Photopic distance-corrected intermediate visual acuity
      (DCIVA) was best in group B (P = 0.001) and better in group C than in group A.
      Mesopic UNVA and DCNVA were worse in groups A and B compared with group C (P<
      0.0005 in both cases), with better DCNVA in group B than in group A (P = 0.031).
      Mesopic uncorrected intermediate visual acuity (UIVA) and DCIVA were worst in
      group A, with better results in group C (P< 0.0005 and P = 0.001, respectively).
      Mesopic MNREAD RA was better in group C (P = 0.02), and mesopic MRS was higher in
      groups B and C than in group A (P = 0.002). The QoL scores by the NEI RQL-42 test
      exhibited no differences among groups in 9 over 13 scales. "Near vision" (P =
      0.005), "symptoms" (P = 0.001), and "satisfaction with correction" scale scores
      (P = 0.030) were lowest in group A, and "appearance" scale score was lowest in
      group B (P = 0.045). CONCLUSIONS: Newer-generation aspheric diffractive MIOLs,
      especially low-add hybrid apodized or full diffractive, are highly suited for
      working-age cataractous patients in terms of visual outcomes, reading
      performance, and QoL. Intrinsic optical differences, such as optimization for
      computer or dim-light working, or night driving, could be useful tools to
      customize the IOL in each single case.

PMID- 23953098
TI  - Prevalence of myopia, hyperopia, and astigmatism in non-Hispanic white and Asian
      children: multi-ethnic pediatric eye disease study.
AB  - PURPOSE: To determine the age-, gender-, and ethnicity-specific prevalence of
      myopia, hyperopia, and astigmatism in non-Hispanic white (NHW) and Asian
      preschool children. DESIGN: Population-based, cross-sectional study.
      PARTICIPANTS: A population-based sample of 1501 NHW children and 1507 Asian
      children aged 6-72 months from Los Angeles County and Riverside County,
      California. METHODS: Eligible children underwent an in-home and in-clinic
      interview and a comprehensive eye examination including cycloplegic
      autorefraction from 100 census tracts. MAIN OUTCOME MEASURES: The proportion of
      children with myopia (spherical equivalent [SE] <=-1.00 diopter [D]), hyperopia
      (SE >= +2.00 D) and cylindrical refractive error >=1.50 D in the worse eye. The
      astigmatism type was defined as with-the-rule (WTR; +cylinder axis 90 degrees +/
      15 degrees ) and against-the-rule (ATR; + cylinder axis 180 degrees +/-15 degrees
      ); all other orientations were considered oblique (OBL). RESULTS: The prevalence
      of myopia, hyperopia, and astigmatism in NHW children was 1.20% (95% confidence
      interval [CI], 0.76%-1.89%), 25.65% (95% CI, 23.5%-27.9%), and 6.33% (95% CI,
      5.21%-7.68%), respectively. The prevalence of WTR, ATR, and OBL astigmatism in
      NHW children was 4.33%, 1.00%, and 1.00%, respectively. Prevalence was lower with
      older age groups for astigmatism (P = 0.0002), but not for myopia (P = 0.82) or
      hyperopia (P = 0.31). In Asian children, the prevalence of myopia, hyperopia, and
      astigmatism was 3.98% (95% CI, 3.11%-5.09%), 13.47% (95% CI, 11.8%-15.3%), and
      8.29% (95% CI, 7.01%-9.80%), respectively. The prevalence of WTR, ATR, and OBL
      astigmatism was 6.50%, 0.80%, and 1.00% respectively. The prevalence of hyperopia
      was higher in girls than boys (P = 0.0002), but no differences were found for
      myopia and astigmatism. CONCLUSIONS: Hyperopia was the most common refractive
      error in both Asian and NHW children. However, compared with NHW children, myopia
      was relatively more prevalent, and hyperopia less prevalent, among Asian
      children. The prevalence of astigmatism was greatest in infants, and WTR
      astigmatism predominated at all ages. Myopia showed relatively stable prevalence
      across age groups, whereas hyperopia prevalence decreased after infancy and then
      increased again in older age groups; however, longitudinal studies are needed to
      evaluate refractive changes over time in individual children. FINANCIAL
      DISCLOSURE(S): The authors have no proprietary or commercial interest in any of
      the materials discussed in this article.

PMID- 23953099
TI  - Expanded criteria for pneumatic retinopexy and potential cost savings.
AB  - PURPOSE: To provide insight into the preoperative factors that affect outcome
      after pneumatic retinopexy (PR) for treatment of primary rhegmatogenous retinal
      detachment repair. Additionally, we sought to analyze the cost of rhegmatogenous
      retinal detachment repair in the United States to determine potential cost
      savings with pneumatic retinopexy. DESIGN: Single-center, retrospective,
      observational consecutive case series and third party payer-perspective
      comparative cost analysis. PARTICIPANTS: We included 141 eyes undergoing
      pneumatic retinopexy for the treatment of primary rhegmatogenous retinal
      detachment. METHODS: Preoperative characteristics, anatomic outcomes, and best
      available visual acuity were collected. Anatomic and visual outcomes were
      analyzed based on the presence of selected preoperative factors. The primary
      cohort was divided into 2 groups based on preoperative characteristics: (1)
      traditional pneumatic retinopexy and (2) nontraditional pneumatic retinopexy.
      Comparative cost analyses were performed between pneumatic retinopexy, scleral
      buckling, and vitrectomy. MAIN OUTCOME MEASURES: Anatomic and visual outcomes at
      6 months. RESULTS: Overall anatomic success was 78.7% and visual acuity improved
      significantly (logarithm of the minimum angle of resolution [logMAR] 0.48-0.25; P
      <0.005). A 97.6% final anatomic success rate was achieved. Anatomic outcomes were
      similar between traditional versus nontraditional (84.1% vs 74.4%; P = 0.16),
      phakic versus pseudophakic (79.1% vs 78.0%; P = 0.88), and macula-on versus
      macula-off (77.9% vs 81.1%; P = 0.68) groups. Anatomic failure was predicted by
      the presence of an inferior retinal break (P <0.005) or visible vitreous traction
      on a retinal break (P = 0.04). Visual outcomes were similar between each of the
      traditional versus nontraditional (logMAR 0.21 vs 0.27; P >0.05) and phakic
      versus pseudophakic groups (logMAR 0.23 vs 0.28; P >0.05). Visual outcomes were
      better in macula-on detachments compared with those in which the macula was
      detached (logMAR 0.18 vs 0.42; P <0.005). Annual health care cost savings in the
      United States ranging from $6 to $30 million are theoretically possible by
      increasing pneumatic retinopexy utilization from the current rate of 15% to 20%
      35%. CONCLUSIONS: Pneumatic retinopexy is an effective treatment modality for
      primary rhegmatogenous retinal detachment. Anatomic and visual outcomes are
      similar for traditional and nontraditional preoperative inclusion criteria, as
      well as phakic and pseudophakic eyes. Inferior breaks and visible vitreous
      traction on a tear predicted failure. Increased utilization of pneumatic
      retinopexy would achieve significant cost savings while maintaining outcomes.

PMID- 23953100
TI  - Vascular endothelial growth factor gene and the response to anti-vascular
      endothelial growth factor treatment for choroidal neovascularization in high
      myopia.
AB  - PURPOSE: To investigate the association between the vascular endothelial growth
      factor (VEGF) gene polymorphism and the response to anti-VEGF treatment for
      choroidal neovascularization (CNV) in highly myopic eyes. DESIGN: Retrospective
      cohort study. PARTICIPANTS: A total of 357 unrelated highly myopic Japanese
      patients with axial lengths >=26.0 mm in both eyes were eligible, and 83 patients
      who received anti-VEGF therapy for CNV and could be followed for more than 1 year
      were included. METHODS: We genotyped a functional single nucleotide polymorphism
      in the VEGF gene, rs2010963. The associations between the distribution of the
      rs2010963 genotype and the number of eyes with maintained or improved visual
      acuity (VA) were analyzed. Furthermore, multivariable logistic regression
      analysis was performed to adjust for 7 possible prognostic factors, including
      age, sex, CNV size, CNV location, administration of loading dose, pretreatment
      VA, and number of additional treatments. MAIN OUTCOME MEASURES: The primary end
      point was maintenance of VA, and secondary end points were progression of
      chorioretinal atrophy (CRA) and recurrence of CNV. RESULTS: Mean age and mean
      axial length were not significantly different among 3 genotypes of rs2010963. The
      percentage of eyes with maintained or improved VA was significantly higher with
      the G allele of rs2010963 (P =0.016), and stepwise analysis revealed that both
      rs2010963 and CNV size were associated with VA maintenance (P =0.040 and 0.033,
      respectively). The secondary analysis revealed that administration of a loading
      dose was significantly associated with both CRA progression (P =0.031) and
      recurrence of CNV (P =0.020), whereas rs2010963 was not. CONCLUSIONS: These
      results suggest that the VEGF polymorphism influences the VA prognosis in highly
      myopic eyes with CNV within 1 year after anti-VEGF treatment. This association
      was still observed after removing its confounding effect through CNV size. The
      rs2010963 polymorphism was not associated with CNV recurrence or CRA progression,
      which indicates that these changes are not tied to intrinsic factors and may be
      controllable by improving treatment methods.

PMID- 23953102
TI  - [Erythematous-brownish macules and papules in a patient with human
      immunodeficiency virus infection].

PMID- 23953101
TI  - Role of corneal collagen cross-linking in pseudophakic bullous keratopathy: a
      clinicopathological study.
AB  - OBJECTIVE: To evaluate the clinical and histopathologic changes induced by
      collagen cross-linking (CXL) in pseudophakic bullous keratopathy (PBK). DESIGN:
      Randomized, prospective, interventional study. PARTICIPANTS: Twenty-four patients
      with PBK were included in the study. METHODS: Twenty-four patients with PBK
      underwent CXL followed by keratoplasty at 1 or 3 months. Twelve patients
      underwent penetrating keratoplasty 1 month after CXL (group A) and the remaining
      12 patients underwent penetrating keratoplasty 3 months after CXL (group B). The
      main outcome measures were assessed at 1 week and 1 month for all patients and at
      3 months for 12 patients only. The corneal buttons underwent histopathologic and
      immunofluorescence evaluation. MAIN OUTCOME MEASURES: Visual acuity, ocular
      discomfort (tearing, redness, pain), corneal haze, central corneal thickness,
      histopathologic evaluation, and immunofluorescent microscopy. RESULTS: Mean
      visual acuity showed a significant improvement after CXL, from 1.925 +/- 0.173
      before surgery to 1.75+/-0.296 at 1 month after surgery (P = 0.010), but
      deteriorated to 1.81 +/- 0.23 at 3 months. Symptomatic relief after CXL was at a
      maximum at 1 month, with a worsening trend at 3 months. Eighteen patients showed
      a reduction in corneal haze 1 month after CXL. The effect was maintained in 9 of
      12 patients at 3 months. The mean central corneal thickness decreased
      significantly from 846.46 +/- 88.741 to 781.0 +/- 98.788 MUm at 1 month (P<0.01)
      after CXL, but increased to 805.08+/-136.06 MUm at 3 months. Immunofluorescence
      microscopy revealed anterior stromal compaction in 7 of 12 patients (58.3%) in
      group A and in 5 of 12 patients (41.6%) in group B. Staining of keratocyte nuclei
      with 4',6-diaminido-2-phenylindole dihydrochloride (Molecular Probes, Carlsband,
      CA) revealed a relative uniform distribution throughout the stroma. CONCLUSIONS:
      Collagen cross-linking causes symptomatic relief and a decrease in central
      corneal thickness and anterior stromal compaction in PBK. However, the effect
      decreases with time and depends on disease severity.

PMID- 23953103
TI  - Mechanistic interpretation of promoter-proximal peaks and RNAPII density maps.

PMID- 23953104
TI  - Bumping up kinase activity with an ATP-derived neo-substrate.
AB  - Pharmacologic agents capable of increasing kinase function would be useful for
      treating diseases associated with reduced kinase activity, such as inherited
      forms of Parkinson's disease. In this issue, Hertz et al. report an innovative
      approach for activating the Parkinson's-associated kinase PINK1 in cells with an
      ATP-derived neo-substrate.

PMID- 23953105
TI  - A cluster to remember.
AB  - Based on a massive transcription factor location analysis within a single cell
      type, in this issue Yan et al. find that the great majority of occupancies occur
      within dense clusters of up to 100 factors that almost invariably contain
      cohesins. Retention of cohesins at cluster sites during mitosis raises the
      possibility that they contribute to transcriptional memory during the cell cycle.

PMID- 23953106
TI  - Of origins and pedigrees: lineage tracing of dendritic cells.
AB  - Understanding the ontogeny of distinct hematopoietic cell types remains a
      challenge. In this issue, Schraml et al. contribute to unraveling the complexity
      of a central component of the mononuclear phagocyte system by using a new in vivo
      approach to trace the progeny of common dendritic cell precursors.

PMID- 23953107
TI  - Single-molecule approaches embrace molecular cohorts.
AB  - Enormous mechanistic insight has been gained by studying the behavior of single
      molecules. The same approaches used to study proteins in isolation are now being
      leveraged to examine the changes in functional behavior that emerge when single
      molecules have company.

PMID- 23953108
TI  - Altered ribostasis: RNA-protein granules in degenerative disorders.
AB  - The molecular processes that contribute to degenerative diseases are not well
      understood. Recent observations suggest that some degenerative diseases are
      promoted by the accumulation of nuclear or cytoplasmic RNA-protein (RNP)
      aggregates, which can be related to endogenous RNP granules. RNP aggregates arise
      commonly in degenerative diseases because RNA-binding proteins commonly self
      assemble, in part through prion-like domains, which can form self-propagating
      amyloids. RNP aggregates may be toxic due to multiple perturbations of
      posttranscriptional control, thereby disrupting the normal "ribostasis" of the
      cell. This suggests that understanding and modulating RNP assembly or clearance
      may be effective approaches to developing therapies for these diseases.

PMID- 23953109
TI  - A neo-substrate that amplifies catalytic activity of parkinson's-disease-related
      kinase PINK1.
AB  - Mitochondria have long been implicated in the pathogenesis of Parkinson's disease
      (PD). Mutations in the mitochondrial kinase PINK1 that reduce kinase activity are
      associated with mitochondrial defects and result in an autosomal-recessive form
      of early-onset PD. Therapeutic approaches for enhancing the activity of PINK1
      have not been considered because no allosteric regulatory sites for PINK1 are
      known. Here, we show that an alternative strategy, a neo-substrate approach
      involving the ATP analog kinetin triphosphate (KTP), can be used to increase the
      activity of both PD-related mutant PINK1(G309D) and PINK1(WT). Moreover, we show
      that application of the KTP precursor kinetin to cells results in biologically
      significant increases in PINK1 activity, manifest as higher levels of Parkin
      recruitment to depolarized mitochondria, reduced mitochondrial motility in axons,
      and lower levels of apoptosis. Discovery of neo-substrates for kinases could
      provide a heretofore-unappreciated modality for regulating kinase activity.

PMID- 23953110
TI  - Structural rearrangement of ebola virus VP40 begets multiple functions in the
      virus life cycle.
AB  - Proteins, particularly viral proteins, can be multifunctional, but the mechanisms
      behind multifunctionality are not fully understood. Here, we illustrate through
      multiple crystal structures, biochemistry, and cellular microscopy that VP40
      rearranges into different structures, each with a distinct function required for
      the ebolavirus life cycle. A butterfly-shaped VP40 dimer traffics to the cellular
      membrane. Once there, electrostatic interactions trigger rearrangement of the
      polypeptide into a linear hexamer. These hexamers construct a multilayered,
      filamentous matrix structure that is critical for budding and resembles tomograms
      of authentic virions. A third structure of VP40, formed by a different
      rearrangement, is not involved in virus assembly but instead uniquely binds RNA
      to regulate viral transcription inside infected cells. These results provide a
      functional model for ebolavirus matrix assembly and the other roles of VP40 in
      the virus life cycle and demonstrate how a single wild-type, unmodified
      polypeptide can assemble into different structures for different functions.

PMID- 23953112
TI  - Transcription factor binding in human cells occurs in dense clusters formed
      around cohesin anchor sites.
AB  - During cell division, transcription factors (TFs) are removed from chromatin
      twice, during DNA synthesis and during condensation of chromosomes. How TFs can
      efficiently find their sites following these stages has been unclear. Here, we
      have analyzed the binding pattern of expressed TFs in human colorectal cancer
      cells. We find that binding of TFs is highly clustered and that the clusters are
      enriched in binding motifs for several major TF classes. Strikingly, almost all
      clusters are formed around cohesin, and loss of cohesin decreases both DNA
      accessibility and binding of TFs to clusters. We show that cohesin remains bound
      in S phase, holding the nascent sister chromatids together at the TF cluster
      sites. Furthermore, cohesin remains bound to the cluster sites when TFs are
      evicted in early M phase. These results suggest that cohesin-binding functions as
      a cellular memory that promotes re-establishment of TF clusters after DNA
      replication and chromatin condensation.

PMID- 23953111
TI  - Precise developmental gene expression arises from globally stochastic
      transcriptional activity.
AB  - Early embryonic patterning events are strikingly precise, a fact that appears
      incompatible with the stochastic gene expression observed across phyla. Using
      single-molecule mRNA quantification in Drosophila embryos, we determine the
      magnitude of fluctuations in the expression of four critical patterning genes.
      The accumulation of mRNAs is identical across genes and fluctuates by only ~8%
      between neighboring nuclei, generating precise protein distributions. In
      contrast, transcribing loci exhibit an intrinsic noise of ~45% independent of
      specific promoter-enhancer architecture or fluctuating inputs. Precise transcript
      distribution in the syncytium is recovered via straightforward spatiotemporal
      averaging, i.e., accumulation and diffusion of transcripts during nuclear cycles,
      without regulatory feedback. Common expression characteristics shared between
      genes suggest that fluctuations in mRNA production are context independent and
      are a fundamental property of transcription. The findings shed light on how the
      apparent paradox between stochastic transcription and developmental precision is
      resolved.

PMID- 23953113
TI  - The yeast ski complex: crystal structure and RNA channeling to the exosome
      complex.
AB  - The Ski complex is a conserved multiprotein assembly required for the cytoplasmic
      functions of the exosome, including RNA turnover, surveillance, and interference.
      Ski2, Ski3, and Ski8 assemble in a tetramer with 1:1:2 stoichiometry. The crystal
      structure of an S. cerevisiae 370 kDa core complex shows that Ski3 forms an array
      of 33 TPR motifs organized in N-terminal and C-terminal arms. The C-terminal arm
      of Ski3 and the two Ski8 subunits position the helicase core of Ski2 centrally
      within the complex, enhancing RNA binding. The Ski3 N-terminal arm and the Ski2
      insertion domain allosterically modulate the ATPase and helicase activities of
      the complex. Biochemical data suggest that the Ski complex can thread RNAs
      directly to the exosome, coupling the helicase and the exoribonuclease through a
      continuous RNA channel. Finally, we identify a Ski8-binding motif common to Ski3
      and Spo11, rationalizing the moonlighting properties of Ski8 in mRNA decay and
      meiosis.

PMID- 23953114
TI  - Adult c-kit(pos) cardiac stem cells are necessary and sufficient for functional
      cardiac regeneration and repair.
AB  - The epidemic of heart failure has stimulated interest in understanding cardiac
      regeneration. Evidence has been reported supporting regeneration via
      transplantation of multiple cell types, as well as replication of postmitotic
      cardiomyocytes. In addition, the adult myocardium harbors endogenous c-kit(pos)
      cardiac stem cells (eCSCs), whose relevance for regeneration is controversial.
      Here, using different rodent models of diffuse myocardial damage causing acute
      heart failure, we show that eCSCs restore cardiac function by regenerating lost
      cardiomyocytes. Ablation of the eCSC abolishes regeneration and functional
      recovery. The regenerative process is completely restored by replacing the
      ablated eCSCs with the progeny of one eCSC. eCSCs recovered from the host and
      recloned retain their regenerative potential in vivo and in vitro. After
      regeneration, selective suicide of these exogenous CSCs and their progeny
      abolishes regeneration, severely impairing ventricular performance. These data
      show that c-kit(pos) eCSCs are necessary and sufficient for the regeneration and
      repair of myocardial damage.

PMID- 23953115
TI  - Genetic tracing via DNGR-1 expression history defines dendritic cells as a
      hematopoietic lineage.
AB  - Mononuclear phagocytes are classified as macrophages or dendritic cells (DCs)
      based on cell morphology, phenotype, or select functional properties. However,
      these attributes are not absolute and often overlap, leading to difficulties in
      cell-type identification. To circumvent this issue, we describe a mouse model to
      define DCs based on their ontogenetic descendence from a committed precursor. We
      show that precursors of mouse conventional DCs, but not other leukocytes, are
      marked by expression of DNGR-1. Genetic tracing of DNGR-1 expression history
      specifically marks cells traditionally ascribed to the DC lineage, and this
      restriction is maintained after inflammation. Notably, in some tissues, cells
      previously thought to be monocytes/macrophages are in fact descendants from DC
      precursors. These studies provide an in vivo model for fate mapping of DCs,
      distinguishing them from other leukocyte lineages, and thus help to unravel the
      functional complexity of the mononuclear phagocyte system.

PMID- 23953116
TI  - Inhibition of mTORC1 by astrin and stress granules prevents apoptosis in cancer
      cells.
AB  - Mammalian target of rapamycin complex 1 (mTORC1) controls growth and survival in
      response to metabolic cues. Oxidative stress affects mTORC1 via inhibitory and
      stimulatory inputs. Whereas downregulation of TSC1-TSC2 activates mTORC1 upon
      oxidative stress, the molecular mechanism of mTORC1 inhibition remains unknown.
      Here, we identify astrin as an essential negative mTORC1 regulator in the
      cellular stress response. Upon stress, astrin inhibits mTORC1 association and
      recruits the mTORC1 component raptor to stress granules (SGs), thereby preventing
      mTORC1-hyperactivation-induced apoptosis. In turn, balanced mTORC1 activity
      enables expression of stress factors. By identifying astrin as a direct molecular
      link between mTORC1, SG assembly, and the stress response, we establish a
      unifying model of mTORC1 inhibition and activation upon stress. Importantly, we
      show that in cancer cells, apoptosis suppression during stress depends on astrin.
      Being frequently upregulated in tumors, astrin is a potential clinically relevant
      target to sensitize tumors to apoptosis.

PMID- 23953117
TI  - Exploitation of latent allostery enables the evolution of new modes of MAP kinase
      regulation.
AB  - Allosteric interactions provide precise spatiotemporal control over signaling
      proteins, but how allosteric activators and their targets coevolve is poorly
      understood. Here, we trace the evolution of two allosteric activator motifs
      within the yeast scaffold protein Ste5 that specifically target the mating MAP
      kinase Fus3. One activator (Ste5-VWA) provides pathway insulation and dates to
      the divergence of Fus3 from its paralog, Kss1; a second activator (Ste5-FBD) that
      tunes mating behavior is, in contrast, not conserved in most lineages.
      Surprisingly, both Ste5 activator motifs could regulate MAP kinases that diverged
      from Fus3 prior to the emergence of Ste5, suggesting that Ste5 activators arose
      by exploiting latent regulatory features already present in the MAPK ancestor.
      The magnitude of this latent allosteric potential drifts widely among pre-Ste5
      MAP kinases, providing a pool of hidden phenotypic diversity that, when revealed
      by new activators, could lead to functional divergence and to the evolution of
      distinct signaling behaviors.

PMID- 23953119
TI  - Chromatin position effects assayed by thousands of reporters integrated in
      parallel.
AB  - Reporter genes integrated into the genome are a powerful tool to reveal effects
      of regulatory elements and local chromatin context on gene expression. However,
      so far such reporter assays have been of low throughput. Here, we describe a
      multiplexing approach for the parallel monitoring of transcriptional activity of
      thousands of randomly integrated reporters. More than 27,000 distinct reporter
      integrations in mouse embryonic stem cells, obtained with two different
      promoters, show ~1,000-fold variation in expression levels. Data analysis
      indicates that lamina-associated domains act as attenuators of transcription,
      likely by reducing access of transcription factors to binding sites. Furthermore,
      chromatin compaction is predictive of reporter activity. We also found evidence
      for crosstalk between neighboring genes and estimate that enhancers can influence
      gene expression on average over ~20 kb. The multiplexed reporter assay is highly
      flexible in design and can be modified to query a wide range of aspects of gene
      regulation.

PMID- 23953118
TI  - Developmental fate and cellular maturity encoded in human regulatory DNA
      landscapes.
AB  - Cellular-state information between generations of developing cells may be
      propagated via regulatory regions. We report consistent patterns of gain and loss
      of DNase I-hypersensitive sites (DHSs) as cells progress from embryonic stem
      cells (ESCs) to terminal fates. DHS patterns alone convey rich information about
      cell fate and lineage relationships distinct from information conveyed by gene
      expression. Developing cells share a proportion of their DHS landscapes with
      ESCs; that proportion decreases continuously in each cell type as differentiation
      progresses, providing a quantitative benchmark of developmental maturity.
      Developmentally stable DHSs densely encode binding sites for transcription
      factors involved in autoregulatory feedback circuits. In contrast to normal
      cells, cancer cells extensively reactivate silenced ESC DHSs and those from
      developmental programs external to the cell lineage from which the malignancy
      derives. Our results point to changes in regulatory DNA landscapes as
      quantitative indicators of cell-fate transitions, lineage relationships, and
      dysfunction.

PMID- 23953120
TI  - A nanobody-based system using fluorescent proteins as scaffolds for cell-specific
      gene manipulation.
AB  - Fluorescent proteins are commonly used to label cells across organisms, but the
      unmodified forms cannot control biological activities. Using GFP-binding proteins
      derived from Camelid antibodies, we co-opted GFP as a scaffold for inducing
      formation of biologically active complexes, developing a library of hybrid
      transcription factors that control gene expression only in the presence of GFP or
      its derivatives. The modular design allows for variation in key properties such
      as DNA specificity, transcriptional potency, and drug dependency. Production of
      GFP controlled cell-specific gene expression and facilitated functional
      perturbations in the mouse retina and brain. Further, retrofitting existing
      transgenic GFP mouse and zebrafish lines for GFP-dependent transcription enabled
      applications such as optogenetic probing of neural circuits. This work
      establishes GFP as a multifunctional scaffold and opens the door to selective
      manipulation of diverse GFP-labeled cells across transgenic lines. This approach
      may also be extended to exploit other intracellular products as cell-specific
      scaffolds in multicellular organisms.

PMID- 23953121
TI  - SnapShot: Class I PI3K isoform signaling.

PMID- 23953122
TI  - Does ethnicity, gender or age of physiotherapy students affect performance in the
      final clinical placements? An exploratory study.
AB  - OBJECTIVES: To explore demographic differences in awarded marks of the final
      clinical placement in a physiotherapy undergraduate programme. DESIGN:
      Retrospective analysis of clinical placement assessment marks. SETTING: A London
      university offering clinical placements throughout South East England.
      PARTICIPANTS: 333 physiotherapy students entering physiotherapy training between
      2005 to 2009. MAIN OUTCOME MEASURES: Marks awarded following assessment using a
      clinical placement assessment form. RESULTS: The mean mark (SD) for age were
      standard entry 71 (7.4) vs. mature entry 72 (7.99) (ns); for gender male 72
      (8.45) vs. female 71 (7.21) (ns); and ethnicity White British 72 (7.71) vs.
      ethnic minority 70 (7.01) (p=0.023). No interaction effects were observed between
      the independent variables and only ethnicity demonstrated a statistically
      significant effect (mean difference (MD) 2.4% 95%CI 0.5 to 4.3, F=5.24, p=0.023).
      This difference was maintained in most subcategories. Significant differences
      were observed for the interpersonal section (MD 2.21% 95%CI 0.14 to 4.28,
      F=4.409, p=0.03), the clinical reasoning section (MD 2.39% 95%CI 0.53 to 4.25,
      F=6.37, p=0.012) and the treatment section (MD 2.93 95%CI 1.10 to 4.83, F=9.198,
      p=0.003). CONCLUSIONS: Physiotherapy students from minority ethnic backgrounds
      were awarded a significantly lower mark than their white majority peers in final
      clinical placements, although the difference was small. Potential reasons are
      considered, with the strongest recommendation being for further enquiry into the
      potential relationship between ethnicity and success in undergraduate
      physiotherapy education.

PMID- 23953123
TI  - The epigenetically-regulated miR-663 targets H-ras in K-562 cells.
AB  - miR-663 is a tumour suppressor that is potentially regulated by modification of
      CpG islands. Whether aberrant methylation is one of the reasons for miR-663 down
      regulation in some malignant cells and whether miR-663 targets oncogenes warrants
      further research. In the present study, we report that the CpG islands in the
      upstream region of pre-miR-663 are aberrantly methylated in the k-562 cell line
      and in the white blood cells of some chronic myelogenous leukaemia patients, and
      also that H-ras is one of the genes targeted by miR-663. Over-expression of miR
      663 may suppress proliferation of the k-562 cell line in part by enhancing cell
      apoptosis. 

PMID- 23953124
TI  - Genomic full-length sequence of two HLA-A alleles, A*30:01:01 and A*30:04:01,
      identified by cloning and sequencing.
AB  - Genomic full-length sequences of HLA-A*30:01:01 and A*30:04:01, were identified
      by cloning and sequencing from two Chinese donors. 

PMID- 23953125
TI  - New treatment possibilities for opioid-induced bowel dysfunction.

PMID- 23953126
TI  - The impact of daily arthritis pain on spouse sleep.
AB  - Although chronic pain has been linked to poorer psychosocial well-being in the
      spouse, the extent to which patient pain affects spouse sleep is unknown. The aim
      of the present study was to test the hypothesis that greater daily knee pain
      would be associated with poorer sleep for the spouse that evening. We also tested
      the hypothesis that this pain contagion is exacerbated in couples who have a
      close relationship. A total of 138 knee osteoarthritis (OA) patients and their
      spouses completed baseline interviews and a 22-day diary assessment. Multilevel
      lagged models indicated that greater knee OA pain at the end of the day was
      associated with spouses' poorer overall sleep quality that night and feeling less
      refreshed after sleep. In contrast, there was no evidence that spouse sleep was
      related to greater patient pain the next day. The effects of patient pain on
      spouse sleep were not due to disturbances in patient sleep and were also
      independent of spouse sex, depressive symptoms, and physical comorbidities; both
      partners' negative affect; and the quality of marital interactions throughout the
      day. As predicted, we also found that patient pain was more strongly related to
      less refreshing sleep for spouses who were in a close relationship. Findings
      illustrate that chronic pain may place the spouse's health at risk and suggest an
      important target for couple-oriented interventions. 

PMID- 23953128
TI  - Spatial memory and animal movement.
AB  - Memory is critical to understanding animal movement but has proven challenging to
      study. Advances in animal tracking technology, theoretical movement models and
      cognitive sciences have facilitated research in each of these fields, but also
      created a need for synthetic examination of the linkages between memory and
      animal movement. Here, we draw together research from several disciplines to
      understand the relationship between animal memory and movement processes. First,
      we frame the problem in terms of the characteristics, costs and benefits of
      memory as outlined in psychology and neuroscience. Next, we provide an overview
      of the theories and conceptual frameworks that have emerged from behavioural
      ecology and animal cognition. Third, we turn to movement ecology and summarise
      recent, rapid developments in the types and quantities of available movement
      data, and in the statistical measures applicable to such data. Fourth, we discuss
      the advantages and interrelationships of diverse modelling approaches that have
      been used to explore the memory-movement interface. Finally, we outline key
      research challenges for the memory and movement communities, focusing on data
      needs and mathematical and computational challenges. We conclude with a roadmap
      for future work in this area, outlining axes along which focused research should
      yield rapid progress. 

PMID- 23953130
TI  - A microalgae residue based carbon solid acid catalyst for biodiesel production.
AB  - Biodiesel production from microalgae is recognized as one of the best solutions
      to deal with the energy crisis issues. However, after the oil extraction from the
      microalgae, the microalgae residue was generally discarded or burned. Here a
      novel carbon-based solid acid catalyst derived from microalgae residue by in situ
      hydrothermal partially carbonization were synthesized. The obtained catalyst was
      characterized and subjected to both the esterification of oleic acid and
      transesterification of triglyceride to produce biodiesel. The catalyst showed
      high catalytic activity and can be regenerated while its activity can be well
      maintained after five cycles. 

PMID- 23953129
TI  - Effects of blockade of alpha4beta2 and alpha7 nicotinic acetylcholine receptors
      on cue-induced reinstatement of nicotine-seeking behaviour in rats.
AB  - Exposure to environmental stimuli conditioned to nicotine consumption critically
      contributes to the high relapse rates of tobacco smoking. Our previous work
      demonstrated that non-selective blockade of nicotinic acetylcholine receptors
      (nAChRs) reversed the cue-induced reinstatement of nicotine seeking, indicating a
      role for cholinergic neurotransmission in the mediation of the conditioned
      incentive properties of nicotine cues. The present study further examined the
      relative roles of the two major nAChR subtypes, alpha4beta2 and alpha7, in the
      cue-induced reinstatement of nicotine seeking. Male Sprague-Dawley rats were
      trained to intravenously self-administer nicotine (0.03 mg/kg/infusion, free
      base) on a fixed-ratio 5 schedule of reinforcement. A nicotine-conditioned cue
      was established by associating a sensory stimulus with each nicotine infusion.
      After nicotine-maintained responding was extinguished by withholding the nicotine
      infusion and its paired cue, reinstatement test sessions were conducted with re
      presentation of the cue but without the availability of nicotine. Thirty minutes
      before the tests, the rats were administered the alpha4beta2-selective antagonist
      dihydro-beta-erythroidine (DHbetaE) and alpha7-selective antagonist
      methyllycaconitine (MLA). Pretreatment with MLA, but not DHbetaE, significantly
      reduced the magnitude of the cue-induced reinstatement of responses on the
      active, previously nicotine-reinforced lever. In different sets of rats, MLA
      altered neither nicotine self-administration nor cue-induced reinstatement of
      food seeking. These results demonstrate that activation of alpha7 nAChRs
      participates in the mediation of the conditioned incentive properties of nicotine
      cues and suggest that alpha7 nAChRs may be a promising target for the development
      of medications for the prevention of cue-induced smoking relapse. 

PMID- 23953131
TI  - Next-generation sequencing reveals cryptic mtDNA diversity of Plasmodium relictum
      in the Hawaiian Islands.
AB  - Next-generation 454 sequencing techniques were used to re-examine diversity of
      mitochondrial cytochrome b lineages of avian malaria (Plasmodium relictum) in
      Hawaii. We document a minimum of 23 variant lineages of the parasite based on
      single nucleotide transitional changes, in addition to the previously reported
      single lineage (GRW4). A new, publicly available portal (Integroomer) was
      developed for initial parsing of 454 datasets. Mean variant prevalence and
      frequency was higher in low elevation Hawaii Amakihi (Hemignathus virens) with
      Avipoxvirus-like lesions (P = 0.001), suggesting that the variants may be
      biologically distinct. By contrast, variant prevalence and frequency did not
      differ significantly among mid-elevation Apapane (Himatione sanguinea) with or
      without lesions (P = 0.691). The low frequency and the lack of detection of
      variants independent of GRW4 suggest that multiple independent introductions of
      P. relictum to Hawaii are unlikely. Multiple variants may have been introduced in
      heteroplasmy with GRW4 or exist within the tandem repeat structure of the
      mitochondrial genome. The discovery of multiple mitochondrial lineages of P.
      relictum in Hawaii provides a measure of genetic diversity within a
      geographically isolated population of this parasite and suggests the origins and
      evolution of parasite diversity may be more complicated than previously
      recognized.

PMID- 23953132
TI  - Conversion of KEGG metabolic pathways to SBGN maps including automatic layout.
AB  - BACKGROUND: Biologists make frequent use of databases containing large and
      complex biological networks. One popular database is the Kyoto Encyclopedia of
      Genes and Genomes (KEGG) which uses its own graphical representation and manual
      layout for pathways. While some general drawing conventions exist for biological
      networks, arbitrary graphical representations are very common. Recently, a new
      standard has been established for displaying biological processes, the Systems
      Biology Graphical Notation (SBGN), which aims to unify the look of such maps.
      Ideally, online repositories such as KEGG would automatically provide networks in
      a variety of notations including SBGN. Unfortunately, this is non-trivial, since
      converting between notations may add, remove or otherwise alter map elements so
      that the existing layout cannot be simply reused. RESULTS: Here we describe a
      methodology for automatic translation of KEGG metabolic pathways into the SBGN
      format. We infer important properties of the KEGG layout and treat these as
      layout constraints that are maintained during the conversion to SBGN maps.
      CONCLUSIONS: This allows for the drawing and layout conventions of SBGN to be
      followed while creating maps that are still recognizably the original KEGG
      pathways. This article details the steps in this process and provides examples of
      the final result.

PMID- 23953134
TI  - Hodgkin lymphoma in Africa: present and future.
AB  - Hodgkin lymphoma (HL) was described for the first time in 1832 by Sir Thomas
      Hodgkin, who is considered the father of the disease. This lymphoma occupies a
      special place among childhood malignancies, due to its high rate of cure. HL is
      described as one of the most common haematological malignancies in African
      children. Despite high rates of survival achieved in resource rich countries, the
      outcome in Africa is not as rewarding as many challenges are encountered. This
      paper reviews published African studies on childhood HL in order to delineate the
      amplitude of this health problem and its African specifics, in the quest for
      effective ways to improve the outcome of the children diagnosed with this
      disease. 

PMID- 23953133
TI  - Rare coding variants of the adenosine A3 receptor are increased in autism: on the
      trail of the serotonin transporter regulome.
AB  - BACKGROUND: Rare genetic variation is an important class of autism spectrum
      disorder (ASD) risk factors and can implicate biological networks for
      investigation. Altered serotonin (5-HT) signaling has been implicated in ASD, and
      we and others have discovered multiple, rare, ASD-associated variants in the 5-HT
      transporter (SERT) gene leading to elevated 5-HT re-uptake and perturbed
      regulation. We hypothesized that loci encoding SERT regulators harbor variants
      that impact SERT function and/or regulation and therefore could contribute to ASD
      risk. The adenosine A3 receptor (A3AR) regulates SERT via protein kinase G (PKG)
      and other signaling pathways leading to enhanced SERT surface expression and
      catalytic activity. METHODS: To test our hypothesis, we asked whether rare
      variants in the A3AR gene (ADORA3) were increased in ASD cases vs. controls.
      Discovery sequencing in a case-control sample and subsequent analysis of
      comparison exome sequence data were conducted. We evaluated the functional impact
      of two variants from the discovery sample on A3AR signaling and SERT activity.
      RESULTS: Sequencing discovery showed an increase of rare coding variants in cases
      vs. controls (P=0.013). While comparison exome sequence data did not show a
      significant enrichment (P=0.071), combined analysis strengthened evidence for
      association (P=0.0025). Two variants discovered in ASD cases (Leu90Val and
      Val171Ile) lie in or near the ligand-binding pocket, and Leu90Val was enriched
      individually in cases (P=0.040). In vitro analysis of cells expressing Val90-A3AR
      revealed elevated basal cGMP levels compared with the wildtype receptor.
      Additionally, a specific A3AR agonist increased cGMP levels across the full time
      course studied in Val90-A3AR cells, compared to wildtype receptor. In Val90
      A3AR/SERT co-transfections, agonist stimulation elevated SERT activity over the
      wildtype receptor with delayed 5-HT uptake activity recovery. In contrast, Ile171
      A3AR was unable to support agonist stimulation of SERT. Although both Val90 and
      Ile171 were present in greater numbers in these ASD cases, segregation analysis
      in families showed incomplete penetrance, consistent with other rare ASD risk
      alleles. CONCLUSIONS: Our results validate the hypothesis that the SERT
      regulatory network harbors rare, functional variants that impact SERT activity
      and regulation in ASD, and encourages further investigation of this network for
      other variation that may impact ASD risk.

PMID- 23953135
TI  - On sitting and doing: ethnography as action in global health.
AB  - Contemporary discussions within the arenas of medical anthropology and global
      health are often restricted by the driving imperatives to "do something" about a
      particular health problem. Drawing on ethnographic fieldwork conducted in Nepal
      in 1997, which sought to follow the translation of AIDS prevention policies into
      local awareness, this paper addresses the need to revitalize theories of
      ethnography for an understanding of global health goals. The Nepal example
      underscores how the path toward decisions is never entirely clear, nor is it
      always obvious who benefits or loses from different approaches, even as public
      health discourse seeks to set a strict agenda around what the problem is and what
      should be done about it. Ethnography shows that definitions of what matters as
      well as understandings of why certain things matter are formulated from specific
      social locations. The paper therefore advocates for a practice of patient
      ethnographic "sitting" as a means to understanding, as a form of critical
      reflexivity, and as a diagnostic of the politics of relevance. 

PMID- 23953136
TI  - Smoking as an independent risk factor for severe skin reactions due to adjuvant
      radiotherapy for breast cancer.
AB  - Risk factors for severe acute radiation skin reactions (ARSR) have been described
      with conflicting results. The aim of this study was to identify risk factors for
      the development of severe ARSR in women undergoing adjuvant radiotherapy (RT) for
      breast cancer. 390 women were assessed at the first and final RT sessions and at
      followup. ARSR were measured by the Radiation Therapy Oncology Group/The
      Organization for Research and Treatment of Cancer, Acute Radiation Morbidity
      Scoring Criteria (RTOG/EORTC scale). Patients reported symptoms using visual
      analogue scale (VAS). Health related quality of life was assessed by EORTC QLQ
      C30 and sleep disturbances by the MOS-Sleep questionnaire. Clinical data included
      smoking status (carbon monoxide in expired air), body mass index (BMI) and
      treatment data. RT dose, >= 50 Gy (mean difference 1.9 CI: 1.0 to 3.5, p =
      0.040), high BMI (mean difference 4.3 CI: 2.2 to 8.3, p < 0.001) and smoking
      (mean difference 2.5 CI. 1.1 to 5.7, p = 0.027) were the factors strongest
      related to severe ARSR. Patients' with severe ARSR reported higher levels of pain
      and increased sleeping problems. To stop smoking during RT is the best decision
      patients can make to reduce the risk for severe ARSR since smoking is an
      independent risk factor.

PMID- 23953137
TI  - A novel link of HLA locus to the regulation of immunity and infection: NFKBIL1
      regulates alternative splicing of human immune-related genes and influenza virus
      M gene.
AB  - HLA locus contains immune-related genes and genetically regulates immune
      responses against both foreign- and self-antigens in humans. Inhibitor of kappaB
      like protein (IkappaBL), encoded by HLA-linked NFKBIL1, is a protein of unknown
      function, while genetic variations in NFKBIL1 are known to associate with the
      susceptibility to inflammatory and/or autoimmune diseases. In this study, we
      found that IkappaBL suppressed exon exclusion in alternative splicing of human
      immune-related genes such as CD45. Yeast-two-hybrid screening and
      immunoprecipitation assay revealed molecular association of IkappaBL with CLK1, a
      serine/threonine and tyrosine kinase, which plays a role in the alternative
      splicing. Unexpectedly, we found that the regulation of alternative splicing in
      CD45 by IkappaBL was independent from the kinase activity of CLK1. On the other
      hand, it was demonstrated that an SR protein, ASF/SF2, bound both IkappaBL and
      CLK1 at the RNA-recognition motifs of ASF/SF2, implying a competition of IkappaBL
      and CLK1 on SR protein. In addition, IkappaBL was found to regulate the CLK1
      dependent synthesis of M2 RNA, a splice variant of influenza A virus M gene.
      These observations suggest a functional involvement of IkappaBL in the regulation
      of alternative splicing in both human and viral genes, which is a novel link of
      HLA locus to the regulation of immunity and infection in humans.

PMID- 23953138
TI  - Removal of PCDD/Fs from contaminated sediment and released effluent gas by
      charcoal in a proposed cost-effective thermal treatment process.
AB  - A novel cost-effective thermal treatment technology has been proposed for the
      removal of PCDD/Fs from contaminated sediment and released effluent gas using
      charcoal as both an adsorbent and a thermal source. When a reactor was used for
      thermal treatment, the PCDD/Fs removal efficiency exceeded 98% from the sediment
      at the three different air superficial velocities employed in this study. The
      total PCDD/F international toxic equivalent (I-TEQ) contents, both in the treated
      sediments and effluent gas, were below the Japanese emission standard limit.
      Analysis of the PCDD/F contents in different fractions showed that large
      quantities of PCDDs but not PCDFs were evaporated from the sediment and adsorbed
      in the moist sediment column. This difference was attributed to the formation of
      PCDDs from pentachlorophenol (PCP) during the cooling process following the
      thermal treatment process in the reactor. This proposed thermal process provides
      a promising alternative to the conventional methods. 

PMID- 23953139
TI  - New type of [Bi6O6(OH)3](NO3)3.1.5H2O sheets photocatalyst with high
      photocatalytic activity on degradation of phenol.
AB  - A new type of [Bi6O6(OH)3](NO3)3.1.5H2O sheets photocatalyst was synthesized via
      a hydrothermal route. The photocatalytic properties were characterized by SEM,
      TEM, XRD and UV spectroscopy. It exhibited slightly better photocatalytic
      activity on phenol degradation than that of classic TiO2 P25 under UV
      illumination. Hydroquinone, catechol, resorcinol, and benzoquinone were
      identified as photodegradation intermediates. It has the advantages of high
      effective photodegradation efficiency and easy separation properties. 

PMID- 23953140
TI  - Allelic frequencies and statistical data from 30 INDEL loci in Uruguayan
      population.

PMID- 23953142
TI  - Comments on Gianelli et al. doi:10.1016/j.vetpar.2013.05.012 (2013) "Treatment of
      Dirofilaria repens microfilaraemia..." short communication.

PMID- 23953141
TI  - Out of sight but not gone: Sero-surveillance for cattle grubs, Hypoderma spp., in
      western Canada between 2008 and 2010.
AB  - Despite the lack of evidence of clinically infected cattle in western Canada
      since the late 1990s there is persistent evidence from serological sampling that
      warble fly infections remain endemic. As part of a general survey of cattle
      parasites conducted on calves entering a feedlot in southern Alberta sera were
      tested for the presence of anti-Hypoderma antibodies using an established ELISA.
      Calves for the study were drawn from auction markets in Manitoba, Saskatchewan,
      Alberta and British Columbia and serum samples were collected, according to a
      randomization scheme, as the calves entered a single feedlot in October through
      December (Survey) of three consecutive years (2008-2010). In addition, a sub
      sample of calves originating on a ranch in southeastern Alberta (Ranch 1) that
      had been the subject of previous surveillance was tested. Sero-prevalence of anti
      Hypoderma antibodies of the Survey calves ranged from 0.0% to 100.0% depending on
      origin and overall varied among the three years with the sero-prevalence being
      45.6%, 26.9%, 28.5% in 2008, 2009 and 2010 respectively. Sero-prevalence in Ranch
      1 calves varied among years, with one year being much higher and was different
      from overall Survey sero-prevalence in two of three years (31.7%, 64.1%, 38.5% in
      2008, 2009, 2010 respectively). In the Survey population there was a trend to
      lower sero-prevalence over the three years while on Ranch 1 there was no clear
      trend. In the samples with ELISA adjusted absorbance values above the positive
      cut-off an examination of the cumulative relative frequency showed that in all
      years approximately 90% of the samples were in the lower 3 of 14 bins in both
      populations and in two of three years in Ranch 1 population. The clustering of
      the positive ELISA data at the lower end of the range is suggestive of low level
      grub infestations. The increased frequency of high positive ELISA results from
      Ranch 1 in 2009 potentially indicate an 'outbreak year' in which pupal and adult
      fly survival was higher than for other years of this study resulting in more
      infested animals with higher burdens. Examination of precipitation and
      temperature profiles from the subject ranch support this suggestion. 

PMID- 23953143
TI  - Gastrointestinal nematode infection and performance of weaned stocker calves in
      response to anthelmintic control strategies.
AB  - Gastrointestinal nematode (GIN) parasite control recommendations are in a state
      of flux because of the increase in anthelmintic resistant cattle parasites, such
      as Cooperia spp. In addition, Cooperia spp. infection is typically high in warm
      season grass pastures and can affect growth performance of grazing stocker calves
      in the Gulf Coast Region. This study evaluated the effects of moxidectin pour-on,
      oxfendazole oral suspension, or a combination of the two given at separate times
      on infection and performance of weaned beef calves grazing summer forages. Steers
      (n=42) and heifers (n=31) were stratified by sex, d-11 fecal egg count (FEC), and
      d-1 shrunk body weight (BW) to one of 10 pastures with four anthelmintic
      treatments and one control. Treatments included: (1) oxfendazole given on d 0 and
      moxidectin on d 73 (O+M), (2) moxidectin given on d 0 and oxfendazole on d 73
      (M+O), (3) moxidectin given on d 0 (M), (4) oxfendazole given on d 0 (O) and (5)
      no anthelmintic given (CON). Calves grazed for d-110 beginning May 27th. Response
      variables were FEC (collected on d-11, 14, 31, 45, 59, 73, 87 and 108),
      coprocultures (evaluated for d 87 and 108), final shrunk BW, shrunk BW gain,
      average daily gain (ADG), and full BW gain (collected on d 31, 59, 73, 87, and
      108). Calves treated with either oxfendazole (O+M and O) or moxidectin (M+O and
      M) on d 0 had significantly lower (P<0.001) FEC than the CON calves on d 14, 31
      and 45. However, the M+O treated calves had significantly higher (P<0.001) FEC
      than both oxfendazole treated groups. In addition, calves treated with a second
      dewormer on d 73 (O+M and M+O) had significantly lower (P<0.001) FEC by d 87 than
      the CON or M treated calves. Shrunk BW gain and ADG were significantly greater
      (P=0.005) for the O+M compared to the M treated and CON calves, but comparable
      with the M+O and O treated calves, respectively. Coprocultures sampled on d 87
      and 108 for calves not receiving a second dewormer were predominantly Cooperia
      spp. and Ostertagia spp. On d 87, no larvae were recovered from the M+O treated
      calves, whereas the O+M treated calves had 94% Cooperia spp. and 3% Ostertagia
      spp. recovered. Providing a benzimidazole with a macrocyclic lactone given at two
      different periods may provide better GIN parasite control and improve animal
      gains for stocker calves grazing warm-season grass pastures. 

PMID- 23953145
TI  - Cystoisospora canis (Apicomplexa: Sarcocystidae): development of monozoic tissue
      cysts in human cells, demonstration of egress of zoites from tissue cysts, and
      demonstration of repeat monozoic tissue cyst formation by zoites.
AB  - Sporozoites of Cystoisospora canis penetrated and developed to monozoic tissue
      cysts in 4 human, 1 monkey, 1 bovine and 2 canine cell lines. No asexual division
      was documented although multiple infection of a single cell was observed.
      Examination of cultures using transmission electron microscopy demonstrated that
      they were monozoic tissue cysts and contained a single sporozoite. The appearance
      of monozoic tissue cysts in all cell lines was similar but the parasitophorous
      vacuole surrounding some sporozoites in DH82 dog macrophages was swollen.
      Monozoic tissue cysts were observed for up to 127 days in human pigmented retinal
      epithelial cells. Treatment of cell cultures containing monozoic tissue cysts
      with 0.75 sodium taurocholic acid and 0.25% trypsin stimulated egress of zoites
      (former sporozoites) from tissue cysts. Zoites collected from monozoic tissue
      cysts were able to penetrate and develop to monozoic tissue cysts in new host
      cells. Monozoic tissue cysts survived exposure to acid pepsin solution indicating
      that they would be orally infectious. The tissue cyst wall surrounding zoites did
      not autofluoresce as did oocyst and sporocyst walls exposed to UV light. We
      believe that C. canis can be used as a model system to study extra-intestinal
      monozoic tissue cysts stages of Cystoisospora belli of humans.

PMID- 23953144
TI  - Serological diagnosis of bovine neosporosis: a comparative study of commercially
      available ELISA tests.
AB  - Bovine neosporosis control programs are currently based on herd management and
      serodiagnosis because effective treatments and vaccines are unavailable. Although
      a wide variety of serological tools have been developed, enzyme-linked
      immunosorbent assays (ELISAs) are the most commonly commercialized tests. Partial
      comparative studies have been performed in the past, and the panel of available
      ELISAs has notably changed in the last few years. Therefore, diagnostic
      laboratories are requesting updated information about the performance of these
      tests. Accordingly, the aim of this study was to compare all of the commercially
      available ELISAs (n=10) by evaluating their performance and to re-standardize
      them based on TG-ROC analyses when necessary. For this purpose, a well
      characterized serum panel from experimentally and naturally infected bovines and
      non-infected bovines (n=458) was used. Two different definitions of gold standard
      were considered: (i) the result of the majority of tests and (ii) pre-test
      information based on epidemiological, clinical and serological data. Most of the
      tests displayed high sensitivity (Se) and specificity (Sp) values when both gold
      standard criteria were considered. Furthermore, all the tests showed near perfect
      agreement, with the exception of the pair-wise comparisons that included the VMRD
      and SVANOVIR. The best-adjusted ELISAs were the HIPRA-CIVTEST, IDVET, BIOVET and
      IDEXX Rum (Se and Sp>95%). After the TG-ROC analyses, higher Se and Sp values
      were obtained for the BIO-X, LSI Bov, LSI Rum and IDEXX Bov, though the increases
      were more significant for the SVANOVIR and VMRD. The Kappa values also increased
      with the new adjusted cut-offs. This is the first study that offers updated
      performance evaluations of commercially available ELISAs. Such analyses are
      essential for diagnostic laboratories and are valuable to the companies that
      develop and distribute these tests. 

PMID- 23953146
TI  - Periparturient transmission of Cryptosporidium xiaoi from ewes to lambs.
AB  - The mechanism for the maintenance of Cryptosporidium infection in sheep between
      yearly lambing periods is not clear. Previously, periparturient shedding of
      oocysts as the result of stress from lambing was suspected to be a mechanism for
      the initiation of Cryptosporidium infection in lambs, but this has never been
      verified by genotyping studies. In this study, fecal specimens from four age
      groups of sheep in Inner Mongolia, China were examined for Cryptosporidium spp.
      by PCR-restricted fragment length polymorphism and sequence analyses of the small
      subunit (SSU) rRNA gene, including 59 ewes 1 week before parturition, 154 ewes at
      parturition, 87 lambs of 3-4 weeks, and 75 lambs of 15-16 weeks. The
      Cryptosporidium infection rate in ewes at parturition (7.8%) was significantly
      higher than at 1 week before parturition (1.7%). Higher infection rates were
      found in lambs (18.4% and 26.7% for 3-4-week-old and 15-16-week-old lambs,
      respectively). Most (10/13) Cryptosporidium-positive ewes were shedding
      Cryptosporidium xiaoi, which was also the dominant species (15/16) in neonatal
      lambs of 3-4 weeks in age (15/16). The less common species in ewes,
      Cryptosporidium ubiquitum, was not found in lambs of 3-4 weeks but was the
      dominant species (14/20) in lambs of 15-16 weeks. The major zoonotic
      Cryptosporidium species, C. parvum (of the IIaA15G2R1 subtype), was only found in
      one lamb. These data support the occurrence of periparturient transmission of
      Cryptosporidium spp., especially C. xiaoi, from ewes to lambs.

PMID- 23953147
TI  - Immunological variation in Taenia solium porcine cysticercosis: measurement on
      the variation of the antibody immune response of naturally infected pigs against
      antigens extracted from their own cysticerci and from those of different pigs.
AB  - Although it is widely assumed that both antigen and host immunological
      variability are involved in the variable intensity of natural porcine infections
      by Taenia solium (T. solium) cysticercis and success of immunodiagnostic tests
      vaccines, the magnitude of such combined variability has not been studied or
      measured at all. In this paper we report statistical data on the variability of
      the antibody response of naturally infected pigs against the antigens extracted
      from the vesicular fluids of their own infecting cysts (variance within pigs) and
      against antigen samples extracted from cysts of other cysticercotic pigs
      (variance among pigs). The variation between pigs was greater than the inter-pigs
      variations, which suggests that a concomitant immunity process prevents the
      establishment of cysts coming from a subsequent challenge. In so doing, we found
      that there is not a single antigenic band that was recognized by all hosts and
      that antigens varied among the cysts within the same pigs as well as among pigs.
      Our results may be valuable for the improvement of immunodiagnostic tests and of
      effective vaccines against naturally acquired porcine T. solium cysticercosis. 

PMID- 23953148
TI  - Lack of efficacy of monepantel against Teladorsagia circumcincta and
      Trichostrongylus colubriformis.
AB  - After reports of the apparent failure of monepantel to reduce the egg counts of
      goats on a farm in the lower North Island of New Zealand, faecal egg count
      reduction tests were conducted in goats and lambs resident on the property, and a
      confirmatory, slaughter study was conducted using 12 sheep, sourced elsewhere,
      that were grazed on the farm for approximately 5 weeks. In the egg count
      reduction test in goats, 8 animals were given monepantel at 3.9 mg/kg (just over
      1.5* the sheep dose rate of 2.5mg/kg), whilst four received 7.7 mg/kg (just over
      3* the sheep dose). In the egg count reduction test in sheep, 15 lambs were
      treated with 3.0mg/kg of monepantel. For the confirmatory study, the sheep were
      housed indoors for 2 weeks before half were treated with 2.9 mg/kg monepantel and
      the animals were killed for worm counts 9 days later. There was no evidence of
      efficacy in either egg count reduction test, or in the goats, the two dose rates
      used appeared equally ineffective. Likewise, there were no significant reductions
      in egg counts or worm burdens in the slaughter study. Monepantel was ineffective
      against at least two gastrointestinal nematode species, Teladorsagia circumcincta
      and Trichostrongylus colubriformis. These findings represent the first report
      from the field of resistance having developed to the anthelmintic monepantel with
      severe resistance developing in more than one species after being administered on
      17 separate occasions to different stock classes and in less than 2 years of the
      product first being used on the farm in question.

PMID- 23953149
TI  - [The medical history taking in sexual health: skills and attitudes].
AB  - A sexual satisfactory life favourably affects quality of life, there being
      evidence that shows there are multiple organic processes of which sexual
      dysfunction is often a precocious sign of underlying organic disease
      (cardiovascular, endocrinological or neurological). Difficulties exist in
      recording the sexual anamnesis on the part of the professional, the patient, or
      by the health system. Nevertheless, given its importance, it is necessary for the
      doctor to adopt an attitude of active search, especially among the population of
      risk. To do this, it is necessary that the situation is propitious (sense of the
      opportunity), preserving the confidentiality of the meeting, and it will be
      carried out naturally and with empathy, adopting a listening attitude, taking
      into account the non-verbal language, without issuing valued judgments, and
      resorting to assertivity to overcome the resistances. This article proposes
      guidelines to perform an anamnesis adequately.

PMID- 23953150
TI  - Advancing advanced practice - clarifying the conceptual confusion.
AB  - BACKGROUND: In recent years, there has been a substantial increase in the number
      of nurses holding advanced practice nursing positions. However, the lack of
      clarity regarding key terms such as 'advanced practice nursing', 'advanced
      nursing practice', 'scope of practice' and 'extended practice', and international
      variability in how these terms are used has created significant confusion. This
      lack of clarity is problematic for nurses, other health professionals, health
      service consumers, educators and policy makers, particularly given the global
      mobility of the nursing workforce. OBJECTIVES: 1) To highlight the significant
      international variability in how advanced practice nursing, and associated terms
      such as extended and expanded practice, are defined and regulated across a
      variety of different English speaking countries, including the US, UK, New
      Zealand, Canada and Australia. 2) To propose innovative formulations for how the
      nursing profession may attempt to ensure greater precision and agreement around
      advanced practice terminology. DESIGN: Discursive paper. RESULTS: It was found
      that there is a considerable lack of clarity regarding the precise definitions of
      key terms surrounding the discussion of advanced practice. Additionally, there
      are large disparities in how the five chosen countries regulate advanced practice
      nursing, and roles such as that of the nurse practitioner. CONCLUSIONS: It is
      suggested that the confusion regarding advanced practice terminology can be
      reduced definitionally by minimising the use of the term 'expanded practice';
      defining advanced practice nursing to refer to the type of practice in defined
      and regulated advanced practice nursing scopes; and defining advanced nursing
      practice as expert practice within a regulated nursing scope.

PMID- 23953151
TI  - Authors may select immediate open access to their articles.

PMID- 23953152
TI  - Restricting topical ocular chloramphenicol eye drop use in the United States. Did
      we overreact?

PMID- 23953153
TI  - Clinical and molecular analysis of Stargardt disease with preserved foveal
      structure and function.
AB  - PURPOSE: To describe a cohort of patients with Stargardt disease who show a
      foveal-sparing phenotype. DESIGN: Retrospective case series. METHODS: The foveal
      sparing phenotype was defined as foveal preservation on autofluorescence imaging,
      despite a retinopathy otherwise consistent with Stargardt disease. Forty such
      individuals were ascertained and a full ophthalmic examination was undertaken.
      Following mutation screening of ABCA4, the molecular findings were compared with
      those of patients with Stargardt disease but no foveal sparing. RESULTS: The
      median age of onset and age at examination of 40 patients with the foveal-sparing
      phenotype were 43.5 and 46.5 years. The median logMAR visual acuity was 0.18.
      Twenty-two patients (22/40, 55%) had patchy parafoveal atrophy and flecks; 8
      (20%) had numerous flecks at the posterior pole without atrophy; 7 (17.5%) had
      mottled retinal pigment epithelial changes; 2 (5%) had multiple atrophic lesions,
      extending beyond the arcades; and 1 (2.5%) had a bull's-eye appearance. The
      median central foveal thickness assessed with spectral-domain optical coherence
      tomographic images was 183.0 MUm (n = 33), with outer retinal tubulation observed
      in 15 (45%). Twenty-two of 33 subjects (67%) had electrophysiological evidence of
      macular dysfunction without generalized retinal dysfunction. Disease-causing
      variants were found in 31 patients (31/40, 78%). There was a higher prevalence of
      the variant p.Arg2030Gln in the cohort with foveal sparing compared to the group
      with foveal atrophy (6.45% vs 1.07%). CONCLUSIONS: The distinct clinical and
      molecular characteristics of patients with the foveal-sparing phenotype are
      described. The presence of 2 distinct phenotypes of Stargardt disease (foveal
      sparing and foveal atrophy) suggests that there may be more than 1 disease
      mechanism in ABCA4 retinopathy.

PMID- 23953154
TI  - Ocular flora and their antibiotic resistance patterns in the midwest: a
      prospective study of patients undergoing cataract surgery.

PMID- 23953155
TI  - Short-term external buckling with pneumatic retinopexy for retinal detachment
      with inferior retinal breaks.

PMID- 23953156
TI  - Reply: To PMID 22995030.

PMID- 23953157
TI  - Reply: To PMID 23317649.

PMID- 23953158
TI  - Clinical and microbiological profile of post-penetrating keratoplasty infectious
      keratitis in failed and clear grafts.

PMID- 23953159
TI  - Reply: To PMID 23111174.

PMID- 23953160
TI  - Ultrasound biomicroscopy of the ciliary body in ocular/oculodermal melanocytosis.

PMID- 23953161
TI  - Reply: To PMID 23219068.

PMID- 23953162
TI  - Long-term risk of glaucoma after congenital cataract surgery.

PMID- 23953163
TI  - Reply: To PMID 23639132.

PMID- 23953164
TI  - Reply: To PMID 23398980.

PMID- 23953165
TI  - The effect of prior trabeculectomy on refractive outcomes of cataract surgery.

PMID- 23953166
TI  - Short-term trajectories of substance use in a sample of drug-involved
      probationers.
AB  - The current study estimates trajectories of illegal substance use in a sample of
      251 drug-involved probationers to identify risk profiles that predict group
      membership and explores the impact of treatment participation across these
      trajectories. Trajectory analyses reveal five patterns of drug use during
      probation supervision. Age and the use of hard drugs are identified as the
      strongest predictors of involvement in illicit drug use while on probation. The
      effect of participation in substance use treatment varies across treatment
      settings and trajectory groups. Prior research has tended to treat drug abusers
      as a homogeneous population, but the current study findings suggest considerable
      heterogeneity amongst drug users involved in the criminal justice system.
      Identifying trajectories of drug use during supervision can help identify
      individuals who may be more likely to persist in drug use, can inform practice by
      identifying individuals in need of more intensive treatment services, and can
      assist in developing new drug treatment strategies. 

PMID- 23953167
TI  - Predicting substance abuse treatment completion using a new scale based on the
      theory of planned behavior.
AB  - We examined whether a 9-item scale based on the theory of planned behavior (TPB)
      predicted substance abuse treatment completion. Data were collected at a public,
      outpatient program among clients initiating treatment (N=200). Baseline surveys
      included measures of treatment-related attitudes, norms, perceived control, and
      intention; discharge status was collected from program records. As expected, TPB
      attitude and control components independently predicted intention (model R
      squared=.56), and intention was positively associated with treatment completion
      even including clinical and demographic covariates (model R-squared=.24). TPB
      components were generally associated with the alternative readiness scales as
      expected, and the TPB remained predictive at higher levels of coercion.
      Meanwhile, none of the standard measures of readiness (e.g., the URICA and TREAT)
      or treatment coercion were positively associated with treatment participation.
      Results suggest promise for application of the TPB to treatment completion and
      support use of the intention component as a screener, though some refinements are
      suggested. 

PMID- 23953168
TI  - Beyond motivation: Initial validation of the commitment to sobriety scale.
AB  - From an addiction treatment and recovery standpoint maladaptive motivational
      hierarchies lie at the core of the challenge in mobilizing salutary behavior
      change. Motivation has been conceptualized as dynamic, interactive and
      modifiable, as well as multidimensional. Measures of recovery motivation have
      been developed and validated, but are generally only modest and variable
      predictors of future behavior. A related, but potentially more potent, construct,
      is that of commitment to sobriety as it denotes a clearer re-ranking of
      motivational hierarchies such that the recovery task is now given a top priority
      potentially less susceptible to the risks associated with undulating future
      circumstance. This study investigated the psychometric properties of a novel
      commitment to sobriety scale (CSS). Results revealed a coherent, psychometrically
      valid, and reliable tool that outperformed an existing commitment to abstinence
      scale (ATAQ; J. Morgenstern, R.M. Frey, B.S. McCrady, E. Labouvie, & C.J.
      Neighbors, 1996) and a gold standard measure of motivation (SOCRATES; W.R. Miller
      & J.S. Tonigan, 1996). This study highlights commitment to sobriety as an
      important addiction construct. Researchers and theoreticians may find the CSS
      useful in helping to explain how individuals achieve recovery, and practitioners
      may find clinical utility in the CSS in helping identify patients in need of more
      intensive or alternative intervention. 

PMID- 23953169
TI  - Differences in the acceptability of non-abstinence goals by type of drug among
      American substance abuse clinicians.
AB  - To assess whether acceptability of non-abstinence outcome goals varied depending
      on the specific drug a client consumes (alcohol, cannabis, amphetamine, heroin,
      cocaine, MDMA/ecstasy, polydrug), severity of diagnosis (DSM-IV Abuse vs.
      Dependence), and finality of outcome goal (intermediate vs. final), we recruited
      432 clinicians to complete a web-based questionnaire. More respondents rated non
      abstinence acceptable as an intermediate goal for clients diagnosed with alcohol
      abuse (44%) or cannabis abuse (43%) than for clients diagnosed as abusing the
      other listed drugs (23 to 31%). Similarly, larger proportions of respondents
      rated non-abstinence as acceptable as a final goal for clients diagnosed with
      alcohol abuse (30%) or cannabis abuse (24%) than for clients diagnosed as abusing
      the other drugs (11 to 13%). Only 9 to 13% of respondents rated non-abstinence as
      an acceptable final goal for clients diagnosed with dependence, but 20% to 30%
      rated non-abstinence as acceptable as an intermediate goal for clients diagnosed
      as dependent. 

PMID- 23953170
TI  - Cognitive behavioural therapy with behavioural analysis for pharmacological
      treatment-resistant chronic insomnia.
AB  - This study aimed to determine whether (1) cognitive behavioural therapy with
      behavioural analysis for insomnia (CBTi-BA) is more effective for insomnia and co
      morbid depressive symptoms than treatment as usual (TAU) and (2) whether CBTi-BA
      promotes earlier reduction of the daily dose of hypnotic medication in chronic
      insomnia resistant to pharmacological treatment. A total of 63 patients with
      chronic insomnia aged 20-77 years who already received hypnotic medication
      regularly were assigned to two interventions: combined therapy or TAU alone. The
      subjects provided demographic information and completed self-rating scales for
      insomnia and depressive symptoms. After treatment, the combined therapy group
      showed significant decreases in the symptoms of both insomnia and depression and
      significant reductions in the daily dose of hypnotic medication compared with the
      group receiving TAU alone. In the combined therapy group, 71% of the participants
      reported a reduction in insomnia to normal levels and 79% succeeded in decreasing
      the daily dose of hypnotics to 50% or less of the baseline dose. These results
      revealed that CBTi-BA can reduce insomnia and depressive symptoms as well as the
      daily dose of hypnotic medication in patients with chronic insomnia resistant to
      pharmacological treatment. 

PMID- 23953171
TI  - Pretreatment cortisol levels predict posttreatment outcomes among older adults
      with depression in cognitive behavioral therapy.
AB  - Previous studies suggest that individuals with elevated levels of cortisol (the
      "stress hormone") could be particularly resistant to treatment for depression.
      However, most of these studies have been conducted in the context of
      antidepressant medications, and no study has examined pretreatment cortisol
      levels as a predictor of treatment outcomes among older adults with depression in
      cognitive-behavioral therapy (CBT), despite the relevance of this population for
      such a research question. The current study includes 54 older adults with
      depression who provided salivary cortisol samples at baseline and completed
      measures of depression at pretreatment and posttreatment, following a 12-week
      course of CBT. Structural equation modeling results suggest that those with
      higher daily outputs of cortisol and flatter diurnal slopes were less likely to
      benefit from CBT-a finding which if replicated could have important implications
      for clinical practice and future research. 

PMID- 23953172
TI  - Prevalence of gastroesophageal reflux disease in major depressive disorder: a
      population-based study.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is a common physical disease
      among psychiatric patients. OBJECTIVE: We conducted this study to investigate the
      prevalence and risk of GERD in patients with major depressive disorder (MDD) in
      Taiwan. METHODS: We conducted a cross-sectional study using the National Health
      Insurance Research Database in Taiwan. The study subjects included 4790 patients
      with MDD and 728,749 people in the general population during 2005. Distributions
      of GERD as well as age, gender, income, region of residence, and medical
      comorbidities, such as diabetes mellitus, hypertension, renal disease,
      hyperlipidemia, and ischemic heart disease, in the 2 groups were examined by
      chi(2)-tests. Multivariate logistic regression models were used to analyze the
      associations between MDD and GERD. RESULTS: The 1-year prevalence rates of GERD
      in patients with MDD and the general population were 3.75% and 1.05%,
      respectively. The prevalence rate of GERD was significantly higher in patients
      with MDD in all age, sex, insurance amount, region, and urbanicity subgroups (all
      p < 0.001). The multivariate logistic regression analysis showed that patients
      with MDD were significantly associated with an increased rate for GERD ([Odds
      Ratio] = 3.16; 95% Confidence Interval = 2.71-3.68; p < 0.001). CONCLUSION: The
      prevalence of GERD was significantly higher in patients with MDD. In clinical
      practice, psychiatrists should pay attention to the possibility of GERD symptoms,
      such as heartburn, regurgitation, or dysphagia, and should consider consulting
      Gastroenterology specialists when clinically indicated.

PMID- 23953173
TI  - Functional neuroimaging correlates of medically unexplained vision loss.

PMID- 23953174
TI  - Short-term abstinence from cocaine self-administration, but not passive cocaine
      infusion, elevates alphaCaMKII autophosphorylation in the rat nucleus accumbens
      and medial prefrontal cortex.
AB  - Increases in alpha calcium/calmodulin-dependent protein kinase type II
      (alphaCaMKII) activity in the nucleus accumbens shell has been proposed as a core
      component in the motivation to self-administer cocaine and in priming-induced
      drug-seeking. Since cocaine withdrawal promotes drug-seeking, we hypothesized
      that abstinence from cocaine self-administration should enhance alphaCaMKII as
      well. We found that short-term abstinence from contingent, but not non
      contingent, cocaine i.v. self-administration (2 h/d for 14 d; 0.25 mg/0.1 ml, 6 s
      infusion) elevates alphaCaMKII autophosphorylation, but not the kinase
      expression, in a dynamic, time- and brain region-dependent manner. Increased
      alphaCaMKII autophosphorylation in the nucleus accumbens (NAc) and medial
      prefrontal cortex (mPFC), but not dorsolateral striatum (dlS), was found 24 h,
      but not immediately, after the last cocaine self-administration session. Notably,
      in the mPFC, but not NAc and dlS, alphaCaMKII autophosphorylation was still
      enhanced 7 d later. The persistent enhancement in the mPFC of abstinent rats may
      represent a previously unappreciated contribution to initial incubation of
      cocaine-seeking.

PMID- 23953175
TI  - The burden and correlates of hypertension in rural Ghana: a cross-sectional
      study.
AB  - AIM: Cardiovascular diseases (CVDs), of which hypertension is a major risk
      factor, are predicted to account for four times as many deaths as from
      communicable diseases by the year 2020. Hypertension, once rare, is rapidly
      becoming a major public health burden in sub-Saharan Africa (SSA). However, data
      on its prevalence, awareness, treatment and control are paltry, especially for
      rural communities. This study was done to determine the burden and correlates of
      adult hypertension in the rural Barekese sub-district of Ghana. METHODS: A cross
      sectional survey was conducted on 425 adults aged >= 35 in the Barekese sub
      district (estimated population 18,510). Socio-demographic characteristics,
      modifiable and non-modifiable risk factors, blood pressure (BP) and
      anthropometric measurements were collected using standardized protocols. RESULTS:
      Overall, the proportion of hypertension and isolated systolic hypertension is
      44.7% and 32.7% respectively in the study population. However, 64.9% of these
      were on treatment, with only 8.9% having controlled blood pressure (<140/90
      mmHg). The mean systolic and diastolic BP were 134.38 mmHg (standard deviation,
      SD: 21.46) and 84.32 mmHg (SD: 12.44). Obesity (Body Mass Index, BMI>30 kg/m2)
      was found in 37 (10.4% of the population), out of whom 7 (15.9%) were extremely
      obese (BMI> 40 kg/m2). Increasing age and level of education were positively
      correlated with increasing blood pressure. CONCLUSION: The high burden of
      hypertension in this population along with the considerable less detection,
      treatment and control is of great concern. There is the need to promote health
      education measures that will foster prevention and early detection of
      hypertension.

PMID- 23953176
TI  - Gonadal function in young adult males with metabolic syndrome.
AB  - AIMS: Aim of the study was to assess the gonadal function of young adult males
      with metabolic syndrome and to compare them with healthy age matched controls.
      METHODS: Forty young male subjects of age group 20-40 years who fulfilled the IDF
      criteria (2005) for diagnosis of metabolic syndrome were included in the study.
      Thorough evaluation of the subjects was done and history of sexual dysfunction if
      any was noted. Pooled blood samples were collected from each subject in fasting
      state for total testosterone, SHBG, FSH, LH, prolactin and insulin levels. All
      hormonal analyses were done by radio immune assay (RIA). Hypogonadism was defined
      as total testosterone less than 3ng/ml. Eighteen healthy age matched controls
      were also taken for the study. RESULTS: Twenty percent of subjects with metabolic
      syndrome had eugonadotropic hypogonadism compared to 5.5% controls. Subjects with
      metabolic syndrome also had significantly lower SHBG level compared to the
      controls. CONCLUSION: From this study it has been observed that eugonadotropic
      hypogonadism with low total testosterone and normal or low normal gonadotropin
      levels may be a feature of the metabolic syndrome in young adult males.
      Significant low SHBG levels as compared to controls could be one of the factors
      responsible for various biochemical alteration seen in these cases. This study
      highlights the importance of evaluating gonadal function in young adult males
      with the metabolic syndrome and has therapeutic implications in the management of
      such subjects with gonadal dysfunction.

PMID- 23953177
TI  - Evaluation of risk factors for cardiovascular diseases among Saudi diabetic
      patients attending primary health care service.
AB  - BACKGROUND: Cardiovascular disease is currently the primary cause of morbidity
      and mortality in patients with diabetes. For each risk factor present, the risk
      of cardiovascular death is about three times greater in people with diabetes than
      people without diabetes. OBJECTIVES: To determine the risk factors for
      cardiovascular disease among patients with type 2 diabetes. To stratify the
      patients into risk categories to develop coronary arteries disease (CAD) based on
      the British Joint Societies risk chart. To assess the awareness and
      implementation of the risk assessment charts by primary care physicians SUBJECT
      AND METHODS: Cross sectional study was designed. Sixty six (66 patients) diabetic
      patients were selected randomly by simple selection, from them 29 were males and
      37 were females. Patients' medical records were reviewed. The following
      parameters were detected; blood pressure, lipid profile, weight, height, smoking
      and degree of glycemic control. A questionnaire was designed and distributed to
      randomly selected physicians working in primary health care assessed their
      awareness and implementation of risk assessment charts was done. RESULTS:
      Uncontrolled diabetes was found to be the common risk factor followed by
      uncontrolled lipid profile, obesity, uncontrolled systolic blood pressure and
      smoking. Seven percent (7%) of male group felled in highest risk group in
      comparison with 1% in female group (P<0.05), while 31% in male group felled in
      mild risk group in comparison with 90% in female group (P<0.05). Sixty two
      percent (62%) in male group felled in high risk group in comparison with 9% in
      female group (P<0.05). Criteria for ranking in risk class differed between male
      and female group. Forty one physicians were contacted and received the
      questionnaire. Twenty nine (70.7%) physicians were responded to the
      questionnaire. Twenty two (22) informed that they were aware about risk
      assessment score systems. Fourteen (14) physicians informed that they were aware
      about the BJSs charts but only two informed that they had used it to assess their
      patients. CONCLUSION: Clustering of multi risk factors is a serious event which
      may raise the risk category of diabetic patients. For each risk category the risk
      factors may differed between male and female patients. More studies are
      recommended to study distribution of risk factors between male and female
      diabetic patients. Attention should be directed toward raising the awareness
      about the risk assessment scoring system and encouraging physicians to use it.

PMID- 23953178
TI  - Association of the six transmembrane protein of prostate 2 gene polymorphisms
      with metabolic syndrome in Han Chinese population.
AB  - AIM: The six-transmembrane protein of prostate 2 (STAMP2) has been demonstrated
      to play a potential role in the pathogenesis of metabolic syndrome (MetS). The
      present study was designed to investigate the association of STAMP2 gene
      polymorphisms with MetS in Han Chinese population. METHODS: A case-control study
      enrolled 350 Han Chinese subjects in two groups: 182 MetS patients and 168
      control subjects. The clinical and biochemical characteristics were determined.
      Three single nucleotide polymorphisms (SNPs), rs1981529, rs12386756 and
      rs10263111 in STAMP2 gene were genotyped. The association of STAMP2 gene
      polymorphisms with MetS was analyzed. RESULTS: SNPs rs1981529 and rs10263111 were
      found to be significantly associated with MetS phenotype in male population
      (P=0.014 and 0.025). Moreover, SNP rs1981529 was found to be associated with high
      density lipoprotein-cholesterol in male cases and with body mass index in female
      cases (P=0.014 and 0.049). SNP rs10263111 was found to be associated with both
      waist circumference and diastolic blood pressure in total cases (P=0.044 and
      0.033). Haplotype analysis yielded significant association of STAMP2 gene with
      MetS in total (global P=0.0109) and male population (global P=0.0004).
      CONCLUSION: Our findings revealed that STAMP2 gene polymorphisms are likely to
      significantly contribute to the risk of MetS in male Han Chinese population.

PMID- 23953179
TI  - One-year real-life efficacy of sitagliptin revealed importance of concomitant
      pioglitazone use in Japanese patients with type 2 diabetes mellitus.
AB  - AIMS: Dipeptidyl-peptidase 4 inhibitors have become one of the most popular
      antidiabetic drugs. However, what kind of combinations with other drugs were
      advantageous was not known. Here, we tried to elucidate it in a real-life
      clinical setting. METHODS: We retrospectively studied efficacies of sitagliptin
      in 87 Japanese patients with type 2 diabetes mellitus for 52 weeks. We divided
      subjects into excellent, effective and unresponsive subgroups according to
      glycemic responses to sitagliptin. RESULTS: In the excellent and effective groups
      the minimum HbA1c values were attained at 16 weeks while HbA1c levels in the
      unresponsive group kept increasing during the study period. There was a
      significant difference in the baseline HbA1c values between the excellent and
      unresponsive groups (p=0.02). Interestingly, the mean doses of pioglitazone were
      highest in the excellent group and lowest in the unresponsive group (p=0.02).
      When we compared the effective and unresponsive groups, the mean doses of
      sulfonylureas were constantly higher in the effective group than in the
      unresponsive group (p=0.05). CONCLUSIONS: These data suggest that the baseline
      HbA1c value can be a factor that predicts the extent of HbA1c reduction and
      reveal a possibility that the concomitant use of pioglitazone augments glycemic
      responsiveness to sitagliptin.

PMID- 23953180
TI  - 25-Hydroxyvitamin D [25(OH)D] levels and diabetic foot ulcer: is there any
      relationship?
AB  - AIMS: In recent years, there has been an effort to understand possible roles of
      25(OH)D, including its role in the immune system particularly on T cell medicated
      immunity, pancreatic insulin secretion and insulin action. 25(OH)D stimulates the
      cell differentiation and reduces cell proliferation, which is essential for cell
      growth and wound healing. However, data on the association between low level of
      plasma 25(OH)D and diabetic foot syndrome are scarce. MATERIALS AND METHODS:
      Circulating plasma levels of 25(OH)D were measured in diabetic patients with
      ulcer (n=162) and without ulcer (n=162) in a prospective cohort hospital based
      study. RESULTS: Of these patients, 85.1% had type 2 diabetes. Subjects with
      diabetic foot ulcer showed lower median plasma level of 25(OH)D [6.3(4.2-11.1) vs
      28.0(21.4-37.0)] ng/ml after adjusting the age and BMI. Regardless of the low
      levels of 25(OH)D in cases and controls, it was associated with neuropathy, sex
      (female), duration of ulcer healing, and smoking status and independent of
      confounding factors, including BMI (kg/m2), A1c (%), hypertension, nephropathy,
      foot ulcer, retinopathy, CAD, PAD, HDL-C (mg/dl) and LDL-C (mg/dl). The factors
      which predict the risk of developing ulcer independent of 25(OH)D status were A1c
      (>6.9%) [OR 4.37; RR 1.77], HDL-C (<40mg/dl) [OR 1.16; RR 1.07], LDL-C
      (>100mg/dl) [OR 1.07; RR 1.03], triglycerides (>200mg/dl) [OR 1.40; RR 1.19],
      neuropathy [OR 6.88; RR 3.12], retinopathy [OR 3.34; RR 1.91], hypertension [OR
      1.64; RR 1.28], nephropathy [OR 3.12; RR 1.87] and smoking [OR 4.53; RR 2.99]
      using odds and risk ratios. CONCLUSION: It is not clear whether the suppression
      of delayed wound healing seen during 25(OH)D deficiency is due to the secondary
      effect or is a direct action of vitamin D on certain components of the immune
      system. Long-term randomized trials are needed to see the impact of vitamin D
      supplementation on the outcome of diabetic foot patients.

PMID- 23953181
TI  - Metabolic syndrome and impaired health-related quality of life and in non
      Hispanic White, non-Hispanic Blacks and Mexican-American Adults.
AB  - OBJECTIVE: We examined the relationship between metabolic syndrome (MetS) and
      impaired health-related quality of life (HRQoL) in non-Hispanic Whites (NHW), non
      Hispanic Black (NHB), and Mexican-Americans (MA). METHODS: Data (n=5170) from
      2009-2010 NHANES were used. Subjects perceived poor overall health (POH), poor
      physical health (PPH), and poor mental health (PMH) status in the past 30 days
      were used as indices of impaired HRQoL. Race/ethnic-specific associations between
      MetS and indices of HRQoL were determined using prevalence odds ratios (POR) from
      logistic regression models. Statistical adjustments were made for age, sex,
      education, marital status, income and smoking. RESULTS: Rates of POH, PPH and PMH
      in the past 30 days increased linearly with increased number of components of
      MetS in NHW, NHB and MA. MetS was associated with increased odds of PPH in NHW
      (POR=2.34; 95% CI=1.73-3.17) and MA (POR=1.65; 95% CI=1.09-2.50); increased odds
      of PPH in NHW (POR=1.65; 95% CI=1.18-2.31), NHB (POR=1.83; 95% CI=1.01-3.35), and
      MA (POR=1.67; 95% CI=1.09-2.83); and increased odds of PMH in NHW (POR=1.50; 95%
      CI=1.08-2.08), NHB (POR=2.28; 95% CI=1.29-4.01), and MA (POR=1.44; 95% CI=0.80
      2.59). Upon adjustment for other independent variables, smoking and lack of
      education were found associated with increased odds of impaired HRQoL.
      CONCLUSIONS: MetS is associated with POH, PPH, and PMH in American adults. From
      clinical standpoint, this study further suggests that HRQoL should be considered
      in the management of subjects with MetS. Robust public health programs designed
      to reduce the prevalence of MetS may help in reducing impaired HRQoL, including
      POH, PPH, and PMH in American adults who have MetS.

PMID- 23953182
TI  - Gender differences in prediabetes and insulin resistance among 1356 obese
      children in Northern California.
AB  - AIMS: While it has been shown that there are gender differences in prediabetes
      and insulin resistance among adults, less is known about whether these
      differences exist in children. Obese children have elevated risk for developing
      metabolic dysfunction, and this analysis was conducted to compare obese boys and
      girls. METHODS: Biomarkers of prediabetes (IFG and HbA1c) and insulin resistance
      (HOMA-IR), were examined for 1356 obese children (2-19 years) who presented to a
      pediatric weight management clinic between 2008 and 2012. Gender differences were
      analyzed with multivariate logistic regression. RESULTS: Boys were more likely
      than girls to have IFG (adjusted OR: 1.68; CI: 1.06-2.65), but less likely to
      have elevated HOMA-IR (adjusted OR 0.71; CI: 0.52 -0.97). The female predominance
      of insulin resistance was present at younger ages than the male predominance of
      IFG. There were no gender differences with respect to HbA1c. Elevated HbA1c
      identified 20.7% of the sample as prediabetic whereas IFG identified 7.8%.
      CONCLUSIONS: Similar to findings in adults, obese children appear to exhibit more
      impaired fasting glucose among boys and a higher predominance of insulin
      resistance among girls. However, HbA1c identified a larger proportion of these
      high-risk, obese youth as prediabetic than IFG.

PMID- 23953183
TI  - Association of genetic variability in selected regions in visfatin (NAMPT) gene
      with anthropometric parameters and dietary composition in obese and non-obese
      Central-European population.
AB  - AIMS: Visfatin (NAMPT/PBEF) is a recently identified adipocytokine which harbors
      strong insulin-mimetic activity and was reported to be associated with obesity.
      However, nothing is known about whether visfatin is related to specific
      nutritional behavior which may result in obesity development. This is the first
      study focusing on genetic variability of the visfatin gene and its association
      with circulating visfatin, anthropometric parameters and dietary composition.
      MATERIALS AND METHODS: We analyzed a total of 11 exons and adjacent non-coding
      regions of the NAMPT gene in 20 extremely obese Czech individuals (mean BMI
      52.2+/-5.0 SD) using direct sequencing and a frequency of rs2302559 was
      established in the validation cohort of another 605 individuals with completed 7
      day food records and complex anthropometric measurements. Serum levels of
      visfatin, leptin and leptin-receptor were measured in all sequenced individuals
      and in part of the validation cohort. RESULTS: Three common polymorphisms were
      identified, two in non-coding regions (rs78411774 A/C, rs71564769 A/C) and one
      synonymous SNP in exon 7 (rs2302559 A/G). The rs2302559 showed significant
      correlation with visfatin serum level throughout the entire study cohort
      (p<0.001); there was a significant tendency toward higher visfatin levels in G
      allele carriers with GG homozygotes having the highest visfatin serum levels.
      Furthermore, a negative correlation was observed between visfatin and leptin
      serum level (p=0.01). No association between investigated SNPs and anthropometric
      parameters or native dietary composition was observed. CONCLUSION: This is the
      first study to demonstrate that the rs2302559 polymorphism in the PBEF gene is
      related to circulating levels of visfatin. As the SNP is synonymous, we
      hypothesize it might be linked to another SNP in the PBEF gene which controls
      visfatin serum levels.

PMID- 23953184
TI  - Diabetes awareness and diabetes risk reduction behaviors among attendance of
      primary healthcare centers.
AB  - AIMS: The aims of this study were to assess level of awareness about diabetes and
      the level of adoption of diabetes risk behaviors among adult attending primary
      healthcare centers. METHODS: A cross-sectional descriptive study was conducted
      using a self-administrated questionnaire. In addition to demographic information,
      the questionnaire contained questions on diabetes awareness related to diabetes
      definition, symptoms, risk factors, complications and management of diabetes as
      well as questions on diabetes risk reduction behaviors and sources of information
      on diabetes. The data was analyzed with independent t-test, Pearson's correlation
      coefficient, and ANOVA test. RESULTS: A total of 541 participants aged >= 18
      years were recruited. The mean score of diabetes awareness was 27.5/40 [SD=5.7].
      The participants performed best in symptoms section with a mean score of 6.3/8
      [SD=1.6], and worst in the risk factors section with a mean score of 3.6/6
      (SD=1.4). With respect to diabetes risk reduction behaviors the results showed
      that the highest mean score was for fat reduction 2.0/4 [SD=0.8]; and the lowest
      mean score was for weight control or losing 1.7/4 [SD=0.8]. CONCLUSIONS: The
      current study demonstrated that substantial numbers of adult Jordanian lack the
      sufficient awareness about diabetes to prevent and cope with the increasing
      prevalence of diabetes in Jordan. Also, it demonstrated that adoption of diabetes
      risk reduction behaviors was suboptimal. Raising public awareness of diabetes and
      diabetes risk reduction behaviors through population-based programs and mass
      media should be planned and implemented.

PMID- 23953185
TI  - An adult with late onset type 1 DM and abnormal thyroid profile: a variant of
      type 1.5 diabetes mellitus.

PMID- 23953186
TI  - Pharmacology of signaling pathways: in type 2 diabetes.

PMID- 23953187
TI  - The impact of an invasive plant changes over time.
AB  - Many exotic plant invaders pose a serious threat to native communities, but
      little is known about the dynamics of their impacts over time. In this study, we
      explored the impact of an invasive plant Heracleum mantegazzianum (giant hogweed)
      at 24 grassland sites invaded for different periods of time (from 11 to 48
      years). Native species' richness and productivity were initially reduced by
      hogweed invasion but tended to recover after ~30 years of hogweed residence at
      the sites. Hogweed cover declined over the whole period assessed. A complementary
      common garden experiment suggested that the dynamics observed in the field were
      due to a negative plant-soil feedback; hogweed survival and biomass, and its
      competitive ability were lower when growing in soil inocula collected from
      earlier-invaded grasslands. Our results provide evidence that the initial
      dominance of an invasive plant species and its negative impact can later be
      reversed by stabilising processes. 

PMID- 23953188
TI  - Molecular design of new aggrecanases-2 inhibitors.
AB  - Aggrecanases-2 is a very important potential drug target for the treatment of
      osteoarthritis. In this study, a series of known aggrecanases-2 inhibitors was
      analyzed by the technologies of three-dimensional quantitative structure-activity
      relationships (3D-QSAR) and molecular docking. Two 3D-QSAR models, which based on
      comparative molecular field analysis (CoMFA) and comparative molecular similarity
      analysis (CoMSIA) methods, were established. Molecular docking was employed to
      explore the details of the interaction between inhibitors and aggrecanases-2
      protein. According to the analyses for these models, several new potential
      inhibitors with higher activity predicted were designed, and were supported by
      the simulation of molecular docking. This work propose the fast and effective
      approach to design and prediction for new potential inhibitors, and the study of
      the interaction mechanism provide a better understanding for the inhibitors
      binding into the target protein, which will be useful for the structure-based
      drug design and modifications. 

PMID- 23953190
TI  - Discovery of novel (1S)-(-)-verbenone derivatives with anti-oxidant and anti
      ischemic effects.
AB  - A series of novel (1S)-(-)-verbenone derivatives was synthesized bearing a 4
      styryl scaffold. The synthesized compounds were tested for their anti-oxidant,
      anti-excitotoxic, and anti-ischemic activities. These derivatives significantly
      reduced oxygen-glucose deprivation-induced neuronal injury and N-methyl-D
      aspartic acid-evoked excitotoxicity in cortical neurons. Furthermore, compound 3f
      was identified as a potent anti-ischemic agent in an in vitro ischemic model,
      potentially due to the inhibition of N-methyl-D-aspartic acid-evoked
      excitotoxicity and oxidative/nitrosative stress.

PMID- 23953191
TI  - Design, synthesis and antitubercular evaluation of novel 2-substituted-3H
      benzofuro benzofurans via palladium-copper catalysed Sonagashira coupling
      reaction.
AB  - A series of novel natural product like 2-substiuted-3H-benzofurobenzofurans
      designed by molecular hybridization were synthesized in very good yields. The key
      reactions involved in the synthesis are iodination of 2-dibenzofuranol using
      iodine monochloride followed by palladium-copper catalyzed Sonagashira-coupling
      of 1-iododibenzofuran-2-ol with various alkyl and aryl acetylenes. Among the all
      10 new compounds screened for in vitro anti-mycobacterial activity against
      Mycobacterium tuberculosis H37Rv, 2-(4-methoxy-2-methyl phenyl)-3H-benzofuro[3,2
      e]benzofuran (7c) was found to be most active with MIC 3.12 MUg/mL and has shown
      lower cytotoxicity with good therapeutic index.

PMID- 23953189
TI  - Identification of potent, selective, CNS-targeted inverse agonists of the ghrelin
      receptor.
AB  - The optimization for selectivity and central receptor occupancy for a series of
      spirocyclic azetidine-piperidine inverse agonists of the ghrelin receptor is
      described. Decreased mAChR muscarinic M2 binding was achieved by use of a chiral
      indane in place of a substituted benzylic group. Compounds with desirable balance
      of human in vitro clearance and ex vivo central receptor occupancy were
      discovered by incorporation of heterocycles. Specifically, heteroaryl rings with
      nitrogen(s) vicinal to the indane linkage provided the most attractive overall
      properties. 

PMID- 23953192
TI  - Anticholinesterase insecticide action at the murine male reproductive system.
AB  - The present report describes for the first time that anticholinesterase type
      insecticides specifically inhibit the fatty acid amide hydrolase and/or
      monoacylglycerol lipase, as secondary target(s), in the murine male reproductive
      system (testis and epididymis cauda), thereby presumably being involved with
      spermatotoxicity such as deformity, underdevelopment, and reduced motility. 

PMID- 23953193
TI  - Identification, synthesis and evaluation of substituted benzofurazans as
      inhibitors of CREB-mediated gene transcription.
AB  - Cyclic-AMP response-element binding protein (CREB) is a stimulus-activated
      transcription factor. Its transcription activity requires its binding with CREB
      binding protein (CBP) after CREB is phosphorylated at Ser133. The domains
      involved for CREB-CBP interaction are kinase-inducible domain (KID) from CREB and
      KID-interacting domain (KIX) from CBP. Recent studies suggest that CREB is an
      attractive target for novel cancer therapeutics. To identify novel chemotypes as
      inhibitors of KIX-KID interaction, we screened the NCI-diversity set of compounds
      using a split renilla luciferase assay and identified 2-[(7
      nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio]pyridine 1-oxide (compound 1, NSC228155)
      as a potent inhibitor of KIX-KID interaction. However, compound 1 was not
      particularly selective against CREB-mediated gene transcription in living HEK
      293T cells. Further structure-activityrelationship studies identified 4-aniline
      substituted nitrobenzofurazans with improved selectivity. 

PMID- 23953194
TI  - Donor specificity and regioselectivity in Lipolase mediated acylations of methyl
      alpha-D-glucopyranoside by vinyl esters of phenolic acids and their analogues.
AB  - Methyl alpha-D-glucopyranoside as a model acceptor was acylated by several
      phenolic and non-phenolic vinyl esters using immobilised Lipolase. Donor
      specificity and regioselectivity of reaction were investigated. Conversion and
      rate of acylation by structurally varied donors indicates that the synthetic
      reactivity of Lipolase corresponds to the hydrolytic activity of feruloyl
      esterase type A. Lipolase exhibited remarkable regioselectivity for primary
      position of methyl alpha-D-glucopyranoside. The acylation occurred exclusively at
      6-O primary position when vinyl esters of phenolic acids (hydroxybenzoates,
      hydroxyphenylalkanoates and hydroxycinnamates) served as acyl donors (5-77%). In
      addition to the major 6-O-acyl products (52-79%), 2,6-di-O-acylated derivatives
      were isolated from reaction mixtures (2-13%) when non-phenolic donors were used
      (vinyl esters of fully methoxylated derivatives of phenolic acids, along with
      vinyl benzoates, cinnamates or some heterocyclic analogues).

PMID- 23953195
TI  - Synthesis and antiproliferative activities of quebecol and its analogs.
AB  - Simple and efficient synthesis of quebecol and a number of its analogs was
      accomplished in five steps. The synthesized compounds were evaluated for
      antiproliferative activities against human cervix adenocarcinoma (HeLa), human
      ovarian carcinoma (SK-OV-3), human colon carcinoma (HT-29), and human breast
      adenocarcinoma (MCF-7) cancer cell lines. Among all the compounds, 7c, 7d, 7f,
      and 8f exhibited antiproliferative activities against four tested cell lines with
      inhibition over 80% at 75 MUM after 72 h, whereas, compound 7b and 7g were more
      selective towards MCF-7 cell line. The IC50 values for compounds 7c, 7d, and 7f
      were 85.1 MUM, 78.7 MUM, and 80.6 MUM against MCF-7 cell line, respectively,
      showing slightly higher antiproliferative activtiy than the synthesized and
      isolated quebecol with an IC50 value of 104.2 MUM against MCF-7.

PMID- 23953196
TI  - Molecular docking studies of the interaction between propargylic enol ethers and
      human DNA topoisomerase IIalpha.
AB  - Having identified a novel human DNA topoisomerase IIalpha (TOP2) catalytic
      inhibitor from a small and structure-focused library of propargylic enol ethers,
      we decided to analyze if the chirality of these compounds plays a determinant
      role in their antiproliferative activity. In this study, we describe for the
      first time the synthesis of the corresponding enantiomers and the biological
      evaluation against a panel of representative human solid tumor cell lines.
      Experimental results show that chirality does not influence the reported
      antiproliferative activity of these compounds. Docking studies of corresponding
      enantiomers against TOP2 reinforce the finding that the biological effect is not
      chiral-dependent and that these family of compounds seem to act as TOP2 catalytic
      inhibitors. 

PMID- 23953198
TI  - Effect of sex sorting on stallion spermatozoa: Heterologous oocyte binding,
      tyrosine phosphorylation and acrosome reaction assay.
AB  - The interest on sex sorting by flow cytometry on the equine industry has been
      increasing over the years. In this work, three different tests were performed in
      order to evaluate the membrane status of sorted stallion spermatozoa: assessment
      of binding ability to porcine oocytes, evaluation of acrosome integrity after
      stimulation with A23187, and detection of tyrosine phosphorylation. These
      evaluations were made after incubation for 0h, 1.5h and 3h in a capacitating
      medium. Sorted stallion spermatozoa attached similarly to the porcine oocytes,
      when compared with control samples. Sorted spermatozoa were more prone to undergo
      acrosome reaction (P<0.05), at the beginning and after 1.5h and 3h of incubation,
      and also had higher tyrosine phosphorylation of the tail (P<0.001), only at the
      beginning of the incubation period. Apparently sex sorted stallion spermatozoa
      are in a more advanced status of membrane destabilization, which could be
      associated with capacitation, although similar binding ability to porcine oocytes
      is maintained. 

PMID- 23953199
TI  - Behavioural manipulation of insect hosts by Baculoviridae as a process of niche
      construction.
AB  - BACKGROUND: Niche construction has received increasing attention in recent years
      as a vital force in evolution and examples of niche construction have been
      identified in a wide variety of taxa, but viruses are conspicuously absent. In
      this study we explore how niche construction can lead to viruses engineering
      their hosts (including behavioural manipulation) with feedback on selective
      pressures for viral transmission and virulence. To illustrate this concept we
      focus on Baculoviridae, a family of invertebrate viruses that have evolved to
      modify the feeding behaviour of their lepidopteran hosts and liquefy their
      cadavers as part of the course of infection. RESULTS: We present a mathematical
      model showing how niche construction leads to feedback from the behavioural
      manipulation to the liquefaction of the host, linking the evolution of both of
      these traits, and show how this association arises from the action of niche
      construction. Model results show that niche construction is plausible in this
      system and delineates the conditions under which niche construction will occur.
      Niche construction in this system is also shown to be sensitive to parameter
      values that reflect ecological forces. CONCLUSIONS: Our model demonstrates that
      niche construction can be a potent force in viral evolution and can lead to the
      acquisition and maintenance of the behavioural manipulation and liquefaction
      traits in Baculoviridae via the niche constructing effects on the host. These
      results show the potential for niche construction theory to provide new insights
      into viral evolution.

PMID- 23953200
TI  - Raman spectroscopy and partial least squares analysis in discrimination of
      peripheral cells affected by Huntington's disease.
AB  - Huntington's disease (HD) is a neurodegenerative disorder caused by trinucleotide
      CAG (Cytosine-Adenine-Guanine) expansion on the Huntingtin gene (HTT) encoding
      for the Huntingtin protein (Htt). The protein has been linked in peripheral
      fibroblasts with dysregulation of cellular components which are part of lipid
      rafts in plasma membrane sub-domains. Therefore the analysis of the plasma
      membrane might be a useful diagnostic biomarker for the detection of the presence
      and possible onset of HD in readily accessible peripheral cells. Here Raman
      spectroscopy has been used with a chemometric approach in the form of Partial
      Least Square (PLS) for an initial corroboration that the plasma membrane is
      indeed a sub-cellular biomarker discriminator for HD identification. Observations
      were made in the spectral regions from 400 to 1800 cm(-1) and 2700 to 3200 cm(-1)
      with the former region displaying the most significant differences and peak
      displacement between plasma membranes extracted from HD and control fibroblast
      cells. The major differences in plasma membrane composition reside in sub
      cellular elements putatively associated to cholesterol, phospholipids (mainly
      phophatidylinositol) as well as proteins containing tyrosine. These findings are
      indicative of the plasma membrane as an amenable biomarker for HD for further in
      vitro research with possible applications in vivo models.

PMID- 23953197
TI  - A method for quantitative measurement of lumbar intervertebral disc structures:
      an intra- and inter-rater agreement and reliability study.
AB  - BACKGROUND: There is a shortage of agreement studies relevant for measuring
      changes over time in lumbar intervertebral disc structures. The objectives of
      this study were: 1) to develop a method for measurement of intervertebral disc
      height, anterior and posterior disc material and dural sac diameter using MRI, 2)
      to evaluate intra- and inter-rater agreement and reliability for the measurements
      included, and 3) to identify factors compromising agreement. METHODS:
      Measurements were performed on MRIs from 16 people with and 16 without lumbar
      disc herniation, purposefully chosen to represent all possible disc contours
      among participants in a general population study cohort. Using the new method,
      MRIs were measured twice by one rater and once by a second rater. Agreement on
      the sagittal start- and end-slice was evaluated using weighted Kappa. Length and
      volume measurements were conducted on available slices between intervertebral
      foramens, and cross-sectional areas (CSA) were calculated from length
      measurements and slice thickness. Results were reported as Bland and Altman's
      limits of agreement (LOA) and intraclass correlation coefficients (ICC). RESULTS:
      Weighted Kappa (Kw (95% CI)) for start- and end-slice were: intra-:
      0.82(0.60;0.97) & 0.71(0.43;0.93); inter-rater: 0.56(0.29;0.78) &
      0.60(0.35;0.81). For length measurements, LOA ranged from [-1.0;1.0] mm to [
      2.0;2.3] mm for intra-; and from [-1.1; 1.4] mm to [-2.6;2.0] mm for inter-rater.
      For volume measurements, LOA ranged from [-293;199] mm3 to [-582;382] mm3 for
      intra-, and from [-17;801] mm3 to [-450;713] mm3 for inter-rater. For CSAs, LOA
      ranged between [-21.3; 18.8] mm2 and [-31.2; 43.7] mm2 for intra-, and between [
      10.8; 16.4] mm2 and [-64.6; 27.1] mm2 for inter-rater. In general, LOA as a
      proportion of mean values gradually decreased with increasing size of the
      measured structures. Agreement was compromised by difficulties in identifying the
      vertebral corners, the anterior and posterior boundaries of the intervertebral
      disc and the dural sac posterior boundary. With two exceptions, ICCs were above
      0.81. CONCLUSIONS: Length measurements and calculated CSAs of disc morphology and
      dural sac diameter from MRIs showed acceptable intra- and inter-rater agreement
      and reliability. However, caution should be taken when measuring very small
      structures and defining anatomical landmarks.

PMID- 23953201
TI  - Fabrication and characterisation of high performance polypyrrole modified
      microarray sensor for ascorbic acid determination.
AB  - In this study, gold microelectrode array (Au/MEA) with electrode of 12 MUm
      diameter was fabricated by photolithography technique. Subsequently, polypyrrole
      (Ppy) modified gold microarrays sensor (Ppy/Au/MEA) was prepared by cyclic
      voltammetry technique. The deposition potential range and number of cycles were
      optimised in order to get optimum thickness of Ppy film. Scanning Electron
      Microscope and Atomic Force Microscope investigations reveal that Ppy coating
      formed at 3 cycles is porous with thickness of 1.5 MUm which exhibiting high
      catalytic current for ascorbic acid (AA) in square wave technique (SWV). In
      contrast to earlier sensors designs, these Ppy/Au/MEA sensors exhibits lower
      detection limit (LOD) of 10 nm towards AA at physiological conditions. It also
      exhibits enhanced sensitivity (2.5 mA cm(-2) mM(-1)) and long range of linear
      detection limit from 10 nm to 2.8 mM. In the same way, polypyrrole modified macro
      Au (Ppy/Au/MA) biosensor was also fabricated and its electro catalytic property
      towards AA was compared with that of Ppy/Au/MEA. The Ppy/Au/MA exhibits
      sensitivity of only 0.27 mA cm(-2) mM(-1), LOD of 5 MUM and linear range of 10
      MUM to 2.2mM. Hence, our investigations indicate that the Ppy/Au/MEA could serve
      as highly sensitive sensor for AA than any of the earlier designs. So, the
      Ppy/Au/MEA electrode was utilised for determination AA in a wide variety of real
      samples.

PMID- 23953202
TI  - Signal amplification strategy for sensitive immunoassay of prostate specific
      antigen (PSA) based on ferrocene incorporated polystyrene spheres.
AB  - A new kind of signal amplification strategy based on ferrocene (Fc) incorporated
      polystyrene spheres (PS-Fc) was proposed. The synthesized PS-Fc displayed narrow
      size distribution and good stability. PS-Fc was applied as label to develop
      immunosensors for prostate specific antigen (PSA) after the typical sandwich
      immunoreaction by linking anti-PSA antibody (Ab2) onto PS-Fc. After the
      fabrication of the immunosensor, tetrahydrofuran (THF) was dropped to dissolve PS
      and release the contained Fc for the following stripping voltammetric detection.
      PS-Fc as a new electrochemical label prevented the leakage of Fc and greatly
      amplified the immunosensor signal. In addition, the good biocompatibility of PS
      could maintain the bioactivity of the antibodies. The response current was linear
      to the logarithm of PSA concentration in the range from 0.01 ng mL(-1) to 20 ng
      mL(-1) with a detection limit of 1 pg mL(-1). The immunosensor results were
      validated through the detection of PSA in serum samples with satisfactory
      results.

PMID- 23953203
TI  - Sensitive monitoring of monoterpene metabolites in human urine using two-step
      derivatisation and positive chemical ionisation-tandem mass spectrometry.
AB  - A gas chromatographic-positive chemical ionisation-tandem mass spectrometric (GC
      PCI-MS/MS) method for the simultaneous determination of 10 oxidative metabolites
      of the monoterpenoid hydrocarbons alpha-pinene, (R)-limonene, and Delta(3)-carene
      ((+)-3-carene) in human urine was developed and tested for the monoterpene
      biomonitoring of the general population (n=36). The method involves enzymatic
      cleavage of the glucuronides followed by solid-supported liquid-liquid extraction
      and derivatisation using a two-step reaction with N,O-bis(trimethylsilyl)
      trifluoroacetamide and N-(trimethylsilyl)imidazole. The method proved to be both
      sensitive and reliable with detection limits ranging from 0.1 to 0.3 MUg L(-1).
      In contrast to the frequent and distinct quantities of (1S,2S,4R)-limonene-1,2
      diol, the (1R,2R,4R)-stereoisomer could not be detected. The expected metabolite
      of (+)-3-carene, 3-caren-10-ol was not detected in any of the samples. All other
      metabolites were detected in almost all urine samples. The procedure enables for
      the first time the analysis of trace levels of a broad spectrum of mono- and
      bicyclic monoterpenoid metabolites (alcohols, diols, and carboxylic acids) in
      human urine. This analytical procedure is a powerful tool for population studies
      as well as for the discovery of human metabolism and toxicokinetics of
      monoterpenes.

PMID- 23953204
TI  - Low-density magnetofluid dispersive liquid-liquid microextraction for the fast
      determination of organochlorine pesticides in water samples by GC-ECD.
AB  - A new micro-extraction technique named low-density magnetofluid dispersive liquid
      liquid microextraction (LMF-DMMLE) has been developed, which permits a wider
      range of solvents and can be combined with various detection methods. Comparing
      with the existing low density solvents micro-extraction methods, no special
      devices and complicated operations were required during the whole extraction
      process. Dispersion of the low-density magnetofluid into the aqueous sample is
      achieved by using vortex mixing, so disperser solvent was unnecessary. The
      extraction solvent was collected conveniently with an external magnetic field
      placed outside the extraction container after dispersing. Then, the magnetic
      nanoparticles were easily removed by adding precipitation reagent under the
      magnetic field. In order to evaluate the validity of this method, ten
      organochlorine pesticides (OCPs) were chosen as the analytes. Parameters
      influencing the extraction efficiency such as extraction solvents, volume of
      extraction solvents, extraction time, and ionic strength were investigated and
      optimized. Under the optimized conditions, this method showed high extraction
      efficiency with low limits of detection of 1.8-8.4 ng L(-1), good linearity in
      the range of 0.05-10.00 MUg L(-1) and the precisions were in the range of 1.3
      9.6% (RSD, n=5). Finally, this method was successfully applied in the
      determination of OCPs in real water samples.

PMID- 23953205
TI  - A new method for precise determination of iron, zinc and cadmium stable isotope
      ratios in seawater by double-spike mass spectrometry.
AB  - The study of Fe, Zn and Cd stable isotopes (delta(56)Fe, delta(66)Zn and
      delta(114)Cd) in seawater is a new field, which promises to elucidate the marine
      cycling of these bioactive trace metals. However, the analytical challenges posed
      by the low concentration of these metals in seawater has meant that previous
      studies have typically required large sample volumes, highly limiting data
      collection in the oceans. Here, we present the first simultaneous method for the
      determination of these three isotope systems in seawater, using Nobias PA-1
      chelating resin to extract metals from seawater, purification by anion exchange
      chromatography, and analysis by double spike MC-ICPMS. This method is designed
      for use on only a single litre of seawater and has blanks of 0.3, 0.06 and <0.03
      ng for Fe, Zn and Cd respectively, representing a 1-20 fold reduction in sample
      size and a 4-130 decrease in blank compared to previously reported methods. The
      procedure yields data with high precision for all three elements (typically 0.02
      0.20/00; 1sigma internal precision), allowing us to distinguish natural
      variability in the oceans, which spans 1-30/00 for all three isotope systems.
      Simultaneous extraction and purification of three metals makes this method ideal
      for high-resolution, large-scale endeavours such as the GEOTRACES program.

PMID- 23953207
TI  - Screening for exogenous androgen anabolic steroids in human hair by liquid
      chromatography/orbitrap-high resolution mass spectrometry.
AB  - A method for the screening of various anabolic steroids and their esters in human
      hair, based on liquid-chromatography-high resolution mass spectrometry using an
      Exactive benchtop Orbitrap mass spectrometer, has been set up and validated. This
      method involved methanolic incubation of 30 mg of hair and analysis of the
      relevant extract in HPLC using a C18 column. The mass detector, with nominal
      resolving power of 100,000, operated in full scan mode in APCI under positive
      ionization mode. Analytes were identified by exact mass, correspondence of
      isotopic cluster and retention times. The limits of detection obtained varied
      from 10 to 50 pg mg(-1), and limits of quantitation were 0.5 ng mg(-1) for all
      compounds. The method was linear for all analytes in the ranges from the LOQ to 6
      ng mg(-1), giving correlation coefficients >0.99 for all analytes. Also accuracy
      (intended as %E) and repeatability (%CV) were always lower than 15%. Specificity
      was assessed by analysing ten blank samples and fifteen samples from polidrug
      abusers. This method was applied to a real-life case, resulting in the
      identification of testosterone undecanoate in the hair of a suspect. The analyte
      identity was confirmed by the analysis of its in-source fragmentation and
      comparison to a certified standard. Thanks to the scan acquisition, this method
      also enables retrospective re-analysis of the acquired datafile in case a further
      analyte needs to be screened.

PMID- 23953206
TI  - Superoxide generated by pyrogallol reduces highly water-soluble tetrazolium salt
      to produce a soluble formazan: a simple assay for measuring superoxide anion
      radical scavenging activities of biological and abiological samples.
AB  - Superoxide anion radical (O2(-)) plays an important role in several human
      diseases. The xanthine/xanthine oxidase system is frequently utilized to produce
      O2(-). However, false positive results are easily got by using this system. The
      common spectrophotometric probes for O2(-) are nitroblue tetrazolium (NBT) and
      cytochrome c. Nevertheless, the application of NBT method is limited because of
      the water-insolubility of NBT formazan and the assay using cytochrome c lacks
      sensitivity and is not suitable for microplate measurement. We overcome these
      problems by using 1,2,3-trihydroxybenzene (pyrogallol) as O2(-)-generating system
      and a highly water-soluble tetrazolium salt, 2-(4-iodophenyl)-3-(4-nitrophenyl)-5
      (2,4-disulfophenyl)-2H-tetrazolium sodium salt (WST-1) which can be reduced by
      superoxide anion radical to a stable water-soluble formazan with a high
      absorbance at 450 nm. The method is simple, rapid and sensitive. Moreover, it can
      be adapted to microplate format. In this study, the O2(-) scavenging activities
      of superoxide dismutase (SOD), L-ascorbic acid, N-acetyl-L-cysteine (NAC),
      albumin from human serum, flavonoids and herbal extracts were assessed by using
      this method. Meanwhile, the activities of tissue homogenates and serum were
      determined by using this validated method. This method, applicable to tissue
      homogenates, serum and herbal extracts, proved to be efficient for measuring O2(
      ) scavenging activities of biological and abiological samples.

PMID- 23953208
TI  - Elemental analyses of soil and sediment fused with lithium borate using isotope
      dilution laser ablation-inductively coupled plasma-mass spectrometry.
AB  - Quantitative analysis using laser ablation inductively coupled plasma mass
      spectrometry (LA-ICP-MS) remains challenging primarily due to the lack of
      appropriate reference materials available for the wide variety of samples of
      interest and to elemental fractionation effects. Isotopic dilution mass
      spectrometry (IDMS) is becoming the methodology of choice to address these issues
      because the different isotopes of an element represent near-perfect internal
      standards. In this work, we investigated the lithium borate fusion of powdered
      solid samples, including soils, sediments, rock mine waste and a meteorite, as a
      strategy to homogenously distribute, i.e. equilibrate the elements and the added
      isotopically enriched standards. A comparison of this methodology using two
      pulsed laser ablation systems (ArF* excimer and Nd:YAG) with different
      wavelengths as well as two ICP-MS instruments (quadrupole and double-focusing
      sector field) was performed. Emphasis was put on using standard equipment to show
      the potential of the proposed strategy for its application in routine
      laboratories. Cr, Zn, Ba, Sr and Pb were successfully determined by LA-ICP-IDMS
      in six Standard Reference Materials (SRMs) representing different matrices of
      environmental interest. Experimental results showed the SRM fused glasses
      exhibited a low level of heterogeneity (intra- and inter-sample) for both natural
      abundance and isotopically enriched samples (RSD <3%, n=3, 1sigma). A good
      agreement between experimental results and the certified values was also
      observed. 

PMID- 23953209
TI  - N-acetylcysteine induced quenching of red fluorescent oligonucleotide-stabilized
      silver nanoclusters and the application in pharmaceutical detection.
AB  - In this work, we reported a new, simple and sensitive method for determination of
      N-acetylcysteine (NAC) based on quenching of the red fluorescence of
      oligonuleotide-protected silver nanoculsters (Ag NCs) with the quantum yield of
      68.3+/-0.3%. This method was successfully used for the assay of NAC granules
      presenting a linear range from 100 nM to 1200 nM (LOD of 50 nM) with minimal
      interferences from potential coexisting substances. It is for the first time that
      quenching performance of the thiol-containing compound was found to follow a non
      linear Stern-Volmer profile, indicative of a complicated quenching mechanism with
      static quenching dominating, in which DNA-template of Ag NCs was partly replaced
      by NAC, as elucidated by spectral investigations. This study extended the
      analytical application of silver nanoclusters as well as provided a more
      insightful understanding of the quenching mechanism of thiol-compounds on the
      fluorescence of Ag NCs.

PMID- 23953210
TI  - A label-free and signal-on supersandwich fluorescent platform for Hg2+ sensing.
AB  - A label-free supersandwich fluorescent assay was demonstrated for the first time
      by taking Hg(2+) as a detection candidate. The principle of the proposed
      supersandwich fluorescent platform is based on the formation of supersandwich
      structure by T-Hg(2+)-T coordination and the fluorescence enhancement of the
      intercalated Genefinder (GF) in double strand DNA (dsDNA). Such supersandwich
      fluorescent DNA sensor exhibits a linear range of 10-300 nM for the detection of
      Hg(2+), with a detection limit of 2.5 nM on the basis of the 3sigma/slope (sigma
      represents the standard deviation of the blank samples), which is well below the
      permit of the U.S. Environmental Protection Agency (<10 nM). The detection can be
      fulfilled in less than 10 min. The proposed mix-and-detect fluorescent platform
      exhibits excellent sensitivity, selectivity, and convenient manipulation. The
      assay was successfully used to detect Hg(2+) in the lake water samples, which
      suggested its potential in practical samples.

PMID- 23953211
TI  - Optical metal-organic framework sensor for selective discrimination of some toxic
      metal ions in water.
AB  - This paper reports the development of a facile and effective approach, based on
      the use of Zr-based metal-organic frameworks (UiO-66) sensor with micropores
      geometry, shape and particle morphology for the visual detection and removal of
      ultra-traces of some toxic metal ions such as Bi(III), Zn(II), Pb(II), Hg(II) and
      Cd(II). UiO-66 was used as selective carriers for accommodating hydrophobic
      chromophore probes such as dithizone (DZ) without coupling agent for sensitive
      and selective discrimination of trace level of toxic analytes. The developed UiO
      66 sensor was utilized for the detection of ultra-traces of some toxic metal ions
      with the naked eye. The new sensor displays high sensitivity and selectivity of a
      wide range of detectable metals analytes up to 10(-10) mol dm(-3) in solution, in
      a rapid analyte uptake response (seconds). The developed sensor is stable, cost
      effective, easy to prepare, and would be useful for rapid detection and removal
      of ultra-traces of toxic metal ions in water samples.

PMID- 23953212
TI  - Mercury assisted fluorescent supramolecular assembly of hexaphenylbenzene
      derivative for femtogram detection of picric acid.
AB  - Aggregates of hexaphenylbenzene derivatives 3, having pyrene groups form network
      of fluorescent nanofibres in presence of mercury ions. Further, fluorescent
      nanofibres of 3-Hg(2+) supramolecular ensemble exhibit sensitive and pronounced
      response towards the picric acid. In addition, the solution coated paper strips
      of 3-Hg(2+) supramolecular ensemble can detect picric acid in the range of 2.29
      fg/cm(2), thus, providing a simple, portable and low cost method for detection of
      picric acid in solution and in contact mode.

PMID- 23953213
TI  - Open-sandwich immunoassay for sensitive and broad-range detection of a shellfish
      toxin gonyautoxin.
AB  - At present, the analytical method for paralytic shellfish poisoning (PSP) toxins
      in shellfish is the mouse bioassay (MBA), which is an official method of the
      Association of Analytical Communities (AOAC [8]). However, the low sensitivity
      and concerns over the number of live animals required for testing have been cited
      as the major reason for seeking its replacement. In this report, we employed an
      open-sandwich immunoassay (OS-IA) to detect gonyautoxin (GTX2/3), a kind of PSP
      toxins. OS-IA, which utilizes the antigen-induced enhancement of antibody VH/VL
      interaction, can measure a small molecule antigen in a noncompetitive format.
      Hence it has a wider working range and shorter measurement time. We isolated anti
      GTX2/3 antibody gene from a hybridoma GT-13A by screening a Fab-displaying phage
      library. Then the vectors for OS-IA were constructed, and examined for antigen
      concentration-dependency of the VH/VL interaction by OS-ELISA. As a result, in
      each case, signal intensity increases notably in a wide concentration range (0.1
      to >1000 ng mL(-1)) of free GTX2/3, which was enough to cover its regulation
      value (80 MUg 100 g(-1)) in many countries. So OS-IA will be widely applicable to
      detect PSP toxins in shellfish meats and in drinking water.

PMID- 23953214
TI  - Effect of temperature gradients on single-strand conformation polymorphism
      analysis in a capillary electrophoresis system using Pluronic polymer matrix.
AB  - Capillary electrophoresis-single strand conformation polymorphism (CE-SSCP)
      analysis is a prominent bioseparation method based on the mobility diversity
      caused by sequence-induced conformational differences of single-stranded DNA. The
      use of Pluronic polymer matrix has opened up new opportunities for CE-SSCP,
      because it improved the resolution for various genetic analyses. However, there
      still exists a challenge in optimizing Pluronic-based CE-SSCP, because the
      physical properties of Pluronic solutions are sensitive to temperature,
      particularly near the gelation temperature, where the viscoelasticity of Pluronic
      F108 solutions sharply changes from that of a Newtonian fluid to a hydrogel upon
      heating. We have focused on a set of experiments to control the ambient
      temperature of the CE system with the aim of enhancing the reliability of the CE
      SSCP analysis by using the Applied Biosystems ABI 3130xl genetic analyzer with
      Pluronic F108 solution matrix. The ambient temperature control allowed us to vary
      the inlet and outlet portion of the capillary column, while the temperature of
      the column was kept at 35 degrees C. The resolution to separate 2 single-base
      pair-differing DNA fragments was significantly enhanced by changing the
      temperature from 19 to 30 degrees C. The viscoelastic properties of the F108
      solution matrix upon heating were also investigated by ex situ rheological
      experiments with an effort to reveal how the development of gels in Pluronic
      solutions affects the resolution of CE-SSCP. We found that the column inlet and
      outlet temperatures of the capillary column have to be controlled to optimize the
      resolution in CE-SSCP by using the Pluronic matrix. 

PMID- 23953215
TI  - Sleep bruxism and oromandibular myoclonus in rapid eye movement sleep behavior
      disorder: a preliminary report.
AB  - OBJECTIVE: We aimed to compare rhythmic masticatory muscle activity typical of
      sleep bruxism and oromandibular myoclonus (OMM) during rapid eye movement (REM)
      sleep in patients with idiopathic REM sleep behavior disorder (iRBD) and in
      Parkinson disease (PD) patients with RBD (PD-RBD). METHODS: Sleep polygraphic
      data were collected from 9 age-matched controls and 28 patients (mean+/-standard
      error of the mean, 66.0+/-1.7 y) with a clinical and sleep laboratory diagnosis
      of RBD. Patients were divided into two groups: 13 patients with iRBD and 15
      patients with PD-RBD. Rhythmic masticatory muscle activity, a marker of sleep
      bruxism, and OMM were scored blind to subject's diagnosis from jaw
      electromyographic recordings during sleep. RESULTS: The rhythmic masticatory
      muscle activity index was significantly higher during REM sleep in iRBD subjects
      compared to controls (P<.01) and was significantly higher during non-REM (NREM)
      sleep in both subject groups compared to controls (P < or = .03). A positive
      sleep laboratory diagnosis of sleep bruxism was made in 25% of all patients. In
      iRBD, patients had more OMM during REM sleep than controls (2.4 times higher;
      P=.01). CONCLUSION: In the presence of a high frequency of rhythmic masticatory
      muscle activity during REM sleep, RBD may be suspected and further neurologic
      assessment is recommended.

PMID- 23953216
TI  - Pilot study of intravenous nicotine effects on cognitive performance in
      schizophrenia.

PMID- 23953217
TI  - Antipsychotics and mortality in first-onset schizophrenia: prospective Finnish
      register study with 5-year follow-up.
AB  - OBJECTIVE: Our aim was to assess the impact of the most commonly used typical and
      atypical antipsychotics on mortality of patients with first-onset schizophrenia.
      METHOD: We conducted a nationwide, register-based, five-year follow-up study of
      all patients presenting with first-onset of schizophrenia between 1998 and 2003.
      Details of reimbursed medicines were obtained from the register of Social
      Insurance Institution. RESULTS: After adjusting for age, gender, comorbid
      physical diseases and patient group, the use of second generation antipsychotics
      (SGAs), especially clozapine, olanzapine and quetiapine, was associated with
      reduced risk of all-cause mortality in patients with schizophrenia, while
      clozapine associated with lower suicide risk. First generation antipsychotics
      (FGAs), specifically levomepromazine, thioridazine or clorprothixene, were
      associated with increased risk of all-cause mortality. The FGAs, particularly
      clorprothixene, were associated with decreased suicide mortality. An increased
      likelihood for cardiovascular deaths was found among users of levomepromazine. In
      antidepressants, the use of mirtazapine associated with increased risk of
      suicide. CONCLUSIONS: Differences exist between FGAs' and SGAs' use in relation
      to mortality. These differences remain even when the patient's physical illness
      are taken into account when prescribing antipsychotic medication.

PMID- 23953219
TI  - Echinococcus species from red foxes, corsac foxes, and wolves in Mongolia.
AB  - The small intestines of 420 wild canids (111 corsac foxes, 191 red foxes and 118
      wolves) from Mongolia, were examined for adult worms of the genus Echinococcus.
      The Mongolian genotype of Echinococcus multilocularis was found in fifteen red
      foxes and four wolves, whereas two genotypes (G6/7 and G10) of Echinococcus
      canadensis were found in two and three wolves, respectively. No adult
      Echinococcus worms were found in the corsac foxes examined. The genotypes of E.
      multilocularis and E. canadensis are discussed in terms of host specificity and
      distribution in Mongolia. The importance of wolves in the completion of the life
      cycle of Echinococcus spp. is also discussed.

PMID- 23953218
TI  - Toxoplasma gondii exposure affects neural processing speed as measured by
      acoustic startle latency in schizophrenia and controls.
AB  - The prevalence of Toxoplasma gondii (TOXO) infection in schizophrenia (SCZ) is
      elevated compared to controls (odds ratio=2.73). TOXO infection is associated
      with psychomotor slowing in rodents and non-psychiatric humans. Latency of the
      acoustic startle response, an index of neural processing speed, is the time it
      takes for a startling stimulus to elicit the reflexive response through a three
      synapse subcortical circuit. We report a significant slowing of latency in TOXO
      seropositive SCZ vs. seronegative SCZ, and in TOXO seropositive controls vs.
      seronegative controls. Latency was likewise slower in SCZ subjects than in
      controls. These findings indicate a slowing of neural processing speed with
      chronic TOXO infection; the slowest startle latency was seen in the TOXO
      seropositive SCZ group.

PMID- 23953220
TI  - Arthralgia and aromatase inhibitors.

PMID- 23953221
TI  - Successful treatment of Erdheim-Chester disease by interleukin-1 receptor
      antagonist protein.
AB  - Erdheim-Chester disease is a rare non-langerhans systemic histiocytosis of
      unknown origin, associated with bone diseases and severe visceral complications.
      Therapies have been disappointing. A recombinant form of interleukin-1 receptor
      antagonist (anakinra) has been used in a few cases when usual treatment fails. We
      report a new case of successfully interleukin-1 receptor antagonist treatment in
      Erdheim-Chester disease. 

PMID- 23953222
TI  - Does immunodepression induced by TNF antagonists promote atypical scabies?

PMID- 23953223
TI  - Identification of two novel CLCN7 gene mutations in three Chinese families with
      autosomal dominant osteopetrosis type II.

PMID- 23953224
TI  - Immune-mediated myopathy related to anti 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase antibodies as an emerging cause of necrotizing myopathy induced by
      statins.
AB  - Immune-mediated necrotizing myopathy (IMNM) associated with statin use and anti 3
      hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody is a new and
      emerging entity that supports a link between statin use and IMNM and raises the
      questions of distinct clinical phenotypes and treatment strategy. We describe the
      clinical and histopathological characteristics of a patient and discuss the
      spectrum of IMNM and statin-induced myopathies. A 65-year-old man was suffering
      from proximal muscle weakness and elevated CK levels, following exposure to
      statin therapy. The symptoms worsened despite discontinuation of the drug. At
      that point, no myositis-specific or -associated antibodies were detected.
      Malignancy screening did not reveal abnormalities. Muscle biopsy demonstrated a
      predominantly necrotizing myopathy with minimal lymphocytic infiltrates, MHC
      class I expression in necrotic muscle fibers, and complement deposition on
      scattered non-necrotic muscle fibers. Muscle protein analysis by western blot was
      normal. The patient did not improve with steroid and methotrexate and required
      monthly intravenous immunoglobulin (IVIG) therapy. Muscle strength gradually
      improved, CK levels normalized and IVIG were stopped 1 year later. Screening for
      anti-HMGCR antibodies, not available at the time of presentation, was highly
      positive. Identification of anti-HMGCR antibodies in statin-exposed patients with
      myopathy appears to be helpful both for differential diagnosis and for treatment
      strategy. In patients who did not improve after discontinuation of the statin
      treatment, a muscle biopsy should be performed as well as screening for anti
      HMGCR antibodies. Patients with this disorder require aggressive
      immunosuppressive treatment.

PMID- 23953225
TI  - Long-term systemic glucocorticoid therapy: patients' representations,
      prescribers' perceptions, and treatment adherence.
AB  - INTRODUCTION: Glucocorticoids have been used since 1948 for their anti
      inflammatory and structural effects in various inflammatory diseases. The optimal
      use of glucocorticoids remains controversial. Patients may have a number of
      concerns about the effects of glucocorticoids. Many factors can adversely affect
      treatment adherence. OBJECTIVES: To evaluate the main adverse effects reported by
      patients and physicians, and to assess representations associated with
      glucocorticoid therapy and the underlying disease, via measurements of treatment
      adherence, with the goal of optimizing treatment strategies and improving patient
      information. METHODS: From December 2011 to May 2012, we conducted two surveys in
      125 patients receiving long-term glucocorticoid therapy and followed-up at the
      rheumatology department of the teaching hospital in Casablanca, Morocco, and in
      85 hospital physicians in various specialties, respectively. RESULTS: Mean
      glucocorticoid therapy duration was 6 years, mean maximal prescribed dosage was
      44.87 mg/d, and 50.4% of the patients had inflammatory joint disease. Adverse
      neuropsychiatric effects were reported by 70 out of 125 (56%) patients. Weight
      gain was the adverse effect deemed most bothersome by the physicians, who
      significantly underestimated the occurrence of neuropsychiatric adverse effects
      (27% vs 56%, P=0.034). Adherence was poor in 80 out of 125 (64%) patients, and 22
      out of 125 (18%) patients reported episodes of treatment discontinuation.
      CONCLUSION: Prescribers underestimate the frequency of neuropsychiatric adverse
      effects of long-term systemic glucocorticoid therapy. Regular follow-up visits
      during treatment, with collection of systemic adverse effects might improve
      treatment adherence.

PMID- 23953226
TI  - Hair-cycle changes in two patients taking tocilizumab.

PMID- 23953227
TI  - Decreased roundabout 1 expression promotes development of intrahepatic
      cholangiocarcinoma.
AB  - Roundabout 1 (Robo1) is a transmembrane receptor of the immunoglobulin family.
      Slit2 is one of its ligands. The function of Slit2/Robo1 signaling in the
      development of intrahepatic cholangiocarcinoma (ICC) remains to be elucidated. We
      examined the immunohistochemical expression of Robo1 and Slit2 and their
      clinicopathologic implications in 132 cases of ICC. Also, small interfering RNA
      of Robo1 was transfected into a high-expression ICC cell line, and a Robo1 vector
      was transfected into a low-Robo1 expression ICC cell line. The effect of Robo1
      suppression and overexpression in cell proliferation and migration of cultured
      ICC cells with Slit2 stimulation was investigated. Immunohistochemical study of
      ICC in the low-Robo1 expression group showed larger tumors (P = .015), a higher
      Ki-67 labeling index (P = .021), and low expression of Slit2 (P = .0005). The low
      Slit2 expression group frequently showed perineural invasion (P = .036) and lymph
      node metastases (P = .013). Low Robo1 expression was associated with a poor
      prognosis (P = .0207). Robo1 suppression in Huh28 cells tended to promote cell
      proliferation and migration, whereas Robo1 overexpression in RBE cells
      significantly suppressed cell proliferation and migration. Low Robo1 expression
      was associated with cell proliferation and migration in ICC and was one of the
      adverse prognostic factors in patients with these tumors. 

PMID- 23953228
TI  - Dysregulation of the mammalian target of rapamycin pathway in chromophobe renal
      cell carcinomas.
AB  - Targeted therapy in advanced clear cell renal cell carcinomas (RCC) is now an
      established modality. The latter is in stark contrast to non-clear cell subtypes.
      We explored the translational support for the use of antagonists of the mammalian
      target of rapamycin (mTOR) and the vascular endothelial growth factor pathways in
      chromophobe RCC. The immunoexpression of PTEN, phos-AKT, phosphorylated S6 (phos
      S6), 4EBP1, p27, c-MYC, and HIF-1alpha was evaluated in 33 patients with
      chromophobe RCC who were treated by partial/radical nephrectomy without adjuvant
      therapy. PTEN was lower in tumor than in normal kidney (P<.001), and loss of PTEN
      expression was found in 67% of the tumors. In tumor tissues, phos-S6 and 4EBP1
      were higher than in normal kidney (P<=.005). Conversely, scores of p27 were lower
      in tumor than in normal kidney (P<.001). Finally, scores of phos-AKT, c-MYC, and
      HIF-1alpha were not significantly different in tumor and in normal kidney.
      Overall mortality and cancer-specific mortality were 9% and 0%, respectively.
      Multifocal tumors had higher levels of PTEN, phos-AKT, and HIF-1alpha (P<=.01).
      None of the clinicopathologic variables (age, ethnicity, gender, pT stage, tumor
      size, multifocality, and positive surgical margins) was associated with outcome.
      Similarly, none of the tested biomarkers predicted overall mortality, either in
      unadjusted or adjusted Cox regression models. In summary, our study provides new
      evidence of dysregulation of the mTOR pathway in chromophobe RCC.
      Immunohistochemistry for mTOR pathway and hypoxia-induced pathway members lacked
      prognostic significance in our cohort. 

PMID- 23953229
TI  - Clinical cues for detection of people with undiscovered depression in primary
      health care: a case-control study.
AB  - AIM: To identify clinical cues indicative of depression in medical records of
      cases in primary care with undetected depression. BACKGROUND: Depressive
      disorders are common; the lifetime risk for men and women is 27% and 45%,
      respectively. Despite effective treatment methods such as antidepressants and
      cognitive behavioural therapy, depression often remains undiscovered in primary
      care, with great implications both on the individual and societal level. METHODS:
      Clinical cues indicating depression were sought in medical records the year
      before an opportunistic screening for depression in primary care. In a previous
      study of 221 patients in the waiting room of a primary care centre during 10
      randomly selected days, 45 (20%) showed signs of depression (MADRS-S ? 12) and
      60% of these were verified as having depressive disorders (Prime-MD). These 45
      patients constitute the cases in the present study. Age- and gender-matched
      controls were selected among those who scored below the chosen cut-off level.
      FINDINGS: Seventeen (38%) of the 45 cases compared with eight (18%) of the 45
      controls had one or more cues [odds ratio (OR) 2.81; 95% confidence interval
      (CI): 1.06-7.43]. Sleep disturbance showed the greatest difference between cases
      and controls (OR 4.53; 95% CI: 1.17-17.55). A significant relationship was found
      between severity of depression, frequency of cues and lower functional level.
      Cues were twice as common in patients with undetected depression and their
      functional level was lower. A two-stage procedure, screening and a structured
      diagnostic interview, is recommended when sleep disturbances and lowered function
      are present.

PMID- 23953231
TI  - Diffusion-weighted magnetic resonance for prediction of response after
      neoadjuvant chemoradiation therapy for locally advanced rectal cancer:
      preliminary results of a monoinstitutional prospective study.
AB  - PURPOSE: To evaluate diffusion-weighted imaging (DWI) for assessment of treatment
      response in locally advanced rectal cancer (LARC) 8 weeks after neoadjuvant
      chemoradiotherapy (CRT). METHODS AND MATERIALS: A total of 28 patients with LARC
      underwent magnetic resonance imaging (MRI) prior to and 8 weeks after CRT. Tumor
      volume (TV) was calculated on T2-weighted MRI scans as well as the apparent
      diffusion coefficient (ADC) was calculated using Echo-planar DWI-sequences. All
      data were correlated to surgical results and histopathologic tumor regression
      grade (TRG), according to Mandard's classification. Post-treatment difference ADC
      (%DeltaADC) and TV (%DeltaTV) changes at 8 weeks were compared complete response
      (CR; TRG1) and non-complete response tumors (non-CR; TRG2-5). RESULTS: The mean %
      ADC increase of CR group was significantly higher compared to non-CR group (77.2
      +/- 54.63% vs. 36.0 +/- 29.44%; p = 0.05). Conversely, the mean % TV reduction
      did not significantly differ in CR group from non-CR group (73.7% vs. 63.77%; p =
      0.21). Accordingly, the diagnostic accuracy of the mean % ADC increase to
      discriminate CR from non-CR group was significantly higher than that of the mean
      % TV reduction (0.913 vs. 0.658; p = 0.022). No correlation was found between
      mean % TV reduction and TRG (rho = 0.22; p = 0.3037), whereas a negative
      correlation between mean % ADC increase and TRG was recorded (r = -0.69; p =
      0.006). CONCLUSION: The mean % ADC increase appears to be a reliable tool to
      differentiate CR from non-CR after CRT in patients with LARC.

PMID- 23953230
TI  - Epigenetics of human papillomaviruses.
AB  - Human papilllomaviruses (HPVs) are common human pathogens that infect cutaneous
      or mucosal epithelia in which they cause warts, self-contained benign lesions
      that commonly regress. The HPV life cycle is intricately tied to the
      differentiation of the host epithelium it infects. Mucosotropic HPVs are the most
      common sexually transmitted pathogen known to mankind. A subset of the
      mucosotropic HPVs, so-called high risk HPVs, is etiologically associated with
      numerous cancers of the anogenital tract, most notably the cervix, as well as a
      growing fraction of head and neck cancers. In these cancers, the HPV genome,
      which normally exists an a double stranded, circular, nuclear plasmid, is
      commonly found integrated into the host genome and expresses two viral oncogenes,
      E6 and E7, that are implicated in the development and maintainance of the cancers
      caused by these high risk HPVs. Numerous studies, primarily on the high risk
      HPV16, have documented that the methylation status of the viral genome changes
      not only in the context of the viral life cycle but also in the context of the
      progressive neoplastic disease that culminates in cancer. In this article, we
      summarize the knowledge gained from those studies. We also provide the first
      analysis of available ChIP-seq data on the occupancy of both epigentically
      modified histones as well as transcription factors on the high risk HPV18 genome
      in the context of HeLa cells, a cervical cancer-derived cell line that has been
      the subject of extensive analyses using this technique. 

PMID- 23953232
TI  - Preoperative sexual function in women with rectal cancer.
AB  - BACKGROUND: Even though sexual dysfunction has been reported after rectal cancer
      treatment, information on preoperative sexual function is scarce, particularly in
      female patients. AIMS: To describe preoperative sexual function in women with
      rectal cancer, and to analyse potential sources of bias. METHODS: The Female
      Sexual Function Index (FSFI) was administered to women with newly diagnosed non
      metastatic rectal cancer, irrespective of whether they were sexually active or
      not. FSFI total and domain scores were calculated for women with complete
      responses to the corresponding items. Data were compared for those who did and
      did not complete all the FSFI domains, and for women in the study cohort, and
      those who were eligible for inclusion but not included. RESULTS: Sexual
      inactivity was common. Mean FSFI total score was low (16.4 +/- 10.6 SD) among the
      women who completed all six FSFI domains. The proportion of women who had a
      partner was higher in this group compared with those who did not complete all the
      domains (49 of 57 vs 7 of 25, p < 0.001). Eighty-two of the 157 women eligible
      for inclusion were included. Included women were younger (p = 0.002) and had less
      co-morbidity than those who were not included (p = 0.025). CONCLUSIONS: The low
      FSFI total score indicates sexual dysfunction. However, the use of FSFI in both
      women who are and who are not sexually active complicates interpretation of the
      data and may result in an information bias hampering internal validity. External
      validity may be limited by selection bias.

PMID- 23953233
TI  - EUS-guided biliary drainage by using a hepatogastrostomy approach.

PMID- 23953234
TI  - In vivo observation of aberrant innermost longitudinal muscle bundles in front of
      the circular muscle layer at the level of the esophagogastric junction during
      peroral endoscopic myotomy.

PMID- 23953235
TI  - Phosphoinositide 3-kinases as accelerators and brakes of autophagy.
AB  - Degradation of cytoplasmic material by autophagy plays a key role in protein
      homeostasis and metabolic control, as well as in the removal of intracellular
      protein aggregates, pathogens and damaged organelles. The concept of up- or down
      regulating this pathway pharmacologically in neurodegenerative diseases,
      infections, inflammation and cancer is therefore attractive. Among the key
      pharmacological targets in regulation of autophagy are the phosphoinositide 3
      kinases (PI3Ks), which mediate the phosphorylation of phosphatidylinositol
      (PtdIns) or PtdIns 4,5-bisphosphate in the 3-position of the (phospho)inositol
      headgroup. The catalytic products, PtdIns 3-phosphate (PtdIns3P) and PtdIns 3,4,5
      trisphosphate [PtdIns(3,4,5)P3 ], respectively, have opposing roles in autophagy.
      PtdIns3P, the product of class II and III PI3Ks, mediates the recruitment of
      specific autophagic effectors to the sites of origin of autophagic membranes and
      thereby plays an essential role in canonical autophagy. By contrast,
      PtdIns(3,4,5)P3 , the product of class I PI3Ks, triggers the target of rapamycin
      signalling pathway, which inhibits autophagy. In this review, we discuss the
      functions of class I, II and III PI3Ks in autophagy and describe the protein
      effectors of PtdIns3P and PtdIns(3,4,5)P3 that promote or inhibit autophagy,
      respectively. We also provide examples of how PI3K-mediated control of autophagy
      is relevant to an understanding of tumour suppression and progression. 

PMID- 23953236
TI  - Acute-severe fatigue after anti-TNFalpha treatment: an early insidious side
      effect.

PMID- 23953237
TI  - Does the association with NOD2, autophagy and some pathogens really mean Crohn's
      disease is caused by uncontrolled infection?

PMID- 23953238
TI  - Faecal calprotectin but not C-reactive protein (CRP) or Crohn's Disease Activity
      Index (CDAI) may predict post-operative endoscopic recurrence of Crohn's disease.

PMID- 23953240
TI  - Unraveling galectin-1 as a novel therapeutic target for cancer.
AB  - Galectins belong to a family of carbohydrate-binding proteins with an affinity
      for beta-galactosides. Galectin-1 is differentially expressed by various normal
      and pathologic tissues and displays a wide range of biological activities. In
      oncology, galectin-1 plays a pivotal role in tumor growth and in the multistep
      process of invasion, angiogenesis, and metastasis. Evidence indicates that
      galectin-1 exerts a variety of functions at different steps of tumor progression.
      Moreover, it has been demonstrated that galectin-1 cellular localization and
      galectin-1 binding partners depend on tumor localization and stage. Recently,
      galectin-1 overexpression has been extensively documented in several tumor types
      and/or in the stroma of cancer cells. Its expression is thought to reflect tumor
      aggressiveness in several tumor types. Galectin-1 has been identified as a
      promising drug target using synthetic and natural inhibitors. Preclinical data
      suggest that galectin-1 inhibition may lead to direct antiproliferative effects
      in cancer cells as well as antiangiogenic effects in tumors. We provide an up-to
      date overview of available data on the role of galectin-1 in different molecular
      and biochemical pathways involved in human malignancies. One of the major
      challenges faced in targeting galectin-1 is the translation of current knowledge
      into the design and development of effective galectin-1 inhibitors in cancer
      therapy.

PMID- 23953239
TI  - High altitude journeys and flights are associated with an increased risk of
      flares in inflammatory bowel disease patients.
AB  - BACKGROUND AND AIMS: Hypoxia can induce inflammation in the gastrointestinal
      tract. However, the impact of hypoxia on the course of inflammatory bowel disease
      (IBD) is poorly understood. We aimed to evaluate whether flights and/or journeys
      to regions lying at an altitude of >2000 m above the sea level are associated
      with flare-ups within 4 weeks of the trip. METHODS: IBD patients with at least
      one flare-up during a 12-month observation period were compared to a group of
      patients in remission. Both groups completed a questionnaire. RESULTS: A total of
      103 IBD patients were included (43 with Crohn's disease (CD): mean age 39.3 +/-
      14.6 years; 60 with ulcerative colitis (UC): mean age 40.4 +/- 15.1 years). Fifty
      two patients with flare-ups were matched to 51 patients in remission. IBD
      patients experiencing flare-ups had more frequently undertaken flights and/or
      journeys to regions >2000 m above sea level within four weeks of the flare-up
      when compared to patients in remission (21/52 [40.4%] vs. 8/51 [15.7%], p=0.005).
      CONCLUSIONS: Journeys to high altitude regions and/or flights are a risk factor
      for IBD flare-ups occurring within 4 weeks of travel.

PMID- 23953241
TI  - Recurrent acute otitis media in infants: analysis of risk factors.
AB  - OBJECTIVE: Recurrence acute otitis media (RAOM) may cause a considerable
      morbidity and a great parental concern. The aim of this study was to analyze the
      risk factors that are likely to be responsible for RAOM in infants, and their
      impact on treatment failure. METHODS: A retrospective study on 340 infants with
      RAOM was conducted. Data were collected from hospital charts. A 10 days course of
      amoxicillin/clavulanate was used for treatment of recurrence, while surgical
      management in the form of adenoidectomy and/or myringotomy was reserved for
      patients with persistent disease. We analyzed various risk factors that may
      affect the prognosis of RAOM, including: age, prematurity, upper respiratory
      tract infections (URTI), duration of breastfeeding, use of pacifiers, parental
      smoking, seasonality, the presence of siblings (family size), gender, adenoid
      hypertrophy, allergy, and craniofacial abnormalities. RESULTS: Use of pacifiers,
      short duration of breastfeeding, older infantile age, winter season, URTI and
      presence of adenoid hypertrophy were identified as risk factors for RAOM.
      Treatment failure may be due to adenoid hypertrophy, short duration of
      breastfeeding and it is more common in older age infants. We did not find a
      significant association between RAOM and gender, prematurity, exposure to passive
      smoking, the presence of siblings, allergy, craniofacial abnormalities.
      CONCLUSIONS: Factors that may cause recurrence of the disease in infant
      population are use of pacifiers, short duration of breastfeeding, older infantile
      age, winter season, upper respiratory tract infections and adenoid hypertrophy.
      Also, treatment failure may be caused by adenoid hypertrophy and short duration
      of breastfeeding. Good understanding of these factors may help to decrease the
      recurrence rate and to improve the treatment of the disease.

PMID- 23953242
TI  - In-patient med-surg suicidality letter response.

PMID- 23953243
TI  - An association between kidney stone composition and urinary metabolic
      disturbances in children.
AB  - OBJECTIVE: To determine kidney stone composition in children and to correlate
      stone fractions with urinary pH and metabolic urinary risk factors. PATIENTS AND
      METHODS: We studied 135 pediatric patients with upper urinary tract lithiasis in
      whom excreted or extracted stones were available for analyses. Composition of
      stones was analyzed. A 24-hour urine assessment included volume, pH and daily
      excretions of calcium, oxalate, uric acid, cystine, creatinine, phosphate,
      magnesium and citrate. RESULTS: Calcium oxalate was the major component of 73%
      stones, followed by struvite (13%) and calcium phosphate (9%). Uric acid was
      present in almost half of stones, but in rudimentary amounts. The calcium oxalate
      content in calculi showed a strong relationship with calciuria, and moderate
      association with oxaluria, magnesuria and acidification of urine. The percent
      content of struvite presented reverse and lower correlations with regard to the
      above parameters. Calcium phosphate stone proportion had low associations with
      urinary risk factors. CONCLUSIONS: Calciuria, oxaluria, magnesuria and low urine
      pH exerted the biggest influence on calcium oxalate content in pediatric renal
      stones. Relationships of urinary risk factors with calculi calcium phosphate
      content were of unclear significance. Urinary citrate excretion did not
      significantly correlate with kidney stone composition in children.

PMID- 23953244
TI  - Warming effects on greenhouse gas fluxes in peatlands are modulated by vegetation
      composition.
AB  - Understanding the effects of warming on greenhouse gas feedbacks to climate
      change represents a major global challenge. Most research has focused on direct
      effects of warming, without considering how concurrent changes in plant
      communities may alter such effects. Here, we combined vegetation manipulations
      with warming to investigate their interactive effects on greenhouse gas emissions
      from peatland. We found that although warming consistently increased respiration,
      the effect on net ecosystem CO2 exchange depended on vegetation composition. The
      greatest increase in CO2 sink strength after warming was when shrubs were
      present, and the greatest decrease when graminoids were present. CH4 was more
      strongly controlled by vegetation composition than by warming, with largest
      emissions from graminoid communities. Our results show that plant community
      composition is a significant modulator of greenhouse gas emissions and their
      response to warming, and suggest that vegetation change could alter peatland
      carbon sink strength under future climate change. 

PMID- 23953245
TI  - New developments in the medical management of overactive bladder.
AB  - Overactive bladder (OAB) is a clinical syndrome describing the symptom complex of
      urgency, with or without urgency incontinence and is usually associated with
      frequency and nocturia. Whilst the majority of women will benefit from initial
      management with conservative and behavioural intervention a significant number
      will require medical therapy. Antimuscarinics are currently the most widely
      prescribed drugs for OAB although very often persistence with medication is
      limited due to lack of efficacy or intolerable adverse effects. The review,
      whilst giving a brief overview of OAB syndrome, will focus on new developments in
      drug therapy for OAB. In addition to evaluating new drugs with different methods
      of action it will also specifically focus on alternative modalities of treatment
      and how they may benefit patients with this troublesome and distressing
      condition. 

PMID- 23953246
TI  - Midwifery in the U.K.: how do we move midwifery led care from fringe to
      mainstream?

PMID- 23953247
TI  - Multiple Step-section Frozen Section sentinel lymph node biopsy--a review of 717
      patients.
AB  - Sentinel Lymph Node Biopsy (SLNB) is the standard of care for axillary staging in
      breast cancer. Multiple Step-section Frozen Section (MSFS) analysis is used in
      our institution for SLNB. This is performed intra-operatively by freezing
      sentinel lymph nodes to obtain multiple step-sections which are examined
      histologically for evidence of metastases. Patients whose sentinel lymph nodes
      contained macrometastases proceeded to an axillary node clearance during the same
      operation. 717 patients over a two and a half year period had MSFS analysis. With
      regards to macrometastases, MSFS analysis had a sensitivity of 93.8%, a
      specificity of 99.3%, a positive-predictive value of 97.4% and a negative
      predictive value of 98.2%. MSFS analysis of sentinel lymph nodes is a safe and
      accurate procedure. It is a relatively cost-effective alternative to molecular
      technologies relying on DNA amplification and more accurate than standard frozen
      section or touch-prep cytology. 

PMID- 23953249
TI  - Reduced activity of alkaline phosphatase due to host-guest interactions with
      humic superstructures.
AB  - Nuclear Magnetic Resonance (NMR) spectroscopy was applied to directly study the
      interactions between the alkaline phosphatase enzyme (AP) and two different humic
      acids from a volcanic soil (HA-V) and a Lignite deposit (HA-L). Addition of humic
      matter to enzyme solutions caused signals broadening in (1)H-NMR spectra, and
      progressive decrease and increase of enzyme relaxation (T1 and T2) and
      correlation (tauC) times, respectively. Spectroscopic changes were explained with
      formation of ever larger weakly-bound humic-enzyme complexes, whose translational
      and rotational motion was increasingly restricted. NMR diffusion experiments also
      showed that the AP diffusive properties were progressively reduced with formation
      of large humic-enzyme complexes. The more hydrophobic HA-L affected spectral
      changes more than the more hydrophilic HA-V. (1)H-NMR spectra also showed the
      effect of progressively greater humic-enzyme complexes on the hydrolysis of an
      enzyme substrate, the 4-nitrophenyl phosphate disodium salt hexahydrate (p-NPP).
      While AP catalysis concomitantly decreased NMR signals of p-NPP and increased
      those of nitrophenol, addition of humic matter progressively and significantly
      slowed down the rate of change for these signals. In agreement with the observed
      spectral changes, the AP catalytic activity was more largely inhibited by HA-L
      than by HA-V. Contrary to previous studies, in which humic-enzyme interactions
      were only indirectly assumed from changes in spectrophotometric behavior of
      enzyme substrates, the direct measurements of AP behavior by NMR spectroscopy
      indicated that humic materials formed weakly-bound host-guest complexes with
      alkaline phosphatase, and the enzyme catalytic activity was thereby significantly
      inhibited. These results suggest that the role of extracellular enzymes in soils
      may be considerably reduced when they come in contact with organic matter
      dissolved in the soil solution. 

PMID- 23953248
TI  - Analysis of mutations in the E6 oncogene of human papillomavirus 16 in cervical
      cancer isolates from Moroccan women.
AB  - BACKGROUND: Worldwide, cervical cancer is the second most common cancer in women.
      High-risk human papillomavirus (HPV) play a crucial role in the etiology of
      cervical cancer and the most prevalent genotype is HPV16. HPV 16 intratypic
      variants have been reported to differ in their prevalence, biological and
      biochemical properties. The present study was designed to analyze and identify
      HPV type 16 E6 variants among patients with cervical cancer in Morocco. METHODS:
      A total of 103 HPV16 positive samples were isolated from 129 cervical cancer
      cases, and variant status was subsequently determined by DNA sequencing of the E6
      gene. RESULTS: Isolates from patients were grouped into the European (E), African
      (Af) and North-American (NA1) phylogenetic clusters with a high prevalence of E
      lineage (58.3%). The Af and NA1 variants were detected in 31.1% and 11.6% of the
      HPV16 positive specimens, respectively, whereas, only 3% of cases were prototype
      E350T. No European-Asian (EA), Asian (As) or Asian-American (AA) variants were
      observed in our HPV16-positive specimens. At the amino acid level, the most
      prevalent non-synonymous variants were L83V (T350G), H78Y (C335T), E113D (A442C),
      Q14D (C143G/G145T) and R10I (G132T), and were observed respectively in 65%,
      41.8%, 38.8%, 30.1% and 23.3% of total samples.Moreover, HPV16 European variants
      were mostly identified in younger women at early clinical diagnosis stages.
      Whereas, HPV16 Af variants were most likely associated with cervical cancer
      development in older women with pronounced aggressiveness. CONCLUSION: This study
      suggests a predominance of E lineage strains among Moroccan HPV 16 isolates and
      raises the possibility that HPV16 variants have a preferential role in
      progression to malignancy and could be associated with the more aggressive nature
      of cervical cancer.

PMID- 23953250
TI  - Facile detection of photogenerated reactive oxygen species in TiO2 nanoparticles
      suspension using colorimetric probe-assisted spectrometric method.
AB  - This present study reports that reactive oxygen species (ROS), which mainly
      consist of hydroxyl (OH) and superoxide (O2(-)) radicals generated by the
      photocatalysis of TiO2 nanoparticles (TiO2 NPs) in suspension, can be
      quantitatively measured by the colorimetric probe-assisted spectrometric method
      without any interference by the TiO2 NPs. The interference effect of the TiO2 NPs
      with UV-vis spectroscopy was excluded by the selective separation of p
      nitrosodimethylaniline (RNO) and tetrazolium salt (XTT) (probe compounds for OH
      and O2(-), respectively) from the TiO2 NPs in the suspension by centrifugation at
      a specified ionic strength adjusted with phosphate buffer (KH2PO4/NaOH, PB)
      solution. This colorimetric probe-assisted spectrometric method was also
      successfully applied to measure the steady-state production of photogenerated ROS
      in a TiO2 NPs suspension. 

PMID- 23953251
TI  - Precision and accuracy of ST-EDXRF performance for As determination comparing
      with ICP-MS and evaluation of As deviation in the soil media.
AB  - The present study was conducted to (i) determine the precision and accuracy of
      arsenic measurement in soil samples using ST-EDXRF by comparison with the results
      of ICP-MS analyses and (ii) identify the relationship of As concentration with
      soil characteristics. For the analysis of samples, inductively coupled plasma
      mass spectrometry (ICP-MS) and energy dispersive X-ray fluorescence spectrometry
      (EDXRF) were performed. According to the results found in the soil samples, the
      addition of HCl to HNO3, used for the digestion gave significant variations in
      the recovery of As. However, spectral interferences between peaks for As and Pb
      can affect detection limits and accuracy for XRF analysis. When comparing the XRF
      and ICP-MS results a correlation was observed with R(2)=0.8414. This means that
      using a ST-EDXRF spectrometer, it is possible to achieve accurate and precise
      analysis by the calibration of certified reference materials and choosing an
      appropriate secondary target. On the other hand, with regard to soil
      characteristics analyses, the study highlighted that As is mostly
      anthropogenically enriched in the studied area. 

PMID- 23953252
TI  - User charges for health care services: some further thoughts.

PMID- 23953254
TI  - Lung cancer and mesothelioma risk assessment for a population environmentally
      exposed to asbestos.
AB  - Asbestos-related cancer risk is usually a concern restricted to occupational
      settings. However, recent published data on asbestos environmental concentrations
      in Thetford Mines, a mining city in Quebec, Canada, provided an opportunity to
      undertake a prospective cancer risk assessment in the general population exposed
      to these concentrations. Using an updated Berman and Crump dose-response model
      for asbestos exposure, we selected population-specific potency factors for lung
      cancer and mesothelioma. These factors were evaluated on the basis of population
      specific cancer data attributed to the studied area's past environmental levels
      of asbestos. We also used more recent population-specific mortality data along
      with the validated potency factors to generate corresponding inhalation unit
      risks. These unit risks were then combined with recent environmental measurements
      made in the mining town to calculate estimated lifetime risk of asbestos-induced
      lung cancer and mesothelioma. Depending on the chosen potency factors, the
      lifetime mortality risks varied between 0.7 and 2.6 per 100,000 for lung cancer
      and between 0.7 and 2.3 per 100,000 for mesothelioma. In conclusion, the
      estimated lifetime cancer risk for both cancers combined is close to Health
      Canada's threshold for "negligible" lifetime cancer risks. However, the risks
      estimated are subject to several uncertainties and should be confirmed by future
      mortality rates attributed to present day asbestos exposure. 

PMID- 23953255
TI  - Healthcare worker-related MRSA cluster in a German neonatology level III ICU: a
      true European story.
AB  - Here we investigated a cluster of eight newly Methicillin-resistant
      Staphylococcus aureus (MRSA)-colonized neonates at an ICU, and present data on
      molecular strain characterization as well as the source identification process in
      which we analyze the impact of MRSA-colonized HCWs. Molecular strain
      characterization revealed a unique pattern which was identified as spa-type t 127
      -an extremely rare strain type in Germany. Environmental sampling and screening
      of parents of colonized neonates proved negative. However, staff screening
      identified one healthcare worker (HCW; 1/134) belonging to a group of recently
      employed Romanian HCWs who was colonized with the spa 127 strain. Subsequent
      screening also detected MRSA in 9/51 Romanian HCWs (18%) and 7/9 (14% of all)
      isolates showed the same molecular pattern as the index case (spa/PFGE type). All
      carriers were successfully decolonized, after which no new patient cases
      occurred. As a result, we have now implemented a universal screening programme of
      all new employees as part of our infection control management strategy. MRSA
      colonized HCWs can act as a source for in hospital transmission. Since HCWs from
      high endemic countries are particular prone to being colonized, they may pose a
      risk to patients.

PMID- 23953256
TI  - Diagnostic accuracy of noninvasive coronary angiography with 320-slice computed
      tomography in the clinical routine: results from four-year clinical registry at a
      single center.

PMID- 23953257
TI  - Distinctive sodium and calcium regulation associated with sex differences in
      atrial electrophysiology of rabbits.
AB  - BACKGROUND: Sex and sodium/calcium regulation play critical roles in cardiac
      electrophysiology and atrial arrhythmogenesis. We investigated whether sodium and
      calcium contributed to sex differences in atrial electrophysiology. METHODS:
      Whole-cell patch clamp techniques and the indo-1 fluorometric ratio technique
      were used to investigate the ionic current and intracellular calcium in single
      isolated male and female rabbit myocytes from the left atrium posterior wall
      (LAPW) and right atrium (RA). RESULTS: Female LAPW (n=95) and RA (n=49) myocytes
      had larger cell widths (15.1+/-0.4 vs. 13.8+/-0.4 MUm, p<0.05; 14.9+/-0.6 vs.
      13.5+/-0.4 MUm, p<0.05) than male LAPW (n=142) and RA (n=57) myocytes. Male LAPW
      myocytes (n=26) had a higher incidence (57 vs. 16%, p<0.05) of delayed
      afterdepolarizations (DADs) than female LAPW myocytes (n=24) but there were
      similar incidences (20 vs. 20%, p>0.05) of DADs in male and female RA myocytes.
      The late sodium current, calcium transients, and sarcoplasmic reticulum calcium
      contents were larger in male than female LAPW myocytes but were similar in male
      and female RA myocytes. However, the ICa-L and nickel-sensitive sodium/calcium
      exchanger currents were similar between two groups. Different from those in
      female myocytes, ouabain (10 MUM) only induced repeated atrial beats (0 to 45%,
      p<0.05) in male myocytes (n=11). Moreover, ranolazine (3 MUM) perfusion (4.5+/
      0.6 vs. 1 min, p<0.05) was required to decrease the amplitude of DADs in male but
      not female LAPW myocytes. CONCLUSIONS: Increased late sodium currents and calcium
      contents may contribute to higher arrhythmogenesis in male LAPW myocytes.

PMID- 23953258
TI  - Prevention of acute myocardial infarction following blunt chest trauma.

PMID- 23953259
TI  - The interventricular conduction time is associated with response to cardiac
      resynchronization therapy: interventricular electrical delay.

PMID- 23953260
TI  - Challenge of coronary artery calcium by 64-multidetector computed tomography.

PMID- 23953261
TI  - Non-influence of lipid lowering therapy in atrial fibrillation recurrence.

PMID- 23953262
TI  - Left ventricular torsion abnormalities in patients after the arterial switch
      operation for transposition of the great arteries with intact ventricular septum.
AB  - BACKGROUND: The arterial switch operation (ASO) is currently the treatment of
      choice for infants with transposition of the great arteries (TGA). Little is
      known, however, about the alteration of anatomic left ventricular (LV) torsional
      mechanics after the operation. This study sought to evaluate LV torsion in
      patients of transposition of the great arteries with intact ventricular septum
      (TGA/IVS) using speckle tracking echocardiography. METHODS: Echocardiographic
      images were prospectively acquired in 32 infants (age range, 0.5-60 months) who
      successfully underwent ASO repair at about 1 month of age and in 48 normal
      controls. They were divided into early and late categories according to the age
      at the time of the study. The LV peak systolic torsion and systolic twisting and
      diastolic untwisting velocities were determined by speckle tracking. Mitral
      inflow velocity obtained by Pulsed-wave Doppler and mitral annular velocities
      drawn by septal tissue Doppler were also analyzed. RESULTS: Compared with
      controls, the early postoperative group (TGA1) had significantly higher septal
      E/e' (P=0.000). In contrast, septal e' velocity (P=0.000), LV peak apical
      rotation (P=0.01), twist (P=0.02) and peak untwisting velocity (PUV) (P=0.001)
      were lower in patients than in controls. For the normal younger group (Control1),
      PUV correlated positively with e' (r=0.68, P<0.001). No significant difference in
      LV twisting and untwisting was noted between the TGA2 and Control2. CONCLUSIONS:
      Two dimensional speckle tracking echocardiography may sensitively detect impaired
      LV torsional mechanics in patients with TGA/IVS early after ASO, and the
      impairment of LV relaxation leads to increased LV filling pressure which is
      consistent with higher E/e'. However, all patients recovered well thereafter and
      the overall midterm outcome of ASO is satisfactory.

PMID- 23953263
TI  - Mapping and ablation of focal arrhythmia: should we use three-dimensional mapping
      systems?

PMID- 23953264
TI  - Receptor for advanced glycation end products (RAGE) in atrial fibrillation.

PMID- 23953265
TI  - Diagnostic performance of noninvasive cardiac imaging modalities to detect
      obstructive coronary artery disease.

PMID- 23953266
TI  - Autologous transplantation of bone marrow stem cells prepared by the point-of
      care system in a patient with myocardial ischemia due to coronary artery chronic
      total occlusion.

PMID- 23953267
TI  - Diagnostic accuracy of optical coherence tomography parameters in predicting in
      stent hemodynamic severe coronary lesions: validation against fractional flow
      reserve.
AB  - BACKGROUND: By means of optical coherence tomography (OCT), coronary dimensions
      can be assessed accurately. However, whether OCT can identify hemodynamic
      significant coronary lesions as determined by fractional flow reserve (FFR) in
      patients with an in-stent lesion is not known. Therefore, we tried to assess the
      predictive value of OCT parameters in this setting as compared to FFR. METHODS
      AND RESULTS: In patients who underwent a percutaneous coronary intervention for
      an in-stent restenotic lesion, pre-, post-procedural and 6-month follow-up OCT
      and FFR acquisitions were performed. In case of an FFR <= 0.80, a lesion was
      classified as hemodynamically severe. Diagnostic efficiency of several OCT
      parameters were assessed with receiver operating characteristic curves. In 27
      patients, 66 coupled OCT and FFR segments were analyzed and compared. The
      diagnostic efficiencies of OCT-based minimal luminal diameter (MLD) and minimal
      luminal area (MLA) are good, with an area under the curve (AUC) of 0.83 (95%
      confidence interval: 0.74-0.93) and 0.83 (0.73-0.93), and a best cutoff value of
      1.77 mm (sensitivity 74% and specificity 78%) and 2.54 mm(2) (sensitivity 71% and
      specificity 84%), respectively. The diagnostic efficiency of OCT-based maximum
      neointimal area is moderate [AUC 0.73 (0.61-0.85)], and regarding maximum
      neointimal area stenosis, it is poor [0.39 (0.25-0.53)]. The corresponding best
      cutoff values are 5.01 mm(2) (sensitivity 66% and specificity 72%) and 49%
      (sensitivity 40% and specificity 66%), respectively. CONCLUSIONS: With OCT, a
      good diagnostic efficiency can be achieved in identifying coronary severity in in
      stent lesions in a per-group analysis. This hallmark provides an extra dimension,
      next to morphological information, when acquiring OCT images in scientific
      studies. However, OCT seems limited in a per-patient clinical decision making
      process due to reasonable but limited sensitivity and specificity in predicting
      coronary severity.

PMID- 23953268
TI  - Effect of educational attainment on incidence and mortality for ischemic heart
      and cerebrovascular diseases: a systematic review and trend estimation.

PMID- 23953269
TI  - A proof of concept study of tolcapone for pathological gambling: relationships
      with COMT genotype and brain activation.
AB  - Pathological gambling (PG) is a disabling disorder experienced by 1-3% of adults,
      and empirically validated treatments are lacking. Perturbations of prefrontal
      dependent cognitive functions are implicated in the pathophysiology of PG. The
      enzyme catechol-O-methyl-transferase (COMT) is responsible for degradation of
      dopamine in the cortices and thereby is known to regulate such cognitive
      functions and their neural substrates. The objective of this study was to
      determine whether tolcapone, a COMT inhibitor, improves symptoms of PG and to
      explore whether such effects are dependent on COMT val-158-met polymorphism
      status and relate to concomitant changes in fronto-parietal activation. Twenty
      four individuals with PG were enrolled in an 8-week trial of oral tolcapone
      (100mg/day titrated to 100mg thrice/day) and 12 undertook pre- and post-treatment
      fMRI to examine brain activation during an executive planning task in a pre
      defined fronto-parietal network. At baseline, patients with PG showed fronto
      parietal under-activation versus controls during executive planning. Treatment
      was associated with statistically significant reductions on PG-Yale Brown
      Obsessive Compulsive Scale (PG-YBOCS), the extent of which correlated
      significantly with augmentation of planning-related fronto-parietal activation.
      Symptom improvement was also significantly more pronounced in subjects with the
      val/val COMT polymorphism. Tolcapone improved PG symptoms, and the extent of
      symptomatic improvement was significantly related to augmentation of fronto
      parietal activation (fMRI probe) and COMT status. Objective genetic and fMRI
      markers hold promise in the search for targeting treatment and elucidating brain
      mechanisms associated with optimal clinical outcomes.

PMID- 23953270
TI  - Subjective well-being in schizophrenia: a randomised controlled open-label 12
      month non-inferiority study comparing quetiapine XR with risperidone (RECOVER).
AB  - This randomised 12-month open study analysed the effectiveness of quetiapine XR
      (400-800 mg) versus risperidone (2-6 mg) on subjective well-being in
      schizophrenia (NCT00600756). Primary objective was to demonstrate non-inferiority
      of quetiapine XR to risperidone in 6-month responder rate using the Subjective
      Well-Being under Neuroleptics scale (SWN-K) (per-protocol at Month 6 [PP 6]
      population). Non-inferiority was defined as the lower limit of the 95% confidence
      interval (CI) greater than -9.7% for the adjusted difference between quetiapine
      XR and risperidone. Secondary objectives included non-inferiority of quetiapine
      XR versus risperidone (lower limit of 95% CI greater than -7.5 points) for SWN-K
      change from baseline to Month 12 (PP 12). 798 patients were randomised
      (quetiapine XR, n=395; risperidone, n=403); at Month 12, 212 (54%) and 227 (56%)
      patients, respectively, completed the study. At Month 6, SWN-K responder rate in
      the PP 6 population was 65% (136/210) with quetiapine XR and 68% (158/232) with
      risperidone (adjusted treatment difference: -5.7%; 95% CI: -15.1, 3.7); thus, non
      inferiority could not be established. SWN-K change from baseline to Month 12 was
      23.2 points for quetiapine XR and 21.1 points for the risperidone group;
      treatment difference was 2.1 (95% CI: -0.8; 5.0); non-inferiority was established
      (PP 12). CONCLUSION: SWN-K response at 6 months was comparable between the two
      antipsychotics. However, with a lower than expected responder rate and a lower
      than expected number of evaluable patients in the PP 6 population, non
      inferiority was not demonstrated. A secondary objective (SWN-K total score)
      established non-inferiority of quetiapine XR to risperidone at Month 12.

PMID- 23953271
TI  - Pharmacological treatment and demographic characteristics of pediatric patients
      with Attention Deficit Hyperactivity Disorder, Sweden.
AB  - The aim of this study was to describe the pediatric population with ADHD and
      their pharmacological treatment. Using the Swedish National Patient Register and
      the Prescribed Drug Register we identified individuals below 19 years of age who
      were diagnosed or medically treated for ADHD for the first time 2006-2007. The
      unique patient identifiers were used to link information from the two registers
      to describe demographic characteristics, hospital care and drug treatments.
      Logistic regression model estimated the association between age, sex, frequency
      of hospitalization, diagnosis or treatment for other mental disorders and risk of
      gap in the treatment. Totally the study included 7931 patients of whom 74% were
      males. The mean age at first diagnosis was 12 years. Some 84% were medically
      treated for ADHD and approximately 90% received methylphenidate as the first
      substance. Combination therapy was rare and the most common combination was
      methylphenidate and atomoxetine. More than 55% of the patients, which could be
      followed up for two years after start of treatment, had at least one treatment
      gap of six months. Older age at diagnosis, lower number of hospitalizations and
      comorbidity with other mental disorders increased risks of gaps in medication.
      Approximately one fifth of the patients recorded in the National Patient Register
      as diagnosed with ADHD did not receive pharmacological treatment. Medication
      adherence seems to be low, when measured as gaps in treatment. 

PMID- 23953272
TI  - Early origin of viviparity and multiple reversions to oviparity in squamate
      reptiles.
AB  - Viviparity has putatively evolved 115 times in squamates (lizards and snakes),
      out of only ~ 140 origins in vertebrates, and is apparently related to colder
      climates and other factors such as body size. Viviparity apparently evolves from
      oviparity via egg-retention, and such taxa may thus still have the machinery to
      produce thick-shelled eggs. Parity mode is also associated with variable
      diversification rates in some groups. We reconstruct ancestral parity modes
      accounting for state-dependent diversification in a large-scale phylogenetic
      analysis, and find strong support for an early origin of viviparity at the base
      of Squamata, and a complex pattern of subsequent transitions. Viviparous lineages
      have higher rates of speciation and extinction, and greater species turnover
      through time. Viviparity is associated with lower environmental and body
      temperatures in lizards and amphisbaenians, but not female mass. These results
      suggest that parity mode is a labile trait that shifts frequently in response to
      ecological conditions. 

PMID- 23953273
TI  - Theoretical and experimental indicators of falls during pregnancy as assessed by
      postural perturbations.
AB  - Throughout pregnancy, women experience physical, physiological, and hormonal
      alterations that are often accompanied by decreased postural control. According
      to one study, nearly 27% of pregnant women fell while pregnant. This study had
      two objectives: (1) to characterize the postural responses of pregnant fallers,
      nonfallers, and controls to surface perturbations, and (2) to develop a
      mathematical model to gain insights into the postural control strategies of each
      group. This retrospective analysis used experimental data obtained from 15 women
      with a fall history during pregnancy, 14 women without a fall history during
      pregnancy, and 40 nonpregnant controls. Small, medium, and large translational
      support surface perturbations in the anterior and posterior directions were
      performed during the pregnant participants' second and third trimesters. A two
      segmented mathematical model of bipedal stance was developed and parameterized,
      and optimization tools were used to identify ankle and hip stiffness, viscosity,
      and the feedback time delay by searching for the best fits to experimental COP
      data. The peak differences between the center of pressure and center of gravity
      (COP-COG) values were significantly smaller for the pregnant fallers compared
      with the pregnant nonfallers and controls (p<0.01). Perturbation magnitude was a
      significant factor (p<0.01), but perturbation direction was not (p=0.24). Model
      fits were obtained with a mean goodness of fit value of R(2)=0.92. Theoretical
      results indicated that pregnant nonfallers had higher ankle stiffness compared
      with the pregnant fallers and the controls, which suggests that ankle stiffness
      itself may be the dominant reason for the different dynamic response
      characteristics (e.g., peak COP-COG) observed. We conclude that increasing ankle
      stiffness could be an important strategy to prevent falling by pregnant women.

PMID- 23953274
TI  - Kinetic patterns of treadmill walking in preadolescents with and without Down
      syndrome.
AB  - This study investigated the effect of both walking speed and external ankle load
      on the kinetic patterns of treadmill walking in preadolescents with and without
      Down syndrome (DS). Ten preadolescents with DS and ten age- and gender-matched
      children with typical development (TD) participated in this study. We manipulated
      two treadmill speeds and two external ankle loads. Treadmill speeds were equal to
      75% and 100% of the preferred overground walking speed. Two load conditions were
      with and without external ankle load which was equal to 2% of body weight on each
      side. We used an instrumented treadmill to collect vertical ground reaction force
      (GRF). Both timing and magnitude of peak GRFs, the loading and unloading rates,
      and various impulses were calculated from the GRF data. The results show that the
      DS group produced a shorter duration of propulsion, a lower FZ2 (second peak GRF)
      and vertical propulsive impulse, a higher loading rate and a lower unloading rate
      than the TD group. At a faster treadmill speed the DS group increased the
      duration of propulsion, the unloading rate and the vertical propulsive impulse,
      but reduced the magnitude of FZ2. External ankle load helped the DS group
      increase FZ2 and vertical propulsive impulse and might facilitate the push off
      and the initiation of leg swing during treadmill walking. External ankle load may
      therefore be included in the future physical intervention and exercise programs
      for the DS group to strengthen leg muscles and develop more efficient push off
      during locomotion. 

PMID- 23953275
TI  - Regulation of distinct pools of amyloid beta-protein by multiple cellular
      proteases.
AB  - Alzheimer's disease (AD) is a progressive, age-related neurodegenerative disorder
      characterized by extracellular and intracellular deposition of the amyloid beta
      protein (Abeta). The study of rare, familial forms of AD has shown that sustained
      elevations in the production of Abeta (either all forms or specific pathogenic
      variants thereof) are sufficient to trigger the full spectrum of cognitive and
      histopathological features of the disease. Although the exact cause or causes
      remain unknown, emerging evidence suggests that impairments in the clearance of
      Abeta, after it is produced, may underlie the vast majority of sporadic AD cases.
      This review focuses on Abeta-degrading proteases (AbetaDPs), which have emerged
      as particularly important mediators of Abeta clearance. A wide variety of
      proteases that - by virtue of their particular regional and subcellular
      localization profiles - define distinct pools of Abeta have been identified.
      Different pools of Abeta, in turn, may contribute differentially to the
      pathogenesis of the disease. The study of individual AbetaDPs, therefore,
      promises to offer new insights into the mechanistic basis of AD pathogenesis and,
      ultimately, may facilitate the development of effective methods for its
      prevention or treatment or both. 

PMID- 23953276
TI  - [Capitolunate arthrodesis: 12 patients followed-up an average of 10 years].
AB  - The aim of the study was to evaluate long-term results of capitolunate
      arthrodesis for the treatment of posttraumatic degenerative wrist disorders. A
      capitolunate arthrodesis was performed on 12 patients, three women and nine men,
      of 45 years on average (28-66). Ten patients were manual workers. Dominant side
      was involved in seven cases. Indications were nine scapholunate dissociations
      (SLAC) and three scaphoid non-unions (SNAC) with degenerative lesions. Fixation
      of the arthrodesis was performed with K-wires in seven, K-wires and staples in
      two, and only staples in three. Patients were reviewed at 118 months of average
      follow-up (72-168). One complete wrist arthrodesis was necessary one year after
      the capitolunate arthrodesis for an evolutive painful osteoarthritis. For the 11
      remaining patients, pain on visual analogic scale (VAS) was 0.5. The
      flexion/extension arc was decreased of 25 degrees  and strength of 6kg compared
      to preoperative values. DASH score was equal to 33.7 points, Cooney score to 77.2
      points and Mayo score to 82.8 points. Radiolunate and capitolunate angles were
      decreased of 4.9 degrees  and 6.2 degrees  respectively compared to preoperative
      values. Some complications occurred: evolutive osteoarthritis between triquetrum
      and lunate in two, non-union of the arthrodesis in one, and reflex sympathetic
      dystrophy in two. Nine patients were able to return to their previous
      professional activities. Capitolunate arthrodesis allowed restoring a pain free
      and functional wrist in eight out of the 11 patients reviewed. Results were
      maintained with follow-up. It is a satisfactory therapeutic alternative to four
      corners fusion for chronic instability of the wrist with osteoarthritis. LEVEL OF
      EVIDENCE: IV.

PMID- 23953277
TI  - Continuous in situ diffusion of ropivacaine for ambulatory congenital hand
      disorders surgery in young children.
AB  - Pediatric ambulatory surgery presents a specific set of challenges to the
      anesthesiologist. Similarly to adult ambulatory surgery, we report four
      ambulatory surgical procedures in two young children with congenital hand
      disorders. For each surgical procedure pain was controlled with continuous in
      situ infusion of ropivacaine. 

PMID- 23953278
TI  - Chronic leg ulceration associated with polycythemia vera responding to
      ruxolitinib (Jakafi((r))).
AB  - We present the case of a 63-year-old white male with bilateral chronic leg ulcers
      due to polycythemia vera and hydroxyurea therapy who demonstrated dramatic
      healing of his wounds in response to ruxolitinib (Jakafi((r)), Novartis), a novel
      Janus kinase-1 and -2 inhibitor. This patient's wound had previously been
      refractory to multiple surgical interventions and immunosuppression. After the
      initiation of ruxolitinib, the patient underwent successful split-thickness skin
      grafting, with resultant healing of his wounds. He was stable without prednisone
      and other immunosuppressant therapy and had healed at 6 months. Ruxolitinib
      therapy could represent a novel option for patients who develop persistent
      inflammatory wounds in the setting of polycythemia vera and hydroxyurea therapy. 

PMID- 23953279
TI  - Impact of three radiographic methods in the outcome of nonsurgical endodontic
      treatment: a five-year follow-up.
AB  - INTRODUCTION: The periapical film radiograph (PFR) and digital periapical
      radiograph (DPR) techniques have some limitations in the visualization of small
      periapical lesions (PLs) when compared with cone-beam computed tomography (CBCT).
      However, the evidence supporting their effectiveness is very limited. This
      retrospective longitudinal cohort study evaluated the outcome of endodontic
      treatments measured/monitored by PFR, DPR, and CBCT during a 5-year follow-up and
      also determined the prognostic factors that influenced treatment success.
      METHODS: A total of 132 teeth (208 roots) with vital pulps received endodontic
      treatment. The periapical indexes with scores >=2 for PFR and DPR and >=1 for
      CBCT indicated the presence of PLs. Prognostic factors were determined by
      bivariate and multivariate analyses. Statistical significance was defined at a P
      level <.05. RESULTS: CBCT detected a higher number of PLs (18.7%, n = 39 roots),
      followed by DPR (7.7%, n = 16 roots) and PFR (5.7%, n = 12 roots). Likewise, CBCT
      was more sensitive than PFR and DPR in detecting deficiencies in extension and
      density of the root canal filling (P <= .001). Of the 17 prognostic factors
      evaluated, 4 were significantly associated with poor outcome to the treatment (P
      < .05): root canal curvature, disinfection of gutta-percha, presence of missed
      canals, and the quality of definitive coronal restoration. CONCLUSIONS: The
      success outcome of endodontic treatment after 5 years in teeth with vital pulps
      varied with each radiographic method: 94.3%/PFR, 92.3%/DPR, and 81.3%/CBCT.

PMID- 23953280
TI  - Outcomes of hospitalizations attributed to periapical abscess from 2000 to 2008:
      a longitudinal trend analysis.
AB  - INTRODUCTION: Root canal therapy is a highly successful in-office treatment and
      preventive measure against periapical abscesses. Left untreated, periapical
      abscesses can have serious consequences that can lead to hospitalization. This
      study observes the trends of hospitalizations attributed to periapical abscesses.
      METHODS: A retrospective analysis of the Nationwide Inpatient Sample (years 2000
      2008) was used; we selected cases with a primary diagnosis of a periapical
      abscess with/without sinus involvement. The demographic characteristics and
      outcomes were examined. Each individual hospitalization was the unit of analysis.
      RESULTS: During the 9-year study period, a total of 61,439 hospitalizations were
      primarily attributed to periapical abscesses in the United States. The average
      age was 37 years, and 89% of all hospitalizations occurred on an emergency/urgent
      basis. The mean length of stay was 2.96 days, and a total of 66 patients died in
      hospitals. Medicare, Medicaid, and private insurance plans paid for 18.7%, 25.2%,
      and 33.4% of hospitalizations, respectively. Uninsured patients accounted for
      18.5% of hospitalizations. Significant predictors that influenced both hospital
      charges and length of stay included age, race, insurance status, a periapical
      abscess with sinus involvement, geographic region of country, the Charlson
      comorbidity index, and the year of study (P < .05). CONCLUSIONS: The current
      study highlights the increasing burden of hospitalization of patients with
      periapical abscesses over a 9-year study period from 2000 to 2008. The high-risk
      groups likely to seek a hospital setting for the treatment of periapical
      abscesses were identified as were groups associated with higher hospital charges
      and a longer length of stay.

PMID- 23953281
TI  - A novel method to estimate the volume of bone defects using cone-beam computed
      tomography: an in vitro study.
AB  - INTRODUCTION: The routine use of high-resolution images derived from 3
      dimensional cone-beam computed tomography (CBCT) datasets enables the linear
      measurement of lesions in the maxillary and mandibular bones on 3 planes of
      space. Measurements on different planes would make it possible to obtain real
      volumetric assessments. In this study, we tested, in vitro, the accuracy and
      reliability of new dedicated software developed for volumetric lesion assessment
      in clinical endodontics. METHODS: Twenty-seven bone defects were created around
      the apices of 8 teeth in 1 young bovine mandible to simulate periapical lesions
      of different sizes and shapes. The volume of each defect was determined by taking
      an impression of the defect using a silicone material. The samples were scanned
      using an Accuitomo 170 CBCT (J. Morita Mfg Co, Kyoto, Japan), and the data were
      uploaded into a newly developed dedicated software tool. Two endodontists acted
      as independent and calibrated observers. They analyzed each bone defect for
      volume. The difference between the direct volumetric measurements and the
      measurements obtained with the CBCT images was statistically assessed using a
      lack-of-fit test. A correlation study was undertaken using the Pearson product
      moment correlation coefficient. Intra- and interobserver agreement was also
      evaluated. RESULTS: The results showed a good fit and strong correlation between
      both volume measurements (rho > 0.9) with excellent inter- and intraobserver
      agreement. CONCLUSIONS: Using this software, CBCT proved to be a reliable method
      in vitro for the estimation of endodontic lesion volumes in bovine jaws.
      Therefore, it may constitute a new, validated technique for the accurate
      evaluation and follow-up of apical periodontitis.

PMID- 23953282
TI  - Comparative evaluation of the efficacy of 2% lidocaine containing 1:200,000
      epinephrine with and without hyaluronidase (75 IU) in patients with irreversible
      pulpitis.
AB  - INTRODUCTIONS: The purpose of this study was to determine the anesthetic efficacy
      of lidocaine containing epinephrine compared with lidocaine containing
      epinephrine plus hyaluronidase (75 IU) when performing an inferior alveolar nerve
      block. METHODS: Patients complaining of pain in the mandibular posterior teeth
      were selected. Based on their chief complaint, proper clinical and radiographic
      examinations were performed. Among them, 40 subjects diagnosed with irreversible
      pulpitis were selected. The inferior alveolar nerve block was induced using 3 mL
      2% lidocaine with epinephrine. Hyaluronidase (75 IU) or a placebo was injected 30
      minutes after the beginning of pulpal anesthesia (randomized and double-blind
      trial). The duration of the effect in the pulpal and gingival tissues was
      evaluated by the response to painful electrical stimuli applied to the adjacent
      premolar and by mechanical stimuli (pinprick) to the buccal gingiva,
      respectively. RESULTS: In both pulpal and gingival tissues, the duration of the
      anesthetic effects with hyaluronidase was longer than with placebo. CONCLUSIONS:
      Hyaluronidase increased the duration of the effects of lidocaine in inferior
      alveolar nerve blocks.

PMID- 23953283
TI  - Potential correlation between statins and pulp chamber calcification.
AB  - INTRODUCTION: 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors
      (statins) are the first-line pharmaceuticals for the prevention and treatment of
      dyslipidemia. A recent investigation has shown that statins induced odontoblastic
      differentiation of dental pulp stem cells. Statins enhance the differentiation of
      human dental pulp cells by up-regulating mineralization nodules and odontogenic
      markers. This study tested the hypothesis that the systemic administration of
      statins results in increased dental pulp calcification. METHODS: This
      retrospective case-control study used digital bitewing radiographs of mandibular
      molars. Subjects (N = 90) aged >=60 years were assigned to either test (n = 45)
      or control (n = 45) groups based on the systemic use of statins. The dimensions
      of the pulp chambers were measured using a standardized method for height and
      mesiodistal distances. The chi-square test was used to analyze the data. Multiple
      linear regression model analysis was performed to explore the association between
      statin intake and pulp calcification. RESULTS: Three of the 45 mandibular molars
      in the test group exhibited almost complete pulp chamber obliteration. There was
      a significant reduction in pulp chamber height ratio shown in the statin group
      compared with the control group (P < .0001). When the mesiodistal width was
      compared between the 2 groups, there was no significant difference (P = .3730).
      CONCLUSIONS: The significant increase of calcification and loss of vertical
      height of the pulp chamber observed in mandibular molars in patients on statin
      medication indicated a possible increased odontoblastic activity. Therefore,
      systemic statins could be a contributing factor for pulp chamber calcification.

PMID- 23953284
TI  - Three-dimensional analysis of root canal curvature and direction of maxillary
      lateral incisors by using cone-beam computed tomography.
AB  - INTRODUCTION: Root canal curvature can affect the technical quality of endodontic
      treatment. Prior studies measured canal curvature mainly by 2-dimensional
      radiography. The aim of this study was to measure the 3-dimensional (3D) root
      canal curvature and canal direction of maxillary lateral incisors by using cone
      beam computed tomography (CBCT) and mathematical modeling. METHODS: The CBCT
      images of 186 maxillary lateral incisors from 110 patients were used to measure
      3D root canal curvature by using V-works and kappa software. In addition, the
      direction of each root canal was determined by measuring the orientation of the
      apical one-third with respect to the coronal two-thirds. RESULTS: All 186
      maxillary lateral incisors were found to have canal curvature that was mainly
      oriented in the disto-palatal direction. The point of maximum curvature was
      located 0.5 mm from the root apex. CONCLUSIONS: Maxillary lateral incisors have
      3D canal curvature that is maximal near the root apex, oriented in the disto
      palatal direction. These CBCT analyses provide valuable information for root
      canal instrumentation of maxillary lateral incisors.

PMID- 23953285
TI  - Morphologic micro-computed tomography analysis of mandibular premolars with three
      root canals.
AB  - INTRODUCTION: This study aimed to describe the anatomy of mandibular premolars
      with type IX canal configuration by using micro-computed tomography. METHODS:
      Mandibular premolars with radicular grooves (n = 105) were scanned, and 16 teeth
      with type IX configuration were selected. Number and location of canals,
      distances between anatomic landmarks, occurrence of apical delta, root canal
      fusion, and furcation canals, as well as 2-dimensional (area, perimeter,
      roundness, major and minor diameters) and 3-dimensional (volume, surface area,
      and structure model index) analysis were performed. Data were statistically
      compared by using analysis of variance and Kruskal-Wallis tests (alpha = 0.05).
      RESULTS: Overall, specimens had 1 root with a main canal that divided into
      mesiobuccal, distobuccal, and lingual canals at the furcation level. Mean length
      of the teeth was 22.9 +/- 2.06 mm, and the configuration of the pulp chamber was
      mostly triangle-shaped. Mean distances from the furcation to the apex and
      cementoenamel junction were 9.14 +/- 2.07 and 5.59 +/- 2.19 mm, respectively.
      Apical delta, root canal fusion, and furcation canals were present in 4, 5, and
      10 specimens, respectively. No statistical differences were found in the 2
      dimensional and 3-dimensional analyses between root canals (P > .05).
      CONCLUSIONS: Type IX configuration of the root canal system was found in 16 of
      105 mandibular premolars with radicular grooves. Most of the specimens had a
      triangle-shaped pulp chamber. Within this anatomic configuration, complexities of
      the root canal systems such as the presence of furcation canals, fusion of
      canals, oval-shaped canals in the apical third, small orifices at the pulp
      chamber level, and apical delta were also observed.

PMID- 23953286
TI  - Microbial analysis in primary and persistent endodontic infections by using
      pyrosequencing.
AB  - INTRODUCTION: The aim of this study was to investigate the bacterial community
      profile of intracanal microbiota in primary and persistent endodontic infections
      associated with asymptomatic chronic apical periodontitis by using GS-FLX
      Titanium pyrosequencing. The null hypothesis was that there is no difference in
      diversity of overall bacterial community profiles between primary and persistent
      infections. METHODS: Pyrosequencing analysis from 10 untreated and 8 root-filled
      samples was conducted. RESULTS: Analysis from 18 samples yielded total of 124,767
      16S rRNA gene sequences (with a mean of 6932 reads per sample) that were
      taxonomically assigned into 803 operational taxonomic units (3% distinction), 148
      genera, and 10 phyla including unclassified. Bacteroidetes was the most abundant
      phylum in both primary and persistent infections. There were no significant
      differences in bacterial diversity between the 2 infection groups (P > .05). The
      bacterial community profile that was based on dendrogram showed that bacterial
      population in both infections was not significantly different in their structure
      and composition (P > .05). CONCLUSIONS: The present pyrosequencing study
      demonstrates that persistent infections have as diverse bacterial community as
      primary infections.

PMID- 23953287
TI  - MMP-7 and TIMP-1, new targets in predicting poor wound healing in apical
      periodontitis.
AB  - INTRODUCTION: Matrix metalloproteinases (MMPs) and the tissue inhibitors of
      metalloproteinases (TIMPs) are strongly associated with tissue destruction
      because of inflammation. In this study, we investigated the expression of MMPs
      and TIMPs messenger RNA and protein levels in apical periodontitis lesions.
      METHODS: Tissue samples from patients presenting clinical signs of chronic apical
      abscess (CAA) or asymptomatic apical periodontitis (AAP) were collected
      postoperatively and used for gene expression analysis of MMP-2, -3, -7, -9, -14, 
      16, and -25; TIMP-1; and TIMP-2 in real-time polymerase chain reaction.
      Immunohistochemistry was also performed to detect the expression of MMP-7 and
      TIMP-1 proteins. Lastly, U-937 cells were induced to terminal differentiation
      into macrophages, infected with purified Escherichia coli lipopolysaccharide, and
      assessed for the expression of MMP-7 and TIMP-1 using immunocytochemistry and
      confocal microscopy. RESULTS: Significantly higher messenger RNA levels were
      found for all genes in AAP and CAA samples when compared with healthy control
      samples (P < .001). AAP cases exhibited significantly higher TIMP-1 when compared
      with CAA cases, whereas CAA cases showed higher MMP-2, MMP-7, and MMP-9 messenger
      RNA levels (P < .05). We also detected positive the expression of MMP-7 and TIMP
      1 proteins in the tissue samples. The expression of both MMP-7 and TIMP-1 were
      increased in lipopolysaccharide-stimulated cells compared with nonstimulated
      cells and appear to colocalize in the Golgi apparatus. CONCLUSIONS: MMPs appear
      to have an influential role in CAA cases in which ongoing tissue destruction is
      observed. TIMPs are preferentially associated with AAP, perhaps as a subsequent
      defense mechanism against excessive destruction. Taken together, our findings
      implicate MMP and TIMP molecules in the dynamics of inflammatory periapical
      lesion development.

PMID- 23953288
TI  - Application of high-frequency radio waves to direct pulp capping.
AB  - INTRODUCTION: In vital pulp therapy such as direct pulp capping, clinical success
      rates depend on achieving hemostasis in exposed pulp tissue. For hemostasis of
      exposed pulp tissue, gentle pressure by cotton pellets moistened with sodium
      hypochlorite is most commonly used. However, more rapid and reliable methods are
      necessary. Therefore, we focused on high-frequency radio waves (HRW). METHODS: To
      evaluate reparative dentin induction by HRW, we used a rat direct pulp capping
      model and performed hemostasis by using HRW of several strengths, covering the
      pulp with calcium hydroxide as a direct capping agent. After 14 or 28 days, rats
      were killed, and reparative dentin and pulp inflammation were investigated
      histologically. RESULTS: Radio wave-induced hemostasis required less time when
      compared with the control group. Reparative dentin with regularly arranged
      dentinal tubules was observed in the HRW group. CONCLUSIONS: HRW induce
      hemostasis and produce high-quality reparative dentin and reduced pulpal
      inflammation.

PMID- 23953289
TI  - Hydrogen peroxide induces apoptosis in human dental pulp cells via caspase-9
      dependent pathway.
AB  - INTRODUCTION: Reactive oxygen species are a group of metabolic intermediates
      produced during oxidative metabolism in eukaryotic cells. They include superoxide
      anion (O2(-)), hydrogen peroxide (H2O2), hydroxyl radical (.OH), and (1)O2. Of
      these intermediates, H2O2 is the most stable. Dental pulp cells can be invaded by
      tooth bleaching, laser radiation, and dental materials. This can influence the
      intracellular level of reactive oxygen species. Apoptosis, which is the best
      known form of programmed cell death, is pivotal to tissue development and
      regeneration. Little information is available regarding the relationship between
      H2O2 and apoptosis of human dental pulp cells (hDPCs). The purpose of this study
      was to investigate whether H2O2 can induce apoptosis in hDPCs and its signaling
      way. METHODS: HDPCs were obtained by using a modified tissue explant technique in
      vitro and cultured at 37 degrees C, 20% O2 (5% CO2, 95% air) in Dulbecco modified
      Eagle medium. Cell viability was investigated by methyl-thiazol-tetrazolium
      assay. Cell apoptosis was detected by using the annexin V-fluorescein
      isothiocyanate/propidium iodide apoptosis assay and flow cytometry. Expression of
      activated caspase-3, cleaved caspase-9, and beta-actin was analyzed by using
      Western blot. RESULTS: Cell viability of hDPCs decreased more in treated groups
      than in the control group from days 1 to 7. The relative number of apoptotic
      cells and the expression of activated caspase-3 and cleaved caspase-9 were much
      higher in groups exposed to 20 and 50 MUmol/L H2O2. CONCLUSIONS: These results
      imply that low concentrations of H2O2 are cytotoxic to hDPCs and induce apoptosis
      in hDPCs in a caspase-9-dependent way.

PMID- 23953290
TI  - 2-Hydroxyethyl methacrylate inhibits migration of dental pulp stem cells.
AB  - INTRODUCTION: Cell migration is an important step in pulpal wound healing.
      Although components in the resin-based dental materials are known to have adverse
      effects on pulp wound healing including proliferation and mineralization, their
      effects on cell migration have been scarcely examined. Here, we investigated the
      effects of 2-hydroxyethyl methacrylate (HEMA) on the migration of dental pulp
      stem cells (DPSC) in vitro. METHODS: Cell viability was assessed using the MTT (3
      (4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay, and cell
      migration was evaluated using the wound scratch assay and transwell migration
      assay at noncytotoxic doses. The Western blot was used to examine pathways
      associated with migration such as focal adhesion kinase, mitogen-activated
      protein kinase, and glycogen synthase kinase 3. RESULTS: There were no drastic
      changes in the cell viability below 3 mmol/L HEMA. When DPSCs were treated with
      HEMA at 0.5, 1.0, and 2.5 mmol/L, cell migration was diminished. HEMA-treated
      DPSCs exhibited the loss of phosphorylated focal adhesion kinase in a dose
      dependent manner. The HEMA-mediated inhibition of cell migration was associated
      with phosphorylation of p38 but not glycogen synthase kinase 3, Extracellular
      signal-related kinase (ERK), or c-Jun N-terminal kinase (JNK) pathways. When we
      inhibited the p38 signaling pathway using a p38 inhibitor, the migration of DPSCs
      was suppressed. CONCLUSIONS: HEMA inhibits the migration of dental pulp cells in
      vitro, suggesting that poor pulpal wound healing under resin-based dental
      materials may be caused, in part, by the inhibition of cell migration by HEMA.

PMID- 23953292
TI  - Timing for composite resin placement on mineral trioxide aggregate.
AB  - INTRODUCTION: The aim of this study was to investigate the proper time to restore
      composite resin over mineral trioxide aggregate (MTA). METHODS: Thirty-five
      samples of MTA blocks were divided into 7 groups with 3 different times (10
      minutes, 1 day, and 7 days) selected for restoring the composite resin over MTA
      with and without bonding resin, and a control group was included for comparison.
      After 21 days, the distances between MTA and the composite resin or between MTA
      and the bonding agent on sectioned planes along the long axis were measured using
      a scanning electron microscope (*2,000 magnification). The hardness of the MTA
      near the composite resin was presented as the Vickers microhardness. RESULTS:
      There were no gaps at the interface in the 10-minute groups, the 1-day group with
      a bonding agent, and the 7-day group with a bonding agent. The groups without a
      bonding agent at 1 and 7 days presented a separation or gap at the interface. The
      value of the Vickers microhardness in the 1-day groups was significantly
      decreased compared with those of the other groups regardless of the presence or
      absence of a bonding agent. CONCLUSIONS: These findings suggest that composite
      resin with a bonding agent over MTA can be restored almost immediately after MTA
      mixing during a single visit.

PMID- 23953291
TI  - In vitro osteogenic/dentinogenic potential of an experimental calcium
      aluminosilicate cement.
AB  - INTRODUCTION: Calcium aluminosilicate cements are fast-setting, acid-resistant,
      bioactive cements that may be used as root-repair materials. This study examined
      the osteogenic/dentinogenic potential of an experimental calcium aluminosilicate
      cement (Quick-Set) by using a murine odontoblast-like cell model. METHODS: Quick
      Set and white ProRoot MTA (WMTA) were mixed with the proprietary gel or deionized
      water, allowed to set completely in 100% relative humidity, and aged in complete
      growth medium for 2 weeks until rendered non-cytotoxic. Similarly aged Teflon
      disks were used as negative control. The MDPC-23 cell line was used for
      evaluating changes in mRNA expressions of genes associated with
      osteogenic/dentinogenic differentiation and mineralization (quantitative reverse
      transcription polymerase chain reaction), alkaline phosphatase enzyme production,
      and extracellular matrix mineralization (alizarin red S staining). RESULTS: After
      MDPC-23 cells were incubated with the materials in osteogenic differentiation
      medium for 1 week, both cements showed up-regulation in ALP and DSPP expression.
      Fold increases in these 2 genes were not significantly different between Quick
      Set and WMTA. Both cements showed no statistically significant up-regulation/down
      regulation in RUNX2, OCN, BSP, and DMP1 gene expression compared with Teflon.
      Alkaline phosphatase activity of cells cultured on Quick-Set and WMTA were not
      significantly different at 1 week or 2 weeks but were significantly higher (P <
      .05) than Teflon in both weeks. Both cements showed significantly higher calcium
      deposition compared with Teflon after 3 weeks of incubation in mineralizing
      medium (P < .001). Differences between Quick-Set and WMTA were not statistically
      significant. CONCLUSIONS: The experimental calcium aluminosilicate cement
      exhibits similar osteogenic/dentinogenic properties to WMTA and may be a
      potential substitute for commercially available tricalcium silicate cements.

PMID- 23953293
TI  - Comparative antibacterial efficacies of hydrodynamic and ultrasonic irrigation
      systems in vitro.
AB  - INTRODUCTION: To ensure root canal treatment success, endodontic microbiota
      should be efficiently reduced. The in vitro bactericidal effects of a
      hydrodynamic system and a passive ultrasonic irrigation system were compared.
      METHODS: Single-rooted extracted teeth (n = 250) were contaminated with
      suspensions of Enterococcus faecalis ATCC 29212, mixed aerobic cultures, or mixed
      anaerobic cultures. First, the antibacterial effects of the hydrodynamic system
      (RinsEndo), a passive ultrasonic irrigation system (Piezo smart), and manual
      rinsing with 0.9% NaCl (the control) were compared. Colony-forming units were
      counted. Second, the 2 systems were used with 1.5% sodium hypochlorite (NaOCl)
      alone or NaOCl + 0.2% chlorhexidine (CHX). The colony-forming units in the
      treated and untreated roots were determined during a period of 5 days. RESULTS:
      Both irrigation systems reduced bacterial numbers more effectively than manual
      rinsing (P < .001). With NaCl, ultrasonic activated irrigation reduced bacterial
      counts significantly better than hydrodynamic irrigation (P = .042). The NaOCl +
      CHX combination was more effective than NaOCl alone for both systems (P < .001),
      but hydrodynamic irrigation was more effective with NaOCl + CHX than the passive
      ultrasonic irrigation system. CONCLUSIONS: Both irrigation systems, when combined
      with NaOCl + CHX, removed bacteria from root canals.

PMID- 23953294
TI  - Comparison of warm vertical compaction protocols to obturate artificially created
      defects in the apical one-third.
AB  - INTRODUCTION: The purpose of this study was to evaluate the ability of 4
      different warm vertical compaction protocols to obturate artificially created
      defects in the apical one-third of a root canal system by using a split-tooth
      model. METHODS: Four warm vertical protocols used (A) continuous down-pack and
      continuous backfill, (B) continuous down-pack and incremental backfill, (C)
      incremental down-pack and continuous backfill, and (D) incremental down-pack and
      incremental backfill. Three artificially created defects were placed 2, 3, and 4
      mm from the apex of the split-tooth model. Before obturations, a fine-medium
      System B plugger was prefitted 4 mm from the working length. The root canal
      system was obturated according to each of the experimental protocols. Resultant
      obturations (N = 10/protocol) were separated from the model, and replicated
      defects were assessed by a blinded evaluator who used an ordinal scale (0-4) that
      was based on how much each defect was replicated by GP. RESULTS: By using
      nonparametric analyses with Bonferroni adjustment (alpha = 0.01), with the apical
      2-mm defect, protocol D demonstrated significantly (P <= .01) better defect
      replication as compared with protocols A, B, and C. For the apical 3-mm defect,
      protocols B and D were significantly better (P <= .01) than protocols A and C.
      However, there was no difference (P > .01) between protocols with apical 4-mm
      defect (100% replication). CONCLUSIONS: The incremental down-pack with
      incremental backfill appears better able to replicate the most apical defect,
      which suggests benefits of repeated heat application and packing force to
      manipulate the GP in the apical plug area.

PMID- 23953295
TI  - Infection in a complex network of apical ramifications as the cause of persistent
      apical periodontitis: a case report.
AB  - INTRODUCTION: This article reports a case of persistent apical periodontitis
      lesion in a mesiobuccal root of a maxillary molar subjected to single-visit
      endodontic treatment. METHODS: The treatment protocol followed endodontic
      standards including using nickel-titanium instruments with working length ending
      0.5-mm short of the apex, establishment and maintenance of apical foramen
      patency, irrigation with 5% NaOCl, smear layer removal, a final rinse with and
      ultrasonic agitation of chlorhexidine, and filling by the vertical compaction
      technique. Even so, the lesion in the mesiobuccal root became larger in size
      after follow-up examination at 1 year 6 months, and periradicular surgery was
      performed. Radiographic control after 11 months showed that periradicular healing
      was almost complete. The root apex and the lesion were analyzed histologically
      and histobacteriologically. RESULTS: The lesion was diagnosed as a "pocket cyst,"
      and no bacteria were noted extraradicularly. The cause of continued disease was a
      heavy bacterial biofilm infection located in an intricate network of apical
      ramifications. Bacteria were also observed on the walls of one of the mesiobuccal
      canals packed between the obturation material and the root canal wall.
      CONCLUSIONS: This case report reinforces the need for treating the infected root
      canal as a complex system that possesses anatomic intricacies in which bacteria
      can spread and remain unaffected by treatment procedures.

PMID- 23953296
TI  - Misdiagnosis of a nasopalatine duct cyst: a case report.
AB  - INTRODUCTION: Nonendodontic lesions misdiagnosed as pathoses of endodontic origin
      are often referenced in the literature. One of the most frequent nonodontogenic
      cysts of the oral cavity, the nasopalatine duct cyst (NPDC), can be misdiagnosed
      as endodontic in nature. METHODS: A case is presented in which a patent NPDC was
      originally diagnosed as a sinus tract with subsequent endodontic nonsurgical
      retreatment and eventual extraction before endodontic consultation. RESULTS:
      After surgical treatment, a histopathologic diagnosis of an NPDC was confirmed.
      CONCLUSIONS: If diagnosed incorrectly, inappropriate endodontic treatment of a
      NPDC may be initiated to include unnecessary extraction. An increased
      understanding of anatomy, the use of appropriate diagnostic tests to include cone
      beam computed tomography imaging, and key examination techniques to distinguish
      endodontic lesions from nonendodontic pathoses are imperative for an accurate
      differential diagnosis and appropriate treatment outcome.

PMID- 23953297
TI  - Retrieval of extensive gutta-percha extruded into the maxillary sinus: use of 3
      dimensional cone-beam computed tomography.
AB  - INTRODUCTION: Close proximity of the maxillary sinus to the roots of maxillary
      teeth can predispose to the inadvertent deposition of endodontic products into
      the maxillary sinus. One such material is thermoplasticized injectable gutta
      percha, which has gained popularity of late. As a consequence of overfilling,
      some patients warrant surgical retrieval. METHODS: A case report of extreme
      overextension of gutta-percha within the maxillary sinus after endodontic
      retreatment on tooth #14 was provided. The distobuccal and palatal canals had
      been obturated with gutta-percha master cones and backfilled with
      thermoplasticized injectable warm gutta-percha. The mesiobuccal canal had only
      been filled with thermoplasticized injectable warm gutta-percha, the origin of
      the extrusion. Imagery with 3-dimensional cone-beam computed tomography was
      performed for localization of the gutta-percha. RESULTS: The patient underwent a
      Caldwell-Luc approach for removal of the extruded material. The gutta-percha was
      successfully removed intact, and the patient had an unremarkable postoperative
      course. However, the patient continues to have mild tenderness in the sinus
      region. CONCLUSIONS: The featured case exemplified the consequence of
      overinstrumentation and ensuing inadequate apical stop. In these situations, the
      obturation of a maxillary tooth with thermoplasticized injectable gutta-percha,
      without master cones, can potentially result in overfilling and deposition into
      the antrum. Use of 3-dimensional cone-beam computed tomography could enhance
      endodontic diagnosis, serve as an aid for visualization of foreign materials
      within the sinus and contiguous soft tissue structures, and improve clinical
      outcome.

PMID- 23953298
TI  - Evidence of the three main clonal Toxoplasma gondii lineages from wild mammalian
      carnivores in the UK.
AB  - Toxoplasma gondii is a zoonotic pathogen defined by three main clonal lineages
      (types I, II, III), of which type II is most common in Europe. Very few data
      exist on the prevalence and genotypes of T. gondii in the UK. Wildlife can act as
      sentinel species for T. gondii genotypes present in the environment, which may
      subsequently be transmitted to livestock and humans. DNA was extracted from
      tissue samples of wild British carnivores, including 99 ferrets, 83 red foxes, 70
      polecats, 65 mink, 64 badgers and 9 stoats. Parasite DNA was detected using a
      nested ITS1 PCR specific for T. gondii, PCR positive samples were subsequently
      genotyped using five PCR-RFLP markers. Toxoplasma gondii DNA was detected within
      all these mammal species and prevalence varied from 6.0 to 44.4% depending on the
      host. PCR-RFLP genotyping identified type II as the predominant lineage, but type
      III and type I alleles were also identified. No atypical or mixed genotypes were
      identified within these animals. This study demonstrates the presence of alleles
      for all three clonal lineages with potential for transmission to cats and
      livestock. This is the first DNA-based study of T. gondii prevalence and
      genotypes across a broad range of wild British carnivores.

PMID- 23953299
TI  - Contemporary experience with surgical treatment of aortic valve disease in
      children.
AB  - OBJECTIVES: Surgical treatment of aortic valve (AoV) disease in childhood
      involves complex decisions particularly in very small patients. There is no
      consensus regarding the optimum surgical option. The objective of this review was
      to analyze a contemporary experience of AoV surgery in a large children's
      hospital. METHODS: A retrospective review of children (aged <= 18 years)
      undergoing AoV repair or replacement from June 1995 to December 2011 was carried
      out. RESULTS: A total of 285 AoV operations (97 repairs, 188 replacements) were
      performed on 241 patients. Hospital survival for repair was 98% and for
      replacements was 97%. At follow-up of repairs, there were 16 (17%) reoperations
      and 3 (3%) late deaths. Follow-up of AoV replacements demonstrated 31 (16%)
      reoperations (homograft 27, autograft 3, mechanical 1) and 8 (4%) late deaths
      (homograft 5, autograft 2, mechanical 1). Freedom from reintervention or death
      (FRD) was found to be lower in repairs for infants (P = .048) and truncal valves
      (P < .05). For AoV replacements, infants and patients who had concomitant CHD or
      homografts (P < .0001) had lower FRD. Cox regression analysis for AoV
      replacements identified infants and homograft root replacements at a higher risk
      for death/reoperation. CONCLUSIONS: AoV repairs and replacements were generally
      found to be associated with low death and reoperation rates at long-term follow
      up. Infants had a lower freedom from reintervention or death after either an AoV
      repair or replacement, although truncal valve repairs and AoV replacement in
      patients with concomitant CHD were associated with lower valve survival. Among
      the valve options, homograft root replacement had a higher risk of
      death/reoperation and lowest freedom from reintervention or death.

PMID- 23953301
TI  - A proposal for a predictive model of paraplegia prevention during thoracic
      endovascular aortic repair.

PMID- 23953302
TI  - Intercostal artery reimplantation: a double-edged sword.

PMID- 23953303
TI  - Twilight of the gods.

PMID- 23953304
TI  - Is segmentectomy suitable for solid-type lung cancer?

PMID- 23953305
TI  - Reply to the editor.

PMID- 23953306
TI  - Reply to the editor.

PMID- 23953307
TI  - The effectiveness of simplified frozen elephant trunk repair for acute Debakey
      type I dissection.

PMID- 23953308
TI  - Clinical evidence from randomized trials, network meta-analyses, and conflicts of
      interests.

PMID- 23953309
TI  - Reply to the editor.

PMID- 23953310
TI  - Gender disparity may contribute to the quasi preservation of cardioprotection by
      remote preconditioning with isoflurane but not propofol in CABG.

PMID- 23953311
TI  - Reply to the editor.

PMID- 23953312
TI  - Reply to the editor.

PMID- 23953313
TI  - Avoiding tracheostomy complication.

PMID- 23953314
TI  - Clamp times, teaching, and technical excellence.

PMID- 23953315
TI  - Reply to the editor.

PMID- 23953316
TI  - [Nerve stimulation is not obsolete yet: reply].

PMID- 23953317
TI  - Delirium in older people after proximal femoral fracture repair: role of a
      preoperative screening cognitive test.
AB  - OBJECTIVE: Preoperative cognitive impairment has been identified as a major risk
      factor for postoperative delirium in older people. The aim of this study was to
      evaluate whether a validated and rapid screening cognitive test - COgnitive
      Disorder EXamination (CODEX) - performed preoperatively before proximal femoral
      fracture repair, was associated with a risk of postoperative delirium. STUDY
      DESIGN: We performed an observational prospective cohort study in orthopedic
      surgery department of a French hospital. PATIENTS: We included patients aged
      70years or older undergoing proximal femoral fracture repair and who were free of
      known dementia and delirium at the preoperative phase. METHODS: Before surgery,
      the anesthesiologist realized the CODEX based on three-word recall test,
      simplified clock drawing and if one of these tasks was abnormal, spatial
      orientation was assessed. Delirium was routinely sought on postoperative day 3
      (D3) using the Confusion Assessment Method by the geriatrician. RESULTS: Among
      the 52 included patients, seven (13.5%) had delirium on D3. All seven patients
      were among the 25 patients with abnormal CODEX results. None of the 27 patients
      with normal CODEX results had postoperative delirium. Abnormal CODEX was
      significantly associated with the risk of postoperative delirium in univariate
      analysis and after adjustment for age (odds ratio [OR]: 13.33; 95% confidence
      interval, [95%CI]: 1.85+/-infinity; P<0.003). CONCLUSION: Abnormal preoperative
      rapid screening test CODEX is independently associated with postoperative
      delirium in older people undergoing hip fracture surgery and free of known
      dementia.

PMID- 23953318
TI  - [Postoperative pain management after caesarean section in Kigali University
      Medical Center: first use of intrathecal morphine].

PMID- 23953319
TI  - [Usefulness of Bispectral Index (BIS) monitoring for early detection of cerebral
      hypoperfusions].
AB  - OBJECTIVES: The goal of the study was to assess whether clinically significant
      cerebral hypoperfusion in awake patients would be associated with some
      alterations in the values of the bispectral index (BIS) monitoring. STUDY DESIGN:
      Observational study. POPULATION AND METHODS: We monitored the BIS during
      endovascular carotid artery occlusion testing in awake patients. RESULTS: Twenty
      eight patients were included. Twenty-one adequately tolerated the procedure.
      Their BIS value remained stable throughout the procedure. Four patients had poor
      angiographic tolerance, but no clinical symptoms. Their BIS value slightly
      decreased during the test (minimal BIS: 83 [79-87]). Three patients had poor
      clinical and angiographic tolerance of the occlusion. They all experienced an
      immediate and dramatic decrease in their BIS value (minimal BIS: ipsilateral to
      clamping: 50 [45-60]; contralateral to clamping: 48 [45-52]). In all patients,
      the clinical symptoms and the BIS normalized after deflating the occlusion
      balloon. CONCLUSION: In awake patients, the observed values of the BIS monitoring
      seem to be associated with clinically relevant cerebral hypoperfusion.

PMID- 23953320
TI  - [Pneumocephalus following a blood patch with saline loss of resistance technique:
      is there a take-home message?].

PMID- 23953321
TI  - [Abdominal-pelvis impalement: an uncommon accident].

PMID- 23953322
TI  - An effective dose of ketamine for eliminating pain during injection of propofol:
      a dose response study.
AB  - BACKGROUND AND PURPOSE: Ketamine can completely eliminate pain associated with
      propofol injection. However, the effective dose of ketamine to eliminate propofol
      injection pain has not been determined. The purpose of this study was to
      determine the effective dose of ketamine needed to eliminate pain in 50% and 95%
      of patients (ED50 and ED95, respectively) during propofol injections. METHODS:
      This study was conducted in a double-blinded fashion and included 50 patients
      scheduled for elective gynecological laparoscopy under general anesthesia. The
      initial dose of ketamine used in the first patient was 0.25mg/kg. The dosing
      modifications were in increments or decrements of 0.025 mg/kg. Ketamine was
      administered 15 seconds before injecting propofol (2.5mg/kg), which was injected
      at a rate of 1mL/s. Patients were asked to rate their pain during propofol
      injection every 5s econds using a 0-3 pain scale. The highest pain score was
      recorded. The ED50, ED95 and 95% confidence intervals (CI) were determined by
      probit analyses. RESULTS: The dose of ketamine ranged from 0.175 to 0.275 mg/kg.
      The ED50 and ED95 of ketamine for eliminating pain during propofol injection were
      0.227 mg/kg and 0.283 mg/kg, respectively (95%CI: 0.211-0.243 mg/kg and 0.26
      0.364 mg/kg, respectively). CONCLUSION: Ketamine at an approximate dose of
      0.3mg/kg was effective in eliminating pain during propofol injection.

PMID- 23953323
TI  - Laparoscopy with laparotenser in awake patients with subcostal bilateral
      transversus abdominis plane block and lumbar subarachnoid anesthesia: initial
      report of three cases. A new frontier in day surgery?

PMID- 23953324
TI  - Establishment and molecular mechanisms of HIV-1 latency in T cells.
AB  - Treatment of an HIV infected individual with antiretroviral drugs is a successful
      way to suppress the plasma viral RNA load below the limit of detection (50 copies
      HIV RNA/ml plasma). This can provide lifelong protection against virus-induced
      pathogenesis in drug-adherent patients. Unfortunately, even after many years of
      continuous treatment, the virus persists and the plasma viral load will rebound
      rapidly when therapy is interrupted. The reason for this rapid rebound is the
      presence of a long-lived reservoir of latent HIV-1 proviruses that can be
      reactivated in resting memory T cells. Attempts to eliminate these proviruses
      have thus far not been successful and this long-lived latent reservoir is
      therefore considered a major obstacle toward a cure for HIV-1. A detailed
      understanding of the molecular mechanisms causing HIV latency and knowledge on
      the establishment of this reservoir may give us clues for future strategies
      aiming at the eradication of this reservoir. 

PMID- 23953325
TI  - Evaluation of cryopreserved ovarian tissue from prepubertal patients after long
      term xenografting and exogenous stimulation.
AB  - OBJECTIVE: To assess follicular development after long-term xenotransplantation
      and exogenous stimulation of cryopreserved prepubertal ovarian tissue. DESIGN:
      Pilot study. SETTING: Gynecology research unit in a university hospital.
      PATIENT(S): Cryopreserved ovarian fragments were obtained from five prepubertal
      patients aged 7.2-12.2 years. INTERVENTION(S): Xenografting of frozen-thawed
      prepubertal ovarian fragments to SCID mice for 5 months and exogenous
      stimulation. MAIN OUTCOME MEASURE(S): Follicular density, morphology,
      proliferation, development. RESULT(S): Follicular density varied between 1.05 and
      47.89 follicles/mm(2) in frozen-thawed ovarian tissue and 0.48 and 32.74
      follicles/mm(2) in grafted prepubertal ovarian tissue. Growing follicles at the
      last stage of follicular development were observed at significantly higher
      proportions after grafting. No statistical difference was evidenced in the number
      of primordial follicles, representing the largest proportion of the follicle pool
      (99.51% before grafting and 92.46% after grafting). Ki67 and antimullerian
      hormone expression were observed in these growing follicles. CONCLUSION(S): This
      is the first description of transplantation of human cryopreserved prepubertal
      ovarian tissue to mice, demonstrating that a very high number of follicles
      survive after transplantation and a large pool of primordial follicles remains
      dormant. Growing follicles were observed, proving the responsiveness of
      prepubertal ovarian tissue to gonadotropins.

PMID- 23953326
TI  - What do reproductive-age women who undergo oocyte cryopreservation think about
      the process as a means to preserve fertility?
AB  - OBJECTIVE: To better understand women's beliefs, priorities, and attitudes toward
      oocyte cryopreservation, to appreciate the extent of their reproductive
      education, and to track the reproductive paths of women who chose to undergo
      oocyte cryopreservation treatment. DESIGN: An anonymous 30-question survey.
      SETTING: Not applicable. PATIENT(S): From 2005-2011, 478 women completed >=1
      oocyte cryopreservation treatment cycle at our center to defer reproduction.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Demographics, motivations,
      desires, fertility knowledge, and outcomes related to oocyte cryopreservation.
      RESULT(S): A total of 183 patients (38%) completed the survey with >80% being
      aged >=35 years; white; having no partner at time of oocyte cryopreservation;
      undergoing oocyte cryopreservation after an optimal reproductive age; feeling
      they had improved their reproductive future after oocyte cryopreservation and
      being empowered by the process; aware of age-related infertility; sensing popular
      media falsely portrayed the upper age limit for natural conception; and recorded
      lack of partner as the primary rationale for not yet starting a family. Nineteen
      percent of respondents added that workplace inflexibility contributed to their
      reproductive dilemma. Half stated they learned about oocyte cryopreservation from
      a friend; others became aware through a medical provider, the media, and the
      internet. Most patients (93%) have not yet returned to use their frozen oocytes;
      11 stated they had. Overall, 20% reported a successful conception after oocyte
      cryopreservation. CONCLUSION(S): Surveying oocyte cryopreservation patients
      provides a glimpse into the knowledge base and motivations surrounding current
      female reproductive practices. Oocyte cryopreservation technology may prove to
      bridge the gap between reproductive prime and when a woman is realistically
      "ready" to have children.

PMID- 23953327
TI  - Continuous versus cyclic use of oral contraceptives after surgery for symptomatic
      endometriosis: a prospective cohort study.
AB  - OBJECTIVE: To evaluate the efficacy of continuous oral contraceptive (OC) use
      versus the usual cyclic fashion in the recurrence of endometriosis-related
      symptoms after surgery. DESIGN: Prospective cohort trial involving patients in
      two tertiary care units. SETTING: Academic institution in collaboration with a
      private hospital. PATIENT(S): 356 patients underwent surgical treatment by
      laparoscopy for symptomatic endometriosis. INTERVENTION(S): After surgical
      treatment for endometriosis, patients offered 6-month course of cyclic OC
      (including a 7-day pill-free period) or continuous OC. MAIN OUTCOME MEASURE(S):
      Recurrence rate of endometriosis-related symptoms and endometriomas after
      fertility-sparing surgery. RESULT(S): Out of 356 patients, 167 were placed on the
      usual cyclic OC course and 85 on continuous OC for a minimum of 6 months. The
      continuous OC group experienced a statistically significant reduction in
      recurrence rates for endometrioma, dysmenorrhea, and non-menstrual pelvic pain as
      compared with the cyclic OC group. There was no reduction in the recurrence of
      dyspareunia between the two groups. CONCLUSION(S): After surgical treatment of
      endometriosis, the use of both cyclic and continuous OC improves pain symptoms
      when compared with preoperative scores. Continuous OC appears to be associated
      with a reduced recurrence rate for dysmenorrhea, non-menstrual pelvic pain, and
      endometrioma but not for dyspareunia as compared with cyclic OC.

PMID- 23953329
TI  - ETS for primary hyperhidrosis--markers of success.

PMID- 23953328
TI  - Multidrug-resistant transport activity protects oocytes from chemotherapeutic
      agents and changes during oocyte maturation.
AB  - OBJECTIVE: To determine the multidrug-resistant transporter (MDR) activity in
      oocytes and their potential role in oocyte susceptibility to chemotherapy.
      DESIGN: Experimental laboratory study. SETTING: University and academic center
      for reproductive medicine. SUBJECT(S): Women with eggs retrieved for
      intracytoplasmic sperm injection cycles and adult female FVBN and B6C3F1 mouse
      strains. INTERVENTION(S): Inhibition of MDR activity in oocytes. MAIN OUTCOME
      MEASURE(S): Efflux activity of MDRs with the use of quantitative fluorescent dye
      efflux, and oocyte cell death when exposed to chemotherapy. RESULT(S): Oocytes
      effluxed fluorescent reporters, and this activity was significantly reduced in
      the presence of the MDR inhibitor PSC 833. Geminal vesicle oocytes were more
      efficient at efflux than metaphase 2 oocytes. Human oocytes exposed to
      cyclophosphamide and PSC 833 showed cell death with the use of two different
      viability assays compared with control samples and those exposed to
      cyclophosphamide alone. Immunoblots detected MDR-1 in all oocytes, with the
      greatest accumulation in the geminal vesicle stage. CONCLUSION(S): Oocytes have a
      vast repertoire of active MDRs. The implications of this study are that these
      protective mechanisms are important during oogenesis and that these activities
      change with maturation, increasing susceptibility to toxicants. Future directions
      may exploit the up-regulation of these transporters during gonadotoxic therapy.

PMID- 23953330
TI  - A systematic review and meta-analysis of lower limb neuromuscular alterations
      associated with knee osteoarthritis during level walking.
AB  - BACKGROUND: Neuromuscular alterations are increasingly reported in individuals
      with knee osteoarthritis (KOA) during level walking. We aimed to determine which
      neuromuscular alterations are consistent in KOA individuals and how these may be
      influenced by osteoarthritis severity, varus alignment and/or joint laxity.
      METHODS: Electronic databases were searched up to July 2012. Cross-sectional
      observational studies comparing lower-limb neuromuscular activity in individuals
      with KOA, healthy controls or with different KOA cohorts were included. Two
      reviewers assessed methodological quality. Effect sizes were used to quantify the
      magnitude of observed differences. Where studies were homogenous, effect sizes
      were pooled using a fixed-effects model. FINDINGS: Fourteen studies examining
      neuromuscular alterations in indices of co-contraction, muscle amplitude and
      muscle activity duration were included. Data pooling revealed that moderate KOA
      individuals exhibit increased co-contraction of lateral knee muscles (ES 0.64
      [0.3 to 0.97]) and moderately increased rectus femoris (ES 0.73 [0.23 to 1.22]),
      vastus lateralis (ES 0.77 [0.27 to 1.27]) and biceps femoris (ES 1.18 [0.67 to
      1.7]) mean amplitude. Non-pooled data indicated prolonged activity of these
      muscles. Increased medial knee neuromuscular activity was prevalent for those
      exhibiting varus alignment and medial knee joint laxity. Interpretation
      Individuals with KOA exhibited increased co-contraction, amplitude and duration
      of lateral knee muscles regardless of disease severity, limb alignment or medial
      joint laxity. Individuals with severe disease, varus alignment and medial joint
      laxity demonstrate up-regulation of medial knee muscles. Future research
      investigating the efficacy of neuromuscular rehabilitation programs should
      consider the effect of simultaneous up-regulation of medial and lateral knee
      muscles on disease progression.

PMID- 23953331
TI  - A numerical study to analyse the risk for pressure ulcer development on a spine
      board.
AB  - BACKGROUND: Spine boards are used to immobilise accident victims suspected of
      having spinal injury. Guidelines about the maximum time patients remain on the
      board are often exceeded and on occasions may lead to pressure ulcers.
      Etiological research has shown that two processes ultimately lead to pressure
      ulcers:"Ischemic damage" which takes several hours to initiate and "deformation
      damage" at high strains. The latter process is very quick and the first signs of
      cell damage are already evident within minutes. Thus in order to minimise the
      risk of pressure ulcer development during prolonged loading, a new soft-layered
      long spine board has been designed. METHODS: A subject specific numerical
      approach has been adopted to evaluate the prototype spine board in comparison to
      a conventional spine board, with reference to the estimated strains in the soft
      tissues adjacent to the sacrum in the supine position. The model geometry is
      derived from magnetic resonance images of three human volunteers in an unloaded
      situation. The loaded images are used to "tune" the material parameters of skin,
      fat and muscle. The prediction of the deformed contours on the soft-layered board
      is used to validate the model. FINDINGS: Comparison of the internal strains in
      muscle tissue near the spine showed that internal strains on the soft-layered
      board are reduced and maximum strains are considerably less than the threshold at
      which deformation damage is possible. By contrast, on the rigid spine board this
      threshold is exceeded in all cases. INTERPRETATION: The prototype comfort board
      is able to reduce the risk for deformation damage and thus reduces the risk of
      developing pressure ulcers.

PMID- 23953332
TI  - Neuroanatomical deficits in drug-naive adult patients with generalized social
      anxiety disorder: a voxel-based morphometry study.
AB  - Little is known, so far, about the cerebral structural deficits in drug-naive
      adult social anxiety disorder (SAD) patients. The present study aimed to explore
      the cerebral anatomic deficits in drug-naive adult generalized SAD patients using
      voxel-based morphometric analysis with DARTEL. High-resolution T1-weighted images
      were acquired from 20 drug-naive adult SAD patients and 19 age-, sex- and
      education-matched controls. The volumes of gray matter, white matter,
      cerebrospinal fluid, and total intracranial volume were compared between groups
      using two-sample t-tests with age and gender as covariates. Gray matter density
      (GMD) was compared between groups using voxel-wise two-sample t-test analysis.
      Correlation analysis was used to identify any associations between regional GMD
      and clinical symptoms. Compared with healthy controls, SAD patients showed
      significantly lower GMD in the bilateral thalami, right amygdala, and right
      precuneus. Furthermore, the GMD in the right amygdala was negatively related to
      the disease duration, but positively correlated with age of onset. Our findings
      demonstrated that cerebral anatomic deficits could be found within limbic and
      thalamic areas in drug-naive SAD patients, which provides structural information
      to complement the functional alterations observed in the same regions. 

PMID- 23953333
TI  - Evoked pressure curves from the external anal sphincter following transcranial
      magnetic stimulation in healthy volunteers and patients with faecal incontinence.
AB  - AIM: The hypothesis was tested that evoked pressure curves (EPCs) after
      transcranial magnetic stimulation (TMS) would provide additional
      neuropathophysiological information on the descending pathways to the external
      anal sphincter (EAS) in patients with faecal incontinence (FI). METHOD: Twenty
      five healthy subjects and 69 patients with FI were investigated. TMS was applied
      to the vertex, and EPCs were recorded with a probe placed through the EAS. TMS
      was performed with the EAS at rest and during contraction (facilitated
      responses). At least three responses were recorded for each modality. Clinical
      data and anorectal manometric, electrophysiological perineal and transanal
      ultrasound recordings were compared with respect to the EPC results. RESULTS:
      There was no statistically significant difference between the EPCs of healthy
      subjects and FI patients. Twenty-three per cent of the FI patients had abnormal
      EPC latencies, with significantly lower voluntary contraction amplitudes (P =
      0.03) and significantly higher rectal sensation (P = 0.04) than the other group.
      We found no significant difference between FI patients with and without abnormal
      EPC latencies in terms of clinical characteristics and electrophysiological and
      endoanal ultrasound parameters. There was no difference in the identified causes
      of the FI between the two groups. CONCLUSION: As abnormal EPC latencies were
      found in 23% of FI patients with no known central neurological disease, abnormal
      EPC latencies might reveal undetected lesions of descending pathways in patients
      with FI.

PMID- 23953335
TI  - Consultative hematology: introduction.

PMID- 23953334
TI  - A 50-year journey to cure childhood acute lymphoblastic leukemia.
AB  - The 50th anniversary of Seminars in Hematology coincides with the 50th
      anniversary of St. Jude Children's Research Hospital, and both milestones are
      inexorably linked to studies contributing to the cure of childhood acute
      lymphoblastic leukemia (ALL). We thought it fitting, therefore, to mark these
      events by traveling back in time to point out some of the achievements,
      institutions, study groups, and individuals that have made cure of childhood ALL
      a reality. In many instances, progress was driven by new ideas, while in others
      it was driven by new experimental tools that allowed more precise assessment of
      the biology of leukemic blasts and their utility in selecting therapy. We also
      discuss a number of contemporary advances that point the way to exciting future
      directions. Whatever pathways are taken, a clear challenge will be to use
      emerging genome-based or immunologic-based treatment options in ways that will
      enhance, rather than duplicate or compromise, recent gains in outcome with
      classic cytotoxic chemotherapy. The theme of this journey serves as a reminder of
      the chief ingredient of any research directed to a catastrophic disease such as
      ALL. It is the audacity of a small group of investigators who confronted a
      childhood cancer with the goal of cure, not palliation, as their mindset. 

PMID- 23953337
TI  - Hematologic manifestations of kidney disease.
AB  - Physiologically, there is an intimate link between the kidney and the blood. Many
      of the kidney diseases are the result of alteration in the blood such as
      dysproteinemia, microangiopathic hemolytic anemia (MAHA), hemolysis, etc. On the
      other hand, the kidney is the organ responsible for the regulation of
      hematopoiesis. Renal dysfunction can lead to both anemia and polycythemia. In
      addition, recent understanding of the MAHA process reveals that the renal
      microvasculature plays a key role in the pathogenesis. Finally, the failure of
      the kidney to clear toxins from the body can result in alteration involving
      hemostasis, as well as leukocyte function and survival. 

PMID- 23953336
TI  - Evaluation and management of patients with isolated neutropenia.
AB  - Neutropenia, defined as an absolute neutrophil count (ANC) <1.5 * 10(9)/L,
      encompasses a wide range of diagnoses, from normal variants to life-threatening
      acquired and congenital disorders. This review addresses the diagnosis and
      management of isolated neutropenia, not multiple cytopenias due to splenomegaly,
      bone marrow replacement, or myelosuppression by chemotherapy or radiation.
      Laboratory evaluation generally includes repeat complete blood cell counts (CBCs)
      with differentials and bone marrow examination with cytogenetics. Neutrophil
      antibody testing may be useful but only in the context of clinical and bone
      marrow findings. The discovery of genes responsible for congenital neutropenias
      now permits genetic diagnosis in many cases. Management of severe chronic
      neutropenia includes commonsense precautions to avoid infection, aggressive
      treatment of bacterial or fungal infections, and administration of granulocyte
      colony-stimulating factor (G-CSF). Patients with severe chronic neutropenia,
      particularly those who respond poorly to G-CSF, have a risk of eventually
      developing myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) and
      require monitoring for this complication, which also can occur without G-CSF
      therapy. Patients with cyclic, idiopathic, and autoimmune neutropenia have
      virtually no risk of evolving to MDS or AML. Hematopoietic stem cell
      transplantation is a curative therapy for congenital neutropenia with MDS/AML or
      with cytogenetic abnormalities indicating impending conversion. 

PMID- 23953338
TI  - Hematologic manifestations of liver disease.
AB  - The liver plays a key role in both protein biosynthesis and lipid metabolism. As
      a result, hepatic synthetic dysfunction can have adverse effects on both cellular
      and soluble components of blood. Anemia may occur due to the hemolysis of
      acanthocytes (spur cells), which is ultimately due to abnormal lipid composition
      of the red blood cell membrane. Thrombocytopenia may result from several
      different mechanisms. Cytopenias also may be a consequence of hypersplenism. The
      liver is the primary site for synthesis of most procoagulant and anticoagulant
      proteins. The coagulopathy of liver disease is therefore complex. Early in the
      course of liver disease, thrombocytopenia and a coagulopathy associated with a
      prothrombotic state are not uncommon, whereas with more advanced disease
      pancytopenia and coagulopathy associated with hemorrhage become manifest. Fresh
      frozen plasma and adjuncts to hemostasis may be used as temporizing measures in
      bleeding patients. However, definitive management of many of the defects due to
      fulminant hepatic failure requires liver transplantation. 

PMID- 23953339
TI  - Hematologic complications of pregnancy.
AB  - Pregnancy induces a number of physiologic changes that affect the hematologic
      indices, either directly or indirectly. Recognizing and treating hematologic
      disorders that occur during pregnancy is difficult owing to the paucity of
      evidence available to guide consultants. This review discusses specifically the
      diagnosis and management of benign hematologic disorders occurring during
      pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic
      complication and is easily treated with oral iron formulations; however, care
      must be taken not to miss other causes of anemia, such as sickle cell disease.
      Thrombocytopenia is also a common reason for consulting the hematologist, and
      distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP),
      preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low
      platelets), or thrombotic thrombocytopenic purpura (TTP) is essential since the
      treatment differs widely. Occasionally the management of mother and infant
      involves the expeditious recognition of neonatal alloimmune thrombocytopenia
      (NAIT), a condition that is responsible for severe life-threatening bleeding of
      the newborn. Additionally, inherited and acquired bleeding disorders affect
      pregnant women disproportionately and often require careful monitoring of
      coagulation parameters to prevent bleeding in the puerperium. Finally, venous
      thromboembolism (VTE) during pregnancy is still largely responsible for mortality
      during pregnancy, and the diagnosis, treatment options and guidelines for
      prevention of VTE during pregnancy are explored. 

PMID- 23953340
TI  - Anemia of chronic disease.
AB  - Anemia of chronic disease (ACD) or inflammation may be secondary to infections,
      autoimmune disorders, chronic renal failure, or malignancies. It is characterized
      by an immune activation with an increase in inflammatory cytokines and resultant
      increase in hepcidin levels. In addition, inappropriate erythropoietin levels or
      hyporesponsiveness to erythropoietin and reduced red blood cell survival
      contribute to the anemia. Hepcidin being the central regulator of iron metabolism
      plays a key role in the pathophysiology of ACD. Hepcidin binds to the iron export
      protein, ferroportin, present on macrophages, hepatocytes, and enterocytes,
      causing degradation of the latter. This leads to iron trapping within the
      macrophages and hepatocytes, resulting in functional iron deficiency. Production
      of hepcidin is in turn regulated by iron stores, inflammation, and erythropoiesis
      via the BMP-SMAD and JAK-STAT signaling pathways. Treatment of anemia should
      primarily be directed at the underlying disease, and conventional therapy such as
      red blood cell transfusions, iron, erythropoietin, and novel agents targeting the
      hepcidin-ferroportin axis and signaling pathways (BMP-SMAD, JAK-STAT) involved in
      hepcidin production also may be considered. 

PMID- 23953341
TI  - Thrombocytopenia in the intensive care unit-diagnostic approach and management.
AB  - Thrombocytopenia often complicates critical illness and is associated with
      increased morbidity and mortality. Approaching thrombocytopenia is challenging in
      the intensive care unit (ICU) because of the multifactorial pathogenesis of this
      disorder. Interpretation of the platelet count course after ICU admission is
      helpful to narrow down the cause of thrombocytopenia. Whereas a moderate decrease
      within the first 3 days is rather typical in severely ill patients, an absent or
      blunted platelet count increase after 5 days indicates continuing critical
      illness and a worse outcome. A rapid decrease in platelet counts of more than 50%
      within 1-2 days, especially if occurring after an intermittent rise, requires
      immediate attention as it may be a symptom of immune-mediated mechanisms, eg,
      heparin-induced thrombocytopenia. Treatment should target the underlying disease.
      Platelet transfusions are indicated in bleeding patients, while there is no
      strong evidence supporting the usefulness of prophylactic transfusions in ICU
      patients. 

PMID- 23953342
TI  - Review of the American College of Chest Physicians 2012 Guidelines for
      Anticoagulation Therapy and Prevention of Thrombosis.
AB  - The eighth edition (AT8) of the American College of Chest Physicians (ACCP)
      Antithrombotic Therapy and Prevention of Thrombosis Guideline, published in June
      2008, was a comprehensive presentation of primary studies and detailed
      discussions of rationale for recommendations. This resulted in an approximately
      900-page Chest Supplement publication. Updating the guidelines in a succinct
      fashion posed a formidable challenge for the ninth edition (AT9), published in
      February 2012. The strategy adopted for AT9 was to publish an Executive Summary
      of the recommendations in a 50-page document in the Chest supplement highlighting
      the changes, with online publication of the full version. Major innovative
      changes include a recognition of the value of estimating the risk reductions in
      symptomatic, as opposed to asymptomatic (venographically), detected venous
      thrombosis, using nonconflicted methodologists as topic editors, new insights
      into evidence, and increasing emphasis on what is known about patients' values
      and preferences that have served to improve this edition of the guidelines. This
      review provides a summary of the updates of the guidelines for anticoagulation
      therapy and prevention of thrombosis. The AT9 recommendations are presented with,
      if included, the AT8 recommendations in parenthesis for comparison purposes. 

PMID- 23953343
TI  - Trauma-induced coagulopathy: from biology to therapy.
AB  - Trauma is a leading cause of death and disability. Hemorrhage is the major
      mechanism responsible for death during the first 24 hours following trauma. One
      quarter of severely injured patients present in the emergency room with acute
      coagulopathy of trauma and shock (ACOT). The drivers of ACOT are tissue
      hypoperfusion, inflammation, and activation of the neurohumoral system. ACOT is a
      result of protein C activation with cleavage of activated factor VIII and V and
      inhibition of plasminogen activator inhibitor-1 (PAI-1). The resuscitation
      associated coagulopathy (RAC) is secondary to a combination of acidosis,
      hypothermia and dilution from intravenous blood and fluid therapy. RAC may
      further aggravate acidosis and hypoxia resulting in a vicious cycle. This review
      focuses on the biology of the trauma-associated coagulopathy, and reviews current
      therapeutic strategies. 

PMID- 23953344
TI  - Oxidative stress and immune thrombocytopenia.
AB  - Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by
      increased platelet destruction or decreased platelet production. The mechanism of
      the disease has been extensively studied so that we now have a much improved
      understanding of the pathophysiology; however, the trigger of the autoimmunity
      remains unclear. More recently, oxidative stress was identified to be involved in
      the pathogenesis of ITP and provides a new hypothesis for the initiation of
      autoimmunity in patients with ITP. In this review, oxidative stress and its
      impact on autoimmunity, particularly ITP, will be covered. 

PMID- 23953345
TI  - An older origin for the Acheulean at Melka Kunture (Upper Awash, Ethiopia):
      techno-economic behaviours at Garba IVD.
AB  - In the 1970s and 1980s, the emergence of the Acheulean at Melka Kunture (Upper
      Awash, Ethiopia) was dated to 1 Ma (million years ago), based on the typo
      metrical analysis of the lithic assemblage of Garba XIIJ. Older sites such as
      Gombore I, Karre I, and Garba IV (1.7-1.5 Ma) were classified as
      Oldowan/Developed Oldowan. Consequently, the Oldowan and the Acheulean at Melka
      Kunture were interpreted as two distinct technologies separated by a
      chronological gap of 0.5 Ma. The archaeostratigraphic unit D of Garba IV, dated
      to ~1.5 Ma, yielded one of the richest Early Stone Age lithic series in East
      Africa. In this paper, a review traces methods of technological analysis, based
      on the concept of chaine operatoire, to update our knowledge of the techno
      economic behaviours at this site. The results show two major elements
      characteristic of cultural changes in the Melka Kunture sequence: (1) the
      emergence of a new chaine operatoire focused on large flake/large cutting tool
      (LCT) production, and (2) a large variability of small debitage modalities with
      systematic preparation of the striking platform and the appearance of a certain
      degree of predetermination. These technological traits are shared by the
      contemporaneous sites in East Africa and are considered to be typical of the
      early Acheulean. This suggests an older origin for the Acheulean at Melka
      Kunture, 0.5 Ma than previously inferred.

PMID- 23953346
TI  - Comparative pharmacokinetics study after oral administration of geniposide in
      normal rats and adjuvant-induced arthritis rats by UPLC-MS/MS.
AB  - A simple and rapid ultra-performance liquid chromatography-electrospray
      ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method for quantitative
      analysis of geniposide (GE) in rat plasma was developed, validated and applied to
      determine the level of GE in rat plasma after oral administration of GE in
      adjuvant-induced arthritis (AA) and normal rats. The investigation showed that
      there were significant differences in the groups between the normal rat and AA
      rat in pharmacokinetics parameters, such as the area under the time versus drug
      concentration curve (AUC(0-infinity)) (3.77 +/- 0.68 versus 2.27 +/- 0.42, p <
      0.05), the apparent volume of distribution (V) (140.41 +/- 2.07 versus 136.51 +/-
      1.03, p < 0.05), the mean residence time (MRT) (3.98 +/- 0.90 versus 3.80 +/-
      0.50, p < 0.05) and the clearance from the total body (CL) (16.10 +/- 2.87 versus
      26.44 +/- 4.94, p < 0.05). The results indicated that AA could alter the
      pharmacokinetics of the drug and these experimental findings could be useful for
      the further study of the clinical applications of GE.

PMID- 23953347
TI  - Genetic architecture of the pro-inflammatory state in an extended twin-family
      design.
AB  - In this study we examined the genetic architecture of variation in the pro
      inflammatory state, using an extended twin-family design. Within the Netherlands
      Twin Register Biobank, fasting Tumor Necrosis Factor-alpha (TNF-alpha),
      Interleukin-6 (IL-6), C-Reactive Protein (CRP), and fibrinogen levels were
      available for 3,534 twins, 1,568 of their non-twin siblings, and 2,227 parents
      from 3,095 families. Heritability analyses took into account the effects of
      current and recent illness, anti-inflammatory medication, female sex hormone
      status, age, sex, body mass index, smoking status, month of data collection, and
      batch processing. Moderate broad-sense heritability was found for all
      inflammatory parameters (39%, 21%, 45%, and 46% for TNF-alpha, IL-6, CRP and
      fibrinogen, respectively). For all parameters, the remaining variance was
      explained by unique environmental influences and not by environment shared by
      family members. There was no resemblance between spouses for any of the
      inflammatory parameters, except for fibrinogen. Also, there was no evidence for
      twin-specific effects. A considerable part of genetic variation was explained by
      non-additive genetic effects for TNF-alpha, CRP, and fibrinogen. For IL-6, all
      genetic variance was additive. This study may have implications for future genome
      wide association studies by setting a clear numerical target for genome-wide
      screens that aim to find genetic variants regulating the levels of these pro
      inflammatory markers. 

PMID- 23953348
TI  - Androgen and androgen-metabolizing enzymes in metastasized lymph nodes of breast
      cancer.
AB  - Androgen receptor and androgen metabolizing enzymes, 17beta-hydroxysteroid
      dehydrogenase type 5 (17betaHSD5) and 5alpha-reductase1 (5alpha1), are frequently
      detected in primary tumor of breast cancer, but their status in metastatic lymph
      nodes has not been examined. The biological role of androgen in breast cancer and
      its metastatic process also remain unknown. In this study, we used
      immunohistochemistry to localize the expression of androgen receptor, 17betaHSD5,
      and 5alpha1 in primary tumors and paired metastatic lymph nodes and correlated
      the findings with clinicopathologic factors of individual patients. Approximately
      70% of primary tumors and paired metastatic lymph nodes expressed androgen
      receptor, with significant correlation between both lesions. However, 17betaHSD5
      and 5alpha1 immunoreactivity was decreased in metastatic lymph nodes. Alone or in
      tandem with androgen receptor, 5alpha1 was associated with significantly lower Ki
      67 index, lower pathologic grade, and higher estrogen receptor positivity, but
      androgen receptor/5alpha1 double positivity in lymph nodes was associated with
      larger lymph node metastasis and higher TNM stage. In conclusion, androgen
      receptor immunoreactivity remained stable during the process of metastasis,
      whereas androgen-metabolizing enzymes decreased. Although results of our study
      and previous reports imply additional roles of androgen metabolism in the
      metastasis process, especially conversion by 5alpha1, there may be divergence
      between its effects on primary tumor and those in metastatic lymph nodes. 

PMID- 23953349
TI  - Prevalence and co-occurrence of parentally reported possible asthma and allergic
      manifestations in pre-school children.
AB  - BACKGROUND: The aim of this study was to make an in-depth analysis of the
      prevalence and co-occurrence in pre-school children of possible asthma and atopic
      manifestations. METHODS: In Sweden 74%-84% of preschool children, depending on
      age, attend municipality organised day-care centres. Parents of 5,886 children 1
      6 years of age, sampled from day-care centres in 62 municipalities all over
      Sweden, responded to a postal questionnaire regarding symptoms indicating
      prevalent possible asthma, allergic rhinitis, eczema, and food, furred pet and
      pollen allergy and other data in their children. Possible asthma was defined as
      any of the four criteria wheezing four times or more during the last year,
      physician diagnosis and current wheezing, ever had asthma and current wheezing,
      and current use of inhalation steroids, all based on questionnaire responses.
      RESULTS: The overall prevalence of possible asthma was 8.9%, of eczema 21.7%, of
      rhinitis 8.1%, and of food allergy 6.6%. There was a highly significant co
      occurrence between possible asthma and all atopic manifestations, 35.7% having
      any of the manifestations. Presence of pet allergy was the manifestation showing
      the closest co-occurrence with presence of possible asthma, presence of pollen
      allergy with presence of rhinitis, and presence of food allergy with presence of
      eczema. Assessed from plots of age-specific prevalence of possible asthma,
      rhinitis, eczema and food allergy, the prevalence of all manifestations increased
      from one to three years of age and then decreased, except for rhinitis where the
      prevalence increased until six years of age, indicating no specific ordered
      sequence. CONCLUSIONS: Parentally reported possible asthma, eczema and food
      allergy had a curvilinear prevalence course across age with a maximum at age 3,
      while rhinitis prevalence increased consistently with age. Co-occurrence between
      possible asthma and atopic manifestations was common, and some combinations were
      more common than others, but there was no evidence of a specific ordered onset
      sequence.

PMID- 23953350
TI  - Lifetime direct medical costs of treating type 2 diabetes and diabetic
      complications.
AB  - BACKGROUND: Lifetime direct medical cost of treating type 2 diabetes and diabetic
      complications in the U.S. is unknown. PURPOSE: This study provides nationally
      representative estimates of lifetime direct medical costs of treating type 2
      diabetes and diabetic complications in people newly diagnosed with type 2
      diabetes, by gender and by age at diagnosis. METHODS: A type 2 diabetes
      simulation model was used to simulate the disease progression and direct medical
      costs among a cohort of newly diagnosed type 2 diabetes patients. The study
      sample used for the simulation was based on data from the 2009-2010 National
      Health and Nutritional Examination Survey. The costs of treating type 2 diabetes
      and diabetic complications were derived from published literature. Annual medical
      costs were accumulated over the life span of type 2 diabetes to determine the
      lifetime medical costs. All costs were calculated from a healthcare system
      perspective, and expressed in 2012 dollars. RESULTS: In men diagnosed with type 2
      diabetes at ages 25-44 years, 45-54 years, 55-64 years, and >= 65 years, the
      lifetime direct medical costs of treating type 2 diabetes and diabetic
      complications were $124,700, $106,200, $84,000, and $54,700, respectively. In
      women, the costs were $130,800, $110,400, $85,500, and $56,600, respectively. The
      age-gender weighted average of the lifetime medical costs was $85,200, of which
      53% was due to treating diabetic complications. The cost of managing
      macrovascular complications accounted for 57% of the total complication cost.
      CONCLUSIONS: Over the lifetime, type 2 diabetes imposes a substantial economic
      burden on healthcare systems. Effective interventions that prevent or delay type
      2 diabetes and diabetic complications might result in substantial long-term
      savings in healthcare costs.

PMID- 23953351
TI  - Physical activity and the incidence of obesity in young African-American women.
AB  - BACKGROUND: Obesity occurs more commonly among African-American women than among
      other racial/ethnic groups, and most weight gain occurs before middle age.
      PURPOSE: The study prospectively investigated the relationship of vigorous
      exercise and brisk walking to the incidence of obesity (BMI >= 30) among African
      American women aged <40 years. METHODS: During 1995-2009 in the Black Women's
      Health Study, the current authors followed 20,259 African-American women who were
      aged <40 years and not obese at baseline. BMI, exercise, and walking were
      assessed at baseline and on biennial follow-up questionnaires. Data for BMI were
      collected through 2009. Data for exercise and walking were collected through
      2007. Validation and reproducibility data indicated that reporting was more
      accurate for vigorous exercise than for brisk walking. Cox proportional hazards
      models estimated incidence rate ratios (IRRs) and 95% CIs of incident obesity for
      hours/week of vigorous exercise and walking relative to "little or no exercise"
      (<1 hour/week of vigorous exercise and <1 hour/week of brisk walking). The
      analyses were conducted in 2012. RESULTS: The incidence of obesity decreased with
      increasing vigorous exercise; the IRR was 0.77 (95% CI=0.69, 0.85) for >= 7
      hours/week relative to little or no exercise; the IRRs were reduced both among
      women with a healthy weight (BMI <25) at baseline and among women who were
      overweight (BMI 25-<30) at baseline. The IRRs for brisk walking for exercise and
      walking for transport were <1.0 for most levels of walking, but without clear
      trends of decreasing risk with increasing time spent walking. CONCLUSIONS: The
      results suggest that vigorous exercise may reduce the incidence of obesity among
      young African-American women. Results for brisk walking were inconclusive.

PMID- 23953352
TI  - Walkability and physical activity: findings from Curitiba, Brazil.
AB  - BACKGROUND: Evidence from developing countries is limited on how income level for
      a given neighborhood is related to physical activity among its residents.
      PURPOSE: The goal of the study was to examine the association between walkability
      and physical activity outcomes, and the effect of income on the relationship
      between walkability and physical activity in adults. METHODS: The Spaces for
      Physical Activity in Adults Study (ESPACOS Project) took place in Curitiba,
      Brazil. Data were collected in 2010 in 32 census tracts selected to vary in
      income and walkability, as measured by GIS. Participants were 697 individuals
      aged 18-65 years (52.0% were women) randomly sampled from the selected
      neighborhoods. The International Physical Activity Questionnaire was used to
      measure physical activity. All analyses were conducted in 2012. RESULTS: The
      proportion of those who walked for transportation for >= 150 minutes/week was
      21.1% in low-walkability areas, and ranged from 33.5% to 35.0% in high
      walkability areas. A total of 12.6% of residents were found to walk for leisure
      for >= 150 minutes/week; this result did not vary across quadrants of walkability
      and income level. The prevalence of leisure-time moderate-to-vigorous physical
      activity (MVPA) was 7.1-10.5 percentage points higher in high-compared to low
      walkability areas. After adjusting for all individual confounders, walkability
      showed an independent association with walking for transport (OR=2.10, 95%
      CI=1.31, 3.37, p=0.002) and leisure-time MVPA (OR=1.57, 95% CI=1.06, 2.32,
      p=0.024). Neighborhood income level was independently associated with leisure
      time MVPA (OR=1.70, 95% CI=1.06, 2.74, p=0.029). No association was found between
      walkability and walking for leisure. No interaction was found between walkability
      and neighborhood income level. CONCLUSIONS: This study, among adults living in
      Curitiba, Brazil, confirms findings from studies of high-income countries showing
      that walkability is positively associated with physical activity. People living
      in high-walkability areas were more likely to be physically active regardless of
      their neighborhood income level.

PMID- 23953353
TI  - Sitting-time, physical activity, and depressive symptoms in mid-aged women.
AB  - BACKGROUND: Associations of sitting-time and physical activity with depression
      are unclear. PURPOSE: To examine concurrent and prospective associations between
      both sitting-time and physical activity with prevalent depressive symptoms in mid
      aged Australian women. METHODS: Data were from 8950 women, aged 50-55 years in
      2001, who completed mail surveys in 2001, 2004, 2007, and 2010. Depressive
      symptoms were assessed using the Center for Epidemiological Studies Depression
      questionnaire. Associations between sitting-time (<= 4 hours/day, >4-7 hours/day,
      >7 hours/day) and physical activity (none, some, meeting guidelines) with
      depressive symptoms (symptoms/no symptoms) were examined in 2011 in concurrent
      and lagged mixed-effect logistic modeling. Both main effects and interaction
      models were developed. RESULTS: In main effects modeling, women who sat >7
      hours/day (OR=1.47, 95% CI=1.29, 1.67) and women who did no physical activity
      (OR=1.99, 95% CI=1.75, 2.27) were more likely to have depressive symptoms than
      women who sat <= 4 hours/day and who met physical activity guidelines,
      respectively. In interaction modeling, the likelihood of depressive symptoms in
      women who sat >7 hours/day and did no physical activity was triple that of women
      who sat <= 4 hours/day and met physical activity guidelines (OR 2.96, 95%
      CI=2.37, 3.69). In prospective main effects and interaction modeling, sitting
      time was not associated with depressive symptoms, but women who did no physical
      activity were more likely than those who met physical activity guidelines to have
      future depressive symptoms (OR=1.26, 95% CI=1.08, 1.47). CONCLUSIONS: Increasing
      physical activity to a level commensurate with guidelines can alleviate current
      depression symptoms and prevent future symptoms in mid-aged women. Reducing
      sitting-time may ameliorate current symptoms.

PMID- 23953354
TI  - Active travel to work and cardiovascular risk factors in the United Kingdom.
AB  - BACKGROUND: Increasing active travel (walking, cycling, public transport) is
      increasingly seen as integral to strategies to raise physical activity levels.
      PURPOSE: This study examined (1) sociodemographic correlates of active travel to
      work and (2) associations between active travel and cardiovascular risk factors
      in the United Kingdom (UK). METHODS: Data come from Understanding Society, a
      nationally representative survey of UK residents in 2009/2011, analyzed in 2012.
      Multinomial logistic regression assessed associations between sociodemographic
      factors and mode of transport to work. Linear and logistic regression was used to
      examine associations between mode of travel and overweight/obesity, and having
      hypertension or diabetes. RESULTS: A total of 69% of participants traveled to
      work using private transport, with public transport, walking, and cycling used by
      16%, 12%, and 3%, respectively. Use of any active travel was more likely in
      participants living in London. Black participants were more likely to walk
      (AOR=1.41, 95% CI=1.08, 1.84) or take public transport (AOR=2.34, 95% CI=1.88,
      2.90) to work than whites. Using public transport, walking, or cycling to work
      was associated with a lower likelihood of being overweight (AOR=0.80, 95%
      CI=0.54, 0.88 for walking). Walking or cycling was associated with a lower
      likelihood of having diabetes, and walking was associated with a lower likelihood
      of having hypertension than private transport (AOR=0.83, 95% CI=0.71, 0.97).
      CONCLUSIONS: There are wide variations in the mode of travel to work across
      regions and sociodemographic groups in the UK. The protective association between
      active travel and cardiovascular risk demonstrated in this nationally
      representative study adds to growing evidence that concerted policy focus in this
      area may benefit population health.

PMID- 23953355
TI  - Objective food environments and health outcomes.
AB  - BACKGROUND: Pathways by which food environments affect residents' diet-related
      outcomes are still unclear. Understanding pathways may help decision makers
      identify food environment strategies to promote healthy diets. PURPOSE: To
      examine the hypothesis that residents' perceptions mediate the relationship
      between objective food environment and residents' diet quality and weight status.
      METHODS: In the Waterloo Region, Ontario, objective food environment data were
      collected from 422 food stores and 912 restaurants using the Nutrition
      Environment Measure Survey in Stores and Restaurants, a shelf-space measure of
      fruits and vegetables, and the Retail Food Environment Index. Waterloo Region
      households (n=2223) completed a subjective food environment perception survey;
      household members (n=4102) self-reported weight, height, and waist circumference.
      A subsample (1170 individuals within 690 households) completed diet records. Food
      environment data were collected in 2010; respondent data were collected from 2009
      2010; and data were analyzed in 2012. A series of gender-specific models were
      conducted to test mediation, adjusting for household income, car ownership, age,
      and education level. RESULTS: Residents' perceptions did not mediate the
      relationship between objective measures and diet-related outcomes; instead,
      results revealed the direct effect of several objectively measured factors of the
      food environment (notably food access and relative food affordability) on
      outcomes. Perceptions generally were not associated with diet-related outcomes.
      CONCLUSIONS: These results reveal that in this setting, strategies aimed at
      improving residents' perceptions may be less effective than those acting directly
      on food environments to improve food access and relative food affordability.

PMID- 23953357
TI  - Access to preventive health care for cancer survivors.
AB  - BACKGROUND: Access to health care, particularly effective primary and secondary
      preventive care, is critical for cancer survivors, in order to minimize the
      adverse sequelae of cancer and its treatment. PURPOSE: The goal of the study was
      to evaluate the association between cancer survivorship and access to primary and
      preventive health care. METHODS: Cancer survivors (n=4960) and individuals
      without a cancer history (n=64,431) aged >= 18 years, from the 2008-2010 Medical
      Expenditure Panel Survey (MEPS), were evaluated. Multiple measures of access and
      preventive services use were compared. The association between cancer
      survivorship and access and preventive services was evaluated with multivariate
      logistic regression models, stratified by age group (18-64 years and >= 65
      years), controlling for the effects of age, gender, race/ethnicity, education,
      marital status, and comorbidities. Data were analyzed in 2013. RESULTS: Cancer
      survivors aged >= 65 years had equivalent or greater access and preventive
      services use than individuals without a cancer history, in adjusted analyses.
      However, among those aged 18-64 years with private health insurance, cancer
      survivors were more likely than other individuals to have a usual source of care
      and to use preventive services, whereas uninsured or publicly insured cancer
      survivors were generally less likely to have a usual source of care and to use
      preventive services than were uninsured or publicly insured adults without a
      cancer history. CONCLUSIONS: Although access and preventive care use in cancer
      survivors is generally equivalent or greater compared to that of other
      individuals, disparities for uninsured and publicly insured cancer survivors aged
      18-64 years suggest that improvements in survivor care are needed.

PMID- 23953358
TI  - The nutrition and enjoyable activity for teen girls study: a cluster randomized
      controlled trial.
AB  - BACKGROUND: Obesity prevention among youth of low SES is a public health priority
      given the higher prevalence of youth obesity in this population subgroup.
      PURPOSE: To evaluate the 24-month impact of a school-based obesity prevention
      program among adolescent girls living in low-income communities. DESIGN: The
      study was a school-based group RCT, the Nutrition and Enjoyable Activity for Teen
      Girls (NEAT Girls) intervention. SETTING/PARTICIPANTS: The study involved 12
      secondary schools located in low-income communities in New South Wales,
      Australia. Participants were 357 adolescent girls (aged 13.2 +/- 0.5 years).
      INTERVENTION: The 12-month multicomponent intervention was guided by social
      cognitive theory and involved strategies to promote physical activity, reduce
      sedentary behaviors, and improve dietary outcomes. MAIN OUTCOME MEASURES: The
      primary outcome was BMI, and secondary outcomes were BMI z-score; percentage body
      fat (bioelectrical impedance analysis); physical activity (accelerometers);
      dietary intake; and recreational screen-time (self-report). Data were collected
      in 2010-2012 and analyzed in 2012. RESULTS: After 24 months, there were no
      intervention effects on BMI (adjusted mean difference -0.33, 95% CI= -0.97, 0.28,
      p=0.353) and BMI z-score (-0.12, 95% CI= -0.27, 0.04, p=0.178). However, there
      was a group-by-time interaction for percentage body fat (-1.96%, 95% CI= -3.02, 
      0.89, p=0.006). Intervention effects for physical activity, screen time, and
      dietary intake were not significant. CONCLUSIONS: The NEAT Girls intervention did
      not result in effects on the primary outcome. Further study of youth who are "at
      risk" of obesity should focus on strategies to improve retention and adherence in
      prevention programs. TRIAL REGISTRATION: This study is registered at Australian
      New Zealand Clinical Trials ACTRN1261000033004.

PMID- 23953356
TI  - Evaluating a standardized measure of healthcare personnel influenza vaccination.
AB  - BACKGROUND: Methods of measuring influenza vaccination of healthcare personnel
      (HCP) vary substantially, as do the groups of HCP that are included in any given
      set of measurements. Thus, comparison of vaccination rates across healthcare
      facilities is difficult. PURPOSE: The goal of the study was to determine the
      feasibility of implementing a standardized measure for reporting HCP influenza
      vaccination data in various types of healthcare facilities. METHODS: A total of
      318 facilities recruited in four U.S. jurisdictions agreed to participate in the
      evaluation, including hospitals, long-term care facilities, dialysis clinics,
      ambulatory surgery centers, and physician practices. HCP in participating
      facilities were categorized as employees, credentialed non-employees, or other
      non-employees using standard definitions. Data were gathered using cross
      sectional web-based surveys completed at three intervals between October 2010 and
      May 2011; data were analyzed in February 2012. RESULTS: 234 facilities (74%)
      completed all three surveys. Most facilities could report on-site employee
      vaccination; almost one third could not provide complete data on HCP vaccinated
      outside the facility, contraindications, or declinations, primarily due to
      missing non-employee data. Inability to determine vaccination status of
      credentialed and other non-employees was cited as a major barrier to measure
      implementation by 24% and 27% of respondents, respectively. CONCLUSIONS: Using
      the measure to report employee vaccination status was feasible for most
      facilities; tracking non-employee HCP was more challenging. Based on evaluation
      findings, the measure was revised to limit the types of non-employees included.
      Although the revised measure is less comprehensive, it is more likely to produce
      valid vaccination coverage estimates. Use of this standardized measure can inform
      quality improvement efforts and facilitate comparison of HCP influenza
      vaccination among facilities.

PMID- 23953359
TI  - Prostate-specific antigen and prostate cancer mortality: a systematic review.
AB  - CONTEXT: Although findings from recently published clinical trials and a review
      from the U.S. Preventive Services Task Force suggest that there is limited to no
      prostate cancer mortality benefit associated with prostate-specific antigen (PSA)
      screening, confusion remains as to whether the use of PSA as a screening tool for
      prostate cancer is warranted. EVIDENCE ACQUISITION: A systematic literature
      review was done in 2012 to identify case-control studies from the past 20 years
      that focused on evaluating the association between screening for prostate cancer
      and prostate cancer mortality. Emphasis was put on synthesizing the results of
      these studies, evaluating their limitations, and identifying remaining questions
      and issues that should be addressed in future studies. EVIDENCE SYNTHESIS: A
      total of seven studies were identified in this time period, with the majority
      suggesting that a reduction in prostate cancer mortality is associated with PSA
      screening. However, the findings may be limited by various biases inherent to
      case-control studies of screening tests, such as selection biases resulting from
      both case and control subject selection, exposure measurement issues, lead and
      length biases, and issues specific to prostate cancer screening such as the
      influence of digital rectal examinations. CONCLUSIONS: Findings from existing
      case-control studies of PSA and prostate cancer mortality suggest that there is a
      mortality benefit from PSA screening. However, these studies may be limited by
      bias and must therefore be interpreted with caution. As uncertainty regarding PSA
      screening remains, future studies to evaluate the association between PSA and
      prostate cancer mortality should address these potential biases directly.

PMID- 23953360
TI  - Agricultural subsidies and the American obesity epidemic.
AB  - Government-issued agricultural subsidies are worsening obesity trends in America.
      Current agricultural policy remains largely uninformed by public health
      discourse. Although findings suggest that eliminating all subsidies would have a
      mild impact on the prevalence of obesity, a revision of commodity programs could
      have a measurable public health impact on a population scale, over time. Policy
      reforms will be important determinants of the future of obesity in America,
      primarily through indemnity program revisions, and the allocation of increasing
      amounts of resources to sustainable agriculture. Public health intervention will
      be required at the policy level to promote healthy behavioral changes in
      consumers. The 2013 Farm Bill will be the key mechanism to induce such policy
      change in the near future. 

PMID- 23953361
TI  - Analysis of legal and scientific issues in court challenges to graphic tobacco
      warnings.
AB  - Smoking is the leading preventable cause of death in the U.S., yet cigarette
      health warnings in the U.S. are among the weakest in the world. In 2011, the FDA
      issued regulations mandating that graphic warnings be displayed on every
      cigarette pack sold in the U.S. Almost immediately, the tobacco industry
      challenged the warnings on First Amendment grounds. In March 2013, the FDA
      withdrew the graphic warning mandate, choosing instead to pursue additional
      research and then issue requirements for a new set of warnings. These warnings
      almost certainly will be challenged by the tobacco industry. The current paper
      describes the legal standards that will be used to assess the warnings, and the
      empirical questions that must be answered in order to determine whether each
      standard has been met. The paper also identifies errors the FDA could make in
      choosing images to be evaluated that would cause the images to be unable to meet
      the standards, regardless of the scientific evidence the FDA can establish. To be
      on safest ground, the FDA should adopt images that depict factual health
      consequences of smoking and should avoid images that could be interpreted as
      opinions. The FDA will have a high likelihood of prevailing in legal challenges
      to the warnings if there is evidence demonstrating that graphic warnings are
      necessary to counter past industry deception or that graphic warnings affect
      smoking behavior better than textual warnings. Even without evidence of the
      impact of graphic warnings on behavior, strong evidence that they affect
      behavioral intent, and that intent predicts behavior, should be sufficient for
      the warnings to be upheld. Alternatively, evidence that graphic warnings lead to
      more accurate consumer assessment of smoking risks should also be sufficient. 

PMID- 23953362
TI  - Adverse health effects of nighttime lighting: comments on American Medical
      Association policy statement.
AB  - The American Medical Association House of Delegates in June of 2012 adopted a
      policy statement on nighttime lighting and human health. This major policy
      statement summarizes the scientific evidence that nighttime electric light can
      disrupt circadian rhythms in humans and documents the rapidly advancing
      understanding from basic science of how disruption of circadian rhythmicity
      affects aspects of physiology with direct links to human health, such as cell
      cycle regulation, DNA damage response, and metabolism. The human evidence is also
      accumulating, with the strongest epidemiologic support for a link of circadian
      disruption from light at night to breast cancer. There are practical implications
      of the basic and epidemiologic science in the form of advancing lighting
      technologies that better accommodate human circadian rhythmicity. 

PMID- 23953363
TI  - Commercial host (dram shop) liability: current status and trends.
AB  - Commercial host liability (CHL, also called dram shop liability) holds alcohol
      retailers liable for alcohol-attributable harm caused by serving alcohol,
      illegally, to a patron who is already intoxicated (adult liability) or underage
      (underage liability). The Community Preventive Services Task Force, based on a
      systematic research literature review, concluded that CHL is an effective
      strategy for reducing excessive alcohol consumption. The current article
      describes the key components of CHL, its grounding in American jurisprudence, its
      adoption in the 50 states, and changes since 1989, when a similar assessment of
      these policies was conducted. The current paper focuses on three legislatively
      enacted restrictions: (1) increased evidentiary requirements; (2) limitations on
      damage awards; and (3) limitations on who may be sued. Data were collected in
      2011 and analyzed in 2012 and 2013. There has been substantial erosion of CHL
      during the past 2 decades. Fewer states recognized CHL in 2011 than in 1989, and
      more statutory restrictions were imposed during the study period among states
      that did recognize CHL; states are more likely to recognize underage than adult
      liability; and six states recognized a Responsible Beverage Services Practices
      affirmative defense in both 1989 and 2011. Implications of these findings for
      public health practitioners are discussed. 

PMID- 23953365
TI  - Policies to restrict secondhand smoke exposure: American College of Preventive
      Medicine Position Statement.
AB  - Secondhand smoke (SHS) exposure poses serious health risks for all nonsmokers,
      especially children and pregnant women. SHS is estimated to contribute to heart
      attacks in nonsmokers and nearly 53,800 deaths in the U.S. annually. A literature
      review of English-language articles was performed using PubMed, organizational
      websites, and pertinent review articles. Over the past 25 years, smokefree
      policies have protected nearly half the U.S. population from the adverse health
      effects of SHS. Smokefree policies have been shown to improve health outcomes
      with no consequences to local businesses. As of April 2013, a total of 24 states
      and 561 municipalities and territories, including the District of Columbia, New
      York City, Puerto Rico, and the U.S. Virgin Islands, have established laws that
      require nonhospitality workplaces, restaurants, and bars to be 100% smokefree.
      Four other states-Florida, Indiana, Louisiana, and Nevada-have smokefree laws
      that cover restaurants but provide an exemption for stand-alone bars. At least 14
      states have no smokefree laws. This paper describes the benefits of policies that
      reduce SHS and concludes with recommendations for future directions. The American
      College of Preventive Medicine (ACPM) recommends expanded clean indoor air
      policies for workplaces, stand-alone bars, restaurants, and multi-use family
      housing such as apartment buildings. ACPM recommends clean air policies for all
      university campuses, secondary school campuses, primary schools, child care
      centers, and city landmarks to further shift social norms and protect the health
      of children, adolescents, and adults. ACPM recommends closing existing gaps in
      clean indoor air policies. 

PMID- 23953364
TI  - Children in the public benefit system at risk of maltreatment: identification via
      predictive modeling.
AB  - A growing body of research links child abuse and neglect to a range of negative
      short- and long-term health outcomes. Determining a child's risk of maltreatment
      at or shortly after birth provides an opportunity for the delivery of targeted
      prevention services. This study presents findings from a predictive risk model
      (PRM) developed to estimate the likelihood of substantiated maltreatment among
      children enrolled in New Zealand's public benefit system. The objective was to
      explore the potential use of administrative data for targeting prevention and
      early intervention services to children and families. A data set of integrated
      public benefit and child protection records for children born in New Zealand
      between January 1, 2003, and June 1, 2006, was used to develop a risk algorithm
      using stepwise probit modeling. Data were analyzed in 2012. The final model
      included 132 variables and produced an area under the receiver operating
      characteristic curve of 76%. Among children in the top decile of risk, 47.8% had
      been substantiated for maltreatment by age 5 years. Of all children substantiated
      for maltreatment by age 5 years, 83% had been enrolled in the public benefit
      system before age 2 years. This analysis demonstrates that PRMs can be used to
      generate risk scores for substantiated maltreatment. Although a PRM cannot
      replace more-comprehensive clinical assessments of abuse and neglect risk, this
      approach provides a simple and cost-effective method of targeting early
      prevention services. 

PMID- 23953366
TI  - Licensure challenges in preventive medicine: a public policy issue.

PMID- 23953367
TI  - Integrated health and human services information systems to enhance population
      based and person-centered service.

PMID- 23953370
TI  - The NHS: free and caring or a market commodity?

PMID- 23953369
TI  - Expression of CD4+ T cell cytokine genes in the colorectal mucosa of inflammatory
      colorectal polyps in miniature dachshunds.
AB  - Inflammatory colorectal polyps (ICRPs) in miniature dachshunds are recently
      recognized as a major cause of large bowel diarrhea in this dog breed in Japan.
      ICRPs are characterized by the formation of multiple small polyps and a space
      occupying large polyp in the colorectal area, and are thought to be a novel form
      of inflammatory bowel disease (IBD). In humans, specific cytokine patterns
      attributed to T helper (Th)1, Th17 and regulatory T cells have important roles in
      the pathogenesis of IBD. Thus, the aim of the present study was to assess the
      gene expression of cytokines of T cell subsets in the colorectal mucosa from dogs
      with ICRPs. Colorectal mucosal specimens from 10 dogs with ICRPs and 14 control
      dogs were used in this study. Interferon (IFN)-gamma, interleukin (IL)-4, IL-17A
      and IL-10 mRNA expression was assessed using quantitative real-time PCR. IL-17A
      mRNA expression was significantly increased in large polyps compared to small
      polyps and controls. IFN-gamma and IL-10 mRNA expression in large polyps were
      significantly higher than in controls. There was no significant difference in IL
      4 mRNA expression among the three groups. IL-17A is thought to play important
      roles in the pathogenesis of ICRPs. IL-10 up-regulation could oppose the
      proinflammatory function of IL-17A. 

PMID- 23953371
TI  - Cardiovascular health for all.

PMID- 23953372
TI  - Slimming down childhood obesity.

PMID- 23953373
TI  - Quality of care and patient safety in the UK: the way forward after Mid
      Staffordshire.

PMID- 23953374
TI  - Evidence-based treatments for STEMI: are we doing enough?

PMID- 23953375
TI  - Remote preconditioning and all-cause mortality.

PMID- 23953376
TI  - TRILOGY ACS: prasugrel of benefit only after angiography?

PMID- 23953377
TI  - Keith Fox: the pursuit of GRACE, RITA, and other affairs of the heart.

PMID- 23953378
TI  - Vitamin A supplementation in Indian children.

PMID- 23953379
TI  - Vitamin A supplementation in Indian children.

PMID- 23953380
TI  - Vitamin A supplementation in Indian children.

PMID- 23953381
TI  - Vitamin A supplementation in Indian children - Authors' reply.

PMID- 23953382
TI  - Vitamin A supplementation in Indian children.

PMID- 23953383
TI  - Vitamin A supplementation in Indian children.

PMID- 23953384
TI  - Cardioprotective and prognostic effects of remote ischaemic preconditioning in
      patients undergoing coronary artery bypass surgery: a single-centre randomised,
      double-blind, controlled trial.
AB  - BACKGROUND: Remote ischaemic preconditioning has been associated with reduced
      risk of myocardial injury after coronary artery bypass graft (CABG) surgery. We
      investigated the safety and efficacy of this procedure. METHODS: Eligible
      patients were those scheduled to undergo elective isolated first-time CABG
      surgery under cold crystalloid cardioplegia and cardiopulmonary bypass at the
      West-German Heart Centre, Essen, Germany, between April, 2008, and October, 2012.
      Patients were prospectively randomised to receive remote ischaemic
      preconditioning (three cycles of 5 min ischaemia and 5 min reperfusion in the
      left upper arm after induction of anaesthesia) or no ischaemic preconditioning
      (control). The primary endpoint was myocardial injury, as reflected by the
      geometric mean area under the curve (AUC) for perioperative concentrations of
      cardiac troponin I (cTnI) in serum in the first 72 h after CABG. Mortality was
      the main safety endpoint. Analysis was done in intention-to-treat and per
      protocol populations. This trial is registered with ClinicalTrials.gov, number
      NCT01406678. FINDINGS: 329 patients were enrolled. Baseline characteristics and
      perioperative data did not differ between groups. cTnI AUC was 266 ng/mL over 72
      h (95% CI 237-298) in the remote ischaemic preconditioning group and 321 ng/mL
      (287-360) in the control group. In the intention-to-treat population, the ratio
      of remote ischaemic preconditioning to control for cTnI AUC was 0.83 (95% CI 0.70
      0.97, p=0.022). cTnI release remained lower in the per-protocol analysis (0.79,
      0.66-0.94, p=0.001). All-cause mortality was assessed over 1.54 (SD 1.22) years
      and was lower with remote ischaemic preconditioning than without (ratio 0.27, 95%
      CI 0.08-0.98, p=0.046). INTERPRETATION: Remote ischaemic preconditioning provided
      perioperative myocardial protection and improved the prognosis of patients
      undergoing elective CABG surgery. FUNDING: German Research Foundation.

PMID- 23953385
TI  - Prasugrel versus clopidogrel for patients with unstable angina or non-ST-segment
      elevation myocardial infarction with or without angiography: a secondary,
      prespecified analysis of the TRILOGY ACS trial.
AB  - BACKGROUND: Treatment with prasugrel and aspirin improves outcomes compared with
      clopidogrel and aspirin for patients with acute coronary syndrome who have had
      angiography and percutaneous coronary intervention; however, no clear benefit has
      been shown for patients managed first with drugs only. We assessed outcomes from
      the TRILOGY ACS trial based on whether or not patients had coronary angiography
      before treatment was chosen. METHODS: TRILOGY ACS (ClinicalTrials.gov number
      NCT00699998) was a randomised controlled trial, done at more than 800 sites
      worldwide. Patients with non-ST-elevation acute coronary syndrome who were
      selected for management without [corrected] revascularisation were randomly
      assigned to clopidogrel or prasugrel.The primary endpoint was cardiovascular
      death, myocardial infarction, or stroke at 30 months. In the present analysis we
      assessed differences in the primary endpoint by angiography status and whether
      the effects of treatment on the primary endpoint differed between patients who
      had angiography before enrolment and those who had not. FINDINGS: 7243 patients
      younger than 75 years were included in the TRILOGY ACS primary analysis. 3085
      (43%) had angiography at baseline, 4158 (57%) had not. Fewer patients who had
      angiography reached the primary endpoint at 30 months compared with those who did
      not have angiography, according to Kaplan-Meier analysis (281/3085 [12.8%] vs
      480/4158 [16.5%], adjusted hazard ratio [HR] 0.63, 95% CI 0.53-0.75; p<0.0001).
      The proportion of patients who reached the primary endpoint was lower in the
      prasugrel group than in the clopidogrel group for those who had angiography
      (122/1524 [10.7%] vs 159/1561 [14.9%], HR 0.77, 95% CI 0.61-0.98; p=0.032) but
      did not differ between groups in patients who did not have angiography (242/2096
      [16.3%] vs 238/2062 [16.7%], HR 1.01, 0.84-1.20; p=0.94; pinteraction=0.08).
      Overall, TIMI major bleeding and GUSTO severe bleeding were rare. Bleeding
      outcomes tended to be higher with prasugrel but did not differ significantly
      between treatment groups in either angiography cohort. INTERPRETATION: Among
      patients who had angiography who took prasugrel there were fewer cardiovascular
      deaths, myocardial infarctions, or strokes than in those who took clopidogrel.
      This result needs to be corroborated, but it is consistent with previous trials
      of more versus less intensive antiplatelet treatment. When angiography is done
      for acute coronary syndrome and anatomic coronary disease confirmed, the benefits
      and risks of intensive antiplatelet treatment exist whether the patient is
      treated with drugs or percutaneous coronary intervention. FUNDING: Daiichi
      Sankyo, Eli Lilly.

PMID- 23953386
TI  - Reperfusion therapy for STEMI: is there still a role for thrombolysis in the era
      of primary percutaneous coronary intervention?
AB  - In the past ten years, primary percutaneous coronary intervention (PCI) has
      replaced thrombolysis as the revascularisation strategy for many patients
      presenting with ST-segment elevation myocardial infarction (STEMI). However,
      delivery of primary PCI within evidence-based timeframes is challenging, and
      health-care provision varies substantially worldwide. Consequently, even with the
      ideal circumstances of rapid initial diagnosis, long transfer delays to the
      catheter laboratory can occur. These delays are detrimental to outcomes for
      patients and can be exaggerated by variations in timing of patients' presentation
      and diagnosis. In this Series paper we summarise the value of immediate out-of
      hospital thrombolysis for STEMI, and reconsider the potential therapeutic
      interface with a contemporary service for primary PCI. We review recent trial
      data, and explore opportunities for optimisation of STEMI outcomes with a
      pharmacoinvasive approach. 

PMID- 23953387
TI  - What is the optimum adjunctive reperfusion strategy for primary percutaneous
      coronary intervention?
AB  - Acute ST-segment elevation myocardial infarction (STEMI) is a dynamic, thrombus
      driven event. As understanding of its pathophysiology has improved, the central
      role of platelets in initiation and orchestration of this process has become
      clear. Key components of STEMI include formation of occlusive thrombus, mediation
      and ultimately amplification of the local vascular inflammatory response
      resulting in increased vasoreactivity, oedema formation, and microvascular
      obstruction. Activation, degranulation, and aggregation of platelets are the
      platforms from which these components develop. Therefore, prompt, potent, and
      predictable antithrombotic therapy is needed to optimise clinical outcomes after
      primary percutaneous coronary intervention. We review present pharmacological and
      mechanical adjunctive therapies for reperfusion and ask what is the optimum
      combination when primary percutaneous coronary intervention is used as the mode
      of revascularisation in patients with STEMI. 

PMID- 23953388
TI  - Future treatment strategies in ST-segment elevation myocardial infarction.
AB  - Over the past five decades, management of acute ST-segment elevation myocardial
      infarction (STEMI) has evolved substantially. Current treatment encompasses a
      systematic chain of network activation, antithrombotic drugs, and rapid
      instigation of mechanical reperfusion, although pharmacoinvasive strategies
      remain relevant. Secondary prevention with drugs and lifestyle modifications
      completes the contemporary management package. Despite a tangible improvement in
      outcomes, STEMI remains a frequent cause of morbidity and mortality, justifying
      the quest to find new therapeutic avenues. Ways to reduce delays in doing
      coronary angioplasty after STEMI onset include early recognition of symptoms by
      patients and prehospital diagnosis by paramedics so that the emergency room can
      be bypassed in favour of direct admission to the catheterisation laboratory.
      Mechanical reperfusion can be optimised by improvements to stent design, whereas
      visualisation of infarct size has been improved by developments in cardiac MRI.
      Novel treatments to modulate the inflammatory component of atherosclerosis and
      the vulnerable plaque include use of bioresorbable vascular scaffolds and anti
      proliferative drugs. Translational efforts to improve patients' outcomes after
      STEMI in relation to cardioprotection, cardiac remodelling, and regeneration are
      also being realised. 

PMID- 23953389
TI  - A case of meningoencephalitis by the relapsing fever spirochaete Borrelia
      miyamotoi in Europe.

PMID- 23953391
TI  - Interactions of Plasmodium juxtanucleare and chicken anaemia virus: establishing
      a model.
AB  - The pathogens Plasmodium juxtanucleare and chicken anaemia virus (CAV) are easily
      transmitted and potentially harmful to chickens. In this study, we established an
      experimental model to investigate the effects of avian malaria caused by P.
      juxtanucleare in white leghorn specific-pathogen-free (SPF) chicks previously
      immunosuppressed with CAV. Parasitaemia, haematological variables and clinical
      and pathological parameters were determined in four different experimental
      groups: chicks coinfected by CAV and P. juxtanucleare strain (Coinfected group),
      chicks exclusively infected by CAV (CAV group) or P. juxtanucleare (Malaria
      group) and uninfected chicks (Control group). Our data demonstrated that P.
      juxtanucleare parasitaemia was significantly higher in the Coinfected group.
      Furthermore, haematological parameters, including the RBC, haematocrit and
      haemoglobin concentration were significantly reduced in coinfected chicks. In
      agreement with the changes observed in haematological features, the mortality
      among coinfected chicks was higher compared with animals with single infections.
      Clinical analysis indicated moderate changes related to different organs size
      (bursa of Fabricius, heart and liver) in coinfected birds. The experimental
      coinfection of SPF chickens with P. juxtanucleare and CAV may represent a
      research tool for the study of avian malaria after CAV immunosuppression,
      enabling measurement of the impacts caused by different pathogens during malarial
      infection.

PMID- 23953392
TI  - Patients respond similarly to paper and electronic versions of the WOMAC and SF
      12 following total joint arthroplasty.
AB  - The purpose of this study was to determine agreement between responses on
      electronic and paper versions of the WOMAC and SF-12(v2) questionnaires following
      total hip and total knee arthroplasty. Patients completed both electronic and
      paper questionnaires with a one week interval in-between. The order in which they
      completed the two versions was randomly assigned. A total of 53 patients
      completed the study, with a mean age of 69 years (range 50-90 years). The
      intraclass correlation coefficients (ICC) were high, indicating excellent
      agreement (WOMAC ICC = 0.96, 95% CI 0.94-0.98), SF-12 (PCS) ICC = 0.95, 95% CI
      0.92-0.97; SF-12 (MCS) ICC = 0.92, 95%CI 0.86-0.95). Online data collection may
      be substituted for the traditional paper method with no significant effect on the
      criterion validity of the questionnaires.

PMID- 23953393
TI  - Implant standardization for hemiarthroplasty: implementation of a pricing matrix
      system at a level II community based trauma system.
AB  - Our purpose was to perform a clinical and financial analysis of a pricing matrix
      system on operative hip fracture care concerning hemiarthroplasty for displaced
      femoral neck fractures in elderly low demand patients. Data analysis on 81 pre
      matrix and 88 post-matrix patients demonstrated no significant differences in
      age, sex, ASA or fracture pattern between the two groups. No difference in
      surgical approach, cement use, prosthesis choice, operative time, estimated blood
      loss, or intra-operative complication rate was observed. No radiographic
      difference in subsidence or loosening was demonstrated. Readmission form cardiac,
      UTI, PE or DVT rates were similar between groups and no increase in revision
      surgery or mortality was observed. Overall, our hospital realized a 37% reduction
      in implant costs, resulting in $165,500 savings for the calendar year. 

PMID- 23953394
TI  - Risk factors for total knee arthroplasty aseptic revision.
AB  - Using a Total Joint Replacement Registry, patient, operative, implant, surgeon,
      and hospital risk factors associated with aseptic revision after primary total
      knee arthroplasty (TKA) were evaluated. From 04/2001 to 12/31/2010 64,017 primary
      TKA cases, followed for a median time of 2.9 years, were registered and included
      in the analysis. Patients were predominantly female, white, with osteoarthritis,
      and obese. The crude aseptic revision rate is 1.3% (N=826). The cumulative
      survival for aseptic revision at 8 years is 97.6% (95% CI 97.3%-97.8%). Adjusted
      models revealed that age, race, body mass index, diabetic status, bilateral
      procedures, high-flex implants, and the LCS mobile bearing knee are associated
      with risk of revision. Gender, general health status, diagnosis, surgeon
      fellowship training, surgeon volume, hospital volume, fixation, and bearing
      surface material were not associated with risk of aseptic revision. Recognition
      of surgical factors associated with TKA failures can help the surgeons with their
      choices of surgical techniques and implants.

PMID- 23953395
TI  - National obesity trends in total knee arthroplasty.
AB  - Obesity has reached epidemic proportions and in the US, the age-adjusted obesity
      prevalence is 32% for men and 36% for women. The osteoarthritis risk is nearly
      four-fold for obese men and five-fold for obese women. The purpose of this study
      was to evaluate the US national obesity trends of TKA utilization. The Nationwide
      Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency
      for Healthcare Research and Quality (AHRQ) 2002-2009 datasets were merged to
      identify 753,268 TKAs. Over this period, obese patients represented 15% of all
      TKAs. Despite well documented concerns regarding perioperative complications
      associated with TKA in obese patients, TKA utilization doubled from 2002-2009.
      Additionally, 30% of obese patients had greater than 3 co-morbidities, compared
      to 7% in the non-obese group. With greater complication risks, the increasing TKA
      utilization in obese patients is concerning and warrants increased attention. 

PMID- 23953396
TI  - Amyloid imaging in clinical trials.
AB  - The possibility to map amyloid-beta, the Alzheimer's disease hallmark protein, in
      vivo opens the application for amyloid imaging in clinical trials with disease
      modifying agents. Monitoring change in amyloid burden, particularly when
      potential amyloid-lowering drugs are at play, requires accurate analytical
      methods. Studies to date have used suboptimal methods that do not account for
      heterogeneous changes in flow associated with disease progression and potentially
      with anti-amyloid drugs. In this commentary, we discuss practical and
      methodological issues regarding longitudinal amyloid imaging and propose several
      quantitative, yet feasible, alternatives for reliable assessment of changes over
      time in amyloid burden. 

PMID- 23953397
TI  - Phenotypic expression of a novel C282Y/R226G compound heterozygous state in HFE
      hemochromatosis: molecular dynamics and biochemical studies.
AB  - Most adults affected with hereditary hemochromatosis are homozygous for a single
      point mutation of HFE (p.Cys282Tyr). Apart from the compound heterozygous state
      for the p.Cys282Tyr mutant and the widespread p.His63Asp variant allele, other
      rare HFE mutations can be found in trans and may have clinical impact. In the
      present report we describe the structural and functional consequences of a new
      mutation, namely the p.Arg226Gly which was inherited in trans with the
      p.Cys282Tyr allele in a patient affected with a mild iron overload. Because the
      R226G substitution is located in the vicinity of the normal Cys225S-S282Cys
      disulfide bond we initially investigated the structure of the variant by
      molecular dynamics techniques in order to estimate the effect of the mutation on
      the global structure of HFE domain alpha3. We found that the solvation free
      energy, hydrophobicity and formation of salt bridges are slightly modified with
      the global secondary structure of the alpha3 domain being conserved. In a
      previous paper, we demonstrated that the Q283P substitution leads to the loss of
      the normal Cys225S-S282Cys disulfide bridge. Similar to the Q283P substitution,
      the R226G substitution does not substitute a residue directly involved in the
      formation of the disulfide bridge. However, unlike the p.Gln283Pro variant which
      destroyed the normal disulfide bridge, the R226G mutation does not affect the
      normal Cys225S-S282Cys bridge. Furthermore based on cell line studies we clearly
      show that the mutation does not prevent cell surface localization, beta2
      microglobulin association and binding to transferrin receptor 1. This new
      compound heterozygous phenotype is very close to those of the C282Y/H63D compound
      heterozygous patients who display the biochemical hemochromatosis phenotype but
      with lower body iron stores than C282Y homozygotes. Our results do not exclude
      unknown genetic and/or metabolic factors that may act synergistically to increase
      the ferritin level. 

PMID- 23953398
TI  - Identification of a novel UROS mutation in a Chinese patient affected by
      congenital erythropoietic porphyria.

PMID- 23953399
TI  - Tyrosine/tyrosinate fluorescence at 700 MPa: a pressure unfolding study of
      chicken ovomucoid at pH 12.
AB  - The utility of tyrosine/tyrosinate fluorescence for pressure-unfolding studies of
      Trp-lacking proteins has been explored for the first time, with chicken ovomucoid
      (OVM) as target. A newly developed fluorescence spectrometer working in the range
      0.1-700 MPa is employed for this purpose. At 25  degrees C at pH 12, all six Tyr
      residues give tyrosine emission at 306 nm, implying that all five Tyr residues
      are well buried at pH 12 in the folded OVM, except one giving "half-tyrosinate"
      emission at 325 nm. Upon increasing pressure, however, a distinct intermediate
      state, in which domains 1 and 2 are selectively unfolded, appears and increases
      up to 700 MPa. Extrapolated to 0.1 MPa, this intermediate lies 8.8+/-2.6 kJ mol(
      1) above the native state, characterized with a partial molar volume smaller by 
      28.9+/-7.4 ml mol(-1). At 5  degrees C at 700 MPa, even domain 3 gives a sign of
      cold denaturation.

PMID- 23953400
TI  - Protein dynamics by neutron scattering.
AB  - Neutron scattering techniques represent a powerful tool for characterizing both
      the structure and dynamical properties of bio-systems, for example, proteins and
      membranes interacting with their solvents. In this paper, Elastic Neutron
      Scattering (ENS) data collected at the Institut Laue-Langevin (Grenoble, France)
      on dry and D2O hydrated lysozyme by varying hydration level are presented, and
      compared with previously published data on the same protein system, also with the
      addition of bio-protectants. The data have been collected with three different
      spectrometers, i.e. IN13, IN10 and IN4. This set of ENS data gives direct access
      to the temperature behavior of both (i) the Mean Square Displacement (MSD) and
      (ii) the characteristic system relaxation time. As a result, an explicative
      hypothesis on the relationship between the so-called "protein dynamical
      transition" (PDT) and the "fragile-to-strong dynamical crossover" (FSC) is
      formulated. Furthermore, by taking into proper account the effect of the finite
      instrumental energy resolution of the used spectrometers, the vibrational MSD of
      dry and hydrated lysozyme is calculated. The vibrational MSD of the lysozyme in
      the dry state resulted to be higher than the one in the hydrated state; the
      latter reaches the former at a temperature value of T=220K that corresponds to
      the temperature at which the FSC occurs. As a result, a cage effect resulting
      from the hydration water on the protein surface is hypothesized and subsequently
      linked to the FSC. 

PMID- 23953401
TI  - Advanced mucosal neoplasia of the anorectal junction: endoscopic resection
      technique and outcomes (with videos).
AB  - BACKGROUND: EMR at the anorectal junction (ARJ) is technically challenging.
      Issues of safety and procedural efficacy dictate that surgery is still performed
      as the primary management for noninvasive lesions in most centers. Modifications
      to the standard EMR technique may help to address the unique features and achieve
      safe and curative resection of most lesions. OBJECTIVE: To describe an effective
      and safe, modified EMR technique to remove advanced mucosal neoplasia (AMN) of
      the ARJ. DESIGN: Prospective, observational cohort study. SETTING: Academic,
      tertiary care referral center. PATIENTS: Patients undergoing EMR for AMN at the
      ARJ over 4.5 years, from June 2008 to December 2012. INTERVENTIONS: Use of long
      acting local anesthetic in the submucosal injectate, endoscopic resection over
      the dentate line and hemorrhoidal columns, prophylactic antibiotics for resection
      of lesions at high risk for bacteremia, and cap and gastroscope-assisted
      resection. MAIN OUTCOME MEASUREMENTS: Procedural success and safety. RESULTS:
      Twenty-six patients with lesions involving the ARJ were referred for EMR (males
      53.8%, median age 63, median lesion size 40 mm). Two patients went directly to
      surgery because of an endoscopic diagnosis of adenocarcinoma. EMR was performed
      in 24 lesions with complete adenoma clearance achieved in 100%. Four patients
      were admitted to the hospital. Focal adenoma recurrence was seen in 4 of 18
      patients (22%) at first surveillance colonoscopy and was managed by snare
      diathermy resection. No recurrences were found at the second follow-up
      colonoscopy. Procedural success, adenoma recurrence, and admission rates were
      similar between EMRs performed at the ARJ and proximal rectum on univariate
      analysis (all P > .05). LIMITATIONS: Single tertiary center, nonrandomized study.
      CONCLUSIONS: Simple modifications to the EMR technique allow safe and effective
      treatment of AMN at the ARJ on an outpatient basis and should be the first-line
      management when the risk of invasive disease is low.

PMID- 23953403
TI  - Rectal cancer developing in the setting of a cavernous hemangioma of the
      rectosigmoid colon.

PMID- 23953402
TI  - Acetic acid compared with i-scan imaging for detecting Barrett's esophagus: a
      randomized, comparative trial.
AB  - BACKGROUND: Traditional surveillance in patients with Barrett's esophagus (BE)
      has relied on random biopsies. Targeted biopsies that use advanced imaging
      modalities may significantly improve detection of specialized columnar epithelium
      (SCE). OBJECTIVE: We compared the efficacy of targeted biopsies that used i-scan
      or acetic acid to random biopsies in the detection of SCE. DESIGN: Patients with
      visible columnar lined epithelium or known BE were randomized at a 1:1 ratio to
      undergo acetic acid application or i-scan with targeted biopsies. SETTING:
      Targeted biopsies were performed based on surface architecture according to the
      Guelrud classification followed by 4-quadrant biopsies. PATIENTS: A total of 95
      patients were randomized. INTERVENTION: A total of 46 patients underwent acetic
      acid staining, and 49 underwent i-scan imaging. Random biopsies were performed in
      86 patients. MAIN OUTCOME MEASUREMENTS: The primary outcome was the yield of SCE
      as confirmed by histologic assessment. RESULTS: The diagnostic yield for SCE was
      significantly higher with targeted biopsies than with random biopsies in both
      groups combined (63% vs 24%; P = .0001). The yield of targeted biopsies was
      significantly greater with both i-scan (66% vs 21%; P = .009) and acetic acid
      (57% vs 26%; P = .012) technologies and did not differ between these groups. The
      accuracy for predicting SCE was 96% (k = .92) for i-scan and 86% (k = .70) for
      acetic acid analysis. LIMITATIONS: No dysplastic lesions were found. CONCLUSION:
      The i-scan or acetic acid-guided biopsies have a significantly higher diagnostic
      yield for identifying SCE, with significantly fewer biopsies, as compared with a
      protocol of random biopsies. Acetic acid and i-scan showed comparable results
      diagnosing SCE in our study. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01442506.).

PMID- 23953404
TI  - Assessment of rural soundscapes with high-speed train noise.
AB  - In the present study, rural soundscapes with high-speed train noise were assessed
      through laboratory experiments. A total of ten sites with varying landscape
      metrics were chosen for audio-visual recording. The acoustical characteristics of
      the high-speed train noise were analyzed using various noise level indices.
      Landscape metrics such as the percentage of natural features (NF) and Shannon's
      diversity index (SHDI) were adopted to evaluate the landscape features of the ten
      sites. Laboratory experiments were then performed with 20 well-trained listeners
      to investigate the perception of high-speed train noise in rural areas. The
      experiments consisted of three parts: 1) visual-only condition, 2) audio-only
      condition, and 3) combined audio-visual condition. The results showed that
      subjects' preference for visual images was significantly related to NF, the
      number of land types, and the A-weighted equivalent sound pressure level (LAeq).
      In addition, the visual images significantly influenced the noise annoyance, and
      LAeq and NF were the dominant factors affecting the annoyance from high-speed
      train noise in the combined audio-visual condition. In addition, Zwicker's
      loudness (N) was highly correlated with the annoyance from high-speed train noise
      in both the audio-only and audio-visual conditions. 

PMID- 23953405
TI  - 21st century climate change in the European Alps--a review.
AB  - Reliable estimates of future climate change in the Alps are relevant for large
      parts of the European society. At the same time, the complex Alpine region poses
      considerable challenges to climate models, which translate to uncertainties in
      the climate projections. Against this background, the present study reviews the
      state-of-knowledge about 21st century climate change in the Alps based on
      existing literature and additional analyses. In particular, it explicitly
      considers the reliability and uncertainty of climate projections. Results show
      that besides Alpine temperatures, also precipitation, global radiation, relative
      humidity, and closely related impacts like floods, droughts, snow cover, and
      natural hazards will be affected by global warming. Under the A1B emission
      scenario, about 0.25  degrees C warming per decade until the mid of the 21st
      century and accelerated 0.36  degrees C warming per decade in the second half of
      the century is expected. Warming will probably be associated with changes in the
      seasonality of precipitation, global radiation, and relative humidity, and more
      intense precipitation extremes and flooding potential in the colder part of the
      year. The conditions of currently record breaking warm or hot winter or summer
      seasons, respectively, may become normal at the end of the 21st century, and
      there is indication for droughts to become more severe in the future. Snow cover
      is expected to drastically decrease below 1500-2000 m and natural hazards related
      to glacier and permafrost retreat are expected to become more frequent. Such
      changes in climatic parameters and related quantities will have considerable
      impact on ecosystems and society and will challenge their adaptive capabilities.

PMID- 23953406
TI  - Effect of amputation level on the stress transferred to the femur by an
      artificial limb directly attached to the bone.
AB  - Attachment of an artificial limb directly to the skeleton has a number of
      potential benefits and the technique has been implemented for several amputation
      sites. In this paper the transfer of stress from an external, transfemoral
      prosthesis to the femur during normal walking activity is investigated. The
      stress distribution in the femur and at the implant-bone interface is calculated
      using finite element analysis for the 3D geometry and inhomogeneous, anisotropic
      material properties obtained from a CT scan of a healthy femur. Attachment of the
      prosthetic leg at three different levels of amputation is considered. Stress
      concentrations are found at the distal end of the bone and adjacent to the
      implant tip and stress shielding is observed adjacent to the implant. It is found
      that the stress distribution in the femur distal to the epiphysis, where the
      femur geometry is close to cylindrical, can be predicted from a cylindrical
      finite element model, using the correct choice of bone diameter as measured from
      a radiograph. Proximal to the lesser trochanter the stress decreases as the femur
      geometry diverges significantly from a cylinder. The stress concentration at the
      distal, resected end of the bone is removed when a collared implant is employed.
      These findings form the basis for appropriate settings of an external fail-safe
      device to protect the bone from excessive stress in the event of an undue load. 

PMID- 23953407
TI  - Analysis of FET-PET imaging for target volume definition in patients with gliomas
      treated with conformal radiotherapy.
AB  - BACKGROUND AND PURPOSE: Modern radiotherapy (RT) techniques such as stereotactic
      RT, intensity-modulated RT, or particle irradiation allow local dose escalation
      with simultaneous sparing of critical organs. Several trials are currently
      investigating their benefit in glioma reirradiation and boost irradiation. Target
      volume definition is of critical importance especially when steep dose gradient
      techniques are employed. In this manuscript we investigate the impact of O-(2-(F
      18)fluoroethyl)-l-tyrosine-positron emission tomography/computer tomography (FET
      PET/CT) on target volume definition in low and high grade glioma patients
      undergoing either first or re-irradiation with particles. METHODS AND MATERIAL:
      We investigated volumetric size and uniformity of magnetic resonance imaging
      (MRI)- vs. FET-PET/CT-derived gross tumor volumes (GTVs) and planning target
      volumes (PTVs) of 41 glioma patients. Clinical cases are presented to demonstrate
      potential benefits of integrating FET-PET/CT-planning into daily routine.
      RESULTS: Integrating FET-uptake into the delineation of GTVs yields larger
      volumes. Combined modality-derived PTVs are significantly enlarged in high grade
      glioma patients and in case of primary RT. The congruence of MRI and FET signals
      for the identification of glioma GTVs is poor with mean uniformity indices of
      0.39. MRI-based PTVs miss 17% of FET-PET/CT-based GTVs. Non significant
      alterations were detected in low grade glioma patients and in those undergoing
      reirradiation. CONCLUSIONS: Target volume definition for malignant gliomas during
      initial RT may yield significantly differing results depending upon the imaging
      modality, which the contouring process is based upon. The integration of both MRI
      and FET-PET/CT may help to improve GTV coverage by avoiding larger incongruences
      between physical and biological imaging techniques. In low grade gliomas and in
      cases of reirradiation, more studies are needed in order to investigate a
      potential benefit of FET-PET/CT for planning of RT.

PMID- 23953408
TI  - Normal tissue complication probability (NTCP) parameters for breast fibrosis:
      pooled results from two randomised trials.
AB  - INTRODUCTION: The dose-volume effect of radiation therapy on breast tissue is
      poorly understood. We estimate NTCP parameters for breast fibrosis after external
      beam radiotherapy. MATERIALS AND METHODS: We pooled individual patient data of
      5856 patients from 2 trials including whole breast irradiation followed with or
      without a boost. A two-compartment dose volume histogram model was used with
      boost volume as the first compartment and the remaining breast volume as second
      compartment. Results from START-pilot trial (n=1410) were used to test the
      predicted models. RESULTS: 26.8% patients in the Cambridge trial (5 years) and
      20.7% patients in the EORTC trial (10 years) developed moderate-severe breast
      fibrosis. The best fit NTCP parameters were BEUD3(50)=136.4 Gy, gamma50=0.9 and
      n=0.011 for the Niemierko model and BEUD3(50)=132 Gy, m=0.35 and n=0.012 for the
      Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot
      trial agreed well with the predicted rates. CONCLUSIONS: This large multi-centre
      pooled study suggests that the effect of volume parameter is small and the
      maximum RT dose is the most important parameter to influence breast fibrosis. A
      small value of volume parameter 'n' does not fit with the hypothesis that breast
      tissue is a parallel organ. However, this may reflect limitations in our current
      scoring system of fibrosis.

PMID- 23953409
TI  - Radiosensitivity and effect of hypoxia in HPV positive head and neck cancer
      cells.
AB  - BACKGROUND AND PURPOSE: HPV associated Head and Neck Squamous Cell Carcinoma
      (HNSCC) represents a distinct subgroup of HNSCC characterized by a favorable
      prognosis and a distinct molecular biology. Previous data from the randomized
      DAHANCA 5 trial indicated that HPV positive tumors did not benefit from hypoxic
      modifications by Nimorazole during radiotherapy, whereas a significant benefit
      was observed in the HPV negative tumors. However, more studies have demonstrated
      equal frequencies of hypoxic tumors among HPV-positive and HPV-negative tumors.
      The aim of the present study was to determine radiosensitivity, the impact of
      hypoxia and the effect of Nimorazole in HPV positive and HPV negative cell lines.
      MATERIALS AND METHOD: The used cell lines were: UDSCC2, UMSCC47 and UPCISCC90
      (HPV positive) and FaDuDD, UTSCC33 and UTSCC5 (HPV negative). Cells were cultured
      under normoxic or hypoxic conditions, and gene expression levels of previously
      established hypoxia induced genes were assessed by qPCR. Cells were irradiated
      with various doses under normoxia, hypoxia or hypoxia +1mM Nimorazole, and the
      clonogenic survival was determined. RESULTS: The HPV positive and HPV negative
      cell lines exhibited similar patterns of upregulation of hypoxia induced genes in
      response to hypoxia. The HPV positive cell lines were up to 2.4 times more
      radiation sensitive than HPV negative cell lines. However, all HPV positive cells
      displayed the same response to hypoxia in radiosensitivity, with an OER in the
      range 2.3-2.9, and a sensitizer effect of Nimorazole of 1.13-1.29, similar to HPV
      negative cells. CONCLUSIONS: Although HPV positive cells had a markedly higher
      radiosensitivity compared to HPV negative cells, they displayed the same relative
      radioresistance under hypoxia and the same relative sensitizer effect of
      Nimorazole. The clinical observation that HPV positive patients do not seem to
      benefit from Nimorazole treatment is not due to inherent differences in hypoxia
      sensitivity or response to Nimorazole, but can be accounted for by the overall
      higher radiosensitivity of HPV positive cells.

PMID- 23953410
TI  - Reduction of the dose to the elective neck in head and neck squamous cell
      carcinoma, a randomized clinical trial using intensity modulated radiotherapy
      (IMRT). Dosimetrical analysis and effect on acute toxicity.
AB  - BACKGROUND AND PURPOSE: A randomized trial was initiated to investigate whether a
      reduction of the dose to the elective nodal sites and the swallowing apparatus
      delivered by IMRT would result in a reduction of acute and late side effects
      without compromising tumor control. The aim of this paper is to report on
      dosimetrical analysis and acute toxicity. MATERIALS & METHODS: Two-hundred
      patients were randomized. In the standard arm, elective nodal volumes (PTVelect)
      were irradiated up to an equivalent dose of 50Gy. In the experimental arm an
      equivalent dose of 40Gy was prescribed to the PTVelect. The dose to the
      swallowing apparatus was kept as low as possible without compromising therapeutic
      PTV (PTVther) coverage. RESULTS: No significant difference was seen between both
      arms concerning PTVther coverage. The median D95 of the PTVelect was
      significantly lower in the experimental arm (39.5 vs 49.8Gy; p<0.001). Concerning
      the organs at risk, the dose to swallowing structures and spinal cord was
      significantly reduced. There was no significant difference in acute toxicity.
      Three months after radiotherapy there was significantly less grade ?3 dysphagia
      in the experimental arm (2% vs 11%; p=0.03). With a median follow-up of 6months
      no significant differences were observed in locoregional control, disease free
      survival or overall survival. CONCLUSIONS: Using IMRT we were able to
      significantly reduce the dose to the PTVelect and several organs at risk without
      compromising PTVther coverage. This resulted in a significant reduction of severe
      dysphagia 3months after radiotherapy. Further follow-up is necessary to
      investigate whether these observations translate into a benefit on late treatment
      related dysphagia without affecting treatment outcome.

PMID- 23953411
TI  - Fatigue during chemoradiotherapy for nasopharyngeal cancer and its relationship
      to radiation dose distribution in the brain.
AB  - BACKGROUND AND PURPOSE: Fatigue during head and neck radiotherapy may be related
      to radiation dose to the central nervous system (CNS). The impact of patient,
      tumour, and dosimetric variables on acute fatigue was assessed in nasopharyngeal
      cancer patients undergoing chemoradiotherapy. MATERIAL AND METHODS: Radiation
      dose to the following retrospectively-delineated CNS structures; brainstem,
      cerebellum, pituitary gland, pineal gland, hypothalamus, hippocampus and basal
      ganglia (BG) and clinical variables were related to incidence of ? grade 2
      fatigue in 40 patients. RESULTS: Sixty per cent of patients reported fatigue
      during and following radiotherapy. Dmean and D2 to the BG and Dmean to the
      pituitary gland were significantly associated with fatigue during radiation
      (P<0.01). Dmean to the cerebellum was associated with fatigue following
      radiotherapy and at any time (P < 0.01). After adjusting for clinical factors, an
      association remained between fatigue during radiotherapy and mean dose and D2 to
      the pituitary gland and BG (P = 0.012, 0.036, 0.009 and 0.018) and mean dose to
      the cerebellum following radiation and at any time (P = 0.042 and 0.029).
      CONCLUSION: Disruption of connections between BG, cerebellum, and higher cortical
      centres or disruption of pituitary-regulated hormonal balance may be implicated
      in the pathophysiology of radiation-related fatigue.

PMID- 23953412
TI  - Sorafenib sensitizes head and neck squamous cell carcinoma cells to ionizing
      radiation.
AB  - BACKGROUND AND PURPOSE: There is a great need to improve the outcome of
      locoregionally advanced squamous cell carcinomas of the head and neck (HNSCC).
      Standard treatment includes a combination of surgery, radio- and chemotherapy.
      The addition of molecular targeting agents to conventional treatment may improve
      outcomes. In this study the Raf inhibitor sorafenib was used to increase the
      radiosensitivity of HNSCC cell lines. MATERIAL AND METHODS: In a panel of six
      cell lines (A549, FaDu, UTSCC 60A, UTSCC 42A, UTSCC 42B, UTSCC 29)
      radiosensitivity was measured by colony formation assay and apoptosis and cell
      cycle analysis were performed by flow cytometry. DNA repair was analyzed by 53BP1
      immunohistochemistry. RESULTS: Sorafenib added prior to irradiation resulted in
      an increased cellular radiosensitivity (DEF0.5=1.11-1.84). Radiosensitization was
      not caused by an enhanced rate of apoptosis or cell cycle effects. In contrast,
      sorafenib was shown for the first time to block the repair of DNA double-strand
      breaks (DSB). CONCLUSION: Our data suggest that sorafenib may be used to overcome
      the radioresistance of HNSCC through the inhibition of DSB repair.

PMID- 23953413
TI  - High-risk CT features for detection of local recurrence after stereotactic
      ablative radiotherapy for lung cancer.
AB  - BACKGROUND AND PURPOSE: Early detection of local recurrences following
      stereotactic ablative radiotherapy (SABR) for lung cancer may allow for curative
      salvage treatment, but recurrence can be difficult to distinguish from fibrosis.
      We studied the clinical performance of CT imaging high-risk features (HRFs) for
      detecting local recurrence. MATERIALS AND METHODS: Patients treated with SABR for
      early stage lung cancer between 2003 and 2012 who developed pathology-proven
      local recurrence (n=12) were matched 1:2 to patients without recurrences (n=24),
      based on baseline factors. Serial CT images were assessed by blinded radiation
      oncologists. Previously reported HRFs were (1) enlarging opacity at primary site;
      (2) sequential enlarging opacity; (3) enlarging opacity after 12-months; (4)
      bulging margin; (5) loss of linear margin and (6) air bronchogram loss. RESULTS:
      All HRFs were significantly associated with local recurrence (p<0.01), and one
      new HRF was identified: cranio-caudal growth (p<0.001). The best individual
      predictor of local recurrence was opacity enlargement after 12-months (100%
      sensitivity, 83% specificity, p<0.001). The odds of recurrence increased 4-fold
      for each additional HRF detected. The presence of >=3 HRFs was highly sensitive
      and specific for recurrence (both >90%). CONCLUSION: The systematic assessment of
      post-SABR CT images for HRFs enables the accurate prediction of local recurrence.

PMID- 23953414
TI  - Accreditation of advanced imaging facilities for dentistry - assuring minimal
      standards for high quality diagnostic imaging.

PMID- 23953415
TI  - Bisphosphonate related osteonecrosis of the jaws: spontaneous or dental origin?
AB  - OBJECTIVE(S): Bisphosphonates are frequently used worldwide mostly in
      osteoporosis and skeletal bone metastases. However, a serious side-effect is
      bisphosphonate related osteonecrosis of the jaws (BRONJ). The mechanism behind
      BRONJ remains unclear. In literature several origins are suggested. Presence of
      the teeth in the jaws may play an important role. Therefore in this study 45
      patients were analyzed retrospectively. STUDY DESIGN: Files of 45 patients with a
      diagnosis of BRONJ were analyzed, meaning clinical features, bisphosphonate use,
      dental history including luxating moment and (previous) treatment. RESULTS: In
      97.5% (n = 44) a certain or presumable dental focus, such as extractions, a
      previous dental treatment or prosthesis complaints were found as initiating
      factor of BRONJ. CONCLUSION: In contrast to findings in literature, in our group
      of patients a dental focus was found in 44 of 45 cases. This implies a
      dentoalveolar start of BRONJ with subsequent spreading into the jaws in nearly
      all cases.

PMID- 23953416
TI  - A pilot-study of a minimally invasive technique to elevate the sinus floor
      membrane and place graft for augmentation using high hydraulic pressure: 18-month
      follow-up of 20 cases.
AB  - OBJECTIVE: To evaluate medical efficacy and safety of crestal, minimally invasive
      sinus floor augmentation (MISFA) using an innovative method based on high
      hydraulic pressure. STUDY DESIGN: Twenty MISFA using the novel Jeder-System were
      performed in 18 patients at 2 study sites in Vienna, Austria. The Jeder-System
      consists of the Jeder-drill, the Jeder-pump, and a connecting tube-set. The pump
      generates high hydraulic pressure (1.5 bar) pushing back the sinus membrane from
      the drill at the first perforation. The pump also monitors the whole procedure by
      constantly measuring pressure and volume. RESULTS: Five percent membrane
      perforation rate (1/20) only detected in the postoperative computed tomography
      scan and without implication for implant placement. Height gain of 9.2 +/- 1.7 mm
      achieved (from 4.6 +/- 1.4 mm to 13.8 +/- 2.3 mm). Average patient satisfaction
      was 9.82 on scale from 1 to 10 (10 = very satisfied). Mean duration of sick leave
      was 0.19 days. 18-month survival rate was 95% (1/20 implant lost). CONCLUSIONS:
      Within the limits of a prospective open cohort study with 20 cases, our data
      demonstrate the safety and medical efficacy of the novel method.

PMID- 23953417
TI  - The effect of glycemic control on Candida colonization of the tongue and the
      subgingival plaque in patients with type II diabetes and periodontitis.
AB  - OBJECTIVES: Identify the relationship between the tongue and subgingival plaque
      Candida colonization, and its relationship to the quality of glycemic control
      (assessed by glycosylated hemoglobin) and other confounders, in type II diabetics
      who have periodontitis. STUDY DESIGN: Candida species were isolated from the
      tongue and subgingival plaque of the 2 deepest periodontal pockets from 78
      patients, and were identified by RapID Yeast Plus System. Student's t test,
      chi(2) test or Fisher's exact test, analysis of variance, multivariate logistic
      regression analysis, and Spearman's correlation test were used. RESULTS: Candida
      species colonized 46 (59%) and 38 (48.7%) of the patients tongue and subgingival
      plaque, respectively. Subgingival Candida was more prevalent in females than
      males (P = .041). The quality of glycemic control correlated with the prevalence
      of subgingival Candida (P = .047) and the severity of gingival disease (P =
      .047). CONCLUSION: Poor glycemic control and female gender may be associated with
      increased subgingival Candida in patients with type II diabetes.

PMID- 23953418
TI  - Activation of the Akt/mTOR pathway in dentigerous cysts, odontogenic keratocysts,
      and ameloblastomas.
AB  - OBJECTIVE: The aim of this study was to investigate the Akt/mTOR pathway in
      dentigerous cysts (DCs), odontogenic keratocysts (OKCs), and ameloblastomas.
      STUDY DESIGN: A total of 90 cases were studied (30 DCs, 30 OKCs, and 30
      ameloblastomas). Patient records on age, sex, lesion location, symptoms, and
      radiographic and histopathologic features were collected. The phosphorylation of
      components of the Akt/mTOR pathway [p-Akt (Ser473), p-Akt (Thr308), and
      phosphorylated-ribosomal protein S6 (p-RPS6)] was studied using
      immunohistochemistry. Correlations with clinical features were analyzed using the
      Spearman rank test. RESULTS: Over 90% of OKCs and ameloblastomas and 60% of DCs
      stained positive for p-Akt (Ser473). Phospho-Akt (Thr308) was positive in 73% of
      ameloblastomas, 40% of OKCs, and 20% of DCs. Phospho-RPS6 was detected most
      frequently in OKCs (83%), followed by ameloblastomas (76%) and DCs (53%). No
      correlations were noted between the immunohistochemical findings and the
      clinicopathologic parameters. CONCLUSIONS: The Akt/mTOR pathway is upregulated in
      DCs, OKCs, and ameloblastomas. This pathway may be involved in the development of
      these lesions.

PMID- 23953419
TI  - Oral follicular lymphomas. A short report of 8 cases with assessment of the
      IGH/BCL2 gene fusion with fluorescence in situ hybridization.
AB  - OBJECTIVE: To present the clinicopathologic features and confirm the presence of
      the IGH/BCL2 gene fusion in an oral follicular lymphoma (OFL) series. STUDY
      DESIGN: Cases of OFLs were retrieved from a data base of non-Hodgkin lymphomas
      (NHL). Fluorescence in situ hybridization (FISH) was performed to confirm the
      IGH/BCL2 fusion. RESULTS: Eight (8.7%) of 92 NHL were OFLs. Six (75%) patients
      were male and two female (mean age: 73.4 +/- 14.8). The most frequent site was
      the palate. Five of the 8 patients are alive and without disease. Five (three
      grade 1 and two grade 2) of six successfully hybridized cases revealed the
      IGH/BCL2 gene fusion. The sixth case, a grade 3 follicular lymphoma (FL),
      demonstrated multiple BCL2 signals without IGH/BCL2 fusion. CONCLUSIONS: OFLs
      exhibit an indolent clinical behavior. In the present study, 5/6 cases in which
      FISH was successful had an IGH/BCL2 fusion as would result from the t(14;
      18)(q32; q21) translocation commonly seen in FL of extraoral sites.

PMID- 23953420
TI  - Molecular pathogenesis of keratocystic odontogenic tumors developing in nevoid
      basal cell carcinoma syndrome.
AB  - OBJECTIVE: The aim of this study was to investigate the molecular pathogenesis of
      keratocystic odontogenic tumors (KCOTs) that developed in nevoid basal cell
      carcinoma syndrome (NBCCS) patients. STUDY DESIGN: We analyzed germline and
      somatic mutations of the PTCH1 and its related genes, SMO and SUFU in 10 KCOTs
      that developed in 8 unrelated NBCCS patients. Methylation status of the PTCH1
      promoter was also investigated by bisulfite sequencing. RESULTS: Somatic
      mutations of PTCH1 were detected in 3 KCOTs. Two out of 3 somatic mutations were
      either identified as a polymorphism or located on the same allele as the germline
      mutation. Neither abnormal methylation of the PTCH1 promoter, loss of PTCH1, nor
      somatic mutation of SMO or SUFU was detected in any of the samples. CONCLUSIONS:
      Our results suggest that the tumorigenesis of most KCOTs associated with NBCCS
      cannot be explained by the classical 2-hit theory.

PMID- 23953421
TI  - Intramuscular changes of soft and hard areas after low-level static contraction
      of the masseter muscle and the correlations with muscle hardness and increase in
      water content: evaluations with sonographic elastography and magnetic resonance
      imaging.
AB  - OBJECTIVES: To investigate the intramuscular changes on sonographic elastography
      (SE) after low-level static contraction of the masseter muscle, and to clarify
      the relationship with the total hardness and edematous change. STUDY DESIGN: Ten
      healthy volunteers performed sustained bilateral biting at 20% of maximal
      voluntary contraction for 10 min. The SE and magnetic resonance (MR) scans of the
      masseter muscles were performed before, immediately after, and 10 min after
      exercise. The masseter muscle elasticity index (MEI) ratio, muscle thickness, and
      intramuscular soft and hard areas distribution were evaluated on SE images. The
      signal to noise ratio (SNR), indicating the water content, was measured on MR
      images. RESULTS: The soft area ratio showed significant correlations with the
      water content expressed as SNR. The hard area ratio showed significant
      correlations with the total muscle hardness expressed as the MEI ratio.
      CONCLUSION: Intramuscular soft and hard areas could be used both clinically and
      experimentally.

PMID- 23953422
TI  - Mandibular bone structure, bone mineral density, and clinical variables as
      fracture predictors: a 15-year follow-up of female patients in a dental clinic.
AB  - OBJECTIVE: To compare three mandibular trabeculation evaluation methods, clinical
      variables, and osteoporosis as fracture predictors in women. STUDY DESIGN: One
      hundred and thirty-six female dental patients (35-94 years) answered a
      questionnaire in 1996 and 2011. Using intra-oral radiographs from 1996, five
      methods were compared as fracture predictors: (1) mandibular bone structure
      evaluated with a visual radiographic index, (2) bone texture, (3) size and number
      of intertrabecular spaces calculated with Jaw-X software, (4) fracture
      probability calculated with a fracture risk assessment tool (FRAX), and (5)
      osteoporosis diagnosis based on dual-energy-X-ray absorptiometry. Differences
      were assessed with the Mann-Whitney test and relative risk calculated. RESULTS:
      Previous fracture, gluco-corticoid medication, and bone texture were significant
      indicators of future and total (previous plus future) fracture. Osteoporosis
      diagnosis, sparse trabeculation, Jaw-X, and FRAX were significant predictors of
      total but not future fracture. CONCLUSION: Clinical and oral bone variables may
      identify individuals at greatest risk of fracture.

PMID- 23953423
TI  - Imaging findings of benign peripheral nerve sheath tumor in jaw.
AB  - OBJECTIVE: The aim of this study was to investigate the imaging characteristics
      of peripheral nerve sheath tumors (PNSTs) in the jaw. STUDY DESIGN: Imaging
      studies of 6 patients were retrospectively reviewed. Conventional radiography,
      computed tomography, and magnetic resonance imaging were performed in all
      patients. RESULTS: A fusiform lesion continuous with the nerve was observed in 2
      cases, with the tumor arising within the inferior alveolar canal. In the other 4
      cases, with the tumor arising outside the canal, the tumor had protruded and
      eroded into the bone. Protrusion was also present in 1 of the 2 cases, with the
      tumor arising within the canal. A target or fascicular sign was observed each in
      1 case. CONCLUSIONS: A fusiform lesion continuous with the nerve and a target or
      fascicular sign was only present in a few cases. The PNSTs, however, showed a
      tendency to protrude into the bone.

PMID- 23953424
TI  - Ultrasound evaluation of masseter muscle changes in stabilization splint
      treatment of myofascial type painful temporomandibular diseases.
AB  - OBJECTIVES: To detect whether stabilization splint (SS) treatment of painful
      myofascial type temporomandibular diseases (TMD) changes the masseter muscle
      morphology using ultrasound (US). STUDY DESIGN: Thirty-five patients with painful
      myofascial TMD receiving SS treatment were studied. Masseter thickness, length,
      internal echo-fibrillary structure and vascularization were evaluated using gray
      scale and power Doppler US just before and 3 months after the SS application.
      Visual analog scale (VAS) and mouth opening measurements were used to measure the
      outcome of treatment. RESULTS: A significant shortening in the masseter muscle
      length (R: -3.67 mm, P: .010; L: -3.97 mm, P: .005) and thickness (R: -0.93 mm,
      P: .005; L: -0.90 mm, P: .016) was noted. No change in the internal echo
      fibrillary structure or vascularization was detected. A significant decrease in
      VAS scores (Median: 5-0.5 P < .05) and mouth opening (42.77 +/- 7.86 mm to 38.69
      +/- 6.21, P < .05) was also detected. CONCLUSION: SSs modify and reduce the
      dimensions of masseter muscle.

PMID- 23953425
TI  - Dental perspectives in fibrous dysplasia and McCune-Albright syndrome.
AB  - McCune-Albright syndrome (MAS) is a rare multisystem disorder characterized by
      the triad of polyostotic fibrous dysplasia (FD), endocrine disorders, and cafe-au
      lait skin pigmentation. Ninety percent of MAS patients have FD lesions in the
      craniofacial area, resulting in significant orofacial deformity, dental
      disorders, bone pain, and compromised oral health. Maxillomandibular FD is also
      associated with dental developmental disorders, malocclusion, and high caries
      index. There are limited data on the outcomes of dental treatments in
      maxillomandibular FD/MAS patients, because clinicians and researchers have
      limited access to patients, and there are concerns that dental surgery may
      activate quiescent jaw FD lesions to grow aggressively. This report highlights
      current perspectives on dental management issues associated with
      maxillomandibular FD within the context of MAS. 

PMID- 23953426
TI  - Deep cervical granular cell tumor: an atypic location suggestive of neurogenic
      origin.
AB  - INTRODUCTION: Granular cell tumor (GCT), or Abrikossoff's tumor, is usually
      benign, with predominantly head-and-neck locations. Putative Schwann-cell origin
      is controversial. Treatment is surgical, due to risk of malignancy. CASE REPORT:
      A 41-year-old man presented with benign GCT in one of the deep cervical plexus
      roots, suggesting neurogenic origin. DISCUSSION: Surgical resection is important.
      Preoperative diagnosis is hindered by the ubiquity of the lesions and the poor
      specificity of imaging. Pathologic and immunohistochemical analysis is essential
      for definitive diagnosis.

PMID- 23953427
TI  - Exploring various modulation-sideband recoupling conditions of SHA+ sequence at
      fast MAS.
AB  - We explore modulation-sideband recoupling conditions of the (13)C-(13)C Second
      order Hamiltonian among Analogous nuclei plus pulse sequence (SHA+), and found
      that this sequence can be used in two different recoupling regimes. The first
      regime, nuR>Deltanuiso(max), is recommended for broad-band recoupling to avoid
      any rotational resonance broadening. In this regime, the spinning speed should be
      only slightly larger than Deltanuiso(max), to obtain the best transfer
      efficiency. The second regime, nuR<Deltanuiso(max), can be used to observe long
      range constraints with lower spinning speed, which increases the transfer
      efficiency, and may allow using bigger rotors to increase the S/N ratio. 

PMID- 23953428
TI  - Recent advances in the search for novel 5-lipoxygenase inhibitors.
AB  - 5-Lipoxygenase (5-LO) is an important enzyme of the arachidonic acid cascade and
      catalyses with the help of FLAP, the 5-LO-activating protein, the formation of
      bioactive leukotrienes (LTs). LTs are inflammatory mediators playing a
      pathophysiological role in different diseases such as asthma, allergic rhinitis
      as well as cardiovascular diseases and certain types of cancer. Up to now, only
      one 5-LO inhibitor is on the market, zileuton for the treatment of asthma. With
      the rising number of indications for anti-LT therapy, 5-LO inhibitor drug
      development becomes more and more important. This MiniReview gives an update on 5
      LO inhibitors currently under clinical development. Furthermore, the recent
      advances in the search for novel 5-lipoxygenase inhibitors with a focus on
      computational methods are summarized. Currently, licofelone is the compound with
      the highest clinical development status (completed phase III trials). 5-LO
      inhibitor screening programmes based on computational methods could deliver
      several promising drug-like new molecules. These activities can be expected to be
      driven by the newly resolved structure of human 5-LO in the future, enabling
      structure-based drug design. For the prospective drugs in late-stage clinical
      development, the future will show their clinical safety and efficacy in the
      particular diseases. 

PMID- 23953429
TI  - Balance in essential tremor during tandem gait: is the first mis-step an
      important finding?
AB  - Essential tremor (ET) is the most commonly diagnosed movement disorder. ET may
      cause substantial loss of motor skills and balance with advanced age. We compared
      abnormalities in tandem gait with daily activity and Fahn-Tolosa-Marin Tremor
      Rating Scale (FTMTRS) scores in 90 ET patients. All patients performed a 15-step
      tandem three times. The mean of first mis-steps was accepted as the tandem index
      (TI). The mean age was 61.4 +/- 17 years; the mean duration of tremor was 6.7 +/-
      4 years; and there were 36 men and 54 women. There was no significant difference
      for age or sex between patients and controls. Head (24.6%), jaw (5.5%), voice
      (11%), and tongue tremors (1.5%) were identified in ET patients. Rest (2.5%),
      postural (95%), and kinetic tremors (54%) were detected in the upper extremities.
      Postural tremor was found in the lower extremities of 5%. The mean TI was 8.3 +/-
      4 (median, 8) in ET patients, and 10.6 +/- 3.9 (median, 10) in controls (p=0.04).
      Correlation analysis of TI and FTMTRS scores showed tandem gait was significantly
      correlated with age, total tremor score, postural and kinetic extremity tremor,
      writing, drawing, pouring, feeding, and working scores. Linear regression showed
      a significant effect of age and FTMTRS score on TI. The decrease in balance
      control is apparent with advancing age. Balance disorders were more pronounced in
      ET patients. Although first mis-step in tandem gait is not as detailed as dynamic
      balance tests, it can be a simple method for detecting balance disorders.

PMID- 23953430
TI  - Genetic and biochemical findings in Chinese children with Leigh syndrome.
AB  - This study investigated the genetic and enzymological features of Leigh syndrome
      due to respiratory chain complex deficiency in Chinese patients. The clinical
      features of 75 patients were recorded. Mitochondrial respiratory chain enzyme
      activities were determined via spectrophotometry. Mitochondrial gene sequence
      analysis was performed in 23 patients. Five core pedigrees were investigated via
      restriction fragment length polymorphism and gene sequencing. Psychomotor
      retardation (55%), motor regression (20%), weakness (29%), and epilepsy (25%)
      were the most frequent manifestations. Sixty-four patients (85.3%) had isolated
      respiratory complex deficiencies: complex I was seen in 28 patients (37.3%);
      complex II, seven (9.3%); complex III, six (8%); complex IV, ten (13.3%); and
      complex V, 13 patients (17.3%). Eleven patients (14.7%) had combined complex
      deficiencies. Mitochondrial DNA mutations were detected in 10 patients. Eight
      point mutations were found in mitochondrial structural genes: m.4833A>G in ND2,
      m.10191T>C in ND3, m.12338T>C and m.13513G>A in ND5, m.14502T>C and m.14487T>C in
      ND6, m.8108A>G in COXII, and m.8993T>G in ATPase6. Three mutations were found in
      tRNA genes: m.4395A>G in tRNA-Gln, m.10454T>C in tRNA-Arg, and m.5587T>C in tRNA
      Ala. One patient and their mother both had the m.12338T>C and m.8993T>C
      mutations. In conclusion, mitochondrial respiratory chain complex I deficiency
      and structural gene mutations frequently occur in Chinese Leigh syndrome
      patients. 

PMID- 23953431
TI  - Adjunctive cryotherapy for pigmentary keratitis in dogs: a study of 16 corneas.
AB  - OBJECTIVE: To assess whether soft cryotherapy (dimethylether, isobutene, and
      propane) can remove pigmentation of the cornea that has accumulated under
      different conditions when conventional therapy has been unsuccessful. ANIMALS
      STUDIED: Nine dogs with unilateral or bilateral corneal pigmentation (16 eyes)
      were included based on progressive corneal pigmentation that was unresponsive to
      long-term etiological treatment. The dogs had keratoconjunctivitis sicca or
      chronic superficial keratitis. PROCEDURES: A cryogen of 95% dimethylether, 3%
      isobutane, and 2% propane was applied to the pigmented areas of each cornea under
      anesthesia. Initial corneal pigmentation and changes were documented over the
      entire study period using a grading scheme and clinical photographs. RESULTS:
      Most of the pigment deposits were gone by 5-15 days after cryosurgery.
      Postoperatively, the dogs showed some corneal edema and corneo-conjunctival
      inflammation, and three dogs had superficial corneal ulcers; these symptoms had
      resolved by 1 month after the procedure. Follow-up for more than 90 days was
      available in five dogs (nine corneas), and we observed total or partial
      repigmentation when the underlying disease was not controlled. A new cryotherapy
      procedure was successfully performed in two of these dogs. CONCLUSIONS: Given the
      sensitivity to cold of melanocytes, cryotherapy is a viable adjunctive treatment
      for refractory severe corneal pigmentation. Etiological treatment remains
      necessary to prevent pigmentation from rapidly reappearing. Only a few dogs were
      followed for more than 90 days; further study is necessary to evaluate the long
      term safety and efficacy of soft cryotherapy.

PMID- 23953432
TI  - Determination of 90Sr traces in medical 90Y after separation on DGA column.
AB  - A new analytical procedure for (90)Sr determination in freshly milked (90)Y from
      a (90)Sr/(90)Y generator is described. To a solution containing 125 mg of Sr a
      200 to 400 MBq sample of (90)Y is added and strontium is separated from (90)Y
      using DGA column of 1 mL volume. (90)Sr is recovered in a yield close to 100% and
      counted in a liquid scintillation spectrometer (LSC). The separated strontium is
      slightly contaminated with (90)Y in the range from 7 to 19% of (90)Sr activity.
      The separation and counting can be completed within 30 min. The detection limit
      in 900 s counting time is equal to about 0.2 Bq. This corresponds to (90)Sr/(90)Y
      activity ratio of 10(-8) level.

PMID- 23953433
TI  - A facile label-free electrochemiluminescence biosensor for target protein
      specific recognition based on the controlled-release delivery system.
AB  - This paper described a novel label-free electrochemiluminescence assay for target
      protein based on a controlled delivery system. Iron oxide magnetic mesoporous
      silica nanocontainers were prepared by using a general procedure. The prepared
      magnetic mesoporous silica nanocontainers were applied to load the guest
      molecules [Ru(bpy)3](2+). Aptamers were used as gatekeepers on the pore outlets
      of the nanocontainers. In the presence of target proteins, the specific aptamer
      protein interactions were employed as triggers for uncapping the pores and
      releasing the guest molecules from the nanocontainers. The amount of the guest
      molecule [Ru(bpy)3](2+) released from the magnetic mesoporous silica
      nanocontainers was monitored by the electrochemiluminescence assay. The results
      show that the releasing amount of [Ru(bpy)3](2+) is proportional to the thrombin
      concentration in the range of 0.6 pM-0.8 nM with a detection limit of 0.5 pM
      (S/N=3). The present work demonstrates that the fabricated nanocontainer using
      aptamer as the cap is a highly sensitive and selective key-in lock gating system
      for the label-free ECL biosensor.

PMID- 23953434
TI  - Analysis of perfluorooctane sulfonate and perfluorooctanoic acid with a mixed
      mode coating-based solid-phase microextraction fiber.
AB  - A novel mixed-mode coating-based solid-phase microextraction (SPME) fiber was
      prepared by chemical bonding dimethyloctadecyl [3-(trimethoxysilyl) propyl]
      ammonium chloride and 3-(trimethoxysilyl)-1-propanamine, the sol-gel precursors,
      on an anodized Ti wire, aiming to effectively adsorb perfluorooctane sulfonate
      (PFOS) and perfluorooctanoic acid (PFOA). The anodized Ti wire with uniform TiO2
      nanotube arrays provides high mechanical strength and strong adhesion to the
      mixed-mode coating. The prepared fiber shows excellent organic solvent stability
      due to the covalent bonding between the coating and the fiber, and significantly
      higher extraction efficiency than the commercial fibers, 100 MUm
      polydimethylsiloxane and 85 MUm polyacrylate fiber, due to the synergistic
      extraction effects of the coating functional groups. Good linearity (R(2)=0.9994
      for PFOS, R(2)=0.9992 for PFOA) was obtained with detection limits of 2.5 and 7.5
      pg mL(-1) for PFOS and PFOA, respectively. Recoveries were in the range of 88%
      102%. The proposed method was successfully applied in the analysis of PFOS and
      PFOA in a local river with the results of 0.05 and 0.06 ng mL(-1), respectively.

PMID- 23953435
TI  - Simultaneous and automated monitoring of the multimetal biosorption processes by
      potentiometric sensor array and artificial neural network.
AB  - In this communication, a new methodology for the simultaneous and automated
      monitoring of biosorption processes of multimetal mixtures of polluting heavy
      metals on vegetable wastes based on flow-injection potentiometry (FIP) and
      electronic tongue detection (ET) is presented. A fixed-bed column filled with
      grape stalks from wine industry wastes is used as the biosorption setup to remove
      the metal mixtures from the influent solution. The monitoring system consists in
      a computer controlled-FIP prototype with the ET based on an array of 9 flow
      through ion-selective electrodes and electrodes with generic response to divalent
      ions placed in series, plus an artificial neural network response model. The
      cross-response to Cu(2+), Cd(2+), Zn(2+), Pb(2+) and Ca(2+) (as target ions) is
      used, and only when dynamic treatment of the kinetic components of the transient
      signal is incorporated, a correct operation of the system is achieved. For this
      purpose, the FIA peaks are transformed via use of Fourier treatment, and selected
      coefficients are used to feed an artificial neural network response model. Real
      time monitoring of different binary (Cu(2+)/ Pb(2+)), (Cu(2+)/ Zn(2+)) and
      ternary mixtures (Cu(2+)/ Pb(2+)/ Zn(2+)), (Cu(2+)/ Zn(2+)/ Cd(2+)), simultaneous
      to the release of Ca(2+) in the effluent solution, are achieved satisfactorily
      using the reported system, obtaining the corresponding breakthrough curves, and
      showing the ion-exchange mechanism among the different metals. Analytical
      performance is verified against conventional spectroscopic techniques, with good
      concordance of the obtained breakthrough curves and modeled adsorption
      parameters. 

PMID- 23953436
TI  - Identification of selenium-containing proteins in HEK 293 kidney cells using
      multiple chromatographies, LC-ICPMS and nano-LC-ESIMS.
AB  - Our previous studies using HeLa and HEK 293 cells demonstrated that
      selenomethionine, SeMet, exerts more of an antagonistic effect on arsenic than
      other selenium species. These studies attributed the antagonistic effect of SeMet
      to decreased levels of reactive oxygen species, ROS, changes in protein
      phosphorylation and possible incorporation of SeMet into proteins. The present
      study employs a metallomics approach to identify the selenium-containing proteins
      in HEK 293 cells raised with SeMet. The proteins were screened and separated
      using two dimensional high performance liquid chromatography (HPLC)-inductively
      coupled plasma mass spectrometry (ICPMS), size exclusion chromatography (SEC) and
      reversed-phase chromatography (RPC). The Se-containing proteins were identified
      by peptide mapping using nano-HPLC-Chip-electrospray ionization mass spectrometry
      (ESIMS). 

PMID- 23953437
TI  - Ultrasound assisted dialysis of semi-permeable membrane devices for the
      simultaneous analysis of a wide number of persistent organic pollutants.
AB  - A new procedure based on ultrasound assisted dialysis (UAD) for the simultaneous
      and quantitative extraction of a wide number of persistent organic pollutants
      (POPs) such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls
      (PCBs) or some other organochlorinated pesticides (OCPs) contained in semi
      permeable membrane devices (SPMDs) has been developed. This extraction technique
      combines the advantages of the organic solvent dialysis (OSD) and the speed of
      the ultrasound assisted extraction. The extraction was performed in an ultrasound
      bath for 32 min placing the SPMD in a glass flask covered with 80 mL of hexane.
      This set-up is able to extract simultaneously up to 8 samples. The proposed
      method entails good repeatabilities (RSD 2-13%) and recoveries (around 100% for
      almost every analyte). Limits of detection were at ng SPMD(-1) level and enough
      for the determination of the target analytes in a slightly polluted aquatic
      environment, as it was tested by successfully comparing the OSD to the proposed
      methodology. Therefore, the results obtained show that the UAD can be a good
      alternative for the extraction of POPs in SPMDs as it requires short extraction
      times and solvent volumes, and provides a cleaner extract for the subsequent
      clean-up step. Moreover, it fits better than the OSD to the general requirements
      of Green Chemistry.

PMID- 23953438
TI  - Eco-friendly sonoluminescent determination of free glycerol in biodiesel samples.
AB  - This paper proposes a flow-batch methodology for the determination of free
      glycerol in biodiesel that is notably eco-friendly, since non-chemical reagents
      are used. Deionized water (the solvent) was used alone for glycerol (sample)
      extractions from the biodiesel. The same water was used to generate water
      cavitation sonoluminescence signals, which were modulated by the quenching effect
      associated with the amount of extracted glycerol. The necessarily reproducible
      signal generation was achieved by using a simple and inexpensive piezoelectric
      device. A linear response was observed for glycerol within the 0.001-100 mg/L
      range, equivalent to 0.004-400 mg/kg free glycerol in biodiesel. The lowest
      measurable concentration of free glycerol was estimated at 1.0 ug/L. The
      selectivity of the proposed method was confirmed by comparing the shape and
      retention of both real and calibration samples to standard solution
      chromatograms, presenting no peaks other than glycerol. All samples (after
      extraction) are greatly diluted; this minimizes (toward non-detectability)
      potential interference effects. The methodology was successfully applied to
      biodiesel analysis at a high sampling rate, with neither reagent nor solvent
      (other than water), and with minimum waste generation. The results agreed with
      the reference method (ASTM D6584-07), at a 95% confidence level.

PMID- 23953440
TI  - A label-free signal amplification assay for DNA detection based on exonuclease
      III and nucleic acid dye SYBR Green I.
AB  - We have developed a new fluorescence method for specific single-stranded DNA
      sequences with exonuclease III (Exo III) and nucleic acid dye SYBR Green I. It is
      demonstrated by a reverse transcription oligonucleotide sequence (target DNA, 27
      bases) of RNA fragment of human immunodeficiency virus (HIV) as a model system.
      In the absence of the target DNA, the hairpin-probe is in the stem-closed
      structure, the fluorescence of SYBR Green I is very strong. In the presence of
      the target DNA, the hairpin-probe hybridizes with the target DNA to form double
      stranded structure with a blunt 3'-terminus. Thus, in the presence of Exo III,
      only the 3'-terminus of probe is subjected to digestion. Exo III catalyzes the
      stepwise removal of mononucleotides from this terminus, releasing the target DNA.
      The released target DNA then hybridizes with another probe, whence the cycle
      starts anew. The signal of SYBR Green I decreases greatly. This system provides a
      detection limit of 160 pM, which is comparable to the existing signal
      amplification methods that utilized Exo III as a signal amplification nuclease.
      Due to the unique property of Exo III, this method shows excellent detection
      selectivity for single-base discrimination. More importantly, superiors to other
      methods based on Exo III, these probes have the advantages of easier to design,
      synthesize, purify and thus are much cheaper and more applicable. This new
      approach could be widely applied to sensitive and selective nucleic acids
      detection.

PMID- 23953439
TI  - Electrochemical biosensor based on silver nanoparticles-polydopamine-graphene
      nanocomposite for sensitive determination of adenine and guanine.
AB  - A multifunctional Ag nanoparticles (AgNPs)-polydopamine (Pdop)@graphene (Gr)
      composite was prepared by a simple and mild procedure. Gr was easily coated with
      Pdop at room temperature and then AgNPs was deposited by mildly stirring. The
      nanocomposite was characterized by scanning electron microscope (SEM) and
      transmission electron microscope (TEM). Guanine and adenine as model moleculars
      were employed to study their electrochemical responses at the Ag-Pdop@Gr
      composite modified electrode, which showed more favorable electron transfer
      kinetics than Gr modified glassy carbon and AgNPs modified glassy carbon
      electrodes. The Ag-Pdop@Gr modified electrode exhibited linear ranges of 0.04-50
      MUM and 0.02-40 MUM with detection limits of 4.0 nM and 2.0 nM for guanine and
      adenine, respectively. The developed method was applied for simultaneous
      determination of trace-level adenine and guanine in fish sperm. The results
      demonstrated that the AgNPs-Pdop@Gr nanocomposite was a promising substrate for
      the development of high-performance electrocatalysts for biosensing.

PMID- 23953441
TI  - Graphene matrix for signal enhancement in ambient plasma assisted laser
      desorption ionization mass spectrometry.
AB  - In this work, the signal intensity of ambient plasma assisted laser desorption
      ionization mass spectrometry (PALDI-MS) was significantly increased with graphene
      as matrix. The graphene functions as a substrate to trap analytes, absorb energy
      from the visible laser irradiation and transfer energy to the analytes to
      facilitate the laser desorption process. The desorbed analytes are further
      ionized by helium plasma and analyzed by MS. Compared with a traditional organic
      matrix, alpha-cyano-4-hydroxycinnamic acid (CHCA), graphene exhibited much higher
      desorption efficiency for most of the compounds benefitting from the strong
      optical absorption at 532nm. The performance has been confirmed by the facile
      analysis of more than forty compounds with various structures. Additionally, this
      method was successfully applied to distinguish three kinds of Chinese tea leaves
      by detecting the endogenous caffeine and theanine, which proved the utility,
      facility and convenience of this method for rapid screening of main components in
      real samples. 

PMID- 23953442
TI  - CNT-TiO2 coating bonded onto stainless steel wire as a novel solid-phase
      microextraction fiber.
AB  - A novel solid-phase microextraction (SPME) fiber based on carbon nanotubes
      titanium oxide (CNT-TiO2) composite coating bonded onto stainless steel wire was
      prepared via electroless plating and sol-gel techniques. The SPME coating was
      characterized by scanning electron microscopy and Raman microscopy. Coupled to
      gas chromatography (GC), the fiber was investigated with seven polycyclic
      aromatic hydrocarbons (PAHs) in direct-immersion mode. The SPME-GC analytical
      method was evaluated under optimized extraction conditions. Compared with other
      reports, higher sensitivity (LODs, 0.002-0.004 MUg L(-1)) and better linear range
      (0.01-100 and 0.01-200 MUg L(-1)) were obtained by the proposed method. The fiber
      exhibited high thermal stability to 300  degrees C and excellent durability in
      HCl and NaOH solutions. The as-established SPME-GC method was used to analyze the
      real water samples and satisfactory results were obtained.

PMID- 23953443
TI  - A squaraine and Hg(2+)-based colorimetric and "turn on" fluorescent probe for
      cysteine.
AB  - A novel squaraine derivative (SQ-1) was synthesized and characterized for the
      determination of cysteine. Binding with Hg(2+) as a fluorescent quencher to SQ-1
      leads to absorption and emission turn-off. More significantly, the SQ-1-Hg(2+)
      complex exhibits a dual-channel chromofluorogenic responses to biologically
      important cysteine with a high sensitivity and selectivity over other natural
      amino acids, along with a low detection limit of 36.7 nM.

PMID- 23953444
TI  - Highly selective and sensitive determination of deoxymiroestrol using a
      polyclonal antibody-based enzyme-linked immunosorbent assay.
AB  - Pueraria candollei-associated products are of interest to worldwide consumers for
      their rejuvenating and cosmetic purposes. In addition, clinical trials have
      supported the beneficial effects of P. candollei on the alleviation of menopausal
      symptoms. Deoxymiroestrol, which was reported as the most potent phytoestrogen in
      the tuberous root of P. candollei, exhibited potential as a biomarker of P.
      candollei-derived samples and products. A polyclonal antibody-based enzyme-linked
      immunosorbent assay (ELISA) was developed for deoxymiroestrol determination. The
      raised antibody bound specifically to deoxymiroestrol with very low cross
      reactivities of 1.26 and 0.42% to structurally related miroestrol and
      isomiroestrol, respectively. The linear range was 0.73-3000.00 ng mL(-1), and the
      coefficients of variation for both the intra- and inter-plate determinations were
      less than 5%. In samples spiked with a known amount of deoxymiroestrol, the
      recoveries were 99.82-102.58% in P. candollei samples and 98.07-106.33% in its
      products samples. In comparison with other analytical methods, the validated
      ELISA was comparable to published HPLC-UV methods for samples with high
      deoxymiroestrol content (R(2)=0.9993). Furthermore, ELISA can be used for samples
      with deoxymiroestrol concentrations that are too small to detect by HPLC and for
      conditions when other chemicals cause interference with chromatographic analysis.
      For the P. candollei-derived products, the preparations contained 0.154-10.998 ug
      g(-1) dry wt. Our ELISA successfully measured deoxymiroestrol content with high
      sensitivity, selectivity, accuracy and rapidity. Therefore, this ELISA showed
      potential for dosage standardization of P. candollei-associated samples.

PMID- 23953445
TI  - Quantitative determination of neurotransmitters, metabolites and derivates in
      microdialysates by UHPLC-tandem mass spectrometry.
AB  - The main objective of the present work is to study the time-course of rat brain
      neurotransmitters in vivo after an oral challenge with a nutritional ingredient
      or an external stimulus, such as a chemical agent. An ultrahigh performance
      liquid chromatography-tandem mass spectrometry method for the identification and
      quantification of neurotransmitters, metabolites and derivates in microdialysates
      from rat brain was previously developed. Betaine, glutamine, glutamic acid, gamma
      aminobutyric acid, phosphocholine, glycerophosphocholine, cytidine 5'
      diphosphocholine, choline, acetylcholine, dopamine, norepinephrine, serotonin,
      tyrosine, epinephrine, tryptophan and 5-hydroxyindoleacetic acid were selected as
      analytes. The method involves direct injection of samples of microdialysates from
      rat brain onto the chromatographic equipment and quantification with a triple
      quadrupole mass spectrometer detector using an electrospray ionization interface
      in positive mode. The limits of detection ranged from 0.1 to 50 ng mL(-1) and the
      limits of quantification from 0.3 to 200 ng mL(-1). The inter- and intra-day
      variability were lower than 15%. Recovery rates ranged from 85% to 115%.

PMID- 23953446
TI  - Solid phase extraction-preconcentration and high performance liquid
      chromatographic determination of 2-mercapto-(benzothiazole, benzoxazole and
      benzimidazole) using copper oxide nanoparticles.
AB  - This study introduces a novel method of solid phase extraction (SPE),
      preconcentration and HPLC determination of 2-mercaptobenzimidazole (2MBI), 2
      mercaptobenzoxazole (2MBO) and 2-mercaptobenzothiazole (2MBT) from an aqueous
      solution by a SPE cartridge loaded with copper oxide nanoparticles. Results
      demonstrated that copper oxide nanoparticles are quite efficient for extraction
      and preconcentration of trace amounts of these mercaptans at room temperature.
      The study also investigated the effects of parameters such as pH, buffer and its
      volume, electrolyte concentration, flow rate of the test solution, composition
      and volume of the desorbing solvent, accepted tolerable volume, amount of
      adsorbent, reusability of cartridges and evidence of some co-existing species on
      extraction and determination of the above mentioned mercaptans. The method showed
      good linearity for determination of these mercaptans in the range of 0.01-10 MUg
      mL(-1) with regression coefficients better than 0.9969. The limits of detection
      (LODs) evaluations were 0.0021, 0.0027 and 0.0019 MUg mL(-1) for 2MBT, 2MBO and
      2MBI, respectively. The relative standard deviations (RSDs) for 0.2 MUg mL(-1)
      and 5 MUg mL(-1) of the measured mercaptans were below 3.04% and 4.23%,
      respectively. Ramin Power Plant (3000 MW, Ahvaz, Iran) cooling water containing
      some 2MBT (as corrosion inhibitor) was used as the real sample. Recovery tests
      with spiked levels of 2MBT, 2MBI and 2MBO were carried out and satisfied results
      were obtained.

PMID- 23953447
TI  - 1H-13C NMR-based urine metabolic profiling in autism spectrum disorders.
AB  - Autism Spectrum Disorders (ASD) are a group of developmental disorders caused by
      environmental and genetic factors. Diagnosis is based on behavioral and
      developmental signs detected before 3 years of age with no reliable biological
      marker. The purpose of this study was to evaluate the potential use of a 2D NMR
      based approach to express the global biochemical signature of autistic
      individuals compared to normal controls. This technique has greater spectral
      resolution than to 1D (1)H NMR spectroscopy, which is limited by overlapping
      signals. The urinary metabolic profiles of 30 autistic and 28 matched healthy
      children were obtained using a (1)H-(13)C NMR-based approach. The data acquired
      were processed by multivariate orthogonal partial least-squares discriminant
      analysis (OPLS-DA). Some discriminating metabolites were identified: beta
      alanine, glycine, taurine and succinate concentrations were significatively
      higher, and creatine and 3-methylhistidine concentrations were lower in autistic
      children than in controls. We also noted differences in several other metabolites
      that were unidentified but characterized by a cross peak correlation in (1)H
      (13)C HSQC. Statistical models of (1)H and (1)H-(13)C analyses were compared and
      only 2D spectra allowed the characterization of statistically relevant changes
      [R(2)Y(cum)=0.78 and Q(2)(cum)=0.60] in the low abundance metabolites. This
      method has the potential to contribute to the diagnosis of neurodevelopment
      disorders but needs to be validated on larger cohorts and on other developmental
      disorders to define its specificity. 

PMID- 23953448
TI  - Stable isotope ratio measurements of Cu and Zn in mineral dust (bulk and size
      fractions) from the Taklimakan Desert and the Sahel and in aerosols from the
      eastern tropical North Atlantic Ocean.
AB  - Accurate characterization of the stable isotope composition of Cu and Zn in major
      global mineral dust sources and in aerosols is central to the application of
      these isotope systems to the studies of global geochemical processes and cycles.
      We test here for the first time Cu and Zn isotope ratios within a well-defined
      source-receptor setting on the continent-ocean interface and determine the
      isotope composition of (i) bulk surface soil dust samples from the Sahel region,
      (ii) individual size fractions of surface dust samples from the Taklimakan
      Desert, and (iii) aerosols collected in the equatorial eastern North Atlantic
      region. This is achieved reducing the blank contribution during the ion exchange
      step using small resin and acid volumes and using a second ion exchange passage
      to purify the Cu fraction. We find no significant correlation between size
      fractions and isotope ratios in the two samples analyzed from the Taklimakan
      Desert. Mass balance calculations suggest that isotope ratios of bulk samples are
      within the analytical precision of the <4 MUm size fraction and can be used to
      characterize atmospheric long range transport of Cu and Zn in mineral dust from
      the Taklimakan Desert. The <1 um size fractions of two aerosol samples collected
      over the equatorial eastern North Atlantic region have Cu and Zn isotope ratios
      that are different to Sahel surface soil dust suggesting important non-crustal
      sources, in line with calculated enrichment factors, and possibly of
      anthropogenic origin. Using previously reported delta(66)Zn values for
      anthropogenic emission from Europe, preliminary calculations suggest that up to
      55% of Zn arriving at the sampling points in the equatorial eastern North
      Atlantic region could be of anthropogenic origin.

PMID- 23953449
TI  - Layer-by-layer self-assembly xylenol orange functionalized CdSe/CdS quantum dots
      as a turn-on fluorescence lead ion sensor.
AB  - A new turn-on fluorescence sensor based on xylenol orange (XO) functionalized
      CdSe/CdS quantum dots (QDs) is developed for the determination of lead ion.
      CdSe/CdS QDs were first modified by mercaptoacetic acid (MAA). The MAA-modified
      QDs were then capped with the natural biopolymer chitosan and the negatively
      charged XO. The XO-functionalized QDs were formed via the layer-by-layer self
      assembly reaction. The fluorescence of the QDs was quenched by electron transfer
      mechanism after XO was bound to the QDs. Upon the addition of Pb(2+), a dramatic
      enhancement of the fluorescence intensity was observed, which resulted from the
      coordination between Pb(2+) and XO on QDs surface and the disruption of the
      electron transfer mechanism. Hence the fluorescence of the QDs was recovered. The
      recovery of the fluorescence intensity showed a good linear relationship with the
      concentration of Pb(2+) added from 0.05 to 6 MUmol L(-1). A detection limit of
      0.02 MUmol L(-1) was achieved. This method was successfully applied to the
      determination of lead in real samples with satisfactory results.

PMID- 23953450
TI  - High sensitive and selective HPTLC method assisted by digital image processing
      for simultaneous determination of catecholamines and related drugs.
AB  - A highly sensitive and selective thin layer chromatographic (TLC) method was
      developed for simultaneous determination of catecholamines and their related
      drugs using a new detection method and digital image processing of
      chromatographic plates. For the quantitative evaluation of the investigated
      compounds, the chromatographic separation was followed by spraying the plate with
      0.02% solution of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) in ethanol. The
      BioDit Thin Layer Chromatography (TLC) Scanner device and advanced specific
      software (ImageDecipher-TLC, Sorbfil TLC Videodensitometer and JustTLC) were used
      for the detection and quantification of chromatographic spots. For an accurate
      determination, the RGB colored images of the bright-white spots detected against
      a purple background were inverted and processed after their conversion into green
      scale. The results showed a strongly linear correlation between area (R(2)>0.99)
      and volume (R(2)>0.99) of spots and concentration of investigated compounds in
      all cases. The limit of detection (LOD) and the limit of quantification (LOQ)
      were below 49.3 ng/spot and 69.6 ng/spot respectively in all cases. The
      evaluation of the method was performed using different pharmaceutical samples
      spiked with the investigated amines and validated with respect to accuracy and
      precision.

PMID- 23953451
TI  - Highly sensitive and selective cartap nanosensor based on luminescence resonance
      energy transfer between NaYF4:Yb,Ho nanocrystals and gold nanoparticles.
AB  - Fluorescent detection is an attractive method for the detection of toxic
      chemicals. However, most chemosensors that are currently utilized in fluorescent
      detection are based on organic dyes or quantum dots, which suffer from
      instability, high background noise and interference from organic impurities in
      solution, which can also be excited by UV radiation. In the present research, we
      developed a novel NaYF4:Yb,Ho/Au nanocomposite-based chemosensor with high
      sensitivity (10 ppb) and selectivity over competing analytes for the detection of
      the insecticide cartap. This nanosensor is excited with a 970-nm laser instead of
      UV radiation to give an emission peak at 541 nm. In the presence of cartap, the
      nanocomposites aggregate, resulting in enhanced luminescence resonance energy
      transfer between the NaYF4:Yb,Ho nanocrystals and the gold nanoparticles, which
      decreases the emission intensity at 541 nm. The relative luminescence intensity
      at 541 nm has a linear relationship with the concentration of cartap in the
      solution. Based on this behavior, the developed nanosensor successfully detected
      cartap in farm produce and water samples with satisfactory results.

PMID- 23953452
TI  - Determination of mini-short tandem repeat (miniSTR) loci by using the combination
      of polymerase chain reaction (PCR) and microchip electrophoresis.
AB  - In this work, a simple and convenient method for the detection of mini-short
      tandem repeat (miniSTR) loci has been developed by the combination of polymerase
      chain reaction (PCR) and microchip electrophoresis (MCE). Degraded or inhibitor
      DNA greatly limited STR loci analysis. Therefore, The proper primers was designed
      as close as possible to the STRs region to produce smaller size STRs, and made
      the assay suitable for the destroyed samples. Two annealing temperatures were
      applied in one PCR procedure and the corresponding cycle numbers were studied to
      improve the sensitivity of PCR reaction. Under optimal conditions, 0.001 ng DNA
      templates were enough to generate miniSTRs. The relative standard deviations
      (n=3) of the size fifteen miniSTRs from DNA9947A ranged from 0.49% to 4.41%. The
      RSDs of concentrations were between 0.94% and 4.95%. Fifteen miniSTRs were also
      well produced from human hair, indicating that the method has great potential
      application in criminal identification and paternity testing.

PMID- 23953453
TI  - A label-free biosensor for DNA detection based on ligand-responsive G-quadruplex
      formation.
AB  - A facile and label-free assay with label-free molecular beacons (MBs) and
      fluorescent dye N-methyl mesoporphyrin IX (NMM) was developed for the detection
      of specific single-stranded DNA sequences. It was demonstrated by a reverse
      transcription oligonucleotide sequence (target DNA, 20 bases) of RNA fragment of
      human immunodeficiency virus (HIV) as model systems. In the absence of target
      DNA, the MBs were in the stem-closed form, the G-quadruplex structure could not
      form and the fluorescence signal of NMM was very low. In the presence of target
      DNA the MBs turned "Off" to "On", thus promoting the formation of G-quadruplex
      which could greatly enhance the fluorescence of NMM. This biosensor was simple in
      design, fast in operation, and more convenient and promising than other methods.
      It took less than 30 min to finish and its detection limit was 1.4 nM. No
      sophisticated experimental techniques or chemical modification for DNA sequences
      were required. This new approach could be widely applied to sensitive and
      selective nucleic acids detection.

PMID- 23953454
TI  - Preparation of a bifunctional pyrazosulfuron-ethyl imprinted polymer with
      hydrophilic external layers by reversible addition-fragmentation chain transfer
      polymerization and its application in the sulfonylurea residue analysis.
AB  - A new bifunctional pyrazosulfuron-ethyl imprinted polymer was synthesized by the
      combination of molecular imprinting technology and living radical polymerization.
      In the synthesis, the pyrazosulfuron-ethyl imprinted polymer was obtained by the
      reversible addition-fragmentation chain transfer (RAFT) precipitation
      polymerization followed by grafting poly(glyceryl monomethacrylate) (pGMMA) by
      the post-RAFT polymerization. In this research, we used polyethylene glycol (PEG)
      as the polymeric porogen in order to increase the porosity of the material which
      is a new porogen application in the precipitation polymerization. The imprinted
      polymer has selectivity for the template and ability of humic acids exclusion
      which has shown the merits of molecularly imprinted polymers and restricted
      access materials. An online solid-phase extraction/HPLC method for the analysis
      of three sulfonylurea residues in soil samples has been developed and validated.
      The recovery of 81-99% in the spiked levels of 40-200 MUg kg(-1) was obtained and
      the limit of detection (LOD) and limit of quantification (LOQ) were less than 4.8
      and 15.9 MUg kg(-1) respectively. The results demonstrated that this bifunctional
      material can be used for the efficient pyrazosulfuron-ethyl extraction in the
      sulfonylurea residue analysis from environmental samples.

PMID- 23953455
TI  - Non-destructive analyses on a meteorite fragment that fell in the Madrid city
      centre in 1896.
AB  - The historical Madrid meteorite chondrite fell in 1896 showing thin melt veins
      with a 65% of brecciated forsterite fragments surrounded by a fine grained matrix
      formed by troilite, chromite and Fe-Ni blebs. It exhibits a delicate iron infill,
      neo-formation of troilite in pockets and shock veins and neo-formation of Na
      feldspar formed at high temperature and fast quenching. The semi-quantitative
      mineral determinations were performed with IMAGEJ freeware and chemical mappings
      resulting in the following approximated compositions: olivine (~55%); augite
      (~10%); enstatite (~10%); plagioclase (~10%); chromite (~2%); troilite (~4%),
      kamacite-taenite alpha-gamma-(Fe, Ni) (~7%) and merrillite (~7%). The specimen
      was also studied by computer tomography, micro-Raman spectroscopy and spectral
      cathodoluminescence. X-ray diffraction patterns were also recorded in non
      destructive way on a polished surface because of the small size of the specimen.
      This combination of non-destructive techniques provides an improved knowledge on
      the Madrid-1896 meteorite compared to the previous study performed on the same
      specimen carried out twenty years ago by electron probe microanalysis and optical
      microscopy in destructive way. Limits of these techniques are the specimen's size
      in the analytical chambers and the threshold resolution of the microscopes
      analyzing shock veins micro-crystals.

PMID- 23953456
TI  - Ru(phen)3(2+) doped silica nanoparticle based immunochromatographic strip for
      rapid quantitative detection of beta-agonist residues in swine urine.
AB  - A Ru(phen)3(2+) doped silica nanoparticle based immunochromatographic strip was
      developed for the rapid and quantitative detection of five common beta-agonist
      (salbutamol (SAL), cimbuterol, terbutaline, clenbuterol, and brombuterol)
      residues in swine urine. The broad spectrum monoclonal antibodies generated by
      immunizing BALB/c mice with salbutamol conjugated cationic bovine serum albumin.
      The fluorescence intensities (FIs) of the strip on the test line (FIT) and
      control line (FIC) were determined using a strip reader. Parameters that
      influenced the antibody and antigen interaction on the test strip were
      investigated by recording FIT and FIC values, and the concept of FIT/FIC ratio
      was used to offset the inherent heterogeneity of the test strips and the effect
      of the sample matrix. Under optimal conditions, the linear range for the
      quantitative detection of SAL was 0.6-5.0 ng/ml with a half maximal inhibitory
      concentration at 1.78 ng/ml. The limit of detection for real swine urine was 0.43
      ng/ml. The recovery rates of the intraassay for spiked urine at SAL
      concentrations of 0.8, 1.5, and 3.5 ng/mL were 88.06%+/-3.75%, 95.77%+/-5.33%,
      and 94.06%+/-7.43%, whereas those for the interassay were 84.69%+/-5.0%, 95.06%+/
      9.3%, and 88.34%+/-7.71%, respectively. The developed quantitative method
      exhibited excellent agreement with a commercially available competitive enzyme
      linked immunosorbent assay kit for SAL-spiked urine samples, with a correlation
      of coefficient of 0.95 and a slope of 0.99 (n=36). The results indicated that the
      developed test strip enables sensitive, reproducible, and easily implementable
      screening for the rapid and quantitative detection of beta-agonist residues in
      swine urine.

PMID- 23953457
TI  - Liquid-solid extraction coupled with magnetic solid-phase extraction for
      determination of pyrethroid residues in vegetable samples by ultra fast liquid
      chromatography.
AB  - In this study, liquid-solid extraction coupled with magnetic solid-phase
      extraction was successfully developed for the extraction of pyrethroid residues
      in vegetable samples. The analytes were determined by ultra fast liquid
      chromatography. The pyrethroids were extracted by liquid-solid extraction and
      then adsorbed onto magnetic adsorbent. Magnetic adsorbent, C18-functionalized
      ultrafine magnetic silica nanoparticles, was synthesized by chemical
      coprecipitation, silanization and alkylation. The analytes adsorbed onto the
      magnetic adsorbent can be simply and rapidly isolated from sample solution with a
      strong magnet on the bottom of the extraction vessel. The extraction parameters,
      such as liquid-solid extraction solvent, liquid-solid extraction time, the amount
      of magnetic adsorbent, magnetic solid-phase extraction time and magnetic solid
      phase extraction desorption solvent, were optimized to improve the extraction
      efficiency. The analytical performances of this method, including linear range,
      detection limit, precision, and recovery were evaluated. The limits of detection
      for pyrethroid were between 0.63 and 1.2 ng g(-1). Recoveries obtained by
      analyzing the four spiked vegetable samples were between 76.0% and 99.5%. The
      results showed that the present method was a simple, accurate and high efficient
      approach for the determination of pyrethroids in the vegetable samples.

PMID- 23953458
TI  - Determination of chlorophenols in water by headspace solid phase microextraction
      ion mobility spectrometry (HS-SPME-IMS).
AB  - Chlorophenols (CPs) as persistent toxic compounds are of worldwide environmental
      concern. Usage of chlorinated phenols, especially pentachlorophenol (PCP), has
      been restricted or widely banned in many countries due to their possible adverse
      health effects even at low concentrations. Ion mobility spectrometry (IMS) has
      received increasing interest in environmental applications due to its unique
      characteristics, such as portability and speed of analysis. A range of sample
      introduction methods combined with IMS enable analysis from different
      environmental matrices. This study utilised headspace solid phase microextraction
      IMS (HS-SPME-IMS) in the determination of CPs from water samples. The extraction
      conditions were examined and the method was applied to real water samples. The
      developed method is suitable to detect CPs at milligram per liter level in water.
      Based on the results, SPME-IMS setup is feasible as an early warning system for
      water monitoring of pollutants present in drinking or surface water in case of
      environmental accidents or leakages. 

PMID- 23953459
TI  - Visible-light-driven photocatalytic and chemical sensing properties of SnS2
      nanoflakes.
AB  - This work demonstrated the successful and facile large-scale synthesis and
      characterizations of SnS2 nanoflakes. The detailed morphological studies revealed
      that the synthesized products were nanoflakes and were grown in large quantity.
      The XRD pattern and detailed compositional studies confirmed that the synthesized
      SnS2 nanoflakes were well-crystalline and possessing hexagonal SnS2 phase. The
      synthesized SnS2 nanoflakes were used as efficient photocatalysts for
      photocatalytic degradation and effective electron mediators for the fabrication
      of chemical sensor. The photocatalytic properties of SnS2 nanoflakes towards the
      photocatalytic degradation of Rhodamine B dye under visible light irradiation
      showed reasonably good degradation of ~61%. Moreover, the as-synthesized SnS2
      nanoflakes were used as efficient electron mediators for the fabrication of
      nitroaniline chemical sensor by simple I-V technique. Very high-sensitivity of ~
      505.82+/-0.02 mAcm(-2).(mole/L)(-1) and experimental detection limit of ~15*10(
      6) (mole/L) in a short response time of ~10.0 s with LDR in the range of 15.6*10(
      6)-0.5*10(-3) mole L(-1) were observed for the fabricated nitroaniline chemical
      sensor. The observed results indicated that the SnS2 nanoflakes can efficiently
      be used as visible-light-driven photocatalysts and the fabrication of ultra-high
      sensitive chemical sensors.

PMID- 23953460
TI  - Progress and recent advances in phosphate sensors: a review.
AB  - This review covers the progress made in the development of sensors for inorganic
      and organic phosphates that are significant pollutants within the environmental
      and biological systems. Phosphate sensors in the forms of amperometric,
      potentiometric enzyme electrodes, plant tissue electrode and screen printed
      electrode are described. Instrumental probes such as fluorescence,
      chemiluminescence, luminescence and potentiometric ion selective electrodes are
      also described. Recent efforts on the use of voltammetric, potentiometric and
      amperometric biosensors for the determination of phosphate are highlighted. 

PMID- 23953461
TI  - Probing trace Hg2+ in a microfluidic chip coupled with in situ near-infrared
      fluorescence detection.
AB  - A novel microfluidic chip coupled with near-infrared (NIR) fluorescence detection
      set-up was established for specific analysis of trace Hg(2+). Based on the NIR
      fluorescence changes caused by Hg(2+)-induced dissolution and aggregation of
      label-free single-strand DNA (ssDNA) wrapped single-walled carbon nanotubes
      (SWNTs), Hg(2+) in aqueous solution were detected sensitively and specifically in
      the microfluidic chips system. Due to the small device dimension effect as well
      as the high efficiency of microfluidic chips, the reagent volume reduced from 500
      MUL to 9 MUL and the minimum reaction time reaching the plateau was shortened
      from 60 min to 30 min, while the detection limit for Hg(2+) decreased from 10.5
      nM to 1.5 nM, compared with that of measured in regular Eppendorf tube. The idea
      of detecting NIR fluorescence spectra in microfluidic systems opens new avenues
      to optical analysis and bioassays in probing trace species.

PMID- 23953462
TI  - Simulated single-cycle kinetics improves the design of surface plasmon resonance
      assays.
AB  - Instruments based on the surface plasmon resonance (SPR) principle are widely
      used to monitor in real time molecular interactions between a partner,
      immobilized on a sensor chip surface and another one injected in a continuous
      flow of buffer. In a classical SPR experiment, several cycles of binding and
      regeneration of the surface are performed in order to determine the rate and the
      equilibrium constants of the reaction. In 2006, Karlsson and co-workers
      introduced a new method named single-cycle kinetics (SCK) to perform SPR assays.
      The method consists in injecting sequentially increasing concentrations of the
      partner in solution, with only one regeneration step performed at the end of the
      complete binding cycle. A 10 base-pair DNA duplex was characterized kinetically
      to show how simulated sensorgrams generated by the BiaEvaluation software
      provided by BiacoreTM could really improve the design of SPR assays performed
      with the SCK method. The DNA duplex was investigated at three temperatures, 10,
      20 and 30  degrees C, to analyze fast and slow rate constants. The results show
      that after a short obligatory preliminary experiment, simulations provide users
      with the best experimental conditions to be used, in particular, the maximum
      concentration used to reach saturation, the dilution factor for the serial
      dilutions of the sample injected and the duration of the dissociation and
      association phases. The use of simulated single-cycle kinetics saves time and
      reduces sample consumption. Simulations can also be used to design SPR
      experiments with ternary complexes.

PMID- 23953463
TI  - Identification of synthetic dyes in early colour photographs using capillary
      electrophoresis and electrospray ionisation-mass spectrometry.
AB  - Capillary electrophoresis with photodiode array detection (CE-PDA) and with
      electrospray ionisation-mass spectrometry (CE-ESI-MS) was used for the separation
      and the identification of 23 synthetic organic dyes, among those used in early
      20th century colour photographs such as autochromes. Both cationic and anionic
      dyes could be separated within 15min using a single CE-PDA method. The method was
      used as the basis to develop a CE-ESI-MS methodology through the optimisation of
      the relevant ESI and MS parameters. Sheath liquid composition, nebulising gas
      pressure, drying gas flow rate and drying gas temperature were found to influence
      the sensitivity of the detection. These parameters were optimised in positive and
      negative ion modes for cationic dyes and anionic dyes, respectively. The two
      analyses could be carried out successively on a single sample. In view of the
      application to cultural heritage objects, the CE-ESI-MS analytical procedure was
      applied to identify the dyes in a Filmcolor artefact, late version of the
      autochrome. The results complemented and enhanced current knowledge as four
      cationic dyes and three anionic dyes were identified. Four additional dyes are
      proposed as possibly present as traces. 

PMID- 23953464
TI  - Development of a one-step microwave-assisted extraction method for simultaneous
      determination of organophosphorus pesticides and fungicides in soils by gas
      chromatography-mass spectrometry.
AB  - A one-step microwave-assisted extraction (MAE) procedure was developed for the
      simultaneous extraction of organophosphorus pesticide and fungicide residues in
      soil which have been greatly used in agriculture. Parameters that could influence
      the MAE efficiency such as irradiation power, temperature, time and solvent were
      investigated, and extraction efficiencies in the range of 92.6-103.7% were
      obtained using 400 W (100% output) at 160  degrees C for 10 min with only 12 mL
      of acetone-hexane (2:1, v/v). The analytes in extracts were analyzed directly by
      gas chromatography-mass spectrometry (GC-MS) without any further cleanup. At 5
      and 50 ng g(-1) fortification levels for each analyte, the average recoveries
      obtained were ranged from 70.0% to 120.0% with relative standard deviation (RSD)
      between 0.2% and 14%. The method was linear over 1-250 ng g(-1) with a
      correlation coefficient (r(2)) between 0.9916 and 0.9966. The detection limits
      (S/N=3) were between 0.10 and 0.12 ng g(-1). The applicability of the method was
      demonstrated by analyzing field soil samples collected from six intensive
      horticultural sites in Ethiopia.

PMID- 23953465
TI  - Solid-contact Hg(II)-selective electrode based on a carbon-epoxy composite
      containing a new dithiophosphate-based ionophore.
AB  - The experimental results herein concern a novel ion-selective electrode
      manufactured with an inner solid contact based on a new ligand O,O'-(2,2'
      biphenylene)dithiophosphate pentyl (PenDTF). This electrode displays high
      selectivity toward the Hg(II) ion even in the presence of different divalent
      ions. The electrode also exhibited a good Nernstian response to Hg(II) (33.7+/
      1.0 mV decade(-1)) over an ample concentration range (5.3*10(-7)-1.0*10(-2) mol
      L(-1)), with a detection limit of (6.1+/-1.7)*10(-7) mol L(-1). As a result of
      design, the electrode can be used for many experiments, simply renewing its
      contact surface with emery paper, without giving rise to a significant response
      deviation, exhibiting a variation coefficient of 3%, capable of being tested
      within the 0-5 pH interval. The electrode was used satisfactorily as indicating
      electrode during the potentiometric titration of Hg(II) ions with EDTA.

PMID- 23953466
TI  - Detection of biothiols in human serum by QDs based flow injection "turn off-on"
      chemiluminescence analysis system.
AB  - In the present work, a flow injection (FI) "turn off-on" chemiluminescent method
      was developed for the determination of glutathione (GSH). Strong
      chemiluminescence (CL) signals were observed from the hydrogen peroxide and CdTe
      quantum dots (QDs) system under basic condition, addition of trace amount of
      Cu(II) could caused significant CL quenching of the CdTe QDs-H2O2 system. In the
      presence of biothiols, Cu(II) can be removed from CdTe QDs surface via forming
      Cu(II)-S bond with thiols, and the CL signal of CdTe QDs-H2O2 system was
      recovered. Thus, the CL signals of CdTe QDs-H2O2 system were turned off and on by
      the addition of Cu(II) and biothiols respectively, and a flow injection CL
      analysis system for the determination of biothiols was established. Under the
      optimum conditions, the CL intensity and the concentration of GSH have a good
      linear relationship in the range of 2.0*10(-9)-6.5*10(-7) mol L(-1)
      (R(2)=0.9993). The limit of detection for GSH is 1.5*10(-9) mol L(-1) (S/N=3).
      This method has been applied to detect GSH in human serum with satisfactory
      results.

PMID- 23953467
TI  - Dry-reagent nucleic acid biosensor based on blue dye doped latex beads and
      lateral flow strip.
AB  - In the manuscript, a quantitative lateral flow nucleic acid biosensor (Lateral
      flow nucleic acid biosensor, LFNB) based on blue dye doped latex beads was
      proposed and its feasibility for detecting deoxyribonucleic acid (DNA) in plasma
      was investigated. A 60-mer DNA sequence (T1) was selected as model to demonstrate
      the protocol. Blue dyes doped latex bead bearing DNA probe would be captured on
      the corresponding test line in the presence of target DNA, to form an evident
      blue band. Although qualitative tests are realized by observing the color change
      of the test zone, quantitative data are obtained by recording the optical
      responses of the test zone with a portable "Strip Reader" instrument
      conveniently. The strip has been applied for the detection of synthesized DNA
      sample in human plasma sample with a detection limit of 3.75 fmol. Interference
      was not evident even the target DNA was spiked with 50 MUL plasma which indicated
      the well shielding of the latex bead reporters and quantified chromatographic
      separations of unwanted materials of the strip comparing with traditional gold
      nanoparticle based LFNB platforms.

PMID- 23953468
TI  - Resolution of lysosomes in living cells with a ratiometric molecular pH-meter.
AB  - Intracellular acidic vesicles, constituted mostly by lysosomes, mediated a
      variety of biological events ranging from endocytosis, apoptosis, to cancer
      metastasis, etc. A chimeric molecular pH-meter (Lyso-DR), comprised of a dansyl
      fluorophore and proton activatable rhodamine-lactam, was prepared for ratiometric
      reporting of intralysosomal acidity. Exclusively confined in lysosomes, Lyso-DR
      exhibited pH dependent dual fluorescence emission bands which enable resolution
      of individual lysosomes in terms of acidity and quantitation of the overall
      intracellular lysosomal acidity, e.g. the lysosomal pH of HeLa cells is around pH
      5.0 whereas that of L929 cells is around pH 6.2. Lyso-DR effectively
      differentiated the lysosomal pH changes of cells undergoing apoptosis vs
      necrosis, suggesting its utility in investigations on lysosome involved
      biomedical processes. 

PMID- 23953470
TI  - Implementation of a SPR immunosensor for the simultaneous detection of the 22K
      and 20K hGH isoforms in human serum samples.
AB  - We have implemented a Surface Plasmon Resonance (SPR) immunosensor based on a
      sandwich assay for the simultaneous detection of the two main hGH isoforms, of 22
      kDa (22K) and 20 kDa (20K). An oriented-antibody sensor surface specific for both
      hormone isoforms was assembled by using the biotin-streptavidin system. The
      immunosensor functionality was checked for the direct detection of the 22K hGH
      isoform in buffer, which gave high specificity and reproducibility (intra and
      inter-assay mean coefficients of variation of 8.23% and 9% respectively). The
      selective determination of the 22K and 20K hGH isoforms in human serum samples in
      a single assay was possible by using two specific anti-hGH monoclonal antibodies.
      The detection limit for both hormone isoforms was 0.9 ng mL(-1) and the mean
      coefficient of variation was below 7.2%. The excellent reproducibility and
      sensitivity obtained indicate the high performance of this immunosensor for
      implementing an anti-doping test.

PMID- 23953469
TI  - Direct analysis of trichloropyridinol in human saliva using an Au nanoparticles
      based immunochromatographic test strip for biomonitoring of exposure to
      chlorpyrifos.
AB  - A portable immunochromatographic strip-based biosensor for direct detection of
      trichloropyridinol (TCP), a specific biomarker of exposure to chlorpyrifos, in
      human saliva sample is presented. In this approach, a series of immunoreactions
      was performed on the test strip, where the targeted analytes (TCP) bound to the
      Au nanoparticles-labeled antibodies on the conjugate pad to form analyte-Au
      antibody conjugates, and then free Au-labeled antibodies were captured by TCP-BSA
      in the test zone. Captured Au nanoparticles, increased with decreased levels of
      analytes, can be observed visibly without any equipment and later quantified by a
      colorimetric reader. Several experimental parameters were optimized including Au
      nanoparticle-to-TCP antibody coupling ratio, the amount of Au-labeled TCP
      antibody, immunoreaction time, the pretreatment of sample pad and the preparation
      of stock solution of Au-TCP antibody that realize sensitivity, selectivity and
      direct detection of TCP. Under optimal conditions, this biosensor displays a
      highly linear range of 0.625-20 ng/mL TCP, with a detection limit of 0.47 ng/mL.
      Moreover, the immunosensor was successfully used for direct analysis of human
      saliva sample without any pretreatment. These results demonstrate that this Au
      nanoparticles-based immunochromatographic test strip (ITS) provides a simple,
      accurate, and quantitative tool for TCP detection and holds a great promise for
      point-of-care and in-field analysis of other biomarkers.

PMID- 23953471
TI  - Application of poly (ethyleneimine) solution as a binding agent in DGT technique
      for measurement of heavy metals in water.
AB  - A 0.050 mol L(-1) solution of poly (ethyleneimine) (PEI), had been used as a
      novel binding agent of diffusive gradients in thin-films (DGT) technique (PEI
      DGT) for measuring the concentrations of labile Cu(2+), Cd(2+) and Pb(2+) in
      waters. The binding capacities of the PEI-DGT for Cu(2+), Cd(2+) and Pb(2+) were
      11.8, 10.2 and 10.6 MUmol L(-1), respectively. The performance of PEI-DGT was
      independence of pH in the range of 4-8 and ionic strength in the range from 1*10(
      4) to 0.1 mol L(-1) (as NaNO3). PEI-DGT could measure 104.7+/-5.2% of the total
      concentration of Cd(2+) (0.500 mg L(-1)), 95.2+/-4.3% of the total Cu(2+) (0.500
      mg L(-1)) and 99.2+/-3.4% of the total Pb(2+) (0.500 mg L(-1)) in synthetic
      solution. Effects of the ligands on the measurement of labile metals were also
      investigated in synthetic solutions containing the various concentrations of EDTA
      and humic acid. In EDTA solution, the concentrations of labile metals measured by
      PEI-DGT showed good agreement with the theoretical concentrations of free metal
      ions. In humic acid solution, the concentrations of labile metals measured by PEI
      DGT decreased with the increase of the concentrations of humic acid. Several DGT
      devices with various binding agents, including PEI, sodium polyacrylate and
      poly(4-styrenesulfonate) solution, were used for the measurement of labile
      fractions of Cu(2+), Cd(2+) and Pb(2+) in the spiked waters and in mine
      wastewaters. The results showed that the concentrations of labile metal measured
      by DGT devices with different binding agents could be significantly different,
      indicating that the labile fractions of metals were dependent on the binding
      strength of the binding agents with metals. By choosing binding agents, the
      useful information on the speciation and bioavailability of the analytes can be
      provided.

PMID- 23953472
TI  - Surface modified BaTiO3 nanoparticles as the matrix for phospholipids and as
      extracting probes for LLME of hydrophobic proteins in Escherichia coli by MALDI
      MS.
AB  - In this paper, we report the dual function of 12-hydroxy octadecanoic acid (HOA)
      modified barium titanate nanoparticles (BaTiO3 NPs) as the matrix for
      phospholipids (PLs) and as hydrophobic affinity probes for liquid-liquid
      microextraction (LLME) of hydrophobic proteins in Escherichia coli prior to their
      identification by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-MS). FT-IR, SEM and TEM were used for the characterization of
      the HOA-modified BaTiO3 NPs. The surface modified BaTiO3 NPs acted as
      multifunctional probes (as extracting probes and as the matrix) for the analysis
      of PLs by MALDI-MS. Compared to 2,5-dihydroxybenzoic acid (2,5-DHB), the HOA
      modified BaTiO3 NPs provided good PLs mass spectra with similar or improved
      signal-to-noise (S/N) ratio, which demonstrated the potentiality of HOA-modified
      BaTiO3 NPs as a PLs purpose matrix. This method was found to be linear in
      concentration ranges of 1.0-5.0 MUM and 1.0-10.0 MUM for L-A-phosphatidyl-l
      serine (PS) and L-A-phsophatidic acid sodium (PA) with correlation coefficient
      (R(2)) values from 0.9905 to 0.9987. The detection limits were 0.20-0.35 MUM and
      0.25-0.40 MUM for PS and PA, respectively. We also demonstrated the HOA-modified
      BaTiO3 NPs as extracting and as preconcentrating probes for the LLME of
      hydrophobic proteins in E. coli prior to their identification by MALDI-MS. Thus,
      the surface modified BaTiO3 NPs-assisted LLME coupled with MALDI-MS provides a
      simple methodology for the efficient extraction and determination of hydrophobic
      molecules in biological samples.

PMID- 23953473
TI  - Fabrication of paper-based devices by lacquer spraying method for the
      determination of nickel (II) ion in waste water.
AB  - A spraying method with lacquer was developed for the fabrication of paper-based
      devices. A patterned iron mask was initially placed on a filter paper and held
      tightly attached by a magnetic plate placed on the opposite side. After that,
      acrylic lacquer was sprayed on the filter paper to create a hydrophobic area
      while the hydrophilic area was protected with the iron mask. The optimal
      conditions for the fabrication of this device were studied including lacquer type
      and particle retention efficiency of filter paper. Gloss spray lacquer and filter
      paper No. 4 were chosen as optimal lacquer type and particle retention efficiency
      of filter paper, respectively. To evaluate its efficiency, the paper-based
      devices were used to determine nickel using electrochemical detection. Cu
      enhancer solution was employed to increase sensitivity of nickel determination
      with the optimal concentration of 4.5 ppm. Under the optimal conditions, linear
      range was observed in the range of 1-50 ppm with a coefficient of determination
      of 0.9971. The limit of detection (LOD) and the limit of quantitation (LOQ) were
      found to be 0.5 and 1.97 ppm, respectively. Moreover, these paper-based devices
      coupled with electrochemical detection were applied to determine nickel in waste
      water of a jewelry factory and compared to those obtained with inductively
      coupled plasma optical emission spectrometry (ICP-OES). The results indicated
      that there were no significant variations between this proposed method (4.15+/
      0.043 ppm) and the ICP-OES method (4.06+/-0.013 ppm). Therefore, this spraying
      method was found to be an excellent alternative for the fabrication of paper
      based devices due to its ease of use, affordability and simplicity.

PMID- 23953474
TI  - On-line sample preconcentration by sweeping and poly(ethylene oxide)-mediated
      stacking for simultaneous analysis of nine pairs of amino acid enantiomers in
      capillary electrophoresis.
AB  - This study proposes a sensitive method for the simultaneous separation and
      concentration of 9 pairs of amino acid enantiomers by combining poly(ethylene
      oxide) (PEO)-based stacking, beta-cyclodextrin (beta-CD)-mediated micellar
      electrokinetic chromatography (MEKC), and 9-fluoroenylmethyl chloroformate (FMOC)
      derivatization. The 9 pairs of FMOC-derivatized amino acid enantiomers were
      baseline separated using a discontinuous system, and the buffer vials contained a
      solution of 150 mM Tris-borate (TB), 12.5% (v/v) isopropanol (IPA), 0.5% (w/v)
      PEO, 35 mM sodium taurodeoxycholate (STDC), and 35 mM beta-CD, and the capillary
      was filled with a solution of 1.5 M TB, 12.5% (v/v) IPA, 35 mM STDC, and 35 mM
      beta-CD. Based on the difference in viscosity between the sample zone and PEO
      solution and because of the STDC sweeping, the discontinuous system effectively
      stacked 670 nL of the 9 pairs of FMOC-derivatized amino acid enantiomers without
      losing chiral resolution. Consequently, the limits of detection for the 9 pairs
      of FMOC-derivatized amino acid enantiomers were reduced to 40-60 nM. This method
      was successfully used to determine d-Tryptophan (Trp), l-Trp, d-Phenylalanine
      (Phe), l-Phe, d-Glutamic acid (Glu), and l-Glu in various types of beers.

PMID- 23953475
TI  - Rapid determination of baicalin and total baicalein content in Scutellariae radix
      by ATR-IR and NIR spectroscopy.
AB  - In this study methods for the quantification of baicalin and total baicalein in
      Scutellariae radix with near infrared (NIR) spectroscopy and attenuated-total
      reflectance mid-infrared (ATR-IR) spectroscopy in hyphenation with multivariate
      analysis were developed and compared. The reference analysis was performed by
      high performance liquid chromatography coupled to diode array detection (HPLC
      DAD). Different pretreatments like standard normal variate (SNV), multiplicative
      scatter correction (MSC), first and second derivative Savitzky-Golay were applied
      on the spectra to optimize the calibrations. A principal component analysis was
      performed with both spectroscopic methods to distinguish wild and cultivated
      samples. Quality parameters obtained for test-set calibration models of ATR-IR
      spectroscopy (baicalin: standard error of prediction (SEP)=1.31, ratio
      performance to deviation (RPD)=2.91 and R(2)=0.88; total baicalein: SEP=1.02,
      RPD=3.24 and R(2)=0.89) and NIR spectroscopy (baicalin: SEP=1.50, RPD=2.54 and
      R(2)=0.88; total baicalein: SEP=1.19, RPD=2.76 and R(2)=0.84) demonstrate that
      both spectroscopic techniques in combination with multivariate analysis are
      successful tools for the quantification of baicalin and total baicalein in
      Scutellariae radix, but it was found that ATR-IR spectroscopy provides higher
      accuracy in the given application. Furthermore it was proved that wild and
      cultivated samples can be distinguished by ATR-IR. 

PMID- 23953476
TI  - Two-column sequential injection chromatography for fast isocratic separation of
      two analytes of greatly differing chemical properties.
AB  - This paper deals with a novel approach to separate two analytes with different
      chemical properties and different lipophilicity. The newly described methodology
      is based on the two column system that was used for isocratic separation of two
      analytes with very different lipophilicity-dexamethasone and cinchocaine.
      Simultaneous separation of model compounds cinchocaine and dexamethasone was
      carried under the following conditions in two-column sequential injection
      chromatography system (2-C SIC). A 25*4.6 mm C-18 monolithic column was used in
      the first dimension for retention and separation of dexamethasone with mobile
      phase acetonitrile:water 30:70 (v/v), flow rate 0.9 mL min(-1) and consumption of
      1.7 mL. A 10*4.6 mm C-18 monolithic column with 5*4.6 mm C-18 precolumn was used
      in the second dimension for retention and separation of cinchocaine using mobile
      phase acetonitrile:water 60:40 (v/v), flow rate 0.9 mL min(-1) and consumption
      1.5 mL. Whole analysis time including both mobile phase's aspirations and both
      column separations was performed in less than 4 min. The method was fully
      validated and used for determination of cinchocaine and dexamethasone in
      pharmaceutical otic drops. The developed 2-C SIC method was compared with HPLC
      method under the isocratic conditions of separation on monolithic column (25*4.6
      mm C-18). Spectrophotometric detection of both compounds was performed at
      wavelength 240 nm. System repeatability and method precision were found in the
      range (0.39-3.12%) for both compounds. Linearity of determination was evaluated
      in the range 50-500 MUg mL(-1) and coefficients of determination were found to be
      r(2)=0.99912 for dexamethasone and r(2)=0.99969 for cinchocaine.

PMID- 23953477
TI  - Mercury compounds characterization by thermal desorption.
AB  - The ability to accurately determine metal mercury content and identify different
      mercury species in solid samples is essential for developing remediation and
      control strategies. The aim of the present study is to characterize mercury
      compounds based on thermal desorption. For this purpose a series of samples was
      prepared and the operational parameters-heating velocity, carrier gas-were
      optimized. Fifteen commercial mercury compounds were analyzed for use as
      fingerprints. The results of the study show that the identification of mercury
      species by the method of thermal desorption is possible. The temperature of
      desorption increased according to the following order
      HgI2<HgBr2<Hg2Cl2=HgCl2<Hg(CN)2<HgCl2O8.H2O<Hg(SCN)2<HgS
      (red)<HgF2<Hg2(NO3)2.2H2O<Hg(NO3)2.H2O<HgO (yellow, red)<Hg2SO4<HgSO4. A
      comparison of the estimated total mercury content with the mercury content
      calculated by integrating the area of the desorption curve shows that recoveries
      of 79-104% for HgS can be estimated. The proposed method represents a significant
      step forward in direct mercury analysis in solid samples.

PMID- 23953478
TI  - Animating platelet production adds physiological context.
AB  - Animating complex biological processes contextualizes them within their
      underlying physiology, identifies gaps in our mechanistic understanding, affirms
      the importance of continued research, and provides a bridge between academic
      scientists and the general public. Here, two videos illustrate the clinical value
      of and translate state-of-the-art research in platelet production. 

PMID- 23953479
TI  - The nucleolus: an emerging target for cancer therapy.
AB  - For over 100 years, pathologists have utilised an increase in size and number of
      nucleoli, the subnuclear site of ribosome synthesis, as a marker of aggressive
      tumours. Despite this, the contribution of the nucleolus and ribosomal RNA
      synthesis to cancer has been largely overlooked. This concept has recently
      changed with the demonstration that the nucleolus indirectly controls numerous
      other cellular functions, in particular, the cellular activity of the critical
      tumour suppressor protein, p53. Moreover, selective inhibition of ribosomal gene
      transcription in the nucleolus has been shown to be an effective therapeutic
      strategy to promote cancer-specific activation of p53. This article reviews the
      largely untapped potential of the nucleolus and ribosomal gene transcription as
      exciting new targets for cancer therapy. 

PMID- 23953480
TI  - Epigenetic modifications in trinucleotide repeat diseases.
AB  - Accumulating evidence supports the important role for epigenetic changes in
      modulating clinical parameters of complex disorders, including neurodegenerative
      disease. Several conditions, including fragile X syndrome and Huntington's
      disease are caused by trinucleotide repeat (TNR) expansions in or near specific
      genes. Highlighting the link between epigenetic disruption and disease phenotype,
      recent studies have established significant correlations between clinical
      features, expansion size, gene expression, the chromatin profile, and DNA
      methylation in regions surrounding the TNR. Given the debilitating and sometimes
      fatal consequences of TNR disorders, understanding how an altered epigenetic
      profile impacts clinical outcome warrants further attention, and could provide
      key insights for developing novel epigenetic therapies and biomarkers. This
      review presents the current evidence of epigenetic changes in several TNR
      diseases. 

PMID- 23953481
TI  - 'Pathway drug cocktail': targeting Ras signaling based on structural pathways.
AB  - Tumors bearing Ras mutations are notoriously difficult to treat. Drug
      combinations targeting the Ras protein or its pathway have also not met with
      success. 'Pathway drug cocktails', which are combinations aiming at parallel
      pathways, appear more promising; however, to be usefully exploited, a repertoire
      of classified pathway combinations is desirable. This challenge would be
      facilitated by the availability of the structural network of signaling pathways.
      When integrated with functional and systems level clinical data, they can be
      powerful in advancing novel therapeutic platforms. Based on structural knowledge,
      drug cocktails may tear into multiple cellular processes that drive
      tumorigenesis, and help in deciphering the interrelationship between Ras
      mutations and the rewired Ras network. The pathway drug cocktail paradigm can be
      applied to other signaling protein targets. 

PMID- 23953482
TI  - Nitrate reduction in geologically heterogeneous catchments--a framework for
      assessing the scale of predictive capability of hydrological models.
AB  - In order to fulfil the requirements of the EU Water Framework Directive nitrate
      load from agricultural areas to surface water in Denmark needs to be reduced by
      about 40%. The regulations imposed until now have been uniform, i.e. the same
      restrictions for all areas independent of the subsurface conditions. Studies have
      shown that on a national basis about 2/3 of the nitrate leaching from the root
      zone is reduced naturally, through denitrification, in the subsurface before
      reaching the streams. Therefore, it is more cost-effective to identify robust
      areas, where nitrate leaching through the root zone is reduced in the saturated
      zone before reaching the streams, and vulnerable areas, where no subsurface
      reduction takes place, and then only impose regulations/restrictions on the
      vulnerable areas. Distributed hydrological models can make predictions at grid
      scale, i.e. at much smaller scale than the entire catchment. However, as
      distributed models often do not include local scale hydrogeological
      heterogeneities, they are typically not able to make accurate predictions at
      scales smaller than they are calibrated. We present a framework for assessing
      nitrate reduction in the subsurface and for assessing at which spatial scales
      modelling tools have predictive capabilities. A new instrument has been developed
      for airborne geophysical measurements, Mini-SkyTEM, dedicated to identifying
      geological structures and heterogeneities with horizontal and lateral resolutions
      of 30-50 m and 2m, respectively, in the upper 30 m. The geological heterogeneity
      and uncertainty are further analysed by use of the geostatistical software TProGS
      by generating stochastic geological realisations that are soft conditioned
      against the geophysical data. Finally, the flow paths within the catchment are
      simulated by use of the MIKE SHE hydrological modelling system for each of the
      geological models generated by TProGS and the prediction uncertainty is
      characterised by the variance between the predictions of the different models.

PMID- 23953483
TI  - Parents' experiences and views of caring for a child with a tracheostomy: a
      literature review.
AB  - OBJECTIVES: To review the published/reported experiences and views of parents'
      whose child has had a tracheostomy. To date, no review has focused specifically
      on parents' experiences and views of having a child with a tracheostomy. METHODS:
      MEDLINE, CINAHL, PsycINFO and Embase were systematically searched from 1990 to
      2012 and a review of reference lists was conducted. The review draws on articles
      where parents' views of caring for their child's tracheostomy were either the
      sole focus of the research or where parental views of caring for their child's
      tracheostomy have been sought as a subsidiary aim. Studies relating to the aims
      of the review were examined using quality appraisal tools and in line with
      criteria for inclusion of studies. Studies were excluded if findings were about
      adults, studies that only focused on children's or sibling's views were not based
      on empirical work (e.g. literature reviews or expert commentary) or were not
      published in the English language. Findings were summarised under thematic
      headings. RESULTS: The systematic database search identified 442 citations of
      which 10 were eligible for inclusion in the review. Of those 10 studies six were
      quantitative and four qualitative. Only one paper published qualitative data
      specifically on parents' experiences about their tracheotomised child. The three
      main themes identified were parents' experiences of caregiving, their social
      experiences and experiences of service delivery of having a child with a
      tracheostomy. Although parents encountered emotional and social challenges, some
      positive responses to these challenges were reported. CONCLUSION: This review
      identifies a lack of qualitative research on parents' views of having a child
      with a tracheostomy. Issues surrounding parental management of tracheostomy
      require further investigation. This review has identified the need to elicit
      parents' longitudinal experiences of having a child with a tracheostomy.

PMID- 23953484
TI  - Effect of acrolein, a hazardous air pollutant in smoke, on human middle ear
      epithelial cells.
AB  - OBJECTIVE: Acrolein is a hazardous air pollutant. Tobacco smoke and indoor air
      pollution are the main causes of human exposure. Acrolein has been shown to cause
      cytotoxicity in the airways and induce inflammation and mucin production in
      pulmonary cells. We investigated whether acrolein caused cytotoxicity, induced
      inflammation or increased expression of mucin in immortalized human middle ear
      epithelial cell lines (HMEECs). METHODS: Cytotoxicity following acrolein
      treatment was investigated using the MTT assay, flow cytometry, and Hoechst 33342
      staining of HMEECs. We measured expression of inflammatory cytokines tumor
      necrosis factor (TNF)-alpha and cyclo-oxygenase (COX)-2 and the mucin gene MUC5AC
      using semi-quantitative real-time reverse transcriptase polymerase chain reaction
      (RT-PCR) and Western blotting. RESULTS: Exposure to >50 MUg/mL acrolein caused a
      decrease in cell viability. Acrolein induced apoptosis and necrosis at 50 MUg/mL.
      Acrolein at 5-50 MUg/mL increased expression of TNF-alpha and COX-2, as shown by
      RT-PCR and Western blotting. Acrolein exposure at 5-50 MUg/mL for 2-24h increased
      MUC5AC expression, as determined by RT-PCR. CONCLUSION: Acrolein decreased cell
      viability, induced an inflammatory response, and increased mucin gene expression
      in HMEECs. These findings support the hypothesis that acrolein, a hazardous air
      pollutant in tobacco smoke and ambient air, is a risk factor for otitis media.

PMID- 23953485
TI  - Intralesional injection of Pingyangmycin plus corticosteroids may be an effective
      treatment for cheilitis granulomatosa.
AB  - Cheilitis granulomatosa is a rare disease characterised by the recurrent labial
      swelling of one or both lips with the possibility of the condition to remain on a
      permanent basis. This kind of granulomatous, inflammatory disease may appear
      independently or be linked to a paralysis such as the facial and lingua plicata
      which then characteristic of the Melkersson-Rosenthal syndrome. Classically, a
      non-necrotizing granulomatous inflammation is seen at histologic examination.
      Many treatments have been tried. But as its high recurrence rate, the results
      were often disappointing. The major active component of Pingyangmycin is
      bleomycin A5. Currently, bleomycin has been proved to be a widely accepted
      treatment protocol for hemangiomas and lymphangioma. It has been proved that
      bleomycin could infiltrate prominently into lymphocytes and other inflammatory
      cells. Stromal connective tissue would proliferate markedly as the result of
      sclerotherapy. Oedema, lymphangiectasia and perivascular lymphocytic infiltration
      are always seen in cheilitis granulomatosa histologically. Therefore, we
      hypothesize that intralesional injection of Pingyangmycin plus corticosteroids
      may be a safe and effective treatment for cheilitis granulomatosa. The efficacy
      of this treatment modality is worthy of further investigation. 

PMID- 23953486
TI  - Plasmodium falciparum gametocytes: with a view to a kill.
AB  - Drugs that kill or inhibit the sexual stages of Plasmodium in order to prevent
      transmission are important components of malaria control programmes. Reducing
      gametocyte carriage is central to the control of Plasmodium falciparum
      transmission as infection can result in extended periods of gametocytaemia.
      Unfortunately the number of drugs with activity against gametocytes is limited.
      Primaquine is currently the only licensed drug with activity against the sexual
      stages of malaria parasites and its use is hampered by safety concerns. This
      shortcoming is likely the result of the technical challenges associated with
      gametocyte studies together with the focus of previous drug discovery campaigns
      on asexual parasite stages. However recent emphasis on malaria eradication has
      resulted in an upsurge of interest in identifying compounds with activity against
      gametocytes. This review examines the gametocytocidal properties of currently
      available drugs as well as those in the development pipeline and examines the
      prospects for discovery of new anti-gametocyte compounds.

PMID- 23953487
TI  - A proposal for a new design: the exposure-crossover design.

PMID- 23953488
TI  - The stepped wedge design does not inherently have more power than a cluster
      randomized controlled trial.

PMID- 23953489
TI  - Forefoot deformation during stance: does the forefoot collapse during loading?
AB  - This study presents a specific description of forefoot deformation during the
      stance phase of normal human walking based on the combined analysis of pressure
      and three-dimensional optoelectronic measurements. Forefoot deformation is
      measured in forty healthy subjects using (1) a six-camera motion capture system
      (sampled at 250 Hz) tracking five reflective skin markers attached to the
      forefoot, (2) a pressure platform (sampled at 500 Hz) and (3) a forceplate
      (sampled at 1250 Hz). Forefoot deformation is characterized by the forefoot
      width, the mediolateral metatarsal arch height and the plantar pressure under the
      metatarsal heads. Using this setup, a typical pattern of forefoot motion is
      described during stance phase: From a flexible, compliant configuration at the
      beginning of stance phase, characterized by a decrease in mediolateral metatarsal
      arch height and a controlled increase in forefoot width, the forefoot turns into
      a stable configuration during midstance. Subsequently, the increase in
      mediolateral arch height and the decrease in forefoot width describe the
      transformation into a tight configuration during final stance. This transfer from
      a compliant into a rigid configuration through stance phase rejects the idea of
      the forefoot as a collapsing structure under increased loading.

PMID- 23953490
TI  - Elevated asymmetric dimethylarginine levels predict short- and long-term
      mortality risk in critically ill patients.
AB  - OBJECTIVE: Serum concentrations of asymmetric dimethylarginine (ADMA), an
      endogenous inhibitor of nitric oxide synthase, may contribute to endothelial
      dysfunction and organ failure in sepsis. We aimed at investigating ADMA levels as
      a potential diagnostic or prognostic biomarker in critically ill patients.
      METHODS: Two hundred fifty-five patients (164 with sepsis, 91 without sepsis)
      were studied prospectively upon admission to the medical intensive care unit
      (ICU) and on day 7, in comparison to 78 healthy controls. ADMA serum
      concentrations were correlated with clinical data and extensive laboratory
      parameters. Patients' survival was followed up for up to 3 years. RESULTS: ADMA
      serum levels were significantly elevated in critically ill patients at admission
      compared to controls. ADMA levels did not differ between patients with or without
      sepsis, but were closely related to hepatic and renal dysfunction, metabolism and
      clinical scores of disease severity. ADMA levels further increased during the
      first week of ICU treatment. ADMA serum levels at admission were an independent
      prognostic biomarker in critically ill patients not only for short-term mortality
      at the ICU, but also for unfavorable long-term survival. CONCLUSION: Serum ADMA
      concentrations are significantly elevated in critically ill patients, associated
      with organ failure and related to short- and long-term mortality risk.

PMID- 23953491
TI  - Early levels in blood of immunoglobulin M and natural killer cells predict
      outcome in nonseptic critically ill patients.
AB  - PURPOSE: Critical illness results in derangements of all components of the immune
      response. Nonetheless, most of the efforts evaluating immune status in critically
      ill patients have been done in the field of sepsis. Here we have evaluated the
      immunity status at intensive care unit (ICU) admission in a cohort of nonseptic
      critically ill patients and its influence on their outcome. MATERIAL AND METHODS:
      Ninety patients 18 years and older admitted to our ICU were studied for levels of
      immunoglobulin (Ig) G, IgM, IgA, CD3(+)CD4(+) T cells, CD3(+)CD8(+) T cells, B
      cells, natural killer (NK) cells, and C3 and C4 complement factors in peripheral
      blood in the next 24 hours after admission to the ICU. Patients with infection,
      sepsis, immunodeficiency, or concomitant immunosuppressive therapy were excluded.
      RESULTS: Levels of IgM, CD3(+) T cells, CD4(+) T cells, CD8(+) T cells, and B
      lymphocytes correlated inversely with age. In turn, levels of CD3(+) T cells,
      CD4(+) T cells, CD8(+) T cells, and C3 factor of the complement system correlated
      inversely with Acute Physiology and Chronic Health Evaluation II score.
      Multivariate Cox regression analysis censored at 28 days evidenced that levels of
      IgM played a protective role, whereas levels of NK cells behaved as a risk factor
      for mortality. Kaplan-Meier curves showed a cutoff of 58 mg/dL for IgM and 140
      cells/mm(3) for NK cells. CONCLUSIONS: In conclusion, our results demonstrate
      that IgM plays a protective role in critically ill patients with no sepsis,
      whereas NK cell counts seem to play a deleterious one. Aging and severity at
      admission affect levels of key factors of the immune system in the blood of these
      patients.

PMID- 23953492
TI  - Resources, attitudes and culture: an understanding of the factors that influence
      the functioning of accountability mechanisms in primary health care settings.
AB  - BACKGROUND: District level health system governance is recognised as an important
      but challenging element of health system development in low and middle-income
      countries. Accountability is a more recent focus in health system debates.
      Accountability mechanisms are governance tools that seek to regulate
      answerability between the health system and the community (external
      accountability) and/or between different levels of the health system
      (bureaucratic accountability). External accountability has attracted significant
      attention in recent years, but bureaucratic accountability mechanisms, and the
      interactions between the two forms of accountability, have been relatively
      neglected. This is an important gap given that webs of accountability
      relationships exist within every health system. There is a need to strike a
      balance between achieving accountability upwards within the health system (for
      example through information reporting arrangements) while at the same time
      allowing for the local level innovation that could improve quality of care and
      patient responsiveness. METHODS: Using a descriptive literature review, this
      paper examines the factors that influence the functioning of accountability
      mechanisms and relationships within the district health system, and draws out the
      implications for responsiveness to patients and communities. We also seek to
      understand the practices that might strengthen accountability in ways that
      improve responsiveness--of the health system to citizens' needs and rights, and
      of providers to patients. RESULTS: The review highlights the ways in which
      bureaucratic accountability mechanisms often constrain the functioning of
      external accountability mechanisms. For example, meeting the expectations of
      relatively powerful managers further up the system may crowd out efforts to
      respond to citizens and patients. Organisational cultures characterized by
      supervision and management systems focused on compliance to centrally defined
      outputs and targets can constrain front line managers and providers from
      responding to patient and population priorities. CONCLUSION: Findings suggest
      that it is important to limit the potential negative impacts on responsiveness of
      new bureaucratic accountability mechanisms, and identify how these or other
      interventions might leverage the shifts in organizational culture necessary to
      encourage innovation and patient-centered care.

PMID- 23953493
TI  - Continuing efficacy of milnacipran following long-term treatment in fibromyalgia:
      a randomized trial.
AB  - INTRODUCTION: Previous studies of long-term treatment response in fibromyalgia
      and other chronic pain states have generally been limited to approximately one
      year, leaving questions about the longer-term durability of response. The purpose
      of this study was to demonstrate continuing efficacy of milnacipran by
      characterizing changes in pain and other fibromyalgia symptoms after
      discontinuing long-term treatment. The mean length of milnacipran treatment at
      the time of randomized withdrawal was 36.1 months from initial exposure to
      milnacipran (range, 17.9 to 54.4 months). METHODS: After completing a long-term,
      open-label, lead-in study of milnacipran (which followed varying periods of
      exposure in previous studies), adult patients with fibromyalgia entered the four
      week open-label period of the current study for evaluation of ongoing treatment
      response. After the four-week period to confirm new baseline status, 151 patients
      taking milnacipran >=100 mg/day and reporting >=50% improvement from pre
      milnacipran exposure in Visual Analogue Scale (VAS) pain scores were classified
      as responders. These responders entered the 12-week, double-blind withdrawal
      period in which they were randomized 2:1 to continue milnacipran or switched to
      placebo. The prespecified primary parameter was loss of therapeutic response
      (LTR), defined as increase in VAS pain score to <30% reduction from pre
      milnacipran exposure or worsening of fibromyalgia requiring alternative
      treatment. Adverse events and vital signs were also monitored. RESULTS: Time to
      LTR was shorter in patients randomized to placebo than in patients continuing
      milnacipran (P < 0.001). Median time to LTR was 56 days with placebo and was not
      calculable for milnacipran, because less than half of the latter group of
      patients lost therapeutic response by study end. Additionally, 81% of patients
      continuing on milnacipran maintained clinically meaningful pain response (>=30%
      improvement from pre-milnacipran exposure), compared with 58% of patients
      switched to placebo (sensitivity analysis II; P < 0.001). The incidences of
      treatment-emergent adverse events were 58% and 47% for placebo and milnacipran,
      respectively. Mean decreases in blood pressure and heart rate were found in both
      groups, with greater decreases for patients switched to placebo. CONCLUSIONS:
      Continuing efficacy of milnacipran was demonstrated by the loss of effect
      following withdrawal of treatment in patients who received an average of three
      years of milnacipran treatment. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01014585.

PMID- 23953494
TI  - Adolescent urethral coitus: 2 cases and review of the literature.
AB  - BACKGROUND: Urethral coitus is a very rare finding in adolescent women. There are
      26 reported cases in the literature, but only two were in adolescents. Urethral
      coitus has been most commonly described in women with mullerian anomalies and
      less commonly in other unusual clinical circumstances. CASES: We report 2 cases
      of adolescent women with known mullerian anomalies who were unknowingly engaging
      in urethral coitus; 1 adolescent with known vaginal agenesis and VACTERL
      association and one 16-year-old with an oblique vaginal septum and non
      communicating functioning uterine horn. Both young women had significant urethral
      dilation at the time of examination under anesthesia. CONCLUSIONS: Urethral
      intercourse is rare but may have significant consequences. Ongoing follow-up,
      careful history, and physical examination in adolescent women with mullerian
      anomalies are important in order to avoid possible complications, particularly
      when they are contemplating sexual activity. A history of urinary incontinence,
      dyspareunia, and urinary tract infections in young women with mullerian anomalies
      should raise suspicion of urethral coitus. If possible, the mullerian anomaly
      should be corrected to allow vaginal intercourse and discontinuation of urethral
      coitus.

PMID- 23953495
TI  - Pelvic inflammatory disease in virginal adolescent females without tubo-ovarian
      abscess.
AB  - Pelvic inflammatory disease (PID) is an infection of the upper genital tract that
      is often caused by an ascending sexually transmitted infection. The complications
      of PID include pyosalpinx and tubo-ovarian abscess, infertility or ectopic
      pregnancy, and chronic pelvic pain of varying degrees. These sequelae underscore
      the importance of prompt diagnosis. We present 2 cases of PID in young women who
      denied any history of sexual activity or sexual abuse. Both cases were brought to
      the operating room with suspected appendicitis; however, laparoscopic evaluation
      revealed purulent fluid surrounding the pelvic organs. The literature is scant
      with respect to PID in the virginal patient. It is important to keep pelvic
      infection in the differential diagnosis of virginal patients who present with
      clinical symptoms of an acute abdomen. 

PMID- 23953496
TI  - Update on hepatocellular carcinoma breakthroughs: poly(ADP-ribose) polymerase
      inhibitors as a promising therapeutic strategy.
AB  - Hepatocellular carcinoma is the most common form of primary liver cancer which is
      the fifth most common cancer in men and the seventh in women and the third most
      common cause of cancer-related death worldwide. Only 10-20% of patients are
      eligible for curative treatments that result in a 5-year survival rate of 40% to
      70%. Therefore, the development of novel treatment options is necessary for the
      majority of patients and remains a considerable challenge. Conformal radiotherapy
      is used in certain circumstances and preliminary data obtained from phase 1/2
      trials are showing promising curative effects. There is thus an interest in
      identifying drugs that can be exploited to enhance radiation sensitivity that
      could be used in therapy and might improve clinical outcome. Small molecules
      inhibitors of poly(ADP-ribose) polymerases (PARP) are an example of a radio- and
      chemo-sensitizing drug, as well as being an efficient single agent treatment in
      certain genetic backgrounds. In this review, we discuss the role of PARP-1 in
      hepatocellular carcinoma and present the results of preclinical studies that have
      assessed the potential of PARP inhibition as a single treatment or combined with
      chemotherapy or radiotherapy for the treatment of hepatocellular carcinoma. 

PMID- 23953497
TI  - Improving treatment with methotrexate in rheumatoid arthritis-development of a
      multimedia patient education program and the MiRAK, a new instrument to evaluate
      methotrexate-related knowledge.
AB  - OBJECTIVES: To develop and test an evidence-based, multimedia patient education
      program (MPEP) about methotrexate (MTX) treatment for rheumatoid arthritis (RA)
      and a new measure of patient knowledge [Methotrexate in Rheumatoid Arthritis
      Knowledge test (MiRAK)]. METHODS: The content of the MPEP and MiRAK was guided by
      concept-mapping workshops with patients (N = 24), literature review, health
      professional, and expert linguistic input. The MPEP and MiRAK underwent multiple
      stages of testing and revision with patients and health professionals. The MiRAK
      was administered to RA patients (N = 169) and its properties examined using the
      Rasch analyses. A subset of respondents (N = 131) repeated the MiRAK to determine
      test-retest reliability. A before-after pilot study with patients who had
      recently started MTX (N = 31) tested responsiveness of the MiRAK and feasibility
      and acceptability of the MPEP. RESULTS: A DVD of 24-minutes duration was produced
      that presents detailed, evidence-based information about MTX. The Rasch analyses
      of the 60 MiRAK items revealed that these could be summated into a single score.
      The MiRAK had good model fit, supporting internal construct validity, good
      internal consistency (person separation index; 0.84), test-retest reliability
      (ICC; 0.89), and ability to detect change (ES; 2.38). The before-after study
      suggested that patients could self-administer the MPEP, with the majority finding
      it informative and easy to use. CONCLUSIONS: We developed a MPEP about MTX
      treatment for RA, which was found to be user-friendly and easily implementable.
      The MiRAK is a new scale, testing a broad spectrum of MTX knowledge. Analyses
      revealed strong evidence for its validity and reliability.

PMID- 23953498
TI  - Do current arterial hypertension treatment guidelines apply to systemic lupus
      erythematosus patients? a critical appraisal.
AB  - OBJECTIVE: Arterial hypertension (HTN) is reported to burden up to 74% of
      systemic lupus erythematosus (SLE) patients and contributes significantly to
      accelerated atherosclerosis and increased cardiovascular (CV) risk. Current HTN
      treatment guidelines have not incorporated lupus patients in their
      recommendations; whether these guidelines can be fully implemented in SLE is
      doubtful. METHODS: A critical appraisal of the existing HTN guidelines in regard
      to SLE is presented in this review, based upon clinical and experimental data.
      Particular issues addressed are the time of antihypertensive therapy initiation,
      the optimal blood pressure level, the antihypertensive agent of first-choice and
      the need for reduction of the total cardiovascular risk in SLE. RESULTS:
      Antihypertensive therapy should be recommended at levels of 140/90 mmHg (systolic
      and diastolic BP, respectively) in newly diagnosed lupus patients without overt
      target organ involvement. In the case of lupus nephritis (LN) or diabetes
      mellitus (DM), therapy should be implemented at lower levels, such as 130/80
      mmHg. Hypertensive lupus patients should be considered at high or very high CV
      risk and, consequently, the optimal BP level should be less than 130/80 mmHg.
      Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor
      blockers (ARBs) seem to be a safe and efficacious first-choice antihypertensive
      treatment in lupus patients. Total CV risk should be considered and co
      morbidities (dyslipidemia, antiphospholipid syndrome, etc.) should be managed
      promptly. CONCLUSIONS: Current HTN therapeutic guidelines, lacking data from
      large-scale clinical trials, may not adequately apply to SLE patients. The
      assessment of the aforementioned recommendations in randomized clinical trials is
      expected to confirm their value in reducing CV risk in SLE.

PMID- 23953499
TI  - Assessment of cyclic changes in the diameter of the aortic annulus using speckle
      tracking trans-esophageal echocardiography.
AB  - It is uncertain whether dynamic variation in the diameter of the aortic annulus
      occurs during the cardiac cycle in humans. The purpose of this study was to
      analyze cyclic changes of the aortic annulus using speckle-tracking trans
      esophageal echocardiography. The subjects were 40 patients with aortic stenosis
      and 40 controls. Absolute and relative changes in the diameter of the aortic
      annulus and the times at which the maximum and minimum diameters occurred during
      the cardiac cycle were determined using speckle-tracking trans-esophageal
      echocardiography. The maximum and minimum diameters were 22.9 +/- 2.7 and 20.0 +/
      2.9 mm, respectively, in controls. The change in diameter of the aortic annulus
      was 2.9 +/- 0.7 mm, and the relative change was 12.9 +/- 3.5%. The maximum aortic
      annulus diameter was reached at the onset of aortic valve opening, and the
      minimum diameter occurred in the rapid filling phase. The change in diameter of
      the aortic annulus was significantly smaller (2.2 +/- 0.6 mm vs. 2.9 +/- 0.7 mm,
      p < 0.0001), and the time to reach the maximum diameter was significantly longer
      (98.5 +/- 17.5 ms vs. 83.4 +/- 18.2 ms, p = 0.0004), in the aortic stenosis group
      than in the control group. The study found that dynamic changes of the aortic
      annulus occur in the cardiac cycle and can be measured using speckle-tracking
      trans-esophageal echocardiography. We also found that aortic stenosis has an
      effect on the extent and timing of these changes. This suggests that accurate
      assessment of aortic annulus diameter requires consideration of the timing of the
      cardiac cycle. 

PMID- 23953500
TI  - Large cell neuroendocrine carcinoma of the submandibular gland: case report and
      literature review.
AB  - Large cell neuroendocrine carcinoma (LCNEC) of the salivary gland is extremely
      rare. We report on a case of LCNEC in the submandibular gland. A 58-year-old male
      had a four-month history of an enlarging mass in his left submandibular region.
      He underwent lymph node resection and metastasis of LCNEC was suspected. Magnetic
      resonance imaging of the neck showed a solid submandibular gland tumor with
      marginal blurring. Positron-emission tomography and upper gastrointestinal
      endoscopy showed no evidence of malignancy other than in the left submandibular
      gland. He underwent left submandibular gland resection and left upper neck
      dissection. The final diagnosis was LCNEC of the submandibular gland; surgical
      margin was negative. Fourteen months later he is free of tumors. This is the
      first report of LCNEC of the submandibular gland. LCNEC of the salivary gland
      shows high-grade malignancy like that of the lung. According to past reports, two
      of four patients died despite multidisciplinary treatments. There are no standard
      treatments for LCNEC of the salivary glands. More studies are needed to define
      prognostic factors and establish therapeutic methods. 

PMID- 23953501
TI  - Filling the void: a coalescent numerical and experimental technique to determine
      aortic stent graft mechanics.
AB  - The presented study details a combined experimental and computational method to
      assess and compare the mechanical behavior of the main body of 4 different stent
      graft designs. The mechanical response to a flat plate compression and radial
      crimping of the devices is derived and related to geometrical and material
      features of different stent designs. The finite element modeling procedure is
      used to complement the experimental results and conduct a solution sensitivity
      study. Finite element evaluations of the mechanical behavior match well with
      experimental findings and are used as a quantitative basis to discuss design
      characteristics of the different devices. 

PMID- 23953502
TI  - Slack length of gastrocnemius medialis and Achilles tendon occurs at different
      ankle angles.
AB  - Although muscle-tendon slack length is a crucial parameter used in muscle models,
      this is one of the most difficult measures to estimate in vivo. The aim of this
      study was to determine the onset of the rise in tension (i.e., slack length)
      during passive stretching in both Achilles tendon and gastrocnemius medialis.
      Muscle and tendon shear elastic modulus was measured by elastography (supersonic
      shear imaging) during passive plantarflexion (0 degrees  and 90 degrees  of knee
      angle, 0 degrees  representing knee fully extended, in a random order) in 9
      participants. The within-session repeatability of the determined slack length was
      good at 90 degrees  of knee flexion (SEM=3.3 degrees  and 2.2 degrees  for
      Achilles tendon and gastrocnemius medialis, respectively) and very good at 0
      degrees  of knee flexion (SEM=1.9 degrees  and 1.9 degrees  for Achilles tendon
      and gastrocnemius medialis, respectively). The slack length of gastrocnemius
      medialis was obtained at a significantly lower plantarflexed angle than for
      Achilles tendon at both 0 degrees  (P<0.0001; mean difference=19.4+/-3.8 degrees
      ) and 90 degrees  of knee flexion (P<0.0001; mean difference=25.5+/-7.6 degrees
      ). In conclusion, this study showed that the joint angle at which the tendon
      falls slack can be experimentally determined using supersonic shear imaging. The
      slack length of gastrocnemius medialis and Achilles tendon occurred at different
      joint angles. Although reporting this result is crucial to a better understanding
      of muscle-tendon interactions, further experimental investigations are required
      to explain this result. 

PMID- 23953503
TI  - Do skeletal muscle properties recover following repeat onabotulinum toxin A
      injections?
AB  - Onabotulinum toxin A (BTX-A) is a frequently used treatment modality to relax
      spastic muscles by preventing acetylcholine release at the motor nerve endings.
      Although considered safe, previous studies have shown that BTX-A injections cause
      muscle atrophy and deterioration in target and non-target muscles. Ideally,
      muscles should fully recover following BTX-A treatments, so that muscle strength
      and performance are not affected in the long-term. However, systematic, long-term
      data on the recovery of muscles exposed to BTX-A treatments are not available,
      thus practice guidelines on the frequency and duration of BTX-A injections, and
      associated recovery protocols, are based on clinical experience with little
      evidence-based information. Therefore, the purpose of this study was to
      investigate muscle recovery following a six months, monthly BTX-A injection (3.5
      U/kg) protocol. Twenty seven skeletally mature NZW rabbits were divided into 5
      groups: Control (n=5), zero month recovery - BTX-A+0M (n=5), one month recovery -
      BTX-A+1M (n=5), three months recovery - BTX-A+3M (n=5), and six months recovery -
      BTX-A+6M (n=7). Knee extensor strength, muscle mass and percent contractile
      material in injected and contralateral non-injected muscles was measured at each
      point of recovery. Strength and muscle mass were partially and completely
      recovered in injected and contralateral non-injected muscles for BTX-A+6M group
      animals, respectively. The percent of contractile material partially recovered in
      the injected, but did not recover in the contralateral non-injected muscles. We
      conclude from these results that neither target nor non-target muscles fully
      recover within six months of a BTX-A treatment protocol and that clinical studies
      on muscle recovery should be pursued.

PMID- 23953504
TI  - Computational biomechanics of a lumbar motion segment in pure and combined shear
      loads.
AB  - Anterior shear has been implicated as a risk factor in spinal injuries. A 3D
      nonlinear poroelastic finite element model study of a lumbar motion segment L4-L5
      was performed to predict the temporal shear response under various single and
      combined shear loads. Effects of nucleotomy and facetectomy as well as changes in
      the posture and facet gap distance were analyzed as well. Comparison of the
      predicted anterior displacement and stiffness response with available
      measurements indicates satisfactory agreement. Under shear loads up to 400 N, the
      model predicted an almost linear displacement response. With increasing shear
      load and/or compressive preload, the stiffening behavior becomes evident,
      primarily due to stretched collagen fibers and greater facet interactions.
      Removal of the facets markedly decreases the segmental stiffness in shear and
      thus highlights the importance of the facets in resisting shear force; 61-87% of
      the applied shear force is transmitted through the facets depending on the
      magnitude of the applied shear and compressive preload. Fluid exudation during
      the day as well as reduced facet gap distance and a more extended posture yielded
      higher facet joint forces. The shear resistance of the motion segment remains
      almost the same with time despite the transfer of load sharing from the disc to
      facets. Large forces on facet joints are computed especially under greater
      compression preloads, shear forces and extension rotations, as time progresses
      and with smaller gap distances. The disc contribution on the other hand increases
      under larger shear loads, smaller compression preloads, flexed postures, larger
      facet gap distances and at transient periods.

PMID- 23953505
TI  - Time-course of venous wall biomechanical adaptation in pressure and flow
      overload: assessment by a microstructure-based material model.
AB  - Arteriovenous fistulae have been previously created by our group, through
      implantation of e-PTFE grafts between the carotid artery and jugular vein in
      healthy pigs, to gather comprehensive data on the time-course of the adapted
      geometry, composition, and biomechanical properties of the venous wall exposed to
      chronic increases in pressure and flow. The aim of this study was to
      mathematically assess the biomechanical adaptation of venous wall, by
      characterizing our previous in vitro inflation/extension testing data obtained 2,
      4, and 12 weeks post-fistula, using a microstructure-based material model. Our
      choice for such a model considered a quadratic function for elastin with a four
      fiber family term for collagen, and permitted realistic data characterization for
      both overloaded and control veins. As structural validation to the
      hemodynamically-driven differences in the material response, computerized
      histology was employed to quantitate the composition and orientation of collagen
      and elastin-fiber networks. The parameter values optimized showed marked
      differences among the overloaded and control veins, namely decrease in the
      quadratic function parameters and increase in the four-fiber family parameters.
      Differences among the two vein types were highlighted with respect to the
      underlying microstructure, namely the reduced elastin and increased collagen
      contents induced by pressure and flow-overload. Explicit correlations were found
      of the material parameters with the two basic scleroprotein contents,
      substantiating the material model used and the characterization findings
      presented. Our results are expected to improve the current understanding of the
      dynamics of venous adaptation under sustained pressure- and flow-overload
      conditions, for which data are largely unavailable and contradictory. 

PMID- 23953506
TI  - BMP-2 induced early bone formation in spine fusion using rat ovariectomy
      osteoporosis model.
AB  - BACKGROUND CONTEXT: Bone morphogenetic proteins (BMPs) enhance bone formation.
      Numerous animal studies have established that BMPs can augment spinal fusion.
      However, there is a lack of data on the effect of BMP-2 on spinal fusion in the
      osteoporotic spine. PURPOSE: To investigate whether recombinant human BMP-2
      (rhBMP-2) enhances spine fusion in an ovariectomized rat model. STUDY DESIGN: In
      vivo animal study. METHODS: Female Sprague-Dawley rats (n=60) were ovariectomized
      or sham operated and randomized into three groups: Sham (sham operated+fusion),
      ovariectomy (OVX) (OVX+fusion), and BMP (OVX+fusion+BMP-2). Six weeks after
      ovariectomy, unilateral lumbar spine fusion was performed using autologous iliac
      bone with/without rhBMP-2 delivered on a collagen matrix. For each group, gene
      expression and histology were evaluated at 3 and 6 weeks after fusion, and bone
      parameters were measured by microcomputed tomography at 3, 6, 9, and 12 weeks.
      RESULTS: Real-time reverse-transcription polymerase chain reaction at 3 weeks
      showed markedly increased expression of osteoblast-related markers (namely
      alkaline phosphatase, osteocalcin, Runx2, Smad1, and Smad5) in the BMP group
      compared with the other groups (p=.0005, .0005, .003, .009 and .012,
      respectively). Although the Sham and OVX groups showed both sparse and compacted
      bones between transverse processes at 6 weeks, the BMP group had a significantly
      larger bone mass within the fusion bed at 3 weeks and later. All rats in the BMP
      group had bridging bone at 3 weeks; at 12 weeks, bridging bones in the Sham and
      OVX groups were about 50% and 25%, respectively, of that in the BMP group.
      CONCLUSIONS: Recombinant human BMP-2 enhances spinal fusion in OVX rats and acts
      during early bone formation. Therapeutic BMP-2 may therefore improve the outcome
      of spinal fusion in the osteoporotic patient.

PMID- 23953507
TI  - An assessment of the Surgical Apgar Score in spine surgery.
AB  - BACKGROUND CONTEXT: The Surgical Apgar Score (SAS), a simple metric based on
      intraoperative heart rate, blood pressure, and blood loss, was developed in
      general and vascular surgery to predict 30-day major postoperative complications
      and mortality. No validation of SAS has been performed in spine surgery. PURPOSE:
      To perform a prospective assessment of SAS in spine surgery. STUDY DESIGN:
      Prospective study. PATIENT SAMPLE: Two hundred sixty-eight consecutive patients
      undergoing major and intermediate spinal surgeries in an 18-month period. OUTCOME
      MEASURES: Occurrence of major complications or death within 30 days of surgery.
      METHODS: Intraoperative parameters were registered, and SAS was calculated
      immediately after surgery. Outcome data were collected during a 30-day follow-up.
      The relationship between SAS and the outcomes was analyzed calculating relative
      risks (RRs) and likelihood ratios (LRs) for different scoring groups. A
      univariate logistic regression analysis was also performed. The discriminatory
      accuracy of SAS was evaluated calculating a C-statistic. RESULTS: Eighteen
      patients had >=1 complications (6.72%). Patients with SAS 9-10 exhibited a 1.64%
      complication rate (RR=1; LR=0.23), which monotonically augmented as the score
      decreased: (SAS 7-8=2.75%; RR=1.68; LR=0.39), (SAS 5-6=13.33%; RR=8.13; LR=2.14),
      (SAS<=4=17.39%; RR=10.61; LR=2.92). The regression analysis odds ratio was 0.66
      (95% confidence interval, 0.54-0.82), p<.01. The C-statistic was 0.77 (95%
      confidence interval, 0.66-0.88). CONCLUSIONS: Surgical Apgar Score allows risk
      stratification and has a good discriminatory power in patients undergoing spine
      surgery.

PMID- 23953508
TI  - Vertebroplasty increases compression of adjacent IVDs and vertebrae in
      osteoporotic spines.
AB  - BACKGROUND CONTEXT: Approximately 25% of vertebroplasty patients experience
      subsequent fractures within 1 year of treatment, and vertebrae adjacent to the
      cemented level are up to three times more likely to fracture than those further
      away. The increased risk of adjacent fractures postaugmentation raises concerns
      that treatment of osteoporotic compression fractures with vertebroplasty may
      negatively impact spine biomechanics. PURPOSE: To quantify the biomechanical
      effects of vertebroplasty on adjacent intervertebral discs (IVDs) and vertebral
      bodies (VBs). STUDY DESIGN: A biomechanics study was conducted using cadaveric
      thoracolumbar spinal columns from elderly women (age range, 51-98 years).
      METHODS: Five level motion segments (T11-L3) were assigned to a vertebroplasty
      treated or untreated control group (n=10/group) such that bone mineral density
      (BMD), trabecular architecture, and age were similar between groups. Compression
      fractures were created in the L1 vertebra of all specimens, and
      polymethylmethacrylate bone cement was injected into the fractured vertebra of
      vertebroplasty specimens. All spine segments underwent cyclic axial compression
      for 115,000 cycles. Microcomputed tomography imaging was performed before and
      after cyclic loading to quantify compression in adjacent VBs and IVDs. RESULTS:
      Cyclic loading increased strains 3% on average in the vertebroplasty group when
      compared with controls after 115,000 cycles. This global strain manifested
      locally as approximately fourfold more compression in the superior VB (T12) and
      two- to fourfold higher axial and circumferential deformations in the superior
      IVD (T12-L1) of vertebroplasty-treated specimens when compared with untreated
      controls. Low BMD and high cement fill were significant factors that explained
      the increased strain in the vertebroplasty-treated group. CONCLUSIONS: These data
      indicate that vertebroplasty alters spine biomechanics resulting in increased
      compression of adjacent VB and IVD in severely osteoporotic women and may be the
      basis for clinical reports of adjacent fractures after vertebroplasty.

PMID- 23953509
TI  - Global exponential stability of neutral high-order stochastic Hopfield neural
      networks with Markovian jump parameters and mixed time delays.
AB  - In this paper, a class of neutral high-order stochastic Hopfield neural networks
      with Markovian jump parameters and mixed time delays is investigated. The jumping
      parameters are modeled as a continuous-time finite-state Markov chain. At first,
      the existence of equilibrium point for the addressed neural networks is studied.
      By utilizing the Lyapunov stability theory, stochastic analysis theory and linear
      matrix inequality (LMI) technique, new delay-dependent stability criteria are
      presented in terms of linear matrix inequalities to guarantee the neural networks
      to be globally exponentially stable in the mean square. Numerical simulations are
      carried out to illustrate the main results. 

PMID- 23953510
TI  - Intradiploic hematoma of the frontal bone with secondary exophthalmos in a mare.
AB  - A 13-year-old cob mare was presented with exophthalmos and periocular swelling of
      the left eye. The diagnostic work-up included ocular ultrasound, sonographic
      examination through the thinned frontal bone, radiography, standing computed
      tomography of the skull and exploratory osteoplastic surgery. Histopathology was
      consistent with an organized hematoma. An intradiploic hematoma of the frontal
      bone was diagnosed 5 years after head trauma, with progressive expansion and
      deformation of the skull resulting in exophthalmos. Exophthalmos with facial bone
      deformation was the only clinical finding of intradiploic hematoma. Standing
      computed tomography (CT) aided the diagnosis to differentiate intradiploic
      hematoma from other, more common causes of facial bone distortion associated with
      paranasal sinus diseases. Intradiploic hematoma of possible traumatic origin is a
      differential diagnosis for sinonasal disease and exophthalmos in the horse.

PMID- 23953511
TI  - Treating post-traumatic tremor with deep brain stimulation: report of five cases.
AB  - BACKGROUND: Post-traumatic tremor is one of the most common movement disorders
      resulting from severe head trauma. However, literature regarding successful deep
      brain stimulation (DBS) treatment is scarce, resulting in ambiguity regarding the
      optimal lead location. Most cases support the ventral intermediate nucleus, but
      there is evidence to defend DBS of the zona incerta, ventral oralis
      anterior/posterior, and/or a combination of these targets. We report five
      patients with disabling post-traumatic tremor treated with DBS of the ventral
      intermediate nucleus and of the globus pallidus internus. METHODS: Patients were
      referred to the Vanderbilt Movement Disorders Division, and surgical intervention
      was determined by a DBS Multidisciplinary Committee. Standard DBS procedure was
      followed. RESULTS: Patients 1-4 sustained severe diffuse axonal injuries.
      Patients 1-3 underwent unilateral ventral intermediate nucleus DBS for
      contralateral tremor, while Patient 4 underwent bilateral ventral intermediate
      nucleus DBS. Patients 1-3 experienced good tremor reduction, while Patient 4
      experienced moderate tremor reduction with some dystonic posturing of the hands.
      Patient 5 had dystonic posturing of the right upper extremity with tremor of the
      left upper extremity. He was treated with bilateral DBS of the globus pallidus
      internus and showed good tremor reduction at follow-up. CONCLUSION: Unilateral or
      bilateral DBS of the ventral intermediate nucleus and bilateral DBS of the globus
      pallidus internus may be effective and safe treatment modalities for intractable
      post-traumatic tremor. Further studies are needed to clarify the optimal target
      for surgical treatment of post-traumatic tremor.

PMID- 23953512
TI  - MicroRNAs-novel therapeutic targets of eicosanoid signalling.
AB  - MicroRNAs (miRNAs) have emerged as important regulators in human physiological
      and pathological processes. We summarize the current knowledge about the role of
      miRNA involved in the control of inflammatory responses with a special focus on
      eicosanoid signalling. Cyclooxygenase 2 - the key enzyme of the prostanoid
      pathway - is regulated by different miRNAs such as miRNA-101, miR199a, miR26b and
      miR-146a. In contrast to this, the understanding of miRNA regulation on enzymes
      of the leukotriene biosynthesis is just at the beginning. The knowledge of miRNAs
      regulating enzymes of the eicosanoid pathway offers a new way for the development
      of new therapeutic concepts for the treatment of inflammatory diseases. 

PMID- 23953513
TI  - Microstructural characterization of TFA-MOD processed Y(1-x)Gd(x)Ba2Cu3O(7-y)
      with BaZrO3.
AB  - Y(1-x)Gd(x)Ba2Cu3O(7-y) with BaZrO3 film was fabricated on CeO2 buffered
      LaMnO3/ion beam assisted deposition-MgO/Gd2Zr2O7/Hastelloy C276TM substrates by
      the metal organic deposition process using trifluoroacetates. Both
      microstructural and analytical characterizations were performed by transmission
      electron microscopy with selected area electron diffraction method and energy
      dispersive X-ray spectroscopy. The thickness of Y(1-x)Gd(x)Ba2Cu3O(7-y) with
      BaZrO3 film was found approximately 700 nm and the film was composed of c-axis
      oriented Y(1-x)Gd(x)Ba2Cu3O(7-y) grains. Several types of particles,
      (Y,Gd)2Cu2O5, CuO and BaZrO3, were formed within the Y(1-x)Gd(x)Ba2Cu3O(7-y)
      film, whose sizes were about 100-200 nm for (Y,Gd)2Cu2O5 and CuO particles, and
      about 10-20 nm for BaZrO3 particles, respectively. In the Y(1-x)Gd(x)Ba2Cu3O(7-y)
      film, (Y,Gd)2Cu2O5 and CuO particles were dispersed heterogeneously, whereas
      BaZrO3 nanoparticles were found dispersed homogeneously with random orientation.
      In addition, electron tomographic observation was carried out to attain the three
      dimensional information of polyhedral BaZrO3 nanoparticles.

PMID- 23953514
TI  - Fatal acute liver failure after intravenous amiodarone administration.

PMID- 23953515
TI  - Revolution as a care plan: ethnography, nursing and somatic solidarity in
      Honduras.
AB  - While diagnosis is not within the biomedical scope of a nurse's work, assessment
      an inherently ethnographic exercise-is. In Honduras, as in the United States,
      nurses' proximity with patients, in terms of both time spent at the bedside and
      shared class identification (embodied as habitus), mean that nurses are often
      more effective than physicians in assessment and healing. Following the 2009 coup
      that brought a violently repressive regime to power in Honduras, subjectivation
      as citizen healers brought many nurses to assess patient health as a function of
      neoliberal and political violence. This assessment framed radical struggle that
      required nurses to block political violence with their own bodies as being a
      necessary part of patient care. Similarly, as ethnographer, I came to share with
      nurses and other Hondurans certain violent processes of subjectivation (albeit
      from a privileged subject position) that strengthened my solidarity with them as
      well as my deeply embodied investment in their care plan of organizing for
      radical social change. This paper examines the politicizing impact of the 2009
      coup on Honduran auxiliary and professional nurses and the ways in which nurse
      assessment and ethnographic analysis can overlap and combine in somatic and
      political solidarity with patients and others resisting state and political
      violence through their bodies. 

PMID- 23953516
TI  - Donor and recipient factors predicting time to graft failure following orthotopic
      liver transplantation: a transplant risk index.
AB  - INTRODUCTION: Much of the success of a transplant depends on appropriate matching
      of donor to recipient. METHODS: We validated the Donor Risk Index formula (DRI)
      using Mount Sinai Medical Center's 10-year cohort of over 1000 transplants.
      RESULTS: The DRI was significantly associated to graft failure with a relative
      risk (RR) of 1.32. Our cohort had an average DRI of 2.6 with survival of 83% at 3
      months, 79% at 1 year, and 70% at 3 years. The low rate of graft failure at a
      high DRI implies that there are other factors important in transplant pairing
      that are not considered in the DRI model. To determine these variables and
      quantify their importance, we constructed a Transplant Risk Index by identifying
      recipient and donor variables not captured in United Network for Organ Sharing
      (UNOS) that significantly correlated to graft failure. The most significant
      independent predictors of time to graft failure were donor age, weight, and peak
      serum sodium; ischemia time; and recipient creatinine, international normalized
      ratio, and hepatitis C infection. The coefficients for each of these factors were
      compiled into a Transplant Risk Index formula. A cutoff of 5 resulted in a graft
      survival rate of 86% at 3 months, 76% at 1 year, and 62% at 3 years using Kaplan
      Meier analysis. The predictive ability of the Transplant Risk Index was greater
      than the DRI or DMELD (the product of donor age and preoperative MELD) as
      assessed by the area under the receiver operating curve and the positive and
      negative predictive values. CONCLUSION: The Transplant Risk Index captures
      recipient factors and donor factors not captured in UNOS. Including these factors
      may improve the ability to predict good donor-recipient pairing.

PMID- 23953517
TI  - Novel approaches to preventing ischemia-reperfusion injury during liver
      transplantation.
AB  - Ischemia-reperfusion injury (IRI) results in profound allograft damage during
      liver transplantation. The process of IRI results in adenosine triphosphatase
      (ATP) depletion, the production of reactive oxygen species, and progressive
      tissue destruction. This injury process is accelerated on reperfusion in the
      recipient. Over the last decade an increasing body of literature has identified a
      complex interplay of molecular and cellular pathways responsible for causing IRI.
      This article summarizes recent developments, drawing on preclinical and clinical
      studies, focusing on how the detrimental effects of IRI can be prevented in liver
      transplantation. We present a balanced overview on how machine preservation
      technologies, the coagulation system, antioxidants, cytoprotective agents,
      cytokines, preservation solutions, and the innate and adaptive immune system can
      be targeted to prevent IRI in liver transplantation. 

PMID- 23953518
TI  - Medical students' knowledge and attitudes toward organ donation: results of a
      Dutch survey.
AB  - BACKGROUND: In the Netherlands, as in many other countries, a paucity of research
      exists on the attitudes and intentions of medical students toward organ donation.
      These students are of interest for the effect that increasing medical knowledge
      might have on the willingness to register as a donor. OBJECTIVE: To examine which
      factors determine medical students' willingness to register as donors. METHODS:
      We conducted a cross-sectional survey among medical students at the University of
      Amsterdam. Our questionnaire included questions on actual donor registration,
      motives, knowledge, and attitudes toward donation. To assess which factors were
      related to self-reported donor registration status, we conducted multivariate
      logistic regression analyses. RESULTS: We received 506 questionnaires (response
      rate at least 84%). The majority of respondents (80%) intended to donate organs,
      while 59% were registered. Self-reported medical knowledge and positive attitudes
      on donation were independently associated with registering as a donor. A rising
      study year was associated with registering as a donor; this could be explained by
      increasing medical knowledge and changing attitudes. CONCLUSION: The results of
      our study suggest that willingness to register as a donor increases with a rising
      level of knowledge on organ donation up to some minimal level.

PMID- 23953519
TI  - When organ donation from living donors serves as the main source of organ
      procurement: a critical examination of the ethical and legal challenges to
      Turkey's recent efforts to overcome organ shortage.
AB  - Despite the fact that Turkey has implemented a number of legislative and
      regulatory efforts to increase cadaveric donations, live donors still serve as
      the main source of organ procurement in this country. To address this problem,
      Turkey's regulatory authorities have sought to increase the number of brain death
      declarations. A new regulation issued in 2012 repeats the criteria for brain
      death that were first issued in 1993. This paper argues that these efforts are
      far from adequate owing to a number of complicated, ethical, and legal challenges
      that must be addressed to increase cadaveric organ donations. After examining
      these factors, which are completely neglected in current policies, we conclude
      that Turkey needs a realistic ethically justifiable organ procurement policy that
      must be supported by a framework of patient rights to implement the concept of
      patient autonomy and respect for human dignity in health care services as the
      primary goal. 

PMID- 23953520
TI  - Impact of patient characteristics and comorbidity profile on activation of
      patients on the kidney transplantation waiting list.
AB  - BACKGROUND: The aim of this study was to examine which demographic and
      comorbidity factors affected the activation of patients with end-stage renal
      disease on the national kidney transplantation waiting list. METHODS: This was a
      prospective cohort study across 13 transplantation centers in the United Kingdom
      from October 1, 2006 to September 30, 2007. Data were collected for all new adult
      patients (n = 1530) referred to the renal transplantation assessment clinic. The
      proportion of patients who were activated to the waiting list after a minimum one
      year follow-up was estimated. Factors influencing activation of patients on the
      waiting list were examined. RESULTS: A total of 872 (58.9%) patients were
      activated to the transplantation waiting list. The likelihood of activation to
      the transplantation waiting list was lower in patients older than 65 years (P =
      .021), nonwhite ethnicity (P < .0001), smokers (P < .0001), and those in whom
      diabetes was the cause of renal failure (P = .004). Multivariate analysis showed
      that there was an adverse impact of comorbidity such as ischemic heart disease (P
      = .003), diabetes (P = .006), and peripheral vascular disease (P = .007) on the
      likelihood of activation to the waiting list. CONCLUSION: Patient characteristics
      and comorbidity are associated with the probability of activation of patients to
      the waiting list.

PMID- 23953521
TI  - HLA-A, -B, -DRB1 allele and haplotype frequencies and comparison with blood group
      antigens in dialysis patients in the East Anatolia region of Turkey.
AB  - AIM: The first aim of that study was to investigate HLA class I and class II
      allele and haplotype frequencies in renal dialysis patients who live in East
      Anatolia in Turkey. Our second aim was to investigate whether there was a
      relationship between ABO and D blood group antigens and HLA alleles and
      haplotypes for the study group. MATERIALS AND METHODS: HLA class I and II
      polymorphisms in 408 renal dialysis patients were studied using sequence-specific
      primers (SSP) and sequence-specific oligonucleotides (SSO). Blood group antigens
      were detected by agglutination methods on microplates. RESULTS: A total of 16 HLA
      A, 34 HLA-B, and 15 HLA-DRB1 alleles were identified. The most frequent HLA-A
      alleles were HLA-A*02, HLA-A*24, and HLA-A*11. The most frequent HLA-B alleles
      were HLA-B*35, HLA-B*51, and HLA-B*44. In case of HLA-DRB1; HLA-DRB1*11, HLA
      DRB1*04, and HLA-DRB1*13 were first 3 alleles with higher frequency, in order. In
      the combination of those 3 alleles, the most frequent HLA-A-B-DRB1 haplotypes
      were HLA-A*02-B*51-DRB1*11, HLA-A*11-B*35-DRB1*11, A*24-B*35-DRB1*11. The
      frequency of ABO, D blood group antigens were observed as 0.168 for A Rh(+),
      0.019 for A Rh(-), 0.057 for B Rh(+), 0.013 for B Rh(-), 0.123 for O Rh(+), 0.014
      for O Rh(-), 0.018 for AB Rh(+), and 0.001 for AB Rh(-). While A Rh(+) samples
      with HLA-A*02 and HLA-DRB1*11 had the highest frequencies (0.067 and 0.088,
      respectively), O Rh(+) samples with HLA-B*51 had the highest frequency (0.06).
      CONCLUSION: According to haplotype frequencies HLA-A*02-B*51-DRB1*11 is also
      found at higher frequencies in Bulgarian and Armenian populations. In case of HLA
      associated diseases, the east Anatolian population could be susceptible to
      myastenia gravis, Behcet's disease, and systemic sclerosis due to the high
      frequencies of HLA-A*24, HLA-B*51, and HLA-DRB1*11 respectively. We did not
      observe a correlation between blood group antigens and HLA alleles or haplotypes
      in renal dialysis patients.

PMID- 23953522
TI  - Evaluation of knowledge and behavior of and attitudes towards smoking cigarettes
      and using smokeless tobacco in patients with chronic renal failure.
AB  - BACKGROUND: Smoking can have negative effects on renal function in healthy
      individuals, which may result in kidney disease. To determine knowledge,
      behavior, and attitudes toward smoking cigarettes and using smokeless tobacco
      among patients with chronic renal failure, we sought to provide evidence for
      appropriate precautions and guidance for further research. METHODS: The study
      included 86.7% of 390 patients undergoing treatment for chronic renal failure who
      completed a 30-question instrument. RESULTS: Of the participants, 7.9% were
      smokers and 12.6% ex-smokers. Among the smokers, 61% said they wanted to quit and
      45% said they needed help to quit. Of the participants, 9.5% were using Maras
      powder, a type of smokeless tobacco. Of the smokeless tobacco users, 55.6% noted
      that they wanted to give it up. The rate of the participants smoking cigarettes
      and/or using smokeless tobacco was 17.4%. In addition, 38.9% of the participants
      said that they started to use smokeless tobacco to quit smoking cigarettes. Of
      the participants, 62.6% thought smoking was harmful to the kidneys. The rate of
      the passive smokers was 30.2%. Of the participants, 66.3% explained that they
      were exposed to smoke at home. CONCLUSIONS: Appropriate interventions should
      begin to help patients with chronic renal failure stop smoking and to prevent
      them from exposure to cigarette smoke. Smokers should be informed that using
      smokeless tobacco is not a way to stop smoking cigarettes. Education programs
      should be conducted to prevent people from using smokeless tobacco and to help
      smokeless tobacco users to quit their habit.

PMID- 23953523
TI  - A comparative, randomized trial of concentration-controlled sirolimus combined
      with reduced-dose tacrolimus or standard-dose tacrolimus in renal allograft
      recipients.
AB  - BACKGROUND: The clinical safety and efficacy of sirolimus plus reduced-dose
      tacrolimus was evaluated in de novo renal allograft recipients enrolled in a
      comparative, open-label study. METHODS: One hundred twenty-eight renal allograft
      recipients were randomly assigned (1:1) to receive reduced-dose tacrolimus plus
      sirolimus (rTAC) or standard-dose tacrolimus and sirolimus (sTAC) for 6 months.
      The primary efficacy endpoint was calculated creatinine clearance values at 6
      months. RESULTS: Demographic variables were similar between groups. At 6 months,
      mean (+/- standard deviation) calculated creatinine clearance was significantly
      improved in the rTAC group (63.8 vs 52.7 mL/min, P = .005), although mean serum
      creatinine values were not significantly different. Patient survival (95.2% and
      96.9%) and graft survival (93.7% and 98.5%) were similar between the rTAC and
      sTAC groups, respectively. Acute rejection rates were 17.5% with rTAC and 7.7%
      with sTAC (P = .095). CONCLUSIONS: The rTAC regimen provided effective
      immunosuppression and was associated with improved creatinine clearance. Adequate
      immunosuppressant exposure must be achieved in the early postoperative period to
      minimize the risk of acute rejection.

PMID- 23953524
TI  - Outcome of renal transplantation from deceased donors after cardiac death: a
      single-center experience from a developing country.
AB  - BACKGROUND: Limited information is available in the literature about the use of
      organs from donation after cardiac death (DCD) renal transplantation (RTx) from a
      developing country. MATERIAL AND METHODS: We report RTx outcome between DCD
      donors >=70 years (Group 1; n = 14; mean age, 75.7 +/- 5.81) and DCD donors <70
      years (Group 2; n = l9; mean age, 51.7 +/- 10.1) between January 1999 and January
      2012. The mean age of recipients was 39.5 +/- 14.7 years, 24 of whom were males.
      The mean donor age was 61.9 +/- 14.6 years, 21 of whom were males. All recipients
      received single-dose thymoglobulin induction followed by immunosuppression with a
      steroid, a calcineurin inhibitor, and mycophenolate mofetil or azathioprine.
      Statistical analysis used chi-square test and unpaired Student t test. Kaplan
      Meier curves were used for survival analysis. RESULTS: Over a mean follow-up of
      3.21 +/- 3.46 years, one-, five-, and ten-year, patient survival rates were 77%,
      67.4%, and 67.4%, respectively, and death-censored graft survival rates were
      85.7% for one, five, and ten years. Delayed graft function (DGF) was observed in
      36.4% (n = 12) with 12.1% (n = 4) biopsy-proven acute rejection (BPAR). Patient
      survival (P = .27), graft survival (P = .20), DGF (P = .51), and BPAR (P = .74)
      were similar in 2 groups. A total of 27.2% (n = 9) of patients died, mainly due
      to infections (n = 5). CONCLUSION: Given the widespread organ shortage, outcomes
      of controlled DCD renal transplantation has a potential to expand the donor pool
      and shorten the waiting list for RTx, encouraging the use of this approach even
      in low-income countries.

PMID- 23953525
TI  - Identification of the effects of aging-related gene-matrix metalloproteinase on
      allograft outcomes in kidney transplantation.
AB  - BACKGROUND: Aging plays a profound role in the ability of the kidney to function.
      Aging which varies among individuals, has been associated with the matrix
      metalloproteinase (MMP) 7 and 20 genes. This study was conducted to analyze
      correlations between polymorphisms of MMP genes [rs880197 in MMP7 (A>T) and
      rs1711437 in MMP20 (G>A)] and transplant outcomes in 235 recipients. METHODS:
      Transplant outcomes were evaluated according to the sum of the A alleles in the
      recipients and the donors. The group with a high number of A alleles (>=3) was
      compared with the group with a low number (<3). RESULTS: The group with a high
      number of MMP7 A alleles showed a lower risk of chronic tubulointerstitial lesion
      than the group with a low number (P = .009). The group with a high number of
      MMP20 A alleles had showed better long-term kidney function at 10 years after
      transplantation than the group with a low number (P = .026). Furthermore, the
      group with a high number of MMP20 A alleles showed a trend toward better graft
      survival compared with the group with a low number, especially among recipients
      followed for >1 year (P = .022). CONCLUSIONS: Polymorphisms of MMP7 and MMP20
      genes may be surrogate markers to predict long-term outcomes after kidney
      transplantation.

PMID- 23953526
TI  - The impact of socioeconomic deprivation on outcomes following renal
      transplantation in the West of Scotland.
AB  - BACKGROUND: Social deprivation is associated with increased mortality for
      patients on renal replacement therapy. Patients from lower socioeconomic
      categories have reduced access to transplantation. However, the impact of social
      deprivation on outcomes following renal transplantation is unknown. METHODOLOGY:
      We undertook a retrospective analysis of all patients undergoing renal
      transplantation at a single center serving the West of Scotland over the 10-year
      period 2000 to 2010 (n = 705). Postcode data permitted calculation of a Scottish
      Index of Multiple Deprivation (SIMD) score, which was analyzed in quartiles from
      0% to 25% (least deprived) to 75% to 100% (most deprived). Outcomes measures were
      graft loss, mortality, creatinine at 1 year, delayed graft function (DGF), and
      biopsy-proven acute rejection (BPAR). Kaplan-Meier survival analysis was
      undertaken (P < .05 is significant). Results are presented as percentages of the
      total population in SIMD quartiles 0% to 25%, 25% to 50%, 50% to 70%, and 75% to
      100%, respectively. RESULTS: Mean follow-up was 5.86 +/- 0.11 years. There was no
      difference in survival following renal transplantation depending on SIMD (89.6%,
      87%, 88.4%, 90.2%; P = .82). There was improved graft survival in the least
      socioeconomically deprived; however, this was not significant (80%, 69.9%, 74.1%,
      73.8%; P = .34). Similarly, there was a nonsignificant trend toward lower
      creatinine at 1 year in the least deprived patients (163.5 +/- 12.8, 211.7 +/-
      19.5, 170.2 +/- 9.8, 197.1 +/- 6.9; P = .07). There was no difference in rates of
      DGF (P = .47), primary nonfunction (P = .17), or BPAR (P = .97) depending on
      socioeconomic status. The proportion of patients undergoing living donor
      transplantation was similar across the range of SIMD (23.9%, 27.6%, 25.5%, 21.8%;
      P = .76). CONCLUSIONS: Social deprivation does not affect either graft or patient
      survival after renal transplantation. Additionally, it did not influence the rate
      of living donor renal transplantation in our patient population.

PMID- 23953527
TI  - Perceived health after kidney transplantation: a cross-sectional comparison of
      long-term and short-term cohorts.
AB  - Although increased longevity of grafts has led to a growing number of long-term
      kidney transplant recipients, knowledge about the perceived health of these
      patients remains limited. A cross-sectional sample of 609 patients (60% response)
      was stratified into a short-term (<=1 year), midterm (>1 and <=8 years), and long
      term cohort (>8 and <=15 years posttransplantation). Cohorts were compared for
      perceived health (Visual Analogue Scale of the EQ-5D), number of symptoms, and
      number of comorbidities by analysis of variance/covariance and multivariate
      regression analyses. Long-term patients reported more symptoms, (F[2, 606] =
      3.09, P = .046) and more comorbidities, (F[2, 588] = 4.75, P = .009) but similar
      levels of perceived health, (F[2, 550] = 2.37, P > .05). Furthermore, symptoms
      were less influential for perceived health among long- versus short-term (z = 
      2.08, P = .038) or midterm cohorts (z = -2.60, P = .009). Previously identified
      predictors of perceived health accounted for less variance in the long-term as
      opposed to short-term (z = 4.30, P < .001) and midterm cohort (z = 2.07, P =
      .039). Despite more symptoms and comorbidities, the perceived health of long-term
      kidney transplant recipients was comparable to the short- and midterm, possibly
      due to selective survival or patient adjustment. Because kidney function and
      symptoms were predominantly associated with short-term perceived health, there is
      an urgent need to identify variables associated with long-term perceived health. 

PMID- 23953528
TI  - Comparison of the effects of normal saline versus Plasmalyte on acid-base balance
      during living donor kidney transplantation using the Stewart and base excess
      methods.
AB  - BACKGROUND: Ischemia-reperfusion injury is an inevitable consequence of kidney
      transplantation, leading to metabolic acidosis. This study compared the effects
      of normal saline (NS) and Plasmalyte on acid-base balance and electrolytes during
      living donor kidney transplantation using the Stewart and base excess (BE)
      methods. METHODS: Patients were randomized to an NS group (n = 30) or a
      Plasmalyte group (n = 30). Arterial blood samples were collected for acid-base
      analysis after induction of anesthesia (T0), prior to clamping the iliac vein
      (T1), 10 minutes after reperfusion of the donated kidney (T2), and at the end of
      surgery (T3). In addition serum creatinine and 24-hour urine output were recorded
      on postoperative days 1,2, and 7. Over the first postoperative 7 days we recorded
      episodes of graft failure requiring dialysis. RESULTS: Compared with the
      Plasmalyte group, the NS group showed significantly lower values of pH, BE, and
      effective strong ion differences during the postreperfusion period (T2 and T3).
      Chloride-related values (chloride [Cl(-)], free-water corrected Cl(-), BEcl) were
      significantly higher at T1, T2, and T3, indicating hyperchloremic rather than
      dilutional metabolic acidosis. Early postoperative graft functions in terms of
      serum creatinine, urine output, and graft failure requiring dialysis were not
      significantly different between the groups. CONCLUSIONS: Both NS and Plamalyte
      can be used safely during uncomplicated living donor kidney transplantation.
      However, Plasmalyte more stably maintains acid-base and electrolyte balance
      compared with NS especially during the postreperfusion period.

PMID- 23953529
TI  - Outcomes of methicillin-resistant Staphylococcus aureus infection after kidney
      and/or pancreas transplantation.
AB  - BACKGROUND: The true extent of Methicillin-Resistant Staphylococcus aureus (MRSA)
      colonization and incidence of infection after solid organ transplantation in
      adults and children is not well-known. The aim of this study was to evaluate the
      incidence and the outcomes of MRSA infection following kidney and/or pancreas
      transplantation. MATERIAL AND METHODS: We reviewed the case notes of all patients
      who developed MRSA colonization and infection within the first year of
      transplantation between September 2002 and December 2009. The primary endpoint of
      this study was mortality. The secondary endpoints included morbidity, graft
      failure, and length of hospital stay. RESULTS: During the study period 1116
      transplantations were performed. MRSA colonization was detected in 14 patients
      (1.25%) and infection occurred in 6 cases (0.53%) post-transplantation. Graft
      failure was not associated with MRSA colonization/infection in any of the cases.
      The mortality rate attributed to MRSA was 10% (n = 2). The overall median length
      of stay was 16 days (range, 6-243 days). CONCLUSIONS: Our study demonstrates that
      the prevalence of MRSA colonization and infection in our unit is low in spite of
      immunosuppression. The incidence of MRSA infection was higher among patients who
      underwent pancreas transplantation. Patients who had MRSA colonization and then
      developed infection had higher morbidity and mortality rates.

PMID- 23953530
TI  - Genetic association of tumor necrosis factor-beta, interleukin-10, and
      interleukin-1 gene cluster polymorphism with susceptibility to pneumonia in
      kidney transplant recipients.
AB  - INTRODUCTION: Pneumonia remains a significant cause of morbidity and mortality
      after kidney transplantation. The present study was therefore conducted to
      investigate whether or not the polymorphisms of tumor necrosis factor (TNF)beta,
      interleukin (IL)-10, IL-1beta, and IL-1 receptor antagonist (IL-1ra) gene
      predicted the susceptibility to pneumonia within the first year after kidney
      transplantation. METHODS: Subjects comprised 33 kidney transplant recipients with
      pneumonia and 63 noninfected kidney transplant recipients. Genomic DNA from these
      96 kidney transplant recipients was extracted from peripheral blood leukocytes.
      The regions containing the NcoI polymorphic site at position +252 of TNFbeta
      gene, the RsaI polymorphic site at position -592 of IL-10 gene, and the AvaI
      polymorphic site at position -511 of IL-1beta gene were amplified by polymerase
      chain reaction (PCR) and subsequently digested with NcoI, RsaI, and AvaI
      restriction enzyme, respectively. The polymorphic regions with intron 2 of the IL
      1 ra gene (IL-1 RN) containing variable numbers of a tandem repeat of 86 base
      pairs, were amplified by PCR. RESULTS: Univariate analysis showed that recipient
      IL-10, IL-1beta, and IL-1 RN polymorphisms were not associated with the presence
      of pneumonia (P = .589, .940, and .286, respectively). However, compared with GG
      genotype, recipient TNFbeta +252AA + AG genotype was significantly associated
      with susceptibility to pneumonia (P = .006). Age of 45 years or older was not
      significantly associated with susceptibility to develop pneumonia but had a
      tendency to develop it (P = .119). After adjusting for age of 45 years or older,
      recipient TNFbeta+252 AA + AG genotype (odds ratio = 5.366, 95% confidence
      intervals = 1.470 - 19.589, P = .011) independently predicted the risk for
      pneumonia within the first year after kidney transplantation in the multivariate
      analysis. CONCLUSION: These results suggested that recipient TNFbeta gene
      polymorphism may be useful in predicting pneumonia, hence identifying individuals
      who could benefit from preventive treatment and a less potent immunosuppression
      regimen.

PMID- 23953531
TI  - Candida species contamination of preservation fluid-outcome of renal
      transplantation in 6 patients.
AB  - BACKGROUND: Fungal infections are a rare but important cause of morbidity and
      mortality in kidney transplantation. Fungal contamination of the kidney
      preservation fluid may, sometimes, be the cause of these infections. However, the
      clinical consequences of fungal contamination of this fluid are not completely
      understood and literature on this topic is controversial. The purpose of this
      study was to determine the incidence of preservation fluid contamination by fungi
      and its clinical consequences. METHODS: From June 2010 to September 2011, a
      prospective cohort analysis was conducted at our center, enrolling all patients
      who received a renal allograft and whose perfusion fluid was analyzed for
      microbiology sterility. Patients with perfusion fluids positive for fungi were
      further studied: the patients' status was assessed during regular visits and data
      were recorded, including clinical characteristics, infections, graft function,
      immunosuppressive regimen and outcomes. RESULTS: Microbiologic, cultures of 70
      kidney perfusion fluids using specific mycologic media, obtained from 74
      cadaveric renal transplants (4 fluids were unsuitable for analysis), were
      evaluated. Six samples were positive for yeasts (8.6%), with 4 isolates of
      Candida albicans and 2 isolates of Candida glabrata. Four patients had no
      evidence of fungal infection during the follow-up period (median 321 days);
      conversely, 2 patients developed severe mycotic vascular complications leading to
      transplantectomy. CONCLUSIONS: Perfusion fluid contamination by fungi is an
      elusive situation that can lead either to an unremarkable clinical course or to
      graft loss life-threatening situations. Routine culture of kidney perfusion fluid
      is critical for prompt diagnosis and early implementation of appropriate
      treatment.

PMID- 23953532
TI  - Transplantation is a risk factor for acute kidney injury in patients undergoing
      total hip replacement arthroplasty for avascular necrosis: an observational
      study.
AB  - BACKGROUND: The increased number of patients undergoing transplantation has
      increased the number of transplant recipients undergoing total hip replacement
      arthroplasty (THRA). We have evaluated the association between transplantation
      and acute kidney injury (AKI) in patients undergoing THRA. METHODS: Patients who
      underwent THRA from May 2004 to February 2012 were retrospectively assessed.
      Their demographic and clinical characteristics, the results of perioperative
      laboratory tests, the amounts of fluids transfused during surgery, and anesthesia
      time were evaluated. Patients were divided into 2 groups: transplant (n = 222)
      and nontransplant (n = 2,044) patients. With use of the maximal Acute Kidney
      Injury Network criteria, AKI was evaluated by changes in creatinine concentration
      within 48 hours of THRA. Propensity analyses and logistic regression were
      performed to evaluate the association between transplantation and postoperative
      AKI. RESULTS: Postoperative AKI was significantly associated with transplantation
      (P < .0001), and transplantation was an independent factor predictive of
      postoperative AKI (P < .0001). CONCLUSIONS: Transplant recipients are at risk for
      AKI following THRA. The mechanism by which organ transplantation enhances
      postoperative AKI warrants further evaluation.

PMID- 23953533
TI  - Late, severe, noninfectious diarrhea after renal transplantation: high-risk
      factors, therapy, and prognosis.
AB  - OBJECTIVE: Late severe noninfectious diarrhea in renal transplant recipients can
      lead to malnutrition and even graft loss. The purpose of this study was to
      evaluate risk factors associated with this condition and summarize therapy for
      these patients. METHODS: For more than 36 months we observed a cohort of 541
      recipients who underwent kidney transplantation from January 2001 to June 2007.
      They were provided a calcineurin inhibitor (CNI) combined with mycophenolate
      mofetil (MMF). The four group includes a continuous cyclosporine (CsA); a
      preconversion to tacrolimus and a postconversion group as well as a continuous
      tacrolimus group. The rate of severe late noninfectious diarrhea was compared
      among the four groups. Risk factors were analyzed between the diarrhea and
      nondiarrhea cohorts. Clinical characteristics, efficacy, and safety were observed
      after modifying the immunosuppressive protocol for late severe noninfectious
      diarrhea recipients. RESULTS: Twenty-eight recipients presented with late sever
      noninfectious diarrhea. No patients displayed chronic diarrhea in the CsA (n =
      145) or preconversion group (n = 95). The rate of diarrhea was 7.31% in the
      postconversion and 7.35% in the tacrolimus group. Using multivariate Cox
      proportional hazards analysis, factors associated with an increased risk of
      noninfectious diarrhea were cytochrome P450(CYP)3A5 *3/*3 type, chronic renal
      allograft dysfunction, and patient ingestion of Tripterygium wilfordii Hook F.
      All diarrheal recipients experienced weight loss, hypoalbuminia, and an increased
      serum creatinine. All affected patients underwent adjustment of the
      immunosuppressive regimen to achieve remission. Renal allograft survival in
      recipients with diarrhea was worse than that in nondiarrheal recipients receiving
      tacrolimus combined with MMF. CONCLUSION: Tacrolimus with MMF increased the risk
      of late severe noninfectious diarrhea among renal transplant recipients compared
      with hosts treats with CsA plus MMF. The CYP3A5 *3/*3 type, chronic renal
      allograft dysfunction, and T. wilfordii supplementation were high-risk factors
      for late diarrhea. Prompt adjustment of immunosuppression was an effective,
      feasible therapy for these patients.

PMID- 23953534
TI  - The impact of ICAM1 and VCAM1 gene polymorphisms on chronic allograft nephropathy
      and transplanted kidney function.
AB  - ICAM-1 and VCAM-1 adhesion molecules play important roles in the immune response
      and emergence of chronic allograft nephropathy (CAN). The several polymorphisms
      of ICAM1 and VCAM1 genes are associated with changes in molecular expression
      therefore affecting allograft function and immune responses after kidney
      transplantation. The aim of this study was to examine the impact of polymorphisms
      in ICAM1 and VCAM1 genes on biopsy-proven CAN and renal allograft function. The
      270 Caucasian renal transplant recipients (166 men and 104 women) were genotyped
      for the rs5498 ICAM1 and rs1041163 and rs3170794 VCAM1 gene polymorphisms using
      real-time polymerase chain reaction. There was no correlation between
      polymorphisms and CAN. Creatinine concentrations in the first month after
      transplantation differed between the rs5498 ICAM1 genotypes (P = .095), being
      higher for GG carriers (AA + AG vs GG, P =.07) albeit not with statistical
      significance. Creatinine concentrations at 12, 24, and 36 months after
      transplantation differed significantly among rs5498 ICAM1 genotypes (P = .0046, P
      =.016, and P = .02) and were higher among GG carriers (AA + AG vs GG, P = .001, P
      = .004, and P = .006). Rs5498 ICAM1 GG genotype and receipient male gender were
      independent factors associated with higher creatinine concentrations. These
      results suggest that the rs5498 ICAM1 GG genotype may be associated with long
      term allograft function. 

PMID- 23953535
TI  - Difference in outcomes between living left lobe donors and noncirrhotic subjects
      undergoing left lobe resections.
AB  - OBJECTIVES: The aim of this study was to compare short- and long-term outcomes
      between the living donors and patients without cirrhosis after left lobe
      resection. MATERIAL AND METHODS: We retrospectively collected data from 40 left
      lobe donors (Group 1) and from 40 patients who had undergone left liver resection
      for various diseases (Group 2) from 2002 to 2010. In addition to preoperative
      parameters, we compared intraoperative variables as well as, short- and long-term
      outcomes, including postoperative complications and laboratory test results. The
      liver functions included total bilurubin (TB), aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), international normalized ratio (INR), and albumin
      (ALB) compared as well as changes in white blood cell (WBC) count and platelet
      count. RESULTS: The preoperative parameters of the two groups were comparable.
      There was significantly more blood loss in Group 2 than Group 1 (422.5 mL vs
      318.8 mL; P = .001), leading to more autologous blood transfusions in Group 2 (P
      = .008). The other intraoperative variables were similar between the two groups.
      The overall postoperative complication rate was similar: 4% in Group 1 and 8% in
      Group 2 (P = .213); however, there were longer hospital stays and overall costs
      in Group 1 (P < .05). The total bilirubin level, AST, and ALT of Group 2 were
      worse than those in Group 1 during the early postoperative period. Upon long-term
      follow-up the postoperative platelet count decreased in the two groups compared
      with the preoperative levels. CONCLUSION: The type and rate of complications
      following left hepatectomy were similar between donors and noncirrhotic hepatic
      patients. Nevertheless, more serious liver dysfunction postoperatively was
      observed among the patient group.

PMID- 23953536
TI  - Intraoperative "no go" donor hepatectomy in living donor liver transplantation.
AB  - BACKGROUND AND OBJECTIVE: Although there are many reports on donor safety, there
      are few concerning aborted donations. We sought to analyze the "no go" donor
      hepatectomies in our liver transplantation center over 10 years' experience.
      METHODS: Among 290 living donors brought to the operating room for liver graft
      harvest from March 2002 to April 2012, we examined the reasons to abandon the
      procedure, comparing their data with those of successful donors. RESULTS: The
      donor operation was aborted in 5 cases various for reasons. The main reason for
      the abandonment of the operation process was poor liver quality: in single cases
      there was: poor liver quality due to a massive cirrhotic nodule observed by
      laparoscopy; serious steatosis of the liver, indicated by an intraoperative
      biopsy; and an unsuitable biliary anatomy, including 4 branches with 2 small
      ones. In another case, a biliary duct variation in the intraoperative
      cholangiogram showed a narrow crotch of the left and right ducts. In the 5th
      case, the donor would have been left with only a small remaining left lobe (<30%)
      if the right lobe had been harvested. All 5 donors proceeded to accept a right
      lobe hepatectomy. Comparison with the 285 successful donors showed no significant
      differences in preoperative demographic data. All 5 donors recovered without
      complication and were in good condition over long-term follow-up. CONCLUSIONS: A
      low rate of "no go" donor hepatectomy can be achieved. There was no short- or
      long-term harm to the living donor owing to abandonment of the procedure.

PMID- 23953537
TI  - Intraoperative fluid and pharmacologic management and the anesthesiologist's
      supervisory role for nontraditional technologies during liver transplantation: a
      survey of US academic centers.
AB  - BACKGROUND: Volume resuscitation and use of vasoactive medications during liver
      transplantation has not been systematically assessed. Furthermore, the
      anesthesiologist's role for intraoperative oversight of technologies such as
      renal replacement therapy and procedures such as venovenous bypass is poorly
      defined, and it is unclear if the center's annual transplant frequency affects
      these practices. METHODS: We conducted a database analysis of the Liver
      Transplant Anesthesia Consortium survey 202 that addresses these questions. Data
      from US academic liver transplant anesthesia programs meeting inclusion criteria
      were included. Results were categorized by their annual transplant volume.
      RESULTS: A representative sample of 66% of all eligible centers contributed to
      the results. Normal saline among crystalloids and albumin among colloids were the
      most frequently chosen maintenance and non-blood product volume expansion fluids,
      with little variation by center size. A large variety of vasoactive agents is
      routinely utilized across programs, with vasopressors as a cornerstone of
      hemodynamic support. Large programs seem to use less of these agents compared
      with lower volume centers. CONCLUSION: Anesthesiologists are increasingly
      involved in oversight and management of intraoperative renal replacement
      therapies, venovenous bypass and cell saver devices with rising transplant
      frequency. This new insight may be indicative of skill sets needed by members of
      liver transplantation anesthesia teams and should be considered in curriculum
      design for hepatobiliary transplant anesthesia fellowships.

PMID- 23953538
TI  - Roux-en-Y choledochojejunostomy versus duct-to-duct biliary anastomosis in liver
      transplantation for primary sclerosing cholangitis: a meta-analysis.
AB  - BACKGROUND: Roux-en-Y choledochojejunostomy and duct-to-duct anastomosis are
      potential methods for biliary reconstruction in liver transplantation (LT) for
      recipients with primary sclerosing cholangitis (PSC). However, there is
      controversy over which method yields superior outcomes. The purpose of this study
      was to evaluate the outcomes of duct-to-duct versus Roux-en-Y biliary anastomosis
      in patients undergoing LT for PSC. METHODS: Studies comparing Roux-en-Y versus
      duct-to-duct anastomosis during LT for PSC were identified based on systematic
      searches of 9 electronic databases and multiple sources of gray literature.
      RESULTS: The search identified 496 citations, including 7 retrospective series,
      and 692 patients met eligibility criteria. The use of duct-to-duct anastomosis
      was not associated with a significant difference in clinical outcomes, including
      1-year recipient survival rates (odds ratio [OR], 1.02; 95% confidence interval
      [CI], 0.65-1.60; P = .95), 1-year graft survival rates (OR, 1.11; 95% CI, 0.72
      1.71; P = .64), risk of biliary leaks (OR, 1.23; 95% CI, 0.59-2.59; P = .33),
      risk of biliary strictures (OR, 1.99; 95% CI, 0.98-4.06; P = .06), or rate of
      recurrence of PSC (OR, 0.94; 95% CI, 0.19-4.78; P = .94). CONCLUSIONS: There were
      no significant differences in 1-year recipient survival, 1-year graft survival,
      risk of biliary complications, and PSC recurrence between Roux-en-Y and duct-to
      duct biliary anastomosis in LT for PSC.

PMID- 23953539
TI  - Physicochemical evaluation of acid-base disorders after liver transplantation and
      the contribution from administered fluids.
AB  - OBJECTIVES: To analyze the mechanism of acid-base disorders in liver transplant
      recipients and to examine the relationship between these disorders and the fluids
      administered during surgery. METHODS: This prospective study in a university
      affiliated hospital intensive care unit (ICU) included 52 patients admitted to
      the ICU from December 2009 to January 2011. We examined the contributions of
      inorganic ion differences, lactate, unmeasured anions, phosphate, and albumin to
      metabolic acidosis. In addition to laboratory variables, we collected demographic
      and clinical data. RESULTS: Metabolic acidosis (standard base excess <= -2.0
      mmol/L) was identified in 37 (71.2%) patients during the immediate postoperative
      period. The inorganic ion difference was the main determinant of acidosis,
      accounting for -6.17 mEq/L of acidifying effect. The acidemia was attenuated
      mainly by the alkalinizing effect of albumin reduction, which contributed +6.03
      mEq/L. There was an inverse proportional relationship between the quantity of
      saline solution used during surgery and the inorganic ion difference during the
      immediate postoperative period. CONCLUSIONS: Hyperchloremia is the primary
      contributor to metabolic acidosis in liver transplant recipients. Possibly the
      use of chloride-rich solutions increases the incidence of this disorder.

PMID- 23953540
TI  - The impact of obesity as determined by modified body mass index on long-term
      outcome after liver transplantation: Canadian single-center experience.
AB  - BACKGROUND: Obesity is thought to be associated with higher rates of morbidity
      and mortality after liver transplantation (LT); however, its actual impact is
      difficult to evaluate, in part because of the confounding effects of fluid
      accumulation on body mass index (BMI). OBJECTIVE: We sought to define the effects
      of conventional BMI (cBMI) and modified BMI (mBMI; calculated by multiplying the
      BMI by serum albumin level to compensate for fluid accumulation), on the outcome
      of LT recipients overall. METHODS: A cohort of 507 patients who underwent LT from
      April 2000 to August 2006 were analyzed. RESULTS: Pre-LT diabetes mellitus was
      seen somewhat more frequently in the higher mBMI group (P = .054), whereas there
      was no difference across cBMI categories. The recipients at extremes of cBMI (>40
      kg/m(2) and <18.5 kg/m(2)) had significantly lower patient and graft survival
      than other groups (P = .038 and P = .010, respectively); however, no
      statistically significant differences were found in overall patient and graft
      survival across mBMI categories. There were no differences in duration of
      intensive care unit stay, duration of overall hospital stay, and vascular
      complications after LT among mBMI categories. CONCLUSIONS: Pre-LT obesity alone,
      when estimated by mBMI rather than by cBMI, should not be a contraindication for
      LT.

PMID- 23953541
TI  - APACHE III score is superior to King's College Hospital criteria, MELD score and
      APACHE II score to predict outcomes after liver transplantation for acute liver
      failure.
AB  - OBJECTIVES: The Model for End-Stage Liver Disease score and King's College
      Hospital (KCH) criteria are accepted prognostic models acute liver failure (ALF),
      while the use of (APACHE) scores predict to outcomes of emergency liver
      transplantation is rare. MATERIALS AND METHODS: The present study included 87
      patients with ALF who underwent liver transplantation. We calculated (KCH)
      criteria, as well as MELD, APACHE II, and APACHE III scores at the listing date
      for comparison with 3-month outcomes. RESULTS: According to the Youden-Index, the
      best cut-off value for the APACHE II score was 8.5 with 100% sensitivity, 49%
      specificity, 24% positive predictive value (PPV), and 100% negative predictive
      value (NPV). Patients with <8.5 points had a significantly higher survival rate
      (P < .05). The proposed APACHE III cut-off was 80. The APACHE III score
      demonstrated the highest specificity and PPV (90% specificity, 50% PPV). The NPV
      was 92%. With a 90-point threshold the specificity increased to 98% with 75% PPV
      and 89% NPV. Only 1 of 4 patients with a score >90 survived transplantation (P =
      .001). MELD score and KCH criteria were not significant (P > .05). According to
      the Hosmer-Lemeshow test, only the APACHE III score adequately describe the data.
      CONCLUSIONS: The APACHE III score was superior to KCH criteria, MELD score, and
      APACHE II score to predict outcomes after transplantation for ALF. It is a
      valuable parameter for pretransplantation patient selection.

PMID- 23953542
TI  - Liver transplantation in patients with atrial fibrillation.
AB  - In this study we described survival and incidence of perioperative and
      postoperative complications in liver transplant recipients with known atrial
      fibrillation. A total number of 717 patients underwent liver transplantation
      between January 2005 and December 2008 at our institution. In this population,
      preoperative paroxysmal or chronic-persistent atrial fibrillation was diagnosed
      in 32 patients (4.5%). Of these, 12 patients died during follow-up and 4 patients
      required liver retransplantation. Perioperative cardiac complications occurred in
      10 patients (31%) resulting in 3 cardiac-related deaths. Median patient survival
      was 1613 days (range, 22-2492) and median graft survival was 1524 days (range, 10
      2492). Twenty patients are still alive with a median survival of 1861 days
      (range, 1189-2492) after liver transplantation. 

PMID- 23953543
TI  - Tacrolimus effects and side effects after liver transplantation: is there a
      difference between immediate and extended release?
AB  - BACKGROUND: Immunosuppressive therapy after orthotopic liver transplantation
      (OLT) requires a high degree of patient compliance to guarantee safety and avoid
      side effects. In 2007, prolonged-release tacrolimus was launched in Europe to
      improve compliance. In this prospective observational crossover single-center
      trial, we analyzed effects and side effects of prolonged-release tacrolimus in
      OLT patients. METHODS: LT patients at our center were included if they were older
      than l8 years of age, had had the procedure at least 6 months prior, and were
      outpatients currently on twice-daily tacrolimus. Patients were observed for 6
      months before switching to once-daily tacrolimus. Patient history, clinical
      examination, and laboratory examinations were recorded on inclusion as well as
      after 3, 6, 9, 12, and 18 months. RESULTS: The rates of rejection, hypertension,
      hypercholesterolemia, and diabetes mellitus were compared during twice-daily and
      once-daily tacrolimus. Similarly, laboratory parameters were identical during
      both periods with the exception of glycated hemoglobin, which was significantly
      elevated under once-daily tacrolimus (P = .00l). CONCLUSION: Converting patients
      to extended-release tacrolimus with was safe in terms of rejection, hypertension,
      and hypercholesterolemia as well as renal and liver functions. Further
      investigations concerning pharmacokinetics and glucose metabolism will be needed
      to evaluate prolonged-release tacrolimus.

PMID- 23953544
TI  - Hepatitis B prophylaxis using lamivudine and individualized low-dose hepatitis B
      immunoglobulin in living donor liver transplantation.
AB  - BACKGROUND: Currently, most available experience concerning prophylaxis against
      hepatitis B virus (HBV) recurrence after living donor liver transplantation
      (LDLT) is limited to studies of small size and short follow-up. The objective of
      this study was to evaluate the efficacy of a prophylactic regimen using
      lamivudine and individualized low-dose intramuscular hepatitis B immunoglobulin
      (HBIG) in LDLT. METHODS: We used a database of adult-to-adult right-lobe LDLT
      procedures performed from June 2002 to April 2012 at our center for HBV-related
      end-stage liver diseases. Patients were divided into 3 groups: group A, HBV
      related decompensated liver cirrhosis; group B, fulminant hepatitis B; and group
      C, hepatocellular carcinoma (HCC). RESULTS: During a mean follow-up of 38.3 +/-
      28.9 months, 8 of 165 (4.8%) recipients developed HBV recurrences. The mean time
      for HBV reinfection was 15.8 + 11.0 months after transplantation. The overall 1-,
      3-, and 5-year HBV recurrence rates were 3%, 7%, and 8.2%, respectively. Both
      patients with fulminant hepatitis B or HCC seemed to have higher rates of HBV
      recurrence than those with decompensated liver cirrhosis, albeit not
      significantly. The independent predictor of HBV recurrence was high HBV DNA level
      (>=10(5) copies/mL) at LDLT. CONCLUSIONS: Lamivudine and individualized low-dose
      intramuscular HBIG provides effective prophylaxis against HBV recurrence after
      LDLT. Pre-LDLT HBV DNA of >= 10(5) copies/mL was associated with HBV recurrence.

PMID- 23953545
TI  - Angiotensin blockade does not affect fibrosis progression in recurrent hepatitis
      C after liver transplantation.
AB  - BACKGROUND: Liver transplantation (LT) for hepatitis C virus (HCV)-related end
      stage liver disease is impaired by universal disease recurrence and suboptimal
      response to antiviral therapy. Inhibition of angiotensin-II signalling by
      angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin-II receptor
      blockers (ARB) decreases hepatic stellate cell activation in vitro and hepatic
      fibrogenesis in animal models. A single-center retrospective analysis suggested
      that angiotensin blockade (AB) inhibits fibrosis progression in recurrent HCV
      post-LT. This study assessed the effect of AB on fibrosis progression in an
      independent patient cohort. METHODS: Chart review of all patients who underwent
      transplantation in our institution for HCV-related ESLD between January 2000 and
      February 2008 revealed 109 patients with >=2 protocol liver biopsies and free of
      antiviral therapy post-LT up to the last biopsy analyzed; 27 of 109 patients were
      treated with ACE-I/ARB for >=12 months, 82 were not. Fibrosis was staged using
      METAVIR. RESULTS: Live-donor LT was more frequent in controls than in the AB
      group (25% vs 11%; P < .05). However, parameters known to affect outcome of
      recurrent HCV, including donor age, prevalence of diabetes, acute cellular
      rejection, and immunosuppression, were similar in both groups. Time between first
      and last biopsy (median, 23 months), stage of fibrosis, fibrosis progression
      rates (median 0.47 vs 0.45 unit/y; P = .46), and time to develop fibrosis stage
      >=2 did not differ between groups. Results held true if deceased-donor LT were
      analyzed separately. CONCLUSION: Our study does not support the contention of a
      previous report that use of AB reduces fibrosis progression in recurrent HCV post
      LT.

PMID- 23953546
TI  - Association between serum C-reactive protein and albumin levels and psychiatric
      comorbidities in liver transplant recipients.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is the definitive treatment
      for patients with end-stage liver disease. Many post-OLT patients have
      psychiatric comorbidities. The relationship between psychiatric comorbidities and
      biological factors, such as C-reactive protein (CRP) and albumin levels, in OLT
      recipients has seldom been investigated. METHODS: We analyzed medical charts of
      all patients aged over 18 who underwent orthotopic OLT at a tertiary medical
      center between September 2008 and July 2010 for serum CRP and albumin levels
      before and 1 month after OLT. Data for baseline characteristics, such as gender,
      age, and body mass index (BMI), were also collected. Patients who had a
      psychiatric consultation or took psychotropic medications during the
      hospitalization were categorized as "with psychiatric comorbidities." RESULTS:
      Psychiatric comorbidities existed in 51 (33.8%) of 151 OLT recipients. By
      analysis of covariance adjusted for age and BMI, post-OLT CRP levels in patients
      with psychiatric comorbidities were significantly higher than those without
      psychiatric comorbidities (P = .015). For patients with psychiatric
      comorbidities, the paired t test showed significantly increased CRP levels at 1
      month after when compared to the pre-OLT baseline levels (P = .044). Patients
      without psychiatric comorbidities had significantly decreased CRP levels at 1
      month after when compared with the pre-OLT baseline levels (P = .009).
      CONCLUSIONS: Elevated CRP levels may indicate activation of a systemic
      inflammatory process caused by psychiatric comorbidities in OLT recipients.

PMID- 23953547
TI  - Diagnostic value of magnetic resonance cholangiopancreatography for biliary
      complications in orthotopic liver transplantation: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Magnetic resonance cholangiopancreatography (MRCP) is a
      noninvasive procedure to diagnose biliary complications. The aim of the present
      meta-analysis was to establish the overall diagnostic accuracy of MRCP to
      diagnose biliary complications post-orthotopic liver transplantation (OLT).
      METHODS: A systematic review was performed by searching electronic bibliographic
      databases prior to May 2012. Sensitivity, specificity, and other measures of the
      accuracy of MRCP for diagnosis of post-OLT were summarized using a random-effects
      or a fixed-effects model. Receiver operating characteristic curves were used to
      summarize overall test performance. RESULTS: Fourteen studies, which involved 892
      subjects were eligible for the analysis. The summary estimates of sensitivity,
      specificity, positive likelihood ratio, negative likelihood ratio, diagnostic
      odds ratio, and area under cure of MRCP for diagnosis of biliary complications
      were as follows: 0.95, 0.92, 10.23, 0.08, 206.59, and 0.979, respectively. The
      results for biliary strictures in four studies involving 177 subjects were 0.94,
      0.95, 0.96, 0.09, 178.33, and 0.973 respectively. CONCLUSIONS: MRCP is a
      sensitive and specific technique to diagnose biliary complications.

PMID- 23953548
TI  - Inhaled iloprost plus oral sildenafil in patients with severe pulmonary arterial
      hypertension delays the need for lung transplantation.
AB  - BACKGROUND: Accepted treatment for severe pulmonary arterial hypertension (PAH)
      includes intravenous epoprostenol and lung transplantation (LT). Inhaled iloprost
      plus oral sildenafil (Ilo-Sil) is an alternative strategy that may also delay the
      need for LT. PATIENTS AND METHODS: This was a long-term descriptive study in
      eight patients with PAH functional class (FC) IV with right heart failure, four
      of them potential candidates for LT, who were treated with Ilo-Sil as an
      alternative to epoprostenol. RESULTS: At the start of the study, patients (seven
      women; mean age, 43.8 [range, 34-66] years) were in FC IV and unable to perform
      the 6-minute walk test. Mean cardiac index was 1.9 (range, 1.4-2.1) L/min/m(2).
      Treatment with Ilo-Sil provoked a rapid and sustained improvement; mean walking
      distance at 3 months was 322 +/- 90 m and no patient remained in FC IV. Survival
      at 1 and 5 years was 100% and 75%, respectively. Of the four potential LT
      candidates, one underwent transplantation after 6.8 years and one died after 1.2
      years. CONCLUSIONS: These results suggest that therapy with Ilo-Sil represents an
      acceptable alternative in patients with severe and unstable PAH.

PMID- 23953549
TI  - Analysis of patients referred to a lung transplantation unit.
AB  - This cross-sectional, concurrent and descriptive study presents the decisions
      regarding patients referred to our Lung Transplantation Unit (LTxU). Each patient
      is discussed in a multidisciplinary clinical session (phase I), rejecting some
      and accepting others for assessment in our LTxU (phase II) according to criteria
      of the National and International Guidelines for Transplantation. A protocol
      assessment in phase II, leads to a decision to reject, accept, or follow-up the
      candidate for LTx. Among 214 evaluation requests received in our unit from May
      2008 to December 2011, 37 patients (17%) were rejected based on the information
      sent to our LTxU. Among the patients evaluated in phase II, 62 (28.9%) were put
      on the waiting list, 125 (58.4%) were rejected, and twenty-seven (12.6%) were
      postponed for future reconsideration, results that were similar to those
      described in the literature. The main disease referred for LTx was obstructive
      airflow (n = 98; 45.7%), followed by interstitial lung disease (ILD; n = 66;
      30.8%), cystic fibrosis or bronchiectasis (n = 20; 9.3%), or primary pulmonary
      hypertension group 1 (n = 20; 9.3%). Ten patients (4.6%) were diagnosed with
      other respiratory diseases. Most patients (n = 165; 77.1%) lived in the region of
      our hospital (Madrid). The main reasons to reject patients for LTx were
      malnutrition, severe disease in other organs, toxic habits, and refusal of
      treatment. Finally, one out of four referred patients was accepted for LTx. In
      addition to serious comorbidities in various organs, a high percentage of
      patients who were not accepted for LTx because of these factors might have been
      of accepted had these conditions been corrected before patient referral. 

PMID- 23953550
TI  - Outcome of TiNi stent treatments in symptomatic central airway stenoses caused by
      Aspergillus fumigatus infections after lung transplantation.
AB  - BACKGROUND: Central airway stenoses due to Aspergillus fumigatus infections have
      been a significant cause of morbidity and mortality after lung transplantation.
      We reviewed our experience using self-expandable braided TiNi-metallic stents in
      the management of 4 single-lung transplant recipients with central airways
      stenoses between January 2003 and June 2010. METHODS: Thirty-six single-lung
      transplant recipients were subjected to pulmonary function testing and
      surveillance bronchoscopy with biopsy at predetermined intervals and when
      clinically indicated. Bronchial wash fluid and biopsy material were examined by
      appropriate fungal stain and culture techniques. RESULTS: Nine of 36 patients
      (25%) were diagnosed with Aspergillus fumigatus infections; 4 (11.1%) showed
      rapid decrease in pulmonary function and developed severe upper airway narrowings
      with about 80% of the central airway obstructed by thick plugs of mucus, heavily
      laden with Aspergillus species. All 4 patients were managed with stent placement
      as well as antifungal treatments and showed a forced vital capacity and forced
      expiratory volume in 1 second improvement of 11.3% and 25.9%, respectively after
      1 month. CONCLUSIONS: TiNi stent applications in combination with antifungal
      drugs are sufficient to treat central airway stenoses after lung transplantation.

PMID- 23953551
TI  - Use of ventricular assist device as bridge to simultaneous heart and kidney
      transplantation in patients with cardiac and renal failure.
AB  - BACKGROUND: Ventricular assist device (VAD) implantation as a bridge to cardiac
      transplantation is an effective treatment option for end-stage heart failure.
      Renal dysfunction is not uncommon but is considered to be a poor prognostic
      factor. We present our experience with 6 patients who had combined heart and
      kidney transplantation (HKT) after VAD implantation for advanced cardiac and
      renal failure. METHODS: Of 74 patients who underwent VAD implantation as a bridge
      to transplant from May 2001 to September 2009, 28 patients developed renal
      failure, and of these, 6 (5 male, 1 female, ages 40-64 years) had HKT. All
      required hemodialysis because of renal failure before HKT. Immunosuppression
      consisted of anti-thymocyte globulin followed by triple drug therapy consisting
      of calcineurin inhibitors, mycophenolate, and corticosteroids. RESULTS: Of the 6
      HKT patients, 5 (83%) were alive without hemodialysis at 1 and 2 years; of the 22
      patients with renal failure after VAD implantation without subsequent transplant,
      1- and 2-year survivals were zero. Interval from VAD implantation to HKT ranged
      from 36 to 366 days (133 +/- 127 days). At 6 months after HKT (100% alive), left
      ventricular ejection fraction was 60.2 +/- 5.8% and serum creatinine 1.1 +/- 0.2
      mg/dL. Three HKT patients required temporary hemodialysis after surgery.
      Endomyocardial biopsy showed absence of ISHLT grade 2R-3A or greater cellular
      rejection, and none showed evidence of definite antibody-mediated rejection.
      CONCLUSIONS: Based on our initial experience, simultaneous HKT is a safe
      treatment option with excellent outcomes for patients with advanced heart failure
      and persistent renal dysfunction after VAD implantation.

PMID- 23953552
TI  - Heart transplantation for end-stage heart failure due to cardiac sarcoidosis.
AB  - BACKGROUND: Cardiac sarcoidosis with end-stage heart failure has a poor prognosis
      without transplantation. The rates of sarcoid recurrence and rejection are not
      well established after heart transplantation. METHODS: A total of 19 heart
      transplant recipients with sarcoid of the explanted heart were compared with a
      contemporaneous control group of 1,050 heart transplant recipients without
      cardiac sarcoidosis. Assessed outcomes included 1st-year freedom from any treated
      rejection, 5-year actuarial survival, 5-year freedom from cardiac allograft
      vasculopathy (CAV), 5-year freedom from nonfatal major adverse cardiac events (NF
      MACE), and recurrence of sarcoid in the allograft or other organs. Patients with
      sarcoidosis were maintained on low-dose corticosteroids after transplantation.
      RESULTS: There were no significant differences between the sarcoid and control
      groups in 1st-year freedom from any treated rejection (79% and 90%), 5-year
      posttransplantation survival (79% and 83%), 5-year freedom from CAV (68% and
      78%), and 5-year freedom from NF-MACE (90% and 88%). Causes of death (n = 5) in
      the sarcoid group were coccidioidomycosis, pneumonia, rejection, hemorrhage, and
      CAV. No patient had recurrence of sarcoidosis in the cardiac allograft. Three of
      19 patients (16%) experienced recurrence of extracardiac sarcoid, with no
      mortality. CONCLUSIONS: Patients with cardiac sarcoidosis undergoing heart
      transplantation have acceptable long-term outcomes without evidence of recurrence
      of sarcoidosis in the allograft when maintained on low-dose corticosteroids.
      Progression of extracardiac sarcoid was uncommon, possibly related to
      immunosuppression. In patients with cardiac sarcoidosis, heart transplantation is
      a viable treatment modality.

PMID- 23953553
TI  - A 1-year randomized controlled study of everolimus versus mycophenolate mofetil
      with reduced-dose cyclosporine in maintenance heart transplant recipients.
AB  - BACKGROUND: The aim of this study was to demonstrate noninferiority of everolimus
      with reduced cyclosporine (CsA) vs mycophenolate mofetil (MMF) with reduced CsA
      in improving renal function. METHODS: In this 1-year randomized, open-label,
      noninferiority study in maintenance heart transplant recipients with impaired
      renal function 70 patients received everolimus (n = 36) or MMF (n = 34) in
      combination with reduced CsA. The planned sample size was not reached as the
      study was prematurely discontinued due to slow recruitment. RESULTS:
      Noninferiority of the everolimus regimen could not be shown: In the total
      population MMF seemed to be favorable on renal function assessed by serum
      creatinine and filtration rates, but not in the subset of patients who reached
      the intended reduced CsA level. Incidence rates of rejection episodes were
      significantly higher under MMF at month 6 (P = .0332). CONCLUSIONS: Overall, the
      results of this trial using reduced CsA in combination with either everolimus or
      MMF show that there is evidence to reduce the CsA level when everolimus is given
      concomitantly and that the benefit of MMF with reduced CsA levels is limited due
      to insufficient immunosuppression.

PMID- 23953554
TI  - Antithymocyte globulin induction therapy adjusted for immunologic risk after
      heart transplantation.
AB  - INTRODUCTION: The efficacy of antithymocyte globulin (ATG) induction in the
      therapy of immunologically low- and high-risk patients after heart
      transplantation is not known. METHODS: All patients who received ATG induction
      from January 2000 through January 2010 were divided into two groups based on the
      risk of rejection. A higher-risk group (age younger than 60 years, multiparous
      females, African Americans, panel-reactive antibody >10%, or positive cross
      match) received ATG (1.5 mg/kg) for 7 days (ATG7), and the remaining lower-risk
      group received ATG for 5 days (ATG5), all followed by calcineurin inhibitor,
      mycophenolate, and prednisone. Endomyocardial biopsies were performed based a
      standard protocol for up to 3 years after heart transplantation, and for
      suspected rejection. RESULTS: Of 253 heart transplant recipients, 87 received
      ATG5 and 166 ATG7. Absolute lymphocyte count <200 per microliter was achieved
      within 10 days in 88% of ATG5 and 86% of ATG7. Baseline creatinine was 1.3 +/-
      0.8 pre-transplantation, 1.8 +/- 0.9 post-transplantation, and 1.0 +/- 0.4 mg/dL
      at discharge (mean +/- standard deviation [SD]; P < .001, compared with pre
      transplantation). Of 3667 biopsies, 33 (0.90%) had >=3A/2R cellular rejection
      (CR). Of 3599 biopsies, 16 (0.44%) had definite antibody-mediated rejection
      (AMR). At 5 years, freedom from >=3A/2R CR (94% +/- 2.8% vs 83% +/- 7.7%; P =
      .31) and freedom from AMR (95% +/- 2.4% vs 90% +/- 6.4%; P = .98) were similar
      between ATG5 and ATG7, respectively. Survival for ATG5 and ATG7 was comparable at
      one year (94% +/- 2.5% vs 93% +/- 2.0%), and at 8 years (61% +/- 6.9% and 61% +/-
      4.7%; P = .88). At 5 years, ATG5 and ATG7 were similar in freedom from
      cytomegalovirus (CMV) infection (92.3% vs 94.3%; P = not significant [NS]),
      freedom from pneumonia (83.8% vs 82.1%; P = NS), and in rate of malignancy
      (excluding skin cancer; 8.0% vs 6.0%; P = NS). CONCLUSIONS: ATG induction therapy
      (prospectively dose-adjusted for immunologic risk) in low- and high-risk patients
      results in excellent and equivalent short- and long-term survival rates, with a
      low incidence of CR and AMR. The use of ATG does not increase rates of CMV
      infection with appropriate prophylaxis. ATG may benefit renal function by
      delaying calcineurin inhibitor exposure, and may have a role in the prevention of
      AMR.

PMID- 23953555
TI  - Outcomes of adult orthotopic heart transplantation with extended allograft
      ischemic time.
AB  - BACKGROUND: Heart procurement for orthotopic heart transplant (OHT) is limited by
      the conventional 4 hours of ischemic time (IT). Based on a recent report from our
      center showing that extended IT from a young donor group is safe, we widened our
      geographical reach, resulting in almost 40% of our transplants having an IT > 4
      hours. METHODS: We retrospectively reviewed records of adult patients who
      underwent OHT from January 2006 to December 2011. The primary outcome was
      survival, and secondary outcomes included resource utilization, end-organ
      dysfunction, and acute cellular rejection. Overall survival was analyzed using
      Kaplan-Meier curves and log-rank tests. Secondary outcomes were compared with a
      combination of parametric and nonparametric statistics. RESULTS: A total of 323
      patients underwent OHT. There was a significant difference in overall survival
      between the standard and extended IT groups (85.7% vs 76.4%, P = .03). There were
      no significant differences between the groups for secondary outcomes except a
      higher incidence of liver dysfunction in the extended IT group (84.9% vs 73%, P =
      .01). Further analysis revealed that mortality remains similar if IT is below 4
      hours and between 4 and 5 hours, but begins to climb after 5 hours, driving the
      difference between our standard and extended IT. CONCLUSIONS: Limited donor
      availability for OHT dictates alternative strategies to enlarge the donor pool.
      Although there is an overall increasing risk with extended IT beyond 4 hours, it
      may be possible to safely increase the threshold to at least 5 hours without
      compromising the outcomes.

PMID- 23953556
TI  - Granulocyte colony-stimulating factor therapy is associated with a reduced
      incidence of acute rejection episodes or allograft vasculopathy in heart
      transplant recipients.
AB  - BACKGROUND: We evaluated the potential effects of granulocyte colony-simulating
      factor (G- CSF) on the incidence of rejection and allograft vasculopathy in heart
      transplant recipients. METHODS: Of 247 patients undergoing heart transplantation
      from 2000 to 2007, 52 (21%) developed leukopenia (white blood cell [WBC] <2.5 *
      10(9) cells/L) in the absence of active infection, rejection, or malignancy. In
      24 (46%) patients a clinical decision was made to treat the leukopenia with G-CSF
      (G-CSF group), and 28 (54%) Patients received no G-CSF (non-GCSF group). Patients
      followed up for 1 year after the period of leukopenia were assessed for allograft
      vasculopathy and acute rejection incidence. RESULTS: At baseline, the G-CSF group
      and the non-GCSF group did not differ in age, gender, race, heart failure
      etiology, creatinine, left ventricular ejection fraction (LVEF) or
      immunosupressive regimen. During 1-year follow-up there were no deaths in the G
      CSF group, and 1 death in the non-GCSF group (P = .34). The incidence of
      rejection or progressive allograft vasculopathy was lower in the G-CSF group when
      compared with the non-GCSF group (2 [8%] vs 15 [53%]; P < .01). Multivariate
      analysis identified both prior rejection episodes and G-CSF therapy as factors
      associated with the combined end-point of rejection or progressive allograft
      vasculopathy (odds ratio [OR] = 7.89 [1.67-37.2] and OR = 0.09 [0.02-0.52],
      respectively). CONCLUSIONS: G-CSF therapy appears to be associated with a
      decreased incidence of acute rejection episodes or allograft vasculopathy in
      heart transplant recipients, suggesting a potential immunomodulatory effect of G
      CSF.

PMID- 23953557
TI  - Return to work after heart transplantation: the New Zealand experience.
AB  - INTRODUCTION: Return to work and social re-integration following heart
      transplantation is a significant challenge for patients. The aim of this study is
      to provide a snapshot of the current employment status and factors associated
      with return to work in New Zealand recipients over the past decade. METHODS:
      Consecutive surviving patients who underwent heart transplantation in the 10
      years from June 2001 to June 2011, alive in July 2012, were retrospectively
      identified. Details on demographics, employment before and after transplantation
      were obtained and recorded. RESULTS: A total of 87 patients were included, out of
      a total of 111 patients who underwent heart transplantation in the 10 year period
      from June 2001 (24 patients had died prior to July 2012). The median age of the
      study cohort was 52 years (range 15-75 years) and 19 were female. A total of 51
      (58.6%) patients were in paid employment at the time of review. Of the 36 (41.4%)
      patients not in paid employment, 5 were students, 12 were retired and 10 were
      homemakers or not working through lifestyle choice. Two patients were unable to
      work for health reasons. Seven (8%) patients considered able to work were on an
      unemployment or invalid's benefit. Of the patients working prior to heart
      transplantation, 88.9% returned to work after a median of 8.5 months, and 70.6%
      remained on paid employment at a median follow-up of 77 months after
      transplantation. There was a statistically significant correlation between the
      time of stopping work prior to transplant and return to work after transplant (r
      = 0.497, P < .01). CONCLUSION: The current rate of paid employment in patients
      who underwent heart transplantation was similar to the overall employment rate in
      New Zealand. The most important predictor of returning to work was employment
      status prior to transplantation. Discussions regarding return to work early in
      the transplantation assessment process and actively assisting patients to seek
      employment after transplantation may improve employment rates.

PMID- 23953558
TI  - The safe minimally ischemic liver remnant for small-for-size syndrome in porcine
      hepatectomy.
AB  - BACKGROUND: The minimal functional remnant liver mass or graft after an ischemic
      injury in hepatectomy or living donor liver transplantation (LDLT) is not clear.
      This study sought to determine the minimal remnant liver (MRL) size after 20
      minutes hepatic inflow occlusion (HIO) and the maximal portal flow with which the
      liver remnant can sustain in a porcine model. METHODS: Twenty pigs that underwent
      massive hepatectomy were randomly divided into 3 groups: 30% group, the remnant
      constituted about 30% of total liver volume (TLV); 35%+O group, the remnant
      constitute about 35% of TLV with 20 minutes HIO, and 30%+O group, the remnant
      constituted about 30% of TLV with 20 minutes of HIO. We evaluated survival rates,
      kinetic portal vein pressures (PVP), hemodynamics, hepatocyte metabolism, and
      injury. RESULTS: The 14-day survival rate in the 30%+O group was significantly
      reduced compared with that of either the 30% group or the 35%+O group: l00%
      versus 28.6% versus 85.7% respectively (P = .009). The tissue, serum analyses,
      and PVP in the 30%+O group were significantly different compared with the
      measurements among the other groups (P < .05), revealing that the liver remnant
      in 30%+O group could not sustain more than 3 times baseline portal flow, whereas
      in 35%+O group it could sustain 2.8 times baseline portal flow. CONCLUSIONS:
      Intraoperative ischemia can injure the sinusoidal endothelium, decreasing its
      ability to regulate portal hyperperfusion, causing less than 30% to 35% of TLV to
      show small-for-size syndrome or postoperative liver failure.

PMID- 23953559
TI  - Establishment of a simple living donor liver transplantation dog model using a
      two-step nonvenous bypass hepatectomy.
AB  - AIM: Dogs are an ideal model for studying living donor liver transplantation
      (LDLT). However, due to their poor tolerance to congestion and acidosis during
      portal vein blockage, current LDLT dog models with long operation times have high
      mortality. To address the issue, we designed a novel simplified operation with
      two-step nonvenous bypass (NVB) hepatectomy. METHODS: Eighty dogs were evenly
      randomized to the living liver donor (LLD) or the recipient (LLR) groups. A
      standard lobectomy of I, II, and III lobes was performed in the LLD group. In the
      LLR group, first only I, II, and III lobes were resected using NVB; the residual
      lobes were resected off just after donor lobes were implanted. RESULTS: For the
      LLD group, the operation time was 172.67 +/- 20.98 minutes, amount of blood loss
      was 71.39 +/- 13.59 mL, and 2-week survival rate was 85.00%. For the LLR group,
      the operation time was 251.61 +/- 22.87 minutes, amount of blood loss was 220.00
      +/- 96.40 mL, amount of blood transfusion was 163.89 +/- 44.74 mL, and 48-hour
      survival rate was 77.14%. In the LLR group, the mean arterial and central venous
      pressures decreased after organ implantion, but gradually recovered to normal
      levels after surgery. The liver function biochemical parameters recovered to
      preoperational levels after 14 days in the LLD group; in the LLR group, they
      gradually increased during 48 hours after operation. CONCLUSION: The present
      method with two-step NVB hepatectomy can be used efficiently and safely for
      establishing LDLT dog model.

PMID- 23953560
TI  - The effect of octreotide on hepatic ischemia-reperfusion injury in a rabbit
      model.
AB  - BACKGROUND: Hepatic ischemic-reperfusion injury (HIRI) is a major cause of
      morbidity and mortality following liver surgery. Octreotide (Oct) has been
      reported to improve hepatocellular energy metabolism in a rat HIRI model. This
      study was designed to evaluate whether Oct could protect the liver of rabbits
      against ischemic-reperfusion (I/R) injury. METHODS: Twenty-four adult New Zealand
      rabbits were randomly divided into a sham operated group (Control), an
      ischemia/reperfusion group (I/R), and an ischemia/reperfusion + Oct pretreatment
      group (I/R + Oct). The hemodynamic (mean arterial pressure [MAP] and heart rate
      [HR]) changes, liver enzymes (alanine aminotransferase [ALT], aspartate
      aminotransferase [AST], and lactate dehydrogenase [LDH]) release, inflammatory
      cytokines (tumor necrosis factor [TNF]alpha and interleukin [IL]-1beta) levels,
      and endotoxin (ETX) levels were measured during I/R. RESULTS: Compared with the
      Control group, the MAP decreased and HR increased in I/R and I/R + Oct groups at
      ischemia 15 minutes (P < .05) but were less in the I/R + Oct group relative to
      the I/R group (P < .05). ALT, AST, LDH, IL-1beta, and ETX levels were increased
      in the I/R and I/R + Oct groups at ischemia 30 minutes (P < .05), however, the
      increase was lower in the I/R + Oct group relative to the I/R group (P < .05).
      Bcl-2 expression in the I/R + Oct group was higher compared with other groups (P
      < .05) and Bax expression in the I/R group was reduced compared with other groups
      (P < .05). Hepatocellular damage in the I/R + Oct group appeared to be less than
      in the I/R group by microscopy. CONCLUSIONS: Oct pretreatment attenuated
      hemodynamic changes and decreased liver enzyme changes induced by HIRI in a
      rabbit model. The protection mechanisms of Oct may be related to reduced ETX
      levels, down-regulation of the inflammatory cytokines TNFalpha and IL-1beta, and
      inhibition of hepatocellular apoptosis, as well as the modulation of the
      mitochondrion-mediated Bcl-2/Bax apoptosis pathway. Based on our study it appears
      that Oct may be useful in decreasing liver injury after liver surgery and/or
      transplantation and may serve as a promising agent against HIRI.

PMID- 23953562
TI  - Effects of organic apricot on liver regeneration after partial hepatectomy in
      rats.
AB  - BACKGROUND: The present study investigated the effects of (sun-dried organic
      apricot/SDOA) supplementation in chow on liver regeneration after partial
      hepatectomy/(PH) in rats. METHOD: In this study, 28 female rats were randomized
      into four groups. On the 7th day of the study, group 1 underwent laparoscopic
      intervention while a PH was performed on the other three cohorts. On day 28, all
      rats were humanely killed. Blood and liver tissue samples were subjected to
      biochemical determinations, histological examinations, and measurement of tissue
      oxidative stress enzyme activity. RESULTS: Serum levels of alanine transaminase
      (ALT), alkaline phosphatase (ALP), and liver tissue glutathione (GSH) activities
      were affected by PH and/or SDOA consumption (P < .05). Moderately staining cell
      counts in group 4 were significantly different from the other three groups (P <
      .05). However, no significant differences were detected among all groups in
      regard to aspartate aminotransferase (AST) serum levels or liver tissue
      superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) or glutathione
      peroxidase (GSHpx) activities (P < .05). CONCLUSION: The 5% SDOA supplementation
      over a 21-day feeding period showed a beneficial effect on liver regeneration in
      rats, as reflects by Ki-67 finding although there was no change in ALT or ALP or
      in liver tissue GSH activity.

PMID- 23953561
TI  - Ambroxol alleviates hepatic ischemia reperfusion injury by antioxidant and
      antiapoptotic pathways.
AB  - BACKGROUND: Hepatic ischemia/reperfusion (HI/R) injury is a common pathologic
      process caused by many clinical settings, such as liver resection, liver
      transplantation, hypovolemic shock, and trauma. The use of ambroxol, which acts
      as a mucolytic agent, provides antioxidant and anti-inflammatory effects.
      METHODS: A rat model of HI/R was induced by clamping the hepatic artery, the
      hepatoportal vein, and the bile duct with a vascular clamp for 30 minutes
      followed by reperfusion for 6 hours under anesthesia. The sham group underwent
      laparotomy without hepatic ischemia. The ambroxol group was injected into the
      tail vein in the ambroxol group 5 minutes before HI/R at one dose of 20 mg/kg, 80
      mg/kg, or 140 mg/kg. The control group underwent the same procedure as the
      ambroxol group but with administration of physiological saline. Liver injury was
      evaluated by biochemical and histopathological examinations. Alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed in serum
      samples. Superoxide dismutase (SOD), catalase (CAT), malondiadehyde (MDA), and
      glutathione (GSH) were spectrophotometrically measured. Furthermore, caspase-3,
      Bcl-2 and Bax expression as well as the level of c-Jun N-terminal kinases (JNK)
      we estimated activation. RESULTS: Wistar rats that received 20, 80 mg or 140 mg
      of ambroxol displayed reduced HI/R injury compared with controls. Use of ambroxol
      reduced the histologic injury and significantly decreased serum ALT and AST
      levels. In addition, ambroxol enhanced the activity of hepatic tissue SOD and
      CAT, increasing GSH but decreasing MDA tissue contents. In the ambroxol group,
      Bcl-2 expression was increased and Bax and caspase-3 decreased compared with the
      controls. Furthermore, ambroxol reduced levels of phosphorylated JNK (P < .05).
      CONCLUSION: These results indicated that ambroxol attenuated rat HI/R through
      upregulation of intracellular antioxidant and anti-apoptotic signaling pathways.

PMID- 23953563
TI  - A novel mechanism of anti-T-lymphocyte globulin mediated by fractalkine in renal
      ischemia-reperfusion injury in rats.
AB  - BACKGROUND: Ischemia-reperfusion injury (IRI) is among the main challenges in
      kidney transplantation. It causes delayed graft function and graft loss in long
      term follow-up studies. Anti-T lymphocyte globulin (ATG), a common induction
      immunosuppressive, has been used in kidney transplantation to prevent rejection.
      Fractalkine (FKN) is among the main chemokines involved in IRI. This study was
      designed to identify the relationship between ATG and FKN after warm ischemia in
      rat kidneys. METHODS: Rats were divided into three groups: Control, IRI+normal
      saline(NS) and IRI+ATG. After IRI was initiated, rats received a dose of ATG or
      NS during surgery as well as two more doses at 24 and 48 hours after surgery. All
      rats were humanely killed at 72 hours. RESULTS: The concentration of FKN as well
      as dendritic cells (DC) and macrophages were lower in both peripheral blood and
      the injured kidney among ATG-treated versus control rats. Additionally cell
      necrosis, cytoplasmic vacuolization, cast formation, and tubular dilatation were
      improved among ATG-treated rats. Serum creatinine levels were lower in rats that
      received ATG. CONCLUSION: ATG depleted the concentration of FKN, which inhibits
      migrations of DCs and macrophages into the kidney, and reduces IRI-related
      pathology.

PMID- 23953564
TI  - Effect of cell permeable peptide of c-Jun NH2-terminal kinase inhibitor on the
      attenuation of renal ischemia-reperfusion injury in pigs.
AB  - The outcomes of organ transplantation have improved due to better
      immunosuppressive drugs, surgical techniques, and management of complications.
      However, ischemia-reperfusion injury remains a challenge affecting graft
      survival. In this study, we employed injection of a protein transduction domain
      (PTD) to inhibit the c-Jun NH2-terminal kinase (JNK) pathway thereby attenuating
      ischemia-reperfusion injury in a porcine model. The PTD-JNK inhibitor (JNKI) was
      administered into the renal artery, allowing it to be taken into various elements
      including vascular endothelial cells by endocytosis via the PTD. Serum creatinine
      and blood urea nitrogen concentrations were lower among PTD-JNKI than controls.
      In addition, renal tissue blood flow was maintained in the PTD-JNKI group,
      resulting in less tissue injury and fewer apoptotic cells. These results
      suggested that the PTD technique improved renal transplantation outcomes. 

PMID- 23953565
TI  - Urinary apolipoprotein M could be used as a biomarker of acute renal injury: an
      ischemia-reperfusion injury model of kidney in rat.
AB  - BACKGROUND: It has been well documented that apolipoprotein M (apoM) is
      principally expressed in hepatocytes as well as renal tubular epithelial cells.
      The importance of apoM in the kidney is unknown. In the present study we examined
      urinary any apoM after short-term ischemia-reperfusion injury (IRI) of kidney in
      a rat model. METHODS: The kidneys of 11 male Sprague-Dawley rats were rendered
      ischemic for 45 minutes followed by different intervals of reperfusion. Serum and
      urine apoM concentrations were determined using a dot-blot analysis with specific
      rabbit anti-human apoM antibodies that cross-react with rat apoM. Serum
      concentrations of blood urea nitrogen (BUN) and creatinine (Cr) were determined
      using standard clinical automated analyses. RESULTS: BUN was significantly
      elevated after 45 minutes of ischemia followed by 24 hours of reperfusion; serum
      Cr concentrations were also significantly increased at 6 and 24 hours of
      reperfusion. Interestingly, similar to BUN and Cr, serum apoM concentrations were
      significantly increased after ischemia for 45 minutes alone and after 2 hours of
      reperfusion. Urinary apoM concentrations were obviously increased after 2 h as
      well as 6 hours of reperfusion. CONCLUSION: apoM showed characteristics of an
      acute-phase reactive protein; its occurrence in urine may be considered to be a
      biomarker of acute renal injury.

PMID- 23953566
TI  - Ischemic preconditioning and tacrolimus pretreatment as strategies to attenuate
      intestinal ischemia-reperfusion injury in mice.
AB  - The intestine is highly sensitive to ischemia-reperfusion injury (IRI), a
      phenomenon occurring in different intestinal diseases. Several strategies to
      mitigate IRI are in experimental stages; unfortunately, no consensus has been
      reached about the most appropriate one. We report a protocol to study ischemic
      preconditioning (IPC) evaluation in mice and to combine IPC and tacrolimus (TAC)
      pretreatment in a warm ischemia model. Mice were divided into treated (IPC, TAC,
      and IPC + TAC) and untreated groups before intestinal ischemia. IPC, TAC, and IPC
      + TAC groups were able to decrease postreperfusion nitrites levels (P < .05). IPC
      containing groups had a major beneficial effect by preserving the integrity of
      the intestinal histology (P < .05) and improving animal survival (P < .002)
      compared with TAC alone or the untreated group. The IPC + TAC group was the only
      one that showed significant improvement in lung histological analysis (P < .05).
      The TAC and IPC + TAC groups down-regulated intestinal expression of interleukin
      (II)-6 and IL1b more than 10-fold compared with the control group. Although IPC
      and TAC alone reduced intestinal IRI, the used of a combined therapy produced the
      most significant results in all the local and distant evaluated parameters. 

PMID- 23953567
TI  - Luminescence-based assay to screen preservation solutions for optimal ability to
      maintain viability of rat intestinal grafts.
AB  - BACKGROUND: Segmental intestinal transplantations from living, genetically
      related donors provide advantages compared with those from cadaveric subjects.
      However, successful preservation during ischemic cold storage is critical for
      living donor grafts. Thus, the development of preservation solutions that
      maintain graft viability is essential for success. Herein we have reported
      application of a cell-based viability assay in multiwell plates to assess the
      effectiveness of various solutions to preserve intestinal grafts. METHODS:
      Freshly isolated intestinal chips from luciferase transgenic rats were placed in
      96-well tissue culture plates for incubation at 4 degrees C for 24 hours in
      various preservation solutions: ET-Kyoto (ET-K), University of Wisconsin (UW)
      solution, Euro-Collins (EC) solution, histidine-tryptophan-ketoglutarate (HTK)
      solution, lactated Ringer's (LR) solution, or saline. RESULTS: As indicated by a
      higher level of luminescence, intestinal chips preserved in UW, HTK, or ET-K
      solution contained more viable cells, than those preserved in EC, LR, or saline
      solution. After exposure to the preservation solutions for 1 hour, the mucosal
      layer chips showed lower cell viability than the muscle layer chips. CONCLUSION:
      Our data demonstrated that ET-K and UW solutions used together with intestinal
      chips of Luciferase transgenic rat and in vivo imaging provided optimal viability
      during ischemic cold storage prior to transplantation. Further development of
      preservation conditions to minimize the loss of viability of intestinal grafts
      before clinical transplantation is essential to improve outcomes.

PMID- 23953568
TI  - Role of hydroxyethyl starch in ischemia-reperfusion injury in rat intestinal
      transplantation.
AB  - OBJECTIVE: This study was designed to evaluate the role of 0%, 3%, 6%
      hydroxyethyl starch (HES) and University of Wisconsin (UW) perfusion and
      preservation solutions on ischemia-reperfusion injury (IRI) of rat intestinal
      transplantations, solutions, respectively. MATERIALS AND METHODS: Rats underwent
      orthotopic intestinal transplantation (Lewis to Lewis) after using perfusion and
      preservation saline (group l), 3% HES (group 2), 6% HES (group 3), or UW (group
      4) solutions. The change in weight was recorded from preoperative to
      postoperative day (POD) 30. At 30 minutes after reperfusion, we harvested
      intestinal juice preoperatively as well as at 30 minutes after reperfusion and on
      POD 1 and 3 when recipients underwent open surgery for maltose absorption tests
      and sampling. The Park' scores of IRI were evaluated by light microscopy after
      hematoxylin and eosin (H&E) staining. RESULTS: An increased weight was more
      evident in group 2 than the other groups, particularly the on POD 1 and POD 3 (P
      < .05). It was significantly greater than groups 1 and 3 on POD 7 (P < .05).
      Compared with the other groups, the 30-minute post-reperfusion. Park score and
      intestinal juice content in group 2 was decreased significantly (P < .01), while
      in group 3 the Park score was increased, and the maltose absorption level
      decreased significantly (P < .05). CONCLUSION: Three percent HES solution
      attenuated IRI in rat intestinal transplantation. High-concentration HES
      solutions were unfit for intestinal preservation. Thus the adverse effects of UW
      solution may be attribute at least in part to its high HES, concentration.

PMID- 23953569
TI  - Roles of neuronal nitric oxide synthase and inducible nitric oxide synthase in
      intestinal transplantation of rats.
AB  - OBJECTIVE: The study was designed to evaluate the role of neuronal nitric oxide
      synthase (nNOS) and inducible nitric oxide synthase (iNOS) in ischemia
      reperfusion injury (IRI) and acute rejection (AR) in rat intestinal
      transplantation, by administration of nitric oxide inhibitor N(G)-nitro-L
      arginine methyl ester (LNAME). MATERIALS AND METHODS: Rats that underwent
      orthotopic intestinal transplantation were assigned to 2 sets of groups: (1) iso
      geneic group (Lewis-Lewis), L-NAME 0 mg/kg/d group (1-1), 4 mg/kg/d (group 1-2),
      or 8 mg/kg/d (group 1-3) injected intraperitoneally or (2) allogeneic group (Dark
      Agouti-Lewis), L-NAME 0 mg/kg/d (group 2-1) or 8 mg/kg/d (group 2-2) injected
      intraperitoneally. We examined survival times, light microscopy as well as
      maltose absorption tests. The nNOS and iNOS activities were measured by
      immunohistochemical methods. RESULTS: Histologic examination showed inhibited
      iNOS activity compared with group l-l, and Park scores decreased significantly in
      group 1-2 at 30 minutes after reperfusion (1.42 +/- 0.38 vs 2.58 +/- 0.49, P <
      .01). Both iNOS and nNOS activities were inhibited and Park scores increased
      significantly in group 1-3 from 30 minutes to day 3 after reperfusion (P < .0l).
      nNOS activity decreased and iNOS activity increased among group 2-1 during AR.
      Compared with group 2-1, iNOS activity was inhibited, progression of AR delayed,
      and survival significantly prolonged in group 2-2 (10.17 +/- 0.98 vs 6.83 +/-
      0.75, P < .01). CONCLUSION: This study suggested that decreased nNOS and
      increased iNOS activity both contributed to IRI and AR. More importantly, nNOS
      more importantly than iNOS activity was closely related to graft structure and
      function.

PMID- 23953570
TI  - Bupropion reduces the inflammatory response and intestinal injury due to ischemia
      reperfusion.
AB  - Intestinal ischemia-reperfusion (I/R) causes severe organ failure and intense
      inflammatory responses, which are mediated in part by the cytokine tumor necrosis
      factor-alpha (TNF-alpha). Bupropion is an antidepressant known to inhibit TNF
      alpha production. We sought to examine the protective effects of bupropion on
      intestinal I/R injury in 15 male Sprague-Dawley rats that were randomized to sham
      surgery, 45 minutes of intestinal ischemia followed by 180 minutes reperfusion,
      or bupropion (100 mg/kg) before the intestinal I/R injury. To evaluate the
      systemic inflammatory response induced by intestinal I/R, we measured serum
      levels of TNF-alpha, interleukins-1 and -6, lipid peroxidation, and
      transaminases. Histologic analysis evaluated intestinal injury using the Chiu
      muscosal injury score. After I/R, Chiu score in control animals was 3.6 +/- 1.2
      vs 2.6 +/- 0.53 in animals that received bupropion (P < .05). Bupropion
      pretreatment reduced intestinal. I/R injury and blunted serum elevations of TNF
      alpha (0.96 +/- 1.1 ng/mL vs 0.09 +/- 0.06 ng/mL, P < .05) and interleukin-1
      (0.53 +/- 0.24 ng/mL vs 0.2 +/- 0.11 ng/mL, P < .05). Bupropion in reduced
      intestinal I/R injury through immunomodulatory machanisms that involve
      inflammatory cytokines such as TNF-alpha. 

PMID- 23953571
TI  - Oxytocin ameliorates the immediate myocardial injury in rat heart transplant
      through downregulation of neutrophil-dependent myocardial apoptosis.
AB  - BACKGROUND: Cardiac oxytocin (OT) is structurally identical to that found in the
      hypothalamus, indicating that this active form of OT is derived from the same
      gene. The abundance of OT and its receptors in atrial myocytes suggests that,
      directly and/or via the release of the cardiac hormone atrial natriuretic
      peptide, this hormone regulates the force of cardiac contractions. Previous
      studies have demonstrated a role of OT in myocardial inflammatory responses. We
      sought to study protective myocardial and anti-inflammatory effects of OT in the
      immediate post-transplant period. METHODS: We grouped adult male Albino rats into
      sham, control, and OT-treated groups. Control and treated groups underwent
      heterotopic cervical heart transplantation. Myocardial injury was assessed by
      measuring plasma cardiac troponin I, and myocardial proinflammatory cytokines as
      well as by performing histopathologic assessments injury score, and of apoptotic
      degree. Myocardial myeloperoxidase, neutrophil infiltration, neutrophil
      chemotactic mediators as well as formation of reactive oxygen and reactive
      nitrogen species were measured in the myocardium at 3 hours after reperfusion to
      assess neutrophil-dependent myocardial injury. RESULTS: OT downregulates
      neutrophil chemotactic molecules--KC/CXCL1 and MIP-2/CXCL2. The decrement in
      myocardial PMN infiltration was associated with reduced reactive oxygen and
      reactive nitrogen species formation in the myocardium at 3 hours after
      reperfusion following global ischemia. OT reduced postmyocardial
      ischemia/reperfusion apoptotic processed. CONCLUSION: OT ameliorated immediate
      myocardial injury in heart grafts, through downregulation of the inflammatory
      response, of reactive oxygen species, and of neutrophil dependent apoptosis.

PMID- 23953572
TI  - NKG2D blockade significantly attenuates ischemia-reperfusion injury in a cardiac
      transplantation model.
AB  - BACKGROUND: NKG2D (natural killer group 2 member D), are activating or
      coactivating receptor on NK cells, gammadelta T, and CD8(+) T cells, stimulates
      cytokine secretion by the former two and plays a costimulatory role for the last
      CD8(+) T cells. METHODS: Male Lewis rat hearts were flushed and stored in cold
      Bretschneider preservation solution for 8 hours. Anti-NKG2D monoclonal antibody
      (mAb) was administered before transplantation into syngeneic recipients.
      Expressions of Troponin-T, myeloperoxidase (MPO), tumor necrosis factor (INF),
      (ICAM) and interleukin (IL)-17 were examined on days 1, 3, and 7 after
      reperfusion. RESULTS: We observed that isografts from anti-NKG2D mAb-treated
      animals showed decreased cardiac troponin-T, low expression of MPO, TNF, and
      ICAM, and superior cardiac output. Furthermore, blockade of NKG2D significantly
      reduced the number of gammadelta T cells, which are the main source of IL-17
      production. CONCLUSION: Blockade of NKG2D significantly attenuated ischemia
      reperfusion injury in a cardiac transplantation model. The effect coincided with
      a low expression of TNFalpha, ICAM and a reduced number of infiltrating IL-17
      producing gammadelta T cells.

PMID- 23953573
TI  - A review of various techniques of mouse liver transplantation.
AB  - OBJECTIVES: Liver transplantation in a mouse model is a valuable tool for
      studying transplantation immunobiology and clinic-relevant issues. However, the
      successful establishment is highly technical and demanding, impeding its
      widespread use. Herein, the aims of this study were to review and analyze the
      various techniques of liver transplantation in mice to circumvent pitfalls and
      minimize the incidence of complications. MATERIALS AND METHODS: A search of
      PubMed was made by using the key words "mouse liver transplantation" for articles
      published between January 1973 and July 2012. Of the 473 publications identified,
      14 were shown to be closely associated with mouse liver transplantation and 4
      articles discussed specific microsurgical techniques. Through reviewing these
      articles, a series of potential factors were collected and analyzed in
      combination with other murine transplantation models, which might influence
      successfully establishing a mouse model for liver transplantation. RESULTS: A
      mouse liver transplantation model is feasible and practical for experimental
      studies. Mouse strain, type of anesthesia, type of perfusion and storage
      solution, and reconstruction of bile duct are relevant factors but not
      determinants for a successful transplantation. Cold and warm ischemia time should
      be less than 4.0 hours and 20 minutes, respectively. CONCLUSIONS: The cuff
      preparation, reconstruction of the hepatic artery, and length of the anhepatic
      phase play critical roles in successfully establishing a liver transplantation
      model in mice.

PMID- 23953574
TI  - A simple technique for a new working heterotopic heart transplantation model in
      rats.
AB  - OBJECTIVE: A new working model of heterotopic heart transplantation in rats was
      established using a simplified technique. MATERIALS AND METHODS: Sprague-Dawley
      rats were used as donors and recipients. The donor left common carotid artery and
      left pulmonary artery were anastomosed to the recipient left renal artery and
      vein by a "sleeve and cuff" method, respectively. The donor left ventricle was
      blood volume loaded by anastomosing the left atrium to the recipient's abdominal
      aorta in end-to-side fashion. The characteristics of the donor heart were
      evaluated by palpating the abdominal wall of the rats. We examined the surgical
      success rate, changes in heart weight, and histology at 1 month after
      transplantation. RESULTS: The model was attempted in 32 rats with the success
      rate of 93.7% (30/32); the 2 failed cases died due to postoperative bleeding.
      There was no significant difference in mean weight changes between the donor and
      native hearts at 1 month after transplantation (1.13 +/- 0.13 g vs 1.09 +/- 0.12
      g, P = .244). The donor heart myocardium showed regularly shaped, unidirectional,
      healthy muscle similar to the native heart. CONCLUSIONS: The technique was easily
      learned, allowing less recipient surgical stress. The hemodynamic performance
      appeared to be similar to the normal cardiac physiological situation, and thus
      may be more suitable for pre-clinical studies.

PMID- 23953575
TI  - The protection and therapy effects of bortezomib in murine acute graft-versus
      host disease.
AB  - Acute graft-versus-host disease (aGVHD) remains a life-threatening complication
      after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The
      proteasome inhibitor bortezomib exhibits potent antitumor activity with anti
      inflammatory and immunomodulatory effects. However, the effects of bortezomib on
      aGVHD are unclear. In this study, we assessed the effects of bortezomib on aGVHD
      in the C57BL/6 (H-2b+) donor to BALB/c (H-2d+) recipient major histocompatibility
      complex-mismatched model. Two bortezomib doses (1 mg/kg each) on days 0 and +1
      after transplantation, significantly increased survival rate and attenuated
      clinical signs of aGVHD without altering donor reconstitution. However, GVHD
      associated mortality was significantly increased when bortezomib administration
      was delayed to day +2 posttransplantation. Furthermore, a single dose of
      bortezomib on day 0 or day +1 after transplantation also decreased the GVHD
      protective effect. Consistent with the above data, serum cytokine levels of IL-2,
      IFN-gamma and TNF-alpha were significantly decreased at day +7
      posttransplantation after two doses of bortezomib compared with aGVHD control
      group. Moreover, two administrations of bortezomib reduced donor T-cell expansion
      at days +3 and +4 posttransplantation and enhanced donor CD4(+)T-cell
      differentiation into the T help cell 17 subset at day +7 after transplantation in
      spleens. These results indicated that the protective effects of bortezomib on
      aGVHD were dependent on the time and the frequency of bortezomib administration. 

PMID- 23953576
TI  - Cytomegalovirus infection accelerates the process of chronic rejection in rat
      liver transplantation.
AB  - OBJECTIVE: Analysis of the pathogenesis of cytomegalovirus (CMV) infection for
      rat chronic liver rejection. METHODS: Based on animal models that we previously
      developed, we divided control and a CMV infection group to analyze survival,
      histopathology and rejection activity. The level and mRNA expression of
      transforming growth factor-beta1, platelet-derived growth factor (PDGF), basic
      fibroblast growth factor (bFGF) were measured in peripheral blood serum and liver
      tissue. RESULTS: Obliterative arteriopathy and fibrosis was significantly greater
      in the CMV infection versus the control group (P < .05). PDGF mRNA expression in
      rat liver and in peripheral blood were significantly higher in the CMV infection
      versus the control group (P < .05). bFGF mRNA expression in the CMV infection
      group was also significantly higher than among the controls (P < .05).
      CONCLUSIONS: CMV infection aggravated foam cell obliterative arteriopathy and
      liver fibrosis in chronic liver rejection, processes that accelerate the immune
      response, which may correlate with early high PDGF and bFGF expression.

PMID- 23953578
TI  - Postoperative enteral nutrition improves survival after orthotopic small bowel
      transplantation in mice.
AB  - BACKGROUND: The aim of this study was to assess the effect postoperative enteral
      nutrition support on the survival after orthotopic small bowel transplantation in
      mice. METHODS: A model of orthotopic small bowel transplantation used C57BL/6
      mice as both donors and recipients. RESULTS: We demonstrated that postoperative
      ileus was the deciding complication after transplantation. Postoperative enteral
      nutritional support resolved this problem and significantly improved survival and
      growth rates after transplantation. CONCLUSION: These data suggest the importance
      of routine nutritional support after orthotopic small bowel transplantation in
      mice.

PMID- 23953577
TI  - Cell stress response in rat chronic small bowel allograft rejection.
AB  - BACKGROUND: We sought to assess the expression of five cell stress molecules:
      Heat shock protein (HSP)-60, HSP-70, interferon (IFN)-alpha, rat retinoic acid
      early induible-1 like transcript (RRLT), and vasoactive intestinal peptide (VIP)
      during rat chronic small bowel allograft rejection. METHODS: A rat model of small
      bowel allograft rejection was induced on postoperative day 90 using F344 rat as
      donor and Lewis rat as recipient. RESULTS: We demonstrated increased expression
      of lamina propria HSP-60 (mean rank grade 8.3 and 3.2, respectively), graft RRLT
      (relative mRNA amount 5.1 +/- 1.8 and 3.0 +/- 1.3, respectively) and IFN-alpha
      (relative mRNA amount 108.3 +/- 49.2 and 59.2 +/- 22.0, respectively) in
      allograft group compared with the isograft group. CONCLUSION: These data suggest
      the presence of cell stress during chronic small bowel allograft rejection.

PMID- 23953579
TI  - Chronic allograft nephropathy in rats is improved by the intervention of rhein.
AB  - AIM: In this study, we investigated the therapeutic efficacy and potential
      mechanisms of rhein to mitigate chronic allograft nephropathy (CAN) in rats.
      MATERIALS AND METHODS: Fisher rat donors and Lewis rat recipients were used to
      establish the CAN model. Thirty rats with transplanted kidneys were randomly
      divided into two groups: 16 untreated and 14 rhein = treated rats. Five Lewis rat
      controls underwent removal of their right kidneys. The Intervention group was
      administered rhein oral solution (100 mg kg(-1) d(-1)) by gavage after
      transplantation. The untreated and control groups were given 0.5% sodium
      carboxymethyl cellulose. Blood and urine samples were collected at 4, 8, and 16
      weeks to examine renal function and total urine protein. Half of the rats in each
      group were sacrifice at 8 or 16 weeks to examine renal pathology.
      Immunohistochemical examination and real-time polymerase chain reaction of renal
      tissues were performed to detect expressions of transforming growth-beta1(TGF
      beta1), hepatic growth factor (HGF), bone morphogenetic protein 7 (BMP7),
      frobronectin, and collgen IV. RESULTS: Rhein improved renal function and
      significantly reduced renal fibrosis and interstitial inflammation. The levels of
      BMP7 and HGF were significantly elevated in the renal tissues of the rhein
      intervention group. In the meantime, fibronectin and collagen IV were decreased
      in the extracellular matrix. The expression of TGF-beta1 was similar between
      these two groups. CONCLUSION: Rhein improved renal function and reduced renal
      fibrosis and interstitial inflammation by inducing production of HGF and BMP7.

PMID- 23953580
TI  - Small interfering RNA targeting nuclear factor kappa B to prevent vein graft
      stenosis in rat models.
AB  - BACKGROUND: Intimal hyperplasia plays an important role in vein graft stenosis.
      Inflammatory injury, especially nuclear factor kappaB (NF-kappaB) gene
      activation, is highly involved in stenosis progression. We examined whether
      neointimal hyperplasia and vein graft stenosis could be inhibited by silencing
      the NF-kappaB gene with small interference RNA (siRNA). METHODS: Sixty adult male
      Sprague-Dawley rats were randomly divided into a normal vein group, a vein graft
      group, a scrambled siRNA group, and an NF-kappaB siRNA group. We performed
      reverse interpositional grafting of the autologous external jugular vein to the
      abdominal aorta. Vein grafts were treated with liposome and gel complexes
      containing NF-kappaB siRNA or scrambled siRNA. The levels of monocyte
      chemoattractant protein -1, tumor necrosis factor-alpha, and NF-kappaB p65 in
      vessel tissues were evaluated after surgery for content of proliferating cell
      nuclear antigen (PCNA) and vascular wall thickness. RESULTS: NF-kappaB siRNA
      treated vein graft showed less neointimal formation and fewer positive PCNA cells
      (P < .05). In addition there were lower levels of, NF-kappaB p65 protein and of
      inflammatory mediators (P < .05) compared with the vein graft group. CONCLUSION:
      Our study suggested that siRNA transfection suppressed NF-kappaB expression,
      reduced inflammatory factors, lessened neointimal proliferation, and suppressed
      PCNA.

PMID- 23953581
TI  - Cyclosporine combined with nonlytic interleukin 2/Fc fusion protein improves
      immune response to hepatitis B vaccination in a mouse skin transplantation model.
AB  - BACKGROUND: Improving immune responses to vaccination in immunosuppressed
      patients is extremely important. Previously, we observed that cyclosporine (CsA)
      combined with a nonlytic interleukin (IL)-2/fragment crystallizable (Fc) fusion
      protein induces immune tolerance to mouse skin transplantations. In the present
      study, we asked whether this combination improved hepatitis B (HBV) vaccine
      efficacy in immunosuppressed mice while also prolonging skin graft survival.
      METHODS: After C57BL/6 mice received DBA/2 skin grafts, they were administered a
      14-day course of CsA (30 mg/kg intraperitoneal) combined with IL-2/Fc (1 MUg,
      intraperitoneal). HBV vaccine (2 MUg) was injected intramuscularly on the day of
      skin transplantation. On day 14, the serum levels of hepatitis B surface antibody
      (HBsAb), IL-4, IL-10, interferon (IFN-gamma), and IL-2 were measured by enzyme
      linked immunosorbent assay. We assessed the percentages of CD4(+)CXCR5(+)
      follicular T helper cells, CD4(+)FoxP3(+) regulatory T cells (Treg) and
      expressions of IL-17, IL-21, FoxP3, Bcl-6 in the spleen. Animals were divided
      into four groups: control, vaccine-treated, CsA + vaccine-treated, CsA + IL-2/Fc
      + vaccine-treated hosts. RESULTS: Combination therapy significantly increased
      HBsAb levels and also prolonged skin graft survival. Serum levels of Th1
      cytokines IL-2 and IFN-gamma were significantly higher in the combination group,
      while Th2 cytokines, IL-4 and IL-10 were lower. Combined treatment increased the
      percentage of Treg and the expression of Foxp3 and IL-21, meanwhile inhibiting
      the expression of Bcl-6. But the percentage of Tfh did not significantly change
      among the groups. CONCLUSIONS: These observations suggested that a combination of
      CsA and IL-2/Fc fusion protein enhanced immune responses after HBV vaccination
      and prolonged skin graft survival.

PMID- 23953582
TI  - Blockade of OX40/OX40 ligand to decrease cytokine messenger RNA expression in
      acute renal allograft rejection in vitro.
AB  - AIM: The aim of this study was to investigate cytokine messenger RNA (mRNA)
      expression by peripheral blood mononuclear cells (PBMCs) from renal recipients
      experiencing acute rejection by blocking OX40-OX40L interactions with recombinant
      human OX40-Fc fusion protein (rhOX40Fc) in vitro. METHODS: PBMCs were isolated
      from 20 recipients experiencing acute rejection episodes (rejection group) and 20
      recipients with stable graft function (stable group). Levels of Th1 (interferon
      [IFN]-gamma) and Th2 (interleukin [IL]-4) mRNA expressions by PBMCs were measured
      using real-time reverse transcriptase-polymerase chain reactions. RESULTS: IFN
      gamma mRNA expression levels were significantly higher in the rejection than the
      stable group (P < .05). Levels of IL-4 mRNA expression were not significantly
      different. Among the rejection group, rhOX40Fc reduced significantly the
      expression of IFN-gamma and IL-4 mRNA by anti-CD3-monoclonal antibody stimulated
      PBMCs (P < .05, and P < .01, respectively). CONCLUSIONS: Blocking of the
      interaction between OX40 and OX40L in vitro inhibited production of Thl and Th2
      type cytokines.

PMID- 23953583
TI  - High live birth rate in the subsequent IVF cycle after first-cycle poor response
      among women with mean age 35 and normal FSH.
AB  - Poor ovarian response in IVF cycles is associated with diminished ovarian reserve
      and poor pregnancy outcome. Little is known about pregnancy outcome after a poor
      response in women with a normal ovarian reserve. This retrospective study studied
      women undergoing IVF/intracytoplasmic sperm injection between January 2003 to
      December 2008 in the FertilityPLUS Clinic in Auckland, New Zealand. All women
      with a poor response in the first cycle were selected. Primary outcome was live
      birth after the second cycle. Secondary outcomes were poor response in the second
      cycle and the predictive values of female age and basal FSH at first cycle and
      IVF outcome at second cycle. Of the 2487 women starting IVF, 142 women (5.7%)
      with a poor response in the first cycle were selected, of which 66 (46.5%) women
      had a repeated poor response in the second cycle. There were 31 live births in
      the second cycle (21.8%). Female age was the only significant predictor for
      repeated poor response (AUC 0.69, 95% CI 0.61-0.78) and clinical pregnancy (AUC
      0.66, 95% CI 0.57-0.75), but the predictive value was low. Therefore poor
      response in women with a normal ovarian reserve should not be a reason to
      discontinue further IVF treatment. Poor ovarian response in IVF cycles is
      associated with diminished ovarian reserve and poor pregnancy outcome. Little is
      known about pregnancy outcome after a poor response in women with a normal
      ovarian reserve. In this retrospective study, we studied women undergoing
      IVF/intracytoplasmic sperm injection (ICSI) between January 2003 to December 2008
      in the FertilityPLUS Clinic in Auckland, New Zealand. All women with a poor
      response in the first cycle were selected. Primary outcome was live birth after
      the second cycle. Secondary outcomes were poor response in the second cycle and
      the predictive value of female age and basal FSH at first cycle and IVF outcome
      at the second cycle. Of the 2487 women starting wit IVF, a total of 142 women
      (5.7%) with a poor response in the first cycle were selected, of which 66 (46.5%)
      women had a repeated poor response in the second cycle. There were 31 live births
      in the second cycle (22%). Female age was the only significant predictor for
      repeated poor response and clinical pregnancy, but the predictive value was low.
      Therefore poor response in women with a normal ovarian reserve should not be a
      reason to discontinue further IVF treatment. 

PMID- 23953584
TI  - Oocyte insemination techniques are related to alterations of embryo developmental
      timing in an oocyte donation model.
AB  - Because of the different intrinsic characteristics of the classic IVF and
      intracytoplasmic sperm injection (ICSI) techniques, the timing of zygote
      development can be influenced by the method of fertilization. However, there is
      no information about the relevance of the insemination procedure on embryo
      quality parameters as measured through their developmental dynamics. The aim of
      this work was to determine if the insemination technique, IVF or ICSI, influences
      embryo developmental kinetics by examining 1203 embryos from 178 couples
      undergoing oocyte donation with IVF or ICSI. Using time-lapse information, this
      work calculated several developmental kinetic variables, from pronuclear fading
      (PNF) to expanded blastocyst, and also the proportion of optimal embryos in a
      best time range with a predicted higher implantation potential. Embryo
      development after ICSI was slightly faster than after IVF; however, when PNF,
      rather than time of insemination, was established as t0, the differences between
      the two procedures disappeared. The percentage of optimal embryos showed a trend
      towards higher values in IVF-derived embryos; however, the difference was not
      statistically significant. With these results and through the time-lapse
      monitoring system, it is concluded that it is the fertilization method which
      determines embryo developmental kinetics if insemination time is used as the
      starting point. A key step in assisted reproduction is the assessment of oocyte
      and embryo viability to determine the embryo(s) most likely to implant. Current
      embryo assessment strategies in clinical settings largely rely on embryo
      morphology and cleavage rates, and although these systems have been successful in
      improving pregnancy rates, their precision is far from ideal as they are based on
      visual information. In contrast, automated image analysis may add objectivity to
      the process of embryo selection and consequently, lead to an improvement in the
      implantation rates. Timing of zygote development can be influenced by the method
      of fertilization or by in-vitro culture conditions, so it has been suggested that
      the fertilization procedure influences the length of time elapsed between
      fertilization and the first cleavage. In this report, we show the results from
      using a time-lapse monitoring system to determine the timing of key events during
      embryo development both in IVF and ICSI. Due to the different intrinsic
      characteristics of the classic IVF and ICSI techniques, the selection of a
      critical time point is essential so as to maximize the differences between the
      two methods. For that reason, we searched for evidence in the data obtained from
      the image analysis for a link connecting embryo cleavage and the fertilization
      technique and also to find whether the kinetic of development derived from
      classic IVF or ICSI is also related to a predicted higher implantation. 

PMID- 23953585
TI  - Association between blastocyst morphology and outcome of single-blastocyst
      transfer.
AB  - The aim of this study was to assess the ability of three individual blastocyst
      morphology parameters - expansion and hatching (EH) stage, inner cell mass (ICM)
      grade and trophectoderm grade - to predict outcome of a cycle with single
      blastocyst transfer. The study was a secondary analysis of data prospectively
      collected in a large multicentre trial. A total of 618 intracytoplasmic sperm
      injection patients undergoing ovarian stimulation in a gonadotrophin-releasing
      hormone antagonist cycle with compulsory single-blastocyst transfer on day 5 were
      included. In the simple logistic regression analysis, all three blastocyst
      morphology parameters were statistically significantly (P<0.005 for each)
      associated with positive human chorionic gonadotrophin, clinical and ongoing
      pregnancy rates and live birth rates, while only the ICM grade was significantly
      (P=0.033) associated with early pregnancy loss rate. Blastocyst EH stage was the
      only significant predictor of live birth (P=0.002) in the multiple logistic
      regression. In conclusion, although all three blastocyst morphology parameters
      were related to treatment outcome of fresh single-blastocyst cycles, selection of
      high-quality blastocysts for transfer should consider first the EH stage.
      Transfer of a blastocyst with ICM grade A may reduce the risk of early pregnancy
      loss. Choosing the embryo(s) with the best implantation potential is essential
      for securing each couple the highest chance of achieving pregnancy after assisted
      reproduction. The selection of embryo(s) for transfer at the blastocyst stage is
      based on morphology parameters of expansion and hatching stage, inner cell mass
      grade and trophectoderm grade. The aim of this study was to assess the relative
      impact of each parameter in predicting the probability of a successful outcome.
      The study was a secondary analysis of data prospectively collected in a large
      multicentre trial. A total of 618 patients who underwent single-blastocyst
      transfer on day 5 were included. Statistical analysis showed that all three
      blastocyst morphology parameters were significantly associated with positive
      human chorionic gonadotrophin (betaHCG), clinical and ongoing pregnancy rates and
      live birth rates. Only the inner cell mass grade was significantly associated
      with early pregnancy loss between the positive betaHCG test and confirmation of
      ongoing pregnancy 10-11weeks after transfer. The expansion and hatching stage was
      the only significant predictor of live birth in the multiple logistic regression
      analysis. In conclusion, although all three blastocyst morphology parameters were
      related to treatment outcome of fresh single-blastocyst cycles, selection of high
      quality blastocysts for transfer should consider first the expansion and hatching
      stage. Transfer of a blastocyst with inner cell mass grade A may reduce the risk
      of early pregnancy loss. 

PMID- 23953586
TI  - Risk of ectopic pregnancy following day-5 embryo transfer compared with day-3
      transfer.
AB  - The incidence of ectopic pregnancy after IVF is increased approximately 2.5-5
      fold compared with natural conceptions; however, the aetiology for this increased
      risk remains unclear. One proposed practice change to decrease the incidence of
      ectopic pregnancy is blastocyst embryo transfer on day 5 rather than cleavage
      stage embryo transfer on day 3. A retrospective cohort study was conducted to
      compare the risk of ectopic pregnancy following fresh day-5 embryo transfer with
      day-3 embryo transfer among women who underwent IVF and achieved pregnancy from
      1998 to 2011. There were 13,654 eligible pregnancies; 277 were ectopic. The
      incidence of ectopic pregnancy was 2.1% among day-3 pregnancies and 1.6% among
      day-5 pregnancies. The adjusted risk ratio for ectopic pregnancy from day-5
      compared with day-3 transfer was 0.71 (95% confidence interval 0.46-1.10).
      Although this analysis included 13,654 cycles, with a two-sided significance
      level of 0.05, it had only 21.9% power to detect a difference between the low
      incidence of ectopic pregnancy among both day-3 and day-5 transfers. In
      conclusion, this study was not able to demonstrate a difference in the risk of
      ectopic pregnancy among day-3 compared with day-5 transfers. 

PMID- 23953587
TI  - Replacement of sodium with choline in slow-cooling media improves human ovarian
      tissue cryopreservation.
AB  - Ovarian tissue cryopreservation is a promising technique for fertility
      preservation in young female cancer patients and efforts have been made to
      improve its effectiveness. During cooling and thawing, sodium ions significantly
      contribute to the 'solute effect' that plays a major role in disrupting cell
      membranes. Choline ions, which do not cross the cell membrane, should not
      contribute to the intracellular solute load. The present study assessed the
      effects of sodium substitution with choline in slow-cooling freezing media on
      human ovarian cortical strip cryopreservation. A total of 629 follicles (fresh
      control n=266; cryopreserved n=363), collected from ovarian biopsies of 11 women
      (22-40years) during laparoscopic surgery, were studied by light microscopy,
      immunohistochemistry and transmission electron microscopy to evaluate their
      morphology, apoptosis and ultrastructure. The results demonstrate that choline
      substitution leads to: (i) an improved preservation of oocytes and follicular
      cells; (ii) the recovery of a higher percentage of grade-1 follicles negative for
      p53, p21 and Apaf-1 apoptotic markers; (iii) a reduced mitochondrial damage as
      observed at an ultrastructural level; and (iv) a better preservation of ovarian
      tissue stroma. In conclusion, the use of choline-based media may represent a
      valuable tool to improve human ovarian tissue cryopreservation. Ovarian tissue
      cryopreservation is a promising fertility preservation approach for cancer
      patients before undergoing treatments that irreversibly reduce the ovarian
      reserve. Autotransplantation of ovarian cortical strips has resulted in viable
      offspring in animal models and human. Worldwide, 20 live births have been
      reported thus far following autotransplantation of frozen-thawed ovarian tissue.
      However, currently the success rate of this technology is far from being
      satisfactory. This could be due to inappropriate cryopreservation procedures that
      might impair the physiology of ovarian follicles. Sodium ions contained in
      freezing media significantly contribute to the 'solute effect' that plays a major
      role in disrupting cell membranes. Choline ions, which do not cross the cell
      membrane, would not be expected to contribute to the intracellular solute load.
      In the present study we assessed the effects of sodium substitution with choline
      in slow-cooling freezing media on human ovarian cortical strip cryopreservation.
      A total of 629 follicles, collected from ovarian biopsies of 11 women (aged 22
      40years) during laparoscopic surgery, have been studied by light microscopy,
      immunohistochemistry and transmission electron microscopy to evaluate their
      morphology, apoptosis and ultrastructure. Results demonstrated that choline
      substitution allowed: (i) a better preservation of oocytes and follicular cells;
      (ii) the recovery of an higher percentage of healthy follicles negative for
      apoptotic markers; (iii) a lower mitochondria ultrastructural damage; and (iv) a
      better preservation of ovarian tissue stroma. In conclusion, the use of choline
      based media could represent a valuable tool to cryopreserve human ovarian tissue
      for fertility preservation. 

PMID- 23953588
TI  - Association of allelic combinations of FSHR gene polymorphisms with ovarian
      response.
AB  - During an IVF protocol, exogenous FSH is administered to women for ovulation
      induction. The ovarian response to gonadotrophin stimulation is variable and
      unpredictable in these women. The FSHR is the most studied gene in relation to
      ovarian response. The association of a FSHR gene polymorphism at position 680
      (p.Asn680Ser) with ovarian response has been well documented. Recently, a
      polymorphism at position -29 in the 5'-untranslated region of FSHR (g.-29G>A) has
      been reported to be associated with poor ovarian response and reduced FSHR
      expression. The present study evaluated the combined effect of the polymorphisms
      at positions -29 and 680 of FSHR with type of ovarian response and receptor
      expression. The two FSHR gene polymorphisms together formed four discrete
      haplotypes and nine allelic combinations. Various clinical parameters revealed
      that 75% of the subjects with A/A-Asn/Asn genotype were poor ovarian responders
      (odds ratio 7.92; P=0.009). The relative FSHR mRNA expression in granulosa cells
      indicated that subjects with A/A-Asn/Asn genotype express significantly lower
      level of FSHR as compared to the subjects with G/G-Asn/Ser genotype (P=0.029).
      These results indicate that A/A-Asn/Asn genotype could be used as a potential
      marker to predict poor ovarian response. The action of FSH is mediated by its
      receptor (FSHR) present on the granulosa cells in the ovary. Any alterations in
      the hormone or its receptor are likely to disrupt its normal function, thus
      causing infertility. Several alterations (mutations/polymorphisms) of the FSHR
      gene have been reported in women with primary or secondary amenorrhoea. It has
      also been reported that FSHR gene polymorphisms are associated with variable
      ovarian response to FSH stimulation during IVF. Women may show poor or normal or
      hyperovarian response to FSH stimulation. It is well documented that the level of
      FSHR expression has a great effect on FSH action and is associated with ovarian
      response. In the present study, we screened normally menstruating women
      undergoing IVF due to tubal/male factor or unexplained infertility. We analysed
      two polymorphisms of FSHR, g-29G>A and p.Asn680Ser, in these women. In the
      subjects studied, 75% women with A/A-Asn/Asn genotype were observed to be poor
      ovarian responders to FSH stimulation. FSHR expression at the transcript level
      was observed to be significantly lower in women with A/A-Asn/Asn genotype as
      compared to women with G/G-Asn/Ser genotype. We also observed that women with A/A
      Ser/Ser genotype were not present in the study population. These findings
      indicate the significance of A/A-Asn/Asn genotype as a predictive marker for poor
      ovarian response to FSH stimulation. 

PMID- 23953589
TI  - Association of AQP8 in women with PCOS.
AB  - Aquaporin 8 (AQP8) has been identified as a novel gene participating in female
      reproductive physiology. The present study was designed to determine whether an
      association exists between AQP8 and polycystic ovary syndrome (PCOS). This study
      recruited 192 women with PCOS and 191 controls. High-resolution melting and
      sequencing were employed to investigate the genotypes of six single-nucleotide
      polymorphisms within AQP8 (rs7198838, rs1076973, rs1076974, rs2287797, rs2287798
      and rs2287796). A significant difference was found in rs2287798 between PCOS
      cases and controls (P=0.0007). Possible associations between AQP8 genotypes and
      three different phenotypes of this syndrome were investigated. The results
      support the earlier evidence for a possible role of AQP8 in the pathogenesis of
      PCOS. Further studies are still needed to elucidate its functional role.
      Aquaporin 8 (AQP8) has been identified as a novel gene participating in female
      reproductive physiology. The present study was designed to determine whether
      there is an association between AQP8 and polycystic ovary syndrome (PCOS). This
      study recruited 192 women with PCOS and 191 controls. High-resolution melting and
      sequencing were employed to investigate the genotypes of six single-nucleotide
      polymorphisms within AQP8 (rs7198838, rs1076973, rs1076974, rs2287797, rs2287798
      and rs2287796). We observed a significant difference in allele frequency of
      rs2287798 between PCOS cases and controls (P=0.0007). The possible association
      between AQP8 genotypes and three different phenotypes of this syndrome in this
      locus were investigated. Our results support the earlier evidence for a possible
      role of AQP8 in the pathogenesis of PCOS. Further studies are still needed to
      elucidate its functional role. 

PMID- 23953590
TI  - Parastrongyloides trichosuri suggests that XX/XO sex determination is ancestral
      in Strongyloididae (Nematoda).
AB  - The parasitic roundworms Strongyloides stercoralis (in man) and Strongyloides
      ratti (in rats) employ environmentally controlled XX/XO sex determination with a
      pair of X chromosomes and two pairs of autosomes. Strongyloides papillosus (in
      sheep) has only two pairs of chromosomes, one of which combines the genetic
      material homologous to the S. ratti chromosomes X and I. This species creates
      males through the elimination of one copy of the portion related to the X
      chromosome (chromatin diminution). It is not clear which one of these two sex
      determining mechanisms is ancestral. We demonstrate that Strongyloides vituli (in
      cattle) has two pairs of chromosomes like its very close relative S. papillosus
      whereas Parastrongyloides trichosuri, a closely related out-group to
      Strongyloides spp. in Australian brushtail possums, has three chromosome pairs
      and employs XX/XO sex determination. The X chromosome of P. trichosuri is
      homologous to the X chromosome of S. ratti. Our data strongly suggest that the
      last common ancestor of Strongyloides spp. and Parastrongyloides spp. had two
      pairs of autosomes along with two or one X chromosome in females and males,
      respectively. The situation with two pairs of chromosomes is likely derived and
      occurred through the fusion of the X chromosome with an autosome.

PMID- 23953591
TI  - A rare case of clear cell sarcoma with 4 types of EWSR1-ATF1 fusions detected not
      in primary site but in metastatic site.
AB  - Clear cell sarcoma is a unique tumor which has EWSR1-ATF1 or EWSR1-CREB1 fusion.
      Several patterns of EWSR1-ATF1 fusion are observed in clear cell sarcoma. Since
      type 5-7 fusions were reported recently, they are classified as type 1-7. We
      examined EWSR1-ATF1 and EWSR1-CREB1 fusions in a single case of clear cell
      sarcoma with lung metastasis in a 36-year-old Japanese man. As a result, we found
      only type 1 EWSR1-ATF1 fusion in the primary site, but 4 types of EWS-ATF1 fusion
      (type 1, 2, 5, 6) were detected in the metastatic site. These 4 types of fusion
      were completely identical to the recent report, but the case had the same fusion
      patterns in both primary and metastatic sites. In our case, increased splicing
      activity in the EWSR1-ATF1 fusion might be acquired at the metastatic site. There
      is another possibility that metastasis might develop through the increased
      splicing activity in the fusion.

PMID- 23953593
TI  - Determining the impact of instrument variation and automated software algorithms
      on the TGT in hemophilia and normalized plasma.
AB  - BACKGROUND: Despite increasing recognition as a more precise test of in vivo
      hemostatic conditions, standardization of the thrombin generation test (TGT)
      continues to hinder its development as routine clinical practice. Prior efforts
      largely focused on comparing the effects of experimental conditions and different
      reagents. Commercialized kits, instruments and software have been introduced to
      calculate the TG curve and its parameters. However, modified versions of the TGT
      continue to be used worldwide on a variety of microplate reader instruments and
      processed using individualized algorithms. No prior study has compared the effect
      of instrument choice and its inherent noise profile on the processing of the TG
      curve and its common endpoint parameters. MATERIALS AND METHODS: Hemophilia A
      plasma supplemented with buffer or Factor VIII, mimicking hemophilic or
      normalized samples respectively, was monitored for thrombin generation after
      activation with TF on six different fluorescent microplate readers. Each
      instrument was optimized for TGT signal recording prior to testing. An automated
      software package containing various mathematical algorithms was utilized to
      compute the TG curves and parameters, and compare different TG processing
      approaches. RESULTS: Instruments produced unique noise profiles and end-point
      parameters that were incomparable in absolute signal terms. Similar relative
      hemophilic responses were obtained across various instruments when the normalized
      plasma sample was used as an internal standard. Smoothing algorithms corrected
      destructive instrument noise. CONCLUSIONS: Instrument-induced errors from
      numerical differentiation during TG curve processing cannot be eliminated by
      external calibrators, and require careful qualification of the instrument and
      implementation of noise-reducing software algorithms.

PMID- 23953594
TI  - Effect of 200MUG/day of vitamin K1 on the variability of anticoagulation control
      in patients on warfarin: a randomized controlled trial.
AB  - BACKGROUND: Controversy exists whether low-dose vitamin K supplementation can
      improve anticoagulation control in patients with unstable anticoagulation under
      warfarin. In a single- centre randomized, double-blind, placebo-controlled study,
      we evaluated the effectiveness of 200 MUg/day of vitamin K1 in patients with
      unstable control under warfarin. METHODS: Effectiveness of Vitamin K1
      supplementation was primarily assessed by the percentage (%) of Time-in
      Therapeutic-Range (TTR) and secondarily by the standard deviation (SD) of the
      patient's INR values; the proportion of out-of-range INRs; and the number of dose
      changes on warfarin. Their change scores were obtained by subtracting the mean
      value in the 6 months pre-randomization from the mean value in the 6 months post
      randomization. Multivariable linear-regressions identified factors associated
      with anticoagulation instability. RESULTS: Fifty out of 54 patients were analyzed
      (intervention: n=26; placebo: n=24). Most indications (87%) for anticoagulation
      were venous thromboembolism (VTE). The intervention was associated with a greater
      reduction in the change scores for the SD of INRs between the pre and post
      randomization periods compared with placebo. The mean change score was -0.259+/
      0.307 with the intervention and -0.046+/-0.345 with placebo (p=0.026). There was
      no effect on the change scores of the (%) TTR (p=0.98), the number of INRs out-of
      range (p=0.58) and the number of dose changes (p=0.604). Factors independently
      associated with increased variability in the SD of INRs were increased alcoholic
      drinks/week (p=0.017), dosing errors (p=0.0009) and missed INR appointments
      (p=0.035). CONCLUSION: Vitamin K1 supplementation reduces the SD of INRs as an
      indicator of the variability in anticoagulation control in patients treated with
      warfarin for VTE.

PMID- 23953592
TI  - Glucocorticoid receptor signaling in health and disease.
AB  - Glucocorticoids are steroid hormones regulated in a circadian and stress
      associated manner to maintain various metabolic and homeostatic functions that
      are necessary for life. Synthetic glucocorticoids are widely prescribed drugs for
      many conditions including asthma, chronic obstructive pulmonary disease (COPD),
      and inflammatory disorders of the eye. Research in the past few years has begun
      to unravel the profound complexity of glucocorticoid signaling and has
      contributed remarkably to improved therapeutic strategies. Glucocorticoids signal
      through the glucocorticoid receptor (GR), a member of the superfamily of nuclear
      receptors, in both genomic and non-genomic ways in almost every tissue in the
      human body. In this review, we provide an update on glucocorticoid receptor
      signaling and highlight the role of GR signaling in physiological and
      pathophysiological conditions in the major organ systems in the human body. 

PMID- 23953595
TI  - In vitro evaluation of residual procoagulants in human intravenous
      immunoglobulins from 11 Chinese blood fractionation companies.
AB  - INTRODUCTION: Residual procoagulants has been suggested to play an important role
      in the occurrence of thromboembolic events with intravenous immunoglobulin.
      OBJECTIVE: This study investigated the predominant plasma proteases in 81
      intravenous immunoglobulin lots from 11 Chinese manufacturers to examine the
      procoagulants of these human therapeutic intravenous immunoglobulin products.
      METHODS: In one-stage clotting assays, the procoagulant activities of factors II,
      VII, IX, X, XI, and XII were quantified. Non-activated partial thromboplastin
      time and a modified thrombin generation test served as global and activated
      coagulation factor XI specific clotting assays, respectively. RESULTS: The
      coagulation factor clotting activities of the 78 intravenous immunoglobulin lots
      were below the detection limit of the assays. The time to peak of thrombin
      generation using a thrombin generation test was longer than 35min. The relevant
      amount of activated coagulation factor XI was below 0.37 nM. Non-activated
      partial thromboplastin time was greater than 203s, except for the three pilot
      samples of manufacturer B in which we observed 0.48 to 0.09IU/mL factor XI lever,
      20 to 26min for the time to peak of thrombin generation, 0.54 to 37.99 nM
      activated coagulation factor XI, and 155 to 182s for non-activated partial
      thromboplastin time. CONCLUSIONS: The three intravenous immunoglobulin lots from
      manufacturer B showed significant procoagulant potential. Further study is
      required to determine whether a program for activated coagulation factor XI
      determination in intravenous immunoglobulin products should be launched in China.

PMID- 23953596
TI  - Structural perspective on the formation of ribonucleoprotein complex in negative
      sense single-stranded RNA viruses.
AB  - Negative-sense single-stranded RNA viruses (NSRVs) possess a ribonucleoprotein
      (RNP) complex composed of viral polymerase and genomic RNA surrounded by viral
      nucleoprotein. The RNP facilitates virus replication, transcription, and
      assembly. To date, a large body of structural work, through crystallography and
      electron microscopy (EM) analysis, has been performed to aid understanding the
      molecular mechanism of RNP formation in NSRVs, and provides great potential for
      the discovery of antiviral agents targeting viral RNP formation.

PMID- 23953597
TI  - Opening it up for more questions: racial disparities in hospice use.

PMID- 23953598
TI  - Analytical validation of radioimmunoassays for the quantification of select
      pancreatic enzymes in jejunal fluid and fecal extracts from dogs.
AB  - Pancreatic enzymes, such as trypsin and lipase, are essential for the digestion
      of dietary components in the small intestine. Measurement of both enzymes in
      jejunal fluid and fecal specimens from dogs has not been reported and will be a
      prelude for further investigations. Therefore, the aim of the study was to
      validate radioimmunoassays (RIAs) for the measurement of canine trypsin-like
      immunoreactivity (cTLI) and pancreatic lipase immunoreactivity (cPLI) in jejunal
      fluid and fecal specimens from dogs. Jejunal fluid and fecal specimens were
      collected from five healthy Beagles. A commercial (125)I-RIA was used for
      measuring cTLI concentrations and an in-house (125)I-RIA was modified for the
      quantification of cPLI in jejunal fluid and fecal specimens. Both RIAs were
      analytically validated for canine jejunal fluid and fecal specimens by
      determining dilutional parallelism, spiking recovery, and intra- and inter-assay
      variability. For both cTLI and cPLI in jejunal fluid, observed-to-expected ratios
      for dilutional parallelism and spiking recovery ranged from >=77.0% to ?115.3%
      and >=79.0% to <= 120.0%, respectively, and from >=87.2% to <= 118.5% and >=74.6%
      to <= 116.1%, respectively, for fecal specimens. Intra- and inter-assay
      coefficients of variation (%CV) for both cTLI and cPLI in jejunal fluid were <=
      7.6% and <= 10.0%, respectively, and were <= 10.8% and <= 9.0%, respectively, for
      fecal specimens. Both RIAs were demonstrated to be linear, accurate, precise, and
      reproducible for use with jejunal fluid and fecal specimens from dogs. These
      results are important for the investigation of pancreatic enzyme concentrations
      in the gastrointestinal lumen in response to changes in dietary components.

PMID- 23953599
TI  - Re: Sanoj Punnen, Matthew R. Cooperberg, Anthony V. D'Amico, et al. Management of
      biochemical recurrence after primary treatment of prostate cancer: a systematic
      review of the literature. Eur Urol. In press.
      http://dx.doi.org/10.1016/j.eururo.2013.05.025: Re: Firas Abdollah, Nazareno
      Suardi, Cesare Cozzarini, et al. Selecting the optimal candidate for adjuvant
      radiotherapy after radical prostatectomy for prostate cancer: a long-term
      survival analysis. Eur Urol 2013;63:998-1008.

PMID- 23953600
TI  - Timing of renal replacement therapy: is it when or how much?

PMID- 23953601
TI  - [Validation of segmentation techniques for positron emission tomography using ex
      vivo images of oncological surgical specimens].
AB  - OBJECTIVE: To design a novel ex-vivo acquisition technique to establish a common
      framework to validate different segmentation techniques for oncological PET
      images. To evaluate several automatic segmentation algorithms on this set of
      images. MATERIAL AND METHODS: In 15 patients with cancer, ex-vivo PET studies of
      surgical specimens removed during surgery were performed after injection of (18)F
      FDG. Images were acquired in two scanners: a clinical PET/CT and a high
      resolution PET scanner. Real tumor volume was determined in each patient, and a
      reference image was generated for segmentation of each tumor. Images were
      segmented with 12 automatic algorithms and with a standard method for PET
      (relative threshold at 42%) and results were evaluated by quantitative
      parameters. RESULTS: It has been possible to demonstrate by segmentation of PET
      images of surgical specimens that on high resolution PET images, 8 out of 12
      evaluated segmentation techniques outperformed the standard method, whose value
      is 42%. However, none of the algorithms outperformed the standard method when
      applied on images from the clinical PET/CT. Due to the great interest of this set
      of PET images, all studies have been published on the Internet in order to
      provide a common framework for validation and comparison of different
      segmentation techniques. CONCLUSIONS: We have proposed a novel technique to
      validate segmentation techniques for oncological PET images, acquiring ex-vivo
      PET studies of surgical specimens. We have demonstrated the usefulness of this
      set of PET images by evaluating several automatic segmentation algorithms.

PMID- 23953602
TI  - Circulating concentrations of GLP-1 are associated with coronary atherosclerosis
      in humans.
AB  - BACKGROUND: GLP-1 is an incretine hormone which gets secreted from intestinal L
      cells in response to nutritional stimuli leading to pancreatic insulin secretion
      and suppression of glucagon release. GLP-1 further inhibits gastric motility and
      reduces appetite which in conjunction improves postprandial glucose metabolism.
      Additional vasoprotective effects have been described for GLP-1 in experimental
      models. Despite these vasoprotective actions, associations between endogenous
      levels of GLP-1 and cardiovascular disease have yet not been investigated in
      humans which was the aim of the present study. METHODS: GLP-1 serum levels were
      assessed in a cohort of 303 patients receiving coronary CT-angiography due to
      typical or atypical chest pain. RESULTS: GLP-1 was found to be positively
      associated with total coronary plaque burden in a fully adjusted model containing
      age, sex, BMI, hypertension, diabetes mellitus, smoking, triglycerides, LDL-C
      (low density lipoprotein cholesterol), hsCRP (high-sensitive C-reactive protein),
      and eGFR (estimated glomerular filtration rate) (OR: 2.53 (95% CI: 1.12 - 6.08; p
      = 0.03). CONCLUSION: Circulating GLP-1 was found to be positivity associated with
      coronary atherosclerosis in humans. The clinical relevance of this observation
      needs further investigations.

PMID- 23953603
TI  - Pediatric genital injury: an analysis of the National Electronic Injury
      Surveillance System.
AB  - OBJECTIVE: To describe the characteristics of pediatric genital injuries
      presenting to United States emergency departments (EDs). METHODS: A retrospective
      cohort study utilizing the U.S. Consumer Product Safety Commission (CPSC)
      National Electronic Injury Surveillance System (NEISS) from 1991-2010 to evaluate
      pediatric genital injuries was performed. RESULTS: Pediatric genital injuries
      represented 0.6% of all pediatric injuries with the incidence of injuries rising
      through the period studied, 1991-2010. The mean age at injury was 7.1 years old
      and was distributed 56.6% girls and 43.4% boys. A total of 43.3% had lacerations
      and 42.2% had contusions/abrasions. The majority of injuries occurred at home
      (65.9%), and the majority of patients (94.7%) were treated and released from the
      hospital. The most common consumer products associated with pediatric genital
      trauma were: bicycles (14.7% of all pediatric genital injuries), bathtubs (5.8%),
      daywear (5.6%), monkey bars (5.4%), and toilets (4.0%). CONCLUSION: Although
      pediatric genital injuries represent a small proportion of overall injuries
      presenting to the emergency department, genital injuries continue to rise despite
      public health measures targeted to decrease childhood injury. Our results can be
      used to guide further prevention strategies for pediatric genital injury.

PMID- 23953604
TI  - The association between metabolic syndrome and the National Institutes of Health
      Chronic Prostatitis Symptom Index: results from 1673 men in China.
AB  - OBJECTIVE: To investigate the association between metabolic syndrome (MetS) and
      the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) in
      a population-based sample of Chinese men. METHODS: From October 2010 to July
      2011, 1896 men, aged between 20 and 50 years, residing in Shijingshan district of
      Beijing, China, were selected to participate in the Male Reproductive Health
      Program (a random cross-sectional survey). The Chinese version of the NIH-CPSI
      questionnaire was used to identify men with prostatitis-like symptoms. The
      presence of MetS was determined according to the 2005 National Cholesterol
      Education Program-Adult Treatment Panel III criteria for Asian Americans.
      RESULTS: Complete data were available for 1673 men. The major domains of NIH-CPSI
      scores were significantly different among different body mass index (BMI) groups
      (P <.05). No significant differences were identified in the incidence of
      prostatitis-like symptoms or each NIH-CPSI scores between patients with MetS and
      those without MetS. When the age and BMI were adjusted, there was no significant
      correlation between the components of MetS and each NIH-CPSI scores. CONCLUSION:
      There was no significant correlation between MetS or components of MetS and
      chronic prostatitis/chronic pelvic pain syndrome. Age and BMI were identified as
      a risk factor for chronic prostatitis/chronic pelvic pain syndrome. Further
      studies are necessary to confirm our results.

PMID- 23953605
TI  - Clinical efficacy and safety of imidafenacin as add-on treatment for persistent
      overactive bladder symptoms despite alpha-blocker treatment in patients with BPH:
      the ADDITION study.
AB  - OBJECTIVE: To evaluate the effects of add-on treatment with an anticholinergic
      (imidafenacin) on persistent overactive bladder (OAB) symptoms despite alpha
      blocker (tamsulosin) treatment in patients with benign prostatic hyperplasia
      (BPH). METHODS: Patients with BPH >=50 years old, with urinary urgency at least
      once per week and total OAB symptom score (OABSS) >=3 points after >=8-week
      treatment with tamsulosin were enrolled in a multicenter, open-label study (not
      double-blinded). Patients were randomized to receive tamsulosin (0.2 mg/day)
      alone or tamsulosin (0.2 mg/day) + imidafenacin (0.1 mg 2 times a day). Primary
      endpoint was 12-week change in OABSS; secondary endpoints were changes in OABSS,
      International Prostate Symptom Score (IPSS), micturition time chart (MTC), hours
      of undisturbed sleep (HUS), and quality of life (IPSS-QOL and BPH impact index
      [BII]). For statistical analysis, a mixed-effects model and t test were used.
      RESULTS: In total, 308 men were enrolled. The change from baseline to 12 weeks in
      total OABSS was significantly greater with add-on imidafenacin than tamsulosin
      alone (2.11, 95% confidence interval [CI] 1.47-2.74, P <.0001). Improvements in
      frequencies of daytime urination, nighttime urination, urinary urgency, urgency
      incontinence, IPSS, HUS, IPSS-QOL, and BII, were significantly greater from 4
      weeks through 12 weeks in the imidafenacin group. Between-group difference in
      postvoid residual volume at 12 weeks was not significant (-1.74 mL, 95% CI -8.19
      to 4.72), and no events of urinary retention were reported. CONCLUSION: Combined
      tamsulosin and imidafenacin treatment is effective and safe in patients with BPH
      with persistent OAB symptoms after tamsulosin monotherapy. Furthermore the
      combination treatment improved the QOL in BPH patients with OAB.

PMID- 23953607
TI  - Editorial comment.

PMID- 23953608
TI  - Continuous-wave infrared subsurface optical stimulation of the rat prostate
      cavernous nerves using a 1490-nm diode laser.
AB  - OBJECTIVE: To optimize the infrared laser wavelength and optical nerve
      stimulation (ONS) parameters for both deep and rapid subsurface cavernous nerve
      (CN) stimulation in a rat model, in vivo. MATERIALS AND METHODS: A 150-mW, 1490
      nm diode laser providing an optical penetration depth (OPD) of 518 MUm in water
      was operated in continuous-wave mode during stimulation of the CNs in 8 rats for
      15 seconds irradiation time through a custom-built, single-mode fiber optic probe
      capable of producing a collimated, 1-mm diameter laser beam. Successful ONS was
      judged by an intracavernous pressure response in the rat penis. Subsurface ONS at
      1490 nm was also compared with previous studies using 1455 nm and 1550 nm near
      infrared diode laser wavelengths. RESULTS: Subsurface ONS of the rat CN was
      successful through fascia layers with a thickness up to 380 MUm using an incident
      laser power of ~50 mW. Intracavernous pressure response times as short as 4.6 +/-
      0.2 seconds were recorded using higher laser powers below the nerve damage
      threshold. CONCLUSION: The 1490-nm diode laser represents a compact, low cost,
      high power, and high quality infrared light source for use in ONS. This
      wavelength provides deeper penetration than 1455-nm diode laser and more rapid
      and efficient nerve stimulation than 1550-nm diode laser.

PMID- 23953609
TI  - Different cystic fibrosis transmembrane conductance regulator mutations in
      Chinese men with congenital bilateral absence of vas deferens and other acquired
      obstructive azoospermia.
AB  - OBJECTIVE: To investigate cystic fibrosis transmembrane conductance regulator
      (CFTR) gene in Chinese men with congenital bilateral absence of vas deferens
      (CBAVD) and other obstructive azoospermia. MATERIALS AND METHODS: Four hundred
      one patients with obstructive azoospermia were included. Patients were grouped as
      158 with CBAVD and 243 with other acquired obstructive azoospermia. Another 200
      fertile men were used as controls. Genomic deoxyribonucleic acid was isolated
      from peripheral blood lymphocytes for all men. The exon 10 and 11 CFTR genes were
      amplified and sequenced. The frequency of CFTR gene mutations was compared among
      3 groups. RESULTS: Six heterozygous mutations (+/-), I556V, M469V, E527N,
      F508del, S485C, and I558S, were found in 30 patients, and 1 homozygous mutation
      (+/+), I556V, was found in 1 patient. The overall frequency of CFTR mutations was
      31 of 401 (7.7%). Of these mutations, I556V was the most common type with 24 of
      31 (77.4%). In CBAVD group, 20 of 158 patients were identified with 6 different
      heterozygous mutations (I556V, M469V, E527N, F508del, S485C, and I558S) and 1
      homozygous mutation (I556V). The rate of CFTR mutations was 12.7%. In acquired
      obstructive group, 11 of 243 patients were identified with 2 different
      heterozygous mutations, I556V and M469V; the rate of mutations was 4.5%. No CFTR
      mutations were identified in controls. There was significant difference among 3
      groups (P = .000). The frequency of CFTR mutations in CBAVD is 2-fold higher than
      in other acquired obstructive group. CONCLUSION: Different CFTR mutations are
      observed in Chinese patients with CBAVD. I556V is the major common type of CFTR
      mutations in Chinese patients with CBAVD.

PMID- 23953610
TI  - The impact of OAB on physical activity in the United States: results from OAB
      POLL.
AB  - OBJECTIVE: To provide data on physical activity among those with and without
      overactive bladder (OAB) in a large, ethnically diverse U.S. sample. METHODS: A
      cross-sectional survey was conducted via the Internet among 10,000 men and women
      aged 18-70 (2000 African Americans, 2000 Hispanics, and 6000 whites) using the
      lower urinary tract symptoms (LUTS) tool and questions from the 2007-2008
      National Health and Nutrition Examination Survey (NHANES). OAB cases and those
      with no/minimal symptoms (NMS) were compared on federal guidelines of indices of
      physical activity: 2008 guidelines and 2010 Healthy People. Descriptive
      statistics were used to evaluate differences between OAB and NMS. Logistic
      regressions examined the impact of OAB on physical activity. RESULTS: Response
      rate, 57%; 818 men and 1505 women with OAB, and 1857 men and 1615 women with NMS.
      Respondents with other LUTS were excluded from this analysis (2302 men and 1904
      women). Those with OAB were significantly less likely to report moderate and
      vigorous physical activities in their leisure time and to satisfy recommended
      physical activity levels compared to those with NMS. Symptoms of OAB (men and
      women: urgency and urinary frequency; women: urinary urge incontinence) were
      associated with limitations in physical activity in the logistic regressions.
      CONCLUSION: This study benchmarks physical activity levels among people with OAB.
      Men and women with OAB were significantly less likely to achieve recommended
      physical activity levels than people with NMS. More research is needed to further
      evaluate how OAB affects physical activity and health status and to determine
      causal relationships.

PMID- 23953611
TI  - Effects of eluent temperature and elution bandwidth on detection response for
      aerosol-based detectors.
AB  - Aerosol detectors provide generally uniform response for most analytes,
      independent of their optical properties, and have the advantage of being
      compatible with elevated temperature mobile phases. Therefore, aerosol detectors
      present an attractive detection alternative for high temperature liquid
      chromatography (HTLC) separations. The present study has investigated the effects
      of HTLC conditions using aqueous mobile phases on the detection response of an
      evaporative light-scattering detector (ELSD) and a corona-charged aerosol
      detector (C-CAD). The response of the ELSD was increased up to 5-fold by
      increasing the separation temperature from 30 degrees C to 180 degrees C. The C
      CAD showed much smaller increases in response under the same conditions. This
      increase in response was found not to result from the increased temperature for
      the mobile phase but rather from compression of the elution bandwidth at elevated
      temperature. The effect of bandwidth on detector response was confirmed using
      flow-injection studies in which the same amount of analyte was introduced into
      the detector at varying bandwidths. Furthermore, it is shown that a temperature
      gradient can be used to counteract the effects of varying bandwidths associated
      with isocratic-isothermal separations, with relatively constant bandwidth and
      detector response being observed with appropriate temperature gradients. This
      study demonstrates the necessity to consider the elution bandwidth in HTLC
      aerosol detector analysis.

PMID- 23953612
TI  - Electromembrane extraction from aqueous samples containing polar organic
      solvents.
AB  - Electromembrane extraction (EME) was performed from aqueous samples and from
      aqueous samples containing methanol, ethanol, dimethyl sulfoxide, and
      acetonitrile. The basic drugs pethidine, haloperidol, nortriptyline, methadone
      and loperamide were used as model analytes. Reversed phase (C18) HPLC with UV
      (235 nm) and MS detection was used for analysis of the samples. With no organic
      solvent in the sample, maximum recoveries were obtained after 5-10 min. The
      maximum recoveries ranged between 83 and 95%. With 50% (v/v) methanol, ethanol,
      or dimethyl sulfoxide in the sample, recoveries were comparable to those from an
      aqueous sample, but the time required reaching maximum recovery increased to 15
      25 min. With 2-nitrophenyl octyl ether (NPOE) as the supported liquid membrane
      (SLM), a stable EME system was obtained for 50% (v/v) methanol, 50% (v/v)
      ethanol, or 75% (v/v) dimethyl sulfoxide in the sample solution. On the other
      hand, the EME system was unstable with acetonitrile in the sample, as this
      solvent partly dissolved the SLM. In addition, acetonitrile migrated through the
      SLM and caused a volume expansion of the acceptor solution. Other SLMs were also
      tested (ethyl nitrobenzene, isopropyl nitrobenzene, and dodecyl nitrobenzene),
      but were inferior to NPOE. As a practical example, EME on dried blood spot
      extracts (80% methanol) were tested, and proved highly successful. These
      observations showed that EME can be an effective way of preparing aqueous samples
      containing substantial amounts of an organic solvent.

PMID- 23953613
TI  - A new method for the determination of biological oxygen demand in domestic
      wastewater by headspace gas chromatography.
AB  - A headspace gas chromatographic method (HS-GC) has been developed for the
      determination of biological oxygen demand (BOD) in the water samples from
      domestic wastewater treatment plants. The method is based on measuring the
      remaining oxygen in the headspace of the sample (that has been seeded with
      microorganisms) in a closed container after a period of incubation. The relative
      standard deviation of the method in replicate testing was <4.9%. Further, the
      results differed by less than 6% when compared with the widely used reference
      method (the ISO standard) for determining BOD5. The limit of quantification in
      BODn testing was about 1.8 mg/L. The new method is simple and suitable for use in
      the batch sample testing for BODn measurement.

PMID- 23953614
TI  - Comprehensive two-dimensional gas chromatography with a multi-capillary second
      dimension: a new column-set format for simultaneous optimum linear velocity
      operation.
AB  - Comprehensive two-dimensional gas chromatography (GC*GC) suffers from the
      impossibility to operate both dimensions at their optimum carrier gas velocity at
      the same time due to the different inner diameters of the columns typically
      employed. The use of multiple parallel capillary columns in the second dimension
      (GC*multi-GC) is studied as a means to achieve simultaneous optimum-velocity
      operation. A programme written in Microsoft Excel((r)) was developed to calculate
      the efficiency of the two dimensions in GC*multi-GC for different numbers of
      columns in the second dimension. With the aid of this programme the appropriate
      number of columns was selected. Columns with maximum repeatability were
      specifically manufactured to grand suitable performance, i.e. to avoid band
      broadening effects caused by inter-column variations. 1D-GC experiments were
      carried out on the columns separately and combined in parallel. The performance
      of the parallel column set was consistent with that of the individual columns,
      with over 9100 plates generated (approximately 10,000 plates/m). A GC*multi-GC
      set-up was successfully installed. Model experiments proved the possibility to
      operate both dimensions at their optimum linear velocity simultaneously. The
      suitability of the novel second dimension column format to perform
      multidimensional separations was also shown for a number of selected
      applications.

PMID- 23953615
TI  - Rational design and chromatographic evaluation of histamine imprinted polymers
      optimised for solid-phase extraction of wine samples.
AB  - This article reports on the computational design, development and application of
      a molecularly imprinted polymer (MIP) with specific affinity towards histamine.
      Computational modelling was used to screen a monomer library in order to select
      the monomers able to form the strongest complex with the target analyte. These
      were subsequently used for MIP synthesis by radical polymerisation initiated by
      UV. MIPs were then evaluated by liquid chromatography and solid phase extraction
      (SPE) and best MIP behaviour was observed when itaconic acid was used as
      functional monomer. Finally, after optimisation of the polymer composition, MIPs
      were used as adsorbents for SPE and clean-up of histamine in wine samples. The
      proposed histamine extraction method with the MIP-SPE cartridge was found to be
      reproducible (<5% RSD) and accurate (93-99% recovery) and provided clear wine
      extracts. The described methodology is simple and fast and is suitable for the
      selective histamine extraction and its subsequent quantification by HPLC-DAD from
      complex matrices such as wine samples. 

PMID- 23953616
TI  - Determination of the distribution constants of aromatic compounds and steroids in
      biphasic micellar phosphonium ionic liquid/aqueous buffer systems by capillary
      electrokinetic chromatography.
AB  - The distribution constants of some analytes, closely connected to the
      petrochemical industry, between an aqueous phase and a phosphonium ionic liquid
      phase, were determined by ionic liquid micellar electrokinetic chromatography
      (MEKC). The phosphonium ionic liquids studied were the water-soluble
      tributyl(tetradecyl)phosphonium with chloride or acetate as the counter ion. The
      retention factors were calculated and used for determination of the distribution
      constants. For calculating the retention factors the electrophoretic mobilities
      of the ionic liquids were required, thus, we adopted the iterative process, based
      on a homologous series of alkyl benzoates. Calculation of the distribution
      constants required information on the phase-ratio of the systems. For this the
      critical micelle concentrations (CMC) of the ionic liquids were needed. The CMCs
      were calculated using a method based on PeakMaster simulations, using the
      electrophoretic mobilities of system peaks. The resulting distribution constants
      for the neutral analytes between the ionic liquid and the aqueous (buffer) phase
      were compared with octanol-water partitioning coefficients. The results indicate
      that there are other factors affecting the distribution of analytes between
      phases, than just simple hydrophobic interactions. 

PMID- 23953617
TI  - Surface excess isotherms of organic solvent mixtures in a system made of liquid
      carbon dioxide and a silicagel surface.
AB  - The surface excess isotherms of methanol, ethanol, 2-propanol and acetonitrile
      from liquid carbon dioxide on a silica adsorbent were measured, using the minor
      disturbance method. The minor disturbance peaks - or system peaks - of each
      organic modifier were recorded using UV-detection in the whole composition range
      of the organic/liquid carbon dioxide mixtures, the whole composition range was
      completed by injecting the modifiers into pure liquid carbon dioxide as well. The
      excess isotherms were calculated based on the retention of the organic solvent
      signals. Our results show an enrichment of the organic modifier at the adsorbent
      surface. The alcohols show multilayer adsorption with an extremely high retention
      on the silica surface while acetonitrile shows weaker interactions and only a
      slight trend toward the formation of a multilayer above the surface. 

PMID- 23953619
TI  - Liquid crystal-based molecularly imprinted nanoparticles with low crosslinking
      for capillary electrochromatography.
AB  - In this work, molecularly imprinted polymer (MIP) nanoparticles were prepared at
      a low level of crosslinking in the presence of liquid crystalline monomer as
      physical crosslinker to replace the most of chemical crosslinker. The imprinted
      nanoparticles against d-zopiclone were synthesized by precipitation
      polymerization using a mixture of methacrylic acid, ethylene glycol
      dimethacrylate, and liquid crystalline monomers. The resulting d-zopiclone
      imprinted nanoparticles were evaluated in capillary electrochromatography by
      partial filling technique. The resolution of enantiomer separation achieved on
      the d-zopiclone-imprinted nanoparticles was up to 3.29 and the column efficiency
      of zopiclone enantiomer (up to 66,900 plates/m) with good peak symmetry was
      obtained. The imprinted nanoparticles prepared in the presence of liquid
      crystalline monomer can retain affinity and specificity for template even when
      prepared with a level of cross-linker as low as 5%. 

PMID- 23953618
TI  - Robust analysis of the hydrophobic basic analytes loratadine and desloratadine in
      pharmaceutical preparations and biological fluids by sweeping-cyclodextrin
      modified micellar electrokinetic chromatography.
AB  - The analysis of hydrophobic basic analytes by micellar electrokinetic
      chromatography (MEKC) is usually challenging because of the tendency of these
      analytes to be adsorbed onto the inner capillary wall in addition to the
      difficulty to separate these compounds as they exhibit extremely high retention
      factors. A robust and reliable method for the simultaneous determination of
      loratadine (LOR) and its major metabolite desloratadine (DSL) is developed based
      on cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) with
      acidic sample matrix and basic background electrolyte (BGE). The influence of the
      sample matrix on the reachable focusing efficiency is studied. It is shown that
      the application of a low pH sample solution mitigates problems associated with
      the low solubility of the hydrophobic basic analytes in aqueous solution while
      having advantages with regard to on-line focusing. Moreover, the use of a basic
      BGE reduces the adsorption of these analytes in the separation compartment. The
      separation of the studied analytes is achieved in less than 7min using a BGE
      consisting of 10mmolL(-1) disodium tetraborate buffer, pH 9.30 containing
      40mmolL(-1) SDS and 20mmolL(-1) hydroxypropyl-beta-CD while the sample solution
      is composed of 10mmolL(-1) phosphoric acid, pH 2.15. A full validation study of
      the developed method based on the pharmacopeial guidelines is performed. The
      method is successfully applied to the analysis of the studied drugs in tablets
      without interference of tablet additives as well as the analysis of spiked human
      urine without any sample pretreatment. Furthermore, DSL can be detected as an
      impurity in LOR bulk powder at the stated pharmacopeial limit (0.1%, w/w). The
      selectivity of the developed method allows the analysis of LOR and DSL in
      combination with the co-formulated drug pseudoephedrine. It is shown that in CD
      MEKC with basic BGE, solute-wall interactions are effectively suppressed allowing
      the development of efficient and precise methods for the determination of
      hydrophobic basic analytes, whereas the use of a low pH sample solution has a
      positive impact on the attainable sweeping efficiency without compromising peak
      shape and resolution. 

PMID- 23953620
TI  - Kinetic evaluation of new generation of column packed with 1.3 MUm core-shell
      particles.
AB  - The goal of this study was to critically evaluate a new generation of columns
      packed with 1.3 MUm core-shell particles. The practical possibilities and
      limitations of this column technology were assessed and performance was compared
      with other reference columns packed with 1.7, 2.6 and 5 MUm core-shell particles.
      The column efficiency achieved with 1.3 MUm core-shell particles was indeed
      impressive, Hmin value of only 1.95 MUm was achieved, this would correspond to an
      efficiency of more than 500,000 plates/m. The separation impedance of this column
      was particularly low, Emin=2000, mostly due to a reduced plate height, h of 1.50.
      Comparing the kinetic performance of 1.3 MUm core-shell particles to that of
      other particle dimensions tested in this study revealed that the 1.3 MUm material
      could provide systematically the shortest analysis time in a range of below
      30,000 theoretical plates (N<30,000).Despite its excellent chromatographic
      performance, it was evident that this column suffers from the limitations of
      current instrumentation in terms of upper pressure limit and extra-column band
      broadening: (1) even at 1,200 bar, it was not possible to reach an optimal linear
      velocity showing minimal plate height value, due to the low permeability of this
      column (Kv=1.7*10(-11)cm(2)), and (2) for these short narrow bore columns packed
      with 1.3 MUm core shell particles, which is mandatory for performing fast
      analysis and preventing the influence of frictional heat on column performance in
      UHPLC, it was observed that the extra-column band broadening could have a major
      impact on the apparent kinetic performance. In the present work, significant
      plate count loss was noticed for retention factors of less than 5, even with the
      best system on the market (sigma(2)ec=2 MUL(2)).

PMID- 23953621
TI  - Possible association of Toll-like receptor 9 polymorphisms with cytokine levels
      and posttraumatic symptoms in individuals with various types of orthopaedic
      trauma: early findings.
AB  - BACKGROUND: Although TLR9 polymorphisms may be associated with cytokine
      dysregulation, its role in regulation of cytokines due to bodily trauma or in
      relation to acute stress symptoms or posttraumatic stress symptoms (ASS/PTS) has
      not been evaluated. AIMS: To assess serum cytokine levels and levels of ASS and
      PTS in relation to four common TLR9 single-nucleotide polymorphisms (SNPs) in
      individuals with various types of orthopaedic trauma. METHODS: Forty-eight
      accident-injured individuals, aged 20-60 years were studied. Serum cytokine
      levels and TLR9 SNPS (1486T/C, 1237T/C, 1174G/A and 2848G/A) were assessed
      together with intensity of ASS and PTS symptoms. RESULTS: Statistically
      significant higher serum levels of IL-12 and IL-1beta (p<.05) were found in
      individuals heterozygous for TLR9-1237 (TC) than in individuals expressing the
      most common TLR9-1237 type (TT), while differences in levels of IL-6 were not
      significant. Also, marginally significant levels of IL-6 were found in
      individuals expressing the common TLR9-1174 (GG) compared with individuals
      homozygous (AA) or heterozygous (GA) for this SNP. They also had non-significant
      higher intensity of ASS symptoms. A trend of higher PTS levels in individuals
      expressing the most common type TLR9-1174 (GG) was found, contrary to homozygous
      (AA) and heterozygous individuals (GA). CONCLUSIONS: The results of this pilot
      study suggest that accident-injured individuals with certain TLR9 polymorphisms
      express higher levels of pro-inflammatory cytokines (IL-1beta, IL-6 and IL-12).
      The associations of TLR9 SNPSs with increased risk of ASS or PTS should be
      further studied in larger groups of such patients.

PMID- 23953622
TI  - Variability in the response to non-steroidal anti-inflammatory drugs: mechanisms
      and perspectives.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are a chemically heterogeneous
      group of compounds that provide unmistakable and significant health benefits in
      the treatment of pain and inflammation. They include traditional NSAIDs
      (tNSAIDs), which act by inhibiting both cyclooxygenase (COX)-1 and COX-2 and
      selective COX-2 inhibitors (coxibs). The development of biomarkers predictive of
      the impact of NSAIDs on COX-1 and COX-2 activities in vitro, ex vivo and in vivo
      has been essential to read out the clinical consequences of selective and non
      selective inhibition of COX isozymes in human beings. The analgesic and anti
      inflammatory effects of NSAIDs are COX-2-dependent effects, unrelated to COX-2
      selectivity. The intensity and duration of these effects are influenced by dose
      and half-life of the NSAID. However, the inhibition of COX-1 in cells of the
      gastrointestinal (GI) system and COX-2 in vascular cells translates into
      increased risk of serious GI adverse events and atherothrombosis and
      hypertension, respectively. The COX-2 selectivity of NSAIDs can predict, at least
      in part, the GI toxicity. In contrast, the CV effects are largely COX-2-dependent
      effects, unrelated to COX-2 selectivity but are dose dependent. The reduction in
      the dose is recommended and presumably will limit the number of patients exposed
      to a CV or a GI hazard by NSAIDs and coxibs. It will not, however, eliminate the
      risk on an individual level because there is a marked variability in how
      different people react to these drugs, based on their genetic background. The
      challenge of the next future will be to develop biomarkers useful to identify the
      individuals who react abnormally to COX inhibition. 

PMID- 23953623
TI  - Cardiac arrest and arterial air emboli associated with subcutaneous emphysema and
      pneumothorax in a French bulldog.

PMID- 23953624
TI  - A HER2-targeted RNA aptamer molecule labeled with 99mTc for single-photon imaging
      in malignant tumors.
AB  - A modified RNA aptamer with HER2-specific binding was conjugated to hynic and
      labeled with (99m)Tc, for potential use as a radiopharmaceutical for diagnostic
      imaging of ovarian cancer cells (SKOV-3) with high HER2 expression. The aptamer
      was radiolabeled with (99m)Tc by using hynic as the chelator and tricine as the
      co-ligand. Stability testing of the radioconjugated aptamer was performed via
      ITLC and SDS-PAGE in normal saline and serum. The aptamer-radionuclide conjugate
      was evaluated for cellular HER2-specific binding, saturation affinity, and
      cellular internalization in SKOV-3 and MCF-7 cells, and its biodistribution
      properties were assessed in normal and SKOV-3 tumor-bearing mice. Radiolabeling
      of the aptamer was achieved with high yield and radiochemical purity, and the
      (99m)Tc-hynic-RNA aptamer was highly stable in normal saline and serum. Cellular
      experiments showed specific binding of the aptamer to the HER2 receptor with a
      dissociation constant of 27 nM. Rapid blood clearance was observed after
      injection of the (99m)Tc-hynic-RNA aptamer, and the main excretion route was via
      the hepatobilary system. While the radioconjugated aptamer bound specifically to
      the HER2 receptor on cells in vitro, it did not show any significant tumor-to
      blood or tumor-to-muscle ratios in mice. Modifications to radiolabeled aptamer
      will require improving its pharmacokinetic properties and tumor uptake in vivo.

PMID- 23953625
TI  - [A child with sepsis-associated encephalopathy].
AB  - Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction due to a
      systemic response to infection. We report the case of a 4-year-old girl with
      fever and vomiting for 48h, brought to the university hospital of Grenoble
      because of vigilance disorders, loss of verbal fluency, and a cerebellar
      syndrome. She had a biological infectious syndrome. Infectious encephalitis was
      suggested first, but the cerebral scan and the lumbar punction were normal.
      Magnetic resonance imaging (MRI) showed a diffuse brain edema with extended
      involvement of cortical and basal ganglia. The electroencephalogram was globally
      slow. The infectious syndrome was explained by perforated appendicitis with
      peritonitis, treated by surgery and antibiotic therapy. Other infectious
      explorations were negative. No metabolic or autoimmune diseases were found.
      Hence, our final diagnosis was sepsis-associated encephalopathy. After 1 year of
      follow-up care, her clinical exam, MRI, and EEG were normal. Sepsis-associated
      encephalopathy has been increasingly described in the adult population, but until
      today only three pediatric cases have been published. It is diagnosed when the
      patient has a severe infectious syndrome associated with neurologic symptoms,
      mostly vigilance or consciousness disorders, no signs of shock, and only when
      other potential reasons have been ruled out. The MRI shows non-specific diffuse
      lesions with vasogenic edema on the subcortical substance or on the basal ganglia
      and the thalami. The electroencephalogram is slowed down on the whole. The main
      differential diagnoses are infectious encephalitis, acute disseminated
      encephalomyelitis, and cerebral vasculitis. Posterior reversible encephalopathy
      syndrome is an MRI diagnosis that presents characteristics similar to SAE. In the
      future, it could be discovered that it is the same physiopathology. At the
      moment, we only treat the symptoms and the causative infection. Most of the time,
      patients have neurologic sequelae that affect their verbal fluency. It can
      persist from a few months up to 6yrs. Although quite slow, the neurologic
      progression is good. The mechanisms are studied and there are hopes for specific
      treatments. The main explanation seems to be immune with alterations of the blood
      brain barrier. Cytokines and activated leukocytes may attack the cerebral
      substance. 

PMID- 23953626
TI  - [Treatment of acute gastroenteritis in private practice: a survey of 641
      pediatricians].
AB  - Acute gastroenteritis (AGE) is a very common reason for pediatric consultations.
      Various expert committees have issued guidelines for its management, based on
      systematic use of an oral rehydration solution (ORS), early appropriate nutrition
      (most recent previous diet), and avoiding routine treatment with medication. The
      aim of the study was to assess the application of these guidelines by
      pediatricians in outpatient practice for mild to moderate AGE. A secondary
      objective was to question pediatricians about their practices for vaccination
      against rotavirus. METHODS: In June 2012, e-mail requests were sent to 1187
      pediatricians in private practice, asking them to complete an anonymous
      questionnaire online at the website of the French Association of Pediatricians in
      Outpatient Practice. RESULTS: A total of 641 (54%) responses could be analyzed.
      Nearly all the pediatricians recommended early resumption of nutrition after
      administration of ORS. Depending on the child's age, 16 to 23% reported they
      would recommend resuming feeding with lactose-free milk, and 80% would advise an
      antidiarrhea diet for children older than 6 months. The drugs prescribed most
      often were, in decreasing order, racecadotril (acetorphan), diosmectite, and
      probiotics. Although 90% of the pediatricians prescribed vaccination against
      rotavirus, 65% estimated that it was performed in more than half of all children.
      CONCLUSION: This study of the management of moderate acute gastroenteritis shows
      variable adhesion to guidelines by pediatricians treating outpatients. Although
      ORS, maintenance of breastfeeding, and early nutrition after ORS are now widely
      applied, the type of nutrition recommended often failed to meet guidelines. Drug
      prescription is still too frequent. Anti-rotavirus vaccine is prescribed often
      but is administered much less frequently.

PMID- 23953627
TI  - [Unusual presentation of a severe Mycoplasma pneumoniae infection: report of 2
      cases].
AB  - Mycoplasma pneumonia is responsible for multisystemic infection. Pulmonary
      symptoms are most common in children. We describe herein two unusual severe forms
      of M. pneumoniae infection without initial pulmonary symptoms. The first case is
      an 8-month-old boy who was hospitalized in the pediatric intensive care unit with
      severe sepsis. There were no initial pulmonary symptoms, nor obvious clinical
      infection. Initial blood tests and x-ray did not aid the diagnosis. The blood
      tests came back positive for M. pneumonia. Pulmonary symptoms eventually appeared
      24h later, and there was a pneumonia outbreak on the chest radiograph. The boy
      was given josamycin and improved quickly. The second case concerns an 8-year-old
      child who was hospitalized in the pediatric intensive care unit with toxic shock.
      No clinical infectious origin was found. A broad-spectrum antibiotic therapy was
      started with ceftriaxone and josamycin. The M. pneumoniae blood test came back
      positive, which confirmed the diagnosis of septic shock in M. pneumoniae,
      requiring adjustment of the antibiotic therapy. Current guidelines for the choice
      of probabilistic antibiotic therapy in case of severe sepsis do not include the
      case of M. pneumoniae. The early initiation of antibiotic therapy plays a major
      role in the prognosis of these patients. It seems useful to search for M.
      pneumoniae in cases of severe atypical infections, particularly in the absence of
      pulmonary symptoms. 

PMID- 23953628
TI  - Outcome of treatment of implant-retained overdenture in patients with extreme
      mandibular bone resorption treated with bone grafts using a modified tent pole
      technique.
AB  - PURPOSE: To evaluate the outcome (prosthetic maintenance, survival of implants,
      patient satisfaction, and quality of life) of prosthetic treatment using an
      implant-retained overdenture and a modified tent pole procedure for severe
      mandibular resorption. MATERIAL AND METHODS: Seventeen edentulous patients (mean
      age, 68 yr; range, 54 to 77 yr) with severely resorbed mandibles were treated
      with autogenous bone grafts using a modified tent pole technique and implant
      overdentures. A bar was used to splint the implants and the final prostheses with
      implant connection were completed approximately 7 months after surgery. The mean
      follow-up time was 5 years (1.5 to 7.4 yr). Patients filled out the Oral Health
      Impact Profile-14 questionnaire concerning their oral health-related quality of
      life, and then panoramic radiographs were taken during clinical examination.
      RESULTS: The stability of the overdenture was good in 58.8% of cases and
      retention was good in 64.7%. The most usual prosthetic complication was loosening
      of the attachment component, which occurred in 7 cases (41.2%). The amount of
      plaque and bleeding was more remarkable on the lingual surface of the implants
      and less remarkable on the buccal surface. Pocket depth around the implants
      seemed to correspond to intraoral implantation. The radiographs depicted
      excellent grafted bone survival. The patients' oral health-related quality of
      life was found to be good after treatment. CONCLUSIONS: Implant placement with
      bone grafting using a modified tent pole technique enables the achievement of a
      good prosthetic solution and the rehabilitation of occlusion, thereby improving
      the functionality of the prostheses and quality of life.

PMID- 23953629
TI  - The role of housing characteristics in biomarkers: US NHANES, 2003-2006.

PMID- 23953631
TI  - Ethnic differences in childhood autonomic nervous system regulation.

PMID- 23953630
TI  - Percutaneous device closure of an aortopulmonary window in a small infant.

PMID- 23953632
TI  - Testosterone and acute stress are associated with fibrinogen and von Willebrand
      factor in African men: the SABPA study.
AB  - BACKGROUND: Low testosterone, acute and chronic stress and hypercoagulation are
      all associated with hypertension and hypertension-related diseases. The
      interaction between these factors and future risk for coronary artery disease in
      Africans has not been fully elucidated. In this study, associations of
      testosterone, acute cardiovascular and coagulation stress responses with
      fibrinogen and von Willebrand factor in African and Caucasian men in a South
      African cohort were investigated. METHODS: Cardiovascular variables were studied
      by means of beat-to-beat and ambulatory blood pressure monitoring. Fasting serum
      , salivary testosterone and citrate coagulation markers were obtained from venous
      blood samples. Acute mental stress responses were evoked with the Stroop test.
      RESULTS: The African group demonstrated a higher cardiovascular risk compared to
      Caucasian men with elevated blood pressure, low-grade inflammation, chronic
      hyperglycemia (HbA1c), lower testosterone levels, and elevated von Willebrand
      factor (VWF) and fibrinogen levels. Blunted testosterone acute mental stress
      responses were demonstrated in African males. In multiple regression analyses,
      higher circulating levels of fibrinogen and VWF in Africans were associated with
      a low T environment (R(2) 0.24-0.28; p<=0.01), but only circulating fibrinogen in
      Caucasians. Regarding endothelial function, a low testosterone environment and a
      profile of augmented alpha-adrenergic acute mental stress responses (diastolic
      BP, D-dimer and testosterone) were associated with circulating VWF levels in
      Africans (Adj R(2) 0.24; p<0.05). CONCLUSIONS: An interdependence between acute
      mental stress, salivary testosterone, D-dimer and vascular responses existed in
      African males in their association with circulating VWF but no interdependence of
      the independent variables occurred with fibrinogen levels.

PMID- 23953633
TI  - Long-term prognostic value of preprocedural adiponectin levels in patients
      undergoing percutaneous coronary intervention.

PMID- 23953634
TI  - Assessing the uncertainty in QUANTEC's dose-response relation of lung and spinal
      cord with a bootstrap analysis.
AB  - PURPOSE: To apply a statistical bootstrap analysis to assess the uncertainty in
      the dose-response relation for the endpoints pneumonitis and myelopathy reported
      in the QUANTEC review. METHODS AND MATERIALS: The bootstrap method assesses the
      uncertainty of the estimated population-based dose-response relation due to
      sample variability, which reflects the uncertainty due to limited numbers of
      patients in the studies. A large number of bootstrap replicates of the original
      incidence data were produced by random sampling with replacement. The analysis
      requires only the dose, the number of patients, and the number of occurrences of
      the studied endpoint, for each study. Two dose-response models, a Poisson-based
      model and the Lyman model, were fitted to each bootstrap replicate using maximum
      likelihood. RESULTS: The bootstrap analysis generates a family of curves
      representing the range of plausible dose-response relations, and the 95%
      bootstrap confidence intervals give an estimated upper and lower toxicity risk.
      The curve families for the 2 dose-response models overlap for doses included in
      the studies at hand but diverge beyond that, with the Lyman model suggesting a
      steeper slope. The resulting distributions of the model parameters indicate
      correlation and non-Gaussian distribution. For both data sets, the likelihood of
      the observed data was higher for the Lyman model in >90% of the bootstrap
      replicates. CONCLUSIONS: The bootstrap method provides a statistical analysis of
      the uncertainty in the estimated dose-response relation for myelopathy and
      pneumonitis. It suggests likely values of model parameter values, their
      confidence intervals, and how they interrelate for each model. Finally, it can be
      used to evaluate to what extent data supports one model over another. For both
      data sets considered here, the Lyman model was preferred over the Poisson-based
      model.

PMID- 23953635
TI  - Salvage/adjuvant brachytherapy after ophthalmic artery chemosurgery for
      intraocular retinoblastoma.
AB  - PURPOSE: To evaluate the efficacy and toxicity of brachytherapy after ophthalmic
      artery chemosurgery (OAC) for retinoblastoma. METHODS AND MATERIALS: This was a
      single-arm, retrospective study of 15 eyes in 15 patients treated with OAC
      followed by brachytherapy at (blinded institution) between May 1, 2006, and
      December 31, 2012, with a median 19 months' follow-up from plaque insertion.
      Outcome measurements included patient and ocular survival, visual function, and
      retinal toxicity measured by electroretinogram (ERG). RESULTS: Brachytherapy was
      used as adjuvant treatment in 2 eyes and as salvage therapy in 13 eyes of which
      12 had localized vitreous seeding. No patients developed metastasis or died of
      retinoblastoma. The Kaplan-Meier estimate of ocular survival was 79.4% (95%
      confidence interval 48.7%-92.8%) at 18 months. Three eyes were enucleated, and an
      additional 6 eyes developed out-of-target volume recurrences, which were
      controlled with additional treatments. Patients with an ocular complication had a
      mean interval between last OAC and plaque of 2.5 months (SD 2.3 months), which
      was statistically less (P=.045) than patients without ocular complication who had
      a mean interval between last OAC and plaque of 6.5 months (SD 4.4 months). ERG
      responses from pre- versus postplaque were unchanged or improved in more than
      half the eyes. CONCLUSIONS: Brachytherapy following OAC is effective, even in the
      presence of vitreous seeding; the majority of eyes maintained stable or improved
      retinal function following treatment, as assessed by ERG.

PMID- 23953636
TI  - Predictive parameters of CyberKnife fiducial-less (XSight Lung) applicability for
      treatment of early non-small cell lung cancer: a single-center experience.
AB  - PURPOSE: To determine which parameters allow for CyberKnife fiducial-less tumor
      tracking in stereotactic body radiation therapy (SBRT) for early-stage non-small
      cell lung cancer. METHODS AND MATERIALS: A total of 133 lung SBRT patients were
      preselected for direct soft-tissue tracking based on manufacturer recommendations
      (peripherally located tumors >=1.5 cm with a dense appearance) and staff
      experience. Patients underwent a tumor visualization test to verify adequate
      detection by the tracking system (orthogonal radiographs). An analysis of
      potential predictors of successful tumor tracking was conducted looking at: tumor
      stage, size, histology, tumor projection on the vertebral column or mediastinum,
      distance to the diaphragm, lung-to-soft tissue ratio, and patient body mass
      index. RESULTS: Tumor visualization was satisfactory for 88 patients (66%) and
      unsatisfactory for 45 patients (34%). Median time to treatment start was 6 days
      in the success group (range, 2-18 days) and 15 days (range, 3-63 days) in the
      failure group. A stage T2 (P=.04), larger tumor size (volume of 15.3 cm(3) vs 6.5
      cm(3) in success and failure group, respectively) (P<.0001), and higher tumor
      density (0.86 g/cm(3) vs 0.79 g/cm(3)) were predictive of adequate detection.
      There was a 63% decrease in failure risk with every 1-cm increase in maximum
      tumor dimension (relative risk for failure = 0.37, CI=0.23-0.60, P=.001). A
      diameter of 3.6 cm predicted a success probability of 80%. Histology, lung-to
      soft tissue ratio, distance to diaphragm, patient's body mass index, and tumor
      projection on vertebral column and mediastinum were not found to be predictive of
      success. CONCLUSIONS: Tumor size, volume, and density were the most predictive
      factors of a successful XSight Lung tumor tracking. Tumors >3.5 cm have >=80%
      chance of being adequately visualized and therefore should all be considered for
      direct tumor tracking.

PMID- 23953637
TI  - Long-term outcomes of fractionated stereotactic radiation therapy for pituitary
      adenomas at the BC Cancer Agency.
AB  - PURPOSE: To assess the long-term disease control and toxicity outcomes of
      fractionated stereotactic radiation therapy (FSRT) in patients with pituitary
      adenomas treated at the BC Cancer Agency. METHODS AND MATERIALS: To ensure a
      minimum of 5 years of clinical follow-up, this study identified a cohort of 76
      patients treated consecutively with FSRT between 1998 and 2007 for pituitary
      adenomas: 71% (54/76) had nonfunctioning and 29% (22/76) had functioning adenomas
      (15 adrenocorticotrophic hormone-secreting, 5 growth hormone-secreting, and 2
      prolactin-secreting). Surgery was used before FSRT in 96% (73/76) of patients. A
      median isocenter dose of 50.4 Gy was delivered in 28 fractions, with 100% of the
      planning target volume covered by the 90% isodose. Patients were followed up
      clinically by endocrinologists, ophthalmologists, and radiation oncologists.
      Serial magnetic resonance imaging was used to assess tumor response. RESULTS:
      With a median follow-up time of 6.8 years (range, 0.6 - 13.1 years), the 7-year
      progression-free survival was 97.1% and disease-specific survival was 100%. Of
      the 2 patients with tumor progression, both had disease control after salvage
      surgery. Of the 22 patients with functioning adenomas, 50% (11/22) had complete
      and 9% (2/22) had partial responses after FSRT. Of the patients with normal
      pituitary function at baseline, 48% (14/29) experienced 1 or more hormone
      deficiencies after FSRT. Although 79% (60/76) of optic chiasms were at least
      partially within the planning target volumes, no patient experienced radiation
      induced optic neuropathy. No patient experienced radionecrosis. No secondary
      malignancy occurred during follow-up. CONCLUSION: In this study of long-term
      follow-up of patients treated for pituitary adenomas, FSRT was safe and
      effective.

PMID- 23953638
TI  - Can differences in life cycle explain differences in invasiveness? - A study on
      Anguillicola novaezelandiae in the European eel.
AB  - Anguillicola crassus is the most invasive species of its genus and it is a
      successful colonizer of different eel species worldwide. It is so far the only
      species of the genus Anguillicola whose life cycle has been studied completely.
      To analyse whether differences in life cycle may explain differences in
      invasiveness, we infected European eels with Anguillicola novaezelandiae under
      laboratory conditions. Anguillicola novaezelandiae shows a synchronized
      development in the European eel. Eggs with second-stage larvae appeared 120 days
      after infection. No density-dependent effect in parasite development could be
      found for A. novaezelandiae. The present study shows that the life cycle of A.
      novaezelandiae differs on final host level compared with A. crassus in ways which
      result in a less successful invasion of new host species.

PMID- 23953639
TI  - Is it really a hamartoma? Bringing awareness to the possibility of an
      intravesical phallus in the aphallic 46,xy cloacal exstrophy patient.

PMID- 23953640
TI  - Restless legs syndrome and akathisia as manifestations of acute pontine
      infarction.
AB  - Although restless legs syndrome (RLS) and akathisia have similar clinical
      manifestations and seem to share a common pathophysiology, they are regarded as
      distinct clinical syndromes. We present three patients with acute pontine
      infarction and RLS or akathisia as clinical manifestations. They presented with
      abrupt onset of restlessness of various body parts, as well as other neurological
      signs including dysarthria or weakness of the legs. Brain MRI of all three
      patients showed acute pontine infarction. The clinical syndrome in two of the
      patients was compatible with RLS and one with akathisia. Their symptoms improved
      after a brief period. Our finding of secondary RLS and akathisia as
      manifestations of acute pontine infarction provides information that assists in
      understanding the common anatomical and pathophysiological basis of RLS and
      akathisia. 

PMID- 23953641
TI  - Increased densities of nitric oxide synthase expressing neurons in the temporal
      cortex and the hypothalamic paraventricular nucleus of polytoxicomanic heroin
      overdose victims: possible implications for heroin neurotoxicity.
AB  - Heroin is one of the most dangerous drugs of abuse, which may exert various
      neurotoxic actions on the brain (such as gray matter loss, neuronal apoptosis,
      mitochondrial dysfunction, synaptic defects, depression of adult neurogenensis,
      as well as development of spongiform leucoencephalopathy). Some of these toxic
      effects are probably mediated by the gas nitric oxide (NO). We studied by
      morphometric analysis the numerical density of neurons expressing neuronal nitric
      oxide synthase (nNOS) in cortical and hypothalamic areas of eight heroin overdose
      victims and nine matched controls. Heroin addicts showed significantly increased
      numerical densities of nNOS immunoreactive cells in the right temporal cortex and
      the left paraventricular nucleus. Remarkably, in heroin abusers, but not in
      controls, we observed not only immunostained interneurons, but also cortical
      pyramidal cells. Given that increased cellular expression of nNOS was accompanied
      by elevated NO generation in brains of heroin addicts, these elevated levels of
      NO might have contributed to some of the known toxic effects of heroin (for
      example, reduced adult neurogenesis, mitochondrial pathology or disturbances in
      synaptic functioning). 

PMID- 23953642
TI  - Prevalence of cerebrospinal fluid oligoclonal IgG bands in Greek patients with
      clinically isolated syndrome and multiple sclerosis.
AB  - Lower prevalence of cerebrospinal fluid oligoclonal IgG bands (IgG-OCBs) has been
      reported in multiple sclerosis (MS) patients from Southern Europe compared to
      other western countries. OBJECTIVES: We aimed to determine the prevalence of CSF
      OCBs in Greek MS patients and to examine their relation with some selected
      clinical and demographical features. METHODS: Included patients fulfilled the
      2005 McDonald criteria for definite MS (CDMS) or clinically isolated syndrome
      (CIS) and had a spinal tap performed between 2006 and 2010. Paired CSF and plasma
      samples were analyzed using isoelectric focusing followed by IgG-specific
      immunofixation. A pattern of two or more bands present only in the CSF was
      defined as positive. OCB status was correlated with age at disease onset, initial
      symptomatology, relapse rate, disease subtype, disease duration, medication, EDSS
      score and MSSS. RESULTS: Of the 231 included patients (53.2% with CDMS and 48.6%
      with CIS) 67.5% had OCBs. The prevalence of positive patterns did not differ
      between CIS and CDMS patients (67.6% vs. 67.5%, respectively). OCB-positive
      patients were younger than OCB-negative patients (35.2+/-10.3 vs. 38.7+/-11.8
      years respectively, p=0.022) and had more frequently cervical spinal cord lesions
      (x2=7.08, p=0.008). No difference was observed between the two subgroups in the
      other studied disease parameters. CONCLUSION: Despite the lower frequency of
      positive IgG-OCB patterns in our patients, both subgroups were mostly similar
      with regard to their clinical and demographic characteristics suggesting that the
      OCB status lacks prognostic significance in MS.

PMID- 23953643
TI  - Astrogenomics: big data, old problems, old solutions?

PMID- 23953644
TI  - Anti-NMDAR encephalitis misdiagnosed as Hashimoto's encephalopathy.
AB  - Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a well-defined
      autoimmune disorder. Hashimoto's encephalopathy (HE) is a still controversial
      entity, lacking definite diagnostic criteria. We described a 14-year-old-girl
      presenting with a clinical picture consistent with the diagnosis of anti-NMDAR
      encephalitis, confirmed by NMDAR antibody testing. Four years earlier, she had
      presented a similar episode of acute encephalopathy diagnosed as HE. Anti-NMDAR
      encephalitis and HE share similar clinical features so that the differential
      diagnosis can be difficult if specific antibodies are not tested. The correct
      diagnosis of anti-NMDAR encephalitis is crucial to plan the appropriate
      management and follow-up, namely in term of oncological screening, since it can
      be paraneoplastic in origin. We suggest to re-evaluate the clinical history of
      all subjects with previous HE diagnosis in order to evaluate the possible
      diagnosis of anti-NMDAR encephalitis and plan the appropriate management of these
      patients.

PMID- 23953645
TI  - Modulation of human postprandial lipemia by changing ratios of polyunsaturated to
      saturated (P/S) fatty acid content of blended dietary fats: a cross-over design
      with repeated measures.
AB  - BACKGROUND: Postprandial lipemia (PL) contributes to coronary artery disease. The
      fatty acid composition of dietary fats is potentially a modifiable factor in
      modulating PL response. METHODS: This human postprandial study evaluated 3 edible
      fat blends with differing polyunsaturated to saturated fatty acids (P/S) ratios
      (POL = 0.27, AHA = 1.00, PCAN = 1.32). A cross-over design included mildly
      hypercholestrolemic subjects (9 men and 6 women) preconditioned on test diets
      fats at 31% energy for 7 days prior to the postprandial challenge on the 8th day
      with 50 g test fat. Plasma lipids and lipoproteins were monitored at 0, 1.5, 3.5,
      5.5 and 7 hr. RESULTS: Plasma triacylglycerol (TAG) concentrations in response to
      POL, AHA or PCAN meals were not significant for time x test meal interactions (P
      > 0.05) despite an observed trend (POL > AHA > PCAN). TAG area-under-the-curve
      (AUC) increased by 22.58% after POL and 7.63% after PCAN compared to AHA
      treatments (P > 0.05). Plasma total cholesterol (TC) response was not significant
      between meals (P > 0.05). Varying P/S ratios of test meals significantly altered
      prandial high density lipoprotein-cholesterol (HDL-C) concentrations (P < 0.001)
      which increased with decreasing P/S ratio (POL > AHA > PCAN). Paired comparisons
      was significant between POL vs PCAN (P = 0.009) but not with AHA or between AHA
      vs PCAN (P > 0.05). A significantly higher HDL-C AUC for POL vs AHA (P = 0.015)
      and PCAN (P = 0.001) was observed. HDL-C AUC increased for POL by 25.38% and
      16.0% compared to PCAN and AHA respectively. Plasma low density lipoprotein
      cholesterol (LDL-C) concentrations was significant (P = 0.005) between meals and
      significantly lowest after POL meal compared to PCAN (P = 0.004) and AHA (P >
      0.05) but not between AHA vs PCAN (P > 0.05). AUC for LDL-C was not significant
      between diets (P > 0.05). Palmitic (C16:0), oleic (C18:1), linoleic (C18:2) and
      linolenic (C18:3) acids in TAGs and cholesteryl esters were significantly
      modulated by meal source (P < 0.05). CONCLUSIONS: P/S ratio of dietary fats
      significantly affected prandial HDL-C levels without affecting lipemia.

PMID- 23953646
TI  - Trait stacking via targeted genome editing.
AB  - Modern agriculture demands crops carrying multiple traits. The current paradigm
      of randomly integrating and sorting independently segregating transgenes creates
      severe downstream breeding challenges. A versatile, generally applicable solution
      is hereby provided: the combination of high-efficiency targeted genome editing
      driven by engineered zinc finger nucleases (ZFNs) with modular 'trait landing
      pads' (TLPs) that allow 'mix-and-match', on-demand transgene integration and
      trait stacking in crop plants. We illustrate the utility of nuclease-driven TLP
      technology by applying it to the stacking of herbicide resistance traits. We
      first integrated into the maize genome an herbicide resistance gene, pat, flanked
      with a TLP (ZFN target sites and sequences homologous to incoming DNA) using
      WHISKERSTM-mediated transformation of embryogenic suspension cultures. We
      established a method for targeted transgene integration based on microparticle
      bombardment of immature embryos and used it to deliver a second trait precisely
      into the TLP via cotransformation with a donor DNA containing a second herbicide
      resistance gene, aad1, flanked by sequences homologous to the integrated TLP
      along with a corresponding ZFN expression construct. Remarkably, up to 5% of the
      embryo-derived transgenic events integrated the aad1 transgene precisely at the
      TLP, that is, directly adjacent to the pat transgene. Importantly and consistent
      with the juxtaposition achieved via nuclease-driven TLP technology, both
      herbicide resistance traits cosegregated in subsequent generations, thereby
      demonstrating linkage of the two independently transformed transgenes. Because
      ZFN-mediated targeted transgene integration is becoming applicable across an
      increasing number of crop species, this work exemplifies a simple, facile and
      rapid approach to trait stacking. 

PMID- 23953647
TI  - Goldenhar syndrome and medulloblastoma: a coincidental association? The first
      case report.
AB  - BACKGROUND: Features of Goldenhar syndrome include several craniofacial anomalies
      of structures derived from the first and second pharyngeal arches, as well as
      vertebral, cardiac and renal systems abnormalities. In addition, Goldenhar
      patients were reported to manifest a variety of central nervous system anomalies
      and several types of neoplasias. CASE HISTORY AND DISCUSSION: The first case of
      medulloblastoma in a patient with Goldenhar syndrome is presented here. There is
      no clear association between these two pathologies. We speculate that aberrant
      events during the migration of neural crest cells in early stages of development
      could be the basis of an association between medulloblastoma and Goldenhar
      syndrome. The case history suggests other possible etiological contributing
      factors to the development of medulloblastoma, such as patient's history of
      trauma and/or early childhood exposure to ionizing radiation.

PMID- 23953648
TI  - Dielectric spectroscopy of concentrated colloidal suspensions.
AB  - A comparison between experimental measurements and theoretical calculations of
      the permittivity and conductivity of concentrated colloidal suspensions is
      presented. Dielectric spectroscopy measurements for 100nm and 200nm diameter
      polystyrene spheres at volume fractions between phi=0.01-0.18 and electrolyte
      concentrations 0.01-1mM KCl (P.J. Beltramo, E.M. Furst, Langmuir 28 (2012) 10703
      10712) are compared to cell-model calculations that account for the hydrodynamic
      and electrokinetic interactions between particles (F. Carrique, F.J. Arroyo, M.L.
      Jimenez, A.V. Delgado, J. Chem. Phys. 118 (2003) 1945-1956). Under most
      conditions, there is good agreement between experiment and theory. At low ionic
      strengths, the dielectric increment exhibits a low-frequency plateau in the
      experimental spectroscopy and cell model calculations. However, at the highest
      ionic strengths, the cell model predicts a low frequency plateau that is not
      observed experimentally. The conductivity increments qualitatively agree over all
      volume fractions, ionic strengths and frequencies. 

PMID- 23953649
TI  - Macroscopic and molecular approaches of enrofloxacin retention in soils in
      presence of Cu(II).
AB  - The co-adsorption of copper and the fluoroquinolone antibiotic enrofloxacin (ENR)
      at the water-soil interface was studied by means of batch adsorption experiments,
      and extended X-ray absorption fine structure (EXAFS) spectroscopy. The system was
      investigated over a pH range between 6 and 10, at different contact times, ionic
      strengths, and ENR concentrations. Adsorption coefficient - Kd - was determined
      at relevant environmental concentrations and the value obtained in water at a
      ionic strength imposed by the soil and at soil natural pH was equal to 0.66Lg(
      1). ENR adsorption onto the soil showed strong pH dependence illustrating the
      influence of the electrostatic interactions in the sorption processes. The
      simultaneous co-adsorption of ENR and Cu(II) on the soil was also investigated.
      The presence of Cu(II) strongly influenced the retention of the antibiotic,
      leading to an increase up to 35% of adsorbed ENR amount. The combined
      quantitative and spectroscopic results showed that Cu(II) and ENR directly
      interacted at the water-soil interface to form ternary surface complexes. Cu K
      edge EXAFS data indicated a molecular structure where the carboxylate and
      carbonyl groups of ENR coordinate to Cu(II) to form a 6-membered chelate ring and
      where Cu(II) bridges between ENR and the soil surface sites. Cu(II) bonds
      bidentately to the surface in an inner-sphere mode. Thus, the spectroscopic data
      allowed us to propose the formation of ternary surface complexes with the
      molecular architecture soil-Cu(II)-ENR. 

PMID- 23953650
TI  - Tailor-made polyfluoroacrylate and its block copolymer by RAFT polymerization in
      miniemulsion; improved hydrophobicity in the core-shell block copolymer.
AB  - Controlled/living radical polymerization (CRP) of a fluoroacrylate was
      successfully carried out in miniemulsion by Reversible Addition Fragmentation
      chain Transfer (RAFT) process. In this case, 2,2,3,3,4,4,4-heptafluorobutyl
      acrylate (HFBA) was polymerized using 2-cyanopropyl dodecyl trithiocarbonate
      (CPDTC) as RAFT agent, Triton X-405 and sodium dodecyl sulfonate (SDS) as
      surfactant, and potassium persulphate (KPS) or 2,2'-azobis isobutyronitrile
      (AIBN) as initiator. Being compatible with hydrophobic fluoroacrylate, this RAFT
      agent offered very high conversion and good control over the molecular weight of
      the polymer. The miniemulsion was stable without any costabilizer. The long chain
      dodecyl group (-C12H25) (Z-group in the RAFT agent) had beneficial effect in
      stabilizing the miniemulsion. When 2-cyano 2-propyl benzodithioate (CPBD) (Z=
      C6H5) was used as RAFT agent, the conversion was less and particle size
      distribution was very broad. Block copolymerization with butyl acrylate (BA)
      using PHFBA as macro-RAFT agent showed core-shell morphology with the aggregation
      of PHFBA segment in the shell. GPC as well as DSC analysis confirmed the
      formation of block copolymer. The core-shell morphology was confirmed by TEM
      analysis. The block copolymers (PHFBA-b-PBA) showed significantly higher water
      contact angle (WCA) showing much better hydrophobicity compared to PHFBA alone. 

PMID- 23953651
TI  - Adsorption of alkaloids on ordered mesoporous carbon.
AB  - An ordered mesoporous carbon (OMC) adsorbent was synthesized, characterized, and
      evaluated for effective separation and purification of alkaloid compounds from
      aqueous solutions. The OMC adsorbent has a large BET specific surface area
      (1532.2m(2)/g), large pore volume (2.13cm(3)/g), and narrow pore diameter
      distribution with a median pore diameter of 4.21nm. Berberine hydrochloride,
      colchicine, and matrine were selected as the model compounds for evaluating the
      adsorption properties of the OMC adsorbent for alkaloid purification. Batch
      adsorption experiments of pure components in water were carried out to measure
      both adsorption equilibria and kinetics, and column breakthrough and desorption
      experiments were performed to validate the separation and regeneration efficacy
      of the OMC adsorbent. The adsorption equilibrium capacities of berberine
      hydrochloride, colchicine, and matrine on the OMC adsorbent at 0.100mg/L and 298K
      are 450, 600, and 480mg/g, respectively, which are more than double the
      adsorption capacities of these compounds on two commonly used commercial resins
      (HPD300 and HPD100B) at similar conditions. Adsorption equilibrium of all three
      alkaloids could be obtained within 120min at 298K. The dynamic adsorption
      capacities determined from the breakthrough experiments are within 12% of the
      estimated equilibrium capacities from the Langmuir isotherms; and 74.3-92.8% of
      the adsorbed amounts could be recovered by desorbing with a 70% alcohol solution.
      The adsorption isotherms are analyzed with both Langmuir and Freundlich models,
      the adsorption kinetic data with the pseudo-first-order and pseudo-second-order
      models, and the breakthrough curves with four breakthrough models. The large
      adsorption capacity, fast adsorption rate, and easy regeneration make the ordered
      mesoporous carbon a promising adsorbent for adsorption and purification of
      alkaloid compounds from the extracts of herbal plants. 

PMID- 23953652
TI  - Visible light photocatalytic degradation of dyes by bismuth oxide-reduced
      graphene oxide composites prepared via microwave-assisted method.
AB  - Bi2O3-reduced graphene oxide (RGO) composites were successfully synthesized via
      microwave-assisted reduction of graphite oxide in Bi2O3 precursor solution using
      a microwave system. Their morphologies, structures, and photocatalytic
      performance in the degradation of methylene blue (MB) and methyl orange (MO) were
      characterized by scanning electron microscopy, transmission electron microscopy,
      X-ray diffraction spectroscopy, UV-vis absorption spectroscopy, and
      electrochemical impedance spectroscopy, respectively. The results show that the
      RGO addition can enhance the photocatalytic performance of Bi2O3-RGO composites.
      Bi2O3-RGO composite with 2 wt.% RGO achieves maximum MO and MB degradation rates
      of 93% and 96% at 240min under visible light irradiation, respectively, much
      higher than those for the pure Bi2O3 (78% and 76%). The enhanced photocatalytic
      performance is ascribed to the increased light adsorption and the reduction in
      electron-hole pair recombination in Bi2O3 with the introduction of RGO. 

PMID- 23953653
TI  - Formation and optical properties of silver perfluorodecanethiolate nanoparticles.
AB  - This article reports a new catalytic method for preparing nanoparticles of silver
      thiolate from silver nanoparticles scattered on a ZrO2-coated substrate. Such
      nanoparticles transform into silver (perfluoro) decanethiolate after immersion in
      a solution of (perfluoro) decanethiol in heptane. These transformations occur at
      room temperature and are catalysed by ZrO2. The silver decanethiolate is obtained
      as lamellar crystals while the silver perfluorodecanethiolate is obtained in
      amorphous state. The modifications of the sample optical properties due to this
      latter compound are studied in correlation with its surface morphology, according
      to different preparation conditions. It is shown that an antireflective effect in
      addition to the damping of the plasmon band of the silver nanoparticles can be
      responsible for a large transmittance enhancement in the near-UV and visible
      ranges. These effects are modulated by the possible oxidation of the silver
      nanoparticle surface. In the absence of silver oxidation, the silver
      perfluorodecanethiolate is obtained as contiguous spheroidal nanoparticles,
      while, in the presence of silver oxidation, this compound is mainly obtained as
      entangled nanowires. 

PMID- 23953654
TI  - An experience sampling study of worry and rumination in psychosis.
AB  - BACKGROUND: Increasing research effort is being dedicated to investigating the
      links between emotional processes and psychosis, despite the traditional
      demarcation between the two. Particular focus has alighted upon two specific
      anxious and depressive processes, worry and rumination, given the potential for
      links with aspects of delusions and auditory hallucinations. This study
      rigorously explored the nature of these links in the context of the daily life of
      people currently experiencing psychosis. METHOD: Experience sampling methodology
      (ESM) was used to assess the momentary links between worry and rumination on the
      one hand, and persecutory delusional ideation and auditory hallucinations on the
      other. Twenty-seven participants completed the 6-day experience sampling period,
      which required repeated self-reports on thought processes and experiences.
      Multilevel modelling was used to examine the links within the clustered data.
      RESULTS: We found that antecedent worry and rumination predicted delusional and
      hallucinatory experience, and the distress they elicited. Using interaction
      terms, we have shown that the links with momentary symptom severity were
      moderated by participants' trait beliefs about worry/rumination, such that they
      were reduced when negative beliefs about worry/rumination (meta-cognitions) were
      high. CONCLUSIONS: The current findings offer an ecologically valid insight into
      the influence of worry and rumination on the experience of psychotic symptoms,
      and highlight possible avenues for future intervention strategies.

PMID- 23953655
TI  - The group II metabotropic glutamate receptor agonist, LY379268, decreases
      methamphetamine self-administration in rats.
AB  - BACKGROUND: Given the problems associated with the escalation in methamphetamine
      (METH) use, the identification of more effective treatment strategies is
      essential. Group II metabotropic glutamate receptors (mGluRs) have been suggested
      to be a novel therapeutic target for psychostimulant addiction. We sought to test
      the ability of the selective group II mGluR agonist LY379268 to reduce METH self
      administration in rats. METHODS: Rats were trained to self-administer METH on a
      progressive ratio (PR) schedule. Animals were then switched to fixed ratio
      responding and given daily extended access (6 h/day) to METH self-administration
      for 14 days. Rats were then re-tested on the PR schedule. The effect of LY379268
      on METH-reinforced PR responding was determined before and after 14 days of
      extended access. To test for non-specific effects, a separate group of animals
      received LY379268 prior to a sucrose pellet-reinforced PR schedule. RESULTS:
      Animals escalated their daily intake of METH during extended access. PR
      responding did not change as a function of extended access. LY379268
      significantly attenuated METH reinforced responding, both before and after
      extended access. The degree of attenuation did not change as a function of
      extended access. LY379268 had no effect on sucrose pellet-reinforced responding
      at any dose. CONCLUSIONS: LY379268 selectively reduced the motivation to self
      administer METH. In contrast to data with other compounds, the sensitivity to the
      effects of LY379268 did not change following extended access to METH self
      administration. Group II mGluR agonists, therefore, may represent a relatively
      new class of compounds for the development of pharmacotherapies for METH
      addiction.

PMID- 23953656
TI  - HIV and people who use drugs in central Asia: confronting the perfect storm.

PMID- 23953657
TI  - Disparities in Latino substance use, service use, and treatment: implications for
      culturally and evidence-based interventions under health care reform.
AB  - BACKGROUND: The goal of this systematic literature review was to enhance
      understanding of substance use, service use, and treatment among Latino subgroups
      to improve access to care and treatment outcomes in an era of health care reform.
      METHODS: The authors used 13 electronic databases and manually searched the
      literature from January 1, 1978, to May 30, 2013. One hundred (69%) of 145
      primary research articles met the inclusion criteria. Two blinded, independent
      reviewers scored each article. Consensus discussions and a content expert
      reconciled discrepancies. RESULTS: Current rates of alcohol and substance abuse
      among Latinos are comparable to or surpass other U.S. ethnic groups. Disparities
      in access and quality of care are evident between Latinos and other ethnic
      groups. As a heterogeneous group, Latinos vary by geographic region in terms of
      substance of choice and their cultural identity takes precedence over general
      ethnic identity as a likely determinant of substance abuse behaviors. There is
      growing research interest in systems influencing treatment access and adherence
      among racial/ethnic and gender minority groups. However, studies on Latinos'
      service use and immediate treatment outcomes have been both limited in number and
      inconsistent in findings. CONCLUSIONS: This review identified human capital,
      quality of care, and access to culturally responsive care as key strategies to
      eliminate disparities in health and treatment quality. Implications are
      discussed, including the need for effectiveness studies on Latinos served by
      systems of care that, under health care reform, are seeking to maximize
      resources, improve outcomes, and reduce variation in quality of care.

PMID- 23953659
TI  - Blinding and controls in postoperative percutaneous pain management.

PMID- 23953658
TI  - Varenicline for smoking cessation among methadone-maintained smokers: a
      randomized clinical trial.
AB  - BACKGROUND: With smoking rates far exceeding the general population, methadone
      maintained (MMT) opiate-dependent smokers experience high rates of tobacco
      related health consequences. Previous treatment studies have used nicotine
      replacement and produced low quit rates. METHODS: We test, using a three-group
      randomized design, the efficacy of varenicline versus placebo, in comparison with
      nicotine replacement therapy (NRT) that combines nicotine patch prescription plus
      ad libitum nicotine rescue, for smoking cessation. We recruited methadone
      maintained smokers from nine treatment centers in southern New England and
      provided six months of treatment, and a minimal behavioral intervention at
      baseline (NCI's 5A's). Outcomes included carbon monoxide (CO) confirmed 7-day
      point smoking cessation prevalence at 6 months and self-reported change in mean
      cigarettes per day. RESULTS: The 315 participants had a mean age of 40, with 50%
      male and 79% non-Hispanic White, smoked an average of 19.6 (+/- 10.4)
      cigarettes/day, and had a mean daily methadone dose of 109 mg. Intent-to-treat
      analyses, with missing considered to be smoking, showed the rate of CO-confirmed
      7-day abstinence at 6-months was 5.4% overall, with varenicline 3.7% compared to
      placebo 2.2%, and NRT 8.3% (p>.05). Adherence rates during the 7-days immediately
      prior to 6-month assessment were 34.2% in varenicline, 34.4% in placebo, and
      48.8% in NRT. Between baseline and 6-months there was an overall self-reported
      mean reduction of 8.3 cigarettes/day. CONCLUSION: Varenicline did not increase
      quit rates over placebo. Smoking cessation rates in methadone-maintained smokers
      are low and novel treatment strategies are required.

PMID- 23953661
TI  - Limited hip rotation and non-contact anterior cruciate ligament injury: a case
      control study.
AB  - BACKGROUND: Insufficient hip flexibility, a limiting factor for lower extremity
      rotation, can cause great rotational stress and consequent injury to the knees
      and ankles. A limited range of motion (ROM) of the hip might be associated with
      increased risk of non-contact anterior cruciate ligament (ACL) injury. We
      investigated the association between the risk of non-contact ACL injured student
      athletes and limitations of hip ROM. METHODS: A case-control study was conducted
      at an orthopaedic clinic in Japan. Cases included all patients with non-contact
      ACL injury and without known marked alignment abnormalities who visited the
      orthopaedic clinic during 2000-2008. Controls included all patients with non-ACL
      sports-related injuries who visited the same clinic in 2000. The adjusted odds
      ratio of ROM of the hip was evaluated for non-contact ACL injury risk. RESULTS:
      These cases were 44 ACL cases and 123 controls aged 13-17 years. The odds ratios
      (ORs) of internal and external rotations of hip ROMs were adjusted for age, sex,
      BMI, type of sports and hip ROM (flexion, extension, adduction, abduction). The
      adjusted ORs for a 10 degrees  increase of the sum of the right and left internal
      hip rotations were 0.18 (95% confidence interval [CI], 0.10-0.34, p<0.0001), and
      0.23 (95% CI, 0.14-0.39, p<0.0001) for external rotations, and the observed ORs
      were small. CONCLUSIONS: Data obtained from this small sample indicate that
      limited hip rotation ROMs in young athletes have the possibility of association
      with increased risk of non-contact ACL injury. LEVEL OF EVIDENCE: III - case
      control study.

PMID- 23953660
TI  - High early revision rate with the FPV patello-femoral unicompartmental
      arthroplasty.
AB  - BACKGROUND: Unicompartmental patellofemoral arthroplasties are uncommon however
      numbers are increasing and there are a variety of new prostheses available. The
      Femoro-Patella Vialla (FPV, Wright Medical) device was the second most commonly
      used patellofemoral unicompartmental prosthesis in the 2012 British National
      Joint Register. There are however no published outcomes data for this device.
      METHOD: 52 consecutive cases were studied prospectively using Oxford Knee Score
      and American Knee Society Scores pre-operatively and at follow up to a minimum of
      two years. RESULTS: Overall Oxford Knee Scores improved from 30 points pre
      operatively (36.6%) to 19 points (60%) at one-year. American Knee Society Knee
      scores improved from 51 points pre-operatively to 81 points at one-year. Function
      scores improved from 42 points pre-operatively to 70 points at one-year. 13 (25%)
      patients had an excellent outcome with pain abolished and near normal knee
      function. 11 (21%) patients gained very little improvement and scored their knees
      similar or worse to their pre-operative state. There were no infective or
      thromboembolic complications. Seven cases have been revised to a total knee
      replacement for on-going pain in six cases and progression of arthritis in the
      tibio-femoral compartments in one case. The patellar button was found to be very
      poorly fixed in all cases that were revised. CONCLUSION: Early results with the
      FPV prosthesis demonstrate that successful outcomes can be achieved however the
      results were unpredictable and a significant minority of patients had on-going
      symptoms that they found unacceptable. The early revision rate was high in this
      series.

PMID- 23953662
TI  - Mismatch repair as a prognostic marker for adjuvant therapy in colorectal cancer 
      how soon is now?

PMID- 23953663
TI  - Circulating tumor cells versus tumor-derived cell-free DNA: rivals or partners in
      cancer care in the era of single-cell analysis?

PMID- 23953664
TI  - Duration perception in crossmodally-defined intervals.
AB  - How humans perform duration judgments with multisensory stimuli is an ongoing
      debate. Here, we investigated how sub-second duration judgments are achieved by
      asking participants to compare the duration of a continuous sound to the duration
      of an empty interval in which onset and offset were marked by signals of
      different modalities using all combinations of visual, auditory and tactile
      stimuli. The pattern of perceived durations across five stimulus durations
      (ranging from 100 ms to 900 ms) follows the Vierordt Law. Furthermore, intervals
      with a sound as onset (audio-visual, audio-tactile) are perceived longer than
      intervals with a sound as offset. No modality ordering effect is found for
      visualtactile intervals. To infer whether a single modality-independent or
      multiple modality-dependent time-keeping mechanisms exist we tested whether
      perceived duration follows a summative or a multiplicative distortion pattern by
      fitting a model to all modality combinations and durations. The results confirm
      that perceived duration depends on sensory latency (summative distortion).
      Instead, we did not find evidence for multiplicative distortions. The results of
      the model and the behavioural data support the concept of a single time-keeping
      mechanism that allows for judgments of durations marked by multisensory stimuli.

PMID- 23953665
TI  - Clinical and health costs impact of progress in diagnosis and treatment in venous
      thromboembolic disease: evolution in 15 years.
AB  - BACKGROUND: The therapeutic and diagnostic approach in deep vein thrombosis (DVT)
      has changed enormously in the last two decades with the introduction of
      ultrasound, low-molecular-weight heparin (LMWH), and premature motion. The aim of
      this study is to evaluate these changes and analyze their clinical and economic
      aspects. METHODS: We registered all inpatients with a diagnosis of DVT during
      1994 (n=110) and 2009 (n=75) and their sociodemographic and clinical features in
      a descriptive observational design. We performed a comparison of diagnostic
      techniques, length of stay, inpatient complications, and costs thus derived for
      both series, based on 2009 prices, so that we could get comparable results.
      RESULTS: Ninety-one percent of inpatients in 1994 were diagnosed by venography,
      whereas, in 2009, the diagnosis was based on clinical features, D-dimer, and
      ultrasound in 100% of patients. Inpatient treatment went from 7% LMWH in 1994 to
      96% in 2009, and as outpatient from 82% acenocumarol to 90.6% LMWH. Complications
      decreased by 13.3%. Length of stay was 2.7 higher in 1994. Globally, the cost per
      patient decreased by 63.39%, based primarily on reduced length of stay.
      CONCLUSIONS: The current diagnostic and therapeutic approach in DVT allows for
      effective treatment, fewer complications, and a drastic reduction in inpatient
      costs.

PMID- 23953666
TI  - Endovascular treatment of cystic adventitial disease of the popliteal artery.
AB  - Cystic adventitial disease of the popliteal artery is an uncommon cause of
      intermittent claudication in young patients. Several treatment options are
      available, oriented to either drainage of the cyst and/or arterial
      reconstruction. Endovascular techniques have been used in exceptional cases to
      treat this condition, mostly balloon angioplasty and only 2 cases of stenting,
      with mixed to poor results. We report the case of a 36-year-old female patient
      with claudication who was treated with primary stenting with long-term
      symptomatic relief and arterial patency. 

PMID- 23953667
TI  - Successful management of postoperative necrotizing pancreatitis after infrarenal
      abdominal aortic aneurysm repair.
AB  - We present a case of severe necrotizing pancreatitis that developed after
      elective repair of an abdominal aortic aneurysm. Surgeons are confronted in cases
      of postoperative acute pancreatitis with the dilemma of potential intraabdominal
      infection and the high risk of a subsequent infection of the retroperitoneal
      synthetic material. The therapeutic options range from a restrictive regime to
      radical necrosectomy and multivisceral resection. 

PMID- 23953668
TI  - The role of gene conversion in preserving rearrangement hotspots in the human
      genome.
AB  - Hotspots of non-allelic homologous recombination (NAHR) have a crucial role in
      creating genetic diversity and are also associated with dozens of genomic
      disorders. Recent studies suggest that many human NAHR hotspots have been
      preserved throughout the evolution of primates. NAHR hotspots are likely to
      remain active as long as the segmental duplications (SDs) promoting NAHR retain
      sufficient similarity. Here, we propose an evolutionary model of SDs that
      incorporates the effect of gene conversion and compare it with a null model that
      assumes SDs evolve independently without gene conversion. The gene conversion
      model predicts a much longer lifespan of NAHR hotspots compared with the null
      model. We show that the literature on copy number variants (CNVs) and genomic
      disorders, and also the results of additional analysis of CNVs, are all more
      consistent with the gene conversion model. 

PMID- 23953669
TI  - Allostatic load amplifies the effect of blood lead levels on elevated blood
      pressure among middle-aged U.S. adults: a cross-sectional study.
AB  - BACKGROUND: Scientists and regulators have sought to understand whether and how
      physiologic dysregulation due to chronic stress exposure may enhance
      vulnerability to the adverse health effects of toxicant exposures. We conducted a
      cross-sectional study to determine whether allostatic load (AL), a composite
      measure of physiologic response to chronic exposure to stress, amplifies the
      effect of lead exposure on blood pressure among middle-aged adults. METHODS: We
      analyzed associations between blood lead levels and blood pressure in a
      nationally representative sample of 8,194 U.S. adults (aged 40-65 years)
      participating in the National Health and Nutritional Examination Survey, 1999-
      2008. Outcomes were elevated systolic (>= 140 mm Hg) and diastolic (>= 90 mm Hg)
      blood pressure. AL was defined as the aggregate score of seven components,
      reflecting dysregulation of the cardiovascular, inflammatory, and endocrine
      systems. RESULTS: Logistic regression models showed a linear dose-response
      relationship for quintiles of blood lead and elevated systolic blood pressure in
      the high AL group (p = 0.03) but not the low AL group (p = 0.24). Similarly, the
      relationship between lead exposure and elevated diastolic blood pressure was
      stronger among the high AL group than the low AL group. Within the high AL group,
      the fourth and fifth quintiles had significantly elevated odds of elevated blood
      pressure compared to lowest quintile [OR = 1.92, (95% CI, 1.07, 3.47) and OR
      =2.28 (95% CI, 1.33, 3.91), respectively]. In the low AL group, none of the
      quintile effects were significantly different than the referent group although
      there was evidence of a linear trend (p =0.03). The lead by AL interaction term
      was not statistically significant for either systolic or diastolic blood pressure
      models. CONCLUSIONS: Results suggest that higher AL may amplify the adverse
      effects of lead on blood pressure. Future research should assess the implications
      of cumulative exposures to environmental and social stressors for regulatory
      decision-making.

PMID- 23953670
TI  - Validation of shear wave elastography in skeletal muscle.
AB  - Skeletal muscle is a very dynamic tissue, thus accurate quantification of
      skeletal muscle stiffness throughout its functional range is crucial to improve
      the physical functioning and independence following pathology. Shear wave
      elastography (SWE) is an ultrasound-based technique that characterizes tissue
      mechanical properties based on the propagation of remotely induced shear waves.
      The objective of this study is to validate SWE throughout the functional range of
      motion of skeletal muscle for three ultrasound transducer orientations. We
      hypothesized that combining traditional materials testing (MTS) techniques with
      SWE measurements will show increased stiffness measures with increasing tensile
      load, and will correlate well with each other for trials in which the transducer
      is parallel to underlying muscle fibers. To evaluate this hypothesis, we
      monitored the deformation throughout tensile loading of four porcine brachialis
      whole-muscle tissue specimens, while simultaneously making SWE measurements of
      the same specimen. We used regression to examine the correlation between Young's
      modulus from MTS and shear modulus from SWE for each of the transducer
      orientations. We applied a generalized linear model to account for repeated
      testing. Model parameters were estimated via generalized estimating equations.
      The regression coefficient was 0.1944, with a 95% confidence interval of (0.1463
      0.2425) for parallel transducer trials. Shear waves did not propagate well for
      both the 45 degrees  and perpendicular transducer orientations. Both parallel SWE
      and MTS showed increased stiffness with increasing tensile load. This study
      provides the necessary first step for additional studies that can evaluate the
      distribution of stiffness throughout muscle. 

PMID- 23953671
TI  - Amputee locomotion: spring-like leg behavior and stiffness regulation using
      running-specific prostheses.
AB  - Carbon fiber running-specific prostheses (RSPs) have allowed individuals with
      lower extremity amputation (ILEA) to participate in running. It has been
      established that as running speed increases, leg stiffness (Kleg) remains
      constant while vertical stiffness (Kvert) increases in able-bodied runners. The
      Kvert further depends on a combination of the torsional stiffnesses of the joints
      (joint stiffness; Kjoint) and the touchdown joint angles. Thus, an increased
      understanding of spring-like leg function and stiffness regulation in ILEA
      runners using RSPs is expected to aid in prosthetic design and rehabilitation
      strategies. The aim of this study was to investigate stiffness regulation to
      various overground running speeds in ILEA wearing RSPs. Eight ILEA performed
      overground running at a range of running speeds. Kleg, Kvert and Kjoint were
      calculated from kinetic and kinematic data in both the intact and prosthetic
      limbs. Kleg and Kvert in both the limbs remained constant when running speed
      increased, while intact limbs in ILEA running with RSPs have a higher Kleg and
      Kvert than residual limbs. There were no significant differences in Kankle, Kknee
      and touchdown knee angle between the legs at all running speeds. Hip joints in
      both the legs did not demonstrate spring-like function; however, distinct impact
      peaks were observed only in the intact leg hip extension moment at the early
      stance phase, indicating that differences in Kvert between limbs in ILEA are due
      to attenuating shock with the hip joint. Therefore, these results suggest that
      ILEA using RSPs has a different stiffness regulation between the intact and
      prosthetic limbs during running. 

PMID- 23953672
TI  - Dynamic regulation of innate immunity by ubiquitin and ubiquitin-like proteins.
AB  - Protein post-translational modifications (PTMs) are central to the host innate
      immune regulations. Dynamically, PTMs fine-tune the spatial and temporary
      responses of immune- and non-immune-cells, in accordance with extracellular and
      intracellular stresses. Ubiquitin and ubiquitin-like proteins (Ubls) are emerging
      as the important multi-functional signals, controlling the activation, stability,
      affinity and location of many signaling proteins. Recent investigations, at the
      molecular-cellular-animal models, have shed new light on the versatility of the
      ubiquitin, SUMO and ISG15, for shaping the strength and duration of the innate
      immune responses. This review summarizes our current knowledge on the functions
      and regulatory mechanisms of the ubiquitin and Ubls in the innate immunity, the
      first line of host defense against microbial infection. 

PMID- 23953673
TI  - Identification and characterization of new mechanisms in vascular oestrogen
      signalling.
AB  - Oestrogen exerts vasculoprotective effects in different experimental settings
      through inhibition of vascular smooth muscle cell proliferation, stimulation of
      nitric oxide production and attenuation of inflammation. Although these oestrogen
      evoked beneficial effects have been attributed to oestrogen receptor alpha
      (ERalpha), also ER beta (ERbeta) and the novel ER G protein-coupled receptor 30
      (GPR30)/G protein-coupled ER1 probably play significant roles in vascular
      oestrogen signalling. Oestrogen-evoked vasculoprotective effects are well
      documented in various experimental models, but the underlying mechanisms are
      still incompletely understood. The age hypothesis represents an interesting and
      promising model to explain the discrepancy between experimental data showing
      beneficial vascular effects of oestrogen treatment and the clinical findings on
      hormone replacement therapy obtained in big epidemiology surveys, where no
      protective effect from supplementation with oestrogen is observed. Identification
      of novel ERs expressed also in the vascular system offers exciting opportunities
      for the future to find and characterize the mechanisms behind oestrogen-evoked
      beneficial effects in vascular health and disease. Importantly, some vascular
      effects of pharmacological concentrations of oestrogen are ER-independent,
      suggesting that oestrogen besides its specific effects through ERalpha, ERbeta
      and GPR30 also affects vascular function via ER-independent mechanisms probably
      reflecting interaction of the hydrophobic oestrogen molecule with cell membrane
      properties. In this MiniReview, we focus on the importance of these different
      vascular ER subtypes in health and disease. 

PMID- 23953674
TI  - Ultrapulse carbon dioxide laser versus traditional deepithelialization in
      reduction mammoplasty and mastopexy: clinical outcomes and cost analysis.

PMID- 23953675
TI  - Use of the deltoid branch-based clavicular head of pectoralis major muscle flap
      in isolated sternoclavicular infections.
AB  - BACKGROUND: The pectoralis major (PM) flap is the workhorse flap for acute, sub
      acute and chronic sternoclavicular infections (SCIs). Attempts at using only the
      clavicular head of the pectoralis major muscle (CPM), based on internal mammary
      perforators or the thoracoacromial artery, have been reported. We describe the
      harvest of a deltoid branch-based flap (CPM-DTA) and examine its use in managing
      a series of isolated, acute and sub-acute sternoclavicular infections. METHODS:
      From 2007 to 2012, 28 subjects with SCI underwent PM flaps at our institution.
      Six were excluded for extensive chest wall involvement, and four were excluded
      from chronic osteomyelitis (5 months of infection or greater). Of the remaining
      18 patients with isolated SCI, 12 underwent traditional PM flaps (Group-A), while
      six underwent CPM-DTA (Group-B). Features studied include age, gender, co
      morbidities, culture, need for intra-operative extension of the sternoclavicular
      incision, postoperative complications, wound healing, time from infection onset
      to debridement, length of hospital stay, postoperative chest wall contour
      deformity and follow-up. RESULTS: Infections resolved and wounds healed in all
      patients following a single reconstructive procedure. Intra-operative need for
      extended incisions and postoperative ipsilateral anterior chest wall contour
      deformity are noted in all Group-A subjects but in no Group-B subjects.
      CONCLUSION: In patients with isolated, acute and sub-acute SCI, the CPM-DTA flap
      achieves effective wound closure while avoiding large sternal incisions and the
      morbidity associated with standard PM muscle harvest. Harvesting the CPM-DTA flap
      preserves the sternocostal head of the pectoralis major muscle and its
      thoracoacromial pedicle. This preserves the muscle for future flap use if
      necessary.

PMID- 23953676
TI  - [Reconstruction of transfixing loss of substance from the wing of the nose by
      composite graft of the controlateral nostril: about three cases].
AB  - INTRODUCTION: Reconstruction of the loss of transfixing substance from the nose
      wing is one of the most difficult procedures in facial plastic surgery. We
      propose a new technique consisting of a composite graft of the controlateral
      nostril among patients having an asymmetry of the nostrils. PATIENTS AND METHODS:
      A clinical study was carried out on three patients who had undergone a composite
      nasal graft. The graft was harvested from the nostril controlateral to the nasal
      defect then placed at the level of the previously prepared affected nostril.
      RESULTS: Three patients aged 27, 37 and 39years respectively received a
      controlateral nasal composite graft for the treatment of transfixing substance
      loss of the nose wing of less than 1cm. In all three cases, the result was judged
      to be very satisfactory by the surgeon and by all the patients. CONCLUSION: The
      controlateral nasal composite graft is a straightforward, quick and reliable
      technique to treat small losses of transfixing substance from the nose wing.
      However, because of an uncertain cicatricial ransom of the donor site, this
      technique must be compared to the auricular composite graft that is the technique
      of reference.

PMID- 23953677
TI  - Isolated mammillary body involvement on MRI in Wernicke's encephalopathy.
AB  - A 48-year-old woman, with a remote history of gastric-banding as well as recent
      onset post-prandial vomiting and excessive wine-drinking, was admitted with
      progressively-worsening gait incoordination. She showed gaze-evoked nystagmus and
      gait ataxia. Brain MRI revealed conspicuous, isolated, symmetrical T2/FLAIR
      hyperintensities and gadolinium-enhancement of the mammillary bodies. Serum
      thiamine and folate were low. Following thiamine and folate replacement therapy,
      her ataxia resolved. Given the rising number of bariatric procedures, we discuss
      the importance of recognizing thiamine-deficiency in these patients.
      Additionally, while isolated involvement of the mammillary bodies is a rare
      finding in this disorder, we highlight radiologic changes that neurologists
      should recognize. 

PMID- 23953678
TI  - Stroke-prone renovascular hypertensive rat as an animal model for stroke studies:
      from artery to brain.
AB  - High blood pressure is a main risk factor for both initial and recurrent stroke.
      Compared to the post stroke situation in normotension, the brain lesion is larger
      in hypertension, and the treatments may not be as effective. Thus, the results
      from healthy individuals may not be directly applied to the hypertensive. In
      fact, the high prevalence of hypertension in stroke patients and its devastating
      effect urge the necessity to integrate arterial hypertension in the study of
      stroke in order to better mimic the clinical situations. The first step to do so
      is to have an appropriate hypertensive animal model for stroke studies. Stroke
      prone renovascular hypertensive rat (RHRSP) introduced in 1998, is an animal
      model with acquired hypertension independent of genetic deficiency. The blood
      pressure begins to increase during the first week after constriction of bilateral
      renal arteries, and becomes sustained since around the 3rd month. Because the
      morphological and physiological changes of cerebral arteries are similar to those
      in hypertensive patients, the rats represent a higher than 60% incidence of
      spontaneous stroke. The animal model has several advantages: one hundred percent
      development of hypertension without gene modification, high similarity to human
      hypertension in cerebrovascular pathology and physiology, and easy establishment
      with low cost. Thus, the model has been extensively used in the investigation of
      ischemic stroke, and has been shown as a reliable animal model. This paper
      reviewed the features of RHRSP and its applications in the treatment and
      prevention of stroke, as well as the investigations of secondary lesions
      postischemic stroke.

PMID- 23953679
TI  - Minimization of bovine tuberculosis control costs in US dairy herds.
AB  - The objective of this study was to minimize the cost of controlling an isolated
      bovine tuberculosis (bTB) outbreak in a US dairy herd, using a stochastic
      simulation model of bTB with economic and biological layers. A model optimizer
      produced a control program that required 2-month testing intervals (TI) with 2
      negative whole-herd tests to leave quarantine. This control program minimized
      both farm and government costs. In all cases, test-and-removal costs were lower
      than depopulation costs, although the variability in costs increased for farms
      with high holding costs or small herd sizes. Increasing herd size significantly
      increased costs for both the farm and the government, while increasing indemnity
      payments significantly decreased farm costs and increasing testing costs
      significantly increased government costs. Based on the results of this model, we
      recommend 2-month testing intervals for herds after an outbreak of bovine
      tuberculosis, with 2 negative whole herd tests being sufficient to lift
      quarantine. A prolonged test and cull program may cause a state to lose its bTB
      free status during the testing period. When the cost of losing the bTB-free
      status is greater than $1.4 million then depopulation of farms could be preferred
      over a test and cull program. 

PMID- 23953682
TI  - Campylobacter infection associated with consumption of duck liver pate: a
      retrospective cohort study in the setting of near universal exposure.
AB  - SUMMARY: A retrospective cohort study was performed following several reported
      cases of gastrointestinal illness after a catered event. The attack rate was
      45/77 (58.4%) by clinical case definition, with four individuals confirmed to
      have Campylobacter. There was near universal exposure to most foodstuffs served;
      consumption of duck liver pate [relative risk (RR) 2.53, 95% confidence interval
      (CI) 1.05-6.10], mixed leaf salad (RR 2.91, 95% CI 1.22-6.92) and table water (RR
      undefined, P < 0.01) were associated with illness in univariate analysis, with
      only the latter associated in the final multivariable model (P < 0.001). Samples
      of cooked duck liver pate subsequently prepared using identical methods at the
      venue were contaminated with Campylobacter jejuni and C. coli; water sampling was
      negative. Making inferences about causation in the presence of near universal
      exposures in this study required consideration of the limitations of statistical
      analysis, with the most compelling evidence of the causal role of inadequately
      prepared duck liver pate provided by environmental investigation.

PMID- 23953683
TI  - Breast metastases from oligodendroglioma: an unusual extraneural spread in two
      young women and a review of the literature.
AB  - BACKGROUND: Extraneural dissemination of oligodendroglioma is rare. Cases of
      breast metastases have never been described in the literature. CASE REPORTS: We
      report the first two cases of young women with initial diagnosis of anaplastic
      oligodendroglioma who experienced mammary gland metastases and a review of the
      literature. RESULTS: Immunohistochemical analysis performed on material from both
      primary and metastatic sites did not allow to draw any conclusion on possible
      etiopathogenetic hypothesis. A review of literature yielded 35 cases of
      extracranial metastatic oligodendroglioma from 1989 to 2012. CONCLUSION: Though
      rare, extracranial dissemination from oligodendroglioma may occur not only in
      long surviving heavily pre-treated patients. The review of literature and these
      two cases suggest that spread is primarily to bone and then from bone to other
      organs through hematogenous route mostly due to leptomeningeal or dura mater
      invasion. Chemotherapy regimens similar to those commonly used for non metastatic
      oligodendroglioma are recommended for patients with good performance status.

PMID- 23953684
TI  - Chemotherapy-induced ovarian toxicity in patients affected by endocrine
      responsive early breast cancer.
AB  - Cytotoxic chemotherapy may variably affect ovarian function depending on age and
      ovarian reserve at diagnosis, type of chemotherapy and use of tamoxifen.
      Ascertaining whether a premenopausal patient with endocrine-responsive early
      breast cancer and chemotherapy-induced amenorrhea has reached menopause is
      essential not only in order to provide accurate information on residual
      fertility, but also to appropriately prescribe endocrine therapy. Indeed,
      aromatase inhibitors are contraindicated in women with residual ovarian reserve.
      However, the diagnosis of menopause in patients with chemotherapy-induced
      amenorrhea is challenging, since clinical features, follicle-stimulating hormone
      and estradiol levels may be inaccurate to this aim. Recent studies demonstrated
      that the anti-mullerian hormone may improve the assessment of ovarian reserve
      residual to chemotherapy in women with early breast cancer. Herein, we review the
      incidence of amenorrhea and menopause induced by cytotoxic chemotherapy in women
      affected by early breast cancer and the suggested mechanisms that sustain these
      side-effects. Furthermore, it has been scrutinized the potential of new markers
      of ovarian reserve that may facilitate the selection of appropriate endocrine
      treatment for premenopausal women who develop amenorrhea following adjuvant
      chemotherapy for early breast cancer.

PMID- 23953685
TI  - Clinical management of older persons with haemophilia.
AB  - Life expectancy for people with haemophilia (PWH) has improved and is now
      approaching that of the general population. The growing population of elderly PWH
      will therefore increasingly face the age-related morbidities such as
      cardiovascular diseases, malignant disease, liver disease, and bone and joint
      related diseases, as well as the lifestyle and psychosocial factors that
      accompany many of these conditions. For many PWH, frequent contact with
      haemophilia specialists within the comprehensive care centres supplants the
      relationship that individuals in the general population have with their general
      practitioners. As a result, there is a risk that elderly PWH may miss the chronic
      disease screening opportunities offered to the general population. This review
      focuses on the screening tests and examinations recommended for age-related
      comorbidities in the general population that may be applicable to the growing
      population of older people with haemophilia. 

PMID- 23953686
TI  - Design and synthesis of (4E)-4-(4-substitutedbenzylideneamino)-3-substituted-2,3
      dihydro-2-thioxothiazole-5-carbonitrile as novel A2A receptor antagonists.
AB  - Novel 2-thioxothiazole derivatives (6-19) as potential adenosine A2A receptor
      (A2AR) antagonists were synthesized. The strong interaction of the compounds (6
      19) with A2AR in docking study was confirmed by high binding affinity with human
      A2AR expressed in HEK293T cells using radioligand-binding assay. The compound 19
      demonstrated very high selectivity for A2AR as compared to standard A2AR
      antagonist SCH58261. Decrease in A2AR-coupled release of endogenous cAMP in
      treated HEK293T cells demonstrated in vitro A2AR antagonist potential of the
      compound 19. Attenuation in haloperidol-induced impairment (catalepsy) in Swiss
      albino male mice pre-treated with compound 19 is evocative to explore its
      prospective in therapy of PD. 

PMID- 23953687
TI  - High analgesic and anti-inflammatory in vivo activities of six new hybrids NSAIAs
      tetrahydropyran derivatives.
AB  - We present in this article syntheses of six new hybrids compounds (4-9) that were
      efficiently prepared in one or two steps (70-84.6%) from our previous prototype
      (+/-)-cis-4-chloro-6-(naphthalen-1-yl)-tetrahydro-2H-pyran-2-yl)methanol (3) and
      the NSAIAs: acetyl salicylic acid, indomethacin, ibuprofen, ketoprofen, naproxen
      and diclofenac. The acetic acid-induced writhing method is able to determine that
      all investigated new hybrids showed stronger antinociceptive properties (2- to 10
      fold less ED50 values) than their precursors. The highest antinociceptive effect
      was observed for compound 9 showing more than 10-fold less ED50 values than
      diclofenac and ninefold less ED50 value than compound 2. All compounds presented
      greater activity than the control group in the tail-flick test confirming the
      central antinociceptive effect. New hybrids did not alter the motor performance
      of mice by rota-rod performance and open-field tests. Investigated compounds 4-9
      were not toxic after oral administration (LD50 >2000mg/kg). 

PMID- 23953688
TI  - Cationic perylenediimide as a specific fluorescent binder to mismatch containing
      DNA.
AB  - Small ligand molecules, which can recognize thermodynamically unstable site
      within DNA, such as mismatch base pair, abasic site, and single-bulge, have
      attracted much attention because of their potential diagnostics and biological
      applications. In this paper, we describe the binding of cationic perylenediimide
      (cPDI) molecules to thymine-containing mismatch base pair in DNA and the
      formation of cPDI dimer at the mismatch site. The cPDI dimer exhibits a
      characteristic excimer emission at 650nm. For T/T mismatch containing DNA, the
      switching behavior from the PDI dimer (650nm) to the monomer (550nm) emission in
      specific response to Hg(2+) ion was observed. 

PMID- 23953689
TI  - Design, synthesis, biological and structural evaluation of functionalized
      resveratrol analogues as inhibitors of quinone reductase 2.
AB  - Resveratrol (3,5,4'-trihydroxylstilbene) has been proposed to elicit a variety of
      positive health effects including protection against cancer and cardiovascular
      disease. The highest affinity target of resveratrol identified so far is the
      oxidoreductase enzyme quinone reductase 2 (QR2), which is believed to function in
      metabolic reduction and detoxification processes; however, evidence exists
      linking QR2 to the metabolic activation of quinones, which can lead to cell
      toxicity. Therefore, inhibition of QR2 by resveratrol may protect cells against
      reactive intermediates and eventually cancer. With the aim of identifying novel
      inhibitors of QR2, we designed, synthesized, and tested two generations of
      resveratrol analogue libraries for inhibition of QR2. In addition, X-ray crystal
      structures of six of the resveratrol analogues in the active site of QR2 were
      determined. Several novel inhibitors of QR2 were successfully identified as well
      as a compound that inhibits QR2 with a novel binding orientation. 

PMID- 23953690
TI  - Inhibitory effects of p-dodecylaminophenol on the invasiveness of human
      fibrosarcoma cell line HT1080.
AB  - Cancer is a major cause of death, and the development of new anticancer drugs is
      urgently needed. Invasion and metastasis are the primary causes of death due to
      cancer rather than growth of the primary tumor. In the current study, we examined
      the anti-invasive effects of p-dodecylaminophenol (1), which was developed based
      on N-(4-hydroxyphenyl)retinamide (2), a synthetic amide of all-trans-retinoic
      acid (3). In HT1080 cells 1 inhibited growth, induced apoptosis and arrested the
      cell cycle in S phase in a dose-dependent manner. In addition, 1 significantly
      suppressed cell invasion, and the activity and mRNA expression of matrix
      metalloproteinase-9 (MMP-9). Furthermore, the expression of the reversion
      inducing cysteine-rich protein with Kazal motifs (RECK), which is a negative
      regulator of MMP-9, was increased by treatment with 1. These results suggest that
      1 could be an effective anti-cancer agent that suppresses cell growth through
      apoptosis induction and cell cycle arrest, which also inhibits cell invasion by
      decreasing MMP-9 expression due to an increase in RECK. Compound 1 might be
      useful clinically as a new and potent anticancer agent that could overcome
      adverse side effects of the retinoids. 

PMID- 23953691
TI  - Effects of the environment on dog semen parameters and testosterone
      concentration.
AB  - Whether a mammal reproduces seasonally or continuously depends mostly on the
      environment and its effects on the endocrine pattern. Although the dog was the
      first species to have been domesticated, little information is available on the
      changes in reproduction that have occurred since. In this study, we evaluated
      whether environmental stimuli can act as modulators of male gonadal activity in
      the dog at the latitude of Bari (Italy). Therefore, for 1 year, serum and seminal
      testosterone (T) concentrations, together with seminal parameters, were recorded
      monthly and evaluated in relation to environmental variables such as temperature,
      humidity, and photoperiod. We found that, in temperate regions, the annual serum
      T profile is not affected by environmental conditions, whereas seminal T profile
      peaks in October and reaches its nadir in April. The percentage of progressive
      motile spermatozoa is also dependent on environmental cues. The results support
      the intuitive idea that recorded data require a proper analysis to be meaningful.
      In fact, we found that, in the dog, environmental changes appear to affect male
      gonadal physiology, and this is clear when recorded data are analyzed monthly; in
      contrast, pooling data into seasonal groups hides monthly environmental
      variations. 

PMID- 23953692
TI  - Biochanin A affects steroidogenesis and estrogen receptor-beta expression in
      porcine granulosa cells.
AB  - Biochanin A, similar to other isoflavones, is present in soy and soy-based food,
      but predominantly in red clover. Red clover extract and biochanin A were reported
      to affect reproductive processes as well as to demonstrate menopause relief and
      anticancerogenic properties. Because porcine granulosa cells provide a suitable
      in vitro model for studying the intracellular mechanism of phytoestrogen action
      in the ovary, the objective of the study was to evaluate the in vitro effects of
      biochanin A on the following: (1) progesterone (P4) and estradiol (E2) secretion
      by granulosa cells, (2) viability of the granulosa cells, and (3) mRNA and
      protein expression of estrogen receptors alpha (ERalpha) and beta (ERbeta) in the
      granulosa cells harvested from both medium (3-6 mm) and large (>=8 mm) porcine
      ovarian follicles. RIA, alamarBlue assay, reverse transcriptase-polymerase chain
      reaction, and immunocytochemistry were used in the study to address the
      objectives. Biochanin A significantly inhibited P4 and did not affect E2
      secretion by porcine granulosa cells regardless of the size of follicles that
      served as the source of the cells. Cell viability was not affected by the
      treatment. Biochanin A did not alter ERalpha and ERbeta mRNA levels in the
      cultured porcine granulosa cells. In contrast, this isoflavone increased (P <
      0.05) the immunoexpression of ERbeta in the cells from both follicle types. In
      summary, biochanin A, similar to genistein and daidzein, affects follicular
      steroidogenesis and ER expression. Its effect on ERbeta protein was more intense
      compared with other previously examined phytoestrogens.

PMID- 23953693
TI  - Effects of in vitro growth culture duration and prematuration culture on
      maturational and developmental competences of bovine oocytes derived from early
      antral follicles.
AB  - Bovine ovaries offer a large pool of oocytes that could be used for in vitro
      production of embryos of genetically valuable animals. The effects of in vitro
      growth (IVG) culture duration (10, 12, and 14 days) on the viability and growth
      of bovine oocytes derived from early antral follicles (0.5-1 mm diameter) in this
      study. In addition, the effect of pre-IVM culture with phosphodiesterase
      inhibitor (3-isobutyl-1-methylxanthine) on nuclear maturation of IVG oocytes was
      also evaluated. In experiment 1, oocyte viability observed after 10 or 12 days of
      IVG culture was greater (P < 0.05) than that observed after 14 days of culture.
      Oocyte diameters and proportions of oocytes at metaphase II stage were greater (P
      < 0.05) when 12 or 14 days of IVG culture where used when compared with 10 days
      culture. In addition, the proportion of oocytes at metaphase II stage was greater
      (P < 0.05) when pre-IVM culture was performed for oocytes derived from 12 and 14
      days of IVG culture. When 12 and 14 days of IVG culture followed by pre-IVM
      culture were compared in experiment 2, cumulus cell membrane integrity was
      greater (P < 0.05) after 12 days. Blastocyst production rate for oocytes obtained
      after 12 days of IVG culture (24.5%) was greater (P < 0.05) than for oocytes
      obtained after 14 days (9.9%). In conclusion, 12 days IVG followed by pre-IVM
      culture was considered the optimal processing system for bovine oocytes derived
      from early antral follicles when oocyte viability, diameter, maturation, and
      development competences were considered.

PMID- 23953694
TI  - Stimulation for the compact parts of pedunculopontine nucleus: an available
      therapeutic approach in intractable epilepsy.

PMID- 23953695
TI  - One-year outcomes of percutaneous coronary intervention with the 38-mm Resolute
      zotarolimus-eluting stent.
AB  - This study was designed to prospectively evaluate the safety and efficacy of the
      38-mm Resolute zotarolimus-eluting stent (R-ZES). Drug-eluting stents with long
      lengths are needed to ensure coverage of long lesions in some patients. Patients
      recruited from the RESOLUTE US and RESOLUTE Asia studies were implanted with at
      least one 38-mm R-ZES. Up to 2 lesions (in separate vessels) could be implanted
      with length <=35 mm and a reference vessel diameter of 3.0 to 4.2 mm. The primary
      end point was 1-year target lesion failure, defined as cardiac death, target
      vessel myocardial infarction, or clinically driven target lesion
      revascularization. The 1-year target lesion failure rate using 1 vessel per
      patient was compared with a performance goal (19%) derived from historical data.
      There were 223 patients enrolled (n = 269 lesions). The mean age was 60.9 +/-
      10.9 years, 79% were men, and 38% had diabetes. Target lesion failure rate using
      a single-vessel analysis was 4.5%, and the upper limit of the 1-sided 95%
      confidence interval (7.5%) was less than the performance goal of 19%. A secondary
      analysis using all lesions resulted in a target lesion failure rate of 5.4%
      (upper limit of 1-sided 95% confidence interval, 8.6%). Baseline characteristics
      and clinical outcomes were similar between patients with and without diabetes.
      The rate of probable or definite stent thrombosis was 0.9%. In conclusion, the 38
      mm length of the R-ZES was found to be safe and effective with a low rate of
      target lesion failure and stent thrombosis and no differences in outcomes between
      patients with and without diabetes.

PMID- 23953696
TI  - In-hospital major bleeding and its clinical relevance in patients with ST
      elevation myocardial infarction treated with primary percutaneous coronary
      intervention.
AB  - Advances in antithrombotic therapy for ST elevation myocardial infarction (STEMI)
      enhance the risk of bleeding. Therefore, the incidence, determinants, and
      prognostic implications of in-hospital major bleeding after primary percutaneous
      coronary intervention for STEMI were investigated. In 963 consecutive patients,
      the incidence of bleeding was evaluated according to commonly used
      classifications including Can Rapid risk stratification of Unstable angina
      patients Suppress Adverse outcomes with Early implementation of the ACC/AHA
      guidelines, Thrombolysis In Myocardial Infarction, Global Use of Strategies To
      Open coronary arteries, and Bleeding Academic Research Consortium. Multivariate
      regression analyses investigated determinants of bleeding and the relation
      between bleeding and 1-year all-cause mortality. Large variability in incidence
      existed depending on classification (1.3% to 21%). Female gender, heart rate,
      creatinine, multivessel disease, cardiogenic shock, and procedural failure were
      independently associated with bleeding. One-year mortality reached 10.2% in
      bleeders versus 2.0% in nonbleeders (p <0.001). Bleeding was independently
      associated with an increased risk of 1-year mortality (hazard ratio [HR] 2.41, p
      <0.017). Assessment of individual classifications confirmed the increased risk of
      mortality for Bleeding Academic Research Consortium (HR 2.27, p = 0.048), but not
      for Can Rapid risk stratification of Unstable angina patients Suppress Adverse
      outcomes with Early implementation of the ACC/AHA guidelines, Thrombolysis In
      Myocardial Infarction, and Global Use of Strategies To Open coronary arteries
      bleeding. Thrombotic events occurred more frequently in bleeders (5.8% vs 1.5%, p
      <0.001); however, bleeding remained independently related to mortality with a
      negligible reduction in HR (2.25, p = 0.028) after adjustment. In conclusion, in
      hospital major bleeding was frequently observed after STEMI, but a widespread
      variation in incidence existed depending on the applied definition. Patient and
      procedural characteristics were related to bleeding, allowing identification of
      high-risk patients. In-hospital major bleeding was independently associated with
      1-year all-cause mortality; however, not all bleeding classifications proved
      equally relevant to prognosis. The relation between bleeding and mortality was
      shown not to be driven by the higher rate of thrombotic events among bleeders.

PMID- 23953698
TI  - Transition of mesenchymal stem/stromal cells to endothelial cells.
AB  - Mesenchymal stem/stromal cells (MSCs) are heterogeneous. A fraction of these
      cells constitute multipotent cells that can self-renew and mainly give rise to
      mesodermal lineage cells such as adipocytes, osteocytes and chondrocytes. The
      ability of MSCs to differentiate into endothelial cells remains controversial.
      Isolation and in vitro manipulation of MSCs before clinical application are
      important steps. High numbers of MSCs are needed, requiring the in vitro
      expansion of these clinically important cells. To this end, a well-controlled
      procedure for MSC isolation and maintenance in culture is necessary. 

PMID- 23953697
TI  - Quantitative point-of-care troponin T measurement for diagnosis and prognosis in
      patients with a suspected acute myocardial infarction.
AB  - Improvement of prehospital triage is essential to ensure rapid management of
      patients with acute myocardial infarction (AMI). This study evaluates the
      feasibility of prehospital quantitative point-of-care cardiac troponin T (POC
      cTnT) analysis, its ability to identify patients with AMI, and its capacity to
      predict mortality. The study was performed in the Central Denmark Region from May
      2010 to May 2011. As a supplement to electrocardiography, a prehospital POC-cTnT
      measurement was performed by a paramedic in patients with suspected AMI. AMI was
      diagnosed according to the universal definition of myocardial infarction using
      the ninety-ninth percentile upper reference level as diagnostic cut point. The
      paramedics performed POC-cTnT measurements in 985 subjects with a symptom
      duration of 70 minutes (95% CI, 35 to 180); of whom, 200 (20%) had an AMI. The
      prehospital sample was obtained 88 minutes (range, 58 to 131) before the sample
      made on admission to the hospital. The sensitivity for detection of patients with
      an AMI was 39% (95% CI, 32% to 46%) and the diagnostic accuracy of the POC-cTnT
      values was 0.67 (95% CI, 0.64 to 0.71). Adjusted survival analysis showed a
      strong significant association between elevated prehospital POC-cTnT level above
      the detection level of 50 ng/L and mortality in patients with a suspected AMI
      irrespective of whether an AMI was diagnosed. In conclusion, large-scale
      quantitative prehospital POC-cTnT testing by paramedics is feasible. An elevated
      prehospital POC-cTnT value contains diagnostic information and is highly
      predictive of mortality in patients with a suspected AMI.

PMID- 23953699
TI  - Neurocognitive impairment in HIV-1-infected adults in Sub-Saharan Africa: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: To estimate the burden of HIV neurocognitive impairment (NCI) among
      adult patients on and off antiretroviral therapy (ART) in Sub-Saharan Africa.
      METHODS: Estimates were derived from a random effects meta-analysis of
      prospective studies reporting HIV status, utilization of ART, and the presence of
      NCI determined using the International HIV Dementia Scale. RESULTS: Sixteen
      studies with quality data from seven countries in Sub-Saharan Africa up to June
      2012 were included. Among HIV patients, the frequency of NCI pre-ART was 42.37%
      (95% confidence interval (CI) 32.18-52.56%), and among those on ART for >=6
      months was 30.39% (95% CI 13.17-47.61%). Respective NCI estimates in studies from
      Uganda were 46.49% (95% CI 30.62-62.37%) and 28.50% (95% CI -1.31-58.30%). NCI
      was more common among patients with a concomitant psychiatric ailment. HIV
      positive patients compared to HIV-negative controls were predisposed to NCI (odds
      ratio (OR) 6.49, 95% CI 1.68-25.08); the estimated unadjusted attributable risk
      of HIV infection leading to NCI was 85%. Meta-regression showed no associations
      between age, gender, CD4 cell counts, or years of education with NCI. Patients on
      ART were less likely to have NCI compared to HIV-infected pre-ART patients, with
      OR 0.36 (95% CI 0.19-0.69). In longitudinal studies with the same patients
      followed before and at >=6 months after ART, the OR of NCI after ART compared to
      pre-ART was 0.23 (95% CI 0.14-0.37). The combined burden of NCI among pre-ART and
      on-ART patients in Sub-Saharan Africa was estimated at 8,121,910 (95% CI
      5,772,140-10,471,680). No publication bias was observed, although residual
      confounding from differing environmental factors, stages of HIV infection, and
      viral clades might be a limitation. CONCLUSIONS: HIV strongly predisposes to NCI
      leading to a huge burden in Sub-Saharan Africa, and scale-up of ART can
      substantially reduce it.

PMID- 23953700
TI  - Anti-hepatitis E virus antibody prevalence in French expatriate workers.
AB  - OBJECTIVE: The hepatitis E virus (HEV) is a leading cause of acute hepatitis in
      developing countries and an emerging pathogen in Europe. HEV seroprevalence has
      rarely been assessed in cohorts of travelers, and previous studies have reported
      a very low rate of exposure. We assessed HEV seroprevalence in French expatriate
      workers. METHODS: The prevalence of HEV IgG and IgM was assessed among 43 French
      expatriate workers using two commercial microplate enzyme immunoassays (Adaltis
      and Wantai). Additionally HEV IgG-positive sera were tested with an immunoblot
      assay (recomLine), while IgM-positive sera were tested with a rapid
      immunochromatographic assay (Assure). RESULTS: The prevalence of anti-HEV IgG was
      3.7 times higher in French expatriates than in comparable blood donors from the
      same area. A discrepancy was evidenced between the HEV IgG results obtained by
      the Wantai and Adaltis assays (48.8% vs. 30.2%). CONCLUSIONS: Expatriation from
      France, including to areas not recognized as hyperendemic for HEV, may expose
      individuals to HEV infection. This issue warrants further study; in particular,
      serology should be compared before and after travel. The most sensitive Wantai
      serological assay should be used for epidemiological studies to obtain better
      insight into the epidemiology of HEV.

PMID- 23953701
TI  - Reproducibility of speckle-tracking-based strain measures of left ventricular
      function in a community-based study.
AB  - BACKGROUND: The reproducibility of echocardiographic measurements of myocardial
      strain, performed in a community-based setting, has not been reported previously.
      METHODS: The reproducibility of left ventricular strain measurements was examined
      in two samples of 20 participants each from the Offspring Cohort of the
      Framingham Heart Study (mean age, 63 +/- 9 years; 59% women). Two-dimensional
      speckle-tracking-based measurements of global peak left ventricular strain in
      systole were performed in the apical four-chamber, apical two-chamber, and
      midventricular parasternal short-axis views. RESULTS: Interobserver intraclass
      correlation coefficients were >=0.84 for all global strain measurements, with
      average coefficients of variation of <=4% for global longitudinal and
      circumferential strain and <8% for global transverse and radial strain. For left
      ventricular strain measurements performed in each of the three views,
      intraobserver intraclass correlation coefficients were >=0.91 among time points
      spanning a total 8-month period. The average coefficients of variation were <6%
      for global longitudinal and circumferential strain and <9% for global transverse
      and radial strain. Interobserver and intraobserver reproducibility findings were
      similar in analyses adjusting for frame rate. CONCLUSIONS: Excellent
      reproducibility of global longitudinal and circumferential strain measurements
      and very good reproducibility of global transverse and radial strain measurements
      were observed. Taken together, these findings demonstrate the reproducibility of
      performing echocardiographic strain measurements in a large, epidemiologic
      community-based setting.

PMID- 23953702
TI  - Effect of through-plane and twisting motion on left ventricular strain
      calculation: direct comparison between two-dimensional and three-dimensional
      speckle-tracking echocardiography.
AB  - BACKGROUND: The aim of this study was to investigate the effect of out-of-plane
      motion on discrepancies in strain measurements between two-dimensional (2D) and
      three-dimensional (3D) echocardiography. METHODS: Two-dimensional and 3D data
      sets were acquired in 54 patients. Using 2D and 3D speckle-tracking software,
      global circumferential strain (CS) and longitudinal strain (LS) as well as CS and
      LS at three left ventricular (LV) levels was measured. The effect of through
      plane motion was assessed by mitral annular displacement. RESULTS: Although a
      good correlation of global CS was noted between the two methods (r = 0.80, P <
      .01), mean values of global CS were significantly higher on 3D compared with 2D
      echocardiography. Correlations of CS and their mean differences were 0.65 and 
      4.61 at the basal level, 0.76 and -4.17 at the midventricular level, and 0.60 and
      -2.23 at the apical level, respectively. Correlation of global CS between the two
      methods was higher in patients who showed mitral annular displacement < 9.4 mm (r
      = 0.81) compared with those with mitral annular displacement >= 9.4 mm (r =
      0.61). A good correlation of global LS (r = 0.89, P < .01) was noted, with no
      significant bias. Correlations of LS and their mean differences were 0.52 and
      1.59 at the basal level, 0.89 and -1.17 at the midventricular level, and 0.73 and
      1.46 at the apical level, respectively. Correlation of LS between the two methods
      was higher in patients who showed LV twist < 12.2 degrees  (r = 0.94) compared
      with patients with LV twist >= 12.2 degrees  (r = 0.68). CONCLUSIONS: Through
      plane motion produced discrepancies in CS measurements, especially at the LV
      basal level. Larger bias of LS at the basal and apical LV levels compared with
      the midventricular level between the two methods suggests that LV twisting also
      affects the calculation of 2D LS.

PMID- 23953703
TI  - Novel pathogenetic mechanisms and structural adaptations in ischemic mitral
      regurgitation.
AB  - Ischemic mitral regurgitation (MR) is a common complication of myocardial
      infarction thought to result from leaflet tethering caused by displacement of the
      papillary muscles that occurs as the left ventricle remodels. The author explores
      the possibility that left atrial remodeling may also play a role in the
      pathogenesis of ischemic MR, through a novel mechanism: atriogenic leaflet
      tethering. When ischemic MR is hemodynamically significant, the left ventricle
      compensates by dilating to preserve forward output using the Starling mechanism.
      Left ventricular dilatation, however, worsens MR by increasing the mitral valve
      regurgitant orifice, leading to a vicious cycle in which MR begets more MR. The
      author proposes that several structural adaptations play a role in reducing
      ischemic MR. In contrast to the compensatory effects of left ventricular
      enlargement, these may reduce, rather than increase, its severity. The suggested
      adaptations involve the mitral valve leaflets, the papillary muscles, the mitral
      annulus, and the left ventricular false tendons. This review describes the
      potential role each may play in reducing ischemic MR. Therapies that exploit
      these adaptations are also discussed. 

PMID- 23953704
TI  - Reference and normalization methods: essential tools for the intercomparison of
      NMR spectra.
AB  - This review aims at providing an analysis of the various available reference
      methods in nuclear magnetic resonance, based on recent literature. This paper
      will provide a tool to help users in choosing the appropriate method depending on
      the NMR experiment, sample and targeted application. For each method, the crucial
      parameters that should be particularly considered to reach the accuracy
      objectives of quantitative NMR are described. After defining the main concepts,
      the principle, the analytical performance and the main recent applications of
      each method are described, and a critical discussion is finally provided. 

PMID- 23953705
TI  - New trends in LC protein ligand screening.
AB  - The diversity of small molecules available to produce truly innovative drugs
      associated with the wealth of known biological targets calls for key strategies
      in protein ligand screening. This review encompasses the recently developed
      bioaffinity-based strategies. A critical view of the use of zonal, frontal, and
      nonlinear chromatography with immobilized proteins is given. The association of
      these elution modes with the ligand fishing method, which uses nanomagnetics
      particles, is also addressed. A series of applications and how these new
      screening strategies can be used to determine the function, affinity, and
      activity parameters of proteins is discussed. 

PMID- 23953706
TI  - The performance of the Finnish Diabetes Risk Score, a modified Finnish Diabetes
      Risk Score and a simplified Finnish Diabetes Risk Score in community-based cross
      sectional screening of undiagnosed type 2 diabetes in the Philippines.
AB  - AIM: The performance of the Finnish Diabetes Risk Score (FINDRISC) and 2
      modifications in community screening for undiagnosed type 2 diabetes (UDD) in the
      Philippines was evaluated. METHODS: Active community-based screening for diabetes
      was conducted where FINDRISC assessment was done. Modified (modFINDRISC) and
      simplified (simpFINDRISC) versions were rendered based on Asian standards, study
      results, and local context. Diabetes was diagnosed through 2 separate blood
      glucose tests. Areas under the receiver operating characteristic curve (ROC-AUC)
      and statistics for diagnostic tests for FINDRISC and the modifications were
      analyzed. RESULTS: Complete data was collected from 1752 people aged 20-92; 8.6%
      tested positive for diabetes. ROC-AUC for UDD were 0.738 (FINDRISC), 0.743
      (modFINDRISC) and 0.752 (simpFINDRISC). The differences between the FINDRISC and
      the modifications were not statistically significant (p=0.172). CONCLUSIONS: The
      performance of all 3 risk score calculators in the screening for UDD in the
      Philippines was good and may be useful in populations having similar
      characteristics. Considering the setting and resource constraints, the
      simpFINDRISC is preferred.

PMID- 23953707
TI  - Safety and effectiveness of biphasic insulin aspart 30 in people with type 2
      diabetes switching from basal-bolus insulin regimens in the A1chieve study.
AB  - AIMS: Biphasic insulin aspart 30 allows fewer daily injections versus basal-bolus
      insulin regimens, which may improve adherence and treatment outcome. This sub
      analysis of the observational A1chieve study assessed clinical safety and
      effectiveness of biphasic insulin aspart 30 in people with type 2 diabetes
      previously receiving basal-bolus insulin regimens. METHODS: A1chieve was an
      international, open-label, 24-week study in people with type 2 diabetes
      starting/switching to biphasic insulin aspart 30, insulin detemir or insulin
      aspart. This sub-analysis assessed patients switching from insulin glargine- or
      neutral protamine Hagedorn insulin-based basal-bolus insulin regimens to biphasic
      insulin aspart 30. RESULTS: 1024 patients were included. At 24 weeks, glycated
      haemoglobin and fasting plasma glucose were significantly reduced from baseline
      in both cohorts (all p<0.001). The proportion reporting any hypoglycaemia, major
      hypoglycaemia or nocturnal hypoglycaemia was significantly reduced after 24 weeks
      (all p<0.05). No serious adverse drug reactions were reported. Both cohorts had
      significantly improved health-related quality of life (HRQoL; p<0.001).
      CONCLUSIONS: 24 weeks after switching from basal-bolus insulin regimens to
      biphasic insulin aspart 30, glycaemic control and HRQoL were significantly
      improved, and hypoglycaemia was significantly reduced. This suggests that people
      with type 2 diabetes inadequately controlled on basal-bolus insulin regimens can
      consider biphasic insulin aspart 30.

PMID- 23953708
TI  - Family history of malignant neoplasm and its relation with clinicopathologic
      features of gastric cancer patients.
AB  - BACKGROUND: Few studies to date have evaluated gastric cancer(GC)-related
      malignant neoplasm family history (MN-FH), and their findings have been largely
      inconsistent. The aim of this study is to evaluate the prevalence of MN-FH and
      its relation to the clinicopathologic features of GC. METHODS: A total of 104
      hospitalized patients with primary gastric adenocarcinoma was prospectively
      analyzed from 2008 to 2009. Positive MN-FH was defined as MN-affected first- and
      second-degree relatives of the current GC cases. The relation between prevalence
      of positive MN-FH and clinicopathologic features in the current GC patients was
      assessed using the Chi-square test with Cramer's V coefficient. RESULTS: Thirty
      seven (35.6%) of the GC patients had positive MN-FH, with 42 associated tumors in
      first- and second-degree relatives. Twenty-six (61.9%) of the associated tumors
      were located in the digestive system, including the esophagus (26.2%), stomach
      (23.8%), liver (9.5%) and colon (2.4%). Lung cancers were the most prevalent non
      digestive system-associated tumors (9.5%). Correlation analysis revealed no
      significant relations with prevalence of MN-FH and any of the clinicopathologic
      features (all, P > 0.05), including sex (V = 0.044), age (V = 0.060) and
      histological subtypes (V = 0.109). CONCLUSIONS: More than one-third of the GC
      patients in our hospital had positive MN-FH. The most frequent forms of MN-FH
      were esophageal cancer and GC. The prevalence of positive MN-FH was not
      correlated to any of the clinicopathologic features, including sex, age and
      histological subtypes in the study population of GC patients.

PMID- 23953709
TI  - Antagonistic effect of the inflammasome on thymic stromal lymphopoietin
      expression in the skin.
AB  - BACKGROUND: Innate immune sensors control key cytokines that regulate T-cell
      priming and T-cell fate. This is particularly evident in allergic reactions,
      which represent ideal systems to study the interplay of innate and adaptive
      immunity. In patients with contact dermatitis, inflammasome-mediated IL-1
      activation is responsible for a TH1 immune response. Surprisingly, the IL-1
      signaling pathway was also proposed to control the activation of thymic stromal
      lymphopoietin (TSLP), a cytokine implicated in development of the T(H)2 response
      in patients with atopic dermatitis (AD) and asthma. OBJECTIVES: We sought to
      assess the effect of the inflammasome on TSLP expression levels and the
      development of AD. METHODS: We studied the effect of the inflammasome activator
      2,4-dinitrofluorobenzene, and IL-1beta on TSLP mRNA expression levels in mouse
      and human cell lines (in vitro assays), as well as in live mice and on human skin
      transplants. We also assessed the effect of 2,4-dinitrofluorobenzene on TSLP and
      the TH2 response in mice in which the inflammasome and IL-1 signaling pathways
      were blocked, either genetically or pharmacologically, in 2 models of AD.
      RESULTS: We provide in vitro and in vivo evidence that inflammasome activation
      has an inhibitory role on TSLP mRNA expression and T(H)2 cell fate in the skin.
      We also show that solvents influence the activation of TSLP and IL-1beta and
      direct the T-cell fate to a given hapten. CONCLUSION: Our observations strongly
      suggest that the TH1 versus TH2 cell fate decision is regulated at multiple
      levels and starts with innate immune events occurring within peripheral
      epithelial tissues.

PMID- 23953710
TI  - Real-time differential tracking of human neutrophil and eosinophil migration in
      vivo.
AB  - BACKGROUND: Hitherto, in vivo studies of human granulocyte migration have been
      based on indiscriminate labeling of total granulocyte populations. We
      hypothesized that the kinetics of isolated human neutrophil and eosinophil
      migration through major organs in vivo are fundamentally different, with the
      corollary that studying unseparated populations distorts measurement of both.
      METHODS: Blood neutrophils and eosinophils were isolated on 2 separate occasions
      from human volunteers by using Current Good Manufacturing Practice CD16 CliniMACS
      isolation, labeled with technetium 99m-hexamethylpropyleneamine oxime, and then
      reinfused intravenously. The kinetics of cellular efflux were imaged over 4
      hours. RESULTS: Neutrophils and eosinophils were isolated to a mean purity of
      greater than 97% and greater than 95%, respectively. Activation of neutrophils
      measured as an increase in their CD11b mean fluorescence intensity in whole blood
      and after isolation and radiolabeling was 25.98 +/- 7.59 and 51.82 +/- 17.44,
      respectively, and was not significant (P = .052), but the mean fluorescence
      intensity of CD69 increased significantly on eosinophils. Analysis of the
      scintigraphic profile of lung efflux revealed exponential clearance of
      eosinophils, with a mean half-life of 4.16 +/- 0.11 minutes. Neutrophil efflux
      was at a significantly slower half-life of 13.72 +/- 4.14 minutes (P = .009). The
      migration of neutrophils and eosinophils was significantly different in the
      spleen at all time points (P = .014), in the liver at 15 minutes (P = .001), and
      in the bone marrow at 4 hours (P = .003). CONCLUSIONS: The kinetics of migration
      of neutrophils and eosinophils through the lung, spleen, and bone marrow of human
      volunteers are significantly different. Study of mixed populations might be
      misleading.

PMID- 23953712
TI  - A safe, effective, and facility compatible cleaning in place procedure for
      affinity resin in large-scale monoclonal antibody purification.
AB  - Cleaning-in-place (CIP) for column chromatography plays an important role in
      therapeutic protein production. A robust and efficient CIP procedure ensures
      product quality, improves column life time and reduces the cost of the
      purification processes, particularly for those using expensive affinity resins,
      such as MabSelect protein A resin. Cleaning efficiency, resin compatibility, and
      facility compatibility are the three major aspects to consider in CIP process
      design. Cleaning MabSelect resin with 50mM sodium hydroxide (NaOH) along with 1M
      sodium chloride is one of the most popular cleaning procedures used in
      biopharmaceutical industries. However, high concentration sodium chloride is a
      leading cause of corrosion in the stainless steel containers used in large scale
      manufacture. Corroded containers may potentially introduce metal contaminants
      into purified drug products. Therefore, it is challenging to apply this cleaning
      procedure into commercial manufacturing due to facility compatibility and drug
      safety concerns. This paper reports a safe, effective and environmental and
      facility-friendly cleaning procedure that is suitable for large scale affinity
      chromatography. An alternative salt (sodium sulfate) is used to prevent the
      stainless steel corrosion caused by sodium chloride. Sodium hydroxide and salt
      concentrations were optimized using a high throughput screening approach to
      achieve the best combination of facility compatibility, cleaning efficiency and
      resin stability. Additionally, benzyl alcohol is applied to achieve more
      effective microbial control. Based on the findings, the recommended optimum
      cleaning strategy is cleaning MabSelect resin with 25 mM NaOH, 0.25 M Na2SO4 and
      1% benzyl alcohol solution every cycle, followed by a more stringent cleaning
      using 50 mM NaOH with 0.25 M Na2SO4 and 1% benzyl alcohol at the end of each
      manufacturing campaign. A resin life cycle study using the MabSelect affinity
      resin demonstrates that the new cleaning strategy prolongs resin life time and
      consistently delivers high purity drug products.

PMID- 23953711
TI  - Polymorphism in cathelicidin gene (CAMP) that alters Hypoxia-inducible factor
      (HIF-1alpha::ARNT) binding is not associated with tuberculosis.
AB  - Polymorphisms in the CAMP gene (cathelicidin) have not been tested in
      tuberculosis susceptibility. We tested polymorphisms rs9844812 (HIF-1alpha::ARNT
      binding site) and rs56122065 (CAMP) plus rs1800972 (DEFB1). SNP rs1800972 was
      associated with extrapulmonary tuberculosis (EPTB) in a codominant model
      (genotype CG, P = 0.037, OR 4.82; 95% CI: 0.92-47.42; statistical power, 82%),
      but not PTB (P = 0.101) in a Mexican population. 

PMID- 23953713
TI  - Ampholine-functionalized hybrid organic-inorganic silica material as sorbent for
      solid-phase extraction of acidic and basic compounds.
AB  - A novel sorbent for solid-phase extraction (SPE) was synthesized by chemical
      immobilization of ampholine on hybrid organic-inorganic silica material. The
      ampholine-functionalized hybrid organic-inorganic silica sorbent is consisted of
      aliphatic amine groups, carboxyl groups and long carbon chains, allowing for
      extraction of both acidic and basic compounds. The retention properties of the
      developed sorbent were evaluated for 1-hydroxy-2-naphthoic acid (HNA), 1
      naphthoic acid (NA), 3-hydroxybenzoic acid (HBA), benzoic acid (BA), sorbic acid
      (SA), vanillic aldehyde (VA), butyl 4-hydroxybenzoate (BHB), propyl 4
      hydroxybenzoate (PHB), ethyl 4-hydroxybenzoate (EHB), and methyl 4
      hydroxybenzoate (MHB). The results show that such a sorbent has three types of
      interaction, i.e., electrostatic interaction, hydrophobic interaction, and
      hydrogen bonding, exhibiting high extraction efficiency towards the compounds
      tested. The adsorption capacities of the analytes ranged from 0.61 to 6.54MUgmg(
      1). The reproducibility of the sorbent preparation was evaluated at three spiking
      concentration levels, with relative standard deviations (RSDs) of 1.0-10.5%. The
      recoveries of ten acidic and basic compounds spiked in beverage Coca-Cola((r))
      sample ranged from 82.5% to 98.2% with RSDs less than 5.8%. Under optimum
      conditions, the ampholine-functionalized hybrid organic-inorganic silica sorbent
      rendered higher extraction efficiency for acidic compounds than that of the
      commercially available ampholine-functionalized silica particles, and was
      comparable to that of the commercial Oasis WAX and Oasis WCX.

PMID- 23953714
TI  - Quantitative high-performance liquid chromatography-tandem mass spectrometry
      method for the analysis of free desmosines in plasma and urine.
AB  - A rapid method for the determination of the sum of free desmosine and
      isodesmosine in human plasma and urine is described. Efficient sample clean-up
      prior to LC-MS/MS analysis is mandatory for detection of free desmosines in
      plasma samples. The combination of ultra-filtration and a two-step solid phase
      extraction minimizes the sample complexity and ion suppression effects. The flow
      through from the ultra filtration is passed through a C18 resin and then the
      target analytes are trapped and enriched on a mixed mode solid phase extraction
      material. The combination of these three orthogonal sample preparation steps
      allows detection of endogenous free desmosines in plasma from healthy
      individuals. An analytical column packed with porous graphitic carbon material
      enables the retention of the polar desmosine analytes, which are measured by
      electrospray ionization tandem mass spectrometry. Deuterium labeled isodesmosine
      is added as internal standard and a linear calibration curve was constructed in
      the range of 0.1-2.0 nmol/L for plasma samples and 5-200 nmol/L for urine
      samples. These results demonstrate that the described LC-MS/MS method provides
      sensitive, repeatable and accurate quantification of free desmosines in plasma
      and urine samples.

PMID- 23953715
TI  - Rapid and sensitive profiling of tear wax ester species using high performance
      liquid chromatography coupled with tandem mass spectrometry.
AB  - A rapid and sensitive method was developed for quantitative profiling of wax
      esters (WEs) in human tear lipidome. Individual WE species was separated by
      liquid chromatography and detected by electrospray ionisation mass spectrometry
      using specific multiple reaction monitoring (MRM) scanning. Palmitoyl palmitate
      and in-house synthesized wax esters (13)C18:1(oleic acid-1,2,3,7,8,9,10
      (13)C7)C26:0 were used as internal standards for quantitation of WEs containing
      saturated and unsaturated fatty acids (FA), respectively. The limit of detection
      was approximately 70 nmol/L. The linearity range of the liquid chromatography
      (LC)-MRM detection for WEs was about three orders of magnitude. Quantitative
      analyses of 141 individual WE in the human tear lipidome demonstrated that
      species comprising FA18:1 and FA16:1 each accounted for 47.7% and 24.0% (molar%)
      of total WE, while fatty alcohols in WEs of human tears ranged from 17 carbons to
      32 carbons with predominant species represented by C24, C25 and C26.

PMID- 23953717
TI  - Discussion.

PMID- 23953716
TI  - A prospective study of growth and rupture risk of small-to-moderate size
      ascending aortic aneurysms.
AB  - OBJECTIVE: The natural history of small-to-moderate size ascending aortic
      aneurysms is poorly understood. To follow these patients better, we have
      developed a method to objectively and reproducibly measure ascending aortic
      volume on the basis of gated contrast computed tomography scans. METHODS: From
      2009 to 2011, 507 patients were referred for management of ascending aortic
      aneurysms. A total of 232 patients (46%) with small-to-moderate size aneurysms
      who did not have compelling indications for operation had measurement(s) of
      ascending aortic and total aortic volume; 166 patients had more than 1 scan,
      allowing measurement of growth. A total of 66 patients admitted to the emergency
      department without ascending aortic pathology served as a reference group.
      RESULTS: None of the patients experienced rupture, dissection, or death; 3
      patients ultimately underwent operation. Ascending aortic volume and volume/total
      aortic volume differed for the surveillance and reference groups: 132.8 +/- 39.4
      mL versus 78.0 +/- 24.5 mL; 38.3% +/- 7.4% versus 29.1% +/- 3.9%, respectively
      (both P < .001). Diameters at the sinotubular junction and mid-ascending aortic
      were 4.1 +/- 0.6 cm and 4.4 +/- 0.6 cm, respectively, for the surveillance group
      and 3.0 +/- 0.4 cm and 3.2 +/- 0.4 cm, respectively, for controls. The increase
      in ascending aortic volume was 0.95 +/- 4.5 mL/year and 0.73% +/- 3.7%/year (P =
      .007 and .012, respectively). Analysis of risk factors for ascending aortic
      growth revealed only the use of antithrombotic medication as possibly
      significant. CONCLUSIONS: Computed tomography volume measurements provide an
      objective method for ascertaining aortic size and monitoring expansion. Patients
      with small-to-moderate ascending aortic aneurysms who are carefully followed and
      managed appropriately have slow aneurysm growth and a small risk of rupture or
      dissection. Annual computed tomography screening may not be indicated, and
      elective resection-absent other surgical indications-is not necessary. The
      rupture/dissection risk for even larger aneurysms in carefully followed patients
      may be lower than currently believed.

PMID- 23953718
TI  - Pulmonary sleeve resection in locally advanced lung cancer using cryopreserved
      allograft for pulmonary artery replacement.
AB  - BACKGROUND: During lobectomy, resection of pulmonary artery, followed by
      reconstruction or replacement with or without concomitant sleeve bronchial
      resection, is feasible in selected cases. We report morbidity, mortality, and
      technical issues in pulmonary artery replacement using a cryopreserved arterial
      allograft after sleeve resection for centrally located non-small cell lung
      carcinoma (NSCLC). METHODS: We reviewed clinical and pathologic data of patients
      who underwent arterial sleeve lobectomy with pulmonary artery replacement in our
      institution from 2007 to 2012. RESULTS: Of 178 centrally located NSCLCs, sleeve
      resections were performed in 92 (51%), pneumonectomies in 33 (18%), and
      lobectomies in 53 (31%). Of the 32 (34.7%) pulmonary) reconstructions (excluding
      tangential suture), 20 (21.7%) were end-to-end anastomosis, 2 (2.1%) were
      pericardial patch reconstructions, and 10 (11%) were PA replacements. Clinical T
      staging was cT2a in 4 patients, cT2b in 3, cT3 in 2, and cT4 in 1. Four patients
      received concurrent induction chemoradiotherapy. Three patients underwent a
      double-sleeve right lobectomy. Cryopreserved allografts used were descending
      thoracic aorta (n = 3) and pulmonary arteries (n = 7). Complete resection (R0)
      was achieved in all patients. Final N staging was pN0 (n = 4), pN1 (n = 5), and
      pN2 (n = 1). There was no operative mortality. Four patients had major morbidity,
      including 1 early conduit thrombosis treated by pneumonectomy completion. Graft
      patency, assessed by contrast-enhanced computed tomography scan, was 90%. Mean
      follow-up was 25 +/- 14 (range, 8-47) months (30% for >36 months). Overall 5-year
      survival was 66.7%, and the estimated median disease-free survival was 42 months.
      CONCLUSIONS: In central NSCLCs, conservative surgery using a cryopreserved
      arterial allograft to replace the pulmonary artery after extended segmental
      resection could avoid pneumonectomy in selected patients.

PMID- 23953719
TI  - Discussion.

PMID- 23953720
TI  - Transformation of percutaneous venoarterial extracorporeal membrane oxygenation
      access to a safe peripheral arterial cannulation.

PMID- 23953721
TI  - Protecting the aged heart during cardiac surgery: use of del Nido cardioplegia
      provides superior functional recovery in isolated hearts.
AB  - OBJECTIVES: Aged hearts are particularly vulnerable to ischemia-reperfusion
      injury. Our objective was to determine if del Nido cardioplegia, which contains
      lidocaine, less blood, and less calcium than our standard cardioplegia, provides
      superior protection for aged hearts. We also sought to determine if the lidocaine
      in del Nido cardioplegia is adequate to prevent Na(+) influx via the window
      current. METHODS: Sodium channel kinetics were measured in rat cardiomyocytes
      with and without lidocaine. Recovery after 60 minutes of cardioplegic arrest was
      assessed in isolated working senescent rat hearts. Del Nido cardioplegia was
      delivered as a single dose (n = 8) because it is used clinically, and standard
      cardioplegia was delivered as an induction dose with re-dosing every 20 minutes
      (n = 8). After 20 minutes of reperfusion, hearts were switched to working mode
      for 60 minutes. Flows were indexed to ventricular dry weight. Troponin release
      was assayed. RESULTS: Sodium channel kinetics indicated that the lidocaine
      concentration in del Nido cardioplegia minimizes the potential for Na+ influx via
      the window current. Spontaneous contractions occurred in fewer hearts arrested
      with del Nido cardioplegia (88% vs 13%; P = .01), and troponin release was
      reduced (0.24 vs 0.89 ng/mL; P = .017). Cardiac output was approximately 90% of
      baseline in the del Nido group compared with approximately 50% in the standard
      group (173 +/- 14 vs 86 +/- 22 mL . min(-1) . g(-1); P = .0008). Stroke work was
      higher in the del Nido group (93 +/- 6 vs 41 +/- 10 mL . mm Hg . g(-1); P =
      .0002). CONCLUSIONS: Del Nido cardioplegia prevents spontaneous contractions
      during arrest, reduces troponin release, and results in superior myocardial
      function in isolated aged hearts. Del Nido cardioplegia has the potential to
      provide superior myocardial protection for older patients undergoing cardiac
      surgery.

PMID- 23953722
TI  - Visual prostheses for the blind.
AB  - After more than 40 years of research, visual prostheses are moving from the
      laboratory into the clinic. These devices are designed to provide prosthetic
      vision to the blind by stimulating localized neural populations in one of the
      retinotopically organized structures of the visual pathway - typically the retina
      or visual cortex. The long gestation of this research reflects the many
      significant technical challenges encountered including surgical access,
      mechanical stability, hardware miniaturization, hermetic encapsulation, high
      density electrode arrays, and signal processing. This review provides an
      introduction to the pathophysiology of blindness; an overview of existing visual
      prostheses, their advantages and drawbacks; the perceptual effects evoked by
      electrical stimulation; as well as the role played by plasticity and training in
      clinical outcomes. 

PMID- 23953723
TI  - Hemophagocytic lymphohistiocytosis: advances in pathophysiology, diagnosis, and
      treatment.

PMID- 23953724
TI  - Diabetic ketoacidosis at diagnosis in Austrian children: a population-based
      analysis, 1989-2011.
AB  - OBJECTIVE: To analyze the effect of a community-based, poster-focused prevention
      program on the frequency of diabetic ketoacidosis (DKA) at diabetes onset in
      Austria. STUDY DESIGN: All newly diagnosed patients with diabetes <= 15 years of
      age were registered prospectively by the Austrian Diabetes Incidence Study Group.
      Registered data included initial blood glucose, pH, and ketonuria. DKA was
      defined as pH < 7.3 and severe DKA as pH < 7.1. Data between 1989 and 2011 were
      available. In autumn, 2009, a community-based prevention program similar to the
      Parma Campaign, in which posters were dispensed broadly, was initiated. The
      frequency of DKA at the onset of diabetes in the years 2005-2009 and 2010-2011
      was compared. RESULTS: During the study period, 4038 children were registered. A
      total of 37.2% presented with DKA; 26% had a mild and 11.2% a severe form. The
      frequency of DKA was negatively associated with age at onset. In the years before
      the intervention program, 26% had mild DKA compared with 27% after the
      intervention (not significant). The prevalence of severe DKA in the years before
      the campaign was 12% compared with 9.5% thereafter (not significant). No
      significant change in the DKA rate at onset by the prevention program could be
      found when we compared age groups <5, 5 to <10, and 10 to <15 years, neither for
      mild nor for severe DKA. CONCLUSION: The frequency of DKA in children with newly
      diagnosed type 1 diabetes in Austria is high and did not change despite the
      efforts of a community-based information program.

PMID- 23953725
TI  - Patterns of clinical management of atopic dermatitis in infants and toddlers: a
      survey of three physician specialties in the United States.
AB  - OBJECTIVE: To describe atopic dermatitis (AD) management patterns in children
      <=36 months old as reported by pediatricians, dermatologists, and allergists in
      the US. STUDY DESIGN: A nationally-representative survey was administered to
      pediatricians (n = 101), dermatologists (n = 26), and allergists (n = 26). Main
      outcomes included referrals to health care professionals, suggested/ordered
      laboratory tests, management approach (dietary, pharmacologic, or combination of
      both) by age, AD location, and severity. RESULTS: Significant differences were
      observed in referrals to healthcare professionals (P < .001). Pediatricians more
      frequently referred to dermatologists than allergists in mild (52.4% vs 32.0%)
      and moderate/severe (60.6% vs 38.1%) cases. Dermatologists referred to allergists
      less frequently for mild (9.1%) than moderate/severe (40.7%) AD cases.
      Pediatricians (59%), allergists (61.5%), and dermatologists (26.9%) reported
      treating at least some of their patients with AD with dietary management (infant
      formula change) alone (with or without emollients). Soy-based formulas were often
      used. For mild AD, the most commonly reported first-line pharmacologic treatments
      included topical emollients, topical corticosteroids, and barrier repair topical
      therapy/medical devices. Over 80% of physicians used a dietary and pharmacologic
      combination approach. Dermatologists were most likely to manage AD symptoms with
      a pharmacologic-only approach. AD lesion location influenced pharmacologic
      treatment in >80% of physicians. CONCLUSIONS: Significant and distinct
      differences in AD treatment approach exist among physicians surveyed. Most
      pediatricians and allergists use formula change as a management strategy in some
      patients, whereas dermatologists favor a pharmacologic approach. This diversity
      may result from inadequate evidence for a standard approach. Consistent methods
      for managing AD are needed.

PMID- 23953726
TI  - Autophagic kinases SmVPS34 and SmVPS15 are required for viability in the
      filamentous ascomycete Sordaria macrospora.
AB  - Autophagy is a tightly controlled degradation process of all eukaryotes. It
      includes the sequestration of cytoplasmic contents and organelles within a double
      membraned autophagosome. Autophagy involves core autophagy related (atg) genes as
      well as genes regulating vesicle trafficking. Previously, we analyzed the impact
      of proteins of the core autophagic machinery SmATG7, SmATG8 and SmATG4 on the
      sexual and vegetative development of the filamentous ascomycete Sordaria
      macrospora. While deletion of Smatg8 and Smatg4 abolished fruiting-body formation
      and impaired vegetative growth, Smatg7 is required for viability. In yeast, the
      phosphatidylinositol 3-kinase vacuolar protein sorting 34 (Vps34) and its
      myristoylated membrane targeting unit, the protein kinase Vps15 have been shown
      to be important regulators of autophagy and vacuolar protein sorting. However,
      their exact role in filamentous ascomycetes remains elusive. To determine the
      function of Smvps34 and Smvps15 we isolated genes with high sequence similarity
      to Saccharomyces cerevisiae VPS34 and VPS15. For both genes we were not able to
      generate a homokaryotic knockout mutant in S. macrospora, suggesting that Smvps34
      and Smvps15 are required for viability. Furthermore, we analyzed the repertoire
      of vps genes encoded by S. macrospora and could identify putative homologs of
      nearly all of the 61 VPS genes of S. cerevisiae. 

PMID- 23953727
TI  - Fibroblasts express OvHV-2 capsid protein in vasculitis lesions of American bison
      (Bison bison) with experimental sheep-associated malignant catarrhal fever.
AB  - American bison (Bison bison) are particularly susceptible to developing fatal
      sheep-associated malignant catarrhal fever (SA-MCF) caused by ovine herpesvirus-2
      (OvHV-2), a gamma-herpesvirus in the Macavirus genus. This generally fatal
      disease is characterized by lymphoproliferation, vasculitis, and mucosal
      ulceration in American bison, domestic cattle (Bos taurus), and other clinically
      susceptible species which are considered non-adapted, dead-end hosts. The
      pathogenesis and cellular tropism of OvHV-2 infection have not been fully
      defined. An earlier study detected OvHV-2 open reading frame 25 (ORF25)
      transcripts encoding the viral major capsid protein in tissues of bison with SA
      MCF, and levels of viral transcript expression positively correlated with lesion
      severity. To further define the cellular tropism and replication of OvHV-2
      infection in vascular lesions of bison, immunofluorescence studies were performed
      to identify cell type(s) expressing ORF25 protein within tissues. Cytoplasmic and
      not nuclear ORF25 protein was demonstrated in predominantly perivascular
      fibroblasts in six bison with experimentally-induced SA-MCF, and there was no
      evidence of immunoreactivity in vascular endothelium, smooth muscle, or
      infiltrating leukocytes. The cytoplasmic distribution of viral major capsid
      protein suggests that viral replication in perivascular fibroblasts may be
      abortive in this dead-end host. These findings provide a novel foundation for
      defining the pathogenesis of vasculitis in non-adapted hosts with SA-MCF. 

PMID- 23953728
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration for
      differentiating N0 versus N1 lung cancer.
AB  - BACKGROUND: The aim of this study was to assess the value of endobronchial
      ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for
      differentiating cN0 versus cN1 non-small cell lung cancer. METHODS: A
      retrospective review of EBUS-TBNA results in patients with potentially resectable
      clinical N0 or N1 non-small cell lung cancer based on computed tomography and
      positron emission tomography was performed. Systematic mediastinal and hilar
      lymph node sampling was performed by EBUS-TBNA. Lymph nodes larger than 5 mm in
      short axis or suspicious nodes were targeted. In the absence of N2 or N3 disease,
      patients underwent resection with lymph node dissection. RESULTS: A total of 981
      patients underwent EBUS-TBNA during the study period, of which 163 patients met
      the study criteria. There were 94 cN0 and 69 cN1 patients. A total of 453 lymph
      nodes (338 mediastinal and 115 N1 lymph nodes, average 2.8 nodes/patient) were
      sampled. Endobronchial ultrasound upstaged 9 (5.5%) patients to N2 disease, but
      was falsely negative in the mediastinum in 7 (4.3%) patients. In cN0 patients,
      EBUS confirmed N0 in 87 (53.4%) and upstaged in 7 (4.3%, N1 in 1, N2 in 6). In
      cN1 patients, EBUS confirmed N1 in 19 (11.7%), downstaged in 47 (28.8%), and
      upstaged in 3 (1.8%). The sensitivity, specificity, diagnostic accuracy, and
      negative predictive value of EBUS-TBNA to accurately differentiate between N0 and
      N1 disease was 76.2%, 100%, 96.6%, and 96.2%, respectively. The accuracy of
      mediastinal staging was 95.7%. CONCLUSIONS: Endobronchial ultrasound-guided
      transbronchial needle aspiration can accurately access the hilar and interlobar
      lymph nodes in patients with potentially resectable lung cancer. Accurate
      assessment of cN0 versus cN1 by EBUS-TBNA may be used to guide induction therapy
      before surgery.

PMID- 23953729
TI  - Combined effects of sample parameters on polymer charging due to electron
      irradiation: a contour simulation.
AB  - Combined effects of sample parameters on polymer charging due to electron
      irradiation are explored by a novel approach of contour in parallel computing.
      Transient processes of negative charging of a Kapton film sample irradiated by 10
      keV electrons are simulated with a simultaneous scattering-transport model and
      the existing experimental secondary electron current. As a function of sample
      thickness and electron mobility, the contour maps are then presented of the
      steady-state leakage current and surface potential and the total charge
      accumulated in a charging process. It is found that the leakage current and
      surface potential behave similarly in the contour form, and the total charge has
      the local maximum with respect to the sample thickness. Generally, the sample
      thickness affects the charging process more than the electron mobility, but both
      have less influence in very strong and weak charging states. Accompanied by
      discussion of charge dissipation effects, this study offers a comprehensive
      insight into complicated charging phenomena in electron-based surface microscopy,
      analysis and measurement.

PMID- 23953731
TI  - C1 lateral mass screw placement via the posterior arch: a technique comparison
      and anatomic analysis.
AB  - BACKGROUND CONTEXT: Instrumentation of C1 is becoming increasingly common.
      Starting points initially described for C1 lateral mass screws at the lateral
      mass/posterior arch junction are technically challenging. Recently, a number of
      techniques have evolved advocating varying starting points and trajectories.
      Despite being technically easier, there are new safety concerns. Insufficient
      evidence exists for optimal C1 lateral mass screw placement with starting points
      in the posterior arch. PURPOSE: To determine anatomic variability of the C1
      lateral mass and posterior ring and to compare safety and feasibility of C1
      lateral mass screw placement techniques via the posterior arch. STUDY DESIGN:
      Descriptive anatomy for surgical technique. METHODS: One hundred thin-cut
      cervical spine computed tomography scans were acquired and formatted for virtual
      surgery. Four different described techniques were used for virtual placement of
      C1 lateral mass screws. Success was defined as avoidance of critical structures
      including the transverse foramen, vertebral groove, and spinal dura. Anatomic
      variability of the C1 vertebra and safe zones for screw placement were also
      clarified. RESULTS: Overall screw placement success for the four techniques was
      50% (Resnick), 92% (Tan et al.), 58% (Ma et al.), and 85% (Christensen et al.).
      Average posterior arch height was 6.7+/-2.1 mm, and vertebral groove height 4.9+/
      1.1 mm was the most limiting dimension to safe screw placement. A safe zone for
      screw placement was found in 100% of cases (200 screws), 17.0+/-1.1 mm from
      midline and a width of 12.6+/-1.7 mm. Posterior tubercle morphology was variable.
      CONCLUSIONS: C1 lateral mass screws could be virtually placed bilaterally in each
      of 100 clinical cases without violating critical structures. However, none of the
      previously described approaches worked in every case because of significant
      anatomic variability. The vertical starting point was particularly critical, and
      vertebral groove height was the most limiting variable. Although a reliable safe
      zone could be found in every case, preoperative planning is essential to avoid
      critical structures.

PMID- 23953730
TI  - Calcium oxalate supersaturation increases early after Roux-en-Y gastric bypass.
AB  - BACKGROUND: Calcium oxalate (CaOx) nephrolithiasis is an adverse effect of Roux
      en-Y gastric bypass surgery (RYGB). It is unknown when the increased risk for
      CaOx stone formation occurs after surgery. METHODS: We studied 13 morbidly obese
      adults undergoing RYGB with 24-hour urine collections at 4 weeks before and 1, 2,
      4, and 6 months after surgery and computed CaOx relative saturation ratio (RSR)
      by EQUIL2. RESULTS: Eleven patients were female, mean +/- standard deviation age
      was 41.1 +/- 7.2 years, and none had diabetes or chronic kidney disease. Median
      (interquartile range) urinary oxalate excretion increased linearly from 12.6
      (10.9-37.9) mg/24 hr at baseline to 28.4 (14.4-44.0) mg/24 hr at 6 months (slope
      = .188; P = .005). CaOx RSR increased significantly at 2 months after RYGB (1.4
      [1.2-2.4] to 4.9 [1.7-10.0]; P = .017) and rose throughout the study to 5.7 (3.7
      12.2) at 6 months (P = .001) with a positive linear slope (.255; P = .001). One
      patient had critical CaOx supersaturation (RSR = 34.7) and severe hyperoxaluria
      (101.7 mg/24 hr) at 6 months after RYGB. Significant decreases over time were
      seen in urine volume and sodium and potassium excretion, but no changes were
      noted in urinary pH, calcium, magnesium, or citrate. CONCLUSIONS: Our data
      suggest that CaOx RSR, and thus risk for nephrolithiasis, rises as early as 2
      months after RYGB and increases gradually in the first 6 months, largely because
      of reduced urine volume and increased urinary oxalate excretion. Interventions to
      reduce CaOx RSR, such as adequate fluid intake and agents to bind enteric
      oxalate, need to be evaluated in patients at risk for nephrolithiasis after RYGB.

PMID- 23953732
TI  - Intratumoral hemorrhage because of primary spinal mixed germ cell tumor
      presenting with atypical radiological features in an adult.
AB  - BACKGROUND CONTEXT: Germ cell tumors are known to arise in the central nervous
      system, usually in the intracranial regions. However, primary spinal mixed germ
      cell tumors are extremely rare. PURPOSE: This is the first reported case of
      intratumoral hemorrhage because of a primary spinal mixed germ cell tumor
      consisting of germinoma and immature teratoma in the conus medullaris of an adult
      patient that presented with rapid changes on magnetic resonance image (MRI). We
      report this rare case and discuss the clinical manifestations of an
      intramedullary spinal mixed germ cell tumor in adult. STUDY DESIGN: A case
      report. METHODS: A 42-year-old woman experienced buttock numbness, and a spinal
      cord tumor was observed on the conus medullaris on MRI. The patient was scheduled
      for an operation in 1 month, but she developed sudden-onset neurologic
      deterioration. Rapid progression of the tumor was observed on follow-up MRI. The
      tumor was removed by emergency surgery and was identified as a primary mixed
      germinoma and immature teratoma. RESULTS: The patient received adjuvant
      chemotherapy and radiotherapy after gross total resection. The neurologic deficit
      of the patient was relieved, and recurrence of the tumor was not observed 26
      months after the surgery. CONCLUSIONS: We present this rare case and emphasize
      the necessity of precise diagnosis and early treatment of primary spinal germ
      cell tumor. Close observation on MRI is required after surgery, and adjuvant
      chemotherapy and radiotherapy should be considered according to the pathologic
      features.

PMID- 23953733
TI  - Neurophysiological changes during shortening osteotomies of the spine.
AB  - BACKGROUND CONTEXT: Kyphotic deformities with sagittal imbalance of the spine can
      be treated with spinal osteotomies. Those procedures are known to have a high
      incidence of neurological complications, in particular at the thoracic level.
      Motor evoked potentials (MEPs) have been widely used in helping to avoid major
      neurological deficits postoperatively. Previous reports have shown that a
      significant proportion of such cases present with important transcranial MEP (Tc
      MEP) changes during surgery with some of them being predictive of postoperative
      deficits. PURPOSE: Our aim was to study Tc-MEP changes in a consecutive series of
      patients and correlate them with clinical parameters and radiological changes.
      STUDY DESIGN/SETTING: Retrospective case notes study from a prospective patient
      register. PATIENT SAMPLE: Eighteen patients undergoing posterior shortening
      osteotomies (nine at thoracic and nine at lumbar levels) for kyphosis of
      congenital, degenerative, inflammatory, or post-traumatic origin were included.
      OUTCOME MEASURES: Loss of at least 80% of Tc-MEP signal expressed as the area
      under the curve percentual change, of at least one muscle. METHODS: We studied
      the relation between outcome measure (80% Tc-MEP loss in at least one muscle
      group) and amount of posterior vertebral body shortening as well as angular
      correction measured on computed tomography scans, occurrence of postoperative
      deficits, intraoperative blood pressure at the time of the osteotomy, and
      hemoglobin (Hb) change. RESULTS: All patients showed significant Tc-MEP changes.
      In particular, greater than 80% MEP loss in at least one muscle group was
      observed in five of nine patients in the thoracic group and four of nine patients
      in the lumbar group. No surgical maneuver was undertaken as a result of this loss
      in an effort to improve motor responses other than verifying the stability of the
      construct and the extent of the decompression. Four patients developed
      postoperative deficits of radicular origin, three of them recovering fully at 3
      months. No relation was found between intraoperative blood pressure, Hb changes,
      and Tc-MEP changes. Severity of Tc-MEP loss did not correlate with postoperative
      deficits. Shortening of more than 10 mm was linked to more severe Tc-MEP changes
      in the thoracic group. CONCLUSIONS: Transcranial MEP changes during spinal
      shortening procedures are common and do not appear to predict severe
      postoperative deficits. Total loss of Tc-MEP (not witnessed in our series) might
      require a more drastic approach with possible reversal of the correction and wake
      up test.

PMID- 23953735
TI  - Finite element simulations of electrostatic dopant potentials in thin
      semiconductor specimens for electron holography.
AB  - Two-dimensional finite element simulations of electrostatic dopant potentials in
      parallel-sided semiconductor specimens that contain p-n junctions are used to
      assess the effect of the electrical state of the surface of a thin specimen on
      projected potentials measured using off-axis electron holography in the
      transmission electron microscope. For a specimen that is constrained to have an
      equipotential surface, the simulations show that the step in the projected
      potential across a p-n junction is always lower than would be predicted from the
      properties of the bulk device, but is relatively insensitive to the value of the
      surface state energy, especially for thicker specimens and higher dopant
      concentrations. The depletion width measured from the projected potential,
      however, has a complicated dependence on specimen thickness. The results of the
      simulations are of broader interest for understanding the influence of surfaces
      and interfaces on electrostatic potentials in nanoscale semiconductor devices. 

PMID- 23953736
TI  - An outbreak of measles in a prison in Yorkshire, England, December 2012-January
      2013.

PMID- 23953738
TI  - Salivary protein adsorption and Streptococccus gordonii adhesion to dental
      material surfaces.
AB  - OBJECTIVES: The initial adhesion of microorganisms to clinically used dental
      biomaterials is influenced by physico-chemical parameters like hydrophobicity and
      pre-adsorption of salivary proteins. Here, polymethyl methacrylate (PMMA),
      polyethylene (PE), polytetrafluoroethylene (PTFE), silicone (Mucopren soft),
      silorane-based (Filtek Silorane) and methacrylate-based (Tetric EvoCeram) dental
      composites, a conventional glassionomer cement as well as cobalt-chromium
      molybdenum (Co28Cr6Mo) and titanium (Ti6Al4V) were tested for adsorption of
      salivary proteins and adhesion of Streptococcus gordonii DL1. METHODS:
      Wettability of material surfaces precoated with salivary proteins or left in
      phosphate-buffered saline was determined by the measurement of water contact
      angles. Amounts of adsorbed proteins were determined directly on material
      surfaces after biotinylation of amino groups and detection by horseradish
      peroxidase-conjugated avidin-D. The same technique was used to analyze for the
      binding of biotinylated bacteria to material surfaces. RESULTS: The highest
      amount of proteins (0.18MUg/cm(2)) adsorbed to hydrophobic PTFE samples, and the
      lowest amount (0.025MUg/cm(2)) was detected on silicone. The highest number of S.
      gordonii (3.2*10(4)CFU/mm(2)) adhered to the hydrophilic glassionomer cement
      surface coated with salivary proteins, and the lowest number (4*10(3)CFU/mm(2))
      was found on the hydrophobic silorane-based composite. Hydrophobicity of pure
      material surfaces and the number of attached microorganisms were weakly
      negatively correlated. No such correlation between hydrophobicity and the number
      of bacteria was detected when surfaces were coated with salivary proteins.
      SIGNIFICANCE: Functional groups added by the adsorption of specific salivary
      proteins to material surfaces are more relevant for initial bacterial adhesion
      than hydrophobicity as a physical property.

PMID- 23953739
TI  - Cyclic fatigue testing of denture teeth for bulk fracture.
AB  - OBJECTIVES: Clinical experience with implant-supported dentures indicates that
      fracture and chipping of teeth are becoming an issue. Tooth fracture and chipping
      rates of approximately 2.5% per year are being experienced at one university.
      There has been no standardized test developed for bulk fracture or chipping of
      denture teeth. Such a test would aid in the development of improved teeth and in
      their evaluation. METHODS: Central incisor teeth were embedded in acrylic and
      loaded on incisal edges at 90 degrees  to their long axes. Teeth tested included
      ones commercially available and two sets made from improved materials designed to
      increase toughness. Cyclic loading was done at 5Hz from 20N to 135N, 150N, 175N
      and 200N. Data was analyzed using lifetime analysis software fit at each of the
      accelerated loads and then extrapolated to clinical use loads (Alta 7, Reliasoft
      Corp.) Clinical use loads were derived from extrapolation of probability of
      failure (Pf) data to 2.5% Pf. RESULTS: When carefully embedded, teeth could be
      reproducibly loaded to failure by bulk fracture involving a failure mode similar
      to that seen clinically. Clinical use loads were calculated to be in the range of
      70N. Results from accelerated loading could be fit to similar probability of
      failure distributions allowing extrapolation to clinical use loads. SIGNIFICANCE:
      This work was able to develop a clinically valid bulk fracture test for the
      fatigue failure of incisor denture teeth. It appears that teeth fabricated with
      improved materials will be expected to perform better clinically. Thus both the
      null hypotheses were rejected.

PMID- 23953737
TI  - Strategies to prevent hydrolytic degradation of the hybrid layer-A review.
AB  - OBJECTIVE: Endogenous dentin collagenolytic enzymes, matrix metalloproteinases
      (MMPs) and cysteine cathepsins, are responsible for the time-dependent hydrolysis
      of collagen matrix of hybrid layers. As collagen matrix integrity is essential
      for the preservation of long-term dentin bond strength, inhibition of endogenous
      dentin proteases is necessary for durable resin-bonded restorations. METHODS:
      Several tentative approaches to prevent enzyme function have been proposed. Some
      of them have already demonstrated clinical efficacy, while others need to be
      researched further before clinical protocols can be proposed. This review will
      examine both the principles and outcomes of techniques to prevent collagen
      hydrolysis in dentin-resin interfaces. RESULTS: Chlorhexidine, a general
      inhibitor of MMPs and cysteine cathepsins, is the most tested method. In general,
      these experiments have shown that enzyme inhibition is a promising approach to
      improve hybrid layer preservation and bond strength durability. Other enzyme
      inhibitors, e.g. enzyme-inhibiting monomers, may be considered promising
      alternatives that would allow more simple clinical application than
      chlorhexidine. Cross-linking collagen and/or dentin matrix-bound enzymes could
      render hybrid layer organic matrices resistant to degradation. Alternatively,
      complete removal of water from the hybrid layer with ethanol wet bonding or
      biomimetic remineralization should eliminate hydrolysis of both collagen and
      resin components. SIGNIFICANCE: Understanding the function of the enzymes
      responsible for the hydrolysis of hybrid layer collagen has prompted several
      innovative approaches to retain hybrid layer integrity and strong dentin bonding.
      The ultimate goal, prevention of collagen matrix degradation with clinically
      applicable techniques and commercially available materials may be achievable in
      several ways.

PMID- 23953740
TI  - Radiology-pathology conference: primary peritoneal mesothelioma.
AB  - Primary peritoneal mesothelioma is a rare neoplasm which carries a dismal
      prognosis. These highly aggressive tumors arise from mesothelial cells lining the
      peritoneum and are rapidly fatal. The neoplasm is typically associated with
      crocidolite asbestos exposure. We present the case of a 75-year-old man with
      primary peritoneal mesothelioma, with invasion into the right hepatic lobe. 

PMID- 23953741
TI  - Pre-vascularization of bone tissue-engineered constructs.
AB  - Vascularization remains one of the primary obstacles in the repair of bone
      defects. In the previous issue of Stem Cell Research &Therapy, Pedersen and
      colleagues show that co-immobilization of endothelial cells and mesenchymal stem
      cells in a tissue-engineered construct can achieve functional microvascular
      networks in vivo. These very interesting findings, together with other state-of
      the-art research in this field, are presented in this commentary. They highlight
      the vital role of mesenchymal stem cells as supporting cells to nascent blood
      vessels. The development of pre-vascularized implants by using clinically
      relevant cell sources, which could lead to rapid integration into the host
      tissue, would be of immense interest. 

PMID- 23953742
TI  - Immunohistochemical determination of estrogen receptor-alpha in canine vaginal
      biopsies throughout proestrus, estrus, and early diestrus.
AB  - The aim of this study was to describe the presence of estrogen receptor-alpha
      (ERalpha) in several vaginal histological compartments in healthy adult bitches
      throughout three estrous cycle stages (proestrus, estrus, and early diestrus) and
      to relate ERalpha presence with serum progesterone and estradiol-17beta
      concentrations. For this purpose, serial blood samples and vaginal biopsies were
      taken from five bitches every 48 hours, starting at the clinical onset of
      proestrus, marked by the beginning of serosanguineous vaginal secretion. Serum
      progesterone and estradiol-17beta concentrations were determined by RIA, whereas
      detection of steroid receptors was carried out through immunohistochemistry.
      Subjective image analysis was conducted by two independent observers in the
      following histological compartments: superficial, intermediate, and deep
      epithelia and superficial (loose) and deep (dense) stroma (connective tissue).
      Nuclear ERalpha immunoreactivity was detected in every histological compartment
      and estrous cycle stage studied. ERalpha expression varied among histological
      compartments and during stages of the cycle. Receptor expression was associated
      with estradiol-17beta and progesterone serum profiles. Most relevant cyclic
      changes were detected in the superficial and deep epithelia and in the dense
      connective tissue. The highest ERalpha expression was detected during diestrus,
      although each compartment had a different pattern throughout the other cycle
      stages. Thus, vaginal ERalpha expression in the bitch varied throughout
      proestrus, estrus, and early diestrus according to the histological compartment
      involved. 

PMID- 23953743
TI  - Role of PGF2alpha in luteolysis based on inhibition of PGF2alpha synthesis in the
      mare.
AB  - The effects of inhibition of PGF2alpha synthesis on luteolysis in mares and on
      the incidence of prolonged luteal activity were studied in controls and in a
      group treated with flunixin meglumine (FM), a PGF2alpha inhibitor (n = 6/group).
      The FM was given every 8 hours (1.0 mg/kg) on each of Days 14.0 to 16.7.
      Concentration (pg/mL) of PGF2alpha metabolite averaged over 8 hours of hourly
      blood sampling at the beginning of each day, was lower in the FM group than in
      the controls on Day 14 after ovulation (6.7 +/- 1.3 vs. 13.8 +/- 2.9, P < 0.05),
      Day 15 (15.0 +/- 3.9 vs. 35.2 +/- 10.4, P < 0.10), and Day 16 (21.9 +/- 5.7 vs.
      54.7 +/- 11.4, P < 0.03). Concentration (ng/mL) of progesterone (P4) was greater
      in the FM group than in the controls on Day 14 (10.1 +/- 0.9 vs. 7.7 +/- 0.9, P <
      0.08), Day 15 (9.2 +/- 1.0 vs. 4.3 +/- 1.0, P < 0.008), and Day 16 (5.6 +/- 1.6
      vs. 1.2 +/- 0.4, P < 0.02). The interval from ovulation to the beginning of a
      decrease in P4 and to the end of luteolysis (P4 < 1 ng/mL) was each delayed (P <
      0.03) by ~1 day in the FM group. Intervals involving the luteal phase were long
      (statistical outliers, P < 0.05) in two mares in the FM group, indicating
      prolonged luteal activity. Results supported the hypotheses that (1) inhibition
      of PGF2alpha synthesis interferes with luteolysis in mares and (2) inhibition of
      PGF2alpha at the expected time of luteolysis may lead to prolonged luteal
      activity.

PMID- 23953744
TI  - Use of quantitative 16S rRNA PCR to determine bacterial load does not augment
      conventional cerebrospinal fluid (CSF) cultures among children undergoing
      treatment for CSF shunt infection.
AB  - The aim of this study was to develop a quantitative 16S rRNA assay for
      determination of bacterial nucleic acid load in cerebrospinal fluid (CSF) shunt
      infection and to compare quantitative 16S rRNA polymerase chain reaction (PCR)
      findings to those of conventional bacterial culture in patients treated for CSF
      shunt infection. We developed a quantitative 16S rRNA PCR assay that detected
      bacterial load across a range of 2.5 * 10(9) down to 2.5 * 10(4) 16S copies/mL
      CSF under experimental conditions for numerous Gram-positive and Gram-negative
      organisms. However, when applied to archived CSF samples from 25 shunt infection
      episodes, correlations between positive bacterial culture and 16S rRNA levels
      were seen in only half of infections, and 16S rRNA levels dropped precipitously
      after an initial peak on the first day of sample collection. Bacterial load
      measured using 16S rRNA PCR does not provide sufficient information beyond
      bacterial culture to inform CSF shunt infection treatment. 

PMID- 23953745
TI  - [Hereditary neuropathy with liability to pressure palsy (HNPP): a diagnostic
      trap].
AB  - The authors report two clinical cases of a rarely observed pathology in
      orthopedic surgery daily practice: hereditary neuropathy with liability to
      pressure palsy (HNPP), which leads to dysesthesiae, hypoesthesiae and regressive
      palsies. Onset, clinical signs and electromyographic abnormalities are described.
      Forensic consequences can occur in early postoperative period. Knowledge of this
      familial pathology allows precautionary measures at surgery and avoids
      unnecessary surgical revisions. 

PMID- 23953746
TI  - Histopathological and clinical characteristics of duodenal gastrointestinal
      stromal tumors as predictors of malignancy.
AB  - BACKGROUND: Although gastrointestinal stromal tumors (GISTs) are the most common
      mesenchymal tumors of the gastrointestinal tract, they are very rare. This study
      evaluated clinical and histopathological characteristics of duodenal GISTs to
      identify factors useful in predicting prognosis for patients with these tumors.
      METHODS: A retrospective study was performed on 20 patients who had undergone
      surgery between 1987 and 2009 for duodenal GISTs. Clinical, histopathological,
      and immunohistochemical data were evaluated. Survival analyses were conducted
      using Kaplan-Meier estimates. RESULTS: In 12 patients (60%), duodenal GISTs were
      diagnosed incidentally. Eight cases (40%) were classified as high risk grade
      GISTs. Skeinoid fibers (SkF), which are eosinophilic globular hyaline deposits in
      the extracellular interstitium of the tumor, were found in 12 patients. Skeinoid
      fibers were not recognized in 8 cases, and these included 3 cases (37.5%) where
      tumors recurred after surgery and the patient died. Tumors without SkF were
      larger (81 +/- 92 vs. 23 +/- 8 mm, P < 0.001) and had a higher mitotic count
      (224.0 +/- 336.6 vs. 0.0 +/- 0.0 /50 high-power field, P < 0.001) than those with
      SkF. Survival time was shorter in patients with tumors lacking SkF (52.9 +/- 50.7
      vs. 108.9 +/- 86.5 months, P = 0.019). CONCLUSIONS: We have identified clinical
      and histopathological characteristics that were useful in predicting the
      prognosis of patients with duodenal GISTs. In this study, 60% of the tumors were
      found incidentally, SkF were not recognized in tumors from 40% of patients, and
      all cases of post-operative tumor recurrence and death occurred in this subgroup
      of patients.

PMID- 23953748
TI  - New genetic variants in the CCR5 gene and the distribution of known polymorphisms
      in Omani population.
AB  - C-C motif chemokine receptor-5 (CCR5) is a pro-inflammatory receptor that binds
      to chemokines and facilitates the entry of the R5 strain of HIV-1. A number of
      polymorphisms were identified within the promoter and coding regions of the CCR5
      gene, some of which have been found to affect the protein expression and thus
      receptor function. Although several CCR5 polymorphisms were shown to vary widely
      in their distribution among different ethnic populations, there has been no study
      addressing the potential variants of the CCR5 gene in the Omani population. The
      aim of this study was to identify the polymorphic sites that exist within the
      CCR5 gene in Omanis. Blood samples were collected from 89 Omani adult
      individuals, and genomic DNA was amplified by polymerase chain reaction and
      sequenced to identify the polymorphic sites. The distribution of the detected
      variants was examined and compared with the previously published data. Four new
      indels were detected of 32 variable positions, -2973A/-, -2894A/-, -2827TA/- and 
      2769T/-, and all were located in the 5'UTR. Furthermore, two new mutations, 
      2248G/A and +658A/G, were observed for the first time; the -2248G/A was detected
      in the intron 1 region in one subject and +658A/G in the coding region of the
      CCR5 in another subject. In silico analysis showed that the novel variations in
      the 5'UTR may have effects on the transcription factor binding sites. Therefore,
      this study demonstrates the presence of two new SNPs and four novel indels in the
      CCR5 gene in the Omani population. Our findings support the wide spectrum of
      genetic diversity reported within the CCR5 gene region among different ethnic
      groups. 

PMID- 23953747
TI  - Mirror neurons through the lens of epigenetics.
AB  - The consensus view in mirror neuron research is that mirror neurons comprise a
      uniform, stable execution-observation matching system. In this opinion article,
      we argue that, in light of recent evidence, this is at best an incomplete and
      oversimplified view of mirror neurons, where activity is actually variable and
      more plastic than previously theorized. We propose an epigenetic account for
      understanding developmental changes in sensorimotor systems, including variations
      in mirror neuron activity. Although associative and genetic accounts fail to
      consider the complexity of genetic and nongenetic interactions, we propose a new
      evolutionary developmental biology (evo-devo) perspective, which predicts that
      environmental differences early in development should produce variations in
      mirror neuron response patterns, tuning them to the social environment. 

PMID- 23953749
TI  - FOXM1 is lower in human fetal membranes after spontaneous preterm labour and
      delivery.
AB  - Spontaneous preterm birth is usually associated with infection, inflammation or
      both. Forkhead box (FOX) M1 (FOXM1), a member of the FOX family of transcription
      factors, has been associated with inflammation. The aim of this study was to
      determine whether FOXM1 regulates the expression and release of pro-labour
      mediators in human gestational tissues. FOXM1 mRNA and protein expression were
      determined in fetal membranes from women at (1) preterm no labour: Caesarean
      section with no labour and (2) preterm labour: after spontaneous labour and
      delivery. Primary amnion cells were utilised to investigate the effect of small
      interfering RNA (siRNA)-mediated gene silencing of FOXM1 on pro-labour mediators.
      Spontaneous preterm labour decreased FOXM1 gene and nuclear protein expression.
      FOXM1 silencing in primary amnion cells increased interleukin (IL)-1beta-induced
      pro-inflammatory cytokines (IL-6 and IL-8 mRNA expression and secretion),
      cyclooxygenase (COX)-2 expression and subsequent prostaglandin (PG)E2 and
      PGF2alpha release as well as gene expression and secretion of the matrix
      degrading enzyme matrix metalloproteinase 9 (MMP-9). In conclusion, spontaneous
      preterm labour is associated with decreased FOXM1 expression in fetal membranes. 

PMID- 23953750
TI  - Family presence during resuscitation (FPDR): Perceived benefits, barriers and
      enablers to implementation and practice.
AB  - INTRODUCTION: There are a number of perceived benefits and barriers to family
      presence during resuscitation (FPDR) in the emergency department, and debate
      continues among health professionals regarding the practice of family presence.
      AIM: This review of the literature aims to develop an understanding of the
      perceived benefits, barriers and enablers to implementing and practicing FPDR in
      the emergency department. RESULTS: The perceived benefits include; helping with
      the grieving process; everything possible was done, facilitates closure and
      healing and provides guidance and family understanding and allows relatives to
      recognise efforts. The perceived barriers included; increased stress and anxiety,
      distracted by relatives, fear of litigation, traumatic experience and family
      interference. There were four sub themes that emerged from the literature around
      the enablers of FPDR, these included; the need for a designated support person,
      the importance of training and education for staff and the development of a
      formal policy within the emergency department to inform practice. CONCLUSION: In
      order to ensure that practice of FPDR becomes consistent, emergency personnel
      need to understand the need for advanced FPDR training and education, the
      importance of a designated support person role and the evidence of FPDR policy as
      enablers to implementation.

PMID- 23953751
TI  - Evaluation of potential PET imaging probes for the orexin 2 receptors.
AB  - A wide range of central nervous system (CNS) disorders, particularly those
      related to sleep, are associated with the abnormal function of orexin (OX)
      receptors. Several orexin receptor antagonists have been reported in recent
      years, but currently there are no imaging tools to probe the density and function
      of orexin receptors in vivo. To date there are no published data on the
      pharmacokinetics (PK) and accumulation of some lead orexin receptor antagonists.
      Evaluation of CNS pharmacokinetics in the pursuit of positron emission tomography
      (PET) radiotracer development could be used to elucidate the association of
      orexin receptors with diseases and to facilitate the drug discovery and
      development. To this end, we designed and evaluated carbon-11 labeled compounds
      based on diazepane orexin receptor antagonists previously described. One of the
      synthesized compounds, [(11)C]CW4, showed high brain uptake in rats and further
      evaluated in non-human primate (NHP) using PET-MR imaging. PET scans performed in
      a baboon showed appropriate early brain uptake for consideration as a
      radiotracer. However, [(11)C]CW4 exhibited fast kinetics and high nonspecific
      binding, as determined after co-administration of [(11)C]CW4 and unlabeled CW4.
      These properties indicate that [(11)C]CW4 has excellent brain penetrance and
      could be used as a lead compound for developing new CNS-penetrant PET imaging
      probes of orexin receptors. 

PMID- 23953752
TI  - Role of minor salivary glands in developing patient-rated xerostomia and sticky
      saliva during day and night.
AB  - PURPOSE: The purpose of this prospective study was to investigate the
      relationship between xerostomia during the day (XERday) and night (XERnight) and
      sticky saliva during the day (STICday) and night (STICnight) and dose
      distributions in different major and minor salivary glands among head and neck
      cancer (HNC) patients treated with primary radiotherapy (RT) or chemoradiation
      (CHRT). METHODS AND MATERIALS: The study population was composed of 201
      consecutive HNC patients treated with intensity modulated radiotherapy (IMRT) or
      3-dimensional conformal radiotherapy (3D-CRT). All patients were included in a
      standard follow up programme in which acute and late side effects and quality of
      life (QoL) were prospectively assessed, prior to, during and after treatment. The
      primary endpoints were XERday, XERnight, STICday, STICnight as assessed by the
      Groningen Radiotherapy Induced Xerostomia questionnaire (GRIX) six months after
      completion of treatment. Organs at risk (OARs) potentially involved in salivary
      function were delineated on planning-CT, including the parotid, submandibular and
      sublingual glands and the minor glands in the soft palate, buccal mucosa and
      lips. Patients with moderate-to-severe xerostomia or moderate-to-severe sticky
      saliva, respectively, at baseline were excluded. In order to determine which
      salivary glands were most important, a multivariate logistic regression analysis
      with an extended bootstrapping technique was used. RESULTS: In total, 29% and 19%
      of the cases suffered from XERday and XERnight, respectively. The multivariate
      analysis showed that baseline xerostomia and the mean parotid gland dose were the
      most important predictors for XERday and XERnight. At 6months after (CH)RT, 10%
      and 12% of the cases reported STICday and STICnight respectively. We were not
      able to identify prognostic factors related to dose distributions with regard to
      STICday. The mean submandibular gland dose was associated with STICnight.
      Baseline xerostomia and sticky saliva scores on the GRIX were associated with
      XERday, XERnight, STICday. Increasing age was correlated with both XERnight and
      STICnight. CONCLUSION: Organs at risk for XERday and STICday are similar to
      organs at risk for XERnight and STICnight.

PMID- 23953753
TI  - Impact of comorbidity on treatment outcome in head and neck squamous cell
      carcinoma - a systematic review.
AB  - The significant association with tobacco and alcohol combined with advanced age
      at time of diagnosis predispose head and neck squamous cell carcinoma (HNSCC)
      patients to increased risk of comorbidities. The presence of comorbidity affects
      treatment, treatment selection and subsequent outcome. Multiple studies have
      demonstrated comorbidity to be a strong prognostic factor for survival, and
      therefore comorbidity can be a major confounder in clinical trials. This review
      provides a summary of the current literature on comorbidity in head and neck
      cancer, measurements of comorbidity, the impact of comorbidity on treatment,
      treatment selection, and survival. A systematic search was performed in six
      electronic databases. In all, 31 papers were selected for this review. A meta
      analysis on the prognostic impact of comorbidity was performed including 10
      studies. Furthermore, 21 studies concerning comorbidity were reviewed. Several
      valid indices to classify comorbidity were described in the literature, none
      proven to be superior over the other. The prevalence of comorbidity increased
      with age and the presence of comorbidity influenced treatment and treatment
      selection. Furthermore, comorbidity was associated with lower socio economic
      status and increased the risk of early retirement after treatment. The meta
      analysis on comorbidity as a prognostic factor, including 22,932 patients, showed
      that overall survival was significantly worsened among patients with comorbidity
      (HR=1.38 (1.32-1.43)). Increasing comorbidity-score was associated with increased
      risk of death. Comorbidity is important in HNSCC and significantly impacts on
      overall survival. Trials concerning HNSCC should always include information on
      comorbidity and randomized trials should stratify patients according to
      comorbidity in order to avoid bias in the study. 

PMID- 23953754
TI  - The effect of odor valence on olfactory performance in schizophrenia patients,
      unaffected relatives and at-risk youth.
AB  - Given the presence of odor identification impairment in individuals with
      schizophrenia and recent evidence of aberrant odor hedonic processing, the aim of
      this investigation was to examine the influence of valence and intensity on odor
      identification in schizophrenia patients, their first-degree family members, and
      young persons at clinical risk for psychosis. Participants completed the 16-item
      Sniffin' Stick Odor Identification Test. A logistic regression was conducted to
      assess the influence of valence and intensity on odor identification accuracy.
      Identification performance in the schizophrenia patients and youths at clinical
      risk for psychosis was significantly influenced by odor valence, but not
      intensity. Identification accuracy in first-degree family members was not
      influenced by valence or intensity. These data suggest that abnormalities in odor
      valence perception may represent an environmentally-mediated marker for hedonic
      disturbance that could have predictive utility in future conversion to psychosis.
      Further research examining the utility of odor valence measures as markers for
      psychosis risk is warranted. 

PMID- 23953755
TI  - Schizophrenia and the risk of cardiovascular diseases: a meta-analysis of
      thirteen cohort studies.
AB  - BACKGROUND: Numerous studies have investigated the relationship between
      schizophrenia and the incidence of cardiovascular disease (CVD), but their
      results were not entirely consistent. Our study aimed to elucidate the
      association between schizophrenia and the risk of CVD by a meta-analysis of
      cohort studies. METHODS: PubMed, the Cochrane Library, and EMBASE databases were
      searched to identify relevant studies that met the prespecified inclusion
      criteria. We also reviewed reference lists from the retrieved articles. Relative
      risks (RRs) and 95% confidence intervals (CIs) were extracted and pooled using
      the fixed-effect or random-effects models. RESULTS: Thirteen studies involving
      3,549,950 participants, with outcomes of CVD reported for 422,698, were included
      in the meta-analysis. The follow-up period ranged from 1.6 to 36.0 years. The
      meta-analysis found that the pooled RRs for schizophrenia compared with the
      reference group were 1.53 (95% CI: 1.27-1.86) for the incidence of CVD, 1.20 (95%
      CI: 0.93-1.53) for coronary heart disease (CHD), 1.71 (95% CI: 1.19-2.46) for
      stroke, and 1.81 (95% CI: 1.42-2.29) for congestive heart failure (CHF).
      Sensitivity analysis after the exclusion of a single cohort or using the
      unadjusted RRs yielded similar results to the primary overall estimations. No
      evidence of publication bias was observed. CONCLUSIONS: Schizophrenia is
      associated with increased incidence of CVD, stroke and CHF, and might also
      increase the risk of CHD. Greater attention should be paid to schizophrenia
      patients to prevent the occurrence of CVD and to decrease the risk of cardiac
      morbidity.

PMID- 23953757
TI  - NSE level in combined neuroendocrine and adenocarcinoma EGFR mutated lung cancer
      resistant to EGFR-TKI.

PMID- 23953756
TI  - Relationships between health literacy and heart failure knowledge, self-efficacy,
      and self-care adherence.
AB  - BACKGROUND: It has been argued that only 12% of adults have the necessary health
      literacy to manage their health care effectively, which can lead to difficulties
      in self-care activities, such as medication adherence. Prior research suggests
      that health literacy may influence knowledge, self-efficacy and self-care, but
      this has not been fully examined. OBJECTIVE: To test a model to explain the
      relationships between health literacy, heart failure knowledge, self-efficacy,
      and self-care. METHODS: Prior to receiving clinic-based education, newly referred
      patients to 3 heart failure clinics completed assessments of health literacy,
      heart failure knowledge, self-efficacy, self-care, and demographics. Structural
      equation modeling was completed to examine the strength of the inter-variable
      relationships. RESULTS: Of 81 participants recruited, data from 63 patients were
      complete. Health literacy was independently associated with knowledge (P <
      0.001). Health literacy was not related to self-care. Self-efficacy was
      independently-associated with self-care adherence (P = 0.016). No other
      relationships were statistically significant. The model had good fit (comparative
      fit index = 1.000) and explained 33.6% of the variance in knowledge and 27.6% in
      self-care. CONCLUSIONS: Health literacy influences knowledge about heart failure
      but not self-care adherence. Instead, self-efficacy influenced self-care
      adherence. Future research should incorporate additional factors that may better
      model the relationships between health literacy, knowledge, self-efficacy, and
      self-care.

PMID- 23953758
TI  - Radiochemotherapy as the standard treatment for both elderly and non-elderly fit
      patients with locally advanced (stage III) nonsmall cell lung cancer.

PMID- 23953759
TI  - Homeostatic and injury-induced microglia behavior in the aging brain.
AB  - Microglia cells are essential for brain homeostasis and have essential roles in
      neurodegenerative diseases. Aging is the main risk factor for most
      neurodegenerative diseases, and age-related changes in microglia may contribute
      to the susceptibility of the aging brain to dysfunction and neurodegeneration. We
      have analyzed morphology and dynamic behavior of neocortical microglia in their
      physiological environment in young adult (3-month-old), adult (11- to 12-month
      old), and aged (26- to 27-month-old) C57BL/6J-Iba1-eGFP mice using in vivo 2
      photon microscopy. Results show that surveying microglial cells in the neocortex
      exhibit age-related soma volume increase, shortening of processes, and loss of
      homogeneous tissue distribution. Furthermore, microglial process speed
      significantly decreased with age. While only a small population of microglia
      showed soma movement in adult mice, the microglia population with soma movement
      was increased in aged mice. However, in response to tissue injury, the dynamic
      microglial response was age-dependently diminished. These results provide novel
      insights into microglial behavior and indicate that microglial dysfunction in the
      aging brain may contribute to age-related cognitive decline and neurodegenerative
      diseases. 

PMID- 23953760
TI  - Molecular diagnosis of canine visceral leishmaniasis: a comparative study of
      three methods using skin and spleen from dogs with natural Leishmania infantum
      infection.
AB  - Polymerase chain reaction (PCR) and its variations represent highly sensitive and
      specific methods for Leishmania DNA detection and subsequent canine visceral
      leishmaniasis (CVL) diagnosis. The aim of this work was to compare three
      different molecular diagnosis techniques (conventional PCR [cPCR], seminested PCR
      [snPCR], and quantitative PCR [qPCR]) in samples of skin and spleen from 60
      seropositive dogs by immunofluorescence antibody test and enzyme-linked
      immunosorbent assay. Parasitological analysis was conducted by culture of bone
      marrow aspirate and optical microscopic assessment of ear skin and spleen samples
      stained with Giemsa, the standard tests for CVL diagnosis. The primers L150/L152
      and LINR4/LIN17/LIN19 were used to amplify the conserved region of the Leishmania
      kDNA minicircle in the cPCR, and snPCR and qPCR were performed using the DNA
      polymerase gene (DNA pol alpha) primers from Leishmania infantum. The
      parasitological analysis revealed parasites in 61.7% of the samples.
      Sensitivities were 89.2%, 86.5%, and 97.3% in the skin and 81.1%, 94.6%, and
      100.0% in spleen samples used for cPCR, snPCR, and qPCR, respectively. We
      demonstrated that the qPCR method was the best technique to detect L. infantum in
      both skin and spleen samples. However, we recommend the use of skin due to the
      high sensitivity and sampling being less invasive.

PMID- 23953761
TI  - The molecular prevalence and MSA-2b gene-based genetic diversity of Babesia bovis
      in dairy cattle in Thailand.
AB  - Bovine babesiosis is an economically significant disease that affects dairy
      farming operations in Thailand. In the present study, 1824 blood-DNA samples
      prepared from cattle bred in 4 different regions of the country (North,
      Northeast, Central, and South) were screened using a nested PCR for the specific
      detection of Babesia bovis. While the overall prevalence of B. bovis was 8.8%,
      the Central region of Thailand was found to be a high-risk area of the country,
      as the prevalence of the parasite was 15.0%. The positive rate was relatively
      higher among the animals of 1-5 years of age. The genetic diversity among the B.
      bovis parasites was also studied based on their MSA-2b gene, and the findings
      showed that the Thai sequences were dispersed across 8 of 13 total clades
      observed in the phylogram. Three of these clades were formed only of Thai
      sequences. Similarity among the deduced MSA-2b amino acid sequences determined in
      the present study was 68.3-100%. In conclusion, the present study found that all
      the locations surveyed were infected with B. bovis and that the parasite
      populations in Thailand were genetically diverse. Our findings highlight the need
      for further studies in Thailand to generate more information before a sound
      control strategy could be implemented against B. bovis.

PMID- 23953762
TI  - Effects of training and weight support on muscle activation in Parkinson's
      disease.
AB  - The aim of this study was to investigate the effect of high-intensity locomotor
      training on knee extensor and flexor muscle activation and adaptability to
      increased body-weight (BW) support during walking in patients with Parkinson's
      disease (PD). Thirteen male patients with idiopathic PD and eight healthy
      participants were included. The PD patients completed an 8-week training program
      on a lower-body, positive-pressure treadmill. Knee extensor and flexor muscles
      activation during steady treadmill walking (3 km/h) were measured before, at the
      mid-point, and after training. Increasing BW support decreased knee extensor
      muscle activation (normalization) and increased knee flexor muscle activation
      (abnormal) in PD patients when compared to healthy participants. Training
      improved flexor peak muscle activation adaptability to increased (BW) support
      during walking in PD patients. During walking without BW support shorter knee
      extensor muscle off-activation time and increased relative peak muscle activation
      was observed in PD patients and did not improve with 8 weeks of training. In
      conclusion, patients with PD walked with excessive activation of the knee
      extensor and flexor muscles when compared to healthy participants. Specialized
      locomotor training may facilitate adaptive processes related to motor control of
      walking in PD patients.

PMID- 23953763
TI  - Muscle activation and coactivation during five-time-sit-to-stand movement in
      patients undergoing total knee arthroplasty.
AB  - Quadriceps weakness is prevalent with knee osteoarthritis (OA) and after total
      knee arthroplasty (TKA). To compensate for quadriceps dysfunction, patients often
      alter movement strategies. Little is known about muscle coordination during sit
      to-stand (concentric) and stand-to-sit (eccentric) movements in the acute
      postoperative period. This investigation characterized the distribution of muscle
      activation between the concentric and eccentric phases during a five-time-sit-to
      stand (FTSTS) movement in late stage OA and one month after TKA. Patients and
      healthy participants performed a FTSTS while recording bilateral ground reaction
      forces (GRFs) and electromyography (EMG). Concentric and eccentric ensemble
      averages of the GRF and EMG were calculated for the concentric and eccentric
      phases. Coactivation indices, integrated EMG, and GRF were calculated for each
      limb and phase. Patients demonstrated higher eccentric coactivation than the
      healthy group. Postoperative loading was higher in the nonsurgical limb.
      Postoperative quadriceps activity was lower in the concentric phase and higher in
      the eccentric phase than the healthy group. Higher coactivation in the patients
      resulted from sustained distribution of quadriceps activity throughout the
      eccentric phase. This indicated an inability to coordinate muscle firing when
      rapidly lowering to a chair and occurred despite unloading of the surgical limb.
      Although these patterns may serve as a protective strategy, they may also impede
      recovery of muscle function after TKA. 

PMID- 23953764
TI  - Is the MMR vaccination programme failing to protect women against rubella
      infection?
AB  - In recent years the number of pregnant women susceptible to rubella has increased
      markedly. In the West Midlands the proportion has risen from 1.4% in 2004 to 6.9%
      in 2011. Locally, the proportion of non-immune women ranges from 1.6% in those
      born prior to 1976 to 17.8% in those born since 1986. The latter group comprises
      those given MMR in their second year with no further booster doses. The number of
      non-immune women will continue to rise as a consequence of low MMR uptake in the
      late 1990s. Repeat testing of samples with values <10 IU/ml and the need to
      vaccinate women postnatally have increased the workload of laboratory and
      maternity units. Screening for rubella in pregnancy has no advantages for the
      current pregnancy and it may be time to review the universal MMR vaccination
      programme which in turn would remove the need for continuing this practice.

PMID- 23953765
TI  - What does universal health coverage mean?

PMID- 23953766
TI  - Percutaneous vesicoamniotic shunting versus conservative management for fetal
      lower urinary tract obstruction (PLUTO): a randomised trial.
AB  - BACKGROUND: Fetal lower urinary tract obstruction (LUTO) is associated with high
      perinatal and long-term childhood mortality and morbidity. We aimed to assess the
      effectiveness of vesicoamniotic shunting for treatment of LUTO. METHODS: In a
      randomised trial in the UK, Ireland, and the Netherlands, women whose pregnancies
      with a male fetus were complicated by isolated LUTO were randomly assigned by a
      central telephone and web-based randomisation service to receive either the
      intervention (placement of vesicoamniotic shunt) or conservative management.
      Allocation could not be masked from clinicians or participants because of the
      invasive nature of the intervention. Diagnosis was by prenatal ultrasound. The
      primary outcome was survival of the baby to 28 days postnatally. All primary
      analyses were done on an intention-to-treat basis, but these results were
      compared with those of an as-treated analysis to investigate the effect of a
      fairly large proportion of crossovers. We used Bayesian methods to estimate the
      posterior probability distribution of the effectiveness of vesicoamniotic
      shunting at 28 days. The study is registered with the ISRCTN Register, number
      ISRCTN53328556. FINDINGS: 31 women with singleton pregnancies complicated by LUTO
      were included in the trial and main analysis, with 16 allocated to the
      vesicoamniotic shunt group and 15 to the conservative management group. The study
      closed early because of poor recruitment. There were 12 livebirths in each group.
      In the vesicoamniotic shunt group one intrauterine death occurred and three
      pregnancies were terminated. In the conservative management group one
      intrauterine death occurred and two pregnancies were terminated. Of the 16
      pregnancies randomly assigned to vesicoamniotic shunting, eight neonates survived
      to 28 days, compared with four from the 15 pregnancies assigned to conservative
      management (intention-to-treat relative risk [RR] 1.88, 95% CI 0.71-4.96;
      p=0.27). Analysis based on treatment received showed a larger effect (3.20, 1.06
      9.62; p=0.03). All 12 deaths were caused by pulmonary hypoplasia in the early
      neonatal period. Sensitivity analysis in which non-treatment-related terminations
      of pregnancy were excluded made some slight changes to point estimates only.
      Bayesian analysis in which the trial data were combined with elicited priors from
      experts suggested an 86% probability that vesicoamniotic shunting increased
      survival at 28 days and a 25% probability that it had a large, clinically
      important effect (defined as a relative increase of 55% or more in the proportion
      of neonates who survived). There was substantial short-term and long-term
      morbidity in both groups, including poor renal function-only two babies (both in
      the shunt group) survived to 2 years with normal renal function. Seven
      complications occurred in six fetuses from the shunt group, including spontaneous
      ruptured membranes, shunt blockage, and dislodgement. These complications
      resulted in four pregnancy losses. INTERPRETATION: Survival seemed to be higher
      in the fetuses receiving vesicoamniotic shunting, but the size and direction of
      the effect remained uncertain, such that benefit could not be conclusively
      proven. Our results suggest that the chance of newborn babies surviving with
      normal renal function is very low irrespective of whether or not vesicoamniotic
      shunting is done. FUNDING: UK National Institute of Health Research, Wellbeing of
      Women, Hannah Eliza Guy Charity (Birmingham Children's Hospital Charity).

PMID- 23953767
TI  - Malaria.
AB  - Although global morbidity and mortality have decreased substantially, malaria, a
      parasite infection of red blood cells, still kills roughly 2000 people per day,
      most of whom are children in Africa. Two factors largely account for these
      decreases; increased deployment of insecticide-treated bednets and increased
      availability of highly effective artemisinin combination treatments. In large
      trials, parenteral artesunate (an artemisinin derivative) reduced severe malaria
      mortality by 22.5% in Africa and 34.7% in Asia compared with quinine, whereas
      adjunctive interventions have been uniformly unsuccessful. Rapid tests have been
      an important addition to microscopy for malaria diagnosis. Chemopreventive
      strategies have been increasingly deployed in Africa, notably intermittent
      sulfadoxine-pyrimethamine treatment in pregnancy, and monthly amodiaquine
      sulfadoxine-pyrimethamine during the rainy season months in children aged between
      3 months and 5 years across the sub-Sahel. Enthusiasm for malaria elimination has
      resurfaced. This ambitious but laudable goal faces many challenges, including the
      worldwide economic downturn, difficulties in elimination of vivax malaria,
      development of pyrethroid resistance in some anopheline mosquitoes, and the
      emergence of artemisinin resistance in Plasmodium falciparum in southeast Asia.
      We review the epidemiology, clinical features, pathology, prevention, and
      treatment of malaria. 

PMID- 23953768
TI  - A road safety performance indicator for vehicle fleet compatibility.
AB  - This paper discusses the development and the application of a safety performance
      indicator which measures the intrinsic safety of a country's vehicle fleet
      related to fleet composition. The indicator takes into account both the 'relative
      severity' of individual collisions between different vehicle types, and the share
      of those vehicle types within a country's fleet. The relative severity is a
      measure for the personal damage that can be expected from a collision between two
      vehicles of any type, relative to that of a collision between passenger cars. It
      is shown how this number can be calculated using vehicle mass only. A sensitivity
      analysis is performed to study the dependence of the indicator on parameter
      values and basic assumptions made. The indicator is easy to apply and satisfies
      the requirements for appropriate safety performance indicators. It was developed
      in such a way that it specifically scores the intrinsic safety of a fleet due to
      its composition, without being influenced by other factors, like helmet wearing.
      For the sake of simplicity, and since the required data is available throughout
      Europe, the indicator was applied to the relative share of three of the main
      vehicle types: passenger cars, heavy goods vehicles and motorcycles. Using the
      vehicle fleet data from 13EU Member States and Norway, the indicator was used to
      rank the countries' safety performance. The UK was found to perform best in terms
      of its fleet composition (value is 1.07), while Greece has the worst performance
      with the highest indicator value (1.41). 

PMID- 23953769
TI  - Gynecologic oncology quality measures: what really matters?

PMID- 23953770
TI  - Changes in border movement of the mandible in skeletal Class III before and after
      orthognathic surgery.
AB  - The purpose of this study was to examine the changes in border movement of the
      mandible before and after mandibular ramus osteotomy in patients with
      prognathism. The subjects were 73 patients with mandibular prognathism who
      underwent sagittal split ramus osteotomy (SSRO) with and without Le Fort I
      osteotomy. Border movement of the mandible was recorded with a mandibular
      movement measure system (K7) preoperatively and at 6 months postoperatively. Of
      the 73 patients, 21 had measurements taken at 1.5 years postoperative. Data were
      compared between the pre- and postoperative states, and the differences analyzed
      statistically. There was no significant difference between SSRO alone and SSRO
      with Le Fort I osteotomy in the time-course change. The values at 6 months
      postoperative were significantly lower than the preoperative values for maximum
      vertical opening (P=0.0066), maximum antero-posterior movement from the centric
      occlusion (P=0.0425), and centric occlusion to maximum opening (P=0.0300).
      However, there were no significant differences between the preoperative and 1.5
      years postoperative measurements. This study suggests that a postoperative
      temporary reduction in the border movement of the mandible could recover by 1.5
      years postoperative, and the additional procedure of a Le Fort I osteotomy does
      not affect the recovery of mandibular motion after SSRO. 

PMID- 23953771
TI  - Aesthetic and functional implications following rotation of the maxillomandibular
      complex in orthognathic surgery: a systematic review.
AB  - The manipulation of the maxillomandibular complex (MMC) in orthognathic surgery
      has been used widely in the treatment of dentofacial deformities so as to
      optimize aesthetic and functional results, making these more stable in the long
      term. The aim of the present study was to perform a systematic literature review
      of the aesthetic and functional implications following rotation of the occlusal
      plane in orthognathic surgery, by evaluating skeletal stability, facial harmony,
      respiratory function, and temporomandibular joint (TMJ) function after clockwise
      or counterclockwise rotation of the MMC. A survey of Scopus, PubMed, and Cochrane
      databases was performed through which 10 papers were selected for the final
      review. From this review, it could be concluded that facial aesthetics, TMJ
      function, and skeletal and occlusal stability in the orthosurgical treatment of
      dentofacial deformities may be influenced by the surgical manipulation of the MMC
      (clockwise or counterclockwise rotation). However, although this treatment
      technique is used widely today, the results of the present study do not provide
      sufficient scientific evidence with regard to the choice of this approach. 

PMID- 23953773
TI  - The PLUTO trial: a missed opportunity.

PMID- 23953772
TI  - Human pluripotent stem cell-derived cardiomyocytes for heart regeneration, drug
      discovery and disease modeling: from the genetic, epigenetic, and tissue modeling
      perspectives.
AB  - Heart diseases remain a major cause of mortality and morbidity worldwide.
      However, terminally differentiated human adult cardiomyocytes (CMs) possess a
      very limited innate ability to regenerate. Directed differentiation of human
      embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) into CMs
      has enabled clinicians and researchers to pursue the novel therapeutic paradigm
      of cell-based cardiac regeneration. In addition to tissue engineering and
      transplantation studies, the need for functional CMs has also prompted
      researchers to explore molecular pathways and develop strategies to improve the
      quality, purity and quantity of hESC-derived and iPSC-derived CMs. In this
      review, we describe various approaches in directed CM differentiation and driven
      maturation, and discuss potential limitations associated with hESCs and iPSCs,
      with an emphasis on the role of epigenetic regulation and chromatin remodeling,
      in the context of the potential and challenges of using hESC-CMs and iPSC-CMs for
      drug discovery and toxicity screening, disease modeling, and clinical
      applications. 

PMID- 23953774
TI  - Good neurologic recovery after cardiac arrest using hypothermia through
      continuous renal replacement therapy.
AB  - Therapeutic hypothermia (TH) is becoming a standard of care to mitigate
      neurologic injury in cardiac arrest survivors. Several cooling methods are
      available for use in TH. For maintaining a target temperature, intravascular
      cooling is superior to, more efficacious than, and safer than surface cooling
      methods. The use of an intravenous cooling catheter is independently associated
      with a higher odds ratio for survival. However, many techniques use commercially
      developed equipment that is expensive to purchase and use. The application and
      popularization of the intravascular cooling method have been difficult. In
      patients with pulmonary edema or cardiac insufficiency, liquid is restricted, so
      intravascular cooling systems cannot be used. Studies have shown abnormalities
      mimicking the immunologic and coagulation disorders observed in severe sepsis.
      Continuous renal replacement therapy has been widely used in the intensive care
      unit to improve clinical parameters and survival in patients with multiple-organ
      dysfunction of septic origin. Continuous renal replacement therapy can also be
      used as another type of core cooling method. We used continuous renal replacement
      therapy as a cooling method to induce TH in a patient who had a cardiac arrest,
      and the patient regained consciousness 52 hours later.

PMID- 23953775
TI  - Relationship between sleep disorders and other non-motor symptoms in Parkinson's
      disease.
AB  - BACKGROUND: The association between sleep disorders and other non-motor symptoms
      (NMS) in Parkinson's disease (PD) has been scarcely investigated. OBJECTIVE: To
      describe the prevalence of insomnia and hypersomnia in PD and analyze their
      relationship with other NMS. METHODS: Cross-sectional, multicenter study
      including 388 PD patients evaluated with Hoehn and Yahr, Clinical Impression of
      Severity Index for PD, Scales for Outcomes in Parkinson's Disease (SCOPA)
      Sleep(S), SCOPA-Cognition, SCOPA-Psychiatric Complications, SCOPA-Autonomic,
      Hospital Anxiety and Depression Scale, and fatigue and pain visual analogue
      scales. Spearman correlation coefficients, Mann-Whitney test and multiple linear
      regression analysis were applied. RESULTS: Mean age (54% male) was 65.9 +/- 11.2
      years old, with disease duration of 8.1 +/- 6.0 years and median HY = 2 (range: 1
      5). Mean SCOPA-S nocturnal sleep (NS) was 5.4 +/- 4.0 (range: 0-15), daytime
      sleepiness (DS) was 3.76 +/- 3.04 (range: 0-15). Most of the sample declared
      nocturnal or daytime sleep problems (87.4%). Weak-to-moderate correlations were
      found between sleep disturbances and other NMS (range: 0.14-0.37). SCOPA-S
      subscales showed higher scores with the presence of most other NMS such as
      psychiatric complications and autonomic dysfunctions (p < 0.05). Regression
      models showed that fatigue, depression, urinary, cardiovascular, and
      thermoregulatory dysfunctions were significant determinants of SCOPA-NS score
      (variance: 23%); cognitive impairment, urinary, cardiovascular, and pupillomotor
      disorders influenced SCOPA-DS score (variance: 14%). CONCLUSIONS: Insomnia and
      daytime sleepiness are extremely prevalent in PD. Depression, fatigue, cognitive
      impairment, cardiovascular, urinary and thermoregulatory dysfunctions may
      contribute to insomnia/hypersomnia. This is the first clinical study to relate
      cardiovascular and thermoregulatory dysfunctions with sleep in PD.

PMID- 23953776
TI  - Molecular mechanisms of HPV induced carcinogenesis in head and neck.
AB  - A growing subgroup of oropharyngeal cancers is initiated by infection with high
      risk human papillomaviruses (HPVs). In parallel to mounting epidemiological
      evidence, solid experimental data support a causal association between HPV and a
      subset of oropharyngeal cancers. This Review summarizes the main events of the
      HPV life cycle, the functions of the viral oncoproteins, and the implications of
      HPV infection on their hosts, with an emphasis on carcinogenic mechanisms in
      oropharyngeal cancer. The demonstration that HPVs have a role in head and neck
      carcinogenesis has fuelled the expectation that HPV-targeted therapeutic
      strategies may prove curative in these cancers. 

PMID- 23953777
TI  - An exploratory study of the informational and psychosocial needs of patients with
      human papillomavirus-associated oropharyngeal cancer.
AB  - OBJECTIVES: Although the incidence of oropharyngeal squamous cell carcinoma
      (OPSCC) attributable to human papillomavirus (HPV) is rapidly increasing,
      patients' informational and psychosocial needs related to the sexual transmission
      of HPV remain unexplored. The goal of this exploratory study was to assess
      informational and psychosocial needs of HPV+ OPSCC patients and identify
      psychosocial challenges associated with having an HPV+ cancer. METHODS: Patients
      (N=62; 87% male; mean age=56years) with HPV+ OPSCC and in cohabitating
      relationships completed paper-pencil questionnaires assessing their HPV-related
      knowledge (e.g., cancer etiology), information needs (e.g., communicability),
      psychosocial concerns (e.g., relational consequences, self-blame) and measures of
      distress and health behaviors. Medical information was obtained from patients'
      electronic medical records. RESULTS: Sixty-six percent of patients correctly
      identified their HPV status but only 35% of them recognized HPV as their putative
      cancer cause. The majority of patients disclosed their HPV status to their
      partner, 41% discussed transmission of the virus, and only 23% felt informed
      regarding potential transmission risks and precautions. Thirty-nine percent want
      their oncologist to discuss more about HPV-related issues and 58% sought this
      from other sources. Over one-third said they would be interested in more HPV
      related information. Patients reported moderate levels of distress (mean=3.52,
      SD=2.54, possible range 0-10) and relatively low levels of self-blame (mean=2.27,
      SD=1.23, possible range 1-4) with distress and self-blame being significantly
      correlated (r=.38, p=.005). CONCLUSION: Significant knowledge gaps exist
      regarding patients' understanding of the link between HPV and OPSCC and the
      implications of infectious etiology. Future research is encouraged to establish
      best practice guidelines.

PMID- 23953778
TI  - Lack of claudin-7 is a strong predictor of regional recurrence in oral and
      oropharyngeal squamous cell carcinoma.
AB  - OBJECTIVES: Adequate treatment of oral and oropharyngeal squamous cell carcinoma
      (OSCC) is dependent on correctly predicting the presence of lymph node
      metastases. Current methods to diagnose nodal metastases partly result in
      overtreatment with associated morbidity and undertreatment with decreased disease
      free survival. E-cadherin has been studied extensively as potential marker for
      lymph node metastases. EpCAM and claudin-7 have a functional relationship with E
      cadherin, forming a complex that promotes tumourigenicity in vitro. We
      hypothesize that the co-expression patterns of these related molecules is a
      better prognostic marker for nodal status and regional recurrences. MATERIALS AND
      METHODS: We constructed separate tissue microarrays of tumour centre and tumour
      invasive front of 227 OSCC with complete clinicopathological and follow-up data,
      including HPV status, and performed immunohistochemistry for these molecules.
      RESULTS: Lack of E-cadherin and presence of cytoplasmic EpCAM expression in the
      tumour front were predictive for nodal metastasis, but no co-expression pattern
      was found clinically relevant. Lack of claudin-7 in the tumour centre was highly
      and independently predictive for shorter regional disease-free survival (HR=0.19;
      95%CI: 0.06-0.62) and disease-specific survival (HR=0.43; 95%CI: 0.21-0.87). High
      risk HPV was not associated with any marker. CONCLUSIONS: The expression of E
      cadherin and EpCAM, depending on the specific tumour sublocalization, is
      predictive for nodal status. However, co-expression did not improve the
      prediction of nodal status, indicating that the proposed in vitro complex is not
      functional in clinical samples. Additionally, lack of claudin-7 expression in the
      tumour centre may be used to identify patients with increased risk for regional
      recurrence.

PMID- 23953779
TI  - The management of the older adult patient with anomalous left coronary artery
      from the pulmonary artery syndrome: a presentation of two cases and review of the
      literature.
AB  - ALCAPA (anomalous left coronary artery from pulmonary artery) syndrome is a rare
      congenital abnormality that involves an anomalous insertion of the left coronary
      artery into the pulmonary artery. Ninety percent of patients present in the first
      year of life with signs and symptoms of heart failure or sudden cardiac death
      secondary to chronic myocardial ischemia. There have been an increasing number of
      reports of ALCAPA patients surviving to adulthood. There seems, however, to be a
      tendency to die suddenly in the third decade of life. Adult survivors are either
      asymptomatic or present with mitral regurgitation, cardiomyopathy, myocardial
      ischemia, or malignant arrhythmias. The management of the older patient
      presenting with symptoms resulting from ischemia and progressive left ventricular
      dysfunction remains a challenge. Treatment is largely based on guidelines for
      adult congenital heart disease management and an extrapolation of evidence from
      heart failure practice. Currently, surgical reimplantation of the anomalous
      coronary onto the aorta is the mainstay of treatment. The management of heart
      failure, sudden cardiac death, and ventricular arrhythmia present problems that
      are not addressed by reimplantation of the anomalous vessel alone. In this
      report, we present two cases with different modes of presentation and discuss
      treatment options. 

PMID- 23953780
TI  - In-vivo quantitative T2 mapping of carotid arteries in atherosclerotic patients:
      segmentation and T2 measurement of plaque components.
AB  - BACKGROUND: Atherosclerotic plaques in carotid arteries can be characterized in
      vivo by multicontrast cardiovascular magnetic resonance (CMR), which has been
      thoroughly validated with histology. However, the non-quantitative nature of
      multicontrast CMR and the need for extensive post-acquisition interpretation
      limit the widespread clinical application of in-vivo CMR plaque characterization.
      Quantitative T2 mapping is a promising alternative since it can provide absolute
      physical measurements of plaque components that can be standardized among
      different CMR systems and widely adopted in multi-centre studies. The purpose of
      this study was to investigate the use of in-vivo T2 mapping for atherosclerotic
      plaque characterization by performing American Heart Association (AHA) plaque
      type classification, segmenting carotid T2 maps and measuring in-vivo T2 values
      of plaque components. METHODS: The carotid arteries of 15 atherosclerotic
      patients (11 males, 71 +/- 10 years) were imaged at 3 T using the conventional
      multicontrast protocol and Multiple-Spin-Echo (Multi-SE). T2 maps of carotid
      arteries were generated by mono-exponential fitting to the series of images
      acquired by Multi-SE using nonlinear least-squares regression. Two reviewers
      independently classified carotid plaque types following the CMR-modified AHA
      scheme, one using multicontrast CMR and the other using T2 maps and time-of
      flight (TOF) angiography. A semi-automated method based on Bayes classifiers
      segmented the T2 maps of carotid arteries into 4 classes: calcification, lipid
      rich necrotic core (LRNC), fibrous tissue and recent IPH. Mean +/- SD of the T2
      values of voxels classified as LRNC, fibrous tissue and recent IPH were
      calculated. RESULTS: In 37 images of carotid arteries from 15 patients, AHA
      plaque type classified by multicontrast CMR and by T2 maps (+ TOF) showed good
      agreement (76% of matching classifications and Cohen's kappa = 0.68). The T2 maps
      of 14 normal arteries were used to measure T2 of tunica intima and media (T2 = 54
      +/- 13 ms). From 11865 voxels in the T2 maps of 15 arteries with advanced
      atherosclerosis, 2394 voxels were classified by the segmentation algorithm as
      LRNC (T2 = 37 +/- 5 ms) and 7511 voxels as fibrous tissue (T2 = 56 +/- 9 ms); 192
      voxels were identified as calcification and one recent IPH (236 voxels, T2 = 107
      +/- 25 ms) was detected on T2 maps and confirmed by multicontrast CMR.
      CONCLUSIONS: This carotid CMR study shows the potential of in-vivo T2 mapping for
      atherosclerotic plaque characterization. Agreement between AHA plaque types
      classified by T2 maps (+TOF) and by conventional multicontrast CMR was good, and
      T2 measured in-vivo in LRNC, fibrous tissue and recent IPH demonstrated the
      ability to discriminate plaque components on T2 maps.

PMID- 23953781
TI  - A review of the biomaterials technologies for infection-resistant surfaces.
AB  - Anti-infective biomaterials need to be tailored according to the specific
      clinical application. All their properties have to be tuned to achieve the best
      anti-infective performance together with safe biocompatibility and appropriate
      tissue interactions. Innovative technologies are developing new biomaterials and
      surfaces endowed with anti-infective properties, relying either on antifouling,
      or bactericidal, or antibiofilm activities. This review aims at thoroughly
      surveying the numerous classes of antibacterial biomaterials and the underlying
      strategies behind them. Bacteria repelling and antiadhesive surfaces, materials
      with intrinsic antibacterial properties, antibacterial coatings, nanostructured
      materials, and molecules interfering with bacterial biofilm are considered. Among
      the new strategies, the use of phages or of antisense peptide nucleic acids are
      discussed, as well as the possibility to modulate the local immune response by
      active cytokines. Overall, there is a wealth of technical solutions to contrast
      the establishment of an implant infection. Many of them exhibit a great potential
      in preclinical models. The lack of well-structured prospective multicenter
      clinical trials hinders the achievement of conclusive data on the efficacy and
      comparative performance of anti-infective biomaterials. 

PMID- 23953782
TI  - Cationic core-shell nanoparticles with carmustine contained within O6
      benzylguanine shell for glioma therapy.
AB  - The application of carmustine (BCNU) for glioma treatment is limited due to its
      poor selectivity for tumor and tumor resistance caused by O6-methylguanine-DNA
      methyl transferase (MGMT). To improve the efficacy of BCNU, we constructed
      chitosan surface-modified poly (lactide-co-glycolides) nanoparticles (PLGA/CS
      NPs) for targeting glioma, loading BCNU along with O6-benzylguanine (BG), which
      could directly deplete MGMT. With core-shell structure, PLGA/CS NPs in the
      diameter around 177 nm showed positive zeta potential. In vitro plasma stability
      of BCNU in NPs was improved compared with free BCNU. The cellular uptake of NPs
      increased with surface modification of CS and decreasing particle size. The
      cytotoxicity of BCNU against glioblastoma cells was enhanced after being
      encapsulated into NPs; furthermore, with the co-encapsulation of BCNU and BG into
      NPs, BCNU + BG PLGA/CS NPs showed the strongest inhibiting ability. Compared to
      free drugs, PLGA/CS NPs could prolong circulation time and enhance accumulation
      in tumor and brain. Among all treatment groups, F98 glioma-bearing rats treated
      with BCNU + BG PLGA/CS NPs showed the longest survival time and the smallest
      tumor size. The studies suggested that the co-encapsulation of BCNU and BG into
      PLGA/CS NPs could remarkably enhance the efficacy of BCNU, accompanied with
      greater convenience for therapy.

PMID- 23953783
TI  - [Fluid overload and arterial hypertension in hemodialysis patients].
AB  - The water sodium overload is a factor of morbi-mortality and its treatment is one
      of the markers of adequacy of the hemodialysis treatment. Its first clinical
      assessment was improved by tools such as echocardiography and ultrasonography of
      the inferior vena cava, the per-dialytic curve of plasma volume, measuring BNP or
      proBNP and by impedancemetry. The combination of the evaluation of these
      parameters and of the clinical situation allows one to assess the extracellular
      overload, the state of the blood volume and the potential of plasma refilling.
      The latter is a key factor of the per-dialytic hemodynamic tolerance. It is
      itself a determining factor in weight can be achieved at the end of the session.
      Getting the "dry" weight can require modifications of the prescriptions of the
      hemodialysis sessions, a filling by albumin even a drugs support. Finally, the
      overload treatment is the central part of the treatment of arterial hypertension,
      which has to benefit however often from antihypertensive treatment the profit of
      which is demonstrated. 

PMID- 23953784
TI  - Long-term patient perception of pain control experience after participating in a
      trial between patient-controlled analgesia and epidural after pectus excavatum
      repair with bar placement.
AB  - BACKGROUND: Pain control is the dominant management issue after bar placement for
      pectus excavatum. We previously conducted a prospective, randomized trial
      comparing patient-controlled analgesia (PCA) to thoracic epidural (EPI)
      documenting similar objective outcomes. Our impression is that the subjective
      cognitive experience differs between the groups, which impacts trial results
      interpretation. Therefore, we conducted a survey to ascertain patient
      recollection and impression of their experience. METHODS: By telephone
      questionnaire, yes/no questions included early course recall, anxiety, if they
      would choose the same arm, do the operation again, or recommend it to friends.
      Qualitative questions included description, location, and time of peak pain. The
      graded question addressed severity of pain (1-5). RESULTS: We contacted 27 EPI
      and 38 PCA patients with a median follow-up of 3.2 y. The majority (~/= 85%) of
      both groups remembered the first 2 d. Mean pain severity was 3.0 in both groups
      (3 = bad, but tolerable). Description, location, and time of peak pain responses
      did not differ. Anxiety was reported by 30% of EPI group and 18% of PCA group (P
      = 0.37). Approximately 15% of both groups still think about the pain. No
      differences were seen in nausea, emesis, constipation, itching, or sleepiness.
      Most patients would choose the same group (87% PCA, 81% EPI, P = 0.73), have the
      operation again (87% PCA, 74% EPI, P = 0.21), and recommend the operation to
      friends (100% PCA, 96% EPI, P = 0.42). CONCLUSIONS: Long-term recall after repair
      of pectus excavatum with bar placement does not substantially differ between
      those managed with an epidural or PCA.

PMID- 23953785
TI  - Attributes of a surgical chairperson associated with extramural funding of a
      department of surgery.
AB  - BACKGROUND: Chairpersons of surgery departments are key stakeholders and role
      models and leaders of research in academic medical institutions. However, the
      characteristics of surgical chairpersons are understudied. This study aimed to
      investigate the association between the personal academic achievement of a
      surgical chairperson and the National Institutes of Health (NIH) funding of the
      department. METHODS: We calculated the Hirsch index (H-index), a measure of
      research productivity, for chairpersons of surgery of the top 90 research medical
      schools that were ranked by U.S. News & World Report. Specialty training, y as
      chairperson, location, and NIH institutional and department funding were
      analyzed. Nonparametric tests and linear regression methods were used to compare
      the different groups. RESULTS: Of the 90 chairpersons, 20 positions for chairs
      (22%) are either recent (<1 y) or unfilled (n = 6). Only 3% of all chairpersons
      are women, and the median H-index for the chairpersons is 20 (Interquartile range
      14-27) with a median 101 publications with 14 cites per publication. Median
      surgery-specific NIH funding in 2011 was $1.7 million (Interquartile range
      $721,042-5,085,305). The chairperson's H-index was exponentially associated with
      department funding in multivariate models adjusting for institution rank, except
      when the H-index was extreme (<4 or >49) (coefficient 0.32, P = 0.02).
      CONCLUSIONS: The research productivity of a chairperson is the only personal
      attribute of those studied that is associated with the departmental NIH funding.
      This suggests the important role an academically productive surgical leader may
      play as a champion for the academic success of the department.

PMID- 23953786
TI  - Results of carotid angioplasty and stenting are equivalent for critical versus
      high-grade lesions in patients deemed high risk for carotid endarterectomy.
AB  - BACKGROUND: To examine outcomes of carotid angioplasty and stenting (CAS) in
      patients with critical carotid stenosis who are deemed high risk for carotid
      endarterectomy. METHODS: Medical records were retrospectively analyzed for
      patients undergoing CAS between September 2002 and March 2011 at a single
      institution. Patients were classified as having either critical (>= 90%) or high
      grade (70%-89%) carotid stenosis based on angiography. The primary composite end
      point was stroke, myocardial infarction, or death from any cause during the
      periprocedural period or any ipsilateral stroke during the follow-up period.
      RESULTS: A total of 245 patients underwent 257 CAS procedures during the study
      period. Fifty-one percentage (n = 130) of cases involved critical stenosis (66.2%
      male; mean age, 71 +/- 10 y), with the remaining group (n = 127) involving high
      grade stenosis (67.7% male; mean age, 71 +/- 9 y). Symptomatic carotid disease
      was present in 25% of the critical stenosis and 31% of the high-grade stenosis
      groups (P = 0.33). Chronic obstructive pulmonary disease was more commonly found
      in the high-grade stenosis group (20% versus 8%, P = 0.01). No difference was
      observed between the groups relative to other baseline demographic
      characteristics, presence of contralateral carotid occlusion, stent diameter or
      length, maximum balloon diameter or length, use of embolic protection device, or
      procedural duration. Technical success was achieved in all cases. There was no
      difference in the need to predilate before the introduction of the filter or
      stent based on the degree of stenosis. We found no difference in the primary
      composite end point between the high-grade or critical stenosis groups (7.1%
      versus 7.7%, P = 0.74), or there were no differences between the individual
      components of the composite end point. Mid-term survival was similar between the
      two groups at a mean follow-up period of 2.4 y. CONCLUSIONS: Despite concerns
      regarding the potential for increased neurologic complications, our data
      demonstrate that patients with high-grade and critical stenosis are able to
      safely undergo CAS and achieve similar periprocedural outcomes and mid-term
      prognosis.

PMID- 23953787
TI  - Comparison of short- and long-term outcomes after early versus late liver
      retransplantation: a single-center experience.
AB  - BACKGROUND: As the survival of patients after liver transplantation (LT)
      improves, the requirement of liver retransplantation (reLT) for late graft
      failure has grown. Although some have reported that the short-term outcome of
      late reLT was comparable with that of early reLT, it remains unknown whether long
      term survival of late reLT is inferior to that of early reLT patients. MATERIALS
      AND METHODS: We reviewed early (<6 mo after primary LT) and late (>=6 mo after
      primary LT) reLT cases performed between January 2000 and December 2010. RESULTS:
      Sixteen early and 32 late reLT cases were analyzed. There was no significant
      difference regarding the number of units of red blood cells transfused during the
      transplantation between the groups, whereas operative time was significantly
      longer in the late reLT cases. Graft loss within 3 mo after early and late reLT
      was 18.6% and 15.6%, respectively. Patient and graft survival rates after 1, 3,
      5, and 10 y in the late reLT group were 80.6%, 73.3%, 73.3%, and 67.7% and 80.7%,
      69.1%, 63.3%, and 54.3%, respectively, whereas those in the early reLT group were
      75.0%, 75.0%, 64.3%, and 64.3% and 81.3%, 75.0%, 64.3%, and 32.1%, respectively.
      There was no significant difference in patient or graft survival rates between
      the groups (P = 0.91 and 0.91, respectively). CONCLUSIONS: Acceptable short- and
      long-term survival were provided in early and late reLT. The time between the
      primary LT and reLT does not seem to play significant role in the prognosis of
      reLT in the long term.

PMID- 23953788
TI  - Remote ischemic perconditioning protects the liver from ischemia-reperfusion
      injury.
AB  - BACKGROUND: Ischemia-reperfusion (IR)-induced injury is a frequent sequel of
      major liver resections. IR injury after prolonged surgical interventions could be
      the source of increased risk of postoperative morbidity and mortality.
      Hepatoprotective effects of this new feasible method called remote ischemic
      perconditioning (RIPER) were investigated in our rat model of IR injury.
      MATERIALS AND METHODS: Male Wistar rats underwent ischemia for 60 min on two
      thirds of their livers, followed by 1, 6, and 24 h of reperfusion (n = 72, 8 per
      group). During liver ischemia, but before reperfusion, rats in the treated groups
      received four cycles of brief infrarenal aortic clamping as perconditioning.
      Liver microcirculation was monitored by laser Doppler flowmeter parallel with
      mean arterial pressure measurements. Liver tissue injury and redox homeostasis
      were investigated. Furthermore, serum tumor necrosis factor alpha (TNF-alpha)
      levels were measured. RESULTS: In the RIPER group, compared with the IR group,
      serum transaminase levels were significantly lower after each reperfusion period
      (alanine aminotransferase: 1 h, P < 0.001; 6 h, P < 0.05; 24 h, P < 0.01 and
      aspartate aminotransferase: 1 h, P < 0.001; 6 h, P < 0.05; 24 h, P < 0.05).
      Reperfusion microcirculatory parameters significantly improved in the
      perconditioned group compared with those in the IR group (reperfusion area: P =
      0.005; maximal plateau: P = 0.0002). Regarding TNF-alpha levels, significant
      differences were detected between the two IR injured groups (RIPER versus IR: 1
      h, 34.3 +/- 12.8 pg/mL versus 205.7 +/- 60.9 pg/mL, P < 0.001; 6 h, 60.6 +/- 11.7
      pg/mL versus 110.4 +/- 21.6 pg/mL, P < 0.05). Results of the histologic
      assessment and redox state measurements also showed favorable changes.
      CONCLUSIONS: Our team firstly reported the protective effects of RIPER on liver
      morphology, redox homeostasis, and microcirculation and proposed the changes of
      TNF-alpha expression.

PMID- 23953789
TI  - The effects of propofol and dexmedetomidine infusion on fluid responsiveness in
      critically ill patients.
AB  - BACKGROUND: We studied the effects of propofol or dexmedetomidine on preload
      dependency and fluid responsiveness in critically ill patients. METHODS: In the
      study, we included 91 patients with acute circulatory failure (70 +/- 15 y) who
      received propofol (n = 45 patients, PROP group) or dexmedetomidine (n = 46
      patients, DEX group). An initial passive leg-raising (PLR 1) test was performed
      in all patients to evaluate preload dependency at baseline. Propofol and
      dexmedetomidine were infused and titrated according to the Richmond Agitation
      Sedation Scale; the results ranged from -2 to -1, and the bispectral index values
      ranged from 60-75. A second PLR test (PLR 2) was performed before administration
      of a 250-mL normal saline fluid challenge over a 5-min period. We obtained
      central venous pressure and cardiac index (CI) measurements before and after the
      two PLR tests and volume expansion. An increase of >=10% in CI during PLR was
      considered to be a positive test finding that was indicative of preload
      dependency, whereas an increase of <10% in CI during PLR was considered to be a
      negative test finding. RESULTS: At baseline, 22 of 45 patients had negative PLR 1
      in the PROP group, whereas 20 of 46 patients had negative PLR 1 in the DEX group.
      After propofol or dexmedetomidine sedation, there were significant decreases in
      CI (-9.5% [+/-6.6%] versus -16.4% [+/-8.5%], P < 0.001) in the PROP and DEX
      groups, respectively. In the PROP group, there were significant increases in CI
      (+18.4% [+/-9.5%] versus +10.7% [+/-12.3%], P < 0.05) induced by PLR 2 compared
      with that induced by PLR 1. In the DEX group, there were no significant increases
      in CI (+13.2% [+/-14.9%] versus +12.8% [+/-17.7%]) induced by PLR 2 compared with
      that induced by PLR 1. Although the mean arterial pressure values increased
      comparably with the volume expansion observed in both groups, the volume
      expansion resulted in a significantly higher increase in CI compared with the
      baseline values in the PROP group (3.2 +/- 0.8 versus 3.2 +/- 0.7 L/min/m(2)) but
      not in the DEX group (2.9 +/- 0.7 versus 3.1 +/- 0.8 L/min/m(2), P < 0.05).
      CONCLUSIONS: We observed that propofol infusion, but not dexmedetomidine
      infusion, can increase preload dependency and fluid responsiveness in patients
      with circulatory failure.

PMID- 23953790
TI  - Transplantation of expanded endothelial colony-forming cells improved outcomes of
      traumatic brain injury in a mouse model.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) are critical for repairing
      injured tissue. Endothelial colony-forming cells (ECFCs) are a homogeneous
      subtype of EPCs. We investigated whether intravenously infused human ECFCs homed
      to injured brain promoted angiogenesis and ameliorate neurologic disabilities in
      a mouse model of traumatic brain injury. MATERIALS AND METHODS: ECFCs were
      generated by in vitro propagation of EPCs from human umbilical cord blood. Young
      female nude mice received intravenously ECFCs from human newborns (1 * 10(6)) 1 h
      after they were exposed to lateral fluid percussion injury. Neurologic function
      was evaluated by a modified neurologic severity score and Morris water maze. ECFC
      homing and neovascularization at the site of injury were examined by fluorescence
      in situ hybridization and histochemistry on days 2 and 14 after injury,
      respectively. RESULTS: Donor ECFCs were detected in injured brain 24 h after
      infusion. The modified neurologic severity score and Morris water maze tests were
      used to evaluate neurologic disability, and found the rate of neurologic
      disability was improved in mice that received ECFCs. Microvessel density and
      expression of the proangiogenic growth factors stromal cell-derived factor-1 and
      vascular endothelial growth factor were also increased in the region of injured
      brain from mice that received ECFCs compared with those received vehicle control.
      CONCLUSIONS: These data suggest that ECFCs are effective in promoting
      neovascularization and improving neurologic functions after traumatic brain
      injury.

PMID- 23953791
TI  - Atrial natriuretic peptide attenuates kidney-lung crosstalk in kidney injury.
AB  - BACKGROUND: Renal ischemia-reperfusion injury (IRI) is a common cause of acute
      kidney injury after cardiovascular surgery, which in turn deteriorates
      oxygenation. Atrial natriuretic peptide (ANP) has natriuretic, diuretic, and anti
      inflammatory effects. To elucidate whether renal IRI induces inflammation in the
      kidney and lung and ANP attenuates kidney-lung crosstalk. MATERIALS AND METHODS:
      The rats were anesthetized, tracheostomized, mechanically ventilated, and
      randomized to four groups: saline + IRI (n = 12), ANP + IRI (n = 12), ANP + sham
      (n = 6), and saline + sham (n = 6). Saline (6 mL/kg/h) or ANP (0.2 MUg/kg/min) at
      the rate of 6 mL/kg/h was started 5 min before clamping, respectively. Renal IRI
      was induced by clamping the left renal pedicle for 30 min. The hemodynamics,
      arterial blood gases, and plasma concentrations of creatinine and lactate were
      measured at baseline and 1, 2, and 3 h after declamping. Lung wet-to-dry ratio
      was measured. The mRNA expression of tumor necrosis factor (TNF)-alpha,
      interleukin (IL) 1beta, and IL-6 and histologic localization of TNF-alpha in the
      kidney and lung were measured. RESULTS: Renal IRI induced metabolic acidosis,
      pulmonary edema, increases in plasma concentrations of creatinine and lactate,
      and augmentation of the cytokine mRNA expression and histologic localization of
      TNF-alpha in the kidney and Renal IRI induced lung. ANP prevented IRI-induced
      metabolic acidosis, pulmonary edema, increases in creatinine, lactate, and the
      cytokine mRNA expression, attenuated histologic localization of TNF-alpha in the
      kidney and lung, and increased oxygenation. CONCLUSIONS: ANP has renoprotective
      and anti-inflammatory effects on the kidney and lung in a rat model of renal IRI,
      suggesting that ANP attenuates kidney-lung crosstalk.

PMID- 23953792
TI  - Bacterial translocation induces proinflammatory responses and is associated with
      early death in experimental severe injury.
AB  - OBJECTIVE: An experimental model of severe injury with great lethality was
      studied to define the impact of bacterial translocation on survival and on
      inflammatory response. METHODS: Forty-one rabbits were divided into two groups:
      A, femur myotomy; and B, myotomy and fracture of the femoral bone. Vital signs
      and survival were recorded. Serum circulating endotoxins (lipopolysaccharides;
      LPS) were determined and tissue cultures were performed at necropsy. A subgroup
      of animals was sacrificed at 48 h post injury; LPS was determined in abdominal
      aorta and portal vein, apoptosis of spleen cells was assessed by flow cytometry,
      and ex vivo production of tumor necrosis factor alpha by splenocytes was
      measured. RESULTS: Tissue bacterial burden was increased in animals that died
      early (i.e., within 48 h after injury) versus rabbits that died later. Portal
      vein LPS at 48 h was increased in group B compared with group A, whereas
      circulating LPS did not differ. No difference in apoptosis of either lymphocytes
      or macrophages of the spleen was found in group B compared with group A.
      Following stimulation with LPS or phytohemagglutinin, tumor necrosis factor alpha
      production by splenocytes of group B was greater than that of group A.
      CONCLUSIONS: Bacterial translocation primes enhanced proinflammatory responses
      and it is associated with early death in severe trauma.

PMID- 23953794
TI  - Clinical evaluation and optimal management of cancer cachexia.
AB  - Cancer anorexia-cachexia syndrome (CACS) is a complex metabolic syndrome,
      different from malnutrition and sarcopenia, which is very common in cancer
      patients. Treatment for CACS is based on nutritional support and CACS
      pathophysiology-modulating drugs. The most commonly used are megestrol acetate
      (MA) and corticosteroids. The efficacy of MA has been confirmed by multiple
      clinical trials and meta-analyses. Glucocorticoids are also effective but should
      only be used for short periods and in selected cases. Future strategies should
      include intensified research into potentially effective drugs (omega-3 fatty
      acids, thalidomide, cannabinoids, ghrelin, bortezomib, and COX-2 inhibitors),
      combined treatment and new drugs (anti-IL-6 monoclonal antibodies, melanocortin,
      beta-2 antagonists, and androgen receptor-modulating analogues). We propose a
      review based on the literature on the pathophysiology of CACS, the diagnostic
      criteria and treatment, and future strategies.

PMID- 23953793
TI  - Pretreatment with sildenafil alleviates early lung ischemia-reperfusion injury in
      a rat model.
AB  - BACKGROUND: Lung ischemia-reperfusion (I/R) injury plays an important role in
      lung transplantation. Less well known is the role of sildenafil in lung I/R
      injury; therefore, we attempted to determine whether sildenafil could alleviate
      lung apoptosis and tissue injury in a rat model. METHODS: Forty male Sprague
      Dawley rats were randomized into four groups: saline + sham, saline + I/R,
      sildenafil + sham, and sildenafil + I/R groups. Three hours before the operation,
      each rat received normal saline or sildenafil (10 mg/kg) by lavage. The animals
      designed to I/R injury were subjected to 2 h of ischemia induced by occlusion of
      left pulmonary artery, veins, and bronchus, followed by reperfusion for 2 h. The
      lung tissue was harvested for the analysis of the expression of Bax, Bcl-2, p53,
      caspase 3, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and wet/dry
      (W/D) weight ratio. RESULTS: Compared with the saline + sham group, the saline +
      I/R group had significant increases in Bax, p53, Bax/Bcl-2 ratio, caspase 3, IL
      6, TNF-alpha, and W/D weight ratio but a decrease in Bcl-2 (P < 0.05). Compared
      with the saline + I/R group, sildenafil + I/R group had significant decreases in
      Bax, p53, Bax/Bcl-2 ratio, caspase 3, IL-6, TNF-alpha level, and W/D weight ratio
      but an increase in Bcl-2 expression (P < 0.05). Compared with the sildenafil +
      sham group, there were significant increases in p53 and TNF-alpha expression in
      the sildenafil + I/R group (P < 0.05). CONCLUSIONS: Pretreatment with sildenafil
      alleviates lung apoptosis and tissue injury in a rat model.

PMID- 23953795
TI  - Salvage therapy of intraprostatic failure after radical external-beam
      radiotherapy for prostate cancer: a review.
AB  - Radical external-beam radiotherapy (EBRT) is a standard treatment for prostate
      cancer (PC) patients. Despite this, the rate of intraprostatic relapses after
      primary EBRT is still not negligible. There is no consensus on the most
      appropriate management of these patients after EBRT failure. Treatment strategies
      after PC relapse are strongly influenced by the effective site of the tumor
      recurrence, and thus the instrumental evaluation with different imaging
      techniques becomes crucial. In cases of demonstrated intraprostatic failure,
      several systemic (androgen deprivation therapy) or local (salvage prostatectomy,
      cryotherapy, high-intensity focused ultrasound, brachytherapy, stereotactic EBRT)
      treatment options could be proposed and are currently delivered by clinicians
      with a variety of results. In this review we analyze the correct definition of
      intraprostatic relapse after radiotherapy, focusing on the recent developments in
      imaging to detect intraprostatic recurrence. Furthermore, all available salvage
      treatment options after a radiation therapy local failure are presented and
      thoroughly discussed. 

PMID- 23953796
TI  - Introduction: potassium homeostasis in humans: our current understanding.

PMID- 23953798
TI  - Renal potassium homeostasis: a short historical perspective.
AB  - During the past century, investigators have increased our understanding of renal
      potassium excretion significantly using many techniques. Notable among these were
      renal clearance experiments, renal micropuncture, isolated tubule microperfusion,
      and electrophysiological and patch clamp analysis. These experiments have been
      made possible by technical advances that have allowed the measurement of
      potassium in progressively smaller quantities. Initially, the kidney was viewed
      as controlling potassium excretion by the regulated absorption of potassium from
      the glomerular filtrate, predominantly in the proximal tubule. This concept was
      supplanted when clearance experiments deduced and subsequent micropuncture
      studies directly identified the importance of the distal nephron and collecting
      duct as the principal site responsible for the regulation of potassium excretion.
      Additional micropuncture and microperfusion studies showed that a component of
      potassium secreted by the distal cortical nephron and cortical collecting duct is
      reabsorbed in the medullary collecting duct, which results in renal medullary
      potassium recycling. Studies have defined the cellular and molecular mechanisms
      responsible for potassium secretion and potassium reabsorption in the collecting
      duct. Further understanding of renal potassium handling will require integrated
      investigation of the renal and extrarenal signaling systems that control these
      transport mechanisms. 

PMID- 23953799
TI  - Regulation of renal potassium secretion: molecular mechanisms.
AB  - A new understanding of renal potassium balance has emerged as the molecular
      underpinnings of potassium secretion have become illuminated, highlighting the
      key roles of apical potassium channels, renal outer medullary potassium channel
      (ROMK) and Big Potassium (BK), in the aldosterone-sensitive distal nephron and
      collecting duct. These channels act as the final-regulated components of the
      renal potassium secretory machinery. Their activity, number, and driving forces
      are precisely modulated to ensure potassium excretion matches dietary potassium
      intake. Recent identification of the underlying regulatory mechanisms at the
      molecular level provides a new appreciation of the physiology and reveals a
      molecular insight to explain the paradoxic actions of aldosterone on potassium
      secretion. Here, we review the current state of knowledge in the field. 

PMID- 23953800
TI  - Role of circadian rhythms in potassium homeostasis.
AB  - It has been known for decades that urinary potassium excretion varies with a
      circadian pattern. In this review, we consider the historical evidence for this
      phenomenon and present an overview of recent developments in the field. Extensive
      evidence from the latter part of the past century clearly shows that circadian
      potassium excretion does not depend on endogenous aldosterone. Of note is the
      recent discovery that the expression of several renal potassium transporters
      varies with a circadian pattern that appears to be consistent with substantial
      clinical data regarding daily fluctuations in urinary potassium levels. We
      propose the circadian clock mechanism as a key regulator of renal potassium
      transporters, and consequently renal potassium excretion. Further investigation
      into the regulation mechanism of renal potassium transport by the circadian clock
      is warranted to increase our understanding of the clinical relevance of circadian
      rhythms to potassium homeostasis. 

PMID- 23953801
TI  - Extracellular potassium homeostasis: insights from hypokalemic periodic
      paralysis.
AB  - Extracellular potassium makes up only about 2% of the total body's potassium
      store. The majority of the body potassium is distributed in the intracellular
      space, of which about 80% is in skeletal muscle. Movement of potassium in and out
      of skeletal muscle thus plays a pivotal role in extracellular potassium
      homeostasis. The exchange of potassium between the extracellular space and
      skeletal muscle is mediated by specific membrane transporters. These include
      potassium uptake by Na(+), K(+)-adenosine triphosphatase and release by inward
      rectifier K(+) channels. These processes are regulated by circulating hormones,
      peptides, ions, and by physical activity of muscle as well as dietary potassium
      intake. Pharmaceutical agents, poisons, and disease conditions also affect the
      exchange and alter extracellular potassium concentration. Here, we review
      extracellular potassium homeostasis, focusing on factors and conditions that
      influence the balance of potassium movement in skeletal muscle. Recent findings
      that mutations of a skeletal muscle-specific inward-rectifier K(+) channel cause
      hypokalemic periodic paralysis provide interesting insights into the role of
      skeletal muscle in extracellular potassium homeostasis. These recent findings are
      reviewed. 

PMID- 23953802
TI  - Gut sensing of potassium intake and its role in potassium homeostasis.
AB  - Extracellular K(+) homeostasis has been explained by feedback mechanisms in which
      changes in extracellular K(+) concentration drive renal K(+) excretion directly
      or indirectly via stimulating aldosterone secretion. However, this cannot explain
      meal-induced kaliuresis, which often occurs without increases in plasma K(+) or
      aldosterone concentrations. Recent studies have produced evidence supporting a
      feedforward control in which gut sensing of dietary K(+) increases renal K(+)
      excretion (and extrarenal K(+) uptake) independent of plasma K(+) concentrations,
      namely, a gut factor. This review focuses on these new findings and discusses the
      role of gut factor in acute and chronic regulation of extracellular K(+) as well
      as in the beneficial effects of high K(+) intake on the cardiovascular system. 

PMID- 23953803
TI  - Acid-base and potassium homeostasis.
AB  - Acid-base balance and potassium disorders are often clinically linked.
      Importantly, acid-base disorders alter potassium transport. In general, acidosis
      causes decreased K(+) secretion and increased reabsorption in the collecting
      duct. Alkalosis has the opposite effects, often leading to hypokalemia. Potassium
      disorders also influence acid-base homeostasis. Potassium depletion causes
      increased H(+) secretion, ammoniagenesis and H-K-ATPase activity. Hyperkalemia
      decreases ammoniagenesis and NH4(+) transport in the thick ascending limb. Some
      combined potassium and acid-base disorders involve indirect factors such as
      aldosterone, impaired renal function, volume depletion, and diarrhea. In summary,
      disorders of potassium and acid-base homeostasis are mechanistically linked and
      clinically important. 

PMID- 23953805
TI  - Potassium in hypertension and cardiovascular disease.
AB  - The increased prevalence of hypertension and cardiovascular disease in
      industrialized societies undoubtedly is associated with the modern high
      sodium/low-potassium diet. Extensive experimental and clinical data strongly link
      potassium intake to cardiovascular outcome. Most studies suggest that the sodium
      to-potassium intake ratio is a better predictor of cardiovascular outcome than
      either nutrient individually. A high-sodium/low-potassium environment results in
      significant abnormalities in central hemodynamics, leading to potential target
      organ damage. Altered renal sodium handling, impaired endothelium-dependent
      vasodilatation, and increased oxidative stress are important mediators of this
      effect. It remains of paramount importance to reinforce consumption of a low
      sodium/high-potassium diet as a critical strategy for prevention and treatment of
      hypertension and cardiovascular disease. 

PMID- 23953806
TI  - Chronic renal disease progression: treatment strategies and potassium intake.
AB  - Disordered potassium homeostasis is a common complication of chronic kidney
      disease and traditional management focuses on restricting potassium intake to
      avoid hyperkalemia. Permissive potassium intake carries the risk of hyperkalemia
      and hyperphosphatemia, and possibly may contribute to the development of uremic
      neuropathy. Excessive potassium restriction and removal by dialysis carries the
      risk of worsened chronic hypertension, intradialytic hypotension, renal fibrosis
      and cyst formation, and ventricular arrhythmias. Cohort studies have associated
      both hypokalemia and hyperkalemia with increased mortality in CKD. A single study
      of potassium intake in hemodialysis patients found increased intake associated
      with increased mortality despite adjustment for serum potassium concentration. We
      recommend avoiding mandatory potassium restriction in early chronic kidney
      disease. We endorse routine potassium restriction in advanced chronic kidney
      disease requiring hemodialysis and close monitoring of serum potassium
      concentration in any patients receiving renin-angiotensin-aldosterone system
      blockers. 

PMID- 23953804
TI  - Endocrine and hypertensive disorders of potassium regulation: primary
      aldosteronism.
AB  - The identification of primary aldosteronism as a common cause of resistant
      hypertension is a significant advance in our ability to care for patients with
      hypertension. Primary aldosteronism is common, and when unrecognized is
      associated with an increased incidence of adverse cardiovascular outcomes.
      Identification of primary aldosteronism is based on use of the plasma aldosterone
      level, plasma renin activity, and the aldosterone:renin ratio. Differentiation
      between unilateral and bilateral autonomous adrenal aldosterone production then
      guides further therapy, with use of mineralocorticoid-receptor blockers for
      patients with bilateral autonomous adrenal aldosterone production and
      laparoscopic adrenalectomy for patients with unilateral autonomous aldosterone
      production. In this review, we discuss in detail the pathogenesis of primary
      aldosteronism-induced hypertension and potassium disorders, the evaluation of the
      patient with suspected primary aldosteronism, and the management of primary
      aldosteronism, both through medications and surgery. 

PMID- 23953807
TI  - Genetic disorders of potassium homeostasis.
AB  - Hereditary disorders of potassium homeostasis are an interesting group of
      disorders, affecting people from the newborn period to adults of all ages. The
      clinical presentation varies from severe hypotension at birth to uncontrolled
      hypertension in adults, often associated with abnormal potassium values, although
      many patients may have a normal serum potassium concentration despite being
      affected by the genetic disorder. A basic understanding of these disorders and
      their underlying mechanisms has significant clinical implications, especially in
      the few patients with subtle clinical signs and symptoms. We present a summary of
      these disorders, with emphasis on the clinical presentation and genetic
      mechanisms of these disorders. 

PMID- 23953808
TI  - Variability in the immune system: of vaccine responses and immune states.
AB  - System-wide approaches are now being applied to study vaccine responses, whose
      mechanisms of action, and failure, are not well understood. These works have
      repeatedly shown vaccine response to be an orchestrated process involving
      multiple arms of immunity most noticeable sensing and innate components.
      Prediction of vaccine responses based on system-wide measures is achievable, but
      challenges remain for robust population wide predictions based only on pre
      vaccination measures, especially in partially efficacious vaccines such as
      influenza. This is especially true in older adults, who are often less responsive
      to vaccination and exhibit high level of variation compared to young in many
      components of immunity. Despite this increase in variation, most of the studies
      on aging use group averages of immune phenotypes to model immune system behavior.
      Using systems approaches, it is possible to exploit this variation to form
      distinguishable clusters of phenotypes within and across individuals to discover
      underlying immune states. 

PMID- 23953809
TI  - Image-guided brachytherapy for cervical cancer: analysis of D2 cc hot spot in
      three-dimensional and anatomic factors affecting D2 cc hot spot in organs at
      risk.
AB  - PURPOSE: To analyze the D2 cc hot spot in three-dimensional CT and anatomic
      factors affecting the D2 cc hot spot in organs at risk (OARs). METHODS AND
      MATERIALS: Thirty-one patients underwent pelvic CT scan after insertion of the
      applicator. High-dose-rate treatment planning was performed with standard loading
      patterns. The D2 cc structures in OARs were generated in three dimensional if the
      total equivalent dose in 2 Gy exceeded our defined dose limits (hot spot). The
      location of D2 cc hot spot was defined as the center of the largest D2 cc
      fragment. The relationship between the hot spot and the applicator position was
      reported in Digital Imaging and Communication in Medicine coordinates. RESULTS:
      The location of sigmoid, small bowel, and bladder D2 cc hot spots was around the
      endocervix: The mean location of sigmoid hot spot for lateral view was 1.6 cm
      posteriorly and 2.3 cm superiorly (Y, 1.6 and Z, 2.3), small bowel was 1.6 cm
      anteriorly and 2.7 cm superiorly (Y, -1.6 and Z, 2.7). The mean location of
      bladder hot spot was 1.6 cm anteriorly and 1.6 cm superiorly (Y, -1.6 and Z,
      1.6). These hot spots were near the plane of Point A (X, 2.0 or -2.0; Y, 0; and
      Z, 2.0). The mean location of rectal hot spot was 1.6 cm posteriorly and 1.9 cm
      inferiorly (Y, 1.6 and Z, -1.9). D2 cc hot spot was affected by uterine wall
      thickness, uterine tandem position, fibroids, bladder fullness, bowel gas, and
      vaginal packing. CONCLUSIONS: Because of the location of the D2 cc hot spots,
      larger tumors present a challenge for adequate tumor coverage with a conventional
      brachytherapy applicator without an interstitial implant. Additionally, anatomic
      factors were identified which affect the D2 cc hot spot in OARs.

PMID- 23953811
TI  - Rebuttal to Drs. Spratt and Zelefsky.

PMID- 23953810
TI  - Complications after 90Y microsphere radioembolization for unresectable hepatic
      tumors: An evaluation of 112 patients.
AB  - PURPOSE: The aim of this study was to estimate the incidence of complications
      after (90)Y microsphere radioembolization for unresectable hepatic tumors and
      evaluate risk factors for late complications. METHODS AND MATERIALS: A cohort of
      112 consecutive patients from two institutions underwent (90)Y microsphere
      radioembolization for unresectable hepatic tumors. Complications were graded
      according to the Common Terminology Criteria for Adverse Events, version 3.0.
      Symptoms secondary to postradioembolization syndrome occurring within 30 days
      were recorded as early complications, and all other complications were considered
      late complications. RESULTS: Seventy-eight patients (70%) experienced
      postradioembolization syndrome, including fatigue, abdominal pain, nausea,
      vomiting, anorexia, or fever. Three patients (3%) experienced a Grade 3 early
      complication; no Grade 4 or 5 early toxicity occurred. Two patients (2%)
      experienced clinically significant liver dysfunction; 13 patients (12%), 27
      patients (24%), and 9 patients (8%) had an elevation of bilirubin, aspartate
      aminotransferase, and alanine aminotransferase, respectively. Eleven patients
      (10%) experienced gastrointestinal ulceration, including two Grade 3
      complications and one Grade 4 complication. Cholecystitis occurred in 7 patients
      (6%), including two Grade 3 complications. Grade 2 pancreatitis occurred in 1
      patient (1%). No radiation pneumonitis was observed. The cumulative incidence of
      late Grade 3 or 4 complications at 12 months after radioembolization was 8%. No
      Grade 5 toxicity occurred. CONCLUSIONS: (90)Y microsphere radioembolization is a
      well-tolerated treatment for unresectable hepatic tumors with a low risk of Grade
      3 or higher early or late toxicity.

PMID- 23953812
TI  - Pride or prejudice: does Phoenix flatter radiation therapy?
AB  - PURPOSE: To compare disease-free survival (DFS) rates using a >0.4 ng/mL
      biochemical failure definition with the Phoenix (nadir+2 ng/mL) failure
      definition by analyzing a consecutive cohort of 1006 patients treated with low
      dose-rate prostate brachytherapy (LDR-PB) monotherapy. METHODS AND MATERIALS:
      Data for first 1006 consecutive LDR-PB implants (1998-2003) were extracted from a
      prospective database. Patients had low- (58%) or intermediate (42%)-risk disease.
      Three months neoadjuvant and 3 months concomitant androgen deprivation therapy
      were used in 65% of cases. The Phoenix definition was modified to "unfail"
      patients who had a benign prostate-specific antigen (PSA) bounce. RESULTS: The
      median followup is 7.5 years. The median PSA at latest followup for disease-free
      patients was 0.04 ng/mL. The Phoenix definition yielded 5- and 10-year Kaplan
      Meier DFS estimates of 96.5 +/- 1.2% and 93.7 +/- 2.0%, respectively. Applying
      the >0.4 ng/mL threshold reduced these estimates to 94.4 +/- 1.6% and 88.8 +/-
      3.0% (log rank, p = 0.015). CONCLUSIONS: Compared with Phoenix, applying a >0.4
      ng/mL failure definition increased biochemical failure by ~2% at 5 years and ~5%
      at 10 years. These data show that Phoenix did not greatly exaggerate DFS
      estimates compared with a surgical-type threshold. However, this observation is a
      consequence of the exceptionally low residual PSA values characteristic of LDR-PB
      and cannot be generalized to other forms of radiation therapy.

PMID- 23953813
TI  - Different types of opioid receptors involved in the suppression of LH secretion
      in lactating sheep.
AB  - To learn the involvement of endogenous opioid peptides (EOP) in the regulation of
      reproductive activity in ruminants, the effects of different opioid antagonists
      on luteinizing hormone (LH) secretion were determined in sheep during the early
      stage of lactation. The opioid receptor antagonists: naloxone (all types of
      receptors, n=5), naloxonazine (MU receptor, n=5), GNTI- (kappa receptor, n=5),
      naltrindole (delta receptor, n=5) or the vehicle (control, n=5) were infused
      intracerebroventricularly in a series of five 30-min infusions (60MUg/60MUl) at
      30-min intervals. The period of the experiment included the non-suckling (10:00
      12.30) and suckling (12.30-15.00) periods. Blood samples were collected from
      10.00 to 15.00 at 10-min intervals, and plasma LH concentration was assayed by
      the radioimmunoassay method. The obtained results showed that blocking of the EOP
      action within the central nervous system in lactating sheep caused a significant
      (p<0.001) increase in LH concentration in all treated groups, in comparison to
      the control. In the naloxone-treated group, a significant (p<0.05) increase in LH
      secretion also occurred during suckling. The amplitude of LH pulses increased
      significantly in the naloxonazine- (p<0.01) and naltrindole- (p<0.05) treated
      ewes compared to the control; there were no significant differences in the
      frequency of LH pulses among the groups. In conclusion, our study indicates that
      EOP play a crucial role in the mechanism inhibiting GnRH/LH axis activity in
      lactating sheep and that the ligands for MU opioid receptor may have the highest
      inhibitory effect. 

PMID- 23953814
TI  - Size matching in lung transplantation: an evidence-based review.
AB  - The evidence base for size matching between donors and recipients in lung
      transplantation has not recently been reviewed in a comprehensive manner. Our aim
      in this study was to assimilate published studies that have addressed size
      matching of donors to recipients and to establish a pragmatic understanding of
      the range of lung sizes that may be used for lung transplantation. A
      comprehensive literature search was performed using Medline and PubMed up to and
      including September 2012, to identify scientific articles that relate to size
      matching between donors and lung transplant recipients. Seventy-two articles were
      identified, of which 21 had addressed the question of the impact of size
      mismatching on outcomes in lung transplantation. No study has specifically tested
      the consequences of intentionally mismatching above or below the hypothetical
      limits for double lung transplantation of a predicted total lung capacity for the
      donor of between 75% and 125% of the recipient predicted total lung capacity as
      set out in the ISHLT consensus report on lung donor acceptability criteria.
      Research is lacking that has robustly defined limits for size mismatch for single
      lung transplantation and for recipients with restrictive lung pathologies such as
      pulmonary fibrosis. Published research on the impact of size mismatching between
      lung transplant donors and recipients is limited by study design and size. It is
      centered on addressing the issue of mismatch in double lung transplantation in
      cohorts with a diagnostically heterogeneous make-up and in single lung transplant
      patients with chronic obstructive pulmonary disease. 

PMID- 23953815
TI  - The urgent priority for transplantation is to trim the waiting list.

PMID- 23953816
TI  - The Sarah Murnaghan debacle: a health policy perspective on transplant candidate
      selection.

PMID- 23953817
TI  - One-year experience with intravenous treprostinil for pulmonary arterial
      hypertension.
AB  - BACKGROUND: Intravenous (IV) epoprostenol has been the mainstay of therapy in
      advanced pulmonary arterial hypertension (PAH). Continuous IV treprostinil has
      several potential advantages over IV epoprostenol; however, there has been a lack
      of published long-term efficacy and safety data on IV treprostinil in PAH.
      METHODS: We conducted a 48-week, multicenter, prospective, open-label,
      uncontrolled, study of continuous IV treprostinil in 16 patients on no prior PAH
      specific therapy at baseline (de novo), or 31 patients transitioned at baseline
      from IV epoprostenol (transition). The primary end point was change in exercise
      capacity assessed by the 6-minute walk distance (6MWD) test. RESULTS: In de novo
      patients, IV treprostinil increased the mean +/- standard error 6MWD by 125 m
      from 332 +/- 21 m at baseline to 457 +/- 26 m at Week 48. There were also
      improvements in the secondary end points of Naughton-Balke treadmill time, Borg
      Dyspnea Score, and hemodynamics at Week 48 compared with baseline. In 23 patients
      transitioned from IV epoprostenol with 48-week follow-up data, 6MWD, hemodynamic
      measures, and World Health Organization functional class at Week 48 were all
      stable compared with baseline. Side effects were generally mild and consistent
      with those reported with prostacyclin treatment. During the study, 5 patients
      died of causes not considered related to the therapy, and 7 discontinued due to
      adverse events. CONCLUSIONS: In this open-label trial, continuous IV treprostinil
      for 1 year appears to be safe and effective in de novo PAH patients and those
      transitioned from IV epoprostenol.

PMID- 23953818
TI  - Experience of extracorporeal membrane oxygenation as a bridge to lung
      transplantation in France.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used as a
      bridge to lung transplantation (LTx). However, data concerning this approach
      remain limited. METHODS: We retrospectively reviewed the medical records of all
      patients in France who received ECMO as a bridge to LTx from 2007 to 2011. Post
      transplant survival and associated factors were assessed by the Kaplan-Meier
      method and the Cox model. RESULTS: Included were 36 patients from 11 centers.
      Indications for LTx were cystic fibrosis (CF) in 20 (56%), pulmonary fibrosis
      (PF) in 11 (30%), and other diagnoses in 5 (14%). ECMO was venovenous for 27
      patients (75%) and venoarterial for 9 (25%). Mean follow-up was 17 months.
      Bridging to LTx was achieved in 30 patients (83%); however, only 27 patients
      (75%) survived the LTx procedure, and 20 (56%) were discharged from hospital.
      From ECMO initiation, 2-year survival rates were 50.4% overall, 71.0% for CF
      patients, 27.3% for PF patients, and 20.0% for other patients (p < 0.001). From
      LTx, 2-year survival rates were 60.5% overall, 71.0% for CF patients, 42.9% for
      PF patients, and 33.0% for other patients (p = 0.04). CONCLUSIONS: Our study
      confirms that the use of ECMO as a bridge to LTx in France could provide a medium
      term survival benefit for LTx recipients with critical conditions. Survival
      differed by underlying respiratory disease. Larger studies are needed to further
      define the optimal use of ECMO.

PMID- 23953819
TI  - Prevention of airway allograft tolerance by polyinosinic:polycytidylic acid
      requires type I interferon responsiveness for mouse airway obliteration.
AB  - BACKGROUND: Respiratory RNA viruses are associated with bronchiolitis obliterans
      syndrome (BOS) in lung transplant recipients (LTRS); however, the immune
      mechanisms that regulate airway obliteration remain incompletely understood.
      METHODS: Using the mouse heterotopic tracheal transplant model of obliterative
      airway disease (OAD), we studied the role of double-stranded (ds)RNA using
      polyinosinic:polycytidylic acid (poly[I:C]), a synthetic analog of viral dsRNA,
      in abrogating airway allograft tolerance established with donor-specific
      transfusion (DST) and anti-CD154 monoclonal antibody therapy. RESULTS: Wild-type
      (WT) B6 recipients of accepted BALB/c airway grafts demonstrated significantly
      reduced intragraft CD8+ T cells, with markedly impaired allospecific interferon
      (INF)-gamma and tumor necrosis factor-alpha secretion, uncoupled from an
      activated phenotype, and evidence of proliferation. Administration of poly(I:C)
      to DST/anti-CD154-treated recipients restored OAD pathology and CD8+ alloeffector
      responses to levels observed in untreated mice. However, B6 type I IFN receptor
      deficient (IFN-alphabetaR(-/-)) recipients were resistant to the abrogation of
      tolerance mediated by poly(I:C) and did not develop CD8+ alloeffector responses
      or OAD. Further, adoptive transfers of WT CD8+ T cells or CD11c+ dendritic cells
      alone into B6 IFNalphabetaR(-/-) recipients treated with poly(I:C) and DST/anti
      CD154 were incapable of abrogating airway graft tolerance. CONCLUSIONS: Together,
      these data indicate abrogation of DST/anti-CD154-induced airway allograft
      tolerance via dsRNA requires type-I IFN responsiveness for mouse airway
      obliteration.

PMID- 23953821
TI  - Pulmonary meningothelial-like nodules are of donor origin in lung allografts.

PMID- 23953822
TI  - Heterotopic heart transplantation for elevated pulmonary vascular resistance in
      the current era: long-term clinical and hemodynamic outcomes.

PMID- 23953820
TI  - Modifications of skeletal muscle ryanodine receptor type 1 and exercise
      intolerance in heart failure.
AB  - BACKGROUND: In experimental heart failure animal models, remodeling of skeletal
      and cardiac muscle ryanodine receptors (RyR), including phosphorylation, S
      nitrosylation and oxidation, have been reported to contribute to pathologic Ca2+
      release, impaired muscle function and fatigue. However, it is not known whether
      similar remodeling of RyR1 in skeletal muscle occurs in patients with heart
      failure, and if this is associated with impairment of physical activity. METHODS:
      We studied 8 sedentary patients with New York Heart Association (NYHA) Class III
      heart failure and 7 age-matched, healthy, but sedentary controls. All heart
      failure patients had NYHA Class III and peak VO2, echocardiography and NT-proBNP
      data consistent with moderate to severe heart failure. The age-matched controls
      included were allowed hypertension but sub-clinical heart failure was to have
      been ruled out by normal peak VO2, echocardiography and NT-proBNP. RESULTS:
      Exercise capacity (VO2max) differed by almost 2-fold between heart failure
      patients and age-matched controls. Compared with controls, skeletal muscle RyR1
      in heart failure patients was excessively phosphorylated, S-nitrosylated and
      oxidized. Furthermore, RyR1 from heart failure patients was depleted of its
      stabilizing protein FK 506-binding protein 12 (FKBP12, or calstabin1).
      CONCLUSIONS: For the first time we show that skeletal muscle RyR1 from human
      heart failure is post-translationally modified, which corroborates previous data
      from experimental animal studies. This indicates pathologic Ca2+ release as a
      potential mechanism behind skeletal muscle weakness and impaired exercise
      tolerance in patients with heart failure and suggests a potential target for
      pharmacologic intervention.

PMID- 23953823
TI  - Tumor regression and sirolimus-based therapy in lung transplantation.

PMID- 23953824
TI  - Induction of carbonic anhydrase in SaOS-2 cells, exposed to bicarbonate and
      consequences for calcium phosphate crystal formation.
AB  - Ca-phosphate/hydroxyapatite crystals constitute the mineralic matrix of
      vertebrate bones, while Ca-carbonate dominates the inorganic matrix of otoliths.
      In addition, Ca-carbonate has been identified in lower percentage in apatite
      crystals. By using the human osteogenic SaOS-2 cells it could be shown that after
      exposure of the cells to Ca-bicarbonate in vitro, at concentrations between 1 and
      10 mm, a significant increase of Ca-deposit formation results. The crystallite
      nodules formed on the surfaces of SaOS-2 cells become denser and larger in the
      presence of bicarbonate if simultaneously added together with the mineralization
      activation cocktail (beta-glycerophosphate/ascorbic acid/dexamethasone). In
      parallel, with the increase of Ca-deposit formation, the expression of the
      carbonic anhydrase-II (CA-II) gene becomes upregulated. This effect, measured on
      transcriptional level is also substantiated by immunohistological studies. The
      stimulatory effect of bicarbonate on Ca-deposit formation is prevented if the
      carbonic anhydrase inhibitor acetazolamide is added to the cultures. Mapping the
      surface of the Ca-deposit producing SaOS-2 cells by scanning electron microscopy
      coupled with energy-dispersive X-ray analysis revealed an accumulation of the
      signals for the element carbon and, as expected, also for phosphorus. Finally, it
      is shown that ortho-phosphate and hydrolysis products of polyphosphate inhibit CA
      II activity, suggesting a feedback regulatory system between the CA-driven Ca
      carbonate deposition and a subsequent inactivation of this process by ortho
      phosphate. Based on the presented data we suggest that Ca-carbonate deposits act
      as bioseeds for a downstream Ca-phosphate deposition process. We propose that
      activators for CA, especially for CA-II, might be beneficial for the treatment of
      bone deficiency diseases. 

PMID- 23953826
TI  - The 18th World Congress on Disaster and Emergency Medicine.

PMID- 23953825
TI  - Stimulation of adipogenesis of adult adipose-derived stem cells using substrates
      that mimic the stiffness of adipose tissue.
AB  - Biochemical and biomechanical extracellular matrix (ECM) cues have recently been
      shown to play a role in stimulating stem cell differentiation towards several
      lineages, though how they combine to induce adipogenesis has been less well
      studied. The objective of this study was to recapitulate both the ECM composition
      and mechanical properties of adipose tissue in vitro to stimulate adipogenesis of
      human adipose-derived stem cells (ASCs) in the absence of exogenous adipogenic
      growth factors and small molecules. Adipose specific ECM biochemical cues have
      been previously shown to influence adipogenic differentiation; however, the
      ability of biomechanical cues to promote adipogenesis has been less defined.
      Decellularized human lipoaspirate was used to functionalize polyacrylamide gels
      of varying stiffness to allow the cells to interact with adipose-specific ECM
      components. Culturing ASCs on gels that mimicked the native stiffness of adipose
      tissue (2 kPa) significantly upregulated adipogenic markers, in the absence of
      exogenous adipogenic growth factors and small molecules. As substrate stiffness
      increased, the cells became more spread, lost their rounded morphology, and
      failed to upregulate adipogenic markers. Together these data imply that as with
      other lineages, mechanical cues are capable of regulating adipogenesis in ASCs. 

PMID- 23953827
TI  - A systematic, quantitative review of blood autoantibodies in schizophrenia.
AB  - OBJECTIVE: Schizophrenia is associated with immune system dysfunction, including
      an increased prevalence of autoimmune disorders and autoantibodies. We performed
      a systematic, quantitative review of self-reacting blood antibodies in patients
      with schizophrenia. METHOD: We identified articles by searching PubMed,
      PsychInfo, and ISI, and the reference lists of identified studies. RESULTS:
      Eighty-one of 111 studies identified met the inclusion criteria. There was a
      significant increased prevalence of positive titers for 20 different
      autoantibodies in patients with schizophrenia compared to controls. The
      prevalence of positive anti-cardiolipin IgG and NMDA receptor titers was also
      significantly increased in subjects with first-episode psychosis versus controls
      (p<0.01). Absolute titers for anti-cardiolipin IgG and IgM, and nerve growth
      factor were significantly increased in patients with schizophrenia compared to
      controls (p<0.02 for each). CONCLUSION: Schizophrenia is associated with an
      increased prevalence of multiple autoantibodies, although there is marked study
      heterogeneity, and correlations between autoantibodies and clinical features are
      inconsistent. This area merits more research evaluation, especially controlling
      for potential confounding factors such as clinical status, age, genetic
      background, psychotropic medications, BMI, and smoking.

PMID- 23953828
TI  - Association between cognitive insight and prefrontal function during a cognitive
      task in schizophrenia: a multichannel near-infrared spectroscopy study.
AB  - Insight has been studied mostly from a clinical perspective. Recently, the focus
      of this research field shifted to cognitive insight or the ability to monitor and
      correct the erroneous convictions of individuals. In this study, we investigated
      the relationship between cognitive insight and prefrontal function during a
      cognitive task in 30 patients with clinically stable schizophrenia and 30 age-
      and gender-matched healthy controls. We measured the changes in hemoglobin
      concentration in the prefrontal and temporal cortical regions during a verbal
      fluency task (VFT) by using 52-channel near-infrared spectroscopy (NIRS).
      Cognitive insight was measured using the Beck Cognitive Insight Scale (BCIS).
      Regional hemodynamic changes were significantly smaller in the schizophrenia
      group than in the control group in prefrontal and temporal regions, and
      significant positive relationship was observed between the score of the BCIS self
      reflectiveness subscale and right ventrolateral prefrontal and right temporal
      functions during the VFT. These results suggest that the right ventrolateral
      prefrontal and temporal cortical regions are associated with cognitive insight in
      clinically stable patients with schizophrenia and that NIRS is an efficient
      medical tool for monitoring these characteristics.

PMID- 23953830
TI  - Comparison of intravascular ultrasound with conventional venography for detection
      of extracranial venous abnormalities indicative of chronic cerebrospinal venous
      insufficiency.
AB  - PURPOSE: To investigate prevalence of extracranial abnormalities in azygos and
      internal jugular (IJ) veins using conventional venography and intravascular
      ultrasound (IVUS) in patients with multiple sclerosis (MS) being evaluated for
      chronic cerebrospinal venous insufficiency, a condition of vascular hemodynamic
      dysfunction. MATERIALS AND METHODS: PREMiSe (Prospective Randomized Endovascular
      therapy in Multiple Sclerosis) is a venous angioplasty study that enrolled 30
      patients with relapsing MS. The patients fulfilled two or more venous hemodynamic
      extracranial Doppler sonography screening criteria. Phase I of the study included
      10 patients and was planned to assess safety and standardize venography, IVUS,
      and angioplasty and blinding procedures; phase II enrolled 20 patients and
      further validated diagnostic assessments using the two invasive techniques.
      Venography was considered abnormal when >= 50% lumen-diameter restriction was
      detected. IVUS was considered abnormal when >= 50% lumen-diameter restriction,
      intraluminal defects, or reduced pulsatility was detected. RESULTS: No venography
      related or IVUS-related complications, including vessel rupture, thrombosis, or
      side effects of contrast media were recorded among the 30 study patients. IVUS
      detected venous abnormalities, including chronic, organized, thrombus-like
      inclusions were observed in 85% of azygos, 50% of right IJ, and 83.3% of left IJ
      veins, whereas venography demonstrated stenosis of >= 50% in 50% of azygos, 55%
      of right IJ, and 72% of left IJ veins. Sensitivity of venography for detecting
      IVUS abnormalities was 52.9%, 73.3%, and 80% for the azygos, left IJ, and right
      IJ veins, respectively. CONCLUSIONS: IVUS assessment of azygos and IJ veins
      showed a higher rate of venous abnormalities than venography. IVUS provides a
      diagnostic advantage over conventional venography in detecting extracranial
      venous abnormalities indicative of chronic cerebrospinal venous insufficiency.

PMID- 23953829
TI  - [Combined approach for the treatment of spontaneous temporal encephaloceles:
      transmastoid plus temporal minicraniotomy].
AB  - Spontaneous encephaloceles are defined as brain herniations with no apparent
      cause. The aim of this paper is to describe the surgical technique performed in
      our department. We reviewed the last 3 cases treated with combined approach
      (transmastoid plus minicraniotomy) with 2-layer closure. In all cases the bone
      defects were located and successfully sealed. We had no postoperative
      complications. There were no relapses in our follow-up period. The transmastoid
      approach has the advantage over the open approach with middle fossa craniotomy in
      that it locates the bone defect with no brain retraction. Nevertheless, it is not
      useful in large-sized, multiple or anterior defects. Due to those drawbacks, we
      think that the combined approach with temporal minicraniotomy is the best choice
      for this entity. 

PMID- 23953831
TI  - Haemostatic technique using a novel silicone gel dressing for tangential
      excisions in burn surgery.

PMID- 23953832
TI  - [Implementation of morbidity and mortality conferences in French intensive care
      units: a survey].
AB  - OBJECTIVE: A national survey was conducted by the "College francais d'anesthesie
      et de reanimation (CFAR)" and the "College des bonnes pratiques en reanimation
      (CBPR)", to analyze the implementation of morbidity and mortality conferences
      (MMCs) in French intensive care units (ICUs). STUDY DESIGN: An electronic
      questionnaire was set up. We directed the survey at French ICUs physicians
      registered in the two Colleges directories, only one form was filled in by each
      participating unit. RESULTS: From December 2009 to February 2010, Among the 170
      replies, 120 ICUs (71%) practiced MMC. No difference in the typology of the two
      groups was found. The median annual number of MMCs was 4 per year (1-15). The
      perimeter of the MMCs concerned only the ICU unit in 70 cases (58%), more than
      one ICU unit in the same department in 11 cases (9.8%), more than one department
      of ICU in 16 cases (13%) and other departments in 57 cases (48%). The events
      analyzed were: all deaths in 45 cases (37.5%), unexpected deaths in 50 cases
      (41.7%), severe adverse events in 67 cases (55.8%) and other events in 19 cases
      (15.8%). At least one adverse event defined by the two colleges in the process of
      "accreditation" was analyzed in 86 cases (72%). Participation of a physician of
      at least one other unit was reported in 56 cases (47%) and of medical students in
      62 cases (52%). The low rate of participation of ICU nurses was reported in 62
      cases (69.2%) and their absence in 35 cases (29%). MMCs consequences were
      drafting of new procedure in 99 cases (83%), changes in procedures in 75 cases
      (63%), conducting training programs in 60 cases (50%), organizational changes in
      86 cases (72%), adverse event declaration in 21 cases (18%) and monitoring
      indicators in 40 cases (33%). Among units which did not practice MMCs, Identified
      obstacles were organizational causes in 25 cases (50%), inexperience in seven
      cases (14%), lack of methodology in 4 cases (8%), realization of other methods of
      formative assessment in 4 cases (8%) and physician's refusal in three cases (6%).
      The fear of medico-legal problem was never reported as a barrier to MMCs
      practice. Forty-five units (90%) projected to practice MMR. CONCLUSION: This
      survey showed that the practice of MMR is common in French ICUs, allowing the
      identification of organizational problems, but also of training needs, joining
      one of the initial concerns that have led to their implementation. Expanding the
      participation to non-physician members of the units should be encouraged, without
      underestimating the difficulties particularly in the organizational domains that
      represent an obstacle to development of MMCs.

PMID- 23953833
TI  - [Is there need for a division operating theatre?].

PMID- 23953834
TI  - [Off-label use of recombinant factor VII (rFVIIa) in teaching hospitals in Paris
      in 2010].
AB  - INTRODUCTION: Recombinant activated factor VII (rFVIIa) (Novoseven((r))) was
      initially developed as a substitutive treatment in haemophiliacs but has then
      been used in situations of major haemorrhage in non-haemophiliacs (off-label
      use). The goal of the present study was to assess the practice patterns when
      rFVIIa is used in off-label indications in major teaching hospitals of Paris in
      2010. METHODS: We retrospectively identified files of patients in whom rFVIIa had
      been used. Physicians in charge of these patients (or the most proxy physician
      available) were contacted and files analysed with one of the authors. Quality of
      rFVIIa used in these off-label situations was determined based on either French
      or European guidelines or the available literature when no guidelines could be
      found. Three categories were defined for indication, dosage, timing, associated
      biological factors and overall use: adequate, acceptable (mainly adequate but
      lacking some characteristics of an "ideal" prescription) and inadequate (lacking
      most of the necessary characteristics of an "ideal" prescription). RESULTS: Among
      59 patients who had an off-label prescription of rFVIIa, 49 prescriptions could
      be analysed. Indication for use and timing of administration were adequate in
      100% of multiple trauma cases and 83% of obstetrical cases. Biological criteria
      associated with an improved efficacy were found in two thirds of prescriptions
      analysed. Overall, prescriptions were adequate or acceptable in 82% of cases.
      CONCLUSION: In the vast majority of patients who received rFVIIa for off-label
      indications in teaching hospitals of the Paris area in 2010, prescriptions were
      in line with recommendations.

PMID- 23953835
TI  - [Blood transfusion on battlefield. The Kabul hospital experience].
AB  - OBJECTIVES: Blood transfusion is an aspect of medical care on the battlefield.
      French assets include: red blood cell units (RBCu), lyophilized plasma (PLYO),
      fresh whole blood (FWB) but neither fresh-frozen plasma (FFP) nor platelets.
      French transfusion strategy in military operations follows the evolution of
      knowledge and resources. We describe the characteristics of the transfusion at
      the military hospital in Kabul. PATIENTS AND METHODS: Retrospective study of
      records of patients transfused between October 2010 to December 2011 conducted in
      Kabul from transfusion register. Variables studied were: patient characteristics,
      biology at admission, type and amount of transfusion products, evolution.
      RESULTS: One hundred and twenty-six patients were transfused: 49 military (39%)
      which 22 French soldier (17%), most of time afghan (n=97; 77%), mean age at 24
      years old (3-66). Two hundred and seventy-three RBCu from France were transfused
      and 350 unused were destroyed. Conditions leading to a transfusion were: 76 war
      wounds (60%), 21 trauma (17%) and 29 other (23%). In the first 24 hours, patients
      received in mean: two RBCu (0-12), one unit of FWB (0-18) and two PLYO (0-14).
      PLYO/RBCu ratio was 1/1.6. A massive transfusion (more than 10 RBCu) concerned 9%
      of patients. Twenty-seven percent of patients received FWB. We note 17 dead
      people (13.5%). CONCLUSION: The use of the FWB and PLYO in substitution of FFP
      and platelets can provide cares of high quality in a logistically constrained
      context while controlling costs.

PMID- 23953836
TI  - Study of agreement of aortic, radial and femoral blood pressures during aortic
      endografting.
AB  - PURPOSE: To estimate the agreement between radial or femoral, and ascending
      aortic invasive blood pressure values. PATIENTS AND METHODS: Prospective study on
      32 patients who underwent an aortic endografting under general anesthesia. After
      deploying the prosthesis under controlled hypotension, a catheter was introduced
      in the aorta to measure the staged systolic (SAP), diastolic (DAP) and mean (MAP)
      arterial pressures, in particular at the level of ascending aorta and femoral
      artery. RESULTS: No differences were observed between SAP, DAP or MAP measured in
      the aorta versus femoral or radial arteries. A better agreement was observed
      between the aortic and femoral MAP (bias of 1mmHg, limits of agreement between: 
      8.8mmHg and +10.8mmHg) than between the aortic and the radial MAP (bias of
      1.7mmHg, limits of agreement between: -14.1mmHg and +17.5mmHg). The comparison
      between radial and femoral MAP was not satisfying (bias of -4.7mmHg and limits of
      agreement between -19.1mmHg and +9.7mmHg). CONCLUSION: The femoral MAP is more
      accurate to predict value of the aortic MAP than the radial MAP in a hypotensive
      setting. The clinician should be aware of these discrepancies in conditions of
      hemodynamic impairment to optimize the treatment.

PMID- 23953837
TI  - LULL(ed) into complacency: a perspective on licenses and stem cell translational
      science.
AB  - The US has had a very successful model for facilitating the translation of a
      basic discovery to a commercial application. The success of the model has hinged
      on providing clarity on ownership of a discovery, facilitating the licensing
      process, providing adequate incentive to the inventors, and developing a self
      sustaining model for reinvestment. In recent years, technological, political, and
      regulatory changes have put strains on this model and in some cases have hindered
      progress rather than facilitated it. This is particularly true for the nascent
      field of regenerative medicine. To illustrate this, I will describe the
      contributing practices of several different entities, including universities,
      repositories, patent trolls, and service providers. It is my hope that the
      scientific community will be motivated to coordinate efforts against these
      obstacles to translation. 

PMID- 23953838
TI  - Membrane cut-off does not influence results regarding the measurement of small
      molecules - a comparative study between 20- and 100-kDa catheters in hepatic
      microdialysis.
AB  - BACKGROUND: Microdialysis is a method used to monitor hepatic tissue metabolism.
      Membranes with a molecular cut-off of 20 kilodalton (kDa) are currently used to
      measure the small metabolites glucose, glycerol, lactate and pyruvate. Using
      membranes with higher cut-off such as 100 kDa allows the possibility of measuring
      larger molecules but may affect results regarding small molecules. The aim was to
      compare microdialysis catheters with a cut-off of 20 and 100 kDa in the
      measurement of small molecules in a pig liver model. METHODS: Four microdialysis
      catheters were inserted into the liver of each pig used in the experiment (n =
      6). Two catheters with cut-off of 20 kDa were perfused with Ringer acetate, and
      two catheters with cut-off of 100 kDa: one perfused with Ringer acetate and one
      with hydroxyethyl starch (Voluven) at a flow rate of 0.3 MUl min(-1). Dialysate
      samples were collected at 40-min intervals and analysed for glucose, glycerol,
      lactate and pyruvate. RESULTS: Compared to the other catheters, the 100-kDa
      catheters perfused with Ringer acetate tended to measure higher dialysate
      concentrations of the small molecules, the difference reaching statistical
      significance in the case of pyruvate. Concentrations measured by the 100-kDa
      catheters perfused with Voluven were, however, comparable to the 20-kDa
      catheters. CONCLUSIONS: Microdialysis catheters with membrane cut-off of 20 and
      100 kDa can be used equally in hepatic microdialysis for the monitoring of
      glucose, glycerol, lactate and pyruvate, and lactate/pyruvate ratio if a high
      osmotic solution (Voluven) is used to perfuse the 100-kDa catheters.

PMID- 23953840
TI  - Spring-like fibers for cardiac tissue engineering.
AB  - Recapitulation of the cellular microenvironment of the heart, which promotes cell
      contraction, remains a key challenge in cardiac tissue engineering. We report
      here on our work, where for the first time, a 3-dimensional (3D) spring-like
      fiber scaffold was fabricated, successfully mimicking the coiled perimysial
      fibers of the heart. We hypothesized that since in vivo straightening and re
      coiling of these fibers allow stretching and contraction of the myocardium in the
      direction of the cardiomyocytes, such a scaffold can support the assembly of a
      functional cardiac tissue capable of generating a strong contraction force. In
      this study, the mechanical properties of both spring-like single fibers and 3D
      scaffolds composed of them were investigated. The measurements showed that they
      have increased elasticity and extensibility compared to corresponding straight
      fibers and straight fiber scaffolds. We have also shown that cardiac cells
      cultivated on single spring-like fibers formed cell-fiber interactions that
      induced fiber stretching in the direction of contraction. Moreover, cardiac cells
      engineered within 3D thick spring-like fiber scaffolds formed a functional tissue
      exhibiting significantly improved function, including stronger contraction force
      (p = 0.002), higher beating rate (p < 0.0001) and lower excitation threshold (p =
      0.02), compared to straight fiber scaffolds. Collectively, our results suggest
      that spring-like fibers can play a key role in contributing to the ex vivo
      formation of a contracting cardiac muscle tissue. We envision that cardiac
      tissues engineered within these spring-like fiber scaffolds can be used to
      improve heart function after infarction. 

PMID- 23953839
TI  - Bladder tissue regeneration using acellular bi-layer silk scaffolds in a large
      animal model of augmentation cystoplasty.
AB  - Acellular scaffolds derived from Bombyx mori silk fibroin were investigated for
      their ability to support functional tissue regeneration in a porcine model of
      augmentation cystoplasty. Two bi-layer matrix configurations were fabricated by
      solvent-casting/salt leaching either alone (Group 1) or in combination with silk
      film casting (Group 2) to yield porous foams buttressed by heterogeneous surface
      pore occlusions or homogenous silk films, respectively. Bladder augmentation was
      performed with each scaffold group (6 * 6 cm(2)) in juvenile Yorkshire swine for
      3 m of implantation. Augmented animals exhibited high rates of survival (Group 1:
      5/6, 83%; Group 2: 4/4, 100%) and voluntary voiding over the course of the study
      period. Urodynamic evaluations demonstrated mean increases in bladder capacity
      over pre-operative levels (Group 1: 277%; Group 2: 153%) which exceeded
      nonsurgical control gains (144%) encountered due to animal growth.In addition,
      animals augmented with both matrix configurations displayed increases in bladder
      compliance over pre-operative levels(Group 1: 357%; Group 2: 338%) similar to
      growth-related elevations observed in non-surgical controls (354%) [corrected].
      Gross tissue evaluations revealed that both matrix configurations supported
      extensive de novo tissue formation throughout the entire original implantation
      site which exhibited ultimate tensile strength similar to nonsurgical
      counterparts. Histological and immunohistochemical analyses showed that both
      implant groups promoted comparable extents of smooth muscle regeneration and
      contractile protein (alpha-smooth muscle actin and SM22alpha) expression within
      defect sites similar to controls. Parallel evaluations demonstrated the formation
      of a transitional, multi-layered urothelium with prominent cytokeratin,
      uroplakin, and p63 protein expression in both matrix groups. De novo innervation
      and vascularization processes were evident in all regenerated tissues indicated
      by synaptophysin-positive neuronal cells and vessels lined with CD31 expressing
      endothelial cells. Ex vivo organ bath studies demonstrated that regenerated
      tissues supported by both silk matrices displayed contractile responses to
      carbachol, alpha,beta-methylene-ATP, KCl, and electrical field stimulation
      similar to controls. Our data detail the ability of acellular silk scaffolds to
      support regeneration of innervated, vascularized smooth muscle and urothelial
      tissues within 3 m with structural, mechanical, and functional properties
      comparable to native tissue in a porcine model of bladder repair.

PMID- 23953842
TI  - Epidermal growth factor receptor targeting in cancer: a review of trends and
      strategies.
AB  - The epidermal growth factor receptor (EGFR) is a cell-surface receptor belonging
      to ErbB family of tyrosine kinase and it plays a vital role in the regulation of
      cell proliferation, survival and differentiation. However; EGFR is aberrantly
      activated by various mechanisms like receptor overexpression, mutation, ligand
      dependent receptor dimerization, ligand-independent activation and is associated
      with development of variety of tumors. Therefore, specific EGFR inhibition is one
      of the key targets for cancer therapy. Two major approaches have been developed
      and demonstrated benefits in clinical trials for targeting EGFR; monoclonal
      antibodies (mAbs) and tyrosine kinase inhibitors (TKIs). EGFR inhibitors like,
      cetuximab, panitumumab, etc. (mAbs) and gefitinib, erlotinib, lapatinib, etc.
      (TKIs) are now commercially available for treatment of variety of cancers.
      Recently, many other agents like peptides, nanobodies, affibodies and antisense
      oligonucleotide have also shown better efficacy in targeting and inhibiting EGFR.
      Now a days, efforts are being focused to identify molecular markers that can
      predict patients more likely to respond to anti-EGFR therapy; to find out
      combinatorial approaches with EGFR inhibitors and to bring new therapeutic agents
      with clinical efficacy. In this review we have outlined the role of EGFR in
      cancer, different types of EGFR inhibitors, preclinical and clinical status of
      EGFR inhibitors as well as summarized the recent efforts made in the field of
      molecular EGFR targeting. 

PMID- 23953841
TI  - The use of self-adjuvanting nanofiber vaccines to elicit high-affinity B cell
      responses to peptide antigens without inflammation.
AB  - Balancing immunogenicity with inflammation is a central tenet of vaccine design,
      especially for subunit vaccines that utilize traditional pro-inflammatory
      adjuvants. Here we report that by using a nanoparticulate peptide-based vaccine,
      immunogenicity and local inflammation could be decoupled. Self-assembled beta
      sheet-rich peptide nanofibers, previously shown to elicit potent antibody
      responses in mice, were found to be non-cytotoxic in vitro and, remarkably,
      elicited no measurable inflammation in vivo-with none of the swelling at the
      injection site, accumulation of inflammatory cells or cytokines, or production of
      allergic IgE that were elicited by an alum-adjuvanted vaccine. Nanofibers were
      internalized by dendritic cells and macrophages at the injection site, and only
      dendritic cells that acquired the material increased their expression of the
      activation markers CD80 and CD86. Immunization with epitope-bearing nanofibers
      elicited antigen-specific differentiation of T cells into T follicular helper
      cells and B cells into germinal center cells, as well as high-titer, high
      affinity IgG that cross-reacted with the native protein antigen and was
      neutralizing in an in vitro influenza hemagglutination inhibition assay. These
      responses were superior to those induced by alum and comparable to those induced
      by complete Freund's adjuvant. Thus, nanoparticulate assemblies may provide a new
      route to non-inflammatory immunotherapies and vaccines. 

PMID- 23953843
TI  - Novel dynamic measures of emetic behavior in musk shrews.
AB  - The emetic reflex occurs as a pattern of motor responses produced by a network of
      neurons in the hindbrain. Despite an understanding of the sequence of motor
      outputs that form an emetic episode (EE), the variability in the dynamics of
      multiple EEs across time remains a mystery. Many clinical investigations rely on
      once a day patient recall of total amount of vomiting, and preclinical studies
      frequently report only the total number of EE per unit time. The aim of the
      current study was to develop novel temporal measures of emetic activation in a
      preclinical model. Male and female musk shrews were tested with prototypical
      emetic stimuli: motion exposure (1 Hz), nicotine (5 mg/kg, sc), and copper
      sulfate (120 mg/kg, ig). New emetic measures included duration (time from first
      to last episode), rate, standard deviation of the inter-episode interval (SD-I),
      and a survival analysis of emetic latency (analyzed with Cox regression).
      Behavioral patterns associated with emesis were also assessed using statistical
      temporal pattern (T-pattern) analysis to measure nausea-like behaviors (e.g.,
      immobility). The emetic stimuli produced different levels of total EE number,
      duration, rate, and SD-I. A typical antiemetic, the neurokinin 1 receptor
      antagonist CP-99,994, suppressed the number of EEs but was less effective for
      reducing the duration or prolonging the emetic latency. Overall, the current
      study shows the use of novel dynamic behavioral measures to more comprehensively
      assess emesis and the impact of therapies.

PMID- 23953844
TI  - New type of hip arthroplasty failure related to modular femoral components:
      breakage at the neck-stem junction.
AB  - Total hip replacements (THR) with modular femoral components (stem-neck
      interface) make it possible to adapt to extramedullary femoral parameters
      (anteversion, offset, and length) theoretically improving muscle function and
      stability. Nevertheless, adding a new interface has its disadvantages: reduced
      mechanical resistance, fretting corrosion and material fatigue fracture. We
      report the case of a femoral stem fracture of the female part of the component
      where the modular morse taper of the neck is inserted. An extended trochanteric
      osteotomy was necessary during revision surgery because the femoral stump could
      not be grasped for extraction, so that a long stem had to be used. In this case,
      the patient had the usual risk factors for modular neck failure: he was an active
      overweight male patient with a long varus neck. This report shows that the female
      part of the stem of a small femoral component may also be at increased failure
      risk and should be added to the list of risk factors. To our knowledge, this is
      the first reported case of this type of failure. 

PMID- 23953845
TI  - Dietary patterns and functional disability in older Korean adults.
AB  - OBJECTIVES: This study examined the relationship between dietary patterns and
      disability in the Korean elderly. STUDY DESIGN: We used data from a cross
      sectional study of 327 men and 460 women aged >=65 years who completed the 2005
      Korea National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURES: A
      single 24-h dietary recall method was used to assess dietary intake and dietary
      patterns were identified by cluster analysis. Functional disability was assessed
      by the activities of daily living (ADL) and instrumental ADL (IADL) scales. The
      association of dietary patterns with ADL and IADL disability was analyzed by
      logistic regression adjusting for age, marital status, education, household
      income, region, chronic conditions, body mass index, smoking, alcohol drinking,
      physical activity, and energy intake. RESULTS: Two dietary patterns were
      identified in both men and women: the modified traditional dietary pattern,
      characterized by a relatively lower consumption of white rice, but higher
      consumption of fruits, dairy products, and legumes, and the traditional dietary
      pattern, characterized by high consumption of white rice. After controlling for
      covariates, in men, those who engaged in modified traditional dietary pattern,
      compared with traditional dietary pattern, showed a lower likelihood of ADL
      disability (odds ratio [OR]=0.17, 95% confidence interval [CI]: 0.05-0.56). In
      women, the modified traditional dietary pattern compared with the traditional
      pattern was associated with a significantly decreased risk of ADL (OR=0.45, 95%
      CI: 0.23-0.90) and IADL disability (OR=0.45, 95% CI: 0.28-0.72). CONCLUSIONS: The
      modified traditional dietary pattern is associated with a decreased risk of
      functional disability in older Korean adults.

PMID- 23953846
TI  - [Understanding logistic regression].
AB  - Logistic regression is one of the most common multivariate analysis models
      utilized in epidemiology. It allows the measurement of the association between
      the occurrence of an event (qualitative dependent variable) and factors
      susceptible to influence it (explicative variables). The choice of explicative
      variables that should be included in the logistic regression model is based on
      prior knowledge of the disease physiopathology and the statistical association
      between the variable and the event, as measured by the odds ratio. The main steps
      for the procedure, the conditions of application, and the essential tools for its
      interpretation are discussed concisely. We also discuss the importance of the
      choice of variables that must be included and retained in the regression model in
      order to avoid the omission of important confounding factors. Finally, by way of
      illustration, we provide an example from the literature, which should help the
      reader test his or her knowledge. 

PMID- 23953847
TI  - Highly stable carbon nanotube field emitters on small metal tips against
      electrical arcing.
AB  - Carbon nanotube (CNT) field emitters that exhibit extremely high stability
      against high-voltage arcing have been demonstrated. The CNT emitters were
      fabricated on a sharp copper tip substrate that produces a high electric field. A
      metal mixture composed of silver, copper, and indium micro- and nanoparticles was
      used as a binder to attach CNTs to the substrate. Due to the strong adhesion of
      the metal mixture, CNTs were not detached from the substrate even after many
      intense arcing events. Through electrical conditioning of the as-prepared CNT
      emitters, vertically standing CNTs with almost the same heights were formed on
      the substrate surface and most of loosely bound impurities were removed from the
      substrate. Consequently, no arcing was observed during the normal operation of
      the CNT emitters and the emission current remained constant even after
      intentionally inducing arcing at current densities up to 70 mA/cm2. 

PMID- 23953848
TI  - Attainment of normal lipid levels among high cardiovascular risk patients: pooled
      analysis of observational studies from the United Kingdom, Sweden, Spain and
      Canada.
AB  - BACKGROUND: Although low-density lipoprotein cholesterol (LDL-C) is the primary
      lipid target for cardiovascular disease (CVD) risk reduction, high-density
      lipoprotein cholesterol (HDL-C) and triglycerides (TG) have also emerged as risk
      factors. This study evaluated attainment of goal/normal lipid levels in current
      clinical practice among high-risk patients following lipid-modifying therapy
      (LMT). METHODS: Data for patients aged >=35years and on LMT for >=12months were
      identified from electronic medical records (United Kingdom and Sweden) and
      extracted from medical charts (Canada and Spain). High CVD risk was defined
      according to the Adult Treatment Panel III guidelines. An index period was
      defined, from January 1995-July 2008, during which patients received an initial
      LMT prescription. Prevalence of lipid abnormalities was assessed 12months before
      and after the index date. Multivariate logistic regressions evaluated predictors
      of attaining goal/normal lipid levels. RESULTS: Among 12,768 high-risk patients,
      75% had elevated LDL-C, 37% low HDL-C, and 30% elevated TG before LMT. Despite
      therapy (97% statins only), 23% had elevated LDL-C, 36% low HDL-C, 16% elevated
      TG, and 17% had >=2 abnormal lipid levels. Framingham risk score >20% (Odds
      Ratio, 95% confidence interval: 0.37,0.31-0.43), diabetes (0.75,0.64-0.88),
      hypertension (1.26,1.09-1.46), current smoker (0.82,0.70-0.95) and increased body
      mass index (0.95,0.94-0.96) were associated with the likelihood of attaining >=2
      normal lipid levels (vs. LDL-C goal only). CONCLUSION: Current approaches to
      lipid management improve LDL-C goal attainment; however, control of multiple
      lipid risk factors remains poor. Patients may benefit from more comprehensive
      approaches to lipid management, which treat multiple lipid abnormalities, as
      suggested in clinical guidelines.

PMID- 23953849
TI  - Awareness of hepatitis B virus reactivation among physicians authorized to
      prescribe chemotherapy.

PMID- 23953851
TI  - Acute brachial plexus neuropathy with involvement of cranial nerves IX, X, XI and
      XII.
AB  - INTRODUCTION: Acute brachial plexus neuropathy is characterized by acute onset of
      shoulder girdle and arm pain, followed by weakness of the shoulder and arm
      muscles. It affects primarily nerves of the upper trunk of the brachial plexus
      and the long thoracic nerve. Cranial nerve involvement is an infrequent
      association and implies a diagnostic challenge. We report a unique case of acute
      brachial plexus neuropathy with involvement of the cranial nerves IX, X, XI and
      XII. CASE REPORT: Fifty six year-old woman who developed acute dysphonia,
      dysphagia and left shoulder pain, followed, six days later, by left arm weakness.
      Needle examination showed only fibrillation potentials and positive sharp waves
      in the left deltoid muscle. MRI of the brachial plexus shows enlargement of the
      trunks, cords and terminal branches, with mild gadolinium enhancement.
      DISCUSSION: This case illustrates the unique presentation of neuralgic amyotrophy
      with involvement of nerves outside the brachial plexus, and the importance of MRI
      for diagnosis, in the absence of electrophysiologic involvement.

PMID- 23953850
TI  - Association of coffee consumption with all-cause and cardiovascular disease
      mortality.
AB  - OBJECTIVE: To evaluate the association between coffee consumption and mortality
      from all causes and from cardiovascular disease. PATIENTS AND METHODS: Data from
      the Aerobics Center Longitudinal Study representing 43,727 participants with
      699,632 person-years of follow-up were included. Baseline data were collected by
      an in-person interview on the basis of standardized questionnaires and a medical
      examination, including fasting blood chemistry analysis, anthropometry, blood
      pressure, electrocardiography, and a maximal graded exercise test, between
      February 3, 1971, and December 30, 2002. Cox regression analysis was used to
      quantify the association between coffee consumption and all-cause and cause
      specific mortality. RESULTS: During the 17-year median follow-up, 2512 deaths
      occurred (804 [32%] due to cardiovascular disease). In multivariate analyses,
      coffee intake was positively associated with all-cause mortality in men. Men who
      drank more than 28 cups of coffee per week had higher all-cause mortality (hazard
      ratio [HR], 1.21; 95% CI, 1.04-1.40). However, after stratification based on age,
      younger (<55 years old) men and women showed a significant association between
      high coffee consumption (>28 cups per week) and all-cause mortality after
      adjusting for potential confounders and fitness level (HR, 1.56; 95% CI, 1.30
      1.87 for men; and HR, 2.13; 95% CI, 1.26-3.59 for women). CONCLUSION: In this
      large cohort, a positive association between coffee consumption and all-cause
      mortality was observed in men and in men and women younger than 55 years. On the
      basis of these findings, it seems appropriate to suggest that younger people
      avoid heavy coffee consumption (ie, averaging >4 cups per day). However, this
      finding should be assessed in future studies of other populations.

PMID- 23953853
TI  - The association between TNF-alpha and insulin resistance in euglycemic women.
AB  - Chronic low levels of inflammation have links to obesity, diabetes and insulin
      resistance. We sought to assess the relationship between cytokine tumor necrosis
      factor (TNF-alpha) and insulin resistance in a healthy, euglycemic population.
      This is a prospective study of 574 non-diabetic mother and infant pairs. Maternal
      body mass index (BMI), TNF-alpha, glucose and insulin were measured in early
      pregnancy and at 28 weeks. Insulin resistance was calculated by HOMA index. At
      delivery birthweight was recorded and cord blood analysed for fetal C-peptide and
      TNF-alpha. In a multivariate model, maternal TNF-alpha in early pregnancy was
      predicted by maternal insulin resistance at the same time-point, (beta=0.54,
      p<0.01), and maternal TNF-alpha at 28 weeks was predicted by maternal insulin
      resistance in early pregnancy (beta=0.24, p<0.01) and at 28 weeks (beta=0.39,
      p<0.01). These results, in a large cohort of healthy, non-diabetic women have
      shown that insulin resistance, even at levels below those diagnostic of
      gestational diabetes, is associated with maternal and fetal inflammatory
      response. These findings have important implications for defining the pathways of
      fetal programming of later metabolic syndrome and childhood obesity.

PMID- 23953852
TI  - Genome-wide association studies of maximum number of drinks.
AB  - Maximum number of drinks (MaxDrinks) defined as "Maximum number of alcoholic
      drinks consumed in a 24-h period" is an intermediate phenotype that is closely
      related to alcohol dependence (AD). Family, twin and adoption studies have shown
      that the heritability of MaxDrinks is approximately 0.5. We conducted the first
      genome-wide association (GWA) study and meta-analysis of MaxDrinks as a
      continuous phenotype. 1059 individuals were from the Collaborative Study on the
      Genetics of Alcoholism (COGA) sample and 1628 individuals were from the Study of
      Addiction - Genetics and Environment (SAGE) sample. Family sample with 3137
      individuals was from the Australian twin-family study of alcohol use disorder
      (OZALC). Two population-based Caucasian samples (COGA and SAGE) with 1 million
      single-nucleotide polymorphisms (SNPs) were used for gene discovery and one
      family-based Caucasian sample was used for replication. Through meta-analysis we
      identified 162 SNPs associated with MaxDirnks (p < 10(-4)). The most significant
      association with MaxDrinks was observed with SNP rs11128951 (p = 4.27 * 10(-8))
      near SGOL1 gene at 3p24.3. Furthermore, several SNPs (rs17144687 near DTWD2,
      rs12108602 near NDST4, and rs2128158 in KCNB2) showed significant associations
      with MaxDrinks (p < 5 * 10(-7)) in the meta-analysis. Especially, 8 SNPs in DDC
      gene showed significant associations with MaxDrinks (p < 5 * 10(-7)) in the SAGE
      sample. Several flanking SNPs in above genes/regions were confirmed in the OZALC
      family sample. In conclusions, we identified several genes/regions associated
      with MaxDrinks. These findings can improve the understanding about the
      pathogenesis of alcohol consumption phenotypes and alcohol-related disorders.

PMID- 23953855
TI  - IL3 SNP rs40401 variant is a risk factor for rhinoconjunctivitis in Japanese
      women: the Kyushu Okinawa maternal and child health study.
AB  - BACKGROUND: No studies have investigated the relationship between IL3 single
      nucleotide polymorphism (SNP) rs40401 and allergic rhinitis. We performed a case
      control study to examine this issue and to assess interactions between the SNP
      and smoking or older siblings in young adult Japanese women. METHODS: Included
      were 393 women who met the criteria of the International Study of Asthma and
      Allergies in Childhood (ISAAC) for rhinoconjunctivitis. Controls were 767 women
      without rhinoconjunctivitis according to the ISAAC criteria who had not been
      diagnosed with allergic rhinitis by a doctor. RESULTS: Compared with women with
      the TT genotype of SNP rs40401, those with the CC genotype had a significantly
      increased risk of rhinoconjunctivitis: the adjusted OR was 1.52 (95% CI: 1.05
      2.19). This positive relationship was significant under the additive model: the
      adjusted OR was 1.23 (95% CI: 1.02-1.47). The positive association fell just
      short of the significance level under the dominant or recessive model. There was
      no significant interaction between SNP rs40401 and smoking with respect to
      rhinoconjunctivitis. Compared with subjects with the TT or TC genotype of IL3 SNP
      rs40401 who had one or more older siblings, those with the CC genotype who had no
      older siblings had a 2.33-fold increased risk of rhinoconjunctivitis;
      nevertheless, the interaction was not significant. CONCLUSION: This is the first
      study to show a significant positive association between IL3 SNP rs40401 variant
      and the risk of rhinoconjunctivitis. We could not find evidence for interactions
      between SNP rs40401 and smoking or older siblings affecting rhinoconjunctivitis.

PMID- 23953854
TI  - Lymphocyte-mediated macrophage apoptosis during IL-12 stimulation.
AB  - In contrast to the well known immunostimulatory roles of IL-12, little has been
      known about its immunosuppressive roles. In the present study, IL-12-activated
      lymphocyte-mediated macrophage apoptosis was investigated by employing murine
      lymphocyte/macrophage cocultures. IL-12-activated lymphocytes and their culture
      supernatants induced an inducible nitric oxide synthase (iNOS)-mediated nitric
      oxide (NO) synthesis in macrophages. The NO synthesis was markedly inhibited by
      blocking antibodies to IFN-gamma and TNF-alpha, suggesting the key role of these
      lymphocyte cytokines in mediating the NO synthesis. The endogenously produced NO
      inhibited macrophage proliferation, and induced apoptosis in concordance with the
      accumulation of p53, phosphatase and tensin homologue deleted on chromosome 10
      (PTEN) and DR5, and the activation of caspase-3, processes that were inhibited by
      N(G)-monomethyl-l-arginine, aminoguanidine (NO synthase inhibitors) and 2-(4
      carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (an NO scavenger).
      These results were further supported by the findings obtained from the
      experiments employing IFN-gamma-knockout and iNOS-knockout mice. Our study
      demonstrated a novel, non-contact-dependent mechanism of macrophage suppression
      by IL-12-activated lymphocytes: induction of growth inhibition and apoptosis of
      macrophages due to endogenous NO synthesis induced by cytokines secreted from IL
      12-activated lymphocytes.

PMID- 23953857
TI  - From the editor's perspective....

PMID- 23953856
TI  - CXCL1 expression in human decidua in vitro is mediated via the MAPK signalling
      cascade.
AB  - Early molecular interaction between embryo and mother, involving
      chemoattractants, especially chemokine CXC-motif ligand 1 (CXCL1)(2), determines
      the pregnancy outcome. So far nothing is known about the signalling cascades of
      CXCL1 expression in human decidua. The aim of the study was to identify
      signalling cascades mediating the CXCL1 expression in human decidua incubated
      with IL-1beta as a major secretion product of the embryo. Therefore, decidualised
      endometrial stromal cells were incubated with IL-1beta in a concentration- and
      time-dependent manner. The specificity of the IL-1beta induced CXCL1 expression
      was verified by application of the IL-1 receptor antagonist, which opposed the
      binding of IL-1beta to its receptor, leading to a dose dependent diminished to
      complete CXCL1 elimination. IL-1beta signalling was investigated using inhibitors
      for MAPK, STAT3 and JNKinase cascades. The CXCL1 secretion of decidualised
      endometrial cells was measured by ELISA. The MAPK signalling cascade was explored
      by western blot analysis of ERK and NFkappaB p65(3) as well as phospho ERK and
      pp65 activation by IL-1beta in detail. A statistical significant increase in
      CXCL1 mRNA- and protein-expression after incubation with 0.1ng/ml IL-1beta after
      48h was detected. CXCL1 protein secretion could be completely prevented by IL-1
      receptor antagonist treatment. Only inhibition of the MAPKinase pathway resulted
      in a statistically significant decrease of CXCL1 protein secretion. Initiation of
      the MAPK pathway depicted by phospho ERK activation started as early as 2min
      after coincubation of decidualised endometrial stromal cells with IL-1beta.
      Activation of NFkappaB p65 could be measured within 15min of IL-1beta incubation
      in decidualised endometrial stromal cells. CXCL1 is a target for the embryos'
      secretion product IL-1beta in decidualised endometrial stromal cells during the
      peri-implantation period. IL-1beta's rapid effect on CXCL1 synthesis is uniquely
      mediated via the MAPK-signalling cascade and the activation of CXCL1s'
      transcription factor NFkappaB p65.

PMID- 23953859
TI  - Management for the case of twice ruptured anterior communicating artery aneurysm:
      from nursing perspective.
AB  - The anterior communicating artery (ACoA) is the most common site of cerebral
      aneurysms, accounting for as much as 36% of aneurysms. Microsurgical clipping and
      coil embolization are treatment modalities for ruptured and nonruptured cerebral
      aneurysms. Compared with surgical clipping, coil embolization has a relatively
      lower mortality and incidence of cognitive impairment in patients. However,
      successful management of the patient with twice ruptured ACoA aneurysm is facing
      critical challenges.This article has described a case of twice ruptured aneurysm
      with the first rupture occurring when the patient was admitted and the second
      rupture occurring during coil embolization. Perioperative nursing assessment,
      monitoring, intervention, patient teaching, and the nurse's role are discussed
      from a nursing perspective.

PMID- 23953858
TI  - Intraoperative stress and anxiety reduction with music therapy: a controlled
      randomized clinical trial of efficacy and safety.
AB  - OBJECTIVE: The purpose of this study was to investigate the music therapy (MT)
      effect in levels of intraoperative anxiety in patients undergoing crossectomy
      with stripping of the great saphenous vein and to assess the efficacy, safety,
      and feasibility of this alternative therapy as a complement of standard
      intraoperative care. MATERIAL AND METHODS: The study is a simple blind,
      controlled, parallel groups, prospective randomized clinical trial. Patients were
      allocated by means of randomized controlled sampling. The study was performed in
      the surgery room of Getafe University Hospital in Madrid. The study was carried
      out in 40 patients, 20 randomized to the experimental group and 20 randomized to
      the control group, with an age range from 27 to 70 years. The control group was
      given intraoperative routine attention, and the experimental group was given an
      MT passive intervention that consisted of audition of musical fragments during
      varicose veins surgery. These pieces previously showed relaxing actions on the
      cardiovascular system. The anxiety levels were measured by means of pre- and
      postsurgical questionnaires by a blinded investigator for the study arm to which
      the patients had been randomized. Heart rate and systolic and diastolic blood
      pressures were determined during the intervention, and adrenaline and
      noradrenaline plasma levels were determined before and after the surgical
      procedure. RESULTS: The majority of the patients in the MT group (95%) and
      standard care group (90%) completed the study. There were no statistical
      differences between the control and experimental groups in heart rate gradient or
      systolic and diastolic blood pressures measured after the intervention. The
      anxiety state and the stress feeling scale score after surgery were significantly
      inferior in the MT group (94.7% vs 57.9% decrease in anxiety levels, P < .05, and
      stress score of 1.31 vs 2.36, P < .05, respectively). The adverse events ratio
      was low and occurred with similar frequency in both groups. CONCLUSIONS: The MT
      intervention was easily implemented in the context of nursing care received
      during varicose vein surgery and was positively accepted and valued by the
      majority of the patients. MT is a safe procedure that is proved to reduce anxiety
      and stress in the study patients.

PMID- 23953860
TI  - A review of patients with renal disease undergoing vascular access surgery: is
      gray-scale ultrasound enough?
AB  - BACKGROUND: An adequate fistula or graft is essential to long-term survival and
      quality of life for patients with end-stage renal disease (ESRD) who are
      receiving hemodialysis because of its lower complication rates, lower costs, and
      prolonged patency. Use of duplex ultrasound for preoperative planning is
      currently recommended by the Kidney Disease Outcomes Quality Initiative for
      patients with ESRD with prior fistulas or grafts, central lines, pacemakers, and
      prior chest or arm surgery. The preoperative evaluation consisted of gray-scale
      ultrasound and physical examination in all patients with ESRD in this study. The
      current study determined the baseline data, including the type of vascular
      access, functional patency of access, associated morbidity, and preoperative
      demographics and comorbidities, including prior dialysis access. The primary
      objective was to determine the frequency of revision surgery, to identify the
      potential cases that may indicate the need for better assessments (eg, duplex
      ultrasound), and to improve fistula and graft success rates. MATERIALS AND
      METHODS: A retrospective chart review of patients with ESRD who underwent native
      fistula or graft access creation in a 13-month time period from 2010 to 2011 was
      completed. Seventy-six surgical procedures were performed on 53 subjects.
      Included variables were age, race, gender, smoking status, body mass index, stage
      of chronic kidney disease at referral, previous central lines/pacemakers,
      fistulas, or grafts. Comorbidities identified included diabetes mellitus (DM),
      hypertension (HTN), and coronary artery disease (CAD). The types of access,
      location, maturation, infection, failure, or revision were noted. Continuous
      variables are shown in frequencies and mean. Categoric data were compared using
      chi-square analysis. RESULTS: During the 13-month study period, 76 surgical
      procedures were performed in 53 patients, with 39.6% of patients undergoing
      multiple surgical procedures. The majority of patients were male (98%) and white
      (58.5%), with a history of HTN (96.2%) and DM (64.2%). The mean age was 68 years,
      with most patients presenting in stage 5 chronic kidney disease (92.5%). Some
      67.9% of patients had prior central lines or pacemakers; of those, 56.6% had
      previous fistulas or grafts. Negative significance was determined between the
      comorbidities DM/HTN/CAD alone or grouped as a cohort and multiple surgeries.
      Positive significance was found between multiple surgical procedures and those
      with prior access/pacemaker/central line (chi-square [1, N = 53] = exact P =
      .04). CONCLUSIONS: Patients with ESRD undergoing access creation presenting with
      prior central lines, pacemakers, or arm surgery (fistulas or grafts) were more
      likely to undergo multiple surgeries to obtain a functional graft or fistula for
      hemodialysis use than those patients with ESRD without prior central lines,
      pacemakers, or arm surgery (fistulas or grafts). Color duplex ultrasound should
      be considered as a standard for preoperative assessment in an effort to improve
      fistula or graft success rates.

PMID- 23953861
TI  - An integrative review: application of self-efficacy instruments for walking in
      populations with peripheral arterial disease.
AB  - OBJECTIVE: The study objective was to identify which self-efficacy measurement
      instruments are being used for walking in patients with peripheral arterial
      disease (PAD), the psychometrics of these instruments, and recommendations for
      use in research on patients with PAD. BACKGROUND: PAD is a common problem for
      individuals with similar risk factors as cardiovascular disease (CVD). Experts
      recommend a supervised walking program with incremental increases in speed and
      distance as an initial treatment for patients with intermittent claudication.
      Because patients may experience pain while walking, there is a tendency to be
      nonadherent with exercise therapy, and many limit or avoid walking all together,
      resulting in a sedentary lifestyle. Self-efficacy plays a role in determining a
      person's confidence in his or her ability to participate in an exercise program.
      Data sources for this study were PubMed, Cumulative Index of Nursing and Allied
      Health Literature, PsycINFO, and the Cochrane database. METHODS: The integrative
      review method described by Wittemore and Knafl was used for this review
      (Wittemore R, Knafl K. The integrative review: updated methodology. J Adv Nurs
      2005;52:546-53.). Publications were retrieved electronically and reviewed for
      inclusion on the basis of studies that measured self-efficacy for walking in
      populations with PAD, peripheral vascular disease, and CVD. The analysis
      consisted of 9 publications. RESULTS: Only 2 studies were specific to the
      population with PAD. The remaining studies addressed self-efficacy issues in CVD
      or congestive heart failure. The analysis identified 4 instruments based on
      Bandura's Social Cognitive Theory that were used to assess self-efficacy: (1) the
      Self-Efficacy Expectation Scale, (2) the Self-Efficacy for Managing Chronic
      Disease Scale, (3) the Performance-Based Efficacy Scale, and (4) the Barriers
      Self-Efficacy Scale. The Self-Efficacy Expectation Scale was most frequently used
      in these studies. CONCLUSIONS: The use of the Self-Efficacy Expectation Scale
      instruments for walking in patients with PAD is limited because reliability and
      validity have been demonstrated in an older, mostly white population with CVD and
      congestive heart failure. Instruments that encompass the key constructs of self
      efficacy, including physical, personal, and environmental aspects, would allow
      full evaluation with identification of potential explanations for success or
      failure for the chosen outcome. This should be taken into consideration in future
      studies when using instruments of self-efficacy.

PMID- 23953862
TI  - Review of article: Prevalence of obesity and trends in the distribution of body
      mass index among US adults, 1999-2010 by Katherine M. Flegal, PhD; Margaret D.
      Carroll, MSPH; Brian K. Kit, MD; Cynthia L. Ogden, PhD (JAMA 2012;307:491-7).

PMID- 23953863
TI  - The chrondroitin sulfate proteoglycan (CSPG4) regulates human trophoblast
      function.
AB  - INTRODUCTION: Trophoblast growth and invasion of the uterine endometrium are
      critical events during placentation and are tightly regulated by locally produced
      factors. Abnormal placentation can result in early miscarriage or preeclampsia
      and intrauterine growth restriction, leading to impaired fetal and/or maternal
      health. Chondroitin sulfate proteoglycan 4 (CSPG4) is involved in cancer cell
      migration and invasion, processes which are critical during placentation but
      unlike in cancer, trophoblast invasion is highly regulated. CSPG4 expression and
      function in trophoblast is unknown. We determined CSPG4 expression in human first
      trimester placenta and implantation sites, and investigated whether CSPG4
      influenced proliferation, migration and invasion of a human extravillous
      trophoblast (EVT) cell line (HTR8/SVneo cells) as a model for extravillous
      trophoblast (EVT). METHODS AND RESULTS: Immunoreactive CSPG4 localized to EVT
      cells in the trophoblast shell, subpopulations of interstitial EVT cells within
      the decidua and cytotrophoblast cells in placental villi. In HTR8/SVneo cells,
      siRNA knockdown of CSPG4 stimulated proliferation and decreased
      migration/invasion. In primary first trimester placental villi explants two
      cytokines, interleukin 11 (IL11) and leukemia inhibitory factor (LIF) with known
      roles in trophoblast function, stimulated CSPG4 mRNA expression and
      immunoreactive protein in the cyotrophoblast. DISCUSSION AND CONCLUSION: This is
      the first demonstration of the production and function of CSPG4 in human
      placentation. These data suggest that locally produced CSPG4 stimulates human EVT
      migration and invasion and suggests that IL11 and LIF regulate villous
      cytotrophoblast differentiation towards the invasive phenotype at least in part
      via CSPG4.

PMID- 23953864
TI  - Expression profiling of autophagy associated genes in placentas of preeclampsia.
AB  - Autophagy, a mechanism of cell survival during times of stress, may be active in
      normal placental maintenance, cushioning the fetus from strain during
      fluctuations in nutrient availability. Moreover, in cases of placental
      insufficiency, often present in preeclampsia, autophagy may be defective. We used
      published microarray datasets to analyze differential expression of autophagy
      pathway genes. No statistically significant difference in autophagy associated
      gene expression was found in preeclamptic vs. normal placenta samples. Thus
      although preeclampsia displays many of the features suggestive of altered
      autophagy, impaired placental autophagy as a cause of preeclampsia is not
      supported by whole placental tissue differential expression profiling.

PMID- 23953865
TI  - Thrombin weakens the amnion extracellular matrix (ECM) directly rather than
      through protease activated receptors.
AB  - INTRODUCTION: Preterm premature rupture of fetal membranes (pPROM) is a major
      cause of preterm birth. Abruption associated thrombin production, and infection
      inflammation associated cytokine production reportedly play major roles in pPROM.
      Utilizing an in vitro model-system we have confirmed that both thrombin and
      inflammatory cytokines remodel and biomechanically weaken amnion, the load
      bearing component of FM. Also, we have shown thrombin directly weakens isolated
      amnion but cytokines weaken amnion only indirectly by initially interacting with
      choriodecidua and releasing unidentified soluble activator(s). This study's
      purpose was to determine whether thrombin weakens the isolated amnion through
      thrombin receptor-protease activated receptors (PARs 1,2,3,4), activation of
      previously secreted extracellular matrix (ECM) enzymes, or by direct action on
      the ECM. METHODS: Primary amnion cells and isolated amnion were tested for PARs
      by immunohistochemistry, Western Blot and rtPCR. Cell-free amnion ECM was
      produced by devitalizing isolated amnion by exposure to UV light and subsequent
      freeze-thaw cycles. Devitalized amnion membrane explants were incubated with
      thrombin and biomechanically tested. RESULTS: PARs were not found in amnion or
      amnion cells. Thrombin induced dose-dependent weakening of devitalized amnion
      explants. Preincubation with the thrombin inhibitor hirudin prevented thrombin
      induced weakening. Thrombin converted pro-MMP2 embedded in the devitalized amnion
      ECM to multiple active forms. Thrombin also directly digested gelatin gels in
      zymograms suggesting the possibility of direct degradation of amnion ECM
      components. DISCUSSION: Thrombin appears to directly weaken the amnion ECM and
      additionally activates stored pro-MMP2 to active forms that may further enhance
      amnion ECM degradation. CONCLUSION: Thrombin weakens amnion directly rather than
      through PARs.

PMID- 23953866
TI  - Identification of biomarkers for preterm delivery in mid-trimester amniotic
      fluid.
AB  - OBJECTIVE: We investigated whether the level of vascular endothelial growth
      factor (VEGF) and inflammatory markers in mid-trimester amniotic fluid have
      predictive value for spontaneous preterm birth in singleton pregnancy. METHOD:
      Our subjects were 72 pregnant women who were undertaken with amniocentesis from
      16 to 19 weeks of gestation. 36 cases were women with preterm delivery, and other
      36 cases were matched women with full-term delivery. Stored amniotic fluid was
      investigated after the delivery. The levels of matrix metalloproteinases-8 (MMP
      8), interleukin-6 (IL-6), C-reactive protein (CRP), and VEGF were measured by
      enzyme-linked immunosorbent assay (ELISA) and Western blot. RESULTS: The levels
      of MMP-8 and IL-6 in preterm group were significantly higher than control group
      (5.76 +/- 1.53 ng/ml vs 4.89 +/- 1.77 ng/ml and 170.54 +/- 55.69 pg/ml vs 141.92
      +/- 57.21 pg/ml, respectively) (p < 0.05). In terms of VEGF, the levels were
      elevated in preterm group (30.76 +/- 4.06 pg/ml vs 22.36 +/- 7.03 pg/ml) (p <
      0.05). CONCLUSION: This study suggests that elevated levels of IL-6 and MMP-8 in
      amniotic fluid at mid-trimester are predictive of preterm delivery, and that VEGF
      which is representative of angiogenesis can be a new and useful predictor of
      preterm delivery.

PMID- 23953867
TI  - Bowel and bladder-control anxiety: a preliminary description of a viscerally
      centred phobic syndrome.
AB  - BACKGROUND: People with anxiety disorders occasionally report fears about losing
      control of basic bodily functions in public. These anxieties often occur in the
      absence of physical disorder and have previously been recognized as "obsessive"
      anxieties reflecting a preoccupation with loss of bowel/bladder control.
      Motivated by our observations of the non-trivial occurrence of such anxieties in
      our clinical practice we sought to fill a gap in the current understanding of
      "bowel/bladder-control anxieties". METHOD: Eligible participants completed an
      internet survey. RESULTS: Bowel/bladder-control anxieties (n = 140) tended to
      emerge in the mid to late 20s and were associated with high levels of avoidance
      and functional impairment. There was a high prevalence of panic attacks (78%);
      these were especially prevalent among those with bowel-control anxiety. Of those
      with panic attacks, 62% indicated that their main concern was being incontinent
      during a panic attack. Significantly, a proportion of respondents (~16%) reported
      actually being incontinent during a panic attack. Seventy percent of participants
      reported intrusive imagery related to loss of bowel/bladder control. Intrusion
      related distress was correlated with agoraphobic avoidance and general role
      impairment. Some differences were noted between those with predominantly bowel-,
      predominantly bladder- and those with both bowel and bladder-control anxieties.
      CONCLUSION: This preliminary characterization indicates that even in a non
      treatment seeking community sample, bowel/bladder-control anxieties are
      associated with high levels of distress and impairment. Further careful
      characterization of these anxieties will clarify their phenomenology and help us
      develop or modify treatment protocols in a way that takes account of any special
      characteristics of such viscerally-centred phobic syndromes.

PMID- 23953868
TI  - Methemoglobinemia: a review and recommendations for management.

PMID- 23953869
TI  - Preoperative mild cognitive dysfunction predicts pulmonary complications after
      coronary artery bypass graft surgery.
AB  - OBJECTIVES: In elderly patients with mild cognitive impairment, noncompliance
      with respiratory exercises, ineffective expectoration, reluctance in
      mobilization, and difficulty in learning the use of drugs such as inhalers were
      observed in the early postoperative period after coronary artery bypass graft
      surgery. It was hypothesized that respiratory complications may be more frequent
      in these patients, and so the postoperative respiratory complications in patients
      with preoperative mild cognitive impairment were compared with the postoperative
      respiratory complications of a control group. DESIGN: A prospective cohort
      control. SETTING: A university hospital. PARTICIPANTS: Patients undergoing
      elective coronary artery bypass graft surgery. INTERVENTIONS: Investigators
      separated 48 patients>70 years old who were scheduled for elective coronary
      artery bypass graft surgery into two groups: patients with preoperative mild
      cognitive impairment (group A, n = 25) and patients with no cognitive impairment
      (control group; group B, n = 23). The patients' cognitive status was evaluated
      preoperatively by the Montreal Cognitive Assessment test. MEASUREMENTS AND MAIN
      RESULTS: Pulmonary functions and respiratory complications were evaluated via
      chest x-rays and spirometry tests preoperatively and postoperatively. A
      significant difference was observed between the groups, particularly with regard
      to atelectasis and prolonged ventilation (p<0.001 and p<0.05). No significant
      impairment was observed in the spirometry tests of the control group. However, a
      significant deterioration was observed in the postoperative spirometry tests of
      patients with preoperative mild cognitive impairment. CONCLUSIONS: This study
      suggested that mild cognitive impairment was associated with pulmonary
      complications after coronary artery bypass graft surgery.

PMID- 23953870
TI  - [Echocardiography for fetuses and children: what's new?].

PMID- 23953871
TI  - [Chronic pain and regional anesthesia in children].
AB  - Chronic pain is usually underestimated in children, due to lack of knowledge and
      its specific signs. In addition to suffering, chronic pain causes a physical,
      psychological, emotional, social, and financial burden for the child and his
      family. Practitioners may find themselves in a situation of failure with
      depletion of medical resources. Some types of chronic pain are refractory to
      conventional systemic treatment and may require the use of regional anesthesia.
      Cancer pain is common in children and its medical management is sometimes
      insufficient. It is accessible to neuroaxial or peripheral techniques of regional
      anesthesia if it is limited to an area accessible to one of these techniques and
      no contraindications (e.g., thrombopenia) are present. Complex regional pain
      syndrome 1 is not rare in children and adolescents, but it often goes
      undiagnosed. Regional anesthesia may contribute to the treatment of complex
      regional pain syndrome 1, mainly in case of recurrence, because it provides rapid
      effective analgesia and allows rapid implementation of intensive physiotherapy.
      These techniques have also shown interest in phantom limb pain after limb
      amputation, but they remain controversial for erythromelalgia pain or chronic
      abdominopelvic pain. Finally, the treatment of postdural puncture headache due to
      cerebrospinal fluid leak can be treated by performing an epidural injection of
      the patient's blood, called a blood-patch. Finally, the management of children
      with chronic pain should be multidisciplinary (pediatrician, physiotherapist,
      psychologist, surgeon, anesthesiologist) to support the child and her problem in
      its entirety. 

PMID- 23953872
TI  - [Evaluation of peripherally inserted central catheters in a pediatric
      population].
AB  - A peripherally inserted central catheter (PICC) is a central venous access mostly
      used in France in the adult population, whereas it is only rarely used in the
      pediatric population. The main objective of this study was to analyze a cohort of
      children treated with PICCs inserted under radiological guidance. We conducted a
      single-center study in the Radiology department of Nice University Hospital and
      the Lenval Foundation Children's Hospital. During a 43-month period between
      November 2008 and June 2012, a total of 67 catheter placement attempts were
      performed in 57 pediatric patients aged from 7 months to 18 years. We achieved
      95.5% technical success with a median procedure duration of 17min. Only 6% of the
      PICC placements required light intravenous sedation; all the others were
      performed using a combination of local anesthesia, EMLA cream, and equimolar
      mixture of oxygen and nitrous oxide (EMONO). Subjective scale analysis of pain
      during catheter insertion showed a median score of 2.1. Catheter life ranged from
      1 to 210 days (median, 38.3 days) with the treatment fully completed in 75% of
      the cases. The overall complication rate was 18.7% (4.9 per 1000 catheter-days),
      largely dominated by mechanical complications (9.4%) such as accidental removal
      (6.2%) or catheter obstruction (3.1%). Infectious complications occurred in 7.8%
      of the patients. The duration of catheterization and the use of tape to secure
      the catheter significantly affected the occurrence of complications. Peripheral
      insertion of central catheters was highly feasible in infants and children. It is
      a simple, safe, and effective alternative to intravenous central devices in the
      pediatric population. The occurrence of complications, typically mechanical, must
      be reduced and prevented by strict management of this type of central line by the
      nursing team. 

PMID- 23953873
TI  - Hiking in suicidal patients: neutral effects on markers of suicidality.
AB  - BACKGROUND: Regular physical activity promotes physical and mental health.
      Psychiatric patients are prone to a sedentary lifestyle, and accumulating
      evidence has identified physical activity as a supplemental treatment option.
      METHODS: This prospective, randomized, crossover study evaluated the effects of
      hiking in high-risk suicidal patients (n = 20) who performed 9 weeks of hiking (2
      3 hikes/week, 2-2.5 hours each) and a 9-week control period. RESULTS: All
      patients participated in the required 2 hikes per week and thus showed a
      compliance of 100%. Regular hiking led to significant improvement in maximal
      exercise capacity (hiking period Delta: +18.82 +/- 0.99 watt, P < .001; control
      period: P = .134) and in aerobic capability at 70% of the individual heart rate
      reserve (hiking period Delta: +8.47 +/- 2.22 watt; P = .010; control period: P =
      .183). Cytokines, associated previously with suicidality (tumor necrosis factor
      alpha, interleukin-6, S100), remained essentially unchanged. CONCLUSIONS: Hiking
      is an effective and safe form of exercise training even in high-risk suicidal
      patients. It leads to a significant improvement in maximal exercise capacity and
      aerobic capability without concomitant deterioration of markers of suicidality.
      Offering this popular mode of exercise to these patients might help them to adopt
      a physically more active lifestyle.

PMID- 23953874
TI  - Acute aortic dissection in blacks: insights from the International Registry of
      Acute Aortic Dissection.
AB  - BACKGROUND: Few data exist on race-related differences in acute aortic dissection
      patients. METHODS: We evaluated black (n = 189, 14%) or white (n = 1165, 86%)
      patients (mean age 62.8 +/- 15.3 years; 36.4% women) enrolled in 13 US centers
      participating in the International Registry of Acute Aortic Dissection. We
      excluded patients of other racial descent. RESULTS: Type B acute aortic
      dissection was more frequent in the black cohort (52.4% vs 39.3%, P = .001).
      Black patients were younger (mean age 54.6 +/- 12.8 years vs 64.2 +/- 15.2 years,
      P <.001) and more likely to have a history of cocaine abuse (12% vs 1.6%, P
      <.001), hypertension (89.7% vs 73.9%, P <.001), and diabetes (13.2% vs 6.4%, P =
      .001). Conversely, they were less likely to have bicuspid aortic valve (1.8% vs
      5.8%, P = .029), iatrogenic dissection (0.5% vs 4.5%, P = .010), and prior aortic
      dissection repair (7.7% vs 12.8%, P = .047). Presenting features were similar
      except for more abdominal pain (44.6% vs 30.6%, P <.001) and left ventricular
      hypertrophy on echocardiogram (44.2% vs 20.1%, P <.001) in blacks. Management was
      similar. Hypotension/shock/tamponade was less common (7.6% vs 20.1%, P <.001),
      whereas acute kidney failure was more common (41.0% vs 21.7%, P <.001) in blacks.
      Mortality was similar in-hospital (14.3% vs 19.1%, P = .110, odds ratio 0.704,
      95% confidence interval 0.457-1.085) and at 3 years postdischarge, as evaluated
      by Kaplan-Meier survival analysis (22.0% vs 14.3%, P = .224, SE = 0.062 and
      0.018). CONCLUSIONS: Our study shows differences in type, etiology, and
      presentation of blacks and whites with acute aortic dissection, yet similar
      mortality for these cohorts.

PMID- 23953875
TI  - Pocket-sized, hand-carried ultrasound: the value of 'eating at home'.

PMID- 23953876
TI  - The overuse of serum ceruloplasmin measurement.
AB  - BACKGROUND: Wilson disease is rare, found in 3 of 100,000 people (0.03%).
      Ceruloplasmin is often ordered to evaluate liver enzyme elevations. Because
      Wilson disease often presents before middle-age, the American Association for the
      Study of Liver Disease recommends screening patients between the ages of 3 and 55
      years with liver abnormalities of uncertain cause. We evaluate guideline
      adherence and the clinical and economic impact of current clinical use of
      ceruloplasmin. METHODS: We reviewed all ceruloplasmin measurements at a clinical
      laboratory that serves a large primary care network, specialty clinics, and a 600
      bed tertiary referral center between January 1, 2003, and December 12, 2011.
      RESULTS: Ceruloplasmin was measured 5325 times in 5023 unique patients, resulting
      in 8 (0.16%) new Wilson disease diagnoses. Ceruloplasmin's positive predictive
      value was 8.4% (95% confidence interval, 7.7-9.3) and false-positive rate was
      98.1% (95% confidence interval, 96.2-99.1). A total of 1109 ceruloplasmin levels
      (20.8%) were ordered in the 1066 patients aged more than 55 years (none with
      Wilson disease). A "shotgun" approach to liver disease diagnosis was found:
      Ceruloplasmin was ordered on the same day as hepatitis B (81.0%), hepatitis C
      (76.0%), autoimmune hepatitis (75.1%), and hemochromatosis (73.1%). Of 424
      positive ceruloplasmin results, 91% were not pursued further. CONCLUSIONS:
      Guideline adherence restricts ceruloplasmin use to a population with a higher pre
      test probability of Wilson disease: patients with chronic liver disease aged 3 to
      55 years who have been tested for common causes of liver disease. The majority of
      the serum ceruloplasmin was measured in patients not indicated by the guidelines,
      resulting in poor test performance and wasted healthcare resources. Our data on
      ceruloplasmin use could serve as a touchstone for broader discussions on rational
      clinical decision making.

PMID- 23953877
TI  - Applying rapid 'de-facto' HTA in resource-limited settings: experience from
      Romania.
AB  - BACKGROUND: In attempting to constrain healthcare expenditure growth, health
      technology assessment (HTA) can enable policy-makers to look beyond budget impact
      and facilitate more rational decision-making. However lack of technical capacity
      and poor governance can limit use in some countries. Undertaking de facto HTA by
      adapting decisions taken in countries with established processes is a method that
      may be applied while building domestic HTA capacity. We explored the potential
      for applying this approach in Romania. METHODS: As part of a review of the basic
      health benefits available to insured Romanians we examined the listing process
      and content of the Romanian drug reimbursement formulary. We assessed value for
      money indirectly by drawing on appraisals by UK's NICE, and for products
      considered cost effective in the UK, adjusting prices by the ratio of Romanian
      per capita GDP to UK per capita GDP. FINDINGS: We found more than 30 of the top
      50 medicines on the Romanian formulary unlikely to be cost-effective, suggesting
      that existing external reference pricing mechanisms may not be delivering good
      value for money. CONCLUSIONS: While not taking into account local costs or
      treatment patterns, absent local considerations of value for money, this method
      offers a guide for both drug selection and pricing. Until robust local HTA
      processes are established this approach could support further analysis of
      existing prices and pricing mechanisms. Applied more generally, it is arguably
      preferable to external reference pricing, product delisting or arbitrary price
      cuts, and may support the future development of more rigorous, evidence-based
      decision-making.

PMID- 23953878
TI  - To what degree is the governance of Dutch hospitals orientated towards quality in
      care? Does this really affect performance?
AB  - INTRODUCTION: Changing health care systems and market competition requires
      hospital boards to shift their focus towards a systematic governance of the
      quality of care. The objective of our study was to describe hospital governance
      and the quality orientation in the Netherlands. Also we wished to investigate the
      relationship with hospital performance. MATERIALS AND METHODS: The chairs of both
      the boards of trustees and the management boards from all 97 Dutch hospitals were
      asked to participate in a cross-sectional study between November 2010 and
      February 2011. In this period data on their quality orientation were collected
      using a web-based survey. Data on hospital performance over the year 2010 were
      obtained in July 2011. RESULTS: A mixture of reforms and national guidelines
      increased the emphasis on quality governance in Dutch hospitals. Our results show
      that boards of trustees and management boards had a reasonable quality
      orientation. Boards were familiar with quality guidelines, received a reasonable
      amount of information related to quality and used this for monitoring quality and
      policy-making. However, we found no association between their quality orientation
      and hospital performance. CONCLUSION: There was a growing awareness of the
      quality of care among boards of trustees and management boards; yet some boards
      still lagged behind. Quality orientation is an important asset because receiving,
      reviewing and responding to the quality of their performance should provide
      opportunities to improve quality. However, we were not able to find a
      relationship between quality orientation and hospital performance. Future
      research should investigate how boards can develop quality management systems
      which in turn could enable medical professionals to optimise their delivery of
      care and thus its quality.

PMID- 23953879
TI  - Flavonoid intake and risk of CVD: a systematic review and meta-analysis of
      prospective cohort studies.
AB  - Observational studies have suggested that the intake of flavonoids is associated
      with a decreased risk of CVD. However, the results of these studies remain
      controversial. The aim of the present study was to evaluate the association
      between dietary flavonoid intake and CVD risk by conducting a systematic review
      of prospective cohort studies. Electronic reference databases were searched to
      identify studies that met the pre-stated inclusion criteria. The studies were
      assessed for eligibility and data were extracted by two authors independently.
      For each study, relative risks (RR) and 95 % CI were extracted and pooled using
      either a fixed-effects or a random-effects model. Generalised least-squares trend
      estimation analysis was used to evaluate dose-response relationships. The
      inclusion criteria were met by fourteen prospective cohort studies. The intakes
      of anthocyanidins (RR 0.89, 95 % CI 0.83, 0.96), proanthocyanidins (RR 0.90, 95 %
      CI 0.82, 0.98), flavones (RR 0.88, 95 % CI 0.82, 0.96), flavanones (RR 0.88, 95 %
      CI 0.82, 0.96) and flavan-3-ols (RR 0.87, 95 % CI 0.80, 0.95) were inversely
      associated with the risk of CVD when comparing the highest and lowest categories
      of intake. A similar association was observed for flavonol intake and CVD risk.
      Sensitivity and subgroup analyses further supported this association. The summary
      RR for CVD for every 10 mg/d increment in flavonol intake was 0.95 (95 % CI 0.91,
      0.99). The present systematic review suggests that the dietary intakes of six
      classes of flavonoids, namely flavonols, anthocyanidins, proanthocyanidins,
      flavones, flavanones and flavan-3-ols, significantly decrease the risk of CVD.

PMID- 23953880
TI  - Imatinib induces demethylation of miR-203 gene: an epigenetic mechanism of anti
      tumor effect of imatinib.
AB  - MicroRNA (miRNA) is an important regulator of cellular proliferation,
      differentiation and death. Leukemia-specific signature of miRNAs suggests that
      epigenetic dysregulation of miRNAs is important for leukemogenesis. We focused on
      the role of DNA methylation of miR-203 which targets BCR-ABL1 mRNA. The
      microarray analysis showed that 48 miRNAs of CpG-rich 212 miRNAs were upregulated
      over 2-fold after imatinib treatment. Imatinib induced the demethylation of the
      miR-203 promoter region, resulting in low expression of targeted BCR-ABL1 gene,
      and loss of proliferation of leukemic cells. In conclusion, demethylation of miR
      203 is one of the molecular mechanisms of imatinib-induced inhibition of BCR-ABL1
      positive leukemic cells. 

PMID- 23953881
TI  - Suppression of SERPINA1-albumin complex formation by galectin-3 overexpression
      leads to paracrine growth promotion of chronic myelogenous leukemia cells.
AB  - Galectin-3 is induced in chronic myelogenous leukemia (CML) cells by co-culture
      with bone marrow stromal cells, making paracrine growth promotion of CML cells in
      conditioned medium (CM) from galectin-3 overexpressing CML cells more potent. We
      used gel filtration chromatography to demonstrate that the bovine SERPINA1-fetal
      bovine serum albumin (BSA) complex was specifically suppressed in CM from
      galectin-3 overexpressing cells. The SERPINA1-BSA complex as well as human plasma
      SERPINA1 inhibited the growth of CML cells, while exogenous galectin-3 partly
      offset this effect. These findings suggest that galectin-3 overexpression
      promotes paracrine growth of CML cells by interfering with the action of the
      growth inhibitory SERPINA1-albumin complex. 

PMID- 23953882
TI  - Combination of vorinostat and low dose cytarabine for patients with azacitidine
      refractory/relapsed high risk myelodysplastic syndromes.
AB  - Outcome of patients with myelodysplastic syndrome after azacitidine failure is
      poor. In this population, we combined cytarabine (10-20mg/m2/day 14 days) with
      vorinostat (400mg/day) for escalating durations (7 days, 10 days and 14 days),
      and starting on day 1 (concomitant arm) or on day 14 (sequential arm) following a
      3+3 phase I design. 40 patients were treated. Dose limiting toxicities were all
      seen in sequential arm. The overall response rate was 15% with 4 responses in
      concomitant arm (ORR=25%). We conclude that this combination is tolerable and
      concomitant administration might be less toxic and have better therapeutic effect
      (clinicaltrials.gov NCT00776503).

PMID- 23953883
TI  - Caprin-1 is a novel microRNA-223 target for regulating the proliferation and
      invasion of human breast cancer cells.
AB  - MicroRNAs (miRNAs) are 21-22 nucleotides regulatory small non-coding RNAs that
      inhibit gene expression by binding to complementary sequences especially the 3'
      untranslated region (3'UTR) of mRNA. One miRNA can target many messenger RNAs,
      leading to a complex metabolic network. Previous studies have shown that miRNA
      223 regulates migration and invasion of tumor cells and targets cytoplasmic
      activation/proliferation-associated protein-1 (Caprin-1). In the present study,
      we detected the expression of miRNA-223 and Caprin-1 in MCF-7, T-47D and MDA-MB
      231 cancer cell lines, and MCF-10A normal breast cell line, and analyzed the role
      of miRNA-223 in Caprin-1-induced proliferation and invasion of human breast
      cancer cells. We found that miRNA-223 expression levels are significantly lower
      in MCF-7, T-47D and MDA-MB-231 cancer cells than in MCF-10A normal breast cells,
      while Caprin-1 expression is higher in cancer cells than in normal breast cells.
      The most malignant cancer cell line MDA-MB-231 has the lowest expression of miR
      223, but the highest expression of Caprin-1. Further, we found that miR-223
      targets the 3'UTR of Caprin-1 miRNA and down-regulates the expression of Caprin
      1. We also found that over-expression of Caprin-1 can promote the proliferation
      and the invasion of breast cancer cells, but miRNA-223 can inhibit the
      proliferation and the invasion. miRNA-223-induced inhibition can be reversed by
      ectopic over-expression of Caprin-1. These findings suggest that miR-223 may
      suppress the proliferation and invasion of cancer cells by directly targeting
      Caprin-1. Our study also indicates that expression levels of miR-223 and Caprin-1
      can be used to predict the state of cancer in breast cancer patient. 

PMID- 23953884
TI  - Clinical assessment of delayed gastric emptying and diabetic complications using
      gastric emptying scintigraphy: involvement of vascular disorder.
AB  - AIM: Delayed gastric emptying, including gastroparesis, is a common complication
      in diabetes mellitus. The association between delayed gastric emptying and
      overall diabetic complications remains to be studied in detail. We analysed this
      association. METHODS: We performed gastric emptying scintigraphy of (99m) Tc
      diethylenetriaminepentaacetic acid in 34 patients with diabetes to measure the
      gastric emptying half-times (T1/2) of the whole stomach (WS), proximal stomach
      (PS) and distal stomach (DS). We assessed T1/2, diabetic-related factors and
      complications. RESULTS: The prevalence of autonomic neuropathy was higher in the
      group with delayed T1/2 of the WS than in the normal group. Analysis of intima
      media thickness (IMT) and ankle brachial pressure index (ABI), which are risk
      indicators for vascular disorder, showed that IMT of the carotid bulb was greater
      in the group with delayed T1/2 of the WS than in the normal group (2.41 mm [1.50
      2.81] versus 1.40 mm [0.81-2.08], P = 0.015). T1/2 of the WS correlated
      positively with IMT of the carotid bulb (r = 0.391, P = 0.027) and negatively
      with ABI (r = -0.389, P = 0.028). These correlations were mainly attributed to PS
      and were the same in patients without autonomic neuropathy. In seven of nine
      patients who received scintigraphy again after diabetic treatment, glycosylated
      haemoglobin (HbA1c) levels decreased and T1/2 of the WS shortened compared with
      before treatment. CONCLUSION: Vascular disorder, among other cofactors such as
      autonomic neuropathy, could be involved in the pathophysiology of delayed gastric
      emptying. Medium- to long-term glycaemic control was associated with gastric
      emptying.

PMID- 23953885
TI  - Hidden genetic nature of epigenetic natural variation in plants.
AB  - Transcriptional gene silencing (TGS) is an epigenetic mechanism that suppresses
      the activity of repetitive DNA elements via accumulation of repressive chromatin
      marks. We discuss natural variation in TGS, with a particular focus on cases that
      affect the function of protein-coding genes and lead to developmental or
      physiological changes. Comparison of the examples described has revealed that
      most natural variation is associated with genetic determinants, such as gene
      rearrangements, inverted repeats, and transposon insertions that triggered TGS.
      Recent technical advances have enabled the study of epigenetic natural variation
      at a whole-genome scale and revealed patterns of inter- and intraspecific
      epigenetic variation. Future studies exploring non-model species may reveal
      species-specific evolutionary adaptations at the level of chromatin
      configuration. 

PMID- 23953886
TI  - Comparison of the clinical effectiveness of zanamivir and laninamivir octanoate
      for children with influenza A(H3N2) and B in the 2011-2012 season.
AB  - OBJECTIVES: To evaluate the clinical effectiveness of the two inhaled
      neuraminidase inhibitors (NAIs), zanamivir (ZN) and laninamivir octate (LO), for
      influenza A(H3N2) and B virus infections. DESIGN: A prospective, multicenter
      observational study was conducted from January to April in 2012. SETTING:
      Outpatients aged 5-18 years who had a temperature of 37.5 degrees C or higher and
      were diagnosed as having influenza based on an immunochromatographic assay were
      enrolled. SAMPLE: A total of 338 patients treated with ZN and 314 patients
      treated with LO were compared. MAIN OUTCOME MEASURES: The duration of fever after
      administration of the first dose of each NAI was evaluated as a primary endpoint.
      The secondary endpoint was episodes of biphasic fever. RESULTS: No statistically
      significant difference in the duration of fever was found between the ZN and LO
      groups (log-rank test, P = 0.117). A logistic regression model showed that
      episodes of biphasic fever increased by 1.19 times for every decrease of 1 year
      of age (P = 0.016) and that the number of biphasic fever episodes in patients
      treated with LO was 5.80-times greater than that in patients treated with ZN (P <
      0.001). CONCLUSIONS: Although the duration of fever in the LO group was
      comparable to that in the ZN group, episodes of biphasic fever were more frequent
      in younger children and in the LO group than in the ZN group.

PMID- 23953887
TI  - Glutathione S-transferase P1 mRNA expression in plasma cell disorders and its
      correlation with polymorphic variants and clinical outcome.
AB  - BACKGROUND: Glutathione S-transferase P1 (GSTP1) is an important phase II enzyme
      involved in detoxification of carcinogens. GSTP1 gene overexpression has been
      observed in a variety of human cancers but there are no studies in plasma cell
      disorders. The aim of this study was to examine GSTP1 mRNA expression level in
      multiple myeloma (MM) and monoclonal gammopathy of undetermined significance
      (MGUS). In addition, we have determined GSTP1 polymorphic variants in order to
      estimate MM risk and their relationship with the expression level. Results were
      also correlated with laboratory parameters and clinical outcome. METHODS: Bone
      marrow mononuclear cells from 125 patients with plasma cell disorders were
      studied. Peripheral blood samples of 110 age and sex matched healthy controls
      were also evaluated. Real-Time Quantitative RT-PCR and PCR-RFLP assays were used.
      RESULTS: Upregulation of GSTP1 was observed in 37.7% MM and in 22.6% MGUS
      patients. A significant increase of GSTP1 expression in MM with respect to MGUS
      was detected (p=0.0427). Most MM patients that achieved complete remission had
      low transcription levels (77.8%) compared to those who did not reach this
      condition (44.4%) (p=0.0347). GSTP1 heterozygous carriers showed reduced
      expression compared to those with homozygous wild type genotype (p=0.0135).
      CONCLUSION: Our findings suggest, for the first time, a role for GSTP1 expression
      in development and/or progression of plasma cell disorders, and a probable
      influence of functional capacity of the enzyme on clinical outcome. These results
      and those of the literature support GSTP1 as an interesting tumor marker and a
      potential therapeutic target.

PMID- 23953888
TI  - Comparative pharmacokinetic profiles of a novel isotretinoin formulation
      (isotretinoin-Lidose) and the innovator isotretinoin formulation: a randomized, 4
      treatment, crossover study.
AB  - BACKGROUND: A high-fat meal is needed for optimal absorption of isotretinoin. A
      new formulation of isotretinoin, which enhances absorption of isotretinoin in the
      absence of dietary fat, has recently been approved by the Food and Drug
      Administration (FDA). OBJECTIVE: We sought to compare the pharmacokinetic
      profiles of a new formulation of isotretinoin (isotretinoin-Lidose) with the
      innovator isotretinoin formulation. METHODS: This study was an open-label, single
      dose, randomized, 4-treatment, crossover comparative trial between a new and
      innovator formulation of isotretinoin in the fasting and fed states. RESULTS:
      Both formulations were bioequivalent under fed conditions. As expected in a
      fasting state, absorption of both formulations was reduced. A considerable
      difference between the 2 drugs occurred under fasted conditions-there was a
      marked improvement in overall bioavailability of the isotretinoin-Lidose
      formulation. Mean plasma levels of the isotretinoin-Lidose formulation during
      fasting reached 66.8% of that observed with a fatty meal, and those of the
      isotretinoin formulation only reached 39.6% of that observed with a fatty meal.
      LIMITATIONS: Only the FDA-stipulated standard high-fat, high-calorie meal of 50-g
      fat was studied in the fed state. CONCLUSION: Isotretinoin-Lidose formulation is
      bioequivalent to the innovator formulation under fed conditions with regard to
      its pharmacokinetic profile but delivers twice as much isotretinoin and 4-oxo
      isotretinoin when administered after an overnight fast.

PMID- 23953889
TI  - HIV latency and integration site placement in five cell-based models.
AB  - BACKGROUND: HIV infection can be treated effectively with antiretroviral agents,
      but the persistence of a latent reservoir of integrated proviruses prevents
      eradication of HIV from infected individuals. The chromosomal environment of
      integrated proviruses has been proposed to influence HIV latency, but the
      determinants of transcriptional repression have not been fully clarified, and it
      is unclear whether the same molecular mechanisms drive latency in different cell
      culture models. RESULTS: Here we compare data from five different in vitro models
      of latency based on primary human T cells or a T cell line. Cells were infected
      in vitro and separated into fractions containing proviruses that were either
      expressed or silent/inducible, and integration site populations sequenced from
      each. We compared the locations of 6,252 expressed proviruses to those of 6,184
      silent/inducible proviruses with respect to 140 forms of genomic annotation, many
      analyzed over chromosomal intervals of multiple lengths. A regularized logistic
      regression model linking proviral expression status to genomic features revealed
      no predictors of latency that performed better than chance, though several
      genomic features were significantly associated with proviral expression in
      individual models. Proviruses in the same chromosomal region did tend to share
      the same expressed or silent/inducible status if they were from the same cell
      culture model, but not if they were from different models. CONCLUSIONS: The
      silent/inducible phenotype appears to be associated with chromosomal position,
      but the molecular basis is not fully clarified and may differ among in vitro
      models of latency.

PMID- 23953890
TI  - Dynamics of serum metabolites in patients with chronic hepatitis C receiving
      pegylated interferon plus ribavirin: a metabolomics analysis.
AB  - OBJECTIVES: Serum samples from patients with chronic hepatitis C were subjected
      to metabolomics analysis to clarify the pretreatment characteristics of their
      metabolites and also changes in specific metabolites resulting from antiviral
      therapy with pegylated interferon plus ribavirin (PegIFN/RBV). MATERIALS/METHODS:
      The serum levels of low-molecular-weight metabolites in the twenty patients
      before and 24weeks after completion of PegIFN/RBV therapy were analyzed using
      capillary electrophoresis and liquid chromatography-mass spectrometry. RESULTS:
      Ten patients showed a non-virological response (NVR) and 10 achieved a sustained
      virological response (SVR) with eradication of viremia. The pretreatment levels
      of tryptophan were significantly higher in the patients of SVR than in those of
      NVR (p=0.010). The area under the curve (AUC) value of tryptophan calculated from
      the receiver operating characteristic (ROC) curve for discriminating SVR from NVR
      was 0.84 (95% confidential interval, 0.66-1.02, p=0.010). The ROC curve of
      multiple logistic regression model incorporating the pretreatment levels of
      tryptophan and gamma-glutamate-arginine showed that the AUC value was highly
      significant (AUC=0.92, 95% confidential interval, 0.79-1.05, p=0.002). Twenty
      four weeks after completion of treatment, the levels of gamma-glutamyl
      dipeptides, glutamic acid, 5-oxoproline, glucosamine and methionine sulfoxide
      were decreased, whereas those of 5-methoxy-3-indoleacetate, glutamine, kynurenine
      and lysine were increased significantly (p<0.05) in both the NVR and SVR
      patients. CONCLUSIONS: The pretreatment serum levels of certain metabolites
      including tryptophan are associated with the response to PegIFN/RBV therapy.
      PegIFN/RBV therapy can ameliorate the oxidative stress responsible for
      glutathione metabolism.

PMID- 23953891
TI  - Branched chain and aromatic amino acids change acutely following two medical
      therapies for type 2 diabetes mellitus.
AB  - OBJECTIVE: Elevated circulating levels of branched chain and aromatic amino acids
      (BCAA/AAAs) are associated with insulin resistance and incident type 2 diabetes
      (T2D). BCAA/AAAs decrease acutely during an oral glucose tolerance test (OGTT), a
      diagnostic test for T2D. It is unknown whether changes in BCAA/AAAs also signal
      an early response to commonly used medical therapies for T2D. MATERIALS AND
      METHODS: A liquid chromatography-mass spectrometry approach was used to measure
      BCAA/AAAs in 30 insulin sensitive (IS) and 30 insulin resistant (IR) subjects
      before and after: (1) one dose of a sulfonylurea medication, glipizide, 5 mg
      orally; (2) two days of twice daily metformin 500 mg orally; and (3) a 75-g OGTT.
      Percent change in BCAA/AAAs was determined after each intervention. RESULTS:
      Following glipizide, which increased insulin and decreased glucose in both
      subject groups, BCAA/AAAs decreased in the IS subjects only (all P<0.05).
      Following metformin, which decreased glucose and insulin in only the IR subjects,
      4 BCAA/AAAs increased in the IR subjects at or below P=0.05, and none changed in
      the IS subjects. Following OGTT, which increased glucose and insulin in all
      subjects, BCAA/AAAs decreased in all subjects (P<0.05). CONCLUSIONS: BCAA/AAAs
      changed acutely during glipizide and metformin administration, and the magnitude
      and direction of change differed by the insulin resistance status of the
      individual and the intervention. These results indicate that BCAA/AAAs may be
      useful biomarkers for monitoring the early response to therapeutic interventions
      for T2D.

PMID- 23953892
TI  - Early and late menarche are associated with oligomenorrhea and predict metabolic
      syndrome 26 years later.
AB  - OBJECTIVE: We determined whether simple, clinical information on late and early
      menarche could help identify adult women with metabolic syndrome (MetS) and
      oligomenorrhea. MATERIALS/METHODS: We carried out a 26-year prospective follow-up
      of 272 suburban schoolgirls from ages 5-22 to 30-46. RESULTS: Early menarche
      (<=10 years, 5.2% of girls) and late menarche (>=16 years, 6.7% of girls) were
      both associated with oligomenorrhea (>=42 days) in adulthood, 29% and 11%, vs. 5%
      for normal menarche (11-15 years), p=.004. Early menarche was characterized by
      high childhood BMI (LS mean+/-SE: 21.2 +/-1.0 kg/m2) and by high childhood and
      adult MetS (15%, 36%). Girls with late menarche had the lowest childhood BMI
      (18.1+/-1.0), no childhood MetS, and the highest adult MetS (47%). Increasing age
      at menarche was associated with uniformly decreasing childhood BMI and MetS, but
      with a U-shaped pattern of BMI (p = .05), MetS (p=.008), and oligomenorrhea
      (p=.02) in adulthood. Change to MetS from median ages 13 to 38 was associated
      with early-late menarche (OR=3.11, 95% CI 1.37-7.07, p=.007). MetS in adulthood
      was associated with childhood MetS (OR=8.03, 95% CI 2.57-25.08, p=.0003) and with
      early-late menarche (OR =3.43, 95% CI 1.44-8.15, p=.005). CONCLUSIONS: Menarche
      age had a curvilinear ('U' shaped) relationship with MetS and oligomenorrhea in
      adulthood. Late menarche and early menarche are risk factors for adult
      oligomenorrhea, MetS, and cardiometabolic abnormalities. Girls with early (<= age
      10) and with late menarche (>= 16) represent a group at high risk for adult
      cardiometabolic abnormalities and oligomenorrhea that is easily identifiable by
      physicians.

PMID- 23953893
TI  - Pelagic microplastics around an archipelago of the Equatorial Atlantic.
AB  - Plastic marine debris is presently widely recognised as an important
      environmental pollutant. Such debris is reported in every habitat of the oceans,
      from urban tourist beaches to remote islands and from the ocean surface to
      submarine canyons, and is found buried and deposited on sandy and cobble beaches.
      Plastic marine debris varies from micrometres to several metres in length and is
      potentially ingested by animals of every level of the marine food web. Here, we
      show that synthetic polymers are present in subsurface plankton samples around
      Saint Peter and Saint Paul Archipelago in the Equatorial Atlantic Ocean. To
      explain the distribution of microplastics around the Archipelago, we proposed a
      generalised linear model (GLM) that suggests the existence of an outward gradient
      of mean plastic-particle densities. Plastic items can be autochthonous or
      transported over large oceanic distances. One probable source is the small but
      persistent fishing fleet using the area. 

PMID- 23953894
TI  - The value of the seagrass Posidonia oceanica: a natural capital assessment.
AB  - Making nature's value visible to humans is a key issue for the XXI century and it
      is crucial to identify and measure natural capital to incorporate benefits or
      costs of changes in ecosystem services into policy. Emergy analysis, a method
      able to analyze the overall functioning of a system, was applied to reckon the
      value of main ecosystem services provided by Posidonia oceanica, a fragile and
      precious Mediterranean seagrass ecosystem. Estimates, based on calculation of
      resources employed by nature, resulted in a value of 172 ? m(-2)a(-1). Sediment
      retained by meadow is most relevant input, composing almost the whole P. oceanica
      value. Remarks about economic losses arising from meadow regression have been
      made through a time-comparison of meadow maps. Suggested procedure represents an
      operative tool to provide a synthetic monetary measure of ecosystem services to
      be employed when comparing natural capital to human and financial capitals in a
      substitutability perspective.

PMID- 23953895
TI  - Efficacy of extracorporeal shockwave therapy for knee osteoarthritis: a
      randomized controlled trial.
AB  - BACKGROUND: Extracorporeal shockwave therapy (ESWT) has been widely used for pain
      relief and treatment of musculoskeletal disorders. We aimed to assess ESWT for
      knee osteoarthritis (OA) over 12 wk by comparison with placebo treatment.
      MATERIALS AND METHODS: We randomized 70 patients to receive placebo (n = 36) or
      ESWT (n = 34). For ESWT, patients received 4000 pulses of shockwave at 0.25
      mJ/mm(2) weekly for 4 wk. In the placebo group, patients received shockwave at 0
      mJ/mm(2) in the same area. The effect on OA was assessed by pain on a visual
      analog scale and disability on the Lequesne index, Western Ontario and McMaster
      University Osteoarthritis Index, and patient perception of the clinical severity
      of OA. Evaluation was performed at baseline and after 1, 4, and 12 wk. RESULTS:
      We found no adverse events during and after ESWT. ESWT was more effective than
      placebo in reducing pain on movement at each period (P < 0.01). The mean visual
      analog scale score with ESWT was 3.83 at 12 wk versus 7.56 at baseline (P <
      0.01). The Lequesne index and the Western Ontario and McMaster University
      Osteoarthritis Index score were reduced with ESWT. Moreover, patient perception
      of clinical severity of OA was significantly greater with ESWT than that with
      placebo (P < 0.01). CONCLUSIONS: ESWT is effective in reducing pain and improving
      knee function, with better results than placebo during the 12-wk treatment.
      However, further pilot studies are needed to determine whether ESWT should be
      recommended at an early or later stage of OA or combined with conventional
      therapies.

PMID- 23953897
TI  - State of the industry.

PMID- 23953898
TI  - New anticoagulants.

PMID- 23953896
TI  - Development of venovenous extracorporeal blood purification circuits in rodents
      for sepsis.
AB  - BACKGROUND: Unlike pharmacologic interventions in sepsis, extracorporeal blood
      purification, which is widely used in septic patients, is not typically studied
      in experimental rodents. Most of the previous studies have performed
      extracorporeal blood purification in larger animals and typically use
      arteriovenous (AV) vascular access. We developed a venovenous (VV) purification
      model in the rat as an adjunct for the treatment of sepsis. METHODS: Using adult
      male Sprague-Dawley rats, we cannulated the femoral artery or vein and the
      jugular vein with P50 tubing and created an AV or VV circuit. Blood flow was
      maintained by arterial pressure in the AV circuit, whereas in the VV circuit the
      blood flow was regulated using a rotary pump. The safety of this circuit was
      evaluated using the changes of blood interleukin 6, rectal temperature, and 7-d
      survival with sham extracorporeal circulation (circuit connection without
      treatment) compared with the control (without circuit). The main side
      complications of this VV circuit were compared with those of the AV circuit.
      RESULTS: The differences in interleukin 6, body temperature, and cumulative
      survival were not statistically significant after extracorporeal circulation. The
      main complications of extracorporeal circulation occurred less often with VV
      compared with AV therapy: massive bleeding (2.5% versus 15%, P = 0.04); clot
      formation (2.5% versus 15%, P = 0.04). This VV circuit has been successfully used
      in different septic rodent models with different techniques (hemoadsorption and
      hemofiltration). CONCLUSIONS: VV blood purification in a rodent model appears to
      be effective and is safer than AV circuit.

PMID- 23953899
TI  - Disadvantages of VKA and requirements for novel anticoagulants.
AB  - Vitamin K antagonists have been in wide use for over 70 years. Warfarin, the most
      commonly used vitamin K antagonist, has been shown to be highly effective in
      treating and preventing thrombosis. Despite this, warfarin has many
      disadvantages, which has led to the development of a new class of oral
      anticoagulants targeted to specific coagulation factors designated as target
      specific oral anticoagulants (TSOAs). TSOAs include the thrombin inhibitors
      (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban). This chapter
      reviews the disadvantages of warfarin and evaluates both the advantages and
      disadvantages of the new oral anticoagulants. 

PMID- 23953900
TI  - Novel oral anticoagulants in non-valvular atrial fibrillation.
AB  - Atrial fibrillation (AF) confers a significant risk of stroke or systemic
      thromboembolism. Oral anticoagulation is the most effective therapy for AF
      related stroke prevention. A decision to advise oral anticoagulation should be
      based upon the individual absolute risks of stroke and bleeding, and almost all
      AF patients with >=1 stroke risk factors have a positive net clinical benefit of
      oral anticoagulation. The novel oral anticoagulants (NOACs) dabigatran,
      rivaroxaban and apixaban are more convenient, and are at least equally effective
      and safer (regarding bleeding complications) for stroke prevention compared with
      vitamin K antagonists (VKAs). Availability of NOACs and improved stroke and
      bleeding risks assessment should increase the number of AF patients who receive
      adequate thromboprophylaxis. In this review article, we present an overview of
      the clinical phase III trials with NOACs for stroke prevention and discuss the
      contemporary principles of thromboprophylaxis in AF patients with various stroke
      and bleeding risk profiles, as well as practical aspects of NOACs therapy. 

PMID- 23953901
TI  - Novel oral anticoagulants in secondary prevention of stroke.
AB  - In patients with atrial fibrillation (AF) oral anticoagulation with vitamin-K
      antagonists (warfarin, phenprocoumon) is effective both for primary and secondary
      stroke prevention yielding a 60-70% relative reduction in stroke risk compared
      with placebo, as well as a mortality reduction of 26 percent. Vitamin-K
      antagonists have a number of well documented shortcomings. Recently the results
      of randomised trials for three new oral anticoagulants that do not exhibit the
      limitations of vitamin-K antagonists have been published. These include direct
      factor Xa inhibitors (rivaroxaban and apixaban) and a direct thrombin inhibitor
      (dabigatran). The studies (RE-LY, ROCKET-AF, ARISTOTLE, AVERROES) provide
      promising results for the new agents, including higher efficacy and a
      significantly lower incidence of intracranial bleeds compared with warfarin or
      aspirin. The new drugs show similar results in secondary as well as in primary
      stroke prevention in patients with AF. Apixaban was demonstrated to be clearly
      superior to aspirin and had the same rate of major bleeding complications. Meta
      analyses show that the novel anticoagulants are superior to warfarin for the
      reduction of stroke, major bleeding and intracranial bleeds. New anticoagulants
      add to the therapeutic options for patients with AF, and offer a number of
      advantages over warfarin, for both the clinician and patient, including a
      favorable bleeding profile and convenience of use. Aspirin is no longer an option
      in secondary stroke prevention in patients with atrial fibrillation.
      Consideration of these new anticoagulants will improve clinical decision making. 

PMID- 23953902
TI  - New oral anticoagulants after acute coronary syndrome.
AB  - New oral anticoagulants (NOACs) have been developed that may further decrease the
      mortality and morbidity of ACS by complementing antiplatelet therapy. Optimal use
      of these agents can be achieved by maximum reduction in thrombotic events at the
      minimum bleeding risk when combining a long-term oral anticoagulant with anti
      platelet therapy in patients with coronary heart disease. Although, based on the
      pharmacokinetics and -dynamics of NOACs, these agents could improve the current
      management of ACS patients, multiple trials consistently demonstrate a trend
      toward increased major and clinically relevant non major bleeding almost
      diminishing the benefits in reduction of ischemic events. Therefore, some
      critical issues need to be further evaluated in future trials. 

PMID- 23953903
TI  - New oral anticoagulants for the treatment of venous thromboembolism.
AB  - New oral anticoagulants, acting either as direct factor-Xa or thrombin
      inhibitors, have been evaluated for the acute and long-term treatment of venous
      thromboembolism (VTE). Dabigatran and rivaroxaban are as effective as
      conventional therapy (heparin/vitamin K antagonists) without safety concerns.
      Rivaroxaban allows a single-drug regimen even in patients with pulmonary
      embolism, while dabigatran requires 5-7 days of initial heparin treatment. The
      results of clinical trials with apixaban and edoxaban will become available in
      the coming months. Rivaroxaban, apixaban and dabigatran are more effective than
      placebo for the extended treatment of VTE. Apixaban is effective in both
      therapeutic and prophylactic doses. Considering both efficacy and bleeding
      complications, all these agents have a favorable net clinical benefit. Dabigatran
      is as effective and safe as warfarin for the extended treatment of VTE. It is
      conceivable that the new oral anticoagulants will become the standard therapy for
      VTE in the next years. 

PMID- 23953904
TI  - New anticoagulants in the treatment of patients with cancer-associated venous
      thromboembolism.
AB  - Venous thromboembolism (VTE) represents a common source of morbidity and
      mortality among patients with malignant disease. In this specific setting, the
      treatment of VTE is challenging as cancer patients display a high tendency to
      develop recurrent VTE, as well as anticoagulant-related bleeding complications.
      Low-molecular-weight heparins have been demonstrated to be more effective in the
      long-term prevention of recurrent VTE in cancer patients compared with
      conventional treatment with vitamin K antagonists. A limitation of this
      therapeutic approach includes the long-term requirement of daily subcutaneous
      injections, which may be burdensome to patients. Over the past decade, several
      novel oral anticoagulants have emerged, which can be administered in fixed doses
      without the need for monitoring. Clinical trials evaluating these agents for
      treatment in the general VTE population yielded promising results. This review
      summarizes the current management of cancer-associated VTE, overviews the trials
      that investigated the novel anticoagulant drugs for the treatment of acute VTE
      and discusses the potential of these novel agents for use in cancer patients. 

PMID- 23953905
TI  - Novel oral anticoagulants for thromboprophylaxis after orthopaedic surgery.
AB  - The direct thrombin inhibitor, dabigatran, and the selective factor Xa
      inhibitors, rivaroxaban and apixaban, are new oral anticoagulants that are
      approved in many countries for prevention of venous thromboembolism in patients
      undergoing elective hip or knee arthroplasty. All have a rapid onset of action, a
      low potential for food and drug interactions and a predictable anticoagulant
      effect that obviates the need for routine coagulation monitoring. These agents
      offer a convenient alternative to conventional anticoagulant drug regimens,
      including parenteral low-molecular-weight heparins and fondaparinux, and oral
      adjusted-dose vitamin K antagonists, for the prevention of venous thromboembolism
      in this surgical setting. This review summarizes the pharmacology, clinical trial
      results, bleeding risk and practical use of these new oral anticoagulants in
      clinical orthopaedic practice. Potential issues to be considered when using these
      oral anticoagulants include renal impairment, potential drug interactions,
      neuraxial anaesthesia and management of bleeding. 

PMID- 23953906
TI  - NOACs for thromboprophylaxis in medical patients.
AB  - The risk of venous thrombosis extends for an indeterminate length of time
      following admission to hospital with a medical or surgical condition.
      Observational studies in surgery show this risk extends for months and perhaps
      more than one year, for medical patients the risk extends for at least several
      weeks. Large bodies of evidence support the heightened risk status of
      hospitalised surgical and medical patients, and that prophylactic measures
      significantly reduce the risk of thrombosis. Extending thromboprophylaxis for 4-6
      weeks with anticoagulants both old and new has been shown to be efficacious and
      safe in surgical patients. However in populations of medical patients although
      prolonged anticoagulant thromboprophylaxis has been shown to be efficacious it
      also results in more bleeding and the risk benefit is not clear. Hence no
      therapies are approved for prolonged thromboprophylaxis in medical patients. In
      this area there have been one phase III study of low molecular weight heparin and
      two completed phase III studies of NOACs. This article briefly summarises our
      understanding of the background to preventing venous thromboembolism in
      hospitalised medical patients and reviews the details of the studies using NOACs.

PMID- 23953907
TI  - Bleeding and antidotes in new oral anticoagulants.
AB  - In the past decade, several new oral anticoagulants (NOACs) have been studied and
      approved for the prophylaxis and treatment of arterial and venous
      thromboembolism. These agents were shown to be as effective as or better than
      warfarin and resulted in comparable or lower bleeding rates than warfarin.
      Specific antidotes for the reversal of the anticoagulant effect of these drugs,
      such as monoclonal antibodies against the direct thrombin inhibitor dabigatran or
      recombinant Xa-analog in the case of factor Xa inhibitors, are still being
      investigated in early clinical trials. In certain situations, as in case of
      emergency surgery or life-threatening major bleeding, a rapid reversal strategy
      is needed. Several non-specific prohemostatic agents or coagulation factor
      concentrates have been suggested as potential candidates for the reversal of
      NOACs, but the evidence supporting these agents was mainly derived from small
      animal studies, or is based on partial or complete correction of laboratory
      parameters in healthy volunteers treated with these agents. Activated prothrombin
      complex concentrate seems promising for the reversal of dabigatran, while non
      activated prothrombin complex concentrates have potential for the reversal of
      anti-factor Xa. The risk of thromboembolic complications requires careful
      evaluation. In this article, the evidence- or the lack of it - supporting the use
      of the different prohemostatic agents for the management of bleeding and for
      reversal of the different classes of NOACs is discussed. 

PMID- 23953908
TI  - New developments in parenteral anticoagulation for arterial and venous
      thromboembolism.
AB  - The efficacy and safety of heparin and low-molecular-weight heparins (LMWHs) are
      well documented in venous and arterial thromboembolism. Several drawbacks of
      heparins have inspired the development of newer parenteral anticoagulants for
      specific indications, including heparin-induced thrombocytopenia (HIT) and
      percutaneous coronary interventions (PCI). The direct thrombin inhibitors
      recombinant hirudin and argatroban are now established alternatives for HIT
      patients, and bivalirudin is one of the most used anticoagulants in PCI. The
      pentasaccharide fondaparinux is an alternative for LMWH for thromboprophylaxis in
      various clinical settings and for patients with an acute coronary syndrome (ACS)
      not scheduled for PCI. In Europe, it was recently approved for treatment of
      superficial vein thrombosis. Further development of new parenteral anticoagulants
      is slow and the emphasis has shifted towards development of new oral
      anticoagulants and antiplatelet drugs. Still, promising new anticoagulants, some
      targeting less conventional targets in the coagulation system, have been
      developed and will undergo further clinical evaluation. 

PMID- 23953909
TI  - New oral anticoagulants in elderly patients.
AB  - The new oral anticoagulants (NOACs) dabigatran etexilate, rivaroxaban, and
      apixaban have been extensively studied for prevention and treatment of venous
      thromboembolic disease and for stroke prevention in atrial fibrillation. Elderly
      patients have the highest incidence of thrombotic complications but also have the
      highest risk of anticoagulant associated bleeding. In this review we critically
      examine the balance between risks and benefits of NOACs compared with vitamin K
      antagonists in elderly patients enrolled in phase 3 randomized controlled trials
      for the management of venous thrombosis and stroke prevention in atrial
      fibrillation. Results show that the favourable balance between risks and benefits
      of NOACs is preserved in the elderly population. 

PMID- 23953910
TI  - Cost-effectiveness of new oral anticoagulants in the prevention of stroke in
      patients with atrial fibrillation.
AB  - Atrial fibrillation (AF) is a common arrhythmia and the leading cause of stroke,
      an event with high human and economic burden. Novel oral anticoagulants have been
      approved in many markets as alternatives to warfarin for stroke prevention in
      patients with AF - dabigatran etexilate, apixaban and rivaroxaban. Given the high
      burden of AF, and given that new treatments can more effectively prevent stroke
      than warfarin, but at higher drug cost, there has been a need for systematic
      evaluation of the costs and benefits of these new treatments. In this study, we
      summarize the findings of a systematic literature review on the cost
      effectiveness of the new oral anticoagulants. We find that there is substantial
      heterogeneity between the studies and their numerical findings, despite using a
      common set of four trials for their clinical inputs. However, there is broad
      consensus among them that each of the novel oral anticoagulants is cost-effective
      versus warfarin or aspirin.

PMID- 23953911
TI  - Vitamin C and E supplementation during pregnancy.

PMID- 23953912
TI  - DNA damage and oxidative stress in patients with mild preeclampsia and offspring.
AB  - OBJECTIVE: Oxidative stress has been shown to play an important role in the
      pathogenesis of pre-eclampsia, and DNA damage frequently occurs in cells exposed
      to such stress. The aim of the present study was to investigate DNA damage and
      oxidative stress in mildly pre-eclamptic women and their offspring. STUDY DESIGN:
      We studied 25 mildly pre-eclamptic mothers, 20 healthy controls, and their
      infants. Mononuclear leukocyte DNA damage, total antioxidant status (TAS), and
      total oxidant status (TOS) were determined and the oxidative stress index (OSI)
      was calculated. RESULTS: DNA damage, and TOS and OSI levels were significantly
      increased, and TAS levels significantly decreased, in maternal and cord blood
      samples of the mildly pre-eclamptic group. A positive correlation between the
      extent of DNA damage and diastolic blood pressure was evident in pre-eclamptic
      mothers and there was a negative correlation between the extent of DNA damage and
      TOS. CONCLUSION: Both oxidative stress and DNA damage are elevated in mildly pre
      eclamptic patients and their offspring. Increased oxidative stress may be
      important in inducing DNA damage in pre-eclamptic patients.

PMID- 23953913
TI  - HPV vaccination coverage in French girls attending middle and high schools: a
      declarative cross sectional study in the department of Cote d'Or.
AB  - OBJECTIVES: To assess human papillomavirus prophylactic vaccine coverage among a
      representative population of French girls, aged 14 years and above, attending
      middle and high schools, and to determine factors associated with the initiation
      and completion of the vaccination protocol. STUDY DESIGN: This cross-sectional
      study, designed with cluster sampling, was conducted from October 2010 to May
      2011, in 29 schools in the department of Cote d'Or, France. The schools were
      randomized according to their status (public or private) and location (rural or
      urban). Two classes per level were then included. All analyses were stratified on
      age. RESULTS: 948 questionnaires were collected (87.9% participation). Mean age
      was 15.2 years (SD=1.3), ranging between 14 and 19. Only 31.7% of 14-year-old
      girls and 61.4% of girls aged 15 and above initiated vaccination (one dose), and
      7.8% of 14-year-old girls and 48.5% of girls aged 15 and above completed it
      (three doses). An urban school location and a physician's recommendation were
      independently associated with vaccination initiation in girls aged 14. In girls
      aged 15 and above, the parents' socioeconomic status, the family composition and
      a recommendation by a physician were independently associated with vaccination
      initiation. Once vaccination had been initiated, girls who attended private
      school, who belonged to families with higher outcomes, who lived with a single
      parent or who smoked were less likely to complete the vaccination protocol.
      CONCLUSION: HPV prophylactic vaccine coverage in girls attending school in Cote
      d'Or appears to be low. Physicians play a major role in vaccine acceptance.

PMID- 23953914
TI  - Hypermethylation of two CpG sites upstream of CASP8AP2 promoter influences gene
      expression and treatment outcome in childhood acute lymphoblastic leukemia.
AB  - DNA hypermethylation of Caspase 8 associated protein 2 (CASP8AP2) and its role in
      childhood acute lymphoblastic leukemia (ALL) is unclear. We analyzed methylation
      status of CpG sites upstream of CASP8AP2 gene in 86 children with ALL by
      bisulfite sequencing and quantitative PCR. Methylation percentage of two CpG
      sites at positions of -1189 and -1176 was inversely correlated with mRNA
      expression (Spearman correlation: -0.333, P=0.002). High methylation was
      associated with the existence of minimal residual disease (MRD) at day 78
      (P=0.035), The patients in high methylation group had a poor treatment outcome.
      The combination of methylation level and MRD at day 33 might improve current risk
      stratification. 

PMID- 23953915
TI  - Does monocyte count have prognostic significance in cancer?

PMID- 23953916
TI  - Heterogeneity of letter fluency impairment and executive dysfunction in
      Parkinson's disease.
AB  - Letter fluency deficits are commonly detected in non-demented Parkinson's disease
      (PD) patients but the underlying cause remains uncertain. We investigated the
      role of slowed processing speed and executive dysfunction. Eighteen nondemented
      PD participants and nineteen controls were compared on letter fluency using a
      fluency index (Fi); the average time to "think" of each word, a measure
      independent of motor speed. Video analyses produced thinking times to switch
      between word clusters and generate a word within a cluster. Correlational and
      regression analyses were undertaken with tests of processing speed and executive
      functioning. The PD group exhibited significantly longer fluency indices than
      controls across all components. Performance on tests of executive functioning
      explained a significant proportion of variance whereas performance in processing
      speed tests did not. Moreover, PD participants with an executive functioning
      impairment showed significantly worse switching fluency indices only compared
      with Controls and PD participants without executive dysfunction. PD participants
      with executive dysfunction exhibited a disproportionate impairment in the time
      taken to switch between clusters than to think of words within clusters.
      Executive functioning contributed to fluency performance more than processing
      speed. Cognitive heterogeneity and motor slowing, may mask the profile of
      cognitive dysfunction in neurodegenerative disease.

PMID- 23953917
TI  - Clostridium difficile infection after lung transplantation: are we really doing
      everything possible?

PMID- 23953918
TI  - Extended criteria donor lungs and clinical outcome: results of an alternative
      allocation algorithm.
AB  - BACKGROUND: Despite the scarcity of donor lungs, most potential donor organs are
      not offered by organ procurement organizations or are turned down by transplant
      centers because no suitable recipient is found according to regular allocation.
      Although extended criteria donors (ECDs) have recently been considered by many
      programs, the lung utilization rate remains < 30% in most countries. The
      allocation policy of Eurotransplant for donor lungs that have been turned down
      for donor-related medical reasons by 3 centers is to attempt a rescue offer, for
      which centers choose the recipients themselves. At Hannover Medical School we
      systematically divert these organs to more stable recipients to avoid adverse
      transplant outcomes. We follow up on these transplants and compare them with
      those following regular allocation. METHODS: This study is an analysis of all
      organ offers and corresponding recipients at our center during the period from
      January 2010 to August 2011. RESULTS: A total of 183 lung transplantations were
      performed, 111 regular donor lung offers were accepted for their intended
      recipient, whereas a total of 72 rescue lung offers, including all extended
      criteria donors, were accepted for recipients selected by our center. Donor
      characteristics differed between the 2 groups accordingly. Median age of ECD
      organ donors was significantly higher than that of regular donors (46.0 [IQR 21]
      vs 40.0 [IQR 22] years, p = 0.02). Donor mechanical ventilation time did not
      differ (3.5 +/- 4.8 vs 3.0 +/- 4.0 days, p = 0.33, not statistically significant
      [NS]). Donor oxygenation ratio (PaO2:FIO2) at time of organ offer was
      significantly lower (398.3 +/- 110.3 vs 423.0 +/- 97.6 mm Hg, p = 0.02).
      Recipients of rescue allocation organs were older than regularly selected
      recipients (53.7 +/- 11.7 vs 46.7 +/- 15.4 years, p = 0.0003), needed a shorter
      time for mechanical ventilation post-operatively (19.5 +/- 306.6 vs 68.5 +/-
      718.8 hours, p = 0.02), and had shorter hospital stays (24.0 +/- 23.4 vs 47.0 +/-
      43.4 days, p > 0.0001). Intensive care stay length did not differ significantly
      (2.0 +/- 14.5 vs 5.0 +/- 23.7 days, p = 0.21 [NS]). Post-operative survival up to
      27 months after transplantation was not worse in recipients receiving rescue
      allocation when compared with standard allocation lung offers (81.62% vs 80.76%,
      p = 0.89 [NS]). The pre-operative status of the 2 recipient cohorts differed
      considerably, as indicated by the standard allocation group consisting of 65.8%
      "high-urgency" (HU)-listed patients, whereas the rescue offers were used for only
      11.1% of HU-listed recipients, reflecting our center's policy. CONCLUSIONS:
      Rescue allocation donor lungs can be used safely for transplantation and
      therefore salvaged for the donor pool. The data support our policy of accepting
      marginal donor lungs for stable recipients. This practice leads to very good
      overall survival.

PMID- 23953919
TI  - Dual defibrillation for refractory ventricular fibrillation in a patient with a
      left ventricular assist device.

PMID- 23953920
TI  - Acute antibody-mediated rejection after lung transplantation.
AB  - BACKGROUND: Antibody-mediated rejection (AMR) after lung transplantation remains
      enigmatic, and there is no consensus on the characteristic clinical, immunologic
      and histologic features. METHODS: We performed a retrospective, single-center
      cohort study and identified cases of acute AMR based on the presence of
      circulating donor-specific human leukocyte antigen (HLA) antibodies (DSA),
      histologic evidence of acute lung injury, C4d deposition and clinical allograft
      dysfunction. RESULTS: We identified 21 recipients with acute AMR based on the
      aforementioned criteria. AMR occurred a median 258 days after transplantation; 7
      recipients developed AMR within 45 days of transplantation. All patients had
      clinical allograft dysfunction, DSA, histology of acute lung injury and capillary
      endothelial C4d deposition. Fifteen recipients improved clinically and survived
      to hospital discharge, but 6 died of refractory AMR. One survivor had
      bronchiolitis obliterans syndrome at the time of AMR diagnosis; 13 of the 14
      remaining survivors developed chronic lung allograft dysfunction (CLAD) during
      follow-up. Overall, 15 recipients died during the study period, and the median
      survival after the diagnosis of AMR was 593 days. CONCLUSIONS: Acute AMR can be a
      fulminant form of lung rejection, and survivors are at increased risk of
      developing CLAD. The constellation of acute lung injury, DSA and capillary
      endothelial C4d deposition is compelling for acute AMR in recipients with
      allograft dysfunction. This clinicopathologic definition requires validation in a
      multicenter cohort, but may serve as a foundation for future studies to further
      characterize AMR.

PMID- 23953921
TI  - Identification and characterization of single-stranded DNA-binding protein from
      the facultative psychrophilic bacteria Pseudoalteromonas haloplanktis.
AB  - Single-stranded DNA-binding protein (SSB) plays an important role in DNA
      metabolism such as DNA replication, repair, and recombination, and is essential
      for cell survival. This study reports on the ssb-like gene cloning, gene
      expression and characterization of a single-stranded DNA-binding protein of
      Pseudoalteromonas haloplanktis (PhaSSB) and is the first report of such a protein
      from psychrophilic microorganism. PhaSSB possesses a high sequence similarity to
      Escherichia coli SSB (48% identity and 57% similarity) and has the longest amino
      acid sequence (244 amino acid residues) of all the known bacterial SSBs with one
      OB-fold per monomer. An analysis of purified PhaSSB by means of chemical cross
      linking experiments, sedimentation analysis and size exclusion chromatography
      revealed a stable tetramer in solution. Using EMSA, we characterized the
      stoichiometry of PhaSSB complexed with a series of ssDNA homopolymers, and the
      size of the binding site was determined as being approximately 35 nucleotides
      long. In fluorescence titrations, the occluded site size of PhaSSB on poly(dT) is
      34 nucleotides per tetramer under low-salt conditions (2mM NaCl), but increases
      to 54-64 nucleotides at higher-salt conditions (100-300mM NaCl). This suggests
      that PhaSSB undergoes a transition between ssDNA binding modes, which is observed
      for EcoSSB. The binding properties of PhaSSB investigated using SPR technology
      revealed that the affinity of PhaSSB to ssDNA is typical of SSB proteins. The
      only difference in the binding mode of PhaSSB to ssDNA is a faster association
      phase, when compared to EcoSSB, though compensated by faster dissociation rate.
      When analyzed by differential scanning calorimetry (DSC), the melting temperature
      (Tm) was determined as 63  degrees C, which is only a few degrees lower than for
      EcoSSB.

PMID- 23953922
TI  - The role of epigenetics in hybrid vigour.
AB  - Hybrid vigour, or heterosis, refers to the increased yield and biomass of hybrid
      offspring relative to the parents. Although this has been exploited in plants for
      agriculture and horticulture, the molecular and cellular mechanisms underlying
      hybrid vigour are largely unknown. Genetic analyses show that there are a large
      number of quantitative trait loci (QTLs) that contribute to the heterotic
      phenotype, indicating that it is a complex phenomenon. Gene expression in hybrids
      is regulated by the interactions of the two parental epigenetic systems and the
      underlying genomes. Increasing understanding of the interplay of small RNA (sRNA)
      molecules, DNA methylation, and histone marks provides new opportunities to
      define the basis of hybrid vigour and to understand why F1 heterosis is not
      passed on to subsequent generations. We discuss recent findings that suggest the
      existence of several pathways that alter DNA methylation patterns, which may lead
      to transcriptional changes resulting in the heterotic phenotype. 

PMID- 23953923
TI  - Sex chromosome dosage compensation: definitely not for everyone.
AB  - Sex chromosomes often entail gene dose differences between the sexes, which if
      not compensated for, lead to differences between males and females in the
      expression of sex-linked genes. Recent work has shown that different organisms
      respond to sex chromosome dose in a variety of ways, ranging from complete sex
      chromosome dosage compensation in some species to active compensation of only a
      minority genes in other organisms. Although we still do not understand the
      implications of the diversity in sex chromosome dosage compensation, its
      realization has created exciting new opportunities to study the evolution,
      mechanism, and consequences of gene regulation. However, confusion remains as to
      what sorts of genes are likely to be dosage compensated, how dosage compensation
      evolves, and why complete dosage compensation appears to be limited to male
      heterogametic species. In this review, I survey the status of dosage compensation
      to answer these questions and identify current controversies in this fast-moving
      field. 

PMID- 23953924
TI  - Increasing numbers of citations and higher impact factor in 2012: the British
      Journal of Nutrition continues to show steady improvement.

PMID- 23953925
TI  - Biological responses of juvenile European sea bass (Dicentrarchus labrax) exposed
      to contaminated sediments.
AB  - Multiple anthropogenic activities present along coastal environments may affect
      the health status of aquatic ecosystems. In this study, specimens of European sea
      bass (Dicentrarchus labrax) were exposed for 30 days to highly contaminated
      sediment collected from the industrial area between Augusta and Priolo (Syracuse,
      Italy), defined as the most mercury polluted site in the Mediterranean. The aim
      was to evaluate the responses of juvenile D. labrax to highly contaminated
      sediments, particularly enriched in Hg, in order to enhance the scarce knowledge
      on the potential compensatory mechanisms developed by organisms under severe
      stress conditions. Apoptotic and proliferative activities [cell turnover:
      Proliferating Cell Nuclear Antigen (PCNA) and FAS Ligand (FasL)], onset of
      hypoxic condition [hypoxia: Hypoxia Inducibile Factor-1alpha (HIF-1alpha)], and
      changes in the neuroendocrine control mechanisms [neurotransmission: Tyrosine
      Hydroxylase (TH), Choline Acetyltransferase (ChAT), Acetylcholinesterase (AChE),
      5-Hydroxytryptamine (5-HT) and 5-Hydroxytryptamine receptor 3 (5-HT3)] were
      investigated in sea bass gill tissues. In the specimens exposed to the polluted
      sediment, the occurrence of altered cell turnover may result in impaired gas
      exchange that leads to a condition of "functional hypoxia". Changes in
      neurotransmission pathways were also observed, suggesting a remodeling process as
      an adaptive response to increase the O2-carrying capacity and restore the normal
      physiological conditions of the gills. Overall, these findings demonstrated that
      although chronic exposure to heavy metal polluted sediments alters the
      functioning of both the nervous and endocrine systems, as well as plasticity of
      the gill epithelium, fish are able to trigger a series of physiological
      adjustments or adaptations interfering with specific neuroendocrine control
      mechanisms that enable their long-term survival. 

PMID- 23953926
TI  - Effects of non-steroidal estrogen diethylstilbestrol on pH and ion transport in
      the mantle epithelium of a bivalve Anodonta cygnea.
AB  - Freshwater bivalves are used as sentinel organisms to detect pollutants effects
      in the aquatic environment due to their sedentary nature, filter-feeding
      behaviour. We aimed to determine the in vivo, ex vivo and in vitro influence of
      Diethylstilbestrol (DES), a widely used synthetic non-steroidal estrogen and
      endocrine disruptor, in Anodonta cygnea shell growth mechanisms. For that, in
      vivo exposure to DES (0.75MUM) during 15 days, in vitro and ex vivo exposure of
      outer mantle epithelium (OME) cells to DES (0.75MUM), were performed followed by
      study of short-circuit current (Isc), transepithelial potential (Vt) and
      transepithelial conductance (Gt) as well as identification of membrane transport
      systems and intracellular pH (pHi). Our results show that in vivo exposure to DES
      decreases in 30% the OME Isc and ex vivo addition of DES to the basolateral side
      of OME also induced Isc decrease. Several membrane transporters such as V-type
      ATPases, Na(+)/H(+) exchangers, Na(+)-K(+) pump, Na(+)-driven and Na(+)
      independent HCO3(-)/Cl(-) transporters and Na(+)/HCO3(-) co-transporter were
      identified as responsible for pHi maintenance in OME and noteworthy, DES caused a
      pHi decrease in OME cells similar to the effect observed when OME cells were
      exposed to 4,4'-diisothiocyanostilbene disulfonic acid (DIDS), an inhibitor of
      several bicarbonate membrane transporters. The addition of DIDS after OME cells
      exposure to DES did not cause any alteration. We concluded that DES is able to
      modulate membrane ion transport and pHi in the OME of A. cygnea and that this
      effect seems to be due to inhibition of HCO3(-)/Cl(-) co-transporters present on
      the basolateral membrane. 

PMID- 23953927
TI  - [Pathological calcifications: a medical diagnosis based on their physicochemical
      properties].
AB  - This paper gathers different investigations dedicated to pathological
      calcifications made of apatite in order to define the structural characteristics,
      which display a clinical significance. Such approach helps the clinician to
      define the characterisation tools, which have to be combined to obtain such
      structural characteristics in order to establish a possible relationship between
      the structural characteristics of the pathological calcifications and the
      disease. The fact that it is now possible to perform such experiments at the
      subcellular scale gives new opportunities for a large number of diseases
      associated to pathological calcification. Moreover, new diagnostic tools based on
      these characterisation techniques, quite sensitive to analyze microcrystals, can
      be defined. 

PMID- 23953928
TI  - The role of ghrelin signalling in second-generation antipsychotic-induced weight
      gain.
AB  - Based on clinical and animal studies, this review suggests a tri-phasic effect of
      second-generation antipsychotics (SGAs) on circulating ghrelin levels: an initial
      increase exerted by the acute effect of SGAs; followed by a secondary decrease
      possibly due to the negative feedback from the SGA-induced body weight gain or
      hyperphagia; and a final re-increase to reach the new equilibrium. Moreover, the
      results can also vary depending on individual SGAs, other hormonal states,
      dietary choices, and other confounding factors including medical history, co
      treatments, age, gender, and ghrelin measurement techniques. Interestingly, rats
      treated with olanzapine, an SGA with high weight gain liabilities, are associated
      with increased hypothalamic ghrelin receptor (GHS-R1a) levels. In addition,
      expressions of downstream ghrelin signalling parameters at the hypothalamus,
      including neuropeptide Y (NPY)/agouti-related peptide (AgRP) and
      proopiomelanocortin (POMC) are also altered under SGA treatments. Thus,
      understanding the role of ghrelin signalling in antipsychotic drug-induced weight
      gain should offer potential novel pharmacological targets for tackling the
      obesity side-effect of SGAs and its associated metabolic syndrome.

PMID- 23953930
TI  - Pain education: innovation, scholarship, and evidence.

PMID- 23953931
TI  - Presidential address: annual meeting of the American Academy of Pain Medicine.

PMID- 23953929
TI  - Acute glucocorticoid effects on response inhibition in borderline personality
      disorder.
AB  - INTRODUCTION: Growing evidence suggests inhibition dysfunctions in borderline
      personality disorder (BPD). Moreover, abnormalities in hypothalamic-pituitary
      adrenal (HPA) axis functioning have also been found in BPD patients. In healthy
      individuals, response inhibition has been sensitive to acute stress, and previous
      research indicates that effects mediated by the HPA axis become particularly
      apparent when emotional stimuli are processed. This study aimed to explore the
      influence of acute hydrocortisone administration on response inhibition of
      emotional stimuli in BPD patients compared to healthy control participants.
      METHODS: After a single administration of 10mg hydrocortisone or placebo, 32
      female BPD patients and 32 healthy female participants performed an adapted
      emotional go/no-go paradigm to assess response inhibition for emotional face
      stimuli in a cross-over study. RESULTS: Acute cortisol elevations decreased the
      reaction times to target stimuli in both BPD patients and healthy controls.
      Patients and controls did not differ in task performance; however, BPD patients
      with comorbid posttraumatic stress disorder (PTSD) displayed longer reaction
      times than patients without PTSD. In contrast, the occurrence of comorbid eating
      disorder had no significant impact on go/no-go performance. No significant
      interaction effect between the treatment condition and the emotional valence of
      the face stimuli was found. CONCLUSIONS: Acute hydrocortisone administration
      enhances response inhibition of face stimuli in BPD patients and healthy
      controls, regardless of their emotional valence. Our results agree with the
      suggestion that moderate cortisol enhancement increases the inhibition of task
      irrelevant distracters.

PMID- 23953933
TI  - Interplays between ATM/Tel1 and ATR/Mec1 in sensing and signaling DNA double
      strand breaks.
AB  - DNA double-strand breaks (DSBs) are highly hazardous for genome integrity because
      they have the potential to cause mutations, chromosomal rearrangements and
      genomic instability. The cellular response to DSBs is orchestrated by signal
      transduction pathways, known as DNA damage checkpoints, which are conserved from
      yeasts to humans. These pathways can sense DNA damage and transduce this
      information to specific cellular targets, which in turn regulate cell cycle
      transitions and DNA repair. The mammalian protein kinases ATM and ATR, as well as
      their budding yeast corresponding orthologs Tel1 and Mec1, act as master
      regulators of the checkpoint response to DSBs. Here, we review the early steps of
      DSB processing and the role of DNA-end structures in activating ATM/Tel1 and
      ATR/Mec1 in an orderly and reciprocal manner. 

PMID- 23953934
TI  - Beneficial effects of silibinin against the progression of metabolic syndrome,
      increased oxidative stress, and liver steatosis in Psammomys obesus, a relevant
      animal model of human obesity and diabetes.
AB  - BACKGROUND: Insulin resistance and oxidative stress are major pathogenic
      mechanisms leading to chronic liver diseases in diabetic subjects. The gerbil
      Psammomys obesus is a unique model of nutritional diabetes resembling the disease
      in humans. This study investigated whether the natural ingredient silibinin,
      known as hepatoprotective, could decrease oxidative stress and reduce liver
      damage in obese gerbils. METHODS: Control animals were fed their vegetable-based
      low caloric diet while two other rat groups ingested a high calorie diet for 14
      weeks. Silibinin, or its vehicle, was administrated by gastric intubation (100
      mg/kg per day) from the 7th week of treatment, which corresponds to an
      established insulin resistance state. At the end of the experiments, the hepatic
      biochemical profile, markers of oxidative stress in either plasma or liver
      tissue, and histological alterations were examined. RESULTS: Diabetic P. obesus
      displayed many metabolic disturbances (hyperinsulinemia, hyperglycemia,
      dyslipidemia), which were aggravated for the last 8 weeks. These events were
      coupled with greater oxidative stress (decline in glutathione, rise in
      lipoperoxidation). In addition, glutathione peroxidase activity was reduced while
      the level of superoxide dismutase was elevated. Interestingly, treatment with
      silibinin alleviated most of the metabolic defects, especially high triglyceride
      levels, reduced insulin resistance and largely restored antioxidant status. Also,
      Masson's trichrome staining revealed distinct steatosis, yet silibinin partially
      reversed this manifestation. CONCLUSION: Silibinin affords substantial protection
      against the progression of insulin resistance in Type 2 diabetes mellitus for P.
      obesus by hampering the oxidative process and improving hepatic metabolism.

PMID- 23953935
TI  - Patient information ahead of thyroid surgery. Guidelines of the French Society of
      Oto-Rhino-Laryngology and Head and Neck Surgery (SFORL).
AB  - OBJECTIVE: The authors present the guidelines of the French Society of Oto-Rhino
      Laryngology and Head and Neck Surgery (SFORL) on patient information ahead of
      thyroid surgery. METHODS: A multidisciplinary medical team was tasked with a
      scientific literature review on this topic. The texts retrieved were analyzed by
      an independent committee. A joint meeting drew up the final guidelines. The
      strength of the recommendations (grade A, B or C) was based on levels of
      evidence. RESULTS: It is recommended that the results of preoperative exploration
      and the indications for surgery should be explained to the patient. Patients
      should be informed as to the type of surgery, surgical objectives, risks and
      consequences. It is mandatory to obtain the patient's written consent before
      surgery. CONCLUSION: Appropriate medical information is a critical step in
      patient management.

PMID- 23953936
TI  - Cystic lesions of the pterygoid process.
AB  - INTRODUCTION: Cystic lesions of the pterygoid process are rare: there are only
      four case reports in PubMed. CASE REPORT: Two new cases (one schwannoma and one
      cystic lymphangioma) are reported, with clinical, radiological and therapeutic
      aspects. DISCUSSION: A literature review presents the semiology, radiology and
      treatment of cystic lesions of the pterygoid process.

PMID- 23953937
TI  - Hibernoma presenting as an asymptomatic neck mass.
AB  - BACKGROUND: Hibernomas are rare benign tumors of brown fat tissue origin. These
      tumors are generally found in locations where fetal fat persists (back, axilla,
      thorax and retroperitoneum). METHODS AND RESULTS: We report a case of a patient
      with an asymptomatic neck mass that initially presented for evaluation of
      hoarseness. Imaging and complete surgical excision of the mass were performed and
      revealed hibernoma. Review of the literature for the presentation of hibernoma in
      the neck is performed. CONCLUSION: Hibernomas are rare benign tumors that
      infrequently present in the neck. Complete surgical removal is curative. To date
      no malignant transformation or metastasis has been described.

PMID- 23953938
TI  - Brainstem auditory evoked potentials with the use of acoustic clicks and complex
      verbal sounds in young adults with learning disabilities.
AB  - PURPOSE AND BACKGROUND: Acoustic signals are transmitted through the external and
      middle ear mechanically to the cochlea where they are transduced into electrical
      impulse for further transmission via the auditory nerve. The auditory nerve
      encodes the acoustic sounds that are conveyed to the auditory brainstem. Multiple
      brainstem nuclei, the cochlea, the midbrain, the thalamus, and the cortex
      constitute the central auditory system. In clinical practice, auditory brainstem
      responses (ABRs) to simple stimuli such as click or tones are widely used.
      Recently, complex stimuli or complex auditory brain responses (cABRs), such as
      monosyllabic speech stimuli and music, are being used as a tool to study the
      brainstem processing of speech sounds. We have used the classic 'click' as well
      as, for the first time, the artificial successive complex stimuli 'ba', which
      constitutes the Greek word 'baba' corresponding to the English 'daddy'. PATIENTS
      AND METHODS: Twenty young adults institutionally diagnosed as dyslexic (10
      subjects) or light dyslexic (10 subjects) comprised the diseased group. Twenty
      sex-, age-, education-, hearing sensitivity-, and IQ-matched normal subjects
      comprised the control group. Measurements included the absolute latencies of
      waves I through V, the interpeak latencies elicited by the classical acoustic
      click, the negative peak latencies of A and C waves, as well as the interpeak
      latencies of A-C elicited by the verbal stimulus 'baba' created on a digital
      speech synthesizer. RESULTS: The absolute peak latencies of waves I, III, and V
      in response to monoaural rarefaction clicks as well as the interpeak latencies I
      III, III-V, and I-V in the dyslexic subjects, although increased in comparison
      with normal subjects, did not reach the level of a significant difference
      (p<0.05). However, the absolute peak latencies of the negative wave C and the
      interpeak latencies of A-C elicited by verbal stimuli were found to be increased
      in the dyslexic group in comparison with the control group (p=0.0004 and p=0.045,
      respectively). In the subgroup consisting of 10 patients suffering from 'other
      learning disabilities' and who were characterized as with 'light' dyslexia
      according to dyslexia tests, no significant delays were found in peak latencies A
      and C and interpeak latencies A-C in comparison with the control group.
      CONCLUSIONS: Acoustic representation of a speech sound and, in particular, the
      disyllabic word 'baba' was found to be abnormal, as low as the auditory
      brainstem. Because ABRs mature in early life, this can help to identify subjects
      with acoustically based learning problems and apply early intervention,
      rehabilitation, and treatment. Further studies and more experience with more
      patients and pathological conditions such as plasticity of the auditory system,
      cochlear implants, hearing aids, presbycusis, or acoustic neuropathy are
      necessary until this type of testing is ready for clinical application.

PMID- 23953939
TI  - Thought-based interaction with the physical world.
AB  - Operating a brain-computer interface (BCI) is a skill that individuals must
      learn. A recent study demonstrated that successful skill acquisition enables
      human individuals to control telepresence robotic devices in three-dimensional
      physical space using the non-invasive electroencephalogram (EEG). Although the
      results are very promising, there is room for improvement in the future. 

PMID- 23953940
TI  - Anti-hepatitis C virus antibody detection in oral fluid: influence of human
      immunodeficiency virus co-infection.
AB  - BACKGROUND: Saliva sampling may provide an easier access to hepatitis C virus
      (HCV) screening test. HIV infection influence on specific salivary antibody
      detection has not been extensively studied. OBJECTIVES: An anti-HCV antibodies
      (HCV-Ab) test was adapted for saliva specimens and its performances were analysed
      according to the patients' HIV status and related factors such as CD4 cell counts
      and HIV viral load. METHODS: Four patients groups were selected: (i) HCV and HIV
      negative volunteers (n=28); (ii) HCV positive and HIV negative patients (n=30);
      (iii) HCV negative and HIV positive patients (n=30); (iv) HCV and HIV co-infected
      patients (n=30). Saliva samples were collected (Salivette system, Sarstedt) and
      an in-house adapted HCV-Ab detection assay was performed (MONOLISA anti-HCV PLUS
      Version 2, Biorad). HIV viral load, CD4 cells counts and HCV viremic status were
      reported. RESULTS: Sensitivity and specificity of saliva anti-HCV antibody tests
      in the HIV negative groups were 90% and 100%, respectively, compared to 73% and
      93%, respectively in the HIV infected population. Compared to the HIV negative
      population, HIV mono-infected patients presented higher absorbance values
      (p=0.01) and HIV/HCV co-infected population presented lower HCV-Ab absorbance
      values (p<0.001). Sensitivity decline was associated with HIV replication
      (p=0.02), HCV replication (p=0.16) but not with CD4 cell counts (p=0.64).
      CONCLUSION: Performances of salivary HCV antibodies testing are strongly
      deteriorated in the HIV positive population, especially for patients with
      residual HIV replication. This serious limitation should prompt careful testing
      of non-invasive screening tests for hepatitis C in HIV-infected patients before
      use in real screening conditions.

PMID- 23953942
TI  - Risk of suicidal behavior in medical-surgical settings.

PMID- 23953941
TI  - Finding those at risk: acute HIV infection in Newark, NJ.
AB  - BACKGROUND: A screening strategy combining rapid HIV-1/2 (HIV) antibody testing
      with pooled HIV-1 RNA testing increases identification of HIV infections, but may
      have other limitations that restrict its usefulness to all but the highest
      incidence populations. OBJECTIVE: By combining rapid antibody detection and
      pooled nucleic acid amplification testing (NAAT) testing, we sought to improve
      detection of early HIV-1 infections in an urban Newark, NJ hospital setting.
      STUDY DESIGN: Pooled NAAT HIV-1 RNA testing was offered to emergency department
      patients and outpatients being screened for HIV antibodies by fingerstick-rapid
      HIV testing. For those negative by rapid HIV and agreeing to NAAT testing, pooled
      plasma samples were prepared and sent to the University of Washington where real
      time reverse transcription-polymerase chain reaction (RT-PCR) amplification was
      performed. RESULTS: Of 13,226 individuals screened, 6381 had rapid antibody
      testing alone, and 6845 agreed to add NAAT HIV screening. Rapid testing
      identified 115 antibody positive individuals. Pooled NAAT increased HIV-1 case
      detection by 7.0% identifying 8 additional cases. Overall, acute HIV infection
      yield was 0.12%. While males represent only 48.1% of those tested by NAAT, all
      samples that screened positive for HIV-1 RNA were obtained from men. CONCLUSION:
      HIV-1 RNA testing of pooled, HIV antibody-negative specimens permits
      identification of recent infections. In Newark, pooled NAAT increased HIV-1 case
      detection and provided an opportunity to focus on treatment and prevention
      messages for those most at risk of transmitting infection. Although constrained
      by client willingness to participate in testing associated with a need to return
      to receive further results, use of pooled NAAT improved early infection
      sensitivity.

PMID- 23953943
TI  - Dynamic response to peripheral nerve injury detected by in situ hybridization of
      IL-6 and its receptor mRNAs in the dorsal root ganglia is not strictly correlated
      with signs of neuropathic pain.
AB  - BACKGROUND: IL-6 is a typical injury-induced mediator. Together with its
      receptors, IL-6 contributes to both induction and maintenance of neuropathic pain
      deriving from changes in activity of primary sensory neurons in dorsal root
      ganglia (DRG). We used in situ hybridization to provide evidence of IL-6 and IL-6
      receptors (IL-6R and gp130) synthesis in DRG along the neuraxis after unilateral
      chronic constriction injury (CCI) of the sciatic nerve as an experimental model
      of neuropathic pain. RESULTS: All rats operated upon to create unilateral CCI
      displayed mechanical allodynia and thermal hyperalgesia in ipsilateral hind paws.
      Contralateral hind paws and forepaws of both sides exhibited only temporal and
      nonsignificant changes of sensitivity. Very low levels of IL-6 and IL-6R mRNAs
      were detected in naive DRG. IL-6 mRNA was bilaterally increased not only in DRG
      neurons but also in satellite glial cells (SGC) activated by unilateral CCI. In
      addition to IL-6 mRNA, substantial increase of IL-6R mRNA expression occurred in
      DRG neurons and SGC following CCI, while the level of gp130 mRNA remained similar
      to that of DRG from naive rats. CONCLUSIONS: Here we evidence for the first time
      increased synthesis of IL-6 and IL-6R in remote cervical DRG nonassociated with
      the nerve injury. Our results suggest that unilateral CCI of the sciatic nerve
      induced not only bilateral elevation of IL-6 and IL-6R mRNAs in L4-L5 DRG but
      also their propagation along the neuraxis to remote cervical DRG as a general
      neuroinflammatory reaction of the nervous system to local nerve injury without
      correlation with signs of neuropathic pain. Possible functional involvement of IL
      6 signaling is discussed.

PMID- 23953945
TI  - The global perspective on neurology training: the World Federation of Neurology
      survey.
AB  - This World Federation of Neurology (WFN) study aimed to characterize the status
      quo of post-graduate neurology training throughout the world and enable a better
      orientation on global training in neurology. Basic data on training curricula and
      working conditions of neurology residents and neurologists in 39 countries
      worldwide were evaluated. Our data show considerable differences in manpower and
      training, but a continuous improvement within the last 10 years of observation.
      Worldwide a spread of interim evaluations and final examinations of different
      types are used. Online resources will undoubtedly profoundly change skill and
      knowledge acquisition and training practices in Neurology in the coming years.

PMID- 23953944
TI  - Experimental evidence for the use of CCR2 antagonists in the treatment of type 2
      diabetes.
AB  - OBJECTIVE: CCR2 inhibition has produced promising experimental and clinical anti
      hyperglycemic effects. These results support the thesis that insulin resistance
      and Type 2 diabetes (T2D) are associated with chronic unresolved inflammation.
      The aim of this study was to provide a broad analysis of the various
      physiological changes occurring in mouse models of T2D in connection with
      pharmacological CCR2 inhibition. MATERIALS/METHODS: A mouse-active chemical
      analogue of the clinical candidate CCX140-B was tested in diet-induced obese
      (DIO) mice and db/db mice. Measurements included: adipose tissue inflammatory
      macrophage counts; peripheral blood glucose levels at steady-state and after
      glucose and insulin challenges; peripheral blood insulin and adiponectin levels;
      24-h urine output and urinary glucose levels; pancreatic islet number and size;
      hepatic triglyceride and glycogen content; and hepatic glucose-6-phosphatase
      levels. RESULTS: In DIO mice, the CCR2 antagonist completely blocked the
      recruitment of inflammatory macrophages to visceral adipose tissue. The mice
      exhibited reduced hyperglycemia and insulinemia, improved insulin sensitivity,
      increased circulating adiponectin levels, decreased pancreatic islet size and
      increased islet number. It also reduced urine output, glucose excretion, hepatic
      glycogen and triglyceride content and glucose 6-phosphatase levels. Similar
      effects were observed in the db/db diabetic mice. CONCLUSIONS: These data
      indicate that pharmacological inhibition of CCR2 in models of T2D can reduce
      inflammation in adipose tissue, alter hepatic metabolism and ameliorate multiple
      diabetic parameters. These mechanisms may contribute to the promising anti
      diabetic effects seen in humans with at least one CCR2 antagonist.

PMID- 23953946
TI  - Post-intervention TCD examination may be useful to predict outcome in acute
      ischemic stroke patients with successful intra-arterial intervention.
AB  - BACKGROUND AND PURPOSE: Some acute stoke patients have a poor outcome despite
      successful arterial recanalization. We hypothesized that transcranial Doppler
      (TCD) findings from the rescued artery might predict poor outcome in patients
      with recanalization. METHODS: Acute stroke patients treated with internal carotid
      artery or middle cerebral artery (MCA) occlusions with follow-up TCD examination
      after intra-arterial (IA) intervention were retrospectively analyzed. Only
      patients with at least a Thrombolysis In Myocardial Infarction (TIMI) flow grade
      >= 2 in the MCA territory were included. Mean flow velocity (MFV) and pulsatility
      index (PI) of the rescued MCA were obtained by TCD. Poor clinical outcome was
      defined as in-hospital death or decompressive craniectomy. RESULTS: Among 50
      patients, there were 8 (16%) in the Poor Outcome group and 42 (84%) in the Non
      poor Outcome group. TCD was conducted at a median of 1 day (interquartile range,
      1-1) after IA therapy. Although MCA MFV was not different between the two groups,
      MCA PI was significantly higher in the Poor Outcome group than in the Non-poor
      Outcome group (1.3 [1.1-1.7] vs. 0.8 [0.7-1.1], p = 0.002). After adjusting for
      the National Institutes of Health Stroke Scale score on admission, the Alberta
      Stroke Programme Early Computed Tomography score, a past history of coronary
      artery disease and the Thrombolysis In Brain Ischemia grade, MCA PI was an
      independent predictor of poor outcome (odds ratio: 1.71, 95% confidence interval:
      1.10-2.66, p = 0.017). CONCLUSION: Follow-up TCD examination after IA
      intervention in acute stroke patients may predict poor outcome beyond
      angiographic residual TIMI flow.

PMID- 23953947
TI  - A recurrent longitudinally extensive transverse myelitis with Aquaporin-4(AQP4)
      antibody after herpes zoster.
AB  - Longitudinally extensive transverse myelitis (LETM) is a syndrome that involves
      three or more vertebral segments in the spinal cord lesion, and it is one of the
      characteristic features of neuromyelitis optica (NMO) differentiating it from
      multiple sclerosis. Many studies proved the importance of aquaporin-4 (AQP4)
      antibody, which plays a vital role in the pathogenesis of NMO. Recent reports
      suggest that recurrent LETM patients with positive anti-AQP4 antibody titers have
      a higher chance of converting to NMO, and they are now termed as NMO spectrum
      disorders (NMOSD). The specific role of AQP4 antibody in NMO is yet to be
      elucidated but there are reports to bring up the pathogenesis in relation with
      infectious events. Interestingly, parainfectious NMOSD tends to spare the optic
      nerve unlike classic NMOSD. Here we report a young woman who was once diagnosed
      as herpes zoster-related LETM, but later developed as recurrent LETM with
      positive AQP4 antibody titers, which renders the diagnosis of parainfectious LETM
      without optic neuritis. 

PMID- 23953948
TI  - Comparisons of polydrug use at national and inner city levels in England:
      associations with demographic and socioeconomic factors.
AB  - PURPOSE: This study compares polydrug use in national and inner city samples to
      (1) examine patterns of use underlying different prevalence rates and (2)
      identify how inner city polydrug use needs targeting in ways not suggested by
      national research. METHODS: Latent class analyses on indicators of illicit drug
      use in the last year, hazardous alcohol use, and cigarette smoking were compared
      between the inner city 2008-2010 South East London Community Health study (n =
      1698) and the nationally representative 2007 Adult Psychiatric Morbidity Survey
      in England (n = 7403). Multinomial logistic regressions then examined latent
      class solutions with demographic and socioeconomic factors. RESULTS: Both samples
      revealed three notably similar classes of polydrug users: a "high-drug" group
      using multiple substances; a "moderate-drug" group using cannabis, alcohol, and
      cigarettes; and a "low-drug" group reporting minimal alcohol and cigarette use.
      However, South East London Community Health reported lower risks of polydrug use
      for ethnic minorities but not for more educated participants. CONCLUSIONS:
      Despite higher polydrug use prevalence in the inner city, latent classes of
      polydrug users were similar between samples. Some demographic and socioeconomic
      factors differed between the samples, suggesting the need for inner city services
      to use both local and national data for policy planning.

PMID- 23953949
TI  - Comment on: "Laparoscopic sleeve gastrectomy compared to other bariatric surgical
      procedures: a systematic review of randomized trials".

PMID- 23953950
TI  - The challenge of treating spikes.

PMID- 23953951
TI  - The babkin reflex in infants: clinical significance and neural mechanism.
AB  - BACKGROUND: There have been very few studies concerning the Babkin reflex-opening
      of the mouth and flexion of the arms in response to stimulation of the palms. We
      attempted to clarify the clinical significance and neural mechanism of the reflex
      through systematic review. METHODS: Searches were conducted on Medline, Embase,
      and Google Scholar from their inception through August 2012. RESULTS: In normal
      term infants, the Babkin reflex can be elicited from the time of birth, becomes
      increasingly suppressed with age, and disappears in the great majority by the end
      of the fifth month of age. A marked response in the fourth or fifth month of age
      and persistence of the reflex beyond the fifth month of age are generally
      regarded as abnormal. On the other hand, because there are some normal infants
      showing no response during the neonatal period or early infancy, the absence of
      the response during these periods is not necessarily an abnormal finding.
      CONCLUSIONS: Infants with these abnormal findings should be carefully observed
      for the appearance of neurological abnormalities including cerebral palsy and
      mental retardation. It is most likely that the Babkin reflex is mediated by the
      reticular formation of the brainstem, which receives inputs from the nonprimary
      motor cortices. On the basis of the hand-mouth reflex, more adaptive movement
      develops as control of the nonprimary motor cortices over the reflex mechanism in
      the reticular formation increases. Soon it evolves into the voluntary eye-hand
      mouth coordination necessary for food intake as the control of the prefrontal
      cortex over the nonprimary motor cortices becomes predominant.

PMID- 23953952
TI  - National variation in costs and mortality for leukodystrophy patients in US
      children's hospitals.
AB  - BACKGROUND: Inherited leukodystrophies are progressive, debilitating neurological
      disorders with few treatment options and high mortality rates. Our objective was
      to determine national variation in the costs for leukodystrophy patients and to
      evaluate differences in their care. METHODS: We developed an algorithm to
      identify inherited leukodystrophy patients in deidentified data sets using a
      recursive tree model based on International Classification of Disease, 9th
      Edition, Clinical Modification, diagnosis and procedure charge codes. Validation
      of the algorithm was performed independently at two institutions, and with data
      from the Pediatric Health Information System (PHIS) of 43 US children's
      hospitals, for a 7-year period between 2004 and 2010. RESULTS: A recursive
      algorithm was developed and validated, based on six International Classification
      of Disease, 9th Edition, Clinical Modification, codes and one procedure code that
      had a sensitivity up to 90% (range 61-90%) and a specificity up to 99% (range 53
      99%) for identifying inherited leukodystrophy patients. Inherited leukodystrophy
      patients comprise 0.4% of admissions to children's hospitals and 0.7% of costs.
      During 7 years, these patients required $411 million of hospital care, or
      $131,000/patient. Hospital costs for leukodystrophy patients varied at different
      institutions, ranging from two to 15 times more than the average pediatric
      patient. There was a statistically significant correlation between higher volume
      and increased cost efficiency. Increased mortality rates had an inverse
      relationship with increased patient volume that was not statistically
      significant. CONCLUSIONS: We developed and validated a code-based algorithm for
      identifying leukodystrophy patients in deidentified national datasets.
      Leukodystrophy patients account for $59 million of costs yearly at children's
      hospitals. Our data highlight potential to reduce unwarranted variability and
      improve patient care.

PMID- 23953953
TI  - Long-term response to high-dose diazepam treatment in continuous spikes and waves
      during sleep.
AB  - BACKGROUND: This study evaluated whether the reduction in epileptiform activity
      after treatment with high-dose diazepam in continuous spikes and waves during
      sleep persists over time. PATIENTS: Patients aged 1 to 21 years with continuous
      spikes and waves during sleep who received high-dose nocturnal diazepam and who
      had electroencephalogram follow-up were included. Twenty-nine patients met the
      inclusion criteria and underwent a total of 48 high-dose diazepam treatment
      cycles. RESULTS: An overnight reduction of the spike wave percentage of at least
      25% (i.e., 75-50%) occurred in 29 cycles (20 patients), and persisted within 6
      months in 16 of 29 cycles (12 patients), but returned to baseline in three of 29
      cycles (three patients). An overnight reduction of at least 50% (i.e., 75-25%)
      occurred in 15 cycles (13 patients), and persisted within 6 months in eight of 15
      cycles (eight patients), but returned to baseline in three cycles (three
      patients). Twenty of 29 cycles that responded in the short term had persistent
      response on follow-up. Thirteen cycles of treatment were associated with mild
      side effects that did not recur with repeated treatment cycles. CONCLUSIONS:
      Treatment with high-dose diazepam reduced epileptiform activity in continuous
      spikes and waves during sleep in the short term, and improvement persisted for
      several months in most cycles. Short-term response predicted persistence of this
      effect on subsequent follow-up.

PMID- 23953954
TI  - One load to rule them all: mechanical control of the musculoskeletal system in
      development and aging.
AB  - The musculoskeletal system functions because of the precise and coordinated
      assembly of its components, namely bones and joints, muscles, tendons and
      ligaments. This coordination requires cross-talk between the tissues, which is
      mediated by various molecular and mechanical cues. In this review, we summarize
      the progress that has been made in understanding the involvement of mechanical
      loads exerted by the musculature in the development of skeletal and tendinous
      tissues, in their integration into one functional unit and in the maintenance of
      this system. In addition, we discuss the possible role of muscle load in aging
      and propose new directions for future studies of the musculoskeletal system. 

PMID- 23953955
TI  - Inadequacy of vitamins and minerals among high-school pupils in Ouarzazate,
      Morocco.
AB  - OBJECTIVE: To assess micronutrient intakes and the prevalence of inadequacy in a
      sample of high-school pupils in Ouarzazate, Morocco. DESIGN: Food records were
      compiled over three non-consecutive days by pre-trained pupils. Micronutrient
      intakes were estimated using the DIAL software, adapted to include foods commonly
      eaten in Morocco. The prevalence of inadequacy was estimated by the proportion of
      individuals with intakes below the Estimated Average Requirement (EAR) for
      vitamins B12, A and K, thiamin, riboflavin, niacin, pyridoxine, folate, ascorbic
      acid, iodine, Ca, Mg and P; below the Adequate Intake (AI) level for pantothenic
      acid, biotin, Na and K; and using the probability approach for Fe. Data were
      adjusted for intra-individual variation with exclusion of under-reporters.
      SETTING: Ouarzazate, a semi-urban region situated on the southern slopes of the
      High Atlas with little industrial development but an important tourism sector.
      SUBJECTS: A self-selected sample of 312 pupils aged 15-19 years from the five
      public high schools. After exclusion of under-reporters, 293 remained for
      analysis. RESULTS: The highest proportions of below-EAR/AI intakes were seen for
      pantothenic acid (girls 85.1 %, boys 78.0 %), biotin (boys 83.1 %, girls 79.4 %),
      thiamin (boys 66.9 %), folate (girls 93.1 %, boys 74.6 %), iodine (boys 94.9 %,
      girls 88.0 %) and Ca (girls 83.4 %, boys 74.6 %). Na intake was generally in
      excess whereas K intake was below the AI level. In general, girls had better
      quality diets than boys, who appeared to consume more 'empty calories'.
      CONCLUSIONS: Our findings suggest that in this population of Moroccan
      adolescents, nutritional intervention and educational strategies are needed to
      promote healthy eating habits and correct micronutrient inadequacies. To provide
      reliable and precise estimates of nutrient intakes, an update of Moroccan food
      composition databases is urgently needed. We recommend that national authorities
      address these issues.

PMID- 23953956
TI  - Factor analysis in predominantly severe COPD: identification of disease
      heterogeneity by easily measurable characteristics.
AB  - BACKGROUND: The clinical and demographic variables defining the heterogeneity of
      chronic obstructive pulmonary disease (COPD) are unclear. A post-hoc analysis of
      five randomised studies in patients with a history of previous exacerbations
      examined the clinical and demographic characteristics describing moderate-to-very
      severe COPD. METHODS: Factor analysis was performed on all continuous baseline
      demographic and clinical data, without variable selection. Analyses were based on
      the full cohort and on stratifications by pack-years smoked, smoking status,
      gender, and comorbidities; patient exacerbation history was analysed in two of
      the five studies. FINDINGS: 6162 COPD patients were evaluated (70% male; 40%
      current smokers; mean pre-bronchodilator forced expiratory volume in 1 s [FEV1]
      35.2% predicted). Baseline clinical and demographic variables loaded
      differentially on six factors with minimal overlap, explaining 60.4% of the
      heterogeneity: 1) symptoms (cough, dyspnoea, sleep disturbance), health status,
      reliever use; 2) pre-bronchodilator FEV1, FEV1/forced vital capacity, morning
      peak expiratory flow (PEF), body mass index (BMI); 3) blood pressure; 4) age,
      months since first COPD symptoms; 5) PEF variability; 6) pulse, FEV1
      reversibility. Most factors loaded similarly in stratified and exacerbation
      analyses. BMI loaded with reversibility in females, and with age and months since
      first COPD symptoms in ex-smokers. Exacerbations loaded to factor 6.
      INTERPRETATION: Readily available data can explain ~ 60% of COPD heterogeneity in
      a large dataset of predominantly severe COPD patients. Factors were robust over
      determinants of disease outcome; gender, smoking status, pack-years smoked, and
      comorbidities. The main factors were largely unchanged by adding exacerbations.
      Only BMI loaded to other factors.

PMID- 23953957
TI  - Nasal flow, volumes, and minimal cross sectional areas in asthmatics.
AB  - BACKGROUND: The Unified Airways hypothesis suggests an involvement of the upper
      airways in asthma. Critical parameters of the nasal airway can be quantified
      objectively with acoustic rhinometry (AR) and peak nasal inspiratory flow (PNIF).
      OBJECTIVE: We aimed to investigate nasal airway patency in asthmatics compared to
      non-asthmatic controls. Nasal volume, cross sectional area and flow were measured
      using acoustic rhinometry (AR) and peak nasal inspiratory flow (PNIF) in 87
      asthmatics and 93 non-asthmatic controls before and after decongestion with
      xylometazoline. Nasal congestion index (NCI) was calculated, and allergy status
      was assessed by skin prick test or specific IgE. RESULTS: We found significantly
      smaller minimum cross sectional area and nasal cavity volume in asthmatics than
      controls, and the cross sectional area is at its minimum at 2-3 cm from the nasal
      orifice in both groups. AR and PNIF measurements are not different in allergic
      and non allergic subjects in either group. The effect of xylometazoline is not
      significantly different between the 2 groups with regard to AR, but there is a
      significant improvement in PNIF for the asthmatics when assessed by the NCI.
      CONCLUSION: The present study demonstrates a significantly smaller nasal airway
      when assessed by minimum cross sectional area and nasal cavity volume in
      asthmatics than controls, and these findings apply to asthmatics and controls
      irrespective of allergy status.

PMID- 23953958
TI  - Impact of climate change in the epidemiology of vector-borne diseases in domestic
      carnivores.
AB  - Vector-borne diseases are medically important in humans and animals but were long
      considered tropical and known to first affect production animals. This is no
      longer true and we can see today that they are common in domestic animals and
      that they are also present in temperate countries, especially in Europe. In
      recent years, an increase in the diagnosis of vector borne diseases among humans
      and animals has been observed, which may partly due to the development of
      diagnostic tools. Their study requires exchanges and collaborations between the
      many actors involved, especially since the epidemiology seems to be constantly
      evolving. The veterinary practitioner is the first one to notice the emergence of
      cases and to implement prevention measures. He also acts as a sentinel to alert
      epidemiologists. Many factors can explain the epidemiological changes, i.e. all
      human factors, such as the increase in commercial transportation, but also owners
      traveling with their pet during the holidays, the development of "outdoor"
      activities, the increase of individual housings with gardens; to these human
      factors must be added the ignorance of the risks, linked to animals in general
      and to wildlife in particular; then the environmental changes: forest
      fragmentation, establishment of parks; the increase of wild mammal populations
      (deer, carnivores, rodents, etc.); finally, climate changes. Climate change is a
      reality which may explain the increase of density of arthropod vectors, but also
      of their hosts, changes in periods of activity and variations in geographical
      distribution. The authors show the proof of the climate modifications and then
      explain how it has an impact in Europe on ticks, mosquitoes, sandflies and even
      fleas. They conclude on the practical consequences for veterinary practitioners,
      especially with the diagnosis of parasitic diseases or diseases in areas where
      they usually do not occur. However, not any epidemiological modification should
      be linked to climate change, since many other factors are involved and often even
      overriding. 

PMID- 23953959
TI  - Application of probabilistic and fuzzy cognitive approaches in semantic web
      framework for medical decision support.
AB  - This study aimed to focus on medical knowledge representation and reasoning using
      the probabilistic and fuzzy influence processes, implemented in the semantic web,
      for decision support tasks. Bayesian belief networks (BBNs) and fuzzy cognitive
      maps (FCMs), as dynamic influence graphs, were applied to handle the task of
      medical knowledge formalization for decision support. In order to perform
      reasoning on these knowledge models, a general purpose reasoning engine, EYE,
      with the necessary plug-ins was developed in the semantic web. The two formal
      approaches constitute the proposed decision support system (DSS) aiming to
      recognize the appropriate guidelines of a medical problem, and to propose easily
      understandable course of actions to guide the practitioners. The urinary tract
      infection (UTI) problem was selected as the proof-of-concept example to examine
      the proposed formalization techniques implemented in the semantic web. The
      medical guidelines for UTI treatment were formalized into BBN and FCM knowledge
      models. To assess the formal models' performance, 55 patient cases were extracted
      from a database and analyzed. The results showed that the suggested approaches
      formalized medical knowledge efficiently in the semantic web, and gave a front
      end decision on antibiotics' suggestion for UTI. 

PMID- 23953960
TI  - Women's knowledge of abortion law and availability of services in Nepal.
AB  - This paper assesses women's awareness of the liberalization of abortion law and
      their knowledge of a place for obtaining abortion services in Nepal. The data are
      from the 2011 Nepal Demographic and Health Survey. The results are compared with
      data from a similar survey conducted in 2006. Variations in the two measures
      among several population sub-groups are analysed by performing logistic
      regression. Among women aged 15-44, 38.7% (CI: 37.8, 39.6) were aware of the
      legal status of abortion and 59.8% (CI: 58.9, 60.7) knew of a place to have an
      abortion. The percentages of both measures varied considerably by various
      population sub-groups. Over a 5-year period, knowledge of the legality of
      abortion increased by 6.4 percentage points, and awareness of service delivery
      sites increased by 3.3 percentage points. The increases in both measures were,
      however, largely limited to higher wealth quintiles and those with higher
      educational attainment. The results suggest the need to intensify efforts to
      educate women in Nepal, particularly the most disadvantaged women, about abortion
      law, including the conditions under which abortion is permitted, and where to
      access safe abortion services.

PMID- 23953961
TI  - High Activity Arthroplasty Score has a lower ceiling effect than standard scores
      after knee arthroplasty.
AB  - The tested hypothesis was following: the High Activity Arthroplasty Score has a
      significant lower ceiling effect than American Knee Society Score and Oxford Knee
      Score after total knee arthroplasty. One hundred patients operated on for total
      knee arthroplasty with more than one-year follow-up have been included. The
      ceiling effect was 53% for the American Knee Society Score, 33% for the Oxford
      Knee Score, and 0% for the High Activity Arthroplasty Score. High Activity
      Arthroplasty Score had a significantly lower ceiling effect than American Knee
      Society Score and Oxford Knee Score. High Activity Arthroplasty Score has the
      potential to detect more subtle differences in level of function than standard
      scoring systems among a non-selected total knee arthroplasty population. 

PMID- 23953963
TI  - A randomized trial comparing acetabular component fixation of two porous ingrowth
      surfaces using RSA.
AB  - Several new porous ingrowth surfaces for acetabular component fixation have
      recently been developed. The purpose of this study was to compare the in vivo
      fixation achieved by two different porosity ingrowth surfaces using
      radiostereometric analysis (RSA). Sixty-two patients undergoing primary total hip
      arthroplasty (THA) were randomized to receive a cementless acetabular component
      with either a 61% high porosity asymmetric titanium porous surface (StikTite,
      Smith and Nephew, TN, USA) or a 45% low porosity sintered bead porous surface
      (Roughcoat, Smith and Nephew, TN, USA). RSA and clinical follow-up examinations
      were done post-operatively, 6-weeks, 3-months, 6-months, 1-year and 2-years. Both
      the high porosity StikTite and lower porosity Roughcoat surfaces provided
      excellent biologic fixation. 

PMID- 23953962
TI  - One dose of tranexamic acid is safe and effective in revision knee arthroplasty.
AB  - Revision total knee arthroplasty (TKA) has been associated with an increased risk
      of perioperative blood loss. Tranexamic acid (TXA) has been proven to be safe and
      effective in preventing blood loss in primary TKA. The purpose of this study was
      to evaluate the effect of TXA on blood loss and transfusion rates in revision
      TKA. We performed a retrospective comparative study on 424 patients who had
      undergone revision TKA between January 2006 and March 2010. A total of 178
      patients did not receive TXA while 246 patients received one intraoperative dose
      of 20mg/kg of TXA given prior to tourniquet release. There was a significant
      reduction in hemoglobin loss (42+/-16g/L vs 38+/-15g/L, P=0.005), transfusion
      rates (30.3% vs 16.7%, P=0.001) and average amount transfused (1.1+/-1.9units vs
      0.5+/-1.1units, P=0.001) in the TXA group. There was no significant difference in
      recorded major adverse events with the administration of TXA. 

PMID- 23953964
TI  - Risk factors, causes, and the economic implications of unplanned readmissions
      following total hip arthroplasty.
AB  - In order to identify risk factors for readmissions following total hip
      arthroplasty (THA) and the causes and financial implications of such
      readmissions, we analyzed clinical and administrative data on 1583 consecutive
      primary THAs performed at a single institution. The 30-day readmission rate was
      6.51%. Increased age, length of stay, and body mass index were associated with
      significantly higher readmission rates. The most common re-admitting diagnoses
      were deep infection, pain, and hematoma. Average profit was lower for episodes of
      care with readmissions ($1548 vs. $2872, P=0.028). If Medicare stops reimbursing
      for THA readmissions, the institution under review would sustain an average net
      loss of $11,494 for episodes of care with readmissions and would need to maintain
      readmission rates below 23.6% in order to remain profitable. 

PMID- 23953965
TI  - Answer to Ferriero et al about "Measurement of the knee flexion angle...".

PMID- 23953966
TI  - Impulses and pressure waves cause excitement and conduction in the nervous
      system.
AB  - It is general accepted, that nerval excitement and conduction is caused by
      voltage changes. However, the influx of fluid into an elastical tube releases
      impulses or pressure waves. Therefore an influx of ion currents, respectively
      fluid motions into the elastic neuronal cells and fibres also induce impulses.
      This motion of charge carriers are measured by voltage devices as oscillations or
      action potentials, but the voltage changes may be an epiphenomenon of the
      (mechanical) impulses. Impulse waves can have a high speed. As stiffer or
      inelastic a tube wall, the greater is the speed of the impulse. Myelin sheaths
      cause a significant stiffening of the nerve fibre wall and myelinated fibres have
      a conduction velocity up to 120 m/s. The influx of fluid at the nodes of Ranvier
      intensifies periodically the impulse wave in the nerve fibres. The authors
      suggest that also the muscle end-plate acts as a conductor of axonal impulses to
      the inner of the muscle fibres and that the exocytosis of acetylcholine into the
      synaptic cleft may be an amplifier of the axonal impulse. It is discussed that
      intracellular actin filaments may also influence motions at the neuronal
      membrane. Many sensory nerve cells are excited due to exogenous or endogenous
      mechanical impulses. It may plausible that such impulses are conducted directly
      to the sensory nerve cell bodies in the dorsal root ganglia without the
      transformation in electric energy. Excitation conduction happens without
      noteworthy energy consumption because the flow of ion currents through the
      membranes takes place equivalent to the concentration gradient. Impulse waves
      cause short extensions of the lipid membranes of the cell- and fibres walls and
      therefore they can induce opening and closing of the included ion channels. This
      mechanism acts to "voltage gated" and "ligand-gated" channels likewise. The
      concept of neuronal impulses can be helpful to the understanding of other points
      of neurophysiology or neuronal diseases. This includes e.g., the brain concussion
      and pathohistological findings in Alzheimer dementia. To verify the concept of
      (mechanical) impulses in the nervous system it is necessary to carry out
      biophysical or mechanical investigations in very small dimensions and the authors
      hope to give for this a sufficient stimulus.

PMID- 23953967
TI  - Does the epiphyseal cartilage of the long bones have one or two ossification
      fronts?
AB  - Epiphyseal cartilage is hyaline cartilage tissue with a gelatinous texture, and
      it is responsible for the longitudinal growth of the long bones in birds and
      mammals. It is located between the epiphysis and the diaphysis. Epiphyseal
      cartilage also is called a growth plate or physis. It is protected by three bone
      components: the epiphysis, the bone bar of the perichondrial ring and the
      metaphysis. The epiphysis, which lies over the epiphyseal cartilage in the form a
      cupola, contains a juxtaposed bone plate that is near the epiphyseal cartilage
      and is in direct contact with the epiphyseal side of the epiphyseal cartilage.
      The germinal zone corresponds to a group of cells called chondrocytes. These
      chondrocytes belong to a group of chondral cells, which are distributed in rows
      and columns; this architecture is commonly known as a growth plate. The growth
      plate is responsible for endochondral bone growth. The aim of this study was to
      elucidate the causal relationship between the juxtaposed bone plate and
      epiphyseal cartilage in mammals. Our hypothesis is that cells from the germinal
      zone of the epiphyseal side of the epiphyseal cartilage are involved in forming a
      second ossification front that is responsible for the origin of the juxtaposed
      bone plate. We report the following: (a) The juxtaposed bone plate has a
      morphology and function that differs from that of the epiphyseal trabeculae; (b)
      on the epiphyseal edge of the epiphyseal cartilage, a new ossification front
      starts on the chondrocytes of the germinal area, which forms the juxtaposed bone
      plate. This ossification front is formed by chondrocytes from the germinal zone
      through a process of mineralisation and ossification, and (c) the process of
      mineralisation and ossification has a certain morphological analogy to the
      process of ossification in the metaphyseal cartilage of amphibians and differs
      from the endochondral ossification process in the metaphyseal side of the growth
      plate. The close relationship between the juxtaposed bone plate and the
      epiphyseal cartilage, in which the chondrocytes that migrate from the germinal
      area play an important role in the mineralisation and ossification process of the
      juxtaposed bone plate, supports the hypothesis of a new ossification front in the
      epiphyseal layer of the epiphyseal plate. This hypothesis has several
      implications: (a) epiphyseal cartilage is a morphological entity with two
      different ossification fronts and two different functions, (b) epiphyseal
      cartilage may be a morphological structure with three parts: perichondrial ring,
      metaphyseal ossification front or growth plate, and epiphyseal ossification
      front, (c) all disease (traumatic or dysplastic) that affects some of these parts
      can have an impact on the morphology of the epiphyseal region of the bone, (d)
      there is a certain analogy between metaphyseal cartilage in amphibians and
      mammalian epiphyseal cartilage, although the former is not responsible for bone
      growth, (e) comparative histological and anatomy studies are also warranted, to
      shed light on the phylogenetic study of epiphyseal cartilage throughout the
      changes that occur in the animal species. 

PMID- 23953968
TI  - The association between neonatal ABO blood group and intraventricular hemorrhage
      in extremely low birth weight infants: a reply to a comment.

PMID- 23953969
TI  - Corneal topography for pancorneal toric edge rigid gas-permeable contact lens
      fitting in patients with keratoconus, and differences in age and gender.
AB  - PURPOSE: To determine whether pancorneal rigid gas-permeable toric edge contact
      lenses (pancorneal RGP-CL) fitting could be improved by using non-central corneal
      shape predictors, and to compare these parameters with respect to age and gender
      in patients with keratoconus. METHODS: The current study was a retrospective
      study including patients with clinically evident keratoconus (on
      videokeratography) from three medical centres located in the Netherlands. Medical
      history, visual acuity, refraction, and contact lens characteristics were
      documented. All participants underwent ophthalmic examination including
      measurement of K-values (steepest, flattest, mean, as a non-central parameter the
      minimum radius [K-minimum], and all combined) using corneal topography. Fitting
      of contact lenses was based on the fluorescence pattern as seen during slitlamp
      examination. RESULTS: A total of 378 eyes of 218 patients with keratoconus were
      included. Of these, 257 (68%) were fitted with a pancorneal RGP-CL. The central K
      values, K-steep and K-flat, performed well in predicting the base curve radius,
      though, for pancorneal RGP-CL the non-central K-minimum added most (35.5%) to the
      total explained variance in base curve radius. Regarding age and gender, women
      tended to have larger K-values than men. No differences in K-values were found
      with respect to age. DISCUSSION: We found that including the K-minimum as a non
      central parameter may improve prediction of the best base curve radius for
      pancorneal RGP-CL and may reduce the number of trial contact lenses. In line with
      other studies, suggestive evidence was found for a difference in pattern of
      progression of keratoconus with gender, but not with age.

PMID- 23953970
TI  - Moyamoya syndrome associated with sickle cell trait in a child.
AB  - Moyamoya syndrome is a chronic, progressive occlusion of cerebrovascular arteries
      that leads to the development of characteristic collateral vessels. It is usually
      accompanied with sickle cell disease and other hemoglobinopathies. We report a 7
      year-old boy, who admitted to our clinic with headache, diagnosed as moyamoya
      syndrome associated with sickle cell trait. To date, two such cases have been
      reported in the literature. As far as we know, this patient is the first child
      reported.

PMID- 23953971
TI  - Immunological functioning in Alzheimer's disease: differential effects of
      relative left versus right temporoparietal dysfunction.
AB  - The cerebral hemispheres are differentially involved in regulating immunological
      functioning and the neuropathology associated with Alzheimer's disease (AD) is
      asymmetrical. Thus, subgroups of AD patients may exhibit different patterns of
      immunological dysfunction. We explored this possibility in a group of AD patients
      and found that patients with low white blood cell counts and low lymphocyte
      numbers exhibited better performance on tests of right temporoparietal
      functioning. Also, a significant positive relationship exists between lymph
      numbers and performance on a test of left temporoparietal functioning. Thus, some
      AD patients have greater immunological dysfunction based on relative left versus
      right temporoparietal functioning. 

PMID- 23953972
TI  - Suppression mechanism of the calcium sensitivity in Saccharomyces cerevisiae
      ptp2Deltamsg5Delta double disruptant involves a novel HOG-independent function of
      Ssk2, transcription factor Msn2 and the protein kinase A component Bcy1.
AB  - In Saccharomyces cerevisiae, disruption of both protein phosphatase genes, PTP2
      and MSG5, causes calcium sensitivity while additional disruption of protein
      kinase genes BCK1, MKK1, SLT2, MCK1, YAK1 and SSK2 confers calcium tolerance.
      Although the roles of BCK1, MKK1 and SLT2 have been characterized recently, the
      mechanism of suppression of the calcium sensitivity by SSK2 disruption is poorly
      understood. In this study, genetic analysis revealed a novel, high osmolarity
      glycerol (HOG)-independent suppressor function of Ssk2 in relation to the Ptp2
      and Msg5-mediated calcium signaling. Through microarray analysis, we identified
      19 genes with distinct pattern of expression that is likely involved in the
      calcium sensitive phenotype of the ptp2Deltamsg5Delta double disruptant.
      Furthermore, we found msn2Delta and bcy1Delta as suppressors of the calcium
      sensitive phenotype. Our results suggest the interrelationship of a HOG
      independent function of Ssk2, transcription factor Msn2, protein kinase A-related
      protein Bcy1 and 19 rise and fall genes as responsible for the suppression
      mechanism of the ptp2Deltamsg5Delta double disruptant by ssk2Delta disruption. 

PMID- 23953974
TI  - Associated lateral process and posteromedial tubercle talus fractures with
      entrapment of the medial neurovascular bundle: a case report.
AB  - This paper describes a case of an isolated fracture of the lateral process of the
      talus associated with a fracture in the posteromedial tubercle of the talus with
      entrapment of the medial neurovascular bundle. Currently no similar cases have
      been published describing this type of neurovascular bundle injury. Furthermore,
      in contrast to previously published cases, both fractures were treated surgically
      despite the absence of posteromedial tubercle fracture displacement. This article
      reviews the literature and provides useful recommendations for the clinical
      management of similar cases in the future. 

PMID- 23953973
TI  - Molecular genetics of alkaloid biosynthesis in Nicotiana tabacum.
AB  - Alkaloids represent an extensive group of nitrogen-containing secondary
      metabolites that are widely distributed throughout the plant kingdom. The
      pyridine alkaloids of tobacco (Nicotiana tabacum L.) have been the subject of
      particularly intensive investigation, driven largely due to the widespread use of
      tobacco products by society and the role that nicotine (16) (see Fig. 1) plays as
      the primary compound responsible for making the consumption of these products
      both pleasurable and addictive. In a typical commercial tobacco plant, nicotine
      (16) comprises about 90% of the total alkaloid pool, with the alkaloids
      nornicotine (17) (a demethylated derivative of nicotine), anatabine (15) and
      anabasine (5) making up most of the remainder. Advances in molecular biology have
      led to the characterization of the majority of the genes encoding the enzymes
      directly responsible the biosynthesis of nicotine (16) and nornicotine (17),
      while notable gaps remain within the anatabine (15) and anabasine (5)
      biosynthetic pathways. Several of the genes involved in the transcriptional
      regulation and transport of nicotine (16) have also been elucidated.
      Investigations of the molecular genetics of tobacco alkaloids have not only
      provided plant biologists with insights into the mechanisms underlying the
      synthesis and accumulation of this important class of plant alkaloids, they have
      also yielded tools and strategies for modifying the tobacco alkaloid composition
      in a manner that can result in changing the levels of nicotine (16) within the
      leaf, or reducing the levels of a potent carcinogenic tobacco-specific
      nitrosamine (TSNA). This review summarizes recent advances in our understanding
      of the molecular genetics of alkaloid biosynthesis in tobacco, and discusses the
      potential for applying information accrued from these studies toward efforts
      designed to help mitigate some of the negative health consequences associated
      with the use of tobacco products. 

PMID- 23953975
TI  - Evaluating a community-based early childhood education and development program in
      Indonesia: study protocol for a pragmatic cluster randomized controlled trial
      with supplementary matched control group.
AB  - BACKGROUND: This paper presents the study protocol for a pragmatic cluster
      randomized controlled trial (RCT) with a supplementary matched control group. The
      aim of the trial is to evaluate a community-based early education and development
      program launched by the Government of Indonesia. The program was developed in
      collaboration with the World Bank with a total budget of US$127.7 million, and
      targets an estimated 738,000 children aged 0 to 6 years living in approximately
      6,000 poor communities. The aim of the program is to increase access to early
      childhood services with the secondary aim of improving school readiness.
      METHODS/DESIGN: The study is being conducted across nine districts. The baseline
      survey contained 310 villages, of which 100 were originally allocated to the
      intervention arm, 20 originally allocated to a 9-month delay staggered start, 100
      originally allocated to an 18-month delay staggered start and 90 allocated to a
      matched control group (no intervention). The study consists of two cohorts, one
      comprising children aged 12 to 23 months and the other comprising children aged
      48 to 59 months at baseline. The data collection instruments include child
      observations and task/game-based assessments as well as a questionnaire suite,
      village head questionnaire, service level questionnaires, household
      questionnaire, and child caretaker questionnaire. The baseline survey was
      conducted from March to April 2009, midline was conducted from April to August
      2010 and endline conducted early 2013. The resultant participation rates at both
      the district and village levels were 90%. At the child level, the participation
      rate was 99.92%. The retention rate at the child level at midline was 99.67%.
      DISCUSSION: This protocol paper provides a detailed record of the trial design
      including a discussion regarding difficulties faced with compliance to the
      randomization, compliance to the dispersion schedule of community block grants,
      and procurement delays for baseline and midline data collections. Considering the
      execution of the program and the resultant threats to the study, we discuss our
      analytical plan and intentions for endline data collection. TRIALS REGISTRATION:
      Current Controlled Trials ISRCTN76061874.

PMID- 23953977
TI  - Modeling myocardial growth and hypertrophy in engineered heart muscle.
AB  - The introduction of biomimetic culture paradigms has advanced myocardial tissue
      engineering fundamentally, enabling today the provision of engineered rodent and
      human heart muscle with features characteristically found in postnatal
      myocardium. This is in marked contrasts to "flat" cardiomyocyte cultures with
      their typically low degree of organotypic maturation. Here, we discuss the
      collagen hydrogel-based engineered heart muscle (EHM) technology and provide
      background information on its use in simulations of myocardial growth and
      disease. 

PMID- 23953976
TI  - Successes and challenges of using whole exome sequencing to identify novel genes
      underlying an inherited predisposition for thoracic aortic aneurysms and acute
      aortic dissections.
AB  - Thoracic aortic aneurysms involving the aortic root and/or ascending aorta can
      lead to acute aortic dissections. Approximately 20% of patients with thoracic
      aortic aneurysms and dissections (TAAD) have a family history of the disease,
      referred to as familial TAAD (FTAAD) that can be inherited in an autosomal
      dominant manner with variable expression with respect to disease presentation,
      age of onset and associated features. Whole exome sequencing (WES) has been used
      to identify causative mutations in novel genes for TAAD. The strategy used to
      reduce the large number of rare variants identified using WES is to sequence
      distant relatives with TAAD and filter for heterozygous rare variants that are
      shared between the relatives, predicted to disrupt protein function and segregate
      with the TAAD phenotype in other family members. Putative genes are validated by
      identifying additional families with a causative mutation in the genes. This
      approach has successfully identified novel genes for FTAAD. 

PMID- 23953978
TI  - Homeobox transcription factor Pitx2: The rise of an asymmetry gene in
      cardiogenesis and arrhythmogenesis.
AB  - The homeobox transcription factor Pitx2 displays a highly specific expression
      pattern during embryogenesis. Gain and loss of function experiments have
      unraveled its pivotal role in left-right signaling. Conditional deletion in mice
      has demonstrated a complex and intricate role for Pitx2 in distinct aspects of
      cardiac development and more recently a link to atrial fibrillation has been
      proposed based on genome-wide association studies. In this review we will revise
      the role of Pitx2 in the developing heart, starting from the early events of left
      right determination followed by its role in cardiac morphogenesis and ending with
      its role in cardiac arrhythmogenesis. 

PMID- 23953979
TI  - Genomic instability and vascular aging: a focus on nucleotide excision repair.
AB  - Genomic instability is recognized as one of the primary mechanisms that lead to
      organismal aging. When genomic maintenance systems, such as nucleotide excision
      repair, are defective, genomic instability is promoted, which causes accelerated
      aging (progeria). This can be observed in humans as well as in mouse models of
      progeroid syndromes. The role of genomic instability related to nuclear DNA is
      currently under investigation with respect to its role in cardiovascular disease,
      and in particular those cardiovascular diseases that are associated with vascular
      aging. In this review, we highlight the first findings in this field of research
      that come from experiments in nucleotide excision repair-defective mouse models
      and from genetic studies. Possible mechanisms that mediate the consequences of
      genomic instability at the local vascular and at the systemic level, such as cell
      senescence, mutations, mitochondrial damage, and sirtuin 1 and IGF-1 decrease,
      are discussed and important goals for future research are set. 

PMID- 23953980
TI  - Myoglobin's novel role in nitrite-induced hypoxic vasodilation.
AB  - Hypoxic vasodilation represents a key physiological response of the
      cardiovascular system to low tissue oxygen tension, adjusting local blood flow to
      meet the metabolic requirements in tissue. Vasodilation occurs by nitric oxide
      (NO) activation of the cyclic guanosine monophosphate (cGMP) signaling pathway in
      vascular smooth muscle cells. Under normoxia, NO is formed by the well-known
      endothelial NO synthase (eNOS) system while under hypoxia NO is generated from
      nitrite. We have unraveled the heme-protein myoglobin in vascular smooth muscle
      cells as a major source of NO generation by reduction of endogenous nitrite under
      hypoxia. This mediates hypoxic vasodilation under physiological conditions
      without direct involvement of eNOS and independently of effects on cardiac
      function. 

PMID- 23953981
TI  - Pharmacy research on health literacy can contribute to national goals and health
      care system improvements.

PMID- 23953982
TI  - Examination of psychosocial predictors of Virginia pharmacists' intention to
      utilize a prescription drug monitoring program using the theory of planned
      behavior.
AB  - BACKGROUND: Little is known about the main drivers of pharmacists' intention to
      utilize prescription drug monitoring programs (PDMPs) when making care decisions
      and the actual contribution of these factors in explaining intention and
      behavior. OBJECTIVES: This study examined what theory of planned behavior (TPB)
      model constructs (i.e., attitude, subjective norm [SN], perceived behavioral
      control [PBC]), past utilization behavior (PUB) and perceived moral obligation
      (PMO) were significant predictors of Virginia community pharmacists' intention to
      utilize a PDMP. METHODS: A cover letter with a link to a 28-item online survey
      was e-mailed to 600 members of the Virginia Pharmacists Association. Multiple
      regression analyses were used to determine the association between pharmacists'
      intention to utilize the PDMP database and attitude, SN, PBC, PUB and PMO.
      RESULTS: Ninety-seven usable responses were received, for a response rate of
      16.2%. A majority of the respondents were Caucasian (96.4%), female (50.5%),
      working in independent community pharmacies (60.4%) with an average age of 49.5
      +/- 13.4 years. Overall, pharmacists intended to utilize a PDMP (mean = 5.3 +/-
      4.6; possible range: -9 to 9), had a positive attitude toward utilizing PDMP
      (mean = 6.3 +/- 5.3; possible range: -12 to 12), perceived that others wanted
      them to utilize a PDMP (SN score = 3.7 +/- 2.4; range: -6 to 6), and believed
      that they had control over utilization behavior (PBC score = 4.5 +/- 4.0; range: 
      9 to 9). Attitude (beta = 0.723, P < 0.001), SN (beta = 0.230, P = 0.014) and PBC
      (beta = -0.215, P = 0.026) significantly predicted pharmacists' intent,
      accounting for 56.7% of the variance in intention to utilize the PDMP database (P
      < 0.001). The addition of PMO (P < 0.001) significantly contributed to explaining
      the variance in intention but PUB did not. CONCLUSIONS: Members of the Virginia
      Pharmacists Association who responded to the survey showed a strong positive
      intent to utilize PDMP database. Pharmacists' attitudes, subjective norm,
      perceived behavioral control and perceived moral obligation were significant
      predictors of intention but past utilization behavior was not. The TPB is a
      useful theoretical framework when predicting PDMP utilization behavior of
      community pharmacists, accounting for 56.7% of the variance in intention.

PMID- 23953984
TI  - Platelet activity measured by a rapid turnaround assay identifies coronary artery
      bypass grafting patients at increased risk for bleeding and transfusion
      complications after clopidogrel administration.
AB  - BACKGROUND: We sought to establish a metric for easily estimating bleeding and
      transfusion risks for cardiac surgery patients after antiplatelet agent use.
      METHODS: Deidentified records of patients who underwent coronary artery bypass
      grafting (CABG) at our institution (January 2010-June 2011) were searched for
      patients without identified risk factors for excessive bleeding who underwent
      documented P2Y12 testing after clopidogrel administration (n = 276). Clinical
      outcomes were analyzed according to whether preoperative platelet function was
      higher (platelet reactivity units [PRUs], >=237) or lower (PRU, <237) and
      according to preoperative PRU cutoffs: high (>290, or no clopidogrel),
      intermediate (200-290), or low (<200). RESULTS: Eighty-five patients (57%)
      received allogeneic blood products at 24 hours or less postoperatively: 33 (22%)
      received fresh frozen plasma, and 57 (38%) received platelets. The median 12-hour
      chest tube output (CTO) was 350 mL (interquartile range, 260-490 mL); CTO was
      "high" (>437 mL) in 62 (42%) of the clopidogrel-treated patients. Lower-PRU
      patients were more likely to receive coagulation factors (odds ratio [OR], 2.82;
      P = .0004) and to have high CTO or coagulation factor transfusion (OR, 2.35; P =
      .02) than higher-PRU patients. Likewise, intermediate- and low-PRU patients had
      incrementally greater incidences of high CTO (OR, 1.72; P = .002) and coagulation
      factor transfusion (OR, 2.08; P < .0001) than high-PRU/no clopidogrel patients.
      High CTO or coagulation factor transfusion was more frequent in intermediate-PRU
      (OR, 2.67; P = .02) and low-PRU (OR, 5.08; P = .0002) patients than in high
      PRU/no clopidogrel patients. CONCLUSIONS: Among clopidogrel-treated CABG
      patients, preoperative platelet function testing can identify those at increased
      risk for postoperative bleeding and transfusion.

PMID- 23953985
TI  - Continuous-flow left ventricular assist device implantation in the presence of a
      hostile ventricular apex.

PMID- 23953986
TI  - Housing and child health. Foreword.

PMID- 23953987
TI  - Housing and child health.
AB  - The connection between housing and health is well established. Physical,
      chemical, and biological aspects of the child's home, such as cleanliness,
      moisture, pests, noise, accessibility, injury risks, and other forms of housing
      environmental quality, all have the potential to influence multiple aspects of
      the health and development of children. Basic sanitation, reduced household
      crowding, other improvements in housing and expanded, and improved housing
      regulations have led to advances in children's health. For example, lead
      poisoning prevention policies have profoundly reduced childhood lead exposure in
      the United States. This and many other successes highlight the health benefits
      for families, particularly children, by targeting interventions that reduce or
      eliminate harmful exposures in the home. Additionally, parental mental health
      problems, food insecurity, domestic violence, and the presence of guns in
      children's homes all are largely experienced by children in their homes, which
      are not as yet considered part of the Healthy Homes agenda. There is a large
      movement and now a regulatory structure being put in place for healthy housing,
      which is becoming closely wedded with environmental health, public health, and
      the practice of pediatrics. The importance of homes in children's lives, history
      of healthy homes, asthma, and exposures to lead, carbon monoxide,
      secondhand/thirdhand smoke, radon, allergy triggers is discussed, as well as how
      changes in ambient temperature, increased humidity, poor ventilation, water
      quality, infectious diseases, housing structure, guns, electronic media, family
      structure, and domestic violence all affect children's health. 

PMID- 23953988
TI  - Intravenous lacosamide as treatment option in post-stroke non convulsive status
      epilepticus in the elderly: a proof-of-concept, observational study.
AB  - PURPOSE: To evaluate the efficacy and safety of intravenously administered
      lacosamide (iv LCM) in post-stroke non convulsive status epilepticus (NCSE) in
      elderly patients. METHODS: We enrolled 16 patients (7 M/9 F; 77 +/- 7 years of
      age) with NCSE. iv LCM was used in all the patients as initial treatment (i.e.
      patients were directly started on LCM) at a loading dose of 400 mg over 30 min,
      followed by a mean maintenance dose of 400 mg per day. iv LCM was considered as
      effective in patients who experience no NCSE for 24 h following treatment, as
      evaluated by EEG recording and clinical observation. RESULTS: LCM was effective
      in treating NCSE in eight of the sixteen patients in whom epileptic activity
      disappeared (7/8) or was significantly reduced (1/8) within 45-60 min after
      administration. None of these patients relapsed in the following 24 h. No adverse
      events were observed. A partial anterior circulation syndrome (PACS) was present
      in 10 patients while a total anterior circulation syndrome (TACS) in six.
      CONCLUSIONS: This pilot study suggests that LCM exhibits safety and efficacy
      profiles which make it an optimal candidate as a first-choice drug against post
      stroke NCSE in elderly patients. A prospective comparative trial is needed to
      confirm these preliminary data.

PMID- 23953989
TI  - Association of eating speed and energy intake of main meals with overweight in
      Chinese pre-school children.
AB  - OBJECTIVE: To investigate the association between eating behaviours (eating speed
      and energy intake of main meals) and overweight in pre-school children. DESIGN:
      Cross-sectional study. Data consisted of measurements (height and weight),
      questionnaire information (eating behaviours of eating speed and overeating) and
      on-site observation data (meal duration and energy intake of main meals).
      SETTING: Seven kindergartens in Beijing, China. SUBJECTS: Pre-school children (n
      1138; age range 3.1-6.7 years old) from seven kindergartens participated in the
      study. RESULTS: The multivariate-adjusted odds ratio of overweight in
      participants with parent-reported 'more than needed food intake' was 3.02 (95 %
      CI 2.06, 4.44) compared with the 'medium food intake' participants, and higher
      eating speed was associated with childhood overweight. For the two observed
      eating behaviours, each 418.7 kJ (100 kcal) increase of lunch energy intake
      significantly increased the likelihood for overweight by a factor of 1.445, and
      each 5-min increase in meal duration significantly decreased the likelihood for
      overweight by a factor of 0.861. Increased portions of rice and cooked dishes
      were significantly associated with overweight status (OR = 2.274; 95 % CI 1.360,
      3.804 and OR = 1.378; 95 % CI 1.010, 1.881, respectively). CONCLUSIONS: Eating
      speed and excess energy intake of main meals are associated with overweight in
      pre-school children.

PMID- 23953990
TI  - Pomegranate seed oil prevents bone loss in a mice model of osteoporosis, through
      osteoblastic stimulation, osteoclastic inhibition and decreased inflammatory
      status.
AB  - In the current context of longer life expectancy, the prevalence of osteoporosis
      is increasingly important. This is why development of new strategies of
      prevention is highly suitable. Pomegranate seed oil (PSO) and its major
      component, punicic acid (a conjugated linolenic acid), have potent anti
      inflammatory and anti-oxidative properties both in vitro and in vivo, two
      processes strongly involved in osteoporosis establishment. In this study, we
      demonstrated that PSO consumption (5% of the diet) improved significantly bone
      mineral density (240.24+/-11.85 vs. 203.04+/-34.19 mg/cm(3)) and prevented
      trabecular microarchitecture impairment in ovariectomized (OVX) mice C57BL/6J,
      compared to OVX control animals. Those findings are associated with
      transcriptional changes in bone tissue, suggesting involvement of both
      osteoclastogenesis inhibition and osteoblastogenesis improvement. In addition,
      thanks to an ex vivo experiment, we provided evidence that serum from mice fed
      PSO (5% by gavage) had the ability to significantly down-regulate the expression
      of specific osteoclast differentiation markers and RANK-RANKL downstream
      signaling targets in osteoclast-like cells (RAW264.7) (RANK: negative 0.49-fold
      vs. control conditions). Moreover, in osteoblast-like cells (MC3T3-E1), it
      elicited significant increase in alkaline phosphatase activity (+159% at day 7),
      matrix mineralization (+271% on day 21) and transcriptional levels of major
      osteoblast lineage markers involving the Wnt/beta-catenin signaling pathways. Our
      data also reveal that PSO inhibited pro-inflammatory factors expression while
      stimulating anti-inflammatory ones. These results demonstrate that PSO is highly
      relevant regarding osteoporosis. Indeed, it offers promising alternatives in the
      design of new strategies in nutritional management of age-related bone
      complications. 

PMID- 23953991
TI  - Effect of salicylic acid on the attenuation of aluminum toxicity in Coffea
      arabica L. suspension cells: A possible protein phosphorylation signaling
      pathway.
AB  - The protective effect of salicylic acid (SA) on aluminum (Al) toxicity was
      studied in suspension cells of Coffea arabica L. The results showed that SA does
      not produce any effect on cell growth and that the growth inhibition produced by
      aluminum is restored during simultaneous treatment of the cells with Al and SA.
      In addition, the cells exposed to both compounds, Al and SA, showed evident
      morphological signals of recovery from the toxic state produced in the presence
      of Al. The cells treated with SA showed a lower accumulation of Al, which was
      linked to restoration from Al toxicity because the concentration of Al(3+)
      outside the cells, measured as the Al(3+)-morin complex, was not modified by the
      presence of SA. Additionally, the inhibition of phospholipase C by Al treatment
      was restored during the exposure of the cells to SA and Al. The involvement of
      protein phosphorylation in the protective effect of SA on Al-toxicity was
      suggested because staurosporine, a protein kinase inhibitor, reverted the
      stimulatory effect of the combination of Al and SA on protein kinase activity.
      These results suggest that SA attenuates aluminum toxicity by affecting a
      signaling pathway linked to protein phosphorylation.

PMID- 23953992
TI  - Excess Ca(2+) does not alleviate but increases the toxicity of Hg(2+) to
      photosystem II in Synechocystis sp. (Cyanophyta).
AB  - This study demonstrated that excess Ca(2+) increased the toxicity of Hg(2+) to
      PSII of cyanobacterium Synechocystis sp. using fast rise chlorophyll fluorescence
      test. Excess Ca(2+) increased the inhibitory effect of Hg(2+) on O2 evolution.
      Exposure to Hg(2+) caused increase in functional antenna size (ABS/RC), trapping
      rate of reaction center (TR0/RC), dissipated energy flux per reaction center
      (DI0/RC) and maximum quantum yield of non-photochemical deexcitation ( [Formula:
      see text] ), indicating that some reaction centers were transformed to
      dissipation sinks under Hg(2+) stress. Hg(2+) stress slowed down electron
      transport on both donor side and acceptor side and caused accumulation of
      P680(+). Excess Ca(2+) intensified all the Hg(2+) toxic effects on PSII function
      and led to dysfunction of PSII. The number of reaction centers that were
      transformed into dissipation sinks increased with increasing Ca(2+)
      concentration. 

PMID- 23953993
TI  - Effect of metal stress on photosynthetic pigments in the Cu-hyperaccumulating
      lichens Cladonia humilis and Stereocaulon japonicum growing in Cu-polluted sites
      in Japan.
AB  - To understand the ecology and physiology of metal-accumulating lichens growing in
      Cu-polluted sites, we investigated lichens near temple and shrine buildings with
      Cu roofs in Japan and found that Stereocaulon japonicum Th. Fr. and Cladonia
      humilis (With.) J. R. Laundon grow in Cu-polluted sites. Metal concentrations in
      the lichen samples collected at some of these sites were determined by
      inductively coupled plasma mass spectroscopy (ICP-MS). UV-vis absorption spectra
      of pigments extracted from the lichen samples were measured, and the pigment
      concentrations were estimated from the spectral data using equations from the
      literature. Secondary metabolites extracted from the lichen samples were analyzed
      by high-performance liquid chromatography (HPLC) with a photodiode array
      detector. We found that S. japonicum and C. humilis are Cu-hyperaccumulating
      lichens. Differences in pigment concentrations and their absorption spectra were
      observed between the Cu-polluted and control samples of the 2 lichens. However,
      no correlation was found between Cu and pigment concentrations. We observed a
      positive correlation between Al and Fe concentrations and unexpectedly found high
      negative correlations between Al and pigment concentrations. This suggests that
      Al stress reduces pigment concentrations. The concentrations of secondary
      metabolites in C. humilis growing in the Cu-polluted sites agreed with those in
      C. humilis growing in the control sites. This indicates that the metabolite
      concentrations are independent of Cu stress. 

PMID- 23953994
TI  - Duddingtonia flagrans chlamydospores in nutritional pellets: effect of storage
      time and conditions on the trapping ability against Haemonchus contortus larvae.
AB  - The study evaluated the effect of storage time and conditions of nutritional
      pellets (NP) containing Duddingtonia flagrans chlamydospores on its in vitro
      trapping ability against Haemonchus contortus L3 larvae. The treated batch (200
      NP) contained 4 * 106 chlamydospores of the FTH0-8 strain, whereas the control
      batch (200 NP) was produced without spores. Both NP batches were exposed to four
      experimental storage conditions: (T1) shelves (indoors); (T2) refrigeration (4
      degrees C); (T3) outdoors under a roof; and (T4) 100% outdoors. Each group
      comprised 48 NP with spores and 48 NP without spores (control). The ability of D.
      flagrans spores to trap H. contortus L3 larvae was evaluated for 8 weeks for each
      storage condition. For that purpose, six randomly selected NP with spores were
      compared to their respective control NP. Each NP was individually crushed. The
      crushed material (1 g) was placed on the surface of a 2% water agar plate with
      200 H. contortus L3 larvae. Plates were sealed and were incubated at room
      temperature for 8 days. The whole content of every plate was transferred to a
      Baermann apparatus to recover the remaining larvae. There was a clear larval
      reduction in the NP with spores, compared to the respective control NP in the
      four storage conditions (P< 0.05). The mean reductions ( +/- SEM) of the storage
      conditions were 67 +/- 4.9 (T2), 77 +/- 6.1 (T1), 81.5 +/- 3.8 (T4) and 82.1 +/-
      2.5 (T3). Larval reductions were similar at all times and were not affected by
      storage conditions or storage time (R 20.05). The long-term shelf-life of the
      chlamydospores in the NP suggests that this spore dosage technology is a viable
      option.

PMID- 23953995
TI  - Accommodating the human response for realistic adaptation planning: response to
      Watson and Segan.

PMID- 23953996
TI  - Defining and defending Connell's intermediate disturbance hypothesis: a response
      to Fox.

PMID- 23953997
TI  - Atypical Bickerstaff brainstem encephalitis: pitfalls of diagnosis.

PMID- 23953999
TI  - Cell polarity and development.

PMID- 23953998
TI  - Review of the state of renal nerve ablation for patients with severe and
      resistant hypertension.
AB  - Through modulation of renin secretion, glomerular filtration rate, and renal
      absorption of sodium, the sympathetic innervation of the kidneys plays an
      important role in the pathogenesis of hypertension. Renal nerve ablation
      technology is being developed for treatment of drug-treatment-resistant
      hypertension worldwide. Preliminary research with the use of radiofrequency-based
      renal denervation systems have demonstrated encouraging results with significant
      reduction of blood pressure in patients inadequately controlled despite nearly
      maximal drug therapy regimens. From work done thus far, the renal denervation
      procedure has not been associated with serious adverse effects. Long-term
      efficacy and safety still needs to be established for renal nerve ablation. This
      review focuses on the impact of the renal sympathetic system on blood pressure
      regulation, the clinical rationale for renal nerve ablation in severe and drug
      treatment-resistant hypertension, and current evidence from the more advanced
      renal denervation devices. 

PMID- 23954000
TI  - The origins and mechanisms of karrikin signalling.
AB  - Karrikins are butenolides in smoke and char that stimulate seed germination.
      Karrikin action in Arabidopsis requires the F-box protein MAX2 and the alpha/beta
      hydrolase KAI2, a paralogue of D14 that is required for perception of
      strigolactones (SL). SL response involves hydrolysis by D14, whereas karrikins
      bind to KAI2 without apparent hydrolysis. We discuss the current understanding of
      the mechanisms of karrikin perception and response. The usual function of KAI2 is
      unclear, but we hypothesise that the similarity between karrikins and the
      endogenous ligand for KAI2 made adaptation of some plants to karrikins possible. 

PMID- 23954003
TI  - The uniqueness of elderly care: registered nurses' experience as preceptors
      during clinical practice in nursing homes and home-based care.
AB  - The expected shortage of registered nurses with an advanced degree as specialists
      in geriatric care or gerontology is imminent. Previous studies report that
      clinical practice where student nurses are supervised by registered nurses has a
      direct impact on how students perceive nursing as a profession and future career
      choice. Considering the anticipated need for well-educated and specialised nurses
      it is therefore, relevant as well as necessary to describe clinical learning with
      a focus on preceptorship in geriatric nursing care. This paper is a report of a
      study describing registered nurses' experience of precepting undergraduate
      student nurses during clinical practice in nursing homes and home-based care. A
      qualitative design, based on seven focus group interviews, was employed with 30
      registered nurses with preceptor experience from nursing homes and home-based
      care for the elderly. Our findings present three precepting strategies that are
      unique to elderly care: preparing students for end of life care, facilitating a
      respectful approach to the older person and promoting creativity and independent
      work. The findings are discussed using a socio-cultural perspective and
      illustrate how communities of elderly practice can be valuable learning
      environments. 

PMID- 23954004
TI  - Cardiac transplantation after bridged therapy with continuous flow left
      ventricular assist devices.
AB  - INTRODUCTION: Cardiac transplantation is an effective surgical therapy for end
      stage heart failure. Patients (pts) may need to be bridged with a continuous flow
      left ventricular assist device (CF-LVAD) while on the transplant list as logistic
      factors like organ availability are unknown. Cardiac transplantation post-LVAD
      can be a surgically challenging procedure and outcome in these pts is perceived
      to be poorer based on experience with earlier generation pulsatile flow pumps.
      Data from a single institution comparing these pts with those undergoing direct
      transplantation in the present era of continuous flow device therapy are limited.
      AIM: Evaluate results of cardiac transplantation in pts bridged with a CF-LVAD
      (BTx) and compare outcomes with pts undergoing direct transplantation (Tx) in a
      single institution. RESULTS: From June 2007 till January 2012, 106 pts underwent
      cardiac transplantation. Among these, 37 (35%) pts (51+/-11 years; 85% male) were
      bridged with a CF-LVAD (BTx), while 70 (65%) comprised the Tx group (53+/-12
      years; 72% males). The median duration of LVAD support was 227 (153,327) days.
      During the period of LVAD support, 10/37 (27%) pts were upgraded to status 1A and
      all were successfully transplanted. Median hospital stay in the BTx (14 days) was
      slightly longer than the Tx group (12 days) but not statistically significant
      (p=0.21). In-hospital mortality in the BTx (5%) and Tx (1%) were comparable
      (p=0.25). Estimated late survival in the BTx cohort was 94+/-7, 90+/-10 and 83+/
      16% at the end of one, two and three years, respectively which was comparable to
      97+/-4%, 93+/-6% and 89+/-9% for the Tx group (p=0.50). CONCLUSION: Cardiac
      transplantation after LVAD implant can be performed with excellent results.
      Patients can be supported on the left ventricular assist device even for periods
      close to a year with good outcome after cardiac transplantation.

PMID- 23954005
TI  - Efficacy and safety of bepridil for prevention of ICD shocks in patients with
      Brugada syndrome and idiopathic ventricular fibrillation.

PMID- 23954006
TI  - Tako-Tsubo cardiomyopathy recurrence in an elderly woman firstly diagnosed with
      acute myocardial infarction: how many cold cases to be reclassified?

PMID- 23954007
TI  - Atrial fibrillation in patients with acute coronary syndromes.

PMID- 23954008
TI  - Cytokine removal on extracorporeal life support for treatment of acute
      endotoxemia: a randomized controlled animal study.
AB  - BACKGROUND: We prospectively evaluated the effectiveness of resin adsorption
      incorporated in an extracorporeal life support (ELS) circuit in an animal model
      of sepsis for removal of cytokines and prevention of hemodynamic deterioration
      during the treatment of septic shock. METHODS: Twelve female landrace pigs were
      randomly assigned to two groups, a study group(n=6), treated with high-flow resin
      adsorption (300 mL/min) and ELS, and a control group (n=6), treated only with
      ELS. Septic shock was induced by intravenous 0.02 MUg/kg/min infusion was of
      Escherichia coli lipopolysaccharide (LPS). Measurements were carried out in the
      study group at baseline, at the end of LPS injection(t0) at 30(t1), 60(t2),
      90(t3) and 120 min (t4) and 60 min after stopping resin-adsorption (t5). In the
      control group measurements were performed at baseline (t0), t1 and only t2, as no
      control animal survived beyond this latter experimental timepoint. RESULTS: The
      final population consisted of 9 animals, five in the study group and 4 in the
      control group. Plasma values of both tumor necrosis factor alpha (TNF-alpha) and
      interleukin-6 (IL-6) were reduced during resin-adsorption (t1-t4) while these
      mediators increased in controls undergoing ELS only. With a clearance of TNF
      alpha of 15,233 pg/min and IL-6 of 10,233 pg/min, 79.2% of TNF-alpha and 95.3% of
      IL-6 produced were adsorbed. Systemic vascular resistance decreased significantly
      in both groups at t0. While it further was reduced during the control experiments
      at t1 and t2, it returned to normal in the study animals. Cardiac output
      increased at t0, t1 and t2 in the control experiments. In contrast, in study
      animals after a peak at t0, it returned to the baseline value and did not vary
      thereafter. CONCLUSIONS: Combined resin-adsorption and ELS improved hemodynamics
      resulting from effective removal of inflammatory mediators in a pig model of
      septic shock.

PMID- 23954009
TI  - Meta-analysis of the outcome of patients with low gradient severe aortic stenosis
      and preserved left ventricular ejection fraction.

PMID- 23954010
TI  - Angiopoietin-1 gene plasmid and bone marrow mononuclear cell transfer accelerates
      reendothelialization in rat carotid arteries after balloon injury.

PMID- 23954011
TI  - Underdiagnosis and pharmacovigilance. The case of allergic acute coronary
      syndrome (Kounis syndrome).

PMID- 23954012
TI  - Relationship between CHA(65)DS(2) score and obstructive sleep apnea (CHA(65)DS(2)
      and OSA).

PMID- 23954013
TI  - Influence of MRE11, RAD50 and NIBRIN protein expression on survival in pancreatic
      carcinoma after curative resection.
AB  - The MRE11/RAD50/NIBRIN complex, a protein complex that repairs DNA double-strand
      breaks, could serve as an early marker for new lesions in pancreatic cancer. We
      determined the expression of MRE11, RAD50 and NIBRIN, and their possible
      prognostic value regarding survival. Forty-one patients with ductal
      adenocarcinoma of the pancreas were included. All underwent curative surgery.
      Immunohistochemistry was performed for MRE11, RAD50 and NIBRIN. Subsequent
      analyses were based on a modified immunoreactive score. Statistical analysis was
      conducted using the statistics program "R". The mean follow-up period was 509
      days. The mean age of the patients was 67+/-8 years, male=56%, female=44%. Eighty
      seven percent underwent a Kausch-Whipple procedure, whereas a left side resection
      was performed in 22% of patients. Positive lymph nodes were found in 80% of
      cases, and patients were staged UICC IIa (12%), IIb (56%) and IV (29%). Overall
      significant results were found for MRE11 (p=0.02) and NIBRIN (p=0.01) expression
      and postoperative survival. We found a significant relation between the
      expression of MRE11, NIBRIN and the postoperative survival of patients with
      ductal adenocarcinoma. The link between the expression of the MRN complex, ATM
      and pancreatic cancer can be used to develop new treatment options for pancreatic
      carcinoma. 

PMID- 23954014
TI  - Pulmonary cryptococcosis in rheumatoid arthritis (RA) patients: comparison of
      imaging characteristics among RA, acquired immunodeficiency syndrome, and
      immunocompetent patients.
AB  - PURPOSE: The imaging characteristics of cryptococcosis in rheumatoid arthritis
      (RA) patients were analyzed by comparing them with those of acquired
      immunodeficiency syndrome (AIDS) and immunocompetent patients, and the imaging
      findings were correlated with pathological findings. METHODS: Two radiologists
      retrospectively compared the computed tomographic (CT) findings of 35 episodes of
      pulmonary cryptococcosis in 31 patients with 3 kinds of underlying states (10 RA,
      12 AIDS, 13 immunocompetent), focusing on the nature, number, and distribution of
      lesions. The pathological findings of 18 patients (8 RA, 2 AIDS, 8
      immunocompetent) were analyzed by two pathologists, and then correlated with
      imaging findings. RESULTS: The frequencies of consolidation and ground glass
      attenuation (GGA) were significantly higher, and the frequency of peripheral
      distribution was significantly lower in the RA group than in the immunocompetent
      group. Peripheral distribution was less common and generalized distribution was
      more frequent in the RA group than in the AIDS group. The pathological findings
      of the AIDS and immunocompetent groups reflected their immune status: There was
      lack of a granuloma reaction in the AIDS group, and a complete granuloma reaction
      in the immunocompetent group, while the findings of the RA group varied,
      including a complete granuloma reaction, a loose granuloma reaction and a hyper
      immune reaction. Cases with the last two pathologic findings were symptomatic and
      showed generalized or central distribution on CT. CONCLUSION: Cryptococcosis in
      the RA group showed characteristic radiological and pathological findings
      compared with the other 2 groups.

PMID- 23954015
TI  - In vivo DTI longitudinal measurements of acute sciatic nerve traction injury and
      the association with pathological and functional changes.
AB  - OBJECTIVE: To explore the feasibility of longitudinally measuring acute traction
      injury to the sciatic nerve using 1.5 T clinical MRI scanner of diffusion tensor
      imaging (DTI) and to analyze the associations of the measurements [regarding
      fractional anisotropy (FA), apparent diffusion coefficient (ADC), eigenvalue
      (lambda|| and lambda?)] with limb function and pathology. MATERIALS AND METHODS:
      Acute traction injuries to the sciatic nerve were created in the right hind limbs
      of 32 New Zealand white rabbits, the left hind limbs were chosen as sham
      operation nerves. MRI scans were performed at intervals from pre-operation
      through 8 weeks post-operation follow up. Scanning sequences included T2WI, STIR,
      and single shot spin echo DTI with single shot EPI acquisition (SE-DTI-SSEPI).
      Parameters of FA, ADC, axial diffusivity (lambda||) and radial diffusivity
      (lambda?) were then calculated from the DTI. The limb functions and pathologic
      changes were evaluated and compared. RESULTS: Diffusion Tensor Tractography (DTT)
      only revealed the proximal portion of the injured nerves 1-3 days after traction
      injury but did not reveal the nerve of the distal and traction portions at all.
      Nerve fibers of the distal and traction portions were not revealed by DTT until
      after the 1st week. They were elongated gradually and recovered almost to the
      normal at 8th week. The value of FA and lambda?of the injured nerves, which
      varied in different portions, were significantly different between the traction
      injury nerves and the sham operation nerves, whereas the value of ADC and
      lambda|| were not significantly different. The curve lines of FA value-time for
      the proximal, traction and distal portions of the injured nerve correlated well
      to the functional and pathological changes of the limb affected, while the DTI
      parameters did not change that much in the sham-operated nerves. CONCLUSIONS: DTI
      obtained on a 1.5 T clinical MRI scanner can demonstrate early abnormal changes
      following traction injury to the sciatic nerve in rabbits. The curve lines of FA
      time and lambda?-time for nerve traction injury are consistent with the
      pathological and functional changes of the limb affected. DTI may thus be a
      sensitive and reliable method to evaluate degeneration and regeneration of the
      nerve after traction injury.

PMID- 23954016
TI  - Cumulative radiation exposure and cancer risk of patients with ischemic heart
      diseases from diagnostic and therapeutic imaging procedures.
AB  - OBJECTIVES: To present a detailed analysis of the cumulative radiation exposure
      and cancer risk of patients with ischemic heart diseases (IHD) from diagnostic
      and therapeutic imaging. METHODS: For 1219 IHD patients, personal and examination
      data were retrieved from the information systems of a university hospital. For
      each patient, cumulative organ doses and the corresponding effective dose (E)
      resulting from all imaging procedures performed within 3 months before and 12
      months after the date of the diagnosis were calculated. The cumulative lifetime
      attributable risk (LAR) of the patients to be diseased by radiation-related
      cancer was estimated using sex-, age-, and organ-specific risk models. RESULTS:
      Among the 3870 procedures performed in the IHD patients, the most frequent were
      radiographic examinations (52.4%) followed by coronary catheter angiographies and
      percutaneous cardiac interventions (41.3%), CT scans (3.9%), and perfusion SPECT
      (2.3%). 87% of patient exposure resulted from heart catheter procedures. E and
      LAR were significantly higher in males than females (average, 13.3 vs. 10.3 mSv
      and 0.09 vs. 0.07%, respectively). Contrary to the effective dose, the cancer
      risk decreased markedly for both sexes with increasing age. CONCLUSIONS: Although
      IHD patients were partially exposed to considerable amounts of radiation,
      estimated LARs were small as compared to their baseline risk to develop cancer in
      the remaining life.

PMID- 23954017
TI  - Intraoperative hyperthermia during cesarean section: a pertinent lesson.

PMID- 23954018
TI  - Considerations in the management of massive pulmonary embolism in pregnancy.

PMID- 23954019
TI  - In reply.

PMID- 23954020
TI  - QT interval prolongation following carbetocin in prevention of post-cesarean
      delivery hemorrhage.

PMID- 23954021
TI  - TBX6, LHX1 and copy number variations in the complex genetics of Mullerian
      aplasia.
AB  - BACKGROUND: Mullerian aplasia (MA) is a congenital disorder of the female
      reproductive tract with absence of uterus and vagina with paramount impact on a
      woman's life. Despite intense research, no major genes have been found to explain
      the complex genetic etiology. METHODS AND RESULTS: We have used several genetic
      methods to study 112 patients with MA. aCGH identified CNVs in 8/50 patients
      (16%), including 16p11.2 and 17q12 deletions previously associated with MA.
      Subsequently, another four patients were shown to carry the ~0.53 Mb deletion in
      16p11.2. More importantly, sequencing of TBX6, residing within 16p11.2, revealed
      two patients carrying a splice site mutation. Two previously reported TBX6
      variants in exon 4 and 6 were shown to have a significantly higher frequency in
      patients (8% and 5%, respectively) than in controls (2% each). We also sequenced
      LHX1 and found three apparently pathogenic missense variants in 5/112 patients.
      Altogether, we identified either CNVs or variations in TBX6 or LHX1 in 30/112
      (26.8%) MA patients. CNVs were found in 12/112 (10.7%), patients, novel variants
      in TBX6 or LHX1 in 7/112 (6.3%), and rare variants in TBX6 in 15/112 (13.4%)
      patients. Furthermore, four of our patients (4/112, 3.6%) were shown to carry
      variants in both TBX6 and LHX1 or a CNV in combination with TBX6 variants lending
      support to the complex genetic etiology of MA. CONCLUSIONS: We have identified
      TBX6 as a new gene associated with MA. Our results also support the relevance of
      LHX1 and CNVs in the development of this congenital malformation.

PMID- 23954022
TI  - Does interhemispheric communication relate to the bilateral function of muscles?
      A study of scapulothoracic muscles using transcranial magnetic stimulation.
AB  - Interhemispheric connections have been demonstrated between the motor cortex
      controlling muscle pairs. However, these investigations have tended to
      concentrate upon hand muscles. We have extended these investigations to proximal
      muscles that control the scapula upon the trunk and help to move and stabilise
      the shoulder. Using a paired pulse transcranial magnetic stimulation protocol,
      the interhemispheric interactions between different shoulder girdle muscle pairs,
      serratus anterior, upper trapezius and lower trapezius were investigated. Test
      motor evoked potentials were conditioned using conditioning pulse intensities of
      80% and 120% of active motor threshold at three different condition-test
      intervals, during three different tasks. Interhemispheric inhibition was observed
      in upper trapezius using a conditioning intensity of 120% and condition-test
      interval of 8 ms (17 +/- 18%, p < 0.007). A trend towards inhibition was observed
      in lower trapezius and serratus anterior using a conditioning intensity of 120%
      and a condition-test interval of 8 ms (13 +/- 22%; p < 0.07 and 10 +/- 19%
      respectively; p < 0.07). No interhemispheric facilitation was evoked. The study
      demonstrates that a low level of interhemispheric inhibition rather than
      interhemispheric facilitation could be evoked between these muscle pairs.

PMID- 23954023
TI  - Frequency and circumstances of falls in people with inclusion body myositis: a
      questionnaire survey to explore falls management and physiotherapy provision.
AB  - OBJECTIVES: To survey the incidence and circumstances of falls for people with
      inclusion body myositis (IBM) in the UK, and to investigate the provision of
      physiotherapy and falls management. DESIGN: Postal questionnaire survey. SETTING:
      Participants completed questionnaires at home. PARTICIPANTS: Ninety-four people
      diagnosed with IBM were screened against the inclusion criteria. Seventy-two
      potential participants were sent a questionnaire, and 62 were completed and
      returned. Invited participants were sent an adapted Falls Event Questionnaire
      pertaining to falls, perceived causes of falls and the provision of
      physiotherapy. Questionnaires were returned anonymously. MAIN OUTCOME MEASURES:
      The proportions of respondents who reported a fall or a near fall, along with the
      frequencies of falls and near falls were calculated. Descriptive data of falls
      were collected pertaining to location and cause. Data analysis was performed to
      investigate provision of physiotherapy services. RESULTS: The response rate was
      86% [62/72, mean (standard deviation) age 68 (8) years]. Falls were reported by
      98% (61/62) of respondents, with 60% (37/62) falling frequently. In this study,
      age was not found to be an indicator of falls risk or frequency. Twenty-one
      percent (13/62) of respondents had not seen a physiotherapist in relation to
      their IBM symptoms, and of those that had, 31% (15/49) had not seen a
      physiotherapist until more than 12 months after IBM was diagnosed. Only 18%
      (11/61) of fallers reported that they had received falls management input.
      CONCLUSIONS: Falls are a common occurrence for people with IBM, independent of
      age and years since symptoms first presented, and are poorly addressed by
      appropriate physiotherapy management. National falls guidelines are not being
      followed, and referral rates to physiotherapy need to improve.

PMID- 23954024
TI  - Self-managed loaded exercise versus usual physiotherapy treatment for rotator
      cuff tendinopathy: a pilot randomised controlled trial.
AB  - OBJECTIVES: Rotator cuff tendinopathy is a common source of shoulder pain
      characterised by persistent and/or recurrent problems for a proportion of
      sufferers. The aim of this study was to pilot the methods proposed to conduct a
      substantive study to evaluate the effectiveness of a self-managed loaded exercise
      programme versus usual physiotherapy treatment for rotator cuff tendinopathy.
      DESIGN: A single-centre pragmatic unblinded parallel group pilot randomised
      controlled trial. SETTING: One private physiotherapy clinic, northern England.
      PARTICIPANTS: Twenty-four participants with rotator cuff tendinopathy.
      INTERVENTIONS: The intervention was a programme of self-managed loaded exercise.
      The control group received usual physiotherapy treatment. MAIN OUTCOMES: Baseline
      assessment comprised the Shoulder Pain and Disability Index (SPADI) and the Short
      Form 36, repeated three months post randomisation. RESULTS: The recruitment
      target was met and the majority of participants (98%) were willing to be
      randomised. 100% retention was attained with all participants completing the
      SPADI at three months. Exercise adherence rates were excellent (90%). The mean
      change in SPADI score was -23.7 (95% CI -14.4 to -33.3) points for the self
      managed exercise group and -19.0 (95% CI -6.0 to -31.9) points for the usual
      physiotherapy treatment group. The difference in three month SPADI scores was 0.1
      (95% CI -16.6 to 16.9) points in favour of the usual physiotherapy treatment
      group. CONCLUSIONS: In keeping with previous research which indicates the need
      for further evaluation of self-managed loaded exercise for rotator cuff
      tendinopathy, these methods and the preliminary evaluation of outcome offer a
      foundation and stimulus to conduct a substantive study.

PMID- 23954025
TI  - Barriers and facilitators to providing undergraduate physiotherapy clinical
      education in the primary care setting: a three-round Delphi study.
AB  - BACKGROUND: With the global shift in health care from secondary to primary care,
      employment opportunities for newly qualified physiotherapists are likely to be in
      the primary care setting. However, to date, undergraduate physiotherapy clinical
      education has been centred around secondary care, focusing on acute services in
      large teaching hospitals. For contemporary physiotherapists to become effective
      first-contact primary care providers, they need to be exposed to the primary care
      environment during their undergraduate education. OBJECTIVES: To explore the
      concept and identify perceived barriers and facilitators to providing
      physiotherapy undergraduate clinical placements in the primary healthcare setting
      DESIGN: A three-round Delphi survey was used. Participants were asked to answer
      open-ended questions with regard to: (i) student preparation for and (ii)
      provision of primary care placements (Round 1). Content analysis was employed to
      identify key themes. These themes generated statements for Round 2. In Round 2,
      participants were asked to rate their level of agreement/disagreement with the
      generated statements. In Round 3, a final rating process was conducted. Level of
      consensus was established as >=70% agreement, with an interquartile range of <=1.
      PARTICIPANTS: One hundred and ninety-eight primary care physiotherapy staff.
      RESULTS: Barriers identified included shortage of resources (e.g. staff) and a
      lack of tradition; in other words, students are not traditionally educated in the
      primary care setting. Response rates were 60% (120/198), 70% (84/120) and 76%
      (64/84) for Rounds 1, 2 and 3, respectively. All seven key facilitators
      identified reached consensus. They included additional support for staff taking
      students and motivated students. CONCLUSIONS: This study revealed that there is
      support for the provision of physiotherapy clinical education in the primary care
      setting. Through careful consideration with clear planning and collaboration with
      all stakeholders, it may be possible to convert the main barriers identified into
      facilitators to ensure that there will be an adequately prepared physiotherapy
      work force in the future.

PMID- 23954026
TI  - Features of the Japanese national dementia strategy in comparison with
      international dementia policies: How should a national dementia policy interact
      with the public health- and social-care systems?
AB  - BACKGROUND: The Ministry of Health, Labour, and Welfare of the Japanese national
      government announced a "Five-Year Plan for Promotion of Measures Against Dementia
      (Orange Plan)" in September 2012. This article described features of the Japanese
      dementia strategy in comparison with international dementia policies. METHODS: An
      international comparative study was implemented on national dementia policies to
      seek suggestions for Japanese national strategy. The study consisted of a
      bibliographical survey, a field survey, and an online case vignette survey in
      several countries. RESULTS: The Japanese health- and social-care system had
      multiple access points in the dementia care pathway, as did Australia, France,
      South Korea, and the Netherlands. Contrary to Japan, a simplified access point
      was observed in Denmark, England, and Sweden. The Orange Plan aimed to establish
      specific health-care services, social-care services, and the coordination of
      agencies for persons with dementia. However, fragmentation remains in the
      dementia care pathway. CONCLUSION: The national government should examine
      fundamental revisions in health, social-care services, and advocacy in joint
      initiatives with Alzheimer's Association Japan to improve the national dementia
      strategy.

PMID- 23954028
TI  - Blood pressure variability and risk of dementia in an elderly cohort, the Three
      City Study.
AB  - BACKGROUND: The relationship between blood pressure and dementia is incompletely
      understood in elderly individuals. Blood pressure variability may have a role in
      the risk of dementia. METHODS: This investigation was a cohort study of 6506
      elderly individuals followed-up for 8 years (1999-2001 through 2008) with
      assessments at years 2, 4, and 7-8. Blood pressure was measured by electronic
      devices at baseline and at 2- and 4-year follow-up examinations. Cox proportional
      hazard models adjusted for potential confounders were used to estimate the risk
      of incident dementia according to blood pressure (means and coefficients of
      variation of the three measures). RESULTS: During the 40,151 person-years of
      follow-up 474 participants developed dementia. We observed no association between
      mean blood pressure and risk of dementia. In contrast, an increase of 1 standard
      deviation in the coefficient of variation of blood pressure was associated with a
      10% increased risk of dementia. Analysis by deciles of the coefficient of
      variation showed that the higher the variability, the higher the risk of dementia
      (P<.02 for trend). In the fully adjusted Cox model, the risk of dementia for
      those in the highest decile of the coefficient of variation of systolic blood
      pressure was 1.77 (1.17-2.69) compared with the lowest decile. CONCLUSIONS: In
      this cohort study, variability of blood pressure during follow-up was associated
      with an increased risk of incident dementia, whereas mean blood pressure was not.
      Limitation of blood pressure fluctuation may be an important target to preserve
      cognitive function in the elderly.

PMID- 23954027
TI  - Exploration of 100 commonly used drugs and supplements on cognition in older
      adults.
AB  - BACKGROUND: There are conflicting reports and a lack of evidence-based data
      regarding effects of medications on cognition in cognitively normal older adults.
      We explored whether use of 100 common medications taken by older adults is
      associated with longitudinal cognitive performance. METHODS: A longitudinal
      observational cohort was used with analysis of data collected from September 2005
      through May 2011 and maintained in the National Alzheimer's Coordinating Center
      (NACC) Uniform Data Set. Participants were aged 50 years or older and cognitively
      normal (N = 4414). Composite scores were constructed from 10 psychometric tests.
      Scores for each participant reflecting change in the psychometric composite score
      from the baseline clinical assessment to the next assessment were calculated.
      General linear models were used to test whether the mean composite change score
      differed for participants who reported starting, stopping, continuing, or not
      taking each of the 100 most frequently used medications in the NACC sample.
      RESULTS: The average time between assessments was 1.2 years (SD = 0.42). Nine
      medications showed a difference (P < .05) across the four participant groups in
      mean psychometric change scores from the first to the second assessment.
      Medications associated with improved psychometric performance were naproxen,
      calcium-vitamin D, ferrous sulfate, potassium chloride, flax, and sertraline.
      Medications associated with declining psychometric performance were bupropion,
      oxybutynin, and furosemide. CONCLUSIONS: Reported use of common medications is
      associated with cognitive performance in older adults, but studies are needed to
      investigate the mechanisms underlying these effects.

PMID- 23954030
TI  - Temporally precise cell-specific coherence develops in corticostriatal networks
      during learning.
AB  - It has been postulated that selective temporal coordination between neurons and
      development of functional neuronal assemblies are fundamental for brain function
      and behavior. Still, there is little evidence that functionally relevant
      coordination emerges preferentially in neuronal assemblies directly controlling
      behavioral output. We investigated coherence between primary motor cortex and the
      dorsal striatum as rats learn an abstract operant task. Striking coherence
      developed between these regions during learning. Interestingly, coherence was
      selectively increased in cells controlling behavioral output relative to adjacent
      cells. Furthermore, the temporal offset of these interactions aligned closely
      with corticostriatal conduction delays, demonstrating highly precise timing.
      Spikes from either region were followed by a consistent phase in the other,
      suggesting that network feedback reinforces coherence. Together, these results
      demonstrate that temporally precise coherence develops during learning
      specifically in output-relevant neuronal populations and further suggest that
      correlations in oscillatory activity serve to synchronize widespread brain
      networks to produce behavior. 

PMID- 23954032
TI  - The 9th Siena Meeting - from genome to proteome: open innovations.

PMID- 23954029
TI  - Simulating effects of biomarker enrichment on Alzheimer's disease prevention
      trials: conceptual framework and example.
AB  - BACKGROUND: We present a conceptual framework for simulations to determine the
      utility of biomarker enrichment to increase statistical power to detect a
      treatment effect in future Alzheimer's disease prevention trials. We include a
      limited set of simulation results to illustrate aspects of this framework.
      METHODS: We simulated data based on the Alzheimer's Disease Anti-Inflammatory
      Prevention Trial, and a range of sample sizes, biomarker positive predictive
      values, and treatment effects. We also investigated the consequences of assuming
      homogeneity of parameter estimates as a function of dementia outcome. RESULTS:
      Use of biomarkers to increase the sample fraction that would develop Alzheimer's
      disease in the absence of intervention from 0.5 to 0.8 would increase power from
      0.35 to 0.69 with n = 200. Ignoring sample heterogeneity resulted in
      overestimation of power. CONCLUSION: Biomarker enrichment can increase
      statistical power, but estimates of the expected increase are sensitive to a
      variety of assumptions outlined in the framework.

PMID- 23954031
TI  - Distinct basal ganglia circuits controlling behaviors guided by flexible and
      stable values.
AB  - Choosing valuable objects is critical for survival, but their values may change
      flexibly or remain stable. Therefore, animals should be able to update the object
      values flexibly by recent experiences and retain them stably by long-term
      experiences. However, it is unclear how the brain encodes the two conflicting
      forms of values and controls behavior accordingly. We found that distinct
      circuits of the primate caudate nucleus control behavior selectively in the
      flexible and stable value conditions. Single caudate neurons encoded the values
      of visual objects in a regionally distinct manner: flexible value coding in the
      caudate head and stable value coding in the caudate tail. Monkeys adapted in both
      conditions by looking at objects with higher values. Importantly, inactivation of
      each caudate subregion disrupted the high-low value discrimination selectively in
      the flexible or stable context. This parallel complementary mechanism enables
      animals to choose valuable objects in both flexible and stable conditions. 

PMID- 23954033
TI  - Histology-based simulations of ultrasound imaging: methodology.
AB  - Simulations of ultrasound (US) images based on histology may shed light on the
      process by which microscopic tissue features translate to a US image and may
      enable predictions of feature detectability as a function of US system
      parameters. This technical note describes how whole-slide hematoxylin and eosin
      stained histology images can be used to generate maps of fractional change in
      bulk modulus, whose convolution with the impulse response of the US system yields
      simulated US images. The method is illustrated by two canine mastocytoma
      histology images, one with and the other without signs of intra-operative
      hemorrhaging. Quantitative comparisons of the envelope statistics with
      corresponding clinical US images provide preliminary validation of the method.

PMID- 23954034
TI  - Recurrence of glomerulonephritis after renal transplantation.
AB  - Recurrence of glomerulonephritis following renal transplantation is considered an
      important cause of allograft failure. The incidence of recurrence of
      glomerulonephritis varies widely depending on the definition of recurrence
      (pathologic recurrence or clinicopathologic recurrence) and the original
      glomerular disease. Moreover the impact of recurrence of glomerular disease on
      allograft outcome varies widely between different forms of glomerulonephritis.
      Whereas IgA nephritis recurs in up to one third of transplanted patients, this is
      not associated with adverse effects on graft survival. In contrast, recurrent
      focal segmental glomerulosclerosis and membranoproliferative glomerulopathy have
      an unfavorable prognosis. Overall, long-term graft survival in patients
      transplanted for glomerulonephritis is comparable to survival in patients with
      other causes of ESRD. In recent years, several mechanisms for recurrent disease
      after transplantation (e.g. PLA2R antibodies in membranous nephropathy and suPAR
      in FSGS) have been identified, and these findings have helped to elucidate the
      pathogenesis of glomerular diseases. Although renal transplantation is the
      treatment of choice for end-stage renal disease as a consequence of
      glomerulonephritis, further studies are required to develop optimal strategies to
      prevent, diagnose and treat recurrent glomerular diseases. 

PMID- 23954035
TI  - Hormonal changes causing rhinitis in pregnancy among Malaysian women.
AB  - OBJECTIVES: To investigate the aetiology of rhinitis occurring in pregnancy, by
      (1) describing the relationship between pregnancy rhinitis and serum oestrogen,
      progesterone, placental growth hormone and insulin-like growth factor, and (2)
      assessing the prevalence of pregnancy rhinitis among Malaysian women. METHODS:
      Prospective study involving 30 pregnant women followed at an ante-natal clinic
      for 14 months. Hormone levels were analysed during pregnancy and the post-partum
      period. RESULTS: Levels of all four hormones were elevated in the third
      trimester, compared with first trimester and postpartum values. Rhinitis patients
      had higher levels of oestrogen and insulin-like growth factor 1 in the third
      trimester than non-rhinitis patients, although these differences were not
      statistically significant. The prevalence of rhinitis was 53.3 per cent, with
      most cases occurring in the third trimester. Patients with pregnancy rhinitis had
      a higher prevalence of female babies, compared with non-rhinitis patients (p =
      0.003). CONCLUSIONS: Pregnancy rhinitis was significantly more common in women
      giving birth to female babies. Women with pregnancy rhinitis had a non
      significant elevation in oestrogen and insulin-like growth factor 1 levels,
      compared with those without rhinitis.

PMID- 23954036
TI  - Beat the Blues decreases depression in financially strained older African
      American adults.
AB  - OBJECTIVES: Financial strain, defined as inadequate income to cover basic needs,
      is related to depression in minority populations. It is unclear whether
      interventions can improve depression in those reporting financial strain. DESIGN:
      Randomized controlled trial. SETTING: Philadelphia senior center. PARTICIPANTS: A
      total of 208 African-American adults 55 years of age and older with mild to
      severe depressive symptoms. MEASUREMENTS: Beat the Blues (BTB) depression
      intervention, which includes care management, referral/linkage, stress reduction,
      depression education, and behavioral activation. Measurements included responses
      to the Patient Health Questionnaire-9, financial strain, and age. RESULTS:
      Although financial strain was related to depressive symptoms at baseline,
      participants receiving BTB at all levels of financial strain showed reduced
      depressive symptoms compared with a waitlist control group at 4 months. BTB
      participants reporting financial strain had a mean (standard deviation) decrease
      of 6.4 (0.85) points on the Patient Health Questionnaire-9, reflecting a
      clinically meaningful improvement. CONCLUSIONS: This nonpharmacologic
      intervention reduced depressive symptoms in both African-American subjects with
      and without financial strain. However, screening for and helping people manage
      financial strain may boost the magnitude of intervention benefit for those with
      financial strain and should be explored as part of depression care.

PMID- 23954037
TI  - A program to improve detection of undiagnosed dementia in primary care and its
      association with healthcare utilization.
AB  - OBJECTIVE: Alzheimer's disease and related dementias are common and costly, with
      increased healthcare utilization for patients with these disorders. The current
      study describes a novel dementia detection program for veterans and examines
      whether program-eligible patients have higher healthcare utilization than age
      matched comparison patients. DESIGN: Using a telephone-based case-finding
      approach, the detection program used risk factors available in the electronic
      medical record (EMR) and telephone-based brief cognitive screening. Holding
      illness severity constant, dementia detection and healthcare utilization were
      compared across age-matched groups with and without program risk factors.
      SETTING: Five Veterans Affairs Healthcare Network Upstate New York primary care
      clinics. PARTICIPANTS: Veterans aged 70 years and older. MEASUREMENTS: EMR data
      and the Charlson comorbidity index. RESULTS: Program-eligible patients (n =
      5,333) demonstrated significantly greater levels of medical comorbidity relative
      to comparison patients and were on average more than twice as likely to be
      admitted to the hospital. They also had nearly double the number of outpatient
      visits to several services. Similar patterns were seen in those who screened
      positive on a brief cognitive measure, compared with those who screened negative.
      CONCLUSIONS: A novel program using EMR data to assist in the detection of newly
      diagnosed dementia in a clinical setting was found to be useful in identifying
      older veterans with multiple comorbid medical conditions and increased
      utilization of hospital and clinic services. Results suggest undetected cognitive
      impairment and dementia may significantly contribute to healthcare utilization
      and costs of care in older veterans.

PMID- 23954038
TI  - Untangling therapeutic ingredients of a personalized intervention for patients
      with depression and severe COPD.
AB  - OBJECTIVE: We developed a personalized intervention for depressed patients with
      COPD (PID-C) aimed to mobilize patients to participate in the care of both
      conditions. We showed that PID-C reduced depressive symptoms and dyspnea-related
      disability more than usual care over 28 weeks. This study focused on untangling
      key therapeutic ingredients of PID-C. DESIGN: Randomized controlled trial.
      SETTING: Community. PARTICIPANTS: 138 patients who received the diagnoses of COPD
      and major depression after screening 898 consecutive admissions for acute
      inpatient pulmonary rehabilitation. INTERVENTION: Nine sessions of PID-C compared
      with usual care over 28 weeks. MEASUREMENTS: Primary outcome measures were the 17
      item Hamilton Depression Rating Scale and the Pulmonary Functional Status and
      Dyspnea Questionnaire-Modified. Other measures were adherence to rehabilitation
      exercise (>=2 hours per week) and adherence to adequate antidepressant
      prescriptions. RESULTS: Low severity of dyspnea-related disability and adherence
      to antidepressants predicted subsequent improvement of depression. Exercise and
      low depression severity predicted improvement of dyspnea-related disability.
      CONCLUSIONS: PID-C led to an interacting spiral of improvement in both depression
      and disability in a gravely medically ill population with a 17% mortality rate
      over 28 weeks and an expected deterioration in disability. The interrelationship
      of the course of depression and dyspnea-related disability underscores the need
      to target adherence to both antidepressants and chronic obstructive pulmonary
      disease rehabilitation. PID-C may serve as a care management model for depressed
      persons suffering from medical illnesses with a deteriorating course.

PMID- 23954040
TI  - Geriatric anxiety inventory: factor structure and associations with cognitive
      status.
AB  - OBJECTIVES: The factor structure and clinical correlates of the Geriatric Anxiety
      Inventory were determined within a sample of patients with cognitive impairment.
      METHODS: Using a cross-sectional design, data were collected within an outpatient
      Memory Disorders Center. Clinical participants were diagnosed with either mild
      dementia (N = 45) or cognitive impairment, no dementia (N = 55). A comparison
      group of participants without subjective memory complaints (N = 50) was also
      included. The Geriatric Anxiety Inventory was administered and scored as both the
      20-item version and 5-item short form. Measures of cognitive status, depressive
      symptoms, and functioning were also completed. RESULTS: Clinical participants
      reported more severe anxiety than did participants in the comparison group;
      however, the two patient groups did not differ. Principal components analysis
      revealed a four-factor structure of the Geriatric Anxiety Inventory. Item
      endorsement on factors characterized by excessive worry and difficulty making
      decisions were associated with a nearly twofold (odds ratio [OR]: 1.86) and
      nearly sixfold (OR: 5.70) odds of having cognitive impairment, respectively. The
      short-form version was composed of a single factor, and item endorsement was
      associated with a twofold increased odds of having cognitive impairment (OR:
      2.02). CONCLUSION: Psychometric properties of the Geriatric Anxiety Inventory are
      acceptable among patients with cognitive impairment. Anxiety symptoms were
      common, and symptoms characterized by excessive worry and difficulty making
      decisions demonstrated the strongest associations with cognitive status.

PMID- 23954039
TI  - Long-term outcomes of a randomized trial of integrated skills training and
      preventive healthcare for older adults with serious mental illness.
AB  - OBJECTIVE: This report describes 1-, 2-, and 3-year outcomes of a combined
      psychosocial skills training and preventive healthcare intervention (Helping
      Older People Experience Success [HOPES]) for older persons with serious mental
      illness. METHODS: A randomized controlled trial compared HOPES with treatment as
      usual (TAU) for 183 older adults (age >= 50 years [mean age: 60.2]) with serious
      mental illness (28% schizophrenia, 28% schizoaffective disorder, 20% bipolar
      disorder, 24% major depression) from two community mental health centers in
      Boston, Massachusetts, and one in Nashua, New Hampshire. HOPES comprised 12
      months of weekly skills training classes, twice-monthly community practice trips,
      and monthly nurse preventive healthcare visits, followed by a 1-year maintenance
      phase of monthly sessions. Blinded evaluations of functioning, symptoms, and
      service use were conducted at baseline and at a 1-year (end of the intensive
      phase), 2-year (end of the maintenance phase), and 3-year (12 months after the
      intervention) follow-up. RESULTS: HOPES compared with TAU was associated with
      improved community living skills and functioning, greater self-efficacy, lower
      overall psychiatric and negative symptoms, greater acquisition of preventive
      healthcare (more frequent eye exams, visual acuity, hearing tests, mammograms,
      and Pap smears), and nearly twice the rate of completed advance directives. No
      differences were found for medical severity, number of medical conditions,
      subjective health status, or acute service use at the 3-year follow-up.
      CONCLUSION: Skills training and nurse facilitated preventive healthcare for older
      adults with serious mental illness was associated with sustained long-term
      improvement in functioning, symptoms, self-efficacy, preventive healthcare
      screening, and advance care planning.

PMID- 23954041
TI  - A change in sleep pattern may predict Alzheimer disease.
AB  - OBJECTIVE: Sleep problems may adversely affect neuronal health. We examined a
      subjective report of change (reduced duration and/or depth) in sleep pattern in
      relation to subsequent risk of incident all-cause dementia and Alzheimer disease
      (AD) over 9 years. METHODS: This longitudinal study used data from a population
      based sample of 214 Swedish adults aged 75 and over who were dementia-free both
      at baseline and at first follow-up (3 years later). The sample was 80% female
      and, on average, 83.4 years of age at baseline. All participants underwent a
      thorough clinical examination to ascertain all-cause dementia and AD. RESULTS:
      Forty percent of participants reported a change in sleep duration at baseline.
      Between the 6th and 9th year after baseline, 28.5% were diagnosed with all-cause
      dementia, 22.0% of whom had AD. Reduced sleep was associated with a 75% increased
      all-cause dementia risk (hazard ratio: 1.75; 95% confidence interval: 1.04-2.93;
      Wald = 4.55, df = 1, p = 0.035) and double the risk of AD (hazard ratio: 2.01;
      95% confidence interval: 1.12-3.61; Wald = 5.47, df = 1, p = 0.019) after
      adjusting for age, gender, and education. The results remained after adjusting
      for lifestyle and vascular factors but not after adjusting for depressive
      symptoms. No evidence supported a moderating effect of the use of sleeping pills,
      and the sleep-dementia relationship remained after controlling for the presence
      of the apolipoprotein E epsilon4 allele. CONCLUSION: Self-reported sleep problems
      may increase the risk for dementia, and depressive symptoms may explain this
      relationship. Future research should determine whether treatment, in particular,
      behavioral or nonpharmacologic treatment, may represent one avenue toward
      reduction of dementia risk in late life.

PMID- 23954043
TI  - Behavioural effects of directive cues on front-of-package nutrition information:
      the combination matters!
AB  - OBJECTIVE: Nutrition information aims to reduce information asymmetries between
      manufacturers and consumers. To date, however, it remains unclear how nutrition
      information that is shown on the front of the packaging should be designed in
      order to increase both visual attention and the tendency to make healthful food
      choices. The present study aimed to address this gap in research. DESIGN: An
      experimental laboratory study applying mobile eye-tracking technology manipulated
      the presence of two directive cues, i.e. health marks and traffic light colour
      coding, as part of front-of-package nutrition information on actual food
      packages. SETTING: Participants wore mobile eye-tracking glasses during a
      simulated shopping trip. After the ostensible study had finished, they chose one
      snack (from an assortment of fifteen snacks) as a thank you for participation.
      All products were labelled with nutrition information according to the
      experimental condition. SUBJECTS: Consumers (n 160) who were mainly responsible
      for grocery shopping in their household participated in the study. RESULTS: The
      results showed that, in the absence of traffic light colouring, health marks
      reduced attention to the snack food packaging. This effect did not occur when the
      colouring was present. The combination of the two directive cues (v. presenting
      traffic light colours only) made consumers choose more healthful snacks,
      according to the nutrient profile. CONCLUSIONS: Public policy makers may
      recommend retailers and manufacturers implement consistent front-of-pack
      nutrition labelling that contains both health marks and traffic light colouring
      as directive cues. The combination of the cues may increase the likelihood of
      healthful decision making.

PMID- 23954042
TI  - Impact of offspring death on cognitive health in late life: the Cache County
      study.
AB  - OBJECTIVE: Experiencing the death of a child is associated with negative short
      term mental health consequences, but less is known about cognitive outcomes and
      whether such associations extend to late life. We tested the hypothesis that
      experiencing an offspring death (OD) is associated with an increased rate of
      cognitive decline in late life. METHODS: This population-based longitudinal study
      observed four cognitive statuses spaced 3-4 years apart, linked to an extensive
      database containing objective genealogic and vital statistics data. Home visits
      were conducted with 3,174 residents of a rural county in northern Utah, initially
      without dementia, aged 65-105. Cognitive status was measured with the Modified
      Mini-Mental State Exam at baseline and at 3-, 7-, and 10-year follow-ups. OD was
      obtained from the Utah Population Database, which contains statewide birth and
      death records. RESULTS: In linear mixed models, controlling for age, gender,
      education, and apolipoprotein E status, subjects who experienced OD while younger
      than age 31 years experienced a significantly faster rate of cognitive decline in
      late life, but only if they had an epsilon4 allele. Reclassifying all OD
      (regardless of age) according to subsequent birth of another child, OD was only
      related to faster cognitive decline when there were no subsequent births.
      CONCLUSION: Experiencing OD in early adulthood has a long-term association with
      cognitive functioning in late life, with a gene-environment interaction at the
      apolipoprotein E locus. Subsequent birth of another child attenuates this
      association.

PMID- 23954044
TI  - Usefulness of Cochrane Skin Group reviews for clinical practice.
AB  - BACKGROUND AND OBJECTIVE: Systematic reviews are one of the most important
      sources of information for evidence-based medicine. However, there is a general
      impression that these reviews rarely report results that provide sufficient
      evidence to change clinical practice. The aim of this study was to determine the
      percentage of Cochrane Skin Group reviews reporting results with the potential to
      guide clinical decision-making. MATERIAL AND METHODS: We performed a bibliometric
      analysis of all the systematic reviews published by the Cochrane Skin Group up to
      16 August, 2012. We retrieved 55 reviews, which were analyzed and graded
      independently by 2 investigators into 3 categories: 0 (insufficient evidence to
      support or reject the use of an intervention), 1 (insufficient evidence to
      support or reject the use of an intervention but sufficient evidence to support
      recommendations or suggestions), and 2 (sufficient evidence to support or reject
      the use of an intervention). RESULTS: Our analysis showed that 25.5% (14/55) of
      the studies did not provide sufficient evidence to support or reject the use of
      the interventions studied, 45.5% (25/25) provided sufficient but not strong
      evidence to support recommendations or suggestions, and 29.1% (16/55) provided
      strong evidence to support or reject the use of 1 or more of the interventions
      studied. CONCLUSIONS: Most of the systematic reviews published by the Cochrane
      Skin Group provide useful information to improve clinical practice. Clinicians
      should read these reviews and reconsider their current practice.

PMID- 23954045
TI  - Urticaria-like reaction secondary to photodynamic therapy in 2 pediatric
      patients.

PMID- 23954046
TI  - Is bone marrow biopsy always indicated in patients with primary cutaneous
      marginal zone B-cell lymphoma?
AB  - Bone marrow involvement at the time of diagnosis is uncommon in patients with
      primary cutaneous marginal zone B-cell lymphoma (PCMZL). Moreover, in these
      patients such involvement is rarely found in isolation on diagnosis. Typically
      the few patients with PCMZL who have early bone marrow involvement also present
      secondary nodal or visceral involvement, which is detected by other staging
      studies (usually computed tomography). In recent years, this has given rise to
      some debate about whether a bone marrow biopsy should be routinely performed in
      patients diagnosed with PCMZL in view of the good prognosis and low incidence of
      bone marrow infiltration and/or extracutaneous involvement in this type of
      lymphoma. 

PMID- 23954047
TI  - A traumatic corneoscleral epithelial cyst.
AB  - We describe a case of a patient with a corneoscleral epithelial cyst originating
      from a traumatic scleral rupture. Ultrasound biomicroscopy (UBM) and in vivo
      confocal microscopy (IVCM) were used to diagnose this rare condition. A lamellar
      corneoscleral graft was performed with histopathological examination of the
      excised cyst. The treatment of corneoscleral epithelial cysts is discussed. 

PMID- 23954048
TI  - [Systemic conditions associated with central and branch retinal artery
      occlusions].
AB  - INTRODUCTION: Retinal artery occlusions (RAO) are severe conditions threatening
      vision, affecting the subsequent mortality of these patients. PATIENTS AND
      METHODS: We retrospectively reviewed the work-up performed in all patients
      diagnosed with retinal artery occlusions evaluated in two university hospitals in
      France (Tours and Angers). RESULTS: A total of 131 patients (131 eyes) with RAO
      were included, with a mean age of 69.5years and male predominance (64 %). Central
      retinal artery occlusion (CRAO) resulted in poor initial visual acuity (90 % less
      than count fingers), whereas those with branch retinal artery occlusion (BRAO)
      had better visual acuity (63.6 % better than 20/40). Systemic arterial
      hypertension (HTN) was the most common associated risk factor. Carotid stenosis
      was found in 50 % of cases, leading to endarterectomy in nine patients (6.9 %),
      while an underlying cardiac cause was implicated in 14 % of cases. Giant cell
      arteritis was diagnosed in five patients (3.8 %). DISCUSSION: Work-up of RAO may
      detect treatable cardiovascular and systemic conditions, allowing prevention of
      further ocular recurrence or stroke. CONCLUSION: Etiologic work-up of retinal
      arterial occlusion can diagnose potentially treatable underlying systemic
      conditions, such as giant cell arteritis, cardiac conditions and extracranial
      cerebrovascular disease. Giant cell arteritis has to be ruled out at the acute
      phase, while the role and timing of semi-urgent testing (supra-aortic Doppler
      echography, echocardiography, electrocardiography, lab work-up) or delayed
      testing (transesophageal echocardiography, brain imaging) have yet to be
      determined.

PMID- 23954049
TI  - First person: a mental health mission to post-earthquake El Salvador.
AB  - In this article the author excerpts and discusses salient quotes or moments from
      the journal he compiled while visiting El Salvador in February 2001 as head of
      Disaster Psychiatry Outreach (DPO) to assist survivors of a major earthquake.
      This case discussion of a single disaster mental health response exemplifies key
      issues related to both short and long term mental health service delivery to
      disaster affected communities. 

PMID- 23954050
TI  - Recent disasters in Sri Lanka: lessons learned.
AB  - Sri Lanka has faced several disasters in the recent past, both manmade and
      natural. The mental health and psychosocial consequences have been felt at the
      individual, family, and collective levels. Individuals developed normal distress,
      posttraumatic stress disorder, depression, or alcohol abuse. There were changes
      in family and social processes causing a tearing of the social fabric, lack of
      social cohesion, disconnection, mistrust, hopelessness, dependency, lack of
      motivation, powerlessness, and despondency. Because of the widespread nature of
      mental health needs, a community approach would reach the most number of people. 

PMID- 23954051
TI  - The psychological and psychiatric effects of terrorism: lessons from London.
AB  - The 7 July 2005 bombings in London caused heightened levels of distress among
      some in the general community. This distress was most notable in Muslims and
      members of ethnic minority groups. These effects were transient for most. An
      estimated 30% of those who were more affected by the attacks, including victims
      and witnesses, developed psychiatric disorders as a result. An outreach program
      was set up to screen those who were exposed to potentially traumatic events and
      to offer them evidence-based treatment. This article discusses what lessons might
      be learned from studies of the general community and the screen-and-treat
      approach. 

PMID- 23954052
TI  - The Great East Japan Earthquake, tsunami, and Fukushima Daiichi nuclear power
      plant accident: a triple disaster affecting the mental health of the country.
AB  - The Great East Japan Earthquake in 2011 caused 2 other serious disasters: a
      tsunami and a nuclear power plant accident. A chronic shortage of mental health
      resources had been previously reported in the Tohoku region, and the triple
      disaster worsened the situation. Eventually a public health approach was
      implemented by providing a common room in temporary housing developments to build
      a sense of community and to approach evacuees so that they could be triaged and
      referred to mental health teams. Japan now advocates using psychological first
      aid to educate first responders. This article extracts key lessons from relevant
      literature. 

PMID- 23954053
TI  - Hurricane Katrina and the Gulf oil spill: lessons learned.
AB  - Education and training about immediate responses are important for all mental
      health providers of immediate and continuing services to assist children,
      adolescents, adults, and families in the aftermath of disasters. To sensitively
      help with evacuations and return to normalcy, responders must also be trained to
      understand the culture and traditions of affected communities. It is important to
      provide knowledge about available resources and to emphasize the need for
      routines and self-care for both victims and responders in an environment that,
      with recovery, will reflect a new normal. 

PMID- 23954054
TI  - The perspective of psychosocial support a decade after Bam earthquake:
      achievements and challenges.
AB  - The 2003 Bam earthquake was one of the most catastrophic disasters to have struck
      Iran. This article summarizes the short-term and long-term psychological, social,
      and economic impacts of the Bam earthquake on survivors across a decade since its
      occurrence. Identification and definition of capability as well as recognizing
      the nature and extent of personal and social capabilities in a community are
      priceless in preventing disasters and reducing their consequent destruction. 

PMID- 23954055
TI  - Holistic approach to community in crisis.
AB  - This report emphasizes the belief that whatever the type and scale of disaster,
      the period of transition from relief to recovery is the most critical. Following
      the severe earthquake that struck Kachchh, Gurjarat, India on 26 January 2001,
      emotions spanned grief over the lives lost; anxiety over property and other
      economic losses; profound feelings of isolation, helplessness, and guilt; and
      panic in the face of problematic communications from authorities. In an attempt
      to manage this vast array of psychosocial problems, a large cadre of volunteers
      was rapidly trained and supervised by experts to work as grass-roots counselors
      for the community. 

PMID- 23954056
TI  - The enduring mental health impact of the September 11th terrorist attacks:
      challenges and lessons learned.
AB  - The authors review the existing literature on the mental health impact of the
      September 11th attacks and the implications for disaster mental health clinicians
      and policy makers. The authors discuss the demographic characteristics of those
      affected and the state of mental health needs and existing mental health delivery
      services; the nature of the disaster and primary impacts on lives,
      infrastructure, and socioeconomic factors; the acute aftermath in the days and
      weeks after the attacks; the persistent mental health impact and evolution of
      services of the postacute aftermath; and the implications for future disaster
      mental health practitioners and policy makers. 

PMID- 23954057
TI  - The 2010 Haiti earthquake response.
AB  - This article presents an overview of the mental health response to the 2010 Haiti
      earthquake. Discussion includes consideration of complexities that relate to
      emergency response, mental health and psychosocial response in disasters, long
      term planning of systems of care, and the development of safe, effective, and
      culturally sound mental health services in the Haitian context. This information
      will be of value to mental health professionals and policy specialists interested
      in mental health in Haiti, and in the delivery of mental health services in
      particularly resource-limited contexts in the setting of disasters. 

PMID- 23954059
TI  - Disasters: a global perspective.

PMID- 23954058
TI  - Community engagement in disaster preparedness and recovery: a tale of two cities-
      Los Angeles and New Orleans.
AB  - Awareness of the impact of disasters globally on mental health is increasing.
      Known difficulties in preparing communities for disasters and a lack of focus on
      relationship building and organizational capacity in preparedness and response
      have led to a greater policy focus on community resiliency as a key public health
      approach to disaster response. In this article, the authors describe how an
      approach to community engagement for improving mental health services, disaster
      recovery, and preparedness from a community resiliency perspective emerged from
      their work in applying a partnered, participatory research framework,
      iteratively, in Los Angeles County and the City of New Orleans. 

PMID- 23954060
TI  - Automated 3-dimensional aortic annular assessment by multidetector computed
      tomography in transcatheter aortic valve implantation.
AB  - OBJECTIVES: This study sought to evaluate the accuracy, reproducibility, and
      predictive value for post-procedural aortic regurgitation (AR) of an automated
      multidetector computed tomography (MDCT) post-processing imaging software,
      3mensio Valves (version 5.1.sp1, 3mensio Medical Imaging BV, the Netherlands), in
      the assessment of patients undergoing transcatheter aortic valve implantation
      (TAVI). BACKGROUND: Accurate pre-operative aortic annulus measurements are
      crucial for patients undergoing TAVI. METHODS: One hundred five patients
      undergoing MDCT screening before TAVI were evaluated. Aortic annular measurement
      was compared between automated 3mensio Valves software and manual data post
      processing software on a dedicated workstation; we analyzed the discrimination
      value of annulus measurement for post-procedural AR in 44 recipients of a self
      expanding valve. RESULTS: The automated 3mensio Valves software showed good
      concordance with manual MDCT measurements as demonstrated by Bland-Altman
      analysis. The automated software provided equally good reproducibility as manual
      measurement, especially for measurement of aortic annulus area (intraobserver
      intraclass correlation coefficients 0.98 vs. 0.97, interobserver 0.98 vs. 0.95).
      In 44 patients after implantation of a self-expanding valve, the valve
      diameter/CT-measured geometric mean annulus diameter ratio by automated 3mensio
      Valves software showed moderate and better discrimination ability in predicting
      post-procedural AR compared with manual measurement (p = 0.12, area under the
      curve 0.77, 95% confidence interval: 0.63 to 0.91, area under the curve 0.68, 95%
      confidence interval: 0.50 to 0.86, respectively). CONCLUSIONS: The automated
      3mensio Valves software demonstrated reliable, reproducible aortic annulus
      measurement and better predictive value for post-procedural AR, suggesting
      important clinical implications for pre-operative assessment of patients
      undergoing TAVI.

PMID- 23954061
TI  - Elevated levels of systemic pentraxin 3 are associated with thin-cap
      fibroatheroma in coronary culprit lesions: assessment by optical coherence
      tomography and intravascular ultrasound.
AB  - OBJECTIVES: This study sought to determine whether systemic levels of pentraxin 3
      (PTX3), a novel inflammatory marker, are associated with thin-cap fibroatheroma
      (TCFA). BACKGROUND: Biomarkers predicting the presence of TCFA in vivo have not
      been established. METHODS: We evaluated 75 patients (stable angina pectoris, n =
      47; acute coronary syndrome, n = 28) with de novo culprit lesions who were
      examined by optical coherence tomography and intravascular ultrasound. We defined
      TCFA as lipid-rich plaque with a fibrous cap <65 MUm thick. Systemic levels of
      PTX3 were compared between patients with and without TCFA. RESULTS: Thirty-eight
      and 37 patients with and without TCFA, respectively, were identified. Levels of
      PTX3 were significantly higher in patients with than in those without TCFA (p <
      0.001) and correlated inversely with fibrous cap thickness (r = -0.71, p = 0.001)
      and positively with the remodeling index (r = 0.25, p = 0.037). Multivariate
      logistic regression analysis showed that a higher PTX3 level was the most
      powerful predictor of TCFA (odds ratio: 3.26, 95% confidence interval: 1.75 to
      6.05, p < 0.001). Receiver-operating characteristic curve analysis showed that
      >3.24 ng/ml of PTX3 could predict TCFA with 84% sensitivity and 86% specificity.
      CONCLUSIONS: Higher levels of systemic PTX3 are associated with TCFA. Systemic
      PTX3 levels comprise a useful inflammatory marker that reflects coronary plaque
      vulnerability.

PMID- 23954062
TI  - Impact of kissing balloon inflation on the main vessel stent volume, area, and
      symmetry after side-branch dilation in patients with coronary bifurcation
      lesions: a serial volumetric intravascular ultrasound study.
AB  - OBJECTIVES: Intravascular ultrasound (IVUS) was performed to investigate the
      impact of kissing balloon inflation (KBI) on the main vessel (MV) stent volume,
      area, and symmetry after side-branch (SB) dilation in patients with coronary
      bifurcation lesions (CBL). BACKGROUND: It remains controversial whether KBI would
      restore the MV stent area and symmetry loss after SB dilation. METHODS: A total
      of 88 serial IVUS examinations of the MV were performed after MV angioplasty, MV
      stenting, SB dilation, and KBI in 22 patients with CBL. The MV stent was divided
      into proximal, bifurcation, and distal segments; the stent volume index (SVI),
      minimal stent area (MSA), stent symmetry index (SSI), and external elastic
      membrane (EEM) volume index were measured in 198 stent segments and compared
      after MV stenting, SB dilation, and KBI. RESULTS: In the bifurcation segment,
      SVI, MSA, and SSI were significantly smaller after SB dilation than after MV
      stenting and KBI (SVI was 6.10 +/- 1.50 mm(3)/mm vs. 6.68 +/- 1.60 mm(3)/mm and
      6.57 +/- 1.60 mm(3)/mm, respectively, p < 0.05; MSA was 5.15 +/- 1.30 mm(2) vs.
      6.08 +/- 1.40 mm(2) and 5.86 +/- 1.50 mm(2), respectively, p < 0.05; and SSI was
      0.78 +/- 0.02 mm(2) vs. 0.87 +/- 0.03 mm(2) and 0.84 +/- 0.03 mm(2),
      respectively, p < 0.05). KBI restored the MV SVI, MSA, and SSI after SB dilation.
      In the proximal segment, SVI, MSA, and EEM volume index were significantly
      larger, but SSI was smaller after KBI than after MV stenting and SB dilation. In
      the distal segment, neither SB dilation nor KBI had a significant impact on the
      MV stent volume or symmetry. CONCLUSIONS: This is the first comprehensive
      volumetric IVUS analysis of CBL, to our knowledge, demonstrating that KBI
      restores the MV stent volume, area, and symmetry loss after SB dilation in the
      bifurcation segment, and induces asymmetric stent expansion in the proximal
      segment.

PMID- 23954063
TI  - Clinical outcomes of the Resolute zotarolimus-eluting stent in patients with in
      stent restenosis: 2-year results from a pooled analysis.
AB  - OBJECTIVES: This study sought to assess the clinical safety and effectiveness of
      the Resolute zotarolimus-eluting stent (R-ZES) in patients with in-stent
      restenosis (ISR) from 2 large trials. BACKGROUND: ISR treatment is associated
      with higher rates of subsequent cardiac events compared with treatment of de novo
      lesions. Although drug-eluting stents (DES) are an option, second-generation DES
      are largely untested in the treatment of ISR. METHODS: A total of 3,489 patients
      were pooled from the RAC (RESOLUTE All Comers) trial and the RESOLUTE
      International (RINT) registry. Two-year clinical endpoints included clinically
      driven target lesion revascularization (TLR), target lesion failure (TLF),
      cardiac death (CD), target vessel myocardial infarction (TVMI), combined CD or
      TVMI (CD/TVMI), and Academic Research Consortium definite and probable stent
      thrombosis (ST). RESULTS: Overall, 281 patients (8.1%) received an R-ZES for ISR.
      Two-year TLR and TLF rates were significantly higher in ISR patients than in non
      ISR patients (TLR: 12.7% vs. 4.3%, p = 0.003; TLF: 17.4% vs. 9.4%, p = 0.007);
      however, the CD/TVMI rate was not (6.9% vs. 6.1%, p = 0.711). Seven ISR patients
      had ST. Two-year outcomes by ISR stent type were similar: bare-metal stent (BMS)
      ISR TLR was 12.5% and TLF was 17.2%; DES-ISR TLR was 13.0% and TLF was 18.8%.
      CD/TVMI was 7.3% and 7.2% for BMS-ISR and DES-ISR, respectively. CONCLUSIONS:
      Using R-ZES to treat ISR appears equally safe in BMS-ISR and DES-ISR, with
      CD/TVMI rates comparable to 2-year outcomes in other clinical trials. Although
      revascularization rates are still higher in ISR lesions, the R-ZES offers an
      effective alternative for treatment of BMS-ISR and DES-ISR. (Randomized, Two-Arm,
      Non-inferiority Study Comparing Endeavor-Resolute Stent With Abbot Xience-V Stent
      [RESOLUTE-AC]; NCT00617084; and RESOLUTE International Registry: Evaluation of
      the Resolute Zotarolimus-Eluting Stent System in a 'Real-World' Patient
      Population [RINT]; NCT00752128).

PMID- 23954064
TI  - Potential entrapment of an accessory superficial peroneal sensory nerve at the
      lateral malleolus: a cadaveric case report and review of the literature.
AB  - The superficial peroneal nerve presents great anatomic variability regarding its
      emergence from the crural fascia, course, branching pattern, and distribution
      area. Entrapment neuropathy of the superficial peroneal nerve has been documented
      in the published data, resulting in pain and paresthesia over the dorsum of the
      foot. We report a case of a female cadaver in which an accessory superficial
      peroneal sensory nerve was encountered. The nerve originated from the main
      superficial peroneal nerve trunk, proximal to the superficial peroneal nerve
      emergence from the crural fascia, and followed a subfascial course. After fascial
      penetration, the supernumerary nerve was distributed to the skin of the proximal
      dorsum of the foot and lateral malleolar area. A potential entrapment site of the
      nerve was observed at the lateral malleolar area, because the accessory nerve
      traveled through a fascial tunnel while perforating the crural fascia, and
      presented with distinct post-stenotic enlargement at its exit point. The likely
      presence of such a very rare variant and its potential entrapment is essential
      for the physician and surgeon to establish a correct diagnosis and avoid
      complications during procedures to the foot and ankle region. 

PMID- 23954065
TI  - Outbreak of ertapenem-resistant Enterobacter cloacae urinary tract infections due
      to a contaminated ureteroscope.
AB  - BACKGROUND: Outbreaks of urinary tract infections (UTIs) due to contaminated
      ureteroscopes have been rarely reported. AIM: To report such an outbreak at a
      regional teaching hospital in southern Taiwan. METHODS: From October to December
      2010, ertapenem-resistant Enterobacter cloacae were identified from urine
      cultures of 15 patients who had undergone ureteroscopy prior to the infection.
      Three batches of surveillance cultures were obtained from the environmental
      objects and healthcare workers related to the procedures. Pulsed-field gel
      electrophoresis (PFGE) was used for bacterial typing. Antimicrobial
      susceptibility was assessed by disc diffusion and E-test methods. Polymerase
      chain reaction and sequencing were used to analyse beta-lactamase genes.
      FINDINGS: A total of 70 specimens were obtained during the first surveillance
      operation. One ertapenem-resistant E. cloacae was isolated from a ureteroscope.
      Although the disinfection protocols for ureteroscopes were revised and
      implemented, seven additional UTI cases were identified thereafter. The pathogen
      was identified from two subsequent surveillance cultures and was not eliminated
      until ethylene oxide sterilization was added to the disinfection protocol. PFGE
      revealed that all 15 isolates from the patients and the three isolates from the
      ureteroscope shared a common pattern with minor variance. Most isolates were
      resistant to gentamicin, levofloxacin, ceftriaxone, ceftazidime, and ertapenem.
      All isolates were susceptible to amikacin, imipenem, and meropenem. SHV-12 and
      IMP-8 genes were simultaneously identified in 16 of the 18 isolates. CONCLUSION:
      The outbreak of ertapenem-resistant E. cloacae was caused by a contaminated
      ureteroscope and was terminated by the implementation of a revised disinfection
      protocol for ureteroscopes.

PMID- 23954066
TI  - Influence of hydronium, sulfate, chloride and other non-carbonate ions on
      hydrogen generation by anaerobic corrosion of granular cast iron.
AB  - Permeable reactive barriers are successfully applied for the removal of various
      contaminants. The concomitant reduction of hydrogen ions and the subsequent
      formation of hydrogen gas by anaerobic corrosion lead to decreased pore volume
      filled with water and thus residence times, so called gas clogging. Long term
      column experiments were conducted to elucidate the impact of ubiquitous water
      constituents on the formation of hydrogen gas and potential passivation due to
      corrosion products. The collected gas volumes revealed a relation to the
      hydronium concentration (pH) but were only slightly increased in the presence of
      chloride and sulfate and not significantly influenced in the presence of
      phosphate, silicate, humic acid and ammonium compared to deionized water.
      Significant gas volumes within the reactive filling were verified by gravimetry.
      The presence of nitrate completely eliminated hydrogen formation by competition
      for electrons. Solid phase analyses revealed that neither chloride nor sulfate
      was incorporated in corrosion products in concentrations above 0.1 weight
      percent, and they did not alter the formation of mainly magnetite in comparison
      to deionized water. 

PMID- 23954067
TI  - Multistage treatment system for raw leachate from sanitary landfill combining
      biological nitrification-denitrification/solar photo-Fenton/biological processes,
      at a scale close to industrial--biodegradability enhancement and evolution
      profile of trace pollutants.
AB  - A multistage treatment system, at a scale close to the industrial, was designed
      for the treatment of a mature raw landfill leachate, including: a) an activated
      sludge biological oxidation (ASBO), under aerobic and anoxic conditions; b) a
      solar photo-Fenton process, enhancing the bio-treated leachate biodegradability,
      with and without sludge removal after acidification; and c) a final polishing
      step, with further ASBO. The raw leachate was characterized by a high
      concentration of humic substances (HS) (1211 mg CHS/L), representing 39% of the
      dissolved organic carbon (DOC) content, and a high nitrogen content, mainly in
      the form of ammonium nitrogen (>3.8 g NH4(+)-N/L). In the first biological
      oxidation step, a 95% removal of total nitrogen and a 39% mineralization in terms
      of DOC were achieved, remaining only the recalcitrant fraction, mainly attributed
      to HS (57% of DOC). Under aerobic conditions, the highest nitrification rate
      obtained was 8.2 mg NH4(+)-N/h/g of volatile suspended solids (VSS), and under
      anoxic conditions, the maximum denitrification rate obtained was 5.8 mg (NO2(-)-N
      + NO3(-)-N)/h/g VSS, with a C/N consumption ratio of 2.4 mg CH3OH/mg (NO2(-)-N +
      NO3(-)-N). The precipitation of humic acids (37% of HS) after acidification of
      the bio-treated leachate corresponds to a 96% DOC abatement. The amount of UV
      energy and H2O2 consumption during the photo-Fenton reaction was 30% higher in
      the experiment without sludge removal and, consequently, the reaction velocity
      was 30% lower. The phototreatment process led to the depletion of HS >80%, of low
      molecular-weight carboxylate anions >70% and other organic micropollutants, thus
      resulting in a total biodegradability increase of >70%. The second biological
      oxidation allowed to obtain a final treated leachate in compliance with legal
      discharge limits regarding water bodies (with the exception of sulfate ions),
      considering the experiment without sludge. Finally, the high efficiency of the
      overall treatment process was further reinforced by the total removal percentages
      attained for the identified organic trace contaminants (>90%).

PMID- 23954068
TI  - Stormwater quality performance of a macro-pervious pavement car park installation
      equipped with channel drain based oil and silt retention devices.
AB  - This paper reports the results of a two year field monitoring exercise intended
      to investigate the pollution abatement capabilities of a novel system which
      offers an alternative to the, now well established, pervious pavement system as a
      source control device for stormwater management. The aim of this study was to
      determine the effectiveness of a live installation of a macro-pervious pavement
      system (MPPS) (operated as a visitors' car park at a prison in Central Scotland)
      in retaining and treating a range of pollutants which originate from automobile
      use or become concentrated on the parking surface from the wider environment. The
      MPPS is a sub-class of pervious pavement system where the vast majority of the
      surface is impermeable. It directs stormwater into a pervious sub surface
      storage/attenuation zone through a series of distinct infiltration points fast
      enough to prevent flooding during the design storm. In the particular system
      studied here the infiltration points consist of a network of oil/silt separation
      devices with extensive further pollutant retention/degradation provided during
      the passage of stormwater through the sub surface zone. Approximately 12 months
      after the car park was completed a sampling regime was instigated in which grab
      samples were collected at intervals from each of the three sub catchments whilst,
      simultaneously, samples were collected directly from the, pollutant retaining,
      infiltration devices. Through investigation of samples collected at the upstream
      end of the system, the retention of significant amounts of hydrocarbons and heavy
      metals in the initial collection devices has been illustrated and the analysis of
      effluent samples collected at the outlet points indicate that the system is
      capable of producing effluent which is of a standard comparable to that expected
      from a traditional pervious pavement system and is acceptable for direct release
      into a surface water receptor. The system offers the opportunity to accrue the
      benefits of a pervious pavement when the use of traditional paving surfaces is
      the preferred option. 

PMID- 23954069
TI  - The adjuvant use of lansoprazole, clonazepam and dimenhydrinate for treating
      intractable hiccups in a patient with gastritis and reflux esophagitis
      complicated with myocardial infarction: a case report.
AB  - BACKGROUND: Hiccup (Singultus) is a sudden and involuntary contraction of the
      diaphragm followed by a sharp closure of the epiglottis which results in the
      production of a specific "hic" sound. Normally, hiccups are treated without
      intervention. Intractable hiccups occur rarely but are a disturbing symptom
      underlying other health related disorders. CASE PRESENTATION: We report the
      clinical case of a 67-year-old male patient with myocardial infarction
      accompanied by intractable hiccups during the course of 8 months, and who was non
      responsive to chlorpromazine or metoclopramide, and baclofen; drugs routinely
      used to treat this condition. This sustained hiccup had severely restricted the
      patient's ability to intake food and sleep. To explore alternative treatments, we
      investigated the adjuvant administration of lansoprazole, dimenhydrinate and
      clonazepam in this patient. We discovered that this drug combination was capable
      of successfully terminating his intractable hiccups, with no further evidence of
      recurrence. No similar treatment is previously reported for intractable hiccups.
      We further suggest a hypothesis concerning a potential mechanism on the anti
      hiccup effect of dimenhydrinate. CONCLUSION: We identified that the adjuvant use
      of lansoprazole, clonazepam and dimenhydrinate was capable of attenuating the
      symptoms of our patient with intractable hiccups.

PMID- 23954070
TI  - Redressing the epidemics of opioid overdose and HIV among people who inject drugs
      in Central Asia: the need for a syndemic approach.
AB  - BACKGROUND: Accumulating evidence suggests that opioid overdose and HIV infection
      are burgeoning intertwined epidemics among people who inject drugs (PWID) in
      Central Asia. To date, however, research on overdose and its associations with
      HIV risks among PWID in Central Asia remains virtually absent. This paper aims to
      provide a regional overview of the hidden epidemic of overdose and how it is
      linked to HIV among PWID in Central Asia, using a syndemic framework that is
      guided by risk environment research. METHODS: We conducted a comprehensive
      literature search of peer-reviewed publications and gray literature on opioid
      overdose and its associations with HIV in five countries of Central Asia
      (Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan and Uzbekistan) as well as on
      policies and programs that address these co-occurring epidemics. RESULTS:
      Regional data indicate high rates of fatal and non-fatal overdose among PWID.
      Evidence suggests mortality rates from overdose exceed HIV/AIDS as the leading
      cause of death among PWID. The syndemic framework suggests multiple macro-level
      and micro-level environmental risk factors that drive the co-occurring epidemics
      of HIV and overdose. This framework identifies several interacting biological and
      behavioral risks that result in additive effects for HIV and overdose.
      CONCLUSION: The high rates of overdose and its associations with HIV underscore
      the need for a syndemic approach that considers overdose on parity with HIV. Such
      an approach should focus on the biological, behavioral and structural
      interactions between these epidemics to reduce social suffering, morbidity and
      mortality among PWID in Central Asia.

PMID- 23954071
TI  - Understanding the role of cessation fatigue in the smoking cessation process.
AB  - BACKGROUND: To understand the dynamic process of cessation fatigue (i.e., the
      tiredness of trying to quit smoking) with respect to its average trend, effect on
      relapse, time-varying relations with craving and negative affect, and differences
      among genders and treatment groups. METHOD: Randomized placebo-controlled
      clinical trial. Participants received either placebo, monotherapy (bupropion SR,
      nicotine patch, nicotine lozenge), or combined pharmacotherapy (bupropion
      SR+nicotine lozenge, nicotine patch+nicotine lozenge). Data were collected from
      1504 daily smokers who were motivated to quit smoking. The participants completed
      baseline assessments and ecological momentary assessments for 2 weeks post-quit.
      RESULTS: Cessation fatigue reduced the likelihood of 6-month post-quit abstinence
      (OR=0.97, 95% CI (0.95, 0.99)), and was positively associated with craving and
      negative affect. After controlling for these two factors, average cessation
      fatigue increased over time. Compared to men, women experienced greater fatigue
      (t=-10.69, p<0.0001) and a stronger relation between fatigue and craving (t=
      8.80, p<0.0001). The relationship between fatigue and negative affect was
      significantly stronger in men (t=5.73, p<0.0001). Cessation fatigue was
      significantly reduced by combined pharmacotherapy (t=-13.4, p<0.0001), as well as
      monotherapy (t=-6.2, p<0.0001). CONCLUSIONS: Cessation fatigue was closely
      related to craving, negative affect, and cessation outcomes. Women reported
      greater cessation fatigue than men. Current treatments appeared to reduce fatigue
      and weaken its relations with craving and negative affect.

PMID- 23954072
TI  - HIV among female sex workers in the Central Asian Republics, Afghanistan, and
      Mongolia: contexts and convergence with drug use.
AB  - BACKGROUND: Central Asia is culturally and demographically diverse, both between
      and within its respective countries. That diversity is represented in the range
      of individual, network, community, and structural risks for female sex workers
      (FSWs) regionally. FSWs have several risk factors for HIV acquisition and
      transmission including behavioral, biological, and structural risk factors.
      Across Central Asia, sexual risks have become conflated with risks associated
      with injection and non-injection illicit drug use. METHODS: Peer-reviewed
      literature databases and gray literature were searched for articles on sex work
      in Central Asia. The medial subject heading (MeSH) of "sex work" was cross
      referenced with terms associated with Uzbekistan, Tajikistan, Turkmenistan,
      Kazakhstan, Kyrgyzstan, Mongolia, and Afghanistan. RESULTS: HIV prevalence data
      for FSWs suggest sustained or increasing prevalence in the region. There are
      increasing data directly linking HIV among FSWs to injection drug use; odds of
      HIV are up to 20 times higher among FSWs reporting injecting drug use. Though
      injecting drug use among FSWs is rare in some settings, recreational drugs and
      alcohol use limits other risk reduction behaviors, such as condom use.
      CONCLUSIONS: The Central Asian HIV epidemic has traditionally been assumed to be
      driven nearly exclusively by drug use, resulting in surveillance systems focused
      on parenteral transmission. The reviewed data highlight limited attention to
      characterizing the burden of HIV and risk factors for HIV acquisition and
      transmission among FSWs who use drugs. Moving forward will require enhanced HIV
      surveillance and research to inform HIV prevention approaches to address all
      levels of HIV risks affecting FSWs in Central Asia.

PMID- 23954073
TI  - Pentasaccharide resin glycosides from Ipomoea cairica and their cytotoxic
      activities.
AB  - Six partially acylated pentasaccharide resin glycosides, cairicosides A-F, were
      isolated from the aerial parts of Ipomoea cairica. These compounds were
      characterized as a group of macrolactones of simonic acid A, partially acylated
      with different organic acids. The lactonization site of 11S-hydroxyhexadecanoic
      acid (jalapinolic acid) was bound to the second saccharide moiety at C-3 in
      cairicosides A-E, while at C-2 in cairicoside F. Structures were established by
      spectroscopic and chemical methods. Compounds cairicosides A-E exhibited moderate
      cytotoxicity against a small panel of human tumor cell lines with IC50 values in
      the range of 4.28-14.31MUM. 

PMID- 23954074
TI  - Eudesmane-type sesquiterpene derivatives from Laggera alata.
AB  - Ten eudesmane-type sesquiterpene derivatives (1-10), including six cuauhtemone
      derivatives (1-6), one di-norsesquiterpene (3-oxo-di-nor-eudesma-4-en-11-oic
      acid, 7), and three eudesmane glycosides (alatoside F-H, 8-10) were isolated from
      the whole plants of Laggera alata together with 12 known compounds. Their
      structures were elucidated on the basis of extensive spectroscopic analysis, acid
      hydrolysis, and compounds 1 and 7 were studied by single-crystal X-ray
      diffraction analysis. The absolute configuration of 1 was determined by the
      application of the modified Mosher's method. All of the isolated eudesmane-type
      sesquiterpenes were evaluated for their cytotoxic activities on six human cancer
      cell lines, but all of the compounds were inactive on the tested cell lines in
      the concentration of 100 MUg/mL.

PMID- 23954075
TI  - Biosynthesis of sesquiterpenes in grape berry exocarp of Vitis vinifera L.:
      evidence for a transport of farnesyl diphosphate precursors from plastids to the
      cytosol.
AB  - The participation of the mevalonic acid (MVA) and 1-deoxy-d-xylulose 5
      phosphate/2-C-methyl-d-erythritol-4-phosphate (DOXP/MEP) pathways in
      sesquiterpene biosynthesis of grape berries was investigated. There is an
      increasing interest in this class of terpenoids, since the oxygenated
      sesquiterpene rotundone was identified as the peppery aroma impact compound in
      Australian Shiraz wines. To investigate precursor supply pathway utilization, in
      vivo feeding experiments were performed with the deuterium labeled, pathway
      specific, precursors [5,5-(2)H2]-1-deoxy-d-xylulose and [5,5-(2)H2]-mevalonic
      acid lactone. Head Space-Solid Phase Micro Extraction-Gas Chromatography-Mass
      Spectrometry (HS-SPME-GC-MS) analysis of the generated volatile metabolites
      demonstrated that de novo sesquiterpene biosynthesis is mainly located in the
      grape berry exocarp (skin), with no detectable activity in the mesocarp (flesh)
      of the Lemberger variety. Interestingly, precursors from both the (primarily)
      cytosolic MVA and plastidial DOXP/MEP pathways were incorporated into grape
      sesquiterpenes in the varieties Lemberger, Gewurztraminer and Syrah. Our labeling
      data provide evidence for a homogenous, cytosolic pool of precursors for
      sesquiterpene biosynthesis, indicating that a transport of precursors occurs
      mostly from plastids to the cytosol. The labeling patterns of the sesquiterpene
      germacrene D were in agreement with a cyclization mechanism analogous to that of
      a previously cloned enantioselective (R)-germacrene D synthase from Solidago
      canadensis. This observation was subsequently confirmed by enantioselective GC-MS
      analysis demonstrating the exclusive presence of (R)-germacrene D, and not the
      (S)-enantiomer, in grape berries. 

PMID- 23954076
TI  - Ceriponols A-K, tremulane sesquitepenes from Ceriporia lacerate HS-ZJUT-C13A, a
      fungal endophyte of Huperzia serrata.
AB  - Tremulane sesquiterpenes ceriponols A-K, together with three known ones
      tremulenediol A, 11,12-dihydroxy-1-tremulen-5-one and conocenol B, were isolated
      from the cultures of Ceriporia lacerate, a fungal endophyte residing in the stems
      of the medicinal plant Huperzia serrata. Among these isolates, ceriponol B
      possessed an unprecedent 12-nortremulane skeleton. The structures of all isolates
      were elucidated by spectroscopic methods, including MS and NMR (1D and 2D)
      spectroscopic techniques. The cytotoxic activities of ceriponols A-K were
      evaluated against three human tumor cell lines (HeLa, HepG2, and SGC 7901).
      Ceriponols F and K exhibited moderate cytotoxicity against all the tested human
      cancer cell lines with IC50 values ranging from 32.3 +/- 0.4 to 173.2 +/- 1.5
      MUM, while ceriponol G showed slightly better cytotoxicity against a HeLa cell
      line.

PMID- 23954077
TI  - Differences in betaine lipids and fatty acids between Pseudoisochrysis paradoxa
      VLP and Diacronema vlkianum VLP isolates (Haptophyta).
AB  - Two Haptophytes were isolated from extensive aquaculture ponds at Veta La Palma
      state (Guadalquivir estuary, SW Spain). They were identified as Pseudoisochrysis
      paradoxa VLP and Diacronema vlkianum VLP based on their SSU rDNA homology to
      other Haptophytes and positioned in the Isochrysidaceae and Pavlovaceae families,
      respectively. Both Haptophytes had phosphatidilglycerol (PG) as the only
      phospholipid (PL), representing a low proportion of the total lipid content (0.8%
      in P. paradoxa VLP and 3.3% in D. vlkianum VLP). Instead, they were found to have
      different types of betaine lipids (BL) that were identified and characterized by
      HPLC/ESI-TOF-MS operating in multiple reacting monitoring (MRM) modes. P.
      paradoxa VLP had 2.2% of total lipids as diacylgyceryl-N-trimethylhomoserine
      (DGTS): it is the first Haptophyte reported to have this BL. Its total lipid
      fraction also contained 12.0% of diacylglyceryl-carboxyhydroxymethylcholine
      (DGCC) as the main BL and no diacylglyceryl-hydroxymethyl-N,N,N-trimethyl-beta
      alanine (DGTA) was detected. DGTA was only present (4.6% of total lipids) in D.
      vlkianum VLP: this was the main difference in BL content relative to P. paradoxa.
      D. vlkianum VLP also had DGTS (4.1%) and DGCC (7.6%): it is the first microalgae
      in which the simultaneous presence of these three BL has been demonstrated. The
      fatty acid profiles of P. paradoxa VLP and D. vlkianum VLP were close to those
      described for the major part of known members of the Isochrisidaceae and
      Pavlovaceae families, respectively, with the main differences due to the higher
      percentages of 18:1n9 (18.5%), 18:4n3 (12.6%) and 22:6n3 (9.3%) in the former.
      The corresponding fatty acid percentages for D. vlkianum VLP were 3.9%, 3.5% and
      3.9%, respectively. D. vlkianum VLP showed higher 16:1n7 (16.1%) and 20:5n3
      (9.4%) contents, whereas P. paradoxa VLP had significantly lower percentages of
      16:1n7 (1.7%) and 20:5n3 (0.6%). Fatty acids of BL differed between both
      haptophytes. In DGTS from P. paradoxa VLP, 90.9% of total molecular species
      consisted of the 14:0-18:1 fatty acid combination, whereas DGTS from D. vlkianum
      showed a more diverse range of fatty acids. The unsaturation index (UI) of DGTS
      was lower (55.8) than that of total lipid UI (178.3) in P. paradoxa VLP. In D.
      vlkianum VLP the UI of DGTS was higher (146.9) and similar to that for total cell
      lipids (145.9). DGTA from D. vlkianum VLP had the highest UI (321.8) of all BL
      studied and it contained maximum levels (27.7%) of 22:6n3, representing 7.1 times
      the proportion of this fatty acid in the whole lipid extract. DGCC was enriched
      in 20:5n3 by a factor of around four in both microalgae. Due to different levels
      of this fatty acid in the two microalgae their respective 20:5n3 content in DGCC
      varied from 2.2% (P. paradoxa VLP) to 41.0% (D. vlkianum VLP) and these
      concentrations were also associated with UI values of 92.2 and 271.0,
      respectively. The specific differences in BL and fatty acids described in the
      present work for two phylogenetic distant Hatophytes is a contribution to a
      better understanding on the complex relationship between lipid composition and
      taxonomy of this important Division of microalgae. Present results can also be
      useful for a more accurate identification of primary producers in food web
      studies using fatty acids and intact polar lipids as trophic markers.

PMID- 23954078
TI  - Hospital contact for mental disorders in survivors of childhood cancer and their
      siblings in Denmark: a population-based cohort study.
AB  - BACKGROUND: Survivors of childhood cancer are known to be at risk for long-term
      physical and mental effects. However, little is known about how cancers can
      affect mental health in the siblings of these patients. We aimed to assess the
      long-term risks of mental disorders in survivors of childhood cancer and their
      siblings. METHODS: Hospital contact for mental disorders was assessed in a
      population-based cohort of 7085 Danish children treated for cancer by
      contemporary protocols between 1975 and 2010 and in their 13 105 siblings by use
      of data from the Danish Psychiatric Central Research Registry. Hazard ratios
      (HRs) for first hospital contact were calculated using a Cox proportional hazards
      model. We compared these sibling and survivor cohorts with two population-based
      cohorts who were not childhood cancer survivors or siblings of survivors.
      FINDINGS: Survivors of childhood cancer were at increased risk of hospital
      contact for mental disorders, with HRs of 1.50 (95% CI 1.32-1.69) for males and
      1.26 (1.10-1.44) for females. Children younger than 10 years at diagnosis had the
      highest risk, and increased risks were seen in survivors of CNS tumours,
      haematological malignancies, and solid tumours. Survivors had higher risk of
      neurodevelopmental, emotional, and behavioural disorders than population-based
      comparisons and siblings, and male survivors had higher risk for unipolar
      depression. Overall, siblings had no excess risk for mental disorders. However,
      our data suggest that siblings who were young at the time of cancer diagnosis of
      the survivor were at increased risk for mental disorders, whereas those older
      than 15 years at diagnosis were at a lower risk than the general population.
      INTERPRETATION: Childhood cancer survivors should be followed up for mental late
      effects, especially those diagnosed in young age. Further, clinicians should also
      be aware that siblings who were young at the time of cancer diagnosis might be at
      increased risk for mental health disorders.

PMID- 23954079
TI  - The basic electrocardiogram and lethal arrhythmias in children with dilated
      cardiomyopathy.

PMID- 23954080
TI  - Effect of physiological heart rate variability on quantitative T2 measurement
      with ECG-gated Fast Spin Echo (FSE) sequence and its retrospective correction.
AB  - OBJECT: Quantitative T2 measurement is applied in cardiac Magnetic Resonance
      Imaging (MRI) for the diagnosis and follow-up of myocardial pathologies. Standard
      Electrocardiogram (ECG)-gated fast spin echo pulse sequences can be used
      clinically for T2 assessment, with multiple breath-holds. However, heart rate is
      subject to physiological variability, which causes repetition time variations and
      affects the recovery of longitudinal magnetization between TR periods. MATERIALS
      AND METHODS: The bias caused by heart rate variability on quantitative T2
      measurements is evaluated for fast spin echo pulse sequence. Its retrospective
      correction based on an effective TR is proposed. Heart rate variations during
      breath-holds are provided by the ECG recordings from healthy volunteers. T2
      measurements were performed on a phantom with known T2 values, by synchronizing
      the sequence with the recorded ECG. Cardiac T2 measurements were performed twice
      on six volunteers. The impact of T1 on T2 is also studied. RESULTS: Maximum error
      in T2 is 26% for phantoms and 18% for myocardial measurement. It is reduced by
      the proposed compensation method to 20% for phantoms and 10% for in vivo
      measurements. Only approximate knowledge of T1 is needed for T2 correction.
      CONCLUSION: Heart rate variability may cause a bias in T2 measurement with ECG
      gated FSE. It needs to be taken into account to avoid a misleading diagnosis from
      the measurements.

PMID- 23954081
TI  - Radiographic manifestations of transfusion-related acute lung injury.
AB  - OBJECTIVE: The purpose of this article is to describe the clinical symptoms and
      illustrate the radiological manifestations of transfusion-related acute lung
      injury (TRALI) as the condition develops. We mention those findings that aid the
      discrimination from transfusion-associated cardiac overload. We will also point
      some of the characteristics that increase the risk of TRALI. CONCLUSION: TRALI
      generally occurs within 1 to 2 h of the start of a blood transfusion. Though the
      radiographic features of TRALI are nonspecific, the diagnosis is established
      using clinical and radiological parameters. The diagnosis warrants a high index
      of suspicion as well as knowledge of its risk factors. There are no specific
      treatments; the best chance of survival in TRALI is with early diagnosis and
      prevention.

PMID- 23954082
TI  - Management of a distal coronary psudoaneurysm using an amplatzer vascular plug
      II.
AB  - Coronary pseudoaneurysms are rare complications of coronary perforation or
      dissection that can progress to rupture and cardiac tamponade. There is no
      optimal standard treatment, and their management is often guided by individual
      criteria including the risk of rupture, location in the coronary tree, size and
      flow in it. All of them must be taken into account when deciding the best
      treatment strategy. We report a case in which an Amplatzer Vascular Plug II (AVP
      II) was used successfully to occlude a distal coronary pseudoaneurysm that
      developed early after rescue angioplasty in a woman with a myocardial infarction
      due to spontaneous coronary dissection. 

PMID- 23954084
TI  - Hybrid positron emission tomography-magnetic resonance imaging with gallium 68
      prostate-specific membrane antigen tracer: a next step for imaging of recurrent
      prostate cancer-preliminary results.

PMID- 23954083
TI  - Definitive pathology at radical prostatectomy is commonly favorable in men
      following initial active surveillance.
AB  - BACKGROUND: Limited data are currently available regarding the outcomes of
      radical prostatectomy (RP) in men with low-risk prostate cancer who were
      initially managed by active surveillance (AS). OBJECTIVE: To evaluate the
      pathologic outcomes of patients who underwent RP following initial AS. DESIGN,
      SETTING, AND PARTICIPANTS: We analyzed the records of 67 patients who underwent
      RP following initial AS begun between 1993 and 2011. All patients underwent
      confirmatory biopsy to reassess eligibility for AS. RP was recommended for
      disease progression suggested by follow-up biopsies or imaging. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Unfavorable disease was defined as having
      at least one of the following pathologic findings: Gleason score (GS) >=4+3,
      extracapsular extension of tumor, seminal vesicle invasion, or lymph node
      involvement. A descriptive analysis was performed to assess pathologic features.
      RESULTS AND LIMITATIONS: Median time from confirmatory biopsy to RP was 1.7 yr
      (range: 0.3-7.8). Reasons for discontinuing AS to undergo RP included evidence of
      increased tumor volume or grade on follow-up biopsy, patient preference/anxiety,
      and findings on follow-up imaging in 46 patients (68.7%), 17 patients (25.3%),
      and 4 patients (6.0%), respectively. Pathologic analyses revealed organ-confined
      disease in 55 patients (82.1%), and GS was >=4+3 in 9 (13.4%). Positive nodes
      were observed in three patients (4.4%) and positive surgical margin in two
      (3.0%). Overall, 19 patients (28.4%) had unfavorable disease. Of the biopsy
      criteria for triggering RP, Gleason patterns >3 were the most frequently
      associated with unfavorable disease (43.3%). One patient (1.5%) experienced
      biochemical recurrence during postoperative follow-up (median: 3.2 yr). Our study
      may be limited by its retrospective and single-institution nature. CONCLUSIONS:
      Most patients who started initially on AS after undergoing confirmatory biopsy
      showed pathologically organ-confined disease with a low GS at RP. Such findings
      provide further evidence that, overall, AS is a safe treatment approach.

PMID- 23954085
TI  - Prostate-specific antigen-based prostate cancer screening: reduction of prostate
      cancer mortality after correction for nonattendance and contamination in the
      Rotterdam section of the European Randomized Study of Screening for Prostate
      Cancer.
AB  - BACKGROUND: Large randomized screening trials provide an estimation of the effect
      of screening at a population-based level. The effect of screening for
      individuals, however, is diluted by nonattendance and contamination in the trial
      arms. OBJECTIVE: To determine the prostate cancer (PCa) mortality reduction from
      screening after adjustment for nonattendance and contamination. DESIGN, SETTING,
      AND PARTICIPANTS: A total of 34,833 men in the core age group, 55-69 yr, were
      randomized to a screening or control arm in the Rotterdam section of the European
      Randomized Study of Screening for Prostate Cancer (ERSPC). Prostate-specific
      antigen (PSA) testing was offered to all men in the screening arm at 4-yr
      intervals. A prostate biopsy was offered to men with an elevated PSA. The primary
      end point was PCa-specific mortality. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Nonattendance was defined as nonparticipation in the screening arm.
      Contamination in the control arm was defined as receiving asymptomatic PSA
      testing or a prostate biopsy in the absence of symptoms. Relative risks (RRs)
      were calculated with an intention to screen (ITS) analysis and after correction
      for nonattendance and contamination using a method that preserves the benefits
      obtained by randomization. RESULTS AND LIMITATIONS: The ITS analysis resulted in
      an RR of 0.68 (95% confidence interval [CI], 0.53-0.89) in favor of screening at
      a median follow-up of 13 yr. Correction for both nonattendance and contamination
      resulted in an RR of 0.49 (95% CI, 0.27-0.87) in favor of screening. CONCLUSIONS:
      PCa screening as conducted in the Rotterdam section of the ERSPC can reduce the
      risk of dying from PCa up to 51% for an individual man choosing to be screened
      repeatedly compared with a man who was not screened. This benefit of screening
      should be balanced against the harms of overdiagnosis and subsequent
      overtreatment. TRIAL REGISTRATION: ISRCTN49127736.

PMID- 23954086
TI  - Somatic mutation of the androgen receptor gene is not associated with
      transitional cell carcinoma: a "negative" study by whole-exome sequencing
      analysis.

PMID- 23954087
TI  - Metastatic renal cancer: better never than late.

PMID- 23954089
TI  - Pelvic lymphadenectomy in clinically localised prostate cancer: counting lymph
      nodes or dissecting primary landing zones of the prostate?

PMID- 23954088
TI  - Analytic and clinical validation of a prostate cancer-enhanced messenger RNA
      detection assay in whole blood as a prognostic biomarker for survival.
AB  - BACKGROUND: Biomarkers based on detecting prostate cancer (PCa)-specific
      transcripts in blood are associated with inferior outcomes, but their validation
      in a clinical context is lacking. OBJECTIVE: To determine whether detecting
      enhanced transcripts for PCa in whole blood using an analytically valid assay has
      prognostic significance relative to circulating tumor cell (CTC) enumeration.
      DESIGN, SETTING, AND PARTICIPANTS: The detection of KLK3, KLK2, HOXB13, GRHL2,
      and FOXA1 in whole blood by reverse transcription polymerase chain reaction (RT
      PCR) was studied in 97 men with metastatic castration-resistant PCa (mCRPC) as a
      prognostic factor for overall survival. INTERVENTION: The 2.5 ml of blood was
      collected in PAXgene tubes for total RNA extraction and 7.5 ml for CTC
      enumeration from patients with progressive mCRPC. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: PCa-enriched genes were detected using a sensitive RT-PCR
      assay in whole blood from patients with mCRPC. Analytical validity of the assay
      was established in a clinical laboratory environment. The frequency of detecting
      transcripts was compared to CTC enumeration using CellSearch in an independent
      data set and survival associations were explored by concordance probability
      estimate (CPE). RESULTS AND LIMITATIONS: Two or more genes were detected by PCR
      in 53% of patients (51 of 97; 95% confidence interval [CI], 43-63%), and
      unfavorable CTC counts (five of more cells) were seen in 46% (45 of 97; 95% CI,
      36-56%). Importantly, transcripts were detectable in 11 of 52 patients with
      favorable CTC counts (21%; 95% CI, 8-35%). Transcript detection predicted overall
      survival in a proportional hazards model. Significantly, the predictive accuracy
      of RT-PCR detection in combination with CTC enumeration had a CPE of 0.752
      (standard error: 0.038), although this was limited by the number of patients
      evaluated. CONCLUSIONS: This validated RT-PCR assay detecting prostate-specific
      RNA in whole blood is prognostic for survival and may assess patient risk in
      tandem with CellSearch CTC enumeration. Its clinical utility is being
      prospectively explored.

PMID- 23954090
TI  - Prostate biopsies: let's move forward.

PMID- 23954092
TI  - Extracellular mitochondrial ATP, suramin, and autism?

PMID- 23954091
TI  - Treatment patterns and health care costs for patients with psoriatic arthritis on
      biologic therapy: a retrospective cohort study.
AB  - BACKGROUND: Biologic therapies have been used in patients with psoriatic
      arthritis (PsA) who have been inadequately treated with conventional disease
      modifying anti-rheumatic drugs (DMARDs). OBJECTIVE: Examine treatment patterns
      and health care costs among patients with PsAs who initiated biologic therapy
      either as monotherapy or adjunctively with traditional DMARDs. METHODS: The
      MarketScan((r)) database was used to identify adults with PsA who initiated
      therapy with a biologic (with first use identified as index date). Patients were
      required to have a 6-month pre-period with no biologic use and 1 year insurance
      eligibility pre- and post-index date. Cohorts of patients initiating biologic
      therapy either as monotherapy or adjunctively with traditional DMARDs were
      created. Medication use patterns including discontinuation, switching, and
      restarting were identified during the 1-year follow-up period. Cox proportional
      hazards models were conducted to compare time to discontinuation of index
      biologic, and logistic models were used to compare the rate of discontinuation
      and biologic switching between the 2 cohorts. All-cause and PsA-related costs
      were compared between the 2 cohorts using propensity score-adjusted bootstrapping
      methods. All comparisons were made after adjusting for age, sex, Charlson
      comorbidity index, and PsA-related total cost over 1-year pre-index date.
      RESULTS: Among the 3164 PsA patients identified, 67.7% initiated biologics as
      monotherapy and 32.3% initiated biologics adjunctively with traditional DMARDs.
      The number of patients on pain medications, topical medications, and traditional
      DMARDs was significantly lower post index date compared to pre-index date (P <
      0.01), while use of antihypertensives, antidiabetics, and statins increased after
      patients initiated biologic therapy. In 1-year post-period, approximately half of
      the patients (50.9%) who initiated a biologic continued their index biologic with
      an average time to discontinuation of 279.8 days for all patients. Rates of
      discontinuation, switching, and restart were 33.1%, 9.9%, and 6.1%, respectively,
      for all patients. Rates of switching and restart were similar between the 2
      cohorts, but a significantly lower rate of discontinuation was observed in the
      biologic plus traditional DMARDs cohort than the biologic monotherapy cohort.
      Pharmacy expenditures were higher for the biologic + DMARD cohort than the
      biologic-monotherapy cohort ($14,486 vs $14,062; P = 0.0348). No statistically
      significant differences for either all-cause or PsA-specific costs were observed
      across the treatment cohorts. CONCLUSIONS: Traditional DMARDs used in combination
      with biologic therapy appear to reduce rates of biologic therapy discontinuation.

PMID- 23954093
TI  - Analysis of inpatient use of fresh frozen plasma and other therapies and
      associated outcomes in patients with major bleeds from vitamin K antagonism.
AB  - OBJECTIVE: We conducted an observational study of outcomes and costs associated
      with fresh frozen plasma (FFP) use in patients receiving warfarin with
      intracerebral, gastrointestinal, or musculoskeletal bleeding. METHODS: Patients
      who had at least 1 International Classification of Diseases, Ninth Revision code
      indicative of anticoagulation history, received >= 1 unit FFP, and had patient
      costs >$0 were identified from a database of >600 US hospitals. The main outcome
      was transfusion of additional blood products (eg, cryoprecipitate, red blood
      cells, or platelets) or vitamin K. Further outcomes included administration of
      other bleeding-related therapies (eg, recombinant activated factor VII, albumin,
      or crystalloids), incidence of fluid overload, days in the intensive care unit,
      discharge status, and total hospital costs. RESULTS: The most frequently
      administered products were vitamin K and red blood cells, given to 55.6% to 61.0%
      and 19.2% to 29.3% of patients, respectively. The number of FFP units transfused
      correlated highly with fluid overload (r > 0.91) and was associated with
      inpatient mortality, nonhome discharge, and intensive care unit admittance. For
      both inpatient mortality and nonhome discharge, the odds ratio was significant
      when >= 4 units FFP were transfused (P < 0.05). A dose of >2 units FFP was
      associated with an increased probability of an intensive care unit stay (P <
      0.05). Total costs were greater among patients receiving >2 units FFP compared
      with patients who received 1 unit FFP (P < 0.001), with a substantial increase in
      costs incurred when >= 4 units FFP were transfused. CONCLUSIONS: In patients with
      warfarin-related bleeding, inpatient mortality, nonhome discharge, intensive care
      unit admission, and hospital costs were associated with the number of units of
      FFP transfused.

PMID- 23954094
TI  - Management of extensive talar osteolysis with AgilityTM total ankle replacement
      systems using geometric metal-reinforced polymethylmethacrylate cement
      augmentation.
AB  - The AgilityTM Total Ankle Replacement System, almost exclusively without
      polymethylmethacrylate cement fixation, was the most commonly used implant in the
      United States from 1998 to 2007. Much attention has been given to the
      intraoperative complications and incision healing-related problems. However, it
      is the intermediate- and long-term complications, specifically, aseptic
      osteolysis, talar component loosening, subsidence, and progressive malalignment,
      that require careful consideration, because the revision options are limited. We
      describe a technique for management of extensive talar aseptic osteolysis for
      revision of AgilityTM total ankle replacement systems with use of geometric metal
      reinforced polymethylmethacrylate cement augmentation. This technique preserves
      the subtalar joint, provides immediate component stability and restoration of
      component alignment and height, and is a cost-effective alternative to other
      available options and still allows for additional revision should late failure
      occur. 

PMID- 23954095
TI  - Tarsal tunnel syndrome secondary to schwannoma of the posterior tibial nerve.
AB  - Schwannoma is a benign tumor that arises from the peripheral nerve sheath. It
      presents as a discrete, often tender, and palpable nodule associated with
      neurogenic pain or paresthesia when compressed or traumatized. The growth rate is
      usually slow, and these lesions seldom exceed 2 cm in diameter. We report the
      case of a large schwannoma arising from the posterior tibial nerve located in the
      posterior medial ankle. The core needle biopsy findings were suggestive of a
      schwannoma, with spindle cells strongly and uniformly immunostaining for S-100
      protein. The mass was marginally excised. The surgical specimen consisted of a
      grossly encapsulated white-yellow mass with irregular contours, measuring 3.7 *
      3.5 * 2.7 cm. The cut surface showed areas of pin-point hemorrhage. The patient
      did not encounter any motor deficits; however, early results showed some
      subjective numbness. Few reports have been published of schwannomas arising from
      the tibial nerve. Marginal excision appears to be the recommended therapy for
      this tumor, without any evidence of recurrence at 9 months of follow-up. 

PMID- 23954096
TI  - Associations between physical activity and the built environment in patients with
      schizophrenia: a multi-centre study.
AB  - OBJECTIVE: This study investigated the variance in walking, moderate and vigorous
      physical activity (PA), explained by neighbourhood design and other environmental
      variables above and beyond the variance accounted for by demographical variables.
      METHOD: A total of 138 patients (46?) with schizophrenia (mean age = 41.2 +/-
      12.5 years) from 13 different centres in Belgium were included in this 4-month
      cross-sectional study. The built environment was rated using the Instruments for
      Assessing Levels of Physical Activity and Fitness (ALPHA) environmental
      questionnaire, which was validated first. PA levels were assessed with the
      International Physical Activity Questionnaire. RESULTS: Validity coefficients for
      the ALPHA ranged between 0.44 and 0.86 and test-retest reliability intraclass
      correlation coefficients ranged between 0.64 and 0.84. Regression analyses showed
      that environmental variables were related to all types of PA. The variance
      explained by the models including demographic and environmental variables ranged
      from 20% for vigorous PA up to 68% for walking. Minutes of walking (r=0.63,
      P<.001) and of moderate-intensity PA (r = 0.43, P<.001) were related to emotional
      satisfaction with the environment. Moderate-intensity PA was also related to the
      presence of PA supplies at home (r=0.49, P<.001). CONCLUSION: Neighbourhood
      design and other environmental variables show significant associations with
      multiple types of PA in patients with schizophrenia.

PMID- 23954098
TI  - Drug-DNA intercalation: from discovery to the molecular mechanism.
AB  - The ability of small molecules to perturb the natural structure and dynamics of
      nucleic acids is intriguing and has potential applications in cancer
      therapeutics. Intercalation is a special binding mode where the planar aromatic
      moiety of a small molecule is inserted between a pair of base pairs, causing
      structural changes in the DNA and leading to its functional arrest. Enormous
      progress has been made to understand the nature of the intercalation process
      since its idealistic conception five decades ago. However, the biological
      functions were detected even earlier. In this review, we focus mainly on the
      acridine and anthracycline types of drugs and provide a brief overview of the
      development in the field through various experimental methods that led to our
      present understanding of the subject. Subsequently, we discuss the molecular
      mechanism of the intercalation process, free-energy landscapes, and kinetics that
      was revealed recently through detailed and rigorous computational studies. 

PMID- 23954097
TI  - Calcium plus vitamin D supplementation and joint symptoms in postmenopausal women
      in the women's health initiative randomized trial.
AB  - BACKGROUND: Low vitamin D intake and levels have been associated with increased
      joint symptoms in some observational studies but the findings are mixed and
      evidence from randomized trials sparse. OBJECTIVE: To evaluate the influence of
      supplemental calcium and vitamin D on joint symptoms in the Women's Health
      Initiative randomized, placebo-controlled, clinical trial. DESIGN: In post hoc
      analyses, the results of the Women's Health Initiative randomized clinical trial
      in which 36,282 postmenopausal women were randomized to receive calcium carbonate
      (1,000 mg as elemental calcium) with vitamin D-3 (400 IU) daily or placebo were
      examined in the 6% subgroup of 1,911 participants, oversampled for minorities,
      who had serial joint symptom assessment. Qualitative information on joint pain
      and joint swelling was collected by questionnaire before entry and 2 years after
      randomization. Logistic regression models were used to compare the occurrence and
      severity of joint symptoms across randomization groups. RESULTS: At baseline,
      total calcium and vitamin D intakes from diet and supplements were similar in the
      two randomization groups. In addition, both joint pain (reported by 73%) and
      joint swelling (reported by 34%) were commonly reported and comparable in the
      supplement and placebo groups. Two years after randomization, no statistically
      significant differences between supplement and placebo groups were seen for joint
      pain frequency (74.6% compared with 75.1% [P=0.79] for supplement and placebo
      groups, respectively) or joint swelling frequency (34.6% compared with 32.4%
      [P=0.29], respectively) or in severity scores for either outcome. Subgroup
      analyses suggested study participants also using nonprotocol calcium supplements
      at study entry may have less joint pain with supplement group randomization
      (interaction P=0.02). CONCLUSIONS: Joint symptoms are relatively common in
      postmenopausal women. However, daily supplementation with 1,000 mg calcium
      carbonate and 400 IU vitamin D-3 in a randomized, placebo-controlled clinical
      trial setting did not reduce the self-reported frequency or severity of joint
      symptoms.

PMID- 23954099
TI  - Ligand docking simulations by generalized-ensemble algorithms.
AB  - In protein chemistry and structural biology, conventional simulations in physical
      statistical mechanical ensembles, such as the canonical ensemble with fixed
      temperature and isobaric-isothermal ensemble with fixed temperature and pressure,
      face a great difficulty. This is because there exist a huge number of local
      minimum-energy states in the system and the conventional simulations tend to get
      trapped in these states, giving wrong results. Generalized-ensemble algorithms
      are based on artificial unphysical ensembles and overcome the above difficulty by
      performing random walks in potential energy, volume, and other physical
      quantities or their corresponding conjugate parameters such as temperature and
      pressure. The advantage of generalized-ensemble simulations lies in the fact that
      they not only avoid getting trapped in states of energy local minima but also
      allow the calculations of physical quantities as functions of temperature or
      other parameters from a single simulation run. In this chapter, we review the
      generalized-ensemble algorithms. Some of their specific examples such as replica
      exchange molecular dynamics and replica-exchange umbrella sampling are described
      in detail. Examples of their applications to drug design are presented. 

PMID- 23954100
TI  - Conformational dynamics of single protein molecules studied by direct mechanical
      manipulation.
AB  - Advances in single-molecule manipulation techniques have recently enabled
      researchers to study a growing array of biological processes in unprecedented
      detail. Individual molecules can now be manipulated with subnanometer precision
      along a simple and well-defined reaction coordinate, the molecular end-to-end
      distance, and their conformational changes can be monitored in real time with
      ever-improving time resolution. The behavior of biomolecules under tension
      continues to unravel at an accelerated pace and often in combination with
      computational studies that reveal the atomistic details of the process under
      investigation. In this chapter, we explain the basic principles of force
      spectroscopy techniques, with a focus on optical tweezers, and describe some of
      the theoretical models used to analyze and interpret single-molecule manipulation
      data. We then highlight some recent and exciting results that have emerged from
      this research field on protein folding and protein-ligand interactions. 

PMID- 23954101
TI  - Generation of ligand specificity and modes of oligomerization in beta-prism I
      fold lectins.
AB  - beta-Prism I fold lectins constitute one of the five widely occurring structural
      classes of plant lectins. Each single domain subunit is made up of three Greek
      key motifs arranged in a threefold symmetric fashion. The threefold symmetry is
      not reflected in the sequence except in the case of the lectin from banana, a
      monocot, which carries two sugar-binding sites instead of the one in other
      lectins of known three-dimensional structure, all from dicots. This is believed
      to be a consequence of the different evolutionary paths followed by the lectin in
      monocots and dicots. The galactose-specific lectins among them have two chains
      produced by posttranslational proteolysis and contain three aromatic residues at
      the binding site. The extended binding sites of galactose- and mannose-specific
      lectins have been thoroughly characterized. Ligand binding at the sites involves
      both conformational selection and induced fit. Molecular plasticity of some of
      the lectins in the family has been characterized. The plasticity appears to be
      such as to promote variability in quaternary association which could be dimeric,
      tetrameric, or octameric. Structural and evolutionary reasons for the variability
      have been explored, and the relation of oligomerization to ligand binding and
      conformational selection investigated. 

PMID- 23954102
TI  - Conformational changes of enzymes and DNA in molecular dynamics: influenced by
      pH, temperature, and ligand.
AB  - Protein conformation, which has been a research hotspot for human diseases, is an
      important factor of protein properties. Recently, a series of approaches have
      been utilized to investigate the conformational changes under different
      conditions. Some of them have gained promising achievements, but it is still
      deficient in the detail researches at the atomic level. In this chapter, a series
      of computational examples of protein conformational changes under different pH
      environment, temperature, and ligand binding are described. We further show some
      useful methods, such as constant pH molecular dynamics simulations, molecular
      docking, and molecular mechanics Poisson-Boltzmann surface area/generalized Born
      surface area calculations. In comparison with the experimental results, the
      methods mentioned above are reasonable to detect and predict the interaction
      between residue and residue, residue and DNA, and residue and ligand.
      Additionally, some crucial interactions that cause protein conformational changes
      are discovered and discussed in this chapter. In summary, our work can give
      penetrating information to understand the pH-, temperature-, and ligand-induced
      conformational change mechanisms. 

PMID- 23954103
TI  - Protein functional dynamics in multiple timescales as studied by NMR
      spectroscopy.
AB  - Protein functional dynamics are defined as the atomic thermal fluctuations or the
      segmental motions that are essential for the function of the biomolecule. NMR is
      a very versatile technique that allows obtaining quantitative information from
      these processes at atomic resolution. This review is focused on the use of 15N
      spin relaxation methods to study functional dynamics although the connections
      with other NMR methods and biophysical techniques will be briefly mentioned. In
      the first part of the chapter, methodological aspects will be considered, while a
      set of selected cases will be described in more detail in the second part.

PMID- 23954104
TI  - Protein-DNA electrostatics: toward a new paradigm for protein sliding.
AB  - Gene expression and regulation rely on an apparently finely tuned set of
      reactions between some proteins and DNA. Such DNA-binding proteins have to find
      specific sequences on very long DNA molecules and they mostly do so in the
      absence of any active process. It has been rapidly recognized that, to achieve
      this task, these proteins should be efficient at both searching (i.e., sampling
      fast relevant parts of DNA) and finding (i.e., recognizing the specific site). A
      two-mode search and variants of it have been suggested since the 1970s to explain
      either a fast search or an efficient recognition. Combining these two properties
      at a phenomenological level is, however, more difficult as they appear to have
      antagonist roles. To overcome this difficulty, one may simply need to drop the
      dichotomic view inherent to the two-mode search and look more thoroughly at the
      set of interactions between DNA-binding proteins and a given DNA segment either
      specific or nonspecific. This chapter demonstrates that, in doing so in a very
      generic way, one may indeed find a potential reconciliation between a fast search
      and an efficient recognition. Although a lot remains to be done, this could be
      the time for a change of paradigm. 

PMID- 23954105
TI  - Structural and dynamical aspects of HIV-1 protease and its role in drug
      resistance.
AB  - Acquired immunodeficiency syndrome (AIDS) caused by the retrovirus human
      immunodeficiency virus (HIV) has become a major epidemic afflicting mankind. The
      Joint United Nations Program on HIV/AIDS (UNAIDS) projection shows the existence
      of millions of AIDS patients at the end of 2012. All the Food and Drug
      Administration (FDA)-approved drugs are getting ineffective due to resistance
      offered by the mutation-prone HIV. Hence, there is an urgent need for developing
      new drugs with greater potential. HIV life cycle is controlled by the activities
      of its essential proteins like glycoproteins (gp41 and gp120), HIV reverse
      transcriptase (HIV-RT), HIV integrase (HIV-IN), and HIV-1 protease (HIV-pr). This
      chapter focuses on the protein HIV-pr, which is important for the cleavage of Gag
      and Gag-Pol polyproteins to form mature, structural, and functional virions. The
      conformation and dynamics of the protein HIV-pr play a pivotal role in ligand
      binding and the catalytic process, which is affected by the rapid point mutations
      and various physiological parameters. The effect of the mutations and the varied
      simulation protocols on conformational dynamics and drug resistance of HIV-pr is
      discussed. 

PMID- 23954106
TI  - Introduction to dynamics of proteins and nucleic acids.

PMID- 23954107
TI  - Speech disturbs face scanning in 6-month-old infants who develop autism spectrum
      disorder.
AB  - BACKGROUND: From birth, infants show a preference for the faces, gaze, and voices
      of others. In individuals with autism spectrum disorders (ASDs) these biases seem
      to be disturbed. The source of these disturbances is not well-understood, but
      recent efforts have shown that the spontaneous deployment of attention to social
      targets might be atypical as early as 6 months of age. The nature of this
      atypical behavior and the conditions under which it arises are currently unknown.
      METHODS: We used eye-tracking to examine the gaze patterns of 6-month-old infants
      (n = 99) at high risk (n = 57) and low risk (n = 42) for developing ASD as they
      viewed faces that were: 1) still; 2) moving and expressing positive affect; or 3)
      speaking. Clinical outcomes were determined through a comprehensive assessment at
      the age of 3 years. The scanning patterns of infants later diagnosed with ASD
      were compared with infants without an ASD outcome. RESULTS: Infants who later
      developed ASD spent less time looking at the presented scenes in general than
      other infants. When these infants looked at faces, their looking toward the inner
      features of faces decreased compared with the other groups only when the
      presented face was speaking. CONCLUSIONS: Our study suggests that infants later
      diagnosed with ASD have difficulties regulating attention to complex social
      scenes. It also suggests that the presence of speech might uniquely disturb the
      attention of infants who later develop ASD at a critical developmental point when
      other infants are acquiring language and learning about their social world.

PMID- 23954109
TI  - Cortical thickness, surface area, and gyrification abnormalities in children
      exposed to maltreatment: neural markers of vulnerability?
AB  - BACKGROUND: Childhood maltreatment has been shown to significantly elevate the
      risk of psychiatric disorder. Previous neuroimaging studies of children exposed
      to maltreatment have reported atypical neural structure in several regions,
      including the prefrontal cortex and temporal lobes. These studies have
      exclusively investigated volumetric differences rather than focusing on
      genetically and developmentally distinct indices of brain structure. METHODS:
      Here we used surface-based methods to examine cortical thickness, surface area,
      and local gyrification in a community sample of children with documented
      experiences of abuse (n = 22) and a group of carefully matched nonmaltreated
      peers (n = 21). RESULTS: Reduced cortical thickness in the maltreated compared
      with the nonmaltreated group was observed in an extended cluster that
      incorporated the anterior cingulate, superior frontal gyrus, and orbitofrontal
      cortex. In addition, reduced cortical surface area was observed within the
      parcellated regions of the left middle temporal area and lingual gyrus. Local
      gyrification deficits within the maltreated group were located within two
      clusters, the lingual gyrus and the insula extending into pars opercularis.
      CONCLUSIONS: This is the first time structural abnormalities in the anterior
      cingulate and lingual gyrus have been detected in children exposed to
      maltreatment. Surface-based methods seem to capture subtle, previously
      undetected, morphological abnormalities associated with maltreatment. We suggest
      that these approaches detect developmental precursors of brain volume differences
      seen in adults with histories of abuse. Because the reported regions are
      implicated in several clinical disorders, they might constitute biological
      markers of vulnerability, linking exposure to early adversity and psychiatric
      risk.

PMID- 23954108
TI  - Population-based analysis of Alzheimer's disease risk alleles implicates genetic
      interactions.
AB  - BACKGROUND: Reported odds ratios and population attributable fractions (PAF) for
      late-onset Alzheimer's disease (LOAD) risk loci (BIN1, ABCA7, CR1, MS4A4E, CD2AP,
      PICALM, MS4A6A, CD33, and CLU) come from clinically ascertained samples. Little
      is known about the combined PAF for these LOAD risk alleles and the utility of
      these combined markers for case-control prediction. Here we evaluate these loci
      in a large population-based sample to estimate PAF and explore the effects of
      additive and nonadditive interactions on LOAD status prediction performance.
      METHODS: 2419 samples from the Cache County Memory Study were genotyped for APOE
      and nine LOAD risk loci from AlzGene.org. We used logistic regression and
      receiver operator characteristic analysis to assess the LOAD status prediction
      performance of these loci using additive and nonadditive models and compared odds
      ratios and PAFs between AlzGene.org and Cache County. RESULTS: Odds ratios were
      comparable between Cache County and AlzGene.org when identical single nucleotide
      polymorphisms were genotyped. PAFs from AlzGene.org ranged from 2.25% to 37%;
      those from Cache County ranged from .05% to 20%. Including non-APOE alleles
      significantly improved LOAD status prediction performance (area under the curve =
      .80) over APOE alone (area under the curve = .78) when not constrained to an
      additive relationship (p < .03). We identified potential allelic interactions (p
      values uncorrected): CD33-MS4A4E (synergy factor = 5.31; p < .003) and CLU-MS4A4E
      (synergy factor = 3.81; p < .016). CONCLUSIONS: Although nonadditive interactions
      between loci significantly improve diagnostic ability, the improvement does not
      reach the desired sensitivity or specificity for clinical use. Nevertheless,
      these results suggest that understanding gene-gene interactions may be important
      in resolving Alzheimer's disease etiology.

PMID- 23954110
TI  - Flexion strength of the toes in the normal foot. An evaluation using magnetic
      resonance imaging.
AB  - Flexion of the toes may be active from muscle contraction or passive from the
      reversed windlass function of the plantar aponeurosis. The aim of this study was
      to estimate the flexion moments the muscles of the foot and long digital flexors
      may be capable of generating and compare these calculations with published data.
      Magnetic resonance images were used to measure the maximal cross-sectional area
      of the foot muscles and long digital flexors, along with the radius of curvature
      of the metatarsal heads. Using known physiological data the maximal flexion
      moments the muscles may be able to generate at the metatarsophalangeal (MTP)
      joints were calculated. The methodology overestimates muscle strength and flexion
      moments at the metatarsophalangeal joints. The calculated maximal flexion moment
      at the 1st MTP joint is 4.27-6.84 Nm, for the 2nd, 3rd and 4th MTP joints 3.06
      4.91 Nm, and the 5th MTP joint 0.47-0.75 Nm. The flexion moments the muscles may
      generate at the MTP joints do not account for the flexion forces seen in normal
      walking. Given that maximal strength is not used in normal walking, we conclude
      that the reversed windlass mechanism of the plantar aponeurosis must be important
      in normal function of the toes.

PMID- 23954111
TI  - IGF-I levels and visceral fat accumulation in colonic neoplasia.
AB  - BACKGROUND: IGF-I, visceral obesity, IGF binding protein-3 and insulin are
      reported to be potential risk factors for colorectal carcinogenesis. Many studies
      report a relation between obesity, insulin resistance and the risk of colon
      cancer. This study investigates the association between IGF-I levels, insulin
      resistance and visceral fat accumulation in patients with colon cancer and
      adenoma. METHODS: In this cross sectional study, 48 sequential patients were
      diagnosed with either colorectal adenoma or carcinoma were enrolled. The control
      subjects were 30 sequential subjects. Serum IGF-I, HOMA insulin resistance index
      and visceral fat were measured in patients with colorectal adenoma and carcinoma.
      RESULTS: Serum IGF-I levels were significantly higher in patients with colorectal
      adenoma and carcinoma compared with controls. Visceral fat accumulation was lower
      in colorectal carcinoma group compared with colorectal adenoma group, but no
      statistically significant difference was observed among them and controls. No
      statistically significant difference was observed in HOMA insulin resistance
      index, fasting insulin and fasting glucose concentrations among the three groups.
      No correlation was found between insulin resistance and serum IGF-I levels and
      visceral fat accumulation. Logistic regression analysis showed that plasma IGF-I
      concentration was significantly associated with colorectal adenoma and carcinoma.
      Body mass index and waist circumference were associated with colorectal,
      carcinoma but were not associated with adenoma. CONCLUSION: In our study we found
      that, IGF-I levels are associated with colorectal adenomas and carcinomas,
      independent of insulin resistance and visceral fat accumulation; supporting the
      hypothesis that an increase in IGF-I levels may be a factor involved in the
      development of colon cancer.

PMID- 23954112
TI  - Naturotherapy as a potential source of mould infections in patients with
      haematological malignancies.

PMID- 23954113
TI  - Asymptomatic carriage of toxigenic Clostridium difficile by hospitalized
      patients.
AB  - Asymptomatic carriage of Clostridium difficile is common in hospitals, but the
      risk for transmission by carriers is unclear. In this point prevalence culture
      survey of asymptomatic hospitalized patients, 18 of 149 (12%) were carriers of
      toxigenic C. difficile. By comparison with C. difficile infection (CDI) patients,
      the prevalence of skin and/or environmental contamination was significantly lower
      in asymptomatic carriers (3/18, 17% versus 5/6, 83%; P = 0.007), but carriers
      outnumbered CDI patients in the hospital by a factor of 3 to 1. These data
      suggest that asymptomatic carriers have the potential to contribute to C.
      difficile transmission in hospitals. 

PMID- 23954114
TI  - [Pathology practice is not a bed of rose...].

PMID- 23954115
TI  - [Placental pathology of uteroplacental vascular deficiency].
AB  - The indications of the pathological examination of the placenta are mainly
      represented by uteroplacental vascular deficiency. The clinical context is often
      evocative, but it can sometimes be solely an intra-uterine growth retardation or
      an unexplained in utero fetal death. So, the pathological lesions of this
      uteroplacental vascular deficiency must be well-known to be correctly
      interpreted, for none of these lesions is truly specific. The pathological
      diagnosis is based on a group of macroscopic and microscopic arguments. Various
      physiopathological mechanisms, often imperfectly known, can be at the origin of
      an uteroplacental vascular insufficiency, but in the current position, the
      pathological examination does not allow etiopathogenic orientation. The
      development of the trophoblastic biopsies gives us access to a new material
      which, in parallel with the cytogenetic analysis, often allows us, in front of an
      unexplained intra-uterine growth retardation, to direct the diagnosis towards
      uteroplacental vascular insufficiency. The histological analysis of the chorionic
      villous sampling taken precociously during pathological pregnancies is thus a
      major diagnostic contribution. But especially, this analysis gives access to new
      information which, in the near future, will enable us to better define the
      pathological evolution of the lesions of hypoxic chorionic villous and to
      contribute to a better knowledge of this pathology which, under many aspects,
      still conceals many mysteries. 

PMID- 23954116
TI  - [Benign mimickers of the prostate cancer. Diagnostic challenges].
AB  - The diagnosis of prostate cancer (PCa), especially limited adenocarcinoma on
      needle biopsy, is often challenging. Before making diagnosis of PCa, it is
      prudent for the pathologist to consider different benign patterns that may lead
      to a false positive interpretation. Histoanatomic structures such as seminal
      vesicles, Cowper's glands and paraganglia along with hyperplasia, atrophy with
      its different patterns and adenosis may generate difficulties in differential
      diagnosis. Furthermore, inflammatory processes and post-treatment changes may
      cause problems. The above entities can in some instances simulate low-grade and
      less commonly high grade PCa. Knowledge of these patterns and application of
      appropriate immunohistochemistry will lead the pathologist to a correct
      diagnosis.

PMID- 23954117
TI  - [Digestive tumors and pseudotumors that rarely get discussed. Introduction].

PMID- 23954118
TI  - [Digestive tumors and pseudotumors that rarely get discussed. Case 1: colonic
      diverticulosis].

PMID- 23954119
TI  - [Digestive tumors and pseudotumors that rarely get discussed. Case 2: calcifying
      fibrous tumor].

PMID- 23954120
TI  - [Digestive tumors and pseudotumors that rarely get discussed. Case 3: colonic
      mucosal/submucosal elongated polyp].

PMID- 23954121
TI  - [Digestive tumors and pseudotumors that rarely get discussed. Case 4: malignant
      mesothelioma of the peritoneum].

PMID- 23954123
TI  - [Cutaneous lymphoid hyperplasia (pseudolymphoma) on the red dye of a tattoo].
AB  - Cutaneous lymphoid hyperplasia (pseudolymphoma) on tattoo is rare. The diagnosis
      is histological. We report a case of cutaneous lymphoid hyperplasia within the
      red ink of a tattoo found on a 35-year-old man presenting multiple infiltrated
      nodules confined to the red areas of his tattoo, which he had done 2 months ago.
      The pathological examination showed a diffuse lympho-histiocytic dermo-hypodermal
      infiltrate, associated with a lichenoid reaction. Immunohistochemistry displayed
      T-cell infiltration (CD3+, CD5+, CD8+). The treatment is difficult, knowing that
      the spontaneous regression seems possible, and the progression into a lymphoma is
      exceptional in the case of a chronic evolution over a number of years.

PMID- 23954122
TI  - [Large cell calcifying Sertoli cell tumour: A case report].
AB  - A 19-year-old male Caucasian, without prior medical history, noticed a painless
      right testicular mass. Physical examination revealed neither gynecomastia nor
      abnormal skin pigmentation. Serum alpha-fetoprotein, beta-HCG and testosterone
      levels were normal. Sonography depicted an intratesticular diffusely hyperechoic
      lesion with acoustic shadowing. The patient underwent right orchiectomy.
      Histology revealed a benign large cell calcifying Sertoli cell tumour. This
      tumour is rare and may be associated with genetic abnormalities. 

PMID- 23954124
TI  - [Hemophagocytic lymphohistiocytosis associated with a lymphohistiocytic pattern
      anaplastic large cell lymphoma: a case report].
AB  - We report the case of a 16-year-old girl with an anaplastic large cell lymphoma
      of lymphohistiocytic pattern revealed by a hemophagocytic syndrome.
      Histologically, the lymphomatous population was concealed by clusters of
      histiocytes. Immunohistochemical study allowed the diagnosis. The combination of
      these two entities is rarely described and may be a source of delay in diagnosis
      of a life-threatening condition. 

PMID- 23954125
TI  - [A giant abdominal cyst].

PMID- 23954126
TI  - [Atypical presentation of an odontogenic tumor: a case report].

PMID- 23954127
TI  - [A rare vaginal tumor].

PMID- 23954128
TI  - [A paratesticular lesion].

PMID- 23954129
TI  - Structural and biochemical features of acidic alpha-amylase of Bacillus
      acidicola.
AB  - The investigation is aimed at understanding structure-function aspect of alpha
      amylase of an acidophilic bacterium Bacillus acidicola (BAamy), which is Ca(2+)
      independent and active at acidic pH of native starch, and thus, suits better in
      starch saccharification process. The CD spectroscopic data analysis revealed that
      the enzyme has 30% alpha-helices, 14.2% beta-sheets, and 55.8% random coils at 60
      degrees C and pH 4.0. Using Bacillus stearothermophilus alpha-amylase (BStA) as
      the template, 3-D structure of rBAamy has been proposed. A complete loss in alpha
      amylase activity was recorded when the amino acid residues (D231, E261 and D328)
      were substituted that confirmed their role in catalysis. The CD studies indicated
      a decrease in the alpha-helices content below and beyond the optimum pH and
      temperature that suggests a critical role of alpha-helix in maintaining the
      structural conformation of the enzyme. Fluorescence-quenching by N
      bromosuccinimide (NBS) suggested the role of tryptophan in maintaining structural
      integrity of alpha-amylase and that by acrylamide indicated interaction by simple
      collision process.

PMID- 23954130
TI  - Group 3 innate lymphoid cells inhibit T-cell-mediated intestinal inflammation
      through aryl hydrocarbon receptor signaling and regulation of microflora.
AB  - Aryl hydrocarbon receptor (Ahr) is crucial for the maintenance and function of
      group 3 innate lymphoid cells (ILCs), which are important in gut immunity.
      Because Ahr promotes T helper 17 (Th17) cell differentiation in vitro, it is
      reasonable to expect that Ahr would enhance Th17 cells in vivo. Instead, we show
      that Ahr deficiency caused increased intestinal Th17 cells, raising the
      possibility that group 3 ILCs could negatively regulate Th17 cells. Reduced
      innate interleukin-22 (IL-22) in Ahr-deficient mice allowed expansion of
      commensal segmented filamentous bacteria (SFB), known to promote Th17 cells.
      Compared to Rorc(+/+)Ahr(-/-) mice, Rorc(gfp/+)Ahr(-/-) mice had further reduced
      group 3 ILCs and were prone to spontaneous colitis with increased SFB and Th17
      cells. Innate expression of Ahr played a protective role in T-cell-mediated
      experimental colitis by suppressing pathogenic Th17 cells. Our data reveal an
      intricate balance between ILCs and Th17 cells regulated by Ahr and commensal
      flora. 

PMID- 23954131
TI  - Canonical Wnt signaling negatively modulates regulatory T cell function.
AB  - Foxp3 is crucial for both the development and function of regulatory T (Treg)
      cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional
      output remain poorly defined. Here, we demonstrate that T cell factor 1 (TCF1)
      and Foxp3 associates in Treg cells and that active Wnt signaling disrupts Foxp3
      transcriptional activity. A global chromatin immunoprecipitation sequencing
      comparison in Treg cells revealed considerable overlap between Foxp3 and Wnt
      target genes. The activation of Wnt signaling reduced Treg-mediated suppression
      both in vitro and in vivo, whereas disruption of Wnt signaling in Treg cells
      enhanced their suppressive capacity. The activation of effector T cells increased
      Wnt3a production, and Wnt3a levels were found to be greatly increased in
      mononuclear cells isolated from synovial fluid versus peripheral blood of
      arthritis patients. We propose a model in which Wnt produced under inflammatory
      conditions represses Treg cell function, allowing a productive immune response,
      but, if uncontrolled, could lead to the development of autoimmunity. 

PMID- 23954132
TI  - Interleukin-33-dependent innate lymphoid cells mediate hepatic fibrosis.
AB  - Liver fibrosis is a consequence of chronic liver diseases and thus a major cause
      of mortality and morbidity. Clinical evidence and animal studies suggest that
      local tissue homeostasis is disturbed due to immunological responses to chronic
      hepatocellular stress. Poorly defined stress-associated inflammatory networks are
      thought to mediate gradual accumulation of extracellular-matrix components,
      ultimately leading to fibrosis and liver failure. Here we have reported that
      hepatic expression of interleukin-33 (IL-33) was both required and sufficient for
      severe hepatic fibrosis in vivo. We have demonstrated that IL-33's profibrotic
      effects related to activation and expansion of liver resident innate lymphoid
      cells (ILC2). We identified ILC2-derived IL-13, acting through type-II IL-4
      receptor-dependent signaling via the transcription factor STAT6 and hepatic
      stellate-cell activation, as a critical downstream cytokine of IL-33-dependent
      pathologic tissue remodeling and fibrosis. Our data reveal key immunological
      networks implicated in hepatic fibrosis and support the concept of modulation of
      IL-33 bioactivity for therapeutic purposes. 

PMID- 23954134
TI  - Gastrostomy insertion in head and neck cancer patients: a 3 year review of
      insertion method and complication rates.
AB  - Patients with head and neck cancer who have resection, radiotherapy,
      chemoradiotherapy, or a combination of these require nutritional support to be
      implemented before treatment, and this may involve insertion of a prophylactic
      gastrostomy feeding tube. The aim of this study was to compare the use and
      complication rates of percutaneous endoscopic gastrostomy (PEG) and
      radiologically inserted gastrostomy (RIG) in these patients at a tertiary
      referral centre. We retrospectively reviewed gastrostomy data forms completed by
      nutritional support nursing staff over a recent 34-month period, which included
      information on method of insertion, 30-day postoperative serious and minor
      complications, and mortality. A total of 110 patients had prophylactic insertion
      of a gastrostomy (21 PEG, 89 RIG) over the study period. In the first 12 months
      13 (31%) PEG feeding tubes were placed but in the last 12 months none were
      inserted using an endoscopic approach. Serious complications occurred with 2
      (10%) PEG and 12 (13%) RIG; the most common cause was accidental removal of the
      tube (n=13, 12%). Minor complications of peristomal infection, leakage, or
      blockage of the tube occurred in 6 (5%) gastrostomies. No patients died during
      the study period. In recent years, and in the absence of recommended guidelines,
      there has been an increase in the elective insertion of RIG in patients with head
      and neck cancer. Serious complications for both methods of insertion in this
      study are comparable with similar reports. However, with RIG there is a high rate
      of tubes becoming dislodged with the potential for serious consequences. The most
      appropriate method to insert a gastrostomy tube in patients with head and neck
      cancer remains unclear. 

PMID- 23954135
TI  - Six-year retrospective study of reconstructive options for defects of the skull
      base after resection of tumour.
AB  - The successful management of tumours that involve the skull base depends on
      resection and reconstruction of the defect. The challenge is to create a
      protective vascularised seal between the intracranial contents and the adjacent
      paranasal sinuses, nasopharynx, and oral cavity. Failure to create a protective
      barrier for the intracranial contents can result in cerebrospinal fistulas,
      potentially fatal infections, and radiotherapy being delayed. Local or regional
      flaps may be adequate for small defects, but larger ones require microsurgical
      free tissue transfer. As a part of the skull base surgical team, we present our
      experience in the reconstruction of defects after resection of tumours. A total
      of 41 patients had operations over a 6-year period from January 2004 to January
      2010, and 26 free tissue transfer flaps and 20 local or regional flaps (46 flaps)
      were used for reconstruction. Ninety-two percent of the free flaps were
      successful. We also report details on disease, complications, and survival at 3,
      6, and 12 months. Survival depended not only on the type of disease, coexisting
      conditions, and adequate resection of tumour, but equally on the reconstruction
      of the defect. 

PMID- 23954133
TI  - Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation.
AB  - Nlrp3 inflammasome activation occurs in response to numerous agonists but the
      specific mechanism by which this takes place remains unclear. All previously
      evaluated activators of the Nlrp3 inflammasome induce the generation of
      mitochondrial reactive oxygen species (ROS), suggesting a model in which ROS is a
      required upstream mediator of Nlrp3 inflammasome activation. Here we have
      identified the oxazolidinone antibiotic linezolid as a Nlrp3 agonist that
      activates the Nlrp3 inflammasome independently of ROS. The pathways for ROS
      dependent and ROS-independent Nlrp3 activation converged upon mitochondrial
      dysfunction and specifically the mitochondrial lipid cardiolipin. Cardiolipin
      bound to Nlrp3 directly and interference with cardiolipin synthesis specifically
      inhibited Nlrp3 inflammasome activation. Together these data suggest that
      mitochondria play a critical role in the activation of the Nlrp3 inflammasome
      through the direct binding of Nlrp3 to cardiolipin. 

PMID- 23954136
TI  - PCR slippage across the ML-2 microsatellite of the Cryptosporidium MIC1 locus
      enables development of a PCR assay capable of distinguishing the zoonotic
      Cryptosporidium parvum from other human infectious Cryptosporidium species.
AB  - Cryptosporidium are ubiquitous and significant enteropathogens of all classes of
      vertebrates and a major cause of human morbidity and mortality worldwide. Of the
      24 recognized species, the zoonotic Cryptosporidium parvum and the host-specific
      Cryptosporidium hominis cause the majority of cases of human cryptosporidiosis.
      Here, we report on structural and transcriptional variability between C. parvum
      and C. hominis at the MIC1 locus, which encodes a microneme localized
      thrombospondin-like domain containing protein previously demonstrated to be
      critical for host cell infection by C. parvum. We demonstrate, using reverse
      transcription quantitative PCR with the aid of genomic data from the EuPathDB
      site, that the transcribed product in C. hominis is both truncated and
      significantly down-regulated in the sporozoite. We hypothesize that CpMIC1 may be
      a genetic factor involved in facilitating the wider host range of C. parvum in
      comparison with the specific host range of C. hominis. Furthermore, we show that
      the presence of a microsatellite (ML-2) within the C. parvum MIC-1 locus enables
      the development of a PCR marker that can rapidly distinguish the zoonotic C.
      parvum from C. hominis and other significant human infectious Cryptosporidium
      species due to reproducible PCR slippage across the ML-2 microsatellite.
      Additionally, we demonstrate that this locus is tightly linked to the GP60 locus,
      a locus commonly used in the genetic characterization of C. parvum and C. hominis
      isolates. This marker should provide a robust and additional tool to aid in the
      rapid identification of C. parvum from other Cryptosporidium species.

PMID- 23954138
TI  - Phosphaturic mesenchymal tumor, nonphosphaturic variant, causing fatal pulmonary
      metastasis.
AB  - Phosphaturic mesenchymal tumors of the mixed connective tissue type (PMT-MCTs)
      are rare neoplasms, most of which are benign and cause tumor-induced osteomalacia
      because of overproduction of a phosphaturic hormone, fibroblast growth factor 23
      (FGF23). This entity may have been unrecognized or misdiagnosed as other
      mesenchymal tumors, such as giant cell tumor, hemangiopericytoma, and
      osteosarcoma. Ten percent of these tumors, without phosphaturia, were diagnosed
      only by their histologic features. We report here the first case of malignant PMT
      MCT, nonphosphaturic variant, resulting in fatal multiple lung metastases.
      Chondromyxoid matrix with "grungy" calcification, multinucleated giant cell
      proliferation, and expression of FGF23 mRNA (reverse transcription-polymerase
      chain reaction) and fibroblast growth factor 23 protein (immunohistochemistry)
      were seen in the primary and recurrent tumors of the right foot. The lung
      metastases showed flocculent calcification and FGF23 protein expression as well
      as giant cell proliferation. This unique case highlights the need for careful
      histologic assessment of PMT-MCTs, especially the nonphosphaturic variant, and
      the need for recognition of its rare malignant behavior. 

PMID- 23954137
TI  - Feasibility and toxicity of concurrent chemoradiation for elderly patients with
      head and neck cancer.
AB  - OBJECTIVES: Although concurrent chemoradiation is increasingly used for patients
      with locally advanced head and neck cancer, many elderly patients receive
      radiation alone due to toxicity concerns. We evaluate acute and late toxicity
      among patients age >= 65 who received concurrent chemoradiation for head and neck
      cancer. DESIGN: Retrospective review. SETTING: Tertiary care center.
      PARTICIPANTS: Between 6/2003 and 8/2011, 40 consecutive patients age >= 65
      underwent combined chemoradiation for head and neck cancer. Ten patients were
      treated in the postoperative setting and 30 underwent definitive chemoradiation.
      Twenty-eight patients received concurrent platinum-based chemotherapy and 12
      received concurrent weekly paclitaxel. Treatment plans were designed to provide a
      dose of 66-72 Gy at 2-2.12 Gy/fraction to >95% of the gross tumor volume in the
      definitive setting or for positive margins and 60-66 Gy at 2 Gy/fraction post
      operatively. Median follow-up was 23.2 months (range: 0-94.4 months). MAIN
      OUTCOMES MEASURES: Acute skin and mucosal toxicity, unplanned treatment
      interruptions, and chronic treatment related toxicity including gastrostomy tube
      dependence as graded by the CTCAE v3.0. RESULTS: Eight patients (20%) required a
      radiation treatment break of >= 3 days. Thirteen (33%) required unplanned
      hospitalization during or immediately following treatment. No grade 4+ skin or
      mucosal toxicity was noted. Five patients remained PEG tube dependent at >1 year.
      One patient developed non-healing mandibular osteoradionecrosis >3 years
      following chemoradiation. The 2-year Kaplan-Meier estimate of overall survival
      was 55%. CONCLUSION: Higher-than-expected rates of in-patient hospitalization
      with significant acute toxicity were noted in this cohort with a correspondingly
      high rate of radiation treatment breaks. Late toxicity rates were similar to
      those observed in historical controls with younger patients. Careful patient
      selection criteria should be employed for elderly patients considering concurrent
      chemoradiation for head and neck cancer.

PMID- 23954139
TI  - Reliable identification of transition zone prostatic adenocarcinoma in
      preoperative needle core biopsy.
AB  - Prostatic adenocarcinomas arising within the transition zone (Tz) are distinct
      from peripheral zone (Pz) tumors as regards biological aggression and mechanism
      of extraprostatic extension. Reliable biopsy identification of Tz tumors would
      allow targeted surgical approaches more likely to preserve erectile function
      without compromising surgical margins. Previous studies have demonstrated the
      presence of eosinophilic cytoplasmic granules (prostate secretory granules, or
      PSGs) after glutaraldehye fixation, with apparent depletion in neoplasia. We
      investigated PSG content, columnar cells, pale cytoplasm, and luminal secretions
      of both Pz and Tz tumors in 44 radical prostatectomies (RPs) and 135 biopsies
      fixed with gluteraldehyde-based fixative. Retention of PSG is characteristic of
      Tz carcinoma and infrequently seen in Pz tumors, and a combination of PSG greater
      than 30% with either columnar cells, pale cells, or secretions in biopsies is a
      reliable marker for Tz origin. When these criteria were prospectively applied to
      3929 cases with follow-up RP, 510 Tz tumors were correctly identified on biopsy
      (sensitivity, 21.4%; specificity, 97.4%). Biopsy-identified Tz tumors had higher
      volumes (mean, 3.48 versus 1.81 cm(3); P < .001) and higher rates of margin
      positivity (22.5% versus 17.5%; P = .008) than did Tz tumors not identified
      preoperatively. Mean Tz tumor length in biopsies was 2.0 mm, with no correlation
      between tumor volume at RP and tumor length on biopsy. Tz tumors are reliably
      identified on biopsy, based on a combination of PSG retention with either
      columnar cells, pale cells, or secretion. Biopsy-identified Tz tumors may not be
      suitable for active surveillance because of an associated high probability of
      large tumor volume and increased risk of positive margins at RP. 

PMID- 23954140
TI  - Clinicopathologic significance of immunostaining of alpha-thalassemia/mental
      retardation syndrome X-linked protein and death domain-associated protein in
      neuroendocrine tumors.
AB  - alpha-Thalassemia/mental retardation syndrome X-linked protein (ATRX) and death
      domain-associated protein (DAXX) genes are tumor suppressors whose mutations have
      been identified in sporadic pancreatic neuroendocrine tumors as well as in
      patients with MEN1. However, it is unknown whether ATRX and DAXX alterations are
      specific for pancreatic neuroendocrine tumor. In addition, the association of
      ATRX/DAXX protein loss with tumor cell proliferation has not been examined. We,
      therefore, immunostained ATRX and DAXX in 10 gastric, 15 duodenal, 20 rectal, 70
      pancreatic, and 22 pulmonary neuroendocrine tumors with 15 nonneoplastic
      pancreases and 27 pancreatic adenocarcinomas to elucidate the site-specific roles
      of ATRX/DAXX abnormalities. At least 1 loss of ATRX and DAXX immunoreactivity was
      detected in all neuroendocrine tumor cases but not in any of nonneoplastic
      pancreatic tissues or pancreatic adenocarcinomas. The loss of DAXX protein was
      correlated with the Ki-67 index (ATRX, P = .904; DAXX, P = .044). The status of
      DAXX immunoreactivity correlated positively with World Health Organization
      histologic grade (P = .026). These results suggest that the status of ATRX or
      DAXX protein loss in neuroendocrine tumor differed among the organs in which
      these tumors arose, and these proteins may play site-specific roles in the
      development of these tumors. 

PMID- 23954141
TI  - [Phenotypic heterogeneity and phenotype-genotype correlations in
      dystrophinopathies: Contribution of genetic and clinical databases].
AB  - The objective of this work was to study the natural history of dystrophinopathies
      and the genotype-phenotype correlations made possible by the development of the
      clinical part of the French DMD database. The collection of 70,000 clinical data
      for 600 patients with an average longitudinal follow-up of 12years enabled
      clarification of the natural history of Duchenne and Becker muscular dystrophies
      and clinical presentations in symptomatic females. We were able to specify the
      phenotypic heterogeneity of motor, orthopedic and respiratory involvements
      (severe, standard and intermediary form), of the cardiac disorder (severe,
      standard or absent cardiomyopathy, absence of correlation between motor and
      cardiac involvements), and of brain function (mental deficiency in the patients
      with Becker muscular dystrophy, psychopathological disorders in
      dystrophinopathies). Phenotypic variability did not correlate with a specific
      mutational spectrum. We propose a model of phenotypic analysis based on the
      presence or not of muscular and cardiac involvements (described by age at onset
      and rate of progression) and brain involvement (described by the type and the
      severity of the cognitive impairment and of the psychological disorders). The
      methodology developed for the DMD gene can be generalized and used for other
      databases dedicated to genetic diseases. Application of this model of phenotypic
      analysis for each patient and further development of the database should
      contribute substantially to clinical research providing useful tools for future
      clinical trials. 

PMID- 23954142
TI  - A balance of interleukin-12 and -23 in cancer.
AB  - Interleukin (IL)-12 and IL-23 share the IL-12p40 molecule. IL-12 promotes T
      helper (Th)1 immunity and IL-23 promotes Th17 immunity, and it has recently
      become apparent that the balance between IL-12 and IL-23 is important in
      carcinogenesis. A series of studies demonstrated that, where tumor initiation,
      growth, and metastasis are concerned, IL-12 may act independently of interferon
      (IFN)-gamma, and IL-23 independently of IL-17A. This review explores the activity
      of IL-23 in carcinogenesis. In the context of the tumor-inhibitory effects of IL
      12, and tumor-promoting effects of IL-23, we discuss the use of anti-IL-12p/23
      monoclonal antibodies (mAbs) in autoimmune inflammatory disorders and the
      alternative specific neutralization of IL-23. 

PMID- 23954144
TI  - Options for metastatic colorectal cancer beyond the second line of treatment.
AB  - Colorectal cancer is the third most common cancer, with recent advances in the
      management of unresectable metastatic lesions. The aim of this review is to
      discuss the remaining options for heavily pretreated patients with unresectable
      metastatic colorectal cancer. Beyond second-line treatment, two epidermal growth
      factor receptor (EGFR) inhibitors, cetuximab and panitumumab, have a demonstrated
      clinical interest in patients with KRAS wild-type tumours. However, few data
      exist in patients pretreated with an anti-EFGR and who are being rechallenged
      with anti-EGFR drugs. Reintroduction of chemotherapy should be considered. In
      September 2012, regorafenib, a multi-kinase inhibitor was approved by the US
      Federal Drug Administration for patients refractory to other standard treatments.
      In the case of metastases limited to the liver, transarterial chemoembolization,
      hepatic artery infusion and radioembolization could also be discussed in selected
      patients. With the multiplication of therapeutic options in first-line, second
      line treatment, and beyond, the concept of subsequent lines of chemotherapy
      should be replaced by a multiline strategy, dependent on the patient and on
      tumour biology. A better understanding of the tumour biology and predictive
      factors for the response to these therapies is needed, and further strategic
      trials are urgently warranted. 

PMID- 23954143
TI  - B7 family checkpoint regulators in immune regulation and disease.
AB  - Fine-tuning the immune response and maintaining tolerance to self-antigens
      involves a complex network of co-stimulatory and co-inhibitory molecules. The
      recent FDA approval of ipilimumab, a monoclonal antibody blocking cytotoxic T
      lymphocyte antigen (CTLA)-4, demonstrates the impact of checkpoint regulators in
      disease. This is reinforced by ongoing clinical trials targeting not only CTLA-4,
      but also the programmed death (PD)-1 and B7-H4 pathways in various disease
      states. Recently, two new B7 family inhibitory ligands, V-domain Ig suppressor of
      T cell activation (VISTA) and B7-H6 were identified. Here, we review recent
      understanding of B7 family members and their concerted regulation of the immune
      response to either self or foreign pathogens. We also discuss clinical
      developments in targeting these pathways in different disease settings, and
      introduce VISTA as a putative therapeutic target. 

PMID- 23954145
TI  - Familiarity preference in schizophrenia is associated with ambivalent attitudes
      towards others.
AB  - OBJECTIVE: Preferences or attitudes towards others are often shaped through
      implicit memory processes, and they serve a critical function in our social
      lives. Preferences driven by implicit familiarity (mere exposure effect) are
      particularly important when making judgments about others and forming attitudes
      of liking and social interaction. In schizophrenia, little is known about the
      effect of familiarity preference on judgments and attitudes toward others.
      METHODS: Subjects included 79 patients with a diagnosis of schizophrenia or
      schizoaffective disorder and 61 non-patient control subjects. Familiarity
      preference and trait judgments about others were assessed using a computer task
      in which neutral faces were rated on positive and negative character traits.
      "Attractiveness" was rated twice at the beginning and at the end, to measure
      familiarity preference. Clinical ratings were also obtained. RESULTS: Patients
      and controls both demonstrated a positive familiarity preference effect. However,
      the groups differed on the predictive value of familiarity preference for trait
      judgments. In both groups, the presence of a familiarity preference effect
      predicted greater positive trait judgments. In patients only, the presence of a
      familiarity preference effect also predicted, although the correlation was less
      significant, greater negative trait judgments. CONCLUSION: The findings are
      consistent with a preserved familiarity preference effect in individuals with
      schizophrenia and that the effect is primarily associated with changes in
      positive attitudes. However, in individuals with schizophrenia this effect is
      also linked with inferences about negative traits, resulting in ambivalence
      towards others. This finding may contribute to the impaired social functioning of
      people with schizophrenia.

PMID- 23954146
TI  - Mindfulness interventions for psychosis: a meta-analysis.
AB  - BACKGROUND: An increasing number of mindfulness interventions are being used with
      individuals with psychosis or schizophrenia, but no known meta-analysis has
      investigated their effectiveness. OBJECTIVE: To evaluate the efficacy of
      mindfulness interventions for psychosis or schizophrenia, we conducted an effect
      size analysis of initial studies. DATA SOURCES: A systematic review of studies
      published in journals or in dissertations in PubMED, PsycINFO or MedLine from the
      first available date until July 25, 2013. REVIEW METHODS: A total of 13 studies
      (n=468) were included. RESULTS: Effect-size estimates suggested that mindfulness
      interventions are moderately effective in pre-post analyses (n=12; Hedge's
      g=.52). When compared with a control group, we found a smaller effect size (n=7;
      Hedge's g=.41). The obtained results were maintained at follow-up when data were
      available (n=6; Hedge's g=.62 for pre-post analyses; results only approached
      significance for controlled analyses, n=3; Hedge's g=.55, p=.08). Results
      suggested higher effects on negative symptoms compared with positive ones. When
      combined together, mindfulness, acceptance, and compassion strongly moderated the
      clinical effect size. However, heterogeneity was significant among the trials,
      probably due to the diversity of interventions included and outcomes assessed.
      CONCLUSION: Mindfulness interventions are moderately effective in treating
      negative symptoms and can be useful adjunct to pharmacotherapy; however, more
      research is warranted to identify the most effective elements of mindfulness
      interventions.

PMID- 23954147
TI  - Reduced delta power and synchrony and increased gamma power during the P3 time
      window in schizophrenia.
AB  - BACKGROUND: Event-related potential studies in schizophrenia have demonstrated
      amplitude reduction of the P3 in oddball tasks. The P3 has been linked to
      attention and memory brain functions. METHODS: In 24 schizophrenia patients and
      28 control subjects, wavelet transform was used to reveal event-related
      modulations of the EEG signal during target trials in delta, theta, alpha, beta,
      and gamma frequency bands. RESULTS: Patients showed reductions in P3 amplitude
      accompanied by reduced low frequency delta-theta and increased beta-gamma band
      EEG activity. CONCLUSIONS: These results indicate abnormalities in the
      synchronization and/or efficiency of neural processes involved in memory and
      attention networks in schizophrenia.

PMID- 23954148
TI  - The effect of childhood maltreatment and cannabis use on adult psychotic symptoms
      is modified by the COMT Val158Met polymorphism.
AB  - BACKGROUND: Cannabis use and childhood maltreatment are independent risk factors
      for the development of psychotic symptoms. These factors have been found to
      interact in some but not all studies. One of the reasons may be that childhood
      maltreatment and cannabis primarily induce psychotic symptoms in genetically
      susceptible individuals. In this context, an extensively studied psychosis
      vulnerability gene is catechol-methyl-transferase (COMT). Therefore, we aimed to
      examine whether the COMT Val(158)Met polymorphism (rs4680) moderates the
      interaction between childhood maltreatment and cannabis use on psychotic symptoms
      in the general population. METHOD: The discovery sample consisted of 918
      individuals from a cross-sectional study. For replication we used an independent
      sample of 339 individuals from the general population. RESULTS: A significant
      three-way interaction was found between childhood maltreatment, cannabis use, and
      the COMT genotype (rs4680) in the discovery sample (P=0.006). Val-homozygous
      individuals displayed increased psychotic experiences after exposure to both
      cannabis use and childhood maltreatment compared to Met-heterozygous and Met
      homozygous individuals. Supportive evidence was found in the replication sample
      with similar effect and direction even though the results did not reach
      statistical significance (P=0.25). CONCLUSIONS: These findings suggest that a
      functional polymorphism in the COMT gene may moderate the interaction between
      childhood maltreatment and cannabis use on psychotic experiences in the general
      population. In conclusion, the COMT Val(158)Met polymorphism may constitute a
      genetic risk factor for psychotic symptoms in the context of combined exposure to
      childhood maltreatment and cannabis use.

PMID- 23954149
TI  - Viruses PLAY DEAD to TAMe interferon responses.
AB  - TAM receptors promote apoptotic cell uptake and function as inflammation
      suppressors. Many viruses mimic apoptotic cells, thus exploiting TAM receptors
      for attachment and entry. In this issue of Cell Host & Microbe, Bhattacharyya et
      al. show that TAM binding by enveloped viruses also induces receptor signaling to
      suppress cellular interferon responses. 

PMID- 23954150
TI  - Bacterial persistence: finding the "sweet spot".
AB  - Studies described by Eisele et al. (2013) and Xavier et al. (2013) in this issue
      of Cell Host & Microbe show that the bacterial pathogens Salmonella and Brucella
      exploit the increased levels of glucose present in alternatively activated
      macrophages to sustain chronic infections in experimentally infected mice. 

PMID- 23954151
TI  - First impressions in a glowing host-microbe partnership.
AB  - Despite the clear significance of beneficial animal-microbe associations,
      mechanisms underlying their initiation and establishment are rarely understood.
      In this issue of Cell Host & Microbe, Kremer et al. (2013) reveal that first
      contact within the squid-vibrio symbiosis triggers profound molecular and
      chemical changes that are crucial for bacterial colonization. 

PMID- 23954152
TI  - Merkel cell polyomavirus small T antigen controls viral replication and
      oncoprotein expression by targeting the cellular ubiquitin ligase SCFFbw7.
AB  - Merkel cell polyomavirus (MCV) causes an aggressive human skin cancer, Merkel
      cell carcinoma, through expression of small T (sT) and large T (LT) viral
      oncoproteins. MCV sT is also required for efficient MCV DNA replication by the
      multifunctional MCV LT helicase protein. We find that LT is targeted for
      proteasomal degradation by the cellular SCF(Fbw7) E3 ligase, which can be
      inhibited by sT through its LT-stabilization domain (LSD). Consequently, sT also
      stabilizes cellular SCF(Fbw7) targets, including the cell-cycle regulators c-Myc
      and cyclin E. Mutating the sT LSD decreases LT protein levels and eliminates
      synergism in MCV DNA replication as well as sT-induced cell transformation.
      SCF(Fbw7) knockdown mimics sT-mediated stabilization of LT, but this knockdown is
      insufficient to fully reconstitute the transforming activity of a mutant LSD sT
      protein. Thus, MCV has evolved a regulatory system involving SCF(Fbw7) that
      controls viral replication but also contributes to host cell transformation. 

PMID- 23954153
TI  - Enveloped viruses disable innate immune responses in dendritic cells by direct
      activation of TAM receptors.
AB  - Upon activation by the ligands Gas6 and Protein S, Tyro3/Axl/Mer (TAM) receptor
      tyrosine kinases promote phagocytic clearance of apoptotic cells and downregulate
      immune responses initiated by Toll-like receptors and type I interferons (IFNs).
      Many enveloped viruses display the phospholipid phosphatidylserine on their
      membranes, through which they bind Gas6 and Protein S and engage TAM receptors.
      We find that ligand-coated viruses activate TAM receptors on dendritic cells
      (DCs), dampen type I IFN signaling, and thereby evade host immunity and promote
      infection. Upon virus challenge, TAM-deficient DCs display type I IFN responses
      that are elevated in comparison to wild-type cells. As a consequence, TAM
      deficient DCs are relatively resistant to infection by flaviviruses and
      pseudotyped retroviruses, but infection can be restored with neutralizing type I
      IFN antibodies. Correspondingly, a TAM kinase inhibitor antagonizes the infection
      of wild-type DCs. Thus, TAM receptors are engaged by viruses in order to
      attenuate type I IFN signaling and represent potential therapeutic targets. 

PMID- 23954154
TI  - The second messenger phosphatidylinositol-5-phosphate facilitates antiviral
      innate immune signaling.
AB  - Innate immune receptors, notably Toll-like receptors (TLRs) and RIG-I-like
      receptors (RLRs), sense viral infection and activate transcription factors,
      including interferon regulatory factor-3 (IRF3), to induce type I interferon
      (IFN). We demonstrate that the lipid phosphatidylinositol-5-phosphate (PtdIns5P)
      is increased upon viral infection and facilitates type I IFN production by
      binding to IRF3 and its upstream kinase TBK1 and promoting TBK1-mediated IRF3
      phosphorylation and activation. Additionally, we determine that PtdIns5P is
      produced through the kinase PIKfyve, which phosphorylates PtdIns to generate
      PtdIns5P. Accordingly, PIKfyve knockdown or pharamoclogical inhibition decreases
      PtdIns5P levels and type I IFN production after TLR or RLR stimulation, and
      results in increased viral replication. A synthetic PtdIns5P, C8-PtdIns5P,
      promotes IRF3 phosphorylation and cytokine production in dendritic cells and acts
      as an adjuvant to boost immune responses in immunized mice. Thus, PtdIns5P
      produced during viral infection is a second messenger that targets the TBK1-IRF3
      axis to elicit antiviral immunity. 

PMID- 23954155
TI  - PPARgamma-mediated increase in glucose availability sustains chronic Brucella
      abortus infection in alternatively activated macrophages.
AB  - Eradication of persistent intracellular bacterial pathogens with antibiotic
      therapy is often slow or incomplete. However, strategies to augment antibiotics
      are hampered by our poor understanding of the nutritional environment that
      sustains chronic infection. Here we show that the intracellular pathogen Brucella
      abortus survives and replicates preferentially in alternatively activated
      macrophages (AAMs), which are more abundant during chronic infection. A metabolic
      shift induced by peroxisome proliferator-activated receptor gamma (PPARgamma),
      which increases intracellular glucose availability, is identified as a causal
      mechanism promoting enhanced bacterial survival in AAMs. Glucose uptake was
      crucial for increased replication of B. abortus in AAMs, and for chronic
      infection, as inactivation of the bacterial glucose transporter gluP reduced both
      intracellular survival in AAMs and persistence in mice. Thus, a shift in
      intracellular nutrient availability induced by PPARgamma promotes chronic
      persistence of B. abortus within AAMs, and targeting this pathway may aid in
      eradicating chronic infection. 

PMID- 23954156
TI  - Salmonella require the fatty acid regulator PPARdelta for the establishment of a
      metabolic environment essential for long-term persistence.
AB  - Host-adapted Salmonella strains are responsible for a number of disease
      manifestations in mammals, including an asymptomatic chronic infection in which
      bacteria survive within macrophages located in systemic sites. However, the host
      cell physiology and metabolic requirements supporting bacterial persistence are
      poorly understood. In a mouse model of long-term infection, we found that S.
      typhimurium preferentially associates with anti-inflammatory/M2 macrophages at
      later stages of infection. Further, PPARdelta, a eukaryotic transcription factor
      involved in sustaining fatty acid metabolism, is upregulated in Salmonella
      infected macrophages. PPARdelta deficiency dramatically inhibits Salmonella
      replication, which is linked to the metabolic state of macrophages and the level
      of intracellular glucose available to bacteria. Pharmacological activation of
      PPARdelta increases glucose availability and enhances bacterial replication in
      macrophages and mice, while Salmonella fail to persist in Ppardelta null mice.
      These data suggest that M2 macrophages represent a unique niche for long-term
      intracellular bacterial survival and link the PPARdelta-regulated metabolic state
      of the host cell to persistent bacterial infection. 

PMID- 23954157
TI  - Initial symbiont contact orchestrates host-organ-wide transcriptional changes
      that prime tissue colonization.
AB  - Upon transit to colonization sites, bacteria often experience critical priming
      that prepares them for subsequent, specific interactions with the host; however,
      the underlying mechanisms are poorly described. During initiation of the
      symbiosis between the bacterium Vibrio fischeri and its squid host, which can be
      observed directly and in real time, approximately five V. fischeri cells
      aggregate along the mucociliary membranes of a superficial epithelium prior to
      entering host tissues. Here, we show that these few early host-associated
      symbionts specifically induce robust changes in host gene expression that are
      critical to subsequent colonization steps. This exquisitely sensitive response to
      the host's specific symbiotic partner includes the upregulation of a host
      endochitinase, whose activity hydrolyzes polymeric chitin in the mucus into
      chitobiose, thereby priming the symbiont and also producing a chemoattractant
      gradient that promotes V. fischeri migration into host tissues. Thus, the host
      responds transcriptionally upon initial symbiont contact, which facilitates
      subsequent colonization. 

PMID- 23954158
TI  - Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E
      cadherin/beta-catenin signaling via its FadA adhesin.
AB  - Fusobacterium nucleatum (Fn) has been associated with colorectal cancer (CRC),
      but causality and underlying mechanisms remain to be established. We demonstrate
      that Fn adheres to, invades, and induces oncogenic and inflammatory responses to
      stimulate growth of CRC cells through its unique FadA adhesin. FadA binds to E
      cadherin, activates beta-catenin signaling, and differentially regulates the
      inflammatory and oncogenic responses. The FadA-binding site on E-cadherin is
      mapped to an 11-amino-acid region. A synthetic peptide derived from this region
      of E-cadherin abolishes FadA-induced CRC cell growth and oncogenic and
      inflammatory responses. The fadA gene levels in the colon tissue from patients
      with adenomas and adenocarcinomas are >10-100 times higher compared to normal
      individuals. The increased FadA expression in CRC correlates with increased
      expression of oncogenic and inflammatory genes. This study unveils a mechanism by
      which Fn can drive CRC and identifies FadA as a potential diagnostic and
      therapeutic target for CRC. 

PMID- 23954159
TI  - Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the
      tumor-immune microenvironment.
AB  - Increasing evidence links the gut microbiota with colorectal cancer. Metagenomic
      analyses indicate that symbiotic Fusobacterium spp. are associated with human
      colorectal carcinoma, but whether this is an indirect or causal link remains
      unclear. We find that Fusobacterium spp. are enriched in human colonic adenomas
      relative to surrounding tissues and in stool samples from colorectal adenoma and
      carcinoma patients compared to healthy subjects. Additionally, in the Apc(Min/+)
      mouse model of intestinal tumorigenesis, Fusobacterium nucleatum increases tumor
      multiplicity and selectively recruits tumor-infiltrating myeloid cells, which can
      promote tumor progression. Tumors from Apc(Min/+) mice exposed to F. nucleatum
      exhibit a proinflammatory expression signature that is shared with human
      fusobacteria-positive colorectal carcinomas. However, unlike other bacteria
      linked to colorectal carcinoma, F. nucleatum does not exacerbate colitis,
      enteritis, or inflammation-associated intestinal carcinogenesis. Collectively,
      these data suggest that, through recruitment of tumor-infiltrating immune cells,
      fusobacteria generate a proinflammatory microenvironment that is conducive for
      colorectal neoplasia progression. 

PMID- 23954160
TI  - A deficiency in the autophagy gene Atg16L1 enhances resistance to enteric
      bacterial infection.
AB  - Polymorphisms in the essential autophagy gene Atg16L1 have been linked with
      susceptibility to Crohn's disease, a major type of inflammatory bowel disease
      (IBD). Although the inability to control intestinal bacteria is thought to
      underlie IBD, the role of Atg16L1 during extracellular intestinal bacterial
      infections has not been sufficiently examined and compared to the function of
      other IBD susceptibility genes, such as Nod2, which encodes a cytosolic bacterial
      sensor. We find that Atg16L1 mutant mice are resistant to intestinal disease
      induced by the model bacterial pathogen Citrobacter rodentium. An Atg16L1
      deficiency alters the intestinal environment to mediate an enhanced immune
      response that is dependent on monocytic cells, but this hyperimmune phenotype and
      its protective effects are lost in Atg16L1/Nod2 double-mutant mice. These results
      reveal an immunosuppressive function of Atg16L1 and suggest that gene variants
      affecting the autophagy pathway may have been evolutionarily maintained to
      protect against certain life-threatening infections. 

PMID- 23954161
TI  - Results of Baha(r) implantation using a small horizontal incision.
AB  - PURPOSE: Techniques for Baha(r) implantation continue to evolve. The Weber
      technique, utilizing a 1.5 cm horizontal incision for Baha(r) implantation is
      evaluated. METHODS: Retrospective review of patients undergoing Baha(r)
      implantation by a single surgeon over three years. RESULTS: 33 Baha(r)s implanted
      in 30 patients. Fourteen used an Inverted J (IJ) incision with an anteriorly
      based skin-flap, 13 with the Weber technique (W). Five were not included as other
      techniques were used. Demographics and weeks to activation (14.58 vs 13.4, p =
      0.12) were similar. There were no differences in the number of patients with
      minor complications (5 vs 2, p = 0.22) or number of minor complications (20 vs 4,
      p = 0.09). One patient in the IJ Group required operative revision for
      overgrowth. There were no infections in the IJ Group, and one requiring oral
      antibiotics in the W Group. Follow-up was longer in the IJ Group (41 vs 13 weeks,
      p = 0.016), no complications occurred after 14 weeks post-op. Mean operative
      times were similar (43 vs 39 min, p = 0.59). There were no cases of skin flap
      necrosis in either group. CONCLUSION: A small incision for Baha(r) implantation
      proved as effective, without increased complications as a skin-flap based
      technique.

PMID- 23954162
TI  - DrGaP: a powerful tool for identifying driver genes and pathways in cancer
      sequencing studies.
AB  - Cancers are caused by the accumulation of genomic alterations. Driver mutations
      are required for the cancer phenotype, whereas passenger mutations are irrelevant
      to tumor development and accumulate through DNA replication. A major challenge
      facing the field of cancer genome sequencing is to identify cancer-associated
      genes with mutations that drive the cancer phenotype. Here, we describe a
      powerful and flexible statistical framework for identifying driver genes and
      driver signaling pathways in cancer genome-sequencing studies. Biological
      knowledge of the mutational process in tumors is fully integrated into our
      statistical models and includes such variables as the length of protein-coding
      regions, transcript isoforms, variation in mutation types, differences in
      background mutation rates, the redundancy of genetic code, and multiple mutations
      in one gene. This framework provides several significant features that are not
      addressed or naively obtained by previous methods. In particular, on the
      observation of low prevalence of somatic mutations in individual tumors, we
      propose a heuristic strategy to estimate the mixture proportion of chi-square
      distribution of likelihood ratio test (LRT) statistics. This provides
      significantly increased statistical power compared to regular LRT. Through a
      combination of simulation and analysis of TCGA cancer sequencing study data, we
      demonstrate high accuracy and sensitivity in our methods. Our statistical methods
      and several auxiliary bioinformatics tools have been incorporated into a
      computational tool, DrGaP. The newly developed tool is immediately applicable to
      cancer genome-sequencing studies and will lead to a more complete identification
      of altered driver genes and driver signaling pathways in cancer. 

PMID- 23954163
TI  - Additive genetic variation in schizophrenia risk is shared by populations of
      African and European descent.
AB  - To investigate the extent to which the proportion of schizophrenia's additive
      genetic variation tagged by SNPs is shared by populations of European and African
      descent, we analyzed the largest combined African descent (AD [n = 2,142]) and
      European descent (ED [n = 4,990]) schizophrenia case-control genome-wide
      association study (GWAS) data set available, the Molecular Genetics of
      Schizophrenia (MGS) data set. We show how a method that uses genomic similarities
      at measured SNPs to estimate the additive genetic correlation (SNP correlation
      [SNP-rg]) between traits can be extended to estimate SNP-rg for the same trait
      between ethnicities. We estimated SNP-rg for schizophrenia between the MGS ED and
      MGS AD samples to be 0.66 (SE = 0.23), which is significantly different from 0
      (p(SNP-rg = 0) = 0.0003), but not 1 (p(SNP-rg = 1) = 0.26). We re-estimated SNP
      rg between an independent ED data set (n = 6,665) and the MGS AD sample to be
      0.61 (SE = 0.21, p(SNP-rg = 0) = 0.0003, p(SNP-rg = 1) = 0.16). These results
      suggest that many schizophrenia risk alleles are shared across ethnic groups and
      predate African-European divergence. 

PMID- 23954164
TI  - Whole-genome sequencing uncovers the genetic basis of chronic mountain sickness
      in Andean highlanders.
AB  - The hypoxic conditions at high altitudes present a challenge for survival,
      causing pressure for adaptation. Interestingly, many high-altitude denizens
      (particularly in the Andes) are maladapted, with a condition known as chronic
      mountain sickness (CMS) or Monge disease. To decode the genetic basis of this
      disease, we sequenced and compared the whole genomes of 20 Andean subjects (10
      with CMS and 10 without). We discovered 11 regions genome-wide with significant
      differences in haplotype frequencies consistent with selective sweeps. In these
      regions, two genes (an erythropoiesis regulator, SENP1, and an oncogene, ANP32D)
      had a higher transcriptional response to hypoxia in individuals with CMS relative
      to those without. We further found that downregulating the orthologs of these
      genes in flies dramatically enhanced survival rates under hypoxia, demonstrating
      that suppression of SENP1 and ANP32D plays an essential role in hypoxia
      tolerance. Our study provides an unbiased framework to identify and validate the
      genetic basis of adaptation to high altitudes and identifies potentially
      targetable mechanisms for CMS treatment. 

PMID- 23954165
TI  - Flow velocities in the external carotid artery following carotid
      revascularization.
AB  - OBJECTIVE: To study the changes in peak systolic velocities of the ipsilateral
      external carotid artery (ECA) following carotid revascularization. METHODS: All
      patients randomized to carotid artery stenting (CAS) or carotid endarterectomy
      (CEA) in the International Carotid Stenting Study (ICSS; ISRCTN25337470) in our
      center were included. Peak systolic velocities (PSV) were assessed with duplex
      ultrasound (DUS) at baseline, at 30 days, and at 12 and 24 months after
      treatment. Our primary outcome measure was the change in blood flow velocities in
      the ECA (DeltaPSVECA). Secondary outcome measure was the prevalence of post
      interventional ECA occlusion. RESULTS: Of 270 patients enrolled in ICSS at our
      center, 224 patients (mean age, 68.8 years; 154 males) were included in the
      present study (116 CAS, 108 CEA). Baseline PSV in the ipsilateral ECA was similar
      between the groups. Following CAS, PSV gradually increased during follow-up,
      whereas PSV remained relatively stable after CEA; mean difference of PSV between
      CAS and CEA: 23 cm/s (95% CI, -5 to 52), 58 cm/s (95% CI, 27-89), and 69 cm/s
      (95% CI, 31-107) at 30 days, 12 months, and 24 months. One new ECA occlusion
      occurred after CAS and two after CEA. CONCLUSION: Blood flow velocities in the
      ipsilateral ECA increase significantly after CAS but not after CEA. However, this
      does not lead to a higher rate of ECA occlusion in the first 2 years after
      revascularization. We conclude that CAS is not inferior to CEA in preserving the
      ECA as a possible potential collateral pathway for cerebral blood supply within 2
      years following revascularization.

PMID- 23954167
TI  - The impact of superimposition choice in geometric morphometric approaches to
      morphological integration.

PMID- 23954166
TI  - Tear film mucins: front line defenders of the ocular surface; comparison with
      airway and gastrointestinal tract mucins.
AB  - The ocular surface including the cornea and conjunctiva and its overlying tear
      film are the first tissues of the eye to interact with the external environment.
      The tear film is complex containing multiple layers secreted by different glands
      and tissues. Each layer contains specific molecules and proteins that not only
      maintain the health of the cells on the ocular surface by providing nourishment
      and removal of waste products but also protect these cells from environment. A
      major protective mechanism that the corneal and conjunctival cells have developed
      is secretion of the innermost layer of the tear film, the mucous layer. Both the
      cornea and conjunctiva express membrane spanning mucins, whereas the conjunctiva
      also produces soluble mucins. The mucins present in the tear film serve to
      maintain the hydration of the ocular surface and to provide lubrication and anti
      adhesive properties between the cells of the ocular surface and conjunctiva
      during the blink. A third function is to contribute to the epithelial barrier to
      prevent pathogens from binding to the ocular surface. This review will focus on
      the different types of mucins produced by the corneal and conjunctival epithelia.
      Also included in this review will be a presentation of the structure of mucins,
      regulation of mucin production, role of mucins in ocular surface diseases, and
      the differences in mucin production by the ocular surface, airways and
      gastrointestinal tract. 

PMID- 23954168
TI  - Is CD69 an effective brake to control inflammatory diseases?
AB  - Early studies described CD69 as a leukocyte activation marker, and suggested its
      involvement in the activation of different leukocyte subsets as well as in the
      pathogenesis of chronic inflammation. However, recent investigations have showed
      that CD69 knockout mice exhibit an enhanced or reduced susceptibility to
      different experimental models of inflammatory diseases, including those mediated
      by T helper 17 (Th17) lymphocytes. In this regard, the expression of CD69, both
      in Th17 lymphocytes and by a subset of regulatory T cells, has an important role
      in the control of the immune response and the inflammatory phenomenon. Therefore,
      different evidence indicates that CD69 exerts a complex immunoregulatory role in
      humans, and that it could be considered as a target molecule for the therapy of
      immune-mediated diseases. 

PMID- 23954170
TI  - Nardilysin prevents amyloid plaque formation by enhancing alpha-secretase
      activity in an Alzheimer's disease mouse model.
AB  - Amyloid beta (Abeta) peptide, the main component of senile plaques in patients
      with Alzheimer's disease (AD), is derived from proteolytic cleavage of amyloid
      precursor protein (APP) by beta- and gamma-secretases. Alpha-cleavage of APP by
      alpha-secretase has a potential to preclude the generation of Abeta because it
      occurs within the Abeta domain. We previously reported that a
      metalloendopeptidase, nardilysin (N-arginine dibasic convertase; NRDc) enhances
      alpha-cleavage of APP, which results in the decreased generation of Abeta in
      vitro. To clarify the in vivo role of NRDc in AD, we intercrossed transgenic mice
      expressing NRDc in the forebrain with an AD mouse model. Here we demonstrate that
      the neuron-specific overexpression of NRDc prevents Abeta deposition in the AD
      mouse model. The activity of alpha-secretase in the mouse brain was enhanced by
      the overexpression of NRDc, and was reduced by the deletion of NRDc. However,
      reactive gliosis adjacent to the Abeta plaques, one of the pathological features
      of AD, was not affected by the overexpression of NRDc. Taken together, our
      results indicate that NRDc controls Abeta formation through the regulation of
      alpha-secretase.

PMID- 23954169
TI  - Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment
      additively improve redox glutathione levels and neuron survival in aging and
      Alzheimer mouse neurons upstream of reactive oxygen species.
AB  - To determine whether glutathione (GSH) loss or increased reactive oxygen species
      (ROS) are more important to neuron loss, aging, and Alzheimer's disease (AD), we
      stressed or boosted GSH levels in neurons isolated from aging 3xTg-AD neurons
      compared with those from age-matched nontransgenic (non-Tg) neurons. Here, using
      titrating with buthionine sulfoximine, an inhibitor of gamma-glutamyl cysteine
      synthetase (GCL), we observed that GSH depletion increased neuronal death of 3xTg
      AD cultured neurons at increasing rates across the age span, whereas non-Tg
      neurons were resistant to GSH depletion until old age. Remarkably, the rate of
      neuron loss with ROS did not increase in old age and was the same for both
      genotypes, which indicates that cognitive deficits in the AD model were not
      caused by ROS. Therefore, we targeted for neuroprotection activation of the redox
      sensitive transcription factor, nuclear erythroid-related factor 2 (Nrf2) by 18
      alpha glycyrrhetinic acid to stimulate GSH synthesis through GCL. This balanced
      stimulation of a number of redox enzymes restored the lower levels of Nrf2 and
      GCL seen in 3xTg-AD neurons compared with those of non-Tg neurons and promoted
      translocation of Nrf2 to the nucleus. By combining the Nrf2 activator together
      with the NADH precursor, nicotinamide, we increased neuron survival against
      amyloid beta stress in an additive manner. These stress tests and neuroprotective
      treatments suggest that the redox environment is more important for neuron
      survival than ROS. The dual neuroprotective treatment with nicotinamide and an
      Nrf2 inducer indicates that these age-related and AD-related changes are
      reversible. 

PMID- 23954171
TI  - Selective benefits of simvastatin in bitransgenic APPSwe,Ind/TGF-beta1 mice.
AB  - Cognitive and cerebrovascular deficits are 2 landmarks of Alzheimer's disease
      (AD) to target for effective therapy. Here, we evaluated the efficacy of
      simvastatin in bitransgenic A/T mice overexpressing a mutated form of the human
      amyloid precursor protein (APP(Swe,Ind)) and a constitutively active form of
      transforming growth factor-beta1. These mice feature the AD amyloid beta (Abeta)
      and cerebrovascular pathology. Simvastatin significantly decreased insoluble
      Abeta peptide levels and Abeta plaque load despite no effect on beta-site amyloid
      precursor protein-cleaving enzyme and Abeta-degrading enzyme neprilysin protein
      levels. However, simvastatin failed to improve spatial learning and memory
      deficits and the decreased baseline levels of the memory-related protein early
      growth response-1 (Egr-1) in the hippocampus CA1 area. The impaired hyperemic
      response to whisker stimulation in A/T mice was not improved with treatment, but
      simvastatin fully restored constitutive nitric oxide synthesis in vessel walls
      and exacerbated agonist-mediated dilatory deficits. These findings point to the
      efficacy of simvastatin on selective AD features in a complex model of the
      disease, likely reflecting the challenges faced by recent clinical trials in
      assessing statin efficacy.

PMID- 23954172
TI  - Accumulation of C-terminal fragments of transactive response DNA-binding protein
      43 leads to synaptic loss and cognitive deficits in human TDP-43 transgenic mice.
AB  - Accumulation of the transactive response DNA-binding protein 43 (TDP-43) is a
      major hallmark of several neurodegenerative disorders, collectively known as TDP
      43 proteinopathies. The most common TDP-43 proteinopathies, frontotemporal lobar
      degeneration with TDP-43-positive inclusions, and amyotrophic lateral sclerosis,
      share overlapping neuropathological and clinical phenotypes. The development and
      detailed analysis of animal models of TDP-43 proteinopathies are critical for
      understanding the pathogenesis of these disorders. Transgenic mice overexpressing
      mutant human TDP-43 (herein referred to as hTDP-43) are characterized by
      neurodegeneration and reduced life span. However, little is known about the
      behavioral phenotype of these mice. Here we report the novel finding that hTDP-43
      mice develop deficits in cognition, motor performance, and coordination. We show
      that these behavioral deficits are associated with the accumulation of nuclear
      and cytosolic TDP-43 C-terminal fragments, a decrease in endogenous TDP-43
      levels, and synaptic loss. Our findings provide critical insights into disease
      pathology, and will help guide future preclinical studies aimed at testing the
      effects of potential therapeutic agents on the onset and progression of TDP-43
      proteinopathies. 

PMID- 23954173
TI  - Novel SOD1 mutation p.V31A identified with a slowly progressive form of
      amyotrophic lateral sclerosis.
AB  - The SOD1 gene encoding the superoxide dismutase 1 (SOD1) protein is mutated in
      approximately 15% of familial amyotrophic lateral sclerosis (ALS) and 3% of
      sporadic ALS. We identified a novel mutation in SOD1 in a man who presented at
      age 49 with lower limb stiffness, and at age 53, a spastic paraparesia with
      distal muscular atrophy in the lower limbs and fasciculations in the quadriceps.
      A diagnosis of ALS was established. Eleven years after disease onset his
      condition continues gradually and slowly to deteriorate. The heterozygous
      mutation observed in exon 2 resulted in a valine to alanine substitution at
      position 31 in the beta-barrel domain of the SOD1 protein. Functional analysis in
      NSC34 cells showed that the overexpression of the mutant form of SOD1(V31A)
      induced aggregates and decreased cell viability. This mutation is located outside
      of the regions carrying most of the ALS-related mutations (i.e., the catalytic
      center, the region of dimerization, and the loops between the beta-strands of the
      beta-barrel). In conclusion, we identified a novel SOD1 mutation in a patient
      with slow disease progression and supported the idea that different SOD1
      mutations can lead to distinct ALS phenotypes. 

PMID- 23954174
TI  - Acute isolation and transcriptome characterization of cortical astrocytes and
      microglia from young and aged mice.
AB  - Astrocytes and microglia become reactive in many neurological disorders resulting
      in phenotypic and functional alterations. Both cell types might also display
      functional changes during normal aging. To identify gene signatures and changes
      in basal cellular functions of astrocytes and microglia in relation to aging, we
      isolated viable astrocytes and microglia from young adult and aged mouse cortices
      and determined their gene expression profile. Aged astrocytes, compared with
      young astrocytes, showed an increased inflammatory phenotype and increased 'zinc
      ion binding.' Young astrocytes showed higher expression of genes involved in
      'neuronal differentiation' and hemoglobin synthesis. Astrocyte expression of
      genes involved in neuronal signaling remains high throughout age. Aged microglia
      had higher expression of genes involved in 'vesicle release,' 'zinc ion binding,'
      and genes within the tumor necrosis factor-ligand family and young microglia had
      increased transcript levels of C-C motif chemokines. These data provide a
      transcriptome database of cell-type enriched genes of astrocytes and microglia
      from adult mice and give insight into the differential gene signature of
      astrocytes and microglia in relation to normal aging. 

PMID- 23954175
TI  - Comparison of neuroimaging modalities for the prediction of conversion from mild
      cognitive impairment to Alzheimer's dementia.
AB  - In this study we compared Pittsburgh compound-B (PIB) positron emission
      tomography (PET) amyloid imaging, fluorodeoxyglucose PET for metabolism, and
      magnetic resonance imaging (MRI) for structure to predict conversion from
      amnestic mild cognitive impairment (MCI) to Alzheimer's dementia using data from
      the Alzheimer's Disease Neuroimaging Initiative cohort. Numeric neuroimaging
      variables generated by the Alzheimer's Disease Neuroimaging Initiative-funded
      laboratories for each neuroimaging modality along with apolipoprotein-E genotype
      (n = 29) were analyzed. Performance of these biomarkers for predicting conversion
      from MCI to Alzheimer's dementia at 2 years was evaluated in 50 late amnestic MCI
      subjects, 20 of whom converted. Multivariate modeling found that among individual
      modalities, MRI had the highest predictive accuracy (67%) which increased by 9%
      to 76% when combined with PIB-PET, producing the highest accuracy among any
      biomarker combination. Individually, PIB-PET generated the best sensitivity, and
      fluorodeoxyglucose PET had the lowest. Among individual brain regions, the
      temporal cortex was found to be most predictive for MRI and PIB-PET.

PMID- 23954176
TI  - Some like it pungent and vile. TRPA1 as a molecular target for the malodorous
      vinyl disulfides from asafoetida.
AB  - Ferula assa-foetida L. is a major source of asafoetida, a foul-smelling gum-resin
      of dietary and medicinal relevance. Investigation of the roots and latex of F.
      assa-foetida yielded various mixed vinyl disulfides, including two novel
      asadisulfide-type esters. The reactivity of asadisulfide was investigated in the
      cysteamine NMR assay, where it behaved as disulfide shuffling agents due to the
      high mobility of the vinyl sulfide moiety. In accordance with their
      transthiolation capacity, these compounds potently activated TRPA1, the target of
      mustard oil and the pungent sulfur compounds from onion and garlic, qualifying S
      alkyl-S-alkenyldisulfides, a rare class of natural products, as a novel class of
      dietary TRPA1 activators. These observations provide a mechanistic basis for
      rationalizing some of the sensory properties and potential beneficial health
      claims associated to the use of asafoetida as a spice and as a medicine. 

PMID- 23954177
TI  - Ophiobolins P-T, five new cytotoxic and antibacterial sesterterpenes from the
      endolichenic fungus Ulocladium sp.
AB  - Five ophiobolane sesterterpenes, ophiobolins P-T, and three known compounds, 6
      epi-21,21-O-dihydroophiobolin G, 6-epi-ophiobolin G and 6-epi-ophiobolin K, were
      isolated from the acetone extract of the endolichenic fungus Ulocladium sp. by
      using OSMAC method. Their structures were elucidated on the basis of
      spectroscopic analysis. The absolute configuration of the 18,19-diol moieties in
      ophiobolin Q was assigned using the Frelek's method. The cytotoxic effects on KB
      and HepG2 cell lines, antibacterial activity against Bacillus subtilis,
      methicillin-resistant Staphylococcus aureus, and Bacille Calmette-Guerin were
      evaluated for all isolated compounds. Ophiobolin T and 6-epi-ophiobolin G
      exhibited the most potent cytotoxic activity against HepG2 with IC50 of 0.24 and
      0.37 MUM, respectively. In antibacterial assay, ophiobolins P and T showed
      moderate antibacterial activity against B. subtilis and meticillin-resistant S.
      aureus. Ophiobolin T also displayed moderate antibacterial activity against the
      Bacille Calmette-Guerin strain.

PMID- 23954178
TI  - Isolation of new flavan-3-ol and lignan glucoside from Loropetalum chinense and
      their antimicrobial activities.
AB  - Phytochemical and antimicrobial activity study on the ethanol extract of the
      leaves and stems of Loropetalum chinense led to the isolation of a new flavan-3
      ol compounds, 8-[1-(3,4-dihydroxyphenyl)-3-methoxy-3-oxopropyl]-catechin
      (loropetaliside A) (1) and a new lignan glucoside, 1-(5-hydroxy-3-methoxyphenyl)
      2-(2-beta-glucopyranosyl-4-hydroxy-5-(1-(E)propen-3-ol)-phenyl)-propane-3-ol
      (loropetaliside B) (3) and several known compounds manglieside D (2), quercetin
      (4), kaempferol-3-O-D-glucopyranoside (5), quercetin-3-O-beta-L-rhamnoside (6)
      and tiliroside (7). Their structures were elucidated on the basis of extensive
      spectroscopic analysis. 

PMID- 23954179
TI  - Pivotal role of microRNAs in cardiac physiology and heart failure.
AB  - Cardiac hypertrophy is a hallmark of heart failure (HF), a highly prevalent,
      debilitating and deadly condition in Western countries. Pronounced changes in
      molecular pathways governing cardiac physiology underlie hypertrophy and
      progression to HF. MicroRNAs, small nucleotide sequences that coordinate gene
      expression, may have a central role in orchestrating these changes since the
      hypertrophic and HF myocardium clearly shows disturbed microRNA profiles.
      Experimental interventions targeting miR disturbances have been shown beneficial
      in animal models of cardiac hypertrophy and HF. This short review discusses
      exciting potential diagnostic and therapeutic applications of microRNAs to
      cardiac hypertrophy and HF, highlighting the underlying molecular pathways. 

PMID- 23954180
TI  - Immunity and Alzheimer's disease: immunological perspectives on the development
      of novel therapies.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder among
      older people. However, no cure or disease-modifying treatments are currently
      available, and the molecular and cellular mechanisms responsible for the etiology
      of AD remain under debate. Recent studies suggest that the immune system has a
      crucial role in AD pathogenesis and, thus, immunotherapy might be a promising new
      treatment. Here, we review the roles of the immune system in AD pathogenesis as
      well as recent developments in immunotherapy for AD. Furthermore, we hypothesize
      that age-related immune dysregulation, which might be a consequence of the age
      associated chronic inflammation known as 'inflammaging', significantly
      contributes to AD pathogenesis. Finally, we propose various immunological
      mechanisms for the development of safe and effective therapies for AD. 

PMID- 23954181
TI  - Triterpenoids as reversal agents for anticancer drug resistance treatment.
AB  - Overexpression of ATP-binding cassette (ABC) transporters in cancer cells results
      in multidrug resistance (MDR), which is one of the major obstacles in the
      treatment of cancer patients. None of the strategies to overcome MDR has been
      successfully applied in the clinic until now. Plenty of evidence shows that some
      triterpenoids function as reversal agents of MDR for anticancer drug resistance
      treatment. Here, we review the latest findings of reversing cancer MDR with
      triterpenoids. Findings are summarized showing that triterpenoids are MDR
      modulators and potential chemosensitizers. Finally, we contemplate future
      prospects of modulating MDR in the clinic. 

PMID- 23954182
TI  - Development and evaluation of the Motivation to Limit Screen-time Questionnaire
      (MLSQ) for adolescents.
AB  - OBJECTIVE: The aim of this study was to design and evaluate a brief scale to
      assess adolescents' motivation to limit their screen-time using a self
      determination theory (SDT) framework. METHODS: The development and evaluation of
      the Motivation to Limit Screen-time Questionnaire (MLSQ) involved three phases.
      In Phase 1, experts in SDT were asked to review the content validity of the MLSQ
      items. In Phase 2, adolescent boys (N=342, mean age=12.7 +/-.5 years) completed
      the MLSQ and the factorial validity of the model was explored. In Phase 3,
      adolescent boys (N=48, mean age=14.3 +/- 1.3 years) completed the MLSQ on two
      occasions separated by 1-week. Phases 2 and 3 were conducted in New South Wales,
      Australia in 2012. RESULTS: Twenty four SDT experts reviewed the original scale
      items. Validity coefficients associated with six of the original eight items
      exceeded the threshold value (V>.68, p<.01). In Phase 2, the revised three-factor
      (9-items) model provided a good fit to the data (SRMR=.07, CFI=.96). The
      intraclass correlation (ICC) values were .67 for amotivation and .70 and .82 for
      controlled and autonomous motivation, respectively. CONCLUSION: This study has
      provided preliminary evidence for the validity and reliability of the MLSQ in
      adolescent boys.

PMID- 23954183
TI  - Impact of the UK voluntary sodium reduction targets on the sodium content of
      processed foods from 2006 to 2011: analysis of household consumer panel data.
AB  - OBJECTIVE: In 2006 the UK Food Standards Agency (FSA) introduced voluntary sodium
      reduction targets for more than 80 categories of processed food. Our aim was to
      determine the impact of these targets on the sodium content of processed foods in
      the UK between 2006 and 2011. METHOD: Household consumer panel data (n>18,000
      households) were used to calculate crude and sales-weighted mean sodium content
      for 47,337 products in 2006 and 49,714 products in 2011. Two sample t-tests were
      used to compare means. A secondary analysis was undertaken to explore
      reformulation efforts and included only products available for sale in both 2006
      and 2011. RESULTS: Between 2006 and 2011 there was an overall mean reduction in
      crude sodium content of UK foods of -26 mg/100g (p <= 0.001), equivalent to a 7%
      fall (356 mg/100g to 330 mg/100g). The corresponding sales-weighted reduction was
      -21 mg/100g (-6%). For products available for sale in both years the
      corresponding reduction was -23 mg/100g (p<0.001) or -7%. CONCLUSION: The UK FSA
      voluntary targets delivered a moderate reduction in the mean sodium content of UK
      processed foods between 2006 and 2011. Whilst encouraging, regular monitoring and
      review of the UK sodium reduction strategy will be essential to ensure continued
      progress.

PMID- 23954184
TI  - GoWell: the challenges of evaluating regeneration as a population health
      intervention.
AB  - OBJECTIVE: Urban regeneration can be considered a population health intervention
      (PHI). It is expected to impact on population health but the evidence is limited
      or weak, in part due to the difficulties of evaluating PHIs. We explore these
      challenges using GoWell as a case study. METHOD: A 10-year evaluation of housing
      improvement and urban regeneration in 15 deprived areas in Glasgow, Scotland
      (2005-2015). RESULTS: Challenges faced include: definition and changing nature of
      the intervention; identifying the recipients of the intervention; and constraints
      of study design affecting capacity to attribute effects. We have met these
      challenges by: adapting the evaluation to take account of changing intervention
      plans and delivery; making pragmatic choices about which populations to focus on
      for different parts of the study; and taking advantage of delayed delivery of
      some components to identify controls. CONCLUSION: Commitment to a long-term
      evaluation by the Scottish Government and other partners has enabled us to
      develop a package of studies to investigate health and other outcomes, and the
      processes of a PHI. GoWell will contribute to the evidence base for interventions
      focused on tackling the wider determinants of health and help policymakers to be
      more explicit and realistic about what regeneration might achieve.

PMID- 23954185
TI  - Dose-response association of physical activity with acute myocardial infarction:
      do amount and intensity matter?
AB  - OBJECTIVE: The aims of this study were to analyze the dose-response association
      between leisure time physical activity (PA) practice and myocardial infarction
      (MI), considering not only the total amount but also the amount of PA at
      different levels of intensity, and to determine whether these associations were
      modified by age. METHOD: In a population-based age- and sex-matched case-control
      study, all first acute MI patients aged 25 to 74 years were prospectively
      registered in four Spanish hospitals between 2002 and 2004. Controls were
      randomly selected from population-based samples recruited during the same period
      of time. The Minnesota PA questionnaire was administered to assess total energy
      expenditure in PA and in light-, moderate-, and high-intensity PA. RESULTS:
      Finally, 1339 cases and 1339 controls were included. The association between PA
      and MI likelihood was non-linear, with significantly lower MI odds at low
      practice levels (>= 500 MET.min/week), lowest odds around 1500 MET.min/week, and
      a plateau thereafter. Light- (in subjects older than 64 years), moderate-, and
      high-intensity PA produced similar benefits. CONCLUSION: Most of the population
      could reduce their likelihood of MI by engaging in PA at a moderate level of
      intensity or, in individuals older than 64 years, at a light level of intensity.

PMID- 23954186
TI  - Lead time and down-staging in the survival of cervical cancer cases detected by
      screening.

PMID- 23954187
TI  - Prevention of human papillomavirus-related diseases: Impediments to progress.

PMID- 23954188
TI  - Re: lead time and down-staging in the survival of cervical cancer cases detected
      by screening.

PMID- 23954189
TI  - Secondary structure prediction for complete rDNA sequences (18S, 5.8S, and 28S
      rDNA) of Demodex folliculorum, and comparison of divergent domains structures
      across Acari.
AB  - According to base pairing, the rRNA folds into corresponding secondary
      structures, which contain additional phylogenetic information. On the basis of
      sequencing for complete rDNA sequences (18S, ITS1, 5.8S, ITS2 and 28S rDNA) of
      Demodex, we predicted the secondary structure of the complete rDNA sequence (18S,
      5.8S, and 28S rDNA) of Demodex folliculorum, which was in concordance with that
      of the main arthropod lineages in past studies. And together with the sequence
      data from GenBank, we also predicted the secondary structures of divergent
      domains in SSU rRNA of 51 species and in LSU rRNA of 43 species from four
      superfamilies in Acari (Cheyletoidea, Tetranychoidea, Analgoidea and Ixodoidea).
      The multiple alignment among the four superfamilies in Acari showed that,
      insertions from Tetranychoidea SSU rRNA formed two newly proposed helixes, and
      helix c3-2b of LSU rRNA was absent in Demodex (Cheyletoidea) taxa. Generally
      speaking, LSU rRNA presented more remarkable differences than SSU rRNA did,
      mainly in D2, D3, D5, D7a, D7b, D8 and D10. 

PMID- 23954190
TI  - Efficacy of a single intravenous administration of laninamivir (an active
      metabolite of laninamivir octanoate) in an influenza virus infection mouse model.
AB  - Laninamivir, a potent neuraminidase (NA) inhibitor, is an active metabolite of
      laninamivir octanoate (code name: CS-8958) which is a long acting NA inhibitor
      and is commercially available under the brand name Inavir in Japan to complete
      the treatment of influenza by a single inhalation. It is supposed that the long
      acting character is provided by the long retention of laninamivir in the
      respiratory tract after intranasal administration of laninamivir octanoate in
      mice and with stable binding of laninamivir to NA of various influenza viruses
      such as N1, N2 subtypes and NA of B virus. Peramivir, another NA inhibitor, is
      also approved in Japan as a single intravenous infusion. In spite of the quick
      disappearance of peramivir from the blood after injection, the reason treatment
      can be completed by a single administration is thought to be that peramivir
      showed stable binding to NA with N9 subtype. Therefore, the stable binder,
      laninamivir is possibly effective by a single intravenous administration in the
      mouse model infected with influenza viruses. A single intravenous administration
      of laninamivir and peramivir at 30mg/kg significantly prolonged mice survival at
      a comparable level in the mouse lethal model infected with the A/PR/8/34 (H1N1)
      virus. Also, a single intravenous administration of laninamivir and peramivir
      significantly suppressed virus proliferation in the lungs of mice infected with
      influenza B virus. Thus, laninamivir may be effective by a single intravenous
      infusion in treating influenza, the same as peramivir. 

PMID- 23954191
TI  - Overexpression of microRNA gga-miR-21 in chicken fibroblasts suppresses
      replication of infectious bursal disease virus through inhibiting VP1
      translation.
AB  - Previously we have identified a series of cellular miRNA molecules up- or down
      regulated in infectious bursal disease virus (IBDV) infected chicken embryo
      fibroblasts and Bursa of Fabricius with gene microarray analysis. Here we studied
      in detail a relatively well studied miRNA, gga-miR-21, for better understanding
      miRNAs involvement in IBDV-host interactions. Chicken pri-gga-miRNA-21 and a
      control miRNA Caenorhabditis elegans pri-cel-lin-4 gene were cloned into a
      lentiviral vector, respectively. The resulting recombinant lentiviruses were used
      to infect chicken fibroblast cell line DF-1, and two stable cell lines, DF-miR-21
      (overexpressing gga-miR-21) and DF-lin-4 (overexpressing cel-lin-4), were
      selected. Replication of IBDV in DF-miR-21, DF-lin-4 and DF-1 cells were compared
      and molecular mechanism of IBDV replication alteration was explored using
      bioinformatics, reporter gene system, qRT-PCR and Western blot analysis. IBDV
      replication was markedly lower in DF-miR-21 than in DF-lin-4 or DF-1 cells. A gga
      miR-21 target sequence was identified within IBDV VP1 gene (1713-1734bp). Fusion
      of a 520nt long partial IBDV VP1 gene containing the target with a luciferase
      gene resulted in significantly lower transient luciferase activity in DF-miR-21
      cells as compared to that in DF-lin-4 or DF-1 cell. Following IBDV infection of
      the cell lines, VP1 protein level in DF-miR-21 cells was dramatically lower than
      that in DF-lin-4 or DF-1 cells but VP1 mRNA level was not different. The finding
      indicated that gga-miR-21 could suppress IBDV replication through down regulating
      IBDV VP1 expression at translational level. 

PMID- 23954192
TI  - Inhibition of influenza virus internalization by (-)-epigallocatechin-3-gallate.
AB  - (-)-Epigallocatechin-3-gallate (EGCG), one of the major flavonoid components of
      green tea, is known to have a broad antiviral activity against several enveloped
      viruses, including the influenza virus. However, its mode of action and the
      mechanism that allows it to target influenza virus molecules have not been fully
      elucidated. Thus, this study investigated the molecular mechanism by which EGCG
      suppresses influenza virus infections. EGCG was found to block an early step in
      the influenza viral life cycle, but it did not affect viral adsorption to target
      cells or viral RNA replication. However, EGCG inhibited hemifusion events between
      virus particles and the cellular membrane by reducing the viral membrane
      integrity, thereby resulting in the loss of the cell penetration capacity of the
      influenza virus. EGCG also marginally suppressed the viral and nonviral
      neuraminidase (NA) activity in an enzyme-based assay system. In conclusion, it is
      suggested that the anti-influenza viral efficacy of EGCG is attributable to
      damage to the physical properties of the viral envelope and partial inhibition of
      the NA surface glycoprotein. These results may facilitate future investigations
      of the antiviral activity of EGCG against other enveloped viruses as well as
      influenza virus. 

PMID- 23954194
TI  - Bladder autoaugmentation (partial detrusor myectomy)--where does it stand after 2
      decades?

PMID- 23954195
TI  - Positive fantasies or negative contrasts: the effect of media body ideals on
      restrained eaters' mood, weight satisfaction, and food intake.
AB  - Although viewing media body ideals promotes body dissatisfaction and problematic
      eating among women (e.g., extreme restraint/overeating), some argue that women
      only report such negative effects because they think that they are meant to
      (i.e., demand characteristics). Because restrained eaters are trying to lose
      weight, they might be vulnerable to such media exposure. However, because of
      demand characteristics, evidence is mixed. Therefore, we minimized demand
      characteristics and explored whether media body ideals would trigger restrained
      eaters to report negative (negative mood, weight dissatisfaction) or positive
      (positive mood, weight satisfaction) effects. We also hypothesized that this
      change (negative or positive) would encourage food intake. Restrained and
      unrestrained eaters (n=107) memorized media or control images. Restrained eaters
      exposed to media images reported decreased weight satisfaction and increased
      negative mood, but their food intake was not significantly affected. Perhaps
      paying advertent attention to the images caused goal-related negative affect,
      which triggered restraint. 

PMID- 23954196
TI  - Body appreciation in adult women: relationships with age and body satisfaction.
AB  - The major aim of the present study was to investigate the effect of age on
      positive body image (operationalized as body appreciation) across the female
      lifespan. A secondary aim was to examine the effect of age on the relationship
      between positive body image and body satisfaction. Participants were 158 women
      aged between 18 and 75 years who completed questionnaire measures of body
      appreciation and body dissatisfaction-satisfaction. A significant positive linear
      relationship was found between age and body appreciation; that is, older women
      had higher levels of body appreciation than their younger counterparts. Although
      body appreciation was positively correlated with body dissatisfaction
      satisfaction across all age groups, the association was weaker for older women.
      The results contribute to a richer picture of women's body image across the
      lifespan, as well as confirming positive body image as something beyond the mere
      absence of body dissatisfaction. 

PMID- 23954197
TI  - Social dominance orientation predicts drive for muscularity among British men.
AB  - The present study tested the hypothesis that men's drive for muscularity would be
      associated with their valuation of domination, power, status, and aggression over
      others. A community sample of 359 men from London, UK, completed measures of
      drive for muscularity, social dominance orientation, right-wing authoritarianism,
      trait aggression, and need for power, as well as their demographic details.
      Bivariate correlations showed that greater drive for muscularity was
      significantly correlated with most of the measures and their subscales. However,
      in a multiple regression analysis, the only significant predictor of drive for
      muscularity was support for group-based dominance hierarchies (Adj. R(2)=.17).
      These results suggest that men's drive for muscularity is associated with a socio
      political ideology that favours social dominance. 

PMID- 23954198
TI  - Synthesis of novel lipidated iridoid glycosides as vaccine adjuvants: 6-O
      palmitoyl Agnuside elicit strong Th1 and Th2 response to ovalbumin in mice.
AB  - Novel lipidated analogs of iridoids viz., Agnuside and Negundoside with different
      chain length were synthesized and tested for immune adjuvant activity in the
      presence of weak antigen ovalbumin. Based on in vitro assay, 6-O-palmitoyl
      Agnuside (AG-3) was further taken up for detailed in vivo activity and found to
      significantly enhance the production of anti OVA IgG titer, neutralizing antibody
      (IgG1 and IgG2a) titer as well as soluble mediators of a Th1 (IL-2, IFN
      gamma)/Th2 response (IL-4) and proliferation of T lymphocyte subsets (CD4/CD8)
      and co stimulatory molecules CD80/CD86. Furthermore, the SAR studies revealed
      that presence of acyl group at aglycon moiety of these iridoid glycosides is
      crucial for immune adjuvant activity. 

PMID- 23954199
TI  - Structure-activity relationships for perfluoroalkane-induced in vitro
      interference with rat liver mitochondrial respiration.
AB  - Perfluorinated alkyl acids (PFAAs) represent a broad class of commercial products
      designed primarily for the coatings industry. However, detection of residues
      globally in a variety of species led to the discontinuation of production in the
      U.S. Although PFAAs cause activation of the PPARalpha and CAR nuclear receptors,
      interference with mitochondrial bioenergetics has been implicated as an
      alternative mechanism of cytotoxicity. Although the mechanisms by which the eight
      carbon chain PFAAs interfere with mitochondrial bioenergetics are fairly well
      described, the activities of the more highly substituted or shorter chain PFAAs
      are far less well characterized. The current investigation was designed to
      explore structure-activity relationships by which PFAAs interfere with
      mitochondrial respiration in vitro. Freshly isolated rat liver mitochondria were
      incubated with one of 16 different PFAAs, including perfluorinated carboxylic,
      acetic, and sulfonic acids, sulfonamides and sulfamido acetates, and alcohols.
      The effect on mitochondrial respiration was measured at five concentrations and
      dose-response curves were generated to describe the effects on state 3 and 4
      respiration and respiratory control. With the exception of PFOS, all PFAAs at
      sufficiently high concentrations (>20MUM) stimulated state 4 and inhibited state
      3 respiration. Stimulation of state 4 respiration was most pronounced for the
      carboxylic acids and the sulfonamides, which supports prior evidence that the
      perfluorinated carboxylic and acetic acids induce the mitochondrial permeability
      transition, whereas the sulfonamides are protonophoric uncouplers of oxidative
      phosphorylation. In both cases, potency increased with increasing carbon number,
      with a prominent inflection point between the six and eight carbon congeners. The
      results provide a foundation for classifying PFAAs according to specific modes of
      mitochondrial activity and, in combination with toxicokinetic considerations,
      establishing structure-activity-based boundaries for initial estimates of risk
      for noncancer endpoints for PFAAs for which minimal in vivo toxicity testing
      currently exists. 

PMID- 23954200
TI  - Renal biomarkers predict nephrotoxicity after paraquat.
AB  - Paraquat is a widely used herbicide which has been involved in many accidental
      and intentional deaths. Nephrotoxicity is common in severe acute paraquat
      poisoning. We examined seven renal injury biomarkers, including cystatin-C,
      kidney injury molecule-1, beta2-microglobulin, clusterin, albumin, neutrophil
      gelatinase-associated lipocalin and osteopontin, to develop a non-invasive method
      to detect early renal damage and dysfunction and to compare with the conventional
      endogenous marker creatinine. Male Wistar rats were dosed orally with four
      different doses of paraquat, and the biomarker patterns in urine and plasma were
      investigated at 8, 24 and 48h after paraquat exposure. By Receiver Operating
      Characteristic analysis, urinary kidney injury molecule-1 was the best marker at
      predicting histological changes, with areas under the Receiver Operating
      Characteristic curve of 0.81 and 0.98 at 8 and 24h (best cut-off
      value>0.000326MUg/ml), respectively. Urinary kidney injury molecule-1, urinary
      albumin and urinary Cystatin-C elevations correlated with the degree of renal
      damage and injury development. Further study is required to compare biomarkers
      changes in rats with those seen in human poisoning. 

PMID- 23954201
TI  - The number of involved extracranial organs: a new predictor of survival in breast
      cancer patients with brain metastasis.
AB  - OBJECTIVE: This study was performed to investigate the potential impact of the
      number of involved extracranial organs on survival in patients with brain
      metastasis from breast cancer. METHODS: The data of 196 patients treated with
      whole-brain radiotherapy (WBRT) alone for brain metastases from breast cancer
      were retrospectively analyzed. Six potential prognostic factors were evaluated
      for associations with survival. These factors included WBRT regimen, age,
      Karnofsky performance score (KPS), number of brain metastases, interval from
      breast cancer diagnosis to WBRT, and the number of involved extracranial organs.
      RESULTS: The 6-month survival rates of patients with involvement of 0, 1, 2, 3
      and >=4 extracranial organs were 59%, 49%, 26%, 26% and 13%, respectively, and
      the 12-month survival rates were 45%, 36%, 17%, 17% and 13%, respectively
      (p<0.001). On multivariate analysis, the number of involved extracranial organs
      (risk ratio 1.17; 95%-confidence interval 1.02-1.35; p=0.028) maintained
      significance, as did KPS (p<0.001), but not age (p=0.27). CONCLUSION: The number
      of involved extracranial organs is an independent prognostic factor of survival
      in patients with brain metastasis from breast cancer.

PMID- 23954202
TI  - Intracavernous internal carotid artery mycotic aneurysms: comprehensive review
      and evaluation of the role of endovascular treatment.
AB  - Mycotic aneurysms may arise in the setting of many local or systemic infections.
      Those of the intracranial circulation are especially worrisome due to their
      potential to compress vital neural structures and their propensity for rupture
      with consequent hemorrhage. Mycotic aneurysms of the intracavernous internal
      carotid artery (ICA) represent an exceedingly rare clinical entity, described in
      less than fifty published cases. Typically presenting as a cavernous sinus
      syndrome with signs and symptoms of the underlying infection, they are often
      missed initially, with diagnosis and treatment commencing for the triggering
      infection or confused with cavernous sinus thrombophlebitis, which may be
      additionally coexistent, confounding timely diagnosis of the aneurysmal disease.
      Compared to non-mycotic aneurysms of the intracavernous ICA, which typically have
      a benign course, the infectious etiology of the mycotic variety increases their
      tendency to rupture, precludes surgical clipping as a viable treatment option,
      and requires institution of prolonged antibiotic therapy prior to definitive
      intervention. Their critical location, friability, and propensity to occur
      bilaterally result in an unpredictable risk of rapid neurological decline and
      death, making the timing and specific nature of treatment a unique dilemma facing
      the treating physician. This review seeks to discuss the natural history of and
      management strategies for mycotic aneurysms of the intracavernous ICA with
      special emphasis on the role, safety, and efficacy of endovascular therapies. 

PMID- 23954203
TI  - The transcriptional co-repressor TLE3 regulates development of trophoblast giant
      cells lining maternal blood spaces in the mouse placenta.
AB  - TLE3 is a transcriptional co-repressor that interacts with several DNA-binding
      repressors, including downstream effectors of the Notch signaling pathway. We
      generated Tle3-deficient mice and found that they die in utero and their death is
      associated with abnormal development of the placenta with major defects in the
      maternal vasculature. In the normal placenta, maternal blood spaces are lined,
      not as usual in the mammalian circulation by endothelial cells, but rather by
      specialized embryo-derived cells of the trophoblast cell lineage named
      trophoblast giant cells (TGC). Tle3 mRNA is expressed in those specialized TGC
      and Tle3 mutants show severe defects in differentiation of TGC-lined channels and
      lacunar spaces that take blood out of the labyrinth zone of the placenta and into
      the uterine veins. The mutants also show somewhat milder defects on the arterial
      side of the maternal vascular circuit in spiral arteries and canals that take
      blood into the labyrinth. Notch2 and Tle3 expression patterns overlap in several
      TGC subtypes and we found that Tle3 and Notch2 mutants have some overlapping
      features. However, they also show differences implying that TLE3 may mediate some
      but not all of the effects of Notch2 signaling during placenta development.
      Therefore, formation of the different types of maternal blood spaces by different
      TGC subtypes is regulated by distinct molecular mechanisms.

PMID- 23954204
TI  - Design and discovery of novel quinazolinedione-based redox modulators as
      therapies for pancreatic cancer.
AB  - BACKGROUND: Altered cellular bioenergetics and oxidative stress are emerging
      hallmarks of most cancers including pancreatic cancer. Elevated levels of
      intrinsic reactive oxygen species (ROS) in tumors make them more susceptible to
      exogenously induced oxidative stress. Excessive oxidative insults overwhelm their
      adaptive antioxidant capacity and trigger ROS-mediated cell death. Recently, we
      have discovered a novel class of quinazolinediones that exert their cytotoxic
      effects by modulating ROS-mediated signaling. METHODS: Cytotoxic potential was
      determined by colorimetric and colony formation assays. An XF24 Extracellular
      Flux Analyzer, and colorimetric and fluorescent techniques were used to assess
      the bioenergetics and oxidative stress effects, respectively. Mechanism was
      determined by Western blots. RESULTS: Compound 3a (6-[(2
      acetylphenyl)amino]quinazoline-5,8-dione) was identified through a medium
      throughput screen of ~1000 highly diverse in-house compounds and chemotherapeutic
      agents for their ability to alter cellular bioenergetics. Further structural
      optimizations led to the discovery of a more potent analog, 3b (6-[(3
      acetylphenyl)amino]quinazoline-5,8-dione) that displayed anti-proliferative
      activities in low micromolar range in both drug-sensitive and drug-resistant
      cancer cells. Treatment with 3b causes Akt activation resulting in increased
      cellular oxygen consumption and oxidative stress in pancreatic cancer cells.
      Moreover, oxidative stress induced by 3b promoted activation of stress kinases
      (p38/JNK) resulting in cancer cell death. Treatment with antioxidants was able to
      reduce cell death confirming ROS-mediated cytotoxicity. CONCLUSION: In
      conclusion, our novel quinazolinediones are promising lead compounds that
      selectively induce ROS-mediated cell death in cancer cells and warrant further
      preclinical studies. GENERAL SIGNIFICANCE: Since 3b (6-[(3
      acetylphenyl)amino]quinazoline-5,8-dione) exerts Akt-dependent ROS-mediated cell
      death, it might provide potential therapeutic options for chemoresistant and Akt
      overexpressing cancers.

PMID- 23954205
TI  - Reduced glycerol incorporation into phospholipids contributes to impaired intra
      erythrocytic growth of glycerol kinase knockout Plasmodium falciparum parasites.
AB  - BACKGROUND: Malaria is a devastating disease and Plasmodium falciparum is the
      most lethal parasite infecting humans. Understanding the biology of this parasite
      is vital in identifying potential novel drug targets. During every 48-hour intra
      erythrocytic asexual replication cycle, a single parasite can produce up to 32
      progeny. This extensive proliferation implies that parasites require substantial
      amounts of lipid precursors for membrane biogenesis. Glycerol kinase is a highly
      conserved enzyme that functions at the interface of lipid synthesis and
      carbohydrate metabolism. P. falciparum glycerol kinase catalyzes the ATP
      dependent phosphorylation of glycerol to glycerol-3-phosphate, a major
      phospholipid precursor. METHODS: The P. falciparum glycerol kinase gene was
      disrupted using double crossover homologous DNA recombination to generate a
      knockout parasite line. Southern hybridization and mRNA analysis were used to
      verify gene disruption. Parasite growth rates were monitored by flow cytometry.
      Radiolabelling studies were used to assess incorporation of glycerol into
      parasite phospholipids. RESULTS: Disruption of the P. falciparum glycerol kinase
      gene produced viable parasites, but their growth was significantly reduced to
      56.5+/-1.8% when compared to wild type parasites. (14)C-glycerol incorporation
      into the major phospholipids of the parasite membrane, phosphatidylcholine and
      phosphatidylethanolamine, was 48.4+/-10.8% and 53.1+/-5.7% relative to an
      equivalent number of wild type parasites. CONCLUSIONS: P. falciparum glycerol
      kinase is required for optimal intra-erythrocytic asexual parasite development.
      Exogenous glycerol may be used as an alternative carbon source for P. falciparum
      phospholipid biogenesis, despite the lack of glycerol kinase to generate glycerol
      3-phosphate. GENERAL SIGNIFICANCE: These studies provide new insight into
      glycerolipid metabolism in P. falciparum.

PMID- 23954206
TI  - Aquaporins in salivary glands and pancreas.
AB  - BACKGROUND: Salivary glands and pancreas are involved in saliva secretion,
      pancreatic fluid secretion and insulin secretion. These functions are essential
      for proper oral, pancreatic and glucose homeostasis. Aquaporins are water
      permeable transmembrane protein involved in the physiology of these secretory
      gland functions. SCOPE OF REVIEW: This review gives an overview of the morphology
      of salivary glands and pancreas, the expression and localization of aquaporins,
      the secretion roles and mechanisms, the physiological roles of aquaporins, and
      the role of aquaporins in pathophysiological conditions. MAJOR CONCLUSIONS:
      Several aquaporins are expressed in salivary glands and pancreas, and some play
      important physiological roles. Modulation of aquaporin expression and/or
      trafficking may contribute to the pathogenesis of diseases affecting salivary
      glands and pancreas glands such as xerostomic conditions, pancreatic
      insufficiencies and diabetes. GENERAL SIGNIFICANCE: Aquaporins are involved in
      physiological and pathophysiological processes in salivary glands and pancreas.
      They could represent therapeutic targets for the treatment of diseases affecting
      the salivary glands and pancreas. This article is part of a Special Issue
      entitled Aquaporins.

PMID- 23954207
TI  - Regulation of 15-hydroxyprostaglandin dehydrogenase expression in hepatocellular
      carcinoma.
AB  - Cyclooxygenase-2 (COX-2), a rate limiting step in arachidonic acid cascade, plays
      a key role in the biosynthesis of prostaglandin E2 (PGE2) upon inflammatory
      stimuli, growth factors, hormones and other cellular stresses. Overproduction of
      PGE2 stimulates proliferation of various cancer cells, confers resistance to
      apoptosis and favors metastasis and angiogenesis. The steady-state level of PGE2
      is maintained by interplay between the biosynthetic pathway including COX and
      PGE2 synthases and the catabolic pathways involving nicotinamide adenine
      dinucleotide (NAD(+))-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH).
      15-PGDH is a crucial enzyme responsible for the biological inactivation of PGE2.
      Adult hepatocytes fail to induce COX-2 expression regardless of the pro
      inflammatory factors used. COX-2 is induced in hepatocytes after partial
      hepatectomy (PH), in animal models of cirrhosis, in human hepatoma cell lines, in
      human HCC and after HBV and HCV infection. However, no data are available
      regarding 15-PGDH expression in HCC. Our results show that 15-PGDH is
      downregulated in human hepatoma cells with a high COX-2 expression, in chemical
      and genetic murine models of HCC and in human HCC biopsies. Moreover, 15-PGDH
      expression is suppressed by EGF (epidermal growth factor) and HGF (hepatocyte
      growth factor) mainly involving PI3K (phosphatidylinositol-3-kinase), ERK
      (extracellular signal-regulated kinase) and p38MAPK (mitogen-activated protein
      kinase) activation. Conversely, ectopic expression of 15-PGDH induces apoptosis
      in hepatoma cells and decreases the growth of hepatoma cells in nude mice whereas
      the silencing of 15-PGDH increases the tumor formation. These data suggest a
      potential therapeutic application of 15-PGDH in HCC. 

PMID- 23954208
TI  - Novel 2-(substituted benzyl)quinuclidines inhibit human alpha7 and alpha4beta2
      nicotinic receptors by different mechanisms.
AB  - This work presents the design and synthesis of a series of novel 2
      benzylquinuclidine derivatives, comprising 12 methiodide and 11 hydrochloride
      salts, and their structural and pharmacological characterization at the human (h)
      alpha7 and alpha4beta2 nicotinic receptors (nAChRs). The antagonistic potency of
      these compounds was tested by Ca(2+) influx assays on cells expressing the
      halpha7 or halpha4beta2 nAChR subtype. To determine the inhibitory mechanisms,
      additional radioligand binding experiments were performed. The results indicate
      that the methiodides present the highest affinities for the halpha7 nAChR agonist
      sites, while the same compounds bind preferably to the halpha4beta2 nAChR ion
      channel domain. These results indicate that the methiodides are competitive
      antagonists of the halpha7 nAChR but noncompetitive antagonists of the
      halpha4beta2 subtype. Docking and molecular dynamics simulations showed that the
      methiodide derivative 8d binds to the halpha7 orthosteric binding sites by
      forming stable cation-pi interactions between the quaternized quinulinuim moiety
      and the aromatic box in the receptor, whereas compounds 7j and 8j block the
      halpha4beta2 AChR ion channel by interacting with a luminal domain formed between
      the serine (position 6') and valine (position 13') rings that overlaps the
      imipramine binding site. 

PMID- 23954209
TI  - Clinical results of ab interno trabeculotomy using the trabectome for open-angle
      glaucoma: the Mayo Clinic series in Rochester, Minnesota.
AB  - PURPOSE: To determine outcomes of ab interno trabeculotomy for treatment of open
      angle glaucoma (OAG). DESIGN: Retrospective interventional single-surgeon, single
      center case series. METHODS: Data were collected from 246 patients undergoing ab
      interno trabeculotomy between September 1, 2006, and December 1, 2010, with 3
      months' follow-up or longer. Kaplan-Meier analysis was performed using Criteria A
      (postoperative intraocular pressure [IOP] <=21 mm Hg or >=20% reduction from
      preoperative IOP) and Criteria B (IOP <=18 mm Hg and >=20% reduction in IOP).
      Failure included increased glaucoma medications or subsequent surgery. Failure
      risk factors were identified using Cox proportional hazards ratio (HR). RESULTS:
      Of 88 cases of ab interno trabeculotomy-only and 158 cases of ab interno
      trabeculotomy with cataract extraction, the retention rate was 70% for 1 year and
      62% for 2 years. Preoperative mean IOP was 21.6 +/- 8.6 mm Hg; the number of
      glaucoma medications was 3.1 +/- 1.1. At 24 months postoperatively, mean IOP was
      reduced 29% to 15.3 +/- 4.6 mm Hg (P < 0.001) and the number of glaucoma
      medications was reduced 38% to 1.9 +/- 1.3 (P < 0.001) with a success rate of 62%
      (95% CI, 56%-68%) using Criteria A and 22% (95% CI, 16%-29%) using Criteria B.
      Failure risk factors using Criteria A included primary OAG (HR 3.14, P < 0.01,
      95% CI, 1.91-5.17) and past argon laser trabeculoplasty (HR 1.81, P < 0.01, 95%
      CI, 1.18-2.77). Using Criteria B, the HR for pseudoexfoliative glaucoma was 0.43
      (P < 0.01, 95% CI 0.27-0.67). Of the cases, 66 (26.8%) required subsequent
      surgery on an average of 10 months (2 days to 3.2 years) after ab interno
      trabeculotomy. CONCLUSIONS: For criteria involving IOP <=18 mm Hg, the 24-month
      survival of ab interno trabeculotomy is low. This surgery is appropriate for
      patients requiring a target IOP of 21 mm Hg or above.

PMID- 23954210
TI  - A comparison of treatment approaches for bilateral congenital nasolacrimal duct
      obstruction.
AB  - PURPOSE: To compare the clinical outcomes of two treatment approaches for
      bilateral nasolacrimal duct obstruction (NLDO) in infancy. DESIGN: Multicenter,
      randomized clinical trial. METHODS: We studied 57 infants between the ages of 6
      and <10 months who had bilateral NLDO. Participants were randomized to receive
      either (1) immediate office-based probing within two weeks (n = 31) or (2) 6
      months of observation and nonsurgical management followed by surgical facility
      based probing for unresolved cases (n = 26). Treatment success was defined as the
      absence of clinical signs of NLDO (epiphora, increased tear lake, mucous
      discharge) in both eyes on masked examination at 18 months of age. RESULTS: In
      the observation and deferred facility probing group, resolution without surgery
      occurred by 6 months after randomization in both eyes for 14 participants (56%),
      in one eye for 5 (20%), and in neither eye for 6 (24%). Eight participants in the
      observation and deferred facility probing group underwent facility probing (one
      of whom later had a second facility probing). Four participants in the immediate
      office probing group later underwent an additional procedure in a surgical
      facility. In the immediate office probing group, treatment success at 18 months
      of age occurred in both eyes for 19 of 29 (66%) participants and in one eye for 3
      (10%); in the observation and deferred facility probing group, treatment success
      occurred in both eyes for 19 of 25 (76%) participants and in one eye for 3 (12%)
      (difference in success = -10%; 95% CI = -35% to 14%). CONCLUSIONS: Both the
      immediate office probing approach and the observation and deferred facility
      probing approach are successful and reasonable treatment options for infants with
      bilateral NLDO.

PMID- 23954211
TI  - Role of hepsin in factor VII activation in zebrafish.
AB  - Factor VII, the initiator of the extrinsic coagulation cascade, circulates in
      human plasma mainly in its zymogen form, factor VII and in small amounts in its
      activated form, factor VIIa. However, the mechanism of initial generation of
      factor VIIa is not known despite intensive research using currently available
      model systems. Earlier findings suggested serine proteases factor VII activating
      protease and hepsin play a role in activating factor VII, however, it has
      remained controversial. In this paper we estimated the levels of factor VIIa and
      factor VII for the first time in zebrafish adult population and also reevaluated
      the role of the above two serine proteases in activating factor VII in vivo using
      zebrafish as a model system. Knockdown of factor VII activating protease and
      hepsin was performed followed by assaying for their effect on factor VIIa
      concentration and extrinsic coagulation as measured by the kinetic prothrombin
      time. Factor VII activating protease knockdown showed no change in kinetic
      prothrombin time and no effect on factor VIIa levels while hepsin knockdown
      increased the kinetic prothrombin time and significantly reduced the factor VIIa
      plasma levels. Our results thus indicate that hepsin plays a physiologically
      important role in factor VII activation and hemostasis in zebrafish. 

PMID- 23954212
TI  - Association between urinary levels of bisphenol-A and estrogen metabolism in
      Korean adults.
AB  - Bisphenol-A (BPA) possesses estrogenic properties both in vitro and in vivo as an
      endocrine disrupting chemical. Humans experience a long-term and cumulative
      exposure to BPA. BPA was detectable in 97.3% of 1904 urine specimens from Korean
      adults. We investigated urinary estrogen concentrations in subjects with low and
      high BPA concentrations and its possible association with estrogen metabolism.
      Urine samples were collected from a high BPA concentration group (BPA-H; n=100,
      11.05 +/- 20.47 MUg/g creatinine) and a low BPA concentration group (BPA-L;
      n=100, 0.70 +/- 0.22 MUg/g creatinine) from Korea Biomonitoring Program of
      Hazardous Materials Survey 2009-2010. Urinary estrogens were enzymatically
      hydrolyzed, extracted, and then derivatized for quantitative analysis by gas
      chromatography-mass spectrometry. Estrogen levels were higher in the BPA-H group
      than in the BPA-L group. Concentrations of estrone, 17beta-estradiol, and their
      hydroxylated metabolites in both men and women were significantly higher in the
      BPA-H group than in the BPA-L group (p<0.04). Furthermore, in the BPA-H group,
      estrogen metabolism to 4-hydroxy-estrone and 4-hydroxy-17beta-estradiol was more
      active than that to 2-hydroxy-estrone and 2-hydroxy-17beta-estradiol. Although
      single measurement and/or single spot urine samples limit the measurement of long
      term exposure to BPA, we found significant differences of estrogen metabolism in
      the BPA-H and the BPA-L groups. The increase of hydroxyestrogens, especially 4
      hydroxyestrogens, can be an important factor resulting negative effects of
      prolonged exposure to BPA.

PMID- 23954213
TI  - Occurrence and exposure assessment of polychlorinated biphenyls and
      organochlorine pesticides from homemade baby food in Korea.
AB  - Data on the residue levels of persistent organic pollutants (POPs) in baby food
      samples are scarce. This is the first study to explore current contamination
      status and exposure assessment of organochlorines (OCs), including
      polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs), in baby
      food from Korea. In this study, the concentrations of OCs were determined in
      homemade baby food samples (n=100) collected from 6-, 9-, 12- and 15-month-old
      infant groups. The average concentrations of PCBs, dichloro-diphenyl
      trichloroethanes (DDTs), hexachlorocyclohexanes (HCHs) and chlordanes (CHLs) in
      baby food samples were 37.5, 96.6, 26.0, and 13.2 pg/g fresh weight,
      respectively. The major compounds were CBs 28, 153, 52, and 33 for PCBs and p,p'
      DDE, p,p'-DDT and beta-HCH for OCPs. The contribution of DDTs to the total OC
      concentrations increased from 30% (6-month-old infants) to 67% (15-month-old
      infants) with increasing infant age, while the concentrations of PCBs, HCHs and
      CHLs gradually decreased with increasing infant age, suggesting that highest
      priority for risk reduction of DDTs. The estimated daily intakes (EDIs) of OCs in
      Korean infants from baby food consumption were lower than the thresholds proposed
      by the United States Environmental Protection Agency and Health Canada, implying
      limited potential health risks. However, considering simultaneous exposure from
      baby food and breast milk consumption, chlordanes and heptachlor epoxide posed
      potential health risks. Considering the importance of early development and the
      vulnerability of infants, it is essential to perform systematic monitoring and
      management programs of OCs in baby food for risk reduction in Korean infants.

PMID- 23954214
TI  - Efficacy of vitamin D in treating multiple sclerosis-like neuroinflammation
      depends on developmental stage.
AB  - The association of vitamin D deficiency with higher prevalence, relapse rate and
      progression of multiple sclerosis (MS) has stimulated great interest in using
      vitamin D supplementation as a preventative measure and even a therapy for
      established MS. However, there is a considerable lack of evidence when it comes
      to an age/developmental stage-dependent efficacy of vitamin D action and a time
      window for the most effective prophylactic treatment remains unclear. We studied
      the effect of vitamin D supplementation in myelin oligodendrocyte glycoprotein
      (MOG)-induced experimental autoimmune encephalomyelitis (EAE), an animal model of
      MS, at three different developmental stages in rats. Supplementation treatment
      was initiated: i) prior to gestation and maintained throughout pre- and early
      postnatal development (gestation and lactation); ii) after weaning, throughout
      juvenile/adolescence period and iii) in adult age. We observed a marked
      attenuation of EAE in juvenile/adolescent rats reflected in a less severe CNS
      inflammation and demyelination, accompanied by a lower amount of IFN-gamma
      producing MOG-specific T cells. Moreover, the cytokine expression pattern in
      these rats reflected a more anti-inflammatory phenotype of their peripheral
      immune response. However, the same supplementation regimen failed to improve the
      disease outcome both in adult rats and in rats treated during pre- and early post
      natal development. Our data demonstrate a developmental stage-dependent
      efficiency of vitamin D to ameliorate neuroinflammation, suggesting that
      childhood and adolescence should be the target for the most effective preventive
      treatment.

PMID- 23954215
TI  - Phrenic motoneuron discharge patterns following chronic cervical spinal cord
      injury.
AB  - Cervical spinal cord injury (SCI) dramatically disrupts synaptic inputs and
      triggers biochemical, as well as morphological, plasticity in relation to the
      phrenic motor neuron (PhMN) pool. Accordingly, our primary purpose was to
      determine if chronic SCI induces fundamental changes in the recruitment profile
      and discharge patterns of PhMNs. Individual PhMN action potentials were recorded
      from the phrenic nerve ipsilateral to lateral cervical (C2) hemisection injury
      (C2Hx) in anesthetized adult male rats at 2, 4 or 8 wks post-injury and in
      uninjured controls. PhMNs were phenotypically classified as early (Early-I) or
      late inspiratory (Late-I), or silent according to discharge patterns. Following
      C2Hx, the distribution of PhMNs was dominated by Late-I and silent cells. Late-I
      burst parameters (e.g., spikes per breath, burst frequency and duration) were
      initially reduced but returned towards control values by 8wks post-injury. In
      addition, a unique PhMN burst pattern emerged after C2Hx in which Early-I cells
      burst tonically during hypocapnic inspiratory apnea. We also quantified the
      impact of gradual reductions in end-tidal CO2 partial pressure (PETCO2) on
      bilateral phrenic nerve activity. Compared to control rats, as PETCO2 declined,
      the C2Hx animals had greater inspiratory frequencies (breaths*min(-1)) and more
      substantial decreases in ipsilateral phrenic burst amplitude. We conclude that
      the primary physiological impact of C2Hx on ipsilateral PhMN burst patterns is a
      persistent delay in burst onset, transient reductions in burst frequency, and the
      emergence of tonic burst patterns. The inspiratory frequency data suggest that
      plasticity in brainstem networks is likely to play an important role in phrenic
      motor output after cervical SCI.

PMID- 23954216
TI  - An unusual case of pleuropericardial neutrophilic effusion associated with
      valproate.

PMID- 23954217
TI  - Evaluation of the Roche prototype 454 HIV-1 ultradeep sequencing drug resistance
      assay in a routine diagnostic laboratory.
AB  - BACKGROUND: Studies have shown that low-frequency resistance mutations can
      influence treatment outcome. However, the lack of a standardized high-throughput
      assay has precluded their detection in clinical settings. OBJECTIVE: To evaluate
      the performance of the Roche prototype 454 UDS HIV-1 drug resistance assay (UDS
      assay) in a routine diagnostic laboratory. STUDY DESIGN: 50 plasma samples,
      previously characterized by population sequencing and that had shown >=1
      resistance associated mutation (RAM), were retrospectively tested by the UDS
      assay, including 18 B and 32 non-B subtypes; viral loads between 114-1,806,407
      cp/ml; drug-naive (n=27) and drug-experienced (n=23) individuals. RESULTS: The
      UDS assay was successful for 37/50 (74%) samples. It detected all RAMs found by
      population sequencing at frequencies above 20%. In addition, 39 low-frequency
      RAMs were exclusively detected by the UDS assay at frequencies below 20% in both
      drug-naive (19/26, 73%) and drug-experienced (9/18, 50%) individuals. UDS results
      would lead to changes from susceptible to resistant to efavirenz (EFV) in one
      drug-naive individual with suboptimal response to an EFV-containing regimen and
      from susceptible to resistance to lamivudine (3TC) in one drug naive subject who
      subsequently failed a 3TC-containing regimen and in a treatment experienced
      subject who had failed a 3TC-containing regimen. CONCLUSIONS: The UDS assay
      performed well across a wide range of subtypes and viral loads; it showed perfect
      agreement with population sequencing for all RAMs analyzed. In addition, the UDS
      assay detected additional mutations at frequencies below 20% which correlate with
      patients' treatment history and had in some cases important prognostic
      implications.

PMID- 23954218
TI  - Consumption of fried foods and risk of metabolic syndrome: the SUN cohort study.
AB  - BACKGROUND & AIMS: There is scarce evidence from long-term prospective studies
      relating the consumption of fried foods with the incidence of Metabolic Syndrome
      (MS). The aim of this study was to assess the association between fried food
      consumption and the incidence of MS. METHODS: We followed 8289 participants (2813
      men and 5476 women, mean age = 35.9 y, SD = 10.4) during a median period of 8.3
      y. They were initially free of any MS criteria. MS was defined according to the
      American Heart Association and the International Diabetes Federation criteria as
      outlined in the harmonized definition for MS. Each component of the MS was
      assessed at the 6th and 8th-y of follow-up. The outcome was defined as the
      presence of >=3 of the components of MS after >=6 years of follow-up. RESULTS:
      During 65335 person-years, 420 incident cases of MS were identified. Frequent
      consumption of fried foods was not associated with the incidence of MS [HR = 0.98
      (95% CI: 0.77-1.26) p for trend = 0.862]. However, two components of the MS,
      central adiposity and high blood pressure were positively associated with fried
      food consumption [HR for consumption >4 times/week compared with <=2 times/week =
      1.10 (95% CI: 1.01-1.19) (p for trend 0.022) and HR = 1.16 (95% CI: 1.02-1.32) (p
      for trend 0.011), respectively] after multivariable adjustment. CONCLUSIONS: In
      this Mediterranean cohort of relatively young adults, frequent consumption of
      fried foods was not associated with MS. Two out of five components of MS (central
      adiposity and high blood pressure) were positively associated with frequent fried
      food consumption.

PMID- 23954219
TI  - Association between resistin +299A/A genotype and nonalcoholic fatty liver
      disease in Chinese patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: To investigate the relationship between the resistin intronic +299G/A
      polymorphism and nonalcoholic fatty liver disease (NAFLD) in patients with type 2
      diabetes mellitus (T2DM). METHODS: We selected 738 T2DM patients, including 395
      with NAFLD and 343 without fatty liver disease, as well as 279 healthy control
      individuals, and analyzed their resistin +299G/A polymorphism genotype by
      polymerase chain reaction-restriction fragment length polymorphism. RESULTS:
      Plasma resistin levels in T2DM patients with NAFLD were at the highest (P<0.05).
      The frequency of AA genotype at the +299 site of the resistin gene in patients
      with concurrent T2DM combined with NAFLD was significantly different from that in
      the control (P<0.05). The AA genotype was found to be associated with a 1.80-fold
      increased risk for T2DM combined with NAFLD, 2.05-fold increased risk for obesity
      and 2.37-fold increased risk for obesity of abdominal type compared to the GG
      (P<0.05, respectively). The multivariate non-conditional logistic regression
      model analysis further shows that the AA genotype is a risk factor for the
      development of NAFLD in T2DM patients (OR, 2.32; 95% CI, 1.05-4.68; P<0.05).
      CONCLUSION: The resistin +299AA genotype may be associated with increases in the
      risk of the NAFLD development in T2DM patients.

PMID- 23954220
TI  - Combined effects of four SNPs within goat PRLR gene on milk production traits.
AB  - Xinong Saanen (SN, n=323) and Guanzhong (GZ, n=197) goat breeds were used to
      detect single nucleotide polymorphisms (SNPs) in the coding regions with their
      intron-exon boundaries of prolactin receptor (PRLR) gene by DNA sequencing,
      primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) and
      PCR-restriction fragment length polymorphism (PCR-RFLP). Four novel SNPs
      (g.40452T>C, g.40471G>A, g.61677G>A and g.61865G>A) were identified. The
      g.61677G>A and g.61865G>A SNPs caused amino acid variations p.Ser485Asn and
      p.Val548Met, respectively. Both g.40452T>C and g.40471G>A loci were closely
      linked in SN and GZ goat breeds (r(2)>0.33). In addition, there was also a close
      linkage between g.61677G>A and g.61865G>A loci in both goat breeds. Statistical
      results indicated that the g.40452T>C, g.61677G>A and g.61865G>A SNPs were
      significantly associated with milk production traits in SN and GZ breeds. Further
      analysis revealed that combinative genotype C1 (TTAAGGGG) was better than the
      others for milk yield in SN and GZ goat breeds. These results are consistent with
      the regulatory function of PRLR in mammary gland development, milk secretion, and
      expression of milk protein genes, and extend the spectrum of genetic variation of
      the caprine PRLR gene, which might contribute to goat genetic resources and
      breeding. 

PMID- 23954221
TI  - Prognostic value of epidermal growth factor receptor in patients with gastric
      cancer: a meta-analysis.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) plays important roles in
      the development of gastric cancer. This study aims to analyze the prognostic
      value of EGFR in patients with gastric cancer. METHODS: A meta-analysis is
      performed by searching Cochrane Library, PubMed, EMBASE and Science Direct
      databases from Jan 1970 to May 2013. Data are extracted from studies evaluating
      the survival of gastric cancer patients with either positive or negative EGFR
      expression. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) are
      calculated. RESULTS: Totally 1600 cases of gastric cancer patients from five
      studies are subjected to final analysis. The HR of post-operational survival of
      patients with positive EGFR expression is 1.16 (95% CI: 0.94-1.43) as compared
      with those with negative expression, indicating that positive EGFR expression
      does not significantly predict the poor survival of gastric cancer. CONCLUSIONS:
      EGFR expression is not an independent predictor for the survival of gastric
      cancer patients.

PMID- 23954222
TI  - Analysis of three leafminers' complete mitochondrial genomes.
AB  - Liriomyza trifolii (Burgess), Liriomyza huidobrensis (Blanchard), and Liriomyza
      bryoniae (Kaltenbach), are three closely related and economically important
      leafminer pests in the world. This study examined the complete mitochondrial
      genomes of L. trifolii, L. huidobrensis and L. bryoniae, which were 16,141 bp,
      16,236 bp and 16,183 bp in length, respectively. All of them displayed 37 typical
      animal mitochondrial genes and an A+T-rich region. The genomes were highly
      compact with only 60-68 bp of non-coding intergenic spacer. However, considerable
      differences in the A+T-rich region were detected among the three species. Results
      of this study also showed the two ribosomal RNA genes of the three species had
      very limited variable sites and thus should not provide much information in the
      study of population genetics of these species. Data generated from three
      leafminers' complete mitochondrial genomes should provide valuable information in
      studying phylogeny of Diptera, and developing genetic markers for species
      identification in leafminers.

PMID- 23954223
TI  - WITHDRAWN: Marfan syndrome: An eyesight of syndrome.
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- 23954224
TI  - First functional analysis of a novel splicing mutation in the B3GALTL gene by an
      ex vivo approach in Tunisian patients with typical Peters plus syndrome.
AB  - Peters plus syndrome is a rare recessive autosomal disorder comprising ocular
      anterior segment dysgenesis, short stature, hand abnormalities and distinctive
      facial features. It was related only to mutations in the B3GALTL gene in the
      13q12.3 region. In this study, we undertook the first functional analysis of a
      novel c.597-2 A>G splicing mutation within the B3GALTL gene using an ex-vivo
      approach. The results showed a complete skipping of exon 8 in the B3GALTL cDNA,
      which altered the open reading frame of the mutant transcript and generated a PTC
      within exon 9. This finding potentially elicits the nonsense mRNA to degradation
      by NMD (nonsense-mediated mRNA decay). The theoretical consequences of splice
      site mutations, predicted with the bioinformatics tool Human Splice Finder, were
      investigated and evaluated in relation to ex-vivo results. The findings confirmed
      the key role played by the B3GALTL gene in typical Peters-plus syndromes and the
      utility of mRNA analysis to understand the primary impacts of this mutation and
      the phenotype of the disease. 

PMID- 23954226
TI  - Sizeable acquired subglottic cyst in a baby with Williams-Beuren syndrome:
      association or coincidence?
AB  - We describe a case of an acquired subglottic cyst presented with persistent
      stridor and voice hoarsening in a baby diagnosed with Williams-Beuren syndrome
      that was born premature and required intubation during neonatal period. We also
      comment on whether this is a coincidence or there can be an association between
      impaired elastogenesis, a feature of patients with the syndrome and the formation
      of a subglottic cyst. 

PMID- 23954225
TI  - Genetic polymorphisms of pharmacogenomic VIP variants in the Kyrgyz population
      from northwest China.
AB  - Pharmacogenomic variant information is well known for major human populations;
      however, this information is less commonly studied in minorities. In the present
      study, we genotyped 85 very important pharmacogenetic (VIP) variants (selected
      from the PharmGKB database) in the Kyrgyz population and compared our data with
      other four major human populations including Han Chinese in Beijing, China (CHB),
      the Japanese in Tokyo, Japan (JPT), a northern and western Europe population
      (CEU), and the Yoruba in Ibadan, Nigeria (YRI). There were 13, 12 and 16 of the
      selected VIP variant genotype frequencies in the Kyrgyz which differed from those
      of the CHB, JPT and CEU, respectively (p<0.005). In the YRI, there were 32
      different variants, compared to the Kyrgyz (p<0.005). Genotype frequencies of
      ADH1B, AHR, CYP3A5, PTGS2, VDR, and VKORC1 in the Kyrgyz differed widely from
      those in the four populations. Haplotype analyses also showed differences among
      the Kyrgyz and the other four populations. Our results complement the information
      provided by the database of pharmacogenomics on Kyrgyz. We provide a theoretical
      basis for safer drug administration and individualized treatment plans for the
      Kyrgyz. We also provide a template for the study of pharmacogenomics in various
      ethnic minority groups in China. 

PMID- 23954227
TI  - Novel and recurrent mutations in the TAT gene in Tunisian families affected with
      Richner-Hanhart syndrome.
AB  - Tyrosinemia type II, also designated as oculocutaneous tyrosinemia or Richner
      Hanhart syndrome (RHS), is a very rare autosomal recessive disorder. In the
      present study, we report clinical features and molecular genetic investigation of
      the tyrosine aminotransferase (TAT) gene in two young patients, both born to
      consanguineous unions between first-degree cousins. These two unrelated families
      originated from Northern and Southern Tunisia. The clinical diagnosis was based
      on the observation of several complications related to Richner-Hanhart syndrome:
      recurrent eye redness, tearing and burning pain, photophobia, bilateral
      pseudodendritic keratitis, an erythematous and painful focal palmo-plantar
      hyperkeratosis and a mild delay of mental development. The diagnosis was
      confirmed by biochemical analysis. Sequencing of the TAT gene revealed the
      presence of a previously reported missense mutation (c.452G>A, p.Cys151Tyr) in a
      Tunisian family, and a novel G duplication (c.869dupG, p.Trp291Leufs 6). Early
      diagnosis of RHS and protein-restricted diet are crucial to reduce the risk and
      the severity of long-term complications of hypertyrosinemia such as intellectual
      disability.

PMID- 23954228
TI  - DAX1 regulatory networks unveil conserved and potentially new functions.
AB  - DAX1 is an orphan nuclear receptor with actions in mammalian sex determination,
      regulation of steroidogenesis, embryonic development and neural differentiation.
      Conserved patterns of DAX1 gene expression from mammals to fish have been taken
      to suggest conserved function. In the present study, the European sea bass,
      Dicentrarchus labrax, DAX1 promoter was isolated and its conserved features
      compared to other fish and mammalian DAX1 promoters in order to derive common
      regulators and functional gene networks. Fish and mammalian DAX1 promoters share
      common sets of transcription factor frameworks which were also present in the
      promoter region of another 127 genes. Pathway analysis clustered these into
      candidate gene networks associated with the fish and mammalian DAX1. The networks
      identified are concordant with described functions for DAX1 in embryogenesis,
      regulation of transcription, endocrine development and steroid production. Novel
      candidate gene network partners were also identified, which implicate DAX1 in ion
      homeostasis and transport, lipid transport and skeletal development. Experimental
      evidence is provided supporting roles for DAX1 in steroid signalling and
      osmoregulation in fish. These results highlight the usefulness of the in silico
      comparative approach to analyse gene regulation for hypothesis generation.
      Conserved promoter architecture can be used also to predict potentially new gene
      functions. The approach reported can be applied to genes from model and non-model
      species.

PMID- 23954231
TI  - Hemojuvelin-hepcidin axis modeled and analyzed using Petri nets.
AB  - Systems biology approach to investigate biological phenomena seems to be very
      promising because it is capable to capture one of the fundamental properties of
      living organisms, i.e. their inherent complexity. It allows for analysis
      biological entities as complex systems of interacting objects. The first and
      necessary step of such an analysis is building a precise model of the studied
      biological system. This model is expressed in the language of some branch of
      mathematics, as for example, differential equations. During the last two decades
      the theory of Petri nets has appeared to be very well suited for building models
      of biological systems. The structure of these nets reflects the structure of
      interacting biological molecules and processes. Moreover, on one hand, Petri nets
      have intuitive graphical representation being very helpful in understanding the
      structure of the system and on the other hand, there is a lot of mathematical
      methods and software tools supporting an analysis of the properties of the nets.
      In this paper a Petri net based model of the hemojuvelin-hepcidin axis involved
      in the maintenance of the human body iron homeostasis is presented. The analysis
      based mainly on T-invariants of the model properties has been made and some
      biological conclusions have been drawn. 

PMID- 23954230
TI  - Association of leptin receptor gene Q223R polymorphism on lipid profiles in
      comparison study between obese and non-obese subjects.
AB  - OBJECTIVES: Leptin is a hormone secreted from adipocytes. It regulates metabolism
      and energy homeostasis through the leptin receptor (LEPR) which is localized
      centrally in hypothalamus as well as in peripheral tissues. The aim of this study
      was to investigate the association of leptin receptor gene Q223R polymorphism on
      obesity in association with body mass index (BMI), lipid parameters, plasma
      leptin levels and homeostasis model assessment of insulin resistance (HOMA-IR).
      DESIGN AND METHODS: The study included 110 obese and 90 non-obese subjects. The
      LEPR Q223R polymorphism was determined by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). Plasma leptin levels, serum lipid and
      antropometric parameters were measured. RESULTS: No association was found between
      LEPR gene Q223R polymorphism and BMI in both study and control groups. Strikingly
      study group with non-obese subjects and with the RR genotype (homozygous mutant)
      had significantly higher serum total cholesterol (p<0.001) and low density
      lipoprotein cholesterol (LDL-cholesterol) levels (p<0.05) than QR (heterozygous)
      and QQ (wild type) genotypes. In obese group, subjects with the RR genotypes had
      significantly higher triglycerides (p<0.05) levels, waist (p<0.05) and hip
      circumferences (p<0.001) than the QQ and QR genotypes. CONCLUSIONS: Our results
      suggest that the LEPR gene Q223R polymorphism has an association with waist and
      hip circumferences in obese group but no direct association with obesity although
      there is a significant influence on lipid profile both in obese and non-obese
      subjects.

PMID- 23954232
TI  - Impaired memory and reduced sensitivity to the circadian period lengthening
      effects of methamphetamine in mice selected for high methamphetamine consumption.
AB  - Drug abuse runs in families suggesting the involvement of genetic risk factors.
      Differences in addiction-related neurobiological systems, including learning and
      memory and circadian rhythms, may exist prior to developing addiction. We
      characterized the cognitive phenotypes and the free-running circadian period of
      mouse lines selectively bred for high methamphetamine (MA) drinking (MA high
      drinking or MAHDR) and low MA drinking (MA low drinking or MALDR). MA-naive MALDR
      mice showed spatial memory retention while MAHDR mice did not. MA-naive MAHDR
      mice had elevated hippocampal levels of the AMPA receptor subunits GluA2 (old
      terminology: GluR2), but not GluA1 (old terminology: GluR1). There were no line
      differences in the free running period (tau) when only water was available.
      During a 25 mg/L MA solution access period (vs water), there was an increase in
      tau in MALDR but not MAHDR mice, although MAHDR mice consumed significantly more
      MA. During a 50 mg/L MA solution access period (vs water), both lines showed an
      increased tau. There was a positive correlation between MA consumption and tau
      from baseline in MALDR, but not MAHDR, mice. Thus, a heritable proclivity for
      elevated MA self-administration may be associated with impairments in hippocampus
      dependent memory and reduced sensitivity to effects of MA on lengthening of the
      circadian period.

PMID- 23954233
TI  - Cysteine mutations cause defective tyrosine phosphorylation in MEGF10 myopathy.
AB  - Recessive mutations in MEGF10 are known to cause a congenital myopathy in humans.
      Two mutations in the extracellular EGF-like domains of MEGF10, C326R and C774R,
      were associated with decreased tyrosine phosphorylation of MEGF10 in vitro. Y1030
      was identified to be the major tyrosine phosphorylation site in MEGF10 and is
      phosphorylated at least in part by c-Src. Overexpression of wild-type MEGF10
      enhanced C2C12 myoblast proliferation, while overexpression of Y1030F mutated
      MEGF10 did not. We conclude that MEGF10-mediated signaling via tyrosine
      phosphorylation helps to regulate myoblast proliferation. Defects in this
      signaling pathway may contribute to the disease mechanism of MEGF10 myopathy. 

PMID- 23954235
TI  - The role of the upper sample size limit in two-stage bioequivalence designs.
AB  - Two-stage designs (TSDs) are currently recommended by the regulatory authorities
      for bioequivalence (BE) assessment. The TSDs presented until now rely on an
      assumed geometric mean ratio (GMR) value of the BE metric in stage I in order to
      avoid inflation of type I error. In contrast, this work proposes a more realistic
      TSD design where sample re-estimation relies not only on the variability of stage
      I, but also on the observed GMR. In these cases, an upper sample size limit (UL)
      is introduced in order to prevent inflation of type I error. The aim of this
      study is to unveil the impact of UL on two TSD bioequivalence approaches which
      are based entirely on the interim results. Monte Carlo simulations were used to
      investigate several different scenarios of UL levels, within-subject variability,
      different starting number of subjects, and GMR. The use of UL leads to no
      inflation of type I error. As UL values increase, the % probability of declaring
      BE becomes higher. The starting sample size and the variability of the study
      affect type I error. Increased UL levels result in higher total sample sizes of
      the TSD which are more pronounced for highly variable drugs. 

PMID- 23954229
TI  - Kinesin-5: cross-bridging mechanism to targeted clinical therapy.
AB  - Kinesin motor proteins comprise an ATPase superfamily that works hand in hand
      with microtubules in every eukaryote. The mitotic kinesins, by virtue of their
      potential therapeutic role in cancerous cells, have been a major focus of
      research for the past 28 years since the discovery of the canonical Kinesin-1
      heavy chain. Perhaps the simplest player in mitotic spindle assembly, Kinesin-5
      (also known as Kif11, Eg5, or kinesin spindle protein, KSP) is a plus-end
      directed motor localized to interpolar spindle microtubules and to the spindle
      poles. Comprised of a homotetramer complex, its function primarily is to slide
      anti-parallel microtubules apart from one another. Based on multi-faceted
      analyses of this motor from numerous laboratories over the years, we have learned
      a great deal about the function of this motor at the atomic level for catalysis
      and as an integrated element of the cytoskeleton. These data have, in turn,
      informed the function of motile kinesins on the whole, as well as spearheaded
      integrative models of the mitotic apparatus in particular and regulation of the
      microtubule cytoskeleton in general. We review what is known about how this
      nanomotor works, its place inside the cytoskeleton of cells, and its small
      molecule inhibitors that provide a toolbox for understanding motor function and
      for anticancer treatment in the clinic.

PMID- 23954234
TI  - Protoporphyrin IX accumulation disrupts mitochondrial dynamics and function in
      ABCG2-deficient hepatocytes.
AB  - Targeted inhibition of multidrug ABCG2 transporter is believed to improve cancer
      therapeutics. However, the consequences of ABCG2 inhibition have not been
      systematically evaluated since ABCG2 is expressed in several organs including the
      liver. Here, we demonstrate that ABCG2-deficient hepatocytes have increased
      amounts of fragmental mitochondria accompanied by disruption of mitochondrial
      dynamics and functions. This disruption was due to ABCG2 knockout elevating
      intracellular protoporphyrin IX, which led to upregulation of DRP-1-mediated
      mitochondrial fission. The finding that ABCG2 deficiency can generate
      dysfunctional mitochondria in hepatocytes raises concerns regarding the
      systematic use of ABCG2 inhibitor in cancer patients. 

PMID- 23954236
TI  - In vivo evaluation of chondroitin sulfate-glycyl-prednisolone for anti-arthritic
      effectiveness and pharmacokinetic characteristics.
AB  - A conjugate between chondroitin sulfate (CS) and glycyl-prednisolone (GP), named
      CS-GP, was prepared as a delivery system for the treatment of rheumatoid
      arthritis by referring to the previous report. CS-GP conjugates with different
      prednisolone (PD) contents of 1.4, 2.0 and 4.3% (w/w) were obtained, and their
      conversion characteristics were investigated at 37  degrees C under pH 6 and 7.4.
      Release profiles were similar among the conjugates, being slow at pH 6 (24 h: 9
      14%), and fairly fast at pH 7.4 (7 h: 46-58%). CS-GP, PD, CS and the PD/CS
      mixture were investigated for anti-inflammatory effects by i.v. administration to
      rats with adjuvant-induced arthritis. At 2.5mg PD equiv./kg*2 d, CS-GP
      significantly suppressed swelling of both hind paws, while other preparations
      were less effective. CS-GP (2.5mg PD equiv./kg*2 d) tended to be more effective
      than PD (5 mg/kg*2 d). Change in body weight indicated that CS-GP was not toxic.
      After i.v. injection in normal rats, CS-GP showed much higher plasma levels than
      PD alone, and organ accumulation of CS-GP was not observed. CS-GP was suggested
      to be possibly useful for the treatment of rheumatoid arthritis.

PMID- 23954237
TI  - Novel cyclodextrin nanosponges for delivery of calcium in hyperphosphatemia.
AB  - Cyclodextrin nanosponges are solid, porous nanoparticulate three dimensional
      structures, have been used as delivery system of different drugs. In this work,
      new cyclodextrin-based nanosponges of calcium carbonate were prepared by polymer
      condensation method to release the calcium in controlled manner in the treatment
      of hyperphosphatemia as novel carriers. SEM measurements revealed their roughly
      spherical shape, porous nature and mean particle size of about 400 nm. Zeta
      potentials of the nanosponges were sufficiently high to obtain stable
      formulations. The encapsulation efficiencies of calcium in nanosponge
      formulations were found to be 81-95%. The moisture contents of the nanosponges
      were in the range of 0.1-0.7%. The optimized formulation produces enteric and
      controlled release kinetics of calcium in the management and treatment of
      hyperphosphatemia. It was also observed that calcium ions bound efficiently to
      free phosphate in a pH-dependent fashion especially at pH 7. In accelerated
      stability study no significant changes occurred in physical appearance, size and
      nature of drug in formulation for 3 months. The results of FTIR and DSC confirmed
      that calcium carbonate was encapsulated in nanosponges structure.

PMID- 23954238
TI  - 3-Carboxy-pyrazolinalanine as a new scaffold for developing potent and selective
      NMDA receptor antagonists.
AB  - A synthetic method for the preparation of suitably protected 3-carboxy-Delta2
      pyrazolin-5-yl-alanine was developed. This scaffold is amenable to further
      decoration at the N1 position and was used to generate novel NMDA receptor
      ligands. Although weaker than the previously reported N1-Ph derivatives, the new
      ligands retain the ability to selectively bind to NMDA receptor with micromolar
      to submicromolar affinity. Considering the relevance of the N-functionalization
      for the biological activity, the results presented in this communication are
      preliminary to a full SAR study of this novel class of NMDA receptor antagonists.

PMID- 23954239
TI  - Hybrid benzofuran-bisindole derivatives: new prototypes with promising anti
      hyperlipidemic activities.
AB  - A series of different benzofuran-bisindole hybrids were synthesized and evaluated
      in vitro for their antioxidant and in vivo for antidyslipidemic activity in
      triton WR-1339 induced hyperlipidemic rats. Among the series, compounds 4a, 4c,
      4h and 4j showed significant decrease in plasma levels of total cholesterol (TC),
      phospholipids (PL) and triglycerides (TG) followed by increase in post heparin
      lipolytic activity (PHLA). In addition, the active hybrids possessed moderate
      antioxidant properties and increased the plasma lecithin cholesterol
      acyltransferase (LCAT) activity, which plays a key role in lipoprotein metabolism
      contributing to an increased level of HDL-C in serum. These results indicate that
      these hybrids constitute novel prototypes for the management of dyslipidemia. 

PMID- 23954240
TI  - Comparative study of microtubule inhibitors--estramustine and natural
      podophyllotoxin conjugated PAMAM dendrimer on glioma cell proliferation.
AB  - The synthetic estramustine (EM) and natural podophyllotoxin (PODO) anti-mitotic
      agents that inhibit tubulin polymerization are known anticancer agents. As low
      bioavailability limits their anticancer properties, we investigated whether
      conjugation with PAMAM dendrimer (D) could enhance the activity of D-EM and D
      PODO by altering their release pattern. Release kinetics indicated synthesized
      conjugates to be stable against hydrolytic cleavage and showed sustained release
      characteristics. However, release of D-EM was slow compared to D-PODO conjugate.
      Antitumor effect of these conjugates on glioma cells revealed (i) increased cell
      death and cell cycle arrest (ii) decreased migration and (iii) increased tubulin
      depolymerization as compared to free drug. Importantly, the effects of natural
      PODO conjugate on glioma cell survival and migration is more pronounced than D
      EM. 

PMID- 23954242
TI  - Enricher reactor--permeable reactive biobarrier approach for removing a mixture
      of contaminants with substrate interactions.
AB  - A laboratory-scale enricher reactor (ER) - permeable reactive biobarrier (PRBB)
      system was studied to address performance loss of a PRBB due to substrate
      interactions among a mixture of benzene, toluene, ethylbenzene, and xylene (BTEX)
      in groundwater, when the mixture reappeared after a 10-day absence period.
      Toluene and BTEX as an inducer in ER were compared to investigate toluene as a
      potential single inducer in ER. PRBBs without ER augmentation experienced
      performance losses ranging from 11% to 35% for PRBBs initially inoculated with
      toluene degraders and 22% to 33% for PRBBs initially inoculated with BTEX
      degraders. Bacterial communities changed substantially in these PRBBs after the
      absence period, which could contribute to the performance losses. PRBBs augmented
      with toluene degraders overcame the inhibition interaction between benzene and
      toluene, and showed a superior removal performance for toluene degradation
      suggesting that toluene can be used as a single inducer in an ER. 

PMID- 23954241
TI  - Novel compstatin family peptides inhibit complement activation by drusen-like
      deposits in human retinal pigmented epithelial cell cultures.
AB  - We have used a novel human retinal pigmented epithelial (RPE) cell-based model
      that mimics drusen biogenesis and the pathobiology of age-related macular
      degeneration to evaluate the efficacy of newly designed peptide inhibitors of the
      complement system. The peptides belong to the compstatin family and, compared to
      existing compstatin analogs, have been optimized to promote binding to their
      target, complement protein C3, and to enhance solubility by improving their
      polarity/hydrophobicity ratios. Based on analysis of molecular dynamics
      simulation data of peptide-C3 complexes, novel binding features were designed by
      introducing intermolecular salt bridge-forming arginines at the N-terminus and at
      position -1 of N-terminal dipeptide extensions. Our study demonstrates that the
      RPE cell assay has discriminatory capability for measuring the efficacy and
      potency of inhibitory peptides in a macular disease environment. 

PMID- 23954243
TI  - Removal and factors influencing removal of sulfonamides and trimethoprim from
      domestic sewage in constructed wetlands.
AB  - Twelve pilot-scale constructed wetlands with different configurations were set up
      in the field to evaluate the removal and factors that influence removal of
      sulfonamides (sulfadiazine, sulfapyridine, sulfacetamide, sulfamethazine and
      sulfamethoxazole) and trimethoprim from domestic sewage. The treatments included
      four flow types, three substrates, two plants and three hydraulic loading rates
      across two seasons (summer and winter). Most target antibiotics were efficiently
      removed by specific constructed wetlands; in particular, all types of constructed
      wetlands performed well for the degradation of sulfapyridine. Flow types were the
      most important influencing factor in this study, and the best removal of
      sulfonamides was achieved in vertical subsurface-flow constructed wetlands;
      however, the opposite phenomenon was found with trimethoprim. Significant
      relationships were observed between antibiotic degradation and higher temperature
      and redox potential, which indicated that microbiological pathways were the most
      probable degradation route for sulfonamides and trimethoprim in constructed
      wetlands. 

PMID- 23954244
TI  - Systematic screening of carbon-based anode materials for microbial fuel cells
      with Shewanella oneidensis MR-1.
AB  - We present a systematic screening of carbon-based anode materials for microbial
      fuel cells with Shewanella oneidensis MR-1. Under anoxic conditions nanoporous
      activated carbon cloth is a superior anode material in terms of current density
      normalized to the projected anode area and anode volume (24.0+/-0.3 MUA cm(-2)
      and 482+/-7 MUA cm(-3) at -0.2 vs. SCE, respectively). The good performance can
      be attributed to the high specific surface area of the material, which is
      available for mediated electron transfer through self-secreted flavins. Under
      aerated conditions no influence of the specific surface area is observed, which
      we attribute to a shift from primary indirect electron transfer by mediators to
      direct electron transfer via adherent cells. Furthermore, we show that an aerated
      initial growth phase enhances the current density under subsequent anoxic
      conditions fivefold when compared to a similar experiment that was conducted
      under permanently anoxic conditions.

PMID- 23954245
TI  - Comparison of the enzymatic digestibility of physically and chemically pretreated
      selected line of diploid-Miscanthus sinensis Shiozuka and triploid-M.*giganteus.
AB  - The diploid Miscanthus sinensis "Shiozuka" which was selected as a high-biomass
      producing line, and the triploid M. * giganteus (M*G) were treated by ball
      milling (physical treatment) and alkaline hydrogen peroxide treatment (AHP;
      chemical treatment), and their structural sugar compositions and enzymatic
      digestibility were compared. The structural sugar content of Shiozuka was
      moderate and lower than that of M*G. The Klason lignin content of Shiozuka was
      also lower than that of M*G. However, Shiozuka was sensitive to ball milling and
      AHP treatment; ball milled and AHP-treated Shiozuka had higher enzymatic
      digestibility than ball milled and AHP-treated M*G. Shiozuka would be promising
      feedstock to obtain fermentable sugars with low energy consumption. Finally,
      enzymes for the hydrolysis of chemically treated Miscanthus were isolated from
      Trichoderma reesei ATCC 66589 and Penicillium pinophilum. The sugar yield could
      be increased by enzymatic hydrolysis of AHP-treated samples with NaOH and H2O2
      and the isolated enzymes.

PMID- 23954246
TI  - Anaerobic digestion of wheat straw--performance of continuous solid-state
      digestion.
AB  - In this study the upflow anaerobic solid-state (UASS) reactor was operated at
      various conditions to optimize the process parameters for anaerobically digesting
      wheat straw in a continuous process. Additionally, particle size effects have
      been studied in the operation at 55 and 60 degrees C. Moreover, the incremental
      effect of the organic loading rate (OLR) to the system was examined from 2.5 to 8
      gVS L(-1) d(-1). It was found that the UASS operating at 60  degrees C with a
      small OLR yields highest methane production, but the advantage over thermophilic
      operation is negligible. The rise in OLR reduces the systems yields, as expected.
      From OLR=8 gVS L(-1) d(-1) a second stage is necessary to circumvent volatile
      fatty acids accumulation.

PMID- 23954247
TI  - Linking nitrifying biofilm characteristics and nitrification performance in
      moving-bed biofilm reactors for polluted raw water pretreatment.
AB  - Biofilm physiology was characterized by four biofilm constituents, i.e.,
      polysaccharides, proteins (PN), humic-like substances and phospholipids (PL), for
      the first time to explore the relationships between biofilm characteristics and
      nitrification performance in moving-bed biofilm reactors (MBBRs) designed for
      pretreatment of polluted raw surface water for potable supply. The biofilm
      compositions depended highly on the balance of microbial decay and nitrification
      processes. The increased ammonia loading greatly regulated the community
      structure, promoting the dominance of nitrifiers and their proportions in the
      nitrifying biofilm. Nitrification rate and activity correlated linearly with the
      fractions of volatile solids (VS), PN and PL, which were related to nitrification
      processes in the biofilm. The specific biofilm activity demonstrated an
      exponential-asymptotic relationship with ratios of PN/VS and PL/VS. Thus,
      analyzing biofilm characteristics can be valid for estimating nitrification
      performance in MBBRs, and may offer engineers with basis to optimize MBBR design
      and operation. 

PMID- 23954248
TI  - When and how should magnetic resonance imaging be used in evaluation of the
      patient with prostate cancer or increased prostate specific antigen?

PMID- 23954249
TI  - Renal mass biopsy: "just do it".

PMID- 23954250
TI  - Editorial comment.

PMID- 23954251
TI  - Editorial comment.

PMID- 23954252
TI  - Can pharmaco-electroencephalography help improve survival of central nervous
      system drugs in early clinical development?
AB  - Pharmaco-electroencephalography has significant yet unrealised promise as a
      translatable intermediate biomarker of central pharmacodynamic activity that
      could help reduce Phase 2 attrition in the development of central nervous system
      drugs. In an effort to understand its true potential, a framework for decision
      making was proposed and the utility of pharmaco-electroencephalography was
      assessed through several case studies. A key finding was that lack of
      standardisation reduces the value of data pooling and meta-analyses and renders
      assessment of translatability difficult, limiting utility in all but simple
      cases. Pre-competitive collaboration is essential both to improving understanding
      of translation and developing modern signal processing techniques. 

PMID- 23954253
TI  - Clinical practice guidelines for treatment of exercise-associated hyponatremia.

PMID- 23954254
TI  - Molecular cloning and sequence analysis of prion protein gene in Xiji donkey in
      China.
AB  - Prion diseases are a group of human and animal neurodegenerative disorders caused
      by the deposition of an abnormal isoform prion protein (PrP(Sc)) encoded by a
      single copy prion protein gene (PRNP). Prion disease has been reported in many
      herbivores but not in Equus and the species barrier might be playing a role in
      resistance of these species to the disease. Therefore, analysis of genotype of
      prion protein (PrP) in these species may help understand the transmission of the
      disease. Xiji donkey is a rare species of Equus not widely reared in Ningxia,
      China, for service, food and medicine, but its PRNP has not been studied. Based
      on the reported PrP sequence in GenBank we designed primers and amplified, cloned
      and sequenced the PRNP of Xiji donkey. The sequence analysis showed that the Xiji
      donkey PRNP was consisted of an open reading frame of 768 nucleotides encoding
      256 amino acids. Amino acid residues unique to donkey as compared with some Equus
      animals, mink, cow, sheep, human, dog, sika deer, rabbit and hamster were
      identified. The results showed that the amino acid sequence of Xiji donkey PrP
      starts with the consensus sequence MVKSH, with almost identical amino acid
      sequence to the PrP of other Equus species in this study. Amino acid sequence
      analysis showed high identity within species and close relation to the PRNP of
      sika deer, sheep, dog, camel, cow, mink, rabbit and hamster with 83.1-99.7%
      identity. The results provided the PRNP data for an additional Equus species,
      which should be useful to the study of the prion disease pathogenesis, resistance
      and cross species transmission. 

PMID- 23954255
TI  - Interaction between gene A-positive Helicobacter pylori and human leukocyte
      antigen II alleles increase the risk of Graves disease in Chinese Han population:
      an association study.
AB  - OBJECTIVE: The current study explored the correlation of Helicobacter pylori and
      the polymorphisms of human leukocyte antigen II (HLA-II) alleles with Graves
      disease (GD). METHODS: A total of 216 patients with GD were recruited. 102
      healthy volunteers constituted the control group. Levels of H. pylori
      immunoglobulin G (IgG) antibodies and H. pylori cytotoxin-associated gene A
      (CagA) IgG antibodies were detected using enzyme-linked immunosorbent assays.
      Molecular typing of the HLA-II alleles was conducted using polymerase chain
      reaction with sequence specific primers. RESULTS: H. pylori, particularly CagA
      positive strains, HLA-DQA1 0201, and HLA-DQA1 0501 were associated with GD
      (P=0.015, OR=1.811; P=0.000, OR=3.085; P=0.000, OR=0.315; and P=0.004, OR=2.844,
      respectively). Patients with CagA-positive H. pylori and negative HLA-DQA1 0201
      or positive HLA-DQA1 0501 were more likely exposed to GD compared with those with
      only one of these indices. CONCLUSION: CagA-positive H. pylori, negative HLA-DQA1
      0201, or positive HLA-DQA1 0501 may increase the risk of GD.

PMID- 23954256
TI  - Extreme nearly neutral evolution in mitochondrial genomes of laboratory mouse
      strains.
AB  - Relaxation of the selective constraint during the domestication process is known.
      In this study, we report unexpected closeness to neutral evolution of
      mitochondrial genomes of laboratory mouse strains: estimated non
      synonymous/synonymous rate ratio being very close to 1 (omega^=1.32). Probably it
      is due to the extreme inbreeding extending over 100 years as well as to their
      recent origin (middle of the last millennium). There is no rate difference
      observed among three codon positions as well as ribosomal RNA and control
      regions. However, the amino acid substitutions occurred not randomly, and
      substitutions were more frequent between physico-chemically similar amino acids
      than between dissimilar ones. Probably this is inevitable consequence caused by
      the codon table itself, but not by selections. This implies that a large portion
      of the new mutations are conservative, and most of them are slightly deleterious
      and not lethal. It seems that, even though the selection pressures do not hold
      normally, the function of genes may not be impaired in most cases.

PMID- 23954257
TI  - Cloning and stress-responding expression analysis of malonyl CoA-acyl carrier
      protein transacylase gene of Nannochloropsis gaditana.
AB  - Malonyl CoA-acyl carrier protein transacylase (MCAT, E2.3.1.39) is closely
      associated with the FASII pathway of fatty acid biosynthesis. However, the
      information about microalgal MCAT is scarce. In this study, a MCAT gene was
      isolated from Nannochloropsis gaditana with its deduced protein (NgMCAT)
      characterized with bioinformatic tools. The abundance of the NgMCAT transcript
      under different environmental conditions was determined with real-time
      quantitative PCR. Results showed that the open reading frame (ORF) of NgMCAT was
      1059 bp in length, which encoded 352 amino acid residues. The abundance of NgMCAT
      transcript reached the maximum (5.17-fold) at 6h when sodium nitrate was limited,
      and reached the maximum (4.25-fold) at 12h at low temperature (15 degrees C). The
      abundance of NgMCAT transcript fluctuated at high temperature (35 degrees C) when
      the concentration of nitrate and sodium chloride exceeded 150 mg/L and 62 g/L,
      respectively. In addition, some components of fatty acid that changed with the
      expression of NgMCAT were also observed.

PMID- 23954258
TI  - Association of interleukin-13 SNP rs20541 (Arg>Gln) to allergic rhinitis in an
      Asian population of ethnic Chinese in Singapore.
AB  - In this study, we report our findings as we evaluated the association of IL-13
      SNP rs20541 to AR as reported in the meta-analysis (Ying, X-J et al., April, Gene
      2013) in an Asian population of 1322 ethnic Chinese recruited in Singapore well
      defined and characterized for allergic rhinitis. The SNP was significantly
      associated with AR at an odds ratio of 1.57 for the homozygous genotype
      comparisons indicating a strong risk for AR. This highlights the importance of
      this mutation in Asian populations for risk towards allergic phenotypes and also
      warrants further functional work to characterize the mechanism behind this
      genetic predisposition. 

PMID- 23954259
TI  - Decreased thrombomodulin mRNA expression on peripheral monocytes in disseminated
      intravascular coagulation patients relates to poor outcomes: the ex vivo effects
      of lipopolysaccharide and thrombin on monocyte thrombomodulin and CD14 mRNA.
AB  - BACKGROUND: Monocytes express substantial amounts of thrombomodulin, which is
      consumed throughout ongoing thrombin generation. The modulation of thrombomodulin
      may aggravate intravascular fibrin deposition and the clinical course of
      disseminated intravascular coagulation (DIC). Although thrombomodulin restoration
      has received considerable attention, no reports have been published on the in
      vivo expression status of thrombomodulin. CD14 expression on monocytes is
      important for regulation of the inflammatory response. We used an ex vivo
      stimulation study to evaluate the association of the levels of monocyte-expressed
      thrombomodulin and CD14 messenger RNA (mRNA) with the severity and prognosis of
      disseminated intravascular coagulation. METHODS: A total of 78 patients with
      suspected DIC were enrolled. Thrombomodulin and CD14 mRNA levels were measured in
      peripheral blood by real-time quantitative reverse-transcription polymerase chain
      reaction. Thrombomodulin and CD14 mRNA were also assessed in ex vivo cultures of
      peripheral whole blood that were stimulated by lipopolysaccharide or thrombin.
      RESULTS: The levels of monocyte-expressed thrombomodulin mRNA were significantly
      lower in the non-survivors than in the survivors. A low level of monocyte
      expressed thrombomodulin mRNA was a significant prognostic marker, but CD14 did
      not possess prognostic power. Monocyte-expressed CD14 mRNA correlated
      significantly with the severity of DIC in survivors. In addition, stimulation of
      ex vivo cultures of whole blood demonstrated that thrombin upregulates both
      thrombomodulin and CD14 mRNA, and lipopolysaccharide downregulates thrombomodulin
      mRNA. CONCLUSIONS: The downregulation of thrombomodulin on monocytes reflects the
      decompensated status of physiological defenses against hypercoagulopathy and
      represents the poor prognosis in DIC. The expression levels of thrombomodulin on
      monocytes may be a useful marker to screen for candidates eligible for
      recombinant thrombomodulin therapy in future.

PMID- 23954260
TI  - Fasciola hepatica - where is 28S ribosomal RNA?
AB  - Advanced molecular biology techniques are currently used to develop new effective
      strategies against fasciolosis. Assessment of the quality of extracted total RNA
      is an important step prior to commencing many molecular biology methods such as
      transcriptomics. However, RNA quality assessment is complicated for some
      organisms, including Fasciola hepatica, by the absence of a 28S rRNA peak/band,
      when assessed with modern protocols. In this study, electrophoretic profiles of
      F. hepatica ribosomal RNAs were evaluated using microfluidics capillary based and
      conventional non-denaturing gel electrophoresis methods. An important
      modification to recommended protocols, the exclusion of heat-denaturation step,
      in the microfluidics capillary based electrophoresis is critical to visualise the
      expected 28S rRNA and obtain an RNA integrity number (RIN). The intensity of the
      28S rRNA band is reduced by the effect of non-denaturing gel electrophoresis. 

PMID- 23954261
TI  - Dosimetric advantages and superior treatment delivery efficiency of RapidArc over
      conventional intensity-modulated radiotherapy in high-risk prostate cancer
      involving seminal vesicles and pelvic nodes.
AB  - AIMS: To compare the dosimetry and treatment delivery efficiency of RapidArc with
      conventional intensity-modulated radiotherapy (IMRT) in the treatment of high
      risk prostate cancer. MATERIALS AND METHODS: Fifteen patients with high-risk
      localised prostate cancer were studied. Sequential treatment was used. The
      initial planning target volume (PTV-L) included the prostate, seminal vesicles
      and pelvic lymphatics, whereas the prostate boost PTV (PTV-P) included the
      prostate and seminal vesicles only. The total prescription dose was 76 Gy (44 Gy
      to PTV-L, 32 Gy to PTV-P; 2 Gy/fraction). Two separate planning techniques were
      generated for each patient: seven static-field IMRT versus two-arc RapidArc. Dose
      volume parameters for the organs at risk, conformity index and homogeneity index
      for the PTVs, the calculated monitor units and treatment delivery time for both
      techniques were compared. RESULTS: RapidArc gave more conformal plans than IMRT
      for both PTVs. RapidArc gave a higher homogeneity index to the PTV-P and a
      similar homogeneity index to the PTV-L. The two techniques gave similar
      dosimetric results for the rectum, bladder and femoral heads. The mean dose
      (Dmean) and the maximum dose (Dmax) of the bowel space were reduced by 3.06 and
      2.83%, respectively, with RapidArc. The V20 Gy, V30 Gy and V40 Gy for healthy
      tissues were reduced by 7.77, 14.25 and 17.55%, respectively, with RapidArc. The
      calculated treatment delivery time and monitor units were reduced by
      74.09%/60.93% and 68.32%/48.06% for the PTV-L/PTV-P, respectively, with RapidArc.
      CONCLUSION: RapidArc is better than conventional IMRT in terms of dosimetry and
      delivery efficiency for high-risk prostate cancer.

PMID- 23954264
TI  - Shape, connectedness and dynamics in neuronal networks.
AB  - The morphology of neurons is directly related to several aspects of the nervous
      system, including its connectedness, health, development, evolution, dynamics
      and, ultimately, behavior. Such interplays of the neuronal morphology can be
      understood within the more general shape-function paradigm. The current article
      reviews, in an introductory way, some key issues regarding the role of neuronal
      morphology in the nervous system, with emphasis on works developed in the
      authors' group. The following topics are addressed: (a) characterization of
      neuronal shape; (b) stochastic synthesis of neurons and neuronal systems; (c)
      characterization of the connectivity of neuronal networks by using complex
      networks concepts; and (d) investigations of influences of neuronal shape on
      network dynamics. The presented concepts and methods are useful also for several
      other multiple object systems, such as protein-protein interaction, tissues,
      aggregates and polymers.

PMID- 23954263
TI  - Comparison of 2,2-bis(bromomethyl)-1,3-propanediol induced genotoxicity in UROtsa
      cells and primary rat hepatocytes: relevance of metabolism and oxidative stress.
AB  - 2,2-Bis(bromomethyl)-1,3-propanediol (BMP) is a brominated flame retardant used
      in urethane foams and polyester resins. In a two year dietary study, BMP caused
      neoplastic lesions at multiple sites including the urinary bladder of both rats
      and mice. However, liver was not a target tissue. We previously reported that BMP
      elicited oxidative DNA damage in a human uroepithelial cell line (UROtsa). The
      present in vitro study investigated the susceptibility of target (UROtsa cells)
      and non-target cells (primary rat hepatocytes) to BMP-induced genotoxicity. In
      contrast to hepatocytes, BMP exhibited greater genotoxic potential in UROtsa
      cells as evidenced by the concentration dependent increase in DNA strand breaks
      and DNA binding. Total content of intracellular GSH quantified in UROtsa cells
      (2.7+/-1.0nmol/mg protein) was 4 fold lower than that in hepatocytes (10.7+/
      0.3nmol/mg protein). HPLC analysis indicated BMP was not metabolized and/or
      consumed in UROtsa cells at any of the concentrations tested (10-250MUM) but was
      extensively converted to a mono-glucuronide in hepatocytes. These results
      demonstrate that a target cell line such as UROtsa cells are more susceptible to
      BMP-induced DNA damage when compared to non-target cells. This increased
      susceptibility may relate to the deficiency of antioxidant and/or metabolic
      capabilities in UROtsa cells. 

PMID- 23954265
TI  - An inexpensive, charge-balanced rodent deep brain stimulation device: a step-by
      step guide to its procurement and construction.
AB  - BACKGROUND: Despite there being a relatively large number of methods papers which
      detail specifically the development of stimulation devices, only a small number
      of reports involve the application of these devices in freely moving animals. To
      date multiple preclinical neural stimulators have been designed and described but
      have failed to make an impact on the methods employed by the majority of
      laboratories studying DBS. Thus, the overwhelming majority of DBS studies are
      still performed by tethering the subject to an external stimulator. We believe
      that the low adoption rate of previously described methods is a result of the
      complexity of replicating and implementing these methods. NEW METHOD: Here were
      describe both the design and procurement of a simple and inexpensive stimulator
      designed to be compatible with commonly used, commercially available electrodes
      (Plastics 1). RESULTS: This system is initially programmable in frequency,
      pulsewidth and current amplitude, and delivers biphasic, charge-balanced output
      to two independent electrodes. COMPARISON WITH EXISTING METHOD(S): It is easy to
      implement requiring neither subcutaneous implantation nor custom-made electrodes
      and has been optimized for either direct mounting to the head or for use with
      rodent jackets. CONCLUSIONS: This device is inexpensive and universally
      accessible, facilitating high throughput, low cost, long-term rodent deep brain
      stimulation experiments.

PMID- 23954266
TI  - Linking phospholipase C isoforms with differentiation function in human vascular
      smooth muscle cells.
AB  - The phosphoinositol-phospholipase C (PLC) family of enzymes consists of a number
      of isoforms, each of which has different cellular functions. PLCgamma1 is
      primarily linked to tyrosine kinase transduction pathways, whereas PLCdelta1 has
      been associated with a number of regulatory proteins, including those controlling
      the cell cycle. Recent studies have shown a central role of PLC in cell
      organisation and in regulating a wide array of cellular responses. It is of
      importance to define the precise role of each isoform, and how this changes the
      functional outcome of the cell. Here we investigated differences in PLC isoform
      levels and activity in relation to differentiation of human and rat vascular
      smooth muscle cells. Using Western blotting and PLC activity assay, we show that
      PLCdelta1 and PLCgamma1 are the predominant isoforms in randomly cycling human
      vascular smooth muscle cells (HVSMCs). Growth arrest of HVSMCs for seven days of
      serum deprivation was consistently associated with increases in PLCdelta1 and SM
      alpha-actin, whereas there were no changes in PLCgamma1 immuno-reactivity. Organ
      culture of rat mesenteric arteries in serum free media (SFM), a model of de
      differentiation, led to a loss of contractility as well as a loss of contractile
      proteins (SM alpha-actin and calponin) and PLCdelta1, and no change in PLCgamma1
      immuno-reactivity. Taken together, these data indicate that PLCdelta1 is the
      predominant PLC isoform in vascular smooth muscle, and confirm that PLCdelta1
      expression is affected by conditions that affect the cell cycle, differentiation
      status and contractile function. 

PMID- 23954262
TI  - Current therapy of myelodysplastic syndromes.
AB  - After being a neglected and poorly-understood disorder for many years, there has
      been a recent explosion of data regarding the complex pathogenesis of
      myelodysplastic syndromes (MDS). On the therapeutic front, the approval of
      azacitidine, decitabine, and lenalidomide in the last decade was a major
      breakthrough. Nonetheless, the responses to these agents are limited and most
      patients progress within 2 years. Allogeneic stem cell transplantation remains
      the only potentially curative therapy, but it is associated with significant
      toxicity and limited efficacy. Lack or loss of response after standard therapies
      is associated with dismal outcomes. Many unanswered questions remain regarding
      the optimal use of current therapies including patient selection, response
      prediction, therapy sequencing and combinations, and management of resistance. It
      is hoped that the improved understanding of the underpinnings of the complex
      mechanisms of pathogenesis will be translated into novel therapeutic approaches
      and better prognostic/predictive tools that would facilitate accurate risk
      adaptive therapy.

PMID- 23954267
TI  - Flecainide therapy suppresses exercise-induced ventricular arrhythmias in
      patients with CASQ2-associated catecholaminergic polymorphic ventricular
      tachycardia.
AB  - BACKGROUND: Calsequestrin-associated catecholaminergic polymorphic ventricular
      tachycardia (CPVT2) can cause sudden death in young individuals in response to
      stress. Beta-blockers are the mainstay medical treatment for patients with CPVT2.
      However, they do not prevent syncope and sudden death in all patients. Flecainide
      was reported to reduce exercise-induced ventricular arrhythmias (EIVA) in
      patients with ryanodine receptor-associated CPVT. The role of flecainide in CPVT2
      is not known. OBJECTIVE: To summarize our experience in combining flecainide and
      beta-blockers in high-risk patients with CPVT2. METHODS: All patients with CPVT2
      (10 patients) who have high-risk features (syncope, EIVA, or appropriate
      implantable cardioverter-defibrillator [ICD] shocks) despite beta-blockers with
      or without calcium channel blockers were treated with a combination of flecainide
      and beta-blockers. Exercise test was done before and after beginning treatment
      with flecainide. RESULTS: All patients had EIVA and 4 had appropriate ICD shocks
      before flecainide treatment. EIVA-included frequent ventricular premature beats
      and or ventricular tachycardia during the exercise test while on high dose of
      beta-blockers with or without calcium channel blockers before treatment with
      flecainide. After combination therapy with flecainide and beta-blockers, EIVA
      were suppressed completely in all patients. During follow-up of 15.5 +/- 10.4
      months (range 2-29 months), 8 patients were free of symptoms and free of
      arrhythmias. Two patients had 1 VT storm episode with recurrent ICD shocks
      despite repeated normal stress test. CONCLUSIONS: Flecainide can completely
      prevent ventricular arrhythmia during exercise and partially prevent recurrent
      ICD shocks in high-risk patients with CPVT2.

PMID- 23954268
TI  - Direct visualization of the left atrial appendage using esophageal radial
      endoscopic ultrasound: an alternative to TEE.

PMID- 23954269
TI  - Clinical outcomes after repair of left atrial esophageal fistulas occurring after
      atrial fibrillation ablation procedures.
AB  - BACKGROUND: The initial experience with left atrial esophageal fistula (LAEF)
      secondary to atrial fibrillation (AF) ablation procedures revealed a near
      universal mortality. A comprehensive description of the principles of LAEF repair
      in the modern era and its resulting impact on morbidity and mortality are lacking
      in the literature. OBJECTIVE: To describe the presentation, surgical management,
      and outcomes of patients with LAEF. METHODS: A retrospective cohort analysis of
      29 patients was performed, including previously unpublished cases of surgically
      repaired LAEF from 4 institutions (n = 6), and all published cases of surgically
      repaired (n = 16) or stented (n = 7) LAEF. RESULTS: The mean age was 55 +/- 13
      years, and 75% were men who were undergoing radiofrequency energy catheter
      ablation (n = 26), cryoablation (n = 1), high-intensity focused ultrasound
      ablation (n = 1), and surgical mini-MAZE procedure (n = 1) and presented 30 +/-
      12 days postablation procedure. Overall, 55% of the patients receiving an
      intervention for LAEF died (41% surgical repair; 100% stent). Patients who did
      not receive primary esophageal repair were more likely to experience
      postoperative complications, including mediastinitis, need for percutaneous
      endoscopic gastrostomy (PEG) feeds, esophageal stent, or death (P = .05). In
      addition, interposing tissue between the repaired esophagus and the left atrium
      resulted in fewer postoperative complications (P = .02). CONCLUSIONS: While
      improved relative to initial reports, mortality associated with LAEF remains high
      after corrective intervention. Primary esophageal repair with the placement of
      tissue between the repaired esophagus and the left atrium may result in lower
      morbidity and mortality.

PMID- 23954270
TI  - Production of human antibodies by in vitro immunization using a fusion protein
      containing the transcriptional transactivator of HIV-1.
AB  - Antigen-specific activation of human B cells represents a key step for the
      production of monoclonal antibodies. Several approaches have been developed over
      the last thirty years in order to improve the process of lymphocyte activation in
      vitro. In the present study, we investigated whether the transcriptional
      transactivator (Tat) of human immunodeficiency virus, which possesses numerous
      biological activities, is able to trigger antibody secretion when incubated with
      human peripheral blood mononuclear cells. No such effect was observed when using
      Tat as a free protein. However, we found a significant IgM antibody production
      when Tat was previously fused to a double domain, called ZZ, derived from protein
      A of Staphylococcus aureus. The effect was also observed when the fusion protein,
      called ZZTat101, was incubated with purified B cells, indicating that the
      phenomenon does not require T-cell help. Antibody secretion was observed in the
      absence of cytokines that are usually used during in vitro immunization
      experiments, indicating that ZZTat101 provides the signals required for the
      initiation of the immune response. Antibody secretion was observed using a ZZTat
      mutant, containing only the Tat residues 22 to 57, called ZZTat22-57, indicating
      that this region is sufficient to initiate the immune response. In contrast, the
      effect was not found with a ZZTat22-57 mutant devoid of the seven Tat cysteines
      located between residues 22 and 37, demonstrating that these residues play a
      crucial role in the phenomenon. Our results pave the way to the development of a
      new in vitro immunization method based on antigens associated with ZZTat. 

PMID- 23954271
TI  - Domestic cat microsphere immunoassays: detection of antibodies during feline
      immunodeficiency virus infection.
AB  - Microsphere immunoassays (MIAs) allow rapid and accurate evaluation of multiple
      analytes simultaneously within a biological sample. Here we describe the
      development and validation of domestic cat-specific MIAs for a) the
      quantification of total IgG and IgA levels in plasma, and b) the detection of IgG
      and IgA antibodies to feline immunodeficiency virus (FIV) capsid (CA) and surface
      (SU) proteins, and feline CD134 in plasma. These assays were used to examine the
      temporal antibody response of domestic cats infected with apathogenic and
      pathogenic FIVs, and domestic cats infected with parental and chimeric FIVs of
      varying pathogenicity. The results from these studies demonstrated that a) total
      IgG antibodies increase over time after infection; b) alpha-CA and alpha-SU IgG
      antibodies are detectable between 9 and 28 days post-infection and increase over
      time, and these antibodies combined represent a fraction (1.8 to 21.8%) of the
      total IgG increase due to infection; c) measurable alpha-CD134 IgG antibody
      levels vary among individuals and over time, and are not strongly correlated with
      viral load; d) circulating IgA antibodies, in general, do not increase during the
      early stage of infection; and e) total IgG, and alpha-CA and alpha-SU IgG
      antibody kinetics and levels vary with FIV viral strain/pathogenicity. The MIAs
      described here could be used to screen domestic cats for FIV infection, and to
      evaluate the FIV-specific or total antibody response elicited by various FIV
      strains/other diseases.

PMID- 23954272
TI  - Rapid detection and semi-quantification of IgG-accessible Staphylococcus aureus
      surface-associated antigens using a multiplex competitive Luminex assay.
AB  - The surface characterization of Staphylococcus aureus is currently labor
      intensive and time consuming. Therefore, we developed a novel method for the
      rapid yet comprehensive characterization of S. aureus cell-surface-associated
      proteins and carbohydrates, based on a competitive Luminex assay. In this assay,
      various S. aureus bacteria or culture supernatant dilutions are exposed to human
      pooled serum. S. aureus specific IgGs from the serum are captured to the IgG
      accessible staphylococcal antigens present on the bacterial surface, or in
      supernatant, in a dose dependent manner. The remaining non-captured IgGs are then
      quantified by incubation with Luminex beads to which the individual recombinant
      S. aureus surface proteins and carbohydrates are covalently linked. The signals
      obtained are inversely proportional to the antigen concentration measured, and
      binding patterns were dependent on the particular S. aureus isolate used, growth
      conditions and growth phase. For example, the detection of cell wall teichoic
      acid (WTA) and peptidoglycan (PG) carbohydrate structures increased significantly
      when bacteria entered the stationary growth phase, whereas the amounts of
      clumping factors (ClfA and ClfB) decreased significantly. Using this technique,
      the appearance of several S. aureus gene knockout strains were studied. We
      demonstrated that in an S. aureus srtA gene knockout strain, srtA-dependent cell
      surface-associated proteins were detectable yet not covalently linked to the PG
      layer. In conclusion, we show that this multiplex competitive Luminex assay is a
      suitable method for the rapid and simultaneous determination of S. aureus IgG
      accessible cell-surface-associated proteins and carbohydrates in various growth
      phases and growth conditions in different S. aureus strains. 

PMID- 23954273
TI  - Excess podocyte semaphorin-3A leads to glomerular disease involving plexinA1
      nephrin interaction.
AB  - Semaphorin-3A (Sema3a), a guidance protein secreted by podocytes, is essential
      for normal kidney patterning and glomerular filtration barrier development. Here,
      we report that podocyte-specific Sema3a gain-of-function in adult mice leads to
      proteinuric glomerular disease involving the three layers of the glomerular
      filtration barrier. Reversibility of the glomerular phenotype upon removal of the
      transgene induction provided proof-of-principle of the cause-and-effect
      relationship between podocyte Sema3a excess and glomerular disease.
      Mechanistically, excess Sema3a induces dysregulation of nephrin, matrix
      metalloproteinase 9, and alphavbeta3 integrin in vivo. Sema3a cell-autonomously
      disrupts podocyte shape. We identified a novel direct interaction between the
      Sema3a signaling receptor plexinA1 and nephrin, linking extracellular Sema3a
      signals to the slit-diaphragm signaling complex. We conclude that Sema3a
      functions as an extracellular negative regulator of the structure and function of
      the glomerular filtration barrier in the adult kidney. Our findings demonstrate a
      crosstalk between Sema3a and nephrin signaling pathways that is functionally
      relevant both in vivo and in vitro.

PMID- 23954274
TI  - Comparison of meat quality between eland (Taurotragus oryx) and cattle (Bos
      taurus) raised under similar conditions.
AB  - Physical, chemical and sensory characteristics of meat were compared between non
      domestic eland (Taurotragus oryx) bulls (n=6) and domestic Fleckvieh (Bos taurus)
      bulls (n=6) which were finished under controlled conditions of feeding and
      management. Musculus longissimus lumborum from eland were darker and less yellow
      in colour, with a higher pH24 and lower contents of intramuscular fat and total
      collagen, compared to cattle. Contents (mg/100 g muscle tissue) and proportions
      (g/100 g of FA determined) of SFA and MUFA were higher (P<0.01) in cattle.
      Although the proportion of total PUFA were higher (P<0.001) in eland, contents of
      PUFA were similar between species. Meat from cattle was consistently scored
      higher (P<0.05) for sensory texture characteristics, juiciness, flavour, and
      overall acceptance. We concluded that bulls of eland provided low-fat meat with a
      beneficial fatty acid composition from a human nutrition perspective, but with
      lower sensory scores, compared to bull beef.

PMID- 23954275
TI  - Nutritional composition of the meat of Hereford and Braford steers finished on
      pastures or in a feedlot in southern Brazil.
AB  - Chemical and mineral composition and the intramuscular fatty acid (IMF) profile
      of the Longissimus dorsi muscle (LM) of 60 purebred Hereford, 1/4 Braford and 3/8
      Braford steers finished either in a feedlot or on improved pastures of the Pampa
      biome were evaluated. Pastures were improved with the introduction of Lolium
      multiflorum, Trifolium repens, and Lotus corniculatus. On average, beef from
      pasture-fed steers presented higher concentrations of the fatty acids C18:3n-3
      (P<0.001), C20:3n-3 (P=0.035), total n-3 (P<0.001) and lower n-6/n-3 ratio
      (P<0.001) in the IMF, and higher Mg and lower K content in muscle relative to
      those finished in the feedlot. C12:0 concentration in IMF was higher (P=0.027)
      for 3/8 Braford than the purebred Hereford steers, whereas purebred Herefords
      presented lower C14:1 (P=0.003) and higher C18:0 (P=0.022) concentrations than
      the two Braford groups. The meat composition of purebred Hereford and Braford
      steers was not substantially different; however, beef produced exclusively on
      improved pastures presented higher concentration of components that are
      considered beneficial to human health, such as n-3 fatty acids, and a lower n-6/n
      3 ratio. 

PMID- 23954276
TI  - The retention and recovery of amino acids from pork longissimus muscle following
      cooking to either 60 degrees C or 75 degrees C.
AB  - Samples of pork longissimus muscle (n=16) cooked to either 60 degrees C or 75
      degrees C in a water bath for 90 min were assessed for amino acid composition.
      Recovery of protein in the cooked meat plus the cooking juice was >93% and was
      slightly higher at 60 degrees C (P=0.031), but retention in the meat was only 89%
      and 82% for the lower and higher temperatures (P<0.0001). Individual amino acids
      varied in recovery and retention with retention being particularly low for
      taurine and histidine. The balance of indispensable amino acids was less than
      ideal, with leucine and valine being the limiting amino acids by about 30% for
      both raw and cooked pork. Cooking had no detrimental effect on amino acid
      balance. Some examples of small effects of genotype and sex on amino acid
      composition of pork were shown.

PMID- 23954277
TI  - A prospective, randomized, double-blind, multicenter comparative study on the
      safety and efficacy of Celecoxib and GCSB-5, dried extracts of six herbs, for the
      treatment of osteoarthritis of knee joint.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This prospective, randomized, double-blind,
      multicenter study compared the efficacy and safety of Celecoxib and GCSB-5, a new
      product from extracts of six herbs, for the treatment of knee osteoarthritis.
      MATERIALS AND METHODS: A total of 198 eligible patients were randomly assigned to
      the Celecoxib group (n=99 patients) or the GCSB-5 group (n=99 patients) for the
      12-week study. The amount of change and percentage of the change in Western
      Ontario and McMaster Universities (WOMAC) Arthritis Index from the baseline, the
      change in pain on walking by visual analogue scale (VAS), physician's global
      assessment on response to therapy (PGART) by five point Likert scale, and the
      amount of rescue medicine taken were used as parameters for efficacy. Adverse
      drug reactions (ADRs) were carefully investigated. RESULTS: The WOMAC score
      improved in both the Celecoxib group and GCSB-5 group by 20.5 and 21.3 (P=0.79).
      The percentage of the change in WOMAC score were -42.0% and -38.9% (P=0.54). The
      pain VAS score decreased by 29.9 and 27.9 (P=0.58). The responders by PGART were
      95.3% and 93.8% (P= 0.66), and the median amount of rescue medicine taken were
      2.0 and 6.5 tablets (P=0.06). The incidence of ADRs were 31.3% and 21.2%
      (P=0.11). The most common ADRs were gastrointestinal system related; 17.2% in
      GCSB-5 group and 22.2% in Celecoxib group. Any severe ADR was not observed in
      either group. CONCLUSIONS: The result of this study supports that GCSB-5 is
      comparable to Celecoxib in terms of the efficacy and safety for the treatment of
      osteoarthritis of knee joint.

PMID- 23954279
TI  - Amelioration of Danhong injection on the lipopolysaccharide-stimulated systemic
      acute inflammatory reaction via multi-target strategy.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Systemic inflammatory response syndrome (SIRS),
      leading to dire consequences, is a serious and fatal disease in clinic. Danhong
      injection (DHI), one of the most popular medications for coronary heart disease
      and cerebral ischemia, plays pharmacological actions through inhibiting local
      inflammation. Nevertheless, the anti-inflammatory effect of DHI has not been
      reported before and has not been fully clarified. AIM OF THE STUDY: In this
      study, a model of systemic acute inflammatory reaction was induced by
      lipopolysaccharide (LPS) to investigate whether DHI could be applied to SIRS
      through the anti-inflammatory effect. MATERIAL AND METHODS: The anti-inflammatory
      effect of DHI in vivo was evaluated in ICR mice pretreated intraperitoneally
      (i.p.) with LPS (1mg/kg) and the serum, liver and kidney were collected.
      Interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and monocyte chemotactic
      protein (MCP-1) in serum were measured by enzyme-linked immunosorbent assay
      (ELISA) and the mRNA expressions of inducible NO synthase (iNOS), IL-6,
      interleukin (IL)-1beta, MCP-1 in mice liver and kidney were analyzed by
      quantitative real-time reverse-transcription polymerase chain reaction (real-time
      RT-PCR). Meanwhile, Proteome profiler array was used to screen the acute phase
      proteins, cytokines and chemokines activated in the acute inflammation. The
      inflammatory model of macrophages stimulated by LPS (0.2MUg/mL) was used to
      evaluate the anti-inflammatory mechanism of DHI in vitro. The secretion of nitric
      oxide (NO) was measured by the Griess reagent system. The productions of
      prostaglandin E2 (PGE2), IL-6, TNF-alpha and MCP-1 were detected using ELISA, and
      the protein expression of cyclooxygenase (COX)-2 was determined by cell-based
      ELISA. As well, the mRNA expressions of these inflammatory factors were detected
      by real-time RT-PCR. RESULTS: DHI could attenuate the inflammatory reaction via
      decreasing 20 cytokines and acute phase proteins analyzed by Proteome profile
      array in serum. The secretions of IL-6, TNF-alpha and MCP-1 in serum were
      coincidence with the result of Proteome profile array. Meanwhile, the mRNA
      expressions of iNOS, IL-6, IL-1beta, MCP-1 in mice liver and kidney were
      significantly reduced by DHI. Experiments performed in vitro further revealed
      that the productions of NO, PGE2 and the mRNA expressions of iNOS, COX-2 were
      notably inhibited by DHI. Cell-based ELISA revealed that the COX-2 protein
      expression was diminished by DHI. The results of ELISA demonstrated that DHI
      significantly down-regulated the protein productions of IL-6 and MCP-1.
      Furthermore, the mRNA expressions of iNOS, COX-2, TNF-alpha, IL-1beta, IL-6 and
      MCP-1 analyzed by real-time RT-PCR were suppressed by DHI. CONCLUSIONS: These
      results demonstrate that DHI exerts the protective effect through inhibiting the
      expressions of iNOS, COX-2, IL-1beta, IL-6, MCP-1 and TNF-alpha, which elucidate
      that DHI may be a strongly multi-target Chinese medicine injection on improving
      the inflammatory diseases.

PMID- 23954278
TI  - Gender-related pharmacokinetics and absolute bioavailability of diosbulbin B in
      rats determined by ultra-performance liquid chromatography-tandem mass
      spectrometry.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Diosbulbin B (DB) is the main constituent of
      furano-norditerpenes in Dioscorea bulbifera Linn., which is widely distributed in
      China and was usually used as a remedy for sore throat, struma and tumor. Owing
      to its potential antitumor activity, DB has been considered as a promising
      candidate for drug development. AIM OF THE STUDY: To study the pharmacokinetic
      properties and excretion of DB in rats by a sensitive UPLC-MS/MS method. Absolute
      bioavailability and gender-related pharmacokinetic properties, as well as
      excretion fractions of DB in urine and feces after oral and intravenous
      administrations would be addressed for the first time. MATERIALS AND METHODS:
      Sprague-Dawley rats were administrated orally (32mg/kg) and intravenously
      (0.5mg/kg) of DB, respectively. The concentrations of DB in rat plasma were
      determined by a sensitive and well-validated LC-MS/MS method. Main
      pharmacokinetic parameters including area under the plasma concentration-time
      curve (AUC), elimination half time (t1/2), mean residence time (MRT), apparent
      volume of distribution (Vd) and clearance rate (CL) were estimated using a non
      compartmental pharmacokinetics data analysis software. Urine and feces of rats
      were collected within 48h after oral administration (32mg/kg) and detected by
      UPLC-MS/MS and HPLC, respectively. RESULTS: The standard curves of DB in rat
      plasma and urine showed good linearity in the concentration range of 1.0-515ng/mL
      in the method, with acceptable selectivity, precisions, recoveries, and
      stability. The oral absolute bioavailability of DB in female rats was 2.0%,
      significantly higher than that of males (0.3%) (p<0.05). Female rats demonstrated
      longer t1/2 and MRT (p<0.01), bigger Vd and higher CL (p<0.05) than males after
      intravenous administration of DB. Bigger but no significant difference in
      excretion fractions of urine and feces in female rats were observed, comparing to
      those in males. CONCLUSION: A simple and sensitive UPLC-MS/MS method was
      developed to determine the pharmacokinetic profiles of DB in rats, as well as the
      excretion in rat urine. Gender exerted a significant influence on the
      pharmacokinetics and bioavailability of DB in rats. Female rats showed
      significantly better absorption of DB than males after oral administration.

PMID- 23954280
TI  - Modulation effect of Smilax glabra flavonoids on ryanodine receptor mediated
      intracellular Ca2+ release in cardiomyoblast cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Smilax glabra rhizome, a plant material from
      Liliaceae family, is a widely used traditional Chinese medicine for anti-cardiac
      hypertrophy treatment. We have previously found that Smilax glabra flavonoids
      (SGF) exerted such anti-cardiac hypertrophy activity. However, the mechanism of
      this activity of SGF has not been clarified yet. MATERIALS AND METHODS: This
      study was aimed to investigate the inhibitory role of SGF on intracellular Ca(2+)
      release in rat cardiomyoblast cells (H9C2). Intracellular Ca(2+) release was
      determined by Ca(2+) indicator fluorescence (fluo 4-AM) in H9C2 cell line.
      RESULTS: SGF at concentrations of 0.25, 0.5, 1.0mg/ml significantly inhibited the
      phenylephrine or angiotensin II induced intracellular Ca(2+) release in a dose
      dependent manner. Furthermore, SGF could also inhibit ryanodine receptor (RyR)
      agonist caffeine induced Ca(2+) release and phenylephrine (PE)-induced Ca(2+)
      release under the condition in which inositol trisphosphate (IP3) receptors were
      blocked with 2-Aminoethoxydiphenyl borate (2-APB). Nevertheless, SGF had no
      impact on PE-induced Ca(2+) release under the condition in which RyRs were
      blocked with tetracaine. CONCLUSIONS: Our results suggest that the protective
      effects of SGF are mediated via targeting inhibition of RyR mediated
      intracellular Ca(2+) release.

PMID- 23954281
TI  - A review on 129I analysis in air.
AB  - A review of literature focused on (129)I determination in air is provided. (129)I
      analysis in the environment represents a vital tool for tracing transport
      mechanisms, distribution pathways, safety assessment and its application as
      environmental tracer. To achieve that, specific chemical extraction methods and
      high sensitivity analytical techniques have been developed. This paper is
      intended to give an overview about the sample collection, extraction and
      distribution of (129)I in the air. Sensitivity of available measurement
      techniques for the determination of (129)I is compared. The article also provides
      the summary of current worldwide distribution of (129)I in air and respective
      radiation exposure of man. 

PMID- 23954282
TI  - Toll like receptor 2 agonists lipoteichoic acid and peptidoglycan are able to
      enhance antigen specific IFNgamma release in whole blood during recall antigen
      responses.
AB  - BACKGROUND: Interferon gamma release assays (IGRA) have been developed to support
      the diagnosis of diseases like tuberculosis, which lack robust serological test
      systems. IGRAs focus on cellular immunity especially memory T cells and thus
      complement serological testing. However, the low frequency of antigen-specific
      memory T cells in peripheral blood limits IFNgamma production to minute amounts
      and constitutes a major challenge for downstream test systems. We hypothesized
      that certain toll like receptor (TLR) agonists might enhance IFNgamma production
      in IGRAs after antigen challenge without inducing background cytokine production.
      In addition, we investigated the potential use of IL2 release after TLR agonist
      application as another surrogate marker in cytokine release assays. METHODS: 176
      healthy controls (HC) were tested for IFNgamma- and IL2-secretion in whole blood
      in the presence of different TLR agonists with and without antigen challenge by
      ELISA. The selected TLR agonists were lipopolysaccharide (LPS ? TLR4),
      lipoteichoic acid (LTA ? TLR2), peptidoglycan (PGN ? TLR2), zymosan (Zym ? TLR2
      and 6), polyinosinic-polycytidylic acid (Poly I:C ? TLR3), flagellin (Fla ?
      TLR5), R848 (?TLR7 and 8), loxoribine (Lox ? TLR7) and bropirimine (Bro ? TLR7).
      RESULTS: TLR2 agonists LTA and PGN increased IFNgamma secretion after antigen
      challenge nearly twofold (740 vs. 443 pg/ml for LTA and 969 vs. 469 pg/ml for
      PGN, respectively) without eliciting higher background expression. TLR3 agonist
      Poly(I:C) and TLR5 agonist Fla also induced a twofold increase in IFNgamma
      synthesis (2.230 vs. 1.085 pg/ml for Poly(I:C) and 518 vs. 278 pg/ml for Fla,
      respectively), but background expression was slightly increased (114 vs. 7 pg/ml
      for Poly(I:C) and 47 vs. 12 pg/ml for Fla, respectively). IL2 production was not
      increased after antigen challenge in the presence of LTA, PGN, Poly(I:C) or Fla.
      The agonists LPS, Zym, R848, Lox and Bro did not raise cytokine synthesis after
      antigen challenge or they generated high levels of cytokines by themselves.
      CONCLUSION: Of all tested agonists TLR2-specific LTA and PGN met the requirements
      to increase IFNgamma synthesis in whole blood after challenge with recall
      antigens without heightening basal cytokine levels alone. Thus, they constitute a
      potential costimulating reagent for IGRAs. IL2 did not show any potential as a
      surrogate marker in cytokine release assays in combination with TLR agonists.

PMID- 23954283
TI  - Optimization of the beam shaping assembly in the D-D neutron generators-based
      BNCT using the response matrix method.
AB  - Optimization of the Beam Shaping Assembly (BSA) has been performed using the
      MCNP4C Monte Carlo code to shape the 2.45 MeV neutrons that are produced in the D
      D neutron generator. Optimal design of the BSA has been chosen by considering in
      air figures of merit (FOM) which consists of 70 cm Fluental as a moderator, 30 cm
      Pb as a reflector, 2mm (6)Li as a thermal neutron filter and 2mm Pb as a gamma
      filter. The neutron beam can be evaluated by in-phantom parameters, from which
      therapeutic gain can be derived. Direct evaluation of both set of FOMs (in-air
      and in-phantom) is very time consuming. In this paper a Response Matrix (RM)
      method has been suggested to reduce the computing time. This method is based on
      considering the neutron spectrum at the beam exit and calculating contribution of
      various dose components in phantom to calculate the Response Matrix. Results show
      good agreement between direct calculation and the RM method.

PMID- 23954284
TI  - Elemental mapping of Moroccan enameled terracotta tile works (Zellij) based on X
      ray micro-analyses.
AB  - The purpose of this work is the elemental mapping of enameled terracotta samples
      (Zellij), produced between the 13th and 20th centuries in Morocco, collected from
      five different monuments from Marrakech. These pieces were analyzed by two non
      destructive micro X-Ray Fluorescence (XRF) spectrometers, aiming to obtain
      elemental distribution and elemental composition. From the obtained spectra we
      have identified the main elements present in the tin-opacified lead glaze. The
      identification of the decoration colors is based on the different ratios between
      the fluorescence lines of the main component of the glaze (Pb-Lalpha line) and
      the fluorescence lines of the main components of the pigment (Co-Kalpha, Mn
      Kalpha, Ni-Kalpha,... lines). The semi-quantitative calculations based on these
      ratios revealed significant differences between modern and ancient samples. 

PMID- 23954285
TI  - Genotoxic effects of bisphenol A on somatic cells of female mice, alone and in
      combination with X-rays.
AB  - Bisphenol A (BPA), a monomer used in the manufacture of epoxy, polycarbonate, and
      polystyrene resins, is a xenoestrogen present in many consumer products. We
      investigated the effects of 2-week exposure to BPA, either alone or in
      combination with X-rays, on the induction of DNA damage in somatic cells of
      female mice in vivo. The micronucleus and alkaline comet assays were used to
      evaluate genotoxicity. BPA induced DNA strand breaks in lung cells but not in
      bone marrow lymphocytes, liver, kidney, or spleen cells. Induction of micronuclei
      was observed only in polychromatic reticulocytes of peripheral blood. Levels of
      damage following combination exposure to ionizing radiation plus BPA depended on
      tissue, assay, and time. 

PMID- 23954286
TI  - Extending the limits of Bacillus for novel biotechnological applications.
AB  - Bacillus, generally regarded as safe, has emerged as a robust organism that can
      withstand adverse environmental conditions and grows easily to very high
      densities. Bacillus has been recognized for its biotechnological applications on
      an industrial scale. Recent efforts have shown the potential of Bacillus to
      generate biofuels (hydrogen), biopolymers (polyhydroxyalkanoates), and bioactive
      molecules (acyl-homoserine lactonases). Bacillus can be considered the dark horse
      in the race to generate sustainable energy, ecofriendly non-fossil fuel-based
      polymers, and bioactive molecules for use as therapeutics. 

PMID- 23954287
TI  - E2F1 activates p53 transcription through its distal site and participates in
      apoptosis induction in HPV-positive cells.
AB  - The p53 tumor suppressor protein, one of the most extensively studied proteins,
      plays a pivotal role in cellular checkpoints that respond to DNA damage to
      prevent tumorigenesis. However, the transcriptional control of the p53 gene has
      not been fully characterized. We report that the transcription factor E2F1 binds
      only to the E2F1 distal site of the p53 promoter in the human papillomavirus
      positive carcinoma HeLa cell line. Moreover, we showed that etoposide, a DNA
      damaging agent, activates p53 transcription through the E2F1 pathway. This
      increase correlates with apoptosis induction as disruption of this pathway led to
      reduced apoptosis stimulation by the DNA damaging agent. 

PMID- 23954288
TI  - Excision of 8-oxoguanine from methylated CpG dinucleotides by human 8-oxoguanine
      DNA glycosylase.
AB  - CpG dinucleotides are targets for epigenetic methylation, many of them bearing 5
      methylcytosine (mCyt) in the human genome. Guanine in this context can be easily
      oxidized to 8-oxoguanine (oxoGua), which is repaired by 8-oxoguanine-DNA
      glycosylase (OGG1). We have studied how methylation affects the efficiency of
      oxoGua excision from damaged CpG dinucleotides. Methylation of the adjacent
      cytosine moderately decreased the oxoGua excision rate while methylation opposite
      oxoGua lowered the rate of product release. Cytosine methylation abolished
      stimulation of OGG1 by repair endonuclease APEX1. The OGG1 S326C polymorphic
      variant associated with lung cancer showed poorer base excision and lost
      sensitivity to the opposite-base methylation. The overall repair in the system
      reconstituted from purified proteins decreased for CpG with mCyt in the damaged
      strand.

PMID- 23954289
TI  - Characterization of the supporting role of SecE in protein translocation.
AB  - SecYEG functions as a membrane channel for protein export. SecY constitutes the
      protein-conducting pore, which is enwrapped by SecE in a V-shaped manner. In its
      minimal form SecE consists of a single transmembrane segment that is connected to
      a surface-exposed amphipathic alpha-helix via a flexible hinge. These two domains
      are the major sites of interaction between SecE and SecY. Specific cleavage of
      SecE at the hinge region, which destroys the interaction between the two SecE
      domains, reduced translocation. When SecE and SecY were disulfide bonded at the
      two sites of interaction, protein translocation was not affected. This suggests
      that the SecY and SecE interactions are static, while the hinge region provides
      flexibility to allow the SecY pore to open. 

PMID- 23954290
TI  - FixL-like sensor FlbS of Brucella abortus binds haem and is necessary for
      survival within eukaryotic cells.
AB  - Replication of Brucella inside eukaryotic cells is essential for pathogenesis,
      and successful infection requires rapid adaptation to the intracellular milieu.
      Close relatives of Brucella use the two-component system FixLJ to survive inside
      the host. We aimed to identify a homologous sensor in Brucella abortus. A
      predicted protein with transmembrane and conserved histidine kinase domains was
      identified as the Fix-like Brucella sensor, FlbS. Although it lacks the PAS
      domain, recombinant FlbS binds haem in vitro. An internal in-frame deletion in
      flbS severely decreased B. abortus survival inside professional and non
      professional phagocytes. This phenotype was reverted by genetic complementation.
      These results indicate the critical role of this haemoprotein in the
      intracellular lifestyle of Brucella. 

PMID- 23954291
TI  - Influenza NS1 interacts with p53 and alters its binding to p53-responsive genes,
      in a promoter-dependent manner.
AB  - The interplay between influenza A viruses (IAV) and p53 has only been reported in
      a limited number of studies, mainly focusing on the antiviral role of p53. We
      investigated the impact of IAV infection on p53 stability and transcriptional
      activity. Our results indicate that IAV-induced stabilization of p53 only
      partially correlates with modulation of p53 transcriptional activity measured
      during infection. Moreover, we show that the viral non-structural protein 1 (NS1)
      is able to inhibit p53 transcriptional activity, in a promoter-dependent manner.
      Based on these data, we propose that NS1 may contribute to p53-mediated cell fate
      decision during IAV infection.

PMID- 23954292
TI  - Proteasome inhibition enhances resistance to DNA damage via upregulation of Rpn4
      dependent DNA repair genes.
AB  - The 26S proteasome is an ATP-dependent multi-subunit protease complex and the
      major regulator of intracellular protein turnover and quality control. However,
      its role in the DNA damage response is controversial. We addressed this question
      in yeast by disrupting the transcriptional regulation of the PRE1 proteasomal
      gene. The mutant strain has decreased proteasome activity and is hyper-resistant
      to various DNA-damaging agents. We found that Rpn4-target genes MAG1, RAD23, and
      RAD52 are overexpressed in this strain due to Rpn4 stabilisation. These genes
      represent three different pathways of base excision, nucleotide excision and
      double strand break repair by homologous recombination (DSB-HR). Consistently,
      the proteasome mutant displays increased DSB-HR activity. Our data imply that the
      proteasome may have a negative role in DNA damage response. 

PMID- 23954293
TI  - Downregulation of miR-16 promotes growth and motility by targeting HDGF in non
      small cell lung cancer cells.
AB  - MicroRNAs play important roles in the development and progression of non-small
      cell lung cancer (NSCLC). miR-16 functions as a tumor-suppressor and is inhibited
      in several malignancies. Herein, we validated that miR-16 is downregulated in
      NSCLC tissue samples and cell lines. Ectopic expression of miR-16 significantly
      inhibited cell proliferation and colony formation. Moreover, miR-16 suppressed
      cell migration and invasion in NSCLC cells. Hepatoma-derived growth factor (HDGF)
      was found to be a direct target of miR-16 in NSCLC cell lines. Rescue experiments
      showed that the suppressive effect of miR-16 on cell proliferation, colony
      formation, migration, and invasion is partially mediated by inhibiting HDGF
      expression. This study indicates that miR-16 might be associated with NSCLC
      progression, and suggests an essential role for miR-16 in NSCLC.

PMID- 23954294
TI  - Studies with the Plasmodium falciparum hexokinase reveal that PfHT limits the
      rate of glucose entry into glycolysis.
AB  - To characterise plasmodial glycolysis, we generated two transgenic Plasmodium
      falciparum lines, one expressing P. falciparum hexokinase (PfHK) tagged with GFP
      (3D7-PfHK(GFP)) and another overexpressing native PfHK (3D7-PfHK(+)). Contrary to
      previous reports, we propose that PfHK is cytosolic. The glucose analogue, 2
      deoxy-d-glucose (2-DG) was nearly 2-fold less toxic to 3D7-PfHK(+) compared with
      control parasites, supporting PfHK as a potential drug target. Although PfHK
      activity was higher in 3D7-PfHK(+), they accumulated phospho-[(14)C]2-DG at the
      same rate as control parasites. Transgenic parasites overexpressing the
      parasite's glucose transporter (PfHT) accumulated phospho-[(14)C]2-DG at a higher
      rate, consistent with glucose transport limiting glucose entry into glycolysis. 

PMID- 23954295
TI  - A single amino acid determines the catalytic efficiency of two alkenal double
      bond reductases produced by the liverwort Plagiochasma appendiculatum.
AB  - Alkenal double bond reductases (DBRs) catalyze the NADPH-dependent reduction of
      the alpha,beta-unsaturated double bond of many secondary metabolites. Two alkenal
      double bond reductase genes PaDBR1 and PaDBR2 were isolated from the liverwort
      species Plagiochasma appendiculatum. Recombinant PaDBR2 protein had a higher
      catalytic activity than PaDBR1 with respect to the reduction of the double bond
      present in hydroxycinnamyl aldehydes. The residue at position 56 appeared to be
      responsible for this difference in enzyme activity. The functionality of a C56 to
      Y56 mutation in PaDBR1 was similar to that of PaDBR2. Further site-directed
      mutagenesis and structural modeling suggested that the phenol ring stacking
      between this residue and the substrate was an important determinant of catalytic
      efficiency. 

PMID- 23954296
TI  - Sal-like 4 (SALL4) suppresses CDH1 expression and maintains cell dispersion in
      basal-like breast cancer.
AB  - In cell cultures, the dispersed phenotype is indicative of the migratory ability.
      Here we characterized Sal-like 4 (SALL4) as a dispersion factor in basal-like
      breast cancer. Our shRNA-mediated SALL4 knockdown system and SALL4 overexpression
      system revealed that SALL4 suppresses the expression of adhesion gene CDH1, and
      positively regulates the CDH1 suppressor ZEB1. Cell behavior analyses showed that
      SALL4 suppresses intercellular adhesion and maintains cell motility after cell
      cell interaction and cell division, which results in the dispersed phenotype. Our
      findings indicate that SALL4 functions to suppress CDH1 expression and to
      maintain cell dispersion in basal-like breast cancer. 

PMID- 23954297
TI  - Nicotinamide is a specific inhibitor of dark-operative protochlorophyllide
      oxidoreductase, a nitrogenase-like enzyme, from Rhodobacter capsulatus.
AB  - Dark-operative protochlorophyllide oxidoreductase (DPOR) is a nitrogenase-like
      enzyme consisting of two components, L-protein as a reductase component and NB
      protein as a catalytic component. Elucidation of the crystal structures of NB
      protein (Muraki et al., Nature 2010, 465: 110-114) has enabled us to study its
      reaction mechanism in combination with biochemical analysis. Here we demonstrate
      that nicotinamide (NA) inhibits DPOR activity by blocking the electron transfer
      from L-protein to NB-protein. A reaction scheme of DPOR, in which the binding of
      protochlorophyllide (Pchlide) to the NB-protein precedes the electron transfer
      from the L-protein, is proposed based on the NA effects. 

PMID- 23954298
TI  - Inhibition effect of enteropeptidase on RANKL-RANK signalling by cleavage of
      RANK.
AB  - Enteropeptidase can cleave trypsinogen on the sequence of Asp-Asp-Asp-Asp-Lys and
      plays an important role in food digestion. The RANKL-RANK signalling pathway
      plays a pivotal role in bone remodelling. In this study, we reported that
      enteropeptidase can inhibit the RANKL-RANK signalling pathway through the
      cleavage of RANK. A surrogate peptide blocking assay indicated that
      enteropeptidase could specifically cleave RANK on the sequence NEEDK. Osteoclast
      differentiation assay and NF-kappaB activity assay confirmed that enteropeptidase
      could inhibit osteoclastogenesis in vitro through the cleavage of RANK. This is
      the first study to prove that the RANKL-RANK signalling pathway can be inhibited
      by cleavage of RANK instead of targeting RANKL.

PMID- 23954300
TI  - Modelling nifedipine photodegradation, photostability and actinometric
      properties.
AB  - BACKGROUND: The photodegradation of drugs obeying unimolecular mechanisms such as
      that of nifedipine (NIF) were usually characterised in the literature by zero-,
      first- and second-order kinetics. This approach has been met with varying
      success. This paper addresses this issue and proposes a novel approach for
      unimolecular photodegradation kinetics. The photodegradation of the
      cardiovascular drug nifedipine is investigated within this framework. METHODS:
      Experimental kinetic data of nifedipine photodegradation were obtained by
      continuous monochromatic irradiation and DAD analysis. Fourth-order Runge-Kutta
      calculated kinetic data served for the validation of the new semi-empirical
      integrated rate-law model proposed in this study. RESULTS: A new model equation
      has been developed and proposed which faithfully describes the kinetic behaviour
      of NIF in solution for non-isosbestic irradiations at wavelengths where both NIF
      and its photoproduct absorb. NIF absolute quantum yield values were determined
      and found to increase with irradiation wavelength according to a defined sigmoid
      relationship. The effects of increasing NIF or excipients' concentrations on NIF
      kinetics were successfully modelled and found to improve NIF photostability. The
      potential of NIF for actinometry has been explored and evaluated. A new reaction
      order (the so-called Phi-order) has been identified and specifically proposed for
      unimolecular photodegradation reactions. CONCLUSION: The semi-empirical and
      integrated rate-law models facilitated reliable kinetic studies of NIF
      photodegradation as an example of AB(1Phi) unimolecular reactions. It allowed
      filling a gap in kinetic studies of drugs since, thus far, thermal first-order or
      a combination of first- and zero- order kinetic equations were generally applied
      for drug photoreactions in the literature. Also, a new reaction order, the "Phi
      order", has been evidenced and proposed as a specific alternative for
      photodegradation kinetics.

PMID- 23954299
TI  - Brain organization underlying superior mathematical abilities in children with
      autism.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder
      characterized by social and communication deficits. While such deficits have been
      the focus of most research, recent evidence suggests that individuals with ASD
      may exhibit cognitive strengths in domains such as mathematics. METHODS:
      Cognitive assessments and functional brain imaging were used to investigate
      mathematical abilities in 18 children with ASD and 18 age-, gender-, and IQ
      matched typically developing (TD) children. Multivariate classification and
      regression analyses were used to investigate whether brain activity patterns
      during numerical problem solving were significantly different between the groups
      and predictive of individual mathematical abilities. RESULTS: Children with ASD
      showed better numerical problem solving abilities and relied on sophisticated
      decomposition strategies for single-digit addition problems more frequently than
      TD peers. Although children with ASD engaged similar brain areas as TD children,
      they showed different multivariate activation patterns related to arithmetic
      problem complexity in ventral temporal-occipital cortex, posterior parietal
      cortex, and medial temporal lobe. Furthermore, multivariate activation patterns
      in ventral temporal-occipital cortical areas typically associated with face
      processing predicted individual numerical problem solving abilities in children
      with ASD but not in TD children. CONCLUSIONS: Our study suggests that superior
      mathematical information processing in children with ASD is characterized by a
      unique pattern of brain organization and that cortical regions typically involved
      in perceptual expertise may be utilized in novel ways in ASD. Our findings of
      enhanced cognitive and neural resources for mathematics have critical
      implications for educational, professional, and social outcomes for individuals
      with this lifelong disorder.

PMID- 23954301
TI  - Comparison of nested PCR and qPCR for the detection and quantitation of BoHV6
      DNA.
AB  - Nested PCR and qPCR (quantitative PCR) tests based on glycoprotein B (gB) gene
      were designed for detecting Bovine herpesvirus 6 (BoHV6) in bovine whole blood
      samples and wild ruminant blood clots (deer and roe-deer). This virus, commonly
      known as BLHV (bovine lymphotropic herpesvirus) belongs to the Herpesviridae
      family, subfamily Gammaherpesvirinae and Macavirus genus. DNA isolated from 92
      dairy cow blood samples and 69 wild ruminant clots were examined for the presence
      of BoHV6 using nested PCR and qPCR tests. Viral DNA was detected by using nested
      PCR in 59 out of 92 bovine blood samples (64.1%), and by qPCR in 68 out of 92
      bovine blood samples (73.9%), but none out of 69 DNA samples isolated from wild
      ruminant blood clots, was positive in both assays. The specificity of nested PCR
      and qPCR was confirmed by using BoHV1, BoHV4, BoHV6, BFV, BIV, and BLV DNA. The
      sensitivity of nested PCR and qPCR was determined using a serially 10-fold
      diluted vector pCR2.1HgB (2 * 10(0)-2 * 10(6)copies/reaction). In this testing,
      qPCR was more sensitive than the nested PCR, detecting two copies of BoHV6 whilst
      the limit of detection for nested PCR was 20 copies. In all qPCR assays, the
      coefficients of determination (R(2)) ranged between 0.990 and 0.999, and the
      calculated amplification efficiencies (Eff%) within the range of 89.7-106.9. The
      intra- and inter-assay CV (coefficient of variation) values did not exceed 4%.

PMID- 23954302
TI  - The influence of social evaluation on cerebral cortical activity and motor
      performance: a study of "Real-Life" competition.
AB  - Motor performance in a social evaluative environment was examined in participants
      (N = 19) who completed a pistol shooting task under both performance-alone (PA)
      and competitive (C) conditions. Electroencephalographic (EEG), autonomic, and
      psychoendocrine activity were recorded in addition to kinematic measures of the
      aiming behavior. State anxiety, heart rate, and cortisol were modestly elevated
      during C and accompanied by relative desynchrony of high-alpha power, increased
      cortico-cortical communication between motor and non-motor regions, and
      degradation of the fluency of aiming trajectory, but maintenance of performance
      outcome (i.e., score). The findings reveal that performance in a complex social
      evaluative environment characterized by competition results in elevated cortical
      activity beyond that essentially required for motor performance that translated
      as less efficient motor behavior.

PMID- 23954303
TI  - Effects of cue frequency and repetition on prospective memory: an ERP
      investigation.
AB  - Prospective memory involves the formation and completion of delayed intentions
      and is essential for independent living. In this study (n = 33), event-related
      potentials (ERPs) were used to systematically evaluate the effects of PM cue
      frequency (10% versus 30%) and PM cue repetition (high versus low) on ERP
      modulations. PM cues elicited prospective positivity and frontal positivity but
      not N300, perhaps due to the semantic nature of the task. Results of this study
      revealed an interesting interaction between PM cue frequency and PM cue
      repetition for prospective positivity and frontal positivity, highlighting the
      importance of taking both factors into account when designing future studies.

PMID- 23954304
TI  - Briefing in family characteristics of microRNAs and their applications in cancer
      research.
AB  - MicroRNAs (miRNAs) are endogenous, short, non-coding RNA molecules that are
      directly involved in the post-transcriptional regulation of gene expression.
      Dysregulation of miRNAs is usually associated with diseases. Since miRNAs in a
      family intend to have common functional characteristics, proper assignment of
      miRNA family becomes heuristic for better understanding of miRNA nature and their
      potentials in clinic. In this review, we will briefly discuss the recent progress
      in miRNA research, particularly its impact on protein and its clinical
      application in cancer research in a view of miRNA family. This article is part of
      a Special Issue entitled: Computational Proteomics, Systems Biology & Clinical
      Implications. Guest Editor: Yudong Cai. 

PMID- 23954305
TI  - Enzyme-substrate complexes of allosteric citrate synthase: evidence for a novel
      intermediate in substrate binding.
AB  - The citrate synthase (CS) of Escherichia coli is an allosteric hexameric enzyme
      specifically inhibited by NADH. The crystal structure of wild type (WT) E. coli
      CS, determined by us previously, has no substrates bound, and part of the active
      site is in a highly mobile region that is shifted from the position needed for
      catalysis. The CS of Acetobacter aceti has a similar structure, but has been
      successfully crystallized with bound substrates: both oxaloacetic acid (OAA) and
      an analog of acetyl coenzyme A (AcCoA). We engineered a variant of E. coli CS
      wherein five amino acids in the mobile region have been replaced by those in the
      A. aceti sequence. The purified enzyme shows unusual kinetics with a low affinity
      for both substrates. Although the crystal structure without ligands is very
      similar to that of the WT enzyme (except in the mutated region), complexes are
      formed with both substrates and the allosteric inhibitor NADH. The complex with
      OAA in the active site identifies a novel OAA-binding residue, Arg306, which has
      no functional counterpart in other known CS-OAA complexes. This structure may
      represent an intermediate in a multi-step substrate binding process where Arg306
      changes roles from OAA binding to AcCoA binding. The second complex has the
      substrate analog, S-carboxymethyl-coenzyme A, in the allosteric NADH-binding site
      and the AcCoA site is not formed. Additional CS variants unable to bind
      adenylates at the allosteric site show that this second complex is not a factor
      in positive allosteric activation of AcCoA binding. 

PMID- 23954307
TI  - Advances in lipase-catalyzed esterification reactions.
AB  - Lipase-catalyzed esterification reactions are among the most significant chemical
      and biochemical processes of industrial relevance. Lipases catalyze hydrolysis as
      well as esterification reactions. Enzyme-catalyzed esterification has acquired
      increasing attention in many applications, due to the significance of the derived
      products. More specifically, the lipase-catalyzed esterification reactions
      attracted research interest during the past decade, due to an increased use of
      organic esters in biotechnology and the chemical industry. Lipases, as
      hydrolyzing agents are active in environments, which contain a minimum of two
      distinct phases, where all reactants are partitioned between these phases,
      although their distribution is not fixed and changes as the reaction proceeds.
      The kinetics of the lipase-catalyzed reactions is governed by a number of
      factors. This article presents a thorough and descriptive evaluation of the
      applied trends and perspectives concerning the enzymatic esterification, mainly
      for biofuel production; an emphasis is given on essential factors, which affect
      the lipase-catalyzed esterification reaction. Moreover, the art of using
      bacterial and/or fungal strains for whole cell biocatalysis purposes, as well as
      carrying out catalysis by various forms of purified lipases from bacterial and
      fungal sources is also reviewed. 

PMID- 23954308
TI  - Discovery of an opportunistic starfish pathogen, Orchitophrya stellarum, in
      captive blue crabs, Callinectes sapidus.
AB  - Histophagous scuticociliate infections were discovered in blue crabs, Callinectes
      sapidus, held in research facilities at the Virginia Institute of Marine Science.
      Ciliates were observed infecting every tissue examined including the gills,
      heart, muscle, hepatopancreas, and epidermis. Hemolymph smears and histological
      tissue sections indicated a morphological similarity to Mesanophrys
      chesapeakensis, the only recorded histophagous ciliate infecting blue crabs.
      However, subsequent analysis of the ribosomal ITS region (ITS1-5.8S-ITS2) of the
      ciliate indicated the parasite was Orchitophrya stellarum, a parasitic ciliate
      previously reported infecting sea stars from Europe, Australia, and North
      America. A simple Polymerase Chain Reaction (PCR-RFLP) assay was developed to
      detect and differentiate between O. stellarum and M. chesapeakensis. Its
      application confirmed the presence of O. stellarum infecting blue crabs held in
      an additional research facility in Maryland. For growth studies, cultures of O.
      stellarum grew optimally on 10% blue crab serum in crustacean saline held at 10
      20 degrees C. A field survey of blue crabs collected during the winters of 2011
      2012 and sea stars (Asterias forbesi) during the winter of 2010 from the
      Chesapeake Bay and eastern shore of Virginia did not identify additional infected
      individuals. 

PMID- 23954306
TI  - Plasticity in the contribution of T cell receptor variable region residues to
      binding of peptide-HLA-A2 complexes.
AB  - One hypothesis accounting for major histocompatibility complex (MHC) restriction
      by T cell receptors (TCRs) holds that there are several evolutionary conserved
      residues in TCR variable regions that contact MHC. While this "germline codon"
      hypothesis is supported by various lines of evidence, it has been difficult to
      test. The difficulty stems in part from the fact that TCRs exhibit low affinities
      for pep/MHC, thus limiting the range of binding energies that can be assigned to
      these key interactions using mutational analyses. To measure the magnitude of
      binding energies involved, here we used high-affinity TCRs engineered by
      mutagenesis of CDR3. The TCRs included a high-affinity, MART-1/HLA-A2-specific
      single-chain TCR and two other high-affinity TCRs that all contain the same
      Valpha region and recognize the same MHC allele (HLA-A2), with different peptides
      and Vbeta regions. Mutational analysis of residues in CDR1 and CDR2 of the three
      Valpha2 regions showed the importance of the key germline codon residue Y51.
      However, two other proposed key residues showed significant differences among the
      TCRs in their relative contributions to binding. With the use of single-position,
      yeast-display libraries in two of the key residues, MART-1/HLA-A2 selections also
      revealed strong preferences for wild-type germline codon residues, but several
      alternative residues could also accommodate binding and, hence, MHC restriction.
      Thus, although a single residue (Y51) could account for a proportion of the
      energy associated with positive selection (i.e., MHC restriction), there is
      significant plasticity in requirements for particular side chains in CDR1 and
      CDR2 and in their relative binding contributions among different TCRs. 

PMID- 23954309
TI  - Surgical valvotomy and repair for neonatal and infant congenital aortic stenosis
      achieves better results than interventional catheterization.
AB  - OBJECTIVES: This study sought to compare outcomes after surgical valvuloplasty
      and balloon dilation of the aortic valve in neonates and infants. BACKGROUND:
      Surgical techniques of aortic valve repair have improved and there is today
      controversy on the best approach to treat neonatal congenital aortic valve
      stenosis. METHODS: Retrospective review of data and follow-up of 123 consecutive
      neonates and infants (35 females, 88 males) undergoing intervention for
      congenital aortic stenosis. RESULTS: From 1977 to 2009, 123 consecutive neonates
      (<30 days) and infants (31 days to 1 year) underwent relief of congenital aortic
      stenosis. Median age at procedure was 27 days (6 to 76 days). Twenty-year
      survival was 80 +/- 7%. Fifty-four patients required a re-intervention and
      freedom from re-intervention was 55 +/- 6% at 10 years and 40 +/- 6% at 20 years.
      By multivariate analysis, having the relief of stenosis by balloon valvuloplasty
      and undergoing initial treatment as a neonate were predictive of re-intervention.
      Freedom from re-intervention at 5 years was 27% after balloon valvuloplasty
      versus 65% after surgery. At latest follow-up, an additional 16 patients had
      moderate or severe stenosis and 8 had regurgitation. Freedom from re-intervention
      or stenosis was 39 +/- 5% at 15 years. By multivariate analysis, balloon
      valvuloplasty (p < 0.001) and treatment as a neonate (p = 0.003) were again
      predictive of stenosis or re-intervention. Thirty-five patients ultimately needed
      a valve replacement. Significant predictor of the requirement of valve
      replacement was unicuspid aortic valve (p < 0.001). Freedom from valve
      replacement was 55 +/- 7% at 20 years. CONCLUSIONS: Surgical valvuloplasty
      remains the best approach to treat neonates and infants with congenital aortic
      stenosis. After surgery, a higher proportion of patients remain free of re
      intervention than after interventional catheterization and the relief of their
      stenosis lasts longer.

PMID- 23954310
TI  - Neurologic and neurodevelopmental phenotypes in young children with early-treated
      combined methylmalonic acidemia and homocystinuria, cobalamin C type.
AB  - Abnormal neurodevelopment has been widely reported in combined methylmalonic
      aciduria (MMA) and homocystinuria, cblC type (cblC disease), but
      neurodevelopmental phenotypes in cblC have not previously been systematically
      studied. We sought to further characterize developmental neurology in children
      with molecularly-confirmed cblC. Thirteen children at our center with cblC, born
      since implementation of expanded newborn screening in New York State, undertook
      standard-of-care evaluations with a pediatric neurologist and pediatric
      ophthalmologist. At most recent follow-up (mean age 50 months, range 9-84
      months), of twelve children with early-onset cblC, three (25%) had a history of
      clinical seizures and two (17%) meet criteria for microcephaly. A majority of
      children had hypotonia and nystagmus. Twelve out of thirteen (92%) underwent
      neurodevelopmental evaluation (mean age 41 months; range 9-76 months), each child
      tested with standardized parental interviews and, where possible, age- and
      disability-appropriate neuropsychological batteries. All patients showed evidence
      of developmental delay with the exception of one patient with a genotype
      predictive of attenuated disease and near-normal biochemical parameters.
      Neurodevelopmental deficits were noted most prominently in motor skills, with
      relative preservation of socialization and communication skills. Nine children
      with early-onset cblC underwent magnetic resonance imaging and spectroscopy
      (MRI/MRS) at mean age of 47 months (range 6-81 months); common abnormalities
      included callosal thinning, craniocaudally short pons, and increased T2 FLAIR
      signal in periventricular and periatrial white matter. Our study further
      characterizes variable neurodevelopmental phenotypes in treated cblC, and
      provides insights into the etiopathogenesis of disordered neurodevelopment
      frequently encountered in cblC. Plasma homocysteine and MMA, routinely measured
      at clinical follow-up, may be poor predictors for neurodevelopmental outcomes.
      Additional data from large, prospective, multi-center natural history studies are
      required to more accurately define the role of these metabolites and others, as
      well as that of other genetic and environmental factors in the etiopathogenesis
      of the neurologic components of this disorder.

PMID- 23954311
TI  - Classifying temporal relations in clinical data: a hybrid, knowledge-rich
      approach.
AB  - We address the TLINK track of the 2012 i2b2 challenge on temporal relations.
      Unlike other approaches to this task, we (1) employ sophisticated linguistic
      knowledge derived from semantic and discourse relations, rather than focus on
      morpho-syntactic knowledge; and (2) leverage a novel combination of rule-based
      and learning-based approaches, rather than rely solely on one or the other.
      Experiments show that our knowledge-rich, hybrid approach yields an F-score of
      69.3, which is the best result reported to date on this dataset. 

PMID- 23954312
TI  - Digital video analysis of health professionals' interactions with an electronic
      whiteboard: a longitudinal, naturalistic study of changes to user interactions.
AB  - As hospital departments continue to introduce electronic whiteboards in real
      clinical settings a range of human factor issues have emerged and it has become
      clear that there is a need for improved methods for designing and testing these
      systems. In this study, we employed a longitudinal and naturalistic method in the
      usability evaluation of an electronic whiteboard system. The goal of the
      evaluation was to explore the extent to which usability issues experienced by
      users change as they gain more experience with the system. In addition, the paper
      explores the use of a new approach to collection and analysis of continuous
      digital video recordings of naturalistic "live" user interactions. The method
      developed and employed in the study included recording the users' interactions
      with system during actual use using screen-capturing software and analyzing these
      recordings for usability issues. In this paper we describe and discuss both the
      method and the results of the evaluation. We found that the electronic whiteboard
      system contains system-related usability issues that did not change over time as
      the clinicians collectively gained more experience with the system. Furthermore,
      we also found user-related issues that seemed to change as the users gained more
      experience and we discuss the underlying reasons for these changes. We also found
      that the method used in the study has certain advantages over traditional
      usability evaluation methods, including the ability to collect analyze live user
      data over time. However, challenges and drawbacks to using the method (including
      the time taken for analysis and logistical issues in doing live recordings)
      should be considered before utilizing a similar approach. In conclusion we
      summarize our findings and call for an increased focus on longitudinal and
      naturalistic evaluations of health information systems and encourage others to
      apply and refine the method utilized in this study. 

PMID- 23954314
TI  - Validation of endoscopic activity scores in patients with Crohn's disease based
      on a post hoc analysis of data from SONIC.
AB  - BACKGROUND & AIMS: Mucosal healing might alter midterm and long-term outcomes of
      patients with Crohn's disease (CD) and has become an important end point in
      clinical trials. However, the minimal degree of mucosal improvement (endoscopic
      response) required to alter midterm outcomes is not known. We aimed to determine
      the best definition of endoscopic response by evaluating data on the Simple
      Endoscopic Score for Crohn's Disease (SES-CD) and the Crohn's Disease Endoscopic
      Index of Severity (CDEIS) from the Study of Biologic and Immunomodulator Naive
      Patients in Crohn's Disease (SONIC trial). METHODS: We analyzed data from 172
      patients who participated in the SONIC trial, were found to have endoscopic
      lesions at baseline, and underwent a second endoscopic examination at week 26 of
      treatment with infliximab, azathioprine, or both. Mucosal healing was defined as
      absence of ulcers. A central reader calculated SES-CD and CDEIS results.
      Different cutoff values were set for endoscopic response based on the SES-CD or
      CDEIS. The diagnostic ability of these different cutoff values was evaluated
      using receiver operating characteristic (ROC) curves, positive likelihood ratios
      (PLR), and negative likelihood ratios (NLR). Corticosteroid-free clinical
      remission (CFREM) at week 50 was used as a binary classifier. RESULTS: Based on
      analyses of ROC curves, PLR, and NLR, endoscopic response was defined as a
      decrease from baseline in SES-CD of at least 50%. At week 26, mucosal healing and
      endoscopic response were achieved in 48% and 65% of patients, respectively.
      Mucosal healing at week 26 was associated with CFREM at week 50, with 56%
      sensitivity, 65% specificity, a PLR of 1.60, and an NLR of 0.67. Endoscopic
      response at week 26 was associated with CFREM at week 50, with 74% sensitivity,
      48% specificity, a PLR of 1.42, and an NLR of 0.54. Endoscopic response, defined
      as a decrease from baseline in CDEIS of at least 50%, yielded similar results.
      CONCLUSIONS: In patients with CD, mucosal healing and endoscopic response
      (defined as a decrease from baseline in SES-CD or CDEIS of at least 50%) at week
      26 of treatment identified those most likely to be in CFREM at week 50. The
      ability of the proposed endoscopic response cutoff value to predict midterm CFREM
      should be validated in an independent, prospective cohort. Its correlation with
      changes in long-term disease progression still needs to be demonstration.
      ClinicalTrials.gov, Number: NCT00094458.

PMID- 23954315
TI  - Delay in diagnosis of eosinophilic esophagitis increases risk for stricture
      formation in a time-dependent manner.
AB  - BACKGROUND & AIMS: Development of strictures is a major concern for patients with
      eosinophilic esophagitis (EoE). At diagnosis, EoE can present with an
      inflammatory phenotype (characterized by whitish exudates, furrows, and edema), a
      stricturing phenotype (characterized by rings and stenosis), or a combination of
      these. Little is known about progression of stricture formation; we evaluated
      stricture development over time in the absence of treatment and investigated risk
      factors for stricture formation. METHODS: We performed a retrospective study
      using the Swiss EoE Database, collecting data on 200 patients with symptomatic
      EoE (153 men; mean age at diagnosis, 39 +/- 15 years old). Stricture severity was
      graded based on the degree of difficulty associated with passing of the standard
      adult endoscope. RESULTS: The median delay in diagnosis of EoE was 6 years
      (interquartile range, 2-12 years). With increasing duration of delay in
      diagnosis, the prevalence of fibrotic features of EoE, based on endoscopy,
      increased from 46.5% (diagnostic delay, 0-2 years) to 87.5% (diagnostic delay,
      >20 years; P = .020). Similarly, the prevalence of esophageal strictures
      increased with duration of diagnostic delay, from 17.2% (diagnostic delay, 0-2
      years) to 70.8% (diagnostic delay, >20 years; P < .001). Diagnostic delay was the
      only risk factor for strictures at the time of EoE diagnosis (odds ratio = 1.08;
      95% confidence interval: 1.040-1.122; P < .001). CONCLUSIONS: The prevalence of
      esophageal strictures correlates with the duration of untreated disease. These
      findings indicate the need to minimize delay in diagnosis of EoE.

PMID- 23954313
TI  - Impaired emotional learning and involvement of the corticotropin-releasing factor
      signaling system in patients with irritable bowel syndrome.
AB  - BACKGROUND & AIMS: Alterations in central corticotropin-releasing factor
      signaling pathways have been implicated in the pathophysiology of anxiety
      disorders and irritable bowel syndrome (IBS). We aimed to characterize the
      effects of the corticotropin-releasing factor receptor 1 (CRF-R1) antagonist,
      GW876008, on brain and skin conductance responses during acquisition and
      extinction of conditioned fear to the threat of abdominal pain in subjects with
      IBS and healthy individuals (controls). METHODS: We performed a single-center,
      randomized, double-blind, 3-period crossover study of 11 women with IBS (35.50 +/
      12.48 years old) and 15 healthy women (controls) given a single oral dose (20 mg
      or 200 mg) of the CRF-R1 antagonist or placebo. Blood-oxygen level-dependent
      responses were analyzed using functional magnetic resonance imaging in a tertiary
      care setting. RESULTS: Controls had greater skin conductance responses during
      acquisition than extinction, validating the fear-conditioning paradigm. In
      contrast, during extinction, women with IBS had greater skin conductance
      responses than controls-an effect normalized by administration of a CRF-R1
      antagonist. Although the antagonist significantly reduced activity in the
      thalamus in patients with IBS and controls during acquisition, the drug produced
      greater suppression of blood-oxygen level-dependent activity in a wide range of
      brain regions in IBS patients during extinction, including the medial prefrontal
      cortex, pons, hippocampus, and anterior insula. CONCLUSIONS: Although CRF
      signaling via CRF-R1 is involved in fear acquisition and extinction learning
      related to expected abdominal pain in patients with IBS and controls, this system
      appears to be up-regulated in patients with IBS. This up-regulation might
      contribute to the previously reported abnormal brain responses to expected
      abdominal pain.

PMID- 23954316
TI  - What do the mirror system, embodied cognition, and synaesthesia have to do with
      each other?

PMID- 23954317
TI  - Functional and structural amygdala - anterior cingulate connectivity correlates
      with attentional bias to masked fearful faces.
AB  - An attentional bias to threat has been causally related to anxiety. Recent
      research has linked nonconscious attentional bias to threat with variability in
      the integrity of the amygdala - anterior cingulate pathway, which sheds light on
      the neuroanatomical basis for a behavioral precursor to anxiety. However, the
      extent to which structural variability in amygdala - anterior cingulate integrity
      relates to the functional connectivity within this pathway and how such
      functional connectivity may relate to attention bias behavior, remain critical
      missing pieces of the puzzle. In 15 individuals we measured the structural
      integrity of the amygdala - prefrontal pathway with diffusion tensor-weighted MRI
      (magnetic resonance imaging), amygdala-seeded intrinsic functional connectivity
      to the anterior cingulate, and attentional bias toward backward masked fearful
      faces with a dot-probe task. We found that greater biases in attention to threat
      predicted greater levels of uncinate fasciculus integrity, greater positive
      amygdala - anterior cingulate functional connectivity, and greater amygdala
      coupling with a broader social perception network including the superior temporal
      sulcus, tempoparietal junction (TPJ), and somatosensory cortex. Additionally,
      greater levels of uncinate fasciculus integrity correlated with greater levels of
      amygdala - anterior cingulate intrinsic functional connectivity. Thus, high bias
      individuals displayed a heightened degree of amygdala - anterior cingulate
      connectivity during basal conditions, which we believe predisposes these
      individuals to focus their attention on signals of threat within their
      environment. 

PMID- 23954318
TI  - Pure agraphia in Romaji after left inferior frontal gyrus infarction: A case of
      selective deficit in syllable-to-grapheme conversion in Japanese.
AB  - The Japanese writing system employs two distinct categories of characters: Kana
      and Kanji. The difference between Kana and Kanji writing corresponds roughly to
      that between phonological and lexical systems in Western languages. When typing,
      most Japanese use alphabetical characters based purely on phonological rules. In
      particular, the Romaji system is used, in which a syllable consists of a single
      vowel, a consonant-vowel compound (e.g., ka, ki), or a sequence of consonant
      y(semivowel)-vowel (e.g., kya, kyu). We describe a right-handed Japanese patient
      who developed pure agraphia that affected Romaji writing but preserved Kana and
      Kanji writing and who had a lesion in the left pars opercularis of the inferior
      frontal gyrus that extended to the anterior precentral gyrus. The patient
      demonstrated literal paragraphia in spelling Romaji across modalities. Our
      findings suggested that the patient's agraphia in Romaji after a confined left
      frontal infarction was manifested by a selective impairment in syllable-to
      grapheme conversion.

PMID- 23954319
TI  - Comment on "Measuring small compartments with relatively weak gradients by
      angular double-pulsed-field-gradient NMR" by Morozov Bar, Sochen, and Cohen.

PMID- 23954320
TI  - Early assessment of breast cancer response to neoadjuvant chemotherapy by semi
      quantitative analysis of high-temporal resolution DCE-MRI: preliminary results.
AB  - PURPOSE: To evaluate whether semi-quantitative analysis of high temporal
      resolution dynamic contrast-enhanced MRI (DCE-MRI) acquired early in treatment
      can predict the response of locally advanced breast cancer (LABC) to neoadjuvant
      chemotherapy (NAC). MATERIALS AND METHODS: As part of an IRB-approved prospective
      study, 21 patients with LABC provided informed consent and underwent high
      temporal resolution 3T DCE-MRI before and after 1cycle of NAC. Using measurements
      performed by two radiologists, the following parameters were extracted for
      lesions at both examinations: lesion size (short and long axes, in both early and
      late phases of enhancement), radiologist's subjective assessment of lesion
      enhancement, and percentages of voxels within the lesion demonstrating
      progressive, plateau, or washout kinetics. The latter data were calculated using
      two filters, one selecting for voxels enhancing >=50% over baseline and one for
      voxels enhancing >=100% over baseline. Pretreatment imaging parameters and
      parameter changes following cycle 1 of NAC were evaluated for their ability to
      discriminate patients with an eventual pathological complete response (pCR).
      RESULTS: All 21 patients completed NAC followed by surgery, with 9 patients
      achieving a pCR. No pretreatment imaging parameters were predictive of pCR.
      However, change after cycle 1 of NAC in percentage of voxels demonstrating
      washout kinetics with a 100% enhancement filter discriminated patients with an
      eventual pCR with an area under the receiver operating characteristic curve (AUC)
      of 0.77. Changes in other parameters, including lesion size, did not predict pCR.
      CONCLUSION: Semi-quantitative analysis of high temporal resolution DCE-MRI in
      patients with LABC can discriminate patients with an eventual pCR after one cycle
      of NAC.

PMID- 23954321
TI  - Anti-cancer effects of naturally occurring compounds through modulation of signal
      transduction and miRNA expression in human colon cancer cells.
AB  - Much evidence indicates that various naturally occurring compounds have an anti
      cancer effect, but the detailed mechanisms are not well understood. In this
      study, we selected anti-cancer phytochemicals such as epigallocatechin-3-gallate
      (EGCG), resveratrol (RES) and alpha-mangostin (alpha-M), all of which are well
      characterized chemopreventive agents. We sought to elucidate the mechanism of
      their anti-cancer effects and the synergistic effects obtained by combined
      treatment with the anti-cancer drug 5-fluorouracil (5-FU) in three human colon
      cancer cell lines. The numbers of viable cells were consistently decreased by the
      treatment with EGCG, RES or alpha-M at more than 10 MUM in all three cell lines
      tested. All compounds mainly induced apoptosis and suppressed the PI3K/Akt
      signaling pathway. Additionally, alpha-M, which had the greatest PI3K/Akt
      suppressing activity, also suppressed MAP kinase (MAPK)/Erk1/2 signaling.
      Importantly, the combination treatment with RES and 5-FU induced a remarkably
      synergistic enhancement of growth inhibition and apoptosis through the additional
      suppression of the MAPK/Erk1/2 signaling pathway in colon cancer DLD-1 cells.
      Interestingly, RES increased the intracellular expression level of miR-34a, which
      down-regulated the target gene E2F3 and its downstream Sirt1, resulting in growth
      inhibition. These findings indicate that these compounds functioned as
      chemosensitizers when combined with anti-cancer drugs through the modulation of
      apoptotic and growth-related signaling pathways. Also, RES exerted its anti
      cancer activity in part through a newly defined mechanism, i.e., the miR
      34a/E2F3/Sirt1 cascade. 

PMID- 23954322
TI  - Effective intranasal therapeutics and prophylactics with monoclonal antibody
      against lethal infection of H7N7 influenza virus.
AB  - Recurrence of highly pathogenic avian influenza (HPAI) virus subtype H7 in humans
      and poultry continues to be a serious concern to public health. No effective
      prevention and treatment are currently available against H7 infection. One H7
      monoclonal antibody, Mab 62 was selected and characterized. Mab 62 presented
      efficient neutralization activity against all six representative H7 strains
      tested, including the H7N9 strain from the recent outbreak in China. The epitope
      of 62 identified on H7 HA1 exists in all the human H7 strains, including the
      recent H7N9 strains from China. Mab 62 when administered passively, pre or post
      challenge with 5 MLD50 (50% mouse lethal dose) HPAI H7N7 influenza viruses could
      protect 100% of the mice from death. The efficacy of intranasal administration of
      the Mab was evaluated versus the intraperitoneal route. In the therapeutic study,
      body weight loss and virus load were reduced in intranasally inoculated mice, as
      compared to the intraperitoneal group. Intranasal administration results in early
      clearance of the virus from the lungs and completely prevents lung pathology of
      H7N7. The study confirmed that intranasal administration of Mab 62 is either an
      effective prophylactic or therapeutic means against H7 lethal infection. The
      results of epitope analysis suggest the potential of Mab 62 to be used for the
      efficacious prevention and treatment against the recent human H7N9 strains. 

PMID- 23954323
TI  - Antimalarial and safety evaluation of Pluchea lanceolata (DC.) Oliv. & Hiern: in
      vitro and in-vivo study.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Many of the effective therapeutic strategies have
      been derived from ethnopharmacologically used natural products. Pluchea
      lanceolata is an herb employed in Indian folk medicine for malaria like fever but
      it lacks proper pharmacological intervention. AIM OF THE STUDY: To evaluate
      antimalarial and safety profile of Pluchea lanceolata: an in-vitro, in-vivo for
      its ethnopharmacological validation. MATERIALS AND METHODS: Methanol, butanol,
      ethyl acetate, chloroform, hexane extracts and its isolate, taraxasterol acetate
      (TxAc) were obtained from air dried aerial part of Pluchea lanceolata. These were
      tested in-vitro against chloroquine-sensitive strain of Plasmodium falciparum
      NF54 by measuring the parasite specific lactate dehydrogenase activity. The most
      potent hexane extract and TxAc were further validated for in-vivo antimalarial
      and safety evaluation. TxAc, a pentacyclic-triterpene isolated from the most
      active fraction was further evaluated with special emphasis on inflammatory
      mediators involved in malaria pathogenesis. Murine malaria was induced by intra
      peritoneal injection of Plasmodium berghei infected red blood cells to the male
      Swiss inbred mice. Mice were orally treated following Peters 4-Day suppression
      test. In-vivo antimalarial efficacy was examined by evaluating the parasitaemia,
      percent survival, mean survival time, blood glucose, haemoglobin and pro
      inflammatory mediators involved in malaria pathogenesis. RESULTS: Hexane extract
      and TxAc showed promising antimalarial activity in-vitro and in-vivo condition.
      TxAc attributed in inhibition of the pro-inflammatory cytokines as well as afford
      to significant increase in the blood glucose and haemoglobin level when compared
      with vehicle treated infected mice. We have not observed the synergistic action
      of combinations of chloroquine and TxAc from our experimental results. In-vitro
      and in-vivo safety evaluation study revealed that hexane extract is non toxic at
      higher concentration. CONCLUSION: Present study further validates the ancient
      Indian traditional knowledge and use of Pluchea lanceolata as an antimalarial
      agent. Study confirms the suitability of Pluchea lanceolata as a candidate for
      further studies to obtain a prototype for antimalarial medicine.

PMID- 23954324
TI  - Antispasmodic effects and composition of the essential oils from two South
      American chemotypes of Lippia alba.
AB  - ETHOPHARMACOLOGY RELEVANCE: Lippia alba (Mill.) N. E. Brown (Verbenaceae) is an
      aromatic species used in Central and South America as eupeptic for indigestion.
      In Argentina, it is used by the "criollos" from the Chaco province. There are
      several chemotypes which differ in the chemical composition of the essential
      oils. Nowadays, it is experimentally cultivated in some countries of the region,
      including Argentina. AIM OF THE STUDY: To compare the chemical composition and
      pharmacology of the essential oils from two chemotypes: "citral" (CEO) and
      "linalool" (LEO), in isolated rat duodenum and ileum. METHODS: Contractile
      concentration-response curves (CRC) of acetylcholine (ACh) and calcium in 40mM
      K(+)-medium (Ca(2+)-CRC) were done in isolated intestine portions, in the absence
      and presence of CEO or LEO at different concentrations. RESULTS: Likewise
      verapamil, CEO and LEO induced a non-competitive inhibition of the ACh-CRC, with
      IC50 of 7.0+/-0.3mg CEO/mL and 37.2+/-4.2mg LEO/mL. l-NAME, a NO-synthase
      blocker, increased the IC50 of CEO to 26.1+/-8.7mg CEO/mL. Likewise verapamil,
      CEO and LEO non-competitively inhibited the Ca(2+)-CRC, with IC50 of 6.3+/-1.7mg
      CEO/mL, 7.0+/-2.5mg LEO/mL and 0.24+/-0.04mg verapamil/mL (pIC50: 6.28). CEO was
      proved to possess limonene, neral, geranial and (-)-carvone as the major
      components, while LEO was rich in linalool. CONCLUSIONS: Results suggest that CEO
      has five times more potency than LEO to inhibit muscarinic contractions. The
      essential oils of both chemotypes interfered with the Ca(2+)-influx, but with an
      IC50 about 28 times higher than that of verapamil. Moreover, CEO partially
      stimulated the NO production. These results show the medicinal usefulness of both
      Lippia alba chemotypes, thus validating its traditional use, potency and
      mechanism of action.

PMID- 23954325
TI  - An in vitro study on the maturation of conventional glass ionomer cements and
      their interface to dentin.
AB  - The objective of the study was to investigate the influence of long-term storage
      (up to 1 year) and coating on the variation of micro-mechanical properties of
      four conventional restorative glass ionomer cements (GICs) within 3.5 mm deep
      class I cavities. Four commercially available GICs (Riva Self Cure (SDI), ChemFil
      Rock (Dentsply), Fuji IX Fast and Fuji IX GP Extra/Equia (GC)) were applied to
      100 teeth. In each tooth, two similar 3.5 mm deep class I cavities were prepared
      and filled with the GICs, with and without resin coating. The samples were stored
      in artificial saliva at 37  degrees C for 1 week, 1 month, 3 months, 6 months and
      1 year. The variation in mechanical properties (indentation modulus (E) and
      Vickers hardness (HV)) were determined in 100 MUm steps starting from the filling
      surface, through the intermediate layer in between dentine and GIC, and ending
      100 MUm in dentin. HV and E were strongly influenced by the material (P<0.05,
      partial eta-squared etaP(2) = 0.31 and 0.23) but less by aging duration (P<0.05,
      etaP(2) = 0.02 and 0.12) and resin coating (P<0.05, etaP(2) = 0.02 and 0.03). The
      depth of measurement (0-2 mm) has no influence on HV (P = 0.789). HV shows a
      gentle increase over the 1 year storage period (P = 0.002). A ~300 MUm GIC zone
      at the areas close to dentin with weaker properties as those measured in dentin
      or GIC was identified in all fillings, irrespective of the presence of coating,
      and at all storage periods. The thickness of this zone is more strongly
      influenced by storage (P<0.05, etaP(2) = 0.081) than by material type (P<0.05,
      etaP(2) = 0.056), while coating showed no influence (P = 0.869). Filler
      morphology and dimension were similar to upper parts of the GIC filling; however,
      the amount of low cations was higher. We concluded that the development of an
      intermediate layer in between dentine and GIC with lower mechanical properties
      might be responsible for the bond quality of GIC to dentine. Moreover, class I
      GIC restorations are unlikely to feature constant mechanical properties
      throughout the cavity, regardless of conditions such as aging and coating.

PMID- 23954326
TI  - Selection of reference genes for gene expression studies in virus-infected
      monocots using quantitative real-time PCR.
AB  - Both genome-wide transcriptomic surveys of the mRNA expression profiles and virus
      induced gene silencing-based molecular studies of target gene during virus-plant
      interaction involve the precise estimation of the transcript abundance.
      Quantitative real-time PCR (qPCR) is the most widely adopted technique for mRNA
      quantification. In order to obtain reliable quantification of transcripts,
      identification of the best reference genes forms the basis of the preliminary
      work. Nevertheless, the stability of internal controls in virus-infected monocots
      needs to be fully explored. In this work, the suitability of ten housekeeping
      genes (ACT, EF1alpha, FBOX, GAPDH, GTPB, PP2A, SAND, TUBbeta, UBC18 and UK) for
      potential use as reference genes in qPCR were investigated in five different
      monocot plants (Brachypodium, barley, sorghum, wheat and maize) under infection
      with different viruses including Barley stripe mosaic virus (BSMV), Brome mosaic
      virus (BMV), Rice black-streaked dwarf virus (RBSDV) and Sugarcane mosaic virus
      (SCMV). By using three different algorithms, the most appropriate reference genes
      or their combinations were identified for different experimental sets and their
      effectiveness for the normalisation of expression studies were further validated
      by quantitative analysis of a well-studied PR-1 gene. These results facilitate
      the selection of desirable reference genes for more accurate gene expression
      studies in virus-infected monocots. 

PMID- 23954327
TI  - Construction of a 5'-controllable stabilizing element (CoSE) for over-production
      of heterologous proteins at high levels in Bacillus subtilis.
AB  - Different mRNA stabilizing elements including the 3'-stem-loop, the ribosome
      binding sites (RBS), the 5'-stem-loop and the spacer region between the RBS and
      the 5'-stem-loop were analysed in detail to increase mRNA stability resulting in
      enhanced expression of heterologous proteins. In addition, in combination with
      mRNA stabilizing elements, we propose a new class of 5'-mRNA controllable
      stabilizing element (CoSE) which is composed of a transcriptional operator such
      as lacO of the Escherichia coli lac operon and a suitable RBS followed by an
      optimal spacer length. Such a CoSE allowed Bacillus subtilis cells to synthesize
      extraordinary stable transcripts with a half-life of the model bgaB reporter
      transcript (codes for an beta-galactosidase gene derived from Bacillus
      stearothermophilus) of more than 60 min. This CoSE will be an important tool to
      control mRNA stability in cells for both research and biotechnological
      applications. For example, this CoSE can be used in inducible expression vectors
      offering two major advantages: (i) controlling transcription of target genes by
      the inducer and (ii) enhancing the stability of the transcript allowing the
      production high levels of recombinant proteins.

PMID- 23954328
TI  - Basic ingredients for mathematical modeling of tumor growth in vitro: cooperative
      effects and search for space.
AB  - Based on the literature data from HT-29 cell monolayers, we develop a model for
      its growth, analogous to an epidemic model, mixing local and global interactions.
      First, we propose and solve a deterministic equation for the progress of these
      colonies. Thus, we add a stochastic (local) interaction and simulate the
      evolution of an Eden-like aggregate by using dynamical Monte Carlo methods. The
      growth curves of both deterministic and stochastic models are in excellent
      agreement with the experimental observations. The waiting times distributions,
      generated via our stochastic model, allowed us to analyze the role of mesoscopic
      events. We obtain log-normal distributions in the initial stages of the growth
      and Gaussians at long times. We interpret these outcomes in the light of cellular
      division events: in the early stages, the phenomena are dependent each other in a
      multiplicative geometric-based process, and they are independent at long times.
      We conclude that the main ingredients for a good minimalist model of tumor
      growth, at mesoscopic level, are intrinsic cooperative mechanisms and competitive
      search for space. 

PMID- 23954329
TI  - Hebbian crosstalk and input segregation.
AB  - Hebbian synapses respond to input/output correlations, and thus to input
      statistical structure. However, recent evidence suggests that strength
      adjustments are not completely connection-specific, and this "crosstalk" could
      distort, or even prevent, learning processes. Crosstalk would then be a form of
      adjustment mistake, analogous to mistakes in polynucleotide copying. The mutation
      rate must be extremely low for successful evolution (which is a type of learning
      process), and similarly neural learning might require minimal crosstalk. We
      analyze aspects of the effect of crosstalk in Hebbian learning from pairwise
      input correlations, using the classical Oja model. In previous work we showed
      that crosstalk leads to learning of the principal eigenvector of EC (the input
      covariance matrix pre-multiplied by an error matrix that describes the crosstalk
      pattern), and found that, with positive input correlations, increasing crosstalk
      smoothly degrades performance. However, the Oja model requires negative input
      correlations to account for biological ocular segregation. Although this
      assumption is biologically somewhat implausible, it captures features that are
      seen in more complex models. Here, we analyze how crosstalk would affect such
      segregation. We show that, for statistically unbiased inputs, crosstalk induces a
      bifurcation from segregating to non-segregating outcomes at a critical value
      which depends on correlations. We also investigate the behavior in the vicinity
      of this critical state and for weakly biased inputs. Our results show that
      crosstalk can induce a bifurcation under special conditions even in the simplest
      Hebbian models, and that even the low levels of crosstalk observed in the brain
      could prevent normal development. However, during learning pairwise input
      statistics are more complex, and crosstalk-induced bifurcations may not occur in
      the Oja model. Such bifurcations would be analogous to "error catastrophes" in
      genetic models, and we argue that they are usually absent for simple linear
      Hebbian learning because such learning is only driven by pairwise correlations. 

PMID- 23954331
TI  - Lipokines and oxysterols: novel adipose-derived lipid hormones linking adipose
      dysfunction and insulin resistance.
AB  - The expansion of adipose tissue (AT) is, by definition, a hallmark of obesity.
      However, not all increases in fat mass are associated with pathophysiological
      cues. Indeed, whereas a "healthy" fat mass accrual, mainly in the subcutaneous
      depots, preserves metabolic homeostasis, explaining the occurrence of the
      metabolically healthy obese phenotype, "unhealthy" AT expansion is importantly
      associated with insulin resistance/type 2 diabetes and the metabolic syndrome.
      The development of a dysfunctional adipose organ may find mechanistic explanation
      in a reduced ability to recruit new and functional (pre)adipocytes from
      undifferentiated precursor cells. Such a failure of the adipogenic process
      underlies the "AT expandability" paradigm. The inability of AT to expand further
      to store excess nutrients, rather than obesity per se, induces a diabetogenic
      milieu by promoting the overflow and the ectopic deposition of fatty acids in
      insulin-dependent organs (i.e., lipotoxicity), the secretion of various
      metabolically detrimental adipose-derived hormones (i.e., adipokines and
      lipokines), and the occurrence of local and systemic inflammation and oxidative
      stress. Hitherto, fatty acids (i.e., lipokines) and the oxidation by-products of
      cholesterol and polyunsaturated fatty acids, such as nonenzymatic oxysterols and
      reactive aldehyde species, respectively, emerge as key modulators of
      (pre)adipocyte signaling through Wnt/beta-catenin and MAPK pathways and potential
      regulators of glucose homeostasis. These and other mechanistic insights linking
      adipose dysfunction, oxidative stress, and impairment of glucose homeostasis are
      discussed in this review article, which focuses on adipose peroxidation as a
      potential instigator of, and a putative therapeutic target for, obesity
      associated metabolic dysfunctions. 

PMID- 23954330
TI  - The Tudor domain of the PHD finger protein 1 is a dual reader of lysine
      trimethylation at lysine 36 of histone H3 and lysine 27 of histone variant H3t.
AB  - PHF1 associates with the Polycomb repressive complex 2 and it was demonstrated to
      stimulate its H3K27-trimethylation activity. We studied the interaction of the
      PHF1 Tudor domain with modified histone peptides and found that it recognizes
      H3K36me3 and H3tK27me3 (on the histone variant H3t) and that it uses the same
      trimethyllysine binding pocket for the interaction with both peptides. Since both
      peptide sequences are very different, this result indicates that reading domains
      can have dual specificities. Sub-nuclear localization studies of full-length PHF1
      in human HEK293 cells revealed that it co-localizes with K27me3, but not with
      K36me3, and that this co-localization depends on the trimethyllysine binding
      pocket indicating that K27me3 is an in vivo target for the PHF1 Tudor domain. Our
      data suggest that PHF1 binds to H3tK27me3 in human chromatin, and H3t has a more
      general role in Polycomb regulation. 

PMID- 23954333
TI  - Clinical manifestations of fibromuscular dysplasia vary by patient sex: a report
      of the United States registry for fibromuscular dysplasia.

PMID- 23954334
TI  - Comparison of transradial versus transfemoral percutaneous coronary intervention
      in routine practice: evidence for the importance of "falsification hypotheses" in
      observational studies of comparative effectiveness.

PMID- 23954335
TI  - Predictors and outcomes of side branch occlusion after main vessel stenting in
      coronary bifurcation lesions: results from the COBIS II Registry (COronary
      BIfurcation Stenting).
AB  - OBJECTIVES: This study sought to investigate the predictors and outcomes of side
      branch (SB) occlusion after main vessel (MV) stenting in coronary bifurcation
      lesions. BACKGROUND: SB occlusion is a serious complication that occurs during
      percutaneous coronary intervention (PCI) for bifurcation lesions. METHODS:
      Consecutive patients undergoing PCI using drug-eluting stents for bifurcation
      lesions with SB >=2.3 mm were enrolled. We selected patients treated with the 1
      stent technique or MV stenting first strategy. SB occlusion after MV stenting was
      defined as Thrombolysis in Myocardial Infarction flow grade <3. RESULTS: SB
      occlusion occurred in 187 (8.4%) of 2,227 bifurcation lesions. In multivariate
      analysis, independent predictors of SB occlusion were pre-procedural percent
      diameter stenosis of the SB >=50% (odds ratio [OR]: 2.34; 95% confidence interval
      [CI]: 1.59 to 3.43; p < 0.001) and the proximal MV >=50% (OR: 2.34; 95% CI: 1.57
      to 3.50; p < 0.001), SB lesion length (OR: 1.03; 95% CI: 1.003 to 1.06; p =
      0.03), and acute coronary syndrome (OR: 1.53; 95% CI: 1.06 to 2.19; p = 0.02). Of
      187 occluded SBs, flow was restored spontaneously in 26 (13.9%) and by SB
      intervention in 103 (55.1%) but not in 58 (31.0%). Jailed wire in the SB was
      associated with flow recovery (74.8% vs. 57.8%, p = 0.02). Cardiac death or
      myocardial infarction occurred more frequently in patients with SB occlusion than
      in those without SB occlusion (adjusted hazard ratio: 2.34; 95% CI: 1.15 to 4.77;
      p = 0.02). CONCLUSIONS: Angiographic findings of SB, proximal MV stenosis, and
      clinical presentation are predictive of SB occlusion after MV stenting. Occlusion
      of sizable SB is associated with adverse clinical outcomes..

PMID- 23954336
TI  - Dipyrone (metamizole) can nullify the antiplatelet effect of aspirin in patients
      with coronary artery disease.

PMID- 23954337
TI  - Predictive factors, management, and clinical outcomes of coronary obstruction
      following transcatheter aortic valve implantation: insights from a large
      multicenter registry.
AB  - OBJECTIVES: This study sought to evaluate the main baseline and procedural
      characteristics, management, and clinical outcomes of patients from a large
      cohort of patients undergoing transcatheter aortic valve implantation (TAVI) who
      suffered coronary obstruction (CO). BACKGROUND: Very little data exist on CO
      following TAVI. METHODS: This multicenter registry included 44 patients who
      suffered symptomatic CO following TAVI of 6,688 patients (0.66%). Pre-TAVI
      computed tomography data was available in 28 CO patients and in a control group
      of 345 patients (comparisons were performed including all patients and a cohort
      matched 1:1 by age, sex, previous coronary artery bypass graft, transcatheter
      valve type, and size). RESULTS: Baseline and procedural variables associated with
      CO were older age (p < 0.001), female sex (p < 0.001), no previous coronary
      artery bypass graft (p = 0.043), the use of a balloon-expandable valve (p =
      0.023), and previous surgical aortic bioprosthesis (p = 0.045). The left coronary
      artery was the most commonly involved (88.6%). The mean left coronary artery
      ostia height and sinus of Valsalva diameters were lower in patients with
      obstruction than in control subjects (10.6 +/- 2.1 mm vs. 13.4 +/- 2.1 mm, p <
      0.001; 28.1 +/- 3.8 mm vs. 31.9 +/- 4.1 mm, p < 0.001). Differences between
      groups remained significant after the case-matched analysis (p < 0.001 for
      coronary height; p = 0.01 for sinus of Valsalva diameter). Most patients
      presented with persistent severe hypotension (68.2%) and electrocardiographic
      changes (56.8%). Percutaneous coronary intervention was attempted in 75% of the
      cases and was successful in 81.8%. Thirty-day mortality was 40.9%. After a median
      follow-up of 12 (2 to 18) months, the cumulative mortality rate was 45.5%, and
      there were no cases of stent thrombosis or reintervention. CONCLUSIONS:
      Symptomatic CO following TAVI was a rare but life-threatening complication that
      occurred more frequently in women, in patients receiving a balloon-expandable
      valve, and in those with a previous surgical bioprosthesis. Lower-lying coronary
      ostium and shallow sinus of Valsalva were associated anatomic factors, and
      despite successful treatment, acute and late mortality remained very high,
      highlighting the importance of anticipating and preventing the occurrence of this
      complication.

PMID- 23954332
TI  - Prevalence of peripheral artery disease by abnormal ankle-brachial index in
      atrial fibrillation: implications for risk and therapy.

PMID- 23954338
TI  - Anatomic versus physiologic assessment of coronary artery disease. Role of
      coronary flow reserve, fractional flow reserve, and positron emission tomography
      imaging in revascularization decision-making.
AB  - Angiographic severity of coronary artery stenosis has historically been the
      primary guide to revascularization or medical management of coronary artery
      disease. However, physiologic severity defined by coronary pressure and/or flow
      has resurged into clinical prominence as a potential, fundamental change from
      anatomically to physiologically guided management. This review addresses clinical
      coronary physiology-pressure and flow-as clinical tools for treating patients. We
      clarify the basic concepts that hold true for whatever technology measures
      coronary physiology directly and reliably, here focusing on positron emission
      tomography and its interplay with intracoronary measurements. 

PMID- 23954339
TI  - Childhood obesity and cardiovascular dysfunction.
AB  - Obesity-related cardiovascular disease in children is becoming more prevalent in
      conjunction with the rise in childhood obesity. Children with obesity are
      predisposed to an increased risk of cardiovascular morbidity and mortality in
      adulthood. Importantly, research in children with obesity over the last decade
      has demonstrated that children may exhibit early signs of cardiovascular
      dysfunction as a result of their excess adiposity, often independent of other
      obesity-related comorbidities such as dyslipidemia and insulin resistance. The
      clinical evidence is accumulating to suggest that the cardiovascular damage, once
      observed only in adults, is also occurring in obese children. The objective of
      this review is to provide a synopsis of the current research on cardiovascular
      abnormalities in children with obesity and highlight the importance and need for
      early detection and prevention programs to mitigate this potentially serious
      health problem. 

PMID- 23954340
TI  - Tearing into the heart: dissociation of aortic cusp with rupture of the
      interventricular septum.

PMID- 23954341
TI  - Cystic tuberculous pericarditis.

PMID- 23954342
TI  - Thinking outside the lumen: fractional flow reserve versus intravascular imaging
      for major adverse cardiac event prediction.

PMID- 23954343
TI  - Benefits of statins in elderly subjects without established cardiovascular
      disease: a meta-analysis.
AB  - OBJECTIVES: The purpose of this paper was to assess whether statins reduce all
      cause mortality and cardiovascular (CV) events in elderly people without
      established CV disease. BACKGROUND: Because of population aging, prevention of CV
      disease in the elderly is relevant. In elderly patients with previous CV events,
      the use of statins is recommended by guidelines, whereas the benefits of these
      drugs in elderly subjects without previous CV events are still debated. METHODS:
      Randomized trials comparing statins versus placebo and reporting all-cause and CV
      mortality, myocardial infarction (MI), stroke, and new cancer onset in elderly
      subjects (age >= 65 years) without established CV disease were included. RESULTS:
      Eight trials enrolling 24,674 subjects (42.7% females; mean age 73.0 +/- 2.9
      years; mean follow up 3.5 +/- 1.5 years) were included in analyses. Statins,
      compared with placebo, significantly reduced the risk of MI by 39.4% (relative
      risk [RR]: 0.606 [95% confidence interval (CI): 0.434 to 0.847]; p = 0.003) and
      the risk of stroke by 23.8% (RR: 0.762 [95% CI: 0.626 to 0.926]; p = 0.006). In
      contrast, the risk of all-cause death (RR: 0.941 [95% CI: 0.856 to 1.035]; p =
      0.210) and of CV death (RR: 0.907 [95% CI: 0.686 to 1.199]; p = 0.493) were not
      significantly reduced. New cancer onset did not differ between statin- and
      placebo-treated subjects (RR: 0.989 [95% CI: 0.851 to 1.151]; p = 0.890).
      CONCLUSIONS: In elderly subjects at high CV risk without established CV disease,
      statins significantly reduce the incidence of MI and stroke, but do not
      significantly prolong survival in the short-term.

PMID- 23954345
TI  - Impaired secondary oxidant deactivation capacity and enhanced oxidative stress in
      serum from alveld affected lambs.
AB  - Alveld is a hepatogenous photosensitivity disorder in lambs. The aim of the study
      was to investigate if alveld affected lambs had a reduced capacity to handle
      oxidative stress induced from either endogenous and/or exogenous
      photosensitizers. Serum samples from alveld lambs (n=33) were compared to serum
      samples from control lambs (n=31) and exposed to a controlled amount of singlet
      oxygen ((1)O2). The sera from alveld lambs were found to have an impaired ability
      to deactivate reactive oxygen species (ROS) compared to control sera. A higher
      degree of initial hemolysis and a higher concentration of the exogenous
      photosensitizer phytoporphyrin (PP) were detected in alveld sera compared to the
      controls. The action spectrum for the formation of (1)O2 indicated that PP as
      well as the endogenous compound protoporphyrin IX (PP IX) may act as in vivo
      photosensitizers. A relatively high level of iron was detected in pooled serum
      from alveld lambs that showed a high degree of hemolysis. It was concluded that
      alveld photosensitivity is likely to be initiated by a photodynamic reaction
      involving PP and possibly also PP IX followed by a light-independent reaction
      involving hemoglobin-related products and catalysis by the Fenton reaction. 

PMID- 23954344
TI  - Noninvasive monitoring of serial changes in pulmonary vascular resistance and
      acute vasodilator testing using cardiac magnetic resonance.
AB  - OBJECTIVES: The study sought to evaluate the ability of cardiac magnetic
      resonance (CMR) to monitor acute and long-term changes in pulmonary vascular
      resistance (PVR) noninvasively. BACKGROUND: PVR monitoring during the follow-up
      of patients with pulmonary hypertension (PH) and the response to vasodilator
      testing require invasive right heart catheterization. METHODS: An experimental
      study in pigs was designed to evaluate the ability of CMR to monitor: 1) an acute
      increase in PVR generated by acute pulmonary embolization (n = 10); 2) serial
      changes in PVR in chronic PH (n = 22); and 3) changes in PVR during vasodilator
      testing in chronic PH (n = 10). CMR studies were performed with simultaneous
      hemodynamic assessment using a CMR-compatible Swan-Ganz catheter. Average flow
      velocity in the main pulmonary artery (PA) was quantified with phase contrast
      imaging. Pearson correlation and mixed model analysis were used to correlate
      changes in PVR with changes in CMR-quantified PA velocity. Additionally, PVR was
      estimated from CMR data (PA velocity and right ventricular ejection fraction)
      using a formula previously validated. RESULTS: Changes in PA velocity strongly
      and inversely correlated with acute increases in PVR induced by pulmonary
      embolization (r = -0.92), serial PVR fluctuations in chronic PH (r = -0.89), and
      acute reductions during vasodilator testing (r = -0.89, p <= 0.01 for all). CMR
      estimated PVR showed adequate agreement with invasive PVR (mean bias -1.1 Wood
      units,; 95% confidence interval: -5.9 to 3.7) and changes in both indices
      correlated strongly (r = 0.86, p < 0.01). CONCLUSIONS: CMR allows for noninvasive
      monitoring of acute and chronic changes in PVR in PH. This capability may be
      valuable in the evaluation and follow-up of patients with PH.

PMID- 23954346
TI  - Implication of the TRPM4 nonselective cation channel in mammalian sinus rhythm.
AB  - BACKGROUND: The transient receptor potential melastatin 4 (TRPM4) channel is
      expressed in the sinoatrial node, but its physiologic roles in this tissue with
      cardiac pacemaker properties remain unknown. This Ca(2+)-activated nonselective
      cation channel (NSCCa) induces cell depolarization at negative potentials. It is
      implicated in burst generation in neurons and participates in induction of
      ectopic beating in cardiac ventricular preparations submitted to
      hypoxia/reoxygenation. Accordingly, TRPM4 may participate in action potential
      (AP) triggering in the sinoatrial node. OBJECTIVE: The purpose of this study was
      to investigate the influence of TRPM4 on spontaneous heart beating. METHODS:
      Spontaneous APs were recorded using intracellular microelectrodes in mouse, rat,
      and rabbit isolated right atria. RESULTS: In the spontaneously beating mouse
      atrium, superfusion of the TRPM4-specific inhibitor 9-phenanthrol produced a
      concentration-dependent reduction in AP rate (maximal reduction = 62% that of
      control; EC50 = 8 * 10(-6) mol?L(-1)) without affecting other AP parameters.
      These effects were absent in TRPM4(-/-) mice. 9-Phenanthrol exerted a rate
      dependent reduction with a higher effect at low rates. Similar results were
      obtained in rat. Moreover, application of 9-phenanthrol produced a reduction in
      diastolic depolarization slope in rabbit sinus node pacemaker cells. CONCLUSION:
      These data showed that TRPM4 modulates beating rate. Pacemaker activity in the
      sinoatrial node results from the slow diastolic depolarization slope due to the
      "funny" current, Na/Ca exchange, and a Ca(2+)-activated nonselective cation
      current, which can be attributable in part to TRPM4 that may act against
      bradycardia.

PMID- 23954349
TI  - Vitamin D and food allergy in patients with severe atopic dermatitis.

PMID- 23954348
TI  - Protons as second messenger regulators of G protein signaling.
AB  - In response to environmental stress, cells often generate pH signals that serve
      to protect vital cellular components and reprogram gene expression for survival.
      A major barrier to our understanding of this process has been the identification
      of signaling proteins that detect changes in intracellular pH. To identify
      candidate pH sensors, we developed a computer algorithm that searches proteins
      for networks of proton-binding sidechains. This analysis indicates that Galpha
      subunits, the principal transducers of G protein-coupled receptor (GPCR) signals,
      are pH sensors. Our structure-based calculations and biophysical investigations
      reveal that Galpha subunits contain networks of pH-sensing sidechains buried
      between their Ras and helical domains. Further, we show that proton binding
      induces changes in conformation that promote Galpha phosphorylation and suppress
      receptor-initiated signaling. Together, our computational, biophysical, and
      cellular analyses reveal an unexpected function for G proteins as mediators of
      stress-response signaling. 

PMID- 23954350
TI  - Reply: To PMID 23453797.

PMID- 23954347
TI  - Haemolysin coregulated protein is an exported receptor and chaperone of type VI
      secretion substrates.
AB  - Secretion systems require high-fidelity mechanisms to discriminate substrates
      among the vast cytoplasmic pool of proteins. Factors mediating substrate
      recognition by the type VI secretion system (T6SS) of Gram-negative bacteria, a
      widespread pathway that translocates effector proteins into target bacterial
      cells, have not been defined. We report that haemolysin coregulated protein
      (Hcp), a ring-shaped hexamer secreted by all characterized T6SSs, binds
      specifically to cognate effector molecules. Electron microscopy analysis of an
      Hcp-effector complex from Pseudomonas aeruginosa revealed the effector bound to
      the inner surface of Hcp. Further studies demonstrated that interaction with the
      Hcp pore is a general requirement for secretion of diverse effectors encompassing
      several enzymatic classes. Though previous models depict Hcp as a static conduit,
      our data indicate it is a chaperone and receptor of substrates. These unique
      functions of a secreted protein highlight fundamental differences between the
      export mechanism of T6 and other characterized secretory pathways. 

PMID- 23954351
TI  - Lower levels of hsa-mir-15a, which decreases VEGFA, in the CD4+ T cells of
      pediatric patients with asthma.

PMID- 23954352
TI  - Thin endometrium in donor oocyte recipients: enigma or obstacle for implantation?
AB  - OBJECTIVE: To evaluate the combined effect of endometrial thickness and anatomic
      uterine factors on clinical outcome in oocyte donation recipients. DESIGN:
      Retrospective analysis of oocyte donation cycles conducted between 2005 and 2010.
      SETTING: Two private IVF centers. PATIENT(S): A total of 737 donor oocyte cycles.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy and live birth
      rates. RESULT(S): No statistically significant difference was found in clinical
      pregnancy rates and live birth rates in cycles with endometrial thickness <6 mm
      compared with those with endometrial thickness >10 mm. However, a relatively high
      rate of live births was found within a medium range of endometrial thickness (8.2
      10 mm). All intrauterine adhesion cases occurred in cycles with thinner
      endometrium. CONCLUSION(S): No statistically significant difference was found in
      clinical pregnancy rates and live birth rates in cycles with endometrial
      thickness <6 mm compared with those with thickness >6 mm. A relatively high rate
      of live births was found within a medium range of endometrial thickness (9.1-10
      mm).

PMID- 23954353
TI  - Reporting of clinical outcomes in assisted reproductive technology.

PMID- 23954354
TI  - 2-Methoxyestradiol in the human corpus luteum throughout the luteal phase and its
      influence on lutein cell steroidogenesis and angiogenic activity.
AB  - OBJECTIVE: To quantitate 2-methoxyestradiol (2-ME) in human corpus luteum (CL) of
      different ages and to determine the expression of cytochrome-P450-1A1 (CYP1A1)
      and catechol-O-methyl transferase (COMT) in CL and the action of 2-ME on P,
      vascular endothelial growth factor (VEGF) secretion, and luteal angiogenesis.
      DESIGN: Experimental study. SETTING: University division of reproductive
      endocrinology. PATIENT(S): Twenty-four women of reproductive age.
      INTERVENTION(S): CL was collected from 15 women during the minilaparotomy for
      tubal sterilization. Granulosa lutein cells were harvested 36 hours after hCG
      administration in patients undergoing IVF. MAIN OUTCOMES MEASURE(S): Levels of 2
      ME were determined by high-performance liquid chromatography in CL. CYP1A1 and
      COMT were assessed by immunohistochemistry and Western blot. P and VEGF were
      measured by radioimmunoassay and ELISA. The angiogenic potential was analyzed
      using EA.hy926 cells. RESULT(S): Plasma levels of E2 decreased in the late luteal
      phase in association with an increase in luteal tissue of 2-ME concentrations.
      Concomitantly, there was a significant reduction of angiogenic activity in late
      CL. There was no significant variation in CYP1A1 and COMT expression in all CL.
      In physiological doses, 2-ME inhibited basal VEGF by granulosa lutein cells and
      diminished the angiogenic activity in conditioned media but did not prevent P and
      VEGF production stimulated by hCG. CONCLUSION(S): These data suggest the
      participation of 2-ME in physiological luteolysis by reducing angiogenesis.
      However, 2-ME did not prevent in vitro hCG stimulation of P biosynthesis,
      providing a mechanism for CL rescue in the cycle of conception.

PMID- 23954355
TI  - Reply of the authors.

PMID- 23954356
TI  - Growth differential factor-9 inhibits testosterone production in mouse theca
      interstitial cells.
AB  - OBJECTIVE: To explore the effect of growth differential factor-9 (GDF-9) alone on
      cell proliferation, cell viability, steroidogenesis, and hormone-stimulated gene
      expression in cultured mouse theca interstitial cells. DESIGN: Basic research.
      SETTING: University hospital. ANIMAL(S): Immature 3- to 4-week-old SPF KM mice
      obtained from the Laboratory Animal Center of Sun Yat-Sen University.
      INTERVENTION(S): Addition of GDF-9 at different dosages to primary culture of
      mouse theca interstitial cells. MAIN OUTCOME MEASURE(S): Cell number, cell
      viability, progesterone and testosterone levels, and hormone-stimulated gene mRNA
      abundance. RESULT(S): Growth differential factor-9 mildly increased the number of
      mouse theca interstitial cells and cell viability in a dose-dependent manner and
      mildly inhibited the production of progesterone in mouse theca interstitial
      cells. Administration of GDF-9 at the dosages of 200 ng/mL and 400 ng/mL resulted
      in a significant decrease in the testosterone level compared with the control
      group by 60.42% and 68.76%, respectively. Growth differential factor-9
      significantly suppressed Lhcgr mRNA by 47.36%, Cyp11a1 mRNA by 62.30%, and
      Cyp17a1 mRNA by 55.39%, but had only a mild effect on Star gene expression.
      CONCLUSION(S): Growth differential factor-9 can inhibit the production of
      testosterone in mouse theca interstitial cells and suppress the corresponding
      gene expression.

PMID- 23954357
TI  - Impact of subclinical hypothyroidism in women with recurrent early pregnancy
      loss.
AB  - OBJECTIVE: To assess the impact of subclinical hypothyroidism (SCH) in women with
      recurrent early pregnancy loss (REPL). DESIGN: Observational cohort study.
      SETTING: REPL program in an academic medical center. PATIENT(S): 286 women with a
      history of >=2 pregnancy losses <10 weeks. INTERVENTION(S): From 2004-2007, no
      treatment for women with SCH (thyroid-stimulating hormone [TSH] >2.5 mIU/L with a
      normal free thyroxine or free thyroxine index); from 2008 onward, levothyroxine
      treatment prepregnancy to maintain TSH <=2.5 mIU/L. MAIN OUTCOME MEASURE(S): Live
      birth rate (LBR). RESULT(S): The prevalence of SCH was 55 (19%) of 286 in this
      REPL cohort. The cumulative LBR was 27 (69%) of 39 for women with SCH versus 104
      (74%) of 141 for euthyroid women. The per-pregnancy LBR was 34 (49%) of 69 for
      SCH versus 129 (58%) of 221 for euthyroid women. When the LBR was compared
      between treated and untreated SCH, the cumulative LBR was 17 (71%) of 24 versus
      10 (67%) of 15, respectively. The per-pregnancy LBR for SCH treated versus
      untreated women was 22 (48%) of 46 versus 12 (52%) of 23, respectively.
      CONCLUSION(S): Although there was a high prevalence of SCH in the REPL cohort,
      there was no statistically significant difference in the subsequent live-birth
      rate when comparing women with SCH and euthyroid women, or treated and untreated
      SCH.

PMID- 23954359
TI  - Reply of the authors.

PMID- 23954358
TI  - Developmental exposure of fetal ovaries and fetal germ cells to endometriosis in
      an endometriosis model causes differential gene expression in the preimplantation
      embryos of the first-generation and second-generation embryos.
AB  - OBJECTIVE: To characterize multigenerational gene expression anomalies in eight
      cell stage embryos associated with developmental exposure to endometriosis.
      DESIGN: Using an endometriosis model in rats (F0 founder generation) to evaluate
      gene expression in F1 (fetal exposure) and F2 (fetal germ cell exposure)
      generation eight-cell stage embryos. SETTING: Laboratory. ANIMAL(S):
      Endometriosis model in rats (Endo) and controls (Sham). INTERVENTION(S): F0 Endo
      and Sham rats were bred; half the pregnant rats were killed on gestational day 3
      to collect F1 eight-cell stage embryos and the others gestated to term (F1
      females). Adult F1 females bred; F2 eight-cell embryos collected. MAIN OUTCOME
      MEASURE(S): Maintenance of differential gene expression in F1 and F2 generation
      eight-cell embryos in endometriosis. RESULT(S): Developmental exposure to
      endometriosis altered the gene signaling pathways, with changes found in
      apoptosis, the cell cycle process, the response to oxidative stress, negative
      regulation of molecular function, and RNA processing. The apoptotic genes Diablo,
      Casp3, Parp1, Cad, and Dnaja3 were increased and the Nfkbia transcripts were
      decreased in F1 Endo versus F1 Sham embryos. In F2 Endo versus Sham embryos,
      Casp3 and Cad were statistically significantly increased, and Parp1 and Nfkbia
      tended to be elevated. CONCLUSION(S): Fetal and germ cell exposure to
      endometriosis alters apoptotic gene expression in first- and second-generation
      eight-cell stage embryos, supporting the hypothesis of multigenerational
      inheritance resulting from exposure to endometriosis in utero.

PMID- 23954360
TI  - Biomarkers of endometriosis.

PMID- 23954361
TI  - Sustained ventricular tachycardia caused by anaphylactic reaction.
AB  - We report a 30-year-old man who developed severe anaphylactic reactions with
      sustained ventricular tachycardia after eating seafood. This case emphasizes the
      need for cardiac monitoring in patients with anaphylaxis to identify malignant
      ventricular arrhythmias early.

PMID- 23954362
TI  - Sternal fracture after cardioversion: time to probe.

PMID- 23954363
TI  - Reduced AgRP activation in the hypothalamus of cows with high extent of fat
      mobilization after parturition.
AB  - Agouti-related protein (AgRP), produced by neurons located in the arcuate nucleus
      of the hypothalamus stimulates feed intake. During early lactation dairy cows
      increase their feed intake and additionally mobilize their fat reserves leading
      to increased plasma non-esterified fatty acid (NEFA) concentrations. Since cows
      with a higher extent of fat mobilization exhibit the lower feed intake, it seems
      that high NEFA concentrations confine hyperphagia. To test the involvement of
      AgRP neurons, we investigated 18 cows from parturition until day 40 postpartum
      (pp) and assigned the cows according to their NEFA concentration on day 40pp to
      either group H (high NEFA) or L (low NEFA). Both groups had comparable feed
      intake, body weight, milk yield, energy balance, plasma amino acids and leptin
      concentrations. Studies in respiratory chambers revealed the higher oxygen
      consumption and the lower respiratory quotient (RQ) in H compared to L cows. mRNA
      abundance of neuropeptide Y, peroxisome proliferator-activated receptor-gamma,
      AMP-activated protein kinase, and leptin receptor in the arcuate nucleus were
      comparable between groups. Immunohistochemical studies revealed the same number
      of AgRP neurons in H and L cows. AgRP neurons were co-localized with
      phosphorylated adenosine monophosphate-activated kinase without any differences
      between groups. The percentage of cFOS-activated AgRP neurons per total AgRP
      cells was lower in H cows and correlated negatively with oxygen consumption and
      NEFA, positively with RQ, but not with feed intake. We conclude that AgRP
      activation plays a pivotal role in the regulation of substrate utilization and
      metabolic rate in high NEFA dairy cows during early lactation. 

PMID- 23954364
TI  - beta2-Adrenoceptor agonists in the regulation of mitochondrial biogenesis.
AB  - The stimulation of mitochondrial biogenesis (MB) via cell surface G-protein
      coupled receptors is a promising strategy for cell repair and regeneration. Here
      we report the specificity and chemical rationale of a panel of beta2-adrenoceptor
      agonists with regards to MB. Using primary cultures of renal cells, a diverse
      panel of beta2-adrenoceptor agonists elicited three distinct phenotypes: full MB,
      partial MB, and non-MB. Full MB compounds had efficacy in the low nanomolar range
      and represent two chemical scaffolds containing three distinct chemical clusters.
      Interestingly, the MB phenotype did not correlate with reported receptor affinity
      or chemical similarity. Chemical clusters were then subjected to pharmacophore
      modeling creating two models with unique and distinct features, consisting of
      five conserved amongst full MB compounds were identified. The two discrete
      pharmacophore models were coalesced into a consensus pharmacophore with four
      unique features elucidating the spatial and chemical characteristics required to
      stimulate MB. 

PMID- 23954365
TI  - Identification of a family of four UDP-polypeptide N-acetylgalactosaminyl
      transferases in Cryptosporidium species.
AB  - Although mucin-type O-glycans are critical for Cryptosporidium infection, the
      enzymes catalyzing their synthesis have not been studied. Here, we report four
      UDP N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyl
      transferases (ppGalNAc-Ts) from the genomes of C. parvum, C. hominis and C.
      muris. All are Type II membrane proteins which include a cytoplasmic tail, a
      transmembrane domain, a stem region, a glycosyltransferase family 2 domain and a
      C-terminal ricin B lectin domain. All are expressed during C. parvum infection in
      vitro, with Cp-ppGalNAc-T1 and -T4 expressed at 24 h and Cp-ppGalNAc-T2 and -T3
      at 48 and 72 h post-infection, suggesting that their expression may be
      developmentally regulated. C. parvum sporozoite lysates display ppGalNAc-T
      enzymatic activity against non-glycosylated and pre-glycosylated peptides
      suggesting that they contain enzymes capable of glycosylating both types of
      substrates. The importance of mucin-type O-glycans in Cryptosporidium-host cell
      interactions raises the possibility that Cp-ppGalNAc-Ts may serve as targets for
      intervention in cryptosporidiosis.

PMID- 23954366
TI  - Strategies to construct null and conditional null Trypanosoma brucei mutants
      using Cre-recombinase and loxP.
AB  - We describe two gene-knockout (KO) strategies in Trypanosoma brucei using Cre
      recombinase and loxP sites. Due to the limited number of selection markers for T.
      brucei, it has been difficult to generate a mutant with two genes knocked out and
      impractical to simultaneously knockout more than two genes, deterring detailed
      studies of important cellular mechanisms. The first KO strategy described can
      overcome the marker problem by allowing continuous re-use of drug-resistance
      markers. The same KO vector can be used to make a conditional KO system, when a
      gene of interest is essential for cell viability. As a gene of interest is
      removed from its original chromosomal locus by the induction of Cre recombinase,
      deletion is complete and instantaneous. This makes it easier to identify primary
      effects rather than having secondary effects obscuring phenotypic assessment, as
      is often the case with RNAi silencing. 

PMID- 23954367
TI  - Long-term calorie restriction decreases metabolic cost of movement and prevents
      decrease of physical activity during aging in rhesus monkeys.
AB  - BACKGROUND: Short-term (<1 year) calorie restriction (CR) has been reported to
      decrease physical activity and metabolic rate in humans and non-human primate
      models; however, studies examining the very long-term (>10 year) effect of CR on
      these parameters are lacking. OBJECTIVE: The objective of this study was to
      examine metabolic and behavioral adaptations to long-term CR longitudinally in
      rhesus macaques. DESIGN: Eighteen (10 male, 8 female) control (C) and 24 (14
      male, 10 female) age matched CR rhesus monkeys between 19.6 and 31.9 years old
      were examined after 13 and 18 years of moderate adult-onset CR. Energy
      expenditure (EE) was examined by doubly labeled water (DLW; TEE) and respiratory
      chamber (24 h EE). Physical activity was assessed both by metabolic equivalent
      (MET) in a respiratory chamber and by an accelerometer. Metabolic cost of
      movements during 24 h was also calculated. Age and fat-free mass were included as
      covariates. RESULTS: Adjusted total and 24 h EE were not different between C and
      CR. Sleeping metabolic rate was significantly lower, and physical activity level
      was higher in CR than in C independent from the CR-induced changes in body
      composition. The duration of physical activity above 1.6 METs was significantly
      higher in CR than in C, and CR had significantly higher accelerometer activity
      counts than C. Metabolic cost of movements during 24 h was significantly lower in
      CR than in C. The accelerometer activity counts were significantly decreased
      after seven years in C animals, but not in CR animals. CONCLUSIONS: The results
      suggest that long-term CR decreases basal metabolic rate, but maintains higher
      physical activity with lower metabolic cost of movements compared with C.

PMID- 23954368
TI  - Aging compounds western diet-associated large artery endothelial dysfunction in
      mice: prevention by voluntary aerobic exercise.
AB  - We tested the hypothesis that aging will exacerbate the negative vascular
      consequences of exposure to a common physiological stressor, i.e., consumption of
      a "western" (high fat/high sucrose) diet (WD), by inducing superoxide-associated
      reductions in nitric oxide (NO) bioavailability, and that this would be prevented
      by voluntary aerobic exercise. Incremental stiffness and endothelium-dependent
      dilation (EDD) were measured in the carotid arteries of young (5.4+/-0.3 mo,
      N=20) and old (30.4+/-0.2 mo, N=19) male B6D2F1 mice fed normal chow (NC: 17%
      fat, 0% sucrose) or a western diet (40% fat, 19% sucrose) and housed in either
      standard cages or cages equipped with running wheels for 10-14 weeks. Incremental
      stiffness was higher in old NC (P<0.05) and both young (P<0.01) and old (P<0.01)
      WD fed mice compared with young NC mice, but WD did not further increase
      stiffness in the old mice. In cage control mice, maximal EDD was 17% lower in
      both NC fed old mice and young WD fed mice (P<0.05). Consumption of WD by old
      mice led to a further 20% reduction in maximal EDD (P<0.05). Incremental
      stiffness was 28% lower and maximal EDD was 38% greater in old WD fed mice with
      access to running wheels vs. old WD fed control mice (P<0.05) and not different
      from young NC fed controls. Wheel running also tended to improve maximal EDD
      (+9%, P=0.11), but not incremental stiffness in young WD fed mice. Ex vivo
      treatment with the superoxide scavenger TEMPOL and NO inhibitor l-NAME abolished
      these respective effects of age, WD and voluntary running on EDD. Ingestion of a
      WD induces similar degrees of endothelial dysfunction in old and young adult
      B6D2F1 mice, and these effects are mediated by a superoxide-dependent impairment
      of NO bioavailability. However, the combination of old age and WD, a common
      occurrence in our aging society, results in a marked, additive reduction in
      endothelial function. Importantly, regular voluntary aerobic exercise reduces
      arterial stiffness and protects against the adverse influence of WD on
      endothelial function in old animals by preventing superoxide suppression of NO.
      These findings may have important implications for arterial aging and the
      prevention of age-associated cardiovascular diseases.

PMID- 23954369
TI  - Usefulness of vessel-sealing devices combined with crush clamping method for
      hepatectomy: a retrospective cohort study.
AB  - BACKGROUND: Blood loss during resection of the hepatic parenchyma in hepatectomy
      can be minimized using vessel-sealing (VS) devices. Some sealing devices were
      retrospectively compared to evaluate the efficacy of each device for controlling
      blood loss, transection time and postoperative complications in hepatectomy as a
      cohort study. METHODS: Between 2005 and September 2012, hepatectomy was underwent
      in 150 patients using one of three types of LigaSureTM (Dolphin Tip Laparoscopic
      Instrument, Precise or Small Jaw) or the Harmonic Focus or Ace ultrasonic
      dissecting sealer. Results were compared to crush-clamping alone as the control
      method by the historical study (n = 81). RESULTS: Irrespective of the vessel
      sealing device used for underlying chronic hepatitis, blood loss, blood
      transfusion rate, operating time and transection time were significantly reduced
      in the VS group compared with controls (p < 0.05). Rates of postoperative bile
      leakage and intra-abdominal abscess formation were significantly lower in the VS
      group than in controls (p < 0.05). Comparing devices, LigaSure Small Jaw and
      Harmonic Focus showed lower blood loss, shorter transection time and reduced
      rates of post-hepatectomy complications, in turn resulting in shorter hospital
      stays (p < 0.05). Tendencies toward uncontrolled ascites and bile leakage were
      only concern with the use of Harmonic Focus. Satisfactory surgical results were
      achieved using the sealing device for laparoscopic hepatectomy. CONCLUSIONS: The
      use of energy sealing devices improves surgical results and avoids hepatectomy
      related complications. Adequate use of vessel sealers is necessary for safe and
      rapid completion of hepatic resection.

PMID- 23954370
TI  - pH-responsive and charge shielded cationic micelle of poly(L-histidine)-block
      short branched PEI for acidic cancer treatment.
AB  - To address cancer cell heterogeneity while endowing tumor specificity, the
      approach of charge shielding/deshielding was tested in vitro and in vivo with a
      paclitaxel loaded cationic micelle from a block copolymer of poly(L-histidine)
      (3.7kDa) and short branched polyethyleneimine (1.8 kDa). The cationic micelle
      surface was shielded by electrostatically complexing with a negatively charged
      mPEG (2 kDa)-block-polysulfadimethoxine (4 kDa) (mPEG-b-PSDM) at pH7.4.
      Unshielded micelle at pH7.4 and deshielded micelle at tumor extracellular pH were
      readily taken up by two wild types of human cancer cell lines, MCF-7 breast
      adenocarcinoma and SKOV-3 ovarian carcinoma, while the uptake of the shielded
      micelle at pH7.4 was minimal. The preliminary in vivo results from a mouse model
      xenografted with MCF-7 showed significant anticancer therapeutic efficacy and
      deep penetration of the micelle into tumor tissues after deshielding, supporting
      the unique pH-responsive mechanism to treat acidic cancer.

PMID- 23954371
TI  - Preface-tenth international nanomedicine and drug delivery symposium
      (NanoDDS'12).

PMID- 23954372
TI  - Stability of nanosuspensions in drug delivery.
AB  - Nanosuspensions are nanosized colloidal dispersion systems that are stabilized by
      surfactants and/or polymers. Because nanosizing results in the creation of new
      interfaces and in a positive Gibbs free energy change, nanosuspensions are
      thermodynamically unstable systems with a tendency toward agglomeration or
      crystal growth. Despite extensive research on nanosuspension technology,
      stability remains a limitation for pharmaceutical or industrial applications of
      nanosuspensions. Furthermore, the empirical relationship between stabilizer
      efficacy and nanosuspension stability has not been well characterized. This
      review focuses on the issue of nanosuspension stability in drug delivery to
      present the state of the art of nanosuspensions. Therefore, this review will
      discuss unstable suspensions, methods and guidelines for selecting and optimizing
      stabilizers, approaches for enhancing stability, and other factors that influence
      nanosuspension stability. This review could serve as a reference for the educated
      selection of a stabilizer for a specific drug candidate and the optimization of
      the operational parameters for nanosuspension formulation, rather than the
      currently practiced trial-and-error approach. 

PMID- 23954373
TI  - Dual PI3K/mTOR inhibitor NVP-BEZ235 sensitizes docetaxel in castration resistant
      prostate cancer.
AB  - PURPOSE: Effective therapeutic strategies that can achieve long-term improvement
      in patients with castration resistant prostate cancer are urgently needed. We
      recently reported that the activated PI3K/Akt/mTOR signaling pathway induced by
      docetaxel explains resistance to docetaxel in castration resistant prostate
      cancer. In this study we explored the efficacy of NVP-BEZ235, a dual PI3K and
      mTORC1/2 inhibitor, for docetaxel resistant castration resistant prostate cancer.
      MATERIALS AND METHODS: We used the 2 human castration resistant prostate cancer
      cell lines C4-2 and C4-2AT6. At our laboratory C4-2AT6 cells were established
      from C4-2 under androgen ablated treatment for 6 months. We investigated the
      efficacy of NVP-BEZ235 monotherapy and NVP-BEZ235 combined with docetaxel in
      vitro and in vivo. RESULTS: Increased phosphorylated Akt in C4-2AT6 cells was
      significantly inhibited by NVP-BEZ235 in a dose and time dependent manner. WST
      cell proliferation assay results in C4-2AT6 cells revealed that combined
      administration of NVP-BEZ235 and docetaxel had significant, synergistically
      greater cytotoxicity than NVP-BEZ235 or docetaxel monotherapy. Combined NVP
      BEZ235 (40 mg/kg) and docetaxel (4 mg/kg) in vivo in a castrated mouse xenograft
      model inhibited C4-2AT6 tumor growth to a greater degree than in the monotherapy
      groups. Also, NVP-BEZ235 showed significant efficacy with docetaxel at a low
      concentration in vivo, suggesting that NVP-BEZ235 effectively decreased
      resistance to docetaxel. CONCLUSIONS: Results suggest that inhibition of the
      PI3K/Akt/mTOR signaling pathway by NVP-BEZ235 can overcome docetaxel resistance
      in human castration resistant prostate cancer. Our findings provide a molecular
      basis for the clinical use of combined administration of NVP-BEZ235 and docetaxel
      in patients with castration resistant prostate cancer.

PMID- 23954374
TI  - Microsurgical rat varicocele model.
AB  - PURPOSE: A rat varicocele model using partial occlusion of the left renal vein
      was described previously. Reproducibility in creating this model has met with
      varied success. Alternate routes of testicular venous drainage may negate the
      effect of partial renal vein occlusion on varicocele creation. We hypothesized
      that varicocele induction would be more effective if microsurgical ligation of
      the gonadal venous drainage to the common iliac vein was combined with partial
      occlusion of the left renal vein. MATERIALS AND METHODS: We randomly assigned a
      total of 36 rats to 3 groups, including sham surgery, partial renal vein
      occlusion alone (the classic technique) and microsurgical ligation. Half of the
      rats in each group were evaluated at 5 and 12 weeks, respectively. We evaluated
      internal gonadal vein and spermatic cord diameter, testicular weight, cauda
      epididymal sperm concentration and motility and testicular histology using the
      Johnsen score as well as serum and intratesticular testosterone and
      dihydrotestosterone. RESULTS: Five weeks after varicocele creation the
      microsurgical ligation group had a larger spermatic cord diameter and lower
      Johnsen scores than rats in the classic technique and sham surgery groups. At 12
      weeks the microsurgical ligation group had a larger spermatic cord diameter,
      lower cauda epididymal sperm concentration, lower sperm motility and worse
      histology than the classic technique and sham surgery groups. There was no
      difference in serum androgen outcomes but the microsurgical ligation group had
      lower intratesticular androgens. CONCLUSIONS: Adding microsurgical ligation of
      testicular vein collaterals in the pelvis to partial renal vein occlusion appears
      to improve the effectiveness of creating a rat varicocele model.

PMID- 23954375
TI  - Decisions under risk in Parkinson's disease: preserved evaluation of probability
      and magnitude.
AB  - INTRODUCTION: Unmedicated Parkinson's disease patients tend to be risk-averse
      while dopaminergic treatment causes a tendency to take risks. While dopamine
      agonists may result in clinically apparent impulse control disorders, treatment
      with levodopa also causes shift in behaviour associated with an enhanced response
      to rewards. Two important determinants in decision-making are how subjects
      perceive the magnitude and probability of outcomes. Our objective was to
      determine if patients with Parkinson's disease on or off levodopa showed
      differences in their perception of value when making decisions under risk.
      METHODS: The Vancouver Gambling task presents subjects with a choice between one
      prospect with larger outcome and a second with higher probability. Eighteen age
      matched controls and eighteen patients with Parkinson's disease before and after
      levodopa were tested. In the Gain Phase subjects chose between one prospect with
      higher probability and another with larger reward to maximize their gains. In the
      Loss Phase, subjects played to minimize their losses. RESULTS: Patients with
      Parkinson's disease, on or off levodopa, were similar to controls when evaluating
      gains. However, in the Loss Phase before levodopa, they were more likely to avoid
      the prospect with lower probability but larger loss, as indicated by the steeper
      slope of their group psychometric function (t(24) = 2.21, p = 0.04). Modelling
      with prospect theory suggested that this was attributable to a 28% overestimation
      of the magnitude of loss, rather than an altered perception of its probability.
      CONCLUSION: While pre-medicated patients with Parkinson's disease show risk
      aversion for large losses, patients on levodopa have normal perception of
      magnitude and probability for both loss and gain. The finding of accurate and
      normally biased decisions under risk in medicated patients with PD is important
      because it indicates that, if there is indeed anomalous risk-seeking behaviour in
      such a cohort, it may derive from abnormalities in components of decision making
      that are separate from evaluations of size and probability.

PMID- 23954376
TI  - Reply to letter Re: Childhood adversity and cell-mediated immunity in young
      adulthood.

PMID- 23954377
TI  - Familial hemiplegic migraine mutations affect Na,K-ATPase domain interactions.
AB  - Familial hemiplegic migraine (FHM) is a monogenic variant of migraine with aura.
      One of the three known causative genes, ATP1A2, which encodes the alpha2 isoform
      of Na,K-ATPase, causes FHM type 2 (FHM2). Over 50 FHM2 mutations have been
      reported, but most have not been characterized functionally. Here we study the
      molecular mechanism of Na,K-ATPase alpha2 missense mutations. Mutants E700K and
      P786L inactivate or strongly reduce enzyme activity. Glutamic acid 700 is located
      in the phosphorylation (P) domain and the mutation most likely disrupts the salt
      bridge with Lysine 35, thereby destabilizing the interaction with the actuator
      (A) domain. Mutants G900R and E902K are present in the extracellular loop at the
      interface of the alpha and beta subunit. Both mutants likely hamper the
      interaction between these subunits and thereby decrease enzyme activity. Mutants
      E174K, R548C and R548H reduce the Na(+) and increase the K(+) affinity. Glutamic
      acid 174 is present in the A domain and might form a salt bridge with Lysine 432
      in the nucleotide binding (N) domain, whereas Arginine 548, which is located in
      the N domain, forms a salt bridge with Glutamine 219 in the A domain. In the
      catalytic cycle, the interactions of the A and N domains affect the K(+) and
      Na(+) affinities, as observed with these mutants. Functional consequences were
      not observed for ATP1A2 mutations found in two sporadic hemiplegic migraine cases
      (Y9N and R879Q) and in migraine without aura (R51H and C702Y). 

PMID- 23954378
TI  - Antigenicity and immunogenicity of a novel chimeric peptide antigen based on the
      P. vivax circumsporozoite protein.
AB  - BACKGROUND: Plasmodium vivax circumsporozoite (PvCS) protein is a major
      sporozoite surface antigen involved in parasite invasion of hepatocytes and is
      currently being considered as vaccine candidate. PvCS contains a dimorphic
      central repetitive fragment flanked by conserved regions that contain functional
      domains. METHODS: We have developed a chimeric 137-mer synthetic polypeptide
      (PvCS-NRC) that includes the conserved region I and region II-plus and the two
      natural repeat variants known as VK210 and VK247. The antigenicity of PvCS-NRC
      was tested using human sera from PNG and Colombia endemic areas and its
      immunogenicity was confirmed in mice with different genetic backgrounds, the
      polypeptide formulated either in Alum or GLA-SE adjuvants was assessed in inbred
      C3H, CB6F1 and outbred ICR mice, whereas a formulation in Montanide ISA51 was
      tested in C3H mice. RESULTS: Antigenicity studies indicated that the chimeric
      peptide is recognized by a high proportion (60-70%) of residents of malaria
      endemic areas. Peptides formulated with either GLA-SE or Montanide ISA51
      adjuvants induced stronger antibody responses as compared with the Alum
      formulation. Sera from immunized mice as well as antigen-specific affinity
      purified human IgG antibodies reacted with sporozoite preparations in
      immunofluorescence and Western blot assays, and displayed strong in vitro
      inhibition of sporozoite invasion (ISI) into hepatoma cells. CONCLUSIONS: The
      polypeptide was recognized at high prevalence when tested against naturally
      induced human antibodies and was able to induce significant immunogenicity in
      mice. Additionally, specific antibodies were able to recognize sporozoites and
      were able to block sporozoite invasion in vitro. Further evaluation of this
      chimeric protein construct in preclinical phase e.g. in Aotus monkeys in order to
      assess the humoral and cellular immune responses as well as protective efficacy
      against parasite challenge of the vaccine candidate must be conducted.

PMID- 23954379
TI  - Associations between health communication behaviors, neighborhood social capital,
      vaccine knowledge, and parents' H1N1 vaccination of their children.
AB  - During the H1N1 pandemic in 2009-10, the vaccination behavior of parents played a
      critical role in preventing and containing the spread of the disease and the
      subsequent health outcomes among children. Several studies have examined the
      relationship between parents' health communication behaviors and vaccinations for
      children in general. Little is known, however, about the link between parents'
      health communication behaviors and the vaccination of their children against the
      H1N1 virus, and their level of vaccine-related knowledge. We drew on a national
      survey among parents with at least one child less than 18 years of age (n=639) to
      investigate Parents' H1N1-related health communication behaviors including
      sources of information, media exposure, information-seeking behaviors, H1N1
      related knowledge, and neighborhood social capital, as well as the H1N1
      vaccination rates of their children. Findings showed that there is a significant
      association between the degree at which parents obtained H1N1 vaccination for
      their children and health communication variables: watching the national
      television news and actively seeking H1N1 information. And this association was
      moderated by the extent of the parents' H1N1-related knowledge. In addition, the
      parents' degree of neighborhood social capital mediated the association between
      H1N1 knowledge of the parents and H1N1 vaccination acceptance for their children.
      We found, compared to those with a low-level of neighborhood social capital,
      parents who have a high-level of neighborhood social capital are more likely to
      vaccinate their children. These findings suggest that it is necessary to design a
      strategic health communication campaign segmented by parent health communication
      behaviors. 

PMID- 23954380
TI  - Bactericidal antibody against a representative epidemiological meningococcal
      serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain
      coverage.
AB  - BACKGROUND: 4CMenB (Bexsero), a vaccine developed against invasive meningococcal
      disease caused by capsular group B strains (MenB), was recently licensed for use
      by the European Medicines Agency. Assessment of 4CMenB strain coverage in
      specific epidemiologic settings is of primary importance to predict vaccination
      impact on the burden of disease. The Meningococcal Antigen Typing System (MATS)
      was developed to predict 4CMenB strain coverage, using serum bactericidal
      antibody assay with human complement (hSBA) data from a diverse panel of strains
      not representative of any specific epidemiology. OBJECTIVE: To experimentally
      validate the accuracy of MATS-based predictions against strains representative of
      a specific epidemiologic setting. METHODS AND RESULTS: We used a stratified
      sampling method to identify a representative sample from all MenB disease
      isolates collected from England and Wales in 2007-2008, tested the strains in the
      hSBA assay with pooled sera from infant and adolescent vaccinees, and compared
      these results with MATS. MATS predictions and hSBA results were significantly
      associated (P=0.022). MATS predicted coverage of 70% (95% CI, 55-85%) was largely
      confirmed by 88% killing in the hSBA (95% CI, 72-95%). MATS had 78% accuracy and
      96% positive predictive value against hSBA. CONCLUSION: MATS is a conservative
      predictor of strain coverage by the 4CMenB vaccine in infants and adolescents.

PMID- 23954382
TI  - Attenuation of Theileria lestoquardi infected cells and immunization of sheep
      against malignant ovine theileriosis.
AB  - Malignant ovine theileriosis caused by Theileria lestoquardi is an economically
      important disease infecting small ruminants in the Sudan. The disease causes
      massive losses among sheep in many regions of Northern Sudan. The present studies
      were done to isolate lymphoblastoid cells infected with malignant ovine
      theileriosis and attenuate them by passage using culture media to develop and
      produce schizonts candidate vaccine, then test its efficacy and safety by
      exposing immunized lambs to field challenge in an area endemic with T.
      lestoquardi. In the present experiments we isolated and established an in vitro
      culture of T. lestoquardi infected lymphoblast cell line. Long-term culture of T.
      lestoquardi infected lymphoplastoid cells was shown to result in attenuation of
      their virulence and lambs inoculated with different doses of such cells at
      passage 105 exhibited very mild reactions with fever that lasted for 1-5 days and
      parasitaemia of <0.2%. The experimental lambs immunized with this candidate
      vaccine were immune and protected when exposed to field challenge in an area
      endemic of ovine theileriosis, while morbidity and mortality among non-immunized
      animals reached 76.9% and 46.15%, respectively, and they exhibited the clinical
      signs of malignant ovine theileriosis that included, high fever, loss of
      appetite, enlargement of lymph nodes, jaundice, loss of weight and death. The
      present study demonstrates the efficacy and the safety of this attenuated cell
      line as a live attenuated candidate vaccine.

PMID- 23954381
TI  - Antibody persistence and immunologic memory after sequential pneumococcal
      conjugate and polysaccharide vaccination in HIV-infected children on highly
      active antiretroviral therapy.
AB  - BACKGROUND: The capacity of pneumococcal vaccination to confer memory in HIV
      infected children is critical for durable protection. METHODS: HIV-infected
      children 2-<19 years administered two doses of pneumococcal conjugate vaccine
      (PCV7) and one dose of polysaccharide vaccine (PPV) on HAART were randomized 4-5
      years later to receive a PCV7 or PPV booster. Total and high avidity antibodies
      to serotypes 1 (PPV) and 6B and 14 (PCV7 and PPV) were determined by ELISA.
      Memory was defined as persistence of >= 0.5 mcg/mL of serotype-specific antibody
      on day 0 or change from <0.5 mcg/mL to >= 0.5 mcg/mL between day 0 and week 1,
      or, >= 4-fold antibody rise between day 0 and week 1. RESULTS: Prior to boosting,
      4-5 years after the previous PCV7-PCV7-PPV series, geometric mean concentrations
      (GMCs) were 0.46 mcg/mL (serotype 1), 1.31 mcg/mL (serotype 6B), and 1.47 mcg/mL
      (serotype 14), with concentrations >= 0.5 mcg/mL in 41% (serotype 1) to 82%
      (serotypes 6B and 14). Memory based on antibody concentration >= 0.5 mcg/mL
      before or 1 week after boosting with PCV7 or PPV was demonstrated in 42-61% for
      serotype 1 and 87-94% for serotypes 6B and 14, with lower rates based on day 0 to
      week 1 >= 4-fold antibody rise (serotype 1, 3-13%; serotype 6B, 13-31%; serotype
      14, 29-53%). Antibody concentrations post-boosting were greater following PCV7
      than PPV for serotypes 6B and 14. Ratios of highly avid to total antibody pre-
      and post-boosting were 0.5-0.8. Predictors of memory included higher CD4% (nadir
      before HAART and at P1024 and P1061s entry), CD19% (at P1024 and P1061s entry),
      and antibody response after the PCV7-PCV7-PPV primary series and lower viral load
      (at P1024 and P1061s entry) and age. CONCLUSIONS: Protective antibody
      concentrations, high avidity, and booster responses to PCV7 or PPV indicative of
      memory were present 4-5 years after PCV7-PCV7-PPV in HIV-infected children on
      HAART.

PMID- 23954384
TI  - SIV antigen-specific effects on immune responses induced by vaccination with DNA
      electroporation and plasmid IL-12.
AB  - Molecular adjuvants are important for augmenting or modulating immune responses
      induced by DNA vaccination. Promising results have been obtained using IL-12
      expression plasmids in a variety of disease models including the SIV model of HIV
      infection. We used a mouse model to evaluate plasmid IL-12 (pIL-12) in a DNA
      prime, recombinant adenovirus serotype 5 (rAd5) boost regimen specifically to
      evaluate the effect of IL-12 expression on cellular and humoral immunity induced
      against both SIVmac239 Gag and Env antigens. Priming with electroporated (EP)
      DNA+pIL-12 resulted in a 2-4-fold enhanced frequency of Gag-specific CD4 T cells
      which was maintained through the end of the study irrespective of the pIL-12
      dose, while memory Env-specific CD4+T cells were maintained only at the low dose
      of pIL-12. There was little positive effect of pIL-12 on the humoral response to
      Env, and in fact, high dose pIL-12 dramatically reduced SIV Env-specific IgG.
      Additionally, both doses of pIL-12 diminished the frequency of CD8 T-cells after
      DNA prime, although a rAd5 boost recovered CD8 responses regardless of the pIL-12
      dose. In this prime-boost regimen, we have shown that a high dose pIL-12 can
      systemically reduce Env-specific humoral responses and CD4T cell frequency, but
      not Gag-specific CD4+ T cells. These data indicate that it is important to
      independently characterize individual SIV or HIV antigen immunogenicity in multi
      antigenic vaccines as a function of adjuvant dose. 

PMID- 23954385
TI  - The biomechanical variables involved in the aetiology of iliotibial band syndrome
      in distance runners - A systematic review of the literature.
AB  - The aim of this literature review was to identify the biomechanical variables
      involved in the aetiology of iliotibial band syndrome (ITBS) in distance runners.
      An electronic search was conducted using the terms "iliotibial band" and
      "iliotibial tract". The results showed that runners with a history of ITBS appear
      to display decreased rear foot eversion, tibial internal rotation and hip
      adduction angles at heel strike while having greater maximum internal rotation
      angles at the knee and decreased total abduction and adduction range of motion at
      the hip during stance phase. They further appear to experience greater invertor
      moments at their feet, decreased abduction and flexion velocities at their hips
      and to reach maximum hip flexion angles earlier than healthy controls. Maximum
      normalised braking forces seem to be decreased in these athletes. The literature
      is inconclusive with regards to muscle strength deficits in runners with a
      history of ITBS. Prospective research suggested that greater internal rotation at
      the knee joint and increased adduction angles of the hip may play a role in the
      aetiology of ITBS and that the strain rate in the iliotibial bands of these
      runners may be increased compared to healthy controls. A clear biomechanical
      cause for ITBS could not be devised due to the lack of prospective research. 

PMID- 23954383
TI  - The influence of antigen targeting to sub-cellular compartments on the anti
      allergic potential of a DNA vaccine.
AB  - BACKGROUND: Gene vaccines offer attractive rationales for prophylactic as well as
      therapeutic treatments of type I allergies. DNA and mRNA vaccines have been shown
      to prevent from allergic sensitization and to counterbalance established allergic
      immune reactions. Recent advances in gene vaccine manipulation offer additional
      opportunities for modulation of T helper cell profiles by specific targeting of
      cellular compartments. METHODS: DNA vaccines encoding the major birch pollen
      allergen Bet v 1.0101 were equipped with different leader sequences to shuttle
      the antigen to lysosomes (LIMP-II), to trigger cellular secretion (hTPA), or to
      induce proteasomal degradation via forced ubiquitination (ubi). Mice were pre
      vaccinated with these constructs and the protective efficacy was tested by
      subcutaneous Th2-promoting challenges, followed by allergen inhalation. IgG
      antibody subclass distribution and allergen-specific IgE as well as cytokine
      profiles from re-stimulated splenocytes and from BALFs were assessed. The
      cellular composition of BALFs, and lung resistance and compliance were
      determined. RESULTS: Immunization with all targeting variants protected from
      allergic sensitization, i.e. IgE induction, airway hyperresponsiveness, lung
      inflammation, and systemic and local Th2 cytokine expression. Surprisingly,
      protection did not clearly correlate with the induction of a systemic Th1
      cytokine profile, but rather with proliferating CD4+ CD25+ FoxP3+ T regulatory
      cells in splenocyte cultures. Targeting the allergen to proteasomal or lysosomal
      degradation severely down-regulated antibody induction after vaccination, while T
      cell responses remained unaffected. Although secretion of antigen promoted the
      highest numbers of Th1 cells, this vaccine type was the least efficient in
      suppressing the establishment of an allergic immune response. CONCLUSION: This
      comparative analysis highlights the modulatory effect of antigen targeting on the
      resulting immune response, with a special emphasis on prophylactic anti-allergy
      DNA vaccination. Targeting the antigen to proteasomal or lysosomal degradation
      reduces the availability of native allergen, thereby rendering the vaccine
      hypoallergenic without compromising efficacy, an important feature for a
      therapeutic setting.

PMID- 23954386
TI  - Chronic ankle instability affects learning rate during repeated proprioception
      testing.
AB  - OBJECTIVES: 1. To determine whether individuals with chronic ankle instability
      (CAI) have lower proprioception sensitivity scores from a test on the Active
      Movement Extent Discrimination Apparatus (AMEDA). 2. To determine whether
      individuals with CAI can improve proprioception sensitivity scores with repeated
      active movement testing using the AMEDA. 3. To assess the test-retest reliability
      of the AMEDA. DESIGN: A cohort study comparing those with CAI or healthy ankles.
      SETTING: University clinical laboratory. PARTICIPANTS: 61 healthy university
      students, 36 with CAI, 25 with stable ankles. MAIN OUTCOME MEASURES: A 2-way
      ANOVA was conducted to compare performance of CAI and stable ankle groups, over 3
      test repetitions on the AMEDA. The reliability intra-class correlation
      coefficient (ICC) was obtained for test repetitions. RESULTS: The scores improved
      in both groups when the AMEDA test was repeated (p = <0.001). The rates of
      improvement in proprioception test scores differed, with the CAI group showing a
      slower learning rate than the stable ankle group (p = 0.047). The ICC for the
      whole group across the three trials was 0.80 (95% CI = 0.69 to 0.87, p = <0.001).
      CONCLUSIONS: CAI participants improve their proprioception scores more slowly
      upon repeated AMEDA testing, suggesting differences in learning strategies.

PMID- 23954387
TI  - Intercoat (Oxiplex/AP gel) for preventing intrauterine adhesions after operative
      hysteroscopy for suspected retained products of conception: double-blind,
      prospective, randomized pilot study.
AB  - STUDY OBJECTIVE: To evaluate the safety and effectiveness of Oxiplex/AP gel
      (Intercoat) in reducing intrauterine adhesion formation after hysteroscopic
      treatment because of retained products of conception (RPOC). DESIGN: Prospective
      double-blind, randomized, controlled pilot study (Canadian Task Force
      classification I). SETTING: Tertiary medical center. PATIENTS: All women who
      underwent hysteroscopic treatment because of RPOC at our institution between
      September 2009 and June 2012 were invited to participate. After operative
      hysteroscopy, participants were randomized to either have their uterine cavity
      filled with Oxiplex/AP gel (study group, n = 26) or not (control group, n = 26).
      INTERVENTIONS: Diagnostic office hysteroscopy to assess for adhesion formation
      was performed after 6 to 8 weeks. Findings were graded according to the American
      Fertility Society classification. Rates of subsequent pregnancy in the 2 groups
      were assessed. MEASUREMENTS AND MAIN RESULTS: Intraoperative complication rates
      were similar between the 2 groups. There were no postoperative complications
      after Oxiplex/AP gel application. Moderate to severe adhesions developed in 1
      woman (4%) in the study group and 3 (14%) in the control group (p = .80). During
      follow-up of 20 months (range, 2-33 months), 7 women (27%) in the treatment group
      conceived, compared with 3 (14%) in the control group (p = .50). CONCLUSION:
      Intrauterine application of Oxiplex/AP gel after hysteroscopic removal of RPOC is
      safe. In this small sample, the difference in the rate of intrauterine adhesions
      was not statistically significant. A larger study would enable further
      establishment of the safety and efficacy of use of this gel.

PMID- 23954388
TI  - Application of termite nest for adsorption of Cr(VI).
AB  - This work proposes the use of tree termite nest as an adsorbent for the
      reduction/removal of Cr(VI) present in aqueous solution. In laboratory
      experiments, adsorption of Cr(VI) was sensitive to pH in the range investigated
      (2-5), with maximum adsorption capacity achieved at pH 2 (3.70 +/- 0.04 mg g(-1),
      representing 93.2% removal of Cr). The termite nest was characterized by off-line
      pyrolysis GC/MS (py-GC/MS), infrared spectroscopy (FTIR), and electron
      paramagnetic resonance spectroscopy (EPR). Pyrolysis of the adsorbent produced a
      complex mixture of aromatic compounds, including the guaiacyl and syringilic
      derivatives that are characteristic of lignocellulosic materials. Infrared
      spectroscopy revealed deprotonation of the carboxylic acid group of the biomass
      with increasing pH, which was associated with a decrease in the capacity for
      adsorption of Cr(VI). The EPR g-factor for the termite nest samples varied
      between 2.0037 and 2.0038, indicating the presence of organic free radicals that
      were responsible for the redox reaction. A second line with g-factor values of
      1.9790, only observed for the samples after contact with Cr(VI) solutions at
      different pH values, was assigned to Cr(III)-Cr(III) exchange coupled pairs,
      which explained the capacity of the adsorbent to retain a large portion of the
      Cr(III) ions produced after reduction of Cr(VI) to Cr(III). Fixed-bed column
      experiments showed that the termite nest had a maximum adsorption capacity of
      18.60 mg Cr g(-1), an adsorption efficiency varying between 60.8 and 97.4%, and a
      desorption efficiency varying between 54.5 and 91.4%, for three successive
      cycles. The adsorbent presented excellent performance in the removal of chromium
      under acidic conditions, with the advantage that it could be regenerated and
      reused. 

PMID- 23954389
TI  - Vegetation moderates impacts of tourism usage on bird communities along roads and
      hiking trails.
AB  - Bird communities inhabiting ecosystems adjacent to recreational tracks may be
      adversely affected by disturbance from passing tourism traffic, vehicle-related
      mortality, habitat alteration and modified biotic relationships such as the
      increase of strong competitors. This study investigated the effects of tourist
      usage of roads vs. hiking trails on bird communities in gorges of the Flinders
      Ranges, a popular South Australian tourist destination in the arid-lands. High
      tourist usage along roads decreased the individual abundance and species richness
      of birds relative to low usage trails. The decrease in species richness, though
      less pronounced, also occurred at high-usage sites along trails. Changes in the
      species response to recreational disturbance/impacts varied depending on the
      ecology of the species. Bigger, more competitive birds with a generalist diet
      were overrepresented at high-usage sites along roads and trails. Species using
      microhabitats in lower vegetation layers were more sensitive. However, structural
      and floristic complexity of vegetation was a more important factor influencing
      bird abundance than tourist usage. Sites with a better developed shrub and tree
      layer sustained higher species abundance and richer communities. Importantly,
      vegetation qualities moderated the negative effect of high usage on the
      individual abundance of birds along roads, to the extent that such an effect was
      absent at sites with the best developed shrub and tree layer. To protect avifauna
      along recreational tracks in arid-lands gorges, we recommend the closure of some
      gorges or sections for vehicle or any access. Further, open space particularly
      for camping needs to be minimized as it creates areas of high tourist usage with
      modified habitat that provides birds with little buffer from disturbance. 

PMID- 23954390
TI  - Co-occurrence of multiple sclerosis and cancer in a BRCA1 positive family.
AB  - Multiple sclerosis is not known to be a risk factor for subsequent development of
      cancer. Recently, a multiple sclerosis locus was mapped adjacent to BRCA1 gene.
      We present a familial case affected by multiple sclerosis and cancer. We
      identified a c.5266dupC (5382insC) frameshift mutation in a 33-year-old woman
      with breast cancer, multiple malignant melanomas and multiple sclerosis. The
      patient's family history shows further cases of multiple sclerosis in BRCA1
      mutation carriers. Therefore the presented family may carry a monogenic
      predisposition for multiple sclerosis nearby to BRCA1. 

PMID- 23954391
TI  - Association between tumor diameter and lymphovascular space invasion among women
      with early-stage endometrial cancer.
AB  - OBJECTIVE: To investigate the association between tumor diameter and intratumoral
      risk factors that might predict the need for full surgical staging among women
      with endometrial cancer (EC). METHODS: Data from patients with early-stage EC
      treated at the Istituto Nazionale dei Tumori, Milan, Italy, between January 2004
      and December 2012 were retrospectively analyzed. Associations between tumor
      diameter and tumor grade, myometrial invasion, risk group, lymphovascular space
      invasion (LVSI), and lower uterine segment (LUS) involvement were assessed by
      bivariate and multivariate analysis. RESULTS: In total, 181 patients met the
      inclusion criteria. The tumor diameter was 2cm or less in 110 women (60%). chi(2)
      analysis showed that tumor grading, myometrial invasion, risk group, and LVSI
      were significantly associated with tumor size (P<0.001), whereas LUS involvement
      was marginally associated (P=0.051). By multivariate analysis, LVSI and
      myometrial invasion had an independent association with tumor size greater than
      2cm (P<0.018). CONCLUSION: Tumor size greater than 2cm was significantly and
      independently associated with LVSI and myometrial invasion among patients with
      early-stage EC. Given the difficulty of obtaining reliable LVSI data from frozen
      sections, tumor size might be used as a surrogate at the time of surgery to
      provide additional information to triage patients for full surgical staging.

PMID- 23954392
TI  - MAPIT: development of a web-based intervention targeting substance abuse
      treatment in the criminal justice system.
AB  - Although drug and alcohol treatment are common requirements in the U.S. criminal
      justice system, only a minority of clients actually initiate treatment. This
      paper describes a two-session, web-based intervention to increase motivation for
      substance abuse treatment among clients using illicit substances. MAPIT
      (Motivational Assessment Program to Initiate Treatment) integrates the extended
      parallel process model, motivational interviewing, and social cognitive theory.
      The first session (completed near the start of probation) targets motivation to
      complete probation, to make changes in substance use (including treatment
      initiation), and to obtain HIV testing and care. The second session (completed
      approximately 30days after session 1) focuses on goal setting, coping strategies,
      and social support. Both sessions can generate emails or mobile texts to remind
      clients of their goals. MAPIT uses theory-based algorithms and a text-to-speech
      engine to deliver custom feedback and suggestions. In an initial test,
      participants indicated that the program was respectful, easy to use, and would be
      helpful in making changes in substance use. MAPIT is being tested in a randomized
      trial in two large U.S. probation agencies. MAPIT addresses the difficulties of
      many probation agencies to maximize client involvement in treatment, in a way
      that is cost effective and compatible with the existing service delivery system. 

PMID- 23954393
TI  - Sexual experience and testosterone during adolescence alter adult neuronal
      morphology and behavior.
AB  - Steroid hormones released immediately before and after birth provoke sexual
      differentiation of neural circuits. Further, steroid hormones secreted during
      adolescence also exert long lasting effects on the nervous system. Hormones
      secreted during development may act through two distinct pathways: (1) hormones
      can directly affect neuron and synapse elimination and (2) endocrine changes in
      the nervous system may occur secondary to changes in social behaviors. Therefore,
      a critical period for organization of the nervous system by steroid hormones
      during adolescence may also be a sensitive period for the effects of social
      experience. The overall goal of this experiment was to determine whether the
      opportunity to mate with a sexually receptive female during this adolescent
      critical period would have enduring effects on behavior and neuronal morphology
      into adulthood. A second question was to determine the extent to which
      testosterone mediated the effects of these social interactions on adult outcomes.
      Compared to sexually inexperienced hamsters and those that experienced sex for
      the first time in adulthood, hamsters that experienced adolescent sexual
      experience displayed increased anxiety- and depressive-like behavioral responses.
      Adolescent sexual experiences decreased the complexity and length of dendrites on
      prefrontal cortical neurons and increased the expression of the pro-inflammatory
      cytokine interleukin 1beta (IL-1beta) in the PFC. In a second experiment,
      administration of testosterone during the adolescent period largely recapitulated
      the effects of adolescent sexual experience. These data support the overall
      hypothesis that a sensitive period extends into adolescence and that salient
      social stimuli during this time can significantly and persistently alter adult
      phenotype. 

PMID- 23954394
TI  - Amelioratory effects of testosterone treatment on cognitive performance deficits
      induced by soluble Abeta1-42 oligomers injected into the hippocampus.
AB  - This study was undertaken to investigate the protective effects and potential
      mechanism of testosterone (T) on cognitive performance in adult male rats given
      bilateral intrahippocampal injections of beta amyloid 1-42 oligomers (Abeta1-42)
      combined with gonadectomy (Abeta+GDX). A series of experiments were designed to
      verify the optimal administration time and dose of T and to explore its potential
      protective mechanisms on spatial ability in Abeta+GDX rats in the Morris water
      maze test. Abeta1-42 was injected only once two weeks before testing, while T and
      the androgen receptor (AR) antagonist flutamide (F) were administered daily
      beginning 2 days before and throughout the 6 days of testing. The Abeta1-42
      injection and GDX individually impaired cognitive performance, and the
      combination of these treatments was additive, leading to even greater impairment.
      The serum T level peaked at 48 h after administration. T doses ranging from 0.25
      to 1.00 mg corresponding to serum T levels of 4.5-21.35 ng/ml improved the
      spatial ability. Animals administered 0.75 mg of T corresponding to the serum T
      level of 15.2 ng/ml had the most significantly improved behavioral performances.
      However, higher T doses of 1.50 and 2.00 mg resulting in serum T levels of 34.8
      and 45 ng/ml, respectively, impaired the behavioral performances. F had no effect
      on the serum T level and spatial ability, but it blocked the activational effect
      of T. These findings indicate that the effect of T on behavioral performances is
      partly mediated through ARs.

PMID- 23954395
TI  - Telomere length: a marker of disease susceptibility?

PMID- 23954396
TI  - Phase II study of lapatinib in combination with vinorelbine in patients with HER2
      positive recurrent or metastatic breast cancer: a multicentric Turkish Oncology
      Group (TOG) trial.
AB  - BACKGROUND: The aim of this explorative phase II study was to evaluate the
      activity and safety of lapatinib in combination with intravenous vinorelbine in
      women with HER2 positive metastatic or recurrent breast cancer. METHODS: Twenty
      nine patients were enrolled. The primary objectives were response and clinical
      benefit (CB) rates, secondary objectives were toxicity, response duration and
      progression free survival. Patients received 1250 mg oral lapatinib continuously
      once daily and intravenous vinorelbine 20-25 mg/m(2) on days 1 and 8, every 3
      weeks. RESULTS: Although 25 patients were evaluable for response, according to
      intend to treat analysis of 28 patients; 14% had confirmed partial response (PR)
      and 36% had stable disease more than 24 weeks with a CB rate of 50%. Sixty four
      percent of the patients suffered from grade 3-4 hematologic and 18% from grade 3
      extra-hematologic toxicities. CONCLUSION: The results of this trial provide
      evidence to further investigate the potential of this combination for patients
      unsuitable for trastuzumab or who become refractory to trastuzumab.

PMID- 23954397
TI  - RAGE and TLRs: relatives, friends or neighbours?
AB  - The innate immune system forms the first line of protection against infectious
      and non-infectious tissue injury. Cells of the innate immune system detect
      pathogen-associated molecular patterns or endogenous molecules released as a
      result of tissue injury or inflammation through various innate immune receptors,
      collectively termed pattern-recognition receptors. Members of the Toll-like
      receptor (TLR) family of pattern-recognition receptors have well established
      roles in the host immune response to infection, while the receptor for advanced
      glycation end products (RAGE) is a pattern-recognition receptor predominantly
      involved in the recognition of endogenous molecules released in the context of
      infection, physiological stress or chronic inflammation. RAGE and TLRs share
      common ligands and signaling pathways, and accumulating evidence points towards
      their co-operative interaction in the host immune response. At present however,
      little is known about the mechanisms that result in TLR versus RAGE signalling or
      RAGE-TLR cross-talk in response to their shared ligands. Here we review what is
      known in relation to the physicochemical basis of ligand interactions between
      TLRs and RAGE, focusing on three shared ligands of these receptors: HMGB1,
      S100A8/A9 and LPS. Our aim is to discuss what is known about differential ligand
      interactions with RAGE and TLRs and to highlight important areas for further
      investigation so that we may better understand the role of these receptors and
      their relationship in host defense. 

PMID- 23954398
TI  - Characterization of the interaction between collectin 11 (CL-11, CL-K1) and
      nucleic acids.
AB  - Collectins are a group of innate immune proteins that contain collagen-like
      regions and globular C-type lectin domains. Via the lectin domains, collectins
      recognize and bind to various microbial carbohydrate patterns. Collectin 11 (CL
      11) exists in complex with the complement activating MBL-associated proteases,
      MASPs. In the present work, we characterize the interaction between CL-11 and
      DNA, and show that CL-11 binds to DNA from a variety of origins in a calcium
      independent manner. CL-11 binds also to apoptotic cells presenting extracellular
      DNA on their surface. The binding to DNA is sensitive to changes in ionic
      strength and pH. Competition studies show that CL-11 binds to nucleic acids and
      carbohydrates via separate binding-sites and oligomericity appears crucial for
      binding activity. Combined interaction with DNA and mannan strongly increases
      binding avidity. By surface plasmon resonance we estimate the dissociation
      constant for the binding between CL-11 and double stranded DNA oligonucleotides
      to K(D)=9-20 nM. In an in vitro assay we find that CL-11 binds to DNA coated
      surfaces, which leads to C4b deposition via MASP-2. We propose that CL-11, e.g.
      via complement, may play a role in response to particles and surfaces presenting
      extracellular DNA, such as apopototic cells, neutrophil extracellular traps and
      biofilms.

PMID- 23954400
TI  - Parp1 deficient mice are protected from streptozotocin-induced diabetes but not
      caerulein-induced pancreatitis, independent of the induction of Reg family genes.
AB  - Poly(ADP-ribose) polymerase (Parp) 1 is a key regulator of cell death, its
      inhibition prevented streptozotocin-induced diabetes and attenuated caerulein
      induced acute pancreatitis. Reg family proteins are significantly induced by
      Parp1 inhibitor, experimental diabetes and/or acute pancreatitis. We propose that
      Reg proteins are involved in the protection of pancreatic cells by Parp1
      inhibition. To test this possibility, Parp1-/- and wild-type mice were injected
      with streptozotocin to induce diabetes. Separately, acute pancreatitis was
      induced with repeated injections of caerulein. Upon streptozotocin
      administration, Parp1-/- mice displayed much decreased hyperglycemia and
      preserved serum insulin level. The treatment induced similar levels of Reg1, -2, 
      3alpha and -3beta genes in the pancreas of both wild-type and Parp1-/- mice,
      suggesting that the upregulation of Reg family genes during streptozotocin
      induced diabetes was independent of Parp1 ablation. In caerulein-induced
      pancreatitis, unlike being reported, Parp1 knockout caused no relief on the
      severity of pancreatitis; the upregulation of pancreatic Reg1, -2, -3alpha and 
      3beta genes upon caerulein was unaffected by Parp1 deletion. Our results
      reconfirmed the protective effect of Parp1 gene deletion on islet beta-cells but
      questioned its effect on the acinar cells. In either case, the significant
      induction of Reg family genes seemed independent of Parp1-mediated cell death. 

PMID- 23954399
TI  - The zinc finger transcription factor ZXDC activates CCL2 gene expression by
      opposing BCL6-mediated repression.
AB  - The zinc finger X-linked duplicated (ZXD) family of transcription factors has
      been implicated in regulating transcription of major histocompatibility complex
      class II genes in antigen presenting cells; roles beyond this function are not
      yet known. The expression of one gene in this family, ZXD family zinc finger C
      (ZXDC), is enriched in myeloid lineages and therefore we hypothesized that ZXDC
      may regulate myeloid-specific gene expression. Here we demonstrate that ZXDC
      regulates genes involved in myeloid cell differentiation and inflammation.
      Overexpression of the larger isoform of ZXDC, ZXDC1, activates expression of
      monocyte-specific markers of differentiation and synergizes with phorbol 12
      myristate 13-acetate (which causes differentiation) in the human leukemic
      monoblast cell line U937. To identify additional gene targets of ZXDC1, we
      performed gene expression profiling which revealed multiple inflammatory gene
      clusters regulated by ZXDC1. Using a combination of approaches we show that ZXDC1
      activates transcription of a gene within one of the regulated clusters, chemokine
      (C-C motif) ligand 2 (CCL2; monocyte chemoattractant protein 1; MCP1) via a
      previously defined distal regulatory element. Further, ZXDC1-dependent up
      regulation of the gene involves eviction of the transcriptional repressor B-cell
      CLL/lymphoma 6 (BCL6), a factor known to be important in resolving inflammatory
      responses, from this region of the promoter. Collectively, our data show that
      ZXDC1 is a regulator in the process of myeloid function and that ZXDC1 is
      responsible for Ccl2 gene de-repression by BCL6. 

PMID- 23954401
TI  - Building functional materials for health care and pharmacy from microfluidic
      principles and Flow Focusing.
AB  - In this review, we aim at establishing a relationship between the fundamentals of
      the microfluidics technologies used in the Pharmacy field, and the achievements
      accomplished by those technologies. We describe the main methods for
      manufacturing micrometer drops, bubbles, and capsules, as well as the
      corresponding underlying physical mechanisms. In this regard, the review is
      intended to show non-specialist readers the dynamical processes which determine
      the success of microfluidics techniques. Flow focusing (FF) is a droplet-based
      method widely used to produce different types of fluid entities on a continuous
      basis by applying an extensional co-flow. We take this technique as an example to
      illustrate how microfluidics technologies for drug delivery are progressing from
      a deep understanding of the physics of fluids involved. Specifically, we describe
      the limitations of FF, and review novel methods which enhance its stability and
      robustness. In the last part of this paper, we review some of the accomplishments
      of microfluidics when it comes to drug manufacturing and delivery. Special
      attention is paid to the production of the microencapsulated form because this
      fluidic structure gathers the main functionalities sought for in Pharmacy. We
      also show how FF has been adapted to satisfy an ample variety of pharmaceutical
      requirements to date. 

PMID- 23954403
TI  - Comparing the sustainability of different action policy possibilities:
      application to the issue of both household survival and forest preservation in
      the corridor of Fianarantsoa.
AB  - A sustainability issue for the rain forest in the corridor of Fianarantsoa
      (Madagascar) is to preserve the forest while ensuring the development of the
      local population. The aim of this paper is to determine whether the current
      situation is sustainable or not according to different action policy
      possibilities. We propose a general procedure based on viability analysis:
      Translation of sustainability issues into constraints on the system state;
      elaboration of a mathematical model of system evolution rules in the form of
      controlled dynamical system; computations of the viability kernels according to
      different action policy possibilities. Among control variables, we focus on
      monetary transfer. Without monetary transfer, we show that the current situation
      of the rain forest corridor is not sustainable in our mathematical modeling
      framework. We then estimate the minimal maximal amount per year necessary to make
      the current situation sustainable. 

PMID- 23954402
TI  - Carbon nanotubes for delivery of small molecule drugs.
AB  - In the realm of drug delivery, carbon nanotubes (CNTs) have gained tremendous
      attention as promising nanocarriers, owing to their distinct characteristics,
      such as high surface area, enhanced cellular uptake and the possibility to be
      easily conjugated with many therapeutics, including both small molecules and
      biologics, displaying superior efficacy, enhanced specificity and diminished side
      effects. While most CNT-based drug delivery system (DDS) had been engineered to
      combat cancers, there are also emerging reports that employ CNTs as either the
      main carrier or adjunct material for the delivery of various non-anticancer
      drugs. In this review, the delivery of small molecule drugs is expounded, with
      special attention paid to the current progress of in vitro and in vivo research
      involving CNT-based DDSs, before finally concluding with some consideration on
      inevitable complications that hamper successful disease intervention with CNTs. 

PMID- 23954405
TI  - Early social instability affects plasma testosterone during adolescence but does
      not alter reproductive capacity or measures of stress later in life.
AB  - The social environment plays an important role in modulating processes of the
      hormonal and behavioural profile of an animal in a variety of group-living
      species. In wild cavies for instance, unstable social environmental conditions
      during pregnancy and lactation lead to an infantilised biobehavioural profile of
      the male offspring. In the present study, the influence of the social environment
      during pregnancy and lactation on the male wild cavy offsprings' plasma
      testosterone development, reproductive capacity and stress system activity was
      investigated. To this purpose, 12 sons whose mothers had lived in an unstable
      social environment during pregnancy and lactation were compared with 12 sons
      whose mothers had lived in a stable social environment during the same time.
      Plasma testosterone (T) and plasma cortisol (C) concentrations were determined
      from days 20 to 107 of age. Adrenal tyrosine hydroxylase (TH) activity and
      different parameters of reproductive capacity (weights of testes, epididymides
      and accessory sex glands, cellular composition of the testes, DNA fragmentation
      indices and sperm motility parameters) were analysed at day 107 of age. TH
      activity and plasma C were unaffected by different social environmental
      conditions early in life. The developmental time course of T concentrations,
      however, was significantly different: Sons whose mothers had lived in an unstable
      social environment during pregnancy and lactation showed a delayed increase in T
      concentrations around adolescence compared to controls. In contrast, no
      reproduction-related parameters measured within this study differed significantly
      between the two groups. Thus, early social instability affects plasma
      testosterone development during adolescence in a significant way but does not
      alter reproductive capacity or measures of stress later in life. 

PMID- 23954406
TI  - Effects of sleep restriction on the human plasma metabolome.
AB  - This study examined the effects of recurrent sleep restriction on the plasma
      metabolome of adults with familial risk of type 2 diabetes. Eleven healthy adults
      (6M/5F; mean [SD] age: 26 [3]years; BMI 23.5 [2.3]kg/m(2)) with parental history
      of type 2 diabetes participated in a two-condition, two-period randomized
      crossover study at the Clinical Resource Center at an academic hospital. Each
      participant completed two 8-night inpatient sessions with restricted (5.5-h time
      in-bed) vs. adequate (8.5-h time-in-bed) sleep opportunity while daily food
      intake and physical activity were carefully controlled. A combination of two
      UHPLC/MS/MS platforms and one GC/MS platform was used to measure 362 biochemicals
      in fasting plasma samples collected from study participants the morning after
      each 8-night sleep treatment. Relative concentrations of 12 amino acids and
      related metabolites were increased when sleep was curtailed. Sleep restriction
      also induced elevations in several fatty acid, bile acid, steroid hormone, and
      tricarboxylic acid cycle intermediates. In contrast, circulating levels of
      glucose, some monosaccharides, gluconate, and five-carbon sugar alcohols tended
      to decline when sleep was reduced. Recurrent sleep curtailment affected multiple
      pathways of intermediary metabolism in adults at risk for type 2 diabetes. An
      elevation in plasma amino acids and related biochemicals was the most pronounced
      metabolic signature seen in response to 8 nights of sleep restriction. 

PMID- 23954404
TI  - High fat diet induced obesity alters ovarian phosphatidylinositol-3 kinase
      signaling gene expression.
AB  - Insulin regulates ovarian phosphatidylinositol-3-kinase (PI3 K) signaling,
      important for primordial follicle viability and growth activation. This study
      investigated diet-induced obesity impacts on: (1) insulin receptor (Insr) and
      insulin receptor substrate 1 (Irs1); (2) PI3K components (Kit ligand (Kitlg), kit
      (c-Kit), protein kinase B alpha (Akt1) and forkhead transcription factor
      subfamily 3 (Foxo3a)); (3) xenobiotic biotransformation (microsomal epoxide
      hydrolase (Ephx1), Cytochrome P450 isoform 2E1 (Cyp2e1), Glutathione S
      transferase (Gst) isoforms mu (Gstm) and pi (Gstp)) and (4) microRNA's 184, 205,
      103 and 21 gene expression. INSR, GSTM and GSTP protein levels were also
      measured. Obese mouse ovaries had decreased Irs1, Foxo3a, Cyp2e1, MiR-103, and
      MiR-21 but increased Kitlg, Akt1, and miR-184 levels relative to lean
      littermates. These results support that diet-induced obesity potentially impairs
      ovarian function through aberrant gene expression. 

PMID- 23954407
TI  - Chronic restricted access to 10% sucrose solution in adolescent and young adult
      rats impairs spatial memory and alters sensitivity to outcome devaluation.
AB  - Although increasing consumption of sugar drinks is recognized as a significant
      public health concern, little is known about (a) the cognitive effects resulting
      from sucrose consumption; and (b) whether the long-term effects of sucrose
      consumption are more pronounced for adolescents. This experiment directly
      compared performance on a task of spatial learning and memory (the Morris Water
      Maze) and sensitivity to outcome devaluation following 28 days of 2-h/day access
      to a 10% sucrose solution in adolescent and young-adult Wistar rats. Sucrose
      groups developed elevated fasting blood glucose levels after the diet
      intervention, despite drawing <15% of calories from sucrose and gaining no more
      weight than controls. In subsequent behavioral testing, sucrose groups were
      impaired on the Morris Water Maze, with some residual deficits in spatial memory
      observed more than 6 weeks after the end of sucrose exposure. Further, results
      from outcome devaluation testing indicated that in the older cohort of rats,
      those fed sucrose showed reduced sensitivity to devaluation of the outcome,
      suggestive of differences in instrumental learning following sucrose exposure.
      Data provide strong evidence that sucrose consumption can induce deficits in
      spatial cognition and reward-oriented behavior at levels that resemble patterns
      of sugar drink consumption in young people, and which can remain long after
      exposure.

PMID- 23954408
TI  - Delay discounting task in pigs reveals response strategies related to dopamine
      metabolite.
AB  - We developed a novel delay discounting task to investigate outcome impulsivity in
      pigs. As impulsivity can affect aggression, and might also relate to proactive
      and reactive coping styles, eight proactive (HR) and eight reactive (LR) pigs
      identified in a manual restraint test ("Backtest", after Bolhuis et al., 2003)
      were weaned and mixed in four pens of four unfamiliar pigs, so that each pen had
      two HR and two LR pigs, and aggression was scored in the 9h after mixing. In the
      delay discounting task, each pig chose between two levers, one always delivering
      a small immediate reward, the other a large delayed reward with daily increasing
      delays, impulsive individuals being the ones discounting the value of the large
      reward quicker. Two novel strategies emerged: some pigs gradually switched their
      preference towards the small reward ('Switchers') as predicted, but others
      persistently preferred the large reward until they stopped making choices
      ('Omitters'). Outcome impulsivity itself was unrelated to these strategies, to
      urinary serotonin metabolite (5-HIAA) or dopamine metabolite (HVA) levels,
      aggression at weaning, or coping style. However, HVA was relatively higher in
      Omitters than Switchers, and positively correlated with behavioural measures of
      indecisiveness and frustration during choosing. The delay discounting task thus
      revealed two response strategies that seemed to be related to the activity of the
      dopamine system and might indicate a difference in execution, rather than
      outcome, impulsivity. 

PMID- 23954409
TI  - Oral processing effort, appetite and acute energy intake in lean and obese
      adults.
AB  - Chewing reportedly contributes to satiation and satiety signals. Attempts to
      document and quantify this have led to small and inconsistent effects. The
      present trial manipulated oral processing effort though required chewing of gums
      of different hardness and measured appetitive sensations, energy intake, gastric
      emptying, GI transit time, and concentrations of glucose, insulin, GLP-1, ghrelin
      and pancreatic polypeptide. Sixty adults classified by sex and BMI (15 each of
      lean females, obese females, lean males and obese males) were tested in a
      randomized, controlled, cross-over trial with three arms. They chewed nothing,
      soft gum or hard gum for 15 min while sipping grape juice (10% of individual
      energy needs) containing acetaminophen and lactulose on one day each separated by
      7 days. Electromyographic recordings and self-reports were obtained during and
      after chewing to quantify oral processing effort. Blood was sampled through an
      indwelling catheter and appetite ratings were obtained at baseline and at 0, 15,
      30, 45, 60, 90, 120, 180 and 240 min after chewing initiation. Breath samples
      were collected at 10 min intervals for the first 2h and at 30 min intervals for
      the next 2h. No effects of chewing were observed for appetitive sensations or gut
      peptide concentrations. Energy intake tended to decline in lean and increase in
      obese participants so that daily energy intake differed significantly between the
      two groups when chewing either gum, while no difference was observed on the non
      chewing day. Serum glucose and insulin were significantly lower at selected time
      points 90-240 min after chewing compared to baseline and the non-chewing day.
      These data indicate chewing effort does not affect appetitive sensations or gut
      peptide secretion, but may exert a small differential effect on acute energy
      intake in lean and obese individuals and lead to greater post-prandial declines
      of serum glucose and insulin. The efficacy of gum chewing as a substitute for
      eating for weight management remains uncertain.

PMID- 23954410
TI  - Chronic stress exposure may affect the brain's response to high calorie food cues
      and predispose to obesogenic eating habits.
AB  - Exaggerated reactivity to food cues involving calorically-dense foods may
      significantly contribute to food consumption beyond caloric need. Chronic stress,
      which can induce palatable "comfort" food consumption, may trigger or reinforce
      neural pathways leading to stronger reactions to highly rewarding foods. We
      implemented functional magnetic resonance imaging (fMRI) to assess whether
      chronic stress influences activation in reward, motivation and executive brain
      regions in response to pictures of high calorie and low calorie foods in thirty
      women. On separate lab visits, we also assessed food intake from a snack food
      buffet and circulating cortisol. In women reporting higher chronic stress (HCS),
      pictures of high calorie foods elicited exaggerated activity in regions of the
      brain involving reward, motivation, and habitual decision-making. In response to
      pictures of high calorie food, higher chronic stress was also associated with
      significant deactivation in frontal regions (BA10; BA46) linked to strategic
      planning and emotional control. In functional connectivity analysis, HCS
      strengthened connectivity between amygdala and the putamen, while LCS enhanced
      connectivity between amygdala and the anterior cingulate and anterior prefrontal
      cortex (BA10). A hypocortisolemic signature and more consumption of high calorie
      foods from the snack buffet were observed in the HCS group. These results suggest
      that persistent stress exposure may alter the brain's response to food in ways
      that predispose individuals to poor eating habits which, if sustained, may
      increase risk for obesity. 

PMID- 23954411
TI  - Cutis laxa: intersection of elastic fiber biogenesis, TGFbeta signaling, the
      secretory pathway and metabolism.
AB  - Cutis laxa (CL), a disease characterized by redundant and inelastic skin,
      displays extensive locus heterogeneity. Together with geroderma osteodysplasticum
      and arterial tortuosity syndrome, which show phenotypic overlap with CL, eleven
      CL-related genes have been identified to date, which encode proteins within 3
      groups. Elastin, fibulin-4, fibulin-5 and latent transforming growth factor-beta
      binding protein 4 are secreted proteins which form elastic fibers and are
      involved in the sequestration and subsequent activation of transforming growth
      factor-beta (TGFbeta). Proteins within the second group, localized to the
      secretory pathway, perform transport and membrane trafficking functions necessary
      for the modification and secretion of elastic fiber components. Key proteins
      include a subunit of the vacuolar-type proton pump, which ensures the efficient
      secretion of tropoelastin, the precursor or elastin. A copper transporter is
      required for the activity of lysyl oxidases, which crosslink collagen and
      elastin. A Rab6-interacting goglin recruits kinesin motors to Golgi-vesicles
      facilitating the transport from the Golgi to the plasma membrane. The Rab and Ras
      interactor 2 regulates the activity of Rab5, a small guanosine triphosphatase
      essential for the endocytosis of various cell surface receptors, including
      integrins. Proteins of the third group related to CL perform metabolic functions
      within the mitochondria, inhibiting the accumulation of reactive oxygen species.
      Two of these proteins catalyze subsequent steps in the conversion of glutamate to
      proline. The third transports dehydroascorbate into mitochondria. Recent studies
      on CL-related proteins highlight the intricate connections among membrane
      trafficking, metabolism, extracellular matrix assembly, and TGFbeta signaling. 

PMID- 23954412
TI  - Collagen V localizes to pericellular sites during tendon collagen
      fibrillogenesis.
AB  - During tendon development collagen fibrillogenesis occurs in extracellular micro
      domains defined by the tenocytes. This permits cellular regulation of the
      extracellular steps involved in the tissue-specific matrix assembly required for
      function. The hypothesis tested here is that collagen V associates with the
      tenocyte surface where it functions in regulation of collagen assembly and cell
      directed fibril deposition. The in vitro and in vivo data demonstrate that
      collagen V is a quantitatively minor component of the tendon. It is
      preferentially localized on the tenocyte surface as distinct foci in tendons and
      in cell culture. In vitro data indicate that this interaction with the tenocyte
      is not HSPG GAG-dependent. Collagen V is present as the mature, processed form,
      is absent from the media, and is a significant part of the detergent-insoluble
      cell layer, presumably as part of a membrane-associated complex. In contrast,
      procollagen I is not efficiently processed and is found predominantly in the
      culture media. Our data suggest that the regulatory role of collagen V requires
      collagen V to occupy a different cellular niche from the structural collagen I.
      In monolayer cultures, the conversion to the tissue form of collagen V and its
      deposition with the cell layer suggest efficient engagement of procollagen V with
      pericellular receptors and processing enzymes. The secretion of collagen I into
      the media and inefficient processing of procollagen I suggest reduced
      accessibility to these pericellular molecules due to disengagement from the cell
      surface. This all points to differential spatial localization of collagen V as a
      mechanism to optimize its regulatory roles during the cell-surface directed steps
      in tendon collagen fibril assembly. 

PMID- 23954413
TI  - A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation
      by actin-processing factors.
AB  - Key cellular decisions, such as proliferation or growth arrest, typically occur
      at spatially defined locations within tissues. Loss of this spatial control is a
      hallmark of many diseases, including cancer. Yet, how these patterns are
      established is incompletely understood. Here, we report that physical and
      architectural features of a multicellular sheet inform cells about their
      proliferative capacity through mechanical regulation of YAP and TAZ, known
      mediators of Hippo signaling and organ growth. YAP/TAZ activity is confined to
      cells exposed to mechanical stresses, such as stretching, location at
      edges/curvatures contouring an epithelial sheet, or stiffness of the surrounding
      extracellular matrix. We identify the F-actin-capping/severing proteins Cofilin,
      CapZ, and Gelsolin as essential gatekeepers that limit YAP/TAZ activity in cells
      experiencing low mechanical stresses, including contact inhibition of
      proliferation. We propose that mechanical forces are overarching regulators of
      YAP/TAZ in multicellular contexts, setting responsiveness to Hippo, WNT, and GPCR
      signaling. 

PMID- 23954415
TI  - Strengthening blood programs in developing countries.
AB  - The lack of an adequate and safe blood supply is a major limitation to health
      care in the developing world. It is estimated that about 80% of the worlds'
      population has access to only 20% of the world's blood supply. When experts from
      the developed world attempt to provide assistance to blood programs in the
      developing world, this must be done with respect for the situation and the people
      who often work under difficult conditions. Important factors in the potential to
      strengthen blood availability and safety are government support, a national blood
      policy, the nature and leadership of the blood organization, transfusion medicine
      expertise, and hospital relations. A key first step is to carry out a needs
      assessment of the policies, governmental support, organizations, public attitudes
      about blood donation, and personnel and operations involved in providing the
      current blood supply. The important facets of the assessment are: the tool
      itself, the manner in which the assessment is conducted, and the presentation of
      the results. The assessment should provide recommendations for infrastructure,
      operations, standard procedures, testing strategies, training programs, types of
      donors and donor recruitment, budgeting, quality systems, and hospital relations.
      A sound assessment provides the groundwork and strategy for moving forward.
      Technical assistance from developed world experts to colleagues in the developing
      world can be extremely valuable in improving blood availability, safety, and the
      quality of blood services in the developing world. 

PMID- 23954416
TI  - Sickle cell anaemia: current therapies.
AB  - Tremendous progress has been made in the treatment of patients with sickle cell
      anaemia. This paper emphasises the benefit of early therapy with hydroxyurea, the
      indication for blood transfusions including iron chelation and the role of
      hematopoietic stem cell transplantation. In order to offer transplantation to a
      larger number of patients including adolescents and young adults, it is important
      to find less toxic, but still effective conditioning therapy and to evaluate the
      feasability of using alternative donors. 

PMID- 23954414
TI  - Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and
      metabolism.
AB  - The molecular mechanism of autophagy and its relationship to other lysosomal
      degradation pathways remain incompletely understood. Here, we identified a
      previously uncharacterized mammalian-specific protein, Beclin 2, which, like
      Beclin 1, functions in autophagy and interacts with class III PI3K complex
      components and Bcl-2. However, Beclin 2, but not Beclin 1, functions in an
      additional lysosomal degradation pathway. Beclin 2 is required for ligand-induced
      endolysosomal degradation of several G protein-coupled receptors (GPCRs) through
      its interaction with GASP1. Beclin 2 homozygous knockout mice have decreased
      embryonic viability, and heterozygous knockout mice have defective autophagy,
      increased levels of brain cannabinoid 1 receptor, elevated food intake, and
      obesity and insulin resistance. Our findings identify Beclin 2 as a converging
      regulator of autophagy and GPCR turnover and highlight the functional and
      mechanistic diversity of Beclin family members in autophagy, endolysosomal
      trafficking, and metabolism. 

PMID- 23954417
TI  - Novel ctxB variants of Vibrio cholerae O1 isolates, China.
AB  - We screened 650 isolates from historical collection of Vibrio cholerae O1 during
      the 7th cholera pandemic in China, by amplifying and sequencing the cholera toxin
      subunit gene ctxB. Ten isolates were identified as harboring three novel ctxB
      genotypes based on amino acid residue substitutions. Within them one isolate from
      a patient in 1964 was similar to the El Tor genotype, except for an 11 amino acid
      repeat sequence (LAGKREMAIIT) that was inserted after position 62. Six
      environmental isolates from different regions and years were identified as the
      Australia El Tor genotype, except at positions 36(T->A), 39(H->Y), and 55(K->N),
      while three environmental isolates were similar to genotype 5, except at position
      24(Q->H). Sequencing of rstR, the marker gene for the CTXPhi allele typing,
      revealed that two isolates carried the rstR gene of the El Tor type, five carried
      the classical type rstR, while other isolates carried the rstR232 type. All 10
      isolates contained the repeat in the toxin gene rtxC, an El Tor biotype-specific
      marker, and the El Tor toxin-coregulated pili subunit A gene tcpA, showing the El
      Tor traits of these isolates. Additionally, by phenotypic biotyping
      (susceptibility to polymyxin B, positive for chicken erythrocyte agglutination,
      and Voges-Proskauer test), all isolates except two were typical of the prototype
      El Tor isolate, while these two isolates had mixed classical phenotypes (hybrid
      biotype). Furthermore, pulsed-field gel electrophoresis analysis suggested that
      the new ctxB altered isolates possessed potential transmissibility and thatthey
      propagated in the local region(s). Taken together, these novel ctxB variants of
      V. cholerae O1 experienced complex hybrid and genetic exchange but belong to the
      El Tor lineage, and the pathogenic and epidemic potential of these lineages
      should be monitored. 

PMID- 23954418
TI  - A protocol to improve genotyping of problematic microsatellite loci of
      Trypanosoma brucei gambiense from body fluids.
AB  - Microsatellite genotyping of Trypanosoma brucei gambiense, the causative agent of
      human African trypanosomiasis or sleeping sickness, and population genetics
      tools, are useful for inferring population parameters such as population size and
      dispersal. Amplifying parasite DNA directly from body fluids (i.e., blood, lymph
      or cerebrospinal fluid) allows avoiding costly and tedious isolation phases. It
      is however associated to increased frequencies of amplification failures (allelic
      dropouts and/or null alleles) at some loci. In this paper, we present a study
      focused on three T. brucei gambiense microsatellite loci suspected to present
      amplification problems when amplified from body fluids sampled in Guinean
      sleeping sickness foci. We checked for the real nature of blank and apparent
      homozygous genotypes of parasite DNA directly amplified from body fluids and
      tested the effect of three different DNA quantities of trypanosomes. Our results
      show that some initially blank and homozygous genotypes happen to be actual
      heterozygous genotypes. In Guinea, lymph from the cervical nymph nodes, known to
      contain the highest concentrations of parasites, appeared to provide the best
      amplification results. Simply repeating the PCR may be enough to retrieve the
      correct genotype, but we also show that increasing initial DNA content provides
      better results while undertaking first amplification. We finally propose an
      optimal protocol for amplifying trypanosome's DNA directly from body fluids that
      should be adapted to local characteristics and/or constraints. 

PMID- 23954419
TI  - Of parasites and men.
AB  - The living world has evolved and is evolving through interspecific relationships
      between organisms. The diversity of these interactions is enormous going from
      mutualism to parasitism. Humans live with a multitude of microorganisms,
      essential for their biology. However, interactions are not always advantageous.
      Indeed, many organisms might become pathogens, such as the Plasmodium species,
      the causative agents of malaria. Like many other microorganisms, they are
      "Machiavellian" in their capacity to elaborate a range of reproduction
      strategies, giving them a huge advantage in terms of adaptation. Here, we discuss
      the role played by parasites in the ecology and evolution of living organisms and
      particularly of humans. In the study of infectious diseases, humans are
      legitimately the focal point, although they represent only one ecosystem among
      many others and not taking this into account certainly biases our global view of
      the system. Indeed, we know only a minimal fraction of the microorganisms we live
      with. However, parasites have shaped and are still shaping the human genome.
      Several genetic signatures are the proofs of the selection pressures by parasites
      that humankind has endured during its evolution. But, ultimately, what are the
      solutionsfor living with pathogens? Should we eradicate them or should we learn
      how to control and manage them? 

PMID- 23954420
TI  - Viral proteome size and CD8+ T cell epitope density are correlated: the effect of
      complexity on selection.
AB  - The relation between the complexity of organisms and proteins and their evolution
      rates has been discussed in the context of multiple generic models. The main
      robust claim from most such models is the negative relation between complexity
      and the accumulation rate of mutations. Viruses accumulate escape mutations in
      their epitopes to avoid detection and destruction of their host cell by CD8+ T
      cells. The extreme regime of immune escape, namely, strong selection and high
      mutation rate, provide an opportunity to extend and validate the existing models
      of relation between complexity and evolution rate as proposed by Fisher and
      Kimura. Using epitope prediction algorithms to compute the epitopes presented on
      the most frequent human HLA alleles in over 100 fully sequenced human viruses,
      and over 900 non-human viruses, we here study the correlation between
      viruses/proteins complexity (as measured by the number of proteins in the virus
      and the length of each protein, respectively) and the rate of accumulation of
      escape mutation. The latter is evaluated by measuring the normalized epitope
      density of viral proteins. If the virus/protein complexity prevents the
      accumulation of escape mutations, the epitope density is expected to be
      positively correlated with both the number of proteins in the virus and the
      length of proteins. We show that such correlations are indeed observed for most
      human viruses. For non-human viruses the correlations were much less significant,
      indicating that the correlation is indeed induced by human HLA molecules. 

PMID- 23954421
TI  - An in silico approach for understanding the molecular evolution of clinically
      important metallo-beta-lactamases.
AB  - Resistance to carbapenem, considered to be the drug of last resort for treating
      serious enterobacterial infections, is a growing problem. Metallo-beta-lactamase
      (MBL) mediated carbapenem resistance is considered to be clinically most
      important, since no traditional inhibitors work against them. Hence, we have
      investigated the changes in drug profile, affinity and binding stability of
      meropenem with clinically important MBLs viz., IMP, VIM and NDM during the course
      of molecular evolution. Phylogenetic trees were constructed and amino acids
      positions, presumed to be exposed to positive selection pressure were analyzed.
      Based on sequence diversity and selection pressure, IMP-1, IMP-8, IMP-9, IMP-21,
      IMP-27, IMP-20 and IMP-26 among IMP genes; VIM-1, VIM-2, VIM-13, VIM-29, VIM-18
      and VIM-7 among VIM genes and NDM-1 had been selected for in silico analysis.
      Mode of interaction of selected MBL variants with meropenem were analyzed by
      Autodock4.0 and LIGPLOT analysis. In all the trajectories, we had found an
      increase in mouth opening/solvent accessible volume/area of the catalytic pocket
      and decrease in Gibbs' free energy (DeltaG degrees ) for binding with meropenem
      and Michealis-Menten constant (Km) - indicating an increase in choice of drugs,
      binding stability and meropenem affinity from primitive to advanced MBL variants,
      with exceptions of IMP-20, IMP-26, VIM-13 and VIM-18 which might be due to sign
      epistasis. Intergenic comparison revealed NDM-1 might have greater drug profile
      and catalytic efficiency than IMP-1 and VIM-2 due to largest pocket opening and
      least distance between the Zn-I ion and beta-lactam oxygen of meropenem. 

PMID- 23954422
TI  - Oxidation-proof microemulsions: Microstructure and reactivity in the presence of
      dioxiranes.
AB  - Dioxiranes are used as reagents in a myriad of synthetically useful oxidations
      performed in aqueous medium. To extend such an approach also to substrates that
      are highly hydrophobic, we propose here the use of microemulsions based on the
      surfactant hexadecyltrimethylammonium hydrogen sulphate (CTAHS) because of its
      high stability against peroxide species. In this paper, we examine the dioxirane
      (isolated or generated in situ) reactivity in different CTAHS microemulsions.
      Yield and selectivity of the oxidation of beta-methylstyrene by dimethyldioxirane
      (DDO) generate "in situ" and of laurolactam by isolated
      methyl(trifluorometyl)dioxirane (TFDO) were studied. For each microemulsion, the
      aggregate size and the localization of the components were determined by a
      combination of NMR and light scattering techniques. The hydrodynamic radius of
      the micelles is close to the length of the surfactant and this suggests they are
      spherical in shape. When acetone (the precursor of DDO) is present in the
      formulation, it partitions itself between the aqueous bulk and the micellar
      palisade so that the dioxirane eventually formed is readily available to oxidize
      substrates secluded in the micelle. Apolar substrates, confined within the
      micelles, are protected from uncontrolled oxidations, leading to an astonishing
      high selectivity of oxidation of laurolactam to 12-nitro-lauric acid by TFDO.
      This opens the way to an easy procedure (performed in water under mild
      conditions) to synthetize omega-nitroacids. 

PMID- 23954423
TI  - Why are total knees failing today? Etiology of total knee revision in 2010 and
      2011.
AB  - Revision knee data from six joint arthroplasty centers were compiled for 2010 and
      2011 to determine mechanism of failure and time to failure. Aseptic loosening was
      the predominant mechanism of failure (31.2%), followed by instability (18.7%),
      infection (16.2%), polyethylene wear (10.0%), arthrofibrosis (6.9%), and
      malalignment (6.6%). Mean time to failure was 5.9 years (range 10 days to 31
      years). 35.3% of all revisions occurred less than 2 years after the index
      arthroplasty, 60.2% in the first 5 years. In contrast to previous reports,
      polyethylene wear is not a leading failure mechanism and rarely presents before
      15 years. Implant performance is not a predominant factor of knee failure. Early
      failure mechanisms are primarily surgeon-dependent.

PMID- 23954424
TI  - Proteomic and metabolomic analysis of earthworm Eisenia fetida exposed to
      different concentrations of 2,2',4,4'-tetrabromodiphenyl ether.
AB  - As a class of brominated flame-retardants (BFRs), polybrominated diphenyl ethers
      (PBDEs) are widely used in industrial products. PBDEs have been detected in local
      terrestrial biota from the Laizhou Bay in China. They can induce various
      toxicities, such as hepatotoxicity, neurotoxicity, cytotoxicity, genotoxicity and
      endocrine disrupting effects in animals. In this work, we characterized the dose
      responsive effects of 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) in earthworm
      Eisenia fetida using an integrated proteomic and metabolomic approach. Metabolic
      responses indicated that BDE 47 mainly caused disturbance in osmotic regulation
      and energy metabolism marked by differentially altered betaine, amino acids, ATP,
      glucose, maltose and succinate in E. fetida. Proteomic responses revealed that
      BDE 47 induced cell apoptosis (or injury), oxidative stress, disturbance in
      protein biosynthesis and energy metabolism in E. fetida in terms of differential
      proteomic biomarkers. Especially, the increased ATP was confirmed by up-regulated
      nucleoside diphosphate kinase A and ATP synthase in 1 and 100MUg/L of BDE 47
      treated groups, respectively. In addition, several metabolic biomarkers including
      betaine, glycine and 2-hexyl-5-ethyl-3-furansulfonate were relatively stable in
      all BDE 47-exposed groups. This work demonstrated that proteomics and
      metabolomics could partially validate one another and their combination could
      better understand toxicological effects of environmental pollutants. BIOLOGICAL
      SIGNIFICANCE: As a class of brominated flame-retardants (BFRs), polybrominated
      diphenyl ethers (PBDEs) are widely used in industrial products and have been
      detected in local terrestrial biota from the Laizhou Bay in China. Therefore a
      study on PBDE-induced toxicological effects is necessary. The earthworm E.
      fetida, a terrestrial sentinel animal, is the most frequently used bioindicator
      for terrestrial environmental contaminants. To our knowledge, however, very few
      studies have focused on the dose-dependent responses induced by PBDEs, in
      terrestrial sentinel animal at protein and metabolite levels. In the present
      study, an integrated metabolomic and proteomic approach was used to elucidate the
      dose-dependent toxicological effects of BDE 47 in E. fetida.

PMID- 23954425
TI  - Female Bechstein's bats adjust their group decisions about communal roosts to the
      level of conflict of interests.
AB  - Most social animals depend on group decisions for coordination. Recent models
      suggest that the level of interindividual conflict strongly influences whether
      groups reach a consensus during decision making. However, few experimental
      studies have explored how wild animals make group decisions in situations with
      conflicting interests. Such experimental data are particularly lacking for animal
      societies with regular fission and fusion of subgroups. In this long-term study,
      we varied the level of conflict of interest among members of three wild
      Bechstein's bat (Myotis bechsteinii) colonies with high fission-fusion dynamics
      experimentally to explore whether the bats adapt their group decisions about
      communal roosts accordingly. In situations with low levels of conflict of
      interest, a minority of bats experiencing a roost as suitable was sufficient for
      a group consensus to use it communally. In contrast, if their interests diverged
      strongly, the bats no longer sought a compromise, but based their roosting
      decisions on individual preferences instead. Our results demonstrate that the
      rules applied to make group decisions can vary with the level of conflict among
      the individual interests of group members. Our findings are in agreement with
      predictions of the models and provide evidence for highly flexible group
      decisions within species.

PMID- 23954426
TI  - Nonuniform distribution and spectral tuning of photosensitive retinal ganglion
      cells of the mouse retina.
AB  - Melanopsin-expressing photosensitive retinal ganglion cells (pRGCs) represent a
      third class of retinal photoreceptor. These cells are intrinsically
      photosensitive, but also receive inputs from rod and cone photoreceptors, acting
      as the primary sensory conduit mediating non-image-forming responses to light.
      Multiple subtypes of pRGC have been described in the mouse retina with
      characteristic morphologies and functional properties, and which perform distinct
      physiological roles. Here, we examine the levels of melanopsin expression and
      distribution of pRGC subtypes across the mouse retina, identifying a previously
      unreported anatomical and functional specialization of the melanopsin system. Our
      results show a dorsal-ventral gradient in the expression of melanopsin and the
      distribution of pRGCs, which, combined with dorsal-ventral gradients in
      ultraviolet-sensitive and medium-wavelength-sensitive cone opsin expression,
      produce dramatic variations in the ratio of cone opsins and pRGCs across the
      retina. Using c-fos expression as a marker of light activation in vivo, we show
      that the responses of pRGCs are spectrally tuned by gradients in cone opsin
      expression depending on their location in the retina. These data illustrate the
      importance of classical photoreceptors in providing spectral tuning of pRGC light
      responses and have important implications for the complexity of non-image-forming
      responses to light.

PMID- 23954428
TI  - Microscopic eye movements compensate for nonhomogeneous vision within the fovea.
AB  - Humans rely on the fovea, the small region of the retina where receptors are most
      densely packed, for seeing fine spatial detail. Outside the fovea, it is well
      established that a variety of visual functions progressively decline with
      eccentricity. In contrast, little is known about how vision varies within the
      central fovea, as incessant microscopic eye movements prevent isolation of
      adjacent foveal locations. Using a new method for restricting visual stimulation
      to a selected retinal region, we examined the discrimination of fine patterns at
      different eccentricities within the foveola. We show that high-acuity judgments
      are impaired when stimuli are presented just a few arcminutes away from the
      preferred retinal locus of fixation. Furthermore, we show that this dependence on
      eccentricity is normally counterbalanced by the occurrence of precisely directed
      microsaccades, which bring the preferred fixation locus onto the stimulus. Thus,
      contrary to common assumptions, vision is not uniform within the foveola, but
      targeted microscopic eye movements compensate for this lack of homogeneity. Our
      results reveal that microsaccades, like larger saccades, enable examination of
      the stimulus at a finer level of detail and suggest that a reduced precision in
      oculomotor control may be responsible for the visual acuity impairments observed
      in various disorders.

PMID- 23954427
TI  - Rapid and persistent adaptability of human oculomotor control in response to
      simulated central vision loss.
AB  - The central region of the human retina, the fovea, provides high-acuity vision.
      The oculomotor system continually brings targets of interest into the fovea via
      ballistic eye movements (saccades). Thus, the fovea serves both as the locus for
      fixations and as the oculomotor reference for saccades. This highly automated
      process of foveation is functionally critical to vision and is observed from
      infancy. How would the oculomotor system adjust to a loss of foveal vision
      (central scotoma)? Clinical observations of patients with central vision loss
      suggest a lengthy adjustment period, but the nature and dynamics of this
      adjustment remain unclear. Here, we demonstrate that the oculomotor system can
      spontaneously and rapidly adopt a peripheral locus for fixation and can
      rereference saccades to this locus in normally sighted individuals whose central
      vision is blocked by an artificial scotoma. Once developed, the fixation locus is
      retained over weeks in the absence of the simulated scotoma. Our data reveal a
      basic guiding principle of the oculomotor system that prefers control simplicity
      over optimality. We demonstrate the importance of a visible scotoma on the speed
      of the adjustment and suggest a possible rehabilitation regimen for patients with
      central vision loss.

PMID- 23954429
TI  - Chk1 inhibits E2F6 repressor function in response to replication stress to
      maintain cell-cycle transcription.
AB  - BACKGROUND: In eukaryotic cells, detection of replication stress results in the
      activation of the DNA replication checkpoint, a signaling cascade whose central
      players are the kinases ATR and Chk1. The checkpoint response prevents the
      accumulation of DNA damage and ensures cell viability by delaying progression
      into mitosis. However, the role and mechanism of the replication checkpoint
      transcriptional response in human cells, which is p53 independent, is largely
      unknown. RESULTS: We show that, in response to DNA replication stress, the
      regular E2F-dependent cell-cycle transcriptional program is maintained at high
      levels, and we establish the mechanisms governing such transcriptional
      upregulation. E2F6, a repressor of E2F-dependent G1/S transcription, replaces the
      activating E2Fs at promoters to repress transcription in cells progressing into S
      phase in unperturbed conditions. After replication stress, the checkpoint kinase
      Chk1 phosphorylates E2F6, leading to its dissociation from promoters. This
      promotes E2F-dependent transcription, which mediates cell survival by preventing
      DNA damage and cell death. CONCLUSIONS: This work reveals, for the first time,
      that the regular cell-cycle transcriptional program is part of the DNA
      replication checkpoint response in human cells and establishes the molecular
      mechanism involved. We show that maintaining high levels of G1/S cell-cycle
      transcription in response to replication stress contributes to two key functions
      of the DNA replication checkpoint response, namely, preventing genomic
      instability and cell death. Given the critical role of replication stress in
      oncogene transformation, a detailed understanding of the molecular mechanisms
      involved in the checkpoint response will contribute to a better insight into
      cancer development.

PMID- 23954430
TI  - The Dionaea muscipula ammonium channel DmAMT1 provides NH4+ uptake associated
      with Venus flytrap's prey digestion.
AB  - BACKGROUND: Ammonium transporter (AMT/MEP/Rh) superfamily members mediate
      ammonium uptake and retrieval. This pivotal transport system is conserved among
      all living organisms. For plants, nitrogen represents a macronutrient available
      in the soil as ammonium, nitrate, and organic nitrogen compounds. Plants living
      on extremely nutrient-poor soils have developed a number of adaptation
      mechanisms, including a carnivorous lifestyle. This study addresses the molecular
      nature, function, and regulation of prey-derived ammonium uptake in the Venus
      flytrap, Dionaea muscipula, one of the fastest active carnivores. RESULTS: The
      Dionaea muscipula ammonium transporter DmAMT1 was localized in gland complexes
      where its expression was upregulated upon secretion. These clusters of cells
      decorating the inner trap surface are engaged in (1) secretion of an acidic
      digestive enzyme cocktail and (2) uptake of prey-derived nutrients. Voltage clamp
      of Xenopus oocytes expressing DmAMT1 and membrane potential recordings with
      DmAMT1-expressing Dionaea glands were used to monitor and compare
      electrophysiological properties of DmAMT1 in vitro and in planta. DmAMT1
      exhibited the hallmark biophysical properties of a NH4(+)-selective channel. At
      depolarized membrane potentials (Vm = 0), the Km (3.2 +/- 0.3 mM) indicated a low
      affinity of DmAMT1 for ammonium that increased systematically with negative going
      voltages. Upon hyperpolarization to, e.g., -200 mV, a Km of 0.14 +/- 0.015 mM
      documents the voltage-dependent shift of DmAMT1 into a NH4(+) transport system of
      high affinity. CONCLUSIONS: We suggest that regulation of glandular DmAMT1 and
      membrane potential readjustments of the endocrine cells provide for effective
      adaptation to varying, prey-derived ammonium sources.

PMID- 23954431
TI  - The rodent hippocampus is essential for nonspatial object memory.
AB  - Elucidating the role of the rodent hippocampus in object recognition memory is
      critical for establishing the appropriateness of rodents as models of human
      memory and for their use in the development of memory disorder treatments. In
      mammals, spatial memory and nonspatial memory depend upon the hippocampus and
      associated medial temporal lobe (MTL) structures. Although well established in
      humans, the role of the rodent hippocampus in object memory remains highly
      debated due to conflicting findings across temporary and permanent hippocampal
      lesion studies and evidence that the perirhinal cortex may support object memory.
      In the current studies, we used intrahippocampal muscimol microinfusions to
      transiently inactivate the male C57BL/6J mouse hippocampus at distinct stages
      during the novel object recognition (NOR) task: during object memory encoding and
      consolidation, just consolidation, and/or retrieval. We also assessed the effect
      of temporary hippocampal inactivation when objects were presented in different
      contexts, thus eliminating the spatial or contextual components of the task.
      Lastly, we assessed extracellular dorsal hippocampal glutamate efflux and firing
      properties of hippocampal neurons while mice performed the NOR task. Our results
      reveal a clear and compelling role of the rodent hippocampus in nonspatial object
      memory.

PMID- 23954432
TI  - Heartbeat-driven pericardiac fluid forces contribute to epicardium morphogenesis.
AB  - BACKGROUND: Hydrodynamic forces play a central role in organ morphogenesis. The
      role of blood flow in shaping the developing heart is well established, but the
      role of fluid forces generated in the pericardial cavity surrounding the heart is
      unknown. Mesothelial cells lining the pericardium generate the proepicardium
      (PE), the precursor cell population of the epicardium, the outer layer covering
      the myocardium, which is essential for its maturation and the formation of the
      heart valves and coronary vasculature. However, there is no evidence from in vivo
      studies showing how epicardial precursor cells reach and attach to the heart.
      RESULTS: Using optical tools for real-time analysis in the zebrafish, including
      high-speed imaging and optical tweezing, we show that the heartbeat generates
      pericardiac fluid advections that drive epicardium formation. These flow forces
      trigger PE formation and epicardial progenitor cell release and motion. The
      pericardial flow also influences the site of PE cell adhesion to the myocardium.
      We additionally identify novel mesothelial sources of epicardial precursors and
      show that precursor release and adhesion occur both through pericardiac fluid
      advections and through direct contact with the myocardium. CONCLUSIONS: Two
      hydrodynamic forces couple cardiac development and function: first, blood flow
      inside the heart, and second, the pericardial fluid advections outside the heart
      identified here. This pericardiac fluid flow is essential for epicardium
      formation and represents the first example of hydrodynamic flow forces
      controlling organogenesis through an action on mesothelial cells.

PMID- 23954433
TI  - Lre1 directly inhibits the NDR/Lats kinase Cbk1 at the cell division site in a
      phosphorylation-dependent manner.
AB  - BACKGROUND: The nuclear Dbf2 related (NDR) family of protein kinases play
      important roles in cell-cycle regulation, apoptosis, cell morphogenesis, and
      development in a variety of organisms. In budding yeast, the NDR kinase complex
      composed of Cbk1 and its regulatory subunit, Mob2, have an established role in
      the control of cell separation/abscission that follows cytokinesis. Whereas the
      activators of Cbk1-Mob2 have been more extensively described, the mechanisms that
      restrict or inhibit Cbk1-Mob2 catalytic activity remain largely unknown. RESULTS:
      We identified the protein Lre1 as a direct inhibitor of Cbk1-Mob2 catalytic
      activity. We show that Lre1 accumulates at the cell division site in late
      anaphase and associates with both Mob2 and Cbk1 in vivo and in vitro. Biochemical
      and functional analysis established that the ability of Lre1 to associate with
      Cbk1-Mob2 was reduced by mitotic Cdk1 activity and promoted by Cdc14 phosphatase
      at the end of mitosis. The inhibition of Cbk1-Mob2 by Lre1 was critical to
      promote the survival of cells lacking the actomyosin driven pathway of
      cytokinesis. CONCLUSIONS: We established Lre1 as a direct inhibitor of the NDR
      kinase Cbk1-Mob2, which is regulated in a cell-cycle-dependent manner. We propose
      that similar inhibitory proteins may also provide fine tuning for the activity of
      NDR kinases in other organisms.

PMID- 23954434
TI  - Life history strategy influences parasite responses to habitat fragmentation.
AB  - Anthropogenic habitat use is a major threat to biodiversity and is known to
      increase the abundance of generalist host species such as rodents, which are
      regarded as potential disease carriers. Parasites have an intimate relationship
      with their host and the surrounding environment and it is expected that habitat
      fragmentation will affect parasite infestation levels. We investigated the effect
      of habitat fragmentation on the ecto- and endoparasitic burdens of a broad niche
      small mammal, Rhabdomys pumilio, in the Western Cape Province, South Africa. Our
      aim was to look at the effects of fragmentation on different parasite species
      with diverse life history characteristics and to determine whether general
      patterns can be found. Sampling took place within pristine lowland
      (Fynbos/Renosterveld) areas and at fragmented sites surrounded and isolated by
      agricultural activities. All arthropod ectoparasites and available
      gastrointestinal endoparasites were identified. We used conditional
      autoregressive models to investigate the effects of habitat fragmentation on
      parasite species richness and abundance of all recovered parasites. Host density
      and body size were larger in the fragments. Combined ecto- as well as combined
      endoparasite taxa showed higher parasite species richness in fragmented sites.
      Parasite abundance was generally higher in the case of R. pumilio individuals in
      fragmented habitats but it appears that parasites that are more permanently
      associated with the host's body and those that are host-specific show the
      opposite trend. Parasite life history is an important factor that needs to be
      considered when predicting the effects of habitat fragmentation on parasite and
      pathogen transmission. 

PMID- 23954435
TI  - The epidemiology and public health importance of toxocariasis: a zoonosis of
      global importance.
AB  - Toxocariasis, caused by infection with larvae of Toxocara canis, and to a lesser
      extent by Toxocara cati and other ascaridoid species, manifests in humans in a
      range of clinical syndromes. These include visceral and ocular larva migrans,
      neurotoxocariasis and covert or common toxocariasis. Toxocara canis is one of the
      most widespread public health and economically important zoonotic parasitic
      infections humans share with dogs, cats and wild canids, particularly foxes. This
      neglected disease has been shown through seroprevalence studies to be especially
      prevalent among children from socio-economically disadvantaged populations both
      in the tropics and sub-tropics and in industrialised nations. Human infection
      occurs by the accidental ingestion of embryonated eggs or larvae from a range of
      wild and domestic paratenic hosts. Most infections remain asymptomatic.
      Clinically overt infections may go undiagnosed, as diagnostic tests are expensive
      and can require serological, molecular and/or imaging tests, which may not be
      affordable or available. Treatment in humans varies according to symptoms and
      location of the larvae. Anthelmintics, including albendazole, thiabendazole and
      mebendazole may be given together with anti-inflammatory corticosteroids. The
      development of molecular tools should lead to new and improved strategies for the
      treatment, diagnosis and control of toxocariasis and the role of other ascaridoid
      species in the epidemiology of Toxocara spp. Molecular technologies may also help
      to reveal the public health importance of T. canis, providing new evidence to
      support the implementation of national control initiatives which have yet to be
      developed for Toxocara spp. A number of countries have implemented reproductive
      control programs in owned and stray dogs to reduce the number of young dogs in
      the population. These programs would positively impact upon T. canis transmission
      since the parasite is most fecund and prevalent in puppies. Other control
      measures for T. canis include the regular and frequent anthelmintic treatment of
      dogs and cats, starting at an early age, education and enforcement of laws for
      the disposal of canine faeces, dog legislation and personal hygiene. The
      existence of wild definitive and paratenic hosts complicates the control of T.
      canis. Increasing human and dog populations, population movements and climate
      change will all serve to increase the importance of this zoonosis. This review
      examines the transmission, diagnosis and clinical syndromes of toxocariasis, its
      public health importance, epidemiology, control and current research needs. 

PMID- 23954436
TI  - Metabonomic study on the biochemical response of spontaneously hypertensive rats
      to chronic taurine supplementation using (1)H NMR spectroscopic urinalysis.
AB  - There is a wealth of experimental information and some clinical evidence
      available in the literature suggesting that taurine exerts preventive effects on
      cardiovascular diseases. In particular, taurine has been shown to reduce blood
      pressure in not only hypertensive patients but also in a number of hypertensive
      rodent models such as spontaneously hypertensive rats (SHR). However, the
      molecular basis of the efficacy and toxicity of the compound has not been fully
      characterized. We have investigated the effects of taurine supplementation to
      urinary low-molecular-weight endogenous metabolites in SHR using a (1)H NMR-based
      urinary metabonomic approach. The SHR were chronically treated with 3% taurine in
      drinking water from four to 14 weeks of age, and 24-h urine samples were analyzed
      using (1)H NMR spectroscopy. Metabolic information was extracted from the NMR
      data by principal components analysis as well as visual inspection. Consequently,
      the metabolite profile started to change with considerable interindividual
      variation from six weeks of age. The extent of change became increasingly
      remarkable with the duration of treatment, with the concurrent observation of the
      hypotensive effect. The metabolic changes included a decreased urinary output of
      tricarboxylic acid cycle intermediates (citrate, alpha-ketoglutarate, and
      succinate) and an increased output of phenylacetylglycine and p-cresol sulfate.
      The results suggest that chronic taurine supplementation to the SHR resulted in
      an acceleration of metabolic acidosis with perturbation in the tricarboxylic acid
      cycle and the modulation of the intestinal microbial metabolism. 

PMID- 23954437
TI  - Drug interference in immunogenicity assays depends on valency.
AB  - Direct comparison of immunogenicity data is hampered by differential drug
      interference in different assay formats. In this paper we identify a drug-related
      factor that influences the extent of drug interference. We systematically
      investigated the influence of drug valency of different antibody-derived
      biologicals on the drug interference, using mono- and bivalent formats of
      adalimumab as a model system. Our results indicate that compared to regular
      bivalent antibodies, antibody-derived drugs that are monovalent result in less
      drug interference. Two real-life examples were examined: natalizumab, an IgG4
      antibody that becomes effectively monovalent in vivo due to Fab arm exchange, and
      certolizumab pegol, a pegylated Fab fragment. For both drugs it was demonstrated
      that drug interference is less pronounced in an antigen-binding test compared to
      similar assays for other therapeutic antibodies. When comparing immunogenicity
      data obtained for different biologicals this phenomenon should be taken into
      account. 

PMID- 23954438
TI  - Analysis of urinary human growth hormone (hGH) using hydrogel nanoparticles and
      isoform differential immunoassays after short recombinant hGH treatment:
      preliminary results.
AB  - Successful application clinical-grade human growth hormone (hGH) immunoassays to
      the discovery of illegal doping cases has been rare. Indeed, the preferred
      biological matrix in doping control is urine, where the estimated baseline
      concentration of hGH falls well below the linear range and sensitivity threshold
      of all commercially available immunoassays, including hGH isoform differential
      immunoassays which can discriminate pituitary endogenous hGH from recombinant
      hGH. We employed hydrogel nanoparticles as a pre-processing step that concentrate
      urinary hGH into the linear range of isoform differential immunoassays. We
      explored the characteristics of immunoassays in urine spiked with both phGH or
      rhGH, after pre-treatment with the nanoparticles. Subsequently, pre-treatment was
      applied to urine obtained from 3 healthy volunteers administered during three
      days with daily subcutaneous injections of 0.026 mg/kg/day rhGH, Genotonorm((r)).
      Linearity between both rhGH and phGH concentrations in urine measured by a
      chemoluminescent assay (Immulite) and in the particle eluate was evident for
      differential immunoassays (R square higher than 0.999). In case of treated
      individuals the recombinant/pituitary concentration ratios remained above the
      established World Anti-Doping Agency (WADA) criterion for hGH misuse up to 24h
      after the last administration dose, using both assays for volunteer 1 and 2 while
      in case of volunteer 3 results were inconclusive. The use of nanoparticles
      appears to open the possibility of assessing rhGH misuse in urine.

PMID- 23954439
TI  - Reduced CNS exposure of memantine in a triple transgenic mouse model of
      Alzheimer's disease assessed using a novel LC-MS technique.
AB  - A sensitive and robust LC-MS method for quantifying memantine (MEM)
      concentrations in mouse brain homogenate and perfusate was developed and
      validated. The developed LC-MS method exhibited good linearity between response
      and MEM concentrations in both perfusate and brain homogenate (r(2)=0.98-0.99)
      with mean accuracy and precision values of 105.6% and 7.7% (for perfusate) and
      99.0% and 9.5% (for brain homogenate). This assay was then applied to determine
      the impact of reported blood-brain barrier (BBB) alterations in Alzheimer's
      disease (AD) on the CNS exposure of the anti-AD drug, MEM. The brain uptake of
      MEM was measured in 12-13 and 17-19 month old wild-type (WT) and triple
      transgenic (3 * Tg) AD mice using the developed LC-MS assay and a transcardiac
      perfusion technique. The transcardiac perfusion technique was validated in our
      laboratory with marker compounds (each representing different mechanisms of
      transport across the BBB) to ascertain that the physical and functional
      properties of the BBB were maintained using this technique. While the brain
      uptake of MEM was not significantly different between WT and 3 * Tg mice at 12-13
      months, MEM brain uptake was significantly (p<0.05) decreased by 43% in 17-19
      month old 3 * Tg mice relative to WT mice. Using this novel LC-MS technique, the
      CNS exposure of a therapeutically-relevant drug, MEM, has been shown to be
      decreased in AD, implying a need to assess the impact of this disorder on the
      brain uptake of other therapeutically-relevant compounds.

PMID- 23954440
TI  - Data gaps in toxicity testing of chemicals allowed in food in the United States.
AB  - In the United States, chemical additives cannot be used in food without an
      affirmative determination that their use is safe by FDA or additive manufacturer.
      Feeding toxicology studies designed to estimate the amount of a chemical additive
      that can be eaten safely provide the most relevant information. We analyze how
      many chemical additives allowed in human food have feeding toxicology studies in
      three toxicological information sources including the U.S. Food and Drug
      Administration's (FDA) database. Less than 38% of FDA-regulated additives have a
      published feeding study. For chemicals directly added to food, 21.6% have feeding
      studies necessary to estimate a safe level of exposure and 6.7% have reproductive
      or developmental toxicity data in FDA's database. A program is needed to fill
      these significant knowledge gaps by using in vitro and in silico methods
      complemented with targeted in vivo studies to ensure public health is protected. 

PMID- 23954441
TI  - Identification of the kinesin KifC3 as a new player for positioning of
      peroxisomes and other organelles in mammalian cells.
AB  - The attachment of organelles to the cytoskeleton and directed organelle transport
      is essential for cellular morphology and function. In contrast to other cell
      organelles like the endoplasmic reticulum or the Golgi apparatus, peroxisomes are
      evenly distributed in the cytoplasm, which is achieved by binding of peroxisomes
      to microtubules and their bidirectional transport by the microtubule motor
      proteins kinesin-1 (Kif5) and cytoplasmic dynein. KifC3, belonging to the group
      of C-terminal kinesins, has been identified to interact with the human peroxin
      PEX1 in a yeast two-hybrid screen. We investigated the potential involvement of
      KifC3 in peroxisomal transport. Interaction of KifC3 and the AAA-protein (ATPase
      associated with various cellular activities) PEX1 was confirmed by in vivo
      colocalization and by coimmunoprecipitation from cell lysates. Furthermore,
      knockdown of KifC3 using RNAi resulted in an increase of cells with perinuclear
      clustered peroxisomes, indicating enhanced minus-end directed motility of
      peroxisomes. The occurrence of this peroxisomal phenotype was cell cycle phase
      independent, while microtubules were essential for phenotype formation. We
      conclude that KifC3 may play a regulatory role in minus-end directed peroxisomal
      transport for example by blocking the motor function of dynein at peroxisomes.
      Knockdown of KifC3 would then lead to increased minus-end directed peroxisomal
      transport and cause the observed peroxisomal clustering at the microtubule
      organizing center. 

PMID- 23954442
TI  - Epigenetic upregulation of Bak by ZBP-89 inhibits the growth of hepatocellular
      carcinoma.
AB  - Zinc-binding protein-89 regulates Bak to facilitate apoptosis in cancer cells.
      This study examined if zinc-binding protein-89 regulates Bak through an
      epigenetic mechanism in hepatocellular carcinoma. We first demonstrated that the
      expression of Bak was reduced but the levels of deoxyribonucleic acid
      methyltransferase 1 and histone deacetylase 3 were increased in hepatocellular
      carcinoma cancer tissues compared to the corresponding non-cancer tissues.
      Moreover, there was a negative correlation between Bak expression and
      deoxyribonucleic acid methyltransferase 1 levels in hepatocellular carcinoma.
      Administration of zinc-binding protein-89 downregulated histone deacetylase 3
      expression and suppressed the activities of histone deacetylase and
      deoxyribonucleic acid methyltransferase, which led to maintenance of histone
      acetylation status, inhibited the binding of methyl-CpG-binding protein 2 to
      genomic deoxyribonucleic acid and demethylated CpG islands in the Bak promoter in
      hepatocellular carcinoma cells. Using the xenograft mouse tumor model, we
      demonstrated that zinc-binding protein-89 or inhibitors of either epigenetic
      enzymes could stimulate Bak expression, induce apoptosis, and arrest tumor growth
      and that the maximal effort was achieved when zinc-binding protein-89 and the
      enzyme inhibitors were used in combination. Conclusively, zinc-binding protein-89
      upregulates the expression of Bak by targeting multiple components of the
      epigenetic pathway in hepatocellular carcinoma. 

PMID- 23954443
TI  - Knock-down of glutaminase 2 expression decreases glutathione, NADH, and
      sensitizes cervical cancer to ionizing radiation.
AB  - Phosphate-activated mitochondrial glutaminase (GLS2) is suggested to be linked
      with elevated glutamine metabolism. It plays an important role in catalyzing the
      hydrolysis of glutamine to glutamate. The present study was to investigate the
      potent effect of GLS2 on radioresistance of cervical carcinoma. GLS2 was examined
      in 144 cases of human cervical cancer specimens (58 radioresistant specimens, 86
      radiosensitive specimens) and 15 adjacent normal cervical specimens with
      immunohistochemistry. HeLa cells were treated with a cumulative dose of 50Gy X
      rays, over 6months, yielding the resistant sub-line HeLaR. The expressions of
      GLS2 were measured by Western blot. Radioresistance was tested by colony survival
      assay. Apoptosis was determined by flow cytometry. The levels of glutathione
      (GSH), reactive oxygen species (ROS), NAD(+)/NADH ratio and NADP(+)/NADPH ratio
      were detected by quantization assay kit. Xenografts were used to confirm the
      effect of GLS2 on radioresistance in vivo. The expressions of GLS2 were
      significantly enhanced in tumor tissues of radioresistant patients compared with
      that in radiosensitive patients. In vitro, the radioresistant cell line HeLaR
      exhibited significantly increased GLS2 levels than its parental cell line HeLa.
      GLS2 silenced radioresistant cell HeLaR shows substantially enhanced
      radiosensitivity with lower colony survival and higher apoptosis in response to
      radiation. In vivo, xenografts with GLS2 silenced HeLaR were more sensitive to
      radiation. At the molecular level, knock-down of GLS2 increased the intracellular
      ROS levels of HeLaR exposed to irradiation by decreasing the productions of
      antioxidant GSH, NADH and NADPH. GLS2 may have an important role in
      radioresistance in cervical cancer patients. 

PMID- 23954444
TI  - Prevention of Reg I-induced beta-cell apoptosis by IL-6/dexamethasone through
      activation of HGF gene regulation.
AB  - Reg (regenerating gene) product, Reg protein, is induced in pancreatic beta-cells
      and acts as autocrine/paracrine growth factor for regeneration via the cell
      surface Reg receptor. However, high concentrations of Reg I protein induced beta
      cell apoptosis. In the present study, we found that hepatocyte growth factor
      (HGF) attenuated the beta-cell apoptosis induced by the high concentrations of
      Reg I protein and that the combined stimulation of interleukin-6 (IL-6) and
      dexamethasone (Dx) induced the accumulation of HGF mRNA as well as Reg I mRNA in
      beta-cells. The accumulation of the HGF mRNA was caused by the activation of the
      HGF promoter. Deletion analysis revealed that the region of -96 to -92 of the HGF
      gene was responsible for the promoter activation by IL-6+Dx. The promoters
      contain a consensus transcription factor binding sequence for signal transducer
      and activator of transcription (STAT). Site-directed mutations of STAT-binding
      motif in the region markedly attenuated the HGF promoter activity. Chromatin
      immunoprecipitation assay showed that STAT3 is located at the active HGF promoter
      in response to IL-6+Dx stimulation. These results strongly suggest that the
      combined stimulation of IL-6 and glucocorticoids induces the activation of both
      Reg and HGF genes and that the anti-apoptotic effects of HGF against the Reg I
      induced apoptosis may help beta-cell regeneration by Reg I protein. 

PMID- 23954446
TI  - 'Food hates' over the life course: an analysis of food narratives from the UK
      Mass Observation Archive.
AB  - This article presents data from the UK Mass Observation Archive drawn from the
      1982 Winter Food Directive, which focuses on memories of childhood food 'hates'.
      Through our analysis of these data, we identify three main findings: (a) there is
      a discrepancy between individual-level and collective aggregate level food hates,
      which problematises the notion of commensality; (b) a small but powerful
      'outlier' group of respondents, which we refer to as 'visceral repulsors', show
      relatively extreme reactions to certain foods throughout their lives; and (c) the
      duration and temporalities of food hates can be used to sketch a rough model of
      change and continuity of food hates over the life course. Finally, the discussion
      focuses on the food hate trajectories through the life course, situated in a
      social context, to explore the implications the findings may have for food and
      health policy more generally. 

PMID- 23954447
TI  - Neurological drug development: a guide for a start-up biotech.

PMID- 23954448
TI  - Vagus nerve stimulation during rehabilitative training improves forelimb strength
      following ischemic stroke.
AB  - Upper limb impairment is a common debilitating consequence of ischemic stroke.
      Physical rehabilitation after stroke enhances neuroplasticity and improves limb
      function, but does not typically restore normal movement. We have recently
      developed a novel method that uses vagus nerve stimulation (VNS) paired with
      forelimb movements to drive specific, long-lasting map plasticity in rat primary
      motor cortex. Here we report that VNS paired with rehabilitative training can
      enhance recovery of forelimb force generation following infarction of primary
      motor cortex in rats. Quantitative measures of forelimb function returned to pre
      lesion levels when VNS was delivered during rehab training. Intensive rehab
      training without VNS failed to restore function back to pre-lesion levels.
      Animals that received VNS during rehab improved twice as much as rats that
      received the same rehabilitation without VNS. VNS delivered during physical
      rehabilitation represents a novel method that may provide long-lasting benefits
      towards stroke recovery.

PMID- 23954445
TI  - Simultaneous knock-down of Bcl-xL and Mcl-1 induces apoptosis through Bax
      activation in pancreatic cancer cells.
AB  - Anti-apoptotic Bcl-2 family proteins have been reported to play an important role
      in apoptotic cell death of human malignancies. The aim of this study was to
      delineate the mechanism of anti-apoptotic Bcl-2 family proteins in pancreatic
      cancer (PaCa) cell survival. We first analyzed the endogenous expression and
      subcellular localization of anti-apoptotic Bcl-2 family proteins in six PaCa cell
      lines by Western blot. To delineate the functional role of Bcl-2 family proteins,
      siRNA-mediated knock-down of protein expression was used. Apoptosis was measured
      by Cell Death ELISA and Hoechst 33258 staining. In the results, the expression of
      anti-apoptotic Bcl-2 family proteins varied between PaCa cell lines. Mcl-1 knock
      down resulted in marked cleavage of PARP and induction of apoptosis. Down
      regulation of Bcl-2 or Bcl-xL had a much weaker effect. Simultaneous knock-down
      of Bcl-xL and Mcl-1 strongly induced apoptosis, but simultaneous knock-down of
      Bcl-xL/Bcl-2 or Mcl-1/Bcl-2 had no additive effect. The apoptosis-inducing effect
      of simultaneous knock-down of Bcl-xL and Mcl-1 was associated with translocation
      of Bax from the cytosol to the mitochondrial membrane, cytochrome c release, and
      caspase activation. These results demonstrated that Bcl-xL and Mcl-1 play an
      important role in pancreatic cancer cell survival. Targeting both Bcl-xL and Mcl
      1 may be an intriguing therapeutic strategy in PaCa. 

PMID- 23954449
TI  - CHD chromatin remodelling enzymes and the DNA damage response.
AB  - The protein and DNA complex known as chromatin is a dynamic structure, adapting
      to alter the spatial arrangement of genetic information within the nucleus to
      meet the ever changing demands of life. Following decades of research, a dizzying
      array of regulatory factors is now known to control the architecture of chromatin
      at nearly every level. Amongst these, ATP-dependent chromatin remodelling enzymes
      play a key role, required for the establishment, maintenance and re-organization
      of chromatin through their ability to adjust the contact points between DNA and
      histones, the spacing between individual nucleosomes and the over-arching
      chromatin superstructure. Utilizing energy from ATP hydrolysis, these enzymes
      serve as the gatekeepers of genomic access and are essential for transcriptional
      regulation, DNA replication and cell division. In recent years, a vital role in
      DNA Double Strand Break (DSB) repair has emerged, particularly within complex
      chromatin environments such as heterochromatin, or regions undergoing energetic
      transactions such as transcription or DNA replication. Here, we will provide an
      overview of what is understood about ATP-dependent chromatin remodelling enzymes
      in the context of the DNA damage response. We will first touch upon all four
      major chromatin remodelling enzyme families and then focus chiefly on the nine
      members of the Chromodomain, Helicase, DNA-binding (CHD) family, particularly
      CHD3, CHD4, CHD5 and CHD6. These four proteins have established and emerging
      roles in DNA repair, the oxidative stress response, the maintenance of genomic
      stability and/or cancer prevention. 

PMID- 23954451
TI  - Isoniazid prevention of HIV-associated tuberculosis.

PMID- 23954450
TI  - Effect of improved tuberculosis screening and isoniazid preventive therapy on
      incidence of tuberculosis and death in patients with HIV in clinics in Rio de
      Janeiro, Brazil: a stepped wedge, cluster-randomised trial.
AB  - BACKGROUND: Preventive therapy for tuberculosis in patients with HIV is
      effective, but it has not been widely implemented in moderate or high-burden
      settings. We assessed the effect of widespread use of isoniazid preventive
      therapy on rates of tuberculosis and death in people with HIV in Brazil. METHODS:
      We did a stepped wedge, cluster-randomised trial with patients actively enrolled
      in 29 HIV clinics in Rio de Janeiro. Clinic staff were trained in tuberculosis
      screening, use of tuberculin skin tests, and use of isoniazid preventive therapy.
      Clinics were randomly allocated a date to begin the intervention period, with two
      clinics beginning the intervention every 2 months starting from Sept 1, 2005. The
      primary outcome was tuberculosis incidence alone or combined with death in the
      control versus intervention periods until Aug 31, 2009. This trial is registered
      at ClinicalTrials.gov, number NCT00107887. RESULTS: Of 17,413 patients in the
      cohort, 12,816 were eligible for the intervention. Overall, there were 475
      tuberculosis cases and 838 deaths. The intervention increased the rate of
      patients receiving skin tests from 19 per 100 person-years to 59 per 100 person
      years, and from 36 per 100 person-years to 144 per 100 person-years for those
      eligible for isoniazid preventive therapy. In the control period, 221 cases of
      tuberculosis were diagnosed (1.31 per 100 person-years) compared with 254 (1.10
      per 100 person-years) in the intervention period (unadjusted hazard ratio [HR]
      0.87; 95% CI 0.69-1.10). Rates of tuberculosis incidence or death were 3.64 and
      3.04 per 100 person-years, respectively (0.76; 95% CI 0.66-0.87). When adjusted
      for age, sex, entry CD4 count, and use of antiretroviral therapy, the HR for
      tuberculosis was 0.73 (95% CI 0.54-0.99) and for tuberculosis or death was 0.69
      (0.57-0.83). INTERPRETATION: Operational training aimed at increasing
      tuberculosis screening, provision of tuberculin skin tests, and use of isoniazid
      preventive therapy in Brazilian HIV clinics significantly reduced incident
      tuberculosis and death. Thus, scale-up of preventive therapy for HIV-infected
      patients in settings of moderate tuberculosis incidence is achievable and should
      be widely implemented in Brazil and elsewhere. FUNDING: Bill & Melinda Gates
      Foundation and the National Institutes of Health.

PMID- 23954452
TI  - Echocardiography to predict tolerance to negative fluid balance in acute
      respiratory distress syndrome/acute lung injury.
AB  - PURPOSE: In acute respiratory distress syndrome (ARDS) and acute lung injury
      (ALI), a conservative fluid management strategy improves lung function but could
      jeopardize extrapulmonary organ perfusion. The objective was to evaluate the
      diagnostic accuracy of echocardiography to predict tolerance of negative fluid
      balance (NFB) in patients with ARDS/ALI. MATERIALS AND METHODS: A prospective and
      observational study in an adult intensive care unit of a university hospital was
      conducted. All hemodynamically stable patients with ARDS/ALI were included.
      Echocardiography was performed before NFB and again after 24 hours. Tolerance of
      NFB was evaluated by the presence of hypotension, acute kidney injury, or need
      for fluid expansion. The 2 patient groups (tolerating and not tolerating NFB)
      were compared. RESULTS: Forty-five patients were included. Median age (Q1-Q3) was
      58 (52-66) years, and the ratio of partial pressure of arterial oxygen to the
      fraction of inspired oxygen was 205 (163-258) mm Hg. Negative fluid balance was
      1950 (1200-2200) mL within 24 hours in the tolerant group. Complications of NFB
      were observed in 35% cases. After univariate and multivariate logistic regression
      analyzes, 2 criteria was independently associates with poor tolerance: mitral
      inflow E wave to early diastolic mitral annulus velocities ratio (E/Ea ratio;
      odds ratio, 2.02 [1.02-4.02]; P = .04) and weight gain (odds ratio, 1.2 [1.03
      1.4]; P = .02). The area under receiver operating characteristic curves was 0.74
      for E/Ea and 0.77 for weight gain. CONCLUSIONS: The ratio of E/Ea accurately
      predicted tolerance of NFB in patients with ARDS/ALI.

PMID- 23954453
TI  - Extracorporeal membrane oxygenation for severe respiratory failure in adult
      patients: a systematic review and meta-analysis of current evidence.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) for acute respiratory
      failure is still a matter of debate. METHODS: We performed a structured search on
      Pubmed, EMBASE, Lilacs, and the Cochrane Library for randomized controlled trials
      and observational case-control studies with severity-paired patients, evaluating
      the use of ECMO on severe acute respiratory failure in adult patients. A random
      effect model using DerSimonian and Laird method for variance estimator was
      performed to evaluate the effect of ECMO use on hospital mortality. Heterogeneity
      between studies was assessed with Cochran's Q statistic and Higgin's I(2).
      RESULTS: Three studies were included on the metanalysis, comprising 353 patients
      in the main analysis, in which 179 patients were ECMO supported. One study was a
      randomized controlled trial and two were observational studies with a propensity
      score matching. The most common reason for acute respiratory failure was
      influenza H1N1 pneumonia (45%) and pneumonia (33%). ECMO was not associated with
      a reduction in hospital mortality (OR = 0.71; CI 95% = 0.34 - 1.47; P = 0.358).
      If alternative severity-pairing method presented by the two observational studies
      was included, a total of 478 cases were included, in which 228 received ECMO
      support. In the former analysis, ECMO had a benefit on hospital mortality (OR =
      0.52; CI 95% = 0.35 - 0.76; P < 0.001). CONCLUSION: Extracorporeal membrane
      oxygenation benefit on hospital mortality is unclear. Results were sensitive to
      statistical analysis, and no definitive conclusion can be drawn from the
      available data. More studies are needed before the widespread use of ECMO can be
      recommended.

PMID- 23954454
TI  - Autoantibodies to coagulation factors: from pathophysiology to diagnosis and
      therapy.
AB  - Autoantibodies may develop against coagulation factors altering their function or
      promoting their rapid clearance. In non-congenitally deficient patients, they are
      usually in association with autoimmune diseases, malignancies, pregnancy or
      advanced age. The possible development of coagulation factor autoantibodies
      should be considered when a patient presents with bleeding symptoms without any
      prior bleeding diathesis. The most common disorder associated with coagulation
      factor autoantibodies is acquired factor VIII deficiency, which is characterized
      by hemorrhages involving soft tissues, muscles and skin; hemarthroses are less
      frequent than in the inherited form. Acquired deficiencies of von Willebrand
      factor and factor XIII due to autoantibodies are emerging conditions.
      Autoantibodies to the other coagulation factors may be associated with a wide
      spectrum of clinical manifestations ranging from minimal or no bleeding to life
      threatening conditions. The diagnostic approach begins with global coagulation
      tests: prothrombin time (PT) and activated partial thromboplastin time (aPTT). In
      case of prolonged times, mixing studies (typically using normal plasma in a 1:1
      proportion) should be performed. Specific factor and inhibitor assays, assessment
      of lupus anticoagulant and eventually enzyme immunoassays for specific anti
      factor antibodies complete the evaluation. A prompt diagnosis of specific
      coagulation factor inhibitors is mandatory for starting an appropriate treatment
      aimed at overcoming the deficient factor, in case of bleeding, and, if possible,
      at the suppression of the autoantibody's production. 

PMID- 23954455
TI  - Effects of artesunate and ursolic acid on hyperlipidemia and its complications in
      rabbit.
AB  - OBJECTIVE: To find the novel hypolipidemic agents, the effects of ursolic acid
      and artesunate on hyperlipidemia and its complications were determined in rabbit
      fed with Western-type diet. METHODS AND RESULTS: New Zealand rabbits fed a
      Western-type diet developed a hyperlipidemia. Rabbits received ursolic acid
      (25mg/kg) or artesunate (25mg/kg) alone, or in combination (12.5+12.5mg/kg), to
      prevent hyperlipidemia. Ursolic acid or artesunate alone significantly decreased
      the plasma cholesterol and triglyceride in rabbits. Furthermore, they both
      attenuated liver steatosis and reduced the area of aortic root lesions. The
      combination of ursolic acid and artesunate was more potent than either agent
      alone, which indicates a strong synergistic effect. CONCLUSION: The hypolipidemic
      effect of artesunate is firstly reported. Its combination with ursolic acid might
      have the potential to further develop for the treatment of atherosclerosis.

PMID- 23954456
TI  - A study on the role of (+)-catechin in suppression of HepG2 proliferation via
      caspase dependent pathway and enhancement of its in vitro and in vivo cytotoxic
      potential through liposomal formulation.
AB  - Catechin is a known hepatoprotective and anticancer agent but has limited
      bioavailability. Its apoptotic signaling pathway in human hepatocellular
      carcinoma is vaguely explored. Thus, this study was designed to explore
      cytotoxicity by MTT assay, induction of apoptosis via DNA fragmentation, nuclear
      staining, bivariate flow cytometric analysis using annexin V- FITC and propidium
      iodide, cell cycle analysis and apoptotic markers by RT-PCR and western blotting
      in HepG2 cells. To increase the bioavailability and selectivity to cancer cells,
      various liposomes of catechin viz., conventional, charged and PEGylated forms
      were prepared by film hydration method and evaluated for cytotoxicity in vitro in
      HepG2 cells and in in vivo in EAC-induced liquid tumor model. Catechin and
      catechin liposomes inhibited the growth of HepG2 cell lines at concentrations 100
      200 MUg mL(-1) depending on the length of exposure. It induced apoptosis and
      inhibited G2/M phase in cell cycle analysis. Catechin downregulated Bcl-2,
      initiated the release of cytochrome c into the cytosol and upregulated Bax,
      caspase-3,-9 and p53 in the HepG2 cells. Catechin and its liposomal formulation,
      at a dose of 200mg/kg body weight was found to be significantly (p<0.05)
      effective in inhibiting percentage increase in body weight and enhancing the mean
      survival time. Deviated hematological parameters, antioxidant parameters
      (superoxide dismutase, catalase and lipid peroxidation) and LFT in tumor bearing
      mice were found to be significantly (p<0.05) restored towards normal after
      treatment with catechin and its liposomes.

PMID- 23954457
TI  - Benefit of combined therapy with nicorandil and colchicine in preventing
      monocrotaline-induced rat pulmonary arterial hypertension.
AB  - This study tested the hypothesis that combined therapy with nicorandil and
      colchicine is superior to either alone in attenuating monocrotaline (MCT)-induced
      rat pulmonary arterial hypertension (PAH). Adult male Sprague-Dawley rats (n=50)
      were equally randomized into group 1 (sham control), group 2 [MCT (60 mg/kg
      i.p.)], group 3 [MCT-Nicorandil (5.0 mg/kg/day)], group 4 [MCT-Colchicine (1.0
      mg/kg/day)], and group 5 (MCT-Nicorandil-Colchicine). Drugs were given on day 5.
      All animals were sacrificed on day 90 after MCT administration. Right ventricular
      systolic blood pressure (RVSBP) and RV weight were increased in group 2 compared
      to group 1, reduced in groups 3 and 4 compared to group 2, and further reduced in
      group 5, whereas arterial-oxygen saturation showed an opposite pattern (all
      p<0.001). Pulmonary damage severity (thickened alveolar septum and pulmonary
      arteriolar wall, decreased alveolar-sac numbers), number of CD3+ cells, and
      protein expressions of inflammatory (MMP-9, NF-kappaB, VCAM-1, angiotensin II
      receptor), apoptotic (Bax, caspase 3, cleaved PARP), and fibrotic (TGF-beta,
      Smad3) biomarkers showed an identical pattern compared to that of RVSBP, whereas
      pulmonary expressions of anti-apoptotic (Bcl-2) and anti-fibrotic (BMP-2,
      Smad1/5) biomarkers displayed a reverse pattern (all p<0.01). The protein
      expressions of RV damage markers (BNP, caspase 3) were increased, whereas
      expression of biomarker for RV functional preservation (Cx43) was reduced in
      group 2 compared with group 1, elevated in groups 3 and 4 compared to group 2,
      and further increased in group 5 (all p<0.01). Combined therapy with nicorandil
      and colchicine is superior to either alone in attenuating MCT-induced PAH in
      rats.

PMID- 23954458
TI  - Can CT angiography rule out aneurysmal subarachnoid haemorrhage in CT scan
      negative subarachnoid haemorrhage patients?
AB  - Current management guidelines for CT scan-negative subarachnoid haemorrhage (SAH)
      patients recommend cerebral digital subtraction angiography (DSA). We aimed to
      investigate the utility of CT angiography (CTA) as a substitute for DSA in these
      patients. We included patients who presented with SAH confirmed by
      spectrophotometric xanthochromia analysis of cerebrospinal fluid (CSF) whereby
      the CT scan was negative. Electronic records were reviewed to collect data on non
      contrast CT scan, CTA and DSA results. Patients without DSA or with other
      explanations for CSF xanthochromia were excluded. Sixty-three patients with CT
      scan-negative SAH were included. The diagnosis of SAH was confirmed by CSF
      analysis. All 63 patients underwent both DSA and CTA. Using DSA as the benchmark,
      CTA demonstrated a negative predictive value, positive predictive value,
      sensitivity and specificity of 98%, 82%, 90% and 96%, respectively, for the
      detection of intracranial aneurysms. CTA correctly identified patients in whom
      there were no underlying aneurysms responsible for SAH, with one patient with
      suspected dissection referred for further evaluation using MRI and DSA. 

PMID- 23954459
TI  - Spinal neurofibromatosis in a family with classical neurofibromatosis type 1 and
      a novel NF1 gene mutation.
AB  - Familial spinal neurofibromatosis (FSNF) is a rare form of neurofibromatosis type
      1 (NF1) characterized by multiple, histologically proven neurofibromas of the
      spinal roots leaving no intact segments and associated neurofibromas of major
      peripheral nerves. It is sometimes associated with other NF1 stigmata. Most
      patients have NF1 gene mutations. We describe a patient who fulfilled the
      diagnostic criteria for spinal neurofibromatosis and belonged to a family in
      which other affected members exhibited classical NF1 stigmata. A novel missense
      (c.7109 T>A; p.Val2370Asp) mutation in exon 39 of the NF1 gene was present in the
      affected family members. The family displayed extreme phenotypic variability in
      the spectrum of NF1. To our knowledge, this is the first patient with spinal
      neurofibromatosis in the context of classical NF1 with an NF1 gene mutation. The
      term FSNF is inaccurate as this condition simply reflects the typical autosomal
      dominant pattern of NF1 inheritance with phenotypoc variability and does not
      encompass patients with sporadic disease or those in the context of a classical
      NF1 phenotype as reported in the present family. The term could be replaced by
      "spinal neurofibromatosis".

PMID- 23954460
TI  - Pathophysiology of acute hydrocephalus after subarachnoid hemorrhage.

PMID- 23954461
TI  - Deep brain stimulation for cognitive disorders: insights into targeting nucleus
      basalis of meynert in Alzheimer dementia.

PMID- 23954462
TI  - Terson syndrome: an often overlooked complication of subarachnoid hemorrhage.

PMID- 23954463
TI  - Primary Ewing sarcoma of the iris.

PMID- 23954464
TI  - Is the assumption of normality or log-normality for continuous response data
      critical for benchmark dose estimation?
AB  - Continuous responses (e.g. body weight) are widely used in risk assessment for
      determining the benchmark dose (BMD) which is used to derive a U.S. EPA reference
      dose. One critical question that is not often addressed in dose-response
      assessments is whether to model the continuous data as normally or log-normally
      distributed. Additionally, if lognormality is assumed, and only summarized
      response data (i.e., mean+/-standard deviation) are available as is usual in the
      peer-reviewed literature, the BMD can only be approximated. In this study, using
      the "hybrid" method and relative deviation approach, we first evaluate six
      representative continuous dose-response datasets reporting individual animal
      responses to investigate the impact on BMD/BMDL estimates of (1) the distribution
      assumption and (2) the use of summarized versus individual animal data when a log
      normal distribution is assumed. We also conduct simulation studies evaluating
      model fits to various known distributions to investigate whether the distribution
      assumption has influence on BMD/BMDL estimates. Our results indicate that BMDs
      estimated using the hybrid method are more sensitive to the distribution
      assumption than counterpart BMDs estimated using the relative deviation approach.
      The choice of distribution assumption has limited impact on the BMD/BMDL
      estimates when the within dose-group variance is small, while the lognormality
      assumption is a better choice for relative deviation method when data are more
      skewed because of its appropriateness in describing the relationship between mean
      and standard deviation. Additionally, the results suggest that the use of
      summarized data versus individual response data to characterize log-normal
      distributions has minimal impact on BMD estimates. 

PMID- 23954466
TI  - A novel natural Nrf2 activator with PPARgamma-agonist (monascin) attenuates the
      toxicity of methylglyoxal and hyperglycemia.
AB  - Methylglyoxal (MG) is a toxic-glucose metabolite and a major precursor of
      advanced glycation endproducts (AGEs). MG has been reported to result in
      inflammation by activating receptor for AGEs (RAGE). We recently found that
      Monascus-fermented metabolite monascin acts as a novel natural peroxisome
      proliferator-activated receptor-gamma (PPARgamma) agonist that improves insulin
      sensitivity. We investigated the metabolic, biochemical, and molecular
      abnormalities characteristic of type 2 diabetes in MG-treated Wistar rats treated
      with oral administration of monascin or rosiglitazone. Monascin (a novel
      PPARgamma agonist) activated nuclear factor-erythroid 2-related factor 2 (Nrf2)
      and down-regulated hyperinsulinmia in oral glucose tolerance test (OGTT).
      Monascin was able to elevate glyoxalase-1 expression via activation of hepatic
      Nrf2, hence, resulting in MG metabolism to d-lactic acid and protected from AGEs
      production in MG-treated rats. Rosiglitazone did not activate Nrf2 nor glyoxalase
      expression to lower serum and hepatic AGEs levels. Monascin acts as a novel
      natural Nrf2 activator with PPARgamma-agonist activity were confirmed by Nrf2 and
      PPARgamma reporter assays in Hep G2 cells. These findings suggest that monascin
      acts as an anti-diabetic and anti-oxidative stress agent to a greater degree than
      rosiglitazone and thus may have therapeutic potential for the prevention of
      diabetes. 

PMID- 23954465
TI  - Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and
      promotes Nrf2-related neurite outgrowth.
AB  - Reactive oxygen intermediates production and apoptotic damage induced by high
      glucose are major causes of neuronal damage in diabetic neuropathy. Berberine
      (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise
      for diabetes because of its dual antioxidant and anti-apoptotic activities. We
      have previously reported that BBR attenuated H2O2 neurotoxicity via activating
      the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel
      protective mechanism of BBR on high glucose-induced apoptotic death and neurite
      damage of SH-SY5Y cells. Results indicated BBR (0.1-10 nM) significantly
      attenuated reactive oxygen species (ROS) production, nucleus condensation, and
      apoptotic death in high glucose-treated cells. However, AG1024, an inhibitor of
      insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection
      against high glucose-induced neuronal death. BBR also increased Bcl-2 expression
      and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor
      and phosphorylation of Akt and GSK-3beta, the effects of which were attenuated by
      BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2),
      the key antioxidative transcription factor, which is accompanied with up
      regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve
      growth factor (NGF) expression and promoted neurite outgrowth in high glucose
      treated cells. To further determine the role of the Nrf2 in BBR neuroprotection,
      RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA
      abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In
      conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the
      first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose
      neurotoxicity, providing another potential therapeutic use of BBR on the
      treatment of diabetic complications.

PMID- 23954467
TI  - Teroxirone inhibited growth of human non-small cell lung cancer cells by
      activating p53.
AB  - In this work, we demonstrated that the growth of human non-small-cell-lung-cancer
      cells H460 and A549 cells can be inhibited by low concentrations of an epoxide
      derivative, teroxirone, in both in vitro and in vivo models. The cytotoxicity was
      mediated by apoptotic cell death through DNA damage. The onset of ultimate
      apoptosis is dependent on the status of p53. Teroxirone caused transient
      elevation of p53 that activates downstream p21 and procaspase-3 cleavage. The
      presence of caspase-3 inhibitor reverted apoptotic phenotype. Furthermore, we
      showed the cytotoxicity of teroxirone in H1299 cells with stable ectopic
      expression of p53, but not those of mutant p53. A siRNA-mediated knockdown of p53
      expression attenuated drug sensitivity. The in vivo experiments demonstrated that
      teroxirone suppressed growth of xenograft tumors in nude mice. Being a potential
      therapeutic agent by restraining cell growth through apoptotic death at low
      concentrations, teroxirone provides a feasible perspective in reversing
      tumorigenic phenotype of human lung cancer cells. 

PMID- 23954468
TI  - Lactulose ameliorates cerebral ischemia-reperfusion injury in rats by inducing
      hydrogen by activating Nrf2 expression.
AB  - Molecular hydrogen has been proven effective in ameliorating cerebral
      ischemia/reperfusion (I/R) injury by selectively neutralizing reactive oxygen
      species. Lactulose can produce a considerable amount of hydrogen through
      fermentation by the bacteria in the gastrointestinal tract. To determine the
      neuroprotective effects of lactulose against cerebral I/R injury in rats and
      explore the probable mechanisms, we carried out this study. The stroke model was
      produced in Sprague-Dawley rats through middle cerebral artery occlusion.
      Intragastric administration of lactulose substantially increased breath hydrogen
      concentration. Behavioral and histopathological verifications matched biochemical
      findings. Behaviorally, rats in the lactulose administration group won higher
      neurological scores and showed shorter escape latency time in the Morris test.
      Morphologically, 2,3,5-triphenyltetrazolium chloride showed smaller infarction
      volume; Nissl staining manifested relatively clear and intact neurons and TUNEL
      staining showed fewer apoptotic neurons. Biochemically, lactulose decreased brain
      malondialdehyde content, caspase-3 activity, and 3-nitrotyrosine and 8-hydroxy-2
      deoxyguanosine concentration and increased superoxide dismutase activity. The
      effects of lactulose were superior to those of edaravone. Lactulose orally
      administered activated the expression of NF-E2-related factor 2 (Nrf2) in the
      brain as verified by RT-PCR and Western blot. The antibiotics suppressed the
      neuroprotective effects of lactulose by reducing hydrogen production. Our study
      for the first time demonstrates a novel therapeutic effect of lactulose on
      cerebral ischemia/reperfusion injury and the probable underlying mechanisms.
      Lactulose intragastrically administered possessed neuroprotective effects on
      cerebral I/R injury in rats, which could be attributed to hydrogen production by
      the fermentation of lactulose through intestinal bacteria and Nrf2 activation. 

PMID- 23954469
TI  - DNA oxidative damage in mammalian spermatozoa: where and why is the male nucleus
      affected?
AB  - Gamete DNA integrity is one key parameter conditioning reproductive success as
      well as the quality of life for the offspring. In particular, damage to the male
      nucleus can have profound negative effects on the outcome of fertilization.
      Because of the absence of repair activity of the quiescent mature spermatozoa it
      is easily subjected to nuclear damage, of which oxidative damage is by far the
      most prominent. In relation to the organization of the mammalian sperm nucleus we
      show here that one can correlate the nuclear regions of lower compaction with
      areas preferentially showing oxidative damage. More precisely, we show that
      oxidative DNA damage targets primarily histone-rich and nuclear matrix-attached
      domains located in the peripheral and basal regions of the mouse sperm nucleus.
      These particular sperm DNA domains were recently shown to be enriched in genes of
      paramount importance in postfertilization DNA replication events and in the onset
      of the embryonic developmental program. We propose that monitoring of sperm DNA
      oxidation using the type of assay presented here should be considered in clinical
      practice when one wants to estimate the integrity of the paternal nucleus along
      with more classical assays that essentially analyze DNA fragmentation and nucleus
      compaction. 

PMID- 23954470
TI  - Oxidative stress and inflammation in the normal airways and blood of patients
      with lung cancer and COPD.
AB  - Respiratory conditions such as chronic obstructive pulmonary disease (COPD) are
      associated with a greater risk for lung cancer (LC). Oxidative stress and
      inflammation are involved in LC pathophysiology. Studies conducted so far have
      focused solely on lung tumor parenchyma and not the airways. We explored levels
      of local and systemic oxidative stress and inflammation within normal bronchial
      epithelium and blood of patients with lung cancer (n=52), with and without COPD,
      and in control subjects (COPD and non-COPD, n=21). In normal bronchial epithelium
      specimens (bronchoscopy) and blood from patients with similar smoking history (LC
      COPD and LC) and control subjects (both COPD and non-COPD), redox balance and
      inflammatory markers were measured (ELISA and immunoblotting). All subjects were
      clinically evaluated. Absence of malignant cells within the bronchial specimens
      was always pathologically confirmed. Bronchial levels of protein carbonylation,
      MDA-protein adducts, antioxidants, TNF-alpha, interferon-gamma, TGF-beta, and
      VEGF and blood levels of superoxide anion, oxidatively damaged DNA and proteins,
      TNF-alpha, interferon-gamma, TGF-beta, VEGF, and neutrophils were significantly
      greater in all LC patients compared to control subjects. Systemic levels of
      oxidatively damaged DNA, superoxide anion, and TNF-alpha and bronchial levels of
      TGF-beta and TNF-alpha showed high sensitivity and specificity for LC among
      patients. Regardless of the presence of an underlying respiratory condition
      (COPD), protein oxidation, oxidatively damaged DNA, and inflammation were
      remarkably increased in the normal airways and blood of patients with LC.
      Furthermore, the potential predictive value for LC development of these molecular
      events warrants attention and should be explored in future larger longitudinal
      studies. 

PMID- 23954471
TI  - The protective action of ketanserin against lipopolysaccharide-induced shock in
      mice is mediated by inhibiting inducible NO synthase expression via the MEK/ERK
      pathway.
AB  - Nitric oxide (NO) plays an important role in the pathogenesis of endotoxic shock.
      This work tested the hypothesis that ketanserin could attenuate endotoxic shock
      by inhibiting the expression of inducible NO synthase (iNOS). The results
      demonstrated that ketanserin could inhibit iNOS expression in the heart, lungs,
      liver, and kidneys and nitrate production in the serum upon endotoxic shock in
      mice. In RAW264.7 cells, ketanserin significantly inhibited the expression of
      iNOS and decreased the production of NO, TNFalpha, IL-6, and reactive oxygen
      species upon lipopolysaccharide (LPS) challenge. Ketanserin also increased the
      level of ATP and mitochondrial membrane potential in RAW264.7 cells upon LPS
      exposure. LPS-induced iNOS expression was inhibited by the 5-HT2A receptor
      antagonist ritanserin and not the alpha1 receptor antagonist prazosin. Knockdown
      of 5-HT2A receptor by siRNA abolished the inhibitory effect of ketanserin on the
      expression of iNOS. These results indicated that the inhibitory effect of
      ketanserin on the expression of iNOS is mediated by blocking the 5-HT2A receptor.
      Furthermore, ketanserin significantly inhibited the activation of ERK1/2 and NF
      kappaB signal. Pretreatment with PD184352, a specific inhibitor of ERK1/2,
      blocked the inhibitory effect of ketanserin on the expression of iNOS and NO
      production, indicating a critical role for the MEK/ERK1/2 signaling pathway.
      Collectively, our findings indicate that inhibition of the expression of iNOS via
      the MEK/ERK pathway mediates the protective effects of ketanserin against LPS
      induced shock in mice. 

PMID- 23954473
TI  - Probability state modeling of memory CD8+ T-cell differentiation.
AB  - Flow cytometric analysis enables the simultaneous single-cell interrogation of
      multiple biomarkers for phenotypic and functional identification of heterogeneous
      populations. Analysis of polychromatic data has become increasingly complex with
      more measured parameters. Furthermore, manual gating of multiple populations
      using standard analysis techniques can lead to errors in data interpretation and
      difficulties in the standardization of analyses. To characterize high-dimensional
      cytometric data, we demonstrate the use of probability state modeling (PSM) to
      visualize the differentiation of effector/memory CD8+ T cells. With this model,
      four major CD8+ T-cell subsets can be easily identified using the combination of
      three markers, CD45RA, CCR7 (CD197), and CD28, with the selection markers CD3,
      CD4, CD8, and side scatter (SSC). PSM enables the translation of complex
      multicolor flow cytometric data to pathway-specific cell subtypes, the capability
      of developing averaged models of healthy donor populations, and the analysis of
      phenotypic heterogeneity. In this report, we also illustrate the heterogeneity in
      memory T-cell subpopulations as branched differentiation markers that include
      CD127, CD62L, CD27, and CD57.

PMID- 23954472
TI  - Nrf2 deficiency induces oxidative stress and promotes RANKL-induced osteoclast
      differentiation.
AB  - Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a redox-sensitive
      transcription factor that regulates the expression of a variety of antioxidant
      and detoxification genes through an antioxidant-response element. Nrf2 has been
      shown to protect several types of cells against the acute and chronic injury that
      accompanies oxidative stress, but its role in osteoclasts remains unclear. In
      this study, we investigated the role of Nrf2 in osteoclast (OC) differentiation,
      a process in which reactive oxygen species (ROS) are generated and then
      participate, using Nrf2-knockout mice. Receptor activator of nuclear factor
      kappaB ligand (RANKL)-induced OC differentiation, actin ring formation, and
      osteoclastic bone resorption were substantially promoted in Nrf2-deficient OC
      precursor cells compared to wild-type cells. Under both unstimulated and RANKL
      stimulated conditions, Nrf2 loss led to an increase in the intracellular ROS
      level and the oxidized-to-reduced glutathione ratio and a defect in the
      production of numerous antioxidant enzymes and glutathione. Moreover,
      pretreatment with N-acetylcysteine or diphenyleneiodonium significantly reduced
      the OC differentiation and decreased the intracellular ROS level in both Nrf2
      deficient and wild-type cells. Pretreatment with sulforaphane and curcumin also
      inhibited the OC differentiation by activating Nrf2 in part. Nrf2 deficiency
      promoted the RANKL-induced activation of mitogen-activated protein kinases,
      including c-Jun N-terminal kinase, extracellular signal-regulated kinase, and
      p38; the induction of c-Fos; and the consequent induction of nuclear factor of
      activated T cells, cytoplasmic 1, a pivotal determinant of OC differentiation.
      Our results suggest that Nrf2 probably inhibits RANKL-induced OC differentiation
      by regulating the cellular redox status by controlling the expression of
      oxidative response genes, findings that might form the basis of a new strategy
      for treating inflammatory bone diseases. 

PMID- 23954474
TI  - Development and evaluation of a sandwich ELISA method for the detection of human
      CD306.
AB  - CD306, also known as soluble leukocyte-associated immunoglobulin-like receptor-2
      (LAIR-2), is a member of an immunoglobulin superfamily with the shared
      characteristic of an immunoglobulin-like C2-type domain. CD306 is speculated to
      be secretory and has 84% similarity with the extracellular domain of CD305, which
      binds to the same ligands as CD306. However, data on its distribution are absent
      due to the lack of an efficient method to detect it. In this study, we
      successfully cloned the cDNA of CD306 from the peripheral blood mononuclear cells
      (PBMCs) of patients with hemorrhagic fever with renal syndrome. The fusion
      proteins were expressed and purified, and three strains of monoclonal antibodies
      (mAbs) against CD306 were prepared and characterized. The sandwich ELISA for
      detecting CD306 was established and optimized with sensitivity up to 15 pg/ml,
      and the assay showed high specificity for the detection of CD306. With this
      method, a right skewed frequency distribution of CD306 in the sera of healthy
      subjects was determined. The concentrations of CD306 in sera and urine were
      detected in patients with different diseases. Aberrantly high levels of CD306
      were found in the sera of pregnant women and patients with inflammation and
      rheumatic heart disease and in the urine of pregnant women. Meanwhile, there was
      a positive correlation between CD306 and soluble CD305 expression and secretion
      levels in sera and urine samples from patients, and both proteins inhibited CD305
      mediated immunosuppressive functions. Our results demonstrate that CD306
      represents a potentially useful predictor for disease diagnosis and that the
      method developed has potential for clinical application.

PMID- 23954475
TI  - Leptin as a marker for severity and prognosis of aneurysmal subarachnoid
      hemorrhage.
AB  - Leptin has been identified as a plasma marker for outcomes in traumatic brain
      injury and intracerebral hemorrhage. We further investigated whether leptin might
      serve as a marker for severity and prognosis in aneurysmal subarachnoid
      hemorrhage. One hundred and eight consecutive patients and 108 sex and age -
      matched healthy subjects were recruited. Plasma leptin levels were measured by
      enzyme-linked immunosorbent assay. Clinical severity was assessed using World
      Federation of Neurological Surgeons score and Fisher score. Mortality and poor
      long-term outcome (Glasgow outcome scale scores of 1-3) at 6 months were
      recorded. Plasma leptin levels on admission were substantially higher in patients
      than in healthy controls, and were significantly associated with the clinical
      severity. There was also a significant association between leptin levels and
      clinical outcomes at 6 months in multivariate logistic regression analysis. Using
      receiver operating characteristic curves, we calculated areas under the curve for
      clinical outcomes at 6 months. The predictive performance of leptin was similar
      to, but did not obviously improve those of World Federation of Neurological
      Surgeons score and Fisher score. Thus, leptin may indicate clinical severity of
      the initial bleeding and also have prognostic value for clinical outcomes in
      aneurysmal subarachnoid hemorrhage and may therefore help in guiding treatment
      decisions in the setting of aneurysmal subarachnoid hemorrhage. 

PMID- 23954476
TI  - Apelin stimulates both cholecystokinin and glucagon-like peptide 1 secretions in
      vitro and in vivo in rodents.
AB  - Apelin is an enteric peptide that exerts several digestive functions such as
      stimulation of cell proliferation and cholecystokinin (CCK) secretion. We
      investigated using murine enteroendocrine cell line (STC-1) and rats if apelin-13
      stimulates both CCK and glucagon-like peptide 1 (GLP-1) secretions. We
      demonstrated that, in vitro and in vivo, apelin-13 increases the release of these
      two hormones in a dose-dependent manner. Present data suggest that apelin may
      modulate digestive functions, food intake behavior and glucose homoeostasis via
      apelin-induced release of enteric CCK but also through a new incretin-releasing
      activity on enteric GLP-1. 

PMID- 23954477
TI  - The D. melanogaster capa-1 neuropeptide activates renal NF-kB signaling.
AB  - The capa peptide family exists in a very wide range of insects including species
      of medical, veterinary and agricultural importance. Capa peptides act via a
      cognate G-protein coupled receptor (capaR) and have a diuretic action on the
      Malpighian tubules of Dipteran and Lepidopteran species. Capa signaling is
      critical for fluid homeostasis and has been associated with desiccation tolerance
      in the fly, Drosophila melanogaster. The mode of capa signaling is highly
      complex, affecting calcium, nitric oxide and cyclic GMP pathways. Such complex
      physiological regulation by cell signaling pathways may occur ultimately for
      optimal organismal stress tolerance to multiple stressors. Here we show that D.
      melanogaster capa-1 (Drome-capa-1) acts via the Nuclear Factor kappa B (NF-kB)
      stress signaling network. Human PCR gene arrays of capaR-transfected Human
      Embryonic Kidney (HEK) 293 cells showed that Drome-capa-1 increases expression of
      NF-kB, NF-kB regulated genes including IL8, TNF and PTGS2, and NF-kB pathway
      associated transcription factors i.e. EGR1, FOS, cJUN. Furthermore, desiccated
      HEK293 cells show increased EGR1, EGR3 and PTGS2 - but not IL8, expression. CapaR
      transfected NF-kB reporter cells showed that Drome-capa-1 increased NF-kB
      promoter activity via increased calcium. In Malpighian tubules, both Drome-capa-1
      stimulation and desiccation result in increased gene expression of the D.
      melanogaster NF-kB orthologue, Relish; as well as EGR-like stripe and klumpfuss.
      Drome-capa-1 also induces Relish translocation in tubule principal cells.
      Targeted knockdown of Relish in only tubule principal cells reduces desiccation
      stress tolerance of adult flies. Together, these data suggest that Drome-capa-1
      acts in desiccation stress tolerance, by activating NF-kB signaling. 

PMID- 23954478
TI  - Mitochondrial DNA polymorphisms in Phytophthora infestans: new haplotypes are
      identified and re-defined by PCR.
AB  - Polymorphisms of mitochondrial DNA (mt-DNA) are particularly useful for
      monitoring specific pathogen populations like Phytophthora infestans. Basically
      type I and II of P. infestans mt-DNA were categorized by means of polymorphism
      lengths caused by an ~2 kb insertion, which can be detected via restriction
      enzyme digestion. In addition genome sequencing of haplotype Ib has been used as
      a simple Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR
      RFLP) method to indirectly identify type I and II alterations through EcoR I
      restriction enzyme DNA fragment patterns of the genomic P4 area. However, with
      the common method, wrong mt-DNA typing occurs due to an EcoR I recognition site
      mutation in the P4 genomic area. Genome sequencing of the four haplotypes (Ia,
      Ib, IIa, and IIb) allowed us to thoroughly examine mt-DNA polymorphisms and we
      indentified two hypervariable regions (HVRs) named HVRi and HVRii. The HVRi
      length polymorphism caused by a 2 kb insertion/deletion was utilized to identify
      mt-DNA types I and II, while another length polymorphism in the HVRii region is
      caused by a variable number of tandem repeats (n = 1, 2, or 3) of a 36 bp sized
      DNA stretch and was further used to determine mt-DNA sub-types, which were
      described as R(n = 1, 2, or 3). Finally, the P. infestans mt-DNA haplotypes were
      re-defined as IR(1) or IIR(2) according to PCR derived HVRi and HVRii length
      polymorphisms. Twenty-three isolates were chosen to verify the feasibility of our
      new approach for identifying mt-DNA haplotypes and a total of five haplotypes
      (IR(1), IR(2), IR(3), IIR(2) and IIR(3)) were identified. Additionally, we found
      that six isolates determined as type I by our method were mistakenly identified
      as type II by the PCR-RFLP technique. In conclusion, we propose a simple and
      rapid PCR method for identification of mt-DNA haplotypes based on sequence
      analyses of the mitochondrial P. infestans genome.

PMID- 23954479
TI  - New cultivation medium for "Ferrovum" and Gallionella-related strains.
AB  - Since the first isolation of the well-known iron oxidizer Acidithiobacillus
      ferrooxidans various media and techniques have been developed to isolate new
      species of acidophilic iron-oxidizing bacteria. A successful strategy in many
      cases was the use of iFeo medium in double-layer plates with a heterotrophic
      strain in the underlayer. However, even with samples which had been shown by
      molecular techniques to be dominated by "Ferrovum myxofaciens" and Gallionella
      related bacteria, these bacteria were isolated considerably less frequently than
      Acidithiobacillus spp. on iFeo. Therefore, a new medium was designed which
      corresponded largely to the chemical composition of the mine water in a treatment
      plant dominated by the bacterial groups mentioned and was called artificial pilot
      plant water (APPW). The analyses of approximately 500 colonies obtained from mine
      waters of two different sampling sites by PCR with primers specific for
      Acidithiobacillus spp., "Ferrovum" spp., Gallionella relatives, and Acidiphilium
      spp. revealed higher abundances of "Ferrovum" spp. and Gallionella relatives on
      the newly designed APPW medium than on iFeo which favored Acidithiobacillus spp.
      Molecular analysis of the colonies obtained indicated the occurrence of at least
      two species of iron-oxidizing bacteria and/or the heterotrophic Acidiphilium spp.
      in most of the colonies. Furthermore, the influence on the isolation of the
      concentrations of iron, phosphate, and ammonium of APPW, in levels of the iFeo
      medium previously described was studied. 

PMID- 23954480
TI  - Copper-64 radiolabelling of the C2A domain of synaptotagmin I using a
      functionalised bis(thiosemicarbazone): A pre- and post-labelling comparison.
AB  - Dysregulation of apoptosis and necrosis is central to many diseases and non
      invasive imaging of cell death is an important clinical objective to stage
      disease or to monitor treatment progress. The C2A domain of rat synaptotagmin I
      binds to phosphatidylserine (PS) exposed during cell death and modification to
      its lysine residues has been shown to disrupt PS binding. Site-specifically
      labelled (99m)Tc(CO)3-C2AcH and (68)Ga-C2Ac have previously been investigated for
      single photon emission computed tomography (SPECT) and positron emission
      tomography (PET) imaging, respectively. We wished to design a (64)Cu-labelled
      counterpart due to the longer half-life of (64)Cu. Since the calcium binding
      sites in C2A may interfere with copper binding we sought a high affinity, fast
      labelling chelator. We synthesised a maleimide functionalised
      bis(thiosemicarbazone), H2ATSE/AMal, for the site-specific copper-64
      radiolabelling of thiol-functionalised C2Ac. When radiolabelling was performed by
      incubation of the ligand-protein conjugate (post-labelling approach), analysis of
      the resultant (64)CuATSE/AMal-C2Ac revealed that the C2Ac was able to compete for
      radiocopper with the chelator. In contrast, the pre-labelled (64)CuATSE/AMal-C2Ac
      conjugate revealed good stability in serum and maintained target affinity in a
      red blood cell binding assay. The results suggest that due to the intrinsic
      copper binding properties of the protein, a pre-labelling approach is preferred
      for the C2Ac domain of synaptotagmin I when copper is the desired radioisotope.

PMID- 23954481
TI  - Determination of stability constants of Cu(I), Cd(II) & Zn(II) complexes with
      thiols using fluorescent probes.
AB  - Fluorometric competing-ligand titrations were used to measure stability constants
      of Zn(II), Cd(II) and Cu(I) complexes of cysteine and glutathione (GSH). Cu(I)
      stability constants were also determined for the dipeptides Arg-Cys and Gln-Cys
      which are produced by a marine alga under copper stress. The fluorescent ion
      indicators FluoZin-1 and BTC (Invitrogen) were used as competing ligands in
      titrations involving Zn(II) and Cd(II). Phen Green SK (Invitrogen) was likewise
      used in Cu(I) titrations. Conditional and cumulative general stability constants
      were determined using a least squares fit of the titration data to speciation
      models. The measured stability constants of Cd(II) and Zn(II) complexes were
      consistent with previous work, validating our method and assumptions. Our results
      also include the first general stability constants for Cu(I)-cysteine complexes
      and an alternative set for Cu(I)-GSH complexes. While these stability constants
      indicate that Cu(I) forms strong complexes with thiols, they are not strong
      enough to effectively buffer Cu(I) in seawater.

PMID- 23954482
TI  - DNA-based aptamer fails as a simultaneous cancer targeting agent and drug
      delivery vehicle for a phenanthroline-based platinum(II) complex.
AB  - The sgc8c aptamer is a 41-base DNA oligonucleotide that binds to leukaemia cells
      with high affinity and specificity. In this work we examined the utility of this
      aptamer as both a delivery vehicle and an active targeting agent for an inert
      platinum complex [(1,10-phenathroline)(ethylenediamine)platinum(II)](2+). The
      aptamer forms a stem-and-loop confirmation as determined by circular dichroism.
      This conformation is adopted in both water and phosphate buffered saline
      solutions. The metal complex binds through intercalation into the aptamer's
      double helical stem with a binding constant of approximately 4.3 * 10(4) M(-1).
      Binding of the metal complex to the aptamer had a significant effect on the
      aptamer's global conformation, and increased its melting temperature by 28
      degrees C possibly through lengthening and stiffening of the aptamer stem. The
      effect of the aptamer on the metal complex's cytotoxicity and cellular uptake was
      determined using in vitro assays with the target leukaemia cell line CCRF-CEM and
      the off-target ovarian cancer cell lines A2780 and A2780cp70. The aptamer has
      little inherent cytotoxicity and when used to deliver the metal complex results
      in a significant decrease in the metal complex's cytotoxicity and uptake. The
      reason(s) for the poor uptake and activity may be due to the change in aptamer
      conformation which affects its ability to recognise leukaemia cells.

PMID- 23954483
TI  - Maxillofacial trauma in the emergency department: a review.
AB  - OBJECTIVES: In 1978 the Advanced Trauma Life Support guidelines were first
      implemented and are viewed by many as the gold standard of care in the emergency
      setting. It may not be immediately obvious where assessment and management of
      maxillofacial injuries fits within these trauma guidelines. This article aims to
      provide a concise, contemporary guide for the treatment of maxillofacial trauma
      in the emergency setting. METHODS: An electronic database search was conducted in
      PubMed and Science Direct on articles from 1970 to the present day. The key
      search terms were Maxillofacial, Trauma, ATLS, Advanced Trauma Life Support,
      EMST, Early Management of Severe Trauma, Airway, Eye, Ophthalmic and Management.
      The findings were compiled into a review article. The article was then reviewed
      by experts in the fields of Maxillofacial Surgery and Ophthalmology to ensure
      content and contextual accuracy. RESULTS: Physicians are becoming increasingly
      exposed to major maxillofacial injuries. Resuscitative measures can be complex
      and require prompt decisions especially in gaining a secure airway. A proposed
      treatment algorithm for maxillofacial trauma patients has been devised by the
      authors. CONCLUSIONS: It is imperative that sight preserving assessment and
      interventions are not forgotten in the emergency management of maxillofacial
      trauma. We propose an algorithm for the management of maxillofacial trauma, and
      recommend the use of CT as a powerful adjunct to clinical examination in patients
      with maxillofacial trauma.

PMID- 23954484
TI  - Prospective slice-by-slice motion correction reduces false positive activations
      in fMRI with task-correlated motion.
AB  - OBJECTIVE: We aimed to test the hypothesis that slice-by-slice prospective motion
      correction at 7T using an optical tracking system reduces the rate of false
      positive activations in an fMRI group study with a paradigm that involves task
      correlated motion. MATERIALS AND METHODS: Brain activation during right leg
      movement was measured using a block design on 15 volunteers, with and without
      prospective motion correction. Clearly erroneous activations were compared
      between both cases, at the individual level. Additionally, conventional group
      analysis was performed. RESULTS: The number of falsely activated voxels with T
      values higher than 5 was reduced by 48% using prospective motion correction
      alone, without additional retrospective realignment. In the group analysis, the
      statistical power was increased - the peak T-value was 26% greater, and the
      number of voxels in the cluster representing the right leg was increased by a
      factor of 9.3. CONCLUSION: Slice-by-slice prospective motion correction in fMRI
      studies with task-correlated motion can substantially reduce false positive
      activations and increase statistical power.

PMID- 23954485
TI  - Altered white matter connectivity and network organization in polymicrogyria
      revealed by individual gyral topology-based analysis.
AB  - Polymicrogyria (PMG) is a cortical malformation characterized by multiple small
      gyri and altered cortical lamination, which may be associated with disrupted
      white matter connectivity. However, little is known about the topological
      patterns of white matter networks in PMG. We examined structural connectivity and
      network topology using individual primary gyral pattern-based nodes in PMG
      patients, overcoming the limitations of an atlas-based approach. Structural
      networks were constructed from structural and diffusion magnetic resonance images
      in 25 typically developing and 14 PMG subjects. The connectivity analysis for
      different fiber groups divided based on gyral topology revealed severely reduced
      connectivity between neighboring primary gyri (short U-fibers) in PMG, which was
      highly correlated with the regional involvement and extent of abnormal gyral
      folding. The patients also showed significantly reduced connectivity between
      distant gyri (long association fibers) and between the two cortical hemispheres.
      In relation to these results, gyral node-based graph theoretical analysis
      revealed significantly altered topological organization of the network (lower
      clustering and higher modularity) and disrupted network hub architecture in
      cortical association areas involved in cognitive and language functions in PMG
      patients. Furthermore, the network segregation in PMG patients decreased with the
      extent of PMG and the degree of language impairment. Our approach provides the
      first detailed findings and interpretations on altered cortical network topology
      in PMG related to abnormal cortical structure and brain function, and shows the
      potential for an individualized method to characterize network properties and
      alterations in connections that are associated with malformations of cortical
      development. 

PMID- 23954486
TI  - Ultra-high resolution imaging of the human brain using acquisition-weighted
      imaging at 9.4T.
AB  - One of the main goals of ultra-high field MRI is to increase the spatial
      resolution reached in structural and functional images. Here, the possibility to
      obtain in vivo images of the human brain with voxel volumes below 0.02mm(3) is
      shown at 9.4T. To optimize SNR and suppress ringing artifacts, an acquisition
      weighted 3D gradient-echo sequence is used, which acquires more averages in the
      center than in the outer regions of k-space. The weighting function is adjusted
      to avoid losses in spatial resolution and scan duration compared to a
      conventional experiment with an equal number of scans and otherwise identical
      parameters. Spatial resolution and SNR of the weighted sequence are compared to
      conventionally acquired images by means of phantom and in vivo measurements, and
      show improved image quality with unchanged spatial resolution and an SNR increase
      of up to 36% in phantoms and 20%+/-5% in vivo. Ultra-high resolution images with
      a voxel volume of 0.014mm(3) (0.13*0.13*0.8mm(3)) from the human brain have
      sufficient SNR and show fine intracortical detail, demonstrating the potential of
      the technique. The combination of acquisition-weighted imaging and highly
      sensitive array coils at ultra-high fields thus makes it possible to obtain
      images with ultra-high spatial resolutions within acceptable scan times. 

PMID- 23954487
TI  - A systematic review of the reporting of sample size calculations and
      corresponding data components in observational functional magnetic resonance
      imaging studies.
AB  - Anecdotal evidence suggests that functional magnetic resonance imaging (fMRI)
      studies rarely consider statistical power when setting a sample size. This raises
      concerns since undersized studies may fail to detect effects of interest and
      encourage data dredging. Although sample size methodology in this field exists,
      implementation requires specifications of estimated effect size and variance
      components. We therefore systematically evaluated how often estimates of effect
      size and variance components were reported in observational fMRI studies
      involving clinical human participants published in six leading journals between
      January 2010 and December 2011. A random sample of 100 eligible articles was
      included in data extraction and analyses. Two independent reviewers assessed the
      reporting of sample size calculations and the data components required to perform
      the calculations in the fMRI literature. One article (1%) reported sample size
      calculations. The reporting of parameter estimates for effect size (8%), between
      subject variance (4%), within-subject variance (1%) and temporal autocorrelation
      matrix (0%) was uncommon. Three articles (3%) reported Cohen's d or F effect
      sizes. The majority (83%) reported peak or average t, z or F statistics. The
      inter-rater agreement was very good, with a prevalence-adjusted bias-adjusted
      kappa (PABAK) value greater than 0.88. We concluded that sample size calculations
      were seldom reported in fMRI studies. Moreover, omission of parameter estimates
      for effect size, between- and within-subject variances, and temporal
      autocorrelation matrix could limit investigators' ability to perform power
      analyses for new studies. We suggest routine reporting of these quantities, and
      recommend strategies for reducing bias in their reported values. 

PMID- 23954488
TI  - BOLD sensitivity and SNR characteristics of parallel imaging-accelerated single
      shot multi-echo EPI for fMRI.
AB  - Echo-planar imaging (EPI) is a standard procedure in functional magnetic
      resonance imaging (fMRI) for measuring changes in the blood oxygen level
      dependent (BOLD) signal associated with neuronal activity. The images obtained
      from fMRI with EPI, however, exhibit signal dropouts and geometric distortions.
      Parallel imaging (PI), due to its short readout, accelerates image acquisition
      and might reduce dephasing in phase-encoding direction. The concomitant loss of
      signal-to-noise ratio (SNR) might be compensated through single-shot multi-echo
      EPI (mEPI). We systematically compared the temporal SNR and BOLD sensitivity of
      single echoes (TE=15, 45, and 75ms) and contrast-optimized mEPI with and without
      PI and mEPI-based denoising. Audio-visual stimulation under natural viewing
      conditions activated distributed neural networks. Heterogeneous SNR, noise gain,
      and sensitivity maps emerged. In single echoes, SNR and BOLD sensitivity followed
      the predicted dependency on echo time (TE) and were reduced under PI. However,
      the combination of echoes with mEPI recovered the quality parameters and
      increased BOLD signal changes at circumscribed fronto-polar and deep brain
      structures. We suggest applying PI only in combination with mEPI to reduce
      imaging artifacts and conserve BOLD sensitivity. 

PMID- 23954489
TI  - Five methodological challenges in cognitive electrophysiology.
AB  - Here we discuss five methodological challenges facing the current cognitive
      electrophysiology literature that address the roles of brain oscillations in
      cognition. The challenges focus on (1) unambiguous and consistent terminology,
      (2) neurophysiologically meaningful interpretations of results, (3) evaluation
      and comparison of different spatial filters often used in M/EEG research, (4) the
      role of multiscale interactions in brain and cognitive function, and (5)
      development of biophysically plausible cognitive models. We also suggest research
      directions that will help address these challenges. We hope that this paper will
      help foster discussions and debates about important themes in the study of how
      the brain's rhythmic patterns of spatiotemporal electrophysiological activity
      support cognition. 

PMID- 23954490
TI  - PET neuroimaging: plenty of studies still need to be performed: comment on
      Cumming: "PET neuroimaging: the white elephant packs his trunk?".

PMID- 23954492
TI  - The phenothiazine-class antipsychotic drugs prochlorperazine and trifluoperazine
      are potent allosteric modulators of the human P2X7 receptor.
AB  - P2X7, an ATP-gated cation channel, is involved in immune cell activation,
      hyperalgesia and neuropathic pain. By regulating cytokine release in the brain,
      P2X7 has been linked to the pathophysiology of mood disorders and schizophrenia.
      We here assess the impact of 123 drugs that act in the central nervous system on
      human P2X7. Most prominently, the tricyclic antipsychotics prochlorperazine (PCP)
      and trifluoperazine (TFP) potently inhibited P2X7-mediated Ca2+ entry, dye
      permeation and ionic currents. In divalent cation-containing bath solutions or
      after prolonged incubation, ATP-evoked P2X7 currents were inhibited by 10 MUM
      PCP. This effect was not related to dopamine receptor antagonism. Surprisingly,
      PCP co-applied with ATP enhanced inward currents in bath solutions with low
      divalent cation concentrations. Intracellular perfusion with PCP did not
      substitute for the extracellularly applied drug, indicating that its binding
      sites are accessible from the extracellular space. Since P2X7 current
      potentiation by PCP was voltage-dependent, at least one site may be located
      within the electrical field of the membrane. While the channel opening and
      closure kinetic was altered by PCP, the apparent affinity of ATP remained
      unchanged (potentiation) or changed slightly (inhibition). Measurements in human
      monocyte-derived macrophages confirmed the PCP-induced inhibition of ATP-evoked
      Ca2+ influx, Yo-Pro-1 permeability, and whole cell currents. Interestingly,
      neither heterologously expressed rat or mouse P2X7 nor native P2X7 in rat
      astrocyte cultures or in mouse bone marrow-derived macrophages were inhibited by
      perazines with a similar potency. We conclude that perazine-type neuroleptics are
      potent, but species-selective allosteric modulators of human but not murine P2X7
      receptors.

PMID- 23954491
TI  - Trajectory of adolescent cannabis use on addiction vulnerability.
AB  - The adolescent brain is a period of dynamic development making it vulnerable to
      environmental factors such as drug exposure. Of the illicit drugs, cannabis is
      most used by teenagers since it is perceived by many to be of little harm. This
      perception has led to a growing number of states approving its legalization and
      increased accessibility. Most of the debates and ensuing policies regarding
      cannabis were done without consideration of its impact on one of the most
      vulnerable population, namely teens, or without consideration of scientific data.
      We provide an overview of the endocannabinoid system in relation to adolescent
      cannabis exposure and provide insights regarding factors such as genetics and
      behavioral traits that confer risk for subsequent addiction. While it is clear
      that more systematic scientific studies are needed to understand the long-term
      impact of adolescent cannabis exposure on brain and behavior, the current
      evidence suggests that it has a far-reaching influence on adult addictive
      behaviors particularly for certain subsets of vulnerable individuals. This
      article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

PMID- 23954493
TI  - Bidirectional modulatory effect of 17beta-estradiol on NMDA receptors via ERalpha
      and ERbeta in the dentate gyrus of juvenile male rats.
AB  - The neurosteroid 17beta-estradiol (E2) is synthesized by aromatase in both male
      and female hippocampi and is known to modulate hippocampal synaptic functions.
      However, as some contradictory findings regarding the modulatory effects of E2
      have been reported in the literature, its physiological role and mechanism of
      action in the hippocampus remain controversial. Our recent study showed that a
      low E2 dose (1 nM) increased the amplitude of NMDA receptor-mediated EPSCs (NMDAR
      EPSCs) and lowered the threshold for the induction of NMDA receptor-dependent
      long-term potentiation (NMDAR-LTP), while a high E2 dose (7 nM) exerted opposite
      effects in the dentate gyrus of juvenile male rat hippocampal slices. The present
      study is a follow-up that explores the underlying mechanism of this bidirectional
      effect of E2. We found that the ERalpha agonist PPT reproduced the actions of the
      low E2 dose on NMDAR-EPSCs and NMDAR-LTP, while the ERbeta agonist DPN reproduced
      the actions of the high E2 dose. Moreover, PPT, but not DPN, restored the
      decrease in NMDAR-EPSCs induced by the aromatase inhibitor letrozole, suggesting
      that E2 synthesized constitutively in the hippocampus enhances NMDA receptor
      function via ERalpha. The PPT-induced enhancement in NMDAR-EPSCs was mediated by
      Src family kinase, but was not caused by NR2B modulation. These findings
      demonstrate that E2 exerts condition-dependent bidirectional effects on NMDA
      receptor-mediated transmission and, thus, synaptic plasticity via ERalpha and
      ERbeta in the dentate gyrus of juvenile male rats. 

PMID- 23954494
TI  - Canine echinococcosis: global epidemiology and genotypic diversity.
AB  - Canine echinococcosis is a potential zoonotic infection caused by the adult form
      of several cestode species belonging to the genus Echinococcus, of which E.
      granulosus sensu lato and E. multilocularis are the most epidemiologically
      relevant. Dogs infected with E. granulosus and E. multilocularis are widely
      regarded as the main source of infection for human cystic and alveolar
      echinococcosis, diseases that cause substantial morbidity and socio-economic
      burden in several regions of the world. Following our previous review on the
      global situation of cystic echinococcosis in livestock species (Cardona and
      Carmena. Vet. Parasitol. 2013;192:10-32), we summarize here current knowledge on
      the global epidemiology, geographical distribution and molecular diversity of
      Echinococcus spp. infection in dogs. We address relevant topics including the
      implications of the increasing urbanization of wildlife species such as foxes,
      coyotes, and dingoes in the establishment of urban cycles of Echinococcus spp.,
      or the rising concerns regarding the role of unsupervised translocation of
      infected dogs in spreading the infection to Echinococcus-free areas. The
      involvement of wildlife species as natural reservoirs of disease to domestic
      animals and humans and the epidemiological significance of the sympatric
      occurrence of different Echinococcus species in the same geographical region are
      also debated. Data presented are expected to be useful for policy makers,
      educational and health authorities responsible for designing and implementing
      effective measures for disease control and prevention. 

PMID- 23954495
TI  - Application of scanning thermal microscopy for investigation of thermal
      boundaries in multilayered photonic structures.
AB  - In current work the application of modified Scanning Thermal Microscopy (SThM)
      technique for thermal imaging of multilayered periodic photonic structures is
      presented. The measurements were carried out using non-standard operation mode of
      the SThM. The thermal probe was driven by the sum of DC and small AC currents.
      The main advantages of presented approach are mechanical stability of the probe
      during measurements and high sensitivity of AC signal detection by the use of
      lock-in amplifier. The amplitude and phase components of probe response signal
      are used for visualization and analysis of the thermal properties of the layer
      interfaces. Basing on topographic and thermal signals the thermal boundaries
      between layers were revealed and the periodicity of the structure was analyzed.
      Presented experiment indicates that the proposed method provides spatial
      resolution at least about 30% better than 100 nm, which is considered for
      standard nanofabricated thermal probes. Therefore, proposed technique may be
      successfully used for the thermal boundaries mapping, as well as for the high
      resolution nanoscale imaging of thermal properties distribution. The results
      prove that thermal imaging provides additional information to that obtained by
      standard AFM imaging.

PMID- 23954496
TI  - Nanofabrication of a gold fiducial array on specimen support for electron
      tomography.
AB  - Here we describe the production, using lithography and micro-engineering
      technologies, of patterned arrays of nanofabricated gold dots on a thin Si3N4
      electron transparent layer, supported by silicon. We illustrate that the support
      with a patterned structure of nanosized gold can be exploited for (cryo) electron
      tomography application as a specimen support with predefined alignment markers.
      This nanogold patterned support has several advantages. The Si3N4 window provides
      a 50 nm thin, strong and flat support with a ~0.7 mm(2) large electron-beam
      transparent window. The nanogold pattern has a user-defined size and density, is
      highly regular and stable. This facilitates accurate tracking during tilt series
      acquisition, provides sufficient contrast for accurate alignment during the image
      reconstruction step and avoids an uneven lateral distribution and movement of
      individual fiducials. We showed that the support is suitable for electron
      tomography on plastic sections.

PMID- 23954497
TI  - The affective dimension of dyspnea improves in a dyspnea self-management program
      with exercise training.
AB  - CONTEXT: The perception of dyspnea includes both sensory and affective dimensions
      that are shaped by emotions and psychological, social, and environmental
      experiences. Previous investigators have studied either measurement or strategies
      to decrease the affective dimension with laboratory-induced dyspnea. Few have
      reported the effect of a therapeutic clinical intervention on the affective
      dimension of dyspnea. OBJECTIVES: (1) To evaluate the effects of three different
      versions of a dyspnea self-management program (DM) on the affective dimension of
      dyspnea, measured by dyspnea-related anxiety (DA) and dyspnea-related distress
      (DD); and (2) to determine the stability of DA and DD over two baseline
      incremental treadmill tests (ITTs). METHODS: Participants with chronic
      obstructive pulmonary disease were randomly assigned to three 12 month DMs with
      varying doses of supervised exercise (DM, DM-Exposure, and DM-Training). The
      measurements of the affective dimension, DA and DD, were rated during ITTs on two
      baseline days and at two, six, and 12 months. Changes over time in DA and DD were
      analyzed using linear mixed-effects models. RESULTS: Participants in the DM
      Training group who received 24 nurse-coached exercise sessions had significantly
      greater reductions in DA and DD compared with those who had four exercise
      sessions (DM-Exposure) or only received a home-walking program (DM). Reductions
      in DA and DD in the DM-Training group were only maintained through six months.
      There were no significant differences in ratings of DA and DD at end between the
      two baseline ITTs. CONCLUSION: These findings provide initial support for the
      positive impact of a self-management program with nurse-coached exercise on the
      affective dimension of dyspnea. Further investigation of interventions that
      target the affective dimension in addition to the sensory dimension of dyspnea
      should be encouraged.

PMID- 23954498
TI  - Comparison of label-free and label-based strategies for proteome analysis of
      hepatoma cell lines.
AB  - Within the past decade numerous methods for quantitative proteome analysis have
      been developed of which all exhibit particular advantages and disadvantages.
      Here, we present the results of a study aiming for a comprehensive comparison of
      ion-intensity based label-free proteomics and two label-based approaches using
      isobaric tags incorporated at the peptide and protein levels, respectively. As
      model system for our quantitative analysis we used the three hepatoma cell lines
      HepG2, Hep3B and SK-Hep-1. Four biological replicates of each cell line were
      quantitatively analyzed using an RPLC-MS/MS setup. Each quantification experiment
      was performed twice to determine technical variances of the different
      quantification techniques. We were able to show that the label-free approach by
      far outperforms both TMT methods regarding proteome coverage, as up to threefold
      more proteins were reproducibly identified in replicate measurements.
      Furthermore, we could demonstrate that all three methods show comparable
      reproducibility concerning protein quantification, but slightly differ in terms
      of accuracy. Here, label-free was found to be less accurate than both TMT
      approaches. It was also observed that the introduction of TMT labels at the
      protein level reduces the effect of underestimation of protein ratios, which is
      commonly monitored in case of TMT peptide labeling. Previously reported
      differences in protein expression between the particular cell lines were
      furthermore reproduced, which confirms the applicability of each investigated
      quantification method to study proteomic differences in such biological systems.
      This article is part of a Special Issue entitled: Biomarkers: A Proteomic
      Challenge.

PMID- 23954499
TI  - 1,3-Diethylurea-enhanced Mg-ATPase activity of skeletal muscle myosin with a
      converse effect on the sliding motility.
AB  - We investigate the effects of urea and its derivatives on the ATPase activity and
      on the in vitro motility of chicken skeletal muscle actomyosin. Mg-ATPase rate of
      myosin subfragment-1 (S1) is increased by 4-fold by 0.3M 1,3-diethylurea (DEU),
      but it is unaffected by urea, thiourea, and 1,3-dimethylurea at <=1M
      concentration. Thus, we further examine the effects of DEU in comparison to those
      of urea as reference. In in vitro motility assay, we find that in the presence of
      0.3M DEU, the sliding speeds of actin filaments driven by myosin and heavy
      meromyosin (HMM) are significantly decreased to 1/16 and 1/6.6, respectively,
      compared with the controls. However, the measurement of the actin-activated
      ATPase activity of HMM shows that the maximal rate, Vmax, is almost unchanged
      with DEU. Thus, the myosin-driven sliding motility of actin filaments is
      significantly impeded in the presence of 0.3M DEU, whereas the cyclic interaction
      of myosin with F-actin occurs during the ATP turnover, the rate of which is close
      to that without DEU. In contrast to DEU, 0.3M urea exhibits only modest effects
      on both actin-activated ATPase and sliding motility of actomyosin. Thus, DEU has
      the effect of uncoupling the sliding motility of actomyosin from its ATP
      turnover. 

PMID- 23954500
TI  - Intravaginal prasterone (DHEA) provides local action without clinically
      significant changes in serum concentrations of estrogens or androgens.
AB  - In order to avoid the risks of non-physiological systemic exposure, serum
      concentrations of estradiol (E2) and testosterone (as measured by mass
      spectrometry-based assays) should remain below the 95th centiles measured at
      9.3pg/ml and 0.26ng/ml for these respective sex steroids in normal postmenopausal
      women. To document the possibility of achieving this therapeutic objective, we
      have measured individual 24h serum E2 and testosterone concentrations in women
      with vulvovaginal atrophy (VVA) receiving daily intravaginal administration of a
      clinically effective dose of 6.5mg prasterone (dehydroepiandrosterone, DHEA).
      Serum E2 and testosterone, as well as DHEA and nine of its other metabolites,
      were assayed at ten time intervals over 24h on the first and seventh days of
      daily vaginal administration of 6.5mg prasterone. No significant change from
      baseline of average 24h serum E2 or testosterone concentrations was observed.
      Moreover, average 24h serum DHEA remained within the normal postmenopausal range.
      Estrone sulfate and the androgen metabolites androsterone glucuronide and
      androstane-3alpha, 17beta-diol glucuronide did not change, thus confirming the
      absence of any biologically relevant systemic exposure to estrogens and
      androgens, respectively. Serum concentrations of metabolites of both estrogens
      and androgens remain within the normal postmenopausal range following daily
      intravaginal administration of 6.5mg prasterone. As other studies have shown,
      local formation of sex steroids in peripheral tissues without significant release
      of E2 or testosterone in the circulation can be achieved with intravaginal
      prasterone. Thus, prasterone is a promising physiological and attractive solution
      to treating VVA symptoms. 

PMID- 23954501
TI  - Potency of progestogens used in hormonal therapy: toward understanding
      differential actions.
AB  - Progestogens are widely used in contraception and in hormone therapy. Biochemical
      and molecular biological evidence suggests that progestogens differ widely in
      their affinities and transcriptional effects via different steroid receptors, and
      hence cannot be considered as a single class of compounds. Consistent with these
      observations, recent clinical evidence suggests that, despite their similar
      progestogenic actions, these differences underlie different side-effect profiles
      for cardiovascular disease and susceptibility to infectious diseases. However,
      choice of progestogen for maximal benefit and minimal side-effects is hampered by
      insufficient comparative clinical and molecular studies to understand their
      relative mechanisms of action, as well as their relative potencies for different
      assays and clinical effects. This review evaluates the usage, meaning and
      significance of the terms affinity, potency and efficacy in different models
      systems, with a view to improved understanding of their physiological and
      pharmacological significance. This article is part of a Special Issue entitled
      'Menopause'. 

PMID- 23954503
TI  - Protein interfaces of the conserved Nup84 complex from Chaetomium thermophilum
      shown by crosslinking mass spectrometry and electron microscopy.
AB  - A key building block of the nuclear pore complex (NPC) is the Nup84 subcomplex
      that has been structurally analyzed predominantly in the yeast system. To expand
      this analysis and gain insight into the evolutionary conservation of its
      structure, we reconstituted an octameric Nup84 complex using the subunits from a
      thermophile, Chaetomium thermophilum (ct). This assembly carries Nup37 and Elys,
      which are characteristic subunits of the orthologous human Nup107-Nup160 complex
      but absent from the yeast Saccharomyces cerevisiae. We found that Elys binds
      cooperatively to the complex requiring both Nup37 and Nup120. Unexpectedly, the
      reconstituted ctNup84 complex formed a striking dimer structure with an
      unpredicted side-to-side arrangement of two molecules. Finally, crosslinking mass
      spectrometry allowed the mapping of key protein interfaces within the Y-shaped
      complex. Thus, the thermophilic Nup84 complex can serve as a structural model for
      higher eukaryotic Nup107-Nup160 assemblies to gain insight into its possible
      configuration within the NPC scaffold.

PMID- 23954502
TI  - Structural rearrangement in an RsmA/CsrA ortholog of Pseudomonas aeruginosa
      creates a dimeric RNA-binding protein, RsmN.
AB  - In bacteria, the highly conserved RsmA/CsrA family of RNA-binding proteins
      functions as global posttranscriptional regulators acting on mRNA translation and
      stability. Through phenotypic complementation of an rsmA mutant in Pseudomonas
      aeruginosa, we discovered a family member, termed RsmN. Elucidation of the RsmN
      crystal structure and that of the complex with a hairpin from the sRNA, RsmZ,
      reveals a uniquely inserted alpha helix, which redirects the polypeptide chain to
      form a distinctly different protein fold to the domain-swapped dimeric structure
      of RsmA homologs. The overall beta sheet structure required for RNA recognition
      is, however, preserved with compensatory sequence and structure differences,
      allowing the RsmN dimer to target binding motifs in both structured hairpin loops
      and flexible disordered RNAs. Phylogenetic analysis indicates that, although RsmN
      appears unique to P. aeruginosa, homologous proteins with the inserted alpha
      helix are more widespread and arose as a consequence of a gene duplication event.

PMID- 23954504
TI  - Structural basis of a rationally rewired protein-protein interface critical to
      bacterial signaling.
AB  - Two-component signal transduction systems typically involve a sensor histidine
      kinase that specifically phosphorylates a single, cognate response regulator.
      This protein-protein interaction relies on molecular recognition via a small set
      of residues in each protein. To better understand how these residues determine
      the specificity of kinase-substrate interactions, we rationally rewired the
      interaction interface of a Thermotoga maritima two-component system, HK853-RR468,
      to match that found in a different two-component system, Escherichia coli PhoR
      PhoB. The rewired proteins interacted robustly with each other, but no longer
      interacted with the parent proteins. Analysis of the crystal structures of the
      wild-type and mutant protein complexes and a systematic mutagenesis study reveal
      how individual mutations contribute to the rewiring of interaction specificity.
      Our approach and conclusions have implications for studies of other protein
      protein interactions and protein evolution and for the design of novel protein
      interfaces.

PMID- 23954506
TI  - Altered distribution of bone matrix proteins and defective bone mineralization in
      klotho-deficient mice.
AB  - In an attempt to identify the histological properties of the klotho-deficient
      (kl/kl) bone matrix, bone mineralization and the localization of Ca(2+)-binding
      bone matrix proteins - osteocalcin, dentin matrix protein-1 (DMP-1) and matrix
      Gla protein (MGP) - were examined in kl/kl tibiae. While a widespread osteocalcin
      staining could be verified in the wild-type bone matrix, localization of the same
      protein in the kl/kl tibiae seemed rather restricted to osteocytes with only a
      faint staining of the whole bone matrix. In wild-type mice, MGP immunoreactivity
      was present at the junction between the epiphyseal bone and cartilage, and at the
      insertion of the cruciate ligaments. In kl/kl mice, however, MGP was seen around
      the cartilaginous cores of the metaphyseal trabeculae and in the periphery of
      some cells of the bone surface. DMP-1 was identified in the osteocytic
      canalicular system of wild-type tibiae, but in the kl/kl tibiae this protein was
      mostly found in the osteocytic lacunae and in the periphery of some cells of the
      bone surface. Mineralization of the kl/kl bone seemed somewhat defective, with
      broad unmineralized areas within its matrix. In these areas, mineralized
      osteocytes along with their lacunae and osteocytic cytoplasmic processes were
      found to have intense osteocalcin and DMP-1 staining. Taken together, it might be
      that the excessive production of Ca(2+)-binding molecules such as osteocalcin and
      DMP-1 by osteocytes concentrates mineralization around such cells, disturbing the
      completeness of mineralization in the kl/kl bone matrix. 

PMID- 23954505
TI  - Hexamers of the type II secretion ATPase GspE from Vibrio cholerae with increased
      ATPase activity.
AB  - The type II secretion system (T2SS), a multiprotein machinery spanning two
      membranes in Gram-negative bacteria, is responsible for the secretion of folded
      proteins from the periplasm across the outer membrane. The critical multidomain
      T2SS assembly ATPase GspE(EpsE) had not been structurally characterized as a
      hexamer. Here, four hexamers of Vibrio cholerae GspE(EpsE) are obtained when
      fused to Hcp1 as an assistant hexamer, as shown with native mass spectrometry.
      The enzymatic activity of the GspE(EpsE)-Hcp1 fusions is ~20 times higher than
      that of a GspE(EpsE) monomer, indicating that increasing the local concentration
      of GspE(EpsE) by the fusion strategy was successful. Crystal structures of
      GspE(EpsE)-Hcp1 fusions with different linker lengths reveal regular and
      elongated hexamers of GspE(EpsE) with major differences in domain orientation
      within subunits, and in subunit assembly. SAXS studies on GspE(EpsE)-Hcp1 fusions
      suggest that even further variability in GspE(EpsE) hexamer architecture is
      likely.

PMID- 23954507
TI  - Acute exposure to high dose gamma-radiation results in transient activation of
      bone lining cells.
AB  - The present studies investigated the cellular mechanisms for the detrimental
      effects of high dose whole body gamma-irradiation on bone. In addition,
      radioadaptation and bone marrow transplantation were assessed as interventions to
      mitigate the skeletal complications of irradiation. Increased trabecular
      thickness and separation and reduced cancellous bone volume fraction,
      connectivity density, and trabecular number were detected in proximal tibia and
      lumbar vertebra 14days following gamma-irradiation with 6Gy. To establish the
      cellular mechanism for the architectural changes, vertebrae were analyzed by
      histomorphometry 1, 3, and 14days following irradiation. Marrow cell density
      decreased within 1day (67% reduction, p<0.0001), reached a minimum value after
      3days (86% reduction, p<0.0001), and partially rebounded by 14days (30%
      reduction, p=0.0025) following irradiation. In contrast, osteoblast-lined bone
      perimeter was increased by 290% (1day, p=0.04), 1230% (3days, p<0.0001), and 530%
      (14days, p=0.003), respectively. There was a strong association between radiation
      induced marrow cell death and activation of bone lining cells to express the
      osteoblast phenotype (Pearson correlation -0.85, p<0.0001). An increase (p=0.004)
      in osteoclast-lined bone perimeter was also detected with irradiation. A priming
      dose of gamma-radiation (0.5mGy), previously shown to reduce mortality, had
      minimal effect on the cellular responses to radiation and did not prevent
      detrimental changes in bone architecture. Bone marrow transplantation normalized
      marrow cell density, bone turnover, and most indices of bone architecture
      following irradiation. In summary, radiation-induced death of marrow cells is
      associated with 1) a transient increase in bone formation due, at least in part,
      to activation of bone lining cells, and 2) an increase in bone resorption due to
      increased osteoclast perimeter. Bone marrow transplantation is effective in
      mitigating the detrimental effects of acute exposure to high dose whole body
      gamma-radiation on bone turnover. 

PMID- 23954508
TI  - Are in situ formulations the keys for the therapeutic future of S-nitrosothiols?
AB  - S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) were
      formulated into in situ forming implants (ISI) and microparticles (ISM) using
      PLGA and either N-methyl-2-pyrrolidone (NMP) or triacetin. Physicochemical
      characterization was carried out, including the study of matrix structure and
      degradation. A strong correlation between drug hydrophobicity and the in vitro
      release profiles was observed: whatever the formulation, GSNO and SNAP were
      completely released after ca. 1 day and 1 week, respectively. Then, selected
      formulations (i.e., SNAP-loaded NMP formulations) demonstrated the ability to
      sustain the vasodilation effect of SNAP, as shown by monitoring the arterial
      pressure (telemetry) of Wistar rats after subcutaneous injection. Both ISI and
      ISM injections resulted in a 3-fold extended decrease in pulse arterial pressure
      compared with the unloaded drug, without significant decrease in the mean
      arterial pressure. Hence, the results emphasize the suitability of these
      formulations as drug delivery systems for S-nitrosothiols, widening their
      therapeutic potential.

PMID- 23954509
TI  - Poly-L-asparagine nanocapsules as anticancer drug delivery vehicles.
AB  - This work presents for the first time the development of novel poly-L-asparagine
      (PASN) nanocapsules and the in vitro evaluation of their potential as anticancer
      drug delivery systems. The design of PASN nanocapsules was inspired by the well
      known avidity of cancer cells for the amino acid L-asparagine together with the
      expected ability of this hydrophilic polymer to escape to the mononuclear
      phagocytic system. Besides, these nanocapsules have an oily reservoir, which
      enables the efficient encapsulation of lipophilic drugs. PASN nanocapsules were
      obtained by an emulsification-polymer layer deposition process, which involves
      using a cationic surfactant as a bridge for the interaction of PASN with the
      lipid core. PASN nanocapsules showed sizes of around 170-200 nm and negative zeta
      potential values (around -20 mV to -40 mV). The model anticancer drug docetaxel
      was efficiently encapsulated (around 75%) and retained within the nanocapsule's
      structure upon dilution in a simulated physiological medium. Moreover, these
      nanocapsules exhibited the ability to interact with the NCI-H460 human cancer
      cells and to enhance the cellular toxicity of the anticancer drug. All these
      features together with their adequate stability profile render these nanocapsules
      a new attractive platform for anticancer intracellular drug delivery.

PMID- 23954510
TI  - Inclusion of fenofibrate in a series of mesoporous silicas using microwave
      irradiation.
AB  - A selection of porous silicas were combined with a model drug using a recently
      developed, controlled microwave heating process to determine if the application
      of microwave irradiation could enhance subsequent drug release. Five mesoporous
      silica types were investigated (core shell, core shell rehydrox, SBA-15, silica
      gel, SYLOID(r)) and, for comparison, one non-porous silica (stober). These were
      formulated using a tailored microwave heating method at drug/excipient ratios of
      1:1, 1:3 and 1:5. In addition, all experiments were performed both in the
      presence and absence of water, used as a fluidising media to aid interaction
      between drug and support, and compared with results obtained using more
      traditional heating methods. All formulations were then characterised using
      differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), scanning
      electron microscopy (SEM) and Fourier transformation infrared spectroscopy (FT
      IR). Pharmaceutical performance was investigated using in vitro drug release
      studies. A significant enhancement in the release profile of fenofibrate was
      observed for formulations prepared using microwave heating in the absence of
      water for five of the six silica based formulations. Of all the formulations
      analysed, the greatest extent of drug release within the experimental 30 min was
      the 1:5 core shell rehydrox achieving a total of 86.6 +/- 2.8%. The non-porous
      (stober) particles did not exhibit an increased release of the drug under any
      experimental conditions studied. This anomaly is thought to be a result of the
      comparatively small surface area of the silica particles, thus preventing the
      adsorption of drug molecules.

PMID- 23954511
TI  - Supersaturated polymeric micelles for oral cyclosporine A delivery.
AB  - Polymeric micelles provide a promising platform for improving oral absorption of
      poorly soluble drugs. However, improved understanding of how drug retention
      within the hydrophobic micelle core can reduce drug absorption is required. We
      designed supersaturated polymeric micelles (Super-PMs) to increase molecularly
      dissolved drug concentration and gain an insight into the effect of the degree of
      supersaturation on oral absorption of cyclosporine A (CsA) in rats. The drug
      release from Super-PMs increased with an increase in initial supersaturation
      degrees in micelles. The cellular uptake of coumarin-6 was reduced by the
      retention of drug in polymer micelles. The transport flux of CsA across Caco-2
      monolayer was increased with initial supersaturation degrees of 0.81-3.53 (p <
      0.05). However, increase in supersaturation to 5.64 actually resulted in
      decreased CsA transport. The same trend was observed in a rat in vivo absorption
      study, in which the highest bioavailability of 134.6 +/- 24.7% (relative to a
      commercial product, Sandimmun Neoral(r), p<0.01) was achieved when the
      supersaturation degree was 3.53. These results demonstrated that Super-PMs were a
      promising drug delivery system for compounds with low aqueous solubility. This
      study also provided an experimental proof for the hypothesis that moderately
      supersaturated formulations are valuable alternative to high supersaturation
      formulations, resulting in optimal in vivo performance, and the degree of
      supersaturation should be carefully controlled to optimize drug absorption.

PMID- 23954513
TI  - Analysis of the action of gymnodimine-A and 13-desmethyl spirolide C on the mouse
      neuromuscular system in vivo.
AB  - Gymnodimine-A and 13-desmethyl spirolide C are marine toxins belonging to the
      cyclic imine group produced by Karenia selliformis and Alexandrium
      ostenfeldii/peruvianum dinoflagellates, respectively. The aim of this work was to
      analyze the pharmacological properties of both toxins (at sub-lethal doses) on
      neuromuscular excitability, when injected locally to isoflurane-anesthetized
      mice, using a multimodal minimally-invasive in vivo electrophysiological
      approach. The main effect of both toxins was a marked reversible time- and dose
      dependent decrease of the compound muscle action potential recorded from the tail
      muscle in response to caudal motor nerve stimulation. The dose-response curves of
      gymnodimine-A and 13-desmethyl spirolide C effect on the maximal amplitude of
      compound muscle action potential revealed 50% inhibitory doses of 51 ng/mouse
      (i.e. 1.6 MUg/kg or 3.3 nmol/kg mouse) and 0.18 ng/mouse (i.e. 6 ng/kg or 0.01
      nmol/kg mouse), respectively. The blocking effect occurred without significant
      modification of motor nerve excitability parameters. It is concluded that the
      inhibition of the mouse compound muscle action potential, induced by gymnodimine
      A and 13-desmethyl spirolide C, results from an action of these toxins at the
      level of the skeletal neuromuscular junction, since both cyclic imine toxins are
      known to interact and block muscle-type nicotinic acetylcholine receptors. In the
      present in vivo study, 13-desmethyl spirolide C was about 300 fold more active
      than gymnodimine-A on equimolar basis. The present in vivo approach, associated
      to recent progress in chemical synthesis of cyclic imine toxins, paves the way
      for more detailed structure-activity studies to obtain new and more potent
      synthetic analogs.

PMID- 23954512
TI  - Botulinum neurotoxin A2 reduces incidence of seizures in mouse models of temporal
      lobe epilepsy.
AB  - Temporal lobe epilepsy often shows pharmacoresistance, and well-known anti
      convulsants sometimes are not effective for blocking chronic seizures. Botulinum
      neurotoxins are metalloproteases that act on presynaptic proteins and inhibit
      neurotransmitter release in both the peripheral and central nerve systems. That
      is why neurotoxins may elicit an effect for the restraint of the seizures.
      Meanwhile, it has been suggested that a property and the stability of neurotoxin
      activities differ among the types A-G, in which type A neurotoxin (ANTX) is,
      especially, the most stable and can continue having activity for a long term. The
      present study therefore investigated the effects of hippocampal injections of
      A2NTX on seizures derived in TLE model mice, received repeated kindling
      stimulations in the amygdala. The injections induced complete disappearance of
      grand mal seizures in half of the population of amygdala kindled mice for 4 days.
      The injections also induced reduction of the evoked seizure level significantly
      for at least 18 days after injections. Taken together, these results suggest that
      A2NTX prevents from epileptic seizures, proposing that A2NTX is available as a
      new antiepileptic reagent. 

PMID- 23954514
TI  - Structure of novel enzyme in mannan biodegradation process 4-O-beta-D-mannosyl-D
      glucose phosphorylase MGP.
AB  - The crystal structure of a novel component of the mannan biodegradation system, 4
      O-beta-D-mannosyl-D-glucose phosphorylase (MGP), was determined to a 1.68-A
      resolution. The structure of the enzyme revealed a unique homohexameric
      structure, which was formed by using two helices attached to the N-terminus and C
      terminus as a tab for sticking between subunits. The structures of MGP complexes
      with genuine substrates, 4-O-beta-D-mannosyl-D-glucose and phosphate, and the
      product D-mannose-1-phosphate were also determined. The complex structures
      revealed that the invariant residue Asp131, which is supposed to be the general
      acid/base, did not exist close to the glycosidic Glc-O4 atom, which should be
      protonated in the catalytic reaction. Also, no solvent molecule that might
      mediate a proton transfer from Asp131 was observed in the substrate complex
      structure, suggesting that the catalytic mechanism of MGP is different from those
      of known disaccharide phosphorylases.

PMID- 23954515
TI  - Assessing the mammalian toxicity of high-boiling point petroleum substances.

PMID- 23954516
TI  - Integrative commentary: implications of blunted reactivity.
AB  - The previous issue of the International Journal of Psychophysiology was a special
      issue that collected some of the latest emerging evidence on blunted reactivity
      and its relationships with a variety of negative health outcomes. This commentary
      on the special issue briefly reviews each of the contributions and then provides
      some thoughts on the general themes that run through these papers. The findings
      from the special issue suggest that both lower and higher than expected
      cardiovascular and neuroendocrine responses to active psychological challenges
      may be maladaptive and differentially associated with adverse health sequelae. 

PMID- 23954517
TI  - Targeting of ADAMTS5's ancillary domain with the recombinant mAb CRB0017
      ameliorates disease progression in a spontaneous murine model of osteoarthritis.
AB  - OBJECTIVE: ADAMTS5 (aggrecanase-2) has been demonstrated to be crucial in the
      development of osteoarthritis (OA), by use of several mouse mutants carrying
      either truncated, catalytically inactive enzymes or aggrecanase-resistant mutant
      aggrecan. We have selected recombinant monoclonal antibodies directed against
      ADAMTS5, by using Intracellular Antibody Capture Technology (IACT). CRB0017
      revealed very high affinity for the enzyme in Biacore analyses and very good
      specificity in a panel of binding assays. Therefore, we tested CRB0017 in a
      relevant spontaneous OA model, the STR/ort mouse. DESIGN: STR/ort male mice were
      recruited at 5 months of age, and treated intra-articularly in each knee with
      CRB0017 1.2 MUg, CRB0017 12 MUg, or vehicle. After 6 weeks, the intra-articular
      administration of CRB0017 was repeated with the same doses. After 3 months from
      recruitment, the animals were sacrificed and the femorotibial joints processed
      for histology and scored in a blind fashion according to both Mankin's and the
      OARSI methods. RESULTS AND CONCLUSIONS: All histological scores were
      significantly decreased in the CRB0017 12 MUg/knee group compared to vehicle,
      while administration of CRB0017 1.2 MUg was associated with a trend to a decrease
      in the same parameters. Therefore, CRB0017 administered twice in 3 months could
      modify the course of OA in the STR/ort mouse, by delaying cartilage breakdown as
      assessed histologically. The procedure of blind scoring of the histological
      samples clearly showed that knee intra-articular administration of CRB0017, an
      anti-ADAMTS5 antibody, dose-dependently improved disease progression in a
      relevant animal model of OA.

PMID- 23954518
TI  - Levetiracetam interacts synergistically with nonsteroidal analgesics and caffeine
      to produce antihyperalgesia in rats.
AB  - Levetiracetam is a novel anticonvulsant with antihyperalgesic efficacy in
      inflammatory pain. Nonsteroidal analgesics and caffeine, as analgesic adjuvant,
      are widely used against inflammatory pain. This study characterized the manner in
      which levetiracetam interacts with analgesics (ibuprofen, celecoxib, and
      paracetamol) and caffeine to suppress hyperalgesia in a model of localized
      inflammation. Rat paw inflammation was induced by intraplantar carrageenan (.1
      mL, 1%). Hyperalgesia and antihyperalgesic effects of levetiracetam (orally),
      analgesics (orally), and caffeine (intraperitoneally) alone and 2-drug
      combinations of levetiracetam with analgesics or caffeine were examined by a
      modified paw pressure test. The type of interaction between components was
      determined by isobolographic analysis or by analysis of the log dose-response
      curves for drug combination and drugs alone. Levetiracetam (10-200 mg/kg),
      ibuprofen (12.5-100 mg/kg), celecoxib (3.75-30 mg/kg), paracetamol (50-200
      mg/kg), caffeine (15-100 mg/kg), and 2-drug combinations of levetiracetam with
      analgesics/caffeine produced a significant, dose-dependent reduction of
      inflammatory hyperalgesia. Isobolographic analysis revealed that levetiracetam
      exerts a synergistic interaction with analgesics, with approximately 7-, 9-, and
      11-fold reduction of doses of both drugs in combination of levetiracetam with
      paracetamol, celecoxib, and ibuprofen, respectively. Analysis of the log dose
      response curves for levetiracetam (1-50 mg/kg) in the presence of caffeine (10
      mg/kg) and levetiracetam applied alone also revealed a synergistic interaction.
      Levetiracetam's ED50 in the presence of caffeine was reduced approximately 11
      fold. PERSPECTIVE: The presented data suggest that 2-drug combinations of
      levetiracetam and nonsteroidal analgesics or caffeine could be useful in
      treatment of inflammatory pain. The efficacy and the adverse effects of those
      mixtures should be explored further in clinical settings.

PMID- 23954520
TI  - An explanatory study evaluating the muscle relaxant effects of intramuscular
      magnesium sulphate for dystonia in complex regional pain syndrome.
AB  - The treatment of dystonia related to complex regional pain syndrome (CRPS)
      remains unsatisfactory, raising the need of alternative targets for intervention.
      In dystonia, pathologic muscle changes may occur, which contributes to stiffness.
      Because magnesium sulphate may act as a muscle relaxant through its actions on
      the neuromuscular junction and muscle, we performed an explanatory study of the
      muscle relaxant effect and safety of intramuscular magnesium sulphate (IMMG) in
      CRPS patients with dystonia. In a double-blind randomized placebo-controlled
      crossover study, 30 patients were assigned to 3-week treatments of IMMG and
      placebo. Treatments were separated by a 1-week washout period. The daily dose of
      IMMG was 1,000 mg in week 1, 1,500 mg in week 2, and 2,000 mg in week 3. The
      primary outcome measure was the difference in change in Burke-Fahn-Marsden scores
      after 3 weeks of treatment between both interventions. Secondary outcomes
      involved severity of dystonia, myoclonus, tremor, and pain, and functional
      activity. Data of 22 patients available for the explanatory analysis revealed no
      significant differences between IMMG and placebo treatment in any of the
      outcomes. In conclusion, we found no indication of efficacy of IMMG in a daily
      dose of 2,000 mg as a muscle relaxant in CRPS-related dystonia. PERSPECTIVE: In
      this double-blind placebo-controlled crossover study there was no evidence found
      of a muscle relaxant effect of intramuscular magnesium sulphate in dystonia
      related to CRPS. Consequently, there is insufficient support for new studies
      evaluating the efficacy of other routes of MG administration in CRPS-related
      dystonia.

PMID- 23954521
TI  - Palladium-catalyzed multi-component synthesis of steroidal A- and D-ring fused
      5,6-disubstituted pyridines under microwave irradiation.
AB  - The preparation of steroidal A-, D-ring fused 5,6-disubstituted pyridines and
      nonsteroidal substituted pyridines is described form Pd(OAc)2 catalyzed multi
      component reaction of steroidal/nonsteroidal beta-halovinyl aldehyde, alkyne and
      benzylamine in solvent-free condition under microwave irradiation. 

PMID- 23954519
TI  - Motives for medical misuse of prescription opioids among adolescents.
AB  - This study examined the motives for medical misuse of prescription opioids among
      adolescents and assessed differences in motives by demographic characteristics,
      substance abuse, and diversion behaviors. A survey was conducted in 2011 to 2012
      and the sample consisted of 2,964 adolescents (51% female). Thirteen percent
      reported past-year medical use of prescription opioids. Among those prescribed
      opioids in the past year (n = 393), 17.9% reported medical misuse (eg, using too
      much, using to get high, or using to increase alcohol or other drug effects). The
      most prevalent motives for medical misuse were "to relieve pain" (84.2%) and "to
      get high" (35.1%). Multivariate analyses indicated that the motives differed by
      race, and that different motives were associated with different substance abuse
      and diversion behaviors. The odds of past-year substance abuse among medical
      misusers motivated by non-pain relief were more than 15 times greater than for
      nonusers (adjusted odds ratio = 15.2, 95% CI = 6.4-36.2, P < .001). No such
      differences existed between nonusers and appropriate medical users, or between
      nonusers and medical misusers motivated by pain relief only. These findings
      improve our understanding of opioid medication misuse among adolescents and
      indicate the need for enhanced education about appropriate medical use, pain
      management, and patient communication with prescribers. PERSPECTIVE: This article
      represents the first investigation to examine the motives associated with medical
      misuse of prescription opioids among adolescents. The results indicate that the
      majority of medical misuse is associated with pain relief. This information could
      be used to develop strategies to reduce opioid medication misuse among
      adolescents.

PMID- 23954522
TI  - Stereoselective synthesis of novel antiproliferative steroidal (E, E) dienamides
      through a cascade aldol/cyclization process.
AB  - The stereoselective and metal-free protocol involving a cascade aldol/cyclization
      process for the synthesis of steroidal (E, E) dienamides from steroidal alpha,
      alpha-dicyanoalkene was reported. This protocol efficiently achieved the
      construction of C=C bond and selective conversion of cyano group into carboxamide
      in one-pot procedure under mild condition. Further biological evaluation showed
      that some of these compounds had moderate to excellent cytotoxic activities
      against all the tested cancer cell lines and were more potent than well-known
      drug 5-fluorouracil. Particularly, compound 3c represented excellent inhibitory
      effect against MCF-7 (IC50=0.76 MUM), which was about 10-fold more potent than 5
      fluorouracil.

PMID- 23954524
TI  - Comparison of the actual amount of axial movement of 3 aspheric intraocular
      lenses using anterior segment optical coherence tomography.
AB  - PURPOSE: To compare the mean effective lens position (ELP) and actual amount of
      axial movement of 3 aspheric intraocular lenses (IOLs) using anterior segment
      optical coherence tomography (AS-OCT). SETTING: Department of Ophthalmology,
      Korea University College of Medicine, Seoul, South Korea. DESIGN: Retrospective
      comparative study. METHODS: Consecutive patients had phacoemulsification with
      aspheric IOL implantation. The ELP measurements by AS-OCT were taken 1 week and
      1, 3, and 6 months postoperatively. The ELPRMS was defined as the root mean
      square (RMS) of the change in ELP at each follow-up timepoint. RESULTS: An XL
      Stabi ZO 3-plate IOL was implanted in 30 eyes, an Acrysof IQ C-loop IOL in 22
      eyes, and an Akreos MI-60 4-plate IOL in 17 eyes. The 4-plate IOL showed
      significant changes in the mean ELP from 1 week to 1 month and from 3 to 6 months
      postoperatively (P=.005 and P=.028, respectively). The changes of the other 2
      IOLs were insignificant during the 3 postoperative visits. However, the mean
      ELPRMS of the C-loop IOL (0.06 mm +/- 0.31 [SD]) was smaller than that of the 3
      plate IOL (0.14 +/- 0.28 mm) and the 4-plate IOL (0.20 +/- 0.35 mm) (P=.014 and
      P=.023, respectively) during the 3 timepoints. CONCLUSION: An appropriate method
      based on the actual amount of axial IOL movement, such as the ELPRMS, is needed
      to assess the axial positional stability of IOLs. FINANCIAL DISCLOSURE: No author
      has a financial or proprietary interest in any material or method mentioned.

PMID- 23954523
TI  - Mass spectrometry quantification of PICALM and AP180 in human frontal cortex and
      neural retina.
AB  - Recent genome-wide association studies have suggested that endocytic factors,
      such as phosphatidylinositol-binding clathrin assembly protein (PICALM), may be
      implicated in the development of Alzheimer disease (AD). The cellular functions
      of PICALM are in line with this possibility: (i) PICALM is involved in regulation
      of amyloid-beta levels and (ii) PICALM is important for a presynaptic function,
      which is diminished in AD. To facilitate the analysis of PICALM, we developed a
      quantitative method to assess the expression level of PICALM in various
      biological samples. For this purpose, a stable isotope-labeled quantification
      concatamer (QconCAT) of PICALM was designed, expressed, purified, and
      characterized. The PICALM QconCAT was first used as an internal standard in a
      multiple reaction monitoring assay to measure PICALM concentrations in the human
      frontal cortex, a tissue strongly affected by AD. A second endocytic factor that
      is highly homologous to PICALM and also functions in clathrin-mediated
      endocytosis, clathrin coat assembly protein AP180, was quantified as well.
      Because age-related macular degeneration shares several clinical and pathological
      features with AD, the measurements were then extended to human normal neural
      retina. Overall, the developed method is suitable for PICALM and AP180
      quantitative analysis in various biological samples of interest. 

PMID- 23954525
TI  - Accommodation in phakic and pseudophakic eyes measured with subjective and
      objective methods.
AB  - PURPOSE: To measure accommodation subjectively and objectively and assess
      anterior segment changes during accommodation in phakic eyes and pseudophakic
      eyes. SETTING: Department of Ophthalmology, Medical Health and Science Centre,
      University of Debrecen, Debrecen, Hungary. DESIGN: Case series. METHODS:
      Subjective and objective accommodation measurements and pupillometry were
      performed in phakic and pseudophakic patients. Refraction and pupil diameter were
      recorded with different accommodation stimuli. Corneal higher-order aberrations
      (HOAs) and anterior chamber depths (ACDs) were detected with a rotating
      Scheimpflug camera. RESULTS: The mean age of the 44 patients in the phakic group
      was 36.34 years +/- 16.6 (SD) and of the 27 patients in the pseudophakic group,
      69.3 +/- 9.98 years. The mean subjective accommodation was 4.49 +/- 3.48 diopters
      (D) in phakic eyes and showed significant correlation with age, spherical
      aberration, changes in pupil diameter, and ACD. The mean subjective accommodation
      was 0.50 +/- 0.28 D in pseudophakic eyes. In phakic eyes, the mean objective
      accommodation was 0.46 +/- 1.02 D, 1.06 +/- 1.33 D, and 2.2 +/- 1.9 D with 2.0 D,
      3.0 D, and 5.0 D, respectively, of stimulus. In pseudophakic eyes, measurable
      objective accommodation was recorded. In phakic eyes, the correlations were
      significant between these values and age, changes in ACD, pupil size, and corneal
      spherical aberration. In pseudophakic eyes, the only correlation was with the
      spherical equivalent value. CONCLUSIONS: The magnitude of accommodation was
      greater with subjective measures than objective measures. In pseudophakic eyes,
      senile miosis and HOAs can be regarded as underlying factors in subjective
      accommodation; however, objective accommodation is not clinically significant.
      FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 23954526
TI  - Ready-to-use injectable calcium phosphate bone cement paste as drug carrier.
AB  - Current developments in calcium phosphate cement (CPC) technology concern the use
      of ready-to-use injectable cement pastes by dispersing the cement powder in a
      water-miscible solvent, such that, after injection into the physiological
      environment, setting of cements occurs by diffusion of water into the cement
      paste. It has also been demonstrated recently that the combination of a water
      immiscible carrier liquid combined with suitable surfactants facilitates a
      discontinuous liquid exchange in CPC, enabling the cement setting reaction to
      take place. This paper reports on the use of these novel cement paste
      formulations as a controlled release system of antibiotics (gentamicin,
      vancomycin). Cement pastes were applied either as a one-component material, in
      which the solid drugs were physically dispersed, or as a two-component system,
      where the drugs were dissolved in an aqueous phase that was homogeneously mixed
      with the cement paste using a static mixing device during injection. Drug release
      profiles of both antibiotics from pre-mixed one- and two-component cements were
      characterized by an initial burst release of ~7-28%, followed by a typical square
      root of time release kinetic for vancomycin. Gentamicin release rates also
      decreased during the first days of the release study, but after ~1 week, the
      release rates were more or less constant over a period of several weeks. This
      anomalous release kinetic was attributed to participation of the sulfate counter
      ion in the cement setting reaction altering the drug solubility. The drug-loaded
      cement pastes showed high antimicrobial potency against Staphylococcus aureus in
      an agar diffusion test regime, while other cement properties such as mechanical
      performance or phase composition after setting were only marginally affected.

PMID- 23954527
TI  - Montelukast prevents microparticle-induced inflammatory and functional
      alterations in human bronchial smooth muscle cells.
AB  - Microparticles (MPs) are membrane fragments that may play a role in the
      pathogenesis of chronic respiratory diseases. We aimed to investigate whether
      human monocytes/macrophage-derived MPs could induce a pro-inflammatory phenotype
      in human bronchial smooth muscle cells (BSMC) and the effect of montelukast in
      this setting. Experimental methods included isolation of human
      monocytes/macrophages and generation of monocyte-derived MPs, RT-PCR analysis of
      gene expression, immunoenzymatic determination of pro-inflammatory factor
      release, bioluminescent assay of intracellular cAMP levels and electromobility
      shift assay analysis of NF-kappaB nuclear translocation. Stimulation of human
      BSMC with monocyte-derived MPs induced a pro-inflammatory switch in human BSMC by
      inducing gene expression (COX-2 and IL-8), protein release in the supernatant
      (PGE2 and IL-8), and heterologous beta2-adrenoceptor desensitization. The latter
      effect was most likely related to autocrine PGE2 since pre-treatment with COX
      inhibitors restored the ability of salbutamol to induce cAMP synthesis in
      desensitized cells. Challenge with MPs induced nuclear translocation of NF-kappaB
      and selective NF-kappaB inhibition decreased MP-induced cytokine release in the
      supernatant. Montelukast treatment prevented IL-8 release and heterologous beta2
      adrenoceptor desensitization in human BSMC exposed to monocyte-derived MPs by
      blocking NF-kappaB nuclear translocation. These findings provide evidence on the
      role of human monocyte-derived MPs in the airway smooth muscle phenotype switch
      as a novel potential mechanism in the progression of chronic respiratory diseases
      and on the protective effects by montelukast in this setting. 

PMID- 23954528
TI  - Radiation therapy dosimetry system.
AB  - New therapeutic treatments generally aim to increase therapeutic efficacy while
      minimizing toxicity. Many aspects of radiation dosimetry have been studied and
      developed particularly in the field of external radiation. The success of
      radiotherapy relies on monitoring the dose of radiation to which the tumor and
      the adjacent tissues are exposed. Radiotherapy techniques have evolved through a
      rapid transition from conventional three-dimensional (3D) conformal radiation
      therapy to intensity-modulated radiation therapy (IMRT) treatments or
      radiosurgery and robotic radiation therapy. These advances push the frontiers in
      our effort to provide better patient care by improving the precision of the
      absorbed dose delivered. This paper presents state-of-the art radiation therapy
      dosimetry techniques as well as the value of integral dosimetry (INDOS), which
      shows promise in the fulfillment of radiation therapy dosimetry requirements. 

PMID- 23954529
TI  - Safe conception for human immunodeficiency virus-discordant couples: the
      preexposure prophylaxis for conception alternative.

PMID- 23954530
TI  - Vitamin D deficiency in gestational diabetes mellitus and the role of the
      placenta.
AB  - OBJECTIVE: The aim of this study was to evaluate the relationships between
      maternal vitamin D levels and gestational diabetes mellitus (GDM) and differences
      in the placental production of vitamin D receptor (VDR), CYP24A, and CYP27B1.
      STUDY DESIGN: Forty normal pregnant women and 20 women with GDM were included in
      this study. Serum levels of 25-hydroxyvitamin D (25[OH]D) were measured with
      enzyme-linked immunosorbent assay. The expression and production of VDR, CYP27B1,
      and CYP24A1 in the placenta were evaluated with real time-polymerase chain
      reaction and Western blot, respectively. RESULTS: We found that 27.5% of normal
      pregnant women and 85% of women with GDM had vitamin D deficiency, with serum
      25(OH)D levels <20 ng/mL. Serum levels of 25(OH)D were lower in women with GDM
      than normal pregnant women (P < .01). The production of CYP24A1 protein and
      messenger RNA expression was significantly higher in placental tissue from
      patients with GDM than in those from normal pregnancies; however, the production
      of CYP27B1 and VDR protein and messenger RNA expression were not different
      between 2 the groups. CONCLUSION: In this study, vitamin D deficiency was
      associated with GDM. Given that 25(OH)D is hydroxylated by CYP27B1 to the
      bioactive 1,25(OH)2D form, and CYP24A1 catabolizes both 25(OH)D and 1,25(OH)2D to
      the inactive metabolites, respectively, our data indicate that the elevated
      activity of CYP24A1 in the placenta may play a key role in the development of
      vitamin D deficiency in GDM.

PMID- 23954531
TI  - National trends in primary cesarean delivery, labor attempts, and labor success,
      1990-2010.
AB  - OBJECTIVE: The national primary cesarean delivery rate increased until 2004, but
      after 2004, this rate cannot be tracked using Vital Statistics data.
      Additionally, it is unknown whether changes in the primary cesarean delivery rate
      reflect changes in the rate of labor attempts, labor success, or both. Here,
      using hospital discharge data, we examined national trends in primary cesarean
      deliveries, labor attempts, and labor success among women without prior cesarean
      delivery between 1990 and 2010. STUDY DESIGN: This analysis of serial cross
      sectional data from the National Hospital Discharge Survey used Joinpoint
      regression to assess trends over time and logistic regression with marginal
      effects to identify rates of change over time and adjust for demographic and
      clinical factors. RESULTS: The primary cesarean delivery rate declined 0.2
      percentage points per year (95% confidence interval [CI], 0.1-0.3) between 1990
      and 1999, increased 1.0 percentage point per year (95% CI, 0.8-1.2) between 1999
      and 2004, and increased 0.3 percentage points (95% CI, 0.1-0.6) per year from
      2004 until 2010. Between 1998 and 2005, the rate of labor attempts declined 0.4
      percentage points (95% CI, 0.3-0.5) per year. No changes in the labor attempt
      rate occurred between 2005 and 2010. Labor success rates increased 0.2 percentage
      points (95% CI, 0.1-0.3) per year between 1990 and 1998 but then declined 0.5
      (95% CI, 0.5-0.8) percentage points per year from 1998 to 2010. Adjusted results
      were similar. CONCLUSION: The primary cesarean delivery rate continued to
      increase after 2004. Increases in the primary cesarean delivery rate after 2005
      were driven by declines in labor success rates.

PMID- 23954532
TI  - A tool for teaching the B-Lynch brace suture method: an inexpensive new simulator
      allows obstetricians to polish an essential technique.
AB  - The B-Lynch brace suture is invaluable in the surgical management of postpartum
      hemorrhage, particularly as a fertility-sparing alternative to hysterectomy. In
      this video, we show how to create a low-cost simulator to teach the B-Lynch brace
      suture technique, followed by the intraoperative application of the same
      technique. 

PMID- 23954533
TI  - Cost-effectiveness of transabdominal ultrasound for cervical length screening for
      preterm birth prevention.
AB  - OBJECTIVE: Transabdominal ultrasound (TAUS) cervical length (CL) screening has
      been proposed as an alternative to universal transvaginal screening to identify
      women at an increased risk of preterm birth. We sought to identify whether and
      under what circumstances TAUS would be cost-effective. STUDY DESIGN: This is a
      decision analytic model designed to compare an initial TAUS CL screening approach
      with universal transvaginal screening in a hypothetical cohort of women with a
      singleton pregnancy. Cost, probability, and utility estimates were derived from
      the existing literature. RESULTS: Under baseline assumptions, universal
      transvaginal was the dominant strategy. In comparison to TAUS, universal
      transvaginal CL screening reduced preterm birth by 0.03%, reduced costs by $1.2
      million and increased quality-adjusted life years by 70 per 100,000 women.
      Although robust to many changes in many estimates, the model was sensitive to the
      cost of a transvaginal ultrasound, the prevalence of a short cervix and the test
      characteristics (ie, sensitivity and specificity) of a TAUS screening examination
      for short CL. CONCLUSION: Compared with an initial TAUS screen, universal
      transvaginal ultrasound was a more cost-effective strategy under most
      assumptions. Optimizing TAUS testing characteristics or applying a transabdominal
      screening strategy in lower risk populations may yield an initial TAUS to be cost
      effective.

PMID- 23954535
TI  - Microlaparoscopic bilateral adnexectomy: a 3-mm umbilical port and a pair of 2-mm
      ancillary trocars served as conduits.
AB  - We performed a microlaparoscopic bilateral salpingo-oophorectomy using a 3-mm
      umbilical port for bipolar instruments insertion and two 2-mm ports for the scope
      and the grasper. The transvaginal route was used for specimen retrieval. 

PMID- 23954534
TI  - Expectant management of severe preeclampsia remote from term: the MEXPRE Latin
      Study, a randomized, multicenter clinical trial.
AB  - OBJECTIVE: The objective of the study was to determine whether expectant
      management of severe preeclampsia prior to 34 weeks of gestation results in
      improved neonatal outcome in countries with limited resources. STUDY DESIGN: This
      was a randomized clinical trial performed in 8 tertiary hospitals in Latin
      America. Criteria of randomization included gestational age between 28 and 33
      weeks' gestation and the presence of severe hypertensive disorders. Patients were
      randomized to steroids with prompt delivery (PD group) after 48 hours vs steroids
      and expectant management (EXM group). The primary outcome was perinatal
      mortality. RESULTS: A total of 267 patients were randomized, 133 to the PD group
      and 134 to the EXM group. Pregnancy prolongation was 2.2 days for the PD group vs
      10.3 days for the EXM group (P = .0001). The rate of perinatal mortality (9.4% vs
      8.7%; P = .81; relative risk [RR], 0.91; 95% confidence interval [CI], 0.34-1.93)
      was not improved with expectant management, and neither was the composite of
      neonatal morbidities (56.4% vs 55.6%; P = .89; RR, 01.01; 95% CI, 0.81-1.26).
      There was no significant difference in maternal morbidity in the EXM group
      compared with the PD group (25.2% vs 20.3%; P = .34; RR, 1.24; 95% CI, 0.79
      1.94). However, small gestational age (21.7% vs 9.4%; P = .005; RR, 2.27; 95% CI,
      1.21-4.14) and abruption were more common with expectant management (RR, 5.07;
      95% CI, 1.13-22.7; P = .01). There were no maternal deaths. CONCLUSION: This
      study does not demonstrate neonatal benefit with expectant management of severe
      preeclampsia from 28 to 34 weeks. Additionally, a conservative approach may
      increase the risk of abruption and small for gestational age.

PMID- 23954536
TI  - What stands out in a scene? A study of human explicit saliency judgment.
AB  - Eye tracking has become the de facto standard measure of visual attention in
      tasks that range from free viewing to complex daily activities. In particular,
      saliency models are often evaluated by their ability to predict human gaze
      patterns. However, fixations are not only influenced by bottom-up saliency
      (computed by the models), but also by many top-down factors. Thus, comparing
      bottom-up saliency maps to eye fixations is challenging and has required that one
      tries to minimize top-down influences, for example by focusing on early fixations
      on a stimulus. Here we propose two complementary procedures to evaluate visual
      saliency. We seek whether humans have explicit and conscious access to the
      saliency computations believed to contribute to guiding attention and eye
      movements. In the first experiment, 70 observers were asked to choose which
      object stands out the most based on its low-level features in 100 images each
      containing only two objects. Using several state-of-the-art bottom-up visual
      saliency models that measure local and global spatial image outliers, we show
      that maximum saliency inside the selected object is significantly higher than
      inside the non-selected object and the background. Thus spatial outliers are a
      predictor of human judgments. Performance of this predictor is boosted by
      including object size as an additional feature. In the second experiment,
      observers were asked to draw a polygon circumscribing the most salient object in
      cluttered scenes. For each of 120 images, we show that a map built from
      annotations of 70 observers explains eye fixations of another 20 observers freely
      viewing the images, significantly above chance (dataset by Bruce and Tsotsos
      (2009); shuffled AUC score 0.62+/-0.07, chance 0.50, t-test p<0.05). We conclude
      that fixations agree with saliency judgments, and classic bottom-up saliency
      models explain both. We further find that computational models specifically
      designed for fixation prediction slightly outperform models designed for salient
      object detection over both types of data (i.e., fixations and objects). 

PMID- 23954537
TI  - Influence of biological matrix and artificial electrospun scaffolds on
      proliferation, differentiation and trophic factor synthesis of rat embryonic stem
      cells.
AB  - Two-dimensional vs three-dimensional culture conditions, such as the presence of
      extracellular matrix components, could deeply influence the cell fate and
      properties. In this paper we investigated proliferation, differentiation,
      survival, apoptosis, growth and neurotrophic factor synthesis of rat embryonic
      stem cells (RESCs) cultured in 2D and 3D conditions generated using Cultrex(r)
      Basement Membrane Extract (BME) and in poly-(L-lactic acid) (PLLA) electrospun
      sub-micrometric fibres. It is demonstrated that, in the absence of other
      instructive stimuli, growth, differentiation and paracrine activity of RESCs are
      directly affected by the different microenvironment provided by the scaffold. In
      particular, RESCs grown on an electrospun PLLA scaffolds coated or not with BME
      have a higher proliferation rate, higher production of bioactive nerve growth
      factor (NGF) and vascular endothelial growth factor (VEGF) compared to standard
      2D conditions, lasting for at least 2 weeks. Due to the high mechanical
      flexibility of PLLA electrospun scaffolds, the PLLA/stem cell culture system
      offers an interesting potential for implantable neural repair devices.

PMID- 23954538
TI  - Surface-enhanced Raman scattering and density functional theory study of 1,4
      benzenedithiol and its silver complexes.
AB  - This paper experimentally and theoretically investigated Raman and surface
      enhanced Raman scattering (SERS) of 1,4-benzenedithiol (1,4-BDT). Density
      functional theory methods were used to study Raman scattering spectra of isolated
      1,4-BDT and 1,4-BDT-Agn (n=2,4,6) complexes with B3LYP/6
      311+g(d)(C,H,S)/Lanl2dz(Ag) basis set. A full assignment of the Raman spectrum of
      1,4-BDT has been made based on the DFT analysis. The calculated data showed good
      agreement with experimental observations. The adsorption sites, metal cluster
      size, and HOMO-LUMO energies are discussed to give insight in the SERS mechanisms
      for 1,4-BDT molecules. 

PMID- 23954539
TI  - Analysis of molecular structure, spectroscopic properties (FT-IR, micro-Raman and
      UV-vis) and quantum chemical calculations of free and ligand 2-thiopheneglyoxylic
      acid in metal halides (Cd, Co, Cu, Ni and Zn).
AB  - In this study, molecular geometries, experimental vibrational wavenumbers,
      electronic properties and quantum chemical calculations of 2-thiopheneglyoxylic
      acid molecule, (C6H4O3S), and its metal halides (Cd, Co, Cu, Ni and Zn) which are
      used as pharmacologic agents have been investigated experimentally by FT-IR,
      micro-Raman and UV-visible spectroscopies and elemental analysis. Meanwhile the
      vibrational calculations were verified by DFT/B3LYP method with 6-311++G(d,p) and
      LANL2DZ basis sets in the ground state, for free TPGA molecule and its metal
      halide complexes, respectively, for the first time. The calculated fundamental
      vibrational frequencies for the title compounds are in a good agreement with the
      experimental data. 

PMID- 23954540
TI  - Mechanism of cinnamic acid-induced trypsin inhibition: a multi-technique
      approach.
AB  - In order to investigate the association of the protease trypsin with cinnamic
      acid, the interaction was characterized by using fluorescence, UV-vis absorption
      spectroscopy, molecular modeling and an enzymatic inhibition assay. The binding
      process may be outlined as follows: cinnamic acid can interact with trypsin with
      one binding site to form cinnamic acid-trypsin complex, resulting in inhibition
      of trypsin activity; the spectroscopic data show that the interaction is a
      spontaneous process with the estimated enthalpy and entropy changes being -8.95
      kJ mol(-1) and 50.70 J mol(-1) K(-1), respectively. Noncovalent interactions make
      the main contribution to stabilize the trypsin-cinnamic acid complex; cinnamic
      acid can enter into the primary substrate-binding pocket and alter the
      environment around Trp and Tyr residues.

PMID- 23954541
TI  - Spectroscopic and quantum chemical study of an alkaloid aristolochic acid I.
AB  - Aristolochic acids (AAs) (Aristolochiaceae) are used in the traditional Chinese
      herb medicine. We have presented the geometry optimization, electrostatic
      potential surface, frontier orbital energy gap and vibrational wavenumbers of
      aristolochic acid I (AA I) using ab initio Hartree-Fock (HF) and density
      functional theory (DFT/B3LYP) method employing 6-311G(d,p) basis set. A complete
      vibrational assignment has been done on the basis of calculations on monomer and
      dimer of AA I. The UV-vis absorption spectrum has been recorded in ethanol
      solvent and compared with the calculated one in the gas phase as well as in
      solvent environment (integral-equation formalism polarizable continuum model; IEF
      PCM) using TD-DFT/6-31G basis set. A short outline of the NBO analysis segment
      with their structural meaning has been presented. The variation of thermodynamic
      properties with temperature was calculated theoretically and the thermal response
      of the compound has been recorded with the help of differential scanning
      calorimetry (DSC) in N2 environment. 

PMID- 23954542
TI  - Non-invasive identification of metal-oxalate complexes on polychrome artwork
      surfaces by reflection mid-infrared spectroscopy.
AB  - In this work a reflection mid-infrared spectroscopy study of twelve metal-oxalate
      complexes, of interest in art conservation science as alteration compounds, was
      performed. Spectra of the reference materials highlighted the presence of
      derivative-like and/or inverted features for the fundamental vibrational modes as
      result of the main contribution from the surface component of the reflected
      light. In order to provide insights in the interpretation of theses spectral
      distortions, reflection spectra were compared with conventional transmission
      ones. The Kramers-Kronig (KK) algorithm, employed to correct for the surface
      reflection distortions, worked properly only for the derivative-like bands.
      Therefore, to pay attention to the use of this algorithm when interpreting the
      reflection spectra is recommended. The outcome of this investigation was
      exploited to discriminate among different oxalates on thirteen polychrome
      artworks analyzed in situ by reflection mid-infrared spectroscopy. The
      visualization of the nus(CO) modes (1400-1200 cm(-1)) and low wavenumber bands
      (below 900 cm(-1)) in the raw reflection profiles allowed Ca, Cu and Zn oxalates
      to be identified. Further information about the speciation of different hydration
      forms of calcium oxalates were obtained by using the KK transform. The work
      proves reflection mid-infrared spectroscopy to be a reliable and sensitive
      spectro-analytical method for identifying and mapping different metal-oxalate
      alteration compounds on the surface of artworks, thus providing conservation
      scientists with a non-invasive tool to obtain information on the state of
      conservation and causes of alteration of artworks.

PMID- 23954543
TI  - Growth morphologies and optical properties of LTA single crystal.
AB  - Atomic force microscopy (AFM) has been used to study the growth morphologies of l
      threonine acetate (abbreviated as LTA) crystal. Spiral growth hillocks and
      typical step patterns are described and discussed. Nuclei with various shapes
      often distribute at the larger step terraces. Eventually, in order to investigate
      microscopic second order nonlinear optical properties of LTA crystals, the
      molecular dipole moment (MU), polarizability (alpha), and first
      hyperpolarizability (beta) were computed using a series of basis sets including
      polarized and diffuse functions at the framework of Hartree-Fock and density
      functional theory methods. The study is helpful to the further development of l
      threonine analogs with improved nonlinear optical properties. 

PMID- 23954544
TI  - Synthesis and characterization of bis[N'-(4-carboxybenzylidene)]-pyridine-2,6
      dicarbohydrazide: colorimetric and fluorometric modulation in presence of F-
      ions.
AB  - A novel organic compound bis[N'-(4-carboxybenzylidene)]-pyridine-2,6
      dicarbohydrazide (L) was synthesized and characterized using spectroscopic and X
      ray diffraction techniques. Tetrabutyl ammonium halides [(Bu)4N(+)X(-)] X = F,
      Cl, Br and I were allowed to react separately with a solution of L in DMSO (1 *
      10(-5)M). The solution of L turned to shining yellow colour in the presence of F(
      ) ion only. The binding properties have been studied using absorption, emission
      and (1)H NMR titrations. Theoretical studies on compound L and compound L+X(-) (X
      = F, Cl and Br) in DMSO medium were carried out using density functional theory
      (DFT) at the B3LYP/6-31 G(d,p)/6-31 G+(d,p) level. The theoretical calculations
      agreed to the experimental results.

PMID- 23954546
TI  - Fixed-final-time optimal control of nonlinear systems with terminal constraints.
AB  - A model-based reinforcement learning algorithm is developed in this paper for
      fixed-final-time optimal control of nonlinear systems with soft and hard terminal
      constraints. Convergence of the algorithm, for linear in the weights neural
      networks, is proved through a novel idea by showing that the training algorithm
      is a contraction mapping. Once trained, the developed neurocontroller is capable
      of solving this class of optimal control problems for different initial
      conditions, different final times, and different terminal constraint surfaces
      providing some mild conditions hold. Three examples are provided and the
      numerical results demonstrate the versatility and the potential of the developed
      technique.

PMID- 23954545
TI  - Investigation of the inclusion interaction of p-sulfonatocalix[6]arene with
      triamterene.
AB  - The inclusion complexation behavior of p-sulfonatocalix[6]arene (SCX6) with
      triamterene (TA) was investigated by fluorescence spectroscopy, UV-Vis
      spectroscopy, (1)H and 2D NMR, FT-IR, SEM and DSC. The results indicate that TA
      is able to form an inclusion complex with SCX6. The inclusion complex has a
      stoichiometry of 1:1 at pH 6.50. In addition, the water solubility of TA was
      obviously increased in the inclusion complex with SCX6. 

PMID- 23954547
TI  - Investigation of the functional role of aldose 1-epimerase in engineered
      cellobiose utilization.
AB  - Functional expression of a cellodextrin transporter and an intracellular beta
      glucosidase from Neurospora crassa in Saccharomyces cerevisiae enables
      simultaneous co-fermentation of cellobiose and non-glucose sugars such as xylose.
      Here we investigate the functional role of aldose 1-epimerase (AEP) in engineered
      cellobiose utilization. One AEP (Gal10) and two putative AEPs (Yhr210c and
      Ynr071c sharing 50.6% and 51.0% amino acid identity with Gal10, respectively)
      were selected. Deletion of GAL10 led to complete loss of both AEP activity and
      cell growth on cellobiose, while GAL10 complementation restored the AEP activity
      and cell growth. In addition, deletion of YHR210C or YNR071C resulted in improved
      cellobiose utilization. These results suggest that the intracellular mutarotation
      of beta-glucose to alpha-glucose might be a rate controlling step and Gal10 play
      a crucial role in cellobiose fermentation by engineered S. cerevisiae. 

PMID- 23954548
TI  - Limiting similarity, species packing, and the shape of competition kernels.
AB  - A traditional question in community ecology is whether species' traits are
      distributed as more-or-less regularly spaced clusters. Interspecific competition
      has been suggested to play a role in such structuring of communities. The seminal
      theoretical work on limiting similarity and species packing, presented four
      decades ago by Robert MacArthur, Richard Levins and Robert May, has recently been
      extended. There is now a deeper understanding of how competitive interactions
      influence community structure, for instance, how the shape of competition kernels
      can determine the clustering of species' traits. Competition is typically weaker
      for greater phenotypic difference, and the shape of the dependence defines a
      competition kernel. The clustering tendencies of kernels interact with other
      effects, such as variation in resource availability along a niche axis, but the
      kernel shape can have a decisive influence on community structure. Here we review
      and further extend the recent developments and evaluate their importance. 

PMID- 23954549
TI  - Results from a post-launch monitoring survey on consumer purchases of foods with
      added phytosterols in five European countries.
AB  - Phytosterols (plant sterols and stanols), in the form of phytosterol-esters, are
      used in food products as active ingredients to lower elevated blood low density
      lipoprotein-cholesterol concentrations. In Europe, plant sterol-esters gained
      Novel Foods authorisation in 2000. As a requirement of the authorisation,
      Unilever developed a post-launch monitoring program to monitor the use of
      products with added phytosterols. This paper reports findings from the 2011 post
      launch monitoring survey on consumer purchase behaviour of foods with added
      phytosterols. 91,000 households in the Netherlands, Belgium, United Kingdom,
      France and Germany were included. 11,612 purchased foods with added phytosterols,
      including spreads, salad dressings, milk- and yoghurt-type products. The results
      show that 71-82% of households purchasing products with added phytosterols were 1
      2 person households. These households were also purchasing the majority of the
      volume sold in each country (75-85%). The average phytosterol intakes per
      household were 0.35-0.86 g/day; well below the 1.5-3.0 g/day phytosterols needed
      to achieve a significant blood cholesterol lowering benefit. Post-launch
      monitoring is an accepted and useful tool to estimate the consumption behaviour
      amongst different consumer groups. Data show that average phytosterol intakes per
      household were well below 1g/day, suggesting that overconsumption is unlikely.

PMID- 23954550
TI  - Environmental level of cadmium exposure stimulates osteoclasts formation in male
      rats.
AB  - Low level of cadmium (Cd) exposure may enhance osteoclasts formation in vitro.
      The aim of the study was to observe the effects of Cd on osteoclasts formation in
      vivo. Sprague-Dawley male rats were divided into 4 groups which were given Cd via
      drinking water at concentrations of 0, 2, 10 and 50 mg/L for 12 weeks. At the
      12th week, urine samples were collected from all of the rats. All rats were then
      sacrificed and the blood was collected for biomarkers assay. Bone tissues were
      dissected for mineral density determinations, histological investigation,
      tartrate resistant acid phosphatase staining and immunohistochemical staining.
      The bone mineral density and bone microstructure index of rats treated with 50mg
      Cd/L were obviously lower than in control rats. Histochemical investigation
      showed that Cd could induce osteoclasts formation in a dose-dependent manner.
      Tartrate resistant acid phosphatase 5b levels in rats treated with Cd were higher
      than the control. Immunohistochemical investigation showed that Cd could enhance
      receptor-activated nuclear factor kappa B ligand expression (RANKL) and inhibit
      osteoprotegerin (OPG) expression. Our study evidences in vivo that excessive bone
      resorption mediated via osteoclasts is an important way for Cd toxic effects on
      bone and OPG/RANKL may play an important role.

PMID- 23954551
TI  - Evaluation of the utility of the lifetime mouse bioassay in the identification of
      cancer hazards for humans.
AB  - Limited testing resources, the need to limit animal use, and the demand for
      better knowledge about carcinogenic hazards require that the carcinogenicity
      testing paradigm based on lifetime cancer bioassays in rats and mice should be as
      efficient and reliable as possible. We have therefore reevaluated the rodent
      bioassay, particularly for nongenotoxic chemicals and conducted a rigorous
      examination of the 710 substances listed in the Carcinogenic Potency Database
      (CPDB) that were tested in both mice and rats. The CPDB is a web-based database
      that provides access to the literature and the results of 6540 bioassays on 1547
      chemicals that have been published in the general literature through 2001 and by
      the National Cancer Institute/National Toxicology Program through 2004. Only
      three chemicals (o-benzyl-p-chlorophenol, Elmiron(r), p-tolylurea) were
      identified as unequivocally non-genotoxic, mouse non-liver carcinogens. A careful
      analysis showed that their carcinogenicity in mice is irrelevant for assessment
      of human cancer hazards. This is consistent with data showing, with a few well
      known exceptions, that non-genotoxic carcinogens in rodents are considered to be
      non-carcinogenic to humans. As a result, we propose that the inclusion of the
      mouse bioassay in the standard assessment scheme for non-genotoxic chemicals is
      no longer necessary. 

PMID- 23954552
TI  - Acrylamide exposure among Turkish toddlers from selected cereal-based baby food
      samples.
AB  - In this study, acrylamide exposure from selected cereal-based baby food samples
      was investigated among toddlers aged 1-3 years in Turkey. The study contained
      three steps. The first step was collecting food consumption data and toddlers'
      physical properties, such as gender, age and body weight, using a questionnaire
      given to parents by a trained interviewer between January and March 2012. The
      second step was determining the acrylamide levels in food samples that were
      reported on by the parents in the questionnaire, using a gas chromatography-mass
      spectrometry (GC-MS) method. The last step was combining the determined
      acrylamide levels in selected food samples with individual food consumption and
      body weight data using a deterministic approach to estimate the acrylamide
      exposure levels. The mean acrylamide levels of baby biscuits, breads, baby bread
      rusks, crackers, biscuits, breakfast cereals and powdered cereal-based baby foods
      were 153, 225, 121, 604, 495, 290 and 36 MUg/kg, respectively. The minimum, mean
      and maximum acrylamide exposures were estimated to be 0.06, 1.43 and 6.41 MUg/kg
      BW per day, respectively. The foods that contributed to acrylamide exposure were
      aligned from high to low as bread, crackers, biscuits, baby biscuits, powdered
      cereal-based baby foods, baby bread-rusks and breakfast cereals.

PMID- 23954553
TI  - The role of sphingolipid metabolism in cutaneous permeability barrier formation.
AB  - The epidermal permeability barrier of mammalian skin is localized in the stratum
      corneum. Corneocytes are embedded in an extracellular, highly ordered lipid
      matrix of hydrophobic lipids consisting of about 50% ceramides, 25% cholesterol
      and 15% long and very long chain fatty acids. The most important lipids for the
      epidermal barrier are ceramides. The scaffold of the lipid matrix is built of
      acylceramides, containing omega-hydroxylated very long chain fatty acids,
      acylated at the omega-position with linoleic acid. After glucosylation of the
      acylceramides at Golgi membranes and secretion, the linoleic acid residues are
      replaced by glutamate residues originating from proteins exposed on the surface
      of corneocytes. Removal of their glucosyl residues generates a hydrophobic
      surface on the corneocytes used as a template for the formation of extracellular
      lipid layers of the water permeability barrier. Misregulation or defects in the
      formation of extracellular ceramide structures disturb barrier function.
      Important anabolic steps are the synthesis of ultra long chain fatty acids, their
      omega-hydroxylation, and formation of ultra long chain ceramides and
      glucosylceramides. The main probarrier precursor lipids, glucosylceramides and
      sphingomyelins, are packed in lamellar bodies together with hydrolytic enzymes
      such as glucosylceramide-beta-glucosidase and acid sphingomyelinase and secreted
      into the intercelullar space between the stratum corneum and stratum granulosum.
      Inherited defects in the extracellular hydrolytic processing of the probarrier
      acylglucosylceramides impair epidermal barrier formation and cause fatal
      diseases: such as prosaposin deficiency resulting in lack of lysosomal lipid
      binding and transfer proteins, or the symptomatic clinical picture of the
      "collodion baby" in the absence of glucocerebrosidase. This article is part of a
      Special Issue entitled The Important Role of Lipids in the Epidermis and their
      Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors:
      Kenneth R. Feingold and Peter Elias.

PMID- 23954554
TI  - The roles of ABCA12 in epidermal lipid barrier formation and keratinocyte
      differentiation.
AB  - ATP-binding cassette (ABC) transporters form a large superfamily of transporters
      that bind and hydrolyze ATP to transport various molecules across limiting
      membranes or into vesicles. The ABCA subfamily members are thought to transport
      lipid materials. ABCA12 is a keratinocyte transmembrane lipid transporter protein
      associated with the transport of lipids via lamellar granules. ABCA12 is
      considered to transport lipids including ceramides to form extracellular lipid
      layers in the stratum corneum of the epidermis, which is essential for skin
      barrier function. ABCA12 mutations are known to underlie the three major types of
      autosomal recessive congenital ichthyoses: harlequin ichthyosis, lamellar
      ichthyosis and congenital ichthyosiform erythroderma. ABCA12 mutations result in
      defective lipid transport via lamellar granules in the keratinocytes, leading to
      ichthyosis phenotypes from malformation of the stratum corneum lipid barrier.
      Studies on ABCA12-deficient bioengineered models have revealed that lipid
      transport by ABCA12 is required for keratinocyte differentiation and epidermal
      morphogenesis. Defective lipid transport due to loss of ABCA12 function leads to
      the accumulation of intracellular lipids, including glucosylceramides and
      gangliosides, in the epidermal keratinocytes. The accumulation of gangliosides
      seems to result in the apoptosis of Abca12(-/-) keratinocytes. It was reported
      that AKT activation occurs in Abca12(-/-) granular-layer keratinocytes, which
      suggests that AKT activation serves to prevent the cell death of Abca12(-/-)
      keratinocytes. This article is part of a Special Issue entitled The Important
      Role of Lipids in the Epidermis and their Role in the Formation and Maintenance
      of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. 

PMID- 23954555
TI  - The role of lipoxygenases in epidermis.
AB  - Lipoxygenases (LOX) are key enzymes in the biosynthesis of a variety of highly
      active oxylipins which act as signaling molecules involved in the regulation of
      many biological processes. LOX are also able to oxidize complex lipids and modify
      membrane structures leading to structural changes that play a role in the
      maturation and terminal differentiation of various cell types. The mammalian skin
      represents a tissue with highly abundant and diverse LOX metabolism. Individual
      LOX isozymes are thought to play a role in the modulation of epithelial
      proliferation and/or differentiation as well as in inflammation, wound healing,
      inflammatory skin diseases and cancer. Emerging evidence indicates a structural
      function of a particular LOX pathway in the maintenance of skin permeability
      barrier. Loss-of-function mutations in the LOX genes ALOX12B and ALOXE3 have been
      found to represent the second most common cause of autosomal recessive congenital
      ichthyosis and targeted disruption of the corresponding LOX genes in mice
      resulted in neonatal death due to a severely impaired permeability barrier
      function. Recent data indicate that LOX action in barrier function can be traced
      back to the oxygenation of linoleate-containing ceramides which constitutes an
      important step in the formation of the corneocyte lipid envelope. This article is
      part of a Special Issue entitled The Important Role of Lipids in the Epidermis
      and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest
      Editors: Kenneth R. Feingold and Peter Elias. 

PMID- 23954557
TI  - Electromyographic activity of rectus capitis posterior minor muscles associated
      with voluntary retraction of the head.
AB  - BACKGROUND CONTEXT: The functional role of rectus capitis posterior minor (RCPm)
      muscles is not well defined. To the best of our knowledge, electromyographic
      (EMG) data from RCPm muscles in humans have never been collected and analyzed.
      PURPOSE: To test the null hypothesis that there will be no difference in
      normalized levels of EMG activity measured from RCPm muscles with the head in a
      neutral position and with the head in a retracted position. STUDY DESIGN: A
      repeated measures design intended to quantify normalized levels of EMG activity
      measured from RCPm muscles. METHODS: Disposable 25-gauge, bipolar fine wire
      hooked electrodes were used to collect EMG data from both right and left RCPm
      muscles from 17 asymptomatic subjects. Data were collected while subjects
      performed five trials with the head maintained in a neutral position; performed
      three maximal voluntary isometric contraction efforts; performed four trials with
      the head maintained in a retracted position. Mixed effects beta regression models
      were used to analyze the data. RESULTS: Normalized EMG activity of RCPm muscles
      collected with the subject's head held in a retracted position was significantly
      higher (p<.0001) than normalized EMG activity collected with the subject's head
      held in a self-selected, neutral position. CONCLUSIONS: Rectus capitis posterior
      minor muscles are active when the head is held in a neutral position and show a
      significant increase in activity when the head is held in a retracted position.

PMID- 23954558
TI  - Intraoperative assessment of human spinal cord perfusion using near infrared
      spectroscopy with indocyanine green tracer technique.
AB  - BACKGROUND CONTEXT: Despite the significant interest in the assessment of human
      cerebral perfusion, investigations into human spinal cord perfusion (SCP) are
      scarce. Current intraoperative monitoring of spinal cord relies on the assessment
      of neural conduction as a surrogate for SCP. However, there are various inherent
      limitations associated with the use of these techniques. Near infrared
      spectroscopy (NIRS) has been successfully used for monitoring and assessment of
      human cerebral perfusion and has shown promising results in intraoperative
      assessment of SCP in animal models. PURPOSE: The aim of this study was to
      investigate whether it is possible to monitor physiological changes in human SCP
      intraoperatively using NIRS with indocyanine green (ICG) tracer technique. We
      used this technique to calculate the human spinal cord carbon dioxide (CO2)
      reactivity index. In addition, we investigated whether the lamina causes
      significant attenuation of NIRS signals. STUDY DESIGN/SETTING: Intraoperative
      human experimental study. PATIENT SAMPLE: Eighteen patients undergoing elective
      posterior cervical spine surgery. OUTCOME MEASURES: Carbon dioxide reactivity of
      human SCP. METHODS: Nine patients underwent transdural assessment of SCP, with an
      additional nine patients undergoing translaminar measurements. Patients' SCP was
      continuously monitored using an NIRO-500 NIRS monitor via a set of purpose built
      optodes. Their arterial ICG concentration was simultaneously assessed using a
      pulse dye densitometer. Patients' end-tidal CO2 was gradually increased by 7.5 mm
      Hg and then returned back to baseline. Three sets of measurements were taken:
      baseline, hypercapnic, and return to baseline. RESULTS: After hypercapnia, SCP
      increased by a mean of 57.2 +/- 23.3% in the transdural group and 46.6 +/- 36.3%
      in the translaminar group. Carbon dioxide reactivity index was 7.6 +/-
      3.2%DeltaSCP/mm Hg in the transdural group and 6.4 +/- 5.3 %DeltaSCP/mm Hg in the
      translaminar group. There was no significant difference in the increase in SCP
      (p=.475) or the CO2 reactivity index (p=.581) observed between the transdural and
      the translaminar groups. CONCLUSIONS: Intraoperative NIRS with ICG tracer
      technique can identify an increase in the SCP in response to hypercapnia. It is
      possible to use this technique for monitoring SCP over the dura and the lamina.
      This technique could potentially be used to provide insight in to the
      pathophysiology and autoregulation of commonly acquired spinal cord conditions.
      Further research assessing the use of NIRS for monitoring of SCP is required.

PMID- 23954556
TI  - Sphingolipids and lifespan regulation.
AB  - Diseases including cancer, type 2 diabetes, cardiovascular and immune dysfunction
      and neurodegeneration become more prevalent as we age, and combined with the
      increase in average human lifespan, place an ever increasing burden on the health
      care system. In this chapter we focus on finding ways of modulating sphingolipids
      to prevent the development of age-associated diseases or delay their onset, both
      of which could improve health in elderly, fragile people. Reducing the incidence
      of or delaying the onset of diseases of aging has blossomed in the past decade
      because of advances in understanding signal transduction pathways and cellular
      processes, especially in model organisms, that are largely conserved in most
      eukaryotes and that can be modulated to reduce signs of aging and increase health
      span. In model organisms such interventions must also increase lifespan to be
      considered significant, but this is not a requirement for use in humans. The most
      encouraging interventions in model organisms involve lowering the concentration
      of one or more sphingolipids so as to reduce the activity of key signaling
      pathways, one of the most promising being the Target of Rapamycin Complex 1
      (TORC1) protein kinase pathway. Other potential ways in which modulating
      sphingolipids may contribute to improving the health profile of the elderly is by
      reducing oxidative stresses, inflammatory responses and growth factor signaling.
      Lastly, perhaps the most interesting way to modulate sphingolipids and promote
      longevity is by lowering the activity of serine palmitoyltransferase, the first
      enzyme in the de novo sphingolipid biosynthesis pathway. Available data in yeasts
      and rodents are encouraging and as we gain insights into molecular mechanisms the
      strategies for improving human health by modulating sphingolipids will become
      more apparent. This article is part of a Special Issue entitled New Frontiers in
      Sphingolipid Biology. 

PMID- 23954559
TI  - Comparison of the osteogenic potential of bone dust and iliac bone chip.
AB  - BACKGROUND CONTEXT: There is no comparative study of the in vitro and in vivo
      osteogenic potential of iliac bone chips (autogenous iliac cancellous bone chips)
      compared with bone dusts generated during the decortication process with a high
      speed burr in spine fracture or fusion surgery. PURPOSE: To compare the
      osteogenic potential of three sizes of bone dusts with iliac bone chips and to
      determine whether bone dusts can be used as a bone graft substitute. STUDY
      DESIGN: In vitro and in vivo study. METHODS: Bone chips were harvested from the
      posterior superior iliac spine and bone dusts from the vertebrae of 15 patients
      who underwent spinal fracture surgery. Bone dust was divided into three groups:
      small (3 mm), middle (4 mm), and large (5 mm) according to the size of the burr
      tip. A comparison was made using a cell proliferation assay, alkaline phosphatase
      (ALP) activity, the degree of mineralization in an in vitro model, and
      radiographic and histologic studies (the change of absorbable area and tissue
      density) after implantation of the various materials into back muscles of nude
      mice. RESULTS: Although all three bone dust groups were less active with regard
      to cell proliferation, ALP activity, and the degree of mineralization, than were
      bone chips, they still exhibited osteogenic potential. Furthermore, there was no
      significant difference among the three bone dust groups. The three bone dust
      groups did show greater absorbable area and change of the tissue density than did
      the iliac bone chip group. Again, there was no significant difference among the
      three bone dust groups in this regard. Histologically, specimens from the bone
      dust groups had a higher osteoclast cell number than specimens from the iliac
      bone chip group. CONCLUSIONS: The osteogenic potential of bone dusts is lower
      than that of iliac bone chips, and the absorption speed of bone dusts in vivo is
      faster than that of iliac bone chips. The increased resorption speed appeared to
      result from an increase in osteoclast cell number. Therefore, caution needs to be
      used when surgeons employ bone dust as a bone graft substitute.

PMID- 23954560
TI  - Home-based treadmill training to improve gait performance in persons with a
      chronic transfemoral amputation.
AB  - OBJECTIVE: To investigate the effectiveness of a home-based multiple-speed
      treadmill training program to improve gait performance in persons with a
      transfemoral amputation (TFA). DESIGN: Repeated measures. SETTING: Research
      laboratory. PARTICIPANTS: Individuals with a TFA (N=8) who had undergone a
      unilateral amputation at least 3 years prior as a result of limb trauma or
      cancer. INTERVENTION: Home-based treadmill walking for a total of 30 minutes a
      day, 3 days per week for 8 weeks. Each 30-minute training session involved 5
      cycles of walking for 2 minutes at 3 speeds. MAIN OUTCOME MEASURES: Participants
      were tested pretraining and after 4 and 8 weeks of training. The primary measures
      were temporal-spatial gait performance (symmetry ratios for stance phase duration
      and step length), physiological gait performance (energy expenditure and energy
      cost), and functional gait performance (self-selected walking speed [SSWS],
      maximum walking speed [MWS], and 2-minute walk test [2MWT]). RESULTS: Eight weeks
      of home-based training improved temporal-spatial gait symmetry at SSWS but not at
      MWS. A relative interlimb increase in stance duration for the prosthetic limb and
      proportionally greater increases in step length for the limb taking shorter steps
      produced the improved symmetry. The training effect was significant for the step
      length symmetry ratio within the first 4 weeks of the program. Energy expenditure
      decreased progressively during the training with nearly 10% improvement observed
      across the range of walking speeds. SSWS, MWS, and 2MWT all increased by 16% to
      20%. CONCLUSIONS: Home-based treadmill walking is an effective method to improve
      gait performance in persons with TFA. The results support the application of
      training interventions beyond the initial rehabilitation phase, even in
      individuals considered highly functional.

PMID- 23954562
TI  - The relationship between parental alcohol use and college students' alcohol
      related cognitions.
AB  - This study examined how parental and cognitive factors are structurally related
      to college students' intention to drink alcohol as well as possible gender
      differences in these relationships. Multiple-group comparison was used in
      structural equation modeling to assess data-to-model fit of the hypothesized
      model. Perceived parental alcohol use, positive expectancies, abstinence self
      efficacy in social situations, and intent to drink alcohol were structurally
      modeled and examined in 714 college students based on self-report measures.
      Results showed good fit of the hypothesized model in both men and women.
      Invariance of model fit was found across genders, although a more detailed
      analysis of the results suggested gender-specific influence of parental alcohol
      use over students' cognitions. Perceptions of greater parental alcohol use were
      associated with higher positive expectancies for alcohol use, which, in turn,
      were significantly related to lower drink refusal self-efficacy. Both higher
      expectancies and lower refusal self-efficacy were related to the intention for
      future use. Results of the study shed light on the development of alcohol-related
      cognitions in male and female college students and contribute to our
      understanding of the structural relationship between expectancies and self
      efficacy in alcohol use. 

PMID- 23954561
TI  - Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated
      macrophage innate immune function disruption.
AB  - Arsenic exposure is known to disrupt innate immune functions in humans and in
      experimental animals. In this study, we provide a mechanism by which arsenic
      trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage
      cells diminished internalization of FITC-labeled latex beads, impaired clearance
      of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory
      cytokines. These impairments in macrophage functions are associated with ATO
      induced unfolded protein response (UPR) signaling pathway characterized by the
      enhancement in proteins such as GRP78, p-PERK, p-eIF2alpha, ATF4 and CHOP. The
      expression of these proteins is altered both at transcriptional and translational
      levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA)
      attenuated the ATO-induced activation in UPR signaling and afforded protection
      against ATO-induced disruption of macrophage functions. This treatment also
      reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly,
      treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only
      reduced ROS production and UPR signaling but also improved macrophage functions.
      These data demonstrate that UPR signaling and ROS generation are interdependent
      and are involved in the arsenic-induced pathobiology of macrophage. These data
      also provide a novel strategy to block the ATO-dependent impairment in innate
      immune responses. 

PMID- 23954563
TI  - Adolescents' nonmedical use and excessive medical use of prescription medications
      and the identification of substance use subgroups.
AB  - The purpose of this study was to identify subgroups of adolescents based on their
      past 12 months use of tobacco, alcohol, marijuana, illicit drugs, and nonmedical
      use and excessive medical use of prescription medications. A cross-sectional Web
      based survey of adolescents from two middle and high school districts in
      Southeastern Michigan was conducted. The sample included 2,744 middle school (7th
      and 8th grade) and high school (9th through 12th grade) students. Participants
      had a mean age of 14.8 years (SD = 1.9 years); 50.4% were female, 64.1% were
      Caucasian, and 30.6% were African American. Participants completed measures of
      the past 12 months of substance use, parental monitoring, parental substance use,
      and internalizing and externalizing problems. Exploratory latent class analysis
      (LCA) indicated four classes. The largest class was composed of participants with
      low probabilities of using any substances (low/no use class), and the smallest
      class was composed of participants with relatively high probabilities of using
      all substances (multiple substances class). A third class included participants
      with high probabilities of using tobacco, alcohol, and marijuana (TAM). The
      fourth class consisted of participants with relatively high probabilities of
      alcohol use, nonmedical prescription drug use, and excessive medical use of
      prescription drugs (ANM). Female gender predicted membership in the ANM and
      multiple substance classes, and parental monitoring, parental substance use
      problems, internalizing, and externalizing problems uniquely predicted membership
      in all three high-risk risk classes. Results indicated three high-risk subgroups
      of adolescents, each characterized by a different pattern of substance use. Two
      risk groups are characterized by relatively high probabilities of nonmedical use
      and excessive medical use of prescription medications.

PMID- 23954564
TI  - The role of behavioral inhibition and behavioral approach systems in the
      associations between mood and alcohol consequences in college: a longitudinal
      multilevel analysis.
AB  - The behavioral inhibition system (BIS) and behavioral approach system (BAS) are
      thought to influence sensitivity to reinforcement and punishment, making them
      useful for predicting mood-related drinking outcomes. This study provided the
      first examination of BIS and BAS as moderators of longitudinal within-person
      associations between mood and alcohol-related consequences in college student
      drinkers. Participants (N = 637) at two public U.S. universities completed up to
      14 online surveys over the first three years of college assessing past-month
      general positive and negative moods, as well as past-month alcohol use and
      consequences. BIS and BAS were assessed at baseline. Using multilevel regression,
      we found that BIS and BAS moderated the within-person associations between
      negative mood and alcohol consequences. For students high on BIS only, high on
      BAS only, or high on both BIS and BAS, within-person increases in negative mood
      were associated with greater alcohol consequences in the first year of college.
      However, these negative mood-alcohol consequence associations diminished over
      time for students high on BIS and low on BAS, but remained strong for students
      high on both BIS and BAS. Within-person associations between positive mood and
      alcohol consequences changed from slightly positive to slightly negative over
      time, but were not moderated by BIS or BAS. Findings suggest that BIS and BAS
      impact the within-person association between general changes in negative mood and
      negative alcohol consequences, working jointly to maintain this relationship over
      time.

PMID- 23954565
TI  - Methods to detect replication-dependent and replication-independent DNA structure
      induced genetic instability.
AB  - DNA can adopt a variety of alternative secondary (i.e., non-B DNA) conformations
      that play important roles in cellular metabolism, including genetic instability,
      disease etiology and evolution. While we still have much to learn, research in
      this field has expanded dramatically in the past decade. We have summarized in
      our previous Methods review (Wang et al., Methods, 2009) some commonly used
      techniques to determine non-B DNA structural conformations and non-B DNA-induced
      genetic instability in prokaryotes and eukaryotes. Since that time, we and others
      have further characterized mechanisms involved in DNA structure-induced
      mutagenesis and have proposed both replication-dependent and replication
      independent models. Thus, in this review, we highlight some current methodologies
      to identify DNA replication-related and replication-independent mutations
      occurring at non-B DNA regions to allow for a better understanding of the
      mechanisms underlying DNA structure-induced genetic instability. We also describe
      a new web-based search engine to identify potential intramolecular triplex (H
      DNA) and left-handed Z-DNA-forming motifs in entire genomes or at selected
      sequences of interest. 

PMID- 23954569
TI  - Comparative proteomic analysis of the contractile-protein-depleted fraction from
      normal versus dystrophic skeletal muscle.
AB  - In basic and applied myology, gel-based proteomics is routinely used for studying
      global changes in the protein constellation of contractile fibers during
      myogenesis, physiological adaptations, neuromuscular degeneration, and the
      natural aging process. Since the main proteins of the actomyosin apparatus and
      its auxiliary sarcomeric components often negate weak signals from minor muscle
      proteins during proteomic investigations, we have here evaluated whether a simple
      prefractionation step can be employed to eliminate certain aspects of this
      analytical obstacle. To remove a large portion of highly abundant contractile
      proteins from skeletal muscle homogenates without the usage of major manipulative
      steps, differential centrifugation was used to decisively reduce the sample
      complexity of crude muscle tissue extracts. The resulting protein fraction was
      separated by two-dimensional gel electrophoresis, and 2D-landmark proteins were
      identified by mass spectrometry. To evaluate the suitability of the contractile
      protein-depleted fraction for comparative proteomics, normal versus dystrophic
      muscle preparations were examined. The mass spectrometric analysis of
      differentially expressed proteins, as determined by fluorescence difference in
      gel electrophoresis, identified 10 protein species in dystrophic mdx hindlimb
      muscles. Interesting new biomarker candidates included Hsp70, transferrin, and
      ferritin, whereby their altered concentration levels in dystrophin-deficient
      muscle were confirmed by immunoblotting. 

PMID- 23954570
TI  - Monitoring of DNA-protein interaction with single gold nanoparticles by localized
      scattering plasmon resonance spectroscopy.
AB  - We reported a sensitive detection system for measuring DNA-protein interaction at
      single plasmonic metal nanoparticles level by Localized Scattering Plasmon
      Resonance (LSPR) spectroscopy. As a proof of concept, DNA molecules were
      conjugated to gold nanoparticles (AuNPs) through gold-thiol chemistry and the
      resulted complex was served as single-particle probes of human topoisomerase I
      (TOPO). By recording the changes in Rayleigh light scattering signal of the
      individual nanoparticles upon protein binding, DNA-protein interaction was
      monitored and measured. The lambdamax shifts in LSPR spectrum of individual AuNP
      was found to be highly correlated with the amount of TOPO that bound onto. This
      technique provides a sensitive and high-throughput platform to screen and monitor
      accurately the specific biomolecular interactions. It is capable of revealing
      information such as particle-particle variations that might be buried in
      conventional bulk measurement. 

PMID- 23954568
TI  - Sex differences in the association of urinary bisphenol-A concentration with
      selected indices of glucose homeostasis among U.S. adults.
AB  - PURPOSE: Emerging evidence suggests that exposure to endocrine disruptors may
      initiate or exacerbate adiposity and associated health problems. This study
      examined sex differences in the association of urinary level of bisphenol-A (BPA)
      with selected indices of glucose homeostasis among U.S. adults. METHODS: Data
      analyses were performed using a sample of 1586 participants from the 2005 to 2008
      National Health and Nutrition Examination Surveys. BPA level and the ratio of BPA
      to-creatinine level were defined as log-transformed variables and in quartiles.
      Selected indices of glucose homeostasis were defined using fasting glucose and
      insulin data. Multivariate linear and logistic regression models for the
      hypothesized relationships were constructed after controlling for age, sex, race,
      education, marital status, smoking status, physical activity, total dietary
      intake, and urinary creatinine concentration. RESULTS: Taking the first quartile
      as a referent, the third quartile of BPA level was positively associated with log
      transformed level of insulin and beta-cell function (homeostasis model assessment
      for beta-cell function) as well as insulin resistance (log-transformed
      homeostasis model assessment for insulin resistance; homeostasis model assessment
      for insulin resistance >=2.5), with significant BPA-by-sex interaction; these
      associations were stronger among males than among females. Irrespective of sex,
      the ratio of BPA-to-creatinine level was not predictive of indices of glucose
      homeostasis. CONCLUSIONS: A complex association may exist between BPA and
      hyperinsulinemia among adult U.S. men. Prospective cohort studies are needed to
      further elucidate endocrine disruptors as determinants of adiposity-related
      disturbances.

PMID- 23954571
TI  - Imaging multiple biomarkers in captured rare cells by sequential immunostaining
      and photobleaching.
AB  - Several technologies recently have been developed for separating and counting
      circulating tumor cells (CTCs) in the human blood. CTCs play an important role in
      the metastasis of cancer. Most of the current applications are focused on the
      enumeration of CTCs; however, analysis of the enumerated CTCs has been proven to
      be increasingly important. Ensemble-decision aliquot ranking (eDAR) is a high
      throughput method that allows the isolation of the CTCs from the whole blood with
      high recovery and a zero false-positive rate. Coupling a CTC separation and
      capturing method, such as eDAR, with a downstream immunostaining test provides
      information about the cell's expression of certain protein biomarkers. In this
      article, we introduce a semi-automated system for sequential immunolabeling and
      photobleaching on the eDAR platform. With our new technique, we were able to
      evaluate the expression of eight different biomarkers on isolated CTCs. 

PMID- 23954566
TI  - Cow's milk allergy: from allergens to new forms of diagnosis, therapy and
      prevention.
AB  - The first adverse reactions to cow's milk were already described 2,000 years ago.
      However, it was only 50 years ago that several groups started with the analysis
      of cow's milk allergens. Meanwhile the spectrum of allergy eliciting proteins
      within cow's milk is identified and several cow's milk allergens have been
      characterized regarding their biochemical properties, fold and IgE binding
      epitopes. The diagnosis of cow's milk allergy is diverse ranging from fast and
      cheap in vitro assays to elaborate in vivo assays. Considerable effort was spent
      to improve the diagnosis from an extract-based into a component resolved concept.
      There is still no suitable therapy available against cow's milk allergy except
      avoidance. Therefore research needs to focus on the development of suitable and
      safe immunotherapies that do not elicit severe side effect.

PMID- 23954572
TI  - Primary squamous cell carcinoma of the vagina: prognostic factors, treatment
      patterns, and outcomes.
AB  - OBJECTIVE: Primary squamous cell carcinoma (SCCA) of the vagina is a rare
      malignancy with limited data to guide treatment. We evaluated prognostic factors
      and outcomes for patients with primary vaginal SCCA treated with definitive
      radiation therapy at a single institution. METHODS: A retrospective analysis was
      performed on patients treated for primary vaginal SCCA from 1959 to 2011.
      RESULTS: Ninety-one patients with primary vaginal SCCA were treated with
      definitive radiation therapy. Thirty-eight patients had FIGO stage I, 28 stage
      II, 13 stage III, and 12 stage IV disease. The mean total dose was 70.1 Gy. Two
      year overall survival (OS), locoregional control rate (LRC), and distant
      metastasis-free survival by stage were, respectively: stage I: 96.2%, 80.6%,
      87.5%; stage II: 92.3%, 64.7%, 84.6%; stage III: 66.6%, 44.4%, 50.0%; and stage
      IV: 25.0%, 14.3%, 25.0%. Treatment with total dose over 70 Gy was associated with
      improved OS (p=0.0956) and LRC (p=0.055). There was a significant difference in
      median dose received by patients who developed grade 3/4 toxicity compared to
      those who did not (82.9 Gy versus 70.0 Gy, p=0.0019). None of the 10 patients
      treated with IMRT experienced locoregional recurrence or grade 3/4 toxicity.
      Tumor size larger than 4 cm was associated with worse OS (p=0.0034) and LRC
      (p=0.006). CONCLUSIONS: Our analysis suggests that the optimal dose for
      definitive treatment of SCCA of the vagina lies between 70 and 80 Gy. Treatment
      with IMRT may allow for dose escalation with reduced toxicity and excellent LRC.
      Tumor size over 4 cm is associated with inferior outcomes and may require
      additional treatment modalities.

PMID- 23954573
TI  - Psoriasis patients exhibit impairment of the high potency CCR5(+) T regulatory
      cell subset.
AB  - CCR5 expression on CD4(+)CD25(high)Foxp3(+) regulatory T cells (Tregs) has been
      reported to be crucial for limiting Th1 inflammation associated with autoimmunity
      and bacterial infections. We inquired whether abnormalities in chemokine
      receptors expressed on Tregs might be involved in the psoriatic pathogenesis.
      Indeed, the proportion of CCR5(+) Treg was 58.8% in healthy individuals (n=9),
      whereas only half as many CCR5(+) Treg cells were found in psoriatic individuals
      (29.1%, n=8, p<0.01). The flow-enriched control CCR5(+) Tregs consistently
      exceeded the suppressive capacity of unsorted Tregs in autologous MLR assays
      (n=5, p<0.05) showing that CCR5(+) Treg subset is a high potency regulatory T
      cell population. Interestingly, psoriatic CCR5(+) Treg cells exhibited
      significantly less migratory capacity toward CCR5 ligands MIP-1beta and RANTES in
      vitro compared to CCR5(+) Treg controls (n=3, p<0.05). Our data demonstrate that
      psoriatic CCR5(+) Tregs cells are numerically-, functionally- and chemotactically
      deficient compared to controls and may pose a triple impairment on the ability of
      psoriatic Tregs to restrain inflammation. 

PMID- 23954574
TI  - Five-year clinical evaluation of zirconia-based bridges in patients in UK general
      dental practices.
AB  - OBJECTIVES: This study reported the results at 5 years of fixed-fixed all-ceramic
      bridges, constructed in a yttria oxide stabilized tetragonal zirconium oxide
      polycrystal (Y-TZP) substructure, placed in adult patients in UK general dental
      practices. MATERIALS AND METHODS: Four UK general dental practitioners recruited
      patients who required fixed bridgework and, after obtaining informed written
      consent, appropriate clinical and radiographic assessments were completed. The
      teeth were prepared and bridges constructed in accordance with the manufacturer's
      instructions. Each bridge was reviewed annually within 3 months of the
      anniversary of its placement by a calibrated examiner, together with the
      clinician who had placed the restoration, using modified USPHS criteria. RESULTS:
      Of the 41 bridges originally placed, 33 bridges were examined at 5 years. All Y
      TZP frameworks were intact and no bridge retainers had debonded. Eight chipping
      fractures in the veneering ceramic were noted over the 5-year period. In five
      cases the patients were unaware of these and these cases were polished. Of the
      remaining three cases, in one a repair was attempted but was unsuccessful, but
      the bridge remained in satisfactory service. However, in the case involving a
      chipping fracture of the mesial-incisal angle of a central incisor, it was
      considered that replacement of the bridge was necessary. CONCLUSION: 97% (n=32)
      of the 33 Lava Y-TZP fixed-fixed bridges, evaluated in patients attending UK
      general dental practices, were found to be performing satisfactorily. CLINICAL
      RELEVANCE: The use of Y-TZP frameworks holds promise.

PMID- 23954575
TI  - The inhibitory effect of a polymerisable cationic monomer on functional matrix
      metalloproteinases.
AB  - OBJECTIVES: This study examined the use of methacryloxylethyl cetyl dimethyl
      ammonium chloride (DMAE-CB) as a potential matrix metalloproteinases (MMPs)
      inhibitor on both soluble recombinant and dentine matrix-bound endogenous MMPs,
      meanwhile attempted to determine the effective anti-MMP group of quaternary
      ammonium methacrylates (QAMs). METHODS: The possible inhibitory effects of five
      DMAE-CB mass concentrations (0.1%, 0.5%, 1%, 3%, 5%) on soluble rhMMP-9 were
      measured using a colorimetic assay kit. Methyl methacrylate (MMA) and [2
      (methacryloyloxy)ethyl] trimethylammonium chloride (METMAC) were also screened
      against rhMMP-9 to compare the inhibitory effect with DMAE-CB. Matrix-bound
      endogenous MMP-activity was evaluated in completely demineralized dentine beams.
      Thirty beams were randomly divided into three groups (N=10) and respectively
      placed into 500MUL of calcium- and zinc-containing media (CM; control), 0.2%
      chlorhexidine or 3% DMAE-CB in CM aged for 30 days. The changes in modulus of
      elasticity, loss of dry mass and solubilization of collagen peptides were
      measured via three-point bending, precision weighing and hydroxyproline assay,
      respectively. RESULTS: 0.5-5% mass concentrations of DMAE-CB were highly
      effective (P<0.05) in inhibiting rhMMP-9 varied between 76.56+/-6.44% and 97.06+/
      3.24%, the inhibitory effect of MMA was much lower than that of METMAC and DMAE
      CB at the same concentration (P<0.05). Dentine beams incubated in 3% DMAE-CB
      showed only a 26.34% decrease in the modulus of elasticity (75.74% decrease in
      control), a 1.72+/-1.56% loss of dry mass (29.70+/-9.12% loss in control), and
      significantly less solubilized hydroxyproline when compared with the control
      (P<0.05). CONCLUSIONS: DMAE-CB is effective in inhibiting both soluble
      recombinant MMPs and matrix-bound dentine MMPs. Quaternary ammonium group is the
      effective anti-MMP group of QAMs. CLINICAL SIGNIFICANCE: The incorporation of
      DMAE-CB into dental adhesives has the potential to enhance the durability of
      dentine bonding and thus increases the longevity of restorations.

PMID- 23954576
TI  - Biocompatibility effects of indirect exposure of base-metal dental casting alloys
      to a human-derived three-dimensional oral mucosal model.
AB  - OBJECTIVES: The study employed a three-dimensional (3D) human-derived oral
      mucosal model to assess the biocompatibility of base-metal dental casting alloys
      ubiquitous in fixed prosthodontic and orthodontic dentistry. METHODS: Oral
      mucosal models were generated using primary human oral keratinocyte and gingival
      fibroblast cells seeded onto human de-epidermidised dermal scaffolds. Nickel
      chromium (Ni-Cr) and cobalt-chromium (Co-Cr) base-metal alloy immersion solutions
      were exposed to oral mucosal models for increasing time periods (2-72h). Analysis
      methodologies (histology, viable cell counts, oxidative stress, cytokine
      expression and toxicity) were performed following exposure. RESULTS: Ni-based
      alloy immersion solutions elicited significantly decreased cell viability
      (P<0.0004) with increased oxidative stress (P<0.0053), inflammatory cytokine
      expression (P<0.0077) and cellular toxicity levels (P<0.0001) compared with the
      controls. However, the Ni-free Co-Cr-based alloy immersion solutions did not
      elicit adverse oxidative stress (P>0.4755) or cellular toxicity (P<0.2339)
      responses compared with controls. CONCLUSIONS: Although the multiple analyses
      highlighted Ni-Cr base-metal alloy immersion solutions elicited significantly
      detrimental effects to the oral mucosal models, it was possible to distinguish
      between Ni-Cr alloys using the approach employed. The study employed a 3D human
      derived full-thickness differentiated oral mucosal model suitable for
      biocompatibility assessment of base-metal dental casting alloys through
      discriminatory experimental parameters. CLINICAL SIGNIFICANCE: Increasing
      incidences of Ni hypersensitivity in the general population warrants serious
      consideration from dental practitioners and patients alike where fixed
      prosthodontic/orthodontic dental treatments are the treatment modality involved.
      The novel and analytical oral mucosal model has the potential to significantly
      contribute to the advancement of reproducible dental medical device and dental
      material appraisals.

PMID- 23954577
TI  - Recontouring teeth and closing diastemas with direct composite buildups: a 5-year
      follow-up.
AB  - OBJECTIVES: Adhesive resin composite technology enables dentists to add composite
      material to tooth surfaces to close gaps and reshape tooth form without cavity
      preparation. This option creates new possibilities for minimally invasive
      dentistry as the tooth shape, position and colour can be altered without loss of
      tooth substance. However, evidence-based data on direct composite buildups are
      rare. METHODS: The purpose of this study was to evaluate the outcome and to
      document the occurrence of unfavourable events and clinical findings of 176
      direct composite buildups that had been performed in the Department of
      Conservative Dentistry, University Hospital Heidelberg, Germany, between 2002 and
      2008. Outcome was categorised as failure (F), survival (SR) or success (S).
      Restorations still in place and without prior failure at follow-up were
      qualitatively rated using modified USPHS/FDI criteria. RESULTS: During the follow
      up period, 30 restorations were found to have had unfavourable events or clinical
      findings. All restorations were repaired, and they remained in situ (SR). No
      complete loss (F) was recorded. The overall survival rate was 84.6% after 60
      months (95%, confidence interval [CI]: 78.5 and 90.6). Clinical quality was rated
      excellent or good for most (>90%) of the restorations examined. CONCLUSIONS: The
      direct composite buildups observed in this study were found to have promising
      clinical outcome and good quality parameters after 5 years. If a noninvasive or
      minimally invasive treatment approach is indicated, direct composite buildups
      provide an acceptable treatment alternative for the aesthetic correction and
      reshaping of anterior teeth. CLINICAL SIGNIFICANCE: The application of direct
      composite buildups in clinical cases in which a non- or minimally invasive
      treatment approach is indicated provides an excellent treatment alternative for
      gold-standard treatment options like laboratory-made crowns and porcelain
      veneers. Restorations in the present investigation showed a functional survival
      rate of 100%, an overall survival rate of 84.6% after 5 years.

PMID- 23954578
TI  - Hendra and Nipah infection: emerging paramyxoviruses.
AB  - Since their first emergence in mid 1990s henipaviruses continued to re emerge in
      Australia and South East Asia almost every year. In total there has been more
      than 12 Nipah and 48 Hendra virus outbreaks reported in South East Asia and
      Australia, respectively. These outbreaks are associated with significant economic
      and health damages that most high risks countries (particularly in South East
      Asia) cannot bear the burden of such economical threats. Up until recently, there
      were no actual therapeutics available to treat or prevent these lethal
      infections. However, an international collaborative research has resulted in the
      identification of a potential equine Hendra vaccine capable of providing antibody
      protection against Hendra virus infections. Consequently, with the current
      findings and after nearly 2 decades since their first detection, are we there
      yet? This review recaps the chronicle of the henipavirus emergence and briefly
      evaluates potential anti-henipavirus vaccines and antivirals.

PMID- 23954579
TI  - Extent of HCV NS3 protease variability and resistance-associated mutations
      assessed by next generation sequencing in HCV monoinfected and HIV/HCV coinfected
      patients.
AB  - HCV quasispecies variability represents the background for the selection of
      mutations and for the development of drug resistance. Natural aminoacid changes
      in NS3, associated with reduced protease inhibitor susceptibility, have been
      observed in treatment-naive patients. Massively parallel sequencing has been used
      to analyze NS3 quasispecies in patients infected with HCV genotype 1, naive to
      anti-HCV treatment, with/without HIV-coinfection, to establish the genetic
      heterogeneity and the presence of amino acid substitutions at positions
      responsible for drug resistance. Genomes carrying substitutions represented
      either predominant or minority components of viral quasispecies, and were
      observed in 85.7% of patients. Multiple substitutions, frequently associated on
      the same haplotype, were observed in 46.4% of patients. High resistance
      combinations were not detected, neither on the same genome, nor in the whole
      quasispecies. Heterogeneity of HCV NS3 was lower in HIV-coinfected as compared to
      HCV-monoinfected patients, but factors underlying this difference remain to be
      established. Although the relevance of naturally occurring mutations with respect
      of resistance development and probability of success of direct acting antivirals
      is questioned, UDPS may be beneficial to help understanding viral dynamics,
      providing high resolution view of viral diversity.

PMID- 23954580
TI  - Transmission of influenza A/H5N1 viruses in mammals.
AB  - Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans and
      cause severe respiratory disease and fatalities. Currently, these viruses are not
      efficiently transmitted from person to person, although limited human-to-human
      transmission may have occurred. Nevertheless, further adaptation of avian H5N1
      influenza A viruses to humans and/or reassortment with human influenza A viruses
      may result in aerosol transmissible viruses with pandemic potential. Although the
      full range of factors that modulate the transmission and replication of influenza
      A viruses in humans are not yet known, we are beginning to understand some of the
      molecular changes that may allow H5N1 influenza A viruses to transmit via
      aerosols or respiratory droplets among mammals. A better understanding of the
      biological basis and genetic determinants that confer transmissibility to H5N1
      influenza A viruses in mammals is important to enhance our pandemic preparedness.

PMID- 23954581
TI  - Radical prostatectomy improves and prevents age dependent progression of lower
      urinary tract symptoms.
AB  - PURPOSE: The prevalence of lower urinary tract symptoms increases with age and
      impairs quality of life. Radical prostatectomy has been shown to relieve lower
      urinary tract symptoms at short-term followup but the long-term effect of radical
      prostatectomy on lower urinary tract symptoms is unclear. MATERIALS AND METHODS:
      We performed a prospective cohort study of 1,788 men undergoing radical
      prostatectomy. The progression of scores from the self-administered AUASS
      (American Urological Association symptom score) preoperatively, and at 3, 6, 12,
      24, 48, 60, 84, 96 and 120 months was analyzed using models controlling for
      preoperative AUASS, age, prostate specific antigen, pathological Gleason score
      and stage, nerve sparing, race and marital status. This model was also applied to
      patients stratified by baseline clinically significant (AUASS greater than 7) and
      insignificant (AUASS 7 or less) lower urinary tract symptoms. RESULTS: Men
      exhibited an immediate worsening of lower urinary tract symptoms that improved
      between 3 months and 2 years after radical prostatectomy. Overall the difference
      between mean AUASS at baseline and at 10 years was not statistically or
      clinically significant. Men with baseline clinically significant lower urinary
      tract symptoms experienced immediate improvements in lower urinary tract symptoms
      that lasted until 10 years after radical prostatectomy (13.5 vs 8.81, p <0.001).
      Men with baseline clinically insignificant lower urinary tract symptoms
      experienced a statistically significant but clinically insignificant increase in
      mean AUASS after 10 years (3.09 to 4.94, p <0.001). The percentage of men with
      clinically significant lower urinary tract symptoms decreased from baseline to 10
      years after radical prostatectomy (p = 0.02). CONCLUSIONS: Radical prostatectomy
      is the only treatment for prostate cancer shown to improve and prevent the
      development of lower urinary tract symptoms at long-term followup. This
      previously unrecognized long-term benefit argues in favor of the prostate as the
      primary contributor to male lower urinary tract symptoms.

PMID- 23954582
TI  - Intravaginal and subcutaneous immunization induced vaccine specific CD8 T cells
      and tumor regression in the bladder.
AB  - PURPOSE: Vaccines targeting tumor associated antigens are in development for
      bladder cancer. Most of these cancers are nonmuscle invasive at diagnosis and
      confined in the mucosa and submucosa. However, to our knowledge how vaccination
      may induce the regression of tumors at such mucosal sites has not been examined
      previously. We compared different immunization routes for the ability to induce
      vaccine specific antitumor CD8 T cells in the bladder and bladder tumor
      regression in mice. MATERIALS AND METHODS: In the absence of a murine bladder
      tumor model expressing a tumor antigen relevant for human use we established an
      orthotopic model expressing the HPV-16 tumor antigen E7 as a model. We used an
      adjuvant E7 polypeptide to induce CD8 T cell mediated tumor regression. RESULTS:
      Subcutaneous and intravaginal but not intranasal vaccination induced a high
      number of TetE7(+)CD8(+) T cells in the bladder as well as bladder tumor
      regression. The entry of vaccine specific T cells in the bladder was not the only
      key since persistent regression of established bladder tumors by intravaginal or
      subcutaneous immunization was associated with tumor infiltration of total CD4 and
      CD8 T cells. This resulted in an increase in TetE7(+)CD8(+) T cells and a
      decrease in T regulatory cells, leading to an increased number of effector
      interferon-gamma secreting vaccine specific CD8 T cells in the regressing bladder
      tumor. CONCLUSIONS: These data show that immunization routes should be tailored
      to each mucosal tumor site. Subcutaneous or intravaginal vaccination may be of
      additional value to treat patients with bladder cancer.

PMID- 23954583
TI  - Outcomes of incontinent ileovesicostomy in the pediatric patient.
AB  - PURPOSE: Ileovesicostomy is a reconstructive option in complex urological cases
      but pediatric specific outcomes are lacking. We report our results with pediatric
      ileovesicostomy. MATERIALS AND METHODS: We retrospectively evaluated patients
      younger than 18 years undergoing incontinent ileovesicostomy at Vanderbilt
      University. History, urinary tract management and operative course were reviewed
      in the electronic medical record. Particular attention was given to immediate and
      long-term postoperative complications. RESULTS: Nine patients underwent
      incontinent ileovesicostomy between 2000 and 2013 at a mean age of 10.3 years
      (range 1.4 to 15.5). Surgical indication was sequelae of neurogenic or
      nonneurogenic neurogenic bladder (such as infection or worsening hydronephrosis)
      in 5 patients, reversal of vesicostomy in 3 and closure of cloacal exstrophy in
      1. All 9 patients were thought incapable of reliable clean intermittent
      catheterization due to family unwillingness, poor social support or patient
      refusal. Median followup was 11.5 months (mean 48.2, range 1.3 to 144.8).
      Immediate postoperative complications included ileus requiring total parenteral
      nutrition and a wound infection in 1 patient. Long-term complications included
      urinary tract infection in 2 patients (febrile in 1 and positive culture for foul
      smelling urine in 1), stomal issues in 2 and temporary urethral leakage in 1.
      Constipation affected 3 children in long-term followup (all with neurogenic bowel
      preoperatively). Postoperative creatinine was stable or improved in all patients.
      CONCLUSIONS: Ileovesicostomy is a viable approach in children left with few other
      options, particularly those who are noncompliant or physically/socially unable to
      handle catheterization. This operation can help keep such patients out of
      diapers.

PMID- 23954584
TI  - Risk factors and predictors of severity score and complications of pediatric
      hemorrhagic cystitis.
AB  - PURPOSE: We retrospectively analyzed our institutional incidence of hemorrhagic
      cystitis, identified risk factors, and examined associations of risk factors with
      disease severity and genitourinary complication rates. MATERIALS AND METHODS: We
      reviewed charts of all consecutive pediatric patients treated from 1986 to 2010.
      We analyzed demographics, underlying diagnosis and treatment data to assess risk
      factors for hemorrhagic cystitis. We also correlated disease severity scores with
      clinical predisposing factors, and performed univariate and multivariate analyses
      to examine associations between risk factors and outcomes. RESULTS: Hemorrhagic
      cystitis was observed in 97 of 6,119 children (1.6%), most of whom (75%) had
      severity scores of II or III. Mean +/- SD age was 12.2 +/- 6.3 years for patients
      with hemorrhagic cystitis and 10.5 +/- 7 years for patients without hemorrhagic
      cystitis (p = 0.017). On univariate analysis increased risk of hemorrhagic
      cystitis was significantly associated with age greater than 5 years, male gender,
      cyclophosphamide or busulfan chemotherapy, bone marrow or peripheral blood stem
      cell transplantation, pelvic radiotherapy and underlying diagnoses of
      rhabdomyosarcoma, acute leukemia and aplastic anemia. On multivariate analysis
      age greater than 5 years, allogeneic bone marrow or peripheral blood stem cell
      transplantation and pelvic radiotherapy were significantly associated with
      increased risk of hemorrhagic cystitis. Older age, late onset hemorrhagic
      cystitis, positive urine culture for BK virus and bone marrow or peripheral blood
      stem cell transplantation were associated with greater disease severity. Patients
      with higher severity scores more frequently experienced bladder perforation,
      hydronephrosis, overall hemorrhagic cystitis complications, and increased
      creatinine and blood urea nitrogen levels during followup. CONCLUSIONS: Older
      age, previous bone marrow or peripheral blood stem cell transplantation and BK
      virus in the urine are risk factors for hemorrhagic cystitis and are associated
      with a higher severity score. Higher severity scores are associated with
      increased rates of genitourinary complications and renal impairment.

PMID- 23954585
TI  - Volumetric in vivo visualization of upper urinary tract tumors using optical
      coherence tomography: a pilot study.
AB  - PURPOSE: Knowledge of tumor stage and grade is paramount for treatment decision
      making in cases of upper urinary tract urothelial carcinoma but this condition
      cannot be accurately assessed by current techniques. Optical coherence tomography
      can hypothetically provide the urologist with real-time intraoperative
      information on tumor grade and stage. In this pilot study we report what are to
      our knowledge the first results of optical coherence tomography for grading and
      staging upper urinary tract urothelial carcinoma. MATERIALS AND METHODS: Eight
      consecutive patients underwent ureterorenoscopy for suspicion or followup of
      upper urinary tract urothelial carcinoma. Optical coherence tomography data sets
      were intraoperatively obtained from the ureter and renal pelvis. All patients
      eventually underwent nephroureterectomy. Optical coherence tomography staging was
      done by visual inspection of lesions found on optical coherence tomography
      images. Optical coherence tomography grading was done by quantifying optical
      coherence tomography signal attenuation in mm(-1) on lesions and comparing
      results with the histopathological diagnosis. The Wilcoxon rank sum test was used
      for statistical analysis. RESULTS: For 7 in vivo optical coherence tomography
      diagnoses staging was in accordance with histology. In patient 8 tumor thickness
      transcended optical coherence tomography imaging depth range and, therefore,
      invasiveness findings were inconclusive. For grading the median attenuation
      coefficient for grade 2 and 3 lesions was 1.97 (IQR 1.57-2.30) and 3.53 mm(-1)
      (IQR 2.74-3.94), respectively (p<0.001). Healthy urothelium was too thin to
      reliably determine the attenuation coefficient. CONCLUSIONS: Optical coherence
      tomography is a promising, minimally invasive tool for real-time intraoperative
      optical diagnosis of tumors in the upper urinary tract. Our results warrant
      future research in a larger sample size to determine the accuracy of grading and
      staging by optical coherence tomography, and its possible implementation in the
      diagnostic algorithm for upper urinary tract urothelial carcinoma.

PMID- 23954586
TI  - Effect of cholesterol content on the structural and dynamic membrane properties
      of DMPC/DSPC large unilamellar bilayers.
AB  - In this study, we report the effect of cholesterol content on the dynamic and
      structural properties of a dimyristoyl-phosphatidylcholine and distearoyl
      phosphatidylcholine mixture in large unilamellar vesicles. The range of
      cholesterol concentrations studied varied around approximately 33.3mol%, where it
      has been postulated that an abrupt change in bilayer organization occurs. Steady
      state fluorescence measurements demonstrated a typical behavior; at low
      temperatures in the main phase transition, the cholesterol concentration did not
      affect the gel phase, but at 37.5 degrees C (phase coexistence) and in the liquid
      crystalline phase, the presence of cholesterol produced an increase in the
      fluorescence anisotropy of DPH and the generalized polarization of Laurdan. The
      greater effect was observed in the liquid crystalline phase, in which the bilayer
      became a mixture of fluid-like and liquid-ordered phases. The results obtained at
      approximately 33.3mol% of Cholesterol demonstrated that the Generalized
      Polarization of Laurdan, the DPH lifetime, the limiting anisotropy and the
      rotational correlation time, as well as the fluorescence quenching of DPH by
      TEMPO, are at maxima, while the fluorescence intensity of dehydroergosterol and
      the lipid solubility in TritonX-100 are at minima. These results correlate well
      with the hypothesis of domain segregation in the DMPC/DSPC/Cholesterol LUV
      system. In this context, we postulate that at 33.3mol% of Cho, the proportion of
      ordered domains reaches a maximum. 

PMID- 23954587
TI  - Structural effects of the Solanum steroids solasodine, diosgenin and solanine on
      human erythrocytes and molecular models of eukaryotic membranes.
AB  - This report presents evidence that the following Solanum steroids: solasodine,
      diosgenin and solanine interact with human erythrocytes and molecular models of
      their membranes as follows: a) X-ray diffraction studies showed that the
      compounds at low molar ratios (0.1-10.0mol%) induced increasing structural
      perturbation to dimyristoylphosphatidylcholine bilayers and to a considerable
      lower extent to those of dimyristoylphosphatidylethanolamine; b) differential
      scanning calorimetry data showed that the compounds were able to alter the
      cooperativity of dimyristoylphosphatidylcholine,
      dimyristoylphosphatidylethanolamine and dimyristoylphosphatidylserine phase
      transitions in a concentration-dependent manner; c) in the presence of steroids,
      the fluorescence of Merocyanine 540 incorporated to the membranes decreased
      suggesting a fluidization of the lipid system; d) scanning electron microscopy
      observations showed that all steroids altered the normal shape of human
      erythrocytes inducing mainly echinocytosis, characterized by the formation of
      blebs in their surfaces, an indication that their molecules are located into the
      outer monolayer of the erythrocyte membrane. 

PMID- 23954588
TI  - The sticholysin family of pore-forming toxins induces the mixing of lipids in
      membrane domains.
AB  - Sticholysins (Sts) I and II (StI/II) are pore-forming toxins (PFTs) produced by
      the Caribbean Sea anemone Stichodactyla helianthus belonging to the actinoporin
      family, a unique class of eukaryotic PFTs exclusively found in sea anemones. The
      role of lipid phase co-existence in the mechanism of the action of membranolytic
      proteins and peptides is not clearly understood. As for actinoporins, it has been
      proposed that phase separation promotes pore forming activity. However little is
      known about the effect of sticholysins on the phase separation of lipids in
      membranes. To gain insight into the mechanism of action of sticholysins, we
      evaluated the effect of these proteins on lipid segregation using differential
      scanning calorimetry (DSC) and atomic force microscopy (AFM). New evidence was
      obtained reflecting that these proteins reduce line tension in the membrane by
      promoting lipid mixing. In terms of the relevance for the mechanism of action of
      actinoporins, we hypothesize that expanding lipid disordered phases into lipid
      ordered phases decreases the lipid packing at the borders of the lipid raft,
      turning it into a more suitable environment for N-terminal insertion and pore
      formation. 

PMID- 23954589
TI  - Quantitation of zoledronic acid in murine bone by liquid chromatography coupled
      with tandem mass spectrometry.
AB  - An in vitro method for extraction and quantification of zoledronic acid (ZA) from
      murine bone was developed. Whole mouse bones were incubated in ZA solutions with
      predetermined concentrations and bound ZA was subsequently extracted from bone
      with phosphoric acid and derivatized using trimethylsilyl diazomethane (TMS-DAM).
      ZA tetra-methyl phosphonate was quantified by liquid chromatography coupled with
      tandem mass spectrometry (LC/MS/MS). This resulted in a sensitive, accurate, and
      precise method that was linear over three orders of magnitude (0.0250-50.0MUg/mL
      ZA). For quality control (QC) samples, intra-and inter-day coefficients of
      variance were calculated and were less than 10%. This method was then applied to
      an in vivo model to quantitate ZA from the femur and mandible of three mice
      treated with ZA for two weeks. The mean ZA extracted from the mandible was four
      fold higher than that extracted from the femur (3.06+/-0.52 vs. 0.76+/-0.09ng/mg,
      respectively) indicating that ZA did not distribute equally in the skeleton and
      had a preference to the mandible. In conclusion, a highly sensitive method to
      measure ZA from mouse skeleton was developed, which can be easily adapted to
      multiple mammalian models including humans receiving ZA treatment. 

PMID- 23954590
TI  - Hedgehog pathway modulation by multiple lipid binding sites on the smoothened
      effector of signal response.
AB  - Hedgehog (Hh) signaling during development and in postembryonic tissues requires
      activation of the 7TM oncoprotein Smoothened (Smo) by mechanisms that may involve
      endogenous lipidic modulators. Exogenous Smo ligands previously identified
      include the plant sterol cyclopamine (and its therapeutically useful synthetic
      mimics) and hydroxylated cholesterol derivatives (oxysterols); Smo is also highly
      sensitive to cellular sterol levels. The relationships between these effects are
      unclear because the relevant Smo structural determinants are unknown. We identify
      the conserved extracellular cysteine-rich domain (CRD) as the site of action for
      oxysterols on Smo, involving residues structurally analogous to those contacting
      the Wnt lipid adduct in the homologous Frizzled CRD; this modulatory effect is
      distinct from that of cyclopamine mimics, from Hh-mediated regulation, and from
      the permissive action of cellular sterol pools. These results imply that Hh
      pathway activity is sensitive to lipid binding at several Smo sites, suggesting
      mechanisms for tuning by multiple physiological inputs. 

PMID- 23954592
TI  - Unsupervised biomedical named entity recognition: experiments with clinical and
      biological texts.
AB  - Named entity recognition is a crucial component of biomedical natural language
      processing, enabling information extraction and ultimately reasoning over and
      knowledge discovery from text. Much progress has been made in the design of rule
      based and supervised tools, but they are often genre and task dependent. As such,
      adapting them to different genres of text or identifying new types of entities
      requires major effort in re-annotation or rule development. In this paper, we
      propose an unsupervised approach to extracting named entities from biomedical
      text. We describe a stepwise solution to tackle the challenges of entity boundary
      detection and entity type classification without relying on any handcrafted
      rules, heuristics, or annotated data. A noun phrase chunker followed by a filter
      based on inverse document frequency extracts candidate entities from free text.
      Classification of candidate entities into categories of interest is carried out
      by leveraging principles from distributional semantics. Experiments show that our
      system, especially the entity classification step, yields competitive results on
      two popular biomedical datasets of clinical notes and biological literature, and
      outperforms a baseline dictionary match approach. Detailed error analysis
      provides a road map for future work. 

PMID- 23954591
TI  - IGF-1 activates a cilium-localized noncanonical Gbetagamma signaling pathway that
      regulates cell-cycle progression.
AB  - Primary cilia undergo cell-cycle-dependent assembly and disassembly. Emerging
      data suggest that ciliary resorption is a checkpoint for S phase reentry and that
      the activation of phospho(T94)Tctex-1 couples these two events. However, the
      environmental cues and molecular mechanisms that trigger these processes remain
      unknown. Here, we show that insulin-like growth-1 (IGF-1) accelerates G1-S
      progression by causing cilia to resorb. The mitogenic signals of IGF-1 are
      predominantly transduced through IGF-1 receptor (IGF-1R) on the cilia of
      fibroblasts and epithelial cells. At the base of the cilium, phosphorylated IGF
      1R activates an AGS3-regulated Gbetagamma signaling pathway that subsequently
      recruits phospho(T94)Tctex-1 to the transition zone. Perturbing any component of
      this pathway in cortical progenitors induces premature neuronal differentiation
      at the expense of proliferation. These data suggest that during corticogenesis, a
      cilium-transduced, noncanonical IGF-1R-Gbetagamma-phospho(T94)Tctex-1 signaling
      pathway promotes the proliferation of neural progenitors through modulation of
      ciliary resorption and G1 length. 

PMID- 23954593
TI  - Prostatic adenocarcinoma metastatic to bone.

PMID- 23954594
TI  - Editorial comment.

PMID- 23954595
TI  - Clinical significance of tumor volume in endometrial cancer: a Japan-Korea
      cooperative study.
AB  - OBJECTIVE: The aim of this study was to elucidate the significance of tumor
      volume as a risk factor for predicting lymph node metastasis. METHODS: We applied
      the tumor volume index to the data that were collected for 327 Korean patients
      with endometrial cancer who underwent preoperative assessment including magnetic
      resonance imaging (MRI) and subsequent surgery including systematic
      lymphadenectomy. The volume index, which we previously reported in the
      literature, was defined as the product of maximum longitudinal diameter along the
      uterine axis, maximum anteroposterior diameter in a sagittal section image, and
      maximum horizontal diameter in a horizontal section image according to MRI data,
      from 425 Japanese women with endometrial cancer. Relationships between lymph node
      metastasis and results of preoperative examinations including volume index were
      analyzed by logistic regression analysis. RESULTS: The prevalence of affected
      lymph nodes was 14.2%. Multivariate analysis showed that high-grade histology
      assessed by endometrial biopsy [odds ratio (OR); 2.9, 95% confidence interval
      (CI): 1.4-6.4], volume index (OR; 2.4, 95% CI: 1.1-5.3), node enlargement
      assessed by MRI (OR; 4.2, 95% CI: 1.4-13.2), and high serum cancer antigen
      (CA)125 level (OR; 3.6, 95% CI: 1.6-8.1) were significantly and independently
      related to lymph node metastasis. When volume index was excluded from the
      analysis, myoinvasion assessed by MRI was an independent risk factor for lymph
      node metastasis as well as high-grade histology, node enlargement, and high serum
      CA125 level. CONCLUSION: Volume index is compatible with myometrial invasion as a
      factor for predicting lymph node metastasis in endometrial cancer.

PMID- 23954596
TI  - The crystal structure and biochemical properties of DHBPS from Streptococcus
      pneumoniae, a potential anti-infective target for Gram-positive bacteria.
AB  - The enzymes involved in riboflavin biosynthesis are considered to be potential
      anti-bacterial drug targets because these proteins are essential in bacterial
      pathogens but are absent in humans. 3,4-dihydroxy-2-butanone-4-phosphate synthase
      (DHBPS) is one of the key enzymes in the biosynthesis of riboflavin. DHBPS
      catalyzes the conversion of ribulose-5-phosphate (Ru5P) to 3,4-Dihydroxy-2
      butanone-4-phosphate (DHBP) and formate. The purified SpDHBPS enzyme, in the
      presence of Mg(2+) ion, catalyzed the conversion of Ru5P to DHBP at a rate of
      109nmolmin(-1)mg(-1) with an apparent Km value of 181MUM at 37 degrees C.
      Surprisingly, our experiments first revealed that DHBPS showed activity in the
      presence of the trivalent metal ion, Fe(3+). Furthermore, we determined the
      crystal structure of DHBPS from Gram-positive bacteria, Streptococcus pneumoniae,
      with 2.0A resolution. The overall architecture of SpDHBPS was similar to its
      homologs, which comprise one beta-sheet (five-stranded) and eight alpha-helices,
      adopting a three-layered alpha-beta-alpha sandwich fold. Similar to the homologs,
      gel-filtration experiments verified that the enzyme was arranged as a dimer.
      Although the overall fold of DHBPS was similar, the significant structural
      differences between the species at the active site region may be utilized to
      develop antibacterial agents that are species-specific. 

PMID- 23954597
TI  - Mitochondrial calcium uniporter opener spermine attenuates the cerebral
      protection of diazoxide through apoptosis in rats.
AB  - BACKGROUND: It is reported that ischemic penumbra is a dynamic process, in which
      irreversible necrosis in the center of ischemia propagates to the neighboring
      tissue over time. Recent research has indicated that mitochondrial adenosine
      triphosphate (ATP)-sensitive potassium channels (mitoKATP) opener diazoxide plays
      an important role in cerebral protection; however, the role of mitochondrial
      calcium uniporter (MCU) in the effect of diazoxide on penumbra and infarct core
      remains unclear. METHODS: Adult male Wistar rats were randomly divided into 5
      groups: the Sham group, the ischemia-reperfusion (I/R) group, the diazoxide and
      ischemia-reperfusion (Dzx + I/R) group, the diazoxide and spermine and ischemia
      reperfusion (Dzx + Sper + I/R) group, and the spermine and ischemia-reperfusion
      (Sper + I/R) group. The animals were exposed to 24-hour reperfusion after 2-hour
      ischemia. Diazoxide and spermine were administrated at 30 minutes or 10 minutes
      before the beginning of ischemia or reperfusion, respectively. After 24-hour
      reperfusion, animals were given neurologic performance tests and when overdosed
      with general anesthesia their brains were excised for infarct volume, apoptosis,
      and immunohistochemical. RESULTS: Rats in the Dzx + I/R group displayed improved
      neurologic deficits, decreased infarct volume in cortex but not in subcortex, and
      apoptosis (evidenced by decreased terminal deoxynucleotidyl transferase-mediated
      dUTP nick end lebeling-positive percentage and the immunohistochemistry of
      cytochrome c) in cortex caused by ischemia/reperfusion. Rats in the Dzx + Sper +
      I/R group displayed worse neurologic deficits, larger infarct volume in cortex
      but not in subcortex, and more apoptosis both in penumbra and infarct core of
      cortex than those in the Dzx + I/R group. CONCLUSIONS: Results in our study
      suggested that diazoxide improved neurologic deficits, decreased infarct volume
      in cortex but not in subcortex, and apoptosis in cortex against
      ischemia/reperfusion injury is mediated by spermine.

PMID- 23954598
TI  - Costs of hospitalization for stroke patients aged 18-64 years in the United
      States.
AB  - BACKGROUND: Estimates for the average cost of stroke have varied 20-fold in the
      United States. To provide a robust cost estimate, we conducted a comprehensive
      analysis of the hospitalization costs for stroke patients by diagnosis status and
      event type. METHODS: Using the 2006-2008 MarketScan inpatient database, we
      identified 97,374 hospitalizations with a primary or secondary diagnosis of
      stroke. We analyzed the costs after stratifying the hospitalizations by stroke
      type (hemorrhagic, ischemic, and other strokes) and diagnosis status (primary and
      secondary). We employed regressions to estimate the impact of event type and
      diagnosis status on costs while controlling for major potential confounders.
      RESULTS: Among the 97,374 hospitalizations (average cost: $20,396 +/- $23,256),
      the number with ischemic, hemorrhagic, or other strokes was 62,637, 16,331, and
      48,208, respectively, with these types having average costs, in turn, of $18,963
      +/- $21,454, $32,035 +/- $32,046, and $19,248 +/- $21,703. A majority (62%) of
      the hospitalizations had stroke listed as a secondary diagnosis only. Regression
      analysis found that, overall, hemorrhagic stroke cost $14,499 more than ischemic
      stroke (P < .001). For hospitalizations with a primary diagnosis of ischemic
      stroke, those with a secondary diagnosis of ischemic heart disease (IHD) had
      costs that were $9836 higher (P < .001) than those without IHD. CONCLUSIONS: The
      costs of hospitalizations involving stroke are high and vary greatly by type of
      stroke, diagnosis status, and comorbidities. These findings should be
      incorporated into cost-effective strategies to reduce the impact of stroke.

PMID- 23954599
TI  - Infections present on admission compared with hospital-acquired infections in
      acute ischemic stroke patients.
AB  - BACKGROUND: To date, few studies have assessed the influence of infections
      present on admission (POA) compared with hospital-acquired infections (HAIs) on
      neurologic deterioration (ND) and other outcome measures in acute ischemic stroke
      (AIS). METHODS: Patients admitted with AIS to our stroke center (July 2010 to
      December 2010) were retrospectively assessed. The following infections were
      assessed: urinary tract infection, pneumonia, and bacteremia. Additional chart
      review was performed to determine whether the infection was POA or HAI. We
      assessed the relationship between infections in ischemic stroke patients and
      several outcome measures including ND and poor functional outcome. A mediation
      analysis was performed to assess the indirect effects of HAI, ND, and poor
      functional outcome. RESULTS: Of the 334 patients included in this study, 77 had
      any type of infection (23 POA). After adjusting for age, National Institutes of
      Health Stroke Scale at baseline, glucose on admission, and intravenous tissue
      plasminogen activator, HAI remained a significant predictor of ND (odds ratio
      [OR]=8.8, 95% confidence interval [CI]: 4.2-18.7, P<.0001) and poor functional
      outcome (OR=41.7, 95% CI: 5.2-337.9, P=.005), whereas infections POA were no
      longer associated with ND or poor functional outcome. In an adjusted analysis, we
      found that 57% of the effect from HAI infections on poor functional outcome is
      because of mediation through ND (P<.0001). CONCLUSIONS: Our data suggests that
      HAI in AIS patients increases the odds of experiencing ND and subsequently
      increases the odds of being discharged with significant disability. This mediated
      effect suggests a preventable cause of ND that can thereby decrease the odds of
      poor functional outcomes after an AIS.

PMID- 23954600
TI  - Stroke mimics under the drip-and-ship paradigm.
AB  - BACKGROUND: Recent reports suggested better outcomes associated with the drip-and
      ship paradigm for acute ischemic stroke (AIS) treated with thrombolysis. We
      hypothesized that a higher rate of stroke mimics (SM) among AIS treated in
      nonspecialized stroke centers that are transferred to comprehensive centers is
      responsible for such outcomes. METHODS: Consecutive patients treated with
      thrombolysis according to the admission criteria were reviewed in a single
      comprehensive stroke center over 1 academic year (July 1, 2011 to June 30, 2012).
      Information on the basic demographic, hospital complications, psychiatric
      diagnoses, and discharge disposition was collected. We identified those patients
      who were treated at a facility and then transferred to the tertiary center (ie,
      drip-and-ship paradigm). In addition to comparative and adjusted analysis to
      identify predictors for SM, a stratified analysis by the drip-and-ship status was
      performed. RESULTS: One hundred twenty patients were treated with thrombolysis
      for AIS included in this analysis; 20 (16.7%) were discharged with the final
      diagnosis of SM; 14 of those had conversion syndrome and 6 patients had other
      syndromes (seizures, migraine, and hypoglycemia). Patients with SM were younger
      (55.6 +/- 15.0 versus 69.4 +/- 14.9, P = .0003) and more likely to harbor
      psychiatric diagnoses (45% versus 9%; P <= .0001). Eighteen of 20 SM patients
      (90%) had the drip-and-ship treatment paradigm compared with 65% of those with
      AIS (P = .02). None of the SM had hemorrhagic complications, and all were
      discharged to home. Predictors of SM on adjusted analysis included the drip-and
      ship paradigm (odds ratio [OR] 12.8, 95% confidence interval [CI] 1.78, 92.1) and
      history of any psychiatric illness (OR 12.08; 95% CI 3.14, 46.4). Eighteen of 83
      drip-and-ship patients (21.7%) were diagnosed with SM compared with 2 of 37
      patients (5.4%) presented directly to the hub hospital (P = .02). CONCLUSION: The
      drip-and-ship paradigm and any psychiatric history predict the diagnosis of SM.
      None of the SM had thrombolysis-related complications, and all were discharged to
      home. These findings may explain the superior outcomes associated with the drip
      and-ship paradigm in the treatment for AIS.

PMID- 23954601
TI  - Early and continuous neurologic improvements after intravenous thrombolysis are
      strong predictors of favorable long-term outcomes in acute ischemic stroke.
AB  - BACKGROUND: Intravenously administered tissue plasminogen activator (IV tPA)
      remains the only approved therapeutic agent for arterial recanalization in acute
      ischemic stroke (AIS). Considerable proportion of AIS patients demonstrate
      changes in their neurologic status within the first 24 hours of intravenous
      thrombolysis with IV tPA. However, there are little available data on the course
      of clinical recovery in subacute 2- to 24-hour window and its impact. We
      evaluated whether neurologic improvement at 2 and 24 hours after IV tPA bolus can
      predict functional outcomes in AIS patients at 3 months. METHODS: Data for
      consecutive AIS patients treated with IV tPA within 4.5 hours of symptom onset
      during 2007-2011 were prospectively entered in our thrombolyzed registry.
      National Institutes of Health Stroke Scale (NIHSS) scores were recorded before IV
      tPA bolus, at 2 and 24 hours. Early neurologic improvement (ENI) at 2 hours was
      defined as a reduction in NIHSS score by 10 or more points from baseline or an
      absolute score of 4 or less points at 2 hours. Continuous neurologic improvement
      (CNI) was defined as a reduction of NIHSS score by 8 or more points between 2 and
      24 hours or an absolute score of 4 or less points at 24 hours. Favorable
      functional outcomes at 3 months were determined by modified Rankin Scale (mRS)
      score of 0-1. RESULTS: Of 2460 AIS patients admitted during the study period, 263
      (10.7%) received IV tPA within the time window; median age was 64 years (range 19
      92), with 63.9% being men, a median NIHSS score of 17 points (range 5-35), and a
      median onset-to-treatment time of 145 minutes (range 57-270). Overall, 130
      (49.4%) thrombolyzed patients achieved an mRS score of 0-1 at 3 months. The
      female gender, age, and baseline NIHSS score were found to be significantly
      associated with CNI on univariate analysis. On multivariate analysis, NIHSS score
      at onset and female gender (odds ratio [OR]: 2.218, 95% confidence interval [CI]:
      1.140-4.285; P=.024) were found to be independent predictors of CNI. Factors
      associated with favorable outcomes at 3 months on univariate analysis were
      younger age, female gender, hypertension, NIHSS score at onset, recanalization on
      transcranial Doppler (TCD) monitoring or repeat computed tomography (CT)
      angiography, ENI at 2 hours, and CNI. On multivariate analysis, NIHSS score at
      onset (OR per 1-point increase: .835, 95% CI: .751-.929, P<.001), 2-hour TCD
      recanalization (OR: 3.048, 95% CI: 1.537-6.046; P=.001), 24-hour CT angiographic
      recanalization (OR: 4.329, 95% CI: 2.382-9.974; P=.001), ENI at 2 hours (OR:
      2.536, 95% CI: 1.321-5.102; P=.004), and CNI (OR: 7.253, 95% CI: 3.682-15.115;
      P<.001) were independent predictors of favorable outcomes at 3 months.
      CONCLUSIONS: Women are twice as likely to have CNI from the 2- to 24-hour period
      after IV tPA. ENI and CNI within the first 24 hours are strong predictors of
      favorable functional outcomes in thrombolyzed AIS patients.

PMID- 23954602
TI  - Cerebral embolic stroke after disappearing takotsubo cardiomyopathy.
AB  - Takotsubo cardiomyopathy can induce cerebral embolic stroke because of
      intracardiac thrombosis, but the timing of cardiogenic embolism relating to
      takotsubo cardiomyopathy has not been well described. We evaluated a 71-year-old
      woman with takotsubo cardiomyopathy, who developed cardiogenic cerebral embolism
      after recovery of cardiac wall motion. Nevertheless, we treated her with
      anticoagulation therapy. The present clinical observation suggests that attention
      should be paid to the timing when takotsubo cardiomyopathy resolves against risk
      of cardiogenic cerebral embolism. 

PMID- 23954604
TI  - Stroke chameleons.
AB  - BACKGROUND: Many conditions called "stroke mimics" may resemble acute stroke. The
      converse of the "stroke mimic" is a presentation suggestive of another condition,
      which actually represents stroke. These would be "stroke chameleons." The
      recognition of a chameleon as stroke has implications for therapy and quality of
      care. METHODS: We performed a retrospective chart review, including all cases for
      1 year in which patients had a stroke missed on hospital presentation. Initial
      erroneous diagnoses were compared for all patients correctly admitted with those
      diagnoses to determine positive predictive value (PPV) for each chameleon.
      RESULTS: Ninety-four cases were identified as chameleons where brain imaging
      revealed acute stroke. The common chameleons were initially diagnosed as altered
      mental status (AMS) (29, 31%), syncope (15, 16%), hypertensive emergency (12,
      13%), systemic infection (10, 11%), and suspected acute coronary syndrome (ACS)
      (9, 10%). The total number of patients who were diagnosed with these conditions
      over the same year were AMS (393), syncope (326), hypertensive emergency (144),
      systemic infection (753), and suspected ACS (817) (total N = 2528). For each
      chameleon diagnosis, the PPV of each presentation for acute stroke was AMS (7%),
      syncope (4%), hypertensive emergency (8%), systemic infection (1%), and suspected
      ACS (1%). CONCLUSIONS: Stroke chameleons may result in patients not receiving
      appropriate care. The largest proportions of chameleons were AMS, syncope,
      hypertensive emergency, systemic infection, and suspected ACS. Patients diagnosed
      with hypertensive emergency or AMS had an 8% and 7% chance of having an acute
      stroke. Physicians should consider stroke in patients with these diagnoses with a
      lower threshold to obtain neuroimaging with subsequent appropriate management.

PMID- 23954603
TI  - Cerebral perfusion change of venous hypertension on near-infrared spectroscopy
      signals after operation for dural arteriovenous fistula.
AB  - A dural arteriovenous fistula (AVF) is an arteriovenous shunt in the dura and is
      associated with a risk of intracranial hemorrhage and neurologic deficit. The
      morbidity of this disease depends on venous hypertension, and the classification
      of this disease is based on the pattern of venous drainage. The pattern of venous
      drainage relates to the clinical features of the disease, especially to the
      probability of intracranial hemorrhage. We report 1 case of dural AVF with
      retrograde leptomeningeal venous drainage. Cerebral hemodynamics were monitored
      using near-infrared spectroscopy imaging before, during, and after the 2-stage
      operative treatment. Preoperative functional near-infrared spectroscopy (fNIRS)
      showed an increase in deoxyhemoglobin (HbR) during a motor task. After partial
      coil embolization of the shunt points (stage 1), HbR increased during the first
      half of the task and decreased later, whereas oxyhemoglobin (HbO2) decreased in
      the first half of the task and increased later. After complete embolization
      (stage 2), fNIRS showed a pattern similar to that of a normal adult. The
      patient's symptoms improved gradually, and angiography showed a reduction of the
      retrograde venous drainage and venous congestion after this 2-stage operation.
      The reduction in venous hypertension may be the underlying mechanism behind the
      changes observed with fNIRS. 

PMID- 23954605
TI  - Vitamin K antagonist-associated intracerebral hemorrhage: lessons from a
      devastating disease in the dawn of the new oral anticoagulants.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) is the most feared complication
      associated with vitamin K antagonists (VKAs). We performed a retrospective study
      on the clinicoradiologic characteristics that influence its outcome. METHODS: We
      reviewed the clinical histories and neuroimaging studies of all patients attended
      at the Hospital Universitario Central de Asturias in 2010-2011 who had an ICH
      while being on VKA and analyzed the differential characteristics between patients
      with acceptable versus poor outcomes attending to 3 end points: death, poor
      outcome (modified Rankin Scale [mRS] score >= 4) at discharge, and poor outcome 3
      months later. Additionally, CHA2DS2-VASc and HAS-BLED scores (validated tools for
      prediction of the risk of stroke and major hemorrhage, respectively, in patients
      with atrial fibrillation) were calculated to assess a priori risk-benefit balance
      for anticoagulant therapy. RESULTS: Eighty patients entered the sample (median
      age of 79 years). A priori annual risk of major bleeding surpassed ischemic
      stroke risk-without anticoagulation-only in 4. Fifty percent of the patients had
      an initial Glasgow Coma Scale (GCS) score lower than 13; in 51.3%, initial
      international normalized ratio was above their therapeutic range. Median hematoma
      size was 24.75 cc(3); relevant growth (>=33%) occurred in 29.4% of patients with
      a second computed tomography scan. On multivariable analysis, overall in-hospital
      mortality (47.5%) was related to prior antiplatelet therapy (P = .008), GCS (P =
      .001), and perilesional edema size (P = .036). Baseline mRS (P = .058) and
      National Institutes of Health Stroke Scale (NIHSS) scores (P = .008) were
      associated with poor outcome at discharge (77.5%). Initial NIHSS (P = .005) and
      glycemia (P = .038) predicted 3-month poor outcome (68.3%). VKA reversal was
      performed in almost all patients, which prevented assessment of its therapeutic
      value. CONCLUSIONS: VKA-associated ICH presents in a particularly vulnerable
      population and has a poor prognosis that may be reliably predicted by several
      clinicoradiologic features.

PMID- 23954606
TI  - Ischemic stroke in evolution: predictive value of perfusion computed tomography.
AB  - BACKGROUND: Various perfusion computed tomography (PCT) parameters have been used
      to identify tissue at risk of infarction in the setting of acute stroke. The
      purpose of this study was to examine predictive value of the PCT parameters
      commonly used in clinical practice to define ischemic penumbra. The patient
      selection criterion aimed to exclude the effect of thrombolysis from the imaging
      data. METHODS: Consecutive acute stroke patients were screened and a total of 18
      patients who initially underwent PCT and CT angiogram (CTA) on presentation but
      did not qualify to receive thrombolytic therapy were selected. The PCT images
      were postprocessed using a delay-sensitive deconvolution algorithm. All the
      patients had follow-up noncontrast CT or magnetic resonance imaging to delineate
      the extent of their infarction. The extent of lesions on PCT maps calculated from
      mean transit time (MTT), time to peak (TTP), cerebral blood flow, and cerebral
      blood volume were compared and correlated with the final infarct size. A
      collateral grading score was used to measure collateral blood supply on the CTA
      studies. RESULTS: The average size of MTT lesions was larger than infarct lesions
      (P < .05). The correlation coefficient of TTP/infarct lesions (r = .95) was
      better than MTT/infarct lesions (r = .66) (P = .004). CONCLUSIONS: A widely
      accepted threshold to define MTT lesions overestimates the ischemic penumbra. In
      this setting, TTP with appropriate threshold is a better predictor of infarct in
      acute stroke patients. The MTT/TTP mismatch correlates with the status of
      collateral blood supply to the tissue at risk of infarction.

PMID- 23954607
TI  - Hyponatremia in the prognosis of acute ischemic stroke.
AB  - BACKGROUND: Hyponatremia is a risk factor for stroke and cardiovascular disease.
      Even mild hyponatremia is associated with increased 30-day mortality after
      myocardial infarction, and it has recently shown to increase the 3-year mortality
      after a stroke. In this work, we investigated both acute and chronic clinical
      outcomes after a stroke in hyponatremic patients. METHODS: We reviewed all
      patients admitted between 2004 and 2011 with the diagnosis of acute ischemic
      stroke. Hyponatremia was defined as serum sodium level less than 135 mmol/L and
      recorded on admission. All hemorrhagic strokes were excluded. Data were analyzed
      using multivariate logistic regression. RESULTS: A total of 3585 patients with
      stroke were identified. Hyponatremia was observed in 565 (16%) patients. Baseline
      characteristics were similar between groups except heart failure (P = .015),
      cancer (P = .038), diabetes (P < .001), and dementia (P = .015). Hyponatremic
      patients had higher National Institutes of Health Stroke Scale (NIHSS) score on
      admission (P = .032) and at discharge (P = .02). Despite similar modified Barthel
      Index (mBI) preadmission, patients with hyponatremia had worse mBI on admission
      (P = .049). Hyponatremia was associated with higher mortality in hospital (P =
      .039) and at 3-month (P = .001) and 12-month follow-ups (P = .001). A poorer
      discharge disposition was seen in the hyponatremia group (P = .004).
      Complications during admission were similar between groups except for urinary
      infection (P = .008). Patients with hyponatremia had worse NIHSS and mBI values
      on admission, and their deficits worsened during their hospitalization.
      CONCLUSIONS: This is the first study to demonstrate that hyponatremia is
      associated with acute mortality and poorer discharge dispositions and to confirm
      that higher mortality occurs in these patients, even after 12 months after a
      stroke.

PMID- 23954608
TI  - Onset Time of Ischemic Events and Antiplatelet Therapy after Intracranial Stent
      assisted Coil Embolization.
AB  - BACKGROUND: Stent-assisted coil embolization is effective for intracranial
      aneurysms, especially wide-necked aneurysms; however, the optimal antiplatelet
      regimens for ischemic events that develop after coil embolization have not yet
      been established. We aimed to determine the onset time of such postoperative
      ischemic events and the relationship between these events and antiplatelet
      therapy. METHODS: We performed coil embolization using a vascular reconstruction
      stent for 43 cases of intracranial aneurysms and evaluated the incidence of
      postoperative ischemic events in these cases. RESULTS: Nine patients showed
      postoperative ischemic events during the follow-up period (13 +/- 7 months). Two
      patients developed cerebral infarction within 24 hours. Five patients developed
      transient ischemic attack within 40 days while they were receiving dual
      antiplatelet therapy. In addition, 1 patient showed cerebral infarction 143 days
      postoperatively during single antiplatelet therapy, and a case of transient
      visual disturbance was reported 191 days postoperatively (49 days after
      antiplatelet therapy had been discontinued). We increased the number of
      antiplatelet agents in 4 of these patients. The other 5 patients were under
      strict observation with dual antiplatelet therapy. All these patients were
      shifted to single antiplatelet therapy 3-13 months postoperatively. No recurrence
      of ischemic events was noted. CONCLUSIONS: Postoperative ischemic events are most
      likely to occur within 40 days postoperatively. For patients with postoperative
      ischemic events, additional ischemic events can be prevented by increasing the
      number of antiplatelet agents; subsequently, they can be shifted to single
      antiplatelet therapy after the risk of recurrence has decreased.

PMID- 23954610
TI  - A dilated surface appearance on basiparallel anatomic scanning-magnetic resonance
      imaging is a useful tool for the diagnosis of spontaneous vertebral artery
      dissection in lateral medullary infarction.
AB  - Spontaneous dissection of the vertebral artery (VA) is a major vascular lesion
      causing lateral medullary infarction (LMI). A dilated surface appearance of the
      VA is a feature of VA dissection and can be observed on basiparallel anatomic
      scanning (BPAS)-magnetic resonance imaging (MRI). The aim of this study was to
      validate BPAS-MRI in the diagnosis of VA dissection in patients with LMI. The
      subjects of the present study were 41 consecutive patients with LMI within 7 days
      of onset. The diagnosis of VA dissection was made with the clinical criteria
      based diagnosis. Percent (%) dilatation of the VA on BPAS-MRI was calculated by
      comparing the maximum surface diameter of the intracranial VA to the diameter of
      the distal normal surface of the VA. Fourteen patients (34%) were diagnosed with
      VA dissection. The optimal cutoff % dilatation of the VA for dissection was more
      than 169%. The sensitivity and specificity of % dilatation of VA more than 169%
      and aneurysmal dilatation, stenosis, or occlusion on magnetic resonance
      angiography (MRA) for VA dissection were 92.9% and 81.5%, respectively. BPAS-MRI
      combined with time-of-flight-MRA is a useful tool for the diagnosis of VA
      dissection in patients with acute LMI. 

PMID- 23954611
TI  - Rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial
      fibrillation in relation to the CHADS2 score: a subgroup analysis of the J-ROCKET
      AF trial.
AB  - BACKGROUND: Results from a trial of rivaroxaban versus warfarin in 1280 Japanese
      patients with atrial fibrillation (J-ROCKET AF) revealed that rivaroxaban was
      noninferior to warfarin with respect to the principal safety outcome. In this
      subanalysis, we investigated the safety and efficacy of rivaroxaban and warfarin
      in relation to patients' CHADS2 scores. RESULTS: The mean CHADS2 score was 3.25,
      and the most frequent scores were 3 and 4. No statistically significant
      interactions were observed between principal safety outcome event rates and
      CHADS2 scores with respect to treatment groups (P value for interaction = .700).
      Irrespective of stratification into moderate- and high-risk groups based on
      CHADS2 scores of 2 and 3 or more, respectively, no differences in principal
      safety outcome event rates were observed between rivaroxaban- and warfarin
      treated patients (moderate-risk group: hazard ratio [HR], 1.06; 95% confidence
      interval [CI], .58-1.95; high-risk group: HR, 1.11; 95% CI, .86-1.45; P value for
      interaction = .488). The primary efficacy end point rate in the rivaroxaban
      treated group was numerically lower than in the warfarin-treated group,
      regardless of risk group stratification (moderate-risk group: HR, .46; 95% CI,
      .09-2.37; high-risk group: HR, .49; 95% CI, .22-1.11; P value for interaction =
      .935). CONCLUSION: This subanalysis indicated that the safety and efficacy of
      rivaroxaban compared with warfarin were similar, regardless of CHADS2 score.

PMID- 23954609
TI  - Safety of protocol violations in acute stroke tPA administration.
AB  - BACKGROUND: Intravenous (IV) tissue plasminogen activator remains the only
      approved therapy for acute ischemic stroke (AIS) in the United States; however,
      less than 10% of patients receive treatment. This is partially because of the
      large number of contraindications, narrow treatment window, and physician
      reluctance to deviate from these criteria. METHODS: We retrospectively analyzed
      consecutive patients who received IV thrombolysis at our stroke center for
      National Institute of Neurological Disorders and Stroke (NINDS) protocol
      violations and rates of symptomatic intracerebral hemorrhage (sICH). Other
      outcome variables included systemic hemorrhage, modified Rankin Scale at
      discharge, and discharge disposition. RESULTS: A total of 212 patients were
      identified in our stroke registry between 2009 and 2011 and included in the
      analysis. Protocol violations occurred in 76 patients (36%). The most common
      violations were thrombolysis beyond 3 hours (26%), aggressive blood pressure
      management (15%), elevated prothrombin time (PT) or partial thromboplastin time
      (PTT) (6.6%), minor or resolving deficits (4.2%), unclear time of onset (3.9%),
      and stroke within 3 months (3%). There were no significant differences in any of
      the safety outcomes or discharge disposition between patients with or without
      protocol violations. Controlling for age, National Institutes of Health Stroke
      Scale on admission, and glucose on admission, there was no significant increase
      in sICH (odds ratio: 3.8; 95% confidence interval: .37-38.72) in the patients who
      had protocol violations. CONCLUSIONS: Despite more than one third of patients
      receiving thrombolysis with protocol violations, overall rates of hemorrhage
      remained low and did not differ from those who did not have violations. Our data
      support the need to expand access to thrombolysis in AIS patients.

PMID- 23954612
TI  - Specific needs for telestroke networks for thrombolytic therapy in Japan.
AB  - The concept of telestroke networks has been proposed to overcome regional
      disparities in stroke treatment. Such networks do not yet operate in Japan. We
      aimed to determine the specific needs for telestroke networks and to estimate the
      effects on the number of thrombolytic therapies. Five of the 47 Japanese
      prefectures with various population densities to estimate the nationwide effect
      of telestroke networks were selected. The questionnaire survey was administered
      at hospitals in these prefectures that are authorized to admit patients with
      acute stroke. Low-volume hospitals that annually treated fewer than 12 patients
      with acute stroke had never used tissue plasminogen activator (tPA). The number
      of days when telestroke support might have been needed varied depending on the
      size of the population aged 65 years or older within a 30-minute-driving-time
      area of a hospital and the annual number of patients treated within 3 hours of
      onset. The geographic information system analysis showed that .6%-8.3% of the
      population lived in areas where they could not reach a hospital for acute stroke
      treatment within 60 minutes. If 24/7 full telestroke support was introduced to
      the existing hospitals, 6.8-69.3 more patients could be treated by intravenous
      (IV) tPA annually. These numbers exceeded the estimated annual increases of .8
      13.7 more patients if a drip-and-ship telestroke network was introduced into an
      underserved area outside the 60-minute-driving-time area. This study uncovered
      that many Japanese stroke hospitals, especially low-volume facilities located in
      rural areas, do not perform IV tPA therapy in 24/7 fashion and telestroke support
      to these hospitals may be highly effective compared with the drip-and-ship
      network in an underserved area. 

PMID- 23954613
TI  - Differential time to positivity is not predictive for central line-related
      Staphylococcus aureus bloodstream infection in routine clinical care.
AB  - OBJECTIVES: Many physicians rely on differential time to positivity (DTP) when
      diagnosing catheter-related bloodstream infection (CRBSI). We evaluated whether
      DTP from routine blood cultures can predict catheter-related Staphylococcus
      aureus bloodstream infection. METHODS AND PATIENTS: From 2006 to 2011 adult
      patients with monomicrobial S. aureus bloodstream infection and matched pairs of
      central and peripheral blood cultures were prospectively followed. CRBSI was
      defined by the absence of other infective foci and recovery of S. aureus from the
      catheter tip or catheter exit-site, or local signs of infection at the catheter
      exit site. A DTP of more than two hours (cut-off) was used to define test
      positivity. RESULTS: CRBSI was present in 30 (34%, prevalence) of 87 patients. In
      24 (28%) patients a DTP of more than two hours was measured: eleven patients had
      CRBSI, ten deep-seated infections, and in three patients an infective focus was
      not identified. DTP showed a positive predictive value of 0.46 [95% confidence
      interval (CI) 0.28 to 0.65], and a negative predictive value of 0.70 [95% CI 0.58
      to 0.80]. CONCLUSION: The low test performance suggests that DTP is not useful in
      diagnosing CRBSI in routinely obtained blood cultures. Therefore, physicians
      should not solely rely on DTP and rather promote catheter removal and culture.

PMID- 23954614
TI  - Immunopathological aspects of schistosomiasis-associated pulmonary arterial
      hypertension.
AB  - OBJECTIVES: Pulmonary hypertension is a lethal complication of chronic
      hepatosplenic schistosomiasis. Little is known of the underlying (immuno
      )histopathological characteristics of lung vasculopathy. METHODS: We
      characterized vasculopathy and inflammation in lung tissue of 10 patients with
      Schistosomiasis-associated PH (SCH-PH) in comparison to 22 idiopathic pulmonary
      arterial hypertension (IPAH) patients and 10 normal controls. SCH-PH cases were
      younger than controls. RESULTS: Plexiform lesions and/or angiomatoid lesions were
      found in 10/10 SCH-PH, and 19/22 IPAH patients (chi2 p = 0.22). Lung granulomas
      with Schistosoma eggs were found in 2/10 of SCH-PH cases. PAH cases had increased
      peri-arterial density of CD3+ T cells, chymase+ and tryptase+ mast cells when
      compared to controls (p <= 0.047). SCH-PH showed increased density of CD4+ cells
      when compared to controls (p = 0.025), paralleled by an increased density of
      dendritic CD83+ cells when compared to both controls and IPAH patients (p <=
      0.022). CONCLUSION: Both SCH-PH and IPAH feature plexogenic arteriopathy and
      increased periarterial T cell and mast cell density. SCH-PH and IPAH differ only
      with respect to the density of dendritic CD83+ cells. These findings imply
      ongoing antigenic stimulation in SCH-PH, yet a pattern of pulmonary vasculopathy
      similar to IPAH, suggestive of a final common pathway in their pathogenesis of
      PAH.

PMID- 23954615
TI  - Cytokine responses to quantiferon peptides in pediatric tuberculosis: a pilot
      study.
AB  - OBJECTIVES: Detailed understanding of tuberculosis (TB) immunopathology and
      cytokine/chemokine responses can ultimately lead to the development of new
      diagnostic tools, especially useful in children where TB diagnosis remains
      challenging. METHODS: Nineteen cytokine/chemokine responses to Mycobacterium
      tuberculosis (M.tb) antigens were analyzed in 47 children distributed as follow:
      28 with TB-disease (TD), 12 with latent TB and 7 uninfected controls. All the
      cytokines and chemokines were quantified in a multiplexed microsphere-based assay
      by using residual plasma from the quantiFERON kit (IFNgamma release assay).
      RESULTS: IP-10, IL-2, IL-5 and IL-13 were among the best cytokines to diagnose
      infection as related by the area under ROC curve for IP-10 (0.96, 95%CI: 0.91
      1.00), IL-2 (0.98, 95%CI: 0.93-1.02), IL-5 (0.91, 95%CI: 0.81-1.01) and IL-13
      (0.97, 95%CI: 0.93-1.00). None of the 5 biomarkers, however, discriminated TB
      disease from latent-TB. Finally, lower IL-5 (p = 0.02) and IL-13 (p = 0.02)
      levels were observed in severe opposed to non-severe TB. CONCLUSION: These
      results suggest that IP-10, IL-2, IL-5 and IL-13 may find a diagnostic
      application in pediatric tuberculosis and argue against the paradigm of a
      negative influence of Th2 responses in severe pediatric M.tb infection.

PMID- 23954616
TI  - Purification, recovery, and characterization of chick pea (Cicer arietinum) beta
      galactosidase in single step by three phase partitioning as a rapid and easy
      technique.
AB  - In this study chick pea beta-galactosidase was first time purified and recovered
      in single step by three phase partitioning (TPP). Optimal purification parameters
      for TPP were 60% ammonium sulfate saturation (w/v) with 1:0.5 (v/v) ratio of
      crude extract:t-butanol at pH 6.8, which gave 10.1 purification fold with 133%
      recovery of beta-galactosidase. SDS-PAGE analysis showed that protein has two
      subunits with molecular masses of 48 and 38kDa, respectively. Characterization of
      enzyme showed that optimal pH of purified enzyme was 2.8 and optimal temperature
      was 50 degrees C. Enzyme was further characterized by the Arrhenius activation
      energy and Michael-Menten kinetic constants. Activation energy (Ea) was
      calculated by using Arrhenius equation and determined to be 15.52kcalmol(-1). Km
      value of purified enzyme was estimated for the o-nitrophenyl beta-d
      galactopyranoside (ONPG) substrate as 1.09mM, while its maximum velocity, Vm was
      0.90U/mL/min at 37 degrees C. TPP improved substrate affinity of enzyme by the
      increased flexibility during the partitioning. TPP is simple, easy and economic
      technique for purification and recovery of beta-galactosidase from chick pea, and
      has a big potential use for industrial applications. 

PMID- 23954617
TI  - 12q21 Microdeletion in a fetus with Meckel syndrome involving CEP290/MKS4.
AB  - We report on a fetus with Meckel syndrome diagnosed during the 21st gestational
      week, hydrocephalus and bilateral hyperechogenic kidneys were then detected on
      ultrasonography. Fetal pathological examination showed facial dysmorphism,
      occipital meningoencephalocele, characteristic renal cysts, mild hepatic ductal
      dysplasia, hydrocephalus in association with extreme cerebellar vermis hypoplasia
      and brainstem anomalies. Molecular and cytogenetic analysis identified a
      paternally inherited CEP290/MKS4 (MIM611134) (12q21) nonsense mutation and a
      maternal 12q21 microdeletion. Two cases with such a mechanism have previously
      been described in the literature, one of them involves an inherited
      microdeletion. The observation of such cases highlights the existence of a
      pathogenic mechanism which involves deletion and point mutation, and illustrates
      how homozygosity can hide hemizygosity when usual sequencing methods are used.
      The identification of hemizygosity enables to determine precisely the molecular
      mechanism and to understand some phenotypic variations. As they act as complete
      loss of function allele, deletions might give indication on the severity of the
      associated point mutation. This clinical report highlights the importance of
      fetal pathology following termination of pregnancies in order to guide molecular
      analysis and the potential role of cytogenetic cryptic disorders in autosomal
      recessive disease. The use of polymorphic marker analysis in association with
      FISH or arrayCGH provided an accurate identification of molecular mechanisms,
      accurate genetic counseling and optimized strategy for next pregnancies or
      preimplantation diagnosis. 

PMID- 23954618
TI  - Role of novel DSP_p.Q986X genetic variation in arrhythmogenic right ventricular
      cardiomyopathy.
AB  - INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy is an inherited
      disease characterized by a progressive myocardium fibrofatty replacement. This
      abnormality disrupts electrical transmission causing ventricular arrhythmias and
      sudden cardiac death. This genetic disease is transmitted mainly with an
      autosomal dominant pattern. Our aim was to identify the genetic defect
      responsible for the pathology in a Spanish family, and to perform its phenotype
      connotations. MATERIAL AND METHODS: A total of 15 individuals in a three
      generation Spanish family were screened after the sudden cardiac death of one
      family member. All they underwent a complete physical examination, 12-lead
      electrocardiogram, 2-dimensional echocardiography, magnetic resonance imaging,
      exercise stress test, 24-h Holter and genetic testing. RESULTS: Autopsy revealed
      the presence of biventricular arrhythmogenic dysplasia in deceased member. Six
      family members showed clinical symptoms but only three of them fulfilled definite
      diagnostic criteria of the disease. Genetic analysis showed a novel nonsense
      genetic variation in nine family members. All family members with clinical
      symptoms carried the genetic variation. CONCLUSIONS: Genetic testing in families
      affected by arrhythmogenic right ventricular cardiomyopathy helps to identify the
      genetic cause responsible for the disease. The incomplete penetrance and variable
      phenotypic expression highlights the need of comprehensive genetic analysis and
      further phenotype implications of genetics to clarify the pathophysiology of the
      disease.

PMID- 23954619
TI  - Possible mechanism of structural transformations induced by StAsp-PSI in lipid
      membranes.
AB  - In the present work we have analyzed the effect of StAsp-PSI (plant-specific
      insert of potato aspartic protease) on the structural and thermotropic properties
      of the major phospholipid types of bacterial and animal cells. Results obtained
      suggest that StAsp-PSI induces a destabilization of the membrane bilayers,
      depending on the time of interaction between the protein and the bilayers, rather
      than on its concentration. This temporal delay would be consistent with a lateral
      diffusion of StAsp-PSI monomers to assemble into aggregates to form pores. Like
      with the results previously reported for the StAsp-PSI circular dichroism, data
      obtained here from IR spectroscopy show that there are slight changes in the
      StAsp-PSI secondary structure in the presence of lipid membranes; suggesting that
      these changes could be related with the StAsp-PSI self-association. Results
      obtained from steady-state fluorescence anisotropy and differential scanning
      calorimetry assays suggest that StAsp-PSI interacts with both uncharged and
      negatively charged phospholipids, modulates the phase polymorphic behavior of
      model membranes and partitions and buries differentially in the membrane
      depending on the presence of negatively charged phospholipids. 

PMID- 23954620
TI  - Alteration of plasma phospholipid fatty acid profile in patients with septic
      shock.
AB  - In septic shock patients, alterations of plasma phospholipid fatty acid profile
      have never been described. The purpose of this monocentric, non-interventional,
      observational prospective study was to describe this fatty acid profile in the
      early phase of septic shock in intensive care unit. Thirty-seven adult patients
      with septic shock were included after the first day of stay in intensive care
      unit, before any form of artificial nutritional support. Plasma phospholipid
      fatty acid composition was determined by gas chromatography. All biological data
      from patients with septic shock were compared with laboratory reference values.
      Patients presented hypocholesterolemia and hypertriglyceridemia. They had low
      concentrations of phospholipid fatty acids specifically n-6 and n-3
      polyunsaturated fatty acids (PUFAs) with a high n-6/n-3 ratio. Plasma
      phospholipid PUFA concentrations were strongly correlated with cholesterolemia.
      PUFAs/SFAs (saturated fatty acids) and PUFAs/MUFAs (monounsaturated fatty acids)
      ratios were low because of low percentage of n-6 and n-3 PUFAs and high
      percentage of SFAs and MUFAs. Low levels of plasma long chain PUFAs (>=20
      carbons) were significantly associated with mortality at 28th day. In conclusion,
      plasma phospholipid FA profile of septic patients is very characteristic, close
      to that of acute respiratory distress syndrome and mortality is associated with
      long chain PUFA decrease. This profile could be explained by numerous non
      exclusive physio-pathological processes 1) an activation of hepatic de novo
      lipogenesis that could contribute to hepatic steatosis, 2) an elevated adipose
      tissue lipolysis, 3) an increased free radical attack of FA by oxidative stress,
      4) an over-production of inflammatory lipid mediators.

PMID- 23954621
TI  - Purification and characterisation of recombinant Bacteroides fragilis toxin-2.
AB  - Fragilysin (BFT) is metalloprotease that is secreted by enterotoxigenic
      Bacteroides fragilis. Studying the mechanism of BFT interaction with intestinal
      epithelial cells requires a pure protein sample. In this study, we cloned DNA
      fragments coding for the catalytic domain of fragilysin-2 and profragilysin-2
      into an E. coli expression vector. Purification methods for the recombinant
      fragilysin-2 catalytic domain and profragilysin-2 were developed. In addition, we
      obtained mature active fragilysin-2 from recombinant proprotein by limited
      tryptic digestion. We tested the biological activity of the recombinant protein
      samples and revealed that E-cadherin was cleaved when HT-29 cells were treated
      with mature fragilysin-2 but not with profragilysin-2. Azocoll, azocasein and
      gelatin were not proteolytically cleaved by mature fragilysin-2. Proteins
      released in culture medium after HT-29 cells treatment with mature active BFT-2
      were identified.

PMID- 23954622
TI  - Associations of particulate air pollution and daily mortality in 16 Chinese
      cities: an improved effect estimate after accounting for the indoor exposure to
      particles of outdoor origin.
AB  - People typically spend most of their time indoors. We modeled the daily indoor
      PM10 concentrations of outdoor origin using a set of exposure parameters,
      including the fraction of residences with air conditionings (AC), the fraction of
      time that windows are closed when cooling occurs for buildings with AC, the
      fractions of time that windows are open or closed for buildings with or without
      AC, the particle penetration factors, air change rates, and surface removal rate
      constant of PM10. We calculated the time-weighted average of the simulated indoor
      PM10 concentration of outdoor origin and the original recorded outdoor PM10
      concentration. We then evaluated the acute effects of PM10 using traditional and
      amended exposure metrics in 16 Chinese cities. Compared with the original
      estimates, the new effect estimates almost doubled, with improved model fit and
      attenuated between-city heterogeneity. Conclusively, this proposed exposure
      assessment approach could improve the effect estimates of ambient particles. 

PMID- 23954623
TI  - Atmospheric polychlorinated biphenyls in Indian cities: levels, emission sources
      and toxicity equivalents.
AB  - Atmospheric concentration of Polychlorinated biphenyls (PCBs) were measured on
      diurnal basis by active air sampling during Dec 2006 to Feb 2007 in seven major
      cities from the northern (New Delhi and Agra), eastern (Kolkata), western (Mumbai
      and Goa) and southern (Chennai and Bangalore) parts of India. Average
      concentration of Sigma25PCBs in the Indian atmosphere was 4460 (+/- 2200) pg/m(
      3) with a dominance of congeners with 4-7 chlorine atoms. Model results (HYSPLIT,
      FLEXPART) indicate that the source areas are likely confined to local or regional
      proximity. Results from the FLEXPART model show that existing emission
      inventories cannot explain the high concentrations observed for PCB-28.
      Electronic waste, ship breaking activities and dumped solid waste are attributed
      as the possible sources of PCBs in India. Sigma25PCB concentrations for each city
      showed significant linear correlation with Toxicity equivalence (TEQ) and
      Neurotoxic equivalence (NEQ) values.

PMID- 23954624
TI  - Strand-specific RNA sequencing uncovers chloroplast ribonuclease functions.
AB  - Organellar gene expression incorporates ribonucleases as indispensable
      participants. Here, we explored the capacity of strand-specific RNA sequencing
      (RNA-Seq) as a tool to analyze chloroplast ribonuclease functions using the 3'
      >5' exoribonuclease polynucleotide phosphorylase (PNPase) as a proof of concept.
      The role of PNPase in transcript 3' end maturation was easily monitored, and
      additional targeted mRNAs were discovered. Moreover, a role in tRNA precursor
      degradation was predicted and validated. These results, together with previously
      published data, suggest that RNA-Seq represents a unique opportunity to decipher
      the roles of organellar ribonucleases and deepen our understanding of chloroplast
      gene expression. 

PMID- 23954625
TI  - Concerted action of activation-induced cytidine deaminase and uracil-DNA
      glycosylase reduces covalently closed circular DNA of duck hepatitis B virus.
AB  - Covalently closed circular DNA (cccDNA) forms a template for the replication of
      hepatitis B virus (HBV) and duck HBV (DHBV). Recent studies suggest that
      activation-induced cytidine deaminase (AID) functions in innate immunity,
      although its molecular mechanism of action remains unclear, particularly
      regarding HBV restriction. Here we demonstrated that overexpression of chicken
      AID caused hypermutation and reduction of DHBV cccDNA levels. Inhibition of
      uracil-DNA glycosylase (UNG) by UNG inhibitor protein (UGI) abolished AID-induced
      cccDNA reduction, suggesting that the AID/UNG pathway triggers the degradation of
      cccDNA via cytosine deamination and uracil excision. 

PMID- 23954626
TI  - Extracellular alpha-synuclein induces calpain-dependent overactivation of cyclin
      dependent kinase 5 in vitro.
AB  - Extracellular alpha-synuclein (ASN) could be involved in the pathomechanism of
      Parkinson's disease (PD) via disturbances of calcium homeostasis, activation of
      nitric oxide synthase and oxidative/nitrosative stress. In this study we analyzed
      the role of cyclin-dependent kinase 5 (Cdk5) in the molecular mechanism(s) of ASN
      toxicity. We found that exposure of PC12 cells to ASN increases Cdk5 activity via
      calpain-dependent p25 formation and by enhancement of Cdk5 phosphorylation at
      Tyr15. Cdk5 and calpain inhibitors prevented ASN-evoked cell death. Our findings,
      indicating the participation of Cdk5 in ASN toxicity, provide new insight into
      how extracellular ASN may trigger dopaminergic cell dysfunction in PD. 

PMID- 23954627
TI  - A western blot assay to measure cyclin dependent kinase activity in cells or in
      vitro without the use of radioisotopes.
AB  - We developed a quantitative method to measure the activity of cyclin-dependent
      kinases (Cdks) by western blotting, without radioisotopes. We prepared a
      recombinant protein substrate based upon the natural Cdk1 substrate, PP1Calpha.
      By combining this substrate in a western blot method using fluorochrome based
      antibodies and phospho-imager analysis, we measured the Km of ATP binding to Cdk1
      to be 3.5 MUM. We then measured Cdk1 activity in cell extracts from interphase or
      mitotic cells, and demonstrated that previously identified Cdk inhibitors could
      be detected by this assay. Our data show that we have a safe, reliable assay to
      identify Cdk1 inhibitors and measure Cdk1 activity.

PMID- 23954628
TI  - PEGylated polylysine dendrimers increase lymphatic exposure to doxorubicin when
      compared to PEGylated liposomal and solution formulations of doxorubicin.
AB  - Improved delivery of chemotherapeutic drugs to the lymphatic system has the
      potential to augment outcomes for cancer therapy by enhancing activity against
      lymph node metastases. Uptake of small molecule chemotherapeutics into the
      lymphatic system, however, is limited. Nano-sized drug carriers have the
      potential to promote access to the lymphatics, but to this point, this has not
      been examined in detail. The current study therefore evaluated the lymphatic
      exposure of doxorubicin after subcutaneous and intravenous administration as a
      simple solution formulation or when formulated as a doxorubicin loaded PEGylated
      poly-lysine dendrimer (hydrodynamic diameter 12 nm), a PEGylated liposome (100
      nm) and various pluronic micellar formulations (~5 nm) to thoracic lymph duct
      cannulated rats. Plasma and lymph pharmacokinetics were analysed by compartmental
      pharmacokinetic modelling in S-ADAPT, and Berkeley Madonna software was used to
      predict the lymphatic exposure of doxorubicin over an extended period of time.
      The micelle formulations displayed poor in vivo stability, resulting in
      doxorubicin profiles that were similar to that observed after administration of
      the doxorubicin solution formulation. In contrast, the dendrimer formulation
      significantly increased the recovery of doxorubicin in the thoracic lymph after
      both intravenous and subcutaneous dosing when compared to the solution or
      micellar formulation. Dendrimer-doxorubicin also resulted in increases in
      lymphatic doxorubicin concentrations when compared to the liposome formulation,
      although liposomal doxorubicin did increase lymphatic transport when compared to
      the solution formulation. Specifically, the dendrimer formulation increased the
      recovery of doxorubicin in the lymph up to 30 h post dose by up to 685 fold and
      3.7 fold when compared to the solution and liposomal formulations respectively.
      Using the compartmental model to predict lymphatic exposure to longer time
      periods suggested that doxorubicin exposure to the lymphatic system would
      ultimately be 9796 times and 6.1 times greater after administration of dendrimer
      doxorubicin when compared to the solution and liposome formulations respectively.
      The recovery of doxorubicin in the sentinel lymph nodes draining the subcutaneous
      injection site was also quantified directly, and consistent with the lymph
      pharmacokinetic data, lymph node recovery was greatest for the dendrimer
      formulation (12% of dosed doxorubicin/g node) when compared to the liposome
      (1.4%/g node) and solution (<1%/g node) formulations. The data suggest that
      dendrimer-based drug delivery systems have the potential to enhance drug exposure
      to lymph-based drug targets such as lymphatic metastases.

PMID- 23954629
TI  - Location of molecules in layer-by-layer assembled microcapsules influences
      activity, cell delivery and susceptibility to enzyme degradation.
AB  - Layer-by-layer assembled microcapsules have the potential to be versatile cell
      delivery systems incorporating multiple activities and functions. However, it is
      necessary to determine the influence that different capsule locations have on
      activity of bioactive molecules in order to optimise delivery and for generation
      of multifunctional capsules. In this study we examine the influence that locating
      the bioluminescent enzyme luciferase in different microcapsule locations has on
      activity in intact synthetic and biodegradable microcapsules before and after
      cell delivery as well as its susceptibility to protease degradation. We also
      examine the effect of microcapsule position on cell transfection with plasmid
      DNA. Based on the findings of experiments in this study we also demonstrate co
      delivery of luciferase protein and plasmid DNA encoding a fluorescent protein
      from two different locations within the same microcapsule. Our studies confirm
      that, the core, subouter layer, and outer layer are optimal for cell delivery but
      these positions offer least protection from protease activity. By contrast middle
      layer molecules remain entangled with capsule layers preventing their release
      which is inefficient for cell delivery but this provides better protection from
      protease degradation. The findings of this study will enable more rationale layer
      by-layer assembly of microcapsules containing biologically active molecules for
      cell delivery and aid in the generation of multifunctional microcapsules. 

PMID- 23954630
TI  - PEGylation of HPMA-based block copolymers enhances tumor accumulation in vivo: a
      quantitative study using radiolabeling and positron emission tomography.
AB  - This paper reports the body distribution of block copolymers (made by controlled
      radical polymerization) with N-(2-hydroxypropyl)methacrylamide (HPMA) as
      hydrophilic block and lauryl methacrylate (LMA) as hydrophobic block. They form
      micellar aggregates in aqueous solution. For this study the
      hydrophilic/hydrophobic balance was varied by incorporation of differing amounts
      of poly(ethylene glycol) (PEG) side chains into the hydrophilic block, while
      keeping the degree of polymerization of both blocks constant. PEGylation reduced
      the size of the micellar aggregates (Rh=113 to 38 nm) and led to a minimum size
      of 7% PEG side chains. Polymers were labeled with the positron emitter (18)F,
      which enables to monitor their biodistribution pattern for up to 4h with high
      spatial resolution. These block copolymers were investigated in Sprague-Dawley
      rats bearing the Walker 256 mammary carcinoma in vivo. Organ/tumor uptake was
      quantified by ex vivo biodistribution as well as small animal positron emission
      tomography (PET). All polymers showed renal clearance with time. Their uptake in
      liver and spleen decreased with size of the aggregates. This made PEGylated
      polymers--which form smaller aggregates--attractive as they show a higher blood
      pool concentration. Within the studied polymers, the block copolymer of 7%
      PEGylation exhibited the most favorable organ distribution pattern, showing
      highest blood-circulation level as well as lowest hepatic and splenic uptake.
      Most remarkably, the in vivo results revealed a continuous increase in tumor
      accumulation with PEGylation (independent of the blood pool concentration)-
      starting from lowest tumor uptake for the pure block copolymer to highest
      enrichment with 11% PEG side chains. These findings emphasize the need for
      reliable (non-invasive) in vivo techniques revealing overall polymer distribution
      and helping to identify drug carrier systems for efficient therapy.

PMID- 23954631
TI  - Study of a tri-trophic prey-dependent food chain model of interacting
      populations.
AB  - The current paper accounts for the influence of intra-specific competition among
      predators in a prey dependent tri-trophic food chain model of interacting
      populations. We offer a detailed mathematical analysis of the proposed food chain
      model to illustrate some of the significant results that has arisen from the
      interplay of deterministic ecological phenomena and processes. Biologically
      feasible equilibria of the system are observed and the behaviours of the system
      around each of them are described. In particular, persistence, stability (local
      and global) and bifurcation (saddle-node, transcritical, Hopf-Andronov) analysis
      of this model are obtained. Relevant results from previous well known food chain
      models are compared with the current findings. Global stability analysis is also
      carried out by constructing appropriate Lyapunov functions. Numerical simulations
      show that the present system is capable enough to produce chaotic dynamics when
      the rate of self-interaction is very low. On the other hand such chaotic
      behaviour disappears for a certain value of the rate of self interaction. In
      addition, numerical simulations with experimented parameters values confirm the
      analytical results and shows that intra-specific competitions bears a potential
      role in controlling the chaotic dynamics of the system; and thus the role of self
      interactions in food chain model is illustrated first time. Finally, a discussion
      of the ecological applications of the analytical and numerical findings concludes
      the paper. 

PMID- 23954632
TI  - PGC-1-related coactivator (PRC) negatively regulates endothelial adhesion of
      monocytes via inhibition of NF kappaB activity.
AB  - PGC-1-related coactivator (PRC) is a growth-regulated transcriptional cofactor
      known to activate many of the nuclear genes specifying mitochondrial respiratory
      function. Endothelial dysfunction is a prominent feature found in many
      inflammatory diseases. Adhesion molecules, such as VCAM-1, mediate the attachment
      of monocytes to endothelial cells, thereby playing an important role in
      endothelial inflammation. The effects of PRC in regards to endothelial
      inflammation remain unknown. In this study, our findings show that PRC can be
      inhibited by the inflammatory cytokine LPS in cultured human umbilical vein
      endothelial cells (HUVECs). In the presence of LPS, the expression of endothelial
      cell adhesion molecular, such as VCAM1 and E-selectin, is found to be increased.
      These effects can be negated by overexpression of PRC. Importantly, monocyte
      adhesion to endothelial cells caused by LPS is significantly attenuated by PRC.
      In addition, overexpression of PRC protects mitochondrial metabolic function and
      suppresses the rate of glycolysis against LPS. It is also found that
      overexpression of PRC decreases the transcriptional activity of NF-kappaB. These
      findings suggest that PRC is a negative regulator of endothelial inflammation.

PMID- 23954633
TI  - Identification of miR-106b-93 as a negative regulator of brown adipocyte
      differentiation.
AB  - microRNAs (miRNAs) have been reported to play an essential role in the regulation
      of brown adipocyte adipogenesis. In the present study, we investigated the role
      of the miR-106b-93 cluster in the differentiation of brown adipocytes. We found
      that knockdown of miR-106b and miR-93 significantly induced the expression of
      brown fat-specific genes and promoted the accumulation of lipid-droplet in
      differentiating brown adipocytes. In addition, ectopic expression of miR-106b and
      miR-93 suppressed the mRNA level of Ucp1, a selective hallmark of brown
      adipocytes. Furthermore, the expression levels of miR-106b and miR-93 are higher
      in brown adipose tissues of high fat diet-induced obese mice compared to control
      mice. Taken together, our results identify miR-106b and miR-93 as negative
      regulators of brown adipocyte differentiation and the miR-106b-93 cluster may
      play an important role in regulating energy homeostasis. 

PMID- 23954634
TI  - Influenza A virus (H1N1) increases airway epithelial cell secretion by up
      regulation of potassium channel KCNN4.
AB  - Influenza infects the epithelial cells lining the airways. Normally epithelial
      cells move solutes through ion channels to create the osmotic drive to hydrate
      the airways. Viral alteration of this process could explain, in part, the fluid
      imbalance in the lungs and the resulting pulmonary edema that occurs during
      severe influenza infections. Using western blot and RT-qPCR, we measured ion
      channel and cytokine expression in the Calu3 airway cell line after infection
      with influenza virus (H1N1) for 48 h. We simultaneously measured chloride and
      potassium channel function by means of a short-circuit current (I(sc)) produced
      in an Ussing chamber. At a multiplicity of infection (MOI) of 10, viral M1
      protein and pro-inflammatory cytokine expression was observed 24h post-infection,
      despite a lack of measurable change in Isc. However, we observed a decreased
      secretory response in cAMP- and calcium-induced Isc 48 h post-infection. This
      correlated with a decrease in CFTR and KCNN4 protein levels. Interestingly, a
      viral dose of an MOI 0.6 revealed an increased secretory response that correlated
      with pro-inflammatory cytokine expression. This increased secretory response
      seemed to be primarily driven through KCNN4. We detected an increase in KCNN4
      mRNA and protein, while CFTR function and expression remained unchanged.
      Furthermore, inhibition of the KCNN4-stimulated I(sc) with TRAM-34, a specific
      inhibitor, ameliorated the response, implicating KCNN4 as the main driving force
      behind the secretory phenotype.

PMID- 23954635
TI  - The crystal structure of D-mandelate dehydrogenase reveals its distinct substrate
      and coenzyme recognition mechanisms from those of 2-ketopantoate reductase.
AB  - D-Mandelate dehydrogenases (D-ManDHs), belonging to a new d-2-hydroxyacid
      dehydrogenase family, catalyze the conversion between benzoylformate and d
      mandelate using NAD as a coenzyme. We determined the first D-ManDH structure,
      that of ManDH2 from Enterococcus faecalis IAM10071. The overall structure showed
      ManDH2 has a similar fold to 2-ketopantoate reductase (KPR), which catalyzes the
      conversion of 2-ketopantoate to d-pantoate using NADP as a coenzyme. They share
      conserved catalytic residues, indicating ManDH2 has the same reaction mechanism
      as KPR. However, ManDH2 exhibits significant structural variations in the
      coenzyme and substrate binding sites compared to KPR. These structural
      observations could explain their different coenzyme and substrate specificities.

PMID- 23954636
TI  - Zebrafish ghrelin is expressed in pancreatic endocrine cells and regulated by
      metabolic state.
AB  - Mammalian ghrelin is a stomach-derived peptide that stimulates secretion of
      growth hormone and food intake. Zebrafish is an excellent model system for
      forward genetic studies, and many aspects of energy homeostasis characterized in
      mammals appear to be conserved in the zebrafish. In this study, we investigated
      the expression and regulation of zebrafish ghrelin by metabolic status.
      Quantitative RT-PCR revealed that zebrafish ghrelin is highly enriched in
      anterior gut associated tissues. Using in situ hybridization with adult zebrafish
      tissues, we found that zebrafish ghrelin mRNA was not expressed in intestine
      tissue, but rather in clusters of endocrine pancreas cells distinct from insulin
      expressing islets. Fasting specifically upregulated pancreatic ghrelin but not
      brain ghrelin expression by 3- to 4-fold and refeeding restored ghrelin
      transcript to control levels seen in the fed group within 5 h. These results
      demonstrate that although ghrelin is expressed in a different site in zebrafish,
      it is responsive to metabolic state in a similar manner as mammalian ghrelin,
      suggesting a role in the regulation of feeding in teleosts, and thus validate the
      utility of zebrafish as a genetic model system for the analysis of the ghrelin
      system and energy homeostasis.

PMID- 23954637
TI  - POT1b regulates phagocytosis and NO production by modulating activity of the
      small GTPase Rab5.
AB  - The protection of telomeres 1 (POT1) protein is a 75-kDa protein that plays an
      important role in telomere protection, which is related to telomere elongation.
      Although POT1 is present in and acts in the nuclei, little is known about the
      functions of POT1 in the cytosol. We here examined the role of POT1b in
      phagocytosis in a macrophage-like RAW 264 cell line. We found that POT1 was
      present in the cytosol, where it was bound to Rab5, which is a protein important
      for endocytosis. POT1b knockdown in RAW 264 cells increased Rab5 activity and
      facilitated the phagocytosis of whole cells of Escherichia coli and
      Staphylococcus aureus. Furthermore, POT1b knockdown enhanced the expression of
      inducible nitric oxide synthase (iNOS), followed by the promotion of nitric oxide
      (NO) generation in response to stimulation by bacterial whole cells. These
      results suggest that POT1b negatively regulates phagocytosis by controlling Rab5
      activity and thereby modulates bacteria-induced NO generation. These findings
      suggest that POT1b participates in innate immune responses. 

PMID- 23954638
TI  - Small proline-rich protein-1B is overexpressed in human oral squamous cell cancer
      stem-like cells and is related to their growth through activation of MAP kinase
      signal.
AB  - Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are considered to be
      essential for tumor maintenance, recurrence and metastasis. Therefore,
      eradication of CSCs/CICs is essential to cure cancers. However, the molecular
      mechanisms of CSCs/CICs are still elusive. In this study, we investigated the
      molecular mechanism of the cell growth of oral CSCs/CICs. Oral CSCs/CICs were
      isolated as aldehyde dehydrogenase 1 bright (ALDH1(br)) cells by the ALDEFLUOR
      assay. Small proline-rich protein-1B (SPRR1B) gene was shown to be overexpressed
      in ALDH1(br) cells by a cDNA microarray and RT-PCR. SPRR1B was shown to have a
      role in cell growth and maintenance of ALDH1(br) cells by SPRR1B overexpression
      and knockdown experiments. To elucidate the molecular mechanism by which SPRR1B
      regulates cell growth, further cDNA microarray analysis was performed using
      SPRR1B-overexpressed cells and cells with SPRR1B knocked down by siRNA.
      Expression of the tumor suppressor gene Ras association domain family member 4
      (RASSF4) was found to be suppressed in SPRR1B-overexpressed cells. On the other
      hand, the expression of RASSF4 was enhanced in cells in which SPRR1B expression
      was knocked down by SPRR1B-specific siRNA. RASSF4 has an RA (Ras association)
      domain, and we thus hypothesized that RASSF4 modulates the MAP kinase signal
      downstream of the Ras signal. MAP kinase signal was activated in SPRR1B
      overexpressed cells, whereas the signal was suppressed in SPRR1B knocked down
      cells. Taken together, the results indicate that the expression of SPRR1B is
      upregulated in oral CSCs/CICs and that SPRR1B has a role in cell growth by
      suppression of RASSF4.

PMID- 23954640
TI  - Fibrosis and adipose tissue dysfunction.
AB  - Fibrosis is increasingly appreciated as a major player in adipose tissue
      dysfunction. In rapidly expanding adipose tissue, pervasive hypoxia leads to an
      induction of HIF1alpha that in turn leads to a potent profibrotic transcriptional
      program. The pathophysiological impact of adipose tissue fibrosis is likely to
      play an equally important role on systemic metabolic alterations as fibrotic
      conditions play in the liver, heart, and kidney. Here, we discuss recent advances
      in our understanding of the genesis, modulation, and systemic impact of excessive
      extracellular matrix (ECM) accumulation in adipose tissue of both rodents and
      humans and the ensuing impact on metabolic dysfunction. 

PMID- 23954641
TI  - Novel endoscopic therapeutics for early gastric cancer.
AB  - Gastrointestinal cancers are among the commonest cancers worldwide. Treatment of
      these cancers at an early stage will result in a significantly better prognosis.
      Endoscopic submucosal dissection (ESD) is a new method of endoscopic resection
      that can achieve higher rates of en bloc resection for early gastrointestinal
      neoplasia. Three retrospective case-control studies showed that ESD achieved
      significantly higher en bloc resection with lower recurrence rates than
      endoscopic mucosal resection for treatment of early gastric cancers. Most of the
      reports on clinical outcomes of ESD were from countries with a high incidence of
      gastric cancers, including Japan and Korea. The development of ESD has been slow
      for countries outside Japan and Korea because ESD requires a high level of
      endoscopic skills, and the dissection was performed single-handedly without
      assistance. A newly developed robotic endoscopic platform will enhance the
      performance of ESD through the use of 2 robotic arms: one arm for retraction of
      the mucosa and the other arm for dissection. 

PMID- 23954639
TI  - Metabolic regulation by p53 family members.
AB  - The function of p53 is best understood in response to genotoxic stress, but
      increasing evidence suggests that p53 also plays a key role in the regulation of
      metabolic homeostasis. p53 and its family members directly influence various
      metabolic pathways, enabling cells to respond to metabolic stress. These
      functions are likely to be important for restraining the development of cancer
      but could also have a profound effect on the development of metabolic diseases,
      including diabetes. A better understanding of the metabolic functions of p53
      family members may aid in the identification of therapeutic targets and reveal
      novel uses for p53-modulating drugs. 

PMID- 23954642
TI  - An unusual malformation predisposing to liver tumors.

PMID- 23954644
TI  - Insulin resistance, obesity, and liver cancer.

PMID- 23954645
TI  - Reply: To PMID 23313840.

PMID- 23954643
TI  - Liver stiffness is associated with risk of decompensation, liver cancer, and
      death in patients with chronic liver diseases: a systematic review and meta
      analysis.
AB  - BACKGROUND & AIMS: Liver stiffness measurement (LSM), using elastography, can
      independently predict outcomes of patients with chronic liver diseases (CLDs).
      However, there is much variation in reporting and consistency of findings. We
      performed a systematic review and meta-analysis to evaluate the association
      between LSM and outcomes of patients with CLDs. METHODS: We performed a
      systematic review of the literature, through February 2013, for studies that
      followed up patients with CLDs prospectively for at least 6 months and reported
      the association between baseline LSM and subsequent development of decompensated
      cirrhosis or hepatocellular carcinoma (HCC), as well as mortality. Summary
      relative risk (RR) estimates per unit of LSM and 95% confidence intervals (CIs)
      were estimated using the random effects model. RESULTS: Our final analysis
      included 17 studies, reporting on 7058 patients with CLDs. Baseline LSM was
      associated significantly with risk of hepatic decompensation (6 studies; RR,
      1.07; 95% CI, 1.03-1.11), HCC (9 studies; RR, 1.11; 95% CI, 1.05-1.18), death (5
      studies; RR, 1.22; 95% CI, 1.05-1.43), or a composite of these outcomes (7
      studies; RR, 1.32; 95% CI, 1.16-1.51). We observed considerable heterogeneity
      among studies-primarily in the magnitude of effect, rather than the direction of
      effect. This heterogeneity could not be explained by variations in study
      locations, etiologies and stages of CLD, techniques to measure liver stiffness,
      adjustment for covariates, or method of imputing relationship in the meta
      analysis. CONCLUSIONS: Based on a meta-analysis of cohort studies, the degree of
      liver stiffness is associated with risk of decompensated cirrhosis, HCC, and
      death in patients with CLDs. LSM therefore might be used in risk stratification.

PMID- 23954646
TI  - The end of prophylactic pancreatic duct stents? Proceed with caution and courage.

PMID- 23954647
TI  - Patient factors that affect quality of colonoscopy preparation.
AB  - BACKGROUND & AIMS: Optimal colonoscopy preparation requires patients to adhere to
      written instructions and be activated to complete the task. Among patients with
      chronic disease, health literacy and patient activation have been associated with
      outcome, but these factors have not been studied for colonoscopy. We examined the
      association between health literacy, patient activation, and quality of bowel
      preparation. METHODS: We analyzed outpatient colonoscopy results from 462 adults,
      55-74 years old (mean, 62 +/- 6 years), who previously completed extensive
      neurocognitive assessments as part of a prospective study (Health Literacy and
      Cognitive Function in Older Adults). We collected information on cecal
      intubation, polyp detection, bowel preparation quality, and histopathology.
      RESULTS: One-third of the patients (n = 134) had suboptimal quality of bowel
      preparation; 15% (n = 62) had fair quality, and 17% (n = 72) had poor quality.
      Limited health literacy was associated with a lower level of education (P <
      .001), diabetes (P < .001), and a higher number of chronic conditions (P < .001),
      but not quality of colonoscopy preparation. No baseline characteristics were
      associated with patient activation. In multivariable analysis, after adjusting
      for demographics and clinical characteristics, diabetes (odds ratio [OR], 2.45;
      95% confidence interval [CI], 1.14-5.25) and patient activation (OR, 2.12; 95%
      CI, 1.30-3.45) were independent predictors of suboptimal bowel preparation
      quality, but limited health literacy was not (OR, 0.76; 95% CI, 0.38-1.52).
      CONCLUSIONS: We investigated the relationship between health literacy, patient
      activation, and colonoscopy preparation quality. Lower patient activation was an
      independent predictor of suboptimal bowel preparation quality. Interventions to
      improve colonoscopy preparation quality should consider the importance of patient
      activation within their design.

PMID- 23954648
TI  - Intraluminal tubular duodenal duplication with bleeding.

PMID- 23954651
TI  - Reply: To PMID 23524129.

PMID- 23954649
TI  - Circulating inflammatory cytokines and adipokines are associated with increased
      risk of Barrett's esophagus: a case-control study.
AB  - BACKGROUND & AIMS: Obesity is associated with Barrett's esophagus (BE) and with
      changes in circulating levels of adipokines (leptin and adiponectin) and
      cytokines. Although studies have reported that adipokines and inflammatory
      cytokines are necessary for the development of BE, their role is controversial.
      METHODS: We performed a case-control study; cases (n = 141) were patients who
      underwent esophagogastroduodenoscopy and were found to have BE, which was based
      on endoscopy and histology, and controls (n = 139) were primary care patients
      eligible for screening colonoscopies who agreed to undergo
      esophagogastroduodenoscopy. We examined the association between BE and
      circulating levels of adipokines and cytokines (interleukin [IL]-1beta, IL-6, IL
      8, IL-10, and IL-12p70; tumor necrosis factor-alpha; and interferon-gamma). Cases
      and controls were compared by calculating odds ratios (ORs) and 95% confidence
      intervals (CIs) and using unadjusted and multiple logistic regression, adjusting
      for age, sex, race, waist-hip ratio, use of proton pump inhibitors and
      nonsteroidal anti-inflammatory drugs, and Helicobacter pylori infection. RESULTS:
      The adjusted ORs for BE were 2.62 (95% CI, 1.0-6.8), 5.18 (95% CI, 1.7-15.7), and
      8.02 (95% CI, 2.79-23.07) for the highest quintile vs the lowest quintile of
      levels of IL-12p70, IL-8, and leptin, respectively, but the OR was not
      significant for IL-6 (2.39; 95% CI, 0.84-6.79). The adjusted OR for BE was 0.14
      for highest quintile of IL-10 compared with lowest quintile (95% CI, 0.05-0.35)
      and 0.03 for IL-1beta >= median vs none detected (95% CI, 0.006-0.13). Higher
      levels of IL-8 and leptin and lower levels of IL-10 and IL-1beta were associated
      with the presence of long-segment (>=3 cm) and short-segment BE. There were no
      differences between cases and controls in levels of interferon-gamma, tumor
      necrosis factor-alpha, adiponectin, or insulin. CONCLUSIONS: BE is associated
      with circulating inflammatory cytokines and leptin and low levels of anti
      inflammatory cytokines. These findings could partly explain the effect of obesity
      on BE.

PMID- 23954650
TI  - Higher serum levels of vitamin D are associated with a reduced risk of
      diverticulitis.
AB  - BACKGROUND & AIMS: Recent studies have shown geographic and seasonal variations
      in hospital admissions for diverticulitis. Because this variation parallels
      differences in ultraviolet light exposure, the most important contributor to
      vitamin D status, we examined the association of prediagnostic serum levels of
      vitamin D with diverticulitis. METHODS: Among patients within the Partners
      Healthcare System who had blood drawn and serum levels of 25-hydroxyvitamin D (25
      [OH]D) measured, from 1993 through 2012, we identified 9116 patients with
      uncomplicated diverticulosis and 922 patients who developed diverticulitis that
      required hospitalization. We used multivariate logistic regression to estimate
      relative risks and 95% confidence intervals to compare serum 25(OH)D levels
      between these groups. RESULTS: Patients with uncomplicated diverticulosis had
      significantly higher mean prediagnostic serum levels of 25(OH)D (29.1 ng/mL) than
      patients with diverticulitis who required hospitalization (25.3 ng/mL; P <
      .0001). Compared with patients in the lowest quintile of 25(OH)D, the
      multivariate-adjusted relative risk for diverticulitis hospitalization was 0.49
      (95% confidence interval, 0.38-0.62; P for trend < .0001) among patients in the
      highest quintile of 25(OH)D level. Compared with patients with uncomplicated
      diverticulosis, the mean level of 25(OH)D was significantly lower for patients
      with acute diverticulitis without other sequelae (25.9 ng/mL; P < .0001; n =
      594), for patients with diverticulitis with abscess (25.8 ng/mL; P = .0095; n =
      124), for patients with diverticulitis requiring emergent laparotomy (22.7 ng/mL;
      P = .002; n = 65), and for patients with recurrent diverticulitis (23.5 ng/mL; P
      < .0001; n = 139). CONCLUSIONS: Among patients with diverticulosis, higher
      prediagnostic levels of 25(OH)D are associated significantly with a lower risk of
      diverticulitis. These data indicate that vitamin D deficiency could be involved
      in the pathogenesis of diverticulitis.

PMID- 23954652
TI  - Combatting obesity - a helping hand from the business community.

PMID- 23954654
TI  - Hematemesis and free air under the diaphragm: just another perforated duodenal
      ulcer or something more unusual?

PMID- 23954653
TI  - One number does not fit all: mapping local variations in resolution in cryo-EM
      reconstructions.
AB  - The resolution of density maps from single particle analysis is usually measured
      in terms of the highest spatial frequency to which consistent information has
      been obtained. This calculation represents an average over the entire
      reconstructed volume. In practice, however, substantial local variations in
      resolution may occur, either from intrinsic properties of the specimen or for
      technical reasons such as a non-isotropic distribution of viewing orientations.
      To address this issue, we propose the use of a space-frequency representation,
      the short-space Fourier transform, to assess the quality of a density map, voxel
      by-voxel, i.e. by local resolution mapping. In this approach, the experimental
      volume is divided into small subvolumes and the resolution determined for each of
      them. It is illustrated in applications both to model data and to experimental
      density maps. Regions with lower-than-average resolution may be mobile components
      or ones with incomplete occupancy or result from multiple conformational states.
      To improve the interpretability of reconstructions, we propose an adaptive
      filtering approach that reconciles the resolution to which individual features
      are calculated with the results of the local resolution map. 

PMID- 23954655
TI  - Ancient origins of the Mediterranean trap-door spiders of the family Ctenizidae
      (Araneae, Mygalomorphae).
AB  - The family Ctenizidae is a worldwide-distributed trapdoor spider group, with a
      modest number of genera and species but interesting biogeography. Its monophyly
      has been questioned on the basis of both morphological and molecular evidence.
      The family is represented in the Mediterranean Basin by three genera and nine
      species: Cteniza and Cyrtocarenum, mostly endemic to the region, and Ummidia,
      long considered an anthropogenic introduction to the Mediterranean because the
      bulk of its diversity is in the New World. The taxonomic status of some of the
      species and genera (e.g. Mediterranean Ummidia species or Cteniza and
      Cyrtocarenum) has been called into question due to their close morphological
      affinities. Here, we use a multilocus approach that combines DNA sequence data
      from three nuclear genes 28S rRNA, EF1gamma and H3 to investigate the origins and
      phylogenetic position of the Mediterranean taxa within the context of ctenizid
      generic-level diversity. For the first time, all known ctenizid genera are
      included in a phylogenetic analysis. Additionally, Bayesian relaxed clock methods
      and specific substitution rates are used to infer the timing of the group's
      diversification. Our results disagree with the traditional division of the family
      Ctenizidae into two subfamilies finding them polyphyletic and stress the need for
      re-evaluating the morphological characters that have been used in the group's
      classification. Time estimates indicate an ancient origin and long history of
      Mediterranean ctenizids. The present day disjunct distribution of Ummidia seems
      to be the result of the opening of the Atlantic Ocean, suggesting a former
      Laurasian distribution of the genus that is further supported by Baltic amber
      fossils. Similarly, the opening of the western Mediterranean Basin has likely
      played a key role in the diversification of both Ummidia and Cteniza, whereas the
      origin of Cyrtocarenum species preceded the breakup of the former continuous
      landmass that formed the Aegean region. Deep divergence times and reciprocal
      monophyly support the status of Cteniza and Cyrtocarenum as independent
      evolutionary lineages. Alternatively, the taxonomic status of Ummidia with regard
      to the closely related genus Conothele remains unclear; a more thorough sampling
      of the latter is needed to evaluate whether the synonymy of the two genera is
      necessary. 

PMID- 23954656
TI  - Immunopharmacological intervention for successful neural stem cell therapy: New
      perspectives in CNS neurogenesis and repair.
AB  - The pharmacological support and stimulation of endogenous and transplanted neural
      stem cells (NSCs) is a major challenge in brain repair. Trauma to the central
      nervous system (CNS) results in a distinct inflammatory response caused by local
      and infiltrating immune cells. This makes NSC-supported regeneration difficult
      due to the presence of inhibitory immune factors which are upregulated around the
      lesion site. The continual and dual role of the neuroinflammatory response leaves
      it difficult to decipher upon a single modulatory strategy. Therefore,
      understanding the influence of cytokines upon regulation of NSC self-renewal,
      proliferation and differentiation is crucial when designing therapies for CNS
      repair. There is a plethora of partially conflicting data in vitro and in vivo on
      the role of cytokines in modulating the stem cell niche and the milieu around NSC
      transplants. This is mainly due to the pleiotropic role of many factors. In order
      for cell-based therapy to thrive, treatment must be phase-specific to the injury
      and also be personalized for each patient, i.e. taking age, sex, neuroimmune and
      endocrine status as well as other key parameters into consideration. In this
      review, we will summarize the most relevant information concerning interleukin
      (IL)-1, IL-4, IL-10, IL-15, IFN-gamma, the neuropoietic cytokine family and TNF
      alpha in order to extract promising therapeutic approaches for further research.
      We will focus on the consequences of neuroinflammation on endogenous brain stem
      cells and the transplantation environment, the effects of the above cytokines on
      NSCs, as well as immunopharmacological manipulation of the microenvironment for
      potential therapeutic use.

PMID- 23954657
TI  - Polyhydroxyalkanoates production with mixed microbial cultures: from culture
      selection to polymer recovery in a high-rate continuous process.
AB  - Polyhydroxyalkanoates (PHA) production with mixed microbial cultures (MMC) has
      been investigated by means of a sequential process involving three different
      stages, consisting of a lab-scale sequencing batch reactor for MMC selection, a
      PHA accumulation reactor and a polymer extraction reactor. All stages were
      performed under continuous operation for at least 4 months to check the overall
      process robustness as well as the related variability of polymer composition and
      properties. By operating both biological stages at high organic loads (8.5 and
      29.1 gCOD/Ld, respectively) with a synthetic mixture of acetic and propionic
      acid, it was possible to continuously produce PHA at 1.43 g/Ld with stable
      performance (overall, the storage yield was 0.18 COD/COD). To identify the
      optimal operating conditions of the extraction reactor, two digestion solutions
      have been tested, NaOH (1m) and NaClO (5% active Cl2). The latter resulted in the
      best performance both in terms of yield of polymer recovery (around 100%, w/w)
      and purity (more than 90% of PHA content in the residual solids, on a weight
      basis). In spite of the stable operating conditions and performance, a large
      variation was observed for the HV content, ranging between 4 and 20 (%, w/w) for
      daily samples after accumulation and between 9 and 13 (%, w/w) for weekly average
      samples after extraction and lyophilization. The molecular weight of the produced
      polymer ranged between 3.4 * 10(5) and 5.4 * 10(5)g/mol with a large
      polydispersity index. By contrast, TGA and DSC analysis showed that the thermal
      polymer behavior did not substantially change over time, although it was strongly
      affected by the extraction agent used (NaClO or NaOH).

PMID- 23954658
TI  - Determination of inorganic anions in saliva by electroosmotic flow controlled
      counterflow isotachophoretic stacking under field-amplified sample injection.
AB  - Under a strong counter-electroosmotic flow, five salivary inorganic anions,
      bromide, iodide, nitrite, nitrate and thiocyanate were determined by field
      amplified sample injection in combination with isotachophoretic stacking.
      Separation and concentration conditions were investigated. A terminating
      electrolyte, 5mM borate, was added in the sample. Under the optimized conditions,
      Br(-), I(-) and SCN(-) were concentrated online using 150mM HCl-Tris buffer at pH
      7.8 in a bare fused capillary, providing more than ten thousand of sensitivity
      enrichment compared with normal injections. The relative standard deviations
      (RSDs, n=5) were less than 1% in migration times, 8% in peak areas. Using direct
      UV detection at 200nm and 226nm, the limits of detection (LODs, S/N=3) were of
      0.002-0.01MUM. Unfortunately, NO2(-) and NO3(-) could be observed in purified or
      deionized water. Therefore, a low dilution factor was applied to saliva samples.
      Due to the matrix effect, samples were injected in a shorter time, and standard
      addition method was applied to determine all the five inorganic anions in saliva.
      The RSDs of the migration times and peak areas were in a range of 0.2-0.4% and
      3.0-4.0%, respectively. The LODs were 0.2-2.0MUM. The salivary levels of the
      anions obtained were in accord with the reference data. The external standard
      method can not be adapted to real samples due to biases caused by electrokinetic
      injection and errors from high dilutions. 

PMID- 23954659
TI  - Reliable quantitation of beta-hydroxyethoxyacetic acid in human urine by an
      isotope-dilution GC-MS procedure.
AB  - An analytical method for the determination of beta-hydroxyethoxyacetic acid
      (HEAA), the main urinary metabolite of 1,4-dioxane was developed and validated.
      The presented method involves liquid-liquid extraction of HEAA from the urine
      samples, followed by silylation and subsequent analytical separation and
      detection using GC-MS. The method is characterized by its simple and fast sample
      preparation in combination with a robust chromatography. The use of isotope
      dilution analysis enables an efficient compensation of matrix related effects and
      analyte losses due to sample workup. The excellent reliability and
      reproducibility of the method is demonstrated by the good accuracy and precision
      data. Within-day precision and day-to-day precision ranged from 0.6 to 1.2% and
      1.5 to 2.6%, respectively. The mean relative recovery of the method was found to
      be 98-101%. The LOD and LOQ of HEAA were determined to be 0.2mg/L and 0.6mg/L,
      respectively. In summary, the presented analytical method is well suited to be
      used for routine biomonitoring of occupational exposure to 1,4-dioxane. 

PMID- 23954660
TI  - The European trauma course--trauma teaching goes European.

PMID- 23954661
TI  - The future of E-CPR: a joint venture.

PMID- 23954662
TI  - Reply to letter: effect of flow rate, humidifier dome and water volume on
      maximising heated, humidified gas use for neonatal resuscitation-a response.

PMID- 23954663
TI  - Effect of flow rate and humidifier. What are the limits of these interactions?

PMID- 23954665
TI  - Lazarus phenomenon: knowledge, attitude and practice.

PMID- 23954664
TI  - Pushing harder, pushing faster, minimizing interruptions... but falling short of
      2010 cardiopulmonary resuscitation targets during in-hospital pediatric and
      adolescent resuscitation.
AB  - AIM: The objective of this study was to evaluate the effect of instituting the
      2010 Basic Life Support Guidelines on in-hospital pediatric and adolescent
      cardiopulmonary resuscitation (CPR) quality. We hypothesized that quality would
      improve, but that targets for chest compression (CC) depth would be difficult to
      achieve. METHODS: Prospective in-hospital observational study comparing CPR
      quality 24 months before and after release of the 2010 Guidelines. CPR
      recording/feedback-enabled defibrillators collected CPR data (rate (CC/min),
      depth (mm), CC fraction (CCF, %), leaning (%>2.5kg)). Audiovisual feedback for
      depth was: 2005, >=38mm; 2010, >=50mm; for rate: 2005, >=90 and <=120CC/min;
      2010, >=100 and <=120CC/min. The primary outcome was average event depth compared
      with Student's t-test. RESULTS: 45 CPR events (25 before; 20 after) occurred,
      resulting in 1336 thirty-second epochs (909 before; 427 after). Compared to 2005,
      average event depth (50+/-13mm vs. 43+/-9mm; p=0.047), rate (113+/-11CC/min vs.
      104+/-8CC/min; p<0.01), and CCF (0.94 [0.93, 0.96] vs. 0.9 [0.85, 0.94]; p=0.013)
      increased during 2010. CPR epochs during the 2010 period more likely to meet
      Guidelines for CCF (OR 1.7; CI95: 1.2-2.4; p<0.01), but less likely for rate (OR
      0.23; CI95: 0.12-0.44; p<0.01), and depth (OR 0.31; CI95: 0.12-0.86; p=0.024).
      CONCLUSIONS: Institution of the 2010 Guidelines was associated with increased CC
      depth, rate, and CC fraction; yet, achieving 2010 targets for rate and depth was
      difficult.

PMID- 23954666
TI  - Clinical examination for prognostication in comatose cardiac arrest patients.
AB  - OBJECTIVE: To build new algorithms for prognostication of comatose cardiac arrest
      patients using clinical examination, and investigate whether therapeutic
      hypothermia influences the value of the clinical examination. METHODS: From 2000
      to 2007, 500 consecutive patients in non-traumatic coma were prospectively
      enrolled, 200 of whom were post-cardiac arrest. Outcome was determined by
      modified Rankin Scale (mRS) score at 6 months, with mRS<=3 indicating good
      outcome. The clinical examination was performed on days 0, 1, 3 and 7 post
      arrest, and clinical variables analyzed for importance in prognostication of
      outcome. A classification and regression tree analysis (CART) was used to develop
      a predictive algorithm. RESULTS: Good outcome was achieved in 9.9% of patients.
      In CART analysis, motor response was often chosen as a root node, and spontaneous
      eye movements, pupillary reflexes, eye opening and corneal reflexes were often
      chosen as splitting nodes. Over 8% of patients with absent or extensor motor
      response on day 3 achieved a good outcome, as did 2 patients with myoclonic
      status epilepticus. The odds of achieving a good outcome were lower in patients
      who suffered asystole (OR 0.187, 95% CI: 0.039-0.875, p=0.033) compared with
      ventricular fibrillation or non-perfusing ventricular tachycardia, but some still
      achieved good outcome. The absence of pupillary and corneal reflexes on day 3
      remained highly reliable for predicting poor outcome, regardless of therapeutic
      hypothermia utilization. CONCLUSION: The clinical examination remains central to
      prognostication in comatose cardiac arrest patients in the modern area. Future
      studies should incorporate the clinical examination along with modern technology
      for accurate prognostication.

PMID- 23954668
TI  - Behavioral assessment of emotional and motivational appraisal during visual
      processing of emotional scenes depending on spatial frequencies.
AB  - Previous studies performed on visual processing of emotional stimuli have
      revealed preference for a specific type of visual spatial frequencies (high
      spatial frequency, HSF; low spatial frequency, LSF) according to task demands.
      The majority of studies used a face and focused on the appraisal of the emotional
      state of others. The present behavioral study investigates the relative role of
      spatial frequencies on processing emotional natural scenes during two explicit
      cognitive appraisal tasks, one emotional, based on the self-emotional experience
      and one motivational, based on the tendency to action. Our results suggest that
      HSF information was the most relevant to rapidly identify the self-emotional
      experience (unpleasant, pleasant, and neutral) while LSF was required to rapidly
      identify the tendency to action (avoidance, approach, and no action). The
      tendency to action based on LSF analysis showed a priority for unpleasant stimuli
      whereas the identification of emotional experience based on HSF analysis showed a
      priority for pleasant stimuli. The present study confirms the interest of
      considering both emotional and motivational characteristics of visual stimuli. 

PMID- 23954667
TI  - A new treatment for human malignant melanoma targeting L-type amino acid
      transporter 1 (LAT1): a pilot study in a canine model.
AB  - L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system
      L, transports branched or aromatic amino acids essential for fundamental cellular
      activities such as cellular growth, proliferation and maintenance. This amino
      acid transporter recently has received attention because of its preferential and
      up-regulated expression in a variety of human tumors in contrast to its limited
      distribution and low-level expression in normal tissues. In this study, we
      explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for
      human malignant melanomas (MM) using canine spontaneous MM as a model for human
      MM. A comparative study of LAT expression was performed in 48 normal tissues,
      25MM tissues and five cell lines established from MM. The study observed LAT1
      mRNA levels from MM tissues and cell lines that were significantly (P<0.01)
      higher than in normal tissues. Additionally, MM with distant metastasis showed a
      higher expression than those without distant metastasis. Functional analysis of
      LAT1 was performed on one of the five cell lines, CMeC-1. [(3)H]l-Leucine uptake
      and cellular growth activities in CMeC-1 were inhibited in a dose-dependent
      manner by selective LAT1 inhibitors (2-amino-2-norbornane-carboxylic acid, BCH
      and melphalan, LPM). Inhibitory growth activities of various conventional anti
      cancer drugs, including carboplatin, cyclophosphamide, dacarbazine, doxorubicin,
      mitoxantrone, nimustine, vinblastine and vincristine, were significantly (P<0.05)
      enhanced by combination use with BCH or LPM. These findings suggest that LAT1
      could be a new therapeutic target for MM.

PMID- 23954669
TI  - The "simulation" of the facial expression of emotions in case of short and long
      stimulus duration. The effect of pre-motor cortex inhibition by rTMS.
AB  - Embodied cognition model states that the "simulation process" is necessary to the
      recognition of emotional significance of face. The present research explored the
      contribution of frontal motor brain components (i.e. mainly premotor area) to
      embodied cognition by using rTMS stimulation, to produce a temporary disruption
      of this specific cortical site. Secondly, short and long stimulus duration
      conditions were included to verify the contribution of the "simulation process"
      in response to overt and covert emotional stimulus comprehension. Nineteen
      subjects were asked to detect emotion/no emotion (anger, fear, happiness,
      neutral) in these two experimental conditions, by using a backward masking
      procedure. Five-second rTMS (1Hz) was delivered before the stimulus onset. False
      alarms (Fa) and RTs increased and Hits decreased when frontal premotor brain
      activity was disrupted, specifically in response to anger and fear, for both long
      and shortduration condition. Thus, the present results highlight the main role of
      the frontal motor system for emotion facial expression processing. 

PMID- 23954670
TI  - Targeted vaccination programme successful in reducing acute hepatitis B in men
      having sex with men in Amsterdam, the Netherlands.
AB  - BACKGROUND & AIMS: In the Netherlands, transmission of hepatitis B virus occurs
      mainly within behavioural high-risk groups, such as in men who have sex with men.
      Therefore, a vaccination programme has targeted these high-risk groups. This
      study evaluates the impact of the vaccination programme targeting Amsterdam's
      large population of men who have sex with men from 1998 through 2011. METHODS: We
      used Amsterdam data from the national database of the vaccination programme for
      high-risk groups (January 1, 1998 to December 31, 2011). Programme and
      vaccination coverage were estimated with population statistics. Incidence of
      acute hepatitis B was analyzed with notification data from the Amsterdam Public
      Health Service (1992-2011). Mathematical modelling accounting for vaccination
      data and trends in sexual risk behaviour was used to explore the impact of the
      programme. RESULTS: At the end of 2011, programme coverage was estimated at 41%
      and vaccination coverage from 30% to 38%. Most participants (67%) were recruited
      from the outpatient department for sexually transmitted infections and outreach
      locations such as saunas and gay bars. Incidence of acute hepatitis B dropped
      sharply after 2005. The mathematical model in which those who engage most in high
      risk sex are vaccinated, best explained the decline in incidence. CONCLUSIONS:
      Transmission of hepatitis B virus among Amsterdam's men who have sex with men has
      decreased, despite ongoing high-risk sexual behaviour. Vaccination programmes
      targeting men who have sex with men do not require full coverage; they may be
      effective when those who engage most in high-risk sex are reached.

PMID- 23954671
TI  - Effective albumin concentration and cirrhosis mortality: from concept to reality.

PMID- 23954672
TI  - Functionalized ultra-low fouling carboxy- and hydroxy-functional surface
      platforms: functionalization capacity, biorecognition capability and resistance
      to fouling from undiluted biological media.
AB  - The non-specific binding of non-target species to functionalized surfaces of
      biosensors continues to be challenge for biosensing in real-world media. Three
      different low-fouling and functionalizable surface platforms were employed to
      study the effect of functionalization on fouling resistance from several types of
      undiluted media including blood plasma and food media. The surface platforms
      investigated in this work included two polymer brushes: hydroxy-functional poly(2
      hydroxyethyl methacrylate) (pHEMA) and carboxy-functional poly(carboxybetaine
      acrylamide) (pCBAA), and a standard OEG-based carboxy-functional alkanethiolate
      self-assembled monolayer (AT-SAM). The wet and dry polymer brushes were analyzed
      by AFM, ellipsometry, FT-IRRAS, and surface plasmon resonance (SPR). The surfaces
      were functionalized by the covalent attachment of antibodies, streptavidin, and
      oligonucleotides and the binding and biorecognition characteristics of the
      coatings were compared. We found that functionalization did not substantially
      affect the ultra-low fouling properties of pCBAA (plasma fouling of ~20
      ng/cm(2)), a finding in contrast with pHEMA that completely lost its resistance
      to fouling after the activation of hydroxyl groups. Blocking a functionalized AT
      SAM covalently with BSA decreased fouling down to the level comparable to
      unblocked pCBAA. However, the biorecognition capability of blocked functionalized
      AT-SAM was poor in comparison with functionalized pCBAA. Limits of detection of
      Escherichia coli O157:H7 in undiluted milk were determined to be 6*10(4),
      8*10(5), and 6*10(5) cells/ml for pCBAA, pHEMA, and AT-SAM-blocked, respectively.
      Effect of analyte size on biorecognition activity of functionalized coatings was
      investigated and it was shown that the best performance in terms of overall
      fouling resistance and biorecognition capability is provided by pCBAA.

PMID- 23954673
TI  - Co-immobilization of glucoamylase and glucose oxidase for electrochemical
      sequential enzyme electrode for starch biosensor and biofuel cell.
AB  - A novel electrochemical sequential biosensor was constructed by co-immobilizing
      glucoamylase (GA) and glucose oxidase (GOD) on the multi-walled carbon nanotubes
      (MWNTs)-modified glassy carbon electrode (GCE) by chemical crosslinking method,
      where glutaraldehyde and bovine serum albumin was used as crosslinking and
      blocking agent, respectively. The proposed biosensor (GA/GOD/MWNTs/GCE) is
      capable of determining starch without using extra sensors such as Clark-type
      oxygen sensor or H2O2 sensor. The current linearly decreased with the increasing
      concentration of starch ranging from 0.005% to 0.7% (w/w) with the limit of
      detection of 0.003% (w/w) starch. The as-fabricated sequential biosensor can be
      applicable to the detection of the content of starch in real samples, which are
      in good accordance with traditional Fehling's titration. Finally, a stable
      starch/O2 biofuel cell was assembled using the GA/GOD/MWNTs/GCE as bioanode and
      laccase/MWNTs/GCE as biocathode, which exhibited open circuit voltage of ca. 0.53
      V and the maximum power density of 8.15 MUW cm(-2) at 0.31 V, comparable with the
      other glucose/O2 based biofuel cells reported recently. Therefore, the proposed
      biosensor exhibited attractive features such as good stability in weak acidic
      buffer, good operational stability, wide linear range and capable of
      determination of starch in real samples as well as optimal bioanode for the
      biofuel cell.

PMID- 23954674
TI  - Ultrasensitive photoelectrochemical immunoassay of indole-3-acetic acid based on
      the MPA modified CdS/RGO nanocomposites decorated ITO electrode.
AB  - A novel ultrasensitive photoelectrochemical immunosensor was fabricated based on
      3-mercaptopropionic acid stabilized CdS/reduced graphene oxide (MPA-CdS/RGO)
      nanocomposites for indole-3-acetic acid (IAA) detection. The MPA-CdS/RGO
      nanocomposites were synthesized by in situ solvothermal growth of triangulated
      pyramidal CdS nanoparticles on the RGO sheet. 3-Mercaptopropionic acid (MPA) was
      employed as the modifier and bridge to immobilize the antibody. The
      nanocomposites were characterized by X-ray diffraction, transmission electron
      microscopy, scanning electron microscopy and UV/vis spectra. The results showed
      that the MPA-CdS/RGO nanocomposites revealed enhanced photocurrent response due
      to excellent electron transport properties of RGO and the improved assembly of
      CdS nanoparticles onto RGO sheet with the introduction of MPA. Based on the
      dependence of the photocurrent decline on the concentration of IAA, the proposed
      photoelectrochemical immunosensor for IAA depicted a linear range from 0.1 to
      1000 ng/mL with a lower detection limit (0.05 ng/mL). The high sensitivity,
      reproducibility and specificity of the method permitted the method suitable to be
      used in real samples.

PMID- 23954675
TI  - Cholinergic modulation of primary afferent glutamatergic transmission in rat
      medullary dorsal horn neurons.
AB  - Although muscarinic acetylcholine (mACh) receptors are expressed in trigeminal
      ganglia, it is still unknown whether mACh receptors modulate glutamatergic
      transmission from primary afferents onto medullary dorsal horn neurons. In this
      study, we have addressed the cholinergic modulation of primary afferent
      glutamatergic transmission using a conventional whole cell patch clamp technique.
      Glutamatergic excitatory postsynaptic currents (EPSCs) were evoked from primary
      afferents by electrical stimulation of trigeminal tract and monosynaptic EPSCs
      were recorded from medullary dorsal horn neurons of rat horizontal brain stem
      slices. Muscarine and ACh reversibly and concentration-dependently decreased the
      amplitude of glutamatergic EPSCs and increased the paired-pulse ratio. In
      addition, muscarine reduced the frequency of miniature EPSCs without affecting
      the current amplitude, suggesting that muscarine acts presynaptically to decrease
      the probability of glutamate release onto medullary dorsal horn neurons. The
      muscarine-induced decrease of glutamatergic EPSCs was significantly occluded by
      methoctramine or AF-DX116, M2 receptor antagonists, but not pirenzepine, J104129
      and MT-3, selective M1, M3 and M4 receptor antagonists. The muscarine-induced
      decrease of glutamatergic EPSCs was highly dependent on the extracellular Ca2+
      concentration. Physostigmine and clinically available acetylcholinesterase
      inhibitors, such as rivastigmine and donepezil, significantly shifted the
      concentration-inhibition relationship of ACh for glutamatergic EPSCs. These
      results suggest that muscarine acts on presynaptic M2 receptors to inhibit
      glutamatergic transmission by reducing the Ca2+ influx into primary afferent
      terminals, and that M2 receptor agonists and acetylcholinesterase inhibitors
      could be, at least, potential targets to reduce nociceptive transmission from
      orofacial tissues.

PMID- 23954676
TI  - Repeated asenapine treatment produces a sensitization effect in two preclinical
      tests of antipsychotic activity.
AB  - Among several commonly used atypical antipsychotic drugs, olanzapine and
      risperidone cause a sensitization effect in the conditioned avoidance response
      (CAR) and phencyclidine (PCP)-induced hyperlocomotion paradigms--two well
      established animal tests of antipsychotic drugs, whereas clozapine causes a
      tolerance effect. Asenapine is a novel antipsychotic drug recently approved for
      the treatment of schizophrenia and manic disorders. It shares several receptor
      binding sites and behavioral features with other atypical antipsychotic drugs.
      However, it is not clear what type of repeated effect (sensitization or
      tolerance) asenapine would induce, and whether such an effect is transferrable to
      other atypicals. In this study, male adult Sprague-Dawley rats were first
      repeatedly tested with asenapine (0.05, 0.10 or 0.20 mg/kg, sc) for avoidance
      response or PCP (3.20 mg/kg, sc)-induced hyperlocomotion daily for 5 consecutive
      days. After 2-3 days of retraining/drug-free recovery, they were then challenged
      with asenapine (0.10 mg/kg, sc), followed by olanzapine (0.50 mg/kg, sc) and
      clozapine (2.50 mg/kg, sc). During the 5-day drug test period (the induction
      phase), repeated asenapine treatment progressively increased its inhibition of
      avoidance response and PCP-induced hyperlocomotion in a dose-dependent fashion.
      On the asenapine and olanzapine challenge tests (the expression phase), rats
      previously treated with asenapine still showed significantly lower avoidance
      response and lower PCP-induced hyperlocomotion than those previously treated with
      vehicle. An increased reactivity to clozapine challenge in prior asenapine
      treated rats was also found in the PCP-induced hyperlocomotion test. These
      findings suggest that asenapine is capable of inducing a sensitization effect and
      a cross-sensitization to olanzapine and clozapine (to a lesser extent). Because
      the behavioral profile of asenapine in both tests is similar to that of
      olanzapine, but different from that of clozapine, we suggest that asenapine
      resembles olanzapine to a greater extent than clozapine in its therapeutic and
      side effect profiles.

PMID- 23954678
TI  - Protective effect of serofendic acid, administered intravenously, on cerebral
      ischemia-reperfusion injury in rats.
AB  - Serofendic acid is a low-molecular-weight compound extracted from fetal calf
      serum. We previously reported that intracerebroventricular administration of
      serofendic acid prevents cerebral ischemia-reperfusion injury. However, the
      effect of peripheral administration of serofendic acid on cerebral ischemia
      reperfusion injury has not been examined. In the present study, we investigated
      the effect of intravenous administration of serofendic acid against cerebral
      ischemia-reperfusion injury using transient middle cerebral artery occlusion
      model rats. Serofendic acid (10mg/kg) administrated three times, including 30min
      before the onset of ischemia, just after the onset of ischemia and just before
      reperfusion reduced the infarct volume and improved the neurological dysfunction
      induced by ischemia-reperfusion without affecting regional cerebral blood flow or
      physiological parameters. However, there were no protective effects when
      serofendic acid (30mg/kg) was only administered once at 30min before the onset of
      ischemia, just after the onset of ischemia, or just before reperfusion. Our
      results reveal the importance of maintaining the blood concentration of
      serofendic acid for preventing cerebral ischemia-reperfusion injury. 

PMID- 23954680
TI  - Fructose restrains fibrillogenesis in human serum albumin.
AB  - The endogenous deposition of protein aggregates with fibrillar morphology is
      known to govern the genesis of several neurodisorders. The investigation of
      naturally occurring small molecules which can restrict the fibrillation process
      can help in the design of rational therapeutics for neurodegenerative diseases.
      We report the inhibition of HSA fibrillation in the presence of naturally
      occurring sugars such as glucose, fructose, ribose and sucrose with fructose
      being the most potent. We have characterized the inhibitory potency of the
      sugars, using different spectroscopic and microscopic techniques. 

PMID- 23954679
TI  - DNA methylation markers in the postnatal developing rat brain.
AB  - In spite of intense interest in how altered epigenetic processes including DNA
      methylation may contribute to psychiatric and neurodevelopmental disorders, there
      is a limited understanding of how methylation processes change during early
      postnatal brain development. The present study used in situ hybridization to
      assess mRNA expression for the three major DNA methyltranserases (DNMTs)--DNMT1,
      DNMT3a and DNMT3b--in the developing rat brain at seven developmental timepoints:
      postnatal days (P) 1, 4, 7, 10, 14, 21, and 75. We also assessed 5-methylcytosine
      levels (an indicator of global DNA methylation) in selected brain regions during
      the first three postnatal weeks. DNMT1, DNMT3a and DNMT3b mRNAs are widely
      expressed throughout the adult and postnatal developing rat brain. Overall, DNMT
      mRNA levels reached their highest point in the first week of life and gradually
      decreased over the first three postnatal weeks within the hippocampus, amygdala,
      striatum, cingulate and lateral septum. Global DNA methylation levels did not
      follow this developmental pattern; methylation levels gradually increased over
      the first three postnatal weeks in the hippocampus, and remained stable in the
      developing amygdala and prefrontal cortex. Our results contribute to a growing
      understanding of how DNA methylation markers unfold in the developing brain, and
      highlight how these developmental processes may differ within distinct brain
      regions.

PMID- 23954677
TI  - More surprises lying ahead. The endocannabinoids keep us guessing.
AB  - The objective of this review is to point out some important facts that we don't
      know about endogenous cannabinoids - lipid-derived signaling molecules that
      activate CB1 cannabinoid receptors and play key roles in motivation, emotion and
      energy balance. The first endocannabinoid substance to be discovered, anandamide,
      was isolated from brain tissue in 1992. Research has shown that this molecule is
      a bona fide brain neurotransmitter involved in the regulation of stress responses
      and pain, but the molecular mechanisms that govern its formation and the neural
      pathways in which it is employed are still unknown. There is a general consensus
      that enzyme-mediated cleavage, catalyzed by fatty acid amide hydrolase (FAAH),
      terminates the biological actions of anandamide, but there are many reasons to
      believe that other as-yet-unidentified proteins are also involved in this
      process. We have made significant headway in understanding the second arrived in
      the endocannabinoid family, 2-arachidonoyl-sn-glycerol (2-AG), which was
      discovered three years after anandamide. Researchers have established some of the
      key molecular players involved in 2-AG formation and deactivation, localized them
      to specific synaptic components, and showed that their assembly into a multi
      molecular protein complex (termed the '2-AG signalosome') allows 2-AG to act as a
      retrograde messenger at excitatory synapses of the brain. Basic questions that
      remain to be answered pertain to the exact molecular composition of the 2-AG
      signalosome, its regulation by neural activity and its potential role in the
      actions of drugs of abuse such as Delta(9)-THC and cocaine. This article is part
      of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

PMID- 23954681
TI  - MADYMO simulation of children in cycle accidents: a novel approach in risk
      assessment.
AB  - Head injuries are a significant cause of death and injury to child cyclists both
      on and off the road. Current evaluations of the effectiveness of cycle helmets
      rely on simplified mechanical testing or the analysis of aggregated accident
      statistics. This paper presents a direct evaluation of helmet efficacy by using
      computational modelling to simulate a range of realistic accident scenarios,
      including loss of control, collision with static objects and vehicle impact. A 6
      year-old cyclist was modelled (as a Hybrid III 6-year-old dummy), in addition to
      a typical children's bicycle and a vehicle using the MADYMO dynamics software
      package. Simulations were performed using ranges of cyclist position, cycle speed
      and vehicle speed with and without a helmet that meets current standards. Wearing
      a cycle helmet was found to reduce the probability of head injuries, reducing the
      average probability of fatality over the scenarios studied from 40% to 0.3%.
      Similarly, helmet wearing reduced the probability of neck injuries (average
      probability of fatality reduced from 11% to 1%). There was no evidence that
      helmet wearing increased the severity of brain or neck injuries caused by
      rotational accelerations; in fact these were slightly reduced. Similarly, there
      was no evidence that increased cycling speed, such as might result from helmet
      related risk compensation, increased the probability of head injury. 

PMID- 23954683
TI  - International transferability of accident modification functions for horizontal
      curves.
AB  - Studies of the relationship between characteristics of horizontal curves and
      accident rate have been reported in several countries. The characteristic most
      often studied is the radius of a horizontal curve. Functions describing the
      relationship between the radius of horizontal curves and accident rate have been
      developed in Australia, Canada, Denmark, Germany, Great Britain, New Zealand,
      Norway, Portugal, Sweden, and the United States. Other characteristics of
      horizontal curves that have been studied include deflection angle, curve length,
      the presence of transition curves, super-elevation in curves and distance to
      adjacent curves. This paper assesses the international transferability of
      mathematical functions (accident modification functions) that have been developed
      to relate the radius of horizontal curves to their accident rate. The main
      research problem is whether these functions are similar, which enhances
      international transferability, or dissimilar, which reduces international
      transferability. Accident modification functions for horizontal curve radius
      developed in the countries listed above are synthesised. The sensitivity of the
      functions to other characteristics of curves than radius is examined. Accident
      modification functions developed in different countries have important
      similarities. The functions diverge with respect to accident rate in the sharpest
      curves. 

PMID- 23954682
TI  - Observational study of child restraining practice on Norwegian high-speed roads:
      restraint misuse poses a major threat to child passenger safety.
AB  - OBJECTIVE: Restraint misuse and other occupant safety errors are the major cause
      of fatal and, severe injuries among child passengers in motor vehicle collisions.
      The main objectives of the present, study were to provide estimates of
      restraining practice among children younger than 16 years, traveling on Norwegian
      high-speed roads, and to uncover the high-risk groups associated with, restraint
      misuse and other safety errors. METHODS: A cross-sectional observational study
      was performed in conjunction with regular traffic, control posts on high-speed
      roads. The seating and restraining of child occupants younger than 16, years were
      observed, the interior environment of the vehicles was examined, and a
      structured, interview of the driver was conducted according to a specific
      protocol. RESULTS: In total, 1260 child occupants aged 0-15 years were included
      in the study. Misuse of restraints, was observed in 38% of cases, with this being
      severe or critical in 24%. The presence of restraint, misuse varied significantly
      with age (p<0.001), with the frequency being highest among child, occupants in
      the age group 4-7 years. The most common error in this group was improperly
      routed, seat belts. The highest frequency of severe and critical errors was
      observed among child occupants in, the age group 0-3 years. The most common
      errors were loose or improperly routed harness straps and, incorrect
      installations of the child restraint system. Moreover, 24% of the children were
      seated in, vehicles with heavy, unsecured objects in the passenger compartment
      and/or the trunk that were, likely to move into the compartment upon impact and
      cause injury. No totally unrestrained children, were observed. CONCLUSIONS: This
      study provides a detailed description of the characteristics of restraint misuse
      and, the occupant's exposure to unsecured objects. Future education and awareness
      campaigns should, focus on children aged <8 years. The main challenges are to
      ensure correct routing and tightness of, harness straps and seat belts, correct
      installation of child restraints, and avoidance of premature, graduation from
      child restraints to seat belts only. Information campaigns should also advocate
      the use, of chest clips and address the potential risks of hard, heavy objects in
      the passenger compartment and, the importance of the placement and strapping of
      heavy objects in the trunk.

PMID- 23954684
TI  - Evaluating the double Poisson generalized linear model.
AB  - The objectives of this study are to: (1) examine the applicability of the double
      Poisson (DP) generalized linear model (GLM) for analyzing motor vehicle crash
      data characterized by over- and under-dispersion and (2) compare the performance
      of the DP GLM with the Conway-Maxwell-Poisson (COM-Poisson) GLM in terms of
      goodness-of-fit and theoretical soundness. The DP distribution has seldom been
      investigated and applied since its first introduction two decades ago. The hurdle
      for applying the DP is related to its normalizing constant (or multiplicative
      constant) which is not available in closed form. This study proposed a new method
      to approximate the normalizing constant of the DP with high accuracy and
      reliability. The DP GLM and COM-Poisson GLM were developed using two observed
      over-dispersed datasets and one observed under-dispersed dataset. The modeling
      results indicate that the DP GLM with its normalizing constant approximated by
      the new method can handle crash data characterized by over- and under-dispersion.
      Its performance is comparable to the COM-Poisson GLM in terms of goodness-of-fit
      (GOF), although COM-Poisson GLM provides a slightly better fit. For the over
      dispersed data, the DP GLM performs similar to the NB GLM. Considering the fact
      that the DP GLM can be easily estimated with inexpensive computation and that it
      is simpler to interpret coefficients, it offers a flexible and efficient
      alternative for researchers to model count data. 

PMID- 23954685
TI  - Evaluating alternate discrete outcome frameworks for modeling crash injury
      severity.
AB  - This paper focuses on the relevance of alternate discrete outcome frameworks for
      modeling driver injury severity. The study empirically compares the ordered
      response and unordered response models in the context of driver injury severity
      in traffic crashes. The alternative modeling approaches considered for the
      comparison exercise include: for the ordered response framework-ordered logit
      (OL), generalized ordered logit (GOL), mixed generalized ordered logit (MGOL) and
      for the unordered response framework-multinomial logit (MNL), nested logit (NL),
      ordered generalized extreme value logit (OGEV) and mixed multinomial logit (MMNL)
      model. A host of comparison metrics are computed to evaluate the performance of
      these alternative models. The study provides a comprehensive comparison exercise
      of the performance of ordered and unordered response models for examining the
      impact of exogenous factors on driver injury severity. The research also explores
      the effect of potential underreporting on alternative frameworks by artificially
      creating an underreported data sample from the driver injury severity sample. The
      empirical analysis is based on the 2010 General Estimates System (GES) data base
      a nationally representative sample of road crashes collected and compiled from
      about 60 jurisdictions across the United States. The performance of the
      alternative frameworks are examined in the context of model estimation and
      validation (at the aggregate and disaggregate level). Further, the performance of
      the model frameworks in the presence of underreporting is explored, with and
      without corrections to the estimates. The results from these extensive analyses
      point toward the emergence of the GOL framework (MGOL) as a strong competitor to
      the MMNL model in modeling driver injury severity. 

PMID- 23954686
TI  - Intersection assistance: a safe solution for older drivers?
AB  - Within the next few decades, the number of older drivers operating a vehicle will
      increase rapidly (Eurostat, 2011). As age increases so does physical
      vulnerability, age-related impairments, and the risk of being involved in a fatal
      crashes. Older drivers experience problems in driving situations that require
      divided attention and decision making under time pressure as reflected by their
      overrepresentation in at-fault crashes on intersections. Advanced Driver
      Assistance Systems (ADAS) especially designed to support older drivers crossing
      intersections might counteract these difficulties. In a longer-term driving
      simulator study, the effects of an intersection assistant on driving were
      evaluated. 18 older drivers (M=71.44 years) returned repeatedly completing a ride
      either with or without a support system in a driving simulator. In order to test
      the intersection assistance, eight intersections were depicted for further
      analyses. Results show that ADAS affects driving. Equipped with ADAS, drivers
      allocated more attention to the road center rather than the left and right,
      crossed intersections in shorter time, engaged in higher speeds, and crossed more
      often with a critical time-to-collision (TTC) value. The implications of results
      are discussed in terms of behavioral adaptation and safety. 

PMID- 23954687
TI  - The influence of economic incentives linked to road safety indicators on
      accidents: the case of toll concessions in Spain.
AB  - The goal of this paper is to evaluate whether the incentives incorporated in toll
      highway concession contracts in order to encourage private operators to adopt
      measures to reduce accidents are actually effective at improving safety. To this
      end, we implemented negative binomial regression models using information about
      highway characteristics and accident data from toll highway concessions in Spain
      from 2007 to 2009. Our results show that even though road safety is highly
      influenced by variables that are not managed by the contractor, such as the
      annual average daily traffic (AADT), the percentage of heavy vehicles on the
      highway, number of lanes, number of intersections and average speed; the
      implementation of these incentives has a positive influence on the reduction of
      accidents and injuries. Consequently, this measure seems to be an effective way
      of improving safety performance in road networks. 

PMID- 23954689
TI  - Exploring the effects of driving experience on hazard awareness and risk
      perception via real-time hazard identification, hazard classification, and rating
      tasks.
AB  - This study investigated the effects of driving experience on hazard awareness and
      risk perception skills. These topics have previously been investigated
      separately, yet a novel approach is suggested where hazard awareness and risk
      perception are examined concurrently. Young, newly qualified drivers, experienced
      drivers, and a group of commercial drivers, namely, taxi drivers performed three
      consecutive tasks: (1) observed 10 short movies of real-world driving situations
      and were asked to press a button each time they identified a hazardous situation;
      (2) observed one of three possible sub-sets of 8 movies (out of the 10 they have
      seen earlier) for the second time, and were asked to categorize them into an
      arbitrary number of clusters according to the similarity in their hazardous
      situation; and (3) observed the same sub-set for a third time and following each
      movie were asked to rate its level of hazardousness. The first task is considered
      a real-time identification task while the other two are performed using
      hindsight. During it participants' eye movements were recorded. Results showed
      that taxi drivers were more sensitive to hidden hazards than the other driver
      groups and that young-novices were the least sensitive. Young-novice drivers also
      relied heavily on materialized hazards in their categorization structure. In
      addition, it emerged that risk perception was derived from two major components:
      the likelihood of a crash and the severity of its outcome. Yet, the outcome was
      rarely considered under time pressure (i.e., in real-time hazard identification
      tasks). Using hindsight, when drivers were provided with the opportunity to rate
      the movies' hazardousness more freely (rating task) they considered both
      components. Otherwise, in the categorization task, they usually chose the
      severity of the crash outcome as their dominant criterion. Theoretical and
      practical implications are discussed. 

PMID- 23954690
TI  - Factors associated with the hospital admission of consumer product-related
      injuries treated in U.S. hospital emergency departments.
AB  - While unintentional injuries and hazard patterns involving consumer products have
      been studied extensively in recent years, little attention has focused on the
      characteristics of those who are hospitalized after treatment in emergency
      departments, as opposed to those treated and released. This study quantifies the
      impact of the age and sex of the injury victims, and other factors, on the
      likelihood of hospitalization. The analysis focuses on consumer product injuries,
      and was based on approximately 400,000 injury cases reported through the U.S.
      Consumer Product Safety Commission's National Electronic Injury Surveillance
      System, a national probability sample of U.S. hospital emergency departments.
      Logistic regression was used to quantify the factors associated with the
      likelihood of hospitalization. The analysis suggests a smooth U-shaped
      relationship between the age of the victim and the likelihood of hospitalization,
      declining from about 3.4% for children under age 5 years to 1.9% for 15-24 year
      olds, but then rising to more than 25% for those ages 75 years and older. The
      likelihood of hospitalization was also significantly affected by the victim's
      sex, as well as by the types of products involved, fire involvement, and the size
      and type of hospital at which the injury was treated. This study shows that the
      probability of hospitalization is strongly correlated with the characteristics of
      those who are injured, as well as other factors. 

PMID- 23954688
TI  - Can we improve clinical prediction of at-risk older drivers?
AB  - OBJECTIVES: To conduct a pilot study to evaluate the predictive value of the
      Montreal Cognitive Assessment test (MoCA) and a brief test of multiple object
      tracking (MOT) relative to other tests of cognition and attention in identifying
      at-risk older drivers, and to determine which combination of tests provided the
      best overall prediction. METHODS: Forty-seven currently licensed drivers (58-95
      years), primarily from a clinical driving evaluation program, participated. Their
      performance was measured on: (1) a screening test battery, comprising MoCA, MOT,
      Mini-Mental State Examination (MMSE), Trail-Making Test, visual acuity, contrast
      sensitivity, and Useful Field of View (UFOV) and (2) a standardized road test.
      RESULTS: Eighteen participants were rated at-risk on the road test. UFOV subtest
      2 was the best single predictor with an area under the curve (AUC) of .84.
      Neither MoCA nor MOT was a better predictor of the at-risk outcome than either
      MMSE or UFOV, respectively. The best four-test combination (MMSE, UFOV subtest 2,
      visual acuity and contrast sensitivity) was able to identify at-risk drivers with
      95% specificity and 80% sensitivity (.91 AUC). CONCLUSIONS: Although the best
      four-test combination was much better than a single test in identifying at-risk
      drivers, there is still much work to do in this field to establish test batteries
      that have both high sensitivity and specificity.

PMID- 23954691
TI  - AAGL practice report: practice guidelines for laparoscopic subtotal/supracervical
      hysterectomy (LSH).
AB  - The first subtotal abdominal hysterectomy was described by Charles Clay in 1843,
      and the first laparoscopic subtotal hysterectomy (LSH) was described by Semm [1]
      in 1991. Whether to retain or remove the cervix remains controversial, with
      surgeons citing sexual satisfaction and prevention of pelvic organ prolapse as
      indicators for retention [2]. Because the only absolute indication for cervical
      removal is malignancy or its precursors, debate has continued as to the optimum
      surgical approach to hysterectomy for other indications. The evidence obtained
      from evaluating the effects of retaining the cervix, via any surgical approach,
      on sexual, urinary, and bowel function remains controversial [3-11]. The
      literature evaluating LSH is limited, and only 3 randomized controlled trials
      (RCTs), including 342 women, have reported psychologic outcomes, complications,
      and additional cervical procedures [4,12,13]. For the abdominal equivalent, there
      are 9 RCTs, including 1553 women, and a Cochrane review reported few important
      differences between the 2 approaches [8]. No such comparative data are available
      for LSH. This practice guideline will evaluate the evidence for LSH. This report
      was developed under the direction of the Practice Committee of the AAGL as a
      service to their members and other practicing clinicians.

PMID- 23954692
TI  - Efficacy of adipose tissue-mesenchymal stem cell transplantation in rats with
      acetaminophen liver injury.
AB  - OBJECTIVE: Acetaminophen intoxication is a leading cause of acute liver failure.
      Liver transplantation for acute liver failure is limited by the availability of
      donor organs. In this study, we aimed at identifying if the transplantation of
      adipose tissue-mesenchymal stem cells (ASCs) may exert therapeutic effects on
      acetaminophen-induced liver injury. METHODS: ASCs were isolated from human
      subcutaneous tissue and were transfected with a green fluorescent protein (GFP).
      Sprague-Dawley rats were administrated 300mg/kg of acetaminophen
      intraperitoneally and were transplanted with ASCs or vehicle. After 24h from
      acetaminophen administration, rats were sacrificed. Hepatic levels of
      isoprostanes, 8-hydroxyguanosine (8-OHG), nitrites/nitrates and reduced
      glutathione (GSH) were determined as markers of oxidative stress; JNK
      phosphorylation and hepatic levels of inflammatory cytokines and regeneration
      factors were also assessed. RESULTS: Transplantation of ASCs decreased AST, ALT
      and prothrombin time to the levels observed in control rats. Transplanted animals
      had normal plasma ammonia and did not display clinical encephalopathy. Liver
      sections of intoxicated rats treated with vehicle showed lobular necrosis and
      diffuse vacuolar degeneration; in rats transplanted with ASCs liver injury was
      almost absent. Transplantation of ASCs decreased liver isoprostanes, 8-OHG and
      nitrite-nitrates to the levels of control rats, while preserving GSH.
      Consistently, hepatic levels of TNF-alpha, MCP-1, IL-1beta, ICAM-1 and phospho
      JNK were markedly increased in rats treated with vehicle and were restored to the
      levels of controls in animals transplanted with ASCs. Furthermore, ASC
      transplantation increased liver expression of cyclin D1 and PCNA, two established
      hepatocyte regeneration factors, whereas ASCs were not able to metabolize
      acetaminophen in vitro. CONCLUSION: In this study, we demonstrated that ASC
      transplantation is effective in treating acetaminophen liver injury by enhancing
      hepatocyte regeneration and inhibiting liver stress and inflammatory signaling.

PMID- 23954693
TI  - Zfp819, a novel KRAB-zinc finger protein, interacts with KAP1 and functions in
      genomic integrity maintenance of mouse embryonic stem cells.
AB  - Pluripotency is maintained by both known and unknown transcriptional regulatory
      networks. In the present study, we have identified Zfp819, a KRAB-zinc finger
      protein, as a novel pluripotency-related factor and characterized its role in
      pluripotent stem cells. We show that Zfp819 is expressed highly in various types
      of pluripotent stem cells but not in their differentiated counterparts. We
      identified the presence of non-canonical nuclear localization signals in
      particular zinc finger motifs and identified them as responsible for the nuclear
      localization of Zfp819. Analysis of the Zfp819 promoter region revealed the
      presence of a transcriptionally active chromatin signature. Moreover, we
      confirmed the binding of pluripotency-related factors, Oct4, Sox2, and Nanog to
      the distal promoter region of Zfp819, indicating that the expression of this gene
      is regulated by a pluripotency transcription factor network. We found that the
      expression of endogenous retroviral elements (ERVs) such as Intracisternal A
      Particle (IAP) retrotransposons, Long Interspersed Nuclear Elements (LINE1), and
      Short Interspersed Nuclear Elements (SINE B1) is significantly upregulated in
      Zfp819-knockdown (Zfp819_KD) cells. In line with the activation of ERVs, we
      observed the occurrence of spontaneous DNA damage in Zfp819_KD cells.
      Furthermore, we tested whether Zfp819 can interact with KAP1, a KRAB-associated
      protein with a transcriptional repression function, and found the interaction
      between these two proteins in both in vitro and in vivo experiments. The
      challenging of Zfp819_KD cells with DNA damaging agent revealed that these cells
      are inefficient in repairing the damaged DNA, as cells showed presence of
      gammaH2A.X foci for a prolonged time. Collectively, our study identified Zfp819
      as a novel pluripotency-related factor and unveiled its function in genomic
      integrity maintenance mechanisms of mouse embryonic stem cells. 

PMID- 23954694
TI  - Identification of the STAT1 gene and the characterisation of its immune response
      to immunostimulants, including nervous necrosis virus (NNV) infection, in Malabar
      grouper (Epinephelus malabaricus).
AB  - Signal Transducer and Activator of Transcription (STAT)-1 is an indispensable
      signal transduction protein that is involved in the interferon pathway. STAT-1
      plays an important role in the innate immune response. The full-length cDNA of
      Malabar grouper (Epinephelus malabaricus) STAT-1, MgSTAT1, was cloned.
      Phylogenetic analysis was performed based on the amino acid sequence. Our results
      indicate that STAT1 is highly conserved with other vertebrates. We also report
      the expression of MgSTAT1 in different tissues treated with immune stimulants,
      including LPS, CpG ODN, and poly (I:C), in vivo. The expression of MgSTAT1 was
      significantly induced in the head kidney upon treatment with poly (I:C) compared
      to the control. Moreover, the results indicate that MgSTAT1 is up-regulated
      during nervous necrosis virus (NNV) infection. This study reveals that similar to
      the mammalian antiviral response, MgSTAT1 mediates the immune response in Malabar
      grouper. 

PMID- 23954695
TI  - Molecular characterization and expression analysis of three membrane-bound
      complement regulatory protein isoforms in the ginbuna crucian carp Carassius
      auratus langsdorfii.
AB  - Regulators of complement activation (RCA) play a role in protecting cells from
      excessive complement activation in humans. cDNA corresponding to three isoforms
      of teleost membrane-bound RCA protein (gTecrem) have been identified in the
      ginbuna crucian carp. gTecrem-1 consists of seven short consensus repeats (SCRs),
      whereas gTecrem-2 and gTecrem-3 have four SCRs. While gTecrem-1 possesses a
      tyrosine phosphorylation site in its cytoplasmic region, gTecrem-2 and gTecrem-3
      lack the site. Tissue distribution analysis showed that gTecrem-1 and gTecrem-2
      mRNAs were expressed in almost all tissues examined, whereas gTecrem-2 expression
      was not significantly detected in gill, liver, or intestine. Furthermore,
      analysis showed that gTecrem-1 was expressed in both peripheral blood leukocytes
      (PBLs) and erythrocytes and was also expressed in T cell subsets such as CD4(+),
      CD8(+) T cells, and IgM(+) B cells. gTecrem-2 expression was not detected in
      either PBLs or erythrocytes, whereas gTecrem-3 was expressed only in
      erythrocytes. These results suggested that gTecrem isoforms may serve different
      functional roles; gTecrem-1, which is expressed in T cells and possesses a
      tyrosine phosphorylation site, may act as a complement regulator and a cellular
      receptor in adaptive immunity. 

PMID- 23954696
TI  - Interplay between invertebrate C3a with vertebrate macrophages: functional
      characterization of immune activities of amphioxus C3a.
AB  - Our current knowledge of the structure and function of C3a comes from the study
      of vertebrate C3a anaphylatoxins, virtually nothing is known about the structure
      and function of C3a molecules in invertebrates. Here we demonstrated that C3a
      from the invertebrate chordate Branchiostoma japonicum, BjC3a, was similar to
      vertebrate C3a possessing potential antibacterial activity, as revealed by
      sequence analysis and computational modeling. The antibacterial activity of BjC3a
      was definitely confirmed by both antibacterial assay and TEM observation showing
      that recombinant BjC3a was directly bactericidal. Additionally, recombinant
      BjC3a, like vertebrate C3a, was capable of inducing sea bass macrophage migration
      and enhancing macrophage phagocytosis and respiratory burst response. Moreover,
      recombinant BjC3a-desArg (generated by removal of the C-terminal arginine), like
      mammalian C3a-desArg, retained the immunological activities of BjC3a such as
      antibacterial and respiratory burst-stimulating activities, indicating that the
      immunological functions of C3a-desArg were conserved throughout chordate
      evolution. Altogether, our findings show that invertebrate (amphioxus) BjC3a is
      able to interact with vertebrate (sea bass) macrophages and mediate immune
      activities, suggesting the emergence of the inflammatory pathway of the
      complement system similar to that of vertebrates in the basal chordate amphioxus.

PMID- 23954697
TI  - Apolipoprotein A1 in channel catfish: transcriptional analysis, antimicrobial
      activity, and efficacy as plasmid DNA immunostimulant against Aeromonas
      hydrophila infection.
AB  - The objectives of this study were to: 1) determine transcriptional profiles of
      apolipoprotein A1 (ApoA1) in collected channel catfish tissues after infection
      with Aeromonas hydrophila by bath immersion; 2) investigate whether recombinant
      channel catfish apolipoprotein A1 produced in Escherichia coli expression system
      possesses any antimicrobial activity against A. hydrophila; 3) evaulate whether
      recombinant channel catfish apolipoprotein A1 plasmid DNA could be used as
      immunostimulant to protect fish against A. hydrophila infection. Quantitative PCR
      revealed that the transcription levels of ApoA1 in infected catfish were
      significantly (P < 0.05) more induced in the anterior kidney. Recombinant apoA1
      produced in E. coli expression system exhibited lytic activity against Gram
      positive Micrococcus lysodeikticus and Gram-negative A. hydrophila. When pcDNA3.2
      vectored recombinant apoA1 was transfected in channel catfish gill cells G1B, the
      over-expression of pcDNA-ApoA1 offered significant (P < 0.05) protection to G1B
      cells against A. hydrophila infection. When channel catfish were
      intraperitoneally injected with QCDCR adjuvant formulated pcDNA-ApoA1 and
      challenged with a highly virulent A. hydrophila strain AL-09-71 at two days post
      injection, pcDNA-ApoA1 injection offered 100% protection to channel catfish.
      Macrophages of fish injected with pcDNA-ApoA1 produced significantly (P < 0.05)
      higher amounts of reactive oxygen species and nitric oxide than that of fish
      injected with pcDNA vector alone. Our results suggest that pcDNA-ApoA1 could be
      used as a novel immunostimulant to offer immediate protection to catfish against
      A. hydrophila infection. 

PMID- 23954698
TI  - Effects of praziquantel and sanguinarine on expression of immune genes and
      susceptibility to Aeromonas hydrophila in goldfish (Carassius auratus) infected
      with Dactylogyrus intermedius.
AB  - Praziquantel and sanguinarine have been demonstrated positive therapeutic effects
      on monogenean Dactylogyrus intermedius; however, few studies have considered the
      post impacts of these antiparasitic chemicals on host after repelling the
      parasites. The changes of expression of selected immune genes (CCL-1, CXCL-8, IL
      1beta-1, IL-1beta-2, TNFalpha-1, TNFalpha-2 and TGF-beta) in gill, kidney and
      spleen and bacterial loads of Aeromonas hydrophila in gill, kidney, spleen and
      liver following bath administration of these antiparasitic chemicals were
      evaluated. The results showed that praziquantel and sanguinarine up-regulated to
      varying degrees of CXCL-8, IL-1beta-1, IL-1beta-2, TNFalpha-1 and TNFalpha-2 in
      gill, kidney and spleen. They both decreased the CCL-1 expression in gill while
      increased it in kidney and spleen. However, in all the tested tissues, the
      expression of TGF-beta decreased in praziquantel treated goldfish whereas that
      increased in sanguinarine treated goldfish. The A. hydrophila challenge test
      showed that the praziquantel treatment enhanced the susceptibility to A.
      hydrophila while sanguinarine treatment decreased the susceptibility, as compared
      with the non-treated group. Overall, the results indicate that bath
      administration of praziquantel and sanguinarine modulates the immune related
      genes in goldfish and these may, to some extent, affect their ability to resist
      bacterial pathogens. 

PMID- 23954699
TI  - Osteoimmunology in mucopolysaccharidoses type I, II, VI and VII. Immunological
      regulation of the osteoarticular system in the course of metabolic inflammation.
AB  - BACKGROUND: Mucopolysaccharidoses (MPSs) are rare genetic diseases caused by a
      deficient activity of one of the lysosomal enzymes involved in the
      glycosaminoglycan (GAG) breakdown pathway. These metabolic blocks lead to the
      accumulation of GAGs in various organs and tissues, resulting in a multisystemic
      clinical picture. The pathological GAG accumulation begins a cascade of
      interrelated responses: metabolic, inflammatory and immunological with systemic
      effects. Metabolic inflammation, secondary to GAG storage, is a significant cause
      of osteoarticular symptoms in MPS disorders. OBJECTIVE AND METHOD: The aim of
      this review is to present recent progress in the understanding of the role of
      inflammatory and immune processes in the pathophysiology of osteoarticular
      symptoms in MPS disorders and potential therapeutic interventions based on
      published reports in MPS patients and studies in animal models. RESULTS AND
      CONCLUSIONS: The immune and skeletal systems have a number of shared regulatory
      molecules and many relationships between bone disorders and aberrant immune
      responses in MPS can be explained by osteoimmunology. The treatment options
      currently available are not sufficiently effective in the prevention, inhibition
      and treatment of osteoarticular symptoms in MPS disease. A lot can be learnt from
      interactions between skeletal and immune systems in autoimmune diseases such as
      rheumatoid arthritis (RA) and similarities between RA and MPS point to the
      possibility of using the experience with RA in the treatment of MPS in the
      future. The use of different anti-inflammatory drugs requires further study, but
      it seems to be an important direction for new therapeutic options for MPS
      patients.

PMID- 23954700
TI  - Subsets of symptomatic hand osteoarthritis in community-dwelling older adults in
      the United Kingdom: prevalence, inter-relationships, risk factor profiles and
      clinical characteristics at baseline and 3-years.
AB  - OBJECTIVE: To compare the population prevalence, inter-relationships, risk factor
      profiles and clinical characteristics of subsets of symptomatic hand
      osteoarthritis (OA) with a view to understanding their relative frequency and
      distinctiveness. METHOD: 1076 community-dwelling adults with hand symptoms (60%
      women, mean age 64.7 years) were recruited and classified into pre-defined
      subsets using physical examination and standardised hand radiographs, scored with
      the Kellgren & Lawrence (K&L) and Verbruggen-Veys grading systems. Detailed
      information on selected risk factors was obtained from direct measurement (Body
      Mass Index (BMI)), self-complete questionnaires (excessive use of hands, previous
      hand injury) and medical record review (hypertension, dyslipidaemia, type 2
      diabetes). Hand pain and disability were self-reported at baseline and 3-year
      follow-up using Australian/Canadian Osteoarthritis Hand Index (AUSCAN). RESULTS:
      Crude population prevalence estimates for symptomatic hand OA subsets in the
      adult population aged 50 years and over were: thumb base OA (22.4%), nodal
      interphalangeal joint (IPJ) OA (15.5%), generalised hand OA (10.4%), non-nodal
      IPJ OA (4.9%), erosive OA (1.0%). Apart from thumb base OA, there was
      considerable overlap between the subsets. Erosive OA appeared the most
      distinctive with the highest female: male ratio, and the most disability at
      baseline and 3-years. A higher frequency of obesity, hypertension, dyslipidaemia,
      and metabolic syndrome was observed in this subset. CONCLUSION: Overlap in the
      occurrence of hand OA subsets poses conceptual and practical challenges to the
      pursuit of distinct phenotypes. Erosive OA may nevertheless provide particular
      insight into the role of metabolic and cardiovascular risk factors in the
      pathogenesis of OA.

PMID- 23954701
TI  - Interleukin 6 mediates selected effects of Notch in chondrocytes.
AB  - OBJECTIVE: Notch receptors determine cell fate by regulating transcription, an
      event mediated by the Notch intracellular domain (NICD), which is generated by
      proteolysis brought about by Notch-ligand interactions. Since Notch activation or
      exposure to interleukin (Il)6 have similar effects in chondrocytes, we explored
      whether interleukin 6 (Il6) contributes to the mechanisms of Notch action in
      these cells. METHOD: NICD was overexpressed in primary chondrocytes from
      Rosa(Notch) mice, where the Rosa26 promoter precedes a loxP-flanked STOP cassette
      followed by the NICD coding sequence. Cells were infected with adenoviral vectors
      expressing Cre to induce NICD or green fluorescent protein (GFP) as control. Gene
      expression was determined by quantitative reverse transcription-polymerase chain
      reaction (qRT-PCR). Il6 protein concentration in the culture media was determined
      by enzyme-linked immunosorbent assay (ELISA). To test the mechanisms of Notch
      action on Il6 expression, cells were transfected with a fragment of the Il6
      promoter or control vector pGL3, or transcriptionally arrested with 5,6-dichloro
      1-beta-d-ribofuranosylbenzimidazole. Il6 was inhibited with a neutralizing
      antibody, whereas a normal immunoglobulin G (IgG) was used as control. RESULTS:
      NICD induced Il6 mRNA and protein, and transactivated the Il6 promoter without
      affecting Il6 mRNA stability. Il6 neutralization had no impact on gene expression
      under basal conditions, and did not modify the effects of NICD on sex determining
      region-Y-related high mobility group-box gene (Sox)9, collagen type II alpha1
      (Col2a1) and collagen type X alpha1 (Col10a1) expression. Conversely, Il6
      neutralization opposed aggrecan (Acan) suppression and prevented matrix
      metalloprotease (Mmp)13 induction by NICD. CONCLUSION: Il6 mediates suppression
      of Acan and induction of Mmp13 expression by Notch in chondrocytes.

PMID- 23954702
TI  - Osteoarthritis year 2013 in review: biomarkers; reflecting before moving forward,
      one step at a time.
AB  - In 2010, in Osteoarthritis and Cartilage, we published a comprehensive systematic
      review applying the consensus BIPED criteria (Burden of Disease, Investigative,
      Prognostic, Efficacy of Intervention and Diagnostic) criteria on serum and
      urinary biochemical markers for knee and hip osteoarthritis (OA) using
      publications that were available at that time. It appeared that none of the
      biochemical markers at that time were sufficiently discriminating to allow
      diagnosis and prognosis of OA in individual or limited numbers of patients, nor
      performed so consistently that they could function as primary outcome parameters
      in clinical trials. Also at present, almost 3 years later, this ultimate goal has
      not been reached (yet). Frankly, it might be questioned whether we are making the
      most adequate steps ahead and maybe we have to take a step back to reconsider our
      approaches. Some reflections are made and discussed: A critical review of
      molecular metabolism in OA and validation of currently investigated marker
      molecules in this may be vital and may lead to new and better markers. Creating
      cohorts in which synovial fluid (SF) is obtained in a systematic way, together
      with serum and urine, may also bring the field a further step ahead. Thirdly,
      better understanding of different phenotypes (subtypes) of OA may facilitate
      identification and validation of biochemical markers. Finally, the systems
      biology approach as discussed in the last years OA in review on biomarkers,
      although very complex, might provide steps forward. Looking ahead, we are
      optimistic but realistic in our expectations, we believe that the field can be
      brought forward by critically and cautiously reconsidering our approaches, and
      making changes forward, one step at a time. 

PMID- 23954703
TI  - Development of a fully automatic shape model matching (FASMM) system to derive
      statistical shape models from radiographs: application to the accurate capture
      and global representation of proximal femur shape.
AB  - OBJECTIVE: To evaluate the accuracy and sensitivity of a fully automatic shape
      model matching (FASMM) system to derive statistical shape models (SSMs) of the
      proximal femur from non-standardised anteroposterior (AP) pelvic radiographs.
      DESIGN: AP pelvic radiographs obtained with informed consent and appropriate
      ethical approval were available for 1105 subjects with unilateral hip
      osteoarthritis (OA) who had been recruited previously for The arcOGEN Study. The
      FASMM system was applied to capture the shape of the unaffected (i.e., without
      signs of radiographic OA) proximal femur from these radiographs. The accuracy and
      sensitivity of the FASMM system in calculating geometric measurements of the
      proximal femur and in shape representation were evaluated relative to validated
      manual methods. RESULTS: De novo application of the FASMM system had a mean point
      to-curve error of less than 0.9 mm in 99% of images (n = 266). Geometric
      measurements generated by the FASMM system were as accurate as those obtained
      manually. The analysis of the SSMs generated by the FASMM system for male and
      female subject groups identified more significant differences (in five of 17 SSM
      modes after Bonferroni adjustment) in their global proximal femur shape than
      those obtained from the analysis of conventional geometric measurements.
      Multivariate gender-classification accuracy was higher when using SSM mode values
      (76.3%) than when using conventional hip geometric measurements (71.8%).
      CONCLUSIONS: The FASMM system rapidly and accurately generates a global SSM of
      the proximal femur from radiographs of varying quality and resolution. This
      system will facilitate complex morphometric analysis of global shape variation
      across large datasets. The FASMM system could be adapted to generate SSMs from
      the radiographs of other skeletal structures such as the hand, knee or pelvis.

PMID- 23954704
TI  - Sustained clinical and structural benefit after joint distraction in the
      treatment of severe knee osteoarthritis.
AB  - BACKGROUND: Treatment of severe osteoarthritis (OA) in relatively young patients
      is challenging. Although successful, total knee prosthesis has a limited
      lifespan, with the risk of revision surgery, especially in active young patients.
      Knee joint distraction (KJD) provides clinical benefit and tissue structure
      modification at 1-year follow-up. The present study evaluates whether this
      benefit is preserved during the second year of follow-up. METHODS: Patients
      included in this study presented with end-stage knee OA and an indication for
      total knee replacement (TKR); they were less than 60 years old with a VAS pain
      >=60 mm (n = 20). KJD was applied for 2 months (range 54-64 days) and clinical
      parameters assessed using the WOMAC questionnaire and VAS pain score. Changes in
      cartilage structure were measured using quantitative MRI, radiography, and
      biochemical analyses of collagen type II turnover (ELISA). RESULTS: Average
      follow-up was 24 (range 23-25) months. Clinical improvement compared with
      baseline (BL) was observed at 2-year follow-up: WOMAC improved by 74% (P < 0.001)
      and VAS pain decreased by 61% (P < 0.001). Cartilage thickness observed by MRI
      (2.35 mm (95%CI, 2.06-2.65) at BL) was significantly greater at 2-year follow-up
      (2.78 mm (2.50-3.09); P = 0.03). Radiographic minimum joint space width (JSW)
      (1.1 mm (0.5-1.7) at BL) was significantly increased at 2-year follow-up as well
      (1.7 mm (1.1-2.3); P = 0.03). The denuded area of subchondral bone visualized by
      MRI (22% (95%CI, 12.5-31.5) at BL) was significantly decreased at 2-year follow
      up (8% (3.6-12.2); P = 0.004). The ratio of collagen type II synthesis over
      breakdown was increased at 2-year follow-up (P = 0.07). CONCLUSION: Clinical
      improvement by KJD treatment is sustained for at least 2 years. Cartilage repair
      is still present after 2 years (MRI) and the newly formed tissue continues to be
      mechanically resilient as shown by an increased JSW under weight-bearing
      conditions.

PMID- 23954706
TI  - Band smearing of PCR amplified bacterial 16S rRNA genes: dependence on initial
      PCR target diversity.
AB  - Band smearing in agarose gels of PCR amplified bacterial 16S rRNA genes is
      understood to comprise amplicons of varying sizes arising from PCR errors, and
      requires elimination. We consider that with amplified heterogeneous DNA, delayed
      electro-migration is caused not by PCR errors but by dsDNA structures that arise
      from imperfect strand pairing. The extent of band smearing was found to be
      proportional to the sequence heterogeneity in 16S rRNA variable regions.
      Denaturing alkaline gels showed that all amplified DNA was of the correct size. A
      novel bioinformatic approach was used to reveal that band smearing occurred due
      to imperfectly paired strands of the amplified DNA. Since the smear is a
      structural fraction of the correct size PCR product, it carries important
      information on richness and diversity of the target DNA. For accurate analysis,
      the origin of the smear must first be identified before it is eliminated by
      examining the amplified DNA in denaturing alkaline gels. 

PMID- 23954705
TI  - MALDI-MS tissue imaging identification of biliverdin reductase B overexpression
      in prostate cancer.
AB  - New biomarkers are needed to improve the specificity of prostate cancer detection
      and characterisation of individual tumors. In a proteomics profiling approach
      using MALDI-MS tissue imaging on frozen tissue sections, we identified
      discriminating masses. Imaging analysis of cancer, non-malignant benign
      epithelium and stromal areas of 15 prostatectomy specimens in a test and 10 in a
      validation set identified characteristic m/z peaks for each tissue type, e.g. m/z
      10775 for benign epithelial, m/z 6284 and m/z 6657.5 for cancer and m/z 4965 for
      stromal tissue. A 10-fold cross-validation analysis showed highest discriminatory
      ability to separate tissue types for m/z 6284 and m/z 6657.5, both overexpressed
      in cancer, and a multicomponent mass peak cluster at m/z 10775-10797.4
      overexpressed in benign epithelial tissue. ROC AUC values for these three masses
      ranged from 0.85 to 0.95 in the discrimination of malignant and non-malignant
      tissue. To identify the underlying proteins, prostate whole tissue extract was
      separated by nano-HPLC and subjected to MALDI TOF/TOF analysis. Proteins in
      fractions containing discriminatory m/z masses were identified by MS/MS analysis
      and candidate marker proteins subsequently validated by immunohistochemistry
      (IHC). Biliverdin reductase B (BLVRB) turned out to be overexpressed in PCa
      tissue. BIOLOGICAL SIGNIFICANCE: In this study on cryosections of radical
      prostatectomies of prostate cancer patients, we performed a MALDI-MS tissue
      imaging analysis and a consecutive protein identification of significant m/z
      masses by nano-HPLC, MALDI TOF/TOF and MS/MS analysis. We identified BLVRB as a
      potential biomarker in the discrimination of PCa and benign tissue, also
      suggesting BVR as a feasible therapeutic target.

PMID- 23954707
TI  - Defining and characterizing drug/compound function.
AB  - The receptor concept, now more than century old, remains the core concept in
      understanding the mechanisms of disease causality and drug action. Originally
      formulated in the early 1900s, receptor theory has evolved in both detail and
      complexity as the tools of molecular biology and increasingly sophisticated
      research technologies have facilitated the study of drug/ligand receptor
      interactions at the molecular level. The result has been a more detailed and
      nuanced understanding of the parameters of drug action that together with
      knowledge of the pleotropic nature of cellular targets and associated signaling
      pathways has reshaped the receptor concept. Added to the basic agonist/antagonist
      view of drug/ligand function, concepts like allosterism, inverse agonism, biased
      signaling and compound residence time have provided a broader understanding of
      compound-target interactions to better inform drug discovery efforts. The
      iteration of descriptive data from pharmacological experiments to provide generic
      indices of affinity and efficacy can now be used to predict expected
      drug/compound effects in other cell/organ systems where the sensitivity of the
      latter to drug effects (either via expression levels of cell surface receptors or
      variances in the efficiency with which those receptors are coupled to cytosolic
      metabolic processes) can be accommodated. 

PMID- 23954708
TI  - Animal models of human disease: challenges in enabling translation.
AB  - Animal models have historically played a critical role in the exploration and
      characterization of disease pathophysiology, target identification, and in the in
      vivo evaluation of novel therapeutic agents and treatments. In the wake of
      numerous clinical trial failures of new chemical entities (NCEs) with promising
      preclinical profiles, animal models in all therapeutic areas have been
      increasingly criticized for their limited ability to predict NCE efficacy, safety
      and toxicity in humans. The present review discusses some of the challenges
      associated with the evaluation and predictive validation of animal models, as
      well as methodological flaws in both preclinical and clinical study designs that
      may contribute to the current translational failure rate. The testing of disease
      hypotheses and NCEs in multiple disease models necessitates evaluation of
      pharmacokinetic/pharmacodynamic (PK/PD) relationships and the earlier development
      of validated disease-associated biomarkers to assess target engagement and NCE
      efficacy. Additionally, the transparent integration of efficacy and safety data
      derived from animal models into the hierarchical data sets generated
      preclinically is essential in order to derive a level of predictive utility
      consistent with the degree of validation and inherent limitations of current
      animal models. The predictive value of an animal model is thus only as useful as
      the context in which it is interpreted. Finally, rather than dismissing animal
      models as not very useful in the drug discovery process, additional resources,
      like those successfully used in the preclinical PK assessment used for the
      selection of lead NCEs, must be focused on improving existing and developing new
      animal models. 

PMID- 23954709
TI  - Basal ganglia serotonin 1B receptors in parkinsonian monkeys with L-DOPA-induced
      dyskinesia.
AB  - L-DOPA-induced dyskinesias (LID)s are abnormal involuntary movements limiting the
      chronic use of L-DOPA, the main pharmacological treatment of Parkinson's disease
      (PD). Serotonin receptors are thought to contribute to LID but serotonin 1B (5
      HT1B) receptors have never been investigated in any primate models of PD and LID.
      Therefore, we measured 5-HT1B receptors with [(3)H]GR 125743 autoradiography in
      controls, MPTP-lesioned monkeys, and L-DOPA-treated MPTP monkeys, with or without
      Ro 61-8048 treatment, a kynurenine hydroxylase inhibitor alleviating LID. In
      normal condition, 5-HT1B receptor specific binding was highest in the substantia
      nigra pars reticulata (SNr), high in the globus pallidus (GP), nucleus accumbens
      and substantia innominata and lower in the caudate nucleus and putamen. 5-HT1B
      receptors were increased in caudate nucleus, putamen and SNr of MPTP monkeys
      compared to controls. L-DOPA-treated MPTP monkeys had elevated 5-HT1B receptor
      specific binding in caudate nucleus, putamen, SNr and internal GP. In all these
      brain regions, increases were prevented by co-administration of Ro 61-8048. No
      effect of MPTP lesion or treatment was observed for 5-HT1B specific binding in
      the external GP, nucleus accumbens and substantia innominata. This study is the
      first description in primates of altered brain 5-HT1B receptors associated with
      prevention of LID. 

PMID- 23954711
TI  - Relationship between plasma mid-regional pro-adrenomedullin level and resistance
      to antihypertensive therapy in stable kidney transplant recipients.
AB  - We investigated the relationship between plasma mid-regional pro-adrenomedullin
      (MR-proADM)-like immunoreactive substance (IS) level and clinical characteristics
      associated with renal failure or resistance to antihypertensive therapy in stable
      kidney transplant recipients. Forty-six Japanese kidney transplant recipients who
      underwent transplantation more than 90 days prior to the study were included. To
      evaluate resistance to antihypertensive therapy, we calculated the treatment
      intensity score of the antihypertensive drugs in each recipient. Morning blood
      samples were collected and plasma MR-proADM-IS levels were measured using an
      enzyme immunoassay. A significant correlation was observed between plasma MR
      proADM-IS level with creatinine clearance or treatment intensity score. Multiple
      regression analysis identified plasma MR-proADM level and body mass index as
      significant independent factors associated with treatment intensity score. Plasma
      MR-proADM level may be a useful biomarker indicating the degree of resistance to
      antihypertensive therapy.

PMID- 23954710
TI  - Comparison of transduction efficiency among various lentiviruses containing GFP
      reporter in bone marrow hematopoietic stem cell transplantation.
AB  - HIV-derived lentiviral vectors have been used widely to transduce non-dividing
      cells, such as hematopoietic stem cells (HSCs), in the setting of gene therapy.
      In this study, we screened lentiviral vectors for their ability to drive
      expression of the murine MHC class II chaperone, invariant chain (Ii) and a GFP
      reporter. The vectors included T2A vector with T2A-separated Ii and GFP under the
      same MSCV promoter, dual-promoter vectors with separate promoters for Ii and GFP
      (called MSCV or EF1a according to the promoter driving Ii expression), and a
      vector with EF1a driving a fusion of Ii/GFP (called Fusion vector). T2A and MSCV
      induced the highest levels of Ii and GFP expression, respectively, after direct
      transfection of 293T cells. All vectors except the Fusion vector drove expression
      of functional Ii, based on the enhancement of MHC class II level, which is a
      known consequence of Ii expression. Comparing the vectors after they were
      packaged into lentiviruses and used to transduce 293T, we found that MSCV and
      EF1a vectors mediated higher Ii and GFP expression. In ckit(+) bone marrow (BM)
      cells, MSCV still induced the highest Ii and GFP expression, whereas EF1a induced
      only robust Ii expression. Regardless of the vector, both Ii and GFP levels were
      significantly reduced in BM cells compared to 293T cells. When in vivo expression
      was assessed in cells derived from MSCV-transduced BM-HSCs, up to 80% of myeloid
      cells were GFP(+), but no Ii expression was observed. In contrast,
      transplantation of EF1a-transduced BM-HSCs led to much higher in vivo Ii
      expression. Thus, among those compared, dual-promoter vector-based lentivirus
      with the EF1a promoter driving the gene of interest is optimal for murine BM-HSC
      transduction.

PMID- 23954712
TI  - Release of biologically active kinin peptides, Met-Lys-bradykinin and Leu-Met-Lys
      bradykinin from human kininogens by two major secreted aspartic proteases of
      Candida parapsilosis.
AB  - In terms of infection incidence, the yeast Candida parapsilosis is the second
      after Candida albicans as causative agent of candidiases in humans. The major
      virulence factors of C. parapsilosis are secreted aspartic proteases (SAPPs)
      which help the pathogen to disseminate, acquire nutrients and dysregulate the
      mechanisms of innate immunity of the host. In the current work we characterized
      the action of two major extracellular proteases of C. parapsilosis, SAPP1 and
      SAPP2, on human kininogens, proteinaceous precursors of vasoactive and
      proinflammatory bradykinin-related peptides, collectively called the kinins. The
      kininogens, preferably the form with lower molecular mass, were effectively
      cleaved by SAPPs, with the release of two uncommon kinins, Met-Lys-bradykinin and
      Leu-Met-Lys-bradykinin. While optimal at acidic pH (4-5), the kinin release yield
      was only 2-3-fold lower at neutral pH. These peptides were able to interact with
      cellular kinin receptors of B2 subtype and to stimulate the human endothelial
      cells HMEC-1 to increased secretion of proinflammatory interleukins (ILs), IL
      1beta and IL-6. The analysis of the stability of SAPP-generated kinins in plasma
      suggested that they are biologically equivalent to bradykinin, the best agonist
      of B2 receptor subtype and can be quickly converted to des-Arg(9)-bradykinin, the
      agonist of inflammation-inducible B1 receptors.

PMID- 23954713
TI  - Molecular cloning, characterization and recombinant expression of crustacean
      hyperglycemic hormone in white shrimp Litopenaeus vannamei.
AB  - Crustacean hyperglycemic hormone (CHH) plays an important role in crustacean. In
      the present study, a full-length cDNA of CHH was cloned from the eyestalk of
      Litopenaeus vannamei by RACE approach for the first time. The full-length cDNA of
      LvCHH was 846 bp, containing a 5' untranslated region (UTR) of 65 bp, a 3' UTR of
      436 bp with a canonical polyadenylation signal-sequence AATAA and a poly (A)
      tail, and an open reading frame (ORF) of 345 bp. The ORF encoded a polypeptide of
      114 amino acids including a 24 amino acid signal peptide. The calculated
      molecular mass of the mature protein (74 amino acids) was 8.76 kDa with an
      estimated pI of 6.78. The sequence of LvCHH was submitted in NCBI GenBank under
      the accession number HM748790.2. Phylogenetic analysis revealed that LvCHH was
      clustered with CHH of other crustaceans. Tissue distribution analysis revealed
      that the expression of LvCHH mRNA was observed in all tissues but gill, and was
      highest in heart. Specific primers containing Xho I and BamH I restriction sites
      respectively, were designed based on the obtained ORF sequence of LvCHH gene and
      the cloning sites of expression vector pET-32a (+). The recombinant plasmid LvCHH
      pET32a, was used to transform Escherichia coli BL21 (DE3). LvCHH was successfully
      expressed by means of SDS-PAGE and western blot analysis. We detected gill
      Na(+)/K(+)-ATPase activity after rLvCHH protein injection and found that All the
      experimental group Na(+)/K(+)-ATPase activity presented peak change among 0-6h,
      and the peaks of all treated groups occurred in 1 h. 20 and 30 MUg/shrimp(-1)
      groups showed significant increase (P<0.05) in 1h post-injection. L. vannamei
      were exposed for 96h to hypo- and hyper-salinity challenge. Hypo-salinity caused
      a significant rise (P<0.05) in the mRNA expression of CHH and gill Na(+)/K(+)
      ATPase activity at 12h and 24h respectively, then the CHH mRNA expression
      declining by 24h, and returned to control group level by 48 h, and the Na(+)/K(+)
      ATPase activity tended to be stable after 72 h, and higher than that of control.
      The hyper-salinity challenge had the same trend at mRNA expression with the hypo
      salinity group. The Na(+)/K(+)-ATPase activity had no significant change under
      the low salinity challenge. All these results indicate that LvCHH is an important
      hormone involved in the osmosis responses of swimming shrimps, and can provide
      further information of crustacean osmoregulation physiological mechanism.

PMID- 23954714
TI  - The role of posterior parietal cortices on prismatic adaptation effects on the
      representation of time intervals.
AB  - Previous studies provided evidence of an ascending left-to-right spatial
      representation of time durations by using a technique affecting high levels of
      spatial cognition, i.e. prismatic adaptation (PA). Indeed, PA that induced a
      leftward aftereffect distorted time representation toward an underestimation,
      while PA that induced a rightward aftereffect distorted time representation
      toward an overestimation. The present study advances previous findings on the
      effects of PA on time by investigating the neural basis subtending these effects.
      We focused on the posterior parietal cortex (PPC) since it is involved in the PA
      procedure and also in the formulation of the spatial representation of time. We
      conducted two experiments where right-handed healthy adults were submitted to a
      time task, before and after PA, that could induce a leftward or rightward
      aftereffect. Repetitive TMS (rTMS) was used to inhibit the left or right PPC
      before PA administration. In a first experiment the time task consisted of
      reproducing an half duration (time bisection task) by pressing a key and the
      participants responded and adapted to prisms with their right hand. In a second
      experiment the time task consisted of reproducing a whole duration (time
      reproduction task) by pressing a key and the participants responded and adapted
      to prisms with their left hand. We found an abolition of the effects of PA on
      time when rTMS was delivered on the left and not on the right PPC, regardless of
      the task and moreover, when the participants responded and adapted with the right
      hand and also with the left hand. This result suggests a direct involvement of
      the left PPC in the interactive process, between spatial modulations induced by
      PA and the spatial representation of time, that does not depend on motor
      processes. This study provides useful results for future investigations on the
      neural mechanisms subtending the effects of PA on spatial representations. 

PMID- 23954715
TI  - Autobiographical memory in semantic dementia: new insights from two patients
      using fMRI.
AB  - Episodic autobiographical memory (EAM) consists of personal events embedded
      within a specific spatiotemporal context. Patients with semantic dementia (SD)
      generally show preserved recent EAMs, but a controversy remains concerning their
      ability to retrieve remote ones. Only one fMRI study examined remote
      autobiographical memory in SD through a longitudinal case study (Maguire,
      Kumaran, Hassabis, & Kopelman, 2010). Here, we propose a cross-sectional study to
      test the hippocampo-neocortical up-regulation hypothesis, through a multimodal
      approach (gray matter volume, activation, connectivity analyses), directly
      comparing recent and remote autobiographical memory retrieval and collecting data
      to asses phenomelogical re-experiencing. EAM retrieval recruits a distributed
      network of brain regions, notably the hippocampus which is shown to be atrophied
      in SD, although some studies report no hippocampal atrophy in SD. Using fMRI, we
      examined recent and remote EAM retrieval in two SD patients with different
      profiles of hippocampal atrophy, compared to 12 healthy elders (HE). JPL
      presented severe bilateral hippocampal atrophy, while EP showed sparing of both
      hippocampi. Behaviourally, JPL was impaired at retrieving EAMs from both life
      periods and showed poorer use of visual mental imagery than HE, while EP
      retrieved memories which were as episodic as those of HE for both periods and
      relied on greater use of visual mental imagery than HE. Neuroimaging results
      showed that, for JPL, hyperactivations of the residual hippocampal tissue and of
      frontal, lateral temporal, occipital and parietal cortices did not efficiently
      compensate his autobiographical memory deficit. EP however presented
      hyperactivations in similar neocortical regions which appeared to be more
      efficient in compensating for atrophy elsewhere, since EP's EAM retrieval was
      preserved. Functional connectivity analyses focusing on the hippocampus showed
      how the residual hippocampal activity was connected to other brain areas. For
      JPL, recent autobiographical retrieval was associated with connectivity between
      the posterior hippocampus and middle occipital gyrus, while for EP, connectivity
      was detected between the anterior hippocampus and numerous regions (medial
      temporal, occipital, temporal, frontal, parietal) for both recent and remote
      periods. These findings suggest that intensification of hippocampal atrophy in SD
      strongly affects both recent and remote autobiographical recollection. Up
      regulation of neocortical regions and functional hippocampal-neocortical
      connectivity within the autobiographical network may be insufficient to
      compensate the lifelong episodic memory deficit for patients with extensive
      hippocampal atrophy. 

PMID- 23954716
TI  - Bioremediation of reject water from anaerobically digested waste water sludge
      with macroalgae (Ulva lactuca, Chlorophyta).
AB  - Phosphorus and biologically active nitrogen are valuable nutrient resources.
      Bioremediation with macroalgae is a potential means for recovering nutrients from
      waste streams. In this study, reject water from anaerobically digested sewage
      sludge was successfully tested as nutrient source for cultivation of the green
      macroalgae Ulva lactuca. Maximal growth rates of 54.57+/-2.16% FW d(-1) were
      achieved at reject water concentrations equivalent to 50 MUM NH4(+). Based on the
      results, the growth and nutrient removal was parameterised as function of NH4(+)
      concentration a tool for optimisation of any similar phycoremediation system.
      Maximal nutrient removal rates of 22.7 mg N g DW(-1) d(-1) and 2.7 mg P g DW(-1)
      d(-1) were achieved at reject water concentrations equivalent to 80 and 89 MUM
      NH4(+), respectively. A combined and integrated use of the produced biomass in a
      biorefinery is thought to improve the feasibility of using Ulva for
      bioremediation of reject water.

PMID- 23954717
TI  - Removal of dimethyl sulfide by the combination of non-thermal plasma and
      biological process.
AB  - A bench scale system integrated with a non-thermal plasma (NTP) and a biotricking
      filtration (BTF) unit for the treatment of gases containing dimethyl sulfide
      (DMS) was investigated. DMS removal efficiency in the integrated system was up to
      96%. Bacterial communities in the BTF were assessed by PCR-DGGE, which play the
      dominant role in the biological processes of metabolism, sulfur oxidation,
      sulfate-reducing and carbon oxidation. The addition of ozone from NTP made
      microbial community in BTF more complicated and active for DMS removal. The NTP
      oxidize DMS to simple compounds such as methanol and carbonyl sulfide; the
      intermediate organic products and DMS are further oxidized to sulfate, carbon
      dioxide, water vapors by biological degradation. These results show that NTP-BTF
      is achievable and open new possibilities for applying the integrated with NTP and
      BTF to odour gas treatment. 

PMID- 23954718
TI  - Preparation and characterization of a hierarchical porous char from sewage sludge
      with superior adsorption capacity for toluene by a new two-step pore-fabricating
      process.
AB  - A kind of hierarchical porous char (SCCA/Zn) was prepared from sewage sludge by a
      new two-step pore-fabricating process coupling citric acid (CA) with ZnCl2 in a
      pyrolysis process. The char was characterized by element analysis, N2-adsorption
      and mercury intrusion measurement etc. It is found that coupling CA and ZnCl2 can
      synergistically fabricate pores in the pyrolysis process, resulting in a
      hierarchical porous char, SCCA/Zn, with the largest SBET of 867.6 m(2) g(-1) due
      to the fact that the former contributes to the fabrication of macro-pores, which
      provides more space for fabricating meso- and micro-pores by ZnCl2 activation.
      Although the SBET of SCCA/Zn was 15% less than that of activated carbon fiber
      (ACF, SBET=999.5 m(2) g(-1)), SCCA/Zn had a higher toluene adsorption capacity
      (0.83 g g(-1)) than ACF. The inconsistence between their SBET and adsorption
      capacity can be ascribed to the strong hydrophobic property of SCCA/Zn.

PMID- 23954719
TI  - Triterpene saponosides from Lysimachia ciliata differentially attenuate invasive
      potential of prostate cancer cells.
AB  - Neither androgen ablation nor chemotherapeutic agents are effective in reducing
      the risk of prostate cancer progression. On the other hand, multifaceted effects
      of phytochemicals, such as triterpene saponins, on cancer cells have been
      suggested. A promising safety and tolerability profile indicate their possible
      application in the treatment of advanced prostate cancers. We analyzed the
      specificity, selectivity and versatility of desglucoanagalloside B effects on
      human prostate cancer cells derived from prostate cancer metastases to brain (DU
      145 cells) and bone (PC-3 cells). Prominent growth arrest and apoptotic response
      of both cell types was observed in the presence of sub-micromolar
      desglucoanagalloside B concentrations. This was accompanied by cytochrome c
      release and caspase 3/7 activation. A relatively low cytostatic and pro-apoptotic
      response of cancer cells to a desglucoanagalloside B analog, anagallosaponin IV,
      illustrated the specificity of the effects of desglucoanagalloside B, whereas the
      low sensitivity of normal prostate PNT2 cells to desglucoanagalloside B showed
      the selectivity of its action. Inhibition of cancer cell motility was observed in
      the presence of both saponins, however only desglucoanagalloside B attenuated
      cancer cell invasive potential, predominantly through an effect on cell elastic
      properties. These data demonstrate the versatility of its effects on prostate
      cancer cells. In contrast to PNT2 cells, cancer cells tested in this study were
      relatively resistant to mitoxantrone. The multifaceted action of
      desglucoanagalloside B on basic cellular traits, crucial for prostate cancer
      progression, opens perspectives for elaboration of combined palliative therapies
      and new prostate cancer prophylaxis regimens.

PMID- 23954720
TI  - Protective effects of diphenyl diselenide in a mouse model of brain toxicity.
AB  - Interest in organoselenide chemistry and biochemistry has increased in the past
      three decades, mainly due to their chemical and biological activities. Here, we
      investigated the protective effect of the organic selenium compound diphenyl
      diselenide (PhSe)2 (5 MUmol/kg), in a mouse model of methylmercury (MeHg)-induced
      brain toxicity. Our group has previously demonstrated that the oral and repeated
      administration (21 days) of MeHg (40 mg/L) induced MeHg brain accumulation at
      toxic concentrations, and a pattern of severe cortical and cerebellar biochemical
      and behavioral. In order to assess neurotoxicity, the neurochemical parameters,
      namely, mitochondrial complexes I, II, II-III and IV, glutathione peroxidase
      (GPx) and glutathione reductase (GR) activities, the content of thiobarbituric
      acid-reactive substances (TBA-RS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and
      brain-derived neurotrophic factor (BDNF), as well as, metal deposition were
      investigated in mouse cerebral cortex. Cortical neurotoxicity induced by brain
      MeHg deposition was characterized by the reduction of complexes I, II, and IV
      activities, reduction of GPx and increased GR activities, increased TBA-RS and 8
      OHdG content, and reduced BDNF levels. The daily treatment with (PhSe)2 was able
      to counteract the inhibitory effect of MeHg on mitochondrial activities, the
      increased oxidative stress parameters, TBA-RS and 8-OHdG levels, and the
      reduction of BDNF content. The observed protective (PhSe)2 effect could be linked
      to its antioxidant properties and/or its ability to reduce MeHg deposition in
      brain, which was here histochemically corroborated. Altogether, these data
      indicate that (PhSe)2 could be consider as a neuroprotectant compound to be
      tested under neurotoxicity.

PMID- 23954721
TI  - Antimicrobial responses of teleost phagocytes and innate immune evasion
      strategies of intracellular bacteria.
AB  - During infection, macrophage lineage cells eliminate infiltrating pathogens
      through a battery of antimicrobial responses, where the efficacy of these innate
      immune responses is pivotal to immunological outcomes. Not surprisingly, many
      intracellular pathogens have evolved mechanisms to overcome macrophage defenses,
      using these immune cells as residences and dissemination strategies. With
      pathogenic infections causing increasing detriments to both aquacultural and wild
      fish populations, it is imperative to garner greater understanding of fish
      phagocyte antimicrobial responses and the mechanisms by which aquatic pathogens
      are able to overcome these teleost macrophage barriers. Insights into the
      regulation of macrophage immunity of bony fish species will lend to the
      development of more effective aquacultural prophylaxis as well as broadening our
      understanding of the evolution of these immune processes. Accordingly, this
      review focuses on recent advances in the understanding of teleost macrophage
      antimicrobial responses and the strategies by which intracellular fish pathogens
      are able to avoid being killed by phagocytes, with a focus on Mycobacterium
      marinum. 

PMID- 23954722
TI  - Expression of heat shock protein 90 genes during early development and infection
      in Megalobrama amblycephala and evidence for adaptive evolution in teleost.
AB  - Heat shock protein 90 (HSP90) are highly conserved molecular chaperones, playing
      a pivotal role in cellular progress. In this study, we reported the
      characterization of the Hsp90alpha and Hsp90beta genes in Megalobrama
      amblycephala, the expression profiling during early development, in various
      healthy tissues and in response to bacterial infection, and the assessment of
      their adaptive evolution. The Hsp90alpha cDNA contains an open reading frame
      (ORF) of 2193 bp encoding 731 amino acids and the Hsp90beta cDNA has an ORF of
      2184 bp encoding 728 amino acids. Using quantitative real-time PCR (qRT-PCR)
      analysis, the mRNA of both Hsp90alpha and Hsp90beta reached the highest level at
      15th day post-hatch. Using qRT-PCR and Western blot, both Hsp90alpha and
      Hsp90beta were widely expressed in various healthy tissues and significantly
      higher in blood than in other tissues. Expression of both Hsp90alpha and
      Hsp90beta were up-regulated upon bacterial infection and reached the peak level
      at 4 h post infection. Site model analysis indicated that one positive selection
      site (T717) in Hsp90alpha was found, while no positive selection site was
      observed in Hsp90beta. Branch-site model test showed that there were adaptively
      evolutionary evidences in the branches of Salmoniformes and Gasterosteiformes for
      Hsp90alpha gene, and in the branch of Salmoniformes for Hsp90beta gene.

PMID- 23954723
TI  - Cadmium triggers kidney cell apoptosis of purse red common carp (Cyprinus carpio)
      without caspase-8 activation.
AB  - Caspase-8, the essential initiator caspase, is believed to play a pivotal role in
      death receptor-mediated apoptotic pathway. It also participates in mitochondria
      mediated apoptosis via cleavage of proapoptotic Bid in mammals. However, its role
      in fish remains elusive in Cadmium-induced apoptotic pathway. In this study, we
      isolated the caspase-8 gene from common carp, one of the most important
      industrial aquatic animals in China using rapid amplification of cDNA ends
      (RACE). The deduced amino acid sequence of caspase-8 comprised 475 amino acids,
      which showed approximately 64.1% identity and 79.8% similarity to zebrafish
      (Danio rerio) caspase-8, possessed two conserved death effector domains, a large
      subunit and a small subunit. Phylogenetic analysis demonstrated that caspase-8
      formed a clade with zebrafish caspase-8. In kidney, cadmium (Cd) exposure
      triggered apoptosis and increased caspase-3 and -9 activities, whereas it did not
      affect caspase-8 activity. Real-time quantitative PCR analysis revealed that
      caspase-8 transcriptional level was not significantly increased in kidney after
      exposure to Cd. Using Western blot analysis, no caspase-8 cleaved fragment was
      detected and no significant alteration of procaspase-8 level was found with the
      same Cd-treated condition. Moreover, the immunopositive staining was
      predominantly limited to the cytoplasm of renal tubular epithelial cells and no
      remarkable changes of immunoreactivities were observed using immunohistochemical
      detection after Cd treatment. The results reveal that Cd can trigger apoptosis,
      while it cannot activate caspase-8 in purse red common carp. 

PMID- 23954724
TI  - Mediators in psychological treatment of social anxiety disorder: individual
      cognitive therapy compared to cognitive behavioral group therapy.
AB  - According to cognitive-behavioral models of social anxiety disorder (SAD), four
      of the important maintaining mechanisms are avoidance, self-focused attention,
      anticipatory processing and post-event cognitive processing. Individual cognitive
      therapy (ICT) and cognitive behavioral group therapy (CBGT) both have substantial
      empirical support. However, it is unclear whether they achieve their effects by
      similar or different mechanisms. The aim of this study was to investigate whether
      changes in the four maintenance processes mediate clinical improvement in ICT and
      CBGT for SAD. We analyzed data from participants (N = 94) who received either ICT
      or CBGT in two separate RCTs. The results showed that ICT had larger effects than
      CBGT on social anxiety and each of the four potential mediators. More
      pertinently, moderated mediation analyses revealed significant between-treatment
      differences. Whereas improvement in ICT was mainly mediated by reductions in
      avoidance and self-focused attention, improvement in CBGT was mediated by changes
      in self-focused attention and in anticipatory and post-event processing. These
      results support the importance of the putative mediators, but suggest that their
      relative weights are moderated by treatment type.

PMID- 23954725
TI  - False start: cotranslational protein ubiquitination and cytosolic protein quality
      control.
AB  - Maintaining proteostasis is crucial to cells given the toxic potential of
      misfolded proteins and aggregates. To this end, cells rely on a number of quality
      control pathways that survey proteins both during, as well as after synthesis to
      prevent protein aggregation, promote protein folding, and to target terminally
      misfolded proteins for degradation. In eukaryotes, the ubiquitin proteasome
      system plays a critical role in protein quality control by selectively targeting
      proteins for degradation. Recent studies have added to our understanding of
      cytosolic protein quality control, particularly in the area of cotranslational
      protein ubiquitination, and suggest that overlap exists across co- and post
      translational protein quality control networks. Here, we review recent advances
      made in the area of cytoplasmic protein quality control with an emphasis on the
      pathways involved in cotranslational degradation of eukaryotic cytosolic
      proteins. BIOLOGICAL SIGNIFICANCE: Protein homeostasis, or proteostasis,
      encompasses the systems required by the cell for the generation and maintenance
      of the correct levels, conformational state, distribution, and degradation of its
      proteome. One of the challenges faced by the cell in maintaining proteostasis is
      the presence of misfolded proteins. Cells therefore have a number of protein
      quality control pathways to aid in folding or mediate the degradation of
      misfolded proteins. The ubiquitin proteasome system in particular plays a
      critical role in protein quality control by selectively targeting proteins for
      degradation. Nascent polypeptides can be ubiquitinated cotranslationally, however
      to what extent and how this is used by the cell as a quality control mechanism
      has, until recently, remained relatively unclear. The picture now emerging is one
      of two quality control networks: one that recognizes nascent polypeptides on
      stalled ribosomes and another that targets actively translating polypeptides that
      misfold, failing to attain their native conformation. These studies underscore
      the important balance between cotranslational protein folding and degradation in
      the maintenance of protein homeostasis. In this review we summarize recent
      advances made in the area of cytoplasmic protein quality control with an emphasis
      on pathways involved in cotranslational degradation of eukaryotic cytosolic
      proteins. This article is part of a Special Issue entitled: Can Proteomics Fill
      the Gap Between Genomics and Phenotypes?

PMID- 23954726
TI  - Why are Iraq and Afghanistan War veterans seeking PTSD disability compensation at
      unprecedented rates?
AB  - The wars in Iraq and Afghanistan have produced historically low rates of
      fatalities, injuries, and posttraumatic stress disorder (PTSD) among U.S.
      combatants. Yet they have also produced historically unprecedented rates of PTSD
      disability compensation seeking from the U.S. Department of Veterans Affairs. The
      purpose of this article is to consider hypotheses that might potentially resolve
      this paradox, including high rates of PTSD, delayed onset PTSD, malingered PTSD,
      and economic variables. 

PMID- 23954727
TI  - SPoC: a novel framework for relating the amplitude of neuronal oscillations to
      behaviorally relevant parameters.
AB  - Previously, modulations in power of neuronal oscillations have been functionally
      linked to sensory, motor and cognitive operations. Such links are commonly
      established by relating the power modulations to specific target variables such
      as reaction times or task ratings. Consequently, the resulting spatio-spectral
      representation is subjected to neurophysiological interpretation. As an
      alternative, independent component analysis (ICA) or alternative decomposition
      methods can be applied and the power of the components may be related to the
      target variable. In this paper we show that these standard approaches are
      suboptimal as the first does not take into account the superposition of many
      sources due to volume conduction, while the second is unable to exploit available
      information about the target variable. To improve upon these approaches we
      introduce a novel (supervised) source separation framework called Source Power
      Comodulation (SPoC). SPoC makes use of the target variable in the decomposition
      process in order to give preference to components whose power comodulates with
      the target variable. We present two algorithms that implement the SPoC approach.
      Using simulations with a realistic head model, we show that the SPoC algorithms
      are able extract neuronal components exhibiting high correlation of power with
      the target variable. In this task, the SPoC algorithms outperform other commonly
      used techniques that are based on the sensor data or ICA approaches. Furthermore,
      using real electroencephalography (EEG) recordings during an auditory steady
      state paradigm, we demonstrate the utility of the SPoC algorithms by extracting
      neuronal components exhibiting high correlation of power with the intensity of
      the auditory input. Taking into account the results of the simulations and real
      EEG recordings, we conclude that SPoC represents an adequate approach for the
      optimal extraction of neuronal components showing coupling of power with
      continuously changing behaviorally relevant parameters. 

PMID- 23954728
TI  - Parent abuse by adolescents with first-episode psychosis in Egypt.
AB  - PURPOSE: To determine the rate of parent abuse in a sample of Egyptian
      adolescents with first-episode psychosis (FEP) and to identify the association
      between parent abuse and a number of sociodemographic and clinical factors of
      interest in these patients. As yet, the abuse of parents by their children,
      especially mentally ill children, in contrast to child abuse, has remained a
      research taboo. METHODS: In a cross-sectional study in Zagazig (Egypt), a sample
      of 150 adolescent outpatients (82 boys; 68 girls), presenting with FEP, was
      assessed for the occurrence of parent abuse using both interview and
      questionnaire methods (Abused Parent Questionnaire, APQ). Univariate analyses
      were used to compare parent abusers and nonabusers along a number of
      sociodemographic and clinical variables. Variables that were associated with
      parent abuse were entered into a multivariate logistic regression analysis model.
      RESULTS: We found that 61 patients (40.7%) perpetrated abuse against parents,
      mostly mothers (55/61; 90.2%). Five significant risk factors for parent abuse
      were identified by multivariate analysis. These were parent's female gender (95%
      CI = 7.82-45.56), patient's male gender (95% CI = 3.15-37.14), Childhood Trauma
      Questionnaire - Short Form total score (95% CI = 1.48-14.91), Positive and
      Negative Syndrome Scale positive subscale score (95% CI = 1.26-9.59), and
      duration of untreated psychosis (95% CI = 1.01-4.72). CONCLUSIONS: The study
      indicates that parent abuse, particularly mother abuse, in untreated adolescents
      with FEP is an issue calling for increased awareness of the problem. The findings
      may have important implications for parental psychoeducation and support, and
      earlier access to treatment.

PMID- 23954729
TI  - Measuring school health center impact on access to and quality of primary care.
AB  - PURPOSE: School health centers (SHC) that provide comprehensive health care may
      improve access and quality of care for students; however, published impact data
      are limited. METHODS: We evaluated access and quality of health services at an
      urban high school with a SHC compared with a school without a SHC, using a
      quasiexperimental research design. Data were collected at the beginning of the
      school year, using a paper and pencil classroom questionnaire (n = 2,076
      students). We measured SHC impact in several ways including grade by school
      interaction terms. RESULTS: Students at the SHC school were more likely to report
      having a regular healthcare provider, awareness of confidential services, support
      for health services in their school, and willingness to utilize those services.
      Students in the SHC school reported higher quality of care as measured by:
      respect for their health concerns, adequate time with the healthcare provider,
      understandable provider communications, and greater provider discussion at their
      last visit on topics such as sexual activity, birth control, emotions, future
      plans, diet, and exercise. Users of the SHC were also more likely to report
      higher quality of care, compared with either nonusers or students in the
      comparison school. CONCLUSIONS: Access to comprehensive health services via a SHC
      led to improved access to health care and improved quality of care. Impact was
      measureable on a school-wide basis but was greater among SHC users.

PMID- 23954730
TI  - Free and nanoencapsulated curcumin suppress beta-amyloid-induced cognitive
      impairments in rats: involvement of BDNF and Akt/GSK-3beta signaling pathway.
AB  - Alzheimer's disease (AD), a neurodegenerative disorder exhibiting progressive
      loss of memory and cognitive functions, is characterized by the presence of
      neuritic plaques composed of neurofibrillary tangles and beta-amyloid (Abeta)
      peptide. Drug delivery to the brain still remains highly challenging for the
      treatment of AD. Several studies have been shown that curcumin is associated with
      anti-amyloidogenic properties, but therapeutic application of its beneficial
      effects is limited. Here we investigated possible mechanisms involved in curcumin
      protection against Abeta(1-42)-induced cognitive impairment and, due to its poor
      bioavailability, we developed curcumin-loaded lipid-core nanocapsules in an
      attempt to improve the neuroprotective effect of this polyphenol. Animals
      received a single intracerebroventricular injection of Abeta(1-42) and they were
      administered either free curcumin or curcumin-loaded lipid-core nanocapsules (Cur
      LNC) intraperitoneally for 10days. Abeta(1-42)-infused animals showed a
      significant impairment on learning-memory ability, which was paralleled by a
      significant decrease in hippocampal synaptophysin levels. Furthermore, animals
      exhibited activated astrocytes and microglial cells, as well as disturbance in
      BDNF expression and Akt/GSK-3beta signaling pathway, beyond tau
      hyperphosphorylation. Our findings demonstrate that administration of curcumin
      was effective in preventing behavioral impairments, neuroinflammation, tau
      hyperphosphorylation as well as cell signaling disturbances triggered by Abeta in
      vivo. Of high interest, Cur-LNC in a dose 20-fold lower presented similar
      neuroprotective results compared to the effective dose of free curcumin.
      Considered overall, the data suggest that curcumin is a potential therapeutic
      agent for neurocognition and nanoencapsulation of curcumin in LNC might
      constitute a promising therapeutic alternative in the treatment of
      neurodegenerative diseases such as AD. 

PMID- 23954732
TI  - No notes, no defense: improving documentation in neurosurgery.

PMID- 23954731
TI  - Controlled protein release from monodisperse biodegradable double-wall
      microspheres of controllable shell thickness.
AB  - Biodegradable polymer microparticles are promising delivery depots for protein
      therapeutics due to their relatively simple fabrication and facile
      administration. Double-wall microspheres (DWMS) comprising a core and shell made
      of two distinct polymers may provide enhanced control of the drug release
      profiles. Using precision particle fabrication (PPF) technology, monodisperse
      DWMS were fabricated with model protein bovine serum albumin (BSA)-loaded
      poly(lactide-co-glycolide) (PLG) core and drug-free poly(d,l-lactic acid) (PDLL)
      shell of uniform thickness. Monolithic single-wall microspheres were also
      fabricated to mimic the BSA-loaded PLG core. Using ethyl acetate and
      dichloromethane as shell- and core-phase solvents, respectively, BSA was
      encapsulated selectively in the core region within DWMS with higher loading and
      encapsulation efficiency compared to using dichloromethane as core and shell
      solvents. BSA in vitro release rates were retarded by the presence of the drug
      free PDLL shell. Moreover, increasing PDLL shell thickness resulted in decreasing
      BSA release rate. With a 14-MUm thick PDLL shell, an extended period of constant
      rate release was achieved. 

PMID- 23954733
TI  - Traumatic brain injury in a rural and an urban Tanzanian hospital--a comparative,
      retrospective analysis based on computed tomography.
AB  - BACKGROUND: In a resource-poor environment such as rural East Africa, expensive
      medical devices such as computed tomographic (CT) scanners are rare. The CT
      scanner at the rural Haydom Lutheran Hospital (HLH) in Tanzania therefore offers
      a unique chance to observe possible differences with urban medical centers in the
      disease pattern of trauma-related cranial pathologies. The purpose of this study
      was to compare traumatic brain injuries (TBIs) between a rural and an urban area
      of Tanzania. METHODS: HLH has 350 beds and one CT scanner. The urban Aga Khan
      Hospital is a private hospital with 80 beds and one CT scanner. This was a
      retrospective study. Data of 248 patients at HLH and of 432 patients at Aga Khan
      Hospital with TBI could be collected. RESULTS: The prevalence of TBI was
      significantly higher in the rural area compared to the urban area (34.2% vs.
      21.9%, P < 0.0001). TBI due to violence was noted to occur more frequently at
      HLH, whereas road traffic accidents were more frequent at the Aga Khan Hospital.
      The number of patients showing a normal CT result was significantly higher in the
      urban area (53.0% vs. 35.9%, P < 0.0001). Bone fractures (35.9% vs. 15.7%, P <
      0.0001) and pneumocephalus (6.9% vs. 0.9%, P < 0.0001) were diagnosed
      significantly more frequently in the rural survey. Soft tissue swelling (11.6%
      vs. 1.2%, P < 0.0001) and frontal sinus injuries (7.4% vs. 0.4%, P < 0.0001) were
      observed significantly more often in the urban setting. CONCLUSIONS: This study
      documents the burden of TBI and the differences in TBI-related CT diagnoses and
      their incidence between urban and rural areas in Eastern Africa. These results
      are important as they demonstrate that patients with severe TBI are not a
      primarily urban concern. Management of TBI should be included in the training
      curricula for health personnel alike irrespective of whether their workplace is
      primarily urban or rural.

PMID- 23954734
TI  - Effectiveness of gabapentin in unilateral atlantoaxial osteoarthritis as a cause
      of painful neck.

PMID- 23954735
TI  - Treatment modality and vasospasm after aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Vasospasm is the leading source of neurological morbidity after
      aneurysmal subarachnoid hemorrhage. Our objective was to evaluate the impact of
      treatment modality on vasospasm, delayed cerebral infarction, and clinical
      deterioration caused by delayed cerebral ischemia (CD-DCI). METHODS: We reviewed
      an institutional cohort, comparing rates of vasospasm, delayed cerebral
      infarction, and CD-DCI between patients managed with only microsurgical clipping
      and those treated with only endovascular coiling within 72 hours of rupture. Age,
      sex, smoking status, Hunt-Hess grade, and Fisher grade were adjusted for in a
      multivariate regression model. RESULTS: Two hundred three patients were treated
      with clipping and 52 with coiling. There was no significant difference in patient
      age, sex, smoking status, aneurysm location, and presenting clinical (Hunt-Hess)
      and radiographic (Fisher) grade between these two groups. Sixty-percent of
      patients had moderate or severe vasospasm after clipping compared with 38% after
      coiling (Multivariate odds ratio [OR] 2.32, 95% confidence interval [95% CI] 1.21
      4.47, P = 0.01). Clipping was associated with a greater number of territories
      with vasospasm (mean of 3.1 vs. 2.3, P = 0.03 after multivariate analysis).
      Delayed radiographic cerebral infarction was more common in the clipping group
      (17% vs. 6%, multivariate OR 3.66, 95% CI 1.06-12.71, P = 0.04). For CD-DCI, a
      trend was seen as 16% of patients treated with clipping had CD-DCI compared with
      6% of patients treated with coiling (multivariate OR 3.11, 95% CI 0.89-10.86, P =
      0.07). CONCLUSION: We demonstrate significantly lower rates of vasospasm and
      delayed infarction after endovascular coiling of ruptured aneurysms.

PMID- 23954736
TI  - Follow-up on a national survey: american neurosurgery resident opinions on the
      2011 accreditation council for graduate medical education-implemented duty hours.
AB  - OBJECTIVE: We previously performed a nationwide survey of American neurosurgical
      residents before the initiation of the 2011 Accreditation Council for Graduate
      Medical Education regulations, in which more than 70% indicated the proposed
      changes would negatively impact residency training. We sought to resurvey the
      resident population as to the actual changes that occurred to their programs
      after the 2011 standards went into effect. METHODS: Surveys were mailed to every
      neurosurgery training program in the United States and Puerto Rico. Program
      directors and coordinators were asked to distribute surveys to their residents.
      RESULTS: A total of 253 neurosurgery residents responded. Reported duty-hour
      violations were largely unchanged after the 2011 duty-hour changes. Sixty-percent
      of residents reported that they had underreported duty hours, with nearly 25% of
      respondents doing so on a weekly or daily basis. Most reported that the 2011
      changes had not affected operative caseload, academic productivity, quality of
      life, or resident fatigue. The majority of residents disagreed or strongly
      disagreed that the PGY-1 16-hour limitation had a positive impact on first-year
      resident training (69%) or had improved patient safety (62%). Overall, the
      majority of respondents reported that the 2011 changes had a negative (35%) or
      negligible (33%) effect on residency training at their institution. CONCLUSION:
      Respondents indicated that the 2011 Accreditation Council for Graduate Medical
      Education regulations have had a smaller perceived effect on neurosurgical
      training programs than previously predicted. However, the majority of residents
      admitted to underreporting duty hours, with a quarter doing so on a regular
      basis. The 16-hour rule for interns remains unpopular.

PMID- 23954737
TI  - Perceptual and cognitive effects of antipsychotics in first-episode
      schizophrenia: the potential impact of GABA concentration in the visual cortex.
AB  - Schizophrenia is characterized by anomalous perceptual experiences (e.g., sensory
      irritation, inundation, and flooding) and specific alterations in visual
      perception. We aimed to investigate the effects of short-term antipsychotic
      medication on these perceptual alterations. We assessed 28 drug-naive first
      episode patients with schizophrenia and 20 matched healthy controls at baseline
      and follow-up 8 weeks later. Contrast sensitivity was measured with steady- and
      pulsed-pedestal tests. Participants also received a motion coherence task, the
      Structured Interview for Assessing Perceptual Anomalies (SIAPA), and the
      Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
      Proton magnetic resonance spectroscopy was used to measure gamma-aminobutyric
      acid (GABA) levels in the occipital cortex (GABA/total creatine [Cr] ratio).
      Results revealed that, comparing baseline and follow-up values, patients with
      schizophrenia exhibited a marked sensitivity reduction on the steady-pedestal
      test at low spatial frequency. Anomalous perceptual experiences were also
      significantly ameliorated. Antipsychotic medications had no effect on motion
      perception. RBANS scores showed mild improvements. At baseline, but not at follow
      up, patients with schizophrenia outperformed controls on the steady-pedestal test
      at low spatial frequency. The dysfunction of motion perception (higher coherence
      threshold in patients relative to controls) was similar at both assessments.
      There were reduced GABA levels in schizophrenia at both assessments, which were
      not related to perceptual functions. These results suggest that antipsychotics
      dominantly affect visual contrast sensitivity and anomalous perceptual
      experiences. The prominent dampening effect on low spatial frequency in the
      steady-pedestal test might indicate the normalization of putatively overactive
      magnocellular retino-geniculo-cortical pathways.

PMID- 23954738
TI  - Cognitive and neuropsychiatric correlates of EEG dynamic complexity in patients
      with Alzheimer's disease.
AB  - This study assessed the utility of multiscale entropy (MSE), a complexity
      analysis of biological signals, to identify changes in dynamics of surface
      electroencephalogram (EEG) in patients with Alzheimer's disease (AD) that was
      correlated to cognitive and behavioral dysfunction. A total of 108 AD patients
      were recruited and their digital EEG recordings were analyzed using MSE methods.
      We investigate the appropriate parameters and time scale factors for MSE
      calculation from EEG signals. We then assessed the within-subject consistency of
      MSE measures in different EEG epochs and correlations of MSE measures to
      cognitive and neuropsychiatric symptoms of AD patients. Increased severity of AD
      was associated with decreased MSE complexity as measured by short-time scales,
      and with increased MSE complexity as measured by long-time scales. MSE complexity
      in EEGs of the temporal and occipitoparietal electrodes correlated significantly
      with cognitive function. MSE complexity of EEGs in various brain areas was also
      correlated to subdomains of neuropsychiatric symptoms. MSE analysis revealed
      abnormal EEG complexity across short- and long-time scales that were correlated
      to cognitive and neuropsychiatric assessments. The MSE-based EEG complexity
      analysis may provide a simple and cost-effective method to quantify the severity
      of cognitive and neuropsychiatric symptoms in AD patients. 

PMID- 23954739
TI  - Clozapine pre-treatment has a protracted hypolocomotor effect on the induction
      and expression of amphetamine sensitization.
AB  - Amphetamine locomotor sensitization is an animal model for the study of addiction
      and schizophrenia. The antipsychotic clozapine blocks the hyperlocomotion induced
      by an acute injection of amphetamine, but its effect on locomotor sensitization
      after repeated amphetamine administration remains unknown. In the present study
      we investigate the effect of repeated administration of clozapine on the
      induction and expression of amphetamine locomotor sensitization. We propose that
      repeated administration of clozapine blocks the induction and expression of
      amphetamine sensitization. Male Sprague-Dawley rats were classified according to
      their locomotor response to an acute saline injection in high responder saline
      (HRS) or low responder saline (LRS). Rats from both groups were injected once
      daily with amphetamine for 5 consecutive days. Horizontal locomotor activity was
      measured during 40 min. Four days after the last injection, an acute dose of
      amphetamine was administered to assess the expression of sensitization. Clozapine
      was injected once daily for 4 consecutive days before (pre-treatment) or after
      (treatment) induction of sensitization. Pre-treatment with clozapine
      significantly decreases both acute amphetamine-induced hyperlocomotion and the
      induction and expression of amphetamine sensitization only in LRS rats, showing a
      protracted hypolocomotor effect. On the other hand, clozapine treatment had no
      effect over locomotor response on the expression of amphetamine sensitization in
      either LRS or HRS rats. These data suggest that clozapine effect on amphetamine
      locomotor response depends on individual differences. Also, our results suggest
      that clozapine pre-treatment attenuates the neuroplasticity underlying
      amphetamine sensitization, but clozapine treatment is unable to reverse these
      changes once amphetamine sensitization has been induced.

PMID- 23954740
TI  - Increased frequency of T cells expressing IL-10 in Alzheimer disease but not in
      late-onset depression patients.
AB  - Higher risk of dementia is expected for patients with late onset depression (LOD)
      history. The IL-10 polymorphisms are associated with Alzheimer disease (AD). On
      the other hand, there is no study associating IL-10 polymorphisms to LOD. This
      study aimed to investigate the -1082G/A polymorphism association in LOD, AD
      patients and controls and also the peripheral expression of IL-10 in CD4+ T
      cells. It was done in a case-control study comparing immune system phenotype and
      genetic polymorphism association among control individuals, LOD and AD patients.
      Participants were 569 subjects composed the genetics sample (249 AD, 222 LOD and
      98 controls) from a tertiary medical center based on Belo Horizonte, Brazil. Flow
      cytometry analysis was performed in 55 people (22 AD patients, 11 LOD patients
      and 22 controls). A real time PCR for IL-10 SNP (rs 1800896) through genotyping
      analysis and flow cytometry evaluation of CD4+ T cells expressing IL-10 was done.
      An increased CD4+ T cells expressing IL-10 were detected only in the AD group.
      There was no difference detected in allele or genotype analysis for IL-10
      polymorphism among LOD, AD patients or controls. IL-10 might have a role in the
      modulation of immune response in AD patients, however it is not presented in LOD
      population. 

PMID- 23954741
TI  - Estrogen receptor beta in breast cancer.
AB  - Estrogen is essential for growth and development of the mammary glands and has
      been associated with the promotion and growth of breast cancer and in line with
      this, most human breast cancers are initially estrogen-dependent and undergo
      regression when deprived of their supporting hormone. Estrogen exerts many of its
      effects via two nuclear estrogen receptors (ERs), ERalpha and ERbeta. The
      discovery of a second ER, ERbeta, demanded a full re-evaluation of estrogen
      action in all target tissues and different estrogen associated diseases,
      including human breast cancer. However, despite over 15 years of research, the
      exact role, if any, of ERbeta in human breast cancer remains elusive. The main
      challenges now are to develop highly selective anti-ERbeta antibodies that are
      applied to large well characterized human breast cancer samples to validate their
      diagnostic potential and to explore ERbeta-selective agonists in animal models of
      breast cancer to validate their therapeutic potential.

PMID- 23954743
TI  - Inhibition of ROCK2 expression protects against methamphetamine-induced
      neurotoxicity in PC12 cells.
AB  - Methamphetamine is a type of psychoactive drug. It is well known that
      neurotoxicity caused by Methamphetamine(METH) can damage the nervous system and
      lead to apoptosis and cell loss of dopaminergic neurons. ROCK2 is a prominent
      target for gene therapy because its inhibition has proved to have a protective
      effect in various cell lines and pathophysiological conditions. Although several
      of the negative effects of METH on the dopaminergic system have been studied, the
      protective molecular mechanisms and the effective treatment of METH-induced
      apoptosis remain to be clarified. We hypothesized that ROCK2 is involved in METH
      induced apoptosis. We tested our hypothesis using RT-PCR and western blotting to
      analyze whether silencing of ROCK2 with small interfering RNA (siROCK2) could
      reduce damage and apoptosis in PC12 cells after METH exposure. Increases in
      viability and cytomorphological changes were detected by MTT assay and bright
      field microscopy after pretreatment of METH-treated PC12 cells with 100 nM
      siROCK2. Apoptosis decreased significantly after ROCK2 silencing, as shown by
      Annexin V and TUNEL staining. The results show that ROCK2 is a possible gene
      target for therapeutics in METH-induced neurotoxicity in vitro, providing a
      foundation for future in vivo research.

PMID- 23954742
TI  - MicroRNA-106b induces mitochondrial dysfunction and insulin resistance in C2C12
      myotubes by targeting mitofusin-2.
AB  - MicroRNA-106b (miR-106b) is reported to correlate closely with skeletal muscle
      insulin resistance and type 2 diabetes. The aim of this study was to identify an
      mRNA targeted by miR-106b which regulates skeletal muscle insulin sensitivity.
      MiR-106b was found to target the 3' untranslated region (3' UTR) of mitofusin-2
      (Mfn2) through miR-106b binding sites and to downregulate Mfn2 protein abundance
      at the post-transcriptional level by luciferase activity assay combined with
      mutational analysis and immunoblotting. Overexpression of miR-106b resulted in
      mitochondrial dysfunction and insulin resistance in C2C12 myotubes. MiR-106b was
      increased in insulin-resistant cultured C2C12 myotubes induced by TNF-alpha, and
      accompanied by increasing Mfn2 level, miR-106b loss of function improved
      mitochondrial function and insulin sensitivity impaired by TNF-alpha in C2C12
      myotubes. In addition, both overexpression and downregulation of miR-106b
      upregulated peroxisome proliferator-activated receptor gamma coactivator (PGC)
      1alpha and estrogen-related receptor (ERR)-alpha expression. MiR-106b targeted
      Mfn2 and regulated skeletal muscle mitochondrial function and insulin
      sensitivity. Therefor, Inhibition of miR-106b may be a potential new strategy for
      treating insulin resistance and type 2 diabetes. 

PMID- 23954744
TI  - Dissociation of decision making under ambiguity and decision making under risk in
      breast cancer patients receiving adjuvant chemotherapy: a neuropsychological
      study.
AB  - There is evidence that women with breast cancer show a cognitive impairment after
      having undergone chemotherapy treatment; this cognitive impairment may result in
      behavioral deficits. However, the neural mechanism of this cognitive impairment
      remains unclear. The present study investigated the neural basis of the cognitive
      impairment caused by chemotherapy treatment by exploring the decision-making
      function of the executive subcomponents under ambiguity and risk in breast cancer
      survivors. Participants included breast cancer patients who had undergone
      chemotherapy (CT, N=63) or patients who did not undergo chemotherapy (non-CT,
      N=62), as well as matched healthy controls (HC, N=61). All participants were
      examined using the Iowa Gambling Task (IGT) to assess their decision-making under
      ambiguity, the Game of Dice Task (GDT) to assess their decision-making under risk
      and neuropsychological background tests. Our results indicated that during the
      IGT test, the chemotherapy-treated breast cancer patients selected from the
      disadvantageous decks with a higher frequency than the non-treated breast cancer
      patients or healthy controls, whereas all three groups performed at the same
      level when performing the GDT. The CT group demonstrated significantly lower
      scores in several cognitive tasks, including attention, memory, executive
      functions and cognitive processing, when compared with the other two groups. In
      addition, within the CT group, significant correlations were found between the
      IGT performance and information processing, as well as with working memory. This
      study demonstrated that breast cancer survivors treated with chemotherapy may
      have selective reductions in IGT performance but unimpaired GDT performance and
      that these deficits may result from dysfunctions in the limbic loop rather than
      in the dorsolateral prefrontal loop. 

PMID- 23954745
TI  - Chronic cerebral ischemia induces redistribution and abnormal phosphorylation of
      transactivation-responsive DNA-binding protein-43 in mice.
AB  - Transactivation-responsive DNA-binding protein 43 (TDP-43) is closely involved in
      the pathogenesis of frontotemporal lobar degeneration. The native form, but not
      phosphorylated form, of TDP-43 has been reported to redistribute during acute
      neuronal injuries. Here, we examined whether the expression of phosphorylated TDP
      43 was altered following chronic neuronal injury. C57BL/6 mice were subjected to
      sham operation or bilateral common carotid artery stenosis (BCAS) using
      microcoils, and changes in proteolytic cleavage, phosphorylation, and subcellular
      redistribution of TDP-43 were examined by immunoblotting and
      immunohistochemistry. We also monitored the expression of importin beta, which is
      involved in the transport of TDP-43. Immunoblotting showed an increase in
      phosphorylated TDP-43 in the nuclear fraction after BCAS using microcoils.
      Moreover, immunoreactivity toward phosphorylated TDP-43 was observed in the
      neuronal cytoplasm in the cerebral cortex and hippocampus, and importin beta
      levels decreased after the operation. Immunoreactivity toward phosphorylated TDP
      43 was partly colocalized with immunoreactivity toward caspase 3 in the neuronal
      cytoplasm. These results suggested that chronic cerebral ischemia induced
      redistribution and abnormal phosphorylation of TDP-43, which may be triggered by
      downregulation of importin beta and may partly result in neuronal death. 

PMID- 23954746
TI  - Somatosensory conditioning of sexual arousal and copulatory behavior in the male
      rat: a model of fetish development.
AB  - Previous studies have established that neutral olfactory cues associated with
      sexual reward or inhibition become conditioned stimuli that direct male or female
      rats toward or away from potential sex partners bearing the cue. Here we examined
      the ability of a somatosensory cue to exert stimulus control over sexual arousal
      and copulation in male rats. In the first experiment, two groups of sexually
      naive male rats had their first copulatory experiences with receptive females in
      bilevel chambers with or without a rodent jacket. On a final copulatory test,
      half of the rats in each group were tested with the jacket on or off. Rats
      trained and tested without the jacket copulated normally, as did rats trained and
      tested with the jacket on, and rats trained without the jacket but tested with
      the jacket on. However, significantly fewer rats trained with the jacket on but
      tested with the jacket off copulated to ejaculation, and those that did made
      significantly fewer anticipatory level changes and had fewer significantly longer
      mount, intromission, and ejaculatory latencies, and fewer ejaculations. In the
      second experiment, one group of sexually naive males was given differential
      conditioning trials in bilevel chambers to associate the jacket on with sexual
      reward (copulation to ejaculation with a sexually receptive female) and the
      jacket off with sexual inhibition (thwarted copulatory attempts with a sexually
      nonreceptive female). A second group had the opposite order of association. A
      final test with receptive females was made for all males with the jacket on.
      Males trained to associate the jacket with excitation displayed normal copulation
      whereas males trained to associate the jacket with inhibition displayed
      significantly fewer anticipatory level changes and ejaculations, and had
      significantly longer ejaculation latencies. Thus, somatosensory cues can signal
      sexual excitation or inhibition in male rats depending on the conditioning
      history. 

PMID- 23954747
TI  - Elemental analysis of natural quartz from Um Higlig, Red Sea Aea, Egypt by
      instrumental neutron activation analysis.
AB  - A scheme for INAA of 25 elements: As, Ba, Ca, Ce, Co, Cr, Cs, Eu, Fe, Hf, K, La,
      Lu, Mg, Mn, Na, Nd, Rb, Sc, Sm, Th, U, Yb, Zn and Zr in quartz collected from the
      eastern desert along the Egyptian Red Sea coast is proposed. The samples were
      prepared together with standard reference material and irradiated in a neutron
      flux of 7*10(11)n/cm(2)s in the TRIGA Mainz research reactor facilities. The
      gamma spectra were collected by a HPGe detector and the analysis was done by a
      computerized multichannel analyzer.The accuracy of the procedure is evaluated by
      the analysis of two geo-standard reference materials (Dolerite WSE and Microgabro
      PMS). The choice of the nuclear reaction, irradiation and decay times and of the
      proper gamma radiation in counting are presented and discussed. The data
      presented here are our contribution to understanding the elemental composition of
      the quartz rock. Because there are no existing databases for the elemental
      analysis of quartz, our results are a start to establishing a database for the
      Egyptian quartz. It is hoped that the data presented here will be useful to those
      dealing with geochemistry, quartz chemistry and related fields.

PMID- 23954748
TI  - Induction of apoptosis by c9, t11-CLA in human endometrial cancer RL 95-2 cells
      via ERalpha-mediated pathway.
AB  - Numerous studies have shown that conjugated linoleic acid (CLA) can inhibit
      cancer cells growth and induce apoptosis in vitro and in vivo. The aim of the
      present study was to investigate the effects of CLA, including cis9, trans11
      conjugated linoleic acid (c9, t11-CLA) and trans10, cis12-conjugated linoleic
      acid (t10, c12-CLA), on apoptosis of human endometrial cancer RL 95-2 cells and
      its related mechanisms. The MTT analysis was used to evaluate the effect of CLA
      isomers on the viability of endometrial cancer RL 95-2 cells. We then estimated
      the apoptosis by Morphological observation and Annexin V-FITC/PI staining and
      flow cytometry. We also used Western blot analysis to assess the expression of
      caspase-3, Bax, Bcl-2 proteins and the activation of Akt/p-Akt and ERalpha/p
      ERalpha. Propylpyrazole-triol (PPT), a selective ERalpha agonist was used to
      confirm the induction of apoptosis by c9, t11 CLA may relate to ERalpha-mediated
      pathway. In CLA-treated RL 95-2 cells, we found that c9, t11-CLA inhibited
      viability and trigged apoptosis, as judged from nuclear morphology and flow
      cytometric analysis. The expression of caspase-3 and the ratio of Bax/Bcl-2 were
      significant increased, but no obvious change was observed about Akt and p-Akt in
      c9, t11-CLA-treated cells. However, the expression of total ERalpha level in RL
      95-2 cells-treated with c9, t11-CLA was unchanged, while in the concentration of
      80 mM, c9, t11-CLA down-regulated the protein expression level of p-ERalpha. Then
      PPT has the antagonistic action on growth inhibitory effect in RL 95-2 cells
      incubated with c9, t11-CLA. This study demonstrated that c9, t11- CLA could
      induce apoptosis in RL 95-2 cells, and may involve in ERalpha-mediated pathway.
      These results indicated that c9, t11- CLA could induce apoptosis of endometrial
      cancer cells and may be potential agents for the treatment of endometrial cancer.

PMID- 23954749
TI  - Cannabinoids and glucocorticoids modulate emotional memory after stress.
AB  - Bidirectional and functional relationships between glucocorticoids and the
      endocannabinoid system have been demonstrated. Here, I review the interaction
      between the endocannabinoid and glucocorticoid/stress systems. Specifically,
      stress is known to produce rapid changes in endocannabinoid signaling in stress
      responsive brain regions. In turn, the endocannabinoid system plays an important
      role in the downregulation and habituation of hypothalamic-pituitary
      adrenocortical (HPA) axis activity in response to stress. Glucocorticoids also
      recruit the endocannabinoid system to exert rapid negative feedback control of
      the HPA axis during stress. It became increasingly clear, however, that
      cannabinoid CB1 receptors are also abundantly expressed in the basolateral
      amygdala (BLA) and other limbic regions where they modulate emotional arousal
      effects on memory. Enhancing cannabinoids signaling using exogenous CB1 receptor
      agonists prevent the effects of acute stress on emotional memory. I propose a
      model suggesting that the ameliorating effects of exogenously administered
      cannabinoids on emotional learning after acute stress are mediated by the
      decrease in the activity of the HPA axis via GABAergic mechanisms in the
      amygdala. 

PMID- 23954750
TI  - Compensatory plasticity and cross-modal reorganization following early visual
      deprivation.
AB  - For human and non-human primates, vision is one of the most privileged sensory
      channels used to interact with the environment. The importance of vision is
      strongly embedded in the organization of the primate brain as about one third of
      its cortical surface is involved in visual functions. It is therefore not
      surprising that the absence of vision from birth, or the loss of vision later in
      life, has huge consequences, both anatomically and functionally. Studies in
      animals and humans, conducted over the past few decades, have demonstrated that
      the absence of vision causes massive structural changes that take place not only
      in the visually deprived cortex but also in other brain areas. These studies have
      further shown that the visually deprived cortex becomes responsive to a wide
      variety of non-visual sensory inputs. Recent studies even showed a role of the
      visually deprived cortex in cognitive processes. At the behavioral level,
      increases in acuity for auditory and tactile processes have been reported. The
      study of the congenitally blind brain also offers a unique model to gain better
      insights into the functioning of the normal sighted brain and to understand to
      what extent visual experience is necessary for the brain to develop its
      functional architecture. Finally, the study of the blind brain allows us to
      investigate how consciousness develops in the absence of vision. How does the
      brain of someone who has never had any visual perception form an image of the
      external world? In this paper, we discuss recent findings from animal studies as
      well as from behavioural and functional brain imaging studies in sighted and
      blind individuals that address these questions. 

PMID- 23954751
TI  - The epidermis comprises autonomous compartments maintained by distinct stem cell
      populations.
AB  - The complex anatomy of the epidermis contains multiple adult stem cell
      populations, but the extent to which they functionally overlap during
      homeostasis, wound healing, and tumor initiation remains poorly defined. Here, we
      demonstrate that Lrig1(+ve) cells are highly proliferative epidermal stem cells.
      Long-term clonal analysis reveals that Lrig1(+ve) cells maintain the upper
      pilosebaceous unit, containing the infundibulum and sebaceous gland as
      independent compartments, but contribute to neither the hair follicle nor the
      interfollicular epidermis, which are maintained by distinct stem cell
      populations. In contrast, upon wounding, stem cell progeny from multiple
      compartments acquire lineage plasticity and make permanent contributions to
      regenerating tissue. We further show that oncogene activation in Lrig1(+ve) cells
      drives hyperplasia but requires auxiliary stimuli for tumor formation. In
      summary, our data demonstrate that epidermal stem cells are lineage restricted
      during homeostasis and suggest that compartmentalization may constitute a
      conserved mechanism underlying epithelial tissue maintenance. 

PMID- 23954752
TI  - High mitochondrial priming sensitizes hESCs to DNA-damage-induced apoptosis.
AB  - Human embryonic stem cells (hESCs) are highly sensitive to DNA damage and have
      low survival ability relative to differentiated cells. We investigated the source
      of this difference by comparing damage response pathways in hESCs and
      differentiated cells. We found that hESCs undergo more rapid p53-dependent
      apoptosis after DNA damage than differentiated cells do. However, p53
      localization and function are similar between hESCs and differentiated cells,
      suggesting that p53 alone cannot explain the difference in sensitivity. Instead,
      we show that mitochondrial readiness for apoptosis, known as mitochondrial
      priming, differs between hESCs and differentiated cells. Specifically, the
      balance between proapoptotic and antiapoptotic proteins is shifted closer to the
      apoptotic threshold in hESCs than in differentiated cells. Altering this balance
      in differentiated cells increases their sensitivity and results in cell death,
      suggesting that manipulation of mitochondrial priming could potentially alter the
      sensitivity of other stem cells, including cancer stem cells. 

PMID- 23954753
TI  - Facial selectivities in the nucleophilic additions of 2,3-unsaturated 3
      arylsulfinyl pyranosides.
AB  - 2,3-Unsaturated 3-arylsulfinyl pyranosides undergo nucleophilic additions at C-2,
      with facial selectivities depending on the nucleophile and the substituent on
      sulfinyl sulfur. The reactions of such sugar vinyl sulfoxides lead to the
      addition of nucleophile preferring an axial orientation at C-2, with concomitant
      formation of an allylic bond at C-3 to C-4. This trend in the addition pattern is
      observed for primary amine, carbon and sulfur nucleophiles, whereas secondary
      amines prefer an equatorial addition at C-2. The effect of p-tolylthio- versus (p
      isopropylphenyl)thio vinyl sulfoxide is that the equatorial nucleophilic addition
      is preferred even more with the latter vinyl sulfoxide. 

PMID- 23954754
TI  - Measurement, variation, and scaling of osteocyte lacunae: a case study in birds.
AB  - Basic issues surrounding osteocyte biology are still poorly understood, including
      the variability of osteocyte morphology within and among bones, individuals, and
      species. Several studies have suggested that the volume or shape of osteocytes
      (or their lacunae) is related to bone and/or organismal growth rate or
      metabolism, but the nature of this relationship, if any, is unclear. Furthermore,
      several studies have linked osteocyte lacuna volume with genome size or growth
      rate and suggested that osteocyte lacuna volume is unrelated to body size. Herein
      the scaling of osteocyte lacuna volume with body mass, growth and basal metabolic
      rates, genome size, and red blood cell size is examined using a broad sample of
      extant birds within a phylogenetic framework. Over 12,000 osteocyte lacuna axes
      were measured in a variety of bones from 34 avian and four non-avian dinosaur
      species. Osteocyte lacunae in parallel-fibered bone are scalene ellipsoids; their
      morphology and volume cannot be reliably estimated from any single thin section,
      and using a prolate ellipsoid model to estimate osteocyte lacuna volume results
      in a substantial (ca. 2-7 times) underestimate relative to true lacunar volume.
      Orthogonal thin sections reveal that in birds, even when only observing parallel
      fibered, primary, cortical bone, intra-skeletal variation in osteocyte lacuna
      volume and shape is very high (volumes vary by a factor of 5.4 among different
      bones), whereas variation among homologous bones of the same species is low (1.2
      44%; mean=12%). Ordinary and phylogenetically informed bivariate and multiple
      regressions demonstrate that in birds, osteocyte volume scales significantly but
      weakly with body mass and mass-specific basal metabolic rate and moderately with
      genome size, but not with erythrocyte size. Avian whole-body growth rate and
      osteocyte lacuna volume are weakly and inversely related. Finally, we present the
      first three-dimensionally calculated osteocyte volumes for several non-avian
      dinosaurs, which are much larger than previously reported values and smaller than
      those of large extant avians. Osteocyte volumes estimated from a single
      transverse section and assuming prolate morphology, as done in previous studies,
      are relative underestimates in theropod dinosaurs compared to sauropod dinosaurs,
      raising the possibility that no major change in osteocyte volumes (and genome
      size) occurred within Theropoda on the lineage leading to birds. Osteocyte volume
      is intertwined with several organismal attributes whose relative importance
      varies at a number of hierarchical levels. 

PMID- 23954755
TI  - Induced periosteum a complex cellular scaffold for the treatment of large bone
      defects.
AB  - OBJECTIVE: Surgically induced periosteal membrane holds great potential for the
      treatment of large bone defects representing a simple alternative to combinations
      of exogenous stem cells, scaffolds and growth factors. The purpose of this study
      was to explore the biological basis for this novel regenerative medicine strategy
      in man. METHODS: Eight patients with critical size defects were treated with the
      induced membrane (IM) technique. After membrane formation 1cm(2) biopsy was taken
      together with matched, healthy diaphyseal periosteum (P) for comparative
      analysis. Morphological characteristics, cell composition and growth factor
      expression were compared. Functional and molecular evaluation of mesenchymal
      stromal cell (MSC) activity was performed. RESULTS: Both tissues shared similar
      morphology although IM was significantly thicker than P (p=0.032). The frequency
      of lymphocytes, pericytes (CD45(-)CD34(-)CD146(+)) and cells expressing markers
      consistent with bone marrow MSCs (CD45(-/low)CD271(bright)) were 31. 3 and 15.5
      fold higher respectively in IM (all p=0.043). IM contained 3-fold more cells per
      gramme of tissue with a similar proportion of endothelial cells (CD45(-)CD31(+)).
      Expressed bone morphogenic protein 2, vascular endothelial growth factor and
      stromal derived factor 1 (SDF-1) are key tissue regeneration mediators. Adherent
      expanded cells from both tissues had molecular profiles similar to bone marrow
      MSCs but cells from IM expressed greater than 2 fold relative abundance of SDF
      1transcript compared to P (p=0.043). CONCLUSION: The IM is a thick, vascularised
      structure that resembles periosteum with a cellular composition and molecular
      profile facilitating large defect repair and therefore may be described as an
      "induced-periosteum". This tissue offers a powerful example of in situ tissue
      engineering.

PMID- 23954756
TI  - In the shadow of phylogenetic uncertainty: the recent diversification of Lysandra
      butterflies through chromosomal change.
AB  - The phylogeny of the butterfly genus Lysandra (Lycaenidae, Polyommatinae) has
      been intractable using both molecular and morphological characters, which could
      be a result of speciation due to karyotype instability. Here we reconstruct the
      phylogeny of the group using multi-locus coalescent-based methods on seven
      independent genetic markers. While the genus is ca. 4.9 Mya old, the
      diversification of the extant lineages was extremely recent (ca. 1.5 Mya) and
      involved multiple chromosomal rearrangements. We find that relationships are
      uncertain due to both incomplete lineage sorting and hybridization. Minimizing
      the impact of reticulation in inferring the species tree by testing for
      mitochondrial introgression events yields a partially resolved tree with three
      main supported clades: L. punctifera+L. bellargus, the corydonius taxa, and L.
      coridon+the Iberian taxa, plus three independent lineages without apparently
      close relatives (L. ossmar, L. syriaca and L. dezina). Based on these results and
      new karyotypic data, we propose a rearrangement recognizing ten species within
      the genus. Finally, we hypothesize that chromosomal instability may have played a
      crucial role in the Lysandra recent diversification. New chromosome
      rearrangements might be fixed in populations after severe bottlenecks, which at
      the same time might promote rapid sorting of neutral molecular markers. We argue
      that population bottlenecks might be a prerequisite for chromosomal speciation in
      this group. 

PMID- 23954757
TI  - Immature mice are more susceptible to the detrimental effects of high fat diet on
      cancellous bone in the distal femur.
AB  - With the increasing prevalence of obesity among children and adolescents, it is
      imperative to understand the implications of early diet-induced obesity on bone
      health. We hypothesized that cancellous bone of skeletally immature mice is more
      susceptible to the detrimental effects of a high fat diet (HFD) than mature mice,
      and that removing excess dietary fat will reverse these adverse effects.
      Skeletally immature (5weeks old) and mature (20weeks old) male C57BL/6J mice were
      fed either a HFD (60% kcal fat) or low fat diet (LFD; 10% kcal fat) for 12weeks,
      at which point, the trabecular bone structure in the distal femoral metaphysis
      and third lumbar vertebrae were evaluated by micro-computed tomography. The
      compressive strength of the vertebrae was also measured. In general, the HFD led
      to deteriorations in cancellous bone structure and compressive biomechanical
      properties in both age groups. The HFD-fed immature mice had a greater decrease
      in trabecular bone volume fraction (BVF) in the femoral metaphysis, compared to
      mature mice (p=0.017 by 2-way ANOVA). In the vertebrae, however, the HFD led to
      similar reductions in BVF and compressive strength in the two age groups. When
      mice on the HFD were switched to a LFD (HFD:LFD) for an additional 12weeks, the
      femoral metaphyseal BVF in immature mice showed no improvements, whereas the
      mature mice recovered their femoral metaphyseal BVF to that of age-matched lean
      controls. The vertebral BVF and compressive strength of HFD:LFD mouse bones,
      following diet correction, were equivalent to those of LFD:LFD mice in both age
      groups. These data suggest that femoral cancellous metaphyseal bone is more
      susceptible to the detrimental effects of HFD before skeletal maturity and is
      less able to recover after correcting the diet. Negative effects of HFD on
      vertebrae are less severe and can renormalize with LFD:LFD mice after diet
      correction, in both skeletally immature and mature animals. 

PMID- 23954759
TI  - Prospective biomarker evaluation in patients with osteonecrosis of the jaw who
      received bisphosphonates.
AB  - Bone biomarkers have been suggested for the risk assessment for osteonecrosis of
      the jaw, a serious complication associated with bisphosphonate (BP) use; however,
      no consensus has been reached. This study investigated the possible associations
      between bone biomarkers and the development of bisphosphonates-related
      osteonecrosis of the jaw (BRONJ). This is a case-control study of 37 patients
      with BRONJ (age, 73.6+/-11.2years) who had at least 1 sample available at
      diagnosis, out of which, 35 were taking BPs for osteoporosis and 2 patients for
      bone metastasis. Age- and gender-matched 37 patients who had been exposed to BPs
      for >24months and had no evidence of BRONJ after dentoalveolar surgery served as
      control group. The association between biomarkers (osteocalcin [OC],
      deoxypyridinoline [DPD], C-terminal telopeptide of collagen I [CTX], N-terminal
      telopeptides [NTX], bone-specific alkaline phosphatase [BAP], and parathyroid
      hormone [PTH]) and BRONJ development, the effects of BP discontinuation on
      biomarkers, and the performance of biomarkers for risk assessment were
      investigated. In our study, the PTH levels were found to be significantly higher
      in BRONJ patients compared to controls (P<0.05). But the OC, DPD, CTX, NTX, and
      BAP levels were not significantly different between the 2 groups (P>0.05). The
      CTX level in reference to a 150pg/mL cutoff was also not significant for BRONJ
      development (P>0.05). Among BRONJ patients who discontinued BP, in a linear mixed
      model, only CTX showed a significant increase over time (beta=0.002, P=0.007).
      The cutoff PTH level was >41.52pg/mL (AUC=0.719, P=0.009), and that of CTX was
      <=0.094ng/mL (AUC=0.619, P=0.069). In conclusion, there is insufficient evidence
      for the risk prediction for BRONJ of current bone biomarkers; additional research
      is necessary. 

PMID- 23954758
TI  - Quantification of lower leg arterial calcifications by high-resolution peripheral
      quantitative computed tomography.
AB  - Vascular calcifications and bone health seem to be etiologically linked via
      common risk factors such as aging and subclinical chronic inflammation.
      Epidemiologic studies have shown significant associations between low bone
      mineral density (BMD), fragility fractures and calcifications of the coronary
      arteries and the abdominal aorta. In the last decade, high-resolution peripheral
      quantitative computed tomography (HR-pQCT) has emerged as in-vivo research tool
      for the assessment of peripheral bone geometry, density, and microarchitecture.
      Although vascular calcifications are frequently observed as incidental findings
      in HR-pQCT scans, they have not yet been incorporated into quantitative HR-pQCT
      analyses. We developed a semi-automated algorithm to quantify lower leg arterial
      calcifications (LLACs), captured by HR-pQCT. The objective of our study was to
      determine validity and reliability of the LLAC measure. HR-pQCT scans were
      downscaled to a voxel size of 250MUm. After subtraction of bone volumes from the
      scans, LLACs were detected and contoured by a semi-automated, dual-threshold seed
      point segmentation. LLAC mass (in mg hydroxyapatite; HA) was calculated as the
      product of voxel-based calcification volume (mm(3)) and mean calcification
      density (mgHA/cm(3))/1000. To determine validity, we compared LLACs to coronary
      artery calcifications (CACs), as quantified by multi-detector computed tomography
      (MDCT) and Agatston scoring in forty-six patients on chronic hemodialysis.
      Moreover, we investigated associations of LLACs with age, time on dialysis, type
      2 diabetes mellitus, history of stroke, and myocardial infarction. In a second
      step, we determined intra- and inter-reader reliability of the LLAC measure. In
      the validity study, LLACs were present (>0mgHA) in 76% of patients, 78% of
      patients had CACs (>0mgHA). Median LLAC was 6.65 (0.08-24.40)mgHA and median CAC
      as expressed by Agatston score was 266.3 (15.88-1877.28). We found a significant
      positive correlation between LLAC and CAC (rho=0.6; p<0.01). Dialysis patients
      with type-2 diabetes mellitus (DM; 35%) and history of stroke (13%) had higher
      median LLAC than patients without those conditions (DM 20.0 fold greater,
      p=0.006; Stroke 5.1 fold greater, p=0.047). LLAC was positively correlated with
      time on dialysis (rho=0.337, p=0.029), there was a trend towards a positive
      association of LLAC and age (rho=0.289, p=0.053). The reliability study yielded
      excellent intra- and inter-reader agreement of the LLAC measure (intra-reader
      ICC=0.999, 95% CI=0.998-1.000; inter-reader ICC=0.998, 95% CI=0.994-0.999). Our
      study indicates that the LLAC measure has good validity and excellent
      reliability. The use of HR-pQCT for the simultaneous evaluation of arterial
      calcifications, peripheral bone geometry, bone density, and bone
      microarchitecture should facilitate future research on osteo-vascular
      interactions and potential associations with cardiovascular events. 

PMID- 23954760
TI  - Phosphatidylserine metabolism modification precedes manganese-induced apoptosis
      and phosphatidylserine exposure in PC12 cells.
AB  - Long-term exposure to high manganese (Mn) levels can lead to Parkinson-like
      neurological disorders. Molecular mechanisms underlying Mn cytotoxicity have been
      not defined. It is known that Mn induces apoptosis in PC12 cells and that this
      involves the activation of some signal transduction pathways. Although the role
      of phospholipids in apoptosis and signal transduction is well-known, the membrane
      phospholipid component in Mn-related damage has not yet been investigated.
      Phosphatidylserine (PS) facilitates protein translocation from cytosol to plasma
      membrane and PS exposure on the cell surface allows macrophage recognition of
      apoptotic cells. This study investigates the effects of MnCl2 on PS metabolism in
      PC12 cells, relating them to those on cell apoptosis. Apoptosis induction
      decreased PS radioactivity of PC12 cells incubated with radioactive serine. MnCl2
      reduced PS radioactivity even under conditions that did not affect cell viability
      or PS exposure, suggesting that the effects on PS metabolism may represent an
      early event in cell apoptosis. Thus the latter conditions that also induced a
      greater PS decarboxylation were utilized for further investigating on the effects
      on PS synthesis, by measuring the activity and expression of PS-synthesizing
      enzymes, in cell lysates and in total cellular membranes (TM). Compared with
      corresponding controls, enzyme activity of MnCl2-treated cells was lower in cell
      lysates and greater in TM. Evaluating the expression of two isoforms of PS
      synthesizing enzyme (PSS), PSSII was increased both in cell lysate and TM, while
      PSSI was unchanged. MnCl2 addition to control cell lysate reduced enzyme
      activity. These results suggest Mn plays a dual role on PS synthesis. Once inside
      the cell, Mn inhibits the enzyme/s, thus accounting for reduced PS synthesis in
      lysates and intact cells. On the other hand, it increases PSSII expression in
      cell membranes. The possibility that this occurs to counteract the direct effects
      of Mn ions on enzyme activity cannot be excluded. The effects on membrane enzyme
      activity and expression may also participate to PS exposure, observed at longer
      periods of treatment, by increasing membrane PS content. 

PMID- 23954761
TI  - Selective allodepletion: have we finally found the holy grail?

PMID- 23954762
TI  - Letter to the editor.

PMID- 23954764
TI  - Interpersonal communication research in the context of pain.

PMID- 23954763
TI  - Emotional modulation of pain and spinal nociception in persons with major
      depressive disorder (MDD).
AB  - Major depressive disorder (MDD) is associated with risk for chronic pain, but the
      mechanisms contributing to the MDD and pain relationship are unclear. To examine
      whether disrupted emotional modulation of pain might contribute, this study
      assessed emotional processing and emotional modulation of pain in healthy
      controls and unmedicated persons with MDD (14 MDD, 14 controls). Emotionally
      charged pictures (erotica, neutral, mutilation) were presented in 4 blocks. Two
      blocks assessed physiological-emotional reactions (pleasure/arousal ratings,
      corrugator electromyography (EMG), startle modulation, skin conductance) in the
      absence of pain and 2 blocks assessed emotional modulation of pain and the
      nociceptive flexion reflex (NFR, a physiological measure of spinal nociception)
      evoked by suprathreshold electric stimulations. Results indicated pictures
      generally evoked the intended emotional responses; erotic pictures elicited
      pleasure, subjective arousal, and smaller startle magnitudes, whereas mutilation
      pictures elicited displeasure, corrugator EMG activation, and
      subjective/physiological arousal. However, emotional processing was partially
      disrupted in MDD, as evidenced by a blunted pleasure response to erotica and a
      failure to modulate startle according to a valence linear trend. Furthermore,
      emotional modulation of pain was observed in controls but not MDD, even though
      there were no group differences in NFR threshold or emotional modulation of NFR.
      Together, these results suggest supraspinal processes associated with emotion
      processing and emotional modulation of pain may be disrupted in MDD, but brain to
      spinal cord processes that modulate spinal nociception are intact. Thus,
      emotional modulation of pain deficits may be a phenotypic marker for future pain
      risk in MDD. 

PMID- 23954765
TI  - Dietary control of chronic headache: involvement of pro-resolution lipid
      mediators.

PMID- 23954766
TI  - In vitro-in vivo correlations for endocrine activity of a mixture of currently
      used pesticides.
AB  - Two pesticide mixtures were investigated for potential endocrine activity. Mix 3
      consisted of bitertanol, propiconazole, and cypermethrin, and Mix 5 included
      malathion and terbuthylazine in addition to the three pesticides in Mix 3. All
      five single pesticides and the two mixtures were investigated for their ability
      to affect steroidogenesis in vitro in H295R cells. The pesticides alone and both
      mixtures affected steroidogenesis with both mixtures causing increase in
      progesterone and decrease in testosterone. For Mix 5 an increase in estradiol was
      seen as well, indicating increased aromatase activity. The two mixtures were also
      investigated in pregnant rats dosed from gestational day 7 to 21, followed by
      examination of dams and fetuses. Decreased estradiol and reduced placental
      testosterone were seen in dams exposed to Mix 5. Also a significant increase in
      aromatase mRNA-levels in female adrenal glands was found for Mix5. However,
      either of the two mixtures showed any effects on fetal hormone levels in plasma
      or testis, or on anogenital distance. Overall, potential aromatase induction was
      found for Mix 5 both in vitro and in vivo, but not for Mix 3, an effect likely
      owed to terbuthylazine in Mix 5. However, the hormonal responses in vitro were
      only partly reflected in vivo, probably due to some toxicokinetic issues, as the
      pesticide levels in the amniotic fluid also were found to be negatively affected
      by the number of compounds present in the mixtures. Nonetheless, the H295R assay
      gives hints on conceivable interference with steroidogenesis, thus generating
      hypotheses on in vivo effects. 

PMID- 23954767
TI  - Curcumin analog 1, 5-bis (2-trifluoromethylphenyl)-1, 4-pentadien-3-one exhibits
      enhanced ability on Nrf2 activation and protection against acrolein-induced ARPE
      19 cell toxicity.
AB  - Curcumin, a phytochemical agent in the spice turmeric, has received increasing
      attention for its anticancer, anti-inflammatory and antioxidant properties.
      However, application of curcumin has been limited due to its insolubility in
      water and poor bioavailability both clinically and experimentally. In addition,
      the protective effects and mechanisms of curcumin in eye diseases have been
      poorly studied. In the present study, we synthesized a curcumin analog, 1, 5-bis
      (2-trifluoromethylphenyl)-1, 4-pentadien-3-one (C3), which displayed improved
      protective effect against acrolein-induced toxicity in a human retinal pigment
      epithelial cell line (ARPE-19). At 5 MUM, curcumin completely protected against
      acrolein-induced cell oxidative damage and preserved GSH levels and mitochondrial
      function. Surprisingly, C3 displayed a complete protective effect at 0.5 MUM,
      which was much more efficient than curcumin. Both 0.5 MUM C3 and 5 MUM curcumin
      induced Nrf2 nuclear translocation and Nrf2 target genes transcription similarly.
      Experiments using Nrf2 siRNA showed that the protective effects of curcumin and
      C3 were eliminated by Nrf2 knockdown. Additionally, both curcumin and C3
      activated the PI3/Akt pathway, however, Nrf2 activation was independent of this
      pathway, and therefore, we hypothesized that both curcumin and C3 activated phase
      II enzymes via directly disrupting the Nrf2/Keap1 complex and promoting Nrf2's
      nuclear translocation. Since acrolein challenge of ARPE-19 cells has been used as
      a model of smoking and age-related macular degeneration (AMD), we concluded that
      the curcumin analog, C3, may be a more promising drug candidate for its potential
      application for the prevention and treatment of eye diseases, such as AMD.

PMID- 23954768
TI  - Nanoparticle release from nano-silver antimicrobial food containers.
AB  - Polymer nanocomposites incorporating metal or metal oxide nanoparticles have been
      developed to improve their characteristics (flexibility, gas barrier properties,
      antimicrobial or antioxidant properties, etc.). Among them silver nanoparticles
      are used because of their antimicrobial effect in many daily life materials, i.e.
      food packaging. However, there is not any reference to the migration of
      nanoparticles to the food. In this paper the results of migration studies (with
      different simulant solutions and times) in three commercial nanosilver plastic
      food containers are shown. Migration solutions were evaluated by ICP-MS and SEM
      EDX analysis and silver in dissolved form and silver as nanoparticles were
      analyzed, a key aspect for the toxicity. Silver migration was observed for all
      samples studied, with the total silver migration values ranging between 1.66 and
      31.46 ng/cm(2) (lower than the permissible limits). Size and morphology of the
      silver nanoparticles changed for the different samples (ranging between 10 and 60
      nm) and migration of other nanosized materials was also confirmed.

PMID- 23954769
TI  - Anti-insulin antibodies interference in the Siemens Immulite chemiluminescent
      insulin immuno-assay.

PMID- 23954770
TI  - Utility of cystatin C as a marker for the severity of aortic regurgitation in
      hypertensive patients.
AB  - BACKGROUND: Cystatin C, a cathepsin inhibitor, is involved in the remodeling of
      human aortic valve and left ventricle (LV). OBJECTIVE: Cystatin C may be related
      to the severity of aortic regurgitation (AR). METHODS: We measured cystatin C and
      CRP in hypertensive patients with mild-to-moderate AR (n=120) and in those
      without AR (n=128). Echocardiography was performed to assess the vena contracta
      width (the narrowest region of regurgitant jet, VCW) as a marker of the severity
      of AR, relative wall thickness as a marker of LV concentric remodeling, and the
      ratio of early peak mitral flow to early diastolic mitral annular velocity (E/e')
      as an index of LV diastolic function. Glomerular filtration rate (GFR) was
      estimated using the MDRD methods. RESULTS: Cystatin C levels were greater in
      hypertensive patients with AR than in those without AR. A multiple linear
      regression analysis indicated cystatin C levels correlated with the VCW
      independent of GFR, body mass index, CRP, relative wall thickness, and E/e' in
      hypertensive patients with AR. CONCLUSIONS: Cystatin C was associated with the
      severity of regurgitation independent of renal function body composition chronic
      inflammation LV remodeling and diastolic function in hypertensive patients with
      mild-to-moderate AR.

PMID- 23954771
TI  - Alpha-fetoprotein-L3 in hepatocellular carcinoma: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Alpha-fetoprotein (AFP) has been widely used as a
      diagnostic marker. AFP is also increased in patients at high risk for
      hepatocellular carcinoma (HCC), ie those with chronic hepatitis. The percentage
      of lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3%) has long been
      proposed as a marker for HCC, but has not been widely adopted due to inconsistent
      results reported in the literature. In this study, the performance of AFP-L3% is
      specifically evaluated for diagnosis of HCC. METHODS: A systematic review of
      relevant studies, the sensitivity, specificity, and diagnostic odds ratio (DOR)
      for the diagnosis of HCC were pooled using random-effects models. The overall
      test performance was summarized using summary receiver operating characteristic
      (SROC) curve analysis. Potential between-study heterogeneity was explored by meta
      regression model. RESULTS: Twelve articles were included in this meta-analysis.
      The overall estimates of AFP-L3% in detecting HCC were as follows: pooled
      sensitivity, 0.483 (95% confidence interval (CI) 0.459-0.507); pooled
      specificity, 0.929 (95% CI 0.916-0.940); DOR, 12.33 (95% CI 7.82-19.44); and area
      under the curve (AUC), 0.7564. CONCLUSIONS: AFP-L3% could be complementary to AFP
      as a marker for HCC.

PMID- 23954772
TI  - A case of IgD myeloma representing a missed biclonal paraproteinemia or isotype
      switch in a patient previously diagnosed with IgA-lambda myeloma.
AB  - BACKGROUND: Multiple myeloma is a clonal plasma cell neoplasm that is identified
      in the laboratory by a presence of a monoclonal immunoglobulin or increased
      plasma light chain levels. METHODS: The most commonly identified and tested
      immunoglobulins are IgA, IgG and IgM. RESULTS: Rare cases of multiple myeloma
      present with monoclonal IgD and IgE paraproteins. CONCLUSION: We present a case
      of IgD myeloma diagnosed in a patient who had achieved partial remission from a
      previously diagnosed IgA myeloma, possibly representing a missed biclonal
      paraproteinemia or isotype switch after treatment.

PMID- 23954773
TI  - Analysis of the raw serum peptidomic pattern in glioma patients.
AB  - BACKGROUND: Glioma is a common and lethal type of brain tumor. Serum peptides
      reflected the pathological changes of the body. Here we studied the serum peptide
      profiles to distinguish glioma disease and measure glioma staging. METHODS: Serum
      peptides were captured by WCX magnetic beads and were analyzed by MALDI-TOF mass
      spectrometer. Sera from 53 glioma patients and 69 age-matched healthy controls
      were analyzed. Clinpro Tools software was used to obtain a common peak m/z list
      from all measured samples. An optimal subset of peptides was selected to
      establish a predictive classification model with the newly developed competitive
      adaptive reweighted sampling (CARS) variable selection method. Serum peptide
      profiles were classified through a partial least-squares-linear discriminate
      analysis (PLS-LDA). We also searched for progressively different peptide peaks
      that correlated with an increasing malignancy of glioma. RESULTS: The following
      pattern recognition equation was established with selected peptide signals: Y=
      0.1113-0.113X1-0.2916X2+0.1128X3-0.2057X4-0.2047X5-0.3048X6+0.2835X7+0.3121X8
      0.1458X9+0.0354X10-0.2022X11. Using this pattern, classification sensitivity and
      specificity achieved were 0.9057 and 0.9855, respectively. Additionally, we
      detected 3 peptide signals that correlated with glioma grade. Among these, the
      intensity of peak 2082.32 Da correlated positively with the glioma progressing,
      and peaks with sizes of 3316.08 Da and 6631.45 Da show a decreasing intensity
      with increasing glioma grade. CONCLUSIONS: 11 peptide recognition patterns and
      specific peak intensities might be useful for the early detection and tumor
      staging of glioma, but they need to be further validated and evaluated
      independently in clinical settings.

PMID- 23954775
TI  - The role of urinary neutrophil gelatinase-associated lipocalin in lupus
      nephritis.
AB  - BACKGROUND: Urine neutrophil gelatinase-associated lipocalin (uNGAL) has been
      proposed as a potential biomarker for lupus nephritis (LN) activity. We
      determined the association between uNGAL with LN activity in systemic lupus
      erythematosus (SLE) patients compared to the current standard markers of SLE.
      METHODS: A total of 100 SLE patients with biopsy-proven LN were recruited-47 with
      active and 53 inactive LN. uNGAL levels were measured. Renal function test,
      urinary parameters, lupus serology and calculated renal SLE Disease Activity
      Index-2K (renal SLEDAI-2K) were analyzed to determine their associations with
      uNGAL. RESULTS: Normalized uNGAL levels (ng/mg creatinine) were significantly
      higher in patients with active LN compared to those with inactive disease
      (p=0.01). uNGAL and renal SLEDAI-2K were associated (r=0.32, p=0.001). Multiple
      logistic regression showed that only serum creatinine and renal SLEDAI-2K were
      independent predictors of uNGAL levels (p=0.03 and 0.02 respectively). Analysis
      of the receiver operating characteristic (ROC) curve showed that uNGAL was a
      potential biomarker for LN. CONCLUSIONS: uNGAL was increased in active LN
      especially in LN flares. Serial measurements of uNGAL levels may be of value in
      monitoring response of LN to treatment and for predicting LN flares.

PMID- 23954774
TI  - Articular osteochondrosis: a comparison of naturally-occurring human and animal
      disease.
AB  - BACKGROUND: Osteochondrosis (OC) is a common developmental orthopedic disease
      affecting both humans and animals. Despite increasing recognition of this disease
      among children and adolescents, its pathogenesis is incompletely understood
      because clinical signs are often not apparent until lesions have progressed to
      end-stage, and examination of cadaveric early lesions is not feasible. In
      contrast, both naturally-occurring and surgically-induced animal models of
      disease have been extensively studied, most notably in horses and swine, species
      in which OC is recognized to have profound health and economic implications. The
      potential for a translational model of human OC has not been recognized in the
      existing human literature. OBJECTIVE: The purpose of this review is to highlight
      the similarities in signalment, predilection sites and clinical presentation of
      naturally-occurring OC in humans and animals and to propose a common pathogenesis
      for this condition across species. STUDY DESIGN: Review. METHODS: The published
      human and veterinary literature for the various manifestations of OC was
      reviewed. Peer-reviewed original scientific articles and species-specific review
      articles accessible in PubMed (US National Library of Medicine) were eligible for
      inclusion. RESULTS: A broad range of similarities exists between OC affecting
      humans and animals, including predilection sites, clinical presentation,
      radiographic/MRI changes, and histological appearance of the end-stage lesion,
      suggesting a shared pathogenesis across species. CONCLUSION: This proposed shared
      pathogenesis for OC between species implies that naturally-occurring and
      surgically-induced models of OC in animals may be useful in determining risk
      factors and for testing new diagnostic and therapeutic interventions that can be
      used in humans.

PMID- 23954776
TI  - Sports doping: emerging designer and therapeutic beta2-agonists.
AB  - Beta2-adrenergic agonists, or beta2-agonists, are considered essential
      bronchodilator drugs in the treatment of bronchial asthma, both as symptom
      relievers and, in combination with inhaled corticosteroids, as disease
      controllers. The use of beta2-agonists is prohibited in sports by the World Anti
      Doping Agency (WADA) due to claimed anabolic effects, and also, is prohibited as
      growth promoters in cattle fattening in the European Union. This paper reviews
      the last seven-year (2006-2012) literature concerning the development of novel
      beta2-agonists molecules either by modifying the molecule of known beta2-agonists
      or by introducing moieties producing indole-, adamantyl- or phenyl urea
      derivatives. New emerging beta2-agonists molecules for future therapeutic use are
      also presented, intending to emphasize their potential use for doping purposes or
      as growth promoters in the near future. 

PMID- 23954777
TI  - Clarity versus complexity: land-use modeling as a practical tool for decision
      makers.
AB  - The last decade has seen a remarkable increase in the number of modeling tools
      available to examine future land-use and land-cover (LULC) change. Integrated
      modeling frameworks, agent-based models, cellular automata approaches, and other
      modeling techniques have substantially improved the representation of complex
      LULC systems, with each method using a different strategy to address complexity.
      However, despite the development of new and better modeling tools, the use of
      these tools is limited for actual planning, decision-making, or policy-making
      purposes. LULC modelers have become very adept at creating tools for modeling
      LULC change, but complicated models and lack of transparency limit their utility
      for decision-makers. The complicated nature of many LULC models also makes it
      impractical or even impossible to perform a rigorous analysis of modeling
      uncertainty. This paper provides a review of land-cover modeling approaches and
      the issues causes by the complicated nature of models, and provides suggestions
      to facilitate the increased use of LULC models by decision-makers and other
      stakeholders. The utility of LULC models themselves can be improved by 1)
      providing model code and documentation, 2) through the use of scenario frameworks
      to frame overall uncertainties, 3) improving methods for generalizing key LULC
      processes most important to stakeholders, and 4) adopting more rigorous standards
      for validating models and quantifying uncertainty. Communication with decision
      makers and other stakeholders can be improved by increasing stakeholder
      participation in all stages of the modeling process, increasing the transparency
      of model structure and uncertainties, and developing user-friendly decision
      support systems to bridge the link between LULC science and policy. By
      considering these options, LULC science will be better positioned to support
      decision-makers and increase real-world application of LULC modeling results. 

PMID- 23954778
TI  - Thoracoscopic water pleurectomy for the treatment of recurrent spontaneous
      pneumothorax.
AB  - We describe a new technique for thoracoscopic pleurectomy for the treatment of
      spontaneous pneumothorax. This is performed by percutaneous subpleural
      infiltration of 0.9% saline solution from the second to the seventh or eighth
      intercostal space, the so-called water pleurectomy. The extrapleural infiltration
      allows gentle separation of the parietal pleura by the division of its natural
      adherence to the endothoracic fascia. This technique reduces the trauma of the
      procedure and decreases bleeding. Technical details and preliminary results are
      reported. 

PMID- 23954779
TI  - In situ demonstration of Fluoro-Turquoise conjugated gelatin for visualizing
      brain vasculature and endothelial cells and their characterization in normal and
      kainic acid exposed animals.
AB  - The present study describes a new method for the visualization of the vasculature
      lumen and endothelial cells and characterizes their morphology in the brains of
      normal and kainic acid (KA) treated rats. Herein, labeling was accomplished using
      Fluoro-Turquoise (FT), a novel reactive blue fluorochrome conjugated to gelatin.
      Strong blue fluorescence was observed throughout the brain vasculature following
      intra-cardiac perfusion with FT-gel in normal animals. However, in the brains of
      KA treated rats (hippocampus, midline and ventral thalamus, piriform cortex), the
      vascular lumen was typically constricted, sclerotic and only faintly stained. The
      advantages of FT-gel over other markers can be attributed to its unique chemical
      and spectral properties. Specifically, Fluoro-Turquoise is a very bright blue UV
      excitable dye that does not bleed through when visualized using other filters,
      making it ideal for multiple immunofluorescent labeling studies. Its brightness
      at low magnification also makes it ideal for low magnification whole brain
      imaging. Compared to alternative techniques for visualizing blood vessels, such
      as India ink, fluorescent dye-conjugated dextran, the corrosion technique,
      endothelial cell markers and lectins, the present method results in excellent
      visualization of blood vessels. 

PMID- 23954781
TI  - Rationally designed nanovehicles to overcome cancer chemoresistance.
AB  - Drug resistance is a primary hindrance towards curative cancer chemotherapy.
      Nanotechnology holds great promise in establishing efficacious and innovative
      strategies to overcome chemoresistance, and markedly facilitate complementary
      treatments and cancer diagnostics. Various nanomedical devices are being
      introduced and evaluated, demonstrating encouraging results. While stealth
      liposomes serve as a benchmark, astonishing progress is witnessed in polymeric
      nanovehicles, sometimes combined with low molecular weight surfactants, some of
      which inhibit drug resistance in addition to solubilizing drugs. Cutting edge
      multifunctional or quadrugnostic nanoparticles currently developed offer
      simultaneous targeted delivery of chemotherapeutics and chemosensitizers or drug
      resistance gene silencing cargo, along with diagnostic imaging agents, like
      metallic NPs. Viral and cellular components offer exciting new routes for cancer
      targeting and treatment. Targeting intracellular compartments is another
      challenging frontier spawning pioneering approaches and results. To further
      enhance rational design of nanomedicine for overcoming drug resistance, we review
      the latest thoughts and accomplishments in recent literature.

PMID- 23954780
TI  - Classification of methods in transcranial electrical stimulation (tES) and
      evolving strategy from historical approaches to contemporary innovations.
AB  - Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive
      current application to the brain used in research and clinical practice. We
      present the first comprehensive and technical review, explaining the evolution of
      tES in both terminology and dosage over the past 100 years of research to present
      day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as
      Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through
      Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET),
      and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial
      Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through
      Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in
      interest, variations of transcranial Direct Current Stimulation were explored
      intermittently, including Polarizing current, Galvanic Vestibular Stimulation
      (GVS), and Transcranial Micropolarization. The development of these approaches
      alongside Electroconvulsive Therapy (ECT) and pharmacological developments are
      considered. Both the roots and unique features of contemporary approaches such as
      transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise
      Stimulation (tRNS) are discussed. Trends and incremental developments in
      electrode montage and waveform spanning decades are presented leading to the
      present day. Commercial devices, seminal conferences, and regulatory decisions
      are noted. We conclude with six rules on how increasing medical and technological
      sophistication may now be leveraged for broader success and adoption of tES. 

PMID- 23954782
TI  - XIAP regulates caspase activity in degenerating axons.
AB  - Our knowledge of the destructive events that regulate axonal degeneration is
      rudimentary. Here, we examine the role of caspases and their endogenous
      inhibitor, the X-linked inhibitor of apoptosis protein (XIAP), in axonal
      degeneration of dorsal root ganglion (DRG) axons. We show that caspase-3, caspase
      6, and caspase-9 are present in axons and are cleaved upon nerve growth factor
      (NGF) withdrawal. We observed that caspase-3 activity is high in NGF-withdrawn
      axons and that CASP3(-/-) axons are protected from degeneration. XIAP(-/-) DRG
      sensory neurons degenerate more rapidly and contain more active caspase-3 than
      their wild-type counterparts, indicating that axonal caspases are normally
      regulated by XIAP. Importantly, axonal XIAP levels drop sharply after NGF
      withdrawal; if XIAP levels are maintained by overexpression, axonal caspase-3
      activation and axonal degeneration are suppressed. Finally, we show that XIAP(-/
      ) embryos have stunted dermal innervation. We propose that XIAP-mediated caspase
      inhibition plays an important role in regulating morphogenic events that shape
      the nervous system during development. 

PMID- 23954783
TI  - The tetraspanin CD9 affords high-purity capture of all murine hematopoietic stem
      cells.
AB  - Prospective isolation is critical for understanding the cellular and molecular
      aspects of stem cell heterogeneity. Here, we identify the cell surface antigen
      CD9 as a positive marker that provides a simple alternative for hematopoietic
      stem cell isolation at high purity. Crucially, CD9 affords the capture of all
      hematopoietic stem cells in murine bone marrow in the absence of contaminating
      populations that lack authentic stem cell function. Using CD9 as a tool to
      subdivide hematopoietic stem-cell-containing populations, we provide evidence for
      heterogeneity at the cellular, functional, and molecular levels. 

PMID- 23954784
TI  - The calcineurin-NFAT-angiopoietin-2 signaling axis in lung endothelium is
      critical for the establishment of lung metastases.
AB  - The premetastatic niche is a predetermined site of metastases, awaiting the
      influx of tumor cells. However, the regulation of the angiogenic switch at these
      sites has not been examined. Here, we demonstrate that the calcineurin and
      nuclear factor of activated T cells (NFAT) pathway is activated specifically in
      lung endothelium prior to the detection of tumor cells that preferentially
      metastasize to the lung. Upregulation of the calcineurin pathway via deletion of
      its endogenous inhibitor Dscr1 leads to a significant increase in lung metastases
      due to increased expression of a newly identified NFAT target, Angiopoietin-2
      (ANG2). Increased VEGF levels specifically in the lung, and not other organ
      microenvironments, trigger a threshold of calcineurin-NFAT signaling that
      transactivates Ang2 in lung endothelium. Further, we demonstrate that
      overexpression of DSCR1 or the ANG2 receptor, soluble TIE2, prevents the
      activation of lung endothelium, inhibiting lung metastases in our mouse models.
      Our studies provide insights into mechanisms underlying angiogenesis in the
      premetastatic niche and offer targets for lung metastases. 

PMID- 23954785
TI  - Muscle cells provide instructions for planarian regeneration.
AB  - Regeneration requires both potential and instructions for tissue replacement. In
      planarians, pluripotent stem cells have the potential to produce all new tissue.
      The identities of the cells that provide regeneration instructions are unknown.
      Here, we report that position control genes (PCGs) that control regeneration and
      tissue turnover are expressed in a subepidermal layer of nonneoblast cells. These
      subepidermal cells coexpress many PCGs. We propose that these subepidermal cells
      provide a system of body coordinates and positional information for regeneration,
      and identify them to be muscle cells of the planarian body wall. Almost all
      planarian muscle cells express PCGs, suggesting a dual function: contraction and
      control of patterning. PCG expression is dynamic in muscle cells after injury,
      even in the absence of neoblasts, suggesting that muscle is instructive for
      regeneration. We conclude that planarian regeneration involves two highly
      flexible systems: pluripotent neoblasts that can generate any new cell type and
      muscle cells that provide positional instructions for the regeneration of any
      body region. 

PMID- 23954786
TI  - Clathrin-mediated endocytosis persists during unperturbed mitosis.
AB  - How does mitosis influence the critical process of endocytosis? Some experiments
      lead to the conclusion that endocytosis arrests completely during mitosis,
      whereas others indicate that endocytosis persists. We have resolved this apparent
      discrepancy by showing how conditions of the experiment influence its outcome.
      The dynamics of clathrin-coated pit formation and the uptake of transferrin are
      maintained in naturally dividing cells but are nearly absent in mitotic cells
      arrested chemically by treatment with nocodazole, S-Trityl-L-cysteine, or RO
      3306. Moreover, sequentially incubating cells at 4 degrees C and then shifting
      them to 37 degrees C or to serum starvation artificially increases the amount of
      transferrin receptor at the surface of naturally dividing cells, leading to the
      incorrect conclusion that endocytosis has ceased during mitosis. Thus, our data
      show that endocytosis is unaffected during all stages of natural cell division. 

PMID- 23954787
TI  - Convergent evolution of hyperswarming leads to impaired biofilm formation in
      pathogenic bacteria.
AB  - Most bacteria in nature live in surface-associated communities rather than
      planktonic populations. Nonetheless, how surface-associated environments shape
      bacterial evolutionary adaptation remains poorly understood. Here, we show that
      subjecting Pseudomonas aeruginosa to repeated rounds of swarming, a collective
      form of surface migration, drives remarkable parallel evolution toward a
      hyperswarmer phenotype. In all independently evolved hyperswarmers, the
      reproducible hyperswarming phenotype is caused by parallel point mutations in a
      flagellar synthesis regulator, FleN, which locks the naturally monoflagellated
      bacteria in a multiflagellated state and confers a growth rate-independent
      advantage in swarming. Although hyperswarmers outcompete the ancestral strain in
      swarming competitions, they are strongly outcompeted in biofilm formation, which
      is an essential trait for P. aeruginosa in environmental and clinical settings.
      The finding that evolution in swarming colonies reliably produces evolution of
      poor biofilm formers supports the existence of an evolutionary trade-off between
      motility and biofilm formation. 

PMID- 23954788
TI  - Obesity promotes liver carcinogenesis via Mcl-1 stabilization independent of IL
      6Ralpha signaling.
AB  - Obesity increases the incidence of hepatocellular carcinoma (HCC) development in
      part through the activation of obesity-associated proinflammatory signaling.
      Here, we show that in lean mice, abrogation of IL-6Ralpha signaling protects
      against diethylnitrosamine (DEN)-induced HCC development. HCC protection occurs
      via Mcl-1 destabilization, thus promoting hepatocyte apoptosis. IL-6 regulates
      Mcl-1 stability via the inhibition of PP-1alpha expression, promoting GSK-3beta
      inactivation. In addition, IL-6 suppresses expression of the Mcl-1 E3 ligase
      (Mule). Consequently, IL-6Ralpha deficiency activates PP-1alpha and Mule
      expression, resulting in increased Mcl-1 turnover and protection against HCC
      development. In contrast, in obesity, inhibition of PP-1alpha and Mule
      expression, leading to Mcl-1 stabilization, occurs independently of IL-6
      signaling. Collectively, this study provides evidence that obesity inhibits
      hepatocyte apoptosis through Mcl-1 stabilization independent of IL-6 signaling,
      thus promoting liver carcinogenesis. 

PMID- 23954789
TI  - Glycine receptor alpha2 subunit activation promotes cortical interneuron
      migration.
AB  - Glycine receptors (GlyRs) are detected in the developing CNS before
      synaptogenesis, but their function remains elusive. This study demonstrates that
      functional GlyRs are expressed by embryonic cortical interneurons in vivo.
      Furthermore, genetic disruption of these receptors leads to interneuron migration
      defects. We discovered that extrasynaptic activation of GlyRs containing the
      alpha2 subunit in cortical interneurons by endogenous glycine activates voltage
      gated calcium channels and promotes calcium influx, which further modulates
      actomyosin contractility to fine-tune nuclear translocation during migration.
      Taken together, our data highlight the molecular events triggered by GlyR alpha2
      activation that control cortical tangential migration during embryogenesis. 

PMID- 23954790
TI  - Lysine succinylation is a frequently occurring modification in prokaryotes and
      eukaryotes and extensively overlaps with acetylation.
AB  - Recent studies have shown that lysines can be posttranslationally modified by
      various types of acylations. However, except for acetylation, very little is
      known about their scope and cellular distribution. We mapped thousands of
      succinylation sites in bacteria (E. coli), yeast (S. cerevisiae), human (HeLa)
      cells, and mouse liver tissue, demonstrating widespread succinylation in diverse
      organisms. A majority of succinylation sites in bacteria, yeast, and mouse liver
      were acetylated at the same position. Quantitative analysis of succinylation in
      yeast showed that succinylation was globally altered by growth conditions and
      mutations that affected succinyl-coenzyme A (succinyl-CoA) metabolism in the
      tricarboxylic acid cycle, indicating that succinylation levels are globally
      affected by succinyl-CoA concentration. We preferentially detected succinylation
      on abundant proteins, suggesting that succinylation occurs at a low level and
      that many succinylation sites remain unidentified. These data provide a systems
      wide view of succinylation and its dynamic regulation and show its extensive
      overlap with acetylation. 

PMID- 23954791
TI  - Role of the mixed-lineage protein kinase pathway in the metabolic stress response
      to obesity.
AB  - Saturated free fatty acid (FFA) is implicated in the metabolic response to
      obesity. In vitro studies indicate that FFA signaling may be mediated by the
      mixed-lineage protein kinase (MLK) pathway that activates cJun NH2-terminal
      kinase (JNK). Here, we examined the role of the MLK pathway in vivo using a mouse
      model of diet-induced obesity. The ubiquitously expressed MLK2 and MLK3 protein
      kinases have partially redundant functions. We therefore compared wild-type and
      compound mutant mice that lack expression of MLK2 and MLK3. MLK deficiency
      protected mice against high-fat-diet-induced insulin resistance and obesity.
      Reduced JNK activation and increased energy expenditure contribute to the
      metabolic effects of MLK deficiency. These data confirm that the MLK pathway
      plays a critical role in the metabolic response to obesity. 

PMID- 23954792
TI  - Adenosine prevents isoprenaline-induced cardiac contractile and
      electrophysiological dysfunction.
AB  - Excessive levels of catecholamines are believed to contribute to cardiac
      dysfunction in a variety of disease states, including myocardial infarction and
      heart failure, and are particularly implicated in stress-induced cardiomyopathy,
      an increasingly recognized cardiomyopathy associated with significant morbidity
      and mortality. We have previously shown that a high dose of isoprenaline induces
      reversible regional dysfunction of the left ventricle in mice. We now hypothesize
      that adenosine can prevent cardiac dysfunction in this mouse model of stress
      induced cardiomyopathy. Hundred male C57BL/6 mice were injected with 400mg/kg
      isoprenaline and then randomized to either 400mg/kg adenosine or saline. Cardiac
      function was evaluated by echocardiography at baseline and 2, 24, 48, 72, 96 and
      120 min post isoprenaline. Myocardial fibrosis was quantified after 10 days.
      Intracellular lipid accumulation was quantified after 2 and 24h.
      Electrophysiological parameters and degree of lipid accumulation were evaluated
      in cultured HL1 cardiomyocytes. Two hours post isoprenaline treatment,
      echocardiographic parameters of global and posterior wall regional function were
      significantly better in adenosine-treated mice (P<0.05). This difference
      persisted at 24h, but saline-treated mice gradually recovered over the next 96 h.
      Intracellular lipid accumulation was also significantly lower in adenosine mice.
      We found no sign of fibrosis in the adenosine mice, whereas the extent of
      fibrosis in isoprenaline mice was 1.3% (P<0.05). Furthermore, adenosine-treated
      HL1 cells showed preserved electrophysiological function and displayed less
      severe intracellular lipid accumulation in response to isoprenaline. In
      conclusion, adenosine attenuates isoprenaline-induced cardiac dysfunction in mice
      and cells.

PMID- 23954793
TI  - High dose remifentanil increases myocardial oxidative stress and compromises
      remifentanil infarct-sparing effects in rats.
AB  - Chronic administration of high dose opioids such as morphine is known to create
      intracellular oxidative stress via an opioid receptor dependent mechanism and
      this can interfere with cellular function. This study aimed at examining whether
      such changes can occur following short term exposure to high concentration of
      remifentanil, a potent short acting opioid. We conducted a experimental study
      using rat myocardium and systematically quantified tissue levels of superoxide
      anions, malondialdehyde (MDA) and nitrotyrosine following exposure to increasing
      duration (15 min, 1 or 2 h) or escalating doses of remifentanil (1 MUg, 5 MUg, 10
      MUg or 20 MUg/kg/min). Concurrently the susceptibility of the heart to ischaemia
      reperfusion injury was assessed under the similar conditions. For any given
      duration of remifentanil infusion, there was increasing superoxide anions
      generated as the dose of remifentanil was increased. MDA concentrations were
      significantly increased when the animal was exposed to 10 MUg/kg/min for 2h or 20
      MUg/kg/min for any duration. There was a trend towards an increased nitrotyrosine
      concentration with increasing dose of remifentanil, becoming significant when the
      dose was 20 MUg/kg/min. The infarct limiting ability of remifentanil was
      compromised when the dihydroethidium fluorescence positive cell percentage
      exceeded 50%, MDA concentration greater than 2 nmol/mg of protein and
      nitrotyrosine content exceeding 1.5 MUg/mg of protein. Short term high dose
      opioid exposure can induce oxidative changes seen previously only with chronic
      opioid use and this high oxidative stress environment corrupts the heart's
      sensitivity to be preconditioned by opioids.

PMID- 23954794
TI  - Identify the key amino acid of BAFF binding with TACI.
AB  - B-cell activating factor (BAFF) has been used as a therapeutic target. To develop
      BAFF-specific small molecular inhibitors, it is necessary to know the key amino
      acid in the BAFF binding with its receptor. The key binding amino acid of BAFF
      interacting with its receptor TACI (trans-membrane activator and calcium
      modulator and cyclophilin ligand interactor) was analyzed based on the computer
      guided molecular modeling method. According to theoretical prediction, a series
      of key amino acid mutants of BAFF, including M204 (Lys(204) to Ala), M208
      (Met(208) to Ala), M209 (Gly(209) to Ala), M210 (His(210) to Ala), M234 (Gln(234)
      to Ala), M236 (Met(236) to Ala), and M237 (Pro(237) to Ala) were designed and
      evaluated with biological experiments. The results show that M208, M209, M236,
      and M237 of BAFF were the key amino acids and in accord with the theoretical
      results. The results highlight clues for the further development of BAFF-specific
      small molecular inhibitors. 

PMID- 23954795
TI  - The effects of age and viral serology on gammadelta T-cell numbers and exercise
      responsiveness in humans.
AB  - gammadelta T-cells are cytotoxic effector cells that preferentially migrate to
      peripheral tissues and recognize many types of antigen. We examined the effects
      of age and viral serology on the exercise responsiveness of gammadelta T-cells.
      Blood was collected from 17 younger (age: 23-35yrs) and 17 older (50-64yrs)
      healthy males matched for cytomegalovirus (CMV), Epstein-Barr virus, herpes
      simplex virus-1 and Parvovirus B19 serologic status before and after a single
      bout of cycling exercise. Older had lower numbers and proportions of gammadelta T
      cells than younger, while CMV was associated with increased numbers and
      proportions of gammadelta T-cells in younger but not older. Exercise evoked a ~2
      fold increase in circulating gammadelta T-cell numbers. The magnitude of this
      response was 3-times greater in younger compared to older, and 1.6-times greater
      in younger CMV-infected compared to younger non CMV-infected. To conclude,
      gammadelta T-cell numbers and exercise responsiveness decreases with age and may
      contribute to impaired immunosurveillance after acute acute physical stress. 

PMID- 23954797
TI  - Isolation and characterization of FLOWERING LOCUS T subforms and APETALA1 of the
      subtropical fruit tree Dimocarpus longan.
AB  - Longan (Dimocarpus longan Lour.) is a subtropical evergreen fruit tree, mainly
      cultivated in Asia. Two putative floral integrator genes, D. longan FLOWERING
      LOCUS T1 and 2 (DlFT1 and DlFT2) were isolated and both translated sequences
      revealed a high homology to FT sequences from other plants. Moreover, two
      APETALA1-like (DlAP1-1 and DlAP1-2) sequences from longan were isolated and
      characterized. Results indicate that the sequences of these genes are highly
      conserved, suggesting functions in the longan flowering pathway. Ectopic
      expression of the longan genes in arabidopsis resulted in different flowering
      time phenotypes of transgenic plants. Expression experiments reveal a different
      action of the longan FT genes and indicate that DlFT1 is a flowering promoter,
      while DlFT2 acts as flowering inhibitor. Overexpression of longan AP1 genes in
      transgenic arabidopsis results in a range of flowering time phenotypes also
      including early and late flowering individuals. 

PMID- 23954796
TI  - Hepatic extracellular signal-regulated kinase 2 suppresses endoplasmic reticulum
      stress and protects from oxidative stress and endothelial dysfunction.
AB  - BACKGROUND: Insulin signaling comprises 2 major cascades: the insulin receptor
      substrate/phosphatidylinositol 3'-kinase/protein kinase B and Ras/Raf/mitogen
      activated protein kinase/kinase/ERK pathways. While many studies on the tissue
      specific effects of the insulin receptor substrate/phosphatidylinositol 3' 
      kinase/protein kinase B pathway have been conducted, the role of the other
      cascade in tissue-specific insulin resistance has not been investigated. High
      glucose/fatty acid toxicity, inflammation, and oxidative stress, all of which are
      associated with insulin resistance, can activate ERK. The liver plays a central
      role in metabolism, and hepatosteatosis is associated with vascular diseases. The
      aim of study was to elucidate the role of hepatic ERK2 in hepatosteatosis,
      metabolic remodeling, and endothelial dysfunction. METHODS AND RESULTS: We
      created liver-specific ERK2 knockout mice and fed them with a high-fat/high
      sucrose diet for 20 weeks. The high-fat/high-sucrose diet-fed liver-specific ERK2
      knockout mice exhibited a marked deterioration in hepatosteatosis and metabolic
      remodeling represented by impairment of glucose tolerance and decreased insulin
      sensitivity without changes in body weight, blood pressure, and serum
      cholesterol/triglyceride levels. In the mice, endoplasmic reticulum stress was
      induced together with decreased mRNA and protein expressions of hepatic
      sarco/endoplasmic reticulum Ca(2+)-ATPase 2. In a hepatoma cell line, inhibition
      of ERK activation- induced endoplasmic reticulum stress only in the presence of
      palmitate. Vascular reactive oxygen species were elevated with upregulation of
      nicotinamide adenine dinucleotide phosphate oxidase1 (Nox1) and Nox4 and
      decreased phosphorylation of endothelial nitric oxide synthase, which resulted in
      the remarkable endothelial dysfunction in high-fat/high-sucrose diet-fed liver
      specific ERK2 knockout mice. CONCLUSIONS: Hepatic ERK2 suppresses endoplasmic
      reticulum stress and hepatosteatosis in vivo, which results in protection from
      vascular oxidative stress and endothelial dysfunction. These findings demonstrate
      a novel role of hepatic ERK2 in obese-induced insulin resistance in the
      protection from hepatovascular metabolic remodeling and vascular diseases.

PMID- 23954799
TI  - Ubiquitin in the peroxisomal protein import pathway.
AB  - PEX5 is the shuttling receptor for newly synthesized peroxisomal matrix proteins.
      Alone, or with the help of an adaptor protein, this receptor binds peroxisomal
      matrix proteins in the cytosol and transports them to the peroxisomal membrane
      docking/translocation module (DTM). The interaction between cargo-loaded PEX5 and
      the DTM ultimately results in its insertion into the DTM with the concomitant
      translocation of the cargo protein across the organelle membrane. PEX5 is not
      consumed in this event; rather it is dislocated back into the cytosol so that it
      can promote additional rounds of protein transportation. Remarkably, the data
      collected in recent years indicate that dislocation is preceded by
      monoubiquitination of PEX5 at a conserved cysteine residue. This mandatory
      modification is not the only type of ubiquitination occurring at the DTM. Indeed,
      several findings suggest that defective receptors jamming the DTM are
      polyubiquitinated and targeted to the proteasome for degradation. 

PMID- 23954800
TI  - Site directed mutagenesis of StSUT1 reveals target amino acids of regulation and
      stability.
AB  - Plant sucrose transporters (SUTs) are functional as sucrose-proton-cotransporters
      with an optimal transport activity in the acidic pH range. Recently, the pH
      optimum of the Solanum tuberosum sucrose transporter StSUT1 was experimentally
      determined to range at an unexpectedly low pH of 3 or even below. Various
      research groups have confirmed these surprising findings independently and in
      different organisms. Here we provide further experimental evidence for a pH
      optimum at physiological extrema. Site directed mutagenesis provides information
      about functional amino acids, which are highly conserved and responsible for this
      extraordinary increase in transport capacity under extreme pH conditions. Redox
      dependent dimerization of the StSUT1 protein was described earlier. Here the
      ability of StSUT1 to form homodimers was demonstrated by heterologous expression
      in Lactococcus lactis and Xenopus leavis using Western blots, and in plants by
      bimolecular fluorescence complementation. Mutagenesis of highly conserved
      cysteine residues revealed their importance in protein stability. The
      accessibility of regulatory amino acid residues in the light of StSUT1's
      compartmentalization in membrane microdomains is discussed.

PMID- 23954798
TI  - Mitochondrial translation initiation machinery: conservation and diversification.
AB  - The highly streamlined mitochondrial genome encodes almost exclusively a handful
      of transmembrane components of the respiratory chain complex. In order to ensure
      the correct assembly of the respiratory chain, the products of these genes must
      be produced in the correct stoichiometry and inserted into the membrane, posing a
      unique challenge to the mitochondrial translational system. In this review we
      describe the proteins orchestrating mitochondrial translation initiation:
      bacterial-like general initiation factors mIF2 and mIF3, as well as mitochondria
      specific components - mRNA-specific translational activators and mRNA-nonspecific
      accessory initiation factors. We consider how the fast rate of evolution in these
      organelles has not only created a system that is divergent from that of its
      bacterial ancestors, but has led to a huge diversity in lineage specific
      mechanistic features of mitochondrial translation initiation among eukaryotes. 

PMID- 23954801
TI  - Vitamin C facilitates pluripotent stem cell maintenance by promoting pluripotency
      gene transcription.
AB  - Vitamin C has recently received attention because of its ability to improve
      induced pluripotent stem cells (iPSCs) generation [1-3] and maintain a blastocyst
      like state in ES cells [4]. However, the underlying mechanisms are not fully
      understood. In this study, we found that vitamin C maintained the morphology of
      mouse embryonic stem cell (mESC) colonies and inhibited mESC differentiation.
      Gene expression profiling revealed that the genes down-regulated by vitamin C
      were grouped in the regulation of differentiation and development, while most of
      the up-regulated genes were enriched in the regulation of transcription involving
      numerous pluripotency factors, which was further confirmed by real time
      quantitative PCR. For the key pluripotency factor Nanog, vitamin C increased its
      promoter activity and protein level. In addition, pathway screening indicated
      that vitamin C may affect various signaling pathways. Our study provides new
      insights into vitamin C-mediated pluripotency maintenance of mESCs.

PMID- 23954802
TI  - Schwann cell migration and neurite outgrowth are influenced by media conditioned
      by epineurial fibroblasts.
AB  - The regenerative capacity of the peripheral nervous system is largely related to
      Schwann cells undergoing proliferation and migration after injury and forming
      growth-supporting substrates for severed axons. Novel data show that fibroblasts
      to a certain extent regulate the pro-regenerative behavior of Schwann cells. In
      the setting of peripheral nerve injury, the fibroblasts that form the epineurium
      come into close contact with both Schwann cells and peripheral axons, but the
      potential influence on these latter two cell types has not been studied yet. In
      the present study we explored whether culture media, conditioned by epineurial
      fibroblasts can influence Schwann cells and/or neurite outgrowth from dorsal root
      ganglia neurons in vitro. Our data indicate that epineurial fibroblast
      conditioned culture media substantially increase Schwann cell migration and the
      outgrowth of neurites. Schwann cell proliferation remained largely unaffected.
      These same read-out parameters were assayed in a condition where epineurial
      fibroblasts were subjected to stretch-cell-stress, a mechanical stressor that
      plays an important role in traumatic peripheral nerve injuries. Stretch-cell
      stress of epineurial fibroblasts did not further change the positive effects of
      conditioned media on Schwann cell migration and neurite outgrowth. From these
      data we conclude that an as yet unknown pro-regenerative role can be attributed
      to epineurial fibroblasts, implying that such cells may affect the outcome of
      severe peripheral nerve injury. 

PMID- 23954805
TI  - Orbitofrontal cortex inactivation impairs between- but not within-session
      Pavlovian extinction: an associative analysis.
AB  - The orbitofrontal cortex (OFC) is argued to be the neural locus of Pavlovian
      outcome expectancies. Reinforcement learning theories argue that extinction
      learning in Pavlovian procedures is caused by the discrepancy between the
      expected value of the outcome (US) that is elicited by a predictive stimulus
      (CS), and the lack of experienced US. If the OFC represents Pavlovian outcome
      expectancies that are necessary for extinction learning, then disrupting OFC
      function prior to extinction training should impair extinction learning. This was
      tested. In experiment 1, Long Evans rats received infusions of saline or muscimol
      targeting the lateral OFC prior to three appetitive Pavlovian extinction
      sessions. Muscimol infused into the OFC disrupted between-session but not within
      session extinction behaviour. This finding was not due to muscimol infusions
      disrupting the memory consolidation process per se as there was no effect of
      muscimol infusion when administered immediately post session (experiment 2).
      These findings support a role for the OFC in representing outcome expectancies
      that are necessary for learning. A number of ways in which disrupting outcome
      expectancy information might block learning will be discussed in the context of
      traditional associative learning theories and the associative structures they
      depend on. 

PMID- 23954803
TI  - Dopamine D2 and acetylcholine alpha7 nicotinic receptors have subcellular
      distributions favoring mediation of convergent signaling in the mouse ventral
      tegmental area.
AB  - Alpha7 nicotinic acetylcholine receptors (alpha7nAChRs) mediate nicotine-induced
      burst-firing of dopamine neurons in the ventral tegmental area (VTA), a limbic
      brain region critically involved in reward and in dopamine D2 receptor (D2R)
      related cortical dysfunctions associated with psychosis. The known presence of
      alpha7nAChRs and Gi-coupled D2Rs in dopamine neurons of the VTA suggests that
      these receptors are targeted to at least some of the same neurons in this brain
      region. To test this hypothesis, we used electron microscopic immunolabeling of
      antisera against peptide sequences of alpha7nACh and D2 receptors in the mouse
      VTA. Dual D2R and alpha7nAChR labeling was seen in many of the same somata (co
      localization over 97%) and dendrites (co-localization over 49%), where
      immunoreactivity for each of the receptors was localized to endomembranes as well
      as to non-synaptic or synaptic plasma membranes often near excitatory-type
      synapses. In comparison with somata and dendrites, many more small axons and axon
      terminals were separately labeled for each of the receptors. Thus, single-labeled
      axon terminals were predominant for both alpha7nAChR (57.9%) and D2R (89.0%). The
      majority of the immunolabeled axonal profiles contained D2R-immunoreactivity
      (81.6%) and formed either symmetric or asymmetric synapses consistent with
      involvement in the release of both inhibitory and excitatory transmitters. Of 160
      D2R-labeled terminals, 81.2% were presynaptic to dendrites that expressed
      alpha7nAChR alone or together with the D2R. Numerous glial processes inclusive of
      those enveloping either excitatory- or inhibitory-type synapses also contained
      single labeling for D2R (n=152) and alpha7nAChR (n=561). These results suggest
      that classic antipsychotic drugs, all of which block the D2R, may facilitate
      alpha7nAChR-mediated burst-firing by elimination of D2R-dependent inhibition in
      neurons expressing both receptors as well as by indirect pre-synaptic and glial
      mechanisms.

PMID- 23954804
TI  - Neurochemical changes within human early blind occipital cortex.
AB  - Early blindness results in occipital cortex neurons responding to a wide range of
      auditory and tactile stimuli. These changes in tuning properties are accompanied
      by an extensive reorganization of the occipital cortex that includes alterations
      in anatomical structure, neurochemical and metabolic pathways. Although it has
      been established in animal models that neurochemical pathways are heavily
      affected by early visual deprivation, the effects of blindness on these pathways
      in humans is still not well characterized. Here, using (1)H magnetic resonance
      spectroscopy in nine early blind and normally sighted subjects, we find that
      early blindness is associated with higher levels of creatine, choline and myo
      Inositol and indications of lower levels of GABA within the occipital cortex.
      These results suggest that the cross-modal responses associated with early
      blindness may, at least in part, be driven by changes within occipital
      biochemical pathways. 

PMID- 23954806
TI  - Oxidative stress effect on progesterone-induced blocking factor (PIBF) binding to
      PIBF-receptor in lymphocytes.
AB  - Receptor-ligand binding is an essential interaction for biological function.
      Oxidative stress can modify receptors and/or membrane lipid dynamics, thus
      altering cell physiological functions. The aim of this study is to analyze how
      oxidative stress may alter receptor-ligand binding and lipid domain distribution
      in the case of progesterone-induced blocking factor/progesterone-induced blocking
      factor-receptor. For membrane fluidity regionalization analysis of MEC-1
      lymphocytes, two-photon microscopy was used in individual living cells.
      Lymphocytes were also double stained with AlexaFluor647/progesterone-induced
      blocking factor and Laurdan to evaluate -induced blocking factor/progesterone
      induced blocking factor-receptor distribution in the different membrane domains,
      under oxidative stress. A new procedure has been developed which quantitatively
      analyzes the regionalization of a membrane receptor among the lipid domains of
      different fluidity in the plasma membrane. We have been able to establish a new
      tool which detects and evaluates lipid raft clustering from two-photon microscopy
      images of individual living cells. We show that binding of progesterone-induced
      blocking factor to progesterone-induced blocking factor-receptor causes a
      rigidification of plasma membrane which is related to an increase of lipid raft
      clustering. However, this clustering is inhibited under oxidative stress
      conditions. In conclusion, oxidative stress decreases membrane fluidity, impairs
      receptor-ligand binding and reduces lipid raft clustering. 

PMID- 23954807
TI  - The structure and regulation of magnesium selective ion channels.
AB  - The magnesium ion (Mg(2+)) is the most abundant divalent cation within cells. In
      man, Mg(2+)-deficiency is associated with diseases affecting the heart, muscle,
      bone, immune, and nervous systems. Despite its impact on human health, little is
      known about the molecular mechanisms that regulate magnesium transport and
      storage. Complete structural information on eukaryotic Mg(2+)-transport proteins
      is currently lacking due to associated technical challenges. The prokaryotic MgtE
      and CorA magnesium transport systems have recently succumbed to structure
      determination by X-ray crystallography, providing first views of these ubiquitous
      and essential Mg(2+)-channels. MgtE and CorA are unique among known membrane
      protein structures, each revealing a novel protein fold containing distinct
      arrangements of ten transmembrane-spanning alpha-helices. Structural and
      functional analyses have established that Mg(2+)-selectivity in MgtE and CorA
      occurs through distinct mechanisms. Conserved acidic side-chains appear to form
      the selectivity filter in MgtE, whereas conserved asparagines coordinate hydrated
      Mg(2+)-ions within the selectivity filter of CorA. Common structural themes have
      also emerged whereby MgtE and CorA sense and respond to physiologically relevant,
      intracellular Mg(2+)-levels through dedicated regulatory domains. Within these
      domains, multiple primary and secondary Mg(2+)-binding sites serve to staple
      these ion channels into their respective closed conformations, implying that
      Mg(2+)-transport is well guarded and very tightly regulated. The MgtE and CorA
      proteins represent valuable structural templates to better understand the related
      eukaryotic SLC41 and Mrs2-Alr1 magnesium channels. Herein, we review the
      structure, function and regulation of MgtE and CorA and consider these unique
      proteins within the expanding universe of ion channel and transporter structural
      biology. 

PMID- 23954808
TI  - Identification of a novel alternative splicing variant of hemocyanin from shrimp
      Litopenaeus vannamei.
AB  - Recent evidences suggest that invertebrates express families of immune molecules
      with high levels of sequence diversity. Hemocyanin is an important non-specific
      immune molecule present in the hemolymph of both mollusks and arthropods. In the
      present study, we characterized a novel alternative splicing variant of
      hemocyanin (cHE1) from Litopenaeus vannamei that produced mRNA transcript of 2579
      bp in length. The isoform contained two additional sequences of 296 and 267 bp in
      the 5'- and 3'-terminus respectively, in comparison to that of wild type
      hemocyanin (cHE). Sequence of cHE1 shows 100% identity to that of hemocyanin
      genomic DNA (HE, which does not form an open reading frame), suggesting that cHE1
      might be an alternative splicing variant due to intron retention. Moreover, cHE1
      could be detected by RT-PCR from five tissues (heart, gill, stomach, intestine
      and brain), and from shrimps at stages from nauplius to mysis larva. Further,
      cHE1 mRNA transcripts were significantly increased in hearts after 12h of
      infection with Vibrio parahemolyticus or poly I: C, while no significant
      difference in the transcript levels of hepatopancreas cHE was detected in the
      pathogen-treated shrimps during the period. In summary, these studies suggested a
      novel splicing variant of hemocyanin in shrimp, which might be involved in shrimp
      resistance to pathogenic infection.

PMID- 23954809
TI  - A new recombinant immunotoxin hscFv-ETA' demonstrates specific cytotoxicity
      against chronic myeloid leukemia cells in vitro.
AB  - Antibodies against cell surface antigens of tumor have attracted increasing
      attention in immunotherapy for tumor diagnosis and treatment. Recently, we
      constructed a new recombinant immunotoxin for possible clinical application in
      patients with chronic myeloid leukemia (CML). A functional humanized single chain
      variable fragment (hscFv) against CML patient cells was previously obtained from
      an anti-CML cell hybridoma derived monoclonal antibody. By insertion into the
      bacterial vector pWW20, the hscFv was fused with a deletion mutant of Pseudomonas
      exotoxin A (ETA'). Then the fusion fragment was inserted into the bacterial
      vector pET32a(+). After isopropyl beta-d-thiogalactoside (IPTG) induction, the 6*
      His tagged hscFv-ETA' protein was periplasmically expressed and purified by
      Ni(2+)-NTA column. The characteristics of the recombinant protein were assessed
      by cell membrane-ELISA, flow cytometry, and toxicity assays in CML cell lines and
      CML patient cells. The recombinant immunotoxin showed significant toxicity toward
      the CML cell lines K562 and KU812 as tested by MTT and apoptosis assay.
      Approximately 37% of leukemia cells of CML patients were driven into apoptosis by
      hscFv-ETA' as measured by flow cytometric analysis. In conclusion, the hscFv-ETA'
      is efficacious against CML in vitro, providing the basis for a novel therapeutic
      strategy for the treatment of CML patients. 

PMID- 23954810
TI  - Insight into lymphoid tissue morphogenesis.
AB  - Secondary lymphoid organs (SLO) are crucial structures for immune-surveillance
      and rapid immune responses allowing resident lymphocytes to encounter antigen
      presenting cells that carry antigens from peripheral tissues. These structures
      develop during embryonic life through a tightly regulated process that involves
      interactions between haematopoietic and mesenchymal cells. Importantly, this
      morphogenesis potential is maintained throughout life since in chronic
      inflammatory conditions novel "tertiary lymphoid organs" can be generated by
      processes that are reminiscent of embryonic SLO development. In this review we
      will discuss early events in SLO morphogenesis, focusing on haematopoietic and
      mesenchymal cell subsets implicated on the development of lymphoid organs.

PMID- 23954812
TI  - Perceptual consequence of normalization revealed by a novel brightness induction.
AB  - The human brain is renowned for its dynamic regulation of sensory inputs, which
      enables our brain to operate under an enormous range of physical energy with
      sensory neurons whose processing range is limited. Here we present a novel and
      strong brightness induction that reflects neural mechanisms underlying this
      dynamic regulation of sensory inputs. When physically identical, stationary and
      moving objects are viewed simultaneously, the stationary and moving objects
      appear largely different. Experiments reveal that normalization at multiple
      stages of visual processing provides a plausible account for the large shifts in
      perceptual experiences, observed in both the stationary and the moving objects.
      This novel brightness induction suggests that brightness of an object is
      influenced not only by variations in surrounding light (i.e. simultaneous
      contrast) but also by dynamically changing neural responses associated with
      stimulus motion. 

PMID- 23954811
TI  - Differences in CXCR7 protein expression on rat versus mouse and human splenic
      marginal zone B cells.

PMID- 23954813
TI  - Predictability of spatial and non-spatial target properties improves perception
      in the pre-saccadic interval.
AB  - In a dual-task paradigm with a perceptual discrimination task and a concurrent
      saccade task, we examined participants' ability to make use of prior knowledge of
      a critical property of the perceptual target to improve discrimination. Previous
      research suggests that during a short time window before a saccade, covert
      attention is imperatively directed towards the saccade target location.
      Consequently, discrimination of perceptual targets at the saccade target location
      is better than at other locations. We asked whether the obligatory pre-saccadic
      attention shift prevents perceptual benefits arising for perceptual target
      stimuli with predictable as opposed to non-predictable properties. We compared
      conditions in which the color or location of the perceptual target was constant
      to conditions in which those properties varied randomly across trials. In
      addition to the expected improvements of perception at the saccade target
      location, we found perception to be better with constant than with random
      properties of the perceptual target. Thus, color or location information about an
      upcoming perceptual target facilitates perception even while spatial attention is
      shifted to the saccade target. The improvement occurred irrespective of the
      saccade target location, which suggests that the underlying mechanism is
      independent of the pre-saccadic attention shift, but alternative interpretations
      are discussed as well. 

PMID- 23954814
TI  - Cryopreservation of rat MSCs by use of a programmed freezer with magnetic field.
AB  - Mesenchymal stem cells (MSCs) can be used for the regeneration of various tissues
      and cryopreservation of MSCs is so important for regenerative medicine. The
      purpose of this study was to evaluate the influences of cryopreservation on MSCs
      by use of a programmed freezer with a magnetic field (CAS freezer). MSCs were
      isolated from bone marrow of rat femora. The cells were frozen by a CAS freezer
      with 10% dimethyl sulfoxide (Me2SO) and cryopreserved for 7 days at a temperature
      of -150  degrees C. Immediately after thawing, the number of survived cells was
      counted. The cell proliferation also examined after 48 h culture. Next, MSCs were
      frozen by two different freezers; CAS freezer and a conventional programmed
      freezer without magnetic field. Then, osteogenic and adipogenic differentiations
      of cryopreserved cells were examined. As a result, survival and proliferation
      rates of MSCs were significantly higher in CAS freezer than in the non-magnetic
      freezer. Alizarin positive reaction, large amount of calcium quantification, and
      greater alkaline phosphatase activity were shown in both the non-cryopreserved
      and CAS groups after osteogenic differentiation. Moreover, Oil Red O staining
      positive reaction and high amount of PPARgamma and FABP4 mRNAs were shown in both
      the non-cryopreserved and CAS groups after adipogenic differentiation. From these
      findings, it is shown that a CAS freezer can maintain high survival and
      proliferation rates of MSCs and maintain both adipogenic and osteogenic
      differentiation abilities. It is thus concluded that CAS freezer is available for
      cryopreservation of MSCs, which can be applied to various tissue regeneration.

PMID- 23954815
TI  - Pilot-scale investigation of the robustness and efficiency of a copper-based
      treated wood wastes recycling process.
AB  - The disposal of metal-bearing treated wood wastes is becoming an environmental
      challenge. An efficient recycling process based on sulfuric acid leaching has
      been developed to remove metals from copper-based treated wood chips (0<x<12 mm).
      The present study explored the performance and the robustness of this technology
      in removing metals from copper-based treated wood wastes at a pilot plant scale
      (130-L reactor tank). After 3 * 2 h leaching steps followed by 3 * 7 min rinsing
      steps, up to 97.5% of As, 87.9% of Cr, and 96.1% of Cu were removed from CCA
      treated wood wastes with different initial metal loading (>7.3 kgm(-3)) and more
      than 94.5% of Cu was removed from ACQ-, CA- and MCQ-treated wood. The treatment
      of effluents by precipitation-coagulation was highly efficient; allowing removals
      more than 93% for the As, Cr, and Cu contained in the effluent. The economic
      analysis included operating costs, indirect costs and revenues related to
      remediated wood sales. The economic analysis concluded that CCA-treated wood
      wastes remediation can lead to a benefit of 53.7 US$t(-1) or a cost of 35.5 US$t(
      1) and that ACQ-, CA- and MCQ-treated wood wastes recycling led to benefits
      ranging from 9.3 to 21.2 US$t(-1).

PMID- 23954816
TI  - Miconazole-loaded nanostructured lipid carriers (NLC) for local delivery to the
      oral mucosa: improving antifungal activity.
AB  - Miconazole is a widely used antifungal agent with poor aqueous solubility, which
      requires the development of drug delivery systems able to improve its therapeutic
      activity. For this purpose, a miconazole-loaded nanostructured lipid carriers
      (NLC) dispersion was prepared and characterized. Further, the dispersion was used
      to prepare a NLC-based hydrogel formulation proposed as an alternative system to
      improve the local delivery of miconazole to the oral mucosa. NLC dispersion
      showed particles in the nanometer range (~ 200 nm) with low polidispersity index
      (<0.3), good physical stability and high encapsulation efficiency (>87%). A
      controlled miconazole release was observed from NLC and NLC-based hydrogel
      formulations, in contrast to a commercial oral gel formulation, which
      demonstrated a faster release. Additionally, it was observed that the
      encapsulation of miconazole in the NLC improved its antifungal activity against
      Candida albicans. Therefore, it was demonstrated that the encapsulation of
      miconazole in NLC allows for obtaining the same therapeutic effect of a
      commercial oral gel formulation, using a 17-fold lower dose of miconazole.

PMID- 23954818
TI  - Qualitative changes in the proteome of extracellular vesicles accompanying cancer
      cell transition to mesenchymal state.
AB  - Transitions of the cancer cell phenotype between epithelial and mesenchymal
      states (EMT) are likely to alter the patterns of intercellular communication. In
      this regard we have previously documented that EMT-like changes trigger
      quantitative rearrangements in exosomal vesicle emission in A431 cancer cells
      driven by oncogenic epidermal growth factor receptor (EGFR). Here we report that
      extracellular vesicles (EVs) produced by these cancer cells in their epithelial
      and mesenchymal states exhibit profound qualitative differences in their
      proteome. Thus, induction of the EMT-like state through blockade of E-cadherin
      and EGFR stimulation provoked a mesenchymal shift in cellular morphology and
      enrichment in the CD44-high/CD24-low immunophenotype, often linked to cellular
      stemness. This change also resulted in reprogramming of the EV-related proteome
      (distinct from that of corresponding cells), which contained 30 unique protein
      signals, and revealed enrichment in pathways related to cellular growth, cell-to
      cell signaling, and cell movement. Some of the most prominent EV-related proteins
      were validated, including integrin alpha2 and tetraspanin CD9. We propose that
      changes in cellular differentiation status translate into unique qualitative
      rearrangements in the cargo of EVs, a process that may have implications for
      intercellular communication and could serve as source of new biomarkers to detect
      EMT-like processes in cancer.

PMID- 23954819
TI  - Activin A and Wnt-dependent specification of human definitive endoderm cells.
AB  - Activin/Nodal and Wnt signaling are known to play important roles in the regional
      specification of endoderm. Here we have investigated the effect of the length of
      stimulation with Activin A plus Wnt3a on the development of hepatic and
      pancreatic progenitors from the definitive endoderm (DE) cells derived from human
      pluripotent stem cells (hPSC). We show that DE-cells derived from hPSC with 3
      days high Activin A and Wnt3a treatment were able to differentiate further into
      both tested endodermal lineages. When prolonging the DE-induction protocol from 3
      to 5 or 7 days, almost pure DE-marker positive cell populations were obtained.
      However, these cells had an impaired pancreatic differentiation capacity, while
      they still developed into hepatocyte-like cells. Further propagation of the DE
      cells in the presence of Wnt3a and Activin A led to the complete loss of
      differentiation capacity into hepatic or pancreatic lineages. When Wnt3a was
      removed after 24h from the initiation of the differentiation, the cells were able
      to differentiate into PDX1+/NKX6.1+ pancreatic progenitors even with longer DE
      induction time while efficiency of hepatic differentiation was lower. Our results
      suggest that both the length and the timing of Wnt3a treatment during DE
      induction are crucial for the final differentiation outcome. Although it is
      possible to derive apparently pure DE cells with prolonged Activin A/Wnt
      stimulation, their progenitor capacity is restricted to a limited time window.

PMID- 23954817
TI  - Clathrin-independent endocytosis: a cargo-centric view.
AB  - Clathrin-independent endocytosis occurs in all cells and interest in this mode of
      cellular entry has grown. Although this form of endocytosis was first described
      for entry of bacterial toxins, here we focus our attention on the endogenous cell
      surface "cargo" proteins that enter cells by this mechanism. The cargo proteins
      entering by this mechanism are varied and include nutrient transporters, ion
      channels, cell adhesion molecules and proteins associated with the immune system.
      Despite the apparent lack of selection at the cell surface, we provide some
      examples of specific sorting of these cargo proteins after entry, leading to
      distinct itineraries and cellular fates. 

PMID- 23954820
TI  - The reversal of paraquat-induced mitochondria-mediated apoptosis by cycloartenyl
      ferulate, the important role of Nrf2 pathway.
AB  - In this study, we demonstrate the protective effects of Cycloartenyl ferulate
      (CF) against Paraquat (PQ)-induced cytotoxicity and elucidate the underlying
      molecular mechanisms. The results show that, CF could reverse the PQ-induced
      growth inhibition and release of lactate dehydrogenase in HK-2 human proximal
      tubular cells. Treatment with PQ induced apoptosis in HK-2 cells, as evidenced by
      accumulation of sub-G1 cell population, chromatin condensation, DNA
      fragmentation, and translocation of phosphatidylserine, which were significantly
      attenuated by co-incubation with CF. Mitochondria-mediated apoptosis pathway
      contributed importantly to PQ-induced apoptosis, as revealed by the activation of
      caspase-3/-9, cleavage of PARP, depletion of mitochondrial membrane potential
      regulated by Bcl-2 family members, and overproduction of reactive oxygen species,
      which were also effectively blocked by CF. Moreover, treatments of PQ strongly
      inhibited the expression of Nrf2 and the downstream effectors, HO1 and NQO1.
      However, co-treatment with CF effectively reversed this action of PQ.
      Furthermore, silencing of Nrf2 by the siRNA technique significantly blocked the
      cytoprotective effects of CF against PQ-induced apoptosis, which suggest the
      important role of Nrf2 signaling pathway an cell apoptosis induced by PQ. Taken
      together, this study provides a novel strategy for molecular intervention against
      PQ-induced nephrotoxicity by using phytochemicals. 

PMID- 23954821
TI  - Mitochondrial-related gene expression profiles suggest an important role of PGC
      1alpha in the compensatory mechanism of endemic dilated cardiomyopathy.
AB  - Keshan disease (KD) is an endemic dilated cardiomyopathy with unclear etiology.
      In this study, we compared mitochondrial-related gene expression profiles of
      peripheral blood mononuclear cells (PBMCs) derived from 16 KD patients and 16
      normal controls in KD areas. Total RNA was isolated, amplified, labeled and
      hybridized to Agilent human 4 * 44k whole genome microarrays. Mitochondrial
      related genes were screened out by the Third-Generation Human Mitochondria
      Focused cDNA Microarray (hMitChip3). Quantitative real-time PCR,
      immunohistochemical and biochemical parameters related mitochondrial metabolism
      were conducted to validate our microarray results. In KD samples, 34 up-regulated
      genes (ratios >= 2.0) were detected by significance analysis of microarrays and
      ingenuity systems pathway analysis (IPA). The highest ranked molecular and
      cellular functions of the differentially regulated genes were closely related to
      amino acid metabolism, free radical scavenging, carbohydrate metabolism, and
      energy production. Using IPA, 40 significant pathways and four significant
      networks, involved mainly in apoptosis, mitochondrion dysfunction, and nuclear
      receptor signaling were identified. Based on our results, we suggest that PGC
      1alpha regulated energy metabolism and anti-apoptosis might play an important
      role in the compensatory mechanism of KD. Our results may lead to the
      identification of potential diagnostic biomarkers for KD in PBMCs, and may help
      to understand the pathogenesis of KD.

PMID- 23954822
TI  - When sounds look right and images sound correct: cross-modal coherence enhances
      claims of pattern presence.
AB  - How do people decide whether a stimulus contains a pattern? One possibility is
      that they rely on a global, non-specific signal of coherence. Interestingly, this
      signal might reflect a combination of different stimulus sources. Consequently,
      the coherence of one stimulus might influence decisions about coherence of a
      second, unrelated stimulus. We explored this possibility in three experiments in
      which participants judged the presence of a pattern in targets from one sensory
      modality, while being exposed in the background to incidental coherent and
      incoherent stimuli in a different modality (visual->auditory, auditory->visual).
      Across all three experiments, using a variety of judgments, coherence of
      incidental background cross-modal patterns enhanced claims of pattern presence.
      These findings advance our understanding of how people judge order in the
      structured as well as in the unstructured world. 

PMID- 23954823
TI  - The test of truth: an experimental investigation of the norm of assertion.
AB  - Assertion is fundamental to our lives as social and cognitive beings.
      Philosophers have recently built an impressive case that the norm of assertion is
      factive. That is, you should make an assertion only if it is true. Thus far the
      case for a factive norm of assertion been based on observational data. This paper
      adds experimental evidence in favor of a factive norm from six studies. In these
      studies, an assertion's truth value dramatically affects whether people think it
      should be made. Whereas nearly everyone agreed that a true assertion supported by
      good evidence should be made, most people judged that a false assertion supported
      by good evidence should not be made. The studies also suggest that people are
      consciously aware of criteria that guide their evaluation of assertions. Evidence
      is also presented that some intuitive support for a non-factive norm of assertion
      comes from a surprising tendency people have to misdescribe cases of blameless
      rule-breaking as cases where no rule is broken. 

PMID- 23954824
TI  - Functional expression of P2 receptors in the inner ear of chicken embryo.
AB  - The purpose of the present study was to investigate the modulation of spontaneous
      afferent activity by ATP during embryonic development in a preparation isolated
      chicken inner ear. This work was performed using multiunit and single-unit
      extracellular recordings from the posterior semicircular canal nerve and the
      basilar papilla nerve. alpha,beta-meATP, a P2X receptor agonist, notably
      increased the discharge frequency of the vestibular afferents between E15 and
      E18, but not in the basilar papilla. In contrast, the P2Y receptor agonist UTP
      produced a slight increase in the discharge frequency of basilar papilla
      afferents, without apparent changes in the vestibular afferent activity. 2
      MeSATP, a P2Y agonist, increased the basal discharge of the primary afferents in
      a dose-age dependent way, but when we applied the antagonist of P2Y receptor,
      Reactive Blue 2 (10(-4)M), the effect of 2-MeSATP decreased significantly. This
      was observed both in vestibule and basilar papilla. Using RT-PCR the presence of
      P2X3, P2Y1, P2Y2 and P2Y6 mRNA was documented in the vestibular system with more
      important presence during the early stage (E15) than the later stage (E21),
      however in the basilar papilla we found only the P2Y1, P2Y2 and P2Y6 mRNA with
      the same temporal course as in the vestibule. These results confirm our
      pharmacological findings. Together this data suggests a role for P2X receptors
      mediated purinergic signaling in vestibular synaptic organization. Temporal
      changes in P2Y receptors during development might be involved in the
      establishment of the endolymphatic ion composition needed for normal vestibular
      and auditory transduction and/or specific cellular differentiation.

PMID- 23954825
TI  - Nuclear PKG localization is regulated by G0 alpha and is necessary in the AWB
      neurons to mediate avoidance in Caenorhabditis elegans.
AB  - Neural circuits interpret sensory information from their environment and use this
      information to influence behavioral outputs. In Caenorhabditis elegans two
      bilaterally symmetric cephalic amphid organs each contain the ciliated termini of
      twelve classes of sensory neurons. Two of these sensory neuron pairs are called
      the AWB and the AWC neurons. The AWC neurons confer an ability to detect
      attractive volatile odors such as benzaldehyde, whereas the AWB neurons endow the
      animal with an ability to detect repulsive volatile odors such as 2-nonanone.
      Previously, it has been shown that transient nuclear localization of a Protein
      Kinase G (PKG) called EGL-4 in the AWC neuron facilitates adaptation after
      sustained odor input, and here we show that constitutively nuclear EGL-4 is
      required in the AWB neurons for the detection of repellent odors. Furthermore, we
      show that the G0 alpha subunit protein GOA-1 regulates the nuclear localization
      of EGL-4 in both AWB and AWC neurons. These data reveal novel insight into how
      the localization of an individual kinase can form a turnout switch to modify
      output in different neurons to drive opposite sensory behaviors.

PMID- 23954826
TI  - Depletion of intracellular zinc induces apoptosis of cultured hippocampal neurons
      through suppression of ERK signaling pathway and activation of caspase-3.
AB  - Although Zinc depletion induces apoptosis in different cells and tissues, exact
      mechanism of this action of zinc depletion is not completely understood. In our
      previous study, the results suggested that the significant down-regulation of
      MEK/ERK signaling pathway was observed in zinc deficiency neurons. Here, we
      investigate whether, in hippocampal neurons, this increased rate of apoptosis
      induced by zinc depletion is the result of hypophosphorylation of ERK pathway. In
      this study, we found that NGF, ERK agonist, prevented neurons against TPEN
      induced apoptosis, whereas TPEN-induced apoptosis was potentiated by U0126,
      inhibitors of ERK. Moreover, TPEN-induced caspase-3 activity was further
      increased by the pretreatment with U0126, but it was further decreased by the
      pretreatment with NGF. However, pretreatment of the cells with U0126 or NGF had
      no effect on the changes of Bcl-2 and Bax protein expression induced by zinc
      depletion. Thus, the results indicate that TPEN induces apoptosis of hippocampal
      neurons through inhibition of ERK and, in turn, activation of caspase-3. 

PMID- 23954827
TI  - Wnt signaling pathways participate in Astragalus injection-induced
      differentiation of bone marrow mesenchymal stem cells.
AB  - Bone marrow mesenchymal stem cells (MSCs) have the capacity for self-renewal and
      multi-directional differentiation, and MSCs can differentiate into neuron-like
      cells under certain conditions. In this study, we used the traditional Chinese
      medicine Astragalus as an inducer. After 7 days of induction, the expression of
      specific markers was detected in each induced group by immunocytochemical
      staining. The results of real-time quantitative PCR and Western blot confirmed
      the immunocytochemistry analysis. We also tested some key genes and proteins of
      the Wnt signaling pathway, and found that they were increased in Astragalus
      treated groups. After treatment with lithium chloride (LiCl), the protein
      expression of phospho GSK-3beta and beta-catenin was increased in each group
      compared to the corresponding group without LiCl. These findings demonstrate that
      Astragalus injection can induce differentiation of MSCs into neuron-like cells
      and suggest that the process of differentiation might be mediated by activation
      of Wnt signaling pathways. 

PMID- 23954828
TI  - Dok5 is involved in the signaling pathway of neurotrophin-3 against TrkC-induced
      apoptosis.
AB  - TrkC is a dependence receptor and many reports have shown that neurotrophin-3
      promotes cell survival by inhibiting TrkC-induced apoptosis in many cell lines.
      However, the identity of the adaptor protein involved in the NT-3/TrkC signaling
      pathway regulating cell death and survival remains unclear. The downstream of
      tyrosine kinase/docking protein (Dok) adaptor protein 5 is one substrate of the
      TrkC receptor. Because NT-3 and its receptor, TrkC, are strongly expressed by
      sensory neurons, we measured the expression of Dok5 and TrkC in the developing
      mouse spinal cord and dorsal root ganglia (DRG). We found that the number of
      cells positive for both Dok5 and TrkC decreases with DRG development.
      Immunoprecipitation and immunofluorescence staining showed that Dok5 interacted
      with TrkC and partially colocalized with TrkC in DRG neurons. In HEK293T cells,
      TrkC triggered apoptosis, but NT-3 prevented TrkC-induced apoptosis.
      Interestingly, siRNA knockdown of Dok5 expression partially prevented the
      protection of NT-3 against TrkC-induced apoptosis by regulating the activity of
      caspase-3. Taken together, we concluded that Dok5 is necessary for NT-3 signaling
      to block TrkC-induced apoptosis. 

PMID- 23954829
TI  - Progesterone treatment improves cognitive outcome following experimental
      traumatic brain injury in rats.
AB  - Progesterone (PROG) has recently been shown to have a neuroprotective effect and
      improve cognitive outcome in animal models of traumatic brain injury (TBI).
      However, the precise mechanisms remain unclear. This study was aimed to
      investigate the inhibitory effects of PROG on inflammation and apoptosis in the
      hippocampus after TBI and its influence on the cognitive outcome. In this study,
      the model of TBI was established by modified Feeney's weight-dropping method. The
      PROG was given in a dose of 16 mg/kg by intraperitoneal injection 1h post injury
      and subsequent injections subcutaneously at 6h and 12 h after TBI. Brain samples
      were extracted at 24 h after trauma. The expression of COX-2 and caspase-3 was
      measured by immunohistochemistry and western blot technique. The cognitive
      outcome was assessed by Morris water maze test (MWM). The results revealed that
      the expression of COX-2 and caspase-3 in TBI-PROG group was distinctly less than
      those of the TBI group (p < 0.05). In addition, the performance of Morris water
      maze showed that progesterone treatment exhibited shorter latencies, more
      platform crossings and more time swimming in the quadrant area in the TBI+PROG
      rats compared to the TBI rats. In conclusion, post-TBI PROG administration may
      attenuate inflammation and apoptosis in the hippocampus, and this may be one of
      the mechanisms by which PROG improves cognitive outcome following TBI.

PMID- 23954830
TI  - Imitation and local enhancement: detrimental effects of consensus definitions on
      analyses of social learning in animals.
AB  - Development of a widely accepted vocabulary referring to various types of social
      learning has made important contributions to decades of progress in analyzing the
      role of socially acquired information in the development of behavioral
      repertoires. It is argued here that emergence of a consensus vocabulary, while
      facilitating both communication and research, has also unnecessarily restricted
      research on social learning. The article has two parts. In the first, I propose
      that Thorndike's (1898, 1911) definition of imitation as "learning to do an act
      from seeing it done" has unduly restricted studies of the behavioral processes
      involved in the propagation of behavior. In part 2, I consider the possibility
      that success in labeling social learning processes believed to be less
      cognitively demanding than imitation (e.g. local and stimulus enhancement, social
      facilitation, etc.) has been mistaken for understanding of those processes,
      although essentially nothing is known of their stimulus control, development,
      phylogeny or substrate either behavioral or physiological. 

PMID- 23954831
TI  - Vocalizations associated with pectoral fin contact in bottlenose dolphins
      (Tursiops truncatus).
AB  - Pectoral fin contact in bottlenose dolphins represents one form of tactile
      communication. Acoustic communication associated with pectoral fin contact is an
      additional level of communication that may change or enhance the tactile message
      between two individuals. In this study, we examine vocalization types associated
      with pectoral fin contact in a group of captive bottlenose dolphins (Tursiops
      truncatus). From 2006 to 2009, vocalizations potentially associated with 748
      pectoral fin contacts were examined: whistles, click trains and overlap of
      whistles and click trains were documented when associated with fin contact.
      Dolphins were also documented not vocalizing when exchanging pectoral fin
      contacts. Call type associated with pectoral fin contact was compared for the
      proportion of the type of pectoral fin contact, vocalizer sex, initiator and
      receiver roles, and gender pair. Overall, vocalizations differed significantly by
      vocalizer role as rubber or rubbee, initiator, and sex. Receivers and rubbees
      clicked and used overlap vocalizations more frequently, and males produced
      overlap vocalizations more frequently. These results suggest that whistles may be
      used to initiate pectoral fin contact or show preference for a particular
      partner, while click trains may be used to show disinterest in pectoral fin
      contact or to signal the end of a contact. Examining vocalizations produced in
      conjunction with tactile contact is a relatively new approach in the study of
      individual dolphin behavior and may be useful for understanding dolphin social
      alliances and social preferences for various individuals within a population. 

PMID- 23954832
TI  - Response elimination, reinforcement rate and resurgence of operant behavior.
AB  - The effects of reinforcement rate of alternative responding on resurgence were
      studied in six experiments with pigeons. In Experiment 1A, key pecking was
      maintained on a multiple variable-interval (VI) VI schedule in the Training
      phase. In the Response-Elimination phase, a variable differential-reinforcement
      of-other-behavior (DRO) schedule was in effect in each component. Reinforcement
      rates were equal and then, higher in one (rich) component, and lower in the other
      (lean), than in the Training phase. More resurgence occurred in the lean
      component, but this could have resulted from response-rate differences between
      components in the Training-phase. Experiment 1B was a replication of Experiment
      1A, but with experimentally-naive pigeons. Response-Elimination phase
      reinforcement rates were manipulated systematically in subsequent experiments: In
      Experiment 2, reinforcement rate was equal, in one component, and lower or higher
      in the other, than in the Training phase. In Experiment 3, reinforcers were
      discontinued before differential reinforcement rates were effected. In Experiment
      4, reinforcement rates first were differential and, then, equal to those in the
      Training phase. In Experiments 5 and 6, differential reinforcement rates were
      arranged by using fixed-DROs and VIs for pecking a different key, respectively.
      Even though resurgence was not obtained with every pigeon, at least some small
      magnitude resurgence occurred in each experiment and was not related
      systematically to reinforcement rates of alternative responding. Schedule
      differences, response topography, order of conditions and the length of each
      phase were not sufficient to account for these results. 

PMID- 23954834
TI  - Circadian regulation of hemolymph and ovarian ecdysteroids during egg development
      in the insect Rhodnius prolixus (Hemiptera).
AB  - Ecdysteroids, classically studied as the molting hormones of insects, occur at
      lower levels in the adult stage, but their source and significance in adult
      physiology is debated. In Rhodnius prolixus, a blood meal initiates a cycle of
      egg development and ecdysteroids appeared in the hemolymph within 1-2h of
      feeding. Systematic changes in hemolymph ecdysteroid titer then occurred during
      egg development. There was a clear circadian rhythm in the hemolymph ecdysteroid
      titer throughout egg development. This is the first report of an ecdysteroid
      rhythm in any adult female insect. Of various tissues examined in vitro, only
      ovaries released ecdysteroids. The amounts released were adequate to account for
      observed hemolymph ecdysteroid titers. Therefore, ovaries are the primary,
      perhaps sole, source of hemolymph ecdysteroids. Ovaries in vitro showed a
      circadian rhythm of changes in ecdysteroid content and release that was in
      synchrony with the hemolymph ecdysteroid rhythm, indicating that ovarian
      ecdysteroid release drives the rhythm seen in the hemolymph. Potential regulation
      of ovarian ecdysteroids is discussed in relation to the known rhythms in
      prothoracicotropic hormone and insulin-like peptides that occur during egg
      development. The prospect of circadian regulation of egg development itself by
      hormones and/or an ovarian clock is also discussed. 

PMID- 23954833
TI  - Statistical equivalence and test-retest reliability of delay and probability
      discounting using real and hypothetical rewards.
AB  - Delay discounting (DD) and probability discounting (PD) refer to the reduction in
      the subjective value of outcomes as a function of delay and uncertainty,
      respectively. Elevated measures of discounting are associated with a variety of
      maladaptive behaviors, and confidence in the validity of these measures is
      imperative. The present research examined (1) the statistical equivalence of
      discounting measures when rewards were hypothetical or real, and (2) their 1-week
      reliability. While previous research has partially explored these issues using
      the low threshold of nonsignificant difference, the present study fully addressed
      this issue using the more-compelling threshold of statistical equivalence. DD and
      PD measures were collected from 28 healthy adults using real and hypothetical $50
      rewards during each of two experimental sessions, one week apart. Analyses using
      area-under-the-curve measures revealed a general pattern of statistical
      equivalence, indicating equivalence of real/hypothetical conditions as well as 1
      week reliability. Exceptions are identified and discussed. 

PMID- 23954835
TI  - The heat shock protein (Hsp) 70 of Cryptococcus neoformans is associated with the
      fungal cell surface and influences the interaction between yeast and host cells.
AB  - The pathogenic yeast Cryptococcus neoformans secretes numerous proteins, such as
      heat shock proteins, by unconventional mechanisms during its interaction with
      host cells. Hsp70 is a conserved chaperone that plays important roles in various
      cellular processes, including the interaction of fungi with host immune cells.
      Here, we report that sera from individuals with cryptococcosis infection
      recognize a recombinant C. neoformans Hsp70 (Cn_rHsp70). Moreover,
      immunofluorescence assays using antibodies against Cn_rHsp70 revealed the
      localization of this protein at the cell surface mainly in association with the
      capsular network. We found that the addition of Cn_rHsp70 positively modulated
      the interaction of C. neoformans with human alveolar epithelial cells and
      decreased fungal killing by mouse macrophages, without affecting phagocytosis
      rates. Immunofluorescence analysis showed that there was a competitive
      association among the receptor, GXM and Cn_rHsp70, indicating that the Hsp70
      binding sites in host cells appear to be shared by glucuronoxylomannan (GXM), the
      major capsular antigen in C. neoformans. Our observations suggest additional
      mechanisms by which Hsp70 influences the interaction of C. neoformans with host
      cells. 

PMID- 23954836
TI  - Reference intervals of D-dimer during the pregnancy and puerperium period on the
      STA-R evolution coagulation analyzer.
AB  - BACKGROUND: Pregnant women are at a hyper-coagulable state with a higher risk of
      deep venous thromboembolism (VTE) and disseminated intravascular coagulation
      (DIC), which could be life threatening. We established gestational age-specific
      reference intervals for D-dimer, and estimate the role of D-dimer test in ruling
      out VTE and DIC in pregnant women. METHODS: We followed 1343 healthy pregnant
      women and 1042 uncomplicated postpartum women to establish gestational age
      specific reference intervals of D-dimer during normal pregnancy. Eighty
      uncomplicated non-pregnant women were chosen as control group. D-dimer testing
      was also performed among the patients with pregnancy-related complications.
      RESULTS: D-dimer concentration increased progressively during the pregnancy and
      peaked at the first postpartum day, and then it began to decrease steadily and
      reach to non-pregnant concentrations on the 42nd postpartum day. The results of
      several cases that had clinical suspicion of VTE were compared with those of the
      reference group. CONCLUSIONS: The study provides reference intervals of D-dimer
      during the pregnancy and postpartum period for women of Chinese Han ethnicity
      using latex-based immunoturbidimetry on the STA-R evolution coagulation analyzer.
      Further studies are needed to validate these reference ranges and assess the
      clinical utility of the reference intervals for D-dimer.

PMID- 23954837
TI  - Association of alkaline phosphatase with acute myocardial infarction in a
      population with high prevalence of hypovitaminosis D.
AB  - BACKGROUND: Since Pakistanis have high prevalence of hypovitaminosis-D as well as
      acute myocardial infarction (AMI), the objective of the study was to investigate
      the relationship between vitamin-D deficiency and risk of AMI in a hospital-based
      population and to identify major risk factors for this disease. METHODS: Fasting
      serum samples from 66 consecutive AMI patients [age 30-70 y] and 132 gender and
      age-matched (within 5 y) healthy controls were analyzed for concentrations of
      glucose, total-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides,
      calcium, inorganic phosphate, alkaline phosphatase (ALP), bone-ALP, parathyroid
      hormone (PTH), 25(OH) vitamin-D (25(OH)D) and alanine aminotransferase. RESULTS:
      Mean concentrations of serum 25(OH)D, PTH, total-ALP, bone-ALP, LDL-cholesterol,
      HDL-cholesterol and glucose were significantly different compared to healthy
      controls (p<0.05). Percent vitamin-D deficiency/insufficiency (levels<30 ng/ml)
      was significantly greater in AMI patients compared to controls (93.9% vs.75.8%;
      p=0.001). Multiple conditional logistic regression analysis revealed that
      increased levels of 25(OH)D were associated with decreased risk of AMI [MAOR (95%
      CI)=0.821 (0.718, 0.940); p=0.004]. Hypertension and smoking were positively
      associated with AMI. CONCLUSIONS: Increased vitamin-D levels were associated with
      decreased risk of AMI, while serum glucose, bone-ALP, hypertension and smoking
      were positively associated with it. Association of bone-ALP with AMI in
      hypovitaminosis-D is a novel finding of this study.

PMID- 23954838
TI  - Development of a saliva collection device for use in the field.
AB  - BACKGROUND: For monitoring biomarkers, saliva has several distinct advantages
      over other biological fluids. Saliva sampling is relatively non-invasive and
      enables the collection from either adults or infants under many different
      circumstances. However, there is no collection device that can be speedily used
      for analysis in the field. The aim of the present study was to evaluate the
      suitability of a new device, termed Muddler, compared with commercially available
      collection devices. METHODS: Saliva was collected from healthy volunteers. The
      collection devices such as Muddler, eye sponge, Salivette(r) Cotton (SC) and
      Salivette(r) Synthetic (SS) were evaluated in terms of the volume and/or
      composition of the collected saliva. The amounts of immunoglobulin A (IgA) and
      lactofferin in saliva were assessed by the enzyme-linked immunosorbent assays
      with the corresponding antibodies. Amylase activity was measured using a
      commercially available kit, and high molecular weight complexes including mucin
      were assessed by SDS-PAGE staining. RESULTS: A newly developed Muddler, which was
      made of plastic plate, was the best device for collecting a constant volume of
      saliva among all the devices examined in the present study. Furthermore, Muddler
      can collect without change in composition of salivary proteins such as IgA,
      lactoferrin, amylase, and mucin complex, whereas the levels of the salivary
      proteins obtained with all the commercial devices used were clearly different
      from those in original saliva. CONCLUSIONS: The newly developed Muddler was the
      best collection device in terms of the accuracy of collection and the reliability
      of measurements among all the devices examined in the present study.

PMID- 23954839
TI  - Red blood cell distribution width is a potential index to assess the disease
      activity of systemic lupus erythematosus.
AB  - BACKGROUND: General population-based investigations have revealed that red blood
      cell distribution width (RDW) is associated with inflammatory indexes such as
      erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Chronic
      inflammation is one of the major components of many autoimmune diseases and RDW
      may reflect the severity of these autoimmune diseases as well. Therefore, the
      objective of this study was to investigate the correlation between RDW and
      disease activity of systemic lupus erythematosus (SLE). METHODS: The medical
      records of 131 SLE patients were retrospectively analyzed. Correlations between
      RDW and disease activity or other inflammatory indexes were analyzed. The effect
      of glucocorticoid treatment for three months on RDW was estimated in 3 newly
      diagnosed SLE cases. RESULTS: Increased RDW was observed in SLE patients. RDW was
      positively correlated with serum IgM, CRP, ESR, and SLE Disease Activity Index
      2000 (SLEDAI-2K). Glucocorticoid treatment decreased both SLEDAI-2K and RDW.
      CONCLUSION: RDW may be a useful index to estimate the disease activity of SLE.

PMID- 23954840
TI  - Temporal behavior of capsule enlargement by Cryptococcus neoformans.
AB  - Microbial capsules are important virulence traits that mediate cell-host
      interactions and provide protection against host immune defense mechanisms.
      Cryptococcus neoformans is a yeast-like fungus that is capable of synthesizing a
      complex polysaccharide (PS) capsule that is required for causing disease.
      Microscopic visualization of capsule enlargement is difficult, because the
      capsule is a highly hydrated structure with an index of refraction that is very
      close to that of aqueous medium. In this study, we took advantage of the capsular
      reaction ("quellung" effect) produced by IgM monoclonal antibody (MAb) 13F1 to
      increase the refraction index difference between capsule and medium such that we
      visualized the capsule using differential interference contrast (DIC) microscopy.
      Time-lapse size measurements allowed us to quantify the growth rate of the
      capsule relative to that of the cell body. The increase in capsule volume per
      unit of time was consistent with a logistic variable slope model in which the
      capsule's final size was proportional to the rate of its growth. The rate of
      capsule growth (0.3 to 2.5 um(3)/min) was at least 4-fold faster than the rate of
      cell body growth (0.1 to 0.3 um(3)/min), and there was large cell-to-cell
      variation in the temporal kinetics of capsule and cellular growth. Previous to
      the first cellular replication event, both the capsule and cell body enlarged
      simultaneously, and their differences showed monotonic growth, which was affected
      only by its rate of volume increase per unit of time. Using these results, we
      provide an updated model for cryptococcal capsule biogenesis. 

PMID- 23954841
TI  - Impact of environmental conditions on the form and function of Candida albicans
      biofilms.
AB  - Candida albicans, like other pathogens, can form complex biofilms on a variety of
      substrates. However, as the number of studies of gene regulation, architecture,
      and pathogenic traits of C. albicans biofilms has increased, so have differences
      in results. This suggests that depending upon the conditions employed, biofilms
      may vary widely, thus hampering attempts at a uniform description. Gene
      expression studies suggest that this may be the case. To explore this hypothesis
      further, we compared the architectures and traits of biofilms formed in RPMI 1640
      and Spider media at 37 degrees C in air. Biofilms formed by a/alpha cells in the
      two media differed to various degrees in cellular architecture, matrix
      deposition, penetrability by leukocytes, fluconazole susceptibility, and the
      facilitation of mating. Similar comparisons of a/a cells in the two media,
      however, were made difficult given that in air, although a/a cells form
      traditional biofilms in RPMI medium, they form polylayers composed primarily of
      yeast cells in Spider medium. These polylayers lack an upper hyphal/matrix
      region, are readily penetrated by leukocytes, are highly fluconazole susceptible,
      and do not facilitate mating. If, however, air is replaced with 20% CO2, a/a
      cells make a biofilm in Spider medium similar architecturally to that of a/alpha
      cells, which facilitates mating. A second, more cursory comparison is made
      between the disparate cellular architectures of a/a biofilms formed in air in
      RPMI and Lee's media. The results demonstrate that C. albicans forms very
      different types of biofilms depending upon the composition of the medium, level
      of CO2 in the atmosphere, and configuration of the MTL locus. 

PMID- 23954842
TI  - Vero cells expressing porcine circovirus type 2-capsid protein and their
      diagnostic application.
AB  - Porcine circovirus type 2 (PCV2) is the causative agent of postweaning
      multisystemic wasting syndrome (PMWS) in swine. Although the incidences of PCV2
      related diseases are ubiquitous throughout the world, the serological tools are
      rather limited, mainly because the virus does not induce any cytopathic effects
      in cells. The purpose of this study was to develop a rapid, sensitive and easy
      quantitative immunofluorescence assay (QIFA) using the recombinant PCV2
      nucleocapsid protein (NCP) for the detection of PCV2-specific antibodies in pig
      sera. The recombinant PCV2 NCP was expressed in Vero cells by a lentivirus
      system. The performance of QIFA using these Vero cells as a diagnostic antigen
      was compared with currently available C-ELISA and I-ELISA; the relative
      sensitivity turned out to range from 92.5% up to 99.3%. The relative specificity
      was 93.3% when compared to C-ELISA as the gold standard. The serological
      experiment also indicated the inverse relationship between QIFA and the viral
      load in serum, semen, feces samples from 7 PCV2-positive boars. In addition, the
      PCV2 sequence detected from bone marrow cells shows 99% of sequence identity with
      PCV2 genome, confirming the infectivity of PCV2. 

PMID- 23954843
TI  - Evaluation of a simple and cost effective filter paper-based shipping and storage
      medium for environmental sampling of F-RNA coliphages.
AB  - Male specific RNA (F-RNA) coliphages are used as indicators of fecal
      contamination and for source tracking. However, collecting fecal samples for
      analysis from remote sites is problematic due to the need for an uninterrupted
      cold chain to guarantee sample suitability for downstream molecular detection of
      these coliphages. Here, we investigated the feasibility of using filter paper as
      a collection and storage vehicle for F-RNA coliphages. Various concentrations
      (10(1) to 10(4)pfu) of two F-RNA coliphages, MS2 and Qbeta, were prepared in
      lambda buffer or a 10% bovine manure slurry, spotted onto filter paper disks,
      dried, and maintained at 37  degrees C for up to 37 days. Nucleic acids were
      extracted from the spotted filter paper disks at 0, 6, 13, and 37 days post
      inoculation and analyzed by real time RT-PCR. F-RNA coliphages at concentrations
      of 10(2)pfu/filter paper unit were readily detected, and only a slight decrease
      in nucleic acid detection was observed over time. Furthermore, the sensitivity of
      real time RT-PCR detection of the F-RNA coliphage RNA was similar between the
      developed filter paper sampling methodology and traditional cold storage. These
      results indicate that filter paper is a suitable storage and transport medium for
      F-RNA coliphages when refrigeration is not possible.

PMID- 23954845
TI  - An overview of current and potential use of information and communication
      technologies for immunization promotion among adolescents.
AB  - Information and communication technologies (ICT), such as the Internet or mobile
      telephony, have become an important part of the life of today's adolescents and
      their main means of procuring information. The new generation of the Internet
      based on social-networking technologies, Web 2.0, is increasingly used for health
      purposes by both laypeople and health professionals. A broad spectrum of Web 2.0
      applications provides several opportunities for healthcare workers, in that they
      can reach large numbers of teenagers in an individualized way and promote vaccine
      related knowledge in an interactive and entertaining manner. These applications,
      namely social-networking and video-sharing websites, wikis and microblogs, should
      be monitored in order to identify current attitudes toward vaccination, to reply
      to vaccination critics and to establish a real-time dialog with users. Moreover,
      the ubiquity of mobile telephony makes it a valuable means of involving teenagers
      in immunization promotion, especially in developing countries. 

PMID- 23954844
TI  - All's well that transcribes well: non-coding RNAs and post-stroke brain damage.
AB  - The mammalian genome is replete with various classes of non-coding (nc) RNA
      genes. Many of them actively transcribe, and their relevance to CNS diseases is
      just beginning to be understood. CNS is one of the organs in the body that shows
      very high ncRNAs activity. Recent studies demonstrated that cerebral ischemia
      rapidly changes the expression profiles of different classes of ncRNAs: including
      microRNA, long noncoding RNA and piwi-interacting RNA. Several studies further
      showed that post-ischemic neuronal death and/or plasticity/regeneration can be
      altered by modulating specific microRNAs. These studies are of interest for
      therapeutic development as they may contribute to identifying new ncRNA targets
      that can be modulated to prevent secondary brain damage after stroke. 

PMID- 23954846
TI  - Elevation of dopamine induced by cigarette smoking: novel insights from a [11C]-+
      PHNO PET study in humans.
AB  - Positron emission tomography (PET) has convincingly provided in vivo evidence
      that psychoactive drugs increase dopamine (DA) levels in human brain, a feature
      thought critical to their reinforcing properties. Some controversy still exists
      concerning the role of DA in reinforcing smoking behavior and no study has
      explored whether smoking increases DA concentrations at the D3 receptor,
      speculated to have a role in nicotine's addictive potential. Here, we used PET
      and [(11)C]-(+)-PHNO ([(11)C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H
      naphtho[1,2-b][1,4]oxazin-9-ol) to test the hypothesis that smoking increases DA
      release (decreases [(11)C]-(+)-PHNO binding) in D2-rich striatum and D3-rich
      extra-striatal regions and is related to craving, withdrawal and smoking
      behavior. Ten participants underwent [(11)C]-(+)-PHNO scans after overnight
      abstinence and after smoking a cigarette. Motivation to smoke (smoking
      topography), mood, and craving were recorded. Smoking significantly decreased
      self-reported craving, withdrawal, and [(11)C]-(+)-PHNO binding in D2 and D3-rich
      areas (-12.0 and -15.3%, respectively). We found that motivation to smoke (puff
      rate) predicted magnitude of DA release in limbic striatum, and the latter was
      correlated with decreased craving and withdrawal symptoms. This is the first
      report suggesting that, in humans, DA release is increased in D3-rich areas in
      response to smoking. Results also support the preferential involvement of the
      limbic striatum in motivation to smoke, anticipation of pleasure from cigarettes
      and relief of withdrawal symptoms. We propose that due to the robust effect of
      smoking on [(11)C]-(+)-PHNO binding, this radiotracer represents an ideal
      translational tool to investigate novel therapeutic strategies targeting DA
      transmission. 

PMID- 23954847
TI  - Volatile solvents as drugs of abuse: focus on the cortico-mesolimbic circuitry.
AB  - Volatile solvents such as those found in fuels, paints, and thinners are found
      throughout the world and are used in a variety of industrial applications.
      However, these compounds are also often intentionally inhaled at high
      concentrations to produce intoxication. While solvent use has been recognized as
      a potential drug problem for many years, research on the sites and mechanisms of
      action of these compounds lags behind that of other drugs of abuse. In this
      review, we first discuss the epidemiology of voluntary solvent use throughout the
      world and then consider what is known about their basic pharmacology and how this
      may explain their use as drugs of abuse. We next present data from preclinical
      and clinical studies indicating that these substances induce common addiction
      sequelae such as dependence, withdrawal, and cognitive impairments. We describe
      how toluene, the most commonly studied psychoactive volatile solvent, alters
      synaptic transmission in key brain circuits such as the mesolimbic dopamine
      system and medial prefrontal cortex (mPFC) that are thought to underlie addiction
      pathology. Finally, we make the case that activity in mPFC circuits is a critical
      regulator of the mesolimbic dopamine system's ability to respond to volatile
      solvents like toluene. Overall, this review provides evidence that volatile
      solvents have high abuse liability because of their selective effects on critical
      nodes of the addiction neurocircuitry, and underscores the need for more research
      into how these compounds induce adaptations in neural circuits that underlie
      addiction pathology. 

PMID- 23954848
TI  - Antidepressant-like properties of novel HDAC6-selective inhibitors with improved
      brain bioavailability.
AB  - HDAC inhibitors have been reported to produce antidepressant and pro-cognitive
      effects in animal models, however, poor brain bioavailability or lack of isoform
      selectivity of current probes has limited our understanding of their mode of
      action. We report the characterization of novel pyrimidine hydroxyl amide small
      molecule inhibitors of HDAC6, brain bioavailable upon systemic administration. We
      show that two compounds in this family, ACY-738 and ACY-775, inhibit HDAC6 with
      low nanomolar potency and a selectivity of 60- to 1500-fold over class I HDACs.
      In contrast to tubastatin A, a reference HDAC6 inhibitor with similar potency and
      peripheral activity, but more limited brain bioavailability, ACY-738 and ACY-775
      induce dramatic increases in alpha-tubulin acetylation in brain and stimulate
      mouse exploratory behaviors in novel, but not familiar environments.
      Interestingly, despite a lack of detectable effect on histone acetylation, we
      show that ACY-738 and ACY-775 share the antidepressant-like properties of other
      HDAC inhibitors, such as SAHA and MS-275, in the tail suspension test and social
      defeat paradigm. These effects of ACY-738 and ACY-775 are directly attributable
      to the inhibition of HDAC6 expressed centrally, as they are fully abrogated in
      mice with a neural-specific loss of function of HDAC6. Furthermore, administered
      in combination, a behaviorally inactive dose of ACY-738 markedly potentiates the
      anti-immobility activity of a subactive dose of the selective serotonin reuptake
      inhibitor citalopram. Our results validate new isoform-selective probes for in
      vivo pharmacological studies of HDAC6 in the CNS and reinforce the viability of
      this HDAC isoform as a potential target for antidepressant development. 

PMID- 23954850
TI  - Cathepsin D levels are reduced in patients with preeclampsia in Korean
      population.
AB  - OBJECTIVES: To compare the circulating levels of cathepsin D in preeclamptic and
      normotensive pregnancies. DESIGN AND METHODS: Fifty pregnant and 20 healthy non
      pregnant patients were enrolled in this study. Of the 50 pregnant patients, 15
      were preeclamptic and 35 patients were normotensive. Serum levels of soluble
      cathepsin D were measured with an enzyme-linked immunosorbent assay (ELISA) kit.
      RESULTS: Cathepsin D levels were significantly lower in preeclamptic patients
      than normotensive pregnant patients (p=0.033). The serum levels of cathepsin D in
      preeclamptic and non-pregnant healthy patients showed similar results. The serum
      levels of cathepsin D were not positively correlated with preeclampsia severity
      or the incidence of delivery of small for gestational age infants. CONCLUSIONS:
      We conclude that a reduced cathepsin D level is an important factor that may
      contribute to the pathogenesis of preeclampsia, possibly by inhibiting normal
      trophoblastic invasion. These results contribute to the understanding of this
      serious obstetric problem.

PMID- 23954849
TI  - Intra-hippocampal transplantation of neural precursor cells with transgenic over
      expression of IL-1 receptor antagonist rescues memory and neurogenesis
      impairments in an Alzheimer's disease model.
AB  - Ample evidence implicates neuroinflammatory processes in the etiology and
      progression of Alzheimer's disease (AD). To assess the specific role of the pro
      inflammatory cytokine interleukin-1 (IL-1) in AD we examined the effects of intra
      hippocampal transplantation of neural precursor cells (NPCs) with transgenic over
      expression of IL-1 receptor antagonist (IL-1raTG) on memory functioning and
      neurogenesis in a murine model of AD (Tg2576 mice). WT NPCs- or sham-transplanted
      Tg2576 mice, as well as naive Tg2576 and WT mice served as controls. To assess
      the net effect of IL-1 blockade (not in the context of NPCs transplantation), we
      also examined the effects of chronic (4 weeks) intra-cerebroventricular (i.c.v.)
      administration of IL-1ra. We report that 12-month-old Tg2576 mice exhibited
      increased mRNA expression of hippocampal IL-1beta, along with severe disturbances
      in hippocampal-dependent contextual and spatial memory as well as in
      neurogenesis. Transplantation of IL-1raTG NPCs 1 month before the neurobehavioral
      testing completely rescued these disturbances and significantly increased the
      number of endogenous hippocampal cells expressing the plasticity-related molecule
      BDNF. Similar, but less-robust effects were also produced by transplantation of
      WT NPCs and by i.c.v. IL-1ra administration. NPCs transplantation produced
      alterations in hippocampal plaque formation and microglial status, which were not
      clearly correlated with the cognitive effects of this procedure. The results
      indicate that elevated levels of hippocampal IL-1 are causally related to some AD
      associated memory disturbances, and provide the first example for the potential
      use of genetically manipulated NPCs with anti-inflammatory properties in the
      treatment of AD. 

PMID- 23954851
TI  - Antioxidant activity and structural modifications of serum chondroitin sulfate in
      Graves' disease.
AB  - OBJECTIVES: Disturbances in the metabolism of proteoglycans/glycosaminoglycans
      related to free radical overproduction can be detected in Graves' ophthalmopathy.
      However, it is not evident whether these disorders appear before the clinical
      manifestation of ophthalmopathy and contribute to the development of nonthyroidal
      symptoms. They might also reflect the body's defence against the effects of an
      autoimmune attack, or they merely result from these disorders. Our study
      conducted in Graves' patients, free of ocular changes at the time of recruitment,
      is an attempt at explaining these ambiguities. We decided to investigate the
      relation between the changes in extracellular matrix components, namely the total
      glycosaminoglycans (GAGs) and chondroitin sulfates (CS), as well as parameters
      characterising oxidative stress, i.e. the total antioxidant status (TAS), and the
      thiol group (TG) concentration. DESIGN, METHODS, RESULTS: GAGs, TAS and TG were
      quantified in serum samples obtained from 30 healthy subjects and 30 Graves'
      patients before and after treatment. An increased serum concentration of total
      GAGs and CS in Graves' patients before and after treatment was observed.
      Additionally, increased sulfation of CS in both Graves' patient groups was
      recorded. The serum TG and TAS concentrations in untreated patients were
      significantly decreased. Subsequent euthyreosis led to the normalisation of TG
      concentration. We have revealed a significant correlation between changes of
      extracellular matrix components, especially chondroitin-4-sulfate, thyroid status
      parameters, and parameters characterising oxidative stress. CONCLUSIONS: The
      structural modifications of serum CS in Graves' patients clinically free of
      ocular complications are probably the expression of systemic connective tissue
      remodelling. Simultaneously, these modifications may participate in a defence
      response to free radical damage underlying this pathology.

PMID- 23954852
TI  - Evaluation of a straightforward and rapid method for the therapeutic drug
      monitoring of digitoxin by LC-MS/MS.
AB  - OBJECTIVES: Therapeutic drug monitoring of digitoxin is strongly recommended but
      metabolites of digitoxin and digitoxin-like immunoreactive substances may
      interfere with widely used immunoassays. Recently evaluated assays on LC-MS/MS
      have the drawback of long turnaround time. We sought to evaluate a specific
      method on LC-MS/MS optimizing sample preparation thereby significantly reducing
      turnaround time. DESIGN AND METHODS: Linearity, functional sensitivity, and
      precision of the method were established. External quality control samples were
      used for the evaluation of accuracy of the LS-MS/MS method. In addition,
      digitoxin concentrations in 221 samples were measured by LC-MS/MS and
      immunoassay. RESULTS: Linearity was validated between 0.15 and 80 ng/mL. Limit of
      quantification was established at 0.14 ng/mL. Between-day imprecision lay between
      1.4 and 4.9% and meets the conditions required for routine analysis. Comparison
      to results obtained by immunoassay revealed a mean difference of -1.2 ng/mL.
      CONCLUSIONS: By optimizing preparation steps turnaround time was shorter for LC
      MS/MS than for immunoassay. This did not result in increased susceptibility to
      matrix effects. Analytical performance was sufficient for routine analysis.
      Therefore, the method is suitable for routine therapeutic drug monitoring of
      digitoxin.

PMID- 23954853
TI  - Relationship between bone resorption, oxidative stress and inflammation in severe
      COPD exacerbation.
AB  - BACKGROUND: The natural course of chronic obstructive pulmonary disease (COPD) is
      complicated by the development of systemic consequences and co-morbidities.
      Increasing evidence indicates that COPD and osteoporosis are strongly linked. The
      common features in COPD pathology, history of smoking, age, inactivity, systemic
      inflammation, and use of systemic corticosteroids, are important risk factors for
      osteoporosis. METHODS: Pulmonary function, matrix metalloproteinase, tissue
      inhibitor of metalloproteinases, oxidative stress parameters, inflammatory
      markers and bone resorption marker were measured in 85 COPD patients and 47
      healthy subjects. In patients, all parameters were assessed at two time points:
      one day after admission during exacerbation and about 30 days after, in the
      stable state of disease. RESULTS: In patients, bone resorption marker collagen
      type I beta-isomerized C-terminal telopeptide (beta CL) was increased during
      exacerbation: geometric mean 0.521, compared with stable patients 0.408, p<0.01,
      and control subjects 0.362 ng/ml, p<0.001. During exacerbation high sensitivity C
      reactive protein (hsCRP) and neutrophil count were significantly higher in COPD
      patients compared with the control group, p<0.001. Matrix metalloproteinase-9
      (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations were
      significantly higher in COPD patients, stable state or exacerbation, compared
      with control subjects, p<0.001. In patients during exacerbation, total oxidative
      status (TOS) was higher compared with the stable state, p<0.05 and control group,
      p<0.001. Multiple linear regression for the joint influence of inflammation,
      hypoxia and oxidative status during exacerbation showed almost 60% influence on
      the variability of beta CL concentrations. CONCLUSION: Intensification of disease
      characteristic symptoms such as inflammation, hypoxia, protease/antiprotease
      imbalance and oxidative stress, during exacerbation episodes in COPD patients may
      also contribute to increased bone resorption.

PMID- 23954855
TI  - A paramagnetic-reporter two-particle system for amplification-free detection of
      DNA in serum.
AB  - Quantitative nucleic acid detection is used extensively in the management of many
      pathogenic infections, where viral or bacterial nucleic acid copy number relates
      directly to disease prognosis. Temperature-cycle or isothermal amplification
      formats offer excellent performance, but their requirement for purified nucleic
      acid and accurate temperature control increases costs and renders their migration
      to resource-limited environments problematic. In contrast, amplification-free
      nucleic acid assays could allow simplified system design, resulting in reduced
      costs. In this study, we report a amplification-free herpes simplex virus (HSV)
      assay where oligoethylene glycol methacrylate (OEGMA) grafted ssDNA capture
      probes on paramagnetic nanoparticles are coupled with reporter-probe-modified
      fluorescent nanoparticles in a target-dependent manner. Following assay and
      reagent optimization, a sub-pM (25 amol) limit of detection could be achieved in
      buffer and also in neat, undiluted serum, representing a 160-fold improvement
      over that achieved using convention detection with a fluorescence plate reader.
      Equivalent performance in serum and buffer offers the opportunity for simplified
      diagnostic device design for resource-limited environments.

PMID- 23954856
TI  - The ArrayGrid: a methodology for applying multiple samples to a single TEM
      specimen grid.
AB  - High throughput transmission electron microscopy (TEM) is limited by the time
      that it takes to prepare each specimen and insert it on the microscope. It is
      further impeded by the deteriorating vacuum of the microscope upon frequent
      specimen cycling. Nevertheless, in most cases only a small fraction of the
      specimen is examined and sufficient to provide hundreds of images. Here we
      demonstrate that microarray technology can be used to accurately position
      picoliter quantities of different samples in a single TEM grid, with negligible
      cross-contamination. Key features are a contact-mode deposition on a robust
      formvar-carbon support. The TEM grid containing a microarray of different
      samples, the ArrayGrid, can also be negatively stained. The ArrayGrid increases
      the efficiency of TEM grid preparation and examination by at least by one order
      of magnitude, and is very suitable for screening and data collection especially
      in experiments that generate a multiplicity of samples. 

PMID- 23954857
TI  - Loss of CB1 receptors leads to decreased cathepsin D levels and accelerated
      lipofuscin accumulation in the hippocampus.
AB  - Early onset of age-related changes in the brain of cannabinoid 1 receptor
      knockout (Cnr1(-/-)) mice suggests that cannabinoid 1 (CB1) receptor activity
      significantly influences the progression of brain aging. In the present study we
      show that lack of CB1 receptors leads to a significant increase in lipofuscin
      accumulation and a reduced expression and activity of cathepsin D, lysosomal
      protease implicated in the degradation of damaged macromolecules, in the
      hippocampus of 12-month-old mice. The impaired clearance of damaged
      macromolecules due to the low cathepsin D levels and not enhanced oxidative
      stress may be responsible for the lipofuscin accumulation because macromolecule
      oxidation levels were comparable between the genotypes within the same age group.
      The altered levels of autophagy markers p62 and LC3-II suggest that autophagy is
      upregulated in CB1 knockout mice. Increased autophagic flux in the absence of CB1
      receptors is probably a compensatory mechanism to partially counteract decreased
      lysosomal degradation capacity. Together, these results suggest that CB1 receptor
      activity affects lysosomal activity, degradation of damaged macromolecules and
      thus it may influence the course and onset of brain aging. 

PMID- 23954858
TI  - Galectin-1 induces 12/15-lipoxygenase expression in murine macrophages and favors
      their conversion toward a pro-resolving phenotype.
AB  - During the resolution of inflammation macrophages undergo functional changes upon
      exposure to pro-resolving agents in their microenvironment. Primarily, engulfment
      of apoptotic polymorphonuclear (PMN) cells promotes conversion of macrophages
      toward a pro-resolving phenotype characterized by reduced CD11b expression. These
      macrophages are not phagocytic, do not respond to TLR ligands, and express
      relatively high levels of the pro-resolving enzyme 12/15-lipoxygenase (LO). Here,
      we report that the immuno-regulatory lectin galectin-1 is selectively expressed
      by CD11b(high), but not CD11b(low) macrophages. Upon exposure in vivo and ex
      vivo, galectin-1 directly promoted macrophage conversion from a CD11b(high) to a
      CD11b(low) phenotype and up-regulated the expression and activity of 12/15-LO.
      Moreover, galectin-1 treatment in vivo promoted the loss of phagocytic capacity
      (efferocytic satiation) in peritoneal macrophages and down-regulated secretion of
      TNF-alpha, IL-1beta, and IL-10 upon LPS exposure. Our results suggest that
      galectin-1 could be an essential mediator in the control of macrophage function
      during the resolution of inflammation. 

PMID- 23954859
TI  - The thioredoxin system in the dental caries pathogen Streptococcus mutans and the
      food-industry bacterium Streptococcus thermophilus.
AB  - The Streptococcus genus includes the pathogenic species Streptococcus mutans, the
      main responsible of dental caries, and the safe microorganism Streptococcus
      thermophilus, used for the manufacture of dairy products. These facultative
      anaerobes control the levels of reactive oxygen species (ROS) and indeed, both S.
      mutans and S. thermophilus possess a cambialistic superoxide dismutase, the key
      enzyme for a preventive action against ROS. To evaluate the properties of a
      crucial mechanism for repairing ROS damages, the molecular and functional
      characterization of the thioredoxin system in these streptococci was
      investigated. The putative genes encoding its protein components in S. mutans and
      S. thermophilus were analysed and the corresponding recombinant proteins were
      purified. A single thioredoxin reductase was obtained from either S. mutans
      (SmTrxB) or S. thermophilus (StTrxB1), whereas two thioredoxins were prepared
      from either S. mutans (SmTrxA and SmTrxH1) or S. thermophilus (StTrxA1 and
      StTrxA2). Both SmTrxB and StTrxB1 reduced the synthetic substrate DTNB in the
      presence of NADPH, whereas only SmTrxA and StTrxA1 accelerated the insulin
      reduction in the presence of DTT. To reconstitute an in vitro streptococcal
      thioredoxin system, the combined activity of the thioredoxin components was
      tested through the insulin precipitation in the absence of DTT. The assay
      functions with a combination of SmTrxB or StTrxB1 with either SmTrxA or StTrxA1.
      These results suggest that the streptococcal members of the thioredoxin system
      display a direct functional interaction between them and that these protein
      components are interchangeable within the Streptococcus genus. In conclusion, our
      data prove the existence of a functioning thioredoxin system even in these
      microaerophiles.

PMID- 23954860
TI  - An active site mutant of Escherichia coli cyclopropane fatty acid synthase forms
      new non-natural fatty acids providing insights on the mechanism of the enzymatic
      reaction.
AB  - We have produced and purified an active site mutant of the Escherichia coli
      cyclopropane fatty acid synthase (CFAS) by replacing the strictly conserved G236
      within cyclopropane synthases, by a glutamate residue, which corresponds to E146
      of the homologous mycolic acid methyltransferase, Hma, producing hydroxymethyl
      mycolic acids. The G236E CFAS mutant had less than 1% of the in vitro activity of
      the wild type enzyme. We expressed the G236E CFAS mutant in an E. coli (DE3)
      strain in which the chromosomal cfa gene had been deleted. After extraction of
      phospholipids and conversion into the corresponding fatty acid methyl esters
      (FAMEs), we observed the formation of cyclopropanated FAMEs suggesting that the
      mutant retained some of the normal activity in vivo. However, we also observed
      the formation of new C17 methyl-branched unsaturated FAMEs whose structures were
      determined using GC/MS and NMR analyses. The double bond was located at different
      positions 8, 9 or 10, and the methyl group at position 10 or 9. Thus, this new
      FAMEs are likely arising from a 16:1 acyl chain of a phospholipid that had been
      transformed by the G236E CFAS mutant in vivo. The reaction catalyzed by this
      G236E CFAS mutant thus starts by the methylation of the unsaturated acyl chain at
      position 10 or 9 yielding a carbocation at position 9 or 10 respectively. It
      follows then two competing steps, a normal cyclopropanation or hydride
      shift/elimination events giving different combinations of alkenes. This study not
      only provides further evidence that cyclopropane synthases (CSs) form a
      carbocationic intermediate but also opens the way to CSs engineering for the
      synthesis of non-natural fatty acids.

PMID- 23954861
TI  - Programmed necrosis, not apoptosis, is a key mediator of cell loss and DAMP
      mediated inflammation in dsRNA-induced retinal degeneration.
AB  - There is no known treatment for the dry form of an age-related macular
      degeneration (AMD). Cell death and inflammation are important biological
      processes thought to have central role in AMD. Here we show that receptor
      interacting protein (RIP) kinase mediates necrosis and enhances inflammation in a
      mouse model of retinal degeneration induced by dsRNA, a component of drusen in
      AMD. In contrast to photoreceptor-induced apoptosis, subretinal injection of the
      dsRNA analog poly(I : C) caused necrosis of the retinal pigment epithelium (RPE),
      as well as macrophage infiltration into the outer retinas. In Rip3(-/-) mice,
      both necrosis and inflammation were prevented, providing substantial protection
      against poly(I : C)-induced retinal degeneration. Moreover, after poly(I : C)
      injection, Rip3(-/-) mice displayed decreased levels of pro-inflammatory
      cytokines (such as TNF-alpha and IL-6) in the retina, and attenuated intravitreal
      release of high-mobility group box-1 (HMGB1), a major damage-associated molecular
      pattern (DAMP). In vitro, poly(I : C)-induced necrosis were inhibited in Rip3
      deficient RPE cells, which in turn suppressed HMGB1 release and dampened TNF
      alpha and IL-6 induction evoked by necrotic supernatants. On the other hand, Rip3
      deficiency did not modulate directly TNF-alpha and IL-6 production after poly(I :
      C) stimulation in RPE cells or macrophages. Therefore, programmed necrosis is
      crucial in dsRNA-induced retinal degeneration and may promote inflammation by
      regulating the release of intracellular DAMPs, suggesting novel therapeutic
      targets for diseases such as AMD. 

PMID- 23954863
TI  - The global identification of tRNA isoacceptors by targeted tandem mass
      spectrometry.
AB  - Transfer ribonucleic acids (tRNA) are a biologically significant class of non
      coding ribonucleic acids (ncRNAs) that pose unique analytical challenges for
      complete characterization. Here we present a robust and simple method for the
      consistent and accurate identification of individual tRNAs from a pool of total
      tRNA obtained from cell lysate. Through this method individual isoacceptor tRNAs
      are identified by the detection of unique oligonucleotide sequences which arise
      from a single enzymatic digestion. These unique sequences can be detected by
      monitoring specific transitions from precursor to product ions. Thus, for any
      pool of known tRNA sequences including posttranscriptional modifications,
      targeted tandem mass spectrometry can be used for monitoring these specific
      transitions. The proposed method was developed and validated using a set of known
      tRNAs from Escherichia coli. This approach was found to identify 41 +/- 2 of the
      predicted 47 isoaccepting tRNAs in E. coli from targeted tandem mass spectrometry
      using only 24 precursor m/z values. This method should be easily adapted to other
      bacterial systems for both genomic and posttranscriptional analysis of tRNAs, and
      is likely suitable for future clinical applications. 

PMID- 23954864
TI  - Facile one-pot synthesis of spherical zinc sulfide-carbon nanocomposite powders
      with superior electrochemical properties as anode materials for Li-ion batteries.
AB  - A novel and simple one-pot method of systematically synthesizing spherical metal
      sulfide-carbon composite powders is reported for the first time. The zinc sulfide
      carbon composite is selected as the first target material. The prepared composite
      powders show superior electrochemical properties as anode materials for lithium
      ion batteries. 

PMID- 23954862
TI  - Increasing diversity of neural responses to speech sounds across the central
      auditory pathway.
AB  - Neurons at higher stations of each sensory system are responsive to feature
      combinations not present at lower levels. As a result, the activity of these
      neurons becomes less redundant than lower levels. We recorded responses to speech
      sounds from the inferior colliculus and the primary auditory cortex neurons of
      rats, and tested the hypothesis that primary auditory cortex neurons are more
      sensitive to combinations of multiple acoustic parameters compared to inferior
      colliculus neurons. We independently eliminated periodicity information, spectral
      information and temporal information in each consonant and vowel sound using a
      noise vocoder. This technique made it possible to test several key hypotheses
      about speech sound processing. Our results demonstrate that inferior colliculus
      responses are spatially arranged and primarily determined by the spectral energy
      and the fundamental frequency of speech, whereas primary auditory cortex neurons
      generate widely distributed responses to multiple acoustic parameters, and are
      not strongly influenced by the fundamental frequency of speech. We found no
      evidence that inferior colliculus or primary auditory cortex was specialized for
      speech features such as voice onset time or formants. The greater diversity of
      responses in primary auditory cortex compared to inferior colliculus may help
      explain how the auditory system can identify a wide range of speech sounds across
      a wide range of conditions without relying on any single acoustic cue. 

PMID- 23954865
TI  - Detecting variations of blood volume shift due to heart beat from respiratory
      inductive plethysmography measurements in man.
AB  - The simultaneous study of the cardiac and respiratory activities and their
      interactions is of great physiological and clinical interest. For this purpose,
      we want to investigate if respiratory inductive plethysmography (RIP) can be used
      for cardiac functional exploration. We propose a system, based on RIP technology
      and time-scale approaches of signal processing, for the extraction of cardiac
      information. This study focuses on the monitoring of blood volume shift due to
      heart beat, noted ?Vtr_c and investigates RIP for the detection of ?Vtr_c
      variations by comparison to stroke volume (SV) variations estimated by impedance
      cardiography (IMP). We proposed a specific respiratory protocol assumed to induce
      significant variations of the SV. Fifteen healthy volunteers in the seated and
      supine positions were asked to alternate rest respiration and maneuvers,
      consisting in blowing into a manometer. A multi-step treatment including a
      variant of empirical mode decomposition was applied on RIP signals to extract
      cardiac volume signals and estimate beat-to-beat ?Vtr_c. These were averaged in
      quasi-stationary states at rest and during the respiratory maneuvers, and
      analysed in view of SV estimations from IMP signals simultaneously acquired.
      Correlation and statistical tests over the data show that RIP can be used to
      detect variations of the cardiac blood shift in healthy young subjects. 

PMID- 23954866
TI  - Gene-environment and gene-gene interactions of specific MTHFR, MTR and CBS gene
      variants in relation to homocysteine in black South Africans.
AB  - The methylenetetrahydrofolate reductase (MTHFR), cystathione-beta-synthase (CBS)
      and methionine synthase (MTR) genes interact with each other and the environment.
      These interactions could influence homocysteine (Hcy) and diseases contingent
      thereon. We determined single nucleotide polymorphisms (SNPs) within these genes,
      their relationships and interactions with total Hcy concentrations within black
      South Africans to address the increased prevalence of diseases associated with
      Hcy. The MTHFR 677 TT and MTR 2756 AA genotypes were associated with higher Hcy
      concentrations (16.6 and 10.1 MUmol/L; p<0.05) compared to subjects harboring the
      MTHFR 677 CT/CC and the MTR 2756 AG genotypes (10.5, 9.7 and 9.5 MUmol/L,
      respectively). The investigated CBS genotypes did not influence Hcy. We
      demonstrated interactions between the area of residence and the CBS
      T833C/844ins68 genotypes (p=0.005) so that when harboring the wildtype allele,
      rural subjects had significantly higher Hcy than their urban counterparts, but
      when hosting the variant allele the environment made no difference to Hcy.
      Between the CBS T833C/844ins68 or G9276A and MTHFR C677T genotypes, there were
      two-way interactions (p=0.003 and=0.004, respectively), with regard to Hcy.
      Subjects harboring the MTHFR 677 TT genotype in combination with the CBS 833
      TT/homozygous 844 non-insert or the MTHFR 677 TT genotype in combination with the
      CBS 9276 GA/GG displayed higher Hcy concentrations. Therefore, some of the
      investigated genotypes affected Hcy; residential area changed the way in which
      the CBS T833C/844ins68 SNPs influenced Hcy concentrations highlighting the
      importance of environmental factors; and gene-gene interactions allude to
      epistatic effects.

PMID- 23954867
TI  - The association of idiopathic recurrent pregnancy loss with polymorphisms in
      hemostasis-related genes.
AB  - Recurrent pregnancy loss (RPL) is a complex, multifactorial condition. Inherited
      thrombophilia is the leading cause of thromboembolism and is associated with an
      increased risk of RPL. The aims of the current study were to investigate the
      effects of polymorphisms in hemostasis-related genes antithrombin (SERPINC1),
      thrombomodulin (THBD), tissue factor pathway inhibitor (TFPI), factor V, factor
      II and annexin A5 (ANXA5), involved in reproductive failure in 94 RPL cases with
      two or more consecutive pregnancy losses prior to 20weeks of pregnancy and 169
      healthy controls who had at least one term delivery and no history of pregnancy
      loss. The genotypes of SERPINC1 G786A, THBD C1418T, TFPI T-33C, factor V G1628A,
      factor II A19911G and ANXA5 G76A were assayed by the Sequenom MassARRAY system.
      Genotype and allele frequencies for SERPINC1 (rs2227589), TFPI (rs8176592),
      factor V (rs6020), factor II (rs3136516) and ANXA5 (rs113588187) in cases and
      controls were similar. The distribution of THBD C1418T allele showed significant
      differences between RPL cases and healthy controls (odds ratio (OR): 1.58, 95%,
      confidence interval (CI): 1.05-2.39, P=0.027). In univariate logistic regression
      analyses, carriers of THBD 1418T allele (CT+TT) had an increased risk of RPL (OR:
      1.83, 95%, CI: 1.10-3.06, P=0.020). This indicated that THBD 1418T allele was
      associated with increasing the risk of RPL.

PMID- 23954868
TI  - Lack of association between genetic polymorphisms in ROBO1, MRPL19/C2ORF3 and
      THEM2 with developmental dyslexia.
AB  - Developmental Dyslexia (DD) is a heritable, complex genetic disorder
      characterized by specific impairment in reading and writing ability that is
      substantially below the expected reading ability given the person's chronological
      age, measured intelligence and age-appropriate education. More than ten
      susceptible genes have been identified for DD. A Single Nucleotide Polymorphism
      (SNP) of these genes was found to be associated with various phenotypes of DD. To
      identify the role of SNPs of four candidate genes namely, MRPL19/C2ORF3, ROBO1
      and THEM2 in an Indian population, we genotyped eight SNPs of these genes in 157
      children with DD and 212 normal readers using a MassARRAY technique with a MALDI
      TOF MS analyzer. Power analysis of some of these SNPs showed >80% of power. Chi
      square test, Odds Ratios (ORs), 95% Confidence Intervals (CIs) and Bonferroni's
      correction were applied to identify the significance of the genotyped SNPs and
      haplotypes. Our study failed to show any association of SNPs and haplotypes of
      these genes with DD in an Indian population. 

PMID- 23954870
TI  - The impact of reactive oxygen species and genetic mitochondrial mutations in
      Parkinson's disease.
AB  - The exact pathogenesis of Parkinson's disease (PD) is still unknown and proper
      mechanisms that correspond to the disease remain unidentified. It is understood
      that PD is age-related; as age increases, the chance of onset responds
      accordingly. Although there are no current means of curing PD, the understanding
      of reactive oxygen species (ROS) provides significant insight to possible
      treatments. Complex I deficiencies of the respiratory chain account for the
      majority of unfavorable neural apoptosis generation in PD. Dopaminergic neurons
      are severely damaged as a result of the deficiency. Symptoms such as inhibited
      cognitive ability and loss of smooth motor function are the results of such
      impairment. The genetic mutations of Parkinson's related proteins such as PINK1
      and LRRK2 contribute to mitochondrial dysfunction which precedes ROS formation.
      Various pathways are inhibited by these mutations, and inevitably causing neural
      cell damage. Antioxidants are known to negate the damaging effects of free
      radical overexpression. This paper expands on the specific impact of
      mitochondrial genetic change and production of free radicals as well as its
      correlation to the neurodegeneration in Parkinson's disease. 

PMID- 23954869
TI  - A CRYGC gene mutation associated with autosomal dominant pulverulent cataract.
AB  - PURPOSE: To describe at molecular level a family with pulverulent congenital
      cataract associated with a CRYGC gene mutation. METHODS: One family with several
      affected members with pulverulent congenital cataract and 230 healthy controls
      were examined. Genomic DNA from leukocytes was isolated to analyze the CRYGA-D
      cluster, CX46, CX50 and MIP genes through high-resolution melting curve and DNA
      sequencing. RESULTS: DNA sequencing in the affected members revealed the c.143G>A
      mutation (p.R48H) in exon 2 of the CRYGC gene; 230 healthy controls and ten
      healthy relatives were also analyzed and none of them showed the c.143G>A
      mutation. No other polymorphisms or mutations were found to be present.
      CONCLUSION: In the present study, we described a family with pulverulent
      congenital cataract that segregated the c.143G>A mutation (p.R48H) in the CRYGC
      gene. A few mutations have been described in the CRYGC gene in autosomal dominant
      cataract, none of them with pulverulent cataract making clear the clinical
      heterogeneity of congenital cataract. This mutation has been associated with the
      phenotype of congenital cataract but also is considered an SNP in the NCBI data
      base. Our data and previous report suggest that p.R48H could be a disease-causing
      mutation and not an SNP.

PMID- 23954871
TI  - Influence of interleukin-6 gene -174G>C polymorphism on development of
      atherosclerosis: a meta-analysis of 50 studies involving 33,514 subjects.
AB  - Increasing epidemiological studies have focused on the associations between
      interleukin-6 (IL-6) gene -174G>C polymorphism and atherosclerotic diseases, but
      the results are still controversial. This meta-analysis was designed to identify
      whether this association exists. PubMed, Embase, Web of Science, Cochrane
      database, Clinicaltrials.gov and Current Controlled Trials, Chinese Clinical
      Trial Registry, CBMdisc, CNKI and Google Scholar were searched to get the genetic
      association studies. The crude odds ratios (ORs) and their corresponding 95%
      confidence intervals (CIs) were used to estimate the association between the IL-6
      gene -174G>C polymorphism and atherosclerosis ( AS ) risk. The subgroup analyses
      were made on the following: ethnicity, atherosclerotic diseases and source of
      controls. Finally, 50 studies (15,029 cases and 18,485 controls) were included in
      this meta-analysis. Overall, no significant association was found between the IL
      6 gene -174G>C polymorphism and AS risk (for C allele vs. G allele: OR=1.02, 95%
      CI=0.94-1.11, p=0.64; for C/C vs. G/G: OR=1.01, 95% CI=0.85-1.21, p=0.88; for C/C
      vs. C/G+G/G: OR=0.97, 95% CI=0.84-1.12, p=0.68; for C/C+C/G vs. G/G: OR=1.07, 95%
      CI=0.97-1.17, p=0.18). In the subgroup analyses, significant associations were
      found between the IL-6 gene -174G>C polymorphism and AS in non-Caucasian group
      (for CC+CG vs. GG: OR=1.22, 95% CI=1.06-1.41, p=0.005), other atherosclerotic
      diseases group (for C allele vs. G allele: OR =0.75, 95% CI=0.61-0.93, p=0.008;
      for C/C vs. G/G: OR=0.56, 95% CI=0.38-0.81, p=0.002; for C/C vs. C/G+G/G:
      OR=0.60, 95% CI=0.45-0.79, p=0.0004) and population-based group (for C allele vs.
      G allele: OR=1.09, 95% CI=1.00-1.18, p=0.04; for CC+CG vs. GG: OR=1.15, 95%
      CI=1.04-1.27, p=0.005). In summary, the present meta-analysis suggests that the
      IL-6 gene -174G C polymorphism is associated with the susceptibility to AS.
      However, due to the high heterogeneity in the meta-analysis, the results should
      be interpreted with caution.

PMID- 23954872
TI  - Single nucleotide polymorphisms in the mitochondrial control region are
      associated with metabolic phenotypes and oxidative stress.
AB  - OBJECTIVE: To identify the mitochondrial DNA (mtDNA) single nucleotide
      polymorphisms (SNPs) in the control region and elucidate their role in metabolic
      phenotypes and oxidative stress. METHODS: A total of 861 nondiabetic subjects
      were enrolled, including 250 impaired fasting glucose (IFG) and 370 obese
      subjects (body mass index [BMI]>25 kg/m(2)). Antioxidant status presented as
      total free thiol level was determined from serum samples. DNA was extracted from
      peripheral blood leucocytes, and the sequences were analyzed using the DNASTAR
      software. SNPs were identified by comparison with the Cambridge Reference
      Sequence. RESULTS: After adjusting odds ratios for age, sex, and BMI, the
      selected independently significant SNPs indicated 4 susceptible SNPs: SNP-16126C
      and SNP-16261T, which were related to abdominal obesity (P=0.009; 0.06); SNP
      16390A, related to hypertension (HTN) (P=0.007); and SNP-16092C, related to
      decreased antioxidant capacity (P=0.015). In the obese subgroup, 3 susceptible
      SNPs included SNP-16189C and SNP-16260T, which showed significantly higher IFG
      prevalence (P=0.016 and 0.024, respectively), and SNP-16519C, which was
      significantly higher in the HTN group (P=0.036). As to protective SNPs, 5
      protective SNPs were identified in all subjects but only one SNP-16093C is
      consistent in obese group, which showed a significantly lower prevalence in
      patients with abdominal obesity and was associated with a higher antioxidant
      status (P<0.001). CONCLUSION: SNPs in the mtDNA control region are associated
      with metabolic phenotypes and oxidative stress markers. Some SNPs are relating to
      the interaction between obesity and genetic factors. The beneficial effects of
      these protective SNPs were insignificant and some susceptible SNPs became
      dominant within the obese subgroup. Subjects harboring these SNPs should avoid
      excessive weight gain.

PMID- 23954873
TI  - Characterization of the complete mitochondrial genome of Tryporyza incertulas, in
      comparison with seven other Pyraloidea moths.
AB  - The complete 15,223-bp mitochondrial genome (mitogenome) of Tryporyza incertulas
      (Walker) (Lepidoptera: Pyraloidea: Crambidae) was determined, characterized and
      compared with seven other species of superfamily Pyraloidea. The order of 37
      genes was typical of insect mitochondrial DNA sequences described to date.
      Compared with other moths of Pyraloidea, the A+T biased (77.0%) of T. incertulas
      was the lowest. Eleven protein-coding genes (PCGs) utilized the standard ATN, but
      cox1 used CGA and nad4 used AAT as the initiation codons. Ten protein-coding
      genes had the common stop codon TAA, except nad3 having TAG as the stop codon,
      and cox2, nad4 using T, TA as the incomplete stop codons, respectively. All of
      the tRNA genes had typical cloverleaf secondary structures except trnS1(AGN), in
      which the dihydrouridine (DHU) arm did not form a stable stem-loop structure.
      There was a spacer between trnQ and nad2, which was common in Lepidoptera moths.
      A 6-bp motif 'ATACTA' between trnS2(UCN) and nad1, a 7-bp motif "AGC(T)CTTA"
      between trnW and trnC and a 6-bp motif "ATGATA" of overlapping region between
      atp8 and atp6 were found in Pyraloidea moths. The A+T-rich region contained an
      'ATAGT(A)'-like motif followed by a poly-T stretch. In addition, two potential
      stem-loop structures, a duplicated 19-bp repeat element, and two microsatellites
      '(TA)12' and '(TA)9' were observed in the A+T-rich region of T. incertulas
      mitogenome. Finally, the phylogenetic relationships of Pyraloidea species were
      constructed based on amino acid sequences of 13 PCGs of mitogenomes using
      Bayesian inference (BI) and maximum likelihood (ML) methods. These molecular
      based phylogenies supported the morphological classification on relationships
      within Pyraloidea species.

PMID- 23954874
TI  - Regulation of human autoimmune regulator (AIRE) gene translation by miR-220b.
AB  - Although mutations of autoimmune regulator (AIRE) gene are responsible for
      autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED),
      presenting a wide spectrum of many characteristic and non-characteristic clinical
      features, some patients lack AIRE gene mutations. Therefore, something other than
      a mutation, such as dysregulation of AIRE gene, may be a causal factor for APECED
      or its related diseases. However, regulatory mechanisms for AIRE gene expression
      and/or translation have still remained elusive. We found that IL-2-stimulated
      CD4(+) T (IL-2T) cells showed a high expression of AIRE gene, but very low AIRE
      protein production, while Epstein-Barr virus-transformed B (EBV-B) cells express
      both AIRE gene and AIRE protein. By using microarray analysis, we could identify
      miR-220b as a possible regulatory mechanism for AIRE gene translation in IL-2T
      cells. Here we report that miR-220b significantly reduced the expression of AIRE
      protein in AIRE gene with 3'UTR region transfected 293T cells, whereas no
      alteration of AIRE protein production was observed in the open reading frame of
      AIRE gene alone transfected cells. In addition, anti-miR-220b reversed the
      inhibitory function of miR-220b for the expression of AIRE protein in AIRE gene
      with 3'UTR region transfected cells. Moreover, when AIRE gene transfected cells
      with mutated 3'UTR were transfected with miR-220b, no reduction of AIRE protein
      production was observed. Taken together, it was concluded that miR-220b inhibited
      the AIRE gene translation through the 3'UTR region of AIRE gene, indicating that
      miR-220b could serve as a regulator for human AIRE gene translation.

PMID- 23954876
TI  - Pike and salmon as sister taxa: detailed intraclade resolution and divergence
      time estimation of Esociformes + Salmoniformes based on whole mitochondrial
      genome sequences.
AB  - The increasing number of taxa and loci in molecular phylogenetic studies of basal
      euteleosts has brought stability in a controversial area. A key emerging aspect
      to these studies is a sister Esociformes (pike) and Salmoniformes (salmon)
      relationship. We evaluate mitochondrial genome support for a sister Esociformes
      and Salmoniformes hypothesis by surveying many potential outgroups for these
      taxa, employing multiple phylogenetic approaches, and utilizing a thorough
      sampling scheme. Secondly, we conduct a simultaneous divergence time estimation
      and phylogenetic inference in a Bayesian framework with fossil calibrations
      focusing on relationships within Esociformes+Salmoniformes. Our dataset supports
      a sister relationship between Esociformes and Salmoniformes; however the nearest
      relatives of Esociformes+Salmoniformes are inconsistent among analyses. Within
      the order Esociformes, we advocate for a single family, Esocidae. Subfamily
      relationships within Salmonidae are poorly supported as Salmoninae sister to
      Thymallinae+Coregoninae.

PMID- 23954875
TI  - Onset of rosette formation during spontaneous neural differentiation of hESC and
      hiPSC colonies.
AB  - In vitro neural differentiation of human embryonic stem cells (hESCs) is an
      advantageous system for studying early neural development. The process of early
      neural differentiation in hESCs begins by initiation of primitive neuroectoderm,
      which is manifested by rosette formation, with consecutive differentiation into
      neural progenitors and early glial-like cells. In this study, we examined the
      involvement of early neural markers - OTX2, PAX6, Sox1, Nestin, NR2F1, NR2F2, and
      IRX2 - in the onset of rosette formation, during spontaneous neural
      differentiation of hESC and human induced pluripotent stem cell (hiPSC) colonies.
      This is in contrast to the conventional way of studying rosette formation, which
      involves induction of neuronal differentiation and the utilization of embryoid
      bodies. Here we show that OTX2 is highly expressed at the onset of rosette
      formation, when rosettes comprise no more than 3-5 cells, and that its expression
      precedes that of established markers of early neuronal differentiation.
      Importantly, the rise of OTX2 expression in these cells coincides with the down
      regulation of the pluripotency marker OCT4. Lastly, we show that cells derived
      from rosettes that emerge during spontaneous differentiation of hESCs or hiPSCs
      are capable of differentiating into dopaminergic neurons in vitro, and into
      mature-appearing pyramidal and serotonergic neurons weeks after being injected
      into the motor cortex of NOD-SCID mice. 

PMID- 23954877
TI  - Core promoter analysis of porcine Six1 gene and its regulation of the promoter
      activity by CpG methylation.
AB  - Six1, an evolutionary conserved transcription factor, has been shown to play an
      important role in organogenesis and diseases. However, no reports were shown to
      investigate its transcriptional regulatory mechanisms. In the present study, we
      first identified porcine Six1 gene core promoter region (+170/-360) using
      luciferase reporter assay system and found that promoter activities were
      significantly higher in the mouse myoblast C2C12 cells than that in the mouse
      fibroblast C3H10T1/2 cells, implying that Six1 promoter could possess muscle
      specific characteristics. Moreover, our results showed that promoter activities
      of Six1 were decreased as induction of differentiation of C2C12 cells, which was
      accompanied by the down-regulation of mRNA expression of Six1 gene. In addition,
      we found that the DNA methylation of Six1 promoters in vitro obviously influences
      the promoter activities and the DNA methylation level of Six1 promoter core
      region was negatively correlated to Six1 gene expression in vivo. Taken together,
      we preliminarily clarified transcriptional regulatory mechanisms of Six1 gene,
      which should be useful for investigating its subtle transcriptional regulatory
      mechanisms in the future. On the other hand, based on Six1 involved in
      tumorigenesis, our data also provide a genetic foundation to control the
      generation of diseases via pursuing Six1 as therapeutic target gene. 

PMID- 23954878
TI  - Molecular evolution and diversity of dimeric alpha-amylase inhibitor gene in
      Kengyilia species (Triticeae: Poaceae).
AB  - Kengyilia Yen et J. L. Yang is a group of allohexaploid species with StYP genomic
      constitutions in the wheat tribe. To investigate the evolution and diversity of
      dimeric alpha-amylase inhibitor genes in the Kengyilia, forty-five homoeologous
      DAAI gene sequences were isolated from sampled Kengyilia species and analyzed
      together with those of its close relatives. These results suggested that (1)
      Kengyilia species from Central Asia and the Qinghai-Tibetan Plateau had different
      origins from those of the geographically differentiated P genome; (2) the St and
      P genomes of Kengyilia were donated by Pseudoroegneria and Agropyron,
      respectively, and the Y genome had an independent origin and showed an affinity
      with the St genome; (3) purifying selection dominated the DAAI gene members and
      the St-DAAI gene was evolving at faster rate than the P- and Y-DAAI genes in
      Kengyilia; and (4) natural selection was the main factor on the codon usage
      pattern of the DAAI gene in Kengyilia. 

PMID- 23954879
TI  - A genetic variant in pre-miR-27a is associated with a reduced breast cancer risk
      in younger Chinese population.
AB  - Accumulating evidence has indicated that single nucleotide polymorphisms (SNPs)
      in miRNA precursors may have an effect on miRNA expression levels. Recently, an
      important A to G transition SNP in pre-mir-27a (rs895819) was identified.
      Previous studies have investigated the role of rs895819 in cancer risk, but the
      results remain contradictory, rather than conclusive. The present study aimed to
      evaluate the association of rs895819 with sporadic breast cancer susceptibility,
      clinicopathological characteristics and prognosis. We first analyzed the
      influence of rs895819 on the miR-27a expression level and determined that miR-27a
      expression was significantly lower in samples with the AG/GG genotype compared to
      samples with the AA genotype (p=0.022). Further investigation revealed that
      subjects with the G allele exhibited a significantly decreased risk of breast
      cancer relative to subjects carrying the A allele among the younger population
      (adjusted OR=0.628, 95% confidence interval 0.410-0.961; p=0.032). Moreover,
      significant associations between the presence of rs895819 and the histological
      grade and estrogen status of breast cancers were observed among the older group.
      However, the SNP did not influence the survival rate of patients with breast
      cancer. In conclusion, our results suggest that the SNP rs895819 may serve as a
      risk factor for breast cancer in younger Chinese populations; however, larger
      population-based studies are needed to validate these findings. 

PMID- 23954881
TI  - Methylenetetrahydrofolate reductase C677T mutation in patients with alopecia
      areata in Turkish population.
AB  - OBJECTIVE: Methylene-tetrahydrofolate reductase (MTHFR) is a key enzyme
      regulating folate metabolism and it is thought to influence DNA methylation and
      nucleic acid synthesis. Mutations in the MTHFR gene have been associated with
      several autoimmune disorders in previous studies. Alopecia areata (AA) is
      considered to be a tissue-specific autoimmune disease as the hair follicle has
      been targeted and antibodies to their own hair follicle structures have been
      developed. Since there is a common shared pathway between AA and other autoimmune
      disorders, we aimed to investigate a possible association between the MTHFR gene
      C677T mutation and AA susceptibility in the Turkish population. METHODS: The
      study included 136 patients affected by AA and 130 healthy controls. Genomic DNA
      was isolated and genotyped using a polymerase chain reaction (PCR)-based
      restriction fragment length polymorphism (RFLP) assay for the MTHFR gene C677T
      mutation. RESULTS: The distributions of genotype and allele frequencies of MTHFR
      gene C677T mutation were statistically different between AA patients and the
      control group (p=0.036 and p=0.011, respectively). High differences were also
      observed when the patients and controls were compared according to CC versus
      CT+TT (p=0.012). CT+TT genotypes and T allele of MTHFR gene C677T mutation were
      found to be a susceptibility factor for AA in the Turkish population. CONCLUSION:
      The results suggest that MTHFR gene C677T mutation may have an effect on the risk
      of alopecia areata in the Turkish population. This is the first study reporting
      the association between the MTHFR (C677T) genotype and AA.

PMID- 23954880
TI  - Single nucleotide polymorphism of CD40 in the 5'-untranslated region is
      associated with ischemic stroke.
AB  - OBJECTIVES: Ischemic stroke is influenced by both environmental and genetic
      factors. The CD40/CD40L system is related to proinflammatory and prothrombogenic
      responses, which are involved in the pathophysiology of ischemic stroke. The aim
      of this study was to evaluate association between the CD40 -1C/T single
      nucleotide polymorphism (SNP) and ischemic stroke in a Chinese population.
      METHODS: We conducted a case-control study including 286 ischemic stroke patients
      and 336 controls. CD40 -1C/T SNP was genotyped using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods,
      and evaluated its relevance to ischemic stroke susceptibility. RESULTS:
      Significantly increased ischemic stroke risk was found to be associated with the
      T allele of CD40 -1C/T (OR=1.273, 95% CI=1.016-1.594). The frequencies of CT and
      TT/CT genotypes of CD40 -1C/T in ischemic stroke patients were significantly
      higher than those of controls, respectively (for CT: OR=2.350, 95% CI=1.601
      3.449; for TT/CT: OR=2.148, 95% CI=1.479-3.119). And, similar results were
      obtained after adjusting non-matched variables. We found that the frequency of
      carried T genotypes (TT and TT/CT) was significantly increased in patients with
      history of stroke compared with patients without (for TT: OR=6.538, 95%CI=1.655
      25.833; for TT/CT: OR=3.469, 95%CI=1.031-11.670), respectively. CONCLUSIONS: The
      findings suggested that the CD40 -1C/T polymorphism might contribute to the
      susceptibility to ischemic stroke in the Chinese population, and might be
      associated with history of previous stroke.

PMID- 23954882
TI  - Cloning and expression of cDNA encoding lysyl hydroxylase 1, 2 and 3 in tiger
      puffer Takifugu rubripes.
AB  - Lysyl hydroxylase (LH) catalyzes the hydroxylation of lysine residues in
      collagens, and contributes to the formation of more stable collagen cross-links.
      However, in teleost, there is little information about collagen modification
      enzymes including lysyl oxidase (LOX) family members. Here, we cloned cDNAs
      encoding LH1, 2 and 3 from tiger puffer Takifugu rubripes. To determine the mRNA
      expressions of LH family members in a tiger puffer, we performed a northern blot
      analysis. Results showed that both fgLH1 and fgLH3 mRNAs were almost
      constitutively expressed in tissues, but highly expressed in muscle and ovary,
      respectively. However, fgLH2 mRNA was detected only in RT-PCR, indicating that
      expression level of fgLH2 is very low in tissues. It may be that low expression
      level of fgLH2 contributes to the fewer contents of stable collagen cross-links
      in tiger puffer tissues. To further investigate expression profiles of fgLHs, we
      examined gene expressions in embryos during development. In embryos, expression
      profiles differ among three fgLHs, indicating that there are functional
      differences among the three fgLHs. This is the first report that examined gene
      expression patterns of three LHs in emrbyos and adult tissues in teleost. 

PMID- 23954884
TI  - Rebuilding MTOCs upon centriole loss during mouse oogenesis.
AB  - The vast majority of animal cells contain canonical centrosomes as a main
      microtubule-organizing center defined by a central pair of centrioles. As a rare
      and striking exception to this rule, vertebrate oocytes loose their centrioles at
      an early step of oogenesis. At the end of oogenesis, centrosomes are eventually
      replaced by numerous acentriolar microtubule-organizing centers (MTOCs) that
      shape the spindle poles during meiotic divisions. The mechanisms involved in
      centrosome and acentriolar MTOCs metabolism in oocytes have not been elucidated
      yet. In addition, little is known about microtubule organization and its impact
      on intracellular architecture during the oocyte growth phase following centrosome
      disassembly. We have investigated this question in the mouse by coupling
      immunofluorescence and live-imaging approaches. We show that growing oocytes
      contain dispersed pericentriolar material, responsible for microtubule assembly
      and distribution all over the cell. The gradual enlargement of PCM foci
      eventually leads in competent oocytes to the formation of big perinuclear MTOCs
      and to the assembly of large microtubule asters emanating from the close vicinity
      of the nucleus. Upon meiosis resumption, perinuclear MTOCs spread around the
      nuclear envelope, which in parallel is remodelled before breaking-down, via a MT-
      and dynein-dependent mechanism. Only fully competent oocytes are able to perform
      this dramatic reorganization at NEBD. Therefore, the MTOC-MT reorganization that
      we describe is one of key feature of mouse oocyte competency.

PMID- 23954883
TI  - Cross-linking of CD81 by HCV-E2 protein inhibits human intrahepatic plasmacytoid
      dendritic cells response to CpG-ODN.
AB  - Plasmacytoid dendritic cells (pDCs) are reported to be defective in HCV-infected
      patients, the mechanisms of which remain poorly understood. We isolated liver
      derived mononuclear cells (LMNCs) and pDCs from normal liver tissues of benign
      tumor dissections and liver transplant donors. Isolated pDCs and LMNCs were
      cultured with precoated HCV envelop protein E2 (HCV-E2) or anti-CD81 mAb in the
      presence of CpG-ODN. Our results show that cross-linking of CD81 by either HCV-E2
      or anti-CD81 mAb inhibits IFN-alpha secretion in CpG-induced pDCs; down-regulates
      HLA-DR, CD80 and CD86 expression in pDCs; and suppresses CpG-ODN induced
      proliferation and survival of pDCs. The blockade of CD81 by soluble anti-CD81
      antibody restores pDCs response to CpG-ODN. These results suggest that HCV E2
      protein interacts with CD81 to inhibit pDC maturation, activation, and IFN-alpha
      production, and may thereby contribute to the impaired innate anti-viral immune
      response in HCV infection. 

PMID- 23954885
TI  - Exploring the public health potential of a mass community participation event.
AB  - BACKGROUND: The role of mass participation sports events in encouraging regular
      physical activity is under-researched. This study explored the public health
      potential of parkrun, a UK-wide network of free weekly timed 5-km runs in public
      parks. METHODS: A total of 7308 adult participants of parkrun self-reported
      demographic characteristics, current physical activity and the perceived impact
      of involvement. Objective data on attendance and 5-km performance were available
      from the central parkrun database. RESULTS: At registration 25.3% of participants
      described themselves as non-runners, with this group including the highest
      proportions of females (53.8 versus 48.9% for the total sample), overweight/obese
      (45.2 versus 33.2%) and those with a limiting disability (6.1 versus 4.3%). The
      initial non-runners had the largest increase in 5-km performance (15.8 versus
      10.2%), and were more likely to report health-related benefits. More regular
      attendance was positively associated with perceived benefits. Middle-aged and
      older adults were well represented overall (60.9 and 14.3% of the sample,
      respectively). CONCLUSIONS: Preliminary evidence suggests that parkrun is
      attractive to non-runners, with women, older adults and overweight people well
      represented. The observed fitness improvements and perceived benefits indicate
      the scope for investigating the effectiveness of parkrun as a cost-effective
      community-based intervention for improving public health.

PMID- 23954886
TI  - Trends in recognition and treatment of dementia in france analysis of the 2004 to
      2010 database of the national health insurance plan.
AB  - Dementia is considered as underdiagnosed. We examined whether the proportion of
      persons aged 65 years and older who had been diagnosed as demented has changed
      over a 7-year period. The study population was constituted by a cohort of about
      70,000 persons who were representative of the French elderly covered by the
      national health care insurance plan. Data about all health care consumptions were
      extracted from the national insurance database. Patients using an antidementia
      drug, having a special dementia-related coverage status, or both were identified.
      Annual age-standardized and sex-standardized proportions of recognized dementia
      cases were estimated. Between 2004 and 2010, the overall standardized proportion
      of persons recognized as having dementia increased slightly but significantly
      (P<0.004) from 3.68% to 4.20%. The proportion of persons recognized as demented
      increased strongly with age. In 2010, it increased from 1.44% at age 70-74 to 10%
      at age more than 90 in men and from 1.30% to 17.0% in women. The proportion of
      cholinesterase inhibitor users decreased after the age of 85 years, whereas
      memantine use continued to increase. Our study suggested that, in 2010, >75% of
      the demented persons had been recognized and received pharmacological or/and
      nonpharmacological therapies for dementia. 

PMID- 23954887
TI  - Dysexecutive versus amnestic Alzheimer disease subgroups: analysis of
      demographic, genetic, and vascular factors.
AB  - The objective of this study was to compare the demographic and vascular
      characteristics and APOE genotypes of a dysexecutive subgroup of Alzheimer
      disease (AD) with an amnestic subgroup of AD early in the disease course. A total
      of 2224 participants from the National Alzheimer's Coordinating Center database
      who carried a diagnosis of mild cognitive impairment (n=1188) or mild AD
      (clinical dementia rating <=1) (n=1036) were included in this study. A subset of
      the mild cognitive impairment (n=61) and mild AD (n=79) participants underwent an
      autopsy. A dysexecutive subgroup (n=587) was defined as having executive
      performance >1 SD worse than memory performance, and an amnestic subgroup (n=549)
      was defined conversely. Among the autopsy subset, the odds of an AD pathologic
      diagnosis were compared in the 2 subgroups. The demographics, APOE[Latin Small
      Letter Open E]4 status, and vascular risk factors were compared in the 2
      subgroups. Among the autopsy subset, the odds of having an AD pathologic
      diagnosis did not differ between the dysexecutive and amnestic subgroups. Under
      an additive model, participants in the dysexecutive subgroup possessed the
      APOE[Latin Small Letter Open E]4 allele less frequently compared with those in
      the amnestic subgroup. The dysexecutive subgroup had a history of hypertension
      less frequently compared with the amnestic subgroup. These distinct
      characteristics add to accumulating evidence that a dysexecutive subgroup of AD
      may have a unique underlying pathophysiology. 

PMID- 23954889
TI  - Pomalidomide, cyclophosphamide, and prednisone for relapsed/refractory multiple
      myeloma: a multicenter phase 1/2 open-label study.
AB  - We performed a phase 1/2 trial to determine the maximum tolerated dose (MTD) of
      pomalidomide and to explore its efficacy when combined with cyclophosphamide
      prednisone in relapsed/refractory myeloma patients. Pomalidomide was given at 1
      to 2.5 mg/d, cyclophosphamide at 50 mg every other day, prednisone at 50 mg every
      other day, for 6 28-day cycles, followed by pomalidomide-prednisone maintenance
      therapy. Thromboprophylaxis was recommended. Sixty-nine patients were enrolled,
      55 received the MTD (2.5 mg/d) and were evaluated. Best responses included
      complete response in 3 patients (5%), very good partial response in 10 (18%),
      partial response in 15 (27%), minimal response in 11 (20%), stable disease in 15
      (27%), and progressive disease in 1 (3%), for an overall response rate of 51%.
      The median time-to-response was 1.83 months. After a median follow-up of 14.8
      months, median progression-free survival was 10.4 months and 1-year overall
      survival was 69%. At the MTD, grade 3 to 4 toxicities included anemia (9%),
      thrombocytopenia (11%), neutropenia (42%), neurologic events (7%), dermatologic
      events (7%), and thromboembolism (2%). Grade 3 to 5 infections occurred in 5
      patients (9%). Five patients (9%) discontinued treatment for toxicity. New grade
      3 to 4 adverse events were low during maintenance. Pomalidomide-cyclophosphamide
      prednisone is safe and effective in relapsed/refractory myeloma patients. This
      trial was registered at www.clinicaltrials.gov as #NCT01166113. 

PMID- 23954890
TI  - The biology and clinical impact of genetic lesions in myeloid malignancies.
AB  - A longstanding endeavor to define the genetic lesions that drive myeloid
      malignances has stimulated a period of remarkable discovery. Enabled by
      technological advances that have sharply decreased the cost of DNA sequencing,
      the full compendium of common, recurrent somatic mutations in the coding genome
      of myeloid malignancies is nearly complete. As the focus of genetic discovery
      shifts to the noncoding genome, renewed attention is being applied to the
      clinical and biological implications of recent genomic advances. Although the
      potential for this newfound knowledge to influence the care of patients has not
      yet been realized, broad genetic surveys of patient samples are now being used to
      improve the accuracy of disease diagnosis, define a molecular taxonomy of myeloid
      malignancies, refine prognostic and predictive models, and identify novel
      therapeutic strategies. Here, we will review recent advances in the genetics of
      myeloid malignancies and discuss their potential impact on clinical practice. 

PMID- 23954891
TI  - Ovariectomy expands murine short-term hemopoietic stem cell function through T
      cell expressed CD40L and Wnt10B.
AB  - Estrogen deficiency expands hemopoietic stem and progenitor cells (HSPCs) and
      mature blood lineages, but the involved mechanism and the affected HSPC
      populations are mostly unknown. Here we show that ovariectomy (ovx) expands short
      term HSPCs (ST-HSPCs) and improves blood cell engraftment and host survival after
      bone marrow (BM) transplantation through a dual role of the T-cell costimulatory
      molecule CD40 ligand (CD40L). This surface receptor is required for ovx to
      stimulate T-cell production of Wnt10b, a Wnt ligand that activates Wnt signaling
      in HSPCs and stromal cells (SCs). Moreover, CD40L is required for ovx to increase
      SC production of the hemopoietic cytokines interleukin (IL)-6, IL-7, and
      granulocyte macrophage-colony-stimulating factor. Attesting to the relevance of
      CD40L and Wnt10b, ovx fails to expand ST-HSPCs in CD40L-null mice and in animals
      lacking global or T-cell expression of Wnt10b. In summary, T cells expressed
      CD40L, and the resulting increased production of Wnt10b and hemopoietic cytokines
      by T cells and SCs, respectively, plays a pivotal role in the mechanism by which
      ovx regulates hemopoiesis. The data suggest that antiestrogens may represent
      pharmacological targets to improve ST-HSPC function through activation of the
      microenvironment. 

PMID- 23954892
TI  - Anti-beta2GPI antibodies stimulate endothelial cell microparticle release via a
      nonmuscle myosin II motor protein-dependent pathway.
AB  - The antiphospholipid syndrome is characterized by thrombosis and recurrent fetal
      loss in patients with antiphospholipid antibodies (APLAs). Most pathogenic APLAs
      are directed against beta2-glycoprotein I (beta2GPI), a plasma phospholipid
      binding protein. One mechanism by which circulating antiphospholipid/anti
      beta2GPI antibodies may promote thrombosis is by inducing the release of
      procoagulant microparticles from endothelial cells. However, there is no
      information available concerning the mechanisms by which anti-beta2GPI antibodies
      induce microparticle release. In seeking to identify proteins phosphorylated
      during anti-beta2GPI antibody-induced endothelial activation, we observed
      phosphorylation of nonmuscle myosin II regulatory light chain (RLC), which
      regulates cytoskeletal assembly. In parallel, we observed a dramatic increase in
      the formation of filamentous actin, a two- to fivefold increase in the release of
      endothelial cell microparticles, and a 10- to 15-fold increase in the expression
      of E-selectin, intercellular adhesion molecule 1, vascular cell adhesion molecule
      1, and tissue factor messenger RNA. Microparticle release, but not endothelial
      cell surface E-selectin expression, was blocked by inhibiting RLC phosphorylation
      or nonmuscle myosin II motor activity. These results suggest that distinct
      pathways, some of which mediate cytoskeletal assembly, regulate the endothelial
      cell response to anti-beta2GPI antibodies. Inhibition of nonmuscle myosin II
      activation may provide a novel approach for inhibiting microparticle release by
      endothelial cells in response to anti-beta2GPI antibodies. 

PMID- 23954893
TI  - Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in
      human AML.
AB  - Mutations in the metabolic enzymes isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2)
      are frequently found in glioma, acute myeloid leukemia (AML), melanoma, thyroid
      cancer, and chondrosarcoma patients. Mutant IDH produces 2-hydroxyglutarate
      (2HG), which induces histone- and DNA-hypermethylation through inhibition of
      epigenetic regulators. We investigated the role of mutant IDH1 using the mouse
      transplantation assay. Mutant IDH1 alone did not transform hematopoietic cells
      during 5 months of observation. However, mutant IDH1 greatly accelerated onset of
      myeloproliferative disease-like myeloid leukemia in mice in cooperation with
      HoxA9 with a mean latency of 83 days compared with cells expressing HoxA9 and
      wild-type IDH1 or a control vector (167 and 210 days, respectively, P = .001).
      Mutant IDH1 accelerated cell-cycle transition through repression of cyclin
      dependent kinase inhibitors Cdkn2a and Cdkn2b, and activated mitogen-activated
      protein kinase signaling. By computational screening, we identified an inhibitor
      of mutant IDH1, which inhibited mutant IDH1 cells and lowered 2HG levels in
      vitro, and efficiently blocked colony formation of AML cells from IDH1-mutated
      patients but not of normal CD34(+) bone marrow cells. These data demonstrate that
      mutant IDH1 has oncogenic activity in vivo and suggest that it is a promising
      therapeutic target in human AML cells. 

PMID- 23954894
TI  - Identification in CLL of circulating intraclonal subgroups with varying B-cell
      receptor expression and function.
AB  - Chronic lymphocytic leukemia (CLL) is a tumor of circulating B cells, variably
      stimulated and anergized following exposure to antigen in lymphoid tissues. Down
      modulation of surface IgM (sIgM) occurs, but expression and signal capacity can
      recover in vitro and apparently in vivo during recirculation. We have now
      dissected individual circulating clones of CLL cases according to sIgM expression
      level by differential binding to bead-bound anti-IgM. Four clear subgroups (SG1
      4) with increasing sIgM were identified in 37/37 cases. Engagement of sIgM
      induced phosphorylation of PLCgamma2 and ERK1/2 at levels ranging from very low
      in SG1 to high in SG4. Phosphorylation was suppressed by the BTK inhibitor
      ibrutinib. Expression of CXCR4 also increased from SG1 to SG4, but markers of
      previous activation and proliferation were dominant in SG1. Incubation of whole
      CLL populations in vitro led to striking increases in CXCR4 expression as well as
      recovery of sIgM. Clonal analysis reveals dynamic SGs following presumed antigen
      stimulation in tissues. SG4 represents a fully recovered, potentially dangerous
      population equipped to migrate to tissue and receive a proliferative stimulus.
      SG1 likely represents a postmitotic unresponsive "resting" population. The effect
      of ibrutinib on the small SG4 population may be the critical factor in
      therapeutic success. 

PMID- 23954896
TI  - G protein-coupled receptors: a double attack on pain.

PMID- 23954897
TI  - Regulatory evaluation of Glybera in Europe - two committees, one mission.

PMID- 23954895
TI  - Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond.
AB  - The bioactive lipid sphingosine-1-phosphate (S1P) is involved in multiple
      cellular signalling systems and has a pivotal role in the control of immune cell
      trafficking. As such, S1P has been implicated in disorders such as cancer and
      inflammatory diseases. This Review discusses the ways in which S1P might be
      therapeutically targeted - for example, via the development of chemical
      inhibitors that target the generation, transport and degradation of S1P and via
      the development of specific S1P receptor agonists. We also highlight recent
      conflicting results observed in preclinical studies targeting S1P and discuss
      ongoing clinical trials in this field.

PMID- 23954898
TI  - Neurodegenerative disorders: Linking apolipoprotein E to LOAD.

PMID- 23954899
TI  - Cancer: Special delivery service.

PMID- 23954900
TI  - A prospective study evaluating the clinical relevance of a chemoresponse assay
      for treatment of patients with persistent or recurrent ovarian cancer.
AB  - OBJECTIVE: Use of in vitro chemoresponse assays for informing effective treatment
      selection is a compelling clinical question and a topic of debate among
      oncologists. A prospective study was conducted evaluating the use of a
      chemoresponse assay in recurrent ovarian cancer patients. METHODS: Women with
      persistent or recurrent ovarian cancer were enrolled under an IRB-approved
      protocol, and fresh tissue samples were collected for chemoresponse testing.
      Patients were treated with one of 15 protocol-designated treatments empirically
      selected by the oncologist, blinded to the assay results. Each treatment was
      classified by the assay as: sensitive (S), intermediate (I), or resistant (R).
      Patients were prospectively monitored for progression-free survival (PFS) and
      overall survival (OS). Associations of assay response for the physician-selected
      treatment with PFS and OS were analyzed. RESULTS: A total of 262 evaluable
      patients were enrolled. Patients treated with an assay-sensitive regimen
      demonstrated significantly improved PFS and OS while there was no difference in
      clinical outcomes between I and R groups. Median PFS was 8.8 months for S vs. 5.9
      months for I+R (hazard ratio [HR]=0.67, p=0.009). The association with assay
      response was consistent in both platinum-sensitive and platinum-resistant tumors
      (HR: 0.71 vs. 0.66) and was independent of other covariates in multivariate
      analysis (HR=0.66, p=0.020). A statistically significant14-month improvement in
      mean OS (37.5 months for S vs. 23.9 months for I+R, HR=0.61, p=0.010) was
      demonstrated. CONCLUSIONS: This prospective study demonstrated improved PFS and
      OS for patients with either platinum-sensitive or platinum-resistant recurrent
      ovarian cancer treated with assay-sensitive agents.

PMID- 23954901
TI  - Surgical practice of UK gynaecological oncologists in the treatment of primary
      advanced epithelial ovarian cancer (PAEOC): a questionnaire survey.
AB  - OBJECTIVE: To assess the routine surgical practices of consultant gynaecological
      oncologists (CGOs) in the United Kingdom in their management of primary advanced
      (FIGO stages III and IV) epithelial ovarian cancer (PAEOC). METHODS: The same
      anonymised questionnaire was sent twice to all consultant gynaecological
      oncologists (CGOs) working in the UK. The questions enquired about surgical
      practice of the previous calendar year and the respondents were asked to describe
      their usual or typical management of patients with PAEOC. RESULTS: 45 of 85 CGOs
      responded (53%). The mean number of ovarian cancer cases operated on by an
      individual surgeon was 47 (range 6-100). 6% of the surgeons never perform pelvic
      lymphadenectomy, and 22% of the surgeons never perform para-aortic
      lymphadenectomy in the primary surgery (PS) group, compared to 8% and 30% in the
      neoadjuvant chemotherapy (NAC) group. In the PS group 17% of the respondents
      perform pelvic lymphadenectomy routinely (80% or more of patients) compared to
      11% of the respondents in the NAC group. The rates of bowel surgery and surgery
      for upper abdominal disease were highly variable. The average operating time per
      case was less than 3h in 78% of the respondents. CONCLUSIONS: The mean operating
      times, caseload, and types of procedure undertaken in the management of advanced
      ovarian cancer provide compelling evidence that in many UK cancer centres the
      surgical goal has not been complete cytoreduction. These data have implications
      for the centralisation of surgical services, subspecialty training, and the lower
      survival of UK patients compared to other comparable countries.

PMID- 23954902
TI  - Predictive value of circulating tumor cells (CTCs) in newly-diagnosed and
      recurrent ovarian cancer patients.
AB  - OBJECTIVE: To determine whether circulating tumor cells (CTCs), as detected and
      enumerated by the Veridex CellSearch system, could predict for clinical outcomes
      in women with newly diagnosed or recurrent epithelial ovarian cancer. METHODS:
      Serial measurements of CTC s and paired serum CA125 were collected in a series of
      78 women with newly diagnosed or recurrent ovarian cancer seen at our institution
      over a period of 15 months. Clinical data were abstracted from patient medical
      records. CTCs were detected and enumerated by the CellSearch protocol, and
      patients were divided into CTC negative (<2 CTCs) or positive (>=2 CTCs) groups.
      CTC groups were correlated with clinical characteristics and outcomes. A
      longitudinal analysis of CTC change and CA125 trends was also performed. RESULTS:
      At least one CTC was isolated from the peripheral blood of over 80% of the women
      participating in this study, with a range from 0 to 8. No correlations were
      observed between CTC numbers and clinical characteristics or outcomes. Although
      both serum CA125 and CTC number exhibited an overall significant decreasing trend
      over time, there was no correlation observed between change in CTCs and CA125.
      CONCLUSION: Using the FDA-approved CellSearch system, CTCs can be isolated from
      women with newly diagnosed or recurrent ovarian cancer. However, CTC numbers do
      not significantly correlate with clinical characteristics or patient outcomes.
      Future studies should focus on phenotypic characterization of CTCs and whether
      different isolation protocols yield a higher number of CTCs or add prognostic
      value.

PMID- 23954903
TI  - Use of complex surgical procedures, patterns of tumor spread, and CA-125 predicts
      a risk of incomplete cytoreduction: a Korean Gynecologic Oncology Group study
      (KGOG-3022).
AB  - OBJECTIVES: We aimed to develop a risk model to predict a risk of suboptimal
      cytoreduction in primary surgery of ovarian cancer. METHODS: The clinical records
      and computed tomography (CT) data of 358 patients with stages II-IV epithelial
      ovarian cancer were reviewed. Tumor spread patterns identified by principal
      component analysis, CA-125, and a newly developed surgical skill index were
      integrated into a logistic model along with other variables. Internal validation
      was performed using bootstrapped re-sampling and calibration was assessed by
      goodness-of-fit test. RESULTS: Among the 358 patients, optimal cytoreduction,
      which was defined as no residual tumor, was achieved in 145 patients (40.5%). The
      surgical capacity of an individual institution was estimated by a surgical skill
      index, which was the frequency of complex surgeries in patients with advanced
      disease. In a multivariate model, two distinctive CT patterns of tumor spread
      (diffuse spread pattern and upper abdominal extension pattern), a surgical skill
      index, and serum CA-125 independently predicted a risk of suboptimal
      cytoreduction (P=0.006, P=0.013, P=0.031, and P=0.001, respectively). The model
      showed a C-statistic of .73 (95% confidence interval .67 to .79), which was
      significantly higher than tumor stage or ascites. Rigorous internal validation by
      bootstrapped re-sampling successfully confirmed the model. CONCLUSIONS: We
      identified two distinct tumor spread patterns of ovarian cancer, which can be
      integrated to improve a prediction model. Our model may be useful in patient
      referral or clinical trials for patient stratification.

PMID- 23954905
TI  - [Ulcerating tumor in the duodenum and head of the pancreas].

PMID- 23954907
TI  - Optimal M-estimation in high-dimensional regression.
AB  - We consider, in the modern setting of high-dimensional statistics, the classic
      problem of optimizing the objective function in regression using M-estimates when
      the error distribution is assumed to be known. We propose an algorithm to compute
      this optimal objective function that takes into account the dimensionality of the
      problem. Although optimality is achieved under assumptions on the design matrix
      that will not always be satisfied, our analysis reveals generally interesting
      families of dimension-dependent objective functions. 

PMID- 23954906
TI  - [Challenges in building a surgical obesity center].
AB  - BACKGROUND: It is estimated that approximately 1 million adults in Germany suffer
      from grade III obesity. The aim of this article is to describe the challenges
      faced when constructing an operative obesity center. METHODS: The inflow of
      patients as well as personnel and infrastructure of the interdisciplinary
      Diabetes and Obesity Center in Heidelberg were analyzed. The distribution of
      continuous data was described by mean values and standard deviation and analyzed
      using variance analysis. RESULTS: The interdisciplinary Diabetes and Obesity
      Center in Heidelberg was founded in 2006 and offers conservative therapeutic
      treatment and all currently available operative procedures. For every operative
      intervention carried out an average of 1.7 expert reports and 0.3 counter
      expertises were necessary. The time period from the initial presentation of
      patients in the department of surgery to an operation was on average 12.8 months
      (standard deviation SD +/- 4.5 months). The 47 patients for whom remuneration for
      treatment was initially refused had an average body mass index (BMI) of 49.2
      kg/m(2) and of these 39 had at least the necessity for treatment of a
      comorbidity. Of the 45 patients for whom the reason for the refusal of treatment
      costs was given as a lack of conservative treatment, 30 had undertaken a
      medically supervised attempt at losing weight over at least 6 months.
      Additionally, 19 of these patients could document participation in a course at a
      rehabilitation center, a Xenical(r) or Reduktil(r) therapy or had undertaken the
      Optifast(r) program. For the 20 patients who supposedly lacked a psychosomatic
      evaluation, an adequate psychosomatic evaluation was carried out in all cases.
      CONCLUSIONS: The establishment of an operative obesity center can last for
      several years. A essential prerequisite for success seems to be the constructive
      and targeted cooperation with the health insurance companies.

PMID- 23954908
TI  - On robust regression with high-dimensional predictors.
AB  - We study regression M-estimates in the setting where p, the number of covariates,
      and n, the number of observations, are both large, but p <= n. We find an exact
      stochastic representation for the distribution of beta = argmin(beta?R(p))
      Sigma(i=1)(n) rho(Y(i) - X(i')beta) at fixed p and n under various assumptions on
      the objective function rho and our statistical model. A scalar random variable
      whose deterministic limit rrho(kappa) can be studied when p/n -> kappa > 0 plays
      a central role in this representation. We discover a nonlinear system of two
      deterministic equations that characterizes rrho(kappa). Interestingly, the system
      shows that rrho(kappa) depends on rho through proximal mappings of rho as well as
      various aspects of the statistical model underlying our study. Several surprising
      results emerge. In particular, we show that, when p/n is large enough, least
      squares becomes preferable to least absolute deviations for double-exponential
      errors.

PMID- 23954909
TI  - QnAs with Carol S. Dweck. Interview by Sujata Gupta.

PMID- 23954910
TI  - Improving resuscitation quality.

PMID- 23954911
TI  - Co-administration of 5-HT6 receptor antagonists with clozapine, risperidone, and
      a 5-HT2A receptor antagonist: effects on prepulse inhibition in rats.
AB  - RATIONALE: Some novel antipsychotics manifest antagonistic activity at serotonin
      6 receptors; however, little is known about the role of 5-HT6 receptors in
      ameliorating sensory gating deficits. OBJECTIVE: We evaluated the effects of the
      combined administration of the 5-HT6 receptor antagonist SB 271046 with clozapine
      and haloperidol, as well as the co-administration of SB 271046 or SB 399885 with
      risperidone and the 5-HT2A antagonist M100907, to overcome the deficits induced
      by MK-801 in the prepulse inhibition (PPI) test. RESULTS: MK-801 (0.1 mg/kg)
      produced reliable PPI deficits. Administration of SB 271046 (6 and 9 mg/kg), SB
      399885 (3 and 6 mg/kg), clozapine (2.5 mg/kg), haloperidol (0.1 and 0.2 mg/kg),
      risperidone (0.25-1 mg/kg), and M100907 (0.5 and 1 mg/kg) did not affect the MK
      801-induced deficits, but the administration of clozapine (5 mg/kg) did reverse
      the effects of MK-801. In MK-801-treated rats, the co-administration of inactive
      doses of clozapine (2.5 mg/kg) and SB 271046 (6 mg/kg) reversed the PPI
      impairments compared to animals that were administered inactive doses of either
      clozapine or SB 271046 alone. Co-administration of risperidone (1 mg/kg) or
      M100907 (0.5 mg/kg) with SB 271046 (6 mg/kg) or SB 399885 (3 mg/kg) also
      attenuated the MK-801-induced PPI deficits. In contrast, joint administration of
      haloperidol and SB 271046 had no effect on the PPI deficit. CONCLUSION: The
      present results suggest that the 5-HT6 receptors may play adjunctive roles in
      antipsychotic drug action, and that the combination of 5-HT2A and 5-HT6
      antagonism may represent an important element in the pharmacological profile of
      antipsychotic drugs.

PMID- 23954913
TI  - Spatially varying determinants of farmland conversion across Qiantang watershed,
      China.
AB  - This paper employed geographically weighted regression (GWR) to characterize the
      determinants of farmland conversion at administrative scale between 1994 and 2003
      across Qiantang watershed, China. Six determinants were identified: total area of
      forest, distance to highway, distance to second road, distance to river,
      population, and gross domestic product. Relationships between these identified
      determinants and farmland conversion showed great spatial non-stationarity, since
      their character, nature, and strength varied significantly across space.
      Typically, for cities whose development was heavily relied on road infrastructure
      development, the impacts of "distance to second road" and "distance to river" was
      negative. However, in mountainous areas, the restriction of terrain factors led
      to positive impacts from these two variables. For areas undergoing rapid socio
      economic development, farmland conversion was accelerated by population growth
      and economic development. However, for more urbanized regions, a slow-down rate
      of farmland conversion would be expected. Our study highlighted that the problem
      of spatial non-stationarity should be addressed when qualifying the determinants
      of farmland conversion. Linking our results within the context of farmland
      protection, we argue that implementing local-specific land management practices,
      instead of the current one-size-fits-all framework, is the key for the success of
      farmland protection in China. 

PMID- 23954912
TI  - Neural correlates of free T3 alteration after catecholamine depletion in subjects
      with remitted major depressive disorder and in controls.
AB  - RATIONALE: Thyroid hormones and their interactions with catecholamines play a
      potentially important role in alterations of mood and cognition. OBJECTIVES: This
      study aimed to examine the neurobiological effects of catecholamine depletion on
      thyroid hormones by measuring endocrine and cerebral metabolic function in
      unmedicated subjects with remitted major depressive disorder (RMDD) and in
      healthy controls. METHODS: This was a randomized, placebo-controlled, and double
      blind crossover trial that included 15 unmedicated RMDD subjects and 13 healthy
      control subjects. The participants underwent two 3-day-long sessions at 1-week
      intervals; each participant was randomly administered oral alpha-methyl-para
      tyrosine in one session (catecholamine depletion) and an identical capsule
      containing hydrous lactose (sham depletion) in the other session prior to a
      [(18)F]-fluorodeoxyglucose positron emission tomography scan. RESULTS: Serum
      concentrations of free T3 (FT3), free T4 (FT4), and TSH were obtained and
      assessed with respect to their relationship to regional cerebral glucose
      metabolism. Both serum FT3 (P = 0.002) and FT4 (P = 0.0009) levels were less
      suppressed after catecholamine depletion compared with placebo treatment in the
      entire study sample. There was a positive association between both FT3 (P =
      0.0005) and FT4 (P = 0.002) and depressive symptoms measured using the Montgomery
      Asberg Depression Rating Scale. The relative elevation in FT3 level was
      correlated with a decrease in regional glucose metabolism in the right
      dorsolateral prefrontal cortex (rDLPFC; P < 0.05, corrected). CONCLUSIONS: This
      study provided evidence of an association between a thyroid-catecholamine
      interaction and mood regulation in the rDLPFC.

PMID- 23954914
TI  - Are small-scale irrigators water use efficient? Evidence from lake Naivasha
      basin, Kenya.
AB  - With increasing water scarcity and competing uses and users, water use efficiency
      is becoming increasingly important in many parts of developing countries. The
      lake Naivasha basin has an array of different water users and uses ranging from
      large scale export market agriculture, urban domestic water users to small holder
      farmers. The small scale farmers are located in the upper catchment areas and
      form the bulk of the users in terms of area and population. This study used farm
      household data to explore the overall technical efficiency, irrigation water use
      efficiency and establish the factors influencing water use efficiency among small
      scale farmers in the Lake Naivasha basin in Kenya. Data envelopment analysis,
      general algebraic and modeling system, and Tobit regression methods were used in
      analyzing cross sectional data from a sample of 201 small scale irrigation
      farmers in the lake Naivasha basin. The results showed that on average, the
      farmers achieved only 63 % technical efficiency and 31 % water use efficiency.
      This revealed that substantial inefficiencies occurred in farming operations
      among the sampled farmers. To improve water use efficiency, the study recommends
      that more emphasis be put on orienting farmers toward appropriate choice of
      irrigation technologies, appropriate choice of crop combinations in their farms,
      and the attainment of desirable levels of farm fragmentation. 

PMID- 23954915
TI  - Environmental flows can reduce the encroachment of terrestrial vegetation into
      river channels: a systematic literature review.
AB  - Encroachment of riparian vegetation into regulated river channels exerts control
      over fluvial processes, channel morphology, and aquatic ecology. Reducing
      encroachment of terrestrial vegetation is an oft-cited objective of environmental
      flow recommendations, but there has been no systematic assessment of the evidence
      for and against the widely-accepted cause-and-effect mechanisms involved. We
      systematically reviewed the literature to test whether environmental flows can
      reduce the encroachment of terrestrial vegetation into river channels. We
      quantified the level of support for five explicit cause-effect hypotheses drawn
      from a conceptual model of the effects of flow on vegetation. We found that
      greater inundation, variously expressed as changes in the area, depth, duration,
      frequency, seasonality, and volume of surface water, generally reduces riparian
      vegetation abundance in channels, but most studies did not investigate the
      specific mechanisms causing these changes. Those that did show that increased
      inundation results in increased mortality, but also increased germination. The
      evidence was insufficient to determine whether increased inundation decreases
      reproduction. Our results contribute to hydro-ecological understanding by using
      the published literature to test for general cause-effect relationships between
      flow regime and terrestrial vegetation encroachment. Reviews of this nature
      provide robust support for flow management, and are more defensible than expert
      judgement-based approaches. Overall, we predict that restoration of more natural
      flow regimes will reduce encroachment of terrestrial vegetation into regulated
      river channels, partly through increased mortality. Conversely, infrequent
      deliveries of environmental flows may actually increase germination and
      subsequent encroachment. 

PMID- 23954916
TI  - Bone morphogenetic protein signaling in nephron progenitor cells.
AB  - Bone morphogenetic protein (BMP) signaling plays an essential role in many
      aspects of kidney development, and is a major determinant of outcome in kidney
      injury. BMP treatment is also an essential component of protocols for
      differentiation of nephron progenitors from pluripotent stem cells. This review
      discusses the role of BMP signaling to nephron progenitor cells in each of these
      contexts. 

PMID- 23954917
TI  - Safety and efficacy of dabigatran etexilate during catheter ablation of atrial
      fibrillation: a meta-analysis of the literature.
AB  - AIMS: To summarize and analyse the published literature on the efficacy and
      safety of dabigatran for anticoagulation during atrial fibrillation (AF)
      ablation. METHODS AND RESULTS: A comprehensive search of the literature in the
      English language was conducted and 10 studies were identified which compared
      dabigatran therapy with warfarin. Data were extracted and meta-analysed using
      appropriate methodology. There was significant clinical heterogeneity among
      studies concerning study designs and methodologies. Most studies consisted of
      retrospective single-centre observational studies. A total of 3648 patients were
      included of whom 2241 were receiving warfarin and 1407 dabigatran. Only 12
      thrombo-embolic events were reported, 3 during warfarin and 9 during dabigatran
      therapy [odds ratio (OR) 2.38, 95% confidence interval (CI) 0.82-6.85, P = n.s.).
      The pooled rate of major bleeding events was similar for warfarin and for
      dabigatran (OR 1.05, 95% CI 0.62-1.80; P = n.s.). Rates of minor bleeding events
      were also similar between the two treatment groups. CONCLUSION: Dabigatran has
      similar efficacy and safety compared with warfarin when used for periprocedural
      anticoagulation during AF ablation.

PMID- 23954918
TI  - Safety and efficacy of interrupted dabigatran for peri-procedural anticoagulation
      in catheter ablation of atrial fibrillation: a systematic review and meta
      analysis.
AB  - AIMS: To examine the safety (defined as bleeding risk) and efficacy (defined as
      prevention of thromboembolic events) of interrupted dabigatran for peri
      procedural anticoagulation in catheter ablation (CA) of atrial fibrillation (AF)
      in comparison with warfarin. METHODS AND RESULTS: Reviewers independently
      searched literature databases from January 2010 through April 2013 for studies
      comparing the safety and efficacy of dabigatran and warfarin in CA of AF and
      extracted pre-defined data. The Mantel-Haenszel method was used to pool data of
      bleeding and thromboembolism outcomes into random and fixed effect model meta
      analyses, respectively. Odds ratios (ORs), and risk difference (RD) analysis when
      studies reported no events in either arm, were used to generate an overall effect
      estimate of both outcomes. Publication bias and heterogeneity were assessed by
      contour funnel plot and the I(2) test, respectively. Nine citations, including
      3036 patients (1073 dabigatran), met the inclusion criteria. There was no
      significant difference between interrupted dabigatran and warfarin therapy in CA
      of AF in occurrence of bleeding [dabigatran 58 (5.4%), warfarin 103 (5.2%); OR
      0.92 (95% confidence interval (CI) 0.55-1.45); chi(2) = 13.03-P = 0.11; I(2) =
      39%] or thromboembolism [dabigatran 5 (0.4%), warfarin 2 (0.1%); OR 2.15 (95% CI
      0.58-7.98); chi(2) = 2.14, P = 0.54; I(2) = 0%; RD 0.00 (95% CI-0.00 to 0.01);
      chi(2) = 3.37, P = 0.81; I(2) = 0%]. Analysis of pre-defined subgroups (published
      articles vs. abstracts), sensitivity analyses (interrupted warfarin, USA studies,
      and Japanese studies) and fixed effect model analyses showed similar results.
      Heterogeneity was mild in the bleeding outcome analysis and zero in
      thromboembolism. There was no evidence of publication bias in either meta
      analysis. CONCLUSION: Meta-analysis of currently available studies showed no
      significant difference in bleeding and thromboembolism between interrupted
      dabigatran and warfarin therapy in CA of AF. Dabigatran appears to be safe and
      effective for peri-procedural anticoagulation in CA of AF.

PMID- 23954919
TI  - Additional benefit of cryoballoon-based atrial fibrillation ablation beyond
      pulmonary vein isolation: modification of ganglionated plexi.
AB  - AIMS: It has been known that cryoballoon-based pulmonary vein isolation (PVI) is
      an efficacious and a safe therapeutic option to eliminate triggers of atrial
      fibrillation (AF). However, the effect of cryoablation on external modifiers of
      AF-like ganglionated plexi (GP) has never been investigated. In this study, we
      aimed to investigate whether vagal reactions probably due to GP modification
      during cryoablation, are associated with success rates during follow-up. METHODS
      AND RESULTS: A total of 145 patients (age: 54.5 +/- 10.1, 52.4% males and 80.7%
      paroxysmal AF) who were symptomatic despite treatment with >= 1 antiarrhythmic
      drug underwent PVI with cryoballoon. Occurrences of intraprocedural vagal
      reactions were recorded in all patients. Intraprocedural vagal reaction was
      observed in 59 patients (40.7%). Vagal reaction characterized by bradycardia and
      hypotension was more common in patients free of AF recurrence as was the
      requirement of atropine administration or temporary pacing (46.2 vs. 15.4%, P =
      0.004 and 38.7 vs. 7.7%, P = 0.002, respectively). At a median 17 (4-27) months
      follow-up, AF recurrence was observed in 26 (17.9%) patients. Multivariate Cox
      regression analysis showed that non-paroxysmal AF, left atrial diameter, and
      early recurrence significantly increased AF recurrence; however, requirement of
      atropine administration or temporary pacing (hazard ratio: 0.064; 95% confidence
      interval: 0.008-0.48, P = 0.008) decreased AF recurrence. CONCLUSION: Our
      findings indicate that vagal reactions during cryoablation, as a surrogate marker
      of cardiac ANS modification, decrease AF recurrence in a subgroup of patients
      with paroxysmal and persistent AF. This finding may be attributed to the
      concomitant ablation of GP during antral PVI.

PMID- 23954920
TI  - The prognostic impact of pre-implantation hyponatremia on morbidity and mortality
      among patients with left ventricular dysfunction and implantable cardioverter
      defibrillators.
AB  - AIMS: Hyponatremia is commonly observed among patients with left ventricular (LV)
      dysfunction and is a marker for adverse outcomes. We aimed to determine the
      prognostic significance of pre-implant hyponatremia on the outcomes of death,
      acute decompensated heart failure (ADHF) and appropriate implantable cardioverter
      defibrillator (ICD) therapy for ventricular arrhythmias among patients with ICDs.
      METHODS AND RESULTS: The study population consisted of patients with an ejection
      fraction <=40% undergoing ICD implantation (n = 911) for the primary or secondary
      prevention of sudden cardiac death from 1997 to 2007. The predictive value of the
      severity of pre-implantation hyponatremia stratified into mild hyponatremia (n =
      268, sodium 134-136 mmol/L), moderate hyponatremia (n = 105, sodium 131-133
      mmol/L), and severe hyponatremia (n = 31, sodium <=130 mmol/L) on the risk of
      death, ADHF, and appropriate ICD therapy for ventricular arrhythmias as compared
      with patients a normal serum sodium (n = 507, sodium >= 137 mmol/L), was
      calculated using multivariable Cox proportional hazards analyses. During a mean
      follow-up of 775 +/- 750 days as the severity of hyponatremia (from a normal
      sodium to severe hyponatremia) increased an incremental incidence of death (25%
      to 61%, P < 0.001) and ADHF (11% to 26%, P = 0.004) was observed with a reduced
      incidence of ICD therapy for ventricular tachycardia/ventricular fibrillation (37
      29%, P = 0.037). Compared with the normal sodium cohort, patients with severe
      hyponatremia demonstrated an increased risk of death [adjusted hazard ratio (AHR)
      2.69 (95% confidence interval, CI 1.57-4.59), P = 0.004] and ADHF [AHR 2.98 (95%
      CI 1.41-6.30), P = 0.004], with a lower probability of appropriate ICD therapy
      [AHR 0.68 (95% CI 0.27-0.88), P = 0.031]. CONCLUSION: Hyponatremia is commonly
      observed among ICD recipients with LV dysfunction. Patients with an increasing
      severity of hyponatremia are at increased risk of death and HF related morbidity
      with a reduced incidence of appropriate ICD therapy particularly among patients
      with severe hyponatremia.

PMID- 23954921
TI  - A fibre-optic oxygen sensor for monitoring human breathing.
AB  - The development and construction of a tapered-tip fibre-optic fluorescence based
      oxygen sensor is described. The sensor is suitable for fast and real-time
      monitoring of human breathing. The sensitivity and response time of the oxygen
      sensor were evaluated in vitro with a gas pressure chamber system, where oxygen
      partial pressure was rapidly changed between 5 and 15 kPa, and then in vivo in
      five healthy adult participants who synchronized their breathing to a metronome
      set at 10, 20, 30, 40, 50, and 60 breaths min(-1). A Datex Ultima medical gas
      analyser was used to monitor breathing rate as a comparator. The sensor's
      response time in vitro was less than 150 ms, which allows accurate continuous
      measurement of inspired and expired oxygen pressure. Measurements of breathing
      rate by means of our oxygen sensor and of the Datex Ultima were in strong
      agreement. The results demonstrate that the device can reliably resolve breathing
      rates up to 60 breaths min(-1), and that it is a suitable cost-effective
      alternative for monitoring breathing rates and end-tidal oxygen partial pressure
      in the clinical setting. The rapid response time of the sensor may allow its use
      for monitoring rapid breathing rates as occur in children and the newborn. 

PMID- 23954922
TI  - Clinical features and prognostic factors of thrombotic thrombocytopenic purpura
      associated with systemic lupus erythematosus: a literature review of 105 cases
      from 1999 to 2011.
AB  - This study aims to review clinical features, treatments, and prognostic factors
      of thrombotic thrombocytopenic purpura (TTP) associated with systemic lupus
      erythematosus patients (sTTP). The case reports of sTTP published in world
      literature from 1999 to 2011 were collected, and 105 cases were divided into
      death group and survival group. The epidemiologic characteristics, clinical
      manifestations, laboratory examinations, treatments, and prognostic factors were
      analyzed. We found that coexistence of renal and neurological impairments were
      significantly frequent in the death group (100%) than in the survival group
      (56.5%) (P = 0.002). Type IV was predominant in 57.7% of renal pathological
      damage, followed by type V (11.5%), type II (5.8%), and thrombotic
      microangiopathy (TMA) (5.8%). TMA appeared more frequently (50%) in the death
      group than in the survival group (6.25%) (P = 0.042). End-stage renal disease
      occurred in nine cases with type IV in five (55.6%), type TMA in one (11.1%), and
      unspecified in three cases (33.3%). Of 32 cases, 40.6% showed severe ADAMTS13
      deficiency and returned to normal or mildly deficient after remission. The total
      mortality rate of sTTP was 12.4 % and the mortality rate of patients with
      infection (27.3%) was significantly higher than those without infection (8.4%) (P
      = 0.028). Plasma exchange and glucocorticoids were administrated in over 80% of
      cases with 65.7% remission rate, while additional cytotoxics or rituximab was
      mostly used in refractory sTTP and achieved over 90 % of remission rate. Above
      all, coexistence of renal and neurological impairments, infection, and renal
      damage with type IV or TMA might denote a poor prognosis of sTTP.

PMID- 23954923
TI  - High rate of disease remission in moderate rheumatoid arthritis on etanercept
      therapy: data from GISEA, the Italian biologics register.
AB  - The aim of this study was to evaluate the clinical outcomes of etanercept in
      rheumatoid arthritis (RA) patients with moderate or severe disease activity. We
      analyzed data from the Italian biologics register Gruppo Italiano Studio Early
      Arthritides (GISEA) to investigate the rate of disease remission and functional
      improvement, based on the 28-Joint Disease Activity Score (DAS28) and the (Health
      Assessment Questionnaire (HAQ) score in RA patients with moderate or severe
      disease activity beginning etanercept therapy. Disease was defined as severe (H
      RA) with DAS28 >=5.1 and moderate (M-RA) with DAS28 >=3.2 to 5.1 at baseline.
      Patients were considered in remission if DAS28 was <=2.6, and HAQ <=0.5 defined
      normal function. We enrolled 953 RA patients, 320 with M-RA and 633 H-RA. Age and
      disease duration were similar in the two cohorts, but H-RA patients had
      significantly more comorbidities (p < 0.01) and took significantly more disease
      modifying antirheumatic drugs (p < 0.001) than M-RA patients. After 1 year, the
      percentage of patients achieving disease remission and normal function (DAS28
      <=2.6 plus HAQ <=0.5) was higher in M-RA (21.4 %) than in H-RA patients (14.8 %,
      p = 0.007), regardless of the disease duration. Additionally, female gender (p =
      0.006) and H-RA class (p = 0.002) negatively predicted disease remission at 1
      year. However, the drug survival rate did not differ between the two subsets.
      This study confirms that etanercept was effective in the treatment of active RA,
      but best response, in terms of disease remission and normal function ability, was
      greater and easier to attain in M-RA patients. These findings may aid clinicians
      to choose the best strategy to treat RA. 

PMID- 23954924
TI  - Developmental expression of dysbindin in Muller cells of rat retina.
AB  - Dysbindin, the product of the DTNBP1 gene, was identified by yeast two hybrid
      assay as a binding partner of dystrobrevin, a cytosolic component of the
      dystrophin protein complex. Although its functional role has not yet been
      completely elucidated, the finding that dysbindin assembles into the biogenesis
      of lysosome related organelles complex 1 (BLOC-1) suggests that it participates
      in intracellular trafficking and biogenesis of organelles and vesicles. Dysbindin
      is ubiquitous and in brain is expressed primarily in neurons. Variations at the
      dysbindin gene have been associated with increased risk for schizophrenia. As
      anomalies in retinal function have been reported in patients suffering from
      neuropsychiatric disorders, we investigated the expression of dysbindin in the
      retina. Our results show that differentially regulated dysbindin isoforms are
      expressed in rat retina during postnatal maturation. Interestingly, we found that
      dysbindin is mainly localized in Muller cells. The identification of dysbindin in
      glial cells may open new perspectives for a better understanding of the
      functional involvement of this protein in visual alterations associated to
      neuropsychiatric disorders. 

PMID- 23954926
TI  - Electrochemical detection of dopamine based on pre-concentration by graphene
      nanosheets.
AB  - Herein, graphene nanosheets (GNS) were synthesized, by a green and facile method
      based on reduction by glucose, and characterized. Afterwards, a carbon paste
      electrode (CPE) was modified with GNS by casting and drying GNS on top of the CPE
      (CPE/GNS). The behavior of the CPE/GNS towards dopamine (DA) and ascorbic acid
      (AA) was investigated by electrochemical methods and the obtained results showed
      that the CPE/GNS had adsorbed only DA. Based on this behavior, the DA molecules
      were pre-concentrated on top of the CPE/GNS, followed by stripping in DA free
      solution. Subsequent to experimental and instrumental optimization, a calibration
      curve from 2.0 * 10(-6) to 1.0 * 10(-3) M DA, r(2) = 0.99 (+/-0.01), with
      detection limit (DL) = 8.5 * 10(-7) M DA, sensitivity = 15.4 (+/-0.94) MUA, and
      RSD = 6.1 was observed in the presence of 1.0 * 10(-3) M AA. Finally, the
      performance of the CPE/GNS was successfully tested in a pharmaceutical sample.
      This work provides a promising strategy for DA detection in the presence of
      biological interferences, e.g. AA, with high sensitivity and simple
      characteristics. 

PMID- 23954925
TI  - Internal attention to features in visual short-term memory guides object
      learning.
AB  - Attending to objects in the world affects how we perceive and remember them. What
      are the consequences of attending to an object in mind? In particular, how does
      reporting the features of a recently seen object guide visual learning? In three
      experiments, observers were presented with abstract shapes in a particular color,
      orientation, and location. After viewing each object, observers were cued to
      report one feature from visual short-term memory (VSTM). In a subsequent test,
      observers were cued to report features of the same objects from visual long-term
      memory (VLTM). We tested whether reporting a feature from VSTM: (1) enhances VLTM
      for just that feature (practice-benefit hypothesis), (2) enhances VLTM for all
      features (object-based hypothesis), or (3) simultaneously enhances VLTM for that
      feature and suppresses VLTM for unreported features (feature-competition
      hypothesis). The results provided support for the feature-competition hypothesis,
      whereby the representation of an object in VLTM was biased towards features
      reported from VSTM and away from unreported features (Experiment 1). This bias
      could not be explained by the amount of sensory exposure or response learning
      (Experiment 2) and was amplified by the reporting of multiple features
      (Experiment 3). Taken together, these results suggest that selective internal
      attention induces competitive dynamics among features during visual learning,
      flexibly tuning object representations to align with prior mnemonic goals. 

PMID- 23954927
TI  - Redesign of genetically encoded biosensors for monitoring mitochondrial redox
      status in a broad range of model eukaryotes.
AB  - The development of genetically encoded redox biosensors has paved the way toward
      chemically specific, quantitative, dynamic, and compartment-specific redox
      measurements in cells and organisms. In particular, redox-sensitive green
      fluorescent proteins (roGFPs) have attracted major interest as tools to monitor
      biological redox changes in real time and in vivo. Most recently, the engineering
      of a redox relay that combines glutaredoxin (Grx) with roGFP2 as a translational
      fusion (Grx1-roGFP2) led to a biosensor for the glutathione redox potential (EGSH
      ). The expression of this probe in mitochondria is of particular interest as
      mitochondria are the major source of oxidants, and their redox status is closely
      connected to cell fate decisions. While Grx1-roGFP2 can be expressed in mammalian
      mitochondria, it fails to enter mitochondria in various nonmammalian model
      organisms. Here we report that inversion of domain order from Grx1-roGFP2 to
      roGFP2-Grx1 yields a biosensor with perfect mitochondrial targeting while fully
      maintaining its biosensor capabilities. The redesigned probe thus allows
      extending in vivo observations of mitochondrial redox homeostasis to important
      nonmammalian model organisms, particularly plants and insects. 

PMID- 23954928
TI  - Targeting RNA binding proteins involved in neurodegeneration.
AB  - Dysfunctions at the level of RNA processing have recently been shown to play a
      fundamental role in the pathogenesis of many neurodegenerative diseases. Several
      proteins responsible for these dysfunctions (TDP-43, FUS/TLS, and hnRNP A/Bs)
      belong to the nuclear class of heterogeneous ribonucleoproteins (hnRNPs) that
      predominantly function as general regulators of both coding and noncoding RNA
      metabolism. The discovery of the importance of these factors in mediating
      neuronal death has represented a major paradigmatic shift in our understanding of
      neurodegenerative processes. As a result, these discoveries have also opened the
      way toward novel biomolecular screening approaches in our search for therapeutic
      options. One of the major hurdles in this search is represented by the correct
      identification of the most promising targets to be prioritized. These may include
      aberrant aggregation processes, protein-protein interactions, RNA-protein
      interactions, or specific cellular pathways altered by disease. In this review,
      we discuss these four major options together with their various advantages and
      drawbacks. 

PMID- 23954929
TI  - Profiling cholinesterase adduction: a high-throughput prioritization method for
      organophosphate exposure samples.
AB  - A high-throughput prioritization method was developed for use with a validated
      confirmatory method detecting organophosphorus nerve agent exposure by
      immunomagnetic separation high-performance liquid chromatography tandem mass
      spectrometry. A ballistic gradient was incorporated into this analytical method
      to profile unadducted butyrylcholinesterase (BChE) in clinical samples. With
      Zhang et al.'s Z' factor of 0.88 +/- 0.01 (SD) of control analytes and Z factor
      of 0.25 +/- 0.06 (SD) of serum samples, the assay is rated an "excellent assay"
      for the synthetic peptide controls used and a "double assay" when used to
      prioritize clinical samples. Hits, defined as samples containing BChE Ser-198
      adducts or no BChE present, were analyzed in a confirmatory method for
      identification and quantitation of the BChE adduct, if present. The ability to
      prioritize samples by highest exposure for confirmatory analysis is of particular
      importance in an exposure to cholinesterase inhibitors such as organophosphorus
      nerve agents, in which a large number of clinical samples may be collected. In an
      initial blind screen, 67 of 70 samples were accurately identified, giving an
      assay accuracy of 96%, and it yielded no false-negatives. The method is the first
      to provide a high-throughput prioritization assay for profiling adduction of Ser
      198 BChE in clinical samples. 

PMID- 23954930
TI  - A novel organelle map framework for high-content cell morphology analysis in high
      throughput.
AB  - A screening procedure was developed that takes advantage of the cellular
      normalization by micropatterning and a novel quantitative organelle mapping
      approach that allows unbiased and automated cell morphology comparison using
      black-box statistical testing. Micropatterns of extracellular matrix proteins
      force cells to adopt a reproducible shape and distribution of intracellular
      compartments avoiding strong cell-to-cell variation that is a major limitation of
      classical culture conditions. To detect changes in cell morphology induced by
      compound treatment, fluorescently labeled intracellular structures from several
      tens of micropatterned cells were transformed into probabilistic density maps.
      Then, the similarity or difference between two given density maps was quantified
      using statistical testing that evaluates differences directly from the data
      without additional analysis or any subjective decision. The versatility of this
      organelle mapping approach for different magnifications and its performance for
      different cell shapes has been assessed. Density-based analysis detected changes
      in cell morphology due to compound treatment in a small-scale proof-of-principle
      screen demonstrating its compatibility with high-throughput screening. This novel
      tool for high-content and high-throughput cellular phenotyping can potentially be
      used for a wide range of applications from drug screening to careful
      characterization of cellular processes. 

PMID- 23954931
TI  - An isogenic cell panel identifies compounds that inhibit proliferation of mTOR
      pathway addicted cells by different mechanisms.
AB  - The mTOR pathway is a critical integrator of nutrient and growth factor
      signaling. Once activated, mTOR promotes cell growth and proliferation. Several
      components of the mTOR pathway are frequently deregulated in tumors, leading to
      constitutive activation of the pathway and thus contribute to uncontrolled cell
      growth. We performed a high-throughput screen with an isogenic cell line system
      to identify compounds specifically inhibiting proliferation of PTEN/mTOR-pathway
      addicted cells. We show here the characterization and mode of action of two such
      compound classes. One compound class inhibits components of the PTEN/mTOR
      signaling pathway, such as S6 ribosomal protein phosphorylation, and leads to
      cyclin D3 downregulation. These compounds are not adenosine triphosphate
      competitive inhibitors for kinases in the pathway, nor do they require FKBP12 for
      activity like rapamycin. The other compound class turned out to be a
      farnesylation inhibitor, blocking the activity of GTPases, as well as an inducer
      of oxidative stress. Our results demonstrate that an isogenic cell system with
      few specific mutations in oncogenes and tumor suppressor genes can identify
      different classes of compounds selectively inhibiting proliferation of PTEN/mTOR
      pathway-addicted isogenic clones. The identified mechanisms are in line with the
      known cellular signaling networks activated by the altered oncogenes and
      suppressor genes in the isogenic system. 

PMID- 23954932
TI  - Transforming TRP channel drug discovery using medium-throughput
      electrophysiological assays.
AB  - Since the cloning of its first member in 1998, transient receptor potential (TRP)
      cation channels have become one of the most studied ion channel families in drug
      discovery. These channels, almost all calcium permeant, have been studied in many
      different (patho)-physiological and therapeutic areas as diverse as pain;
      neurodegenerative, cardiovascular, and inflammatory diseases; and cancer. At the
      same time, implementation of automated electrophysiology screening platforms has
      significantly increased the tractability of ion channels, mainly voltage gated,
      as drug targets. The work presented in this article shows the design and
      validation of TRP screening assays using the IonWorks Quattro platform (Molecular
      Devices, Sunnyvale, CA), allowing a significant increase in throughput to support
      drug discovery programs. This new player has a direct impact on resources and
      timelines by prioritizing potential candidates and reducing the number of
      molecules requiring final testing by manual patch-clamp, which is still today the
      gold standard technology for this challenging drug target class. 

PMID- 23954933
TI  - Methane as raw material in synthetic chemistry: the final frontier.
AB  - In spite of its large availability in natural or shale gas deposits, the use of
      methane in the chemical industry as feedstock from a synthetic point of view yet
      constitutes a challenge in modern chemistry. Only the production of the so-called
      syngas, a mixture of CO and H2 derived from the complete cleavage of the methane
      molecule, operates at the industrial level. The relevance of methane in the
      current industry, mainly toward methanol production, is described in this
      Tutorial. The methanol economy has been already proposed as an alternative to
      current fuel sources. Methanol synthesis directly from methane would imply the
      activation of the latter. Toward this end, the different methodologies reported
      to activate methane with transition metal complexes as well as the few examples
      of the catalytic functionalization of methane are presented. 

PMID- 23954934
TI  - Photoelectrochemical lab-on-paper device equipped with a porous Au-paper
      electrode and fluidic delay-switch for sensitive detection of DNA hybridization.
AB  - The sequence-specific detection of DNA hybridization has attracted considerable
      interest in numerous fields. Although traditional DNA biosensors have been widely
      explored due to their high sensitivity, it is still challenging to develop a low
      cost, portable, disposable, fast, and easy-to-use DNA detection method for public
      use at home or in the field. To address these challenges, herein, we report a
      novel microfluidic photoelectrochemical (PEC) paper-based analytical platform,
      integrated with an internal chemiluminescent light source, a novel paper
      supercapacitor (PS) amplifier, and a terminal digital multi-meter (DMM) detector,
      for sensitive DNA detection using a graphene-modified porous Au-paper electrode
      as the working electrode to obtain enhanced PEC responses. The quantification
      mechanism of this strategy is based on the charging of this PS, which was
      constructed on a paper-based analytical platform through a simple "drawing and
      soaking" method, by the generated photocurrent. After a fixed period, the PS was
      automatically shorted under the control of a novel built-in fluidic delay-switch
      to output an instantaneously amplified current, which could be sensitively
      detected by the DMM. At optimal conditions, this paper-based analytical platform
      can detect DNA at concentrations at femtomolar level. This approach also shows
      excellent specificity toward single nucleotide mismatches. 

PMID- 23954935
TI  - Biodegradation of 4-bromophenol by Arthrobacter chlorophenolicus A6 in batch
      shake flasks and in a continuously operated packed bed reactor.
AB  - The present study investigated growth and biodegradation of 4-bromophenol (4-BP)
      by Arthrobacter chlorophenolicus A6 in batch shake flasks as well as in a
      continuously operated packed bed reactor (PBR). Batch growth kinetics of A.
      chlorophenolicus A6 in presence of 4-BP followed substrate inhibition kinetics
      with the estimated biokinetic parameters value of MU max = 0.246 h(-1), K i = 111
      mg L(-1), K s  = 30.77 mg L(-1) and K = 100 mg L(-1). In addition, variations in
      the observed and theoretical biomass yield coefficient and maintenance energy of
      the culture were investigated at different initial 4-BP concentration. Results
      indicates that the toxicity tolerance and the biomass yield of A.
      chlorophenolicus A6 towards 4-BP was found to be poor as the organism utilized
      the substrate mainly for its metabolic maintenance energy. Further, 4-BP
      biodegradation performance by the microorganism was evaluated in a continuously
      operated PBR by varying the influent concentration and hydraulic retention time
      in the ranges 400-1,200 mg L(-1) and 24-7.5 h, respectively. Complete removal of
      4-BP was achieved in the PBR up to a loading rate of 2,276 mg L(-1) day(-1). 

PMID- 23954937
TI  - Antiviral immunity: A 'mature' way of controlling HBV.

PMID- 23954938
TI  - Efficacy of a self-management intervention for weight control in overweight and
      obese adults: a randomized controlled trial.
AB  - Brief self-management interventions to engender successful weight maintenance are
      seldom tested in obese and overweight populations without diabetes. To test the
      efficacy of the intervention, aimed at improving proactive coping, in obese and
      overweight adults at risk for diabetes. Participants (N = 255) were randomly
      assigned to two experimental groups (N = 185) and a control group (N = 70).
      Experimental groups received the same intervention in week 1-8 (initial phase)
      and booster sessions with different content ("standard" vs. "relapse prevention")
      during week 9-24 (continuance phase). Primary outcomes were proactive coping,
      diet and Body Mass Index (BMI) at four time points (1 year between first and last
      measurement). Experimental groups improved in proactive coping during the initial
      phase and BMI during the continuance phase, whereas the control group did not. No
      differences emerged in diet. Brief self-management interventions can play a
      preventive role in chronic illnesses associated with obesity. 

PMID- 23954936
TI  - Mitogen-activated protein kinases in innate immunity.
AB  - Following pathogen infection or tissue damage, the stimulation of pattern
      recognition receptors on the cell surface and in the cytoplasm of innate immune
      cells activates members of each of the major mitogen-activated protein kinase
      (MAPK) subfamilies--the extracellular signal-regulated kinase (ERK), p38 and Jun
      N-terminal kinase (JNK) subfamilies. In conjunction with the activation of
      nuclear factor-kappaB and interferon-regulatory factor transcription factors,
      MAPK activation induces the expression of multiple genes that together regulate
      the inflammatory response. In this Review, we discuss our current knowledge about
      the regulation and the function of MAPKs in innate immunity, as well as the
      importance of negative feedback loops in limiting MAPK activity to prevent host
      tissue damage. We also examine how pathogens have evolved complex mechanisms to
      manipulate MAPK activation to increase their virulence. Finally, we consider the
      potential of the pharmacological targeting of MAPK pathways to treat autoimmune
      and inflammatory diseases.

PMID- 23954939
TI  - Immunization to prevent congenital cytomegalovirus infection.
AB  - INTRODUCTION: A primary maternal cytomegalovirus (CMV) during pregnancy causes
      newborn disease that includes hearing deficit and/or mental retardation. SOURCES
      OF DATA: Relevant published literature. AREAS OF AGREEMENT: There are no biologic
      obstacles to immunization against fetal/placental infection with CMV. AREAS OF
      UNCERTAINTY: CMV vaccine trials may be difficult due to a lack of public
      awareness of CMV. Vaccine trials that use fetal infection as an endpoint will be
      prolonged, since vaccination will need to occur preconception. AREAS TIMELY FOR
      DEVELOPING RESEARCH: Vaccines in preclinical development include antigens of the
      CMV gB glycoprotein and the gH/gL UL128, 130 and 131 pentameric complex. These
      antigens induce antibodies that block viral entry into fibroblasts and
      endothelial/epithelial cells. Vaccines immunogenic in animals include an
      inactivated virus with a wild-type UL131 gene, a DNA vaccine using a wild-type
      UL130 gene and peptide vaccines using peptides from UL130 and 131. CONCLUSIONS:
      In spite of these potential obstacles, successful evaluation of CMV vaccines is
      possible.

PMID- 23954940
TI  - Design of a universal biointerface for sensitive, selective, and multiplex
      detection of biomarkers using surface plasmon resonance imaging.
AB  - This paper reports on the sensitive, selective, and simultaneous detection of
      four protein biomarkers involved in metastasis of various cancers, namely Fas,
      angiopoietin-2 (Ang-2), human epidermal growth factor receptor 2 (HER2), and
      matrix metallopeptidase-9 (MMP-9) using an antibody-conjugated quantum dot (QD)
      chip and surface plasmon resonance imaging (SPRi) biosensors. Initially, a self
      assembled monolayer film of l-cysteine, using glutaraldehyde as a linker and QDs
      as signal enhancement moieties, was employed to immobilize anti-Fas for the
      detection of Fas as a model protein in buffer. The biointerface was characterized
      using confocal microscopy, atomic force microscopy, and scanning electron
      microscopy to provide evidence of uniform surface coverage by the QDs. The SPRi
      signal was enhanced 100-fold to achieve a detection limit of 25 pg mL(-1) after
      applying biotinylated detection antibody-conjugate streptavidin-modified QDs.
      Secondly, this signal amplification strategy was applied to sequentially detect
      Fas, HER2, MMP-9, and Ang-2 at low concentrations on a protein-microprinted/gold
      coated SPRi chip. The results showed the absence of cross-reactivity among these
      proteins and the feasibility of the approach for multiplex detection of
      biomarkers as required for the accurate diagnosis of various diseases. 

PMID- 23954941
TI  - Detection and elimination profile of cathinone in equine after norephedrine
      (Propalin(r)) administration using a validated liquid chromatography-tandem mass
      spectrometry method.
AB  - Cathinone is the principal psychostimulant present in the leaves of khat shrub,
      which are widely used in East Africa and the Arab peninsula as an amphetamine
      like stimulant. Cathinone readily undergoes metabolism in vivo to form less
      potent cathine and norephedrine as the metabolites. However, the presence of
      cathine and norephedrine in biological fluids cannot be used as an indicator of
      cathinone administration. The metabolism of pseudoephedrine and ephedrine,
      commonly used in cold and allergy medications, also produces cathine and
      norephedrine, respectively, as the metabolites. Besides, cathine and norephedrine
      may also originate from the ingestion of nutritional supplemental products
      containing extracts of Ephedra species. In Canada, ephedrine and norephedrine are
      available for veterinary use, whereas cathinone is not approved for human or
      veterinary use. In this article, the detection of cathinone in equine after
      administration of norephedrine is reported. To the best of our knowledge, this is
      the first such report in any species where administration of norephedrine or
      ephedrine generates cathinone as the metabolite. This observation is quite
      significant, because in equine detection of cathinone in biological fluids could
      be due to administration of the potent stimulant cathinone or the nonpotent
      stimulant norephedrine. A single oral dose of 450 mg norephedrine was
      administered to four Standardbred mares. Plasma and urine samples were collected
      up to 120 h after administration. The amount of cathinone and norephedrine
      detected in post administration samples was quantified using a highly sensitive,
      specific, and validated liquid chromatography-tandem mass spectrometry method.
      Using these results, we constructed elimination profiles for cathinone and
      norephedrine in equine plasma and urine. A mechanism that generates a geminal
      diol as an intermediate is postulated for this in vivo conversion of norephedrine
      to cathinone. Cathinone was also detected in samples collected after a single
      intramuscular administration of 200 mg ephedrine and oral administration of 300
      mg ephedrine in equine.

PMID- 23954943
TI  - Studies on drug metabolism by fungi colonizing decomposing human cadavers. Part
      I: DNA sequence-based identification of fungi isolated from postmortem material.
AB  - Cadavers can be colonized by a wide variety of bacteria and fungi. Some of these
      microbes could change the concentration or the metabolic pattern of drugs present
      in postmortem samples. The purpose of this study was to identify fungi from human
      postmortem material and to further assess their potential role in the metabolism
      of drugs. Aliquots of 252 postmortem samples (heart blood, liver, kidney, and
      lung) taken from 105 moderately to severely decomposed bodies were streaked on
      Sabouraud agar for isolation of fungal species. One part of the samples was
      worked up immediately after autopsy (group I). The second part had previously
      been stored at -20  degrees C for at least 1 year (group II). Identification of
      the isolates was achieved morphologically by microscopy and molecularly by
      polymerase chain reaction amplification and sequencing of markers allowing
      species identification of the respective genera. Depending on the genus,
      different gene fragments were used: calmodulin for Aspergillus, beta-tubulin for
      Penicillium, translation elongation factor 1alpha for Fusarium, and the internal
      transcribed spacer region of the ribosomal DNA for all remaining genera. A total
      of 156 fungal strains were isolated from 62% of the postmortem materials. By
      using these primers, 98% of the isolates could be identified to the species
      level. The most common genera were Candida (60.0%-six species), Penicillium
      (10.3%-two species), Rhodotorula (7.1%-one species), Mucor (6.4%-four species),
      Aspergillus (3.2%-four species), Trichosporon (3.2%-one species), and Geotrichum
      (3.2%-one species). Group I samples contained 53% more fungal species than stored
      samples suggesting some fungi did not survive the freezing process. The isolated
      fungi might be characteristic for decomposed bodies. The proposed methodology
      proved to be appropriate for the identification of fungi in this type of
      material.

PMID- 23954942
TI  - A portable gas chromatograph with simultaneous detection by mass spectrometry and
      electroantennography for the highly sensitive in situ measurement of volatiles.
AB  - Mating disruption is a sustainable method for the control of insect pests,
      involving the release of synthetic sex pheromones that disrupt the olfactory
      localization of females by males. However, the development and refinement of this
      strategy is hampered because current instruments lack the sensitivity to detect
      volatile organic chemicals in the field, and portable electroantennograms produce
      non-comparable relative units and distorted results in the presence of plant
      volatiles. To address the demand for more sensitive instruments that are suitable
      for the rapid in situ detection of airborne pheromones, we have developed a
      portable, automated needle trap device connected to a gas chromatograph, mass
      spectrometer, and electroantennographic detector (NTD-GC-MS/EAD) suitable for
      field applications. We tested the instrument by measuring the concentration of
      the sex pheromone (E,Z)-7,9-dodecadienyl acetate, which is used to disrupt the
      mating of the European grapevine moth Lobesia botrana (Lepidoptera: Tortricidae).
      Our data confirm that the instrument generates highly reproducible results and is
      highly sensitive, with a detection threshold of 3 ng/m(3) (E,Z)-7,9-dodecadienyl
      acetate in outside air. 

PMID- 23954944
TI  - Oral fluid cannabinoid concentrations following controlled smoked cannabis in
      chronic frequent and occasional smokers.
AB  - Oral fluid (OF) is an alternative biological matrix for monitoring cannabis
      intake in drug testing, and drugged driving (DUID) programs, but OF cannabinoid
      test interpretation is challenging. Controlled cannabinoid administration studies
      provide a scientific database for interpreting cannabinoid OF tests. We compared
      differences in OF cannabinoid concentrations from 19 h before to 30 h after
      smoking a 6.8% THC cigarette in chronic frequent and occasional cannabis smokers.
      OF was collected with the Statsure Saliva SamplerTM OF device. 2D-GC-MS was used
      to quantify cannabinoids in 357 OF specimens; 65 had inadequate OF volume within
      3 h after smoking. All OF specimens were THC-positive for up to 13.5 h after
      smoking, without significant differences between frequent and occasional smokers
      over 30 h. Cannabidiol (CBD) and cannabinol (CBN) had short median last detection
      times (2.5-4 h for CBD and 6-8 h for CBN) in both groups. THCCOOH was detected in
      25 and 212 occasional and frequent smokers' OF samples, respectively. THCCOOH
      provided longer detection windows than THC in all frequent smokers. As THCCOOH is
      not present in cannabis smoke, its presence in OF minimizes the potential for
      false positive results from passive environmental smoke exposure, and can
      identify oral THC ingestion, while OF THC cannot. THC >= 1 MUg/L, in addition to
      CBD >= 1 MUg/L or CBN >= 1 MUg/L suggested recent cannabis intake (<=13.5 h),
      important for DUID cases, whereas THC >= 1 MUg/L or THC >= 2 MUg/L cutoffs had
      longer detection windows (>=30 h), important for workplace testing. THCCOOH
      windows of detection for chronic, frequent cannabis smokers extended beyond 30 h,
      while they were shorter (0-24 h) for occasional cannabis smokers.

PMID- 23954945
TI  - Empirical derived AUD sub types in the US general population: a latent class
      analysis.
AB  - AIMS: This study examined the homogenous expression of DSM-5-based alcohol use
      disorder (AUD) latent subtypes. METHOD: Using data from the National
      Epidemiologic Survey of Alcohol and Related Conditions Wave 2 (n = 22,177) the
      typology was established utilising latent class analysis and the model was
      further validated by multivariate regression on a range of covariates. RESULTS:
      Three AUD classes based on a severity gradient and one non-problematic class were
      the most parsimonious description of the data. These classes displayed both
      quantitative and qualitative differences on the covariates. CONCLUSIONS: The
      resulting typology has high clinical utility, enhances AUD classification and
      adds to our understanding of AUD trajectories, prevention and treatment.

PMID- 23954946
TI  - Behavioural therapy for smoking cessation: the effectiveness of different
      intervention types for disadvantaged and affluent smokers.
AB  - BACKGROUND: Disadvantaged smokers are less likely to be successful when trying to
      stop smoking than more affluent smokers. In the UK, NHS Stop Smoking Services
      (SSS) provide a range of pharmacotherapy and behavioural support, delivered by
      advisors with a range of backgrounds. Whether the types of support provided and
      who provides it influence differences in quit rates amongst low SES smokers
      compared with high SES smokers has not previously been examined. METHODS: 202,084
      records of smokers in England who attended a NHS Stop Smoking Service between
      July 2010 and June 2011 were acquired. Smokers were followed-up by services at
      four weeks post quit date. Multilevel logistic regression models of CO validated
      quits were employed. Disadvantage was explored through the National Statistics
      Socio-Economic Classification (NS-SEC) and by eligibility for free prescriptions,
      an indicator of low income amongst adults aged between 19 and 59 in England.
      RESULTS: Affluent smokers were more likely to quit than disadvantaged smokers (OR
      1.38 (1.35 to 1.42) for clients who paid for prescriptions compared to those
      eligible for free prescriptions). 80% of service clients received one-to-one
      counselling but open group forms of behavioural therapy were more successful
      (main effect OR 1.26 (1.12 to 1.41)) except amongst some of the most
      disadvantaged clients (long-term unemployed and prisoners). Closed groups were
      little deployed and they were not significantly more successful than one-to-one
      behavioural therapy after controls. Who delivered treatment did make a difference
      for some clients, with all but the most affluent less likely to be successful if
      they had been treated by a nurse compared with other types of advisers, including
      smoking cessation specialists (main effect OR 0.73 (0.65 to 0.83)). CONCLUSION:
      This study provides further evidence that disadvantaged smokers find quitting
      more difficult even when they have attended a smoking cessation programme. The
      findings suggest that open groups should be promoted, although they may not be as
      effective as other forms of behavioural therapy for the long-term unemployed or
      prisoners. Further research is required to explore why most groups of smokers who
      attended services staffed by nurses were less likely to quit than those who
      received treatment from other types of advisors.

PMID- 23954948
TI  - Full screening and accurate subtyping of HLA-A*02 alleles through group-specific
      amplification and mono-allelic sequencing.
AB  - HLA-A*02 is the most prevalent and polymorphic major histocompatibility complex
      (MHC) allele family in humans. Functional differences have been revealed among
      subtypes, demanding further subtyping of HLA-A*02 in basic and clinical settings.
      However, the fast growing polymorphisms render traditional primer- or probe-based
      typing methods impractical and result in increasing ambiguities in direct
      sequence-based typing. In this study, we combined group-specific amplification
      and mono-allelic sequencing to design and validate a simple scheme for the
      complete screening and accurate subtyping of all 540 reported HLA-A*02 alleles.
      This scheme could be performed in routine labs to facilitate studies with an
      interest in HLA-A*02. 

PMID- 23954949
TI  - The shrimp IKK-NF-kappaB signaling pathway regulates antimicrobial peptide
      expression and may be subverted by white spot syndrome virus to facilitate viral
      gene expression.
AB  - The IkappaB kinases IKKalpha and IKKbeta and the IKK-related kinases TANK-binding
      kinase 1 (TBK1) and IKKepsilon are the master regulators of the NF-kappaB
      signaling pathway. Although this pathway has been extensively studied in mammals,
      less attention has been paid in crustaceans, which have significant economic
      value. Here, we report the cloning and functional studies of two IKK homologs,
      LvIKKbeta and LvIKKepsilon, from Pacific white shrimp, Litopenaeus vannamei.
      LvIKKbeta and LvIKKepsilon mRNAs are widely expressed in different tissues and
      are responsive to white spot syndrome virus (WSSV) infection. When overexpressed
      in Drosophila S2 cells, LvIKKbeta but not LvIKKepsilon activates the promoters of
      NF-kappaB pathway-controlled antimicrobial peptide genes (AMPs), such as the
      Penaeidins (PENs). In HEK 293T cells, both LvIKKbeta and LvIKKepsilon activate an
      NF-kappaB reporter. The silencing of LvIKKbeta or LvIKKepsilon using double
      stranded RNA (dsRNA)-mediated RNA interference (RNAi) decreases the expression of
      L. vannamei AMPs, including PENs, lysozyme and crustins. Intriguingly, LvIKKbeta-
      or LvIKKepsilon-silenced L. vannamei are resistant to WSSV infection. We
      hypothesized that successful infection with WSSV requires the activation of the
      IKK-NF-kappaB signaling pathway to modulate viral gene expression. We constructed
      luciferase reporters for 147 WSSV genes. By screening, we found that the WSV051,
      WSV059, WSV069, WSV083, WSV090, WSV107, WSV244, WSV303, WSV371 and WSV445
      promoters can be activated by LvIKKbeta or LvIKKepsilon in Drosophila S2 cells.
      Taken together, our results reveal that LvIKKbeta and LvIKKepsilon may
      participate in the regulation of shrimp AMPs and that WSSV may subvert the L.
      vannamei IKK-NF-kappaB signaling pathway to facilitate viral gene expression. 

PMID- 23954947
TI  - The role of chemokines in acute and chronic hepatitis C infection.
AB  - Hepatitis C imposes a significant burden on global healthcare. Chronic infection
      is associated with progressive inflammation of the liver which typically
      manifests in cirrhosis, organ failure and cancer. By virtue of elaborate evasion
      strategies, hepatitis C virus (HCV) succeeds as a persistent human virus. It has
      an extraordinary capacity to subvert the immune response enabling it to establish
      chronic infections and associated liver disease. Chemokines are low molecular
      weight chemotactic peptides that mediate the recruitment of inflammatory cells
      into tissues and back into the lymphatics and peripheral blood. Thus, they are
      central to the temporal and spatial distribution of effector and regulatory
      immune cells. The interactions between chemokines and their cognate receptors
      help shape the immune response and therefore, have a major influence on the
      outcome of infection. However, chemokines represent a target for modulation by
      viruses including the HCV. HCV is known to modulate chemokine expression in vitro
      and may therefore enable its survival by subverting the immune response in vivo
      through altered leukocyte chemotaxis resulting in impaired viral clearance and
      the establishment of chronic low-grade inflammation. In this review, the roles of
      chemokines in acute and chronic HCV infection are described with a particular
      emphasis placed on chemokine modulation as a means of immune subversion. We
      provide an in depth discussion of the part played by chemokines in mediating
      hepatic fibrosis while addressing the potential applications for these
      chemoattractants in prognostic medicine. 

PMID- 23954951
TI  - Evolution of photosystem I and the control of global enthalpy in an oxidizing
      world.
AB  - Life on earth is governed by light, chemical reactions, and the second law of
      thermodynamics, which defines the tendency for increasing entropy as an
      expression of disorder or randomness. Life is an expression of increasing order,
      and a constant influx of energy and loss of entropic wastes are required to
      maintain or increase order in living organisms. Most of the energy for life comes
      from sunlight and, thus, photosynthesis underlies the survival of all life forms.
      Oxygenic photosynthesis determines not only the global amount of enthalpy in
      living systems, but also the composition of the Earth's atmosphere and surface.
      Photosynthesis was established on the Earth more than 3.5 billion years ago. The
      primordial reaction center has been suggested to comprise a homodimeric unit
      resembling the core complex of the current reaction centers in Chlorobi,
      Heliobacteria, and Acidobacteria. Here, an evolutionary scenario based on the
      known structures of the current reaction centers is proposed. 

PMID- 23954950
TI  - Thrombospondin 1 activates the macrophage Toll-like receptor 4 pathway.
AB  - Previously, we demonstrated that macrophages from thrombospondin 1 (TSP1)
      deficient mice have a reduced inflammatory phenotype, suggesting that TSP1 plays
      a role in macrophage activation. In this study, we determined how TSP1 regulates
      macrophage function. We found that recombinant or purified platelet human TSP1
      treatment stimulated tumor-necrosis factor (TNF)-alpha expression in bone marrow
      derived macrophages in a time- and dose-dependent manner. Toll-like receptor 4
      (TLR4) expression (at the mRNA and protein levels) and nuclear factor-kappaB (NF
      kappaB) activity were also stimulated by TSP1 treatment. The TSP1-mediated
      increase in TNF-alpha production was abolished in TLR4-deficient macrophages,
      suggesting that TSP1 activates macrophages through a TLR4-dependent pathway. TSP1
      also stimulated TLR4 activation in macrophages in vivo. Furthermore, TSP1
      mediated macrophage activation was attenuated by using a peptide or an antibody
      to block the association between TSP1 and CD36. Taken together, these data
      suggest that the stimulation of the macrophage TLR4 pathway by TSP1 is partially
      mediated by the interaction of TSP1 with its receptor, CD36. 

PMID- 23954952
TI  - Metabolic flux analysis of Cyanothece sp. ATCC 51142 under mixotrophic
      conditions.
AB  - Cyanobacteria are a group of photosynthetic prokaryotes capable of utilizing
      solar energy to fix atmospheric carbon dioxide to biomass. Despite several "proof
      of principle" studies, low product yield is an impediment in commercialization of
      cyanobacteria-derived biofuels. Estimation of intracellular reaction rates by
      (13)C metabolic flux analysis ((13)C-MFA) would be a step toward enhancing
      biofuel yield via metabolic engineering. We report (13)C-MFA for Cyanothece sp.
      ATCC 51142, a unicellular nitrogen-fixing cyanobacterium, known for enhanced
      hydrogen yield under mixotrophic conditions. Rates of reactions in the central
      carbon metabolism under nitrogen-fixing and -non-fixing conditions were estimated
      by monitoring the competitive incorporation of (12)C and (13)C from unlabeled CO2
      and uniformly labeled glycerol, respectively, into terminal metabolites such as
      amino acids. The observed labeling patterns suggest mixotrophic growth under both
      the conditions, with a larger fraction of unlabeled carbon in nitrate-sufficient
      cultures asserting a greater contribution of carbon fixation by photosynthesis
      and an anaplerotic pathway. Indeed, flux analysis complements the higher growth
      observed under nitrate-sufficient conditions. On the other hand, the flux through
      the oxidative pentose phosphate pathway and tricarboxylic acid cycle was greater
      in nitrate-deficient conditions, possibly to supply the precursors and reducing
      equivalents needed for nitrogen fixation. In addition, an enhanced flux through
      fructose-6-phosphate phosphoketolase possibly suggests the organism's preferred
      mode under nitrogen-fixing conditions. The (13)C-MFA results complement the
      reported predictions by flux balance analysis and provide quantitative insight
      into the organism's distinct metabolic features under nitrogen-fixing and -non
      fixing conditions. 

PMID- 23954953
TI  - Clear castable polyurethane elastomer for fabrication of microfluidic devices.
AB  - Polydimethylsiloxane (PDMS) has numerous desirable properties for fabricating
      microfluidic devices, including optical transparency, flexibility,
      biocompatibility, and fabrication by casting; however, partitioning of small
      hydrophobic molecules into the bulk of PDMS hinders industrial acceptance of PDMS
      microfluidic devices for chemical processing and drug development applications.
      Here we describe an attractive alternative material that is similar to PDMS in
      terms of optical transparency, flexibility and castability, but that is also
      resistant to absorption of small hydrophobic molecules. 

PMID- 23954954
TI  - Early social deprivation negatively affects social skill acquisition in
      chimpanzees (Pan troglodytes).
AB  - In a highly social species like chimpanzees, the process by which individuals
      become attuned to their social environment may be of vital importance to their
      chances of survival. Typically, this socialization process, defined by all
      acquisition experiences and fine-tuning efforts of social interaction patterns
      during ontogeny, occurs in large part through parental investment. In this study,
      we investigated whether maternal presence enhances the socialization process in
      chimpanzees by comparing the social interactions of orphaned and mother-reared
      individuals at the Chimfunshi Wildlife Orphanage Trust in Zambia. As response
      variables, we selected social interactions during which an elaborate level of
      fine-tuning is assumed to be necessary for sustaining the interaction and
      preventing escalation: social play. Comparing orphaned (n = 8) to sex- and age
      matched mother-reared juvenile chimpanzees (n = 9), we hypothesized that the
      orphaned juveniles would play less frequently than the mother-reared and would be
      less equipped for fine-tuning social play (which we assayed by rates of
      aggression) because of the lack of a safe and facilitating social environment
      provided by the mother. First, contrary to our hypothesis, results showed that
      the orphaned juveniles engaged in social play more frequently than the mother
      reared juveniles, although for significantly shorter amounts of time. Second, in
      support of our hypothesis, results showed that social play of the orphaned
      juveniles more often resulted in aggression than social play of the mother-reared
      juveniles. In conjunction, these results may indicate that, just like in humans,
      chimpanzee mothers provide their offspring with adequate social skills that might
      be of pivotal importance for future challenges like successful group-living and
      securing competitive fitness advantages. 

PMID- 23954955
TI  - Metallic anodes for next generation secondary batteries.
AB  - Li-air(O2) and Li-S batteries have gained much attention recently and most
      relevant research has aimed to improve the electrochemical performance of air(O2)
      or sulfur cathode materials. However, many technical problems associated with the
      Li metal anode have yet to be overcome. This review mainly focuses on the
      electrochemical behaviors and technical issues related to metallic Li anode
      materials as well as other metallic anode materials such as alkali (Na) and
      alkaline earth (Mg) metals, including Zn and Al when these metal anodes were
      employed for various types of secondary batteries. 

PMID- 23954956
TI  - [Guidelines for the diagnosis and treatment of Helicobacter pylori infection in
      Korea, 2013 revised edition].
AB  - Since the Korean College of Helicobacter and Upper Gastrointestinal Research has
      first developed the guideline for the diagnosis and treatment of Helicobacter
      pylori infection in 1998, the revised guideline was proposed in 2009 by the same
      group. Although the revised guideline was made by comprehensive review of
      previous articles and consensus of authoritative expert opinions, the evidence
      based developmental process was not applied in the revision of the guideline.
      This new guideline has been revised especially in terms of changes in the
      indication and treatment of H. pylori infection in Korea, and developed by the
      adaptation process as evidence-based method; 6 guidelines were retrieved by
      systematic review and the Appraisal of Guidelines for Research and Evaluation
      (AGREE) II process, 21 statements were made with grading system and revised by
      modified Delphi method. After revision, 11 statements for the indication of test
      and treatment, 4 statements for the diagnosis and 4 statements for the treatment
      have been developed, respectively. The revised guideline has been reviewed by
      external experts before the official endorsement, and will be disseminated for
      usual clinical practice in Korea. Also, the scheduled update and revision of the
      guideline will be made periodically.

PMID- 23954957
TI  - [Clinicopathologic features of colorectal cancer combined with synchronous and
      metachronous gastric cancer].
AB  - BACKGROUND/AIMS: The purpose of this study was to investigate the
      clinicopathologic features of double primary cancers of the stomach and
      colorectum, compared to colorectal cancer alone. METHODS: A retrospective
      analysis was made of 5,288 patients who underwent colorectal cancer surgery
      between January 2000 and December 2009 at Severance Hospital of Yonsei
      University. The clinicopathologic features were analyzed between 63 patients of
      double primary cancers and case-matched 126 patients of colorectal cancer alone.
      We classified double primary cancers into subgroups as premetachronous,
      synchronous and postmetachronous gastric cancer to identify differences between
      the three subgroups also. RESULTS: Double primary cancers group showed 4.3 year
      older age, lower BMI, and higher percentage of peritoneal metastasis, compared to
      colorectal cancer alone group. Overall and colorectal cancer specific survival
      did not have any significant difference between two groups. In histologic type of
      gastric cancer, a high percentage of undifferentiated adenocarcinoma (55.6%) and
      signet ring cell carcinoma (30.2%) were noted. CONCLUSIONS: Double primary
      cancers of the stomach and colorectum had older-age onset, lower BMI and higher
      metastasis to peritoneum than colorectal cancer alone. Combined gastric cancer
      consisted of high percentage of undifferentiated and signet ring cell carcinomas.

PMID- 23954959
TI  - [The incidence and clinical characteristics of proximal colonic polyps when the
      polyps are noted on rectosigmoid colon by colonoscopy].
AB  - BACKGROUND/AIMS: Colorectal cancer is the third most common type of cancer and
      second leading cause of cancer death overall. Recently, there has been an
      emphasis on primary screening for colorectal cancer with colonoscopy. In this
      study, we aimed to address clinical characteristics and incidence of colonic
      polyps according to location. METHODS: From January 2009 to December 2010, 6,417
      total colonoscopic examinations were performed at Boramae Hospital in Seoul,
      Korea. We reviewed these patients retrospectively. The distal colon was defined
      as the rectosigmoid junction. RESULTS: Overall, 1,972 patients (31.3%) had one of
      more colorectal polyps. Total of 4,445 patients were excluded from this study
      because of combined advanced colorectal cancer, inflammatory bowel disease, or
      familial adenomatous polyposis. Patients who had only proximal polyps were 633
      (32.1%), 530 patients (26.9%) had both proximal and distal polyps, and 809
      patients (41.0%) had polyps only in the rectosigmoid region. The prevalence of
      the proximal polyps in patients with rectosigmoid polyps was found to be
      significantly related to the male gender and elderly patients. However, the
      prevalence of the proximal colonic polyps was not related to the size and number
      of rectosigmoid polyps. In 530 patients with both rectosigmoid and proximal
      colonic polyps, the characteristics of proximal colonic polyps as size and number
      were similar to those of rectosigmoid polyps. Advanced proximal adenomas without
      distal polyps were found in 25 (29.4%) patients whom were associated with size
      and pathology. CONCLUSIONS: We recommend total colonoscopic examination in all
      patients regardless of the size and number, especially in elderly males.

PMID- 23954960
TI  - Temporary placement of fully covered self-expandable metal stents in benign
      biliary strictures.
AB  - BACKGROUND/AIMS: Benign biliary strictures (BBSs) have been endoscopically
      managed with plastic stent placement. However, data regarding fully covered self
      expandable metal stents (FCSEMSs) in BBS patients remain scarce in Korea.
      METHODS: Forty-one patients (21 men, 65.9%) with BBSs underwent FCSEMS placement
      between February 2007 and July 2010 in Asan Medical Center. Efficacy and safety
      were evaluated retrospectively. Patients were considered to have resolution if
      they showed evidence of stricture resolution on cholangiography and if an
      inflated retrieval balloon easily passed through the strictures at FCSEMS
      removal. RESULTS: The mean FCSEMS placement time was 3.2 (1.9-6.2) months.
      Patients were followed for a mean of 10.2 (1.0-32.0) months after FCSEMS removal.
      The BBS resolution rate was confirmed in 38 of 41 (92.7%) patients who underwent
      FCSEMS removal. After FCSEMS removal, 6 of 38 (15.8%) patients experienced
      symptomatic recurrent stricture and repeat stenting was performed. When a
      breakdown by etiology of stricture was performed, 14 of 15 (93.3%) patients with
      chronic pancreatitis, 17 of 19 (89.5%) with gall stone-related disease, 4 of 4
      (100%) with surgical procedures, and 2 of 2 (100%) with BBSs of other etiology
      had resolution at FCSEMS removal. Complications related to stent therapy occurred
      in 12 (29%) patients, including post-ERCP pancreatitis (n=4), proximal migration
      (n=3), distal migration (n=3), and occlusion (n=2). CONCLUSIONS: Temporary FCSEMS
      placement in BBS patients offers a potential alternative to plastic stenting.
      However, because of the significant complications and modest resolution rates,
      the potential benefits and risks should be evaluated in further investigations.

PMID- 23954958
TI  - [Benzoxazole derivative B-98 ameliorates dextran sulfate sodium-induced acute
      murine colitis and the change of T cell profiles in acute murine colitis model].
AB  - BACKGROUND/AIMS: The unique role of enzyme 5-lipoxygenase (5-LO) in the
      production of leukotrienes makes it a therapeutic target for inflammatory bowel
      disease (IBD). The aim of this study was to evaluate the effects of B-98, a newly
      synthesized benzoxazole derivatives and a novel 5-LO inhibitor, in a mouse model
      of IBD induced by dextran sulfate sodium (DSS). METHODS: C57BL/6 mice were
      randomly assigned to four groups: normal control, DSS colitis (DSS+saline), low
      dose B-98 (DSS+B-98 20 mg/kg) and high dose B-98 (DSS+B-98 100 mg/kg). B-98 was
      administered with 3% DSS intraperitoneally. The severity of the colitis was
      assessed via the disease activity index (DAI), colon length, and histopathologic
      grading. The production of inflammatory cytokines interleukin (IL)-6 was
      determined by RT-PCR. Th cells were examined for the proportion of Th1 cell, Th2
      cell, Th9 cell, Th17 cell and Treg cell using intracellular cytometry. RESULTS:
      The B-98 group showed lower DAI, less shortening of the colon length and lower
      histopathologic grading compared with the DSS colitis group (p<0.01). The
      expression of IL-6 in colonic tissue was significantly lower in the B-98 groups
      than the DSS colitis group (p<0.05). The cellular profiles revealed that the Th1,
      Th9 and Th17 cells were increased in the DSS colitis group compared to the B-98
      group (p<0.05). CONCLUSIONS: Our results suggest that acute intestinal
      inflammation is reduced in the group treated with B-98 by Th1, Th9 and Th17
      involved cellular immunity.

PMID- 23954961
TI  - [A case of isolated small intestinal wall calcification on patient with
      continuous ambulatory peritoneal dialysis].
AB  - The metastatic calcification is defined as the deposition of calcium salt in
      normal tissue with an abnormal serum biochemical environment, such as chronic
      kidney disease, hyperparathyroidism, and hypercalcemia related with malignancy.
      Although the metastatic calcification can develop in any organs and tissues,
      presenting its symptoms and complications are rare. Thus a few cases have been
      reported. This case shows the metastatic calcification of the small intestine
      without any peritoneal and mesenteric vascular calcification which was early
      diagnosed by computed tomography and mesenteric angiography in a patient with
      abdominal pain, receiving continuous ambulatory peritoneal dialysis due to end
      stage renal disease. The clinician should early consider the metastatic
      calcification as differential diagnosis when unidentified calcifications are
      noted in simple abdominal X-ray such as in the present case, and promptly confirm
      it by using appropriate diagnostic tests in order to prevent its complications
      and progression.

PMID- 23954962
TI  - [A case of simultaneously occurred amiodarone-induced hepatitis and
      hypothyroidism].
AB  - Amiodarone is a di-iodated benzofuran derivative that is commonly used to treat
      patients with various cardiac arrhythmias. It is associated with side effects
      that involve the liver, thyroid, and other organs. Approximately 1-3% of patients
      treated with amiodarone suffer from symptomatic liver disease. Thyroid
      dysfunction occurs in 10% of patients treated with amiodarone. A 65-year-old
      woman with coronary heart disease and atrial fibrillation was administered with
      amiodarone. She developed nausea, vomiting, dyspepsia, and sweating within 9
      months of amiodarone administration (200 mg orally once a day). Results of the
      laboratory finding showed increased hepatic enzymes, and low thyroid hormone
      levels. A liver biopsy showed irregular arrangement of hepatocytes and diffuse
      micro- and macrovesicular fatty changes. Electron microscopy findings showed
      pleomorphic mitochondria with crystalloid inclusions and membrane-bound lysosomal
      structures. The liver and thyroid functions returned to normal, after the
      amiodarone was stopped. We describe an unusual case in which amiodarone induced
      hepatitis and hypothyroidism simultaneously. Physicians should take a close look
      to the adverse event when using amiodarone which can cause adverse effects in
      multiple organs.

PMID- 23954963
TI  - [A case of tuberculous liver abscess developed during chemotherapy for
      tuberculous peritonitis as paradoxical response].
AB  - Tuberculous liver abscesses are rare. Paradoxical response in tuberculosis is
      common and occurred between 2 weeks and 12 weeks after anti-tuberculous
      medication. We report here a case of tuberculous liver abscess that developed in
      a paradoxical response during chemotherapy for tuberculous peritonitis in a 23
      year-old male. He was hospitalized, complaining of ascites, epigastric pain. He
      was diagnosed tuberculous peritonitis by expiratory laparoscopic biopsy and took
      medication for tuberculosis. After 2 months, a hepatic lesion was detected with
      CT scan incidentally. Chronic granulomatous inflammation was seen in ultrasound
      guided liver biopsy, and tuberculous liver abscess was diagnosed. It was
      considered as paradoxical response, rather than treatment failure or other else
      because clinical symptoms of peritoneal tuberculosis and CT scan improved. After
      continuing initial anti-tuberculous medication, he was successfully treated.
      Herein, we report a case of tuberculous liver abscess as paradoxical response
      while treating peritoneal tuberculosis without changing anti-tuberculous
      treatment regimen.

PMID- 23954964
TI  - [A case of IgG4 associated sclerosing cholangitis without clinical manifestations
      of autoimmune pancreatitis].
AB  - IgG4-related systemic diseases are characterized by a diffuse or mass forming
      inflammatory reaction rich in lymphocytes and IgG4-positive plasma cells
      (lymphoplasmacytic infiltration), fibrosclerosis of variable organs and
      obliterative phlebitis. They usually involve various organs including the
      pancreas, bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung,
      and prostate. However, most of them are accompanied by autoimmune pancreatitis,
      and good response to steroid treatment is one of the hallmarks of this disease.
      We report a case of an 67-year-old man with IgG4 associated sclerosing
      cholangitis, who was diagnosed by endoscopic retrograde cholangiopancreatography
      and successfully treated with steroid therapy.

PMID- 23954965
TI  - Image-guided nerve cryoablation for post-thoracotomy pain syndrome.
AB  - Chronic post-thoracotomy pain syndrome (PTPS) can cause significant patient
      distress and is frequently difficult to manage. Percutaneous intercostal nerve
      (ICN) cryoablation by palpation of surface landmarks can be risky, as inaccurate
      probe placement can lead to hemo- or pneumothorax. Experience with image-guided
      ICN cryoablation with treatment planning and device navigation is limited. A
      patient with intractable PTPS was treated with ICN cryoablation under cone-beam
      computed tomography guidance with software-assisted needle trajectory planning
      and ablation zone simulation. This procedure provided the patient ~8 weeks of
      relief. This case demonstrated that ICN cryoablation is feasible under image
      guidance with device navigation and ablation simulation and may result in a few
      months of pain relief in cases of intractable PTPS.

PMID- 23954967
TI  - Autophagy reduces neuronal damage and promotes locomotor recovery via inhibition
      of apoptosis after spinal cord injury in rats.
AB  - Autophagy is an intracellular catabolic mechanism that maintains the balance of
      proteins, lipids and aging organelles. 3-Methyladenine (3-MA) is a selective
      inhibitor of autophagy, whereas rapamycin, an antifungal agent, is a specific
      inducer of autophagy, inhibiting the protein mammalian target of rapamycin. In
      the present study, we examined the role of autophagy, inhibited by 3-MA and
      enhanced by rapamycin, in a model of acute spinal cord injury in rats. We found
      that rapamycin could significantly increase the expression of microtubule
      associated protein 1 light chain 3 (LC3) and Beclin1 at the injury site. At the
      same time, the number of neurons and astrocytes with LC3 positive in the spinal
      cord was upregulated with time. In addition, administration of rapamycin produced
      an increase in the Basso, Beattie and Bresnahan scores of injured rats,
      indicating high recovery of locomotor function. Furthermore, expression of the
      proteins Bcl-2 and Bax was upregulated and downregulated, respectively. By
      contrast, the results for rats treated with 3-MA, which inhibits autophagy, were
      the opposite of those seen with the rapamycin-treated rats. These results show
      that induction of autophagy can produce neuroprotective effects in acute spinal
      cord injury in rats via inhibition of apoptosis. 

PMID- 23954968
TI  - Nanoparticle for delivery of antisense gammaPNA oligomers targeting CCR5.
AB  - The development of a new class of peptide nucleic acids (PNAs), i.e., gamma PNAs
      (gammaPNAs), creates the need for a general and effective method for its delivery
      into cells for regulating gene expression in mammalian cells. Here we report the
      antisense activity of a recently developed hydrophilic and biocompatible
      diethylene glycol (miniPEG)-based gamma peptide nucleic acid called MPgammaPNAs
      via its delivery by poly(lactide-co-glycolide) (PLGA)-based nanoparticle system.
      We show that MPgammaPNA oligomers designed to bind to the selective region of
      chemokine receptor 5 (CC R5) transcript, induce potent and sequence-specific
      antisense effects as compared with regular PNA oligomers. In addition, PLGA
      nanoparticle delivery of MPgammaPNAs is not toxic to the cells. The findings
      reported in this study provide a combination of gammaPNA technology and PLGA
      based nanoparticle delivery method for regulating gene expression in live cells
      via the antisense mechanism.

PMID- 23954969
TI  - Genome-wide association studies in Alzheimer's disease: a review.
AB  - Over the past decade, research aiming to disentangle the genetic underpinnings of
      late-onset Alzheimer's disease has mostly focused on the identification of common
      variants through genome-wide association studies. The identification of several
      new susceptibility genes through these efforts has reinforced the importance of
      amyloid precursor protein and tau metabolism in the cause of the disease and has
      implicated immune response, inflammation, lipid metabolism,
      endocytosis/intracellular trafficking, and cell migration in the cause of the
      disease. Ongoing and future large-scale genome-wide association studies,
      translational studies, and next-generation whole genome or whole exome sequencing
      efforts, hold the promise to map the specific causative variants in these genes,
      to identify several additional risk variants, including rare and structural
      variants, and to identify novel targets for genetic testing, prevention, and
      treatment.

PMID- 23954970
TI  - Medication nonadherence in Parkinson's disease.

PMID- 23954971
TI  - Septic encephalopathy.
AB  - Every year, more cases of sepsis appear in intensive care units. The most
      frequent complication of sepsis is septic encephalopathy (SE), which is also the
      essential determinant of mortality. Despite many years of research, it still is
      not known at which stage of sepsis the first signs of SE appear; however, it is
      considered the most frequent form of encephalopathy. Patients have dysfunction of
      cognitive abilities and consciousness, and sometimes even epileptic seizures.
      Despite intensive treatment, the effects of SE remain for many years and
      constitute an important social problem. Numerous studies indicate that changes in
      the brain involve free radicals, nitric oxide, increased synthesis of
      inflammatory factors, disturbances in cerebral circulation, microthromboses, and
      ischemia, which cause considerable neuronal destruction in different areas of the
      brain. To determine at what point during sepsis the first signs of SE appear,
      different experimental models are needed to detect the aforementioned changes and
      to select the proper therapy for this syndrome.

PMID- 23954972
TI  - Update on HIV-associated neurocognitive disorders.
AB  - Neurocognitive disorders are a feared complication of HIV infection, especially
      in the post-antiretroviral era as patients are living longer. These disorders are
      challenging in terms of diagnosis and treatment. The clinical syndrome has
      evolved, driven in part by comorbidities such as aging, drug abuse, psychiatric
      illnesses, and a metabolic syndrome associated with the use of antiretroviral
      drugs. Additionally some individuals may develop a fulminant immune
      reconstitution syndrome. Hence, treatment of these patients needs to be
      individualized. The focus of research in the HIV field has recently switched
      towards elimination of the HIV reservoir as a means of combating long-term HIV
      complications. However, these approaches may be suitable for limited populations
      and might not be applicable once the HIV reservoir has been established in the
      brain. Further, all clinical trials using neuroprotective or anti-inflammatory
      drugs for treatment of HIV-associated neurocognitive disorders have been
      unsuccessful. Hence, neurological complications of HIV infection are the biggest
      challenge facing HIV researchers, and there is a critical need to develop new
      diagnostics and approaches for treatment of these disorders.

PMID- 23954975
TI  - [Fascination with dermatologic surgery].

PMID- 23954973
TI  - Melanoma brain metastases: an unmet challenge in the era of active therapy.
AB  - Metastatic disease to the brain is a frequent manifestation of melanoma and is
      associated with significant morbidity and mortality and poor prognosis. Surgery
      and stereotactic radiosurgery provide local control but less frequently affect
      the overall outcome of melanoma brain metastases (MBM). The role of systemic
      therapies for active brain lesions has been largely underinvestigated, and
      patients with active brain lesions are excluded from the vast majority of
      clinical trials. The advent of active systemic therapy has revolutionized the
      care of melanoma patients, but this benefit has not been systematically
      translated into intracranial activity. In this article, we review the biology and
      clinical outcomes of patients with MBM, and the evidence supporting the use of
      radiation, surgery, and systemic therapy in MBM. Prospective studies that
      included patients with active MBM have shown clinical intracranial activity that
      parallels systemic activity and support the inclusion of patients with active MBM
      in clinical trials involving novel agents and combination therapies.

PMID- 23954976
TI  - [Platelet inhibitors and anticoagulants: managing blood thinners in
      dermatosurgery].
AB  - Many patients requiring dermatologic surgery are taking anticoagulants or
      antiplatelet agents. The perioperative management of these drugs is not
      standardized and affected by fear of bleeding complications. Studies show only
      moderate increase in bleeding complications while taking these drugs. Our
      clinical experience shows no significant peri- or postoperative bleeding. As part
      of a risk assessment, thromboembolic complications outweigh any bleeding risk of
      surgery. Therefore, in the experience of the authors, blood thinning drugs should
      be continued before and during dermatosurgical procedures. General assessment of
      laboratory parameters concerning coagulation or platelet function is not
      necessary and can be restricted to selected subgroups of patients. 

PMID- 23954978
TI  - [Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): a review].
AB  - DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms), also known as
      hypersensitivity syndrome (HSS), is a severe and potentially life-threatening
      drug reaction. The worldwide rate of mortality is about 10 %, its incidence is
      increasing. Drugs that most frequently induce DRESS are aromatic anticonvulsive
      drugs (carbamazepine, lamotrigine, phenobarbital), and more recently new
      retroviral therapies. The pathogenesis of DRESS is not yet fully understood, but
      is certainly multifactorial involving a combination of immune reactions, ethnic
      predisposition, genetically determined enzyme deficiencies and reactivation of
      herpes viruses (HHV-6, HHV-7, EBV, CMV). Because of the involvement of the skin
      and internal organs, the clinical picture can be very variable. No specific
      clinical, histologic or laboratory parameter is available, so the diagnosis has
      to rely on the clinical appearance. The long latency period between start of drug
      intake and the initial manifestation of DRESS and the successive onset of skin
      and organ involvement complicates the early diagnosis. Although or even because
      DRESS represents a diagnostic challenge, detailed knowledge about this disease is
      of utmost importance to enable early therapeutic actions.

PMID- 23954980
TI  - [Improving Structures for Healthy and Self-Determined Ageing in an Urban
      District].
AB  - Between 2007 and 2010 the Institut fur Gerontologische Forschung e.V.
      investigated the "Primary Prevention Effects of the Markisches Viertel Network"
      in the Berlin district "Markisches Viertel". The study integrates, amongst
      others, various participatory methods to investigate the health promotion effects
      of the volunteer Markisches Viertel Network, an organisation that brings together
      different local actors working to assist and encourage older people to live
      independent lives. Sustained active collaboration by a heterogeneous mixture of
      actors in a spatially defined quarter, engagement by the local housing
      association, and increasing acknowledgement of and participation by older
      residents were identified as success factors for a change in local structures.

PMID- 23954979
TI  - Electroporation mediated DNA vaccination directly to a mucosal surface results in
      improved immune responses.
AB  - In vivo electroporation (EP) has been shown to be a highly efficient non-viral
      method for enhancing DNA vaccine delivery and immunogenicity, when the site of
      immunization is the skin or muscle of animals and humans. However, the route of
      entry for many microbial pathogens is via the mucosal surfaces of the human body.
      We have previously reported on minimally invasive, surface and contactless EP
      devices for enhanced DNA delivery to dermal tissue. Robust antibody responses
      were induced following vaccine delivery in several tested animal models using
      these devices. Here, we investigated extending the modality of the surface device
      to efficiently deliver DNA vaccines to mucosal tissue. Initially, we demonstrated
      reporter gene expression in the epithelial layer of buccal mucosa in a guinea pig
      model. There was minimal tissue damage in guinea pig mucosal tissue resulting
      from EP. Delivery of a DNA vaccine encoding influenza virus nucleoprotein (NP) of
      influenza H1N1 elicited robust and sustained systemic IgG antibody responses
      following EP-enhanced delivery in the mucosa. Upon further analysis, IgA antibody
      responses were detected in vaginal washes and sustained cellular immune responses
      were detected in animals immunized at the oral mucosa with the surface EP device.
      This data confirms that DNA delivery and EP targeting mucosal tissue directly
      results in both robust and sustainable humoral as well as cellular immune
      responses without tissue damage. These responses are seen both in the mucosa and
      systemically in the blood. Direct DNA vaccine delivery enhanced by EP in mucosa
      may have important clinical applications for delivery of prophylactic and
      therapeutic DNA vaccines against diseases such as HIV, HPV and pneumonia that
      enter at mucosal sites and require both cellular and humoral immune responses for
      protection. 

PMID- 23954981
TI  - [Capacity Building for Prevention and Health Promotion for Children and Parents
      in a Deprived Urban Quarter: Lenzgesund].
AB  - In 2005 the local health authority Hamburg-Eimsbuttel developed a prevention
      programme for the disadvantaged quarter "Lenzsiedlung" which has been implemented
      by the stakeholders committee "Round Table Lenzgesund" and other partners led by
      the health authority. The Department of Medical Sociology and Health Economics of
      the University Medical Centre had taken on the accompanying analysis and long
      term evaluation with a mixture of qualitative and quantitative methods for health
      reporting and evaluation and a new instrument for measuring capacity building in
      the quarter (KEQ). 

PMID- 23954982
TI  - [Primary Prevention of Impairments of Mobility Among Nursing Home Residents with
      Dementia].
AB  - The main aim of the study was to investigate the effectiveness of
      multidisciplinary guidelines in promoting the mobility of people with dementia in
      20 German nursing homes. The study was based on a semi-experimental design [pre
      post design with intervention (IG) and control group]. The statistical analyses
      revealed a significantly slower decline of the ability to walk among the
      residents of the IG than among the controls. With regard to other outcome
      measures the results were less clear. 

PMID- 23954983
TI  - [Stress Management Interventions at the Workplace Improve Perceived Stress
      Reactivity of Men at Higher Risk].
AB  - A randomised controlled trial was conducted in a metal working plant. The primary
      endpoint was perceived stress reactivity (Stress Reactivity Scale, SRS). 174
      participants were randomly assigned to a stress-management intervention (SMI)
      (IG) or a waiting control group (CG). N=174 participants (171 male) were
      recruited at t0, 154 (89%) were still taking part after one year (t1), 131 (76%)
      after 2 years. The SRS score decreased in both groups. The conducted SMI proved
      to be effective over both a 1- and a 2-year period. 

PMID- 23954984
TI  - [Effectiveness and Cost-Effectiveness of Daily School Sport in the Primary School
      -Project: "fit for pisa"].
AB  - The "fit for pisa" intervention implemented daily physical education at five
      primary schools in Gottingen. The results of the evaluation show an increase in
      physical activity among the students participating in the programme. At the same
      time sedentary behaviour, like watching television, decreased remarkably. In the
      long run the promotion of an active lifestyle had improved the body mass index.
      The study emphasises the need for government funding to implement the programme
      across the country.

PMID- 23954985
TI  - [The Social Experience of Being Obese. Obesity Prevention of Socially Deprived
      Adolescents].
AB  - Group discussions with obese teenagers and parents with obese children are the
      empirical basis of this research project. The results indicate that 'being fat'
      is primarily a social experience. Consequently, preventive measures to inhibit
      unhealthy lifestyle habits fail to go into sufficient depth. Overweight
      adolescents call for equality; they demand a more equal treatment in social
      interactions and relations. 

PMID- 23954986
TI  - [MRSA bloodstream infections according to the German obligation for notification 
      data and experience of the MDRO Network Rhine-Main, Germany, 2011].
AB  - BACKGROUND: Since July 1st, 2009 in accord with the statuary order based on the
      German law for infectious diseases (Infektionsschutzgesetz), MRSA in blood and
      liquor have to be notified to the public health authorities. The aim of this
      extension of the notification to report is to improve the surveillance of
      nosocomial infections and the prevention of nosocomial MRSA infections. In this
      paper data of the notifications in the year 2011 within the MDRO-Net Rhine-Main,
      an association of 7 public health authorities in the region, are reported in
      order to investigate whether the aims of the obligation for notification could be
      achieved. RESULTS: In 2011, 138 MRSA bloodstream infections, including 1 MRSA in
      liquor culture, were notified to the 7 health protection authorities, resulting
      in an incidence rate of 5.6/100,000 inhabitants. In urban regions with more
      hospitals available, the incidence rate was higher than in rural districts with
      less medical facilities (6.9 vs. 4.4/100,000 inhabitants). Only 46 (35%) of the
      patients with MRSA cultured in their blood had been detected via anamnesis as
      patients on risk for MRSA, and 59 (45%) had been screened for MRSA on admission.
      The incidence rate in the different hospitals was 0.041 +/- 0.031/1,000 patient
      days (range 0-0.145/1,000 patient days). CONCLUSIONS: For the first time, data on
      notification of MRSA cultures in blood specimen are published from a whole MRE
      Network in Germany encompassing >2.1 million inhabitants. Incidence rates per
      100,000 inhabitants alone do not seem adequate to cope with the aims of the
      obligation for notification. Instead, reference to patient days in the respective
      clinic enables an external comparison to other medical institutions in the region
      and is a better base for discussion with these institutions on improvements of
      surveillance, screening and hygiene.

PMID- 23954987
TI  - [The professional and private situation of male and female physicians entering
      postgraduate medical education in Germany].
AB  - AIM: This study investigated the professional and the private situation of
      medical interns at the onset of their postgraduate training in Germany. We
      analysed the contractual situation and the working hours in the hospital, the
      professional situation of the partner and the number of hours invested in private
      life with special reference to gender and children. METHOD: A standardised postal
      survey was conducted among all last year medical students in the medical
      faculties of Erlangen, Giessen, Hamburg, Heidelberg, Cologne, Leipzig and
      Magdeburg after entering postgraduate training. 1 009 were contacted for a first
      follow-up one year later and 87% responded. Descriptive statistics and regression
      analysis were performed. RESULTS: The analysis shows that female physicians are
      disadvantaged compared to males with regard to various professional and private
      conditions relevant for career development, especially when children are present.
      We found a large number of hints pointing towards a persistence of traditional
      role patterns within the couple relationship. These conditions differed
      substantially between the regions of former German Federal and former German
      Democratic Republic. CONCLUSIONS: A growing number of children in the study
      population in the course of the longitudinal analysis will show if these gender
      related differences persist in the course of the training period and which
      influences on career development can be observed.

PMID- 23954989
TI  - Magnetic sentinel lymph node biopsy and localization properties of a magnetic
      tracer in an in vivo porcine model.
AB  - The standard for the treatment of early non-palpable breast cancers is wide local
      excision directed by wire-guided localization and sentinel lymph node biopsy
      (SLNB). This has drawbacks technically and due to reliance upon radioisotopes. We
      evaluated the use of a magnetic tracer for its localization capabilities and
      concurrent performance of SLNB using a handheld magnetometer in a porcine model
      as a novel alternative to the current standard. Ethical approval by the IRCAD
      Ethics Review Board, Strasbourg (France) was received. A magnetic tracer was
      injected in varying volumes (0.1-5 mL) subcutaneously into the areolar of the
      left and right 3rd inguinal mammary glands in 16 mini-pigs. After 4 h
      magnetometer counts were taken at the injection sites and in the groins. The
      magnetometer was used to localize any in vivo signal from the draining inguinal
      lymph nodes. Magnetic SLNB followed by excision of the injection site was
      performed. The iron content of sentinel lymph nodes (SLNs) were graded and
      quantified. All excised specimens were weighed and volumes were calculated.
      Univariate analyses were performed to evaluate correlation. Magnetic SLNB was
      successful in all mini-pigs. There was a significant correlation (r = 0.86; p <
      0.01) between magnetometer counts and iron content of SLNs. Grading of SLNs on
      both H&E and Perl's staining correlated significantly with the iron content (p =
      0.001; p = 0.003) and magnetometer counts (p < 0.001; p = 0.004). The peak counts
      corresponded to the original magnetic tracer injection sites 4 h after injection
      in all cases. The mean volume and weight of excised injection site specimens was
      2.9 cm(3) (SD 0.81) and 3.1 g (SD 0.85), respectively. Injection of >=0.5 mL
      magnetic tracer was associated with significantly greater volume (p = 0.05) and
      weight of excision specimens (p = 0.01). SLNB and localization can be performed
      in vivo using a magnetic tracer. This could provide a viable alternative for
      lesion localization and concurrent SLNB in the treatment of non-palpable breast
      cancer.

PMID- 23954988
TI  - Golgi apparatus analyzed by cryo-electron microscopy.
AB  - In 1898, the Golgi apparatus was discovered by light microscopy, and since the
      1950s, the ultrastructure composition is known by electron microscopic
      investigation. The complex three-dimensional morphology fascinated researchers
      and was sometimes even the driving force to develop novel visualization
      techniques. However, the highly dynamic membrane systems of Golgi apparatus are
      delicate and prone to fixation artifacts. Therefore, the understanding of Golgi
      morphology and its function has been improved significantly with the development
      of better preparation methods. Nowadays, cryo-fixation is the method of choice to
      arrest instantly all dynamic and physiological processes inside cells, tissues,
      and small organisms. Embedded in amorphous ice, such samples can be further
      processed by freeze substitution or directly analyzed in their fully hydrated
      state by cryo-electron microscopy and tomography. Even though the overall
      morphology of vitrified Golgi stacks is comparable to well-prepared and resin
      embedded samples, previously unknown structural details can be observed solely
      based on their native density. At this point, any further improvement of sample
      preparation would gain novel insights, perhaps not in terms of general
      morphology, but on fine structural details of this dynamic organelle. 

PMID- 23954990
TI  - Predictive factors associated with the acceptance of pandemic and seasonal
      influenza vaccination in health care workers and students in Tuscany, Central
      Italy.
AB  - Assessing the beliefs and attitudes of Health Care Workers (HCW) to influenza and
      influenza vaccination can be useful in overcoming low compliance rates. The
      purpose of our study is to evaluate the opinion of HCW and students regarding
      influenza, influenza vaccine and the factors associated with vaccination
      compliance. A survey was conducted between October 2010 and April 2011 in the
      Florence metropolitan area. A questionnaire was administered to HCW in three
      local healthcare units and at Careggi University Teaching Hospital. Students
      matriculating in health degree programs at Florence University were also
      surveyed. The coverage with vaccination against seasonal and pandemic influenza
      is generally low, and it is lower in students than in HCW (12.5% vs 15% for the
      seasonal vaccination, 8.5% vs 18% for the pandemic vaccination). Individuals
      comply with vaccination offer mainly to protect themselves and their contacts.
      Individuals not receiving vaccination did not consider themselves at risk, had
      never been vaccinated before or believed that pandemic influenza was not a public
      health concern. Physicians had the highest compliance to vaccination and women
      were less frequently vaccinated than men. HCW do not appear to perceive their
      possible influenza infections as a risk for patients: HCW receive vaccination
      mainly as a form of personal protection. Low compliance to vaccination is
      determined by various factors and therefore requires a multi-faceted strategy of
      response. This should include short-term actions to overcome organizational
      barriers, in addition to long-term interventions to raise HCW's level of
      knowledge about influenza and influenza vaccination. 

PMID- 23954991
TI  - Exercise attenuates M1 macrophages and CD8+ T cells in the adipose tissue of
      obese mice.
AB  - PURPOSE: Obesity is associated with adipose tissue inflammation, which has been
      attributed to changes in the number and types of leukocytes in adipose tissue.
      Exercise training is thought to be important for the reduction of adipose tissue
      inflammation, but the mechanisms by which this may occur are incompletely
      understood. Here, we evaluated the effect of exercise training on several
      inflammation-associated changes in adipose tissue, including infiltration of
      inflammatory macrophages and T cells. METHODS: Four-week-old male C57BL/6J mice
      were randomly assigned to four groups that received a normal diet (ND) plus
      sedentary (n = 8), an ND plus exercise training (n = 8), a high-fat diet (HFD)
      plus sedentary (n = 12), and an HFD plus exercise training (n = 12). Mice were
      fed the ND or the HFD from 4 to 20 wk of age. Mice in the exercise groups ran on
      a treadmill for 60 min.d, 5 d.wk over the same points. RESULTS: Mice fed the HFD
      had increased numbers of macrophage clusters in adipose tissue, which were
      reduced by exercise training. Similarly, adipose tissue from the HFD sedentary
      mice contained higher levels of tumor necrosis factor alpha mRNA and increased
      numbers of CD11c inflammatory macrophages and CD8 T cells than adipose tissue
      from the ND mice, and those were also lowered by exercise training. The mRNA
      levels of monocyte chemoattractant proteins 1 and 2 and macrophage inflammatory
      proteins 1alpha and 1beta in adipose tissue were lower in the HFD exercise mice
      than those in the HFD sedentary mice. CONCLUSIONS: The results suggest that
      exercise training reduces adipose tissue inflammation by suppressing infiltration
      of inflammatory macrophages and CD8 T cells.

PMID- 23954993
TI  - Effect of high dietary restraint on energy availability and menstrual status.
AB  - INTRODUCTION: Dietary restraint (DR) is a key eating behavior associated with
      menstrual disturbances (MD) in exercising women. However, the association between
      DR and energy availability (EA) has not been examined. PURPOSES: The objective of
      this study is 1) to compare EA in women when categorized by DR score, to include
      an evaluation of the frequency of women with low EA, and 2) to compare the
      distribution of subclinical and clinical MD between DR groups. METHODS:
      Exercising women (23 +/- 4 yr; body mass index, 21.1 +/- 1.9 kg.m; and exercise
      volume, 333 +/- 198 min.wk) were retrospectively categorized by DR score into two
      groups: 1) women with high DR (n = 30) and 2) women with normal DR (n = 56). DR
      scores were obtained from the Three-Factor Eating Questionnaire. High DR score
      was defined as >=13. Body composition was measured using dual-energy x-ray
      absorptiometry. EA was defined as energy intake - exercise energy expenditure per
      kilogram lean body mass (LBM). Low EA was defined as <30 kcal.kg LBM. Menstrual
      status was determined using daily urinary samples assayed for reproductive
      hormones. RESULTS: EA was lower in the high DR versus the normal DR group (35.0
      +/- 12.9 vs 42.0 +/- 12.9 kcal.kg LBM, P = 0.018). There was no difference (P =
      0.866) in frequency of low EA between DR groups. There was a greater frequency of
      MD (amenorrhea, oligomenorrhea, anovulation, or luteal phase defect) in the high
      DR group (21/28, 75.0%) versus the normal DR group (24/47, 51.1%) (chi = 4.2, P =
      0.041). CONCLUSION: Our findings demonstrate that exercising women with high DR
      exhibited lower EA and a greater frequency of MD (subclinical and clinical)
      compared with women with normal DR. However, high DR was not associated with low
      EA in exercising women.

PMID- 23954992
TI  - Exercise benefits in chronic graft versus host disease: a murine model study.
AB  - INTRODUCTION: Chronic graft versus host disease (cGVHD) is a life-threatening
      complication of allogeneic hematopoietic stem cell transplantation that generates
      considerable morbidity and compromises the physical capacity of patients. We
      determined the effects of an exercise training program performed after allogeneic
      hematopoietic stem cell transplantation on clinical and biological variables in a
      minor histocompatibility antigen-driven murine model of cGVHD treated with
      cyclosporine A. METHODS: Recipient BALB/C female mice (age 8 wk) received bone
      marrow cells and splenocytes from donor B10.D2 male mice and were randomly
      assigned to an exercise (n = 11) or control group (n = 12). For approximately 11
      wk after transplant, the exercise group completed a moderate-intensity treadmill
      program. Variables assessed were clinical severity scores, survival, physical
      fitness, cytokine profile, immune cell reconstitution, molecular markers of
      muscle exercise adaptations, and histological scores in affected tissues.
      RESULTS: Exercise training increased survival (P = 0.011), diminished total
      clinical severity scores (P = 0.002), improved physical fitness (P = 0.030), and
      reduced blood IL-4 and tumor necrosis factor alpha levels (P = 0.03), while
      increasing circulating B220 (P = 0.008) and CD4 lymphocytes (P = 0.043).
      CONCLUSIONS: A moderate-intensity exercise program that mimics widely accepted
      public health recommendations for physical activity in human adults was well
      tolerated and positive effects on survival as well as on clinical and biological
      indicators of cGVHD.

PMID- 23954994
TI  - Photo ionisation in mass spectrometry: light, selectivity and molecular ions.

PMID- 23954995
TI  - Liquid chromatography-mass spectrometry for metabolic footprinting of co-cultures
      of lactic and propionic acid bacteria.
AB  - Co-cultures of specific lactic and propionic acid bacteria have been shown to
      have an antagonistic effect against yeast and moulds in dairy systems. In studies
      of these co-cultures by bioassay-guided fractionation and analysis, numerous
      compounds have been reported to inhibit yeast and moulds. Although active, the
      compounds do not account for the full effect observed. Instead, the inhibitory
      action in the co-culture is believed to be a result of synergy between known exo
      metabolites, depletion of nutrients, and/or compounds not yet identified.
      Untargeted metabolomics or metabolic footprinting could be a potent approach to
      elucidation of the mechanism. The purpose of this review is to discuss the two
      pre-requisites for such a study--the compound classes expected in the co
      cultures, and on the basis of these, the most suitable analytical technique(s).
      Ultrahigh-performance liquid chromatography (UPLC) coupled to high-resolution
      mass spectrometry (MS) via electrospray ionisation (ESI) operated in both
      positive and negative modes is regarded as the optimum instrumental technique.
      The applicability of a range of liquid chromatographic techniques ranging from
      ion-pair (IPC) and hydrophilic interaction (HILIC) to reversed-phase
      chromatography (RPC) is discussed in terms of the expected metabolome. Use of
      both HILIC and RPC is suggested, on account of the complementarity of these
      modes. The most promising strategy uses a combination of the two electrospray
      polarities and two modes of LC. The strategy recommended in this study does not
      include all compound classes, and suggestions for supplementary methods are
      listed.

PMID- 23954996
TI  - A high-sensitivity ultra-high performance liquid chromatography/high-resolution
      time-of-flight mass spectrometry (UHPLC-HR-TOFMS) method for screening synthetic
      cannabinoids and other drugs of abuse in urine.
AB  - The continuing emergence of designer drugs imposes high demands on the scope and
      sensitivity of toxicological drug screening procedures. An ultra-high performance
      liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR
      TOFMS) method was developed for screening and simultaneous confirmation of both
      designer drugs and other drugs of abuse in urine samples in a single run. The
      method covered selected synthetic cannabinoids and cathinones, amphetamines,
      natural cannabinoids, opioids, cocaine and other important drugs of abuse,
      together with their main urinary metabolites. The database consisted of 277
      compounds with molecular formula and exact monoisotopic mass; retention time was
      included for 192 compounds, and primary and secondary qualifier ion exact mass
      for 191 and 95 compounds, respectively. Following a solid-phase extraction,
      separation was performed by UHPLC and mass analysis by HR-TOFMS. MS, and broad
      band collision-induced dissociation data were acquired at m/z range 50-700.
      Compound identification was based on a reverse database search with acceptance
      criteria for retention time, precursor ion mass accuracy, isotopic pattern and
      abundance of qualifier ions. Mass resolving power in spiked urine samples was on
      average FWHM 23,500 and mass accuracy 0.3 mDa. The mean and median cut-off
      concentrations determined for 75 compounds were 4.2 and 1 ng/mL, respectively.
      The range of cut-off concentrations for synthetic cannabinoids was 0.2-60 ng/mL
      and for cathinones 0.7-15 ng/mL. The method proved to combine high sensitivity
      and a wide scope in a manner not previously reported in drugs of abuse screening.
      The method's feasibility was demonstrated with 50 authentic urine samples.

PMID- 23954998
TI  - Analysing calcium dependent and independent regulation of eNOS in endothelium
      triggered by extracellular signalling events.
AB  - The vascular endothelium, the intima of blood vessels, coordinately interacts
      with several biochemical factors expressing endothelial nitric oxide synthase
      (eNOS) to produce nitric oxide (NO), a potent endogenous vasodilator. The present
      study investigated the regulation of eNOS by multiple molecular signal
      transduction pathways, namely vascular endothelial growth factor (VEGF-A) and
      shear stress which are implicated in the process of angiogenesis and vascular
      remodelling respectively. In response to signal transduction upstream by VEGF-A
      and shear stress, different signalling pathways mediated by kinases and
      intracellular calcium potentiates eNOS activation leading to nitric oxide
      release. Our study revealed a distinct pattern of eNOS activation driven by VEGF
      A and shear stress, maintaining the signalling specificity of the respective
      pathways. A transient response to eNOS activation was observed under VEGF-A and
      shear stress stimulus when mediated by calcium dependent cascades, whereas a
      sustained response was produced by calcium independent vascular signalling
      kinases. Furthermore, we found that the basal arterial shear stress enhanced eNOS
      activity when stimulated synergistically even at low VEGF-A levels which might be
      utilized to facilitate specific endothelial cell functions. Moreover, our study
      revealed that the presence of PI3K imparted transient behaviour to PLCgamma1
      supporting the hypothesis that regression and formation of tube structures are
      mediated by PLCgamma1 and PI3K respectively in endothelial cells. This fact is
      corroborated by the absence of transient behaviour when PI3K is inhibited. We
      therefore obtained subtle insights into the control mechanism governing the role
      of specific signalling proteins which are obligate for the regulation of
      endothelial cell function and the consequent modulation of the nitric oxide
      release pattern. 

PMID- 23954997
TI  - Expression pattern of serum cytokines in hepatitis B virus infected patients with
      persistently normal alanine aminotransferase levels.
AB  - PURPOSE: About 60-80 % of chronic hepatitis B virus (HBV) carriers are
      characterized with persistently normal alanine transaminase (ALT). Differences of
      cytokine expression are associated with the prognosis of HBV infection. We
      investigated the expression pattern of 30 cytokines associated with anti-HBV
      immunity in patients with normal ALT. METHODS: Four patient groups (immune
      tolerance, inactive hepatitis B surface antigen carriers, resolved hepatitis B,
      and control; 10 subjects per group) were assigned. Thirty cytokines, including
      IFN-gamma, IL-1beta, IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12p40, IL-12p70, IL
      15, IL-17A, IL-17C, IL-21, IL-22, IL-23p19, IL-28A, IL-29, CCL5, CCL16, CCL20,
      CCL22, CXCL9, CXCL10, CXCL11, TNFRSF8, TNFRSF18, IL-6R, gp130, and TGF-beta1,
      were measured using a human cytokine antibody array. Signal intensities were
      obtained by laser scanner. Protein-protein interactions were analyzed by STRING
      (Search Tool for the Retrieval of Interacting Genes/Proteins). RESULTS:
      Significant differences of signal intensities were observed for IL-2, IL-4, IL-6,
      IL-7, IL-9, IL-10, IL-12p40, IL-12p70, IL-15, IL-21, IL-23p19, IL-28A, and IL-29.
      The lowest intensity was in controls. Among three HBV infection groups,
      significant differences were observed in IL-2, IL-4, IL-12p70, IL-15, IL-21, IL
      23p19, and IL-29. The highest intensity was in the inactive group. All cytokines
      with significant differences were involved JAK-STAT signaling that up-regulate
      FOXP3, SOCS3 and MX1. CONCLUSION: Differential expression of cytokines in JAK
      STAT signaling is an important factor associated with prognosis of HBV infection.
      The elevation of gammaC cytokines, IL-12p70, IL-23p19, and IL-29 may promote
      spontaneous HBeAg seroconversion and HBV clearance.

PMID- 23954999
TI  - Cyanide-arene Meisenheimer complex generated in electrospray ionization mass
      spectrometry using acetonitrile as a solvent.
AB  - The C - C bond formation activated under negative electrospray ionization of an
      acetonitrile solution of 1,3,5-trinitrobenzene is reported. The solvent function
      is to provide a source of cyanide ion, a highly problematic reagent, which is
      found to attack the electron-deficient aromatic ring to form a covalently bound
      anionic complex (Meisenheimer complex). The structure of the complex is
      elucidated by means of collision induced dissociation mass spectrometry and IR
      multiple photon dissociation spectroscopy in the 'fingerprint' region. 

PMID- 23955000
TI  - Quadrupole mass filter: design and performance for operation in stability zone 3.
AB  - The predicted performance of a quadrupole mass filter (QMF) operating in Mathieu
      stability zone 3 is described in detail using computer simulations. The
      investigation considers the factors that limit the ultimate maximum resolution
      (Rmax) and percentage transmission (%Tx), which can be obtained for a given QMF
      for a particular scan line of operation. The performance curve (i.e., the
      resolution (R) versus number (N) of radio frequency (rf) cycles experienced by
      the ions in the mass filter) has been modeled for the upper and lower tip of
      stability zone 3. The saturation behavior of the performance curve observed in
      practice for zone 3 is explained. Furthermore, new design equations are presented
      by examining the intersection of the scan line with stability zone 3. Resolution
      versus transmission characteristics of stability zones 1 and 3 are compared and
      the dependence of performance for zones 1 and 3 is related to particular
      instrument operating parameters. 

PMID- 23955001
TI  - Mechanism of formation of the major estradiol product ions following collisional
      activation of the molecular anion in a tandem quadrupole mass spectrometer.
AB  - The importance of the mass spectral product ion structure is highlighted in
      quantitative assays, which typically use multiple reaction monitoring (MRM), and
      in the discovery of novel metabolites. Estradiol is an important sex steroid
      whose quantitation and metabolite identification using tandem mass spectrometry
      has been widely employed in numerous clinical studies. Negative electrospray
      ionization tandem mass spectrometry of estradiol (E2) results in several product
      ions, including the abundant m/z 183 and 169. Although m/z 183 is one of the most
      abundant product ions used in many quantitative assays, the structure of m/z 183
      has not been rigorously examined. We suggest a structure for m/z 183 and a
      mechanism of formation consistent with collision induced dissociation (CID) of E2
      and several stable isotopes ([D4]-E2, [(13)C6]-E2, and [D1]-E2). An additional
      product ion from E2, namely m/z 169, has also been examined. MS(3) experiments
      indicated that both m/z 183 and m/z 169 originate from only E2 [M - H](-) m/z
      271. These ions, m/z 183 and m/z 169, were also present in the collision induced
      decomposition mass spectra of other prominent estrogens, estrone (E1) and estriol
      (E3), indicating that these two product ions could be used to elucidate the
      estrogenic origin of novel metabolites. We propose two fragmentation schemes to
      explain the CID data and suggest a structure of m/z 183 and m/z 169 consistent
      with several isotopic variants and high resolution mass spectrometric
      measurements. 

PMID- 23955002
TI  - Protons are one of the limiting factors in determining sensitivity of nano
      surface-assisted (+)-mode LDI MS analyses.
AB  - A proton source employing a nanostructured gold surface for use in (+)-mode laser
      desorption ionization mass spectrometry (LDI-MS) was evaluated. Analysis of
      perdeuterated polyaromatic hydrocarbon compound dissolved in regular toluene,
      perdeuterated toluene, and deuterated methanol all showed that protonated ions
      were generated irregardless of solvent system. Therefore, it was concluded that
      residual water on the surface of the LDI plate was the major source of protons.
      The fact that residual water remaining after vacuum drying was the source of
      protons suggests that protons may be the limiting reagent in the LDI process and
      that overall ionization efficiency can be improved by incorporating an additional
      proton source. When extra proton sources, such as thiolate compounds and/or
      citric acid, were added to a nanostructured gold surface, the protonated signal
      abundance increased. These data show that protons are one of the limiting
      components in (+)-mode LDI MS analyses employing nanostructured gold surfaces.
      Therefore, it has been suggested that additional efforts are required to identify
      compounds that can act as proton donors without generating peaks that interfere
      with mass spectral interpretation. 

PMID- 23955003
TI  - PP2A regulatory subunit Balpha controls endothelial contractility and vessel
      lumen integrity via regulation of HDAC7.
AB  - To supply tissues with nutrients and oxygen, the cardiovascular system forms a
      seamless, hierarchically branched, network of lumenized tubes. Here, we show that
      maintenance of patent vessel lumens requires the Balpha regulatory subunit of
      protein phosphatase 2A (PP2A). Deficiency of Balpha in zebrafish precludes
      vascular lumen stabilization resulting in perfusion defects. Similarly,
      inactivation of PP2A-Balpha in cultured ECs induces tubulogenesis failure due to
      alteration of cytoskeleton dynamics, actomyosin contractility and maturation of
      cell-extracellular matrix (ECM) contacts. Mechanistically, we show that PP2A
      Balpha controls the activity of HDAC7, an essential transcriptional regulator of
      vascular stability. In the absence of PP2A-Balpha, transcriptional repression by
      HDAC7 is abrogated leading to enhanced expression of the cytoskeleton adaptor
      protein ArgBP2. ArgBP2 hyperactivates RhoA causing inadequate rearrangements of
      the EC actomyosin cytoskeleton. This study unravels the first specific role for a
      PP2A holoenzyme in development: the PP2A-Balpha/HDAC7/ArgBP2 axis maintains
      vascular lumens by balancing endothelial cytoskeletal dynamics and cell-matrix
      adhesion. 

PMID- 23955004
TI  - Immunity, inflammation, and bipolar disorder: diagnostic and therapeutic
      implications.
AB  - Bipolar disorder is now known to be associated not only with highly prevalent co
      occurring psychiatric and substance use disorders but also with medical
      comorbidities, such as cardiovascular diseases, diabetes mellitus, obesity and
      thyroid dysfunction. Inflammatory disturbances repeatedly observed in bipolar
      disorder, can explain some of the comorbidity between bipolar disorder and
      medical disorder. This revised perspective of bipolar disorders should promote
      the development of therapeutic tools. Immuno-inflammatory dysfunction may well
      represent a significant component of the underlying pathophysiology of the
      disorder. We therefore propose to review the immuno-inflammatory hypothesis in
      bipolar disorder considering the co-occurence with autoimmune diseases,
      immunological and inflammatory markers, as well as immuno-genetic markers which
      could lead to personalized treatments. 

PMID- 23955005
TI  - FeoC from Klebsiella pneumoniae contains a [4Fe-4S] cluster.
AB  - Iron is essential for pathogen survival, virulence, and colonization. Feo is
      suggested to function as the ferrous iron (Fe(2+)) transporter. The
      enterobacterial Feo system is composed of 3 proteins: FeoB is the indispensable
      component and is a large membrane protein likely to function as a permease; FeoA
      is a small Src homology 3 (SH3) domain protein that interacts with FeoB; FeoC is
      a winged-helix protein containing 4 conserved Cys residues in a sequence suitable
      for harboring a putative iron-sulfur (Fe-S) cluster. The presence of an iron
      sulfur cluster on FeoC has never been shown experimentally. We report that under
      anaerobic conditions, the recombinant Klebsiella pneumoniae FeoC (KpFeoC)
      exhibited hyperfine-shifted nuclear magnetic resonance (NMR) and a UV-visible (UV
      Vis) absorbance spectrum characteristic of a paramagnetic center. The electron
      paramagnetic resonance (EPR) and extended X-ray absorption fine structure (EXAFS)
      results were consistent only with the [4Fe-4S] clusters. Substituting the
      cysteinyl sulfur with oxygen resulted in significantly reduced cluster stability,
      establishing the roles of these cysteines as the ligands for the Fe-S cluster.
      When exposed to oxygen, the [4Fe-4S] cluster degraded to [3Fe-4S] and eventually
      disappeared. We propose that KpFeoC may regulate the function of the Feo
      transporter through the oxygen- or iron-sensitive coordination of the Fe-S
      cluster. 

PMID- 23955006
TI  - Acrylyl-coenzyme A reductase, an enzyme involved in the assimilation of 3
      hydroxypropionate by Rhodobacter sphaeroides.
AB  - The anoxygenic phototroph Rhodobacter sphaeroides uses 3-hydroxypropionate as a
      sole carbon source for growth. Previously, we showed that the gene (RSP_1434)
      known as acuI, which encodes a protein of the medium-chain
      dehydrogenase/reductase (MDR) superfamily, was involved in 3-hydroxypropionate
      assimilation via the reductive conversion to propionyl-coenzyme A (CoA). Based on
      these results, we speculated that acuI encoded acrylyl-CoA reductase. In this
      work, we characterize the in vitro enzyme activity of purified, recombinant AcuI
      using a coupled spectrophotometric assay. AcuI from R. sphaeroides catalyzes the
      NADPH-dependent acrylyl-CoA reduction to produce propionyl-CoA. Two other members
      of the MDR012 family within the MDR superfamily, the products of SPO_1914 from
      Ruegeria pomeroyi and yhdH from Escherichia coli, were shown to also be part of
      this new class of NADPH-dependent acrylyl-CoA reductases. The activities of the
      three enzymes were characterized by an extremely low Km for acrylyl-CoA (<3 MUM)
      and turnover numbers of 45 to 80 s(-1). These homodimeric enzymes were highly
      specific for NADPH (Km = 18 to 33 MUM), with catalytic efficiencies of more than
      10-fold higher for NADPH than for NADH. The introduction of codon-optimized
      SPO_1914 or yhdH into a DeltaacuI::kan mutant of R. sphaeroides on a plasmid
      complemented 3-hydroxypropionate-dependent growth. However, in their native
      hosts, SPO_1914 and yhdH are believed to function in the metabolism of substrates
      other than 3-hydroxypropionate, where acrylyl-CoA is an intermediate.
      Complementation of the DeltaacuI::kan mutant phenotype by crotonyl-CoA
      carboxylase/reductase from R. sphaeroides was attributed to the fact that the
      enzyme also uses acrylyl-CoA as a substrate. 

PMID- 23955007
TI  - The D3 bacteriophage alpha-polymerase inhibitor (Iap) peptide disrupts O-antigen
      biosynthesis through mimicry of the chain length regulator Wzz in Pseudomonas
      aeruginosa.
AB  - Lysogenic bacteriophage D3 causes seroconversion of Pseudomonas aeruginosa PAO1
      from serotype O5 to O16 by inverting the linkage between O-specific antigen (OSA)
      repeat units from alpha to beta. The OSA units are polymerized by Wzy to modal
      lengths regulated by Wzz1 and Wzz2. A key component of the D3 seroconversion
      machinery is the inhibitor of alpha-polymerase (Iap) peptide, which is able to
      solely suppress alpha-linked long-chain OSA production in P. aeruginosa PAO1. To
      establish the target specificity of Iap for Wzyalpha, changes in OSA phenotypes
      were examined via Western immunoblotting for wzz1 and wzz2 single-knockout
      strains, as well as a wzz1 wzz2 double knockout, following the expression of iap
      from a tuneable vector. Increased induction of Iap expression completely
      abrogated OSA production in the wzz1 wzz2 double mutant, while background levels
      of OSA production were still observed in either of the single mutants. Therefore,
      Iap inhibition of OSA biosynthesis was most effective in the absence of both Wzz
      proteins. Sequence alignment analyses revealed a high degree of similarity
      between Iap and the first transmembrane segment (TMS) of either Wzz1 or Wzz2.
      Various topology prediction analyses of the Iap sequence consistently predicted
      the presence of a single TMS, suggesting a propensity for Iap to insert itself
      into the inner membrane (IM). The compromised ability of Iap to abrogate Wzyalpha
      function in the presence of Wzz1 or Wzz2 provides compelling evidence that
      inhibition occurs after Wzyalpha inserts itself into the IM and is achieved
      through mimicry of the first TMS from the Wzz proteins of P. aeruginosa PAO1. 

PMID- 23955008
TI  - The characterization of a cyclic-di-GMP (c-Di-GMP) pathway leads to a new tool
      for studying c-Di-GMP metabolic genes.

PMID- 23955009
TI  - FeoA and FeoC are essential components of the Vibrio cholerae ferrous iron uptake
      system, and FeoC interacts with FeoB.
AB  - The ferrous iron transport system Feo is widely distributed among bacterial
      species, yet its physical structure and mechanism of iron transport are poorly
      understood. In Vibrio cholerae, the feo operon consists of three genes, feoABC.
      feoB encodes an 83-kDa protein with an amino-terminal GTPase domain and a carboxy
      terminal domain predicted to be embedded in the inner membrane. While FeoB is
      believed to form the pore for iron transport, the roles of FeoA and FeoC are
      unknown. In this work, we show that FeoA and FeoC, as well as the more highly
      conserved FeoB, are all required for iron acquisition by V. cholerae Feo. An in
      frame deletion of feoA, feoB, or feoC eliminated iron acquisition. The loss of
      transport activity in the feoA and feoC mutants was not due to reduced
      transcription of the feo operon, suggesting that these two small proteins are
      required for activity of the transporter. feoC was found to encode a protein that
      interacts with the cytoplasmic domain of FeoB, as determined using the BACTH
      bacterial two-hybrid system. Two conserved amino acids in FeoC were found to be
      necessary for the interaction with FeoB in the two-hybrid assay, and when either
      of these amino acids was mutated in the context of the entire feo operon, iron
      acquisition via Feo was reduced. No interaction of FeoA with FeoB or FeoC was
      detected in the BACTH two-hybrid assay. 

PMID- 23955011
TI  - Cheap and scalable synthesis of alpha-Fe2O3 multi-shelled hollow spheres as high
      performance anode materials for lithium ion batteries.
AB  - Delicate alpha-Fe2O3 multi-shelled hollow spheres have been prepared by a simple
      and scalable spray drying method followed by annealing in air. The resulting
      material shows high specific capacity, good cycling stability, and excellent rate
      performance in lithium ion battery applications. 

PMID- 23955010
TI  - Physiological and transcriptional responses to osmotic stress of two Pseudomonas
      syringae strains that differ in epiphytic fitness and osmotolerance.
AB  - The foliar pathogen Pseudomonas syringae is a useful model for understanding the
      role of stress adaptation in leaf colonization. We investigated the mechanistic
      basis of differences in the osmotolerance of two P. syringae strains, B728a and
      DC3000. Consistent with its higher survival rates following inoculation onto
      leaves, B728a exhibited superior osmotolerance over DC3000 and higher rates of
      uptake of plant-derived osmoprotective compounds. A global transcriptome analysis
      of B728a and DC3000 following an osmotic upshift demonstrated markedly distinct
      responses between the strains; B728a showed primarily upregulation of genes,
      including components of the type VI secretion system (T6SS) and alginate
      biosynthetic pathways, whereas DC3000 showed no change or repression of
      orthologous genes, including downregulation of the T3SS. DC3000 uniquely
      exhibited improved growth upon deletion of the biosynthetic genes for the
      compatible solute N-acetylglutaminylglutamine amide (NAGGN) in a minimal medium,
      due possibly to NAGGN synthesis depleting the cellular glutamine pool. Both
      strains showed osmoreduction of glnA1 expression, suggesting that decreased
      glutamine synthetase activity contributes to glutamate accumulation as a
      compatible solute, and both strains showed osmoinduction of 5 of 12 predicted
      hydrophilins. Collectively, our results demonstrate that the superior epiphytic
      competence of B728a is consistent with its strong osmotolerance, a proactive
      response to an osmotic upshift, osmoinduction of alginate synthesis and the T6SS,
      and resiliency of the T3SS to water limitation, suggesting sustained T3SS
      expression under the water-limited conditions encountered during leaf
      colonization. 

PMID- 23955012
TI  - Prevalence of subclinical mastitis in dairy farms in urban and peri-urban areas
      of Kampala, Uganda.
AB  - It is widely recognized that subclinical mastitis (SCM) is an extensive problem
      in the dairy industry worldwide. It is of particular concern in developing
      countries. The aim of this study was to establish the prevalence of SCM in dairy
      cattle in the urban and peri-urban areas of Kampala, Uganda and to gain
      information about pathogens and antibiotic resistance patterns. The study was
      conducted as a field study in 18 smallholder dairy farms in peri-urban Kampala,
      Uganda. All cows at the farms were physically examined, and cows with signs of
      clinical mastitis were excluded. Cows (n = 195) were tested with California
      Mastitis Test (CMT), and udder quarters with CMT score >=3 (scale 1-5) were milk
      sampled for bacteriological analysis. To allow further sub-analysis of the
      results, the stage of lactation, parity, milk production, production type, udder
      hygiene, and cow breed were recorded. Results indicate that 86.2 % (n = 168) of
      the tested cows had SCM in one or more quarters. The most common bacteriological
      outcome was infection with coagulase-negative staphylococci (54.7 %), followed by
      negative growth (24.9 %) and streptococci (16.2 %); all of which (n = 34) were
      sensitive to penicillin. Of the tested staphylococci (n = 17), the majority (58.9
      %) were positive for penicillinase production. Factors with significant impact on
      the prevalence of SCM at cow level were the stage of lactation, parity, and
      production type. The results suggest that the prevalence of SCM in Uganda is
      substantially higher than reported in previous studies and in other comparable
      developing countries. This implies that SCM deserves more attention and that
      improvement in dairy cow husbandry in terms of hygiene and management is
      necessary. 

PMID- 23955013
TI  - Effect of incorporation of thermo-regulatory genes into exotic layers on egg
      production and quality under tropical environment.
AB  - A breed development strategy aimed at making exotic layers (Lohmann Brown) more
      productive under tropical environment using thermo-regulatory genes is underway
      at Akate Farms in Kumasi, Ghana. The present experiment was carried out to find
      out the effect of the genes on egg production in hot and humid environments.
      Three genetic groups comprising naked-neck, frizzle and their normally feathered
      sibs were obtained after successive generations of crossing between naked-neck
      and frizzle cocks and Lohmann brown hens. A total of 270 18-week-old pullets, 90
      each of the 3 groups, were selected randomly and assigned to a completely
      randomized design experiment with 3 replicates, with 30 birds in each replicate
      group and kept up to a period of 72 weeks. The birds were kept in a partitioned
      open-sided deep-litter house constructed with sandcrete blocks with 30 pullets in
      each compartment. They were fed ad libitum with layer diets containing 18 % crude
      protein and 2,800 kcal ME/kg. Results obtained showed that the crossbred naked
      neck and frizzle phenotypes produced eggs at a significantly (P < 0.05) higher
      rates than their normally feathered sibs and also out-performed their normally
      feathered sibs in other egg production parameters measured, even though they all
      segregated from similar parents. This is an indication of the favourable effect
      of the genes on egg production under hot and humid environments. 

PMID- 23955014
TI  - First report of seroprevalence of swine influenza A virus in Tibetan pigs in
      Tibet, China.
AB  - Swine influenza A virus (SIV) is zoonotic pathogen that can be acquired by food
      borne transmission because food animals, for example pigs, are recognized as a
      reservoir. The objectives of this study were to determine the seroprevalence of
      anti-SIV (H1N1 and H3N2) in Tibetan pigs in Tibet Nationality Autonomous Region,
      China, a region with cold weather and high altitude. A total of 421 serum samples
      were randomly collected from Tibetan pigs in Tibet and were evaluated for
      antibodies against SIV using enzyme-linked immunosorbent assay. Overall, 52 %
      (219/421) of the animals was positive for H1N1, 16.9 % (71/421) positive for
      H3N2, and 8.8 % (37/421) positive for both H1N1 and H3N2. The results of the
      present survey indicated that SIV is highly prevalent among Tibetan pigs in
      Tibet, China. The results of the present investigation have implications for the
      ongoing control of SIV infection in Tibetan pigs in Tibet, China and elsewhere. 

PMID- 23955015
TI  - On the origins of human handedness and language: a comparative review of hand
      preferences for bimanual coordinated actions and gestural communication in
      nonhuman primates.
AB  - Within the evolutionary framework about the origin of human handedness and
      hemispheric specialization for language, the question of expression of population
      level manual biases in nonhuman primates and their potential continuities with
      humans remains controversial. Nevertheless, there is a growing body of evidence
      showing consistent population-level handedness particularly for complex manual
      behaviors in both monkeys and apes. In the present article, within a large
      comparative approach among primates, we will review our contribution to the field
      and the handedness literature related to two particular sophisticated manual
      behaviors regarding their potential and specific implications for the origins of
      hemispheric specialization in humans: bimanual coordinated actions and gestural
      communication. Whereas bimanual coordinated actions seem to elicit predominance
      of left-handedness in arboreal primates and of right-handedness in terrestrial
      primates, all handedness studies that have investigated gestural communication in
      several primate species have reported stronger degree of population-level right
      handedness compared to noncommunicative actions. Communicative gestures and
      bimanual actions seem to affect differently manual asymmetries in both human and
      nonhuman primates and to be related to different lateralized brain substrates. We
      will discuss (1) how the data of hand preferences for bimanual coordinated
      actions highlight the role of ecological factors in the evolution of handedness
      and provide additional support the postural origin theory of handedness proposed
      by MacNeilage [MacNeilage [2007]. Present status of the postural origins theory.
      In W. D. Hopkins (Ed.), The evolution of hemispheric specialization in primates
      (pp. 59-91). London: Elsevier/Academic Press] and (2) the hypothesis that the
      emergence of gestural communication might have affected lateralization in our
      ancestor and may constitute the precursors of the hemispheric specialization for
      language.

PMID- 23955017
TI  - Functional lengths of the lower limb arterial tree measured by CT angiography
      centreline analysis: implications for catheter lengths in peripheral angioplasty.
AB  - PURPOSE: Lower limb angioplasty is a common procedure. However, arterial lengths
      have not been well studied and there is no evidence base for the optimum catheter
      lengths required for the various applications of femoral or distal below-the-knee
      angioplasty. The industry standard catheter measures 80 cm. METHOD: Fifty CT
      angiograms were post-processed using vessel tracking and centreline analysis
      tools and lengths were measured from the ipsilateral first segment of the femoral
      artery (FSFA) (common femoral artery) to the contralateral FSFA and on to the
      second segment of the femoral artery (superficial femoral artery) and popliteal
      arteries down to the posterior tibial (PT) artery at the ankle. This allowed
      clinically meaningful lengths for 'cross-over' and 'antegrade' angioplasty to be
      calculated. RESULTS: Mean cross-over length to the second segment of the femoral
      artery as it crossed the femoral cortex was 72.3 cm, and the mean cross-over
      length to the popliteal artery at the knee joint was 83.8 cm, and the length from
      the FSFA to the PT was 85.1 cm. CONCLUSION: Selection of a standard length
      catheter can result in a situation where the catheter is too short. Optimum
      catheter length for a particular task will reduce the need for catheter exchanges
      and use of multiple balloons and therefore reduce complications, procedure time,
      radiation dose and cost.

PMID- 23955018
TI  - Granger causality--statistical analysis under a configural perspective.
AB  - The concept of Granger causality can be used to examine putative causal relations
      between two series of scores. Based on regression models, it is asked whether one
      series can be considered the cause for the second series. In this article, we
      propose extending the pool of methods available for testing hypotheses that are
      compatible with Granger causation by adopting a configural perspective. This
      perspective allows researchers to assume that effects exist for specific
      categories only or for specific sectors of the data space, but not for other
      categories or sectors. Configural Frequency Analysis (CFA) is proposed as the
      method of analysis from a configural perspective. CFA base models are derived for
      the exploratory analysis of Granger causation. These models are specified so that
      they parallel the regression models used for variable-oriented analysis of
      hypotheses of Granger causation. An example from the development of aggression in
      adolescence is used. The example shows that only one pattern of change in
      aggressive impulses over time Granger-causes change in physical aggression
      against peers. 

PMID- 23955019
TI  - Electrochemical biosensor for quantitation of anti-DNA autoantibodies in human
      serum.
AB  - Measurement of serum autoantibody is a critical tool in the diagnosis and
      management of autoimmune diseases. However, rapid and convenient methods at the
      point-of care have not been achieved in large part because any one antibody
      species is a heterogeneous and miniscule fraction of the total serum
      immunoglobulin displaying identical properties other than its antigen-binding
      specificity. The present system addresses these challenges by vacuum-mediated
      transport of diluted serum through an antigen-coated porous membrane. To measure
      anti-DNA autoantibodies, native DNA was immobilized into a poly(vinylidene
      fluoride) membrane pre-coated with a synthetic phenylalanine/lysine co-polymer.
      Flow-through of primary and peroxidase-conjugated secondary antibodies over the
      course of 3 min enhanced productive antibody-antigen interactions by bringing the
      reactants into close mutual proximity. Signal was quantified electrochemically
      during the enzymatic conversion of the tetramethylbenzidine substrate to a charge
      transfer complex. The electrochemical signals generated by sera from patients
      with systemic lupus erythematosus using this device showed good quantitative
      correlation with a standard enzyme-linked immunosorbent assay and displayed
      similar detection limits. Inter- and intra-assay variability and electrode
      uniformity were favorable as was a two-month test of the stability of the DNA
      coated membrane. While refining the fluidics requirements of this biosensor will
      be needed, its capacity to quantify over the course of 30 min anti-DNA antibodies
      in fresh human serum without background reactivity of normal serum makes this a
      promising technology as a point-of care device of clinical utility.

PMID- 23955016
TI  - Pathologies at the nexus of blood coagulation and inflammation: thrombin in
      hemostasis, cancer, and beyond.
AB  - Thrombin is the protease involved in blood coagulation. Its deregulation can lead
      to hemostatic abnormalities, which range from subtle subclinical to serious life
      threatening coagulopathies, i.e., during septicemia. Additionally, thrombin plays
      important roles in many (patho)physiological conditions that reach far beyond its
      well-established role in stemming blood loss and thrombosis, including embryonic
      development and angiogenesis but also extending to inflammatory processes,
      complement activation, and even tumor biology. In this review, we will address
      thrombin's broad roles in diverse (patho)physiological processes in an
      integrative way. We will also discuss thrombin as an emerging major target for
      novel therapies. 

PMID- 23955020
TI  - Porcine bone grafts defatted by lipase: efficacy of defatting and assessment of
      cytocompatibility.
AB  - Defatting is an important procedure for the preparation of bone grafts because
      lipids in bone grafts strongly influence the osteointegration. Lipases have been
      widely used in different fields. However, study on the application to defatting
      process for bone grafts preparation has never been found so far. In this study,
      bone samples were treated respectively by lipase, NaHCO(3)/Na(2)CO(3), acetone
      and deionized water. The lipids content of processed bone grafts was calculated
      in Soxhlet extractor method. Surface morphology of the bone grafts was observed
      under scanning electron microscope (SEM). DNA content of processed bone grafts
      was measured. Cytocompatibility was evaluated by co-culturing mouse
      preosteoblasts (MC3T3-E1) on defatted bone cubes. Proliferation rates of MC3T3-E1
      were examined by cell counting kit-8 (CCK-8) assay. No statistically significant
      difference was found between lipids amount of bone processed by lipase (0.46 +/-
      0.16 %) and acetone (1.11 +/- 0.13 %) (P > 0.05). Both of them were significantly
      lower than that in groups processed by Na(2)CO(3)/NaHCO(3) (3.46 +/- 0.69 %) and
      deionized water (8.88 +/- 0.18 %) (P = 0.000). Only cell debris were discovered
      over the surface of bone processed by lipase or acetone, while lipid droplets
      were observed on bone processed by Na(2)CO(3)/NaHCO(3) or water by SEM. The
      difference of DNA concentration between the bone processed by lipase (3.16 +/-
      0.81 ng/MUl) and acetone (4.14 +/- 0.40 ng/MUl) is not statistically significant
      (P > 0.05). Both of them are significantly lower than that groups processed by
      Na(2)CO(3)/NaHCO(3) (5.22 +/- 0.38 ng/MUl) and water (7.88 +/- 0.55 ng/MUl) (P <
      0.05). MC3T3-E1 cells maintained their characteristic spreading on the trabecular
      surfaces of bone processed by lipase. There were no statistically significant
      differences among absorbance of lipase, acetone groups in CCK-8 assay. The
      application of lipase to bone tissue defatting appears to be a very promising
      technique for bone grafts preparation.

PMID- 23955021
TI  - Allyl isothiocyanate sensitizes TRPV1 to heat stimulation.
AB  - The powerful plant-derived irritant allyl isothiocyanate (AITC, aka mustard oil)
      induces hyperalgesia to heat in rodents and humans through mechanisms that are
      not yet fully understood. It is generally believed that AITC activates the
      broadly tuned chemosensory cation channel transient receptor potential cation
      channel subfamily A member 1 (TRPA1), triggering an inflammatory response that
      sensitizes the heat sensor transient receptor potential cation channel subfamily
      V member 1 (TRPV1). In the view of recent data demonstrating that AITC can
      directly activate TRPV1, we here explored the possibility that this compound
      sensitizes TRPV1 to heat stimulation in a TRPA1-independent manner. Patch-clamp
      recordings and intracellular Ca(2+) imaging experiments in HEK293T cells over
      expressing mouse TRPV1 revealed that the increase in channel activation induced
      by heating is larger in the presence of AITC than in control conditions. The
      analysis of the effects of AITC and heat on the current-voltage relationship of
      TRPV1 indicates that the mechanism of sensitization is based on additive shifts
      of the voltage dependence of activation towards negative voltages. Finally,
      intracellular Ca(2+) imaging experiments in mouse sensory neurons isolated from
      Trpa1 KO mice yielded that AITC enhances the response to heat, specifically in
      the subpopulation expressing TRPV1. Furthermore, this effect was strongly reduced
      by the TRPV1 inhibitor capsazepine and virtually absent in neurons isolated from
      double Trpa1/Trpv1 KO mice. Taken together, these findings demonstrate that TRPV1
      is a locus for cross sensitization between AITC and heat in sensory neurons and
      may help explaining, at least in part, the role of this channel in AITC-induced
      hyperalgesia to heat. 

PMID- 23955022
TI  - E2 ubiquitin-conjugating enzymes regulate the deubiquitinating activity of OTUB1.
AB  - OTUB1 is a Lys48-specific deubiquitinating enzyme that forms a complex in vivo
      with E2 ubiquitin (Ub)-conjugating enzymes including UBC13 and UBCH5. OTUB1 binds
      E2~Ub thioester intermediates and prevents ubiquitin transfer, thereby
      noncatalytically inhibiting accumulation of polyubiquitin. We report here that a
      second role of OTUB1-E2 interactions is to stimulate OTUB1 cleavage of Lys48
      polyubiquitin. This stimulation is regulated by the ratio of charged to uncharged
      E2 and by the concentration of Lys48-linked polyubiquitin and free ubiquitin.
      Structural and biochemical studies of human and worm OTUB1 and UBCH5B show that
      the E2 enzyme stimulates binding of the Lys48 polyubiquitin substrate by
      stabilizing folding of the OTUB1 N-terminal ubiquitin-binding helix. Our results
      suggest that OTUB1-E2 complexes in the cell are poised to regulate polyubiquitin
      chain elongation or degradation in response to changing levels of E2 charging and
      available free ubiquitin. 

PMID- 23955023
TI  - Defining the structural relationship between kainate-receptor deactivation and
      desensitization.
AB  - Desensitization is an important mechanism curtailing the activity of ligand-gated
      ion channels (LGICs). Although the structural basis of desensitization is not
      fully resolved, it is thought to be governed by physicochemical properties of
      bound ligands. Here, we show the importance of an allosteric cation-binding
      pocket in controlling transitions between activated and desensitized states of
      rat kainate-type (KAR) ionotropic glutamate receptors (iGluRs). Tethering a
      positive charge to this pocket sustains KAR activation, preventing
      desensitization, whereas mutations that disrupt cation binding eliminate channel
      gating. These different outcomes explain the structural distinction between
      deactivation and desensitization. Deactivation occurs when the ligand unbinds
      before the cation, whereas desensitization proceeds if a ligand is bound without
      cation pocket occupancy. This sequence of events is absent from AMPA-type iGluRs;
      thus, cations are identified as gatekeepers of KAR gating, a role unique among
      even closely related LGICs. 

PMID- 23955024
TI  - "You need something like this to give you guidelines on what to do": patients'
      and partners' use and perceptions of a self-directed coping skills training
      resource.
AB  - PURPOSE: This study aims to report on the acceptability of a self-directed coping
      skills intervention, called Coping-Together, for patients affected by cancer and
      their partners, including the strengths and limitations of the intervention
      design. METHODS: This initial version of Coping-Together included a series of
      four booklets, which aimed to provide practical coping strategies for the day-to
      day management of common physical and psychosocial challenges. Thirty semi
      structured interviews were conducted with 27 patients and/or 14 partners.
      Interviews were audiorecorded, transcribed verbatim, and analyzed for content.
      RESULTS: Participants endorsed the self-directed format, and the focus of Coping
      Together on practical information was a feature that set it apart from other
      resources. The majority of participants interviewed felt that the proposed coping
      strategies were "doable"; however, only half of the participants reported
      learning new coping skills after reading the booklets. Additional benefits of
      reading the booklets were increasing awareness of challenges to prepare for,
      giving hope that something can help you "pull through", providing a sense of
      normality, connecting patients and partners to people and services, and
      complementing support received from health professionals. Despite the general
      acceptability of the intervention, some aspects of its design were criticized,
      including the workbook-like exercises, expectations about using the resource
      together, level of guidance provided, and amount of information included. In
      general, most participants felt that too much negative information was included,
      whereas more experiential information was desired. CONCLUSIONS: Preliminary
      evaluation of Coping-Together supported its practical approach and highlighted
      improvements to enhance its contribution to patient and partner coping.

PMID- 23955025
TI  - Evidence is in the eye of the beholder.

PMID- 23955027
TI  - Dogs' comprehension of referential emotional expressions: familiar people and
      familiar emotions are easier.
AB  - Dogs have been shown to discriminate between human facial expressions, and they
      seem to use human emotional communication to regulate their behaviour towards an
      external object/situation. However, it is still not clear (1) whether they just
      respond to the emotional message received with a corresponding increase/decrease
      in their level of activation or whether they perceive that the emotional message
      refers to a specific object, (2) which emotional message they use to modify their
      behaviour (i.e. whether they are following the positive message or avoiding the
      negative one) and (3) whether their familiarity with the informant has an effect
      on the dogs' behaviour. To address these issues, five groups of dogs were tested
      in two experiments. The first group observed the owner delivering two different
      emotional messages (happiness and fear) towards two identical objects hidden
      behind barriers, and the second group observed the owner delivering the same
      emotional messages but with no-objects present in the room. The third and the
      fourth groups observed the owner delivering a happy versus a neutral, and a
      negative versus a neutral emotional message towards the hidden objects. Finally,
      the fifth group observed a stranger acting like the owner of the first group.
      When the owner was acting as the informant, dogs seemed to be capable of
      distinguishing between a fearful and happy emotional expression and
      preferentially chose to investigate a box eliciting an expression of happiness
      rather than of fear or neutrality. Dogs, however, seemed to have greater
      difficulty in distinguishing between the fearful and neutral emotional messages
      delivered by the owner and between the happy and fearful expressions delivered by
      the stranger. Results suggest that dogs have learned to associate their owners'
      positive emotional messages to positive outcomes, and hence use their
      communicative messages to guide their actions. However, negative emotional
      messages and those delivered by strangers are not as clear to dogs. 

PMID- 23955026
TI  - Burden among partner caregivers of patients diagnosed with localized prostate
      cancer within 1 year after diagnosis: an economic perspective.
AB  - PURPOSE: Informal care plays an important role in the overall care for people
      with cancer. This study estimates lost productivity and informal caregiving and
      associated costs among partner caregivers of localized prostate cancer patients
      within 1 year after diagnosis. METHODS: We applied data from the Family and
      Cancer Therapy Selection study, a three-wave self-administered survey among
      patients diagnosed with localized prostate cancer and their partner caregivers in
      multiple clinics in the USA. Time spent was measured by the sum of working hours
      lost, informal caregiving hours performed, and hours spent on household chores.
      The national median income for women 55 years or older was used to calculate
      costs associated with the time spent using the opportunity cost method.
      Descriptive and bivariate analyses were conducted. RESULTS: The average working
      hours decreased from 14.0 h/week (SD = 17.6) to 10.9 h/week (SD = 15.9), without
      a significant change in responsibility/intensity at work. The mean annual time
      spent on informal caregiving and household chores was 65.9 h/year (SD = 172.4)
      and 76.2 h/year (SD = 193.3), respectively. The mean annual economic burden among
      partner caregivers was US$6,063 (range US$571-US$47,105) in 2009 dollars
      accounted for by a mean of 276.2 h (range 26-2,146) in the study sample. The time
      spent on informal caregiving and household chores varied by patient and caregiver
      characteristics. CONCLUSIONS: Pilot estimates on non-medical economic burden
      among partner caregivers (spouses) during the initial phase of the treatment
      provide important information for comprehensive estimation of disease burden and
      can be used in cost-effectiveness analyses of prostate cancer interventions.

PMID- 23955028
TI  - Learning and memory in the Port Jackson shark, Heterodontus portusjacksoni.
AB  - Basic understanding of the fundamental principles and mechanisms involved in
      learning is lacking for elasmobranch fishes. Our aim in this study was to
      experimentally investigate the learning and memory capacity of juvenile Port
      Jackson sharks, Heterodontus portusjacksoni. Sharks (N = 30) were conditioned
      over a 19-day period to associate an underwater LED light or stream of air
      bubbles [conditioned stimulus (CS)] with a food reward [unconditioned stimulus
      (US)], using three procedures (delay, trace and control). During experiments, the
      CS signalled at a random time between 180 and 300 s for 30 s (six times per day).
      For the delay the US overlapped in time with the CS, for the trace the US
      delivered 10 s after the CS and for our control the US was delivered at random
      time between 180 and 300 s after the CS. H. portusjacksoni sharks trained in all
      procedures improved consistently in their time to obtain food, indicative of
      Pavlovian learning. Importantly, the number of sharks in the feeding area 5 s
      prior to CS onset did not change over time for any procedures. However,
      significantly more sharks were present 5 s after CS onset for delay for both air
      bubble and light CS. Sharks trained in the delay and trace procedures using air
      bubbles as the CS also displayed significantly more anticipatory behaviours, such
      as turning towards the CS and biting. Sharks trained with the light CS did not
      exhibit such behaviours; however, trace procedural sharks did show a significant
      improvement in moving towards the CS at its onset. At 20 and 40 days after the
      end of the conditioning experiments, some sharks were presented the CS without
      reward. Two sharks trained in the delay procedure using air-bubbles as the CS
      exhibited biting behaviours: one at 20 and the other at 40 days. This study
      demonstrates that H. portusjacksoni have the capacity to learn a classical
      conditioning procedure relatively quickly (30 trials during 5 days) and associate
      two time-separated events and retention of learnt associations for at least 24 h
      and possibly up to 40 days. 

PMID- 23955029
TI  - The Materials Science beamline upgrade at the Swiss Light Source.
AB  - The Materials Science beamline at the Swiss Light Source has been operational
      since 2001. In late 2010, the original wiggler source was replaced with a novel
      insertion device, which allows unprecedented access to high photon energies from
      an undulator installed in a medium-energy storage ring. In order to best exploit
      the increased brilliance of this new source, the entire front-end and optics had
      to be redesigned. In this work, the upgrade of the beamline is described in
      detail. The tone is didactic, from which it is hoped the reader can adapt the
      concepts and ideas to his or her needs. 

PMID- 23955030
TI  - Energy calibration issues in nuclear resonant vibrational spectroscopy: observing
      small spectral shifts and making fast calibrations.
AB  - The conventional energy calibration for nuclear resonant vibrational spectroscopy
      (NRVS) is usually long. Meanwhile, taking NRVS samples out of the cryostat
      increases the chance of sample damage, which makes it impossible to carry out an
      energy calibration during one NRVS measurement. In this study, by manipulating
      the 14.4 keV beam through the main measurement chamber without moving out the
      NRVS sample, two alternative calibration procedures have been proposed and
      established: (i) an in situ calibration procedure, which measures the main NRVS
      sample at stage A and the calibration sample at stage B simultaneously, and
      calibrates the energies for observing extremely small spectral shifts; for
      example, the 0.3 meV energy shift between the 100%-(57)Fe-enriched [Fe4S4Cl4](=)
      and 10%-(57)Fe and 90%-(54)Fe labeled [Fe4S4Cl4](=) has been well resolved; (ii)
      a quick-switching energy calibration procedure, which reduces each calibration
      time from 3-4 h to about 30 min. Although the quick-switching calibration is not
      in situ, it is suitable for normal NRVS measurements.

PMID- 23955031
TI  - Periodically structured X-ray waveguides.
AB  - The properties of X-ray vacuum-gap waveguides (WGs) with additional periodic
      structure on one of the reflecting walls are studied. Theoretical considerations,
      numerical simulations and experimental results confirm that the periodic
      structure imposes additional conditions on efficient propagation of the
      electromagnetic field along the WGs. The transmission is maximum for guided modes
      that possess sufficient phase synchronism with the periodic structure (here
      called 'super-resonances'). The field inside the WGs is essentially given at low
      incidence angle by the fundamental mode strongly coupled with the corresponding
      phased-matched mode. Both the simulated and the experimental diffraction patterns
      show in the far field that propagation takes place essentially only for low
      incidence angles, confirming the mode filtering properties of the structured X
      ray waveguides.

PMID- 23955032
TI  - Current saturation in free-air ionization chambers with chopped synchrotron
      radiation.
AB  - Saturation curves for free-air ionization chambers with electrode gap widths of
      4.2, 8.4 and 18 mm were obtained for 10 and 15 keV undulator synchrotron
      radiation thinned with a 230 Hz rotating-disk chopper. Ion recombination in free
      air ionization chambers was found to be inversely proportional to the applied
      electric field, and an expression that satisfactorily reproduced the ion
      recombination rate is determined. A comparison of the expressions for continuous
      and pulsed X-rays revealed that chopped high-intensity X-rays require a higher
      voltage to attain saturation when the product of the pulse width and electric
      field exceeds a value that depends on the X-ray energy. This behaviour was
      observed explicitly for 10 keV X-rays in measurements with the ionization chamber
      placed before and after the chopper.

PMID- 23955033
TI  - Local study of fissure caries by Fourier transform infrared microscopy and X-ray
      diffraction using synchrotron radiation.
AB  - Investigations of intact dental enamel as well as carious-affected human dental
      enamel were performed using infrared spectromicroscopy and X-ray diffraction
      applying synchrotron radiation. Caries of enamel was shown to be characterized by
      an increase in the number of deformation and valence vibrations for N-C-O, N-H
      and C=O bonds, a decrease of the crystallinity index, and by the absence of the
      preferable orientation of hydroxyapatite crystals within the affected enamel.
      This indicates the presence of destructive processes in the organic matrix of
      hard tooth tissues. 

PMID- 23955034
TI  - Single-crystal diffraction at the Extreme Conditions beamline P02.2: procedure
      for collecting and analyzing high-pressure single-crystal data.
AB  - Fast detectors employed at third-generation synchrotrons have reduced collection
      times significantly and require the optimization of commercial as well as
      customized software packages for data reduction and analysis. In this paper a
      procedure to collect, process and analyze single-crystal data sets collected at
      high pressure at the Extreme Conditions beamline (P02.2) at PETRA III, DESY, is
      presented. A new data image format called 'Esperanto' is introduced that is
      supported by the commercial software package CrysAlis(Pro) (Agilent Technologies
      UK Ltd). The new format acts as a vehicle to transform the most common area
      detector data formats via a translator software. Such a conversion tool has been
      developed and converts tiff data collected on a Perkin Elmer detector, as well as
      data collected on a MAR345/555, to be imported into the CrysAlis(Pro) software.
      In order to demonstrate the validity of the new approach, a complete structure
      refinement of boron-mullite (Al5BO9) collected at a pressure of 19.4 (2) GPa is
      presented. Details pertaining to the data collections and refinements of B
      mullite are presented.

PMID- 23955035
TI  - Determination of nanostructure of liposomes containing two model drugs by X-ray
      scattering from a synchrotron source.
AB  - Small-angle X-ray scattering has been employed to study how the introduction of
      paracetamol and acetylsalicylic acid into a liposome bilayer system affects the
      system's nanostructure. An X-ray scattering model, developed for multilamellar
      liposome systems [Pabst et al. (2000), Phys. Rev. E, 62, 4000-4009], has been
      used to fit the experimental data and to extract information on how structural
      parameters, such as the number and thickness of the bilayers of the liposomes,
      thickness of the water layer in between the bilayers, size and volume of the head
      and tail groups, are affected by the drugs and their concentration. Even though
      the experimental data reveal a complicated picture of the drug-bilayer
      interaction, they clearly show a correlation between nanostructure, drug and
      concentration in some aspects. The localization of the drugs in the bilayers is
      discussed.

PMID- 23955036
TI  - Using a standard sample to estimate the X-ray wavelength of the 1W2A SAXS
      beamline at BSRF.
AB  - This contribution describes a method for measuring diffraction peaks of a
      standard sample to estimate the incident X-ray wavelength at the 1W2A SAXS
      beamline at BSRF. A simple simulation has been performed to establish the factors
      influencing the accuracy of the wavelength measurement. Appropriate measurement
      conditions and error control measures are presented. An actual experimental
      example further verifies the effectiveness of the simulation. This method is
      particularly suitable for synchrotron radiation beamlines using bent triangular
      crystal monochromators.

PMID- 23955037
TI  - Magnesium K-edge XANES spectroscopy of geological standards.
AB  - Magnesium K-edge X-ray absorption near-edge structure (XANES) spectra have been
      investigated to develop a systematic understanding of a suite of Mg-bearing
      geological materials such as silicate and carbonate minerals, sediments, rocks
      and chemical reagents. For the model compounds the Mg XANES was found to vary
      widely between compounds and to provide a fingerprint for the form of Mg involved
      in geologic materials. The energy positions and resonance features obtained from
      these spectra can be used to specify the dominant molecular host site of Mg, thus
      shedding light on Mg partitioning and isotope fractionation in geologic materials
      and providing a valuable complement to existing knowledge of Mg geochemistry. 

PMID- 23955038
TI  - Characteristics of X-ray attenuation in electrospun bismuth oxide/polylactic acid
      nanofibre mats.
AB  - The characteristics of the X-ray attenuation in electrospun nano(n)- and micro(m)
      Bi2O3/polylactic acid (PLA) nanofibre mats with different Bi2O3 loadings were
      compared as a function of energy using mammography (i.e. tube voltages of 22-49
      kV) and X-ray absorption spectroscopy (XAS) (7-20 keV). Results indicate that X
      ray attenuation by electrospun n-Bi2O3/PLA nanofibre mats is distinctly higher
      than that of m-Bi2O3/PLA nanofibre mats at all energies investigated. In
      addition, with increasing filler loading (n-Bi2O3 or m-Bi2O3), the porosity of
      the nanofibre mats decreased, thus increasing the X-ray attenuation, except for
      the sample containing 38 wt% Bi2O3 (the highest loading in the present study).
      The latter showed higher porosity, with some beads formed, thus resulting in a
      sudden decrease in the X-ray attenuation.

PMID- 23955039
TI  - X-ray dynamical diffraction Fraunhofer holography.
AB  - An X-ray dynamical diffraction Fraunhofer holographic scheme is proposed.
      Theoretically it is shown that the reconstruction of the object image by visible
      light is possible. The spatial and temporal coherence requirements of the
      incident X-ray beam are considered. As an example, the hologram recording as well
      as the reconstruction by visible light of an absolutely absorbing wire are
      discussed.

PMID- 23955040
TI  - Assessment of the serotonin pathway as a therapeutic target for pulmonary
      hypertension.
AB  - Blockade of the serotonin reuptake transporter (5-HTT), using fluoxetine, has
      been identified as a potential therapeutic target for preventing and,
      importantly, reversing pulmonary hypertension (PH). This study utilized
      synchrotron radiation microangiography to determine whether fluoxetine could
      prevent or reverse endothelial dysfunction and vessel rarefaction, which underpin
      PH. PH was induced by a single injection of monocrotaline (MCT; 60 mg kg(-1)).
      Following MCT administration, rats received daily injections of either saline or
      fluoxetine (MCT+Fluox; 10 mg kg(-1)) for three weeks. A third group of rats also
      received the fluoxetine regime, but only three weeks after MCT (MCT+FluoxDelay).
      Control rats received daily injections of saline. Pulmonary microangiography was
      performed to assess vessel branching density and visualize dynamic changes in
      vessel diameter following (i) acute fluoxetine or (ii) acetylcholine, sodium
      nitroprusside, BQ-123 (ET-1A receptor blocker) and L-NAME (NOS inhibitor).
      Monocrotaline induced PH that was inevitably terminal. 'Delayed' treatment of
      fluoxetine (MCT+FluoxDelay) was unable to reverse the progression of PH. Early
      fluoxetine treatment pre-PH (i.e. MCT+Fluox) attenuated but did not completely
      prevent vascular remodeling, vessel rarefaction and an increase in pulmonary
      pressure, and it did not prevent pulmonary endothelial dysfunction.
      Interestingly, fluoxetine treatment did counter-intuitively prevent the onset of
      right ventricular hypertrophy. Using synchrotron radiation microangiography,
      selective blockade of the serotonin reuptake transporter alone is highlighted as
      not being sufficient to prevent pulmonary endothelial dysfunction, which is the
      primary instigator for the inevitable onset of vascular remodeling and vessel
      rarefaction. Accordingly, potential therapeutic strategies should aim to target
      multiple pathways to ensure an optimal outcome.

PMID- 23955041
TI  - A new on-axis micro-spectrophotometer for combining Raman, fluorescence and
      UV/Vis absorption spectroscopy with macromolecular crystallography at the Swiss
      Light Source.
AB  - The combination of X-ray diffraction experiments with optical methods such as
      Raman, UV/Vis absorption and fluorescence spectroscopy greatly enhances and
      complements the specificity of the obtained information. The upgraded version of
      the in situ on-axis micro-spectrophotometer, MS2, at the macromolecular
      crystallography beamline X10SA of the Swiss Light Source is presented. The
      instrument newly supports Raman and resonance Raman spectroscopy, in addition to
      the previously available UV/Vis absorption and fluorescence modes. With the
      recent upgrades of the spectral bandwidth, instrument stability, detection
      efficiency and control software, the application range of the instrument and its
      ease of operation were greatly improved. Its on-axis geometry with collinear X
      ray and optical axes to ensure optimal control of the overlap of sample volumes
      probed by each technique is still unique amongst comparable facilities worldwide
      and the instrument has now been in general user operation for over two years.

PMID- 23955042
TI  - Synergistic effect of cisplatin and synchrotron irradiation on F98 gliomas
      growing in nude mice.
AB  - Among brain tumors, glioblastoma multiforme appears as one of the most aggressive
      forms of cancer with poor prognosis and no curative treatment available.
      Recently, a new kind of radio-chemotherapy has been developed using synchrotron
      irradiation for the photoactivation of molecules with high-Z elements such as
      cisplatin (PAT-Plat). This protocol showed a cure of 33% of rats bearing the F98
      glioma but the efficiency of the treatment was only measured in terms of overall
      survival. Here, characterization of the effects of the PAT-Plat on tumor volume
      and tumor blood perfusion are proposed. Changes in these parameters may predict
      the overall survival. Firstly, changes in tumor growth of the F98 glioma
      implanted in the hindlimb of nude mice after the PAT-Plat treatment and its
      different modalities have been characterized. Secondly, the effects of the
      treatment on tumor blood perfusion have been observed by intravital two-photon
      microscopy. Cisplatin alone had no detectable effect on the tumor volume. A
      reduction of tumor growth was measured after a 15 Gy synchrotron irradiation, but
      the whole therapy (15 Gy irradiation + cisplatin) showed the largest decrease in
      tumor growth, indicating a synergistic effect of both synchrotron irradiation and
      cisplatin treatment. A high number of unperfused vessels (52%) were observed in
      the peritumoral area in comparison with untreated controls. In the PAT-Plat
      protocol the transient tumor growth reduction may be due to synergistic
      interactions of tumor-cell-killing effects and reduction of the tumor blood
      perfusion.

PMID- 23955043
TI  - An efficient numerical tool for dose deposition prediction applied to synchrotron
      medical imaging and radiation therapy.
AB  - Medical imaging and radiation therapy are widely used synchrotron-based
      techniques which have one thing in common: a significant dose delivery to
      typically biological samples. Among the ways to provide the experimenters with
      image guidance techniques indicating optimization strategies, Monte Carlo
      simulation has become the gold standard for accurately predicting radiation dose
      levels under specific irradiation conditions. A highly important hampering factor
      of this method is, however, its slow statistical convergence. A track length
      estimator (TLE) module has been coded and implemented for the first time in the
      open-source Monte Carlo code GATE/Geant4. Results obtained with the module and
      the procedures used to validate them are presented. A database of energy
      absorption coefficients was also generated, which is used by the TLE calculations
      and is now also included in GATE/Geant4. The validation was carried out by
      comparing the TLE-simulated doses with experimental data in a synchrotron
      radiation computed tomography experiment. The TLE technique shows good agreement
      versus both experimental measurements and the results of a classical Monte Carlo
      simulation. Compared with the latter, it is possible to reach a pre-defined
      statistical uncertainty in about two to three orders of magnitude less time for
      complex geometries without loss of accuracy. 

PMID- 23955044
TI  - Three-dimensional phase-contrast X-ray microtomography with scanning-imaging X
      ray microscope optics.
AB  - A three-dimensional (3D) X-ray tomographic micro-imaging system has been
      developed. The optical system is based on a scanning-imaging X-ray microscope
      (SIXM) optics, which is a hybrid system consisting of a scanning microscope
      optics with a one-dimensional (1D) focusing (line-focusing) device and an imaging
      microscope optics with a 1D objective. In the SIXM system, each 1D dataset of a
      two-dimensional (2D) image is recorded independently. An object is illuminated
      with a line-focused beam. Positional information of the region illuminated by the
      line-focused beam is recorded with the 1D imaging microscope optics as line
      profile data. By scanning the object with the line focus, 2D image data are
      obtained. In the same manner as for a scanning microscope optics with a multi
      pixel detector, imaging modes such as phase contrast and absorption contrast can
      be arbitrarily configured after the image data acquisition. By combining a
      tomographic scan method and the SIXM system, quantitative 3D imaging is
      performed. Results of a feasibility study of the SIXM for 3D imaging are shown.

PMID- 23955045
TI  - Combined measurement of X-ray photon correlation spectroscopy and diffracted X
      ray tracking using pink beam X-rays.
AB  - Combined X-ray photon correlation spectroscopy (XPCS) and diffracted X-ray
      tracking (DXT) measurements of carbon-black nanocrystals embedded in styrene
      butadiene rubber were performed. From the intensity fluctuation of speckle
      patterns in a small-angle scattering region (XPCS), dynamical information
      relating to the translational motion can be obtained, and the rotational motion
      is observed through the changes in the positions of DXT diffraction spots.
      Graphitized carbon-black nanocrystals in unvulcanized styrene-butadiene rubber
      showed an apparent discrepancy between their translational and rotational
      motions; this result seems to support a stress-relaxation model for the origin of
      super-diffusive particle motion that is widely observed in nanocolloidal systems.
      Combined measurements using these two techniques will give new insights into
      nanoscopic dynamics, and will be useful as a microrheology technique.

PMID- 23955046
TI  - Acoustic methods for high-throughput protein crystal mounting at next-generation
      macromolecular crystallographic beamlines.
AB  - To take full advantage of advanced data collection techniques and high beam flux
      at next-generation macromolecular crystallography beamlines, rapid and reliable
      methods will be needed to mount and align many samples per second. One approach
      is to use an acoustic ejector to eject crystal-containing droplets onto a solid X
      ray transparent surface, which can then be positioned and rotated for data
      collection. Proof-of-concept experiments were conducted at the National
      Synchrotron Light Source on thermolysin crystals acoustically ejected onto a
      polyimide 'conveyor belt'. Small wedges of data were collected on each crystal,
      and a complete dataset was assembled from a well diffracting subset of these
      crystals. Future developments and implementation will focus on achieving ejection
      and translation of single droplets at a rate of over one hundred per second.

PMID- 23955047
TI  - White-beam X-ray radioscopy and tomography with simultaneous diffraction at the
      EDDI beamline.
AB  - A set-up for simultaneous imaging and diffraction that yields radiograms with up
      to 200 frames per second and 5.6 um effective pixel size is presented. Tomograms
      and diffractograms are acquired together in 10 s. Two examples illustrate the
      attractiveness of combining these methods at the EDDI beamline for in situ
      studies.

PMID- 23955048
TI  - Fifty years since the first European synchrotron-radiation-derived XAFS spectrum
      (Frascati, 1963).
AB  - The first absorption spectra recorded in Europe using synchrotron radiation as
      the X-ray source were the K-edge of Al and the LIII-edge of Cu taken at Frascati
      electron synchrotron in May 1963 by the French-Italian group comprised of Y.
      Cauchois, C. Bonnelle and G. Missoni.

PMID- 23955050
TI  - England ends the ban on healthcare workers with HIV performing certain
      procedures.

PMID- 23955051
TI  - Study finds that half of Indian households affected by cancer have to sell assets
      to fund care.

PMID- 23955052
TI  - Radioprotective effect of epicatechin in cultured human fibroblasts and
      zebrafish.
AB  - Radiation-induced normal cell damage limits the delivery of high-dose radiation
      to targeted cancer. This study investigated the effect of epicatechin (EC), a
      minor component of green tea extracts, on radiation-induced cellular damage in
      vitro in primary cultured human fibroblasts and in vivo in a zebrafish model.
      Cell viability, proliferation and wound-healing efficacy, mitochondrial membrane
      potential, and reactive oxygen species (ROS) generation as well as changes in the
      signaling pathway related to apoptosis were investigated in fibroblasts. The
      therapeutic effects of EC were explored in a zebrafish model. EC increased
      clonogenic survival and restored the migration ability of the fibroblasts after
      irradiation. EC inhibited radiation-induced ROS generation, mitochondrial
      dysfunction and cell death. EC significantly reduced the expression of p-JNK, p
      38, and cleaved caspase-3 compared with their significant increase after
      radiation treatment. EC attenuated the radiation-induced embryotoxicity in a
      zebrafish model. These results suggest that EC represents an effective means of
      reducing cellular damage and facilitating wound healing after radiation exposure.

PMID- 23955053
TI  - Boron neutron capture therapy outcomes for advanced or recurrent head and neck
      cancer.
AB  - We retrospectively review outcomes of applying boron neutron capture therapy
      (BNCT) to unresectable advanced or recurrent head and neck cancers. Patients who
      were treated with BNCT for either local recurrent or newly diagnosed unresectable
      head or neck cancers between December 2001 and September 2007 were included.
      Clinicopathological characteristics and clinical outcomes were retrieved from
      hospital records. Either a combination of borocaptate sodium and
      boronophenylalanine (BPA) or BPA alone were used as boron compounds. In all the
      treatment cases, the dose constraint was set to deliver a dose <10-12 Gy-eq to
      the skin or oral mucosa. There was a patient cohort of 62, with a median follow
      up of 18.7 months (range, 0.7-40.8). A total of 87 BNCT procedures were
      performed. The overall response rate was 58% within 6 months after BNCT. The
      median survival time was 10.1 months from the time of BNCT. The 1- and 2-year
      overall survival (OS) rates were 43.1% and 24.2%, respectively. The major acute
      Grade 3 or 4 toxicities were hyperamylasemia (38.6%), fatigue (6.5%),
      mucositis/stomatitis (9.7%) and pain (9.7%), all of which were manageable. Three
      patients died of treatment-related toxicity. Three patients experienced carotid
      artery hemorrhage, two of whom had coexistent infection of the carotid artery.
      This study confirmed the feasibility of our dose-estimation method and that
      controlled trials are warranted. 

PMID- 23955054
TI  - High linear-energy-transfer radiation can overcome radioresistance of glioma stem
      like cells to low linear-energy-transfer radiation.
AB  - Ionizing radiation is applied as the standard treatment for glioblastoma
      multiforme (GBM). However, radiotherapy remains merely palliative, not curative,
      because of the existence of glioma stem cells (GSCs), which are regarded as
      highly radioresistant to low linear-energy-transfer (LET) photons. Here we
      analyzed whether or not high-LET particles can overcome the radioresistance of
      GSCs. Glioma stem-like cells (GSLCs) were induced from the GBM cell line A172 in
      stem cell culture medium. The phenotypes of GSLCs and wild-type cells were
      confirmed using stem cell markers. These cells were irradiated with (60)Co gamma
      rays or reactor neutron beams. Under neutron-beam irradiation, high-LET proton
      particles can be produced through elastic scattering or nitrogen capture
      reaction. Radiosensitivity was assessed by a colony-forming assay, and the DNA
      double-strand breaks (DSBs) were assessed by a histone gamma-H2AX focus detection
      assay. In stem cell culture medium, GSLCs could form neurosphere-like cells and
      express neural stem cell markers (Sox2 and Musashi) abundantly in comparison with
      their parental cells. GSLCs were significantly more radioresistant to gamma rays
      than their parental cells, but neutron beams overcame this resistance. There were
      significantly fewer gamma-H2AX foci in the A172 GSLCs 24 h after irradiation with
      gamma rays than in their parental cultured cells, while there was no apparent
      difference following neutron-beam irradiation. High-LET radiation can overcome
      the radioresistance of GSLCs by producing unrepairable DNA DSBs. High-LET
      radiation therapy might have the potential to overcome GBM's resistance to X-rays
      in a clinical setting. 

PMID- 23955055
TI  - Predictors of adherence to behavioral counseling and medication among female
      prisoners enrolled in a smoking cessation trial.
AB  - Smoking is highly prevalent among prison populations. Adherence to counseling and
      nicotine replacement therapy predicts successful cessation. The authors examined
      predictors of >= 80% adherence to counseling and nicotine patch in a cessation
      trial targeting female prisoners. Of the 202 participants included in these
      analyses, 66.8% were adherent to the patch, 51.2% were adherent to counseling,
      16.3% were nonadherent to both, and 45.0% were adherent to both. Older age of
      smoking initiation (p = .01), higher baseline smoking (p = .03), and prior
      substance abuse treatment (p = .04) predicted counseling adherence. Predictors of
      patch adherence included greater prior smoking level (p = .07) and more quit
      attempts (p = .09). The predictors of adherence to both was more prior quit
      attempts (p = .04). Understanding adherence-related factors may increase
      effectiveness of cessation interventions. 

PMID- 23955056
TI  - The evaluation of mental health screening practices within a population of
      incarcerated women.
AB  - Screening for mental illness within prison populations is vital to the safety and
      well-being of prisoners and to the operation of an institution. Although prisons
      are currently mandated to screen for mental illness, there are no standardized
      methods for doing so. Some prisons use specialized mental health screening
      measures while others simply ask a few face-valid mental health-related
      questions. The current study examined the validity of the latter method within a
      population of female prisoners. Quickview questions, selected to serve as mental
      health screening questions, were compared with the Minnesota Multiphasic
      Personality Inventory-2, a widely used forensic assessment measure. Results did
      not provide support for using the Quickview questions as a method for prison
      mental health screening. Implications and future directions are discussed. 

PMID- 23955058
TI  - Effects of temporal asynchrony and stimulus magnitude on competitive audio-visual
      binding.
AB  - When making decisions as to whether or not to bind auditory and visual
      information, temporal and stimulus factors both contribute to the presumption of
      multimodal unity. In order to study the interaction between these factors, we
      conducted an experiment in which auditory and visual stimuli were placed in
      competitive binding scenarios, whereby an auditory stimulus was assigned to
      either a primary or a secondary anchor in a visual context (VAV) or a visual
      stimulus was assigned to either a primary or secondary anchor in an auditory
      context (AVA). Temporal factors were manipulated by varying the onset of the to
      be-bound stimulus in relation to the two anchors. Stimulus factors were
      manipulated by varying the magnitudes of the visual (size) and auditory
      (intensity) signals. The results supported the dominance of temporal factors in
      auditory contexts, in that effects of time were stronger in AVA than in VAV
      contexts, and stimulus factors in visual contexts, in that effects of magnitude
      were stronger in VAV than in AVA contexts. These findings indicate the precedence
      for temporal factors, with particular reliance on stimulus factors when the to-be
      assigned stimulus was temporally ambiguous. Stimulus factors seem to be driven by
      high-magnitude presentation rather than cross-modal congruency. The interactions
      between temporal and stimulus factors, modality weighting, discriminability, and
      object representation highlight some of the factors that contribute to audio
      visual binding. 

PMID- 23955059
TI  - Experience with a talker can transfer across modalities to facilitate lipreading.
AB  - Rosenblum, Miller, and Sanchez (Psychological Science, 18, 392-396, 2007) found
      that subjects first trained to lip-read a particular talker were then better able
      to perceive the auditory speech of that same talker, as compared with that of a
      novel talker. This suggests that the talker experience a perceiver gains in one
      sensory modality can be transferred to another modality to make that speech
      easier to perceive. An experiment was conducted to examine whether this cross
      sensory transfer of talker experience could occur (1) from auditory to lip-read
      speech, (2) with subjects not screened for adequate lipreading skill, (3) when
      both a familiar and an unfamiliar talker are presented during lipreading, and (4)
      for both old (presentation set) and new words. Subjects were first asked to
      identify a set of words from a talker. They were then asked to perform a
      lipreading task from two faces, one of which was of the same talker they heard in
      the first phase of the experiment. Results revealed that subjects who lip-read
      from the same talker they had heard performed better than those who lip-read a
      different talker, regardless of whether the words were old or new. These results
      add further evidence that learning of amodal talker information can facilitate
      speech perception across modalities and also suggest that this information is not
      restricted to previously heard words. 

PMID- 23955060
TI  - The preferential binding of a sensory organ specific odorant binding protein of
      the alfalfa plant bug Adelphocoris lineolatus AlinOBP10 to biologically active
      host plant volatiles.
AB  - Semiochemicals such as sex pheromones and plant volatiles are crucial components
      of insect mating systems and host plant localization. In the olfactory signal
      transduction pathway, odorant-binding proteins (OBPs) are important elements that
      function in the first step of the pathway by carrying hydrophobic semiochemicals
      across the sensillum lymph to the olfactory receptors (ORs). In this study, we
      examined the binding affinities of semiochemicals to AlinOBP10, a putative OBP
      from the alfalfa plant bug, Adelphocoris lineolatus, that we demonstrate is
      expressed mainly in sensory organs. We then characterized the biological
      activities of the high affinity semiochemicals by measuring their
      electrophysiological activities in antennae and behavioral responses in the plant
      bug. AlinOBP10 displayed weak binding affinities to two major putative pheromone
      components, hexyl butyrate and (E)-2-hexenyl butyrate. In contrast, AlinOBP10
      exhibited higher binding affinities to six host plant volatiles, namely myrcene,
      beta-pinene, beta-ionone, 3-hexanone, (E)-2-hexenal, and 1-hexanol. The
      biological activities of these six putative ligands were further studied in
      electroantennogram recordings and Y-tube olfactometer trials. The three
      compounds, (E)-2-hexenal, 1-hexanol, and 3-hexanone elicited strong
      electrophysiological responses, but elicited distinct behaviors. While 3-hexanone
      was attractive to female adults, (E)-2-hexenal and 1-hexanol were significant
      repellents. Although a weak electrophysiological response was elicited with beta
      pinene, it was a strong repellent. These results demonstrate that AlinOBP10 can
      interact with attractants, as well as repellents, with some specificity toward
      plant volatiles over sex pheromones. 

PMID- 23955061
TI  - The lodgepole * jack pine hybrid zone in Alberta, Canada: a stepping stone for
      the mountain pine beetle on its journey East across the boreal forest?
AB  - Historical data show that outbreaks of the tree killing mountain pine beetle are
      often preceded by periods of drought. Global climate change impacts drought
      frequency and severity and is implicated in the range expansion of the mountain
      pine beetle into formerly unsuitable habitats. Its expanded range has recently
      reached the lodgepole * jack pine hybrid zone in central Alberta, Canada, which
      could act as a transition from its historical lodgepole pine host to a jack pine
      host present in the boreal forest. This field study tested the effects of water
      limitation on chemical defenses of mature trees against mountain pine beetle
      associated microorganisms and on beetle brood success in lodgepole * jack pine
      hybrid trees. Tree chemical defenses as measured by monoterpene emission from
      tree boles and monoterpene concentration in needles were greater in trees that
      experienced water deficit compared to well-watered trees. Myrcene was identified
      as specific defensive compound, since it significantly increased upon inoculation
      with dead mountain pine beetles. Beetles reared in bolts from trees that
      experienced water deficit emerged with a higher fat content, demonstrating for
      the first time experimentally that drought conditions benefit mountain pine
      beetles. Further, our study demonstrated that volatile chemical emission from
      tree boles and phloem chemistry place the hybrid tree chemotype in-between
      lodgepole pine and jack pine, which might facilitate the host shift from
      lodgepole pine to jack pine. 

PMID- 23955057
TI  - Protein carriers of conjugate vaccines: characteristics, development, and
      clinical trials.
AB  - The immunogenicity of polysaccharides as human vaccines was enhanced by coupling
      to protein carriers. Conjugation transformed the T cell-independent
      polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that
      were much more immunogenic and launched a renaissance in vaccinology. This review
      discusses the conjugate vaccines for prevention of infections caused by
      Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria
      meningitidis. Specifically, the characteristics of the proteins used in the
      construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid,
      Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein
      D are discussed. The studies that established differences among and key features
      of conjugate vaccines including immunologic memory induction, reduction of
      nasopharyngeal colonization and herd immunity, and antibody avidity and avidity
      maturation are presented. Studies of dose, schedule, response to boosters, of
      single protein carriers with single and multiple polysaccharides, of multiple
      protein carriers with multiple polysaccharides and conjugate vaccines
      administered concurrently with other vaccines are discussed along with
      undesirable consequences of conjugate vaccines. The clear benefits of conjugate
      vaccines in improving the protective responses of the immature immune systems of
      young infants and the senescent immune systems of the elderly have been made
      clear and opened the way to development of additional vaccines using this
      technology for future vaccine products. 

PMID- 23955062
TI  - Nucleophilic addition of carborane anion to Ir, Rh-coordinated Cp* ring: C-C bond
      formation accompanied by reduction of metal center.
AB  - Reaction of carboranyl anion or its thiolate derivative with a fully-substituted
      Cp*-based group 9 (Ir, Rh) metal complex affords respectively a C-C bond
      formation complex and a salt metathesis product. This example represents the
      first nucleophilic addition attempt in the area of M-Cp* chemistry. 

PMID- 23955063
TI  - Chondroitin and glucosamine in the management of osteoarthritis: an update.
AB  - The objective of osteoarthritis (OA) treatment is not only control of symptoms
      (i.e. reducing pain and improving function) but also to preserve joint structure
      and maintain quality of life. OA management remains challenging. Glucosamine and
      chondroitin are two compounds available for treatment of OA patients. Taken alone
      or in combination, they have a good safety profile and a variety of effects. In
      vitro and in-vivo experiments have revealed that both compounds induced key
      intermediates in the OA pathophysiological process. Clinical trials, although
      providing conflicting and questionable results, report symptomatic and structure
      modifying effects for both pharmaceutical-grade compounds. This review will
      discuss all these subjects and emphasize the importance of the quality of tested
      compounds for achieving high quality clinical trials. 

PMID- 23955064
TI  - Biomarkers in ANCA-associated vasculitis.
AB  - Despite recent advances in the treatment of antineutrophil cytoplasmic
      autoantibody (ANCA)-associated vasculitis (AAV), relapse remains common and
      patients often experience a variable clinical course after initial treatment. New
      biomarkers are needed to aid the management of these complex diseases.
      Discoveries regarding the pathogenesis of AAV, from the importance both of
      activated B and T cells and the alternative complement pathway to genomic data,
      may lay the groundwork for identification of novel biomarkers. 

PMID- 23955065
TI  - Changing incidence of orthopedic surgery in rheumatic disease: contributing
      factors.
AB  - Rheumatic diseases are multisystem conditions that predominantly affect the
      musculoskeletal system, leading to soft tissue and articular damage.
      Historically, medical therapy was able to slow, but not prevent, erosion and
      joint destruction, resulting in the frequent need for orthopedic procedures to
      maintain function and minimize pain. However, the widespread use of disease
      modifying anti-rheumatic drugs (DMARDs) and biologic therapy over the last twenty
      years has resulted in a dramatic decrease in the incidence of musculoskeletal
      damage and impairment among these patients. This review will discuss changing
      patterns of orthopedic surgery among patients with rheumatic diseases, focusing
      on rheumatoid arthritis and systemic lupus erythematosus. 

PMID- 23955066
TI  - ACPA and bone loss in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by
      bone loss. Degree of inflammation and autoantibody positivity have both been
      identified as important initiators of skeletal damage in RA. Whereas it is well
      appreciated that inflammation initiates bone loss via the action of cytokines,
      the effect of autoantibodies in initiating bone destruction has long been
      underestimated. It has, nonetheless, been known for years that antibodies against
      citrullinated proteins (ACPA) and rheumatoid factor are associated with a more
      destructive disease course. It was recently shown that ACPA bind osteoclast
      precursor cells and directly promote their differentiation into bone-resorbing
      osteoclasts. Other results have shown that in ACPA-positive individuals bone loss
      starts even before the onset of clinical disease; this is indicative of the
      independent effect of these antibodies in initiating skeletal damage. The
      observation that the mere presence of ACPA is associated with pathological
      changes suggests that these antibodies have functional properties and initiate
      the onset of disease long before patients consult the rheumatologist because of
      symptomatic joint disease. These findings also indicate that "RA" is a syndrome
      rather than a single disease, suggesting that autoantibody-positive patients are
      both genetically and clinically distinct phenotypes. 

PMID- 23955067
TI  - Cell-signaling therapy in rheumatoid arthritis.
AB  - New treatments for rheumatoid arthritis (RA) continue to emerge to meet
      unsatisfied needs of a significant number of patients. The development of new,
      oral biologic therapy is a significant step forward, although these drugs will
      require further evaluation in clinical settings before their true potential is
      appreciated. This new, oral biologic therapy has mostly focused on inhibition of
      intracellular signaling. These mechanisms and the available studies regarding the
      efficacy and safety of specific drugs which interfere with these mechanisms are
      the subject of this article. 

PMID- 23955068
TI  - Molecular characterization of human parainfluenza virus type 1 in infants
      attending Mbagathi District Hospital, Nairobi, Kenya: a retrospective study.
AB  - Human parainfluenza virus type 1 (HPIV-1), a paramyxovirus, is a leading cause of
      pediatric respiratory hospitalizations globally. Currently, there is no
      clinically successful vaccine against HPIV-1. Hence, there is a need to
      characterize circulating strains of this virus to establish the feasibility of
      developing a vaccine against the virus. The variable HPIV-1 hemagglutin
      neuraminidase (HN) protein is found in the envelope of HPIV-1, where it initiates
      the infection process by binding to cellular receptors. HN is also the major
      antigen against which the human immune response is directed against. The present
      study focused on identifying mutations in the HN gene that would be useful in
      understanding the evolution of HPIV-1. 21 HPIV-1 isolates were obtained after
      screening nasopharyngeal samples from patients with influenza-like illness. The
      samples were collected from Mbagathi District Hospital Nairobi from the period
      July 2007 to December 2010. RT-PCR was carried out on the isolates using HN
      specific primers to amplify a 360 nt in the most polymorphic region and the
      amplicons sequenced. Genomic data were analysed using a suite of bioinformatic
      software. Forty eight polymorphic sites with a total of 55 mutations were
      identified at the nucleotide level and 47 mutations at 23 positions at the amino
      acid level. There was more radical nonsynonymous amino acid changes (seven
      positions) observed than conservative nonsynonymous changes (one position) on the
      HN gene fragment. No positively selected sites were found in the HN protein. The
      result from the analysis of 21 HPIV-1 Mbagathi isolates demonstrated that the HN
      gene which is the major antigenic target was under purifying (negative) selection
      displaying evolutionary stasis.

PMID- 23955070
TI  - Adsorption-induced stability reversal of photochromic diarylethene on metal
      surfaces.
AB  - A scanning tunneling microscopy study of a photochromic diarylethene adsorbed on
      Au and Cu reveals the reversal of thermodynamic stability between its two isomers
      compared to the gas phase, in solution, and its single crystal, which could
      result from the molecule-substrate interaction such as charge transfer and
      hybridization. 

PMID- 23955069
TI  - Assembly and organization of poly(3-hexylthiophene) brushes and their potential
      use as novel anode buffer layers for organic photovoltaics.
AB  - Buffer layers that control electrochemical reactions and physical interactions at
      electrode/film interfaces are key components of an organic photovoltaic cell.
      Here the structure and properties of layers of semi-rigid poly(3-hexylthiophene)
      (P3HT) chains tethered at a surface are investigated, and these functional
      systems are applied in an organic photovoltaic device. Areal density of P3HT
      chains is readily tuned through the choice of polymer molecular weight and
      annealing conditions, and insights from optical absorption spectroscopy and
      semiempirical quantum calculation methods suggest that tethering causes
      intrachain defects that affect co-facial pi-stacking of brush chains. Because of
      their ability to modify oxide surfaces, P3HT brushes are utilized as an anode
      buffer layer in a P3HT-PCBM (phenyl-C61-butyric acid methyl ester) bulk
      heterojunction device. Current-voltage characterization shows a significant
      enhancement in short circuit current, suggesting the potential of these novel
      nanostructured buffer layers to replace the PEDOT:PSS buffer layer typically
      applied in traditional P3HT-PCBM solar cells.

PMID- 23955072
TI  - Generalized pustular eruptions: time to adapt the disease taxonomy to the genetic
      architecture?

PMID- 23955071
TI  - RAF inhibition overcomes resistance to TRAIL-induced apoptosis in melanoma cells.
AB  - Mutated BRAF represents a critical oncogene in melanoma, and selective inhibitors
      have been approved for melanoma therapy. However, the molecular consequences of
      RAF inhibition in melanoma cells remained largely elusive. Here, we investigated
      the effects of the pan-RAF inhibitor L-779,450, which inhibited cell
      proliferation both in BRAF-mutated and wild-type melanoma cell lines. It
      furthermore enhanced apoptosis in combination with the death ligand tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) and overcame TRAIL
      resistance in melanoma cells. Enhanced apoptosis coincided with activation of
      mitochondrial pathways, seen by loss of mitochondrial membrane potential and
      release of cytochrome c, Smac (second mitochondria-derived activator of
      caspases), and apoptosis-inducing factor (AIF). Subsequently, caspase-9 and -3
      were activated. Apoptosis induction by L-779,450/TRAIL was prevented by Bcl-2
      overexpression and was dependent on Bax. Thus, activation of Bax by L-779,450
      alone was demonstrated by Bax conformational changes, whereas Bak was not
      activated. Furthermore, the BH3-only protein Bim was upregulated in response to L
      779,450. The significant roles of Smac, Bax, and Bim in this setting were proven
      by small interfering RNA (siRNA)-mediated knockdown experiments. L-779,450 also
      resulted in morphological changes indicating autophagy confirmed by the autophagy
      marker light chain 3-II (LC3-II). The pro-apoptotic effects of L-779,450 may
      explain the antitumor effects of RAF inhibition and may be considered when
      evaluating RAF inhibitors for melanoma therapy. 

PMID- 23955073
TI  - PI3K inhibitor GDC-0941 enhances apoptotic effects of BH-3 mimetic ABT-737 in AML
      cells in the hypoxic bone marrow microenvironment.
AB  - Both phosphatidylinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin
      signaling and antiapoptotic Bcl-2 family members are critical for survival of
      acute myeloid leukemia (AML) cells. Here, we demonstrate the antileukemic effects
      of simultaneous inhibition of PI3K by the selective class I PI3K inhibitor GDC
      0941 and of Bcl-2 family members by the BH3 mimetic ABT-737 in the context of the
      bone marrow microenvironment, where hypoxia and interactions with bone marrow
      stromal cells promote AML cell survival and chemoresistance. The combination of
      GDC-0941 and ABT-737 profoundly downregulated antiapoptotic Mcl-1 expression
      levels, activated BAX, and induced mitochondrial apoptosis in AML cells co
      cultured with bone marrow stromal cells under hypoxic conditions. Hypoxia caused
      degradation of Mcl-1 and rendered Mcl-1-overexpressing OCI-AML3 cells sensitive
      to ABT-737. Our findings suggest that pharmacologic PI3K inhibition by GDC-0941
      enhances ABT-737-induced leukemia cell death even under the protective conditions
      afforded by the bone marrow microenvironment. KEY MESSAGE: Combined blockade of
      PI3K and Bcl-2 pathways down-regulates anti-apoptotic Mcl-1 expression PI3K and
      Bcl-2 induced Mcl-1 down-regulation activates BAX PI3K and Bcl-2 blockage induces
      apoptosis in AML under hypoxic BM microenvironment.

PMID- 23955074
TI  - Bendamustine combined with rituximab for patients with relapsed or refractory
      diffuse large B cell lymphoma.
AB  - Patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) are
      treated with salvage regimens and may be considered for high-dose chemotherapy
      and autologous stem cell transplantation if disease is chemosensitive.
      Bendamustine is active in indolent B cell lymphomas and chronic lymphocytic
      leukemia but has not been extensively studied in aggressive lymphomas. This trial
      examines the combination of bendamustine and rituximab in patients with relapsed
      and refractory DLBCL. Patients received bendamustine at 90 mg/m2 (n = 2) or 120
      mg/m2 (n = 57) on days 1 and 2 and rituximab at 375 mg/m2 on day 1 every 28 days
      for up to 6 cycles. The study evaluated objective response rate (ORR), duration
      of response (DOR), progression-free survival (PFS), and treatment safety. Fifty
      nine patients were treated, and 48 were evaluable for response. Median age was
      74; 89 % had stage III or IV disease, and 63 % had high revised International
      Prognostic Index scores; the median number of prior therapies was 1. Based on
      analysis using the intent-to-treat population, the ORR was 45.8 % (complete
      response, 15.3 %; partial response, 30.5 %). The median DOR was 17.3 months, and
      the median PFS was 3.6 months. Grade 3 or 4 hematological toxicities included
      neutropenia (36 %), leukopenia (29 %), thrombocytopenia (22 %), and anemia (12
      %). The combination of bendamustine and rituximab showed modest activity in
      patients with relapsed and refractory DLBCL and has an acceptable toxicity
      profile.

PMID- 23955076
TI  - Inducible expression of hyperactive Syk in B cells activates Blimp-1-dependent
      terminal differentiation.
AB  - The non-receptor protein tyrosine kinase Syk (spleen tyrosine kinase) is an
      important mediator of signal transduction in B cells. By acting downstream of the
      B-cell antigen receptor, Syk promotes signaling pathways involved in
      proliferation, differentiation and survival of B cells. To study the oncogenic
      potential of Syk, we generated a mouse model for the inducible expression of the
      leukemia-derived TEL-Syk fusion protein exhibiting constitutive kinase activity.
      To achieve B-cell-specific expression of TEL-Syk in adult mice, we used a
      tamoxifen-inducible Cre mouse line. This study shows that inducible expression of
      TEL-Syk in B cells leads to transient proliferation and subsequent plasma cell
      differentiation. However, it does not lead to B-cell transformation. Instead, Syk
      activation induces the tumor suppressor B-lymphocyte-induced maturation protein-1
      (Blimp-1), which interferes with the expression of the antiapoptotic protein Bcl
      2. Combined induction of TEL-Syk with transgenic expression of Bcl-2 results in a
      severe phenotype and plasma cell expansion. Our results suggest that deregulated
      Syk activity by itself is not sufficient for the transformation of B cells, as
      downstream effectors, such as Blimp-1, limit the survival and expansion of the
      activated B cell. 

PMID- 23955075
TI  - Salivary cortisol and cold pain sensitivity in female twins.
AB  - BACKGROUND: There is a dearth of knowledge about the link between cortisol and
      pain sensitivity. PURPOSE: We examined the association of salivary cortisol with
      indices of cold pain sensitivity in 198 female twins and explored the role of
      familial confounding. METHODS: Three-day saliva samples were collected for
      cortisol levels and a cold pressor test was used to collect pain ratings and time
      to threshold and tolerance. Linear regression modeling with generalized
      estimating equations examined the overall and within-pair associations. RESULTS:
      Lower diurnal variation of cortisol was associated with higher pain ratings at
      threshold (p = 0.02) and tolerance (p < 0.01). The relationship of diurnal
      variation with pain ratings at threshold and tolerance was minimally influenced
      by familial factors (i.e., genetics and common environment). CONCLUSIONS:
      Understanding the genetic and non-genetic mechanisms underlying the link between
      HPA axis dysregulation and pain sensitivity may help to prevent chronic pain
      development and maintenance.

PMID- 23955077
TI  - Stefin B deficiency reduces tumor growth via sensitization of tumor cells to
      oxidative stress in a breast cancer model.
AB  - Lysosomal cysteine cathepsins contribute to proteolytic events promoting tumor
      growth and metastasis. Their enzymatic activity, however, is tightly regulated by
      endogenous inhibitors. To investigate the role of cathepsin inhibitor stefin B
      (Stfb) in mammary cancer, Stfb null mice were crossed with transgenic polyoma
      virus middle T oncogene (PyMT) breast cancer mice. We show that ablation of Stfb
      resulted in reduced size of mammary tumors but did not affect their rate of
      metastasis. Importantly, decrease in tumor growth was correlated with an
      increased incidence of dead cell islands detected in tumors of Stfb-deficient
      mice. Ex vivo analysis of primary PyMT tumor cells revealed no significant
      effects of ablation of Stfb expression on proliferation, angiogenesis, migration
      and spontaneous cell death as compared with control cells. However, upon
      treatment with the lysosomotropic agent Leu-Leu-OMe, cancer cells lacking Stfb
      exhibited a significantly higher sensitivity to apoptosis. Moreover, Stfb-ablated
      tumor cells were significantly more prone to cell death under increased oxidative
      stress. These results indicate an in vivo role for Stfb in protecting cancer
      cells by promoting their resistance to oxidative stress and to apoptosis induced
      through the lysosomal pathway. 

PMID- 23955078
TI  - The telomere profile distinguishes two classes of genetically distinct cutaneous
      squamous cell carcinomas.
AB  - The incidence of skin cancer is increasing worldwide and cutaneous squamous cell
      carcinomas (SCCs) are associated with considerable morbidity and mortality,
      particularly in immunosuppressed individuals ('carcinomatous catastrophy'). Yet,
      molecular mechanisms are still insufficiently understood. Besides ultraviolet
      (UV)-indicative mutations, chromosomal aberrations are prominent. As telomeres
      are essential in preserving chromosome integrity, and telomere erosion as well as
      aberrant spatial telomere distribution contribute to genomic instability, we
      first established telomere length profiles across the whole tissue and identified
      normal skin (10/30) harboring discrete epidermal sites (stem cell territories) of
      evenly short telomeres. Precancerous actinic keratoses (AKs) (17) and SCCs (27)
      expressed two telomere phenotypes: (i) tissue-wide evenly short to intermediate
      and (ii) longer and tissue-wide heterogeneous telomere lengths, suggesting two
      modes of initiation, with one likely to originate in the epidermal stem cells.
      Although tumor histotype, location, patient gender or age failed to distinguish
      the two SCC telomere phenotypes, as did telomerase activity, we found a trend for
      a higher degree of aberrant p53 and cyclin D1 expression with long/heterogeneous
      telomeres. In addition, we established an association for the short/homogeneous
      telomeres with a simpler and the heterogeneous telomeres with a more complex
      karyotype correlating also with distinct chromosomal changes. SCCs (13) from
      renal transplant recipients displayed the same telomere dichotomy, suggesting
      that both telomere subtypes contribute to 'carcinomatous catastrophy' under
      immunosuppression by selecting for a common set (3, 9p and 17q) and subtype
      specific aberrations (e.g., 6p gain, 13q loss). As a second mechanism of telomere
      dependent genomic instability, we investigated changes in telomere distribution
      with its most severe form of telomeric aggregates (TAs). We identified a telomere
      length-independent but progression-dependent increase in cells with small
      telomere associations in AKs (17/17) and additional TAs in SCCs (24/32), basal
      cell carcinomas (30/31) and malignant melanomas (15/15), and provide evidence for
      a reactive oxygen species-dependent mechanism in this UV-induced telomere
      organization-dependent genomic instability. 

PMID- 23955079
TI  - Opportunities and hurdles in the treatment of BRCA1-related breast cancer.
AB  - BRCA1 functions as a classical tumor suppressor in breast and ovarian cancer.
      While the role of BRCA1 in homology-directed repair of DNA double-strand breaks
      contributes to its tumor suppressive activity, it also renders BRCA1-deficient
      cells highly sensitive to DNA-damaging agents. Although BRCA1 deficiency is
      therefore considered to be an attractive therapeutic target, re-activation of
      BRCA1 by secondary mutations has been shown to cause therapy resistance. In this
      review, we will assess the role of BRCA1 in both hereditary and sporadic breast
      cancer and discuss how different functionalities of the BRCA1 protein can
      contribute to its tumor suppressor function. In addition, we will discuss how
      this knowledge on BRCA1 function can help to overcome the hurdles encountered in
      the clinic and improve current treatment strategies for patients with BRCA1
      related breast cancer.

PMID- 23955080
TI  - A peptide that inhibits function of Myristoylated Alanine-Rich C Kinase Substrate
      (MARCKS) reduces lung cancer metastasis.
AB  - Myristoylated Alanine-Rich C Kinase Substrate (MARCKS), a substrate of protein
      kinase C, is a key regulatory molecule controlling mucus granule secretion by
      airway epithelial cells as well as directed migration of leukocytes, stem cells
      and fibroblasts. Phosphorylation of MARKCS may be involved in these responses.
      However, the functionality of MARCKS and its related phosphorylation in lung
      cancer malignancy have not been characterized. This study demonstrated elevated
      levels of MARCKS and phospho-MARCKS in highly invasive lung cancer cell lines and
      lung cancer specimens from non-small-cell lung cancer patients. siRNA knockdown
      of MARCKS expression in these highly invasive lung cancer cell lines reduced cell
      migration and suppressed PI3K (phosphatidylinositol 3'-kinase)/Akt
      phosphorylation and Slug level. Interestingly, treatment with a peptide identical
      to the MARCKS N-terminus sequence (the MANS peptide) impaired cell migration in
      vitro and also the metastatic potential of invasive lung cancer cells in vivo.
      Mechanistically, MANS peptide treatment resulted in a coordination of increase of
      E-cadherin expression, suppression of MARCKS phosphorylation and AKT/Slug
      signalling pathway but not the expression of total MARCKS. These results indicate
      a crucial role for MARCKS, specifically its phosphorylated form, in potentiating
      lung cancer cell migration/metastasis and suggest a potential use of MARCKS
      related peptides in the treatment of lung cancer metastasis. 

PMID- 23955081
TI  - Bmi1 is required for tumorigenesis in a mouse model of intestinal cancer.
AB  - The epigenetic regulator BMI1 is upregulated progressively in a wide variety of
      human tumors including colorectal cancer. In this study, we assessed the
      requirement for Bmi1 in intestinal tumorigenesis using an autochthonous mouse
      model in which Apc was conditionally ablated in the intestinal epithelium.
      Germline mutation of Bmi1 significantly reduced both the number and size of small
      intestinal adenomas arising in this model, and it acted in a dose-dependent
      manner. Moreover, in contrast to wild-type controls, Bmi1(-/-) mice showed no
      increase in median tumor size, and a dramatic decrease in tumor number, between 3
      and 4 months of age. Thus, Bmi1 is required for both progression and maintenance
      of small intestinal adenomas. Importantly, Bmi1 deficiency did not disrupt
      oncogenic events arising from Apc inactivation. Instead, the Arf tumor
      suppressor, a known target of Bmi1 epigenetic silencing, was upregulated in Bmi1
      mutant tumors. This was accompanied by significant upregulation of p53, which was
      confirmed by sequencing to be wild-type, and also elevated apoptosis within the
      smallest Bmi1(-/-) adenomas. By crossing Arf into this cancer model, we showed
      that Arf is required for the induction of both p53 and apoptosis, and it is a key
      determinant of the ability of Bmi1 deficiency to suppress intestinal
      tumorigenesis. Finally, a conditional Bmi1 mutant strain was generated and used
      to determine the consequences of deleting Bmi1 specifically within the intestinal
      epithelium. Strikingly, intestinal-specific Bmi1 deletion suppressed small
      intestinal adenomas in a manner that was indistinguishable from germline Bmi1
      deletion. Thus, we conclude that Bmi1 deficiency impairs the progression and
      maintenance of small intestinal tumors in a cell autonomous and highly Arf
      dependent manner. 

PMID- 23955082
TI  - Inflammatory lipid sphingosine-1-phosphate upregulates C-reactive protein via
      C/EBPbeta and potentiates breast cancer progression.
AB  - A crucial role of the inflammatory lipid sphingosine-1-phosphate (S1P) in breast
      cancer aggressiveness has been reported. Recent clinical studies have suggested
      that C-reactive protein (CRP) has a role in breast cancer development. However,
      limited information is available on the molecular basis for the expression of CRP
      and its functional significance in breast cell invasion. The present study aimed
      to elucidate the molecular link between S1P and CRP during the invasive process
      of breast epithelial cells. This is the first report showing that transcription
      of CRP was markedly activated by S1P in breast cells. Our data suggest that not
      only S1P treatment but also the endogenously produced S1P may upregulate CRP in
      breast carcinoma cells. Transcription factors CCAAT/enhancer-binding protein beta
      and c-fos were required for S1P-induced CRP expression. Coupling of S1P3 to
      heterotrimeric Galphaq triggered the expression of CRP, utilizing signaling
      pathways involving reactive oxygen species (ROS), Ca(2+) and extracellular signal
      related kinases (ERKs). S1P-induced CRP expression was crucial for the
      transcriptional activation of matrix metalloproteinase-9 through ERKs, ROS and c
      fos, leading to breast cell invasion. Using a xenograft mice tumor model, we
      demonstrated that S1P induced CRP expression both in vitro and in vivo. Taken
      together, our findings have revealed a molecular basis for S1P-induced
      transcriptional activation of CRP and its functional significance in the
      acquisition of the invasive phenotype of human breast epithelial cells under
      inflammatory conditions. Our findings may provide useful information on the
      identification of useful therapeutic targets for inflammatory breast cancer. 

PMID- 23955083
TI  - p53 deficiency enhances mitotic arrest and slippage induced by pharmacological
      inhibition of Aurora kinases.
AB  - A number of small-molecule inhibitors of Aurora kinases have been developed and
      are undergoing clinical trials for anti-cancer therapies. Different Aurora
      kinases, however, behave as very different targets: while inhibition of Aurora A
      (AURKA) induces a delay in mitotic exit, inhibition of Aurora B (AURKB) triggers
      mitotic slippage. Furthermore, while it is evident that p53 is regulated by
      Aurora kinase-dependent phosphorylation, how p53 may in turn regulate Aurora
      kinases remains mysterious. To address these issues, isogenic p53-containing and 
      negative cells were exposed to classic inhibitors that target both AURKA and
      AURKB (Alisertib and ZM447439), as well as to new generation of inhibitors that
      target AURKA (MK-5108), AURKB (Barasertib) individually. The fate of individual
      cells was then tracked with time-lapse microscopy. Remarkably, loss of p53,
      either by gene disruption or small interfering RNA-mediated depletion, sensitized
      cells to inhibition of both AURKA and AURKB, promoting mitotic arrest and
      slippage respectively. As the p53-dependent post-mitotic checkpoint is also
      important for preventing genome reduplication after mitotic slippage, these
      studies indicate that the loss of p53 in cancer cells represents a major
      opportunity for anti-cancer drugs targeting the Aurora kinases. 

PMID- 23955084
TI  - The role of miR-150 in normal and malignant hematopoiesis.
AB  - MicroRNAs are a class of small non-coding RNAs that have been implicated to
      mediate gene regulation in virtually all important biological processes. Recently
      there is accumulating evidence showing that miR-150 has essential regulatory
      roles in both normal and malignant hematopoiesis and holds great potential as a
      therapeutic target in treating various types of hematopoietic malignancies. The
      purpose of this review is to summarize our current knowledge about the expression
      patterns, biological functions and regulatory mechanisms of miR-150 in normal and
      malignant hematopoiesis, and to highlight the important questions to be answered
      in this burgeoning field.

PMID- 23955086
TI  - The error-prone DNA polymerase iota provides quantitative resistance to lung
      tumorigenesis and mutagenesis in mice.
AB  - Opposite undamaged nucleotide T, DNA polymerase iota (Poliota) preferentially
      incorporates G rather than A, violating the Watson-Crick rule. Although the
      actual biological role of Poliota remains enigmatic, we have identified its
      coding gene as a candidate for pulmonary adenoma resistance 2 (Par2), a mouse
      quantitative trait locus modulating chemically induced lung tumor susceptibility.
      Notably, the most tumor-sensitive Par2 allele possessed by the 129X1/SvJ mouse is
      associated with a loss-of-function mutation in Poliota. To determine whether the
      nonfunctional Poliota is responsible for the 129X1/SvJ-specific Par2 phenotype,
      we knocked out Poliota in a C57BL/6J mouse carrying a less tumor-sensitive Par2
      allele. Disruption of the C57BL/6J Poliota conferred 129X1/SvJ-like sensitivity
      on the C57BL/6J Par2 locus and increased the in vivo mutation frequency in the
      lung, providing definitive proof that Poliota causes the Par2 effect and inhibits
      tumorigenesis and mutagenesis, despite its extreme replication infidelity. 

PMID- 23955085
TI  - MiR-155-mediated loss of C/EBPbeta shifts the TGF-beta response from growth
      inhibition to epithelial-mesenchymal transition, invasion and metastasis in
      breast cancer.
AB  - During breast cancer progression, transforming growth factor-beta (TGF-beta)
      switches from acting as a growth inhibitor to become a major promoter of
      epithelial-mesenchymal transition (EMT), invasion and metastasis. However, the
      mechanisms involved in this switch are not clear. We found that loss of CCAAT
      enhancer binding protein beta (C/EBPbeta), a differentiation factor for the
      mammary epithelium, was associated with signs of EMT in triple-negative human
      breast cancer, and in invasive areas of mammary tumors in MMTV-PyMT mice. Using
      an established model of TGF-beta-induced EMT in mouse mammary gland epithelial
      cells, we discovered that C/EBPbeta was repressed during EMT by miR-155, an
      oncomiR in breast cancer. Depletion of C/EBPbeta potentiated the TGF-beta
      response towards EMT, and contributed to evasion of the growth inhibitory
      response to TGF-beta. Furthermore, loss of C/EBPbeta enhanced invasion and
      metastatic dissemination of the mouse mammary tumor cells to the lungs after
      subcutaneous injection into mice. The mechanism by which loss of C/EBPbeta
      promoted the TGF-beta response towards EMT, invasion and metastasis, was traced
      to a previously uncharacterized role of C/EBPbeta as a transcriptional activator
      of genes encoding the epithelial junction proteins E-cadherin and coxsackie virus
      and adenovirus receptor. The results identify miR-155-mediated loss of C/EBPbeta
      as a mechanism, which promotes breast cancer progression by shifting the TGF-beta
      response from growth inhibition to EMT, invasion and metastasis. 

PMID- 23955087
TI  - Relative contribution of different transmembrane segments to the CFTR chloride
      channel pore.
AB  - The membrane-spanning part of the cystic fibrosis transmembrane conductance
      regulator (CFTR) Cl(-) channel comprises 12 transmembrane (TM) alpha-helices,
      arranged in 2 symmetrical groups of 6. However, those TMs that line the channel
      pore are not completely defined. We used patch clamp recording to compare the
      accessibility of cysteine-reactive reagents to cysteines introduced into
      different TMs. Several residues in TM11 were accessible to extracellular and/or
      intracellular cysteine reactive reagents; however, no reactive cysteines were
      identified in TMs 5 or 11. Two accessible residues in TM11 (T1115C and S1118C)
      were found to be more readily modified from the extracellular solution in closed
      channels, but more readily modified from the intracellular solution in open
      channels, as previously reported for T338C in TM6. However, the effects of
      mutagenesis at S1118 (TM11) on a range of pore functional properties were
      relatively minor compared to the large effects of mutagenesis at T338 (TM6). Our
      results suggest that the CFTR pore is lined by TM11 but not by TM5 or TM7.
      Comparison with previous works therefore suggests that the pore is lined by TMs
      1, 6, 11, and 12, suggesting that the structure of the open channel pore is
      asymmetric in terms of the contributions of different TMs. Although TMs 6 and 11
      appear to undergo similar conformational changes during channel opening and
      closing, the influence of these two TMs on the functional properties of the
      narrowest region of the pore is clearly unequal. 

PMID- 23955088
TI  - Benzo-[a]-pyrene induces FAK activation and cell migration in MDA-MB-231 breast
      cancer cells.
AB  - Benzo-[a]-pyrene (B[a]P) is a family member of polycyclic aromatic hydrocarbons
      and a widespread environmental pollutant. It is a mammary carcinogen in rodents
      and contributes to the development of human breast cancer. However, the signal
      transduction pathways induced by B[a]P and its role in breast cancer progression
      have not been studied in detail. Here, we demonstrate that B[a]P induces cell
      migration through a lipoxygenase- and Src-dependent pathway, as well as the
      activation of focal adhesion kinase, Src, and the extracellular signal-regulated
      kinase 2 in MDA-MB-231 breast cancer cells. However, B[a]P is not able to promote
      migration in the mammary nontumorigenic epithelial cells MCF12A. Moreover, B[a]P
      promotes an increase of alphavbeta3 integrin-cell surface levels and an increase
      of metalloproteinase (MMP)-2 and MMP-9 secretions. In summary, our findings
      demonstrate that B[a]P induces the activation of signal transduction pathways and
      biological processes involved in the invasion/metastasis process in MDA-MB-231
      breast cancer cells. 

PMID- 23955089
TI  - Methotrexate enhances 3T3-L1 adipocytes hypertrophy.
AB  - Methotrexate (MTX) is broadly used in the treatment of chronic inflammatory
      diseases such as rheumatoid arthritis (RA). The prevalence of metabolic syndrome
      (MeS) in patients with this condition is relatively high. Given the importance of
      adipose tissue in the development of obesity metabolic complications, this study
      aimed to investigate the effect of methotrexate on preadipocyte proliferation,
      adipogenesis, and glucose uptake by adipocytes. 3T3-L1 preadipocytes
      proliferation was evaluated by sulforhodamine B staining and (3)H-thymidine
      incorporation, after 24 or 48 h of treatment with MTX (0.1 and 10 MUM).
      Preadipocytes were induced to differentiate with an appropriate adipogenic
      cocktail in the presence or absence of MTX. Adipogenesis was determined by
      measuring lipid accumulation after staining with oil red O. (3)H-Deoxyglucose
      ((3)H-DG) uptake was determined by liquid scintillation counting. MTX treatment
      reduced culture protein content in a concentration-dependent manner and (3)H
      thymidine incorporation (P < 0.05). MTX (0.1 MUM) treatment increased lipid
      accumulation and basal (3)H-DG uptake by adipocytes (P < 0.05). In 0.1 MUM MTX
      treated adipocytes, insulin stimulation did not result in an increase of (3)H-DG
      uptake, contrarily to what was observed in control cells. These results
      demonstrate that methotrexate interferes with adipocyte proliferation and
      promotes the hypertrophic growth of adipocytes. These molecular effects may have
      implications on metabolic profile of RA patients treated with MTX. 

PMID- 23955090
TI  - Mechanism of metolachlor action due to alterations in cell cycle progression.
AB  - Metolachlor, a commonly used herbicide in the Midwestern USA, functions by
      inhibiting chlorophyll and protein synthesis in target plants. Herbicide exposure
      has led to detrimental effects in several organisms, affecting their growth and
      behavior; however, its mechanism of action in nontarget organisms is not yet
      clear. The EPA does not currently have enforceable regulations for maximal limits
      allowed in drinking water. Previous growth studies from our lab have demonstrated
      that increasing metolachlor concentrations and increasing time of exposure
      results in decreased growth of liver cells. The objective of this study was to
      elucidate a mechanism for this decrease of HepG2 cell growth after herbicide
      exposure. Results show that metolachlor at environmentally relevant levels (50
      100 ppb) that previously led to decreased cell number does not lead to cell death
      by either necrosis or apoptosis. However, it was demonstrated that the levels of
      the retinoblastoma protein including two of its hyperphosphorylated forms are
      decreased in metolachlor exposed cells possibly leading to cell cycle arrest. The
      levels of another protein involved in cell cycle progression, p53, a mediator in
      the DNA damage response of cells, was not significantly altered except at the
      highest level of metolachlor (1,000 ppb) and after a 72-h exposure. These results
      suggest that the decrease in cell number after low-level metolachlor exposure is
      most likely due to an alteration in the cell cycle and not due to cell death in
      human liver cells. 

PMID- 23955091
TI  - Improvement of the energy conversion efficiency of Chlorella pyrenoidosa biomass
      by a three-stage process comprising dark fermentation, photofermentation, and
      methanogenesis.
AB  - The effects of pre-treatment methods on saccharification and hydrogen
      fermentation of Chlorella pyrenoidosa biomass were investigated. When raw biomass
      and biomass pre-treated by steam heating, by microwave heating, and by
      ultrasonication were used as feedstock, the hydrogen yields were only 8.8-12.7
      ml/g total volatile solids (TVS) during dark fermentation. When biomass was pre
      treated by steam heating with diluted acid and by microwave heating with diluted
      acid, the dark hydrogen yields significantly increased to 75.6 ml/g TVS and 83.3
      ml/g TVS, respectively. Steam heating with diluted acid is the preferred pre
      treatment method of C. pyrenoidosa biomass to improve hydrogen yield during dark
      fermentation and photofermentation, which is followed by methanogenesis to
      increase energy conversion efficiency (ECE). A total hydrogen yield of 198.3 ml/g
      TVS and a methane yield of 186.2 ml/g TVS corresponding to an overall ECE of
      34.0% were obtained through the three-stage process (dark fermentation,
      photofermentation, and methanogenesis).

PMID- 23955092
TI  - Effect of dilute acid pretreatment on the conversion of barley straw with grains
      to fermentable sugars.
AB  - This study investigated the effects of pretreatment conditions, dilute sulfuric
      acid concentration and treatment time, on the carbohydrate solubility of a
      mixture of barley straw and grain. The conditions were expressed as combined
      severity (CS) to evaluate sugar recovery from pretreated samples. Enzymatic
      hydrolysates from the lignocellulose pretreatment residues were also included to
      the results. CS was positively correlating with glucose recovery in all
      conditions, but in higher acid concentrations CS did not predict xylose recovery.
      It appeared that the residual xylan better indicate the xylose release. An
      optimal fermentable sugar yield from the mixture of barley straw and grain was
      obtained by maintaining the CS at around 1.38, corresponding to an overall
      glucose yield of 96% and a xylose yield of 57%. 

PMID- 23955093
TI  - The trifunctional antibody catumaxomab amplifies and shapes tumor-specific
      immunity when applied to gastric cancer patients in the adjuvant setting.
AB  - BACKGROUND: Patients with gastric cancer benefit from perioperative chemotherapy,
      however, treatment is toxic and many patients will relapse. The trifunctional
      antibody catumaxomab targets EpCAM on tumor cells, CD3 on T cells, and the
      Fcgamma-receptor of antigen-presenting cells. While in Europe catumaxomab is
      approved for treating malignant ascites, it has not been investigated in the
      perioperative setting and its exact immunological mode of action is unclear.
      METHODS: In our study, gastric cancer patients received neoadjuvant platinum
      based chemotherapy, one intraoperative application of catumaxomab, and 4
      postoperative doses of intraperitoneal catumaxomab. Immunomonitoring was
      performed in 6 patients before surgery, after completion of catumaxomab
      treatment, and one month later. RESULTS: Intraperitoneal application of
      catumaxomab caused an increased expression of activation markers on the patients'
      T cells. This was accompanied by a transient decrease in numbers of CXCR3(+)
      effector T cells with a T-helper (Th)-1 phenotype in the peripheral blood. All
      patients evidenced pre-existing EpCAM-specific CD4(+) and/or CD8(+) T cells.
      While these cells transiently disappeared from the blood stream after
      intraperitoneal application of catumaxomab, we detected increased numbers of
      peripheral EpCAM-specific cells and a modified EpCAM-specific T-cell repertoire 4
      weeks after completion of treatment. Finally, catumaxomab also amplified humoral
      immunity to tumor antigens other than EpCAM. CONCLUSIONS: Our findings suggest
      that catumaxomab exerts its clinical effects by (1) activating peripheral T
      cells, (2) redistributing effector T cells from the blood into peripheral
      tissues, (3) expanding and shaping of the pre-existing EpCAM-specific T-cell
      repertoire, and (4) spreading of anti-tumor immunity to different tumor antigens.

PMID- 23955094
TI  - Prospective observational study of treatment pattern, effectiveness and safety of
      zoledronic acid therapy beyond 24 months in patients with multiple myeloma or
      bone metastases from solid tumors.
AB  - PURPOSE: To study the treatment patterns, effectiveness and safety of zoledronic
      acid (ZOL) beyond 2 years of therapy, given the paucity of data on long-term
      treatment in daily clinical practice. METHODS: Patients with multiple myeloma
      (MM) or solid tumor bone metastases (STM) and at least 24 months of regular q3-4w
      ZOL therapy were followed prospectively for an additional 18 months beyond the 24
      months required for study entry. End-points included ZOL exposure, incidence of
      skeletal related events (SRE), and safety. RESULTS: In all, 298 evaluable
      patients were enrolled. The mean continuation rate of ZOL was 90.6%. Exposure to
      ZOL decreased with time in all patients, but was lower (50.0% vs. 67.6%; p<0.001)
      and with higher discontinuation rates (incidence rate ratio [IRR]=1.95; p=0.002)
      in MM compared to the STM group. ZOL suppressed the rate of SREs similarly during
      the study as compared to before inclusion (0.12 vs. 0.13 events per person-year;
      p=0.7). At 18 months, 84.5% remained SRE-free. In STM patients, persistent ZOL
      therapy was associated with lower SRE risk (hazard ratio [HR]=0.42; p=0.01), but
      not in MM. Renal deterioration occurred in 3.7% and osteonecrosis of the jaw
      (ONJ) developed in 6.0%, with dental trauma increasing ONJ risk (HR=4.67;
      p=0.002). CONCLUSIONS: Beyond 2 years of therapy, treatment patterns of ZOL were
      heterogeneous and SRE rates were low. The safety profile of ZOL was acceptable,
      and interrupting ZOL in patients with solid tumors was associated with a higher
      risk of SREs.

PMID- 23955095
TI  - Comparison of physical and mental health status between cancer survivors and the
      general population: a Korean population-based survey (KNHANES II-IV).
AB  - PURPOSE: To compare the physical and mental health status of the general
      population with that of cancer survivors in South Korea. METHODS: We analyzed
      19,035 subjects (age >=40 years), who participated in the 2001-2009 Korea
      National Health and Nutrition Examination Survey II-IV. We compared metabolic
      syndrome components, health behaviors, and mental health outcomes between cancer
      survivors and non-cancer controls. RESULTS: Cancer survivors accounted for 1.68 %
      (n = 316) of total population. Cancer survivors did not show low occurrence of
      hypertension and diabetes compared to the control group. Both cancer survivors
      and the general population had high risks of physical inactivity (75.4 % and 75.5
      %, respectively) and inadequate sleep (52.5 % and 60.7 %, respectively). In the
      unadjusted model, depression was more common in cancer survivors (odds ratio
      [OR], 1.61; 95 % CI, 1.22-2.74), so was suicidal ideation (OR, 1.51; 95 % CI,
      0.16-1.96) than non-cancer controls. After adjustment for attributable
      socioeconomic factors, the elevated adjusted odds ratios (aORs) among cancer
      survivors were reduced by 23 % in depression and 45 % in suicidal thought. Cancer
      survivors at <5 years from diagnosis showed a high occurrence of depression (aOR,
      1.77; 95 % CI, 1.09-2.85) while the magnitude of aOR decreases after >=5 years
      from cancer diagnosis (aOR, 1.38; 95 % confidence interval, 0.97-1.98,
      respectively). CONCLUSIONS: The physical and mental health of South Korean cancer
      survivors was not optimal. Their control rates of modifiable risk factors were
      similar or even lower than those for the non-cancer groups. Depression was highly
      prevalent in cancer survivors which can be ascribed, at least in part, to
      socioeconomic environment. A better-targeted intervention to improve the health
      of this population may be needed.

PMID- 23955096
TI  - Quantitative evaluation of hyperbaric oxygen efficacy in experimental traumatic
      brain injury: an MRI study.
AB  - To use DCE-magnetic resonance imaging (MRI) and diffusion-weighted imaging to
      evaluate the hyperbaric oxygen efficacy (HBO) in experimental traumatic brain
      injury (TBI). Forty-two rabbits were randomly divided into four groups: TBI, TBI
      + HBO, sham group, sham + HBO. The TBI + HBO and sham + HBO received a total of
      10 HBO treatments within 7 days following TBI, and MRI was performed within a
      month after TBI. Functional assessments were performed pre-TBI, and at 1 and 30
      days. In focal lesion area, K(trans) in TBI + HBO group was lower than TBI group
      at both acute and subacute phase (p < 0.05). ADC was higher in TBI + HBO group
      than TBI group at acute phase (p < 0.01), but lower at subacute phase (p < 0.05).
      In perifocal area, K(trans) were lower in TBI + HBO group than TBI group at acute
      phase (p < 0.01) after TBI. ADC was lower in the TBI + HBO group than in the TBI
      group at both acute and subacute phase (p < 0.01).The VCS was higher in TBI + HBO
      group than TBI group at 30 days (p < 0.05). HBO could improve the impaired BBB
      and cytotoxic edema after TBI and promote the recovery of neurofunction.

PMID- 23955097
TI  - Nuclear localization of huntingtin during spermatogenesis.
AB  - Huntingtin is a ubiquitous cytoplasmic protein. Mutant huntingtin causes
      Huntington's disease and its intranuclear inclusion is associated with
      cytotoxicity. Nuclear localization of normal huntingtin is detected in the oocyte
      up to 2.5 days post coitum. Therefore, huntingtin is expected to reside in the
      nucleus even before fertilization. The present study determined normal huntingtin
      distribution during spermatogenesis. Testicles from an adult male Sprague-Dawley
      rat were stained with anti-huntingtin antibody and nuclear counterstaining was
      performed with 4',6-diamidino-2-phenylindole. Concerning nuclear localization,
      huntingtin was detected in the spermatids, whereas predominant cytoplasmic
      localization of it was evident in the spermatogonia. Between the primary and
      secondary spermatocytes, huntingtin appeared to be delocalized in the nuclei when
      meiosis occurred. The findings provide evidence that normal huntingtin is
      transported to the nuclear compartment during the meiotic stage of
      spermatogenesis.

PMID- 23955098
TI  - Predominant expression of exon 7 skipped SMN mRNAs in lung based on analysis of
      transcriptome sequencing datasets.
AB  - Spinal muscular atrophy (SMA) is caused by deletion of SMN1, one of the two SMN
      (Survival of Motor Neuron) genes. SMN2 is still present in SMA patients but its
      exon 7 is alternatively spliced. In this study, we took advantage of recent
      deposit of deep-sequencing datasets from a number of human tissues and examined
      the expression and splicing of SMN mRNA. We showed that SMN is slightly more
      abundantly expressed in the lungs and prostate. More interestingly, we found that
      the percentage of SMNDelta7 in lung and adipose tissue is significantly higher
      than in other tissues such as the testes, where almost no SMNDelta7 is expressed.
      Since SMN1 produces more than 95 % of full-length SMN RNA, it is likely that SMN2
      has a higher skipping rate of exon 7 in adipose and lung tissue, leading to a
      higher ratio of SMNDelta7/SMN in these tissues. Given that many SMA patients die
      from respiratory failure, we speculate that higher skipping of exon 7 in the
      lungs may play a role in the progression of SMA.

PMID- 23955099
TI  - A titratable two-step transcriptional amplification strategy for targeted gene
      therapy based on ligand-induced intramolecular folding of a mutant human estrogen
      receptor.
AB  - PURPOSE: The efficacy and safety of cardiac gene therapy depend critically on the
      level and the distribution of therapeutic gene expression following vector
      administration. We aimed to develop a titratable two-step transcriptional
      amplification (tTSTA) vector strategy, which allows modulation of
      transcriptionally targeted gene expression in the myocardium. PROCEDURES: We
      constructed a tTSTA plasmid vector (pcTnT-tTSTA-fluc), which uses the cardiac
      troponin T (cTnT) promoter to drive the expression of the recombinant
      transcriptional activator GAL4-mER(LBD)-VP2, whose ability to transactivate the
      downstream firefly luciferase reporter gene (fluc) depends on the binding of its
      mutant estrogen receptor (ER(G521T)) ligand binding domain (LBD) to an ER ligand
      such as raloxifene. Mice underwent either intramyocardial or hydrodynamic tail
      vein (HTV) injection of pcTnT-tTSTA-fluc, followed by differential modulation of
      fluc expression with varying doses of intraperitoneal raloxifene prior to
      bioluminescence imaging to assess the kinetics of myocardial or hepatic fluc
      expression. RESULTS: Intramyocardial injection of pcTnT-tTSTA-fluc followed by
      titration with intraperitoneal raloxifene led to up to tenfold induction of
      myocardial fluc expression. HTV injection of pcTnT-tTSTA-fluc led to negligible
      long-term hepatic fluc expression, regardless of the raloxifene dose given.
      CONCLUSIONS: The tTSTA vector strategy can effectively modulate transgene
      expression in a tissue-specific manner. Further refinement of this strategy
      should help maximize the benefit-to-risk ratio of cardiac gene therapy.

PMID- 23955100
TI  - Detection of the prodrug-activating enzyme carboxypeptidase G2 activity with
      chemical exchange saturation transfer magnetic resonance.
AB  - PURPOSE: The purpose of this study is to evaluate if the differential exchange
      rates with bulk water between amine and amide protons can be exploited using
      chemical exchange saturation transfer magnetic resonance (CEST-MR) to monitor the
      release of glutamate induced by carboxypeptidase G2 (CPG2), an enzyme utilized in
      cancer gene therapy. PROCEDURES: Z spectra of solutions of the CPG2 substrate,
      3,5-difluorobenzoyl-L-glutamate (amide), and glutamate (amine) were acquired at
      11.7 T, 37  degrees C, across different pH (5-8). The ability of CEST-MR to
      monitor CPG2-mediated release of glutamate was assessed in extracts of CPG2
      expressing cancer cells and purified solution of CPG2. RESULTS: The addition of
      CPG2 to a solution containing 3,5-difluorobenzoyl-L-glutamate led to a marked and
      progressively increasing CEST effect (+3 ppm), concomitant with the time
      dependent release of glutamate induced by CPG2. CONCLUSION: CEST-MR allows the
      detection of CPG2 activity in vitro and supports the translation of CEST-MRI to
      assess CPG2-based gene therapy in vivo.

PMID- 23955102
TI  - Hemifield or hemispace: what accounts for the ipsilateral advantages in visually
      guided aiming?
AB  - Aiming movements to targets presented on the same side as the reaching limb are
      faster and more accurate than movements made across the body. These advantages
      are typically attributed to within-hemisphere sensorimotor control. However,
      contrary to the within- versus between-hemisphere model, we have shown that some
      of these advantages tend to go with the side of the movement, rather than the
      side of the target (Carey et al. Exp Brain Res 112:496-504, 1996; Carey and Otto
      de Haart Neuropsychologia 39:894, 2001). Barthelemy and Boulinghez (Exp Brain Res
      147:305-312, 2002) acknowledge that our biomechanical account fits data for post
      onset movement parameters such as peak velocity and duration, yet they report
      evidence for some within- versus between-hemisphere contributions to reaction
      time (RT) advantages. To examine a possible difference between early and late
      movement kinematics fitting these alternative models, we have dissociated field
      and space in a different way, which required arm movements with differential
      inertial consequences, as well as unpredictability of target location in terms of
      visual field. The data suggest that visual field may contribute some of the
      variance to hemispatial effects, but only for the right hand. In a second
      experiment, we used an antipointing task to examine hemispatial versus visual
      field effects on RTs and to revisit the possible hand difference identified in
      experiment 1. We found that hemispace accounted for all of the ipsilateral
      advantages, including RT, for both right and left hands. Results are discussed in
      terms of the computational requirements of eye-hand coordination in relative
      unconstrained conditions. 

PMID- 23955103
TI  - Athletes and novices are differently capable to recognize feint and non-feint
      actions.
AB  - Fast motor reactions in sports often require the ability to predict the intended
      action of an opponent as early as possible. Therefore, the present paper
      investigates whether beach volleyball athletes are able to recognize different
      attack hits (i.e. smash vs. poke shot) at an earlier stage of the movement than
      novices. Beach volleyball athletes and novices took part in a response priming
      experiment (Experiment 1). Participants had to decide whether a presented target
      picture depicts a smash or a poke shot. Importantly, the preceding prime pictures
      were taken from different stages of the movements varying between the jump
      (beginning of the movements) and the hand-ball contact (end of the movements).
      Diverging response congruency effects was found for athletes and novices.
      Athletes were able to recognize at an earlier movement stage than novices which
      kind of attack hit was shown at the prime picture. It is suggested that athletes
      might implicitly read movement-related patterns in the depicted athlete's body
      posture (e.g. the angle of the elbow). In contrast, novices might use information
      which is easier to access (e.g. hand-ball relation). In a second experiment,
      novice participants received a visual training to test for a potential perceptual
      source of the priming effects. Notably, participants did not improve their
      ability to differentiate the volleyball techniques, indicating that a better
      recognition performance in athletes is based on motor and not on perceptual
      expertise. 

PMID- 23955101
TI  - Empathy and contextual social cognition.
AB  - Empathy is a highly flexible and adaptive process that allows for the interplay
      of prosocial behavior in many different social contexts. Empathy appears to be a
      very situated cognitive process, embedded with specific contextual cues that
      trigger different automatic and controlled responses. In this review, we
      summarize relevant evidence regarding social context modulation of empathy for
      pain. Several contextual factors, such as stimulus reality and personal
      experience, affectively link with other factors, emotional cues, threat
      information, group membership, and attitudes toward others to influence the
      affective, sensorimotor, and cognitive processing of empathy. Thus, we propose
      that the frontoinsular-temporal network, the so-called social context network
      model (SCNM), is recruited during the contextual processing of empathy. This
      network would (1) update the contextual cues and use them to construct fast
      predictions (frontal regions), (2) coordinate the internal (body) and external
      milieus (insula), and (3) consolidate the context-target associative learning of
      empathic processes (temporal sites). Furthermore, we propose these context
      dependent effects of empathy in the framework of the frontoinsular-temporal
      network and examine the behavioral and neural evidence of three neuropsychiatric
      conditions (Asperger syndrome, schizophrenia, and the behavioral variant of
      frontotemporal dementia), which simultaneously present with empathy and
      contextual integration impairments. We suggest potential advantages of a situated
      approach to empathy in the assessment of these neuropsychiatric disorders, as
      well as their relationship with the SCNM. 

PMID- 23955104
TI  - Mice move smoothly: irrelevant object variation affects perception, but not
      computer mouse actions.
AB  - Human-Computer Interactions pose special demands on the motor system, especially
      regarding the virtual tool transformations underlying typical mouse movements. We
      investigated whether such virtual tool-transformed movements are similarly
      resistant to irrelevant variation of a target object as skilled natural movements
      are. Results show that such irrelevant information deteriorates performance in
      perceptual tasks, whereas movement parameters remain unaffected, suggesting that
      the control of virtual tools draws on the same mechanisms as natural actions do.
      The results are discussed in terms of their practical utility and recent findings
      investigating unskilled and transformed movements in the framework of the
      action/perception model and the integration of tools into the body schema. 

PMID- 23955106
TI  - The effect of a first-generation H1-antihistamine on postural control: a
      preliminary study in healthy volunteers.
AB  - First-generation H1-antihistamines are known to cause fatigue and drowsiness, due
      to their poor receptor selectivity and their high penetration rate of the blood
      brain barrier. However, little is known about the effects of first-generation H1
      antihistamines on postural stability. The purpose of this study was to evaluate
      the effects of d-chlorpheniramine on postural stability using posturography with
      and without foam rubber. A double-blind study with three parallel groups was
      conducted. Twenty-seven healthy young volunteers (mean age 21.9 years) were
      recruited and orally administered d-chlorpheniramine, 2 or 4 mg, or placebo.
      Postural sway was measured every hour up to 8 h after administration. Two-legged
      stance tasks were performed by each subject in four conditions: eyes open or eyes
      closed and with or without foam rubber. Inter-group comparisons showed that the
      group receiving 4-mg d-chlorpheniramine showed significantly larger sway in the
      eyes open with foam rubber condition (visual and vestibular information
      available, somatosensory information reduced). Inter-subject analysis in the 4-mg
      d-chlorpheniramine group showed that the effect of d-chlorpheniramine on postural
      control was variable. Our results suggest that among the three main sensory
      systems responsible for postural control (visual, vestibular, and somatosensory),
      d-chlorpheniramine may have a larger effect on the visual and/or vestibular
      systems in susceptible individuals. 

PMID- 23955107
TI  - Mechanical allodynia in human glabrous skin mediated by low-threshold cutaneous
      mechanoreceptors with unmyelinated fibres.
AB  - We recently showed that C-tactile fibres (CTs) in human hairy skin (anterior leg)
      mediate crossover between innocuous touch and noxious touch, i.e. mechanical
      allodynia. Although there is no evidence for existence of a phenotypically
      identical class of CTs in human glabrous skin, the 'qualia' of affective stimuli
      are comparable across skin types. In 42 healthy subjects, muscle pain was induced
      by infusing hypertonic saline (5 %) into flexor carpi ulnaris muscle.
      Concurrently, sinusoidal vibration (200 Hz-200 MUm) was applied to glabrous skin
      of little finger. The neural substrate of allodynia was determined by employing
      conduction blocks of myelinated (ulnar nerve compression) and unmyelinated (low
      dose intra-dermal anaesthesia) fibres. In order to compare the expression of
      allodynia across spinal segments and skin types, vibration was also applied to
      glabrous skin of index finger and hairy skin of dorsal forearm. In addition, high
      precision brushing stimuli were applied at speeds of 1.0 and 3.0 cm s(-1) to
      digital glabrous skin with absent myelinated fibres. During muscle pain,
      vibration caused a significant and reproducible increase in pain (allodynia).
      This effect persisted during blockade of myelinated fibres, but was abolished by
      inactivation of unmyelinated cutaneous fibres. The vibration-evoked effects were
      found to be comparable across spinal segments and skin types. Furthermore,
      brushing produced a near-identical expression of C-fibre-mediated allodynia.
      Prior to induction and upon cessation of muscle pain, vibration and brushing were
      reported as non-painful. Based on these results, we postulate that a functional
      homologue of the CTs (hairy skin) mediates allodynia in human glabrous skin.

PMID- 23955109
TI  - New water soluble terphenylene diethynylene fluorophores.
AB  - Inspired by our earlier works on sensors from dendritic phenyleneethynylenes, two
      new star-shaped water-soluble fluorophores containing terphenylene diethynylene
      units and anionic carboxylate peripheries are successfully synthesized. The
      convergent synthesis relies on Sonogashira cross-coupling reactions between tris
      (4-ethynylphenyl)amine and the iodophenyleneethynylene branches. All of the
      compounds are characterized by (1)H, (13)C NMR, and mass spectrometry. In aqueous
      solution, the less polar fluorophore 1 shows lower quantum yield than 2 (18 vs
      33%) as a result of hydrophobic induced aggregation. One of these anionic water
      soluble fluorophores exhibits a selective fluorescence quenching by Fe(3+) ion in
      phosphate buffer pH 8.

PMID- 23955110
TI  - Structural investigation and photoluminescent properties of gadolinium(III),
      europium(III) and terbium(III) 3-mercaptopropionate complexes.
AB  - This work reports on the synthesis, crystallographic determination and
      spectroscopic characterization of gadolinium(III), terbium(III) and europium(III)
      3-mercaptopropionate complexes, aqua-tris(3-mercaptopropionate)lanthanide(III)-
      [Ln(mpa)3(H2O)]. The Judd-Ofelt intensity parameters were experimentally
      determined from emission spectrum of the [Eu(mpa)3(H2O)]complex and they were
      also calculated from crystallographic data. The complexes are coordination
      polymers, where the units of each complex are linked together by carboxylate
      groups leading to an unidimensional and parallel chains that by chemical
      interactions form a tridimensional framework. The emission spectrum profile of
      the [Eu(mpa)3(H2O)] complex is discussed based on point symmetry of the
      europium(III) ion, that explains the bands splitting observed in its emission
      spectrum. Photoluminescent analysis of the [Gd(mpa)3(H2O)] complex show no
      efficient ligand excitation but an intense charge transfer band. The excitation
      spectra of the [Eu(mpa)3(H2O)] and [Tb(mpa)3(H2O)] complexes do not show evidence
      of energy transfer from the ligand to the excited levels of these trivalent ions.
      Therefore the emission bands are originated only by direct f-f
      intraconfigurational excitation of the lantanide(III) ions.

PMID- 23955111
TI  - B-cell function after unrelated umbilical cord blood transplantation using a
      minimal-intensity conditioning regimen in patients with X-SCID.
AB  - Patients with X-linked severe combined immunodeficiency (X-SCID) suffer from
      severe and persistent infections, and usually die early in life unless treated by
      hematopoietic stem cell transplantation. If a patient has an HLA-identical
      sibling donor, preparative conditioning is not necessary for T-cell engraftment
      and B-cell function. However, in the absence of such a donor, long-term
      reconstitution of full B-cell function is often problematic, leading in many
      cases to a lifetime requirement for immunoglobulin replacement therapy.
      Preparative myeloablative conditioning has been shown to improve long-term B-cell
      function, but may aggravate pre-existing infection and transplant-related
      toxicity. It is thus important to determine the minimum intensity of conditioning
      that assures immunoglobulin production. In the present study, we performed
      reduced-intensity conditioning (RIC), consisting of fludarabine 125 mg/m(2) and
      melphalan 80 mg/m(2), prior to unrelated umbilical cord blood transplantation
      (UCBT) for five patients with X-SCID, none of them had an HLA-identical donor.
      Four patients survived more than 4 years without sequelae, and none required long
      term immunoglobulin replacement therapy. One patient succumbed to sepsis in
      conjunction with severe GVHD. Our result demonstrates that the RIC regimen
      described above in combination with UCBT is an effective and less toxic
      conditioning to correct B-cell function in patients with X-SCID. 

PMID- 23955112
TI  - Idiopathic pneumonia syndrome with thrombotic microangiopathy-related changes
      after allogeneic hematopoietic stem cell transplantation.
AB  - Idiopathic pneumonia syndrome (IPS), defined as widespread alveolar injury, is a
      severe complication of hematopoietic stem cell transplantation (HSCT) and a
      clinical syndrome with variable histopathologic correlates and multiple
      etiologies. Transplantation-associated thrombotic microangiopathy (TMA) is
      another severe complication of HSCT. TMA occurs when endothelial injury causes
      thrombosis and fibrin deposition in the organ microcirculation. We present a case
      of IPS with TMA-related changes in the lungs following HSCT. A 54-year-old woman
      underwent an allogeneic HSCT for refractory multiple myeloma. During
      transplantation, cyclosporine was administered for prophylaxis against graft
      versus-host disease, but she developed respiratory failure after she was weaned
      off the drug. A computed tomography scan revealed ground-glass attenuation and
      reticular opacity in the bilateral whole-lung fields. Bronchoscopy indicated no
      evidence of infection, and IPS was diagnosed. High-dose steroids and etanercept
      were ineffective, and she died 1 month after the onset of IPS. Autopsy revealed
      diffuse alveolar damage, and stenosis or obstruction due to intimal thickening
      and thrombi resulting from endothelial injury in the arterioles of both lungs. We
      retrospectively diagnosed TMA based on the histological and clinical findings. To
      our knowledge, this is the first report suggesting the possible role of TMA in
      the clinical course of IPS.

PMID- 23955113
TI  - Meningeal myelomatosis developed after treatment with novel agents.

PMID- 23955114
TI  - Organocatalytic tandem Morita-Baylis-Hillman-Michael reaction for asymmetric
      synthesis of a drug-like oxa-spirocyclic indanone scaffold.
AB  - A novel multicatalytic MBH-Michael tandem reaction has been developed for the
      asymmetric assembly of ninhydrin, nitroolefins and aldehydes into a structurally
      complex oxa-spirocyclic indanone backbone. Successive iodocyclization allowed us
      to convert these multifunctional allylic products into fused chiral natural
      product mimics. 

PMID- 23955115
TI  - Capsaicin inhibits Porphyromonas gingivalis growth, biofilm formation,
      gingivomucosal inflammatory cytokine secretion, and in vitro osteoclastogenesis.
AB  - The prevention and treatment of periodontitis requires not only the control of
      causative pathogens, especially Porphyromonas gingivalis, but also the regulation
      of inflammatory immune response. Investigating auxiliary drugs for periodontitis
      during conventional treatments is, thus, quite important. Capsaicin, an agonist
      for the vanilloid receptor subtype 1 (TRPV1), due to its bacteriostatic activity
      against Gram-negative bacteria and anti-inflammatory effects, appears to be a
      promising drug. In this work, the antimicrobial activity of capsaicin against P.
      gingivalis and biofilm formation, inflammatory cytokine levels in experimental
      periodontitis, osteoclast precursor proliferation, and osteoclastogenesis in
      vitro were fully investigated. The results showed that capsaicin inhibited P.
      gingivalis growth with a minimum inhibitory concentration (MIC) and a minimum
      bactericidal concentration (MBC) of 16 and 64 mg/l, respectively. Capsaicin also
      inhibited P. gingivalis biofilm formation, with minimum biofilm inhibition
      concentrations MBIC50 and MBIC90 of 16 and 32 mg/l, respectively, and reduced pre
      formed biofilms' viability with a minimum biofilm reduction concentration MBRC50
      of 64 mg/l, as demonstrated by confocal laser scanning microscopy. In
      experimental periodontitis, except for IL-10, TNF-alpha, IL-1beta, IL-6, IL-12,
      and iNOS were depressed after capsaicin treatment. Moreover, capsaicin also
      suppressed osteoclast precursor proliferation and osteoclastogenesis, as
      demonstrated by NF-KB p65. However, this favorable effect was attenuated by the
      TRPV1 antagonist, camphor. It, thus, suggests that capsaicin is a potential drug
      for the auxiliary treatment of periodontitis. TRPV1 activation may involve in
      beneficial roles of capsaicin on periodontitis.

PMID- 23955116
TI  - Wogonin induces apoptosis by suppressing E6 and E7 expressions and activating
      intrinsic signaling pathways in HPV-16 cervical cancer cells.
AB  - Wogonin is a flavonoid compound extracted from Scutellaria baicalensis and is
      well known as a benzodiazepine receptor ligand with anxiolytic effects. Many
      recent studies have demonstrated that wogonin modulates angiogenesis,
      proliferation, invasion, and tumor progress in various cancer tissues. We further
      explored the mechanism of action of wogonin on cervical cancer cells that contain
      or lack human papillomavirus (HPV) DNA. Wogonin was cytotoxic to HPV 16 (+)
      cervical cancer cells, SiHa and CaSki, but not to HPV-negative cells. We
      demonstrated that wogonin induced apoptosis by suppressing the expressions of the
      E6 and E7 viral oncogenes in HPV-infected cervical cancer CaSki and SiHa cells.
      The modulation of p53 and protein retinoblastoma (pRb) were also triggered by the
      suppression of E6 and E7 expressions. However, p53 was not altered in HPV
      negative cervical cancer C33A cells. Moreover, wogonin modulated the
      mitochondrial membrane potential and the expression of pro- and anti-apoptotic
      factors such as Bax and Bcl-2. Wogonin also provoked the cleavage of caspase-3,
      caspase-9, and poly ADP ribose polymerase. After transfection of siRNAs to target
      E6 and E7, additional restoration of p53 and pRb was not induced, but processing
      of caspases and PARP was increased compared with wogonin treatment alone.
      Together, our findings demonstrated that wogonin effectively promotes apoptosis
      by downregulating E6 and E7 expressions and promoting intrinsic apoptosis in
      human cervical cancer cells. 

PMID- 23955117
TI  - Al3+-induced far-red fluorescence enhancement of conjugated polymer nanoparticles
      and its application in live cell imaging.
AB  - Fluorescent nanoparticles (NPs) for Al(3+) sensing with high selectivity were
      developed from a type of carbazole-based conjugated polymer with a two
      dimensional donor-pi bridge-acceptor (D-pi-A) structure. These NPs are
      characterized by their small particle diameter (~18 nm), far-red fluorescence
      emission (centered ~710 nm), and Al(3+)-induced fluorescence enhancement with
      high selectivity owing to an Al(3+)-triggered inhibition on the intramolecular
      charge transfer (ICT) processes between the conjugated backbone and the pendant
      acceptors. This type of nanoparticle is easily suspended in aqueous solutions,
      indicating their practical applicability in physiological media, and their
      ability for intracellular Al(3+) sensing was confirmed. As compared to other
      types of conjugated polymer based probes showing metal ion mediated fluorescence
      quenching, these as-prepared NPs possess analyte-enhanced fluorescence emission,
      which is analytically favored in terms of sensitivity and selectivity.
      Fluorescence emission with wavelengths in the biological window of maximum
      optical transparency (~700 to 1000 nm) is expected to impart a salient advantage
      for biological detection applications to these as-prepared probes. The superior
      features of merit of this new type of fluorescent probe, together with the
      validation of practicability for intracellular Al(3+) ion sensing, are indicative
      of their potential for application in fluorescence-based imaging and sensing,
      such as investigations on Al(3+)-related physiological and pathological
      processes. 

PMID- 23955119
TI  - Carcinoid valve disease.
AB  - OPINION STATEMENT: Carcinoid is a rare neuroendocrine tumor that typically
      originates in the gastrointestinal tract and can result in a constellation of
      symptoms, mediated by vasoactive substances, referred to as carcinoid syndrome.
      Carcinoid valve and heart disease is characterized by the plaque-like,
      endocardial fibrous tissue deposits, primarily affecting the right heart
      endocardium and valves, which result as a consequence of the disease process.
      Potential mechanisms for the carcinoid valve disease include the complex role of
      excess serotonin and its interaction with serotonin receptors and transporters.
      Carcinoid valve and heart disease is a frequent occurrence in patients with
      carcinoid syndrome and is accountable for substantial morbidity and mortality.
      Cardiac surgery remains the most effective treatment option for carcinoid valve
      disease and a multidisciplinary approach at an experienced center is recommended
      for patients with metastatic carcinoid and carcinoid heart disease.

PMID- 23955120
TI  - Atmospheric photolytic reduction of Hg(ii) in dry aerosols.
AB  - A laboratory reactor system was developed to examine the role of light and
      aerosol composition in the reduction of oxidized mercury (Hg(ii)) in laboratory
      generated aerosols. Aerosolized sodium chloride, doped with mercury chloride, was
      exposed to light in a fixed-bed flow-through reactor. Three spectral ranges (UV,
      visible and a simulated solar spectrum) were examined, along with dark
      experiments, to investigate the role of light conditions in mercury reduction. In
      addition, the role of iron in the aerosol matrix was examined. The effluent from
      the reactor was analyzed for Hg(0) as evidence of reduction of Hg(ii) in the
      reactor. Significant reduction of Hg(ii) (1.5-9.9%) was observed for all three
      light sources and the rate of mercury reduction was proportional to the light
      irradiance. The presence of iron in the aerosol matrix inhibited the reduction
      rate and the degree of inhibition was dependent on the chemical form of the iron
      in the aerosol. The observed reduction reactions may be important chemical
      processes in the atmosphere and could be incorporated in atmospheric transport
      models that are used to understand the fate of atmospheric mercury. 

PMID- 23955118
TI  - Toll-like receptor 4 activation in Barrett's esophagus results in a strong
      increase in COX-2 expression.
AB  - BACKGROUND: Barrett's esophagus (BE) is known to progress to esophageal
      adenocarcinoma in a setting of chronic inflammation. Toll-like receptor (TLR) 4
      has been linked to inflammation-associated carcinogenesis. We aimed to determine
      the expression and functional activity of TLR4 in the esophagus and whether TLR4
      activation in BE could promote carcinogenesis by inducing COX-2 expression.
      METHODS: TLR4 expression in esophageal adenocarcinoma, BE, duodenum, reflux
      esophagitis and normal squamous esophagus biopsies was assessed using real-time
      PCR and validated by in situ hybridization and immunohistochemistry. Ex vivo
      cultures of BE, duodenum and normal squamous esophagus biopsies and a BE cell
      line (BAR-T) were stimulated with the TLR4 agonist lipopolysaccharide (LPS). To
      evaluate the effect of TLR4 activation, NF-kappaB activation, IL8 secretion and
      expression and COX-2 expression were determined. RESULTS: TLR4 expression was
      significantly increased in esophageal adenocarcinoma, BE, duodenum and reflux
      esophagitis compared to normal squamous esophagus. LPS stimulation resulted in NF
      kappaB activation and a dose-dependent increase of IL8 secretion and mRNA
      expression. The induction of IL8 was more evident in BE compared to normal
      squamous esophagus. Upon LPS stimulation, COX-2 expression increased
      significantly in ex vivo cultured BE biopsies, which was observed in both
      epithelium and lamina propria cells. However, no effect was found in duodenum and
      normal squamous esophagus biopsies. CONCLUSION: TLR4 activation in BE results in
      a strong increase in COX-2 and may contribute to malignant transformation.

PMID- 23955121
TI  - Autophagic flux and oxidative capacity of skeletal muscles during acute
      starvation.
AB  - Autophagy is an important proteolytic pathway in skeletal muscles. The roles of
      muscle fiber type composition and oxidative capacity remain unknown in relation
      to autophagy. The diaphragm (DIA) is a fast-twitch muscle fiber with high
      oxidative capacity, the tibialis anterior (TA) muscle is a fast-twitch muscle
      fiber with low oxidative capacity, and the soleus muscle (SOL) is a slow-twitch
      muscle with high oxidative capacity. We hypothesized that oxidative capacity is a
      major determinant of autophagy in skeletal muscles. Following acute (24 h)
      starvation of adult C57/Bl6 mice, each muscle was assessed for autophagy and
      compared with controls. Autophagy was measured by monitoring autophagic flux
      following leupeptin (20 mg/kg) or colchicine (0.4 mg/kg/day) injection. Oxidative
      capacity was measured by monitoring citrate synthase activity. In control mice,
      autophagic flux values were significantly greater in the TA than in the DIA and
      SOL. In acutely starved mice, autophagic flux increased, most markedly in the TA,
      and several key autophagy-related genes were significantly induced. In both
      control and starved mice, there was a negative linear correlation of autophagic
      flux with citrate synthase activity. Starvation significantly induced AMPK
      phosphorylation and inhibited AKT and RPS6KB1 phosphorylation, again most
      markedly in the TA. Starvation induced Foxo1, Foxo3, and Foxo4 expression and
      attenuated the phosphorylation of their gene products. We conclude that both
      basal and starvation-induced autophagic flux are greater in skeletal muscles with
      low oxidative capacity as compared with those with high oxidative capacity and
      that this difference is mediated through selective activation of the AMPK pathway
      and inhibition of the AKT-MTOR pathways. 

PMID- 23955122
TI  - Mental chronometry and individual differences: modeling reliabilities and
      correlations of reaction time means and effect sizes.
AB  - We used a general stage-based model of reaction time (RT) to investigate the
      psychometric properties of mean RTs and experimental effect sizes (i.e.,
      differences in mean RTs). Using the model, formulas were derived for the
      reliabilities of mean RTs and RT difference scores, and these formulas provide
      guidance about the number of trials per participant needed to obtain reliable
      estimates of these measures. In addition, formulas were derived for various
      different types of correlations computed in RT research (e.g., correlations
      between a mean RT and an external non-RT measure, between two mean RTs, between a
      mean RT and an RT effect size). The analysis revealed that observed RT-based
      correlations depend on many parameters of the underlying processes contributing
      to RT. We conclude that these correlations often fail to support the inferences
      drawn from them and that their proper interpretation is far more complex than is
      generally acknowledged. 

PMID- 23955123
TI  - The ACMSD gene, involved in tryptophan metabolism, is mutated in a family with
      cortical myoclonus, epilepsy, and parkinsonism.
AB  - Familial cortical myoclonic tremor and epilepsy is a phenotypically and
      genetically heterogeneous autosomal dominant disorder characterized by the
      presence of cortical myoclonic tremor and epilepsy that is often accompanied by
      additional neurological features. Despite the numerous familial studies performed
      and the number of loci identified, there is no gene associated with this
      syndrome. It is expected that through the application of novel genomic
      technologies, such as whole exome sequencing and whole genome sequencing, a
      substantial number of novel genes will come to light in the coming years. In this
      study, we describe the identification of two disease-segregating mutations in a
      large family featuring cortical myoclonic tremor with epilepsy and parkinsonism.
      Due to the previous association of ACMSD deficiency with the development of
      epileptic seizures, we concluded that the identified nonsense mutation in the
      ACMSD gene, which encodes for a critical enzyme of the kynurenine pathway of the
      tryptophan metabolism, is the disease-segregating mutation most likely to be
      responsible for the phenotype described in our family. This finding not only
      reveals the identification of the first gene associated with familial cortical
      myoclonic tremor and epilepsy but also discloses the kynurenine pathway as a
      potential therapeutic target for the treatment of this devastating syndrome. KEY
      MESSAGE: ACMSD is mutated in a family with cortical myoclonus, epilepsy, and
      parkinsonism. ACMSD mutation contributes to the development of FCMTE QA
      accumulation is likely to play an important role in the pathogenesis of FCMTE.
      The kynurenine pathway as a potential drug target for the treatment of epilepsy.

PMID- 23955124
TI  - Pre-enlistment hearing loss and hearing loss disability among US soldiers and
      marines.
AB  - Hearing loss is a common condition among US adults, with some evidence of
      increasing prevalence in young adults. Noise-induced hearing loss attributable to
      employment is a significant source of preventable morbidity world-wide. The US
      military population is largely comprised of young adult males serving in a wide
      variety of occupations, many in high noise-level conditions, at least
      episodically. To identify accession and service-related risk factors for hearing
      related disability, matched case-control study of US military personnel was
      conducted. Individuals evaluated for hearing loss disability in the US Army and
      Marine Corps were frequency matched to controls without history of disability
      evaluation on service and enlistment year. Conditional logistic regression was
      used to examine the association between accession and service-related factors and
      hearing-related disability evaluations between October 2002 and September 2010.
      Individuals with medically disqualifying audiograms or hearing loss diagnoses at
      application for military service were 8 and 4 times more likely, respectively, to
      have a disability evaluation related to hearing loss, after controlling for
      relevant accession, demographic, and service-related factors. Conservative
      hearing loss thresholds on pre-enlistment audiograms, stricter hearing loss
      medical waiver policies or qualified baseline audiograms pre-enlistment are
      needed in the U.S military. Industrial corporations or labor unions may also
      benefit from identifying individuals with moderate hearing loss at the time of
      employment to ensure use of personal protective equipment and engineer controls
      of noise. 

PMID- 23955125
TI  - Portable music player users: cultural differences and potential dangers.
AB  - Many studies have examined the use of portable music players portable listening
      devices (PLDs) from various ethnic groups. Some findings suggest that there may
      be differences among ethnic groups that lead to louder or longer listening when
      using PLD devices. For example, some studies found that Hispanic PLD users listen
      at higher volume levels while other studies found that African American PLD users
      listen at higher volume levels. No investigator has explained the reasons for
      differences among ethnic groups in listening intensity. This paper will address
      the possible reasons for these differences and offer guidelines for the
      prevention of noise-induced hearing loss. 

PMID- 23955126
TI  - Annoyance evaluation and the effect of noise on the health of bus drivers.
AB  - In the present study, we evaluated annoyance and the effects of noise on the
      health of bus drivers. For that, 200 bus drivers from a public transport company
      participated in a cross-sectional study. Annoyance and effects on health was
      measured with analog scale: Sleep quality, occurrence of tinnitus, headache,
      irritation, and annoyance from bus engine, traffic, and passengers. Data of age
      and working time of bus drivers also were obtained. For noise exposure, LA eq was
      evaluated in 80 buses. Statistical analysis consisted of mean, standard
      deviation, minimum, and maximum, Kruskal-Wallis test with post-hoc Dunn, one-way
      ANOVA with post-hoc Tukey and Spearman's correlation coefficient. Results
      indicate three groups of bus drivers (not annoyed: (N.A.), a little annoyed
      (L.A.) and highly annoyed (H.A.)). The group H.A. was younger and with less
      working time in relation to others, with a significant difference only for age.
      Regarding sleep quality, there was no significant difference. For results on the
      occurrence of tinnitus, headache and irritation after work, group H.A. had
      significantly higher means. Result of annoyance to the bus engine was
      significantly higher in H.A. than in L.A. and N.A. Annoyance to traffic and
      passengers, no significant differences were found, but the highest results were
      found for L.A., followed by H.A. and N.A. Equivalent sound pressure level in
      buses was above of the limit for occupational comfort. It was concluded that bus
      drivers has considerable level of noise annoyance and some health effects are
      perceived. The noise is a factor discomfort ergonomic that may cause effects on
      health of bus drivers. This study aims to evaluate annoyance and the effects of
      noise on the health of bus drivers. Cross-sectional study with buses and bus
      drivers. For that, 200 bus drivers from a public transport company participated
      in a cross-sectional study. Annoyance and effects on health was measured with
      analog scale: Sleep quality, occurrence of tinnitus, headache, irritation and
      annoyance from bus engine, traffic, and passengers. Data of age and working time
      of bus drivers also were obtained. For noise exposure, LA eq was evaluated in 80
      buses. Statistical analysis consisted of mean, standard deviation, minimum and
      maximum, Kruskal-Wallis test with post-hoc Dunn, one-way ANOVA with post-hoc
      Tukey and Spearman's correlation coefficient. Results indicate three groups of
      bus drivers (N.A., a L.A. and H.A.). The group H.A. was younger and with less
      working time in relation to others, with a significant difference only for age.
      Regarding sleep quality, there was no significant difference. For results on the
      occurrence of tinnitus, headache and irritation after work, group H.A. had
      significantly higher means. Result of annoyance to the bus engine was
      significantly higher in H.A. than in L.A. and N.A. Annoyance to traffic and
      passengers, no significant differences were found, but the highest results were
      found for L.A., followed by H.A. and N.A. Equivalent sound pressure level in
      buses was above of the limit for occupational comfort. It was concluded that bus
      drivers has considerable level of noise annoyance and some health effects are
      perceived. 

PMID- 23955127
TI  - Direct effects of music in non-auditory cells in culture.
AB  - The biological effects of electromagnetic waves are widely studied, especially
      due to their harmful effects, such as radiation-induced cancer and to their
      application in diagnosis and therapy. However, the biological effects of sound,
      another physical agent to which we are frequently exposed have been considerably
      disregarded by the scientific community. Although a number of studies suggest
      that emotions evoked by music may be useful in medical care, alleviating stress
      and nociception in patients undergoing surgical procedures as well as in cancer
      and burned patients, little is known about the mechanisms by which these effects
      occur. It is generally accepted that the mechanosensory hair cells in the ear
      transduce the sound-induced mechanical vibrations into neural impulses, which are
      interpreted by the brain and evoke the emotional effects. In the last decade;
      however, several studies suggest that the response to music is even more complex.
      Moreover, recent evidence comes out that cell types other than auditory hair
      cells could response to audible sound. However, what is actually sensed by the
      hair cells, and possible by other cells in our organism, are physical differences
      in fluid pressure induced by the sound waves. Therefore, there is no reasonable
      impediment for any cell type of our body to respond to a pure sound or to music.
      Hence, the aim of the present study was to evaluate the response of a human
      breast cancer cell line, MCF7, to music. The results' obtained suggest that music
      can alter cellular morpho-functional parameters, such as cell size and
      granularity in cultured cells. Moreover, our results suggest for the 1 st time
      that music can directly interfere with hormone binding to their targets,
      suggesting that music or audible sounds could modulate physiological and
      pathophysiological processes. 

PMID- 23955128
TI  - Distortion product otoacoustic emission level maps from normal and noise-damaged
      cochleae.
AB  - Distortion product otoacoustic emission (DPOAE) level mapping may be useful for
      detecting noise-induced hearing loss (NIHL) early. Employing DPOAE mapping
      effectively requires knowledge of the optimal mapping parameters to use for
      detecting noise-induced changes. The goal of this project was to show the map
      regions that differ most between normal and noise-damaged cochlea to determine
      the optimal mapping parameters for detecting NIHL. DPOAE level maps were
      generated for the 2f 1 -f 2 and the 2f 2 -f 1 DPOAEs for 17 normal hearing male
      subjects and 19 male subjects with NIHL. DPOAEs were measured in DPOAE frequency
      steps of approximately 44 Hz from 0.5 kHz to 6 kHz using constant f 2 /f 1 ratios
      incremented in 0.025 steps from 1.025 to 1.5 using both unequal-level (L1,L2 =
      65,55 dB sound pressure level (SPL)) and equi-level (L1,L2 = 75,75 dB SPL)
      stimulus paradigms. Maximal responses for the 2f 2 -f 1 emission at L1,L2 = 65,55
      dB SPL were found at lower ratios compared to previous studies. The map regions
      where NIHL eliminated or reduced DPOAE magnitude were identified. DPOAE level
      mapping using higher-level, equi-level primaries produced significantly more
      detectable emissions particularly for the 2f 2 -f 1 emission. The data from this
      study can be used to optimize DPOAE level mapping parameters for tracking noise
      exposed subjects longitudinally. 

PMID- 23955129
TI  - The epidemiology of noise exposure in the Australian workforce.
AB  - This work considers an alternate methodology for the estimation of the noise
      exposed population of the Australian workforce. Previous methods relied on the
      statistics from the annual rate of application for worker's hearing loss
      compensation claims, the generalization of small scale surveys to the broader
      population or larger scale telephone surveys. This proposed method takes measured
      noise exposure data from sampled industries and combines that with official
      demographic information on the numbers employed in the respective industries.
      From the Australian data, it is estimated that around 20.1% of the workforce
      regularly work in noise above the recommended exposure standard (L Aeq, 8 h = 85
      dB) and 9.4% above and exposure of 90 dB. These figure lie within the range of
      estimates derived from other methodologies. 

PMID- 23955130
TI  - Awakening effects of church bell noise: geographical extrapolation of the results
      of a polysomnographic field study 1.
AB  - Based on a previously published exposure-effect model of Electroencephalography
      (EEG)-awakening reactions (AWR) due to nightly church bell noise events, as well
      as on geocoded building and population data, we estimated the total number of the
      church bell noise induced awakenings on the population of the Canton of Zurich,
      in Switzerland. The calculated mean number of EEG awakenings per person in the
      studied region, triggered by church bell ringing, varied between 0 and about 5.5
      per night. The results suggest that up to 120-150 m distance from churches, on
      average more than one additional EEG awakening occurs per night per person. An
      estimated 2.5-3.5 percent of the population in the Canton of Zurich experiences
      at least one additional awakening per night due to church bell noise. To provide
      a simple decision support tool for authorities that consider limiting bell
      ringing in the night in some form, we simulated different scenarios to estimate
      the effects of different sound attenuation measures at the belfry as well as the
      effects of different lengths and positions of nocturnal bell ringing suspension
      periods. The number of awakenings could be reduced by more than 99 percent by,
      for example, suspending church bell ringing between midnight and 06 h in the
      morning. A reduction of the number of AWRs of about 75 percent could be achieved
      by reducing the sound-pressure levels of bells by 5 dB. 

PMID- 23955131
TI  - Road traffic noise exposure and annoyance: a cross-sectional study among adult
      Indian population.
AB  - Preceding research has linked noise exposure, road traffic bring the dominant
      community source, with annoyance, which is an indicator of more serious, chronic
      health conditions. This study aimed to explore the association between
      residential road traffic noise and self-reported annoyance from an adult Indian
      population, residing close to roadways. The cross-sectional study used a
      questionnaire survey in an urban Indian municipality along roadways, where
      faetaade noise assessment was made manually. The survey included randomly
      selected subjects aged 19-59 years, residing minimum of 10 years in the area and
      residing within 50 m of the roadways. Association of self-reported annoyance and
      noise exposure was examined by binary and multiple logistic regressions. The
      noise exposure was classified in units of 5 dB (A) from <65 dB (A) to 80 dB (A).
      Self-reported annoyance was marked at levels above 65-70 dB (A). A 67.5 dB (AA)
      is suggested as a threshold level. The association was statistically significant
      for female subjects with the adjusted odds ratio being 2.35 (95% confidence
      intervals: 0.99-5.58). Prevalence of annoyance was more for male subjects. Both
      age and period of residence were significant predictors of annoyance. Vulnerable
      age sub-groups were 34-40 years, followed by 50-60 years. The results of this
      study further suggest the association residential noise exposure near roadways
      and self-reported annoyance, among the study subjects. 

PMID- 23955132
TI  - Adolescents' reported hearing symptoms and attitudes toward loud music.
AB  - The aim of the present study was to compare the adolescents' attitudes toward
      loud music in relation to a set of self-perceived auditory symptoms and
      psychological variables such as norms, preparedness to take risks and risk
      judgment in noisy situations. A questionnaire on hearing and preventive behavior
      was distributed to 281 upper secondary school students aged 15-19 years. The
      questionnaire included youth attitude to noise scale, questions about perceived
      hearing symptoms such as tinnitus and sound sensitivity and finally statements on
      perceived behavioral norms regarding hearing protection use, risk-taking and risk
      judgment in noisy settings. Self-perceived auditory symptoms such as sound
      sensitivity and permanent tinnitus had a significant relationship with less
      tolerant attitudes toward loud music. Permanent tinnitus and sound sensitivity
      together accounted for 15.9% of the variation in attitudes toward loud music.
      Together with the psychological variables norms, preparedness to take risks and
      risk-judgment 48.0% of the variation in attitudes could be explained. Although
      perceived hearing symptoms (sound sensitivity and permanent tinnitus) was
      associated with less tolerant attitudes toward loud music, psychological
      variables such as norms, preparedness to take risks and risk-judgment were found
      to be more strongly associated with attitudes toward loud music and should
      therefore be considered more in future preventive work. Health promotive
      strategies should focus on changing not merely individual attitudes, but also
      societal norms and regulations in order to decrease noise induced auditory
      symptoms among adolescents. 

PMID- 23955133
TI  - Patterns of physiological and affective responses to vehicle pass-by noises.
AB  - Traffic noise is considered causing annoyance and severe health effects like
      cardiovascular disease (CVD). The present laboratory study examines the
      importance of individual factors, namely age, gender and personality traits on
      short term physiological and affective response to vehicle pass-by noises. Four
      groups of subjects (20-30 vs. 40-55 year-old male or female, n = 66 in total)
      were exposed to a series of vehicle pass-by noises. Physiological responses
      (finger-pulse amplitude [FPA], skin conductance level [SCL]) were registered
      during the exposure; affective responses and judgements regarding the sounds were
      assessed by questionnaires. Noise sensitivity and sensation seeking were measured
      by validated questionnaires. The results show different patterns of response
      depending on age, gender and personality. The strongest sympathetic stress
      reaction as measured by SCL was found for the older female group. In regression
      analysis, the SCL response was predicted by the female gender and low score of
      sensation seeking only (adjusted R2 = 0.139). The FPA response was strongest
      among the young men and age was the only significant predictor. For affective
      responses of pleasantness and activation, regression analysis proved noise
      sensitivity and sensation seeking to be significant predictors (adjusted R2 =
      0.187 respectively 0.154). Age, gender and personality influence physiological
      and affective reactions to traffic noise, which might affect health conditions.
      Especially, a potential risk of older women for CVD owing to noise should be
      investigated further. Individual sensitiveness in terms of noise sensitivity or
      sensation seeking proves to be important for explaining differences in response
      to noise. 

PMID- 23955134
TI  - Using the effect of alcohol as a comparison to illustrate the detrimental effects
      of noise on performance.
AB  - The aim of the present research is to provide a user-friendly index of the
      relative impairment associated with noise in the aircraft cabin. As such, the
      relative effect of noise, at a level typical of an aircraft cabin was compared
      with varying levels of alcohol intoxication in the same subjects. Since the
      detrimental effect of noise is more pronounced on non-native speakers, both
      native English and non-native English speakers featured in the study. Noise
      cancelling headphones were also tested as a simple countermeasure to mitigate the
      effect of noise on performance. A total of 32 participants, half of which were
      non-native English speakers, completed a cued recall task in two alcohol
      conditions (blood alcohol concentration 0.05 and 0.10) and two audio conditions
      (audio played through the speaker and noise cancelling headphones). The results
      revealed that aircraft noise at 65 dB (A) negatively affected performance to a
      level comparable to alcohol intoxication of 0.10. The results also supported
      previous research that reflects positively on the benefits of noise cancelling
      headphones in reducing the effects of noise on performance especially for non
      native English speakers. These findings provide for personnel involved in the
      aviation industry, a user-friendly index of the relative impairment associated
      with noise in the aircraft cabin as compared with the effects of alcohol. They
      also highlight the benefits of a simple countermeasure such as noise cancelling
      headphones in mitigating some of the detrimental effects of noise on performance.

PMID- 23955135
TI  - [Prof. Dr. med. Guido Gerken].

PMID- 23955136
TI  - [Editorial - invitation to the congress of visceral medicine 2013 in Nurnberg].

PMID- 23955137
TI  - Is there a role for capsule endoscopy in the staging work-up of patients with
      gastric marginal zone B-cell lymphoma of MALT?
AB  - INTRODUCTION: In earlier studies, involvement of the small intestine was reported
      in patients with gastrointestinal lymphoma. Prospective data on the involvement
      of the small intestine in patients suffering from gastric extranodal MZBCL of
      MALT do not exist so far. In this study, we investigated the frequency of the
      involvement of the small intestine and the role of capsule endoscopy in patients
      with gastrointestinal extranodal MZBCL of MALT and of follicular lymphoma.
      PATIENTS AND METHODS: 40 consecutive patients with gastrointestinal extranodal
      MZBCL of MALT (26 men, 14 women, aged 27 - 80 years), and 7 patients with known
      follicular lymphoma of the small intestine (5 men, 2 women, aged 34 - 63 years)
      underwent capsule endoscopy. RESULTS: Involvement of the small intestine was
      identified by capsule endoscopy in all 7 patients with known follicular lymphoma
      of the small intestine. In 6 of 40 patients with gastric extranodal MZBCL of MALT
      abnormal findings could be observed, three of these findings indicative for
      lymphoma involvement of the small intestine. However, in each of these 3 cases,
      intestinal involvement had been already diagnosed by conventional GI endoscopy
      before capsule endoscopy. CONCLUSIONS: Capsule endoscopy is able to detect
      involvement of the small intestine in patients with gastrointestinal lymphoma.
      However, involvement of the small intestine seems to be rare in patients with
      gastric extranodal MZBCL of MALT. In summary, routine diagnostic work-up of the
      small intestine, e. g. by capsule endoscopy seems unnecessary because of the rare
      involvement of the small intestine and an excellent long-term outcome
      irrespective of a possible intestinal manifestation.

PMID- 23955138
TI  - Treatment of metastatic colorectal cancer with cetuximab: influence on the
      quality of life.
AB  - BACKGROUND: Epidermal Growth Factor Receptor (EGFR) antibodies are innovative
      anti-cancer drugs prolonging survival in metastatic colocrectal cancer. However,
      due to adverse drug reactions, patients develop acneform skin toxicities. We
      hypothesized that the skin reaction leads to a decline in general (QOL) and
      dermatological health related quality of life (HQOL). Furthermore, we aimed at
      evaluating predictors for QOL and HQOL to improve individual adjustment of
      therapy. METHODS: 40 outpatients with metastatic colocrectal cancer were involved
      in this study. According to their KRAS status, patients were allocated to 2
      groups: The CTCX group (n = 20; KRAS wild-type) was treated with the EGFR
      antibody Cetuximab plus chemotherapy, the CT group (n = 20; KRAS mutation) was
      receiving chemotherapy only. Psychological assessment consisted of questionaires
      to evaluate QOL and HQOL, depression, coping-styles, health beliefs and the
      patient's personality. RESULTS: Between the two groups, no significanct
      difference in QOL was found, QOL remained stable over the course of treatment.
      Yet, the severity of the skin reactions had a significant influence on HQOL.
      Internal health beliefs and high compliance were found to be protective factors,
      while passive coping strategies, depression and the personality trait neuroticism
      were identified as risk factors. DISCUSSION: Interdisciplinary cooperation
      between medical professionals and psycho-oncologists is strongly recommended to
      encourage patients to embark on and to retain EGFR-antibody therapy. If risk
      factors are present, psycho-oncological therapy should focus on the minimization
      of depression and on the development of active coping strategies.

PMID- 23955139
TI  - [Pitfalls in Diagnosis and Therapy for CMV Colitis in a 30-Year-Old HIV-Positive
      Patient].
AB  - We report on a 30-year-old patient who presented with bloody diarrhoea. After
      initially, assuming a previously not diagnosed ulcerative colitis, an
      immunosuppressive therapy was initiated, a week later an HIV infection stage C2
      according to the CDC classification, complicated by CMV viraemia, was diagnosed.
      In this case report the course of treatment with highly active antiretroviral
      therapy (HAART), ganciclovir and prednisolone is reported and discussed on the
      basis of histological, immunohistochemical and microbiological findings. The case
      illustrates the difficulty to distinguish between ulcerative colitis, immune
      reconstitution syndrome, CMV colitis and HIV-associated diarrhoea.

PMID- 23955140
TI  - [Therapy of Buried Bumper Syndrome via NOTES - A Case Report].
AB  - Mucosal overgrowth and migration of the inner bumper into or even through the
      gastric wall (= buried bumper syndrome) is a possible complication of
      percutaneous endoscopic gastrostomy (PEG). In this case report we describe the
      successful endoscopic recovery of an intraabdominally migrated inner bumper as
      well as reestablishment of PEG using NOTES (Natural Orifice Translumenal
      Endoscopic Surgery). This practical application of the NOTES technique via the
      preexisting transgastric approach (PEG) can therefore be a reasonable alternative
      to a surgical-laparoscopic therapy of the severe buried bumper. 

PMID- 23955141
TI  - [Capsule Endoscopy in Patients with Cardiac Pacemakers and Implantable
      Cardioverter Defibrillators - Is the Formal Contraindication still Justified?].
AB  - BACKGROUND AND AIMS: Capsule endoscopy is an established tool for investigation
      of the small intestine. Because of limited clinical experience in patients with
      cardiac devices the US Food and Drug Administration and the manufacturers
      recommend not to use capsule endoscopy in these patients. METHODS: Studies
      investigating possible interference between small bowel capsule endoscopy and
      cardiac pacemakers and implanted cardioverters were analysed. For the review we
      considered studies published in English or German and indexed in PubMed (Medline)
      as well as relevant abstracts and technical data from the manufacturer. RESULTS:
      In vitro and in vivo studies applying real capsules revealed no clinically
      relevant interference with pacemakers and implanted cardioverters. This evidence
      already has had an impact on clinical practice and recommendations of scientific
      societies. On the other hand wireless telemetry can interfere with CE video.
      CONCLUSION: According to present evidence, small bowel capsule endoscopy can be
      used in patients with pacemakers and implanted cardioverters after obtaining
      informed consent concerning the formal existence of contraindication.

PMID- 23955142
TI  - [S3-guideline colorectal cancer version 1.0].

PMID- 23955143
TI  - Temperature enhanced effects of chlorine exposure on the health status of the
      sentinel organism Mytilus galloprovincialis.
AB  - It now is widely recognised that the global temperature is rising, a phenomenon
      which could alter the effects of pollution on wildlife. In order to assess the
      role of temperature and exposure to chlorine due to cooling water discharges, a
      battery of metabolic, oxidative stress and histological parameters were evaluated
      in Mytilus galloprovincialis after 15 and 30 days at 15  degrees C and at two
      increased temperatures (+5 and +10  degrees C). Diverse gill pathologies such as
      haemolymphatic sinus dilatation, an increased number of mucocytes and
      granulocytes as well as a lower number of cilia were observed after 30 days
      exposure at higher temperatures. Protein, amino acid, triglyceride and fatty acid
      levels decreased when the temperature increased, as a consequence of higher
      energetic demand. Similarly, acetylcholinesterase, catalase and glutathione S
      transferase activities showed an inhibition at higher temperatures, although gill
      lipid peroxidation levels remained unaffected. Our results suggest that increased
      temperatures induce deterioration in the health status of the mussels and in
      their defensive capacity against a polluted environment.

PMID- 23955144
TI  - Attitude of medical school students in China towards genetic testing and
      counseling issues in FXS.
AB  - Fragile X syndrome (FXS) is the most common form of inherited intellectual
      disability. However, genetic testing protocols and genetic counseling guidelines
      for FXS are not yet established in mainland China. In the present study, we
      conducted a comprehensive analysis using a self-administered questionnaire among
      students at the Xiangya medical school to investigate their attitude towards
      genetic testing and counseling issues of FXS. We have gained a general
      understanding of the attitudes of medical students towards these FXS issues in
      China. This information is of immense importance to develop appropriate genetic
      tests and to train counselors for FXS. As the medical school students surveyed
      are prospective physicians who will be a part of the Chinese health system, our
      survey was focused on the basic knowledge of FXS, population-based FXS screening,
      confidentiality and reproductive options for mutation carriers. The study
      demonstrated that only less than one third of the participants had heard about
      FXS. 94.6 % of participants were in favor of FXS screening for women in their
      reproductive age who had a genetic history of FXS. Furthermore, only half of the
      participants would inform their families about their genetic status in case of
      positive test results, and more than half of the participants supported natural
      conception and prenatal diagnosis for FXS mutation carriers. Additional findings
      and research implications are also discussed. This survey targeting potential
      doctors provides important information for the development of FXS genetic test
      and counselor training for the Chinese health system. 

PMID- 23955145
TI  - Pt-Ni alloyed nanocrystals with controlled architectures for enhanced methanol
      oxidation.
AB  - Pt-Ni alloy nanocrystals with controlled architectures (multi-arms and flowers)
      have been synthesized via a simple colloid chemistry method. The crystal surfaces
      possess abundant low-coordination defect sites, where the reaction kinetics of
      methanol oxidation can be improved, resulting in the catalysts exhibiting better
      stability and higher resistance to poisoning. 

PMID- 23955146
TI  - Progress in plant protoplast research.
AB  - In this review we focus on recent progress in protoplast regeneration, symmetric
      and asymmetric hybridization and novel technology developments. Regeneration of
      new species and improved culture techniques opened new horizons for practical
      breeding in a number of crops. The importance of protoplast sources and embedding
      systems is discussed. The study of reactive oxygen species effects and DNA
      (de)condensation, along with thorough phytohormone monitoring, are in our opinion
      the most promising research topics in the further strive for rationalization of
      protoplast regeneration. Following, fusion and fragmentation progress is
      summarized. Genomic, transcriptomic and proteomic studies have led to better
      insights in fundamental processes such as cell wall formation, cell development
      and chromosome rearrangements in fusion products, whether or not obtained after
      irradiation. Advanced molecular screening methods of both genome and cytoplasmome
      facilitate efficient screening of both symmetric and asymmetric fusion products.
      We expect that emerging technologies as GISH, high resolution melting and next
      generation sequencing will pay major contributions to our insights of genome
      creation and stabilization, mainly after asymmetric hybridization. Finally, we
      demonstrate agricultural valorization of somatic hybridization through
      enumerating recent introgression of diverse traits in a number of commercial
      crops.

PMID- 23955148
TI  - Utility of physiologically based modeling and preclinical in vitro/in vivo data
      to mitigate positive food effect in a BCS class 2 compound.
AB  - Physiologically based pharmacokinetic (PBPK) modeling has become a useful tool to
      estimate the performance of orally administrated drugs. Here, we described
      multiple in silico/in vitro/in vivo tools to support formulation development
      toward mitigating the positive food effect of NVS123, a weak base with a pH
      dependent and limited solubility. Administered orally with high-fat meal, NVS123
      formulated as dry filled capsules displayed a positive food effects in humans.
      Three alternative formulations were developed and assessed in in vitro and in
      vivo preclinical and/or clinical studies. By integrating preclinical in vitro and
      in vivo data, the PBPK model successfully estimated the magnitude of food effects
      and the predicted values were within +/- 30% of the observed results. A model
      guided parameter sensitivity analysis illustrated that enhanced solubility and
      longer precipitation times under fed condition were the main reason for enhanced
      NVS123's exposure in presence of food. Eventually, exposure after an amorphous
      formulation was found to be not significantly altered because of remarkably
      enhanced intestinal solubility and reduced precipitation. Gastroplus population
      simulations also suggested that the amorphous formulation is promising in
      mitigating a clinically significant food effect. Overall, these efforts supported
      the rationale of clinical investigation of the new formulation, and more
      importantly, highlighted a practical application of PBPK modeling solving issues
      of undesirable food effects in weakly basic compounds based on preclinical in
      vitro/in vivo data.

PMID- 23955147
TI  - Molecular characterization of cold-responsive basic helix-loop-helix
      transcription factors MabHLHs that interact with MaICE1 in banana fruit.
AB  - Basic helix-loop-helix (bHLH) transcription factors (TFs) are ubiquitously
      involved in the response of higher plants to various abiotic stresses. However,
      little is known about bHLH TFs involved in the cold stress response in
      economically important fruits. Here, five novel full-length bHLH genes,
      designated as MabHLH1-MabHLH5, were isolated and characterized from banana fruit.
      Gene expression profiles revealed that MabHLH1/2/4 were induced by cold stress
      and methyl jasmonate (MeJA) treatment. Transient assays in tobacco BY2
      protoplasts showed that MabHLH1/2/4 promoters were activated by cold stress and
      MeJA treatments. Moreover, protein-protein interaction analysis demonstrated that
      MabHLH1/2/4 not only physically interacted with each other to form hetero-dimers
      in the nucleus, but also interacted with an important upstream component of cold
      signaling MaICE1, with different interaction domains at their N-terminus. These
      results indicate that banana fruit cold-responsive MabHLHs may form a big protein
      complex in the nucleus with MaICE1. Taken together, our findings advance our
      understanding of the possible involvement of bHLH TFs in the regulatory network
      of ICE-CBF cold signaling pathway. 

PMID- 23955149
TI  - Importance of wet packability of component particles in pellet formation.
AB  - This work explored the importance of packability of component particles in the
      different wet processing steps of extrusion-spheronization and investigated
      different processing and formulation approaches for enhancing packing of
      component particles during extrusion-spheronization to produce spherical pellets
      with high yield and narrow size distribution. Various cross-linked polyvinyl
      pyrrolidone (XPVP) and lactose grades with different particle sizes were used as
      pelletization aid and filler in 1:3 binary powder blends. Loosely packed
      extrudates obtained from coarse XPVP/lactose blends possessed low cohesive
      strength and produced irregular shaped pellets with low yield whereas tightly
      packed, rigid extrudates obtained from XPVP/fine lactose grades possessed high
      cohesive strength and produced elongated pellets. Adjustment of spheronization
      tip speed to provide sufficient forces generated by the rotating frictional base
      plate for facilitating packing by rearrangement of component particles improved
      pellet quality. Double extrusion, decreasing particle size of the formulation
      component(s), and/or widening particle size distribution of the powder blend are
      approaches applicable to improve cohesiveness of moistened mass by closer packing
      of component particles for production of good quality pellets. 

PMID- 23955150
TI  - Efficient electrostatic self-assembly of one-dimensional CdS-Au nanocomposites
      with enhanced photoactivity, not the surface plasmon resonance effect.
AB  - A series of CdS nanowire-Au nanocomposites (CdS NW-Au NCs) with different weight
      addition ratios of Au nanoparticles (NPs) are successfully synthesized by using a
      simple and efficient electrostatic self-assembly method at room temperature for
      utilizing the natural surface charge properties of the CdS NWs and Au NPs. These
      natural surface charge properties are dependent on the synthesis approaches. The
      probe reactions for photocatalytic selective reduction of nitroaromatic compounds
      in the aqueous phase under visible light irradiation are utilized to evaluate the
      photoactivity of this series of as-prepared CdS NW-Au NCs. The CdS NW-Au NCs
      exhibit significantly enhanced photoactivity as compared to the CdS nanowires
      (CdS NWs). The addition of Au NPs into the CdS NW domain enables efficient
      enhancement of the lifetime and transfer of photogenerated charge carriers from
      CdS NWs under visible light irradiation. However, the addition of excess amounts
      of Au NPs not only influences the penetration of light but the Au NPs also become
      the recombination centers, and result in decreased photoactivity. The optimal
      proportion of the Au NPs is proved to be 1 wt%, which indicates the synergistic
      effect between the CdS NWs and Au NPs. In addition, the surface plasmon resonance
      (SPR) effect of Au NPs is proved to not play an efficient role in the reaction
      and the possible photocatalytic reaction mechanism is proposed. It is hoped that
      this work could aid in the fabrication of 1-D semiconductor-metal nanocomposites
      by using such a simple and efficient electrostatic self-assembly strategy. In
      addition, it is also expected to enrich and supplement their application as
      visible light photocatalysts toward selective organic transformations through our
      investigation. 

PMID- 23955151
TI  - Cross-neutralization of four paramyxoviruses by a human monoclonal antibody.
AB  - Broadly neutralizing antibodies reactive against most and even all variants of
      the same viral species have been described for influenza and HIV-1 (ref. 1).
      However, whether a neutralizing antibody could have the breadth of range to
      target different viral species was unknown. Human respiratory syncytial virus
      (HRSV) and human metapneumovirus (HMPV) are common pathogens that cause severe
      disease in premature newborns, hospitalized children and immune-compromised
      patients, and play a role in asthma exacerbations. Although antisera generated
      against either HRSV or HMPV are not cross-neutralizing, we speculated that,
      because of the repeated exposure to these viruses, cross-neutralizing antibodies
      may be selected in some individuals. Here we describe a human monoclonal antibody
      (MPE8) that potently cross-neutralizes HRSV and HMPV as well as two animal
      paramyxoviruses: bovine RSV (BRSV) and pneumonia virus of mice (PVM). In its
      germline configuration, MPE8 is HRSV-specific and its breadth is achieved by
      somatic mutations in the light chain variable region. MPE8 did not result in the
      selection of viral escape mutants that evaded antibody targeting and showed
      potent prophylactic efficacy in animal models of HRSV and HMPV infection, as well
      as prophylactic and therapeutic efficacy in the more relevant model of lethal PVM
      infection. The core epitope of MPE8 was mapped on two highly conserved anti
      parallel beta-strands on the pre-fusion viral F protein, which are rearranged in
      the post-fusion F protein conformation. Twenty-six out of the thirty HRSV
      specific neutralizing antibodies isolated were also found to be specific for the
      pre-fusion F protein. Taken together, these results indicate that MPE8 might be
      used for the prophylaxis and therapy of severe HRSV and HMPV infections and
      identify the pre-fusion F protein as a candidate HRSV vaccine. 

PMID- 23955152
TI  - Bacterial colonization factors control specificity and stability of the gut
      microbiota.
AB  - Mammals harbour a complex gut microbiome, comprising bacteria that confer
      immunological, metabolic and neurological benefits. Despite advances in sequence
      based microbial profiling and myriad studies defining microbiome composition
      during health and disease, little is known about the molecular processes used by
      symbiotic bacteria to stably colonize the gastrointestinal tract. We sought to
      define how mammals assemble and maintain the Bacteroides, one of the most
      numerically prominent genera of the human microbiome. Here we find that, whereas
      the gut normally contains hundreds of bacterial species, germ-free mice mono
      associated with a single Bacteroides species are resistant to colonization by the
      same, but not different, species. To identify bacterial mechanisms for species
      specific saturable colonization, we devised an in vivo genetic screen and
      discovered a unique class of polysaccharide utilization loci that is conserved
      among intestinal Bacteroides. We named this genetic locus the commensal
      colonization factors (ccf). Deletion of the ccf genes in the model symbiont,
      Bacteroides fragilis, results in colonization defects in mice and reduced
      horizontal transmission. The ccf genes of B. fragilis are upregulated during gut
      colonization, preferentially at the colonic surface. When we visualize microbial
      biogeography within the colon, B. fragilis penetrates the colonic mucus and
      resides deep within crypt channels, whereas ccf mutants are defective in crypt
      association. Notably, the CCF system is required for B. fragilis colonization
      following microbiome disruption with Citrobacter rodentium infection or
      antibiotic treatment, suggesting that the niche within colonic crypts represents
      a reservoir for bacteria to maintain long-term colonization. These findings
      reveal that intestinal Bacteroides have evolved species-specific physical
      interactions with the host that mediate stable and resilient gut colonization,
      and the CCF system represents a novel molecular mechanism for symbiosis. 

PMID- 23955153
TI  - Pathogen blocks host death receptor signalling by arginine GlcNAcylation of death
      domains.
AB  - The tumour necrosis factor (TNF) family is crucial for immune homeostasis, cell
      death and inflammation. These cytokines are recognized by members of the TNF
      receptor (TNFR) family of death receptors, including TNFR1 and TNFR2, and FAS and
      TNF-related apoptosis-inducing ligand (TRAIL) receptors. Death receptor
      signalling requires death-domain-mediated homotypic/heterotypic interactions
      between the receptor and its downstream adaptors, including TNFR1-associated
      death domain protein (TRADD) and FAS-associated death domain protein (FADD). Here
      we discover that death domains in several proteins, including TRADD, FADD, RIPK1
      and TNFR1, were directly inactivated by NleB, an enteropathogenic Escherichia
      coli (EPEC) type III secretion system effector known to inhibit host nuclear
      factor-kappaB (NF-kappaB) signalling. NleB contained an unprecedented N
      acetylglucosamine (GlcNAc) transferase activity that specifically modified a
      conserved arginine in these death domains (Arg 235 in the TRADD death domain).
      NleB GlcNAcylation (the addition of GlcNAc onto a protein side chain) of death
      domains blocked homotypic/heterotypic death domain interactions and assembly of
      the oligomeric TNFR1 complex, thereby disrupting TNF signalling in EPEC-infected
      cells, including NF-kappaB signalling, apoptosis and necroptosis. Type-III
      delivered NleB also blocked FAS ligand and TRAIL-induced cell death by preventing
      formation of a FADD-mediated death-inducing signalling complex (DISC). The
      arginine GlcNAc transferase activity of NleB was required for bacterial
      colonization in the mouse model of EPEC infection. The mechanism of action of
      NleB represents a new model by which bacteria counteract host defences, and also
      a previously unappreciated post-translational modification. 

PMID- 23955155
TI  - The 2nd edition of consensus statements for the diagnosis and management of
      intestinal Behcet's disease: indication of anti-TNFalpha monoclonal antibodies.
AB  - BACKGROUND: Clinical evidence regarding intestinal Behcet's disease (BD)
      management is lacking and intestinal lesions are a poor prognostic factor. In
      2007, the Japan consensus statement for diagnosis and management of intestinal BD
      was developed. Recently, the efficacy of anti-tumor necrosis factor (TNF)alpha
      monoclonal antibodies (mAbs), and infliximab (IFX) was reported and adalimumab
      (ADA) was approved for intestinal BD in Japan. This study renewed consensus-based
      practice guidelines for diagnosis and treatment of intestinal BD focusing on the
      indication of anti-TNFalpha mAbs. METHODS: An expert panel of Japanese
      gastroenterology and rheumatology specialists was involved. Clinical statements
      for ratings were extracted from the literature, a professional group survey, and
      by an expert panel discussion, which rated clinical statements on a nine-point
      scale. After the first round of ratings, a panelist meeting discussed areas of
      disagreement and clarified areas of uncertainty. The list of clinical statements
      was revised after the panelist meeting and a second round of ratings was
      conducted. RESULTS: Fifteen relevant articles were selected. Based on the first
      edition consensus statement, improved clinical statements regarding indications
      for anti-TNFalpha mAbs use were developed. After a two-round modified Delphi
      approach, the second edition of consensus statements was finalized. CONCLUSIONS:
      In addition to standard therapies in the first edition, anti-TNFalpha mAbs (ADA
      and IFX) should be considered as a standard therapy for intestinal BD.
      Colchicines, thalidomide, other pharmacological therapy, endoscopic therapy, and
      leukocytapheresis were deemed experimental therapies.

PMID- 23955154
TI  - Trends in the susceptibility of methicillin-resistant Staphylococcus aureus to
      nine antimicrobial agents, including ceftobiprole, nemonoxacin, and tyrothricin:
      results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006
      2010.
AB  - This study investigated the in vitro susceptibilities of methicillin-resistant
      Staphylococcus aureus (MRSA) to nine antimicrobial agents in Taiwan. A total of
      1,725 isolates were obtained from 20 hospitals throughout Taiwan from 2006 to
      2010. The minimum inhibitory concentrations (MICs) of the nine agents were
      determined by the agar dilution method. The MICs of mupirocin and tyrothricin
      were determined for 223 MRSA isolates collected from 2009 to 2010. For
      vancomycin, 99.7 % were susceptible; however, 30.0 % (n = 517) exhibited MICs of
      2 MUg/ml and 0.3 % (n = 6) demonstrated intermediate susceptibility (MICs of 4
      MUg/ml). Nearly all isolates (>= 99.9 %) were susceptible to teicoplanin,
      linezolid, and daptomycin. The MIC90 values were 2 MUg/ml for ceftobiprole and 1
      MUg/ml for nemonoxacin. The MIC90 values of mupirocin and tyrothricin were 0.12
      and 4 MUg/ml, respectively. MIC creep was noted for daptomycin during this
      period, but not for vancomycin, teicoplanin, linezolid, or tigecycline. For
      isolates with vancomycin MICs of 2 MUg/ml, the MIC90 values were 2 MUg/ml for
      teicoplanin, 0.5 MUg/ml for daptomycin, and 0.5 MUg/ml for tigecycline. Those
      values were four- to eight-fold higher than those among isolates with vancomycin
      MICs of 0.5 MUg/ml (2, 0.06, and 0.12 MUg/ml, respectively). Of the nine MRSA
      isolates exhibiting non-susceptibility to vancomycin (n = 6), teicoplanin (n =
      1), daptomycin (n = 2), or tigecycline (n = 1), all had different pulsotypes,
      indicating the absence of intra-hospital or inter-hospital spread. The presence
      of a high proportion of MRSA isolates with elevated MICs (2 MUg/ml) and MIC creep
      of daptomycin might alert clinicians on the therapy for serious MRSA infections
      in Taiwan.

PMID- 23955156
TI  - Multispectral imaging with vertical silicon nanowires.
AB  - Multispectral imaging is a powerful tool that extends the capabilities of the
      human eye. However, multispectral imaging systems generally are expensive and
      bulky, and multiple exposures are needed. Here, we report the demonstration of a
      compact multispectral imaging system that uses vertical silicon nanowires to
      realize a filter array. Multiple filter functions covering visible to near
      infrared (NIR) wavelengths are simultaneously defined in a single lithography
      step using a single material (silicon). Nanowires are then etched and embedded
      into polydimethylsiloxane (PDMS), thereby realizing a device with eight filter
      functions. By attaching it to a monochrome silicon image sensor, we successfully
      realize an all-silicon multispectral imaging system. We demonstrate visible and
      NIR imaging. We show that the latter is highly sensitive to vegetation and
      furthermore enables imaging through objects opaque to the eye. 

PMID- 23955157
TI  - Enzyme replacement in neuronal storage disorders in the pediatric population.
AB  - OPINION STATEMENT: In the past 15 years, for select lysosomal storage diseases,
      there has been a shift from symptom management to disease modification in terms
      of treatment strategy, mainly related to use of enzyme replacement therapy (ERT).
      Yet the application of ERT is for very few diseases, and while beneficial, ERT
      does not represent a cure. For some disorders, the advent of ERT has made a
      dramatic impact, while for others, benefits have been much more modest.
      Understanding of the long-term effects as well as the appropriate time for
      initiation of ERT is under exploration in a number of diseases, while the
      feasibility of ERT is still being established for others. No definite effects of
      ERT on central nervous system manifestations of lysosomal storage diseases have
      been observed for any disease to date. New strategies, including intrathecal
      enzyme replacement, gene therapy and substrate reduction therapy are being
      developed in animal models and clinical trials, which hopefully will begin a new
      era of nervous system disease modification in neuronal storage disorders.

PMID- 23955158
TI  - Spatial distribution of polychlorinated dibenzo-p-dioxins and dibenzo-furans
      (PCDDs/Fs) in dust, soil, sediment and health risk assessment from an intensive
      electronic waste recycling site in Southern China.
AB  - Workshop dust, soil and sediment samples were collected to investigate the level
      and spatial distribution of PCDDs/Fs at an intensive electronic waste (e-waste)
      recycling site in Southern China, and also to characterize the dioxin emission in
      different e-waste recycling procedures. The concentrations of total PCDDs/Fs
      ranged from 1866 to 234292 ng kg(-1) for the dust samples, from 3187 to 63998 ng
      kg(-1) dry wt for the top soils, and 33718 ng kg(-1) for the surface sediment.
      All the samples were characterized by abnormally high concentrations of OCDD and
      an extremely low portion of PCDFs. Different e-waste recycling procedures may
      generate different congener profiles. Open burning and dismantling were the two
      procedures emitting relatively higher concentrations of PCDDs/Fs in this case,
      indicating that low-tech recycling operations were one of the major contributors
      of PCDDs/Fs to the environment. The variation and distinction of the
      concentrations and homologue/congener profiles among different environmental
      matrices reveal the characteristics of contaminant environmental behavior and
      fate during the transportation from "source" to "sink". Daily intake of PCDDs/Fs
      through soil ingestion and dermal absorption was negligible, but the rough
      estimated total PCDD/F intake dose far exceeded the tolerance daily intake value
      of 4 pg-TEQ per kg per day recommended by WHO, indicating that residents in
      Longtang were at a high risk of exposure to dioxins, especially children.

PMID- 23955159
TI  - Tooth loss in aggressive periodontitis: a systematic review.
AB  - Aggressive periodontitis (AgP) is thought to have a faster rate of progression
      than chronic periodontitis (CP). However, there is a lack of studies
      systematically investigating disease progression and tooth loss in AgP. A
      systematic search of the literature was conducted by two independent reviewers
      for longitudinal studies including patients with AgP (previously known as
      'periodontosis', 'juvenile' or 'early-onset' periodontitis) indicating measures
      of disease progression. Ovid MEDLINE((r)) and Embase databases were searched for
      at least 5-year longitudinal human studies in AgP patients. In total, 16 studies
      were included in the review, from an initial search of 1,601 titles.
      Heterogeneity was detected for disease definition and clinical data reporting;
      hence meta-analysis was feasible only for the objective measure 'tooth loss'. The
      average tooth loss for all AgP cases was 0.09 (95% C.I. = 0.06-0.16) per patient
      year. The corresponding values by diagnosis were 0.05, 0.14, and 0.12 tooth loss
      per patient-year, respectively, for LAgP, GAgP, and un-specified AgP. For studies
      reporting tooth loss during the 'observational period' (excluding extractions at
      initial therapy), the average tooth loss for AgP was 0.09 per patient-year. High
      heterogeneity was detected for these analyses. In conclusion, most studies report
      good long-term stability of treated AgP cases. 

PMID- 23955160
TI  - Cellular and molecular mechanisms of dental nociception.
AB  - Due, in part, to the unique structure of the tooth, dental pain is initiated via
      distinct mechanisms. Here we review recent advances in our understanding of
      inflammatory tooth pain and discuss 3 hypotheses proposed to explain dentinal
      hypersensitivity: The first hypothesis, supported by functional expression of
      temperature-sensitive transient receptor potential channels, emphasizes the
      direct transduction of noxious temperatures by dental primary afferent neurons.
      The second hypothesis, known as hydrodynamic theory, attributes dental pain to
      fluid movement within dentinal tubules, and we discuss several candidate cellular
      mechanical transducers for the detection of fluid movement. The third hypothesis
      focuses on the potential sensory function of odontoblasts in the detection of
      thermal or mechanical stimuli, and we discuss the accumulating evidence that
      supports their excitability. We also briefly update on a novel strategy for local
      nociceptive anesthesia via nociceptive transducer molecules in dental primary
      afferents with the potential to specifically silence pain fibers during dental
      treatment. Further understanding of the molecular mechanisms of dental pain would
      greatly enhance the development of therapeutics that target dental pain. 

PMID- 23955161
TI  - Autophagy researchers.

PMID- 23955162
TI  - [Dislocation of the atlantoaxial joint].
AB  - Injuries of the cervical spine in adolescents only occur in 0.2 % of cases. Due
      to the mismatch of size of the head in comparison to the relatively weakly
      developed neck muscles at this age, the cranial section is more vulnerable to
      injuries of any kind compared to the lower sections of the cervical spine. In
      children isolated ligament trauma is more common than fractures due to the
      relatively good bone structure combined with a lower bone density but the risk
      for fractures increases with the age of the patient. Atlantoaxial dislocation
      (AAD) in children is a very rare mostly ligamentous injury. A differentiation is
      made between traumatic AAD and the much more common non-traumatic AAD described
      in the literature. Although the cause is still unknown different risk factors
      have been isolated that seem to increase the risk for non-traumatic AAD. The
      following article presents guidelines for the diagnosis and treatment of this
      rare type of injury and also describes the case of a 19-year-old female who
      presented at the emergency department with an AAD without a history of trauma.
      After successful closed repositioning the neck was stabilized in a semi-rigid
      cervical collar for 6 weeks.

PMID- 23955163
TI  - [Proximal femoral fractures in the German external quality assurance module 17/1:
      reasons for delay in surgery].
AB  - BACKGROUND: For the quality indicator "preoperative stay" a part of the external
      quality assurance for proximal femoral fractures (module 17/1), a tolerance range
      for surgery within 48 h after admission of <= 15 % is given. MATERIALS AND
      METHODS: Over a period of 5 years all cases were analyzed with respect to reasons
      for delayed surgery of more than 48 h after admission. RESULTS: A total of 165
      patients (16%) out of 1,036 documented cases had surgery later than 48 h after
      admission. Reasons were pathological bleeding, preoperative poor general
      condition, lack of informed consent, intake of metformin and lacking initial
      radiological detection of fractures. Due to a lack of software-related
      specifications in ten patients a wrong preoperative length of stay was generated.
      CONCLUSION: The significance of the quality indicator "preoperative stay" without
      division into whether this was administrative or patient-related must be
      considered critically. For fall-related fractures in hospital the time of the
      accident or diagnosis should be considered.

PMID- 23955164
TI  - [Nailing of metaphyseal fractures].
AB  - Nailing of metaphyseal fractures demands thorough preoperative planning. The
      trauma surgeon has to take the specific morphology of the fracture, the
      individual anatomy of the broken bone, and the design and characteristics of the
      selected implant into consideration. The fracture has to be precisely reduced and
      the reduction controlled during nail insertion. The reduction technique and
      reduction aids must be chosen preoperatively. The nail has to be introduced with
      care and brought to its correct and ideal position. Only after successful
      proximal and distal interlocking can the nail become the central weight bearing
      implant, which holds the fracture stable and reduced. In the following
      contribution, the specific problems of reduction and nail fixation of metaphyseal
      fractures of the proximal humerus, proximal and distal femur, and proximal and
      distal tibia together with the needed reduction and fixation aids are presented. 

PMID- 23955165
TI  - Comparison of the dissolution rate of ceftriaxone sodium preparations for
      injection.
AB  - This study aimed to compare the dissolution rate of eight different formulations
      of ceftriaxone sodium preparation for injection, the original product and seven
      generic versions. The dissolution time was measured precisely as the point at
      which the freeze-dried ceftriaxone sodium preparation became a transparent
      solution on the addition of 0.9% sodium chloride solution. To investigate whether
      differences in the crystalline structure may explain the differences in
      dissolution rates, the eight products were subjected to X-ray diffraction (XRD)
      and differential scanning calorimetry (DSC). Powder surface characteristics were
      examined, including surface area, amount of water adsorbed, water interactions
      and morphology. The measurement of near-infrared spectroscopy of powder
      preparations was conducted, and we predicted dissolution time by partial least
      squares (PLS). The dissolution time of the eight products were different. There
      were no differences in XRD and DSC findings between the original and generic
      products, surface characteristics, i.e., surface area, morphology etc., were
      different between preparations. On near-infrared (NIR) spectroscopy, a good
      relationship was demonstrated between the actual and predicted dissolution time
      for each ceftriaxone preparation. The difference in dissolution time between the
      eight products was due to differences in powder surface characteristics, such as
      water interaction and crystal shape. Finally, it was shown that the dissolution
      rates of the products could be predicted by NIR analysis. 

PMID- 23955167
TI  - Soil-extractable phosphorus and phosphorus saturation threshold in beef cattle
      pastures as affected by grazing management and forage type.
AB  - Grazing can accelerate and alter the timing of nutrient transfer, and could
      increase the amount of extractable phosphorus (P) cycle from soils to plants. The
      effects of grazing management and/or forage type that control P cycling and
      distribution in pasture's resources have not been sufficiently evaluated. Our
      ability to estimate the levels and changes of soil-extractable P and other crop
      nutrients in subtropical beef cattle pastures has the potential to improve our
      understanding of P dynamics and nutrient cycling at the landscape level. To date,
      very little attention has been paid to evaluating transfers of extractable P in
      pasture with varying grazing management and different forage type. Whether or not
      P losses from grazed pastures are significantly greater than background losses
      and how these losses are affected by soil, forage management, or stocking density
      are not well understood. The objective of this study was to evaluate the effect
      of grazing management (rotational versus "zero" grazing) and forage types (FT;
      bahiagrass, Paspalum notatum, Flugge versus rhizoma peanuts, Arachis glabrata,
      Benth) on the levels of extractable soil P and degree of P saturation in beef
      cattle pastures. This study (2004-2007) was conducted at the Subtropical
      Agricultural Research Station, US Department of Agriculture-Agricultural Research
      Service located 7 miles north of Brooksville, FL. Soil (Candler fine sand) at
      this location was described as well-drained hyperthermic uncoated Typic
      Quartzipsamments. A split plot arrangement in a completely randomized block
      design was used and each treatment was replicated four times. The main plot was
      represented by grazing management (grazing vs. no grazing) while forage types
      (bahiagrass vs. perennial peanut) as the sub-plot treatment. Eight steel
      exclosures (10 * 10 m) were used in the study. Four exclosures were placed and
      established in four pastures with bahiagrass and four exclosures were established
      in four pastures with rhizoma peanuts to represent the "zero" grazing treatment.
      The levels of soil-extractable P and degree of P saturation (averaged across FT
      and soil depth) of 22.1 mg kg(-1) and 11.6 % in pastures with zero grazing were
      not significantly (p <= 0.05) different from the levels of soil-extractable P and
      degree of P saturation of 22.8 mg kg(-1) and 12.9 % in pastures with rotational
      grazing, respectively. On the effect of FT, levels of soil-extractable P and
      degree of P saturation were significantly higher in pastures with rhizoma peanuts
      than in pastures with bahiagrass. There was no net gain of soil-extractable P due
      to the presence of animals in pastures with rotational grazing. Averaged across
      years, soil-extractable P in pastures with rotational grazing and with "zero"
      grazing was less than 150 mg kg(-1), the water quality protection. There had been
      no movement of soil-extractable P into the soil pedon since average degree of P
      saturation in the upper 15 cm was 14.3 % while the average degree of P saturation
      in soils at 15-30 cm was about 9.9 %. Overall, average extractable P did not
      exceed the crop requirement threshold of 50 mg P kg(-1) and the soil P saturation
      threshold of 25 %, suggesting that reactive P is not a problem. Our study
      revealed that rhizoma peanuts and bahiagrass differ both in their capacity to
      acquire nutrients from the soil and in the amount of nutrients they need per unit
      growth. Rhizoma peanuts, which are leguminous forage, would require higher
      amounts of P compared with bahiagrass. The difference in the amount of P needed
      by these forages could have a profound effect on their P uptake that can be
      translated to the remaining amount of P in the soils. Periodic applications of
      additional P may be necessary especially for pastures with rhizoma peanuts to
      sustain their agronomic needs and to potentially offset the export of P due to
      animal production. Addition of organic amendments could represent an important
      strategy to protect pasture lands from excessive soil resources exploitation.

PMID- 23955166
TI  - New insights into Shiga toxin-mediated endothelial dysfunction in hemolytic
      uremic syndrome.
AB  - Shiga toxin-producing E. coli represents a significant global health concern,
      especially as hypervirulent pathogens surface amidst outbreaks of hemolytic
      uremic syndrome (HUS). Shiga toxin (Stx) is key in the microangiopathic events
      underlying the disease and its central role is underscored by the unprecedented
      HUS outbreak in Germany in 2011. The mechanisms of Stx-mediated endothelial
      dysfunction have been a major focus of research that has contributed to the
      current understanding of the pathogenic changes in endothelial phenotype leading
      to HUS. Among the newer concepts are Stx-mediated gene regulation in the absence
      of protein synthesis inhibition, a potential role for complement activation, and
      accumulating evidence for detectable serum markers before the onset of the
      classic clinical features of HUS. Further investigation of newer therapeutic
      targets and potential prognostic markers is essential to assess their utility in
      mitigating disease and/or predicting outcomes and will provide an improved
      overall understanding of HUS pathogenesis. 

PMID- 23955168
TI  - Food consumption and nutritional labeling among immigrants to Israel from the
      former Soviet Union.
AB  - Nutritional labeling helps consumers make healthier choices regarding food
      product purchases. In this study, we examined the difference between immigrants
      from the former Soviet Union who emigrated to Israel beginning in 1990 (IIFSU)
      and the general population of Israel regarding food consumption broadly and the
      use of nutritional labeling specifically. A representative sample of each
      population (n = 592) was composed and interviewed. According to the findings,
      compared to the general population, the IIFSU attribute less importance to health
      factors in purchasing food products and information about the ingredients
      contained in food products; they tend not to follow nutritional labels; and
      report less on the need for nutritional integrative labeling. Following from
      this, in the second part of the study, we investigated which of the socio
      economic variables is most dominant in shaping attitudes towards food consumption
      and nutritional labeling. Only immigration and age were found in correlation with
      attitudes related to healthy food consumption. In contrast, gender, education and
      religious observance did not affect food selection. Immigration was recognized as
      the main factor with more clout than the other variables. In conclusion, it is
      crucial to clarify immigrants' perceptions of the concept of "health" and "proper
      nutrition" in formulating health promotion programs.

PMID- 23955169
TI  - Completion of primary care referrals among New York state refugees.
AB  - An important component of the New York State Refugee Health Program's (NYSRHP)
      mission is to ensure refugees with identified medial conditions are referred to
      primary and specialty care. A programmatic evaluation was conducted to assess the
      completion rate for primary care referral appointments made during the initial
      domestic health assessment among refugees in NYS (exclusive of New York City).
      Upon arrival in NYS, refugees may receive a domestic health assessment by one of
      NYSRHP contracted providers. As part of the assessment, referrals for primary and
      specialty care may be assigned. From July 2010 to June 2011, 69 % of NYS-bound
      refugees that received a primary care referral by a NYSRHP contracted provider
      completed their appointment.

PMID- 23955170
TI  - Requirement of the combination of mushroom body gamma lobe and alpha/beta lobes
      for the retrieval of both aversive and appetitive early memories in Drosophila.
AB  - Extensive studies of Drosophila mushroom body in formation and retrieval of
      olfactory memories allow us to delineate the functional logic for memory storage
      and retrieval. Currently, there is a questionable disassociation of circuits for
      memory storage and retrieval during Drosophila olfactory memory processing.
      Formation of the initial aversive olfactory memory involves mushroom body gamma
      lobe, whereas alpha/beta lobes are reported to be necessary for the retrieval of
      such memory. In contrast, formation and retrieval of the short-term appetitive
      olfactory memory appears to involve gamma lobe. With the help of newly identified
      Gal4 lines and of focusing on 3-h memory for both aversive and appetitive
      conditionings, our reexamination of the retrieval of aversive and appetitive
      olfactory memories suggests a new view. Blocking gamma lobe output led to severe
      deficiency of aversive early memory retrieval and partial impairment of
      appetitive early memory retrieval. Interrupting alpha/beta lobe output impaired
      the retrieval of both aversive and appetitive early memories. The contribution of
      the gamma lobe and alpha/beta lobes appeared to be additive for the retrieval of
      appetitive early memory. Thus, these results suggest that the retrieval of
      aversive and appetitive olfactory early memories requires the synaptic outputs
      from both gamma lobe and alpha/beta lobe neurons. This discovery may help us to
      rethink how aversive and appetitive memories are processed from memory formation
      to memory retrieval. 

PMID- 23955171
TI  - Neuronal nitric-oxide synthase deficiency impairs the long-term memory of
      olfactory fear learning and increases odor generalization.
AB  - Experience-induced changes associated with odor learning are mediated by a number
      of signaling molecules, including nitric oxide (NO), which is predominantly
      synthesized by neuronal nitric oxide synthase (nNOS) in the brain. In the current
      study, we investigated the role of nNOS in the acquisition and retention of
      conditioned olfactory fear. Mice lacking nNOS received six training trials, each
      consisting of an odor-CS co-terminating with a foot shock-US. Mice showed reduced
      freezing responses to the trained odor 24 h and 7 d after training, compared to
      wild-type mice. Pretraining systemic injections of the NO donor, molsidomine,
      rescued fear retention in nNOS knockout mice. In wild-type mice, pretraining
      systemic injections of L-NAME, a nonspecific nNOS blocker, disrupted odor-CS fear
      retention in a dose-dependent manner. To evaluate whether NO signaling is
      involved in generalization of fear memories, nNOS knockout mice and wild-type
      mice receiving L-NAME were trained to one odor and tested with a series of
      similar odors. In both cases, we found increased generalization, as measured by
      increased freezing to similar, unpaired odors. Despite the impairment in fear
      memory retention and generalization, neither mice receiving injections of L-NAME
      nor nNOS knockout mice showed any deficits in either novel odor investigation
      time or odor habituation, suggesting intact olfactory perception and short-term
      memory olfactory learning. These results support a necessary role for neuronal NO
      signaling in the normal expression and generalization of olfactory conditioned
      fear. 

PMID- 23955172
TI  - Do different tests of episodic memory produce consistent results in human adults?
AB  - A number of different philosophical, theoretical, and empirical perspectives on
      episodic memory have led to the development of very different tests with which to
      assess it. Although these tests putatively assess the same psychological
      capacity, they have rarely been directly compared. Here, a sample of
      undergraduates was tested on three different putative tests of episodic memory
      (What-Where-When, Unexpected Question/Source Memory, and Free Recall). It was
      predicted that to the extent to which these different tests are assessing the
      same psychological process, performance across the various tests should be
      positively correlated. It was found that not all tests were related and those
      relationships that did exist were not always linear. Instead, two tests showed a
      quadratic relationship, suggesting the contribution of multiple psychological
      processes. It is concluded that not all putative tests of episodic cognition are
      necessarily testing the same thing. 

PMID- 23955173
TI  - Sequence organization and evolutionary dynamics of Brachypodium-specific
      centromere retrotransposons.
AB  - Brachypodium distachyon is a wild annual grass belonging to the Pooideae, more
      closely related to wheat, barley, and forage grasses than rice and maize. As an
      experimental model, the completed genome sequence of B. distachyon provides a
      unique opportunity to study centromere evolution during the speciation of
      grasses. Centromeric satellite sequences have been identified in B. distachyon,
      but little is known about centromeric retrotransposons in this species. In the
      present study, bacterial artificial chromosome (BAC)-fluorescence in situ
      hybridization was conducted in maize, rice, barley, wheat, and rye using B.
      distachyon (Bd) centromere-specific BAC clones. Eight Bd centromeric BAC clones
      gave no detectable fluorescence in situ hybridization (FISH) signals on the
      chromosomes of rice and maize, and three of them also did not yield any FISH
      signals in barley, wheat, and rye. In addition, four of five Triticeae
      centromeric BAC clones did not hybridize to the B. distachyon centromeres,
      implying certain unique features of Brachypodium centromeres. Analysis of
      Brachypodium centromeric BAC sequences identified a long terminal repeat (LTR)
      centromere retrotransposon of B. distachyon (CRBd1). This element was found in
      high copy number accounting for 1.6 % of the B. distachyon genome, and is
      enriched in Brachypodium centromeric regions. CRBd1 accumulated in active
      centromeres, but was lost from inactive ones. The LTR of CRBd1 appears to be
      specific to B. distachyon centromeres. These results reveal different
      evolutionary events of this retrotransposon family across grass species.

PMID- 23955175
TI  - The effect of hepatic or renal impairment on the pharmacokinetics of edivoxetine,
      a selective norepinephrine transporter reuptake inhibitor.
AB  - PURPOSE: To assess the impact of hepatic or renal impairment on the
      pharmacokinetics (PK) of edivoxetine. METHODS: Two separate multi-center, open
      label studies with males and females were conducted. Subjects were categorized
      according to their hepatic function, determined by the Child-Pugh classification,
      or renal function, determined by creatinine clearance using the Cockcroft-Gault
      equation. Subjects received a single dose of 18 mg in the hepatic impairment
      study or 6 mg in the renal impairment study. Noncompartmental PK parameters were
      computed from the edivoxetine plasma concentration-time data. RESULTS: In the
      hepatic study, the geometric least squares mean (GLSM) and 90 % confidence
      interval (CI) of the ratio [impaired : normal] of area under the concentration
      versus time curve from time zero to infinity (AUC0-infinity; h * ng/mL) was 1.24
      (0.93, 1.64) in the mild, 1.60 (1.21, 2.12) in the moderate, and 1.70 (1.28,
      2.24) in the severe group. In the renal impairment study, the GLSM (90 % CI) of
      the ratio [impaired : normal] of AUC0-infinity was 1.13 (0.73, 1.73) in mild,
      1.90 (1.28, 2.82) in moderate, 1.55 (0.94, 2.55) in severe, and 1.03 (0.66, 1.59)
      in ESRD groups. Overall, the GLSM of the ratio [impaired : normal] of Cmax was
      slightly less than or approximately 1 across the hepatic and renal impairment
      groups. Across both studies, there were no clinically significant changes in
      vital signs and laboratory values, the adverse events were mild in severity and
      mostly related to nervous system and gastrointestinal disorder-related events.
      CONCLUSIONS: PK changes in subjects with hepatic or renal impairment were of
      small magnitude and did not appear to impact overall subject tolerability. Daily
      dosing of edivoxetine in a larger population of impaired subjects, including
      those with dual impairment, would aid in establishing edivoxetine tolerability
      and PK in a clinical practice scenario.

PMID- 23955176
TI  - Modelling the possible bioactivity of ellagitannin-derived metabolites. In silico
      tools to evaluate their potential xenoestrogenic behavior.
AB  - Estrogen Receptors (ERs) are ligand-dependent intracellular transcriptional
      factors involved in many diseases. ERs mediate many of the effects of estrogens,
      but also exogenous compounds are able to interfere with ER, disrupting endocrine
      signaling. Among these xenobiotics, compounds present in food and feed make ERs a
      relevant target in the context of dietary modulation of health. In this sense,
      urolithins, gut microbiota derived metabolites of plant polyphenolic
      ellagitannins, may represent good candidates to act as phytoestrogens that are
      able to modulate the activity of ERs. An in silico method to qualitatively
      evaluate the potential xenoestrogenic agonistic behavior of ellagitannin-derived
      metabolites is proposed. The "full-dry" in silico approach involved structure
      based virtual screening (SBVS), docking simulations and re-scoring procedures.
      Results provided valuable insights about the phase II conjugations
      (glucuronidation, sulfation, and methylation, occurring in vivo) affecting the
      estrogenicity of these compounds on alpha- and beta-ER isoforms. Hydroxylation
      patterns also revealed a significant role in the agonistic behavior of urolithin
      derivatives. On the whole, ellagitannin-derived metabolites exerted different
      predicted xenoestrogenic activity depending on chemical structures, and the
      applied in silico approach may represent a successful and easy choice to analyze
      enormous datasets of food-related compounds in order to understand their
      potential biological features. 

PMID- 23955174
TI  - Comparative epidemiology of hospital-acquired adverse drug reactions in adults
      and children and their impact on cost and hospital stay--a systematic review.
AB  - PURPOSE: To study and analyze the comparative impact of hospital-acquired adverse
      drug reactions (ADRs) in adult and pediatric patients in terms of the economic
      implications, (length of) hospital stay, and salient features in relation to the
      incidence rate, severity, morbidity, mortality, and preventability of the ADRs.
      METHODS: A systematic search to identify and retrieve relevant articles/studies
      in the PubMed, Medline, Scopus, MEDPAR, and Cochrane databases and by the Google
      search engine was performed for the study period 2000 to April 2013. In total, 51
      studies were identified on patients hospitalized for ADRs, and these were
      included in the study. The incidence rate of ADRs, their severity, mortality,
      morbidity, preventability, cost, and association with extended hospital stay due
      to ADRs were extracted and scrutinized. RESULTS: Hospital-acquired ADRs are more
      widely studied in adults than in children, and the incidence rate is higher in
      the former. However, a wide variation in the incidence rate worldwide is observed
      in both groups. Irrespective of the ages of patients, ADRs are among the most
      frequent causes of morbidity and mortality. Interestingly, preventable ADRs are
      more frequently observed in patients at the younger and older ends of the age
      spectrum. Hospital-acquired ADRs place an immense economic burden on healthcare
      systems, with the overall cost for a hospitalized patient with an ADR reported to
      be $2,401 per patient, which is equivalent to a 19.86 % additional increase in
      the total cost of care and an increase in average length of hospital stay of 8.25
      %. CONCLUSION: Based on the findings of this review, we suggest that excellent
      assertive measures of pharmacovigilance with the aim to diminish the incidence
      rate of hospital-acquired ADRs and support the development of interventions are
      needed to promote vital facets of drug safety with an overall objective to avert
      potential ADRs.

PMID- 23955177
TI  - 3D stereophotogrammetric analysis of operative effects after broad median
      craniectomy in premature sagittal craniosynostosis.
AB  - INTRODUCTION: There is ongoing discussion on the diagnostic methods, the need of
      surgical treatment, and the surgical strategies for premature craniosynostosis.
      MATERIALS AND METHODS: This study examined the operative procedure of a
      standardized broad median craniectomy, active tilting of the forehead, and
      bitemporal greenstick fracturing in children with premature sagittal
      craniosynostosis. To objectively analyze the direct surgical results, we used a
      3D stereophotogrammetry scanner, as previously described. RESULTS: A 3D analysis
      showed a significant increase in the width, cranial index (CI), head and coronal
      circumferences, intracranial volume, and cranial base width after surgery. Head
      length was the only parameter that demonstrated a significant decrease
      postoperatively. Asymmetry and the 30 degrees  diagonal difference showed no
      significant changes. CONCLUSION: 3D stereophotogrammetry is a reliable and
      valuable tool with no side effects. It demonstrated that the extended surgical
      procedure achieves good postoperative results with a reduced length and increased
      width and, therefore, an improved CI. Additionally, the total intracranial volume
      was significantly increased after surgery.

PMID- 23955178
TI  - Torticollis as a first sign of posterior fossa and cervical spinal cord tumors in
      children.
AB  - BACKGROUND: Torticollis, despite being well-known neurological manifestation, is
      often underestimated as a first symptom of the abnormalities of posterior cranial
      cavity and cervical spinal cord. OBJECTIVES: The purpose of this study is to
      analyze the occurrence of acquired torticollis in children as a herald sign of
      the tumors of the cervical spinal cord or of the posterior fossa. METHODS:
      Clinical records of 54 cases treated for the tumor of the cervical spinal cord or
      posterior fossa (including congenital ones) were retrospectively reviewed. The
      following data were calculated: the occurrence of the torticollis as a first sign
      of tumors, the duration time from the onset of the symptoms to diagnosis, the
      concurrence of other pathological symptoms, and the diminishing of symptoms of
      the torticollis following treatment. RESULTS: In 12/54 (22.2 %) torticollis was
      first sign of central nervous system tumor and in all of them preceded other
      neurological symptoms. The time from the onset of torticollis to establishing
      diagnosis ranged from 2 to 52 weeks (9.6 weeks on average). Eleven of twelve
      patients were treated surgically--in 10 of them, torticollis disappeared in the
      postoperative course. CONCLUSIONS: Torticollis may be a herald sign of the tumor
      of the cervical spinal cord or the posterior fossa. Those pathologies should be
      considered in the differential diagnosis of the torticollis, particularly if
      accompanied by other symptoms of the focal pathology of central nervous system.
      Awareness of this fact may shorten the time to establish the proper diagnosis.
      Torticollis necessitates exclusion of the posterior fossa and spinal cord tumor.

PMID- 23955180
TI  - Diffusion tensor imaging of the superior cerebellar peduncle.

PMID- 23955179
TI  - High-grade lumbosacral spondylolisthesis reduction and fusion in children using
      transsacral rod fixation.
AB  - PURPOSE: There is no consensus on how to treat surgically high-dysplastic
      developmental spondylolisthesis in children and adolescents. Although reducing
      spinal deformity seems mandatory, the issue of surgical reduction versus in situ
      fusion remains controversial. METHODS: The files of 12 consecutive patients
      surgically treated for a grade 3 or 4 spondylolisthesis were reviewed. The
      treatment consisted in L4 to sacrum reduction and fusion by posterior approach.
      The reduction of lumbopelvic imbalance was made intraoperatively using a trans
      sacral rod fixation technique. RESULTS: Mean preoperative L5 anterior slippage
      was 72.3 % (60 to 95 %). The mean preoperative lumbosacral tilt angle was 70.5
      degrees  (43 to 92 degrees ). Mean final lumbosacral tilt angle was 102 degrees 
      (91 to 114 degrees ). Mean final L5 anterior slippage was 19 % (7 to 63 %).
      Neurological complications (radicular L5 or S1 deficits) were noted in five
      patients. At final follow-up L4 to S1 fusion was achieved in all patients. No
      patient had persistent deficit or radicular pain. CONCLUSIONS: The fusion rate in
      our series proved to be optimal. Thanks to the trans-sacral rod fixation,
      lumbosacral kyphosis correction was very good. The intrasacral positioning of the
      screws reduces the risk of implant prominence especially in such pediatric
      patients. We stress the importance to avoid complete slip reduction in such
      patients to minimize stretching on L5 and S1 roots. No additional immobilization
      is needed due to solid posterior instrumentation. Doing such procedure only by
      posterior approach avoids anterior approach-related complications.

PMID- 23955182
TI  - Palladium(0)-catalyzed intramolecular dearomative arylation of pyrroles.
AB  - The palladium(0)-catalyzed dearomative arylation of pyrroles has been
      accomplished to afford the spironaphthalenepyrrole derivatives in good to
      excellent yields. 

PMID- 23955181
TI  - Hematologic malignancies in the Japanese patients with inflammatory bowel
      disease.
AB  - BACKGROUND: Although attention has been focused for over 20 years on the possible
      increased risk for hematologic malignancies (HM) in patients with inflammatory
      bowel diseases (IBD) receiving immune-modulators or anti-TNF-alpha antibodies,
      the association is still controversial. To understand the actual conditions of HM
      in the Japanese patients with IBD, the research committee for IBD supported by
      the Ministry of Health, Welfare and Labor of Japan (IBD-MHWL) conducted a multi
      center retrospective study. METHODS: Questionnaires for the development of HM in
      IBD patients were sent to the 70 facilities participating with IBD-MHWL in the
      first survey, followed by the second survey using a more detailed questionnaire,
      sent to the 27 members with HM patients. RESULTS: Out of a total of 36,939 IBD
      patients in 70 facilities, 28 cases of HM related with IBD [12 of 10,500 UC
      patients (0.11 %), 16 of 6,310 CD patients (0.25 %)] were analyzed. The numbers
      of UC patients who developed HM were 2 (0.15 %) from the group receiving and 10
      (0.13 %) from the group non-receiving thiopurine, without significant
      differences. The numbers of CD patients who developed HM were 4 (0.39 %) from the
      group receiving and 12 (0.21 %) from the group non-receiving thiopurine, without
      significant differences. The odds ratios of developing HM by thiopurine were 1.37
      (95 % CI 0.30-6.24) in UC patients and 1.86 (95 % CI 0.60-5.78) in CD patients.
      CONCLUSIONS: Our results suggested that thiopurine therapy may not be a risk
      factor for HM in Japanese patients with IBD. Further accumulation of cases and
      prospective studies are necessary to conclude this important issue.

PMID- 23955183
TI  - High-flexion mobile-bearing knees: impact on patellofemoral outcomes in 159
      patients.
AB  - Ethnic cultural demands of the patient have encouraged surgeons to use high
      flexion designs. It has been speculated that these high-flexion designs may
      produce higher incidence of patellofemoral complications over conventional
      designs. We wish to report 5- to 7-year follow-up of this design with special
      emphasis on patellofemoral outcomes. We performed a prospective study involving
      159 patients who underwent computer-assisted simultaneous bilateral total knee
      arthroplasty (TKA) with high-flexion design. Patients were evaluated clinically
      using Knee Society score (KSS), Western Ontario and McMaster University
      Osteoarthritis (WOMAC) score, and Hospital for Special Surgery patella score with
      a minimum follow-up period of 5 years. At last follow-up, mean scores were KSS
      (88.7), WOMAC (48.5), and HSS (86.7). All the scores improved postoperatively.
      Average preoperative range of motion was 108 degrees, which improved to 132
      degrees postoperatively. There was no evidence of loosening or spin out in our
      study. Our study shows that TKA done using high-flexion rotating platform design
      results in near normal patellofemoral tracking patterns with improvement in
      function. The level of evidence of the study is IV. 

PMID- 23955184
TI  - Intraoperative pharmacotherapeutic blood management strategies in total knee
      arthroplasty.
AB  - Bone and soft tissue bleeding often results in substantial amounts of blood loss
      following total knee arthroplasty. Multiple studies have reported that cumulative
      blood loss varies between 500 and 1,500 mL in primary settings. Increased
      perioperative blood loss frequently requires allogeneic blood transfusions to
      improve the hematocrit and the hemoglobin levels. However, allogeneic transfusion
      is associated with risks of immunosuppression, transfusion reactions, graft
      versus host disease, and transmission of infections. To avoid these problems and
      reduce costs of transfusion, multiple intraoperative pharmacotherapeutic
      strategies have been developed. The various pharmacotherapeutic agents currently
      used are tranexamic acid, epsilon-aminocaproic acid, fibrin, thrombin, lavage
      with epinephrine, and norepinephrine. However, the relative efficacy and the cost
      effectiveness of these techniques may vary. Thus, the purpose of this study was
      to provide a brief overview of the relative efficacy of various intraoperative
      pharmacological methods currently in use for decreasing blood loss following
      total knee arthroplasty and describe their potential complications associated
      with their use. 

PMID- 23955185
TI  - Blood management strategies in primary and revision total knee arthroplasty for
      Jehovah's Witness patients.
AB  - Primary or revision total knee arthroplasties (TKAs) may be associated with a
      marked amount of intraoperative or postoperative blood loss that potentially may
      lead to the need for blood transfusions. However, Jehovah's Witnesses usually
      refuse blood transfusions because of their religious beliefs. This may create
      clinical or ethical challenges for the treating physicians. Therefore, following
      established blood management protocols specifically designed for these patients
      may be beneficial for the performance of safe and transfusion-free procedures
      with minimal complications. In this report, we provide an overview of various
      potential preoperative, intraoperative, and postoperative blood management
      measures that may be used for the care of Jehovah's Witnesses who undergo knee
      arthroplasty procedures. In addition, we review reported outcomes of primary and
      revision TKAs in these patients. 

PMID- 23955186
TI  - Quadriceps and patellar tendon ruptures.
AB  - The diagnosis of quadriceps and patellar tendon ruptures requires a high index of
      suspicion and thorough history-taking to assess for medical comorbidities that
      may predispose patients to tendon degeneration. Radiographic assessment with
      plain films supplemented by ultrasound and magnetic resonance imaging when the
      work-up is equivocal further aids diagnosis; however, advanced imaging is often
      unnecessary in patients with functional extensor mechanism deficits. Acute repair
      is preferred, and transpatellar bone tunnels serve as the primary form of
      fixation when the tendon rupture occurs at the patellar insertion, with or
      without augmentation depending on surgeon preference. Chronic tears and
      disruptions following total knee arthroplasty are special cases requiring
      reconstructions with allograft, synthetic mesh, or autograft. Rehabilitation
      protocols generally allow immediate weight-bearing with the knee locked in
      extension and crutch support. Limited arc motion is started early with active
      flexion and passive extension and then advanced progressively, followed by full
      active range of motion and strengthening. Complications are few but include
      quadriceps atrophy, knee stiffness, and rerupture. Outcomes are excellent if
      repair is done acutely, with poorer outcomes associated with delayed repair. 

PMID- 23955187
TI  - Complications of patellar fracture repair: treatment and results.
AB  - Open reduction and internal fixation (ORIF) of patellar fractures generally leads
      to good results; however, the potential for surgical complications exists.
      Nonunion, infection, posttraumatic arthritis, arthrofibrosis, symptomatic
      hardware, and extensor mechanism insufficiency have all been described following
      patellar ORIF, and the risk of their occurrence may be augmented by patient-,
      injury-, and treatment-related factors. When complications arise, advanced
      reconstructive techniques are often required for successful management. This
      review will report the incidence of the aforementioned complications, highlight
      risk factors contributing to their frequency, discuss treatment options, and
      present the reported results of selected treatment strategies from available
      literature. 

PMID- 23955188
TI  - Substandard and counterfeit medicines: a systematic review of the literature.
AB  - OBJECTIVE: To explore the evidence available of poor-quality (counterfeit and
      substandard) medicines in the literature. DESIGN: Systematic review. DATA
      SOURCES: Databases used were EMBASE, MEDLINE, PubMed and the International
      Pharmaceutical Abstracts, including articles published till January 2013.
      ELIGIBILITY CRITERIA: Prevalence studies containing original data. WHO
      definitions (1992) used for counterfeit and substandard medicines. STUDY
      APPRAISAL AND SYNTHESIS: Two reviewers independently scored study methodology
      against recommendations from the MEDQUARG Checklist. Studies were classified
      according to the World Bank classification of countries by income. DATA
      EXTRACTION: Data extracted: place of study; type of drugs sampled; sample size;
      percentage of substandard/counterfeit medicines; formulations included; origin of
      the drugs; chemical analysis and stated issues of counterfeit/substandard
      medicines. RESULTS: 44 prevalence studies were identified, 15 had good
      methodological quality. They were conducted in 25 different countries; the
      majority were in low-income countries (11) and/or lower middle-income countries
      (10). The median prevalence of substandard/counterfeit medicines was 28.5% (range
      11-48%). Only two studies differentiated between substandard and counterfeit
      medicines. Prevalence data were limited to antimicrobial drugs (all 15 studies).
      13 studies involved antimalarials, 6 antibiotics and 2 other medications. The
      majority of studies (93%) contained samples with inadequate amounts of active
      ingredients. The prevalence of substandard/counterfeit antimicrobials was
      significantly higher when purchased from unlicensed outlets (p<0.000; 95% CI 0.21
      to 0.32). No individual data about the prevalence in upper middle-income
      countries and high-income countries were available. LIMITATIONS: Studies with
      strong methodology were few. The majority did not differentiate between
      substandard and counterfeit medicines. Most studies assessed only a single
      therapeutic class of antimicrobials. CONCLUSIONS: The prevalence of poor-quality
      antimicrobial medicines is widespread throughout Africa and Asia in lower income
      countries and lower middle-income countries . The main problem identified was
      inadequate amounts of the active ingredients.

PMID- 23955189
TI  - Changing associations of episiotomy and anal sphincter injury across risk strata:
      results of a population-based register study in Finland 2004-2011.
AB  - OBJECTIVES: To evaluate the changing association between lateral episiotomy and
      obstetric anal sphincter injury (OASIS) for women with low and high baseline risk
      of OASIS. DESIGN: A population-based register study. SETTING: Data gathered from
      the Finnish Medical Birth Register for the years 2004-2011. PARTICIPANTS: All
      women with spontaneous vaginal or vacuum-assisted singleton births in Finland
      (n=384 638). MAIN OUTCOME MEASURE: OASIS incidence. RESULTS: During the study
      period, the incidence of OASIS increased from 1.3% to 1.7% in women with first
      vaginal births, including women admitted for first vaginal birth after a prior
      caesarean section and from 0.1% to 0.3% in women with at least one prior birth,
      whereas episiotomy rates declined from 56.7% to 45.5% and 10.1- 5.3%,
      respectively. At the study onset, when episiotomy was used more widely, it was
      negatively associated with OASIS in women with first vaginal births, but as
      episiotomy use declined it became positively associated with OASIS. Women with
      episiotomy were complicated by OASIS with clearly higher risk scores than women
      without episiotomy suggesting that episiotomy was clearly protective against
      OASIS. OASIS occurred with lower mean risk scores among women with and without
      episiotomy over time. However, OASIS incidences increased only among women with
      episiotomy, whereas it decreased or remained among women without episiotomy.
      CONCLUSIONS: The cross-over effect between episiotomy and OASIS could be
      explained by increasing disparity in baseline OASIS risk between treated and
      untreated women, since episiotomy use declined most in women at low OASIS risk.
      Episiotomy rate can be safely reduced in low-risk women but interestingly along
      with the policy change the practice to cut the episiotomy became less protective
      among high-risk women.

PMID- 23955190
TI  - To develop and measure the effectiveness and acceptability of a pharmacy-based
      chlamydia screening intervention in Australia.
AB  - OBJECTIVES: To develop and measure the effectiveness and acceptability of a
      pharmacy-based chlamydia screening intervention called Emergency Contraception
      Mediated Pharmacy Access to Chlamydia Testing (ECOMPACT). DESIGN: Selective,
      opportunistic and cross-sectional study targeting asymptomatic women requesting
      emergency contraception (EC). SETTING: 20 community pharmacies in the Perth
      metropolitan region, Australia. METHODS: ECOMAPCT was developed through
      literature review and stakeholder consensus. Pharmacists were trained to offer
      ECOMPACT after the EC consultation. Women with signs and symptoms of sexually
      transmitted infections (STI) were referred to a physician for a full sexual
      health check. Asymptomatic women were offered a free ECOMPACT testing kit. The
      women self-collected a low-vaginal swab and returned their pathological specimen
      to designated drop-off sites. A pathology service analysed the specimens and sent
      the results to a sexual health physician. The effectiveness of ECOMPACT was
      determined by the uptake of the intervention and how well the target population
      was reached. An effective screening rate was calculated. Qualitative analysis was
      undertaken to understand acceptability issues from the perspective of the
      consumer and the pharmacists. RESULTS: Of the 769 EC consultations in a 6-month
      period, 569 (78%) women were given information on chlamydia screening. All 247
      (41%) agreed to participate. 81 (33%) of these women were ineligible. They were
      either symptomatic (n=33; 41%), or were under 18 years of age (n=48; 59%).
      Pharmacists successfully requested 166 (67%) pathology tests, of which 46 (28%)
      were returned to a pathology drop-off site. All tested negative for Chlamydia
      trachomatis. The effective screening rate was 6%. Consumers and pharmacists
      considered ECOMPACT to be highly convenient and the time taken to offer a
      chlamydia test along with an EC consultation as highly appropriate. CONCLUSIONS:
      ECOMPACT was found to be simple, effective and acceptable. Given the opportunity,
      adequate training and support, community pharmacists in Australia were capable of
      requesting direct-to-consumer chlamydia tests.

PMID- 23955191
TI  - Ionic supramolecular bonds preserve mechanical properties and enable synergetic
      performance at high humidity in water-borne, self-assembled nacre-mimetics.
AB  - Although tremendous effort has been focused on enhancing the mechanical
      properties of nacre-mimetic materials, conservation of high stiffness and
      strength against hydration-induced decay of mechanical properties at high
      humidity remains a fundamental challenge in such water-borne high-performance
      materials. Herein, we demonstrate that ionic supramolecular bonds, introduced by
      infiltration of divalent Cu(2+) ions, allow efficient stabilization of the
      mechanical properties of self-assembled water-borne nacre-mimetics based on
      sustainable sodium carboxymethylcellulose (Na(+)CMC) and natural sodium
      montmorillonite nanoclay (Na(+)MTM) against high humidity (95% RH). The
      mechanical properties in the highly hydrated state (Young's modulus up to 13.5
      GPa and tensile strength up to 125 MPa) are in fact comparable to a range of non
      crosslinked nacre-mimetic materials in the dry state. Moreover, the Cu(2+)
      treated nacre-inspired materials display synergetic mechanical properties as
      found in a simultaneous improvement of stiffness, strength and toughness, as
      compared to the pristine material. Significant inelastic deformation takes place
      considering the highly reinforced state. This contrasts the typical behaviour of
      tight, covalent crosslinks and is suggested to originate from a sacrificial,
      dynamic breakage and rebinding of transient supramolecular ionic bonds.
      Considering easy access to a large range of ionic interactions and alteration of
      counter-ion charge via external stimuli, we foresee responsive and adaptive
      mechanical properties in highly reinforced and stiff bio-inspired bulk
      nanocomposites and in other bio-inspired materials, e.g. nanocellulose papers and
      peptide-based materials. 

PMID- 23955193
TI  - Postoperative opioid administration inhibits bone healing in an animal model.
AB  - BACKGROUND: The current mainstay of orthopaedic pain control is opioid analgesics
      but there are few studies in the literature evaluating the effects of opioids on
      bone healing. QUESTIONS/PURPOSES: The purpose of this study was to use a rat
      fracture model to evaluate the effects of opioid administration on osseous union
      in the acute (4 weeks) and subacute (8 weeks) setting in an operatively
      stabilized fracture. We asked the following question: does morphine
      administration alter (1) fracture callus strength; (2) callus volume and
      formation; and (3) morphology and early remodeling to final osseous union?
      METHODS: A 0.4-mm femoral osteotomy gap was created in 50 Sprague-Dawley rats
      using an established model. Postoperatively, rats were randomized to control
      versus morphine-treated study groups. Equal numbers of rats from each group were
      euthanized at 4 weeks and 8 weeks postoperatively. Three-point bend biomechanical
      testing was performed to evaluate postoperative callus strength. Micro-CT scans
      and histological analyses were used to evaluate postoperative callus volume and
      formation, morphology, and features of early remodeling. RESULTS: Biomechanical
      testing identified a statistically significant (p = 0.048) reduction in callus
      strength in morphine-treated animals 8 weeks postoperatively compared with
      controls. Radiographic and histological analysis showed delayed callus maturation
      and lack of remodeling in the morphine group compared with control animals at 8
      weeks. Micro-CT analysis expressed remodeling and resorption as a decrease in
      callus volume over the two time points. The control group had significant levels
      of resorption decreasing 29% (p = 0.023) over the 4-week to 8-week time interval.
      Morphine administration inhibited callus resorption and remodeling with only a
      13% decrease (p = 0.393) in callus volume comparing these time points. The callus
      inhibition associated with morphine administration was not as evident in the
      acute, 4-week time setting. CONCLUSIONS: Morphine administration inhibited callus
      strength in this animal model. This finding is likely consistent with the
      observation that the callus and healing bone appear to have a decreased rate of
      maturation and remodeling seen at 8 weeks. CLINICAL RELEVANCE: This study
      identifies that administration of an opioid pain medication leads to weaker
      callus and impedes callus maturation compared with controls. These findings may
      provide the impetus to alter our current orthopaedic analgesic gold standard
      toward more multimodal and opioid-limiting pain control regimens.

PMID- 23955192
TI  - Challenges in outcome measurement: discrepancies between patient and provider
      definitions of success.
AB  - BACKGROUND: Some orthopaedic procedures, including TKA, enjoy high survivorship
      but leave many patients dissatisfied because of residual pain and functional
      limitations. An important cause of patient dissatisfaction is unfulfilled
      preoperative expectations. This arises, in part, from differences between
      provider and patient in their definition of a successful outcome. WHERE ARE WE
      NOW?: Patients generally are less satisfied with their outcomes than surgeons.
      While patients are initially concerned with symptom relief, their long-term
      expectations include return of symptom-free function, especially in terms of
      activities that are personally important. While surgeons share their patients'
      desire to achieve their goals, they are aware this will not always occur.
      Conversely, patients do not always realize some of their expectations cannot be
      met by current orthopaedic procedures, and this gap in understanding is an
      important source of discrepancies in expectations and patient dissatisfaction.
      WHERE DO WE NEED TO GO?: An essential prerequisite for mutual understanding is
      information that is accurate, objective, and relevant to the patient's condition
      and lifestyle. This critical information must also be understandable within the
      educational and cultural background of each patient to enable informed
      participation in a shared decision making process. Once this is achieved, it will
      become easier to formulate similar expectations regarding the likely level of
      function and symptom relief and the risk of adverse events, including persistent
      pain, complications, and revision surgery. HOW DO WE GET THERE?: Predictive
      models of patient outcomes, based on objective data, are needed to inform
      decision making on the individual level. This can be achieved once comprehensive
      data become available capturing the lifestyles of patients of diverse ages and
      backgrounds, including data documenting the frequency and intensity of
      participation in sporting and recreational activities. There is also a need for
      greater attention to the process of informing patients of the outcome of
      orthopaedic procedures, not simply for gaining more meaningful consent, but so
      that patients and providers may achieve greater alignment of expectations and
      increased acceptance of both the benefits and limitations of alternative
      treatments.

PMID- 23955194
TI  - Tracked ultrasound snapshots in percutaneous pedicle screw placement navigation:
      a feasibility study.
AB  - BACKGROUND: Computerized navigation improves the accuracy of minimally invasive
      pedicle screw placement during spine surgery. Such navigation, however, exposes
      both the patient and the staff to radiation during surgery. To avoid
      intraoperative exposure to radiation, tracked ultrasound snapshots-ultrasound
      image frames coupled with corresponding spatial positions-could be used to map
      preoperatively defined screw plans into the intraoperative coordinate frame. The
      feasibility of such an approach, however, has not yet been investigated.
      QUESTIONS/PURPOSES: Are there vertebral landmarks that can be identified using
      tracked ultrasound snapshots? Can tracked ultrasound snapshots allow preoperative
      pedicle screw plans to be accurately mapped--compared with CT-derived pedicle
      screw plans--into the intraoperative coordinate frame in a simulated setting?
      METHODS: Ultrasound visibility of registration landmarks was checked on
      volunteers and phantoms. An ultrasound machine with integrated electromagnetic
      tracking was used for tracked ultrasound acquisition. Registration was performed
      using 3D Slicer open-source software (www.slicer.org). Two artificial lumbar
      spine phantoms were used to evaluate registration accuracy of pedicle screw plans
      using tracked ultrasound snapshots. Registration accuracy was determined by
      comparing the ultrasound-derived plans with the CT-derived plans. RESULTS: The
      four articular processes proved to be identifiable using tracked ultrasound
      snapshots. Pedicle screw plans were registered to the intraoperative coordinate
      system using landmarks. The registrations were sufficiently accurate in that none
      of the registered screw plans intersected the pedicle walls. Registered screw
      plan positions had an error less than 1.28 +/- 1.37 mm (average +/- SD) in each
      direction and an angle difference less than 1.92 degrees  +/- 1.95 degrees 
      around each axis relative to the CT-derived positions. CONCLUSIONS: Registration
      landmarks could be located using tracked ultrasound snapshots and permitted
      accurate mapping of pedicle screw plans to the intraoperative coordinate frame in
      a simulated setting. CLINICAL RELEVANCE: Tracked ultrasound may allow accurate
      computer-navigated pedicle screw placement while avoiding ionizing radiation in
      the operating room; however, further studies that compare this approach with
      other navigation techniques are needed to confirm the practical use of this new
      approach.

PMID- 23955195
TI  - Elastic nailing for pediatric subtrochanteric and supracondylar femur fractures.
AB  - BACKGROUND: Subtrochanteric and supracondylar femur fractures are difficult
      injuries to treat in children. Although elastic stable intramedullary nails are
      commonly used for pediatric femur shaft fractures, there is little information on
      their effectiveness for managing pediatric subtrochanteric and supracondylar
      femur fractures. QUESTIONS/PURPOSES: We (1) evaluated radiographic union rates
      and fracture alignment after elastic nailing of pediatric subtrochanteric and
      supracondylar femur fractures, (2) identified complications, and (3) determined
      risk factors for complications. METHODS: Between 2005 and 2011, 36
      subtrochanteric fractures and eight supracondylar femur fractures were treated
      with elastic stable intramedullary nails and had complete followup until clinical
      and radiographic union. Elastic nailing was used for subtrochanteric fractures in
      children 5 to 12 years of age or after failed spica cast treatment in younger
      children and for displaced supracondylar fractures in children older than 5
      years. Fracture alignment and union were measured on radiographs, and
      complications were identified from review of patient charts. Patients with and
      without complications were compared using nonparametric tests to identify risk
      factors. RESULTS: All fractures healed; 23 of 33 (70%) subtrochanteric femur
      fractures and five of seven (71%) supracondylar femur fractures healed with
      anterior angulation of about 5 degrees . For subtrochanteric fractures,
      complications included repositioning/removal of nails before radiographic union
      (n = 4), malunion (n = 2), fracture (n = 1), irritation (n = 1) at nail insertion
      site, and limb length discrepancy (n = 1); despite these complications, there
      were 22 (61%) excellent, 12 (33%) satisfactory, and only two (6%) poor outcomes.
      For supracondylar fractures, complications included infection after nail removal
      (n = 1) and nail site irritation (n = 2); there were three (38%) excellent, five
      (62%) satisfactory, and no poor outcomes. Complications were more likely after
      subtrochanteric fracture during motor vehicle accident (p = 0.045). CONCLUSIONS:
      Although complication rates are high with elastic nailing for pediatric
      subtrochanteric (22%) and supracondylar (38%) femur fractures, elastic nailing
      represents an important option for difficult-to-manage femur fractures. LEVEL OF
      EVIDENCE: Level IV, therapeutic study. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 23955196
TI  - Nd:YAG laser in occlusal caries prevention of primary teeth: a randomized
      clinical trial.
AB  - Dental caries is still the most prevalent chronic disease affecting human
      populations. Among the preventive treatments performed, it has been reported that
      laser irradiation combined with topical fluoride can induce an even greater
      increase in enamel caries resistance. The aim of this study was to evaluate the
      Nd:YAG laser, with or without fluoride, in occlusal caries prevention of the
      primary dentition. A double-blind split-mouth study design was used. Fifty-two
      children with high caries risk (7.6 +/- 1.4 years) were selected and received the
      following: G1--the first molar was a negative control, and the second received a
      resin sealant; G2--the first molar was a negative control, and the second
      received laser irradiation (50 mJ, 10 Hz, 0.5 W); G3--the first molar received
      only acidulate phosphate fluoride (APF), and the second received APF + laser; G4-
      fisrt molar received only fluoride varnish, and the second received fluoride
      varnish + laser. Patients were followed up to 12 months to evaluate the presence
      of white-spot lesions and/or caries cavities by three calibrated observers.
      Thirty-five patients completed the study. Significant differences were found
      between the treatment and control groups (p < 0.05). The laser-alone and resin
      sealant resulted in statistically lower caries formation than the negative
      control group (p < 0.05). Nd:YAG laser irradiation in primary teeth effectively
      prevented occlusal caries in pits and fissures when used alone with lower energy
      over a 1-year period.

PMID- 23955197
TI  - Has the world really survived the population bomb? (Commentary on "how the world
      survived the population bomb: lessons from 50 years of extraordinary demographic
      history").
AB  - In his PAA presidential address and corresponding article in Demography, David
      Lam (Demography 48:1231-1262, 2011) documented the extraordinary progress of
      humankind-vis-a-vis poverty alleviation, increased schooling, and reductions in
      mortality and fertility-since 1960 and noted that he expects further improvements
      by 2050. However, although Lam briefly covered the problems of global warming and
      pollution, he did not address several other major environmental problems that are
      closely related to the rapid human population growth in recent decades and to the
      progress he described. This commentary highlights some of these problems to
      provide a more balanced perspective on the situation of the world. Specifically,
      humans currently are using resources at an unsustainable level. Groundwater
      depletion and overuse of river water are major problems on multiple continents.
      Fossil fuel resources and several minerals are being depleted. Other major
      problems include deforestation, with the annual forest clearing globally
      estimated to be an area the size of New York State; and species extinction, with
      rates estimated to be 100 to 1,000 times higher than background rates. Principles
      of ecological economics are presented that allow an integration of ecology and
      economic development and better potential for preservation of the world for
      future generations. 

PMID- 23955198
TI  - Value of FDG-PET/CT examinations in different cancers of children, focusing on
      lymphomas.
AB  - The aim of the study was to assess sensitivity and specificity of FDG-PET/CT in
      different forms of childhood cancer. We retrospectively evaluated the results
      dedicated of 162 FDG-PET/CT examinations of 86 children treated with: Hodgkin
      lymphoma (HL; n = 31), non-Hodgkin lymphoma (NHL; n = 30) and other high grade
      solid tumors (n = 25). Patients were admitted and treated in two departments of
      pediatric hematology and oncology in Hungary. FDG-PET/CT was performed for
      staging (n = 25) and for posttreatment evaluation (n = 137). Imaging was
      performed in three FDG-PET/CT Laboratories, using dedicated PET/CT scanners.
      False positive results were defined as resolution or absence of disease
      progression over at least 1 year on FDG-PET/CT scans without any intervention. In
      some cases histopathological evaluation of suspicious lesions was performed. Fals
      negative results were defined as negative FDG-PET/CT results in case of active
      malignancy. Positive predictive values (PPV) and negative predictive values (NPV)
      were calculated. NPV was 100%. The highest PPV was observed in high grade solid
      tumors (81%), followed by HL (65%) and NHL (61%). There was a major difference of
      PPV in different histological types of HL (50% in HL of mixed-cellularity
      subtype, 90% in nodular sclerosing, and 100% in lymphocyte-rich and lymphocyte
      depleted HL). We treated one patient with nodular lymphocyte predominant HL, who
      had 5 false positive FDG-PET/CT results. PPV of T- and B-lineage NHL were similar
      (60% and 62%, respectively). We observed an interesting difference of PPV in
      different stages of HL and NHL. In HL PPV was higher in early than in advanced
      disease forms: 66% in stage II HL and 60% in stage III HL, whereas there was an
      inverse relationship between PPV and disease stages in NHL 0% in stage I and II
      patients, 67% in stage III and 100% in stage IV patients. PPV was lower in males
      (54%) than in females (65%). PPV were 64% vs. 58% in patients under vs. over 10
      years of age. Negative FDG-PET/CT results during follow-up reliably predict the
      absence of malignancy. Positive FDG-PET/CT scan results in general have a low
      PPV. The relatively high PPV in patients with histologically proven high grade
      solid tumors, advanced stages of NHL and with nodular sclerosing, lymphocyte-rich
      and lymphocyte depleted subtypes of HL warrant a confirmation by biopsy, whereas
      the watch-and-wait approach can be used in other forms of childhood cancer
      patients with a positive FDG-PET/CT result in course of follow-up examinations.

PMID- 23955199
TI  - Halt the avalanche of performance metrics.

PMID- 23955211
TI  - US brain project puts focus on ethics.

PMID- 23955212
TI  - Russia pins hopes on science city.

PMID- 23955213
TI  - Europe sets sights on lasers.

PMID- 23955214
TI  - India spurns cancer patents.

PMID- 23955215
TI  - Evidence-based justice: corrupted memory.

PMID- 23955218
TI  - Q&A: life-cycle imager. Interview by Jascha Hoffman.

PMID- 23955216
TI  - Ecosystems: climate change must not blow conservation off course.

PMID- 23955220
TI  - Careers: Ireland's research output set to slide.

PMID- 23955221
TI  - Environment: curb clearance for oil-palm plantations.

PMID- 23955222
TI  - Reproductive therapy: HFEA responds on germline therapy.

PMID- 23955223
TI  - Technology: new electricity grids must develop in sync.

PMID- 23955224
TI  - Wildlife protection: seize diplomats smuggling ivory.

PMID- 23955225
TI  - Materials science: composite for smarter windows.

PMID- 23955226
TI  - Gene therapy: primed for take-off.

PMID- 23955227
TI  - Quantum communication: reliable teleportation.

PMID- 23955228
TI  - Climate extremes and the carbon cycle.
AB  - The terrestrial biosphere is a key component of the global carbon cycle and its
      carbon balance is strongly influenced by climate. Continuing environmental
      changes are thought to increase global terrestrial carbon uptake. But evidence is
      mounting that climate extremes such as droughts or storms can lead to a decrease
      in regional ecosystem carbon stocks and therefore have the potential to negate an
      expected increase in terrestrial carbon uptake. Here we explore the mechanisms
      and impacts of climate extremes on the terrestrial carbon cycle, and propose a
      pathway to improve our understanding of present and future impacts of climate
      extremes on the terrestrial carbon budget. 

PMID- 23955229
TI  - A variable absorption feature in the X-ray spectrum of a magnetar.
AB  - Soft-gamma-ray repeaters (SGRs) and anomalous X-ray pulsars (AXPs) are slowly
      rotating, isolated neutron stars that sporadically undergo episodes of long-term
      flux enhancement (outbursts) generally accompanied by the emission of short
      bursts of hard X-rays. This behaviour can be understood in the magnetar model,
      according to which these sources are mainly powered by their own magnetic energy.
      This is supported by the fact that the magnetic fields inferred from several
      observed properties of SGRs and AXPs are greater than-or at the high end of the
      range of-those of radio pulsars. In the peculiar case of SGR 0418+5729, a weak
      dipole magnetic moment is derived from its timing parameters, whereas a strong
      field has been proposed to reside in the stellar interior and in multipole
      components on the surface. Here we show that the X-ray spectrum of SGR 0418+5729
      has an absorption line, the properties of which depend strongly on the star's
      rotational phase. This line is interpreted as a proton cyclotron feature and its
      energy implies a magnetic field ranging from 2 * 10(14) gauss to more than 10(15)
      gauss.

PMID- 23955230
TI  - Deterministic quantum teleportation of photonic quantum bits by a hybrid
      technique.
AB  - Quantum teleportation allows for the transfer of arbitrary unknown quantum states
      from a sender to a spatially distant receiver, provided that the two parties
      share an entangled state and can communicate classically. It is the essence of
      many sophisticated protocols for quantum communication and computation. Photons
      are an optimal choice for carrying information in the form of 'flying qubits',
      but the teleportation of photonic quantum bits (qubits) has been limited by
      experimental inefficiencies and restrictions. Main disadvantages include the
      fundamentally probabilistic nature of linear-optics Bell measurements, as well as
      the need either to destroy the teleported qubit or attenuate the input qubit when
      the detectors do not resolve photon numbers. Here we experimentally realize fully
      deterministic quantum teleportation of photonic qubits without post-selection.
      The key step is to make use of a hybrid technique involving continuous-variable
      teleportation of a discrete-variable, photonic qubit. When the receiver's
      feedforward gain is optimally tuned, the continuous-variable teleporter acts as a
      pure loss channel, and the input dual-rail-encoded qubit, based on a single
      photon, represents a quantum error detection code against photon loss and hence
      remains completely intact for most teleportation events. This allows for a
      faithful qubit transfer even with imperfect continuous-variable entangled states:
      for four qubits the overall transfer fidelities range from 0.79 to 0.82 and all
      of them exceed the classical limit of teleportation. Furthermore, even for a
      relatively low level of the entanglement, qubits are teleported much more
      efficiently than in previous experiments, albeit post-selectively (taking into
      account only the qubit subspaces), and with a fidelity comparable to the
      previously reported values. 

PMID- 23955231
TI  - Deterministic quantum teleportation with feed-forward in a solid state system.
AB  - Engineered macroscopic quantum systems based on superconducting electronic
      circuits are attractive for experimentally exploring diverse questions in quantum
      information science. At the current state of the art, quantum bits (qubits) are
      fabricated, initialized, controlled, read out and coupled to each other in simple
      circuits. This enables the realization of basic logic gates, the creation of
      complex entangled states and the demonstration of algorithms or error correction.
      Using different variants of low-noise parametric amplifiers, dispersive quantum
      non-demolition single-shot readout of single-qubit states with high fidelity has
      enabled continuous and discrete feedback control of single qubits. Here we
      realize full deterministic quantum teleportation with feed-forward in a chip
      based superconducting circuit architecture. We use a set of two parametric
      amplifiers for both joint two-qubit and individual qubit single-shot readout,
      combined with flexible real-time digital electronics. Our device uses a crossed
      quantum bus technology that allows us to create complex networks with arbitrary
      connecting topology in a planar architecture. The deterministic teleportation
      process succeeds with order unit probability for any input state, as we prepare
      maximally entangled two-qubit states as a resource and distinguish all Bell
      states in a single two-qubit measurement with high efficiency and high fidelity.
      We teleport quantum states between two macroscopic systems separated by 6 mm at a
      rate of 10(4) s(-1), exceeding other reported implementations. The low
      transmission loss of superconducting waveguides is likely to enable the range of
      this and other schemes to be extended to significantly larger distances, enabling
      tests of non-locality and the realization of elements for quantum communication
      at microwave frequencies. The demonstrated feed-forward may also find application
      in error correction schemes.

PMID- 23955232
TI  - Tunable near-infrared and visible-light transmittance in nanocrystal-in-glass
      composites.
AB  - Amorphous metal oxides are useful in optical, electronic and electrochemical
      devices. The bonding arrangement within these glasses largely determines their
      properties, yet it remains a challenge to manipulate their structures in a
      controlled manner. Recently, we developed synthetic protocols for incorporating
      nanocrystals that are covalently bonded into amorphous materials. This
      'nanocrystal-in-glass' approach not only combines two functional components in
      one material, but also the covalent link enables us to manipulate the glass
      structure to change its properties. Here we illustrate the power of this approach
      by introducing tin-doped indium oxide nanocrystals into niobium oxide glass
      (NbOx), and realize a new amorphous structure as a consequence of linking it to
      the nanocrystals. The resulting material demonstrates a previously unrealized
      optical switching behaviour that will enable the dynamic control of solar
      radiation transmittance through windows. These transparent films can block near
      infrared and visible light selectively and independently by varying the applied
      electrochemical voltage over a range of 2.5 volts. We also show that the
      reconstructed NbOx glass has superior properties-its optical contrast is enhanced
      fivefold and it has excellent electrochemical stability, with 96 per cent of
      charge capacity retained after 2,000 cycles. 

PMID- 23955234
TI  - Visualizing cyclic peptide hydration at the single-molecule level.
AB  - The role of water molecules in the selective transport of potassium ions across
      cell membranes is important. Experimental investigations of valinomycin-water
      interactions remain huge challenge due to the poor solubility of valinomycin in
      water. Herein, we removed this experimental obstacle by introducing gaseous water
      and valinomycin onto a Cu(111) surface to investigate the hydration of
      valinomycin. By combining scanning tunneling microscopy (STM) with density
      functional theory (DFT) calculations, we revealed that water could affect the
      adsorption structure of valinomycin. Hydrogen bond interactions occurred
      primarily at the carbonyl oxygen of valinomycin and resulted in the formation of
      valinomycin hydrates. The single-molecule perspective revealed in our
      investigation could provide new insight into the role of water on the
      conformation transition of valinomycin, which might provide a new molecular basis
      for the ion transport mechanism at the water/membrane interface. 

PMID- 23955235
TI  - Dynamics of CD3+ T-cell distribution throughout the estrous cycle and gestation
      in the bovine endometrium.
AB  - T cells are the dominant lymphocytes in the endometrium and are considered to
      play a crucial role in implantation and in the maintenance of gestation through
      cytokine production and immune regulation. The mechanisms underlying
      immunoregulation at the feto-maternal interface are still obscure for this
      complex system. Understanding the role of T cells is a key factor in
      understanding the endometrial immune system. In this study, the distribution of
      endometrial CD3+ T cells in bovines was examined by immunohistochemical analysis.
      The estrous cycle and gestation was divided into 4 stages, and the number of CD3+
      positive T cells was counted in each stage. CD3+ cells were found in the
      endometrium in significant numbers throughout the estrous cycle and were mostly
      located in the subepithelial area. The number of CD3+ cells significantly
      increased in the early and mid-luteal phases but decreased after implantation
      with the progression of gestation. No T cells were found in the placentome or
      specifically in the tissues near the fetus, including the trophoblastic area. In
      addition, very few T cells were found in stromal regions close to the myometrium
      of the endometrium. These findings suggest that downregulation of bovine
      endometrial CD3+ T-cell functions is closely related to the successful
      maintenance of gestation in a spatiotemporal manner.

PMID- 23955236
TI  - Successful production of piglets derived from expanded blastocysts vitrified
      using a micro volume air cooling method without direct exposure to liquid
      nitrogen.
AB  - This study was conducted to clarify the feasibility of newly developed
      vitrification techniques for porcine embryos using the micro volume air cooling
      (MVAC) method without direct contact with liquid nitrogen (LN2). Expanded
      blastocysts were vitrified in a solution containing 6 M ethylene glycol, 0.6 M
      trehalose and 2% (wt/vol) polyethylene glycol in 10% HEPES-buffered PZM-5. The
      blastocysts were collected from gilts and vitrified using the new device (MVAC)
      or a Cryotop (CT). Blastocysts were stored in LN2 for at least 1 month. After
      warming, cryoprotective agents were removed using a single step. Survival of the
      embryos was assessed by in vitro culture (Experiment 1) and by embryo transfer to
      recipients (Experiment 2). In Experiment 1, the embryos vitrified by the MVAC or
      CT and fresh embryos without vitrification (Control) were used. The survival
      rates of embryos in the MVAC, CT and Control groups were 88.9% (32/36), 91.7%
      (33/36) and 100% (34/34), respectively, after 48 h culture, and the hatching
      rates of embryos after 48 h incubation were 69.4% (25/36), 63.9% (23/36) and
      94.1% (32/34), respectively. In Experiment 2, 64 vitrified embryos were
      transferred to 5 recipient gilts, and 8 healthy piglets were produced from 3
      recipients in the MVAC group. Similarly, 66 vitrified embryos were transferred to
      5 recipient gilts, and 9 healthy piglets were produced from 2 recipients in the
      CT group. These results indicated that porcine expanded blastocysts can be
      cryopreserved using the MVAC method without potential pathogen contamination from
      LN2.

PMID- 23955237
TI  - Post-death cloning of endangered Jeju black cattle (Korean native cattle):
      fertility and serum chemistry in a cloned bull and cow and their offspring.
AB  - To preserve Jeju black cattle (JBC; endangered native Korean cattle), a pair of
      cattle, namely a post-death cloned JBC bull and cow, were produced by somatic
      cell nuclear transfer (SCNT) in a previous study. In the present study, we
      examined the in vitro fertilization and reproductive potentials of these post
      death cloned animals. Sperm motility, in vitro fertilization and developmental
      capacity were examined in a post-death cloned bull (Heuk Oll Dolee) and an
      extinct nuclear donor bull (BK94-13). We assessed reproductive ability in another
      post-death cloned cow (Heuk Woo Sunee) using cloned sperm for artificial
      insemination (AI). There were no differences in sperm motility or developmental
      potential of in vitro fertilized embryos between the post-death cloned bull and
      its extinct nuclear donor bull; however, the embryo development ratio was
      slightly higher in the cloned sperm group than in the nuclear donor sperm group.
      After one attempt at AI, the post-death cloned JBC cow became pregnant, and
      gestation proceeded normally until day 287. From this post-death cloned sire and
      dam, a JBC male calf (Heuk Woo Dolee) was delivered naturally (weight, 25 kg).
      The genetic paternity/maternity of the cloned JBC bull and cow with regard to
      their offspring was confirmed using International Society for Animal Genetics
      standard microsatellite markers. Presently, Heuk Woo Dolee is 5 months of age and
      growing normally. In addition, there were no significant differences in blood
      chemistry among the post-death cloned JBC bull, the cow, their offspring and
      cattle bred by AI. This is the first report showing that a pair of cattle,
      namely, a post-death cloned JBC bull and cow, had normal fertility. Therefore,
      SCNT can be used effectively to increase the population of endangered JBC. 

PMID- 23955238
TI  - Performance evaluation of public non-profit hospitals using a BP artificial
      neural network: the case of Hubei Province in China.
AB  - To provide a reference for evaluating public non-profit hospitals in the new
      environment of medical reform, we established a performance evaluation system for
      public non-profit hospitals. The new "input-output" performance model for public
      non-profit hospitals is based on four primary indexes (input, process, output and
      effect) that include 11 sub-indexes and 41 items. The indicator weights were
      determined using the analytic hierarchy process (AHP) and entropy weight method.
      The BP neural network was applied to evaluate the performance of 14 level-3
      public non-profit hospitals located in Hubei Province. The most stable BP neural
      network was produced by comparing different numbers of neurons in the hidden
      layer and using the "Leave-one-out" Cross Validation method. The performance
      evaluation system we established for public non-profit hospitals could reflect
      the basic goal of the new medical health system reform in China. Compared with
      PLSR, the result indicated that the BP neural network could be used effectively
      for evaluating the performance public non-profit hospitals. 

PMID- 23955240
TI  - Metacognitive monitoring of attention performance and its influencing factors.
AB  - Metacognitive monitoring is a central element of metacognitive processing
      exerting widespread influences on information processing. Albeit being subject to
      numerous empirical investigations referring to memory performance, there is
      little research investigating metacognitive monitoring in other cognitive
      domains. The present study investigated in 45 healthy students whether factors
      that are known to influence monitoring of memory performance, i.e., task
      difficulty, time of assessment, and practice, also exhibit a significant impact
      on monitoring of attention performance. A multivariate analysis of variance with
      three within-subject repeated measures factors on two dependent variables
      (monitoring of (a) time, and (b) errors in an attention task) was conducted.
      Results showed that monitoring ability significantly decreased with increasing
      task difficulty, was significantly better for post than for pre-assessment, and
      significantly increased with practice. Therefore, results suggest that the
      examined factors influenced monitoring of attention performance equivalent to the
      influence of these factors found in metamemory research.

PMID- 23955239
TI  - Foodborne illness incidence rates and food safety risks for populations of low
      socioeconomic status and minority race/ethnicity: a review of the literature.
AB  - While foodborne illness is not traditionally tracked by race, ethnicity or
      income, analyses of reported cases have found increased rates of some foodborne
      illnesses among minority racial/ethnic populations. In some cases (Listeria,
      Yersinia) increased rates are due to unique food consumption patterns, in other
      cases (Salmonella, Shigella, Campylobacter) it is unclear why this health
      disparity exists. Research on safe food handling knowledge and behaviors among
      low income and minority consumers suggest that there may be a need to target safe
      food handling messages to these vulnerable populations. Another possibility is
      that these populations are receiving food that is less safe at the level of the
      retail outlet or foodservice facility. Research examining the quality and safety
      of food available at small markets in the food desert environment indicates that
      small corner markets face unique challenges which may affect the quality and
      potential safety of perishable food. Finally, a growing body of research has
      found that independent ethnic foodservice facilities may present increased risks
      for foodborne illness. This review of the literature will examine the current
      state of what is known about foodborne illness among, and food safety risks for,
      minority and low socioeconomic populations, with an emphasis on the United States
      and Europe. 

PMID- 23955242
TI  - Retraction: Severe aseptic leucoencephalopathy: Der Nervenarzt (2009) 80:1496
      1501.

PMID- 23955241
TI  - Neuroprotective activity of pDING in response to HIV-1 Tat.
AB  - Although neurons are not productively infected with HIV-1, neuronal injury and
      death are frequently seen in the brains of AIDS patients with neurological and
      neurocognitive disorders. Evidently, viral proteins including Tat and cellular
      inflammatory factors released by activated and/or infected microglia,
      macrophages, and astrocytes contribute to neuronal cell death. Several studies
      have demonstrated that HIV-1 associated neuronal cell injury is mediated by
      dysregulation of signaling pathways that are controlled, in part, by a class of
      serine/threonine kinases. In this study, we demonstrate that pDING, a novel plant
      derived phosphate binding protein has the capacity to reduce the severity of
      injury and death caused by HIV-1 and its neurotoxic Tat protein. We demonstrate
      that pDING, also called p27SJ/p38SJ, protects cells from the loss of neuronal
      processes induced by Tat and promotes neuronal outgrowth after Tat-mediated
      injury. Further, expression of pDING prevents Tat-induced oxidative stress and
      mitochondrial permeability. With its profound phosphatase activity, pDING
      controls the activity of several kinases including MAPK, Cdk5, and their
      downstream target protein, MEF2, which is implicated in neuronal cell protection.
      Our results show that expression of pDING in neuronal cells diminishes the level
      of hyperphosphorylated forms of Cdk5 and MEF2 caused by Tat and the other
      neurotoxic agents that are secreted by the HIV-1 infected cells. These
      observations suggest that pDING, through its phosphatase activity, has the
      ability to manipulate the state of phosphorylation and activity of several
      factors involved in neuronal cell health in response to HIV-1.

PMID- 23955246
TI  - Overcoming perceptions of financial barriers to rotavirus vaccine introduction in
      Asia.
AB  - Despite a WHO recommendation in 2009, reaffirmed in 2013, that all countries
      should consider introducing rotavirus vaccines into their National Immunization
      Programs, as of June 2013 only 45 have done so. One major consideration appears
      to have been the costs of the vaccine to countries. Of concern, is that Asian
      countries have been slow to introduce rotavirus vaccines despite having robust
      data that could inform the decision-making process. Although decisions on new
      vaccine introduction are very complex and vary by country and region, economic
      evaluations are often pivotal once vaccine efficacy and safety has been
      established, and disease burden documented and communicated. Unfortunately, with
      private sector list prices of vaccines often used in economic evaluations, rather
      than a potential public health sector pricing structure, policy-makers may defer
      decisions on rotavirus vaccine introduction based on the belief that "the vaccine
      price is too high," even though this might be based on erroneous data. The Pan
      American Health Organization's Revolving Fund provides one example of how vaccine
      price can be made more competitive and transparent through a regional tendering
      process. Other mechanisms, such as tiered pricing and UNICEF procurement, also
      exist that could help Asian and other countries move forward more quickly with
      rotavirus vaccine introduction. 

PMID- 23955247
TI  - Life-prolonging measures for a dead theory?
AB  - In a recent review article, Selman and colleagues (Trends Ecol Evol 27:570-577,
      2012) discuss the status quo of the oxidative stress theory of aging (OSTA) and
      how it links to life history evolution. They suggest that the OSTA should be
      tested in wild populations which might show effects masked in laboratory
      settings. We disagree with their propositions for several reasons. We argue that
      there is increasing evidence that reactive oxygen species (ROS) are not causally
      linked with aging and that ROS do not play a straightforward role in shaping life
      history evolution. We propose that laboratory animals and semi-wild populations
      rather than wild animals are suited best to test any hypothesized effect of
      reactive oxygen species. This is because data from controlled manipulative
      experiments rather than observational correlations are preferred to solve this
      issue. In addition, nonconventional model organisms will be useful in answering
      the question how relevant the OSTA could be for life history evolution. 

PMID- 23955248
TI  - Does part-time sick leave help individuals with mental disorders recover lost
      work capacity?
AB  - PURPOSE: This paper aims to answer the question whether combining sick leave with
      some hours of work can help employees diagnosed with a mental disorder (MD)
      increase their probability of returning to work. Given the available data, this
      paper analyzes the impact of part-time sick leave (PTSL) on the probability of
      fully recovering lost work capacity for employees diagnosed with an MD. METHODS:
      The effects of PTSL on the probability of fully recovering lost work capacity are
      estimated by a discrete choice one-factor model using data on a nationally
      representative sample extracted from the register of the National Agency of
      Social Insurance in Sweden and supplemented with information from questionnaires.
      All individuals in the sample were 20-64 years old and started a sickness spell
      of at least 15 days between 1 and 16 February 2001. We selected all employed
      individuals diagnosed with an MD, with a final sample of 629 individuals.
      RESULTS: The results show that PTSL is associated with a low likelihood of full
      recovery, yet the timing of the assignment is important. PTSL's effect is
      relatively low (0.015) when it is assigned in the beginning of the spell but
      relatively high (0.387), and statistically significant, when assigned after 60
      days of full-time sick leave (FTSL). This suggests efficiency improvements from
      assigning employees with an MD diagnosis, when possible, to PTSL. CONCLUSIONS:
      The employment gains will be enhanced if employees with an MD diagnosis are
      encouraged to return to work part-time after 60 days or more of FTSL.

PMID- 23955249
TI  - Physiological responses to nanoCuO in fungi from non-polluted and metal-polluted
      streams.
AB  - Nanocopper oxide (nanoCuO) is among the most widely used metal oxide
      nanoparticles which increases their chance of being released into freshwaters.
      Fungi are the major microbial decomposers of plant litter in streams. Fungal
      laccases are multicopper oxidase enzymes that are involved in the degradation of
      lignin and various xenobiotic compounds. We investigated the effects of nanoCuO
      (5 levels, <= 200 mg L(-1)) on four fungal isolates collected from metal-polluted
      and non-polluted streams by analyzing biomass production, changes in mycelial
      morphology, laccase activity, and quantifying copper adsorbed to mycelia, and
      ionic and nanoparticulate copper in the growth media. The exposure to nanoCuO
      decreased the biomass produced by all fungi in a concentration- and time
      dependent manner. Inhibition of biomass production was stronger in fungi from non
      polluted (EC50(10 days) <= 31 mg L(-1)) than from metal-polluted streams (EC50(10
      days) >= 65.2 mg L(-1)). NanoCuO exposure led to cell shrinkage and mycelial
      degeneration, particularly in fungi collected from non-polluted streams.
      Adsorption of nanoCuO to fungal mycelia increased with the concentration of
      nanoCuO in the medium and was higher in fungi from non-polluted streams.
      Extracellular laccase activity was induced by nanoCuO in two fungal isolates in a
      concentration-dependent manner, and was highly correlated with adsorbed Cu and/or
      ionic Cu released by dissolution from nanoCuO. Putative laccase gene fragments
      were also detected in these fungi. Lack of substantial laccase activity in the
      other fungal isolates was corroborated by the absence of laccase-like gene
      fragments.

PMID- 23955250
TI  - Temporal trends in "legacy" organochlorine contaminants in blubber of ringed
      seals (Phoca hispida) from Ulukhaktok, NT, Canada between 1972 and 2010.
AB  - In blubber of ringed seals (Phoca hispida) from Ulukhaktok, NT, residues of DDT,
      other organochlorine pesticides, and PCBs declined between 1972 and 2010. The
      rate of decline varied: concentrations of the DDT-group began to fall after 1981,
      whereas those of PCBs fell rapidly between 1972 and 1981, and then slowed.
      Concentrations of cis- and trans-chlordane and of HCB in both sexes, and of cis
      nonachlor in males, declined slowly between 1978 and 2010; those of other
      organochlorine pesticides remained steady. Exponential half-lives of p,p'-DDT and
      p,p'-DDE in female seals are about 9 and 36 y (corresponding to initial declines
      of 7.8% and 1.9% per year, respectively) and those of PCB congeners from about 20
      to 60 y (declines of 3.2% to <1.5% per year); the more refractory residues may be
      detectable for centuries to come. Exploratory PCA of PCB congener distribution
      identified temporal changes apparently not related to molecular structure.

PMID- 23955251
TI  - A review of background dioxin concentrations in urban/suburban and rural soils
      across the United States: implications for site assessments and the establishment
      of soil cleanup levels.
AB  - Over the last several decades, dioxin releases have decreased >90%, leading to a
      corresponding decrease in human body burdens. In addition, the weight-of-evidence
      indicates that soil exposures have little impact on human body burdens of dioxin
      like compounds (DLCs), with dietary sources being the greatest contributor. In
      spite of this, USEPA recently proposed substantially lower preliminary
      remediation goals (PRGs) for soil based on their new oral reference dose (RfD)
      for dioxin. As such, it is important to understand how these lower soil PRGs
      compare to background concentrations in urban/suburban and rural soils. The
      objective of this evaluation was to conduct a comprehensive review of available
      data concerning background levels of DLCs in U.S. soils. There was substantial
      variability in how the soil dioxin data were presented (e.g., raw vs. summary
      data, congener vs. toxic equivalency [TEQ] concentration, number of DLC congeners
      reported, etc.). In cases where TEQ estimates were based on outdated TEFs and
      congener-specific data was provided, TEQ concentrations were recalculated using
      the current WHO2006 TEFs. The data available for rural soils were generally more
      robust than for urban/suburban soils. Not surprisingly, background levels of DLCs
      in urban/suburban soils were higher and more variable than in rural soils: 0.1
      186 vs. 0.1-22.9 ng/kg TEQ, respectively. In several cases, incomplete soil DLC
      data were available (e.g., DL-PCBs not included) and, as such, calculated TEQ
      concentrations likely underestimate actual background levels. Though the current
      data are somewhat limited, these findings indicate that background DLC
      concentrations in urban/suburban soils may exceed the USEPA's updated PRGs based
      on the oral RfD, and are expected to substantially exceed future PRGs to be
      developed based on the forthcoming dioxin cancer slope factor. This demonstrates
      a need to characterize anthropogenic background DLCs in non-rural areas across
      the US to avoid establishing soil screening levels and PRGs that are lower than
      background concentrations.

PMID- 23955252
TI  - Submerged arc furnace process superior to the Waelz process in reducing PCDD/F
      emission during thermal treatment of electric arc furnace dust.
AB  - Besides the Waelz process, the submerged arc furnace (SAF) process has also been
      extensively used to retain metals from ashes and scraps in the metallurgical
      industry. However, very little is known about the formation and depletion of
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from this thermal
      process. In this study, an electric arc furnace (EAF) dust treatment plant
      adopting the SAF process was investigated and compared to the plant adopting the
      Waelz process. The predominant contributor of PCDD/F I-TEQ input was the EAF
      dusts, accounting for 98.4% of the total. The PCDD/F contents in the generated
      fly ashes of the SAF were extremely low, as almost all the organic compounds for
      PCDD/F formation were decomposed by the high operating temperatures (1500-1700 
      degrees C) of the SAF. Therefore, the PCDD/F emission factor of the SAF process
      (46.9 MUg I-TEQ/tonne-EAF dust) was significantly lower than that of the Waelz
      process (840-1120 MUg I-TEQ/tonne-EAF dust). Its PCDD/F output/input ratios (0.23
      and 0.50 based on mass and toxicity) were also lower than those of the Waelz
      process plant (0.62 and 1.19). Therefore, the SAF process is superior to the
      Waelz process in reducing the potential of PCDD/F formation.

PMID- 23955253
TI  - Influence of ions on the coagulation and removal of fullerene in aqueous phase.
AB  - Increased attention has been paid to the transportation and removal efficiencies
      of nanoparticles during water treatment. Here, C60 was selected as nano-pollutant
      to investigate its removal efficiency in the process of coagulation by Al(3+) in
      regard to different ions. Negatively charged C60 tends to adsorb hydrated Al(3+)
      to form positively charged C60-Al(OH)(n)((m-delta)+) particles, leading to the
      restabilization of C60. Multivalent anions, i.e., CO3(2-), SO4(2-), HPO4(2-),and
      humic acid (HA), were shown to bridge the C60-Al (OH)(n)((m-delta)+) particles
      together and induce the formation of flocs, resulting in enhanced C60 removal
      (>80%). Monovalent anions, such as OH(-), NO3(-) and the surfactant SDS, were not
      able to bridge the C60-Al (OH)(n)((m-delta)+) particles together; hence, they had
      no effect on the C60 removal. The addition of Na(+) and Ca(2+) increased the
      ionic strength of the aqueous solution, which compressed the electric double
      layer and induced the C60-Al(OH)(n)((m-delta)+) particles to aggregate. However,
      they are not the essential factors for flocs formation. This is the first study
      to report the bridging phenomena between multivalent anions and C60-Al(OH)(n)((m
      delta)+) in water treatments, and it highlights that the presence of multivalent
      anions and cations in raw water are important for the effective removal of C60.

PMID- 23955254
TI  - Parenting and Family Adjustment Scales (PAFAS): validation of a brief parent
      report measure for use in assessment of parenting skills and family
      relationships.
AB  - This study examined the psychometric characteristics of the Parent and Family
      Adjustment Scales (PAFAS). The PAFAS was designed as a brief outcome measure for
      assessing changes in parenting practices and parental adjustment in the
      evaluation of both public health and individual or group parenting interventions.
      The inventory consists of the Parenting scale measuring parenting practices and
      quality of parent-child relationship and of the Family Adjustment scale measuring
      parental emotional adjustment and partner and family support in parenting. Two
      studies were conducted to validate the inventory. A sample of 370 parents
      participated in Study 1 and a sample of 771 parents participated in Study 2.
      Children's ages ranged from 2 to 12 years old. In Study 1 confirmatory factor
      analysis supported an 18-item, four factor model of PAFAS Parenting, and a 12
      item, three factor model of PAFAS Family Adjustment. Psychometric evaluation of
      the PAFAS revealed that the scales had good internal consistency, as well as
      satisfactory construct and predictive validity. In Study 2 confirmatory factor
      analysis supported stability of the factor structures of PAFAS Parenting and
      PAFAS Family Adjustment revealed in Study 1. Potential uses of the measure and
      implications for future validation studies are discussed. 

PMID- 23955256
TI  - Regioselective palladium-catalyzed intramolecular oxidative aminofluorination of
      unactivated alkenes.
AB  - A novel Pd-catalyzed regioselective intramolecular aminofluorination of
      unactivated alkenes has been developed, which is an efficient method for the
      synthesis of a variety of monofluoromethylated nitrogen-containing heterocycles. 

PMID- 23955255
TI  - Tales from previous times: important eponyms in pediatric surgery.
AB  - The use of eponyms in medicine has a long and captivating tradition, which
      applies to pediatric surgery as well. Unfortunately, even though these eponyms
      are widely used, oftentimes the fascinating personalities and lives behind these
      names remain unrecognized or underappreciated, especially among residents,
      fellows and younger-generation pediatric surgeons. Therefore, in this article, we
      review 15 names that are frequently used as eponyms in modern pediatric surgery
      and hereby enlighten the personalities behind them. Given their particular
      frequency, we choose the following eponyms: Ramstedt pylorotomy, Nissen
      fundoplication, Murphy's sign and sequence, McBurney's sign and incision,
      Meckel's diverticulum, Kasai portoenterostomy, Ladd's procedure, Morgagni and
      Bochdalek hernia, Ravitch operation, Nuss procedure, Hirschsprung disease,
      Swenson pullthrough, Pena procedure and Wilms tumor. A detailed description of
      the historical importance of these personalities and their contribution to our
      field is given. Without the appropriate historical background, it is difficult
      for the current younger and next generation pediatric surgeons to grasp the full
      spectrum of the ongoing progress in our field. Therefore, our article conveys not
      only important insight into the past, but also provides young surgeons with an
      important historical perspective essential to understand the current and future
      developments in modern pediatric surgery.

PMID- 23955257
TI  - Prognostic implications of EGFR and HER-2 alteration assessed by
      immunohistochemistry and silver in situ hybridization in gastric cancer patients
      following curative resection.
AB  - BACKGROUND: The aim of this study was to use immunohistochemistry (IHC) and
      silver in situ hybridization (SISH) to evaluate alterations in EGFR and HER2 in
      gastric cancer in order to determine the relationship with prognosis in gastric
      cancer patients following curative resection. PATIENTS AND METHODS: In this
      study, we analyzed EGFR and HER-2 status by IHC and SISH in 254 stage I-III
      gastric cancer patients who underwent curative surgery. RESULTS: Thirteen cases
      (2.48 %) showed EGFR alteration by IHC or SISH. EGFR alteration was associated
      with older age (P = 0.021), intestinal type (P = 0.040) and higher stage disease
      (P < 0.001). The patients with operable state gastric cancer who had EGFR
      alteration had an unfavorable prognosis, and multivariate analysis confirmed that
      EGFR alteration was an independent unfavorable prognostic factor. Twenty-seven
      cases (10.6 %) showed HER-2 alteration by IHC or SISH. HER-2 alteration was
      associated with older age (P = 0.006), well or moderately differentiated
      histology (P < 0.001) and intestinal type (P = 0.002). CONCLUSION: HER-2
      alteration is not an independent prognostic factor for curatively resectable
      gastric cancer. We observed EGFR alteration in a subset of cases with operable
      state gastric cancer and determined that it was associated with an unfavorable
      prognosis.

PMID- 23955258
TI  - Surgical technique: Gluteus maximus and tensor fascia lata transfer for primary
      deficiency of the abductors of the hip.
AB  - BACKGROUND: Avulsion of the abductor muscles of the hip may cause severe limp and
      pain. Limited literature is available on treatment approaches for this problem,
      and each has shortcomings. This study describes a muscle transfer technique to
      treat complete irreparable avulsion of the hip abductor muscles and tendons.
      DESCRIPTION OF TECHNIQUE: Ten adult cadaver specimens were dissected to determine
      nerve and blood supply point of entry in the gluteus maximus and tensor fascia
      lata (TFL) and evaluate the feasibility and safety of transferring these muscles
      to substitute for the gluteus medius and minimus. In this technique, the anterior
      portion of the gluteus maximus and the entire TFL are mobilized and transferred
      to the greater trochanter such that the muscle fiber direction of the transferred
      muscles closely matches that of the gluteus medius and minimus. METHODS: Five
      patients (five hips) were treated for primary irreparable disruption of the hip
      abductor muscles using this technique between January 2008 and April 2011. All
      patients had severe or moderate pain, severe abductor limp, and positive
      Trendelenburg sign. Patients were evaluated for pain and function at a mean of 28
      months (range, 18-60 months) after surgery. RESULTS: All patients could actively
      abduct 3 months postoperatively. At 1 year postoperatively, three patients had no
      hip pain, two had mild pain that did not limit their activity, three had no limp,
      and one had mild limp. One patient fell, fractured his greater trochanter, and
      has persistent limp and abduction weakness. CONCLUSIONS: The anterior portion of
      the gluteus maximus and the TFL can be transferred to the greater trochanter to
      substitute for abductor deficiency. In this small series, the surgical procedure
      was reproducible and effective; further studies with more patients and longer
      followup are needed to confirm this.

PMID- 23955259
TI  - CORR Insights (r): Image guided core needle biopsy of musculoskeletal lesions:
      are nondiagnostic results clinically useful?

PMID- 23955260
TI  - Minimally invasive transforaminal lumbar interbody fusion for spondylolisthesis
      and degenerative spondylosis: 5-year results.
AB  - BACKGROUND: Multiple studies have reported favorable short-term results after
      treatment of spondylolisthesis and other degenerative lumbar diseases with
      minimally invasive transforaminal lumbar interbody fusion. However, to our
      knowledge, results at a minimum of 5 years have not been reported.
      QUESTIONS/PURPOSES: We determined (1) changes to the Oswestry Disability Index,
      (2) frequency of radiographic fusion, (3) complications and reoperations, and (4)
      the learning curve associated with minimally invasive transforaminal lumbar
      interbody fusion at minimum 5-year followup. METHODS: We reviewed our first 124
      patients who underwent minimally invasive transforaminal lumbar interbody fusion
      to treat low-grade spondylolisthesis and degenerative lumbar diseases and did not
      need a major deformity correction. This represented 63% (124 of 198) of the
      transforaminal lumbar interbody fusion procedures we performed for those
      indications during the study period (2003-2007). Eighty-three (67%) patients had
      complete 5-year followup. Plain radiographs and CT scans were evaluated by two
      reviewers. Trends of surgical time, blood loss, and hospital stay over time were
      examined by logarithmic curve fit-regression analysis to evaluate the learning
      curve. RESULTS: At 5 years, mean Oswestry Disability Index improved from 60
      points preoperatively to 24 points and 79 of 83 patients (95%) had improvement of
      greater than 10 points. At 5 years, 67 of 83 (81%) achieved radiographic fusion,
      including 64 of 72 patients (89%) who had single-level surgery. Perioperative
      complications occurred in 11 of 124 patients (9%), and another surgical procedure
      was performed in eight of 124 patients (6.5%) involving the index level and seven
      of 124 patients (5.6%) at adjacent levels. There were slowly decreasing trends of
      surgical time and hospital stay only in single-level surgery and almost no change
      in intraoperative blood loss over time, suggesting a challenging learning curve.
      CONCLUSIONS: Oswestry Disability Index scores improved for patients with
      spondylolisthesis and degenerative lumbar diseases treated with minimally
      invasive transforaminal lumbar interbody fusion at minimum 5-year followup. We
      suggest this procedure is reasonable for properly selected patients with these
      indications; however, traditional approaches should still be performed for
      patients with high-grade spondylolisthesis, patients with a severely collapsed
      disc space and no motion seen on the dynamic radiographs, patients who need
      multilevel decompression and arthrodesis, and patients with kyphoscoliosis
      needing correction. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the
      Instructions for Authors for a complete description of levels of evidence.

PMID- 23955262
TI  - Surgical management of basilar artery laceration caused by transorbital
      penetrating injury: case report.
AB  - Transorbital penetrating injuries are rare and present with a heterogeneity of
      intracranial injury patterns that require individualized therapeutic procedures.
      In this report, we describe the case of a distal basilar artery laceration in a
      16-month-old boy caused by accidental transorbital penetration with a pencil.
      Surgical removal of the pencil was performed, but hemostasis could only be
      achieved by clipping the impaired vessel. Adequate diagnostics and an
      individualized surgical strategy are necessary to deal with these life
      threatening injuries. 

PMID- 23955261
TI  - Mutant ataxin-3 with an abnormally expanded polyglutamine chain disrupts
      dendritic development and metabotropic glutamate receptor signaling in mouse
      cerebellar Purkinje cells.
AB  - Spinocerebellar ataxia type 3 (SCA3) is caused by the abnormal expansion of CAG
      repeats within the ataxin-3 gene. Previously, we generated transgenic mice (SCA3
      mice) that express a truncated form of ataxin-3 containing abnormally expanded
      CAG repeats specifically in cerebellar Purkinje cells (PCs). Here, we further
      characterize these SCA3 mice. Whole-cell patch-clamp analysis of PCs from
      advanced-stage SCA3 mice revealed a significant decrease in membrane capacitance
      due to poor dendritic arborization and the complete absence of metabotropic
      glutamate receptor subtype1 (mGluR1)-mediated retrograde suppression of synaptic
      transmission at parallel fiber terminals, with an overall preservation of AMPA
      receptor-mediated fast synaptic transmission. Because these cerebellar phenotypes
      are reminiscent of retinoic acid receptor-related orphan receptor alpha
      (RORalpha)-defective staggerer mice, we examined the levels of RORalpha in the
      SCA3 mouse cerebellum by immunohistochemistry and found a marked reduction of
      RORalpha in the nuclei of SCA3 mouse PCs. To confirm that the defects in SCA3
      mice were caused by postnatal deposition of mutant ataxin-3 in PCs, not by genome
      disruption via transgene insertion, we tried to reduce the accumulation of mutant
      ataxin-3 in developing PCs by viral vector-mediated expression of CRAG, a
      molecule that facilitates the degradation of stress proteins. Concomitant with
      the removal of mutant ataxin-3, CRAG-expressing PCs had greater numbers of
      differentiated dendrites compared to non-transduced PCs and exhibited retrograde
      suppression of synaptic transmission following mGluR1 activation. These results
      suggest that postnatal nuclear accumulation of mutant ataxin-3 disrupts dendritic
      differentiation and mGluR-signaling in SCA3 mouse PCs, and this disruption may be
      caused by a defect in a RORalpha-driven transcription pathway. 

PMID- 23955263
TI  - Neuronavigation with the universal probe to access intracranial targets.
AB  - INTRODUCTION: The universal probe is a tool devised to allow navigation-directed
      biopsies and drainage procedures to be performed in a simple manner using a
      single hardware and software. AIM: To assess the efficacy and safety of the
      universal probe. RESULTS: We used the universal probe in a total of 17 patients
      for 10 biopsies and 8 drainage procedures. We were able to achieve our set
      objectives in all 18 procedures. We did not encounter any complications using
      this device. CONCLUSION: The universal probe enabled a variety of navigation
      based procedures to be carried out using only a single software and hardware.

PMID- 23955264
TI  - Structure and phylogenetic diversity of post-fire ectomycorrhizal communities of
      maritime pine.
AB  - Environmental disturbances define the diversity and assemblage of species,
      affecting the functioning of ecosystems. Fire is a major disturbance of
      Mediterranean pine forests. Pines are highly dependent on the ectomycorrhizal
      (EM) fungal symbiosis, which is critical for tree recruitment under primary
      succession. To determine the effects of time since fire on the structure and
      recovery of EM fungal communities, we surveyed the young Pinus pinaster
      regenerate in three sites differing in the elapsed time after the last fire
      event. Pine roots were collected, and EM fungi characterized by sequencing the
      internal transcribed spacer (ITS) and the large subunit (LSU) regions of the
      nuclear ribosomal (nr)-DNA. The effects of the elapsed time after fire on the EM
      community structure (richness, presence/absence of fungi, phylogenetic diversity)
      and on soil properties were analysed.Fungal richness decreased with the elapsed
      time since the fire; although, the phylogenetic diversity of the EM community
      increased. Soil properties were different depending on the elapsed time after
      fire and particularly, the organic matter, carbon-to-nitrogen (C/N) ratio,
      nitrogen and iron significantly correlated with the assemblage of fungal species.
      Ascomycetes, particularly Tuberaceae and Pezizales, were significantly over
      represented on saplings in the burned site. On seedlings, a significant over
      representation of Rhizopogonaceae and Atheliaceae was observed in the most
      recently burned site, while other fungi (i.e. Cortinariaceae) were significantly
      under-represented. Our results are consistent with the hypothesis that fire can
      act as a selective agent by printing a phylogenetic signal on the EM fungal
      communities associated with naturally regenerated pines, pointing out to some
      groups as potential fire-adapted fungi. 

PMID- 23955265
TI  - Protein structures among bio-ethanol co-products and its relationships with
      ruminal and intestinal availability of protein in dairy cattle.
AB  - The objectives of this study were to reveal molecular structures of protein among
      different types of the dried distillers grains with solubles (100% wheat DDGS
      (WDDGS); DDGS blend1 (BDDGS1, corn to wheat ratio 30:70%); DDGS blend2 (BDDGS2,
      corn to wheat ratio 50:50 percent)) and different batches within DDGS type using
      diffuse reflectance infrared Fourier transform spectroscopy (DRIFT). Compared
      with BDDGS1 and BDDGS2, wheat DDGS had higher (p < 0.05) peak area intensities of
      protein amide I and II and amide I to II intensity ratio. Increasing the corn to
      wheat ratio form 30:70 to 50:50 in the blend DDGS did not affect amide I and II
      area intensities and their ratio. Amide I to II peak intensity ratio differed (p
      < 0.05) among the different batches within WDDGS and BDDGS1. Compared with both
      blend DDGS types, WDDGS had higher alpha-helix and beta-sheet ratio (p < 0.05),
      while alpha-helix to beta-sheet ratio was similar among the three DDGS types. The
      alpha-helix to beta-sheet ratio differed significantly among batches within
      WDDGS. Principal component analysis (PCA) revealed that protein molecular
      structures in WDDGS differed from those of BDDGS1 and between different batches
      within BDDGS1 and BDDGS2. The alpha-helix to beta-sheet ratios of protein in all
      DDGS types had an influence on availability of protein at the ruminal level as
      well as at the intestinal level. The alpha-helix to beta-sheet ratio was
      positively correlated to rumen undegraded protein (r = 0.41, p < 0.05) and
      unavailable protein (PC; r = 0.59, p < 0.05). 

PMID- 23955267
TI  - Trastuzumab-Peptide interactions: mechanism and application in structure-based
      ligand design.
AB  - Understanding of protein-ligand interactions and its influences on protein
      stability is necessary in the research on all biological processes and
      correlative applications, for instance, the appropriate affinity ligand design
      for the purification of bio-drugs. In this study, computational methods were
      applied to identify binding site interaction details between trastuzumab and its
      natural receptor. Trastuzumab is an approved antibody used in the treatment of
      human breast cancer for patients whose tumors overexpress the HER2 (human
      epidermal growth factor receptor 2) protein. However, rational design of affinity
      ligands to keep the stability of protein during the binding process is still a
      challenge. Herein, molecular simulations and quantum mechanics were used on
      protein-ligand interaction analysis and protein ligand design. We analyzed the
      structure of the HER2-trastuzumab complex by molecular dynamics (MD) simulations.
      The interaction energies of the mutated peptides indicate that trastuzumab binds
      to ligand through electrostatic and hydrophobic interactions. Quantitative
      investigation of interactions shows that electrostatic interactions play the most
      important role in the binding of the peptide ligand. Prime/MM-GBSA calculations
      were carried out to predict the binding affinity of the designed peptide ligands.
      A high binding affinity and specificity peptide ligand is designed rationally
      with equivalent interaction energy to the wild-type octadecapeptide. The results
      offer new insights into affinity ligand design. 

PMID- 23955266
TI  - Gene expression profiling as a tool to investigate the molecular machinery
      activated during hippocampal neurodegeneration induced by trimethyltin (TMT)
      administration.
AB  - Trimethyltin (TMT) is an organotin compound exhibiting neurotoxicant effects
      selectively localized in the limbic system and especially marked in the
      hippocampus, in both experimental animal models and accidentally exposed humans.
      TMT administration causes selective neuronal death involving either the granular
      neurons of the dentate gyrus or the pyramidal cells of the Cornu Ammonis, with a
      different pattern of localization depending on the different species studied or
      the dosage schedule. TMT is broadly used to realize experimental models of
      hippocampal neurodegeneration associated with cognitive impairment and temporal
      lobe epilepsy, though the molecular mechanisms underlying the associated
      selective neuronal death are still not conclusively clarified. Experimental
      evidence indicates that TMT-induced neurodegeneration is a complex event
      involving different pathogenetic mechanisms, probably acting differently in
      animal and cell models, which include neuroinflammation, intracellular calcium
      overload, and oxidative stress. Microarray-based, genome-wide expression analysis
      has been used to investigate the molecular scenario occurring in the TMT-injured
      brain in different in vivo and in vitro models, producing an overwhelming amount
      of data. The aim of this review is to discuss and rationalize the state-of-the
      art on TMT-associated genome wide expression profiles in order to identify
      comparable and reproducible data that may allow focusing on significantly
      involved pathways. 

PMID- 23955268
TI  - Design, synthesis and DNA interaction study of new potential DNA bis
      intercalators based on glucuronic acid.
AB  - A series of novel potential DNA bis-intercalators were designed and synthesized,
      in which two glucuronic acids were linked by ethylenediamine, and the glucuronic
      acid was coupled with various chromophores, including quinoline, acridine, indole
      and purine, at the C-1 position. The preliminary binding properties of these
      compounds to calf thymus DNA (CT-DNA) have been investigated by UV-absorption and
      fluorescence spectroscopy. The results indicated that all the target compounds
      can interact with CT-DNA, and the acridine derivative, 3b, showed the highest key
      selection vector (KSV) value, which suggested that compound 3b binds most
      strongly to CT-DNA. 

PMID- 23955269
TI  - Tuberculous peritonitis with infracarinal mass and elevated CA-125 in a 13-year
      old girl.
AB  - A 13-year-old girl with weight loss and ascites was admitted with suspicion of a
      malignant disease. Abdominal magnetic resonance imaging indicated extensive
      peritonitis and showed no evidence of a solid tumor. As a new imaging
      observation, thoracic computed tomography showed a lymphoma-like infracarinal
      mass and further enlarged lymph nodes in the pathway of draining lymph ducts. A
      tuberculin skin test and an interferon-gamma blood test were positive, and the
      tumor marker CA-125 was elevated. Histology of a peritoneal biopsy showed
      infectious granulomas with central necrosis, and Mycobacterium tuberculosis could
      be cultured, leading to the diagnosis of a tuberculous peritonitis. The girl
      received multi-drug anti-tuberculous treatment and subsequently recovered. At
      follow-up the peritonitis and the infracarinal mass had vanished. In conclusion,
      tuberculous peritonitis is a rare but relevant differential diagnosis in
      peritonitis of unknown origin. Its diagnosis is facilitated by imaging, by
      tuberculosis skin and blood tests, and by clinical interpretation. 

PMID- 23955271
TI  - Clinical study report on milk production in the offspring of a somatic cell
      cloned Holstein cow.
AB  - This study examined two female offspring of a somatic cell cloned Holstein cow
      that had reproduction problems and milk production performance issues. The two
      offspring heifers, which showed healthy appearances and normal reproductive
      characteristics, calved on two separate occasions. The mean milk yields of the
      heifers in the first lactation period were 9,037 kg and 7,228 kg. The relative
      mean milk yields of these cows were 111.2% and 88.9%, respectively, when compared
      with that of the control group. No particular clinical abnormalities were
      revealed in milk yields and milk composition rate [e.g., fat, protein and solids
      not-fat (SNF)], and reproductive characteristics of the offspring of the somatic
      cell cloned Holstein cow suggested that the cloned offspring had normal milk
      production. 

PMID- 23955270
TI  - Fast and high-accuracy localization for three-dimensional single-particle
      tracking.
AB  - We report a non-iterative localization algorithm that utilizes the scaling of a
      three-dimensional (3D) image in the axial direction and focuses on evaluating the
      radial symmetry center of the scaled image to achieve the desired single-particle
      localization. Using this approach, we analyzed simulated 3D particle images by
      wide-field microscopy and confocal microscopy respectively, and the 3D trajectory
      of quantum dots (QDs)-labeled influenza virus in live cells. Both applications
      indicate that the method can achieve 3D single-particle localization with a sub
      pixel precision and sub-millisecond computation time. The precision is almost the
      same as that of the iterative nonlinear least-squares 3D Gaussian fitting method,
      but with two orders of magnitude higher computation speed. This approach can
      reduce considerably the time and costs for processing the large volume data of 3D
      images for 3D single-particle tracking, which is especially suited for 3D high
      precision single-particle tracking, 3D single-molecule imaging and even new
      microscopy techniques. 

PMID- 23955272
TI  - Synthesis of lanthanide-doped NaYF4@TiO2 core-shell composites with highly
      crystalline and tunable TiO2 shells under mild conditions and their upconversion
      based photocatalysis.
AB  - NaYF4:Yb,Tm@TiO2 core-shell composites were synthesized via a facile hydrothermal
      method. The highly crystalline TiO2 shell can be uniformly coated onto lanthanide
      doped NaYF4 microrods and nanorods under mild conditions without calcination. The
      thickness of the TiO2 shell can be tuned by varying the ratio of fluoride rods
      and Ti precursors. The microcomposite with a moderate TiO2 shell shows excellent
      photocatalytic activity under near-infrared irradiation.

PMID- 23955273
TI  - Mechanism-based epigenetic chemosensitization therapy of diffuse large B-cell
      lymphoma.
AB  - Although aberrant DNA methylation patterning is a hallmark of cancer, the
      relevance of targeting DNA methyltransferases (DNMT) remains unclear for most
      tumors. In diffuse large B-cell lymphoma (DLBCL) we observed that chemoresistance
      is associated with aberrant DNA methylation programming. Prolonged exposure to
      low-dose DNMT inhibitors (DNMTI) reprogrammed chemoresistant cells to become
      doxorubicin sensitive without major toxicity in vivo. Nine genes were recurrently
      hypermethylated in chemoresistant DLBCL. Of these, SMAD1 was a critical
      contributor, and reactivation was required for chemosensitization. A phase I
      clinical study was conducted evaluating azacitidine priming followed by standard
      chemoimmunotherapy in high-risk patients newly diagnosed with DLBCL. The
      combination was well tolerated and yielded a high rate of complete remission. Pre
      and post-azacitidine treatment biopsies confirmed SMAD1 demethylation and
      chemosensitization, delineating a personalized strategy for the clinical use of
      DNMTIs. SIGNIFICANCE: The problem of chemoresistant DLBCL remains the most urgent
      challenge in the clinical management of patients with this disease. We describe a
      mechanism-based approach toward the rational translation of DNMTIs for the
      treatment of high-risk DLBCL.

PMID- 23955274
TI  - Conditional targeted genome editing using somatically expressed TALENs in C.
      elegans.
AB  - We have developed a method for the generation of conditional knockouts in
      Caenorhabditis elegans by expressing transcription activator-like effector
      nucleases (TALENs) in somatic cells. Using germline transformation with plasmids
      encoding TALENs under the control of an inducible or tissue-specific promoter, we
      observed effective gene modifications and resulting phenotypes in specific
      developmental stages and tissues. We further used this method to bypass the
      embryonic requirement of cor-1, which encodes the homolog of human severe
      combined immunodeficiency (SCID) protein coronin, and we determined its essential
      role in cell migration in larval Q-cell lineages. Our results show that TALENs
      expressed in the somatic cells of model organisms provide a versatile tool for
      functional genomics. 

PMID- 23955275
TI  - Nature-inspired design of motif-specific antibody scaffolds.
AB  - Aberrant changes in post-translational modifications (PTMs) such as phosphate
      groups underlie a majority of human diseases. However, detection and
      quantification of PTMs for diagnostic or biomarker applications often require PTM
      specific monoclonal antibodies (mAbs), which are challenging to generate using
      traditional antibody-selection methods. Here we outline a general strategy for
      producing synthetic, PTM-specific mAbs by engineering a motif-specific 'hot spot'
      into an antibody scaffold. Inspired by a natural phosphate-binding motif, we
      designed and selected mAb scaffolds with hot spots specific for phosphoserine,
      phosphothreonine or phosphotyrosine. Crystal structures of the phospho-specific
      mAbs revealed two distinct modes of phosphoresidue recognition. Our data suggest
      that each hot spot functions independently of the surrounding scaffold, as phage
      display antibody libraries using these scaffolds yielded >50 phospho- and target
      specific mAbs against 70% of target peptides. Our motif-specific scaffold
      strategy may provide a general solution for rapid, robust development of anti-PTM
      mAbs for signaling, diagnostic and therapeutic applications. 

PMID- 23955276
TI  - Surface nucleated growth of dipeptide fibres.
AB  - We report the surface nucleated growth of self-assembled dipeptide films. The
      seeding-layer was a thin dipeptide film with a globular structure. Placing the
      seeding-layer in contact with dipeptide led to growth of fibres overnight. Active
      enzymes were incorporated into the gel by adding them to the growth solution. 

PMID- 23955277
TI  - The impact of hot melt extrusion and spray drying on mechanical properties and
      tableting indices of materials used in pharmaceutical development.
AB  - The impact of melt extrusion (HME) and spray drying (SD) on mechanical properties
      of hypromellose acetate succinate (HPMCAS), copovidone, and their formulated
      blends was studied and compared with that of reference excipients. Tensile
      strength (TS), compression pressure (CP), elastic modulus (E), and dynamic
      hardness (Hd ) were determined along with Hiestand indices using compacts
      prepared at a solid fraction of ~0.85. HPMCAS and copovidone exhibited lower Hd ,
      lower CP, and lower E than the reference excipients and moderate TS. HPMCAS was
      found to be highly brittle based on brittle fracture index values. The CP was 24%
      and 61% higher for HPMCAS after SD and HME, respectively, than for unprocessed
      material along with a higher Hd . Furthermore, the TS of HPMCAS and copovidone
      decreased upon HME. Upon blending melt-extruded HPMCAS with plastic materials
      such as microcrystalline cellulose, the TS increased. These results suggest that
      SD and HME could impact reworkability by reducing deformation of materials and in
      case of HME, likely by increasing density due to heating and shear stress in a
      screw extruder. A somewhat similar effect was observed for the dynamic binding
      index (BId ) of the excipients and formulated blends. Such data can be used to
      quantitate the impact of processing on mechanical properties of materials during
      tablet formulation development.

PMID- 23955278
TI  - Immunohistochemistry reliably detects ALK rearrangements in patients with
      advanced non-small-cell lung cancer.
AB  - Accurate determination of anaplastic lymphoma kinase (ALK) rearrangements is
      critical in identifying ALK-positive patients for targeted therapy in non-small
      cell lung cancer (NSCLC). Fluorescence in situ hybridization (FISH) is the
      current standard method to detect ALK rearrangements but is technically
      challenging and costly. We compared optimised immunohistochemistry (IHC),
      quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in
      situ hybridization techniques in this study of 139 samples of advanced NSCLC with
      non-squamous histology. ALK alteration was found in 32.6 % (43/132) of patients
      by FISH, 32.9 % (45/137) of patients by IHC and 27.9 % (34/122) of samples by qRT
      PCR (concordance rate of 96.9 % between FISH and IHC, 95.7 % between FISH and qRT
      PCR, P < 0.001). IHC sensitivity and specificity were 97.7 % and 96.6 %,
      respectively, while the sensitivity and specificity of qRT-PCR were 89.2 % and
      98.7 %, respectively. ALK rearrangements were more common in young patients (P =
      0.007), non-smokers or light smokers (P = 0.008) and adenocarcinoma histology,
      especially with signet ring cell features (P < 0.001). Optimised IHC could be a
      useful method in screening ALK rearrangements in clinical practice with qRT-PCR
      as an alternative diagnostic tool to clarify specific ALK variants. 

PMID- 23955279
TI  - Schmorl's nodes: current pathophysiological, diagnostic, and therapeutic
      paradigms.
AB  - Schmorl's nodes were first described by the pathologist Christian Schmorl in 1927
      as a herniation of the nucleus pulposus through the cartilaginous and bony
      endplate into the vertebral body. Although such lesions present most commonly as
      incidental findings in asymptomatic patients (or in patients with back or
      radicular pain due to other etiology), there have been several reports
      emphasizing the deleterious effects of the inflammatory response and endplate
      changes elicited by the herniation of for such reasons, Schmorl's nodes have been
      occasionally implicated in the etiology of chronic axial pain as well as in
      pathological osteoporotic fractures. In this article, a thorough literature
      review about the most relevant historical studies on Schmorl's nodes previously
      published is performed. Furthermore, the authors provide an overview about the
      recent advances in basic science research on the pathophysiology of such lesions,
      as well as on current diagnostic and therapeutic paradigms. 

PMID- 23955280
TI  - Infection-enhancing lipopeptides do not improve intranasal immunization of cotton
      rats with a delta-G candidate live-attenuated human respiratory syncytial virus
      vaccine.
AB  - Development of live-attenuated human respiratory syncytial virus (HRSV) vaccines
      has proven to be difficult. Several vaccine candidates were found to be over
      attenuated and displayed limited immunogenicity. Recently, we identified three
      synthetic cationic lipopeptides that enhanced paramyxovirus infections in vitro.
      The infection enhancement proved to be mediated by enhanced virus binding to
      target cells. We hypothesized that these lipopeptides can be used as adjuvants to
      promote immune responses induced by live-attenuated paramyxovirus vaccines. This
      hypothesis was tested in a vaccination and challenge model in cotton rats, using
      a previously described recombinant live-attenuated candidate HRSV vaccine lacking
      the gene encoding the G glycoprotein (rHRSVDeltaG). Surprisingly, intranasal
      vaccination of cotton rats with rHRSVDeltaG formulated in infection-enhancing
      lipopeptides resulted in reduced virus loads in nasopharyngeal lavages, reduced
      seroconversion levels and reduced protection from wild-type HRSV challenge. In
      conclusion, we were unable to demonstrate the feasibility of lipopeptides as
      adjuvants for a candidate live-attenuated HRSV vaccine in the cotton rat model. 

PMID- 23955281
TI  - The influence of spatial variation in chromatin density determined by X-ray
      tomograms on the time to find DNA binding sites.
AB  - In this work, we examine how volume exclusion caused by regions of high chromatin
      density might influence the time required for proteins to find specific DNA
      binding sites. The spatial variation of chromatin density within mouse olfactory
      sensory neurons is determined from soft X-ray tomography reconstructions of five
      nuclei. We show that there is a division of the nuclear space into regions of low
      density euchromatin and high-density heterochromatin. Volume exclusion
      experienced by a diffusing protein caused by this varying density of chromatin is
      modeled by a repulsive potential. The value of the potential at a given point in
      space is chosen to be proportional to the density of chromatin at that location.
      The constant of proportionality, called the volume exclusivity, provides a model
      parameter that determines the strength of volume exclusion. Numerical simulations
      demonstrate that the mean time for a protein to locate a binding site localized
      in euchromatin is minimized for a finite, nonzero volume exclusivity. For binding
      sites in heterochromatin, the mean time is minimized when the volume exclusivity
      is zero (the protein experiences no volume exclusion). An analytical theory is
      developed to explain these results. The theory suggests that for binding sites in
      euchromatin there is an optimal level of volume exclusivity that balances a
      reduction in the volume searched in finding the binding site, with the height of
      effective potential barriers the protein must cross during the search process. 

PMID- 23955282
TI  - Lattice-free models of cell invasion: discrete simulations and travelling waves.
AB  - Invasion waves of cells play an important role in development, disease, and
      repair. Standard discrete models of such processes typically involve simulating
      cell motility, cell proliferation, and cell-to-cell crowding effects in a lattice
      based framework. The continuum-limit description is often given by a reaction
      diffusion equation that is related to the Fisher-Kolmogorov equation. One of the
      limitations of a standard lattice-based approach is that real cells move and
      proliferate in continuous space and are not restricted to a predefined lattice
      structure. We present a lattice-free model of cell motility and proliferation,
      with cell-to-cell crowding effects, and we use the model to replicate invasion
      wave-type behaviour. The continuum-limit description of the discrete model is a
      reaction-diffusion equation with a proliferation term that is different from
      lattice-based models. Comparing lattice-based and lattice-free simulations
      indicates that both models lead to invasion fronts that are similar at the
      leading edge, where the cell density is low. Conversely, the two models make
      different predictions in the high-density region of the domain, well behind the
      leading edge. We analyse the continuum-limit description of the lattice-based and
      lattice-free models to show that both give rise to invasion wave type solutions
      that move with the same speed but have very different shapes. We explore the
      significance of these differences by calibrating the parameters in the standard
      Fisher-Kolmogorov equation using data from the lattice-free model. We conclude
      that estimating parameters using this kind of standard procedure can produce
      misleading results. 

PMID- 23955283
TI  - [C-reactive protein prior to radical cystectomy: preoperative determination of
      CRP].
AB  - BACKGROUND: Numerous studies have shown a positive correlation between elevated C
      reactive protein (CRP) and systemic spread of malignancies. The goal of the
      current study was to assess the predictive significance of preoperative CRP in
      patients undergoing radical cystectomy (RC). MATERIAL AND METHODS: Preoperative
      CRP values were measured in 194 patients undergoing RC because of urothelial
      carcinoma between 1996 and 2005. Elevated CRP level was defined as >= 5 mg/l.
      RESULTS: Preoperative increased CRP values were detected in 89 (45.9%) patients
      and these patients were more likely to have advanced tumor stages (pT3-4),
      positive resection margins and positive lymph nodes. Advanced urinary diversions
      were more common in patients with normal CRP values. In multivariate analysis,
      CRP was identified as an independent prognostic indicator for poor cancer
      specific survival. CONCLUSION: The results confirm previous reports that showed a
      prognostic significance of preoperative CRP elevation.

PMID- 23955284
TI  - Targeting survivin in cancer: novel drug development approaches.
AB  - Survivin is a well-established target in experimental cancer therapy. The
      molecule is over-expressed in most human tumors, but hardly detectable in normal
      tissues. Multiple functions in different subcellular compartments have been
      assigned. It participates in the control of cell division, apoptosis, the
      cellular stress response, and also in the regulation of cell migration and
      metastasis. Survivin expression has been recognized as a biomarker: high
      expression indicates an unfavorable prognosis and resistance to chemotherapeutic
      agents and radiation treatment. Survivin is an unconventional drug target and
      several indirect approaches have been exploited to affect its function and the
      phenotype of survivin-expressing cells. Interference with the expression of the
      survivin gene, the utilization of its messenger RNA, the intracellular
      localization, the interaction with binding partners, the stability of the
      survivin protein, and the induction of survivin-specific immune responses have
      been taken into consideration. A direct strategy to inhibit survivin has been
      based on the identification of a specifically interacting peptide. This peptide
      can recognize survivin intracellularly and cause the degradation of the ligand
      survivin complex. Technology is being developed that might allow the derivation
      of small molecular-weight, drug-like compounds that are functionally equivalent
      to the peptide ligand. 

PMID- 23955285
TI  - Marinopyrrole derivatives as potential antibiotic agents against methicillin
      resistant Staphylococcus aureus (II).
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a major
      problem, causing severe and intractable infections worldwide. MRSA is resistant
      to all beta-lactam antibiotics, and alternative treatments are limited. A very
      limited number of new antibiotics have been discovered over the last half
      century, novel agents for the treatment of MRSA infections are urgently needed.
      Marinopyrrole A was reported to show antibiotic activity against MRSA in 2008.
      After we reported the first total synthesis of (+/-)-marinopyrrole A, we designed
      and synthesized a series of marinopyrrole derivatives. Our structure activity
      relationship (SAR) studies of these novel derivatives against a panel of Gram
      positive pathogens in antibacterial assays have revealed that a para
      trifluoromethyl analog (33) of marinopyrrole A is >= 63-, 8-, and 4-fold more
      potent than vancomycin against methicillin-resistant Staphylococcus epidermidis
      (MRSE), methicillin-susceptible Staphylococcus aureus (MSSA) and MRSA,
      respectively. The results provide valuable information in the search for new
      generation antibiotics.

PMID- 23955286
TI  - Growth and saxitoxin production by Cylindrospermopsis raciborskii (cyanobacteria)
      correlate with water hardness.
AB  - The cosmopolitan and increasing distribution of Cylindrospermopsis raciborskii
      can be attributed to its ecophysiological plasticity and tolerance to changing
      environmental factors in water bodies. In reservoirs in the semi-arid region of
      Brazil, the presence and common dominance of C. raciborskii have been described
      in waters that are considered hard. We investigated the response of a Brazilian
      C. raciborskii strain to water hardness by evaluating its growth and saxitoxin
      production. Based on environmental data, a concentration of 5 mM of different
      carbonate salts was tested. These conditions affected growth either positively
      (MgCO3) or negatively (CaCO3 and Na2CO3). As a control for the addition of
      cations, MgCl2, CaCl2 and NaCl were tested at 5 or 10 mM, and MgCl2 stimulated
      growth, NaCl slowed but sustained growth, and CaCl2 inhibited growth. Most of the
      tested treatments increased the saxitoxin (STX) cell quota after six days of
      exposure. After 12 days, STX production returned to concentrations similar to
      that of the control, indicating an adaptation to the altered water conditions. In
      the short term, cell exposure to most of the tested conditions favored STX
      production over neoSTX production. These results support the noted plasticity of
      C. raciborskii and highlight its potential to thrive in hard waters.
      Additionally, the observed relationship between saxitoxin production and water
      ion concentrations characteristic of the natural environments can be important
      for understanding toxin content variation in other harmful algae that produce
      STX. 

PMID- 23955287
TI  - Feasibility of stress only rubidium-82 PET myocardial perfusion imaging.
AB  - BACKGROUND: Stress only SPECT myocardial perfusion imaging (MPI) is a validated
      strategy to streamline cardiac diagnostic imaging. The potential use of Rb82 PET
      stress only MPI has not been investigated. METHODS AND RESULTS: Stress images
      from 200 Rb82 PET-MPI were reviewed by two blinded readers and categorized as not
      requiring additional rest images (normal) or requiring additional images
      (abnormal or equivocal). No additional images were deemed necessary for 95 (48%)
      and 99 (50%) by the two blinded readers. The stress only interpretation was
      compared to the previous read of the complete rest-stress study. The rate of
      detecting a normal result with stress only reading was 76%-79% with a negative
      predictive value of 94%-95%. Clinical predictors of a normal stress only PET-MPI
      included lower age, the absence of CAD, and female gender, but not body mass
      index. Blinded reads of 50 additional consecutive PET-MPI from patients with
      selected clinical predictors (age <65 years, no known CAD) were then performed.
      Of these, 40 (80%) were normal by previous rest-stress reading, and 34 (68%) were
      categorized as not requiring additional images after stress only reading. PET
      stress only imaging would have resulted in a mean reduction of radiation exposure
      of 2.4 mSv per study according to a published radiation estimate. CONCLUSION:
      Stress only Rb82 PET-MPI is a feasible strategy to reduce resource utilization
      and radiation exposure associated with MPI. This strategy would be most
      applicable to patients with a lower pretest likelihood.

PMID- 23955288
TI  - Veracity and rhetoric in paediatric medicine: a critique of Svoboda and Van
      Howe's response to the AAP policy on infant male circumcision.
AB  - In a recent issue of the Journal of Medical Ethics,Svoboda and Van Howe commented
      on the 2012 changein the American Academy of Pediatrics (AAP) policy on newborn
      male circumcision, in which the AAP stated that benefits of the procedure
      outweigh the risks. Svoboda and Van Howe disagree with the AAP conclusions. We
      show here that their arguments against male circumcision are based on a poor
      understanding of epidemiology,erroneous interpretation of the evidence, selective
      citation of the literature, statistical manipulation of data, and circular
      reasoning. In reality, the scientific evidence indicates that male circumcision,
      especially when performed in the newborn period, is an ethically and medically
      sound low-risk preventive health procedure conferring a lifetime of benefits to
      health and well-being.Policies in support of parent-approved elective newborn
      circumcision should be embraced by the medical,scientific and wider communities.

PMID- 23955289
TI  - Reasons for academic honesty and dishonesty with solutions: a study of pharmacy
      and medical students in New Zealand.
AB  - This paper presents students' views about honest and dishonest actions within the
      pharmacy and medical learning environments. Students also offered their views on
      solutions to ameliorating dishonest action. Three research questions were posed
      in this paper: (1) what reasons would students articulate in reference to
      engaging in dishonest behaviours? (2) What reasons would students articulate in
      reference to maintaining high levels of integrity? (3) What strategies would
      students suggest to decrease engagement in dishonest behaviours and/or promote
      honest behaviours? The design of the study incorporated an initial descriptive
      analysis to interpret students' responses to an 18-item questionnaire about
      justifications for dishonest action. This was followed by a qualitative analysis
      of students' commentaries in reference to why students would engage in either
      honest or dishonest action. Finally a qualitative analysis was conducted on
      students' views regarding solutions to dishonest action. The quantitative results
      showed that students were more likely to use time management and seriousness
      justifications for dishonest actions. The qualitative findings found that
      students' actions (honest or dishonest) were guided by family and friends, the
      need to do well, issues of morality and institutional guidelines. Students
      suggested that dishonest action could be ameliorated by external agencies and
      polarised views between punitive and rewards-based mechanisms were offered. These
      results suggest that these students engaged in dishonest action for various
      reasons and solutions addressing dishonest action need to consider diverse
      mechanisms that likely extend beyond the educational institution. 

PMID- 23955290
TI  - Which indexes are the most important risk factor for cardiorenal events in type 2
      diabetic patients?

PMID- 23955291
TI  - Fragmented QRS predicts cardiovascular death of patients with structural heart
      disease and inducible ventricular tachyarrhythmia.
AB  - BACKGROUND: Fragmented QRS (fQRS) can predict cardiac events, and inducible
      ventricular tachycardia/fibrillation (VT/VF) is a known high-risk factor for
      arrhythmic death. However, whether fQRS is a predictor of cardiac events in
      patients with inducible VT/VF is unknown. We aimed to evaluate whether fQRS is a
      predictor of cardiac events in patients with structural heart disease and
      inducible VT/VF. METHODS AND RESULTS: We retrospectively investigated 98 patients
      with structural heart disease who had a defibrillator device implanted. All
      patients underwent electrophysiological testing prior to or after device
      implantation and VT/VF was induced. fQRS was present in 30 patients. Appropriate
      defibrillator therapies were similar between the fQRS and non-fQRS groups (47%
      vs. 47%). In total, 25 patients (26%) died during a mean follow-up period of 87+/
      43 months. All-cause mortality (12 [40%] vs. 13 [19%]) and cardiovascular deaths
      (9 [30%] vs. 4 [6%]) were significantly higher in the fQRS group than non-fQRS
      group, respectively; Kaplan-Meier analysis revealed significantly lower event
      free survival for all-cause mortality (P=0.012) and cardiovascular deaths
      (P=0.001) for fQRS patients. A multivariable Cox regression model revealed that
      fQRS was an independent predictor of cardiovascular death (hazard ratio, 4.58;
      95% confidence interval, 1.34-15.64; P=0.015). CONCLUSIONS: fQRS is a predictor
      of cardiovascular death in patients with structural heart disease and inducible
      VT/VF.

PMID- 23955293
TI  - Cultural variations in interpretation of postnatal illness: Jinn possession
      amongst Muslim communities.
AB  - Maternal experience of emotional and physical disturbance during the postnatal
      period is a worldwide occurrence but may be interpreted differently according to
      cultural background. Little is known about different expressions and treatment of
      cultural phenomena during the postnatal period such as the affliction of Jinn
      possession in Arabic cultures. Jinn are considered to be evil spirits, which
      cause emotional and physical distress at times of vulnerability such as the
      postnatal period. The aim of this paper was to explore maternal experience of
      Jinn possession and draw parallels with Western interpretations of postnatal
      illness. Ten women in an Arabian Gulf state who had recently given birth and
      identified themselves as having Jinn possession were interviewed as to their
      experiences of Jinn possession. Mothers described the Jinn as evil spirits who
      cause symptoms such as sadness, anxiety and physical malaise during the postnatal
      period. Numerous risk factors for possession emerged such as lack of familial
      support, poverty and a traumatic birth. Clear parallels emerged between Western
      concepts of postnatal illness and Jinn possession. Mothers in Muslim cultures may
      experience Jinn possession during the postnatal period, which reflects similar
      symptoms and aetiology to Western concepts of postnatal illness. With increasing
      multiculturalism in the UK, understanding the origins and perception of Jinn
      possession is important for health professionals working in Muslim communities
      here.

PMID- 23955294
TI  - Application of lipopeptide biosurfactant isolated from a halophile: Bacillus
      tequilensis CH for inhibition of biofilm.
AB  - Biosurfactants are amphiphilic molecules having hydrophobic and hydrophilic
      moieties produced by various microorganisms. These molecules trigger the
      reduction of surface tension or interfacial tension in liquids. A biosurfactant
      producing halophile was isolated from Lake Chilika, a brackish water lake of
      Odisha, India (19 degrees 41'39"N, 85 degrees 18'24"E). The halophile was
      identified as Bacillus tequilensis CH by biochemical tests and 16S rRNA gene
      sequencing and assigned accession no. KC851857 by GenBank. The biosurfactant
      produced by B. tequilensis CH was partially characterized as a lipopeptide using
      thin-layer chromatography, Fourier transform infrared spectroscopy, and nuclear
      magnetic resonance techniques. The minimum effective concentration of a
      biosurfactant for inhibition of pathogenic biofilm (Escherichia coli and
      Streptococcus mutans) on hydrophilic and hydrophobic surfaces was found to be 50
      MUg ml(-1). This finding has potential for a variety of applications. 

PMID- 23955295
TI  - Production of the biopesticide azadirachtin by hairy root cultivation of
      Azadirachta indica in liquid-phase bioreactors.
AB  - Batch cultivation of Azadirachta indica hairy roots was carried out in different
      liquid-phase bioreactor configurations (stirred-tank, bubble column, bubble
      column with polypropylene basket, and polyurethane foam disc as root supports) to
      investigate possible scale-up of the A. indica hairy root culture for in vitro
      production of the biopesticide azadirachtin. The hairy roots failed to grow in
      the conventional bioreactor designs (stirred tank and bubble column). However,
      modified bubble column reactor (with polyurethane foam as root support)
      configuration facilitated high-density culture of A. indica hairy roots with a
      biomass production of 9.2 g l(-1)dry weight and azadirachtin yield of 3.2 mg g(
      1) leading to a volumetric productivity of azadirachtin as 1.14 mg l(-1) day(-1).
      The antifeedant activity in the hairy roots was also evaluated by no choice
      feeding tests with known concentrations of the hairy root powder and its solvent
      extract separately on the desert locust Schistocerca gregaria. The hairy root
      powder and its solvent extract demonstrated a high level of antifeedant activity
      (with an antifeedant index of 97 % at a concentration of 2 % w/v and 83 % at a
      concentration of 0.05 % (w/v), respectively, in ethanol). 

PMID- 23955296
TI  - Effects of nitrogen composition on fermentation performance of brewer's yeast and
      the absorption of peptides with different molecular weights.
AB  - Four kinds of worts with different nitrogen compositions were used to examine
      their effects on fermentation performance of brewer's yeast. The absorption
      pattern of peptides with different molecular weights (Mw) in yeast cells during
      wort fermentation was also investigated. Results showed that both the nitrogen
      composition and level had significant impacts on the yeast biomass accumulation,
      ethanol production, and free amino nitrogen and sugars consumption rates. Worts
      supplemented with wheat gluten hydrolysates increased 11.5% of the biomass, 5.9%
      of fermentability, and 0.6% of ethanol content and decreased 25.6% of residual
      sugar content during wort fermentation. Moreover, yeast cells assimilated
      peptides with various Mw differently during fermentation. Peptides with Mw below
      1 kDa decreased quickly, and the rate of assimilation was more than 50% at the
      end of fermentation, while those with Mw above 10 kDa almost could not be
      assimilated by yeast. All these results further indicated that the level and
      composition of wort nitrogen had significant impacts on the growth and
      fermentation performances of brewer's yeast, and peptides with Mw below 1 kDa
      were one of preferred nitrogen sources for brewer's yeast. 

PMID- 23955297
TI  - Improvement of strain Penicillium sp. EZ-ZH190 for tannase production by induced
      mutation.
AB  - In the search for an efficient producer of tannase, Penicillium sp. EZ-ZH190 was
      subjected to mutagenesis using heat treatment and strain EZ-ZH290 was isolated.
      The maximum tannase in this mutant strain was 4.32 U/mL with an incubation period
      of 84 h as compared to wild strain EZ-ZH190 where the incubation period was 96 h
      with a maximum enzyme activity of 4.33 U/mL. Also, the Penicillium sp. EZ-ZH290
      tannase had a maximum activity at 40  degrees C and pH 5.5. Then, the spores of
      strain EZ-ZH290 were subjected to gamma irradiation mutagenesis and strain EZ
      ZH390 was isolated. Strain EZ-ZH390 exhibited higher tannase activity (7.66 U/mL)
      than the parent strain EZ-ZH290. It was also found that Penicillium sp. EZ-ZH390
      tannase had an optimum activity at 35  degrees C and a broad pH profile with an
      optimum at pH 5.5. The tannase pH stability of Penicillium sp. EZ-ZH390 and its
      maximum production of tannase followed the same trend for five generations
      confirming the occurrence of stable mutant. This paper is shown that gamma
      irradiation can mutate the Penicillium sp. leading to increase the tannase
      production. 

PMID- 23955299
TI  - Template-directed self-assembly by way of molecular recognition at the micellar
      solvent interface: modulation of the critical micelle concentration.
AB  - By incorporating the concepts of structural preorganisation and complementarity
      in concert with non-covalent donor-acceptor [pipi] and hydrophobic interactions,
      a duo of pi-electron deficient bipyridinium-based linear and gemini amphiphiles
      capable of responding to molecular templation have been designed and synthesised.
      When combined with pi-electron rich di(ethylene glycol)-disubstituted 1,5
      dihydroxynaphthalene, a dramatic decrease in the critical aggregation
      concentration by ~66% was observed with concomitant increases in the hydrodynamic
      diameter, zeta-potential, and Langmuir surface pressures of the micellar
      solutions-thus enhancing the detergents' efficiency and effectiveness at lowering
      the surface tension of water. By employing a phase separation model that takes
      into account the degree of counterion binding to the micellar aggregate
      superstructure, the effects of donor-acceptor templation on the Gibb's free
      energy of micellisation (DeltaG) for the amphiphiles was quantified. It was found
      that donor-acceptor templation was capable of lowering DeltaG by up to 1.75 kcal
      mol(-1) at which point it was observed, while under the influence of molecular
      templation, that linear single hydrophobic tailed detergent molecules exhibit
      properties characteristic of double-tailed phospholipid-like gemini surfactants. 

PMID- 23955298
TI  - Familial megacystis microcolon intestinal hypoperistalsis syndrome: a systematic
      review.
AB  - BACKGROUND: Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is
      a rare and severe disorder of functional obstruction affecting bladder and bowel,
      usually diagnosed in the neonatal period. Over 230 cases have been reported since
      Berdon and colleagues first described this clinical entity in 1976. The exact
      pathogenesis of MMIHS is unknown. Familial occurrence of MMIHS has been reported
      and could offer insight into the aetiology of this disease. The purpose of this
      study was to systematically review the published literature for the evidence of
      familial MMIHS and to characterise these presentations. METHODS: A literature
      search was performed using the keywords "megacystis microcolon intestinal
      hypoperistalsis" (1976-2013). Retrieved articles, including additional studies
      from reference lists, were reviewed for consanguinity between parents and
      recurrence of MMIHS between siblings. Data were extracted for cases where
      familial MMIHS was present. RESULTS: A total of 47 patients were reported in
      which familial MMIHS was likely or confirmed. 15 sibling sets were definitively
      diagnosed with MMIHS (14 pairs and one set of three siblings). Four further index
      patients with a confirmed diagnosis and also one of the sibling pairs were
      reported to have a sibling in which MMIHS was probable. Consanguinity between
      parents was present in four of the confirmed sibling sets and in an additional
      seven individual cases. The outcome for familial MMIHS is generally poor.
      Multiple sibling fatalities were frequent and in only one family were both
      siblings' survivors at the time of reporting. CONCLUSION: Consanguinity between
      parents and recurrence in siblings indicate that MMIHS is inherited in an
      autosomal recessive manner. With the advent of next generation sequencing, these
      familial clusters may be key to determining the genetic basis for MMIHS.

PMID- 23955300
TI  - Limitations of routine neuroimaging in predicting outcomes of preterm infants.
AB  - INTRODUCTION: Preterm births are increasing in number and while the rates of
      cerebral palsy have declined, there are increasing numbers of infants who survive
      with handicaps. In some studies, up to 50 % of children will have morbidity when
      followed up to school age. METHODS: A review of current literature was conducted
      to determine the validity of routine cranial ultrasound scans (CUS) to predict
      neurodevelopmental outcomes, including motor and cognitive deficits. We also
      reviewed the additional benefit offered by including MRI scans in scanning
      protocols to enhance the reliability in predicting the neurodevelopmental
      sequelae of prematurity. RESULTS: CUS is valuable as a screening tool to
      determine significant brain injury when conducted regularly over the first weeks
      of life in preterm infants. Subtle changes on CUS are difficult to interpret and
      more precise information is offered by performing MRI scans. These are most often
      carried out at term equivalent age but earlier scans may be just as useful in
      predicting neurocognitive outcomes. When MRI scans are either normal or seriously
      abnormal, there is a very clear correlation with outcome to 2 years of age. Mild
      and moderate degrees of injury defined on MRI need more sophisticated scanning
      sequences to determine the likelihood of associated sequelae. Follow-up to school
      age is essential to diagnose more subtle cognitive delays. CONCLUSION: CUS
      provides a good screening tool to detect serious brain injury resulting in motor
      handicaps but MRI scans are complementary and necessary to accurately predict the
      outcomes of preterm infants, especially cognitive delays.

PMID- 23955301
TI  - Kinetochore kinesin CENP-E is a processive bi-directional tracker of dynamic
      microtubule tips.
AB  - During vertebrate mitosis, the centromere-associated kinesin CENP-E (centromere
      protein E) transports misaligned chromosomes to the plus ends of spindle
      microtubules. Subsequently, the kinetochores that form at the centromeres
      establish stable associations with microtubule ends, which assemble and
      disassemble dynamically. Here we provide evidence that after chromosomes have
      congressed and bi-oriented, the CENP-E motor continues to play an active role at
      kinetochores, enhancing their links with dynamic microtubule ends. Using a
      combination of single-molecule approaches and laser trapping in vitro, we
      demonstrate that once reaching microtubule ends, CENP-E converts from a lateral
      transporter into a microtubule tip-tracker that maintains association with both
      assembling and disassembling microtubule tips. Computational modelling of this
      behaviour supports our proposal that CENP-E tip-tracks bi-directionally through a
      tethered motor mechanism, which relies on both the motor and tail domains of CENP
      E. Our results provide a molecular framework for the contribution of CENP-E to
      the stability of attachments between kinetochores and dynamic microtubule ends. 

PMID- 23955303
TI  - Riquiqui and minibrain are regulators of the hippo pathway downstream of
      Dachsous.
AB  - The atypical cadherins Fat (Ft) and Dachsous (Ds) control tissue growth through
      the Salvador-Warts-Hippo (SWH) pathway, and also regulate planar cell polarity
      and morphogenesis. Ft and Ds engage in reciprocal signalling as both proteins can
      serve as receptor and ligand for each other. The intracellular domains (ICDs) of
      Ft and Ds regulate the activity of the key SWH pathway transcriptional co
      activator protein Yorkie (Yki). Signalling from the FtICD is well characterized
      and controls tissue growth by regulating the abundance of the Yki-repressive
      kinase Warts (Wts). Here we identify two regulators of the Drosophila
      melanogaster SWH pathway that function downstream of the DsICD: the WD40 repeat
      protein Riquiqui (Riq) and the DYRK-family kinase Minibrain (Mnb). Ds physically
      interacts with Riq, which binds to both Mnb and Wts. Riq and Mnb promote Yki
      dependent tissue growth by stimulating phosphorylation-dependent inhibition of
      Wts. Thus, we describe a previously unknown branch of the SWH pathway that
      controls tissue growth downstream of Ds. 

PMID- 23955302
TI  - A tuberous sclerosis complex signalling node at the peroxisome regulates mTORC1
      and autophagy in response to ROS.
AB  - Subcellular localization is emerging as an important mechanism for mTORC1
      regulation. We report that the tuberous sclerosis complex (TSC) signalling node,
      TSC1, TSC2 and Rheb, localizes to peroxisomes, where it regulates mTORC1 in
      response to reactive oxygen species (ROS). TSC1 and TSC2 were bound by
      peroxisomal biogenesis factors 19 and 5 (PEX19 and PEX5), respectively, and
      peroxisome-localized TSC functioned as a Rheb GTPase-activating protein (GAP) to
      suppress mTORC1 and induce autophagy. Naturally occurring pathogenic mutations in
      TSC2 decreased PEX5 binding, and abrogated peroxisome localization, Rheb GAP
      activity and suppression of mTORC1 by ROS. Cells lacking peroxisomes were
      deficient in mTORC1 repression by ROS, and peroxisome-localization-deficient TSC2
      mutants caused polarity defects and formation of multiple axons in neurons. These
      data identify a role for the TSC in responding to ROS at the peroxisome, and
      identify the peroxisome as a signalling organelle involved in regulation of
      mTORC1. 

PMID- 23955304
TI  - Two mixed-NH3/amine platinum (II) anticancer complexes featuring a
      dichloroacetate moiety in the leaving group.
AB  - Two mixed-NH3/amine platinum (II) complexes of 3-dichoroacetoxylcyclobutane-1, 1
      dicarboxylate have been prepared in the present study and characterized by
      elemental analysis and IR, HPLC-MS and (1)H, (13)C-NMR. The complexes exist in
      equilibrium between two position isomeric forms and undergo hydrolysis reaction
      in aqueous solution, releasing the platinum pharmacophores and dichloroacetate
      which is a small-molecular cell apoptosis inducer. Both complexes were evaluated
      for in vitro cytotoxic profile in A549, SGC-7901 and SK-OV-3 cancer cells as well
      as in BEAS-2B normal cells. They exhibit markedly cytotoxicity toward cancer
      cells by selectively inducing the apoptosis of cancer cells, whereas leaving
      normal cells less affected. They have also the ability to overcome the resistance
      of SK-OV-3 cancer cells to cisplatin. Our findings offer an alternative novel way
      to develop platinum drugs which can both overcome the drug resistance and
      selectively target tumor cells.

PMID- 23955305
TI  - Effect of vasopressin on the expression of genes for key enzymes of hyaluronan
      turnover in Wistar Albino Glaxo and Brattleboro rat kidneys.
AB  - Hyaluronan (HA), the major glycosaminoglycan of the interstitial matrix, is
      heterogeneously distributed within the kidney. Using real-time RT-PCR, we tested
      the assumption that renal HA may be involved in the long-term effect of
      vasopressin on water reabsorption. The expression of the genes encoding
      hyaluronan synthase-2 (Has2), hyaluronidase-1 and hyaluronidase-2 (Hyal1 and
      Hyal2) was studied in the kidneys of Wistar Albino Glaxo (WAG) and homozygous
      vasopressin-deficient Brattleboro rats treated with the V2 receptor-selective
      vasopressin analogue dDAVP (100 MUg (kg body wt)(-1), i.p., twice a day for 2
      days). The Has2 mRNA content was the highest in the kidney papilla of the
      hydrated WAG and control Brattleboro rats, devoid of vasopressin. In WAG rats,
      dDAVP induced a considerable decrease in Has2 mRNA content in the papilla, with
      less pronounced changes in the cortex. The changes elicited by dDAVP in
      Brattleboro rats tended to be the same as in WAG rats, but weaker. In contrast to
      Has2, dDAVP treatment caused a significant increase in the Hyal1 and Hyal2 mRNA
      content in the renal papilla of WAG and Brattleboro rats. In rats of both
      strains, there was a good fit between Hyal1 and Hyal2 transcriptional levels and
      changes in hyaluronidase activity in the renal tissue. It is suggested that
      vasopressin is able to inhibit the synthesis of HA and concomitantly promote its
      degradation in the interstitium of the renal papilla, thereby facilitating water
      flow between elements of the renal countercurrent system. The implications for
      this effect are discussed in the context of the data in the literature. 

PMID- 23955306
TI  - Admittance-based pressure-volume loop measurements in a porcine model of chronic
      myocardial infarction.
AB  - The aim of this study was to validate admittance-based pressure-volume (PV) loop
      measurements for the assessment of cardiac function in a porcine model of chronic
      myocardial infarction. The traditional PV loop measurement technique requires
      hypertonic saline injections for parallel conductance correction prior to signal
      conversion into volume. Furthermore, it assumes a linear relationship between
      conductance and volume. More recently, an admittance-based technique has been
      developed, which continuously measures parallel conductance and uses a non-linear
      equation for volume calculation. This technique has not yet been evaluated in a
      large-animal model of myocardial ischaemia. Eleven pigs underwent invasive PV
      measurements with the admittance system (AS) and the traditional conductance
      system followed by three-dimensional echocardiography (3DE). After baseline
      measurements, pigs were subjected to 90 min left anterior descending coronary
      artery occlusion, followed by the same measurements at 8 weeks follow-up. In the
      healthy heart, the AS showed good agreement with 3DE for left ventricular volumes
      and a reasonable correlation for ejection fraction (r = 0.756, P = 0.007). At
      follow-up, an increase in end-systolic volume was observed with 3DE (+15.4 +/-
      14.4 ml, P = 0.005) and the AS (+34.6 +/- 36.1 ml, P = 0.010). The ejection
      fraction measured with 3DE (-13.2 +/- 5.2%, P < 0.001) and the AS (-20.3 +/-
      11.2%, P < 0.001) significantly decreased. We conclude that the AS can be used
      for quantitative monitoring of changes in cardiac function induced by myocardial
      infarction and provides comparable results to 3DE, rendering it a useful tool for
      functional testing in large-animal cardiac models. 

PMID- 23955307
TI  - Genetic dissection of puberty in mice.
AB  - Determining the neural mechanisms controlling gonadotrophin-releasing hormone
      (GnRH) release is of pivotal importance in understanding central control of
      reproductive physiology in vertebrates. Targeted genetic manipulation of
      kisspeptin and GPR54 neurons has provided new insights into the mechanisms
      modulating GnRH release and thereby regulating hypothalamic-pituitary-gonadal
      axis activity during reproductive maturation. While conditional ablation of the
      oestrogen receptor alpha gene in kisspeptin neurons results in a dramatic
      advancement of the onset of puberty in female mice, subsequent pubertal
      maturation is arrested in these animals, as they fail to acquire normal ovulatory
      cyclicity. These data suggest that two oestrogen receptor alpha-dependent
      mechanisms, one a 'brake' and the other an 'accelerator', are sequentially
      operated in kisspeptin neurons during pubertal development of female mice to gate
      and then to activate GnRH release. In a different experimental approach, we
      removed entire kisspeptin neurons from the mouse brain and thus from the neural
      circuits controlling reproduction. Surprisingly, the onset of puberty in females
      was unaffected by kisspeptin neuron ablation. Furthermore, the animals attained
      regular ovulatory cyclicity and were fertile. Consistent with this, female mice
      lacking neurons that express the kisspeptin receptor GPR54 were also fertile,
      suggesting female reproductive maturation in the absence of kisspeptin/GPR54
      signalling. However, acute kisspeptin neuron ablation in adult mice inhibited
      fertility, indicating that there is developmental compensation for the loss of
      kisspeptin neurons during reproductive neural circuit formation. Finally, we
      showed that kisspeptin neurons become an indispensable part of reproductive
      neural circuitry in the mouse brain before postnatal day 20. 

PMID- 23955308
TI  - Use of genetic models of idiopathic hypogonadotrophic hypogonadism in mice and
      men to understand the mechanisms of disease.
AB  - Mutations in the genes encoding the neuropeptides kisspeptin and neurokinin B, as
      well as their receptors, are associated with gonadotrophin-releasing hormone
      (GnRH) deficiency and a failure to initiate and/or progress through puberty.
      Although the total number of patients studied to date is small, mutations in the
      kisspeptin pathway appear to result in lifelong GnRH deficiency. Mice with
      mutations in kisspeptin and the kisspeptin receptor, Kiss1(-/-) and Kiss1r(-/-),
      respectively, appear to be phenocopies of the human with abnormal sexual
      maturation and infertility. In contrast, mutations in the neurokinin B pathway
      lead to a more variable adult reproductive phenotype, with a subset of
      hypogonadotrophic individuals demonstrating paradoxical recovery of reproductive
      function later in life. While 'reversal' remains poorly understood, the ability
      to recover reproductive function indicates that neurokinin B may play different
      roles in the initiation of sexual maturation compared with the maintenance of
      adult reproductive function. Mice with mutations in the gene encoding the
      neurokinin B receptor, Tacr3, have abnormal oestrous cycles and subfertility but,
      similar to their human counterparts, appear less severely affected than mice with
      kisspeptin deficiency. Further investigations into the interaction between the
      kisspeptin and neurokinin B pathways will reveal key insights into how GnRH
      neuronal modulation occurs at puberty and throughout reproductive life. 

PMID- 23955309
TI  - Modulation of food intake by mTOR signalling in the dorsal motor nucleus of the
      vagus in male rats: focus on ghrelin and nesfatin-1.
AB  - Previous studies have demonstrated that mammalian target of rapamycin (mTOR)
      signalling in the hypothalamus is involved in the control of energy homeostasis.
      The aim of this study was to characterize the effect of mTOR signalling in the
      dorsal motor nucleus of the vagus (DMNV) on energy intake. Phospho-mTOR was
      detected in the DMNV neurons, and its levels were increased by energy
      deprivation. Rapamycin significantly inhibited mTOR activity and reduced food
      intake when administrated into the fourth ventricle. Exposure of DMNV neurons to
      ghrelin increased the phosphorylation of mTOR. Injection of ghrelin into the
      fourth ventricle significantly increased food intake relative to the control
      vehicle. Pretreatment with rapamycin for 15 min attenuated the orexigenic effect
      of ghrelin. A reduction in the phosphorylation of mTOR was observed following
      injection of nesfatin-1 into the fourth ventricle. When administrated by
      injection into the fourth ventricle, nesfatin-1 suppressed food intake in
      comparison with the control vehicle. The anorexigenic effect of nesfatin-1 was
      significantly attenuated by pretreatment with leucine for 15 min. All these
      findings suggest that mTOR signalling in the DMNV neurons regulates both the
      nutrient and the hormonal signals for the modulation of food intake. 

PMID- 23955310
TI  - Physiology of invertebrate oxytocin and vasopressin neuropeptides.
AB  - Neuropeptides and regulatory peptide hormones control many developmental,
      physiological and behavioural processes in animals, including humans. The
      nonapeptides oxytocin and arginine vasopressin are produced and released by the
      pituitary gland and have actions on many organs and tissues. Receptive cells
      possess particular receptors to which the peptides bind as ligands, leading to
      activation of G-protein-coupled receptors, hence cellular responses. In humans
      and other mammalian species, oxytocin and vasopressin mediate a range of
      peripheral and central physiological functions that are important for
      osmoregulation, reproduction, complex social behaviours, memory and learning. The
      origin of the oxytocin/vasopressin signalling system is thought to date back more
      than 600 million years. All vertebrate oxytocin- and vasopressin-like peptides
      have presumably evolved from the ancestral nonapeptide vasotocin by gene
      duplication and today are present in vertebrates, including mammals, birds,
      reptiles, amphibians and fish. Oxytocin- and vasopressin-like peptides have been
      identified in several invertebrate species, including molluscs, annelids,
      nematodes and arthropods. Members of this peptide family share high sequence
      similarity, and it is possible that they are functionally related across the
      entire animal kingdom. However, it is evident that not all animals express
      oxytocin/vasopressin neuropeptides and that there is little information available
      about the biology and physiology of this signalling system of invertebrates and,
      in particular, of insects, which represent more than half of all known living
      organisms. This report describes the discovery of novel oxytocin- and vasopressin
      like peptides in arthropods and summarizes the status quo of the functional
      relevance of this neuropeptide signalling system in invertebrates, which will
      have beneficial implications for the design of selective and potent ligands to
      human oxytocin and vasopressin receptors. 

PMID- 23955311
TI  - The neural regulation of the kidney in hypertension and renal failure.
AB  - NEW FINDINGS: What is the topic of this review? Reports that bilateral renal
      denervation in resistant hypertensive patients results in a long-lasting
      reduction in blood pressure raise the question of the underlying mechanisms
      involved and how they may be deranged in pathophysiological states of
      hypertension and renal failure. What advances does it highlight? The renal
      sensory afferent nerves and efferent sympathetic nerves work together to exert an
      important control over extracellular fluid volume, hence the level at which blood
      pressure is set. This article emphasizes that both the afferent and the efferent
      renal innervation may contribute to the neural dysregulation of the kidney that
      occurs in chronic renal disease and resistant hypertension. Autonomic control is
      central to cardiovascular homeostasis, and this is exerted not only at the level
      of the heart and blood vessels but also at the kidney. At the kidney, the
      sympathetic neural regulation of renin release and fluid reabsorption may
      influence fluid balance and, in the longer term, the level at which blood
      pressure is set. The role of the renal innervation in the regulation of blood
      pressure has received renewed attention over the past few years, following the
      reports that bilateral renal denervation of resistant hypertensive patients
      resulted in a marked reduction in blood pressure, which has been maintained for
      several years. Such has been the interest that this approach of renal denervation
      is being applied in other patient groups with diabetes, obesity and renal
      failure, with the hope that there may be a sustained reduction in blood pressure
      as well as the amelioration of some aspects of the metabolic syndrome. However,
      the factors that come into play to cause the rise in blood pressure in these
      patient groups, particularly the resistant hypertensive patients, are far from
      clear. Moreover, the mechanisms leading to the fall in blood pressure following
      renal denervation of resistant hypertensive patients currently elude our
      understanding and is therefore an area that requires much more investigation to
      enhance our insight.

PMID- 23955312
TI  - Parametric and cadaveric models of lumbar flexion instability and flexion
      restricting dynamic stabilization system.
AB  - PURPOSE: Development of a dynamic stabilization system often involves costly and
      time-consuming design iterations, testing and computational modeling. The aims of
      this study were (1) develop a simple parametric model of lumbar flexion
      instability and use this model to identify the appropriate stiffness of a flexion
      restricting stabilization system (FRSS), and (2) in a cadaveric experiment,
      validate the predictive value of the parametric model. METHODS: Literature was
      surveyed for typical parameters of intact and destabilized spines: stiffness in
      the high flexibility zone (HFZ) and high stiffness zone, and size of the HFZ.
      These values were used to construct a bilinear parametric model of flexion
      kinematics of intact and destabilized lumbar spines. FRSS implantation was
      modeled by iteratively superimposing constant flexion stiffnesses onto the
      parametric model. Five cadaveric lumbar spines were tested intact; after L4-L5
      destabilization (nucleotomy, midline decompression); and after FRSS implantation.
      Specimens were loaded in flexion/extension (8 Nm/6 Nm) with 400 N follower load
      to characterize kinematics for comparison with the parametric model. RESULTS: To
      accomplish the goal of reducing ROM to intact levels and increasing stiffness to
      approximately 50 % greater than intact levels, flexion stiffness contributed by
      the FRSS was determined to be 0.5 Nm/deg using the parametric model. In
      biomechanical testing, the FRSS restored ROM of the destabilized segment from 146
      +/- 13 to 105 +/- 21 % of intact, and stiffness in the HFZ from 41 +/- 7 to 135
      +/- 38 % of intact. CONCLUSIONS: Testing demonstrated excellent predictive value
      of the parametric model, and that the FRSS attained the desired biomechanical
      performance developed with the model. A simple parametric model may allow
      efficient optimization of kinematic design parameters.

PMID- 23955315
TI  - Coherent manipulation of spin qubits based on polyoxometalates: the case of the
      single ion magnet [GdW30P5O110]14-.
AB  - Polyoxometalate single ion magnet [GdW30P5O110](14-) (1) has been studied by
      generalized Rabi oscillation experiments. It was possible to increase the number
      of coherent rotations tenfold through matching the Rabi frequency with the
      frequency of the proton. Achieving high coherence with polyoxometalate chemistry,
      we show its excellent potential not only for the storage of quantum information
      but even for the realization of quantum algorithms.

PMID- 23955314
TI  - Quantitative trait loci of stripe rust resistance in wheat.
AB  - Over thirty publications during the last 10 years have identified more than 140
      QTLs for stripe rust resistance in wheat. It is likely that many of these QTLs
      are identical genes that have been spread through plant breeding into diverse
      backgrounds through phenotypic selection under stripe rust epidemics. Allelism
      testing can be used to differentiate genes in similar locations but in different
      genetic backgrounds; however, this is problematic for QTL studies where multiple
      loci segregate from any one parent. This review utilizes consensus maps to
      illustrate important genomic regions that have had effects against stripe rust in
      wheat, and although this methodology cannot distinguish alleles from closely
      linked genes, it does highlight the extent of genetic diversity for this trait
      and identifies the most valuable loci and the parents possessing them for
      utilization in breeding programs. With the advent of cheaper, high throughput
      genotyping technologies, it is envisioned that there will be many more
      publications in the near future describing ever more QTLs. This review sets the
      scene for the coming influx of data and will quickly enable researchers to
      identify new loci in their given populations.

PMID- 23955313
TI  - Gray-matter macrostructure in cognitively healthy older persons: associations
      with age and cognition.
AB  - A deeper understanding of brain macrostructure and its associations with
      cognition in persons who are considered cognitively healthy is critical to the
      early detection of persons at risk of developing dementia. Few studies have
      examined the associations of all three gray-matter macrostructural brain indices
      (volume, thickness, surface area) with age and cognition, in the same persons who
      are over the age of 65 and do not have cognitive impairment. We performed
      automated morphometric reconstruction of total gray matter, cortical gray matter,
      subcortical gray matter and 84 individual regions in 186 persons (60 % over the
      age of 80) without cognitive impairment. Morphometric measures were scaled and
      expressed as difference per decade of age and an adjusted score was created to
      identify those regions in which there was greater atrophy per decade of age
      compared to cortical or subcortical brain averages. The results showed that there
      is substantial total volume loss and cortical thinning in cognitively healthy
      older persons. Thinning was more widespread than volume loss, but volume loss,
      particularly in temporoparietal and hippocampal regions, was more strongly
      associated with cognition. 

PMID- 23955316
TI  - Effect of lipophilicity on microneedle-mediated iontophoretic transdermal
      delivery across human skin in vitro.
AB  - The effect of lipophilicity of drug on the microneedle (MN)-mediated
      iontophoretic delivery across dermatomed human skin was studied. Beta blockers
      with similar pKa but varied log P values were selected as model drugs in this
      study. Iontophoresis (ITP) or MNs, when used independently, increased the
      transdermal flux of beta blockers as compared with passive delivery (PD). ITP
      across the MN-treated skin (MN + ITP) increased the permeation rate of all beta
      blockers as compared with PD (p < 0.001). The enhancement ratios (ER) for
      hydrophilic molecules (atenolol and sotalol) were 71- and 78-fold higher for ITP
      + MN as compared with PD. However, for lipophilic molecule such as propranolol,
      there was 10-fold increase in the ER as compared with PD. These observations were
      further substantiated by the skin retention data; an inverse relationship between
      the skin retention and the hydrophilicity of the drug was observed. The results
      in the present study point out that the lipophilicity of the molecule plays a
      significant role on the electrically assisted transdermal delivery of drugs
      across the microporated skin. Using the combination of ITP + MN, hydrophilic
      drugs (atenolol and sotalol) were delivered at a much higher rate as compared
      with lipophilic molecules (propranolol and acebutolol).

PMID- 23955317
TI  - Computer-assisted solid lung nodule 3D volumetry on CT: influence of scan mode
      and iterative reconstruction: a CT phantom study.
AB  - OBJECTIVE: To evaluate the effect of high-resolution scan mode and iterative
      reconstruction on lung nodule 3D volumetry. METHODS: Solid nodules with various
      sizes (5, 8, 10 and 12 mm) were placed inside a chest phantom. CT images were
      obtained with various tube currents, scan modes (conventional mode, high
      resolution mode) and iterative reconstructions [0, 50 and 100 % blending of
      adaptive statistical iterative reconstruction (ASiR) and filtered back
      projection]. The nodule volumes were calculated using semiautomatic software and
      compared with the assumed volume from the nodules. RESULTS: The mean absolute and
      relative percentage error improved when using iterative reconstruction especially
      when using the conventional scan mode; however, this effect was not significant.
      Significant reduction in volume overestimation was observed when using high
      resolution scan mode (P = 0.011). CONCLUSION: The high-resolution mode
      significantly reduces the volume overestimation of 3D volumetry. Iterative
      reconstruction shows a reduction in volume overestimation and error margin
      especially with the conventional scan mode; however, this effect was not
      significant.

PMID- 23955318
TI  - Psychometric characteristics of the Drug Use Disorders Identification Test
      (DUDIT) and the Drug Use Disorders Identification Test-Extended (DUDIT-E) among
      young drug users in Hungary.
AB  - BACKGROUND: The Drug Use Disorders Identification Test (DUDIT) was developed for
      problematic substance use screening, and for a more detailed assessment of
      problematic use, the Drug Use Disorders Identification Test-Extended (DUDIT-E)
      was additionally developed. PURPOSE: Examining the psychometric properties of
      DUDIT and DUIT-E across diverse settings in populations of young drug users.
      METHODS: We examined the psychometric characteristics of these instruments across
      various settings in populations of young substance users differing in substance
      use severity and treatment status. Data were collected from three clinically
      relevant groups (n = 259) as well as a control sample of college students (n =
      109). RESULTS: Reliability analyses indicated good internal consistency for both
      instruments; high intraclass correlations further indicated good test-retest
      reliability. Differences among study groups were significant on the DUDIT scale
      and all DUDIT-E subscales (p < 0.01), with the target groups exhibiting higher
      scores compared to controls. A two-factor solution was identified for the factor
      structure of DUDIT. CONCLUSION: The Hungarian version of DUDIT and DUDIT-E can
      effectively identify substance use problems among young users.

PMID- 23955319
TI  - Advances in the study of HLA-restricted epitope vaccines.
AB  - Vaccination is a proven strategy for protection from disease. An ideal vaccine
      would include antigens that elicit a safe and effective protective immune
      response. HLA-restricted epitope vaccines, which include T-lymphocyte epitopes
      restricted by HLA alleles, represent a new and promising immunization approach.
      In recent years, research in HLA-restricted epitope vaccines for the treatment of
      tumors and for the prevention of viral, bacterial, and parasite-induced
      infectious diseases have achieved substantial progress. Approaches for the
      improvement of the immunogenicity of epitope vaccines include (1) improving the
      accuracy of the methods used for the prediction of epitopes, (2) making use of
      additional HLA-restricted CD8(+) T-cell epitopes, (3) the inclusion of specific
      CD4(+) T-cell epitopes, (4) adding B-cell epitopes to the vaccine construction,
      (5) finding more effective adjuvants and delivery systems, (6) using immunogenic
      carrier proteins, and (7) using multiple proteins as epitopes sources. In this
      manuscript, we review recent research into HLA-restricted epitope vaccines. 

PMID- 23955321
TI  - Characterization of nucleosides and nucleobases in natural Cordyceps by HILIC
      ESI/TOF/MS and HILIC-ESI/MS.
AB  - A method combining hydrophilic interaction chromatography (HILIC) and
      electrospray ionization mass spectrometry (ESI-MS) was developed for the
      characterization and determination of natural Cordyceps. Separation was achieved
      on a Waters Xbridge Amide column with gradient elution. Identification of 15
      target nucleosides and nucleobases was based on retention time, UV spectra and
      mass measurements of the protonated molecules ([M+H]+) and main fragment ions
      (ESI-TOF/MS). Eight non-target compounds were tentatively identified by ESI
      TOF/MS. The 15 target compounds were quantified by HILIC-ESI-MS/MS using time
      programmed selective ion monitoring or multiple reaction monitoring in positive
      ion mode under optimized mass conditions. This technique showed good linearity,
      repeatability and recovery. This approach was also successfully implemented in
      the analysis of nucleosides and nucleobases in 12 batches of natural Cordyceps
      samples that were collected from different regions in China. The developed HILIC
      ESI-MS method exhibited clear advantages in identifying and determining highly
      polar bioactive components in Cordyceps, as well as their quality control.

PMID- 23955322
TI  - Antidiabetic and antioxidant properties of alkaloids from Catharanthus roseus
      (L.) G. Don.
AB  - Catharanthus roseus (L.) G. Don is a herbal plant traditionally used by local
      populations in India, South Africa, China and Malaysia to treat diabetes. The
      present study reports the in vitro antioxidant and antidiabetic activities of the
      major alkaloids isolated from Catharanthus roseus (L.) G. Don leaves extract.
      Four alkaloids--vindoline I, vindolidine II, vindolicine III and vindolinine IV-
      were isolated and identified from the dichloromethane extract (DE) of this
      plant's leaves. DE and compounds I-III were not cytotoxic towards pancreatic beta
      TC6 cells at the highest dosage tested (25.0 ug/mL). All four alkaloids induced
      relatively high glucose uptake in pancreatic beta-TC6 or myoblast C2C12 cells,
      with III showing the highest activity. In addition, compounds II-IV demonstrated
      good protein tyrosine phosphatase-1B (PTP-1B) inhibition activity, implying their
      therapeutic potential against type 2 diabetes. III showed the highest antioxidant
      potential in ORAC and DPPH assays and it also alleviated H2O2-induced oxidative
      damage in beta-TC6 cells at 12.5 ug/mL and 25.0 ug/mL.

PMID- 23955323
TI  - Institutional and personal spirituality/religiosity and psychosocial adjustment
      in adolescence: concurrent and longitudinal associations.
AB  - Spirituality/religiosity is hypothesized to promote positive adjustment among
      adolescents. The goals of this study were to assess the unique and joint
      associations between two dimensions of spirituality/religiosity--institutional
      and personal--and a range of domains of psychosocial adjustment (intrapersonal
      well-being, quality of parent-child relationship, substance use, and academic
      orientation) and to evaluate the direction of effects in these associations.
      Participants included 803 predominately Canadian-born adolescents (53 % female)
      from Ontario, Canada, who completed a survey in grade 11 and grade 12. At the
      concurrent level, higher personal spirituality/religiosity consistently and
      uniquely predicted more positive adjustment in terms of well-being, parental
      relationship, and academic orientation. Higher institutional
      spirituality/religiosity uniquely and consistently predicted lower substance use,
      particularly when personal spirituality/religiosity also was high. With regard to
      the direction of effects (i.e., longitudinal associations), institutional
      spirituality/religiosity predicted lower future substance use. The results imply
      that the personal and institutional dimensions of spirituality/religiosity may be
      associated differentially with psychosocial adjustment, and it may be only in the
      domain of substance use that spirituality/religiosity predicts change in behavior
      over time.

PMID- 23955320
TI  - Neuroprotection in multiple sclerosis: a therapeutic approach.
AB  - Multiple sclerosis (MS) is a demyelinating disease of the central nervous system
      that is pathologically characterized by inflammatory demyelination and
      neurodegeneration. Axonal damage, along with neuronal loss, occurs from disease
      onset and may lead to progressive and permanent disability. In contrast with the
      inflammatory pathways, the molecular mechanisms leading to MS neurodegeneration
      remain largely elusive. With improved understanding of these mechanisms, new
      potential therapeutic targets for neuroprotection have emerged. We review the
      current understanding of neurodegenerative processes at play in MS and discuss
      potential outcome measures and targets for neuroprotection trials. 

PMID- 23955324
TI  - Relational victimization, loneliness and depressive symptoms: indirect
      associations via self and peer reports of rejection sensitivity.
AB  - Theory suggests that aversive social experiences generate emotional maladjustment
      because they prompt the development of a hypersensitivity to perceiving and
      overreacting to rejection. The primary aim of this study was to test hypothesized
      direct and indirect (via rejection sensitivity) links of overt/relational
      victimization and friendship conflict with early adolescents' loneliness and
      depressive symptoms. Participants were 366 Australian early adolescents age 10-14
      years (50.5 % girls). Using both a self-report and peer-report measure of
      rejection sensitivity, no difference was found when comparing the significant
      correlations of each measure with loneliness and depressive symptoms. Tests of
      direct and indirect associations with structural equation modeling showed that
      adolescents higher in relational victimization reported more loneliness and
      depressive symptoms and part of this association was by way of their greater self
      reports of rejection sensitivity and their peers' identification that they were
      higher in rejection sensitivity. Additionally, relational victimization was the
      only unique correlate of emotional maladjustment, and adolescents who reported
      more overt victimization were identified by their peers as higher in rejection
      sensitivity. Finally, gender and rejection sensitivity were tested as moderators.
      No gender moderation was found, but friendship conflict was associated more
      strongly with emotional maladjustment for adolescents low, rather than high, in
      rejection sensitivity. These findings identify relational victimization as
      particularly salient for emotional maladjustment both directly and indirectly via
      links with elevated rejection sensitivity. They show how rejection sensitivity
      and aversive experiences may contribute independently and jointly to emotional
      maladjustment for both boys and girls.

PMID- 23955325
TI  - Classification of human immunodeficiency virus-infected patients with chronic
      kidney disease using a combination of proteinuria and estimated glomerular
      filtration rate.
AB  - BACKGROUND: In 2012, the Kidney Disease: Improving Global Outcomes (KDIGO)
      updated the 2002 Kidney Disease Outcomes Quality Initiative (KDOQI) clinical
      practice guideline for chronic kidney disease (CKD). The 2012 KDIGO guideline
      elaborated the identification and prognosis of CKD by combining albuminuria with
      estimated glomerular filtration rate (eGFR). Identification of CKD with a high
      risk for a poor prognosis was investigated in human immunodeficiency virus (HIV)
      infected individuals by applying the new guideline. METHODS: A total of 1,447 HIV
      infected patients (1,351 male, 96 female; mean age 44.4 +/- 11.5 years) were
      classified using a combination of eGFR and dipstick proteinuria, as a convenient
      alternative to albuminuria. Proteinuria was classified into 3 grades-(A1) - and
      +/- , (A2) 1+ and 2+ , and (A3) 3+ and 4+. eGFR was classified into 6 grades-(G1)
      <=90, (G2) 60-89, (G3a) 45-59, (G3b) 30-44, (G4) 15-29, and (G5) <15 mL/min/1.73
      m(2). RESULTS: Mean CD4 cell count was 487 +/- 214 /MUL, with 80.7 % of patients
      having an undetectable HIV-RNA level. The prevalence of CKD stage <=2 and stage
      >=3 classified according to KDOQI staging was 93.4 and 6.6 %, respectively. Using
      the new KDIGO classification, the prevalence of CKD with either a low (green) or
      moderately increased (yellow) risk was 96.9 %, while the prevalence for a high
      (orange) and very high (red) risk was 3.1 %. CONCLUSION: The use of the new KDIGO
      classification may reduce the prevalence of HIV-infected CKD individuals who are
      at high risk for a poor prognosis by nearly a half.

PMID- 23955326
TI  - Should silicone prostheses be considered for specimen banking? A pilot study into
      their use for human biomonitoring.
AB  - Persistent organic pollutant (POP) biomonitoring in humans is challenging and
      generally carried out using blood, breast milk or adipose tissue, with
      concentrations normalised to the lipid content of the sample matrix. The goal of
      this cross-sectional pilot study was to evaluate the validity and feasibility of
      explanted silicone prostheses as a matrix for persistent organic pollutant
      biomonitoring in humans. We postulate that pollutant concentrations in silicone
      prostheses inserted in the body will equilibrate with that in the body over time
      and provide a measure of the overall body burden. This study included silicone
      prostheses from 22 female patients of the Colosseum clinic (Oslo, Norway)
      collected between September 2010 and April 2012. Absorption of chlorinated and
      brominated POPs into silicone prostheses during implantation was observed.
      Relative levels of the different contaminants measured in prostheses were in
      agreement with those from serum and breast milk analyses from the general
      Norwegian population. The comparison of serum and breast milk-based literature
      data with prosthesis concentrations transposed into lipid-normalised
      concentrations supports the validity of the prosthesis measurements. The median
      of relative percent differences between measurements with replicate silicone
      prostheses from 11 patients was below 30%. Observed increases in prosthesis
      concentrations with patients' age were found to be very similar to literature
      data from studies of the Norwegian population. Silicone prostheses therefore
      represent a promising matrix for the biomonitoring of nonpolar and non-ionic
      pollutants in humans. Sample accessibility and body burden representativeness of
      the silicone prostheses suggest that specimen banking should be initiated. 

PMID- 23955327
TI  - Development and application of simple pharmacokinetic models to study human
      exposure to di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP).
AB  - In a published controlled dosing experiment, a single individual consumed 5mg
      each of labeled di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) on
      separate occasions and tracked metabolites in his blood and urine over 48h. Data
      from this study were used to structure and calibrate simple pharmacokinetic (PK)
      models for these two phthalates, which predict urine and blood metabolite
      concentrations with a given phthalate intake scenario (times and quantities). The
      calibrated models were applied to a second published experiment in which 5
      individuals fasted over the course of a 48-h weekend (bottled water only), and
      their full urine voids were captured and measured for DnBP and DiBP metabolites.
      One goal of this model application was to confirm the validity of the calibrated
      models - their validity would be demonstrated if a profile of intakes could be
      found which adequately duplicated the metabolite concentrations measured in the
      urine. A second goal was to study patterns of exposure for this group. It was
      found that all metabolites could be duplicated very well with individual-specific
      "best-fit" intake scenarios, with one exception. It appears that the model
      predicted much lower concentrations of the metabolite, 3carboxy-mono
      propylphthalate (MCPP), than were observed in all individuals. Modeled as a
      metabolite of DnBP, this suggests that DnBP was not the major source of MCPP in
      the urine. For all 5 individuals, the reconstructed dose profiles of the two
      phthalates were similar: about 6 small bolus doses per day and an intake of about
      0.5MUg/kg-day. The intakes did not appear to be associated with diary-reported
      activities (personal hygiene and medication) of the participants. The modeled
      frequent intakes suggested one (or both) of two possibilities: ongoing exposures
      such as an inhalation exposure, or no exposure but rather an ongoing release of
      body stores of the phthalate metabolites from past exposures. 

PMID- 23955328
TI  - Avoiding burnout in new doctors: sleep, supervision and teams.

PMID- 23955329
TI  - Republished: novel insights into immune and inflammatory responses to respiratory
      viruses.
AB  - Viral lower respiratory tract infection (LRTI) can lead to severe disease at all
      ages, but with the exception of influenza vaccination, prevention is not
      available for most respiratory viruses, hence, effective, disease-limiting
      therapy is urgently required. To enable the development of novel effective
      therapeutic approaches, we need to improve understanding of the pathological
      mechanisms of viral LRTI. Here, we will discuss recently gained new insight into
      early, innate immune and inflammatory responses to respiratory viruses by airway
      epithelial cells and mucosal immune cells. Following virus recognition, these
      cells generate a range of mediators, including innate interferons,
      proinflammatory cytokines, and growth and differentiation factors which have
      pivotal roles in effective virus control, and the development of inflammation and
      disease in viral LRTI. 

PMID- 23955330
TI  - Republished: obesity and colorectal cancer.
AB  - Excess body weight, as defined by the body mass index (BMI), has been associated
      with several diseases and includes subjects who are overweight (BMI>=25-29.9
      kg/m(2)) or obese (BMI>=30 kg/m(2)). Overweight and obesity constitute the fifth
      leading risk for overall mortality, accounting for at least 2.8 million adult
      deaths each year. In addition around 11% of colorectal cancer (CRC) cases have
      been attributed to overweight and obesity in Europe. Epidemiological data suggest
      that obesity is associated with a 30-70% increased risk of colon cancer in men,
      whereas the association is less consistent in women. Similar trends exist for
      colorectal adenoma, although the risk appears lower. Visceral fat, or abdominal
      obesity, seems to be of greater concern than subcutaneous fat obesity, and any 1
      kg/m(2) increase in BMI confers additional risk (HR 1.03). Obesity might be
      associated with worse cancer outcomes, such as recurrence of the primary cancer
      or mortality. Several factors, including reduced sensitivity to antiangiogenic
      therapeutic regimens, might explain these differences. Except for wound
      infection, obesity has no significant impact on surgical procedures. The
      underlying mechanisms linking obesity to CRC are still a matter of debate, but
      metabolic syndrome, insulin resistance and modifications in levels of
      adipocytokines seem to be of great importance. Other biological factors such as
      the gut microbita or bile acids are emerging. Many questions still remain
      unanswered: should preventive strategies specifically target obese patients? Is
      the risk of cancer great enough to propose prophylactic bariatric surgery in
      certain patients with obesity? 

PMID- 23955331
TI  - First Australians.

PMID- 23955332
TI  - Three-dimensional culture using human plasma-medium gel with fragmin/protamine
      microparticles for proliferation of various human cells.
AB  - Fragmin/protamine microparticles (F/P MPs) have been used as carriers for the
      preservation and activation of cytokines in human plasma (HP)-Dulbecco's modified
      Eagle's medium (DMEM) gels. This study investigated a three-dimensional (3D)
      culture system using an HP-DMEM gel with 0.1 mg/mL F/P MPs and 5 ng/mL FGF-2 for
      the proliferation of human dermal fibroblast cells (DFCs), human microvascular
      endothelial cells (MVECs) and human coronary smooth muscle cells (SMCs), or 5
      ng/mL interleukin (IL)-3/granulocyte-macrophage colony-stimulating factor (GM
      CSF) for a human hematopoietic cell line (TF-1 cells). DFCs, MVECs, SMCs and TF-1
      cells grew rapidly under 3D culture conditions using a low-concentration HP (2 %)
      DMEM gel with F/P MPs and FGF-2 (for DFCs, MVECs and SMCs) or IL-3/GM-CSF (for TF
      1 cells) at doubling times of 22, 23, 25 and 18 h, respectively, without the use
      of animal serum, compared to under 2D culture conditions using low-concentration
      human serum (2 %)-DMEM with 5 ng/mL FGF-2 or IL-3/GM-CSF on F/P MP-coated plates
      at doubling times of approximately 26, 25, 40 and 20 h, respectively. 

PMID- 23955333
TI  - Tackling ethnic variations in asthma outcomes in New Zealand's Maori and Pacific
      children will need a long-term strategy.

PMID- 23955334
TI  - The flow-volume loop in inducible laryngeal obstruction: one component of the
      complete evaluation.

PMID- 23955335
TI  - Primary care challenges in treating paediatric asthma in the Asia-Pacific region.

PMID- 23955336
TI  - Can flow-volume loops be used to diagnose exercise induced laryngeal
      obstructions? A comparison study examining the accuracy and inter-rater agreement
      of flow volume loops as a diagnostic tool.
AB  - BACKGROUND: Pre- and post-exercise flow-volume loops are often recommended as an
      easy non-invasive method for diagnosing or excluding exercise-induced laryngeal
      obstructions in patients with exercise-related respiratory symptoms. However, at
      present there is no evidence for this recommendation. AIMS: To compare physician
      evaluated pre- and post-exercise flow-volume loops and flow data with
      laryngoscopic findings during exercise. METHODS: Data from 100 consecutive
      exercise tests with continuous laryngoscopy during the test were analysed.
      Laryngoscopic images were compared with the corresponding pre- and post-exercise
      flow-volume loops assessed by four separate physicians and with data from the
      loops (forced inspiratory flow (FIF) at 25% vs. FIF at 75% of forced inspiratory
      vital capacity (FIVC), forced expiratory flow at 50% of forced expiratory volume
      vs. FIF at 50% of FIVC, and FIVC vs. FIF at 50% of FIVC). RESULTS: There was no
      significant association between the laryngoscopic findings and the flow-volume
      data. There was no agreement between the four physicians in their assessment of
      the flow-volume loops (kappa <0.00), and none of the individual physician's
      assessments were significantly associated with the laryngoscopic findings.
      CONCLUSIONS: Exercise-induced laryngeal obstructions cannot be diagnosed or
      excluded by physician evaluated pre- and post-exercise flow-volume loops or flow
      data alone.

PMID- 23955337
TI  - Dopamine D2 receptor-mediated epidermal growth factor receptor transactivation
      through a disintegrin and metalloprotease regulates dopaminergic neuron
      development via extracellular signal-related kinase activation.
AB  - Dopamine D2 receptor (D2R)-mediated extracellular signal-regulated kinase (ERK)
      activation plays an important role in the development of dopaminergic
      mesencephalic neurons. Here, we demonstrate that D2R induces the shedding of
      heparin-binding epidermal growth factor (EGF) through the activation of a
      disintegrin and metalloprotease (ADAM) 10 or 17, leading to EGF receptor
      transactivation, downstream ERK activation, and ultimately an increase in the
      number of dopaminergic neurons and their neurite length in primary mesencephalic
      cultures from wild-type mice. These outcomes, however, were not observed in
      cultures from D2R knock-out mice. Our findings show that D2R-mediated ERK
      activation regulates mesencephalic dopaminergic neuron development via EGF
      receptor transactivation through ADAM10/17. 

PMID- 23955338
TI  - Fusion proteins and select lipids cooperate as membrane receptors for the soluble
      N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) Vam7p.
AB  - Vam7p, the vacuolar soluble Qc-SNARE, is essential for yeast vacuole fusion. The
      large tethering complex, homotypic fusion and vacuole protein sorting complex
      (HOPS), and phosphoinositides, which interact with the Vam7p PX domain, have each
      been proposed to serve as its membrane receptors. Studies with the isolated
      organelle cannot determine whether these receptor elements suffice and whether
      ligands or mutations act directly or indirectly on Vam7p binding to the membrane.
      Using pure components that are active in reconstituted vacuolar fusion, we now
      find that Vam7p binds to membranes through its combined affinities for several
      vacuolar membrane constituents: HOPS, phosphatidylinositol 3-phosphate, SNAREs,
      and acidic phospholipids. Acidic lipids allow low concentrations of Vam7p to
      suffice for fusion; without acidic lipids, the block to fusion is partially
      bypassed by high concentrations of Vam7p. 

PMID- 23955339
TI  - Functional inositol 1,4,5-trisphosphate receptors assembled from concatenated
      homo- and heteromeric subunits.
AB  - Vertebrate genomes code for three subtypes of inositol 1,4,5-trisphosphate (IP3)
      receptors (IP3R1, -2, and -3). Individual IP3R monomers are assembled to form
      homo- and heterotetrameric channels that mediate Ca(2+) release from
      intracellular stores. IP3R subtypes are regulated differentially by IP3, Ca(2+),
      ATP, and various other cellular factors and events. IP3R subtypes are seldom
      expressed in isolation in individual cell types, and cells often express
      different complements of IP3R subtypes. When multiple subtypes of IP3R are co
      expressed, the subunit composition of channels cannot be specifically defined.
      Thus, how the subunit composition of heterotetrameric IP3R channels contributes
      to shaping the spatio-temporal properties of IP3-mediated Ca(2+) signals has been
      difficult to evaluate. To address this question, we created concatenated IP3R
      linked by short flexible linkers. Dimeric constructs were expressed in DT40-3KO
      cells, an IP3R null cell line. The dimeric proteins were localized to membranes,
      ran as intact dimeric proteins on SDS-PAGE, and migrated as an ~1100-kDa band on
      blue native gels exactly as wild type IP3R. Importantly, IP3R channels formed
      from concatenated dimers were fully functional as indicated by agonist-induced
      Ca(2+) release. Using single channel "on-nucleus" patch clamp, the channels
      assembled from homodimers were essentially indistinguishable from those formed by
      the wild type receptor. However, the activity of channels formed from
      concatenated IP3R1 and IP3R2 heterodimers was dominated by IP3R2 in terms of the
      characteristics of regulation by ATP. These studies provide the first insight
      into the regulation of heterotetrameric IP3R of defined composition. Importantly,
      the results indicate that the properties of these channels are not simply a blend
      of those of the constituent IP3R monomers. 

PMID- 23955340
TI  - Centrosomal protein DZIP1 regulates Hedgehog signaling by promoting cytoplasmic
      retention of transcription factor GLI3 and affecting ciliogenesis.
AB  - The primary cilium is required for Hedgehog signaling. So far, all known
      ciliogenic proteins regulate Hedgehog signaling through their role in
      ciliogenesis. Here we show that the mouse DZIP1 regulates Hedgehog signaling
      through two mechanisms. First, DZIP1 interacts with GLI3, a transcriptional
      regulator for Hedgehog signaling, and prevents GLI3 from entering the nucleus.
      Second, DZIP1 is required for ciliogenesis. We show that DZIP1 colocalizes and
      interacts with CEP164, a protein localizing at appendages of the mother
      centrioles, and IFT88, a component of the intraflagellar transport (IFT)
      machinery. Functionally, both CEP164 and Ninein appendage proteins fail to
      localize to ciliary appendages in Dzip1 mutant cells; IFT components are not
      recruited to the basal body of cilia. Importantly, the accumulation of GLI3 in
      the nucleus is independent of loss of primary cilia in Dzip1 mutant cells.
      Therefore, DZIP1 is the first known ciliogenic protein that regulates Hedgehog
      signaling through a dual mechanism and that biochemically links IFT machinery
      with Hedgehog pathway components. 

PMID- 23955341
TI  - cAMP response element-binding protein (CREB) and nuclear factor kappaB mediate
      the tamoxifen-induced up-regulation of glutamate transporter 1 (GLT-1) in rat
      astrocytes.
AB  - Tamoxifen (TX), a selective estrogen receptor modulator, exerts antagonistic
      effects on breast tissue and is used to treat breast cancer. Recent evidence also
      suggests that it may act as an agonist in brain tissue. We reported previously
      that TX enhanced the expression and function of glutamate transporter 1 (GLT-1)
      in rat astrocytes, an effect that was mediated by TGF-alpha. To gain further
      insight into the mechanisms that mediate TX-induced up-regulation of GLT-1 (EAAT2
      in humans), we investigated its effect on GLT-1 at the transcriptional level. TX
      phosphorylated the cAMP response element-binding protein (CREB) and recruited
      CREB to the GLT-1 promoter consensus site. The effect of TX on astrocytic GLT-1
      was attenuated by the inhibition of PKA, the upstream activator of the CREB
      pathway. In addition, the effect of TX on GLT-1 promoter activity was abolished
      by the inhibition of the NF-kappaB pathway. Furthermore, TX recruited the NF
      kappaB subunits p65 and p50 to the NF-kappaB binding domain of the GLT-1
      promoter. Mutation of NF-kappaB (triple, -583/-282/-251) or CRE (-308) sites on
      the GLT-1 promoter led to significant repression of the promoter activity, but
      neither mutant completely abolished the TX-induced GLT-1 promoter activity.
      Mutation of both the NF-kappaB (-583/-282/-251) and CRE (-308) sites led to a
      complete abrogation of the effect of TX on GLT-1 promoter activity. Taken
      together, our findings establish that TX regulates GLT-1 via the CREB and NF
      kappaB pathways. 

PMID- 23955342
TI  - F-box and WD repeat domain-containing-7 (Fbxw7) protein targets endoplasmic
      reticulum-anchored osteogenic and chondrogenic transcriptional factors for
      degradation.
AB  - Although identification of substrates for an enzyme is a key step in elucidation
      of its biological functions, detection of the interaction between enzymes and
      substrates remains challenging. We recently developed a new approach, termed
      differential proteomics-based identification of ubiquitylation substrates
      (DiPIUS), for the discovery of substrates of ubiquitin ligases. We have now
      applied this approach to Fbxw7, the F-box protein component of an Skp1-Cul1-F-box
      protein-type ubiquitin ligase and, thereby, identified two similar transcription
      factors, old astrocyte specifically induced substance (OASIS) and BBF2 human
      homolog on chromosome 7 (BBF2H7), as candidate substrates. Coimmunoprecipitation
      analysis confirmed that the alpha and gamma isoforms of Fbxw7 interact with OASIS
      and BBF2H7 in vivo. Sustained overexpression of Fbxw7 resulted in marked down
      regulation of OASIS and BBF2H7, whereas RNAi-mediated Fbxw7 depletion stabilized
      both proteins. Mutation of a putative Cdc4 phosphodegron in OASIS and BBF2H7
      attenuated their association with Fbxw7 and resulted in their stabilization.
      Depletion of Fbxw7 promoted the differentiation of mouse C2C12 mesenchymal cells
      into osteoblasts in association with the accumulation of OASIS. Conversely,
      overexpression of Fbxw7 in C2C12 cells resulted in down-regulation of Col1A1
      mRNA, a target of OASIS. Conditional ablation of Fbxw7 in primary mouse
      mesenchymal cells promoted chondrogenesis in association with up-regulation of
      BBF2H7, whereas overexpression of Fbxw7 inhibited chondrogenesis in ATDC5 cells.
      Collectively, our results suggest that OASIS and BBF2H7 are bona fide substrates
      of Fbxw7 and that Fbxw7 controls osteogenesis and chondrogenesis by targeting
      OASIS and BBF2H7, respectively, for degradation. 

PMID- 23955343
TI  - Catalytic mechanism of 5-chlorohydroxyhydroquinone dehydrochlorinase from the
      YCII superfamily of largely unknown function.
AB  - TftG, 5-chloro-2-hydroxyhydroquinone (5-CHQ) dehydrochlorinase, is involved in
      the biodegradation of 2,4,5-trichlorophenoxyacetate by Burkholderia
      phenoliruptrix AC1100. It belongs to the YCII superfamily, a group of proteins
      with largely unknown function. In this work, we utilized structural and
      functional studies, including the apo-form and 2,5-dihydroxybenzoquinone binary
      complex crystal structures, computational analysis, and site-directed
      mutagenesis, to determine the dehydrochlorination mechanism. The His-Asp dyad,
      which initiates catalysis, is strongly conserved in YCII-like proteins. In
      addition, other catalytically important residues such as Pro-76, which orients
      the His-Asp catalytic dyad; Arg-17 and Ser-56, which form an oxyanion hole; and
      Asp-9, which stabilizes the oxyanion hole, are among the most highly conserved
      residues across the YCII superfamily members. The comprehensive characterization
      of TftG helps not only for identifying effective mechanisms for chloroaromatic
      dechlorination but also for understanding the functions of YCII superfamily
      members, which we propose to be lyases. 

PMID- 23955345
TI  - Epidemiology of heart failure in Asia.
AB  - Heart failure (HF) is a global epidemic in health care and a leading cause of
      mortality and morbidity worldwide. In Asian countries, causes of mortality and
      morbidity have shifted or have been shifting from infectious diseases and/or
      nutritional deficiencies to lifestyle-related diseases, such as cardiovascular
      disease, cancers and diabetes, in conjunction with the transition from developing
      to developed countries during the past decades (so-called "the epidemiologic
      transition"). Because the effect of this epidemiologic transition varies among
      countries, the etiology, prevalence, management and outcomes of HF also differ
      among the countries. Thus, we need to assemble and comprehensively analyze the
      available evidence to date for daily HF practice in Asia and to systematically
      conduct future epidemiologic approaches to establishing appropriate prevention
      programs against the burden of HF in Asia. This review article will briefly
      update the epidemiology of HF in Asia.

PMID- 23955346
TI  - Transgenic expression and functional characterization of human platelet derived
      growth factor BB (hPDGF-BB) in tobacco (Nicotiana tabacum L.).
AB  - Recombinant human platelet derived growth factor BB (rhPDGF-BB) is clinically
      approved for treating diabetic neuropathic ulcers. Plant-based expression systems
      offer less expensive ways of producing recombinant drugs, which do not require
      purification for clinical use. From this perspective, rhPDGF-BB is an ideal
      candidate for expression in plants as it can be applied topically. Here, we
      report a proof of concept study, in which rhPDGF-BB was expressed in tobacco
      plants, and its biological activity was tested in vitro. The mature human
      platelet derived growth factor BB (hPDGF-BB) gene was codon-optimized for tobacco
      and fused with ER targeting and retention signals, 5' and 3' UTRs of arc5-1 gene
      along with CaMV 35S promoter, and then, transferred by Agrobacterium-mediated
      transformation. Gene and protein expression of hPDGF-BB were confirmed by PCR and
      immunoblot studies. Bioactivity of hPDGF-BB expressed protein was determined by
      in vitro assays such as proliferation and migration in NIH3T3 cells. Our data
      reveals that total soluble proteins containing hPDGF-BB from transgenic plants
      showed a 4.5-fold increase in fibroblast proliferation compared to non-transgenic
      plants. Furthermore, plant-made rhPDGF-BB induced chemotaxis of treated cells and
      promoted wound healing in vitro. These results clearly demonstrate that
      functionally active rhPDGF-BB protein can be produced in plants and might have
      therapeutic benefits. 

PMID- 23955347
TI  - Quenching action of monofunctional sulfur mustard on chlorophyll fluorescence:
      towards an ultrasensitive biosensor.
AB  - An ultrasensitive fluorimetric biosensor for the detection of chemical warfare
      agent sulfur mustard (SM) was developed using its monofunctional analogue. SM is
      a vesicant and a potent chemical threat owing to its direct toxic effects on
      eyes, lungs, skin and DNA. This work investigates the quenching action of the
      analyte on chlorophyll fluorescence as elucidated by nuclear magnetic resonance,
      Fourier transform infrared spectroscopy and mass spectrometry studies suggesting
      the electrophilic attack of carbonium ion on nitrogens of the porphyrin moiety of
      chlorophyll. The properties of immobilisation matrix were optimised and scanning
      electron microscope observations confirmed improvement in pore size of sol-gels
      by addition of 32 % (v/v) glycerol, a feature enabling enhanced sensitivity
      towards the analyte. Chlorophyll embedded sol-gel was treated with increasing
      concentrations of monofunctional SM and the corresponding drop in maximum
      fluorescence intensity as measured by emission at 673 nm was observed, which
      varied linearly and had a detection limit of 7.68 * 10(-16) M. The biosensor was
      found to be 6 orders of magnitude more sensitive than the glass microfibre-based
      disc biosensor previously reported by us. 

PMID- 23955344
TI  - Pre-existent asymmetry in the human cyclooxygenase-2 sequence homodimer.
AB  - Prostaglandin endoperoxide H synthase-2 (PGHS-2), also known as cyclooxygenase-2
      (COX-2), is a sequence homodimer. However, the enzyme exhibits half-site heme and
      inhibitor binding and functions as a conformational heterodimer having a
      catalytic subunit (Ecat) with heme bound and an allosteric subunit (Eallo)
      lacking heme. Some recombinant heterodimers composed of a COX-deficient mutant
      subunit and a native subunit (i.e. Mutant/Native PGHS-2) have COX activities
      similar to native PGHS-2. This suggests that the presence of heme plus substrate
      leads to the subunits becoming lodged in a semi-stable Eallo-mutant/Ecat
      Native~heme form during catalysis. We examined this concept using human PGHS-2
      dimers composed of combinations of Y385F, R120Q, R120A, and S530A mutant or
      native subunits. With some heterodimers (e.g. Y385F/Native PGHS-2), heme binds
      with significantly higher affinity to the native subunit. This correlates with
      near native COX activity for the heterodimer. With other heterodimers (e.g.
      S530A/Native PGHS-2), heme binds with similar affinities to both subunits, and
      the COX activity approximates that expected for an enzyme in which each monomer
      contributes equally to the net COX activity. With or without heme, aspirin
      acetylates one-half of the subunits of the native PGHS-2 dimer, the Ecat
      subunits. Subunits having an S530A mutation are refractory to acetylation.
      Curiously, aspirin acetylates only one-quarter of the monomers of S530A/Native
      PGHS-2 with or without heme. This implies that there are comparable amounts of
      two noninterchangeable species of apoenzymes, Eallo-S530A/Ecat-Native and Eallo
      Native/Ecat-S530A. These results suggest that native PGHS-2 assumes a reasonably
      stable, asymmetric Eallo/Ecat form during its folding and processing. 

PMID- 23955348
TI  - Production and characterization of a halo-, solvent-, thermo-tolerant alkaline
      lipase by Staphylococcus arlettae JPBW-1, isolated from rock salt mine.
AB  - Studies on lipase production and characterization were carried out with a
      bacterial strain Staphylococcus arlettae JPBW-1 isolated from rock salt mine,
      Darang, HP, India. Higher lipase activity has been obtained using 10 % inoculum
      with 5 % of soybean oil as carbon source utilizing a pH 8.0 in 3 h at 35  degrees
      C and 100 rpm through submerged fermentation. Partially purified S. arlettae
      lipase has been found to be active over a broad range of temperature (30-90 
      degrees C), pH (7.0-12.0) and NaCl concentration (0-20 %). It has shown extreme
      stability with solvents such as benzene, xylene, n-hexane, methanol, ethanol and
      toluene up to 30 % (v/v). The lipase activity has been found to be inhibited by
      metal ions of K(+), Co(2+) and Fe (2+) and stimulated by Mn(2+), Ca(2+) and
      Hg(2+). Lipase activity has been diminished with denaturants, but enhanced effect
      has been observed with surfactants, such as Tween 80, Tween 40 and chelator EDTA.
      The K m and V max values were found to be 7.05 mM and 2.67 mmol/min,
      respectively. Thus, the lipase from S. arlettae may have considerable potential
      for industrial application from the perspectives of its tolerance towards
      industrial extreme conditions of pH, temperature, salt and solvent. 

PMID- 23955349
TI  - Tailoring the pH dependence of human non-pancreatic secretory phospholipase A2 by
      engineering surface charges.
AB  - Human non-pancreatic secretory phospholipase A2 (hnpsPLA2) catalyzes the sn-2
      acyl hydrolysis of phospholipids. It was reported that hnpsPLA2 is involved in
      various diseases like inflammation, cancer, and so on. This enzyme also exhibits
      anti-bacterial and anti-virus activities. It is active over a broad pH range,
      with higher activity at alkaline conditions. In order to make it suitable as a
      potential bactericide, high activity at neutral pH is preferable. We have tried
      to tailor the pH dependence of hnpsPLA2 activity by replacing its surface charged
      residues. Three surface charge replacements, Arg42Glu, Arg100Glu, and Glu89Lys,
      showed increased activities at neutral pH, which are 2.3, 2.8, and 2.3 times that
      of the wild-type enzyme at pH 7. Both the positive-to-negative and negative-to
      positive mutations lowered the optimum enzymatic reaction pH of hnpsPLA2,
      indicating that the enzyme pH profile depends on a delicate balance of charged
      residues. The activity changes are in good agreement with the recently proposed
      calcium-coordinated catalytic triad mechanism. This study also provides a general
      means of enhancing hnpsPLA2 activity at low pH. 

PMID- 23955350
TI  - Enhanced hydrolysis and acidification of waste activated sludge by biosurfactant
      rhamnolipid.
AB  - The effect of biosurfactant rhamnolipid (RL) on hydrolysis and acidification of
      waste activated sludge (WAS) was investigated. The results indicated that RL
      could greatly reduce the surface tension of sludge, resulting in stimulating the
      hydrolysis rate of WAS and enhancing the production of short-chain fatty acids
      (SCFAs). With the increase of RL dosage from 0.2 to 0.5 g/g DS, the maximum
      soluble chemical oxygen demand (SCOD), protein and carbohydrate concentration
      increased correspondingly. After 6 h of hydrolysis, SCOD, protein and
      carbohydrate concentration increased from 371.9, 93.3 and 9.0 mg/l to 3,994.5,
      800.0 and 401.4 mg/l at RL 0.3 g/g DS, respectively. Furthermore, the release of
      NH4 (+)-N, PO4 (3-)-P and the accumulation of SCFAs also improved in the presence
      of RL. The maximum SCFAs was 1,829.9 mg COD/l at RL 0.3 g/g DS, while it was only
      377.7 mg COD/l for the blank test. The propionic acid and acetic acid were the
      mainly SCFAs produced, accounting for 50-60% of total SCFAs. 

PMID- 23955351
TI  - A novel polysaccharide from Lentinus edodes Mycelia exhibits potential antitumor
      activity on laryngeal squamous cancer cell line Hep-2.
AB  - A novel polysaccharide [Lentinus edodes mycelia polysaccharide 2 (LMP2)] with a
      molecular weight of 2.27 * 10(4) Da was isolated from the Lentinus edodes mycelia
      and purified by Sephadex G-200 and diethylaminoethyl-32 column chromatography.
      HPLC results indicated that LMP2 contained mannose, arabinose, galactose, xylose,
      and rhamnose with a relative molar ratio of 1:0.74:3.23:1.18:10.98. Its antitumor
      activity was evaluated in vitro by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay, colony formation assay, and transwell assay.
      LMP2 showed a remarkable inhibitory effect on the proliferation of Hep-2 cells,
      and at the concentration of 200 mg/ml, the inhibition ratio was 37.2 % after 72
      h. Furthermore, colony formation of Hep-2 cells was reduced significantly after
      treatment with LMP2. Invasion of Hep-2 cells was inhibited significantly by LMP2.
      These results suggested that LMP2 could be explored as a potential antitumor
      material for laryngeal carcinoma. 

PMID- 23955353
TI  - From glue to gasoline: how competition turns perspective takers unethical.
AB  - Perspective taking is often the glue that binds people together. However, we
      propose that in competitive contexts, perspective taking is akin to adding
      gasoline to a fire: It inflames already-aroused competitive impulses and leads
      people to protect themselves from the potentially insidious actions of their
      competitors. Overall, we suggest that perspective taking functions as a
      relational amplifier. In cooperative contexts, it creates the foundation for
      prosocial impulses, but in competitive contexts, it triggers hypercompetition,
      leading people to prophylactically engage in unethical behavior to prevent
      themselves from being exploited. The experiments reported here establish that
      perspective taking interacts with the relational context--cooperative or
      competitive--to predict unethical behavior, from using insidious negotiation
      tactics to materially deceiving one's partner to cheating on an anagram task. In
      the context of competition, perspective taking can pervert the age-old axiom "do
      unto others as you would have them do unto you" into "do unto others as you think
      they will try to do unto you."

PMID- 23955352
TI  - Direct growth of graphene film on germanium substrate.
AB  - Graphene has been predicted to play a role in post-silicon electronics due to the
      extraordinary carrier mobility. Chemical vapor deposition of graphene on
      transition metals has been considered as a major step towards commercial
      realization of graphene. However, fabrication based on transition metals involves
      an inevitable transfer step which can be as complicated as the deposition of
      graphene itself. By ambient-pressure chemical vapor deposition, we demonstrate
      large-scale and uniform depositon of high-quality graphene directly on a Ge
      substrate which is wafer scale and has been considered to replace conventional Si
      for the next generation of high-performance metal-oxide-semiconductor field
      effect transistors (MOSFETs). The immiscible Ge-C system under equilibrium
      conditions dictates graphene depositon on Ge via a self-limiting and surface
      mediated process rather than a precipitation process as observed from other
      metals with high carbon solubility. Our technique is compatible with modern
      microelectronics technology thus allowing integration with high-volume production
      of complementary metal-oxide-semiconductors (CMOS). 

PMID- 23955354
TI  - The reappropriation of stigmatizing labels: the reciprocal relationship between
      power and self-labeling.
AB  - We present a theoretical model of reappropriation--taking possession of a slur
      previously used exclusively by dominant groups to reinforce another group's
      lesser status. Ten experiments tested this model and established a reciprocal
      relationship between power and self-labeling with a derogatory group term. We
      first investigated precursors to self-labeling: Group, but not individual, power
      increased participants' willingness to label themselves with a derogatory term
      for their group. We then examined the consequences of such self-labeling for both
      the self and observers. Self-labelers felt more powerful after self-labeling, and
      observers perceived them and their group as more powerful. Finally, these labels
      were evaluated less negatively after self-labeling, and this attenuation of
      stigma was mediated by perceived power. These effects occurred only for
      derogatory terms (e.g., queer, bitch), and not for descriptive (e.g., woman) or
      majority-group (e.g., straight) labels. These results suggest that self-labeling
      with a derogatory label can weaken the label's stigmatizing force.

PMID- 23955355
TI  - Giving preschoolers choice increases sharing behavior.
AB  - Young children are remarkably prosocial, but the mechanisms driving their
      prosociality are not well understood. Here, we propose that the experience of
      choice is critically tied to the expression of young children's altruistic
      behavior. Three- and 4-year-olds were asked to allocate resources to an
      individual in need by making a costly choice (allocating a resource they could
      have kept for themselves), a noncostly choice (allocating a resource that would
      otherwise be thrown away), or no choice (following instructions to allocate the
      resource). We measured subsequent prosociality by allowing children to then
      allocate new resources to a new individual. Although the majority of children
      shared with the first individual, children who were given costly alternatives
      shared more with the new individual. Results are discussed in terms of a
      prosocial-construal hypothesis, which suggests that children rationally infer
      their prosociality through the process of making difficult, autonomous choices. 

PMID- 23955356
TI  - The relative trustworthiness of inferential tests of the indirect effect in
      statistical mediation analysis: does method really matter?
AB  - A content analysis of 2 years of Psychological Science articles reveals
      inconsistencies in how researchers make inferences about indirect effects when
      conducting a statistical mediation analysis. In this study, we examined the
      frequency with which popularly used tests disagree, whether the method an
      investigator uses makes a difference in the conclusion he or she will reach, and
      whether there is a most trustworthy test that can be recommended to balance
      practical and performance considerations. We found that tests agree much more
      frequently than they disagree, but disagreements are more common when an indirect
      effect exists than when it does not. We recommend the bias-corrected bootstrap
      confidence interval as the most trustworthy test if power is of utmost concern,
      although it can be slightly liberal in some circumstances. Investigators
      concerned about Type I errors should choose the Monte Carlo confidence interval
      or the distribution-of-the-product approach, which rarely disagree. The
      percentile bootstrap confidence interval is a good compromise test. 

PMID- 23955357
TI  - [Gender medicine - geriatrics].

PMID- 23955358
TI  - [Gender-related aspects of family caregiving].
AB  - Most people in need of care and assistance are currently still being cared for at
      home by family members. The majority of family caregivers are women. However, the
      percentage of men assuming the role of main caregiver at home is increasing. This
      may point to a change in the distribution of caregiving within the family. The
      health-related and social stresses and strains affecting cargiving persons also
      show gender-specific differences and are experienced more frequently and with a
      higher intensity by female caregivers than caregiving men. Men approach the
      challenge of caring differently to women and also organize care differently to
      female family caregivers. Although a high percentage of those providing informal
      care to family members at home are now men, this fact is hardly appreciated by
      society. In the specialist literature, caring men are often seen from the
      perspective of women. This article aims to portray gender-specific perspectives
      concerning the situation of providing informal care and assistance to elderly
      people and the stresses and strains that are associated with it. 

PMID- 23955360
TI  - [Communications of the DGGG (German Society of Gerontology and Geriatrics ).
      Report of the president].

PMID- 23955359
TI  - [Lipid lowering therapy in geriatric patients].
AB  - Cardiovascular disease is also the most frequent cause of mortality in the
      elderly population. Invasive diagnostic and therapeutic interventions are
      performed at an increasing rate in older patients in order to maintain functional
      capacities and, thus, an adequate quality of life. Thus, strategies to prevent
      cardiovascular events (e.g., lipid lowering therapy) are also of great importance
      in elderly. With respect to the side effects of statin therapy, the risk of drug
      interaction has to be considered, as well as myopathy. Discrepant study results
      exist about the influence of statins on cognitive function. Retrospective
      analyses indicate that statin therapy might be related to an increased risk for
      type.2 diabetes in certain risk groups. The indication for statin therapy should,
      therefore, consider the risk profile and especially the individual situation of
      the older patient.

PMID- 23955362
TI  - [Communications of the German Society for Geriatrics (DGG). Hof 2013: congress
      highlights].

PMID- 23955361
TI  - [Communications of the German Federation of Geriatrics (BV Geriatrics). News
      August / September].

PMID- 23955363
TI  - [Communications of the Austrian Society for Geriatrics and Gerontology (OGGG). A
      Choosing Wisely initiative for Austria].

PMID- 23955364
TI  - Metalloenzymes: Cutting out the middleman.
AB  - In vivo, hydrogenases require maturases for active site incorporation. However,
      in vitro, an active site model with limited catalytic activity could be
      incorporated into the apo form of [FeFe]-hydrogenase without the aid of
      maturases, generating enzyme with native activity.

PMID- 23955365
TI  - Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration.
AB  - Pregnenolone (P5) is a neurosteroid that improves memory and neurological
      recovery. It is also required for zebrafish embryonic development. However, its
      mode of action is unclear. Here we show that P5 promotes cell migration and
      microtubule polymerization by binding a microtubule plus end-tracking protein,
      cytoplasmic linker protein 1 (CLIP-170). We captured CLIP-170 from zebrafish
      embryonic extract using a P5 photoaffinity probe conjugated to
      diaminobenzophenone. P5 interacted with CLIP-170 at its coiled-coil domain and
      changed it into an extended conformation. This increased CLIP-170 interaction
      with microtubules, dynactin subunit p150(Glued) and LIS1; it also promoted CLIP
      170-dependent microtubule polymerization. CLIP-170 was essential for P5 to
      promote microtubule abundance and zebrafish epiboly cell migration during
      embryogenesis, and overexpression of the P5-binding region of CLIP-170 delayed
      this migration. P5 also sustained migration directionality of cultured mammalian
      cells. Our results show that P5 activates CLIP-170 to promote microtubule
      polymerization and cell migration. 

PMID- 23955366
TI  - NO-inducible nitrosothionein mediates NO removal in tandem with thioredoxin.
AB  - Nitric oxide (NO) is a toxic reactive nitrogen species that induces microbial
      adaption mechanisms. Screening a genomic DNA library identified a new gene, ntpA,
      that conferred growth tolerance upon Aspergillus nidulans against exogenous NO.
      The gene encoded a cysteine-rich 23-amino-acid peptide that reacted with NO and S
      nitrosoglutathione to generate an S-nitrosated peptide. Disrupting ntpA increased
      amounts of cellular S-nitrosothiol and NO susceptibility. Thioredoxin and its
      reductase denitrosated the S-nitrosated peptide, decreased cellular S
      nitrosothiol and conferred tolerance against NO, indicating peptide-mediated
      catalytic NO removal. The peptide binds copper(I) in vitro but is dispensable for
      metal tolerance in vivo. NO but not metal ions induced production of the peptide
      and ntpA transcripts. We discovered that the thionein family of peptides has NO
      related functions and propose that the new peptide be named NO-inducible
      nitrosothionein (iNT). The ubiquitous distribution of iNT-like polypeptides
      constitutes a potent NO-detoxifying mechanism that is conserved among various
      organisms. 

PMID- 23955367
TI  - Reference ranges for sonographic dimensions of the liver and spleen in preterm
      infants.
AB  - BACKGROUND: Preterm infants usually have multiple comorbidities that affect
      spleen and liver. Ultrasonographic measurement of organ sizes is an important and
      reliable parameter in evaluation of spleen and liver pathology in preterm
      newborns. OBJECTIVE: The purpose of this study was to determine reference values
      of ultrasonographic measurements of the liver and spleen in preterm newborns.
      MATERIALS AND METHODS: We prospectively performed sonography on 498 preterm
      newborns in the first week of life. We measured spleen and liver dimensions and
      statistically analyzed relationships between the dimensions and gender,
      gestational age (based on mother's last menstrual period), height and weight.
      Reference ranges of dimensions were defined. RESULTS: Longitudinal and
      anteroposterior dimensions of the liver and spleen were statistically
      significantly different between the boys and girls (P < 0.05) and showed high
      correlation with the gestational age, weight and height. Weight was the parameter
      best correlated with the dimensions. CONCLUSION: Nomograms from these data are
      useful for sonographic evaluation of the liver and spleen in preterm newborns.

PMID- 23955368
TI  - Imaging features of juxtacortical chondroma in children.
AB  - BACKGROUND: Juxtacortical chondroma is a rare benign bone lesion in children.
      Children usually present with a mildly painful mass, which prompts diagnostic
      imaging studies. The rarity of this condition often presents a diagnostic
      challenge. Correct diagnosis is crucial in guiding surgical management.
      OBJECTIVE: To describe the characteristic imaging findings of juxtacortical
      chondroma in children. MATERIALS AND METHODS: We identified all children who were
      diagnosed with juxtacortical chondroma between 1998 and 2012. A single
      experienced pediatric radiologist reviewed all diagnostic imaging studies,
      including plain radiographs, CT, MR and bone scans. RESULTS: Seven children (5
      boys and 2 girls) with juxtacortical chondroma were identified, ranging in age
      from 6 years to 16 years (mean 12.3 years). Mild pain and a palpable mass were
      present in all seven children. Plain radiographs were available in 6/7, MR in
      7/7, CT in 4/7 and skeletal scintigraphy in 5/7 children. Three lesions were
      located in the proximal humerus, with one each in the distal radius, distal
      femur, proximal tibia and scapula. Radiographic and CT features deemed highly
      suggestive of juxtacortical chondroma included cortical scalloping, underlying
      cortical sclerosis and overhanging margins. MRI features consistent with
      juxtacortical chondroma included isointensity to skeletal muscle on T1, marked
      hyperintensity on T2 and peripheral rim enhancement after contrast agent
      administration. One of seven lesions demonstrated intramedullary extension, and
      2/7 showed adjacent soft-tissue edema. CONCLUSION: Juxtacortical chondroma is an
      uncommon benign lesion in children with characteristic features on plain
      radiographs, CT and MR. Recognition of these features is invaluable in guiding
      appropriate surgical management.

PMID- 23955369
TI  - Honorary authorship in biomedical journals: how common is it and why does it
      exist?
AB  - BACKGROUND: The number of coauthors in the medical literature has increased over
      the past 50 years as authorship continues to have important academic, social and
      financial implications. AIM AND METHOD: The study aim was to determine the
      prevalence of honorary authorship in biomedical publications and identify the
      factors that lead to its existence. An email with a survey link was sent
      anonymously to 9283 corresponding authors of PubMed articles published within 1
      year of contact. RESULTS: A completed survey was obtained from 1246 corresponding
      authors, a response rate of 15.75%. One-third (33.4%) admitted that they had
      added authors who did not deserve authorship credit. Origin of the study from
      Europe and Asia (p <= 0.001 and 0.005, respectively), study type as case
      report/case series (p=0.036) and increasing number of coauthors were found to be
      the associated factors on multivariate analysis. Journal impact factor was also
      found to be associated with honorary authorship (mean journal impact factor was
      4.82 (SD 6.32) for those who self-reported honorary authorship and 5.60 (SD 7.13)
      for those who did not report unjust authorship, p=0.05). In retrospect, 75% of
      the authors indicated that they would remove unjustified names from the
      authorship list. Reasons for adding honorary authors were complimentary (39.4%),
      to avoid conflict at work (16.1%), to facilitate article acceptance (7.2%), and
      other (3.6%). CONCLUSIONS: Honorary authorship is relatively common in biomedical
      publications. Researchers should comply with the International Committee of
      Medical Journal Editors' criteria for authorship.

PMID- 23955371
TI  - The effects of surgery on locomotion in elderly patients with cervical
      spondylotic myelopathy.
AB  - PURPOSE: This study aimed to evaluate the effects of surgery on locomotor ability
      in patients with cervical spondylotic myelopathy (CSM) and compare the results
      between elderly and younger patients. METHODS: A total of 369 consecutive
      patients who underwent expansive laminoplasty for CSM were prospectively
      analysed. Patients were divided into two age groups of >= 75 years (elderly
      group, 76 patients) and <75 years (younger group, 293 patients). Locomotor
      ability was estimated using part of the functional independence measure (FIM).
      The sum of gait and stairs items [functional independence measure (locomotion),
      FIM-L; possible scores, 2-14] and neurological status were estimated using the
      Japanese Orthopaedic Association (JOA) score (possible score, 0-17). Pre
      operative neurological anamnesis was reviewed, and the surgical results of
      elderly patients with or without co-existing neurological history were evaluated
      to determine the origin of locomotor disability. RESULTS: Peri-operative FIM-L
      and JOA scores were significantly lower in the elderly group than in the younger
      group, and the opposite was true for improved FIM score. Cerebral infarction and
      previous lumbar surgery were identified as neurological co-morbidities in the
      elderly group. However, there was no significant difference in surgical results
      between elderly patients with and without co-existing neurological disorders.
      CONCLUSIONS: Decompression surgery can improve locomotor ability and decrease
      nursing care requirements among elderly patients with CSM. However, other
      neurological diseases can co-exist in elderly patients, making it difficult to
      diagnose the origin of locomotor disability. Therefore, detailed peri-operative
      work-up and timely decompression should be given priority to avoid progression
      towards fixed locomotor disability.

PMID- 23955370
TI  - Classification system of the sagittal standing alignment in young adolescent
      girls.
AB  - PURPOSE: The purpose of this cohort study was to classify sagittal standing
      alignment of pre-peak height velocity (pre-PHV) girls, and to evaluate whether
      identified subgroups were associated with measures of spinal pain. This study
      further aimed at drawing attention to similarities and differences between the
      current postural classification and a previous system determined among pre-PHV
      boys. METHODS: 557 pre-PHV girls [mean age, 10.6 years (SD, 0.47 years)]
      participated in the study. Three gross body segment orientation parameters and
      five specific lumbopelvic characteristics were quantified during habitual
      standing. Postural subgroups were determined by cluster analysis. Logistic
      regression was applied to assess the relationship between postural subgroups and
      spinal pain measures (pain and seeking care, assessed by self-administered
      questionnaire). Chi-square statistics, independent samples T test, and
      distribution-based methods were used for comparison with postural categorization
      in pre-PHV boys. RESULTS AND CONCLUSION: Among pre-PHV girls, clinically
      meaningful posture clusters emerged both on the gross body segment and specific
      lumbopelvic level. The postural subtypes identified among pre-PHV girls closely
      corresponded to those previously described in pre-PHV boys, thereby allowing the
      use of the same, working nomenclature. In contrast to previous findings among pre
      PHV boys, no associations between posture clusters and spinal pain measures were
      significant in girls at pre-PHV age. When comparing discrete 'global' alignment
      scores across corresponding posture types, some intriguing differences were found
      between genders which might involve different biomechanical loading patterns.
      Whether habitual posture forms a risk factor for developing spinal pain up to
      adulthood needs evaluation in prospective multifactorial follow-up research.

PMID- 23955372
TI  - Orexins (hypocretins) contribute to fear and avoidance in rats exposed to a
      single episode of footshocks.
AB  - Orexins (hypocretins) are peptides that have been shown to regulate behavioral
      arousal and wakefulness. Recent evidence indicates that orexin neurons are
      activated by stress and that orexins play a role in anxiety. The present paper
      describes a series of experiments that examined whether orexins are involved in
      the anxiety that resulted from exposing rats to an acute episode of footshocks (5
      * 2 s of 1.5 mA shocks). We found that prepro-orexin (ppOX) mRNA was elevated in
      rats at 6 and 14 days after exposure to footshock and that ppOX mRNA levels were
      correlated with fear at 14 days post-shock. Systemic injections of the non
      selective dual orexin receptor antagonist TCS-1102 (10 and 20 mg/kg, i.p.) were
      found to decrease fear and anxiety in rats 14 days after exposure to footshock.
      We also found that rats that exhibited a high level of immobility to a novel tone
      the day after the footshock episode (high responders, HR) showed significantly
      elevated levels of ppOX mRNA at 14 days post-shock compared to control rats.
      Furthermore, TCS-1102 (10 mg/kg, i.p.) was found to have anxiolytic effects that
      were specific for HR when tested in the elevated T-maze. This study provides
      evidence linking the orexin system to the anxiety produced by exposure of rats to
      a single episode of footshocks. It also provides preclinical evidence in support
      of the use of orexin antagonists for the treatment of anxiety in response to an
      acute episode of stress. 

PMID- 23955373
TI  - Development of a nose cream containing the synthetic antimicrobial peptide
      P60.4Ac for eradication of methicillin-resistant Staphylococcus aureus carriage.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) infections are an increasing
      problem, and current treatment options are suboptimal. Nasal carriage of MRSA is
      a major risk factor for infection, but nasal eradication strategies are
      increasingly considered to be insufficiently effective. In this study, a water-in
      oil cream formulation was developed for nasal application with an antimicrobial
      peptide, P60.4Ac, aimed at the eradication of MRSA carriage. Quality control of
      the cream included the measurement of the content and release of the peptide by a
      validated high-performance liquid chromatography method. Stability of the peptide
      in the formulation was investigated including the evaluation of the effect of
      stress conditions. Preliminary shelf-life study of the drug formulation
      demonstrated that the peptide is stable in the formulation at least for 5 months.
      Microbial-killing assays with MRSA LUH14616 as a target demonstrated the dose
      dependent antimicrobial activity of the peptide formulation.

PMID- 23955374
TI  - Unexpected mild C-N bond cleavage mediated by guanidine coordination to a niobium
      iminocarbamoyl complex.
AB  - The complex [Nb(NMe2)2{(NMe2)C=N(t)Bu}{N(2,6-(i)Pr2C6H3)}] reacts with
      trialkylguanidines and undergoes a room temperature C-N bond cleavage of the
      iminocarbamoyl moiety. This reaction affords the guanidinate complexes
      [Nb(NMe2)2{N(2,6-(i)Pr2C6H3)}{(N(i)Pr)2C(NH(i)Pr)}] or [Nb(NMe2)2{N(2,6
      (i)Pr2C6H3)}{(N(i)Pr)2C(NH(n)Bu)}] and free isocyanide. The first crystal
      structure of a niobium iminocarbamoyl complex is reported.

PMID- 23955375
TI  - Surgical anatomy of the posterior liver surface: the retrohepatic lamina as the
      basis for mobilisation of the right liver.
AB  - BACKGROUND: During right hepatectomies, dissection of the bare area is performed
      to obtain mobilisation of the liver. Fifty computed tomography scans of the upper
      abdomen of patients were examined. Specimens of supramesocolic compartment were
      sampled from 10 un-embalmed cadavers. Macrosections were cut for histotopographic
      study. In four cadavers, in situ dissection of the posterior liver surface was
      performed. RESULTS: The hepatophrenic tissue showed a stratigraphic organisation
      resulting from the juxtaposition of thin layer of dense connective tissue
      corresponding to the inferior diaphragmatic fascia (mean thickness is 30 +/- 4
      MUm); variable amount of fibroadipose tissue corresponding to retroperitoneal
      fibroadipose tissue (mean thickness is 34 +/- 8 MUm); two connective layers with
      nets of flat cells forming a fusion fascia, the retrohepatic lamina (mean
      thickness 24 +/- 6 MUm); and layer of connective tissue corresponding to the
      hepatic capsule. The juxta-caval portion of the retrohepatic lamina, connecting
      the right and left sides of the caval groove, forms the inferior vena cava
      ligament. During dissection, fluid injection developed a preferential plane
      between the two layers of the retrohepatic lamina, close to the hepatic surface,
      and no major or minor vessels were ever found along this plane. CONCLUSION:
      During right hepatectomy, to reduce the risk of dissemination of tumour cells,
      the dissection plane should be performed between the two layers of the
      retrohepatic lamina.

PMID- 23955376
TI  - Social networks and support in first-episode psychosis: exploring the role of
      loneliness and anxiety.
AB  - PURPOSE: To investigate social support and network features in people with first
      episode psychosis, and to examine anxiety as a possible mediator between
      loneliness and a rating of paranoia. METHOD: Thirty-eight people with first
      episode psychosis were recruited for a cross-sectional study. Self-report
      questionnaires and structured interviews assessed symptoms, functioning, and
      qualitative social network and support features. A mood-induction task involved
      watching anxiety-inducing pictures on a computer screen. Visual analogue scales
      assessed changes in paranoia, anxiety and loneliness and a mediation analysis was
      conducted. RESULTS: One-third of the sample (34%) had no confidant [95% CI (18.4,
      50.0%)]. The average number of weekly contacts was 3.9, with 2.6 lonely days.
      Poor perceived social support, loneliness and the absence of a confidant were
      strongly associated with psychosis and depressive symptoms (0.35 < rs < 0.60).
      The association between loneliness and paranoia was mediated through anxiety (ab
      = 0.43, z = 3.5; p < 0.001). CONCLUSIONS: Even at first episode, a large
      proportion of people with psychosis have poor perceived support, no confidant and
      report several lonely days a week. Patients without a confidant appear to be more
      susceptible to feeling lonely and anxious. Anxiety may be one pathway through
      which loneliness affects psychosis. Interventions which focus on this are
      indicated.

PMID- 23955377
TI  - Mycotoxigenic fungi and mycotoxins associated with stored maize from different
      regions of Lesotho.
AB  - Samples of stored maize from villages located in five different agroecological
      zones (southern lowlands, northern lowlands, Senqu river valley, foothills and
      mountains) of Lesotho were collected in 2009/10 and 2010/11 and assessed for
      contamination with toxigenic fungi. The water activity of all samples collected
      during the two seasons was <0.70. The total fungal populations of the maize from
      different regions in the two seasons was not significantly different (p > 0.05).
      Fusarium verticillioides, F. proliferatum and F. subglutinans predominated in
      different regions in both seasons based on molecular analyses. In the 2009/10
      season, the isolates of these species all produced FB1, while in the 2010/11
      season, very few produced FB1. A. flavus isolates (2009/10) were recovered from
      mountains and Senqu river valley samples while the 2010/11 isolates were
      predominantly from the foothills and northern lowlands. The mountain isolates of
      Aspergillus section Flavi produced the highest levels of AFB1 (20 mg kg(-1)).
      Aspergillus parasiticus was only isolated from the foothills, Senqu river valley
      and southern lowlands samples, and the AFB1 levels produced ranged from 'none
      detected' to 3.5 mg kg(-1). The Aspergillus ochraceous isolates were least
      frequently encountered in both seasons. In the 2009/10 season, the isolates from
      the northern lowlands produced ochratoxin A (OTA) in culture. No isolates of A.
      niger from different regions in both seasons produced any OTA. Multi-mycotoxin
      analyses of the maize samples were done for a range of mycotoxins. At least one
      sample from each region in both seasons was FB1-positive. FB1 levels for 2010/11
      samples (7-936 MUg kg(-1)) were higher than in the 2009/10 season (2-3 MUg kg(
      1)). In both seasons, the mountains registered the highest levels of FB1.
      Deoxynivalenol (DON) was recovered from all the samples analysed, with the
      highest mean contamination of 1,469 MUg kg(-1) in samples from the northern
      lowlands. Moniliformin (MON) was detected from all agroecological zones in the
      two seasons (5-320 MUg kg(-1) in 2009/10; 15-1,205 MUg kg(-1) in 2010/11).
      Emerging toxins such as fusaproliferin (FUS) and beauvericin (BEA) were also
      detected. OTA was not detected in any of the samples analysed. Only one 2009/10
      sample in the Senqu river valley was positive for AFB1. This is the first report
      on toxigenic fungi and multi-mycotoxin contamination of maize samples from
      subsistence farmers' stores in different agroecological zones of Lesotho. 

PMID- 23955378
TI  - Effectiveness of one dose of mumps vaccine against clinically diagnosed mumps in
      Guangzhou, China, 2006-2012.
AB  - Although mumps-containing vaccines were introduced in China in 1990s, mumps
      continues to be a public health concern due to the lack of decline in reported
      mumps cases. To assess the mumps vaccine effectiveness (VE) in Guangzhou, China,
      we performed a 1:1 matched case-control study. Among children in Guangzhou aged 8
      mo to 12 y during 2006 to 2012, we matched one healthy child to each child with
      clinically diagnosed mumps. Cases with clinically diagnosed mumps were identified
      from surveillance sites system and healthy controls were randomly sampled from
      the Children's Expanded Programmed Immunization Administrative Computerized
      System in Guangzhou. Conditional logistic regression was used to calculate VE. We
      analyzed the vaccination information for 1983 mumps case subjects and 1983
      matched controls and found that the overall VE for 1 dose of mumps vaccine,
      irrespective of the manufacture, was 53.6% (95% confidence interval [CI], 41.0
      63.5%) to children aged 8 mo to 12 y. This post-marketing mumps VE study found
      that immunization with one dose of the mumps vaccine confers partial protection
      against mumps disease. Evaluation of the VE for the current mumps vaccines,
      introduction of a second dose of mumps vaccine, and assessment of modifications
      to childhood immunization schedules is essential. 

PMID- 23955379
TI  - Longitudinal study of correlates of modern contraceptive use and impact of HIV
      care programmes among HIV concordant and serodiscordant couples in Rakai, Uganda.
AB  - OBJECTIVE: To assess trends and determinants of family planning use and impact of
      HIV serostatus among couples. METHODS: Couples' data were retrospectively linked
      from cohort surveys in Rakai, Uganda between 1999 and 2011, and were classified
      by HIV status as concordant (M+F+/M-F-) or serodiscordant (M-F+/M+F-). HIV care
      (HIVC) was grouped into three periods, pre-antiretroviral therapy (pre-HIVC)
      (<2004), HIVC roll-out (2005-2007) and HIVC scale-up (>= 2008). Trends in couple
      contraceptive use were assessed by chi-square test (chi(2)) for trend, and
      multinomial logistic regression was used to estimate adjusted odds ratios (ORs)
      of predictors of contraceptive use. RESULTS: A total of 6139 couples contributed
      13,709 observations. Hormonal contraception (HC) use increased over time from
      22.9% to 33.9%, p<0.001), with significant increases among M-F- (23.2% to 34.8%,
      p<0.0001) and M+F+ (20.8% to 32.2%, p=0.0005), but not serodiscordant couples.
      Condom use significantly increased among M+F+ (30.3% to 48.0%, p<0.001) and
      serodiscordant couples (24.2% to 48.7%, p<0.001), but not among M-F- couples.
      Dual use of HC and condoms increased over time, irrespective of HIV status.
      Factors associated with increases in contraceptive use were: higher education, co
      resident children, male non-marital relationship and scaled-up HIVC phase.
      Enrollment into HIVC was associated with increased HC and condom use among HIV+
      concordant [adjusted OR (adjOR)=3.03; 95% confidence interval (CI) 1.69-5.44 and
      adjOR=4.46, 95% CI 2.53-7.86, respectively], and serodiscordant couples
      (adjOR=2.21; 95% CI 1.25-3.92 and adjOR=4.75; 95% CI 2.89-7.82, respectively).
      CONCLUSIONS: Use of modern contraception and dual method use increased over time,
      particularly after enrollment into HIVC. Integration of HIV and reproductive
      health services is critical for prevention of unwanted pregnancies and HIV
      infection.

PMID- 23955380
TI  - Mercuric chloride-induced gastrin/cholecystokinin 8 immunoreactivity in the
      central nervous system of the terrestrial slug Semperula maculata: an
      immunohistochemical study.
AB  - We measured the immunoreactivity of the neuropeptide gastrin cholecystokinin 8
      (gastrin/CCK 8) in neurons of the terrestrial slug Semperula maculata following
      acute treatment with mercuric chloride (HgCl2). The distribution of gastrin/CCK 8
      was analyzed in neurons of different regions, specifically from cerebral ganglia
      (procerebrum (pro-c), mesocerebrum (meso-c) and metacerebrum (meta-c). In the
      control group, neurons of pedal, pleural, parietal and visceral ganglia showed
      positive immunoreactivity using vertebrate antiserum against gastrin/CCK 8.
      Gastrin/CCK 8 immunoreactivity was also seen in the fibers and neuropil region of
      all ganglia. In the cerebral ganglion, 10, 12 and 8 % of the neurons from pro-c,
      meso-c and meta-c, respectively, were stained with the antibody. The
      immunostaining was increased in neurons (giant, large, medium and small) after
      HgCl2 treatment. The treatment greatly increased the mucin content within the
      neurons. Exposure to HgCl2 enhanced gastrin immunoreactivity in the neurons and
      this increased with time. Results are discussed in the context of neuropathology
      in cerebral ganglia associated with the feeding behavior of Semperula maculata. 

PMID- 23955381
TI  - Methoxistasis: integrating the roles of homocysteine and folic acid in
      cardiovascular pathobiology.
AB  - Over the last four decades, abnormalities in the methionine-homocysteine cycle
      and associated folate metabolism have garnered great interest due to the reported
      link between hyperhomocysteinemia and human pathology, especially
      atherothrombotic cardiovascular disease. However, clinical trials of B-vitamin
      supplementation including high doses of folic acid have not demonstrated any
      benefit in preventing or treating cardiovascular disease. In addition to the fact
      that these clinical trials may have been shorter in duration than appropriate for
      modulating chronic disease states, it is likely that reduction of the blood
      homocysteine level may be an oversimplified approach to a complex biologic
      perturbation. The methionine-homocysteine cycle and folate metabolism regulate
      redox and methylation reactions and are, in turn, regulated by redox and
      methylation status. Under normal conditions, a normal redox-methylation balance,
      or "methoxistasis", exists, coordinated by the methionine-homocysteine cycle. An
      abnormal homocysteine level seen in pathologic states may reflect a disturbance
      of methoxistasis. We propose that future research should be targeted at
      estimating the deviation from methoxistasis and how best to restore it. This
      approach could lead to significant advances in preventing and treating
      cardiovascular diseases, including heart failure. 

PMID- 23955382
TI  - A comparison of retinyl palmitate and red palm oil beta-carotene as strategies to
      address Vitamin A deficiency.
AB  - Vitamin A deficiency continues to be an international public health problem with
      several important health consequences including blindness and overall increased
      rates of morbidity and mortality. To address this widespread issue, a series of
      strategies have been put into place from dietary diversification to
      supplementation and fortification programs. Retinyl palmitate has been used
      successfully for decades as a supplement as well as a way to fortify numerous
      foods, including vegetable oil, rice, monosodium glutamate, cereal flours and
      sugar. Recently, there has been rising interest in using a natural source of
      carotenoids, beta-carotene from red palm oil (RPO), for fortification. Although
      RPO interventions have also been shown to effectively prevent Vitamin A
      deficiency, there are numerous challenges in using beta-carotene from RPO as a
      fortification technique. beta-Carotene can induce significant changes in
      appearance and taste of the fortified product. Moreover, costs of fortifying with
      beta-carotene are higher than with retinyl palmitate. Therefore, RPO should only
      be used as a source of Vitamin A if it is produced and used in its crude form and
      regularly consumed without frying. Furthermore, refined RPO should be fortified
      with retinyl palmitate, not beta-carotene, to ensure that there is adequate
      Vitamin A content. 

PMID- 23955383
TI  - A lifecourse approach to health development: implications for the maternal and
      child health research agenda.
AB  - Lifecourse-informed models of health fundamentally challenge simple biomedical
      models, introducing new ways of thinking about how diseases develop. This paper
      considers the broad implications of lifecourse theory for the maternal and child
      health (MCH) research agenda. The Lifecourse Health Development model provides an
      organizing framework for a synthesis of the existing literature on lifecourse
      health and identification of gaps in knowledge. Priority areas identified for MCH
      research in order to close these knowledge gaps include: epigenetic mechanisms
      and their potential mutability; peri-conception as a critical and sensitive
      period for environmental exposures; maternal health prior to pregnancy; the role
      of the placenta as an important regulator of the intra-uterine environment; and
      ways to strengthen early mother-child interactions. Addressing knowledge gaps
      will require an emphasis on longitudinal rather than cross-sectional studies,
      long-term (lifetime) rather than short-term perspectives, datasets that include
      socio-demographic, biologic and genetic data on the same subjects rather than
      discipline-specific studies, measurement and study of positive health as well as
      disease states, and study of multi-rather than single generational cohorts.
      Adoption of a lifecourse-informed MCH research agenda requires a shift in focus
      from single cause-single disease epidemiologic inquiry to one that addresses
      multiple causes and outcomes. Investigators need additional training in effective
      interdisciplinary collaboration, advanced research methodology and higher-level
      statistical modeling. Advancing a life course health development research agenda
      in MCH will be foundational to the nation's long-term health.

PMID- 23955384
TI  - Environmental risks and children's health: what can PRAMS tell us?
AB  - Environmental exposures during pregnancy have a lasting impact on children's
      health. We combined environmental and maternal risk factor survey data to inform
      efforts to protect children's health. We made recommendations for future use of
      such data. A modified version of the Pregnancy Risk Assessment Monitoring System
      (PRAMS) mail survey was conducted based on weighted sampling design with low
      income and non-low income women in Monroe County, NY (1,022 respondents). A
      series of environmental questions were included in the questionnaire. Data were
      analyzed using Chi square tests and Poisson loglinear regression model to
      identify patterns in environmental health risk and sociodemographic
      characteristics. We identified women who rented their homes, had lower incomes,
      and lived in inner city zip codes as "high environmental health risk" (HEHR).
      HEHR respondents were more likely to report that a health care provider talked
      with them about lead and on average reported more behaviors to protect their
      children from lead poisoning. Combining environmental and perinatal risk factor
      data could yield important recommendations for medical practice, health
      education, and policy development. However, at present PRAMS gathers only limited
      and inconsistent environmental data. We found that existing PRAMS environmental
      questions are insufficient. Further work is needed to develop updated and more
      comprehensive environmental health survey questions and implement them
      consistently across the country. 

PMID- 23955385
TI  - Measuring the severity of prescribing errors: a systematic review.
AB  - BACKGROUND: Prescribing errors are common. It has been suggested that the
      severity as well as the frequency of errors should be assessed when measuring
      prescribing error rates. This would provide more clinically relevant information,
      and allow more complete evaluation of the effectiveness of interventions designed
      to reduce errors. OBJECTIVE: The objective of this systematic review was to
      describe the tools used to assess prescribing error severity in studies reporting
      hospital prescribing error rates. DATA SOURCES: The following databases were
      searched: MEDLINE, EMBASE, International Pharmaceutical Abstracts, and CINAHL
      (January 1985-January 2013). STUDY SELECTION: We included studies that reported
      the detection and rate of prescribing errors in prescriptions for adult and/or
      pediatric hospital inpatients, or elaborated on the properties of severity
      assessment tools used by these studies. Studies not published in English, or that
      evaluated errors for only one disease or drug class, one route of administration,
      or one type of prescribing error, were excluded, as were letters and conference
      abstracts. One reviewer screened all abstracts and obtained complete articles. A
      second reviewer assessed 10 % of all abstracts and complete articles to check
      reliability of the screening process. APPRAISAL: Tools were appraised for country
      and method of development, whether the tool assessed actual or potential harm,
      levels of severity assessed, and results of any validity and reliability studies.
      RESULTS: Fifty-seven percent of 107 studies measuring prescribing error rates
      included an assessment of severity. Forty tools were identified that assessed
      severity, only two of which had acceptable reliability and validity. In general,
      little information was given on the method of development or ease of use of the
      tools, although one tool required four reviewers and was thus potentially time
      consuming. LIMITATIONS: The review was limited to studies written in English. One
      of the review authors was also the author of one of the tools, giving a potential
      source of bias. CONCLUSION: A wide range of severity assessment tools are used in
      the literature. Developing a basis of comparison between tools would potentially
      be helpful in comparing findings across studies. There is a potential need to
      establish a less time-consuming method of measuring severity of prescribing
      error, with acceptable international reliability and validity.

PMID- 23955387
TI  - On the centrality of vertices of molecular graphs.
AB  - For acyclic systems the center of a graph has been known to be either a single
      vertex of two adjacent vertices, that is, an edge. It has not been quite clear
      how to extend the concept of graph center to polycyclic systems. Several
      approaches to the graph center of molecular graphs of polycyclic graphs have been
      proposed in the literature. In most cases alternative approaches, however, while
      being apparently equally plausible, gave the same results for many molecules, but
      occasionally they differ in their characterization of molecular center. In order
      to reduce the number of vertices that would qualify as forming the center of the
      graph, a hierarchy of rules have been considered in the search for graph centers.
      We reconsidered the problem of "the center of a graph" by using a novel concept
      of graph theory, the vertex "weights," defined by counting the number of pairs of
      vertices at the same distance from the vertex considered. This approach gives
      often the same results for graph centers of acyclic graphs as the standard
      definition of graph center based on vertex eccentricities. However, in some cases
      when two nonequivalent vertices have been found as graph center, the novel
      approach can discriminate between the two. The same approach applies to cyclic
      graphs without additional rules to locate the vertex or vertices forming the
      center of polycyclic graphs, vertices referred to as central vertices of a graph.
      In addition, the novel vertex "weights," in the case of acyclic, cyclic, and
      polycyclic graphs can be interpreted as vertex centralities, a measure for how
      close or distant vertices are from the center or central vertices of the graph.
      Besides illustrating the centralities of a number of smaller polycyclic graphs,
      we also report on several acyclic graphs showing the same centrality values of
      their vertices.

PMID- 23955386
TI  - Is colonoscopic screening necessary for patients with gastric adenoma or cancer?
AB  - BACKGROUND: Since colorectal adenoma or cancer is commonly associated with
      gastric adenoma or cancer, early colorectal adenoma detection can affect the
      survival of gastric adenoma or cancer patients. AIMS: The purpose here was to
      investigate the colorectal adenoma or cancer prevalence and evaluate the
      necessity for screening colonoscopy in gastric adenoma or cancer patients.
      PATIENTS AND METHODS: From September 2005 through August 2010, 857 patients
      younger than 70 years who had gastric adenoma or cancer were enrolled. Healthy
      age- and sex-matched controls were selected from the general screening
      population. The prevalence and risk of colorectal adenoma or cancer were compared
      between the participants and the controls. RESULTS: Data from 416 patients in the
      gastric neoplasm group (123 with gastric adenoma and 293 with gastric cancer) and
      416 healthy control group participants were included in the statistical analysis.
      The presence of gastric adenoma or cancer was an independent risk factor for
      colorectal neoplasm (OR = 1.348, 95 % CI = 1.001-1.815). Patients with diffuse
      type gastric cancer had a lower prevalence of colorectal adenoma or cancer than
      those with gastric adenoma or intestinal type cancer. In gastric cancer patients
      younger than 50 years, intestinal type histology was significantly associated
      with colorectal adenoma or cancer (OR = 3.838, 95 % CI = 1.077-13.677).
      CONCLUSIONS: The colorectal adenoma or cancer risk was significantly increased in
      patients with gastric adenoma or cancer. Therefore, screening colonoscopy should
      be considered for gastric adenoma or cancer patients including young patients, in
      the case of intestinal type gastric cancer.

PMID- 23955388
TI  - Hbo1 is a cyclin E/CDK2 substrate that enriches breast cancer stem-like cells.
AB  - Expression of cyclin E proteolytic cleavage products, low-molecular weight cyclin
      E (LMW-E), is associated with poor clinical outcome in patients with breast
      cancer and it enhances tumorigenecity in mouse models. Here we report that LMW-E
      expression in human mammary epithelial cells induces an epithelial-to-mesenchymal
      transition phenotype, increases the CD44(hi)/CD24(lo) population, enhances
      mammosphere formation, and upregulates aldehyde dehydrogenase expression and
      activity. We also report that breast tumors expressing LMW-E have a higher
      proportion of CD44(hi)/CD24(lo) tumor cells as compared with tumors expressing
      only full-length cyclin E. In order to explore how LMW-E enriches cancer stem
      cells in breast tumors, we conducted a protein microarray analysis that
      identified the histone acetyltransferase (HAT) Hbo1 as a novel cyclin E/CDK2
      substrate. The LMW-E/CDK2 complex phosphorylated Hbo1 at T88 without affecting
      its HAT activity. When coexpressed with LMW-E/CDK2, wild-type Hbo1 promoted
      enrichment of cancer stem-like cells (CSC), whereas the T88 Hbo1 mutant reversed
      the CSC phenotype. Finally, doxorubicin and salinomycin (a CSC-selective
      cytotoxic agent) synergized to kill cells expressing LMW-E, but not full-length
      cyclin E. Collectively, our results suggest that the heightened oncogenecity of
      LMW-E relates to its ability to promote CSC properties, supporting the design of
      therapeutic strategies to target this unique function.

PMID- 23955389
TI  - Adenomatous polyps are driven by microbe-instigated focal inflammation and are
      controlled by IL-10-producing T cells.
AB  - Interleukin (IL)-10 is elevated in cancer and is thought to contribute to immune
      tolerance and tumor growth. Defying these expectations, the adoptive transfer of
      IL-10-expressing T cells to mice with polyposis attenuates microbial-induced
      inflammation and suppresses polyposis. To gain better insights into how IL-10
      impacts polyposis, we genetically ablated IL-10 in T cells in APC(Delta468) mice
      and compared the effects of treatment with broad-spectrum antibiotics. We found
      that T cells and regulatory T cells (Treg) were a major cellular source of IL-10
      in both the healthy and polyp-bearing colon. Notably, T cell-specific ablation of
      IL-10 produced pathologies that were identical to mice with a systemic deficiency
      in IL-10, in both cases increasing the numbers and growth of colon polyps.
      Eosinophils were found to densely infiltrate colon polyps, which were enriched
      similarly for microbiota associated previously with colon cancer. In mice
      receiving broad-spectrum antibiotics, we observed reductions in microbiota,
      inflammation, and polyposis. Together, our findings establish that colon
      polyposis is driven by high densities of microbes that accumulate within polyps
      and trigger local inflammatory responses. Inflammation, local microbe densities,
      and polyp growth are suppressed by IL-10 derived specifically from T cells and
      Tregs.

PMID- 23955390
TI  - Formalizing an integrative, multidisciplinary cancer therapy discovery workflow.
AB  - Although many clinicians and researchers work to understand cancer, there has
      been limited success to effectively combine forces and collaborate over time,
      distance, data, and budget constraints. Here we present a workflow template for
      multidisciplinary cancer therapy that was developed during the 2nd Annual
      Workshop on Cancer Systems Biology sponsored by Tufts University, Boston,
      Massachusetts, in July 2012. The template was applied to the development of a
      metronomic therapy backbone for neuroblastoma. Three primary groups were
      identified: clinicians, biologists, and quantitative scientists (mathematicians,
      computer scientists, and engineers). The workflow described their integrative
      interactions; parallel or sequential processes; data sources and computational
      tools at different stages as well as the iterative nature of therapeutic
      development from clinical observations to in vitro, in vivo, and clinical trials.
      We found that theoreticians in dialog with experimentalists could develop
      calibrated and parameterized predictive models that inform and formalize sets of
      testable hypotheses, thus speeding up discovery and validation while reducing
      laboratory resources and costs. The developed template outlines an
      interdisciplinary collaboration workflow designed to systematically investigate
      the mechanistic underpinnings of a new therapy and validate that therapy to
      advance development and clinical acceptance.

PMID- 23955391
TI  - Anticonvulsant activity of 2-(substituted-imino)thiazolidin-4-ones.
AB  - A novel series of 2-(substituted-imino)thiazolidin-4-ones were synthesized and
      evaluated for anticonvulsant activity using the maximal electroshock seizure
      (MES) and subcutaneous pentylenetetrazole (Sc-PTZ) assays and their neurotoxicity
      was measured by the rotarod test. The results of these tests demonstrated that 2
      (4-(pentyloxy)phenylimino)thiazolidin-4-one (5d) was the most potent
      anticonvulsant, with ED50 value of 18.5 mg/kg and 15.3 mg/kg in the MES and Sc
      PTZ tests, and protective index (PI=TD50/ED50) values of 10.6 and 12.8
      respectively. 5d was much safer than a reference drug Carbamazepine.

PMID- 23955392
TI  - Attenuation-corrected fluorescence extraction for image-guided surgery in spatial
      frequency domain.
AB  - A new approach to retrieve the attenuation-corrected fluorescence using spatial
      frequency-domain imaging is demonstrated. Both in vitro and ex vivo experiments
      showed the technique can compensate for the fluorescence attenuation from tissue
      absorption and scattering. This approach has potential in molecular image-guided
      surgery.

PMID- 23955393
TI  - Tiny endoscopic optical coherence tomography probe driven by a miniaturized
      hollow ultrasonic motor.
AB  - We present an endoscopic probe for optical coherence tomography (OCT) equipped
      with a miniaturized hollow ultrasonic motor that rotates the objective lens and
      provides an internal channel for the fiber to pass through, enabling 360 deg
      unobstructed circumferential scanning. This probe has an outer diameter of 1.5
      mm, which is ultra-small for motorized probes with an unobstructed view in distal
      scanning endoscopic OCT. Instead of a mirror or prism, a customized aspheric
      right-angle lens is utilized, leading to an enlargement of the numerical aperture
      and thus high transverse resolution. Spectral-domain OCT imaging of bio-tissue
      and a phantom are demonstrated with resolution of 7.5  MUm(axial)*6.6 
      MUm(lateral) and sensitivity of 96 dB.

PMID- 23955394
TI  - Unsuccessful cyclosporine plus prednisolone therapy for autoimmune
      meningoencephalitis in three dogs.
AB  - A 4-year-old female Maltese (case 1), a 9-year-old castrated male shih tzu (case
      2) and 2-year-old female Pomeranian (case 3) presented with neurological signs,
      such as head tilt, ataxia, circling and paresis. The three cases were tentatively
      diagnosed as having meningoencephalitis of unknown etiology based on computed
      tomography scan and cerebrospinal fluid analysis. All patients were managed with
      cyclosporine plus prednisolone therapy. The survival times of the three patients
      were 170, 70 and 21 days, respectively. After the cases died, we performed
      necropsy and histopathological examination for definitive diagnosis. Based on the
      necropsy, histopathological and immunohistochemical examinations, cases 1, 2 and
      3 were definitely diagnosed as having necrotizing meningoencephalitis,
      necrotizing leukoencephalitis and granulomatous meningoencephalitis,
      respectively. This case report demonstrated the clinical findings, brain CT
      characteristics and histopathological and immunohistochemical features of NME,
      NLE and GME in dogs and discussed the reason for the relatively short survival
      times under cyclosporine plus prednisolone therapy. 

PMID- 23955395
TI  - Primary cerebral T-cell lymphoma in a sea otter (enhydra lutris).
AB  - A 10-year-old female sea otter exhibited convulsions, arrhythmia, hyperthermia,
      forced breathing and anorexia and died after a week. Histopathological
      examination revealed neoplastic proliferation of small round cells with scant
      cytoplasm and round or oval nuclei distributed mainly in the thalamus. The
      proliferation of neoplastic cells was observed in the cerebral parenchyma and
      perivascular areas. The neoplastic cells were immunopositive for CD3, but not
      CD20. No neoplastic proliferation of T-cells was found in other organs. Taken
      together, we diagnosed this case as a primary cerebral T-cell lymphoma. To our
      knowledge, this is the first case of primary cerebral T-cell lymphoma in a sea
      otter. 

PMID- 23955396
TI  - Anesthesia with isoflurane and sevoflurane in the crested serpent eagle
      (Spilornis cheela hoya): minimum anesthetic concentration, physiological effects,
      hematocrit, plasma chemistry and behavioral effects.
AB  - The initial goal of this study was to determine the minimum anesthetic
      concentration (MAC) for isoflurane (ISO) and sevoflurane (SEVO) for the crested
      serpent eagle. Next, we compared the anesthetic effects of each on the
      physiological effects, hematocrit, plasma chemistry values and behavior in
      spontaneously breathing captive adult crested serpent eagles. Sixteen eagles were
      randomly allocated to two groups for anesthesia with ISO (n=8) or SEVO (n=8).
      First, we measured the MAC values of ISO and SEVO, and four weeks later, we
      investigated the effect of each on the physiological effects, hematocrit (HCT)
      and plasma chemistry values. The MAC values of ISO and SEVO for crested serpent
      eagles were 1.46 +/- 0.30 and 2.03 +/- 0.32%, respectively. The results revealed
      no significant differences between the two anesthetics in induction time, while
      time of extubation to recovery was significantly shorter with SEVO. A time
      related increase in end-tidal CO2 and decreases in body temperature and
      respiratory rates were observed during anesthesia with each anesthetic. There
      were no significant differences between the effect of the two anesthetics on
      heart rate, hematocrit, plasma chemistry values or respiration, although each
      caused minor respiration depression. We concluded that SEVO is a more effective
      inhalant agent than ISO for use in eagles, showing the most rapidest induction
      and recovery from anesthesia.

PMID- 23955397
TI  - Qualitative and quantitative contrast enhanced ultrasonography of the pancreas
      using bolus injection and continuous infusion methods in normal dogs.
AB  - Quantitative contrast enhanced ultrasound is a major breakthrough for ultrasound
      imaging in recent years. However, contrast enhancement of the pancreas is brief
      with bolus injection. To assess if continuous infusion of Sonazoid((r)) can
      prolong the duration of pancreatic enhancement over bolus injections, eight adult
      dogs received bolus injection and continuous infusion of Sonazoid((r)) on
      separate days. Contrast enhanced ultrasound of the pancreatic parenchyma and
      proximal descending duodenum was performed, and time intensity curves reflecting
      tissue perfusions were generated. Perfusion parameters- time to initial upslope,
      peak time, time to wash-out and peak intensity were calculated and evaluated.
      Fast wash-in to intense peak, followed by rapid wash-out was observed for time
      intensity curves of bolus injection. With continuous infusion, contrast wash-in
      to peak intensity was gradual, followed by long plateau and slow wash-out. Median
      contrast enhancement durations of the pancreas and duodenum were significantly
      prolonged by continuous infusion from 11 sec (range, 10 to 23 sec) and 16 sec
      (range, 3 to 43 sec) at bolus injection to 205 sec (range, 170 to 264 sec,
      P<0.01) and 193 sec (range, 169 to 216 sec, P<0.05), respectively. Median peak
      intensity of the pancreas was 100.9 MPV (range, 80.2 to 124.3 MPV) at bolus
      injection and 77.6 MPV (range, 58.2 to 99.5 MPV, P<0.05) at continuous infusion.
      Prolonged continuous imaging is afforded by continuous infusion of contrast
      agent. Peak intensity of the pancreas was slightly diminished in continuous
      infusion, but offered adequate imaging subjectively. 

PMID- 23955398
TI  - Prevalence of Toxoplasma gondii infection in rabbits of Korea by serological
      tests and nested polymerase chain reaction.
AB  - This study surveyed the Toxoplasma (T.) gondii infection prevalence in the Korean
      rabbit population. Rabbits (n=142) were obtained from two breeding farms in the
      Gongju area, Chungnam Province, and in the Kochang area, Junbuk Province, Korea.
      Of 142 sera samples analyzed by enzyme-linked immunosorbent assay (ELISA), 15
      (10.6%) exhibited T. gondii-specific IgG antibodies, and 1 (0.7%) rabbit harbored
      T. gondii-specific IgM. Female rabbits (9/84; 10.7%) had a similar T. gondii
      prevalence to males (6/58; 10.3%). When stratified by age, rabbits aged >1 year
      had a similar prevalence of T. gondii infection (7/66; 10.6%) to rabbits aged <1
      year (8/76; 10.5%). Immunoblotting detected 6 major antigenic bands corresponding
      to T. gondii-positive sera at 20, 28, 30, 35, 63 and 77 kDa. Nested polymerase
      chain reaction (PCR) of whole-blood samples detected the T. gondii B1 gene in 23
      rabbits (16.2%). All PCR-positive samples corresponded to partial T. gondii B1
      gene sequences with 99% homology to a T. gondii sequence deposited in GenBank
      (accession number EU340874). Female rabbits (13/84; 15.5%) harbored a similar
      prevalence of T. gondii DNA to males (10/58; 17.2%). Rabbits aged >1 year had a
      similar prevalence (12/66; 18.2%) of T. gondii infection to rabbits aged <1 year
      (11/76; 14.5%). No statistically significant differences were observed regarding
      the prevalences of infection according to sex or age using molecular or
      serological tests. This study is the first survey using serological tests and
      nested PCR to analyze the T. gondii prevalence in rabbits in Korea. 

PMID- 23955399
TI  - Important techniques in today's biomedical science research that PhD candidates
      should be exposed to: a perspective from the FASEB journal.
AB  - The need for best evidence has driven researchers into multidisciplinary,
      collaborative approaches which have become mainstay in today's biomedical
      science. The multidisciplinary and collaborative approaches to research in
      research-intensive academic medical centres in the USA and in other countries of
      affluence has brought in significant advancement in knowledge as well as colossal
      progress and financial benefits. Therefore the author speculates that for
      Nigerian and other African PhD graduates in the basic medical sciences to become
      successful researchers, effective peer reviewers, reliable mentors, and
      progressive administrators in research-based academia, they need some exposure to
      multidisciplinary approaches to research during their subject-based training. The
      present report sought to substantiate this need. Thirty three published articles
      in the April 2012 FASEB Journal were studied for the methodologies employed and
      the results showed that the papers utilized an average of nine major biomedical
      science techniques, 9 being the mean, median, and mode showing the global status
      quo of diversity of methodology per scientific paper. The most popular procedures
      and techniques recorded in more than 1/3 of the published articles were: cell
      isolation; cell culture; in vivo or in situ whole animal studies; animal models
      of disease; gene/protein expression, sequencing and cloning; transfection,
      constructs, and genomic interference and silencing; western blotting;
      fluorescence and confocal microscopy; ELISAs and cell-based assays; and ready
      made biotech assay kits. The most popular statistics testing were various forms
      of student's t-tests at 0.05 confidence levels and ANOVAs. The GraphPad Prism
      software was the most frequently used statistic software. 

PMID- 23955400
TI  - Kolaviron, a biflavonoid complex from Garcinia kola seeds, ameliorates ethanol
      induced reproductive toxicity in male wistar rats.
AB  - In previous studies, we established that kolaviron (KV) (a biflavonoid from
      Garcinia kola seeds) elicited anti-oxidative and hepatoprotective effects in
      Wistar rats chronically treated with ethanol. The present study investigates the
      possible ameliorative effect of KV against ethanol-induced reproductive toxicity
      in male Wistar rats. Twenty-eight rats were randomly divided into four groups of
      seven animals each; Group 1 (control) was administered corn oil, group 2 was
      given 45%v/v ethanol at 3g/kg body weight, group 3 received ethanol and KV
      (200mg/kg) simultaneously and group 4 received KV alone. All drugs were given
      daily by oral gavage for 21 consecutive days. Ethanol treatment resulted in a
      significant (p<0.05) decrease in relative weight of testis of the animals. In the
      spermatozoa, ethanol intoxication resulted in 54%, 21% and 38% decreases in
      testicular protein content, sperm motility and count, respectively. In addition,
      ethanol administration enhanced lipid peroxidation (LPO) process assessed by the
      accumulation of malondialdehyde (MDA) in the testis. Precisely, MDA level was
      increased by 121% in the testis of ethanol-treated rats relative to the control.
      Furthermore, levels of testicular glutathione and activities of testicular
      antioxidant enzymes such as superoxide dismutase and catalase were significantly
      (p<0.05) reduced in ethanol-treated rats. Histopathology showed extensive
      degenerative changes in seminiferous tubules and defoliation of spermatocytes in
      testis of ethanol-treated rats. Interestingly, co-administration of KV with
      ethanol led to almost complete inhibition of testicular LPO thereby enhancing
      antioxidant status of the testis. Overall, KV ameliorates ethanol-induced toxic
      assault on testis and improves seminal qualities of the rats. 

PMID- 23955401
TI  - Effects of zinc on male sex hormones and semen quality in rats.
AB  - This study assessed the effects of zinc on male sex hormones and semen quality in
      male albino wistar rats. Forty rats weighing between 150- 210g, grouped into 5 of
      8 rats each, were used for the research that lasted for six weeks. Group I, the
      control group, received normal rat chow and water ad libitum. The four test
      groups II-V, received 20g, 40g, 60g and 80g of zinc sulphate mixed with their rat
      chow respectively in addition to water for six weeks. Blood samples were
      collected and assayed for Luteinizing hormone (LH), follicle stimulating hormone
      (FSH), Prolactin (PL), testosterone (T), progesterone and oestradiol. Semen was
      also analysed for sperm motility, sperm count and morphology. Results showed
      statistically significant decrease in serum levels of follicle stimulating
      hormone (FSH) (p< 0.05) in groups II and IV with mean values of 0.10+/-0.00 and
      1.20+/-0.00 respectively when compared with the control (1.10+/-0.10). The
      results also revealed statistically significant increase in the serum levels of
      testosterone in groups II, III and IV with mean values of 3.60+/-1.40, 4.5+/-0.30
      and 0.80+/-0.70 respectively when compared with the control with a value of
      0.35+/-0.15. The increase in testosterone levels were dose dependent as there
      were consistent increment in groups II and III after which the levels decreased
      with increasing zinc concentrations. There was statistically significant dose
      dependent decrease in sperm motility and morphology in the test groups compared
      with the control (p<0.05). In conclusion, zinc sulphate has some significant
      positive effects on male sex hormones and sperm quality at doses within
      physiological levels but harmful at higher doses. 

PMID- 23955402
TI  - Levels of serum immunoglobulins in apparently healthy children and adults in Port
      Harcourt, Nigeria.
AB  - Serum levels of the immunoglobulins: IgG, IgA and IgM were determined by the
      single radial immunodiffusion technique of Mancini in a total of 122 apparently
      healthy subjects consisting of 43 children (20 males; 23 females) aged 5-12 years
      and 79 adults (39 males; 40 females) aged 18-65 years resident in Port Harcourt,
      southeastern Nigeria. The effects of age and sex on the serum levels of the
      various immunoglobulin types were also determined. The mean values and ranges for
      the various immunoglobulin types are presented for both children and adults.
      Although, female children were found to have significantly lower mean values of
      IgA compared to male children (p<0.05), there were no significant differences in
      the mean values of both IgG and IgM between male and female children involved in
      the present study (p>0.05). However, female adults had significantly higher mean
      values of IgG and significantly lower mean values of IgA compared to male adults
      (p<0.05); suggesting a significant gender difference in the value of both IgG and
      IgA amongst adult subjects. No significant differences were observed in the mean
      values of any of the various types of immunoglobulin between adults and children.
      The present study reports mean values of the various types of immunoglobulin in
      apparently healthy children and adults resident in Port Harcourt, southeastern
      Nigeria. Significant gender differences were observed for some of the
      immunoglobulin types only amongst adults. Our results suggest that these gender
      differences amongst adults were apparently a gradual build-up from childhood. The
      results also confirm suggestions that levels of some immunoglobulin types seen
      amongst African adults may have possibly been attained during childhood. Our
      study could be of value since previous reports in this regard have been
      relatively scanty especially in this part of Nigeria. 

PMID- 23955403
TI  - ABO (H) secretor status of sickle cell disease patients in Zaria, Kaduna State,
      Nigeria.
AB  - Certain individuals secrete ABO blood group antigens in body fluids and
      secretions while others do not. In this study, the presence of water soluble
      agglutinogens in body fluids such as blood, saliva and urine of 64 sickle cell
      disease patients and 75 AA genotype subjects who served as control were taken and
      tested by hem-agglutination inhibition method. Data obtained was expressed in
      percentages. Results revealed that 84.4% sickle cell patients were secretors
      while 15.6% were non secretors. Amongst the control, 97.3% were secretors while
      3.1% were non secretors. 81.2% SS and 3.2% SS+F patients were secretors while
      15.6% SS were non secretors, 68% AA were secretors and 29.3% AS were secretors
      while 2.7% AA were non secretors. The result showed that a non secretor is more
      likely to be an SS than a secretor and Secretor status is influenced by
      hemoglobin genotype. 

PMID- 23955404
TI  - Myocardial oxygen consumption at rest and during submaximal exercise: effects of
      increased adiposity.
AB  - Overweight and obesity are major risk factors for cardiovascular diseases. The
      objective of this study was to determine the effect of increased adiposity on
      myocardial oxygen consumption at rest and during submaximal exercise in young
      adults. The study consisted of 85 young adults (18-22 years) grouped into 3 based
      on their body mass index as normal (NW, n=30), overweight (OW, n=25) and obese
      (OB, n=30). Steady dynamic exercise test equivalent to Grade 2 Bruce protocol was
      carried out on treadmill for 5min. Blood pressure and heart rate were recorded
      before, during 3rd min of exercise, immediately after cessation of exercise and
      during 5th min of recovery. MVO2 was measured by the Rate Pressure Product (RPP)
      calculated as product of heart rate and systolic blood pressure. Statistical
      analysis was done using ANOVA and regression analysis. The mean resting RPP was
      significantly higher in overweight and obese groups when compared with the normal
      weight group (p<0.05). There was significant increase in RPP changes to exercise
      [mean difference in NW-8270.93 bpm.mmHg (99.61%), OW-10593.12 bpm.mmHg (118.39%)
      and OB-10897.33 bpm.mmHg (118.10%), p< 0.05] and the value did not return to
      baseline after 5 mins of recovery in study groups (p< 0.05). BMI and Waist
      stature ratio were the most important independent parameters in prediction of
      RPP. The study shows that overweight and obese young adults have elevated resting
      RPP and much higher RPP response to exercise indicating increased (MVO2) at rest
      and during exercise suggesting higher hemodynamic stress to the heart.

PMID- 23955405
TI  - Serum uric acid levels among Nigerians with essential hypertension.
AB  - There is an ongoing debate on the role of serum uric acid as an independent risk
      factor for hypertension and renal disease. This study determined the serum uric
      acid levels of Nigerians with essential hypertension and also evaluated the
      association between serum uric acid levels and blood pressure of these patients.
      A retrospective case-control study of three hundred and fifty one patients with
      essential hypertension seen at the hypertension clinic of Aminu Kano Teaching
      Hospital, Kano between January 2004 and December 2008. The control group
      comprised of one hundred apparently healthy non hypertensive subjects. The
      clinical characteristics including blood pressure measurement, serum uric acid,
      urea, creatinine, lipid profile and glucose were evaluated.The mean systolic and
      diastolic blood pressures of the male patients were 156mmHg and 101mmHg
      respectively, while those of the male controls were 120 +/- 6.0 and 80 +/- 5
      respectively. The mean serum uric acid, fasting blood glucose, urea and
      creatinine were 483umol/L, 5.7mmol/L,6.61mmol/L, 93umol/l respectively compared
      to those of the male controls which were 326 +/-10MUmol/l, 5.0+/- 0.5mmol/l,
      4.2+/- 0.12mmol/l, 5.16mmol/l +/- 0.12 and 69+/-2.71MUmol/l respectively. The
      mean systolic and diastolic blood pressures of the female patients were 158mmHg
      and 101mmHg, while those of the female controls were 101+/-2 and 62+/-9
      respectively. The mean serum uric acid, fasting blood glucose, urea and
      creatinine of the female patients were 434umol/L, 5.3mmol/L 6.20mmol/L, and
      88umol/L respectively while those for the female controls were 290+/-9MUmol/l,
      4.8+/-0.5mmol/l, 5.02+/-0.28 mmol/l, 62+/-0.36MUmol/l respectively.
      Hyperuricaemia was observed in 59.3% of the male study patients and 62% of the
      female study patients. Serum uric acid correlated positively with both systolic
      blood pressure (r=0.192, p<0.001) and diastolic blood pressure (r=0.216;
      p<0.001). Hyperuricaemia is common among Nigerian patients with essential
      hypertension and there is an association between serum uric acid level and blood
      pressure. Further studies on the pathophysiologic significance of hyperuricaemia
      in these patients are recommended. 

PMID- 23955406
TI  - L-arginine increases nitric oxide and attenuates pressor and heart rate responses
      to change in posture in sickle cell anemia subjects.
AB  - Pressor and heart rate changes following change in posture without or with L
      arginine supplementation (1g/day for 6 weeks) were studied in 28 sickle cell
      anemia (SCA) and 32 non-sickle cell anemia (NSCA) subjects. Change in posture
      increased HR (p<0.01), RPP (p<0.05) in both groups of subjects, MABP (p<0.05) in
      SCAS but reduced MABP (p<0.01) in NSCAS and PP (p<0.01) in SCAS. L-Arginine
      supplementation increased plasma L-Arginine concentration ([R]) in both groups of
      subjects (p<0.001 in each group) and serum nitric oxide metabolites concentration
      ([NOx]) (p<0.01 in each group). Change (Delta) [R] correlated positively with
      Delta [NOx] in both groups (+ 0.7 in each group). L-Arginine supplementation
      caused greater reduction of MABP (p<0.001) in NSCAS than in SCAS. However,
      reduction in HR was greater (p<0.001) in SCAS than in NSCAS. After
      supplementation, MABP and PP responses to change in posture were attenuated in
      the two groups. However, while HR and RPP responses in SCAS were attenuated, the
      same responses were enhanced in NSCAS by change in posture after supplementation.
      In conclusion, study shows that oral, low dose, chronic supplementation with L
      arginine increased NO availability and attenuated pressor and heart rate
      responses to change in posture in sickle cell anemia subjects. 

PMID- 23955407
TI  - Evaluation of tribromoethanol, tribromoethanol-buprenorphine and ketamine
      xylazine combinations for anaesthesia in Sprague-Dawley rats undergoing
      ovariectomy.
AB  - Effect of premedication with buprenorphine (BP) on efficacy and safety of
      tribromoethanol (TBE) - induced anaesthesia was evaluated and compared with
      anaesthesia induced by ketamine (K) and xylazine (X) combination in rats
      undergoing ovariectomy. Fifteen Sprague -Dawley rats (mean weight 246.5 +/-
      13.1g) were randomly divided into three groups. Group (TBE) received
      tribromoethanol solution (250mg/kg). Group (TBE+BP) was premedicated with BP
      (0.02mg/kg) and 30 minutes later with TBE (250mg/kg). Group KX was anaesthetized
      with mixture of K (43.5mg/kg) and X (6.5mg/kg). All injections were administered
      intraperitoneally. Anaesthetic parameters determined were onset of anaesthesia
      (OAN), duration of antinociception (DAN), duration of sleep (DSP) and recovery
      time (RCT). Rectal temperatures (RT) and respiratory rates (RR) were recorded
      immediately after loss of righting reflex and at ten minute interval up to 90
      minute. In addition, rats were monitored for adverse signs up to one week after
      ovariectomy. Anaesthetic indices were compared using Student's t-test, while RR
      and RT were compared using analysis of variance (ANOVA). Two rats in TBE group
      and one rat in TBE+BP group died three days after ovariectomy. Duration of
      antinociception (DAN) was significantly (P= 0.0015) longer in TBE than in KX
      anaesthetized rats but not significantly (P= 0.054) different between TBE and TBE
      BP anaesthetized rats. Also, DSP was significantly (P=0.001) longer in KX
      anaesthetized rats than TBE- anaesthetized rats. Similarly, the DSP was
      significantly (P= 0.013) shorter in TBE group than TBE+ BP anaesthetized rats.
      Both RR and RT decreased significantly (P< 0.0001) with time following
      anaesthesia in all groups. It was concluded that KX mixture provided better
      anaesthesia than TBE and TBE+BP, and addition of BP to TBE did not have any
      beneficial effect. 

PMID- 23955408
TI  - Visual indices of motor vehicle drivers in relation to road safety in Nigeria.
AB  - This study assessed the visual profile of motor vehicle drivers in Owerri,
      Nigeria and to analyse the relationship between the various aspects of visual
      function in relation to road safety. A cross-sectional descriptive study of 150
      commercial vehicles drivers and 130 private vehicles drivers was conducted
      between November 2005 and February 2006. Data were obtained using structured
      interviewer administered questionnaires and clinical examination was done.
      Standards procedures were used to determine visual indices. Data from the better
      eye (eye with a better visual acuity according to international and national
      standards) were reported, except in the analysis of near vision of the
      respondents. Twenty percent of the study group had normal visual acuity of >=6/6
      compared with 46.2% in the control group. The tonometric value in 88.0% and 93.1%
      of study and control groups respectively was less than 24mmHg. Both groups
      (96.8%) had normal confrontation visual field while 95.3% of study group and
      97.7% of control group had normal colour vision. The most prevailing eye
      conditions that may reduce visual acuity were pterygium (51.3% in study group and
      13.8% in the control group), retinopathy (16.7% of study group and 6.2% of
      control group) and glaucoma (12.0% and 6.9% of study and control groups
      respectively). Nineteen percent of the study group had regular eye examination
      compared with 38.5% in the control group. Alcohol consumption was 64.7% in the
      study group and 32.3% in the control group. Most of the commercial motor drivers
      in Owerri, Nigeria did not meet the Federal Road Safety Commission visual acuity
      standard for commercial motor drivers. Visual impairments and poor visibility are
      strongly associated with RTA among Nigerian motor vehicle drivers. Visual acuity
      and visual health care were poor among commercial motor drivers. There is need
      for renewed efforts to enforce a compulsory periodic visual examination for
      drivers, and to ensure that visual requirements for driving are met. 

PMID- 23955409
TI  - Changes in haematology, plasma biochemistry and erythrocyte osmotic fragility of
      the Nigerian laughing dove (Streptopelia senegalensis) in captivity.
AB  - The haematology, plasma biochemistry and erythrocyte osmotic fragility of the
      Nigerian laughing dove (Streptopelia senegalensis) were studied after 4 and 8
      weeks in captivity. At 8 weeks, there was a normocytic hypochromic anaemia
      characterized by reduced values for packed cell volume (PCV), red blood cell
      count (RBC), haemoglobin (Hb) concentration, mean corpuscular haemoglobin (MCH)
      and mean corpuscular haemoglobin concentration (MCHC), but the mean corpuscular
      volume (MCV) was unaltered compared with the corresponding values at 4 weeks. The
      platelet count, total white blood cell count, heterophil, lymphocyte and monocyte
      counts were also lower at 8 weeks than those of the birds sampled at 4 weeks in
      captivity. There was also a stress induced increased heterophil/lymphocyte ratio
      and the erythrocytes were more fragile in hypotonic solution in birds sampled at
      8 weeks. Plasma aspartate transaminase (AST), alanine aminotransferase (ALT) and
      alkaline phosphate (ALP) increased at 8 weeks, though non-significantly, which
      might have been due to muscle wasting consequent upon decreased muscular
      activities associated with prolonged captivity. The results suggest that
      maintaining wild birds in captivity for a prolonged period could be stressful as
      shown by the heterophil/lymphocytes ratio and reduced erythrocyte osmotic
      resistance, and could lead to decreases in erythrocyte parameters and muscle
      wasting. 

PMID- 23955410
TI  - Maternal blood viscosity and perinatal outcome in steady-state homozygous sickle
      cell disease.
AB  - Homozygous sickle cell disease (HbSS) is a complicating factor in pregnancy
      resulting in perinatal morbidity and mortality. One of the hallmarks of sickle
      cell disease is increased whole blood viscosity. The present study was designed
      to investigate the effect of the maternal blood viscosity on perinatal outcome in
      steady-state homozygous sickle disease in 19 women admitted to the labor ward of
      the University Hospital of the West Indies, Mona. Whole blood viscosity was
      measured with the Wells-Brookfield viscometer at 370C at low (23 sec-1) and high
      (230 sec-1) shear rates. Measurements were done at native hematocrit. Perinatal
      outcome was classified as adverse if there was one or more of the following:
      admission to nursery, birth weight less than 2.5 kg, 5 minute Apgar score less
      than 7, caesarean section for fetal distress, perinatal death or death before
      discharge from nursery. The whole blood viscosity value (mean +/- SD) at low
      shear rate was 2.04 +/- 0.55 mPa.s and 2.96 +/- 0.80 mPa.s at high shear rate.
      The hematocrit was 25.13 +/- 4.18%. The perinatal outcome was good in 10 (53%)
      subjects and adverse in 9 (47%) subjects. There was no statistically significant
      difference in the incidence of adverse perinatal outcome between women with low
      and high blood viscosities in either the low or high shear rates. Similarly, low
      or high hematocrit did not significantly affect the incidence of adverse
      perinatal outcome. This could be attributed to their similarity in the whole
      blood viscosity and hematocrit values. 

PMID- 23955411
TI  - Contributory role of adenosine deaminase in metabolic syndrome.
AB  - Adenosine deaminase (ADA) is an enzyme of purine metabolism commonly associated
      with severe combined immunodeficiency disease and believed to modulate
      bioactivity of insulin. Its contributory role in patients with metabolic syndrome
      (having features such as obesity, insulin resistance, fasting hyperglycaemia,
      lipid abnormalities and hypertension) in South Eastern Nigeria was studied. Body
      mass index (BMI), fasting blood glucose (FBG), Glycated haemoglobin (GHbA1c),
      total cholesterol, HDL-cholesterol, LDL-cholesterol (usually impaired in
      metabolic syndrome) and total serum ADA activity were measured in different
      groups of patients with metabolic syndrome (test subjects) and apparently healthy
      subjects (controls). The test subjects comprised six subgroups made up of the
      following; obese diabetic (N=25), obese non-diabetic (N=25), Non-obese diabetic
      (N=25), patients with hypercholesterolaemia (N=25), LDL-cholesterolaemia (N=25)
      and HDL-cholesterolaemia (N=25). The results showed that the mean values of all
      the parameters studied (BMI, FBG, GHbA1c, total cholesterol, HDL-cholesterol and
      LDL-cholesterol) were higher in the test subjects than their controls. BMI did
      not correlate significantly with FBG, GHbA1c, and ADA in the test and control
      subjects respectively. The mean serum ADA activity in the test subjects of obese
      diabetic, obese non-diabetic and non-obese diabetic subjects was higher than in
      controls (p< 0.001). ADA activity was also higher in the test subjects of
      hypercholesterolaemia, HDL-cholesterolaemia and LDL-cholesterolaemia than in
      control (p< 0.001). ADA activity also correlated positively with
      hypercholesterolemia (r = 0.640; p<0.001), HDL-cholesterolaemia (r = 0.646;
      p<0.001) and LDL-cholesterolaemia (r = 0.932; p<0.001), with the highest
      correlation in the LDL-cholesterolaemia. In conclusion, ADA activity is increased
      significantly in all parameters of metabolic syndrome studied and showed a
      significant correlation with all the three groups of dyslipidaemic subjects
      studied. ADA could therefore be used in daily routine laboratory assessment of
      most metabolic diseases especially in obese and diabetic patients. 

PMID- 23955412
TI  - Sub-acute Toxicity of Aqueous Fruit Pulp Extract of Hunteria umbellata in Albino
      Wistar Rats.
AB  - Hunteria umbellata K. Schum (Apocynaceae) is used in herbal medicine for the
      treatment of diabetes, peptic ulcers, piles, yaws, dysmenorrhea, fevers,
      infertility, and helminthic infections. The present study investigated the in
      vivo sub-acute toxicity of the aqueous fruit pulp extract of Hunteria umbellata
      (H. umbellata). Sub-acute toxicity was evaluated after administering daily oral
      doses of 200, 400 and 800 mg/kg of H. umbellata extract, for 28 days to the rats.
      Anthropometric, biochemical, hematological and histopathological parameters were
      assessed using standard procedures. There were significant reductions (p<0.01) in
      the pattern of weight gain in 200 and 400 mg/kg H. umbellata -treated rats but no
      significant differences in the organ weight index between control and treated
      animals. Hematological and biochemical analysis showed no marked differences in
      any of the parameters examined in either the control or treated groups but there
      was significant (p<0.05) thrombocytosis. Pathologically, neither gross
      abnormalities nor histopathological changes were observed. H. umbellata led to
      activation of the reticulo endothelial tissue of the spleen as evidenced by
      proliferation of the sinus histocytes and activation of the lymphoid aggregates
      in the lungs, indicating activation of the local immune system of the lungs. H.
      umbellata fruit pulp is relatively nontoxic in animals but there is increased
      tendency to cause thrombocytosis on prolonged use. 

PMID- 23955413
TI  - Thirst perception, plasma osmolality and estimated plasma arginine vasopressin
      concentration in dehydrated and oral saline loaded subjects.
AB  - Infusion of hypertonic saline produces an increase in thirst appreciation as well
      as increase in plasma Arginine Vasopressin (AVP) concentration, which may be
      estimated using thirst perception and/or plasma osmolality In this study, we
      examined the changes in thirst perception (TP), plasma osmolality (Posm) and
      plasma arginine vasopressin concentration (PAVP) as well as their relationships
      in dehydrated and oral saline loaded subjects. Forty (40) healthy subjects
      between the ages of 18 and 30 years were divided into 4 groups of 10 subjects (5
      females and 5 males) each. Subjects in group A (dehydrated) were subjected to 18
      hr fluid restriction, while those in B, C, and D orally ingested 7.1 ml/kg of
      0.9%, 1.8% and 2.7% NaCl solutions respectively. TP was rated using the Visual
      Analogue Scale, VAS. Estimation of Posm was done using the standard formula and
      was also calculated from TP. PAVP was calculated from TP and Posm. The changes in
      TP in water restriction and salt loadings were similar in both males and females.
      However, the 2.7% NaCl sodium chloride solution intake induced a greater increase
      in TP than the 18 h fluid restriction. In females there was no significant
      difference between the measured and calculated Posm at 0 min, in groups A and D,
      whereas, values for group B (278.8+/-4.2 vs 292.0+/-2.9 mOsm/kgH2O) and C
      (282.6+/-4.1 vs 295.6+/-2.5 mOsm/kgH2O) differ significantly (p<0.05). At 90 min,
      the calculated Posm was significantly higher than the measured Posm in group D
      (283.6+/-2.1 vs 312.0+/-0.8 mOsm/kgH2O, p<0.05) only. In male subjects, there was
      no significant difference between the measured and calculated Posm in all the
      groups at 0 min, and at 90 min in groups A and B, while the calculated Posm was
      significantly higher (p<0.05) than the measured Posm in groups C (283.0+/-4.6 vs
      302.4+/-3.3 mOsm/kgH2O) and D (275.6+/-4.8 vs 307.2+/-2.6 mOsm/kgH2O). In both
      male and female subjects, there was a significant (p<0.05) and positive
      correlation between TP and measured Posm at 0 min, but not at 90 min. PAVP values
      correlated significantly (p<0.05) with Posm and TP at 90 min only in group A.
      When group A was compared to group B, the changes in Posm were significant
      (p<0.05) in the males at 0 min (298.0+/-1.6 vs 281.0+/-4.4 mOsm/kgH2O), and at 90
      min (303.0+/-1.8 vs 270.6+/-11.0 mOsm/kgH2O), whilst in the females the changes
      were only significant at 90 min (304.4+/-3.5 vs 285.0+/-4.3 mOsm/kgH2O). We can
      reasonably conclude the relationship between TP, Posm and PAVP may not be
      maintained during oral hypertonic saline loading, probably due to body fluid
      changes. 

PMID- 23955414
TI  - Anti-diabetic property of Methanol extract of Musa sapientum leaves and its
      fractions in alloxan-induced diabetic rats.
AB  - Diabetes mellitus is a metabolic disorder resulting from necrosis of beta-cell
      and insulin resistance at the cellular level. Musa sapientum has been shown to
      possess anti-diabetic properties, however, the mechanism of its action is
      unknown. The effect of Methanolic extract of Musa sapientum leaves (MEMSL) and
      its fractions were assessed for in vitro inhibitory activity of alpha-amylase
      enzyme, in vivo hypoglycemic properties and liver glycogen content in alloxan
      induced diabetic rats. Dried plant powder of Musa sapientum was successively
      extracted using n-hexane, ethyl acetate, dichloromethane and methanol
      respectively. The filtrate obtained was evaporated using rotary evaporator and
      the extract was stored at 4 degrees C until use. The methanolic extract obtained
      was further fractionated using column chromatography. In vitro alpha amylase
      inhibitory activity of the methanolic extract at different doses (2.5mg/ml,
      5mg/ml, 10mg/ml, 25mg/ml and 50mg/ml) and column fractions (100ug/ml) were
      assessed and compared with that of acarbose (5mg/ml), a standard oral alpha
      amylase inhibitor. Hypoglycemic activity and liver glycogen content was studied
      using alloxan -induced diabetic male rats treated with MEMSL (250mg/kg and
      500mg/kg), column fractions F2 and F5 (100MUg/kg) for 14 days respectively.
      Results obtained showed a dose -dependent increase in alpha-amylase inhibitory
      activity of the methanolic extract at 5, 10, 25 and 50mg/ml exhibiting 29%, 61%,
      and 72% and 80% inhibitory activities respectively. Column fractions 2 and 5
      showed the highest alpha-amylase inhibitory activity of 79% and 74% respectively.
      The MEMSL at 250mg/kg and 500mg/kg exhibited 66% and 59% hypoglycemic activities
      respectively compared with diabetic controls. Fractions 2 and 5 showed 48% and
      75% reduction in blood glucose level respectively. Liver glycogen in diabetic
      animals treated with MEMSL (250mg/kg and 500mg/kg), F2 and F5 were significantly
      increased (5.5+/-0.5, 5.9+/-0.7, 3.6+/-0.5, 8.0+/-0.4 mg/100gwt. liver) compared
      with Diabetic controls (1.2+/-0.3 mg/100gwt. liver) respectively suggesting an
      increase in glucose storage or reduction in glycogen breakdown. It seems possible
      that the anti-diabetic properties in the leaf extract of Musa sapientum and its
      fractions maybe due to the inhibition of alpha-amylase, increased storage of
      glucose as glycogen in the liver and/or reduced breakdown of liver glycogen
      stores. 

PMID- 23955415
TI  - Effects of Ethanol Leaf Extract of Ficus Glumosa on Fasting blood Glucose and
      Serum Lipid Profile in Diabetic Rats.
AB  - Ficus glumosa, commonly known as the fig tree or "African rock fig" is a plant
      with immense medicinal value used for the management of diabetes for over 2000
      years. The aim of the present study is to determine the hypoglycemic and anti
      lipidemic properties of the ethanolic leaves extract of Ficus glumosa in alloxan
      induced diabetic Wistar rats. Thirty (30) adult male Wister rats weighing (120 -
      220) grams of about 18 to 22 weeks of age were used in the study. The animals
      were assigned into six groups (1-6) of five rats (n=5) each. Group VI served as
      the positive control group receiving 0.9% normal saline (5ml/kg) alone via intra
      peritoneal route (i.p.), Groups I (negative control), II, III, IV and V were
      treated with alloxan and after the induction of hyperglycaemia, received in
      addition via i.p. for 7 days: 0.9% normal saline (5ml/kg) alone, 100mg/kg,
      200mg/kg and 400mg/kg of ethanolic leaves extract of Ficus glumosa respectively
      while Group V received 6lU/kg of short-acting insulin. The determinations of
      blood glucose levels were carried out at intervals of one day for 7 days. Serum
      lipid profile, were done on the 7th day.Premininary phytochemical screening
      revealed the presence of flavonoids,saponin,tannins,cardiac
      glycosides,triterpenes,ceramides and reducing sugars.The LD50 of the extract of
      Ficus glumosa was found to be 2,154mg/kg.The results of the study showed
      that,100mg/kg and 400mg/kg of ethanolic leaves extract of Ficus glumosa
      significantly lowered blood glucose levels and 200mg/kg significantly lowered
      serum lipid profile compared with negative control group.In conclusion, the
      results of the study showed that Ficus glumosa possesses anti-hyperglycaemic and
      anti-lipidemic effect. 

PMID- 23955416
TI  - Non Protease Inhibitor-Based Highly Active Antiretroviral Therapy (HAART)
      improves micromineral status in HIV positive Nigerians.
AB  - Introduction of highly active antiretroviral therapy (HAART) has improved the
      prognosis of human immunodeficiency virus (HIV) infection. The social burden of
      HIV infection in Nigeria is well appreciated, but the consequences of this
      infection and HAART on micro mineral status are unknown in Nigeria. We evaluated
      these effects in Orlu, Imo State, Nigeria. This prospective study involved 51
      adult HIV positive patients (18-56 years). Serum selenium, magnesium and zinc
      were measured using atomic absorption spectrophotometry before and after 6 months
      on HAART. Results are presented as means while comparison of variables was done
      using paired t-tests. P-value < 0.05 was considered significant. Selenium,
      magnesium and zinc levels in the participants before HAART were 0.23+/-0.08
      mmol/L, 104.61+/-24.16 mmol/L and 9.04+/-1.26 mmol/L respectively. Mineral levels
      6 months after HAART were 0.25+/-0.08 mmol/L, 115.57+/-27.98 mmol/L and 9.41+/
      1.23 mmol/L respectively. Selenium and magnesium levels significantly increased
      after 6 months on HAART (p < 0.05) while zinc level did not increase
      significantly (p> 0.05). HAART improved selenium and magnesium status of HIV
      patients but their zinc status remained the same. 

PMID- 23955417
TI  - Attitude of HIV patients to herbal remedy for HIV infection in Nigeria.
AB  - World Health Organisation estimated that about 80% of Africans use herbal
      remedies for illness. Human immunodeficiency virus (HIV) infection which was
      believed to have no cure led many HIV patients to source for alternative or
      complementary therapy. A structured questionnaire was administered to 640 HIV
      patients in selected Nigerian HIV/AIDS clinics from 2009 to 2011 to assess their
      attitudes to the use of herbal remedy. Six hundred and ten (610) of the
      respondents were diagnosed by medical doctor and 6.3% (40) had lived with HIV for
      4 years and above. Twenty (20) respondents had sought for medical therapy after
      diagnosis, 310 applied herbal remedy and 180 of the respondents opted for
      spiritual solutions. Although, majority (73.4%) would denied the use of herbal
      remedy when asked by a medical practitioner, 100 respondents combines herbal
      remedy with HAART and 67.2% of the entire respondents are of the opinion that
      herbal therapy is effective in HIV infection management. 64.1% of the respondents
      wanted herbal remedy as complementary therapy and 54.7% concluded that non
      availability of herbs could stop them from using herbal remedy. This study
      concluded that the use of herbal remedy for HIV infection is high despite advice
      by medical doctors thus there is a need for caution when prescribing orthodox
      medicines that could interfere with hepatic metabolism. 

PMID- 23955418
TI  - Changes in cardiovascular function after venlafaxine but not pregabalin in
      healthy volunteers: a double-blind, placebo-controlled study of orthostatic
      challenge, blood pressure and heart rate.
AB  - It is generally thought that venlafaxine raises blood pressure at higher doses;
      however, some studies have found no effect or a decrease in blood pressure. The
      aim of this study was to evaluate the cardiovascular (CV) effects of 3 weeks of
      dosing with venlafaxine, pregabalin and placebo on young healthy adults. Fifty
      four participants, of mean age 23.1 years (sd 4.68), 29 male, were randomised
      into three parallel groups. Each group received one of the three drugs, dosed
      incrementally over a 3-week period to reach daily doses of 150 mg/day venlafaxine
      and 200 mg/day pregabalin. Blood pressure sphygmomanometer measurements, heart
      rate measurements, and orthostatic challenges recorded continuously beat-to-beat
      were performed weekly over this period and 5 days after treatment cessation.
      Results showed resting systolic blood pressure (SBP) and resting and standing
      diastolic blood pressure (DBP) and heart rate (HR) were significantly raised by
      venlafaxine compared with the pregabalin and placebo groups. SBP drop on standing
      was larger, the resulting overshoot was smaller, and recovery was slower on
      venlafaxine. HR recovery was significantly impaired by venlafaxine. CV changes
      were observed after only 1 week of dosing at 112.5 mg/day. These effects of
      venlafaxine are likely to be due to its action of noradrenergic reuptake
      inhibition.

PMID- 23955419
TI  - IL12B and IL23R gene SNPs in Japanese psoriasis.
AB  - Psoriasis is a common human skin disease whereby abnormal production of
      inflammatory mediators is believed to play an important role in its pathogenesis.
      The IL12B gene, which encodes the shared IL-12p40 subunit in two cytokines, IL-12
      and IL-23, and the IL23R gene, which encodes a subunit of the receptor for IL-23,
      were identified as psoriasis-susceptibility genetic factors in recent candidate
      gene and genome-wide association studies of Chinese and Europeans. Since there
      are significant differences in the incidence of psoriasis between Europeans and
      Japanese suggesting a genetic ethnic effect, we examined the association of IL12B
      and IL23R gene polymorphisms with psoriasis in a cohort of Japanese. In this
      study, we genotyped two SNPs (rs3212227 and rs6887695) in the IL12B gene and one
      SNP (rs11209026) in the IL23R gene using 560 Japanese psoriasis cases and 560
      controls and compared our results with those previously published for Europeans
      and Asians. Our study showed significant associations between psoriasis and both
      IL12B gene SNPs, rs3212227 (odds ratio (OR) = 1.35, P = 4.94E-04) and rs6887695
      (OR = 1.32, P = 2.00E-03), but no significant association between psoriasis and
      the IL23R SNP, rs11209026. Furthermore, a significant haplotype association was
      found for the IL12B gene protective haplotype C-C (OR = 0.71, P = 1.84E-04) in
      Japanese, as previously elucidated in the studies of European ancestry.

PMID- 23955420
TI  - FLOWERING LOCUS C in monocots and the tandem origin of angiosperm-specific MADS
      box genes.
AB  - MADS-domain transcription factors have been shown to act as key repressors or
      activators of the transition to flowering and as master regulators of
      reproductive organ identities. Despite their important roles in plant
      development, the origin of several MADS-box subfamilies has remained enigmatic so
      far. Here we demonstrate, through a combination of genome synteny and
      phylogenetic reconstructions, the origin of three major, apparently angiosperm
      specific MADS-box gene clades: FLOWERING LOCUS C- (FLC-), SQUAMOSA- (SQUA-) and
      SEPALLATA- (SEP-)-like genes. We find that these lineages derive from a single
      ancestral tandem duplication in a common ancestor of extant seed plants. Contrary
      to common belief, we show that FLC-like genes are present in cereals where they
      can also act as floral repressors responsive to prolonged cold or vernalization.
      This opens a new perspective on the translation of findings from Arabidopsis to
      cereal crops, in which vernalization was originally described.

PMID- 23955421
TI  - Fusion and subsidence rate of stand alone anterior lumbar interbody fusion using
      PEEK cage with recombinant human bone morphogenetic protein-2.
AB  - INTRODUCTION: Anterior lumbar interbody fusion (ALIF) is an established treatment
      for structural instability associated with symptomatic disk degeneration (SDD).
      Stand-alone ALIF offers many advantages, however, it may increase the risk of non
      union. Recombinant human bone morphogenetic protein-2 (BMP-2) may enhance fusion
      rate but is associated with postoperative complication. The optimal dose of BMP-2
      remains unclear. This study assessed the fusion and subsidence rates of stand
      alone ALIF using the SynFix-LR interbody cage with 6 ml/level of BMP-2. METHODS:
      Thirty-two ALIF procedures were performed by a single surgeon in 25 patients.
      Twenty-five procedures were performed for SDD without spondylolisthesis (SDD
      group) and seven procedures were performed for SDD with grade-I olisthesis (SDD
      olisthesis group). Patients were followed-up for a mean of 17 +/- 6 months.
      RESULTS: Solid fusion was achieved in 29 cases (90.6 %) within 6 months
      postoperatively. Five cases of implant subsidence were observed (16 %). Four of
      these occurred in the SDD-olisthesis group and one occurred in the SDD group (57
      % vs. 4 % respectively; p = 0.004). Three cases of subsidence failed to fuse and
      required revision. The body mass index of patients with olisthesis who developed
      subsidence was higher than those who did not develop subsidence (29 +/- 2.6 vs.
      22 +/- 6.5 respectively; p = 0.04). No BMP-2 related complications occurred.
      CONCLUSION: The overall fusion rate of stand-alone ALIF using the SynFix-LR
      system with BMP-2 was 90.6 %, comparable with other published series. No BMP-2
      related complication occurred at a dose of 6 mg/level. Degenerative
      spondylolisthesis and obesity seemed to increase the rate of implant subsidence,
      and thus we believe that adding posterior fusion for these cases should be
      considered.

PMID- 23955422
TI  - Phenylethynyl-butyltellurium inhibits the sulfhydryl enzyme Na+, K+ -ATPase: an
      effect dependent on the tellurium atom.
AB  - Organotellurium compounds are known for their toxicological effects. These
      effects may be associated with the chemical structure of these compounds and the
      oxidation state of the tellurium atom. In this context, 2-phenylethynyl
      butyltellurium (PEBT) inhibits the activity of the sulfhydryl enzyme, delta
      aminolevulinate dehydratase. The present study investigated on the importance of
      the tellurium atom in the PEBT ability to oxidize mono- and dithiols of low
      molecular weight and sulfhydryl enzymes in vitro. PEBT, at high micromolar
      concentrations, oxidized dithiothreitol (DTT) and inhibited cerebral Na(+), K(+)
      ATPase activity, but did not alter the lactate dehydrogenase activity. The
      inhibition of cerebral Na(+), K(+)-ATPase activity was completely restored by
      DTT. By contrast, 2-phenylethynyl-butyl, a molecule without the tellurium atom,
      neither oxidized DTT nor altered the Na(+), K(+)-ATPase activity. In conclusion,
      the tellurium atom of PEBT is crucial for the catalytic oxidation of sulfhydryl
      groups from thiols of low molecular weight and from Na(+), K(+)-ATPase. 

PMID- 23955423
TI  - Blood manganese concentration is elevated in infants with iron deficiency.
AB  - The present study was done to determine whether blood Mn concentration is
      elevated in iron-deficient infants. Thirty-one infants with iron deficiency and
      thirty-six control subjects (6-24 months of age) were tested for blood Mn
      concentration, complete blood counts, serum ferritin, and serum iron/transferring
      iron-binding capacity (Fe/TIBC). All the 31 iron-deficient infants were treated
      with iron supplement; however, 19 of them underwent blood Mn checkup again in
      compliance with follow-up schedule when their ferritin levels returned to the
      normal range. Iron therapies were done for 1-6 months (mean, 2.8; standard
      deviation, 1.6) using ferric hydroxide-polymaltose complex (6 mg/kg Fe(3+)
      daily). Infants with iron deficiency had a higher mean blood Mn concentration
      than controls (2.550 vs. 1.499 MUg/dL, respectively). After iron therapy, the
      blood Mn levels of iron-deficient infants significantly decreased compared to
      their pre-therapy levels (2.045 vs. 2.971 MUg/dL, respectively), and their
      hemoglobin and ferritin levels significantly increased. After adjustment for
      covariates (e.g., age and breast-feeding), multiple linear regression models
      showed that increased blood Mn levels were significantly associated with low
      serum ferritin and hemoglobin levels, whereas with Fe/TIBC there was only a
      tendency. Our results indicate that iron deficiency increases blood Mn levels in
      infants, presumably by increasing Mn absorption.

PMID- 23955424
TI  - Markers for nutrition studies: review of criteria for the evaluation of markers.
AB  - INTRODUCTION: Markers are important tools to assess the nutrition status and
      effects of nutrition interventions. There is currently insufficient consensus in
      nutrition sciences on how to evaluate markers, despite the need for properly
      evaluating them. OBJECTIVES: To identify the criteria for the evaluation of
      markers related to nutrition, health and disease and to propose generic criteria
      for evaluation. METHOD: The report on "Evaluation of Biomarker and Surrogate
      Endpoints in Chronic Disease" from the Institute of Medicine was the starting
      point for the literature search. Additionally, specific search strategies were
      developed for Pubmed. RESULTS: In nutrition, no set of criteria or systematic
      approach to evaluate markers is currently available. There is a reliance on the
      medical area where statistical methods have been developed to quantify the
      evaluation of markers. Even here, a systematic approach is lacking-markers are
      still evaluated on a case-by-case basis. The review of publications from the
      literature search resulted in a database with definitions, criteria for validity
      and the rationale behind the criteria. It was recognized that, in nutrition, a
      number of methodological aspects differ from medical research. CONCLUSIONS: The
      following criteria were identified as essential elements in the evaluation of
      markers: (1) the marker has a causal biological link with the endpoint, (2) there
      is a significant association between marker and endpoint in the target
      population, (3) marker changes consistently with the endpoint, e.g., in response
      to an intervention, and (4) change in the marker explains a substantial
      proportion of the change in the endpoint in response to the intervention.

PMID- 23955425
TI  - Environmental Effectors on the Inactivation of Human Adenoviruses in Water.
AB  - Environmental factors are highly relevant to the global dissemination of viral
      pathogens. However, the specific contribution of major effectors such as
      temperature and sunlight on the inactivation of waterborne viruses is not well
      characterized. In this study, the effect of temperature (7, 20, and 37  degrees
      C), UVB and UVA radiation on viral inactivation was evaluated in phosphate
      buffered saline (PBS), mineral water, wastewater, 1,000-fold diluted wastewater
      and seawater. The stability of human adenoviruses infectivity, known as human
      pathogens and indicators of fecal contamination, was monitored during 24 h, both
      in the dark and exposed to UV radiation by immunofluorescence assays. In the
      dark, no Human adenovirus (HAdV) inactivation was observed in PBS and mineral
      water at any of the temperatures studied, whereas at 37  degrees C in reactors
      with higher microbial concentration (wastewater, diluted wastewater, and
      seawater), decays between 2.5 and 5 log were recorded. UVB radiation showed a
      dramatic effect on HAdV inactivation and 6-log were achieved in all reactors by
      the end of the experiments. The effect of UVA showed to be dependent on the water
      matrix analyzed. At 20  degrees C, HAdV showed a 2-log decay in all reactors
      radiation while at 37  degrees C, results in wastewater, diluted wastewater, and
      seawater reactors were equivalent to those observed in the dark. These results
      suggest UVB radiation as the major environmental factor challenging viral
      inactivation, followed by biotic activity indirectly associated to higher
      temperatures and finally, by UVA radiation.

PMID- 23955426
TI  - Social support and suicidal ideation in Japan: are home visits by commissioned
      welfare volunteers associated with a lower risk of suicidal ideation among
      elderly people in the community?
AB  - AIMS: Social support has consistently been reported to be effective in reducing
      suicidal ideation. This cross-sectional study was performed to determine whether
      home visits by commissioned welfare volunteers (i.e., organizations of community
      residents appointed by national or prefectural governments) are associated with a
      lower risk of suicidal ideation among the elderly. METHODS: In August 2010,
      questionnaires were sent to all residents aged >=65 years in three municipalities
      (n = 21,232) in Okayama prefecture, Japan, and 13,929 returned the questionnaire
      (response rate: 65.6%). We finally analyzed 11,218 subjects. Both home visits by
      commissioned welfare volunteers and suicidal ideation within the last 30 days
      were assessed in the questionnaire. Odds ratios (ORs) and 95% confidence
      intervals (CIs) for suicidal ideation were calculated adjusting for age, sex,
      educational attainment, and marital status. We then additionally adjusted for
      instrumental and emotional support, separately. RESULTS: The prevalence of
      suicidal ideation was 10.0% and higher in women than in men (11.4% vs. 8.0%).
      Home visits were significantly associated with a lower risk of suicidal ideation
      after adjusting for instrumental and emotional support, respectively (OR: 0.60,
      95% CI: 0.53-0.69; OR: 0.67, 95% CI: 0.59-0.78). In sex-stratified analysis, the
      association was clearer for women than for men: the corresponding ORs among women
      were 0.55 (95% CI: 0.46-0.65) and 0.61 (95% CI: 0.52-0.73), whereas they were
      0.71 (95% CI: 0.56-0.90) and 0.78 (95% CI: 0.61-0.99) among men. CONCLUSION: Our
      findings suggest that home visits by commissioned welfare volunteers are
      significantly associated with lower suicidal ideation among the elderly,
      particularly in women.

PMID- 23955427
TI  - Outcomes with FOLFIRINOX for borderline resectable and locally unresectable
      pancreatic cancer.
AB  - BACKGROUND: Trials examining FOLFIRINOX in metastatic pancreatic cancer
      demonstrate higher response rates compared to gemcitabine-based regimens. There
      is currently limited experience with neoadjuvant FOLFIRINOX in pancreatic cancer.
      METHODS: Retrospective review of outcomes of patients with borderline resectable
      or locally unresectable pancreatic cancer who were recommended to undergo
      neoadjuvant treatment with FOLFIRINOX. RESULTS: FOLFIRINOX was recommended for 25
      patients with pancreatic cancer, 13 (52%) unresectable and 12 (48%) borderline
      resectable. Four patients (16%) refused treatment or were lost to follow-up.
      Twenty-one patients (84%) were treated with a median of 4.7 cycles. Six patients
      (29%) required dose reductions secondary to toxicity. Two patients (9%) were
      unable to tolerate treatment and three patients (14%) had disease progression on
      treatment. Seven patients (33%) underwent surgical resection following treatment
      with FOLFIRINOX alone, 2 (10%) of which were initially unresectable. Two patients
      underwent resection following FOLFIRINOX + stereotactic body radiation therapy
      (SBRT). The R0 resection rate for patients treated with FOLFIRINOX +/- SBRT was
      33% (55% borderline resectable, 10% unresectable). A total of five patients (24%)
      demonstrated a significant pathologic response. CONCLUSIONS: FOLFIRINOX is a
      biologically active regimen in borderline resectable and locally unresectable
      pancreatic cancer with encouraging R0 resection and pathologic response rates.

PMID- 23955428
TI  - ArtR, a novel sRNA of Staphylococcus aureus, regulates alpha-toxin expression by
      targeting the 5' UTR of sarT mRNA.
AB  - Recent studies point to the importance of small-noncoding RNAs (sRNAs) in
      bacterial virulence control. In Staphylococcus aureus, functional dissections of
      sRNAs are limited to RNA III, SprD, RsaE, SprA1, and SSR42 only. Here, we report
      the identification and functional analyses of a novel sRNA, which we have
      designated ArtR. Our data show that the AgrA protein can bind to the artR
      promoter and repress artR transcription, suggesting that, after RNA III, ArtR is
      the second sRNA regulated by AgrA. Furthermore, ArtR is unique in S. aureus and
      involved in virulence regulation by activating alpha-toxin expression. ArtR
      promotes the degradation of sarT mRNA by RNase III and arrests the translation of
      SarT by direct binding to the 5' untranslated region of the sarT mRNA, suggesting
      that the activation of ArtR on the alpha-toxin expression was through SarT. This
      study reveals another kind of staphylococcal regulatory small RNA that plays a
      role in virulence control. It also indicates the diversity of small RNA-target
      mRNA interactions and how these multiple interactions can mediate virulence
      regulation in this pathogen. 

PMID- 23955430
TI  - Cold-shock RNA-binding protein CspR is also exposed to the surface of
      Enterococcus faecalis.
AB  - CspR has been characterized recently as a cold-shock RNA-binding protein in
      Enterococcus faecalis, a natural member of the gastro-intestinal tract capable of
      switching from a commensal relationship with the host to an important nosocomial
      pathogen. In addition to its involvement in the cold-shock response, CspR also
      plays a role in the long-term survival and virulence of E. faecalis. In the
      present study, we demonstrated that anti-CspR immune rabbit serum protected
      larvae of Galleria mellonella against a lethal challenge of the WT strain. These
      results suggested that CspR might have a surface location. This hypothesis was
      verified by Western blot that showed detection of CspR in the total as well as in
      the surface protein fraction. In addition, identification of surface polypeptides
      by proteolytic shaving of intact bacterial cells followed by liquid
      chromatography-MS-MS revealed that cold-shock proteins (EF1367, EF2939 and CspR)
      were present on the cell surface. Lastly, anti-CspR immune rabbit serum was used
      for immunolabelling and detected with colloidal gold-labelled goat anti-rabbit
      IgG in order to determine the immunolocalization of CspR on E. faecalis WT
      strain. Electron microscopy images confirmed that the cold-shock protein RNA
      binding protein CspR was present in both cytoplasmic and surface parts of the
      cell. These data strongly suggest that CspR, in addition to being located
      intracellularly, is also present in the extracellular protein fraction of the
      cells and has important functions in the infection process of Galleria larvae. 

PMID- 23955429
TI  - Development and characterization of a continuous macrophage cell line, LRTM,
      derived from thymus of Labeo rohita (Hamilton 1822).
AB  - A long-term thymic macrophage cell line from the thymus explants of Labeo rohita
      designated as LRTM (L. rohita thymic macrophages) was established, which has been
      maintained in culture for more than 1 yr. This cell line designated LRTM cells
      have been subcultured for 70 passages. The cells shape was initially long and
      elongated; with subsequent passages, the cells became short and epithelial like.
      The cells exhibited optimum growth in L-15 containing 10% fetal bovine serum and
      also in Dulbecco's modified Eagle's medium at 37 degrees C with 5% CO2 and showed
      85+-% viability after 12 mo storage in liquid nitrogen. In addition, cells showed
      nonspecific esterase and surface expression of Fc receptors for immunoglobulin G
      and classes I and II major histocompatibility complex antigens. These
      observations confirmed that this cell line had the morphologic and functional
      features as a macrophage. The cells exhibited phagocytic activity by engulfing
      yeast cells as well as fluorescent latex beads, which was demonstrated by
      scanning electron microscopy and Giemsa staining. The long-term cultured cells
      show rapid production of reactive oxygen and nitrogen intermediates following
      stimulation with lipopolysaccharides and phorbol miristate acetate (PMA). Mostly,
      all the cells were alpha napthyl esterase acetate positive. After stimulation
      with PMA and lipopolysaccharide, cultured fish macrophages produced reactive
      oxygen and nitrogen intermediates. The karyotype analysis showed that these cells
      have a tetraploid karyotype with 100 chromosomes in each cell, indicating that
      they are normal L. rohita cells. Amplification, sequencing, and alignment of
      fragments of two mitochondrial genes 12S rRNA from rohu confirmed that the cell
      line originated from L. rohita. This cell line should be useful for studying the
      role of thymic macrophages in differentiation and maturation of thymocytes and
      can be source of macrophage-specific enzymes and cytokines. The macrophage cell
      line will be invaluable in studies of pathogen/macrophage interactions, the
      mechanisms of macrophage antimicrobial effector functions and the contribution of
      macrophages to the specific immune responses of teleosts. 

PMID- 23955432
TI  - Modeling of constrained articular cartilage growth in an intact knee with focal
      knee resurfacing metal implant.
AB  - The purpose of the present study was to develop a model to simulate the articular
      cartilage growth in an intact knee model with a metal implant replacing a
      degenerated portion of the femoral cartilage. The human knee joint was
      approximated with a simplified axisymmetric shape of the femoral condyle along
      with the cartilage, meniscus and bones. Two individually growing constituents
      (proteoglycans and collagen) bound to solid matrix were considered in the solid
      phase of the cartilage. The cartilage behavior was modeled with a nonlinear
      biphasic porohyperelastic material model, and meniscus with a transversely
      isotropic linear biphasic poroelastic material model. Two criteria (permeation
      and shear), both driven by mechanical loading, were considered to trigger the
      growth in the solid constituents. Mechanical loading with sixty heavy cycles was
      considered to represent daily walking activity. The growth algorithm was
      implemented for 90 days after implantation. The results from simulations show
      that both cartilage layers were more stimulated near the implant which lead to
      more growth of the cartilage near the defect. The method developed in the present
      work could be a powerful technique if more accurate material data and growth laws
      were available. 

PMID- 23955433
TI  - Controlling the orientation of spin-correlated radical pairs by covalent linkage
      to nanoporous anodic aluminum oxide membranes.
AB  - Ordered multi-spin assemblies are required for developing solid-state molecule
      based spintronics. A linear donor-chromophore-acceptor (D-C-A) molecule was
      covalently attached inside the 150 nm diam. nanopores of an anodic aluminum oxide
      (AAO) membrane. Photoexcitation of D-C-A in a 343 mT magnetic field results in
      sub-nanosecond, two-step electron transfer to yield the spin-correlated radical
      ion pair (SCRP) (1)(D(+)-C-A(-)), which then undergoes radical pair intersystem
      crossing (RP-ISC) to yield (3)(D(+)-C-A(-)). RP-ISC results in S-T0 mixing to
      selectively populate the coherent superposition states |S'> and |T'>. Microwave
      induced transitions between these states and the unpopulated |T(+1)> and |T(-1)>
      states result in spin-polarized time-resolved EPR (TREPR) spectra. The dependence
      of the electron spin polarization (ESP) phase of the TREPR spectra on the
      orientation of the AAO membrane pores relative to the externally applied magnetic
      field is used to determine the overall orientation of the SCRPs within the pores
      at room temperature.

PMID- 23955431
TI  - Randomized, placebo-controlled trial to assess the safety and immunogenicity of
      an adenovirus type 35-based circumsporozoite malaria vaccine in healthy adults.
AB  - Malaria results in over 650,000 deaths each year; thus, there is an urgent need
      for an effective vaccine. Pre-clinical studies and recently reported human trials
      suggest that pre-erythrocytic stage vaccines can provide protection against
      infection. A Phase 1, randomized, placebo-controlled, dose-escalation study was
      conducted with a vaccine composed of a replication-deficient adenovirus-35
      backbone with P. falciparum circumsporozoite (CS) surface antigen (Ad35.CS.01).
      Healthy adult subjects received three doses of 10 (8), 10 (9), 10 (10), or 10
      (11) vp/mL Ad35.CS.01 vaccine or saline placebo intramuscularly at 0, 1, and 6-mo
      intervals. Adverse events were assessed and anti-CS antibody responses were
      determined by ELISA. Seventy-two individuals were enrolled, with age, gender, and
      ethnicity similar across each study arm. While the vaccine was generally well
      tolerated, adverse events were more frequent in the highest dose groups (10 (10)
      and 10 (11) vp/mL). More robust humoral responses were also noted at the highest
      doses, with 73% developing a positive ELISA response after the three dose series
      of 10 (11) vp/mL. The Ad35.CS.01 vaccine was most immunogenic at the highest
      dosages (10 (10) and 10 (11) vp/mL). Reactogenicity findings were more common
      after the 10 (11) vp/mL dose, although most were mild or moderate in nature and
      resolved without therapy.

PMID- 23955434
TI  - The performance analysis of a real-time integrated INS/GPS vehicle navigation
      system with abnormal GPS measurement elimination.
AB  - The integration of an Inertial Navigation System (INS) and the Global Positioning
      System (GPS) is common in mobile mapping and navigation applications to
      seamlessly determine the position, velocity, and orientation of the mobile
      platform. In most INS/GPS integrated architectures, the GPS is considered to be
      an accurate reference with which to correct for the systematic errors of the
      inertial sensors, which are composed of biases, scale factors and drift. However,
      the GPS receiver may produce abnormal pseudo-range errors mainly caused by
      ionospheric delay, tropospheric delay and the multipath effect. These errors
      degrade the overall position accuracy of an integrated system that uses
      conventional INS/GPS integration strategies such as loosely coupled (LC) and
      tightly coupled (TC) schemes. Conventional tightly coupled INS/GPS integration
      schemes apply the Klobuchar model and the Hopfield model to reduce pseudo-range
      delays caused by ionospheric delay and tropospheric delay, respectively, but do
      not address the multipath problem. However, the multipath effect (from reflected
      GPS signals) affects the position error far more significantly in a consumer
      grade GPS receiver than in an expensive, geodetic-grade GPS receiver. To avoid
      this problem, a new integrated INS/GPS architecture is proposed. The proposed
      method is described and applied in a real-time integrated system with two
      integration strategies, namely, loosely coupled and tightly coupled schemes,
      respectively. To verify the effectiveness of the proposed method, field tests
      with various scenarios are conducted and the results are compared with a reliable
      reference system. 

PMID- 23955435
TI  - ESB-based Sensor Web integration for the prediction of electric power supply
      system vulnerability.
AB  - Electric power supply companies increasingly rely on enterprise IT systems to
      provide them with a comprehensive view of the state of the distribution network.
      Within a utility-wide network, enterprise IT systems collect data from various
      metering devices. Such data can be effectively used for the prediction of power
      supply network vulnerability. The purpose of this paper is to present the
      Enterprise Service Bus (ESB)-based Sensor Web integration solution that we have
      developed with the purpose of enabling prediction of power supply network
      vulnerability, in terms of a prediction of defect probability for a particular
      network element. We will give an example of its usage and demonstrate our
      vulnerability prediction model on data collected from two different power supply
      companies. The proposed solution is an extension of the GinisSense Sensor Web
      based architecture for collecting, processing, analyzing, decision making and
      alerting based on the data received from heterogeneous data sources. In this
      case, GinisSense has been upgraded to be capable of operating in an ESB
      environment and combine Sensor Web and GIS technologies to enable prediction of
      electric power supply system vulnerability. Aside from electrical values, the
      proposed solution gathers ambient values from additional sensors installed in the
      existing power supply network infrastructure. GinisSense aggregates gathered data
      according to an adapted Omnibus data fusion model and applies decision-making
      logic on the aggregated data. Detected vulnerabilities are visualized to end
      users through means of a specialized Web GIS application. 

PMID- 23955436
TI  - Integration of metal oxide nanowires in flexible gas sensing devices.
AB  - Metal oxide nanowires are very promising active materials for different
      applications, especially in the field of gas sensors. Advances in fabrication
      technologies now allow the preparation of nanowires on flexible substrates,
      expanding the potential market of the resulting sensors. The critical steps for
      the large-scale preparation of reliable sensing devices are the elimination of
      high temperatures processes and the stretchability of the entire final device,
      including the active material. Direct growth on flexible substrates and post
      growth procedures have been successfully used for the preparation of gas sensors.
      The paper will summarize the procedures used for the preparation of flexible and
      wearable gas sensors prototypes with an overlook of the challenges and the future
      perspectives concerning this field. 

PMID- 23955437
TI  - Advanced glycation end products delay corneal epithelial wound healing through
      reactive oxygen species generation.
AB  - Delayed healing of corneal epithelial wounds is a serious complication in
      diabetes. Advanced glycation end products (AGEs) are intimately associated with
      the diabetic complications and are deleterious to the wound healing process.
      However, the effect of AGEs on corneal epithelial wound healing has not yet been
      evaluated. In the present study, we investigated the effect of AGE-modified
      bovine serum albumin (BSA) on corneal epithelial wound healing and its underlying
      mechanisms. Our data showed that AGE-BSA significantly increased the generation
      of intracellular ROS in telomerase-immortalized human corneal epithelial cells.
      However, the generation of intracellular ROS was completely inhibited by
      antioxidant N-acetylcysteine (NAC), anti-receptor of AGEs (RAGE) antibodies, or
      the inhibitor of NADPH oxidase. Moreover, AGE-BSA increased NADPH oxidase
      activity and protein expression of NADPH oxidase subunits, p22phox and Nox4, but
      anti-RAGE antibodies eliminated these effects. Furthermore, prevention of
      intracellular ROS generation using NAC or anti-RAGE antibodies rescued AGE-BSA
      delayed epithelial wound healing in porcine corneal organ culture. In conclusion,
      our results demonstrated that AGE-BSA impaired corneal epithelial wound healing
      ex vivo. AGE-BSA increased intracellular ROS generation through NADPH oxidase
      activation, which accounted for the delayed corneal epithelial wound healing.
      These results may provide better insights for understanding the mechanism of
      delayed healing of corneal epithelial wounds in diabetes.

PMID- 23955439
TI  - Understanding safety climate in small automobile collision repair shops.
AB  - BACKGROUND: In the United States, approximately 236,000 people work in 37,600
      auto collision-repair businesses. Workers in the collision-repair industry may be
      exposed to a wide range of physical and chemical hazards. METHODS: This
      manuscript examines the relationship of safety climate as reported by collision
      repair shop workers and owners to: (1) an independent business safety assessment,
      and (2) employee self-reported work practices. The study was conducted in the
      Twin Cities metropolitan area. RESULTS: A total of 199 workers from 49 collision
      shops completed a survey of self-reported work practices and safety climate.
      Surveys were completed by an owner or manager in all but three shops. In general,
      self-reported work practices were poor. Workers' scores on safety climate were
      uniformly lower than those of owners. For workers, there was no correlation
      between how well the business scored on an independent audit of business safety
      practices and the safety climate measures they reported. For owners, however,
      there was a positive correlation between safety climate scores and the business
      safety assessment. For workers, safety rules and procedures were associated with
      improved work practices for those engaged in both painting-related and body
      technician-related activities. CONCLUSIONS: The enforcement of safety rules and
      procedures emerged as a strong factor positively affecting self-reported work
      practices. These findings identify a simple, cost effective path to reducing
      hazards in small workplaces.

PMID- 23955438
TI  - Nogo/RTN4 isoforms and RTN3 expression protect SH-SY5Y cells against multiple
      death insults.
AB  - Among the members of the reticulon (RTN) family, Nogo-A/RTN4A, a prominent myelin
      associated neurite growth inhibitory protein, and RTN3 are highly expressed in
      neurons. However, neuronal cell-autonomous functions of Nogo-A, as well as other
      members of the RTN family, are unclear. We show here that SH-SY5Y neuroblastoma
      cells stably over-expressing either two of the three major isoforms of Nogo/RTN4
      (Nogo-A and Nogo-B) or a major isoform of RTN3 were protected against cell death
      induced by a battery of apoptosis-inducing agents (including serum deprivation,
      staurosporine, etoposide, and H2O2) compared to vector-transfected control cells.
      Nogo-A, -B, and RTN3 are particularly effective in terms of protection against
      H2O2-induced increase in intracellular reactive oxygen species levels and ensuing
      apoptotic and autophagic cell death. Expression of these RTNs upregulated basal
      levels of Bax, activated Bax, and activated caspase 3, but did not exhibit an
      enhanced ER stress response. The protective effect of RTNs is also not dependent
      on classical survival-promoting signaling pathways such as Akt and Erk kinase
      pathways. Neuron-enriched Nogo-A/Rtn4A and RTN3 may, therefore, exert a
      protective effect on neuronal cells against death stimuli, and elevation of their
      levels during injury may have a cell-autonomous survival-promoting function. 

PMID- 23955440
TI  - An object-based image analysis approach for aquaculture ponds precise mapping and
      monitoring: a case study of Tam Giang-Cau Hai Lagoon, Vietnam.
AB  - Monitoring and mapping shrimp farms, including their impact on land cover and
      land use, is critical to the sustainable management and planning of coastal
      zones. In this work, a methodology was proposed to set up a cost-effective and
      reproducible procedure that made use of satellite remote sensing, object-based
      classification approach, and open-source software for mapping aquaculture areas
      with high planimetric and thematic accuracy between 2005 and 2008. The analysis
      focused on two characteristic areas of interest of the Tam Giang-Cau Hai Lagoon
      (in central Vietnam), which have similar farming systems to other coastal
      aquaculture worldwide: the first was primarily characterised by locally referred
      "low tide" shrimp ponds, which are partially submerged areas; the second by
      earthed shrimp ponds, locally referred to as "high tide" ponds, which are non
      submerged areas on the lagoon coast. The approach was based on the region-growing
      segmentation of high- and very high-resolution panchromatic images, SPOT5 and
      Worldview-1, and the unsupervised clustering classifier ISOSEG embedded on SPRING
      non-commercial software. The results, the accuracy of which was tested with a
      field-based aquaculture inventory, showed that in favourable situations (high
      tide shrimp ponds), the classification results provided high rates of accuracy
      (>95 %) through a fully automatic object-based classification. In unfavourable
      situations (low tide shrimp ponds), the performance degraded due to the low
      contrast between the water and the pond embankments. In these situations, the
      automatic results were improved by manual delineation of the embankments.
      Worldview-1 necessarily showed better thematic accuracy, and precise maps have
      been realised at a scale of up to 1:2,000. However, SPOT5 provided comparable
      results in terms of number of correctly classified ponds, but less accurate
      results in terms of the precision of mapped features. The procedure also
      demonstrated high degrees of reproducibility because it was applied to images
      with different spatial resolutions in an area that, during the investigated
      period, did not experience significant land cover changes. 

PMID- 23955441
TI  - Avanafil: a review of its use in patients with erectile dysfunction.
AB  - Avanafil (STENDRATM, SPEDRATM, ZepeeedTM) is an oral phosphodiesterase type 5
      inhibitor indicated for the treatment of erectile dysfunction. Avanafil is
      rapidly absorbed after oral administration, with a median time to maximum plasma
      concentration of 30 to 45 min. In a 12-week, randomized, double-blind, placebo
      controlled, multicentre trial in patients with erectile dysfunction, avanafil 50,
      100 and 200 mg recipients had significantly greater improvements from baseline
      than placebo recipients in mean international index of erectile dysfunction
      erectile function domain scores and in successful vaginal penetration and sexual
      intercourse attempts (coprimary endpoints). Treatment effects were significantly
      larger in avanafil 100 and 200 mg recipients than 50 mg recipients. For avanafil
      recipients, approximately two-thirds of attempts at sexual intercourse that were
      made prior to 15 min, or more than 6 h, after drug administration were
      successful, compared with approximately one-quarter of attempts made during these
      time periods by placebo recipients. In trials in patients with erectile
      dysfunction in association with diabetes mellitus, and after nerve-sparing
      radical prostatectomy, avanafil 100 or 200 mg was significantly more efficacious
      than placebo for primary and most secondary endpoints. Avanafil was generally
      well tolerated in the above-mentioned studies. In a pooled analysis of three
      clinical trials, <=2 % of avanafil and placebo recipients discontinued treatment
      because of adverse events. During extended treatment with avanafil for >52 weeks,
      2.8 % of patients discontinued treatment because of adverse reactions and there
      were no drug-related serious adverse events.

PMID- 23955442
TI  - Differential utilization of TATA box-binding protein (TBP) and TBP-related factor
      1 (TRF1) at different classes of RNA polymerase III promoters.
AB  - In the fruit fly Drosophila melanogaster, RNA polymerase III transcription was
      found to be dependent not upon the canonical TATA box-binding protein (TBP) but
      instead upon the TBP-related factor 1 (TRF1) (Takada, S., Lis, J. T., Zhou, S.,
      and Tjian, R. (2000) Cell 101, 459-469). Here we confirm that transcription of
      fly tRNA genes requires TRF1. However, we unexpectedly find that U6 snRNA gene
      promoters are occupied primarily by TBP in cells and that knockdown of TBP, but
      not TRF1, inhibits U6 transcription in cells. Moreover, U6 transcription in vitro
      effectively utilizes TBP, whereas TBP cannot substitute for TRF1 to promote tRNA
      transcription in vitro. Thus, in fruit flies, different classes of RNA polymerase
      III promoters differentially utilize TBP and TRF1 for the initiation of
      transcription. 

PMID- 23955443
TI  - DNA damage processing by human 8-oxoguanine-DNA glycosylase mutants with the
      occluded active site.
AB  - 8-Oxoguanine-DNA glycosylase (OGG1) removes premutagenic lesion 8-oxoguanine (8
      oxo-G) from DNA and then nicks the nascent abasic (apurinic/apyrimidinic) site by
      beta-elimination. Although the structure of OGG1 bound to damaged DNA is known,
      the dynamic aspects of 8-oxo-G recognition are not well understood. To comprehend
      the mechanisms of substrate recognition and processing, we have constructed OGG1
      mutants with the active site occluded by replacement of Cys-253, which forms a
      wall of the base-binding pocket, with bulky leucine or isoleucine. The
      conformational dynamics of OGG1 mutants were characterized by single-turnover
      kinetics and stopped-flow kinetics with fluorescent detection. Additionally, the
      conformational mobility of wild type and the mutant OGG1 substrate complex was
      assessed using molecular dynamics simulations. Although pocket occlusion
      distorted the active site and greatly decreased the catalytic activity of OGG1,
      it did not fully prevent processing of 8-oxo-G and apurinic/apyrimidinic sites.
      Both mutants were notably stimulated in the presence of free 8-bromoguanine,
      indicating that this base can bind to the distorted OGG1 and facilitate beta
      elimination. The results agree with the concept of enzyme plasticity, suggesting
      that the active site of OGG1 is flexible enough to compensate partially for
      distortions caused by mutation. 

PMID- 23955444
TI  - Are samples in your freezer still good for biomarker discovery?

PMID- 23955445
TI  - Ex Africa semper aliquid novi.

PMID- 23955447
TI  - Identification of one or two alpha-globin gene deletions by isoelectric focusing
      electrophoresis.
AB  - OBJECTIVES: To investigate the utility of isoelectric focusing electrophoresis
      (IEF) for identifying patients with alpha-thalassemia, which results from the
      deletion of 1 or more of the alpha-globin genes. METHODS: Samples were selected
      based on their hemoglobin H (HbH) concentration observed using IEF. The samples
      were analyzed for the most common alpha-globin gene deletions using molecular
      analysis. RESULTS: alpha-Globin gene deletions corresponding to alpha-thalassemia
      trait or silent carrier were observed in all samples with the HbH less than 2%
      phenotype. The genotypes of the specimens with HbH greater than 5% were
      consistent with HbH disease, while the wild-type phenotype control samples showed
      a wild-type genotype. CONCLUSIONS: Low concentrations of HbH can be detected in a
      patient with 1 or 2 alpha-gene deletions using IEF.

PMID- 23955446
TI  - Evaluation of CCR3 as a basophil activation marker.
AB  - OBJECTIVES: Recent reports have provided conflicting evidence on the stability of
      CCR3 expression on the surface of basophils. Hence we wanted to independently
      evaluate the diagnostic usefulness of CCR3 as a surrogate marker of basophil
      activation and function. METHODS: We examined the correlative relationship
      between CCR3 expression on the surface of donor basophils and histamine release
      after donor basophils were treated with agonistic antibodies directed against the
      high-affinity IgE-Fc receptor and serum samples from 80 individuals displaying
      symptoms of chronic urticaria (CU). RESULTS: We observed that CCR3 was
      significantly downregulated on donor basophils treated with the agonistic
      antibody and CU-patient serum that demonstrated positive "histamine-releasing
      activity" (HRA scores >10). However, CCR3 downregulation was also observed on
      donor basophils incubated with more than 40% of CU-patient serum samples with HRA
      scores less than or equal to 10. CONCLUSIONS: Overall our data show that CCR3
      demonstrates adequate sensitivity (83%) but weak specificity (59%) in its ability
      to reliably identify histamine-releasing activated basophils.

PMID- 23955448
TI  - Evaluation of the BD Vacutainer Plus Urine C&S Preservative Tubes compared with
      nonpreservative urine samples stored at 4 degrees C and room temperature.
AB  - OBJECTIVES: The stability of urine specimens submitted for culture remains a
      challenge for many laboratories because of delays in specimen transport. We
      evaluated the usefulness of BD Vacutainer Plus Urine C&S Preservative Tube in
      ensuring specimen stability. METHODS: Clinical urine specimens collected in
      sterile collection cups (n = 110) were plated onto sheep blood and MacConkey agar
      following standard laboratory procedures guidelines. Thereafter, specimens were
      divided into 3 storage conditions: nonpreservative, refrigerated;
      nonpreservative, room temperature (RT); BD Vacutainer Plus Urine C&S Preservative
      Tube, RT. For each sample type, additional cultures were set up at 2, 4, 24, and
      48 hours. RESULTS: Initially, 18 specimens had no growth, 32 showed mixed skin
      flora, and 60 yielded at least 1 uropathogen. Increased colony counts of
      uropathogens were observed for nonpreserved urine samples stored at RT; these
      changes were statistically significant. Minor differences between refrigerated
      urine samples and BD Vacutainer Plus Urine C&S Preservative Tube samples were
      seen but were not statistically significant. CONCLUSIONS: The use of preservative
      containing collection tubes is desirable to ensure specimen stability when prompt
      processing or refrigeration is not feasible.

PMID- 23955449
TI  - MS-based monitoring of proteolytic decay of synthetic reporter peptides for
      quality control of plasma and serum specimens.
AB  - OBJECTIVES: To determine the preanalytical quality of serum and plasma by
      monitoring the time-dependent ex vivo decay of a synthetic reporter peptide (RP)
      with liquid chromatography/mass spectrometry (LC/MS). METHODS: Serum and plasma
      specimens were spiked with the RP and proteolytic fragments were monitored with
      LC/MS at different preanalytical time points ranging from 2 to 24 hours after
      blood withdrawal. RESULTS: The concentration of fragments changed in a time
      dependent manner, and respective peptide profiles were used to classify specimens
      according to their preanalytical time span. Classification accuracy was high,
      with values always above 0.89 for areas under receiver operating characteristic
      curves. CONCLUSIONS: This "proteomics degradation clock" can be used to estimate
      the preanalytical quality of serum and plasma and might have impact on quality
      control procedures of biobanking repositories.

PMID- 23955450
TI  - Physicians' and nurses' satisfaction with the clinical laboratory service of
      Gondar University Hospital, northwest Ethiopia.
AB  - OBJECTIVES: To assess physicians' and nurses' satisfaction with the service
      provided by the laboratory at Gondar University Hospital. METHODS: We conducted a
      cross-sectional study involving 196 nurses and physicians. RESULTS: Overall level
      of satisfaction was 51.1% for nurses and 51.5% for physicians. Lack of
      consistency in the quality of laboratory work, absence of a timely report of
      critical values, test turnaround time, acceptability of results released, and
      reporting of reference ranges with test results were areas mentioned as sources
      of dissatisfaction. CONCLUSIONS: The study showed wide room for improvement. In
      addition to taking intervention, root causes of dissatisfaction need to be
      investigated and means of improving the satisfaction level should be designed and
      implemented.

PMID- 23955451
TI  - Clinicopathologic significance of combined hepatocellular-cholangiocarcinoma with
      stem cell subtype components with reference to the expression of putative stem
      cell markers.
AB  - OBJECTIVES: To examine the clinicopathologic features of combined hepatocellular
      cholangiocarcinoma (HC-CC), which the World Health Organization (WHO) proposed
      classifying into 2 types, and the expression of delta-like 1 homolog (DLK1), as
      well as putative stem cell markers, such as NCAM/CD56 and CD133. METHODS: In this
      study we examined the expression of stem cell markers using immunohistochemistry.
      RESULTS: Thirty-six cases of combined HC-CC were subclassified into 24 cases,
      with more than 5% stem cell features (group B) and 12 cases with less than 5%
      stem cell areas (group A). The postoperative overall survival rate was worse for
      group B than for group A. DLK1 was frequently expressed in group B cases compared
      with group A, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma
      cases. CONCLUSIONS: The 2010 WHO classification seems important for elucidating
      the pathogenesis of stem cell-related liver cancers.

PMID- 23955452
TI  - Poorly differentiated colorectal cancers: correlation of microsatellite
      instability with clinicopathologic features and survival.
AB  - OBJECTIVES: To evaluate the association of microsatellite instability (MSI) with
      clinicopathologic features and oncologic outcomes in patients with poorly
      differentiated colorectal cancer (PD). METHODS: Study patients were divided into
      well-differentiated colorectal cancer (WD) and PD, which were compared according
      to histologic differentiation and MSI status. RESULTS: Among 1,941 patients, PD
      was more frequent among microsatellite-unstable tumors (23.6%) than among
      microsatellite-stable (MSS) tumors (4.2%, P < .001). Patients with PD had worse 4
      year overall survival rates than patients with WD (78.6% vs 88.2%, P = 0.010).
      Compared with MSS-PD tumors, MSI-PD tumors were characterized by right-colon
      predilection, larger size, and infrequent lymph node metastasis (P < .001 to P =
      .007). CONCLUSIONS: The clinicopathologic characteristics of PD were closely
      associated with those of MSI. The outcomes of MSI-PD tumors were better than
      those of MSS-PD tumors, but this finding did not reach statistical significance.

PMID- 23955453
TI  - Analysis of cutaneous lymphomas in a medical center in Bahia, Brazil.
AB  - OBJECTIVES: To evaluate the frequency of the different types of cutaneous
      lymphoma (CL) in 1 university hospital in Brazil and compare this frequency with
      those observed in other countries. METHODS: After review, 72 (84.7%) cases of
      primary cutaneous T-cell lymphoma (CTCL) and 13 (15.3%) cases of primary
      cutaneous B-cell lymphoma (CBCL) were included. RESULTS: Of the CTCLs, 40.3% were
      mycosis fungoides (MF); 26.4% were adult T-cell leukemias/lymphomas (ATLs); 23.6%
      were peripheral T-cell lymphomas, unspecified; and 8.3% were anaplastic large
      cell lymphomas. Of the MF cases, 17.2% progressed to transformed MF. Five-year
      survival for primary human T-cell lymphotropic virus type 1-negative CTCL, ATL,
      and CBCL was 64.0%, 42.1%, and 62.5%, respectively. MF and ATL were the most
      frequent primary CTCLs. CONCLUSIONS: The frequencies observed here are close to
      those observed in Peru but different from those of European countries.
      Unfortunately, the World Health Organization/European Organization of Research
      and Treatment of Cancer classification does not include primary cutaneous ATL.

PMID- 23955454
TI  - B-cell transcription factor expression and immunoglobulin gene rearrangement
      frequency in acute myeloid leukemia with t(8;21)(q22;q22).
AB  - OBJECTIVES: To assess a large series of patients with acute myeloid leukemia
      (AML) with t(8;21) for both IGH@ and IGK@ B-cell gene rearrangements and for
      expression of PAX5, OCT2, and Bob.1 by immunohistochemistry and expression of
      CD19, CD79a, CD20, and CD22 by flow cytometry immunophenotyping. METHODS: A total
      of 48 cases of AML with t(8;21)(q22;q22) were evaluated by immunohistochemistry
      and/or heavy chain and light chain immunoglobulin rearrangement studies where
      paraffin-embedded and/or fresh frozen material was available for study;
      previously performed flow cytometry studies were also reviewed in available
      cases. RESULTS: Our study yielded 1 of 19 cases of AML with t(8;21) with an IGH@
      gene rearrangement; blasts were associated with weak PAX5 expression. In
      addition, expression of antigens CD79a by flow cytometry and OCT2 by
      immunohistochemistry were highly associated with PAX5 expression, and CD19 was
      expressed in most cases assessed. CONCLUSIONS: Although B-cell antigen and B-cell
      transcription factor expression is seen in the majority of AMLs with
      t(8;21)(q22;q22) and correlates with PAX5 expression, immunoglobulin gene
      rearrangements are an uncommon event in this group of leukemias.

PMID- 23955455
TI  - Frozen section diagnosis: is there discordance between what pathologists say and
      what surgeons hear?
AB  - OBJECTIVES: Communication in various medical settings is subject to
      misinterpretation. The frozen section (FS) diagnosis in patient care is dependent
      on successful communication between pathologists and surgeons. However, very few
      studies looking at FS errors analyzed postanalytic communication issues. METHODS:
      A total of 300 consecutive cases, in which an FS was performed and corresponding
      surgical note was available, were studied. The FS diagnosis and surgeon's
      interpretation were recorded for all cases. Discrepancies were classified as
      major (clinical impact) or minor (no clinical impact). RESULTS: We found 8 (2.7%)
      miscommunications, all with only minor clinical impact. These were attributed
      mainly to the surgeon's misinterpretation of a deferred diagnosis. Also
      contributing to miscommunication was the pathologist's use of nonspecific
      terminology such as "favor" or "scattered." CONCLUSIONS: We found that the rate
      of miscommunicated FS diagnoses was low at our institution during the period of
      our study. However, the rate of miscommunication was similar to the much more
      widely recognized problem of sampling error.

PMID- 23955456
TI  - CD105 (endoglin) is highly overexpressed in a subset of cases of acute myeloid
      leukemias.
AB  - OBJECTIVES: To assess CD105 (endoglin) expression in 119 acute myeloid leukemia
      (AML) and 13 control cases using immunohistochemistry. METHODS: CD105 expression
      was assessed retrospectively by using immunohistochemistry in bone marrow
      specimens. RESULTS: CD105 was strongly and diffusely positive in all 9 (100%)
      AMLs with t(15;17)(q24.1;q21.2), 2 (100%) AMLs with t(8;21)(q22;q22), 1 (100%)
      AML with t(6;9)(p23;q34), 7 (28%) of 25 AMLs with myelodysplasia-related changes,
      1 (33%) of 3 therapy-related AMLs, 3 (16%) of 19 AMLs unclassifiable, 1 (14%) of
      7 AMLs with inv(16)(p13.1q22), and 5 (11%) of 45 AMLs not otherwise specified.
      Uninvolved bone marrow in these cases showed no CD105 expression by erythroid
      precursors, megakaryocytes, or endothelial or stromal cells. Two of 13 control
      bone marrow specimens showed partial CD105 positivity in myeloid cells. In 21
      strongly CD105+ AML cases tested for the IDH2 mutation, 9 (42%) were mutated (P =
      .004). CONCLUSIONS: These data suggest that CD105 could be a therapeutic target
      in a subset of patients with AML.

PMID- 23955457
TI  - An improved algorithm for activated protein C resistance and factor V Leiden
      screening.
AB  - OBJECTIVES: To evaluate the performance of a Russell viper venom-based activated
      protein C resistance (APCR) screening test relative to DNA analysis for the
      factor V Leiden mutation. METHODS: We evaluated the concordance between Pefakit
      APCR screening results and DNA analysis for 435 patients homozygous (n = 11),
      heterozygous (n = 310), or wild-type (n =114) for the G1691A allele. RESULTS:
      Using receiver operating characteristic analysis, we found that a cutoff of 1.89
      for the APCR ratio yields a sensitivity and specificity of 99.1%. In patients
      with discrepant genotype-phenotype correlation, their APCR may provide a more
      clinically relevant result. CONCLUSIONS: We compared several strategies for
      employing reflex testing and found that performing initial APCR screening
      followed by confirmatory molecular analysis on a subset of cases in the
      borderline regions between the diagnostic groups can reduce unnecessary testing
      by approximately 80% without compromising diagnostic accuracy.

PMID- 23955458
TI  - MYD88 L265P somatic mutation: its usefulness in the differential diagnosis of
      bone marrow involvement by B-cell lymphoproliferative disorders.
AB  - OBJECTIVES: To examine the usefulness of the MYD88 L265P somatic mutation in
      identifying cases of lymphoplasmacytic lymphoma (LPL) from other
      lymphoplasmacytic neoplasms in bone marrow biopsy specimens. METHODS: We studied
      64 bone marrow biopsy specimens with involvement by various small B-cell
      lymphomas or plasma cell myeloma. RESULTS: The MYD88 L265P somatic mutation was
      present in 13/13 cases of LPL, 1/13 cases of hairy cell leukemia, and absent in
      the other mature B-cell neoplasms tested. A test set of diagnostically
      challenging bone marrow cases with lymphoplasmacytoid morphology (B-cell
      lymphoma, not otherwise specified) was selected for additional review and
      reclassified, without knowledge of the MYD88 L265P status. Of those 16 cases, 7
      were positive for MYD88, including 4/4 cases that were reclassified as LPL during
      the review. CONCLUSIONS: Although not entirely specific, MYD88 L265P is a useful
      adjunct for bone marrow diagnosis in separating LPL from other small B-cell
      lymphomas and plasma cell myeloma.

PMID- 23955459
TI  - Relationship between Rosai-Dorfman disease and IgG4-related disease: study of 32
      cases.
AB  - OBJECTIVES: To assess the association between Rosai-Dorfman disease (RDD) and
      IgG4-related disease (IgG4-RD). METHODS: We studied the number of IgG4-positive
      plasma cells and the IgG4/IgG ratio in 32 biopsy specimens (13 nodal, 19
      extranodal) from 29 patients with RDD and compared the findings with those in
      IgG4-RD of the pancreas and reactive lymph nodes. We also assessed the number of
      FOXP3-positive regulatory T cells (Tregs) since they were reported to be
      increased in IgG4-RD. RESULTS: We found that RDD cases had much lower numbers of
      IgG4-positive plasma cells and lower IgG4/IgG ratios compared with IgG4-RD but
      were similar to reactive lymph nodes. Furthermore, RDD had lower numbers of FOXP3
      positive Tregs than did IgG4-RD. There were no significant differences in the
      number of IgG4-positive plasma cells and the IgG4/IgG ratio between the nodal and
      extranodal RDD cases. CONCLUSIONS: Our study suggests that RDD does not belong in
      the spectrum of IgG4-RD.

PMID- 23955460
TI  - Acute hepatitis with periportal confluent necrosis associated with human
      herpesvirus 6 infection in liver transplant patients.
AB  - OBJECTIVES: To correlate human herpesvirus 6 (HHV-6) viral load with pathologic
      features in graft acute hepatitis of unknown origin. METHODS: Liver frozen
      samples from 26 patients with graft hepatitis of unknown origin were available
      for HHV-6 DNA quantification. RESULTS: In 10 (38.5%) of 26 liver samples, HHV-6
      DNA was detectable, with a median viral load of 3.84 log10 copies/106 cells.
      Confluent periportal necrosis was observed in 4 of 10 patients and associated
      with high viral load. These 4 patients responded to antiviral therapy. Mild
      unspecific hepatitis was observed in 4 patients with low intragraft viral load
      and in 2 patients with high viral load in a context of deep immunosuppression.
      Patients with HHV-6-negative graft hepatitis disclosed lobular necrotico
      inflammatory activity without periportal necrosis. CONCLUSIONS: Our study
      provides data supporting the pathogenic role of HHV-6 for liver allografts. The
      presence of confluent periportal necrosis could be a clue for prompt diagnosis of
      HHV-6-induced graft hepatitis.

PMID- 23955461
TI  - Significant variation of immunohistochemical marker expression in paired primary
      and metastatic clear cell renal cell carcinomas.
AB  - OBJECTIVES: To compare the immunohistochemical expression of diagnostic markers
      in primary clear cell renal cell carcinomas (RCCs) and their matched metastases.
      METHODS: Tissue microarrays were constructed from 15 pairs of primary and
      metastatic clear cell RCCs and then evaluated for the immunohistochemical
      expression of renal cell carcinoma antigen (RCCA), kidney-specific cadherin,
      carbonic anhydrase IX (CAIX), and paired box genes 2 (PAX2) and 8 (PAX8).
      RESULTS: There was significantly higher overall marker expression in metastatic
      tumors compared to their matched primaries (P < .001). Individually, there was
      greater CAIX, PAX2, and PAX8 expression and lower RCCA expression in metastatic
      tumors. Most importantly, a significant proportion of originally RCCA-positive
      tumors lost such expression in metastases. CONCLUSIONS: Metastatic RCCs have
      significantly higher expression of PAX2 and PAX8 compared to primary RCCs. RCCA
      is not very reliable in this diagnostic setting, both because of its lower
      overall sensitivity and loss of expression in metastatic RCCs.

PMID- 23955464
TI  - Another laboratory test utilization program: our approach to reducing unnecessary
      1,25-dihydroxyvitamin D orders with a simple intervention.

PMID- 23955465
TI  - Granulocyte-colony stimulating factors as adjunctive therapy for diabetic foot
      infections.
AB  - BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) increases the release
      of neutrophil endothelial progenitor cells from the bone marrow and improves
      neutrophil functions, which are often impaired in people with diabetes.
      OBJECTIVES: To examine the effects of adjunctive G-CSF compared with placebo or
      no growth factor added to usual care on rates of infection, cure and wound
      healing in people with diabetes who have a foot infection. SEARCH METHODS: In
      March 2013, for this second update, we searched the Cochrane Wounds Group
      Specialised Register (searched 14 March 2013); the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 2); Ovid MEDLINE
      (1948 to March Week 1 2013); Ovid EMBASE (1974 to 2013 March 13); Ovid MEDLINE
      (In-Process march 13,2013); and EBSCO CINAHL (1982 to 28 February 2013).
      SELECTION CRITERIA: Randomised controlled trials (RCTs) that evaluated the effect
      of adding G-CSF to usual care in people with a diabetic foot infection. DATA
      COLLECTION AND ANALYSIS: Three review authors independently assessed trial
      eligibility, methodological quality and extracted data. We reported risk ratio
      (RR) or, for continuous outcomes, mean differences (MD), with 95% confidence
      intervals (CI). In the case of low or no heterogeneity we pooled studies using a
      fixed-effect model. MAIN RESULTS: We identified and included five eligible trials
      with a total of 167 patients. The investigators administered various G-CSF
      preparations, at different doses and for different durations of time. Adding G
      CSF did not significantly affect the likelihood of resolution of infection or
      wound healing, but it was associated with a significantly reduced likelihood of
      lower extremity surgical interventions (RR 0.38; 95 % CI 0.21 to 0.70), including
      amputation (RR 0.41; 95 % CI 0.18 to 0.95). Moreover, providing G-CSF reduced the
      duration of hospital stay (MD -1.40 days; 95% CI -2.27 to -0.53 days), but did
      not significantly affect the duration of systemic antibiotic therapy (MD -0.27
      days; 95% CI -1.30 to 0.77 days). AUTHORS' CONCLUSIONS: The available evidence is
      limited, but suggests that adjunctive G-CSF treatment in people with a diabetic
      foot infection, including infected ulcers, does not appear to increase the
      likelihood of resolution of infection or healing of the foot ulcer. However, it
      does appear to reduce the need for surgical interventions, especially
      amputations, and the duration of hospitalisation. Clinicians might consider
      adding G-CSF to the usual treatment of diabetic foot infections, especially in
      patients with a limb-threatening infection, but it is not clear which patients
      might benefit.

PMID- 23955466
TI  - Teaching about how doctors think: a longitudinal curriculum in cognitive bias and
      diagnostic error for residents.
AB  - BACKGROUND: Trends in medical education have reflected the patient safety
      movement's initial focus on systems. While the role of cognitive-based diagnostic
      errors has been increasingly recognised among safety experts, literature
      describing strategies to teach about this important problem is scarce. METHODS:
      48 PGY-2 internal medicine residents participated in a three-part, 1-year
      curriculum in cognitive bias and diagnostic error. Residents completed a multiple
      choice test designed to assess the recognition and knowledge of common heuristics
      and biases both before and after the curriculum. Results were compared with PGY-3
      residents who did not receive the curriculum. An additional assessment in which
      residents reviewed video vignettes of clinical scenarios with cognitive bias and
      debiasing techniques was embedded into the curriculum. RESULTS: 38 residents
      completed all three parts of the curriculum and completed all assessments.
      Performance on the 13-item multiple-choice knowledge test improved post
      curriculum when compared to both pre-curriculum performance (9.26 vs 8.26,
      p=0.002) and the PGY-3 comparator group (9.26 vs 7.69, p<0.001). All residents
      correctly identified at least one cognitive bias and proposed at least one
      debiasing strategy in response to the videos. CONCLUSIONS: A longitudinal
      curriculum in diagnostic error and cognitive bias improved internal medicine
      residents' knowledge and recognition of cognitive biases as measured by a novel
      assessment tool. Further study is needed to refine learner assessment tools and
      examine optimal strategies to teach clinical reasoning and cognitive bias
      avoidance strategies.

PMID- 23955467
TI  - When diagnostic testing leads to harm: a new outcomes-based approach for
      laboratory medicine.

PMID- 23955468
TI  - Effects of a team-based assessment and intervention on patient safety culture in
      general practice: an open randomised controlled trial.
AB  - BACKGROUND: The measurement of safety culture in healthcare is generally regarded
      as a first step towards improvement. Based on a self-assessment of safety
      culture, the Frankfurt Patient Safety Matrix (FraTrix) aims to enable healthcare
      teams to improve safety culture in their organisations. In this study we assessed
      the effects of FraTrix on safety culture in general practice. METHODS: We
      conducted an open randomised controlled trial in 60 general practices. FraTrix
      was applied over a period of 9 months during three facilitated team sessions in
      intervention practices. At baseline and after 12 months, scores were allocated
      for safety culture as expressed in practice structure and processes (indicators),
      in safety climate and in patient safety incident reporting. The primary outcome
      was the indicator error management. RESULTS: During the team sessions, practice
      teams reflected on their safety culture and decided on about 10 actions per
      practice to improve it. After 12 months, no significant differences were found
      between intervention and control groups in terms of error management (competing
      probability=0.48, 95% CI 0.34 to 0.63, p=0.823), 11 further patient safety
      culture indicators and safety climate scales. Intervention practices showed
      better reporting of patient safety incidents, reflected in a higher number of
      incident reports (mean (SD) 4.85 (4.94) vs 3.10 (5.42), p=0.045) and incident
      reports of higher quality (scoring 2.27 (1.93) vs 1.49 (1.67), p=0.038) than
      control practices. CONCLUSIONS: Applied as a team-based instrument to assess
      safety culture, FraTrix did not lead to measurable improvements in error
      management. Comparable studies with more positive results had less robust study
      designs. In future research, validated combined methods to measure safety culture
      will be required. In addition, more attention should be paid to evaluation of
      process parameters. Implemented actions and incident reporting may be more
      appropriate target endpoints. TRIAL REGISTRATION: German Clinical Trials Register
      (Deutsches Register Klinischer Studien, DRKS) No. DRKS00000145.

PMID- 23955469
TI  - Group B streptococci in milk and late neonatal infections: an analysis of cases
      in the literature.
AB  - BACKGROUND: The source for late-onset neonatal infections (LONI) due to group B
      Streptococcus (GBS) has not been fully explored. We reviewed GBS LONI cases
      associated with contaminated breast milk to determine whether breast milk was a
      possible route for neonatal infection. DATA SOURCES: A PubMed search from January
      1977 to March 2013 was performed with MeSH words "Streptococcus agalactiae",
      "group B Streptococcus", "infection", "milk", "human", "late-onset infection"
      and/or "neonate"; relevant cross references were also reviewed. RESULTS: Forty
      eight documented cases of GBS LONI matched our search criteria and were retrieved
      from the literature. When performed, molecular typing identified clonal isolates
      in the neonate and milk samples taken after LONI in all cases, with the
      hypervirulent sequence type 17 (ST-17) clone identified in two of these cases.
      Caesarean delivery combined with the absence of GBS recovery from maternal
      samples other than milk was noted for four cases. The rate of recurrent
      infections was high (35%) and, together with the data reviewed, points to a
      potential role of breast milk in GBS LONI. CONCLUSIONS: The cases reviewed here,
      together with the evidence of breast milk transmission for other pathogens,
      suggest that breast milk, which would account for repeated GBS transmission to
      the neonate, may favour gut translocation and subsequent LONI. Further
      investigations are nevertheless needed to study the relative importance of this
      contamination route compared with persistent postnatal gut colonisation and the
      dynamics of milk and neonatal gut colonisation.

PMID- 23955470
TI  - Biosynthetic polyesters consisting of 2-hydroxyalkanoic acids: current challenges
      and unresolved questions.
AB  - 2-Hydroxyalkanoates (2HAs) have become the new monomeric constituents of
      bacterial polyhydroxyalkanoates (PHAs). PHAs containing 2HA monomers, lactate
      (LA), glycolate (GL), and 2-hydroxybutyrate (2HB) can be synthesized by
      engineered microbes in which the broad substrate specificities of PHA synthase
      and propionyl-CoA transferase are critical factors for the incorporation of the
      monomers into the polymer chain. LA-based polymers, such as P[LA-co-3
      hydroxybutyrate (3HB)], have the properties of pliability and stretchiness which
      are distinctly different from those of the rigid poly(lactic acid) (PLA) and
      P(3HB) homopolymers. This versatile platform is also applicable to the
      biosynthesis of GL- and 2HB-based polymers. In the case of the synthesis of 2HB
      based polymers, the enantiospecificity of PHA synthase enabled the production of
      isotactic (R)-2HB-based polymers, including P[(R)-2HB], from racemic precursors
      of 2HB. P(2HB) is a pliable material, in contrast to PLA. Furthermore, to obtain
      a new 2HA-polymerizing PHA synthase, the class I PHA synthase from Ralstonia
      eutropha was engineered so as to achieve the first incorporation of LA units. The
      analysis of the polymer synthesized using this new LA-polymerizing PHA synthase
      unexpectedly focused a spotlight on the studies on block copolymer biosynthesis. 

PMID- 23955471
TI  - Evaluation of solid polymeric organic materials for use in bioreactive sediment
      capping to stimulate the degradation of chlorinated aliphatic hydrocarbons.
AB  - In situ bioreactive capping is a promising technology for mitigation of surface
      water contamination by discharging polluted groundwater. Organohalide respiration
      (OHR) of chlorinated ethenes in bioreactive caps can be stimulated through
      incorporation of solid polymeric organic materials (SPOMs) that provide a
      sustainable electron source for organohalide respiring bacteria. In this study,
      wood chips, hay, straw, tree bark and shrimp waste, were assessed for their long
      term applicability as an electron donor for OHR of cis-dichloroethene (cDCE) and
      vinyl chloride (VC) in sediment microcosms. The initial release of fermentation
      products, such as acetate, propionate and butyrate led to the onset of extensive
      methane production especially in microcosms amended with shrimp waste, straw and
      hay, while no considerable stimulation of VC dechlorination was obtained in any
      of the SPOM amended microcosms. However, in the longer term, short chain fatty
      acids accumulation decreased as well as methanogenesis, whereas high
      dechlorination rates of VC and cDCE were established with concomitant increase of
      Dehalococcoides mccartyi and vcrA and bvcA gene numbers both in the sediment and
      on the SPOMs. A numeric simulation indicated that a capping layer of 40 cm with
      hay, straw, tree bark or shrimp waste is suffice to reduce the groundwater VC
      concentration below the threshold level of 5 MUg/l before discharging into the
      Zenne River, Belgium. Of all SPOMs, the persistent colonization of tree bark by
      D. mccartyi combined with the lowest stimulation of methanogenesis singled out
      tree bark as a long-term electron donor for OHR of cDCE/VC in bioreactive caps. 

PMID- 23955472
TI  - Extraordinary denaturant tolerance of keratinolytic protease complex assemblies
      produced by Meiothermus ruber H328.
AB  - A moderately thermophilic bacterial strain, Meiothermus ruber H328, can
      efficiently solubilize intact chicken feathers by aerobic cultivation at 55 
      degrees C for 6 days. The keratinolytic proteases extracellularly secreted by the
      strain were partially purified by an ultrafiltration system and a size-exclusion
      column chromatography, and thus were found to be two different sizes of
      macromolecules with an extremely high molecular mass like the sizes of virus and
      DNA (peak 1 fraction) and with a molecular mass of larger than 500 kDa (peak 2
      fraction). They formed protein complex assemblies that were composed of multiple
      but different proteins. The peak 1 fraction showed more thermophilic
      characteristics than did the peak 2 fraction in temperature dependence and
      thermal stability. By contrast, they comparably showed extraordinary resistance
      to powerful denaturants, SDS at 30 % (w/v) and organic solvents (methanol,
      ethanol, acetonitrile, acetone, and chloroform) at 40 % (v/v) at 60  degrees C
      for 30 min. The extraordinary denaturant tolerance and the large molecular size
      of the keratinolytic protease complex assemblies suggest the possibility that
      those may be lipophilic and have the structure of partial membrane fractions, or
      membrane vesicles, which are exfoliated from the outer membrane of the cells.

PMID- 23955473
TI  - A novel cholesterol-producing Pichia pastoris strain is an ideal host for
      functional expression of human Na,K-ATPase alpha3beta1 isoform.
AB  - The heterologous expression of mammalian membrane proteins in lower eukaryotes is
      often hampered by aberrant protein localization, structure, and function, leading
      to enhanced degradation and, thus, low expression levels. Substantial quantities
      of functional membrane proteins are necessary to elucidate their structure
      function relationships. Na,K-ATPases are integral, human membrane proteins that
      specifically interact with cholesterol and phospholipids, ensuring protein
      stability and enhancing ion transport activity. In this study, we present a
      Pichia pastoris strain which was engineered in its sterol pathway towards the
      synthesis of cholesterol instead of ergosterol to foster the functional
      expression of human membrane proteins. Western blot analyses revealed that
      cholesterol-producing yeast formed enhanced and stable levels of human Na,K
      ATPase alpha3beta1 isoform. ATPase activity assays suggested that this Na,K
      ATPase isoform was functionally expressed in the plasma membrane. Moreover,
      [(3)H]-ouabain cell surface-binding studies underscored that the Na,K-ATPase was
      present in high numbers at the cell surface, surpassing reported expression
      strains severalfold. This provides evidence that the humanized sterol composition
      positively influenced Na,K-ATPase alpha3beta1 stability, activity, and
      localization to the yeast plasma membrane. Prospectively, cholesterol-producing
      yeast will have high potential for functional expression of many mammalian
      membrane proteins. 

PMID- 23955474
TI  - Response of chickpea genotypes to Agrobacterium-mediated delivery of Chickpea
      chlorotic dwarf virus (CpCDV) genome and identification of resistance source.
AB  - Chickpea stunt disease caused by Chickpea chlorotic dwarf virus (CpCDV) (genus
      Mastrevirus, family Geminiviridae) is the most important biotic stress affecting
      chickpea crops worldwide. A survey conducted on the incidence of stunt disease
      clearly revealed high incidence of the disease with severe symptom expression in
      both indigenous and imported genotypes. To manage the disease in a sustainable
      way, resistant genotypes need to be bred by adopting objective and precise
      assessment of the disease response of chickpea genotypes. At present, evaluation
      of CpCDV resistance is conducted on the basis of natural infection in the field,
      which is bound to be erroneous due to vagaries in vector population. To
      circumvent the above problems, we devised an agroinoculation technique that
      involves the delivery of viral genomic DNA through Agrobacterium tumefaciens. An
      objective scoring system assigning quantitative value to different symptoms has
      been evolved to assess the response of chickpea genotypes to CpCDV inoculation.
      Using the inoculation and scoring techniques, we screened 70 genotypes, which
      helped in differentiating field resistance that is more due to resistance to
      vector feeding than resistance to the virus.

PMID- 23955475
TI  - Importance of codB for new codA-based markerless gene deletion in Gluconobacter
      strains.
AB  - For the detailed molecular analysis, genomic modification, and application of
      acetic acid bacteria such as Gluconobacter in biotechnological processes, a
      simple markerless deletion system is essential. The available methods have either
      low efficiencies or their applicability is restricted to strains containing an
      upp mutation. We now developed a method based on counterselection by cytosine
      deaminase, encoded by the codA gene from Escherichia coli, in the presence of the
      fluorinated pyrimidine analogue 5-fluorocytosine (FC). The codA-encoded enzyme
      converts nontoxic FC to toxic 5-fluorouracil, which is channeled into the
      metabolism by the uracil phosphoribosyltransferase, encoded by the chromosomal
      upp gene of Gluconobacter. We found that the presence of E. coli codB, encoding a
      cytosine permease, was needed for a high efficiency of gene deletion. The system
      is applicable in wild-type strains because no preceding deletions are required.
      Based on the fact that a codA gene is absent and an upp gene is present in almost
      all acetic acid bacteria sequenced so far, the method should also be applicable
      for other genera of the Acetobacteraceae. 

PMID- 23955476
TI  - Multiparametric optical coherence tomography imaging of the inner retinal
      hemodynamic response to visual stimulation.
AB  - The hemodynamic response to neuronal activation is a well-studied phenomenon in
      the brain, due to the prevalence of functional magnetic resonance imaging. The
      retina represents an optically accessible platform for studying lamina-specific
      neurovascular coupling in the central nervous system; however, due to
      methodological limitations, this has been challenging to date. We demonstrate
      techniques for the imaging of visual stimulus-evoked hyperemia in the rat inner
      retina using Doppler optical coherence tomography (OCT) and OCT angiography.
      Volumetric imaging with three-dimensional motion correction, en face flow
      calculation, and normalization of dynamic signal to static signal are techniques
      that reduce spurious changes caused by motion. We anticipate that OCT imaging of
      retinal functional hyperemia may yield viable biomarkers in diseases, such as
      diabetic retinopathy, where the neurovascular unit may be impaired.

PMID- 23955477
TI  - Intra-abdominal desmoid tumor difficult to distinguish from a gastrointestinal
      stromal tumor: report of two cases.
AB  - Desmoid tumors are benign fibroblastic neoplasms with no metastatic potential,
      but a propensity for local recurrence even after complete surgical resection.
      These lesions can develop at any site in the body, and commonly occur in the
      intra-abdominal area. Intra-abdominal desmoid tumors usually occur at the
      mesentery or retroperitoneum, and may morphologically mimic gastrointestinal
      stromal tumors (GISTs). Distinguishing between these tumors is important, because
      the therapies differ substantially, but is often difficult even with the use of
      CD117 staining. We herein report the cases of two patients with sporadic intra
      abdominal desmoid tumors that were differentiated from GIST by immunohistological
      examination using beta-catenin and CD34. Desmoid tumors specifically express
      nuclear beta-catenin, and show no expression of CD34. We recommend staining for
      beta-catenin and CD34 when an intra-abdominal desmoid tumor is suspected. 

PMID- 23955478
TI  - Anastomotic stenosis of the descending colon caused by barium granuloma formation
      following barium peritonitis: report of a case.
AB  - Anastomotic stricture reportedly often recurs following barium peritonitis,
      regardless of whether the anastomotic diameter is initially sufficient. However,
      the causes of repetitive stricture have not been clarified. We report a case that
      suggests the pathophysiology of recurrent anastomotic strictures following barium
      peritonitis. The patient was a 39-year-old Japanese man with idiopathic
      perforation of the descending colon after undergoing an upper gastrointestinal
      barium contrast study. After emergency peritoneal lavage and diverting colostomy,
      created using the perforated region, the patient recovered uneventfully and 3
      months later, the colostomy was closed and the perforated colon was resected.
      However, 7 months after colostomy closure, abdominal distention gradually
      developed, and colonoscopy revealed an anastomotic stricture. The patient was
      referred to our hospital where he underwent resection of the anastomotic
      stricture. The surgical specimen exhibited barium granulomas not only in the
      subserosa of the entire specimen, but also in the submucosa and lamina propria
      localized in the anastomotic site. These findings suggest that barium was
      embedded in the submucosa and lamina propria with manipulation of the stapled
      anastomosis and that the barium trapped in the anastomotic site caused persistent
      inflammation, resulting in an anastomotic stricture.

PMID- 23955479
TI  - Influence of fludarabine on the pharmacokinetics of oral busulfan during
      pretransplant conditioning for hematopoietic stem cell transplantation.
AB  - This study evaluated the influence of fludarabine on the pharmacokinetics of
      busulfan administered orally to patients receiving a conditioning regimen for
      hematopoietic allogeneic stem cell transplantation (HSCT). Twenty-six patients
      treated with oral busulfan (1 mg/kg/6 h for 4 days) were divided into two groups
      according to the concomitant administration of fludarabine (n = 11; 30 mg/m(2)
      for 5 days) or subsequent administration of cyclophosphamide (n = 15; 60 mg/kg
      for 2 days). Serial blood samples were collected on Day 4 of busulfan
      administration. Plasma busulfan concentrations were determined by HPLC-UV and the
      pharmacokinetic parameters were calculated using the WinNonlin program. Patients
      concomitantly treated with fludarabine showed reduced apparent clearance of
      busulfan (110.5 mL/h/kg vs. 157.4 mL/h/kg) and higher AUC0-6 (area under the
      plasma concentrations vs. time curve) than patients subsequently treated with
      cyclophosphamide (7.9 ug h/mL vs. 5.7 ug h/mL). No association was observed
      between busulfan AUC0-6 and clinical evolution of the patients. Although plasma
      busulfan concentrations were higher in patients receiving concomitant
      fludarabine, myelosuppression-related toxicity was less frequent than in patients
      treated with busulfan and cyclophosphamide. The results suggest that patients
      treated with fludarabine should receive 30% lower busulfan doses during
      conditioning protocols for HSCT. 

PMID- 23955480
TI  - Recent progress in research on the distribution and function of NUCB2/nesfatin-1
      in peripheral tissues.
AB  - Nesfatin-1 is a polypeptide derived from the posttranslational processing of the
      N-terminal fragment of nucleobindin 2 (NUCB2), that was originally identified as
      an anorexigenic hypothalamic neuropeptide. A number of reports have recently
      shown that NUCB2/nesfatin-1 is widely expressed in various peripheral tissues,
      including those of the gastrointestinal tract where it may participate in various
      pathophysiological processes. One of its roles may be regulation of energy
      homeostasis. As a result, nesfatin-1 may be a novel target for exploring the
      underlying mechanisms and the treatment of metabolic syndromes.

PMID- 23955481
TI  - Scaling laws for van der Waals interactions in nanostructured materials.
AB  - Van der Waals interactions have a fundamental role in biology, physics and
      chemistry, in particular in the self-assembly and the ensuing function of
      nanostructured materials. Here we utilize an efficient microscopic method to
      demonstrate that van der Waals interactions in nanomaterials act at distances
      greater than typically assumed, and can be characterized by different scaling
      laws depending on the dimensionality and size of the system. Specifically, we
      study the behaviour of van der Waals interactions in single-layer and multilayer
      graphene, fullerenes of varying size, single-wall carbon nanotubes and graphene
      nanoribbons. As a function of nanostructure size, the van der Waals coefficients
      follow unusual trends for all of the considered systems, and deviate
      significantly from the conventionally employed pairwise-additive picture. We
      propose that the peculiar van der Waals interactions in nanostructured materials
      could be exploited to control their self-assembly. 

PMID- 23955482
TI  - Dietary selenium supplementation and whole blood gene expression in healthy North
      American men.
AB  - Selenium (Se) is a trace nutrient required in microgram amounts, with a
      recommended dietary allowance of 55 MUg/day in humans. The nutritional functions
      of Se are performed by a group of 25 selenoproteins containing the unusual amino
      acid selenocysteine at their active sites. The selenoproteins with known
      activities are oxidation-reduction enzymes with roles in antioxidant protection,
      redox homeostasis and signaling, and thyroid hormone metabolism. Both
      deficiencies and excesses of Se are associated with impaired innate and adaptive
      immune responses. We supplemented 16 healthy men for 1 year with 300 MUg Se/day
      as high-Se yeast or placebo yeast and measured whole blood gene expression with
      DNA microarrays before and after supplementation. Protein phosphorylation was the
      main biological process in common among the Se-responsive genes, which included a
      prominent cluster of protein kinases, suggesting that protein phosphorylation in
      leukocytes is sensitive to Se supplementation. We found highly ranked clusters of
      genes associated with RNA processing and protein transport, suggesting that
      dietary Se may regulate protein expression in leukocytes at both the
      posttranscriptional and posttranslational levels. The main functional pathway
      affected by Se supplementation was FAS apoptosis signaling, and expression of
      genes associated with T cell and natural killer cell cytotoxicity was increased.
      At the same time, the numbers of circulating natural killer and T cells
      expressing activation markers decreased. These changes are consistent with an
      anti-inflammatory effect of Se supplementation exerted through regulation of
      protein phosphorylation.

PMID- 23955483
TI  - Dietary nickel chloride restrains the development of small intestine in broilers.
AB  - The aim of this study was to determine the effects of dietary NiCl2 on the
      development of the small intestine in broilers by the methods of light
      microscopy, histochemistry and enzyme-linked immunosorbent assay. A total of 240
      one-day-old avian broilers were divided into four groups and fed on a corn
      soybean basal diet or the same basal diet supplemented with 300, 600 and 900
      mg/kg of nickel chloride (NiCl2) for 42 days. Results showed that the small
      intestinal villus height, crypt depth and villus/crypt ratio were significantly
      decreased, and also the small intestinal goblet cells numbers and insulin-like
      growth factor-1 (IGF-1) and epidermal growth factor (EGF) contents were
      significantly decreased in the 300-, 600- and 900-mg/kg groups when compared with
      those of the control group. In conclusion, dietary NiCl2 in excess of 300 mg/kg
      reduced the villus height, crypt depth, the goblet cells population and the IGF-1
      and EGF contents in the small intestine, indicating that the normal development
      and function of the small intestine were finally impaired in broilers. This study
      firstly provided the new experimental information for future studies on the
      effects of NiCl2 on the intestinal function in humans and other animals.

PMID- 23955484
TI  - Effects of high dietary fluorine on erythrocytes and erythrocyte immune adherence
      function in broiler chickens.
AB  - Fluoride can exert toxic effects on soft tissues, giving rise to a broad array of
      symptoms and pathological changes. The aim of this study was to investigate on
      erythrocytes and erythrocyte immune adherence function in broiler chickens fed
      with high fluorine (F) diets by measuring the total erythrocyte count (TEC), the
      contents of hemoglobin (Hb), packed cell volumn (PCV), erythrocyte osmotic
      fragility (EOF), erythrocyte C3b receptor rosette rate (E-C3bRR), and erythrocyte
      immune complex rosette rate (E-ICRR). A total of 280 1-day-old healthy avian
      broiler chickens were randomly allotted into four equal groups of 70 birds each
      and fed with a corn-soybean basal diet containing 22.6 mg F/kg (control group) or
      same basal diets supplemented with 400, 800, and 1,200 mg F/kg (high F groups I,
      II, and III) in the form of sodium fluoride for 42 days. Blood samples were
      collected for the abovementioned parameters analysis at 14, 28, and 42 days of
      age during the experiment. The experimental results indicated that TEC, Hb, and
      PCV were significantly lower (p < 0.05 or p < 0.01), and EOF was higher (p < 0.05
      or p < 0.01) in the high F groups II and III than that in the control group from
      14 to 42 days of age. The E-C3bRR was significantly decreased (p < 0.01) in the
      three high F groups, whereas the E-ICRR was markedly increased (p < 0.01) in the
      high F groups II and III from 14 to 42 days of age. It was concluded that dietary
      F in the range of 800 to 1, 200 mg/kg could significantly cause anemia and impair
      the integrity of erythrocyte membrane, the transport capacity of oxygen and
      carbon dioxide, and erythrocyte immune adherence function in broiler chickens.

PMID- 23955485
TI  - Bubbles in the heart as first sign of gastric pneumatosis.
AB  - This case report describes a 5-week-old boy with an unusual presentation of
      gastric pneumatosis caused by suspected necrotizing enterocolitis (NEC) after
      cardiogenic shock. Postnatally, a pulmonary atresia with intact ventricular
      septum was supplied by a modified Blalock-Taussig shunt. On transthoracic
      echocardiography in week 5, primarily performed to rule out pericardial effusion,
      air bubbles have been apparent in the right atrium. Intracardiac air found on
      echocardiogram is generally associated with an indwelling venous catheter but-as
      exemplified by this case report-may also occur in the setting of NEC. An
      abdominal radiograph showed an isolated gastric pneumatosis, which is an unusual
      location of NEC. It is speculated that air moved through the connecting veins to
      the right atrium, the pneumatosis located in the gastric wall being a
      prerequisite to this pathophysiology. CONCLUSION: The suspected NEC was located
      in the stomach enabling the intramural air to pass through connecting veins to
      the right atrium. The first specific sign of NEC in our case was air bubbles in
      the right atrium on echocardiography.

PMID- 23955486
TI  - Characteristics of Kikuchi-Fujimoto disease in children compared with adults.
AB  - Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting disease characterized
      by cervical lymphadenopathy. Although it was primarily thought to be a disease of
      young adults, it has been increasingly recognized in children. To define the
      characteristics of KFD in children, we reviewed the medical records of patients
      younger than 18 years of age who were diagnosed with KFD from 2001 to 2012 at
      Korea University Medical Center, as well as worldwide published reports of KFD. A
      total of 140 pediatric patients and 733 patients of all ages was analyzed.
      Compared to the female predominance found in adults (2:1), young boys were more
      commonly affected than young girls (1.4:1). Cervical lymphadenopathy was the most
      common clinical finding in children, as it was in adults. Lymphadenopathy was
      more likely to be tender (69 vs. 44 %, p < 0.001) but less generalized (1 vs. 8
      %, p < 0.05) in children compared to adults. Fever (82 vs. 35 %, p < 0.001) and
      rash (10 vs. 4 %, p < 0.05) were observed in children more commonly than in
      adults. Leukopenia was observed in 50 and 38 % of children and adults,
      respectively. Rates of recurrence and association with autoimmune diseases in
      children were comparable to those of adults. Cervical lymphadenopathy was the
      most common clinical manifestation of KFD in all ages. While fever and rash were
      more common in children with KFD compared to adults, generalized lymphadenopathy
      was rarer. 

PMID- 23955487
TI  - Accuracy of transcutaneous bilirubin measurement in preterm low-birth-weight
      neonates.
AB  - The objective of this study was to evaluate the correlation and agreement between
      transcutaneous and serum bilirubin among preterm low-birth-weight neonates.
      Neonates born at <35 weeks of gestation with birth weight <2,000 g were enrolled
      prospectively. Transcutaneous bilirubin (TcB) was measured at forehead, sternum,
      and abdomen at 24 +/- 6 and 72 +/- 12 h after birth and when icterus involved
      arms or legs (Kramer zone 4-5). Serum total bilirubin (STB) was measured by
      microbilimeter (STB-M) at all these time-points and by high-performance liquid
      chromatography (STB-H) at one randomly chosen time-point. A total of 1,619
      observations were made in 256 neonates (median gestation, 34 weeks (IQR, 32-35),
      birth weight 1,522 +/- 288 g). Overall there was excellent correlation and
      agreement between TcB and STB-M with TcB on forehead being most accurate (r =
      0.84, mean difference, 0.3 +/- 1.9 mg/dL) followed by TcB on abdomen (r = 0.73,
      mean difference, 1.5 +/- 2.6 mg/dL) and sternum (r = 0.72, mean difference, 1.5
      +/- 2.6 mg/dL). TcB performed well at all three points of measurement with best
      correlations being observed at icterus level 4/5. Correlation between TcB and STB
      H measured by high-performance liquid chromatography was less strong but
      significant (r = 0.59 to 0.69 at different time points of measurement).
      CONCLUSIONS: TcB has good correlation and agreement with STB in preterm low-birth
      weight neonates born at >=28 weeks of gestation.

PMID- 23955488
TI  - Is pro-adrenomedullin a more useful marker in hospitalized infants with sepsis?

PMID- 23955489
TI  - Exogenous and endogenous therapeutic effects of combination Sodium Ferulate and
      bone marrow stromal cells (BMSCs) treatment enhance neurogenesis after rat focal
      cerebral ischemia.
AB  - Combining bone marrow stromal cells (BMSCs) with pharmacological therapy is an
      attractive approach for neurological function recovery of stroke. Our previous
      reports demonstrated that Sodium Ferulate (SF) combined with BMSCs administration
      could facilitate BMSCs migration into the ischemic brain by up-regulation of
      stromal cell-derived factor-1 alpha (SDF-1alpha)/chemokine (CXC motif) receptor-4
      axis after stroke. To further investigate whether combination treatment could
      enhance neurogenesis through exogenous and endogenous therapeutic effects, we
      established rat permanent middle cerebral artery occlusion (pMCAo) model and
      measured ischemic infarct size by magnetic resonance imaging (MRI) scanning in
      the present study. The results showed that combination treatment could
      dramatically reduce ischemic infarction size which may be attributed to the
      effects on decreasing brain edema and enhancing cerebral tissue perfusion at 3
      days after stroke. Immunofluorescence staining results indicated that combination
      treatment could not only promote expression of Glucose transporter 1(Glut1) and
      Neuron-specific class III beta-tubulin (Tuj1) in the periinfarct area, but also
      improve BMSCs expression of Glut1, GFAP and Tuj1. Moreover, it showed combination
      treatment could enhance the endogenous expression of Tuj-1 in ischemic boundary
      zone. These results perhaps associated with combination treatment up-regulating
      bone morphogenetic proteins (BMP)2/4 expressions and down-regulating Notch-1,
      Hes1 and Hes5 expressions as detected by Western Blot analysis. Our study firstly
      demonstrated in vivo that combination treatment could facilitate exogenous BMSCs
      differentiation into neural-and astrocytic-like cells, as well as enhance repair
      capacity of brain parenchymal cells by promoting glucose metabolism and
      endogenous neurogenesis after stroke. These results illustrate that
      administration of SF and BMSCs is a potential pathway of cell-based
      pharmacological treatment towards ischemic stroke. 

PMID- 23955490
TI  - Assessment of the feasibility of a rehabilitation intervention program for breast
      cancer survivors with cognitive complaints.
AB  - To assess the feasibility of a cognitive rehabilitation program in breast cancer
      survivors (BCS) with persistent post-treatment cognitive complaints. BCS with
      cognitive complaints, 18-months to 5-years post-treatment, were recruited for a
      once-weekly, five-week, group cognitive training intervention. Outcome measures
      included self-reported mood and cognitive function, and neurocognitive tests
      administered at pre-intervention, immediate-, two-month and four-month post
      intervention. A sub-study in eight participants evaluated resting state
      quantitative electroencephalography (qEEG) changes from pre- to immediate post
      intervention in relationship to post-intervention changes in cognitive
      complaints. Twenty-seven BCS completed the protocol and tolerated the
      intervention well. We observed significant reductions in total and memory
      specific cognitive complaints from pre-intervention to immediate post
      intervention (p = 0.031 and p = 0.009, respectively) and at four-months post
      intervention (p < 0.0001 and p < 0.001, respectively). Significant improvement in
      neurocognitive tests were found for Symbol Digit, Stroop, and Trails A tests (df
      = 26, all p's <0.05). Effect sizes for changes from pre-intervention to immediate
      and to four-month post intervention ranged from 0.429 to 0.607, and from 0.439 to
      0.741, respectively. Increase in qEEG absolute alpha power over the course of the
      intervention was associated with reduced complaints at immediate post
      intervention (r = -0.78, p = 0.021), two-months (r range = -0.76 to -0.82, p
      value range 0.004 to 0.03), and four-months (r = -0.71, p = 0.048). A five-week
      group cognitive training intervention is feasible and well tolerated. Cognitive
      complaints and neurocognitive test performances showed positive changes. qEEG may
      serve as a potential biomarker for improvement in self-reported complaints. A
      randomized clinical trial is underway to test the efficacy of the intervention. 

PMID- 23955491
TI  - Application of proton magnetic resonance spectroscopy on substantia nigra
      metabolites in Parkinson's disease.
AB  - This study investigates changes in substantia nigra metabolites in Parkinson's
      disease (PD) using proton magnetic resonance spectroscopy ((1)H- MRS). Thirty
      patients with asymmetric PD and 20 normal controls were included in this study.
      Substantia nigra metabolites were detected in all subjects using 3D-multimer (1)H
      MRS with a 3.0 T MRI scanner. The relative ratios of NAA/Cr, NAA/Cho, NAA/(Cho +
      Cr) in the substantia nigra were compared between two sides of asymmetric PD
      patients as well as between PD patients and controls. Significant differences in
      NAA/Cr, NAA/Cho, NAA/(Cho + Cr) were observed between PD patients and healthy
      controls (P < 0.05) as well as between the ipsilateral and contralateral of
      affected extremity in PD patients (P < 0.05). Significant differences in NAA/Cr,
      NAA/Cho, NAA/(Cho + Cr) were also observed between patients with mild and severe
      PD. Thus, we found that (1)H-MRS can be used to detect substantia nigra
      metabolites in PD patients, which may be useful for early diagnosis and
      evaluation of PD. 

PMID- 23955492
TI  - Brain responses to erotic and other emotional stimuli in breast cancer survivors
      with and without distress about low sexual desire: a preliminary fMRI study.
AB  - Many breast cancer survivors report a loss of sexual desire and arousability,
      consonant with the new DSM-V category of female sexual interest/arousal disorder.
      The cause of decreased sexual desire and pleasure after treatment for cancer is
      unknown. One possibility is that cancer, or treatment for cancer, damages brain
      circuits that are involved in reward-seeking. To test the hypothesis that brain
      reward systems are involved in decreased sexual desire in breast cancer
      survivors, we used functional magnetic resonance imaging (fMRI) to compare brain
      responses to erotica and other emotional stimuli in two groups of women
      previously treated for breast cancer with chemotherapy: those who were distressed
      about a perceived loss of sexual desire and those who may have had low desire,
      but were not distressed about it. Women distressed about their desire had reduced
      brain responses to erotica in the anterior cingulate and dorsolateral prefrontal
      cortex, which are part of the brain reward system. This study is the first to
      demonstrate, in cancer survivors, that problems with sexual desire/arousability
      are associated with blunted brain responses to erotica in reward systems. Future
      research is necessary to determine whether brain responses differ as a result of
      chemotherapy, hormone therapy, and menopausal status. This may contribute to the
      development of new, evidence-based interventions for one of the most prevalent
      and enduring side effects of cancer treatment. 

PMID- 23955493
TI  - H-loop histidine catalyzes ATP hydrolysis in the E. coli ABC-transporter HlyB.
AB  - Adenosine triphosphate (ATP)-binding cassette (ABC) transporters form a family of
      molecular motor proteins that couple ATP hydrolysis to substrate translocation
      across cell membranes. Each nucleotide binding domain of ABC-transporters
      contains a highly conserved H-loop histidine residue, whose precise mechanistic
      role in motor functions has remained elusive. By using combined quantum
      mechanical and molecular mechanical (QM/MM) calculations, we showed that the
      conserved H-loop residue H662 in E. coli HlyB, a bacterial ABC-transporter, can
      act first as a general acid and then as a general base to facilitate proton
      transfer in ATP hydrolysis. Without the assistance of H662, direct proton
      transfer from the lytic water to ATP results in a substantially higher barrier
      height. Our findings suggest that the essential function of the H-loop residue
      H662 is to provide a "chemical linchpin" that shuttles protons between reactants
      through a relay mechanism, thereby catalyzing ATP hydrolysis in HlyB. 

PMID- 23955495
TI  - Effects of light on the circadian rhythm of diabetic rats under restricted
      feeding.
AB  - The aim of this study was to investigate whether the entrainment of light cue is
      affected or not in diabetic animals. We found that the individual light/dark (LD)
      reversal showed a tissue- and gene-specific effect on the circadian phases of
      peripheral clock genes, which was generally similar between the control and
      diabetic rats. In the liver and heart, the peak phases of examined clock genes
      (Bmal1, Rev-erbalpha, Per1, and Per2) were slightly shifted by 0~4 h in the liver
      and heart of control and diabetic rats. However, we found that the peak phases of
      these clock genes were greatly shifted by 8~12 h after the LD reversal for 7 days
      in the pineal gland of both control and diabetic rats. However, the activity
      rhythm was greatly different between two groups. After the individual LD
      reversal, the activity rhythm was completely shifted in the control rats but
      retained in the diabetic rats. These observations suggested that the behavioral
      rhythm of diabetic rats may be uncoupled from the master clock after the
      individual LD reversal. Moreover, we also found that the serum glucose levels of
      diabetic rats kept equally high throughout the whole day without any shift of
      peak phase after the individual reversal of LD cycle. While the serum glucose
      levels of control rats were tightly controlled during the normal and LD reversal
      conditions. Thus, the impaired insulin secretion induced uncontrollable serum
      glucose level may result in uncoupled activity rhythm in the diabetic rats after
      the individual LD reversal.

PMID- 23955496
TI  - Evaluation of long-term trends in hydrographic and nutrient parameters in a
      southeast US coastal river.
AB  - The Nassau River estuary is located in northeast Florida adjacent to the
      eutrophic St. Johns River. Historically, development has been sparse in the
      Nassau River's catchment; thus, the system may provide a relatively undisturbed
      aquatic environment. To monitor the condition of the Nassau River estuary and to
      discern spatial and temporal trends in water quality, nutrients and hydrographic
      variables were assessed throughout the estuary from 1997 to 2011. Hydrographic
      (temperature, salinity, total suspended solids, and turbidity) and nutrient
      parameters (total phosphorus, ortho-PO4(3-), total nitrogen, NH4(+), total
      Kjeldahl nitrogen, and NO3(-)) were monitored bimonthly at 12 sites in the
      mesohaline and polyhaline zones of the river. Nonparametric Kendall's Tau was
      implemented to analyze long-term water quality patterns. Salinity was found to
      increase with time, particularly in the mesohaline sampling sites. Dissolved
      oxygen decreased over time in the estuary and hypoxic conditions became
      increasingly frequent in the final years of the study. Nutrients increased in the
      estuary, ranging from 149 to 401%. Rainfall data collected in adjacent
      conservation areas did not correlate well with nutrients as compared with stream
      discharge data collected in the basin headwaters, outside of the conservation
      lands, attributed here to expanding urbanization. During the study period, the
      Nassau basin underwent rapid human population growth and land development
      resulting in commensurate impacts to water quality. Nutrient and physical data
      collected during this study indicate that the Nassau River estuary is becoming
      more eutrophic with time.

PMID- 23955497
TI  - Selection of a halophytic plant for assessing the phytotoxicity of dredged
      seaport sediment stored on land.
AB  - The filling of dry quarries in coastal areas with sediments dredged in seaports
      represents a potentially interesting method of recycling of these materials.
      However, this recycling requires the prior carrying out of an Environmental Risk
      Assessment of the scenario concerned. For this, the question arose as to the type
      of plants capable of developing on the surface of such a deposit and the method
      to implement for assessing the possible phytotoxicity of dredged sediments. To
      answer this question, we chose to work with halophytic plants to be free from the
      salt-related effect and to assess only the effect related to the toxic compounds
      present. Based on the objectives set, these works led to the use of common plants
      of the French coast, with direct seeding, and with pollution-sensitive plants.
      Three species of angiosperms, Armeria maritima, Anthemis maritima and Plantago
      coronopus, were finally tested. As a result of this work, Armeria maritima was
      retained as the most suitable plant for testing the possible phytotoxic effect of
      dredged marine sediments stored on land. The results obtained with this plant are
      as follows: germination of 40 % of the seeds in 31 days, produced biomass of 493
      mg FW in 6 months and a capacity to bioaccumulate metal pollutants in roots with
      350 and 720 mg/kg DW for Zn and Cu, respectively. 

PMID- 23955498
TI  - Consistency of defoliation data of the national training courses for the forest
      condition survey in Germany from 1992 to 2012.
AB  - The consistency of visual assessment of tree defoliation, which represents the
      most widely used indicator for tree condition, has frequently been in the focus
      of scientific criticism. Thus, the objective of the present study was to examine
      the consistency of the defoliation data from the annual national training courses
      for the forest condition survey in Germany from 1992 to 2012. Defoliation
      assessments were carried out in stands of beech (Fagus sylvatica), oak (Quercus
      robur and Quercus petraea), Norway spruce (Picea abies), and pine (Pinus
      sylvestris). Among the observer teams, the absolute deviation from the observer
      mean of all years was +/-4.4 % defoliation and the standard deviation of
      defoliation was +/-5.5 %. On average, 94 % of the assessments were located within
      the +/-10 % interval of deviation from the mean. Tree species-specific
      differences did not occur when all years were considered. A trend towards
      increasing consistency was observed from 1992 to 2012, in particular for oak and
      spruce. The deviation of defoliation assessments depended non-linearly on the
      level of defoliation with highest deviations at intermediate defoliations. In
      spite of high correlations and agreements among observers, systematic errors were
      determined in nearly every year. However, within-observer variances were higher
      than between-observer variances. The present study applied a three-way evaluation
      approach for the assessment of consistency and demonstrated that the visual
      defoliation assessment at the national training courses in general produced
      consistent data within Germany from 1992 to 2012. 

PMID- 23955500
TI  - Molecular characterization and phylogenetic analysis of new variants of the
      porcine epidemic diarrhea virus in Gansu, China in 2012.
AB  - Between January 2012 and March 2012, the infection rates of porcine epidemic
      diarrhea virus (PEDV) increased substantially in vaccinated swine herds in many
      porcine farms in Gansu Province, China. The spike (S) glycoprotein is an
      important determinant for PEDV biological properties. To determine the
      distribution profile of PEDV outbreak strains, we sequenced the full-length S
      gene of five samples from two farms where animals exhibited severe diarrhea and
      high mortality rates. Five new PEDV variants were identified, and the molecular
      diversity, phylogenetic relationships, and antigenicity analysis of Gansu field
      samples with other PEDV reference strains were investigated. A series of
      insertions, deletions, and mutations in the S gene was found in five PEDV
      variants compared with classical and vaccine strains. These mutations may provide
      stronger pathogenicity and antigenicity to the new PEDV variants that influenced
      the effectiveness of the CV777-based vaccine. Our results suggest that these new
      PEDV variant strains in Gansu Province might be from South Korean or South China,
      and the effectiveness of the CV777-based vaccine needs to be evaluated. 

PMID- 23955501
TI  - A polytropic caprine arthritis encephalitis virus promoter isolated from multiple
      tissues from a sheep with multisystemic lentivirus-associated inflammatory
      disease.
AB  - Caprine arthritis encephalitis virus (CAEV) is a lentivirus that infects both
      goats and sheep and is closely related to maedi-visna virus that infects sheep;
      collectively, these viruses are known as small ruminant lentiviruses (SRLV).
      Infection of goats and sheep with SRLV typically results in discrete inflammatory
      diseases which include arthritis, mastitis, pneumonia or encephalomyelitis. SRLV
      infected animals concurrently demonstrating lentivirus-associated lesions in
      tissues of lung, mammary gland, joint synovium and the central nervous system are
      either very rare or have not been reported. Here we describe a novel CAEV
      promoter isolated from a sheep with multisystemic lentivirus-associated
      inflammatory disease including interstitial pneumonia, mastitis, polyarthritis
      and leukomyelitis. A single, novel SRLV promoter was cloned and sequenced from
      five different anatomical locations (brain stem, spinal cord, lung, mammary gland
      and carpal joint synovium), all of which demonstrated lesions characteristic of
      lentivirus associated inflammation. This SRLV promoter isolate was found to be
      closely related to CAEV promoters isolated from goats in northern California and
      other parts of the world. The promoter was denoted CAEV-ovine-MS (multisystemic
      disease); the stability of the transcription factor binding sites within the U3
      promoter sequence are discussed. 

PMID- 23955502
TI  - Cleaning and asthma characteristics in women.
AB  - BACKGROUND: We aimed to assess the associations between occupational exposure to
      cleaning products, a gender-related exposure, and asthma characteristics,
      considering clinical, immunological and inflammatory aspects. METHODS: Analyses
      were conducted in 391 women (73 with adult-onset asthma) from the follow-up of
      the Epidemiological Study on the Genetics and Environment of Asthma (EGEA).
      Occupational exposure to cleaning/disinfecting products was estimated using the
      asthma-specific job-exposure-matrix (44 women exposed). RESULTS: Occupational
      exposures were associated with more symptomatic asthma (odds ratio (95% CI):
      2.8(1.2-6.4)) and severe asthma (5.1(1.7-15.3)). An association was suggested for
      poorly controlled asthma (2.2(0.9-5.5)). Associations were observed for asthma
      without positive skin prick test (3.0(1.1-8.3)), with a low IgE level (2.8(1.2
      6.2)), and with a low eosinophil count (3.2(1.5-7.1)). CONCLUSIONS: Results
      strengthen the evidence of a deleterious role of cleaning products in asthma and
      are consistent with the hypothesis of non-allergic mechanisms in relation to
      workplace cleaning exposures.

PMID- 23955503
TI  - Changes in rumen bacterial community composition in steers in response to dietary
      nitrate.
AB  - The effect of dietary nitrate supplementation on rumen bacterial community
      composition was examined in beef steers fed either a nitrate-N diet or urea-N
      diet. An automated method of ribosomal intergenic spacer analysis was applied to
      solid and liquid fractions of ruminal contents to allow comparison of bacterial
      communities. Supplemental N source affected relative population size of four
      amplicon lengths (ALs) in the liquid fraction and three ALs in the solid
      fraction. Five ALs were more prevalent after adaptation to nitrate.
      Correspondence analysis indicated that feeding the steers the nitrate-N diet
      versus urea-N diet changed the bacterial community composition in the liquid but
      not in the solid fraction. This led to an investigation of the relative sizes of
      potential nitrate-reducing populations. Mannheimia succiniciproducens,
      Veillonella parvula, and Campylobacter fetus were obtained from nitrate
      enrichment culture and quantified by real-time PCR based on 16S rRNA sequence.
      Nitrate supplementation increased the percentage of C. fetus in the liquid and
      solid phases, and in solid phase, the percentage of M. succiniciproducens
      increased. No change in species prevalence was observed for V. parvula. However,
      even after adaptation to dietary nitrate, the relative population sizes for all
      three putative nitrate-reducing species were very low (<0.06 % of 16S rRNA gene
      copy number). The liquid-associated bacterial community composition changed due
      to nitrate supplementation, and at least part of this change reflects an increase
      in the species prevalence of C. fetus, a species which is not typically regarded
      as a ruminal inhabitant. 

PMID- 23955504
TI  - LodB is required for the recombinant synthesis of the quinoprotein L-lysine
      epsilon-oxidase from Marinomonas mediterranea.
AB  - Marinomonas mediterranea is a marine gamma-proteobacterium that synthesizes LodA,
      a novel L-lysine-epsilon-oxidase (E.C. 1.4.3.20). This enzyme oxidizes L-lysine
      generating 2-aminoadipate 6-semialdehyde, ammonium, and hydrogen peroxide. Unlike
      other L-amino acid oxidases, LodA is not a flavoprotein but contains a quinone
      cofactor. LodA is encoded by an operon with two genes, lodA and lodB. In the
      native system, LodB is required for the synthesis of a functional LodA. In this
      study, we report the recombinant expression of LodA in Escherichia coli using
      vectors that allow its expression and accumulation in the cytoplasm. To reveal
      the L-lysine-epsilon-oxidase activity using the Amplex Red method for hydrogen
      peroxide detection, it is necessary to first remove the E. coli cytoplasmic
      catalases. The flavoprotein LodB is the only M. mediterranea protein required in
      the recombinant system for the generation of the cofactor of LodA. In the absence
      of LodB, LodA does not contain the quinone cofactor and remains in an inactive
      form. The results presented indicate that LodB participates in the
      posttranslational modification of LodA that generates the quinone cofactor.

PMID- 23955505
TI  - Tentative biosynthetic pathways of some microbial diketopiperazines.
AB  - Cyclodipeptides and their derivatives, the diketopiperazines (DKPs), constitute a
      large class of natural products that exhibit various biological properties. Until
      recently, there are a few characterized DKP biosynthetic pathways. In all these
      cases, the formation of the cyclodipeptides that harbor the DKP scaffold is
      catalyzed either by nonribosomal peptide synthetases or by cyclodipeptide
      synthases. This review focuses on the DKP biosynthetic pathways and their
      associated molecular mechanisms. 

PMID- 23955506
TI  - Heparin for assisted reproduction.
AB  - BACKGROUND: Heparin as an adjunct in assisted reproduction (peri-implantation
      heparin) is given at or after egg collection or at embryo transfer during
      assisted reproduction. Heparin has been advocated to improve embryo implantation
      and clinical outcomes.  It has been proposed that heparin enhances the intra
      uterine environment by improving decidualisation with an associated activation of
      growth factors and a cytokine expression profile in the endometrium that is
      favourable to pregnancy. OBJECTIVES: To investigate whether the administration of
      heparin around the time of implantation (peri-implantation heparin) improves
      clinical outcomes in subfertile women undergoing assisted reproduction. SEARCH
      METHODS: A comprehensive and exhaustive search strategy was developed in
      consultation with the Trials Search Co-ordinator of the Cochrane Menstrual
      Disorders and Subfertility Group (MDSG). The strategy was used in an attempt to
      identify all relevant studies regardless of language or publication status
      (published, unpublished, in press, and in progress). Relevant trials were
      identified from both electronic databases and other resources (last search 6 May
      2013). SELECTION CRITERIA: All randomised controlled trials (RCTs) were included
      where peri-implantation heparin was given during assisted reproduction. Peri
      implantation low molecular weight heparin (LMWH) during IVF/ICSI was given at or
      after egg collection or at embryo transfer in the included studies. Live birth
      rate was the primary outcome. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed the eligibility and quality of trials and extracted
      relevant data. The quality of the evidence was evaluated using GRADE methods.
      MAIN RESULTS: Three RCTs (involving 386 women) were included in the review.Peri
      implantation LMWH administration during assisted reproduction was associated with
      a significant improvement in live birth rate compared with placebo or no LMWH
      (odds ratio (OR) 1.77, 95% confidence interval (CI) 1.07 to 2.90, three studies,
      386 women, I(2) = 51%, very low quality evidence with high heterogeneity). There
      was also a significant improvement in the clinical pregnancy rate with use of
      LMWH (OR 1.61, 95% CI 1.03 to 2.53, three studies, 386 women, I(2) = 29%, very
      low quality evidence with low heterogeneity).However these findings should be
      interpreted with extreme caution as they were dependent upon the choice of
      statistical method: they were no longer statistically significant when a random
      effects model was used.Adverse events were poorly reported in all included
      studies, with no comparative data available. However, LMWH did cause adverse
      effects including bruising, ecchymosis, bleeding, thrombocytopenia and allergic
      reactions. It appeared that these adverse effects were increased if heparin
      therapy was used over a longer duration. AUTHORS' CONCLUSIONS: The results of
      this Cochrane review of three randomised controlled trials with a total of 386
      women suggested that peri-implantation LMWH in assisted reproduction treatment
      (ART) cycles may improve the live birth rate in women undergoing assisted
      reproduction. However, these results were dependent on small low quality studies
      with substantial heterogeneity, and were sensitive to the choice of statistical
      model. There were side effects reported with use of heparin, including bruising
      and bleeding, and no reliable data on long-term effects. The results do not
      justify this use of heparin outside well-conducted research trials.These findings
      need to be further investigated with well-designed, adequately powered, double
      blind, randomised, placebo-controlled, multicentre trials. Further investigations
      could also focus on the effects of the local (uterine) and not systemic
      application of heparin during ART.

PMID- 23955508
TI  - Health beliefs, low mood, and somatizing tendency: contribution to incidence and
      persistence of musculoskeletal pain with and without reported disability.
AB  - OBJECTIVE: This study aims to investigate whether associations of psychological
      risk factors with the incidence and persistence of disabling musculoskeletal pain
      differ from those for non-disabling musculoskeletal pain. METHODS: As part of the
      international Cultural and Psychosocial Influences in Disability (CUPID) study,
      1105 Spanish nurses and office workers were asked at baseline about health
      beliefs concerning pain, mental health, and somatizing tendency. Musculoskeletal
      pain in the past months at ten anatomical sites (back, neck, and left and right
      shoulder, elbow, wrist/hand, and knee) was ascertained at baseline and one year
      later. Pain was classed as disabling if it made >=1 specified everyday activities
      difficult or impossible. Multilevel multinomial logistic regression modeling was
      used to explore associations of baseline risk factors with pain outcomes at
      follow-up, conditioned on pain status at baseline. RESULTS: A total of 971
      participants (87.9%) completed follow-up. Among anatomical sites that were pain
      free at baseline, the development of disabling musculoskeletal pain was predicted
      by pessimistic beliefs about pain prognosis [odds ratio (OR) 1.5, 95% confidence
      interval (95% CI) 1.0-2.1], poor mental health (OR 2.0, 95% CI 1.3-3.0), and
      somatizing tendency (OR 4.0, 95% CI 2.5-6.4). Adverse beliefs about prognosis
      were also associated with the transition from non-disabling to disabling
      musculoskeletal pain (OR 3.7, 95% CI 1.1-12.5) and the persistence of disabling
      musculoskeletal pain (OR 2.5, 95% CI 1.2-5.5), which was already present at
      baseline. Associations with non-disabling musculoskeletal pain were weaker and
      less consistent. CONCLUSION: Our findings suggest that established psychological
      risk factors relate principally to the disability that arises from
      musculoskeletal pain.

PMID- 23955509
TI  - Awake craniotomy may further improve neurological outcome of intraoperative MRI
      guided brain tumor surgery.
AB  - BACKGROUND: Results of awake craniotomy are compared to results of resections
      done under general anesthesia in patients operated with IMRI control. We
      hypothesized that stimulation of the cortex and white matter during awake surgery
      supplements IMRI control allowing for safer resection of eloquent brain area
      tumors. METHODS: The study group consisted of 20 consecutive patients undergoing
      awake craniotomy with IMRI control. Resection outcome of these patients was
      compared to a control group of 20 patients operated in the same IMRI suite but
      under general anesthesia without cortical stimulation. The control group was
      composed of those patients whose age, sex, tumor location, recurrence and
      histology best matched to patients in study group. RESULTS: Cortical stimulation
      identified functional cortex in eight patients (40 %). Postoperatively the
      neurological condition in 16 patients (80 %) in the study group was unchanged or
      improved compared with 13 patients (65 %) in the control group. In both groups,
      three patients (15 %) had transient impairment symptoms. There was one patient (5
      %) with permanent neurological impairment in the study group compared to four
      patients (20 %) in the control group. These differences between groups were not
      statistically significant. There was no surgical mortality in either group and
      the overall infection rate was 5 %. Mean operation time was 4 h 45 min in the
      study group and 3 h 15 min in the control group. CONCLUSIONS: The study consisted
      of a limited patient series, but it implies that awake craniotomy with bipolar
      cortical stimulation may help to reduce the risk of postoperative impairment
      following resection of tumors located in or near speech and motor areas also
      under IMRI control.

PMID- 23955510
TI  - Suboccipital endoscopic management of the entrapped fourth ventricle: technical
      note.
AB  - BACKGROUND: Entrapped fourth ventricle is the result of both inlet aqueduct and
      outlet fourth ventricular midline and lateral foraminae obstruction. It occurs as
      a sequalae of intracranial hemorrhagic or inflammatory disease condition. Usually
      it presents after previous shunting for communicating hydrocephalus with a period
      of improvement, after which manifestations of posterior fossa expanding process
      appear. The diagnosis of this rare condition is easy considering the patient past
      history and the recent clinical state, together with the midline CSF density of
      the dilated fourth ventricle in either the CT or MR images. The treatment options
      for this condition include open and endoscopic approaches together with the
      traditional ventricular to extracranial CSF diversionary procedures. OBJECTIVE:
      The aim of the study was to adopt a procedure for treatment of entrapped fourth
      ventricle that carries the advantage of the minimally invasive technique thus
      avoiding the complications of the traditional opened and shunt surgeries as well
      as decreasing multiple procedures due to aqueduct restenosis or stent fall.
      METHODS: Thirteen patients with symptomatic entrapped fourth ventricle underwent
      suboccipital endoscopic trans-fourth ventricular aqueductoplasty from May 2007
      till November 2011. The Gabb endoscopic system was used and aqueductoplasty was
      performed using 3F Fogarty balloon followed by stent placement. Nine patients
      were females. The mean age was 3.6 years and the mean follow up period was 23
      months. All cases had a previous one or two supratentorial VP shunt placement.
      RESULTS: Short stent was used in eight patients. During the follow up, stent
      migration occurred in five of them. Three of these five patients developed
      posterior fossa compression manifestations due to aqueduct restenosis. Long stent
      from the aqueduct till the bur hole site for these three patients and the
      following five patients was used. All cases showed both clinical and radiologic
      improvement. Apart from the stent migration, no procedure-related complications
      were encountered. CONCLUSION: Endoscopic suboccipital paramedian aqueductoplasty
      with the use of a stent is a safe and effective surgical option that-in our
      opinion-should stand as the first line treatment for the entrapped fourth
      ventricle. Long stent is better used after aqueductoplasty to avoid the
      restenosis if no stent is used or stent fall after short stents. However, good
      case selection, familiarity with this fairly common endoscopic approach and
      longer follow-up is needed for obtaining an optimal result.

PMID- 23955511
TI  - On the anthropological foundation of bioethics: a critique of the work of J.-F.
      Malherbe.
AB  - In this article, I critically analyze the anthropological foundation of the
      bioethics of philosopher Jean-Francois Malherbe, particularly as presented in his
      book, Pour une Ethique de la Medecine. Malherbe argues that such practices as
      organ donation and transplants, assisted reproduction, resuscitation, and other
      uses of biotechnologies in contemporary medicine are unethical because they go
      against essential human nature. Furthermore, he uses this position as a basis to
      prescribe public policy and institutional practice. In contrast, I argue not only
      that 'human nature' is much more malleable and adaptive to changes in technology
      and society than Malherbe allows, but also that his criticisms of medicine and
      technoscientific development overstep the bounds of the social function of
      philosophical ethics, which is to inform and clarify public debate. Public policy
      and institutional practice is thus best left to the democratic political process
      under the parameters of the just rule of law. 

PMID- 23955512
TI  - Cyclosporine A at reperfusion fails to reduce infarct size in the in vivo rat
      heart.
AB  - We examined the effects on infarct size and mitochondrial function of ischemic
      (Isch), cyclosporine A (CsA) and isoflurane (Iso) preconditioning and
      postconditioning in the in vivo rat model. Anesthetized open-chest rats underwent
      30 min of ischemia followed by either 120 min (protocol 1: infarct size
      assessment) or 15 min of reperfusion (protocol 2: assessment of mitochondrial
      function). All treatments administered before the 30-min ischemia (Pre-Isch, Pre
      CsA, Pre-Iso) significantly reduced infarct as compared to control. In contrast,
      only Post-Iso significantly reduced infarct size, while Post-Isch and Post-CsA
      had no significant protective effect. As for the postconditioning-like
      interventions, the mitochondrial calcium retention capacity significantly
      increased only in the Post-Iso group (+58 % vs control) after succinate
      activation. Only Post-Iso increased state 3 (+177 and +62 %, for G/M and
      succinate, respectively) when compared to control. Also, Post-Iso reduced the
      hydrogen peroxide (H2O2) production (-46 % vs control) after complex I
      activation. This study suggests that isoflurane, but not cyclosporine A, can
      prevent lethal reperfusion injury in this in vivo rat model. This might be
      related to the need for a combined effect on cyclophilin D and complex I during
      the first minutes of reperfusion. 

PMID- 23955513
TI  - Induction of the endoplasmic reticulum stress and autophagy in human lung
      carcinoma A549 cells by anacardic acid.
AB  - Anacardic acid (AA, 2-hydroxy-6-pentadecylbenzoic acid), a constituent of the
      cashew-nut shell, has a variety of beneficial effects on the treatment of cancer
      and tumors. However, the fact that AA induces ER stress and autophagy in cancer
      cell is not known. We investigated the effect of AA on ER-stress and autophagy
      induced cell death in cancer cells. Because of our interest in lung cancer, we
      used the non-small cell lung adenocarcinoma A549 cells treated with 3.0 MUg/ml of
      AA for this research. In this research we found that AA induces intracellular
      Ca(2+) mobilization and ER stress. AA induced the ER stress-inducing factors,
      especially IRE1alpha, and the hallmarks of UPR, Grp78/Bip and GADD153/CHOP. AA
      inhibited the expression of p-PERK and its downstream substrate, p-elF2alpha. We
      also demonstrated that AA induces autophagy. Up-regulation of autophagy-related
      genes and the appearance of autophagosome in transfected cells with green
      fluorescent protein (GFP)-LC3 and GFP-Beclin1 plasmids showed the induction of
      autophagy in AA-treated A549 cells. The morphological analysis of intracellular
      organelles by TEM also showed the evidence that AA induces ER stress and
      autophagy. For the first time, our research showed that AA induces ER stress and
      autophagy in cancer cells.

PMID- 23955514
TI  - Capsaicin modulates proliferation, migration, and activation of hepatic stellate
      cells.
AB  - Capsaicin, the active component of chili pepper, has been reported to have
      antiproliferative and anti-inflammatory effects on a variety of cell lines. In
      the current study, we aimed to investigate the effects of capsaicin during HSC
      activation and maintenance. Activated and freshly isolated HSCs were treated with
      capsaicin. Proliferation was measured by incorporation of EdU. Cell cycle arrest
      and apoptosis were investigated using flow cytometry. The migratory response to
      chemotactic stimuli was evaluated by a modified Boyden chamber assay. Activation
      markers and inflammatory cytokines were determined by qPCR, immunocytochemistry,
      and flow cytometry. Our results show that capsaicin reduces HSC proliferation,
      migration, and expression of profibrogenic markers of activated and primary mouse
      HSCs. In conclusion, the present study shows that capsaicin modulates
      proliferation, migration, and activation of HSC in vitro. 

PMID- 23955515
TI  - Computational study of molecular properties with dual basis sets.
AB  - We have studied the performance of dual basis (DB) sets for the evaluation of
      molecular properties via second order Moller-Plesset perturbation theory (MP2).
      In addition to savings derived from using a trimmed basis set for the underlying
      Hartree-Fock (HF) calculation, we pursued a systematic truncation of the virtual
      subspace for further reductions in computational overhead during the post-HF
      step. Calculated total energies and molecular properties within the DB framework
      without virtual space truncation are generally in excellent agreement with full
      basis calculations. When aug-cc-pV5Z is used as the parent basis, mean absolute
      error for DB-HF (DB-MP2) total energies of molecules within our test set is 9.7 *
      10(-5) au (8.0 * 10(-5) au) while mean absolute relative errors for static
      electrical response properties like dipole moments, isotropic dipole
      polarizabilities and polarizability anisotropies are 0.15% (0.14%), 0.56%
      (0.72%), and 0.76% (0.83%) respectively. When DB is coupled with virtual space
      truncation at the MP2 level, the corresponding errors are larger but still within
      2% of full basis values.

PMID- 23955516
TI  - A comparison of nasal trauma in preterm infants extubated to either heated
      humidified high-flow nasal cannulae or nasal continuous positive airway pressure.
AB  - The objectives of this study were (1) to devise a nasal trauma score for preterm
      infants receiving non-invasive respiratory support, (2) to compare the incidence
      of nasal trauma in preterm infants <32 weeks gestation randomised to either nasal
      continuous positive airway pressure (NCPAP) or heated humidified high-Flow nasal
      cannulae (HHHFNC), in the first 7 days post-extubation and (3) to assess the
      effect of two different nasal dressings in those assigned to NCPAP. We randomly
      assigned preterm ventilated infants to receive Vapotherm(r) HHHFNC or NCPAP post
      extubation. Infants receiving HHHFNC were treated with Sticky Whiskers(r) and
      infants receiving NCPAP received either Sticky Whiskers(r) or Cannualaide(r)
      nasal dressings. Bedside nursing staff scored six sites on each infant's nose for
      erythema, bleeding or ulceration. Scores were recorded three times daily for the
      first 7 days post-extubation. The sum of these 21 scores was used as the summary
      measure of nasal trauma. The mean nasal trauma score for infants assigned HHHFNC
      was 2.8 (SD 5.7) compared to 11.7 for NCPAP (SD 10.4), p < 0.001. There was no
      difference in mean trauma score between infants on NCPAP assigned Sticky
      Whiskers(r) 14.4 (SD 12.5) or Cannualaide(r) 9.5 (SD 7.3), p = 0.06. CONCLUSION:
      HHHFNC resulted in significantly less nasal trauma in the first 7 days post
      extubation than NCPAP and was most significant in infants <28 weeks of gestation.
      The use of protective dressings was not associated with decreased nasal trauma
      for infants on NCPAP.

PMID- 23955517
TI  - Inferring the geographic mode of speciation by contrasting autosomal and sex
      linked genetic diversity.
AB  - When geographic isolation drives speciation, concurrent termination of gene flow
      among genomic regions will occur immediately after the formation of the barrier
      between diverging populations. Alternatively, if speciation is driven by
      ecologically divergent selection, gene flow of selectively neutral genomic
      regions may go on between diverging populations until the completion of
      reproductive isolation. It may also lead to an unsynchronized termination of gene
      flow between genomic regions with different roles in the speciation process.
      Here, we developed a novel Approximate Bayesian Computation pipeline to infer the
      geographic mode of speciation by testing for a lack of postdivergence gene flow
      and a concurrent termination of gene flow in autosomal and sex-linked markers
      jointly. We applied this approach to infer the geographic mode of speciation for
      two allopatric highland rosefinches, the vinaceous rosefinch Carpodacus vinaceus
      and the Taiwan rosefinch C. formosanus from DNA polymorphisms of both autosomal
      and Z-linked loci. Our results suggest that the two rosefinch species diverged
      allopatrically approximately 0.5 Ma. Our approach allowed us further to infer
      that female effective population sizes are about five times larger than those of
      males, an estimate potentially useful when comparing the intensity of sexual
      selection across species. 

PMID- 23955518
TI  - MitoFish and MitoAnnotator: a mitochondrial genome database of fish with an
      accurate and automatic annotation pipeline.
AB  - Mitofish is a database of fish mitochondrial genomes (mitogenomes) that includes
      powerful and precise de novo annotations for mitogenome sequences. Fish occupy an
      important position in the evolution of vertebrates and the ecology of the
      hydrosphere, and mitogenomic sequence data have served as a rich source of
      information for resolving fish phylogenies and identifying new fish species. The
      importance of a mitogenomic database continues to grow at a rapid pace as massive
      amounts of mitogenomic data are generated with the advent of new sequencing
      technologies. A severe bottleneck seems likely to occur with regard to mitogenome
      annotation because of the overwhelming pace of data accumulation and the
      intrinsic difficulties in annotating sequences with degenerating transfer RNA
      structures, divergent start/stop codons of the coding elements, and the
      overlapping of adjacent elements. To ease this data backlog, we developed an
      annotation pipeline named MitoAnnotator. MitoAnnotator automatically annotates a
      fish mitogenome with a high degree of accuracy in approximately 5 min; thus, it
      is readily applicable to data sets of dozens of sequences. MitoFish also contains
      re-annotations of previously sequenced fish mitogenomes, enabling researchers to
      refer to them when they find annotations that are likely to be erroneous or while
      conducting comparative mitogenomic analyses. For users who need more information
      on the taxonomy, habitats, phenotypes, or life cycles of fish, MitoFish provides
      links to related databases. MitoFish and MitoAnnotator are freely available at
      http://mitofish.aori.u-tokyo.ac.jp/ (last accessed August 28, 2013); all of the
      data can be batch downloaded, and the annotation pipeline can be used via a web
      interface. 

PMID- 23955519
TI  - Effects of medical treatment on the prognosis and risk of embolic events in
      patients with severe aortic plaque.
AB  - AIM: The optimal treatment strategy for patients with aortic atheroma is not well
      established because data regarding medical treatment for such patients are
      lacking, especially with respect to the Japanese population. The purpose of this
      study was to clarify the effects of medical treatment on the risk of embolic
      events and mortality in patients with severe aortic plaque. METHODS: We
      retrospectively investigated 75 consecutive patients with severe aortic plaque
      detected on transesophageal echocardiography (TEE) between 1995 and 2005. The
      occurrence of embolic events and all-cause death in the period after TEE was
      assessed. The cumulative incidence of subsequent embolic events and death was
      evaluated in relation to specific medical treatments, including statins,
      antiplatelet drugs and warfarin. RESULTS: Embolic events occurred in 27 patients
      (36%) and death occurred in 37 patients (49%) during follow-up (5.6+/-3.0 years).
      The patients who experienced embolic events had a significantly higher prevalence
      of previous embolic events, atrial fibrillation and hemodialysis than the
      patients who did not experience embolic events. Univariate and multivariate
      analyses showed that the use of statins and/or antiplatelet drugs was
      significantly associated with a low incidence of death but not with a low
      incidence of embolic events. On the other hand, warfarin exhibited neither
      beneficial nor harmful effects on the incidence of embolic events or death.
      CONCLUSIONS: Statin and antiplatelet drugs have beneficial effects on the
      prognosis of patients with severe aortic plaque diagnosed on TEE.

PMID- 23955520
TI  - Immunochemical characterization of synthetic hexa-, octa- and decasaccharide
      conjugate vaccines for Vibrio cholerae O:1 serotype Ogawa with emphasis on
      antigenic density and chain length.
AB  - Cholera remains to be a global health problem without suitable vaccines for
      endemic control or outbreak relief. Here we describe a new parenteral vaccine
      based on neoglyco-conjugate of synthetic fragments of O-specific polysaccharide
      (O-SP) of Vibrio cholerae O1, serotype Ogawa. Hexa-, octa- and decasaccharides of
      the O-SP with carboxylic acid at the reducing end were chemically synthesized and
      conjugated to tetanus toxoid (TT). The conjugates prepared by a novel linking
      scheme consisted of 17-atom linker of hydrazide and alkyl bonds elicited robust
      serum IgG anti-LPS responses with vibriocidal activities in mice. There is a
      length dependence in immune response with decasaccharide conjugates elicited the
      highest anti-LPS IgG. There seems to be an indication that regardless of the
      carbohydrate chain length, a molar ratio of 230 +/- 10 monosaccharide units per
      TT induced high antibody response. The conjugates also elicited cross-reactive
      antibodies to serotype Inaba. The formulation of the proposed cholera conjugate
      vaccine, similar to other licensed polysaccharide vaccine, is suitable for
      children immunization. A parenteral cholera vaccine could overcome the
      diminishing immunogenicity in most of oral vaccines due to the gastrointestinal
      complexity and environmental enteropathy in children living in impoverished
      environment and could be considered for global cholera immunization.

PMID- 23955522
TI  - Anthropometric evaluation and micronutrients intake in patients submitted to
      laparoscopic Roux-en-Y gastric bypass with a postoperative period of >= 1 year.
AB  - BACKGROUND: Bariatric surgery is indicated as the most effective treatment for
      morbid obesity; the Roux-en-Y gastric bypass (RYGB) is considered the procedure
      of choice. However, nutritional deficiency may occur in the postoperative period
      as a result of reduced gastric capacity and change in nutrients absorption in the
      gastrointestinal tract. The prescription of vitamin and mineral supplementation
      is a common practice after RYGB; however, it may not be sufficient to prevent
      micronutrient deficiencies. The aim of this study was to quantify the
      micronutrient intake in patients undergoing RYGB and verify if the intake of
      supplementation would be enough to prevent nutritional deficiencies. METHODS: The
      study was conducted on 60 patients submitted to RYGB. Anthropometric, analytical,
      and nutritional intake data were assessed preoperatively and 1 and 2 years
      postoperatively. The dietary intake was assessed using 24-h food recall; the
      values of micronutrients evaluated (vitamin B12, folic acid, iron, and calcium)
      were compared to the dietary reference intakes (DRI). RESULTS: There were
      significant differences (p < 0.05) between excess weight loss at the first and
      second year (69.9 +/- 15.3 vs 9.6 +/- 62.9 %). In the first and second year after
      surgery, 93.3 and 94.1 % of the patients, respectively, took the supplements as
      prescribed. Micronutrient deficiencies were detected in the three evaluation
      periods. At the first year, there was a significant reduction (p < 0.05) of B12,
      folic acid, and iron intake. CONCLUSIONS: Despite taking vitamin and mineral
      supplementation, micronutrient deficiencies are common after RYGB. In the second
      year after surgery, micronutrient intake remains below the DRI.

PMID- 23955521
TI  - Gastric bypass and sleeve gastrectomy for type 2 diabetes: a systematic review
      and meta-analysis of outcomes.
AB  - Bariatric surgery is effective in the management of type 2 diabetes (T2D) and
      obesity; however, it is not clear whether Roux-en-Y gastric bypass (GBP) or
      sleeve gastrectomy (SG) is the most effective procedure. This review compared T2D
      remission and weight loss in patients with T2D after GBP or SG. All human SG or
      GBP studies published in English between 1 Jan 2007 and 30 April 2012 reporting
      on BMI and T2D outcomes were included. Analyses were performed separately for the
      most frequent distinct time points reported after surgery. A total of 21
      prospective (three randomised control trials) and 12 retrospective studies,
      involving 1375 patients met eligibility criteria. T2D remission defined by
      hemoglobin A1c of <6.5 % for GBP and SG respectively was 67 and 56 % at 3 months,
      76 and 68 % at 12 months, and 81 and 80 % at 36 months. Greater percent excess
      BMI loss occurred at 12 months (72.5 % after GBP and 66.7 % after SG) compared
      with 3 months (45.9 % after GBP and 25.9 % after SG). There was no significant
      difference in either T2D remission or weight loss with GBP compared with SG. Both
      GBP and SG result in similar early remission of T2D in 67 and 56 % of patients at
      3 months respectively with modest additional T2D remission with time, although
      weight loss with both procedures increase substantially between 3 and 12 months
      post-operatively. Further randomised controlled trials comparing SG and GBP in
      patients with T2D using comparable definitions of diabetes remission with long
      term follow-up are needed to evaluate relative benefits.

PMID- 23955523
TI  - [Technical orthopedics. Importance in an increasingly operatively oriented
      faculty].
AB  - The foundation of the German Society for Orthopedics in 1901 was due to a
      separation from the faculty of surgery because a surgical approach alone did not
      adequately deal with the symptoms. Orthopedists were initially considered as a
      fringe group. The conservative treatment approach was initially at the forefront
      and operative measures were a side line. The main aim was the rehabilitation of
      patients into a normal life as best as possible. In the conservative area
      treatment with orthopedic technical aids and appliances rapidly came to play an
      important role and a great multitude of technical appliances were developed with
      sometimes very different possible applications. Despite the clearly improved
      operative treatment approaches in orthopedics and trauma surgery, technical
      orthopedics still plays a substantial role even today. Healing and supportive
      aids and appliances are of decisive importance for the treatment of a multitude
      of diseases and handicaps. They stabilize and improve operative treatment results
      and often result in new approaches. This depends on cooperation between
      technicians, therapists and physicians in a team, even in the scientific field.
      Evidence-based studies on the effectiveness of technical aids are currently still
      uncommon but recently some clear evidence for effectiveness could be shown.
      Scientifically this is a very varied field of work. The demographic development
      presents new requirements which must be dealt with. Technical solutions are often
      very promising especially in this field. Technical orthopedics remains an
      important component of the specialty of orthopedics and trauma surgery and with
      an increasing tendency due to more recent research and development.

PMID- 23955524
TI  - Specific detection and imaging of enzyme activity by signal-amplifiable self
      assembling (19)F MRI probes.
AB  - Specific turn-on detection of enzyme activities is of fundamental importance in
      drug discovery research, as well as medical diagnostics. Although magnetic
      resonance imaging (MRI) is one of the most powerful techniques for noninvasive
      visualization of enzyme activity, both in vivo and ex vivo, promising strategies
      for imaging specific enzymes with high contrast have been very limited to date.
      We report herein a novel signal-amplifiable self-assembling (19) F NMR/MRI probe
      for turn-on detection and imaging of specific enzymatic activity. In NMR
      spectroscopy, these designed probes are "silent" when aggregated, but exhibit a
      disassembly driven turn-on signal change upon cleavage of the substrate part by
      the catalytic enzyme. Using these (19) F probes, nanomolar levels of two
      different target enzymes, nitroreductase (NTR) and matrix metalloproteinase
      (MMP), could be detected and visualized by (19) F NMR spectroscopy and MRI.
      Furthermore, we have succeeded in imaging the activity of endogenously secreted
      MMP in cultured media of tumor cells by (19) F MRI, depending on the cell lines
      and the cellular conditions. These results clearly demonstrate that our turn-on
      (19) F probes may serve as a screening platform for the activity of MMPs. 

PMID- 23955525
TI  - Plasma cortisol in Alzheimer's disease with or without depressive symptoms.
AB  - BACKGROUND: Cortisol is presumed to be a risk factor for stress- and age-related
      disorders, such as depressive disorder and Alzheimer's disease (AD). The aim of
      this study was to investigate the association of plasma cortisol concentration
      with AD in presence or absence of comorbid depressive symptoms. MATERIAL AND
      METHODS: Plasma cortisol concentration was measured in 80 AD patients (35 of them
      with depressive symptoms), 27 elderly depressive patients without AD, and 37
      elderly controls. RESULTS: Compared to controls, a significant increase of mean
      plasma cortisol was found in AD patients but not in depressive patients. Plasma
      cortisol was positively correlated with cognitive impairment in AD patients. We
      confirmed a U-shaped association between plasma cortisol and major depression and
      a linear association between plasma cortisol and AD without depressive symptoms.
      Significantly increased relative risk of disease in people with high plasma
      cortisol was found for AD with depressive symptoms and for AD with mild dementia.
      CONCLUSIONS: Plasma cortisol reflects the degree of cognitive impairment in AD
      rather than the severity of comorbid depression. We confirmed that both
      hypercortisolemia and hypocortisolemia are associated with depressive disorder.
      Significant association between high plasma cortisol and AD was found, supporting
      the use of high plasma cortisol as a component of a panel of biochemical markers
      for AD with depressive symptoms as well as AD in the early stage of dementia
      development.

PMID- 23955526
TI  - Preserved white matter integrity is a marker of familial longevity.
AB  - OBJECTIVE: Brain tissue integrity is highly heritable, and its decline is a
      common phenomenon of ageing. This study aimed to determine whether the phenotype
      of familial longevity is marked by a relative preservation of brain tissue
      microstructure. METHODS: Participants were enrolled in the Leiden Longevity
      Study. In total, 185 middle-aged to elderly offspring of nonagenarian siblings,
      who were enriched for familial factors of longevity, were contrasted with 171
      environment- and age-matched controls. All subjects underwent 3T whole brain
      magnetic resonance diffusion tensor imaging. RESULTS: Voxel-wise analysis
      revealed widespread age-related decrease of white matter fractional anisotropy
      and increases of axial, radial, and mean diffusivity (all p < 0.003). Offspring
      showed higher mean white matter fractional anisotropy (mean [standard error]:
      offspring, 0.3232 [0.0009]; controls, 0.3212 [0.0009]; p = 0.04) compared to
      control subjects independent of cardiovascular risk factors. When differences in
      white matter diffusion parameters between offspring and control subjects were
      assessed voxel-wise, offspring showed higher white matter fractional anisotropy
      and lower white matter radial diffusivity predominantly in the callosal genu and
      body (both p < 0.003). With the effect of chronological age on white matter
      microstructure taken into account, offspring can be considered 4.5 years
      "biologically younger" compared to control subjects with regard to white matter
      integrity. INTERPRETATION: Both middle-aged to elderly offspring of nonagenarian
      siblings and control subjects show common age-related decline of white matter
      integrity, but it is less marked in the callosal genu and body in the offspring.
      This corresponds to a biological age benefit of 4.5 years of the offspring as
      compared to the control subjects.

PMID- 23955528
TI  - Evaluation of disease extent with the Crohn's disease endoscopic index of
      severity.

PMID- 23955527
TI  - Use of CT colonography in the English Bowel Cancer Screening Programme.
AB  - OBJECTIVE: To examine use of CT colonography (CTC) in the English Bowel Cancer
      Screening Programme (BCSP) and investigate detection rates. DESIGN: Retrospective
      analysis of routinely coded BCSP data. Guaiac faecal occult blood test (gFOBt)
      positive screenees undergoing CTC from June 2006 to July 2012 as their first-line
      colonic investigation were included. Abnormalities found at CTC, subsequent
      polyp, adenoma and cancer detection and positive predictive value (PPV) were
      calculated. Detection rates were compared with those observed in gFOBt-positive
      screenees investigated by colonoscopy. Multilevel logistic regression was used to
      examine factors associated with variable detection. RESULTS: 2731 screenees
      underwent CTC. Colorectal cancer (CRC) or polyps were suspected in 1027
      individuals (37.6%; 95% CI 33.8% to 41.4%); 911 of these underwent confirmatory
      testing. 124 screenees had CRC (4.5%) and 533 had polyps (19.5%), 468 adenomatous
      (17.1%). Overall detection was 24.1% (95% CI 21.5% to 26.6%) for CRC or polyps
      and 21.7% (95% CI 19.2% to 24.1%) for CRC or adenoma. Advanced neoplasia was
      detected in 504 screenees (18.5%; 95% CI 16.1% to 20.8%). PPV for CRC or polyp
      was 72.1% (95% CI 66.6% to 77.6%). By comparison, 9.0% of 72 817 screenees
      undergoing colonoscopy had cancer and 50.6% had polyps; advanced neoplasia was
      detected in 32.7%. CTC detection rates and PPV were higher at centres with
      experienced radiologists (>1000 examinations) and at high-volume centres (>175
      cases/radiologist/annum). Centres using three-dimensional interpretation detected
      more neoplasia. CONCLUSIONS: In the BCSP, detection rates after positive gFOBt
      are lower for CTC than colonoscopy, although populations undergoing the two tests
      are different. Centres with more experienced radiologists have higher detection
      and accuracy. Rigorous quality assurance of BCSP radiology is needed.

PMID- 23955529
TI  - The virulence factors of Bordetella pertussis: talented modulators of host immune
      response.
AB  - Approximately 40 million whooping cough cases and between 200,000 and 400,000
      pertussis-linked deaths are recorded each year. Although several types of
      vaccines are licensed and widely used, Bordetella pertussis continues to
      circulate in populations with high vaccine coverage of infants and children due
      to the waning of protection induced by the vaccination. B. pertussis typically
      expresses a wide array of virulence factors which promote bacterial adhesion and
      invasion by altering the local environment, including pertussis toxin, tracheal
      cytotoxin, adenylate cyclase toxin, filamentous hemagglutinin, and the
      lipooligosaccharide. The virulence factors of B. pertussis also possess
      immunomodulatory properties, exerted through their enzymatic and receptor-binding
      activities. Both pro- and anti-inflammatory effects are mediated, that can
      subvert host innate and adaptive immunity and favor the onset of a long-term
      infection. This review describes the capacities of B. pertussis virulence factors
      to modulate host immune responses and the mechanisms employed, which have been
      the subject of extensive research in the recent years, both in murine and human
      experimental systems. Knowledge of these mechanisms is gaining increasing
      importance, since it could provide in the near future the basis for the
      identification of therapeutic agents for modulating the immune system as well as
      novel molecular targets to treat pertussis. 

PMID- 23955530
TI  - Type 1 diabetes: prospective cohort studies for identification of the
      environmental trigger.
AB  - Type 1 diabetes (T1D) is one of the most common chronic diseases with childhood
      onset, and the disease incidence has increased two to fivefold over the past half
      century by as yet unknown means. T1D occurs when the body's immune system turns
      against itself, destroying in a very specific and targeted way-the pancreatic
      beta-cells. T1D results from poorly defined interactions between susceptibility
      genes and environmental determinants. In contrast to the rapid progress in
      finding T1D genes, identification and confirmation of environmental determinants
      remain a formidable challenge. This review article will give an overview of
      ongoing prospective cohort studies aiming to identify the environmental
      trigger(s) causing T1D. 

PMID- 23955531
TI  - Functional attributes of responding T cells in HCV infection: the recent advances
      in engineering functional antiviral T cells.
AB  - Hepatitis C virus (HCV) is one of the major causes of hepatocellular carcinoma
      (HCC) around the world. HCV promotes characteristics of cancer stem cells and the
      infected cells are insensitive to apoptotic signals, which lead to persistent
      antigen stimulation and T cell exhaustion in the host. In spite of new effective
      antiviral drugs, new challenges are around the corner as drug-resistant viral
      strains and drug-drug interactions have already been reported. Considering that
      there are few effective treatments available for HCC, novel immunotherapies to
      prevent HCC and late stage HCV-related liver diseases should be considered. Given
      that adoptive immunotherapy with antigen-specific T lymphocytes has emerged as an
      effective therapeutic strategy for combating cancer, there is, therefore, reason
      to examine the possibility of using highly functional HCV-reactive T cells in
      immunotherapy. This review aims to provide the current understanding of natural
      HCV responding T cells in HCV infection and to give an update on the novel
      approaches that have the capacity to ex vivo generate functional T cells for
      potential adoptive cell therapy. Approaches based on the pMHC tetramer-associated
      magnetic enrichment, exogenous HCV T cell receptor transfer, and induced
      pluripotent stem cell technologies are described herein. Their potentials as
      immunotherapeutic against HCV-related diseases are discussed. 

PMID- 23955532
TI  - Co-infections with cytomegalovirus and human herpesvirus type 7 in adult Polish
      allogeneic haematopoietic stem cell transplant recipients.
AB  - Human herpesvirus 7 (HHV-7) is widespread around the world and may also be a
      possible cofactor for cytomegalovirus (CMV) infection in haematopoietic stem cell
      transplant (HSCT) recipients. In case of viral diseases where specific treatment
      is available, real-time PCR assays constitute reliable diagnostic tools enabling
      timely initiation of appropriate therapy and rapid assessment of the efficacy of
      antiviral treatment strategies. The presence of CMV and HHV-7 was confirmed by
      the detection of viral DNA isolated from 1,027 plasma samples. A group of 69
      allogeneic HSCT (alloHSCT) recipients was examined in early post-transplant
      period using quantitative real-time PCR methods. Within the study period, 62 % of
      patients had at least once CMV DNA-emia, while HHV-7 DNA was found in 43 % of
      subjects. Co-infection between these beta-herpesviruses was detected in the
      plasma samples collected from 18 patients (26 %). Patients with concomitant HHV-7
      DNA-emia had significantly higher number of CMV DNA copies compared with those
      without HHV-7 infection (1986 vs. 432 copies/ml, p < 0.001) but there was no
      difference in duration of CMV DNA-emia between these groups. On the other hand,
      while the load of HHV-7 DNA was comparable between patients with CMV DNA-emia and
      without CMV DNA-emia, the duration of HHV-7 DNA-emia was significantly longer in
      the first group (38.5 vs. 14 days, p < 0.001). HHV-7 DNA-emia is very frequently
      detected in Polish alloHSCT recipients. In those, who have subsequent CMV
      reactivation, the coexistence of the viruses may negatively affect the kinetics
      of infection with either of them. Therefore the investigation of concomitant HHV
      7 DNA-emia could affect the prognosis of post-transplant patients suffering from
      CMV reactivation. 

PMID- 23955533
TI  - A compendium of cyclic sugar amino acids and their carbocyclic and heterocyclic
      nitrogen analogues.
AB  - This compendium focuses on functionalised sugar amino acids (SAAs) and their 3-
      to 6-membered nitrogen heterocyclic and carbocyclic analogues. The main benefit
      of using SAAs and their related nitrogen and carbon congeners in the production
      of peptidomimetics and glycomimetics is that their properties can be readily
      altered via modification of their ring size, chemical manipulation of their
      numerous functional groups and fine-tuning of the stereochemical arrangement of
      their ring substituents. These building blocks provide access to hydrophilic and
      hydrophobic peptide isosteres whose physical properties allow entry to a region
      of chemotherapeutic space which is still under-explored by medicinal chemists.
      These building blocks are also important in providing amino acids whose inherent
      conformational bias leads to predisposition to secondary structure upon
      oligomerisation in relatively short sequences. These foldamers, particularly
      those containing omega-amino acids, provide an additional opportunity to expand
      access to the control of structures by artificial peptides. The synthesis and
      biological evaluation of these building blocks in glycomimetics and
      peptidomimetics systems keep expanding the reach of the glycosciences to the
      medical sciences, provide a greater outlook onto the wide range of cellular
      functions of saccharides and their derivatives involved and greater insight into
      the nature of oligosaccharide and protein folding. 

PMID- 23955534
TI  - Patterned prevascularised tissue constructs by assembly of polyelectrolyte
      hydrogel fibres.
AB  - The in vivo efficacy of engineered tissue constructs depends largely on their
      integration with the host vasculature. Prevascularisation has been noted to
      facilitate integration of the constructs via anastomosis of preformed
      microvascular networks. Here we report a technique to fabricate aligned,
      spatially defined prevascularised tissue constructs with endothelial vessels by
      assembling individually tailored cell-laden polyelectrolyte hydrogel fibres.
      Stable, aligned endothelial vessels form in vitro within these constructs in 24
      h, and these vessels anastomose with the host circulation in a mouse subcutaneous
      model. We create vascularised adipose and hepatic tissues by co-patterning the
      respective cell types with the preformed endothelial vessels. Our study indicates
      that the formation of aligned endothelial vessels in a hydrogel is an efficient
      prevascularisation approach in the engineering of tissue constructs. 

PMID- 23955535
TI  - Dressings and topical agents for preventing pressure ulcers.
AB  - BACKGROUND: Pressure ulcers, which are localised injury to the skin, or
      underlying tissue or both, occur when people are unable to reposition themselves
      to relieve pressure on bony prominences. Pressure ulcers are often difficult to
      heal, painful and impact negatively on the individual's quality of life. The cost
      implications of pressure ulcer treatment are considerable, compounding the
      challenges in providing cost effective, efficient health services. Efforts to
      prevent the development of pressure ulcers have focused on nutritional support,
      pressure redistributing devices, turning regimes and the application of various
      topical agents and dressings designed to maintain healthy skin, relieve pressure
      and prevent shearing forces. Although products aimed at preventing pressure
      ulcers are widely used, it remains unclear which, if any, of these approaches are
      effective in preventing the development of pressure ulcers. OBJECTIVES: To
      evaluate the effects of dressings and topical agents on the prevention of
      pressure ulcers, in people of any age without existing pressure ulcers, but
      considered to be at risk of developing a pressure ulcer, in any healthcare
      setting. SEARCH METHODS: In February 2013 we searched the following electronic
      databases to identify reports of relevant randomised clinical trials (RCTs): the
      Cochrane Wounds Group Specialised Register; the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library); Database of Abstracts of
      Reviews of Effects (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process
      & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. SELECTION
      CRITERIA: We included RCTs evaluating the use of dressings, topical agents, or
      topical agents with dressings, compared with a different dressing, topical agent,
      or combined topical agent and dressing, or no intervention or standard care, with
      the aim of preventing the development of a pressure ulcer. DATA COLLECTION AND
      ANALYSIS: We assessed trials for their appropriateness for inclusion and for
      their risk of bias. This was done by two review authors working independently,
      using pre-determined inclusion and quality criteria. MAIN RESULTS: Five trials
      (940 participants) of unclear or high risk of bias compared a topical agent with
      a placebo. Four of these trials randomised by individual and one by cluster. When
      results from the five trials were combined, the risk ratio (RR) was 0.78 (95% CI
      0.47 to 1.31; P value 0.35) indicating no overall beneficial effect of the
      topical agents. When the cluster randomised trial was omitted from the analysis,
      use of topical agents reduced the pressure ulcer incidence by 36%; RR 0.64 (95%
      CI 0.49 to 0.83; P value 0.0008).Four trials (561 participants), all of which
      were of high or unclear risk of bias, showed that dressings applied over bony
      prominences reduced pressure ulcer incidence; RR 0.21 (95% CI 0.09 to 0.51; P
      value 0.0006). AUTHORS' CONCLUSIONS: There is insufficient evidence from RCTs to
      support or refute the use of topical agents applied over bony prominences to
      prevent pressure ulcers. Although the incidence of pressure ulcers was reduced
      when dressings were used to protect the skin, results were compromised by the low
      quality of the included trials. These trials contained substantial risk of bias
      and clinical heterogeneity (variations in populations and interventions);
      consequently, results should be interpreted as inconclusive. Further well
      designed trials addressing important clinical, quality of life and economic
      outcomes are justified, based on the incidence of the problem and the high costs
      associated with pressure ulcer management.

PMID- 23955536
TI  - Luffa cylindrica and phytosterols bioconversion: from shake flask to jar
      bioreactor.
AB  - Bioconversion of lipophilic compounds poorly soluble in water, such as sterols,
      required the use of chemicals and solubilizing agents. On the other hand, it was
      shown that immobilization of Mycobacterium species on the dried fruit of Luffa
      cylindrica (DFLC) allows a close interaction between immobilized cells and
      cholesterol particles and increases by then the product's yield. In this work,
      the use of DFLC in a 5-l jar bioreactor with phytosterols mixture (1 g/l) as
      substrate was assessed without addition of any chemicals or solubilizing agents.
      DFLC increased by a factor of four the volumetric productivity of androstenones
      (0.08 g/l day). Products were accumulated in the aqueous medium while substrates
      remained on the fibers of DFLC. This observation lets envisage a green semi
      continuous process of androstenone production. DFLC has no influence on cell
      growth, and is moreover natural, inexpensive, non-toxic, and mechanically strong.

PMID- 23955537
TI  - Entropies of defect formation in ceria from first principles.
AB  - We calculate entropies of formation for fully charged point defects, including
      the small polaron Ce'(Ce), in undoped fluorite-structured ceria by means of
      density functional theory in the GGA + U approximation. We discuss the behaviour
      of the entropy for the constant volume and the constant pressure case. Our
      results for constant pressure (p = 0) suggest that the change in volume, due to
      the formation of defects, dominates the entropy of formation. From the individual
      entropies of formation the entropies of Frenkel, anti-Frenkel and Schottky
      disorder as well as the entropy of reduction of ceria are obtained. At
      temperatures of about 1000 K the entropic contributions to the Gibbs energy are
      up to 0.9 eV per defect and thus are no longer negligible. For our calculated
      entropy of reduction of about 17 kB we find a remarkable agreement with
      experimental data from the literature.

PMID- 23955538
TI  - Pediatric allergic rhinitis and asthma: can the march be halted?
AB  - The strong epidemiologic and pathophysiologic link between allergic rhinitis (AR)
      and asthma has led to the concept of 'united airways disease' or 'respiratory
      allergy', implying that allergy, in its widest sense, underlies this clinical
      syndrome. Progression from AR to asthma is frequent and part of the 'atopic
      march'. Since pediatric immune responses are more adaptable and therefore may be
      more amenable to treatment, interventions at early childhood are characterized by
      a higher chance to affect the natural history of respiratory allergy. Although
      current treatments are quite effective in alleviating respiratory allergy
      symptoms, it has proven much more difficult to confirm any influence on the
      progression of the disease. Much more promising is the field of specific allergen
      immunotherapy, where current evidence, although not yet of ideal robustness,
      points towards a disease-modifying effect. In addition, newer or emerging,
      possibly more effective or more targeted interventions are promising in the
      preventive sense. 

PMID- 23955540
TI  - Cancer stemness in Wnt-driven mammary tumorigenesis.
AB  - Wnt signaling plays a central role in mammary stem cell (MaSC) homeostasis and in
      breast cancer. In particular, epigenetic alterations at different members of the
      Wnt pathway have been identified among triple-negative, basal-like breast
      cancers. Previously, we developed a mouse model for metaplastic breast
      adenocarcinoma, a subtype of triple-negative breast cancer, by targeting a
      hypomorphic mutations in the endogenous Apc gene (Apc (1572T/+)). Here, by
      employing the CD24 and CD29 cell surface antigens, we have identified a
      subpopulation of mammary cancer stem cells (MaCSCs) from Apc (1572T/+) capable of
      self-renewal and differentiation both in vivo and in vitro. Moreover,
      immunohistochemical analysis of micro- and macrolung metastases and preliminary
      intravenous transplantation assays suggest that the MaCSCs underlie metastasis at
      distant organ sites. Expression profiling of the normal and tumor cell
      subpopulations encompassing MaSCs and CSCs revealed that the normal stem cell
      compartment is more similar to tumor cells than to their own differentiated
      progenies. Accordingly, Wnt signaling appears to be active in both the normal and
      cancer stem cell compartments, although at different levels. By comparing normal
      with cancer mouse mammary compartments, we identified a MaCSC gene signature able
      to predict outcome in breast cancer in man. Overall, our data indicate that
      constitutive Wnt signaling activation affects self-renewal and differentiation of
      MaSCs leading to metaplasia and basal-like adenocarcinomas. 

PMID- 23955539
TI  - Lung tumor-associated dendritic cell-derived resistin promoted cancer progression
      by increasing Wolf-Hirschhorn syndrome candidate 1/Twist pathway.
AB  - The interaction between tumors and their microenvironments leads to a vicious
      cycle, which strengthens both immune suppression and cancer progression. The
      present study demonstrates for the first time that tumor-associated dendritic
      cells (TADCs) are a source of resistin, which is responsible for increasing lung
      cancer epithelial-to-mesenchymal transition. In addition, large amounts of
      resistin in the condition medium (CM) of TADCs increase cell migration and
      invasion, as well as the osteolytic bone metastatic properties of lung cancer
      cells. Neutralization of resistin from TADC-CM prevents the advanced malignancy
      inducing features of TADC-CM. Significantly elevated levels of resistin have been
      observed in mice transplanted with lung cancer cells, tumor-infiltrating CD11c(+)
      DCs in human lung cancer samples and lung cancer patients' sera. Induction of
      lung cancer progression by TADC-derived resistin is associated with increased
      expression of Wolf-Hirschhorn syndrome candidate 1 (WHSC1), a histone
      methyltransferase. Resistin-induced WHSC1 increases the dimethylation of histone
      3 at lysine 36 and decreases the trimethylation of histone 3 at lysine 27 on the
      promoter of Twist, resulting in an enhancement of the expression of Twist.
      Knockdown of WHSC1 by small interfering RNA transfection significantly decreases
      resistin-mediated cancer progression by decreasing the upregulation of Twist,
      suggesting that WHSC1 plays a critical role in the regulation of Twist by
      epigenetic modification. Furthermore, mice that received antiresistin antibodies
      showed a decreased incidence of cancer development and metastasis. These findings
      suggest that TADC-derived resistin may be a novel candidate in promoting the
      development of lung cancer. 

PMID- 23955541
TI  - Transcription onset of genes critical in liver carcinogenesis is epigenetically
      regulated by methylated DNA-binding protein MBD2.
AB  - We previously delineated genes whose promoters are hypomethylated and induced in
      hepatocellular carcinoma (HCC) patients. The purpose of this study was to
      establish the players that regulate these genes in liver cancer cells. We
      performed chromatin immunoprecipitation with methyl-CpG-binding domain protein 2
      (MBD2), RNA polymerase II (RNA pol II), CCAAT/enhancer-binding protein alpha
      (CEBPA) antibodies and methylated DNA immunoprecipitation in HepG2 liver cancer
      cells treated with scrambled small interfering RNA (siRNA) and siRNA to MBD2 or
      CEBPA. We then hybridized DNA to microarrays spanning the entire coding
      sequences, introns and regulatory regions of several hundred HCC-hypomethylated
      genes. These analyses reveal that MBD2 binds a significant fraction of the
      hypomethylated genes, determines RNA pol II binding and DNA methylation state.
      MBD2 binding can result in promoter activation and hypomethylation or in
      repression. In activated target genes, MBD2 colocalizes with the transcription
      factor CEBPA, and MBD2 binding at these positions is reduced upon CEBPA
      depletion. Significant fraction of MBD2 effects on DNA methylation and
      transcription appears to be indirect since changes occur upon MBD2 depletion in
      genes where no MBD2 binding was detected. Our study delineates the rules
      governing the interaction of MBD2 with its targets and the consequences to RNA
      pol II binding and DNA methylation states. This has important implications for
      understanding the role of DNA methylation in cancer and targeting DNA methylation
      proteins in cancer therapy. 

PMID- 23955542
TI  - Active Solidarity and Its Discontents.
AB  - Traditional welfare states were based on passive solidarity. Able bodied, healthy
      minded citizens paid taxes and social premiums, usually according to a
      progressive taxation logic following the ability to pay principle. Elderly,
      fragile, weak, unhealthy and disabled citizens were taken care of in
      institutions, usually in quiet parts of the country (hills, woods, sea side).
      During the nineteen eighties and nineties of the twentieth century, ideas
      changed. Professionals, patients and policy makers felt that it would be better
      for the weak and fragile to live in mainstream society, rather than be taken care
      of in institutions outside society. This might be cheaper too. Hence policy
      measures were taken to accomplish deinstitutionalization. This article discusses
      the implications of deinstitutionalization for distributive justice. It is argued
      that the weakest among the weak and fragile stand to lose from this operation.
      For able bodied citizens deinstitutionalization entails a move from passive to
      active solidarity. Rather than just pay taxes they have to actively care for and
      help the needy themselves. The move from passive to active solidarity tends to
      take advantage of benevolent citizens and burden the socioeconomically
      disadvantaged. This may be a reason to reconsider the policy move toward
      deinstitutionalization. 

PMID- 23955543
TI  - [Pacemaker dependant and/or repetitive ICD therapies. How to solve the dilemma of
      lead extraction?].
AB  - Bridging pacemaker-dependent patients or patients with repetitive ICD therapies
      after device and lead extraction is often challenging. Temporary pacing by means
      of an active fixation lead connected to an external reusable permanent pacemaker,
      or of a subxiphoidally implanted pacemaker with an epicardial lead is a safe
      option for bridging pacemaker-dependent patients after device and lead
      explantation. The wearable cardioverter defibrillator (WCD; LifeVest((r))) is a
      safe and effective tool for patients who need a continuous monitoring and ICD
      backup after device explantation. 

PMID- 23955544
TI  - First clinical manifestation of Brugada syndrome during pregnancy.
AB  - The role of hormonal changes during pregnancy in Brugada syndrome is unknown.
      Only rare case reports of Brugada syndrome during pregnancy have been published.
      In this article, we describe a patient with first clinical manifestation of
      Brugada syndrome during pregnancy. The definitive diagnosis could only be
      achieved by drug challenge with ajmaline after childbirth because the spontaneous
      typical Brugada-like pattern was absent. Elevated hormone levels during pregnancy
      may increase the risk for arrhythmias in particular cases. 

PMID- 23955545
TI  - Protection of oral hydrogen water as an antioxidant on pulmonary hypertension.
AB  - This study aimed to explore the protective effect of hydrogen as an antioxidant
      on monocrotaline (MCT)-induced pulmonary hypertension (PH). Forty-eight SD rats
      were equally randomized into four groups: SHAM group, MCT group, MCT+Oral-H2
      group and MCT+Inj-H2 group. The results showed that the mean pulmonary arterial
      pressure, right ventricle weight and right ventricular hypertrophy index in MCT
      group were significant higher than those in SHAM group; pulmonary inflammatory
      response, atrial natriuretic factor, 3-nitrityrosine and intercellular adhesion
      molecule-1 were also increased significantly in MCT group. These indexes were
      decreased significantly in both MCT+Oral-H2 group and MCT+Inj-H2 group, which
      indicate Oral-H2 and Inj-H2 have similar effects of preventing the development of
      PH and mitigating RV hypertrophy. The protective effect of hydrogen is associated
      with its antioxidative ability and action of reducing pulmonary inflammatory
      response. While Oral-H2 is more convenient than Inj-H2, Oral-H2 may be ideal for
      clinical use in future. 

PMID- 23955547
TI  - Pharmacokinetics of guanidinosuccinic acid in rat blood and cerebrospinal fluid.
AB  - Guanidinosuccinic acid (GSA) is a uremic toxin, and its excess accumulation in
      the CSF under uremic conditions is thought to produce neural excitotoxicity. It
      is important to understand the manner of GSA distribution/elimination from the
      circulating blood and CSF and its alteration in the presence of renal failure.
      The purpose of this study was to evaluate the kinetics of GSA in the circulating
      blood using a rat model of cisplatin-induced renal failure and GSA transport
      between the circulating blood and CSF. The AUCinf and t1/2 of GSA in cisplatin
      treated rats were approximately 7-fold greater than those in normal rats. The
      CLtot of GSA in cisplatin-treated rats was reduced by 88% compared with normal
      rats, whereas the Vss of GSA did not differ between normal and cisplatin-treated
      rats. These results suggest that the renal elimination of GSA is attenuated in
      cisplatin-treated rats. In normal rats, the elimination clearance of GSA from the
      CSF (15.5 uL/(min.rat)) was found to be 88-fold greater than its blood-to-CSF
      influx clearance (0.176 uL/(min.rat)). Thus, the greater elimination clearance of
      GSA from the CSF, compared with the influx clearance, may contribute to the
      maintenance of a low GSA concentration in the CSF. 

PMID- 23955546
TI  - Predictive value of sphingosine kinase 1 expression in neoadjuvant treatment of
      breast cancer.
AB  - PURPOSE: Sphingolipids play important roles in apoptosis and cell proliferation.
      Sphingosine kinase 1 (SphK1) expression has a prognostic impact in primary breast
      cancer, but its predictive value is currently unknown. METHODS: A total of 112
      breast cancer specimens from a prospective neoadjuvant chemotherapy trial
      (GeparDuo) were studied. Using tissue microarrays of pre-treatment core cut
      biopsies, we determined the expression of SphK1 by immunohistochemistry. The
      upper quartile of the cohort according to an immune reactive score of SphK1 was
      used as cutoff for high expression. RESULTS: We observed a larger number of
      samples with high SphK1 expression among ER-negative cancers (36.8 vs. 20.5 %
      among ER-positive cancers; Fisher test p = 0.073). Eighteen of the 112 patients
      demonstrated a pathological complete response. A significant predictive value for
      pathological complete response was observed for ER negativity (p = 0.003), young
      age (p = 0.037), and high tumor grade (p = 0.049). An increased pCR rate was
      observed in tumors with high SphK1 expression within the luminal subtype (26.7
      vs. 5.8 %; Fisher test p = 0.040). No significant difference in survival was
      detected according to SphK1 expression. CONCLUSIONS: Our results suggest that
      SphK1 may be a predictive factor for pCR after neoadjuvant treatment in luminal
      type breast cancers and warrants further investigation.

PMID- 23955548
TI  - Association between CYP3A5 genotypes in graft liver and increase in tacrolimus
      biotransformation from steroid treatment in living-donor liver transplant
      patients.
AB  - We retrospectively examined whether cytochrome P450 (CYP) 3A5 genotypes are
      associated with high-dose steroid pulse treatment-induced functional gain of
      tacrolimus biotransformation in living-donor liver transplant patients.
      Concentrations of tacrolimus and its 3 primary metabolites, 13-O-demethyl
      tacrolimus (M-I), 31-O-demethyl tacrolimus (M-II), and 15-O-demethyl tacrolimus
      (M-III), were measured in trough blood samples from 18 liver transplant patients,
      by liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS).
      In patients engrafted with a CYP3A5*1-carrying liver but not with a CYP3A5*3/*3
      carrying liver, the concentration/dose ratio of tacrolimus significantly fell
      after therapy, while ratios of M-I/tacrolimus, M-II/tacrolimus, and M
      III/tacrolimus were significantly higher after therapy than before (p = 0.032, p
      = 0.023, and p = 0.0078, respectively). After steroid pulse therapy, the
      concentration of tacrolimus measured by immunoassay was significantly higher than
      that measured by LC-MS/MS in patients engrafted with a CYP3A5*1-carrying liver,
      but not those engrafted with a CYP3A5*3/*3-carrying liver. This suggests that the
      increased ratio of tacrolimus metabolites/tacrolimus can be explained by
      induction of CYP3A5 via high-dose steroid pulse therapy. Further, the
      concentrations of tacrolimus measured by the immunoassays were overestimated,
      partly because of cross-reactivity of the monoclonal antibody they incorporated
      to detect tacrolimus, with the increased metabolites in patients with a CYP3A5*1
      carrying graft liver. 

PMID- 23955549
TI  - Expressions of ER, PR, HER-2, COX-2, and VEGF in primary and relapsed/metastatic
      breast cancers.
AB  - In the present study, we evaluated expressions of estrogen receptor (ER),
      progestin receptor (PR), human epidermal growth factor receptor-2 (HER-2),
      cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF) in
      primary and relapsed/metastatic breast cancers to elucidate the clinical
      significance of these markers. The markers were evaluated by immunohistochemistry
      in specimens of 50 patients with primary or metastatic breast cancer. Positive
      rates of ER were significantly (p = 0.002) higher in primary versus
      relapsed/metastatic breast cancer (70 vs. 38 %, respectively). The VEGF positive
      expression rates were also significantly higher in primary versus metastatic
      cancer (82 vs. 38 %, respectively; p < 0.001). By contrast, positive rates of HER
      2 and COX-2 were not significantly different between different types of cancer.
      COX-2 correlated with HER-2 expression in both primary and relapsed/metastatic
      focuses of breast cancer. COX-2 also correlated with VEGF expression in primary
      breast cancer. Expressions of ER, PR, HER2, and COX-2 did not correlate between
      primary and relapsed/metastatic breast cancers, indicating that the treatment
      decision should be made according to the status of these markers in
      relapsed/metastatic focuses. The total change rates of ER, PR, HER-2, COX-2, and
      VEGF were 26, 18, 10, 30, and 58 %, respectively. In conclusion, HER-2 and COX-2,
      along with VEGF, appear to play a role in the development and progression of
      breast cancer. In addition, all of the studied markers may serve as indicators of
      prognosis.

PMID- 23955550
TI  - Myeloperoxidase deficiency in mice exacerbates lung inflammation induced by
      nonviable Candida albicans.
AB  - OBJECTIVE: This study aimed to evaluate the effect of myeloperoxidase (MPO)
      deficiency on lung inflammation induced by nonviable Candida albicans (nCA).
      METHODS: Mice were inoculated intranasally with nCA, and accumulation of
      neutrophils and macrophages in the bronchoalveolar lavage fluid was analyzed by
      flow cytometry. The levels of macrophage inflammatory protein 2 (MIP-2),
      keratinocyte-derived chemokine (KC), tumor necrosis factor (TNF)-alpha, and
      interleukin (IL)-1beta in the lung were measured by ELISA. Production of MIP-2
      and KC from neutrophils and macrophages was quantified in vitro. MIP-2 mRNA
      expression in the neutrophils was analyzed by real-time reverse transcription
      PCR, and the extent of phosphorylation of ERK1/2 and Syk in the neutrophils was
      analyzed by Western blotting. RESULTS: The MPO(-/-) mice that received nCA showed
      more severe pneumonia than wild-type mice. Within 12 h of nCA administration,
      MPO(-/-) mice had significantly higher numbers of alveolar neutrophils and
      increased production of MIP-2 and KC relative to the responses seen in wild-type
      mice. Neutralization of MIP-2 and KC in vivo significantly reduced neutrophil
      infiltration. In vitro, production of MIP-2, but not that of KC, was enhanced in
      the nCA-stimulated neutrophils from MPO(-/-) mice, concomitant with up-regulation
      of Syk and ERK1/2. At 1 and 3 days after nCA administration, MPO(-/-) mice had
      significantly higher lung concentrations of TNF-alpha and IL-1beta than wild-type
      mice. CONCLUSION: Pulmonary administration of nCA produced an altered
      inflammatory response in MPO(-/-) mice relative to wild-type mice. Enhanced MIP-2
      production by MPO(-/-) neutrophils may at least partly contribute to exacerbated
      inflammation in mutant mice.

PMID- 23955553
TI  - Controllable Mono-/Dialkenylation of Benzyl Thioethers through Rh-Catalyzed Aryl
      C-H Activation.
AB  - Under solvent control: Benzyl thioethers were alkenylated in excellent yields
      with broad substrate scope and the selectivity (mono- vs. disubstituted product)
      was controlled by the solvent and ratio of reactants. Sequential alkenylation
      with two different alkenes was also carried out in a one-pot process. In
      addition, the thioether directing group was removed in a one-pot process with
      simultaneous hydrogenation of the double bond to give the toluene derivatives. 

PMID- 23955552
TI  - Intermittent tri-weekly docetaxel plus bicalutamide in patients with castration
      resistant prostate cancer: a single-arm prospective study using a historical
      control for comparison.
AB  - Whether continuous docetaxel (DTX) chemotherapy offers an advantage over
      intermittent therapy for castration-resistant prostate cancer (CRPC) is unknown.
      In this study, we evaluated the efficacy, toxicity and quality of life (QoL) of
      intermittent tri-weekly DTX with bicalutamide in CRPC. Forty-two patients (group
      A) with CRPC were enrolled. The patients received intravenous DTX (75 mg m(-2))
      once tri-weekly with oral bicalutamide (50 mg) once daily. Patients had a DTX
      holiday when the prostate-specific antigen (PSA) level declined >=50%. DTX was
      restarted in patients with a PSA increase >=25%. Sixty patients (group B) who had
      matching characteristics and had continuously received DTX without bicalutamide
      for 10-12 cycles were also enrolled. There were no statistically significant
      differences in progression-free survival (8 months vs. 9 months, P=0.866) or
      overall survival (19 months vs. 21 months, P=0.753) between groups A and B;
      however, the proportions of patients in group A with all grades of neutropenia
      (33% vs. 58%, P=0.013) and nausea/vomiting (11% vs. 29%, P=0.024) were
      significantly less compared to group B. A significant improvement in the global
      health and fatigue scores was recorded for group A post-chemotherapy compared to
      pre-chemotherapy (P<0.05). The fatigue, nausea/vomiting and appetite loss scores
      in group B were increased post-chemotherapy compared to pre-chemotherapy
      (P<0.05). In conclusion, intermittent tri-weekly DTX plus bicalutamide is well
      tolerated and has the potential to achieve comparable disease control with an
      improvement in QoL for patients with CRPC.

PMID- 23955554
TI  - Ethoxyquin prevents chemotherapy-induced neurotoxicity via Hsp90 modulation.
AB  - OBJECTIVE: Peripheral neurotoxicity is a major dose-limiting side effect of many
      chemotherapeutic drugs. Currently there are no effective disease-modifying
      therapies for chemotherapy-induced peripheral neuropathies, but these side
      effects of chemotherapy are potentially ideal targets for development of
      neuroprotective therapies, because candidate drugs can be co- or preadministered
      before the injury to peripheral axons takes place. METHODS: We used a phenotypic
      drug screening approach to identify ethoxyquin as a potential neuroprotective
      drug and carried out additional biochemical experiments to identify its mechanism
      of action. RESULTS: We validated the screening results with ethoxyquin and its
      derivatives and showed that they prevented paclitaxel-induced peripheral
      neuropathy without blocking paclitaxel's ability to kill tumor cells.
      Furthermore, we demonstrated that ethoxyquin acts by modulating the chaperone
      activity of heat shock protein 90 (Hsp90) and blocking the binding of 2 of its
      client proteins, ataxin-2 and Sf3b2. Ethoxyquin-induced reduction in levels of
      both of these proteins resulted in prevention of axonal degeneration caused by
      paclitaxel. INTERPRETATION: Ethoxyquin and its novel derivatives as well as other
      classes of small molecules that act as Hsp90 modulators may offer a new
      opportunity for development of drugs to prevent chemotherapy-induced axonal
      degeneration.

PMID- 23955555
TI  - Moderate compared to low dietary intake of trans-fatty acids impairs strength of
      old and aerobic capacity of young SAMP8 mice in both sexes.
AB  - The senescence accelerated SAMP8 mouse is a model for sarcopenia and provides an
      opportunity to study the effects of lifelong dietary composition on the loss of
      physical function with age. We studied the effects of trans-fatty acids (2 % of
      total energy, TFA diet) on the loss of strength and aerobic exercise capacity
      (VO2peak) with age. SAMP8 mice were studied at two ages (young, 25 weeks; old, 60
      weeks) and on two diets (control vs TFA). Body composition, grip strength,
      VO2peak, blood metabolites, and biochemical parameters were assessed. Body
      weight, fat mass, and body fat percentage all increased with age (p < 0.05) but
      were not significantly impacted by diet. There was a significant age-related
      decline in total grip strength as well as that normalized to fat-free mass (FFM)
      (p < 0.05) with a further decrease at old age in these metrics of strength on the
      TFA diet vs control diet (p < 0.05). Total VO2peak exhibited no change with age
      or diet, but when normalized to FFM, VO2peak exhibited age and TFA-related
      declines (p < 0.05). Intramuscular triacylglycerol (p < 0.05) and collagen
      content (p < 0.05) significantly increased with age, while blood triacylglycerol
      was increased by the TFA diet (p < 0.05). These data further characterize the
      SAMP8 mouse as a model for sarcopenia and indicate that dietary fatty acid
      composition can impact the degree of this age-related loss of physical function.

PMID- 23955556
TI  - Outcomes and risk stratification for severe ARDS treated with ECMO.

PMID- 23955557
TI  - Relationship between stress ankle radiographs and injured ligaments on MRI.
AB  - OBJECTIVE: This study was performed to investigate the relationship between the
      injured lateral ankle ligaments on MRI and stress ankle radiographs. MATERIALS
      AND METHODS: Two hundred and twenty-nine consecutive patients (mean age 35.5
      years, SD 14.6 years; 136 males and 93 females) that underwent ankle stress
      radiographs and MRI for lateral ankle instability were included. Tibiotalar tilt
      angle and anterior translation of talus were measured on stress ankle
      radiographs. Degree of lateral ligaments (anterior talofibular, calcaneofibular,
      and posterior talofibular) and deltoid ligament injuries were evaluated and
      scored as intact (0), partial injury (1), and complete injury (2) on MR images.
      Effusion of ankle joint was also recorded. The effects of gender, age, injuries
      of ligaments, and ankle joint effusion on stress radiographs were statistically
      analyzed. RESULTS: Gender (p = 0.010), age (p = 0.020), and anterior talofibular
      ligament (ATFL) injury (p < 0.001) were the factors significantly affecting
      tibiotalar tilt angle. Posterior talofibular ligament (PTFL) injury (p = 0.014)
      was found to be the only significant factor affecting the anterior translation on
      the anterior drawer radiographs. CONCLUSIONS: ATFL injury and PTFL injury on MRI
      significantly affected tibiotalar tilt angle and anterior drawer on stress
      radiographs. Other factors, such as age and gender, need to be considered in
      evaluating radiographic lateral ankle instability.

PMID- 23955558
TI  - Characterisation and evaluation of paramagnetic fluorine labelled glycol chitosan
      conjugates for (19)F and (1)H magnetic resonance imaging.
AB  - Medium molecular weight glycol chitosan conjugates have been prepared, linked by
      an amide bond to paramagnetic Gd(III), Ho(III) and Dy(III) macrocyclic complexes
      in which a trifluoromethyl reporter group is located 6.5 A from the paramagnetic
      centre. The faster relaxation of the observed nucleus allows modified pulse
      sequences to be used with shorter acquisition times. The polydisperse materials
      have been characterised by gel permeation chromatography, revealing an average
      molecular weight on the order of 13,800 (Gd), 14,600 (Dy) and 16,200 (Ho),
      consistent with the presence of 8.5, 9.5 and 13 complexes, respectively. The
      gadolinium conjugate was prepared for both a q = 1 monoamide tricarboxylate
      conjugate (r1p 11.2 mM(-1) s(-1), 310 K, 1.4 T) and a q = 0 triphosphinate
      system, and conventional contrast-enhanced proton MRI studies at 7 T were
      undertaken in mice bearing an HT-29 or an HCT-116 colorectal tumour xenograft (17
      MUmol/kg). Enhanced contrast was observed following injection in the tail vein in
      tumour tissue, with uptake also evident in the liver and kidney with a tumour-to
      liver ratio of 2:1 at 13 min, and large amounts in the kidney and bladder
      consistent with predominant renal clearance. Parallel experiments observing the
      (19)F resonance in the holmium conjugate complex using a surface coil did not
      succeed owing to its high R2 value (750 Hz, 7 T). However, the fluorine signal in
      the dysprosium triphosphinate chitosan conjugate [R1/R2 = 0.6 and R1 = 145 Hz (7
      T)] was sharper and could be observed in vivo at -65.7 ppm, following intravenous
      tail vein injection of a dose of 34 MUmol/kg.

PMID- 23955559
TI  - Saltatory remodeling of Hox chromatin in response to rostrocaudal patterning
      signals.
AB  - Hox genes controlling motor neuron subtype identity are expressed in rostrocaudal
      patterns that are spatially and temporally collinear with their chromosomal
      organization. Here we demonstrate that Hox chromatin is subdivided into discrete
      domains that are controlled by rostrocaudal patterning signals that trigger
      rapid, domain-wide clearance of repressive histone H3 Lys27 trimethylation
      (H3K27me3) polycomb modifications. Treatment of differentiating mouse neural
      progenitors with retinoic acid leads to activation and binding of retinoic acid
      receptors (RARs) to the Hox1-Hox5 chromatin domains, which is followed by a rapid
      domain-wide removal of H3K27me3 and acquisition of cervical spinal identity. Wnt
      and fibroblast growth factor (FGF) signals induce expression of the Cdx2
      transcription factor that binds and clears H3K27me3 from the Hox1-Hox9 chromatin
      domains, leading to specification of brachial or thoracic spinal identity. We
      propose that rapid clearance of repressive modifications in response to transient
      patterning signals encodes global rostrocaudal neural identity and that
      maintenance of these chromatin domains ensures the transmission of positional
      identity to postmitotic motor neurons later in development. 

PMID- 23955560
TI  - Balanced cortical microcircuitry for maintaining information in working memory.
AB  - Persistent neural activity in the absence of a stimulus has been identified as a
      neural correlate of working memory, but how such activity is maintained by
      neocortical circuits remains unknown. We used a computational approach to show
      that the inhibitory and excitatory microcircuitry of neocortical memory-storing
      regions is sufficient to implement a corrective feedback mechanism that enables
      persistent activity to be maintained stably for prolonged durations. When
      recurrent excitatory and inhibitory inputs to memory neurons were balanced in
      strength and offset in time, drifts in activity triggered a corrective signal
      that counteracted memory decay. Circuits containing this mechanism temporally
      integrated their inputs, generated the irregular neural firing observed during
      persistent activity and were robust against common perturbations that severely
      disrupted previous models of short-term memory storage. These results reveal a
      mechanism for the accumulation and storage of memories in neocortical circuits
      based on principles of corrective negative feedback that are widely used in
      engineering applications. 

PMID- 23955561
TI  - Probabilistic brains: knowns and unknowns.
AB  - There is strong behavioral and physiological evidence that the brain both
      represents probability distributions and performs probabilistic inference.
      Computational neuroscientists have started to shed light on how these
      probabilistic representations and computations might be implemented in neural
      circuits. One particularly appealing aspect of these theories is their
      generality: they can be used to model a wide range of tasks, from sensory
      processing to high-level cognition. To date, however, these theories have only
      been applied to very simple tasks. Here we discuss the challenges that will
      emerge as researchers start focusing their efforts on real-life computations,
      with a focus on probabilistic learning, structural learning and approximate
      inference. 

PMID- 23955562
TI  - A systematic review of the relationship between physical activities in sports or
      daily life and postural sway in upright stance.
AB  - BACKGROUND: In many sports, maintaining balance is necessary to compete at a high
      level. Also, in many health problems, balance is impaired. Postural sway (PS) is
      often used as an indicator of upright balance control, and physical activity (PA)
      might enhance balance control. However, the relationship between PS and PA has
      never been systematically reviewed. OBJECTIVE: Our objective was to summarize the
      evidence regarding the relationship between PS in upright bipedal and unipedal
      standing and PA. METHODS: We conducted a literature search in MEDLINE, EmBase,
      CINAHL, the Cochrane Database, and PEDro, up to March 2012, with no limit on the
      starting date. Characteristics and methodological aspects of each article were
      extracted by two reviewers. We used centre of pressure (CoP) velocity, and
      variables related to the CoP area, to compare studies. RESULTS: A total of 39
      articles were reviewed from an initial yield of 2,058. Of these 39 studies, 37
      used a comparative design, one was a cohort study, and one was a randomized
      controlled trial. CONCLUSION: The main conclusion was that in general, sport
      practitioners sway less than controls, and high-level athletes sway less than low
      level athletes. Additionally, we identified specific effects dependent on the use
      of vision, sport-specific postures, and frequency and duration of the (sports)
      activity. PS in unperturbed bipedal stance appears to have limited sensitivity to
      detect subtle differences between groups of healthy people.

PMID- 23955563
TI  - Erratum to: the acaricidal efficacy of peracetic acid and deltamethrin against
      the fowl tick, Argas persicus, infesting laying hens.
AB  - The fowl tick, Argas persicus (Oken), is of veterinary importance as a parasite
      of poultry and wild birds. The antitick efficacy, in vitro and in vivo, of
      peracetic acid (PAA) and deltamethrin (DMT) was tested separately against A.
      persicus through the dipping technique. PAA (0.5%) was highly efficient against
      soft tick larvae (A. persicus), resulting in 100 % mortality after 2 min. The
      lethal concentrations LC50 and LC95 were 0.310 and 0.503 %, respectively. The
      lethal time values LT50 and LT95 were 5.34 and 40.00 min, respectively, after
      treatment with PAA (0.25%). Two minutes after exposure to DMT, LC50 and LC95
      values were 0.0033 and 0.0052% (33.204 and 51.527 mg/L), respectively. The LT50
      and LT95 values were 27.03 and 305.46 min, respectively, after treatment with
      0.0025% DMT (25 mg/L). After dipping in PAA (0.5%), the chickens did not show
      respiratory signs or inflammation on the eyes and/or skin. By contrast, temporary
      coughing, sneezing, and ocular inflammations without dermatitis were observed in
      chickens dipped in DMT (0.005 % or 50 mg /L). Seven days posttreatment (PT), the
      reduction in the percentages of A. persicus infesting laying hens were 99.15 and
      63.42% after dipping in PAA and DMT, respectively. However, complete elimination
      of the number of ticks occurred after 28 days PT with DMT. PAA inhibits molting
      effectively (28%) when compared with that of DMT (52%). Results indicated that
      PAA is a more potent and promising acaricide against A. persicus (in vitro and in
      vivo) than DMT.

PMID- 23955564
TI  - Remarks on the validity of Myxobolus ampullicapsulatus and Myxobolus honghuensis
      (Myxozoa: Myxosporea) based on SSU rDNA sequences.
AB  - In the present study, we isolated three populations of Myxobolus
      ampullicapsulatus from the gills of crucian carp, Carassius auratus auratus, two
      from Yongchuan, Chongqing area and one from Poyang Lake, Jiangxi area, China,
      sequenced their complete small subunit ribosome RNA gene, analyzed their genetic
      distance and gene similarity, and explored their relationship based on Bayesian
      inference and maximum likelihood analyses of their small subunit ribosomal DNA.
      The results combined with their morphological characteristics suggest that M.
      ampullicapsulatus infecting the gills and pharynx of allogynogenetic gibel carp,
      Carassius auratus gibelio, should be Myxobolus honghuensis. This study highlights
      the importance of DNA sequence comparisons for distinguishing Myxobolus species
      and indicates that the intra-species identification for the two Myxobolus species
      mentioned in the present research should be less than ten variation sites. In
      morphology, M. honghuensis Liu et al. (2012) parasitic on the gills of C. auratus
      auratus (goldfish) was collected from Chongqing area, and its mature spore was
      16.5-19.5 * 8.5-10.0 MUm in size, polar capsule was 7.0-10.0 * 2.5-4.0 MUm in
      size, and polar filament had 9-10 coils. M. honghuensis Liu et al. (2012)
      isolated from the pharynx of C. auratus gibelio was sampled in Hubei area, and
      its mature spore was 15.1-19.5 * 9.0-11.3 MUm in size, polar capsule was 7.9-8.1
      * 3.0-4.5 MUm in size, and polar filament had 7-8 coils. 

PMID- 23955565
TI  - TERT promoter mutations in primary and secondary glioblastomas.
AB  - Telomerase reverse transcriptase (TERT) is up-regulated in a variety of human
      neoplasms. Mutations in the core promoter region of the TERT gene, which
      increases promoter activity, have been reported in melanomas and a variety of
      human neoplasms, including gliomas. In the present study, we screened for TERT
      promoter mutations by direct DNA sequencing in a population-based collection of
      358 glioblastomas. TERT promoter mutations (C228T, C250T) were detected in 55 %
      glioblastomas analysed. Of these, 73 % had a C228T mutation, and 27 % had a C250T
      mutation; only one glioblastoma had both C228T and C250T mutations. TERT promoter
      mutations were significantly more frequent in primary (IDH1 wild-type)
      glioblastomas (187/322; 58 %) than in secondary (IDH1 mutated) glioblastomas
      (10/36, 28 %; P = 0.0056). They showed significant inverse correlations with IDH1
      mutations (P = 0.0056) and TP53 mutations (P = 0.043), and a significant positive
      correlation with EGFR amplification (P = 0.048). Glioblastoma patients with TERT
      mutations showed a shorter survival than those without TERT mutations in
      univariate analysis (median, 9.3 vs. 10.5 months; P = 0.015) and multivariate
      analysis after adjusting for age and gender (HR 1.38, 95 % CI 1.01-1.88, P =
      0.041). However, TERT mutations had no significant impact on patients' survival
      in multivariate analysis after further adjusting for other genetic alterations,
      or when primary and secondary glioblastomas were separately analysed. These
      results suggest that the prognostic value of TERT mutations for poor survival is
      largely due to their inverse correlation with IDH1 mutations, which are a
      significant prognostic marker of better survival in patients with secondary
      glioblastomas.

PMID- 23955566
TI  - Message from the President return on investment: debunking a myth.

PMID- 23955567
TI  - Nonsolvents-induced swelling of poly(methyl methacrylate) nanoparticles.
AB  - Polymer nanoparticles have been used in a wide variety of applications. In most
      of these applications, they are generally dispersed in a non-solvent. However,
      the effect of the non-solvent on the structure, physical properties and function
      of the nanoparticles has not yet ever taken into account. In this study,
      monodispersed poly(methyl methacrylate) (PMMA) nanoparticles were prepared by a
      surfactant-free emulsion polymerization. The PMMA nanoparticles were dispersed in
      water and in methanol, both typical non-solvents for PMMA, so that we could
      discuss the effect of the non-solvent on the nanoparticles. Dynamic light
      scattering measurements revealed that the hydrodynamic radius of the PMMA
      nanoparticles in methanol was larger than the same PMMA dispersed in water. Their
      DLS values were also larger than the radius of the nanoparticles measured by
      atomic force microscopy. When pyrene was dispersed in methanol with the PMMA
      nanoparticles, it was incorporated into the nanoparticles. These results clearly
      indicate that non-solvent molecules can be sorbed into polymer nanoparticles
      because the area of the interface, where polymer segments might be dissolved into
      liquid phases, as the total volume is quite larger for such nanoparticles.
      Therefore, based on our findings, it can be arguably established that the present
      assumption for a polymer not to be swollen in its non-solvent is not necessarily
      true. 

PMID- 23955568
TI  - Efficient metal-free synthesis of various pyrido[2',1':2,3]imidazo- [4,5
      b]quinolines.
AB  - Dancing with diversity: The synthesis of diverse pyrido[2',1':2,3]imidazo[4,5
      b]quinolines bearing several substitution patterns was developed based on
      combining a multicomponent reaction (Groebke-Blackburn-Bienayme reaction) with an
      original cyclization as a secondary transformation (see scheme; DBU = 1,8
      diazabicyclo[5.4.0]undec-7-ene).

PMID- 23955570
TI  - Tetraspanin TSPAN12 regulates tumor growth and metastasis and inhibits beta
      catenin degradation.
AB  - Ablation of tetraspanin protein TSPAN12 from human MDA-MB-231 cells significantly
      decreased primary tumor xenograft growth, while increasing tumor apoptosis.
      Furthermore, TSPAN12 removal markedly enhanced tumor-endothelial interactions and
      increased metastasis to mouse lungs. TSPAN12 removal from human MDA-MB-231 cells
      also caused diminished association between FZD4 (a key canonical Wnt pathway
      receptor) and its co-receptor LRP5. The result likely explains substantially
      enhanced proteosomal degradation of beta-catenin, a key effecter of canonical Wnt
      signaling. Consistent with disrupted canonical Wnt signaling, TSPAN12 ablation
      altered expression of LRP5, Naked 1 and 2, DVL2, DVL3, Axin 1, and GSKbeta3
      proteins. TSPAN12 ablation also altered expression of several genes regulated by
      beta-catenin (e.g. CCNA1, CCNE2, WISP1, ID4, SFN, ME1) that may help to explain
      altered tumor growth and metastasis. In conclusion, these results provide the
      first evidence for TSPAN12 playing a role in supporting primary tumor growth and
      suppressing metastasis. TSPAN12 appears to function by stabilizing FZD4-LRP5
      association, in support of canonical Wnt-pathway signaling, leading to enhanced
      beta-catenin expression and function. 

PMID- 23955571
TI  - Chronic epilepsy due to low grade temporal lobe tumors and due to hippocampal
      sclerosis: do they differ in post-surgical outcome?
AB  - Chronic seizures as a presenting feature of low grade temporal lobe gliomas and
      hippocampal sclerosis (HS) are reported to have similar outcomes although the
      prognostic indicators may not be the same. This study seeks to identify the
      variables that are associated with poor surgical outcome in both conditions. A
      retrospective analysis from our epilepsy data base was performed. All low-grade
      temporal lobe gliomas were selected and relevant variables were compared to the
      same variables in HS patients. There were 34 tumors (out of 233 cases of chronic
      temporal lobe epilepsy = 14.6 %) with a mean age of onset of 19 years, and the
      preoperative duration was 12.3 years. When compared to 120 HS patients both of
      these factors were significantly different (p < 0.001). Age at the time of
      surgery for tumors was 31.08 (p = 0.5). Tumors were left sided in 20 patients. In
      tumor cases amygdala resection was complete in 75 %, for hippocampus 24 % were
      complete and 39 % partial. Astrocytoma, ganglioglioma and oligodendroglioma
      constituted 80 % of tumor cases. Good outcome (Engel's Class I) was achieved in
      88.2 % of tumor cases and 71 % of HS cases while poor outcome (Class III + IV)
      was seen in 5.9 and 16.7 % respectively. The follow up period for the two groups
      was not significantly different. In multivariate logistic regression analysis,
      the groups differed significantly in preoperative delay (between diagnosis and
      surgery) and in epilepsy outcome. Chronic temporal lobe epilepsy due to low-grade
      tumors had significantly better surgical outcome with considerably less
      preoperative delay. The age of onset of seizures was younger in HS patients but a
      delay in surgical treatment was significantly longer. Given that the diagnosis of
      treatment-resistant TLE secondary to HS can be established after two failed AED
      trials at optimal doses, shortening the interval between diagnosis and surgery
      may improve epilepsy outcome.

PMID- 23955572
TI  - Ongoing and prolonged response in adult low-grade gliomas treated with
      radiotherapy.
AB  - The aim of the present study was to evaluate the impact of first-line
      radiotherapy on low-grade gliomas (LGGs) growth kinetics. The mean tumor diameter
      (MTD) of 39 LGGs was retrospectively measured on serial magnetic resonance images
      before (n = 16) and after radiotherapy onset (n = 39). After radiotherapy, a
      decrease of the MTD was observed in 37 patients. Median duration of the MTD
      decrease was 1.9 years (range 0-8.1 years). According to RANO criteria, the rates
      of partial and minor responses were 15 and 28 % at the first evaluation after
      radiotherapy and 36 and 34 % at the time of maximal MTD decrease. The presence of
      a 1p19q codeletion and the absence of p53 expression were associated with longer
      durations of MTD decrease (5.3 vs 1 years, p = 0.02 and 2.4 vs 1.8 years, p =
      0.05, respectively) while no association was observed between IDH1-R132H
      expression and duration of MTD decrease. In most patients, MTD decrease after
      radiotherapy occurred in two phases: an initial phase of rapid MTD decrease
      followed by a second phase of slower MTD decrease. Patients with a high rate of
      MTD decrease during the initial phase (>7 mm/year) had both a shorter duration of
      response (1.9 vs 5.3 years, p = 0.003) and a shorter overall survival (5.5 vs
      11.6 years, p = 0.0004). LGGs commonly display a prolonged and ongoing volume
      decrease after radiotherapy. However, patients who respond rapidly should be
      carefully monitored because they are at a higher risk of rapid progression.

PMID- 23955573
TI  - Sirtuin-2 activity is required for glioma stem cell proliferation arrest but not
      necrosis induced by resveratrol.
AB  - Glioblastomas, the most common form of primary brain tumors, are the fourth cause
      of death by cancer in adults. Increasing evidences suggest that glioblastoma
      resistance to existing radio- and chemotherapies rely on glioblastoma stem cells
      (GSCs). GSCs are endowed with a unique combination of stem-like properties alike
      to normal neural stem cells (NSCs), and of tumor initiating properties. The
      natural polyphenol resveratrol is known to exert opposite actions on neural cells
      according to their normal or cancerous status. Here, we used resveratrol to
      explore the molecular mechanisms differing between GSCs and NSCs. We observed a
      dual action of resveratrol on GSCs: resveratrol blocked GSC proliferation up to
      150 MUM and induced their necrosis at higher doses. On the opposite, resveratrol
      had no effect on NSC behavior. To determine the mechanisms underlying resveratrol
      effects, we focused our attention on the family of NAD-dependent deacetylases
      sirtuins (SIRT). A member of this family, SIRT1, has been repetitively shown to
      constitute a preferential resveratrol target, at least in normal cells. Western
      blot analysis showed that SIRT1 and SIRT3 were expressed by both GSCs and NSCs
      whereas SIRT2 expression was restricted to GSCs. Pharmacological blockade of
      SIRT2 activity or down-regulation of SIRT2 expression with siRNAs counteracted
      the inhibitory effect of resveratrol on cell proliferation. On the contrary,
      inhibition of SIRT2 activity or expression did not counteract GSC necrosis
      observed in presence of high doses of resveratrol. Our results highlight SIRT2 as
      a novel target for altering GSC properties.

PMID- 23955574
TI  - Neural crest stem cell-specific deletion of the Pygopus2 gene modulates hair
      follicle development.
AB  - We show that neural crest stem cells affect mouse hair follicle development.
      During embryogenesis hair follicle induction is regulated by complex reciprocal
      and functionally redundant signals between epidermis and dermis, which remain to
      be fully understood. Canonical Wnt signalling is a hallmark of neural crest cells
      and also a prerequisite for hair follicle induction prior to hair placode
      formation in the epidermis. As neural crest stem cells invade the epidermis
      during early embryonic development we aimed at determining whether neural crest
      cells affect hair follicle development. To attenuate, but not silence, canonical
      Wnt signalling specifically in neural crest cells, we analyzed Wnt1-cre(+/
      )::Pygo2(-/-) mice in which the beta-catenin co-activator gene, Pygopus 2
      (Pygo2), is deleted specifically in neural crest cells. Both, hair density and
      hair thickness were reduced in mutant mice. Furthermore, hair development was
      delayed and the relative ratio of hair types was affected. There was a decrease
      in zig-zag hairs and an increase in awl hairs. Mouse neural crest stem cells
      expressed ectodysplasin, an essential effector in the formation of zig-zag hair.
      Taken together, our data support the novel notion that neural crest cells are
      involved in the earliest stages of hair follicle development. 

PMID- 23955575
TI  - Targeting head and neck cancer stem cells to overcome resistance to photon and
      carbon ion radiation.
AB  - Although promising new radiation therapy techniques such as hadrontherapy are
      currently being evaluated in the treatment of head and neck malignancies, local
      control of head and neck squamous cell carcinoma (HNSCC) remains low. Here, we
      investigated the involvement of cancer stem-like cells (CSCs) in a radioresistant
      HNSCC cell line (SQ20B). Stem-like cells
      SQ20B/SidePopulation(SP)/CD44(+)/ALDH(high) were more resistant to both photon
      and carbon ion irradiation compared with non-CSCs. This was confirmed by a BrdU
      labeling experiment, which suggests that CSCs were able to proliferate and to
      induce tumorigenicity after irradiation. SQ20B/SP/CD44(+)/ALDH(high) were capable
      of an extended G2/M arrest phase in response to photon or carbon ion irradiation
      compared with non-CSCs. Moreover, our data strongly suggest that resistance of
      CSCs may result from an imbalance between exacerbated self-renewal and
      proliferative capacities and the decrease in apoptotic cell death triggering. In
      order to modulate these processes, two targeted pharmacological strategies were
      tested. Firstly, UCN-01, a checkpoint kinase (Chk1) inhibitor, induced the
      relapse of G2/M arrest and radiosensitization of SQ20B-CSCs. Secondly, all-trans
      retinoic acid (ATRA) resulted in an inhibition of ALDH activity, and induction of
      the differentiation and radiosensitization of SQ20B/SP/CD44(+)/ALDH(high) cells.
      The combination of ATRA and UCN-01 treatments with irradiation drastically
      decreased the surviving fraction at 2Gy of SQ20B-CSCs from 0.85 to 0.38 after
      photon irradiation, and from 0.45 to 0.21 in response to carbon ions. Taken
      together, our results suggest that the combination of UCN-01 and ATRA represent a
      promising pharmacological-targeted strategy that significantly sensitizes CSCs to
      photon or carbon ion radiation. 

PMID- 23955577
TI  - The quantification of body fluid allostasis during exercise.
AB  - The prescription of an optimal fluid intake during exercise has been a
      controversial subject in sports science for at least the past decade. Only
      recently have guidelines evolved from 'blanket' prescriptions to more
      individualised recommendations. Currently the American College of Sports Medicine
      advise that sufficient fluid should be ingested to ensure that body mass (BM)
      loss during exercise does not exceed >2 % of starting BM so that exercise
      associated medical complications will be avoided. Historically, BM changes have
      been used as a surrogate for fluid loss during exercise. It would be helpful to
      accurately determine fluid shifts in the body in order to provide physiologically
      appropriate fluid intake advice. The measurement of total body water via D2O is
      the most accurate measure to detect changes in body fluid content; other methods,
      including bioelectrical impedance, are less accurate. Thus, the aim of this
      review is to convey the current understanding of body fluid allostasis during
      exercise when drinking according to the dictates of thirst (ad libitum). This
      review examines the basis for fluid intake prescription with the use of BM, the
      concepts of 'voluntary and involuntary dehydration' and the major routes by which
      the body gains and loses fluid during exercise. 

PMID- 23955576
TI  - Molecular mechanisms controlling the cell cycle in embryonic stem cells.
AB  - Embryonic stem (ES) cells are originated from the inner cell mass of a blastocyst
      stage embryo. They can proliferate indefinitely, maintain an undifferentiated
      state (self-renewal), and differentiate into any cell type (pluripotency). ES
      cells have an unusual cell cycle structure, consists mainly of S phase cells, a
      short G1 phase and absence of G1/S checkpoint. Cell division and cell cycle
      progression are controlled by mechanisms ensuring the accurate transmission of
      genetic information from generation to generation. Therefore, control of cell
      cycle is a complicated process, involving several signaling pathways. Although
      great progress has been made on the molecular mechanisms involved in the
      regulation of ES cell cycle, many regulatory mechanisms remain unknown. This
      review summarizes the current knowledge about the molecular mechanisms regulating
      the cell cycle of ES cells and describes the relationship existing between cell
      cycle progression and the self-renewal. 

PMID- 23955578
TI  - Single-walled carbon nanotubes induce cell death and transcription of TNF-alpha
      in macrophages without affecting nitric oxide production.
AB  - Single-walled carbon nanotubes (SWCNTs) are potent nanomaterials that have
      diverse shapes and features. The utilization of these molecules for drug delivery
      is being investigated; thus, it is important to determine whether they alter
      immune responses against pathogens. In this study, we show that macrophages
      treated with a mixture of lipopolysaccharide and SWCNTs produced normal levels of
      nitric oxide and inducible nitric oxide synthase mRNA. However, these treatments
      induced cell death, presumably via necrosis. In addition, treating cells with
      SWCNTs induced the expression of tumor necrosis factor-alpha mRNA, a potent pro
      inflammatory cytokine. These results suggest that SWCNTs may influence immune
      responses, which could result in unexpected effects following their
      administration for the purpose of drug delivery.

PMID- 23955579
TI  - Bilateral hip imaging at 7 Tesla using a multi-channel transmit technology:
      initial results presenting anatomical detail in healthy volunteers and
      pathological changes in patients with avascular necrosis of the femoral head.
AB  - OBJECTIVE: To evaluate 7-T MRI of both hips using a multi-channel transmit
      technology to compensate for inherent B1 inhomogeneities in volunteers and
      patients with avascular necrosis of the femoral head. MATERIALS AND METHODS: A
      self-built, eight-channel transmit-receive coil was utilized for B1 modification
      at 7 T. Two shim modes (individual shim vs. CP2+ mode) were initially compared
      and the best shim result was used for all further imaging. Robustness of
      sequences against B1 inhomogeneities, appearance of anatomic and pathologic
      changes of the femoral heads of MEDIC, DESS, PD/T2w TSE, T1w TSE, and STIR
      sequences at 7 T were evaluated in 12 subjects on a four-point scale (1-4): four
      male volunteers and eight patients (seven males, one female) suffering from
      avascular necrosis treated by advanced core decompression. RESULTS: Successful
      MRI of both femoral heads was achieved in all 12 subjects. CP2+ mode proved
      superior in ten of 12 cases. DESS proved most robust against B1 inhomogeneity.
      Anatomical details (labrum, articular cartilage) were best depicted in PDw,
      MEDIC, and DESS, while for depiction of pathological changes PDw, DESS (0.76
      mm(3)) and T1w were superior. CONCLUSIONS: Our initial results of ultra-high
      field hip joint imaging demonstrate high-resolution, high-contrast images with a
      good depiction of anatomic and pathologic changes. However, shifting areas of
      signal dropout from the femoral heads to the center of the pelvis makes these
      areas not assessable. For clinical workflow CP2+ mode is most practical. Seven
      Tesla MRI of the hip joints may become a valuable complement to clinical field
      strengths.

PMID- 23955580
TI  - The impact of type 2 diabetes on numeric pain score reduction following cervical
      transforaminal epidural steroid injections.
AB  - OBJECTIVE: This study aimed to determine whether the presence of type 2 diabetes
      impairs the therapeutic response to transforaminal cervical epidural steroid
      injections (TF-CESI) in the treatment of pain due to cervical radiculopathy.
      DESIGN: This is a retrospective cohort study of patients with cervical
      radiculopathy who underwent TF-CESI performed by a single physician. SETTING:
      Single community-based multidisciplinary pain clinic and ambulatory surgery
      center. INTERVENTIONS: Patients underwent from one to three TF-CESI with
      dexamethasone or triamcinolone. MAIN OUTCOME MEASURES: Change in self-reported
      numerical pain score. RESULTS: Out of 387 charts reviewed, complete data were
      available for 329 subjects who underwent TF-CESI from February 2006 through
      January 2010. The injections consisted of either 40 mg triamcinolone or 15 mg
      dexamethasone. Of the 329 total subjects, 35 had type 2 diabetes and 294 did not.
      The diabetic group had a mean age of 58.1 years with standard deviation (SD) of
      11.2, mean body mass index (BMI) of 33.1 (SD 7.1), mean pre-procedure pain score
      of 6.7 (SD 2.2) and mean reduction in pain score of 2.5 (SD 2.4). The non
      diabetic group had a mean age of 52.8 (SD 12.4), mean BMI of 28.2 (SD 5.4), mean
      pre-procedure pain score of 6.7 (SD 1.8), and mean reduction in pain score of 2.4
      (SD 2.2). A two-sample t test with equivalent variance showed no statistically
      significant difference in the mean reduction in pain score between the diabetic
      and non-diabetic groups. The patients in the diabetic group were typically older
      and had higher BMIs. CONCLUSIONS: The efficacy of TF-CESI for treating cervical
      radicular pain in this set of 329 patients was independent of the presence of
      type 2 diabetes.

PMID- 23955581
TI  - Anterior cruciate ligament bundle measurement by MRI.
AB  - OBJECTIVE: An accurate in vivo method of measuring dimensions of the anteromedial
      (AM) and posterolateral (PL) anterior cruciate ligament (ACL) bundles has not
      been established. The purpose of this study was to measure each individual bundle
      using double oblique axial MR imaging of the ACL, to compare this with cadaveric
      measurements, and to investigate the range of measurements seen in normal
      subjects. MATERIALS AND METHODS: In five cadaveric knees, measurements obtained
      of the proximal, middle, and distal segments of each ACL bundle from double
      oblique axial MR images were compared with direct measurements following
      anatomical dissection. Thereafter, the size of both bundles from 24 normal knees
      was measured using an identical MR technique. Inter-observer variation was
      calculated using intraclass correlation. RESULTS: ACL bundle measurement in the
      cadaveric knees had a strong correlation (r = 0.93) with measurements obtained
      following anatomical dissection. No significant difference existed between
      measurements obtained from cadaveric knees and living normal subjects (p > 0.05).
      Interobserver correlation for MR measurements was excellent (R = 0.92-0.93).
      Overall, the long and short axis of the AM bundle were significantly larger than
      those of the PL bundle (p < 0.05). Also, men showed significantly larger AM and
      PL bundles than women (p < 0.05). Bundle size was not related to age or knee
      dominance. CONCLUSION: The individual ACL bundles can be accurately measured on
      double oblique axial MR imaging. The AM bundle is larger in caliber than the PL
      bundle. Both bundles are larger in men than in women and there is no significant
      side-to side difference.

PMID- 23955582
TI  - Women's experiences of doing long-term pelvic floor muscle exercises for the
      treatment of pelvic organ prolapse symptoms.
AB  - INTRODUCTION AND HYPOTHESIS: This study investigated women's experiences of doing
      prescribed pelvic floor muscle exercise (PFME) after participation in the Pelvic
      Organ Prolapse Physiotherapy (POPPY) trial. The aim was to understand post
      supervised treatment adherence to PFME and to inform future advice for women
      being treated for pelvic organ prolapse (POP). METHODS: Five women were
      purposively selected from the New Zealand branch of the multi-centre, multi
      national POPPY trial and took part in a semi-structured interviews about their
      experiences of PFME. The interviews were subjected to an interpretative
      phenomenological analysis (IPA). RESULTS: Three core themes were identified in
      the analysis. The first theme, "Patterns of PFME behaviour", described exercise
      characteristics and behaviours. The second theme, "Influences on PFME maintenance
      cycles", captured the participants' responses to and evaluations of their
      exercise practice and related PFME self-efficacy. The "cycle" referred to the
      changing influences on exercise behaviour. The third theme, "Family as priority",
      was expressed in terms of either putting family first or successfully combining
      the priorities of family and self. CONCLUSION: This study revealed the importance
      of family in influencing PFME patterns and behaviours in the treatment of POP. It
      is possible that identifying strategies to help women reach their PFME goals
      within the context of their families will promote more successful PFME adherence.
      The importance of family when prescribing exercise for women with other chronic
      health conditions is also worth exploring.

PMID- 23955583
TI  - Neuronal endoplasmic reticulum stress in axon injury and neurodegeneration.
AB  - Injuries to central nervous system axons result not only in Wallerian
      degeneration of the axon distal to the injury, but also in death or atrophy of
      the axotomized neurons, depending on injury location and neuron type. No method
      of permanently avoiding these changes has been found, despite extensive knowledge
      concerning mechanisms of secondary neuronal injury. The autonomous endoplasmic
      reticulum (ER) stress pathway in neurons has recently been implicated in
      retrograde neuronal degeneration. In addition to the emerging role of ER
      morphology in axon maintenance, we propose that ER stress is a common neuronal
      response to disturbances in axon integrity and a general mechanism for
      neurodegeneration. Thus, manipulation of the ER stress pathway could have
      important therapeutic implications for neuroprotection.

PMID- 23955584
TI  - Preoperative consolidation-to-tumor ratio and SUVmax stratify the risk of
      recurrence in patients undergoing limited resection for lung adenocarcinoma <=2
      cm.
AB  - PURPOSE: Limited resection is an increasingly utilized option for treatment of
      clinical stage IA lung adenocarcinoma (ADC) <=2 cm (T1aN0M0), yet there are no
      validated predictive factors for postoperative recurrence. We investigated the
      prognostic value of preoperative consolidation/tumor (C/T) ratio [on computed
      tomography (CT) scan] and maximum standardized uptake value (SUVmax) on (18)F
      fluorodeoxyglucose-positron emission tomography (PET) scan. METHODS: We
      retrospectively reviewed 962 consecutive patients who underwent limited resection
      for lung cancer at Memorial Sloan-Kettering between 2000 and 2008. Patients with
      available CT and PET scans were included in the analysis. C/T ratio of 25 % (in
      accordance with the Japan Clinical Oncology Group 0201) and SUVmax of 2.2 (cohort
      median) were used as cutoffs. Cumulative incidence of recurrence (CIR) was
      assessed. RESULTS: A total of 181 patients met the study inclusion criteria.
      Patients with a low C/T ratio (n = 15) had a significantly lower 5-year
      recurrence rate compared with patients with a high C/T ratio (n = 166) (5-year
      CIR, 0 vs. 33 %; p = 0.015), as did patients with low SUVmax (n = 86) compared
      with patients with high SUVmax (n = 95; 5-year CIR, 18 vs. 40 %; p = 0.002).
      Furthermore, within the high C/T ratio group, SUVmax further stratified risk of
      recurrence [5-year CIR, 22 % (low) vs. 40 % (high); p = 0.018]. CONCLUSIONS: With
      the expected increase in diagnoses of small lung ADC as a result of more
      widespread use of CT screening, C/T ratio and SUVmax are widely available markers
      that can be used to stratify the risk of recurrence among cT1aN0M0 patients after
      limited resection.

PMID- 23955585
TI  - A randomized phase II trial of three intensified chemotherapy regimens in first
      line treatment of colorectal cancer patients with initially unresectable or not
      optimally resectable liver metastases. The METHEP trial.
AB  - PURPOSE: This study was designed to evaluate neoadjuvant intensified chemotherapy
      in potentially resectable or unresectable liver metastases (LM) from colorectal
      cancer (CRC). METHODS: Criteria for potentially resectable LM were complex
      hepatectomy and/or risky procedure, close contact with major vascular structures,
      and for unresectable LM, a future liver remnant predicted to be less than 25-30 %
      of total liver volume. Between October 2004 and August 2007, 125 patients were
      randomized to either standard (FOLFIRI/FOLFOX4) or intensified chemotherapy
      (FOLFIRI-HD/FOLFOX7/FOLFIRINOX). Primary endpoint was objective response rate
      (ORR) after 4 cycles of chemotherapy. Secondary endpoints included safety, R0
      surgical resection, best ORR, progression-free survival (PFS), and overall
      survival (OS). RESULTS: A total of 122 patients were treated; 45 % of patients
      had less than 30 % of remaining liver tissue, 20 % had major vascular contact,
      and 35 % were potentially resectable. Grade 3/4 toxicities were neutropenia (24,
      19, 10, 23 %) diarrhoea (0, 6, 3, 23 %), mucositis (0, 3, 0, 7 %), vomiting (7,
      9, 0, 3 %), and neurotoxicity (0, 0, 10, 3 %) in arms (FOLFIRI + FOLFOX4)/FOLFIRI
      HD/FOLFOX7/FOLFIRINOX, respectively. ORR was 33, 47, 43, and 57 % after the first
      4 cycles in arms (FOLFIRI + FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively.
      FOLFIRINOX offered the best conversion rate to resectability (67 %). Disease-free
      status after chemotherapy and surgery (R0, R1, Rx) was achieved in 54 of 64
      operated patients. Median PFS was 9.2 months in control arms versus 11.9 months
      in experimental arms (hazards ratio [HR] = 0.76, p = 0.115), and the median OS
      was 17.7 versus 33.4 months (HR = 0.73, p = 0.297), respectively. CONCLUSIONS:
      FOLFIRINOX showed promising activity in CRC patients with LM compared with
      standard or intensified bi-chemotherapy regimens.

PMID- 23955586
TI  - Electronic structure trends in N-heterocyclic carbenes (NHCs) with varying number
      of nitrogen atoms and NHC-transition-metal bond properties.
AB  - Carbenes derived from five-membered heterocycles with different numbers of
      nitrogen atoms ranging from two to four lead formally either to normal N
      heterocyclic or mesoionic carbenes with, in some cases, the same skeletal
      structure. The electronic structures of fourteen of these compounds were examined
      by means of DFT calculations at the B3LYP/aug-cc-pVTZ level. The examined
      parameters include the energies of the sigma-lone pair at Ccarbene and the pi
      HOMO of the protonated form, which are correlated to the first and second proton
      affinities. The singlet-triplet energy gap was used as a measure of the stability
      of the N-heterocyclic carbene (NHC) towards dimerisation. Natural population
      analysis provided insight into the variation of the ppi population and the
      natural charge at Ccarbene with NHC structure. Additionally, the transition
      metal?NHC bond in L-AuCl and L-TiCl4 and the nature of the orbital interactions
      between the NHC and the transition-metal fragment were analysed in detail by the
      extended transition state-natural orbitals for chemical valence (ETS-NOCV)
      approach at the BP86/TZ2P level. Similarities and differences between the
      NHC?gold and the NHC?titanium bond are discussed, and trends in key bonding
      properties can be traced back to the variation of the electronic parameters of
      the NHC. 

PMID- 23955587
TI  - Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell
      infiltration into multiple organs and improves survival period for ATL model
      mice.
AB  - In the peripheral blood leukocytes (PBLs) from the carriers of the human T
      lymphotropic virus type-1 (HTLV-1) or the patients with adult T-cell leukemia
      (ATL), nuclear factor kappaB (NF-kappaB)-mediated antiapoptotic signals are
      constitutively activated primarily by the HTLV-1-encoded oncoprotein Tax. Tax
      interacts with the I kappaB kinase regulatory subunit NEMO (NF-kappaB essential
      modulator) to activate NF-kappaB, and this interaction is maintained in part by a
      molecular chaperone, heat-shock protein 90 (HSP90), and its co-chaperone cell
      division cycle 37 (CDC37). The antibiotic geldanamycin (GA) inhibits HSP90's ATP
      binding for its proper interaction with client proteins. Administration of a
      novel water-soluble and less toxic GA derivative, 17-dimethylaminoethylamino-17
      demethoxygeldanamycin hydrochloride (17-DMAG), to Tax-expressing ATL-transformed
      cell lines, C8166 and MT4, induced significant degradation of Tax. 17-DMAG also
      facilitated growth arrest and cellular apoptosis to C8166 and MT4 and other ATL
      cell lines, although this treatment has no apparent effects on normal PBLs. 17
      DMAG also downregulated Tax-mediated intracellular signals including the
      activation of NF-kappaB, activator protein 1 or HTLV-1 long terminal repeat in
      Tax-transfected HEK293 cells. Oral administration of 17-DMAG to ATL model mice
      xenografted with lymphomatous transgenic Lck-Tax (Lck proximal promoter-driven
      Tax transgene) cells or HTLV-1-producing tumor cells dramatically attenuated
      aggressive infiltration into multiple organs, inhibited de novo viral production
      and improved survival period. These observations identified 17-DMAG as a
      promising candidate for the prevention of ATL progression. 

PMID- 23955588
TI  - Prognostic significance of monitoring leukemia-associated immunophenotypes by
      eight-color flow cytometry in adult B-acute lymphoblastic leukemia.
AB  - Minimal residual disease (MRD) is of the most important factor for predicting
      prognosis and guiding treatment of acute lymphoblastic leukemia (ALL). In this
      study, we investigated the prognostic significance of leukemia-associated
      immunophenotypes (LAIPs) as assessment of index of MRD in 125 adult B-lineage ALL
      (B-ALL) patients by eight-color flow cytometry. The LAIPs could be identified in
      96% and 81.6% of patients with the sensitivity of 10(-4) and 10(-5),
      respectively. MRD-negative status could clearly predict a favorable 2-year
      relapse-free survival (RFS) and overall survival (OS) at the end of induction of
      complete remission and one cycle of consolidation treatment. Moreover, we
      identified a group of cases with MRD of 0.001% to <0.01%, which showed
      significantly higher 2-year relapse rate than those with undetectable one. In
      multivariate analysis, MRD status was associated with RFS or OS independently.
      Furthermore, MRD assessed by LAIPs and RQ-PCR assay for patients with BCR-ABL
      fusion gene yielded concordant results in 89.7% of cases. In conclusion, MRD
      evaluated by eight-color flow cytometry could provide an important tool to assess
      treatment response and prognosis precisely in adult B-ALL. 

PMID- 23955589
TI  - A single-tube multiparameter seven-colour flow cytometry strategy for the
      detection of malignant plasma cells in multiple myeloma.

PMID- 23955590
TI  - Loss of the xeroderma pigmentosum group B protein binding site impairs p210
      BCR/ABL1 leukemogenic activity.
AB  - Previous studies have demonstrated that p210 BCR/ABL1 interacts directly with the
      xeroderma pigmentosum group B (XPB) protein, and that XPB is phosphorylated on
      tyrosine in cells that express p210 BCR/ABL1. In the current study, we have
      constructed a p210 BCR/ABL1 mutant that can no longer bind to XPB. The mutant has
      normal kinase activity and interacts with GRB2, but can no longer phosphorylate
      XPB. Loss of XPB binding is associated with reduced expression of c-MYC and
      reduced transforming potential in ex-vivo clonogenicity assays, but does not
      affect nucleotide excision repair in lymphoid or myeloid cells. When examined in
      a bone marrow transplantation (BMT) model for chronic myelogenous leukemia, mice
      that express the mutant exhibit attenuated myeloproliferation and
      lymphoproliferation when compared with mice that express unmodified p210
      BCR/ABL1. Thus, the mutant-transplanted mice show predominantly neutrophilic
      expansion and altered progenitor expansion, and have significantly extended
      lifespans. This was confirmed in a BMT model for B-cell acute lymphoblastic
      leukemia, wherein the majority of the mutant-transplanted mice remain disease
      free. These results suggest that the interaction between p210 BCR/ABL1 and XPB
      can contribute to disease progression by influencing the lineage commitment of
      lymphoid and myeloid progenitors. 

PMID- 23955591
TI  - Salivary levels of mutans streptococci and Lactobacilli among Palestinian school
      children in East Jerusalem.
AB  - OBJECTIVES: The aim of the present study was to investigate the distribution of
      oral cariogenic bacteria among 12-year-old Palestinian children attending schools
      in East Jerusalem. MATERIALS AND METHODS: Salivary levels of mutans streptococci
      (MS) and Lactobacilli (LB) were examined by semi-quantitative commercial kits and
      then correlated to social-demographic parameters. RESULTS: Overall, 52.1 % of the
      examined children presented the highest possible ranking score categories for MS
      bacteria, with only 5.4 % in the lowest category. Only 12.6 % of the school
      children presented the highest LB score, while 25 % had the lowest ranking score.
      Salivary MS levels in children attending private schools were lower than those of
      children in government schools and United Nations Relief and Works Agency (UNRWA)
      schools. Conversely, levels of LB were lowest in children attending UNRWA schools
      compared to government and private schools. Girls had significantly higher
      amounts of MS and LB than boys (p = 0.001). Lower MS levels were significantly
      related to the following socioeconomic variables: higher father's education level
      (p = 0.037), higher mother's education level (p = 0.063), mother's employment
      status (p = 0.012), and lower home density (p = 0.001). For LB, the only
      significant socioeconomic variable was higher father's employment level, which
      was related to lower LB level (p = 0.025). CONCLUSIONS: Levels of MS and LB were
      found to be strongly related with socioeconomic status among Palestinian children
      in East Jerusalem. The relatively high prevalence of cariogenic bacteria suggests
      that oral care prevention and treatment demands special attention from the health
      care institutions and authorities.

PMID- 23955593
TI  - Where does the new regime of medical specialty certification go?
AB  - The certification system of medical specialty is going to be changed to a new
      regime after the proposal of reorganization conducted by the Government in 2013.
      This review focuses on the issue of program-based accreditation of the training
      institution which is the core of the new regime. In particular, the strategy for
      surgical subspecialty such as thoracic surgery is discussed. 

PMID- 23955592
TI  - Differential recognition of syk-binding sites by each of the two phosphotyrosine
      binding pockets of the Vav SH2 domain.
AB  - The association of spleen tyrosine kinase (Syk), a central tyrosine kinase in B
      cell signaling, with Vav SH2 domain is controlled by phosphorylation of two
      closely spaced tyrosines in Syk linker B: Y342 and Y346. Previous studies
      established both singly phosphorylated and doubly phosphorylated forms play a
      role in signaling. The structure of the doubly phosphorylated form identified a
      new recognition of phosphotyrosine whereby two phosphotyrosines bind
      simultaneously to the Vav SH2 domain, one in the canonical pTyr pocket and one in
      the specificity pocket on the opposite side of the central beta-sheet. It is
      unknown if the specificity pocket can bind phosphotyrosine independent of
      phosphotyrosine binding the pTyr pocket. To address this gap in knowledge, we
      determined the structure of the complex between Vav1 SH2 and a peptide (SykLB
      YpY) modeling the singly phosphorylated-Y346 form of Syk with unphosphorylated
      Y342. The nuclear magnetic resonance (NMR) data conclusively establish that
      recognition of phosphotyrosine is swapped between the two pockets; phosphorylated
      pY346 binds the specificity pocket of Vav1 SH2, and unphosphorylated Y342
      occupies what is normally the pTyr binding pocket. Nearly identical changes in
      chemical shifts occurred upon binding all three forms of singly and doubly
      phosphorylated peptides; however, somewhat smaller shift perturbations for SykLB
      YpY from residues in regions of high internal mobility suggest that internal
      motions are coupled to binding affinity. The differential recognition that
      includes this swapped binding of phosphotyrosine to the specificity pocket of Vav
      SH2 increases the repertoire of possible phosphotyrosine binding by SH2 domains
      in regulating protein-protein interactions in cellular signaling.

PMID- 23955594
TI  - Antennal sensilla of the green bottle fly, Lucilia sericata (Meigen) (Diptera:
      Calliphoridae).
AB  - Lucilia sericata (Meigen) is a cosmopolitan synanthropic fly of forensic and
      medical importance, which can work as a mechanic vector of pathogens or cause
      myiasis of both human and sheep. As essential olfactory organs, antennae of adult
      L. sericata were examined with stereoscopic microscope, scanning electron
      microscope, and laser scanning confocal microscope. On antennal scape and
      pedicel, both microtirchiae and several bristles are detected, while another two
      structures, setiferous plaques and pedicellar buttons, are also found on the
      antennal pedicel. Seven subtypes of antennal sensilla are observed on antennal
      funiculus including one subtype of trichoid sensilla, two subtypes of basiconic
      sensilla, two subtypes of coeloconic sensilla, and two subtypes of sensory pits.
      Size and density of the former four types of sensilla on antennal funiculus are
      measured. Three distinctive sensillar characters of L. sericata are detected,
      which may contribute to greater olfactory sensitivity of this species and their
      wide distribution throughout the world. Unlike the common poreless pedicellar
      button with mechanoreceptor function, every pedicellar button in L. sericata is
      perforated by three pores, which might indicate potential chemoreceptor function
      of this structure. Besides, another unique feature is greater number of
      setiferous plaques in genus Lucilia than calliphorids of other genera. Expect for
      the common sensory pits with basiconic or basiconic-like sensilla in them,
      sensory pits filled with rarely described coeloconic-like sensilla are founded in
      L. sericata as well. After comparison with previous equivalent findings, the
      functions of these specific structures are discussed according to the life
      history of this calliphorid.

PMID- 23955595
TI  - An in vivo mouse model of intraosseous spinal cancer causing evolving paraplegia.
AB  - The spine is the commonest site of skeletal metastatic disease and uncontrolled
      growth of cancer in the spine will inevitably cause pain and neurologic
      compromise. Improved understanding of the pathobiology behind this devastating
      condition is urgently needed. For this reason, the aim of this study was to
      establish a clinically relevant, animal model of spinal cancer. A percutaneous
      orthotopic injection of human breast (MDA-MB-231) or human prostate (PC-3) cancer
      cells was administered into the upper lumbar spine of nude mice (n = 6). Animals
      were monitored twice daily for general welfare, gait asymmetry or disturbance,
      and hindlimb weakness. After sacrifice, plain radiographs, micro-CT imaging and
      histological analysis of the spines were performed on each mouse. All mice
      recovered fully from the inoculation procedure and displayed normal gait and
      behaviour patterns for at least 3 weeks post-inoculation. Subsequently, between 3
      and 5 weeks post-inoculation, each mouse developed evolving paralysis in their
      hindlimbs over 48-72 h. All followed the same pattern of decline following onset
      of neurological dysfunction; from gait asymmetry and unilateral hindlimb
      weakness, to complete unilateral hindlimb paralysis and finally to complete
      bilateral hindlimb paralysis. Plain radiographs, micro-CT scanning and
      histological analysis confirmed local tumour growth and destruction of the spine
      in all six mice. An in vivo mouse model of human intraosseous spinal cancer has
      been established forming cancers that grow within the spine and cause epidural
      spinal cord compression, resulting in a reproducible, evolving neurological
      deficit and paralysis that closely resembles the human condition.

PMID- 23955596
TI  - Variants in CPA1 are strongly associated with early onset chronic pancreatitis.
AB  - Chronic pancreatitis is an inflammatory disorder of the pancreas. We analyzed
      CPA1, encoding carboxypeptidase A1, in subjects with nonalcoholic chronic
      pancreatitis (cases) and controls in a German discovery set and three replication
      sets. Functionally impaired variants were present in 29/944 (3.1%) German cases
      and 5/3,938 (0.1%) controls (odds ratio (OR) = 24.9, P = 1.5 * 10(-16)). The
      association was strongest in subjects aged <= 10 years (9.7%; OR = 84.0, P = 4.1
      * 10(-24)). In the replication sets, defective CPA1 variants were present in
      8/600 (1.3%) cases and 9/2,432 (0.4%) controls from Europe (P = 0.01), 5/230
      (2.2%) cases and 0/264 controls from India (P = 0.02) and 5/247 (2.0%) cases and
      0/341 controls from Japan (P = 0.013). The mechanism by which CPA1 variants
      confer increased pancreatitis risk may involve misfolding-induced endoplasmic
      reticulum stress rather than elevated trypsin activity, as is seen with other
      genetic risk factors for this disease.

PMID- 23955598
TI  - Mapping the fine structure of a eukaryotic promoter input-output function.
AB  - The precise tuning of gene expression levels is essential for the optimal
      performance of transcriptional regulatory networks. We created 209 variants of
      the Saccharomyces cerevisiae PHO5 promoter to quantify how different binding
      sites for the transcription factor Pho4 affect its output. We found that
      transcription-factor binding affinities determined in vitro could quantitatively
      predict the output of a complex yeast promoter. Promoter output was precisely
      tunable by subtle changes in binding-site affinity of less than 3 kcal mol(-1),
      which are accessible by modifying 1-2 bases. Our results provide insights into
      how transcription-factor binding sites regulate gene expression, their possible
      evolution and how they can be used to precisely tune gene expression. More
      generally, we show that in vitro binding-energy landscapes of transcription
      factors can precisely predict the output of a native yeast promoter, indicating
      that quantitative models of transcriptional regulatory networks are feasible. 

PMID- 23955597
TI  - Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple
      myeloma risk.
AB  - To identify variants for multiple myeloma risk, we conducted a genome-wide
      association study with validation in additional series totaling 4,692 individuals
      with multiple myeloma (cases) and 10,990 controls. We identified four risk loci
      at 3q26.2 (rs10936599, P = 8.70 * 10(-14)), 6p21.33 (rs2285803, PSORS1C2, P =
      9.67 * 10(-11)), 17p11.2 (rs4273077, TNFRSF13B, P = 7.67 * 10(-9)) and 22q13.1
      (rs877529, CBX7, P = 7.63 * 10(-16)). These data provide further evidence for
      genetic susceptibility to this B-cell hematological malignancy, as well as
      insight into the biological basis of predisposition. 

PMID- 23955599
TI  - Recurrent mutations in multiple components of the cohesin complex in myeloid
      neoplasms.
AB  - Cohesin is a multimeric protein complex that is involved in the cohesion of
      sister chromatids, post-replicative DNA repair and transcriptional regulation.
      Here we report recurrent mutations and deletions involving multiple components of
      the cohesin complex, including STAG2, RAD21, SMC1A and SMC3, in different myeloid
      neoplasms. These mutations and deletions were mostly mutually exclusive and
      occurred in 12.1% (19/157) of acute myeloid leukemia, 8.0% (18/224) of
      myelodysplastic syndromes, 10.2% (9/88) of chronic myelomonocytic leukemia, 6.3%
      (4/64) of chronic myelogenous leukemia and 1.3% (1/77) of classical
      myeloproliferative neoplasms. Cohesin-mutated leukemic cells showed reduced
      amounts of chromatin-bound cohesin components, suggesting a substantial loss of
      cohesin binding sites on chromatin. The growth of leukemic cell lines harboring a
      mutation in RAD21 (Kasumi-1 cells) or having severely reduced expression of RAD21
      and STAG2 (MOLM-13 cells) was suppressed by forced expression of wild-type RAD21
      and wild-type RAD21 and STAG2, respectively. These findings suggest a role for
      compromised cohesin functions in myeloid leukemogenesis. 

PMID- 23955600
TI  - Integrative genetic, epigenetic and pathological analysis of paraganglioma
      reveals complex dysregulation of NOTCH signaling.
AB  - Head and neck paragangliomas, rare neoplasms of the paraganglia composed of nests
      of neurosecretory and glial cells embedded in vascular stroma, provide a
      remarkable example of organoid tumor architecture. To identify genes and pathways
      commonly deregulated in head and neck paraganglioma, we integrated high-density
      genome-wide copy number variation (CNV) analysis with microRNA and
      immunomorphological studies. Gene-centric CNV analysis of 24 cases identified a
      list of 104 genes most significantly targeted by tumor-associated alterations.
      The "NOTCH signaling pathway" was the most significantly enriched term in the
      list (P = 0.002 after Bonferroni or Benjamini correction). Expression of the
      relevant NOTCH pathway proteins in sustentacular (glial), chief (neuroendocrine)
      and endothelial cells was confirmed by immunohistochemistry in 47 head and neck
      paraganglioma cases. There were no relationships between level and pattern of
      NOTCH1/JAG2 protein expression and germline mutation status in the SDH genes,
      implicated in paraganglioma predisposition, or the presence/absence of
      immunostaining for SDHB, a surrogate marker of SDH mutations. Interestingly,
      NOTCH upregulation was observed also in cases with no evidence of CNVs at NOTCH
      signaling genes, suggesting altered epigenetic modulation of this pathway. To
      address this issue we performed microarray-based microRNA expression analyses.
      Notably 5 microRNAs (miR-200a,b,c and miR-34b,c), including those most
      downregulated in the tumors, correlated to NOTCH signaling and directly targeted
      NOTCH1 in in vitro experiments using SH-SY5Y neuroblastoma cells. Furthermore,
      lentiviral transduction of miR-200s and miR-34s in patient-derived primary
      tympano-jugular paraganglioma cell cultures was associated with NOTCH1
      downregulation and increased levels of markers of cell toxicity and cell death.
      Taken together, our results provide an integrated view of common molecular
      alterations associated with head and neck paraganglioma and reveal an essential
      role of NOTCH pathway deregulation in this tumor type. 

PMID- 23955601
TI  - Amyloid and tau: neither chicken nor egg but two partners in crime!

PMID- 23955602
TI  - Impaired high-density lipoprotein anti-oxidant capacity in human abdominal aortic
      aneurysm.
AB  - AIMS: Abdominal aortic aneurysm (AAA) is a particular form of atherothrombotic
      disease characterized by the dilation of the aortic wall and the presence of an
      intraluminal thrombus (ILT). The objective of the present study was to evaluate
      the pro-oxidant properties of the ILT and to characterize the anti-oxidant
      capacity of high-density lipoproteins (HDLs). METHODS AND RESULTS: Our results
      show that ILT, adventitia, and plasma from AAA patients contained high
      concentrations of lipid and protein oxidation products. Mediators produced within
      or released by the thrombus and the adventitia were shown to induce reactive
      oxygen species (ROS) production by cultured aortic smooth muscle cells (AoSMCs)
      and to trigger the onset of apoptosis (an increase in mitochondrial membrane
      potential). Iron chelation limited these effects. Both concentration and
      functionality of HDLs were altered in AAA patients. Plasma levels of Apo A-I were
      lower, and small HDL subclasses were decreased in AAA patients. Circulating HDLs
      in AAA patients displayed an impaired capacity to inhibit copper-induced low
      density lipoprotein oxidation and AoSMC ROS production. Western blot analyses of
      HDLs demonstrated that myeloperoxidase is associated with HDL particles in AAA
      patients. CONCLUSION: ILT and adventitia are a source of pro-oxidant products, in
      particular haemoglobin, which may impact on the wall stability/rupture in AAA. In
      addition, HDLs from AAA patients exhibit an impaired anti-oxidant activity. In
      this context, restoring HDL functionality may represent a new therapeutic option
      in AAA.

PMID- 23955603
TI  - Is there a minimum intensity threshold for resistance training-induced
      hypertrophic adaptations?
AB  - In humans, regimented resistance training has been shown to promote substantial
      increases in skeletal muscle mass. With respect to traditional resistance
      training methods, the prevailing opinion is that an intensity of greater than ~60
      % of 1 repetition maximum (RM) is necessary to elicit significant increases in
      muscular size. It has been surmised that this is the minimum threshold required
      to activate the complete spectrum of fiber types, particularly those associated
      with the largest motor units. There is emerging evidence, however, that low
      intensity resistance training performed with blood flow restriction (BFR) can
      promote marked increases in muscle hypertrophy, in many cases equal to that of
      traditional high-intensity exercise. The anabolic effects of such occlusion-based
      training have been attributed to increased levels of metabolic stress that
      mediate hypertrophy at least in part by enhancing recruitment of high-threshold
      motor units. Recently, several researchers have put forth the theory that low
      intensity exercise (<=50 % 1RM) performed without BFR can promote increases in
      muscle size equal, or perhaps even superior, to that at higher intensities,
      provided training is carried out to volitional muscular failure. Proponents of
      the theory postulate that fatiguing contractions at light loads is simply a
      milder form of BFR and thus ultimately results in maximal muscle fiber
      recruitment. Current research indicates that low-load exercise can indeed promote
      increases in muscle growth in untrained subjects, and that these gains may be
      functionally, metabolically, and/or aesthetically meaningful. However, whether
      hypertrophic adaptations can equal that achieved with higher intensity resistance
      exercise (<=60 % 1RM) remains to be determined. Furthermore, it is not clear as
      to what, if any, hypertrophic effects are seen with low-intensity exercise in
      well-trained subjects as experimental studies on the topic in this population are
      lacking. Practical implications of these findings are discussed. 

PMID- 23955604
TI  - An observational cohort study of the effect of hypertension on the loss of renal
      function in pediatric kidney recipients.
AB  - BACKGROUND: Post-transplant hypertension impacts negatively on renal graft
      survival. Our primary objective was to analyze the effect of hypertension on the
      glomerular filtration rate (GFR) slope. METHODS: All clinical charts of children
      who underwent renal transplantation since the introduction of the routine use of
      ambulatory blood pressure monitoring (ABPM) were reviewed. Eligibility criteria
      for inclusion were measurement of GFR at 3 months, at 1 year post-transplant, and
      thereafter at yearly intervals; ABPM performed annually after transplantation;
      and functioning graft for a minimum of 2 years. RESULTS: Sixty-eight (39 males)
      of 79 patients, aged 9.1+/-5.3 years, met the inclusion criteria. The mean follow
      up was 6.2+/-2.8 years. Twenty-four patients had normotension or controlled
      hypertension throughout their follow-up (normotensive group). Forty-four patients
      had hypertension or noncontrolled hypertension at some point(s) during the follow
      up period (hypertensive group). GFR slope was -1.6ml/min/1.73 m(2) per year (95%
      confidence interval (CI = -3.7 to 0.4) in the normotensive group and 
      2ml/min/1.73 m(2) per year (95% CI = -3 to -1.1) in the hypertensive group (P =
      0.42). There was no difference between groups with regard to the change in GFR
      values from 3 months to 1 year and to last control (P = 0.87). At most recent
      control, the overall prevalence of controlled hypertension was 78.2% (95% CI =
      63.6-89.1). CONCLUSIONS: Although the results of our study are encouraging, they
      need to be confirmed in a larger prospective study using the same post-transplant
      follow-up protocol.

PMID- 23955605
TI  - How many measurements are needed to estimate blood pressure variability without
      loss of prognostic information?
AB  - BACKGROUND: Average real variability (ARV) is a recently proposed index for short
      term blood pressure (BP) variability. We aimed to determine the minimum number of
      BP readings required to compute ARV without loss of prognostic information.
      METHODS: ARV was calculated from a discovery dataset that included 24-hour
      ambulatory BP measurements for 1,254 residents (mean age = 56.6 years; 43.5%
      women) of Copenhagen, Denmark. Concordance between ARV from full (>=80 BP
      readings) and randomly reduced 24-hour BP recordings was examined, as was
      prognostic accuracy. A test dataset that included 5,353 subjects (mean age = 54.0
      years; 45.6% women) with at least 48 BP measurements from 11 randomly recruited
      population cohorts was used to validate the results. RESULTS: In the discovery
      dataset, a minimum of 48 BP readings allowed an accurate assessment of the
      association between cardiovascular risk and ARV. In the test dataset, over 10.2
      years (median), 806 participants died (335 cardiovascular deaths, 206 cardiac
      deaths) and 696 experienced a major fatal or nonfatal cardiovascular event.
      Standardized multivariable-adjusted hazard ratios (HRs) were computed for
      associations between outcome and BP variability. Higher diastolic ARV in 24-hour
      ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular
      (HR = 1.19), and cardiac (HR = 1.19) mortality and fatal combined with nonfatal
      cerebrovascular events (HR = 1.16). Higher systolic ARV in 24-hour ambulatory BP
      recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.17),
      and cardiac (HR = 1.24) mortality. CONCLUSIONS: Forty-eight BP readings over 24
      hours were observed to be adequate to compute ARV without meaningful loss of
      prognostic information.

PMID- 23955606
TI  - Euglycemic hyperinsulinemia increases blood pressure in pregnant rats independent
      of placental antiangiogenic and inflammatory factors.
AB  - BACKGROUND: Although pregnancies associated with hyperinsulinemia and altered
      placental angiogenic and inflammatory factors are at increased risk for
      developing preeclampsia, the effects of euglycemic hyperinsulinemia on placental
      factors and blood pressure regulation during pregnancy are unclear. We
      hypothesized that chronic hyperinsulinemia results in increased placental soluble
      fms-like tyrosine kinase 1(sFlt-1) and tumor necrosis factor alpha (TNF- alpha)
      levels and hypertension in pregnant rats. METHODS: On gestational day (GD) 14,
      Sprague-Dawley rats were assigned as normal pregnant or pregnant + insulin.
      Insulin was infused subcutaneously by osmotic minipump for 5 days at a dose of
      1.5 mU/kg/min. Those rats receiving insulin were supplemented with 20% glucose in
      drinking water to maintain euglycemia. On GD 19, mean arterial pressure (MAP) and
      heart rate (HR) were assessed in conscious rats by indwelling carotid catheters,
      followed by collections of blood, placentas, and fetuses. In addition to
      placental sFlt-1 and TNF-alpha levels, circulating insulin, glucose, leptin,
      cholesterol, triglyceride, and free fatty acid concentrations were measured.
      RESULTS: MAP was higher in pregnant + insulin vs. normal pregnant rats; however,
      HR was similar between groups. Although litter size and placental weight were
      comparable, fetuses from pregnant + insulin rats were heavier. Importantly,
      circulating insulin concentration was elevated in the pregnant + insulin group,
      with no change in glucose level. Moreover, circulating leptin, cholesterol,
      triglyceride, and free fatty acid concentrations were increased in the pregnant +
      insulin group. There were no differences in placental sFlt-1 and TNF-alpha
      concentrations between groups. CONCLUSIONS: In summary, sustained euglycemic
      hyperinsulinemia, comparable with insulin levels in preeclamptic women, can raise
      blood pressure in pregnancy independent of recognized placental factors
      associated with preeclampsia.

PMID- 23955607
TI  - Health and access to care for undocumented migrants living in the European Union:
      a scoping review.
AB  - BACKGROUND: Literature on health and access to care of undocumented migrants in
      the European Union (EU) is limited and heterogeneous in focus and quality.
      Authors conducted a scoping review to identify the extent, nature and
      distribution of existing primary research (1990-2012), thus clarifying what is
      known, key gaps, and potential next steps. METHODS: Authors used Arksey and
      O'Malley's six-stage scoping framework, with Levac, Colquhoun and O'Brien's
      revisions, to review identified sources. Findings were summarized thematically:
      (i) physical, mental and social health issues, (ii) access and barriers to care,
      (iii) vulnerable groups and (iv) policy and rights. RESULTS: Fifty-four sources
      were included of 598 identified, with 93% (50/54) published during 2005-2012. EU
      member states from Eastern Europe were under-represented, particularly in single
      country studies. Most study designs (52%) were qualitative. Sampling descriptions
      were generally poor, and sampling purposeful, with only four studies using any
      randomization. Demographic descriptions were far from uniform and only two
      studies focused on undocumented children and youth. Most (80%) included findings
      on health-care access, with obstacles reported at primary, secondary and tertiary
      levels. Major access barriers included fear, lack of awareness of rights,
      socioeconomics. Mental disorders appeared widespread, while obstetric needs and
      injuries were key reasons for seeking care. Pregnant women, children and
      detainees appeared most vulnerable. While EU policy supports health-care access
      for undocumented migrants, practices remain haphazard, with studies reporting
      differing interpretation and implementation of rights at regional, institutional
      and individual levels. CONCLUSIONS: This scoping review is an initial attempt to
      describe available primary evidence on health and access to care for undocumented
      migrants in the European Union. It underlines the need for more and better
      quality research, increased co-operation between gatekeepers, providers,
      researchers and policy makers, and reduced ambiguities in health-care rights and
      obligations for undocumented migrants.

PMID- 23955608
TI  - The size, characteristics and partnership networks of the health-related non
      profit sector in three regions of South Africa: implications of changing primary
      health care policy for community-based care.
AB  - BACKGROUND: Health-related community-based care in South Africa is mostly
      provided through non-profit organizations (NPOs), but little is known about the
      sector. In the light of emerging government policy on greater formalization of
      community-based care in South Africa, this article assesses the size,
      characteristics and partnership networks of health-related NPOs in three South
      African communities and explores implications of changing primary health care
      policy for this sector. METHODS: Data were collected (2009-11) from three sites:
      Khayelitsha (urban), Botshabelo (semi-rural) and Bushbuckridge (semi/deep rural).
      Separate data sources were used to identify all health-related NPOs in the sites.
      Key characteristics of identified NPOs were gathered using a standardized tool. A
      typology of NPOs was developed combining level of resources (well, moderate,
      poor) and orientation of activities ('Direct service', 'Developmental' and/or
      'Activist'). Network analysis was performed to establish degree and density of
      partnerships among NPOs. RESULTS: The 138 NPOs (n = 56 in Khayelitsha, n = 47 in
      Bushbuckridge; n = 35 in Botshabelo) were mostly local community-based
      organizations (CBOs). The main NPO orientation was 'Direct service' (n = 120,
      87%). Well- and moderately resourced NPOs were successful at combining
      orientations. Most organizations with an 'Activist' orientation were urban. No
      poorly resourced organizations had this orientation. Well-resourced organizations
      with an 'Activist' orientation were highly connected in Khayelitsha NPO networks,
      while poorly resourced CBOs were marginalized. A contrasting picture emerged in
      Botshabelo where CBOs were highly connected. Networks in Bushbuckridge were
      fragmented and linear. CONCLUSIONS: The NPO sector varies geographically in
      numbers, resources, orientation of activities and partnership networks. NPOs may
      perform important developmental roles and strong potential for social capital may
      reside in organizational networks operating in otherwise impoverished
      environments. A uniform approach to policy implementation may not accommodate
      variations in the NPO sector. Considerations for adaptation may be necessary in
      light of the observed differences between urban and rural settings.

PMID- 23955609
TI  - Prevalence of Howell-Jolly bodies caused by partial splenic embolization for
      portal hypertension.
AB  - OBJECTIVE: Postsplenectomy sepsis (PSS) and overwhelming postsplenectomy
      infection (OPSI) following splenectomy or the development of hyposplenism are
      associated with a high mortality rate. The presence of Howell-Jolly bodies (HJBs)
      in peripheral erythrocytes is attracting attention as a parameter of
      hyposplenism. To date, whether HJBs appear following partial splenic embolization
      (PSE) has not been investigated. Therefore, we examined the prevalence of HJBs in
      patients who have undergone PSE. METHODS: Whether HJBs were present in 95
      patients who underwent PSE between November 2007 and August 2012 was assessed.
      RESULTS: No serious complications occurred due to PSE; however, 17 of the 95
      patients (17.89%) exhibited HJBs during the follow-up. The residual spleen volume
      and splenic infarction rate did not differ significantly compared to those
      observed in the HJB-negative group. CONCLUSION: With the recent increase in the
      use of autoanalyzers, the opportunities to perform microscopic examinations have
      been decreasing. Therefore, the presence of HJBs, which can only be confirmed
      visually, may be overlooked, and the clinical significance of these bodies tends
      to be disregarded. However, the presence of HJBs is associated with a risk of PSS
      and OPSI due to hyposplenism. Because HJBs are common in the peripheral
      erythrocytes of patients who have undergone PSE, irrespective of the residual
      spleen volume or splenic infarction rate, the presence or absence of HJBs should
      be assessed visually. In HJB-positive patients, preventing serious infections,
      for example, by administering the pneumococcal vaccine, is important.

PMID- 23955610
TI  - Relationship between the red cell distribution width and the one-year outcomes in
      Chinese patients with stable angina pectoris.
AB  - OBJECTIVE: This study was undertaken to determine the relationship between the
      red cell distribution width (RDW) and the one year outcomes in Chinese patients
      with stable angina pectoris. METHODS: A total of 1,442 patients with stable
      angina pectoris on admission were divided into four groups according to quartiles
      of the baseline RDW. The relationships between the RDW and one-year cardiac
      mortality as well as the incidence of acute coronary syndrome (ACS) were
      assessed. RESULTS: Higher RDW values were associated with an increased one-year
      cardiac mortality (quartile 1: 0.51%; quartile 2: 0.56%; quartile 3: 0.86%;
      quartile 4: 2.27%; p<0.001) and one-year ACS (quartile 1: 1.55%; quartile 2:
      1.96%; quartile 3: 2.89%; quartile 4: 3.70%; p<0.001). A logistic regression
      analysis revealed that the RDW independently predicted cardiac mortality (OR:
      1.544, 95% CI: 1.058-3.216, p<0.001) and ACS (OR: 1.861, 95% CI: 1.226-3.487,
      p<0.001) during a one-year follow-up in patients with stable angina pectoris.
      CONCLUSION: The present study indicates that an elevated RDW value is associated
      with an increased risk of one-year adverse outcomes in patients with stable
      angina pectoris.

PMID- 23955611
TI  - Relationships between the visceral fat area on CT and coronary risk factor
      markers.
AB  - OBJECTIVE: The visceral fat area (VFA) was measured, and the relationships
      between the VFA and the body mass index (BMI), waist circumference, blood
      pressure, and indices of lipid and sugar metabolism were evaluated. METHODS: The
      subjects included 607 consecutive patients who underwent VFA examinations using
      computed tomography (CT) scans. In addition to the routine examination
      parameters, the levels of adiponectin and homeostasis model assessment as an
      index of insulin resistance (HOMA-IR) were measured in all subjects, and the
      levels of malondialdehyde-modified low-density lipoprotein (MDA-LDL), remnant
      like particles (RLP), lipoprotein (a) (Lp(a)), apolipoprotein (Apo) AI, ApoB and
      ApoE were measured in 270 subjects. RESULTS: In both men and women, the VFA
      showed significant positive correlations with the age, BMI, waist circumference,
      subcutaneous fat area, visceral fat area/subcutaneous fat area (v/s) ratio,
      systolic blood pressure, diastolic blood pressure, the fasting blood sugar (FBS),
      the hemoglobin A1c (HbA1c), high-density lipoprotein cholesterol (HDLC),
      triglyceride (TG), uric acid, HOMA-IR and ApoB and the ApoB/LDLC ratio and
      significant negative correlations with the levels of HDLC and adiponectin. The
      levels of the total cholesterol (TC), low-density lipoprotein cholesterol (LDLC),
      non-HDLC, MDA-LDL and Lp(a) and the ApoB/ApoAI ratio were not correlated with the
      VFA in either men or women. The RLP exhibited a significant positive correlation
      with the VFA in women. CONCLUSION: The VFA exhibited high positive correlations
      with the waist circumference, blood pressure and TG level and a negative
      correlation with the HDLC level, regardless of gender, supporting the validity of
      the present diagnostic method for evaluating metabolic syndrome (MS). Although
      the LDLC level is not included in the diagnostic criteria for MS, the positive
      correlations between the VFA and the ApoB level and ApoB/LDLC ratio observed in
      both men and women indicate qualitative abnormalities of lipoproteins, such as an
      increase in the amount of small dense LDL. Measuring the levels of
      apolipoproteins in addition to lipoproteins during health screening is therefore
      useful for evaluating of atherogenicity.

PMID- 23955612
TI  - Predictors of the need to initiate noninvasive ventilation in stable outpatients
      with acute exacerbation of chronic obstructive pulmonary disease.
AB  - OBJECTIVE: Predictors of the need to initiate noninvasive ventilation (NIV) in
      stable COPD outpatients with acute exacerbation of chronic obstructive pulmonary
      disease (COPD-AE) are insufficiently defined. The objective of this study was to
      investigate predictors of the need to initiate NIV in stable COPD-AE outpatients.
      METHODS: A total of 140 consecutive stable COPD outpatients who were hospitalized
      for COPD-AE for the first time were retrospectively examined. Demographic and
      clinical parameters measured in the stable state were evaluated, including data
      for arterial blood gases, the pulmonary function, body mass index and dyspnea
      scores. RESULTS: Of the 140 patients included, NIV was used in 32 (23%) patients.
      In a univariate Cox proportional hazards analysis, the baseline partial pressure
      of arterial carbon dioxide (PaCO2) (hazard ratio (HR), 1.14 per mmHg; 95%
      confidence interval (CI), 1.08-1.21) and forced expiratory volume in one second
      (FEV1)% predicted (HR, 1.03 per %; 95% CI, 1.01-1.05) were identified to be
      significant predictors. A multivariate logistic regression analysis showed only
      the PaCO2 (HR, 1.18 per mmHg; 95% CI, 1.12-1.26) to be a significant predictor.
      CONCLUSION: Our results suggest that the PaCO2 measured in the stable state is an
      independent significant predictor of the need to initiate NIV in COPD-AE patients
      who are hospitalized for the first time.

PMID- 23955613
TI  - Is neuroinflammation involved in the development of dementia in patients with
      Parkinson's disease?
AB  - OBJECTIVE: High-sensitivity C-reactive protein (hs-CRP) is an extremely sensitive
      systemic marker of inflammation and tissue damage, and increased levels of hs-CRP
      are strongly associated with inflammatory reactions. Microglia-mediated
      neuroinflammation has been hypothesized to play an important role in the
      pathogenesis of idiopathic Parkinson's disease (PD). However, the clinical value
      of the hs-CRP level in patients with PD is poorly defined. Therefore, we
      conducted this study to analyze the differences in the hs-CRP levels in PD
      patients with and without dementia. METHODS: We examined 72 PD patients without
      dementia (PDwoD) and 45 PD patients with dementia (PDD), as well as 84 control
      subjects. We investigated the differences in the hs-CRP and fibrinogen levels
      between these three groups. RESULTS: The mean hs-CRP and fibrinogen values were
      not significantly different between the PDwoD and PDD groups; however, these two
      groups had significantly higher mean hs-CRP and fibrinogen values than the
      control group. CONCLUSION: It is known that inflammation plays a role in the
      pathogenesis of PD and dementia. However, based on the results of this study, we
      cautiously speculate that although neuroinflammation plays a role in the
      development of neurodegenerative diseases, including PD and dementia, it may be
      unrelated to the pathogenesis of dementia in patients with PD.

PMID- 23955614
TI  - Depression of local cell-mediated immunity and histological characteristics of
      disseminated AIDS-related Mycobacterium avium infection after the initiation of
      antiretroviral therapy.
AB  - OBJECTIVE: The aim of the present study was to examine the immunohistological
      characteristics of disseminated Mycobacterium avium infection after the
      initiation of antiretroviral therapy (ART) for acquired immunodeficiency syndrome
      (AIDS). METHODS: We histologically investigated five autopsied AIDS patients with
      systemic M. avium infection. RESULTS: The inflammatory cell composition in the
      affected tissues was assessed using immunohistochemistry. The celiac lymph nodes
      and intestinal canal were the most commonly involved organs in the AIDS cases.
      The most common histological feature was unstructured aggregation of histiocytes.
      Immunohistochemistry revealed depression of CD4(+), CD8(+) and CD57(+) cells in
      the gut lamina propria and mesenteric lymph nodes. CONCLUSION: These findings
      suggest that local cell-mediated immunity is depressed in affected tissues and
      that the primary histological feature is poor organization of granulomas in
      mycobacterial lesions, despite the administration of adequate ART.

PMID- 23955615
TI  - A novel SCN5A mutation demonstrating a variety of clinical phenotypes in familial
      sick sinus syndrome.
AB  - Mutations in SCN5A have been reported to cause several types of hereditary
      arrhythmias (overlap syndrome). We herein report two patients with the
      overlapping phenotypes of juvenile sick sinus syndrome (SSS) and Brugada syndrome
      (BrS). The proband was a man who was in his twenties and had been diagnosed with
      both SSS and ventricular tachycardia (VT). A pilsicainide challenge test revealed
      a coved type ST segment elevation. His teenage brother also suffered from SSS,
      but no VT had been documented. A pilsicainide challenge failed to produce a
      Brugada-type ST elevation, but there was a marked prolongation of the His
      ventricle interval. Their electrocardiograms at rest did not display any Brugada
      type ST elevations. We identified a novel SCN5A (F1775Lfs*15) mutation in both
      patients, even though there was a phenotype discrepancy. 

PMID- 23955616
TI  - Platypnea-orthodeoxia syndrome caused by a latent atrial septal defect.
AB  - A 79-year-old woman presented with unexplained hypoxia that became exacerbated by
      an upright posture (platypnea-orthodeoxia syndrome). A (99m)Tc-macroaggregated
      albumin pulmonary perfusion scan revealed a right to left shunt of 25.5% in the
      supine position and 32.3% in the sitting position. A dynamic CT scan and a
      transoesophageal echocardiogram confirmed the presence of a shunt across an
      atrial septal defect (ASD). A percutaneous transcatheter closure of the defect
      significantly improved the patient's blood oxygenation levels when she was in the
      upright position. An ASD should therefore be included in the differential
      diagnosis of platypnea-orthodeoxia syndrome, regardless of the patient's age. 

PMID- 23955617
TI  - Primary retroperitoneal diffuse large B-cell lymphoma presenting with numb chin
      syndrome and painful ophthalmoplegia.
AB  - Numb chin syndrome (NCS) and painful ophthalmoplegia (PO) are neurological
      syndromes associated with the disturbance of certain cranial nerves and their
      downstream nerves. These syndromes are caused by various diseases, and, in rare
      cases precede the diagnosis of systemic malignant lymphoma. We herein present the
      case of a 59-year-old man diagnosed simultaneously with NCS and PO caused by a
      tumor located around the cavernous sinus and with diffuse large B-cell lymphoma
      that was identified via biopsy of a large retroperitoneal tumor. He was
      successfully treated with a standard rituximab-containing chemotherapy combined
      with high-dose intravenous methotrexate and intrathecal chemotherapy. 

PMID- 23955618
TI  - Dolichoectatic vertebrobasilar dissecting aneurysm originating from
      atherosclerosis: an autopsy case.
AB  - We herein report an unusual case of profound brain infarction of the posterior
      circulation due to a dolichoectatic vertebrobasilar dissecting aneurysm (DVDA)
      originating from atherosclerosis. On autopsy, diffuse atherosclerosis was
      observed with a multi-fusiform aneurysm measuring 1 to 2 cm in diameter ranging
      from the left vertebral artery to the basilar artery. The microscopic findings of
      the aneurysm revealed severe stenosis of the artery caused by intimal thickening,
      intimal flap formation and thrombosis, indicating the presence of a dissecting
      aneurysm originating from atherosclerosis. The DVDA observed in this case was
      considered to be slowly progressive and associated with the development of
      atherosclerosis. The etiology of structural destabilization in patients with DVDA
      involves rupture of the internal elastic lamina, which is dislodged by massive
      hematomas that form atheromatous lesions. 

PMID- 23955619
TI  - An autopsy case of the Marburg variant of multiple sclerosis (acute multiple
      sclerosis).
AB  - We herein report an autopsy case of the Marburg variant of multiple sclerosis
      (MS). A 29-year-old woman developed acute and progressive neurological symptoms.
      A diagnosis of MS was suspected based on the patient's clinical background and
      brain MRI findings and the lack of evidence of malignancy on a brain biopsy.
      Despite the administration of typical treatment for MS, a fatal outcome occurred
      three months after disease onset. The autopsy revealed multiple inflammatory
      demyelinating lesions in the central nervous system. In addition, two noteworthy
      histopathological features were observed compared with prototypical MS. We
      evaluate the pathogenic differences between the Marburg type and prototypical MS
      by discussing the neuropathology and cerebrospinal fluid (CSF) findings of our
      case. 

PMID- 23955620
TI  - Glucocorticoid-induced normotensive scleroderma renal crisis: a report on two
      cases and a review of the literature in Japan.
AB  - We herein report the findings of 2 cases of normotensive scleroderma renal crisis
      (SRC) that developed soon after the commencement of a glucocorticoid therapy. We
      also review 8 cases of normotensive SRC reported in Japan, including our cases.
      The common characteristics of these 8 cases are as follows: the recent onset of
      systemic sclerosis, the presence of diffuse skin sclerosis, the presence of
      myositis and/or serositis, a high titer of antinuclear antibody and positivity
      for anti-Scl-70 antibody. In 7 of the 8 patients, thrombotic microangiopathy
      developed within one month of starting the glucocorticoid treatment. We should be
      careful with the use of glucocorticoids in systemic sclerosis patients exhibiting
      these features in order to avoid cases of normotensive SRC. 

PMID- 23955621
TI  - Sweet's syndrome complicated by Kikuchi's disease and hemophagocytic syndrome
      which presented with retinoic acid-inducible gene-I in both the skin epidermal
      basal layer and the cervical lymph nodes.
AB  - A 21-year-old man was admitted to our hospital with a fever, erythema, cervical
      lymphadenopathy and pancytopenia. A diagnosis of Sweet's syndrome (SS) with
      Kikuchi's disease (KD) and hemophagocytic syndrome (HPS) was made based on the
      results of a bone marrow aspiration along with the results from biopsy specimens
      of the brachial skin and a cervical lymph node. The expression of retinoic acid
      inducible gene-I (RIG-I) in the skin epidermal basal layer as well as in a
      cervical lymph node was revealed through immunohistochemistry. He successfully
      entered remission through treatment with prednisolone. This findings of this case
      indicate that when SS with KD presents as HPS, it may suggest an association with
      an RIG-I-related innate immunity. 

PMID- 23955622
TI  - Abrupt chest pain in a pregnant woman.

PMID- 23955623
TI  - Bronchopneumonia caused by Corynebacterium pseudodiphtheriticum.

PMID- 23955624
TI  - Spontaneous internal jugular vein thrombosis associated with lung cancer.

PMID- 23955625
TI  - It is time to reconsider position of metabolic syndrome in preventive medicine.

PMID- 23955626
TI  - Reducing risks to health: what can we learn from the Global Burden of Disease
      2010 Study?

PMID- 23955627
TI  - Multiple lymphomatous polyposis form of blastoid variant of mantle cell lymphoma
      in colon: a case report and review of literature.

PMID- 23955628
TI  - Chronological age vs biological age: an age-related normogram for antral follicle
      count, FSH and anti-Mullerian hormone.
AB  - OBJECTIVE: To evaluate the correlation between chronological and biological age
      by comparing the normograms of AFC, AMH, and FSH. DESIGN: Retrospective study
      SETTING: Data were taken from patients who visited the Infertility Clinic at Dr.
      Cipto Mangunkusumo General Hospital Jakarta, Indonesia, between January 2008 and
      December 2010. PATIENT(S): Infertile women who visited the Infertility Clinic.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Normogram of AFC (n = 366), AMH
      (n = 1616) and FSH (n = 415). RESULT(S): The correlations among AFC, AMH, FSH,
      and age are statistically significant. Normograms of AFC and AMH with 3rd, 10th,
      25th, 50th, 75th, 90th, and 97th percentiles showed a decrease in age where FSH
      increased. A cut-off value of AFC, AMH, and FSH for poor responders was plotted
      at the 50th percentile of each normogram. Serum AMH and AFC started to decline in
      women between 34 and 35 years old. We found a relatively lower slope increase of
      FSH in older patients compared to that of AFC and AMH. FSH was observed to be a
      later predictor of biological age than AMH and AFC. CONCLUSION(S): AMH predicted
      biological age earlier than FSH or AFC. Normograms can provide a reference guide
      for physicians to counsel infertile women. However, future validation with
      longitudinal data is still needed.

PMID- 23955629
TI  - Theory of the kinetics of luminescence and its temperature dependence for Ag
      nanoclusters dispersed in a glass host.
AB  - We have measured and fitted the kinetics of luminescence of Ag nanoclusters
      homogeneously dispersed within the bulk of an oxyfluoride glass, with various
      sample temperatures. The balance equations for the populations of the excited
      singlet and triplet states of the Ag nanoclusters are proposed and used in this
      fitting while taking into account inter-system crossing between the singlet and
      triplet states and their wavelength dependent spontaneous decay to the ground
      singlet state. The involved energy barriers and rate constants and spontaneous
      emission cross-sections for the excited singlet and triplet states are evaluated.

PMID- 23955630
TI  - Crystal structures of the two membrane-proximal Ig-like domains (D3D4) of
      LILRB1/B2: alternative models for their involvement in peptide-HLA binding.
AB  - Leukocyte immunoglobulin-like receptors (LILRs), also called CD85s, ILTs, or
      LIRs, are important mediators of immune activation and tolerance that contain
      tandem immunoglobulin (Ig)-like folds. There are 11 (in addition to two
      pseudogenes) LILRs in total, two with two Ig-like domains (D1D2) and the
      remaining nine with four Ig-like domains (D1D2D3D4). Thus far, the structural
      features of the D1D2 domains of LILR proteins are well defined, but no structures
      for the D3D4 domains have been reported. This is a very important field to be
      studied as it relates to the unknown functions of the D3D4 domains, as well as
      their relative orientation to the D1D2 domains on the cell surface. Here, we
      report the crystal structures of the D3D4 domains of both LILRB1 and LILRB2. The
      two Ig-like domains of both LILRB1-D3D4 and LILRB2-D3D4 are arranged at an acute
      angle (~60 degrees ) to form a bent structure, resembling the structures of
      natural killer inhibitory receptors. Based on these two D3D4 domain structures
      and previously reported D1D2/HLA I complex structures, two alternative models of
      full-length (four Ig-like domains) LILR molecules bound to HLA I are proposed.

PMID- 23955631
TI  - Sprouty4 regulates endothelial cell migration via modulating integrin beta3
      stability through c-Src.
AB  - Angiogenesis is mediated by signaling through receptor tyrosine kinases (RTKs),
      Src family kinases and adhesion receptors such as integrins, yet the mechanism
      how these signaling pathways regulate one another remains incompletely
      understood. The RTK modulator, Sprouty4 (Spry4) inhibits endothelial cell
      functions and angiogenesis, but the mechanisms remain to be fully elucidated. In
      this study, we demonstrate that Spry4 regulates angiogenesis in part by
      regulating endothelial cell migration. Overexpression of Spry4 in human
      endothelial cells inhibited migration and adhesion on vitronectin (VTN), whereas
      knockdown of Spry4 enhanced these behaviors. These activities were shown to be c
      Src-dependent and Ras-independent. Spry4 disrupted the crosstalk between vascular
      endothelial growth factor-2 and integrin alphaVbeta3, the receptor for VTN. Spry4
      overexpression resulted in decreased integrin beta3 protein levels in a post
      transcriptional manner in part by modulating its tyrosine phosphorylation by c
      Src. Conversely, knockdown of Spry4 resulted in increased integrin beta3 protein
      levels and tyrosine phosphorylation. Moreover, in vivo analysis revealed that
      Spry4 regulated integrin beta3 levels in murine embryos and yolk sacs. Our
      findings identify an unanticipated role for Spry4 in regulating c-Src activity
      and integrin beta3 protein levels, which contributes to the regulation of
      migration and adhesion of endothelial cells. Thus, targeting Spry4 may be
      exploited as a target in anti-angiogenesis therapies. 

PMID- 23955632
TI  - Preclinical evaluation of BAY 1075553, a novel (18)F-labelled inhibitor of
      prostate-specific membrane antigen for PET imaging of prostate cancer.
AB  - PURPOSE: Prostate-specific membrane antigen (PSMA) is a transmembrane protein
      overexpressed in prostate cancer and is therefore being explored as a biomarker
      for diagnosing and staging of the disease. Here we report preclinical data on BAY
      1075553 (a 9:1 mixture of (2S,4S)- and (2R,4S)-2-[(18)F]fluoro-4-phosphonomethyl
      pentanedioic acid), a novel (18)F-labelled small molecule inhibitor of PSMA
      enzymatic activity, which can be efficiently synthesized from a direct
      radiolabelling precursor. METHODS: The (18)F-radiolabelled stereoisomers of 2
      [(18)F]fluoro-4-(phosphonomethyl)-pentanedioic acid were synthesized from their
      respective isomerically pure precursors dimethyl 2
      {[bis(benzyloxy)phosphoryl]methyl}-4-(tosyloxy)pentanedioate. In vivo positron
      emission tomography (PET) imaging and biodistribution studies were conducted in
      mice bearing LNCaP, 22Rv1 and PC-3 tumours. Pharmacokinetic parameters and
      dosimetry estimates were calculated based on biodistribution studies in rodents.
      For non-clinical safety assessment (safety pharmacology, toxicology) to support a
      single-dose human microdose study, off-target effects in vitro, effects on vital
      organ functions (cardiovascular in dogs, nervous system in rats), mutagenicity
      screens and an extended single-dose study in rats were conducted with the non
      radioactive racemic analogue of BAY 1075553. RESULTS: BAY 1075553 showed high
      tumour accumulation specific to PSMA-positive tumour-bearing mice and was
      superior to other stereoisomers tested. Fast clearance of BAY 1075553 resulted
      overall in low background signals in other organs except for high uptake into
      kidney and bladder which was mainly caused by renal elimination of BAY 1075553. A
      modest uptake into bone was observed which decreased over time indicating organ
      specific uptake as opposed to defluorination of BAY 1075553 in vivo.
      Biodistribution studies found highest organ doses for kidneys and the urinary
      bladder wall resulting in a projected effective dose (ED) in humans of 0.0219
      mSv/MBq. Non-clinical safety studies did not show off-target activity, effects on
      vital organs function or dose-dependent adverse effects. CONCLUSION: BAY 1075553
      was identified as a promising PET tracer for PSMA-positive prostate tumours in
      preclinical studies. BAY 1075553 can be produced using a robust, direct
      radiosynthesis procedure. Pharmacokinetic, toxicology and safety pharmacology
      studies support the application of BAY 1075553 in a first-in-man microdose study
      with single i.v. administration.

PMID- 23955633
TI  - Uptake and use of recommendations for the diagnosis, severity scoring and
      management of chronic GVHD: an international survey of the EBMT-NCI Chronic GVHD
      Task Force.
AB  - In 2005, the National Institutes of Health (NIH) consensus conference published a
      series of papers recommending methods to improve the conduct of clinical trials
      in chronic GVHD. Although the NIH recommendations were primarily aimed at
      strengthening research, several papers addressed issues relevant for clinical
      practice, particularly diagnosis, severity scoring, and ancillary and supportive
      care practices. We conducted an international survey to assess the uptake of
      these recommendations, identify barriers to greater use and document the use and
      perceived effectiveness of available treatments. The response rate for the
      American survey of 1387 practitioners was 21.8%, and it was 24.6% for 407 centers
      surveyed in Europe, Asia, Australia and Africa. Most respondents were familiar
      with the NIH consensus recommendations (94-96%) and used them in practice.
      Multiple barriers to greater use were reported. Besides lack of time (55-62%),
      unfamiliarity with the recommendations, scarcity of evidence supporting the
      impact of recommendations on outcomes, insufficient training/experience in
      chronic GVHD management and inaccessibility of subspecialists were also endorsed.
      Systemic corticosteroids were reported to be the most effective treatment for
      chronic GVHD, but many others were perceived to have moderate or great success.
      Therapeutic management of steroid-refractory chronic GVHD was identified as the
      highest priority for research. 

PMID- 23955635
TI  - Risk factor analysis of idiopathic pneumonia syndrome after allogeneic
      hematopoietic SCT in children.
AB  - Idiopathic pneumonia syndrome (IPS) is a critical complication following
      allogeneic hematopoietic SCT (HSCT); however, few reports have analyzed the risk
      factors for IPS in children. A total of 210 consecutive pediatric patients,
      including 131 boys and 79 girls, with various hematologic malignancies, aplastic
      anemia or solid tumors who underwent allogeneic HSCT were analyzed to clarify the
      incidence and risk factors for IPS. Patient and transplantation characteristics
      after allogeneic HSCT were compared between patients with and without IPS.
      Cumulative incidence rates of IPS 120 days after allogeneic HSCT were 6.7%
      (14/210). Of 14 patients with IPS, 11 (78.6%) died after developing IPS. The
      presence of prior HSCT was more frequent in patients with IPS (IPS group) than in
      those without IPS (non-IPS group; 35.7 vs 12.8%, respectively, P=0.018). The IPS
      group contained more patients with acute GVHD (grade II-IV) than the non-IPS
      group (50.0 vs 18.9%, respectively, P=0.006). The association of these two
      factors with IPS was further confirmed by multivariate analysis. We should be
      aware of these risk factors in patients who have undergone allogeneic HSCT. 

PMID- 23955634
TI  - Impact of HLA mismatch direction on outcomes after umbilical cord blood
      transplantation for hematological malignant disorders: a retrospective Eurocord
      EBMT analysis.
AB  - HLA matching is a critical determinant of outcomes for patients who have
      undergone umbilical cord blood transplantation (UCBT). Data have been published
      on the importance of donor/recipient HLA mismatch direction on UCBT outcomes. HLA
      mismatch in the graft-versus-host (GVH) direction is defined as a donor
      homozygous at an HLA locus, while the recipient shares one HLA Ag with the donor.
      HLA mismatch in the host-versus-graft (HVG) direction is defined as a recipient
      homozygous with the donor sharing one HLA Ag. In our study we focused on
      confirming, using an independent population, whether transplantation outcomes
      would be different when HLA mismatch direction was considered. We analyzed 1565
      patients who received a single-unit UCBT for malignant disease. Median age was 15
      years and 72% of patients were transplanted for leukemia. In multivariate
      analysis, using the 5/6 HLA-matched population as reference, one or two HLA
      mismatches in the GVH or HVG direction were not associated with non-relapse
      related mortality and survival. On the basis of our results, there is no evidence
      to support a change in the current practice for cord blood unit selection. 

PMID- 23955636
TI  - Impact of being overweight on outcomes of hematopoietic SCT: a meta-analysis.
AB  - The impact of being overweight on outcome after hematopoietic SCT (HSCT) is
      controversial. We performed meta-analyses to evaluate the impact of being
      overweight on acute graft-versus-host disease (aGVHD) risk and survival. Original
      data were obtained from MEDLINE, and studies that evaluated being overweight
      before transplantation in recipients as a risk factor for aGVHD or a prognostic
      factor for overall survival (OS) were extracted. Study-specific relative risks on
      the log scale comparing overweight with non-overweight patients were used to
      obtain a pooled RR with 95% confidence interval (CI). We identified 8 studies of
      aGVHD and 21 of OS. In allogeneic HSCT, the meta-analysis determined
      statistically significant associations of overweight recipients with aGVHD risk
      and OS. Meta-analysis of the 8 studies of aGVHD indicated that the RR for
      overweight to non-overweight patients was 1.186 (95% CI: 1.072-1.312). Regarding
      OS, meta-analysis of 11 allogeneic HSCT studies indicated that the RR for
      overweight to non-overweight patients was 1.163 (1.009-1.340). Our results
      indicate that being overweight before transplantation in recipients is associated
      with a high aGVHD rate and worse survival after allogeneic HSCT. Potential
      heterogeneity especially in adult/pediatric patients limits the interpretability
      of our finding. Further, well-designed large cohort studies are warranted. 

PMID- 23955637
TI  - Impact of palifermin on intestinal mucositis of HSCT recipients after BEAM.
AB  - The matched-control study failed to show a clinical relevant impact of palifermin
      on intestinal mucositis, although there was a reduced inflammatory response and
      less febrile neutropenia among patients who had no bacteraemia. 

PMID- 23955638
TI  - Multiple sclerosis: Prospects and promise.
AB  - We have entered a golden era in multiple sclerosis (MS) research. Two decades
      ago, our understanding of the disease was largely descriptive and there were no
      approved therapies to modify the natural history of MS. Today, delineation of
      immune pathways relevant to MS have been clarified; a comprehensive map of genes
      that influence risk compiled; clues to environmental triggers identified;
      noninvasive in vivo monitoring of the MS disease process has been revolutionized
      by high-field MRI; and many effective therapies for the early, relapsing,
      component of MS now exist. However, major challenges remain. We still have no
      useful treatment for progressive MS (the holy grail of MS research), no means to
      repair injured axons or protect neurons, and extremely limited evidence to guide
      treatment decisions. Recent advances have set in place a foundation for
      development of increasingly selective immunotherapy for patients; application of
      genetic and genomic discoveries to improve therapeutic options; development of
      remyelination or neuroprotection therapies for progressive MS; and integrating
      clinical, imaging and genomic data for personalized medicine. MS has now advanced
      from the backwaters of autoimmune disease research to the front-line, and
      definitive answers, including cures, are now realistic goals for the next decade.
      Many of the breakthrough discoveries in MS have also resulted from meaningful
      interactions across disciplines, and especially from translational and basic
      scientists working closely with clinicians, highlighting that the clinical value
      of discoveries are most often revealed when ideas developed in the laboratory are
      tested at the bedside.

PMID- 23955639
TI  - Evaluating cis-2,6-dimethylpiperidide (cis-DMP) as a base component in lithium
      mediated zincation chemistry.
AB  - Most recent advances in metallation chemistry have centred on the bulky secondary
      amide 2,2,6,6-tetramethylpiperidide (TMP) within mixed metal, often ate,
      compositions. However, the precursor amine TMP(H) is rather expensive so a
      cheaper substitute would be welcome. Thus this study was aimed towards developing
      cheaper non-TMP based mixed-metal bases and, as cis-2,6-dimethylpiperidide (cis
      DMP) was chosen as the alternative amide, developing cis-DMP zincate chemistry
      which has received meagre attention compared to that of its methyl-rich
      counterpart TMP. A new lithium diethylzincate, [(TMEDA)LiZn(cis-DMP)Et2]
      (TMEDA=N,N,N',N'-tetramethylethylenediamine) has been synthesised by co
      complexation of Li(cis-DMP), Et2Zn and TMEDA, and characterised by NMR (including
      DOSY) spectroscopy and X-ray crystallography, which revealed a dinuclear contact
      ion pair arrangement. By using N,N-diisopropylbenzamide as a test aromatic
      substrate, the deprotonative reactivity of [(TMEDA)LiZn(cis-DMP)Et2] has been
      probed and contrasted with that of the known but previously uninvestigated di
      tert-butylzincate, [(TMEDA)LiZn(cis-DMP)tBu2]. The former was found to be the
      superior base (for example, producing the ortho-deuteriated product in respective
      yields of 78% and 48% following D2O quenching of zincated benzamide
      intermediates). An 88% yield of 2-iodo-N,N-diisopropylbenzamide was obtained on
      reaction of two equivalents of the diethylzincate with the benzamide followed by
      iodination. Comparisons are also drawn using 1,1,1,3,3,3-hexamethyldisilazide
      (HMDS), diisopropylamide and TMP as the amide component in the lithium amide,
      Et2Zn and TMEDA system. Under certain conditions, the cis-DMP base system was
      found to give improved results in comparison to HMDS and diisopropylamide (DA),
      and comparable results to a TMP system. Two novel complexes isolated from
      reactions of the di-tert-butylzincate and crystallographically characterised,
      namely the pre-metallation complex [{(iPr)2N(Ph)C=O}LiZn(cis-DMP)tBu2] and the
      post-metallation complex [(TMEDA)Li(cis-DMP){2-[1-C(=O)N(iPr)2]C6H4}Zn(tBu)],
      shed valuable light on the structures and mechanisms involved in these alkali
      metal-mediated zincation reactions. Aspects of these reactions are also modelled
      by DFT calculations.

PMID- 23955640
TI  - Particle tracking microrheology of purified gastrointestinal mucins.
AB  - The rheological characteristics of gastric and duodenal mucin solutions, the
      building blocks of the mucus layer that covers the epithelia of the two organs,
      were investigated using particle tracking microrheology. We used biochemically
      well characterized purified porcine mucins (MUC5AC and MUC2) as models for human
      mucins, to probe their viscoelasticity as a function of mucin concentration and
      pH. Furthermore, we used both reducing (dithiothreitol, DTT) and chaotropic
      agents (guanidinium chloride and urea) to probe the mesoscopic forces that
      mediate the integrity of the polymer network. At neutral pH both gastric and
      duodenal mucins formed self-assembled semi-dilute networks above a certain
      critical mucin concentration (c*) with the viscosity (eta) scaling as
      eta~c(0.53+/-0.08) for MUC5AC and eta~c(0.53+/-0.06) for MUC2, where c is the
      mucin concentration. Above an even higher mucin concentration threshold (ce , the
      entanglement concentration) reptation occurs and there is a dramatic increase in
      the viscosity scaling, eta~c(3.92+/-0.38) for MUC5AC and eta~c(5.1+/-0.8) for
      MUC2. The dynamics of the self-assembled comb polymers is examined in terms of a
      scaling model for flexible polyelectrolyte combs. Both duodenum and gastric mucin
      are found to be pH switchable gels, gelation occurring at low pHs. There is a
      hundred-fold increase in the elastic shear modulus once the pH is decreased. The
      addition of DTT, guanidinium chloride and urea disassembles both the semi-dilute
      and gel structures causing a large increase in the compliance (decrease in their
      shear moduli). Addition of the polyphenol EGCG has a reverse effect on mucin
      viscoelasticity, that is, it triggers a sol-gel transition in semi-dilute mucin
      solutions at neutral pH.

PMID- 23955642
TI  - Enhanced reconstruction of rat calvarial defects achieved by plasma-treated
      electrospun scaffolds and induced pluripotent stem cells.
AB  - Tissue engineering with a combination of stem cells and nanofibrous scaffolds has
      attracted interest with regard to bone regeneration applications. In the present
      study, human induced pluripotent stem cells (iPSCs) were cultured on polymeric
      nanofibrous polyethersulfone (PES) with and without plasma treatment. The
      capacity of PES and plasma-treated PES (Plasma-PES) scaffolds to support the
      proliferation and osteogenic differentiation of iPSCs was investigated by MTT
      assay and for common osteogenic markers such as alkaline phosphatase activity,
      calcium mineral deposition and bone-related genes. Plasma-PES scaffolds with or
      without iPSCs were subsequently used to evaluate bone regeneration of critical
      size defects in the rat by digital mammography, multislice spiral-computed
      tomography imaging and histological analysis. The results of in vitro analysis
      showed that plasma treatment significantly enhanced iPSC proliferation and
      osteogenesis. After 8 weeks of iPSC-loaded Plasma-PES implantation, no mortality
      or complication was observed in animals or at the site of surgery. Imaging
      analysis revealed more extensive bone reconstruction in rats receiving nanofibers
      compared with untreated control groups. Moreover, Plasma-PES seeded with iPSCs
      induced the highest regeneration of bone defects among all groups. These findings
      were confirmed by histological staining. Affective osseointegration was observed
      in implanted scaffolds. Thus, plasma-treated nanofibrous scaffolds are suitable
      tissue-engineered matrices for supporting the proliferation and osteogenic
      differentiation of iPSCs and might also be appropriate for the reconstruction of
      bone defects.

PMID- 23955643
TI  - Distribution of neuropeptides in the antennal lobes of male Spodoptera
      littoralis.
AB  - Olfaction is an important sensory modality that regulates a plethora of
      behavioural expressions in insects. Processing of olfactory information takes
      place in the primary olfactory centres of the brain, namely the antennal lobes
      (ALs). Neuropeptides have been shown to be present in the olfactory system of
      various insect species. In the present study, we analyse the distribution of
      tachykinin, FMRFamide-related peptides, allatotropin, allatostatin, myoinhibitory
      peptides and SIFamide in the AL of the male Egyptian cotton leafworm, Spodoptera
      littoralis. Immunocytochemical analyses revealed that most neuropeptides were
      expressed in different subpopulations of AL neurons. Their arborisation patterns
      within the AL suggest a significant role of neuropeptide signalling in the
      modulation of AL processing. In addition to local interneurons, our analysis also
      revealed a diversity of extrinsic peptidergic neurons that connected the antennal
      lobe with other brain centres. Their distributions suggest that extrinsic neurons
      perform various types of context-related modulation. 

PMID- 23955641
TI  - Molecular status of pituitary carcinoma and atypical adenoma that contributes the
      effectiveness of temozolomide.
AB  - There have been several reports of temozolomide (TMZ) treatment of pituitary
      carcinomas and atypical adenomas. O(6)-methyl-guanine-DNA methyltransferase is
      not the sole molecule determining the sensitivity to TMZ in pituitary carcinomas
      and atypical adenomas. The Japan Society of Hypothalamic and Pituitary Tumors
      study suggests that MSH6, one of mismatch repair pathway enzyme, fulfills a
      contributory role to the efficacy of TMZ treatment for pituitary carcinomas and
      atypical adenomas. The preserved MSH6 function might be essential for the
      responsiveness to TMZ treatment in pituitary carcinomas and atypical adenomas. 

PMID- 23955644
TI  - Completeness of case ascertainment at the Irish National Cancer Registry.
AB  - BACKGROUND: Cancer registries play a major role in cancer control, including
      quantifying the burden of cancer in the population, informing health service
      planning, and evaluating service provision. Registries must achieve a high level
      of completeness of case ascertainment. AIM: Completeness of case ascertainment
      for the National Cancer Registry (NCR) in Ireland was estimated. METHODS: For all
      invasive cancers, and the four most common sites, we used two quantitative
      methods which use information from death certificates to obtain estimates of
      completeness of registration-the Lincoln-Petersen (LP) estimator (which provides
      a lower bound estimate) and the flow method (which estimates completeness at a
      fixed time-point, in this case 5 years). Data were extracted at the end of 2010.
      Independent case ascertainment was used to assess completeness of breast cancer
      registration in the 50-64 age group and of rectal cancer in surgical patients
      diagnosed in 2007. RESULTS: Completeness of case ascertainment was >99 % for the
      breast screening age-group and for surgical rectal cancer cases. A lower bound on
      completeness of case ascertainment for all invasive cancers excluding non
      melanoma skin cancers is 94.3 % using the LP estimator. The estimate from the
      flow method is 97 % after 5 years, [95 % confidence interval (96.2 %, 97.7 %)].
      Five-year levels of completeness for the four commonest cancers using the flow
      method were: colorectal, 97.4 %; lung, 98.7 %; prostate, 95.8 % and breast, 98.0
      %. CONCLUSION: The estimated levels of completeness for the NCR are satisfactory.
      Further work is required to compare the methods used.

PMID- 23955645
TI  - Heat-shock proteins in stromal joint tissues: innocent bystanders or disease
      initiating proteins?
AB  - Heat-shock proteins (HSPs) are molecular chaperones that are highly conserved
      between species. In recent decades it has become clear that these proteins play
      an important role in the pathogenesis of inflammatory and degenerative joint
      diseases by (dys)regulating the immune system and by direct effects on the
      stromal tissues of the joint. In this review we discuss current insights into the
      expression pattern of HSPs in connective tissues, the direct biological role of
      HSPs in stromal tissues and the potential clinical applications.

PMID- 23955646
TI  - Usability of an innovative and interactive electronic system for collection of
      patient-reported data in axial spondyloarthritis: comparison with the traditional
      paper-administered format.
AB  - OBJECTIVE: To evaluate the validity, in terms of the patients' acceptance,
      preference, feasibility and reliability of an innovative, interactive
      computerized system for collection of patient-reported outcome (PRO) data on
      axial SpA against the paper-and-pencil version. METHODS: Fifty-five patients with
      axial SpA completed both the touch screen and the paper-and-pencil set of
      questionnaires. A computerized touch-screen system, SPEAMonitor, was developed to
      capture PRO data. Variables recorded included demographic data, patient's
      assessment of general health status, BASDAI, BASFI, BASMI and acute-phase
      reactant levels. In order to assess the patient's acceptance of, preference for
      and feasibility of computer-based questionnaires, the participants filled in an
      additional questionnaire. The time taken to complete both formats was measured.
      In a further test-retest study, 25 patients were re-evaluated. RESULTS: The
      agreement between the paper-administered and computer touch-screen format of the
      BASFI, BASDAI questionnaires and the Ankylosing Spondylitis Disease Activity
      Scores was excellent. Intraclass correlation coefficients (ICCs) between data
      ranged from 0.90 to 0.96. Additionally the test-retest study showed a very good
      agreement between the scores for the two administrations (ICC >= 0.90). Age,
      computer experience and education level had no significant impact on the results.
      The computerized questionnaires were reported to be easier to use. The mean time
      spent completing the questionnaires on a touch screen was 5.1 min and on paper
      7.9 min. CONCLUSION: Our newly developed computer-assisted touch-screen
      questionnaires for PRO in axial SpA were well accepted by patients, with good
      data quality, reliability and score agreement.

PMID- 23955647
TI  - Vitamin D deficiency does not predict progression of coronary artery calcium,
      carotid intima-media thickness or high-sensitivity C-reactive protein in systemic
      lupus erythematosus.
AB  - OBJECTIVE: Vitamin D deficiency is common in SLE. Cardioprotective effects of
      vitamin D have been postulated due to modulation of inflammatory cytokines.
      However, the effects of vitamin D supplementation on inflammatory cytokines in
      trials have been inconsistent. We determined whether levels of vitamin D at
      baseline were associated with subclinical measures of atherosclerosis, or with
      changes in subclinical measures over 2 years. METHODS: Of the 200 patients
      enrolled in the Lupus Atherosclerosis Prevention Study, complete baseline and
      follow-up data [including coronary artery calcium (CAC), carotid intima-media
      thickness (IMT), 25-hydroxy vitamin D [25(OH)D] and high-sensitivity CRP (hsCRP)
      levels] were available for 154 patients. Assessments were repeated 2 years later.
      RESULTS: 25(OH)D values ranged from 4 to 79 ng/ml. Among African American
      patients, 25(OH)D values ranged from 4 to 55 ng/ml. With low 25(OH)D (vitamin D
      <21 ng/ml), a higher proportion had a CAC score >100 (11%) compared with those
      with vitamin D insufficiency (21-32 ng/ml) (10%) and normal (>=32 ng/ml) 25(OH)D
      (3%), which was not statistically significant. 25(OH)D was neither associated
      with nor did it predict progression of CAC or carotid IMT over 2 years. The mean
      hsCRP decreased over 2 years. CONCLUSION: 25(OH)D was not associated with any
      measure of subclinical atherosclerosis. 25(OH)D deficiency was associated with
      higher hsCRP at baseline, but did not predict a change in hsCRP over 2 years.

PMID- 23955648
TI  - Disease assessment in Takayasu's arteritis.

PMID- 23955649
TI  - Danon disease. A novel mutation in the LAMP-2 gene and ophthalmic abnormality.

PMID- 23955650
TI  - Association with and predictive capacity of self-perceived risk of falling in
      recurrent falls in older people: a prospective study.
AB  - OBJECTIVE: Given the impact of recurrent falls in older people, risk evaluation
      for falling is an important part of geriatric assessment. Available clinical
      tools usually do not include patients' self-perceived risk of falling. The
      objective of this study was to evaluate association with and predictive capacity
      of self-perceived risk of falling in recurrent falls. METHODS: Prospective cohort
      study. Patients attending a geriatric outpatients' clinic were recruited
      (Pfeiffer score <5). A baseline assessment and follow-up over 14 months was
      scheduled for each patient. Self-perceived risk of falling was assessed through
      four questions. Association with falls was evaluated through relative risk,
      survival curves (Kaplan-Meier), and Cox regression (recurrent falls as outcome
      variables). Predictive capacity was evaluated through sensitivity, specificity,
      and predictive values. RESULTS: 52 participants answered all 4 questions, and 15
      participants (27.2 %) presented recurrent falls. Question 1 (Do you think you may
      fall in the next few months?) was associated with the occurrence of recurrent
      falls according to relative risk [3.88 (CI95 %:1.48-10.09)] and survival curves
      (log Rank, p 0.004). Such relationship is maintained over time. Cox-regression
      also showed significant difference in relation to the answer for question 1 and
      recurrent falls [hazard ratio 4.044 (CI: 1.410-11.597); p 0.009]. Sensitivity,
      specificity, positive and negative predictive values (question 1) were 53.3 %
      (CI95 %:28.1-78.6), 84.2 % (CI95 %:72.6-95.8), 57.1 % (CI95 %:31.2-83.1), and
      82.1 % (CI95 %:70.0-94.1), respectively. CONCLUSIONS: Patients' self-perceived
      risk of falling is related to recurrent falls amongst people with a high risk of
      falling and this parameter might be useful in falling risk evaluation.

PMID- 23955651
TI  - Inequality in workplace conditions and health outcomes.
AB  - This paper examines the relationship between the inequality in workplace
      conditions and health-related outcomes in Japan. It analyzes the effect of
      changes in the work conditions and work arrangements on the subjective health,
      activity restriction, and depression symptoms, using the Japanese Life Course
      Panel Survey (JLPS). The 2007 JLPS consists of nationally representative sample
      of the youth (20 to 34 yr old) and the middle-aged (35 to 40 yr old). The
      original respondents were followed up in 2008, and 2,719 respondents for the
      youth panel and 1,246 for the middle-aged panel returned the questionnaires. The
      first major conclusion is that there are substantial changes in health conditions
      between the two waves even though the distributions of health-related outcomes
      are very similar at two time points. The second major conclusion is that the
      effects of work conditions depend on different health-related outcomes. Self
      reported health and depression symptoms are affected by a variety of job-related
      factors. The atmosphere of helping each other and the control over the pace of
      work are two important factors which affect both depression and self-reported
      health. All these findings suggest that the workplace conditions and job
      characteristics have profound influence on the workers' health.

PMID- 23955652
TI  - Being out of work and health among younger Japanese men: a panel data analysis.
AB  - This paper examines the effect of being out of work, which is in a broader
      category of unemployment, on the physical and mental health of younger Japanese
      men using panel data. A fixed effects model, widely used to control for
      unobserved individual heterogeneity in panel data analysis, was used for this
      analysis. Using the first through the fifth waves of the Japanese Life Course
      Panel Survey, the first wave of which was conducted with people aged 20-40 yrs in
      2007, it is found that being out of work has no observable effect on self
      assessed physical health. However, being out of work has a negative effect on
      mental health as measured by the five-item version of the Mental Health
      Inventory. It is difficult to clearly distinguish the direction of causality even
      after controlling for individual heterogeneity that is constant over time. An
      analysis was done with a sub-sample to mitigate a possible reverse causality. The
      results consistently show that being out of work has a negative effect on mental
      health.

PMID- 23955653
TI  - Estimates of annual medical costs of work-related low back pain in Japan.
AB  - Little is reported regarding economic burden of work-related low back pain except
      for the United States. In the present study, annual medical cost of work-related
      low back pain in Japan was calculated based on the treatment fee per day, a total
      of days of treatment received for low-back pain of all causes, employment rates,
      and an estimated number of work-related low-back cases. The analysis indicated
      that, in 2011, the total annual medical cost for work-related low back pain was
      82.14 billion yen, consisting of 26.48 and 55.66 billion yen for inpatients and
      outpatients, respectively. As well as for 2011, the costs were also estimated for
      2008, 2005, and 2002. Whereas the total medical costs of work-related low back
      pain monotonically increased during 2002-2011, the costs for spine disorder
      (including spondylosis) have also increased in recent years. Work-related low
      back pain entails a considerable economic burden to Japanese society. 

PMID- 23955654
TI  - The clock gene brain and muscle Arnt-like protein-1 (BMAL1) is involved in hair
      growth.
AB  - It is known that baldness caused by androgenetic alopecia is involved with
      androgen and the androgen receptor. Furthermore, it has been reported that
      testosterone secretion follows a circadian rhythm. Therefore, we hypothesized
      that a relationship exists between androgen-induced alopecia and biological
      rhythm. The mammalian circadian rhythm is controlled by several clock genes.
      Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1
      (BMAL1), one of the clock genes, is a transcription factor that plays central
      roles in the regulation of circadian rhythms. In this study, we investigated the
      influence of BMAL1 on hair follicle functions and hair growth. Mice deficient in
      BMAL1 expression exhibited a delay in hair regrowth after shaving. In hair
      follicles of mouse vibrissa, expression of Bmal1 and other clock genes was found
      to be rhythmic. Knockdown of BMAL1 in human follicle dermal papilla cells
      resulted in modulation of expression of several hair growth-related genes.
      Therefore, we concluded that expression of clock genes in hair follicles is
      linked to the circadian rhythm and that BMAL1 can regulate hair growth. 

PMID- 23955655
TI  - Identification of a possible respiratory arsenate reductase in Denitrovibrio
      acetiphilus, a member of the phylum Deferribacteres.
AB  - Denitrovibrio acetiphilus N2460(T) is one of the few members of the phylum
      Deferribacteres with a sequenced genome. N2460(T) was capable of growing with
      dimethyl sulfoxide, selenate, or arsenate provided as a terminal electron
      acceptor, and we identified 15 genes that could possibly encode respiratory
      reductases for these compounds. The protein encoded by one of these genes,
      YP_003504839, clustered with respiratory arsenate reductases on a phylogenetic
      tree. Transcription of the gene for YP_003504839, Dacet_2121, was highly induced
      when arsenate was provided as a terminal electron acceptor. Dacet_2121 exists in
      a possible operon that is distinct from the previously characterized respiratory
      arsenate reductase operon in Shewanella sp. ANA-3. 

PMID- 23955656
TI  - Helicity Induction in Three pi-Conjugated Chromophores by Planar Chirality of
      Calixamide.
AB  - Shall we twist? Three-dimensional arrangement of pi-conjugated chromophores with
      triple-stranded helicity was achieved by using the planar chirality of m
      calix[3]amide. Based on spectroscopic data and theoretical calculations, the
      dynamic and preferred helical characters of bithiophene units embedded in the
      tubular molecule were elucidated, and the absolute configuration was determined. 

PMID- 23955657
TI  - Associations of sex trafficking history with recent sexual risk among HIV
      infected FSWs in India.
AB  - History of forced or coerced sex work entry and/or sex work entry prior to age 18
      (i.e., sex trafficking) relate to early HIV risk; whether such risk persists is
      unclear. The current study assessed associations of reported sex trafficking
      histories and recent sexual risk among adult HIV-infected female sex workers
      (FSWs; n = 211) in Mumbai, India. Approximately one-half reported entering sex
      work prior to age 18 (50.2 %) or being forced or coerced into sex work (41.7 %).
      Past 90-day unprotected transactional sex was more prevalent among FSWs entering
      as minors than those entering as adults (AOR 2.06); in contrast, being forced or
      coerced into sex work related to reduction in such risk for HIV transmission (AOR
      0.45). Histories of each form of sex trafficking may relate differently to later
      HIV risk. Intervention with HIV-infected FSWs entering sex work as minors should
      be prioritized based on potential elevated risk of HIV transmission.

PMID- 23955658
TI  - Trends in HIV prevalence and HIV testing among young MSM: five United States
      cities, 1994-2011.
AB  - We examined trends in cross-sectional HIV prevalence (a surrogate for incidence)
      and past 12 month testing behavior among young men who have sex with men (MSM).
      The Young Men's Survey and the National HIV Behavioral Surveillance System
      conducted interviews and HIV testing among MSM recruited by venue-based sampling
      during 1994-2011. Using data from five cities, we determined whether interview
      year was associated with HIV prevalence and recent testing for MSM ages 18-22 and
      23-29 years, after adjusting for city, race/ethnicity, and education.
      Multivariable analysis demonstrated an overall increase in prevalence among MSM
      ages 23-29 years, driven by an increase in Baltimore. There was no change in HIV
      prevalence among MSM ages 18-22 years overall, although prevalence increased in
      Baltimore. HIV testing increased significantly for both age groups. Gains in HIV
      testing are encouraging, but increasing prevalence among young MSM in Baltimore
      suggests increasing incidence and the need for additional efforts for this
      population. 

PMID- 23955659
TI  - Whoonga: potential recreational use of HIV antiretroviral medication in South
      Africa.
AB  - Whoonga is a drug cocktail in South Africa rumored to contain illicit drugs and
      HIV antiretroviral (ARV) medication. Although its use may adversely impact
      adherence to HIV treatment and may have the potential to generate ARV resistance,
      there is a paucity of research characterizing whoonga. We learned of whoonga
      during semi-structured interviews about substance abuse and HIV risk at "club
      events" known as inkwaris in an urban township of Durban, South Africa. Whoonga
      was an emerging theme spontaneously identified as a problem for the community by
      17 out of 22 informants. Perceptions of whoonga suggest that it is highly
      addictive, contains ARVs (notably efavirenz), is used by individuals as young as
      14, and poses a threat to the health and safety of those who use it, including
      increasing the risk of HIV infection. Our informants provide preliminary evidence
      of the dangers of whoonga and reinforce the need for further study. 

PMID- 23955660
TI  - Predictors of non-adherence to clinical follow-up among patients participating in
      a randomized trial of pharmaceutical care intervention in HIV-positive adults in
      Southern Brazil.
AB  - Pharmaceutical care (PC) has been shown to improve adherence to therapeutic
      interventions as well as improve clinical outcomes. We assessed the predictors of
      non-adherence to clinical follow-up (i.e., not attending three scheduled routine
      clinical visits over a 1 year period) among patients who participated in a
      clinical trial of PC intervention on adherence to HIV antiretroviral therapy
      uptake (the PC-HIV trial). A total of 332 patients participated: median age was
      39 years, 63 % were male, 76 % had CD4 count >=200 cells/mm3, and 52 % had
      undetectable viral load. About half, 52.7 %, were non-adherent to clinical follow
      up. Identified risk factors for non-adherence were male gender, age <40 years,
      and being in the trial's "control" group (adjusted odds ratio [AOR] 1.67, 95 % CI
      1.05-2.66; AOR 2.21, 95 % CI 1.42-3.47; AOR 1.67, 95 % CI 1.07-2.61,
      respectively). Younger, male patients may benefit from interventions such as PC,
      which facilitates engagement in care. 

PMID- 23955662
TI  - Characterization and assembly of a GFP-tagged cylindriform silk into hexameric
      complexes.
AB  - Spider silk has been studied extensively for its attractive mechanical properties
      and potential applications in medicine and industry. The production of spider
      silk, however, has been lagging behind for lack of suitable systems. Our approach
      focuses on solving the production of spider silk by designing, expressing,
      purifying and characterizing the silk from cylindriform glands. We show that the
      cylindriform silk protein, in contrast to the commonly used dragline silk
      protein, is fully folded and stable in solution. With the help of GFP as a fusion
      tag we enhanced the expression of the silk protein in Escherichia coli and could
      optimize the downstream processing. Secondary structures analysis by circular
      dichroism and FTIR shows that the GFP-silk fusion protein is predominantly alpha
      helical, and that pH can trigger a alpha- to beta-transition resulting in
      aggregation. Structural analysis by small angle X-ray scattering suggests that
      the GFP-Silk exists in the form of a hexamer in solution.

PMID- 23955663
TI  - Toxicodynamics of copper and cadmium in Folsomia candida exposed to simulated
      soil solutions.
AB  - To improve our understanding of metal bioavailability to soil-living
      invertebrates, the effect of porewater composition on the toxicodynamics of
      copper and cadmium in Folsomia candida (Collembola) was investigated. Assuming
      that porewater is the main exposure route, F. candida was exposed to simulated
      soil solutions of different composition. Toxicity of copper was slightly lower in
      a calcium-only solution than in a multication solution. With increasing copper
      concentrations from 0.005 mM to 1.37 mM, internal copper concentrations similarly
      increased in both exposure solutions, suggesting that a single cation nutrient
      solution is suitable for testing F. candida. In the second experiment, animals
      were exposed for 7 d to copper and cadmium in simplified soil solutions with
      different calcium (0.2 mM, 0.8 mM, 3.2 mM, 12.8 mM) and pH (5.0, 6.0, 7.0)
      levels. The median lethal concentration (LC50) values decreased with time in both
      the calcium and pH series. A hormetic-type effect was observed for copper in the
      second test, as well as in the calcium-only solution in the first experiment.
      Because of stronger hormesis, LC50s for copper were higher at lower calcium
      concentrations. For cadmium, LC50 values were higher at higher calcium
      concentrations, suggesting competition of calcium with the free cadmium ion.
      Toxicity of cadmium increased with decreasing pH, while copper was more toxic at
      intermediate pH. The results show that a toxicodynamics approach can help to
      improve the interpretation of metal toxicity to soil invertebrates, taking into
      account soil solution properties.

PMID- 23955661
TI  - Rapid effector function of memory CD8+ T cells requires an immediate-early
      glycolytic switch.
AB  - Antigen-experienced memory T cells acquire effector function with innate-like
      kinetics; however, the metabolic requirements of these cells are unknown. Here we
      show that rapid interferon-gamma (IFN-gamma) production of effector memory (EM)
      CD8(+) T cells, activated through stimulation mediated by the T cell antigen
      receptor (TCR) and the costimulatory receptor CD28 or through cognate
      interactions, was linked to increased glycolytic flux. EM CD8(+) T cells
      exhibited more glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity at early
      time points, before proliferation commenced, than did naive cells activated under
      similar conditions. CD28 signaling via the serine-threonine kinase Akt and the
      metabolic-checkpoint kinase mTORC2 was needed to sustain TCR-mediated immediate
      early glycolysis. Unlike glycolysis in proliferating cells, immediate-early
      glycolysis in memory CD8(+) T cells was rapamycin insensitive. Thus, CD8(+)
      memory T cells have an Akt-dependent 'imprinted' glycolytic potential that is
      required for efficient immediate-early IFN-gamma recall responses. 

PMID- 23955664
TI  - Role of metabolic surgery in less obese or non-obese subjects with type 2
      diabetes: influence over cardiovascular events.
AB  - Bariatric surgery was initially developed as a tool for weight reduction only,
      but it is gaining increasing popularity because of its remarkable effect on
      glucose metabolism in morbidly obese and less obese patients. Recent publications
      have shown the good results of metabolic surgery, creating a new field of
      clinical research that is currently overflowing in the medical community with
      outstanding high-quality data. In morbidly obese population, there is compelling
      data on long term cardiovascular risk reduction and mortality, coming from
      longitudinal prospective studies and systematic reviews. Numbers range from 33 to
      92% of decrease in fatal and nonfatal cardiovascular events . In low body mass
      index (BMI) diabetics, there is an increasing number of reported good outcomes
      after metabolic surgery with the aim to treat type 2 diabetes (T2DM). There is
      scarce information on cardiovascular outcomes in non-morbidly obese subjects, but
      the extraordinary glucose, lipid and blood pressure control in the published
      series are suggesting good long-term effects on cardiovascular risk profile and
      mortality. The papers review was comprehensive, including the available
      randomized controlled trials, long-term prospective series and systematic
      reviews.

PMID- 23955665
TI  - Diabetes remission following metabolic surgery: is GLP-1 the culprit?
AB  - The parallel occurrence of improved glucose tolerance and increased glucagon-like
      peptide 1 (GLP-1) response to meal intake following metabolic surgery (MS)
      demonstrated in several studies has led to the notion that GLP-1 is the culprit
      for the impressive rates of remission of type 2 diabetes mellitus (T2DM)
      following MS. In this article, we critically review current evidence supporting
      this view. Recent studies specifically designed to elucidate a causative role of
      GLP-1 in the antidiabetic effects of MS call into question GLP-1 as a key player
      for T2DM outcome following MS procedures such as Roux-en-Y gastric bypass and
      sleeve gastrectomy in morbidly obese subjects. Whether GLP-1 plays a more
      prominent role in the remission of T2DM following MS in subjects with moderate
      obesity warrants further studies. Appraisal of the mechanisms involved in the
      amelioration of hyperglycemia following MS is a priority, as it could help in the
      battle against the current combined epidemics of obesity and T2DM. 

PMID- 23955666
TI  - Biofilm and planktonic lifestyles differently support the resistance of the
      desert cyanobacterium Chroococcidiopsis under space and Martian simulations.
AB  - When Chroococcidiopsis sp. strain CCMEE 057 from the Sinai Desert and strain
      CCMEE 029 from the Negev Desert were exposed to space and Martian simulations in
      the dried status as biofilms or multilayered planktonic samples, the biofilms
      exhibited an enhanced rate of survival. Compared to strain CCMEE 029, biofilms of
      strain CCME 057 better tolerated UV polychromatic radiation (5 * 10(5) kJ/m(2)
      attenuated with a 0.1% neutral density filter) combined with space vacuum or
      Martian atmosphere of 780 Pa. CCMEE 029, on the other hand, failed to survive UV
      polychromatic doses higher than 1.5 * 10(3) kJ/m(2). The induced damage to
      genomic DNA, plasma membranes and photosynthetic apparatus was quantified and
      visualized by means of PCR-based assays and CLSM imaging. Planktonic samples of
      both strains accumulated a higher amount of damage than did the biofilms after
      exposure to each simulation; CLSM imaging showed that photosynthetic pigment
      bleaching, DNA fragmentation and damaged plasma membranes occurred in the top 3-4
      cell layers of both biofilms and of multilayered planktonic samples. Differences
      in the EPS composition were revealed by molecular probe staining as contributing
      to the enhanced endurance of biofilms compared to that of planktonic samples. Our
      results suggest that compared to strain CCMEE 029, biofilms of strain CCMEE 057
      might better tolerate 1 year's exposure in space during the next EXPOSE-R2
      mission.

PMID- 23955667
TI  - Reduction of nitrite and nitrate on nano-dimensioned FeS.
AB  - The reaction of nitrite (NO2(-)) and nitrate (NO3(-)) on nanometer-sized FeS
      particles was investigated in alkaline (initial pH = 10.3) solutions at reaction
      temperatures of 22, 70, and 120  degrees C using in situ attenuated total
      reflection Fourier transform infrared spectroscopy (ATR-FTIR) and fluorescence
      spectroscopy that allowed an analysis of adsorbate complexation on the FeS and
      reaction product in the aqueous phase, respectively. ATR-FTIR showed that NO was
      a surface-bound intermediate on FeS during its exposure to NO2(-) at all three
      reaction temperatures. Ammonia/ammonium (NH3/NH4(+)) product was also produced
      when FeS was exposed to NO2(-) at the 70  degrees C and 120  degrees C reaction
      temperatures. Activation of NO3(-) to form surface-bound NO was experimentally
      observed to occur at 120  degrees C on FeS, but not at the lower reaction
      temperatures. Furthermore, NH3/NH4(+) product in the aqueous phase was only
      present during the reaction of FeS with NO3(-) at the highest temperature used in
      this study.

PMID- 23955669
TI  - Structure of chromatin in spermatozoa.
AB  - The specialized structure of the sperm chromatin has a dual function - first to
      protect the DNA from damage during storage and transport to the oocyte, and then
      to enable a rapid and complete unpacking of the undamaged paternal genome in the
      ooplasm. It is evident that zinc has a pivotal role in maintaining the structural
      stability and in enabling a rapid decondensation at the appropriate time. It is
      important for the sperm chromatin structure that the spermatozoa are ejaculated
      together with the zinc-rich prostatic secretion. Early exposure to zinc-binding
      seminal vesicular fluid can deplete the sperm chromatin of zinc and most likely
      induce surplus formation of disulfide bridges, likely to cause incomplete and
      delayed decondensation of the sperm chromatin in the oocyte. A premature decrease
      in sperm chromatin structure stability is likely to increase the risk for damage
      to the DNA due to increased access to the genome for DNA damaging compounds. The
      status of the sperm chromatin structure can vary in vitro depending on the
      exposure to zinc-depleting conditions when spermatozoa are stored in semen after
      ejaculation. When sperm DNA damage tests are evaluated and validated, it is
      therefore essential to also take into account the dynamics of zinc-dependent and
      zinc-independent sperm chromatin stability. 

PMID- 23955668
TI  - A rare malignancy of the parotid gland in a 13-year-old Taiwanese boy: case
      report of a mammary analogue secretory carcinoma of the salivary gland with
      molecular study.
AB  - Mammary analogue secretory carcinoma (MASC) is a recently described malignancy of
      the salivary glands characterized by an ETV6-NTRK3 (EN) fusion gene.
      Morphologically, MASC is sometimes difficult to distinguish from acinic cell
      carcinoma. Consequently, identifying the chromosomal translocation is essential
      for diagnosis. We present a case of parotid gland MASC in a 13-year-old boy. To
      the best of our knowledge, this is the youngest case reported in the literature.
      Histologic evaluation showed a tumor composed of microcysts, tubular structures,
      solid nests, or papillary architecture, with secretions within the lumens of the
      cysts or tubules. Immunohistochemically, tumor cells showed diffuse positive
      staining of S-100 protein, cytokeratin 19, and vimentin. ETV6 rearrangement was
      detected by fluorescence in situ hybridization and EN fusion transcripts were
      verified by reverse transcription (RT-PCR) assay. 

PMID- 23955670
TI  - Genomic changes in spermatozoa of the aging male.
AB  - Modern society is witnessing a widespread tendency to postpone parenthood due to
      a number of socioeconomic factors. This ever-increasing trend relates to both
      women and men and raises many concerns about the risks and consequences lying
      beneath the natural process of aging. The negative influence of the advanced
      maternal age has been thoroughly demonstrated, while the paternal age has
      attracted comparatively less attention. A problematic issue of defining whether
      advanced paternal age can be considered an independent risk factor, not only for
      a man's fertility but also for the offspring's health, is represented by the
      difficulty, linked to reproductive studies, in characterizing the impact of
      maternal and paternal age, separately. Researchers are now trying to overcome
      this obstacle by directly analyzing the male germ cell, and emerging data prove
      this sperm-specific approach to be a valid tool for providing novel insights on
      the effects of aging on the spermatozoa and, thus, on the reproductive outcome of
      an aging male. The purpose of this chapter is to summarize most of what is known
      about the relationship between male aging and changes in the spermatozoa, giving
      special focus on the events occurring with age at the genomic level. 

PMID- 23955671
TI  - Chromosomal aberrations and aneuploidies of spermatozoa.
AB  - Chromosomal abnormalities are relevant causes of human infertility, affecting 2 
      14 % of infertile males. Patients with seminal anomalies could be affected by
      improper meiotic recombination and increased sperm chromosome aneuploidy. Since
      the transmission of a haploid chromosomal asset is fundamental for embryo
      vitality and development, the study of sperm chromosomes has become fundamental
      because intracytoplasmic sperm injection allows fertilization in cases of severe
      male infertility.In this chapter we summarize the data on the incidence of sperm
      aneuploidy, detected by fluorescence in situ hybridization (FISH), in infertile
      men with normal or abnormal karyotype. The possibility of reducing sperm
      chromosomal imbalance is also reported.Among control males, the lowest aneuploidy
      rate was detected (range: 0.09 -0.14 % for autosomes; 0.04 -0.10 % for
      gonosomes). In infertile patients with normal karyotype, the severity of semen
      alteration is correlated with the frequency of aneuploidy, particularly for X and
      Y chromosomes. Among patients with abnormal karyotype, 47,XXY and 47,XYY carriers
      showed a high variability of sperm aneuploidy both for gonosomes and autosomes.
      In Robertsonian translocation carriers, the increase in aneuploidy rate was
      particularly evident for total sex disomy, and resulted mainly from
      interchromosomal effect (ICE). In reciprocal translocation carriers, a high
      percentage of unbalanced sperm (approximately 50 %) was detected, perhaps mostly
      related to ICE.Sperm chromosomal constitution could be analyzed to obtain more
      accurate information about the causes of male infertility. It would be worthwhile
      to evaluate the benefits of a therapy with recombinant Follicle Stimulating
      Hormone (rFSH) on sperm chromosome segregation in selected infertile males. 

PMID- 23955672
TI  - The sperm epigenome: implications for the embryo.
AB  - Recent advances, including the human genome project and numerous studies of
      cancer and other diseases, have shown that the genetic code is not simply limited
      to the sequence of the four bases of DNA but also includes epigenetic
      programming, heritable changes that affect gene expression [Riggs A, Martinssen
      R, Russo V (2007) Introduction. In: Riggs A, Martinssen R, Russo V (eds)
      Epigenetics mechanisms of gene regulation. Cold Spring Harbor Press, New York].
      The science of epigenetics is important in understanding many diseases and
      biological processes, including in identifying the causes of disease and better
      understanding the mechanisms by which the environment can affect gene expression
      [Carrell Fertil Steril 97 (2):267-274, 2012]. This chapter will focus on the
      epigenome of sperm and particularly highlight the potential role of the sperm
      epigenome in embryogenesis.The sperm epigenome is unique and highly specialized
      because of the unique nature and function of sperm and because of the diverse
      requirements for successful fertilization. Due to the need for motility, sperm
      chromatin must be compacted and highly organized. During spermiogenesis the
      chromatin is packaged tightly into the sperm head by the replacement of most
      histones with protamines. This allows for protection of the DNA from the hostile
      environment in the female reproductive tract. Remaining histones can have
      chemical modifications to the tails of the protein that either facilitate or
      repress gene transcription. Sperm, like embryonic stem cells, have a unique
      pattern of histone modifications that includes both activating and silencing
      marks in the promoters of genes associated with development. These bivalent
      marks, along with DNA hypomethylation, comprise a unique state in which the key
      genes are "poised" for possible activation in embryogenesis. Sperm epigenetic
      abnormalities have been linked with multiple diseases including male factor
      infertility and poor embryogenesis. 

PMID- 23955673
TI  - Environmental epigenetics and effects on male fertility.
AB  - Environmental exposures to factors such as toxicants or nutrition can have
      impacts on testis biology and male fertility. The ability of these factors to
      influence epigenetic mechanisms in early life exposures or from ancestral
      exposures will be reviewed. A growing number of examples suggest environmental
      epigenetics will be a critical factor to consider in male reproduction. 

PMID- 23955674
TI  - Protamine alterations in human spermatozoa.
AB  - Protamines are the major nuclear proteins in sperm cells, having a crucial role
      in the correct packaging of the paternal DNA. The fact that protamine
      haploinsufficiency in mice resulted in abnormal chromatin packaging and male
      infertility suggested that the protamines could also be important candidates in
      explaining some of the idiopathic male infertility cases in humans. The first
      clinical studies focused on analyzing protamines at the protein level. Various
      studies have found the presence of an altered amount of protamines in some
      infertile patients, in contrast to the normal situation in fertile individuals
      where the two protamines, protamine 1 and protamine 2, are both present in
      approximately equal quantities. Subsequently, the protamine genes were the
      subject of various mutational genetic screening studies in search of variants
      that could be associated with deregulation in the protamine expression observed.
      The results of these protamine mutational studies showed that the presence of
      high penetrant mutations is a very rare cause of male infertility. However, some
      variants and some haplotypes described may behave as risk factors for male
      infertility. More recently, the presence of RNA in the mature sperm cell has also
      been investigated. The present chapter will introduce the basic aspects of
      protamine evolution and function and review the various articles published to
      date on the relationship between the protamines studied at the DNA, RNA, and
      protein levels and male infertility. 

PMID- 23955675
TI  - Sperm DNA fragmentation and base oxidation.
AB  - Sperm DNA damage has been shown to be a valuable diagnostic and prognostic
      biomarker for male infertility and assisted reproductive treatment (ART) outcome.
      It is linked to every fertility checkpoint from reduced fertilization rates,
      lower embryo quality and pregnancy rates to higher rates of spontaneous
      miscarriage and childhood diseases. It is more robust than conventional semen
      parameters.The aim of this chapter is to provide an overview of current
      laboratory tests and relationships between sperm DNA damage and clinical
      outcomes. The conclusion is that sperm DNA damage is an important indicator of
      semen quality, and its routine use in the fertility clinic would improve ART
      success rates. 

PMID- 23955677
TI  - Sperm cryopreservation: effects on chromatin structure.
AB  - Cryopreservation is a technique that can keep sperm alive indefinitely, enabling
      the conservation of male fertility. It involves the cooling of semen samples and
      their storage at -196 degrees C in liquid nitrogen. At this temperature all
      metabolic processes are arrested. Sperm cryopreservation is of fundamental
      importance for patients undergoing medical or surgical treatments that could
      induce sterility, such as cancer patients about to undergo genotoxic chemotherapy
      or radiotherapy, as it offers these patients not only the hope of future
      fertility but also psychological support in dealing with the various stages of
      the treatment protocols.Despite its importance for assisted reproduction
      technology (ART) and its success in terms of babies born, this procedure can
      cause cell damage and impaired sperm function. Various studies have evaluated the
      impact of cryopreservation on chromatin structure, albeit with contradictory
      results. Some, but not all, authors found significant sperm DNA damage after
      cryopreservation. However, studies attempting to explain the mechanisms involved
      in the aetiology of cryopreservation-induced DNA damage are still limited. Some
      reported an increase in sperm with activated caspases after cryopreservation,
      while others found an increase in the percentage of oxidative DNA damage. There
      is still little - and contradictory - information on the mechanism of the
      generation of DNA fragmentation after cryopreservation. More studies are needed
      to establish the true importance of such damage, especially to improve the
      results of ART.

PMID- 23955678
TI  - Sperm selection: effect on sperm DNA quality.
AB  - The selection of spermatozoa without DNA fragmentation and chromosomal diseases
      prior to assisted reproductive techniques helps to optimize the outcome of the
      treatment; in particular, sperm selection prior to in vitro fertilization (IVF)
      or intracytoplasmic sperm injection (ICSI) is crucial. In fact, although ICSI has
      been successfully and safely applied worldwide for almost 20 years, at the
      present time we have no real knowledge regarding the hypothetical long-term side
      effects on ICSI adults, given the increased likelihood of spermatozoa with
      defective nuclear content fertilizing oocytes.In the case of DNA damage, the
      basal sperm DNA fragmentation rate can be significantly reduced by some sperm
      processing procedures that improve the percentage of spermatozoa with normal
      chromatin structure by filtering out DNA-damaged spermatozoa. After this first
      step, new advances in micromanipulation can be performed to choose the "ideal"
      mature spermatozoa for ICSI, reducing potential damage to the gametes. In fact,
      it is possible to prevent fertilization by DNA-damaged and chromosomal-unbalanced
      spermatozoa by selecting ICSI sperm by maturation markers such as hyaluronic acid
      or other zona pellucida receptors. Furthermore, novel noninvasive imaging
      techniques can be valid tools for helping in the morphological selection of ICSI
      spermatozoa. 

PMID- 23955676
TI  - Iatrogenic genetic damage of spermatozoa.
AB  - Various factors that negatively influence male fertility can affect sperm
      morphology and physiology. Many studies on humans and animals suggest that both
      radiation and chemotherapy alter the sperm chromatin, inducing significant damage
      to sperm DNA, and decrease the level of protamination, thereby altering DNA
      compaction. Spermatozoa from cancer survivors are affected by chemotherapy even
      years after the end of treatment. We are exposed to various toxicants present in
      the environment (e.g., products of air pollution, pesticides, and plasticizers)
      whose impact on human male reproduction has not yet been established.This chapter
      aims to update our knowledge on how the sperm chromatin structure is modified by
      external agents and to describe the different strategies available to better
      study this complex structure in infertile men. 

PMID- 23955679
TI  - Effect of antioxidants on sperm genetic damage.
AB  - According to worldwide statistics, between one in four and one in five couples
      have fertility problems. These problems are equally distributed between males and
      females. Modern lifestyle has obviously increased these problems: endocrine
      disrupting chemicals, such as plastic polymer catalysts, alkylphenols, phthalates
      and so on, and cosmetic additives seem to be strongly involved in this fertility
      problem. Many of these compounds increase oxidative stress (OS) and thus impair
      spermatogenesis. The oocyte has only a finite capacity, decreasing with maternal
      age, to repair sperm-borne decays. To decrease this DNA repair burden, reducing
      the sperm DNA damages linked to OS is tempting. Antioxidant vitamins are often
      given haphazardly; they are not very efficient and potentially detrimental. A
      detailed analysis of the sperm nucleus is mandatory (DNA fragmentation or lack of
      nuclear condensation) prior to any treatment. Here we discuss new concepts in OS
      and the corresponding therapeutic approaches. 

PMID- 23955680
TI  - Minimally invasive sacrospinous ligament suspension: perioperative morbidity and
      review of the literature.

PMID- 23955681
TI  - Thermodynamically destabilized hydride formation in "bulk" Mg-AlTi multilayers
      for hydrogen storage.
AB  - Thermodynamic destabilization of MgH2 formation through interfacial interactions
      in free-standing Mg-AlTi multilayers of overall "bulk" (0.5 MUm) dimensions with
      a hydrogen capacity of up to 5.5 wt% is demonstrated. The interfacial energies of
      Mg-AlTi and Mg-Ti (examined as a baseline) are calculated to be 0.81 and 0.44 J
      m(-2). The enhanced interfacial energy of AlTi opens the possibility of creating
      ultrathin alloy interlayers that provide further thermodynamic improvements in
      metal hydrides. 

PMID- 23955682
TI  - Activation of local and systemic anti-tumor immune responses by ablation of solid
      tumors with intratumoral electrochemical or alpha radiation treatments.
AB  - Cancer, the most devastating chronic disease affecting humankind, is treated
      primarily by surgery, chemotherapy, and radiation therapy. Surgery and
      radiotherapy are mainly used for debulking the primary tumor, while chemotherapy
      is the most efficient anti-metastatic treatment. To control better metastatic
      cancer, the host immune system should be stimulated. Yet, successful specific
      stimulation of the immune system against tumors was seldom achieved even in
      antigenic tumors. Our working hypothesis is that aggressive in situ tumor
      ablation can release tumor antigens and danger signals, which will enhance anti
      tumor T cell responses resulting in the destruction of residual malignant cells
      in primary tumors and distant metastases. We developed two efficient in situ
      ablation treatments for solid cancer, which can be used to destroy the primary
      tumors and stimulate anti-tumor immune responses. The first treatment,
      electrochemical ablation, is applied through intratumoral electrodes, which
      deliver unipolar-pulsed electric currents. The second treatment, diffusing alpha
      emitters radiation therapy (DaRT), is based on intratumoral (224)Ra-loaded
      wire(s) that release by recoil its daughter atoms. These short-lived alpha
      emitting atoms spread in the tumor and spray it with lethal alpha particles. It
      was confirmed that these treatments effectively destroy various malignant animal
      and human primary solid tumors. As a consequence of such tumor ablation, tumor
      derived antigenic material was released and provoked systemic T cell-dependent
      anti-tumor immunological reactions. These reactions conferred protection against
      a secondary tumor challenge and destroyed remaining malignant cells in the
      primary tumor as well as in distant metastases. Such anti-tumor immune responses
      could be further amplified by the immune adjuvant, CpG. Electrochemical ablation
      or DaRT together with chemotherapy and immunostimulatory agents can serve as
      treatment protocols for solid metastatic tumors and can be applied instead of or
      in combination with surgery. 

PMID- 23955683
TI  - Reduced expression of NGEP is associated with high-grade prostate cancers: a
      tissue microarray analysis.
AB  - New gene expressed in prostate (NGEP) is a newly diagnosed prostate-specific gene
      that is expressed only in normal prostate and prostate cancer cells. Discovery of
      tissue-specific markers may promote the development of novel targets for
      immunotherapy of prostate cancer. In the present study, the staining pattern and
      clinical significance of NGEP were evaluated in a series of prostate tissues
      composed of 123 prostate cancer, 19 high-grade prostatic intraepithelial
      neoplasia and 44 samples of benign prostate tissue included in tissue microarrays
      using immunohistochemistry. Our study demonstrated that NGEP localized mainly in
      the apical and lateral membranes and was also partially distributed in the
      cytoplasm of epithelial cells of normal prostate tissue. All of the examined
      prostate tissues expressed NGEP with a variety of intensities; the level of
      expression was significantly more in the benign prostate tissues compared to
      malignant prostate samples (P value <0.001). Among prostate adenocarcinoma
      samples, a significant and inverse correlation was observed between the intensity
      of NGEP expression and increased Gleason score (P = 0.007). Taken together, we
      found that NGEP protein is widely expressed in low-grade to high-grade prostate
      adenocarcinomas as well as benign prostate tissues, and the intensity of
      expression is inversely proportional to the level of malignancy. NGEP could be an
      attractive target for immune-based therapy of prostate cancer patients as an
      alternative to the conventional therapies particularly in indolent patients.

PMID- 23955684
TI  - Lack of association of MTHFR rs1801133 polymorphism and CTCFL mutations with
      sperm methylation errors in infertile patients.
AB  - PURPOSE: To find out whether the MTHFR rs1801133 polymorphism is a risk factor
      for male infertility in the Spanish population. To determine if a pattern of
      sperm DNA hypomethylation at the paternally imprinted loci H19-ICR and/or IG-DMR
      is related to the MTHFR rs1801133 polymorphism and/or CTCFL mutations. METHODS:
      One hundred and seven samples from individuals who sought consultation for
      fertility problems and twenty-five semen samples from sperm donors were analyzed.
      The MTHFR rs1801133 SNP was analyzed in all samples by the PCR-RFLP method. We
      compared the distribution of the genotypes between control and infertile
      populations and among the groups of patients with altered seminal parameters. In
      those patients with the most severe hypomethylation pattern (n = 12) we also
      analyzed the CTCFL protein-coding exons by sequencing. RESULTS: There were no
      significant differences in the distribution of the genotypes among the control
      and infertile populations. Moreover, none of the genotypes were associated,
      neither to the characteristics of the seminogram, nor to the presence of sperm
      DNA hypomethylation. We did not identify frameshift, nonsense or missense
      mutations of the CTCFL gene. CONCLUSIONS: The MTHFR rs1801133 polymorphism is not
      associated with male infertility in the Spanish population. Neither the MTHFR
      polymorphism, nor CTCFL mutations explain a pattern of sperm hypomethylation at
      paternally imprinting loci.

PMID- 23955685
TI  - Thyroid stimulating hormone levels rise after assisted reproductive technology.
AB  - PURPOSE: The goal of this study was to determine whether high E2 levels after
      controlled ovarian hyperstimulation affect TSH. METHODS: Patients completing ART
      cycles between April-October 2010 were eligible for this cohort study. 180
      patients were recruited however those with known thyroid disease were excluded.
      The final analysis included 154 subjects. Blood was collected at each visit
      during the ART cycle as well as at the pregnancy test. Samples were frozen at -20
      degrees C and analyzed together for E2 and TSH using the same assay kit once all
      patients had completed their cycles. All participants were treated at the McGill
      University Health Center. A paired t-test was used to study the difference in TSH
      levels recorded at maximal and minimal Estradiol levels during ovarian
      stimulation. Multiple regression analysis was then used to determine if factors
      such as anti-thyroid antibodies and ovarian reserve measures affect this change
      in TSH. We used multiple imputation methods to account for missing data. RESULTS:
      As E2 levels rose from low to supra-physiologic levels during treatment, TSH
      levels also rose significantly. This increase was clinically significant by the
      time of pregnancy test. The factors that potentially affected the change in TSH
      were: male factor/tubal factor infertility, type of protocol used as well as the
      presence of thyroid antibodies. CONCLUSIONS: Although TSH increases during ART,
      this change only becomes clinically significant on the day of pregnancy test.
      Future studies should examine TSH changes specifically in certain "at-risk" sub
      groups such as those with antibodies and known thyroid disease.

PMID- 23955686
TI  - Beyond B-cell lymphomas: a case of optic nerve anaplastic large cell lymphoma in
      a HIV positive patient.

PMID- 23955687
TI  - Life threatening transmural arteritis of the internal carotid artery:
      reconstructive treatment with flow diverting stents.

PMID- 23955688
TI  - Cooperative catalysis of metal and O-H...O/sp3-C-H...O two-point hydrogen bonds
      in alcoholic solvents: Cu-catalyzed enantioselective direct alkynylation of
      aldehydes with terminal alkynes.
AB  - Catalyst-substrate hydrogen bonds in artificial catalysts usually occur in
      aprotic solvents, but not in protic solvents, in contrast to enzymatic catalysis.
      We report a case in which ligand-substrate hydrogen-bonding interactions
      cooperate with a transition-metal center in alcoholic solvents for
      enantioselective catalysis. Copper(I) complexes with prolinol-based hydroxy amino
      phosphane chiral ligands catalytically promoted the direct alkynylation of
      aldehydes with terminal alkynes in alcoholic solvents to afford nonracemic
      secondary propargylic alcohols with high enantioselectivities. Quantum-mechanical
      calculations of enantiodiscriminating transition states show the occurrence of a
      nonclassical sp(3)-C-H...O hydrogen bond as a secondary interaction between the
      ligand and substrate, which results in highly directional catalyst-substrate two
      point hydrogen bonding.

PMID- 23955689
TI  - A microfluidically cryocooled spiral microcoil with inductive coupling for MR
      microscopy.
AB  - Magnetic resonance (MR) microscopy typically employs microcoils for enhanced
      local signal-to-noise ratio (SNR). Planar (surface) microcoils, in particular,
      offer the potential to be configured into array elements as well as to enable the
      imaging of extremely small samples because of the uniformity and precision
      provided by microfabrication techniques. Microcoils, in general, however, are
      copper-loss dominant, and cryocooling methods have been successfully used to
      improve the SNR. Cryocooling of the matching network elements, in addition to the
      coil itself, has shown to provide the most improvement, but can be challenging
      with respect to cryostat requirements, cabling, and tuning. Here we present the
      development of a microfluidically cryocooled spiral microcoil with integrated
      microfabricated parallel plate capacitors, allowing for localized cryocooling of
      both the microcoil and the on-chip resonating capacitor to increase the SNR while
      keeping the sample-to-coil distance within the most sensitive imaging range of
      the microcoil. Inductive coupling was used instead of a direct transmission line
      connection to eliminate the physical connection between the microcoil and the
      tuning network so that a single cryocooling microfluidic channel could enclose
      both the microcoil and the on-chip capacitor with minimum loss in cooling
      capacity. Comparisons between the cooled and uncooled cases were made via Q
      factor measurements and agreed well with the theoretically achievable
      improvement: the cooled integrated capacitor coil with inductive coupling
      achieved a factor of 2.6 improvement in Q-factor over a reference coil
      conventionally matched and tuned with high- Q varactors and capacitively
      connected to the transmission line. 

PMID- 23955690
TI  - Unsupervised content classification based nonrigid registration of differently
      stained histology images.
AB  - Registration of histopathology images of consecutive tissue sections stained with
      different histochemical or immunohistochemical stains is an important step in a
      number of application areas, such as the investigation of the pathology of a
      disease, validation of MRI sequences against tissue images, multiscale physical
      modeling, etc. In each case, information from each stain needs to be spatially
      aligned and combined to ascertain physical or functional properties of the
      tissue. However, in addition to the gigabyte-size images and nonrigid distortions
      present in the tissue, a major challenge for registering differently stained
      histology image pairs is the dissimilar structural appearance due to different
      stains highlighting different substances in tissues. In this paper, we address
      this challenge by developing an unsupervised content classification method that
      generates multichannel probability images from a roughly aligned image pair. Each
      channel corresponds to one automatically identified content class. The
      probability images enhance the structural similarity between image pairs. By
      integrating the classification method into a multiresolution-block-matching-based
      nonrigid registration scheme (N. Roberts, D. Magee, Y. Song, K. Brabazon, M.
      Shires, D. Crellin, N. Orsi, P. Quirke, and D. Treanor, "Toward routine use of 3D
      histopathology as a research tool," Amer. J. Pathology, vol. 180, no. 5, 2012.),
      we improve the performance of registering multistained histology images.
      Evaluation was conducted on 77 histological image pairs taken from three liver
      specimens and one intervertebral disc specimen. In total, six types of
      histochemical stains were tested. We evaluated our method against the same
      registration method implemented without applying the classification algorithm
      (intensity-based registration) and the state-of-the-art mutual information based
      registration. Superior results are obtained with the proposed method. 

PMID- 23955691
TI  - An analytic tool for prediction of hemodynamic responses to vasopressors.
AB  - This paper presents a new analytic tool for automated control of vasopressor
      infusion, which uses measured changes in blood pressure to infer changes in the
      underlying cardiovascular system and then estimate dose-response relationships
      for the underlying cardinal cardiovascular parameters, i.e., those related to
      cardiac output (CO) and total peripheral resistance (TPR). Ultimately, blood
      pressure as a function of vasopressor dose is predicted based on the estimated
      underlying cardiovascular state by extrapolating the dose-response relationship.
      As well, this tool adapts to individual subjects with a minimum of individualized
      training data. In this report, proof-of-principle is provided using experimental
      epinephrine dose-response data from four different sets of subjects. Given two
      observations from different infusion rates, the analytic tool was able to
      accurately predict the groups' blood pressure, heart rate, TPR, stroke volume,
      and CO as a function of vasopressor dose levels: the root-mean-squared prediction
      error for the mean arterial pressure (MAP) was consistently smaller than 5% of
      the underlying MAP; the r(2) values for the TPR, stroke volume, and CO were
      consistently higher than 0.96; and the limits of agreement between actual versus
      predicted blood pressure (BP), TPR, stroke volume, and CO were consistently
      smaller than 8% of the respective underlying values. The proposed analytic tool
      may provide a meaningful step towards automated control of vasopressor therapy. 

PMID- 23955692
TI  - Airway tree segmentation in serial block-face cryomicrotome images of rat lungs.
AB  - A highly automated method for the segmentation of airways in the serial block
      face cryomicrotome images of rat lungs is presented. First, a point inside of the
      trachea is manually specified. Then, a set of candidate airway centerline points
      is automatically identified. By utilizing a novel path extraction method, a
      centerline path between the root of the airway tree and each point in the set of
      candidate centerline points is obtained. Local disturbances are robustly handled
      by a novel path extraction approach, which avoids the shortcut problem of
      standard minimum cost path algorithms. The union of all centerline paths is
      utilized to generate an initial airway tree structure, and a pruning algorithm is
      applied to automatically remove erroneous subtrees or branches. Finally, a
      surface segmentation method is used to obtain the airway lumen. The method was
      validated on five image volumes of Sprague-Dawley rats. Based on an expert
      generated independent standard, an assessment of airway identification and lumen
      segmentation performance was conducted. The average of airway detection
      sensitivity was 87.4% with a 95% confidence interval (CI) of (84.9, 88.6)%. A
      plot of sensitivity as a function of airway radius is provided. The combined
      estimate of airway detection specificity was 100% with a 95% CI of (99.4, 100)%.
      The average number and diameter of terminal airway branches was 1179 and 159 MUm,
      respectively. Segmentation results include airways up to 31 generations. The
      regression intercept and slope of airway radius measurements derived from final
      segmentations were estimated to be 7.22 MUm and 1.005, respectively. The
      developed approach enables the quantitative studies of physiology and lung
      diseases in rats, requiring detailed geometric airway models. 

PMID- 23955693
TI  - Electrokinetic Analysis of Cell Translocation in Low-Cost Microfluidic Cytometry
      for Tumor Cell Detection and Enumeration.
AB  - Conventional Coulter counters have been introduced as an important tool in
      biological cell assays since several decades ago. Recently, the emerging portable
      Coulter counter has demonstrated its merits in point of care diagnostics, such as
      on chip detection and enumeration of circulating tumor cells (CTC). The working
      principle is based on the cell translocation time and amplitude of electrical
      current change that the cell induces. In this paper, we provide an analysis of a
      Coulter counter that evaluates the hydrodynamic and electrokinetic properties of
      polystyrene microparticles in a microfluidic channel. The hydrodynamic force and
      electrokinetic force are concurrently analyzed to determine the translocation
      time and the electrical current pulses induced by the particles. Finally, we
      characterize the chip performance for CTC detection. The experimental results
      validate the numerical analysis of the microfluidic chip. The presented model can
      provide critical insight and guidance for developing micro-Coulter counter for
      point of care prognosis. 

PMID- 23955694
TI  - Nocturnal awakening and sleep efficiency estimation using unobtrusively measured
      ballistocardiogram.
AB  - Fragmented sleep due to frequent awakenings represents a major cause of impaired
      daytime performance and adverse health outcomes. Currently, the gold standard for
      studying and assessing sleep fragmentation is polysomnography (PSG). Here, we
      propose an alternative method for real-time detection of nocturnal awakening via
      ballistocardiography using an unobtrusive polyvinylidene fluoride (PVDF) film
      sensor on a bed mattress. From ballistocardiogram, heart rate and body movement
      information were extracted to develop an algorithm for classifying sleeping and
      awakening epochs. In total, ten normal subjects (mean age 38.7 +/- 14.6 years)
      and ten patients with obstructive sleep apnea (OSA) (mean age 44.2 +/- 16.5
      years) of varying symptom severity participated in this study. Our study detected
      awakening epochs with an average sensitivity of 85.3% and 85.2%, specificity of
      98.4% and 97.7%, accuracy of 97.4% and 96.5%, and Cohen's kappa coefficient of
      0.83 and 0.81 for normal subjects and OSA patients, respectively. Also, sleep
      efficiency was estimated using detected awakening epochs and then compared with
      PSG results. Mean absolute errors in sleep efficiency were 1.08% and 1.44% for
      normal subjects and OSA patients, respectively. The results presented here
      indicate that our suggested method could be reliably applied to real-time
      nocturnal awakening detection and sleep efficiency estimation. Furthermore, our
      method may ultimately be an effective tool for long-term, home monitoring of
      sleep-wake behavior. 

PMID- 23955695
TI  - EnerCage: a smart experimental arena with scalable architecture for behavioral
      experiments.
AB  - Wireless power, when coupled with miniaturized implantable electronics, has the
      potential to provide a solution to several challenges facing neuroscientists
      during basic and preclinical studies with freely behaving animals. The EnerCage
      system is one such solution as it allows for uninterrupted electrophysiology
      experiments over extended periods of time and vast experimental arenas, while
      eliminating the need for bulky battery payloads or tethering. It has a scalable
      array of overlapping planar spiral coils (PSCs) and three-axis magnetic sensors
      for focused wireless power transmission to devices on freely moving subjects. In
      this paper, we present the first fully functional EnerCage system, in which the
      number of PSC drivers and magnetic sensors was reduced to one-third of the number
      used in our previous design via multicoil coupling. The power transfer efficiency
      (PTE) has been improved to 5.6% at a 120 mm coupling distance and a 48.5 mm
      lateral misalignment (worst case) between the transmitter (Tx) array and receiver
      (Rx) coils. The new EnerCage system is equipped with an Ethernet backbone,
      further supporting its modular/scalable architecture, which, in turn, allows
      experimental arenas with arbitrary shapes and dimensions. A set of experiments on
      a freely behaving rat were conducted by continuously delivering 20 mW to the
      electronics in the animal headstage for more than one hour in a powered 3538
      cm(2) experimental area. 

PMID- 23955696
TI  - Robustness and accuracy of feature-based single image 2-D-3-D registration
      without correspondences for image-guided intervention.
AB  - 2-D-to-3-D registration is critical and fundamental in image-guided
      interventions. It could be achieved from single image using paired point
      correspondences between the object and the image. The common assumption that such
      correspondences can readily be established does not necessarily hold for image
      guided interventions. Intraoperative image clutter and an imperfect feature
      extraction method may introduce false detection and, due to the physics of X-ray
      imaging, the 2-D image point features may be indistinguishable from each other
      and/or obscured by anatomy causing false detection of the point features. These
      create difficulties in establishing correspondences between image features and 3
      D data points. In this paper, we propose an accurate, robust, and fast method to
      accomplish 2-D-3-D registration using a single image without the need for
      establishing paired correspondences in the presence of false detection. We
      formulate 2-D-3-D registration as a maximum likelihood estimation problem, which
      is then solved by coupling expectation maximization with particle swarm
      optimization. The proposed method was evaluated in a phantom and a cadaver study.
      In the phantom study, it achieved subdegree rotation errors and submillimeter in
      plane ( X- Y plane) translation errors. In both studies, it outperformed the
      state-of-the-art methods that do not use paired correspondences and achieved the
      same accuracy as a state-of-the-art global optimal method that uses correct
      paired correspondences. 

PMID- 23955700
TI  - Saccharopolyspora cavernae sp. nov., a novel actinomycete isolated from the
      Swallow Cave in Yunnan, south-west China.
AB  - A Gram-positive, aerobic, non-motile actinobacterial strain, designated YIM
      C01235(T), was isolated from a soil sample collected from the Swallow Cave,
      Yunnan province, south-west China. The isolate grew at 10-30  degrees C, pH 6.0
      9.0 and 0-8 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences
      revealed highest similarity to Saccharopolyspora gloriosae YIM 60513(T) (96.8 %),
      and lower 16S rRNA gene sequence similarities (95.1-96.7 %) with the other
      species of the genus Saccharopolyspora. The whole-cell hydrolysates contained
      meso-diaminopimelic acid (meso-DAP), arabinose and galactose. The polar lipids
      were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylmethylethanolamine, two unknown
      glycolipids, two unknown phospholipids and one polar lipid. MK-9(H4) was the
      predominant menaquinone. The major fatty acids were iso-C15:0, iso-C16:0, anteiso
      C15:0 and anteiso-C17:0. Mycolic acids were not detected. The genomic DNA G+C
      content was 69.1 mol%. These chemotaxonomic data, together with its morphological
      properties, were consistent with the assignment of strain YIM C01235(T) to the
      genus Saccharopolyspora. The results of physiological and biochemical tests
      allowed strain YIM C01235(T) to be differentiated phenotypically from all the
      recognized Saccharopolyspora species. On the basis of evidence from this
      polyphasic study, the novel species Saccharopolyspora cavernae sp. nov. is
      proposed. The type strain is YIM C01235(T) (=DSM 45825(T) = CCTCC AA 2012022(T)).

PMID- 23955701
TI  - Effect of beta3 adrenoceptor activation in the basolateral amygdala on ethanol
      seeking behaviors.
AB  - RATIONALE: The interaction between ethanol (EtOH) and anxiety plays an integral
      role in the development and maintenance of alcoholism. Many medications in pre
      clinical or clinical trials for the treatment of alcoholism share anxiolytic
      properties. However, these drugs typically have untoward side effects, such as
      sedation or impairment of motor function that may limit their clinical use. We
      have recently demonstrated that BRL 37344 (BRL), a selective beta3-adrenoceptor
      (AR) agonist, enhances a discrete population of GABAergic synapses in the
      basolateral amygdala (BLA) that mediates feed-forward inhibition from lateral
      paracapsular (LPC) GABAergic interneurons onto BLA pyramidal cells. Behavioral
      studies revealed that intra-BLA infusion of BRL significantly reduced measures of
      unconditioned anxiety-like behavior without locomotor depressant effects.
      OBJECTIVES: The present studies tested the effect of BRL (0.1, 0.5, or 1.0
      MUg/side) on EtOH self-administration using an intermittent access home cage two
      bottle choice procedure and limited access operant responding for EtOH or
      sucrose. RESULTS: Intra-BLA infusion of BRL did not reduce home cage,
      intermittent EtOH self-administration. However, using an operant procedure that
      permits the discrete assessment of appetitive (seeking) and consummatory measures
      of EtOH self-administration, BRL reduced measures of EtOH and sucrose seeking,
      but selectively reduced operant responding for EtOH during extinction probe
      trials. BRL had no effect on consummatory behaviors for EtOH or sucrose.
      CONCLUSIONS: Together, these data suggest that intra-BLA infusion of BRL
      significantly reduces motivation to seek EtOH and provide initial evidence that
      beta3-ARs and LPC GABAergic synapses may represent promising targets for the
      development of novel pharmacotherapies for the treatment of alcoholism.

PMID- 23955703
TI  - Electronic, magnetic and optical properties of Cu, Ag, Au-doped Si clusters.
AB  - The structural, optical and magnetic properties of Cu, Ag, Au-doped Si7 Clusters
      have been systematically investigated using density functional theory
      calculations. The global optimized structures of Cu, Ag, Au-doped Si clusters are
      predicted to have a lower HOMO-LUMO gap and higher magnetic moment. M-doping (M =
      Cu, Ag, Au) in Si cluster widens a range of adsorption wavelength, especially Au
      doping. The characteristics in electronic density of states (DOSs) show that C5v
      Si6Cu has a big asymmetrical spin-up and spin-down. The average atomic moment is
      0.428 mMUB per atom for the Si6Cu cluster with C5v symmetry, while the average
      paramagnetic moment is 0.143 mMUB per atom for other M-doped (M = Cu, Ag, Au) Si7
      clusters.

PMID- 23955702
TI  - Cortical glutathione levels in young people with bipolar disorder: a pilot study
      using magnetic resonance spectroscopy.
AB  - RATIONALE: Glutathione (GSH) is a key scavenger for cellular free radicals, and
      patients with bipolar disorder may have lowered GSH levels in plasma and in post
      mortem brain tissue. OBJECTIVES: The objective of the current study was to use
      magnetic resonance spectroscopy (MRS) to measure cortical GSH levels in young
      people with bipolar disorder to determine if lowered GSH might be a useful
      biomarker of vulnerability to the illness. METHODS: We studied 13 patients with
      DSM-IV bipolar disorder and 11 healthy age-matched controls using proton MRS in
      conjunction with the SPECIAL acquisition technique. Voxels were placed in
      prefrontal and occipital cortex. All patients were clinically euthymic at the
      time of study and unmedicated. GSH and other relevant neurometabolites were
      measured relative to creatinine. RESULTS: There was no difference in GSH levels
      between bipolar participants and controls in either prefrontal or occipital
      cortex. Similarly, participants showed no difference from controls in other
      measured cortical metabolites including gamma-aminobutyric acid, glutamate and N
      acetylaspartate. CONCLUSIONS: This pilot study suggests that levels of cortical
      GSH are unlikely to be a useful trait biomarker of bipolar disorder in young
      people with a history of relatively mild mood instability at an early stage of
      illness. Lowered GSH levels may be relevant to bipolar pathophysiology in more
      severely ill patients, particular those with significant current mood
      disturbance.

PMID- 23955704
TI  - International conference: Modeling & Design of Molecular Materials--MDMM 2012
      (September 10-14, 2012, Wroclaw, Poland).

PMID- 23955705
TI  - Nickel/zinc-catalyzed decarbonylative addition of anhydrides to alkynes: a DFT
      study.
AB  - Density functional theory (DFT) was used to investigate the nickel- or
      nickel(0)/zinc- catalyzed decarbonylative addition of phthalic anhydrides to
      alkynes. All intermediates and transition states were optimized completely at the
      B3LYP/6-31+G(d,p) level. Calculated results indicated that the decarbonylative
      addition of phthalic anhydrides to alkynes was exergonic, and the total free
      energy released was -87.6 kJ mol(-1). In the five-coordinated complexes M4a and
      M4b, the insertion reaction of alkynes into the Ni-C bond occurred prior to that
      into the Ni-O bond. The nickel(0)/zinc-catalyzed decarbonylative addition was
      much more dominant than the nickel-catalyzed one in whole catalytic
      decarbonylative addition. The reaction channel CA->M1'->T1'->M2'->T2'->M3a'->M4a'
      >T3a1'->M5a1' ->T4a1'->M6a'->P was the most favorable among all reaction pathways
      of the nickel- or nickel(0)/zinc- catalyzed decarbonylative addition of phthalic
      anhydrides to alkynes. And the alkyne insertion reaction was the rate-determining
      step for this channel. The additive ZnCl2 had a significant effect, and it might
      change greatly the electron and geometry structures of those intermediates and
      transition states. On the whole, the solvent effect decreased the free energy
      barriers.

PMID- 23955707
TI  - Effects of environmentally realistic daily temperature variation on pesticide
      toxicity to aquatic invertebrates.
AB  - The toxicity of several agricultural chemicals to aquatic invertebrates has been
      shown to be temperature-dependent, but the role of daily temperature variation
      has rarely been examined. The authors simulated a natural daily temperature
      pattern (a fluctuating cycle of 21  degrees C to 31  degrees C over a 24-h
      period) based on field-collected data from Southern High Plains wetlands (TX,
      USA) and conducted a series of experiments comparing responses from this exposure
      scenario to a constant exposure at 24 +/- 1  degrees C. Results indicate
      alterations in pesticide toxicity under the fluctuating temperature regime
      compared with that of the constant temperature exposure. There was a significant
      interaction of temperature regime and bifenthrin on Chironomus dilutus survival,
      and C. dilutus ash-free dry mass was lower in the fluctuating temperature
      treatment. The 10-d median lethal concentration (LC50) for Hyalella azteca
      exposed to chlorothalonil was lower under the fluctuating temperature regime
      compared with the constant temperature regime. For Daphnia magna exposed to
      malathion, the main effects of temperature regime and malathion were observed on
      cholinesterase activity. The present study demonstrates how environmentally
      relevant daily temperature variation influences contaminant effects on aquatic
      invertebrates.

PMID- 23955709
TI  - Impact of vitamin A supplementation on RAR gene expression in multiple sclerosis
      patients.
AB  - Vitamin A and its derivatives have been shown to modulate the immune system via
      retinoic acid receptor (RAR). This study explored the impact of retinyl palmitate
      supplementation on RAR subtype gene expression in peripheral blood mononuclear
      cells (PBMCs) in multiple sclerosis (MS) patients. The study designed as a double
      blind randomized clinical trial in which relapsing remitting multiple sclerosis
      patients were evaluated. Both groups received one capsule 50,000 IU vitamin D3
      per 2 weeks and one intramuscular injection interferon beta-1a per week. The
      intervention group received one 25,000 IU retinyl palmitate capsule daily for 6
      months and the placebo group received one placebo capsule daily. The PBMCs were
      isolated from participants and the expression level changes of RAR-alpha and RAR
      gamma genes were determined by real-time PCR. After supplementation, in the
      intervention group, the RAR-alpha gene expression level was significantly
      decreased compared to the placebo group (p = 0.03); however, the expression of
      RAR-gamma gene did not significantly change (p = 0.10). These results show that
      vitamin A supplementation can significantly downregulate the expression of RAR
      alpha gene in PBMCs of MS patients that suggest the presence of in vivo
      regulatory mechanisms for the action of vitamin A on the immune system.

PMID- 23955710
TI  - Inducible expression of p50 from TMV for increased resistance to bacterial crown
      gall disease in tobacco.
AB  - The dominant tobacco mosaic virus (TMV) resistance gene N induces a
      hypersensitive response upon TMV infection and protects tobacco against systemic
      spread of the virus. It has been proposed to change disease resistance
      specificity by reprogramming the expression of resistance genes or their
      corresponding avirulence genes. To reprogramme the resistance response of N
      towards bacterial pathogens, the helicase domain (p50) of the TMV replicase, the
      avirulence gene of N, was linked to synthetic promoters 4D and 2S2D harbouring
      elicitor-responsive cis-elements. These promoter::p50 constructs induce local
      necrotic lesions on NN tobacco plants in an Agrobacterium tumefaciens
      infiltration assay. A tobacco genotype void of N (nn) was transformed with the
      promoter::p50 constructs and subsequently crossed to NN plants. Nn F1 offspring
      selected for the T-DNA develop normally under sterile conditions. After transfer
      to soil, some of the F1 plants expressing the 2S2D::p50 constructs develop
      spontaneous necrosis. Transgenic Nn F1 plants with 4D::p50 and 2S2D::p50
      expressing constructs upregulate p50 transcription and induce local necrotic
      lesions in an A. tumefaciens infiltration assay. When leaves and stems of Nn F1
      offspring harbouring promoter::p50 constructs are infected with oncogenic A.
      tumefaciens C58, transgenic lines harbouring the 2S2D::p50 construct induce
      necrosis and completely lack tumor development. These results demonstrate a
      successful reprogramming of the viral N gene response against bacterial crown
      gall disease and highlight the importance of achieving tight regulation of
      avirulence gene expression and the control of necrosis in the presence of the
      corresponding resistance gene.

PMID- 23955711
TI  - Inhibition of p300 impairs Foxp3+ T regulatory cell function and promotes
      antitumor immunity.
AB  - Forkhead box P3 (Foxp3)(+) T regulatory (T(reg)) cells maintain immune
      homeostasis and limit autoimmunity but can also curtail host immune responses to
      various types of tumors. Foxp3(+) T(reg) cells are therefore considered promising
      targets to enhance antitumor immunity, and approaches for their therapeutic
      modulation are being developed. However, although studies showing that
      experimentally depleting Foxp3(+) T(reg) cells can enhance antitumor responses
      provide proof of principle, these studies lack clear translational potential and
      have various shortcomings. Histone/protein acetyltransferases (HATs) promote
      chromatin accessibility, gene transcription and the function of multiple
      transcription factors and nonhistone proteins. We now report that conditional
      deletion or pharmacologic inhibition of one HAT, p300 (also known as Ep300 or
      KAT3B), in Foxp3(+) T(reg) cells increased T cell receptor-induced apoptosis in
      T(reg) cells, impaired T(reg) cell suppressive function and peripheral T(reg)
      cell induction, and limited tumor growth in immunocompetent but not in
      immunodeficient mice. Our data thereby demonstrate that p300 is important for
      Foxp3(+) T(reg) cell function and homeostasis in vivo and in vitro, and identify
      mechanisms by which appropriate small-molecule inhibitors can diminish T(reg)
      cell function without overtly impairing T effector cell responses or inducing
      autoimmunity. Collectively, these data suggest a new approach for cancer
      immunotherapy.

PMID- 23955713
TI  - Vessel architectural imaging identifies cancer patient responders to anti
      angiogenic therapy.
AB  - Measurement of vessel caliber by magnetic resonance imaging (MRI) is a valuable
      technique for in vivo monitoring of hemodynamic status and vascular development,
      especially in the brain. Here, we introduce a new paradigm in MRI termed vessel
      architectural imaging (VAI) that exploits an overlooked temporal shift in the
      magnetic resonance signal, forming the basis for vessel caliber estimation, and
      show how this phenomenon can reveal new information on vessel type and function
      not assessed by any other noninvasive imaging technique. We also show how this
      biomarker can provide new biological insights into the treatment of patients with
      cancer. As an example, we demonstrate using VAI that anti-angiogenic therapy can
      improve microcirculation and oxygen saturation and reduce vessel calibers in
      patients with recurrent glioblastomas and, more crucially, that patients with
      these responses have prolonged survival. Thus, VAI has the potential to identify
      patients who would benefit from therapies. 

PMID- 23955712
TI  - Activation of the Nlrp3 inflammasome in infiltrating macrophages by
      endocannabinoids mediates beta cell loss in type 2 diabetes.
AB  - Type 2 diabetes mellitus (T2DM) progresses from compensated insulin resistance to
      beta cell failure resulting in uncompensated hyperglycemia, a process replicated
      in the Zucker diabetic fatty (ZDF) rat. The Nlrp3 inflammasome has been
      implicated in obesity-induced insulin resistance and beta cell failure.
      Endocannabinoids contribute to insulin resistance through activation of
      peripheral CB1 receptors (CB1Rs) and also promote beta cell failure. Here we show
      that beta cell failure in adult ZDF rats is not associated with CB1R signaling in
      beta cells, but rather in M1 macrophages infiltrating into pancreatic islets, and
      that this leads to activation of the Nlrp3-ASC inflammasome in the macrophages.
      These effects are replicated in vitro by incubating wild-type human or rodent
      macrophages, but not macrophages from CB1R-deficient (Cnr1(-/-)) or Nlrp3(-/-)
      mice, with the endocannabinoid anandamide. Peripheral CB1R blockade, in vivo
      depletion of macrophages or macrophage-specific knockdown of CB1R reverses or
      prevents these changes and restores normoglycemia and glucose-induced insulin
      secretion. These findings implicate endocannabinoids and inflammasome activation
      in beta cell failure and identify macrophage-expressed CB1R as a therapeutic
      target in T2DM.

PMID- 23955714
TI  - PDK1 decreases TACE-mediated alpha-secretase activity and promotes disease
      progression in prion and Alzheimer's diseases.
AB  - alpha-secretase-mediated cleavage of amyloid precursor protein (APP) precludes
      formation of neurotoxic amyloid-beta (Abeta) peptides, and alpha-cleavage of
      cellular prion protein (PrP(C)) prevents its conversion into misfolded,
      pathogenic prions (PrP(Sc)). The mechanisms leading to decreased alpha-secretase
      activity in Alzheimer's and prion disease remain unclear. Here, we find that
      tumor necrosis factor-alpha-converting enzyme (TACE)-mediated alpha-secretase
      activity is impaired at the surface of neurons infected with PrP(Sc) or isolated
      from APP-transgenic mice with amyloid pathology. 3-phosphoinositide-dependent
      kinase-1 (PDK1) activity is increased in neurons infected with prions or affected
      by Abeta deposition and in the brains of individuals with Alzheimer's disease.
      PDK1 induces phosphorylation and caveolin-1-mediated internalization of TACE.
      This dysregulation of TACE increases PrP(Sc) and Abeta accumulation and reduces
      shedding of TNF-alpha receptor type 1 (TNFR1). Inhibition of PDK1 promotes
      localization of TACE to the plasma membrane, restores TACE-dependent alpha
      secretase activity and cleavage of APP, PrP(C) and TNFR1, and attenuates PrP(Sc)-
      and Abeta-induced neurotoxicity. In mice, inhibition or siRNA-mediated silencing
      of PDK1 extends survival and reduces motor impairment following PrP(Sc) infection
      and in APP-transgenic mice reduces Alzheimer's disease-like pathology and memory
      impairment. 

PMID- 23955715
TI  - Synergistic effects of hypertension and aging on cognitive function and
      hippocampal expression of genes involved in beta-amyloid generation and
      Alzheimer's disease.
AB  - Strong epidemiological and experimental evidence indicate that hypertension in
      the elderly predisposes to the development of Alzheimer's disease (AD), but the
      underlying mechanisms remain elusive. The present study was designed to
      characterize the additive/synergistic effects of hypertension and aging on the
      expression of genes involved in beta-amyloid generation and AD in the
      hippocampus, an area of brain contributing to higher cognitive function, which is
      significantly affected by AD both in humans and in mouse models of the disease.
      To achieve that goal, we induced hypertension in young (3 mo) and aged (24 mo)
      C57BL/6 mice by chronic (4 wk) infusion of angiotensin II and assessed changes in
      hippocampal mRNA expression of genes involved in amyloid precursor protein (APP)
      dependent signaling, APP cleavage, Abeta processing and Abeta-degradation,
      synaptic function, dysregulation of microtubule-associated tau protein, and
      apolipoprotein-E signaling. Aged hypertensive mice exhibited spatial memory
      impairments in the Y-maze and impaired performance in the novel object
      recognition assay. Surprisingly, hypertension in aging did not increase the
      expression of APP, beta- and gamma-secretases, or genes involved in tauopathy.
      These genes are all involved in the early onset form of AD. Yet, hypertension in
      aging was associated with changes in hippocampal expression of APP binding
      proteins, e.g., [Mint3/amyloid beta A4 precursor protein-binding family A member
      3 (APBA3), Fe65/amyloid beta A4 precursor protein-binding family B member 1
      (APBB1)], amyloid beta (A4) precursor-like protein 1 (APLP1), muscarinic M1
      receptor, and serum amyloid P component, all of which may have a role in the
      pathogenesis of late-onset AD. The hippocampal gene expression signature observed
      in aged hypertensive mice in the present study provides important clues for
      subsequent studies to elucidate the mechanisms by which hypertension may
      contribute to the pathogenesis and clinical manifestation of AD. 

PMID- 23955716
TI  - Endothelial cell transfusion ameliorates endothelial dysfunction in 5/6
      nephrectomized rats.
AB  - Endothelial dysfunction is prevalent in chronic kidney disease. This study tested
      the hypothesis that transfusion of rat aortic endothelial cells (ECs) ameliorates
      endothelial dysfunction in a rat model of chronic kidney disease. Male Sprague
      Dawley rats underwent sham surgery or 5/6 nephrectomy (Nx). Five weeks after Nx,
      EC (1.5 * 10(6) cells/rat) or vehicle were transfused intravenously. One week
      later, vascular reactivity of mesenteric artery was assessed on a wire myograph.
      Sensitivity of endothelium-dependent relaxation to acetylcholine and maximum
      vasodilation were impaired by Nx and improved by EC transfusion. Using selective
      pharmacological nitric oxide synthase isoform inhibitors, we demonstrated that
      the negative effect of Nx on endothelial function and rescue by EC transfusion
      are, at least in part, endothelial nitric oxide synthase mediated. Plasma
      asymmetric dimethylarginine was increased by Nx and decreased by EC transfusion,
      whereas mRNA expression of dimethylarginine dimethylaminohydrolases 1 (DDAH1) was
      decreased by Nx and restored by EC transfusion. Immunohistochemical staining
      confirmed that local expression of DDAH1 is decreased by Nx and increased by EC
      transfusion. In conclusion, EC transfusion attenuates Nx-induced endothelium
      dependent vascular dysfunction by regulating DDAH1 expression and enhancing
      endothelial nitric oxide synthase activity. These results suggest that EC-based
      therapy could provide a novel therapeutic strategy to improve vascular function
      in chronic kidney disease. 

PMID- 23955717
TI  - Nox2 as a potential target of mitochondrial superoxide and its role in
      endothelial oxidative stress.
AB  - Superoxide (O2(.-)) production by the NADPH oxidases is implicated in the
      pathogenesis of many cardiovascular diseases, including hypertension. We have
      previously shown that activation of NADPH oxidases increases mitochondrial O2(.-)
      which is inhibited by the ATP-sensitive K(+) channel (mitoKATP) inhibitor 5
      hydroxydecanoic acid and that scavenging of mitochondrial or cytoplasmic O2(.-)
      inhibits hypertension. We hypothesized that mitoKATP-mediated mitochondrial O2(.
      ) potentiates cytoplasmic O2(.-) by stimulation of NADPH oxidases. In this work
      we studied Nox isoforms as a potential target of mitochondrial O2(.-). We tested
      contribution of reverse electron transfer (RET) from complex II to complex I in
      mitochondrial O2(.-) production and NADPH oxidase activation in human aortic
      endothelial cells. Activation of mitoKATP with low dose of diazoxide (100 nM)
      decreased mitochondrial membrane potential (tetramethylrhodamine methyl ester
      probe) and increased production of mitochondrial and cytoplasmic O2(.-) measured
      by site-specific probes and mitoSOX. Inhibition of RET with complex II inhibitor
      (malonate) or complex I inhibitor (rotenone) attenuated the production of
      mitochondrial and cytoplasmic O2(.-). Supplementation with a mitochondria
      targeted SOD mimetic (mitoTEMPO) or a mitochondria-targeted glutathione
      peroxidase mimetic (mitoEbselen) inhibited production of mitochondrial and
      cytoplasmic O2(.-). Inhibition of Nox2 (gp91ds) or Nox2 depletion with small
      interfering RNA but not Nox1, Nox4, or Nox5 abolished diazoxide-induced O2(.-)
      production in the cytoplasm. Treatment of angiotensin II-infused mice with RET
      inhibitor dihydroethidium (malate) significantly reduced blood pressure. Our
      study suggests that mitoKATP-mediated mitochondrial O2(.-) stimulates cytoplasmic
      Nox2, contributing to the development of endothelial oxidative stress and
      hypertension. 

PMID- 23955719
TI  - Drug-eluting balloon for instent restenosis.

PMID- 23955718
TI  - Quantitative optical imaging of vascular response in vivo in a model of
      peripheral arterial disease.
AB  - The mouse hind limb ischemia (HLI) model is well established for studying
      collateral vessel formation and testing therapies for peripheral arterial
      disease, but there is a lack of quantitative techniques for intravitally
      analyzing blood vessel structure and function. To address this need, non
      invasive, quantitative optical imaging techniques were developed to assess the
      time-course of recovery in the mouse HLI model. Hyperspectral imaging and optical
      coherence tomography (OCT) were used to non-invasively image hemoglobin oxygen
      saturation and microvessel morphology plus blood flow, respectively, in the
      anesthetized mouse after induction of HLI. Hyperspectral imaging detected
      significant increases in hemoglobin saturation in the ischemic paw as early as 3
      days after femoral artery ligation (P < 0.01), and significant increases in
      distal blood flow were first detected with OCT 14 days postsurgery (P < 0.01).
      Intravital OCT images of the adductor muscle vasculature revealed corkscrew
      collateral vessels characteristic of the arteriogenic response to HLI. The
      hyperspectral imaging and OCT data significantly correlated with each other and
      with laser Doppler perfusion imaging (LDPI) and tissue oxygenation sensor data (P
      < 0.01). However, OCT measurements acquired depth-resolved information and
      revealed more sustained flow deficits following surgery that may be masked by
      more superficial measurements (LDPI, hyperspectral imaging). Therefore,
      intravital OCT may provide a robust biomarker for the late stages of ischemic
      limb recovery. This work validates non-invasive acquisition of both functional
      and morphological data with hyperspectral imaging and OCT. Together, these
      techniques provide cardiovascular researchers an unprecedented and comprehensive
      view of the temporal dynamics of HLI recovery in living mice. 

PMID- 23955720
TI  - Early detection of high voltage lead failure with an unusual and unexpected
      device alert.

PMID- 23955721
TI  - Preparation and characterization of PEG-PPG-PEG copolymer/pregelatinized starch
      blends for use as resorbable bone hemostatic wax.
AB  - In this study, polymer blends between PEG-PPG-PEG copolymer mixtures and
      pregelatinized starch at various compositions ranging from 0 to 3 % by weight
      were prepared and evaluated for potential use as novel resorbable bone hemostatic
      wax. It was found that the prepared samples had sufficient smearability for use
      as a bone wax. An addition of pregelatinized starch increased the hardness,
      smoothness and consistency of the texture while decreasing the adherence to
      glove. Thermal analysis indicated that the heat of fusion slightly decreased with
      increasing pregelatinized starch content. Compressive stiffness tended to
      decrease with increasing starch content for concentrations lower than 20 %, but
      re-increased at higher starch levels. In contrast, adherence deformation
      increased initially, but then decreased with increasing starch content. This
      behavior was related to the dependence of softening or reinforcing effect on the
      level of starch concentration in the samples. Adherence load and energy decreased
      with the addition of pregelatinized starch implying the decrease in adhesiveness
      of the samples. Furthermore, increasing the pregelatized starch amount also
      increased the liquid sealing duration of the samples at both 23 and 37  degrees
      C. Cytotoxicity tests against osteoblasts using a MTT assay revealed that the all
      the prepared samples and their raw materials did not show any cytotoxic
      potential. Formulations containing pregelatinized starch content between 20 and
      30 % were found to show optimized performance.

PMID- 23955722
TI  - Cadmium exposure and clinical cardiovascular disease: a systematic review.
AB  - Mounting evidence supports that cadmium, a toxic metal found in tobacco, air and
      food, is a cardiovascular risk factor. Our objective was to conduct a systematic
      review of epidemiologic studies evaluating the association between cadmium
      exposure and cardiovascular disease. Twelve studies were identified. Overall, the
      pooled relative risks (95% confidence interval) for cardiovascular disease,
      coronary heart disease, stroke, and peripheral arterial disease were: 1.36 (95%
      CI: 1.11, 1.66), 1.30 (95% CI: 1.12, 1.52), 1.18 (95% CI: 0.86, 1.59), and 1.49
      (95% CI: 1.15, 1.92), respectively. The pooled relative risks for cardiovascular
      disease in men, women and never smokers were 1.29 (1.12, 1.48), 1.20 (0.92, 1.56)
      and 1.27 (0.97, 1.67), respectively. Together with experimental evidence, our
      review supports the association between cadmium exposure and cardiovascular
      disease, especially for coronary heart disease. The number of studies with
      stroke, heart failure (HF) and peripheral arterial disease (PAD) endpoints was
      small. More studies, especially studies evaluating incident endpoints, are
      needed.

PMID- 23955723
TI  - Anatomical and functional impairment of the nerve fiber layer in patients with
      optic nerve head drusen.
AB  - OBJECTIVE: To evaluate anatomical and functional impairment of the retinal nerve
      fiber layer (RNFL) using optical coherence tomography (OCT) and automated
      perimetry in patients with optic nerve head drusen (ONHD). MATERIALS AND METHODS:
      Sixty-six eyes (66 patients) were studied with ONHD - confirmed by ultrasound B
      scan - and 70 eyes (70 subjects) of healthy control subjects. ONHD cases were
      categorised as visible or hidden. Average RNFL thickness and measurements in
      terms of the quadrants were analysed using both time-domain optical coherence
      tomography (TD-OCT) and spectral-domain optical coherence tomography (SD-OCT).
      Anatomical and visual field alteration of RNFL between visible and hidden ONHD
      and control groups were compared. RESULTS: Average RNFL thickness in ONHD
      patients was 94 MUm (TD-OCT) and 88 MUm (SD-OCT), and in controls 107 MUm (TD
      OCT) and 96 MUm (SD-OCT), with statistically significant differences between both
      OCTs. All quadrants analysed showed significant differences except the temporal
      quadrant. The differences were not significant between hidden drusen and
      controls.Visual field examination in ONHD showed alterations in 56 %. Alterations
      were greater in visible drusen in relation to non-visible drusen, but there were
      no significant differences.The association between RNFL defects in superior,
      inferior and temporal quadrants and visual field defects showed a statistical
      relation with visible ONHD, but not in hidden ONHD. CONCLUSIONS: ONHD caused
      anatomical and functional damage of the RNFL, with a clear association between
      the alteration in ONHD and visual field defects in visible drusen cases.

PMID- 23955724
TI  - Relationship between mean platelet volume and retinopathy in patients with type 2
      diabetes mellitus.
AB  - OBJECTIVES: To evaluate the effect of mean platelet volume (MPV) on diabetic
      retinopathy in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: In
      this study, ocular findings and MPV values were retrospectively reviewed in 192
      patients with type 2 diabetes mellitus. The patients were classified into four
      groups according to ocular findings, as follows: group 1, diabetic patients
      without diabetic retinopathy (n = 70); group 2, diabetic patients with non
      proliferative diabetic retinopathy (n = 64); group 3, diabetic patients with
      proliferative diabetic retinopathy (n = 58); and group 4, healthy controls (n =
      100). RESULTS: A significant difference was found in MPV values between groups 2
      and 4 (P = 0.001), between groups 3 and 4 (P = 0.001), and between groups 1 and 4
      (P = 0.004). No significant difference was found in MPV values between groups 1
      and 2 (P = 0.241) and between groups 2 and 3 (P = 0.460); whereas there was a
      statistically significant difference between groups 1 and 3 (P = 0.015). The
      three diabetic groups (groups 1, 2, and 3) were compared with each other. While
      there was a statistically significant difference between groups 1 and 3 (P =
      0.015), there was no significance between groups 2 and 3 (P = 0.46), and between
      group 1 and 2 (P = 0.241). Logistic regression analysis found a 1.40-fold
      increase in the risk of retinopathy development (OR: 1.404; P = 0.002) and a 1.46
      fold increase in the risk of proliferative diabetic retinopathy (OR: 1.466; P =
      0.002) as the MPV value increased. CONCLUSIONS: In diabetic patients, the risk of
      retinopathy development increases with higher MPV values.

PMID- 23955725
TI  - Thermodynamic properties of the alpha-quartz-type and rutile-type GeO2 from first
      principles calculations.
AB  - Phonon density-of-states and related thermodynamic properties of the alpha-quartz
      type and rutile-type germanium dioxide (GeO2) are investigated from density
      functional perturbation theory. The significant density-of-states at the low
      frequencies in the alpha-quartz-type GeO2 are at the origin of (i) its lower
      internal energy below 250 K, (ii) its smaller free energy, (iii) its higher
      entropy, (iv) its lower Debye temperature and (v) its larger positive linear
      thermal expansion, with respect to the rutile-type GeO2.

PMID- 23955726
TI  - Retrospective study of endoscopic submucosal tunnel dissection (ESTD) for
      surgical resection of esophageal leiomyoma.
AB  - BACKGROUND: Esophageal leiomyoma is benign and often asymptomatic, but if the
      tumor is too large or obstructive, it should be resected. The aim of this study
      was to compare a novel approach, endoscopic submucosal tunnel dissection (ESTD),
      with a more established method, endoscopic submucosal dissection (ESD). METHODS:
      This was a retrospective study of 39 patients in Chongqing Xinqiao Hospital,
      China, undergoing resection for leiomyoma >2 cm in diameter, or 1.5-2.0 cm in
      diameter with symptoms of obstructive dysphagia. Epidemiological data, presenting
      symptoms, diagnostic investigations, tumor location, histopathological findings,
      and safety and efficacy of surgical resection were analyzed. RESULTS: Mean tumor
      sizes in the ESTD (n = 18; mean age = 36.7 +/- 6.3 years) and ESD (n = 21; age =
      41.0 +/- 4.4 years) groups were 3.3 +/- 0.7 and 3.0 +/- 0.4 cm, respectively. The
      male:female ratio was 25:14, with a distribution of lesions among the lower,
      middle, and upper esophagus of 22:14:3. Operating time was significantly shorter
      (p < 0.05) for ESTD (67.5 +/- 9.5 min) than for ESD (87.2 +/- 7.7 min), while
      incision healing was faster (p < 0.05) for ESTD (14.7 +/- 2.5 days) than for ESD
      (57.9 +/- 7.5 days). Hospital stay was also shorter (p < 0.05) for ESTD (2.3 +/-
      0.5 days) than for ESD (5.7 +/- 1.0 days). Bleeding was the only complication
      with ESTD (3/18 patients), with no significant difference in the incidence of
      complications between groups. ESTD was rapidly learned by surgeons. CONCLUSION:
      ESTD is a safe and effective treatment for esophageal leiomyoma, with advantages
      over ESD.

PMID- 23955727
TI  - Impact of a bladder scan protocol on discharge efficiency within a care pathway
      for ambulatory inguinal herniorraphy.
AB  - BACKGROUND: Postoperative urinary retention (POUR) is a common complication of
      ambulatory inguinal herniorraphy, with an incidence reaching 38%, and many
      surgeons require patients to void before discharge. This study aimed to assess
      whether the implementation of a bladder scan-based voiding protocol reduces the
      time until discharge after ambulatory inguinal herniorraphy without increasing
      the rate of POUR. METHODS: As part of a perioperative care pathway, a protocol
      was implemented to standardize decision making after elective inguinal hernia
      repair (February 2012). Patients were assessed with a bladder scan, and those
      with <600 mL of urine were discharged home, whereas those with more than 600 mL
      of urine had an in-and-out catheterization before discharge. The patients
      received written information about urinary symptoms and instructions to present
      to the emergency department if they were unable to void at home. An audit of
      scheduled outpatient inguinal hernia repairs between October 2011 and July 2012
      was performed. Comparisons were made using the t test, Fisher's exact test, and
      Wilcoxon rank sum test where appropriate. Statistical significance was defined a
      priori as a p value lower than 0.05. RESULTS: During the study period, 124
      patients underwent hernia repair: 60 before and 64 after implementation of the
      protocol. The findings showed no significant differences in patient
      characteristics, laparoscopic approach (35 vs. 33%; p = 0.80), proportion
      receiving general anesthesia (70 vs. 73%; p = 0.67), or amount of intravenous
      fluids given (793 vs. 663 mL; p = 0.07). The proportion of patients voiding
      before discharge was higher after protocol implementation (73 vs. 89%; p = 0.02).
      The protocol had no impact on median time to discharge (190 vs. 205 min; p =
      0.60). Only one patient in each group presented to the emergency department with
      POUR (2%). CONCLUSION: After ambulatory inguinal herniorraphy, implementation of
      a bladder scan-based voiding protocol did not result in earlier discharge. The
      incidence of POUR was lower than reported in the literature.

PMID- 23955728
TI  - Does nasogastric tube decompression get used less often with laparoscopic and
      hand-assisted compared with open colectomy?
AB  - INTRODUCTION: Laparoscopic surgery is associated with well-known benefits, one of
      which is earlier return of bowel function. Since the laparoscopic approach to
      colon resections was introduced in the early 1990s, it has become the standard of
      care. Hand-assisted laparoscopic surgery (HALS) is a surgical approach in which
      dissection is facilitated by the surgeon's hand within the abdominal cavity
      during laparoscopy. The purpose of this study was to compare the incidence of
      postoperative ileus and the need for nasogastric tube (NGT) decompression in
      patients undergoing elective colon resections. METHODS AND PROCEDURES: Following
      institutional review board approval, we performed a retrospective review of a
      prospectively collected database. Included were patients who underwent elective
      left-sided large bowel resections between 2009 and 2012. Exclusion criteria were
      urgent operation, stoma creation, ASA IV classification, NGT left in place at the
      end of surgery, and postoperative anastomotic leakage. Patients were divided into
      three groups: laparoscopic surgery, HALS, and open surgery. We evaluated the
      incidence of postoperative ileus and the use of nasogastric decompression in each
      group. RESULTS: A total of 243 patients were included in this study; 73 patients
      underwent open surgery, 89 patients underwent HALS, and 81 patients underwent
      laparoscopic surgery. The proportion of patients who needed postoperative
      nasogastric decompression was significantly reduced in patients undergoing
      laparoscopic surgery (3.7%) or HALS (4.5%) compared with those who underwent open
      resection (17.8%). The time from surgery to first flatus and first bowel
      movement, the time to tolerate solid diet, and the total length of postoperative
      hospital stay also were all significantly reduced in the laparoscopic and HALS
      groups compared with the open surgery group. There were no significant
      differences in any of these measures between the laparoscopic group and the hand
      assisted group. CONCLUSIONS: Like laparoscopy, HALS is associated with less
      postoperative ileus and necessitates less NGT decompression than does open
      surgery.

PMID- 23955729
TI  - Proteomics analysis of contact-initiated eph receptor-ephrin signaling.
AB  - Large-scale biochemical analysis of cell-specific signaling can be interrogated
      in cocultures of Eph receptor- and ephrin-expressing cells by combining
      proteomics analysis with cell-specific metabolic labeling. In this chapter, we
      describe how to perform such large-scale analysis, including the generation of
      cells stably expressing the receptors and ligands of interest, optimization steps
      for Eph-ephrin coculture, and the proteomics analysis. As the experimental
      details may vary depending on the specific system that is being interrogated, the
      goal of the chapter is mainly to provide sufficient experimental context for
      experienced researchers to set up and conduct these experiments. 

PMID- 23955730
TI  - Control of vascular tube morphogenesis and maturation in 3D extracellular
      matrices by endothelial cells and pericytes.
AB  - An important advance using in vitro EC tube morphogenesis and maturation models
      has been the development of systems using serum-free defined media. Using this
      approach, the growth factors and cytokines which are actually necessary for these
      events can be determined. The first model developed by our laboratory was such a
      system where we showed that phorbol ester was needed in order to promote survival
      and tube morphogenesis in 3D collagen matrices. Recently, we have developed a new
      system in which the hematopoietic stem cell cytokines, stem cell factor (SCF),
      interleukin-3 (IL-3), and stromal derived factor-1alpha (SDF-1alpha) were added
      in conjunction with FGF-2 to promote human EC tube morphogenesis in 3D collagen
      matrices under serum-free defined conditions. This new model using SCF, IL-3, SDF
      1alpha, and FGF-2 also works well following the addition of pericytes where EC
      tube formation occurs, pericytes are recruited to the tubes, and vascular
      basement membrane matrix assembly occurs following EC-pericyte interactions. In
      this chapter, we describe several in vitro assay models that we routinely utilize
      to investigate the molecular requirements that are critical to EC tube formation
      and maturation events in 3D extracellular matrix environments. 

PMID- 23955731
TI  - Analyzing cell-cell interactions in 3-dimensional adhesion assays.
AB  - The organization of cells is key to the proper formation and function of tissues
      and it appears to be dependent upon various intracellular and extracellular
      signals. These signals come from cell-cell interactions, as well as interactions
      with the surrounding extracellular milieu. In order to investigate these
      properties and interactions among cells, our lab utilizes and has developed
      several techniques that provide a 3-dimensional, in vivo-like environment for in
      vitro cell culture. In this chapter, we describe several techniques for isolating
      primary cardiac cells, including myocytes, endothelial cells, and fibroblasts. In
      addition, we discuss and outline an adhesion assay and an aggregation assay that
      can be used for numerous cell types, as well as a collagen gel assay for
      examination of cell-cell and cell-matrix interactions. 

PMID- 23955732
TI  - Production of spontaneously beating neonatal rat heart tissue for calcium and
      contractile studies.
AB  - Neonatal rat ventricular myocytes (NRVM) and fibroblasts (FB) serve as in vitro
      models for studying fundamental mechanisms underlying cardiac pathologies, as
      well as identifying potential therapeutic targets. Typically, these cell types
      are separated using Percoll density gradient procedures. Cells located between
      the Percoll bands (interband cells [IBCs]), which contain less mature NRVM and a
      variety of non-myocytes, including coronary vascular smooth muscle cells and
      endothelial cells (ECs), are routinely discarded. However, we have demonstrated
      that IBCs readily attach to extracellular matrix-coated coverslips, plastic
      culture dishes, and deformable membranes to form a 2-dimensional cardiac tissue
      layer which quickly develops spontaneous contraction within 24 h, providing a
      robust coculture model for the study of cell-to-cell signaling and contractile
      studies. Below, we describe methods that provide good cell yield and viability of
      IBCs during isolation of NRVM and FB obtained from 0- to 3-day-old neonatal rat
      pups. Basic characterization of IBCs and methods for use in intracellular calcium
      and contractile experiments are also presented. This method maximizes the use of
      cells obtained from neonatal rat hearts. 

PMID- 23955733
TI  - Paracrine communication between mechanically stretched myocytes and fibroblasts.
AB  - Mechanical stretch is a major factor for myocardial hypertrophy and heart
      failure. Stretch activates mechanical sensors from cardiac myocytes, leading to a
      series of signal transduction cascades, which can result in cell malfunction and
      remodeling. It is well known that mechanical stretch also induces the release of
      paracrine factors from cardiac fibroblasts, as well as myocytes. Due to
      complicated circumstance of heart tissue, it is difficult to fully investigate
      the characteristics of these factors in situ. Here we describe static stretch and
      conditioned medium experiments as methods to examine the function of paracrine
      factors between primary cultured cardiac myocytes and fibroblasts. 

PMID- 23955734
TI  - Assessing blood-brain barrier function using in vitro assays.
AB  - The impermeability of the blood-brain barrier (BBB) is due to a number of
      properties including tight junctions on adjoining endothelial cells, absence of
      pinocytic vesicles, and expression of multidrug transporters. Although the
      permeability of many chemicals can be predicted by their polarity, or oil/water
      partition coefficient, many lipophilic chemicals are not permeable because of
      multidrug transporters at the luminal and abluminal membranes. In contrast, many
      nutrients, which are usually polar, cross the BBB more readily than predicted by
      their oil/water partition coefficients due to the expression of specific nutrient
      transporters. In vitro models are being developed because rodent models are of
      low input and relatively expensive. Isolated brain microvessels and cell culture
      models each offers certain advantages and disadvantages. Isolated brain
      microvessels are useful in measuring multidrug drug transporters and tight
      junction integrity, whereas cell culture models allow the investigator to measure
      directional transport and can be genetically manipulated. In this chapter, we
      describe how to isolate large batches of brain microvessels from freshly
      slaughtered cows. The different steps in the isolation procedure include density
      gradient centrifugations and filtering. Purity is determined microscopically and
      by marker enzymes. Permeability is assessed by measuring the uptake of
      fluorescein-labeled dextran in an assay that has been optimized to have a large
      dynamic range and low inter-day variability. We also describe how to evaluate
      transendothelial cell electrical resistance and paracellular transport in cell
      culture models. 

PMID- 23955735
TI  - Methods to assess tissue permeability.
AB  - An essential requirement for adequate organ performance is the formation of
      permeability barriers that separate and maintain compartments of distinctive
      structure and function. The endothelial cell lining of the vasculature defines a
      semipermeable barrier between the blood and interstitial spaces of all organs.
      Disruption of the endothelial cell barrier can result in increased permeability
      and vascular leak. These effects are associated with multiple systemic disease
      processes and can accompany acute tissue responses to injury. The mechanisms that
      control barrier function are complex and their full understanding requires a
      multidisciplinary approach. The use of in vivo permeability data often
      complements molecular findings and adds power to the studies. The interaction of
      multiple cell types and tissues present only in mammalian models allows for
      testing of hypothesis and establishing the physiological significance of the
      results. In this chapter we describe simple methods that can be used
      systematically to measure the permeability profile of several organs. 

PMID- 23955736
TI  - In vivo quantification of metastatic tumor cell adhesion in the pulmonary
      microvasculature.
AB  - In vivo and ex vivo fluorescence video microscopy used to be a well-established
      method in life science with a variety of applications, such as in inflammation or
      cancer research. In this book chapter, we describe a model of in vivo
      fluorescence microscopy of the rat's lung with the exclusive advantage of
      qualitative and quantitative in vivo analysis of cell adhesion within the complex
      microenvironment of the ventilated and perfused lung. Observation can include
      real-time, time-lapse, or fast-motion analysis. In our laboratory, we have used
      the model for qualitative and quantitative real-time analyses of metastatic colon
      cancer cell adhesion within the rat's pulmonary microcirculation. Using some
      modifications in another series, we have also applied the model to analyze
      thrombocyte and leucocyte adhesion within the pulmonary capillaries in
      experimental sepsis. For interventional studies, injected cells or animals may be
      pretreated with various reagents or drugs for further analysis of adhesion
      molecules involved in tumor cell-endothelial cell interactions. 

PMID- 23955737
TI  - Cell membrane vesicles as a tool for the study of direct epithelial-stromal
      interaction: lessons from CD147.
AB  - Communication between the epithelial and stromal tissue layers, separated by
      basement membrane, is known to provide the information necessary for development,
      differentiation, and homeostasis. These interactions are altered in benign or
      malignant diseases, in particular when the basement membrane barrier is disrupted
      allowing a greater proximity between the two cell layers that triggers tissue
      remodeling. Epithelial-stromal interactions (ESI) have been examined in vitro by
      various approaches that can be broadly divided into interactions arising from
      secreted diffusible factors and interactions through direct cell-cell contact.
      Here we describe a method for the study of direct ESI through CD147, an adhesion
      molecule present on the epithelial cell surface and which is known to interact
      with stromal cells, such as fibroblasts and endothelial cells, and signal them to
      increase production of matrix metalloproteinases. This method can be extended to
      other adhesion molecules involved in ESI. 

PMID- 23955738
TI  - Microencapsulation of stem cells to study cellular interactions.
AB  - Microencapsulation is a technique used in both controlled delivery of materials
      over time as well as preservation of these materials while delivery is occurring.
      The range of materials able to be encapsulated is variable, from drugs to living
      cells. The latter is described here. Electrospray microencapsulation applies a
      high-voltage field, through which a polymeric material is extruded. A gelling
      bath, comprising a cross-linking material, is used to create a stable hydrogel
      containing secondary substances intended for delivery. Control of extrusion
      parameters, such as flow rate and voltage, allows for specification of diameter
      and pore sizes of the microcapsules. 

PMID- 23955739
TI  - Cell-surface protein-protein interaction analysis with time-resolved FRET and
      snap-tag technologies.
AB  - Forster resonance energy transfer (FRET) is a proximity-dependent quantum effect
      that allows the measurement of protein interactions and conformational changes
      which are invisible to traditional forms of fluorescence or electron microscopy.
      However, FRET experiments often have difficulty detecting interactions that are
      transient and localized or occur in low abundance against a large background.
      This protocol describes a method of improving on the sensitivity and
      quantifiability of FRET experiments by using time-specific detection to isolate
      FRET-mediated acceptor emission from cross-talk excitation and all other sources
      of nonspecific fluorescence background. 

PMID- 23955740
TI  - Single cell analysis of lipid rafts.
AB  - Lipid rafts are plasma membrane microdomains that serve as platforms for the
      assembly of proteins involved in signal transduction pathways. Given that lipid
      rafts are relatively resistant to cold extraction with nonionic detergents, lipid
      raft associated and nonassociated proteins have been identified using biochemical
      methods such as sucrose-gradient density centrifugation. For identification of
      raft-associated proteins in individual cells, imaging methods, such as
      fluorescence microscopy, can be used. Detergent solubilization of non-raft
      regions of the plasma membrane and extraction of non-raft associated proteins are
      done on cells affixed to microscope slides and prior to immunostaining. This
      methodology has the advantages of requiring smaller cell numbers than traditional
      biochemical methods and also permits the study of migration of signaling proteins
      into and out of rafts during cell activation. An additional adaptation of the
      method allows identification of lipid raft-associated proteins during cognate
      interactions between cells. Here, as an example, we describe the methodology used
      in our laboratory to study lipid raft-associated molecules during T lymphocyte
      interactions with antigen-presenting cells. 

PMID- 23955741
TI  - Micropatterning cell adhesion on polyacrylamide hydrogels.
AB  - Cell shape and substrate rigidity play critical roles in regulating cell
      behaviors and fate. Controlling cell shape on elastic adhesive materials holds
      great promise for creating a physiologically relevant culture environment for
      basic and translational research and clinical applications. However, it has been
      technically challenging to create high-quality adhesive patterns on compliant
      substrates. We have developed an efficient and economical method to create
      precise micron-scaled adhesive patterns on the surface of a hydrogel (Rape et
      al., Biomaterials 32:2043-2051, 2011). This method will facilitate the research
      on traction force generation, cellular mechanotransduction, and tissue
      engineering, where precise controls of both materials rigidity and adhesive
      patterns are important. 

PMID- 23955742
TI  - Measuring cell-cell tugging forces using bowtie-patterned mPADs (microarray post
      detectors).
AB  - Cells generate traction forces upon adhesion to the extracellular matrix as well
      as to neighboring cells. These forces are important for the growth and
      maintenance of adhesion structures such as focal adhesions and adherens
      junctions, and may play roles in tissue development. Here, we describe a method
      for measuring the tugging force transmitted across the cell-cell junction between
      two paired cells. 

PMID- 23955743
TI  - Generation and analysis of biosensors to measure mechanical forces within cells.
AB  - The inability to measure mechanical forces within cells has been limiting our
      understanding of how mechanical information is processed on the molecular level.
      In this chapter, we describe a method that allows the analysis of force
      propagation across distinct proteins within living cells using Forster resonance
      energy transfer (FRET)-based biosensors. 

PMID- 23955744
TI  - Proteomic analysis of the left ventricle post-myocardial infarction to identify
      in vivo candidate matrix metalloproteinase substrates.
AB  - Left ventricular remodeling post-myocardial infarction (MI) involves a multitude
      of mechanisms that regulate the repair response. Matrix metalloproteinases (MMPs)
      are a major family of proteolytic enzymes that coordinate extracellular matrix
      turnover. MMP-7 or MMP-9 deletion attenuate adverse remodeling post-MI, but the
      mechanisms have not been fully clarified. Both MMP-7 and MMP-9 have a large
      number of known in vitro substrates, but in vivo substrates for these two MMPs in
      the myocardial infarction setting are incompletely identified. Advances in
      proteomic techniques have enabled comprehensive profiling of protein expression
      in cells and tissue. In this chapter, we describe a protocol for the proteomic
      analysis of in vivo candidate MMP substrates in the post-MI left ventricle using
      two-dimensional electrophoresis, liquid chromatography coupled with tandem mass
      spectrometry, and immunoblotting. 

PMID- 23955745
TI  - Efficient halftoning based on multiple look-up tables.
AB  - Look-up table (LUT) halftoning is an efficient way to construct halftone images
      and approximately simulate the dot distribution of the learned halftone image
      set. In this paper, a general mechanism named multiple look-up table (MLUT)
      halftoning is proposed to generate the halftones of direct binary search (DBS),
      whereas the high efficient characteristic of the LUT is still preserved. In the
      MLUT, the standard deviation is adopted as an important feature to classify
      various tables. In addition, the proposed quick standard deviation evaluation is
      employed to yield an extremely low computational complexity in calculating the
      standard deviation. In the parameter optimization, the autocorrelation is adopted
      because it can fully characterize the periodicity of dot distribution.
      Experimental results demonstrate that the dot distribution generated by the
      proposed method approximates to that of the DBS, which enables the proposed
      scheme as a very competitive candidate in the copying and printing industry. 

PMID- 23955747
TI  - Pairwise sparsity preserving embedding for unsupervised subspace learning and
      classification.
AB  - Two novel unsupervised dimensionality reduction techniques, termed sparse
      distance preserving embedding (SDPE) and sparse proximity preserving embedding
      (SPPE), are proposed for feature extraction and classification. SDPE and SPPE
      perform in the clean data space recovered by sparse representation and enhanced
      Euclidean distances over noise removed data are employed to measure pairwise
      similarities of points. In extracting informative features, SDPE and SPPE aim at
      preserving pairwise similarities between data points in addition to preserving
      the sparse characteristics. This paper calculates the sparsest representation of
      all vectors jointly by a convex optimization. The sparsest codes enable certain
      local information of data to be preserved, and can endow SDPE and SPPE a natural
      discriminating power, adaptive neighborhood and robust characteristic against
      noise and errors in delivering low-dimensional embeddings. We also mathematically
      show SDPE and SPPE can be effectively extended for discriminant learning in a
      supervised manner. The validity of SDPE and SPPE is examined by extensive
      simulations. Comparison with other related state-of-the-art unsupervised
      algorithms show that promising results are delivered by our techniques. 

PMID- 23955746
TI  - Vector-valued image processing by parallel level sets.
AB  - Vector-valued images such as RGB color images or multimodal medical images show a
      strong interchannel correlation, which is not exploited by most image processing
      tools. We propose a new notion of treating vector-valued images which is based on
      the angle between the spatial gradients of their channels. Through minimizing a
      cost functional that penalizes large angles, images with parallel level sets can
      be obtained. After formally introducing this idea and the corresponding cost
      functionals, we discuss their Gateaux derivatives that lead to a diffusion-like
      gradient descent scheme. We illustrate the properties of this cost functional by
      several examples in denoising and demosaicking of RGB color images. They show
      that parallel level sets are a suitable concept for color image enhancement.
      Demosaicking with parallel level sets gives visually perfect results for low
      noise levels. Furthermore, the proposed functional yields sharper images than the
      other approaches in comparison. 

PMID- 23955748
TI  - A model based iterative reconstruction algorithm for high angle annular dark
      field-scanning transmission electron microscope (HAADF-STEM) tomography.
AB  - High angle annular dark field (HAADF)-scanning transmission electron microscope
      (STEM) data is increasingly being used in the physical sciences to research
      materials in 3D because it reduces the effects of Bragg diffraction seen in
      bright field TEM data. Typically, tomographic reconstructions are performed by
      directly applying either filtered back projection (FBP) or the simultaneous
      iterative reconstruction technique (SIRT) to the data. Since HAADF-STEM
      tomography is a limited angle tomography modality with low signal to noise ratio,
      these methods can result in significant artifacts in the reconstructed volume. In
      this paper, we develop a model based iterative reconstruction algorithm for HAADF
      STEM tomography. We combine a model for image formation in HAADF-STEM tomography
      along with a prior model to formulate the tomographic reconstruction as a maximum
      a posteriori probability (MAP) estimation problem. Our formulation also accounts
      for certain missing measurements by treating them as nuisance parameters in the
      MAP estimation framework. We adapt the iterative coordinate descent algorithm to
      develop an efficient method to minimize the corresponding MAP cost function.
      Reconstructions of simulated as well as experimental data sets show results that
      are superior to FBP and SIRT reconstructions, significantly suppressing artifacts
      and enhancing contrast. 

PMID- 23955749
TI  - Adaptive dictionary learning in sparse gradient domain for image recovery.
AB  - Image recovery from undersampled data has always been challenging due to its
      implicit ill-posed nature but becomes fascinating with the emerging compressed
      sensing (CS) theory. This paper proposes a novel gradient based dictionary
      learning method for image recovery, which effectively integrates the popular
      total variation (TV) and dictionary learning technique into the same framework.
      Specifically, we first train dictionaries from the horizontal and vertical
      gradients of the image and then reconstruct the desired image using the sparse
      representations of both derivatives. The proposed method enables local features
      in the gradient images to be captured effectively, and can be viewed as an
      adaptive extension of the TV regularization. The results of various experiments
      on MR images consistently demonstrate that the proposed algorithm efficiently
      recovers images and presents advantages over the current leading CS
      reconstruction approaches. 

PMID- 23955750
TI  - Real-time object tracking via online discriminative feature selection.
AB  - Most tracking-by-detection algorithms train discriminative classifiers to
      separate target objects from their surrounding background. In this setting, noisy
      samples are likely to be included when they are not properly sampled, thereby
      causing visual drift. The multiple instance learning (MIL) paradigm has been
      recently applied to alleviate this problem. However, important prior information
      of instance labels and the most correct positive instance (i.e., the tracking
      result in the current frame) can be exploited using a novel formulation much
      simpler than an MIL approach. In this paper, we show that integrating such prior
      information into a supervised learning algorithm can handle visual drift more
      effectively and efficiently than the existing MIL tracker. We present an online
      discriminative feature selection algorithm that optimizes the objective function
      in the steepest ascent direction with respect to the positive samples while in
      the steepest descent direction with respect to the negative ones. Therefore, the
      trained classifier directly couples its score with the importance of samples,
      leading to a more robust and efficient tracker. Numerous experimental evaluations
      with state-of-the-art algorithms on challenging sequences demonstrate the merits
      of the proposed algorithm. 

PMID- 23955751
TI  - 2-Step scalar deadzone quantization for bitplane image coding.
AB  - Modern lossy image coding systems generate a quality progressive codestream that,
      truncated at increasing rates, produces an image with decreasing distortion.
      Quality progressivity is commonly provided by an embedded quantizer that employs
      uniform scalar deadzone quantization (USDQ) together with a bitplane coding
      strategy. This paper introduces a 2-step scalar deadzone quantization (2SDQ)
      scheme that achieves same coding performance as that of USDQ while reducing the
      coding passes and the emitted symbols of the bitplane coding engine. This serves
      to reduce the computational costs of the codec and/or to code high dynamic range
      images. The main insights behind 2SDQ are the use of two quantization step sizes
      that approximate wavelet coefficients with more or less precision depending on
      their density, and a rate-distortion optimization technique that adjusts the
      distortion decreases produced when coding 2SDQ indexes. The integration of 2SDQ
      in current codecs is straightforward. The applicability and efficiency of 2SDQ
      are demonstrated within the framework of JPEG2000. 

PMID- 23955752
TI  - Nonlocal hierarchical dictionary learning using wavelets for image denoising.
AB  - Exploiting the sparsity within representation models for images is critical for
      image denoising. The best currently available denoising methods take advantage of
      the sparsity from image self-similarity, pre-learned, and fixed representations.
      Most of these methods, however, still have difficulties in tackling high noise
      levels or noise models other than Gaussian. In this paper, the multiresolution
      structure and sparsity of wavelets are employed by nonlocal dictionary learning
      in each decomposition level of the wavelets. Experimental results show that our
      proposed method outperforms two state-of-the-art image denoising algorithms on
      higher noise levels. Furthermore, our approach is more adaptive to the less
      extensively researched uniform noise. 

PMID- 23955753
TI  - Blind detection of median filtering in digital images: a difference domain based
      approach.
AB  - Recently, the median filtering (MF) detector as a forensic tool for the recovery
      of images' processing history has attracted wide interest. This paper presents a
      novel method for the blind detection of MF in digital images. Following some
      strongly indicative analyses in the difference domain of images, we introduce two
      new feature sets that allow us to distinguish a median-filtered image from an
      untouched image or average-filtered one. The effectiveness of the proposed
      features is verified with evidence from exhaustive experiments on a large
      composite image database. Compared with prior arts, the proposed method achieves
      significant performance improvement in the case of low resolution and strong JPEG
      post-compression. In addition, it is demonstrated that our method is more robust
      against additive noise than other existing MF detectors. With analyses and
      extensive experimental researches presented in this paper, we hope that the
      proposed method will add a new tool to the arsenal of forensic analysts. 

PMID- 23955754
TI  - Label transfer by measuring compactness.
AB  - This paper presents a new automatic image annotation algorithm. First, we
      introduce a new similarity measure between images: compactness. This uses low
      level visual descriptors for determining the similarity between two images.
      Compactness shows how close test image features lie to training image feature
      cluster centers. The measure provides the core for a k-nearest neighbor type
      image annotation method. Afterward, a formalism for defining different transfer
      techniques is devised and several label transfer techniques are provided. The
      method as whole is evaluated on four image annotation benchmarks. The results on
      these sets validate the accuracy of the approach, which outperforms many state-of
      the-art annotation methods. The method presented here requires a simple training
      process, efficiently combines different feature types and performs better than
      complex learning algorithms, even in this incipient form. The main contributions
      of this paper are the usage of compactness as a similarity measure that enables
      efficient low level feature comparison and an annotation algorithm based on label
      transfer. 

PMID- 23955755
TI  - Efficient algorithms for robust recovery of images from compressed data.
AB  - Compressed sensing (CS) is an important theory for sub-Nyquist sampling and
      recovery of compressible data. Recently, it has been extended to cope with the
      case where corruption to the CS data is modeled as impulsive noise. The new
      formulation, termed as robust CS, combines robust statistics and CS into a single
      framework to suppress outliers in the CS recovery. To solve the newly formulated
      robust CS problem, a scheme that iteratively solves a number of CS problems--the
      solutions from which provably converge to the true robust CS solution--is
      suggested. This scheme is, however, rather inefficient as it has to use existing
      CS solvers as a proxy. To overcome limitations with the original robust CS
      algorithm, we propose in this paper more computationally efficient algorithms by
      following latest advances in large-scale convex optimization for nonsmooth
      regularization. Furthermore, we also extend the robust CS formulation to various
      settings, including additional affine constraints, l1-norm loss function, mix
      norm regularization, and multitasking, so as to further improve robust CS and
      derive simple but effective algorithms to solve these extensions. We demonstrate
      that the new algorithms provide much better computational advantage over the
      original robust CS method on the original robust CS formulation, and effectively
      solve more sophisticated extensions where the original methods simply cannot. We
      demonstrate the usefulness of the extensions on several imaging tasks.

PMID- 23955756
TI  - Image reconstruction from finite number of projections: method of transferring
      geometry.
AB  - This paper introduces a novel method of image reconstruction from a finite number
      of projections by processing the image along parallel rays. The geometry from the
      image plane is transferred to the Cartesian lattice by means of using the
      original image's line-integrals to calculate the line-sums of the discrete image
      to be reconstructed. Such a transformation of geometry allows for the 2D discrete
      paired transform, whose complete set of functions is defined by directions, to be
      effectively used in the exact reconstruction of the original image. The model of
      image reconstruction is described, and both examples and experimental results of
      implementation of the proposed method are provided for reconstruction on the
      Cartesian lattice of size 2(r) * 2(r), where r >= 2.

PMID- 23955757
TI  - A speed-up scheme based on multiple-instance pruning for pedestrian detection
      using a support vector machine.
AB  - In pedestrian detection, as sophisticated feature descriptors are used for
      improving detection accuracy, its processing speed becomes a critical issue. In
      this paper, we propose a novel speed-up scheme based on multiple-instance pruning
      (MIP), one of the soft cascade methods, to enhance the processing speed of
      support vector machine (SVM) classifiers. Our scheme mainly consists of three
      steps. First, we regularly split an SVM classifier into multiple parts and build
      a cascade structure using them. Next, we rearrange the cascade structure for
      enhancing the rejection rate, and then train the rejection threshold of each
      stage composing the cascade structure using the MIP. To verify the validity of
      our scheme, we apply it to a pedestrian classifier using co-occurrence histograms
      of oriented gradients trained by an SVM, and experimental results show that the
      processing time for classification of the proposed scheme is as low as one
      hundredth of the original classifier without sacrificing detection accuracy. 

PMID- 23955758
TI  - Fast and robust 2D-shape extraction using discrete-point sampling and centerline
      grouping in complex images.
AB  - This paper initially develops the discrete-point sampling operator's concept,
      model, and parameters that we have previously proposed, and makes its belt-shaped
      regions in a discrete-point sampling map more salient and appropriate for
      centerline extraction. The cross-sectional features of these belt-shaped regions
      are then analyzed and seven types of feature points are defined to facilitate
      descriptions of such features. Based on these feature points, a three-level
      detection system is proposed, including feature points, line segments, and
      centerlines, to extract centerlines from the belt-shaped regions. Eight basic
      types of centerlines and five types of relationships among the centerlines are
      defined by computational geometry algorithms, and Gestalt laws are used to
      cluster them into groupings. If some prior information about a desired shape is
      available, retrieval grouping may be carried out by a discrete-point sampling
      map, the purpose of which is to find centerlines by best matching with prior
      information. Discrete-point sampling effectually overcomes the influences of
      interference from noise, textures, and uneven illumination, and greatly reduces
      the difficulty of centerline extraction. Centerline clustered groupings and
      retrieval grouping can offer a strong anti-interference ability with nonlinear
      deformations such as articulation and occlusion. This method can extract large
      scale complex shapes combined of lines and planes from complex images. The wheel
      location results of noise test and other shape extraction experiments show that
      our method has a strong capability to persist with nonlinear deformations. 

PMID- 23955759
TI  - Learning component-level sparse representation for image and video
      categorization.
AB  - A novel component-level dictionary learning framework that exploits image/video
      group characteristics based on sparse representation is introduced in this paper.
      Unlike the previous methods that select the dictionaries to best reconstruct the
      data, we present an energy minimization formulation that jointly optimizes the
      learning of both sparse dictionary and component-level importance within one
      unified framework to provide a discriminative and sparse representation for
      image/video groups. The importance measures how well each feature component
      represents the group property with the dictionary. Then, the dictionary is
      updated iteratively to reduce the influence of unimportant components, thus
      refining the sparse representation for each group. In the end, by keeping the top
      K important components, a compact representation is obtained for the sparse
      coding dictionary. Experimental results on several public image and video data
      sets are shown to demonstrate the superior performance of the proposed algorithm
      compared with the-state-of-the-art methods. 

PMID- 23955760
TI  - Multilevel image thresholding based on 2D histogram and maximum Tsallis entropy-
      a differential evolution approach.
AB  - Multilevel thresholding amounts to segmenting a gray-level image into several
      distinct regions. This paper presents a 2D histogram based multilevel
      thresholding approach to improve the separation between objects. Recent studies
      indicate that the results obtained with 2D histogram oriented approaches are
      superior to those obtained with 1D histogram based techniques in the context of
      bi-level thresholding. Here, a method to incorporate 2D histogram related
      information for generalized multilevel thresholding is proposed using the maximum
      Tsallis entropy. Differential evolution (DE), a simple yet efficient evolutionary
      algorithm of current interest, is employed to improve the computational
      efficiency of the proposed method. The performance of DE is investigated
      extensively through comparison with other well-known nature inspired global
      optimization techniques such as genetic algorithm, particle swarm optimization,
      artificial bee colony, and simulated annealing. In addition, the outcome of the
      proposed method is evaluated using a well known benchmark--the Berkley
      segmentation data set (BSDS300) with 300 distinct images.

PMID- 23955761
TI  - Face recognition using ensemble string matching.
AB  - In this paper, we present a syntactic string matching approach to solve the
      frontal face recognition problem. String matching is a powerful partial matching
      technique, but is not suitable for frontal face recognition due to its
      requirement of globally sequential representation and the complex nature of human
      faces, containing discontinuous and non-sequential features. Here, we build a
      compact syntactic Stringface representation, which is an ensemble of strings. A
      novel ensemble string matching approach that can perform non-sequential string
      matching between two Stringfaces is proposed. It is invariant to the sequential
      order of strings and the direction of each string. The embedded partial matching
      mechanism enables our method to automatically use every piece of non-occluded
      region, regardless of shape, in the recognition process. The encouraging results
      demonstrate the feasibility and effectiveness of using syntactic methods for face
      recognition from a single exemplar image per person, breaking the barrier that
      prevents string matching techniques from being used for addressing complex image
      recognition problems. The proposed method not only achieved significantly better
      performance in recognizing partially occluded faces, but also showed its ability
      to perform direct matching between sketch faces and photo faces. 

PMID- 23955762
TI  - Feature adaptive co-segmentation by complexity awareness.
AB  - In this paper, we propose a novel feature adaptive co-segmentation method that
      can learn adaptive features of different image groups for accurate common objects
      segmentation. We also propose image complexity awareness for adaptive feature
      learning. In the proposed method, the original images are first ranked according
      to the image complexities that are measured by superpixel changing cue and object
      detection cue. Then, the unsupervised segments of the simple images are used to
      learn the adaptive features, which are achieved using an expectation-minimization
      algorithm combining l 1-regularized least squares optimization with the
      consideration of the confidence of the simple image segmentation accuracies and
      the fitness of the learned model. The error rate of the final co-segmentation is
      tested by the experiments on different image groups and verified to be lower than
      the existing state-of-the-art co-segmentation methods. 

PMID- 23955763
TI  - Video watermarking with empirical PCA-based decoding.
AB  - A new method for video watermarking is presented in this paper. In the proposed
      method, data are embedded in the LL subband of wavelet coefficients, and decoding
      is performed based on the comparison among the elements of the first principal
      component resulting from empirical principal component analysis (PCA). The
      locations for data embedding are selected such that they offer the most robust
      PCA-based decoding. Data are inserted in the LL subband in an adaptive manner
      based on the energy of high frequency subbands and visual saliency. Extensive
      testing was performed under various types of attacks, such as spatial attacks
      (uniform and Gaussian noise and median filtering), compression attacks (MPEG-2,
      H. 263, and H. 264), and temporal attacks (frame repetition, frame averaging,
      frame swapping, and frame rate conversion). The results show that the proposed
      method offers improved performance compared with several methods from the
      literature, especially under additive noise and compression attacks. 

PMID- 23955764
TI  - Discovering discriminative graphlets for aerial image categories recognition.
AB  - Recognizing aerial image categories is useful for scene annotation and
      surveillance. Local features have been demonstrated to be robust to image
      transformations, including occlusions and clutters. However, the geometric
      property of an aerial image (i.e., the topology and relative displacement of
      local features), which is key to discriminating aerial image categories, cannot
      be effectively represented by state-of-the-art generic visual descriptors. To
      solve this problem, we propose a recognition model that mines graphlets from
      aerial images, where graphlets are small connected subgraphs reflecting both the
      geometric property and color/texture distribution of an aerial image. More
      specifically, each aerial image is decomposed into a set of basic components
      (e.g., road and playground) and a region adjacency graph (RAG) is accordingly
      constructed to model their spatial interactions. Aerial image categories
      recognition can subsequently be casted as RAG-to-RAG matching. Based on graph
      theory, RAG-to-RAG matching is conducted by comparing all their respective
      graphlets. Because the number of graphlets is huge, we derive a manifold
      embedding algorithm to measure different-sized graphlets, after which we select
      graphlets that have highly discriminative and low redundancy topologies. Through
      quantizing the selected graphlets from each aerial image into a feature vector,
      we use support vector machine to discriminate aerial image categories.
      Experimental results indicate that our method outperforms several state-of-the
      art object/scene recognition models, and the visualized graphlets indicate that
      the discriminative patterns are discovered by our proposed approach. 

PMID- 23955765
TI  - A new automated assessment method for contrast-detail images by applying support
      vector machine and its robustness to nonlinear image processing.
AB  - The automated contrast-detail (C-D) analysis methods developed so-far cannot be
      expected to work well on images processed with nonlinear methods, such as noise
      reduction methods. Therefore, we have devised a new automated C-D analysis method
      by applying support vector machine (SVM), and tested for its robustness to
      nonlinear image processing. We acquired the CDRAD (a commercially available C-D
      test object) images at a tube voltage of 120 kV and a milliampere-second product
      (mAs) of 0.5-5.0. A partial diffusion equation based technique was used as noise
      reduction method. Three radiologists and three university students participated
      in the observer performance study. The training data for our SVM method was the
      classification data scored by the one radiologist for the CDRAD images acquired
      at 1.6 and 3.2 mAs and their noise-reduced images. We also compared the
      performance of our SVM method with the CDRAD Analyser algorithm. The mean C-D
      diagrams (that is a plot of the mean of the smallest visible hole diameter vs.
      hole depth) obtained from our devised SVM method agreed well with the ones
      averaged across the six human observers for both original and noise-reduced CDRAD
      images, whereas the mean C-D diagrams from the CDRAD Analyser algorithm disagreed
      with the ones from the human observers for both original and noise-reduced CDRAD
      images. In conclusion, our proposed SVM method for C-D analysis will work well
      for the images processed with the non-linear noise reduction method as well as
      for the original radiographic images.

PMID- 23955766
TI  - Fabrication of ZIF-8@SiO2 core-shell microspheres as the stationary phase for
      high-performance liquid chromatography.
AB  - The unique features of high porosity, shape selectivity, and multiple active
      sites make metal-organic frameworks (MOFs) promising as novel stationary phases
      for high-performance liquid chromatography (HPLC). However, the wide particle
      size distribution and irregular shape of conventional MOFs lead to lower column
      efficiency of such MOF-packed columns. Herein, the fabrication of monodisperse
      MOF@SiO2 core-shell microspheres as the stationary phase for HPLC to overcome the
      above-mentioned problems is reported. Zeolitic imidazolate framework 8 (ZIF-8)
      was used as an example of MOFs due to its permanent porosity, uniform pore size,
      and exceptional chemical stability. Unique carboxyl-modified silica spheres were
      used as the support to grow the ZIF-8 shell. The fabricated monodisperse ZIF
      8@SiO2 packed columns (5 cm long * 4.6 mm i.d.) show high column efficiency
      (23,000 plates m(-1) for bisphenol A) for the HPLC separation of endocrine
      disrupting chemicals (bisphenol A, beta-estradiol, and p-(tert-octyl)phenol) and
      pesticides (thiamethoxam, hexaflumuron, chlorantraniliprole, and pymetrozine)
      within 7 min with good relative standard deviations for 11 replicate separations
      of the analytes (0.01-0.39, 0.65-1.7, 0.70-1.3, and 0.17-0.91% for retention
      time, peak area, peak height, and half peak width, respectively). The ZIF-8@SiO2
      microspheres combine the advantages of the good column packing properties of the
      uniform monodisperse silica microspheres and the separation ability of the ZIF-8
      crystals.

PMID- 23955767
TI  - A case of infliximab-induced lupus in a patient with ankylosing spondylitis: is
      it safe switch to another anti-TNF-alpha agent?
AB  - Anti-TNF-alpha therapies are the latest class of medications found to be
      associated with drug-induced lupus, a distinctive entity known as anti-TNF-alpha
      induced lupus (ATIL) (Williams et al., Rheumatology (Oxford) 48:716-20, 2009; De
      Rycke et al., Lupus 14:931-7, 2005; De Bandt et al., Clin Rheumatol 22:56-61,
      2003). With the widespread use of these agents, it is likely that the incidence
      of ATIL will increase. The onset of ATIL in patients with rheumatoid arthritis
      and Crohn's disease has been described, but the literature regarding the
      occurrence of this entity in patients with ankylosing spondylitis (AS) is scarce
      (De Bandt et al., Clin Rheumatol 22:56-61, 2003; Ramos-Casals et al., Autoimmun
      Rev 9:188-93, 2010; Perez-Garcia et al., Rheumatology 45:114-116, 2006). To our
      knowledge, few reports of switching anti-TNF-alpha therapy after ATIL in AS have
      been reported (Akgul et al., Rheumatol Int, 2012). Therefore, it is not clear
      whether the development of ATIL should prohibit switch to another therapy, since
      patients may respond to another anti-TNF-alpha agent (Akgul et al., Rheumatol
      Int, 2012; Bodur et al., Rheumatol Int 29:451-454, 2009; Mounach et al., Clin Exp
      Rheumatol 26:1116-8, 2008; Williams and Cohen, Int J Dermatol 50:619-625, 2011;
      Ye et al., J Rheumatol 38:1216, 2011; Wetter and Davis, Mayo Clin Proc 84:979
      984, 2009; Cush, Clin Exp Rheumatol 22:S141-147, 2004; Kocharla and Mongey, Lupus
      18:169-7, 2009). A lack of published experience of successful anti-TNF-alpha
      switching is a cause of concern for rheumatologists faced with this challenging
      clinical scenario. We report the case of a 69-year-old woman with AS who
      developed infliximab-induced lupus, which did not recur despite the subsequent
      institution of etanercept. The authors review and discuss ATIL and the possible
      implications for subsequent treatment with alternative anti-TNF-alpha agents. 

PMID- 23955768
TI  - The Ludloff osteotomy: a review of current concepts.
AB  - The Ludloff osteotomy is a technique option to address hallux valgus in patients
      with a moderately to significantly increased first-second intermetatarsal angle.
      The Ludloff osteotomy is an oblique osteotomy of the first metatarsal extending
      dorsal-proximal to plantar-distal when viewed in the sagittal plane. The dorsal
      proximal portion of the metatarsal is cut with the saw while maintaining the
      plantar-distal surface intact. A screw is inserted across the proximal aspect of
      the osteotomy, then the osteotomy is extended across the plantar surface
      distally. The metatarsal is rotated around the axis of the screw to the desired
      correction. In order to perform the osteotomy correctly, the surgeon must not
      only effectively complete the nuances of the technique, but also understand the
      limitations and contraindications of the Ludloff osteotomy. This review of
      current concepts for the Ludloff osteotomy reviews recent literature as well as
      technique pearls and pitfalls in the application of this powerful osteotomy. 

PMID- 23955769
TI  - Boomerang proximal tibial osteotomy for the treatment of severe varus
      gonarthrosis.

PMID- 23955770
TI  - The common ecotoxicology laboratory strain of Hyalella azteca is genetically
      distinct from most wild strains sampled in eastern North America.
AB  - The amphipod Hyalella azteca is commonly used as a model for determining safe
      concentrations of contaminants in freshwaters. The authors sequenced the
      mitochondrial cytochrome c oxidase subunit I (COI) gene for representatives of 38
      populations of this species complex from US and Canadian toxicology research
      laboratories and eastern North American field sites to determine their genetic
      relationships. With 1 exception, all US and Canadian laboratory cultures sampled
      were identified as conspecific. In 22 wild populations spanning 5 US states and 1
      Canadian province, the commonly occurring laboratory species was found only in
      northern Florida, USA. Therefore, the diversity of the H. azteca species complex
      detected in the wild is not accurately represented in North American
      laboratories, questioning the reliability of H. azteca cultures currently in use
      to accurately predict the responses of wild populations in ecotoxicological
      assays. The authors also examined the utility of different COI nucleotide
      fragments presently in use to determine phylogenetic relationships in this group
      and concluded that saturation in DNA sequences leads to inconsistent
      relationships between clades. Amino acid sequences for COI were not saturated and
      may allow a more accurate phylogeny estimate. Hyalella azteca is crucial for
      developing water-quality regulations; therefore, laboratories should know and
      standardize the strain(s) they use to confidently compare toxicity tests across
      laboratories and determine whether they are an appropriate surrogate for their
      regions.

PMID- 23955771
TI  - Site-specific characterization of the Asp- and Glu-ADP-ribosylated proteome.
AB  - Poly(ADP-ribosyl)ation is catalyzed by a family of enzymes known as PARPs. We
      describe a method to characterize the human aspartic acid- and glutamic acid-ADP
      ribosylated proteome. We identified 1,048 ADP-ribosylation sites on 340 proteins
      involved in a wide array of nuclear functions; among these were many previously
      unknown PARP downstream targets whose ADP-ribosylation was sensitive to PARP
      inhibitor treatment. We also confirmed that iniparib had a negligible effect on
      PARP activity in intact cells. 

PMID- 23955772
TI  - UPARSE: highly accurate OTU sequences from microbial amplicon reads.
AB  - Amplified marker-gene sequences can be used to understand microbial community
      structure, but they suffer from a high level of sequencing and amplification
      artifacts. The UPARSE pipeline reports operational taxonomic unit (OTU) sequences
      with <=1% incorrect bases in artificial microbial community tests, compared with
      >3% incorrect bases commonly reported by other methods. The improved accuracy
      results in far fewer OTUs, consistently closer to the expected number of species
      in a community. 

PMID- 23955774
TI  - Best practices for evaluating mutation prediction methods.

PMID- 23955773
TI  - Recombinant antibodies to histone post-translational modifications.
AB  - Variability in the quality of antibodies to histone post-translational
      modifications (PTMs) is a widely recognized hindrance in epigenetics research.
      Here, we produced recombinant antibodies to the trimethylated lysine residues of
      histone H3 with high specificity and affinity and no lot-to-lot variation. These
      recombinant antibodies performed well in common epigenetics applications, and
      enabled us to identify positive and negative correlations among histone PTMs. 

PMID- 23955775
TI  - Hypersomnolence and reduced activity in pan-leptin receptor knockout mice.
AB  - Excessive obesity correlates with hypersomnolence and impaired cognitive
      function, presumably induced by metabolic factors and cytokines. Production of
      the adipokine leptin correlates with the amount of adiposity, and leptin has been
      shown to promote sleep. To determine whether leptin plays a major role in the
      hypersomnolence of obesity, we measured sleep architecture in pan-leptin receptor
      knockout (POKO) mice that do not respond to leptin because of the production of a
      mutant, non-signaling receptor. The obese POKO mice had more non-rapid eye
      movement (NREM) sleep and less waking time than their littermate controls. This
      was mainly seen during the light span, although increased bouts of rapid eye
      movement sleep were also seen in the dark span. The increase of NREM sleep
      correlated with the extent of obesity. The POKO mice also had decreased locomotor
      activity and more immobility in the open field test, but there was no increase of
      forced immobility nor reduction of sucrose intake as would be seen in depression.
      The increased NREM sleep and reduced locomotor activity in the POKO mice suggest
      that it was obesity, rather than leptin signaling, that played a predominant role
      in altering sleep architecture and activity. 

PMID- 23955776
TI  - Predicting interacting residues using long-distance information and novel
      decoding in hidden Markov models.
AB  - Identification of interacting residues involved in protein-protein and protein
      ligand interaction is critical for the prediction and understanding of the
      interaction and has practical impact on mutagenesis and drug design. In this
      work, we introduce a new decoding algorithm, ETB-Viterbi, with an early traceback
      mechanism, and apply it to interaction profile hidden Markov models (ipHMMs) to
      enable optimized incorporation of long-distance correlations between interacting
      residues, leading to improved prediction accuracy. The method was applied and
      tested to a set of domain-domain interaction families from the 3DID database, and
      showed statistically significant improvement in accuracy measured by F-score. To
      gauge and assess the method's effectiveness and robustness in capturing the
      correlation signals, sets of simulated data based on the 3DID dataset with
      controllable correlation between interacting residues were also used, as well as
      reversed sequence orientation. It was demonstrated that the prediction
      consistently improves as the correlations increase and is not significantly
      affected by sequence orientation.

PMID- 23955778
TI  - Optical capsule and tweezer array for molecular motor use.
AB  - A generation of optical capsules and tweezers within a modified optical add-drop
      filter known as PANDA ring resonator with a new concept is proposed. By using
      dark and bright solitons, the orthogonal tweezers can be formed within the system
      and observed simultaneously at the output ports. Under the resonant condition,
      the optical capsules and tweezers generated by dark and bright soliton pair
      corresponding to the left-hand and right-hand rotating solitons (tweezers) can be
      generated. When a soliton is interacted by an object, an angular momentum of
      either bright or dark tweezers is imparted to the object, in which two possible
      spin states known as tweezer spins are exhibited. Furthermore, an array of
      molecular capsules and spins, i.e., trapped molecules can be generated and
      detected by using the proposed system, which can be used to form large scale
      tweezer or capsule spins. In application, the trapped molecules can be moved and
      rotated securely to the required destinations, which can be useful for many
      applications, especially, in medical diagnosis, therapy and surgery.

PMID- 23955777
TI  - A Local Poisson Graphical Model for inferring networks from sequencing data.
AB  - Gaussian graphical models, a class of undirected graphs or Markov Networks, are
      often used to infer gene networks based on microarray expression data. Many
      scientists, however, have begun using high-throughput sequencing technologies
      such as RNA-sequencing or next generation sequencing to measure gene expression.
      As the resulting data consists of counts of sequencing reads for each gene,
      Gaussian graphical models are not optimal for this discrete data. In this paper,
      we propose a novel method for inferring gene networks from sequencing data: the
      Local Poisson Graphical Model. Our model assumes a Local Markov property where
      each variable conditional on all other variables is Poisson distributed. We
      develop a neighborhood selection algorithm to fit our model locally by performing
      a series of l1 penalized Poisson, or log-linear, regressions. This yields a fast
      parallel algorithm for estimating networks from next generation sequencing data.
      In simulations, we illustrate the effectiveness of our methods for recovering
      network structure from count data. A case study on breast cancer microRNAs
      (miRNAs), a novel application of graphical models, finds known regulators of
      breast cancer genes and discovers novel miRNA clusters and hubs that are targets
      for future research.

PMID- 23955779
TI  - Multistability and its robustness of a class of biological systems.
AB  - Multistability of biological systems with complex nonlinear regulatory schemes is
      an important research topic in system biology. In many models of biological
      systems, the regulatory functions are of saturation type. The linear sectors, in
      which the saturation type functions reside, have been extensively adopted to deal
      with these saturation type functions. The stability analysis resulting from
      linear sectors is however often conservative as a wide linear section is required
      to include a large portion of a saturation type function. In this paper, we
      utilize piecewise linear sectors, recently adopted in nonlinear control theory,
      to investigate multistability of a class of biological systems with sum
      regulatory schemes. We will estimate the domain of attraction of each stable
      equilibrium and examine the robust stability of each equilibrium in the face of
      disturbances that are bounded in magnitude or energy. A genetic toggle switch in
      Escherichia coli is employed as an example to illustrate the applicability and
      effectiveness of our analysis method.

PMID- 23955780
TI  - In vitro and in vivo imaging of peptide-encapsulated polymer nanoparticles for
      cancer biomarker activated drug delivery.
AB  - Gelatin nanoparticles coated with Cathepsin D-specific peptides were developed as
      a vehicle for the targeted delivery of the cancer drug doxorubicin (DOX) to treat
      breast malignancy. Cathepsin D, a breast cancer cell secretion enzyme, triggered
      the release of DOX by digesting the protective peptide-coating layer of
      nanoparticles. Fabricated nanoparticles were successfully detected with
      ultrasound imaging in both in vitro conditions and in vivo mouse cancer models.
      Cell viability experiments were conducted to determine the efficacy of biomarker
      activation specific to breast cancer cell lines. These experimental results were
      compared with the outcome of a viability experiment conducted on noncancerous
      cells. Viability decreased in human MCF7 mammary adenocarcinoma and mouse 4T1
      mammary carcinoma cells, while that of noncancerous 3T3 fibroblast cells remained
      unaffected. Next, a real-time video of nanoparticle flow in mouse models was
      obtained using in vivo ultrasound imaging. The fluorescent profile of DOX was
      used as a means to examine nanoparticle localization in vivo. Results show the
      distribution of nanoparticles concentrated primarily within bladder and tumor
      sites of subject mice bodies. These findings support the use of biomarker coated
      nanoparticles in target specific therapy for breast cancer treatment.

PMID- 23955781
TI  - GRtoGR: a system for mapping GO relations to gene relations.
AB  - We introduce in this paper a biological search engine called GRtoGR. Given a set
      of S genes, GRtoGR would determine from GO graph the most significant Lowest
      Common Ancestor (LCA) of the GO terms annotating the set S. This significant LCA
      annotates the genes that are the most semantically related to the set S. The
      framework of GRtoGR refines the concept of LCA by introducing the concepts of
      Relevant Lowest Common Ancestor (RLCA) and Semantically Relevant Lowest Common
      Ancestor (SRLCA). A SRLCA is the most significant LCA of the GO terms annotating
      the set S. We observe that the existence of the GO terms annotating the set S is
      dependent on the existence of this SRLCA in GO graph. That is, the terms
      annotating a given set of genes usually have existence dependency relationships
      with the SRLCA of these terms. We evaluated GRtoGR experimentally and compared it
      with nine other methods. Results showed marked improvement.

PMID- 23955783
TI  - The obesity pattern of idiopathic intracranial hypertension in men.
AB  - BACKGROUND: Idiopathic intracranial hypertension (IIH), also known as pseudotumor
      cerebri, is a disorder of unknown etiology, predominantly affecting obese women
      of childbearing age. IIH is uncommon in men, with a reported female-to-male ratio
      of 8:1. The pathogenesis of IIH is poorly understood. Several mechanisms have
      been suggested, but no one mechanism has been able to account for all
      manifestations of the disease. This research aims to characterize the obesity
      phenotype(s) of men with IIH in order to find potential inducers for this
      disease. METHODS: This is a cross-sectional study based on subjects' medical
      records. It compared anthropometric parameters between 22 men with IIH, 60
      healthy men, and 44 females with IIH. One-way analysis with age and body mass
      index included as covariates was applied for the assessment of the difference in
      fat distribution among the three groups. RESULTS: No significant differences were
      observed between the male IIH cohort and healthy males for age, BMI, and waist
      measurements, whereas hip circumference was significantly larger in the IIH
      cohort (114 +/- 13 vs. 104 +/- 16 cm; respectively, p < 0.001). Consequently,
      waist-to-hip ratio (WHR) was significantly lower in the male IIH cohort (0.88 +/-
      0.08 vs. 0.95 +/- 0.12; p < 0.001). While no significant differences were
      observed for age and hip measurements between male IIH and female IIH cohorts,
      waist circumference and waist-to-hip ratio (WHR) were significantly larger in the
      male cohort (102 +/- 19 cm vs. 95 +/- 13 cm, p < 0.001; 0.88 +/- 0.08 vs. 0.78 +/
      0.06, p < 0.001, respectively). All these results maintained after adjustment
      for age and BMI. CONCLUSIONS: This is the first report of body fat distribution
      patterns in men with IIH. Whereas male IIH have larger central fat deposition
      than female IIH patients, abdominal fatness is less accentuated in IIH men
      compared to normal obese men. The later observation is in agreement with similar
      results regarding female IIH patients. We believe that these findings justify
      further investigation into the involvement of various fat depots in the
      pathogenesis of IIH in men and women alike.

PMID- 23955786
TI  - The importance of clinical pathways and protocols in pediatric nephrology.
AB  - Modern clinical practice is increasingly delivered by teams of individuals
      working within an environment of rising complexity and daunting patient care
      loads. Clinical pathways, protocols and checklists offer a way to assure
      coordination, efficiency, quality and safety in this chaotic environment. In this
      review, we discuss some of the principal characteristics of these clinical tools,
      some of the challenges involved with introducing them into clinical practice and
      the evidence that they can positively affect patient and system outcomes. We
      believe pediatric nephrology, as a discipline, is ready for the widespread
      introduction of these important quality tools. 

PMID- 23955787
TI  - Quality of life in adult congenital heart disease: what do we already know and
      what do we still need to know?
AB  - Quality of life (QOL) is a key outcome in patients with congenital heart disease
      (CHD) because CHD has become a chronic condition accompanied by lifelong
      impairments. Recently, published studies on QOL in adults with CHD have reported
      inconsistent findings. Patients' QOL seems to depend on multiple factors and is
      not solely determined by their heart defect and various medical or demographic
      characteristics. For instance, evidence suggests that a strong sense of coherence
      might be an important pathway to improve QOL. However, studies on QOL and its
      determinants are characterized by important methodological differences and
      limitations, making it impossible to draw firm conclusions. To fill the gaps in
      the current evidence base, longitudinal and international research is needed.
      Furthermore, the research field on QOL in CHD should move on from observational
      studies to interventional research to guide health professionals in improving
      QOL. 

PMID- 23955789
TI  - Design of a Programmable Gain, Temperature Compensated Current-Input Current
      Output CMOS Logarithmic Amplifier.
AB  - This paper presents the design of a programmable gain, temperature compensated,
      current-mode CMOS logarithmic amplifier that can be used for biomedical signal
      processing. Unlike conventional logarithmic amplifiers that use a transimpedance
      technique to generate a voltage signal as a logarithmic function of the input
      current, the proposed approach directly produces a current output as a
      logarithmic function of the input current. Also, unlike a conventional
      transimpedance amplifier the gain of the proposed logarithmic amplifier can be
      programmed using floating-gate trimming circuits. The synthesis of the proposed
      circuit is based on the Hart's extended translinear principle which involves
      embedding a floating-voltage source and a linear resistive element within a
      translinear loop. Temperature compensation is then achieved using a translinear
      based resistive cancelation technique. Measured results from prototypes
      fabricated in a 0.5 MUm CMOS process show that the amplifier has an input dynamic
      range of 120 dB and a temperature sensitivity of 230 ppm/ degrees C (27  degrees
      C- 57 degrees C), while consuming less than 100 nW of power.

PMID- 23955784
TI  - Mobility of photosynthetic proteins.
AB  - The mobility of photosynthetic proteins represents an important factor that
      affects light-energy conversion in photosynthesis. The specific feature of
      photosynthetic proteins mobility can be currently measured in vivo using advanced
      microscopic methods, such as fluorescence recovery after photobleaching which
      allows the direct observation of photosynthetic proteins mobility on a single
      cell level. The heterogeneous organization of thylakoid membrane proteins results
      in heterogeneity in protein mobility. The thylakoid membrane contains both,
      protein-crowded compartments with immobile proteins and fluid areas (less crowded
      by proteins), allowing restricted diffusion of proteins. This heterogeneity
      represents an optimal balance as protein crowding is necessary for efficient
      light-energy conversion, and protein mobility plays an important role in the
      regulation of photosynthesis. The mobility is required for an optimal light
      harvesting process (e.g., during state transitions), and also for transport of
      proteins during their synthesis or repair. Protein crowding is then a key
      limiting factor of thylakoid membrane protein mobility; the less thylakoid
      membranes are crowded by proteins, the higher protein mobility is observed.
      Mobility of photosynthetic proteins outside the thylakoid membrane (lumen and
      stroma/cytosol) is less understood. Cyanobacterial phycobilisomes attached to the
      stromal side of the thylakoid can move relatively fast. Therefore, it seems that
      stroma with their active enzymes of the Calvin-Benson cycle, are a more fluid
      compartment in comparison to the rather rigid thylakoid lumen. In conclusion,
      photosynthetic protein diffusion is generally slower in comparison to similarly
      sized proteins from other eukaryotic membranes or organelles. Mobility of
      photosynthetic proteins resembles restricted protein diffusion in bacteria, and
      has been rationalized by high protein crowding similar to that of thylakoids. 

PMID- 23955788
TI  - Stem cell therapy for electrophysiological disorders.
AB  - Cardiovascular diseases are a leading cause of mortality worldwide. Terminally
      differentiated adult cardiomyocytes lack the innate ability to regenerate. Cell-
      and gene-based therapies are emerging as exciting new experimental strategies for
      myocardial repair and treatment of a variety of cardiovascular diseases. The
      potential advantages and shortcomings of each strategy for electrophysiological
      disorders are discussed. Since the first description of human induced pluripotent
      stem cell-derived cardiomyocytes, these cells have garnered tremendous interest
      for their potential use in patient-specific analysis and therapy. However, a full
      understanding of their electrophysiological and contractile function is necessary
      before this potential can be realized. This review focuses on the mechanisms by
      which stem cell therapy may function as an antiarrhythmic treatment and early
      clinical results. 

PMID- 23955790
TI  - Targeting monocarboxylate transporter by alpha-cyano-4-hydroxycinnamate modulates
      apoptosis and cisplatin resistance of Colo205 cells: implication of altered cell
      survival regulation.
AB  - The present investigation was undertaken to study the effect of in vitro exposure
      of Colo205, colonadenocarcinoma cells, to monocarboxylate transporter inhibitor
      alpha-cyano-4-hydroxycinnamate (alphaCHC) on cell survival and evolution of
      resistance to chemotherapeutic drug cisplatin. alphaCHC-treated Colo205 cells
      showed inhibition of survival accompanied by an augmented induction of apoptosis.
      Changes in cell survival properties were associated with alterations in lactate
      efflux, pH homeostasis, expression of glucose transporters, glucose uptake, HIF
      1alpha, generation of nitric oxide, expression pattern of some key cell survival
      regulatory molecules: Bcl2, Bax, active caspase-3 and p53. Pretreatment of
      Colo205 cells with alphaCHC also altered their susceptibility to the cytotoxicity
      of cisplatin accompanied by altered expression of multidrug resistance regulating
      MDR1 and MRP1 genes. This study for the first time deciphers some of the key
      molecular events underlying modulation of cell survival of cancer cells of
      colorectal origin by alphaCHC and its contribution to chemosensitization against
      cisplatin. Thus these findings will be of immense help in further research for
      optimizing the use of alphaCHC for improving the chemotherapeutic efficacy of
      anticancer drugs like cisplatin. 

PMID- 23955791
TI  - Three-week inpatient Cognitive Evolutionary Therapy (CET) for patients with
      personality disorders: evidence of effectiveness in symptoms reduction and
      improved treatment adherence.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy of Cognitive
      Evolutionary Therapy (CET) in an intensive short residential treatment of a wide
      range of severe personality disorders (PDs) that resulted in a reduction of
      social functioning and significant personal distress. DESIGN: Each patient was
      assessed at admission, discharge, and 3 months later in order to determine if
      there was a reduction in symptoms and an improved adherence to former outpatient
      programs and to check if patients were undergoing new treatment after discharge.
      METHOD: Fifty-one patients participated in this study. The 20-hr weekly program
      consisted of two individual sessions and various group modules. Outcome measures
      included: self-reported measures of depression, anxiety, general symptoms, number
      and duration of inpatient admissions after the programme, and continuation in an
      outpatient treatment programme. RESULTS: The results show an overall improvement
      in general psychopathology after the release and in follow-up sessions, a
      decrease in the number of further hospital admissions, and an increased level of
      attendance of outpatient therapy. CONCLUSIONS: This study shows that intensive
      short residential treatment is an effective treatment for patients with a wide
      range of PDs.

PMID- 23955792
TI  - How collaboration in therapy becomes therapeutic: the therapeutic collaboration
      coding system.
AB  - BACKGROUND: The quality and strength of the therapeutic collaboration, the core
      of the alliance, is reliably associated with positive therapy outcomes. The
      urgent challenge for clinicians and researchers is constructing a conceptual
      framework to integrate the dialectical work that fosters collaboration, with a
      model of how clients make progress in therapy. AIM: We propose a conceptual
      account of how collaboration in therapy becomes therapeutic. In addition, we
      report on the construction of a coding system - the therapeutic collaboration
      coding system (TCCS) - designed to analyse and track on a moment-by-moment basis
      the interaction between therapist and client. Preliminary evidence is presented
      regarding the coding system's psychometric properties. The TCCS evaluates each
      speaking turn and assesses whether and how therapists are working within the
      client's therapeutic zone of proximal development, defined as the space between
      the client's actual therapeutic developmental level and their potential
      developmental level that can be reached in collaboration with the therapist.
      METHOD: We applied the TCCS to five cases: a good and a poor outcome case of
      narrative therapy, a good and a poor outcome case of cognitive-behavioural
      therapy, and a dropout case of narrative therapy. CONCLUSION: The TCCS offers
      markers that may help researchers better understand the therapeutic collaboration
      on a moment-to-moment basis and may help therapists better regulate the
      relationship.

PMID- 23955793
TI  - Conceptualizing the therapist's role in therapy in psychosis.
AB  - OBJECTIVES: This paper reports on a subset of findings from a wider ranging
      grounded theory analysis of therapy and recovery processes in psychosis. It
      describes therapist activities involved in maintaining an observational
      perspective during therapy and the links between these and other therapist
      activities. DESIGN: Grounded theory was used to examine the qualitative data
      collected. METHODS: An initial sample of 19 taped therapy sessions and 23
      interviews with psychologists and their clients was collected. This sample was
      extended through the collection of three further interviews with
      psychoanalytically aware psychologists. The data were analysed using grounded
      theory. RESULTS: A grounded theory model of therapy processes in psychosis was
      developed that conceptualized therapist actions as providing an observational
      scaffold to support the client's efforts in moving to new perspectives on their
      situation. Consistent with the understanding of the core therapy activity as a
      dialogical process, this set of therapist actions was understood as occurring
      alongside other therapist activities involved in managing emotion and building a
      relationship in therapy. CONCLUSIONS: The central activity of therapy in
      psychosis was understood as a dialogical process continuously negotiated between
      therapist and client in conversation and was conceptually summarized in the
      grounded theory as 'building bridges to observational perspectives'. However, the
      active and strategic efforts of psychologists to sustain the dialogue implied a
      particular assumption of responsibility for maintaining this process. In
      particular, therapists appeared to be 'working to maintain observational
      perspectives', 'managing emotion', and 'doing relationship' during the therapy
      conversation as part of the joint effort with clients to build bridges to new
      observational perspectives on distress and psychosis.

PMID- 23955794
TI  - Comfort and challenge: a thematic analysis of female clinicians' experiences of
      supervision.
AB  - OBJECTIVE: The supervision of counsellors, counselling psychologists, and
      psychotherapists is generally perceived to be an invaluable component of training
      and practice. The present study analysed this process to explore the meanings of
      supervision and to consider implications for clinical practice and training.
      DESIGN: This study presents the accounts of 19 psychological therapists who
      experienced supervision while working at a London-based women's therapy centre.
      METHOD: Demographic information was collected by questionnaire, and semi
      structured interviews were conducted to explore aspects of the supervisory
      experience. The qualitative data were thematically analysed. RESULTS: Supervision
      has complex and paradoxical meanings, and it impacts on clinical counselling
      practice in multifarious ways. Dominant themes highlighted were the usefulness of
      supervision, specifically support, empowerment, and joining; fear of exposure in
      supervision versus gaining new information; the comfort versus the challenge of
      supervision; and supervision as a containing space. CONCLUSIONS: An experiential
      model of supervision was developed from the data. This model complements existing
      models in the field. It could be evaluated and used alongside existing models in
      various training and supervision contexts. Findings are discussed in relation to
      the literature on clinical supervision.

PMID- 23955795
TI  - 3-D rigid body tracking using vision and depth sensors.
AB  - In robotics and augmented reality applications, model-based 3-D tracking of rigid
      objects is generally required. With the help of accurate pose estimates, it is
      required to increase reliability and decrease jitter in total. Among many
      solutions of pose estimation in the literature, pure vision-based 3-D trackers
      require either manual initializations or offline training stages. On the other
      hand, trackers relying on pure depth sensors are not suitable for AR
      applications. An automated 3-D tracking algorithm, which is based on fusion of
      vision and depth sensors via extended Kalman filter, is proposed in this paper. A
      novel measurement-tracking scheme, which is based on estimation of optical flow
      using intensity and shape index map data of 3-D point cloud, increases 2-D, as
      well as 3-D, tracking performance significantly. The proposed method requires
      neither manual initialization of pose nor offline training, while enabling highly
      accurate 3-D tracking. The accuracy of the proposed method is tested against a
      number of conventional techniques, and a superior performance is clearly observed
      in terms of both objectively via error metrics and subjectively for the rendered
      scenes. 

PMID- 23955796
TI  - Monocular 3-D gait tracking in surveillance scenes.
AB  - Gait recognition can potentially provide a noninvasive and effective biometric
      authentication from a distance. However, the performance of gait recognition
      systems will suffer in real surveillance scenarios with multiple interacting
      individuals and where the camera is usually placed at a significant angle and
      distance from the floor. We present a methodology for view-invariant monocular 3
      D human pose tracking in man-made environments in which we assume that observed
      people move on a known ground plane. First, we model 3-D body poses and camera
      viewpoints with a low dimensional manifold and learn a generative model of the
      silhouette from this manifold to a reduced set of training views. During the
      online stage, 3-D body poses are tracked using recursive Bayesian sampling
      conducted jointly over the scene's ground plane and the pose-viewpoint manifold.
      For each sample, the homography that relates the corresponding training plane to
      the image points is calculated using the dominant 3-D directions of the scene,
      the sampled location on the ground plane and the sampled camera view. Each
      regressed silhouette shape is projected using this homographic transformation and
      is matched in the image to estimate its likelihood. Our framework is able to
      track 3-D human walking poses in a 3-D environment exploring only a 4-D state
      space with success. In our experimental evaluation, we demonstrate the
      significant improvements of the homographic alignment over a commonly used
      similarity transformation and provide quantitative pose tracking results for the
      monocular sequences with a high perspective effect from the CAVIAR dataset. 

PMID- 23955797
TI  - Computer vision for RGB-D sensors: Kinect and its applications.
AB  - Kinect sensor, high-resolution depth and visual (RGB) sensing has become
      available for widespread use as an off-the-shelf technology. This special issue
      is specifically dedicated to new algorithms and/or new applications based on the
      Kinect (or similar RGB-D) sensors. In total, we received over ninety submissions
      from more than twenty countries all around the world. The submissions cover a
      wide range of areas including object and scene classification, 3-D pose
      estimation, visual tracking, data fusion, human action/activity recognition, 3-D
      reconstruction, mobile robotics, and so on. After two rounds of review by at
      least two (mostly three) expert reviewers for each paper, the Guest Editors have
      selected twelve high-quality papers to be included in this highly popular special
      issue. The papers that comprise this issue are briefly summarized. 

PMID- 23955798
TI  - Heteroleptic alkyl and amide iminoanilide alkaline earth and divalent rare earth
      complexes for the catalysis of hydrophosphination and (cyclo)hydroamination
      reactions.
AB  - [{N^N}M(X)(thf)n] alkyl (X=CH(SiMe3)2) and amide (X=N(SiMe3)2) complexes of
      alkaline earths (M=Ca, Sr, Ba) and divalent rare earths (Yb(II) and Eu(II) )
      bearing an iminoanilide ligand ({N^N}(-)) are presented. Remarkably, these
      complexes proved to be kinetically stable in solution. X-ray diffraction studies
      allowed us to establish size-structure trends. Except for one case of oxidation
      with [{N^N}Yb(II){N(SiMe3)2}(thf)], all these complexes are stable under the
      catalytic conditions and constitute effective precatalysts for the
      cyclohydroamination of terminal aminoalkenes and the intermolecular
      hydroamination and intermolecular hydrophosphination of activated alkenes. Metals
      with equal sizes across alkaline earth and rare earth families display almost
      identical apparent catalytic activity and selectivity. Hydrocarbyl complexes are
      much better catalyst precursors than their amido analogues. In the case of
      cyclohydroamination, the apparent activity decreases with metal size: Ca>Sr>Ba,
      and the kinetic rate law agrees with R(CHA) =k[precatalyst](1)[aminoalkene](1).
      The intermolecular hydroamination and hydrophosphination of styrene are anti
      Markovnikov regiospecific. In both cases, the apparent activity increases with
      the ionic radius (Ca<Sr<Ba) but the rate laws are different, and obey R(HA)
      =k[styrene](1)[amine](1)[precatalyst](1) and R(HP) =k[styrene](1)[HPPh2
      ](0)[precatalyst](1), respectively. Mechanisms compatible with the rate laws and
      kinetic isotopic effects are proposed. [{N^N}Ba{N(SiMe3)2}(thf)2] (3) and
      [{N^N}Ba{CH(SiMe3)2}(thf)2] (10) are the first efficient Ba-based precatalysts
      for intermolecular hydroamination and hydrophosphination, and display activity
      values that are above those reported so far. The potential of the precatalysts
      for C-N and C-P bond formation is detailed and a rare cyclohydroamination
      intermolecular hydroamination "domino" sequence is presented.

PMID- 23955799
TI  - Implications of Bit1 and AIF overexpressions in esophageal squamous cell
      carcinoma.
AB  - Overwhelming evidence has demonstrated that Bit1 and AIF as mitochondrial
      proteins are implicated in the development and progression of a variety of
      tumors. However, their expressions and biological functions in esophageal
      squamous cell carcinoma (ESCC) remain to be delineated. In the present study, we
      found that Bit1, AIF, and Bcl-2 levels in ESCC tissues were significantly higher
      than those in normal esophageal epithelial tissues and dysplasia tissues (P <
      0.05). Stepwise investigation demonstrated that Bit1 and Bcl-2 levels were both
      tightly associated with lymphatic metastasis and TNM staging (P < 0.05), and the
      levels of Bit1 mRNA as well as AIF and Bcl-2 proteins were both closely related
      to tumor differentiation (P < 0.05), but not related to the patients' age and
      gender (P > 0.05). Importantly, Bit1 mRNA and protein levels in ESCC with
      lymphatic metastasis and TNM staging in III and IV were markedly higher than that
      without lymphatic metastasis and TMN staging in I and II. Further analysis showed
      that expression of Bit1 protein was both positively correlated with expressions
      of AIF and Bcl-2 proteins (r = 0.408 and 0.405, respectively; P < 0.05).
      Correctively, our data cited earlier suggest that Bit1 plays pivotal roles in the
      development and progression of ESCC, and its biological functions in ESCC may be
      closely associated with AIF and Bcl-2 levels. 

PMID- 23955800
TI  - Association between RAD51 gene polymorphism (-135G/C) and susceptibility of
      myelodysplastic syndrome and acute leukemia: evidence based on a meta-analysis.
AB  - Study results on the association between RAD51 gene -135G/C polymorphism and risk
      of myelodysplastic syndrome (MDS) or acute leukemia are inconsistent. A meta
      analysis was conducted to identify the association. A systematic search was
      performed in PubMed, Embase, CNKI, VIP, Wanfang databases to collect all relevant
      studies until January 2013. Meta-analysis was carried out using fixed/random
      model by Review Manager 5.1 and STATA10.0. A total of 10 eligible studies with
      2,656 patients and 3,725 controls were included in meta-analysis. Significant
      association was detected between -135G/C polymorphism and increased MDS risk (CC
      + GC vs. GG: OR = 1.46, 95% CI = 1.11-1.92; CC vs. GC + GG: OR = 2.45, 95% CI =
      1.23-4.89), while no association was observed for acute leukemia. Subgroup
      analysis by subtypes of acute leukemia and ethnicity showed no significant
      results either. Our meta-analysis indicated that the -135G/C polymorphism might
      be associated with increased susceptibility of MDS. However, lack of evidence
      supported association of this polymorphism with acute leukemia. Additional well
      designed studies with larger samples are required to verify our results.

PMID- 23955801
TI  - Lack of association of EPHX1 gene polymorphisms with risk of hepatocellular
      carcinoma: a meta-analysis.
AB  - Previous studies have focused on the association of a gene (EPHX1) encoding
      microsomal epoxide hydrolase with the carcinogenesis of hepatocellular carcinoma
      (HCC). In the present study, we performed a meta-analysis to systematically
      summarize the possible association between EPHX1 genetic polymorphisms and the
      risk for HCC. We conducted a search of case-control studies on the associations
      of EPHX1 genetic polymorphisms with susceptibility to HCC in PubMed, EMBASE, ISI
      Web of Science, Wanfang database in China, and the Chinese National Knowledge
      Infrastructure databases. Data from eligible studies were extracted for meta
      analysis. HCC risk associated with EPHX1 genetic polymorphism was estimated by
      pooled odds ratios and 95% confidence intervals. Thirteen studies were included
      in the present meta-analysis. Our results showed that, for the two polymorphisms
      (337 T > C and 416A > G) of EPHX1 gene, neither allele frequency nor genotype
      distributions were associated with risk for HCC in all genetic models (all P >
      0.05). This meta-analysis suggests that EPHX1 genetic polymorphisms were not
      associated with the risk of HCC.

PMID- 23955802
TI  - The phenotype of ex vivo generated cytokine-induced killer cells is associated
      with overall survival in patients with cancer.
AB  - Cytokine-induced killer (CIK) cells are ex vivo generated heterogeneous NK-like T
      lymphocytes. It is not very clear whether the phenotype of CIK cells is
      associated with their therapeutic efficacy to cancer patients. Thus, in this
      study, the association of phenotype of CIK cells and the overall survival of 121
      patients with hepatocellular carcinoma (HCC), 74 patients with lung cancer and 42
      patients with colorectal cancer, all of whom underwent surgical resection and
      received autogenous CIK cell therapy, was analyzed. We found that high ratio of
      the CD3+CD4+ subset was associated with poorer overall survival in colorectal
      cancer, but not HCC or lung cancer. A high ratio of the CD3+CD8+ subset was
      associated with improved overall survival in all three types of cancer. A high
      ratio of the CD3+CD56+ NK-like subset was associated with improved overall
      survival in lung and colorectal cancer, but not HCC. A high ratio of the CD3
      CD56+ NK subset was associated with poorer overall survival in lung and
      colorectal cancer, but not HCC. In conclusion, the CD3+CD8+ and CD3+CD56+
      subsets, especially the CD3+CD8+ subset, may be the major phenotypes responsible
      for anti-tumor immunity in vivo after autogenous CIK cell therapy. 

PMID- 23955803
TI  - Land-sharing versus land-sparing logging: reconciling timber extraction with
      biodiversity conservation.
AB  - Selective logging is a major driver of rainforest degradation across the tropics.
      Two competing logging strategies are proposed to meet timber demands with the
      least impact on biodiversity: land sharing, which combines timber extraction with
      biodiversity protection across the concession; and land sparing, in which higher
      intensity logging is combined with the protection of intact primary forest
      reserves. We evaluate these strategies by comparing the abundances and species
      richness of birds, dung beetles and ants in Borneo, using a protocol that allows
      us to control for both timber yield and net profit across strategies. Within each
      taxonomic group, more species had higher abundances with land-sparing than land
      sharing logging, and this translated into significantly higher species richness
      within land-sparing concessions. Our results are similar when focusing only on
      species found in primary forest and restricted in range to Sundaland, and they
      are independent of the scale of sampling. For each taxonomic group, land-sparing
      logging was the most promising strategy for maximizing the biological value of
      logging operations. 

PMID- 23955806
TI  - High-sensitivity troponin assays and the early rule-out of acute myocardial
      infarction.

PMID- 23955804
TI  - A high-throughput screen for antibiotic drug discovery.
AB  - We describe an ultra-high-throughput screening platform enabling discovery and/or
      engineering of natural product antibiotics. The methodology involves creation of
      hydrogel-in-oil emulsions in which recombinant microorganisms are co-emulsified
      with bacterial pathogens; antibiotic activity is assayed by use of a fluorescent
      viability dye. We have successfully utilized both bulk emulsification and
      microfluidic technology for the generation of hydrogel microdroplets that are
      size-compatible with conventional flow cytometry. Hydrogel droplets are ~25 pL in
      volume, and can be synthesized and sorted at rates exceeding 3,000 drops/s. Using
      this technique, we have achieved screening throughputs exceeding 5 million
      clones/day. Proof-of-concept experiments demonstrate efficient selection of
      antibiotic-secreting yeast from a vast excess of negative controls. In addition,
      we have successfully used this technique to screen a metagenomic library for
      secreted antibiotics that kill the human pathogen Staphylococcus aureus. Our
      results establish the practical utility of the screening platform, and we
      anticipate that the accessible nature of our methods will enable others seeking
      to identify and engineer the next generation of antibacterial biomolecules.

PMID- 23955807
TI  - Soil properties affect the toxicities of 2,4,6-trinitrotoluene (TNT) and
      hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) to the enchytraeid worm Enchytraeus
      crypticus.
AB  - The authors investigated individual toxicities of 2,4,6-trinitrotoluene (TNT) and
      hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) to the potworm Enchytraeus
      crypticus using the enchytraeid reproduction test. Studies were designed to
      generate ecotoxicological benchmarks that can be used for developing ecological
      soil-screening levels for ecological risk assessments of contaminated soils and
      to identify and characterize the predominant soil physicochemical parameters that
      can affect the toxicities of TNT and RDX to E. crypticus. Soils, which had a wide
      range of physicochemical parameters, included Teller sandy loam, Sassafras sandy
      loam, Richfield clay loam, Kirkland clay loam, and Webster clay loam. Analyses of
      quantitative relationships between the toxicological benchmarks for TNT and soil
      property measurements identified soil organic matter content as the dominant
      property mitigating TNT toxicity for juvenile production by E. crypticus in
      freshly amended soil. Both the clay and organic matter contents of the soil
      modulated reproduction toxicity of TNT that was weathered and aged in soil for 3
      mo. Toxicity of RDX for E. crypticus was greater in the coarse-textured sandy
      loam soils compared with the fine-textured clay loam soils. The present studies
      revealed alterations in toxicity to E. crypticus after weathering and aging TNT
      in soil, and these alterations were soil- and endpoint-specific.

PMID- 23955808
TI  - XIAP Q423P polymorphism and susceptibility to childhood hemophagocytic
      lymphohistiocytosis.

PMID- 23955809
TI  - Patchy nanoparticles: Curvature makes a difference.

PMID- 23955810
TI  - Geometric curvature controls the chemical patchiness and self-assembly of
      nanoparticles.
AB  - When organic molecules are tethered onto non-spherical nanoparticles, their
      chemical properties depend on the particles' local curvature and shape. Based on
      this observation, we show here that it is possible to engineer chemical
      patchiness across the surface of a non-spherical nanoparticle using a single
      chemical species. In particular, when acidic ligands are used, regions of the
      particle surface with different curvature become charged at different pH values
      of the surrounding solution. This interplay between particle shape and local
      electrostatics allows for fine control over nanoscale self-assembly leading to
      structures with varying degrees of complexity. These structures range from
      particle cross-stacks to open-lattice crystals, the latter with pore sizes on the
      order of tens of nanometres, that is, at the lower synthetic limits of metallic
      mesoporous materials. 

PMID- 23955811
TI  - Flow-based solution-liquid-solid nanowire synthesis.
AB  - Discovered almost two decades ago, the solution-liquid-solid (SLS) method for
      semiconductor nanowire synthesis has proven to be an important route to high
      quality, single-crystalline anisotropic nanomaterials. In execution, the SLS
      technique is similar to colloidal quantum-dot synthesis in that it entails the
      injection of chemical precursors into a hot surfactant solution, but
      mechanistically it is considered the solution-phase analogue to vapour-liquid
      solid (VLS) growth. Both SLS and VLS methods make use of molten metal
      nanoparticles to catalyse the nucleation and elongation of single-crystalline
      nanowires. Significantly, however, the methods differ in how chemical precursors
      are introduced to the metal catalysts. In SLS, precursors are added in a one-off
      fashion in a flask, whereas in VLS they are carried by a flow of gas through the
      reaction chamber, and by-products are removed similarly. The ability to
      dynamically control the introduction of reactants and removal of by-products in
      VLS synthesis has enabled a degree of synthetic control not possible with SLS
      growth. We show here that SLS synthesis can be transformed into a continuous
      technique using a microfluidic reactor. The resulting flow-based SLS ('flow-SLS')
      platform allows us to slow down the synthesis of nanowires and capture
      mechanistic details concerning their growth in the solution phase, as well as
      synthesize technologically relevant axially heterostructured semiconductor
      nanowires, while maintaining the propensity of SLS for accessing ultrasmall
      diameters below 10 nm. 

PMID- 23955813
TI  - Rationale use of GLP-1 receptor agonists in patients with type 1 diabetes.
AB  - Clinicians and patients are rapidly adapting GLP-1 receptor agonists as
      efficacious and safe therapeutic options for managing type 2 diabetes (T2DM). GLP
      1 receptor agonists stimulate insulin production and secretion from the
      pancreatic beta cells in a glucose-dependent manner, improve gastric emptying,
      favor weight reduction, and reduce postabsorptive glucagon secretion from
      pancreatic alpha cells. GLP-1 receptor activity is impaired in patients with
      T2DM. GLP-1 secretion and subsequent physiologic actions in patients with type 1
      diabetes (T1DM) is ill-defined. Some researchers have suggested that the use of
      GLP-1 receptor agonists in T1DM may reduce excessive postprandial glucagon
      secretion allowing patients to reduce their total daily dose of exogenous
      insulin. Hypoglycemia risk may also be minimized in T1DM as glucagon counter
      regulation can be preserved to some degree via the glucose-dependent action of
      the GLP-1 receptor agonists. This paper will consider the physiologic and
      pharmacologic benefits of adding GLP-1 receptor agonists to therapeutic regimens
      of patients with T1DM. 

PMID- 23955812
TI  - Functional polymorphisms of matrix metalloproteinase-9 and survival in patients
      with locoregionally advanced nasopharyngeal carcinoma treated with
      chemoradiotherapy.
AB  - To investigate the prognostic role of major matrix metalloproteinase (MMP) gene
      polymorphisms in patients with locoregionally advanced nasopharyngeal carcinoma
      (NPC) treated with chemoradiotherapy. Four hundred twenty-one consecutive NPC
      patients were prospectively recruited. Two hundred patients were randomly
      selected as the training cohort, and the remaining 221 patients were the
      validation cohort. Twelve polymorphisms in the MMP-1, 2, 3, 7, 8, and 9 genes
      were genotyped by ligase detection reaction-PCR. MMP-9 rs2250889 PR/RR (HR =
      2.287, 95% CI 1.400-3.735) and rs17576 RQ/QQ (HR = 2.347, 95% CI 1.431-3.849)
      genotypes were significantly related with increased death risk in the training
      cohort. Analysis of the validation cohort confirmed these results (rs2250889: HR
      = 2.231, 95% CI 1.281-3.886; rs17576: HR = 2.987, 95% CI 1.674-5.330).
      Multivariate analysis showed that rs17576 (HR = 2.284, 95% CI 1.123-4.643, P =
      0.023) was still an independent prognostic factor. The MMP-9 rs17576 is a novel
      independent prognostic marker in patients with locoregionally advanced NPC
      treated with chemoradiotherapy.

PMID- 23955814
TI  - Is Tetranychus urticae suitable prey for development and reproduction of naive
      Coleomegilla maculata?
AB  - The lady beetle Coleomegilla maculata De Geer is an omnivorous predator that
      could help suppress aphid and spider mite populations on plants in greenhouses,
      plantscapes or interiorscapes. We are assessing the nutritional requirements and
      feeding behavior of C. maculata on target prey (spider mites) and factitious
      (unnatural) food. Our ultimate goal is to develop an efficacious diet to mass
      produce C. maculata. In this study, we tested the hypothesis that Tetranychus
      urticae Koch (two-spotted spider mite) is not suitable prey for development and
      reproduction of naive C. maculata (i.e., with no prior exposure to T. urticae).
      Our objectives were to (i) provide baseline data on the effects of consuming T.
      urticae on C. maculata life history, (ii) to compare the effects of consuming all
      stages of T. urticae versus eggs of Musca domestica L. (common housefly), and
      (iii) to determine if the consumption of plant products was beneficial. We used
      C. maculata from a colony reared only on Ephestia kuehniella Zeller
      (Mediterranean flour moth) eggs. In experiments, C. maculata larvae were reared
      from the first instar to adult stage with prey/food in replicated arenas; adult
      females were paired with a single male with prey/food. The results showed that
      naive C. maculata readily attacked and consumed T. urticae. Nevertheless, T.
      urticae was less suitable than M. domestica eggs for C. maculata development and
      reproduction. Applying a synthetic pollen-Chlorella alga powder (SPCA) in arenas
      containing T. urticae appeared to boost C. maculata female development and
      reproduction. 

PMID- 23955816
TI  - Robotic cholecystectomy: training of residents in use of the robotic platform.
AB  - BACKGROUND: The expanding use of robotic technology has introduced a requirement
      to incorporate this technology into traditional training programs. The goal of
      this study is to demonstrate the safe introduction of the robotic surgical system
      during residency programs, using robotic cholecystectomy as the basic procedure.
      METHODS: A total of 170 patients who underwent robotic cholecystectomy at a
      tertiary center were retrospectively reviewed. Data collected included patient's
      age, gender, weight, BMI, operative time, hospital stay, associated procedures,
      and complications. RESULTS: Of the 170 patients, mean age, BMI, operative time
      and estimated blood loss was 40.04 years, 32.78 kg/m(2) , 93.79 minutes and 13.67
      mL, respectively, with acceptable complications. CONCLUSIONS: Within the context
      of a traditional residency program, a standardized training curriculum and
      technique can be applied to educate residents without increasing surgical
      complication in the use of robotic platform. Robotic cholecystectomy is a safe
      and appropriate basic procedure to provide this training.

PMID- 23955817
TI  - Influence of stem design on the primary stability of megaprostheses of the
      proximal femur.
AB  - PURPOSE: Extended bone defects of the proximal femur can be reconstructed by
      megaprostheses for which aseptic loosening constitutes one of the major failure
      modes. The basic requirement for long-term success of endoprostheses is primary
      stability. We therefore assessed whether sufficient primary stability can be
      achieved by four different megaprostheses in a standardised bone defect of the
      proximal femur and whether their different design leads to different fixation
      patterns. METHODS: Four different designs of proximal femoral replacements were
      implanted into 16 Sawbones(r) after preparing segmental bone defects (AAOS type
      II). Primary rotational stability was analysed by application of a cyclic torque
      of +/-7 Nm and measuring the relative micromotions between bone and implant at
      different levels. The main fixation zones and differences of fixation patterns of
      the stem designs were determined by an analysis of variance. RESULTS: All four
      implants exhibited micromotions below 150 MUm, indicating adequate primary
      stability. Lowest micromotions for all designs were located near the femoral
      isthmus. The extent of primary stability and the global implant fixation pattern
      differed considerably and could be related to the different design concepts.
      CONCLUSIONS: All megaprostheses studied provided sufficient primary stability if
      the fixation conditions of the femoral isthmus were intact. The design
      characteristics of the different stems largely determined the extent of primary
      stability and fixation pattern. Understanding these different fixation types
      could help the surgeon to choose the most suitable implant if the fixation
      conditions in the isthmus are compromised.

PMID- 23955818
TI  - Do changes in torsional magnetic resonance imaging reflect improvement in gait
      after femoral derotation osteotomy in patients with cerebral palsy?
AB  - PURPOSE: Femoral derotation osteotomy (FDO) is commonly used to correct internal
      rotation gait (IRG) in spastic diplegia. The purpose of this study was to
      investigate whether the extent of intraoperative derotation is reflected in
      changes in static (clinical ROM and anteversion angle measured on torsional MRI)
      and dynamic parameters (transverse plane kinematics in three-dimensional gait
      analysis) after FDO in children with spastic diplegia. METHODS: In a prospective
      study, 30 children with spastic diplegia and IRG were treated with FDO as part of
      a multilevel surgery and were examined pre- and postoperatively clinically, by
      three-dimensional gait analysis and by torsional MRI according to a standardised
      protocol. RESULTS: A correlation (r = 0.317, p = 0.015) between the extent of
      intraoperative derotation and mean hip rotation in stance as well as the
      anteversion angle measured on torsional MRI (r = 0.454, p < 0.001) was found.
      However, no significant correlation was observed between anteversion angle (tMRI)
      and mean hip rotation in stance, either before or after FDO. CONCLUSIONS:
      Significant improvements were found in IRG after FDO, confirming the results of
      previous studies. There was no correlation between the anteversion measured on
      MRI and the mean hip rotation in stance in 3D gait analysis before or after FDO.
      Thus, the data suggest that if the intraoperative extent of derotation is
      determined only by the anteversion angle, the result will not be better after
      FDO. It might only help to avoid retroversion and indicate the maximum amount of
      femoral derotation. In this study the extent of the intraoperative derotation was
      orientated at the preoperative midpoint of rotation. Based on the small, but
      significant correlation between the clinical midpoint and the mean hip rotation
      in stance in the gait analysis, determination of the intraoperative extent of
      derotation according to the mean hip rotation in stance seems to give the best
      results.

PMID- 23955819
TI  - Results of Mannerfelt wrist arthrodesis for rheumatoid arthritis in relation to
      the position of the fused wrist.
AB  - PURPOSE: The wrist is involved early in rheumatoid arthritis and is often
      severely affected. A stable wrist is crucial to good hand function, which often
      necessitates a fusion. One of the most commonly used techniques in rheumatoid
      patients is the Mannerfelt arthrodesis. In this retrospective study the outcome
      and the patient's subjective satisfaction are presented and compared to other
      techniques. Also the influence of the position of the wrist following a fusion
      procedure is analysed. METHODS: Thirty-four wrists were retrospectively analysed
      using radiological measurements, functional scores such as the Disabilities of
      the Arm, Shoulder and Hand (DASH) and a pain assessment. The objective function
      of the hand with the fused wrist was assessed. RESULTS: In 92.6% of wrists the
      patients rated their satisfaction as good or excellent. The mean DASH score post
      operatively was 63.3. Of the wrists, 17 were fixed in a median flexed position of
      13 degrees  and 17 wrists in a median extended position of 8 degrees . There was
      no statistically significant correlation between the position of the wrist and
      the satisfaction or objective function. The rate of fusion was 94.1%.
      CONCLUSIONS: The Mannerfelt arthrodesis achieves good results and provides a high
      rate of satisfaction and pain relief in our study. It has major advantages
      compared to other wrist fusion techniques in the rheumatoid patient. We could not
      show clear statistical evidence for better results in either a flexed or an
      extended position, but the ratings of the patients indicated better subjective
      results with a slightly extended position of the arthrodesis.

PMID- 23955820
TI  - RNA interference: a powerful tool in entomological research and a novel approach
      for insect pest management.

PMID- 23955821
TI  - Delivery of dsRNA for RNAi in insects: an overview and future directions.
AB  - RNA interference (RNAi) refers to the process of exogenous double-stranded RNA
      (dsRNA) silencing the complementary endogenous messenger RNA. RNAi has been
      widely used in entomological research for functional genomics in a variety of
      insects and its potential for RNAi-based pest control has been increasingly
      emphasized mainly because of its high specificity. This review focuses on the
      approaches of introducing dsRNA into insect cells or insect bodies to induce
      effective RNAi. The three most common delivery methods, namely, microinjection,
      ingestion, and soaking, are illustrated in details and their advantages and
      limitations are summarized for purpose of feasible RNAi research. In this review,
      we also briefly introduce the two possible dsRNA uptake machineries, other dsRNA
      delivery methods and the history of RNAi in entomology. Factors that influence
      the specificity and efficiency of RNAi such as transfection reagents, selection
      of dsRNA region, length, and stability of dsRNA in RNAi research are discussed
      for further studies.

PMID- 23955822
TI  - Feasibility, limitation and possible solutions of RNAi-based technology for
      insect pest control.
AB  - Numerous studies indicate that target gene silencing by RNA interference (RNAi)
      could lead to insect death. This phenomenon has been considered as a potential
      strategy for insect pest control, and it is termed RNAi-mediated crop protection.
      However, there are many limitations using RNAi-based technology for pest control,
      with the effectiveness target gene selection and reliable double-strand RNA
      (dsRNA) delivery being two of the major challenges. With respect to target gene
      selection, at present, the use of homologous genes and genome-scale high
      throughput screening are the main strategies adopted by researchers. Once the
      target gene is identified, dsRNA can be delivered by micro-injection or by
      feeding as a dietary component. However, micro-injection, which is the most
      common method, can only be used in laboratory experiments. Expression of dsRNAs
      directed against insect genes in transgenic plants and spraying dsRNA reagents
      have been shown to induce RNAi effects on target insects. Hence, RNAi-mediated
      crop protection has been considered as a potential new-generation technology for
      pest control, or as a complementary method of existing pest control strategies;
      however, further development to improve the efficacy of protection and range of
      species affected is necessary. In this review, we have summarized current
      research on RNAi-based technology for pest insect management. Current progress
      has proven that RNAi technology has the potential to be a tool for designing a
      new generation of insect control measures. To accelerate its practical
      application in crop protection, further study on dsRNA uptake mechanisms based on
      the knowledge of insect physiology and biochemistry is needed.

PMID- 23955823
TI  - Advances in the use of the RNA interference technique in Hemiptera.
AB  - RNA interference (RNAi) suppresses the expression of target genes by post
      transcriptional regulation. Because double-stranded RNA (dsRNA) mediated gene
      silencing is a conserved mechanism in many eukaryotes, RNAi has become a valuable
      tool for unveiling gene function in many model insects. Recent research has also
      shown that RNAi can also be effective in the downregulation of target genes in
      Hemiptera. In this review, we discuss the use of the RNAi technique in gene
      functional analysis in hemipterans, highlighting the methods of dsRNA uptake by
      these insects and discuss the knock-down efficiency of these techniques. Although
      the RNAi technique has disadvantages, our primary goal here is to determine
      whether it can be exploited further in the discovery of new gene functions, and
      as a pest control strategy, in some important Hemipteran pests.

PMID- 23955824
TI  - Application of RNA interference in triatomine (Hemiptera: Reduviidae) studies.
AB  - Triatomines (Hemiptera: Reduviidae) are obligate hematophagous insects. They are
      of medical importance because they are vectors of Trypanosoma cruzi, the
      causative agent of Chagas disease in the Americas. In recent years, the RNA
      interference (RNAi) technology has emerged as a practical and useful alternative
      means of studying gene function in insects, including triatomine bugs. RNAi
      research in triatomines is still in its early stages, several issues still need
      to be elucidated, including the description of the molecules involved in the RNAi
      machinery and aspects related to phenotype evaluation and persistence of the
      knockdown in different tissues and organs. This review considers recent
      applications of RNAi to triatomine research, describing the major methods that
      have been applied during the knockdown process such as the double-stranded RNA
      delivery mechanism (injection, microinjection, or ingestion) and the phenotype
      characterization (mRNA and target protein levels) in studies conducted with the
      intent to provide greater insights into the biology of these insects. In addition
      to the characterization of insect biomolecules, some with biopharmacological
      potential, RNAi may provide a new view of the interaction between triatomine and
      trypanosomatids, enabling the development of new measures for vector control and
      transmission of the parasite.

PMID- 23955825
TI  - MicroRNA-dependent development revealed by RNA interference-mediated gene
      silencing of LmDicer1 in the migratory locust.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs, which participate in many biological
      processes. The small RNA transcriptome in the migratory locust has been
      characterized and 50 conserved miRNA families and 185 potential locust-specific
      miRNA family candidates have been identified using high-throughput sequencing.
      However, it is unclear whether miRNAs influence a wide variety of locusts'
      biological processes, such as growth or development. In insects, Dicer1
      ribonuclease transforms miRNA precursors into mature miRNAs. Thus, using systemic
      RNA interference (RNAi) to silence the expression of Dicer1 in the migratory
      locust, Locusta migratoria, we reduced miRNA contents in the locust and disrupted
      two types of molt (nymph-nymph, and nymph-adult). The RNAi of LmDicer1 also
      resulted in a high mortality in L. migratora. Our study revealed that LmDicer1
      was essential for miRNA regulation and development of L. migratoria. These
      results further support our notion that LmDicer1 could serve as an excellent
      target for developing novel strategies for controlling this important insect
      pest.

PMID- 23955826
TI  - Molecular characterization and gene functional analysis of Dicer-2 gene from
      Nilaparvata lugens (Hemiptera: Geometroidea).
AB  - Nilaparvata lugens (Stal) (Hemiptera: Geometroidea), a serious rice pest in many
      countries of Asia, causes a great loss in rice production every year. RNA
      interference (RNAi) is a powerful technology for gene function study in insects
      and a potential tool for pest control. As a core component of RNAi pathway, Dicer
      2 (Dcr-2) protein determines the production of small interfering RNA (siRNA) and
      is crucial for the efficiency of RNAi. In this study, the full-length
      complementary DNA (cDNA) of N. lugens Dcr-2 (NlDcr-2) was first cloned and
      analyzed, and then the RNAi experiment was conducted to explore the function of
      NlDcr-2 gene. The complete Dcr-2 cDNA of N. lugens was 4 971 bp in length with an
      open reading frame (ORF) of 1,656 amino acids. Phylogenetic and protein domain
      analysis showed that the predicted NlDcr-2 protein was similar to Tribolium
      castaneum. In the RNAi experiment, the messenger RNA level of NlDcr-2 was
      significantly reduced by NlDcr-2 double-stranded RNA (dsRNA) (dsDcr-2). Fifty
      five per cent decrease of NlDcr-2 was found after 4 days of unremitting feeding.
      No significant effect was observed on the development of N. lugens after dsRNA
      ingestion.

PMID- 23955827
TI  - Coexpression of Escherichia coli RNase III in silkworm cells improves the
      efficiency of RNA interference induced by long hairpin dsRNAs.
AB  - Long hairpin dsRNA transcribed from chromosomal DNA can induce RNA interference
      in Bombyx mori cells, although its gene silencing efficiency is lower than that
      of exogenously introduced double-stranded RNAs (dsRNAs). To solve this problem,
      we monitored the nuclear cytoplasmic translocation of the transcribed hairpin
      dsRNA and analyzed the processing efficiency into mature small interfering RNA
      (siRNA). Northern blot analysis revealed that the transcribed hairpin dsRNAs were
      spliced and transported into the cytoplasm, but were not effectively diced into
      siRNAs. Interestingly, RNAi with hairpin dsRNAs from genome-integrated IR
      transgene was stimulated by the coexpression of Escherichia coli RNase III,
      although this exogenous enzyme seemed to bring about nonspecific cleavage of
      cellular mRNA.

PMID- 23955828
TI  - Characterization of Argonaute family members in the silkworm, Bombyx mori.
AB  - The Argonaute protein family is a highly conserved group of proteins, which have
      been implicated in RNA silencing in both plants and animals. Here, four members
      of the Argonaute family were systemically identified based on the genome sequence
      of Bombyx mori. Based on their sequence similarity, BmAgo1 and BmAgo2 belong to
      the Ago subfamily, while BmAgo3 and BmPiwi are in the Piwi subfamily.
      Phylogenetic analysis reveals that silkworm Argonaute family members are
      conserved in insects. Conserved amino acid residues involved in recognition of
      the 5' end of the small RNA guide strand and of the conserved (aspartate,
      aspartate and histidine [DDH]) motif present in their PIWI domains suggest that
      these four Argonaute family members may have conserved slicer activities. The
      results of microarray expression analysis show that there is a low expression
      level for B. mori Argonaute family members in different tissues and different
      developmental stages, except for BmPiwi. All four B. mori Argonaute family
      members are upregulated upon infection with B. mori nucleopolyhedrovirus. The
      complete coding sequence of BmPiwi, the homolog of Drosophila piwi, was cloned
      and its expression occurred mainly in the area where spermatogonia and
      spermatocytes appear. Our results provide an overview of the B. mori Argonaute
      family members and suggest that they may have multiple roles. In addition, this
      is also the first report, to our knowledge, of the response of RNA silencing
      machinery to DNA virus infection in insects.

PMID- 23955829
TI  - In vitro and in vivo application of RNA interference for targeting genes involved
      in peritrophic matrix synthesis in a lepidopteran system.
AB  - The midgut of most insects is lined with a semipermeable acellular tube, the
      peritrophic matrix (PM), composed of chitin and proteins. Although various genes
      encoding PM proteins have been characterized, our understanding of their roles in
      PM structure and function is very limited. One promising approach for obtaining
      functional information is RNA interference, which has been used to reduce the
      levels of specific mRNAs using double-stranded RNAs administered to larvae by
      either injection or feeding. Although this method is well documented in dipterans
      and coleopterans, reports of its success in lepidopterans are varied. In the
      current study, the silencing midgut genes encoding PM proteins (insect intestinal
      mucin 1, insect intestinal mucin 4, PM protein 1) and the chitin biosynthetic or
      modifying enzymes (chitin synthase-B and chitin deacetylase 1) in a noctuid
      lepidopteran, Mamestra configurata, was examined in vitro and in vivo. In vitro
      studies in primary midgut epithelial cell preparations revealed an acute and
      rapid silencing (by 24 h) for the gene encoding chitin deacetylase 1 and a slower
      rate of silencing (by 72 h) for the gene encoding PM protein 1. Genes encoding
      insect intestinal mucins were slightly silenced by 72 h, whereas no silencing was
      detected for the gene encoding chitin synthase-B. In vivo experiments focused on
      chitin deacetylase 1, as the gene was silenced to the greatest extent in vitro.
      Continuous feeding of neonates and fourth instar larvae with double-stranded RNA
      resulted in silencing of chitin deacetylase 1 by 24 and 36 h, respectively.
      Feeding a single dose to neonates also resulted in silencing by 24 h. The current
      study demonstrates that genes encoding PM proteins can be silenced and outlines
      conditions for RNA interference by per os feeding in lepidopterans.

PMID- 23955830
TI  - Limitations of RNAi of alpha6 nicotinic acetylcholine receptor subunits for
      assessing the in vivo sensitivity to spinosad.
AB  - Spinosad is a widely used insecticide that exerts its toxic effect primarily
      through interactions with the nicotinic acetylcholine receptor. The alpha6
      nicotinic acetylcholine receptor subunit is involved in spinosad toxicity as
      demonstrated by the high levels of resistance observed in strains lacking alpha6.
      RNAi was performed against the Dalpha6 nicotinic acetylcholine receptor subunit
      in Drosophila melanogaster using the Gal4-UAS system to examine if RNAi would
      yield results similar to those of Dalpha6 null mutants. These Dalpha6-deficient
      flies were subject to spinosad contact bioassays to evaluate the role of the
      Dalpha6 nicotinic acetylcholine receptor subunit on spinosad sensitivity. The
      expression of Dalpha6 was reduced 60%-75% as verified by quantitative polymerase
      chain reaction. However, there was no change in spinosad sensitivity in D.
      melanogaster. We repeated RNAi experiments in Tribolium castaneum using injection
      of dsRNA for Tcasalpha6. RNAi of Tcasalpha6 did not result in changes in spinosad
      sensitivity, similar to results obtained with D. melanogaster. The lack of change
      in spinosad sensitivity in both D. melanogaster and T. castaneum using two routes
      of dsRNA administration shows that RNAi may not provide adequate conditions to
      study the role of nicotinic acetylcholine receptor subunits on insecticide
      sensitivity due to the inability to completely eliminate expression of the alpha6
      subunit in both species. Potential causes for the lack of change in spinosad
      sensitivity are discussed.

PMID- 23955831
TI  - RNA interference to reveal roles of beta-N-acetylglucosaminidase gene during
      molting process in Locusta migratoria.
AB  - beta-N-acetylglucosaminidases are crucial enzymes involved in chitin degradation
      in insects. We identified a beta-N-acetylglucosaminidase gene (LmNAG1) from
      Locusta migratoria. The full-length complementary DNA (cDNA) of LmNAG1 consists
      of 2 667 nucleotides, including an open reading frame (ORF) of 1 845 nucleotides
      encoding 614 amino acid residues, and 233- and 589-nucleotide non-coding regions
      at the 5'- and 3'-ends, respectively. Phylogenetic analysis grouped the cDNA
      deduced LmNAG1 protein with the enzymatically characterized beta-N
      acetylglucosaminidases in group I. Analyses of stage- and tissue-dependent
      expression patterns of LmNAG1 were carried out by real-time quantitative
      polymerase chain reaction. Our results showed that LmNAG1 transcript level in the
      integument was significantly high in the last 2 days of the fourth and fifth
      instar nymphs. LmNAG1 was highly expressed in foregut and hindgut. RNA
      interference of LmNAG1 resulted in an effective silence of the gene and a
      significantly reduced total LmNAG enzyme activity at 48 and 72 h after the
      injection of LmNAG1 double-stranded RNA (dsRNA). As compared with the control
      nymphs injected with GFP dsRNA, 50% of the dsLmNAG1-injected nymphs were not able
      to molt successfully and eventually died. Our results suggest that LmNAG1 plays
      an essential role in molting process of L. migratoria.

PMID- 23955832
TI  - A commentary on 'Defining substance use disorders: do we really need more than
      heavy use?'.
AB  - Defining substance use disorders as heavy use will help to reduce fruitless
      discussions about labeling, reduce stigma and increase the likelihood of people
      coming forward for help of whatever level of intensity best matches their needs.
      Clinicians will still need to assess propensity for withdrawal symptoms and help
      the heaviest drinkers to work out whether they can successfully maintain a
      reduced consumption level rather than abstinence.

PMID- 23955833
TI  - Neuropsychological rehabilitation in alcohol-related brain damage: a systematic
      review.
AB  - AIMS: The evidence base for rehabilitating alcohol-related brain damage (ARBD) is
      still in its infancy. The aim of this review was to collate evidence of
      intervention studies for ARBD and Wernicke-Korsakoff syndrome (WKS), to offer
      some indication of methodological quality, and to suggest directions for future
      research in this area. METHODS: A comprehensive search strategy resulted in
      systematic review of 16 studies investigating neurorehabilitation of cognitive
      impairment relating to ARBD. RESULTS: Most studies addressed rehabilitation of
      the memory impairments associated with Korsakoff's syndrome, although one study
      seeking to remediate executive functioning impairment was also included. Three
      studies outlining service models or approaches were included, with the aim of
      generating advances in service development for this population. CONCLUSION: The
      reviewed studies were of varying methodology, allowing only tentative
      conclusions. However, the available evidence suggested benefits of a number of
      memory rehabilitation strategies. Options for practice are suggested.

PMID- 23955834
TI  - Why not add consumption measures to current definitions of substance use
      disorders? Commentary on Rehm et al.: 'Defining substance use disorders: do we
      really need more than heavy use?'.
AB  - The article by Rehm and colleagues in this issue of the Journal argues that
      diagnoses of substance use disorders should be based solely on measures of
      consumption. Although the authors provide convincing arguments for inclusion of
      consumption measures in the diagnostic criteria for substance use disorders, we
      do not agree that diagnostic criteria should be restricted to measures of
      consumption alone. Our clinical and research experience with alcohol use
      disorders suggests that use of consumption measures alone would fail to identify
      many patients whose alcohol or drug use is adversely impacting their health.
      Instead, we advocate-as others have done-that measures of consumption be added to
      current diagnostic criteria. 

PMID- 23955835
TI  - Rapid onset of perfused blood vessels after implantation of ECFCs and MPCs in
      collagen, PuraMatrix and fibrin provisional matrices.
AB  - We developed an in vivo vascularization model in which human endothelial colony
      forming cells (ECFCs) and human mesenchymal progenitor cells (MPCs) form blood
      vessel networks when co-injected (ECFC + MPC) into nude mice in rat tail type I
      collagen, bovine fibrin or synthetic peptide PuraMatrix matrices. We used three
      approaches to determine the onset of functional vascularization when ECFC + MPC
      suspended in these matrices were implanted in vivo. The first was
      immunohistochemistry to detect vessels lined by human endothelial cells and
      filled with red blood cells. The second was in vivo vascular staining by tail
      vein injection of a mixture of Ulex europaeus agglutinin I (UEA-I), a lectin
      specific for human endothelium, and Griffonia simplicifolia isolectin B4 (GS-IB4
      ), a lectin specific for rodent endothelium. The third approach employed contrast
      enhanced ultrasound to measure the perfusion volumes of implants in individual
      animals over time. Human endothelial-lined tubular structures were detected in
      vivo on days 1 and 2 after implantation, with perfused human vessels detected on
      days 3 and 4. Contrast-enhanced ultrasound revealed significant perfusion of ECFC
      + MPC/collagen implants on days 1-4, at up to 14% perfused vascular volume. ECFC
      + MPC implanted in fibrin and PuraMatrix matrices also supported perfusion at day
      1, as assessed by ultrasound (at 12% and 23% perfused vascular volume,
      respectively). This model demonstrates that ECFC + MPC suspended in any of the
      three matrices initiated a rapid onset of vascularization. We propose that ECFC +
      MPC delivered in vivo provide a means to achieve rapid perfusion of tissue
      engineered organs or for in situ tissue repair.

PMID- 23955836
TI  - PCy3-catalyzed ring expansion of aziridinofullerenes with CO2 and aryl
      isocyanates: evidence for a two consecutive nucleophilic substitution pathway on
      the fullerene cage.
AB  - A PCy3-catalyzed ring-expansion reaction of aziridine-fused fullerenes
      (aziridinofullerenes) through the insertion of CO2 and aryl isocyanates is
      disclosed. The reaction allows for CO2 fixation by aziridinofullerenes, producing
      oxazolidinone-fused fullerenes (oxazolidinofullerenes) in high yields, whereas
      treatment with aryl isocyanates led to a new fullerene family-imidazolidinone
      fused fullerenes (imidazolidinofullerenes)-in good to high yields. Furthermore, a
      mechanistically related unprecedented fullerenyl phosphonium salt was
      successfully isolated. Using the isolated salt, mechanistic studies were also
      investigated.

PMID- 23955837
TI  - Choosing wisely in pediatric hospital medicine: five opportunities for improved
      healthcare value.
AB  - BACKGROUND: Despite estimates that waste constitutes up to 20% of healthcare
      expenditures in the United States, overuse of tests and therapies is
      significantly under-recognized in medicine, particularly in pediatrics. The
      American Board of Internal Medicine Foundation developed the Choosing Wisely
      campaign, which challenged medical societies to develop a list of 5 things
      physicians and patients should question. The Society of Hospital Medicine (SHM)
      joined this effort in the spring of 2012. This report provides the pediatric work
      group's results. METHODS: A work group of experienced and geographically
      dispersed pediatric hospitalists was convened by the Quality and Safety Committee
      of the SHM. This group developed an initial list of 20 recommendations, which was
      pared down through a modified Delphi process to the final 5 listed below.
      RESULTS: The top 5 recommendations proposed for pediatric hospital medicine are:
      (1) Do not order chest radiographs in children with asthma or bronchiolitis. (2)
      Do not use systemic corticosteroids in children under 2 years of age with a lower
      respiratory tract infection. (3) Do not use bronchodilators in children with
      bronchiolitis. (4) Do not treat gastroesophageal reflux in infants routinely with
      acid suppression therapy. (5) Do not use continuous pulse oximetry routinely in
      children with acute respiratory illness unless they are on supplemental oxygen.
      CONCLUSION: We recommend that pediatric hospitalists use this list to prioritize
      quality improvement efforts and include issues of waste and overuse in their
      efforts to improve patient care.

PMID- 23955838
TI  - Enzymatic hydrolysis of pelletized AFEXTM-treated corn stover at high solid
      loadings.
AB  - Ammonia fiber expansion (AFEXTM) pretreatment can be performed at small depots,
      and the pretreated biomass can then be pelletized and shipped to a centralized
      refinery. To determine the feasibility of this approach, pelletized AFEX-treated
      corn stover was hydrolyzed at high (18-36%) solid loadings. Water absorption and
      retention by the pellets was low compared to unpelletized stover, which allowed
      enzymatic hydrolysis slurries to remain well mixed without the need for fed-batch
      addition. Glucose yields of 68% and xylose yields of 65% were obtained with 20 mg
      enzyme/g glucan and 18% solid loading after 72 h, compared to 61% and 59% for
      unpelletized corn stover. Pelletization also slightly increased the initial rate
      of hydrolysis compared to unpelletized biomass. The ease of mixing and high
      yields obtained suggests that pelletization after AFEX pretreatment could have
      additional advantages beyond improved logistical handling of biomass.

PMID- 23955840
TI  - Editorial.

PMID- 23955839
TI  - Predictors of serum chlorinated pesticide concentrations among prepubertal
      Russian boys.
AB  - BACKGROUND: Few studies have evaluated predictors of childhood exposure to
      organochlorine pesticides (OCPs), a class of lipophilic persistent chemicals.
      OBJECTIVES: Our goal was to identify predictors of serum OCP concentrations
      hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p
      dichlorodiphenyldichloroethylene (p,p'-DDE)-among boys in Chapaevsk, Russia.
      METHODS: Between 2003 and 2005, 499 boys 8-9 years of age were recruited in a
      prospective cohort. The initial study visit included a physical examination;
      blood collection; health, lifestyle, and food-frequency questionnaires; and
      determination of residential distance from a local factory complex that produced
      HCB and beta-HCH. Fasting serum samples were analyzed for OCPs at the U.S.
      Centers for Disease Control and Prevention. General linear regression models were
      used to identify predictors of the boys' serum HCB, beta-HCH, and p,p'-DDE
      concentrations. RESULTS: Among 355 boys with OCP measurements, median serum HCB,
      beta-HCH, and p,p'-DDE concentrations were 158, 167, and 284 ng/g lipid,
      respectively. Lower body mass index, longer breastfeeding duration, and local
      dairy consumption were associated with higher concentrations of OCPs. Boys who
      lived < 2 km from the factory complex had 64% (95% CI: 37, 96) and 57% (95% CI:
      32, 87) higher mean HCB and beta-HCH concentrations, respectively, than boys who
      lived >= 5 km away. Living > 3 years in Chapaevsk predicted higher beta-HCH
      concentrations, and having parents who lacked a high school education predicted
      higher p,p'-DDE concentrations. CONCLUSIONS: Among this cohort of prepubertal
      Russian boys, predictors of serum OCPs included consumption of local dairy
      products, longer local residence, and residential proximity to the local factory
      complex.

PMID- 23955841
TI  - Biological and biochemical characterization of a red-eye mutant in Nilaparvata
      lugens (Hemiptera: Delphacidae).
AB  - A red-eye colony was established in our laboratory in brown planthopper (BPH),
      Nilaparvata lugens (Stal), a major rice pest in Asia. Except for the red-eye
      phenotype, no other differences were observed between the wild-type (brown eye)
      and the mutant-type (red eye) in external characters. Genetic analysis revealed
      that the red-eye phenotype was controlled by a single autosomal recessive allele.
      Biological studies found that egg production and egg viability in the red-eye
      mutant colony were not significantly different from those in the wild-type BPH.
      Biochemical analysis and electronic microscopy examination revealed that the red
      eye mutants contained decreased levels of both xanthommatin (brown) and pteridine
      (red) and reduced number of pigment granules. Thus, the changes of amount and
      ratio of the two pigments is the biochemical basis of this red-eye mutation. Our
      results indicate that the red-eye mutant gene (red) might be involved in one
      common gene locus shared by the two pigments in pigment transportation, pigment
      granule formation or some other processes. 

PMID- 23955842
TI  - Chronic illness in the workplace: stigma, identity threat and strain.
AB  - Chronic illness affects a large and growing number of workers in the United
      States and globally. Stigmatization (devaluation) at work based on chronic
      illness may be stressful for individuals and therefore may lead to negative
      psychological consequences (i.e. strains). In order to better understand
      stressful experiences of stigma for workers with chronic illnesses, a model of
      stigma-related identity threat (perceptions that one is at risk of being treated
      negatively at work because of chronic illness) was tested on a sample of 203
      working adults with chronic illnesses. The following variables related to
      workers' perceptions of chronic illness-related identity threat: workers'
      boundary flexibility (flexibility in managing their work and life), their meta
      perceptions of devaluation (perceptions of others' devaluation of them based on
      illness) and their job self-efficacy (feelings of confidence related to
      performing their job). In turn, perceptions of identity threat related to both
      feelings of psychological strain and (lower levels of) perceived work ability.
      Surprisingly, neither stigma centrality (how fundamental illness is to one's
      identity) nor supervisor support related to workers' identity threat perceptions.

PMID- 23955843
TI  - Justification for chest physiotherapy during ultra-protective lung ventilation
      and extra-corporeal membrane oxygenation: a case study.
AB  - BACKGROUND AND PURPOSE: This case report describes the chest physiotherapy (CPT)
      intervention provided to a 32-year old man with severe respiratory failure
      undergoing extra-corporeal membrane oxygenation (ECMO) support and ultra
      protective ventilatory strategy. Low tidal volume ventilation when used in
      patients with extremely low dynamic respiratory compliance may predispose the
      patient to secretion retention, and the role of CPT in this setting is unclear.
      METHOD: The method used is a single subject case report. Written consent obtained
      from patient's representative. SUMMARY: Secretion clearance in this patient was
      initially limited to suctioning; however, after developing major airway occlusion
      secondary to impacted secretions, he received intensive CPT consisting of
      positioning, ventilator hyperinflation, expiratory chest wall shaking and
      suctioning. After 13 days of two to three times daily CPT, the patient weaned
      from ECMO support. DISCUSSION: Regular CPT may have facilitated secretion
      clearance and lung recovery in this patient. Future research should investigate
      the optimal CPT techniques for patients with sub-dead space tidal ventilation and
      extremely low dynamic respiratory compliance during ECMO with ultra-protective
      ventilatory strategy (UPVS).

PMID- 23955844
TI  - A large-scale gene discovery for the red palm weevil Rhynchophorus ferrugineus
      (Coleoptera: Curculionidae).
AB  - The red palm weevil (RPW; Rhynchophorus ferrugineus) is a devastating pest of
      palms, prevalent in the Middle East as well as many other regions of the world.
      Here, we report a large-scale de novo complementary DNA (cDNA) sequencing effort
      that acquired ~5 million reads and assembled them into 26 765 contigs from 12
      libraries made from samples of different RPW developmental stages based on the
      Roche/454 GS FLX platform. We annotated these contigs based on the publically
      available known insect genes and the Tribolium castaneum genome assembly. We find
      that over 80% of coding sequences (CDS) from the RPW contigs have high-identity
      homologs to known proteins with complete CDS. Gene expression analysis shows that
      the pupa and larval stages have the highest and lowest expression levels,
      respectively. In addition, we also identified more than 60 000 single nucleotide
      polymorphisms and 1 200 simple sequence repeat markers. This study provides the
      first large-scale cDNA dataset for RPW, a much-needed resource for future
      molecular studies. 

PMID- 23955846
TI  - Three-dimensional morphometric comparison of normal and apoptotic endothelial
      cells based on laser scanning confocal microscopy observation.
AB  - Three-dimensional (3D) morphometric analysis of cellular and subcellular
      structures provides an effective method for spatial cell biology. Here, 3D
      cellular and nuclear morphologies are reconstructed to quantify and compare
      morphometric differences between normal and apoptotic endothelial cells. Human
      umbilical vein endothelial cells (HUVECs) are treated with 60 MUM H2 O2 to get
      apoptotic cell model and then a series of sectional images are acquired from
      laser scanning confocal microscopy. The 3D cell model containing plasma membrane
      and cell nucleus is reconstructed and fused utilizing three sequential softwares
      or packages (Mimics, Geomagic, and VTK). The results reveal that H2 O2 can induce
      apoptosis effectively by regulating the activity of apoptosis-related
      biomolecules, including pro-apoptotic factors p53 and Bax, and anti-apoptotic
      factor Bcl-2. Compared with the normal HUVECs, the apoptotic cells exhibit
      significant 3D morphometric parameters (height, volume and nucleus-to-cytoplasm
      ratio) variation. The present research provides a new perspective on comparative
      quantitative analysis associated with cell apoptosis and points to the value of
      LSCM as an objective tool for 3D cell reconstruction.

PMID- 23955845
TI  - Cholic acid modified 2 kDa polyethylenimine as efficient transfection agent.
AB  - New lipopolymers were synthesized by conjugating cholic acid (ChA) to
      polyethylenimines (PEI; 2 and 25 kDa) and a polyallylamine (PAA; 15 kDa) via N
      acylation to develop effective gene delivery systems. The extent of ChA
      substitution linearly varied with the feed ratio during synthesis, indicating
      good control over grafting ratio. While ChA did not affect binding to plasmid DNA
      (pDNA) for higher molecular weight (MW) polymers, ChA substitution to 2 kDa PEI
      significantly affected the pDNA binding. Toxicity of the 2 kDa PEI was unaffected
      by ChA substitution, but it was improved for the higher MW polymers. Using
      immortal 293T cells and primary cord blood-derived mesenchymal stem cells, low MW
      (2 kDa) PEI was shown to display much better transfection efficiency as a result
      of ChA substitution, unlike the higher MW polymers. We conclude that ChA could be
      a suitable substituent for non-toxic (low MW) PEIs in order to improve their
      transfection efficiency.

PMID- 23955847
TI  - Aggregation and mating success of Capnodis tenebrionis (Coleoptera: Buprestidae).
AB  - An understanding of the relative importance of extrinsic and intrinsic factors in
      determining the potential distribution and mating success of individuals is
      critical for the successful monitoring and management of pest species. Using a
      combination of field observations and a caged field experiment, we explored the
      roles of environmental and individual variation on the formation of mating
      aggregations and mating success in the buprestid beetle Capnodis tenebrionis
      (Linnaeus, 1767), a pest species of stone fruit trees. Our field observations
      revealed that the formation of aggregations is influenced by a range of
      environmental factors including temperature, photoperiod, and population density.
      However, aggregations were not at random and were more likely to occur on the
      section of the plant with highest incidence of solar radiation and thus higher
      temperatures. Data from our experiment with caged beetles in the field further
      indicate that the reproductive behavior of this species varies with temperature.
      The probability of a successful mating occurring was also positively related to
      both male and female size. Females of C. tenebrionis mate several times over a 4
      h period, but generally not with the same male. Information obtained from these
      studies is useful to define the most appropriate time for pest control,
      especially adopting strategies that interfere with reproduction.

PMID- 23955848
TI  - Coordinated control of bone cutting for a CT-free navigation robotic system in
      total knee arthroplasty.
AB  - BACKGROUND: Robots are gradually becoming intelligent tools for surgeons in
      computer assisted orthopedic surgery. A hands-on robot combining CT-free
      navigation software and coordinated control has been designed for total knee
      arthroplasty. METHODS: The hands-on robot is under bilateral force control so
      that the robot not only follows the force commands from the operator but also
      shapes the reflected force back to the operator. The proposed coordinated control
      also defines three operating modes to fulfill intelligent bone cutting by tuning
      appropriate scaling to the admittance gains. RESULTS: Experimental results
      demonstrated assistive, resistant and emergent actions to meet various bone
      cutting conditions by the coordinated controller. CONCLUSIONS: The proposed
      coordinated controller enables the robot to perform bone cutting more safely,
      rapidly and accurately compared with being performed by manual bone saw. The
      intelligent bone cutting has been successfully verified by a cadaver test.

PMID- 23955849
TI  - Invited reply to amikacin ototoxicity in children with cancer: the problem is the
      administration schedule.

PMID- 23955850
TI  - Regulation of lubricin/superficial zone protein by Wnt signalling in bovine
      synoviocytes.
AB  - Lubricin, homologous to superficial zone protein (SZP), functions as a boundary
      lubricant in articular cartilage and plays an essential role in the maintenance
      of joint function and homeostasis. Wnt signalling plays a key role in joint
      development, including synovial joint formation, and several Wnt proteins are
      expressed in the synovium and articular cartilage in arthritis. The aim of this
      study was to determine the role of Wnt signalling on SZP accumulation in
      synoviocytes. Isolated synoviocytes from bovine knee joints were cultured with
      Wnt proteins (Wnt-3a and Wnt-5a) and antagonists or agonists of the Wnt-beta
      catenin pathway or Wnt-Ca(2+) pathway in serum-free chemically defined medium.
      SZP accumulation in the culture medium was determined by enzyme-linked
      immunosorbent assay. Wnt-3a suppressed SZP accumulation via a Wnt-beta-catenin
      dependent pathway. In contrast, Wnt-5a stimulated SZP accumulation via a beta
      catenin independent pathway. The present investigation provides novel insights
      into the role of the Wnt signalling pathways in SZP accumulation in synoviocytes
      and their roles in the homeostasis of normal joints.

PMID- 23955851
TI  - Heteroleptic tin(II) initiators for the ring-opening (co)polymerization of
      lactide and trimethylene carbonate: mechanistic insights from experiments and
      computations.
AB  - The tin(II) complexes {LO(x)}Sn(X) ({LO(x)}(-) =aminophenolate ancillary)
      containing amido (1-4), chloro (5), or lactyl (6) coligands (X) promote the ring
      opening polymerization (ROP) of cyclic esters. Complex 6, which models the first
      insertion of L-lactide, initiates the living ROP of L-LA on its own, but the
      amido derivatives 1-4 require the addition of alcohol to do so. Upon addition of
      one to ten equivalents of iPrOH, precatalysts 1-4 promote the ROP of trimethylene
      carbonate (TMC); yet, hardly any activity is observed if tert-butyl (R)-lactate
      is used instead of iPrOH. Strong inhibition of the reactivity of TMC is also
      detected for the simultaneous copolymerization of L-LA and TMC, or for the block
      copolymerization of TMC after that of L-LA. Experimental and computational data
      for the {LO(x)}Sn(OR)complexes (OR=lactyl or lactidyl) replicating the active
      species during the tin(II)-mediated ROP of L-LA demonstrate that the formation of
      a five-membered chelate is largely favored over that of an eight-membered one,
      and that it constitutes the resting state of the catalyst during this
      (co)polymerization. Comprehensive DFT calculations show that, out of the four
      possible monomer insertion sequences during simultaneous copolymerization of L-LA
      and TMC: 1) TMC then TMC, 2) TMC then L-LA, 3) L-LA then L-LA, and 4) L-LA then
      TMC, the first three are possible. By contrast, insertion of L-LA followed by
      that of TMC (i.e., insertion sequence 4) is endothermic by +1.1 kcal mol(-1),
      which compares unfavorably with consecutive insertions of two L-LA units (i.e.,
      insertion sequence 3) (-10.2 kcal mol(-1)). The copolymerization of L-LA and TMC
      thus proceeds under thermodynamic control.

PMID- 23955852
TI  - Procalcitonin-guided antibiotic therapy: a systematic review and meta-analysis.
AB  - BACKGROUND: The utility of procalcitonin to manage patients with infections is
      unclear. A systematic review of comparative studies using procalcitonin-guided
      antibiotic therapy in patients with infections was performed. METHODS:
      Randomized, controlled trials comparing procalcitonin-guided initiation,
      intensification, or discontinuation of antibiotic therapy to clinically guided
      therapy were included. Outcomes were antibiotic usage, morbidity, and mortality.
      MEDLINE, EMBASE, the Cochrane Database, National Institute for Clinical
      Excellence, the National Guideline Clearinghouse, and the Health Technology
      Assessment Programme were searched from January 1, 1990 to December 16, 2011.
      RESULTS: Eighteen randomized, controlled trials were included. Data were pooled
      into clinically similar patient populations. In adult intensive care unit (ICU)
      patients, procalcitonin-guided discontinuation of antibiotics reduced antibiotic
      duration by 2.05 days (95% confidence interval [CI]: -2.59 to -1.52) without
      increasing morbidity or mortality. In contrast, procalcitonin-guided
      intensification of antibiotics in adult ICU patients increased antibiotic usage
      and morbidity. In adult patients with respiratory tract infections, procalcitonin
      guidance significantly reduced antibiotic duration by 2.35 days (95% CI: -4.38 to
      -0.33), antibiotic prescription rate by 22% (95% CI: -41% to -4%), and total
      antibiotic exposure without affecting morbidity or mortality. A single, good
      quality study of neonates with suspected sepsis demonstrated reduced antibiotic
      duration by 22.4 hours (P = 0.012) and reduced the proportion of neonates on
      antibiotics for >= 72 hours by 27% (P = 0.002) with procalcitonin guidance.
      CONCLUSION: Procalcitonin guidance can safely reduce antibiotic usage when used
      to discontinue antibiotic therapy in adult ICU patients and when used to initiate
      or discontinue antibiotics in adult patients with respiratory tract infections.

PMID- 23955853
TI  - Chitin synthesis inhibitors: old molecules and new developments.
AB  - Abstract  Chitin is the most abundant natural aminopolysaccharide and serves as a
      structural component of extracellular matrices. It is found in fungal septa,
      spores, and cell walls, and in arthropod cuticles and peritrophic matrices, squid
      pens, mollusk shells, nematode egg shells, and some protozoan cyst walls. As
      prokaryotes, plants and vertebrates including humans do not produce chitin, its
      synthesis is considered as an attractive target site for fungicides,
      insecticides, and acaricides. Although no chitin synthesis inhibitor has been
      developed into a therapeutic drug to treat fungal infections in humans, a larger
      number of compounds have been successfully launched worldwide to combat arthropod
      pests in agriculture and forestry. This review summarizes the latest advances on
      the mode of action of chitin synthesis inhibitors with a special focus on those
      molecules that act on a postcatalytic step of chitin synthesis. 

PMID- 23955854
TI  - The apical plasma membrane of chitin-synthesizing epithelia.
AB  - Abstract  Chitin is the second most abundant polysaccharide on earth. It is
      produced at the apical side of epidermal, tracheal, fore-, and hindgut epithelial
      cells in insects as a central component of the protective and supporting
      extracellular cuticle. Chitin is also an important constituent of the midgut
      peritrophic matrix that encases the food supporting its digestion and protects
      the epithelium against invasion by possibly ingested pathogens. The enzyme
      producing chitin is a glycosyltransferase that resides in the apical plasma
      membrane forming a pore to extrude the chains of chitin into the extracellular
      space. The apical plasma membrane is not only a platform for chitin synthases
      but, probably through its shape and equipment with distinct factors, also plays
      an important role in orienting and organizing chitin fibers. Here, I review
      findings on the cellular and molecular constitution of the apical plasma membrane
      of chitin-producing epithelia mainly focusing on work done in the fruit fly
      Drosophila melanogaster. 

PMID- 23955855
TI  - Cloning, expression and biocharacterization of OfCht5, the chitinase from the
      insect Ostrinia furnacalis.
AB  - Chitinase catalyzes beta-1,4-glycosidic linkages in chitin and has attracted
      research interest due to it being a potential pesticide target and an enzymatic
      tool for preparation of N-acetyl-beta-D-glucosamine. An individual insect
      contains multiple genes encoding chitinases, which vary in domain architectures,
      expression patterns, physiological roles and biochemical properties. Herein,
      OfCht5, the glycoside hydrolase family 18 chitinase from the widespread
      lepidopteran pest Ostrinia furnacalis, was cloned, expressed in the yeast Pichia
      pastoris and biochemically characterized in an attempt to facilitate both pest
      control and biomaterial preparation. Complementary DNA sequence analysis
      indicated that OfCHT5 consisted of an open reading frame of 1 665-bp nucleotides.
      Phylogenic analysis suggested OfCht5 belongs to the Group I insect chitinases.
      Expression of OfCht5 in Pichia pastoris resulted in highest specific activity
      after 120 h of induction with methanol. Through two steps of purification,
      consisting of ammonium sulfate precipitation and metal chelating chromatography,
      about 7 mg of the recombinant OfCht5 was purified to homogeneity from 1 L culture
      supernatant. OfCht5 effectively converted colloidal chitin into chitobiose, but
      had relatively low activity toward alpha-chitin. When chitooligosaccharides
      [(GlcNAc)n , n= 3-6] were used as substrates, OfCht5 was observed to possess the
      highest catalytic efficiency parameter toward (GlcNAc)4 and predominantely
      hydrolyzed the second glycosidic bond from the non-reducing end. Together with
      beta-N-acetyl-D-hexosaminidase OfHex1, OfCht5 achieved its highest efficiency in
      chitin degradation that yielded N-acetyl-beta-D-glucosamine, a valuable
      pharmacological reagent and food supplement, within a molar concentration ratio
      of OfCht5 versus OfHex1 in the range of 9 : 1-15 : 1. This work provides an
      alternative to existing preparation of chitinase for pesticides and other
      applications.

PMID- 23955856
TI  - Biochemical characterization of chitin synthase activity and inhibition in the
      African malaria mosquito, Anopheles gambiae.
AB  - Chitin synthase (CHS) is an important enzyme catalyzing the formation of chitin
      polymers in all chitin containing organisms and a potential target site for
      insect pest control. However, our understanding of biochemical properties of
      insect CHSs has been very limited. We here report enzymatic and inhibitory
      properties of CHS prepared from the African malaria mosquito, Anopheles gambiae.
      Our study, which represents the first time to use a nonradioactive method to
      assay CHS activity in an insect species, determined the optimal conditions for
      measuring the enzyme activity, including pH, temperature, and concentrations of
      the substrate uridine diphosphate N-acetyl-d-glucosamine (UDP-GlcNAc) and Mg(++)
      . The optimal pH was about 6.5-7.0, and the highest activity was detected at
      temperatures between 37 degrees C and 44 degrees C. Dithithreitol is required to
      prevent melanization of the enzyme extract. CHS activity was enhanced at low
      concentration of GlcNAc, but inhibited at high concentrations. Proteolytic
      activation of the activity is significant both in the 500 *g supernatant and the
      40 000 *g pellet. Our study revealed only slight in vitro inhibition of A.
      gambiae CHS activity by diflubenzuron and nikkomycin Z at the highest
      concentration (2.5 MUmol/L) examined. There was no in vitro inhibition by
      polyoxin D at any concentration examined. Furthermore, we did not observe any in
      vivo inhibition of CHS activity by any of these chemicals at any concentration
      examined. Our results suggest that the inhibition of chitin synthesis by these
      chemicals is not due to direct inhibition of CHS in A. gambiae.

PMID- 23955857
TI  - High-throughput genotyping of single-nucleotide polymorphisms in ace-1 gene of
      mosquitoes using MALDI-TOF mass spectrometry.
AB  - Acetylcholinesterase (AChE) plays a vital role in the nervous system of insects
      and other animal species and serves as the target for many chemical agents such
      as organophosphate and carbamate insecticides. The mosquito, Culex pipiens
      complex, a vector of human disease, has evolved to be resistant to insecticides
      by a limited number of amino acid substitutions in AChE1, which is encoded by the
      ace-1 gene. The aims of this study are to identify single nucleotide polymorphism
      (SNP) sites in the ace-1 gene of the C. pipiens complex and explore an economical
      high-throughput method to differentiate the genotypes of these sites in
      mosquitoes collected in the field. We identified 22 SNP sites in exon regions of
      the ace-1 gene. Four of them led to non-synonymous mutations, that is, Y163C,
      G247S, C677S and T682A. We used matrix-assisted laser desorption ionization -
      time-of-flight mass spectrometry for genotyping at these four sites and another
      site F416V, which was relevant to insecticide resistance, in 150 mosquitoes
      collected from 15 field populations. We were able to synchronize analysis of the
      five SNP sites in each well of a 384-well plate for each individual mosquito,
      thus decreasing the cost to one-fifth of the routine analysis. Heterozygous
      genotypes at Y163C and G247S sites were observed in one mosquito. The possible
      influence of the five SNP sites on the activity or function of the enzyme is
      discussed based on the predicted tertiary structure of the enzyme.

PMID- 23955858
TI  - Molecular identification and characterization of the Orco orthologue of
      Spodoptera litura.
AB  - A highly conserved and broadly expressed receptor protein Orco (olfactory
      coreceptor) is crucial for insect olfaction, and an orthologue of Orco has been
      identified in several insect species. Here we report the identification and
      characterization of Orco from Spodoptera litura. The protein displays high
      primary amino acid sequence conservation with other previously identified Orco
      orthologues. Bioinformatic analysis revealed that it has common features with
      other members of the Orco subfamily: seven-transmembrane domains with
      intracellular N-terminus and extracellular C-terminus. The transcript was
      detected in abundance in the chemosensory organs of the antennae of both male and
      female adults by real-time polymerase chain reaction analysis, and was localized
      at the bases of all categories of olfactory sensilla through in situ
      hybridization.

PMID- 23955859
TI  - Heat shock protein genes (hsp20, hsp75 and hsp90) from Pieris rapae: molecular
      cloning and transcription in response to parasitization by Pteromalus puparum.
AB  - Most molecular work on the roles of heat shock proteins (hsps) in host-parasite
      interaction has focused on vertebrates, rather than invertebrates. Here the full
      length complementary DNA (cDNA) sequences of three hsp genes (hsp20, hsp75 and
      hsp90) were amplified from Pieris rapae, and their transcriptional responsiveness
      to parasitization by the endoparasitic wasp Pteromalus puparum were investigated.
      The cDNA sequence analysis of hsp20, hsp75 and hsp90 revealed open reading frames
      of 531, 2 328 and 2 157 bp in length, which encode proteins with calculated
      molecular weights of 19.5, 75.48 and 82.7 kDa, respectively. The comparison of
      amino acid sequences showed that P. rapae hsp20 shared highly divergent homology
      to that of other insects, while hsp75 and hsp90 showed high homology to their
      counterparts of other species. The expression analysis indicated that these three
      genes were influenced in response to parasitization by P. puparum. The hsp20
      transcripts in parasitized pupae were higher compared to non-parasitized pupae.
      The expression of hsp75 and hsp90 were down-regulated following parasitization.
      The results indicate that hsps are involved in host-parasitoid interactions.

PMID- 23955860
TI  - Diversity of secondary endosymbionts among different putative species of the
      whitefly Bemisia tabaci.
AB  - Endosymbionts are important components of arthropod biology. The whitefly Bemisia
      tabaci (Gennadius) (Hemiptera: Aleyrodidae) is a cryptic species complex composed
      of >= 28 putative species. In addition to the primary endosymbiont Portiera
      aleyrodidarum, six secondary endosymbionts (S-endosymbionts), Hamiltonella,
      Rickettsia, Wolbachia, Cardinium, Arsenophonus and Fritschea, have been
      identified in B. tabaci thus far. Here, we tested five of the six S-endosymbiont
      lineages (excluding Fritschea) from 340 whitely individuals representing six
      putative species from China. Hamiltonella was detected only in the two exotic
      invaders, Middle East-Asia Minor 1 (MEAM1) and Mediterranean (MED). Rickettsia
      was absent in Asia II 1 and MED, scarce in Asia II 3 (13%), but abundant in Asia
      II 7 (63.2%), China 1 (84.7%) and MEAM1 (100%). Wolbachia, Cardinium and
      Arsenophonus were absent in the invasive MEAM1 and MED but mostly abundant in the
      native putative species. Furthermore, phylogenetic analyses revealed that some S
      endosymbionts have several clades and different B. tabaci putative species can
      harbor different clades of a given S-endosymbiont, demonstrating further the
      complexity of S-endosymbionts in B. tabaci. All together, our results demonstrate
      the variation and diversity of S-endosymbionts in different putative species of
      B. tabaci, especially between invasive and native whiteflies.

PMID- 23955861
TI  - Comparative analysis of Solanum stoloniferum responses to probing by the green
      peach aphid Myzus persicae and the potato aphid Macrosiphum euphorbiae.
AB  - Plants protect themselves against aphid attacks by species-specific defense
      mechanisms. Previously, we have shown that Solanum stoloniferum Schlechtd has
      resistance factors to Myzus persicae Sulzer (Homoptera: Aphididae) at the
      epidermal/mesophyll level that are not effective against Macrosiphum euphorbiae
      Thomas (Homoptera: Aphididae). Here, we compare the nymphal mortality, the pre
      reproductive development time, and the probing behavior of M. persicae and M.
      euphorbiae on S. stoloniferum and Solanum tuberosum L. Furthermore, we analyze
      the changes in gene expression in S. stoloniferum 96 hours post infestation by
      either aphid species. Although the M. euphorbiae probing behavior shows that
      aphids encounter more probing constrains on phloem activities-longer probing and
      salivation time- on S. stoloniferum than on S. tuberosum, the aphids succeeded in
      reaching a sustained ingestion of phloem sap on both plants. Probing by M.
      persicae on S. stoloniferum plants resulted in limited feeding only. Survival of
      M. euphorbiae and M. persicae was affected on young leaves, but not on senescent
      leaves of S. stoloniferum. Infestation by M. euphorbiae changed the expression of
      more genes than M. persicae did. At the systemic level both aphids elicited a
      weak response. Infestation of S. stoloniferum plants with a large number of M.
      persicae induced morphological changes in the leaves, leading to the development
      of pustules that were caused by disrupted vascular parenchyma and surrounding
      tissue. In contrast, an infestation by M. euphorbiae had no morphological
      effects. Both plant species can be regarded as good host for M. euphorbiae,
      whereas only S. tuberosum is a good host for M. persicae and S. stoloniferum is
      not. Infestation of S. stoloniferum by M. persicae or M. euphorbiae changed the
      expression of a set of plant genes specific for each of the aphids as well as a
      set of common genes.

PMID- 23955862
TI  - Pollinating fig wasp Ceratosolen solmsi adjusts the offspring sex ratio to other
      foundresses.
AB  - Local mate competition theory predicts that offspring sex ratio in pollinating
      fig wasps is female-biased when there is only one foundress, and increased
      foundress density results in increased offspring sex ratio. Information of other
      foundresses and clutch size have been suggested to be the main proximate
      explanations for sex ratio adjustment under local mate competition. Our focus was
      to show the mechanism of sex ratio adjustment in a pollinating fig wasp,
      Ceratosolen solmsi Mayr, an obligate pollinator of the functionally dioecious
      fig, Ficus hispida Linn., with controlled experiments in the field. First, we
      obtained offspring from one pollinator and offspring at different oviposition
      sequences, and found that offspring sex ratio decreased with clutch size, and
      pollinators produced most of their male offspring at the start of bouts, followed
      by mostly females. Second, we found that offspring sex ratio increased with
      foundress density, and pollinators did adjust their offspring sex ratio to other
      females in the oviposition patches. We suggest that when oviposition sites are
      not limited, pollinators will mainly adjust their offspring sex ratio to other
      foundresses independent of clutch size changes, whereas adjusting clutch size may
      be used to adjust sex ratio when oviposition sites are limited.

PMID- 23955863
TI  - Adaptive strategies of overwintering adults: reproductive diapause and mating
      behavior in a grasshopper, Stenocatantops splendens (Orthoptera: Catantopidae).
AB  - To understand the adaptive strategies of the overwintering adults of
      Stenocatantops splendens, the mechanism of maintenance and termination of the
      reproductive diapause, the variation in mortality between overwintering females
      and males, and the mating strategy of the males were investigated. The results
      indicated that the adult reproductive diapause in natural conditions was mainly
      regulated by photoperiod in the fall - long photoperiods promoted reproductive
      development and short photoperiods maintained reproductive diapause, and the
      sensitivity of the overwintering adults to photoperiod was over before the end of
      the winter. When transferred from natural conditions to controlled laboratory
      conditions on dates from September through February, pre-oviposition became
      increasingly shorter with increasingly deferred transfer dates regardless of
      photoperiod conditions. The adults treated with low temperature for 30 days in
      September through November had significantly shorter pre-oviposition, suggesting
      that low temperatures in winter had an important role in the termination of
      reproductive diapause. The female had a significantly lower supercooling point
      than the male, which was related to their lower mortality after winter. In
      addition, observations of wild populations of the species indicated that mating
      behavior prior to winter and the duration of pre-mating period were not affected
      by photoperiod; mating and sperm transfer were mostly completed by November.
      Compared with females only mating before winter, females mating in the spring had
      shorter life span, longer pre-oviposition, lower hatching rate and laid fewer egg
      pods while showing no significant difference with regard to ovipositional
      interval, per pod number of eggs and nymph dry weight.

PMID- 23955864
TI  - Population specific fitness response of Drosophila subobscura to lead pollution.
AB  - Differences in heavy metal tolerance among separate populations of the same
      species have often been interpreted as local adaptation. Persistence of
      differences after removing the stressor indicates that mechanisms responsible for
      the increased tolerance were genetically determined. Drosophila subobscura Collin
      (Diptera: Drosophilidae) populations were sampled from two localities with
      different history of heavy metal pollution, and reared for eight generations in
      the laboratory on a standard medium and on media with different concentrations of
      lead (Pb). To determine whether flies from different natural populations exposed
      to the Pb-contaminated media in the laboratory show population specific
      variability in fitness components over generations, experimental groups with
      different concentrations of lead were assayed in three generations (F2 , F5 , and
      F8 ) for fecundity, developmental time, and egg-to-adult viability. On the
      contaminated medium, fecundity was reduced in later generations and viability was
      increased, irrespective of the environmental origin of populations. For both
      populations, developmental time showed a tendency of slowing down on media with
      lead. Faster development was observed in later generations. Preadaptation to
      contamination, meaning higher fecundity, higher viability, and faster egg to
      adult development in all studied generations, was found in D. subobscura
      originating from the locality with a higher level of heavy metal pollution.

PMID- 23955865
TI  - Data Processing System (DPS) software with experimental design, statistical
      analysis and data mining developed for use in entomological research.
AB  - A comprehensive but simple-to-use software package called DPS (Data Processing
      System) has been developed to execute a range of standard numerical analyses and
      operations used in experimental design, statistics and data mining. This program
      runs on standard Windows computers. Many of the functions are specific to
      entomological and other biological research and are not found in standard
      statistical software. This paper presents applications of DPS to experimental
      design, statistical analysis and data mining in entomology.

PMID- 23955871
TI  - Binocular symmetry/asymmetry of scleral redness as a cue for sadness,
      healthiness, and attractiveness in humans.
AB  - Among primates, only humans have the white sclerae that provide the ground
      necessary to display their own color and that of the overlying conjunctiva.
      Scleral color, primarily redness, provides cues of socially and biologically
      significant information about an individual. The present study examines the
      effect of the asymmetry of binocular scleral redness on perceived sadness,
      healthiness, and attractiveness by contrasting ratings of images of individuals
      who had one, both, or neither sclera reddened by digital editing. Building upon
      previous research, this study further defines the details of the scleral color
      display and contributes to the more general issue of facial and body symmetry,
      predictors of phenotypic condition and genotypic quality that are of interest to
      evolutionary theorists. Individuals with binocular and monocular redness were
      rated as sadder, less healthy, and less attractive than those with untinted
      control sclerae, with ratings corresponding to the degree of redness or
      whiteness. Bilaterally symmetrical (binocular) scleral redness or whiteness
      provided anchorage points for ratings, with ratings for bilaterally asymmetrical
      (monocular) redness or whiteness falling between them; there was no unique effect
      of asymmetry. 

PMID- 23955873
TI  - A multidimensional approach to the analysis of chemical shift titration
      experiments in the frame of a multiple reaction scheme.
AB  - We present a method for fitting curves acquired by chemical shift titration
      experiments, in the frame of a three-step complexation mechanism. To that end, we
      have implemented a fitting procedure, based on a nonlinear least squares fitting
      method, that determines the best fitting curve using a "coarse grid search"
      approach and provides distributions for the different parameters of the
      complexation model that are compatible with the experimental precision. The
      resulting analysis protocol is first described and validated on a theoretical
      data set. We show its ability to converge to the true parameter values of the
      simulated reaction scheme and to evaluate complexation constants together with
      multidimensional uncertainties. Then, we apply this protocol to the study of the
      supramolecular interactions, in aqueous solution, between a lanthanide complex
      and three different model molecules, using NMR titration experiments. We show
      that within the uncertainty that can be evaluated from the parameter
      distributions generated during our analysis, the affinities between the
      lanthanide derivative and each model molecule can be discriminated, and we
      propose values for the corresponding thermodynamic constants.

PMID- 23955872
TI  - Use of novel technology-based techniques to improve alcohol-related outcomes in
      clinical trials.
AB  - With a better understanding of the biologic basis of alcohol dependence and the
      considerable financial burden of alcohol abuse and dependence, the number of
      alcohol-related clinical pharmacotherapy trials has been on the rise.
      Subsequently, the potential to find efficacious treatments is more promising.
      Unfortunately, alcohol-related trials face a number of challenges, as a result of
      the difficulties that arise from traditional and outdated methods to collect data
      and ensure medication adherence. Novel technology-based assessments, such as
      ecological momentary assessment, interactive voice response, transdermal sensor
      and medication-event monitoring system provide a prospective solution-albeit not
      without possible concerns-to the difficulties faced in alcohol-related clinical
      trials. Clinical trials are meant to define the efficacy of the treatment and to
      determine an effective and safe dosage. However, due to lack of adherence a drug
      could inappropriately or mistakenly be judged as ineffective for treating a
      specific disorder. The described technologies may be important tools to prevent
      false negatives in validating drug efficacy, to provide consistency in clinical
      trials and to improve available data regarding the study of pharmacotherapies for
      alcohol dependence. 

PMID- 23955874
TI  - Competing two enzymatic reactions realizing one-step preparation of cell
      enclosing duplex microcapsules.
AB  - The usefulness of cell-enclosing microcapsules in biomedical and
      biopharmaceutical fields is widely recognized. In this study, we developed a
      method enabling the preparation of microcapsules with a liquid core in one step
      using two enzymatic reactions, both of which consume H2 O2 competitively. The
      microcapsule membrane prepared in this study is composed of the hydrogel obtained
      from an alginate derivative possessing phenolic hydroxyl moieties (Alg-Ph). The
      cell-enclosing microcapsules with a hollow core were obtained by extruding an
      aqueous solution of Alg-Ph containing horseradish peroxidase (HRP), catalase, and
      cells into a co-flowing stream of liquid paraffin containing H2 O2 . Formation of
      the microcapsule membrane progressed from the surface of the droplets through HRP
      catalyzed cross-linking of Ph moieties by consuming H2 O2 supplied from the
      ambient liquid paraffin. A hollow core structure was induced by catalase
      catalyzed decomposition of H2 O2 resulting in the center region being at an
      insufficient level of H2 O2 . The viability of HeLa cells was 93.1% immediately
      after encapsulation in the microcapsules with about 250 um diameter obtained from
      an aqueous solution of 2.5% (w/v) Alg-Ph, 100 units mL(-1) HRP, 9.1 * 10(4) units
      mL(-1) catalase. The enclosed cells grew much faster than those in the
      microparticles with a solid core. In addition, the thickness of microcapsule
      membrane could be controlled by changing the concentrations of HRP and catalase
      in the range of 13-48 um. The proposed method could be versatile for preparing
      the microcapsules from the other polymer derivatives of carboxymetylcellulose and
      gelatin.

PMID- 23955875
TI  - Stress reactions and coping strategies among Bedouin Arab adolescents exposed to
      demolition of houses.
AB  - The aim of this study was to examine emotional reactions and coping strategies of
      Bedouin adolescents against the backdrop of house demolitions in the unrecognized
      Bedouin villages in the Negev, Israel. We compared two groups of adolescents
      living in unrecognized Bedouin villages, teenagers whose houses had been
      destroyed (acute + chronic group) and their counterparts whose houses had not
      been destroyed (chronic group). Data were gathered during October to December
      2010 from 465 Bedouin adolescents aged 13-18 years. Adolescents filled out self
      report questionnaires, which included demographics, objective and subjective
      exposure to house demolition, state anxiety, state anger, psychological distress
      and Adolescent Coping Scale. Results show differences between the two groups in
      stress reactions as well as in objective exposure to house demolition with the
      acute + chronic group reporting more stress and more exposure. In addition,
      different variables explained stress reactions in the different groups. Whereas
      in the acute + chronic group, objective and subjective exposure were the most
      significant variables, in the chronic group, the coping strategies explained
      stress with more variance. Results are discussed in terms of differentiating
      between types of stress, chronic versus acute + chronic and in relation to the
      interactionist model of coping with stress.

PMID- 23955876
TI  - Water-splitting catalysis and solar fuel devices: artificial leaves on the move.
AB  - The development of new energy materials that can be utilized to make renewable
      and clean fuels from abundant and easily accessible resources is among the most
      challenging and demanding tasks in science today. Solar-powered catalytic water
      splitting processes can be exploited as a source of electrons and protons to make
      clean renewable fuels, such as hydrogen, and in the sequestration of CO2 and its
      conversion into low-carbon energy carriers. Recently, there have been tremendous
      efforts to build up a stand-alone solar-to-fuel conversion device, the
      "artificial leaf", using light and water as raw materials. An overview of the
      recent progress in electrochemical and photo-electrocatalytic water splitting
      devices is presented, using both molecular water oxidation complexes (WOCs) and
      nano-structured assemblies to develop an artificial photosynthetic system. 

PMID- 23955877
TI  - Genetic relationships of introduced Colorado potato beetle Leptinotarsa
      decemlineata populations in Xinjiang, China.
AB  - The Colorado potato beetle (CPB), Leptinotarsa decemlineata (Say), is an infamous
      invasive species worldwide that aggressively attacks potato and other Solanaceae
      crops. CPB was first found in China in 1993 and has since spread across 2.77 *
      10(5) km(2) in Xinjiang Uygur Autonomous Region. To better understand genetic
      variation and migration patterns, we used seven polymorphic microsatellite loci
      to elucidate the genetic relationships and gene flow among 10 CPB populations
      across Xinjiang. (i) Overall low levels of genetic diversity were detected on the
      entire population in Xinjiang but most of the diversity was retained among
      populations during invasion. (ii) The mean pairwise FST was low (0.071 +/- 0.043)
      among populations. The genetic differentiation was little (pairwise FST 0.038 +/-
      0.016) between the five interior populations (Wusu, Urumqi, Jimsar, Qitai and
      Mulei) and Tacheng population. The six populations might come from the same
      genetic group via Bayesian clustering and were closely related on a neighbor
      joining tree. Combining the history data, the five interior populations may have
      originated from Tacheng. (iii) Gene flow was frequent, especially among the five
      interior populations. Individuals from the interior populations could be assigned
      to Tacheng at higher probabilities (means 0.518 +/- 0.127) than vice versa (means
      0.328 +/- 0.074), suggesting that the beetle population has spread from the
      border to the interior in Xinjiang. 

PMID- 23955878
TI  - Hydrocortisone effect on hyaluronate synthesis in a self-assembled human dermal
      equivalent.
AB  - Human dermal matrix is a 'self-assembled' dermal equivalent containing large
      amounts of the glycosaminoglycan hyaluronic acid (hyaluronate, hyaluronan, HA).
      We sought to investigate the actions of the hormone hydrocortisone on hyaluronate
      synthesis in the human dermal matrix. To this end, human dermal fibroblasts were
      cultured under serum-free conditions, and in the absence of a three-dimensional
      matrix, in the presence of varying amounts of hydrocortisone. The resultant human
      dermal matrices were characterized. We report that low concentrations of
      hydrocortisone enhance hyaluronate synthesis in the human dermal equivalent and
      higher concentrations cause inhibition of hyaluronate synthesis. Other
      glycosaminoglycan (chondroitin sulphate) synthesis is not affected by changing
      hydrocortisone concentrations up to 500* (200 ug/ml) of the base value. In order
      to gain preliminary insight into the molecular mechanism of hyaluronate
      inhibition, a differential gene array analysis was conducted of human dermal
      matrix grown in the presence of 200 ug/ml hydrocortisone and in a physiological
      concentration (0.4 ug/ml, normal conditions). The results of these experiments
      demonstrate the differential expression of 43 genes in the 500* (200 ug/ml)
      hydrocortisone construct as compared to the construct grown under normal
      conditions (0.4 ug/ml hydrocortisone). These preliminary experiments suggest that
      hydrocortisone at higher concentrations may exert its inhibitory effect on
      hyaluronate synthesis early in the glycolytic pathway, leading to HA biosynthesis
      by downregulation of phosphoglucomutase and glucose phosphate isomerase, possibly
      leading to depletion of the cellular pool of UDP-sugar precursors necessary for
      HA synthesis. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 23955879
TI  - Reevaluating the conceptual framework for applied research on host-plant
      resistance.
AB  - Applied research on host-plant resistance to arthropod pests has been guided over
      the past 60 years by a framework originally developed by Reginald Painter in his
      1951 book, Insect Resistance in Crop Plants. Painter divided the "phenomena" of
      resistance into three "mechanisms," nonpreference (later renamed antixenosis),
      antibiosis, and tolerance. The weaknesses of this framework are discussed. In
      particular, this trichotomous framework does not encompass all known mechanisms
      of resistance, and the antixenosis and antibiosis categories are ambiguous and
      inseparable in practice. These features have perhaps led to a simplistic approach
      to understanding arthropod resistance in crop plants. A dichotomous scheme is
      proposed as a replacement, with a major division between resistance (plant traits
      that limit injury to the plant) and tolerance (plant traits that reduce amount of
      yield loss per unit injury), and the resistance category subdivided into
      constitutive/inducible and direct/indirect subcategories. The most important
      benefits of adopting this dichotomous scheme are to more closely align the basic
      and applied literatures on plant resistance and to encourage a more mechanistic
      approach to studying plant resistance in crop plants. A more mechanistic approach
      will be needed to develop novel approaches for integrating plant resistance into
      pest management programs.

PMID- 23955880
TI  - Priming of antiherbivore defensive responses in plants.
AB  - Defense priming is defined as increased readiness of defense induction. A growing
      body of literature indicates that plants (or intact parts of a plant) are primed
      in anticipation of impending environmental stresses, both biotic and abiotic, and
      upon the following stimulus, induce defenses more quickly and strongly. For
      instance, some plants previously exposed to herbivore-inducible plant volatiles
      (HIPVs) from neighboring plants under herbivore attack show faster or stronger
      defense activation and enhanced insect resistance when challenged with secondary
      insect feeding. Research on priming of antiherbivore defense has been limited to
      the HIPV-mediated mechanism until recently, but significant advances were made in
      the past three years, including non-HIPV-mediated defense priming, epigenetic
      modifications as the molecular mechanism of priming, and others. It is timely to
      consider the advances in research on defense priming in the plant-insect
      interactions.

PMID- 23955881
TI  - Emerging role of roots in plant responses to above ground insect herbivory.
AB  - Plants have evolved complex biochemical mechanisms to counter threats from insect
      herbivory. Recent research has revealed an important role of roots in plant
      responses to above ground herbivory (AGH). The involvement of roots is integral
      to plant resistance and tolerance mechanisms. Roots not only play an active role
      in plant defenses by acting as sites for biosynthesis of various toxins and but
      also contribute to tolerance by storing photoassimilates to enable future
      regrowth. The interaction of roots with beneficial soil-borne microorganisms also
      influences the outcome of the interaction between plant and insect herbivores.
      Shoot-to-root communication signals are critical for plant response to AGH. A
      better understanding of the role of roots in plant response to AGH is essential
      in order to develop a comprehensive picture of plant-insect interactions. Here,
      we summarize the current status of research on the role of roots in plant
      response to AGH and also discuss possible signals involved in shoot-to-root
      communication.

PMID- 23955882
TI  - The evolutionary strategies of plant defenses have a dynamic impact on the
      adaptations and interactions of vectors and pathogens.
AB  - Plants have evolved and diversified to reduce the damages imposed by infectious
      pathogens and herbivorous insects. Living in a sedentary lifestyle, plants are
      constantly adapting to their environment. They employ various strategies to
      increase performance and fitness. Thus, plants developed cost-effective
      strategies to defend against specific insects and pathogens. Plant defense,
      however, imposes selective pressure on insects and pathogens. This selective
      pressure provides incentives for pathogens and insects to diversify and develop
      strategies to counter plant defense. This results in an evolutionary arms race
      among plants, pathogens and insects. The ever-changing adaptations and
      physiological alterations among these organisms make studying plant-vector
      pathogen interactions a challenging and fascinating field. Studying plant defense
      and plant protection requires knowledge of the relationship among organisms and
      the adaptive strategies each organism utilize. Therefore, this review focuses on
      the integral parts of plant-vector-pathogen interactions in order to understand
      the factors that affect plant defense and disease development. The review
      addresses plant-vector-pathogen co-evolution, plant defense strategies,
      specificity of plant defenses and plant-vector-pathogen interactions. Improving
      the comprehension of these factors will provide a multi-dimensional perspective
      for the future research in pest and disease management. 

PMID- 23955883
TI  - High basal defense gene expression determines sorghum resistance to the whorl
      feeding insect southwestern corn borer.
AB  - Southwestern corn borer (SWCB, Diatraea grandiosella) and fall armyworm (FAW,
      Spodoptera frugiperda) are major pests of sorghum in the southern United States.
      Host plant resistance is a desirable means for reducing plant damage and yield
      losses from both insects. In this study, we evaluated 12 sorghum lines for whorl
      stage resistance to leaf-feeding SWCB and FAW in greenhouse and laboratory
      bioassays. Differential plant responses were detected against the two insects.
      Among 12 lines tested, CM1821, Della and PI196583 were resistant to both insects,
      while BTx2752 was largely susceptible. Line R.09110 was resistant to SWCB, but
      susceptible to FAW, whereas Redbine-60 was susceptible to SWCB, but not to FAW.
      In addition, we quantified various chemical components in the plants and
      determined their association with insect resistance. Tannin and chlorophyll in
      leaves did not show any significant correlation with resistance to either
      insects, but contents of soluble protein in general were negatively correlated
      with resistance to both insects. Endogenous soluble sugar and dhurrin were only
      positively correlated with resistance to SWCB, but not with FAW resistance. To
      gain some molecular insight into resistance mechanism of sorghum to SWCB, we
      performed qPCR reactions for key genes encoding enzymes involved in dhurrin and
      jasmonic acid (JA) biosynthesis on selected resistant or susceptible lines.
      Although these genes were rapidly and strongly induced by insect feeding in all
      lines, the observed resistance is likely explained by higher constitutive dhurrin
      contents in some resistant lines and higher basal JA biosynthesis in others. Our
      results suggest that sorghum utilizes multiple strategies to defend itself
      against SWCB.

PMID- 23955884
TI  - Aflatoxin B1: toxicity, bioactivation and detoxification in the polyphagous
      caterpillar Trichoplusia ni.
AB  - Trichoplusia ni caterpillars are polyphagous foliage-feeders and rarely likely to
      encounter aflatoxin B1 (AFB1), a mycotoxin produced by Aspergillus flavus and A.
      parasiticus, in their host plants. To determine how T. ni copes with AFB1, we
      evaluated the toxicity of AFB1 to T. ni caterpillars at different developmental
      stages and found that AFB1 tolerance significantly increases with larval
      development. Diet incorporation of AFB1 at 1 MUg/g completely inhibited larval
      growth and pupation of newly hatched larvae, but 3 MUg/g AFB1 did not have
      apparent toxic effects on larval growth and pupation of caterpillars that first
      consume this compound 10 days after hatching. Piperonyl butoxide, a general
      inhibitor of cytochrome P450 monooxygenases (P450s), reduced the toxicity of
      AFB1, suggesting that AFB1 is bioactivated in T. ni and this bioactivation is
      mediated by P450s. Some plant allelochemicals, including flavonoids such as
      flavones, furanocoumarins such as xanthotoxin and imperatorin, and
      furanochromones such as visnagin, that induce P450s in other lepidopteran larvae
      ameliorated AFB1 toxicity, suggesting that P450s are also involved in AFB1
      detoxification in T. ni.

PMID- 23955885
TI  - Various infection status and molecular evidence for horizontal transmission and
      recombination of Wolbachia and Cardinium among rice planthoppers and related
      species.
AB  - Wolbachia and Cardinium are widely distributed and are considered important for
      their ability to disturb reproduction and affect other fitness-related traits of
      their hosts. By using multilocus sequence typing (MLST), RFLP (restriction
      fragment length polymorphism) and 16S ribosomal DNA gene sequencing methods, we
      extensively surveyed Wolbachia and Cardinium infection status of four predominant
      rice planthoppers and one kind of leafhopper in different rice fields. The
      results demonstrated that Sogatella furcifera (Horvath) and Laodelphax
      striatellus (Fallen) were infected with the same Wolbachia strain (wStri), while
      Nilaparvata lugens (Stal) and its closely related species Nilaparvata muiri China
      were infected with two phylogeneticlly distant strains, wLug and wMui,
      respectively. Three new Wolbachia strains (provisionally named wMfas1, wMfas2 and
      wMfas3) were detected in the leafhopper Macrosteles fascifrons (Stal). Only S.
      furcifera was co-infected with Cardinium, which indicated that the distribution
      of Cardinium in these rice planthoppers was narrower than that of Wolbachia.
      Unambiguous intragenic recombination events among these Wolbachia strains and
      incongruent phylogenetic relationships show that the connections between
      different Wolbachia strains and hosts were more complex than we expected. These
      results suggest that horizontal transmission and host associated specialization
      are two factors affecting Wolbachia and Cardinium infections among planthoppers
      and their related species.

PMID- 23955886
TI  - Mitochondrial DNA suggests a single maternal origin for the widespread triploid
      parthenogenetic pest species, Paratanytarsus grimmii, but microsatellite
      variation shows local endemism.
AB  - Parthenogenesis is common among invasive pest species, with many parthenogenetic
      species also showing polyploidy. Parthenogenetic polyploid species often have
      multiple hybrid origins and the potential to rapidly spread over vast
      geographical areas. In this study, we examine patterns of mitochondrial and
      microsatellite variation in a widespread triploid parthenogenetic chironomid pest
      species, Paratanytarsus grimmii. Based on samples from five countries, including
      Australia, England, Germany, Japan, and Canada, we found extremely low
      mitochondrial diversity (<0.14%), with most individuals sharing a common and
      widespread haplotype. In contrast, microsatellite diversity revealed 41 clonal
      variants, which were regionally endemic. These findings suggest a single invasive
      maternal lineage of P. grimmii is likely to have recently spread over a broad
      geographical range. High levels of genotypic endemism suggest P. grimmii
      populations have remained relatively isolated after an initial spread, with
      little ongoing migration. This, in part, can be attributed to rapid genetic
      differentiation via mutations of common clonal genotypes after P. grimmii spread,
      but multiple polyploidization and subsequent founder events are also likely to be
      contributing factors.

PMID- 23955887
TI  - Does cypermethrin affect enzyme activity, respiration rate and walking behavior
      of the maize weevil (Sitophilus zeamais)?
AB  - Insecticides cause a range of sub-lethal effects on targeted insects, which are
      frequently detrimental to them. However, targeted insects are able to cope with
      insecticides within sub-lethal ranges, which vary with their susceptibility. Here
      we assessed the response of three strains of the maize weevil Sitophilus zeamais
      Motschulsky (Coleoptera: Curculionidae) to sub-lethal exposure to the pyrethoid
      insecticide cypermethrin. We expected enzyme induction associated with
      cypermethrin resistance since it would aid the resistant insects in surviving
      such exposure. Lower respiration rate and lower activity were also expected in
      insecticide-resistant insects since these traits are also likely to favor
      survivorship under insecticide exposure. Curiously though, cypermethrin did not
      affect activity of digestive and energy metabolism enzymes, and even reduced the
      activity of some enzymes (particularly for cellulase and cysteine-proteinase
      activity in this case). There was strain variation in response, which may be
      (partially) related to insecticide resistance in some strains. Sub-lethal
      exposure to cypermethrin depressed proteolytic and mainly cellulolytic activity
      in the exposed insects, which is likely to impair their fitness. However, such
      exposure did not affect respiration rate and walking behavior of the insects
      (except for the susceptible strain where walking activity was reduced). Walking
      activity varies with strain and may minimize insecticide exposure, which should
      be a concern, particularly if associated with (physiological) insecticide
      resistance. 

PMID- 23955888
TI  - Chemical and behavioral analysis of the cuticular hydrocarbons from Asian citrus
      psyllid, Diaphorina citri.
AB  - Huanglongbing (HLB) is the most destructive disease of citrus worldwide. The
      Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is the
      vector of the phloem-inhabiting bacterium, Candidatus Liberibacter asiaticus,
      which is presumed to cause HLB in Florida citrus. Laboratory and field studies
      were conducted to examine the behavioral responses of male and female D. citri to
      their cuticular extracts. In olfactometer assays, more male D. citri were
      attracted to one, five, or 10 female cuticular extract equivalent units than
      blank controls. The results were confirmed in field studies in which clear or
      yellow traps baited with 10 female cuticular extract equivalent units attracted
      proportionately more males than clear traps baited with male cuticular extract or
      unbaited traps. Analyses of cuticular constituents of male and female D. citri
      revealed differences between the sexes in chemical composition of their cuticular
      extracts. Laboratory bioassays with synthetic chemicals identified from cuticular
      extracts indicated that dodecanoic acid attracted more males than clean air.
      Traps baited with dodecanoic acid did not increase total catch of D. citri as
      compared with blank traps at the dosages tested; however, the sex ratio of
      psyllid catch was male biased on traps baited with the highest lure loading
      dosage tested (10.0 mg).

PMID- 23955889
TI  - Female-borne cues affecting Psyttalia concolor (Hymenoptera: Braconidae) male
      behavior during courtship and mating.
AB  - Knowledge of the mechanisms that regulate courtship and mating behavior in
      Psyttalia concolor (Szepligeti)-a koinobiont endophagous solitary parasitoid of
      the olive fruit fly, Bactrocera oleae (Rossi), and of other fruit flies-is
      essential to its mass rearing and management. Augmentative releases of P.
      concolor for olive fruit fly control started in the Mediterranean areas in the
      1950s and still continue with limited success. We determined the influence of
      visual and chemical cues on courtship and mating behavior of this braconid and
      the possible effect of the mating status of males and females in the perception
      of these cues. Our results suggest that integration of visual and chemical
      stimuli are fundamental for mate location and courtship. Indeed, the optimal
      response of the male was achieved when physical and chemical cues were
      simultaneously presented and vision and olfaction worked synergistically. 

PMID- 23955890
TI  - High temperature determines the ups and downs of small brown planthopper
      Laodelphax striatellus population.
AB  - Small brown planthopper, Laodelphax striatellus (Fallen) numbers usually drop
      sharply in the summer and revive quickly in the autumn. However, it is unclear
      whether and how the high temperature plays a role in this process. The effects of
      durations of heat exposure (33 degrees C) on life-history traits were examined
      here. Exposure of adults for 1 day during the oviposition stage led to a very low
      survival of nymphs. The average longevity of L. striatellus exposed for 1-31 days
      from oviposition was significantly longer than that of the control (27 degrees
      C). Short-term (1-5 days) heat exposure of the third instar nymphs did not
      significantly influence eclosion, but exposure of the fourth instar nymphs
      significantly increased eclosion. Lifespan from egg to adult was significantly
      lengthened when the third instar nymphs were exposed to heat for 2-15 days, or
      the fourth instar were exposed for 10 days. The preoviposition period was
      prolonged by heat exposure of the third or fourth instar nymphs. Short-term heat
      exposure of less than 3 days of the third or fourth instar nymphs did not
      restrict fecundity, but when the exposure duration exceeded 5 days the total eggs
      per female and hatchability decreased. Exposure to high temperature increased the
      brachypter rate of adults. In summary, low survival and slowing development under
      heat exposure resulted in population decline in the summer, and the relatively
      high fecundity and brachypter rate led to quick revival in autumn. Temperature in
      the summer determines the rise and fall in numbers of L. striatellus. 

PMID- 23955891
TI  - Using dung beetles to evaluate the effects of urbanization on Atlantic Forest
      biodiversity.
AB  - We used dung beetles to evaluate the impact of urbanization on insect
      biodiversity in three Atlantic Forest fragments in Londrina, Parana, Brazil. This
      study provides the first empirical evidence of the impact of urbanization on
      richness, abundance, composition and guild structure of dung beetle communities
      from the Brazilian Atlantic Forest. We evaluated the community aspects
      (abundance, richness, composition and food guilds) of dung beetles in fragments
      with different degrees of immersion in the urban matrix using pitfall traps with
      four alternative baits (rotten meat, rotten fish, pig dung and decaying banana).
      A total of 1 719 individuals were collected, belonging to 29 species from 11
      genera and six Scarabaeinae tribes. The most urban-immersed fragment showed a
      higher species dominance and the beetle community captured on dung presented the
      greatest evenness. The beetle communities were distinct with respect to the
      fragments and feeding habits. Except for the dung beetle assemblage in the most
      urbanized forest fragment, all others exhibited contrasting differences in
      species composition attracted to each bait type. Our results clearly show that
      the degree of urbanization affects Atlantic Forest dung beetle communities and
      that the preservation of forest fragments inside the cities, even small ones, can
      provide refuges for Scarabaeinae.

PMID- 23955892
TI  - Moth diversity in three biofuel crops and native prairie in Illinois.
AB  - The expanding demand for biofuel feedstock may lead to large-scale conscription
      of land for monoculture production of biofuel crops with concomitant substantial
      negative impacts on biodiversity. We compared moth diversity in light-trap
      samples from corn, miscanthus, switchgrass and native prairie, to determine
      whether there is an observable relationship between plant species diversity and
      moth abundance and diversity. Moth alpha diversity was highest in prairie and was
      higher in switchgrass than in the other two biofuel crops. Beta diversity
      generally was low among the biofuel crops, and prairie shared lower beta
      diversity with switchgrass than with corn or miscanthus. Analysis of variance
      showed no significant differences in moth abundance per species among treatments.
      The alpha and beta diversity index findings are consistent with those of other
      studies on arthropods in biofuel crops and provide evidence to suggest that large
      scale conversion of acreage to biofuel crops may have substantial negative
      effects on arthropod biodiversity both within the cropping systems and in the
      surrounding landscape. 

PMID- 23955893
TI  - Confidence interval of intrinsic optimum temperature estimated using
      thermodynamic SSI model.
AB  - The intrinsic optimum temperature for the development of ectotherms is one of the
      most important factors not only for their physiological processes but also for
      ecological and evolutional processes. The Sharpe-Schoolfield-Ikemoto (SSI) model
      succeeded in defining the temperature that can thermodynamically meet the
      condition that at a particular temperature the probability of an active enzyme
      reaching its maximum activity is realized. Previously, an algorithm was developed
      by Ikemoto (Tropical malaria does not mean hot environments. Journal of Medical
      Entomology, 45, 963-969) to estimate model parameters, but that program was
      computationally very time consuming. Now, investigators can use the SSI model
      more easily because a full automatic computer program was designed by Shi et al.
      (A modified program for estimating the parameters of the SSI model. Environmental
      Entomology, 40, 462-469). However, the statistical significance of the point
      estimate of the intrinsic optimum temperature for each ectotherm has not yet been
      determined. Here, we provided a new method for calculating the confidence
      interval of the estimated intrinsic optimum temperature by modifying the
      approximate bootstrap confidence intervals method. For this purpose, it was
      necessary to develop a new program for a faster estimation of the parameters in
      the SSI model, which we have also done.

PMID- 23955894
TI  - Residents' attitudes toward a smartphone policy for inpatient attending rounds.

PMID- 23955895
TI  - Vitrification of immature mouse oocytes by the modified-cut standard straw
      method.
AB  - The feasibility of using the modified-cut standard straw (M-CSS) method for the
      vitrification of immature mouse oocytes has been tested. The effects of different
      vitrification methods on oocyte survival, cytoskeletal organization, the
      distribution of cortical granules (CGs), and apoptosis have also been compared.
      Immature mouse oocytes were vitrified-thawed using electron microscope grid or M
      CSS method, and cultured to meiosis II (MII) stage. Oocyte development,
      cytoskeletal organization, CG distribution, and the expression of apoptosis
      related genes were evaluated. Rates of recovery (91.7 vs. 74.9%) and survival
      (89.0 vs. 62.6%) were significantly higher in M-CSS group than in EM grid group.
      The number of oocytes with normal chromosome alignment at the spindle and spindle
      morphology were similar in both groups. However, the actin cap was significantly
      degraded in EM grid groups (52.6 vs. 35.1%, respectively). Abnormal release of
      CGs also frequently occurred in EM grid groups (42.6 vs. 32.7%, respectively).
      Pro-apoptosis-related gene expression levels of Bax, caspase 3 were expressed
      lower than control in MII stage oocytes derived from M-CSS group; anti apoptosis
      related genes, survivin and heat shock factor-1 (Hsf-1) were slightly increased.
      However, all genes expression was significantly increased in MII stage oocytes
      derived from EM grid groups. Vitrification reduces the survival rate of immature
      mouse oocytes, alters cytoskeletal organization and CG distribution, and promotes
      apoptosis. However, these effects are less pronounced in vitrified oocytes
      generated by M-CSS than in those generated by EM grid method. Therefore, the
      novel M-CSS is a feasible approach for the cryopreservation of immature mouse
      oocytes. 

PMID- 23955896
TI  - Single-chain polymer self-assembly using complementary hydrogen bonding units.
AB  - A triblock copolymer containing the complementary hydrogen bonding recognition
      pair ureidoguanosine-diaminonaphthyridine (UG-DAN) as pendant functional groups
      is synthesized using ring-opening metathesis polymerization (ROMP). The
      norbornene-based DAN monomer is shown to allow for a controlled polymerization
      when polymerized in the presence of a modified-UG molecule that serves as a
      protecting group, subsequently allowing for the fabrication of functionalized
      triblock copolymers. The self-assembly of the copolymers was characterized using
      dynamic light scattering and (1) H NMR spectroscopy. It is demonstrated that the
      polymers self-assemble via complementary hydrogen bonding motifs even at low
      dilutions, indicating intramolecular interactions.

PMID- 23955897
TI  - The influence of female age on male mating preference and reproductive success in
      cabbage beetle, Colaphellus bowringi.
AB  - The influence of female age on male mating preference and reproductive success
      has been studied using a promiscuous cabbage beetle, Colaphellus bowringi Baly
      (Coleoptera: Chrysomelidae). In a simultaneous choice test, middle-aged females
      had significantly greater mating success than young and old females. In single
      pair trials, when paired with middle-aged virgin males, middle-aged females mated
      faster, copulated longer, and had greater fecundity and fertility than young or
      old females, while the longevity of males was not significantly affected by
      female age. This study on C. bowringi suggests that middle-aged females are more
      receptive to mating, which can result in the highest male reproductive success. 

PMID- 23955898
TI  - Addition of electrophilic radicals to 2-benzyloxyglycals: synthesis and
      functionalization of fluorinated alpha-C-glycosides and derivatives.
AB  - A new method for the synthesis of fluorinated alpha-C-glycosides is described.
      The reactions between highly electrophilic radicals (fluorinated or
      unfluorinated) and a 2-benzyloxyglucal or galactal provide 2-keto-D-arabino- or 2
      keto-D-lyxo-hexopyranosides through an addition/fragmentation process. Sodium
      borohydride mediated or Meerwein-Ponndorf-Verley (MPV) reduction of these
      compounds provides alpha-C-glycosides that feature appropriate anchoring groups
      for further synthetic elaboration. The presence of CF2 CO2 iPr or CF2 Br groups
      at the pseudo-anomeric position allows efficient reduction/olefination or Br/Li
      exchange/nucleophilic-addition sequences. These transformations open the way for
      the synthesis of fluorinated C-glycosidic analogues of glycoconjugates. 

PMID- 23955899
TI  - Impact of navigated-control assistance on performance, workload and situation
      awareness of experienced surgeons performing a simulated mastoidectomy.
AB  - BACKGROUND: Navigated control (NC) is an advanced image-guided navigation system
      that provides an additional control function to enhance patient safety. It
      automatically stops the surgical instrument if it comes close to critical
      anatomical structures that need to be protected during surgery. The purpose of
      this study was to explore the human performance consequences of computer-based
      navigated control assistance. METHODS: Seven experienced surgeons conducted a
      simulated mastoidectomy manually and with support of the NC system. The impact on
      surgical performance, workload and situation awareness was analysed. RESULTS: NC
      support led to a better quality of surgical outcome and a lower level of
      physiological effort during surgery. Cost effects were reflected in reduced time
      efficiency and an increased subjectively experienced workload. CONCLUSION: The
      results demonstrate the potential of NC support in terms of lower workload and
      enhanced patient safety. Cost effects might be reduced by remodelling the control
      function.

PMID- 23955901
TI  - [The epidemiology of malaria in Ordu between 2002 and 2011].
AB  - OBJECTIVE: Malaria is still an important public health problem both in Turkey and
      worldwide. In this research, we examined the epidemiology of malaria using the
      data provided by the Malaria Control Unit of the Infectious Disease Division of
      Ordu Health Directory, from the years 2002 to 2011. METHODS: The retrospective
      study was performed on data from the Provincial Health Directory. The cases were
      evaluated according to age groups, gender, locations, months and parasite
      species. RESULTS: In the last 10 year period, a total of 31,575 blood samples
      were evaluated and 6 malaria cases (0.02%) were detected. Positive cases were
      examined all patients aged 15 years old and over. Cases were found to be imported
      cases coming to Ordu from other countries. The agent in half of cases was found
      to be Plasmodium vivax; Plasmodium falciparum was determined in the other half.
      All P. falciparum cases were found to be imported cases coming to Ordu from
      abroad. CONCLUSION: In this study, determination of the state of information on
      malaria in Ordu was the target, with the aim of using these data to contribute to
      the epidemiological data of malaria in our country. In addition, the protective
      measures to be taken against the disease are thought to be helpful.

PMID- 23955900
TI  - Comparable survival for pediatric acute myeloid leukemia with poor-risk
      cytogenetics following chemotherapy, matched related donor, or unrelated donor
      transplantation.
AB  - BACKGROUND: We sought to better define the role of hematopoietic cell
      transplantation (HCT) in first remission (CR1) for high-risk pediatric acute
      myeloid leukemia (AML). PROCEDURES: Outcomes were compared among patients aged
      less than 21 years with cytogenetically defined poor-risk AML treated with
      chemotherapy, matched related (MRD), or unrelated donor (URD) transplantation in
      CR1. Poor-risk cytogenetics was defined as monosomy 7/del7q, monosomy 5/del 5q,
      abnormalities of 3q, t(6;9)(p23;q34), or complex karyotype. Included are patients
      treated on Children's Oncology Group trials or reported to the Center for
      International Blood and Marrow Transplant Research from 1989 to 2006. RESULTS: Of
      the 233 patients, 123 received chemotherapy, 55 received MRD HCT, and 55 received
      URD HCT. The 5-year overall survival from the time of consolidation chemotherapy
      or transplant conditioning was similar: chemotherapy (43% +/- 9%), MRD (46% +/-
      14%), or URD (50% +/- 14%), P = 0.99. Similarly, multivariate analysis
      demonstrated no significant differences in survival [(reference group =
      chemotherapy); MRD HR 1.08, P = 0.76; URD HR 1.13, P = 0.67] despite lower
      relapse risk with URD HCT (HR = 0.43, P = 0.01). CONCLUSIONS: Our findings do not
      provide support for the preferential use of HCT over chemotherapy alone for
      children with cytogenetically defined poor-risk AML in CR1.

PMID- 23955902
TI  - [Role of Dientamoeba fragilis and Blastocystis spp. in Irritable Bowel Syndrome].
AB  - OBJECTIVE: We investigated the prevalence of Dientamoeba fragilis and
      Blastocystis spp. in IBS patients and evaluated whether there was a possible link
      between IBS and these parasitic infections. METHODS: Stool specimens collected
      from 55 IBS patients, 80 patients with gastroenteritis as control group 1 (CG-1)
      and 50 healthy volunteers as control group 2 (CG-2) were included the study.
      Samples were examined by direct microscopy, trichrome staining and culture
      methods. RESULTS: While there was no significant difference in the prevalence of
      Blastocystis spp. between IBS patients and CG-1 (p > 0.05), a significant
      difference was found between IBS and CG-2 (p < 0.05). Patients with IBS were
      found to have five or more Blastocystis spp. per field than control groups. After
      eradication, all symptoms were cured in four patients, there were only
      constipation problems left in eleven patients and there were no changes in
      clinical findings in three patients. D. fragilis was not found in any of the
      samples. CONCLUSION: The reason we did not find any D. fragilis may be due to the
      low infection rate in the region. However, significantly having five or more
      Blastocystis spp. per field (X40) in IBS patients and regression of IBS symptoms
      after treatment in most of the patients suggested a possible link between IBS and
      Blastocystis spp.

PMID- 23955903
TI  - [Prevalence of Echinococcus granulosus determined with polymerase chain reaction
      in dogs in Aydin district].
AB  - OBJECTIVE: In this study, it was aimed to determine the prevalence of E.
      granulosus in the Aydin district. METHODS: Clean and fresh faeces samples were
      collected off the ground from owned dogs (n=100; 25 female, 75 male) with the
      range of 6-16 months old. These faeces samples were obtained in 13 villages from
      five different locations (Centre, Soke, Cine, Bozdogan and Kuyucak) of the Aydin
      district. The prevalence of E. granulosus was investigated with PCR and prior to
      applications of molecular techniques, faeces samples were investigated with
      macroscopic and floatation methods RESULTS: E. granulosus was determined in only
      one dog (1%; 1/100) and Toxocara canis (11%), Ancylostoma caninum (%3), Taenia
      spp. (2%) and Capillaria spp. (1%) eggs were also identified. CONCLUSION: Current
      prevalence (1%) of E. granulosus in this study is lower than the other studies
      conducted in different parts of Turkey. Determination of E. granulosus with PCR
      in faeces without determining any parasites with either macroscopic or
      microscopic examinations could indicate the potential risk of dog faeces for
      animal owners, veterinarians and parasitology laboratory technicians.

PMID- 23955904
TI  - [Cutaneous leishmaniasis and its status in Antalya, Turkey].
AB  - OBJECTIVE: Leishmaniasis is a group of diseases, in different clinical forms,
      caused by the intracellular protozoan parasites, Leishmania species. The disease
      is transmitted by a female sand fly infected with the parasite sucking blood from
      people. Cutaneous leishmaniasis (CL) is the most common form of the disease. The
      aim of this study is to examine the status of CL in the Antalya province and
      contribute to the prevention of the disease in this region. METHODS: The data of
      CL cases officially notified in the province between 2005 and 2012 were provided
      by the Basic Health Statistics Module of Ministry of Health. The cases were
      evaluated according to months, seasons, years, age groups, gender, and locations.
      RESULTS: Between 2005 and 2012, 220 CL cases were reported officially. Out of 220
      cases, 129 (58.64%) and 91 (41.36%) were male and female, respectively. One
      hundred and eighteen (53.64%) of the cases were in individuals under 20 years
      old. The highest rate of cases was determined in May (33 cases, 15%) and also
      during spring (75 cases, 34.09%), while the lowest rate was obtained in July (11
      cases, 5%) and also during summer (46 cases, 20.91%). It was determined that CL
      cases were generally reported from suburbs and villages of districts of the
      Antalya province. CONCLUSION: The number of cases has decreased in Antalya in
      recent years. However, the climate, nature, vegetation cover, socio-economic
      structure, population mobility and continuous notification of the cases from the
      certain areas of the province are considered significant risk factors. Therefore,
      health screenings, public health education and vector control applications should
      be regularly performed by sectorial cooperation throughout the year.

PMID- 23955905
TI  - A novel adjuvant, mixture of Alum and naltrexone, elicits humoral immune
      responses for excreted/secreted antigens of Toxoplasma gondii tachyzoites vaccine
      in Balb/c murine model.
AB  - OBJECTIVE: The excreted-secreted antigens (ESA) from the tachyzoites seem to play
      a key role in immunity against Toxoplasma gondii. The aim of this study is to
      investigate whether Alum-NLT mixture, as a new adjuvant, can induce humoral
      immunity in response to excreted secreted antigens (ESA) of Toxoplasma gondii as
      a model vaccine or not. METHODS: Six- to eight-week-old female Balb/c mice were
      divided into five groups. Mice in the experimental groups received either ESA
      vaccine alone or in combination with the adjuvant Alum, NLT or Alum-NLT mixture;
      Mice in the negative control group received phosphate buffered saline (PBS). All
      mice were immunised, three times subcutaneously (s.c.) with a total volume of
      150MUl each with a 10-day interval. Ten days after the final immunisation, immune
      response to Toxoplasma gondii was assessed. RESULTS: Our results revealed that
      Alum-NLT mixture as an adjuvant during vaccination boosts the efficacy of the ESA
      vaccine by means of increasing Toxoplasma gondii-specific IgG, IgG2a production
      and the ratio of IgG2a/IgG1 (P-value < 0.05). The use of this adjuvant mixture
      improved the protective immunity against Toxoplasma gondii. CONCLUSION:
      Administration of the Alum-NLT mixture as an adjuvant in ESA vaccine enhances
      humoral immunity.

PMID- 23955906
TI  - [The results of Hacettepe University Faculty of Medicine Parasitology Laboratory
      in 2003-2012: evaluation of 10 years].
AB  - OBJECTIVE: Parasitic diseases are common throughout the world. Evaluation of
      regional epidemiological data is needed to determine protective measures and
      treatment strategies. METHODS: This study evaluates the parasites detected in
      Hacettepe University Faculty of Medicine Parasitology Laboratory. RESULTS: Of the
      87,100 clinical samples evaluated in the study, 85,707 (98.4%) were from stool
      samples. Parasites were shown in 3,681 (4.2%) of the samples from 2,906 patients.
      The most common parasites were Giardia intestinalis (40%), Blastocystis spp.
      (22%), Entamoeba coli (12%), Dientamoeba fragilis (9%), Enterobius vermicularis
      (5%), Echinococcus spp. (4%) and Taenia spp. (3%) respectively. When distribution
      among years was evaluated, G. intestinalis, the most common parasite, had a
      tendency to decrease after 2004 whereas cases with Blastocystis spp. showed a
      clear increase in 2011 and 2012. The downward trend in parasite-positive cases
      also stopped in the last two years, in parallel to the increase of Blastocystis
      spp. During the study, Leishmania spp. and Plasmodium spp. were detected in four
      patients each. CONCLUSION: This study evaluated the results of a laboratory that
      scans a large number of patients in our region. Data obtained from different
      regions will allow to direct strategies to diagnose, treat and implement
      preventive measures against parasitic diseases in our country.

PMID- 23955907
TI  - Prevalence of hydatidosis in slaughtered animals in Iran.
AB  - OBJECTIVE: Hydatid cyst or cystic echincoccosis (CE) is an important medical and
      veterinary problem in the world, especially in Iran. Domestic intermediate hosts
      are a major reservoir for the disease in humans. The aim of this study was to
      determine the prevalence of hydatid cysts in slaughtered animals in Isfahan,
      central part of Iran. METHODS: In this cross-sectional study performed from 10
      May 2009 to 10 May 2010, a total of 196,325 animals (89,651 sheep, 93,050 goats,
      9,112 cattle and 4,512 calves) were inspected macroscopically for hydatid cysts.
      RESULTS: Prevalence rate of CE in sheep, goats, cattle and calf was 16.4%, 3.1%,
      6.5% and 8.2%, respectively. In all cases, the prevalence in female cattle and
      sheep was more than in males (P < 0.001). There are significant seasonal pattern
      for hydatidosis only in sheep (P < 0.001) and the highest prevalence of cysts was
      seen in autumn and winter seasons. The fertility of cysts in the liver of sheep
      (77%) was higher than in lungs (47.9%), but was higher in lungs in cattle (44%).
      Most condemnation cases were seen in lung of sheep (27.1%). CONCLUSION: It
      appears that sheep are the most important intermediate hosts for E. granolusus in
      this area.

PMID- 23955908
TI  - [An epidemiological study on canine leishmaniasis (CanL) and sand flies in
      Northern Cyprus].
AB  - OBJECTIVE: In this study, the investigation on the prevalence of canine
      leishmaniasis (CanL) and sand fly species incriminated as potential vectors of
      leishmaniasis in the northern part of the Cyprus were aimed. METHODS: This
      research was conducted in two periods; 2004 and 2012. Serological (IFAT and rK39)
      and molecular (PCR) tests were performed on 83 dog blood samples during the 2004
      survey. PCR was performed using primers 13A/13B targeting kinetoplastid
      minicircle constant region. Genomic Nested-PCR was applied using R221/R332 and
      R323/333 primers for 5 clinically suspected dog samples in 2012. Sand flies were
      collected from the Lapithos town and Kyreniae province using CDC light traps and
      midgut dissection was done for the presence of Leishmania parasites during the
      2012 survey. RESULTS: Three (3.61%) out of 83 dogs were found to be positive for
      CanL in 2004, while 3 out of 5 clinically suspected dogs were positive in 2012.
      In total 296 female sand flies were dissected and 9 species belonging to
      Phlebotomus and Sergentomyia genera were determined. No promastigote was found in
      the dissected females. CONCLUSION: The results obtained in two different periods
      showed that the importance and risk of canine disease are increasing in the
      northern Cyprus and further studies should be performed in northern Cyprus for
      determining the incidence of canine and human leishmaniasis.

PMID- 23955909
TI  - Seasonal changes of house dust mite population in Bitlis and Mus provinces of
      Turkey.
AB  - OBJECTIVE: This study was conducted to determine the dust mite fauna of houses in
      Bitlis and Mus provinces, the monthly value of mite numbers/g dust, as well as
      the impact of temperature, humidity and altitude on their numbers. METHODS: Dust
      samples were collected monthly from May 2010 to April 2011 from six houses
      belonging to three settlements; two of the houses were located in Bitlis, while
      another four were in Mus province. RESULTS: All 72 examined dust samples were
      found to be positive with regard to mites. The number of mites found in 1 g dust
      varied from 25 to 2,740. Overall, 1,167 house dust mites belonging to the orders
      Astigmata, Mesostigmata and Prostigmata were isolated. Dermatophagoides
      pteronyssinus was the predominant mite (83.2%), followed by Lepidoglyphus
      destructor (6.3%), Acarus siro (2.7%) and Tyrophagus putrescentiae (1.9%). The
      mite numbers were higher in the warmer months of the year. CONCLUSION: The
      dominant mite in the Bitlis and Mus provinces is Dermatophagoides pteronyssinus,
      and the highest mite numbers were found in months in which the outside humidity
      was low.

PMID- 23955910
TI  - On the occurrence of a Haemogregarinae (Apicomplexa) parasite from freshwater
      turtles of South 24 Parganas, West Bengal, India.
AB  - OBJECTIVE: The aim of this study was to investigate Haemogregarine parasites
      (Apicomplexa: Haemogregarinidae) of freshwater turtles (Lissemys punctata
      andersoni, Geoclemys hamiltonii) of India. METHODS: Turtles were collected by net
      from two ponds of South 24 Parganas, West Bengal, India. A small amount of blood
      was taken from the subcarapacial vein puncture site. The blood smears were
      prepared and air dried and fixed in absolute methyl alcohol. The slides were
      stained with Giemsa. RESULTS: Haemogregarine parasites were recorded from the
      erythrocytes of turtles. Multiple stages of intraerythrocytic gametocytes
      (microgametocytes, macrogametocytes, early schizonts and mature schizonts) were
      observed in blood films. CONCLUSION: It was found that only twenty out of the
      twenty five turtles (80%) were infected with the parasite. The prevalence rate
      was higher in larger turtles in comparison to smaller ones. It was also found
      that female turtles had a higher prevalence of infection than males.

PMID- 23955911
TI  - [Microsporidia and microsporidiosis].
AB  - All microsporidia are obligate parasites and have no active stages outside their
      host cells. Microsporidia lack some typical eukaryotic characteristics. There are
      now over 1200 species identified in 144 genera. The most familiar stage of
      microsporidia is the small, highly resistant spore, the size of which differs
      according to the species and is often 1-10 MUm. The general life cycle pattern of
      the microsporidia can be divided into three phases: the infective or
      environmental phase, the proliferative phase, and the sporogony or spore-forming
      phase. There are several methods for diagnosing microsporidia: light microscopic,
      transmission electron microscopy (TEM), immunofluorescence assays (IFA) and
      molecular methods. The clinical course of microsporidiosis depends on the immune
      status of the host and site of infection. Microsporidia can cause infections such
      as diarrhoea, keratitis, myositis, bronchitis and brochiolitis. Human
      microsporidiosis represents an important and rapidly emerging opportunistic
      disease, occurring mainly, but not exclusively, in severely immunocompromised
      patients with AIDS. The treatment of microsporidiosis is generally achieved with
      medications and supportive care. Depending on the site of infection and the
      microsporidia species involved, different medications are utilized. The most
      commonly used medications for microsporidiosis include albendazole and
      fumagillin.

PMID- 23955912
TI  - [The case of Henoch-Schonlein Purpura associated with Blastocystis hominis].
AB  - Blastocystis hominis (B. hominis) is a parasite that often causes
      gastrointestinal symptoms in patients with immune deficiency and has a
      controversial pathogenicity in healthy people, although some symptoms are
      reported outside of the gastrointestinal system in healthy persons. Henoch
      Schonlein Purpura (HSP) vasculitis is an acute autoimmune disease characterised
      by IgA storage of small vessels that is believed to include infectious factors in
      its aetiology. A 30-month follow-up with a boy diagnosed with HSP being treated
      with steroid therapy showed that he had recurrent symptoms within two days, and
      B. hominis was detected in the faecal analysis. His symptoms including rash,
      abdominal pain, and arthritis improved after treatment with steroid and co
      trimaksazol. This paper is the first to present a case of HSP associated with B.
      hominis.

PMID- 23955913
TI  - [Strongyloides stercoralis hyperinfection syndrome in a patient with Behcet's
      Disease].
AB  - Strongyloides stercoralis is endemic in the tropical and subtropical areas of the
      world. It is a soil-transmitted intestinal nematode affecting anywhere from 30 to
      100 million people worldwide. Strongyloides stercoralis is capable of causing
      autoinfection, which increases larval migration and proliferation in the host.
      This condition may lead to hyperinfection syndrome which has the potential to
      cause serious life threatening complications, especially in immunosuppressed
      patients. Thus, Strongyloides stercoralis hyperinfection syndrome should be
      suspected if there are clinical clues including gastrointestinal tract symptoms
      (abdominal pain, nausea, vomiting, diarrhoea), respiratory tract symptoms (cough,
      dyspnoea, wheezing, haemoptysis), skin symptoms (pruritus, erythema) and
      peripheral eosinophilia in a patient with underlying risk factors. Herein, we
      report a case of Strongyloides stercoralis hyperinfection syndrome in a patient
      with Behcet's Disease on immunosuppressive treatment.

PMID- 23955914
TI  - [Strongyloides stercoralis in a patient with ankylosing spondylitis: case
      report].
AB  - Strongyloidiasis is a nematode-borne disease caused by several Strongyloides
      species. This case was presented in order to indicate Strongyloidosis in
      immunocompromised patients with several clinical findings. A fifty-five year old
      male patient on corticosteroid medication for a long time because of ankylosing
      spondylitis was on infliximab medication for 5 years. He presented with swelling
      of his right foot for ten days, right shoulder stiffness and low back pain. The
      presence of anaemia was remarkable. S. stercoralis was reported in histological
      examination of endoscopic duodenal biopsy specimen. Peripheral blood smear showed
      68.4% neutrophils, 17% lymphocytes, 7.5% monocytes, and 6.7% (normal range 2%
      6.2) eosinophils. The level of IgE was raised: 285IU/mL (normal range 5
      120IU/mL). A large number of S. stercoralis larvae were detected upon stool
      examination with saline and iodine mounts and the formaldehyde ether
      concentration method. After treatment with two cure albendazole 400 mg/day for 7
      days, S. stercoralis larvae were not detected in stool examination. It is
      interesting that response to treatment was not observed on the first cure and the
      recovery was seen on the second cure. We suggest that hyperinfections should be
      taken into consideration in the diagnosis and treatment of immunocompromised
      patients with several complaints so that life-threatening effects of the nematode
      may be prevented.

PMID- 23955915
TI  - Coexistence of liver hydatid cyst and brucellosis in an adolescent.
AB  - A 15-year-old girl, who was evaluated for arthralgia of knees, was diagnosed as
      having brucellosis by serum agglutination and enzyme linked immunosorbent assay
      tests. Physical examination of the patient revealed massive hepatomegaly.
      Abdominal ultrasonography and computerised tomography showed a single large
      cystic lesion of the liver. The echinococcus indirect haemagglutination was
      positive at a titre of 1/1280. A giant hydatid cyst was removed with surgical
      intervention; in addition, she was treated with albendazole and antibrucellosis
      drug combination with success. Here, an immunocompetent adolescent case with
      brucellosis and concomitant hydatid cyst disease was reported to emphasise that
      the coexistence of both entities are infrequent but may occur due to increased
      prevalence of the diseases.

PMID- 23955916
TI  - Hepatic toxocariasis: a rare cause of right upper abdominal pain in the emergency
      department.
AB  - Toxocara canis and Toxocara cati are common helminths that reside in the
      intestinal tract of cats and dogs. Toxocariasis and, commonly, T. canis, is a
      disease commonly seen in children, which is characterised by hypereosinophilia,
      hepatomegaly, fever, transient pulmonary infiltration, and
      hypergammaglobulinaemia. Humans, who are not the actual host for these parasitic
      worms, are infected following oral intake of the infective eggs. Radiological
      differentiation of hepatic toxocariasis can be difficult, as liver lesions, which
      present as multiple hypoechoic lesions with regular borders, can look like a
      tumour, an infarction or an infection. We report on a case that presented to our
      emergency department (ED) with abdominal pain. During the initial review, the
      pathology in the liver was thought to be an infarction or an infection; however,
      the patient was diagnosed with hepatic toxocariasis following further evaluation.

PMID- 23955917
TI  - [A case report: hirudotherapy as a treatment modality in the microsurgery].
AB  - Medicinal leeches are known to inject more than 100 bioactive substances in the
      tissue whilst sucking blood. They are being successfully used for the treatment
      of diseases and symptoms, especially in plastic surgery. We report the case of a
      7-year old boy, who had lost the first phalanx of the middle finger of the right
      hand after an accident. The detached digit was replanted in the plastic surgery
      clinic, and treated within a period of 15 days with medicinal leeches (Hirudo
      medicinalis). Soon after the initiation of the hirudotherapy, the
      revascularisation of the re-attached phalanx, as well as the resolving of tissue
      oedema and pain was observed. Turkish physicians should be aware of the
      advantages of hirudotherapy in plastic and reconstructive surgery, especially in
      cases of detached digits and flaps.

PMID- 23955918
TI  - [Case of polyparasitism with long-term abdominal pain in a patient].
AB  - It is known that infections caused by intestinal protozoa and helminths affect
      over 3.5 million people worldwide. In this case report, a patient with complaints
      of stomach ache for a long time who received thermal treatment is presented.
      During this thermal treatment, diarrhoea occurred and multiparasitism was
      diagnosed with two helminths; pseudoparasitism and multiprotozoa, simultaneously.
      Stool samples were collected from the patient on three consecutive days and one
      day after the treatment. All of the samples were prepared with formalin-ether
      sedimentation techniques after macroscopic and direct microscopic investigation.
      Cellophane-tape method for Enterobius vermicularis and Taenia spp. and Erlich
      Ziehl-Neelsen staining method for coccidian parasites were used. At least four
      preparations were performed for each sample and serum physiologic, lugol'
      solution and trichrome stain were used for microscopic investigations.The motile
      segment she brought was investigated microscopically with Indian ink and
      identified as Taenia saginata. Under direct microscopy, Blastocystis hominis,
      Endolimax nana and Fasciola hepatica were seen. By formalin-ether sedimentation
      techniques, Ascaris lumbricoides, Fasciola hepatica, Blastocystis hominis,
      Endolimax nana and Entamoeba coli were identified. In recent years, intestinal
      parasitism is rarely seen in our city; therefore, multiparasitism in an adult and
      immunocompetent patient is interesting.

PMID- 23955919
TI  - [Four malaria-import patterns: sporadic region].
AB  - Malaria, as it has been during history, is an important parasitic infectious
      health problem nowadays. In Turkey, the most common kind of malaria is Plasmodium
      vivax, and P. falciparum is rarely observed in import events. After eradication
      activities started in 1926, the number of cases dramatically decreased in our
      country. However, the number of import cases is increasing as a result of
      tourism, migration, and deficiency in the eradication program. In tropical and
      sub-tropical regions and in endemic regions of Turkey such as South-Eastern
      Anatolia and Cukurova, in every feverish phenomenon, malaria is the first disease
      to be considered. The purpose of the present study is to evaluate clinical
      epidemiological characteristics of the four import patterns in foreign studies.

PMID- 23955920
TI  - Novel electric double-layer capacitor with a coaxial fiber structure.
AB  - A coaxial electric double-layer capacitor fiber is developed from the aligned
      carbon nanotube fiber and sheet, which functions as two electrodes with a polymer
      gel sandwiched between them. The unique coaxial structure enables a rapid
      transportation of ions between the two electrodes with a high electrochemical
      performance. These energy storage fibers are also flexible and stretchable, and
      can be woven into and widely used for electronic textiles. 

PMID- 23955921
TI  - The effect of Tyrophagus putrescentiae on Fusarium poae transmission and fungal
      community in stored barley in a laboratory experiment.
AB  - The effect of Tyrophagus putrescentiae on Fusarium poae transmission and fungal
      community composition was studied in nonsterile barley grain. The experiments
      included following treatments: control barley without mites; barley containing 10
      or 50 mites without preincubation on F. poae (Tp10 and Tp50); barley containing
      10 or 50 mites after preincubation on F. poae (FTp10 and FTp50). The number of
      mites, successful transfer of F. poae, and changes in the fungal communities were
      examined after 21 d of experiment. Increase of deoxynivalenol (DON) content in
      the barley was chosen as a criterion of successful F. poae transfer. The
      preincubation of T. putrescentiae on F. poae increased DON level approximately to
      800 and 300 MUg/kg of grain for FTp10 and FTp50, respectively. T. putrescentiae
      population growth in FTp10 was lower than in Tp10, while no difference was found
      between FTp50 and Tp50. Fungal communities were compared by amplification,
      cloning and sequencing of ITS fragments, and operational taxonomic units (OTU)
      analysis. The OTU analysis did not support the transfer of F. poae via mites.
      From the analyzed clones, only 13 cloned sequences clustered with F. poae in an
      OTU defined at distance level 0.07. The related clones originated from FTp10,
      Tp10, Tp50 and control treatments, but not from FTp50. However, the presence of
      F. poae in FTp50 was confirmed by PCR amplification with specific primers. The
      observation may be explained by different effect of mite population density, that
      is, in the high density, (FTp50 treatment) the fungus was overgrazed, while the
      lower population density (FTp10) supported F. poae transfer. 

PMID- 23955922
TI  - Atomistic understanding of the C.T mismatched DNA base pair tautomerization via
      the DPT: QM and QTAIM computational approaches.
AB  - It was established that the cytosine.thymine (C.T) mismatched DNA base pair with
      cis-oriented N1H glycosidic bonds has propeller-like structure (|N3C4C4N3| = 38.4
      degrees ), which is stabilized by three specific intermolecular interactions-two
      antiparallel N4H...O4 (5.19 kcal mol(-1)) and N3H...N3 (6.33 kcal mol(-1)) H
      bonds and a van der Waals (vdW) contact O2...O2 (0.32 kcal mol(-1)). The C.T base
      mispair is thermodynamically stable structure (DeltaG(int) = -1.54 kcal mol(-1) )
      and even slightly more stable than the A.T Watson-Crick DNA base pair
      (DeltaG(int) = -1.43 kcal mol(-1)) at the room temperature. It was shown that the
      C.T <-> C*.T* tautomerization via the double proton transfer (DPT) is assisted by
      the O2...O2 vdW contact along the entire range of the intrinsic reaction
      coordinate (IRC). The positive value of the Grunenberg's compliance constants
      (31.186, 30.265, and 22.166 A/mdyn for the C.T, C*.T*, and TS(C.T <-> C*.T*),
      respectively) proves that the O2...O2 vdW contact is a stabilizing interaction.
      Based on the sweeps of the H-bond energies, it was found that the
      N4H...O4/O4H...N4, and N3H...N3 H-bonds in the C.T and C*.T* base pairs are
      anticooperative and weaken each other, whereas the middle N3H...N3 H-bond and the
      O2...O2 vdW contact are cooperative and mutually reinforce each other. It was
      found that the tautomerization of the C.T base mispair through the DPT is
      concerted and asynchronous reaction that proceeds via the TS(C.T <-> C*.T*)
      stabilized by the loosened N4-H-O4 covalent bridge, N3H...N3 H-bond (9.67 kcal
      mol(-1) ) and O2...O2 vdW contact (0.41 kcal mol(-1) ). The nine key points,
      describing the evolution of the C.T <-> C*.T* tautomerization via the DPT, were
      detected and completely investigated along the IRC. The C*.T* mispair was
      revealed to be the dynamically unstable structure with a lifetime 2.13.* 10(-13)
      s. In this case, as for the A.T Watson-Crick DNA base pair, activates the
      mechanism of the quantum protection of the C.T DNA base mispair from its
      spontaneous mutagenic tautomerization through the DPT.

PMID- 23955923
TI  - Gene-by-diet interactions influence calcium absorption and bone density in mice.
AB  - Dietary calcium (Ca) intake is needed to attain peak bone mineral density (BMD).
      Habitual low Ca intake increases intestinal Ca absorption efficiency to protect
      bone mass, but the mechanism controlling, and the impact of genetics on, this
      adaptive response is not clear. We fed 11 genetically diverse inbred mouse lines
      a normal (0.5%) or low (0.25%) Ca diet from 4 to 12 weeks of age (n = 8 per diet
      per line) and studied the independent and interacting effects of diet and
      genetics on Ca and bone metabolism. Significant genetic variation was observed in
      all bone, renal, and intestinal phenotypes measured including Ca absorption.
      Also, adaptation of Ca absorption and bone parameters to low dietary Ca was
      significantly different among the lines. Ca absorption was positively correlated
      to femur BMD (r = 0.17, p = 0.02), and distal femur bone volume/tissue volume
      (BV/TV) (r = 0.34, p < 0.0001). Although Ca absorption was correlated to 1,25
      dihydroxyvitamin D (1,25(OH)2 D) (r = 0.35, p < 0.0001), the adaptation of Ca
      absorption to low Ca intake did not correlate to diet-induced adaptation of
      1,25(OH)2 D across the 11 lines. Several intestinal proteins have been proposed
      to mediate Ca absorption: claudins 2 and 12, voltage gated Ca channel v1.3
      (Cav1.3), plasma membrane Ca ATPase 1b (PMCA1b), transient receptor potential
      vanilloid member 6 (TRPV6), and calbindin D9k (CaBPD9k). Only the mRNA levels for
      TRPV6, CaBPD9k, and PMCA1b were related to Ca absorption (r = 0.42, 0.43, and
      0.21, respectively). However, a significant amount of the variation in Ca
      absorption is not explained by the current model and suggests that novel
      mechanisms remain to be determined. These observations lay the groundwork for
      discovery-focused initiatives to identify novel genetic factors controlling gene
      by-diet interactions affecting Ca/bone metabolism.

PMID- 23955924
TI  - Using the stress and adversity inventory as a teaching tool leads to significant
      learning gains in two courses on stress and health.
AB  - The ability to measure cumulative stress exposure is important for research and
      teaching in stress and health, but until recently, no structured system has
      existed for assessing exposure to stress over the lifespan. Here, we report the
      results of two experimental studies that examined the pedagogical efficacy of
      using an automated system for assessing life stress, called the Stress and
      Adversity Inventory (STRAIN), for teaching courses on stress and health. In Study
      1, a randomized, wait-list controlled experiment was conducted with 20 college
      students to test whether the STRAIN, coupled with a related lecture and
      discussion, promoted learning about stress and health. Results showed that this
      experiential lesson led to significant learning gains. To disentangle the effects
      of completing the STRAIN from participating in the lecture and discussion, we
      subsequently conducted Study 2 on 144 students using a 2 (STRAIN versus control
      activity) by 2 (STRAIN-specific lecture versus general stress lecture) repeated
      measures design. Although the STRAIN-specific lecture was sufficient for
      promoting learning, completing the STRAIN also generated significant learning
      gains when paired with only the general stress lecture. Together, these studies
      suggest that the STRAIN is an effective tool for promoting experiential learning
      and teaching students about stress and health.

PMID- 23955925
TI  - Focusing on value: this time is different.

PMID- 23955926
TI  - Insights into the molecular architecture of a peptide nanotube using FTIR and
      solid-state NMR spectroscopic measurements on an aligned sample.
AB  - Queuing up: Molecular orientation within macroscopically aligned nanotubes of the
      peptide AAAAAAK can be studied by solid-state NMR and IR spectroscopy. Line shape
      analysis of the NMR spectra indicates that the peptide N-H bonds are tilted 65-70
      degrees  relative to the nanotube long axis. Re-evaluation of earlier X-ray fiber
      diffraction data suggests that the peptide molecules are hydrogen-bonded in a
      helical arrangement along the nanotube axis.

PMID- 23955927
TI  - The potential of trehalose to replace insect hemolymph in artificial media for
      Trichogramma dendrolimi (Hymenoptera: Trichogrammatidae).
AB  - Insect additives have been shown to improve the value of artificial media for
      Trichogramma species, but at the same time maintain dependence on parallel
      cultures of host insects. In the present study, Trichogramma dendrolimi Matsumura
      was reared in vitro from egg to adult on artificial media with different contents
      of pupal hemolymph of Chinese oak silkmoth Antheraea pernyi (Guerin-Meneville)
      and with supplements of distilled water, or of trehalose dissolved in water or in
      Grace's insect medium. The results indicated insect hemolymph was the key
      component of artificial medium. Developmental parameters, including rates of
      parasitism, pupation, adult emergence and normal adults, and numbers of produced
      adults, were increased on media supplemented with trehalose even when the
      proportion of pupal hemolymph was reduced. Two artificial media, the first
      containing 30% hemolymph and 10% trehalose in water with 98.9% parasitism rate,
      77.7.0% pupation rate, 77.2% emergence rate, 80.0% normal adult rate and 333
      produced adults, and the second containing 25% hemolymph and 15% trehalose in
      Grace's insect medium with 97.8% parasitism rate, 91.0% pupation rate, 85.2%
      emergence rate, 76.1% normal adult rate and 757 produced adults, were believed to
      hold potential to mass produce T. dendrolimi. The use of trehalose to partially
      replace pupal hemolymph in artificial medium of this and other Trichogramma
      species may contribute to a significant reduction in their production cost and
      may as such help to evade problems related to short supplies of lepidopteran
      eggs, which currently constitute the main factitious host for the mass rearing of
      the parasitoids. 

PMID- 23955928
TI  - Violence against women and HIV risk behaviors in Kampala, Uganda: baseline
      findings from the SASA! Study.
AB  - This article presents baseline data from the SASA! (this is the Swahili for
      'now') Study, a cluster randomized trial of a community-mobilization intervention
      to prevent violence against women and HIV/AIDS in Kampala, Uganda. Logistic
      regression was used to explore associations between intimate partner violence
      (IPV) and sexual risk behaviors, among 1,206 ever-partnered men and women (18-49
      years). Twenty-seven percent of women reported past-year experience of physical
      and/or sexual IPV. Female experience and male perpetration of IPV were strongly
      associated with sexual risk behaviors. Findings confirm the importance of the
      SASA! intervention in this setting and endorse integrated strategies for IPV and
      HIV prevention.

PMID- 23955929
TI  - Changed and changing gender and family roles and domestic violence in African
      refugee background communities post-settlement in Perth, Australia.
AB  - In this study, domestic violence (DV) in five African refugee background
      communities post-settlement in Perth, Australia, is investigated-specifically,
      the interrelationship between experiences of DV, and changed and changing gender
      and family roles and responsibilities. The participatory qualitative design
      utilized in-depth interviews with 54 members of the Somalian, Sierra Leonean,
      Ethiopian, Liberian and Sudanese Communities, and focus groups with 24
      professionals who support them. Three key dimensions of this interrelationship
      are discussed: "male loss of the breadwinner role and status," "financial
      independence," and "mismatch between formal response and expectations." The
      importance of understanding experiences of DV within the context of cultural
      transition is highlighted here.

PMID- 23955930
TI  - Expanding resource theory and feminist-informed theory to explain intimate
      partner violence perpetration by court-ordered men.
AB  - This study tested resource and feminist-informed theories to explain physical,
      sexual, psychological, and stalking intimate partner violence (IPV) perpetrated
      by court-mandated men. Data were obtained from 340 men arrested for physical
      assault of a partner before their court-ordered treatment. Using path analysis,
      findings provided partial support for each model. Ineffective arguing and
      substance-use problems were moderators of resources and perpetration. Dominance
      mediated early exposures and perpetration in the feminist-informed model. In both
      models, predictors of stalking were different than those for other types of
      perpetration. Future studies should replicate this research and determine the
      utility of combining models.

PMID- 23955931
TI  - Partner violence and substance abuse are intertwined: women's perceptions of
      violence-substance connections.
AB  - Research shows that co-occurring partner violence and substance abuse are
      problems for many women. However, less is known about women's varied experiences
      with partner violence and substance abuse. This exploratory, qualitative study
      investigates these two issues among a sample of 15 women in substance abuse
      treatment who experienced partner violence. Overall, findings show participants'
      experience of violence-substance connections varied in important ways;
      complicating factors exacerbate both problems; and domestic violence services and
      substance abuse treatments should account for these variations and complications.
      We discuss directions for providers, researchers, and policymakers concerned with
      partner violence or substance abuse.

PMID- 23955933
TI  - Global efforts to engage men in preventing violence against women: an
      international survey.
AB  - This research note expands on the limited body of knowledge about men's
      engagement in preventing violence against women. One hundred and sixty-five
      individuals representing organizations from around the world participated in a
      brief online survey about their efforts to engage men in violence prevention.
      This study reveals a large and diverse global community working to engage men in
      preventing violence against women. The level of involvement is broad, from
      locally contained organizations to global collaborations. This study is a first
      step toward building a comparative knowledge base to inform program design and
      implementation. 

PMID- 23955932
TI  - College men's and women's respective perceptions of risk to perpetrate or
      experience sexual assault: the role of alcohol use and expectancies.
AB  - The present study examines alcohol use, expectancies (i.e., beliefs about the
      outcomes of alcohol consumption), and college men's (n = 127) and women's (n =
      191) respective perceptions of risk to perpetrate/experience sexual violence.
      Interactions between alcohol consumption and expectancies were examined. Alcohol
      expectancies regarding assertiveness increased women's perceived risk for sexual
      intercourse via alcohol/drugs. Among women reporting high alcohol use, global
      expectancies were positively associated with perceived risk for sexual
      intercourse via alcohol/drugs. Furthermore, among women reporting low alcohol
      use, expectancies regarding assertiveness were positively associated with
      perceived risk for coerced sexual contact. Implications are discussed. 

PMID- 23955935
TI  - Osteogenesis of adipose-derived stem cells on polycaprolactone-beta-tricalcium
      phosphate scaffold fabricated via selective laser sintering and surface coating
      with collagen type I.
AB  - The current study aimed to fabricate three-dimensional (3D) polycaprolactone
      (PCL), polycaprolactone and beta-tricalcium phosphate (PCL-TCP) scaffolds via a
      selective laser-sintering technique (SLS). Collagen type I was further coated
      onto PCL-TCP scaffolds to form PCL-TCP-COL scaffolds. The physical characters of
      these three scaffolds were analysed. The osteogenic potential of porcine adipose
      derived stem cells (pASCs) was compared among these three scaffolds in order to
      find an optimal scaffold for bone tissue engineering. The experimental results
      showed no significant differences in pore size and porosity among the three
      scaffolds; the porosity was ca. 75-77% and the pore size was ca. 300-500 um in
      all three. The compressive modulus was increased from 6.77 +/- 0.19 to 13.66 +/-
      0.19 MPa by adding 30% beta-TCP into a 70% PCL scaffold. No significant increase
      of mechanical strength was found by surface-coating with collagen type I.
      Hydrophilicity and swelling ratios showed statistical elevation (p < 0.05) after
      collagen type I was coated onto the PCL-TCP scaffolds. The in vitro study
      demonstrated that pASCs had the best osteogenic differentiation on PCL-TCP-COL
      group scaffolds, due to the highest ALP activity, osteocalcin mRNA expression and
      mineralization. A nude mice experiment showed better woven bone and vascular
      tissue formation in the PCL-TCP-COL group than in the PCL group. In conclusion,
      the study demonstrated the ability to fabricate 3D, porous PCL-TCP composite
      scaffolds (PCL:TCP = 70:30 by weight) via an in-house-built SLS technique. In
      addition, the osteogenic ability of pASCs was found to be enhanced by coating COL
      onto the PCL-TCP scaffolds, both in vitro and in vivo. Copyright (c) 2013 John
      Wiley & Sons, Ltd.

PMID- 23955936
TI  - A selective artificial enzyme inhibitor based on nanoparticle-enzyme interactions
      and molecular imprinting.
AB  - A novel and general strategy is developed to design selective artificial enzyme
      inhibitor based on nanoparticleenzyme inter actions and molecular imprinting. Due
      to the creation of specific binding cavities, the resulting artificial inhibitor
      has high inhibition efficiency for the target enzyme, and shows great target
      selectivity over other enzymes of similar function and proteins of compaable mole
      cular weight.

PMID- 23955937
TI  - Molecular identification of a pancreatic lipase-like gene involved in sex
      pheromone biosynthesis of Bombyx mori.
AB  - Cytoplasmic lipid droplet (LD) lipolysis is regulated by pheromone biosynthesis
      activating neuropeptide (PBAN) in Bombyx mori. To elucidate the molecular
      mechanism of cytoplasm LD lipolysis, the pancreatic lipase-like gene in B. mori
      pheromone glands (PGs), designated as B. mori pancreatic lipase-like gene
      (BmPLLG), was identified in this study. Spatial expression analysis revealed that
      BmPLLG is a ubiquitous gene present in all studied tissues, such as PGs, brain,
      epidermis, egg, midgut, flight muscle and fat body. Temporal expression analysis
      showed that the BmPLLG transcript begins to express 96 h before eclosion (-96 h),
      continues to increase, peaks in newly emerged females and steadily decreases
      after eclosion. Translational expression analysis of BmPLLG using a prepared
      antiserum demonstrated that BmPLLG was expressed in an age-dependent pattern at
      different development stages in B. mori. This finding was similar to the
      transcript expression pattern. Further RNA interference-mediated knockdown of
      BmPLLG significantly inhibited bombykol production. Overall, these results
      demonstrated that BmPLLG is involved in PBAN-induced sex pheromone biosynthesis
      and release. 

PMID- 23955938
TI  - Medullary thyroid cancer diagnosis: an appraisal.
AB  - Since its first description in 1951, a timely diagnosis of medullary thyroid
      carcinoma (MTC) may represent a diagnostic challenge in clinical practice.
      Several contributions have been addressed to the treatment and follow-up of MTC,
      but review articles focused on the diagnostic problems of this cancer in clinical
      practice are sparse. As a delayed diagnosis and an inadequate initial treatment
      may severely affect the prognosis of this thyroid malignancy, the appropriate use
      and the correct interpretation of the available diagnostic tools for MTC are of
      crucial importance. The purpose of the present article is to provide an easy-to
      use guide reviewing the main issues of MTC diagnosis: (1) basal serum calcitonin;
      (2) stimulated serum calcitonin; (3) additional serum markers for MTC; (4)
      ultrasound and other imaging techniques; (5) fine-needle aspiration (FNA)
      cytology; (6) calcitonin measurement on FNA washout; (7) rearranged during
      transfection (RET) mutations; and (8) scope of the problem.

PMID- 23955939
TI  - Integrated pest management concepts for red imported fire ants Solenopsis invicta
      (Hymenoptera: Formicidae).
AB  - Management of imported fire ant species has evolved since their accidental
      introduction into the United States and currently uses integrated pest management
      concepts to design, implement, and evaluate suppression programs. Although
      eradication is the management goal in certain isolated infestation sites,
      localized goals vary dramatically in larger infestations where reinvasion of
      treated areas is likely. These goals are influenced by regulatory policies,
      medical liabilities, ecological impact, and/or economic considerations. Tactics
      employed in fire ant management programs presented here include cultural and
      biological control options along with judicious use of site-specific insecticide
      products. In addition, program design considerations that include management
      goal(s), action level(s), ant form (monogyne or polygyne), presence of nontarget
      ant species, size of treatment area, seasonality, implementation cost, and
      environmental impact are also presented. Optimally, elegant IPM programs are
      target specific, threshold driven, environmentally friendly and cost-effective.

PMID- 23955940
TI  - Impact of the invasion of the imported fire ant.
AB  - The impact of the imported fire ant (IFA) is complex, in large part, because
      several very different species of "Fire Ants" have invaded and one of these has
      two forms, all of which are hard to separate by the public, as well as, some
      investigators not focused on the ant. Each of these different "IFA" species and
      forms differ in their impact. Further, these ants impact a number of "things"
      ranging from the environment and wildlife (plants and animals) as well as people,
      their environment and infrastructure. In addition, they can not only lead to
      death of living things (including people), but they can destroy many aspects of
      our environment and infrastructure at the cost of millions of dollars. But there
      are some beneficial aspects and some people can make many thousands of dollars
      due to their presence. This is an attempt to look at these issues.

PMID- 23955941
TI  - Effect of gland extracts on digging and residing preferences of red imported fire
      ant workers (Hymenoptera: Formicidae).
AB  - There is evidence that ant-derived chemical stimuli are involved in regulating
      the digging behavior in Solenopsis invicta Buren. However, the source gland(s)
      and chemistry of such stimuli have never been revealed. In this study, extracts
      of mandibular, Dufour's, postpharyngeal, and poison glands were evaluated for
      their effect on ant digging and residing preferences of S. invicta workers from
      three colonies. In the intracolonial bioassays, workers showed significant
      digging preferences to mandibular gland extracts in 2 of 3 colonies and
      significant residing preferences in 1 of 3 colonies; significant digging
      preferences to Dufour's gland extracts in 1 of 3 colonies and significant
      residing preferences in 2 of 3 colonies. No digging and residing preferences were
      found for postpharyngeal and poison gland extracts. In intercolonial bioassays,
      significant digging and residing preferences were found for mandibular gland
      extracts in 3 of 6 colony combinations. Significant digging preferences to
      Dufour's gland extracts were found in 4 of 6 colony combinations and significant
      residing preferences in all 6 colony combinations. For postpharyngeal gland
      extracts, significant digging preferences were found only in 1 of 6 colonial
      combinations and no significant residing preferences were found. For poison gland
      extracts, no significant digging preferences were found; significant residing
      preferences were found in 1 of 6 colony combinations. However, a significant
      residing deterrence (negative residing preference index) was found for 2 of 6
      colony combinations. Statistical analyses using data pooled from all colonies
      showed that mandibular and Dufour's gland extracts caused significant digging and
      residing preferences in both intracolonial and intercolonial bioassays but not
      postpharyngeal and poison gland extracts. By analyzing the data pooled from the
      same three colonies used for gland extract bioassays, it was found that, in no
      cases, workers showed significant digging and residing preferences to 2-ethyl-3,6
      dimethylpyrazine, an alarm pheromone component from mandibular gland.

PMID- 23955942
TI  - Arthropod prey of imported fire ants (Hymenoptera: Formicidae) in Mississippi
      sweetpotato fields.
AB  - The red imported fire ants, Solenopsis invicta (Buren), are generally considered
      pests. They have also been viewed as beneficial predators feeding on other insect
      pests of various agroecosystems. This study documents the foraging habits of fire
      ants in a sweetpotato field in Mississippi. Fire ant foraging trails connecting
      outside colonies to a sweetpotato field were exposed and foraging ants moving out
      of the field toward the direction of the colony were collected along with the
      solid food particles they were carrying. The food material was classified as
      arthropod or plant in origin. The arthropod particles were identified to orders.
      Fire ant foragers carried more arthropods than plant material. Coleoptera and
      Homoptera were the most abundant groups preyed upon. These insect orders contain
      various economically important pests of sweetpotato. Other major hexapod groups
      included the orders Hemiptera, Diptera and Collembola. The quantity of foraged
      material varied over the season. No damage to sweetpotato roots could be
      attributed to fire ant feeding. Imported fire ant foraging may reduce the number
      of insect pests in sweetpotato fields.

PMID- 23955943
TI  - Mosquito autogeny in Aedes caspius (Diptera: Culicidae): alterations of larval
      nourishments reservation upon bacterial infection.
AB  - The present study recorded mosquito autogeny for the first time amongst Aedes
      caspius species in the Eastern region of Saudi Arabia. Laboratory rearing showed
      an obligatory autogenous species of Ae. caspius since it foregoes blood feeding
      during its first ovarian cycle, even in the presence of the hosts (CD mouse), but
      produces its second egg batch only if ingested a blood meal. Both morphological
      and molecular identification confirmed that both autogenous and anautogenous
      strains belong to the same species of Ae. caspius. Data from biochemical analysis
      showed significant 2, 1.6, and 1.4 folds higher total carbohydrates, proteins,
      and lipids reserves respectively in the fourth larval instar of the autogenous
      strain compared to that of the anautogenous ones. In addition, exposing the
      fourth larval instars of autogenous strain to the infection stress by the
      mosquito larvicidal bacterium, Bacillus thuringiensis var kurstaki has
      significantly reduced total carbohydrates, proteins and lipids reserves by 29%,
      35%, and 46%, respectively, at 12 h postinfection compared to those of uninfected
      ones. These reductions in nourishment reserves were more pronounced at 24 h
      postinfection in the case of proteins and lipids, but not carbohydrates. These
      results may indicate that bacterial infection is a health stress that
      significantly reduced nourishments reservation, which may interrupt the success
      of adult autogeny. However, the impact of infection-induced decline in larval
      nourishments reservation on successful adult autogeny is still to be
      investigated.

PMID- 23955944
TI  - Characterization and transcriptional analyses of cDNAs encoding three trypsin-
      and chymotrypsin-like proteinases in Cry1Ab-susceptible and Cry1Ab-resistant
      strains of sugarcane borer, Diatraea saccharalis.
AB  - Diatraea saccharalis is a major corn borer pest. Midgut serine proteinases are
      essential for insect growth and development. Alteration of midgut proteinases is
      responsible for Bt resistance development in some species. To clone midgut
      trypsin and chymotrypsin cDNAs and to test if the Cry1Ab resistance in D.
      saccharalis is associated with changes in midgut proteinases, total midgut
      tryptic and chymotryptic activities, cDNA sequences, and gene expressions of
      three trypsin and three chymotrypsin genes were comparatively examined between
      Cry1Ab-susceptible (Cry1Ab-SS) and Cry1Ab-resistant (Cry1Ab-RR) strains. Full
      length cDNAs encoding three trypsin- and three chymotrypsin-like proteinases were
      sequenced from Cry1Ab-SS and Cry1Ab-RR larvae. These cDNAs code for active forms
      of midgut serine proteinases with all functional motifs, including signal
      peptide, conserved His-Asp-Ser for the catalytic triad, three pairs of cysteines
      for disulfide bridge configurations, and conserved substrate specificity
      determination residues. In general, cDNA and putative protein sequences are
      highly similar between Cry1Ab-SS and Cry1Ab-RR strains, except for a few
      nucleotide and predicted amino acid substitutions, whose function need to be
      further clarified. Total trypsin and chymotrypsin activities were also similar
      between Cry1Ab-SS and Cry1Ab-RR strains. Transcriptional levels of the trypsin
      and chymotrypsin genes had numerical difference between Cry1Ab-SS and Cry1Ab-RR
      strains, but the difference was not statistically significant. Data suggest that
      the development of Cry1Ab resistance in D. saccharalis was not significantly
      associated with these trypsins and chymotrypsins. Results clarified the role of
      six midgut proteinases and provided a foundation for continuing examination of
      potential involvement of other midgut proteinases in Bt resistance development
      and other important biochemical processes.

PMID- 23955945
TI  - Identification and characterization of a gene encoding a UBX domain-containing
      protein in the migratory locust, Locusta migratoria manilensis.
AB  - Ubiquitin regulatory X (UBX) domain-containing proteins are believed to function
      as cofactors for p97/CDC48, an adenosine triphosphatase shown to be involved in
      multiple cellular processes. In the present study, a full-length complementary
      DNA (cDNA) of UBX domain-containing gene, termed LmUBX1, was cloned from Locusta
      migratoria manilensis and characterized, using random amplification of cDNA ends
      polymerase chain reaction (RACE PCR), sequence analysis and quantitative real
      time PCR. LmUBX1, 1 600 bp in length, is predicted to encode a 446-amino acid
      protein with a predicted molecular weight of 51.18 kDa that contains a central
      PUB domain and a carboxy-terminal UBX domain. Homology analysis revealed that
      LmUBX1 has higher similarity to the known UBX domain-containing proteins from
      insects than from other species. Moreover, based on sequence characteristics and
      phylogenetic relationships, it is suggested that LmUBX1 can be classified into
      the UBXD1 subfamily. Expression analysis founded that LmUBX1 exhibited
      significant expression variations at different developmental stages and in
      different tissues, suggesting that the expression of LmUBX1 was highly regulated.
      Interestingly, its messenger RNA transcript was more abundant in ovary and testis
      than in other tissues examined, suggesting that it may have more important roles
      in the reproductive system. In addition, LmUBX1 was differentially expressed in
      gregarious and solitary locusts and was significantly up-regulated in third and
      fifth instars of gregarious locusts, implying that LmUBX1 was also likely
      involved in the phase polyphenisms in L. migratoria manilensis. To our knowledge,
      this is the first report of cloning of a full-length cDNA of UBX domain
      containing gene from L. migratoria manilensis.

PMID- 23955946
TI  - Resurgence of the cotton bollworm Helicoverpa armigera in northern Greece
      associated with insecticide resistance.
AB  - Helicoverpa armigera has been controlled effectively with chemical insecticides
      in the major cotton crop production areas of northern Greece for many years.
      However, a resurgence of the pest was observed in 2010, which significantly
      affected crop production. During a 4-year survey (2007-2010), we examined the
      insecticide resistance status of H. armigera populations from two major and
      representative cotton production areas in northern Greece against seven
      insecticides (chlorpyrifos, diazinon, methomyl, alpha-cypermethrin, cypermethrin,
      gamma-cyhalothrin and endosulfan). Full dose-response bioassays on third instar
      larvae were performed by topical application. Lethal doses at 50% were estimated
      by probit analysis and resistance factors (RF) were calculated, compared to a
      susceptible laboratory reference strain. Resistance levels were relatively
      moderate until 2009, with resistance ratios below 10-fold for organophosphates
      and carbamates and up to 16-fold for the pyrethroid alpha-cypermethrin. However,
      resistance rose to 46- and 81-fold for chlorpyrifos and alpha-cypermethrin,
      respectively in 2010, when the resurgence of the pest was observed. None of the
      known pyrethroid resistance mutations were found in the pyrethroid-resistant
      insects. The possible association between resistance and H. armigera resurgence
      in Greece is discussed.

PMID- 23955947
TI  - Impact of elevated CO2 and increased temperature on Japanese beetle herbivory.
AB  - To examine how the major elements of global change affect herbivory in
      agroecosystems, a multifactorial experiment was conducted where soybeans were
      grown at two levels of carbon dioxide and temperature, including those predicted
      for 2050, under otherwise normal field conditions. Japanese beetles (Popillia
      japonica Newman) were enclosed on foliage for 24 h, after which the beetle
      survivorship, total and per capita leaf consumption, and leaf protease inhibitor
      activity were measured. The direct effect of temperature on beetle consumption
      and survivorship also was measured under controlled environmental conditions. No
      differences in total foliage consumption were observed; however, beetles forced
      to feed at elevated temperature in the field demonstrated greater per capita
      consumption and reduced survivorship compared to beetles feeding at ambient
      temperature. Survivorship was also greater for beetles that consumed foliage
      grown under elevated CO2 , but there were no interactive effects of CO2 and
      temperature, and no differences in leaf chemistry were resolved. Leaf consumption
      by beetles increased strongly with increasing temperature up to ~37 degrees  C,
      above which increased mortality caused a precipitous decrease in consumption. An
      empirical model based on the temperature dependence of leaf consumption and
      flight suggests that the 3.5 degrees C increase in temperature predicted for 2050
      will increase the optimal feeding window for the Japanese beetle by 290%.
      Elevated temperature and CO2 operating independently have the potential to
      greatly increase foliage damage to soybean by chewing insects, such as Popillia
      japonica, potentially affecting crop yields.

PMID- 23955948
TI  - Comparing salinity tolerance in embryonic and larval development of two species
      of water strider, Aquarius paludum and Gerris latiabdominis (Hemiptera:
      Gerridae).
AB  - Water strider Aquarius paludum (Fabricius) is a cosmopolitan species colonizes
      mainly freshwater but occasionally brackish habitats throughout the Palearctic
      and Oriental regions. Water strider Gerris latiabdominis (Miyamoto) is a common
      species in Japan lives in temporary habitats as freshwater paddy fields. These
      two species often occur syntopically. We investigated differences in the
      developmental response to brackish water during embryonic and larval stages
      between the two species. Eggs were exposed to 0-1.8% NaCl solutions within 24 h
      of oviposition. Larvae of G. latiabdominis were exposed to salinities of 0, 0.5%,
      and 0.9% from the first instar until adult emergence. Limits of NaCl
      concentration for hatching were 1.3% and 1.0% for A. paludum and G.
      latiabdominis, respectively. The hatching rate of G. latiabdominis was lower than
      that of A. paludum at salinities >= 0.9%. The period of embryonic development of
      G. latiabdominis was more prolonged than that of A. paludum at a given salinity.
      Although the salinity tolerance of G. latiabdominis was lower than that of A.
      paludum, our results suggest G. latiabdominis has the physiological capacity to
      expand into brackish waters. High and low salinity tolerances of A. paludum and
      G. latiabdominis, respectively, reflect the relatively wide range of habitat
      salinities utilized by A. paludum and the relatively restricted habitats
      preferred by G. latiabdominis. The high salinity tolerance of A. paludum could be
      an important factor contributing to their cosmopolitan distribution because high
      tolerance to salinity means the possibility of them to be dispersed via ocean or
      sea to other continents and islands.

PMID- 23955949
TI  - Multiple generation effects of high temperature on the development and fecundity
      of Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) biotype B.
AB  - Insects are ectotherms and their ability to resist temperature stress is limited.
      The immediate effects of sub-lethal heat stress on insects are well documented,
      but longer-term effects of such stresses are rarely reported. In this study,
      survival, development and reproduction of the whitefly, Bemisia tabaci
      (Gennadius) (Hemiptera: Aleyrodidae) biotype B, were compared over five
      consecutive generations at 27, 31 and 35  degrees C and for one generation at 37 
      degrees C. Both temperature and generation significantly affected the fitness of
      the whitefly. These impacts were more dramatic with increasing generations and
      temperatures. Among the experimental temperatures, the most favorable for
      development and reproduction were 27  degrees C and 31  degrees C. At 27  degrees
      C, survival, development and fecundity were all stable over these five
      generations. At 31  degrees C, immature survival rate was the highest in the
      fifth generation, but female fecundities decreased in the fourth and fifth
      generations. At 35  degrees C, egg hatching rate, immature survival rate and
      female fecundity decreased significantly in the fourth and fifth generations. At
      37  degrees C, survival of B. tabaci was not adversely affected, but female
      fecundity at 37  degrees C was less than 10% of that at 27  degrees C or 31 
      degrees C. These results demonstrate that the lethal high temperature for B.
      tabaci is over 37  degrees C, and the whitefly population continued expanding in
      the five generations at 35  degrees C. The ability of B. tabaci biotype B to
      survive high temperature stress will play an important role in its population
      extension under global warming.

PMID- 23955950
TI  - Measurement of the time required for termites to pass each other in tunnels of
      different curvatures.
AB  - Subterranean termites construct complex tunnel networks for foraging. During
      travel in the tunnels, termites often encounter one another when passing in
      opposite directions. Such encounters are likely to affect the "movement
      efficiency," which is the time required for a termite to travel a certain
      distance in a tunnel. In this study, we explored how individual-individual
      encounters affect movement efficiency in tunnels by measuring the time (tau)
      taken by two termites to pass one another in tunnels of different curvatures.
      Artificial tunnels of 5 cm in length and variable widths (W) of 2, 3, or 4 mm
      were made. Tunnel distance (D) was 2, 3, 4, or 5 cm. When D had a higher value,
      curvature was lower. When W = 2, tau was significantly shorter in the tunnel with
      D = 5 than in tunnels of D = 2, 3, or 4, whereas tau was statistically the same
      for D = 2, 3 and 4. When W = 3, tau was shorter in the tunnel with D = 5 than for
      D = 3 and 4, while tau was longer in the tunnel with D = 2 than for D = 3 and 4.
      When W = 4, tau was longer in the tunnels with D = 2 and 3 than for D = 4 and 5.
      Based on these observations, 3 types of termite behavior were identified: biased
      walking, backward walking, and zigzag walking. We considered these results in
      relation to foraging efficiency.

PMID- 23955951
TI  - Processable Rylene Diimide Dyes up to 4 nm in Length: Synthesis and STM
      Visualization.
AB  - Long and planar: Facile syntheses of soluble hexarylene diimides (HDI) and
      octarylene diimides (ODI) are described. They are stable in both solution and the
      solid state and exhibit broad and intense NIR absorption. Scanning tunneling
      microscopy (STM) reveals that HDI, after deposition from solution, forms a unique
      herringbone bilayer or stable multilayers depending on the concentration. 

PMID- 23955952
TI  - Administration schedule and ototoxicity of amikacin in children with cancer.

PMID- 23955953
TI  - [Mediastinal parathyroid adenoma: a surgically treated case].
AB  - Sixteen percent of primary hyperparathyroidism is caused by ectopic parathyroid
      glands. These cases present diagnostic and therapeutic challenges. In this
      article we present the case of a patient underwent surgery for a mediastinal
      parathyroid adenoma causing symptomatic hypercalcaemia.

PMID- 23955954
TI  - [Medial sural artery perforator fasciocutaneous flap for the reconstruction of
      tongue and mouth base].
AB  - BACKGROUND: Despite the well-known high donor site morbidity of the radial forarm
      flap, it has still remained the first option for the reconstruction of the tongue
      and the floor of mouth. However, a desire for an alternative, thin
      fasciocutaneous flap has led to the use of the median sural artery perforator
      flap. METHODS: Three patients had reconstructive surgery used MSAP flaps, after
      radical tumor excision. RESULTS: The flap was based in all cases on a dominant
      perforator vessel. The size of the skin paddles ranged between 20-32 cm2, and the
      length of the vascular pedicle between 8.2-11 cm. The mean thickness of the flap
      was 6.5 mm. CONCLUSION: MSAP flap is an ideal solution for surgical
      reconstruction in the oral cavity.

PMID- 23955956
TI  - [Abstracts of the Conference of the Hungarian Association of Young Surgeons and
      Gastroenterologists, Balatonalmadi, April 12-14, 2013].

PMID- 23955961
TI  - Mental retardation-related protease, motopsin (prss12), binds to the BRICHOS
      domain of the integral membrane protein 2a.
AB  - Motopsin (prss12), a mosaic serine protease secreted by neuronal cells, is
      believed to be important for cognitive function, as the loss of its function
      causes severe nonsyndromic mental retardation. To understand the molecular role
      of motopsin, we identified the integral membrane protein 2a (Itm2a) as a motopsin
      interacting protein using a yeast two-hybrid system. A pull-down assay showed
      that the BRICHOS domain of Itm2a was essential for this interaction. Motopsin and
      Itm2a co-localized in COS cells and in cultured neurons when transiently
      expressed in these cells. Both proteins were co-immunoprecipitated from lysates
      of these transfected COS cells. Itm2a was strongly detected in a brain lysate
      prepared between postnatal day 0 and 10, during which period motopsin protein was
      also enriched in the brain. Immunohistochemistry detected Itm2a as patchy spots
      along endothelial cells of brain capillaries (which also expressed myosin II
      regulatory light chain [RLC]), and on glial fibrillary acidic protein (GFAP)
      positive processes in the developing cerebral cortex. The data raise the
      possibility that secreted motopsin interacts with endothelial cells in the
      developing brain. 

PMID- 23955962
TI  - The crude extract of Corni Fructus inhibits the migration and invasion of U-2 OS
      human osteosarcoma cells through the inhibition of matrix metalloproteinase-2/-9
      by MAPK signaling.
AB  - Osteosarcoma is the most common primary malignancy of the bone cancers. In the
      Chinese population, the crude extract of Corni Fructus (CECF) has been used as
      Traditional Chinese medicine to treat several different diseases for hundreds of
      years. In the present study, effects of CECF on inhibition of migration and
      invasion in U-2 OS human osteosarcoma cells were examined. CECF significantly
      inhibited migration and invasion of U-2 OS human osteosarcoma cells. We also
      found that CECF inhibited activities of matrix metalloproteinases-2 (MMP-2) and
      matrix metalloproteinases-9 (MMP-9). CECF decreased protein levels of FAK, PKC,
      SOS1, MKK7, MEKK3, GRB2, NF-kappaB p65, COX-2, HIF-1alpha, PI3K, Rho A, ROCK-1,
      IRE-1alpha, p-JNK1/2, p-ERK1/2, p-p38, Ras, p-PERK, MMP-2, MMP-9, and VEGF in U-2
      OS cells. Results of this study indicate that CECF may have potential as a novel
      anticancer agent for the treatment of osteosarcoma by inhibiting migration and
      invasion of cancer cells.

PMID- 23955963
TI  - Encounters with aphid predators or their residues impede searching and
      oviposition by the aphid parasitoid Aphidius ervi (Hymenoptera: Aphidiinae).
AB  - Intraguild predation (IGP) can be an important factor influencing the
      effectiveness of aphid natural enemies in biological control. In particular,
      aphid parasitoid foraging could be influenced by the presence of predators. This
      study investigated the effect of larvae of the predatory hoverfly Episyrphus
      balteatus DeGeer (Diptera: Syrphidae) and the multicolored Asian ladybird
      Harmonia axyridis Pallas (Coleoptera: Coccinellidae) on the foraging behavior of
      the aphid parasitoid, Aphidius ervi Haliday (Hymenoptera: Aphidiidae) in choice
      experiments using a leaf disc bioassay. Wasp response to chemical tracks left by
      those predator larvae was also tested. Parasitoid behavior was recorded using the
      Observer (Noldus Information Technology, version 5.0, Wageningen, the
      Netherlands). The experiments were conducted under controlled environmental
      conditions using leaves of the broad bean plant, Vicia faba L. (Fabaceae) with
      Myzus persicae Sulzer (Homoptera: Aphididae) as the host complex. A. ervi females
      avoided aphid patches when larvae of either predator were present. A similar
      avoidance response was shown by A. ervi to aphid patches with E. balteatus larval
      tracks, whereas no significant response was observed to tracks left by H.
      axyridis larvae. It was concluded that IG predator avoidance shown by the aphid
      parasitoid A. ervi may be a factor affecting their distribution among host
      patches.

PMID- 23955964
TI  - Self-/conspecific discrimination and superparasitism strategy in the ovicidal
      parasitoid Echthrodelphax fairchildii (Hymenoptera: Dryinidae).
AB  - Superparasitism in solitary parasitoids results in fatal competition between the
      immature parasitoids, and consequently only one individual can emerge. In the
      semisolitary ovicidal parasitoid Echthrodelphax fairchildii (Hymenoptera:
      Dryinidae), 2 adults can emerge under superparasitism with a short interval (<24
      h) between the first and second ovipositions. We determined the female
      parasitoid's behavioral responses under self- and conspecific superparasitism
      bouts with first-to-second oviposition intervals of <=2 h. The self- and
      conspecific superparasitizing frequencies increased up to an oviposition interval
      of 0.75 h, with the former remaining lower than the latter, particularly for
      oviposition intervals of <=0.25 h, suggesting the existence of self-/conspecific
      discrimination. The superparasitizing frequency plateaued for oviposition
      intervals of >=0.75 h, with no difference between self- and conspecific
      superparasitism. The ovicidal-probing frequency did not differ under self- and
      conspecific superparasitism, and was usually <20%. The females exhibited no
      preference for the oviposition side (i.e., ovipositing on the side with or
      without the first progeny) and almost always laid female eggs for any oviposition
      interval under self- and conspecific superparasitism. The sex ratio was not
      affected by the type of superparasitism, oviposition sides, or the occurrence of
      ovicidal probing. These observed results about the oviposition side, ovicidal
      probing, and sex ratios differed from the predictions obtained assuming that the
      females behave optimally. Possible reasons for the discrepancies are discussed:
      likely candidates include the high cost of selecting oviposition sides and
      ovicidal probing, and, for the sex ratio, the low frequency of encountering
      suitable hosts before superparasitism bouts.

PMID- 23955965
TI  - Delirium superimposed on dementia is associated with prolonged length of stay and
      poor outcomes in hospitalized older adults.
AB  - BACKGROUND: Current literature does not identify the significance of underlying
      cognitive impairment and delirium in older adults during and 30 days following
      acute care hospitalization. OBJECTIVE: Describe the incidence, risk factors, and
      outcomes associated with incident delirium superimposed on dementia. DESIGN: A 24
      month prospective cohort study. SETTING: Community hospital. PATIENTS: A total of
      139 older adults (>65 years) with dementia. METHODS: This prospective study
      followed patients daily during hospitalization and 1 month posthospital. Main
      measures included dementia (Modified Blessed Dementia Rating score, Informant
      Questionnaire on Cognitive Decline in the Elderly), daily mental status change,
      dementia stage/severity (Clinical Dementia Rating, Global Deterioration Scale),
      delirium (Confusion Assessment Method), and delirium severity (Delirium Rating
      Scale-Revised-98). All statistical analysis was performed using SAS 9.3, and
      significance was an alpha level of 0.05. Logistic regression, analysis of
      covariance, or linear regression was performed controlling for age, gender, and
      dementia stage. RESULTS: The overall incidence of new delirium was 32% (44/139).
      Those with delirium had a 25% short-term mortality rate, increased length of
      stay, and poorer function at discharge. At 1 month follow-up, subjects with
      delirium had greater functional decline. Males were more likely to develop
      delirium, and for every 1 unit increase in dementia severity (Global
      Deterioration Scale), subjects were 1.5 times more likely to develop delirium.
      CONCLUSIONS: Delirium prolongs hospitalization for persons with dementia. Thus,
      interventions to increase early detection of delirium have the potential to
      decrease the severity and duration of delirium and to prevent unnecessary
      suffering and costs from the complications of delirium and unnecessary
      readmissions to the hospital.

PMID- 23955967
TI  - Contemporary research findings on dentine remineralization.
AB  - Dentine remineralization is important for the treatment of dentine caries and the
      bonding durability of dentine and resin materials in clinical practice. Early
      studies of dentine remineralization were mostly based on the classical pathway of
      crystallization, which involves large-scale deposition of calcium phosphate
      crystals on collagen and is achieved in a liquid environment containing mineral
      ions. Results from these studies were unsatisfactory and not suitable for
      clinical application because they did not simulate the ordering of hydroxyapatite
      in the collagen fibres of natural teeth. As studies on collagen type I and non
      collagenous proteins have advanced, dentine biomimetic remineralization has
      become a popular research topic and has shifted to processes involving
      intrafibrillar remineralization, which is more similar to natural tooth
      formation. The objective of this review was to summarize current theory and
      research progress as it relates to dentine remineralization.

PMID- 23955966
TI  - Vertebral size, bone density, and strength in men and women matched for age and
      areal spine BMD.
AB  - To explore the possible mechanisms underlying sex-specific differences in
      skeletal fragility that may be obscured by two-dimensional areal bone mineral
      density (aBMD) measures, we compared quantitative computed tomography (QCT)-based
      vertebral bone measures among pairs of men and women from the Framingham Heart
      Study Multidetector Computed Tomography Study who were matched for age and spine
      aBMD. Measurements included vertebral body cross-sectional area (CSA, cm(2) ),
      trabecular volumetric BMD (Tb.vBMD, g/cm(3) ), integral volumetric BMD (Int.vBMD,
      g/cm(3) ), estimated vertebral compressive loading and strength (Newtons) at L3 ,
      the factor-of-risk (load-to-strength ratio), and vertebral fracture prevalence.
      We identified 981 male-female pairs (1:1 matching) matched on age (+/- 1 year)
      and QCT-derived aBMD of L3 (+/- 1%), with an average age of 51 years (range 34 to
      81 years). Matched for aBMD and age, men had 20% larger vertebral CSA, lower
      Int.vBMD (-8%) and Tb.vBMD (-9%), 10% greater vertebral compressive strength, 24%
      greater vertebral compressive loading, and 12% greater factor-of-risk than women
      (p < 0.0001 for all), as well as higher prevalence of vertebral fracture. After
      adjusting for height and weight, the differences in CSA and volumetric bone
      mineral density (vBMD) between men and women were attenuated but remained
      significant, whereas compressive strength was no longer different. In conclusion,
      vertebral size, morphology, and density differ significantly between men and
      women matched for age and spine aBMD, suggesting that men and women attain the
      same aBMD by different mechanisms. These results provide novel information
      regarding sex-specific differences in mechanisms that underlie vertebral
      fragility.

PMID- 23955968
TI  - [Anxiogenic and depressogenic side-effects of non-psychiatric drugs].
AB  - Although medications such as anticancer, antimicrobial, immunomodulatory,
      neurological or hormonal therapies may have a negative impact on mood, adequate
      attention was not paid until the withdrawal of rimonabant in 2008. In the present
      study the authors review full spectrum of currently available medications
      discussing anxiety and depression as possible adverse effects of treatment. A
      relatively high risk of depression should always be considered when
      pharmacotherapy applied, especially if current depressive episodes, positive
      family history, or neurotic personality traits increasing susceptibility to
      depressogenic effects. Prior to start of medical treatment, the potential
      effectiveness of the given drug should be precisely evaluated, and alternative
      medical and non-medical treatment options should also be carefully considered. In
      addition, monitoring patients during treatment for signs of depressive or anxious
      symptoms is necessary.

PMID- 23955969
TI  - [The role of endoscopic ultrasonography in the diagnosis of rectal cancers].
AB  - INTRODUCTION: The exact extent of rectal cancer and regional lymph node
      involvement are essential for providing the optimal treatment. AIM: The aim of
      the authors was to evaluate the diagnostic accuracy of endoscopic ultrasonography
      in routine clinical staging of rectal cancer. METHOD: Outcomes of endoscopic
      ultrasonography performed between 2006 and 2012 for rectal cancer staging were
      retrospectively analyzed. The correlation between the endoscopic and pathological
      stages was evaluated. RESULTS: In patients without neoadjuvant chemotherapy the
      sensitivity (75% and 73%) and specificity (74% and 80%) of endoscopic
      ultrasonography for differentiating T1 and T2 stages (respectively) were high,
      however, it was significantly decreased in differentiation of T3 stage (58%). A
      weak association was found in different N stages (45-62%). The diagnostic
      accuracy of endoscopic ultrasound was reduced significantly after the oncological
      treatment due to the overevaluation (27%) of the findings. After a relatively
      short learning curve (30 examinations) high correlation was detected between pT
      and uT stages. CONCLUSIONS: Endoscopic ultrasonography provides great help in
      staging early rectal cancers. Due to the lower sensitivity in patients receiving
      neoadjuvant therapy, it is not a useful tool after down-staging.

PMID- 23955970
TI  - [Colorectal carcinoma under the age of 50 years].
AB  - INTRODUCTION: Colorectal cancer is the second most common cause of cancer related
      death in Hungary. AIM: The authors examined retrospectively the ratio and the
      clinical course of patients under the age of 50 years operated by themselves
      between January, 2006 and May, 2012. METHOD: During this period of time 667
      patients underwent surgery for colorectal carcinoma and 44 (6.6%) were less than
      50 years old. 22.2% of the operations were performed for emergency reasons. The
      surgical technique, TNM stage, differentiation state and localization of the
      tumours were analyzed as well as the histological types with unfavourable
      prognosis. In order to analyse risk factors a questionnaire was sent to patients
      of young age group. RESULTS: The majority of patients, including those under 50
      years of age were diagnosed as having TNM stages III and IV. Only half of the
      patients returned the questionnaire. CONCLUSIONS: Due to a relatively low
      response rate, the importance of risk factors for colorectal carcinoma in
      patients under 50 years of age remains to be further investigated.

PMID- 23955971
TI  - [Comparative evaluation of left ventricular function by two-dimensional
      echocardiography and three-dimensional speckle-tracking echocardiography in
      noncompaction cardiomyopathy. Results from the MAGYAR-Path Study].
AB  - INTRODUCTION: Noncompaction cardiomyopathy develops due to the absence of
      myocardial compaction, and is associated with left ventricular dysfunction. AIM:
      The aim of the study was to evaluate comparatively left ventricular dysfunction
      in patients with noncompaction cardiomyopathy using two-dimensional
      echocardiography and three-dimensional speckle-tracking echocardiography. METHOD:
      The present study comprised of 7 patients with noncompaction cardiomyopathy
      (62.9+/-8.5 years, 3 males) and 10 age- and gender-matched healthy controls
      (60.7+/-7.7 years, 2 males). All patients were examined by two-dimensional
      echocardiography and three-dimensional speckle-tracking echocardiography for the
      evaluation of left ventricular function. RESULTS: Increased left ventricular end
      diastolic and end-systolic volumes and reduced left ventricular ejection fraction
      were detected in patients with noncompaction cardiomyopathy as compared to those
      measured in controls. All three-dimensional speckle-tracking echocardiography
      derived strain parameters of patients with noncompaction cardiomyopathy were
      found to be reduced as compared to the values of controls. Three-dimensional
      speckle-tracking echocardiography-derived rotational parameters showed movements
      of the apical and basal segments in the same direction suggesting 'rigid body
      rotation' in all noncompaction cardiomyopathy cases. CONCLUSIONS: Left
      ventricular function and contractility are severely reduced in patients with
      noncompaction cardiomyopathy. Absence of left ventricular twist could be
      demonstrated in a series of noncompaction cardiomyopathy patients.

PMID- 23955972
TI  - [The Physicians' Journal (1945-1949) and its editor: Dr. Gyorgy Kovacs (1900
      1965)].

PMID- 23955974
TI  - Male-killer dynamics in the tropical butterfly, Acraea encedana (Lepidoptera:
      Nymphalidae).
AB  - Sex ratio distortion in the tropical butterfly Acraea encedana is caused by
      infection with a male-killing bacterium of the genus Wolbachia. Previous research
      on this species has reported extreme female bias, high bacterial prevalences, and
      full sex role reversal. In this paper, we provide an assessment for the dynamics
      of the male-killer, based on a survey for sex ratios and Wolbachia prevalences
      among wild populations of A. encedana in Uganda. The study reveals that Wolbachia
      infection showed considerable variation over both spatial and temporal scales. 

PMID- 23955975
TI  - High-BMI at diagnosis is associated with inferior survival in patients with
      osteosarcoma: a report from the Children's Oncology Group.
AB  - BACKGROUND: Body mass index (BMI), at diagnosis has been associated with lower
      survival and increased toxicity in cancer patients. We analyzed the effect of BMI
      at diagnosis on therapy related toxicities and outcome in pediatric osteosarcoma
      patients treated on Children's Oncology Group (COG) trial INT0133. PROCEDURES:
      All patients enrolled on COG-INT0133 with height, weight and toxicity information
      were eligible. BMI was expressed as age and gender specific percentiles using
      height and weight at diagnosis. Patients were classified into high, normal and
      low BMI groups. Logistic regression models were used to analyze toxicities;
      Kaplan-Meier curves were created to assess event free (EFS) and overall survival
      (OAS). RESULTS: Seven hundred and ten patients met eligibility criteria. BMI
      distribution was: 447 normal BMI, 74 low BMI, and 189 high BMI. Renal toxicity
      was higher in the high BMI group (OR = 2.7, 95% CI 1.2-6.4, P = = 0.01) only
      during one of the courses of therapy. Compared to the normal BMI group, patients
      with high BMI had significantly worse OAS at 5 years compared to those with
      normal BMI, 69.7% versus 80.5% (HR = 1.6, 95% CI 1.1-2.2, P = 0.005) and a trend
      towards worse event-free survival at 3 years 66.2% versus 75.5% (HR = 1.3 95% CI
      0.9-1.8, P = 0.05). There was no difference in EFS or OAS in patients with low
      BMI compared to patients with normal BMI. CONCLUSIONS: High BMI at diagnosis is
      associated with worse OAS in patients with osteosarcoma. No clinically
      significant differences in toxicity were observed in the various BMI groups.

PMID- 23955976
TI  - Mechanisms for flowering plants to benefit arthropod natural enemies of insect
      pests: prospects for enhanced use in agriculture.
AB  - Reduction of noncrop habitats, intensive use of pesticides and high levels of
      disturbance associated with intensive crop production simplify the farming
      landscape and bring about a sharp decline of biodiversity. This, in turn, weakens
      the biological control ecosystem service provided by arthropod natural enemies.
      Strategic use of flowering plants to enhance plant biodiversity in a well
      targeted manner can provide natural enemies with food sources and shelter to
      improve biological control and reduce dependence on chemical pesticides. This
      article reviews the nutritional value of various types of plant-derived food for
      natural enemies, possible adverse effects on pest management, and the practical
      application of flowering plants in orchards, vegetables and field crops,
      agricultural systems where most research has taken place. Prospects for more
      effective use of flowering plants to maximize biological control of insect pests
      in agroecosystem are good but depend up on selection of optimal plant species
      based on information on the ecological mechanisms by which natural enemies are
      selectively favored over pest species. 

PMID- 23955977
TI  - Spontaneous adrenal haemorrhage in early pregnancy.
AB  - A 32-year-old primigravida presented at our emergency room at 6 weeks of
      gestation with acute severe right upper quadrant abdominal pain, radiating to the
      right flank. Vital signs were stable. Abdominal ultrasound showed a round
      inhomogeneous mass of 10 cm diameter behind the right kidney, suspected for
      adrenal haemorrhage. The patient was admitted for observation. An MRI showed some
      right-sided pleural effusion and a round mass in the adrenal region with no
      recognisable adrenal gland, therefore most likely originating from the right
      adrenal. After 10 days the patient was discharged with no change in size of the
      haematoma. MRI was carried out every 2 months which showed a decrease in size of
      the haematoma, with no other abnormalities. Based on stable MRI and the patient's
      preference, a vaginal delivery mode was chosen. At 37 weeks of gestation labour
      was induced, followed by an uncomplicated delivery.

PMID- 23955978
TI  - Transverse colon perforation due to carcinoma rectum: an unusual presentation
      against Laplace's law.
AB  - We present a case of distal large bowel obstruction, in the setting of a
      competent ileocaecal valve, the caecum is the most common site of perforation
      (for Laplace's law). We describe a case of obstruction at the rectum due to
      constricting carcinomatous growth, presenting with perforation of transverse
      colon (against Laplace's law). A 60-year-old women presented to the emergency
      department with acute abdominal pain. The pain was preceded by 3 days of
      intestinal obstruction. Clinically there was guarding and rigidity. Straight X
      ray of the abdomen revealed free gas under diaphragm. Surgical exploration
      revealed transverse colon perforation with carcinoma of rectum. Loop transverse
      colostomy was performed as the patient was very sick. The patient improved slowly
      in the intensive care unit. To conclude, even though the caecum is the most
      common site for perforation in case of distal obstruction, perforation of
      transverse colon can occur otherwise as a unique presentation.

PMID- 23955979
TI  - Management of post-treatment exacerbated temperomandibular disorder.
AB  - The patient returning to the clinic with a restricted mouth opening after dental
      treatment is common in dental practice. An extended, wide mouth opening during
      the dental treatment is known to exacerbate the underlying temperomandibular
      disorders (TMDs). Subclinical TMD is prevalent among a large number of people in
      the society. It is advisable in the interest of patients as well as the treating
      dentist for routine examination of temperomandibular joint and recording TMD
      history before initiating dental treatment. Adequate knowledge and skill of the
      dentist is required to identify the causative factors and initiate appropriate
      treatment. This case report explains the stabilising occlusal splint therapy to
      treat the restricted mouth opening in chronic centrally mediated myalgia flared
      up due to extended dental treatment.

PMID- 23955980
TI  - A complicated case of altered sensorium.
AB  - Tuberculosis and malaria are two common diseases afflicting the population of the
      Indian subcontinent. Both are associated with fatal neurological complications.
      Clinically, it may be difficult to differentiate between the two, except for that
      the focal neurological complications are more common with central nervous system
      (CNS) tuberculosis than with cerebral malaria. We report the case of a 48-year
      old woman who presented with a history of fever and altered sensorium of short
      duration. She was initially treated for falciparum malaria on the basis of
      positive peripheral smear and normal CT scan of the brain, but later on diagnosed
      to have CNS tuberculosis on the basis of persistence of symptoms, development of
      focal neurological symptoms and MRI of the brain showing multiple tuberculomas.
      She improved significantly with a course of antitubercular treatment (ATT) and
      systemic corticosteroids.

PMID- 23955981
TI  - Diffuse alveolar haemorrhage associated with aerosol propellant use.
AB  - Diffuse alveolar haemorrhage (DAH) is a clinical syndrome resulting from injury
      to the alveolar microcirculation, most commonly associated with not only
      autoimmune disorders or connective tissue disease, but also a variety of
      infections, neoplasms and toxins. We report here a case of an otherwise healthy
      young man with DAH attributable to an inhalation injury resulting from use of
      aerosol spray paint.

PMID- 23955982
TI  - Probable transmission of Yersinia enterocolitica from a pet dog with diarrhoea to
      a 1-year-old infant.
AB  - We report a highly probable case of transmission of a Yersinia enterocolitica
      from a pet puppy dog, adopted from a Spanish asylum, to a 1-year-old girl. After
      several weeks of diarrhoea, a PCR detecting enteropathogenic bacteria was
      performed on the faeces, revealing Y enterocolitica. Following cultures yielded a
      Y enterocolitica biotype 4, serotype O:3 in the faeces of the girl as well as
      puppy dog. Despite antibiotic treatment, symptoms and shedding of the organism in
      the faeces endured during a 2 month period.

PMID- 23955983
TI  - Acute perforated appendicitis in femoral hernia sac: CT imaging findings.

PMID- 23955984
TI  - Fatal upper gastrointestinal bleed arising from duodenal varices secondary to
      undiagnosed portal hypertension.
AB  - Duodenal varices are an unexpected source of upper gastrointestinal haemorrhage
      associated with high mortality. The prevalence of ectopic variceal bleeding
      accounts for 2-5% of all variceal bleeding; of this, only 17% occurs in the
      duodenum. Diagnosis is difficult, and insufficient evidence exists to demonstrate
      the best treatment option when haemorrhage occurs. We report the case of a 69
      year-old man with a history of chronic alcoholism who presented to the emergency
      department (ED) with nausea, vomiting and several episodes of haematochezia.
      Diagnostic workup in the ED included CT with multiplanar reconstruction, which
      revealed a network of large tortuous blood vessels running near the second
      portion of the duodenum between the inferior vena cava and portal vein. The
      patient was emergently treated with endoscopic therapy and clipping of the
      vessel. This failed, and he was subsequently taken to the operating room for
      suture ligation of the bleeding duodenal varices.

PMID- 23955985
TI  - Plantar fascia calcification a sequelae of corticosteroid injection in the
      treatment of recalcitrant plantar fasciitis.
AB  - We report the case of a 72-year-old woman suffering with severe plantar fasciitis
      who received a therapeutic corticosteroid injection. Two-and-a-half years after
      the injection she developed a small calcified lump under the skin which
      subsequently caused ulceration and infection. She went on to develop a diabetic
      foot infection requiring an extended course of intravenous antibiotics.

PMID- 23955986
TI  - Spontaneous rupture of splenic artery psuedoaneurysm into stomach: an uncommon
      presentation.

PMID- 23955987
TI  - Azathioprine-induced acute febrile neutrophilic dermatosis (Sweet's syndrome).

PMID- 23955988
TI  - Migration of a fractured ventriculoperitoneal shunt into the scrotum: a rare
      complication.

PMID- 23955989
TI  - Analysis of epothilone B-induced cell death in normal ovarian cells.
AB  - We have investigated the mode of cell death induced by a new microtubule
      stabilizing agent, epothilone B (EpoB, patupilone), and a clinically used
      medicine, paclitaxel (PTX), in normal ovarian cells. Using fluorescence
      microscopy, polyacrylamide gel electrophoresis preceding Western blot analysis,
      as well as spectrofluorimetric and colorimetric detection, we demonstrate that,
      compared to EpoB, PTX induced high time-dependent morphological and biochemical
      changes typical of apoptosis. Induction of apoptosis followed an early increase
      in p53 levels. Apoptosis reached its maximum at 24-48 h. At the same time, there
      was a significant increase in caspase-9 and -3 activity and PARP fragmentation,
      which suggests that an intrinsic path was involved. Apoptosis in MM14 cells was
      increased more by PTX than EpoB, and also induced more necrosis responsible for
      inflammation (1.4-fold) than EpoB.

PMID- 23955990
TI  - Developing functionalized dendrimer-like silica nanoparticles with hierarchical
      pores as advanced delivery nanocarriers.
AB  - Functionalized dendrimer-like hybrid silica nanoparticles with hierarchical pores
      are designed and synthesized. The unique structure, large surface area, and
      excellent biocompability render such materials attractive nanocarriers for the
      advanced delivery of various sized drugs and genes simultaneously. 

PMID- 23955991
TI  - Hypersensitivity reaction to high-dose methotrexate and successful rechallenge in
      a pediatric patient with osteosarcoma.
AB  - Hypersensitivity reactions to methotrexate are rare, but have been reported.
      Methotrexate has shown activity against many malignancies, and omission of
      methotrexate therapy may increase the risk of cancer-related death in some
      patients. Therefore, rechallenging patients with methotrexate following
      hypersensitivity may be beneficial. We report a case of a child with metastatic
      osteosarcoma who experienced a hypersensitivity reaction to high-dose
      methotrexate and was successfully rechallenged with methotrexate using a 6-hour
      infusion. Using this regimen, adequate peak methotrexate plasma concentrations
      were achieved and no further hypersensitivity reactions were noted.

PMID- 23955992
TI  - Risk factors and clinical indication of metastasis to lymph nodes posterior to
      right recurrent laryngeal nerve in papillary thyroid carcinoma: a single-center
      study in China.
AB  - BACKGROUND: Lymph nodes posterior to right recurrent laryngeal nerve (PRRLN) may
      be frequently overlooked during central compartment dissection (CCD) for
      papillary thyroid carcinoma (PTC). The purpose of this study was to investigate
      risk factors of lymph node PRRLN metastasis in right-sided PTC, thereby to
      identify the indications for lymph node PRRLN dissection. METHODS: We conducted a
      retrospective study of patients with right-sided PTC who underwent a
      thyroidectomy plus lymph node PRRLN dissection during ipsilateral CCD. RESULTS:
      Overall, 108 patients (26.7%) had lymph node PRRLN metastases, including 26
      (6.4%) who presented with solely lymph node PRRLN positivity. Factors of
      extrathyroidal extension, multifocality, larger tumor (>=1 cm), level VIa
      positivity (p < .0001 for each), and lateral compartments positivity (p = .0002)
      significantly predicted lymph node PRRLN metastasis in right-sided PTC.
      CONCLUSION: Lymph node PRRLN should be routinely explored during CCD because of
      the possibility of only involvement in PTC. Factors of tumors larger than 1 cm,
      multifocality, and extrathyroidal extension were independent predictors of lymph
      node PRRLN metastasis in right-sided PTC, and suggested the clinical indications
      of lymph node PRRLN dissection.

PMID- 23955993
TI  - Tyrosine metabolic enzymes from insects and mammals: a comparative perspective.
AB  - Differences in the metabolism of tyrosine between insects and mammals present an
      interesting example of molecular evolution. Both insects and mammals possess fine
      tuned systems of enzymes to meet their specific demands for tyrosine metabolites;
      however, more homologous enzymes involved in tyrosine metabolism have emerged in
      many insect species. Without knowledge of modern genomics, one might suppose that
      mammals, which are generally more complex than insects and require tyrosine as a
      precursor for important catecholamine neurotransmitters and for melanin, should
      possess more enzymes to control tyrosine metabolism. Therefore, the question of
      why insects actually possess more tyrosine metabolic enzymes is quite
      interesting. It has long been known that insects rely heavily on tyrosine
      metabolism for cuticle hardening and for innate immune responses, and these
      evolutionary constraints are likely the key answers to this question. In terms of
      melanogenesis, mammals also possess a high level of regulation; yet mammalian
      systems possess more mechanisms for detoxification whereas insects accelerate
      pathways like melanogenesis and therefore must bear increased oxidative pressure.
      Our research group has had the opportunity to characterize the structure and
      function of many key proteins involved in tyrosine metabolism from both insects
      and mammals. In this mini review we will give a brief overview of our research on
      tyrosine metabolic enzymes in the scope of an evolutionary perspective of mammals
      in comparison to insects. 

PMID- 23955994
TI  - Cloning, expression and chitin-binding activity of two peritrophin-like protein
      genes in the common cutworm, Spodoptera litura.
AB  - Insect midgut secretes a semi-permeable peritrophic membrane (PM), which plays
      important roles in protecting the midgut and helping with food digestion. The
      lepidopteran larvae produce type 1 PM, which is degraded when insects develop
      into the metamorphic stages. However, the underlying mechanism is unclear. In the
      present study, two peritrophin-like proteins (peritrophin-57 and 37) were
      identified from the midgut expression sequence tag library and transcriptome of
      the common cutworm, Spodoptera litura. The temporal and spatial expression
      patterns and responses to the induction of 20-hydroxyecdysone (20E) and
      starvation were examined by real-time quantitative polymerase chain reaction
      according to their common sequence region. The chitin-binding activity was also
      studied using a competitor, calcofluor. The open reading frames are 1 554 and 1
      020 bp, respectively. They shared four highly conserved peritrophin-A domains and
      were expressed only in the midgut rather than in the other tissues, including fat
      body, epidermis, Malpighian tube and hemolymph. Their transcriptional expression
      could only be detected at the larval stages rather than in eggs, prepupae, pupae
      and adults. The purified protein of peritrophin-37 bound to chitin in a dose
      dependent manner. These results indicate that the two proteins are peritrophins,
      the structural components of PM. In addition, the messenger RNA levels of the two
      peritrophins were significantly down-regulated by 20E injection, whereas
      feeding/starvation had no effect on the expression. These findings suggest that
      the increase of 20E titer may be an important factor which controls the
      degradation of PM during metamorphosis. 

PMID- 23955995
TI  - The beneficial effect of metformin on beta-cell function in non-obese Chinese
      subjects with newly diagnosed type 2 diabetes.
AB  - AIM: Studies with metformin suggest a favourable change in beta-cell function
      over sulphonylureas in the early course of obese type 2 diabetes mellitus (T2DM),
      but it remains unclear whether a similar effect is observed in non-obese
      individuals. Here we investigated the effects of metformin or glipizide
      gastrointestinal therapeutics system extended-release formulation (GITS) on beta
      cell function in non-obese patients with newly diagnosed T2DM. METHODS: A total
      of 160 newly diagnosed patients with fasting glucose 7.0-13.0 mmol/L and body
      mass index <30 kg/m(2) from five centres in China were randomized to metformin or
      glipizide GITS for 24 weeks. Early insulin secretion [the ratio of area under the
      curve (AUC) of insulin to glucose during 0-30 min (InsAUC30 /GluAUC30 )] and
      insulin sensitivity [Matsuda index (ISIM )] were assessed during the standard
      meal tolerance test before and after therapy. Plasma glucagon-like peptide-1(GLP
      1) and glucagon levels were also measured. RESULTS: Metformin improved InsAUC30
      /GluAUC30 significantly (from 8.1 +/- 0.6 pmol/mmol to 10.7 +/- 0.7 pmol/mmol, p
      < 0.05), comparable to results with glipizide GITS. In the metformin-treated lean
      (body mass index < 25 kg/m(2) ) subgroup, the increase in ISIM was not
      significant, but the improvement in InsAUC30 /GluAUC30 was of great magnitude.
      Increased GLP-1 responses during meal tolerance test and decreased fasting
      glucagon level were observed after metformin treatment. Correlation analysis
      showed that the improvement of InsAUC30 /GluAUC30 was associated with the changes
      in HbA1c (r = -0.374, p = 0.000), ISIM (r = 0.356, p = 0.001), and DeltaGLP-10-30
      (r = 0.225, p = 0.02). CONCLUSIONS: Metformin improved beta-cell function in non
      obese subjects with newly diagnosed T2DM, which was partly independent of the
      change in insulin sensitivity in these subjects. This study provides evidence
      based data to support metformin use in non-obese patients with T2DM as the first
      line agent, which can improve both insulin sensitivity and beta-cell function.

PMID- 23955996
TI  - Use of in situ atomic force microscopy to follow phase changes at crystal
      surfaces in real time.
AB  - AFM of cocrystals: Atomic force microscopy can be used to observe phase changes
      at crystal surfaces where the transformation is accompanied by a change in the
      spacing between layers of molecules. The conversion of a metastable polymorph of
      the caffeine-glutaric acid cocrystal into the thermodynamically stable form was
      analyzed continuously in situ using intermittent-contact-mode atomic force
      microscopy.

PMID- 23955997
TI  - The Bemisia tabaci species complex: additions from different parts of the world.
AB  - Bemisia tabaci is one of the most threatening pests in many crops. We sequenced
      part of the mitochondrial cytochrome oxidase I gene from fifty whitefly
      populations collected in Indonesia, Thailand, India and China. Nineteen unique
      sequences (haplotypes) of the cytochrome oxidase I were identified in these
      populations. They were combined with sequences available in databases, resulting
      in a total of 407 haplotypes and analyzed together with nine outgroup accessions.
      A phylogenetic tree was calculated using the maximum likelihood method. The tree
      showed that all groups that were found in previous studies were also present in
      our study. Additionally, seven new groups were identified based on the new
      haplotypes. Most B. tabaci haplotypes grouped based on their geographical origin.
      Two groups were found to have a worldwide distribution. Our results indicate that
      our knowledge on the species complex around B. tabaci is still far from complete.

PMID- 23956000
TI  - Implications for osmorespiratory compromise by anatomical remodeling in the gills
      of Arapaima gigas.
AB  - The gill structure of the Amazonian fish Arapaima gigas, an obligatory air
      breather, was investigated during its transition from water breathing to the
      obligatory air breathing modes of respiration. The gill structure of A. gigas
      larvae is similar to that of most teleost fish; however, the morphology of the
      gills changes as the fish grow. The main morphological changes in the gill
      structure of a growing fish include the following: (1) intense cell proliferation
      in the filaments and lamellae, resulting in increasing epithelial thickness and
      decreasing interlamellar distance; (2) pillar cell system atrophy, which reduces
      the blood circulation through the lamellae; (3) the generation of long
      cytoplasmic processes from the epithelial cells into the intercellular space,
      resulting in continuous and sinuous paracellular channels between the epithelial
      cells of the filament and lamella that may be involved in gas, ion, and nutrient
      transport to epithelial cells; and (4) intense mitochondria-rich cell (MRC)
      proliferation in the lamellar epithelium. All of these morphological changes in
      the gills contribute to a low increase of the respiratory surface area for gas
      exchange and an increase in the water-blood diffusion distance increasing their
      dependence on air-breathing as fish developed. The increased proliferation of
      MRCs may contribute to increased ion uptake, which favors the regulation of ion
      content and pH equilibrium.

PMID- 23956001
TI  - General one-pot reductive gem-bis-alkylation of tertiary lactams/amides: rapid
      construction of 1-azaspirocycles and formal total synthesis of (+/-)
      cephalotaxine.
AB  - Amides are a class of highly stable and readily available compounds. The amide
      functional group constitutes a class of powerful directing/activating and
      protecting group for C-C bond formation. Tertiary tert-alkylamine, including 1
      azaspirocycle is a key structural feature found in many bioactive natural
      products and pharmaceuticals. The transformation of amides into tert-alkylamines
      generally requires several steps. In this paper, we report the full details of
      the first general method for the direct transformation of tertiary lactams/amides
      into tert-alkylamines. The method is based on in situ activation of amide with
      triflic anhydride/2,6-di-tert-butyl-4-methylpyridine (DTBMP), followed by
      successive addition of two organometallic reagents of the same or different kinds
      to form two C-C bonds. Both alkyl and functionalized organometallic reagents and
      enolates can be used as the nucleophiles. The method displayed excellent 1,2- and
      good 1,3-asymmetric induction. Construction of 1-azaspirocycles from lactams
      required only two steps or even one-step by direct spiroannelation of lactams.
      The power of the method was demonstrated by a concise formal total synthesis of
      racemic cephalotaxine.

PMID- 23956002
TI  - Zoonotic infections in pediatric patients with acute leukemia.
AB  - Few studies have described the impact of zoonotic diseases in children with
      leukemia. This study aimed to describe the frequency of and associated
      demographic factors for zoonotic diseases in pediatric acute leukemia patients.
      Descriptive and comparative statistics relative to age, sex, and patient region
      were performed on an assembled 11-year retrospective cohort of acute leukemia
      patients. Of 10,197 patients, 88 patients (0.86%) were found to have a zoonotic
      infection. Gastrointestinal diseases were the most commonly (86.4%) identified
      zoonotic illnesses. Although rare, zoonotic diseases do occur in children with
      leukemia and frequency varies by age, region, and gender.

PMID- 23956003
TI  - Subcellular elevation of cytosolic free calcium is required for osteoclast
      migration.
AB  - Osteoclasts are multinucleated cells responsible for the resorption of bone and
      other mineralized tissues during development, physiological remodeling, and
      pathological bone loss. Osteoclasts have the ability to resorb substrate while
      concurrently migrating. However, the subcellular processes underlying migration
      are not well understood. It has been proposed that, in other cell types,
      cytosolic free Ca(2+) concentration ([Ca(2+) ]i ) regulates cell protrusion as
      well as retraction. Integration of these distinct events would require precise
      spatiotemporal patterning of subcellular Ca(2+) . The large size of osteoclasts
      offers a unique opportunity to monitor patterns of Ca(2+) during cell migration.
      We used ratiometric imaging to map [Ca(2+) ]i within rat and mouse osteoclasts.
      Migration was characterized by lamellipodial outgrowth at the leading edge, along
      with intermittent retraction of the uropod. Migrating osteoclasts displayed
      elevation of [Ca(2+) ]i in the uropod, that began prior to retraction.
      Dissipation of this [Ca(2+) ]i gradient by loading osteoclasts with the Ca(2+)
      chelator BAPTA abolished uropod retraction, on both glass and mineralized
      substrates. In contrast, elevation of [Ca(2+) ]i using ionomycin initiated prompt
      uropod retraction. To investigate downstream effectors, we treated cells with
      calpain inhibitor-1, which impaired uropod retraction. In contrast, lamellipodial
      outgrowth at the leading edge of osteoclasts was unaffected by any of these
      interventions, indicating that the signals regulating outgrowth are distinct from
      those triggering retraction. The large size of mature, multinucleated osteoclasts
      allowed us to discern a novel spatiotemporal pattern of Ca(2+) involved in cell
      migration. Whereas localized elevation of Ca(2+) is necessary for uropod
      retraction, lamellipod outgrowth is independent of Ca(2+) -a heretofore
      unrecognized degree of specificity underlying the regulation of osteoclast
      migration.

PMID- 23956004
TI  - Multidimensional needs of caregivers for patients with cancer.
AB  - This pilot study describes the multidimensional (physical, psychological, social,
      and spiritual) needs of caregivers of cancer survivors. A regional comprehensive
      cancer center and nine community-based rural and urban cancer clinics in New
      Hampshire assembled a convenience sample. Patients with cancer completed an
      online survey, the cancer survivor Web-based needs assessment survey (CS-WEBS),
      to identify needs and desire for intervention. Patients then identified a
      caregiver who was recruited to complete a caregiver version of the CS-WEBS.
      Caregivers reported challenges within all four domains of the survivorship model.
      The highest reported physical symptoms were fatigue, insomnia, and weight gain.
      Social symptoms included financial issues. Although visiting nurse services were
      the most commonly used resource, many caregivers used no supportive services. The
      most common caregiver task was listening and talking. Caregivers frequently
      experienced fatigue, anxiety, and insomnia. Exploring effective ways to alleviate
      their symptom burden should be a priority. Local and national attention should be
      directed toward easing the financial burden of caring for a patient with cancer. 

PMID- 23956005
TI  - Flexible and weaveable capacitor wire based on a carbon nanocomposite fiber.
AB  - A flexible and weaveable electric double-layer capacitor wire is developed by
      twisting two aligned carbon nanotube/ordered mesoporous carbon composite fibers
      with remarkable mechanical and electronic properties as electrodes. This
      capacitor wire exhibits high specific capacitance and long life stability.
      Compared with the conventional planar structure, the capacitor wire is also
      lightweight and can be integrated into various textile structures that are
      particularly promising for portable and wearable electronic devices. 

PMID- 23956006
TI  - Overexpression of vasostatin-1 protects hypoxia/reoxygenation injuries in
      cardiomyocytes-endothelial cells transwell co-culture system.
AB  - Vasostatin-1 (VS-1) plays important roles in myocardial ischemia/reperfusion
      injury. We have explored the protective effects of VS-1 on cardiomyocytes using
      cardiomyocyte-endothelial cells Transwell Co-culture System. Cardiomyocytes and
      rat aortic endothelial cells (RAECs) were prepared from ventricles and thoraco
      abdominal aorta of Sprague-Dawley rats. The experiment used cardiomyocytes alone
      culture group (C) and cardiomyocytes-RAECs co-culture group (T), each with three
      subgroups: C-Ad-Null, C-Ad-VS-1, C-Hb (Ad-VS-1 + NO scavenger Hb), or T-Ad-Null,
      T-Ad-VS-1 transfection, T-Hb. After 48 h incubation, all groups were treated with
      hypoxia for 60 min and then reoxygenated for 120 min. We also investigated
      endothelial cells-mediated cardiomyocytes protection. RAECs were treated with
      hypoxia for 30 min and reoxygenated with normal cardiomyocytes for 120 min. The
      cardiomyocytes apoptosis rate, aspartate aminotransferase (AST) and creatine
      kinase isozyme MB (CK-MB) were recorded. As expected, cardiomyocytes apoptosis,
      AST and CK-MB were significantly increased in the T-Ad-Null group than in the C
      Ad-Null group. VS transfection significantly reduced these levels. However,
      apoptosis, AST and CK-MB levels were increased again after Hb treatment,
      returning to the similar level of the C-Ad-null group in the C-Hb group, but
      still significantly lower in the T-Hb group compared with the T-Ad-null group.
      RAEC injury caused cardiomyocyte injury, and VS-1 transfection of the RAEC
      decreased apoptosis and the levels of AST and CK-MB. The findings suggest that VS
      1 exerts protective effects on the cardiomyocytes directly or indirectly by
      cardiomyocyte-endothelial cells interaction. 

PMID- 23956007
TI  - Oral hypoglycaemic agents and the development of non-fatal cardiovascular events
      in patients with type 2 diabetes mellitus.
AB  - AIMS: This study aimed to assess the risk of non-fatal cardiovascular events
      among patients with type 2 diabetes mellitus (T2DM) who are taking metformin,
      glimepiride or glyburide. MATERIALS AND METHODS: Using the National Health
      Insurance Research database in Taiwan, this retrospective cohort study identified
      1159 patients with newly diagnosed T2DM from 1998 to 2007, 30 years and older and
      without a history of cardiovascular disease at baseline. Patients with cancer,
      liver cirrhosis or chronic kidney disease were excluded. On the basis of
      prescription, patients were grouped into three medication subcohorts: metformin
      (N = 595), glimepiride (N = 234) or glyburide (N = 330) monotherapy for 100% of
      the follow-up period without any oral anti-diabetic agents added or changed, by
      the end of 2009. Incidence and hazard ratios of non-fatal cardiovascular events
      including coronary artery disease, peripheral artery disease, stroke and heart
      failure among these three subcohorts were compared. RESULTS: The overall
      incidence of non-fatal cardiovascular events was the highest for patients taking
      glyburide (169.1 per 1000 person-years), followed by for those taking glimepiride
      and metformin (95.2 and 49.1 per 1000 person-years, respectively). Compared with
      the adjusted hazard ratio for patients taking glyburide, the adjusted hazard
      ratio for those taking glimepiride was 0.52 (95% CI 0.40-0.69) and for those
      taking metformin was 0.31 (95% CI 0.24-0.40). CONCLUSIONS: T2DM patients taking
      metformin and glimepiride are at lower risk of non-fatal cardiovascular events
      than those taking glyburide.

PMID- 23956008
TI  - The apical plasma membrane of chitin-synthesising epithelia.
AB  - Chitin is the second most abundant polysaccharide on earth. It is produced at the
      apical side of epidermal, tracheal, fore- and hindgut epithelial cells in insects
      as a central component of the protective and supporting extracellular cuticle.
      Chitin is also an important constituent of the midgut peritrophic matrix that
      encases the food supporting its digestion and protects the epithelium against
      invasion by possibly ingested pathogens. The enzyme producing chitin is a
      glycosyltransferase that resides in the apical plasma membrane forming a pore to
      extrude the chains of chitin into the extracellular space. The apical plasma
      membrane is not only a platform for chitin synthases but, probably through its
      shape and equipment with distinct factors, also plays an important role in
      orienting and organising chitin fibres. Here, I review findings on the cellular
      and molecular constitution of the apical plasma membrane of chitin producing
      epithelia mainly focussing on work done in the fruit fly Drosophila melanogaster.

PMID- 23956010
TI  - Composition and distribution of ground-dwelling beetles among oak fragments and
      surrounding pine plantations in a temperate forest of North China.
AB  - In this study, we compared ground-dwelling beetle assemblages (Coleoptera) from a
      range of different oak fragments and surrounding conifer plantations to evaluate
      effects of forest size and surrounding matrix habitat in a temperate forest of
      north China. During 2000, beetles were sampled via pitfall traps within two large
      oak fragments (ca. 2.0-4.0 ha), two small oak fragments (ca. 0.2-0.4 ha) and two
      surrounding matrices dominated by pine plantations (>4 ha) in two sites of
      different aspects. Overall, no significantly negative effects from forest patch
      size and the surrounding matrix habitat were detected in total species number and
      abundance of ground-dwelling beetles. However, compared with small oak patches or
      pine plantations, more species were associated with an affinity for at least one
      large oak patch of the two aspects. Multivariate regression trees showed that the
      habitat type better determined the beetle assemblage structure than patch size
      and aspect, indicating a strong impact of the surrounding matrix. Linear mixed
      models indicated that species richness and abundance of all ground-dwelling
      beetles or beetle families showed different responses to the selected
      environmental variables. Our results suggest that more disturbed sites are
      significantly poorer in oak forest specialists, which are usually more abundant
      in large oak fragments and decrease in abundance or disappear in small fragments
      and surrounding matrix habitats. Thus, it is necessary to preserve a minimum size
      of forest patch to create conditions characteristic for forest interior, rather
      than the more difficult task of increasing habitat connectivity. 

PMID- 23956009
TI  - Optical coherence tomography imaging during thyroid and parathyroid surgery: a
      novel system of tissue identification and differentiation to obviate tissue
      resection and frozen section.
AB  - BACKGROUND: Optical coherence tomography (OCT) allows tissue histologic-like
      evaluation, but without tissue fixation or staining. We investigated OCT images
      from tissues obtained at thyroid and parathyroid surgeries to provide a
      preliminary assessment as to whether these images contain sufficient information
      for recognition and differentiation of normal neck tissues. METHODS: Normal
      tissues were obtained from patients undergoing surgical treatment. Two new
      generation OCT systems, including optical frequency domain imaging (OFDI) and
      MUOCT, were compared to representative hematoxylin-eosin histology. RESULTS:
      Thyroid, fat, muscle, lymph nodes, and parathyroid tissues were evaluated.
      Histologic-like microscopic characteristics sufficient for tissue type
      identification was realized using both systems for all tissue types examined.
      CONCLUSION: This pilot study demonstrated that new-generation OCT systems are
      capable of recognizing and differentiating neck tissues encountered during
      thyroid and parathyroid surgeries. Further advances in OCT miniaturization and
      development of sterile intraoperative probe formats may allow OCT to offer an
      intraoperative "optical biopsy" without fixation, staining, or tissue resection.

PMID- 23956011
TI  - Genome-wide analysis of Nilaparvata lugens nymphal responses to high-density and
      low-quality rice hosts.
AB  - The brown planthopper (BPH) Nilaparvata lugens is an economically important pest
      on rice plants. In this study, the higher population density and yellow-ripe
      stage of rice plants were used to construct adverse survival conditions (ASC)
      against BPH nymphs. Simultaneously, the low population density and tillering
      stage of rice plants were used to establish a suitable survival condition (SSC)
      as a control. Solexa/Illumina sequencing was used to identify genes of BPH nymphs
      responding to ASC. Significantly longer duration development of BPH nymphs and
      significantly lower brachypterous ratio of BPH adults were observed by ASC
      compared with SSC. A total of 2 544 differentially expressed genes (DEGs) were
      obtained and analyzed by BLASTx, Gene Ontology and KEGG Orthology. Gene ontology
      analysis revealed that the DEGs were mainly involved in categories of cell, cell
      part, cellular process, binding, catalytic, organelle and metabolic processes. 1
      138 DEGs having enzyme commission numbers were assigned to different metabolic
      pathways. The largest clusters were neurodegenerative diseases (137, 12.0%),
      followed by carbohydrate metabolism (113, 9.9%), amino acid metabolism (94,
      8.3%), nucleotide metabolism (76, 6.7%), energy metabolism (64, 5.6%),
      translation (60, 5.3%), lipid metabolism (58, 5.1%), and folding, sorting and
      degradation (52, 4.6%). Expressing profile of 11 DEGs during eight nymphal
      developmental stages of BPH were analyzed by quantitative real-time polymerase
      chain reaction. The 11 genes exhibited differential expression between ASC and
      SSC during at least one developmental stage. The DEGs identified in this study
      provide molecular proof of how BPH reconfigures its gene expression profile to
      adapt to overcrowding and low-quality hosts. 

PMID- 23956012
TI  - Selectively N-methylated soluble IAPP mimics as potent IAPP receptor agonists and
      nanomolar inhibitors of cytotoxic self-assembly of both IAPP and Abeta40.

PMID- 23956013
TI  - Comparative effects of insecticides with different mechanisms of action on
      Chrysoperla externa (Neuroptera: Chrysopidae): lethal, sublethal and dose
      response effects.
AB  - The comprehensive knowledge that the delayed systemic and reproduction side
      effects can be even more deleterious than acute toxicity, has caused a shift in
      focus toward sublethal effects assessment on physiology and behavior of
      beneficial insects. In this study, we assessed the risks posed by some
      insecticides with different mode of action through lethal and delayed systemic
      sublethal effects on the pupation, adult emergence, and reproduction of the
      chrysopid Chrysoperla externa (Hagen, 1861; Neuroptera: Chrysopidae), an
      important predator in pest biological control. The maximum field recommended dose
      (MFRD) and twice (2*MFRD) for chlorantraniliprole, tebufenozide, and pyriproxyfen
      were harmless to C. externa. In contrast, all the tested chitin synthesis
      inhibitors (CSIs) were highly detrimental to the predator, despite of their lack
      of acute lethal toxicity. Therefore, the safety assumed by using IGRs toward
      beneficial insects is not valid for chrysopids. Dose-response data showed that
      although all CSIs have a similar mechanism of action, the relative extent of
      toxicity may differ (novaluron > lufenuron > teflubenzuron). For CSIs, the
      delayed systemic effects became obvious at adult emergence, where the predicted
      no observable effect dose (NOED) was 1/2 048 of the MFRD for novaluron (0.085
      ng/insect), and 1/256 of the MFRD for both lufenuron (0.25 ng/insect) and
      teflubenzuron (0.6 ng/insect). Finally, this work emphasized the significance of
      performing toxicity risk assessments with an adequate posttreatment period to
      avoid underestimating the toxicities of insecticides, as the acute lethal
      toxicity assays may not provide accurate information regarding the long-range
      effects of hazardous compounds. 

PMID- 23956014
TI  - Bioengineered tunable memristor based on protein nanocage.
AB  - Bioengineered protein-based nanodevices with tunable and reproducible memristive
      performance are fabricated by combining the unique high loading capacity of
      Archaeoglobus fulgidus ferritin with OWL-generated nanogaps. By tuning the iron
      amount inside ferritin, the ON/OFF ratio of conductance switching can be
      modulated accordingly. Higher molecular loading exhibits better memristive
      performance owing to the higher electrochemical activity of the ferric complex
      core. 

PMID- 23956015
TI  - Estimating the information gap between emergency department records of community
      medication compared to on-line access to the community-based pharmacy records.
AB  - OBJECTIVE: Errors in community medication histories increase the risk of adverse
      events. The objectives of this study were to estimate the extent to which access
      to community-based pharmacy records provided more information about prescription
      drug use than conventional medication histories. MATERIALS AND METHODS: A
      prospective cohort of patients with public drug insurance who visited the
      emergency departments (ED) in two teaching hospitals in Montreal, Quebec was
      recruited. Drug lists recorded in the patients' ED charts were compared with
      pharmacy records of dispensed medications retrieved from the public drug insurer.
      Patient and drug-related predictors of discrepancies were estimated using general
      estimating equation multivariate logistic regression. RESULTS: 613 patients
      participated in the study (mean age 63.1 years, 59.2% women). Pharmacy records
      identified 41.5% more prescribed medications than were noted in the ED chart.
      Concordance was highest for anticoagulants, cardiovascular drugs and diuretics.
      Omissions in the ED chart were more common for drugs that may be taken
      episodically. Patients with more than 12 medications (OR 2.92, 95% CI 1.71 to
      4.97) and more than one pharmacy (OR 3.85, 95% CI 1.80 to 6.59) were more likely
      to have omissions in the ED chart. DISCUSSION: The development of health
      information exchanges could improve the efficiency and accuracy of information
      about community medication histories if they enable automated access to dispensed
      medication records from community pharmacies, particularly for the most
      vulnerable populations with multiple morbidities. CONCLUSIONS: Pharmacy records
      identified a substantial number of medications that were not in the ED chart.
      There is potential for greater safety and efficiency with automated access to
      pharmacy records.

PMID- 23956016
TI  - Use of computerized algorithm to identify individuals in need of testing for
      celiac disease.
AB  - BACKGROUND AND AIM: Celiac disease (CD) is a lifelong immune-mediated disease
      with excess mortality. Early diagnosis is important to minimize disease symptoms,
      complications, and consumption of healthcare resources. Most patients remain
      undiagnosed. We developed two electronic medical record (EMR)-based algorithms to
      identify patients at high risk of CD and in need of CD screening. METHODS: (I)
      Using natural language processing (NLP), we searched EMRs for 16 free text (and
      related) terms in 216 CD patients and 280 controls. (II) EMRs were also searched
      for ICD9 (International Classification of Disease) codes suggesting an increased
      risk of CD in 202 patients with CD and 524 controls. For each approach, we
      determined the optimal number of hits to be assigned as CD cases. To assess
      performance of these algorithms, sensitivity and specificity were calculated.
      RESULTS: Using two hits as the cut-off, the NLP algorithm identified 72.9% of all
      celiac patients (sensitivity), and ruled out CD in 89.9% of the controls
      (specificity). In a representative US population of individuals without a prior
      celiac diagnosis (assuming that 0.6% had undiagnosed CD), this NLP algorithm
      could identify a group of individuals where 4.2% would have CD (positive
      predictive value). ICD9 code search using three hits as the cut-off had a
      sensitivity of 17.1% and a specificity of 88.5% (positive predictive value was
      0.9%). DISCUSSION AND CONCLUSIONS: This study shows that computerized EMR-based
      algorithms can help identify patients at high risk of CD. NLP-based techniques
      demonstrate higher sensitivity and positive predictive values than algorithms
      based on ICD9 code searches.

PMID- 23956017
TI  - Identifying phenotypic signatures of neuropsychiatric disorders from electronic
      medical records.
AB  - OBJECTIVE: Mental illness is the leading cause of disability in the USA, but
      boundaries between different mental illnesses are notoriously difficult to
      define. Electronic medical records (EMRs) have recently emerged as a powerful new
      source of information for defining the phenotypic signatures of specific
      diseases. We investigated how EMR-based text mining and statistical analysis
      could elucidate the phenotypic boundaries of three important neuropsychiatric
      illnesses-autism, bipolar disorder, and schizophrenia. METHODS: We analyzed the
      medical records of over 7000 patients at two facilities using an automated text
      processing pipeline to annotate the clinical notes with Unified Medical Language
      System codes and then searching for enriched codes, and associations among codes,
      that were representative of the three disorders. We used dimensionality-reduction
      techniques on individual patient records to understand individual-level
      phenotypic variation within each disorder, as well as the degree of overlap among
      disorders. RESULTS: We demonstrate that automated EMR mining can be used to
      extract relevant drugs and phenotypes associated with neuropsychiatric disorders
      and characteristic patterns of associations among them. Patient-level analyses
      suggest a clear separation between autism and the other disorders, while
      revealing significant overlap between schizophrenia and bipolar disorder. They
      also enable localization of individual patients within the phenotypic 'landscape'
      of each disorder. CONCLUSIONS: Because EMRs reflect the realities of patient care
      rather than idealized conceptualizations of disease states, we argue that
      automated EMR mining can help define the boundaries between different mental
      illnesses, facilitate cohort building for clinical and genomic studies, and
      reveal how clear expert-defined disease boundaries are in practice.

PMID- 23956018
TI  - Electronic health records based phenotyping in next-generation clinical trials: a
      perspective from the NIH Health Care Systems Collaboratory.
AB  - Widespread sharing of data from electronic health records and patient-reported
      outcomes can strengthen the national capacity for conducting cost-effective
      clinical trials and allow research to be embedded within routine care delivery.
      While pragmatic clinical trials (PCTs) have been performed for decades, they now
      can draw on rich sources of clinical and operational data that are continuously
      fed back to inform research and practice. The Health Care Systems Collaboratory
      program, initiated by the NIH Common Fund in 2012, engages healthcare systems as
      partners in discussing and promoting activities, tools, and strategies for
      supporting active participation in PCTs. The NIH Collaboratory consists of seven
      demonstration projects, and seven problem-specific working group 'Cores', aimed
      at leveraging the data captured in heterogeneous 'real-world' environments for
      research, thereby improving the efficiency, relevance, and generalizability of
      trials. Here, we introduce the Collaboratory, focusing on its Phenotype, Data
      Standards, and Data Quality Core, and present early observations from researchers
      implementing PCTs within large healthcare systems. We also identify gaps in
      knowledge and present an informatics research agenda that includes identifying
      methods for the definition and appropriate application of phenotypes in diverse
      healthcare settings, and methods for validating both the definition and execution
      of electronic health records based phenotypes.

PMID- 23956019
TI  - What are ventilation defects in asthma?
AB  - BACKGROUND: Hyperpolarised (3)He MRI provides a way to visualise regional
      pulmonary functional abnormalities that in asthma are thought to be related to
      airway morphological abnormalities. However, the exact aetiology of ventilation
      defects in asthma is not well understood. OBJECTIVE: To better understand the
      determinants of ventilation defects in asthma, we evaluated well-established
      clinical as well as (3)He MRI and X-ray CT airway measurements in healthy
      subjects and subjects with asthma. METHODS: Thirty-four subjects (n=26 subjects
      with asthma, n=8 healthy volunteers) underwent MRI, spirometry, plethysmography,
      fraction of exhaled nitric oxide analysis, methacholine challenge and CT for a
      region-of-interest proximal to ventilation defects. For subjects who consented to
      CT (n=18 subjects with asthma, n=5 healthy volunteers), we evaluated 3(rd) to 5th
      generation airway wall area and wall thickness per cent and lumen area. RESULTS:
      Seventeen subjects with asthma (17/26=65%) had visually obvious evidence of (3)He
      ventilation defects prior to bronchoprovocation and nine subjects with asthma had
      no ventilation defects prior to bronchoprovocation (9/26=35%). Subjects with
      asthma with defects were older (p=0.01) with worse forced expiratory volume in 1
      s (FEV1)/forced vital capacity (p=0.0003), airways resistance (p=0.004), fraction
      of exhaled nitric oxide (p=0.03), greater bronchoprovocation concentration of
      methacholine that reduced FEV1 by 20% (p=0.008) and wall thickness per cent
      (p=0.02) compared with subjects with asthma without defects. There was a moderate
      correlation for wall area per cent with ventilation defect per cent (r=0.43,
      p=0.04). CONCLUSIONS: Subjects with asthma with (3)He ventilation defects were
      older with significantly worse airway hyper-responsiveness, inflammation and
      airway remodelling but similar FEV1 as subjects with asthma without defects;
      hyperpolarised (3)He ventilation abnormalities were spatially and quantitatively
      related to abnormally remodelled airways.

PMID- 23956020
TI  - Pneumonia in low and middle income countries: progress and challenges.
AB  - Pneumonia remains the leading cause of childhood mortality and the most common
      reason for adult hospitalisation in low and middle income countries, despite
      advances in preventative and management strategies. In the last decade, pneumonia
      mortality in children has fallen to approximately 1.3 million cases in 2011, with
      most deaths occurring in low income countries. Important recent advances include
      more widespread implementation of protein-polysaccharide conjugate vaccines
      against Haemophilus influenzae type B and Streptococcus pneumoniae,
      implementation of case-management algorithms and better prevention and treatment
      of HIV. Determining the aetiology of pneumonia is challenging in the absence of
      reliable diagnostic tests. High uptake of new bacterial conjugate vaccines may
      impact on pneumonia burden, aetiology and empiric therapy but implementation in
      immunisation programmes in many low and middle income countries remains an
      obstacle. Widespread implementation of currently effective preventative and
      management strategies for pneumonia remains challenging in many low and middle
      income countries. 

PMID- 23956021
TI  - Nucleus rostrolateralis: an expansion of the epithalamus in some actinopterygii.
AB  - The diencephalic nucleus rostrolateralis (RL) in the African butterfly fish
      (Pantodon buchholzi) is a brain nucleus identified in fewer than a dozen of the
      ~25,000 species of actinopterygian fishes. Located in the rostrolateral
      diencephalon, this nucleus in Pantodon receives direct and indirect visual input
      from the superior visual field. Its lack of precedent or consistent phylogenetic
      expression creates a difficulty in interpreting the functional role of this
      nucleus within the visual system. By tracing experiments, RL was found to be
      afferent to nucleus interpeduncularis (IP) and the target of cells from the
      subpallium of the telencephalon. RL is a component of a descending telencephalic
      pathway involved in at least one behavior at the intersection of limbic and
      somatic activities--feeding. The parallelism between the ventral telencephalon-
      RL--IP and the limbic/striatal--habenula--IP pathway (the dorsal diencephalic
      conduction system, DDCS) suggests that RL is a component within the DDCS.
      Moreover, the hodological connections of RL suggest that RL is likely a
      hypertrophy of the lateral habenula.

PMID- 23956022
TI  - Total synthesis and structural revision of laurefurenynes A and B.
AB  - Structural reassignment: A total synthesis of the proposed structure of (-)
      laurefurenyne A has been accomplished that relies on organocatalytic aldehyde
      alpha-chlorination and a flexible chlorohydrin-based strategy for
      stereocontrolled access to the bis-tetrahydrofuran core of the natural product.
      Analysis of incongruities between the (1) H NMR spectra of synthetic and natural
      material led to a configurational reassignment for the natural product, which was
      also confirmed by total synthesis.

PMID- 23956023
TI  - Preclinical high-dose acetaminophen with N-acetylcysteine rescue enhances the
      efficacy of cisplatin chemotherapy in atypical teratoid rhabdoid tumors.
AB  - BACKGROUND: Atypical teratoid rhabdoid tumors (AT-RT) are pediatric tumors of the
      central nervous system with limited treatment options and poor survival rate. We
      investigated whether enhancing chemotherapy toxicity by depleting intracellular
      glutathione (GSH; a key molecule in cisplatin resistance) with high dose
      acetaminophen (AAP), may improve therapeutic efficacy in AT-RT in vitro.
      PROCEDURE: BT16 (cisplatin-resistant) and BT12 (cisplatin-sensitive) AT-RT cell
      lines were treated with combinations of AAP, cisplatin, and the anti-oxidant N
      acetylcysteine (NAC). Cell viability, GSH and peroxide concentrations,
      mitochondrial damage, and apoptosis were evaluated in vitro. RESULTS: AAP
      enhanced cisplatin cytotoxicity in cisplatin-resistant BT16 cells but not
      cisplatin-sensitive BT12 cells. Baseline GSH levels were elevated in BT16 cells
      compared to BT12 cells, and AAP decreased GSH to a greater magnitude in BT16
      cells than BT12 cells. Unlike BT12 cells, BT16 cells did not have elevated
      peroxide levels upon treatment with cisplatin alone, but did have elevated levels
      when treated with AAP + cisplatin. Both cell lines had markedly increased
      mitochondrial injury when treated with AAP + cisplatin relative to either drug
      treatment alone. The enhanced toxic effects were partially reversed with
      concurrent administration of NAC. CONCLUSIONS: Our results suggest that AAP could
      be used as a chemo-enhancement agent to potentiate cisplatin chemotherapeutic
      efficacy particularly in cisplatin-resistant AT-RT tumors with high GSH levels in
      clinical settings.

PMID- 23956024
TI  - Efficacy of a text message-based smoking cessation intervention for young people:
      a cluster randomized controlled trial.
AB  - BACKGROUND: Smoking prevalence remains high, particularly among adolescents and
      young adults with lower educational levels, posing a serious public health
      problem. There is limited evidence of effective smoking cessation interventions
      in this population. OBJECTIVE: To test the efficacy of an individually tailored,
      fully automated text messaging (short message service, SMS)-based intervention
      for smoking cessation in young people. METHODS: A 2-arm cluster randomized
      controlled trial, using school class as the randomization unit, was conducted to
      test the efficacy of the SMS text messaging intervention compared to an
      assessment-only control group. Students who smoked were proactively recruited via
      online screening in vocational school classes. Text messages, tailored to
      demographic and smoking-related variables, were sent to the participants of the
      intervention group at least 3 times per week over a period of 3 months. A follow
      up assessment was performed 6 months after study inclusion. The primary outcome
      measure was 7-day smoking abstinence. Secondary outcomes were 4-week smoking
      abstinence, cigarette consumption, stage of change, and attempts to quit smoking.
      We used regression models controlling for baseline differences between the study
      groups to test the efficacy of the intervention. Both complete-case analyses
      (CCA) and intention-to-treat analyses (ITT) were performed. Subgroup analyses
      were conducted for occasional and daily smokers. RESULTS: A total of 2638
      students in 178 vocational school classes in Switzerland participated in the
      online screening. Overall, 1012 persons met the inclusion criteria for study
      participation, and 755 persons (74.6%) participated in the study (intervention:
      n=372; control: n=383). Of the 372 program participants, 9 (2.4%) unsubscribed
      from the program during the intervention period. Six-month follow-up data were
      obtained for 559 study participants (74.0%). The 7-day smoking abstinence rate at
      follow-up was 12.5% in the intervention group and 9.6% in the control group (ITT:
      P=.92). No differences between the study groups were observed in 4-week point
      prevalence abstinence rates. The decrease in the mean number of cigarettes smoked
      per day from baseline to follow-up was higher in the intervention group than in
      the control group (ITT: P=.002). No differences between the groups were observed
      in stage of change (ITT: P=.82) and quit attempts (ITT: P=.38). The subgroup
      analyses revealed lower cigarette consumption in both occasional and daily
      smokers in the intervention group compared to the control group. Occasional
      smokers in the intervention group made more attempts to quit smoking than
      occasional smokers in the control group. CONCLUSIONS: This study demonstrated the
      potential of an SMS text message-based intervention to reach a high proportion of
      young smokers with low education levels. The intervention did not have
      statistically significant short-term effects on smoking cessation; however, it
      resulted in statistically significant lower cigarette consumption. Additionally,
      it resulted in statistically significant more attempts to quit smoking in
      occasional smokers. TRIAL REGISTRATION: International Standard Randomized
      Controlled Trial Number (ISRCTN): 19739792; http://www.controlled
      trials.com/ISRCTN19739792 (Archived by WebCite at
      http://webcitation.org/6IGETTHmr).

PMID- 23956025
TI  - Breast implants and anaplastic large-cell lymphoma: a danish population-based
      cohort study.
AB  - BACKGROUND: A potential link between breast implants and anaplastic large-cell
      lymphoma (ALCL) has been suggested. METHODS: We examined lymphoma occurrence in a
      nationwide cohort of 19,885 Danish women who underwent breast implant surgery
      during 1973-2010. Standardized incidence ratios (SIR), with 95% confidence
      intervals (CI), for ALCL and lymphoma overall associated with breast implantation
      were calculated. RESULTS: During 179,246 person-years of follow-up, we observed
      31 cases of lymphoma among cohort members. No cases of ALCL were identified. SIRs
      for ALCL and lymphoma overall were zero (95% CI, 0-10.3) and 1.20 (95% CI, 0.82
      1.70), respectively. CONCLUSIONS: In our nationwide cohort study, we did not find
      an increased risk of lymphoma in general, or ALCL in particular, among Danish
      women who underwent breast implantation. However, our evaluation of ALCL risk was
      limited by the rarity of the disease. IMPACT: Our results do not support an
      association between breast implants and ALCL and are consistent with other
      studies on cancer risk and breast implants.

PMID- 23956026
TI  - Predicting cancer prognosis using interactive online tools: a systematic review
      and implications for cancer care providers.
AB  - Cancer prognosis is of keen interest for patients with cancer, their caregivers,
      and providers. Prognostic tools have been developed to guide patient-physician
      communication and decision-making. Given the proliferation of prognostic tools,
      it is timely to review existing online cancer prognostic tools and discuss
      implications for their use in clinical settings. Using a systematic approach, we
      searched the Internet, Medline, and consulted with experts to identify existing
      online prognostic tools. Each was reviewed for content and format. Twenty-two
      prognostic tools addressing 89 different cancers were identified. Tools primarily
      focused on prostate (n = 11), colorectal (n = 10), breast (n = 8), and melanoma
      (n = 6), although at least one tool was identified for most malignancies. The
      input variables for the tools included cancer characteristics (n = 22), patient
      characteristics (n = 18), and comorbidities (n = 9). Effect of therapy on
      prognosis was included in 15 tools. The most common predicted outcome was cancer
      specific survival/mortality (n = 17). Only a few tools (n = 4) suggested patients
      as potential target users. A comprehensive repository of online prognostic tools
      was created to understand the state-of-the-art in prognostic tool availability
      and characteristics. Use of these tools may support communication and
      understanding about cancer prognosis. Dissemination, testing, refinement of
      existing, and development of new tools under different conditions are needed.

PMID- 23956030
TI  - The elevated gene expression level of the A(2B) adenosine receptor is associated
      with hyperglycemia in women with gestational diabetes mellitus.
AB  - BACKGROUND: Adenosine receptors denoted by A1 , A2A , A2B , and A3 and encoded by
      ADORA1, ADORA2A, ADORA2B, and ADORA3 genes, respectively, are adenosine-activated
      G-protein-coupled receptors that play an important role in obesity and type 2
      diabetes mellitus. However, little is known about their significance in
      gestational diabetes mellitus (GDM). The purpose of this study was to investigate
      whether there are changes in leukocyte AR expression in GDM patients and whether
      these alterations are linked to well-known diabetic genes. METHODS: Leukocytes
      were isolated from the blood of normal glucose tolerant (NGT; n = 35) and GDM (n
      = 82) pregnant women, and expression of ARs was determined by a semi-quantitative
      polymerase chain reaction (PCR). Univariate correlation analysis was performed to
      investigate associations between expression of ARs and anthropometric and
      metabolic parameters of patients. Furthermore, the identification of diabetic
      genes linked to significantly differentiated leukocyte adenosine receptors
      expression in GDM women was also carried out with the use of the human diabetes
      RT(2) profiler PCR arrays. RESULTS: ADORA2B mRNA expression was significantly
      higher in GDM versus NGT pregnant women (p < 0.05), and positively correlated
      with the glucose level at 1-h 75-g oral glucose tolerance test (OGTT; r = 0.21, p
      = 0.044). Nineteen diabetic genes linked to leukocyte ADORA2B overexpression
      associated with hyperglycemia in GDM women were also identified. CONCLUSIONS:
      Maternal leukocyte ADORA2B overexpression is associated with hyperglycemia in GDM
      subjects, and it is accompanied by complex alterations in the expression of
      diabetes-related genes involved in insulin action, carbohydrate and lipid
      metabolism, oxidative stress, and inflammation.

PMID- 23956027
TI  - Assessment of incident spine and hip fractures in women and men using finite
      element analysis of CT scans.
AB  - Finite element analysis of computed tomography (CT) scans provides noninvasive
      estimates of bone strength at the spine and hip. To further validate such
      estimates clinically, we performed a 5-year case-control study of 1110 women and
      men over age 65 years from the AGES-Reykjavik cohort (case = incident spine or
      hip fracture; control = no incident spine or hip fracture). From the baseline CT
      scans, we measured femoral and vertebral strength, as well as bone mineral
      density (BMD) at the hip (areal BMD only) and lumbar spine (trabecular volumetric
      BMD only). We found that for incident radiographically confirmed spine fractures
      (n = 167), the age-adjusted odds ratio for vertebral strength was significant for
      women (2.8, 95% confidence interval [CI] 1.8 to 4.3) and men (2.2, 95% CI 1.5 to
      3.2) and for men remained significant (p = 0.01) independent of vertebral
      trabecular volumetric BMD. For incident hip fractures (n = 171), the age-adjusted
      odds ratio for femoral strength was significant for women (4.2, 95% CI 2.6 to
      6.9) and men (3.5, 95% CI 2.3 to 5.3) and remained significant after adjusting
      for femoral neck areal BMD in women and for total hip areal BMD in both sexes;
      fracture classification improved for women by combining femoral strength with
      femoral neck areal BMD (p = 0.002). For both sexes, the probabilities of spine
      and hip fractures were similarly high at the BMD-based interventional thresholds
      for osteoporosis and at corresponding preestablished thresholds for "fragile bone
      strength" (spine: women <= 4500 N, men <= 6500 N; hip: women <= 3000 N, men <=
      3500 N). Because it is well established that individuals over age 65 years who
      have osteoporosis at the hip or spine by BMD criteria should be considered at
      high risk of fracture, these results indicate that individuals who have fragile
      bone strength at the hip or spine should also be considered at high risk of
      fracture.

PMID- 23956031
TI  - Folate decorated magnetite nanoparticles: synthesis and targeted therapy against
      ovarian cancer.
AB  - Doxorubicin (DOX) loaded folate-coated magnetic Fe3 O4 nanoparticles (MNPs) were
      prepared by co-precipitation and emulsification cross-linking method and uniform
      NPs with an average particle size of 15 (bare) and 35 nm (FA-MNPs), with high
      encapsulation efficiencies (EE), were obtained. The release profiles of
      conjugated DOX showed that pH 6.0 provided suitable conditions for proper drug
      release. IC50 analysis of C30 and CP70 cell lines after 96 h (4 days) exposure to
      DOX-FA-MNPs showed that the most significant IC50 were at 5.4 +/- 0.6 and 11.2 +/
      2.7 mM DOX loaded onto the FA-MNPs. Thus CP70 cells are more resistant to lower
      concentrations of drug compared to C30 cells (P < 0.05). C30 and CP70 cells
      reached 91 and 81.8% apoptosis after administration of DOX-FA-MNPs (5 mg/mL)
      compared to 49.2 and 46.6% after administration of the free drug, respectively (P
      < 0.05). this study indicates that FA modified MNPs enhances the DOX-induced
      apoptosis in both of the human ovarian cancer cell lines with sharp decreases in
      the levels of bcl-2 and surviving, and increased expression of caspase-3.

PMID- 23956032
TI  - Advance of RNA interference technique in Hemipteran insects.
AB  - RNA interference (RNAi) suppressed the expression of the target genes by post
      transcriptional regulation and the double-stranded RNA (dsRNA) mediated gene
      silencing has been a conserved mechanism in many eukaryotes, which prompted RNAi
      to become a valuable tool for unveiling the gene function in many model insects.
      Recent research attested that RNAi technique can be also effective in
      downregulation target genes in Hemipteran insects. In this review, we collected
      the researches of utilizing RNAi technique in gene functional analysis in
      Hemipteran insects, highlighted the methods of dsRNA/siRNA uptake by insects and
      discussed the knock-down efficiency of these techniques. Although the RNA
      interference technique has drawbacks and obscure points, our primary goal of this
      review is try to exploit it for further discovering gene functions and pest
      control tactic in the Hemipteran insects.

PMID- 23956033
TI  - Previous encapsulation response enhances within individual protection against
      fungal parasite in the mealworm beetle Tenebrio molitor.
AB  - Immune defenses of insects show either broad reactions or specificity and
      durability of induced protection against attacking parasites and pathogens. In
      this study, we tested whether encapsulation response against nylon monofilament
      increases between two attempts of activation of immune system in mealworm beetles
      Tenebrio molitor, and whether previous exposure to nylon monofilament may also
      increase protection against an entomopathogenic fungus. We found that survival of
      beetles subjected to immune activation by nylon implant and subsequent fungal
      exposure a week later was significantly higher than survival of beetles which had
      been subjected to fungal infection only. This result suggests that previous
      immune activation by the nylon implant may be considered as broad spectrum
      "immune priming" which helps to fight not only the same intruder but also other
      parasites. 

PMID- 23956034
TI  - Predictors of survival in carcinoma ex pleomorphic adenoma.
AB  - BACKGROUND: Carcinoma ex pleomorphic adenoma (Ca ex PA) is a high-grade carcinoma
      arising from benign pleomorphic adenoma. This is the first population-level
      analysis of prognosis and prognostic features of parotid Ca ex PA. METHODS: The
      Surveillance, Epidemiology, and End Results (SEER) database (1988-2009) was used
      to identify 278 patients with parotid Ca ex PA. RESULTS: Extraparenchymal
      extension of the primary tumor was associated with cervical metastasis (35.7% vs
      2.9%; p < .001). Independent predictors of disease-specific survival (DSS) were
      race (hazard ratio [HR], 7.12; 95% confidence interval [CI], 2.56-19.82), distant
      metastases (HR, 18.99; 95% CI, 5.06-71.21), and multiple metastatic lymph nodes
      (HR, 9.48; 95% CI, 4.14-21.71). Patients with multiple cervical lymph node
      metastases had decreased 5-year DSS compared with patients with <=1 positive
      lymph node (42.7% vs 85.9%; p < .001). CONCLUSION: The presence of 2 or more
      cervical lymph node metastases identifies patients with Ca ex PA with a poor
      prognosis.

PMID- 23956035
TI  - Localized treatments using commercial dust and liquid formulations of fipronil
      against Coptotermes formosanus (Isoptera: Rhinotermitidae) in the laboratory.
AB  - Use of proper application methods and formulations of termiticides are important
      to reduce their negative impact to the environment. In this study, we conducted
      laboratory experiments to determine the effect of localized treatments with
      commercial dust and liquid formulations of fipronil against Formosan subterranean
      termites, Coptotermes formosanus Shiraki. The test arena consisted of a specially
      designed 16-chambered structure with a center chamber connected to 5 foraging
      chambers that themselves were connected to 10 additional foraging chambers. One
      peripheral chamber received a liquid or dust treatment and termites were released
      in the center chamber. Results showed that >91% of the termites were dead within
      the 9-d test period despite the localized treatment of only 1 foraging chamber.
      Termites that were still alive after 9 d were transferred to an untreated dish
      and held for 10 more days. The majority of those termites were dead and the rest
      were moribund on day 19. Regardless of the specific dish treated, both
      formulations of fipronil were found to be highly efficacious. Termites did not
      exhibit repellency to either formulation. Our results suggest that localized (or
      spot) treatment with either commercially available dust or liquid formulations of
      fipronil can be a viable option for control of a termite infestation where
      complete soil drenching is not desirable.

PMID- 23956036
TI  - Mesoporous silica nanoparticle pretargeting for PET imaging based on a rapid
      bioorthogonal reaction in a living body.
AB  - Last-minute labeling: Mesoporous silica nanoparticles (MSNs) were modified with a
      very short half-life fluorine-18-labeled azide radiotracer by a cycloaddition
      reaction after the MSNs had reached the tumor site in mice. The tumor could then
      be visualized successfully with positron emission tomography. 

PMID- 23956037
TI  - Solution-grown organic single-crystalline p-n junctions with ambipolar charge
      transport.
AB  - Organic single-crystalline p-n junctions are grown from mixed solutions. First,
      C60 crystals (n-type) form and, subsequently, C8-BTBT crystals (p-type) nucleate
      heterogeneously on the C60 crystals. Both crystals continue to grow
      simultaneously into single-crystalline p-n junctions that exhibit ambipolar
      charge transport characteristics. This work provides a platform to study organic
      single-crystalline p-n junctions. 

PMID- 23956038
TI  - One-step formation of a single atomic-layer transistor by the selective
      fluorination of a graphene film.
AB  - In this study, the scalable and one-step fabrication of single atomic-layer
      transistors is demonstrated by the selective fluorination of graphene using a low
      damage CF4 plasma treatment, where the generated F-radicals preferentially
      fluorinated the graphene at low temperature (<200  degrees C) while defect
      formation was suppressed by screening out the effect of ion damage. The chemical
      structure of the C-F bonds is well correlated with their optical and electrical
      properties in fluorinated graphene, as determined by X-ray photoelectron
      spectroscopy, Raman spectroscopy, and optical and electrical characterizations.
      The electrical conductivity of the resultant fluorinated graphene (F-graphene)
      was demonstrated to be in the range between 1.6 kOmega/sq and 1 MOmega/sq by
      adjusting the stoichiometric ratio of C/F in the range between 27.4 and 5.6,
      respectively. Moreover, a unique heterojunction structure of semi
      metal/semiconductor/insulator can be directly formed in a single layer of
      graphene using a one-step fluorination process by introducing a Au thin-film as a
      buffer layer. With this heterojunction structure, it would be possible to
      fabricate transistors in a single graphene film via a one-step fluorination
      process, in which pristine graphene, partial F-graphene, and highly F-graphene
      serve as the source/drain contacts, the channel, and the channel isolation in a
      transistor, respectively. The demonstrated graphene transistor exhibits an on-off
      ratio above 10, which is 3-fold higher than that of devices made from pristine
      graphene. This efficient transistor fabrication method produces electrical
      heterojunctions of graphene over a large area and with selective patterning,
      providing the potential for the integration of electronics down to the single
      atomic-layer scale. 

PMID- 23956039
TI  - Invasion history of Solenopsis invicta (Hymenoptera: Formicidae) in Fujian, China
      based on mitochondrial DNA and its implications in development of a control
      strategy.
AB  - One of the most invasive species worldwide, Solenopsis invicta Buren, has been
      described in China since 2003. Recent studies have suggested that China
      populations are the result of introductions from the USA; however, detailed
      molecular studies need to be performed in order to understand the expansion and
      potential multiple introductions from other countries into China. As there were
      populations of red imported fire ant, S. invicta in different areas and with
      different methods of introduction, mitochondrial cytochrome oxidase I gene was
      used as a marker from 12 populations in four cities in Fujian Province, China, to
      determine the relationship of invasion among these populations. The three most
      common haplotypes previously describe in invasive populations of S. invicta: H5,
      H22 and H36, were found in Fujian. However, frequencies in each city were
      different. For instance, three populations from Longyan city which invaded with
      waste plastics, shared haplotype H5. Populations from Xiamen city and Jinjiang
      city which dispersed with nursery stock, sward and scrap leather, shared
      haplotype H22. The population from Nanyan village of Xinluo district, Longyan
      city, bore haplotype H36. Mitochondrial data reveals that the invasion history of
      S. invicta in Fujian Province is complex, including multiple invasions probably
      from other provinces within China. Security measures to prevent S. invicta
      spreading within China are as important as from overseas. 

PMID- 23956040
TI  - Suitability of three Ostrinia species as hosts for Macrocentrus cingulum: a
      comparison of their encapsulation abilities.
AB  - Two cornborer species, Ostrinia furnacalis (Lepidoptera: Crambidae) and O.
      nubilalis, are major corn pests in Asia and Europe, respectively. In both
      continents, the larval endoparasitoid Macrocentrus cingulum (Hymenoptera:
      Braconidae) develops on another, closely related stemborer, O. scapulalis, which
      feeds on mugwort and other dicotyledons. M. cingulum also emerges from O.
      furnacalis in Asia and O. nubilalis in North America, but not from O. nubilalis
      in Europe. We assessed the ability of three populations of each of the three
      Ostrinia species to encapsulate foreign bodies of a size similar to that of a M.
      cingulum egg. We conclude that variations in encapsulation ability alone cannot
      account for the differences observed in the field between parasite emergence
      rates in these different host species and geographic areas. 

PMID- 23956041
TI  - Effects of PTHrP on expression of MMP9 and MMP13 in sika deer antler
      chondrocytes.
AB  - Deer antlers are the only mammalian appendages to display an annual cycle of full
      regeneration. However, little is known about the molecular mechanisms of antler
      regeneration. Our previous study has demonstrated that parathyroid hormone
      related peptide (PTHrP) can promote proliferation of antler chondrocytes and
      inhibit its differentiation, but the mechanism underlying such regulation is not
      fully understood. We have determined the role of PTHrP on the mRNA expression of
      matrix metalloproteinase-9 (MMP9) and MMP13 in the antler chondrocytes. The
      possible pathways that transduce PTHrP effects were examined. In situ
      hybridization showed that MMP9 and MMP13 were mainly localized in the dermal
      fibroblasts, perichondrium, and cartilage in the sika deer antler, of which MMP9
      and MMP13 were highly expressed in the chondrocytes. Exogenous PTHrP could
      inhibit the expression of MMP9 and MMP13 in the antler chondrocytes. The
      inhibitory effect of PTHrP on MMP9 was abolished by JNK inhibitor, SP600125,
      while P38MAPK inhibitor SB203850 and PKC inhibitor GF109203X could rescue the
      inhibitory effect of PTHrP on MMP13. The results suggest that PTHrP can inhibit
      MMP9 expression by JNK signaling pathway and MMP13 expression by p38MAPK and PKC
      signaling pathways in the antler chondrocytes. Thus PTHrP is involved in the
      control of antler chondrocytes maturation and cartilage matrix degradation. 

PMID- 23956042
TI  - Crowdsourcing black market prices for prescription opioids.
AB  - BACKGROUND: Prescription opioid diversion and abuse are major public health
      issues in the United States and internationally. Street prices of diverted
      prescription opioids can provide an indicator of drug availability, demand, and
      abuse potential, but these data can be difficult to collect. Crowdsourcing is a
      rapid and cost-effective way to gather information about sales transactions. We
      sought to determine whether crowdsourcing can provide accurate measurements of
      the street price of diverted prescription opioid medications. OBJECTIVE: To
      assess the possibility of crowdsourcing black market drug price data by cross
      validation with law enforcement officer reports. METHODS: Using a crowdsourcing
      research website (StreetRx), we solicited data about the price that site visitors
      paid for diverted prescription opioid analgesics during the first half of 2012.
      These results were compared with a survey of law enforcement officers in the
      Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System,
      and actual transaction prices on a "dark Internet" marketplace (Silk Road).
      Geometric means and 95% confidence intervals were calculated for comparing prices
      per milligram of drug in US dollars. In a secondary analysis, we compared prices
      per milligram of morphine equivalent using standard equianalgesic dosing
      conversions. RESULTS: A total of 954 price reports were obtained from
      crowdsourcing, 737 from law enforcement, and 147 from the online marketplace.
      Correlations between the 3 data sources were highly linear, with Spearman rho of
      0.93 (P<.001) between crowdsourced and law enforcement, and 0.98 (P<.001) between
      crowdsourced and online marketplace. On StreetRx, the mean prices per milligram
      were US$3.29 hydromorphone, US$2.13 buprenorphine, US$1.57 oxymorphone, US$0.97
      oxycodone, US$0.96 methadone, US$0.81 hydrocodone, US$0.52 morphine, and US$0.05
      tramadol. The only significant difference between data sources was morphine, with
      a Drug Diversion price of US$0.67/mg (95% CI 0.59-0.75) and a Silk Road price of
      US$0.42/mg (95% CI 0.37-0.48). Street prices generally followed clinical
      equianalgesic potency. CONCLUSIONS: Crowdsourced data provide a valid estimate of
      the street price of diverted prescription opioids. The (ostensibly free) black
      market was able to accurately predict the relative pharmacologic potency of
      opioid molecules.

PMID- 23956043
TI  - A geometric morphometric analysis of the medial tibial condyle of African
      hominids.
AB  - Although the hominid knee has been heavily scrutinized, shape variation of the
      medial tibial condyle has yet to be described. Humans, chimpanzees, and gorillas
      differ in the shape of their medial femoral condyles and in their capacity for
      external and internal rotation of the tibia relative to the femur. I hypothesize
      that these differences should be reflected in the shape of the medial tibial
      condyle of these hominids. Here I use geometric morphometric techniques to
      uncover shape differences between the medial tibial condyles of humans,
      chimpanzees, and gorillas. Humans are distinguished from the other two species by
      having a much more oval-shaped medial tibial condyle, while those of chimpanzees
      and gorillas are more triangular in outline. Gorillas (especially males) are
      distinguished by having more concavely-curved condyles (mediolateral direction),
      which is interpreted as an effect of heavy loading through the medial compartment
      of the knee in conjunction with differences in the degree of arboreality.

PMID- 23956044
TI  - Postnatal establishment of allelic Galphas silencing as a plausible explanation
      for delayed onset of parathyroid hormone resistance owing to heterozygous Galphas
      disruption.
AB  - Pseudohypoparathyroidism type-Ia (PHP-Ia), characterized by renal proximal
      tubular resistance to parathyroid hormone (PTH), results from maternal mutations
      of GNAS that lead to loss of alpha-subunit of the stimulatory G protein (Galphas)
      activity. Galphas expression is paternally silenced in the renal proximal tubule,
      and this genomic event is critical for the development of PTH resistance, as
      patients display impaired hormone action only if the mutation is inherited
      maternally. The primary clinical finding of PHP-Ia is hypocalcemia, which can
      lead to various neuromuscular defects including seizures. PHP-Ia patients
      frequently do not present with hypocalcemia until after infancy, but it has
      remained uncertain whether PTH resistance occurs in a delayed fashion. Analyzing
      reported cases of PHP-Ia with documented GNAS mutations and mice heterozygous for
      disruption of Gnas, we herein determined that the manifestation of PTH resistance
      caused by the maternal loss of Galphas, ie, hypocalcemia and elevated serum PTH,
      occurs after early postnatal life. To investigate whether this delay could
      reflect gradual development of paternal Galphas silencing, we then analyzed renal
      proximal tubules isolated by laser capture microdissection from mice with either
      maternal or paternal disruption of Gnas. Our results revealed that, whereas
      expression of Galphas mRNA in this tissue is predominantly from the maternal Gnas
      allele at weaning (3 weeks postnatal) and in adulthood, the contributions of the
      maternal and paternal Gnas alleles to Galphas mRNA expression are equal at
      postnatal day 3. In contrast, we found that paternal Galphas expression is
      already markedly repressed in brown adipose tissue at birth. Thus, the mechanisms
      silencing the paternal Galphas allele in renal proximal tubules are not
      operational during early postnatal development, and this finding correlates well
      with the latency of PTH resistance in patients with PHP-Ia.

PMID- 23956045
TI  - Total synthesis of stemaphylline N-oxide and related C9a-epimeric analogues.
AB  - Winning the relay: The first total synthesis of stemaphylline N-oxide has been
      completed utilizing a bistandem relay ring-closing-metathesis (RRCM) strategy,
      necessitated by the conformation of the requisite tetraene. This effort also gave
      unnatural 9a-epi-stemaphylline and 9a-epi-stemaphylline N-oxide. 

PMID- 23956046
TI  - Regulation of genes in the arachidonic acid metabolic pathway by RNA processing
      and RNA-mediated mechanisms.
AB  - Arachidonic acid (AA) is converted by enzymes in an important metabolic pathway
      to produce molecules known collectively as eicosanoids, 20 carbon molecules with
      significant physiological and pathological functions in the human body.
      Cyclooxygenase (COX) enzymes work in one arm of the pathway to produce
      prostaglandins (PGs) and thromboxanes (TXs), while the actions of 5-lipoxygenase
      (ALOX5 or 5LO) and its associated protein (ALOX5AP or FLAP) work in the other arm
      of the metabolic pathway to produce leukotrienes (LTs). The expression of the COX
      and ALOX5 enzymes that convert AA to eicosanoids is highly regulated at the post-
      or co-transcriptional level by alternative mRNA splicing, alternative mRNA
      polyadenylation, mRNA stability, and microRNA (miRNA) regulation. This review
      article will highlight these mechanisms of mRNA modulation.

PMID- 23956048
TI  - Radionuclides and radiation doses in heavy mineral sands and other mining
      operations in Mozambique.
AB  - Sites at the littoral of Mozambique with heavy mineral sands exploited for
      ilmenite, rutile and zircon and inland mineral deposits exploited for tantalite,
      uranium and bauxite were surveyed for ambient radiation doses, and samples were
      collected for the determination of radionuclide concentrations. In heavy mineral
      sands, (238)U and (232)Th concentrations were 70+/-2 and 308+/-9 Bq kg(-1) dry
      weight (dw), respectively, whereas after separation of minerals, the
      concentrations in the ilmenite fraction were 2240+/-64 and 6125+/-485 Bq kg(-1)
      (dw), respectively. Tantalite displayed the highest concentrations with 44 738+/
      2474 Bq kg(-1) of (238)U. Radiation exposure of workers in mining facilities is
      likely to occur at levels above the dose limit for members of the public (1 mSv
      y(-1)) and therefore radiation doses should be assessed as occupational
      exposures. Local populations living in these regions in general are not exposed
      to segregated minerals with high radionuclide concentrations. However, there is
      intensive artisanal mining and a large number of artisanal miners and their
      families may be exposed to radiation doses exceeding the dose limit. A radiation
      protection programme is therefore needed to ensure radiation protection of the
      public and workers of developing mining projects. 

PMID- 23956049
TI  - Impact of primary tumor volume on local control after definitive radiotherapy for
      head and neck cancer.
AB  - BACKGROUND: The impact of primary tumor volume (pTV) on local control after
      definitive radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC) is
      unclear. METHODS: Pertinent literature was reviewed to address the impact of pTV
      on local control after definitive RT for HNSCC. RESULTS: Reproducibility of pTV
      calculations is probably influenced by interobserver variability and may be
      reduced by relying on experienced observers. The impact of pTV on local control
      after definitive RT is probably influenced by primary site. A relatively limited
      impact of pTV on local control after RT for oropharyngeal squamous cell
      carcinomas (SCCs) might be attributable to human papillomavirus (HPV) positivity.
      CONCLUSION: pTV may be a useful parameter to select patients for treatment with
      definitive RT, particularly for those with laryngeal SCCs. Patients with high
      volume primary cancers, in which the probability of local control with a
      functional larynx is low, are likely better treated with surgery.

PMID- 23956050
TI  - Needle-trap device for the sampling and determination of chlorinated volatile
      compounds.
AB  - A needle-trap device, with immobilized sorbent inside the syringe, coupled with
      GC-MS was applied for air sampling and determination of chlorinated volatile
      organic compounds such as dichloromethane, trichloromethane, and
      tetrachloromethane. The application of a needle trap packed with combination of
      three sorbents including Tenax TA, Carbopack X, and Carboxen 1000 resulted in
      detection limits of few pg for chlorinated volatile compounds and recoveries of
      99.2-102.8%. The extraction and desorption parameters were optimized within the
      study. As a result, the precision determined as RSD was equal to 5.05 and 3.03
      and 6.52% for dichloromethane, trichloromethane, and tetrachloromethane,
      respectively. The storage time for chlorinated compounds up to 48 h and
      reusability of the needle-trap device were verified. The obtained results have
      proved the ability of needle traps to compete with other solventless sampling and
      sample preparation extraction techniques. 

PMID- 23956051
TI  - Amino acids in the rhizosphere: from plants to microbes.
AB  - Often referred to as the "building blocks of proteins", the 20 canonical
      proteinogenic amino acids are ubiquitous in biological systems as the functional
      units in proteins. Sometimes overlooked are their varying additional roles that
      include serving as metabolic intermediaries, playing structural roles in
      bioactive natural products, acting as cosubstrates in enzymatic transformations,
      and as key regulators of cellular physiology. Amino acids can also serve as
      biological sources of both carbon and nitrogen and are found in the rhizosphere
      as a result of lysis or cellular efflux from plants and microbes and proteolysis
      of existing peptides. While both plants and microbes apparently prefer to take up
      nitrogen in its inorganic form, their ability to take up and use amino acids may
      confer a selective advantage in certain environments where organic nitrogen is
      abundant. Further, certain amino acids (e.g., glutamate and proline) and their
      betaines (e.g., glycine betaine) serve as compatible solutes necessary for
      osmoregulation in plants and microbes and can undergo rapid cellular flux. This
      ability is of particular importance in an ecological niche such as the
      rhizosphere, which is prone to significant variations in solute concentrations.
      Amino acids are also shown to alter key phenotypes related to plant root growth
      and microbial colonization, symbiotic interactions, and pathogenesis in the
      rhizosphere. This review will focus on the sources, transport mechanisms, and
      potential roles of the 20 canonical proteinogenic amino acids in the rhizosphere.

PMID- 23956052
TI  - Ultrathin nanosheets of vanadium diselenide: a metallic two-dimensional material
      with ferromagnetic charge-density-wave behavior.
AB  - A new metallic 2D material with high electrical conductivity (1*10(3) S m(-1))
      consists of VSe2 ultrathin nanosheets with 4-8 Se-V-Se atomic layers. This is the
      first 2D transition-metal dichalcogenide with intrinsic room-temperature
      ferromagnetism. The nanosheets increase the charge-density-wave transition
      temperature to 135 K by dimensional reduction.

PMID- 23956053
TI  - Ultrastable metallic glass.
AB  - A new metallic glass, which was created by vapour deposition at an appropriately
      high substrate temperature, shows exceptional thermal stability, and enhanced
      glass transition temperature and elastic modulus. Comparing this new material
      with other organic glasses prepared by similar routes and known as ultrastable
      glasses demonstrates the formation of ultrastable glassy materials correlates to
      the important concept of fragility. 

PMID- 23956054
TI  - Cabbage waxes affect Trissolcus brochymenae response to short-range synomones.
AB  - We show that induced synomones, emitted as a consequence of Murgantia histrionica
      activity on Brassica oleracea, are adsorbed by the epicuticular waxes of leaves
      and perceived by the egg parasitoid Trissolcus brochymenae. Leaves were exposed
      to M. histrionica females placed on the abaxial leaf surface. After 24 h, the
      leaves were treated mechanically using gum arabic, or chemically using
      chloroform, on the adaxial surface, and finally the adaxial surface was assayed
      with T. brochymenae by two-choice tests in a closed arena. Wasp females responded
      to mechanically dewaxed cabbage leaf portions with feeding punctures and
      footprints (Ff) and with feeding punctures, oviposition and footprints (FOf),
      showing no effect of wax removal. In contrast, the removal of the epicuticular
      waxes from leaf portions close to FOf, and from leaves with oviposition and
      footprints (Of), determined the lack of responses by T. brochymenae. Solvent
      extracts of different treatments were bioassayed, but only FOf triggered
      parasitoid response. Thus the detection of oviposition-induced synomones by the
      parasitoid depends on their adsorption by the epicuticular waxes. Mechanical wax
      removal from leaf portions contaminated with host footprints (f) also determined
      a lack of wasp responses, suggesting that the footprints might trigger the
      induction of a "footprint-induced synomone" adsorbed onto the epicuticular waxes
      and exploited by the parasitoid. Leaf portions with the abaxial lamina previously
      dewaxed and then contaminated by footprints (D+f) of M. histrionica did not
      affect the parasitoid response, indicating that the abaxial epicuticular waxes
      are not directly involved in the chemicals induced by M. histrionica footprints. 

PMID- 23956055
TI  - Phase 2 trial of cixutumumab in children, adolescents, and young adults with
      refractory solid tumors: a report from the Children's Oncology Group.
AB  - PURPOSE: This phase 2 study was designed to assess the efficacy of single agent
      cixutumumab (IMC-A12) and gain further information about associated toxicities
      and pharmacodynamics in children, adolescents, and young adults with recurrent or
      refractory solid tumors. PATIENTS AND METHODS: Patients with relapsed or
      refractory solid tumors were treated with 9 mg/kg of cixutumumab as a 1-hour IV
      infusion once weekly. Strata included: osteosarcoma, Ewing sarcoma,
      rhabdomyosarcoma, neuroblastoma (evaluable disease), neuroblastoma (measurable
      disease), Wilms tumor, adrenocortical carcinoma, synovial sarcoma,
      hepatoblastoma, and retinoblastoma. Correlative studies in consenting patients
      included an assessment of c-peptide, IGFBP-3, IGF-1, IGF-2, hGH, and insulin in
      consenting patients. RESULTS: One hundred sixteen patients with 114 eligible
      having a median age of 12 years (range, 2-30) were enrolled. Five patients
      achieved a partial response: 4/20 with neuroblastoma (evaluable only) and 1/20
      with rhabdomyosarcoma. Fourteen patients had stable disease for a median of 10
      cycles. Hematologic and non-hematologic toxicities were generally mild and
      infrequent. Serum IGF-1 and IGFBP-3 increased in response to therapy with
      cixutumumab. CONCLUSION: Cixutumumab is well tolerated in children with
      refractory solid tumors. Limited objective single-agent activity of cixutumumab
      was observed; however, prolonged stable disease was observed in 15% of patients.
      Ongoing studies are evaluating the toxicity and benefit of cixutumumab in
      combination with other agents that inhibit the IGF pathway.

PMID- 23956057
TI  - Survival of transplanted nests of the red wood ant Formica aquilonia
      (Hymenoptera: Formicidae): the effects of intraspecific competition and forest
      clear-cutting.
AB  - The fitness and survival of ant colonies depend on the resources near their
      nests. These resources may be limited due to poor habitat quality or by intra-
      and interspecific competitions, which in extreme cases may cause the ant colony
      to perish. We tested the effect of intraspecific competition and habitat
      degradation (forest clear-cutting) on colony survival by transplanting 26 nests
      of the red wood ant (Formica aquilonia Yarrow, 1955) in 26 different forest areas
      that contained 0-11 conspecific alien nests per hectare. F. aquilonia is highly
      dependent on canopy-dwelling aphids, thus the removal of trees should cause food
      limitation. During the course of the 4-year experiment, 9 of the forests were
      partially clear-cut. We found that while forest clear-cutting significantly
      decreased the colonies' survival, intraspecific competition did not. As a highly
      polygynous and polydomous species, F. aquilonia seems to tolerate the presence of
      alien conspecific colonies to a certain extent. 

PMID- 23956056
TI  - Overexpression of asparagine synthetase and matrix metalloproteinase 19 confers
      cisplatin sensitivity in nasopharyngeal carcinoma cells.
AB  - Platinum-based concurrent chemoradiotherapy is considered a standard treatment
      approach for locoregionally advanced nasopharyngeal carcinoma. However, only a
      minority of patients benefit from this treatment regimen compared with
      radiotherapy alone. Identification of a set of molecular markers predicting
      sensitivity of platinum-based chemotherapy may contribute to personalized
      treatment of patients with nasopharyngeal carcinoma for better clinical outcome
      with less toxicity. Previously, we generated a cisplatin-sensitive nasopharyngeal
      carcinoma cell line, S16, by clonal selection from CNE-2 cells and found that
      eIF3a is upregulated and contributes to cisplatin sensitivity by downregulating
      the synthesis of nucleotide excision repair proteins. In this study, we conducted
      a gene expression profiling analysis and found three other genes, asparagine
      synthetase (ASNS), choriogonadotropin alpha subunit (CGA), and matrix
      metalloproteinase 19 (MMP19), that are upregulated in the cisplatin-sensitive S16
      cells compared with the CNE-2 cells. However, only ASNS and MMP19, but not CGA,
      contributes to cisplatin sensitivity by potentiating cisplatin-induced DNA damage
      and apoptosis. Thus, ASNS and MMP19, along with eIF3a, are the sensitivity
      factors for cisplatin treatment and may serve as potential candidate molecular
      markers for predicting cisplatin sensitivity of advanced nasopharyngeal
      carcinoma.

PMID- 23956058
TI  - Effects of the economic crisis on smoking prevalence and number of smokers in the
      USA.
AB  - OBJECTIVE: Scanty and controversial information is available on the impact of
      macroeconomic fluctuations on smoking behaviour. No study has quantified the
      effects of fiscal crises on smoking prevalence. This study aimed to investigate
      the effects of the 2007-2008 economic crisis on smoking prevalence and number of
      smokers in the USA. METHODS: Using data from the repeated Behavioural Risk Factor
      Surveillance System (BRFSS) surveys in pre-crisis (2005-2007) and post-crisis
      (2009-2010) periods on a total of 1,981,607 US adults, we separated the expected
      (after allowance for the demographic growth of the US population, secular smoking
      prevalence trends and changes in sociodemographic characteristics) from the
      unexpected (assumed attributable to the economic crisis) changes in the number of
      smokers across different employment statuses. RESULTS: Joinpoint regression
      analysis revealed no significant changes in smoking prevalence trends over the
      period 2005-2010. The crisis resulted in an increase in the number of smokers in
      the US by 0.6 million. This is largely due to an unexpected decrease of 1.7
      million smokers among employed and an increase of 2.4 million smokers among
      unemployed individuals, whose smoking prevalence also remains extremely high in
      the post-crisis period (32.6%). CONCLUSIONS: The 2008 financial crisis had a weak
      effect on smoking prevalence. The pro-cyclical relationship (ie, the crisis
      results in a lower number of smokers) found among the employed is offset by the
      counter-cyclical relationship (ie, the crisis results in a higher number of
      smokers) found among unemployed individuals. Public health interventions should
      specifically target those in unemployment, particularly in hard times.

PMID- 23956059
TI  - How do policy advisors and practitioners prioritise the protection of children
      from secondhand smoke exposure in a country with advanced tobacco control policy?
AB  - OBJECTIVES: The aim is to extend understanding of the policy and practice
      discourses that inform the development of national tobacco control policy to
      protect children from secondhand smoke exposure (SHSE) in the home, particularly
      in a country with successful implementation of smoke-free public places
      legislation. The Scottish experience will contribute to the tobacco control
      community, particularly those countries at a similar level of tobacco control, as
      normalising discourses about protecting children from SHSE are becoming more
      widespread. DESIGN: Case study design using qualitative interviews and focus
      groups (FGs) with policy makers, health and childcare practitioners during which
      they were presented with the findings of the Reducing Families' Exposure to
      Secondhand Smoke (REFRESH) intervention and discussed the implications for their
      policy and practice priorities. SETTING: Scotland, UK PARTICIPANTS: Qualitative
      interviews and FGs were conducted with 30 policy makers and practitioners who
      were purposively recruited. RESULTS: Participants accepted the harm of SHSE to
      children; however, action is limited by political expedience due to-the
      perception of a shift of the public health priority from smoking to alcohol,
      current financial constraints, more immediate child protection concerns and
      continuing unresolved ethical arguments. CONCLUSIONS: In a country, such as
      Scotland, with advanced tobacco control strategies, there continue to be
      challenges to policy and practice development in the more contentious arena of
      the home. Children's SHSE in their homes is unequivocally accepted as an
      important health priority, but it is not currently perceived to be a top public
      health priority in Scotland.

PMID- 23956060
TI  - Developmental- and food-dependent foraging transcript levels in the desert
      locust.
AB  - Drastic changes in the environment during a lifetime require developmental and
      physiological flexibility to ensure animal survival. Desert locusts, Schistocerca
      gregaria, live in an extremely changeable environment, which alternates between
      periods of rainfall and abundant food and periods of drought and starvation. In
      order to survive, locusts display an extreme form of phenotypic plasticity that
      allows them to rapidly cope with these changing conditions by converting from a
      cryptic solitarious phase to a swarming, voracious gregarious phase. To
      accomplish this, locusts possess different conserved mediators of phenotypic
      plasticity. Recently, attention has been drawn to the possible roles of protein
      kinases in this process. In addition to cyclic AMP-dependent protein kinase
      (PKA), also cyclic GMP-dependent protein kinase (PKG), which was shown to be
      involved in changes of food-related behavior in a variety of insects, has been
      associated with locust phenotypic plasticity. In this article, we study the
      transcript levels of the S. gregaria orthologue of the foraging gene that encodes
      a PKG in different food-related, developmental and crowding conditions.
      Transcript levels of the S. gregaria foraging orthologue are highest in different
      parts of the gut and differ between isolated and crowd-reared locusts. They
      change when the availability of food is altered, display a distinct pattern with
      higher levels after a moult and decrease with age during postembryonic
      development. 

PMID- 23956061
TI  - PEITC reverse multi-drug resistance of human gastric cancer SGC7901/DDP cell
      line.
AB  - Gastric cancer is one of the leading causes of cancer death in the world and
      nearly all patients who respond initially to cisplatin later develop drug
      resistance, indicating multi-drug resistance is an essential aspect of the
      failure of treatment. Phenethyl isothiocyanate (PEITC) has been implicated in
      inhibiting metastasis of several types of human cancer. However, the effect and
      potential mechanism of PEITC reversed multi-drug resistance of human gastric
      cancer is not fully clear. We have identified the role of PEITC in multi-drug
      resistance reversal of human gastric cancer SGC7901/DDP cell line. PEITC
      inhibited cisplatin-resistant human SGC7901/DDP cell growth in a dose-dependent
      manner, causing increased apoptosis, ROS generation, glutathione depletion,
      accumulation of Rhodamine-123, decreased expression of P-glycoprotein and cell
      cycle arrest. mRNA and protein expression of the multi-drug resistance gene
      (MDR1), multi-drug resistance-associated protein (MRP1), excision repair cross
      complementing gene 1 (ERCC1), survivin, and Mad2 was decreased, and
      phosphorylation of Akt and transcriptional activation of NF-kappaB were
      suppressed. PEITC may be useful as the therapeutic strategy for overcoming multi
      drug resistance through suppressing the PI3K-Akt pathway in human gastric cancer.

PMID- 23956062
TI  - Development, implementation, and evaluation of a structured reporting web tool
      for abdominal aortic aneurysms.
AB  - BACKGROUND: The majority of radiological reports are lacking a standard
      structure. Even within a specialized area of radiology, each report has its
      individual structure with regards to details and order, often containing too much
      of non-relevant information the referring physician is not interested in. For
      gathering relevant clinical key parameters in an efficient way or to support long
      term therapy monitoring, structured reporting might be advantageous. OBJECTIVE:
      Despite of new technologies in medical information systems, medical reporting is
      still not dynamic. To improve the quality of communication in radiology reports,
      a new structured reporting system was developed for abdominal aortic aneurysms
      (AAA), intended to enhance professional communication by providing the pertinent
      clinical information in a predefined standard. METHODS: Actual state analysis was
      performed within the departments of radiology and vascular surgery by developing
      a Technology Acceptance Model. The SWOT (strengths, weaknesses, opportunities,
      and threats) analysis focused on optimization of the radiology reporting of
      patients with AAA. Definition of clinical parameters was achieved by interviewing
      experienced clinicians in radiology and vascular surgery. For evaluation, a focus
      group (4 radiologists) looked at the reports of 16 patients. The usability and
      reliability of the method was validated in a real-world test environment in the
      field of radiology. RESULTS: A Web-based application for radiological "structured
      reporting" (SR) was successfully standardized for AAA. Its organization comprises
      three main categories: characteristics of pathology and adjacent anatomy,
      measurements, and additional findings. Using different graphical widgets (eg,
      drop-down menus) in each category facilitate predefined data entries. Measurement
      parameters shown in a diagram can be defined for clinical monitoring and be
      adducted for quick adjudications. Figures for optional use to guide and
      standardize the reporting are embedded. Analysis of variance shows decreased
      average time required with SR to obtain a radiological report compared to free
      text reporting (P=.0001). Questionnaire responses confirm a high acceptance rate
      by the user. CONCLUSIONS: The new SR system may support efficient radiological
      reporting for initial diagnosis and follow-up for AAA. Perceived advantages of
      our SR platform are ease of use, which may lead to more accurate decision
      support. The new system is open to communicate not only with clinical partners
      but also with Radiology Information and Hospital Information Systems.

PMID- 23956063
TI  - Allen's rule revisited: temperature influences bone elongation during a critical
      period of postnatal development.
AB  - Limbs of animals raised at warm ambient temperature are significantly and
      permanently longer than those of siblings housed in the cold. These highly
      reproducible lab results closely parallel the ecogeographical tenet described by
      Allen's extremity size rule, which states that appendage length correlates with
      temperature and latitude. It is unclear what mechanisms underlie these
      differences and in what pattern they emerge, since the morphology is
      traditionally thought to reflect naturally selected genomic adaptations for
      thermoregulation. This study tests the a posteriori hypothesis that adult
      extremity length is subject to substantial modification by temperature during a
      brief but critical period of early postnatal development. Weanling mice (N = 28)
      were divided into three groups and housed at 7 degrees C, 21 degrees C, or 27
      degrees C for eight weeks. Tail lengths and body mass were measured weekly. Mass
      did not differ at any age. Analysis of tail elongation curves revealed two
      distinct phases: an initial period of rapid temperature-sensitive growth in which
      elongation rate was directly impacted by temperature; and a second phase of
      continued growth in which rates were identical among groups. Comparable growth
      reactions occur in response to other environmental variables such as exercise,
      suggesting that the skeleton is most responsive to external stimuli during a
      window of heightened sensitivity when growth occurs most rapidly. Knowledge of
      the timing and degree to which growth plasticity permits mammals to immediately
      adjust to novel temperature conditions will be important for analyzing skeletal
      variation in fluctuating climates, particularly for assessing factors that may
      accelerate skeletal evolution at temperature extremes.

PMID- 23956064
TI  - Design and preparation of molybdenum-dinitrogen complexes with
      ferrocenyldiphosphine and pentamethylcyclopentadienyl moieties as auxiliary
      ligands.
AB  - Fix me! Molybdenum-dinitrogen complexes containing ferrocenyldiphosphine and
      pentamethylcyclopentadienyl moieties as auxiliary ligands have been designed,
      prepared, and characterized. The ferrocenyldiphosphine works as a unique ligand
      to inhibit dissociation of dinitrogen, as well as to make the coordinated
      molecular dinitrogen reactive toward electrophiles. 

PMID- 23956065
TI  - Development of a gamma-alumina- nanoparticle-functionalized porous polymer
      monolith for the enrichment of Sudan dyes in red wine samples.
AB  - Monolithic materials were synthesized in capillaries by in situ polymerization
      with N-isopropylacrylamide, glycidyl methacrylate, and ethylene dimethacrylate as
      the monomers, and methanol and PEG as the porogens. With gamma-alumina
      nanoparticles attached to the surface of the porous monolithic column via epoxide
      groups, a novel polymer monolith microextraction (PMME) material was prepared
      with a good mechanical stability and a high extraction capacity. SEM and X-ray
      photoelectron spectroscopy were employed to characterize the modified monolithic
      column, demonstrating that gamma-alumina nanoparticles were effectively
      functionalized onto the monolithic column. In addition, a new method was
      developed for the analysis of Sudan I-IV dyes using PMME coupled with HPLC. In
      order to obtain the optimum extraction efficiency, the PMME conditions including
      desorption solvent type, sample pH, sample volume, sample flow rate, and eluent
      flow rate were investigated. Under the optimum conditions, we obtained acceptable
      linearities, low LODs, and good intra- and interday RDSs. When applied to the
      determination of Sudan I-IV dyes in red wine samples, satisfactory recoveries
      were obtained in the range of 84.0-115.9%. 

PMID- 23956066
TI  - Ultrasound-guided intratumoral indigo carmine injection for intraoperative,
      surgeon-performed tumor localization.
AB  - BACKGROUND: The purpose of this study was to evaluate the feasibility of
      ultrasound-guided intratumoral indigo carmine injections for intraoperative
      localization of small head and neck tumors and to introduce our surgeon-performed
      technique. METHODS: In total, 23 patients who had tumors <=1.5 cm that were not
      palpable by 2 head and neck surgeons were enrolled in this prospective study.
      RESULTS: Ultrasound-guided intratumoral indigo carmine injections successfully
      targeted tumors in 22 patients (95.7%). The mean preinjection target tumor size
      was 0.8 cm. After an average injection of 0.7 mL indigo carmine, the mean target
      tumor size increased to 1.0 cm, which enhanced visual demarcation because of the
      increased tumor size. In these patients, we successfully and uneventfully
      resected the target tumors with ultrasound-guided intratumoral indigo carmine
      injection assistance. CONCLUSION: Ultrasound-guided intratumoral indigo carmine
      injections were technically feasible as an intraoperative procedure and were
      performed safely by a head and neck surgeon to facilitate localization of small
      head and neck tumors, even in revision cases.

PMID- 23956067
TI  - Initial testing (stage 1) of the Polo-like kinase inhibitor volasertib (BI 6727),
      by the Pediatric Preclinical Testing Program.
AB  - BACKGROUND: Volasertib (BI 6727) is a potent inhibitor of Polo-like kinase 1
      (Plk1), that is overexpressed in several childhood cancers and cell lines.
      Because of its novel mechanism of action, volasertib was evaluated through the
      PPTP. PROCEDURES: Volasertib was tested against the PPTP in vitro cell line panel
      at concentrations from 0.1 nM to 1.0 MUM and against the PPTP in vivo xenograft
      panels administered IV at a dose of 30 mg/kg (solid tumors) or 15 mg/kg (ALL
      models) using a q7dx3 schedule. RESULTS: In vitro volasertib demonstrated
      cytotoxic activity, with a median relative IC50 value of 14.1 nM, (range 6.0-135
      nM). Volasertib induced significant differences in EFS in 19 of 32 (59%) of the
      evaluable solid tumor xenografts and in 2 of 4 (50%) of the evaluable ALL
      xenografts. Volasertib induced tumor growth inhibition meeting criteria for
      intermediate EFS T/C (>2) activity in 11 of 30 (37%) evaluable solid tumor
      xenografts, including neuroblastoma (4 of 6) and glioblastoma (2 of 3) panels,
      and 2 of 4 ALL models. Objective responses (CR's) were observed for 4 of 32 solid
      tumor (two neuroblastoma, one glioblastoma, and one rhabdomyosarcoma) and one of
      four ALL xenografts. CONCLUSIONS: Volasertib shows potent in vitro activity
      against the PPTP cell lines with no histotype selectivity. In vivo, volasertib
      induced regressions in several xenograft models. However, pharmacokinetic data
      suggest that mice tolerate higher systemic exposure to volasertib than humans,
      suggesting that the current results may over-estimate potential clinical efficacy
      against the childhood cancers studied.

PMID- 23956069
TI  - Diapause development in early and late emerging phenotypes of Delia floralis.
AB  - The turnip fly, Delia floralis Fallen (Diptera: Anthomyiidae) is an important
      insect pest of brassica vegetable crops in the holarctic region. Different
      populations have strongly varying temperature requirements for fly emergence, a
      challenge for accurate prediction of activity. This study focused on diapause
      development in one early and one late emerging phenotype. The physiological state
      after various treatments was deduced from emergence data. Our results showed a
      slow diapause progression at chilling conditions for both populations and
      diapause ended about 7 months after pupae were formed for the early population.
      For the late population held at 4 degrees C diapause did not end, no matter how
      long the duration of chilling. These pupae required a period with elevated
      temperatures above 6 degrees C to continue development. At constant non-chilling
      conditions (18 degrees C) from the time pupae were formed both populations
      completed diapause most rapidly. These results indicate that chilling delayed,
      rather than accelerated development and was not a prerequisite for diapause
      development. For post-diapause, results indicated a linear relationship between
      rate of development and temperature within the range of 6-18 degrees C and a
      theoretical base temperature for development of about 2 degrees C for both
      populations. In conclusion, D. floralis pupae are in diapause throughout a long
      winter period, and delayed emergence of the late population appears to be caused
      by prolonged diapause regulated by a developmental temperature threshold. The
      study has added information on the biology of turnip fly populations, a
      prerequisite for improved pest control. 

PMID- 23956068
TI  - Tier-1 assays for assessing the toxicity of insecticidal proteins produced by
      genetically engineered plants to non-target arthropods.
AB  - In assessing an insect-resistant genetically engineered (IRGE) crop before its
      commercialization, researchers normally use so-called "Tier-1 assays" as the
      initial step to determine the effects of the crop on non-target organisms. In
      these tests, the insecticidal proteins (IPs) produced by the IRGEs are added to
      the diets of test organisms in the laboratory. Test organisms in such assays can
      be directly exposed to much higher concentrations of the test IPs than they would
      encounter in the field. The results of Tier-1 assays are thus more conservative
      than those generated in studies in which the organisms are exposed to the IPs by
      feeding on IRGE plant tissue or in the case of predators or parasites, by feeding
      on invertebrate prey or hosts that have fed on IRGE plant tissue. In this report,
      we consider three important factors that must be considered in Tier-1 assays: (i)
      methods for delivery of the IP to the test organisms; (ii) the need for and
      selection of compounds used as positive controls; and (iii) methods for
      monitoring the concentration, stability and bioactivity of the IP during the
      assay. We also analyze the existing data from Tier-1 assays regarding the
      toxicity of Bt Cry proteins to non-target arthropod species. The data indicate
      that the widely used Bt proteins have no direct toxicity to non-target organisms.

PMID- 23956070
TI  - Foliar persistence and residual activity of methoxyfenozide against beet armyworm
      (Lepidoptera: Noctuidae).
AB  - A greenhouse study was conducted to investigate the persistence of
      methoxyfenozide in pepper (Capsicum annuum L.) foliage. An aqueous suspension of
      methoxyfenozide was sprayed on pepper plants at concentrations of 72 and 144 mg
      of active ingredient (a.i.)/L. Foliage was collected at different intervals of
      time (0, 3, 5, 10, 20, 30, 40, and 50 days) after the treatment, and the
      methoxyfenozide residue was measured by high-performance liquid chromatography.
      The foliage was also used in bioassays to determine the residual toxicity on and
      the consumption rate of the third-instar larvae of the beet armyworm, Spodoptera
      exigua (Hubner) (Lepidoptera: Noctuidae). The methoxyfenozide concentrations
      observed after 50 days had decreased to 19 and 69 MUg/g per sample, corresponding
      to a loss of 61% and 28% from the application concentrations of 72 and 144 mg
      a.i./L, respectively. When fitting a first-order kinetics degradation model, the
      half-life (DT50 ) of this compound was 76 days. Both application concentrations
      of methoxyfenozide caused a high mortality rate (>=97%) when the larvae were fed
      the pepper foliage collected at all of the time intervals. Lastly, at all of the
      time points, the consumption rate by the larvae was reduced to between 57% and
      92% for both concentrations that were bioassayed. Our results indicate that,
      under the present greenhouse conditions, the degradation of methoxyfenozide was
      slower than that reported by other authors and that its residues were highly
      toxic to S. exigua larvae. The implications of these results for the management
      programs of this pest are discussed. 

PMID- 23956072
TI  - Highly efficient, water-soluble polarizing agents for dynamic nuclear
      polarization at high frequency.

PMID- 23956071
TI  - Hypoxia induces adipocyte differentiation of adipose-derived stem cells by
      triggering reactive oxygen species generation.
AB  - Generation of reactive oxygen species (ROS) by NADPH oxidase 4 (Nox4) induces the
      proliferation and migration of adipose-derived stem cells (ASCs). However, the
      functional role of mitochondrial ROS (mtROS) generation in ASCs is unknown.
      Therefore, we have investigated whether hypoxia induces the differentiation of
      ASCs via ROS generation. We also have tried to identify the cellular mechanisms
      of ROS generation underlying adipocyte differentiation. Hypoxia (2%) and ROS
      generators, such as antimycin and rotenone, induced adipocyte differentiation,
      which was attenuated by an ROS scavenger. Although Nox4 generates ROS and
      regulates proliferation of ASCs, Nox4 inhibition or Nox4 silencing did not
      inhibit adipocyte differentiation; indeed fluorescence intensity of mito-SOX
      increased in hypoxia, and treatment with mito-CP, a mtROS scavenger,
      significantly reduced hypoxia-induced adipocyte differentiation. Phosphorylation
      of Akt and mTOR was induced by hypoxia, while inhibition of these molecules
      prevented adipocyte differentiation. Thus hypoxia induces adipocyte
      differentiation by mtROS generation, and the PI3K/Akt/mTOR pathway is involved. 

PMID- 23956073
TI  - Intracellular NHX-type cation/H+ antiporters in plants.

PMID- 23956074
TI  - AtECB1/MRL7, a thioredoxin-like fold protein with disulfide reductase activity,
      regulates chloroplast gene expression and chloroplast biogenesis in Arabidopsis
      thaliana.
AB  - Plastid-encoded RNA polymerase (PEP) is closely associated with numerous factors
      to form PEP complex for plastid gene expression and chloroplast development.
      However, it is not clear how PEP complex are regulated in chloroplast. Here, one
      thioredoxin-like fold protein, Arabidopsis early chloroplast biogenesis 1
      (AtECB1), an allele of MRL7, was identified to regulate PEP function and
      chloroplast biogenesis. The knockout lines for AtECB1 displayed albino phenotype
      and impaired chloroplast development. The transcripts of PEP-dependent plastid
      genes were barely detected, suggesting that the PEP activity is almost lost in
      atecb1-1. Although AtECB1 was not identified in PEP complex, a yeast two-hybrid
      assay and pull-down experiments demonstrated that it can interact with Trx Z and
      FSD3, two intrinsic subunits of PEP complex, respectively. This indicates that
      AtECB1 may play a regulatory role for PEP-dependent plastid gene expression
      through these two subunits. AtECB1 contains a betaalphabetaalphabetabetaalpha
      structure in the thioredoxin-like fold domain and lacks the typical C-X-X-C
      active site motif. Insulin assay demonstrated that AtECB1 harbors disulfide
      reductase activity in vitro using the purified recombinant AtECB1 protein. This
      showed that this thioredoxin-like fold protein, AtECB1 also has the thioredoxin
      activity. AtECB1 may play a role in thioredoxin signaling to regulate plastid
      gene expression and chloroplast development. 

PMID- 23956075
TI  - The antiinflammatory mechanism of Igongsan in mouse peritoneal macrophages via
      suppression of NF-kappaB/Caspase-1 activation.
AB  - Igongsan (IGS), which is an herbal prescription composed of five different herbs,
      Ginseng Radix (root of Panax ginseng, Araliaceae), Atractylodis Rhizoma Alba
      (rhizome of Atractylodes Macrocephala, Compositae), Poria Sclerotium (sclerotium
      of Poria cocos, Polyporaceae), Glycyrrhizae Radix et Rhizoma (root and rhizome of
      Glycyrrhiza uralensis, Leguminosae), and Citri Unshius Pericarpium (Peel of
      Citrus unshiu, Rutaceae), has been traditionally used in Korea to treat a variety
      of inflammatory diseases. In this study, we investigated to elucidate the
      mechanism responsible for IGS's antiinflammatory effect in mouse peritoneal
      macrophages. The findings demonstrate that IGS inhibited the production of
      inflammatory cytokine and prostaglandins E2 . IGS inhibited the enhanced levels
      of cyclooxygenase-2 and inducible NO synthase caused by lipopolysaccharide (LPS).
      Additionally, it was shown that the antiinflammatory effect of IGS is through
      regulating the activation of nuclear factor-kappa B and caspase-1 in LPS
      stimulated mouse peritoneal macrophages. These results provide novel insights
      into the pharmacological actions of IGS as a potential candidate for development
      of new drugs to treat inflammatory diseases. DISCUSSION AND CONCLUSION: These
      results provide novel insights into the pharmacological actions of IGS as a
      potential candidate for development of new drugs to treat inflammatory diseases.

PMID- 23956076
TI  - Preparation and application of hollow molecularly imprinted polymers with a super
      high selectivity to the template protein.
AB  - Protein-imprinted polymers with hollow cores that have a super-high imprinting
      factor were prepared by etching the core of the surface-imprinted polymers that
      used silica particles as the support. Lysozyme as template was modified onto the
      surface of silica particles by a covalent method, and after polymerization and
      the removal of template molecules, channels through the polymer layer were
      formed, which allowed a single-protein molecule to come into the hollow core and
      attach to the binding sites inside the polymer layer. The adsorption experiments
      demonstrated that the hollow imprinted polymers had an extremely high binding
      capacity and selectivity, and thus a super-high imprinting factor was obtained.
      The as-prepared imprinted polymers were used to separate the template lysozyme
      from egg white successfully, indicating its high selectivity and potential
      application in the field of separation of protein from real samples. 

PMID- 23956077
TI  - No benefit in staging fluorodeoxyglucose-positron emission tomography in
      clinically node-negative head and neck cutaneous melanoma.
AB  - BACKGROUND: Fluorodeoxyglucose-positron emission tomography (FDG-PET) has a high
      sensitivity for detecting metastasis from melanoma, but its application in early
      stage melanomas is questionable. The purpose of this study was to determine if
      positron emission tomography (PET) is beneficial in staging of clinically node
      negative (cN0) head and neck melanoma. METHODS: After institutional review board
      approval, patients with head and neck melanoma treated at 2 cancer centers
      (between 2000 and 2010) were identified using International Classification of
      Disease (ICD)-9 codes. A retrospective medical chart review of cN0 patients was
      performed for the treatment course and outcomes. RESULTS: A total of 165 patients
      were treated; of these, 106 were node negative. FDG-PET was included in initial
      staging of 47 cN0 patients. None had true distant metastasis detected on PET. The
      imaging also failed to detect nodal metastasis in 2 patients who had disease on
      lymphatic sampling. CONCLUSION: FDG-PET did not alter the initial staging or
      treatment in patients with cN0 head and neck melanoma. Therefore, its routine use
      for staging is not warranted.

PMID- 23956078
TI  - Targets, structures, and recent approaches in malignant melanoma chemotherapy.
AB  - Malignant metastatic melanoma is one of the oncologic diseases with the worst
      clinical prognosis, due primarily to resistance phenomena against
      chemotherapeutic agents in current use. However, over the last few years,
      characterization of the molecular mechanisms involved in the development and
      progression of the disease has contributed to elucidation of the main pathways by
      which tissue invasion and metastasis can occur. More importantly, the
      identification of abnormalities in signaling cascades in melanoma cells has
      facilitated new therapeutic approaches against malignant melanoma through the
      design of highly potent and selective drugs with low associated toxicity.
      Ultimately, recognition of the restricted applicability of new chemotherapies in
      certain genetic contexts has led to significant improvements in the results of
      clinical trials, anticipating the existing need for investment in personalized
      therapies, and taking into account the molecular alterations observed in tumors.
      Although significant advances have been made in terms of extending the median
      overall survival rate and improving the quality of life for patients, the
      mechanisms that compromise in vivo drug efficacy remain poorly understood,
      particularly those concerning therapeutic resistance phenomena. This review
      summarizes recently validated targets from the perspective of the medicinal
      chemistry carried out in the design of the most promising structures. 

PMID- 23956080
TI  - Dynamic functional integration of distinct neural empathy systems.
AB  - Recent evidence points to two separate systems for empathy: a vicarious sharing
      emotional system that supports our ability to share emotions and mental states
      and a cognitive system that involves cognitive understanding of the perspective
      of others. Several recent models offer new evidence regarding the brain regions
      involved in these systems, but no study till date has examined how regions within
      each system dynamically interact. The study by Raz et al. in this issue of
      Social, Cognitive, & Affective Neuroscience is among the first to use a novel
      approach of functional magnetic resonance imaging analysis of fluctuations in
      network cohesion while an individual is experiencing empathy. Their results
      substantiate the approach positing two empathy mechanisms and, more broadly,
      demonstrate how dynamic analysis of emotions can further our understanding of
      social behavior. 

PMID- 23956079
TI  - The effect of bacterial challenge on ferritin regulation in the yellow fever
      mosquito, Aedes aegypti.
AB  - Secreted ferritin is the major iron storage and transport protein in insects.
      Here, we characterize the message and protein expression profiles of yellow fever
      mosquito (Aedes aegypti) ferritin heavy chain homologue (HCH) and light chain
      homologue (LCH) subunits in response to iron and bacterial challenge. In vivo
      experiments demonstrated tissue-specific regulation of HCH and LCH expression
      over time post-blood meal (PBM). Transcriptional regulation of HCH and LCH was
      treatment specific, with differences in regulation for naive versus mosquitoes
      challenged with heat-killed bacteria (HKB). Translational regulation by iron
      regulatory protein (IRP) binding activity for the iron-responsive element (IRE)
      was tissue-specific and time-dependent PBM. However, mosquitoes challenged with
      HKB showed little change in IRP/IRE binding activity compared to naive animals.
      The changes in ferritin regulation and expression in vivo were confirmed with in
      vitro studies. We challenged mosquitoes with HKB followed by a blood meal to
      determine the effects on ferritin expression, and demonstrate a synergistic, time
      dependent regulation of expression for HCH and LCH. 

PMID- 23956082
TI  - [Expression and regulation of the SOST gene].
AB  - Sclerostin(SOST), mainly expressed in osteocytes, is a negative regulator of bone
      formation. Hormones PTH and E2 inhibit the expression of the SOST gene.
      Transcription factors Osterix, Runx2, and Mef2c promote the SOST expression,
      while Sirt1 negatively regulates the SOST expression. In addition, the expression
      of the SOST gene is regulated by epigenetic mechanisms, such as DNA methylation
      and microRNA. Mutations in the SOST gene, which cause sclerosteosis and Van
      Buchem diseases, are associated with osteoporosis. Wnt and BMP are two important
      signaling pathways in bone metabolic regulation. SOST can regulate osteoblastic
      differentiation and bone formation by binding type I/II receptors and co-receptor
      LRP5/6 to inhibit BMP and Wnt signaling pathways. Suppression of SOST provides a
      new approach for osteoporosis treatment. This review covers the structure,
      function and expression regulation of the SOST gene, human disease association,
      mechanism in the regulation of bone metabolism and prospect in clinical
      application. 

PMID- 23956083
TI  - [Research progress in hypoxanthine-guanine phosphoribosyltrans-ferase].
AB  - Hypoxanthine-guanine phosphoribosyltransferase (HPRT) is a cytoplasmic enzyme
      which is widely distributed in the body. It not only involves in the purine
      salvage pathway, but also relates to the metabolism of purine analogues drugs. It
      is a critical transferase regulating the pharmacological effects and toxicity of
      purine analogues drugs. The mutations of the gene for HPRT, which influence its
      activity, may cause metabolic diseases with different clinical symptoms, and
      influence the metabolism of purine analogues. The HPRT gene, also a housekeeping
      gene, can serve diagnostic markers for many disorders. This paper reviews the
      recent progresses on HPRT researches in promoting the individual treatment of
      analogues drugs and the development of new drugs and improving the diagnosis and
      therapy of inherited metabolic disease caused by HPRT mutations. 

PMID- 23956081
TI  - How affective information from faces and scenes interacts in the brain.
AB  - Facial expression perception can be influenced by the natural visual context in
      which the face is perceived. We performed an fMRI experiment presenting
      participants with fearful or neutral faces against threatening or neutral
      background scenes. Triangles and scrambled scenes served as control stimuli. The
      results showed that the valence of the background influences face selective
      activity in the right anterior parahippocampal place area (PPA) and subgenual
      anterior cingulate cortex (sgACC) with higher activation for neutral backgrounds
      compared to threatening backgrounds (controlled for isolated background effects)
      and that this effect correlated with trait empathy in the sgACC. In addition, the
      left fusiform gyrus (FG) responds to the affective congruence between face and
      background scene. The results show that valence of the background modulates face
      processing and support the hypothesis that empathic processing in sgACC is
      inhibited when affective information is present in the background. In addition,
      the findings reveal a pattern of complex scene perception showing a gradient of
      functional specialization along the posterior-anterior axis: from sensitivity to
      the affective content of scenes (extrastriate body area: EBA and posterior PPA),
      over scene emotion-face emotion interaction (left FG) via category-scene
      interaction (anterior PPA) to scene-category-personality interaction (sgACC). 

PMID- 23956084
TI  - [Studies on the transcriptomes of non-model organisms].
AB  - The transcriptome represents the whole complement of RNA transcripts in cells or
      tissues and reflects the expressed genes at various life stages, tissue types,
      physiological states, and environmental conditions. Transcriptome analysis
      provides a comprehensive understanding of gene expression and its regulation. Non
      model organism has many interesting traits of which model organisms lack, and the
      study of its transcriptome has great significance in solving the questions of
      genetic evolution, genetic breeding, ecology and so on. Because of absence of
      reference genome information, and traditional transcriptome research methods
      which are complicated to operate, long experimental period and costly, slow
      progress has been made in the research of non-model organism transcriptome.
      Fortunately, RNA sequencing (RNA-seq), the next-generation sequencing technology,
      has completely changed the way of transcriptome study, becoming an advanced
      technology on the investigation of non-model organism transcriptome. In this
      paper, we give a summary of the non-model organism transcriptome research using
      RNA-seq in recent years and briefly describe its general flow and principles from
      aspects of sample preparation, high throughput DNA sequencing, and bioinformatics
      analysis. Finally, questions that are still open and awaiting further research
      are also discussed. 

PMID- 23956085
TI  - [Transcription factors in resistance against pathogen Botrytis cinerea in
      Arabidopsis].
AB  - A large number of defense genes are activated in plants when responding to
      pathogen infection. Furthermore, transcription factors are suggested to play
      important roles in regulating huge defense network in plants. The necrotrophic
      fungus Botrytis cinerea is one of the most destructive pathogens which could
      result in massive economic losses in the agriculture. Our review summarized the
      study results of members from transcription factor ERF, WRKY and MYB families
      which function in resistance of Botrytis cinerea in Arabidopsis thaliana. The
      transcription factors come into more elaborate regulation network through
      interacting with target genes at mRNA or protein levels aiming at activating
      expression of defense genes which lead to resistance against the fungus. Some
      transcriptional factors were discovered to be the main nodes and regulators in
      different phytohormones crosstalk, illustrating and connecting the molecular
      mechanisms of plants against different types of pathogens. Study on the
      transcription factor mentioned above, provides us clues for the study of other
      plant pathogen defense mechanism. Further understanding of disease mechanisms
      will help researchers to utilize the resis-tance genes in crop improvement and
      protection practice. 

PMID- 23956086
TI  - [The principle of dRNA-seq and its applications in prokaryotic tran-scriptome
      analyses].
AB  - The genomic and transcriptomic studies have been greatly accelerated by the next
      generation sequencing technology. Currently, there are two main methods in
      transcriptomic studies, namely, Tiling microarray and RNA-seq. Comparatively,
      because of its overwhelming superiority in transcript coverage and resolution, as
      well as decrease of costs, RNA-seq has been employed in transcriptome analyses by
      an increasing number of research institutes. According to the mRNA enrichment or
      rRNA depletion methods, RNA-seq can be performed in six ways. Among them, dRNA
      seq can descriminate the original transcripts from the processed RNAs based on a
      differential exonuclease treatment. This kind of method has been broadly applied
      in studies of prokaryotic transcriptional start sites, small regulatory RNAs,
      promoters and operons, etc. Here, we reviewed the detailed principle and
      technical process of dRNA-seq and its applications in prokaryotic transcriptome
      analyses. Besides, we also summarized the advantages and limitations of dRNA-seq
      at present stage, and then gave our perspective of its future development and
      potential applications, expecting to present useful references for civil
      researchers in related fields. 

PMID- 23956087
TI  - [Association between six single nucleotide polymorphisms of EGLN1 gene and
      adaptation to high-altitude hypoxia].
AB  - To investigate the association between SNPs located in 5'UTR and intron of prolyl
      hydroxylase 2 (EGLN1 or PHD2) and adaptation to high-altitude hypoxia, the SNPs
      (rs2066140, rs2808584, rs2491405, rs2486741, rs2486734 and rs21533646) of EGLN1
      gene were genotyped using Sequenom MassArray genotyping system in 152 unrelated
      healthy Tibetan individuals (3 650 m altitude) and 192 Han (5 00 m altitude), and
      the haplotypes of these SNPs were constructed and analyzed. Our results showed
      all the homozygous genotypes of six SNPs loci were significantly different
      between the two groups (P<0.05). The frequencies of haplotypes G-G (rs2066140 and
      rs2808584) and G-C (rs2486741 and rs2486734) of high-altitude group were
      significantly different from low-altitude group (P<0.05). In addition, the
      frequencies of haplotypes C-A (rs2066140 and rs2808584) and C-T (rs2486741 and
      rs2486734) of high-altitude group were significantly lower than those in low
      altitude group (P<0.05). Our results indicate that the polymorphism of homozygous
      genotype in six SNPs and their haplotypes were associated with adaptation to high
      altitude hypoxia. 

PMID- 23956088
TI  - [Insertion efficiency of Tgf2 transposon in the genome of Megalo-brama
      amblycephala].
AB  - To study insertion efficiency of goldfish Tgf2 transposon in the genome of
      Megalobrama amblycephala, we built Tgf2-Mlyz2-RFP donor plasmid with goldfish
      Tgf2 transposon left and right arms, and then co-injected with goldfish Tgf2
      transposase mRNA into the 1-2 cell stage fertilized eggs of M. amblycephala. In
      30 d- and 180 d-stage larval, RFP fluorescence can be observed in back and side
      muscle of the fish. The rate of RFP fluorescence expression was 48.1%. In adult
      fish, PCR results demonstrated that integration efficiency of goldfish Tgf2
      transposition system was 31.5% in M. am-blycephala genome. RT-PCR analysis showed
      that RFP RNAs were highly transcribed among all the 12 tissues in three
      transgenic fishes, while it could be highly detected only in muscle, skin, and
      kidney in another two individuals. Our results suggested that RFP expression in
      tissues vaied among different M. amblycephala. By means of the inverse PCR, the
      copy numbers of Tgf2 transposon were at least 2 in transgenic M. amblycephala.
      The average copy number of each fish was about 5. Over 50% of flanking sequences
      at the insertion site have homologous sequence in other vertebrate species. Our
      data suggest that goldfish Tgf2 transposon can efficiently mediate gene insertion
      in M. amblycephala, which could been used in transgene and gene trap in M.
      amblycephala. 

PMID- 23956089
TI  - [Analysis on breeding potential of eight synthetic populations to improve a
      Chinese maize hybrid Zhengdan 958].
AB  - Maize (Zea mays L.) populations are potential sources of favorable alleles absent
      in parental inbred lines to improve elite hybrids. The maize hybrid Zhengdan 958
      has been hampered by the lack of favorable new alleles for improving yield and
      commodity quality. In the present study, 16 testcrosses made by using eight
      synthetic populations as the donors and the two parental lines of Zhengdan 958 as
      the receptors were evaluated in 2009 and 2010 at Shunyi, Beijing and Xinxiang,
      Henan Province for grain yield and test weight. Four genetic parameters were used
      to determine the breeding potential of eight synthetic populations as the donors
      to improve the target hybrid. Several synthetic populations were identified as
      the potential sources of favorable alleles absent in the target hybrid for each
      trait evaluated. The two most promising germplasms, WBMC-4 and Shanxi Syn3, had
      the potential for simultaneously improving grain yield and test weight of the
      target hybrid, which could be used to improve the parental lines Zheng 58 and
      Chang 7-2, respectively, and further broaden the germplasm base of Chinese
      heterotic groups PA and Sipingtou. 

PMID- 23956090
TI  - [Transposon expression and potential effects on gene regulation of Brassica rapa
      and B. oleracea genomes].
AB  - Transposons or transposable elements (TEs) are ubiquitous and most abundant DNA
      components in higher eukaryotes. Recent sequencing of the Brassica rapa and B.
      oleracea genomes revealed that the amplification of TEs is one of the main
      factors inducing the difference in genome size. However, the expressions of TEs
      and the TE effects on gene regulation and functions of these two Brassica diploid
      species were unclear. Here, we analyzed the RNA sequencing data of leaves, roots,
      and stems from B. rapa and B. oleracea. Our data showed that overall TEs in
      either genome expressed at very low levels, and the expression levels of
      different TE categories and families varied among different organs. Moreover,
      even for the same TE category or family, the expression activities were distinct
      between the two Brassica diploids. Forty-one and nine LTR retrotransposons with
      the transcripts that read into their adjacent sequences have the distances
      shorter than 2 kb and 100 bp compared to the downstream genes. These LTR
      retrotransposon readout transcriptions may produce sense or antisense transcripts
      of nearby genes, with the effects on activating or silencing corresponding genes.
      Meanwhile, intact LTRs were detected at stronger readout activities than solo
      LTRs. Of the TEs inserted into genes, the frequencies were ob-served at a higher
      level in B. rapa than in B. oleracea. In addition, DNA transposons were prone to
      insert or retain in the intronic regions of genes in either Brassica genomes.
      These results revealed that the TEs may have potential effects on regulating
      protein coding genes. 

PMID- 23956091
TI  - [Antimicrobial activities of ant Ponericin W1 against plant pathogens in vitro
      and the disease resistance in its transgenic Arabidopsis].
AB  - The antimicrobial peptides (AMPs) exhibit a broad antimicrobial spectrum. The
      application of AMPs from non-plant organisms attracts considerable attention in
      plant disease resistance engineering. Ponericin W1, isolated from the venom of
      ant (Pachycondyla goeldii), shows antimicrobial activities against Gram-positive
      bacteria, Gram-negative bacteria and the budding yeast (Saccharomyces
      cerevisiae); however, it is not clear whether Ponericin W1 is effective against
      plant pathogens. The results of this study indicated synthesized Ponericin W1
      inhibited mycelial growth of Magnaporthe oryzae and Botrytis cinerea, as well as
      hyphal growth and spore production of Fusarium graminearum. Besides, Ponericin W1
      exhibited antibacterial activities against Pseudomonas syringae pv. tomato and
      Xanthomonas oryzae pv. oryzae. After codon optimization, Ponericin W1 gene was
      constructed into plant expression vector, and transformed into Arabidopsis
      thaliana by floral dip method. The Ponericin W1 was located in intercellular
      space of the transgenic plants as expected. Compared with the wild-type plants,
      there were ungerminated spores and less hyphal, conidia on the leaves of
      transgenic plants after innoculation with the powdery mildew fungus Golovinomyces
      cichoracearum. After innoculation with the pathogenic bac-terium Pseudomonas
      syringae pv. tomato, the baceria in the leaves of transgenic plants was
      significantly less than the wild-type plants, indicating that the transgenic
      plants displayed enhanced disease resistance to pathogens. These results
      demonstrate a potential use of Ponericin W1 in genetic engineering for broad
      spectrum plant disease resistance. 

PMID- 23956092
TI  - [Cnb1 involved in cytokinesis in Schizosaccharomyces pombe].
AB  - Serine/Threonine-specific calcineurin (CN) is highly conserved in eukaryotes,
      which plays an important role in transcriptional regulation. In
      Schizosaccharomyces pombe, CN exists as a heterodimer composed by catalytic
      subunit Ppb1 and regulatory subunit Cnb1. Deletion of cnb1+ reduced the growth
      rate of cells, and caused a chained phenotype, and had delay in cytokinesis. In
      cytokinesis, Cnb1 could form CN complex with Ppb1 and could colocalize and
      constrict with the contractile ring at division plane. Tubulin could cross the
      septum in cnb1Delta strain, suggesting that the septum is not fully matured.
      These results suggest Cnb1 might be involved in maturation of septum. The signals
      of septins in cnb1Delta strain were also analyzed. Septins include Spn1, Spn2,
      Spn3, and Spn4. Septins help to guide hydrolytic enzymes for septum degrada-tion.
      Eighty percent of cnb1Delta cells lacked the signals of Spn2 or Spn3 at septum,
      and twenty percent of cnb1Delta cells lacked the signals of Spn1 or Spn4 at
      septum. The reduction of the septin signals was not due to impaired transcription
      of septins, since the protein levels of septins in the cnb1Delta cells were not
      decreased. These results imply that Cnb1 might regulate the stability of septin
      ring in a transcription-independent manner. In general, our study showed that
      Cnb1 contributes to the maturation of septum and the stability of septin ring and
      is important in the cytokinesis. 

PMID- 23956093
TI  - [Exploration on human blood type case in teaching practice of genetics].
AB  - Blood type, which harbors abundant genetics meaning, is one of the most common
      phenotypes in human life. With the development of science and technology, its
      significance is unceasingly updated and new finding is increasingly emerging,
      which constantly attracts people to decipher the heredity mechanism of blood
      type. In addition to four main associated contents, i.e., Mendelian inheritance,
      genetic linkage, gene mutations, and chromosome abnormalities, the blood type
      case also covers many other aspects of the genetics knowledge. Based on the
      genetic knowledge context, we can interest the students and improve the teaching
      output in genetic teaching practice by combining with explaining ABO blood type
      case and heredity mechanism, expanding leucocyte groups, and introducing
      infrequent blood type such as Bombay blood, Rh and MN. By carrying out the
      related experimental teaching, we could drive the student to integrate theory
      with practice. In genetic experimental teaching, 80% of the students chose this
      optional experiment, molecular identification of ABO blood type, and it greatly
      interested them. Using appropriate blood type case in teaching related knowledge,
      organizing PPT exhi-bition and the debating discussion activities, it could
      provide opportunities for student to propose their own opinions, guide the
      student to thinking deeply, and develop their abilities to analyze and solve
      problem. Afterwards, students will gain in-depth comprehension about the
      fundamental knowledge of genetics. 

PMID- 23956094
TI  - Innovative educational approaches to engage and empower the adolescent and young
      adult childhood cancer survivor.
AB  - There is a long history of challenges when delivering care to adolescents and
      young adults (AYA) with chronic healthcare needs. For the AYA survivor of
      childhood cancer, these challenges may include complex medical care, a multitude
      of psychosocial issues and systemic barriers to care. Educating this population
      is critical as they assume age-appropriate responsibility for their health and
      become active partners in their survivorship care. We present our regional
      experience with educational programming directed to AYA survivors of childhood
      cancer featuring an innovative approach to engaging and empowering this
      population.

PMID- 23956095
TI  - Changes in glutathione redox cycle during diapause determination and termination
      in the bivoltine silkworm, Bombyx mori.
AB  - To explore whether glutathione regulates diapause determination and termination
      in the bivoltine silkworm Bombyx mori, we monitored the changes in glutathione
      redox cycle in the ovary of both diapause- and nondiapause-egg producers, as well
      as those in diapause eggs incubated at different temperatures. The activity of
      thioredoxin reductase (TrxR) was detected in ovaries but not in eggs, while
      neither ovaries nor eggs showed activity of glutathione peroxidase. A lower
      reduced glutathione/oxidized glutathione (GSH/GSSG) ratio was observed in the
      ovary of diapause-egg producers, due to weaker reduction of oxidized glutathione
      (GSSG) to the reduced glutathione (GSH) catalyzed by glutathione reductase (GR)
      and TrxR. This indicates an oxidative shift in the glutathione redox cycle during
      diapause determination. Compared with the 25 degrees C-treated diapause eggs, the
      5 degrees C-treated diapause eggs showed lower GSH/GSSG ratio, a result of
      stronger oxidation of GSH catalyzed by thioredoxin peroxidase and weaker
      reduction of GSSG catalyzed by GR. Our study demonstrated the important
      regulatory role of glutathione in diapause determination and termination of the
      bivoltine silkworm.

PMID- 23956096
TI  - Tolerance to individual and joint effects of arsenic and Bacillus thuringiensis
      subsp. israelensis or Lysinibacillus sphaericus in Culex mosquitoes.
AB  - Arsenic contamination of global water supplies has come to the forefront in
      policy decisions in recent decades. However, the effects of arsenic on lower
      trophic levels of insects inhabiting contaminated ecosystems are not well
      understood. One approach to document both acute and sublethal effects of
      toxicants like arsenic is to assay them in combination with microbial pathogens
      to evaluate shifts in survival curves of the test organisms. Larvae of Culex
      quinquefasciatus and Culex tarsalis were reared in water containing 0 or 1 000
      MUg/L of arsenate or arsenite. Fourth instars were then exposed to a range of
      doses of Bacillus thuringiensis subsp. israelensis (Bti) or Lysinibacillus
      sphaericus (Ls), with shifts in lethal concentrations determined. Arsenic
      accumulation in 4th instars was also quantified, and a relative growth index
      (RGI) calculated for the treatments and compared to controls. Larvae of both
      species accumulated between 4 447 +/- 169 ng As/g and 6 983 +/- 367 ng As/g,
      though RGI values indicated accumulation did not affect growth and development.
      In all cases, the LC50 's and LC90 's of Cx. quinquefasciatus exposed jointly
      with arsenic and Bti/Ls were higher than Cx. tarsalis. Cx. tarsalis reared in
      arsenite showed a significant reduction in their Bti LC90 values compared to the
      control, indicating a sublethal effect of Bti. When exposed jointly with Ls,
      arsenite was more toxic than arsenate in Cx. tarsalis. Overall, these results
      indicate tolerance of these Culex species to arsenic exposures, and why this may
      occur is discussed. 

PMID- 23956097
TI  - History of infertility and risk of gestational diabetes mellitus: a prospective
      analysis of 40,773 pregnancies.
AB  - Studies of delayed conception and risk of gestational diabetes (GDM) are sparse,
      although common underlying mechanisms are plausible, including insulin resistance
      and inflammation. The association between a history of infertility and GDM was
      assessed prospectively among 40,773 eligible pregnancies in the US Nurses' Health
      Study II cohort (1989-2001). Biennial questionnaires provided updated information
      on infertility and several lifestyle and health-related characteristics.
      Multivariable log-binomial models with generalized estimating equations were used
      to compute risk ratios and 95% confidence intervals, adjusting for age,
      prepregnancy body mass index (weight (kg)/height (m)(2)), and additional
      potential confounders. GDM occurred among 1,405 (5.2%) women. A prepregnancy
      history of infertility was reported by 5,497 (20.5%) participants and was
      significantly associated with a 39% greater risk of GDM (risk ratio (RR) = 1.39,
      95% confidence interval (CI): 1.24, 1.57; P < 0.001). Underlying reasons for
      infertility associated with GDM included ovulation disorders (RR = 1.52, 95% CI:
      1.23, 1.87; P < 0.001) and tubal blockage (RR = 1.83, 95% CI: 1.20, 2.77; P =
      0.005). The association of cervical mucus disorder with GDM was of borderline
      significance (RR = 1.70, 95% CI: 0.88, 3.30; P = 0.11). Endometriosis (RR = 1.27,
      95% CI: 0.70, 2.31; P = 0.43) and male factor infertility (RR = 1.12, 95% CI:
      0.78, 1.61; P = 0.55) were not associated with GDM risk. These novel findings
      suggest that infertility, particularly from ovulation disorders and tubal
      blockage, is associated with an increased GDM risk. Further research is needed to
      identify mechanisms or common underlying metabolic dysfunction explaining these
      observations. 

PMID- 23956098
TI  - RE: "Need for more individual-level meta-analyses in social epidemiology: example
      of job strain and coronary heart disease".

PMID- 23956099
TI  - RE: "Need for more individual-level meta-analyses in social epidemiology: example
      of job strain and coronary heart Disease".

PMID- 23956100
TI  - Treatment with anticancer agents induces dysregulation of specific Wnt signaling
      pathways in human ovarian luteinized granulosa cells in vitro.
AB  - Chemotherapy has been associated with premature ovarian failure and infertility
      in women with cancer. It is well known that anticancer drugs reduce the
      primordial follicle pool and harm the ovarian blood vascularization leading to
      ovarian atrophy. However, their mechanism of injury still remains unclear. The
      aim of this study was to identify the cellular mechanisms involved in the
      toxicity of chemotherapy drugs belonging to different classes on human ovarian
      luteinized granulosa cells (LGCs). Treatment with doxorubicin (DXR), paclitaxel
      (PC), and cisplatin (CP) affected LGCs viability by inducing apoptosis and
      downregulating both estrogen receptor beta and follicle-stimulating hormone
      receptor in a dose-dependent manner. Several members of the WNT signaling pathway
      are expressed in granulosa cells where they regulate follicle development,
      ovulation, and luteinization. Here we show that treatment with DXR, PC, and CP
      induced upregulation of WNT4 expression, whereas WNT3 expression was
      downregulated by DXR and PC and upregulated by CP. Analysis of the WNT3
      downstream signaling pathway showed that total beta-catenin protein levels were
      reduced upon treatment with DXR and PC. Additionally, restoration of beta-catenin
      signaling by lithium chloride protected LGCs from the injury induced by
      chemotherapy. The in vitro LGC toxicity model described might represent a tool to
      identify components of specific signaling pathways, such as the Wnt pathway, that
      can be targeted in order to limit the follicular damage caused by chemotherapy. 

PMID- 23956101
TI  - A multifactorial approach to hepatobiliary transporter assessment enables
      improved therapeutic compound development.
AB  - The bile salt export pump (BSEP) is expressed at the canalicular domain of
      hepatocytes, where it serves as the primary route of elimination for monovalent
      bile acids (BAs) into the bile canaliculi. The most compelling evidence linking
      dysfunction in BA transport with liver injury in humans is found with carriers of
      mutations that render BSEP nonfunctional. Based on mounting evidence, there
      appears to be a strong association between drug-induced BSEP interference and
      liver injury in humans; however, causality has not been established. For this
      reason, drug-induced BSEP interference is best considered a susceptibility factor
      for liver injury as other host- or drug-related properties may contribute to the
      development of hepatotoxicity. To better understand the association between BSEP
      interference and liver injury in humans, over 600 marketed or withdrawn drugs
      were evaluated in BSEP expressing membrane vesicles. The example of a compound
      that failed during phase 1 human trials is also described, AMG 009. AMG 009
      showed evidence of liver injury in humans that was not predicted by preclinical
      safety studies, and BSEP inhibition was implicated. For 109 of the drugs with
      some effect on in vitro BSEP function, clinical use, associations with
      hepatotoxicity, pharmacokinetic data, and other information were annotated. A
      steady state concentration (C(ss)) for each of these annotated drugs was
      estimated, and a ratio between this value and measured IC50 potency values were
      calculated in an attempt to relate exposure to in vitro potencies. When factoring
      for exposure, 95% of the annotated compounds with a C(ss)/BSEP IC50 ratio >= 0.1
      were associated with some form of liver injury. We then investigated the
      relationship between clinical evidence of liver injury and effects to multidrug
      resistance-associated proteins (MRPs) believed to play a role in BA homeostasis.
      The effect of 600+ drugs on MRP2, MRP3, and MRP4 function was also evaluated in
      membrane vesicle assays. Drugs with a C(ss)/BSEP IC50 ratio >= 0.1 and a
      C(ss)/MRP IC50 ratio >= 0.1 had almost a 100% correlation with some evidence of
      liver injury in humans. These data suggest that integration of exposure data, and
      knowledge of an effect to not only BSEP but also one or more of the MRPs, is a
      useful tool for informing the potential for liver injury due to altered BA
      transport.

PMID- 23956102
TI  - Regioselective hydroarylations and parallel kinetic resolution of Vince lactam.
AB  - Two regioselective and complementary hydroarylation reactions of an unsymmetrical
      cyclic olefin have been developed. The products can be transformed in one step
      into constrained gamma-amino acids. Regioselective arylation of Vince lactam is
      controlled by the choice of phosphine ligand enantiomer and the substituent on
      the amide nitrogen atom. The method was extended to a general regiodivergent
      parallel kinetic resolution of the racemic lactam. 

PMID- 23956103
TI  - Effect of leptin on the gluconeogenesis in calf hepatocytes cultured in vitro.
AB  - We have investigated the effect of leptin on gluconeogenesis in the liver.
      Hepatocytes were cultured and treated with 0, 2.5, 5, 10, 50, 100 ng/mL of leptin
      in groups I, II, III, IV, V, and VI, respectively. mRNA expression and enzyme
      activity of pyruvate carboxylase and phosphoenolpyruvate carboxykinase were
      determined by real-time fluorescence quantitative RT-PCR and biochemical kits,
      respectively. Compared with group I, mRNA expression of pyruvate carboxylase and
      phosphoenolpyruvate carboxykinase in groups III, IV, V, and VI were significantly
      lower (P < 0.01). Pyruvate carboxylase and phosphoenolpyruvate carboxykinase
      enzyme activity decreased significantly (P < 0.05) when leptin concentration
      exceeded 5 and 10 ng/mL, respectively. These results indicate that leptin
      markedly downregulated mRNA expression and enzyme activity of pyruvate
      carboxylase and phosphoenolpyruvate carboxykinase in hepatocytes, which suggests
      that high concentrations of LP inhibit hepatocyte gluconeogenesis, thus making
      negative energy balance more serious.

PMID- 23956105
TI  - Autologous fat transplantation for the temporalis muscle flap donor site: our
      experience with 45 cases.
AB  - BACKGROUND: Temporal depression after temporalis muscle flap transposition is
      characterized by a concavity of the soft tissue and associated with the relief of
      the orbital rim and zygomatic arch. The purpose of this study was to describe the
      use of autologous fat grafting for the treatment of postsurgical temporal contour
      deformities. METHODS: Between March 2008 and April 2011, 45 patients were treated
      with lipofilling. A virtual 3-dimensional preoperative assessment was used to
      objectively quantify the loss of volume of the affected side. Two different
      methods were used to evaluate the surgical outcomes. RESULTS: A noticeable soft
      tissue augmentation of the temporal region was noted in all cases. In 35
      patients, a second procedure was required and in 1 patient, a third procedure was
      required. The final result was assessed as fully satisfactory by 39 patients
      (86.6%), as satisfactory by 5 patients (11.1%), and as unsatisfactory by 1
      patient (2.2%). CONCLUSION: We believe that structural fat grafting at the
      temporalis muscle flap donor site is an effective technique that provides a high
      satisfaction rate and only a few complications.

PMID- 23956104
TI  - Parental broader autism subphenotypes in ASD affected families: relationship to
      gender, child's symptoms, SSRI treatment, and platelet serotonin.
AB  - Relationships between parental broader autism phenotype (BAP) scores, gender,
      selective serotonin reuptake inhibitor (SSRI) treatment, serotonin (5HT) levels,
      and the child's symptoms were investigated in a family study of autism spectrum
      disorder (ASD). The Broader Autism Phenotype Questionnaire (BAPQ) was used to
      measure the BAP of 275 parents. Fathers not taking SSRIs (F-SSRI; n = 115) scored
      significantly higher on BAP Total and Aloof subscales compared to mothers not
      receiving treatment (M-SSRI; n = 136.) However, mothers taking SSRIs (M + SSRI; n
      = 19) scored higher than those not taking medication on BAP Total and Rigid
      subscales, and they were more likely to be BAPQ Total, Aloof, and Rigid positive.
      Significant correlations were noted between proband autism symptoms and parental
      BAPQ scores such that Total, Aloof, and Rigid subscale scores of F-SSRI
      correlated with proband restricted repetitive behavior (RRB) measures on the
      ADOS, CRI, and RBS-R. However, only the Aloof subscale score of M + SSRI
      correlated with proband RRB on the ADOS. The correlation between the BAPQ scores
      of mothers taking SSRIs and child scores, as well as the increase in BAPQ scores
      of this group of mothers, requires careful interpretation and further study
      because correlations would not withstand multiple corrections. As expected by
      previous research, significant parent-child correlations were observed for 5HT
      levels. However, 5HT levels were not correlated with behavioral measures. Study
      results suggest that the expression of the BAP varies not only across parental
      gender, but also across individuals using psychotropic medication and those who
      do not.

PMID- 23956106
TI  - The phenotype range of achondrogenesis 1A.
AB  - Achondrogenesis 1A (ACG1A; OMIM 200600) is an autosomal recessive perinatally
      lethal skeletal dysplasia comprising intrauterine growth failure, micromelia,
      minor facial anomalies, deficient ossification of the skull, absent or extremely
      defective spinal ossification, short beaded ribs, and short deformed long bones
      with a stellate appearance. ACG1A is caused by mutations in the TRIP11 gene,
      resulting in deficiency of the Golgi microtubule associated protein 210. In this
      study we describe dizygotic twins with a clinical and radiological phenotype of
      ACG1A who were homozygous for a novel nonsense mutation in the TRIP11 gene. In
      addition, another patient with a milder manifestation, not readily
      distinguishable from those of other lethal skeletal dysplasias, was found to be a
      compound heterozygote for a nonsense mutation and a deletion of the 3' end of the
      TRIP11 gene. We conclude that mutations of the TRIP11 gene may encompass a wider
      phenotypic range than previously recognized.

PMID- 23956107
TI  - Reduction of adipogenesis and lipid accumulation by Taraxacum officinale
      (Dandelion) extracts in 3T3L1 adipocytes: an in vitro study.
AB  - In this in vitro study, we have investigated the ability of Taraxacum officinale
      (dandelion) to inhibit adipocyte differentiation and lipogenesis in 3T3-L1
      preadipocytes. HPLC analysis of the three plant extracts used in this study-leaf
      and root extracts and a commercial root powder-identified caffeic and chlorogenic
      acids as the main phenolic constituents. Oil Red O staining and triglyceride
      levels analysis showed decreased lipid and triglyceride accumulation,
      respectively. Cytotoxicity was assessed with the MTT assay showing non-toxic
      effect among the concentrations tested. DNA microarray analysis showed that the
      extracts regulated the expression of a number of genes and long non-coding RNAs
      that play a major role in the control of adipogenesis. Taken together, our
      results indicate that the dandelion extracts used in this study may play a
      significant role during adipogenesis and lipid metabolism, and thus, supporting
      their therapeutic interest as potential candidates for the treatment of obesity.

PMID- 23956108
TI  - Enrichment of steroid hormones in water with porous and hydrophobic polymer-based
      SPE followed by HPLC-UV determination.
AB  - There have been great concerns about the persistence of steroid hormones in
      surface water. Since the concentrations of these compounds in water samples are
      usually at a trace level, the efficient enrichment of steroid hormones is vital
      for further analysis. In this work, a porous and hydrophobic polymer was
      synthesized and characterized. The composition of solvent used as porogen in the
      synthetic process was shown to have an effect on the morphology of the polymer,
      which was successfully used as an SPE sorbent for simultaneously enriching
      steroid hormones in surface water samples. The recoveries of the steroid hormones
      on the custom-made polymer ranged from 93.4 to 106.2%, whereas those on
      commercialized ENVI-18, LC-18, and Oasis HLB ranged from 54.8 to 104.9, 66 to
      93.6, and 77.2 to 106%, respectively. Five types of steroid hormones were
      simultaneously measured using HPLC-UV after they were enriched by the custom-made
      sorbent. Based on these findings, the SPE-HPLC method was developed. The LODs of
      this method for estriol, estradiol, estrone, androstenedione, progesterone were
      0.07, 0.43, 0.61, 0.27, and 0.42 MUg/L, respectively, while precision and
      reproducibility RSDs were <6.40 and 7.49%, respectively. 

PMID- 23956110
TI  - Comparison of fatty acid contents and composition in major lipid classes of
      larvae and adults of mosquitoes (Diptera: Culicidae) from a steppe region.
AB  - Emerging aquatic insects, including mosquitoes, are known to transfer to
      terrestrial ecosystems specific essential biochemicals, such as polyunsaturated
      fatty acids (PUFA). We studied fatty acid (FA) composition and contents of
      dominant mosquito populations (Diptera: Culicidae), that is, Anopheles messeae,
      Ochlerotatus caspius, Oc. flavescens, Oc. euedes, Oc. subdiversus, Oc.
      cataphylla, and Aedes cinereus, inhabited a steppe wetland of a temperate climate
      zone to fill up the gap in their lipid knowledge. The polar lipid and
      triacylglycerol fractions of larvae and adults were compared. In most studied
      mosquito species, we first found and identified a number of short-chain PUFA, for
      example, prominent 14:2n-6 and 14:3n-3, which were not earlier documented in
      living organisms. These PUFA, although occurred in low levels in adult
      mosquitoes, can be potentially used as markers of mosquito biomass in terrestrial
      food webs. We hypothesize that these acids might be synthesized (or
      retroconverted) by the mosquitoes. Using FA trophic markers accumulated in
      triacylglycerols, trophic relations of the mosquitoes were accessed. The larval
      diet comprised green algae, cryptophytes, and dinoflagellates and provided the
      mosquitoes with essential n-3 PUFA, linolenic, and eicosapentaenoic acids. As a
      result, both larvae and adults of the studied mosquitoes had comparatively high
      content of the essential PUFA. Comparison of FA proportions in polar lipids
      versus storage lipids shown that during mosquito metamorphosis transfer of
      essential eicosapentaenoic and arachidonic acids from the reserve in storage
      lipids of larvae to functional polar lipids in adults occurred. 

PMID- 23956111
TI  - Palladium-catalyzed hydrobenzylation of ortho-tolyl alkynyl ethers by benzylic C
      H activation: remarkable alkynoxy-directing effect.
AB  - It's selective: The title reaction involves palladium(0)-catalyzed insertion of
      C=C bonds into benzylic C(sp(3))-H bonds, thus providing efficient access to 2
      methylene-2,3-dihydrobenzofurans, which transform into benzofurans upon treatment
      with a weak acid (e.g., AcOH) and electrophiles. The alkynoxy group serves as a
      directing group in promoting C-H bond functionalization.

PMID- 23956109
TI  - A chimeric SERM-histone deacetylase inhibitor approach to breast cancer therapy.
AB  - Breast cancer remains a significant cause of death in women, and few therapeutic
      options exist for estrogen receptor negative (ER (-)) cancers. Epigenetic
      reactivation of target genes using histone deacetylase (HDAC) inhibitors has been
      proposed in ER (-) cancers to resensitize to therapy using selective estrogen
      receptor modulators (SERMs) that are effective in ER (+) cancer treatment. Based
      upon preliminary studies in ER (+) and ER (-) breast cancer cells treated with
      combinations of HDAC inhibitors and SERMs, hybrid drugs, termed SERMostats, were
      designed with computational guidance. Assay for inhibition of four type I HDAC
      isoforms and antagonism of estrogenic activity in two cell lines yielded a
      SERMostat with 1-3 MUM potency across all targets. The superior hybrid caused
      significant cell death in ER (-) human breast cancer cells and elicited cell
      death at the same concentration as the parent SERM in combination treatment and
      at an earlier time point. 

PMID- 23956112
TI  - Different paths to sexual size dimorphism in two praying mantids, Pseudomantis
      albofimbriata and Hierodula majuscula.
AB  - Sexual size dimorphism (SSD) is widespread among diverse animal taxa and has
      attracted the attention of evolutionary biologists for over a century. SSD is
      likely to be adaptive and the result of divergent selection on different size
      optima for males and females, given their different roles in reproduction. The
      developmental trajectory leading to SSD may help us to understand how selection
      acts on male and female size. Here, we describe the growth and development of two
      Australian praying mantids, Pseudomantis albofimbriata and Hierodula majuscula
      including the number of moults, time to adulthood, size at each moult, and the
      degree of SSD. While both species exhibit the common pattern of female-biased
      SSD, the number of moults required for individuals to reach adulthood differed
      between males and females and between species. Despite their larger adult size,
      P. albofimbriata females require fewer moults and less time than males to reach
      adulthood, but are significantly larger than males from the second instar
      onwards. In contrast, H. majuscula males reached adulthood in fewer moults, and
      less time than females, however males and females did not differ in size until
      females went through their final moult into adulthood. H. majuscula also required
      more time and more moults to reach adulthood than P. albofimbriata. We discuss
      these different developmental pathways in light of the existing knowledge of
      reproductive biology for each species. We also suggest that these differences may
      relate to the different phenologies that occur in strongly seasonal temperate
      environments compared with those in the tropics. This study provides evidence
      that SSD can result from two different patterns of growth and development in
      closely related species.

PMID- 23956113
TI  - Outpatient management of vascular access devices in children receiving
      radiotherapy: complications and morbidity.
AB  - BACKGROUND: When treating children with cancer, long-term venous access is
      critical. This is especially true in the context of children receiving daily
      radiation therapy (RT) under general anesthesia. We have previously reported
      <0.1% risk of complications in complications in over 4,040 pediatric treatments
      under general anesthesia in our outpatient facility. Here, we present our
      experience with venous catheter access techniques in children receiving daily
      proton RT. PROCEDURE: After Institutional Review Board approval, we reviewed our
      center's records between September 9, 2004 and October 23, 2012 with respect to
      complications and morbidity of indwelling catheters in our pediatric patients.
      RESULTS: Vascular access device (VAD) types included: 110 patients with
      indwelling port-a-cath (PAC), 34 PICC line devices, and 34 central venous
      catheter (CVC) devices in 170 patients. Median catheter life during RT was 43
      days (range 1-86 days) with a total of 7,169 total catheter days while patients
      received RT. A 14% PAC complication rate included negative blood return (6.3%)
      and infection (3.6%). Complication rates for PICC and CVC access devices were 38%
      and 20.5%, respectively (chi(2) P = 0.007 when compared with PAC). Most frequent
      complications for PICC lines were no blood return (11.7%), and infection or
      occlusion (8.8% each). CVC complications were breakage (8.8%) and infection
      (8.8%). Access device replacement rates were 3.6% (PAC), 14.7% (PICC), and 8.8%
      (CVC). CONCLUSIONS: In the outpatient delivery of RT to children, indwelling
      ports provide greater convenience, less likelihood of infection or complication,
      and greater durability than PICC or CVC devices.

PMID- 23956114
TI  - Local control for identifying subgroups of interest in observational research:
      persistence of treatment for major depressive disorder.
AB  - Caregivers are regularly faced with decisions between competing treatments. Large
      observational health care databases provide a golden opportunity for research on
      heterogeneity in patient response to guide caregiver decisions, due to their
      sample size, diverse populations, and real-world setting. Local control is a
      promising tool for using observational data to detect patient subgroups with
      differential response on one treatment relative to another. While standard data
      mining approaches find subgroups with optimal responses for a particular
      population, detecting subgroups that reveal treatment differences while also
      adjusting for confounding in observational data is challenging. Local control
      utilizes unsupervised clustering to form non-parametric patient-level
      counterfactual treatment differences and displays them as an observed
      distribution of effect-size estimates. Classification and regression trees (CART)
      then find the factors that drive the greatest outcome differentiation between
      treatments. In this manuscript, we demonstrate the use of this two-step strategy
      using local control plus CART to identify depression patients most (least) likely
      to benefit from treatment with duloxetine relative to extended-release
      venlafaxine. Prior medication costs and age were found to be factors most
      associated with differential outcome, with prior medication costs remaining as an
      important factor after sensitivity analyses using a second dataset.

PMID- 23956115
TI  - Evaluation of spatial and temporal patterns of insect damage and aflatoxin level
      in the pre-harvest corn fields to improve management tactics.
AB  - Spatial and temporal patterns of insect damage in relation to aflatoxin
      contamination in a corn field with plants of uniform genetic background are not
      well understood. After previous examination of spatial patterns of insect damage
      and aflatoxin in pre-harvest corn fields, we further examined both spatial and
      temporal patterns of cob- and kernel-feeding insect damage, and aflatoxin level
      with two samplings at pre-harvest in 2008 and 2009. The feeding damage by each of
      the ear/kernel-feeding insects (i.e., corn earworm/fall armyworm damage on the
      silk/cob, and discoloration of corn kernels by stink bugs) and maize weevil
      population were assessed at each grid point with five ears. Sampling data showed
      a field edge effect in both insect damage and aflatoxin contamination in both
      years. Maize weevils tended toward an aggregated distribution more frequently
      than either corn earworm or stink bug damage in both years. The frequency of
      detecting aggregated distribution for aflatoxin level was less than any of the
      insect damage assessments. Stink bug damage and maize weevil number were more
      closely associated with aflatoxin level than was corn earworm damage. In
      addition, the indices of spatial-temporal association (chi) demonstrated that the
      number of maize weevils was associated between the first (4 weeks pre-harvest)
      and second (1 week pre-harvest) samplings in both years on all fields. In
      contrast, corn earworm damage between the first and second samplings from the
      field on the Belflower Farm, and aflatoxin level and corn earworm damage from the
      field on the Lang Farm were dissociated in 2009. 

PMID- 23956116
TI  - A novel recombinant Salmonella vaccine enhances the innate immunity of NK cells
      against acute myeloid leukaemia cells Kasumi-1 in vitro.
AB  - Minor histocompatibility antigen HA-1-specific cytotoxic lymphocyte (CTL) clones
      have apparent anti-leukaemic efficacy, and the AML/ETO gene is a special fusion
      gene in leukaemic cells. Thus, we hypothesised that a vaccine targeting HA-1 and
      AML/ETO could stimulate NK cells to target leukaemia cells. Furthermore, we
      packaged the vaccine using attenuated Salmonella to enhance its immuno-activity.
      Expression of the NK cell-activating ligand ULBP2 was notably elevated upon
      packaging in a co-recombinant group. An AML/ETO single plasmid gave the weakest
      vaccine. The level of miR-182, which targets ULBP2, significantly decreased with
      increasing IFN-gamma and granzyme B in a co-recombinant group. In summary, DNA
      vaccines including AML/ETO and HA-1 fragments significantly enhance the innate
      immunity of NK cells in vitro. 

PMID- 23956117
TI  - Redefining the progeroid form of Ehlers-Danlos syndrome: report of the fourth
      patient with B4GALT7 deficiency and review of the literature.
AB  - Proteoglycans are a component of the extracellular matrix and are critical for
      cellular and tissue function. Mutations in proteoglycan components and enzymes
      involved in proteoglycan synthesis have been implicated in several growth
      disorders, with common features including short stature and skeletal dysplasia.
      For example, mutations in B4GALT7, a gene whose protein product catalyzes
      proteoglycan synthesis, have been associated with the rare progeroid variant of
      Ehlers-Danlos syndrome. Here, we conducted exome sequencing in a patient with a
      previously undiagnosed growth disorder and identified compound heterozygous
      mutations in B4GALT7. This patient is just the fourth individual with genetically
      confirmed progeroid variant of Ehlers-Danlos syndrome. The mutations include a
      previously characterized c.808C>T p.Arg270Cys substitution, and a novel c.122T>C
      p.Leu41Pro substitution. We demonstrate that the novel mutation caused decreased
      levels of the enzyme, supporting the pathogenicity of the mutation. Our report
      identifies a novel mutation in B4GALT7 causing the progeroid variant of Ehlers
      Danlos syndrome and contributes an extensive phenotypic characterization of a
      patient with the syndrome. We also reviewed the previous literature in addition
      to the present patient, and conclude that the key features associated with
      B4GALT7 deficiency are short stature, developmental anomalies of the forearm
      bones and elbow, and bowing of the extremities, in addition to the classic
      features of Ehlers-Danlos syndrome. This report helps define the phenotype of the
      progeroid variant of Ehlers-Danlos syndrome and furthers our understanding of the
      effect of proteoglycan defects in growth disorders.

PMID- 23956118
TI  - Improving our ability to classify rhinologic disorders.

PMID- 23956119
TI  - Specific glial functions contribute to schizophrenia susceptibility.
AB  - Schizophrenia is a highly polygenic brain disorder. The main hypothesis for
      disease etiology in schizophrenia primarily focuses on the role of dysfunctional
      synaptic transmission. Previous studies have therefore directed their
      investigations toward the role of neuronal dysfunction. However, recent studies
      have shown that apart from neurons, glial cells also play a major role in
      synaptic transmission. Therefore, we investigated the potential causal
      involvement of the 3 principle glial cell lineages in risk to schizophrenia. We
      performed a functional gene set analysis to test for the combined effects of
      genetic variants in glial type-specific genes for association with schizophrenia.
      We used genome-wide association data from the largest schizophrenia sample to
      date, including 13 689 cases and 18 226 healthy controls. Our results show that
      astrocyte and oligodendrocyte gene sets, but not microglia gene sets, are
      associated with an increased risk for schizophrenia. The astrocyte and
      oligodendrocyte findings are related to astrocyte signaling at the synapse,
      myelin membrane integrity, glial development, and epigenetic control. Together,
      these results show that genetic alterations underlying specific glial cell type
      functions increase susceptibility to schizophrenia and provide evidence that the
      neuronal hypothesis of schizophrenia should be extended to include the role of
      glia. 

PMID- 23956121
TI  - Uniformly dispersed and controllable ligand-free silver-nanoparticle-decorated
      TiO2 nanotube arrays with enhanced photoelectrochemical behaviors.
AB  - Homogeneously dispersed silver nanoparticles (AgNPs) were successfully decorated
      onto the surface of TiO2 nanotube arrays (TNTA) by means of an in situ
      photoreduction method. TNTA films as supports exhibit excellent properties to
      prevent agglomeration of AgNPs, and they also avoid using polymer ligands, which
      is deleterious to enhancing the properties of the fabricated NPs. The silver
      particle size and its content could be controlled just by changing the immersion
      time. Detailed SEM and TEM analyses combined with energy-dispersive X-ray
      spectroscopy analyses with different immersion times (5, 10, 30, 60 min) have
      revealed the variation tendency. The prepared Ag/TNTA composite films were also
      characterized by XRD, X-ray photoelectron spectroscopy, and high-resolution TEM.
      The UV/Vis diffuse reflectance spectra displayed a redshift of the absorption
      peak with the growth of AgNPs. The photocurrent response and the
      photoelectrocatalytic degradation of methyl orange (MO) were used to evaluate the
      photoelectrochemical properties of the fabricated samples. The results showed
      that the photocurrent response and photoelectrocatalytic activity largely
      depended on the loaded Ag particle size and content. TNTA films with a diameter
      of 17.92 nm and silver content of 1.15 at% showed the highest photocurrent
      response and degradation rate of MO. The enhanced properties could be attributed
      to the synergistic effect between AgNPs and TiO2. To make good use of this
      effect, particle size and silver content should be well controlled to develop the
      electron charge and discharge process during the photoelectrical process. Neither
      smaller nor larger AgNPs caused decreased photoelectrical properties.

PMID- 23956120
TI  - Superior temporal sulcus disconnectivity during processing of metaphoric gestures
      in schizophrenia.
AB  - The left superior temporal sulcus (STS) plays an important role in integrating
      audiovisual information and is functionally connected to disparate regions of the
      brain. For the integration of gesture information in an abstract sentence context
      (metaphoric gestures), intact connectivity between the left STS and the inferior
      frontal gyrus (IFG) should be important. Patients with schizophrenia have
      problems with the processing of metaphors (concretism) and show aberrant
      structural connectivity of long fiber bundles. Thus, we tested the hypothesis
      that patients with schizophrenia differ in the functional connectivity of the
      left STS to the IFG for the processing of metaphoric gestures. During functional
      magnetic resonance imaging data acquisition, 16 patients with schizophrenia (P)
      and a healthy control group (C) were shown videos of an actor performing gestures
      in a concrete (iconic, IC) and abstract (metaphoric, MP) sentence context. A
      psychophysiological interaction analysis based on the seed region from a previous
      analysis in the left STS was performed. In both groups we found common positive
      connectivity for IC and MP of the STS seed region to the left middle temporal
      gyrus (MTG) and left ventral IFG. The interaction of group (C>P) and gesture
      condition (MP>IC) revealed effects in the connectivity to the bilateral IFG and
      the left MTG with patients exhibiting lower connectivity for the MP condition. In
      schizophrenia the left STS is misconnected to the IFG, particularly during the
      processing of MP gestures. Dysfunctional integration of gestures in an abstract
      sentence context might be the basis of certain interpersonal communication
      problems in the patients. 

PMID- 23956122
TI  - RNA-guided genome editing in plants using a CRISPR-Cas system.
AB  - Precise and straightforward methods to edit the plant genome are much needed for
      functional genomics and crop improvement. Recently, RNA-guided genome editing
      using bacterial Type II cluster regularly interspaced short palindromic repeats
      (CRISPR)-associated nuclease (Cas) is emerging as an efficient tool for genome
      editing in microbial and animal systems. Here, we report the genome editing and
      targeted gene mutation in plants via the CRISPR-Cas9 system. Three guide RNAs
      (gRNAs) with a 20-22-nt seed region were designed to pair with distinct rice
      genomic sites which are followed by the protospacer-adjacent motif (PAM). The
      engineered gRNAs were shown to direct the Cas9 nuclease for precise cleavage at
      the desired sites and introduce mutation (insertion or deletion) by error-prone
      non-homologous end joining DNA repairing. By analyzing the RNA-guided genome
      editing events, the mutation efficiency at these target sites was estimated to be
      3-8%. In addition, the off-target effect of an engineered gRNA-Cas9 was found on
      an imperfectly paired genomic site, but it had lower genome-editing efficiency
      than the perfectly matched site. Further analysis suggests that mismatch position
      between gRNA seed and target DNA is an important determinant of the gRNA-Cas9
      targeting specificity, and specific gRNAs could be designed to target more than
      90% of rice genes. Our results demonstrate that the CRISPR-Cas system can be
      exploited as a powerful tool for gene targeting and precise genome editing in
      plants. 

PMID- 23956123
TI  - A passive repression mechanism that hinders synergic transcriptional activation
      by heat shock factors involved in sunflower seed longevity.

PMID- 23956124
TI  - Learning in networks: individual teacher learning versus organizational learning
      in a regional health-promoting schools network.
AB  - To change a school into a health-promoting organization, organizational learning
      is required. The evaluation of an Austrian regional health-promoting schools
      network provides qualitative data on the views of the different stakeholders on
      learning in this network (steering group, network coordinator and representatives
      of the network schools; n = 26). Through thematic analysis and deep-structure
      analyses, the following three forms of learning in the network were identified:
      (A) individual learning through input offered by the network coordination, (B)
      individual learning between the network schools, i.e. through exchange between
      the representatives of different schools and (C) learning within the
      participating schools, i.e. organizational learning. Learning between (B) or
      within the participating schools (C) seems to be rare in the network; concepts of
      individual teacher learning are prevalent. Difficulties detected relating to the
      transfer of information from the network to the member schools included barriers
      to organizational learning such as the lack of collaboration, coordination and
      communication in the network schools, which might be effects of the school system
      in which the observed network is located. To ensure connectivity of the
      information offered by the network, more emphasis should be put on linking health
      promotion to school development and the core processes of schools. 

PMID- 23956125
TI  - Potential cotton aphid, Aphis gossypii, population suppression by arthropod
      predators in upland cotton.
AB  - The cotton aphid, Aphis gossypii Glover, predation rate of convergent lady
      beetle, Hippodamia convergens Guerin-Meneville, was determined by assigning a
      single predator randomly to each of four prey density treatments in the
      laboratory. Prey densities included 25, 50, 100, and 200 aphids per Petri dish
      arena. Predation response was recorded at 1, 4, 8, 16, 24, and 48 h after
      assigning predators to their prey treatments. Rate of consumption increased
      through time, with all 25 aphids consumed during the first 4 h of the experiment.
      At the highest density, adult lady beetle consumed on average 49, 99, 131, 163,
      183, and 200 aphids within 1, 4, 8, 16, 24 and 48 h, respectively. Predators
      showed a curvilinear feeding response in relation to total available time,
      indicating that convergent lady beetles have the potential to suppress larger
      populations of aphids through continuous feeding by regulating their predation
      efficiency during feeding. The analysis of age-specific mortality in absence of
      prey revealed that lady beetles could survive for an extended period of time
      (more than 2 weeks) without prey. The ability of a predator to survive without
      prey delays or prevents the rebound of pest populations that is a significant
      factor in natural biological control. A two-year field sampling of 10 cotton
      arthropod predator species showed that spiders (27%) were the most dominant
      foliage dwelling predators in the Texas High Plains cotton followed by convergent
      lady beetles (23.5%), hooded beetles (13.5%), minute pirate bugs (11%), green
      lacewings (9.5%), bigeyed bugs (7.5%), scymnus beetles (3%), soft-winged flower
      beetles (2%), damsel bugs (1.5%), and assassin bugs (1.5%). A field cage study
      showed that one H. convergens adult per plant released at prey density of one
      aphid per leaf kept the aphid population below economic threshold for the entire
      growing season. 

PMID- 23956126
TI  - Rhodium-catalyzed dynamic kinetic asymmetric transformations of racemic allenes
      by the [3+2] annulation of aryl ketimines.
AB  - Racemization required: Rhodium(I)-catalyzed C-H activation directed by
      unprotected ketimines initiates selective [3+2] cycloaddition with allenes,
      providing access to highly substituted indenylamines. The reaction proceeds
      through the dynamic kinetic asymmetric transformation of racemic allenes. The
      catalyst controls the enantio- and diastereoselectivity, the regioselectivities
      of the C-H activation and allene incorporation, as well as the E/Z ratio.

PMID- 23956127
TI  - Effect of plant nutrition on aphid size, prey consumption, and life history
      characteristics of green lacewing.
AB  - Plant quality can directly and indirectly affect the third trophic level. The
      predation by all the instars of green lacewing, Chrysoperla carnea (S.)
      (Neuroptera: Chrysopidae) on the cereal aphids, Rhopalosiphum padi (L.), and
      Sitobion avenae (F.) at varying nitrogen fertilizer levels was calculated under
      laboratory conditions. Wheat plants were grown on four nitrogen fertilizer levels
      and aphids were fed on these plants and subsequently offered as food to the C.
      carnea. Aphid densities of 10, 30, and 90 were offered to first, second, and
      third instar larvae of green lacewing. Increased nitrogen application improved
      nitrogen contents of the plants and also the body weight of cereal aphids feeding
      on them. Aphid consumption by green lacewings was reduced with the increase in
      nitrogen content in the host plants of aphids. Predation of both aphid species by
      first, second, and third instars larvae of C. carnea was highest on aphids reared
      on plants with the lowest rate of fertilization, suggesting a compensatory
      consumption to overcome reduced biomass (lower aphid size). Total biomass
      devoured by C. carnea on all nitrogen fertilizer treatments was not statistically
      different. Additionally, the heavier host prey influenced by the plant nutrition
      had an effect on the life history characteristics of green lacewings. The larval
      duration, pupal weight, pupal duration, fecundity, and male and female longevity
      were significantly affected by the level of nitrogen fertilization to the aphid's
      host plants, except for pupal duration when fed on S. avenae. This study showed
      that quantity of prey supplied to the larvae affects the prey consumption and
      thereafter the life history characteristics of green lacewings. 

PMID- 23956128
TI  - CBF gene expression in peach leaf and bark tissues is gated by a circadian clock.
AB  - CBF (C-repeat Binding Factor) transcription factors are part of the AP2/ERF
      (Apetala2-ethylene responsive factor) domain family of DNA-binding proteins that
      recognize a C-repeat response cis-acting element that regulates a number of cold
      responsive genes (CBF regulon). Induction of CBF gene expression by low
      temperature in Arabidopsis has been shown to be gated by a circadian clock. In
      peach (Prunus persica L.), five CBF genes are arranged in tandem on scaffold
      (linkage group) 5 of the peach genome. Since CBF gene regulation has been shown
      to be more complex in woody plants than herbaceous plants, the present study was
      conducted to determine if temperature-modulated CBF gene expression in peach leaf
      and bark tissues was also influenced by a circadian clock. One-year-old 'Loring'
      peach trees grafted on 'Bailey' rootstocks were entrained to a 12-h day/12-h
      night photoperiod at 25  degrees C. After 2 weeks, trees were exposed to 4 
      degrees C under continuous light for up to 48 h beginning at either subjective
      dawn + 4 h (ZT4; where ZT is Zeitgeber time) or subjective dawn + 16 h (ZT16)
      with leaf and bark tissues harvested at various time points. Gene expression of
      the five peach CBF genes and a DREB2 gene was assessed by real-time quantitative
      polymerase chain reaction. Results revealed a distinct gating of CBF gene
      expression by a circadian clock for four CBF genes in both leaf and bark tissues.
      CBF genes were highly induced by 4  degrees C in ZT4 leaf samples with expression
      peaking at 6-24 h depending on the specific CBF gene. In contrast, CBF gene
      expression was highly attenuated in leaf, and to a lesser extent in bark, samples
      exposed to 4  degrees C at ZT16. These results are similar to reports for
      Arabidopsis. Further experiments were conducted to verify environmental influence
      on the induction of CBF and DREB2 genes. In contrast to DREB2 genes from other
      dicots, the peach DREB2 ortholog was induced by both low temperature and
      dehydration. Induction of the peach CBFs and DREB2 by either low temperature or
      dehydration corresponded with regulatory motifs present in their promoter
      sequences. Low temperature and dehydration induction data for three peach
      dehydrin genes indicated that the regulation of these genes in peach is complex,
      with individual dehydrin gene expression being correlated with the expression of
      one or more CBF genes.

PMID- 23956129
TI  - Isolation and characterization of a TERMINAL FLOWER 1 homolog from Prunus
      serotina Ehrh.
AB  - Flowering control is one of the several strategies for gene containment of
      transgenic plants. TERMINAL FLOWER 1 (TFL1) is known to be involved in the
      transcriptional repression of genes for inflorescence development. Two TFL1
      transcripts with different 3' UTR were cloned from black cherry (Prunus serotina
      Ehrh.) using reverse transcription-polymerase chain reaction (RT-PCR) and rapid
      amplification of cDNA ends (RACE). Corresponding to the two TFL1 transcripts, two
      PsTFL1 gene sequences, 1248 bp and 1579 bp, were obtained and both contained the
      same 519 bp coding region which encoded a putative protein of 172 amino acid
      residues. The phylogenetic analysis of the amino acid sequences showed high
      identity of PsTFL1 to TFL1 orthologs of other Prunus species, including Yoshino
      cherry (Prunus * yedoensis Matsum.), peach (Prunus persica (L.) Batsch), apricot
      (Prunus armeniaca L.) and Japanese apricot (Prunus mume Sieb. et Zucc.). The real
      time quantitative PCR detected a single copy of PsTFL1 gene sequences in the
      black cherry genome with two alleles. The gene expression of PsTFL1 was examined
      in several tissues including the stems, leaves, shoot tips, and vegetative and
      floral buds. The highest mRNA level was detected in shoot tips, and the lowest
      level in the leaves. Transgenic Arabidopsis thaliana (L.) Heynh. plants
      overexpressing PsTFL1 showed significantly delayed flowering. These plants also
      showed largely increased vegetative growth, plant height, number of nodes,
      trichome density, and the conversion of flower to shoot was observed at each node
      and shoot apex.

PMID- 23956130
TI  - Investigating the relationship between COMT polymorphisms and working memory
      performance among childhood brain tumor survivors.
AB  - BACKGROUND: Survivors of childhood brain tumors are at increased risk for
      neurocognitive impairments, including deficits in abilities supported by frontal
      brain regions. Catechol-O-methyltransferase (COMT) metabolizes dopamine in the
      prefrontal cortex, with the Met allele resulting in greater dopamine availability
      and better performance on frontally mediated tasks compared to the Val allele.
      Given the importance of identifying resiliency factors against the emergence of
      cognitive late effects, the current study examined the relationship between COMT
      genotype and working memory performance among childhood brain tumor survivors.
      PROCEDURE: Children treated for a brain tumor with conformal radiation therapy (N
      = 50; mean age at irradiation = 7.41 +/- 3.41; mean age at assessment = 13.18 +/-
      2.88) were administered two computerized measures of working memory (self-ordered
      search verbal and object tasks). Buccal (cheek) swabs were used to provide tissue
      from which DNA was extracted. RESULTS: Findings revealed an association between
      COMT genotype and performance on the self-ordered verbal (P = 0.03) but not
      object task (P = 0.33). Better performance was found for the Met/Val group
      compared to either Met/Met or Val/Val. CONCLUSIONS: COMT may indicate a potential
      resiliency factor against neurocognitive effects of cancer and its treatment;
      however, there is a need for replication with larger samples of childhood brain
      tumor survivors.

PMID- 23956131
TI  - Interaction between optineurin and the bZIP transcription factor NRL.
AB  - Although the gene encoding optineurin (OPTN) is a causative gene for glaucoma and
      amyotrophic lateral sclerosis, it is ubiquitously expressed in all body tissues,
      including the retina. To study the function of OPTN in retinal ganglion cells as
      well as the whole retina, we previously isolated OPTN-interacting proteins and
      identified the gene encoding the bZIP transcription factor neural retina leucine
      zipper (NRL), which is a causative gene for retinitis pigmentosa. Herein, we
      investigated the binding between OPTN and NRL proteins in HeLaS3 cells. Co
      expression of HA-tagged NRL and FLAG-tagged OPTN in HeLaS3 cells followed by
      immunoprecipitation and Western blotting with anti-tag antibodies demonstrated
      the binding of these proteins in HeLaS3 cells, which was confirmed by proximity
      ligation assay. NRL is the first OPTN-binding protein to show eye-specific
      expression. A series of partial-deletion OPTN plasmids demonstrated that the tail
      region (423-577 amino acids [aa]) of OPTN was necessary for binding with NRL.
      Immunostaining showed that Optn (rat homologue of OPTN) was expressed in rat
      photoreceptors and localised in the cytoplasm of photoreceptor cells. This is a
      novel demonstration of Optn expression in photoreceptor cells. OPTN was not
      detected in photoreceptor nuclei under our experimental conditions. Further
      analyses are necessary to elucidate the function of OPTN and the significance of
      its possible binding with NRL in photoreceptor cells. 

PMID- 23956132
TI  - Instability and degenerative arthritis of the sternoclavicular joint: a current
      concepts review.
AB  - BACKGROUND: Injuries to the sternoclavicular (SC) joint typically occur with high
      energy mechanisms such as those obtained in automobile accidents or contact
      sports. Many disorders of the SC joint can be treated nonoperatively. However,
      surgical treatment may be indicated for locked posterior dislocations;
      symptomatic, chronic instability; or persistent, painful osteoarthritis that
      fails nonoperative therapy. PURPOSE: To provide an updated review on the current
      diagnosis and management of instability and degenerative arthritis of the SC
      joint. STUDY DESIGN: Current concepts review. METHODS: A preliminary PubMed
      database search using the terms sternoclavicular instability, dislocation,
      arthritis, resection, and stabilization was performed in August 2012. All
      anatomic and biomechanical studies, review articles, case reports, case series,
      and technique papers that were relevant to the topic were included. RESULTS: The
      search identified 929 articles, 321 of which, after screening of the titles and
      abstracts, were considered potentially relevant to this study. Of the 321
      articles, 30 were anatomic or imaging studies, 2 were biomechanical studies, 69
      were review papers, 189 were case series or reports, and 31 were technique
      papers. The majority of these studies were classified as evidence level 4, with a
      few scattered level 3 studies. Because the level of evidence obtained from this
      search was not adequate for systematic review (or meta-analysis), a current
      concepts review of the diagnosis and management of SC joint instability and
      degenerative arthritis is presented. CONCLUSION: Injuries to the SC joint are
      uncommon. Recognition and classification of these injuries are critical to proper
      management, thus minimizing potential long-term sequelae such as posttraumatic
      arthritis and recurrent instability. Although nonoperative therapy is the
      modality of choice in anterior dislocations, posterior dislocations require
      special attention because of the presence of vulnerable posterior hilar
      structures. Surgical management of chronic instability and degenerative arthritis
      of the SC joint includes resection arthroplasty of the medial clavicle with or
      without reconstruction of the sternoclavicular ligaments with graft material.
      Although resection is typically performed open, an arthroscopic technique is
      described that theoretically decreases operating and recovery times while also
      decreasing the risk of iatrogenic injury. Currently, when reconstruction is
      needed for stability, a figure-of-8 graft reconstruction is the recommended
      method based on biomechanical data and small clinical series.

PMID- 23956133
TI  - Arthroscopic capsular plication and labral preservation in borderline hip
      dysplasia: two-year clinical outcomes of a surgical approach to a challenging
      problem.
AB  - BACKGROUND: The role of hip arthroscopy in the treatment of patients with
      dysplasia is unclear because of the spectrum of dysplasia that exists. Patients
      with borderline dysplasia are generally not candidates for periacetabular
      osteotomy because of the invasive nature of the procedure. However, arthroscopy
      in dysplasia has had mixed results and has the potential to exacerbate
      instability. HYPOTHESIS: Patients with borderline dysplasia will demonstrate
      postoperative improvement, high satisfaction rates, and low reoperation rates
      after a surgical approach that includes arthroscopic labral repair augmented by
      capsular plication with inferior shift. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: Between April 2008 and November 2010, patients less than 40
      years old who underwent hip arthroscopy for symptomatic intra-articular hip
      disorders, with a lateral center-edge (CE) angle >=18 degrees  and <=25 degrees ,
      were included in this study. Patients with Tonnis grade 2 or greater, severe hip
      dysplasia (CE <=17 degrees ), and Legg-Calve-Perthes disease were excluded.
      Patient-reported outcome scores, including the modified Harris Hip Score (mHHS),
      Non-Arthritic Hip Score (NAHS), Hip Outcome Score-Sport-Specific Subscale (HOS
      SSS), Hip Outcome Score-Activity of Daily Living (HOS-ADL), and visual analog
      scale (VAS) for pain were obtained in all patients preoperatively and at 1, 2,
      and 3 years postoperatively. Revision surgery and complications were recorded for
      each group. RESULTS: A total of 26 patients met the criteria to be included in
      the study. Of these, 22 (85%) patients were available for follow-up. The mean (+/
      standard deviation) length of follow-up for this cohort was 27.5 +/- 5.5 months
      (range, 17-39 months) and the average age was 20 years (range, 14-39 years). The
      mean lateral CE angle was 22.2 degrees  (range, 18 degrees -25 degrees ) and the
      mean Tonnis angle was 5.8 degrees  (range, 0 degrees -17 degrees ). There was
      significant improvement in all patient-reported outcome scores (mHHS, NAHS, HOS
      SSS, and HOS-ADL) (P < .0001). There was a significant improvement in VAS scores
      from 5.8 to 2.9 (P < .0001). Overall patient satisfaction was 8.4 out of 10.
      Seventeen patients had good/excellent results (77%). Two patients required
      revision arthroscopy. CONCLUSION: Patients with borderline dysplasia have often
      fallen into a gray area between arthroscopy and periacetabular osteotomy, and
      viable treatment options have remained scarce. The current study demonstrates
      favorable results at 2-year follow-up for an arthroscopic approach that includes
      labral repair augmented by capsular plication with inferior shift.

PMID- 23956134
TI  - Performance-based outcomes after nonoperative treatment, discectomy, and/or
      fusion for a lumbar disc herniation in National Hockey League athletes.
AB  - BACKGROUND: Ice hockey players have a high incidence of lumbar spine disorders;
      however, there is no evidence in the literature to guide the treatment of an ice
      hockey player with a herniated lumbar disc. PURPOSE: To determine the performance
      based outcomes in professional National Hockey League (NHL) athletes with a
      lumbar disc herniation after either nonsurgical or surgical treatment. STUDY
      DESIGN: Descriptive epidemiological study. METHODS: Athletes in the NHL with a
      lumbar disc herniation were identified through team injury reports and archives
      on public record. The return-to-play rate, games played per season, points per
      game, and performance score for each player were determined before and after the
      diagnosis of a lumbar disc herniation. Statistical analysis was used to compare
      preinjury and postinjury performance measures for players treated with either
      nonsurgical or surgical treatment. RESULTS: A total of 87 NHL players met the
      inclusion criteria; 31 underwent nonoperative care, 48 underwent a discectomy,
      and 8 underwent a single-level fusion. The return-to-play rate for all players
      was 85%. There was a significant decrease in performance in all players after a
      lumbar disc herniation in games played per season, points scored per game, and
      performance score. A comparison of the posttreatment results for the nonsurgical
      and surgical patient groups revealed no significant difference in performance
      measures. Notably, the lumbar fusion group did not show a decrease in games
      played per season or performance score after surgery, likely secondary to a small
      sample size. CONCLUSION: National Hockey League players with a lumbar disc
      herniation have a high return-to-play rate regardless of the type of treatment;
      however, performance-based outcomes may decrease compared with preinjury levels.
      The study data suggest that a lumbar fusion is compatible with a return to play
      in the NHL, which is in contrast to other professional sports.

PMID- 23956135
TI  - Role of arthropod communities in bioenergy crop litter decomposition?.
AB  - The extensive land use conversion expected to occur to meet demands for bioenergy
      feedstock production will likely have widespread impacts on agroecosystem
      biodiversity and ecosystem services, including carbon sequestration. Although
      arthropod detritivores are known to contribute to litter decomposition and thus
      energy flow and nutrient cycling in many plant communities, their importance in
      bioenergy feedstock communities has not yet been assessed. We undertook an
      experimental study quantifying rates of litter mass loss and nutrient cycling in
      the presence and absence of these organisms in three bioenergy feedstock crops
      miscanthus (Miscanthus x giganteus), switchgrass (Panicum virgatum), and a
      planted prairie community. Overall arthropod abundance and litter decomposition
      rates were similar in all three communities. Despite effective reduction of
      arthropods in experimental plots via insecticide application, litter
      decomposition rates, inorganic nitrogen leaching, and carbon-nitrogen ratios did
      not differ significantly between control (with arthropods) and treatment (without
      arthropods) plots in any of the three community types. Our findings suggest that
      changes in arthropod faunal composition associated with widespread adoption of
      bioenergy feedstock crops may not be associated with profoundly altered arthropod
      mediated litter decomposition and nutrient release. 

PMID- 23956136
TI  - A new form of severe spondyloepimetaphyseal dysplasia: clinical and radiological
      characterization.
AB  - We report on two patients with a severe form of spondyloepimetaphyseal dysplasia
      (SEMD). Both patients show normal birth length, early postnatal growth
      deficiency, severe short stature, flexion contractures in the hips, bowing of the
      legs with genu varum. Skeletal radiographies show platyspondyly and
      characteristic vertebral body shape with central indentation of endplates,
      progressive, and severe metaphyseal changes, very small and irregular proximal
      femoral epiphyses with severe coxa vara, absence of calcifications, and mild
      metaphyseal irregularities in upper limbs. The similarities in the skeletal
      radiographs with SEMD type Strudwick and SEMD matrilin 3 type prompted us to
      analyze the COL2A1 and MATN3 genes. Direct sequencing of genomic DNA failed to
      identify any mutation in COL2A1 for both patients and MATN3 sequencing for
      Patient 1 identified only one heterozygous variant with no predicted damaging
      effect inherited from an unaffected parent. We therefore conclude that this form
      of SEMD probably differs from SEMD matrilin 3 type and does not belong to the
      spectrum of type II collagenopathies. The similarities between our two patients
      allowed us to propose that they might show a new form of SEMD.

PMID- 23956137
TI  - Increasing trends in Schedule II opioid use and doctor shopping during 1999-2007
      in California.
AB  - PURPOSE: To examine the age and gender-specific trends of Schedule II opioid use
      among California residents, with special reference to multiple provider users
      (doctor shoppers). METHODS: Utilizing data from the California Prescription Drug
      Monitoring Program, we examined age and gender-specific trends of Schedule II
      opioid use during calendar years 1999-2007. Specifically, we analyzed the
      following: (1) the prevalence of Schedule II opioid users among California's
      population and (2) the proportion of these opioid users who were doctor shoppers
      (defined as an individual who used more than five different prescribers for all
      Schedule II opioids he or she obtained in a calendar year). RESULTS: Among all
      age and gender groups, the prevalence of Schedule II opioid users in California
      increased by 150%-280% and the prevalence of doctor shoppers among users
      increased by 111%-213% over 9 years. The prevalence of opioid users was lowest
      among 18-44 year old men (1.25%) and highest among 65-year and older women
      (5.31%) by 2007. The prevalence of doctor shoppers was approximately 1.4% among
      those up to age 64 years and 0.5% among those 65 years and older. The gender
      difference in doctor shoppers among all age groups was negligible. On average,
      the cumulative morphine-equivalent amount of Schedule II opioid per individual
      obtained per year was threefold to sixfold higher for doctor shoppers than for
      the general population across different age and gender groups. CONCLUSIONS: Age
      and gender differences in opioid use were relatively small, whereas the trends
      for use of opioids and multiple providers grew at a disquieting rate.

PMID- 23956138
TI  - Characterization of the EGFR interactome reveals associated protein complex
      networks and intracellular receptor dynamics.
AB  - Growth factor receptor mediated signaling is meanwhile recognized as a complex
      signaling network, which is initiated by recruiting specific patterns of adaptor
      proteins to the intracellular domain of epidermal growth factor receptor (EGFR).
      Approaches to globally identify EGFR-binding proteins are required to elucidate
      this network. We affinity-purified EGFR with its interacting proteins by
      coprecipitation from lysates of A431 cells. A total of 183 proteins were
      repeatedly detected in high-resolution MS measurements. For 15 of these, direct
      interactions with EGFR were listed in the iRefIndex interaction database,
      including Grb2, shc-1, SOS1 and 2, STAT 1 and 3, AP2, UBS3B, and ERRFI. The newly
      developed Cytoscape plugin ModuleGraph allowed retrieving and visualizing 93 well
      described protein complexes that contained at least one of the proteins found to
      interact with EGFR in our experiments. Abundances of 14 proteins were modulated
      more than twofold upon EGFR activation whereof clathrin-associated adaptor
      complex AP-2 showed 4.6-fold enrichment. These proteins were further annotated
      with different cellular compartments. Finally, interactions of AP-2 proteins and
      the newly discovered interaction of CIP2A could be verified. In conclusion, a
      powerful technique is presented that allowed identification and quantitative
      assessment of the EGFR interactome to provide further insight into EGFR
      signaling. 

PMID- 23956139
TI  - Porcine small intestine submucosal graft for endoscopic skull base
      reconstruction.
AB  - BACKGROUND: Skull base defects and encephaloceles of the sinus and nasal cavities
      are routinely repaired endoscopically using a variety of materials including
      bone, cartilage, fascia, acellular dermal allografts, and xenografts, with high
      success rates. However, there is a paucity of data regarding the use of porcine
      small intestine submucosal (SIS) grafts for endoscopic dural repair. The purpose
      of the current study was to review outcomes using SIS grafts in the endoscopic
      reconstruction of skull base defects. METHODS: Review of prospectively collected
      data regarding skull base defect repair using SIS was performed. Demographics,
      location, and size of skull base defect, method of repair, successful closure,
      and complications were recorded. RESULTS: Over 4.5 years, 155 patients (mean age
      49 years) underwent 170 primary skull base repairs using porcine SIS. Etiologies
      included tumor (76), spontaneous (51), trauma (37), and congenital (5). The
      majority of repairs were in combination with a nasoseptal flap (n = 113). Average
      defect size (length vs width) was 13 * 10.5 mm. Success rate on first attempt was
      94.7% (161/170), and all defects were effectively sealed on subsequent endoscopic
      revision. The average follow-up was 77 weeks. Major postoperative complications,
      including recurrent cerebrospinal fluid (CSF) leak (9), meningitis (1),
      periorbital cellulitis (1), and invasive fungal sinusitis (1), occurred in 6.4%
      of individuals with no long-term sequelae. CONCLUSION: Use of porcine SIS dural
      graft was associated with excellent outcomes in this study and evidence presented
      here supports its routine use in the endoscopic closure of skull base defects.

PMID- 23956140
TI  - CYP1A1 and Cnr nitroreductase bioactivated niclosamide in vitro.
AB  - Niclosamide produces genotoxic effects, such as point mutations in Salmonella
      sp., sperm-head abnormalities in mice and clastogenic effects in human
      lymphocytes in vitro and in vivo. As cytochrome P450 could be involved in the
      bioactivation of niclosamide, we investigated which subfamily was involved. We
      used liver microsomal fractions from rats treated with phenobarbital/beta
      naphthoflavone (PB/beta-NF), benzo[a]pyrene (BaP) or cyclohexanol, which are
      known to induce different cytochrome P450 subfamilies, such as CYP2B, CYP1A1,
      CYP1A2 and CYP2E1. We also inhibited CYP1A and CYP2E using alpha-NF and
      diethyldithiocarbamate to identify the cytochrome P450 involved. Liver-S9
      fractions obtained from PB/beta-NF- and BaP-treated rats significantly increased
      the number of revertants induced by niclosamide, while the CYP1A1 inhibitor alpha
      NF decreased the number of revertants. The incubation of niclosamide with CYP1A1
      SupersomesTM increased the number of revertants, suggesting that CYP1A1 is
      responsible for the bioactivation of niclosamide. Nitroreduction is also involved
      in niclosamide bioactivation, as the nitroreductase-deficient strain YG7132 did
      not respond to the niclosamide treatment. Our findings indicated that a
      metabolite, derived from the action of CYP1A1 and a nitroreduction-reaction
      process, has a key role in the bioactivation of niclosamide. 

PMID- 23956141
TI  - Reaction of amines with 8-methylthioBODIPY: dramatic optical and laser response
      to amine substitution.
AB  - A thorough study of the photophysical and laser properties of 8-aminoboron
      dipyrromethene dyes was undertaken to determine the role of amine substitution
      and spatial disposition on the properties of the dyes. It was found that the
      fluorescent and laser response varied significantly. Although primary amines give
      rise to highly fluorescent products at the blue edge of the visible region,
      secondary amines yield nonfluorescent analogues in polar media. The crystal
      structures of two analogues are reported and described. Steric hindrance and the
      higher electron-releasing ability of the amine favor the formation of a quenching
      intramolecular charge-transfer state. Accordingly, boron dipyrromethene
      derivatives with primary amines exhibited laser emission with efficiencies of up
      to 44%. Besides, the more efficient derivative was also the most photostable,
      leading to a significant improvement in the lasing performance with regard to
      previously reported 8-aminoboron dipyrromethene derivatives. An increase in the
      solvent polarity, and mainly the presence of tertiary cyclic amines, led to a
      dramatic decrease or even the loss of the laser action.

PMID- 23956142
TI  - Drosophila melanogaster as a model system of aluminum toxicity and aging.
AB  - The aim of this study was to investigate the toxic effects of aluminum (Al) on
      the model organism-Drosophila melanogaster. The study is especially concerned
      with the effects of aluminum on the fruit fly's development, life span, and
      circadian rhythm in rest and activity. Flies were exposed to aluminum in
      concentrations from 40 to 280 mg/kg in rearing media or the flies were raised on
      control medium. Moreover, the life span of insects exposed to aluminum containing
      40, 120, or 240 mg/kg of Al in the medium, only during their larval development,
      during the whole life cycle and only in their adult life was tested. To check if
      aluminum and aging cause changes in D. melanogaster behavior, the locomotor
      activity of flies at different ages was recorded. Results showed that aluminum is
      toxic in concentrations above 160 mg/kg in the rearing medium. Depending on Al
      concentration and time of exposure, the life span of the flies was shortened. At
      intermediate concentrations (120 mg/kg), however, Al had a stimulating effect on
      males increasing their life span and level of locomotor activity. At higher
      concentration the aluminum exposure increased or decreased the level of locomotor
      activity of D. melanogaster depending on age of flies. In addition, in the oldest
      insects reared on aluminum supplemented media and in mid-aged flies reared on the
      highest concentration of Al the daily rhythm of activity was disrupted.

PMID- 23956143
TI  - Synthesis and determination of the absolute configuration of cavicularin by a
      symmetrization/asymmetrization approach.
AB  - Taking the strain: The asymmetric total synthesis and stereochemical assignment
      of (-)-cavicularin, which features a highly strained polycyclophane ring system,
      has been achieved. The key features of this synthesis are 1) macrocyclization by
      an SN Ar reaction, 2) group-selective reaction to induce planar chirality in a
      highly stereoselective manner, and 3) radical transannulation to construct the
      highly strained ring system.

PMID- 23956144
TI  - Influence of cornicle droplet secretions of the cabbage aphid, Brevicoryne
      brassicae, on parasitism behavior of naive and experienced Diaeretiella rapae.
AB  - Insects have evolved amazing methods of defense to ward off enemies. Many aphids
      release cornicle secretions when attacked by predators and parasitoids. These
      secretions contain an alarm pheromone that alerts other colony members of danger,
      thereby providing indirect fitness benefits to the releaser. In addition, contact
      with cornicle secretions could also threaten an attacker and could provide direct
      fitness to the releaser. However, cornicle secretions may also be recruited as a
      kairomonal cue by aphid natural enemies. In this study, we investigated the
      effect of the cornicle droplet volatiles of the cabbage aphid, Brevicoryne
      brassicae (L.), on the host-searching behavior of naive and experienced female
      Diaeretiella rapae (M(') Intosh) parasitoids in olfactometer studies. In
      addition, we evaluated the role of B. brassicae cornicle droplets on the
      oviposition preference of the parasitoid in a two-choice bioassay. Naive females
      did not exhibit any preference between volatiles from aphids secreting cornicle
      droplets over non-secreting aphids, while experienced parasitoids exploited the
      secretions in their host location. Experienced females were also able to choose
      volatiles from both secreting and non-secreting aphids over clean air, while this
      ability was not observed in naive females. Although secretion of cornicle
      droplets did not influence the percentage of first attack in either naive or
      experienced females, the success of attack (i.e. resulting in a larva) was
      significantly different between secreting and non-secreting aphids in the case of
      experienced parasitoids. 

PMID- 23956145
TI  - Phase I study of vinblastine and sirolimus in pediatric patients with recurrent
      or refractory solid tumors.
AB  - BACKGROUND: The combination of vinblastine and mammalian target of rapamycin
      (mTOR) inhibitor sirolimus inhibits the growth of neuroblastoma xenografts
      through pro-apoptotic and anti-angiogenic mechanisms. This phase I study aimed to
      explore the safety and toxicity of this combination in pediatric patients with
      advanced solid tumors. PROCEDURE: Patients <=21 years of age with
      recurrent/refractory solid tumors (including CNS) were eligible. Sirolimus was
      administered daily by mouth or nasogastric (NG) tube, with doses adjusted to
      achieve a target trough concentration of 10-15 ng/ml, with weekly intravenous
      vinblastine (dose escalated 4-6 mg/m(2)/dose according to 3 + 3 phase I design).
      RESULTS: Fourteen patients were enrolled (median age 8.7 years; range 2.3-19) of
      whom 12 were evaluable for toxicity and 11 for response. One patient experienced
      a dose-limiting toxicity (grade 3 mucositis) at the highest vinblastine dose
      level. Myelosuppression was the most common toxicity. Dose-adjusted sirolimus
      trough concentrations were significantly lower in patients receiving drug via NG
      tube (1.50 +/- 0.75 ng/ml/mg vs. 2.25 +/- 1.07 ng/ml/mg for oral administration).
      Correlative biomarker analysis demonstrated a significant reduction in serum
      concentration of soluble vascular endothelial growth factor receptor (sVEGFR2) at
      28 days compared to baseline consistent with inhibition of angiogenesis. One
      patient had a partial response and three had stable disease for more than 3
      months. CONCLUSIONS: The combination of mTOR inhibitor and vinblastine given over
      an extended continuous schedule is safe, associated with a reduction in
      circulating angiogenic factor (CAF) VEGFR2 and resulted in clinical responses.
      Future studies using the intravenously administered mTOR inhibitor temsirolimus
      are planned.

PMID- 23956146
TI  - Characterization of a beta-1,3-glucan recognition protein from the beet armyworm,
      Spodoptera exigua (Insecta: Lepidoptera: Noctuidae).
AB  - The beta-1,3-glucan recognition protein gene from Spodoptera exigua (SebetaGRP)
      was cloned and characterized. The cDNA of this gene is 1 644 nucleotides in
      length and the predicted polypeptide is 491 amino acids (aa) in length, with a
      calculated molecular mass of 54.8 kDa. The first 22 aa encode a predicted
      secretion signal peptide. A BLAST search, multiple sequence alignment, and
      phylogenetic analysis of the aa sequence of SebetaGRP revealed that this protein
      is most similar to the beta-1,3-glucan recognition protein (betaGRP) family of
      pattern recognition proteins. Using reverse-transcription polymerase chain
      reaction, we detected the presence of SebetaGRP transcripts in the egg, larval,
      pupal, and adult stages of S. exigua. In addition, the SebetaGRP transcript was
      expressed in all the tissues examined including the brain, hemocytes, fat body,
      intestine, and cuticle. There were no changes in SebetaGRP mRNA levels in larvae
      infected with ultraviolet (UV)-killed Escherichia coli DH5alpha compared with the
      control larvae inoculated with the water; however, SebetaGRP mRNA levels were
      markedly elevated 4-8 h after infection and slightly induced 12-24 h after
      infection in larvae injected with UV-killed Fusarium oxysporum. This may be
      because beta-1,3-glucan is the main component of the cell wall of F. oxysporum,
      but not E. coli DH5alpha. 

PMID- 23956147
TI  - Cost-offsets of prescription drug expenditures: data analysis via a copula-based
      bivariate dynamic hurdle model.
AB  - In this paper, we estimate a copula-based bivariate dynamic hurdle model of
      prescription drug and nondrug expenditures to test the cost-offset hypothesis,
      which posits that increased expenditures on prescription drugs are offset by
      reductions in other nondrug expenditures. We apply the proposed methodology to
      data from the Medical Expenditure Panel Survey, which have the following
      features: (i) the observed bivariate outcomes are a mixture of zeros and
      continuously measured positives; (ii) both the zero and positive outcomes show
      state dependence and inter-temporal interdependence; and (iii) the zeros and the
      positives display contemporaneous association. The point mass at zero is
      accommodated using a hurdle or a two-part approach. The copula-based approach to
      generating joint distributions is appealing because the contemporaneous
      association involves asymmetric dependence. The paper studies samples categorized
      by four health conditions: arthritis, diabetes, heart disease, and mental
      illness. There is evidence of greater than dollar-for-dollar cost-offsets of
      expenditures on prescribed drugs for relatively low levels of spending on drugs
      and less than dollar-for-dollar cost-offsets at higher levels of drug
      expenditures.

PMID- 23956148
TI  - High pH reversed-phase chromatography as a superior fractionation scheme compared
      to off-gel isoelectric focusing for complex proteome analysis.
AB  - MS/MS is the technology of choice for analyzing complex protein mixtures.
      However, due to the intrinsic complexity and dynamic range present in higher
      eukaryotic proteomes, prefractionation is an important step to maximize the
      number of proteins identified. Off-gel IEF (OG-IEF) and high pH RP (Hp-RP) column
      chromatography have both been successfully utilized as a first-dimension peptide
      separation technique in shotgun proteomic experiments. Here, a direct comparison
      of the two methodologies was performed on ex vivo peripheral blood mononuclear
      cell lysate. In 12-fraction replicate analysis, Hp-RP resulted in more peptides
      and proteins identified than OG-IEF fractionation. Distributions of peptide pIs
      and hydropathy did not reveal any appreciable bias in either technique.
      Resolution, defined here as the ability to limit a specific peptide to one
      particular fraction, was significantly better for Hp-RP. This leads to a more
      uniform distribution of total and unique peptides for Hp-RP across all fractions
      collected. These results suggest that fractionation by Hp-RP over OG-IEF is the
      better choice for typical complex proteome analysis.

PMID- 23956150
TI  - Autism and epistemology IV: Does autism need a theory of mind?
AB  - In their article, "Does the autistic child have a 'theory of mind'?," Baron-Cohen
      et al. [1985] proposed a novel paradigm to explain social impairment in children
      diagnosed as autistic (AD). Much research has been undertaken since their article
      went to print. The purpose of this commentary is to gauge whether Theory of Mind
      (ToM)-or lack thereof-is a valid model for explaining abnormal social behavior in
      children with AD. ToM is defined as "the ability to impute mental states to
      oneself and to others" and "the ability to make inferences about what other
      people believe to be the case." The source for their model was provided by an
      article published earlier by Premack and Woodruff, "Does the chimpanzee have a
      theory of mind?" Later research in chimpanzees did not support a ToM in primates.
      From the outset, ToM as a neurocognitive model of autism has had many
      shortcomings-methodological, logical, and empirical. Other ToM assumptions, for
      example, its universality in all children in all cultures and socioeconomic
      conditions, are not supported by data. The age at which a ToM emerges, or events
      that presage a ToM, are too often not corroborated. Recent studies of mirror
      neurons, their location and interconnections in brain, their relationship to
      social behavior and language, and the effect of lesions there on speech, language
      and social behavior, strongly suggests that a neurobiological as opposed to
      neurocognitive model of autism is a more parsimonious explanation for the social
      and behavioral phenotypes observed in autism.

PMID- 23956152
TI  - Jasmonate- and salicylate-induced defenses in wheat affect host preference and
      probing behavior but not performance of the grain aphid, Sitobion avenae.
AB  - Jasmonate- and salicylate-mediated signaling pathways play significant roles in
      induced plant defenses, but there is no sufficient evidence for their roles in
      monocots against aphids. We exogenously applied methyl jasmonate (MeJA) and
      salicylic acid (SA) on wheat seedlings and examined biochemical responses in
      wheat and effects on the grain aphid, Sitobion avenae (Fab.). Application of MeJA
      significantly increased levels of wheat's polyphenol oxidase, peroxidase and
      proteinase inhibitor 1, 2 and 6 days after treatment. In two-choice tests, adult
      aphids preferred control wheat leaves to MeJA- or SA-treated leaves. Electrical
      penetration graph (EPG) recordings of aphid probing behavior revealed that on
      MeJA-treated plants, the duration of aphid's first probe was significantly
      shorter and number of probes was significantly higher than those on control
      plants. Also total duration of probing on MeJA-treated plants was significantly
      shorter than on control plants. Total duration of salivation period on SA-treated
      plants was significantly longer, while mean phloem ingestion period was
      significantly shorter than on control plants. However, no significant difference
      in total duration of phloem sap ingestion period was observed among treatments.
      The EPG data suggest that MeJA-dependent resistance factors might be due to
      feeding deterrents in mesophyll, whereas the SA-mediated resistance may be phloem
      based. We did not observe any significant difference of MeJA and SA application
      on aphid development, daily fecundity, intrinsic growth rate and population
      growth. The results indicate that both MeJA- and SA-induced defenses in wheat
      deterred S. avenae colonization processes and feeding behavior, but had no
      significant effects on its performance. 

PMID- 23956151
TI  - Prediction of glycan motifs using quantitative analysis of multi-lectin binding:
      Motifs on MUC1 produced by cultured pancreatic cancer cells.
AB  - PURPOSE: Lectins are valuable tools for detecting specific glycans in biological
      samples, but the interpretation of the measurements can be ambiguous due to the
      complexities of lectin specificities. Here, we present an approach to improve the
      accuracy of interpretation by converting lectin measurements into quantitative
      predictions of the presence of various glycan motifs. EXPERIMENTAL DESIGN: The
      conversion relies on a database of analyzed glycan array data that provides
      information on the specificities of the lectins for each of the motifs. We tested
      the method using measurements of lectin binding to glycans on glycan arrays and
      then applied the method to predicting motifs on the protein mucin 1 (MUC1)
      expressed in eight different pancreatic cancer cell lines. RESULTS: The combined
      measurements from several lectins were more accurate than individual measurements
      for predicting the presence or absence of motifs on arrayed glycans. The analysis
      of MUC1 revealed that each cell line expressed a unique pattern of glycoforms,
      and that the glycoforms significantly differed between MUC1 collected from
      conditioned media and MUC1 collected from cell lysates. CONCLUSIONS AND CLINICAL
      RELEVANCE: This new method could provide more accurate analyses of glycans in
      biological sample and make the use of lectins more practical and effective for a
      broad range of researchers.

PMID- 23956153
TI  - Human foreskin fibroblast-like stromal cells can differentiate into functional
      hepatocytic cells.
AB  - Foreskin fibroblast-like stromal cells (FDSCs) are progenitors isolated from
      human tissue that can differentiate into diverse cell types. Many types of stem
      cells can differentiate into hepatocyte-like cells, which could be used for drug
      testing or in liver regeneration therapy, but whether FDSCs can be converted into
      functional hepatocytes is unknown. FDSCs show divergent properties when cultured
      in distinct media, forming spheres in Dulbecco's modified Eagle's medium (DMEM)
      containing F12, epidermal growth factor (EGF), and basic fibroblast growth factor
      (b-FGF), but have fibroblast-like morphology when cultured in DMEM-based growth
      medium. Both cell populations express the typical mesenchymal stem cell markers
      CD90, CD105, and CD73, but the p75 neurotrophin receptor (p75NTR) was detected
      only in FDSC spheres. Both types of FDSCs can differentiate into hepatocyte-like
      cells, which express typical liver markers, including albumin and hepatocyte
      paraffin 1 (Hep Par1), along with liver-specific biological activities. When
      plasmids containing the human hepatitis B virus (HBV) genome were transfected
      transiently into FDSCs, differentiated hepatocyte-like cells secrete large
      amounts of HBe and HBs antigens. FDSCs could be used for clinical hepatic therapy
      and/or serve as a model of HBV. 

PMID- 23956154
TI  - A prescription for unemployment? Recessions and the demand for mental health
      drugs.
AB  - We estimate the relationship between mental health drug prescriptions and the
      level of labor market activity in the USA. Based on monthly data from the
      National Ambulatory Medical Care Survey of physicians and aggregated by US census
      regions, we find that the number of mental health drug prescriptions (those aimed
      at alleviating depression and anxiety) rises by about 10% when employment falls
      by 1% and when unemployment rises by 100 basis points, but only for patients in
      the Northeast region. This paper is one of the first to look at compensatory
      health behavior in response to the business cycle.

PMID- 23956155
TI  - Effects of photoperiod and temperature on diapause induction in Conogethes
      punctiferalis (Lepidoptera: Pyralidae).
AB  - The yellow peach moth, Conogethes punctiferalis (Guenee), a multivoltine species
      that overwinters as diapausing larvae, is one of the most serious insect pests on
      maize in China. Effect of photoperiod and temperature on larval diapause was
      examined under empirical laboratory conditions. Short-day treatments caused
      larval diapause at 25 degrees C, and the critical photoperiod was between 12 and
      13 h (or 12 h 51 min) light per day. No sensitive instar was identified for
      diapause induction under alternated short- (L : D 11 : 13 h) and long-day (L : D
      14 : 10 h) treatments at different larval stages. However, accumulative treatment
      of three instars and 10 d under short-day treatment was required for the
      induction of 50% larval diapause. All larvae entered diapause at 20 degrees C,
      whereas less than 3% did so at 30 degrees C, irrespective of the long- or short
      day treatment. Furthermore, under the short-day treatment, more than 90% of
      larvae went into diapause with temperatures <= 25 degrees C, but less than 17%
      did so at 28 degrees C. In contrast, under the long-day treatment, less than 19%
      of larvae went into diapause with temperatures >= 23 degrees C. The forward shift
      (5 degrees C) of critical temperature under the long-day regime demonstrated the
      compensatory effect of temperature and photoperiod on diapause induction. In
      conclusion, C. punctiferalis had a temperature-dependent type I photoperiodic
      diapause response; there was no sensitive instar for diapause determination, but
      the photoperiodic accumulation time countermeasures both of the short-day cycles
      and the number of instars exposed, and the photoperiodic diapause response, was a
      temperature-compensated phenomenon.

PMID- 23956156
TI  - Chronic high glucose induced INS-1beta cell mitochondrial dysfunction: a
      comparative mitochondrial proteome with SILAC.
AB  - As glucose-stimulated insulin secretion of pancreatic beta cell is triggered and
      promoted by the metabolic messengers derived from mitochondria, mitochondria take
      a central stage in the normal function of beta cells. beta cells in diabetics
      were chronically exposed to hyperglycemia stimulation, which have been reported
      to exert deleterious effects on beta-cell mitochondria. However, the mechanism of
      the toxic effects of hyperglycemia on beta-cell mitochondria was not clear. In
      this study, we characterized the biological functional changes of rat INS-1beta
      cells and their mitochondria with chronic exposure to hyperglycemia and created a
      research model of chronic hyperglycemia-induced dysfunctional beta cells with
      damaged mitochondria. Then, SILAC-based quantitative proteomic approach was used
      to compare the mitochondrial protein expression from high glucose treated INS
      1beta cells and control cells. The expression of some mitochondrial proteins was
      found with significant changes. Functional classification revealed most of these
      proteins were related with oxidative phosphorylation, mitochondrial protein
      biosynthesis, substances metabolism, transport, and cell death. These results
      presented some useful information about the effect of glucotoxicity on the beta
      cell mitochondria.

PMID- 23956157
TI  - Infectious complications in the first year following autologous hematopoietic
      progenitor cell rescue for children with brain tumors.
AB  - BACKGROUND: High-dose chemotherapy with autologous hematopoietic progenitor cell
      rescue (AuHPCR) for pediatric patients with brain tumors has become an important
      therapeutic modality to avoid or delay the long-term effects of cranial
      irradiation. Data on post-AuHPCR infectious complications in this population are
      lacking. This single institution retrospective review reports the prophylactic
      practices and infections in the first year following AuHPCR in pediatric patients
      with brain tumors. PROCEDURE: The medical record of patients who underwent AuHPCR
      for the treatment of a malignant brain tumor at Children's Hospital Los Angeles
      between 1988 and 2010 were reviewed. Patients without prior irradiation who were
      free of disease at 1 year without additional chemotherapy were evaluated for all
      infectious disease complications occurring from time of neutrophil engraftment to
      1 year post-AuHPCR. RESULTS: Forty-three of the 115 eligible patients were
      included. The median time to neutrophil engraftment was 11 days (range: 8-43
      days), and 20 Grade III/IV (no Grade V) infectious episodes developed in 15
      patients (35%). Fourteen episodes of bacteremia (70%) were catheter-related,
      predominantly gram-negative (71%), and polymicrobial (50%). There were no fungal
      or pneumocystis infections and only 1 of 25 (4%) at-risk patients developed VZV
      reactivation. CONCLUSIONS: These data suggest patients with brain tumors
      undergoing AuHPCR have few late-occurring non-catheter-related post-transplant
      infections indicating that prophylaxis practices were sufficient. Central lines
      should be removed soon after engraftment, but those with central line infections
      should receive adequate treatment including gram-negative coverage. In addition,
      only at-risk patients who receive further irradiation may benefit from VZV
      reaction prophylaxis.

PMID- 23956158
TI  - beta2-adrenergic receptor activation by agonists studied with 19F NMR
      spectroscopy.

PMID- 23956159
TI  - Effects of inspiratory muscle training on lung volumes, respiratory muscle
      strength, and quality of life in patients with ataxia telangiectasia.
AB  - BACKGROUND: Ataxia telangiectasia (AT) is a genetic syndrome caused by a mutation
      of chromosome 11. The clinical features are cerebellar ataxia, telangiectasia,
      and progressive loss of muscular coordination, including an inefficient cough
      secondary to progression of neurological disease. OBJECTIVE: To evaluate the
      effects of inspiratory muscle training (IMT) on ventilation, lung volume,
      dyspnoea, respiratory muscle strength, and quality of life in patients with AT.
      METHODS: A longitudinal study was conducted with 11 AT patients and nine healthy
      volunteers. Ventilometry, subjective sensation of dyspnoea, maximal inspiratory
      pressure (MIP), maximal expiratory pressure (MEP), and quality of life were
      assessed before and after a 24-week IMT program. The IMT load used was set at 60%
      of the MIP, and the training was performed for 20 min daily. RESULTS: Patients
      with AT had lower height and weight and also had lower respiratory muscle
      strength and lung volume compared with healthy volunteers. Furthermore, patients
      with AT showed a significant improvement when pre- and post-IMT were compared for
      ventilatory pattern: Vt (476.5 +/- 135 ml vs. 583.3 +/- 66 ml, P = 0.015) and f
      (23.3 +/- 6 rpm vs. 20.4 +/- 4 rpm, P = 0.018), and VC (1,664 +/- 463 ml/kg vs.
      2,145 +/- 750 ml/kg, P = 0.002). IMT also significantly improved the sensation of
      dyspnoea (median 0.5; minimum 0; maximum 1.0; P = 0.022) and respiratory muscle
      strength: MIP (-22.2 +/- 2 cmH2O vs. -38 +/- 9 cmH2O, P < 0.001) and MEP (29 +/-
      7 cmH2O vs. 40 +/- 8 cmH2O, P = 0.001). The health and vitality domains of the SF
      36 also showed significant improvement (P = 0.009 and P = 0.014, respectively)
      post-IMT. CONCLUSION: IMT was effective in improving ventilatory pattern, lung
      volume, respiratory muscle strength, and the health and vitality domains for
      quality of life in patients with AT. IMT may be an effective adjunct therapy to
      drug treatment for patients with AT.

PMID- 23956160
TI  - The current and future potential geographic range of West Indian fruit fly,
      Anastrepha obliqua (Diptera: Tephritidae).
AB  - The West Indian fruit fly, Anastrepha obliqua (Macquart), is one of the most
      important pests throughout the Americas. CLIMEX 3.0 and ArcGIS 9.3 were used to
      model the current and future potential geographical distribution of this pest.
      Under current climatic conditions, A. obliqua is predicted to be able to
      establish throughout much of the tropics and subtropics, including not only North
      and South America, where it has been reported, but also southern Asia,
      northeastern Australia and Sub-Saharan Africa. The main factors limiting the
      pest's range expansion may be cold stress. Climate change expands the potential
      distribution of A. obliqua poleward as cold stress boundaries recede, but the
      predicted distribution in northwestern Australia and northern parts of Sub
      Saharan Africa will decrease because of heat stress. Considering the widely
      suitable range for A. obliqua globally and in China, enhanced quarantine and
      monitoring measures should be implemented in areas that are projected to be
      suitable for the establishment of the pest under current and future climatic
      conditions.

PMID- 23956162
TI  - A cross-sectional study of mental health in UK veterinary undergraduates.
AB  - Wellbeing (positive mental health) and mental ill-health of veterinary students
      from a single UK school were quantified using validated psychological scales.
      Attitudes towards mental ill-health and suicide were also assessed. Results were
      compared with published data from the UK general population and veterinary
      profession. Of the total student population (N=1068), 509 (48 per cent) completed
      a questionnaire. Just over half (54 per cent) of the respondents had ever
      experienced mental ill-health, with the majority reporting a first occurrence
      before veterinary school. Student wellbeing was significantly poorer (p<0.0001)
      than general population estimates, but not significantly different (p=0.2) from
      veterinary profession estimates. Degree of mental distress in students was
      significantly higher than in the general population (p<0.0001). Despite the
      majority (94 per cent) agreeing that 'Anyone can suffer from mental health
      problems', students were significantly more likely than members of the general
      population to agree that 'If I were suffering from mental health problems, I
      wouldn't want people knowing about it' (p<0.0001). Students were more likely to
      have thought about suicide, but less likely to have made an attempt (p<0.001;
      p=0.005), than members of the general population. The possibility of non-response
      bias must be considered when interpreting findings. However, strong similarities
      between results from this study population and the UK veterinary profession, as
      well as other veterinary student populations internationally, suggest no
      substantial school-level bias. 

PMID- 23956161
TI  - Analysis of the APETALA3- and PISTILLATA-like genes in Hedyosmum orientale
      (Chloranthaceae) provides insight into the evolution of the floral homeotic B
      function in angiosperms.
AB  - BACKGROUND AND AIMS: According to the floral ABC model, B-function genes appear
      to play a key role in the origin and diversification of the perianth during the
      evolution of angiosperms. The basal angiosperm Hedyosmum orientale
      (Chloranthaceae) has unisexual inflorescences associated with a seemingly
      primitive reproductive morphology and a reduced perianth structure in female
      flowers. The aim of this study was to investigate the nature of the perianth and
      the evolutionary state of the B-function programme in this species. METHODS: A
      series of experiments were conducted to characterize B-gene homologues isolated
      from H. orientale, including scanning electron microscopy to observe the
      development of floral organs, phylogenetic analysis to reconstruct gene
      evolutionary history, reverse transcription-PCR, quantitative real-time PCR and
      in situ hybridization to identify gene expression patterns, the yeast two-hybrid
      assay to explore protein dimerization affinities, and transgenic analyses in
      Arabidopsis thaliana to determine activities of the encoded proteins. KEY
      RESULTS: The expression of HoAP3 genes was restricted to stamens, whereas HoPI
      genes were broadly expressed in all floral organs. HoAP3 was able to partially
      restore the stamen but not petal identity in Arabidopsis ap3-3 mutants. In
      contrast, HoPI could rescue aspects of both stamen and petal development in
      Arabidopsis pi-1 mutants. When the complete C-terminal sequence of HoPI was
      deleted, however, no or weak transgenic phenotypes were observed and
      homodimerization capability was completely abolished. CONCLUSIONS: The results
      suggest that Hedyosmum AP3-like genes have an ancestral function in specifying
      male reproductive organs, and that the activity of the encoded PI-like proteins
      is highly conserved between Hedyosmum and Arabidopsis. Moreover, there is
      evidence that the C-terminal region is important for the function of HoPI. Our
      findings indicate that the development of the proposed perianth in Hedyosmum does
      not rely on the B homeotic function.

PMID- 23956163
TI  - Improving wellbeing in the veterinary profession: recent advances and future
      challenges.

PMID- 23956164
TI  - Iron supplementation in HIV-infected Malawian children with anemia: a double
      blind, randomized, controlled trial.
AB  - BACKGROUND: It is unknown whether iron supplementation in human immunodeficiency
      virus (HIV)-infected children living in regions with high infection pressure is
      safe or beneficial. A 2-arm, double-blind, randomized, controlled trial was
      conducted to examine the effects of iron supplementation on hemoglobin, HIV
      disease progression, and morbidity. METHODS: HIV-infected Malawian children aged
      6-59 months with moderate anemia (hemoglobin level, 7.0-9.9 g/dL) were randomly
      assigned to receive 3 mg/kg/day of elemental iron and multivitamins (vitamins A,
      C, and D) or multivitamins alone for 3 months. Participants were followed for 6
      months. RESULTS: A total of 209 children were randomly assigned to treatment, and
      196 (93.8%) completed 6 months of follow-up. Iron supplementation was associated
      with greater increases in hemoglobin concentrations (adjusted mean difference
      [aMD], 0.60; 95% confidence interval [CI], .06-1.13; P = .03) and reduced the
      risk of anemia persisting for up to 6 months follow-up (adjusted prevalence
      ratio, 0.59; 95% CI, .38-.92; P = .02). Children who received iron had a better
      CD4 percentage response at 3 months (aMD, 6.00; 95% CI, 1.84-10.16; P = .005) but
      an increased incidence of malaria at 6 months (incidence rate, 120.2 vs 71.7;
      adjusted incidence rate ratio [aIRR], 1.81 [95% CI, 1.04-3.16]; P = .04),
      especially during the first 3 months (incidence rate, 78.1 vs 36.0; aIRR, 2.68
      [95% CI, 1.08-6.63]; P = .03). CONCLUSIONS: Iron supplementation in anemic HIV
      infected children has beneficial effects on hemoglobin, anemia, and immunity but
      increases the risk of malaria. Thus, iron supplementation in HIV-infected
      children living in malaria-endemic areas should only be provided in combination
      with adequate protection from malaria. CLINICAL TRIALS REGISTRATION: ISRCTN
      62947977.

PMID- 23956165
TI  - Reduced risk of pertussis in whole-cell compared to acellular vaccine recipients
      is not supported when data are stratified by age.

PMID- 23956166
TI  - Complex interactions of HIV infection, malaria, and iron deficiency.

PMID- 23956167
TI  - Detection of cytomegalovirus DNA in plasma as an adjunct diagnostic for
      gastrointestinal tract disease in kidney and liver transplant recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) disease is the most common infectious
      complication after solid organ transplantation, frequently affecting the
      gastrointestinal (GI) tract. There are limited data on quantitative polymerase
      chain reaction (qPCR) for plasma CMV DNA as an adjunct diagnostic method for GI
      tract disease in kidney and liver transplant recipients. METHODS: We reviewed all
      records of adult kidney and liver transplant recipients with a GI tract biopsy
      and plasma CMV qPCR result within 15 days of biopsy during a 6.5-year period at
      our center. CMV GI tract disease was defined as histopathologic evidence of CMV
      on biopsy by immunohistochemistry or visualization of inclusion bodies. RESULTS:
      GI tract biopsy and qPCR results were available for 81 kidney and liver
      transplant recipients; 20 cases of confirmed CMV GI tract disease were
      identified. Overall, the sensitivity of qPCR for diagnosing CMV GI tract disease
      was 85% (95% confidence interval [CI], 61%-96%), and the specificity was 95% (95%
      CI, 85%-99%). For CMV-seronegative recipients (R(-)) with CMV-seropositive donors
      (D(+)), the sensitivity of qPCR was 100% (95% CI, 59%-99%), and the specificity
      was 80% (95% CI, 30%-99%). The lowest sensitivity was observed in CMV D(+)/R(+)
      cases (72.7%; 95% CI, 39%-93%). The mean plasma CMV copy number in patients with
      GI tract disease was 3.84 log10 (38 334 copies/mL). CONCLUSIONS: Plasma CMV qPCR
      had good sensitivity and excellent specificity for CMV GI tract disease in kidney
      and liver transplant recipients. Its sensitivity was 100% in CMV D(+)/R(-) cases
      but 72.7% in CMV D(+)/R(+) cases. This variation in assay performance according
      to host serostatus may reflect differences in disease pathogenesis.

PMID- 23956168
TI  - Delayed seroconversion and rapid onset of lymphoproliferative disease after
      transmission of human T-cell lymphotropic virus type 1 from a multiorgan donor.
AB  - BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) screening of blood
      and organ donors is not mandatory in Germany because of its low prevalence (about
      7/100 000). An HTLV-1 transmission event caused by a multiple organ donor was
      investigated. Validity of diagnostic procedures and HTLV-1 disease association in
      immunosuppressed organ recipients were analyzed. METHODS: Two screening
      immunoassays and an immunoblot (confirmatory assay) were used for detection of
      HLTV-1/2 antibodies. Proviral DNA was quantified in blood and biopsies of organ
      recipients by HTLV-1 real-time polymerase chain reaction (PCR). RESULTS: Proviral
      HTLV-1-DNA was detected in all blood samples of 3 organ recipients (1-100
      copies/10(2) cells), but seroconversion was delayed for up to 2 years in
      screening assays and >6 years in the confirmatory assay. In 2 of 3 organ
      recipients, a cutaneous T-cell lymphoma was diagnosed 2 and 3 years after
      infection, respectively. Proviral HTLV-1 DNA concentration was almost 100
      copies/10(2) cells in cutaneous lymphoma biopsies whereas in biopsies of other
      tissues <=3.0 copies/10(2) cells were found. The third organ recipient did not
      suffer from lymphoma, but detailed clinical data on this patient were not
      available to us. CONCLUSIONS: Biopsy results support an etiological role for HTLV
      1 in these cases of primary cutaneous T-cell lymphoma after solid organ
      transplant. HTLV-1-associated lymphoma can arise quickly in immunocompromised
      transplant recipients. The diagnosis of potentially HTLV-1-associated disease in
      organ recipients may require PCR because of delayed seroconversion.

PMID- 23956169
TI  - Effectiveness of nonadjuvanted monovalent influenza A(H1N1)pdm09 vaccines for
      preventing reverse transcription polymerase chain reaction-confirmed pandemic
      influenza hospitalizations: case-control study of children and adults at 10 US
      influenza surveillance network sites.
AB  - During 2009-2010, we examined 217 patients hospitalized with laboratory-confirmed
      pandemic influenza in 9 Influenza Hospitalization Surveillance Network sites and
      413 age- and community-matched controls and found that a single dose of
      monovalent nonadjuvanted influenza A(H1N1)pdm09 vaccine was 50% (95% confidence
      interval, 13%-71%) effective in preventing hospitalization associated with
      A(H1N1)pdm09 virus infection. 

PMID- 23956170
TI  - Reply to Andre et al.

PMID- 23956171
TI  - Diagnosis of gastrointestinal cytomegalovirus infections: an imperfect science.

PMID- 23956172
TI  - Editorial commentary: lessons on transplant-acquired human T-cell lymphotropic
      virus infection.

PMID- 23956173
TI  - JAG1 mutation in a patient with deletion 22q11.2 syndrome and tetralogy of
      Fallot.
AB  - Deletion 22q11.2 (del22q11.2) syndrome, also known as DiGeorge/Velo-cardio-facial
      syndrome (DG/VCFS), and Alagille syndrome are genetic disorders
      characteristically associated with congenital heart defects (CHDs). We report on
      a patient with tetralogy of Fallot (TOF) and clinical features of DG/VCFS,
      hemizygous for del22q11.2 and heterozygous for the 2810G > A (p.Arg937Gln)
      mutation in the JAG1 gene associated with Alagille syndrome. The clinical
      features of del22q11.2 syndrome are present in the patient, including facial
      anomalies, typical TOF, speech delay with hypernasal voice, and learning
      difficulties. TOF and mild hepatic involvement, consisting of slightly elevated
      aminotransferase conjugated bilirubin levels, were the only features of Alagille
      syndrome in our patient. The anatomic type of TOF displayed no distinctive
      recognizable pattern for either DG/VCFS or Alagille syndrome. It is likely that
      hemizygosity of the TBX1 gene was causally related to TOF in this patient,
      although a synergistic pathogenic role of the JAG1 gene mutation in causing the
      heart defect cannot be excluded. JAG1 mutations have been previously detected in
      patients with nonsyndromic TOF and recent molecular evidence supports the
      cumulative effect of multiple genetic defects in the etiology of human
      malformations. We hypothesize that a similar mechanism could be present in this
      patient with del22q11.2 syndrome associated with a JAG1 missense mutation acting
      as possible modifier factor for TOF.

PMID- 23956174
TI  - SYN2 is an autism predisposing gene: loss-of-function mutations alter synaptic
      vesicle cycling and axon outgrowth.
AB  - An increasing number of genes predisposing to autism spectrum disorders (ASDs)
      has been identified, many of which are implicated in synaptic function. This
      'synaptic autism pathway' notably includes disruption of SYN1 that is associated
      with epilepsy, autism and abnormal behavior in both human and mice models.
      Synapsins constitute a multigene family of neuron-specific phosphoproteins (SYN1
      3) present in the majority of synapses where they are implicated in the
      regulation of neurotransmitter release and synaptogenesis. Synapsins I and II,
      the major Syn isoforms in the adult brain, display partially overlapping
      functions and defects in both isoforms are associated with epilepsy and autistic
      like behavior in mice. In this study, we show that nonsense (A94fs199X) and
      missense (Y236S and G464R) mutations in SYN2 are associated with ASD in humans.
      The phenotype is apparent in males. Female carriers of SYN2 mutations are
      unaffected, suggesting that SYN2 is another example of autosomal sex-limited
      expression in ASD. When expressed in SYN2  knockout neurons, wild-type human Syn
      II fully rescues the SYN2 knockout phenotype, whereas the nonsense mutant is not
      expressed and the missense mutants are virtually unable to modify the SYN2
      knockout phenotype. These results identify for the first time SYN2  as a novel
      predisposing gene for ASD and strengthen the hypothesis that a disturbance of
      synaptic homeostasis underlies ASD. 

PMID- 23956176
TI  - Low level epifluorescent detection of nanoparticles and DNA on dielectrophoretic
      microarrays.
AB  - Common epifluorescent microscopy lacks the sensitivity to detect low levels of
      analytes directly in clinical samples, such as drug delivery nanoparticles or
      disease related DNA biomarkers. Advanced systems such as confocal microscopes may
      improve detection, but several factors limit their applications. This study now
      demonstrates that combining an epifluorescent microscope with a dielectrophoretic
      (DEP) microelectrode array device enables the detection of nanoparticles and DNA
      biomarkers at clinically relevant levels. Using DEP microarray devices,
      nanoparticles and DNA biomarkers are rapidly isolated and concentrated onto
      specific microscopic locations where they are easily detected by epifluorescent
      microscopy. In this study, 40nm nanoparticles were detected down to 2-3 * 10(3)
      /ul levels and DNA was detected down to the 200 pg/ml level. The synergy of
      epifluorescent microscopy and DEP microarray devices provides a new paradigm for
      DNA biomarker diagnostics and the monitoring of drug delivery nanoparticle
      concentrations.

PMID- 23956175
TI  - Armet/Manf and Creld2 are components of a specialized ER stress response provoked
      by inappropriate formation of disulphide bonds: implications for genetic skeletal
      diseases.
AB  - Mutant matrilin-3 (V194D) forms non-native disulphide bonded aggregates in the
      rER of chondrocytes from cell and mouse models of multiple epiphyseal dysplasia
      (MED). Intracellular retention of mutant matrilin-3 causes endoplasmic reticulum
      (ER) stress and induces an unfolded protein response (UPR) including the
      upregulation of two genes recently implicated in ER stress: Armet and Creld2.
      Nothing is known about the role of Armet and Creld2 in human genetic diseases. In
      this study, we used a variety of cell and mouse models of chondrodysplasia to
      determine the genotype-specific expression profiles of Armet and Creld2. We also
      studied their interactions with various mutant proteins and investigated their
      potential roles as protein disulphide isomerases (PDIs). Armet and Creld2 were up
      regulated in cell and/or mouse models of chondrodysplasias caused by mutations in
      Matn3 and Col10a1, but not Comp. Intriguingly, both Armet and Creld2 were also
      secreted into the ECM of these disease models following ER stress. Armet and
      Creld2 interacted with mutant matrilin-3, but not with COMP, thereby validating
      the genotype-specific expression. Substrate-trapping experiments confirmed Creld2
      processed PDI-like activity, thus identifying a putative functional role.
      Finally, alanine substitution of the two terminal cysteine residues from the A
      domain of V194D matrilin-3 prevented aggregation, promoted mutant protein
      secretion and reduced the levels of Armet and Creld2 in a cell culture model. We
      demonstrate that Armet and Creld2 are genotype-specific ER stress response
      proteins with substrate specificities, and that aggregation of mutant matrilin-3
      is a key disease trigger in MED that could be exploited as a potential
      therapeutic target. 

PMID- 23956177
TI  - Mutation in TTI2 reveals a role for triple T complex in human brain development.
AB  - Tel2-interacting proteins 1 and 2 (TTI1 and TTI2) physically interact with
      telomere maintenance 2 (TEL2) to form a conserved trimeric complex called the
      Triple T complex. This complex is a master regulator of phosphoinositide-3-kinase
      related protein kinase (PIKKs) abundance and DNA damage response signaling. Using
      a combination of autozygosity mapping and high-throughput sequencing in a large
      consanguineous multiplex family, we found that a missense c.1307T>A/p.I436N
      mutation in TTI2 causes a human autosomal recessive condition characterized by
      severe cognitive impairment, microcephaly, behavioral troubles, short stature,
      skeletal anomalies, and facial dysmorphic features. Immunoblotting experiment
      showed decreased amount of all Triple T complex components in the patient skin
      fibroblasts. Consistently, a drastically reduced steady-state level of all PIKKs
      tested was also observed in the patient cells. Combined with previous
      observations, these findings emphasises the role of the TTI2 gene in the etiology
      of intellectual disability and further support the role of PIKK signaling in
      brain development and functioning. 

PMID- 23956178
TI  - Sequential loss of genetic variation in flea beetle Agasicles hygrophila
      (Coleoptera: Chrysomelidae) following introduction into China.
AB  - The flea beetle (Agasicles hygrophila) was imported to Florida, USA and then
      introduced from Florida into China in 1987 as a biological control agent for the
      invasive plant alligator weed (Alternanthera philoxeroides). The initial beetle
      population was subsequently used for sequential introductions in other areas of
      China, but little is known about the genetic consequences of the introductions.
      In this study, the genetic diversity and population structure of five beetle
      populations, the source Florida population, three intentionally introduced China
      populations and one accidentally dispersed China population, were examined using
      amplified fragment length polymorphisms. The results showed a clear pattern of
      decreasing genetic diversity with the sequential introductions. The diversity was
      highest in the Florida population followed by the first introduction to Chongqing
      and then in Kunming and Fuzhou. The lowest diversity was found in the
      accidentally dispersed Guangzhou population that was first recorded in 1996. Both
      loci parameters and Nei's genetic diversity showed a high variation among these
      populations. Genetic differentiation among populations was further verified by
      the GST statistic (0.136-0.432). Beetles in Kunming had the highest gene flow
      with those in Guangzhou, and therefore lowest differentiation and closest genetic
      distance. These data show that sequential introduction influenced the genetic
      diversity of populations in China. Genetic diversity should be considered in
      planning introduction and long-term maintenance of populations. 

PMID- 23956182
TI  - Two mitochondrial haplotypes in Pterochloroides persicae (Hemiptera: Aphididae:
      Lachninae) associated with different feeding sites.
AB  - Pterochloroides persicae (Cholodkovsky) is an aphid species belonging to the
      subfamily Lachninae that uses different members of Rosaceae (specially Prunus
      spp.) as hosts. Partial sequences from the mitochondrial cytochrome c oxidase 1
      (COI) and the nuclear long-wave opsin genes were obtained for approximately 100
      P. persicae aphid individuals sampled from 34 colonies collected mainly in
      Tunisia and other Mediterranean locations. The variability found at the
      mitochondrial locus revealed the presence of two maternal haplotypes in the
      studied area that differed in a single nucleotide. The nuclear gene analyzed,
      however, failed to reveal any variability in this species. The variability found
      at the COI locus was related to the season of aphid sampling and with the site of
      feeding, with haplotype I mostly detected in samples collected in spring and
      summer on trunks and branches and haplotype II only detected in aphids collected
      in autumn on roots. The observed pattern of molecular variation suggests the
      presence of two clonal races of P. persicae coexisting in the studied area
      differentially adapted to conditions prevalent in the alternative seasons and/or
      to different feeding sites. 

PMID- 23956183
TI  - Breath stacking in children with neuromuscular disorders.
AB  - Respiratory muscle weakness in neuromuscular disorders (NMD) can lead to shallow
      breathing and respiratory insufficiency over time. Children with NMD often cannot
      perform maneuvers to recruit lung volume. In adults, breath stacking with a mask
      and one-way valve can achieve significantly increased lung volumes. To evaluate
      involuntary breath stacking (IBS) in NMD, we studied 23 children of whom 15 were
      cognitively aware and able to communicate verbally. For IBS, a one-way valve and
      pneumotachograph were attached to a face mask. Tidal volumes (Vt) and minute
      ventilation (VE ) were calculated from airflow over 30 sec before and after 15
      sec of expiratory valve closure. Six cooperative male subjects with Duchenne
      muscular dystrophy (DMD) participated in a subsequent comparison of IBS with
      voluntary breath stacking (VBS) and supported breath stacking (SBS). The average
      Vt in those studied with IBS was 277 ml (range 29-598 ml). The average increase
      in volume by stacking was 599 ml (range -140 to 2,916 ml) above Vt . The average
      number of stacked breaths was 4.5 (range 0-17). VE increased on average by 18%
      after stacking (P < 0.05, paired t-test). Oxygen saturation did not change after
      stacking. Four of the 23 children did not breath stack. Compared to IBS, VBS
      achieved similar volumes in the six subjects with DMD but SBS was more successful
      in those with greatest muscle weakness. IBS may achieve breath volumes of
      approximately three times Vt and may be particularly useful in non-cooperative
      subjects with milder degrees of respiratory muscle weakness.

PMID- 23956184
TI  - Cumulative cisplatin dose is not associated with event-free or overall survival
      in children with newly diagnosed average-risk medulloblastoma treated with
      cisplatin based adjuvant chemotherapy: report from the Children's Oncology Group.
AB  - BACKGROUND: Survival rates for children with medulloblastoma have risen over the
      past decade, in part due to the addition of cisplatin-containing adjuvant
      chemotherapy. Total dose of cisplatin required for optimal treatment is unknown.
      The purpose of this study was to evaluate the survival outcomes based on
      cumulative cisplatin doses (CCD) in children with newly diagnosed average-risk
      medulloblastoma. PROCEDURE: CCD data were reviewed for 363 patients in a
      prospective study evaluating patients between 3 and 21 years with a newly
      diagnosed average-risk medulloblastoma and treated with craniospinal radiation
      and post-radiation cisplatin based adjuvant chemotherapy. RESULTS: Eight-year
      event-free survival (EFS) and overall survival (OS) estimates were 78.2 +/- 2.6%
      and 83.9 +/- 2.4%, respectively. Only 73 patients received the protocol specified
      CCD of 600 mg/m(2), primarily due to mandated cisplatin toxicity-related dose
      reductions. The median CCD given to those without relapse or death on treatment
      was 487.5 mg/m(2). CCD, as a time-dependent covariate, was not associated with
      EFS (P = 0.54) or OS (P = 0.11). The 343 patients who completed chemotherapy
      failure-free were categorized into four groups according to CCD (n = 10; 75-150
      mg/m(2)), (n = 26; 151-300 mg/m(2)), (n = 113; 301-450 mg/m(2)), and (n = 194;
      451-600 mg/m(2)). There were no statistically significant differences in
      distributions of EFS (P = 0.53) or OS (P = 0.49) among these four groups.
      CONCLUSION: CCD is not associated with EFS or OS suggesting that lower doses of
      cisplatin may be incorporated into future medulloblastoma trials, thereby
      limiting its toxicity profile without affecting survival. If ototoxicity is
      encountered, more stringent cisplatin dose modification/cessation rules seem
      warranted.

PMID- 23956185
TI  - Characterization of a cyclic nucleotide-activated K(+) channel and its lipid
      environment by using solid-state NMR spectroscopy.
AB  - Voltage-gated ion channels are large tetrameric multidomain membrane proteins
      that play crucial roles in various cellular transduction pathways. Because of
      their large size and domain-related mobility, structural characterization has
      proved challenging. We analyzed high-resolution solid-state NMR data on different
      isotope-labeled protein constructs of a bacterial cyclic nucleotide-activated
      K(+) channel (MlCNG) in lipid bilayers. We could identify the different
      subdomains of the 4*355 residue protein, such as the voltage-sensing domain and
      the cyclic nucleotide binding domain. Comparison to ssNMR data obtained on
      isotope-labeled cell membranes suggests a tight association of negatively charged
      lipids to the channel. We detected spectroscopic polymorphism that extends beyond
      the ligand binding site, and the corresponding protein segments have been
      associated with mutant channel types in eukaryotic systems. These findings
      illustrate the potential of ssNMR for structural investigations on large membrane
      embedded proteins, even in the presence of local disorder.

PMID- 23956186
TI  - The identification of MAFB mutations in eight patients with multicentric carpo
      tarsal osteolysis supports genetic homogeneity but clinical variability.
AB  - Multicentric carpo-tarsal osteolysis (MCTO) with or without nephropathy is a rare
      osteolysis disorder beginning in early childhood and involving mainly carpal and
      tarsal bones. Renal disease appears later in life in the majority of cases and
      evolves quickly to end stage renal failure. Autosomal dominant (AD) inheritance
      has been demonstrated, with a high frequency of sporadic cases. Recently,
      mutations in a highly conserved region of the MAFB gene (v-maf musculoaponeurotic
      fibrosarcoma oncogene ortholog B) have been identified in MCTO patients by exome
      sequencing. MafB, known as a regulator of various developmental processes, is
      essential for osteoclastogenesis and renal development. We report here the
      molecular screening of MAFB in eight MCTO patients from six families. We
      identified MAFB mutations in all, including three novel missense mutations
      clustering within the hot spot mutation region. Among the eight patients, six
      only presented renal disease. Our report confirms the genetic homogeneity of MCTO
      and provides data underlying the clinical variability of this disorder.

PMID- 23956188
TI  - Clinical applications of next-generation sequencing: the 2013 human genome
      variation society scientific meeting.
AB  - Next-generation sequencing (NGS) has significantly contributed to the
      transformation of genomic research by providing access to the genome for
      analysis, by significantly decreasing the sequencing costs and increasing the
      throughput. The next goal is to exploit this powerful technology in the clinic,
      namely for diagnostics and therapeutics. The 2013 annual meeting of the Human
      Genome Variation Society, held in Paris, France, provided a forum to discuss
      possible clinical applications of NGS, the potential of some of the current NGS
      systems to transition to the clinic, the identification of causative mutations
      for rare genetic disorders through whole-genome or targeted genome resequencing,
      the application of NGS for family genomics, and NGS data analysis tools. 

PMID- 23956187
TI  - The mitochondrial genome of the plant bug Apolygus lucorum (Hemiptera: Miridae):
      Presently known as the smallest in Heteroptera.
AB  - The complete mitochondrial (mt) genome of the plant bug, Apolygus lucorum, an
      important cotton pest, has been sequenced and annotated in this study. The entire
      circular genome is 14 768 bp in size and represents the smallest in presently
      known heteropteran mt genomes. The mt genome is encoding for two ribosomal RNA
      (rRNA) genes, 22 transfer RNA (tRNA) genes, 13 protein coding genes and a control
      region, and the order, content, codon usage and base organization show similarity
      to a great extent to the hypothetical ancestral model. All protein coding genes
      use standard initiation codons ATN. Conventional stop codons TAA and TAG have
      been assigned to the most protein coding genes; however, COIII, ND4 and ND5 genes
      show incomplete terminator signal (T). All tRNA genes possess the typical clover
      leaf structure, but the dihydrouridine arm of tRNA(Ser(AGN)) only forms a simple
      loop. Secondary structure models of rRNA genes are generally in accordance with
      the former models, although some differences exist in certain parts. Three
      intergenic spacers have never been found in sequenced mt genomes of Heteroptera.
      The phylogenetic study based on protein coding genes is largely congruent with
      previous phylogenetic work. Both Bayesian inference and maximum likelihood
      analyses highly support the sister relationship of A. lucorum and Lygus
      lineolaris, and Miridae presents a sister position to Anthocoridae.

PMID- 23956189
TI  - Sexual dimorphism in immune response: testing the hypothesis in an insect species
      with two male morphs.
AB  - It has been proposed that given that males should invest in sexual traits at the
      expense of their investment in immune response, females are better
      immunocompetent than males. Typically, this idea has been tested in monomorphic
      species, but rarely has been evaluated in polymorphic male species. We used
      Paraphlebia zoe, a damselfly with two male morphs: the black-winged morph (Black
      W) develop black spots as sexual traits and the hyaline-winged morph (Hyaline-W)
      resembles a female in size and wings color. We predicted that Black-W should have
      a lower immune response than Hyaline-W, but that the latter males should not
      differ from females in this respect. Nitric oxide (NO) and phenoloxidase (PO)
      production, as well as hemolymph protein content, were used as immune markers.
      Body size (wing length) was used as an indicator of the male condition. The
      results show that, as we predicted, females and Hyaline-W had higher values of NO
      than Black-W, corresponding to differences in size. However, the opposite was
      found in relation to PO production. Females had the highest levels of hemolymph
      protein content, whereas no differences were found between Black-W and Hyaline-W.
      These results partially support the sexual selection hypothesis and are discussed
      in the context of the life history of this species. Black-W, Hyaline-W, and
      females could express the immune markers that are prioritized by their particular
      condition, and probably neither of them could express all immune markers in an
      elevated manner, as this would result in an excessive accumulation of free
      radicals. 

PMID- 23956190
TI  - Silk fibroin/gelatin blend films crosslinked with enzymes for biomedical
      applications.
AB  - Microbial transglutaminase (mTG) and mushroom tyrosinase (MT) are used to
      crosslink B. mori silk fibroin/gelatin (SF/G) films. Crosslinked and
      uncrosslinked SF/G films show no phase separation. The thermal behavior and the
      conformational structure of SF/G films are strongly affected by blending and
      enzymatic treatment. Formation of high thermally stable crosslinked
      macromolecular species is observed, suggesting the occurrence of strong
      intermolecular interactions between the two polymers as confirmed by FT-Raman
      spectroscopy. Preliminary in vitro tests show that MT-crosslinked blends with G
      amounts >=40% and mTG-crosslinked SF/G 60/40 films support C2C12 cardiomyocyte
      adhesion and proliferation. 

PMID- 23956191
TI  - Evaluation of industrially applied heat-transfer fluids as liquid organic
      hydrogen carrier systems.
AB  - Liquid organic hydrogen carrier (LOHC) systems offer a very attractive method for
      the decentralized storage of renewable excess energy. In this contribution,
      industrially well-established heat-transfer oils (typically sold under trade
      names, e.g., Marlotherm) are proposed as a new class of LOHC systems. It is
      demonstrated that the liquid mixture of isomeric dibenzyltoluenes (m.p. -39 to 
      34  degrees C, b.p. 390  degrees C) can be readily hydrogenated to the
      corresponding mixture of perhydrogenated analogues by binding 6.2 wt% of H2. The
      liquid H2 -rich form can be stored and transported similarly to diesel fuel. It
      readily undergoes catalytic dehydrogenation at temperatures above 260  degrees C,
      which proves its applicability as a reversible H2 carrier. The presented LOHC
      systems are further characterized by their excellent technical availability at
      comparably low prices, full registration of the H2 -lean forms, and excellent
      thermal stabilities.

PMID- 23956192
TI  - Detection of aberrant methylation of 10 genes in genomic DNA of lung tumors.

PMID- 23956193
TI  - Red meat, Mediterranean diet and lung cancer risk among heavy smokers in the
      COSMOS screening study.
AB  - BACKGROUND: To assess whether intake of selected foods and food groups and
      adherence to a Mediterranean diet are associated with lung cancer risk in heavy
      smokers. PATIENTS AND METHODS: In the context of a lung cancer screening
      programme, we invited asymptomatic volunteers, aged 50 years or more, current
      smokers or recent quitters, who had smoked at least 20 pack-years, to undergo
      annual low-dose computed tomography. We assessed participants' diet at baseline
      using a self-administered food frequency questionnaire and calculated their
      average daily food intake using an ad hoc computer program and determined their
      alternate Mediterranean diet (aMED) score. We used Cox proportional hazards
      regression to assess the association between selected food items, beverages and
      the aMED score and lung cancer risk. RESULTS: During a mean screening period of
      5.7 years, 178 of 4336 participants were diagnosed with lung cancer. At
      multivariable analysis, red meat consumption was associated with an increased
      risk of lung cancer [hazard ratio (HR) Q4 versus Q1, 1.73; 95% confidence
      interval (CI) 1.15-2.61; P-value for trend 0.002], while tea consumption (HR for
      one or more cup/day versus none, 0.56; 95% CI 0.31-0.99; P-value for trend 0.04)
      and adherence to a Mediterranean diet (HR for aMED >= 8 versus <= 1, 0.10; 95% CI
      0.01-0.77) were significantly associated with reduced lung cancer risk.
      CONCLUSIONS: Among heavy smokers, high red meat consumption and low adherence to
      a Mediterranean diet are associated with increased risk of lung cancer.

PMID- 23956194
TI  - Expression analysis of chlorophyllid alpha binding protein, a secretory, red
      fluorescence protein in the midgut of silkworm, Bombyx mori.
AB  - Chlorophyllid alpha binding protein (chbp) was recently characterized by its
      ability to bind the prosthetic group of chlorophylls and little information is
      known regarding its expression. In the present study, we found that chpb was
      expressed highly and exclusively in the midgut of silkworm, Bombyx mori. The
      expression level of chbp was very high in the newly molted fifth instar larvae
      followed by gradual decline in the same instar. Our results demonstrated that
      CHBP was a secretory protein and located mainly in the apical of midgut
      epithelial cells. Real-time polymerase chain reaction analysis results showed
      that chpb highly expressed in the anterior midgut, threefold and sixfold higher
      compared with that of the middle midgut and posterior midgut, respectively, and
      chpb expression declined in darkness. In addition, the expression of chbp was
      affected by high-dose virus or bacterium infection. 

PMID- 23956196
TI  - Making cardiomyocytes: how mechanical stimulation can influence differentiation
      of pluripotent stem cells.
AB  - Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced
      pluripotent stem cells (iPSCs) have promise in regenerative medicine for a
      variety of applications. Their potential in the treatment of cardiovascular
      disease is of particular interest due to its severity and prevalence. In order to
      be successful for cell therapy, PSCs must be pre-differentiated into
      cardiomyocytes to prevent teratoma formation in vivo. Current methods focus on
      the supplementation of soluble factors to culture medium to drive differentiation
      into mesodermal lineages; however, these methods are costly with varying
      cardiomyocyte yields. Since cardiomyocytes are exposed to dynamic environments in
      vivo, there is potential in using mechanical stimulation to further drive
      differentiation in vitro. In this review, we will describe the most recent
      developments in how mechanical stimulation, including fluid shear, cyclic strain,
      and magnetically mediated strain, can guide cardiomyogenesis in PSCs.

PMID- 23956195
TI  - Substrate selection influences molecular recognition in a screen for lymphoid
      tyrosine phosphatase inhibitors.
AB  - Assay design is an important variable that influences the outcome of an inhibitor
      screen. Here, we have investigated the hypothesis that protein tyrosine
      phosphatase inhibitors with improved biological activity could be identified from
      a screen by using a biologically relevant peptide substrate, rather than
      traditional phosphotyrosine mimetic substrates. A 2000-member library of drugs
      and drug-like compounds was screened for inhibitors of lymphoid tyrosine
      phosphatase (LYP) by using both a peptide substrate (Ac-ARLIEDNE-pCAP-TAREG-NH2,
      peptide 1) and a small-molecule phosphotyrosine mimetic substrate (difluoromethyl
      umbelliferyl phosphate, DiFMUP). The results demonstrate that compounds that
      inhibited enzyme activity on the peptide substrate had greater biological
      activity than compounds that only inhibited enzyme activity on DiFMUP. Finally,
      epigallocatechin-3,5-digallate was identified as the most potent inhibitor of
      lymphoid tyrosine phosphatase activity to date, with an IC50 of 50 nM and
      significant activity in T-cells. Molecular docking simulations provided a first
      model for binding of this potent inhibitor to LYP; this will constitute the
      platform for ongoing lead optimization efforts.

PMID- 23956197
TI  - Chronic blood transfusion for primary and secondary stroke prevention in Nigerian
      children with sickle cell disease: a 5-year appraisal.
AB  - BACKGROUND: Chronic blood transfusion (CBT) diminishes the risk of primary and
      secondary stroke in sickle cell disease (SCD). We appraised CBT and assessed its
      feasibility as an option for stroke prevention in a setting of limited resources.
      METHODS: All new cases of SCD seen in the Paediatric Hematology/Neurology units
      of the University College Hospital, Ibadan, Nigeria over a 5-year period were
      screened and followed up to identify those who had an indication for CBT for
      stroke prevention. Caregivers were counseled and offered CBT when indicated.
      Children of caregivers who accepted chronic transfusion were carefully followed
      up and outcomes documented. RESULTS: Five (10%) of the caregivers of the 50
      children who had an indication for CBT for stroke prevention consented to the
      treatment. They all had homozygous sickle cell anemia and had suffered a stroke.
      None of the children with abnormal TCD velocities consented to CBT. Two children
      experienced transfusion reactions, fatal in one. The mean annual cost of chronic
      transfusion (without chelation) was $3,276 (SD = 1,168). Major reasons given for
      declining CBT were high costs of blood transfusion, unavailability of blood, the
      need to regularly seek for blood donors, and the indefinite duration of blood
      transfusions. CONCLUSION: High economic costs, unavailability of blood, need to
      regularly seek for blood donors, cultural beliefs, and high frequency of
      transfusion reactions are major challenges to a successful CBT program in
      Nigeria. There is a need for government subsidy on blood transfusions and
      improved efforts towards provision of safe and affordable blood.

PMID- 23956198
TI  - Dysregulation of FOXG1 pathway in a 14q12 microdeletion case.
AB  - "FOXG1 syndrome" includes postnatal microcephaly, severe intellectual disability
      with absence of language and agenesis of the corpus callosum. When the syndrome
      is associated with large 14q12q13 deletions, the patients present characteristic
      facial dysmorphism. Although all reports were based on genomic analysis, recently
      a FOXG1 regulatory elements deletion, associated with down regulated mRNA,
      suggested an implication of FOXG1 pathway. Herein, we report on a young boy with
      a phenotype consistent with a FOXG1 syndrome. He had a de novo translocation
      t(6;14)(q22.1;q12) associated with a heterozygous 14q12.2q13 deletion
      encompassing FOXG1. Subsequently, we investigated his transcriptomic profile on
      lymphoblastoid cell lines and/or fibroblasts and showed that FOXG1 was commonly
      down-regulated. Moreover, several other FOXG1 pathway genes were also disturbed.
      Our data and review of previous reports highlight dysregulation of FOXG1 pathway
      as the cause of the "FOXG1 syndrome" developmental disorder.

PMID- 23956199
TI  - Characterization and recombinant protein expression of ferritin light chain
      homologue in the silkworm, Bombyx mori.
AB  - The silkworm genome encodes three iron storage proteins or ferritins, Fer1HCH,
      Fer2LCH, and Fer3HCH. Probing our EST library constructed from 1-day-old silkworm
      eggs revealed only Fer2LCH mRNA, which encoded for a protein with a predicted
      putative N-glycosylation site. Developmental and tissue expression analyses
      during embryogenesis revealed that Fer2LCH mRNA was abundant from 6 h to 6 days
      after oviposition. Transcriptional expression of Fer2LCH during the postembryonic
      stage is also high in the larval fat body and mid-gut, and then is upregulated in
      all pupal tissues tested. We found that Fer2LCH mRNA contains an iron-responsive
      element, suggesting this ferritin subunit is subject to translational control.
      Although ferritin expression has been shown to increase following immune
      challenge in other insects, the levels of Fer2LCH mRNA were not significantly
      induced following viral or bacterial infection of Bombyx mori. Using a
      baculovirus expression system we expressed recombinant BmFer2LCH protein, which
      was detectable in the cytoplasmic fraction, likely in a compartment of the
      secretory pathway, and was shown to undergo posttranslational modifications
      including N-glycosylation. In particular, rBmFer2LCH carbohydrate chains were
      composed of mannose and GlcNAc. We suggest that Fer2LCH is important for iron
      homeostasis and maintaining normal organ function in silkworms.

PMID- 23956200
TI  - Thermosensitive macroporous cryogels functionalized with bioactive
      chitosan/bemiparin nanoparticles.
AB  - Thermosensitive macroporous scaffolds of poly(N-isopropylacrylamide) (polyNIPA)
      loaded with chitosan/bemiparin nanoparticles are prepared by the free radical
      polymerization in cryogenic conditions. Chitosan/bemiparin nanoparticles of 102
      +/- 6.5 nm diameter are prepared by complex coacervation and loaded into polyNIPA
      cryogels. SEM image reveal the highly porous structure of cryogels and the
      integration of nanoparticles into the macroporous system. Volume phase transition
      temperature (VPT) and total freezing water content of cryogels are established by
      differential scanning calorimetry, and their porosity is determined by image-NMR.
      Swelling of cryogels (above and below the VPT) is highly dependent on
      nanoparticles concentration. In vitro release profile of bemiparin from cryogel
      is highly modulated by the presence of chitosan. Bemiparin released from
      nanoparticles preserves its biological activity, as shown by the BaF32 cell
      proliferation assay. Cryogels are not cytotoxic for the human fibroblast cells
      and present excellent properties for application on tissue engineering and
      controlled release of heparin. 

PMID- 23956202
TI  - Simulating small-scale climate change effects-lessons from a short-term field
      manipulation experiment on grassland arthropods.
AB  - Climate change is expected to cause major consequences on biodiversity.
      Understanding species-specific reactions, such as species shifts, species
      declines, and changes in population dynamics is a key issue to quantify large
      scale impacts of climate change on biotic communities. As it is often impossible
      or at least impracticable to conduct large-scale experiments on biotic responses
      to climate change, studies at a smaller scale may be a useful alternative. In our
      study, we therefore tested responses of grassland arthropods (carabid beetles,
      spiders, grasshoppers) to simulated climate change in terms of species activity
      densities and diversity. We conducted a controlled field experiment by changing
      water and microclimatic conditions at a small scale (16 m(2) ). Roof
      constructions were used to increase drought-like conditions, whereas water supply
      was enhanced by irrigation. In all, 2 038 carabid beetles (36 species), 4 893
      spiders (65 species), and 303 Orthoptera (4 species) were caught using pitfall
      traps from May to August, 2010. During our experiment, we created an artificial
      small-scale climate change; and statistics revealed that these changes had short
      term effects on the total number of individuals and Simpson diversity of the
      studied arthropod groups. Moreover, our results showed that certain species might
      react very quickly to climate change in terms of activity densities, which in
      turn might influence diversity due to shifts in abundance patterns. Finally, we
      devised methodological improvements that may further enhance the validity of
      future studies. 

PMID- 23956201
TI  - Highly diverse protein library based on the ubiquitous (beta/alpha)8 enzyme fold
      yields well-structured proteins through in vitro folding selection.
AB  - Proper protein folding is a prerequisite for protein stability and enzymatic
      activity. Although directed evolution can be a powerful tool to investigate
      enzymatic function and to isolate novel activities, well-designed libraries of
      folded proteins are essential. In vitro selection methods are particularly
      capable of searching for enzymatic activities in libraries of trillions of
      protein variants, yet high-quality libraries of well-folded enzymes with such
      high diversity are lacking. We describe the construction and detailed
      characterization of a folding-enriched protein library based on the ubiquitous
      (beta/alpha)8 barrel fold, which is found in five of the six enzyme classes. We
      introduced seven randomized loops on the catalytic face of the monomeric,
      thermostable (beta/alpha)8 barrel of glycerophosphodiester phosphodiesterase
      (GDPD) from Thermotoga maritima. We employed in vitro folding selection based on
      protease digestion to enrich intermediate libraries containing three to four
      randomized loops for folded variants, and then combined them to assemble the
      final library (1014 DNA sequences). The resulting library was analyzed by using
      the in vitro protease assay and an in vivo GFP-folding assay; it contains ~1012
      soluble monomeric protein variants. We isolated six library members and
      demonstrated that these proteins are soluble, monomeric and show (beta/alpha)8
      barrel fold-like secondary and tertiary structure. The quality of the folding
      enriched library improved up to 50-fold compared to a control library that was
      assembled without the folding selection. To the best of our knowledge, this work
      is the first example of combining the ultra-high throughput mRNA display method
      with selection for folding. The resulting (beta/alpha)8 barrel libraries provide
      a valuable starting point to study the unique catalytic capabilities of the
      (beta/alpha)8 fold, and to isolate novel enzymes.

PMID- 23956203
TI  - Humidity and seasonality drives body size patterns in males of the bush cricket
      Isophya rizeensis Sevgili, 2003 (Orthoptera: Tettigoniidae: Phaneropterinae).
AB  - Two primary patterns of body size variation have been recorded in ectotherms in
      relation to latitudinal/altitudinal shifts. In some, body size increases with
      increasing latitude/altitude whereas, in others, body size decreases with
      increasing latitude/altitude. This clinal variation is generally assumed to be
      caused by local adaptation to environmental conditions however the selective
      variable(s) (temperature, humidity, diet quality, etc.) is still heavily debated.
      Here we investigate geographic variation in body size of dark and pale color
      morphs of males of the bush-cricket Isophya rizeensis collected from 15 locations
      along an elevation gradient ranging from 350 to 2 500 m. Using an information
      theoretical approach we evaluate the relative support of four different
      hypotheses (the temperature size rule, the moisture gradient hypothesis, the
      seasonal constraint hypothesis, and the primary productivity hypothesis)
      explaining body size variation along the altitudinal gradient. Body size
      variation in pale color morphs showed a curvilinear relationship with altitude
      while dark color morphs showed no variation in body size. Body size variation in
      pale color morphs was highly correlated with precipitation and temperature
      seasonality values thus giving strong support for the moisture gradient and
      seasonal constraint hypothesis. Our results reinforce the importance of gradients
      in humidity and seasonality over temperature in the creation of altitudinal body
      size clines and the role of selection for resistance to stress factors in the
      establishment of these clines. Whether a body size cline is observed or not might
      also depend on the phenotypic properties of the individuals, like coloration.

PMID- 23956204
TI  - Audiologic and vestibular assessment in patients with beta-thalassemia major
      receiving long-term transfusion therapy.
AB  - BACKGROUND: Life-long transfusion therapy with chelators is a treatment choice
      for patients with beta-thalassemia major. Some investigators have proposed
      auditory impairment related to the use of deferoxamine, but the mechanisms remain
      unclear and whether or not deferiprone has similar side effects needs to be
      evaluated. PROCEDURE: Thirty-seven patients with beta-thalassemia major who
      received regular transfusion in our hospital were enrolled. Chelation agents,
      including deferoxamine and deferiprone, were used. To assess audiologic function,
      otoscopy, pure tone audiometry (PTA), tympanometry, transient evoked oto-acoustic
      emission (TEOAE), and auditory brainstem response (ABR) were conducted. Bithermal
      caloric test was performed to evaluate vestibular function. RESULTS: All of the
      37 patients had normal findings on otoscopic evaluation and their tympanograms
      were type A. Thirteen patients (35.1%) had hearing impairment at one or more
      frequencies as detected by PTA. Compared to those without hearing impairment,
      patients with hearing impairment had lower serum ferritin levels (P = 0.01).
      Seven of 21 patients (33.3%) failed to pass the TEOAE, while 13 (61.9%) had
      abnormal ABR findings. Sixteen patients (80%) had canal paresis in the caloric
      test. CONCLUSIONS: The incidence of auditory impairment and vestibular
      dysfunction was high in patients with beta-thalassemia major receiving long-term
      transfusion therapy. Potential lesions of auditory impairment may exist anywhere
      along the auditory pathway, from the inner ear to the brainstem. Lower serum
      ferritin levels may be associated with hearing impairment. Therefore, regular
      check-ups of serum ferritin levels and periodic audiologic assessment are
      mandatory.

PMID- 23956205
TI  - Evidence for replicative mechanism in a CHD7 rearrangement in a patient with
      CHARGE syndrome.
AB  - Haploinsufficiency of CHD7 (OMIM# 608892) is known to cause CHARGE syndrome
      (OMIM# 214800). Molecular testing supports a definitive diagnosis in
      approximately 65-70% of cases. Most CHD7 mutations arise de novo, and no
      mutations affecting exon-7 have been reported to date. We report on an 8-year-old
      girl diagnosed with CHARGE syndrome that was referred to our laboratory for
      comprehensive CHD7 gene screening. Genomic DNA from the subject with a suspected
      diagnosis of CHARGE was isolated from peripheral blood lymphocytes and
      comprehensive Sanger sequencing, along with deletion/duplication analysis of the
      CHD7 gene using multiplex ligation-dependent probe amplification (MLPA), was
      performed. MLPA analysis identified a reduced single probe signal for exon-7 of
      the CHD7 gene consistent with potential heterozygous deletion. Long-range PCR
      breakpoint analysis identified a complex genomic rearrangement (CGR) leading to
      the deletion of exon-7 and breakpoints consistent with a replicative mechanism
      such as fork stalling and template switching (FoSTeS) or microhomology-mediated
      break-induced replication (MMBIR). Taken together this represents the first
      evidence for a CHD7 intragenic CGR in a patient with CHARGE syndrome leading to
      what appears to be also the first report of a mutation specifically disrupting
      exon-7. Although likely rare, CGR may represent an overlooked mechanism in
      subjects with CHARGE syndrome that can be missed by current sequencing and dosage
      assays.

PMID- 23956206
TI  - Designing cost-effective biopharmaceutical facilities using mixed-integer
      optimization.
AB  - Chromatography operations are identified as critical steps in a monoclonal
      antibody (mAb) purification process and can represent a significant proportion of
      the purification material costs. This becomes even more critical with increasing
      product titers that result in higher mass loads onto chromatography columns,
      potentially causing capacity bottlenecks. In this work, a mixed-integer nonlinear
      programming (MINLP) model was created and applied to an industrially relevant
      case study to optimize the design of a facility by determining the most cost
      effective chromatography equipment sizing strategies for the production of mAbs.
      Furthermore, the model was extended to evaluate the ability of a fixed facility
      to cope with higher product titers up to 15 g/L. Examination of the
      characteristics of the optimal chromatography sizing strategies across different
      titer values enabled the identification of the maximum titer that the facility
      could handle using a sequence of single column chromatography steps as well as
      multi-column steps. The critical titer levels for different ratios of upstream to
      dowstream trains where multiple parallel columns per step resulted in the removal
      of facility bottlenecks were identified. Different facility configurations in
      terms of number of upstream trains were considered and the trade-off between
      their cost and ability to handle higher titers was analyzed. The case study
      insights demonstrate that the proposed modeling approach, combining MINLP models
      with visualization tools, is a valuable decision-support tool for the design of
      cost-effective facility configurations and to aid facility fit decisions. 2013.

PMID- 23956207
TI  - Employing BAC-reporter constructs in the sea anemone Nematostella vectensis.
AB  - Changes in the expression and function of genes drive evolutionary change.
      Comparing how genes are regulated in different species is therefore becoming an
      important part of evo-devo studies. A key tool for investigating the regulation
      of genes is represented by bacterial artificial chromosomes (BAC)-reporter
      constructs. BACs are large insert libraries, often >100 kb, which thus capture
      the genomic sequences surrounding a gene of interest, including all, or nearly
      all, of the elements underpinning regulation. Recombinant BACs, containing a
      reporter gene in place of the endogenous coding sequence of genes, can be
      utilized to drive the expression of reporter genes under the regulatory control
      of the gene of interest while still embedded within its genomic context.
      Systematic deletions within the BAC-reporter construct can be used to identify
      the minimal reporter in an unbiased way, avoiding the risk of overlooking
      regulatory elements that may be many kilobases away from the transcription start
      site. Nematostella vectensis (Edwardsiidae, Anthozoa, Cnidaria) has become an
      important model in regenerative biology, ecology, and especially in studies of
      evo-devo and gene-regulatory networks due to its interesting phylogenetic
      position and amenability to molecular techniques. The increasing interest in this
      rising model system also led to a demand for methods that can be used to study
      the regulation of genes in Nematostella. Here, we present our progress in
      employing BAC-reporter constructs to visualize gene-expression in Nematostella.
      Using a new Nematostella-specific recombination cassette, we made nine different
      BAC-reporter constructs. Although five BAC recombinants gave variable effects,
      three constructs, namely Nv-bra:eGFP::L10 BAC, Nv-dpp:eGFP::L10 BAC, and Nv
      grm:eGFP::L10 BAC delivered promising results. We show that these three
      constructs express the reporter gene eGFP in 10.4-17.2% of all analyzed larvae,
      out of which 26.2-41.9% express GFP in a mosaic fashion within the expected
      domain. In addition to the expression within the known domains, we also observed
      cases of misexpression of eGFP and examples that could represent actual
      expression outside the described domain. Furthermore, we deep-sequenced and
      assembled five different BACs containing Nv-chordin, Nv-foxa, Nv-dpp, Nv-wnta,
      and Nv-wnt1, to improve assembly around these genes. The use of BAC-reporter
      constructs will foster cis-regulatory analyses in Nematostella and thus help to
      improve our understanding of the regulatory network in this cnidarian system.
      Ultimately, this will advance the comparison of gene-regulation across species
      and lead to a much better understanding of evolutionary changes and novelties. 

PMID- 23956208
TI  - Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and
      follow-up.

PMID- 23956209
TI  - Molecular cloning and characterization of a putative proline dehydrogenase gene
      in the Colorado potato beetle, Leptinotarsa decemlineata.
AB  - Leptinotarsa decemlineata adults exhibit a season-dependent activity. In spring,
      post-diapause beetles often fly a long distance from overwintering sites to
      potato fields. In summer and autumn, the flight ability is sharply reduced.
      Proline is the main energy substrate of L. decemlineata during flight and proline
      dehydrogenase (ProDH) catalyzes the first step in proline catabolism. Here we
      identified a putative LdProDH gene; it had three cDNA isoforms which shared the
      same 5'UTR and coding region, but differed in the lengths of 3'UTRs (515, 1 092
      and 1 242 bp for isoforms-1, -2 and -3, respectively). LdProDH encoded a 616
      amino acid protein that showed high sequence similarity to ProDH-like proteins
      from other insect species. LdProDH was expressed in the third and fourth instars
      larvae and adults, but not in pupae. Dietary ingestion of bacterially expressed
      LdProDH-dsRNA by adults significantly decreased its messenger RNA (mRNA) level,
      and caused an elevation of free proline content in the hemolymph. Further
      observation revealed that three canonical polyadenylation signals (AATAAA) were
      tandemly located in the 3'UTR of isoform-3. The first, second and third
      polyadenylation sites gave rise to isoforms-1, -2 and -3, respectively. Analysis
      of the genomic DNA uncovered that the three isoforms resulted from alternative
      polyadenylation. The mRNA level of isoform-1, which expressed at low levels in
      pre-diapause adults, became abundant in post-diapause beetles. It is indicated
      that the LdProDH expression is fine-tuned through 3'UTR to control proline
      catabolism for the season-dependent activity of L. decemlineata adults.

PMID- 23956210
TI  - Macrophage microRNA-155 promotes cardiac hypertrophy and failure.
AB  - BACKGROUND: Cardiac hypertrophy and subsequent heart failure triggered by chronic
      hypertension represent major challenges for cardiovascular research. Beyond
      neurohormonal and myocyte signaling pathways, growing evidence suggests
      inflammatory signaling pathways as therapeutically targetable contributors to
      this process. We recently reported that microRNA-155 is a key mediator of cardiac
      inflammation and injury in infectious myocarditis. Here, we investigated the
      impact of microRNA-155 manipulation in hypertensive heart disease. METHODS AND
      RESULTS: Genetic loss or pharmacological inhibition of the leukocyte-expressed
      microRNA-155 in mice markedly reduced cardiac inflammation, hypertrophy, and
      dysfunction on pressure overload. These alterations were macrophage dependent
      because in vivo cardiomyocyte-specific microRNA-155 manipulation did not affect
      cardiac hypertrophy or dysfunction, whereas bone marrow transplantation from wild
      type mice into microRNA-155 knockout animals rescued the hypertrophic response of
      the cardiomyocytes and vice versa. In vitro, media from microRNA-155 knockout
      macrophages blocked the hypertrophic growth of stimulated cardiomyocytes,
      confirming that macrophages influence myocyte growth in a microRNA-155-dependent
      paracrine manner. These effects were at least partly mediated by the direct
      microRNA-155 target suppressor of cytokine signaling 1 (Socs1) because Socs1
      knockdown in microRNA-155 knockout macrophages largely restored their hypertrophy
      stimulating potency. CONCLUSIONS: Our findings reveal that microRNA-155
      expression in macrophages promotes cardiac inflammation, hypertrophy, and failure
      in response to pressure overload. These data support the causative significance
      of inflammatory signaling in hypertrophic heart disease and demonstrate the
      feasibility of therapeutic microRNA targeting of inflammation in heart failure.

PMID- 23956211
TI  - Systemic hypertension in low-gradient severe aortic stenosis with preserved
      ejection fraction.
AB  - BACKGROUND: Low-gradient severe aortic stenosis with preserved ejection fraction
      is an increasingly recognized entity, and symptomatic patients may benefit from
      aortic valve replacement. However, systemic hypertension frequently coexists with
      low-gradient severe aortic stenosis, which itself may cause elevated left
      ventricular (LV) filling pressures with resultant symptoms of dyspnea. METHODS
      AND RESULTS: Symptomatic patients with hypertension (aortic systolic pressure
      >140 mm Hg) and low-gradient (mean gradient <40 mm Hg) severe aortic stenosis
      (aortic valve area <1 cm(2)) with preserved ejection fraction (ejection fraction
      >50%) who underwent invasive hemodynamic catheterization of the left and right
      sides of the heart received infusion of intravenous sodium nitroprusside to
      reduce blood pressure and arterial afterload. At baseline, patients had severe
      hypertension (aortic systolic pressure, 176+/-26 mm Hg), pulmonary hypertension
      (mean pressure, 39+/-12 mm Hg), elevated LV end-diastolic pressure (19+/-5 mm
      Hg), and reduced stroke volume (33+/-8 mL/m(2)). All measures of afterload were
      reduced with nitroprusside (P<0.001 for all). Nitroprusside reduced mean
      pulmonary artery pressure (25+/-10 mm Hg) and LV end-diastolic pressure (11+/-5
      mm Hg; P<0.001 for both compared with baseline). Aortic valve area (0.86+/-0.11
      to 1.02+/-0.16 cm(2); P=0.001) and mean gradient (27+/-5 to 29+/-6 mm Hg; P=0.02)
      increased with nitroprusside. CONCLUSIONS: Systemic hypertension in low-gradient
      severe aortic stenosis with preserved ejection fraction is associated with
      elevated LV filling pressures and pulmonary hypertension. Treatment of
      hypertension with vasodilator therapy results in a lowering of the total LV
      afterload, with a decrease in LV filling pressures and pulmonary artery
      pressures. These findings have important implications for the management of
      patients with low-gradient severe aortic stenosis with preserved ejection
      fraction and hypertension.

PMID- 23956212
TI  - Time to treat hypertension in patients with aortic stenosis.

PMID- 23956213
TI  - Distribution of the related weevil species Sitophilus oryzae and S. zeamais in
      Brazil.
AB  - The genus Sitophilus (Coleoptera: Curculionidae) encompasses species of great
      economic importance as stored grain pests worldwide. Among these species, the
      maize and the rice weevils (Sitophilus zeamais and Sitophilus oryzae,
      respectively) are particularly important in warmer climates. These two weevils
      exhibit closely morphological and ecological resemblance making difficult their
      proper identification and recognition of their distribution in grain-producing
      regions. Both species are recorded in South America and particularly in Brazil,
      but their respective distribution and prevalence were not yet assessed in the
      region. Therefore, several insect samples throughout Brazil were collected and
      subjected to morphological identification using male genitalia and also using
      molecular identification with species-specific primers designed for clear
      recognition of both the species. The primers were designed for the specific
      amplification of a gene fragment of the cytochrome oxidase subunit I, which
      exhibited high specificity during our preliminary experiments with insects from
      six populations of known species (either S. zeamais or S. oryzae). Both
      identification strategies provided the same results indicating prevalence of the
      maize weevil S. zeamais throughout the country. Two hypotheses may explain such
      prevalence: (i) the likely host preference of S. zeamais for maize because this
      is the most cultivated cereal in Brazil, and (ii) the prevalence of S. zeamais in
      tropical regions as compared with S. oryzae, which is more disseminated in
      subtropical and temperate regions. 

PMID- 23956214
TI  - Osteogenetic properties of electrospun nanofibrous PCL scaffolds equipped with
      chitosan-based nanoreservoirs of growth factors.
AB  - Bioactive implants intended for rapid, robust, and durable bone tissue
      regeneration are presented. The implants are based on nanofibrous 3D-scaffolds of
      bioresorbable poly-epsilon-caprolactone mimicking the fibrillar architecture of
      bone matrix. Layer-by-layer nanoimmobilization of the growth factor BMP-2 in
      association with chitosan (CHI) or poly-L-lysine over the nanofibers is
      described. The osteogenetic potential of the scaffolds coated with layers of CHI
      and BMP-2 is demonstrated in vitro, and in vivo in mouse calvaria, through
      enhanced osteopontin gene expression and calcium phosphate biomineralization. The
      therapeutic strategy described here contributes to the field of regenerative
      medicine, as it proposes a route toward efficient repair of bone defects at
      reduced risk and cost level. 

PMID- 23956215
TI  - Effects of destruxins on free calcium and hydrogen ions in insect hemocytes.
AB  - Destruxins, cyclohexadepsipeptidic mycotoxins isolated from the entomopathogenic
      fungus Metarhizium anisopliae, inhibit innate insect immunity. However, their
      mechanism of action remains unclear. In this study, the effects of destruxins on
      changes in free calcium and hydrogen ions in the hemocytes of Exolontha
      serrulata, Bombyx mori and the Spodoptera litura SL-1 cell line were detected
      using laser scanning confocal microscopy (LSCM). An instant Ca(2+) influx of
      hemocytes induced by destruxins A and B (DA and DB) was recorded. The DA/DB
      dependent Ca(2+) influx was not influenced by the Ca(2+) channel inhibitors 2
      aminoethoxydiphenyl borane (2-APB) and U73122. It also had an apparently
      different LSCM profile from that of the ionomycin-dependent Ca(2+) influx.
      However, the instant Ca(2+) influx was not seen in the SL-1 cells; on the
      contrary, a slow, moderate enhancement of intracellular Ca(2+) was observed.
      Meanwhile, an instant intracellular free H(+) decrease aroused by DA and DB was
      found. DB at 20 MUmol/L and DA at 690 MUmol/L significantly reduced intracellular
      free H(+) levels. Furthermore, the vacuolar H(+)-ATPase (V-ATPase) inhibitor
      bafilomycin A1 had obvious effects on the decreases of intracellular free H(+) in
      hemocytes. These results suggest that the mechanism of DA/DB-dependent Ca(2+)
      influx is perhaps not related to Ca(2+) channels and ionophores; rather, the
      intracellular free H(+) decrease might be due to V-ATPase inhibition.

PMID- 23956218
TI  - Identification and characterization of a hitherto unknown nucleotide-binding
      domain and an intricate interdomain regulation in HflX-a ribosome binding GTPase.
AB  - A role for HflX in 50S-biogenesis was suggested based on its similarity to other
      GTPases involved in this process. It possesses a G-domain, flanked by
      uncharacterized N- and C-terminal domains. Intriguingly, Escherichia coli HflX
      was shown to hydrolyze both GTP and adenosine triphosphate (ATP), and it was
      unclear whether G-domain alone would explain ATP hydrolysis too. Here, based on
      structural bioinformatics analysis, we suspected the possible existence of an
      additional nucleotide-binding domain (ND1) at the N-terminus. Biochemical studies
      affirm that this domain is capable of hydrolyzing ATP and GTP. Surprisingly, not
      only ND1 but also the G-domain (ND2) can hydrolyze GTP and ATP too. Further; we
      recognize that ND1 and ND2 influence each other's hydrolysis activities via two
      salt bridges, i.e. E29-R257 and Q28-N207. It appears that the salt bridges are
      important in clamping the two NTPase domains together; disrupting these unfastens
      ND1 and ND2 and invokes domain movements. Kinetic studies suggest an important
      but complex regulation of the hydrolysis activities of ND1 and ND2. Overall, we
      identify, two separate nucleotide-binding domains possessing both ATP and GTP
      hydrolysis activities, coupled with an intricate inter-domain regulation for
      Escherichia coli HflX. 

PMID- 23956219
TI  - Different functions for the domains of the Arabidopsis thaliana RMI1 protein in
      DNA cross-link repair, somatic and meiotic recombination.
AB  - Recombination intermediates, such as double Holliday junctions, can be resolved
      by nucleases or dissolved by the combined action of a DNA helicase and a
      topoisomerase. In eukaryotes, dissolution is mediated by the RTR complex
      consisting of a RecQ helicase, a type IA topoisomerase and the structural protein
      RecQ-mediated genome instability 1 (RMI1). Throughout eukaryotes, the RTR complex
      is involved in DNA repair and in the suppression of homologous recombination (HR)
      in somatic cells. Surprisingly, Arabidopsis thaliana mutants of topoisomerase
      3alpha and RMI1 are also sterile due to extensive chromosome breakage in meiosis
      I, indicating that both proteins are essential for meiotic recombination in
      plants. AtRMI1 harbours an N-terminal DUF1767 domain and two oligosaccharide
      binding (OB)-fold domains. To define specific roles for these individual domains,
      we performed complementation experiments on Atrmi1 mutants with an AtRMI1 full
      length open reading frame (ORF) or deletion constructs lacking specific domains.
      We show that the DUF1767 domain and the OB-fold domain 1 are both essential for
      the function of AtRMI1 in DNA cross-link repair as well as meiotic recombination,
      but partially dispensable for somatic HR suppression. The OB-fold domain 2 is not
      necessary for either somatic or meiotic HR, but it seems to have a minor function
      in DNA cross-link repair. 

PMID- 23956220
TI  - Receptor-mediated delivery of engineered nucleases for genome modification.
AB  - Engineered nucleases, which incise the genome at predetermined sites, have a
      number of laboratory and clinical applications. There is, however, a need for
      better methods for controlled intracellular delivery of nucleases. Here, we
      demonstrate a method for ligand-mediated delivery of zinc finger nucleases (ZFN)
      proteins using transferrin receptor-mediated endocytosis. Uptake is rapid and
      efficient in established mammalian cell lines and in primary cells, including
      mouse and human hematopoietic stem-progenitor cell populations. In contrast to
      cDNA expression, ZFN protein levels decline rapidly following internalization,
      affording better temporal control of nuclease activity. We show that transferrin
      mediated ZFN uptake leads to site-specific in situ cleavage of the target locus.
      Additionally, despite the much shorter duration of ZFN activity, the efficiency
      of gene correction approaches that seen with cDNA-mediated expression. The
      approach is flexible and general, with the potential for extension to other
      targeting ligands and nuclease architectures. 

PMID- 23956221
TI  - Increasing the complexity of chromatin: functionally distinct roles for
      replication-dependent histone H2A isoforms in cell proliferation and
      carcinogenesis.
AB  - Replication-dependent histones are encoded by multigene families found in several
      large clusters in the human genome and are thought to be functionally redundant.
      However, the abundance of specific replication-dependent isoforms of histone H2A
      is altered in patients with chronic lymphocytic leukemia. Similar changes in the
      abundance of H2A isoforms are also associated with the proliferation and
      tumorigenicity of bladder cancer cells. To determine whether these H2A isoforms
      can perform distinct functions, expression of several H2A isoforms was reduced by
      siRNA knockdown. Reduced expression of the HIST1H2AC locus leads to increased
      rates of cell proliferation and tumorigenicity. We also observe that regulation
      of replication-dependent histone H2A expression can occur on a gene-specific
      level. Specific replication-dependent histone H2A genes are either up- or
      downregulated in chronic lymphocytic leukemia tumor tissue samples. In addition,
      discreet elements are identified in the 5' untranslated region of the HIST1H2AC
      locus that confer translational repression. Taken together, these results
      indicate that replication-dependent histone isoforms can possess distinct
      cellular functions and that regulation of these isoforms may play a role in
      carcinogenesis. 

PMID- 23956222
TI  - Euler buckling and nonlinear kinking of double-stranded DNA.
AB  - The bending stiffness of double-stranded DNA (dsDNA) at high curvatures is
      fundamental to its biological activity, yet this regime has been difficult to
      probe experimentally, and literature results have not been consistent. We created
      a 'molecular vise' in which base-pairing interactions generated a compressive
      force on sub-persistence length segments of dsDNA. Short dsDNA strands (<41 base
      pairs) resisted this force and remained straight; longer strands became bent, a
      phenomenon called 'Euler buckling'. We monitored the buckling transition via
      Forster Resonance Energy Transfer (FRET) between appended fluorophores. For low
      to-moderate concentrations of monovalent salt (up to ~150 mM), our results are in
      quantitative agreement with the worm-like chain (WLC) model of DNA elasticity,
      without the need to invoke any 'kinked' states. Greater concentrations of
      monovalent salts or 1 mM Mg(2+) induced an apparent softening of the dsDNA, which
      was best accounted for by a kink in the region of highest curvature. We tested
      the effects of all single-nucleotide mismatches on the DNA bending. Remarkably,
      the propensity to kink correlated with the thermodynamic destabilization of the
      mismatched DNA relative the perfectly complementary strand, suggesting that the
      kinked state is locally melted. The molecular vise is exquisitely sensitive to
      the sequence-dependent linear and nonlinear elastic properties of dsDNA. 

PMID- 23956224
TI  - The prognostic effect of high diagnostic WT1 gene expression in pediatric AML
      depends on WT1 SNP rs16754 status: report from the Children's Oncology Group.
AB  - BACKGROUND: WT1 is aberrantly over-expressed in most cases of AML. We recently
      demonstrated that WT1 SNP rs16754 correlates with favorable outcome and high
      diagnostic WT1 expression in childhood AML. We examined the clinical correlates
      of diagnostic WT1 expression within a contemporary COG trial and determined
      whether its prognostic impact differs between SNP+ and SNP- patients. PROCEDURE:
      WT1 mRNA expression was measured via qRT-PCR in diagnostic specimens obtained
      from 225 patients enrolled on COG-AAML03P1. Direct sequencing of WT1 exon 7 was
      performed to determine SNP rs16754 genotype. WT1 expression was correlated with
      disease characteristics, SNP status, and outcome. RESULTS: Patients were
      categorized into four groups (quartiles: Q1 through Q4) based on diagnostic WT1
      expression for analysis. FLT3/ITD (P = 0.017) and WT1 mutations (P < 0.001) both
      occurred more frequently in patients with the highest WT1 expression. SNP rs16754
      frequency did not vary significantly among the quartiles. When all patients were
      considered, survival outcomes were similar between quartiles. However, when only
      SNP- patients (n = 150) were analyzed, those with highest WT1 expression (Q4) had
      the poorest OS (51% vs. 72% for Q1-Q3, P = 0.006) and EFS (35% vs. 54% for Q1-Q3,
      P = 0.031). Among SNP+ patients (n = 75), survival did not vary significantly
      between WT1 expression quartiles. CONCLUSION: Although WT1 expression was not
      prognostic when all patients were considered together, stratifying patients by
      SNP rs16754 genotype revealed significant differences in outcome. In SNP-
      patients, high WT1 expression predicted decreased survival in univariate, but not
      multivariate, analysis, due to a preponderance of high-risk cyto/molecular
      abnormalities in the highest expression quartile.

PMID- 23956223
TI  - Identification of the Rps28 binding motif from yeast Edc3 involved in the
      autoregulatory feedback loop controlling RPS28B mRNA decay.
AB  - In the yeast Saccharomyces cerevisiae, the Edc3 protein was previously reported
      to participate in the auto-regulatory feedback loop controlling the level of the
      RPS28B messenger RNA (mRNA). We show here that Edc3 binds directly and tightly to
      the globular core of Rps28 ribosomal protein. This binding occurs through a motif
      that is present exclusively in Edc3 proteins from yeast belonging to the
      Saccharomycetaceae phylum. Functional analyses indicate that the ability of Edc3
      to interact with Rps28 is not required for its general function and for its role
      in the regulation of the YRA1 pre-mRNA decay. In contrast, this interaction
      appears to be exclusively required for the auto-regulatory mechanism controlling
      the RPS28B mRNA decay. These observations suggest a plausible model for the
      evolutionary appearance of a Rps28 binding motif in Edc3. 

PMID- 23956225
TI  - Familial ebstein anomaly, left ventricular hypertrabeculation, and ventricular
      septal defect associated with a MYH7 mutation.
AB  - Ebstein anomaly is a rare congenital heart defect that most often occurs
      sporadically within a kindred. Familial cases, although reported, are uncommon.
      At this time, the genetic etiology of Ebstein anomaly is not fully elucidated.
      Here, we describe clinical and molecular investigations of a rare case of
      familial Ebstein anomaly in association with a likely pathogenic mutation of the
      MYH7 gene. The severity of presentation varies, and Ebstein anomaly can be
      observed in association with such other heart defects as ventricular septal
      defect and left ventricular (LV) hypertrabeculation, as seen in our family of
      study. In our family of study, the 31-year-old father and four of his children
      have been diagnosed with Ebstein anomaly. Genetic testing revealed that the
      father was heterozygous for the Glu1220del variant detected in exon 27 of the
      MYH7 gene. The MYH7 gene encodes the beta-myosin heavy chain and is expressed in
      cardiac muscle. DNA sequencing of three of his affected children confirmed that
      they carried the same variant while the fourth affected child was not available
      for testing. This is the first report of familial Ebstein anomaly associated with
      the Glu1220del mutation of the MYH7 gene. The mutation segregates with disease in
      a family with autosomal dominant transmission of congenital heart defects
      including Ebstein anomaly and other associated cardiovascular defects including
      LV hypertrabeculation and ventricular septal defect.

PMID- 23956226
TI  - Centers of endemism and diversity patterns for typhlocybine leafhoppers
      (Hemiptera: Cicadellidae: Typhlocybinae) in China.
AB  - This study identifies 'centers of endemism' for typhlocybine leafhoppers in
      China, revealing diversity patterns and congruence of patterns between total
      species richness and endemism. Distribution patterns of 774 Typhlocybinae (607
      described and 167 undescribed species) were mapped on a 1.5 degrees  * 1.5
      degrees  latitude/longitude grid. Total species richness, endemic species
      richness and weighted endemism richness were calculated for each grid cell. Grid
      cells within the top 5% highest values of weighted endemism richness were
      considered as 'centers of endemism'. Diversity patterns by latitude and altitude
      were obtained through calculating the gradient richness. A congruence of
      diversity patterns between total species richness and endemism was confirmed
      using correlation analysis. To investigate the bioclimatic factors (19 variables)
      contributing to the congruence between total species richness and endemism, we
      compared the factor's difference between non-endemic and endemic species using
      the Kruskal-Wallis test. Eleven centers of endemism, roughly delineated by
      mountain ranges, were identified in central and southern China, including the
      south Yunnan, Hengduan Mountains, Qinling Mountains, Hainan Island, Taiwan Island
      and six mountain areas located in western Sichuan, northwest Fujian, southeast
      Guizhou, southeast Hunan, central and western Guangdong, and north Zhejiang.
      Total species richness and endemic species richness decreased with increased
      latitude and had a consistent unimodal response to altitude. The proportions of
      endemism decreased with increased latitude and increased with rising altitude.
      Diversity patterns between total species richness and endemism were highly
      consistent, and 'Precipitation of Coldest Period' and 'Temperature of Coldest
      Period' may contribute to the congruence of pattern. Migration ability may play a
      role in the relationship of endemism and species richness; climate, environment
      factors and important geologic isolation events can also play crucial effects on
      relationships under special conditions. 

PMID- 23956227
TI  - Microbial biosurfactants as additives for food industries.
AB  - Microbial biosurfactants with high ability to reduce surface and interfacial
      surface tension and conferring important properties such as emulsification,
      detergency, solubilization, lubrication and phase dispersion have a wide range of
      potential applications in many industries. Significant interest in these
      compounds has been demonstrated by environmental, bioremediation, oil, petroleum,
      food, beverage, cosmetic and pharmaceutical industries attracted by their low
      toxicity, biodegradability and sustainable production technologies. Despite
      having significant potentials associated with emulsion formation, stabilization,
      antiadhesive and antimicrobial activities, significantly less output and
      applications have been reported in food industry. This has been exacerbated by
      uneconomical or uncompetitive costing issues for their production when compared
      to plant or chemical counterparts. In this review, biosurfactants properties,
      present uses and potential future applications as food additives acting as
      thickening, emulsifying, dispersing or stabilising agents in addition to the use
      of sustainable economic processes utilising agro-industrial wastes as alternative
      substrates for their production are discussed.

PMID- 23956228
TI  - Transcript analysis and expression profiling of three heat shock protein 70 genes
      in the ectoparasitoid Habrobracon hebetor (Hymenoptera: Braconidae).
AB  - Heat shock proteins (HSPs) are known as chaperones that help with folding of
      other proteins when cells are under environmental stresses. The upregulation of
      HSPs is essential for cold survival during insect diapause. The ectoparasitoid
      Habrobracon hebetor, a potential biological control agent, can enter reproductive
      diapause when reared at low temperature and short photoperiod. However, the
      expression of HSPs during diapause of H. hebetor has not been studied. In this
      study, we sequenced and characterized the full-length complementary DNAs of three
      Hsp70 genes (HhHsp70I, HhHsp70II and HhHsp70III) from H. hebetor. Their deduced
      amino acid sequences showed more than 80% identities to their counterparts from
      other insect species. However, the multiple sequence alignment among the three
      deduced amino acid sequences of HhHsp70s showed only 46% identities. A
      phylogenetic analysis of the three HhHsp70s and all other known Hsp70 sequences
      from Hymenoptera clustered all the Hsp70s into four groups, and the three
      HhHsp70s were distributed into three different groups. Real-time quantitative
      polymerase chain reaction analysis showed that the expression of the three
      HhHsp70 genes in H. hebetor reared at different conditions was quite different.
      HhHsp70I showed higher relative expression when H. hebetor were reared at 27.5
      degrees C than at two lower temperatures (17.5 degrees C and 20 degrees C)
      regardless of the photoperiod, whereas HhHsp70II showed higher expression when H.
      hebetor were reared at 20 degrees C and 10 : 14 L : D than when reared at 17.5
      degrees C and either 16 : 8 L : D or 10 : 14 L : D. In contrast, HhHSP70III was
      expressed at similar levels regardless of the rearing conditions. These results
      may suggest functional differences among the three HhHsp70 genes in H. hebetor. 

PMID- 23956229
TI  - Application of Cydia pomonella expressed sequence tags: Identification and
      expression of three general odorant binding proteins in codling moth.
AB  - The codling moth, Cydia pomonella, is one of the most important pests of pome
      fruits in the world, yet the molecular genetics and the physiology of this insect
      remain poorly understood. A combined assembly of 8 341 expressed sequence tags
      was generated from Roche 454 GS-FLX sequencing of eight tissue-specific cDNA
      libraries. Putative chemosensory proteins (12) and odorant binding proteins
      (OBPs) (18) were annotated, which included three putative general OBP (GOBP), one
      more than typically reported for other Lepidoptera. To further characterize
      CpomGOBPs, we cloned cDNA copies of their transcripts and determined their
      expression patterns in various tissues. Cloning and sequencing of the 698 nt
      transcript for CpomGOBP1 resulted in the prediction of a 163 amino acid coding
      region, and subsequent RT-PCR indicated that the transcripts were mainly
      expressed in antennae and mouthparts. The 1 289 nt (160 amino acid) CpomGOBP2 and
      the novel 702 nt (169 amino acid) CpomGOBP3 transcripts are mainly expressed in
      antennae, mouthparts, and female abdomen tips. These results indicate that next
      generation sequencing is useful for the identification of novel transcripts of
      interest, and that codling moth expresses a transcript encoding for a new member
      of the GOBP subfamily. 

PMID- 23956230
TI  - The influence of sustained dual-factor presentation on the expansion and
      differentiation of neural progenitors in affinity-binding alginate scaffolds.
AB  - Biomaterials capable of controlling the release of multiple growth factors (GFs)
      could potentially promote the integration of co-transplanted neural progenitor
      cells (NPCs) and stimulate the plasticity and regenerability of the lesioned
      spinal cord. As a first step towards the employment of such a vehicle for cell
      therapy, this study examined the capability of an alginate-sulphate/alginate
      scaffold, able to capture and rigorously control the release of GFs, to promote
      the expansion and lineage differentiation of NPCs in vitro. Epidermal growth
      factor (EGF) and fibroblast growth factor-2 (bFGF) were affinity-bound to
      alginate-sulphate (200 ng/scaffold) and the bioconjugates were mixed with
      partially calcium-crosslinked alginate. NPCs isolated from 18 day-old rat embryo
      brains and seeded into the scaffold during preparation were found to proliferate
      and differentiate within the vehicle. A continuous release of both bFGF and EGF
      was noted for a period of 21 days. The concentrations of released GFs were
      sufficient to promote extensive NPC proliferation at initial cultivation times;
      the number of neurospheres in the scaffold was twice the number found in the 2D
      cultures supplemented with 20 ng/ml each factor every 3 days. Between days 10-14,
      when the GF concentrations had substantially declined, extensive cell migration
      from the neurospheres as well as lineage differentiation were noted in the
      scaffold; immunocytochemical analyses confirmed the presence of neurons,
      astrocytes and oligodendrocytes.The scaffold has a potential to serve as cell
      delivery vehicle, with proven capability to promote cell retention and expansion,
      while enabling NPC lineage differentiation in situ.

PMID- 23956231
TI  - Choosing wisely in adult hospital medicine: five opportunities for improved
      healthcare value.
AB  - BACKGROUND: In an effort to lead physicians in addressing the problem of overuse
      of medical tests and treatments, the American Board of Internal Medicine
      Foundation developed the Choosing Wisely campaign. The Society of Hospital
      Medicine (SHM) joined the initiative to highlight the need to critically appraise
      resource utilization in hospitals. METHODS: The SHM employed a staged methodology
      to develop the adult Choosing Wisely list. This included surveys of the
      organization's leaders and general membership, a review of the literature, and
      Delphi panel voting. RESULTS: The 5 recommendations that were subsequently
      approved by the SHM Board are: (1) Do not place, or leave in place, urinary
      catheters for incontinence or convenience or monitoring of output for non
      critically ill patients (acceptable indications: critical illness, obstruction,
      hospice, perioperatively for <2 days for urologic procedures; use weights instead
      to monitor diuresis). (2) Do not prescribe medications for stress ulcer
      prophylaxis to medical inpatients unless at high risk for gastrointestinal
      complications. (3) Avoid transfusions of red blood cells for arbitrary hemoglobin
      or hematocrit thresholds and in the absence of symptoms or active coronary
      disease, heart failure, or stroke. (4) Do not order continuous telemetry
      monitoring outside of the intensive care unit without using a protocol that
      governs continuation. (5) Do not perform repetitive complete blood count and
      chemistry testing in the face of clinical and lab stability. CONCLUSIONS:
      Hospitalists have many opportunities to impact overutilization of care. The adult
      hospital medicine Choosing Wisely recommendations offer an explicit starting
      point for eliminating waste in the hospital.

PMID- 23956232
TI  - Establishing consistent van der Waals volumes of polyatomic ions from crystal
      structures.
AB  - Based on temperature (T) dependent crystal structure data of seven organic salts,
      a radii-based scheme for the calculation of the van der Waals volume (V(vdw)) is
      analyzed. The obtained volumes (V(vdw,r), r=radius-based) are nearly T
      independent. An ion volume partitioning scheme is proposed by fixing the anion
      volumes of [Cl](-), [Br](-), [I](-), [BF(4)](-), [PF(6)](-), [OTf](-) and
      [NTf(2)](-). The van der Waals volumes (V(vdw,r) (+/-)) of 48 ions are
      established, with low standard deviations (0.2-3.6 A(3), 0.1-4.5 % of V(vdw,r)
      (+/-)). The ion volumes are independent of the counterion and one crystal
      structure already suffices for their derivation. Correlations of the viscosity
      with V(vdw,r) via a Litovitz ansatz and our recently derived Arrhenius-type
      approach prove that these volumes are suitable for the volume-based description
      and prediction of IL properties. The corresponding correlation coefficient for
      the latter is R(2)=0.86 for 40 ILs (354 data points) in the T range of 253-373 K.

PMID- 23956233
TI  - Visual acuity of children treated with chemotherapy for optic pathway gliomas.
AB  - BACKGROUND: Chemotherapy is the most common primary treatment modality for
      pediatric optic pathway gliomas (OPGs). Due to the risk of severe visual
      impairment, visual acuity (VA) has become a clinical parameter of fundamental
      importance for children with OPGs. Despite this reality, most studies omit
      crucial information necessary for analysis of the effect of chemotherapy on VA in
      patients with cerebral gliomas. The principal goal of this study was to determine
      the immediate and long-term visual outcome of children treated first with
      chemotherapy for OPGs. PROCEDURE: Retrospective, non-comparative, case series of
      children with OPGs treated initially with chemotherapy. VA was measured prior to
      chemotherapy, directly following chemotherapy, as well as at last follow-up.
      RESULTS: Seven children (14 eyes) were positive for the neurofibromatosis type-1
      (NF1) mutation and 10 children (20 eyes) were without the NF1 mutation
      (sporadic). Three deaths, all in the sporadic cohort, occurred as a result of
      their OPG. Median follow-up time of survivors was 10.54 +/- 4.36 (SD) years. Both
      NF1 mutation positive and sporadic cohorts had deterioration in VA over time;
      however, deterioration was only statistically significant in the sporadic
      population. The percentage of eyes with vision weaker than 20/200 prior to
      chemotherapy, directly following chemotherapy and at last follow-up grew from 18%
      to 24% to 38%, respectively. CONCLUSIONS: In both NF1 mutant and sporadic OPGs,
      VA deteriorated directly following chemotherapy as well as at long-term follow
      up. Despite chemotherapy, eyes with severe functional impairment gradually
      increased over time.

PMID- 23956234
TI  - ACE2 alterations in kidney disease.
AB  - Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that degrades
      angiotensin (Ang) II to Ang-(1-7). ACE2 is highly expressed within the kidneys,
      it is largely localized in tubular epithelial cells and less prominently in
      glomerular epithelial cells and in the renal vasculature. ACE2 activity has been
      shown to be altered in diabetic kidney disease, hypertensive renal disease and in
      different models of kidney injury. There is often a dissociation between tubular
      and glomerular ACE2 expression, particularly in diabetic kidney disease where
      ACE2 expression is increased at the tubular level but decreased at the glomerular
      level. In this review, we will discuss alterations in circulating and renal ACE2
      recently described in different renal pathologies and disease models as well as
      their possible significance. 

PMID- 23956235
TI  - Image quality assessment of three cone beam CT machines using the SEDENTEXCT CT
      phantom.
AB  - OBJECTIVES: The SEDENTEXCT Project proposed quality assurance (QA) methods and
      introduced a QA image quality phantom. A new prototype was recently introduced
      that may be improved according to previous reports. The purpose of this study is
      to evaluate image quality in various protocols of three cone beam CT (CBCT)
      machines using the proposed QA phantom. METHODS: Using three CBCT machines, nine
      image quality parameters, including image homogeneity (noise), uniformity,
      geometrical distortion, pixel intensity value, contrast resolution, spatial
      resolution [line pair (LP) chart, point spread function (PSF) and modulation
      transfer function (MTF)] and metal artefacts, were evaluated using a QA phantom
      proposed by SEDENTEXCT. Exposure parameters, slice thickness and field of view
      position changed variously, and the number of total protocols was 22. RESULTS:
      Many protocols showed a uniform gray value distribution except in the minimum
      slice thickness image acquired using 3D Accuitomo 80 (Morita, Kyoto, Japan) and
      Veraviewepocs 3Df (Morita). Noise levels differed among the protocols. There was
      no geometric distortion, and the pixel intensity values were correlated with the
      CT value. Low contrast resolution differed among the protocols, but high contrast
      resolution performed well in all. Many protocols showed that the maximum line
      pair was larger than 1 LP mm(-1) but smaller than 3 LP mm(-1). PSF and MTF did
      not correlate well with the pixel size. The measured metal artefact areas varied
      for each device. CONCLUSIONS: We studied the image quality of three CBCT machines
      using the SEDENTEXCT phantom. Image quality varied with exposure protocols and
      machines.

PMID- 23956236
TI  - Assessment of buccal marginal alveolar peri-implant and periodontal defects using
      a cone beam CT system with and without the application of metal artefact
      reduction mode.
AB  - OBJECTIVES: To investigate the accuracy of cone beam CT (CBCT) images obtained
      with and without artefact reduction (AR) in detecting simulated buccal peri
      implant and buccal periodontal defects. METHODS: 42 implants inserted into
      edentulous mandibles, and 38 teeth present in dry mandibles were used. Simulated
      buccal peri-implant defects (n = 22) and buccal periodontal defects (n = 22) were
      prepared. 20 implants and 18 teeth without simulated defects were the control
      group. Images of the mandibles were obtained using a Planmeca ProMax((r)) 3D Max
      CBCT unit (Planmeca Oy, Helsinki, Finland). Image reconstructions were prepared
      without and with low, medium and high AR modes. Images were viewed randomly by
      six observers twice for the presence of defects. Kappa coefficient was
      calculated. F2_LD_F1 design for non-parametric analysis of longitudinal data was
      used. Area under curves (AUCs) were calculated for each observer. Significance
      level was taken as alpha = 0.05. RESULTS: Intraobserver kappa ranged from 0.140
      to 0.792 for peri-implant and from 0.189 to 1.0 for periodontal defects. All
      factors were statistically significant (p < 0.001), except for image mode and
      implant brand. Pairwise interactions were found between periodontal defects and
      peri-implant defects (p < 0.001), observers (p < 0.001), observer and image mode
      (p < 0.001), defect model and observer (p < 0.001) and defect model, image mode
      and observer (p = 0.04). AUC values ranged from 0.39 to 0.52 for peri-implant and
      from 0.45 to 0.71 for periodontal defects. Higher AUC values were found for
      periodontal defects than for peri-implant defects. CONCLUSIONS: Buccal peri
      implant defects were more difficult to detect than buccal periodontal defects. No
      difference was found among CBCT images obtained with and without AR modes.

PMID- 23956237
TI  - Influence of rice black streaked dwarf virus on the ecological fitness of non
      vector planthopper Nilaparvata lugens (Hemiptera: Delphacidae).
AB  - Rice black streak dwarf virus (RBSDV) is transmitted by the small brown
      planthopper (SBPH), Laodelphax striatellus (Fallen). Non-vector rice brown
      planthopper (BPH), Nilaparvata lugens (Stal), shares the same host rice plants
      with SBPH in paddy fields. The changes in nutritional composition of rice plants
      infected by RBSDV and the ecological fitness of BPH feeding on the infected
      plants were studied under both artificial climate chamber and field conditions.
      Contents of 16 detected amino acids and soluble sugar in RBSDV infected rice
      plants were higher than those in the healthy ones. On the diseased plants BPH had
      significantly higher nymphal survival rates, nymphal duration of the males,
      weight of the female adults, as well as egg hatchability compared to BPH being
      fed on healthy plants. However, there was no obvious difference in female nymph
      duration, longevity and fecundity. Defense enzymes (superoxidase dismutase, SOD
      and catalase, CAT) and detoxifying enzymes (carboxylesterase, CAE and glutathione
      S-transferase, GST) in BPH adults fed on diseased plants had markedly higher
      activities. The results indicate rice plants infected by RBSDV improved the
      ecological fitness of the brown planthopper, a serious pest but not a transmitter
      of the RBSDV virus. 

PMID- 23956238
TI  - Improved performance of protein-based recombinant gene therapy vehicles by tuning
      downstream procedures.
AB  - Protein engineering offers a robust platform for the design and production in
      cell factories of a plethora of protein-based drugs, including nonviral gene
      therapy vehicles. We have determined here that a protein nanoparticle, formed by
      highly cationic protein monomers, fails to bind exogenous DNA and to promote
      detectable gene expression in target cells despite recruiting all the needed
      functions. Removal of DNA and RNA with nucleases previous to forming complexes
      with exogenous DNA dramatically enhances the ability of the protein to bind and
      transfer DNA to target cell nuclei. These data point out contaminant nucleic
      acids deriving from the cell factory as a major factor impairing the performance
      of protein-based artificial viruses and stress the need of a nuclease step in the
      downstream of proteins whose function is based on cationic domains.

PMID- 23956239
TI  - Future role of MR elastography in tissue engineering and regenerative medicine.
AB  - Tissue engineering (TE) has been introduced for more than 25 years without a boom
      in clinical trials. More than 70 TE-related start-up companies spent more than
      $600 million/year, with only two FDA-approved tissue-engineered products. Given
      the modest performance in clinically approved organs, TE is a tenaciously
      promising field. The TE community is advocating the application of clinically
      driven methodologies in large animal models enabling clinical translation. This
      challenge is hindered by the scarcity of tissue biopsies and the absence of
      standardized evaluation tools, but can be negated through non-invasive assessment
      of growth and integration, with reduced sample size and low cost. Solving this
      issue will speed the transition to cost-efficient clinical studies. In this paper
      we: (a) introduce magnetic resonance elastography to the tissue-engineering and
      regenerative medicine (TERM) community; (b) review recent MRE applications in
      TERM; and (c) discuss future directions of MRE in TERM. We have used MRE to study
      engineered tissues both in vitro and in vivo, where the mechanical properties of
      mesenchymally derived constructs were progressively monitored before and after
      tissues were implanted in mouse models. This study represents a stepping stone
      toward the applications of MRE in directing clinical trials with low cost and
      likely expediting the translation to more relevantly large animal models and
      clinical trials.

PMID- 23956240
TI  - Reply to "Peripheral blood lymphocyte recovery and overall survival in pediatric
      acute lymphoblastic leukemia".

PMID- 23956242
TI  - Intraguild predation among Scolothrips longicornis (Thysanoptera: Thripidae),
      Neoseiulus californicus and Typhlodromus bagdasarjani (Acari: Phytoseiidae) under
      laboratory conditions.
AB  - This study was carried out on the ability of predatory thrips Scolothrips
      longicornis Priesner to feed on 2 phytoseiid species and vice versa. Also the
      effect of predation of Neoseiulus californicus (McGregor) on Typhlodromus
      bagdasarjani Wainstein and Arutunjan and vice versa was evaluated. The larvae,
      prepupae, and pupae of thrips and the eggs, larvae, and protonymphs of
      phytoseiids were selected as intraguild prey. The intraguild predation (IGP)
      among S. longicornis and 2 phytoseiid species was unidirectional and in favor of
      phytoseiids, i.e., S. longicornis was not able to feed on larval stages of 2
      phytoseiids. However, N. californicus and T. bagdasarjani fed on the 1st instar
      larvae (1.39 and 0.80 per day), 2nd instar larvae (0.87 and 0.55 per day),
      prepupae (0.51 and 0.48 per day), and pupae of thrips (0.51 and 0.49 per day,
      respectively). Both phytoseiids fed on eggs, larvae, and protonymphal stages of
      each other. Females of N. californicus consumed more phytoseiid larvae (2.49 per
      day) than T. bagdasarjani, which consumed 1.08 N. californicus larvae per day.
      When Tetranychus urticae was presented as an extraguild prey, intensity of IGP
      between 2 species of phytoseiids and on larval stages of S. longicornis reduced
      significantly. Therefore, it is concluded that (i) IGP existed among the 3
      examined species and lack of feeding of S. longicornis on 2 phytoseiid species
      can be justified by its feeding type (monophagy), (ii) N. californicus was much
      more prone to IGP than was T. bagdasarjani. 

PMID- 23956241
TI  - Memantine for the prevention of cognitive dysfunction in patients receiving whole
      brain radiotherapy: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: To determine the protective effects of memantine on cognitive
      function in patients receiving whole-brain radiotherapy (WBRT). METHODS: Adult
      patients with brain metastases received WBRT and were randomized to receive
      placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24
      weeks. Serial standardized tests of cognitive function were performed. RESULTS:
      Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and
      study compliance were similar in the 2 arms. There was less decline in delayed
      recall in the memantine arm at 24 weeks (P = .059), but the difference was not
      statistically significant, possibly because there were only 149 analyzable
      patients at 24 weeks, resulting in only 35% statistical power. The memantine arm
      had significantly longer time to cognitive decline (hazard ratio 0.78, 95%
      confidence interval 0.62-0.99, P = .01); the probability of cognitive function
      failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm.
      Superior results were seen in the memantine arm for executive function at 8 (P =
      .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed
      recognition (P = .0149) at 24 weeks. CONCLUSIONS: Memantine was well tolerated
      and had a toxicity profile very similar to placebo. Although there was less
      decline in the primary endpoint of delayed recall at 24 weeks, this lacked
      statistical significance possibly due to significant patient loss. Overall,
      patients treated with memantine had better cognitive function over time;
      specifically, memantine delayed time to cognitive decline and reduced the rate of
      decline in memory, executive function, and processing speed in patients receiving
      WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852.

PMID- 23956243
TI  - A whole-genome analysis of a transgenic rice seed-based edible vaccine against
      cedar pollen allergy.
AB  - Genetic modification (GM) by Agrobacterium-mediated transformation is a robust
      and widely employed method to confer new traits to crops. In this process, a
      transfer DNA is delivered into the host genome, but it is still unclear how the
      host genome is altered by this event at single-base resolution. To decipher
      genomic discrepancy between GM crops and their host, we conducted whole-genome
      sequencing of a transgenic rice line OSCR11. This rice line expresses a seed
      based edible vaccine containing two major pollen allergens, Cry j 1 and Cry j 2,
      against Japanese cedar pollinosis. We revealed that genetic differences between
      OSCR11 and its host a123 were significantly less than those between a123 and its
      precedent cultivar Koshihikari. The pattern of nucleotide base substitution in
      OSCR11, relative to a123, was consistent with somaclonal variation. Mutations in
      OSCR11 probably occurred during the cell culture steps. In addition, strand
      specific mRNA-Seq revealed similar transcriptomes of a123 and OSCR11, supporting
      genomic integrity between them. 

PMID- 23956244
TI  - Molecular characterization of DnaJ 5 homologs in silkworm Bombyx mori and its
      expression during egg diapause.
AB  - A comparison of the cDNA sequences (1 056 bp) of Bombyx mori DnaJ 5 homolog with
      B. mori genome revealed that unlike in other Hsps, it has an intron of 234 bp.
      The DnaJ 5 homolog contains 351 amino acids, of which 70 contain the conserved
      DnaJ domain at the N-terminal end. This homolog of B. mori has all desirable
      functional domains similar to other insects, and the 13 different DnaJ homologs
      identified in B. mori genome were distributed on different chromosomes. The
      expressed sequence tag database analysis of Hsp40 gene expression revealed higher
      expression in wing disc followed by diapause-induced eggs. Microarray analysis
      revealed higher expression of DnaJ 5 homolog at 18th h after oviposition in
      diapause-induced eggs. Further validation of DnaJ 5 expression through qPCR in
      diapause-induced and nondiapause eggs at different time intervals revealed higher
      expression in diapause eggs at 18 and 24 h after oviposition, which coincided
      with the expression of Hsp70 as the Hsp 40 is its co-chaperone. This study thus
      provides an outline of the genome organization of Hsp40 gene, and its role in egg
      diapause induction in B. mori.

PMID- 23956245
TI  - Safety and predictors of aneurysm retreatment for remnant intracranial aneurysm
      after initial endovascular embolization.
AB  - INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) is a rare but devastating
      form of stroke. Endovascular therapy has been criticized for its higher rate of
      recanalization and retreatment. The safety and predictors of retreatment are
      unknown. We report the clinical outcomes, imaging outcomes and predictors for
      aneurysm retreatment after initial endovascular embolization. METHOD: We
      identified patients who underwent endovascular retreatment from July 2005 through
      November 2011. Aneurysm and patient data were collected. Periprocedural
      complications were reported as intraoperative perforation (IOP) or thromboembolic
      event (TEE). Aneurysm and patient characteristics were compared between aneurysms
      requiring retreatment and those not requiring retreatment to evaluate aneurysm
      retreatment predictors. RESULTS: A total of 111/871 (13%) aneurysms underwent
      retreatment. Two (0.2%) were retreated for recurrent acute SAH, 82 (74%)
      aneurysms were located in the anterior circulation, 47 (42%) required stent and 5
      (5%) required balloon assist during retreatment. There were a total of 5 (5%) IOP
      and 6 (5%) TEE from which 2 (2%) and 1 (1%) were symptomatic, respectively.
      Overall symptomatic events rate were 2.7%. Patients were followed up for an
      average of 15+/-14 months. Seven (0.8%) aneurysms required a second retreatment
      without any recurrent SAH. Multivariable analysis revealed an OR for aneurysms
      requiring retreatment of 2.965 for aneurysms presenting as aneurysmal SAH, 1.791
      for aneurysms in the posterior circulation and 1.053 for aneurysms with large
      dome size. CONCLUSIONS: Aneurysm retreatment is a safe option without a
      significant increase in morbidity or mortality. SAH, posterior circulation
      aneurysms and larger aneurysm dome size are predictors of aneurysms requiring
      retreatment.

PMID- 23956246
TI  - Elevated serum level of the vascular endothelial growth factor predicts
      radiographic spinal progression in patients with axial spondyloarthritis.
AB  - OBJECTIVE: To investigate the role of serum vascular endothelial growth factor
      (VEGF) as a predictor of radiographic spinal progression in patients with axial
      spondyloarthritis (axSpA). METHODS: Altogether, 172 patients with definite axSpA
      (95 with ankylosing spondylitis and 77 with non-radiographic axSpA) were included
      in this study. Spinal radiographs obtained at baseline and after 2 years of
      follow-up were scored independently by two trained readers in a concealed and
      randomly selected order according to the modified Stoke Ankylosing Spondylitis
      Spine Score (mSASSS) scoring system and for the presence of syndesmophytes.
      Radiographic spinal progression after 2 years was defined as (1) mSASSS worsening
      by >=2 units, and (2) new syndesmophyte formation or formation of a bridging
      syndesmophyte from two single syndesmophytes. Serum VEGF levels were detected at
      baseline. RESULTS: Mean baseline VEGF values were significantly higher in
      patients with mSASSS worsening by >=2 units after 2 years (n=22) than in those
      without progression (562+/-357 vs 402+/-309 pg/mL, respectively, p=0.027) and in
      patients with syndesmophyte formation (n=18) again as compared with those without
      new bone formation (579+/-386 vs 404+/-307 pg/mL, respectively, p=0.041). VEGF as
      a predictor of radiographic spinal progression performed especially well in
      patients who were already at high risk for such a progression due to the presence
      of syndesmophytes at baseline (n=48). In these patients, a VEGF serum level of
      >600 pg/mL had a sensitivity of 53%, a specificity of 97% and an OR=36.6 (95% CI
      3.9 to 341.5) as a predictor of mSASSS worsening by >=2 units. For syndesmophyte
      formation, elevated VEGF demonstrated a sensitivity of 47%, a specificity of 94%
      and an OR=13.6 (95% CI 2.4 to 78.3). CONCLUSIONS: An elevated serum level of VEGF
      (>600 pg/mL) is highly specific as a predictor of radiographic spinal progression
      in patients with axSpA, especially in patients who are at high risk for further
      progression due to the presence of syndesmophytes.

PMID- 23956247
TI  - Identification of a genetic variant for joint damage progression in autoantibody
      positive rheumatoid arthritis.
AB  - BACKGROUND: Joint destruction is a hallmark of autoantibody-positive rheumatoid
      arthritis (RA), though the severity is highly variable between patients. The
      processes underlying these interindividual differences are incompletely
      understood. METHODS: We performed a genome-wide association study on the
      radiological progression rate in 384 autoantibody-positive patients with RA. In
      stage-II 1557 X-rays of 301 Dutch autoantibody-positive patients with RA were
      studied and in stage-III 861 X-rays of 742 North American autoantibody-positive
      patients with RA. Sperm-Associated Antigen 16 (SPAG16) expression in RA synovium
      and fibroblast-like synoviocytes (FLS) was examined using Real-Time Quantitative
      Polymerase Chain Reaction (RT-qPCR) and immunohistochemistry. FLS secrete
      metalloproteinases that degrade cartilage and bone. SPAG16 genotypes were related
      to matrix metalloproteinase (MMP)-3 and MMP-1 expression by FLS in vitro and MMP
      3 production ex vivo. RESULTS: A cluster of single nucleotide polymorphisms
      (SNPs) at 2q34, located at SPAG16, associated with the radiological progression
      rate; rs7607479 reached genome-wide significance. A protective role of rs7607479
      was replicated in European and North American patients with RA. Per minor allele,
      patients had a 0.78-fold (95% CI 0.67 to 0.91) progression rate over 7 years.
      mRNA and protein expression of SPAG16 in RA synovium and FLS was verified. FLS
      carrying the minor allele secreted less MMP-3 (p=1.60*10(-2)). Furthermore,
      patients with RA carrying the minor allele had lower serum levels of MMP-3
      (p=4.28*10(-2)). In a multivariate analysis on rs7607479 and MMP-3, only MMP-3
      associated with progression (p=2.77*10(-4)), suggesting that the association
      between SPAG16-rs7607479 and joint damage is mediated via an effect on MMP-3
      secretion. CONCLUSIONS: Genetic and functional analyses indicate that SPAG16
      influences MMP-3 regulation and protects against joint destruction in
      autoantibody-positive RA. These findings could enhance risk stratification in
      autoantibody-positive RA.

PMID- 23956248
TI  - Laser speckle contrast analysis: a new method to evaluate peripheral blood
      perfusion in systemic sclerosis patients.
AB  - OBJECTIVE: The aim of this pilot study was to assess peripheral blood perfusion
      (PBP) by a new technique, the laser speckle contrast analysis (LASCA), in
      systemic sclerosis (SSc) patients showing different patterns of nailfold
      microangiopathy. Correlations between LASCA and single laser Doppler flowmetry
      (LDF) analysis were also checked. METHODS: Sixty-one SSc patients and 61 healthy
      subjects were enrolled. PBP was evaluated using LASCA and LDF. Scleroderma
      patterns and microangiopathy evolution score (MES) were assessed by nailfold
      videocapillaroscopy (NVC). RESULTS: As detected by LASCA and LDF, PBP was lower
      in SSc patients than in healthy subjects (p<0.0001), showing SSc patients with
      the 'Early', 'Active' or 'Late' NVC pattern a progressively lower PBP (p=0.04 and
      p=0.002, respectively). There was a negative correlation between PBP and MES
      values (p=0.006 and p=0.002 for LASCA and LDF, respectively). A positive
      correlation was detected between LASCA and LDF values, in all subjects
      (p<0.0001). However, LASCA evaluates larger skin areas, is significantly less
      time consuming, is more accepted by patients and shows lower intra-operator
      variability than LDF. CONCLUSIONS: LASCA detected lower PBP in SSc patients than
      in healthy subjects, and for the first time, LASCA perfusion values were found
      correlated with progression of NVC patterns of microangiopathy.

PMID- 23956249
TI  - Evolution of radiographic damage in ankylosing spondylitis: a 12 year prospective
      follow-up of the OASIS study.
AB  - OBJECTIVES: To describe the evolution of radiographic abnormalities of the spine
      in patients with ankylosing spondylitis (AS). METHODS: Patients with AS were
      followed prospectively with 2 yearly radiographs for 12 years. The modified Stoke
      Ankylosing Spondylitis Spine Score (mSASSS) was scored by two readers (R1 and
      R2). New syndesmophytes at uninvolved vertebral corners were computed.
      Radiographic progression was investigated using generalised estimating equations.
      RESULTS: 809 radiographs (presenting 520 at 2 yearly intervals) from 186 patients
      (70% men, mean age 43 (SD 12) years, mean 20 (SD 12) years since symptom onset
      and 83% HLA-B27 positive) were included. Mean mSASSS at baseline was 11.6 (16.2).
      While the course of progression in individual patients was highly variable, and
      still occurred in patients with decades of symptom duration, mean 2 year
      progression was 2.0 (3.5) mSASSS units. Over the entire follow-up, at least one
      new syndesmophyte was found in 55% (R1) and 63% (R2) of patients (38% (R1) and
      39% (R2) of all intervals). In 24% of patients (39% of intervals), there was no
      progression. A progression >=5 mSASSS units occurred in 22% of patients (or in
      12% of intervals). At the group level, a linear time course model fitted the data
      best, with a constant rate over the entire 12 year interval of 0.98 mSASSS
      units/year. Radiographic progression occurred significantly faster in men, in HLA
      B27 positive patients and in patients with a baseline mSASSS>=10. CONCLUSIONS:
      Long term radiographic progression in AS is highly variable in the individual
      patient, more severe in HLA-B27 positive men and still occurs after decades of
      disease. At the group level, however, progression in AS follows an approximately
      linear course.

PMID- 23956250
TI  - Abatacept in relapsing polychondritis.

PMID- 23956251
TI  - Limited evidence that benzodiazepines are beneficial in the treatment of
      disturbed behaviour.

PMID- 23956252
TI  - Proposed cutoff for identifying adult smokeless tobacco users with urinary total
      4-(methylnitrosamino)-1-(3-pyridyl)-1-butanonol: an aggregated analysis of NHANES
      2007-2010 data.
AB  - INTRODUCTION: NNAL [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanonol] is a valid
      biomarker of tobacco use. However; no study has assessed its use in
      distinguishing current smokeless tobacco (SLT) users from nonusers. Therefore,
      this study used aggregated data from the 2007-2008 and 2009-2010 waves of the
      National Health and Nutrition Examination Survey to determine an optimal
      threshold for identifying SLT users with NNAL. METHODS: Optimal urinary total
      NNAL concentrations for discriminating SLT-only users from nonusers of any
      tobacco were determined using receiver operating characteristic analysis.
      Percentage agreement between self-reported SLT use status and NNAL levels was
      calculated overall and by sociodemographic characteristics. All analyses were
      weighted and performed with Stata, Version 11, and MedCalc for Windows, Version
      9.5.0.0. RESULTS: In total, 264 individuals reported exclusively using SLT (and
      no other combustible tobacco product) within the past 5 days, whereas 14,824 were
      self-reported nonusers of any combustible or smokeless tobacco product. The
      optimal NNAL cutoff point was 34.0 pg/ml, which was associated with a high
      sensitivity (95.2%), specificity (93.4%), and overall correct classification rate
      (93.5%). The area under the curve was 98.3% and the corresponding Youden's Index
      was 88.7%. There was high agreement between the proposed NNAL cutoff point and
      self-reported SLT-only use (95.6%) and self-reported SLT nonuse (93.9%).
      CONCLUSION: The proposed cutoff point of 34.0 pg/ml had high sensitivity and
      specificity and may be used by clinicians and researchers to verify or detect
      recent SLT use. This study also indicated that self-reported SLT use among adults
      is a reliable measure and has high agreement with biochemical assessment.

PMID- 23956254
TI  - Statistical genetics with application to population-based study design: a primer
      for clinicians.
AB  - With the completion of the entire human genome sequence and remarkable advances
      in genotyping technologies, there has been an increased interest in the
      application of genetics and genomics in biomedical research over the last decade.
      Large-scale population-based genetic association studies have now become routine
      and their application to several multifactorial diseases such as cardiovascular
      disorders has led to the identification of a number of novel susceptibility
      genes. However, to be able to interpret results from such studies, clinicians
      need to have a basic understanding of unique concepts and issues related to this
      fast-moving area of research. In this primer, we provide a broad overview of
      design, analysis, and methodological issues with a focus on population-based
      study design. 

PMID- 23956255
TI  - Occupational health purchasing behaviour by SMEs--a new theoretical model.
AB  - BACKGROUND: Factors influencing corporate decisions to purchase occupational
      health (OH) are unknown. AIMS: To assist the marketing of OH services to small-
      and medium-sized enterprises (SMEs) by characterizing purchasing behaviour.
      METHODS: We developed a 2*2 model, based on published studies, to describe OH
      purchasing behaviour by SMEs. We tested the model by analysis of responses to a
      cross-sectional market research survey carried out in November 2007. The
      companies surveyed were SMEs employing 30-250 employees, within the localities of
      five UK National Health Service OH services: West London, Buckinghamshire,
      Cambridge, Portsmouth and York. We chose a sample representative of all SMEs for
      each location. The survey explored knowledge of OH and the perceived importance
      of a variety of services. RESULTS: We obtained responses from 387 companies
      (19%); 81% indicated that they knew about OH and 24% had purchased OH services.
      OH was rated 'very important' by 35%, and 65% rated it as 'quite' or 'very
      important'. Sickness absence and its business impact were monitored by 89%.
      Enterprises claiming OH understanding were significantly more likely to purchase
      OH services (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.6-8.0).
      Companies employing fewer than 90 employees were significantly less likely to
      purchase such services than larger ones (OR 0.17, 95% CI 0.09-0.3). CONCLUSIONS:
      OH knowledge and company size are key determinants of SME purchasing behaviour.
      Our findings support our proposed theoretical model. However, more research could
      explore claimed knowledge of OH with respect to the proposed purchaser types and
      business benefits.

PMID- 23956253
TI  - Familial hypercholesterolaemia is underdiagnosed and undertreated in the general
      population: guidance for clinicians to prevent coronary heart disease: consensus
      statement of the European Atherosclerosis Society.
AB  - AIMS: The first aim was to critically evaluate the extent to which familial
      hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was
      to provide guidance for screening and treatment of FH, in order to prevent
      coronary heart disease (CHD). METHODS AND RESULTS: Of the theoretical estimated
      prevalence of 1/500 for heterozygous FH, <1% are diagnosed in most countries.
      Recently, direct screening in a Northern European general population diagnosed
      approximately 1/200 with heterozygous FH. All reported studies document failure
      to achieve recommended LDL cholesterol targets in a large proportion of
      individuals with FH, and up to 13-fold increased risk of CHD. Based on
      prevalences between 1/500 and 1/200, between 14 and 34 million individuals
      worldwide have FH. We recommend that children, adults, and families should be
      screened for FH if a person or family member presents with FH, a plasma
      cholesterol level in an adult >=8 mmol/L(>=310 mg/dL) or a child >=6 mmol/L(>=230
      mg/dL), premature CHD, tendon xanthomas, or sudden premature cardiac death. In
      FH, low-density lipoprotein cholesterol targets are <3.5 mmol/L(<135 mg/dL) for
      children, <2.5 mmol/L(<100 mg/dL) for adults, and <1.8 mmol/L(<70 mg/dL) for
      adults with known CHD or diabetes. In addition to lifestyle and dietary
      counselling, treatment priorities are (i) in children, statins, ezetimibe, and
      bile acid binding resins, and (ii) in adults, maximal potent statin dose,
      ezetimibe, and bile acid binding resins. Lipoprotein apheresis can be offered in
      homozygotes and in treatment-resistant heterozygotes with CHD. CONCLUSION: Owing
      to severe underdiagnosis and undertreatment of FH, there is an urgent worldwide
      need for diagnostic screening together with early and aggressive treatment of
      this extremely high-risk condition.

PMID- 23956256
TI  - Vancomycin dosing in children: what is the question?
AB  - Vancomycin has been in clinical use for over 60 years, but it is still not clear
      what dose should be given to children. Effective treatment with vancomycin
      requires a serum concentration well above the minimum inhibitory concentration
      (MIC) of the bacteria being treated. This is predicted by the area under the
      concentration curve (AUC) divided by the MIC being >400 (AUC/MIC). Recent
      concerns about increasing MIC in staphylococci have lead to recommendations to
      aim for higher trough vancomycin levels (15-20 mg/L). In current practice, most
      children do not achieve these trough levels. Modelling and pharmacokinetic
      studies in children suggest these trough levels may not be necessary if the MIC
      of the organisms is 1 mg/L or less. Further, large-scale studies are needed to
      determine the most appropriate dosing of vancomycin in children. While awaiting
      these, it is time to consider moving to 15 mg/kg 6 h as a standard starting
      regime for vancomycin. It is also vital to determine the MIC of the organism
      being treated, as this may give some guidance about suitable trough levels to be
      aimed for. There is currently little evidence to guide the use of loading doses
      or continuous vancomycin infusions in children. 

PMID- 23956257
TI  - Quality of life in immune thrombocytopenia following treatment.
AB  - OBJECTIVE: To determine the impact of therapy on the reported health-related
      quality of life (HRQoL) in children with primary immune thrombocytopenia (ITP)
      using the Kids ITP tool (KIT). DESIGN: Secondary data analysis of the
      international and North American KIT validation studies. RESULTS: 217 children
      from 6 countries participated in the two studies. The majority of treatments
      occurred in children with newly diagnosed ITP. There was no statistical
      difference in age, platelet count and bleeding severity at presentation in those
      who physicians chose to treat or observe. Self-reported KIT scores did not differ
      between the two groups. The KIT parent-proxy scores were significantly worse for
      newly diagnosed children receiving treatment, especially following prednisone.
      CONCLUSIONS: Treatment of ITP does not improve, and may worsen, the HRQoL of
      children with ITP as measured using the KIT.

PMID- 23956258
TI  - A child an hour: burden of injury deaths among children under 5 in Pakistan.
AB  - BACKGROUND: Globally, more than 875 000 children under the age of 18 die due to
      injury every year. The rate of child injury death is 3.4 times higher in low
      income and middle-income countries than in high-income countries. OBJECTIVES: To
      study injury mortality burden among children under the age of 5 in Pakistan.
      METHODS: Demographic and Health Survey in Pakistan was conducted from September
      2006 until February 2007. It included 95 000 households, out of which 3232
      households had death of a child under the age of 5 from January 2005 onwards. The
      Child Verbal Autopsy Questionnaire (CVAQ) was administered to these households
      with a response rate of 96%. RESULTS: For age group 0-5 years, injury was the
      sixth leading cause of death and was responsible for 2.5% of all deaths (n=73).
      For age group 1-5 years, injury was found to be the third leading cause of death
      (11%) after diarrhoea (18%) and pneumonia (17%). The overall under fives
      mortality rate due to injury was estimated at 39.5 per 100 000 per year in
      Pakistan. Drowning (22%), road traffic injuries (12%), burns (11%) and falls
      (10%) were the most common types of injury. The mortality rate was twice as high
      in rural areas (32 per 100 000; 95% CI 18 to 45), compared to the urban areas (15
      per 100 000; 95% CI 0.3 to 29). CONCLUSIONS: Injury is the third leading cause of
      deaths among children 1-5 in Pakistan. The burden is twice as high in rural
      areas.

PMID- 23956259
TI  - Genomics of cardiac electrical function.
AB  - Proper generation and conduction of the cardiac electrical impulse is essential
      for the continuous coordinated contraction of the heart. Dysregulation of cardiac
      electrical function may lead to cardiac arrhythmias, which constitute a huge
      medical and social burden. Identifying the genetic factors underlying cardiac
      electrical activity serves the double purpose of allowing the early
      identification of individuals at risk for arrhythmia and discovering new
      potential therapeutic targets for prevention. The aim of this review is to
      provide an overview of the genes and genetic loci linked thus far to cardiac
      electrical function and arrhythmia. These genes and loci have been primarily
      uncovered through studies on the familial rhythm disorders and through genome
      wide association studies on electrocardiographic parameters in large sets of the
      general population. An overview of all genes and loci with their respective
      effect is given. 

PMID- 23956260
TI  - The dilemma of choosing the ideal permutation strategy while estimating
      statistical significance of genome-wide enrichment.
AB  - Integrative analyses of genomic, epigenomic and transcriptomic features for human
      and various model organisms have revealed that many such features are nonrandomly
      distributed in the genome. Significant enrichment (or depletion) of genomic
      features is anticipated to be biologically important. Detection of genomic
      regions having enrichment of certain features and estimation of corresponding
      statistical significance rely on the expected null distribution generated by a
      permutation model. We discuss different genome-wide permutation approaches,
      present examples where the permutation strategy affects the null model and show
      that the confidence in estimating statistical significance of genome-wide
      enrichment might depend on the choice of the permutation approach. In those
      cases, where biologically relevant constraints are unclear, it is preferable to
      examine whether key conclusions are consistent, irrespective of the choice of the
      randomization strategy. 

PMID- 23956261
TI  - Non-smoky glycosyltransferase1 prevents the release of smoky aroma from tomato
      fruit.
AB  - Phenylpropanoid volatiles are responsible for the key tomato fruit (Solanum
      lycopersicum) aroma attribute termed "smoky." Release of these volatiles from
      their glycosylated precursors, rather than their biosynthesis, is the major
      determinant of smoky aroma in cultivated tomato. using a combinatorial omics
      approach, we identified the non-smoky glycosyltransferase1 (NSGT1) gene.
      Expression of NSGT1 is induced during fruit ripening, and the encoded enzyme
      converts the cleavable diglycosides of the smoky-related phenylpropanoid
      volatiles into noncleavable triglycosides, thereby preventing their
      deglycosylation and release from tomato fruit upon tissue disruption. In an
      nsgt1/nsgt1 background, further glycosylation of phenylpropanoid volatile
      diglycosides does not occur, thereby enabling their cleavage and the release of
      corresponding volatiles. Using reverse genetics approaches, the NSGT1-mediated
      glycosylation was shown to be the molecular mechanism underlying the major
      quantitative trait locus for smoky aroma. Sensory trials with transgenic fruits,
      in which the inactive nsgt1 was complemented with the functional NSGT1, showed a
      significant and perceivable reduction in smoky aroma. NSGT1 may be used in a
      precision breeding strategy toward development of tomato fruits with distinct
      flavor phenotypes.

PMID- 23956263
TI  - Primary repair of sternal cleft with a double osteochondroplasty flap.
AB  - Sternal cleft is a rare congenital malformation affecting the anterior part of
      the chest wall. Surgical closure is recommended. It should be done early during
      the neonatal period because of the chest's flexibility. Associated abnormalities
      may have been previously excluded. Different surgical repairs have been
      described, but none has been proved to be superior to the others. We present the
      description of 2 cases managed with an original surgical technique. After
      dissecting the two sternal bars, they were approximated with several intercostal
      sutures under close cardiac and respiratory monitoring. A double perichondrium
      flap technique was then used and resulted in a double perichondrium layer. This
      technique is suitable for most cases and offers satisfying anatomical restoring
      and cosmetic results. 

PMID- 23956262
TI  - A genomic-scale artificial microRNA library as a tool to investigate the
      functionally redundant gene space in Arabidopsis.
AB  - Traditional forward genetic screens are limited in the identification of
      homologous genes with overlapping functions. Here, we report the analyses and
      assembly of genome-wide protein family definitions that comprise the largest
      estimate for the potentially redundant gene space in Arabidopsis thaliana. On
      this basis, a computational design of genome-wide family-specific artificial
      microRNAs (amiRNAs) was performed using high-performance computing resources. The
      amiRNA designs are searchable online (http://phantomdb.ucsd.edu). A
      computationally derived library of 22,000 amiRNAs was synthesized in 10
      sublibraries of 1505 to 4082 amiRNAs, each targeting defined functional protein
      classes. For example, 2964 amiRNAs target annotated DNA and RNA binding protein
      families and 1777 target transporter proteins, and another sublibrary targets
      proteins of unknown function. To evaluate the potential of an amiRNA-based
      screen, we tested 122 amiRNAs targeting transcription factor, protein kinase, and
      protein phosphatase families. Several amiRNA lines showed morphological
      phenotypes, either comparable to known phenotypes of single and double/triple
      mutants or caused by overexpression of microRNAs. Moreover, novel morphological
      and abscisic acid-insensitive seed germination mutants were identified for
      amiRNAs targeting zinc finger homeodomain transcription factors and mitogen
      activated protein kinase kinase kinases, respectively. These resources provide an
      approach for genome-wide genetic screens of the functionally redundant gene space
      in Arabidopsis. 

PMID- 23956264
TI  - Are daily routine chest radiographs necessary after pulmonary surgery in adult
      patients?
AB  - A best evidence topic was constructed according to a structured protocol. The
      question addressed was whether daily routine (DR) chest radiographs (CXRs) are
      necessary after pulmonary surgery in adult patients. Of the 66 papers found using
      a report search, seven presented the best evidence to answer the clinical
      question. Four of these seven studies specifically addressed post-cardiothoracic
      adult patients. Three of these seven studies addressed intensive care unit (ICU)
      patients and included post-cardiothoracic adult patients in well-designed
      studies. Six of these seven studies compared the DR CXRs strategy to the
      clinically indicated, on-demand (OD) CXRs strategy. Another study analysed the
      clinical impact of ceasing to perform the DR, postoperative, post-chest tubes
      removal CXRs. The authors, journal, date and country of publication, study type,
      group studied, relevant outcomes and results of these papers are given. We
      conclude that, on the whole, the seven studies are unanimously in favour of
      forgoing DR CXRs after lung resection and advocate OD CXRs. One study suggested
      that hypoxic patients could benefit from a DR CXRs strategy, while other studies
      failed to identify any subgroup for whom performing DR CXRs was beneficial.
      Indeed, DR CXRs, commonly taken after thoracic surgery, have poor diagnostic and
      therapeutic value. Eliminating them for adult patients having undergone thoracic
      surgery significantly decreases the number of CXRs per patient without increasing
      mortality rates, length of hospital stays (LOSs), readmission rates and adverse
      events. Hence, current evidence shows that DR CXRs could be forgone after lung
      resection because OD CXRs, recommended by clinical monitoring, have a better
      impact on management and have not been proved to negatively affect patient
      outcomes. Moreover, an OD CXRs strategy lowers the cost of care. Nevertheless, an
      OD CXRs strategy requires close clinical monitoring by experienced surgeons and
      dedicated intensivists. However, given the published studies' low level of
      evidence, prospective and randomized trials, specifically after thoracic surgery,
      are necessary in order to confirm these results. 

PMID- 23956265
TI  - Occlusive ascending aorta and arch atheroma treated with deep hypothermic
      circulatory arrest and thromboendarterectomy.
AB  - We describe an uncommon presentation of severely advanced aortic atherosclerosis
      in a 48-year old man with a history of hypertension and heavy smoking. Initial
      presentation with upper limb ischaemia led to the diagnosis of an aortic arch
      atheroma occluding 90% of the aortic lumen, managed with deep hypothermic
      circulatory arrest and aortic thromboendarterectomy. To our knowledge, this is
      the first reported case of atherosclerotic plaque resulting in aortic occlusion
      and requiring emergent operative intervention. 

PMID- 23956266
TI  - Localized mesothelioma tumour arising synchronously with a primary contralateral
      lung cancer.
AB  - Mesothelioma is a malignant growth of mesothelial cells found in the serosal
      membrane of pleural, peritoneal and pericardial surfaces as a result of prolonged
      exposure to asbestos. Malignant pleural mesothelioma (MPM) typically presents
      itself in a diffuse pattern of growth over the pleura of the lung or in more rare
      cases as a localized focus (LMPM). We present the first reported case of a
      synchronous LMPM and non-small adenocarcinoma of the lung treated by sequential
      resections. 

PMID- 23956267
TI  - Early and late outcomes of total repair of tetralogy of Fallot: risk factors for
      late right ventricular dilatation.
AB  - OBJECTIVES: This study was undertaken to assess the early and long-term results
      of total repair of tetralogy of Fallot (TOF) and to identify the risk factors
      associated with late right ventricular (RV) dilatation. METHODS: The medical
      records of 326 patients (male:female = 192:134) who underwent total repair of TOF
      at Pusan National and Dong-A University Hospitals between July 1991 and May 2011
      were retrospectively reviewed. Median age and weight at the time of operation
      were 13.0 months and 8.7 kg, respectively. Right ventricular end-diastolic
      dimensions and left ventricular end-diastolic dimensions were obtained during
      follow-up echocardiography to identify the risk factors associated with late RV
      dilatation. RESULTS: There were one operative death (0.3%) and 8 late deaths
      (2.5%). Of late deaths, two were related to operation-related cardiac problems.
      Overall survival rates at 5, 10, and 15 years were 97.0%, 95.4%, and 95.4%, and
      the corresponding freedom from cardiac death were 98.8%, 98.8%, and 98.8%,
      respectively. Freedom from re-operation and re-intervention were 84.4%, 74.2% and
      74.2%. Six patients underwent pulmonary valve replacement during the follow-up
      period. Transannular patch (P = 0.036) and postoperative ventilator support
      period (P < 0.001) were found to be significant risk factors of late RV
      dilatation in multivariate analysis. CONCLUSIONS: Total correction of TOF can be
      performed with a very low mortality rate. However, the postoperative re-operation
      or re-intervention rates remain relatively high. Late RV dilatation after total
      repair of TOF was found to be associated with transannular patch enlargement and
      a longer postoperative ventilator support period.

PMID- 23956268
TI  - Video-assisted thoracic surgery versus open thoracotomy for non-small-cell lung
      cancer: a propensity score analysis based on a multi-institutional registry.
AB  - OBJECTIVES: Comparative long-term survival and oncological outcomes for patients
      with non-small-cell lung cancer (NSCLC) who undergo video-assisted thoracic
      surgery (VATS) or conventional open lobectomy remain uncertain. We conducted a
      multi-institutional propensity-matched study to stratify potential differences in
      these outcomes. METHODS: We established a multi-institutional registry for 4312
      patients with NSCLC who underwent lobectomy between 2001 and 2008 from eight
      institutions in the People's Republic of China. Age, gender, histological type
      and tumour staging were entered into a non-parsimonious multivariable logistic
      regression model to assess long-term survival outcomes. The predicted probability
      derived from the logistic equation was used as the propensity score for each
      individual. Based on similar propensity scores, we matched 1458 of the 1700
      patients who underwent VATS lobectomy with 1458 of the 2612 patients who
      underwent open lobectomy and compared their long-term survival outcomes. RESULTS:
      The mean age of the 2916 matched patients was 59 (standard deviation = 11) years.
      After propensity-matching, VATS and open lobectomy patients were similar in
      regards to important prognostic variables. Three prognostic factors were
      independently associated with improved survival in the multivariate analysis: age
      < 60 (P < 0.001), female gender (P = 0.013) and pathological staging (P < 0.001).
      Patients who underwent VATS vs open lobectomy had similar long-term survival (P =
      0.07). CONCLUSIONS: The current propensity score analysis suggests that well
      matched patients with NSCLC who underwent standardized VATS lobectomy had similar
      long-term survival outcomes when compared with those who underwent open
      lobectomy.

PMID- 23956269
TI  - Single-stage hybrid coronary revascularization with long-term follow-up.
AB  - OBJECTIVES: Hybrid coronary revascularization, performing a left internal
      thoracic artery (LITA) to left anterior descending (LAD) bypass followed by
      percutaneous coronary intervention (PCI) in a non-LAD coronary artery lesion,
      represents an evolving revascularization strategy. It utilizes the survival
      benefit of the LITA-to-LAD bypass, while providing complete revascularization
      with PCI to a non-critical vessel to decrease procedural morbidity. However,
      quantitative patency results and clinical outcomes remain understudied. The
      objective of this study was to assess clinical follow-up and graft and stent
      patency at 6 months and 5 years in a single-stage hybrid revascularization
      population. METHODS: From 2004 to 2012, a total of 96 patients (64 +/- 12 years;
      70 males and 26 females) consented to robotic-assisted LITA harvesting and a
      small left anterior thoracotomy for off-pump coronary artery bypass anastomosis
      onto the LAD. This was followed immediately by PCI in a non-LAD vessel in the
      same fluoroscopy-equipped hybrid operating room. Patients underwent a yearly
      clinical follow-up and a protocol-directed assessment of graft patency via a
      coronary angiogram at 6 months and cardiac computed tomography (CT) angiography
      with single-photon emission computed tomography myocardial perfusion scintigraphy
      (MPS) at 5 years. RESULTS: Successful single-stage hybrid revascularization
      occurred in 94 of the 96 patients (2 patients required intraoperative conversion
      to conventional coronary bypass). Six-month protocol coronary angiogram follow-up
      has been performed in 85 patients. Fitzgibbon Grade A or B LITA-to-LAD patency at
      6-month follow-up was 94% in those studied. A total of 105 stents were deployed
      (89 drug-eluting stents (DES) and 16 bare metal), and at 6-month follow-up in 85
      patients, 79 stents were widely patent; 8 had in-stent restenosis, and 2 were
      completely occluded. To date, 19 patients have undergone 5-year coronary CT
      angiography and MPS. The LITA-to-LAD anastomosis was patent in 17 of the 19
      patients. Of the 19 lesions in which PCI was performed, 17 were widely patent,
      while 2 circumflex DES were occluded. Five-year clinical outcome demonstrated 91%
      survival, 94% freedom from angina and 87% freedom from any form of coronary
      revascularization. CONCLUSIONS: A single-stage hybrid revascularization strategy
      appears to have acceptable 6-month and angiographic patency results for both LITA
      LAD grafts and PCI interventions. Survival, freedom from angina and freedom from
      revascularization also appear favourable at the 5-year clinical follow-up.

PMID- 23956270
TI  - Arterial grafts do not counteract target vessel occlusion.
AB  - OBJECTIVES: Grafted, non-occluded coronary arteries might contribute
      substantially to the myocardial blood supply and serve as a basis for vascular
      collateralization which preserves the myocardium in the event of graft occlusion.
      Early studies indicated that grafting with saphenous vein, but not internal
      mammary arteries, accelerates coronary atherosclerosis. This has not been
      extensively studied for the radial artery, which like the internal mammary artery
      (IMA) is largely resistant to atherosclerosis. A differential effect of various
      grafts might facilitate identification of disease-modifying principles. Our
      surgical cohort represented an opportunity to analyse new native coronary
      occlusions by comparison with preoperative angiograms. METHODS: One hundred and
      two patients underwent angiography 1.3-3.9 years after coronary artery bypass
      surgery, primarily in order to compare the patency of radial artery, IMA and
      saphenous vein grafts. RESULTS: Out of 290 stenotic, grafted vessels, 67 (23%)
      occluded during follow-up. Native occlusion occurred in 47% of the patients and
      correlated with serum-cholesterol. In a per target analysis, independent
      predictors of postoperative native occlusion were the right coronary artery
      territory, patent corresponding graft, the corresponding graft being an IMA and
      end-to-side anastomosis. CONCLUSIONS: Target vessel occlusion is similar with
      radial artery and saphenous vein grafts and proceeds rapidly even in the current
      era of secondary prophylaxis against atherosclerosis. Competitive graft flow
      appears to promote occlusion. Contrary to previous studies, we do not find vein
      grafts to be inferior to IMA grafts with respect to preservation of native vessel
      patency.

PMID- 23956271
TI  - Neuropilin-1 expression in squamous cell carcinoma of the oesophagus.
AB  - OBJECTIVES: The development of new therapeutic targets is needed to change the
      current low survival rates of cancer of the oesophagus. In some clinical trials,
      angiogenic inhibitors, including those targeting the vascular endothelial growth
      factor (VEGF) and its receptors, have proven efficacious. In concert with this,
      neuropilin-1 (NRP1), a coreceptor for VEGF, is expressed by many tumours and may
      be related to their progression. This study aimed to assess the expression and
      prognostic value of fNRP1 in primary squamous cell carcinoma (SCC) of the
      oesophagus. METHODS: The expression of NRP1 receptors was assessed in 60 samples
      of resected oesophageal SCC and adjacent normal mucosa by western blotting,
      immunostaining and real-time quantitative PCR (qPCR). Furthermore, the
      relationship between NRP1 and the clinicopathological parameters was
      investigated. RESULTS: NRP1 staining was limited within normal tissues of the
      oesophagus, while it was prominent in tumour cells and vasculature.
      Overexpression of NRP1 receptors (3.6 +/- 0.48-folds) was apparent in 81.7%
      specimens (n = 60, P = 0.0001). qPCR consistently revealed parallel NRP1-mRNA
      overexpression (3.7 +/- 3.7-folds) (n = 16, P = 0.02). A higher molecular weight
      modified NRP1 (mNRP1) species was identified in a large proportion of the tumour
      specimens (85%), accounting for 71.51 +/- 20.6% of their total NRP1.
      Overexpression of tumour NRP1 was positively correlated with deeper invasion into
      the oesophageal wall (P = 0.05) though mNRP1-positive tumour populations were
      significantly associated with less lymph node metastasis (P = 0.036) and better
      prognostic tumour-node-metastasis stage (P = 0.037) than mNRP1 negative tumours.
      CONCLUSIONS: NRP1 overexpression in oesophageal SCC may contribute to local
      tumour invasiveness but the presence of the mNRP1 subtype correlates with less
      lymph node metastasis and better prognostic stage, suggesting that the balance
      between modified and unmodified NRP1 might be important for determining invasion
      potential.

PMID- 23956272
TI  - Post-traumatic interventricular communication as a life-threatening late
      complication of a penetrating chest injury.

PMID- 23956274
TI  - Guideline for the surgical treatment of atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and its
      prevalence is ~1-2% of the general population, but higher with increasing age and
      in patients with concomitant heart disease. The Cox-maze III procedure was a
      groundbreaking development and remains the surgical intervention with the highest
      cure rate, but due to its technical difficulty alternative techniques have been
      developed to create the lesions sets. The field is fast moving and there are now
      multiple energy sources, multiple potential lesion sets and even multiple
      guidelines addressing the issues surrounding the surgical treatment of AF both
      for patients undergoing this concomitantly with other cardiac surgical procedures
      and also as stand-alone procedures either via sternotomy or via
      videothoracoscopic techniques. The aim of this document is to bring together all
      major guidelines in this area into one resource for clinicians interested in
      surgery for AF. Where we felt that guidance was lacking, we also reviewed the
      evidence and provided summaries in those areas. We conclude that AF surgery is an
      effective intervention for patients with all types of AF undergoing concomitant
      cardiac surgery to reduce the incidence of AF, as demonstrated in multiple
      randomized studies. There is some evidence that this translates into reduced
      stroke risk, reduced heart failure risk and longer survival. In addition,
      symptomatic patients with AF may be considered for surgery after failed catheter
      intervention or even as an alternative to catheter intervention where either
      catheter ablation is contraindicated or by patient choice. 

PMID- 23956276
TI  - Defra takes 'tough and decisive action' at the frontier of bovine TB.

PMID- 23956275
TI  - Broken and scattered sternal wires.

PMID- 23956277
TI  - New wing for referral centre.

PMID- 23956278
TI  - RVC recognised for its commitment to the environment.

PMID- 23956279
TI  - Pilot project to test the best ways of preventing liver fluke.

PMID- 23956281
TI  - FAWC considers the welfare of farmed and park deer.

PMID- 23956282
TI  - Role of the Official Veterinarian in state veterinary medicine.

PMID- 23956283
TI  - An 'exciting and innovative' year for the RCVS.

PMID- 23956287
TI  - Successful candidates welcomed to the Register.

PMID- 23956288
TI  - Encouraging vets to report surgery on pedigree dogs.

PMID- 23956289
TI  - Wildlife hosts for Mycobacterium bovis.

PMID- 23956290
TI  - Bovine TB strategy and new policies for the 'edge area'.

PMID- 23956291
TI  - RCVS fellowship proposals.

PMID- 23956292
TI  - RCVS fellowship proposals.

PMID- 23956293
TI  - Feral pigeon control and welfare.

PMID- 23956294
TI  - Prevalent, treatable and significant: barriers to the control of Trichomonas
      vaginalis in women.

PMID- 23956295
TI  - Basic biology of Trichomonas vaginalis: current explorations and future
      directions.

PMID- 23956298
TI  - Autocrine/paracrine regulatory mechanisms in adrenocortical neoplasms responsible
      for primary adrenal hypercorticism.
AB  - A wide variety of autocrine/paracrine bioactive signals are able to modulate
      corticosteroid secretion in the human adrenal gland. These regulatory factors,
      released in the vicinity of adrenocortical cells by diverse cell types comprising
      chromaffin cells, nerve terminals, cells of the immune system, endothelial cells,
      and adipocytes, include neuropeptides, biogenic amines, and cytokines. A growing
      body of evidence now suggests that paracrine mechanisms may also play an
      important role in the physiopathology of adrenocortical hyperplasias and tumors
      responsible for primary adrenal steroid excess. These intra-adrenal regulatory
      systems, although globally involving the same actors as those observed in the
      normal gland, display alterations at different levels, which reinforce the
      capacity of paracrine factors to stimulate the activity of adrenocortical cells.
      The main modifications in the adrenal local control systems reported by now
      include hyperplasia of cells producing the paracrine factors and abnormal
      expression of the latter and their receptors. Because steroid-secreting adrenal
      neoplasms are independent of the classical endocrine regulatory factors
      angiotensin II and ACTH, which are respectively suppressed by hyperaldosteronism
      and hypercortisolism, these lesions have long been considered as autonomous
      tissues. However, the presence of stimulatory substances within the neoplastic
      tissues suggests that steroid hypersecretion is driven by autocrine/paracrine
      loops that should be regarded as promising targets for pharmacological treatments
      of primary adrenal disorders. This new potential therapeutic approach may
      constitute an alternative to surgical removal of the lesions that is classically
      recommended in order to cure steroid excess. 

PMID- 23956299
TI  - Surgery for 'asymptomatic' mild primary hyperparathyroidism improves some
      clinical symptoms postoperatively.
AB  - OBJECTIVE AND BACKGROUND: Most primary hyperparathyroidism (pHPT) patients do not
      conform to the guidelines for parathyroidectomy established by an international
      panel of specialists and have a mild pHPT. This group is typically defined as
      'asymptomatic'. The primary aim of this study was to determine symptom
      improvement in this 'asymptomatic' group after parathyroidectomy. Secondly, we
      aimed to create a preoperative clinical score predicting postoperative symptom
      resolution. DESIGN: A prospective nonrandomized study included patients with mild
      pHPT. METHODS: A questionnaire (22 items) was given to 'asymptomatic' patients
      preoperatively and at 3, 6, and 12 postoperative months. A logistic regression
      was performed to create a preoperative clinical score. RESULTS: One hundred and
      sixteen patients were included. Postoperatively, HPT was resolved in 98% of
      patients. Twelve of 22 nonspecific symptoms were improved at 1 year. Subgroups
      analysis showed a greater improvement in patients <70 years and those with a
      serum calcium level >=2.6 mmol/l preoperatively. A clinical score, based on age
      and five symptoms, was established to predict the clinical improvement after
      surgery in mild pHPT patients with a positive predictive value of 81%.
      CONCLUSION: Patients with asymptomatic pHPT have clinical improvement of their
      symptoms postoperatively even after 1 year. Younger patients and those with
      higher preoperative calcium levels show the best improvement.

PMID- 23956300
TI  - A novel spliced gene in alcelaphine herpesvirus 1 encodes a glycoprotein which is
      secreted in vitro.
AB  - Herpesviruses often contain cryptic, spliced genes that are not obvious from the
      initial in silico annotation. Alcelaphine herpesvirus 1 (AlHV-1) contains 72
      annotated ORFs but there are also a number of gaps between these that may have
      protein-coding potential. Comparative analysis of coding potential between AlHV-1
      and the related ovine herpesvirus 2 (OvHV-2) revealed a putative novel spliced
      gene that we have termed A9.5. Analysis of cDNA clones from AlHV-1-infected cells
      revealed three overlapping clones corresponding to A9.5 and the coding sequence
      was confirmed by reverse transcription PCR of RNA from AlHV-1-infected cattle
      tissues. The A9.5 gene was predicted to encode a secreted glycoprotein with
      molecular mass 19 kDa. Empirical analysis showed that a recombinant
      haemagglutinin-tagged A9.5 fusion protein was secreted from transfected cells and
      had a molecular mass of 45 kDa, which was reduced to 20 kDa by endoglycosidase F
      treatment, confirming that A9.5 was a secreted glycoprotein. In situ RNA
      hybridization showed that A9.5 was expressed in cells associated with malignant
      catarrhal fever (MCF) lesions in infected cattle. Detailed analysis of the
      available OvHV-2 sequences revealed an homologous gene (Ov9.5) with conserved
      splicing signals and predicted amino acid sequence features in both sequenced
      isolates of this related virus. We have therefore identified a novel spliced gene
      in two related macaviruses that is expressed in MCF lesions. Future work will
      determine its importance for the pathogenesis of disease.

PMID- 23956301
TI  - Human papillomavirus 16-encoded E7 protein inhibits IFN-gamma-mediated MHC class
      I antigen presentation and CTL-induced lysis by blocking IRF-1 expression in
      mouse keratinocytes.
AB  - Human papillomavirus 16 (HPV16) infection causes 50 % or more of cervical cancers
      in women. The HPV16 E7 oncogene is continuously expressed in infected epithelium
      with its oncogenicity linked to cervical cancer. The E7 protein is an ideal
      target in control of HPV infection through T-cell-mediated immunity. Using HPV16
      E7-transgenic mouse keratinocytes (KCs-E7) to investigate T-cell-mediated immune
      responses, we have shown previously that HPV16-encoded E7 protein inhibits IFN
      gamma-mediated enhancement of MHC class I antigen processing and T-cell-induced
      target cell lysis. In this study, we found that HPV16 E7 suppresses IFN-gamma
      induced phosphorylation of STAT1((Tyr701)), leading to the blockade of interferon
      regulatory factor-1 (IRF-1) and transporter associated antigen processing subunit
      1 (TAP-1) expression in KCs-E7. The results of a (51)Cr release assay
      demonstrated that IFN-gamma-treated KCs-E7 escaped from CTL recognition because
      HPV16 E7 downregulated MHC class I antigen presentation on KCs. Restoration of
      IRF-1 expression in KCs-E7 overcame the inhibitory effect of E7 protein on IFN
      gamma-mediated CTL lysis and MHC class I antigen presentation on KCs. Our results
      suggest that HPV16 E7 interferes with the IFN-gamma-mediated JAK1/JAK2/STAT1/IRF
      1 signal transduction pathway and reduces the efficiency of peptide loading and
      MHC class I antigen presentation on KCs-E7. These results may reveal a new
      mechanism whereby HPV16 escapes from immune surveillance in vivo.

PMID- 23956303
TI  - SPOCS: software for predicting and visualizing orthology/paralogy relationships
      among genomes.
AB  - SUMMARY: At the rate that prokaryotic genomes can now be generated, comparative
      genomics studies require a flexible method for quickly and accurately predicting
      orthologs among the rapidly changing set of genomes available. SPOCS implements a
      graph-based ortholog prediction method to generate a simple tab-delimited table
      of orthologs and in addition, html files that provide a visualization of the
      predicted ortholog/paralog relationships to which gene/protein expression
      metadata may be overlaid. AVAILABILITY AND IMPLEMENTATION: A SPOCS web
      application is freely available at http://cbb.pnnl.gov/portal/tools/spocs.html.
      Source code for Linux systems is also freely available under an open source
      license at http://cbb.pnnl.gov/portal/software/spocs.html; the Boost C++
      libraries and BLAST are required.

PMID- 23956304
TI  - Oncofuse: a computational framework for the prediction of the oncogenic potential
      of gene fusions.
AB  - MOTIVATION: Gene fusions resulting from chromosomal aberrations are an important
      cause of cancer. The complexity of genomic changes in certain cancer types has
      hampered the identification of gene fusions by molecular cytogenetic methods,
      especially in carcinomas. This is changing with the advent of next-generation
      sequencing, which is detecting a substantial number of new fusion transcripts in
      individual cancer genomes. However, this poses the challenge of identifying those
      fusions with greater oncogenic potential amid a background of 'passenger' fusion
      sequences. RESULTS: In the present work, we have used some recently identified
      genomic hallmarks of oncogenic fusion genes to develop a pipeline for the
      classification of fusion sequences, namely, Oncofuse. The pipeline predicts the
      oncogenic potential of novel fusion genes, calculating the probability that a
      fusion sequence behaves as 'driver' of the oncogenic process based on features
      present in known oncogenic fusions. Cross-validation and extensive validation
      tests on independent datasets suggest a robust behavior with good precision and
      recall rates. We believe that Oncofuse could become a useful tool to guide
      experimental validation studies of novel fusion sequences found during next
      generation sequencing analysis of cancer transcriptomes. AVAILABILITY AND
      IMPLEMENTATION: Oncofuse is a naive Bayes Network Classifier trained and tested
      using Weka machine learning package. The pipeline is executed by running a
      Java/Groovy script, available for download at www.unav.es/genetica/oncofuse.html.

PMID- 23956302
TI  - Imputation of coding variants in African Americans: better performance using data
      from the exome sequencing project.
AB  - SUMMARY: Although the 1000 Genomes haplotypes are the most commonly used
      reference panel for imputation, medical sequencing projects are generating large
      alternate sets of sequenced samples. Imputation in African Americans using 3384
      haplotypes from the Exome Sequencing Project, compared with 2184 haplotypes from
      1000 Genomes Project, increased effective sample size by 8.3-11.4% for coding
      variants with minor allele frequency <1%. No loss of imputation quality was
      observed using a panel built from phenotypic extremes. We recommend using
      haplotypes from Exome Sequencing Project alone or concatenation of the two panels
      over quality score-based post-imputation selection or IMPUTE2's two-panel
      combination. CONTACT: yunli@med.unc.edu. SUPPLEMENTARY INFORMATION: Supplementary
      data are available at Bioinformatics online.

PMID- 23956305
TI  - A Turing test for artificial expression data.
AB  - MOTIVATION: The lack of reliable, comprehensive gold standards complicates the
      development of many bioinformatics tools, particularly for the analysis of
      expression data and biological networks. Simulation approaches can provide
      provisional gold standards, such as regulatory networks, for the assessment of
      network inference methods. However, this just defers the problem, as it is
      difficult to assess how closely simulators emulate the properties of real data.
      RESULTS: In analogy to Turing's test discriminating humans and computers based on
      responses to questions, we systematically compare real and artificial systems
      based on their gene expression output. Different expression data analysis
      techniques such as clustering are applied to both types of datasets. We define
      and extract distributions of properties from the results, for instance,
      distributions of cluster quality measures or transcription factor activity
      patterns. Distributions of properties are represented as histograms to enable the
      comparison of artificial and real datasets. We examine three frequently used
      simulators that generate expression data from parameterized regulatory networks.
      We identify features distinguishing real from artificial datasets that suggest
      how simulators could be adapted to better emulate real datasets and, thus, become
      more suitable for the evaluation of data analysis tools. AVAILABILITY: See
      http://www2.bio.ifi.lmu.de/~kueffner/attfad/ and the supplement for precomputed
      analyses; other compendia can be analyzed via the CRAN package attfad. The full
      datasets can be obtained from
      http://www2.bio.ifi.lmu.de/~kueffner/attfad/data.tar.gz.

PMID- 23956306
TI  - Incorporating prior knowledge into Gene Network Study.
AB  - MOTIVATION: A major goal in genomic research is to identify genes that may
      jointly influence a biological response. From many years of intensive biomedical
      research, a large body of biological knowledge, or pathway information, has
      accumulated in available databases. There is a strong interest in leveraging
      these pathways to improve the statistical power and interpretability in studying
      gene networks associated with complex phenotypes. This prior information is a
      valuable complement to large-scale genomic data such as gene expression data
      generated from microarrays. However, it is a non-trivial task to effectively
      integrate available biological knowledge into gene expression data when
      reconstructing gene networks. RESULTS: In this article, we developed and applied
      a Lasso method from a Bayesian perspective, a method we call prior Lasso
      (pLasso), for the reconstruction of gene networks. In this method, we partition
      edges between genes into two subsets: one subset of edges is present in known
      pathways, whereas the other has no prior information associated. Our method
      assigns different prior distributions to each subset according to a modified
      Bayesian information criterion that incorporates prior knowledge on both the
      network structure and the pathway information. Simulation studies have indicated
      that the method is more effective in recovering the underlying network than a
      traditional Lasso method that does not use the prior information. We applied
      pLasso to microarray gene expression datasets, where we used information from the
      Pathway Commons (PC) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) as
      prior information for the network reconstruction, and successfully identified
      network hub genes associated with clinical outcome in cancer patients.
      AVAILABILITY: The source code is available at
      http://nba.uth.tmc.edu/homepage/liu/pLasso.

PMID- 23956307
TI  - You only notice them if you understand them: Geriatric syndromes.

PMID- 23956308
TI  - Immunosuppressive drugs after solid organ transplantation.
AB  - In recent years solid organ transplantation has been rapidly developed as a
      therapeutic intervention that is life-saving and greatly contributes to a better
      quality of life in organ recipients. The rapid development has been made possible
      because of a drastic expansion in the immunosuppressive repertoire.
      Unfortunately, the side effects of these drugs can be severe, which is one of the
      reasons that life expectancy of transplant patients still significantly falls
      short of that of the general population. In this review manuscript we will
      discuss current and future immunosuppressive strategies that are employed in
      solid organ transplantation. Expanding our understanding of the human immune
      system will hopefully provide us with newer, smarter drugs that promote
      immunotolerance without the side effects observed today. 

PMID- 23956309
TI  - New treatment options for patients with metastatic prostate cancer.
AB  - Prostate cancer is one of the most common cancers in men. When metastasised (40%
      of patients), classic anti-androgen therapy is the first-line treatment. Usually,
      this treatment becomes ineffective when castration-resistant prostate cancer
      (CRPC) develops. Thus far, docetaxel was the only chemotherapeutic option that
      has shown to be able to extend overall survival and improve quality of life in
      these patients. Recently, cabazitaxel and abiraterone have shown significant
      survival benefits for patients progressive on or after docetaxel treatment, as
      did enzalutamide and radium-223. In North America, immune therapy (sipuleucel-T)
      became available for a subgroup of CRPC patients. These new treatment options
      will change the treatment paradigm of patients with metastatic castration
      resistant prostate cancer. A multidisciplinary approach by both medical
      oncologists and urologists seems mandatory.

PMID- 23956310
TI  - Pre-exposure prophylaxis (PrEP) in HIV-uninfected individuals with high-risk
      behaviour.
AB  - The global incidence of human immunodeficiency virus (HIV) infection has
      decreased by 15% over the past years, but is still too high. Despite current
      programs to reduce the incidence of HIV infection, further approaches are needed
      to limit this epidemic. Oral antiretroviral pre-exposure prophylaxis (PrEP) is
      currently one of the most discussed possible prevention methods. This literature
      study demonstrates whether orally antiretroviral chemoprophylaxis in HIV
      uninfected individuals with high-risk behaviour reduces the transmission of HIV.
      We used the PICO method and conducted a search to identify relevant studies.
      Subjects of the study were HIV-uninfected individuals with high-risk behaviour.
      Intervention was oral PrEP with tenofovir disoproxil fumarate (TDF) alone or plus
      emtricitabine (FTC) versus placebo. The primary outcome was the HIV incidence
      among this high-risk group. Secondary outcomes were adherence to PrEP, frequency
      and type of adverse effects. We identified ten studies from which five randomised
      control trials (RCTs) were included after screening. The results from three out
      of five trials showed a reduction, but two trials showed no protection in
      acquiring HIV infection. There were no significant differences in adverse events.
      The adherence was different among different groups and affected the outcome of
      the studies. In conclusion, this prophylaxis might offer protection when used in
      combination with intense monitoring and guidance in uninfected individuals with a
      high risk of HIV acquisition. However, there are still many unresolved questions.
      Drug adherence seems to be a crucial factor in the effectiveness of PrEP.
      Therefore, individual risk behaviour remains an important determinant for success
      in the prevention of HIV transmission. 

PMID- 23956311
TI  - Smelling the diagnosis: a review on the use of scent in diagnosing disease.
AB  - For centuries, our sense of smell has been used as a diagnostic tool in the
      practice of medicine, be it for recognising gas gangrene on the battle field or
      diabetic ketoacidosis in the emergency room. In recent decades, many scent
      detection studies have been performed with human, animal and electronic noses.
      The ability of humans to diagnose disease by smelling has only rarely been the
      subject of quantitative studies. Scent detection by animals, on the other hand,
      has been addressed in several diagnostic studies, which all suggest similar or
      even superior accuracy compared with standard diagnostic methods. Examples
      include, amongst many others, the use of dogs for the detection of lung cancer in
      breath samples, or rats for Mycobacterium tuberculosis detection in sputum.
      Studies using different types of electronic noses in conditions such as pulmonary
      disease and cancer have also shown promising results with high overall
      sensitivity and specificity. However, results of different types of noses are not
      easily generalisable and independent confirmation studies are generally lacking,
      which should be a focus for future research. In conclusion, scent detection by
      animals and electronic noses holds promise for the future and should receive
      higher priority in terms of research effort and funding. 

PMID- 23956312
TI  - Routine duodenal biopsy to screen for coeliac disease is not effective.
AB  - BACKGROUND: Routine duodenal biopsies during upper gastrointestinal endoscopy
      (UGE) have been suggested to be useful in detecting coeliac disease (CD). However
      results from previous studies are not conclusive. The aim of this study is to
      investigate the diagnostic yield and cost-effectiveness of routine duodenal
      biopsy during UGE. METHODS: In this retrospective single-centre study, we studied
      6442 patients undergoing first-time UGE at the Rijnstate Hospital, Arnhem, the
      Netherlands, from January 2009 to December 2010. All UGE reports were analysed
      for indication, duodenal intubation, and endoscopic aspect of duodenal mucosa.
      Endomysium and tissue transglutaminase antibody titre, when present, were scored
      as positive or negative. CD was defined as Marsh 3a or higher. Costs of duodenal
      biopsies and pathology analysis were calculated. Comparisons were done with T
      tests for continuous data and Chi-square tests for categorical data. RESULTS:
      Forty-one patients had newly diagnosed CD; 34 of these 41 patients had definite
      indications for biopsy prior to UGE, e.g. positive serology or symptoms. Thus,
      routine duodenal biopsies identified seven patients as having CD, who otherwise
      would not have been biopsied. The number needed to biopsy was therefore 577,
      spending more than v 30,000 per case. CONCLUSIONS: We do not recommend routine
      duodenal biopsy to screen for coeliac disease because of the high number needed
      to biopsy as well as high costs.

PMID- 23956313
TI  - Disappearance of epilepsy after resection of catecholamine secreting extra
      adrenal paragangliomas: a case report.
AB  - Epileptic seizures have been associated with increased catecholamine levels,
      however, direct proof is lacking. We report a case with catecholamine secreting
      extra-adrenal paragangliomas and a continuous state of epilepsy not responding to
      therapy. The epileptic seizures resolved after resection of the paragangliomas
      and normalization of catecholamine excretion. 

PMID- 23956314
TI  - Intense muscle aches after cleaning a boat on the Amsterdam canals.

PMID- 23956315
TI  - An enlarged heart with hyperdense consolidation.

PMID- 23956316
TI  - A rare cause of spontaneous perirenal haemorrhage in a patient with ANCA
      associated vasculitis.

PMID- 23956317
TI  - Fingertip necrosis and cervical lymphadenopathy.

PMID- 23956318
TI  - An observational cohort study on geriatric patient profile in an emergency
      department in the Netherlands.
AB  - BACKGROUND: Currently, Dutch emergency care systems focus on rapid emergency
      department (ED) patient management with short completion times, which may not
      meet specific geriatric care needs. METHODS: Six-week observational study in
      patients aged >=70 years, attending the ED of VU University Medical Center (VUmc,
      Amsterdam, the Netherlands) during weekday peak presentation times (10 AM - 10
      PM). RESULTS: During six weeks, a total of 183 patients aged >=70 years attended
      the ED, of which 117 (63.9%) presented during weekday peak hours. One hundred
      patients with a median age of 81 (min-max; 70-97 years) were prospectively
      observed. The majority presented with fall-related complaints (30%), multiple
      comorbidities (>=3 in 50.0%) and polymedication (>=5 in 53.7%). Mean ED length of
      stay was 175.8 (range 20-399) minutes (n=98). Of the patients discharged to their
      usual residence prior to the ED visit (n=58), 36.2% returned to our ED within 30
      days; one in five of these patients had initially presented with a fall.
      CONCLUSION: In this study, fall-related injuries were the most frequent
      presenting complaint during weekday peak presentation times in 70-plus patients.
      Of these, one in five discharged from the ED returned within 30 days. Our
      emergency care system may not adequately cover comprehensive ED geriatric
      assessment, or provide sufficient outpatient care after ED home discharge. We
      believe that EPs should be more aware of the complex problems encountered in
      acute geriatric patients and address follow-up care pathways such as geriatric
      outpatient services, more often in frail elderly patients discharged home.

PMID- 23956319
TI  - Gerontology and geriatrics in Dutch medical education.
AB  - BACKGROUND: The world population is ageing and healthcare services require
      trained staff who can address the needs of older patients. In this study we
      determined how current medical education prepares Dutch students of medicine in
      the field of Gerontology and Geriatrics (G&G). METHODS: Using a checklist of the
      essentials of G&G, we assessed Dutch medical education on three levels. On the
      national level we analysed the latest National Blueprint for higher medical
      education (Raamplan artsopleiding 2009). On the faculty level we reviewed medical
      curricula on the basis of interviews with program directors and inspection of
      course materials. On the student level we assessed the topics addressed in the
      questions of the cross-institutional progress test (CIPT). RESULTS: The National
      Bluepr int contains few specific G&G objectives. Obligatory G&G courses in
      medical schools on average amount to 2.2% of the total curriculum measured as
      European Credit Transfer System units (ECTS). Only two out of eight medical
      schools have practical training during the Master phase in the form of a
      clerkship in G&G. In the CIPT, on average 1.5% of questions cover G&G.
      CONCLUSION: Geriatric education in the Netherlands does not seem to be in line
      with current demographic trends. The National Blueprint falls short of providing
      sufficiently detailed objectives for education on the care of older people. The
      geriatric content offered by medical schools is varied and incomplete, and
      students are only marginally tested on their knowledge of G&G in the CIPT.

PMID- 23956320
TI  - Cilioretinal artery and central retinal vein occlusion after sildenafil use.

PMID- 23956321
TI  - Determinants of assault-related violence in the community: potential for public
      health interventions in hospitals.
AB  - BACKGROUND: Data from emergency departments (EDs) in England describe the
      epidemiology of violent assaults. However, the potential of such data to inform
      hospital-based public health interventions remains unknown. OBJECTIVE: To
      identify determinants of assaults using ED data to inform development of
      programmes delivered in acute Trusts for reducing assault-related injuries in the
      community. METHODS: Data were collected from a large North London acute Trust on
      assault-related injuries reporting to A&E over 18 months (July 2010-February
      2012). Information was recorded on patient demographics and assaults (place of
      assault, type of assault, relation to assailant) through questionnaires
      administered by ED reception staff. RESULTS: 1210 assaults were recorded between
      July 2010 and February 2012. 18% of assaults were severe (strangling, stabbings,
      sexual assaults). 75% of assault victims were men, 37% were young adults (20-30
      years) and 15% were teenagers. A higher proportion of victims lived in more
      deprived areas. Apart from public streets (48%), the main location of assaults
      was at home (20%). Female compared with male victims were significantly more
      likely to be both assaulted at home (OR 6.13; 95% CI 4.41 to 8.54) and to be
      assaulted by a known assailant (family member, friend, partner/ex-partner; OR
      8.20, 95% CI 5.85 to 11.48). CONCLUSIONS: The results highlight the notable
      contribution of domestic violence to assaults presenting to hospital ED. Such
      findings can be used to plan interventions such as screening hospital patients
      for domestic violence. ED data have the potential to inform hospital-based
      initiatives to address issues such as assaults in the local population.

PMID- 23956322
TI  - Cardiac arrest: an infrequent radiologic diagnosis.

PMID- 23956326
TI  - Sirtuin 2 (SIRT2) enhances 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      induced nigrostriatal damage via deacetylating forkhead box O3a (Foxo3a) and
      activating Bim protein.

PMID- 23956327
TI  - Post-reconstruction non-local means filtering methods  using CT side information
      for quantitative SPECT.
AB  - Quantitative SPECT techniques are important for many applications including
      internal emitter therapy dosimetry where accurate estimation of total target
      activity and activity distribution within targets are both potentially important
      for dose-response evaluations. We investigated non-local means (NLM) post
      reconstruction filtering for accurate I-131 SPECT estimation of both total target
      activity and the 3D activity distribution. We first investigated activity
      estimation versus number of ordered-subsets expectation-maximization (OSEM)
      iterations. We performed simulations using the XCAT phantom with tumors
      containing a uniform and a non-uniform activity distribution, and measured the
      recovery coefficient (RC) and the root mean squared error (RMSE) to quantify
      total target activity and activity distribution, respectively. We observed that
      using more OSEM iterations is essential for accurate estimation of RC, but may or
      may not improve RMSE. We then investigated various post-reconstruction filtering
      methods to suppress noise at high iteration while preserving image details so
      that both RC and RMSE can be improved. Recently, NLM filtering methods have shown
      promising results for noise reduction. Moreover, NLM methods using high-quality
      side information can improve image quality further. We investigated several NLM
      methods with and without CT side information for I-131 SPECT imaging and compared
      them to conventional Gaussian filtering and to unfiltered methods. We studied
      four different ways of incorporating CT information in the NLM methods: two known
      (NLM CT-B and NLM CT-M) and two newly considered (NLM CT-S and NLM CT-H). We also
      evaluated the robustness of NLM filtering using CT information to erroneous CT.
      NLM CT-S and NLM CT-H yielded comparable RC values to unfiltered images while
      substantially reducing RMSE. NLM CT-S achieved -2.7 to 2.6% increase of RC
      compared to no filtering and NLM CT-H yielded up to 6% decrease in RC while other
      methods yielded lower RCs than them: Gaussian filtering (up to 11.8% decrease in
      RC), NLM method without CT (up to 9.5% decrease in RC), and NLM CT-M and NLM CT-B
      (up to 19.4% decrease in RC). NLM CT-S and NLM CT-H achieved 8.2 to 33.9% and 
      0.9 to 36% decreased RMSE on tumors compared to no filtering respectively while
      other methods yielded less reduced or increased RMSE: Gaussian filtering (up to
      7.9% increase in RMSE), NLM method without CT (up to 18.3% increase in RMSE), and
      NLM CT-M and NLM CT-B (up to 31.5% increase in RMSE). NLM CT-S and NLM CT-H also
      yielded images with tumor shapes that better-matched the true shapes than other
      methods. All NLM methods using CT information were robust to small
      misregistration between SPECT and CT, but NLM CT-S and NLM CT-H were more
      sensitive than NLM CT-M and NLM CT-B to missing CT information.

PMID- 23956328
TI  - Automated segmentation of pulmonary structures in  thoracic computed tomography
      scans: a review.
AB  - Computed tomography (CT) is the modality of choice for imaging the lungs in vivo.
      Sub-millimeter isotropic images of the lungs can be obtained within seconds,
      allowing the detection of small lesions and detailed analysis of disease
      processes. The high resolution of thoracic CT and the high prevalence of lung
      diseases require a high degree of automation in the analysis pipeline. The
      automated segmentation of pulmonary structures in thoracic CT has been an
      important research topic for over a decade now. This systematic review provides
      an overview of current literature. We discuss segmentation methods for the lungs,
      the pulmonary vasculature, the airways, including airway tree construction and
      airway wall segmentation, the fissures, the lobes and the pulmonary segments. For
      each topic, the current state of the art is summarized, and topics for future
      research are identified.

PMID- 23956329
TI  - Antenatal surveillance through estimates of the sources underlying the abdominal
      phonogram: a preliminary study.
AB  - Today, it is generally accepted that current methods for biophysical antenatal
      surveillance do not facilitate a comprehensive and reliable assessment of foetal
      well-being and that continuing research into alternative methods is necessary to
      improve antenatal monitoring procedures. In our research, attention has been paid
      to the abdominal phonogram, a signal that is recorded by positioning an acoustic
      sensor on the maternal womb and contains valuable information about foetal
      status, but which is hidden by maternal and environmental sources. To recover
      such information, previous work has used single-channel independent component
      analysis (SCICA) on the abdominal phonogram and successfully retrieved estimates
      of the foetal phonocardiogram, the maternal phonocardiogram, the maternal
      respirogram and noise. The availability of these estimates made it possible for
      the current study to focus on their evaluation as sources for antenatal
      surveillance purposes. To this end, the foetal heart rate (FHR), the foetal heart
      sounds morphology, the maternal heart rate (MHR) and the maternal breathing rate
      (MBR) were collected from the estimates retrieved from a dataset of 25 abdominal
      phonograms. Next, these parameters were compared with reference values to
      quantify the significance of the physiological information extracted from the
      estimates. As a result, it has been seen that the instantaneous FHR, the
      instantaneous MHR and the MBR collected from the estimates consistently followed
      the trends given by the reference signals, which is a promising outcome for this
      preliminary study. Thus, as far as this study has gone, it can be said that the
      independent traces retrieved by SCICA from the abdominal phonogram are likely to
      become valuable sources of information for well-being surveillance, both foetal
      and maternal. 

PMID- 23956330
TI  - Advancement of the premaxilla with distraction osteogenesis.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of premaxillary
      advancement with distraction osteogenesis (DO) on the skeletal, dental, and soft
      tissues. MATERIALS AND METHODS: A total of 21 cases with Angle class I molar
      relationship and negative overjet or edge-to-edge incisor relationship were
      included. Due to patient relocation during fixed orthodontic treatment the
      results of 19 patients (9 females, 10 males) were reported. Their average
      chronological age was 16.18 +/- 3.10 years. An individual tooth-borne distraction
      appliance was used. Skeletal, dental, and soft tissue changes were evaluated on
      cephalograms obtained before treatment (T1), at the end of the consolidation
      period (T2) and fixed orthodontic treatment (T3). Friedman and Wilcoxon tests
      were applied to determine the significant differences during T1-T2, T2-T3, and T1
      T3 periods. RESULTS: At T2 forward movements of ANS, A, and upper incisors were
      significant. Significant increases of SNA, ANB, and overjet were obtained. The
      soft tissue points of Pn, Sn, Ss, Ls showed significant anterior movement. Arch
      length increase of 10.76 mm was significant. At T3 the decreases of SNA and ANB
      angles, and FH ? N-A distance were significant. Pn point showed significant
      anterior movement. Total treatment time showed significant anterior movement of
      points ANS, A, and upper incisors. Significant increase of SNA and ANB angles was
      noted. The soft tissue points followed the movement of the underlying hard
      tissue. LIMITATION: A class III control group could not be established for
      ethical reasons. CONCLUSIONS: The facial profile was improved and space was
      obtained to solve the maxillary anterior crowding with premaxillary advancement
      through DO.

PMID- 23956331
TI  - Is maxillary dental arch constriction common in Japanese male adult patients with
      obstructive sleep apnoea?
AB  - OBJECTIVES Little is known about the contributions of a narrow maxillary dental
      arch and maxillary skeletal constriction to the development of obstructive sleep
      apnoea (OSA). Therefore, the purpose of this study was to clarify the
      relationships between maxillary dental arch width and OSA and between maxillary
      skeletal constriction and OSA in Japanese male patients.METHODS Study models for
      164 Japanese male OSA patients were fabricated for dental arch analyses. We
      compared the patients' dental arch widths with the standard value for Japanese
      males. Moreover, the associations between the upper dental arch width and the
      apnoea-hypopnoea index (AHI), body mass index, skeletal pattern (SNA, SNB, and
      ANB), cross-sectional area of tongue obtained from an upright lateral
      cephalogram, lower dental arch width, overjet, and overbite were also
      examined.RESULTS Although a narrower upper dental arch was associated with
      severer OSA, the upper dental arch in OSA patients was not significantly narrower
      than the Japanese standard value. However, the results of a multiple regression
      analysis revealed that the upper dental arch became narrower as the mandible was
      positioned more rearward relative to the maxilla.CONCLUSIONS We conclude that
      dental arch constriction in the maxilla could be associated with the development
      of OSA but is not a typical feature of our sample of Japanese OSA patients.
      Moreover, the factor that aggravates OSA is not maxillary skeletal constriction
      but rather maxillary dental arch constriction related to antero-posterior
      skeletal discrepancy.

PMID- 23956332
TI  - How absolute EIT reflects the dependence of unilateral lung aeration on hyper
      gravity and weightlessness?
AB  - We studied the influence of three gravity levels (0, 1 and 1.8 g) on unilateral
      lung aeration in a left lateral position by the application of absolute
      electrical impedance tomography. The electrical resistivity of the lung tissue
      was considered to be a meaningful indicator for lung aeration since changes in
      resistivity have already been validated in other studies to be proportional to
      changes in lung volume. Twenty-two healthy volunteers were studied during
      parabolic flights with three phases of different gravity, each lasting ~20-22 s.
      Spontaneous breathing at normal tidal volume VT and at increased VT was
      performed. During transition to hyper-gravity mean expiratory resistivities (+/
      SD in Omegam) increased at normal VT in the upper (right) lung from 7.6 +/- 1.5
      to 8.0 +/- 1.7 and decreased from 5.8 +/- 1.2 to 5.7 +/- 1.2 in the lower (left)
      lung. Inspiratory resistivity values are 8.3 +/- 1.6 to 8.8 +/- 1.8 (right) and
      6.3 +/- 1.3 to 6.0 +/- 1.3 (left). At increased VT, the changes in resistivities
      at end-expiration were 7.7 +/- 1.5 to 8.0 +/- 1.7 (right) and 5.8 +/- 1.2 to 5.7
      +/- 1.2 (left). Corresponding end-inspiratory values are 9.9 +/- 1.9 to 10.0 +/-
      2.0 (right) and 8.6 +/- 2.1 to 7.9 +/- 2.0 (left). During weightlessness, the
      distortion in the lungs disappeared and both lungs showed a nearly identical
      aeration, which was between the levels displayed at normal gravity. The small
      increase in resistivity for the upper lung during transition to hyper-gravity
      from 1 to 1.8 g at increased VT suggests that the degressive part of the pressure
      volume curve has already been reached at end-inspiration. The results for a left
      lateral position are in agreement with West's lung model which has been
      introduced for cranio-caudal gravity dependence in the lungs. 

PMID- 23956333
TI  - Beat-to-beat QT interval variability and T-wave amplitude in patients with
      myocardial infarction.
AB  - The purpose of this study was to investigate the effects of T-wave amplitude and
      ECG lead on beat-to-beat QT interval variability (QTV) in patients with
      myocardial infarction (MI) compared to healthy subjects. Standard resting 12-lead
      ECGs of 79 MI patients and 69 healthy subjects were investigated. Beat-to-beat QT
      intervals were measured separately for each lead using a template matching
      algorithm. In addition, we extracted the beat-to-beat T-wave amplitude in each
      lead. We computed the standard deviation of beat-to-beat QT intervals as a marker
      of QTV for both healthy subjects and MI patients. Significant QTV differences
      were observed between the 12 ECG leads as well as between the groups of healthy
      subjects and MI patients. Beat-to-beat QTV was significantly higher in MI
      patients than in healthy subjects for half of the leads. Furthermore, significant
      T-wave amplitude differences across leads and between groups were observed. A
      significant inverse relation between beat-to-beat QTV and T-wave amplitude was
      demonstrated. The group differences in QTV remained significant after co-varying
      for the T-wave amplitude. In conclusion, the increase in beat-to-beat QTV that
      has been repeatedly reported in patients with MI is partly due to the lower T
      wave amplitudes. However, QTV remains significantly increased in MI patients
      after covarying for this effect. 

PMID- 23956334
TI  - Incidence and clinical presentation of groin injuries in sub-elite male soccer.
AB  - BACKGROUND: Groin injuries cause major problems in the football codes, as they
      are prevalent and lead to prolonged symptoms and high recurrence. The aim of the
      present study was to describe the occurrence and clinical presentation of groin
      injuries in a large cohort of sub-elite soccer players during a season. METHODS:
      Physiotherapists allocated to each of the participating 44 soccer clubs recorded
      baseline characteristics and groin injuries sustained by a cohort of 998 sub
      elite male soccer players during a full 10-month season. All players with groin
      injuries were examined using the clinical entity approach, which utilises
      standardised reproducible examination techniques to identify the injured
      anatomical structures. The exposure time and the injury time were also recorded.
      Injury time was analysed using multiple regression on the log of the injury times
      as the data were highly skewed. Effects are thus reported at relative injury time
      (RIT). RESULTS: Adductor-related groin injury was the most common entity found
      followed by iliopsoas-related and abdominal-related injuries. The dominant leg
      was significantly more often injured. Age and previous groin injury were
      significant risk factors for sustaining a groin injury. Groin injuries were
      generally located on the same side as previously reported groin injuries.
      Adductor-related injuries with no abdominal pain had significantly longer injury
      times compared to injuries with no adductor and no abdominal pain (RIT 2.28, 95%
      CI 1.22 to 4.25, p=0.0096). Having both adductor and abdominal pain also
      increased the injury time significantly when compared to injuries with no
      adductor and no abdominal pain (RIT=4.56, 95% CI 1.91 to 10.91, p=0.001).
      CONCLUSION: Adductor-related groin injury was the most common clinical
      presentation of groin injuries in male soccer players and the cause of long
      injury time, especially when combined with abdominal-related injury.

PMID- 23956335
TI  - Sports participation of individuals with major upper limb deficiency.
AB  - BACKGROUND: The aim of this study was to analyse sports participation of
      individuals with upper limb deficiency (ULD) and associated factors. METHODS:
      Individuals with ULD originating from the Netherlands were invited, via their
      attending physiatrist or prosthetist, to answer a digital or paper questionnaire.
      The questionnaire consisted of 34 items related to personal characteristics, type
      of deficiency and participation in sports. RESULTS: Of the 175 respondents, 57%
      participated in sports for at least 60 min/week (athletes). Results of logistic
      regression analyses indicated that the presence of an additional health problem
      hindering sports participation (beta=-1.31, p<0.001) and a more proximal onset of
      the limb deficiency (beta=0.76, p=0.022) had a negative influence on sports
      participation. For individuals with an acquired ULD, a medium education level
      (beta=0 0.77, p=0.108) and participation in sports before their amputation
      (beta=1.11, p=0.007) had a positive influence on sports participation. The desire
      to stay healthy and the pleasure derived from sports participation represented
      the main reasons for participation in sports according to athletes. The presence
      of an additional medical problem and a lack of motivation were reasons for non
      athletes to not participate in sports. CONCLUSIONS: The majority of individuals
      with ULD participate in sports regularly. The presence of an additional medical
      problem, as well as the level of ULD, educational level and participation in
      sports before amputation, was related to participation in sports.

PMID- 23956336
TI  - NCAA concussion education in ice hockey: an ineffective mandate.
AB  - BACKGROUND/AIM: Despite concussion education being increasingly mandated by
      states and sports leagues, there has been limited evaluation of what education is
      in fact effective. The National Collegiate Athletic Association (NCAA) currently
      mandates that institutions provide concussion education, without specifying
      content or delivery. The present study evaluated the effectiveness of this
      general mandate, as enacted for male collegiate ice hockey teams within one
      conference of competition. METHODS: In a prospective cohort design, 146 players
      from 6 male collegiate ice hockey teams in one Division 1 conference completed
      written surveys before and after receiving their institution-determined
      concussion education. Knowledge, attitudes, perceived norms and behavioural
      intention were assessed using validated measures. Education content and delivery
      was assessed by open-ended responses and consultation with team athletic
      trainers. RESULTS: All teams received concussion education material; however,
      content and delivery varied. Rates of material recall differed by delivery
      format. Considering all teams together, there were no significant improvements in
      knowledge and only a very small decrease in intention to continue playing while
      experiencing symptoms of a concussion. Pre-education and post-education, there
      were significant between-team differences in attitudes towards concussion
      reporting and behavioural intention. CONCLUSIONS: The NCAA's general education
      mandate was divergently enacted; it did not significantly change the constructs
      of interest nor did it mitigate the pre-education team differences in these
      constructs. Existing educational materials should be evaluated, theory and
      evidence-driven materials developed, and mandates extended to, at a minimum,
      recommend materials found to be effective in changing concussion-reporting
      behaviour.

PMID- 23956337
TI  - Body composition in sport: interobserver reliability of a novel ultrasound
      measure of subcutaneous fat tissue.
AB  - BACKGROUND: Very low body mass, extreme mass changes, and extremely low per cent
      body fat are becoming increasingly common in many sports, but sufficiently
      reliable and accurate field methods for body composition assessment in athletes
      are missing. METHODS: Nineteen female athletes were investigated (mean (SD) age:
      19.5 (+/- 3.3) years; body mass: 59.6 (+/- 7.6) kg; height: 1.674 (+/- 0.056) m;
      BMI: 21.3 (+/- 2.3) kg/m(2)). Three observers applied diagnostic B-mode
      ultrasound (US) combined with the evaluation software for subcutaneous adipose
      tissue measurements at eight ISAK sites (International Society for the
      Advancement of Kinanthrometry). Regression and reliability analyses are
      presented. RESULTS: US measurements and evaluation of subcutaneous adipose tissue
      (SAT) thicknesses (including fibrous structures: D(included); n=378) resulted in
      an SE of estimate SEE=0.60 mm, R(2)=0.98 (p<0.001), limit of agreement LOA=1.18,
      ICC=0.968 (0.957-0.977). Similar values were found for D(excluded): SEE=0.68 mm,
      R(2)=0.97 (p<0.001). D(included) at individual ISAK sites: at biceps, R(2)=0.87
      and intraclass-correlation coefficient ICC=0.811 were lowest and SEE=0.79 mm was
      highest. Values at all other sites ranged from R(2): 0.94-0.99, SEE: 0.42-0.65
      mm, and ICC: 0.917-0.985. Interobserver coefficients ranged from 0.92 to 0.99,
      except for biceps (0.74, 0.83 and 0.87). Evaluations of 20 randomly selected US
      images by three observers (D(included)) resulted in: SEE=0.15 mm,
      R(2)=0.998(p<0.001), ICC=0.997 (0.993, 0999). CONCLUSIONS: Subject to optimal
      choice of sites and certain standardisations, US can offer a highly reliable
      field method for measurement of uncompressed thickness of the SAT. High accuracy
      and high reliability of measurement, as obtained with this US approach, are
      essential for protection of the athlete's health and also for optimising
      performance.

PMID- 23956338
TI  - FYSS (physical activity book for prevention and treatment): behavioural change
      also for the physician?

PMID- 23956339
TI  - Second generation HIV surveillance in Pakistan: evidence for understanding the
      epidemic and planning a response.

PMID- 23956340
TI  - The Quality and Safety Track: Training Future Physician Leaders.
AB  - Future physician leaders will need the knowledge and skills necessary to improve
      systems of care. To address this need, Pritzker School of Medicine implemented a
      4-year scholarly track in quality and patient safety for medical students. The
      Quality and Safety Track (QST) includes an intensive elective that teaches basic
      quality-improvement skills, an individual mentored scholarly project, and
      engagement in the Institute for Healthcare Improvement Open School. The first
      year elective incorporates a group project that allows students to apply basic
      process improvement skills. Institutional quality and safety leaders also present
      their work, giving students context for how these skills are used. To date, 23
      students have completed the elective, and 11 chose to pursue QST throughout their
      medical school experience. Students who completed the elective reported improved
      confidence in using core quality improvement skills. QST is a feasible and
      innovative program to develop future health care leaders in quality and safety. 

PMID- 23956341
TI  - Preventability of 30-day readmissions for heart failure patients before and after
      a quality improvement initiative.
AB  - The objective of this study was to estimate the frequency of heart failure (HF)
      readmissions that can be prevented through a quality improvement (QI) program.
      All HF patients at the University of Connecticut Health Center who had a
      readmission within 30 days of discharge in the year before (2008) and the year
      after (2011) a QI program were studied. Through chart review, the percentage of
      patients who had preventable readmissions in each year was estimated. Prior to
      the QI initiative, chart reviewers identified that 20% to 30% of readmissions
      were preventable. The decrease in readmissions after the QI program was similar
      at 28%. Fewer readmissions after the QI initiative were deemed preventable
      compared with before. In conclusion, this study found a percentage of preventable
      readmissions similar to the actual 28% reduction in readmissions after a QI
      program was launched. Preventable readmissions were less common after the QI
      program was in place. 

PMID- 23956342
TI  - Cognitive remediation as a treatment for major depression: A rationale, review of
      evidence and recommendations for future research.
AB  - OBJECTIVE: There is considerable literature regarding the effectiveness of
      cognitive remediation (CR) in schizophrenia and in conditions such as stroke and
      traumatic brain injury. Patients with major depressive disorder (MDD) present
      with significant cognitive impairment which in many cases may not resolve with
      treatment. Neurobiological data suggest that this may relate to underlying
      dysfunction of pre-frontal cortical areas of the brain and their connections with
      limbic structures. There has been limited research into specific CR to activate
      these areas and target impaired cognitive function in MDD. We therefore review
      current evidence, examine the theoretical basis for and present a rationale for
      research into CR in MDD. In addition, we will examine important methodological
      issues in developing such an approach. METHOD: Based on preliminary studies using
      CR-based techniques, data from CR in schizophrenia, data regarding baseline and
      residual cognitive impairment in depression, and knowledge of the neurobiology of
      MDD, we examine the possible utility of CR strategies in the treatment of MDD and
      make recommendations for research in this area. RESULTS: A small number of
      previous studies have examined specific CR in MDD. The studies are small and
      inconclusive. However, data on the neuropsychological function and neurobiology
      of MDD suggest that this is an approach that deserves further attention and
      research. CONCLUSIONS: Further research is required in carefully selected
      populations, using well-defined CR techniques and some form of comparator
      treatment.

PMID- 23956343
TI  - Deliberate total parathyroidectomy: a potentially novel therapy for tumor-induced
      hypophosphatemic osteomalacia.
AB  - BACKGROUND: Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic
      metabolic bone disorder that can be cured by removing or ablating the offending
      tumor. However, when the tumor cannot be localized, lifelong therapy with oral
      phosphate and calcitriol or cinacalcet with close monitoring is required. CASE
      REPORT: A 56-year-old man was diagnosed with TIO in 1990. Initial therapy
      consisted of oral phosphate and calcitriol with symptomatic and biochemical
      improvement and healing of osteomalacia. Eight years later, hypercalcemic
      hyperparathyroidism developed, requiring subtotal parathyroidectomy with a
      transient increase in serum phosphate and normalization of serum calcium and PTH.
      Recurrent hypercalcemic hyperparathyroidism developed after 10 years of medical
      therapy. A deliberate total parathyroidectomy produced a prompt rise in serum
      phosphate into the normal range > 3.0 mg/dL and remained normal during the next 4
      years of follow-up, despite continued very high serum fibroblast growth factor-23
      levels throughout the 23-year follow-up. CONCLUSION: We report an unusual case of
      a TIO patient with long-term follow-up who developed recurrent hypercalcemic
      hyperparathyroidism on long-term oral phosphate therapy. Deliberate total
      parathyroidectomy normalized serum phosphate despite persistently elevated
      fibroblast growth factor-23 levels. Total parathyroidectomy offers a potentially
      novel therapy in some patients with TIO in whom medical therapy is not feasible
      or the tumor is unresectable.

PMID- 23956344
TI  - First birth achieved after in vitro maturation of oocytes from a woman endowed
      with multiple antral follicles unresponsive to follicle-stimulating hormone.
AB  - CONTEXT: The association of primary amenorrhea, gonadotropin levels at menopausal
      range, and normal antral follicle endowment is a rare clinical condition that
      suggests unresponsiveness of antral follicles to FSH. This affection is
      frequently misdiagnosed ovarian failure and patients are referred to egg donation
      to treat their infertility. Because these patients notably have an age-compatible
      number of antral follicles, we hypothesized that in vitro maturation (IVM) of
      oocytes might constitute a useful approach for treating their infertility.
      OBJECTIVE: We report the first pregnancy and live birth obtained after IVM of
      oocytes in a 29-year-old patient suffering from ovarian resistance to FSH.
      DESIGN: This is a case report. SETTING: The work was conducted in a university
      hospital. PATIENT: Whereas serum FSH (40.3 and 38.4 mIU/mL) and LH (35.7 and 31.7
      mIU/mL) levels were repeatedly around the menopausal range, serum anti-Mullerian
      hormone (4.50 and 4.36 ng/mL) levels and total counting of antral follicles (23
      and 18 follicles) remained normal. INTERVENTION: We aspirated antral-stage
      follicles and subsequently matured the oocytes in vitro. MAIN OUTCOME MEASURE: We
      assessed the competence of oocytes retrieved in a patient suffering from ovarian
      resistance to FSH. RESULTS: Aspiration of antral-stage follicles allowed the
      retrieval of 15 immature oocytes. Following IVM, 12 of them reached metaphase II.
      Seven embryos were obtained and three of them were transferred into the uterus.
      This patient became pregnant and delivered a healthy baby at term. CONCLUSIONS:
      We report the first pregnancy and live birth achieved using IVM in a woman whose
      ovaries were resistant to FSH. This approach was based on the remarkable normalcy
      of AMH and antral follicle measurements in this patient. Therefore, IVM is a
      viable alternative to egg donation for women suffering from resistance to FSH.
      Importantly, this condition should be looked for as it may lurk undetected in
      women wrongly diagnosed with ovarian failure.

PMID- 23956345
TI  - Elevated fetal adipsin/acylation-stimulating protein (ASP) in obese pregnancy:
      novel placental secretion via Hofbauer cells.
AB  - CONTEXT AND OBJECTIVE: Obesity in pregnancy is associated with increased risks of
      obesity in the offspring. We investigated the relationship between obesity in
      pregnancy and circulating maternal and fetal levels of adipose tissue-derived
      factors adipsin and acylation stimulating protein (ASP) in lean and obese
      mothers. DESIGN: Paired peripheral and cord blood samples were taken. Paired fat
      and placenta tissue were taken for explant culture. Media were assayed for
      secreted adipsin and ASP. Clinical parameters assayed included fasting insulin,
      glucose, and adipsin. SETTING: The study was conducted at a university hospital
      maternity unit. PATIENTS: Patients included 35 lean [body mass index (BMI) 19-25
      kg/m(2), mean age 32 years and 39 obese (BMI) > 30 kg/m(2), mean age 32.49 years]
      pregnant Caucasian women, delivered by cesarean section at term. MAIN OUTCOME
      MEASURE: Identification of placental macrophages [Hofbauer cells (HBCs)], as a
      source of adipsin and ASP was determined. RESULTS: HBCs secreted both adipsin and
      ASP. Cord levels of adipsin (1663.78 +/- 52.76 pg/mL) and ASP (354.48 +/- 17.17
      ng/mL) were significantly elevated in the offspring of obese mothers compared
      with their lean controls [1354.66 +/- 33.87 pg/mL and 302.63 +/- 14.98 ng/mL,
      respectively (P < .05 for both)]. Placentae from obese mothers released
      significantly more adipsin and ASP than placentae from lean mothers [546.0 +/- 44
      pg/mL . g vs 284.56 +/- 43 pg/mL . g and 5485.75 +/- 163.32 ng/mL . g vs 2399.16
      +/- 181.83 ng/mL . g, respectively (P < .05 for both)]. Circulating fetal adipsin
      and ASP positively correlated with maternal BMI (r = 0.611, P < .0001, and r =
      0.391, P < .05, respectively). Fetal adipsin correlated positively with maternal
      (r = 0.482, P < .01) and fetal homeostasis model assessment of insulin resistance
      (r = 0.465, P < .01). CONCLUSIONS: We demonstrate novel secretion of adipsin and
      ASP by placental HBCs.

PMID- 23956346
TI  - Assessing the clinical utility of a genetic risk score constructed using 49
      susceptibility alleles for type 2 diabetes in a Japanese population.
AB  - CONTEXT: Genome-wide association studies (GWASs) have identified over 60
      susceptibility loci for type 2 diabetes (T2D). Although the ability of previous
      genetic information (~40 loci) to discriminate between susceptible and
      nonsusceptible individuals is limited, the added benefit of updated genetic
      information has not been evaluated. OBJECTIVE: We assessed the clinical utility
      of GWAS-derived T2D susceptibility variants in a Japanese population. DESIGN AND
      SETTING: We conducted a cross-sectional case-control study. PARTICIPANTS: T2D
      cases (n = 2613) and controls (n = 1786) with complete genotype data for 49
      single-nucleotide polymorphisms (SNPs) were selected for analyses. OUTCOME
      MEASURES: We constructed genetic risk scores (GRSs) by summing the susceptibility
      alleles of 49 SNP loci for T2D (GRS-49) or 10 SNP loci with genome-wide
      significant association in previous Japanese studies (GRS-10) and examined the
      association of the GRSs with the disease by receiver operating characteristic
      analyses using a logistic regression model. RESULTS: The GRS-49 was significantly
      associated with T2D (P = 8.75 * 10(-45)). The area under the curve (AUC) for GRS
      49 alone (model 1) and for age, sex, and body mass index (model 2) was 0.624 and
      0.743, respectively. Addition of the GRS-49 to model 2 resulted in a small but
      significant increase in the AUC (DeltaAUC = 0.03, P = 7.99 * 10(-15)). Receiver
      operating characteristic AUC was greater for GRS-49 than for GRS-10 (0.624 vs
      0.603, P = .019), whereas the odds ratio per risk allele was smaller for GRS-49
      than for GRS-10 (GRS-49, 1.13, 95% confidence interval 1.11-1.15; GRS-10, 1.26,
      95% confidence interval = 1.22-1.31, P = 7.31 * 10(-10)). The GRS-49 was
      significantly associated with age at diagnosis in 1591 cases (beta = -0.199, P =
      .0069) and with fasting plasma glucose in 804 controls (beta = 0.009, P = 0.021).
      CONCLUSIONS: Updated genetic information slightly improves disease prediction
      ability but is not sufficiently robust for translation into clinical practice.

PMID- 23956347
TI  - Clinical review: Outcome of bilateral adrenalectomy in Cushing's syndrome: a
      systematic review.
AB  - BACKGROUND: The outcome of bilateral adrenalectomy (BADx) in patients with
      Cushing's syndrome (CS) is not well characterized. METHODS: A literature search
      was performed with the search terms "bilateral adrenalectomy" or "total
      adrenalectomy" and "Cushing's" or "Cushing." Immediate and long-term outcomes
      after BADx in CS were analyzed using descriptive statistics (median [range]).
      RESULTS: From 549 screened publications, 37 studies met inclusion criteria (1320
      patients, 82% having Cushing's disease [CD], 13% having ectopic CS, and 5% having
      primary adrenal hyperplasia). Surgical morbidity and mortality of BADx (23
      studies, 739 patients) were 18% (6-31) and 3% (0-15), respectively. In patients
      with CD, surgical mortality was below 1%. Although residual cortisol secretion
      due to accessory adrenal tissue or adrenal remnants was found in 3-34% (5
      studies, 236 patients), less than 2% had a relapse of CS. Symptoms of
      hypercortisolism (eg, hypertension, obesity, or depression) improved in the
      majority of the patients after BADx (7 studies, 195 patients). The number of
      adrenal crises per 100 patient-years was 9.3 (6 studies, 203 patients). Nelson's
      syndrome occurred in 21% (0-47) of the patients (24 studies, 768 patients).
      Mortality (23 studies, 690 patients) was 17% (0-88) at a follow-up of 41 months
      (14-294). Remarkably, 46% of the patients died in the first year after surgery.
      The median ages at death were 62 years (CD) and 53 years (ectopic CS).
      CONCLUSION: BADx is relatively safe and provides adequate success. Excess
      mortality within the first year after surgery suggests that intensive clinical
      care for patients after BADx is warranted.

PMID- 23956348
TI  - Skeletal muscle MnSOD, mitochondrial complex II, and SIRT3 enzyme activities are
      decreased in maternal obesity during human pregnancy and gestational diabetes
      mellitus.
AB  - CONTEXT: Insulin resistance and systemic oxidative stress are prominent features
      of pregnancies complicated by maternal obesity or gestational diabetes mellitus
      (GDM). The role of skeletal muscle oxidative stress or mitochondrial capacity in
      obese pregnant women or obese women with GDM is unknown. OBJECTIVE: We
      investigated whether obese pregnant women, compared with normal weight (NW)
      pregnant women, demonstrate decreased skeletal muscle mitochondrial enzyme
      activity and elevated markers of oxidative stress, and if these differences are
      more severe in obese women diagnosed with GDM. DESIGN: We measured mitochondrial
      enzyme activity and markers of oxidative stress in skeletal muscle tissue from NW
      pregnant women (n = 10), obese pregnant women with normal glucose tolerance (NGT;
      n = 10), and obese pregnant women with GDM (n = 8), undergoing cesarean delivery
      (~37 wk gestation). RESULTS: Electron transport complex-II and manganese
      superoxide dismutase (MnSOD) enzyme activities were decreased in obese-NGT and
      obese-GDM, compared with NW women. The glutathione redox ratio (GSH:GSSG) was
      decreased in obese-NGT and obese-GDM, indicative of increased oxidative stress.
      Mitochondrial sirtuin (SIRT)3 mRNA content and enzyme activity were lower in
      skeletal muscle of obese-NGT and obese-GDM women. Importantly, acetylation of
      MnSOD, a SIRT3 target, was increased in obese-NGT and obese-GDM vs NW women and
      was inversely correlated with SIRT3 activity (r = -0.603), suggesting a mechanism
      for reduced MnSOD activity. CONCLUSIONS: These data show that obese pregnant
      women demonstrate decreased skeletal muscle mitochondrial respiratory chain
      enzyme activity and decreased mitochondrial antioxidant defense. Furthermore,
      reduced skeletal muscle SIRT3 activity may play a role in the increased oxidative
      stress associated with pregnancies complicated by obesity.

PMID- 23956349
TI  - Low accuracy of tumor markers for diagnosing pancreatic neuroendocrine tumors in
      multiple endocrine neoplasia type 1 patients.
AB  - CONTEXT: The assessment of tumor markers for diagnosing pancreatic neuroendocrine
      tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised
      in the current guidelines but has never been validated for this purpose.
      OBJECTIVE: The objective of the study was to assess the diagnostic accuracy of
      chromogranin A (CgA), pancreatic polypeptide (PP), and glucagon for pNET in MEN1.
      DESIGN: This was a diagnostic study. SETTING: The study was conducted at Dutch
      university medical centers from 2008 to 2011, representing 90% of the total Dutch
      MEN1 population. PATIENTS AND METHODS: Patients for whom data on tumor markers in
      combination with the reference standard (ie, radiological imaging) were available
      between 2008 and 2011 were included. The reference standard for the presence of
      pNET was pathology or detection on magnetic resonance imaging, computed
      tomography, or endoscopic ultrasound confirmed on subsequent imaging,
      irrespective of modality at follow-up. MAIN OUTCOME MEASURES: The area under the
      receiver-operating characteristic curve (AUC), positive predictive value,
      negative predictive value, positive likelihood ratio, negative likelihood ratio,
      sensitivity, and specificity were calculated for each marker. RESULTS: For the
      analysis of PP, CgA, and glucagon, 73, 81, and 94 patients were available,
      respectively. The AUC for CgA was 0.48 [95% confidence interval (CI) 0.35-0.61]
      with a sensitivity 0.33 and a specificity 0.73; the AUC for glucagon was 0.58
      (95% CI 0.46-0.70) with a sensitivity 0.43 and a specificity 0.73; and the AUC
      for PP was 0.64 (95% CI 0.50-0.77) with a sensitivity 0.36 and a specificity
      0.74. Age, imaging modality, tumor size, and number did not influence the
      outcomes. CONCLUSION: The diagnostic accuracy of the tumor markers CgA, PP, and
      glucagon for pNET in MEN1 is low.

PMID- 23956350
TI  - Clinical review: Nonsurgical, image-guided, minimally invasive therapy for
      thyroid nodules.
AB  - CONTEXT: Nodular thyroid disease is very common. Most nodules are asymptomatic,
      are benign by fine-needle aspiration, remain stable, and can be followed by
      observation alone in the majority of the patients. Occasionally, nodules grow or
      cause symptoms requiring treatment. So far, surgery has been our main option for
      treatment. OBJECTIVE: In this review, we discuss nonsurgical, minimally invasive
      approaches for small thyroid masses, including indications, efficacy, side
      effects, and costs. EVIDENCE ACQUISITION: We selected recent publications related
      to minimally invasive thyroid techniques, with the focus on large-scale and
      preferably randomized studies, available via PubMed search in authors' files,
      using appropriate searches and keywords. MAIN FINDINGS: In large centers with
      experienced hands, minimally invasive approaches appear effective and safe. At
      present, percutaneous ethanol injection therapy is recommended for recurrent
      benign thyroid cysts. Either ultrasound-guided laser or radiofrequency ablation
      can be used for symptomatic solid nodules with normal or abnormal thyroid
      function. Microwave ablation and high-intensity focused ultrasound are newer
      approaches that need further clinical evaluation. These techniques have also been
      applied to recurrent locoregional cervical thyroid cancer with encouraging
      initial results, although still limited data. CONCLUSIONS: Surgery and
      radioiodine remain as conventional and established treatments for nodular
      goiters. However, the new image-guided minimally invasive approaches appear safe
      and effective and can be used to treat symptomatic or enlarging thyroid masses.

PMID- 23956351
TI  - Suppression of natural killer cell cytotoxicity in postpartum women: time course
      and potential mechanisms.
AB  - Little is known about the recovery of the immune system from normal pregnancy and
      whether the postpartum period is a uniquely adapted immune state. This report
      extends previous observations from our group of decreased natural killer (NK)
      cell cytotoxicity in the postpartum period. NK cytotoxicity was measured from 1
      week through 9 months postpartum. In addition, NK cytotoxicity was assayed in the
      presence or absence of pooled plasmas collected from either postpartum or
      nonpostpartum women. Samples of cells were stained for inhibitory receptors and
      analyzed by flow cytometry. NK cytotoxicity remained decreased in postpartum
      women compared to controls through the first 6 postpartum months, returned to
      normal levels by 9 months, and remained normal at 12 months. NK cytotoxicity
      during the first 6 months was further inhibited by the addition of pooled plasma
      to NK cultures from postpartum women, but the addition of pooled plasma from the
      control group did not affect that group's NK cultures. There were differences in
      inhibitory receptor staining between the two groups, with decreased CD158a and
      CD158b and increased NKG2A expression on postpartum NK cells during the first 3
      postpartum months. These data suggest that NK cytotoxicity postpartum inhibition
      lasts 6 months and is influenced by unidentified postpartum plasma components.
      The effect may also involve receptors on NK cells.

PMID- 23956352
TI  - F2-isoprostanes: a measure of oxidative stress in children receiving treatment
      for leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most prevalent and curable cancer among
      children and adolescents less than 15 years of age in the United States.
      Essential for cure of childhood ALL is prophylactic treatment of the central
      nervous system (CNS), with methotrexate (MTX) being the most widely used drug in
      this treatment. While CNS treatment has contributed to long-term disease-free
      survival, resulting declines in academic abilities have been reported. There is
      growing evidence that CNS treatment with MTX increases oxidative stress, a
      potential mechanism of CNS injury. This article reports changes in oxidative
      stress, measured by the biomarker F2-isoprostane (F2-IsoP), in the cerebrospinal
      fluid (CSF) in 47 children with ALL during the first 18 months of treatment. The
      number of CSF samples ranged from 5 to 14 during postinduction and from 1 to 9
      during continuation. Total doses of intrathecal MTX during postinduction were
      significantly correlated with the mean and highest concentrations of F2-IsoP
      during postinduction and the mean concentration of F2-IsoP during continuation.
      F2-IsoP concentrations during postinduction and continuation were higher in
      children who received more than six doses of intrathecal MTX. New therapies for a
      highly curable disease such as childhood leukemia have the potential to be
      individualized in the future, requiring reliable molecular and biochemical
      markers, such as oxidative stress indicators. Innovative use of biomarkers has
      the potential to increase our understanding of treatment-related toxicities and
      associated symptoms and to inform future therapeutic approaches for optimizing
      cure and quality of life among children with leukemia.

PMID- 23956353
TI  - HI-TENS reduces moderate-to-severe pain associated with most wound care
      procedures: a pilot study.
AB  - This study systematically examined pain associated with wound care procedures
      (WCPs) and evaluated the effectiveness of high-intensity transcutaneous
      electrical nerve stimulation (HI-TENS) for reducing this pain in a two-phase
      design. Phase 1 (N = 57) examined patient, wound, and procedural factors, as well
      as analgesic intake, associated with WCPs. Pain during the WCPs was rated on a 0
      10 numerical scale. Subjects reported a mean pain of 6.0 (standard deviation
      3.04) during Phase 1, with 43 (75.4%) subjects experiencing moderate or severe
      pain (i.e., >=4). Subjects who received opioid and/or nonopioid analgesia 1 hr
      before or during the WCPs (36.8%) reported significantly higher pain levels than
      those who had not received analgesia (p = .013). In Phase 2, 23 subjects with >=4
      pain during Phase 1 had HI-TENS applied to the area surrounding the wound during
      the WCPs. HI-TENS significantly reduced WCP pain by a mean of 2.0 (+/-2.31;
      effect size = 0.67; p = .001). This effect was significant for subjects with
      severe Phase 1 pain (i.e., >=8; effect size = 1.00; p = .007) but not for
      subjects with moderate Phase 1 pain (i.e., 4-7; effect size = 0.40; p = .053).
      These findings demonstrate that pain during WCPs is a significant problem, that
      nurses appropriately administer analgesics but these are not sufficient, and that
      using HI-TENS may further reduce pain, particularly in patients experiencing
      severe WCP pain.

PMID- 23956354
TI  - Human umbilical cord mesenchymal stem cells attenuate cisplatin-induced acute and
      chronic renal injury.
AB  - Mesenchymal stem cell is becoming a promising candidate in acute kidney injury
      (AKI). We first reported that human umbilical cord mesenchymal stem cells
      (hucMSCs) could ameliorate renal function in ischemic/reperfusion AKI rats, but
      the role of hucMSCs in cisplatin-induced acute and chronic injury has been
      demonstrated. More specifically, it is still unknown whether hucMSCs halt renal
      interstitial fibrosis. In this study, we investigated the effect of hucMSCs in
      cisplatin-induced kidney injury and explored the mechanism of action. Blood urea
      nitrogen (BUN) and creatinine (Cr) analyses showed amelioration of functional
      parameters in hucMSC-treated rats at early damage. Transplantation with hucMSCs
      promoted renal cell regeneration, inhibited cell apoptosis, abrogated
      inflammatory responses and protected mitochondria. Moreover, Masson's trichrome
      staining demonstrated reduced levels of fibrosis in kidney tissues of hucMSC
      treated rats at six and eight weeks after cisplatin injection. These results were
      corroborated by reduced collagen deposit, the ratio of Bax to Bcl-2 and
      transforming growth factor beta mRNA expression. Furthermore, hucMSCs prevented
      the epithelial-mesenchymal transition (EMT) in injury renal tissues, leading to
      the attenuation of chronic renal interstitial fibrosis. Taken together, our
      findings suggested that hucMSCs could decrease the kidney from development of
      later renal interstitial fibrosis by amelioration of early AKI.

PMID- 23956355
TI  - The relationship between environmental exposure to cadmium and lead and blood
      selenium concentration in randomly selected population of children inhabiting
      industrial regions of Silesian Voivodship (Poland).
AB  - This study aimed at determining the relationship between environmental exposure
      to lead (Pb) and cadmium (Cd) and blood selenium (Se) concentration in randomly
      selected population of children inhabiting the industrial regions of Silesian
      Voivodship, Poland. The study was conducted on a group of consecutive randomly
      selected 349 children aged below 15 years and inhabiting the industrial regions
      in Upper Silesia. The examined variables included whole blood Cd concentration
      (Cd-B), whole blood Pb concentration (Pb-B) and whole blood Se concentration (Se
      B). The concentration of Cd-B, Pb-B and Se-B in the studied group of children
      amounted to 0.26 +/- 0.14, 37.62 +/- 25.30 and 78.31 +/- 12.82 MUg/L,
      respectively. In the entire examined group a statistically significant negative
      linear relationship was noted between Pb-B and Se-B (r = -0.12, p < 0.05). Also,
      a statistically insignificant negative correlation was detected between Cd-B and
      Se-B (r = -0.02, p > 0.05) and a statistically insignificant positive correlation
      between Pb-B and Cd-B (r = 0.08, p > 0.05). A multivariate backward stepwise
      regression analysis demonstrated that in the studied group of children higher Pb
      B and a more advanced age-represented independent risk factors for a decreased Se
      B. Environmental exposure to Pb may represent an independent risk factor for Se
      deficit in blood of the studied population of children. In children, the lowered
      Se-B may create one of the mechanisms in which Pb unfavourably affects human
      body. 

PMID- 23956356
TI  - Early child care and illness among preschoolers.
AB  - The majority of young American children regularly spend time in nonparental care
      settings. Such arrangements are associated with their experiences of common
      childhood illnesses. Why this linkage exists, how it varies across the
      socioeconomic spectrum, and whether it has implications for how parents arrange
      care are all important theoretical and policy issues. In this study, therefore,
      we applied a fixed-effects design within structural equation modeling to data
      from the National Institute of Child Health and Human Development Study of Early
      Child Care and Youth Development (n = 1,364). Results revealed that children were
      sick more often when cared for in a center and had more peer exposure in their
      primary care settings, although this latter association was observed only among
      children of the least educated mothers. Net of such factors, children in multiple
      arrangements did not experience more illness, but illnesses tended to decrease
      subsequent peer exposure as parents changed children's care arrangements. 

PMID- 23956357
TI  - Mothers' union histories and the mental and physical health of adolescents born
      to unmarried mothers.
AB  - As nonmarital childbearing becomes a dominant pathway to family formation,
      understanding its long-term consequences for children's well-being is
      increasingly important. Analysis of linked mother-child data from the 1979
      National Longitudinal Survey of Youth indicates a negative association of having
      been born to a never-married mother with adolescent self-assessed health but not
      with depressive symptoms. We also consider the role of mothers' subsequent union
      histories in shaping the adolescent health outcomes of youth born to unmarried
      mothers. With two exceptions, unmarried mothers' subsequent unions appear to have
      little consequence for the health of their offspring during adolescence.
      Adolescents whose mothers subsequently married and remained with their biological
      fathers reported better health, yet adolescents whose mothers continuously
      cohabited with their biological fathers without subsequent marriage reported
      worse adolescent mental health compared with adolescents whose mothers remained
      continually unpartnered. 

PMID- 23956358
TI  - Do family dinners reduce the risk for early adolescent substance use? A
      propensity score analysis.
AB  - The risks of early adolescent substance use on health and well-being are well
      documented. In recent years, several experts have claimed that a simple
      preventive measure for these behaviors is for families to share evening meals. In
      this study, we use data from the 1997 National Longitudinal Study of Youth (n =
      5,419) to estimate propensity score models designed to match on a set of
      covariates and predict early adolescent substance use frequency and initiation.
      The results indicate that family dinners are not generally associated with
      alcohol or cigarette use or with drug use initiation. However, a continuous
      measure of family dinners is modestly associated with marijuana frequency, thus
      suggesting a potential causal impact. These results show that family dinners may
      help prevent one form of substance use in the short term but do not generally
      affect substance use initiation or alcohol and cigarette use. 

PMID- 23956359
TI  - Zinc oxide influences intestinal integrity, the expressions of genes associated
      with inflammation and TLR4-myeloid differentiation factor 88 signaling pathways
      in weanling pigs.
AB  - This study explored whether zinc oxide (ZnO) supplementation could alleviate
      weanling-induced intestinal injury through TLR and NOD-like receptor signaling
      pathways. Twelve early-weanling piglets were allotted to two dietary treatments
      (control vs 2200 mg Zn/kg from ZnO) for 1 wk. The results showed that
      supplemental ZnO improved daily gain and feed intake, decreased post weaning
      scour scores, increased villus height and villus height:crypt depth ratio at the
      jejunal mucosa, and decreased diamine oxidase activity and endotoxin
      concentration in plasma. The intestinal mRNA levels of TLR4 and its downstream
      signals, including MyD88, IL-1 receptor-associated kinase 1 and TNF-alpha
      receptor-associated factor 6, were decreased, and the expressions of intestinal
      pro-inflammatory cytokines and chemokines were decreased simultaneously in the
      ZnO-supplemented piglets. Although NF-kappaB p65 mRNA abundance was not affected
      by ZnO supplementation, NF-kappaB p65 protein expression was down-regulated by
      ZnO. However, ZnO supplementation had no effect on intestinal expressions of NOD1
      and NOD2, and their adaptor molecule receptor-interacting serine/threonine
      protein kinase 2, as well as protein expressions of caspase-3 and heat shock
      protein 70. The results indicated that the protective effects of ZnO on
      intestinal integrity were closely related to decreasing the expressions of genes
      associated with inflammation through inhibiting the TLR4-MyD88 signaling
      pathways. 

PMID- 23956360
TI  - eComment. Ascending-descending aortic bypass in patients with complex aortic
      coarctation.

PMID- 23956361
TI  - eComment. Intraoperative glycaemic control in cardiac surgical patients.

PMID- 23956362
TI  - eComment. Potential therapeutic agents in vasoplegic syndrome after cardiac
      surgery.

PMID- 23956363
TI  - eComment. Total surgical aortic arch replacement.

PMID- 23956364
TI  - eComment. Extracorporeal membrane oxygenation for deep accidental hypothermia.

PMID- 23956365
TI  - eComment. Nuss pectus excavatum repair: friend or foe?

PMID- 23956366
TI  - eComment. Aneurysm of the internal mammary artery may imitate a mediastinal mass.

PMID- 23956367
TI  - eReply. Aneurysm of the internal mammary artery may imitate a mediastinal mass.

PMID- 23956369
TI  - A new proxy measure for state-level gun ownership in studies of firearm injury
      prevention.
AB  - Since many states are considering gun control laws, researchers need reliable
      data on rates of gun ownership at the state level. Survey measures of gun
      ownership in all 50 states, however, are only available for 3 years, and no state
      level data have been collected since 2004. Consequently, the National Research
      Council has declared the development of a valid proxy that can be constructed
      from accessible, annual, state-level data to be a priority. While such a proxy
      does exist (the proportion of suicides in a state committed using a gun (FS/S),
      its correlation with state estimates of gun ownership in recent years is only
      0.80. Using state-level data for the years 2001, 2002 and 2004, we developed an
      improved proxy for state-level gun ownership that uses FS/S (firearm suicides
      divided by all suicides) and also the per capita number of hunting licenses. We
      validated this measure using data from surveys of gun ownership conducted in 48
      states during 1996 and 1999, and in 21 states during 1995-1998. Adding per capita
      hunting licenses to the proxy increased its correlation with survey-measured gun
      ownership from 0.80 to 0.95. The correlations of the new proxy with gun ownership
      in the two validation studies were 0.95 and 0.97. We conclude that the
      combination of FS/S and per capita hunting licenses improves substantially upon
      FS/S alone. This new proxy is easily computed from data that are available
      annually by state and may be useful for investigating the effect of gun
      prevalence on firearm-related morbidity and mortality. 

PMID- 23956370
TI  - Evaluation of a school-based violence prevention media literacy curriculum.
AB  - PURPOSE: Evaluate whether Beyond Blame, a violence prevention media literacy
      curriculum, is associated with improved knowledge, beliefs and behaviours related
      to media use and aggression. METHODS: Using a quasi-experimental design, from
      2007 to 2008, teachers from schools across Southern California administered the
      curriculum with or without training or served as controls. Students were tested
      before and after the curriculum was implemented, and during the fall semester of
      the next academic year. Multivariate hierarchical regression was used to compare
      changes from baseline to follow-up between the intervention and control groups.
      RESULTS: Compared with controls, at the first post-test, students in the trained
      and untrained groups reported increased knowledge of five core concepts/key
      questions of media literacy, increased self-rated exposure to media violence, as
      well as stronger beliefs that media violence affects viewers and that people can
      protect themselves by watching less. Regarding behaviours, controls were more
      likely to report >=8 h of media consumption at the second post-test than at
      baseline (OR=2.11; 95% CI 1.13 to 3.97), pushing or shoving another student
      (OR=2.16; 95% CI 1.16 to 4.02) and threatening to hit or hurt someone (OR=2.32;
      95% CI 1.13 to 4.78). In comparison, there was no increase in these behaviours in
      the trained and untrained groups. CONCLUSIONS: This study suggests media literacy
      can be feasibly integrated into schools as an approach to improving critical
      analysis of media, media consumption and aggression. Changing the way youth
      engage media may impact many aspects of health, and an important next step will
      be to apply this framework to other topics.

PMID- 23956371
TI  - Controlling for exposure changes the relationship between ethnicity, deprivation
      and injury: an observational study of child pedestrian injury rates in London.
AB  - BACKGROUND: Research has suggested that inequalities in risk exposure may help
      explain identified ethnic inequalities in child pedestrian injury risk. However,
      addressing risk exposure in epidemiological research presents theoretical and
      methodological challenges. This article conceptualises the risk of child
      pedestrian injury as related to both exposure levels (the quantity of time
      children spend as pedestrians) and the probability of a hazard where that
      exposure takes place (the quality of the road environment). OBJECTIVE: To
      investigate the sensitivity of results on ethnic inequalities in child pedestrian
      injury risk in London to control for exposure and hazard levels. METHODS: Using
      police records of injury 2000-2009, we modelled the relationship between
      ethnicity, deprivation and child pedestrian injury rates in London using
      characteristics of the road environment to control for hazard levels and
      restricting the analysis to the time of the weekday morning commute (7.00-9.00
      am), when most children must make a journey to school, to control for exposure
      levels. RESULTS: Controlling for risk exposure in this way fundamentally changed
      the nature of the relationship between ethnicity, deprivation and child
      pedestrian injury. During the time of the morning commute to school, 'Black'
      children were found to have higher pedestrian injury rates in the least-deprived
      areas. CONCLUSIONS: To inform effective strategies for reducing injury
      inequality, it is vital that exposure to risk is both acknowledged and
      considered.

PMID- 23956372
TI  - Is disability really a protective factor for burns in Kurdish preschool children?

PMID- 23956373
TI  - Risk factors and clinical characteristics of patients with qnr-positive
      Klebsiella pneumoniae bacteraemia.
AB  - OBJECTIVES: Plasmid-mediated quinolone resistance (PMQR) caused by qnr genes has
      been known for 15 years. Information about global distribution and prevalence of
      qnr genes is abundant, but clinical information concerning infections produced by
      these isolates and risk factors for their acquisition is limited. METHODS:
      Klebsiella pneumoniae blood isolates (n = 227) from a 1 year prospective cohort
      of patients in Taiwan were studied. MICs of quinolones were determined for all
      isolates, and multiplex PCR for the presence of PMQR genes and DNA gyrase
      mutations was applied to all 24 isolates with ciprofloxacin MICs >= 0.12 mg/L and
      a control group of 72 isolates with MICs <= 0.06 mg/L. RESULTS: All qnr isolates
      were in the group with ciprofloxacin MICs >= 0.12 mg/L, constituting 9.4% of
      tested isolates and 3.9% (qnrB 2.6% and qnrS 1.3%) of total isolates. aac(6')-Ib
      cr and qepA were not found. Risk factors for qnr included nosocomial infection,
      bedridden status, surgery within 3 months, non-K1/K2 serotypes and prior
      antimicrobial use. Ciprofloxacin MIC >= 0.12 mg/L was associated with prior
      quinolone use; in contrast, prior cephalosporin use was more closely linked to
      the presence of qnr. Fourteen-day mortality was similar in patients infected with
      qnr-positive versus qnr-negative isolates, but there was a trend for increased in
      hospital mortality in patients infected with qnr-positive isolates. CONCLUSIONS:
      In K. pneumoniae blood isolates collected at a hospital in Taiwan, the overall
      prevalence of qnr genes was 3.9%. Prior quinolone use was linked to increased
      ciprofloxacin MIC, but not with the prevalence of qnr, which was most strongly
      linked to exposure to other antimicrobials, especially cephalosporins.

PMID- 23956374
TI  - Antiretroviral medication prescribing errors are common with hospitalization of
      HIV-infected patients.
AB  - OBJECTIVES: Errors in prescribing antiretroviral therapy (ART) often occur with
      the hospitalization of HIV-infected patients. The rapid identification and
      prevention of errors may reduce patient harm and healthcare-associated costs.
      METHODS: A retrospective review of hospitalized HIV-infected patients was carried
      out between 1 January 2009 and 31 December 2011. Errors were documented as
      omission, underdose, overdose, duplicate therapy, incorrect scheduling and/or
      incorrect therapy. The time to error correction was recorded. Relative risks
      (RRs) were computed to evaluate patient characteristics and error rates. RESULTS:
      A total of 289 medication errors were identified in 146/416 admissions (35%). The
      most common was drug omission (69%). At an error rate of 31%, nucleoside reverse
      transcriptase inhibitors were associated with an increased risk of error when
      compared with protease inhibitors (RR 1.32; 95% CI 1.04-1.69) and co-formulated
      drugs (RR 1.59; 95% CI 1.19-2.09). Of the errors, 31% were corrected within the
      first 24 h, but over half (55%) were never remedied. Admissions with an omission
      error were 7.4 times more likely to have all errors corrected within 24 h than
      were admissions without an omission. Drug interactions with ART were detected on
      51 occasions. For the study population (n = 177), an increased risk of admission
      error was observed for black (43%) compared with white (28%) individuals (RR
      1.53; 95% CI 1.16-2.03) but no significant differences were observed between
      white patients and other minorities or between men and women. CONCLUSION: Errors
      in inpatient ART were common, and the majority were never detected. The most
      common errors involved omission of medication, and nucleoside reverse
      transcriptase inhibitors had the highest rate of prescribing error. Interventions
      to prevent and correct errors are urgently needed.

PMID- 23956376
TI  - Description of the metallo-beta-lactamase GIM-1 in Acinetobacter pittii.
AB  - OBJECTIVES: To characterize the mechanisms involved in the reduced carbapenem
      susceptibility of five Acinetobacter pittii strains isolated from different
      regions of Germany. METHODS: The strains were analysed by susceptibility testing,
      phenotypic tests for metallo-beta-lactamase production, sequencing of the
      integron structure and strain typing by PFGE, as well as multilocus sequence
      typing (MLST) and plasmid analysis by S1 restriction and hybridization. RESULTS:
      Despite GIM-1 production, the MICs of imipenem were only 4 mg/L for four strains
      and some methods of phenotypic MBL detection failed. According to PFGE and MLST,
      the strains belonged to four different clones, but blaGIM-1 was present in
      identical integron structures in all strains and carried on plasmids of ~60 kb.
      CONCLUSIONS: For the first time, GIM-1 has been demonstrated in A. pittii. This
      resistance mechanism has previously been reported only in Enterobacteriaceae and
      Pseudomonas aeruginosa. As GIM-1 was found in strains with diverse clonal
      backgrounds, but encoded on plasmids of a similar size, further spread among
      Acinetobacter spp. seems possible. The detection of GIM-1 production might be
      challenging in some strains due to the low MICs of carbapenems.

PMID- 23956375
TI  - Liposomal resiquimod for the treatment of Leishmania donovani infection.
AB  - OBJECTIVES: The imidazoquinoline family of drugs are Toll-like receptor 7/8
      agonists that have previously been used in the treatment of cutaneous
      leishmaniasis. Because of the hydrophobic nature of imidazoquinolines, they are
      traditionally not administered systemically for the treatment of visceral
      leishmaniasis. We formulated liposomal resiquimod, an imidazoquinoline, for the
      systemic treatment of visceral leishmaniasis. METHODS: By using lipid film
      hydration with extrusion, we encapsulated resiquimod in liposomes. These
      liposomes were then injected intravenously to treat BALB/c mice infected with
      Leishmania donovani. RESULTS: Treatment with liposomal resiquimod significantly
      decreased the parasite load in the liver, spleen and bone marrow. In addition,
      resiquimod treatment increased interferon-gamma and interleukin-10 production in
      an antigen recall assay. Resiquimod was shown to be non-toxic in histology and in
      vitro culture experiments. CONCLUSIONS: FDA-approved resiquimod, in a liposomal
      formulation, displays promising results in treating visceral leishmaniasis.

PMID- 23956377
TI  - In vitro formation of acetylmorphine from morphine and aspirin in postmortem
      gastric contents and deionized water.
AB  - Forensic toxicologists consider detection of 6-acetylmorphine (6-AM) definitive
      evidence of heroin abuse. This study investigated the possibility that aspirin,
      when in solution with morphine, may acetylate morphine to produce acetylmorphine
      (AM). Morphine sulfate-extended release tablets (15 mg) and aspirin (325 mg)
      tablets were incubated in 50 mL postmortem gastric contents or deionized water at
      37 degrees C. One-milliliter aliquots were taken at timed intervals, extracted by
      solid-phase extraction, derivatized and analyzed by the gas chromatograph with a
      mass selective detector. Both 3- and 6-AM were detected in samples containing
      morphine and aspirin in combination; no heroin was detected. Production of AM was
      pH dependent with optimal formation at pH >=4. In gastric contents,
      concentrations of 3-AM exceeded that of 6-AM by ~10-fold. Production of 3-AM in
      gastric contents was approximately twice as high as it was in water, while matrix
      did not appear to affect 6-AM production. Urine specimens (10,602) assayed at a
      pain management laboratory and postmortem cases (>6,000) were investigated for in
      vivo formation of AM. Three cases exhibited unexplained 6-AM results. These data
      indicate that in vivo formation of 6-AM from the co-administration of aspirin and
      morphine, if it happens, is quite rare. In instances where this is suspected, 3
      AM should be monitored. 

PMID- 23956380
TI  - Is acupuncture a risk factor for hepatitis C virus infection?

PMID- 23956381
TI  - Neuroanatomical basis for acupuncture point PC8 in the rat: neural tracing study
      with cholera toxin subunit B.
AB  - OBJECTIVES: This study was performed to investigate the innervations related to
      acupuncture point PC8 in rats using a neural tracing technique. METHODS: After 6
      MUL of 1% cholera toxin subunit B (CTB) was injected into the site between the
      second and third metacarpal bone in rats, a corresponding site to acupuncture
      point PC8 in the human body, CTB labelling was examined with immunofluorescence
      and immunohistochemistry in the dorsal root ganglia (DRG), spinal cord and
      brainstem. RESULTS: All CTB labelling appeared on the ipsilateral side of the
      injection. The labelled sensory neurons distributed from cervical (C)6 to
      thoracic (T)1 DRG, while the labelled motor neurons were located on the
      dorsolateral part of the spinal ventral horn ranging from the C6 to T1 segments.
      In addition, the transganglionically-labelled axonal terminals were found to be
      dense in the medial part of laminae 3-4 from C6 to the T1 spinal dorsal horn, as
      far as in the cuneate nucleus. CONCLUSIONS: These results indicate that sensory
      and motor neurons associated with PC8 distribute in a distinct segmental pattern.
      The sensory information from PC8 could be transganglionically transported to the
      spinal dorsal horn and cuneate nucleus.

PMID- 23956382
TI  - MRI evaluation of metal acupuncture needles.
AB  - OBJECTIVE: To evaluate the MR compatibility of three metal acupuncture needles (a
      standard stainless steel needle, a gold needle and an austenitic stainless steel
      needle) by comparing their imaging artefacts, radiofrequency heating effects and
      ease of operation. METHODS: The MRI artefacts of the three metal needles were
      first evaluated by placing them in an agar gel phantom and performing MRI of the
      phantom. The increase in temperature during MRI was recorded using an MR
      compatible fibreoptic thermometer. MRI of acupuncture at SP6 was performed using
      the MR-compatible gold needle and the austenitic stainless steel needle. RESULTS:
      The standard stainless steel acupuncture needle produced large imaging artefacts
      on MRI. The gold needle was superior for MRI but not rigid enough for some
      clinical applications such as scalp acupuncture. The austenitic stainless steel
      needle is non-ferromagnetic and compatible with MRI. None of these acupuncture
      needles introduced radiofrequency heating during MRI. CONCLUSIONS: The evaluation
      of MR compatibility showed that gold and austenitic stainless steel needles are
      MR-compatible and therefore can be used for MRI of acupuncture.

PMID- 23956383
TI  - Comparison of PCR versus culture for detection of Mycobacterium bovis after
      experimental inoculation of various matrices held under environmental conditions
      for extended periods.
AB  - The purpose of this study was to compare the performance of a molecular detection
      technique (nested PCR) with that of mycobacterial culture in the detection of
      Mycobacterium bovis DNA in a set of 687 samples of experimentally inoculated
      environmental substrates (hay, soil, corn, water) exposed to natural weather
      conditions in Michigan. Four replicates of each substrate were used; half were
      autoclaved for sterilization, all were inoculated with 50,000 CFU of M. bovis
      isolated from Michigan livestock, and all were placed in outdoor enclosures, with
      half under shade and the other half exposed to direct sunlight. Samples were
      tested for the presence of M. bovis during one 12-month period, with monthly
      sample testing and during three 12-week periods (winter, spring, summer) with
      weekly sample testing. Samples were subjected to mycobacterial culture for
      isolation of M. bovis and a nested PCR with two primer sets targeting IS6110 to
      detect M. bovis DNA. In 128 samples tested during the 12-month period, M. bovis
      was not detectable by culture after 2 months but M. bovis DNA was detectable by
      PCR for at least 7 months. Of the 559 samples tested during the 12-week periods,
      PCR detected M. bovis DNA for up to 88 days in all of the sample types. There
      were no significant differences in the detection of M. bovis between shade and
      sun samples or between sterile and unsterilized samples, regardless of the
      detection method (PCR or culture). For use in epidemiologic investigations, the
      PCR assay was more rapid than mycobacterial culture, was not hindered by
      contaminating organisms, and detected M. bovis DNA in environment samples much
      longer after initial contamination than mycobacterial culture did. 

PMID- 23956384
TI  - Temporal changes and altitudinal distribution of aerobic anoxygenic phototrophs
      in mountain lakes.
AB  - Aerobic anoxygenic phototrophs (AAPs) are bacteriochlorophyll a-containing
      microorganisms that use organic substrates for growth but can supplement their
      energy requirements with light. They have been reported from various marine and
      limnic environments; however, their ecology remains largely unknown. Here
      infrared epifluorescence microscopy was used to monitor temporal changes in AAPs
      in the alpine lake Gossenkollesee, located in the Tyrolean Alps, Austria. AAP
      abundance was low (10(3) cells ml(-1)) until mid-July and reached a maximum of
      ~1.3 * 10(5) cells ml(-1) (29% of all prokaryotes) in mid-September. We compared
      the studied lake with other mountain lakes located across an altitudinal gradient
      (913 to 2,799 m above sea level). The concentration of dissolved organic carbon
      and water transparency seem to be the main factors influencing AAP abundance
      during the seasonal cycle as well as across the altitudinal gradient. While the
      AAP populations inhabiting the alpine lakes were composed of intensely pigmented
      large rods (5 to 12 MUm), the lakes below the tree line were inhabited by a
      variety of smaller morphotypes. Analysis of pufM diversity revealed that AAPs in
      Gossenkollesee were almost exclusively Sphingomonadales species, which indicates
      that AAP communities inhabiting alpine lakes are relatively homogeneous compared
      to those in low-altitude lakes. 

PMID- 23956385
TI  - Integrating terminal truncation and oligopeptide fusion for a novel protein
      engineering strategy to improve specific activity and catalytic efficiency:
      alkaline alpha-amylase as a case study.
AB  - In this work, we integrated terminal truncation and N-terminal oligopeptide
      fusion as a novel protein engineering strategy to improve specific activity and
      catalytic efficiency of alkaline alpha-amylase (AmyK) from Alkalimonas
      amylolytica. First, the C terminus or N terminus of AmyK was partially truncated,
      yielding 12 truncated mutants, and then an oligopeptide (AEAEAKAKAEAEAKAK) was
      fused at the N terminus of the truncated AmyK, yielding another 12 truncation
      fusion mutants. The specific activities of the truncation-fusion mutants
      AmyKDeltaC500-587::OP and AmyKDeltaC492-587::OP were 25.5- and 18.5-fold that of
      AmyK, respectively. The kcat/Km was increased from 1.0 * 10(5) liters . mol(-1) .
      s(-1) for AmyK to 30.6 * and 23.2 * 10(5) liters . mol(-1) . s(-1) for
      AmyKDeltaC500-587::OP and AmyKDeltaC492-587::OP, respectively. Comparative
      analysis of structure models indicated that the higher flexibility around the
      active site may be the main reason for the improved catalytic efficiency. The
      proposed terminal truncation and oligopeptide fusion strategy may be effective to
      engineer other enzymes to improve specific activity and catalytic efficiency. 

PMID- 23956386
TI  - A fungal insecticide engineered for fast per os killing of caterpillars has high
      field efficacy and safety in full-season control of cabbage insect pests.
AB  - Fungal insecticides developed from filamentous pathogens of insects are notorious
      for their slow killing action through cuticle penetration, depressing commercial
      interest and practical application. Genetic engineering may accelerate their
      killing action but cause ecological risk. Here we show that a Beauveria bassiana
      formulation, HV8 (BbHV8), engineered for fast per os killing of caterpillars by
      an insect midgut-acting toxin (Vip3Aa1) overexpressed in conidia has both high
      field efficacy and safety in full-season protection of cabbage from the damage of
      an insect pest complex dominated by Pieris rapae larvae, followed by Plutella
      xylostella larvae and aphids. In two fields repeatedly sprayed during summer,
      BbHV8 resulted in overall mean efficacies of killing of 71% and 75%, which were
      similar or close to the 70% and 83% efficacies achieved by commercially
      recommended emamectin benzoate but much higher than the 31% and 48% efficacies
      achieved by the same formulation of the parental wild-type strain (WT). Both
      BbHV8 and WT sprays exerted no adverse effect on a nontarget spider community
      during the trials, and the sprays did not influence saprophytic fungi in soil
      samples taken from the field plots during 4 months after the last spray.
      Strikingly, BbHV8 and the WT showed low fitness when they were released into the
      environment because both were decreasingly recovered from the field lacking
      native B. bassiana strains (undetectable 5 months after the spray), and the
      recovered isolates became much less tolerant to high temperature and UV-B
      irradiation. Our results highlight for the first time that a rationally
      engineered fungal insecticide can compete with a chemical counterpart to combat
      insect pests at an affordable cost and with low ecological risk. 

PMID- 23956387
TI  - Benchmarking various green fluorescent protein variants in Bacillus subtilis,
      Streptococcus pneumoniae, and Lactococcus lactis for live cell imaging.
AB  - Green fluorescent protein (GFP) offers efficient ways of visualizing promoter
      activity and protein localization in vivo, and many different variants are
      currently available to study bacterial cell biology. Which of these variants is
      best suited for a certain bacterial strain, goal, or experimental condition is
      not clear. Here, we have designed and constructed two "superfolder" GFPs with
      codon adaptation specifically for Bacillus subtilis and Streptococcus pneumoniae
      and have benchmarked them against five other previously available variants of GFP
      in B. subtilis, S. pneumoniae, and Lactococcus lactis, using promoter-gfp
      fusions. Surprisingly, the best-performing GFP under our experimental conditions
      in B. subtilis was the one codon optimized for S. pneumoniae and vice versa. The
      data and tools described in this study will be useful for cell biology studies in
      low-GC-rich Gram-positive bacteria. 

PMID- 23956388
TI  - Methanosarcinaceae and acetate-oxidizing pathways dominate in high-rate
      thermophilic anaerobic digestion of waste-activated sludge.
AB  - This study investigated the process of high-rate, high-temperature methanogenesis
      to enable very-high-volume loading during anaerobic digestion of waste-activated
      sludge. Reducing the hydraulic retention time (HRT) from 15 to 20 days in
      mesophilic digestion down to 3 days was achievable at a thermophilic temperature
      (55 degrees C) with stable digester performance and methanogenic activity. A
      volatile solids (VS) destruction efficiency of 33 to 35% was achieved on waste
      activated sludge, comparable to that obtained via mesophilic processes with low
      organic acid levels (<200 mg/liter chemical oxygen demand [COD]). Methane yield
      (VS basis) was 150 to 180 liters of CH4/kg of VS(added). According to 16S rRNA
      pyrotag sequencing and fluorescence in situ hybridization (FISH), the
      methanogenic community was dominated by members of the Methanosarcinaceae, which
      have a high level of metabolic capability, including acetoclastic and
      hydrogenotrophic methanogenesis. Loss of function at an HRT of 2 days was
      accompanied by a loss of the methanogens, according to pyrotag sequencing. The
      two acetate conversion pathways, namely, acetoclastic methanogenesis and
      syntrophic acetate oxidation, were quantified by stable carbon isotope ratio mass
      spectrometry. The results showed that the majority of methane was generated by
      nonacetoclastic pathways, both in the reactors and in off-line batch tests,
      confirming that syntrophic acetate oxidation is a key pathway at elevated
      temperatures. The proportion of methane due to acetate cleavage increased later
      in the batch, and it is likely that stable oxidation in the continuous reactor
      was maintained by application of the consistently low retention time.

PMID- 23956389
TI  - RNase III is required for actinomycin production in Streptomyces antibioticus.
AB  - Using insertional mutagenesis, we have disrupted the RNase III gene, rnc, of the
      actinomycin-producing streptomycete, Streptomyces antibioticus. Disruption was
      verified by Southern blotting. The resulting strain grows more vigorously than
      its parent on actinomycin production medium but produces significantly lower
      levels of actinomycin. Complementation of the rnc disruption with the wild-type
      rnc gene from S. antibioticus restored actinomycin production to nearly wild-type
      levels. Western blotting experiments demonstrated that the disruptant did not
      produce full-length or truncated forms of RNase III. Thus, as is the case in
      Streptomyces coelicolor, RNase III is required for antibiotic production in S.
      antibioticus. No differences in the chemical half-lives of bulk mRNA were
      observed in a comparison of the S. antibioticus rnc mutant and its parental
      strain. 

PMID- 23956390
TI  - The MAP kinase Slt2 is involved in vacuolar function and actin remodeling in
      Saccharomyces cerevisiae mutants affected by endogenous oxidative stress.
AB  - Oxidative stress causes transient actin cytoskeleton depolarization and also
      provokes vacuole fragmentation in wild-type cells. Under conditions of oxidative
      stress induced by hydrogen peroxide, the Slt2 protein is required to repolarize
      the actin cytoskeleton and to promote vacuole fusion. In this study, we show that
      grx3 grx4 and grx5 mutants are cellular models of endogenous oxidative stress.
      This stress is the result of alterations in iron homeostasis that lead to
      impairment of vacuolar function and also to disorganization of the actin
      cytoskeleton. Slt2 overexpression suppresses defects in vacuolar function and
      actin cytoskeleton organization in the grx3 grx4 mutant. Slt2 exerts this effect
      independently of the intracellular levels of reactive oxygen species (ROS) and of
      iron homeostasis. The deletion of SLT2 in the grx3 grx4 mutant results in
      synthetic lethality related to vacuolar function with substantial vacuole
      fragmentation. The observation that both Vps4 and Vps73 (two proteins related to
      vacuole sorting) suppress vacuole fragmentation and actin depolarization in the
      grx3 grx4 slt2 triple mutant strengthens the hypothesis that Slt2 plays a role in
      vacuole homeostasis related to actin dynamics. Here we show that in sod1, grx5,
      and grx3 grx4 slt2 mutants, all of which are affected by chronic oxidative
      stress, the overexpression of Slt2 favors vacuole fusion through a mechanism
      dependent on an active actin cytoskeleton. 

PMID- 23956391
TI  - Subtyping of a large collection of historical Listeria monocytogenes strains from
      Ontario, Canada, by an improved multilocus variable-number tandem-repeat analysis
      (MLVA).
AB  - Listeria monocytogenes is responsible for severe and often fatal food-borne
      infections in humans. A collection of 2,421 L. monocytogenes isolates originating
      from Ontario's food chain between 1993 and 2010, along with Ontario clinical
      isolates collected from 2004 to 2010, was characterized using an improved
      multilocus variable-number tandem-repeat analysis (MLVA). The MLVA method was
      established based on eight primer pairs targeting seven variable-number tandem
      repeat (VNTR) loci in two 4-plex fluorescent PCRs. Diversity indices and
      amplification rates of the individual VNTR loci ranged from 0.38 to 0.92 and from
      0.64 to 0.99, respectively. MLVA types and pulsed-field gel electrophoresis
      (PFGE) patterns were compared using Comparative Partitions analysis involving 336
      clinical and 99 food and environmental isolates. The analysis yielded Simpson's
      diversity index values of 0.998 and 0.992 for MLVA and PFGE, respectively, and
      adjusted Wallace coefficients of 0.318 when MLVA was used as a primary subtyping
      method and 0.088 when PFGE was a primary typing method. Statistical data analysis
      using BioNumerics allowed for identification of at least 8 predominant and
      persistent L. monocytogenes MLVA types in Ontario's food chain. The MLVA method
      correctly clustered epidemiologically related outbreak strains and separated
      unrelated strains in a subset analysis. An MLVA database was established for the
      2,421 L. monocytogenes isolates, which allows for comparison of data among
      historical and new isolates of different sources. The subtyping method coupled
      with the MLVA database will help in effective monitoring/prevention approaches to
      identify environmental contamination by pathogenic strains of L. monocytogenes
      and investigation of outbreaks. 

PMID- 23956392
TI  - Fluorescence-based bacterial bioreporter for specific detection of methyl halide
      emissions in the environment.
AB  - Methyl halides are volatile one-carbon compounds responsible for substantial
      depletion of stratospheric ozone. Among them, chloromethane (CH3Cl) is the most
      abundant halogenated hydrocarbon in the atmosphere. Global budgets of methyl
      halides in the environment are still poorly understood due to uncertainties in
      their natural sources, mainly from vegetation, and their sinks, which include
      chloromethane-degrading bacteria. A bacterial bioreporter for the detection of
      methyl halides was developed on the basis of detailed knowledge of the physiology
      and genetics of Methylobacterium extorquens CM4, an aerobic alphaproteobacterium
      which utilizes chloromethane as the sole source of carbon and energy. A plasmid
      construct with the promoter region of the chloromethane dehalogenase gene cmuA
      fused to a promotorless yellow fluorescent protein gene cassette resulted in
      specific methyl halide-dependent fluorescence when introduced into M. extorquens
      CM4. The bacterial whole-cell bioreporter allowed detection of methyl halides at
      femtomolar levels and quantification at concentrations above 10 pM (approximately
      240 ppt). As shown for the model chloromethane-producing plant Arabidopsis
      thaliana in particular, the bioreporter may provide an attractive alternative to
      analytical chemical methods to screen for natural sources of methyl halide
      emissions. 

PMID- 23956393
TI  - Use of aliphatic n-alkynes to discriminate soil nitrification activities of
      ammonia-oxidizing thaumarchaea and bacteria.
AB  - Ammonia (NH3)-oxidizing bacteria (AOB) and thaumarchaea (AOA) co-occupy most
      soils, yet no short-term growth-independent method exists to determine their
      relative contributions to nitrification in situ. Microbial monooxygenases differ
      in their vulnerability to inactivation by aliphatic n-alkynes, and we found that
      NH3 oxidation by the marine thaumarchaeon Nitrosopumilus maritimus was unaffected
      during a 24-h exposure to <= 20 MUM concentrations of 1-alkynes C8 and C9. In
      contrast, NH3 oxidation by two AOB (Nitrosomonas europaea and Nitrosospira
      multiformis) was quickly and irreversibly inactivated by 1 MUM C8 (octyne).
      Evidence that nitrification carried out by soilborne AOA was also insensitive to
      octyne was obtained. In incubations (21 or 28 days) of two different whole soils,
      both acetylene and octyne effectively prevented NH4(+)-stimulated increases in
      AOB population densities, but octyne did not prevent increases in AOA population
      densities that were prevented by acetylene. Furthermore, octyne-resistant, NH4(+)
      stimulated net nitrification rates of 2 and 7 MUg N/g soil/day persisted
      throughout the incubation of the two soils. Other evidence that octyne-resistant
      nitrification was due to AOA included (i) a positive correlation of octyne
      resistant nitrification in soil slurries of cropped and noncropped soils with
      allylthiourea-resistant activity (100 MUM) and (ii) the finding that the fraction
      of octyne-resistant nitrification in soil slurries correlated with the fraction
      of nitrification that recovered from irreversible acetylene inactivation in the
      presence of bacterial protein synthesis inhibitors and with the octyne-resistant
      fraction of NH4(+)-saturated net nitrification measured in whole soils. Octyne
      can be useful in short-term assays to discriminate AOA and AOB contributions to
      soil nitrification.

PMID- 23956394
TI  - Simultaneous near-infrared radiant heating and UV radiation for inactivating
      Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium in powdered
      red pepper (Capsicum annuum L.).
AB  - This study was conducted to investigate the efficacy of the simultaneous
      application of near-infrared (NIR) heating and UV irradiation for reducing
      populations of food-borne pathogens, including Salmonella enterica serovar
      Typhimurium and Escherichia coli O157:H7 in red pepper powder and to clarify the
      mechanisms of the lethal effect of the NIR-UV combined treatment. Also, the
      effect of the combination treatment on quality was determined by measuring
      changes in color and pungency constituents. Simultaneous NIR-UV combined
      treatment for 5 min achieved 3.34- and 2.78-log CFU reductions in S. Typhimurium
      and E. coli O157:H7, respectively, which involved 1.86- and 1.31-log CFU
      reductions, respectively, which were attributed to the synergistic effect.
      Through qualitative and quantitative analyses, damage to the cell envelope was
      identified as the main factor contributing to the synergistic lethal effect of
      NIR-UV combined treatment. Color values and capsaicin and dihydrocapsaicin
      content of NIR-UV simultaneously treated red pepper powder were not significantly
      (P > 0.05) different from those of untreated samples. These results suggest that
      simultaneous application of NIR and UV treatment can be effectively used to
      control food-borne pathogens in powdered red pepper without affecting quality. 

PMID- 23956395
TI  - Effects of inoculum additions in the presence of a preestablished arbuscular
      mycorrhizal fungal community.
AB  - Communities of arbuscular mycorrhizal fungi (AMF) are crucial for promoting plant
      productivity in most terrestrial systems, including anthropogenically managed
      ecosystems. Application of AMF inocula has therefore become a widespread
      practice. It is, however, pertinent to understand the mechanisms that govern AMF
      community composition and their performance in order to design successful
      manipulations. Here we assess whether the composition and plant growth
      promotional effects of a synthetic AMF community can be altered by inoculum
      additions of the isolates forming the community. This was determined by following
      the effects of three AMF isolates, each inoculated in two propagule densities
      into a preestablished AMF community. Fungal abundance in roots and plant growth
      were evaluated in three sequential harvests. We found a transient positive
      response in AMF abundance to the intraspecific inoculation only in the
      competitively weakest isolate. The other two isolates responded negatively to
      intra- and interspecific inoculations, and in some cases plant growth was also
      reduced. Our results suggest that increasing the AMF density may lead to
      increased competition among fungi and a trade-off with their ability to promote
      plant productivity. This is a key ecological aspect to consider when introducing
      AMF into soils. 

PMID- 23956396
TI  - Marked synergistic bactericidal effects and mode of action of medium-chain fatty
      acids in combination with organic acids against Escherichia coli O157:H7.
AB  - The aim of this study was to examine the synergistic bactericidal effects of
      medium-chain fatty acids (MCFAs; caprylic, capric, and lauric acid) and organic
      acids (OAs; acetic, lactic, malic, and citric acid) against Escherichia coli
      O157:H7 and to identify their underlying mechanism(s) of action. E. coli O157:H7
      was treated with MCFAs, OAs, or different combinations of MCFAs and OAs. Membrane
      damage and cell morphology were examined by flow cytometry and transmission
      electron microscopy, respectively. Combined treatment resulted in an additional
      log-unit reduction compared with the sum of the reductions obtained after
      individual treatment. For example, caprylic acid (1.0 mM, or 0.016%) and citric
      acid (1.0 mM, or 0.012%) alone showed negligible bactericidal effects (0.30- and
      0.06-log-unit reductions, respectively); however, a marked synergistic effect
      (>7.15-log-unit reduction) was observed when the two were combined. Although flow
      cytometry and microscopic analyses of bacteria treated with individual MCFAs and
      OAs showed evidence of membrane disruption, the bacteria were still able to form
      colonies; thus, the cell damage was recoverable. In contrast, cells exposed to
      combined treatments showed clear membrane disintegration and/or cell death
      (irreversible damage). The mechanism underlying the antimicrobial effects of
      combined treatment with MCFAs or OAs may involve disruption of the bacterial
      membrane, which then facilitates the entry of other antimicrobial compounds into
      the cytoplasm. The main advantage of combined treatment with very low
      concentrations of natural antimicrobial compounds is that it is very cost
      effective. Thus, this approach may be an alternative to more conventional
      antimicrobial treatments, such as those currently used in public health, medical
      centers, and the food industry. 

PMID- 23956397
TI  - Environmental detection of genogroup I, II, and IV noroviruses by using a generic
      real-time reverse transcription-PCR assay.
AB  - Norovirus is the most common agent implicated in food-borne outbreaks and is
      frequently detected in environmental samples. These viruses are highly diverse,
      and three genogroups (genogroup I [GI], GII, and GIV) infect humans. Being
      noncultivable viruses, real-time reverse transcription-PCR (RT-PCR) is the only
      sensitive method available for their detection in food or environmental samples.
      Selection of consensus sequences for the design of sensitive assays has been
      challenging due to sequence diversity and has led to the development of specific
      real-time RT-PCR assays for each genogroup. Thus, sample screening can require
      several replicates for amplification of each genogroup (without considering
      positive and negative controls or standard curves). This study reports the
      development of a generic assay that detects all three human norovirus genogroups
      on a qualitative basis using a one-step real-time RT-PCR assay. The generic assay
      achieved good specificity and sensitivity for all three genogroups, detected
      separately or in combination. At variance with multiplex assays, the choice of
      the same fluorescent dye for all three probes specific to each genogroup allows
      the levels of fluorescence to be added and may increase assay sensitivity when
      multiple strains from different genogroups are present. When it was applied to
      sewage sample extracts, this generic assay successfully detected norovirus in all
      samples found to be positive by the genogroup-specific RT-PCRs. The generic assay
      also identified all norovirus-positive samples among 157 archived nucleic acid
      shellfish extracts, including samples contaminated by all three genogroups. 

PMID- 23956398
TI  - Molecular analysis of the Acinetobacter baumannii biofilm-associated protein.
AB  - Acinetobacter baumannii is a multidrug-resistant pathogen associated with
      hospital outbreaks of infection across the globe, particularly in the intensive
      care unit. The ability of A. baumannii to survive in the hospital environment for
      long periods is linked to antibiotic resistance and its capacity to form
      biofilms. Here we studied the prevalence, expression, and function of the A.
      baumannii biofilm-associated protein (Bap) in 24 carbapenem-resistant A.
      baumannii ST92 strains isolated from a single institution over a 10-year period.
      The bap gene was highly prevalent, with 22/24 strains being positive for bap by
      PCR. Partial sequencing of bap was performed on the index case strain MS1968 and
      revealed it to be a large and highly repetitive gene approximately 16 kb in size.
      Phylogenetic analysis employing a 1,948-amino-acid region corresponding to the C
      terminus of Bap showed that BapMS1968 clusters with Bap sequences from clonal
      complex 2 (CC2) strains ACICU, TCDC-AB0715, and 1656-2 and is distinct from Bap
      in CC1 strains. By using overlapping PCR, the bapMS1968 gene was cloned, and its
      expression in a recombinant Escherichia coli strain resulted in increased biofilm
      formation. A Bap-specific antibody was generated, and Western blot analysis
      showed that the majority of A. baumannii strains expressed an ~200-kDa Bap
      protein. Further analysis of three Bap-positive A. baumannii strains demonstrated
      that Bap is expressed at the cell surface and is associated with biofilm
      formation. Finally, biofilm formation by these Bap-positive strains could be
      inhibited by affinity-purified Bap antibodies, demonstrating the direct
      contribution of Bap to biofilm growth by A. baumannii clinical isolates. 

PMID- 23956399
TI  - Exoproteome profiles of Clostridium cellulovorans grown on various carbon
      sources.
AB  - The cellulosome is a complex of cellulosomal proteins bound to scaffolding
      proteins. This complex is considered the most efficient system for cellulose
      degradation. Clostridium cellulovorans, which is known to produce cellulosomes,
      changes the composition of its cellulosomes depending on the growth substrates.
      However, studies have investigated only cellulosomal proteins; profile changes in
      noncellulosomal proteins have rarely been examined. In this study, we performed a
      quantitative proteome analysis of the whole exoproteome of C. cellulovorans,
      including cellulosomal and noncellulosomal proteins, to illustrate how various
      substrates are efficiently degraded. C. cellulovorans was cultured with
      cellobiose, xylan, pectin, or phosphoric acid-swollen cellulose (PASC) as the
      sole carbon source. PASC was used as a cellulose substrate for more accurate
      quantitative analysis. Using an isobaric tag method and a liquid chromatography
      mass spectrometer equipped with a long monolithic silica capillary column, 639
      proteins were identified and quantified in all 4 samples. Among these, 79
      proteins were involved in saccharification, including 35 cellulosomal and 44
      noncellulosomal proteins. We compared protein abundance by spectral count and
      found that cellulosomal proteins were more abundant than noncellulosomal
      proteins. Next, we focused on the fold change of the proteins depending on the
      growth substrates. Drastic changes were observed mainly among the noncellulosomal
      proteins. These results indicate that cellulosomal proteins were primarily
      produced to efficiently degrade any substrate and that noncellulosomal proteins
      were specifically produced to optimize the degradation of a particular substrate.
      This study highlights the importance of noncellulosomal proteins as well as
      cellulosomes for the efficient degradation of various substrates. 

PMID- 23956401
TI  - A rare presentation to TIA clinic.

PMID- 23956402
TI  - Photo quiz: A 39-year-old man with human immunodeficiency virus infection
      presenting with an alveolo-interstitial pulmonary syndrome.

PMID- 23956403
TI  - Internet-based solutions for analysis of next-generation sequence data.

PMID- 23956404
TI  - Reply to "Internet-based solutions for analysis of next-generation sequence
      data".

PMID- 23956408
TI  - From Zinnia to Arabidopsis: approaching the involvement of peroxidases in
      lignification.
AB  - Zinnia elegans constitutes one of the most useful model systems for studying
      xylem differentiation, which simultaneously involves secondary cell wall
      synthesis, cell wall lignification, and programmed cell death. Likewise, the in
      vitro culture system of Z. elegans has been the best characterized as the
      differentiation of mesophyll cells into tracheary elements allows study of the
      biochemistry and physiology of xylogenesis free from the complexity that
      heterogeneous plant tissues impose. Moreover, Z. elegans has emerged as an
      excellent plant model to study the involvement of peroxidases in cell wall
      lignification. This is due to the simplicity and duality of the lignification
      pattern shown by the stems and hypocotyls, and to the basic nature of the
      peroxidase isoenzyme. This protein is expressed not only in hypocotyls and stems
      but also in mesophyll cells transdifferentiating into tracheary elements.
      Therefore, not only does this peroxidase fulfil all the catalytic requirements to
      be involved in lignification overcoming all restrictions imposed by the
      polymerization step, but also its expression is inherent in lignification. In
      fact, its basic nature is not exceptional since basic peroxidases are
      differentially expressed during lignification in other model systems, showing
      unusual and unique biochemical properties such as oxidation of syringyl moieties.
      This review focuses on the experiments which led to a better understanding of the
      lignification process in Zinnia, starting with the basic knowledge about the
      lignin pattern in this plant, how lignification takes place, and how a sole basic
      peroxidase with unusual catalytic properties is involved and regulated by
      hormones, H2O2, and nitric oxide. 

PMID- 23956409
TI  - Biochemistry and physiological roles of enzymes that 'cut and paste' plant cell
      wall polysaccharides.
AB  - The plant cell-wall matrix is equipped with more than 20 glycosylhydrolase
      activities, including both glycosidases and glycanases (exo- and endo-hydrolases,
      respectively), which between them are in principle capable of hydrolysing most of
      the major glycosidic bonds in wall polysaccharides. Some of these enzymes also
      participate in the 'cutting and pasting' (transglycosylation) of sugar residues
      enzyme activities known as transglycosidases and transglycanases. Their action
      and biological functions differ from those of the UDP-dependent
      glycosyltransferases (polysaccharide synthases) that catalyse irreversible
      glycosyl transfer. Based on the nature of the substrates, two types of reaction
      can be distinguished: homo-transglycosylation (occurring between chemically
      similar polymers) and hetero-transglycosylation (between chemically different
      polymers). This review focuses on plant cell-wall-localized glycosylhydrolases
      and the transglycosylase activities exhibited by some of these enzymes and
      considers the physiological need for wall polysaccharide modification in vivo. It
      describes the mechanism of transglycosylase action and the classification and
      phylogenetic variation of the enzymes. It discusses the modulation of their
      expression in plants at the transcriptional and translational levels, and methods
      for their detection. It also critically evaluates the evidence that the enzyme
      proteins under consideration exhibit their predicted activity in vitro and their
      predicted action in vivo. Finally, this review suggests that wall-localized
      glycosylhydrolases with transglycosidase and transglycanase abilities are
      widespread in plants and play important roles in the mechanism and control of
      plant cell expansion, differentiation, maturation, and wall repair. 

PMID- 23956411
TI  - Molecular diversity and population structure of Chinese green foxtail [Setaria
      viridis (L.) Beauv.] revealed by microsatellite analysis.
AB  - Green foxtail (Setaria viridis) is a new model plant for the genomic
      investigation of C4 photosynthesis biology. As the ancestor of foxtail millet
      (Setaria italica), an ancient cereal of great importance in arid regions of the
      world, green foxtail is crucial for the study of domestication and evolution of
      this ancient crop. In the present study, 288 green foxtail accessions, which were
      collected from all geographical regions of China, were analysed using 77 simple
      sequence repeats (SSRs) that cover the whole genome. A high degree of molecular
      diversity was detected in these accessions, with an average of 33.5 alleles per
      locus. Two clusters, which were inconsistent with the distribution of eco
      geographical regions in China, were inferred from STRUCTURE, Neighbor-Joining,
      and principal component analysis, indicating a partially mixed distribution of
      Chinese green foxtails. The higher subpopulation diversity was from accessions
      mainly collected from North China. A low level of linkage disequilibrium was
      observed in the green foxtail genome. Furthermore, a combined analysis of green
      foxtail and foxtail millet landraces was conducted, and the origin and
      domestication of foxtail millet was inferred in North China. 

PMID- 23956410
TI  - Can prolonged exposure to low VPD disturb the ABA signalling in stomatal guard
      cells?
AB  - The response of stomata to many environmental factors is well documented.
      Multiple signalling pathways for abscisic acid (ABA)-induced stomatal closure
      have been proposed over the last decades. However, it seems that exposure of a
      leaf for a long time (several days) to some environmental conditions generates a
      sort of memory in the guard cells that results in the loss of suitable responses
      of the stomata to closing stimuli, such as desiccation and ABA. In this review
      paper we discuss changes in the normal pattern of signal transduction that could
      account for disruption of guard cell signalling after long-term exposure to some
      environmental conditions, with special emphasis on long-term low vapour pressure
      deficit (VPD). 

PMID- 23956412
TI  - Isochorismate synthase 1 is required for thylakoid organization, optimal
      plastoquinone redox status, and state transitions in Arabidopsis thaliana.
AB  - Isochorismate synthase 1 (ICS1) is a crucial enzyme in the salicylic acid (SA)
      synthesis pathway, and thus it is important for immune defences. The ics1 mutant
      is used in experiments on plant-pathogen interactions, and ICS1 is required for
      the appropriate hypersensitive disease defence response. However, ICS1 also takes
      part in the synthesis of phylloquinone, which is incorporated into photosystem I
      and is an important component of photosynthetic electron transport in plants.
      Therefore, photosynthetic and molecular analysis of the ics1 mutant in comparison
      with wild-type and SA-degrading transgenic NahG Arabidopsis thaliana plants was
      performed. Photosynthetic parameters in the ics1 mutant, when compared with the
      wild type, were changed in a manner observed previously for state transition
      impaired plants (STN7 kinase recessive mutant, stn7). In contrast to stn7,
      deregulation of the redox status of the plastoquinone pool (measured as 1-q p) in
      ics1 showed significant variation depending on the leaf age. SA-degrading
      transgenic NahG plants targeted to the cytoplasm or chloroplasts displayed normal
      (wild-type-like) state transition. However, ics1 plants treated with a
      phylloquinone precursor displayed symptoms of phenotypic reversion towards the
      wild type. ics1 also showed altered thylakoid structure with an increased number
      of stacked thylakoids per granum which indicates the role of ICS1 in regulation
      of state transition. The results presented here suggest the role of ICS1 in
      integration of the chloroplast ultrastructure, the redox status of the
      plastoquinone pool, and organization of the photosystems, which all are important
      for optimal immune defence and light acclimatory responses. 

PMID- 23956413
TI  - Piriformospora indica antagonizes cyst nematode infection and development in
      Arabidopsis roots.
AB  - The beneficial endophytic fungus Piriformospora indica colonizes the roots of
      many plant species, including the model plant Arabidopsis thaliana. Its
      colonization promotes plant growth, development, and seed production as well as
      resistance to various biotic and abiotic stresses. In the present work, P. indica
      was tested as potential antagonist of the sedentary plant-parasitic nematode
      Heterodera schachtii. This biotrophic cyst-forming nematode induces severe host
      plant damage by changing the morphogenesis and physiology of infected roots. Here
      it is shown that P. indica colonization, as well as the application of fungal
      exudates and cell-wall extracts, significantly affects the vitality, infectivity,
      development, and reproduction of H. schachtii. 

PMID- 23956415
TI  - Characterization of rhizosphere fungi that mediate resistance in tomato against
      bacterial wilt disease.
AB  - Plant immunization for resistance against a wide variety of phytopathogens is an
      effective strategy for plant disease management. Seventy-nine plant growth
      promoting fungi (PGPFs) were isolated from rhizosphere soil of India. Among them,
      nine revealed saprophytic ability, root colonization, phosphate solubilization,
      IAA production, and plant growth promotion. Seed priming with four PGPFs
      exhibited early seedling emergence and enhanced vigour of a tomato cultivar
      susceptible to the bacterial wilt pathogen compared to untreated controls. Under
      greenhouse conditions, TriH_JSB27 and PenC_JSB41 treatments remarkably enhanced
      the vegetative and reproductive growth parameters. Maximum NPK uptake was noticed
      in TriH_JSB27-treated plants. A significant disease reduction of 57.3% against
      Ralstonia solanacearum was observed in tomato plants pretreated with TriH_JSB27.
      Furthermore, induction of defence-related enzymes and genes was observed in
      plants pretreated with PGPFs or inoculated with pathogen. The maximum
      phenylalanine ammonia lyase (PAL) activity (111U) was observed at 24h in
      seedlings treated with TriH_JSB27 and this activity was slightly reduced (99U)
      after pathogen inoculation. Activities of peroxidase (POX, 54U) and beta-1,3
      glucanase (GLU, 15U) were significantly higher in control plants inoculated with
      pathogen after 24h and remained constant at all time points. A similar trend in
      gene induction for PAL was evident in PGPFs-treated tomato seedlings with or
      without pathogen inoculation, whereas POX and GLU were upregulated in control
      plus pathogen-inoculated tomato seedlings. These results determine that the
      susceptible tomato cultivar is triggered after perception of potent PGPFs to
      synthesize PAL, POX, and GLU, which activate defence resistance against bacterial
      wilt disease, thereby contributing to plant health improvement. 

PMID- 23956414
TI  - MAP65-1a positively regulates H2O2 amplification and enhances brassinosteroid
      induced antioxidant defence in maize.
AB  - Brassinosteroid (BR)-induced antioxidant defence has been shown to enhance stress
      tolerance. In this study, the role of the maize 65 kDa microtubule-associated
      protein (MAP65), ZmMAP65-1a, in BR-induced antioxidant defence was investigated.
      Treatment with BR increased the expression of ZmMAP65-1a in maize (Zea mays)
      leaves and mesophyll protoplasts. Transient expression and RNA interference
      silencing of ZmMAP65-1a in mesophyll protoplasts further revealed that ZmMAP65-1a
      is required for the BR-induced increase in expression and activity of superoxide
      dismutase (SOD) and ascorbate peroxidase (APX). Both exogenous and BR-induced
      endogenous H2O2 increased the expression of ZmMAP65-1a. Conversely, transient
      expression of ZmMAP65-1a in maize mesophyll protoplasts enhanced BR-induced H2O2
      accumulation, while transient silencing of ZmMAP65-1a blocked the BR-induced
      expression of NADPH oxidase genes and inhibited BR-induced H2O2 accumulation.
      Inhibiting the activity and gene expression of ZmMPK5 significantly prevented the
      BR-induced expression of ZmMAP65-1a. Likewise, transient expression of ZmMPK5
      enhanced BR-induced activities of the antioxidant defence enzymes SOD and APX in
      a ZmMAP65- 1a-dependent manner. ZmMPK5 directly interacted with ZmMAP65-1a in
      vivo and phosphorylated ZmMAP65-1a in vitro. These results suggest that BR
      induced antioxidant defence in maize operates through the interaction of ZmMPK5
      with ZmMAP65-1a. Furthermore, ZmMAP65-1a functions in H2O2 self-propagation via
      regulation of the expression of NADPH oxidase genes in BR signalling.

PMID- 23956416
TI  - Virus-induced gene silencing unravels multiple transcription factors involved in
      floral growth and development in Phalaenopsis orchids.
AB  - Orchidaceae, one of the largest angiosperm families, has significant commercial
      value. Isolation of genes involved in orchid floral development and
      morphogenesis, scent production, and colouration will advance knowledge of orchid
      flower formation and facilitate breeding new varieties to increase the commercial
      value. With high-throughput virus-induced gene silencing (VIGS), this study
      identified five transcription factors involved in various aspects of flower
      morphogenesis in the orchid Phalaenopsis equestris. These genes are PeMADS1,
      PeMADS7, PeHB, PebHLH, and PeZIP. Silencing PeMADS1 and PebHLH resulted in
      reduced flower size together with a pelaloid column containing petal-like
      epidermal cells and alterations of epidermal cell arrangement in lip lateral
      lobes, respectively. Silencing PeMADS7, PeHB, and PeZIP alone resulted in
      abortion of the first three fully developed flower buds of an inflorescence,
      which indicates the roles of the genes in late flower development. Furthermore,
      double silencing PeMADS1 and PeMADS6, C- and B-class MADS-box genes,
      respectively, produced a combinatorial phenotype with two genes cloned in
      separate vectors. Both PeMADS1 and PeMADS6 are required to ensure the normal
      development of the lip and column as well as the cuticle formation on the floral
      epidermal cell surface. Thus, VIGS allows for unravelling the interaction between
      two classes of MADS transcription factors for dictating orchid floral
      morphogenesis. 

PMID- 23956417
TI  - Enhancing pterin and para-aminobenzoate content is not sufficient to successfully
      biofortify potato tubers and Arabidopsis thaliana plants with folate.
AB  - Folates are important cofactors in one-carbon metabolism in all living organisms.
      Since only plants and micro- organisms are capable of biosynthesizing folates,
      humans depend entirely on their diet as a folate source. Given the low folate
      content of several staple crop products, folate deficiency affects regions all
      over the world. Folate biofortification of staple crops through enhancement of
      pterin and para-aminobenzoate levels, precursors of the folate biosynthesis
      pathway, was reported to be successful in tomato and rice. This study shows that
      the same strategy is not sufficient to enhance folate content in potato tubers
      and Arabidopsis thaliana plants and concludes that other steps in folate
      biosynthesis and/or metabolism need to be engineered to result in substantial
      folate accumulation. The findings provide a plausible explanation why, more than
      half a decade after the proof of concept in rice and tomato, successful folate
      biofortification of other food crops through enhancement of para-aminobenzoate
      and pterin content has not been reported thus far. A better understanding of the
      folate pathway is required in order to determine an engineering strategy that can
      be generalized to most staple crops. 

PMID- 23956418
TI  - Systemic lupus erythematosus immune complexes increase the expression of SLAM
      family members CD319 (CRACC) and CD229 (LY-9) on plasmacytoid dendritic cells and
      CD319 on CD56(dim) NK cells.
AB  - Patients with systemic lupus erythematosus (SLE) display an activated type I IFN
      system due to unceasing IFN-alpha release from plasmacytoid dendritic cells
      (pDCs) stimulated by nucleic acid-containing immune complexes (ICs). NK cells
      strongly promote the IFN-alpha production by pDCs; therefore, we investigated
      surface molecules that could be involved in the pDC-NK cell cross-talk. In human
      PBMCs stimulated with RNA-containing ICs (RNA-ICs), the expression of the
      signaling lymphocyte activation molecule (SLAM) family receptors CD319 and CD229
      on pDCs and CD319 on CD56(dim) NK cells was selectively increased. Upregulation
      of CD319 and CD229 on RNA-IC-stimulated pDCs was induced by NK cells or cytokines
      (e.g., GM-CSF, IL-3). IFN-alpha-producing pDCs displayed a higher expression of
      SLAM molecules compared with IFN-alpha- pDCs. With regard to signaling downstream
      of SLAM receptors, pDCs expressed SHIP-1, SHP-1, SHP-2, and CSK but lacked SLAM
      associated protein (SAP) and Ewing's sarcoma-activated transcript 2 (EAT2),
      indicating that these receptors may act as inhibitory receptors on pDCs.
      Furthermore, pDCs from patients with SLE had decreased expression of CD319 on
      pDCs and CD229 on CD56(dim) NK cells, but RNA-IC stimulation increased CD319 and
      CD229 expression. In conclusion, this study reveals that the expression of the
      SLAM receptors CD319 and CD229 is regulated on pDCs and NK cells by lupus ICs and
      that the expression of these receptors is specifically altered in SLE. These
      results, together with the observed genetic association between the SLAM locus
      and SLE, suggest a role for CD319 and CD229 in the SLE disease process.

PMID- 23956419
TI  - CD4+CD25+Foxp3+ regulatory T cells promote Th17 responses and genital tract
      inflammation upon intracellular Chlamydia muridarum infection.
AB  - The functional role of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in host
      responses to intracellular bacterial infection was investigated in an in vitro
      coculturing system and a murine model of Chlamydia muridarum genital tract
      infection. Remarkably, C. muridarum infection subverted the immune suppressive
      role of CD4+CD25+Foxp3+ Tregs; instead of hampering immune responses, Tregs not
      only promoted Th17 differentiation from conventional CD4+ T cells but also
      themselves converted into proinflammatory Th17 cells in both in vitro and in vivo
      settings. Anti-CD25 mAb PC61 treatment to deplete ~50% of pre-existing Tregs
      prior to C. muridarum genital tract infection markedly reduced the frequency and
      the total number of Th17 but not Th1 CD4+ cells at both immune induction and
      memory phases. Most importantly, Treg-depleted mice displayed significantly
      attenuated inflammation, neutrophil infiltration, and reduced severity of oviduct
      pathology upon C. muridarum genital infection. To our knowledge, this is the
      first report demonstrating that the level of pre-existing CD4+CD25+Foxp3+ Tregs
      in Chlamydia-infected hosts has a major impact on the development Chlamydia
      associated diseases.

PMID- 23956420
TI  - TLR9 deficiency promotes CD73 expression in T cells and diabetes protection in
      nonobese diabetic mice.
AB  - TLR9-deficient (TLR9-/-) NOD mice develop a significantly reduced incidence of
      diabetes. This study was to investigate the molecular mechanisms of the
      protective role of TLR9 deficiency. Through gene screening and confirmation by
      both mRNA and protein expression, we found a significant increase in CD73
      expressing immune cells from peripheral lymphoid tissues in TLR9-/- NOD mice. The
      elevated frequency of CD73-expressing immune cells seemed to be specific for TLR9
      deficiency and was MyD88 independent. Moreover, the increased frequency of CD73
      expression was limited to the NOD background. Increased frequency of CD73
      expression was also associated with lower levels of proinflammatory cytokines and
      more anti-inflammatory cytokine production in CD4+ T cells in TLR9-/- NOD mice.
      Purified CD73+CD4+ T cells showed stronger immunosuppressive function in vitro
      and delayed diabetes development in vivo. The immunosuppression appeared to be
      mediated by TGF-beta. In addition, elevated frequency of CD73-expressing cells
      was associated with improved beta cell function. Our observations were further
      confirmed by protection from diabetes with similar alterations in CD73 in the
      NY8.3 TCR NOD mouse model crossed with TLR9-/- mice and by the use of a TLR9
      inhibitor in NOD mice. Our novel findings suggest an important immune-regulatory
      role of CD73 in regulation of diabetes development and may offer a new
      therapeutic strategy for specific intervention to prevent type 1 diabetes.

PMID- 23956421
TI  - Dendritic cell reprogramming by endogenously produced lactic acid.
AB  - The demand for controlling T cell responses via dendritic cell (DC) vaccines
      initiated a quest for reliable and feasible DC modulatory strategies that would
      facilitate cytotoxicity against tumors or tolerance in autoimmunity. We studied
      endogenous mechanisms in developing monocyte-derived DCs (MoDCs) that can induce
      inflammatory or suppressor programs during differentiation, and we identified a
      powerful autocrine pathway that, in a cell concentration-dependent manner,
      strongly interferes with inflammatory DC differentiation. MoDCs developing at low
      cell culture density have superior ability to produce inflammatory cytokines, to
      induce Th1 polarization, and to migrate toward the lymphoid tissue chemokine
      CCL19. On the contrary, MoDCs originated from dense cultures produce IL-10 but no
      inflammatory cytokines upon activation. DCs from high-density cultures maintained
      more differentiation plasticity and can develop to osteoclasts. The cell
      concentration-dependent pathway was independent of peroxisome proliferator
      activated receptor gamma (PPARgamma), a known endogenous regulator of MoDC
      differentiation. Instead, it acted through lactic acid, which accumulated in
      dense cultures and induced an early and long-lasting reprogramming of MoDC
      differentiation. Our results suggest that the lactic acid-mediated inhibitory
      pathway could be efficiently manipulated in developing MoDCs to influence the
      immunogenicity of DC vaccines. 

PMID- 23956422
TI  - Resident renal mononuclear phagocytes comprise five discrete populations with
      distinct phenotypes and functions.
AB  - Recent reports have highlighted greater complexity, plasticity, and functional
      diversity of mononuclear phagocytes (MPCs), including monocytes, macrophages, and
      dendritic cells (DCs), in our organs than previously understood. The functions
      and origins of MPCs resident within healthy organs, especially in the kidney, are
      less well understood, whereas studies suggest they play roles in disease states
      distinct from recruited monocytes. We developed an unbiased approach using flow
      cytometry to analyze MPCs residing in the normal mouse kidney, and identified
      five discrete subpopulations according to CD11b/CD11c expression as well as
      F4/80, CD103, CD14, CD16, and CD64 expression. In addition to distinct marker
      profiles, these subpopulations have different lineages and expression of genes
      involved in tissue homeostasis, including angiogenesis. Among them, the
      CD11b(int)CD11c(int) F4/80(high) subpopulation notably exhibited high capacity to
      produce a representative anti-inflammatory cytokine, IL-10. Each subpopulation
      had different degrees of both macrophage (phagocytosis) and DC (Ag presentation)
      capacities, with a tendency to promote differentiation of regulatory T cells,
      whereas two of these showed expression of transcription factors reported to be
      highly expressed by classical DCs, and proclivity to exit the kidney following
      stimulation with LPS. In summary, resident kidney MPCs comprise discrete
      subpopulations, which cannot be simply classified into the conventional entities,
      and they produce anti-inflammatory and tissue-homeostatic factors to differing
      degrees.

PMID- 23956424
TI  - B cell-intrinsic and -extrinsic regulation of antibody responses by PARP14, an
      intracellular (ADP-ribosyl)transferase.
AB  - The capacity to achieve sufficient concentrations of Ag-specific Ab of the
      appropriate isotypes is a critical component of immunity that requires efficient
      differentiation and interactions of Ag-specific B and Th cells along with
      dendritic cells. Numerous bacterial toxins catalyze mono(ADP-ribosyl)ation of
      mammalian proteins to influence cell physiology and adaptive immunity. However,
      little is known about biological functions of intracellular mammalian mono(ADP
      ribosyl)transferases, such as any ability to regulate Ab responses. poly-(ADP
      ribose) polymerase 14 (PARP14), an intracellular protein highly expressed in
      lymphoid cells, binds to STAT6 and encodes a catalytic domain with mammalian
      mono(ADP-ribosyl)transferase activity. In this article, we show that recall IgA
      as well as the STAT6-dependent IgE Ab responses are impaired in PARP14-deficient
      mice. Whereas PARP14 regulation of IgE involved a B cell-intrinsic process, the
      predominant impact on IgA was B cell extrinsic. Of note, PARP14 deficiency
      reduced the levels of Th17 cells and CD103+ DCs, which are implicated in IgA
      regulation. PARP14 enhanced the expression of RORalpha, Runx1, and Smad3 after T
      cell activation, and, importantly, its catalytic activity of PARP14 promoted Th17
      differentiation. Collectively, the findings show that PARP14 influences the class
      distribution, affinity repertoire, and recall capacity of Ab responses in mice,
      as well as provide direct evidence of the requirement for protein mono-ADP
      ribosylation in Th cell differentiation.

PMID- 23956426
TI  - Human airway eosinophils exhibit preferential reduction in STAT signaling
      capacity and increased CISH expression.
AB  - Allergic asthma, a chronic respiratory disorder marked by inflammation and
      recurrent airflow obstruction, is associated with elevated levels of IL-5 family
      cytokines and elevated numbers of eosinophils (EOS). IL-5 family cytokines
      elongate peripheral blood EOS (EOS(PB)) viability, recruit EOS(PB) to the
      airways, and, at higher concentrations, induce degranulation and reactive oxygen
      species generation. Although airway EOS (EOS(A)) remain signal ready in that GM
      CSF treatment induces degranulation, treatment of EOS(A) with IL-5 family
      cytokines no longer confers a survival advantage. Because the IL-5 family
      receptors have common signaling capacity, but are uncoupled from EOS(A) survival,
      whereas other IL-5 family induced endpoints remain functional, we tested the
      hypothesis that EOS(A) possess a JAK/STAT-specific regulatory mechanism (because
      JAK/STAT signaling is critical to EOS survival). We found that IL-5 family
      induced STAT3 and STAT5 phosphorylation is attenuated in EOS(A) relative to blood
      EOS from airway allergen-challenged donors. However, IL-5 family-induced ERK1/2
      phosphorylation is not altered between EOS(A) and EOS from airway allergen
      challenged donors. These observations suggest EOS(A) possess a regulatory
      mechanism for suppressing STAT signaling distinct from ERK1/2 activation.
      Furthermore, we found, in EOS(PB), IL-5 family cytokines induce members of the
      suppressors of cytokine signaling (SOCS) genes, CISH and SOCS1. Additionally,
      following allergen challenge, EOS(A) express significantly more CISH and SOCS1
      mRNA and CISH protein than EOS(PB) counterparts. In EOS(PB), long-term
      pretreatment with IL-5 family cytokines, to varying degrees, attenuates IL-5
      family-induced STAT5 phosphorylation. These data support a model in which IL-5
      family cytokines trigger a selective downregulation mechanism in EOS(A) for
      JAK/STAT pathways.

PMID- 23956425
TI  - Global DNA methylation remodeling accompanies CD8 T cell effector function.
AB  - The differentiation of CD8 T cells in response to acute infection results in the
      acquisition of hallmark phenotypic effector functions; however, the epigenetic
      mechanisms that program this differentiation process on a genome-wide scale are
      largely unknown. In this article, we report the DNA methylomes of Ag-specific
      naive and day-8 effector CD8 T cells following acute lymphocytic choriomeningitis
      virus infection. During effector CD8 T cell differentiation, DNA methylation was
      remodeled such that changes in DNA methylation at gene promoter regions
      correlated negatively with gene expression. Importantly, differentially
      methylated regions were enriched at cis-elements, including enhancers active in
      naive T cells. Differentially methylated regions were associated with cell type
      specific transcription factor binding sites, and these transcription factors
      clustered into modules that define networks targeted by epigenetic regulation and
      control of effector CD8 T cell function. Changes in the DNA methylation profile
      following CD8 T cell activation revealed numerous cellular processes, cis
      elements, and transcription factor networks targeted by DNA methylation.
      Together, the results demonstrated that DNA methylation remodeling accompanies
      the acquisition of the CD8 T cell effector phenotype and repression of the naive
      cell state. Therefore, these data provide the framework for an epigenetic
      mechanism that is required for effector CD8 T cell differentiation and adaptive
      immune responses. 

PMID- 23956427
TI  - A synthetic TLR3 ligand mitigates profibrotic fibroblast responses by inducing
      autocrine IFN signaling.
AB  - Activation of TLR3 by exogenous microbial ligands or endogenous injury-associated
      ligands leads to production of type I IFN. Scleroderma patients with progressive
      skin fibrosis display an IFN-regulated gene signature, implicating TLR3 signaling
      in the disease. In this study, we show that TLR3 expression was detected on
      foreskin, adult skin, and lung fibroblasts, and TLR3 levels were significantly
      elevated in a subset of scleroderma skin biopsies. In explanted skin and lung
      fibroblasts, the synthetic TLR3 ligand polyinosinic-polycytidylic acid
      (poly(I:C)), a dsRNA analog, caused dose- and time-dependent stimulation of IFN
      beta production and generation of an IFN-response gene signature that was
      accompanied by substantial downregulation of collagen and alpha-smooth muscle
      actin gene expression. Furthermore, poly(I:C) abrogated TGF-beta-induced fibrotic
      responses and blocked canonical Smad signaling via upregulation of inhibitory
      Smad7. Surprisingly, the inhibitory effects of poly(I:C) in fibroblasts were
      independent of TLR3 and were mediated by the cytosolic receptors retinoic acid
      inducible gene 1 and melanoma differentiation-associated gene 5, and involved
      signaling via the IFN receptor. Taken together, these results demonstrate that
      induction of a fibroblast IFN response gene signature triggered by dsRNA is
      associated with potent TLR3-independent anti-fibrotic effects. The characteristic
      IFN response gene signature seen in scleroderma lesions might therefore signify a
      tissue-autonomous protective attempt to restrict fibroblast activation during
      injury. 

PMID- 23956429
TI  - Innate immune cell-derived microparticles facilitate hepatocarcinoma metastasis
      by transferring integrin alpha(M)beta2 to tumor cells.
AB  - Mechanisms by which tumor cells metastasize to distant organs still remain
      enigmatic. Immune cells have been assumed to be the root of metastasis by their
      fusing with tumor cells. This fusion theory, although interpreting tumor
      metastasis analogically and intriguingly, is arguable to date. We show in this
      study an alternative explanation by immune cell-derived microparticles (MPs).
      Upon stimulation by PMA or tumor cell-derived supernatants, immune cells released
      membrane-based MPs, which were taken up by H22 tumor cells, leading to tumor cell
      migration in vitro and metastasis in vivo. The underlying molecular basis was
      involved in integrin alpha(M)beta2 (CD11b/CD18), which could be effectively
      relayed from stimulated innate immune cells to MPs, then to tumor cells. Blocking
      either CD11b or CD18 led to significant decreases in MP-mediated tumor cell
      metastasis. This MP-mediated transfer of immune phenotype to tumor cells might
      also occur in vivo. These findings suggest that tumor cells may usurp innate
      immune cell phenotypes via MP pathway for their metastasis, providing new insight
      into tumor metastatic mechanism.

PMID- 23956428
TI  - CTLA4Ig inhibits effector T cells through regulatory T cells and TGF-beta.
AB  - The CD28 costimulatory receptor is a critical regulator of T cell function,
      making it an attractive therapeutic target for the treatment of immune-mediated
      diseases. CTLA4Ig, now approved for use in humans, prevents naive T cell
      activation by binding to B7 proteins and blocking engagement of CD28. However,
      CTLA4Ig suppresses inflammation even if administered when disease is established,
      suggesting alternative mechanisms. We identified a novel, CD28-independent
      mechanism by which CTLA4Ig inhibits activated T cells. We show that in vitro,
      CTLA4Ig synergizes with NO from bone marrow-derived macrophages to inhibit T cell
      proliferation. Depletion of regulatory T cells (Tregs) or interference with TGF
      beta signaling abrogated the inhibitory effect of CTLA4Ig. Parallel in vivo
      experiments using an allergic airway inflammation model demonstrated that this
      novel mechanism required both macrophages and regulatory T cells. Furthermore,
      CTLA4Ig was ineffective in SMAD3-deficient mice, supporting a requirement for TGF
      beta signaling. Thus, in addition to preventing naive T cells from being fully
      activated, CTLA4Ig can turn off already activated effector T cells by an
      NO/regulatory T cell/TGF-beta-dependent pathway. This mechanism is similar to
      cell-extrinsic effects of endogenous CTLA4 and may be particularly important in
      the ability of CTLA4Ig to treat chronic inflammatory disease. 

PMID- 23956430
TI  - Contributions of the three CYP1 monooxygenases to pro-inflammatory and
      inflammation-resolution lipid mediator pathways.
AB  - All three cytochrome P450 1 (CYP1) monooxygenases are believed to participate in
      lipid mediator biosynthesis and/or their local inactivation; however, distinct
      metabolic steps are unknown. We used multiple-reaction monitoring and liquid
      chromatography-UV coupled with tandem mass spectrometry-based lipid-mediator
      metabololipidomics to identify and quantify three lipid-mediator metabolomes in
      basal peritoneal and zymosan-stimulated inflammatory exudates, comparing
      Cyp1a1/1a2/1b1(-/-) C57BL/6J-background triple-knockout mice with C57BL/6J wild
      type mice. Significant differences between untreated triple-knockout and wild
      type mice were not found for peritoneal cell number or type or for basal CYP1
      activities involving 11 identified metabolic steps. Following zymosan-initiated
      inflammation, 18 lipid mediators were identified, including members of the
      eicosanoids and specialized proresolving mediators (i.e., resolvins and
      protectins). Compared with wild-type mice, Cyp1 triple-knockout mice exhibited
      increased neutrophil recruitment in zymosan-treated peritoneal exudates. Zymosan
      stimulation was associated with eight statistically significantly altered
      metabolic steps: increased arachidonic acid-derived leukotriene B4 (LTB4) and
      decreased 5S-hydroxyeicosatetraenoic acid; decreased docosahexaenoic acid-derived
      neuroprotectin D1/protectin D1, 17S-hydroxydocosahexaenoic acid, and 14S
      hydroxydocosahexaenoic acid; and decreased eicosapentaenoic acid-derived 18R
      hydroxyeicosapentaenoic acid (HEPE), 15S-HEPE, and 12S-HEPE. In neutrophils
      analyzed ex vivo, elevated LTB4 levels were shown to parallel increased
      neutrophil numbers, and 20-hydroxy-LTB4 formation was found to be deficient in
      Cyp1 triple-knockout mice. Together, these results demonstrate novel
      contributions of CYP1 enzymes to the local metabolite profile of lipid mediators
      that regulate neutrophilic inflammation.

PMID- 23956432
TI  - Th17 cells carrying TCR recognizing epidermal autoantigen induce psoriasis-like
      skin inflammation.
AB  - Psoriasis is considered a Th17-type autoimmune skin inflammatory disease;
      however, involvement of an autoantigen-specific TCR has not been established. In
      this study, we show that psoriasis-like skin inflammation can be induced by
      autoreactive Th17 cells. We previously developed the desmoglein 3-specific TCR
      transgenic (Dsg3H1) mouse, in which CD4+ T cells recognize physiological
      epidermal autoantigen. T cells from Dsg3H1 mice were polarized into Th17 cells in
      vitro and then adoptively transferred into Rag2-/- mice. Dsg3H1-Th17 cells
      induced severe psoriasis-like skin inflammation within 2 wk after transfer in the
      tissues in which desmoglein 3 is expressed. Such pathology was not observed when
      wild-type Th17 cells or Th1-skewed Dsg3H1 T cells were transferred, and it was
      strongly suppressed by anti-IL-12/23 and anti-IL-17 Abs. Although IFN-gamma+/IL
      17+ T cells accumulated in the skin lesions of mice that received Dsg3H1-Th17
      cells, IFN-gamma-deficient Dsg3H1-Th17 cells were fully pathogenic. These results
      demonstrate that cutaneous psoriasis-like immunopathology can be developed by
      epidermis-specific recognition of Th17 cells, which is strictly dependent on IL
      17 but not IFN-gamma.

PMID- 23956431
TI  - DNA vaccine that targets hemagglutinin to MHC class II molecules rapidly induces
      antibody-mediated protection against influenza.
AB  - New influenza A viruses with pandemic potential periodically emerge due to viral
      genomic reassortment. In the face of pandemic threats, production of conventional
      egg-based vaccines is time consuming and of limited capacity. We have developed
      in this study a novel DNA vaccine in which viral hemagglutinin (HA) is bivalently
      targeted to MHC class II (MHC II) molecules on APCs. Following DNA vaccination,
      transfected cells secreted vaccine proteins that bound MHC II on APCs and
      initiated adaptive immune responses. A single DNA immunization induced within 8 d
      protective levels of strain-specific Abs and also cross-reactive T cells. During
      the Mexican flu pandemic, a targeted DNA vaccine (HA from A/California/07/2009)
      was generated within 3 wk after the HA sequences were published online. These
      results suggest that MHC II-targeted DNA vaccines could play a role in situations
      of pandemic threats. The vaccine principle should be extendable to other
      infectious diseases. 

PMID- 23956433
TI  - Establishment of a human allergy model using human IL-3/GM-CSF-transgenic NOG
      mice.
AB  - The development of animal models that mimic human allergic responses is crucial
      to study the pathophysiology of disease and to generate new therapeutic
      methodologies. Humanized mice reconstituted with human immune systems are
      essential to study human immune reactions in vivo and are expected to be useful
      for studying human allergies. However, application of this technology to the
      study of human allergies has been limited, largely because of the poor
      development of human myeloid cells, especially granulocytes and mast cells, which
      are responsible for mediating allergic diseases, in conventional humanized mice.
      In this study, we developed a novel transgenic (Tg) strain, NOD/Shi-scid
      IL2rgamma(null) (NOG), bearing human IL-3 and GM-CSF genes (NOG IL-3/GM-Tg). In
      this strain, a large number of human myeloid cells of various lineages developed
      after transplantation of human CD34+ hematopoietic stem cells. Notably, mature
      basophils and mast cells expressing FcepsilonRI were markedly increased. These
      humanized NOG IL-3/GM-Tg mice developed passive cutaneous anaphylaxis reactions
      when administered anti-4-hydroxy-3-nitrophenylacetyl IgE Abs and 4-hydroxy-3
      nitrophenylacetyl. More importantly, a combination of serum from Japanese cedar
      pollinosis patients and cedar pollen extract also elicited strong passive
      cutaneous anaphylaxis responses in mice. Thus, to our knowledge, our NOG IL-3/GM
      Tg mice are the first humanized mouse model to enable the study of human allergic
      responses in vivo and are excellent tools for preclinical studies of allergic
      diseases.

PMID- 23956434
TI  - Characterization of resident B cells of vascular walls in human atherosclerotic
      patients.
AB  - Animal models of atherosclerosis suggest that B cells have contradictory
      protective or proatherogenic effects that are also subset and context dependent.
      To further understand the pathophysiology of human atheroma, we characterized
      local Ig production and functional properties of resident B cells in human
      arterial lesions. Ig repertoires were analyzed by RT-PCR in carotid
      endarterectomy samples. Cytokine, differentiation marker and transcription factor
      mRNA expression was studied on arterial wall lymphocytes isolated by laser
      capture microdissection. Ig sequence analysis revealed that individual samples
      each contained a limited number of B cell clones. Functional alpha and gamma
      mRNAs made up the majority of H chain mRNAs in the adventitia. Clonal evolution
      of Ig V regions, expression of activation-induced cytidine deaminase, clonal H
      chain switch, and an inverted lambda/kappa ratio of Ig L chain usage indicated
      that a local differentiation process was taking place in arterial walls.
      Clonotypic markers revealed different plaque and adventitia Ig repertoires and a
      B cell recirculation between adventitia and draining lymph nodes. Microdissected
      mononuclear cells had an activated phenotype expressing IL-6, GM-CSF, and TNF
      alpha, whereas IL-2, IL-4, IL-10, M-CSF, and IFN-gamma were not detected.
      Adventitial oligoclonal resident B cells of atherosclerotic patients are mainly
      mature B2 (conventional) CD20- plasmablasts lacking markers of terminal
      differentiation to plasma cell (CD138 and Blimp-1). They present hallmarks of Ag
      driven maturation and could act on inflammation and disease progression directly
      or by promoting polarization of other immune cells.

PMID- 23956435
TI  - Negative regulation of Nmi on virus-triggered type I IFN production by targeting
      IRF7.
AB  - Viral infection causes host cells to produce type I IFNs, which play a critical
      role in viral clearance. IFN regulatory factor (IRF) 7 is the master regulator of
      type I IFN-dependent immune responses. In this article, we report that N-Myc and
      STATs interactor (Nmi), a Sendai virus-inducible protein, interacted with IRF7
      and inhibited virus-triggered type I IFN production. The overexpression of Nmi
      inhibited the Sendai virus-triggered induction of type I IFNs, whereas the
      knockdown of Nmi promoted IFN production. Furthermore, the enhanced production of
      IFNs resulting from Nmi knockdown was sufficient to protect cells from infection
      by vesicular stomatitis virus. In addition, Nmi was found to promote the K48
      linked ubiquitination of IRF7 and the proteasome-dependent degradation of this
      protein. Finally, an impairment of antiviral responses is also detectable in Nmi
      transgenic mice. These findings suggest that Nmi is a negative regulator of the
      virus-triggered induction of type I IFNs that targets IRF7. 

PMID- 23956437
TI  - IDO1 plays an immunosuppressive role in 2,4,6-trinitrobenzene sulfate-induced
      colitis in mice.
AB  - IDO, an enzyme that degrades the essential amino acid L-tryptophan to N
      formylkynurenine, is known to exert immunomodulatory effects in a number of
      diseases and disorders. IDO expression is increased in tumors, where it is
      thought to be involved in tumor evasion by suppressing the immune response. A
      competitive inhibitor of IDO is currently being tested in clinical trials for
      relapsed or refractory solid tumors; however, there remains a concern that
      attenuation of the immunosuppressive function of IDO might exacerbate
      inflammatory responses. In this study, we investigated the role of IDO in 2,4,6
      trinitrobenzene sulfate (TNBS)-induced colitis in mice by gene deletion and
      pharmacological inhibition. TNBS treatment induced significantly more severe
      colitis in Ido1 gene-deficient (Ido1-/-) mice than in Ido1 wild-type (Ido1+/+)
      mice, indicating a role for IDO1 in suppression of acute colitis. Consistent with
      this, the expression of Ido1 was increased in the colonic interstitial tissues of
      TNBS-treated Ido1+/+ mice. Furthermore, transplantation of Ido1+/+ bone marrow
      cells into Ido1-/- mice reduced the pathological damage associated with colitis,
      altered the expression of cytokines, including IFN-gamma, TNF-alpha, and IL-10,
      and increased the number of CD4+ Foxp3+ regulatory T cells in the colon.
      Pharmacological inhibition of IDO enzymatic activity by oral administration of 1
      methyltryptophan (1-methyl-L-tryptophan or 1-methyl-D-tryptophan) significantly
      increased the severity of TNBS-induced colitis in mice, demonstrating that both
      stereoisomers can promote colitis. Collectively, our data indicate that IDO1
      plays an important immunoregulatory role in the colon.

PMID- 23956436
TI  - Persistence of the bacterial pathogen Granulibacter bethesdensis in chronic
      granulomatous disease monocytes and macrophages lacking a functional NADPH
      oxidase.
AB  - Granulibacter bethesdensis is a Gram-negative pathogen in patients with chronic
      granulomatous disease (CGD), a deficiency in the phagocyte NADPH oxidase.
      Repeated isolation of genetically identical strains from the same patient over
      years, and prolonged waxing and waning seropositivity in some subjects, raises
      the possibility of long-term persistence. G. bethesdensis resists killing by
      serum, CGD polymorphonuclear leukocytes (PMN), and antimicrobial peptides,
      indicating resistance to nonoxidative killing mechanisms. Although G.
      bethesdensis extends the survival of PMN, persistent intracellular bacterial
      survival might rely on longer-lived macrophages and their precursor monocytes.
      Therefore, we examined phagocytic killing by primary human monocytes and monocyte
      derived macrophages (MDM). Cells from both normal and CGD subjects internalized
      G. bethesdensis similarly. G. bethesdensis stimulated superoxide production in
      normal monocytes, but to a lesser degree than in normal PMN. Normal but not CGD
      monocytes and MDM killed G. bethesdensis and required in vitro treatment with IFN
      gamma to maintain this killing effect. Although in vitro IFN-gamma did not
      enhance G. bethesdensis killing in CGD monocytes, it restricted growth in
      proportion to CGD PMN residual superoxide production, providing a potential
      method to identify patients responsive to IFN-gamma therapy. In IFN-gamma-treated
      CGD MDM, G. bethesdensis persisted for the duration of the study (7 d) without
      decreasing viability of the host cells. These results indicate that G.
      bethesdensis is highly resistant to oxygen-independent microbicides of myeloid
      cells, requires an intact NADPH oxidase for clearance, and can persist long-term
      in CGD mononuclear phagocytes, most likely relating to the persistence of this
      microorganism in infected CGD patients. 

PMID- 23956438
TI  - Association of the IFNL4-DeltaG Allele With Impaired Spontaneous Clearance of
      Hepatitis C Virus.
AB  - Interferon lambda 4 protein can be generated in IFNL4-DeltaG carriers but not
      IFNL4-TT homozygotes. We studied 890 anti-hepatitis C virus (HCV)-positive
      participants in the Women's Interagency HIV Study. Among blacks (n = 555), HCV
      was more often cleared for those with genotype IFNL4-TT/TT (32.6%; odds ratio
      [OR], 3.59; P = 3.3 * 10(-5)) than IFNL4-TT/DeltaG (11.3%; OR, 0.95; P = .86) or
      IFNL4-DeltaG/DeltaG (11.9%; referent). Pooling these data with published results
      in blacks (n = 1678), ORs were 3.84 (P = 8.6 * 10(-14)) for IFNL4-TT/TT and 1.44
      (P = .03) IFNL4-TT/DeltaG, and the area under the curve was 0.64 for IFNL4-DeltaG
      genotype and 0.61 for rs12979860 (IL28B). IFNL4-DeltaG is strongly associated
      with impaired spontaneous HCV clearance. 

PMID- 23956439
TI  - High rates of incident and prevalent anal human papillomavirus infection among
      young men who have sex with men.
AB  - BACKGROUND: There are few published estimates of anal human papillomavirus (HPV)
      infection rates among young men who have sex with men (YMSM). METHODS: We
      estimated incidence and prevalence of type-specific anal HPV infection using
      clinician-collected anal swabs for HPV DNA testing obtained during a 1-year
      prospective study of 94 YMSM (mean age, 21 years) in Seattle. RESULTS: Seventy
      percent of YMSM had any HPV infection detected during the study, and HPV-16
      and/or -18 were detected in 37%. The incidence rate for any new HPV infection was
      38.5 per 1000 person-months and 15.3 per 1000 person-months for HPV-16/18; 19%
      had persistent HPV-16/18 infection. No participant tested positive for all 4 HPV
      types in the quadrivalent vaccine. The number of lifetime male receptive anal sex
      partners was significantly associated with HPV infection. The prevalence of HPV
      16/18 was 6% among YMSM with a history of 1 receptive anal sex partner and 31%
      among YMSM with >= 2 partners. CONCLUSIONS: Although the high prevalence of HPV
      among YMSM highlights the desirability of vaccinating all boys as a strategy to
      avert the morbidity of HPV infection, most YMSM appear to remain naive to either
      HPV-16 or -18 well into their sexual lives and would benefit from HPV
      immunization.

PMID- 23956440
TI  - Panton-Valentine leukocidin facilitates the escape of Staphylococcus aureus from
      human keratinocyte endosomes and induces apoptosis.
AB  - Skin and soft-tissue infections (SSTIs) caused by community-associated
      methicillin-resistant Staphylococcus aureus (CA-MRSA) have emerged as major
      health problems throughout the world. Most SSTI CA-MRSA strains produce Panton
      Valentine leukocidin (PVL), but its contribution to CA-MRSA pathogenesis is
      poorly defined. Here, we used an endemic PVL-positive SSTI-causing CA-MRSA strain
      from Taiwan, together with an isogenic PVL-knockout mutant (Deltapvl) and
      complemented PVL-positive derivative, to evaluate the role of PVL in the
      pathogenesis of CA-MRSA in the RHEK-1 human keratinocyte cell line and a rabbit
      skin infection model. We found that both PVL-positive CA-MRSA and isogenic
      Deltapvl strains attached and were engulfed into endosomes of RHEK-1 cells within
      1 hour following infection. However, by 2 hours after infection PVL-positive CA
      MRSA more effectively disrupted endosomes, escaped into the cytoplasm, and
      replicated intracellularly. By 6 hours after infection, the PVL-positive strain
      caused significantly more caspase-dependent keratinocyte apoptosis than the
      isogenic Deltapvl mutant. In the rabbit infection model, 1 week following
      infection the wild-type strain produced significantly more widespread lesions and
      cell apoptosis than the isogenic Deltapvl mutant. These findings indicate that
      PVL is an important virulence factor that enables CA-MRSA to produce necrotizing
      skin infections by allowing the bacteria to escape from endosomes, replicate
      intracellularly, and induce apoptosis. 

PMID- 23956441
TI  - The effect of decreased-dose idarubicin for elderly patients with acute myeloid
      leukemia.
AB  - We evaluated whether reduced-dose chemotherapy with 2 days of idarubicin (12
      mg/m(2)) and 5 days of cytarabine (100 mg/m(2)) (2 + 5) is effective for patients
      aged 65-74 by retrospectively comparing the results with those aged 55-64 treated
      with 3 + 7. In 1999-2009, we treated 20 patients aged 65-74 with 2 + 5, and 23
      patients aged 55-64 with 3 + 7. The complete remission rates by the first
      induction were 50.0 and 69.6% for older and younger groups (P = 0.203). Two-year
      overall survival rates were 55.9 and 32.3% for older and younger groups; 2-year
      rates of relapse-free survival for all these patients were 15.7 and 36.5%. The
      differences in overall and relapse-free survival were statistically insignificant
      (P = 0.726 and 0.413, respectively). The treatment results of 2 + 5 for the older
      group were not significantly worse compared with those of 3 + 7 for the younger.
      Therefore, elderly patients who do not tolerate 3 + 7 should still benefit from 2
      + 5. 

PMID- 23956442
TI  - Hand-foot skin reaction is associated with the clinical outcome in patients with
      metastatic renal cell carcinoma treated with sorafenib.
AB  - BACKGROUND: To elucidate whether Hand-Foot skin reaction could become a biomarker
      of clinical outcome in patients with metastatic renal cell carcinoma treated with
      sorafenib, we retrospectively examined the association between the Hand-Foot skin
      reaction and the clinical outcome in metastatic renal cell carcinoma patients
      treated with sorafenib. METHODS: Thirty-six Japanese metastatic renal cell
      carcinoma patients treated with sorafenib were enrolled and divided into the
      groups with or without Hand-Foot skin reaction. Patient characteristics, best
      tumor response, progression-free survival and adverse events were investigated
      and compared between these two groups. RESULTS: A sorafenib-induced Hand-Foot
      skin reaction in metastatic renal cell carcinoma patients was observed at a
      significantly higher rate in patients in the favorable-risk group in the Memorial
      Sloan-Kettering Cancer Center risk classification, and with Eastern Cooperative
      Oncology Group Performance Status of one or less, prior nephrectomy, higher
      hemoglobin, lower lactate dehydrogenase and lower C-reactive protein. The mean
      best tumor response was significantly better in the group with Hand-Foot skin
      reaction (-16.7%) than that in the group without it (17.9%; P < 0.001). The
      median progression-free survival was significantly longer in the group with Hand
      Foot skin reaction (4.6 months) than that in the group without it (1.5 months; P
      = 0.002). In multivariate analysis, only Hand-Foot skin reaction was shown to be
      a predictive factor of progression-free survival (hazard ratio 0.312, P = 0.010).
      CONCLUSIONS: A sorafenib-induced Hand-Foot skin reaction in metastatic renal cell
      carcinoma patients emerged at a significantly higher rate in patients in the
      favorable-risk group in the Memorial Sloan-Kettering Cancer Center risk
      classification and was significantly associated with best tumor response and
      progression-free survival, suggesting that Hand-Foot skin reaction might be an
      independent predictive factor for clinical outcome in metastatic renal cell
      carcinoma patients treated with sorafenib.

PMID- 23956443
TI  - Role of HDL in cholesteryl ester metabolism of lipopolysaccharide-activated
      P388D1 macrophages.
AB  - Infections share with atherosclerosis similar lipid alterations, with
      accumulation of cholesteryl esters (CEs) in activated macrophages and concomitant
      decrease of cholesterol-HDL (C-HDL). Yet the precise role of HDL during microbial
      infection has not been fully elucidated. Activation of P388D1 by
      lipopolysaccharide (LPS) triggered an increase of CEs and neutral lipid contents,
      along with a remarkable enhancement in 1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate-HDL uptake. Similar results were found in
      human monocyte-derived macrophages and monocytes cocultured with
      phytohemagglutinin-activated lymphocytes. Inhibition of cholesterol
      esterification with Sandoz-58035 resulted in 80% suppression of CE biosynthesis
      in P388D1. However, only a 35% decrease of CE content, together with increased
      scavenger receptor class B member 1 (SR-B1) protein expression, was found after
      72 h and thereafter up to 16 passages of continuous ACAT suppression. Chronic
      inhibition blunted the effect of LPS treatment on cholesterol metabolism,
      increased the ratio of free cholesterol/CE content and enhanced interleukin 6
      secretion. These results imply that, besides de novo biosynthesis and acquisition
      by LDL, HDL contributes probably through SR-B1 to the increased CE content in
      macrophages, partly explaining the low levels of C-HDL during their activation.
      Our data suggest that in those conditions where more CEs are required, HDL rather
      than removing, may supply CEs to the cells.

PMID- 23956444
TI  - Inhibition of myeloperoxidase decreases vascular oxidative stress and increases
      vasodilatation in sickle cell disease mice.
AB  - Activated leukocytes and polymorphonuclear neutrophils (PMN) release
      myeloperoxidase (MPO), which binds to endothelial cells (EC), is translocated,
      and generates oxidants that scavenge nitric oxide (NO) and impair EC function. To
      determine whether MPO impairs EC function in sickle cell disease (SCD), control
      (AA) and SCD mice were treated with N-acetyl-lysyltyrosylcysteine-amide (KYC).
      SCD humans and mice have high plasma MPO and soluble L-selectin (sL-selectin).
      KYC had no effect on MPO but decreased plasma sL-selectin and malondialdehyde in
      SCD mice. MPO and 3-chlorotyrosine (3-ClTyr) were increased in SCD aortas. KYC
      decreased MPO and 3-ClTyr in SCD aortas to the levels in AA aortas.
      Vasodilatation in SCD mice was impaired. KYC increased vasodilatation in SCD mice
      more than 2-fold, to ~60% of levels in AA mice. KYC inhibited MPO-dependent 3
      ClTyr formation in EC proteins. SCD mice had high plasma alanine transaminase
      (ALT), which tended to decrease in KYC-treated SCD mice (P = 0.07). KYC increased
      MPO and XO/XDH and decreased 3-ClTyr and 3-nitrotyrosine (3-NO2Tyr) in SCD
      livers. These data support the hypothesis that SCD increases release of MPO,
      which generates oxidants that impair EC function and injure livers. Inhibiting
      MPO is an effective strategy for decreasing oxidative stress and liver injury and
      restoring EC function in SCD.

PMID- 23956446
TI  - Criteria and prediction models for mismatch repair gene mutations: a review.
AB  - One of the strongest predictors of colorectal cancer risk is carrying a germline
      mutation in a DNA mismatch repair (MMR) gene. Once identified, mutation carriers
      can be recommended for intensive screening that will substantially reduce their
      high colorectal cancer risk. Conversely, the relatives of carriers identified as
      non-carriers can be relieved of the burden of intensive screening. Criteria and
      prediction models that identify likely mutation carriers are needed for cost
      effective, targeted, germline testing for MMR gene mutation. We reviewed 12
      criteria/guidelines and 8 prediction models (Leiden, Amsterdam-plus, Amsterdam
      alternative, MMRpro, PREMM1,2,6, MMRpredict, Associazione Italiana per lo studio
      della Familiarita ed Ereditarieta dei tumori Gastrointestinali (AIFEG) and the
      Myriad Genetics Prevalence table) for identifying mutation carriers. While
      criteria are only used to identify individuals with colorectal cancer (yes/no for
      screening followed by germline testing), all prediction models except MMRpredict
      and Myriad tables can predict the probability of carrying mutations for
      individuals with or without colorectal cancer. We conducted a meta-analysis of
      the discrimination performance of 17 studies that validated the prediction
      models. The pooled estimate for the area under curve was 0.80 (95% CI 0.72 to
      0.88) for MMRpro, 0.81 (95% CI 0.73 to 0.88) for MMRpredict, 0.84 (95% CI 0.81 to
      0.88) for PREMM, and 0.85 (95% CI 0.78 to 0.91) for Leiden model. Given the high
      degree of overlap in the CIs, we cannot state that one model has a higher
      discrimination than any of the others. Overall, the existing statistical models
      have been shown to be sensitive and specific (at a 5% cut-off) in predicting MMR
      gene mutation carriers. Future models may need to: provide prediction of PMS2
      mutations, take into account a wider range of Lynch syndrome-associated cancers
      when assessing family history, and be applicable to all people irrespective of
      any cancer diagnosis. 

PMID- 23956452
TI  - Researchers link early hair loss and prostate cancer.

PMID- 23956445
TI  - 10E,12Z-conjugated linoleic acid impairs adipocyte triglyceride storage by
      enhancing fatty acid oxidation, lipolysis, and mitochondrial reactive oxygen
      species.
AB  - Conjugated linoleic acid (CLA) is a naturally occurring dietary trans fatty acid
      found in food from ruminant sources. One specific CLA isomer, 10E,12Z-CLA, has
      been associated with health benefits, such as reduced adiposity, while
      simultaneously promoting deleterious effects, such as systemic inflammation,
      insulin resistance, and dyslipidemia. The precise mechanisms by which 10E,12Z-CLA
      exerts these effects remain unknown. Despite potential health consequences, CLA
      continues to be advertised as a natural weight loss supplement, warranting
      further studies on its effects on lipid metabolism. We hypothesized that 10E,12Z
      CLA impairs lipid storage in adipose tissue by altering the lipid metabolism of
      white adipocytes. We demonstrate that 10E,12Z-CLA reduced triglyceride storage
      due to enhanced fatty acid oxidation and lipolysis, coupled with diminished
      glucose uptake and utilization in cultured adipocytes. This switch to lipid
      utilization was accompanied by a potent proinflammatory response, including the
      generation of cytokines, monocyte chemotactic factors, and mitochondrial
      superoxide. Disrupting fatty acid oxidation restored glucose utilization and
      attenuated the inflammatory response to 10E,12Z-CLA, suggesting that fatty acid
      oxidation is critical in promoting this phenotype. With further investigation
      into the biochemical pathways involved in adipocyte responses to 10E,12Z-CLA, we
      can discern more information about its safety and efficacy in promoting weight
      loss. 

PMID- 23956454
TI  - Advanced breast cancer in young women.

PMID- 23956456
TI  - Saccadic and smooth-pursuit eye movements during reading of drifting texts.
AB  - Reading is a complex visuomotor behavior characterized by an alternation of
      fixations and saccadic eye movements. Despite the widespread use of drifting
      texts in various settings, very little is known about eye movements under these
      conditions. Here we investigated oculomotor behavior during reading of texts
      which were drifting horizontally or vertically at different speeds. Consistent
      with previous reports, drifting texts were read by an alternation of smooth
      pursuit and saccadic eye movements. Detailed analysis revealed several
      interactions between smooth pursuit and saccades. On one side, the gain of smooth
      pursuit was increased after the execution of a saccade. On the other side, the
      peak velocity of saccades was reduced for the horizontally drifting text, in
      which saccades and pursuit were executed in opposite directions. In addition, we
      show that well-known findings from the reading of static texts extend to drifting
      text, such as the preferred viewing location, the inverted optimal viewing
      position, and the correlation between saccade amplitude and subsequent
      pursuit/fixation duration. In general, individual eye-movement parameters such as
      saccade amplitude and fixation/pursuit durations were correlated across self
      paced reading of static text and time-constrained reading of static and drifting
      texts. These results show that findings from basic oculomotor research also apply
      to the reading of drifting texts. Similarly, basic reading principles apply to
      the reading of static and drifting texts in a similar way. This exemplifies the
      reading of drifting text as a visuomotor behavior which is influenced by low
      level eye-movement control as well as by cognitive and linguistic processing. 

PMID- 23956458
TI  - A semiparametric additive rate model for recurrent events with an informative
      terminal event.
AB  - We propose a semiparametric additive rate model for modelling recurrent events in
      the presence of a terminal event. The dependence between recurrent events and
      terminal event is nonparametric. A general transformation model is used to model
      the terminal event. We construct an estimating equation for parameter estimation
      and derive the asymptotic distributions of the proposed estimators. Simulation
      studies demonstrate that the proposed inference procedure performs well in
      realistic settings. Application to a medical study is presented.

PMID- 23956457
TI  - Predicted and observed mortality from vector-borne disease in small songbirds.
AB  - Numerous diseases of wildlife have recently emerged due to trade and travel.
      However, the impact of disease on wild animal populations has been notoriously
      difficult to detect and demonstrate, due to problems of attribution and the rapid
      disappearance of bodies after death. Determining the magnitude of avian mortality
      from West Nile virus (WNV) is emblematic of these challenges. Although
      correlational analyses may show population declines coincident with the arrival
      of the virus, strong inference of WNV as a cause of mortality or a population
      decline requires additional evidence. We show how integrating field data on
      mosquito feeding patterns, avian abundance, and seroprevalence can be used to
      predict relative mortality from vector-borne pathogens. We illustrate the method
      with a case study on WNV in three species of small songbirds, tufted titmouse
      (Baeolophus bicolor), Carolina wrens (Thryothorus ludovicianus), and northern
      cardinals (Cardinalis cardinalis). We then determined mortality, infectiousness,
      and behavioral response of wrens and titmouse following infection with WNV in
      laboratory experiments and compared them to a previous study on WNV mortality in
      cardinals. In agreement with predictions, we found titmouse had the highest
      mortality from WNV infection, with 100% of eleven birds perishing within seven
      days after infection. Mortality in wrens was significantly lower at 27% (3/11),
      but still substantial. Viremia profiles indicated that both species were highly
      infectious for WNV and could play roles in WNV amplification. These findings
      suggest that WNV may be killing many small-bodied birds, despite the absence of
      large numbers of dead birds testing positive for WNV. More broadly, they
      illustrate a framework for predicting relative mortality in hosts from vector
      borne disease.

PMID- 23956459
TI  - Attributable fraction functions for censored event times.
AB  - Attributable fractions are commonly used to measure the impact of risk factors on
      disease incidence in the population. These static measures can be extended to
      functions of time when the time to disease occurrence or event time is of
      interest. The present paper deals with nonparametric and semiparametric
      estimation of attributable fraction functions for cohort studies with potentially
      censored event time data. The semiparametric models include the familiar
      proportional hazards model and a broad class of transformation models. The
      proposed estimators are shown to be consistent, asymptotically normal and
      asymptotically efficient. Extensive simulation studies demonstrate that the
      proposed methods perform well in practical situations. A cardiovascular health
      study is provided. Connections to causal inference are discussed.

PMID- 23956460
TI  - The multivariate beta process and an extension of the Polya tree model.
AB  - We introduce a novel stochastic process that we term the multivariate beta
      process. The process is defined for modelling-dependent random probabilities and
      has beta marginal distributions. We use this process to define a probability
      model for a family of unknown distributions indexed by covariates. The marginal
      model for each distribution is a Polya tree prior. An important feature of the
      proposed prior is the easy centring of the nonparametric model around any
      parametric regression model. We use the model to implement nonparametric
      inference for survival distributions. The nonparametric model that we introduce
      can be adopted to extend the support of prior distributions for parametric
      regression models.

PMID- 23956461
TI  - Bayesian geostatistical modelling with informative sampling locations.
AB  - We consider geostatistical models that allow the locations at which data are
      collected to be informative about the outcomes. A Bayesian approach is proposed,
      which models the locations using a log Gaussian Cox process, while modelling the
      outcomes conditionally on the locations as Gaussian with a Gaussian process
      spatial random effect and adjustment for the location intensity process. We prove
      posterior propriety under an improper prior on the parameter controlling the
      degree of informative sampling, demonstrating that the data are informative. In
      addition, we show that the density of the locations and mean function of the
      outcome process can be estimated consistently under mild assumptions. The methods
      show significant evidence of informative sampling when applied to ozone data over
      Eastern U.S.A.

PMID- 23956462
TI  - Gender Dynamics Predict Changes in Marital Love Among African American Couples.
AB  - This study examined the implications of gender attitudes and spouses' divisions
      of household labor, time with children, and parental knowledge for their
      trajectories of love in a sample of 146 African American couples. Multilevel
      modeling in the context of an accelerated longitudinal design accommodated 3
      annual waves of data. The results revealed that traditionality in husbands'
      gender attitudes was linked to lower levels of love. Furthermore, divisions of
      household labor and parental knowledge moderated changes in love such that
      couples with more egalitarian divisions exhibited higher and more stable patterns
      of love, whereas more traditional couples exhibited significant declines in love
      over time. Finally, greater similarity between spouses' time with their children
      was linked to higher levels of marital love. The authors highlight the
      implications of gender dynamics for marital harmony among African American
      couples and discuss ways that this work may be applied and extended in practice
      and future research.

PMID- 23956463
TI  - Resilin-Based Hybrid Hydrogels for Cardiovascular Tissue Engineering.
AB  - The outstanding elastomeric properties of natural resilin, an insect protein,
      have motivated the engineering of resilin-like polypeptides (RLPs) as a potential
      material for cardiovascular tissue engineering. The RLPs, which incorporate
      biofunctional domains for cell-matrix interactions, are cross-linked into RLP-PEG
      hybrid hydrogels via a Michael-type addition of cysteine residues on the RLP with
      vinyl sulfones of an end-functionalized multi-arm star PEG. Oscillatory rheology
      indicated the useful mechanical properties of these materials. Assessments of
      cell viability via con-focal microscopy clearly show the successful encapsulation
      of human aortic adventitial fibroblasts in the three-dimensional matrices and the
      adoption of a spread morphology following 7 days of culture.

PMID- 23956464
TI  - Bright Light Emission and Waveguiding in Conjugated Polymer Nanofibers
      Electrospun from Organic Salt Added Solutions.
AB  - Light-emitting electrospun nanofibers of poly[(9,9-dioctylfluorenyl-2,7-diyl)-co
      ( N,N '-diphenyl)- N,N '-di(p-butyl-oxy-phenyl)-1,4-diaminobenzene)] (PFO-PBAB)
      are produced by electrospinning under different experimental conditions. In
      particular, uniform fibers with average diameter of 180 nm are obtained by adding
      an organic salt to the electrospinning solution. The spectroscopic investigation
      assesses that the presence of the organic salt does not alter the optical
      properties of the active material, therefore providing an alternative approach
      for the fabrication of highly emissive conjugated polymer nanofibers. The
      produced nanofibers display self-waveguiding of light, and polarized
      photoluminescence, which is especially promising for embedding active electrospun
      fibers in sensing and nanophotonic devices.

PMID- 23956465
TI  - Analyzing Screening Policies for Childhood Obesity.
AB  - Due to the health and economic costs of childhood obesity, coupled with studies
      suggesting the benefits of comprehensive (dietary, physical activity and
      behavioral counseling) intervention, the United States Preventive Services Task
      Force recently recommended childhood screening and intervention for obesity
      beginning at age six. Using a longitudinal data set consisting of the body mass
      index of 3164 children up to age 18 and another longitudinal data set containing
      the body mass index at ages 18 and 40 and the presence or absence of disease
      (hypertension and diabetes) at age 40 for 747 people, we formulate and
      numerically solve - separately for boys and girls - a dynamic programming problem
      for the optimal biennial (i.e., at ages 2, 4, ..., 16) obesity screening
      thresholds. Unlike most screening problem formulations, we take a societal
      viewpoint, where the state of the system at each age is the population-wide
      probability density function of the body mass index. Compared to the biennial
      version of the task force's recommendation, the screening thresholds derived from
      the dynamic program achieve a relative reduction in disease prevalence of 3% at
      the same screening (and treatment) cost, or - due to the flatness of the disease
      vs. screening tradeoff curve - achieves the same disease prevalence at a 28%
      relative reduction in cost. Compared to the task force's policy, which uses the
      95th percentile of body mass index (from cross-sectional growth charts tabulated
      by the Centers for Disease Control and Prevention) as the screening threshold for
      each age, the dynamic programming policy treats mostly 16 year olds (including
      many who are not obese) and very few males under 14 years old. While our results
      suggest that adult hypertension and diabetes are minimized by focusing childhood
      obesity screening and treatment on older adolescents, the shortcomings in the
      available data and the narrowness of the medical outcomes considered prevent us
      from making a recommendation about childhood obesity screening policies.

PMID- 23956466
TI  - Telomere dynamics in mice and humans.
AB  - Telomeres are ribonucleoprotein structures capping the end of every linear
      chromosome. In all vertebrates, they are composed of TTAGGG repeats coated with
      specific protecting proteins. Telomeres shorten with each mitotic cell division,
      but telomerase, a reverse transcriptase, elongate telomeres in very specific
      cells, such as embryonic and adult stem cells. Although telomere sequence is
      identical in mice and humans and telomeres serve the same role of protecting
      chromosomes and genetic information from damage and erosion in both species,
      abnormalities in telomere maintenance and in telomerase function do not coincide
      in phenotype in humans and mice. The telomeres of most laboratory mice are 5 to
      10 times longer than in humans, but their lifespan is 30 times shorter. Complete
      absence of telomerase has little expression in phenotype over several generations
      in mice, whereas heterozygosity for telomerase mutations in humans is sufficient
      to result in organ regeneration defect and cancer development. Patients with
      telomerase deficiency and very short telomeres may develop aplastic anemia,
      pulmonary fibrosis, or cirrhosis, whereas telomerase-null murine models display
      only modest hematopoietic deficiency and develop emphysema when exposed to
      cigarette smoke. In summary, telomerase deficiency in both humans and mice
      accelerate telomere shortening, but its consequences in the different organs and
      in the organism diverge, mainly due to telomere length differences.

PMID- 23956468
TI  - Total synthesis of zyzzyanones A-D.
AB  - Zyzzyanones A-D is a group of biologically active marine alkaloids isolated from
      Australian marine sponge Zyzzya fuliginosa. They contain a unique
      bispyrroloquinone ring system as the core structure. The first total synthesis of
      all four zyzzyanones is described here. The synthesis of these alkaloids started
      from a previously known 6-benzylamino indole-4,7-quinone derivative and involves
      6-7 steps. The key step in the synthesis involves the construction of a pyrrole
      ring in one step using a Mn(OAc)3 mediated oxidative free radical cyclization
      reaction of a 6-benzylamino indole-4,7-quinone derivative with 4-benzyloxyphenyl
      acetaldehyde diethyl acetal in CH3CN.

PMID- 23956467
TI  - Animal models of hemophilia and related bleeding disorders.
AB  - Animal models of hemophilia and related diseases are important for the
      development of novel treatments and to understand the pathophysiology of bleeding
      disorders in humans. Testing in animals with the equivalent human disorder
      provides informed estimates of doses and measures of efficacy, which aids in
      design of human trials. Many models of hemophilia A, hemophilia B, and von
      Willebrand disease (VWD) have been developed from animals with spontaneous
      mutations (hemophilia A dogs, rats, sheep; hemophilia B dogs; and VWD pigs and
      dogs), or by targeted gene disruption in mice to create hemophilia A, B, or VWD
      models. Animal models have been used to generate new insights into the
      pathophysiology of each bleeding disorder and also to perform preclinical
      assessments of standard protein replacement therapies, as well as novel gene
      transfer technology. The differences both between species and in underlying
      causative mutations must be considered in choosing the best animal for a specific
      scientific study.

PMID- 23956469
TI  - Temperature-dependent, competitive 1,3-acyl shift versus decarbonylation of a
      cyclopropanone intermediate.
AB  - Photooxygenation of 1,1,3-trimethyl-1,2-dihydropentalene gives an unstable
      endoperoxide which upon decomposition delivers a bicyclic cyclopropanone
      intermediate; this species either extrudes CO to give a cycloheptadienone or
      undergoes a 1,3-acyl shift, both processes occurring most likely in a stepwise
      manner via diradical intermediates. Alternatively, C3a-C4 cleavage in the
      dioxygen diradical derived from the endoperoxide yields a 2-cyclopropyl
      substituted cyclopentadienone epoxide.

PMID- 23956470
TI  - Asymmetric transition metal-catalyzed cross-coupling reactions for the
      construction of tertiary stereocenters.

PMID- 23956472
TI  - Waol A, trans-dihydrowaol A, and cis-dihydrowaol A: polyketide-derived gamma
      lactones from a Volutella species.
AB  - An organic extract of a filamentous fungus (MSX 58801), identified as a Volutella
      sp. (Hypocreales, Ascomycota), displayed moderate cytotoxic activity against NCI
      H460 human large cell lung carcinoma. Bioactivity-directed fractionation led to
      the isolation of three gamma-lactones having the furo[3,4-b]pyran-5-one bicyclic
      ring system [waol A (1), trans-dihydrowaol A (2), and cis-dihydrowaol A (3)]. The
      structures were elucidated using a set of spectroscopic and spectrometric
      techniques; the absolute configuration of 2 was established via a modified
      Mosher's ester method. Compounds 1 and 2 were evaluated for cytotoxicity against
      a human cancer cell panel.

PMID- 23956473
TI  - A Pretreatment Method for Analysing Albendazole by HPLC in Plant Material.
AB  - Albendazole (ALB) belongs to a group of benzimidazoles-classified as
      antiparasitic pharmaceuticals. Its widespread application results in the presence
      of this pharmaceutical in natural environment (water and soil). In this paper a
      suitable pretreatment method was established including sampling, freeze-drying
      and extraction. Vicia faba was used as model organism. ALB accumulation by plant
      tissues was observed in hydroponic culture as well as in soil. The range of
      pharmaceutical concentrations was 1.7 * 10-5 mol/L (in hydroponic culture) and
      1.7 * 10-5 to 1.7 * 10-4 mol/kg air dry soil (in soil). Observations were
      conducted for 14 days. After this time biological material was freeze-dried and
      after homogenization, dimethyl sulfoxide (DMSO) extraction was performed. The
      recovery of ALB for the roots was 93 % while for the shoots 86 %. After cleaning,
      the samples were subjected to further analysis by HPLC system. Phosphate buffer
      and acetonitrile (50:50) were used as a mobile phase. Drug retention time was 6.3
      min. Results obtained in this experiment indicate higher drug accumulation in
      roots rather than in the hypocotyl part of the plant, cultivated both in soil and
      in hydroponic culture.

PMID- 23956471
TI  - Toward the Ideal Synthesis and Transformative Therapies: The Roles of Step
      Economy and Function Oriented Synthesis.

PMID- 23956475
TI  - Evaluation of MODIS surrogates for meteorological humidity data in east Africa.
AB  - Satellite remote sensing technology has shown promising results in characterizing
      the environment in which plants and animals thrive. Remote sensing scientists,
      biologists, and epidemiologists are adopting remotely sensed imagery to
      compensate for the paucity of weather information measured by weather stations.
      With measured humidity from three stations as baselines, our study reveals that
      Normalised Difference Vegetation Index (NDVI) and atmosphere saturation deficits
      at the 780 hPa pressure level (DMODIS), both of which were derived from the
      MODerate-resolution Imaging Spectroradiometer (MODIS) sensor, were significantly
      correlated with station saturation deficits (Dstn)(ourou = 0.42-0.63, p < 0.001).
      These metrics have the potential to estimate saturation deficits over east
      Africa. Four to nine days of lags were found in the NDVI responding to Dstn. For
      the daily estimations of Dstn, DMODIS had a better performance than the NDVI.
      However, both of them poorly explained the variances in daily Dstn using simple
      regression models (adj. R2 = 0.17-0.39). When the estimation temporal scale was
      changed to 16-day, their performances were similar, and both were better than
      daily estimations. For Dstn estimations at coarser geographic scales, given that
      many factors such as soil, vegetation, slope, aspect, and wind speed might
      complicate the NDVI response lags and model construction, DMODIS is more
      favourable as a proxy of the saturation deficit over ground due to its simple
      relationship with Dstn.

PMID- 23956474
TI  - The General Factor of Personality: A General Critique.
AB  - Recently, it has been proposed that all non-cognitive measures of personality
      share a general factor of personality. A problem with many of these studies is a
      lack of clarity in defining a general factor. In this paper we address the
      multiple ways in which a general factor has been identified and argue that many
      of these approaches find factors that are not in fact general. Through the use of
      artificial examples, we show that a general factor is not: The first factor or
      component of a correlation or covariance matrix.The first factor resulting from a
      bifactor rotation or biquartimin transformationNecessarily the result of a
      confirmatory factor analysis forcing a bifactor solution We consider how the
      definition of what constitutes a general factor can lead to confusion, and we
      will demonstrate alternative ways of estimating the general factor saturation
      that are more appropriate.

PMID- 23956476
TI  - FORECASTING WITH PREDICTION INTERVALS FOR PERIODIC ARMA MODELS.
AB  - Periodic autoregressive moving average (PARMA) models are indicated for time
      series whose mean, variance, and covariance function vary with the season. In
      this paper, we develop and implement forecasting procedures for PARMA models.
      Forecasts are developed using the innovations algorithm, along with an idea of
      Ansley. A formula for the asymptotic error variance is provided, so that Gaussian
      prediction intervals can be computed. Finally, an application to monthly river
      flow forecasting is given, to illustrate the method.

PMID- 23956477
TI  - Do Adults Adjust their Socioeconomic Status Identity in Later Life?*
AB  - Previous research shows that socioeconomic status (SES) identity, also referred
      to as perceived or subjective social status, is shaped by objective measures of
      status, socio-cultural influences and psychological attributes and predicts
      current and future well-being. Prior studies, however, have not examined whether
      older adults reassess their SES identity over time. In this study, we use two
      assessments of subjective social status measured six years apart in a sample of
      older Taiwanese adults to: 1) determine the degree to which respondents adjust
      their perceptions of social rank; and 2) identify the characteristics of
      individuals who are most likely to revise their assessments. We find that many
      older Taiwanese adults reassess their SES identity, but most respondents show
      small to moderate levels of change. Females, more highly educated respondents,
      and those who have a positive economic outlook tend to revise their subjective
      social status upward relative to their respective counterparts; those who become
      widowed during the period adjust their rankings downward compared with those who
      do not become widowed. These findings suggest that SES identity may be dynamic,
      highlighting the importance of collecting information on socioeconomic status
      identity at multiple points in the life course.

PMID- 23956478
TI  - Objective speech intelligibility measurement for cochlear implant users in
      complex listening environments.
AB  - Objective intelligibility measurement allows for reliable, low-cost, and
      repeatable assessment of innovative speech processing technologies, thus
      dispensing costly and time-consuming subjective tests. To date, existing
      objective measures have focused on normal hearing model, and limited use has been
      found for restorative hearing instruments such as cochlear implants (CIs). In
      this paper, we have evaluated the performance of five existing objective
      measures, as well as proposed two refinements to one particular measure to better
      emulate CI hearing, under complex listening conditions involving noise-only,
      reverberation-only, and noise-plus-reverberation. Performance is assessed against
      subjectively rated data. Experimental results show that the proposed CI-inspired
      objective measures outperformed all existing measures; gains by as much as 22%
      could be achieved in rank correlation.

PMID- 23956479
TI  - Photon Parameterisation for Robust Relaxation Constraints.
AB  - This paper presents a novel approach to detecting and preserving fine
      illumination structure within photon maps. Data derived from each photon's primal
      trajectory is encoded and used to build a high-dimensional kd-tree. Incorporation
      of these new parameters allows for precise differentiation between intersecting
      ray envelopes, thus minimizing detail degradation when combined with photon
      relaxation. We demonstrate how parameter-aware querying is beneficial in both
      detecting and removing noise. We also propose a more robust structure descriptor
      based on principal components analysis that better identifies anisotropic detail
      at the sub-kernel level. We illustrate the effectiveness of our approach in
      several example scenes and show significant improvements when rendering complex
      caustics compared to previous methods.

PMID- 23956480
TI  - Diverse Effects of Women's Employment on Fertility: Insights From Italy and
      Poland: Diverses consequences de l'emploi des femmes sur la fecondite: quelques
      informations a partir des cas de l'Italie et de la Pologne.
AB  - In this paper, we look into how country-specific factors shape the
      interrelationship between childbearing and women's labor supply. To this end, we
      compare Italy and Poland, two low-fertility countries where the country-specific
      obstacles to work and family reconciliation are similarly strong but which differ
      in the history of women's labor supply and the extent to which couples' material
      aspirations are satisfied by men's earnings. Our findings show that women's
      employment clearly conflicts with childbearing in Italy, while in Poland women
      tend to combine the two activities, despite the similar difficulties they face.
      These results challenged the standard microeconomic explanations and point to the
      importance of other country-specific factors, apart from conditions for work and
      family reconciliation, in shaping women's employment and fertility decisions,
      such as economic incentives or culturally rooted behavioral patterns. Overall,
      our study provides thus foundations for explaining the variation in the
      relationship between women's employment and fertility in an enlarged Europe.

PMID- 23956481
TI  - Small Effects of Selective Migration and Selective Survival in Retrospective
      Studies of Fertility: Faibles effets de selection de la migration et de la
      mortalite sur la fecondite dans les etudes retrospectives.
AB  - In this study, we assess the accuracy of fertility estimates that stem from the
      retrospective information that can be derived from an existing cross-sectional
      population. Swedish population registers contain information on the childbearing
      of all people ever registered as living in Sweden, and thus allow us to avoid
      problems of selectivity by the virtue of survival or nonemigration when
      estimating the fertility measures for previous calendar periods. We calculate two
      types of fertility rates for each year in 1961-1999: (i) rates that are based on
      the population that was living in Sweden at the end of 1999, and (ii) rates that
      also include information on people who had died or emigrated before the turn of
      the twentieth century. We find that the omission of information on individuals
      who had emigrated or died, as the situation would be in any demographic survey,
      most often have negligible effects on fertility measures. However, first-birth
      rates of immigrants gradually become more biased as we move back in time from
      1999 so that they increasingly tend to over-estimate the true fertility of that
      population.

PMID- 23956482
TI  - Unauthorized Immigration to the United States: Annual Estimates and Components of
      Change, by State, 1990 to 2010.
AB  - We describe a method for producing annual estimates of the unauthorized immigrant
      population in the United Sates and components of population change, for each
      state and D.C., for 1990 to 2010. We quantify a sharp drop in the number of
      unauthorized immigrants arriving since 2000, and we demonstrate the role of
      departures from the population (emigration, adjustment to legal status, removal
      by the Department of Homeland Security (DHS), and deaths) in reducing population
      growth from one million in 2000 to population losses in 2008 and 2009. The number
      arriving in the U.S. peaked at more than one million in 1999 to 2001, and then
      declined rapidly through 2009. We provide evidence that population growth stopped
      after 2007 primarily because entries declined and not because emigration
      increased during the economic crisis. Our estimates of the total unauthorized
      immigrant population in the U.S. and in the top ten states are comparable to
      those produced by DHS and the Pew Hispanic Center. For the remaining states and
      D.C., our data and methods produce estimates with smaller ranges of sampling
      error.

PMID- 23956483
TI  - Deconstructing Community for Conservation: Why Simple Assumptions are Not
      Sufficient.
AB  - Many conservation policies advocate engagement with local people, but
      conservation practice has sometimes been criticised for a simplistic
      understanding of communities and social context. To counter this, this paper
      explores social structuring and its influences on conservation-related behaviours
      at the site of a conservation intervention near Pipar forest, within the Seti
      Khola valley, Nepal. Qualitative and quantitative data from questionnaires and
      Rapid Rural Appraisal demonstrate how links between groups directly and
      indirectly influence behaviours of conservation relevance (including existing and
      potential resource-use and proconservation activities). For low-status groups the
      harvesting of resources can be driven by others' preference for wild foods,
      whilst perceptions of elite benefit-capture may cause reluctance to engage with
      future conservation interventions. The findings reiterate the need to avoid
      relying on simple assumptions about 'community' in conservation, and particularly
      the relevance of understanding relationships between groups, in order to
      understand natural resource use and implications for conservation.

PMID- 23956484
TI  - Alternating copolymerization of carbon dioxide and cyclohexene oxide catalyzed by
      salen CoIII(acetate) complexes.
AB  - A series of CoIII carboxylate based upon N,N,O,O-tetradentate Schiff base ligand
      framework have been prepared. X-ray diffraction analysis confirms that these
      Schiff base CoIII carboxylate are all monomeric species with a six-coordinated
      central Co in their solid structures. The activities and polycarbonate
      selectivity of these complexes toward the copolymerization of epoxide
      (cyclohexene oxide and propylene oxide) and carbon dioxide have been investigated
      in the presence of bis(triphenylphosphine)iminium chloride. Copolymerization
      experiments indicate that [bis(alpha-methyl-3,5-di-tertbutyl-salicylaldehyde)
      ethylenediiminato] CoIIIOOCH3 exhibits the highest activity and polycarbonate
      selectivity among these CoIII carboxylate. The resultant copolymer contained
      almost 100 % carbonate linkages with the molecular weight up to 71.8 kg mol-1 as
      well as narrow polymer dispersity index (polymer dispersity index = 1.5). The
      substituents and the mode of the bridging part between the two nitrogen atoms
      both exert significant influences upon the progress of the copolymerizations,
      influencing both the polycarbonate selectivity and the rate of copolymerization.

PMID- 23956485
TI  - Factors affecting the TMPTA radical polymerization photoinitiated by
      phenyltrialkylborates paired with tri-cationic hemicyanine dye. Kinetic studies.
AB  - This article introduces tri-cationic hemicyanine dye employed as a visible-light
      photoinitiator of acrylic monomers polymerization. This dye, in combination with
      borate anions, was found to be a very effective photoinitiating system. The
      kinetics of trimethylolpropane triacrylate polymerization was studied by a
      microcalorimetric method. The photoredox pair concentration, the co-initiator
      structure as well as the light intensity strongly affected the progress of the
      polymerization, leading, for example, to an increase in the polymerization rate
      and quantum yield of the process. The efficiency of these photoinitiators was
      discussed on the basis of the free energy change for electron transfer from a
      borate anion to an excited hemicyanine dye cation. The ?Gel values were estimated
      for photoredox pairs containing a series of phenyltrialkylborate anions and one
      styrylpyridinium dye cation. The relationship between the rate of polymerization
      and the free energy of activation for electron transfer reaction gives the
      dependence predicted by the classical theory of electron transfer. The
      photoinitiating abilities of the selected novel photoredox pairs (BPB61, BPB7,
      BPB8, and BPB9) are comparable with the photoinitiating efficiency of
      commercially available photoinitiators.

PMID- 23956486
TI  - Multimodal signaling in the Small Torrent Frog (Micrixalus saxicola) in a complex
      acoustic environment.
AB  - Many animals use multimodal (both visual and acoustic) components in courtship
      signals. The acoustic communication of anuran amphibians can be masked by the
      presence of environmental background noise, and multimodal displays may enhance
      receiver detection in complex acoustic environments. In the present study, we
      measured sound pressure levels of concurrently calling males of the Small Torrent
      Frog (Micrixalus saxicola) and used acoustic playbacks and an inflatable balloon
      mimicking a vocal sac to investigate male responses to controlled unimodal
      (acoustic) and multimodal (acoustic and visual) dynamic stimuli in the frogs'
      natural habitat. Our results suggest that abiotic noise of the stream does not
      constrain signal detection, but males are faced with acoustic interference and
      masking from conspecific chorus noise. Multimodal stimuli elicited greater
      response from males and triggered significantly more visual signal responses than
      unimodal stimuli. We suggest that the vocal sac acts as a visual cue and improves
      detection and discrimination of acoustic signals by making them more salient to
      receivers amidst complex biotic background noise.

PMID- 23956488
TI  - A class of multivariate distribution-free tests of independence based on graphs.
AB  - A class of distribution-free tests is proposed for the independence of two
      subsets of response coordinates. The tests are based on the pairwise distances
      across subjects within each subset of the response. A complete graph is induced
      by each subset of response coordinates, with the sample points as nodes and the
      pairwise distances as the edge weights. The proposed test statistic depends only
      on the rank order of edges in these complete graphs. The response vector may be
      of any dimensions. In particular, the number of samples may be smaller than the
      dimensions of the response. The test statistic is shown to have a normal limiting
      distribution with known expectation and variance under the null hypothesis of
      independence. The exact distribution free null distribution of the test statistic
      is given for a sample of size 14, and its Monte-Carlo approximation is considered
      for larger sample sizes. We demonstrate in simulations that this new class of
      tests has good power properties for very general alternatives.

PMID- 23956489
TI  - Social and Spatial Networks: Kinship Distance and Dwelling Unit Proximity in
      Rural Thailand.
AB  - We address a long hypothesized relationship between the proximity of individuals'
      dwelling units and their kinship association. Better understanding this
      relationship is important because of its implications for contact and association
      among members of a society. In this paper, we use a unique dataset from Nang
      Rong, Thailand which contains dwelling unit locations (GPS) and saturated kinship
      networks of all individuals living in 51 agricultural villages. After presenting
      arguments for a relationship between individuals' dwelling unit locations and
      their kinship relations as well as the particulars of our case study, we
      introduce the data and describe our analytic approach. We analyze how kinship -
      considered as both a system linking collections of individuals in an extended
      kinship network and as dyadic links between pairs of individuals -patterns the
      proximity of dwelling units in rural villages. The results show that in general,
      extended kin live closer to one another than do unrelated individuals. Further,
      the degree of relatedness between kin correlates with the distance between their
      dwelling units. Close kin are more likely to co-reside, a fact which drives much
      of the relationship between kinship relatedness and dwelling unit proximity
      within villages. There is nevertheless suggestive evidence of a relationship
      between kinship association and dwelling unit proximity among kin who do not live
      together.

PMID- 23956487
TI  - Ten unanswered questions in multimodal communication.
AB  - The study of multimodal communication has become an active and vibrant field.
      This special issue of Behavioral Ecology and Sociobiology brings together new
      developments in this rapidly expanding area. In this final contribution to the
      special issue, I look to the future and discuss ten questions in need of further
      work, touching on issues ranging from theoretical modeling and the evolution of
      behavior to molecular mechanisms and the development of behavior. In particular,
      I emphasize that the use of multimodal communication allows animals to switch
      between sensory channels when one channel becomes too noisy, and suggest that a
      better understanding of this process may help us both to understand the evolution
      of multisensory signaling and to predict the success of species facing
      environmental changes that affect signaling channels, such as urbanization and
      climate change. An expanded section is included on the effects of climate change
      on animal communication across sensory channels, urging researchers to pursue
      this topic due to the rapidity with which the environment is currently
      transforming.

PMID- 23956490
TI  - Evolutionary implications of the distribution and variation of the skeletal
      muscles of the anuran lymphatic system.
AB  - Lymphatic return to the circulation in anurans is dependent upon the interaction
      of a number of skeletal muscles and lung deflation. We define character states
      and describe variation of these putative lymphatic skeletal muscles: the M.
      cutaneus pectoris (CP), M. cutaneus dorsi (CD), M. piriformis (P), M. sphincter
      ani cloacalis (SAC), and the complex of the M. gracilis minor/M. abdominal
      crenator (GM/AC). We include examination of over 400 specimens of 377 species
      belonging to 40 of the 42 currently recognized anuran families. Some muscles show
      limited variation (P) or are clearly linked to phylogeny (CP; CD) and thus have
      limited value in the determination of form and function. However, the GM/AC and
      SAC show a high degree of structural variation that appears in taxa across the
      phylogenetic spectrum. This allows us to make phylogenetically independent
      determinations of form and function. We define an ancestral state of the GM and
      conclude that evolution of the GM/AC and SAC has progressed in two directions
      from this ancestral state: toward either elaboration or reduction. Where present,
      the character states of both of these muscle groups were observed in all species
      examined and the number of states correlated within each family as well. The
      degree of development of the GM/AC and SAC compliance pump system is strongly
      correlated with previously determined lymph flux rates in a three species test.
      Our data suggest there may be a relationship between greater elaboration of the
      GM/AC and SAC system and terrestriality among the Anura.

PMID- 23956491
TI  - Fatherhood and Intimate Partner Violence: Bringing the Parenting Role into
      Intervention Strategies.
AB  - A large percentage of men who perpetrate intimate partner violence (IPV) are
      fathers who continue to live with or have visitation with their children. Yet,
      providers rarely consider that fathers who perpetrate IPV may benefit from a
      parent-child focused intervention. Therapeutic work with men, who perpetrate IPV,
      especially with their children, is complex with issues of child safety taking
      precedence. This article is meant to provide: 1) a rationale for considering
      father-child intervention in the context of IPV; 2) specific strategies for
      assessment; 3) guidelines for determining if a father is appropriate for such
      intervention; and 4) a review of treatment approaches that have been developed
      that may assist clinicians in work with this population.

PMID- 23956492
TI  - Synthesis and Characterization of Salicylic Acid-Based Poly(Anhydride-Ester)
      Copolymers.
AB  - A series of poly(anhydride-esters) based on poly(1,10-bis(o-car
      boxyphenoxy)decanoate) (CPD) and poly(1,6-bis(p-carboxyphenoxy)hexane) (p-CPH)
      were synthesized by melt-condensation polymerization. Poly-(anhydride-esters)
      that contain CPD hydrolytically degraded into salicylic acid, however, these
      homopolymers have mechanical and thermal characteristics that limit their use in
      clinical applications. The synthesis and characterization of copolymers of CPD
      with p-CPH, a monomer known to generate mechanically stable homopolymers, was
      investigated. By changing the CPD to p-CPH monomer ratios, the salicylic acid
      loading and thermal/mechanical properties of the copolymers was a controlling
      factor; increasing the CPD concentration increased the salicylate loading but
      decreased the polymer stability; whereas increasing the p-CPH concentration
      increased the thermal and mechanical stability of the copolymers. Specifically,
      decreasing the CPD:p-CPH ratio resulted in lower salicylate loading and increased
      thermal decomposition temperatures. The glass transition temperatures ( degrees
      C) varied from 27 to 38 degrees C, a desirable range for elastomeric biomedical
      implants.

PMID- 23956493
TI  - My future self: Young children's ability to anticipate and explain future states.
AB  - Two experiments examine preschool-aged children's ability to anticipate
      physiological states of the self. One hundred and eight 3-, 4-, and 5-year-olds
      were presented with stories and pictorial scenes designed to evoke thought about
      future states such as thirst, cold, and hunger. They were asked to imagine
      themselves in these scenarios and to choose one item from a set of three that
      they would need. Only one of the items could be used to address the future state.
      In both experiments, developmental differences were obtained for correct item
      choices and types of verbal explanations. In Experiment 2, the performance of the
      3- and 4-year-olds was negatively affected by introducing items that were
      semantically associated with the scenarios but did not address the future state,
      whereas the 5-year-olds' performance was not. Results are discussed with respect
      to children's understanding of the future, theory of mind, and inhibitory control
      skills.

PMID- 23956494
TI  - Post-Separation Abuse of Women and their Children: Boundary-setting and Family
      Court Utilization among Victimized Mothers.
AB  - Continued abuse of themselves and their children is a concern for many mothers
      leaving intimate partner violence (IPV) perpetrating husbands. This research
      examines women's responses to abuse committed by ex-husbands with whom they had
      undergone custody disputes. In-depth, qualitative interviews were conducted with
      19 mothers who had divorced IPV-perpetrating husbands between one and three years
      prior. Participants were located through publicly available family court divorce
      records and interviews were examined using analytic induction. Women's strategies
      to protect themselves and their children from abuse involved setting boundaries
      to govern their interactions with ex-husbands. Mothers often turned to family
      court for assistance in setting boundaries to keep children safe, but found that
      family court did not respond in ways they believed protected their children.
      Conversely, when women turned to the justice system for restraining orders or
      called the police for help against IPV, they generally found the justice system
      responsive.

PMID- 23956495
TI  - Toward a comprehensive framework for the spatiotemporal statistical analysis of
      longitudinal shape data.
AB  - This paper proposes an original approach for the statistical analysis of
      longitudinal shape data. The proposed method allows the characterization of
      typical growth patterns and subject-specific shape changes in repeated time
      series observations of several subjects. This can be seen as the extension of
      usual longitudinal statistics of scalar measurements to high-dimensional shape or
      image data. The method is based on the estimation of continuous subject-specific
      growth trajectories and the comparison of such temporal shape changes across
      subjects. Differences between growth trajectories are decomposed into
      morphological deformations, which account for shape changes independent of the
      time, and time warps, which account for different rates of shape changes over
      time. Given a longitudinal shape data set, we estimate a mean growth scenario
      representative of the population, and the variations of this scenario both in
      terms of shape changes and in terms of change in growth speed. Then, intrinsic
      statistics are derived in the space of spatiotemporal deformations, which
      characterize the typical variations in shape and in growth speed within the
      studied population. They can be used to detect systematic developmental delays
      across subjects. In the context of neuroscience, we apply this method to analyze
      the differences in the growth of the hippocampus in children diagnosed with
      autism, developmental delays and in controls. Result suggest that group
      differences may be better characterized by a different speed of maturation rather
      than shape differences at a given age. In the context of anthropology, we assess
      the differences in the typical growth of the endocranium between chimpanzees and
      bonobos. We take advantage of this study to show the robustness of the method
      with respect to change of parameters and perturbation of the age estimates.

PMID- 23956496
TI  - A Passive Radio-Frequency Identification (RFID) Gas Sensor With Self-Correction
      Against Fluctuations of Ambient Temperature.
AB  - Uncontrolled fluctuations of ambient temperature in the field typically greatly
      reduce accuracy of gas sensors. In this study, we developed an approach for the
      self-correction against fluctuations of ambient temperature of individual gas and
      vapor sensors. The main innovation of our work is in the temperature correction
      which is accomplished without the need for a separate uncoated reference sensor
      or a separate temperature sensor. Our sensors are resonant inductor-capacitor
      resistor (LCR) transducers coated with sensing materials and operated as
      multivariable passive (battery-free) radio-frequency identification (RFID)
      sensors. Using our developed approach, we performed quantitation of an exemplary
      vapor over the temperature range from 25 to 40  degrees C. This technical
      solution will be attractive in numerous applications where temperature
      stabilization of a gas sensor or addition of auxiliary temperature or uncoated
      reference sensors is prohibitive.

PMID- 23956497
TI  - A Planar Microfluidic Mixer Based on Logarithmic Spirals.
AB  - A passive, planar micromixer design based on logarithmic spirals is presented.
      The device was fabricated using polydimethylsiloxane soft photolithography
      techniques, and mixing performance was characterized via numerical simulation and
      fluorescent microscopy. Mixing efficiency initially declined as Reynolds number
      increased, and this trend continued until a Reynolds number of 15 where a minimum
      was reached at 53%. Mixing efficiency then began to increase reaching a maximum
      mixing efficiency of 86% at Re = 67. Three-dimensional simulations of fluid
      mixing in this design were compared to other planar geometries such as the
      Archimedes spiral and Meandering-S mixers. The implementation of logarithmic
      curvature offers several unique advantages that enhance mixing, namely a variable
      cross-sectional area and a logarithmically varying radius of curvature that
      creates 3-D Dean vortices. These flow phenomena were observed in simulations with
      multilayered fluid folding and validated with confocal microscopy. This design
      provides improved mixing performance over a broader range of Reynolds numbers
      than other reported planar mixers, all while avoiding external force fields, more
      complicated fabrication processes, and the introduction of flow obstructions or
      cavities that may unintentionally affect sensitive or particulate-containing
      samples. Due to the planar design requiring only single-step lithographic
      features, this compact geometry could be easily implemented into existing micro
      total analysis systems requiring effective rapid mixing.

PMID- 23956498
TI  - Microfluidic jet injection for delivering macromolecules into cells.
AB  - We present a microfluidic based injection system designed to achieve
      intracellular delivery of macromolecules by directing a picoliter-jet of a
      solution towards individual cells. After discussing the concept, we present
      design specification and criteria, elucidate performance and discuss results. The
      method has the potential to be quantitative and high throughput, overcoming
      limitations of current intracellular delivery protocols.

PMID- 23956499
TI  - A MEMS differential viscometric sensor for affinity glucose detection in
      continuous glucose monitoring.
AB  - Micromachined viscometric affinity glucose sensors have been previously
      demonstrated using vibrational cantilever and diaphragm. These devices featured a
      single glucose detection module that determines glucose concentrations through
      viscosity changes of glucose-sensitive polymer solutions. However, fluctuations
      in temperature and other environmental parameters might potentially affect the
      stability and reliability of these devices, creating complexity in their
      applications in subcutaneously implanted continuous glucose monitoring (CGM). To
      address these issues, we present a MEMS differential sensor that can effectively
      reject environmental disturbances while allowing accurate glucose detection. The
      sensor consists of two magnetically driven vibrating diaphragms situated inside
      microchambers filled with a boronic-acid based glucose-sensing solution and a
      reference solution insensitive to glucose. Glucose concentrations can be
      accurately determined by characteristics of the diaphragm vibration through
      differential capacitive detection. Our in-vitro and preliminary in-vivo
      experimental data demonstrate the potential of this sensor for highly stable
      subcutaneous CGM applications.

PMID- 23956500
TI  - A Tutorial on Rank-based Coefficient Estimation for Censored Data in Small- and
      Large-Scale Problems.
AB  - The analysis of survival endpoints subject to right-censoring is an important
      research area in statistics, particularly among econometricians and
      biostatisticians. The two most popular semiparametric models are the proportional
      hazards model and the accelerated failure time (AFT) model. Rank-based estimation
      in the AFT model is computationally challenging due to optimization of a non
      smooth loss function. Previous work has shown that rank-based estimators may be
      written as solutions to linear programming (LP) problems. However, the size of
      the LP problem is O(n2 + p) subject to n2 linear constraints, where n denotes
      sample size and p denotes the dimension of parameters. As n and/or p increases,
      the feasibility of such solution in practice becomes questionable. Among data
      mining and statistical learning enthusiasts, there is interest in extending
      ordinary regression coefficient estimators for low-dimensions into high
      dimensional data mining tools through regularization. Applying this recipe to
      rank-based coefficient estimators leads to formidable optimization problems which
      may be avoided through smooth approximations to non-smooth functions. We review
      smooth approximations and quasi-Newton methods for rank-based estimation in AFT
      models. The computational cost of our method is substantially smaller than the
      corresponding LP problem and can be applied to small- or large-scale problems
      similarly. The algorithm described here allows one to couple rank-based
      estimation for censored data with virtually any regularization and is exemplified
      through four case studies.

PMID- 23956501
TI  - Lipoxin a4 preconditioning and postconditioning protect myocardial
      ischemia/reperfusion injury in rats.
AB  - This study aims to investigate the pre- and postconditioning effects of lipoxin
      A4 (LXA4) on myocardial damage caused by ischemia/reperfusion (I/R) injury.
      Seventy-two rats were divided into 6 groups: sham groups (C1 and C2), I/R groups
      (I/R1 and I/R2), and I/R plus LXA4 preconditioning and postconditioning groups
      (LX1 and LX2). The serum levels of IL-1 beta , IL-6, IL-8, IL-10, TNF- alpha ,
      and cardiac troponin I (cTnI) were measured. The content and the activity of
      Na(+)-K(+)-ATPase as well as the superoxide dismutase (SOD), and malondialdehyde
      (MDA) levels were determined. Along with the examination of myocardium
      ultrastructure and ventricular arrhythmia scores (VAS), connexin 43 (Cx43)
      expression were also detected. Lower levels of IL-1 beta , IL-6, IL-8, TNF- alpha
      , cTnI, MDA content, and VAS and higher levels of IL-10, SOD activity, Na(+)-K(+)
      ATPase content and activity, and Cx43 expression appeared in LX groups than I/R
      groups. Besides, H&E staining, TEM examination as well as analysis of gene, and
      protein confirmed that LXA4 preconditioning was more effective than
      postconditioning in preventing arrhythmogenesis via the upregulation of Cx43.
      That is, LXA4 postconditioning had better protective effect on Na(+)-K(+)-ATPase
      and myocardial ultrastructure. 

PMID- 23956502
TI  - Inflammation and immune response in COPD: where do we stand?
AB  - Increasing evidence indicates that chronic inflammatory and immune responses play
      key roles in the development and progression of COPD. Recent data provide
      evidence for a role in the NLRP3 inflammasome in the airway inflammation observed
      in COPD. Cigarette smoke activates innate immune cells by triggering pattern
      recognition receptors (PRRs) to release "danger signal". These signals act as
      ligands to Toll-like receptors (TLRs), triggering the production of cytokines and
      inducing innate inflammation. In smokers who develop COPD there appears to be a
      specific pattern of inflammation in the airways and parenchyma as a result of
      both innate and adaptive immune responses, with the predominance of CD8+ and CD4+
      cells, and in the more severe disease, with the presence of lymphoid follicles
      containing B lymphocytes and T cells. Furthermore, viral and bacterial infections
      interfere with the chronic inflammation seen in stable COPD and exacerbations via
      pathogen-associated molecular patterns (PAMPs). Finally, autoimmunity is another
      novel aspect that may play a critical role in the pathogenesis of COPD. This
      review is un update of the currently discussed roles of inflammatory and immune
      responses in the pathogenesis of COPD. 

PMID- 23956503
TI  - Fractalkine (CX3CL1) and its receptor CX3CR1 may contribute to increased
      angiogenesis in diabetic placenta.
AB  - Chemokine CX3CL1 is unique, possessing the ability to act as a dual agent:
      chemoattractant and adhesive compound. Acting via its sole receptor CX3CR1,
      CX3CL1 participates in many processes in human placental tissue, including
      inflammation and angiogenesis. Strongly upregulated by hypoxia and/or
      inflammation-induced inflammatory cytokines secretion, CX3CL1 may act locally as
      a key angiogenic factor. Both clinical observations and histopathological studies
      of the diabetic placenta have confirmed an increased incidence of hypoxia and
      inflammatory reactions with defective angiogenesis. In this study we examined
      comparatively (diabetes class C complicated versus normal pregnancy) the
      correlation between CX3CL1 content in placental tissue, the mean CX3CR1
      expression, and density of the network of placental microvessels. A sandwich
      enzyme immunoassay was applied for CX3CL1 measurement in placental tissue
      homogenates, whereas quantitative immunohistochemical techniques were used for
      the assessment of CX3CR1 expression and the microvascular density. Significant
      differences have been observed for all analyzed parameters between the groups.
      The mean concentration of CX3CL1 in diabetes was increased and accompanied by
      augmented placental microvessel density as well as a higher expression of CX3CR1.
      In conclusion, we suggest involvement of CX3CL1/CX3CR1 signaling pathway in the
      pathomechanism of placental microvasculature remodeling in diabetes class C. 

PMID- 23956504
TI  - Ox-LDL promotes migration and adhesion of bone marrow-derived mesenchymal stem
      cells via regulation of MCP-1 expression.
AB  - Bone marrow-derived mesenchymal stem cells (bmMSCs) are the most important cell
      source for stem cell transplant therapy. The migration capacity of MSCs is one of
      the determinants of the efficiency of MSC-based transplant therapy. Our recent
      study has shown that low concentrations of oxidized low-density lipoprotein (ox
      LDL) can stimulate proliferation of bmMSCs. In this study, we investigated the
      effects of ox-LDL on bmMSC migration and adhesion, as well as the related
      mechanisms. Our results show that transmigration rates of bmMSCs and cell-cell
      adhesion between bmMSCs and monocytes are significantly increased by treatments
      with ox-LDL in a dose- and time-dependent manner. Expressions of ICAM-1, PECAM-1,
      and VCAM-1 as well as the levels of intracellular Ca(2+) are also markedly
      increased by ox-LDL in a dose-dependent manner. Cytoskeleton analysis shows that
      ox-LDL treatment benefits to spreading of bmMSCs and organization of F-actin
      fibers after being plated for 6 hours. More interestingly, treatments with ox-LDL
      also markedly increase expressions of LOX-1, MCP-1, and TGF- beta ; however, LOX
      1 antibody and MCP-1 shRNA markedly inhibit ox-LDL-induced migration and adhesion
      of bmMSCs, which suggests that ox-LDL-induced bmMSC migration and adhesion are
      dependent on LOX-1 activation and MCP-1 expression. 

PMID- 23956506
TI  - Plagiarism: Is it time to rethink our approach?

PMID- 23956505
TI  - Development and treatments of inflammatory cells and cytokines in spinal cord
      ischemia-reperfusion injury.
AB  - During aortic surgery, interruption of spinal cord blood flow might cause spinal
      cord ischemia-reperfusion injury (IRI). The incidence of spinal cord IRI after
      aortic surgery is up to 28%, and patients with spinal cord IRI might suffer from
      postoperative paraplegia or paraparesis. Spinal cord IRI includes two phases. The
      immediate spinal cord injury is related to acute ischemia. And the delayed spinal
      cord injury involves both ischemic cellular death and reperfusion injury.
      Inflammation is a subsequent event of spinal cord ischemia and possibly a major
      contributor to spinal cord IRI. However, the development of inflammatory
      mediators is incompletely demonstrated. And treatments available for inflammation
      in spinal cord IRI are insufficient. Improved understanding about spinal cord IRI
      and the development of inflammatory cells and cytokines in this process will
      provide novel therapeutic strategies for spinal cord IRI. Inflammatory cytokines
      (e.g., TNF- alpha and IL-1) may play an important role in spinal cord IRI. For
      treatment of several intractable autoimmune diseases (e.g., rheumatoid
      arthritis), where inflammatory cytokines are involved in disease progression,
      anti-inflammatory cytokine antagonist is now available. Hence, there is great
      potential of anti-inflammatory cytokine antagonist for therapeutic use of spinal
      cord IRI. We here review the mediators and several possibilities of treatment in
      spinal cord IRI. 

PMID- 23956507
TI  - Retraction notice.

PMID- 23956509
TI  - Complications of laparo-endoscopic single-site surgery in urology.
AB  - The objective was to give a general overview of common complications and rates
      reported in the current literature during performance of a variety of urologic
      procedures using laparo-endoscopic single-site surgery or LESS. A search of
      published reports using Pubmed and MEDLINE was performed with the following
      search terms: laparo-endoscopic single-site surgery, LESS or laparo-endoscopic
      single-site surgery complications within the date range of 2005--2011. Studies
      that were deemed appropriate and relevant to the current symposium were chosen
      for review. Overall complication rates were reported as ranging between 10% and
      25%. In general, reconstructive procedures had consistently higher rates of
      complications than their extirpative/ablative counterparts (27% vs. 8%). There
      remain insufficient data to comment on differences in the rates or types of
      complications related to variations in the approach (transperitoneal vs.
      retroperitoneal), site of surgery (upper tract vs. lower tract) or specific
      technique used (instruments, access devices, robotic platforms, etc.).
      Complication rates associated with LESS in urology appear only slightly higher
      than with conventional laparoscopy. However, with proper patient selection and
      careful application of these techniques, proofs of concept and technical
      feasibility have been shown in several series. There continues to be a need for
      more standardization of the technique and reporting as well as more collaborative
      efforts to fully address questions of safety and efficacy of these new
      procedures. 

PMID- 23956508
TI  - Optimal bone health management strategies in patients with prostate cancer.
AB  - Bone health is affected in patients with prostate cancer, both by the disease and
      its treatment. Metastases to bone leads to pain, fractures, and spinal cord
      compression; bone loss due to androgen deprivation therapy (ADT) leads to
      osteoporosis and its complications. Both these scenarios are a major cause of
      morbidity and adversely affect the quality of life of these patients. Maintaining
      an optimum bone health throughout the natural course of prostate cancer is an
      important aspect in the management of this disease. An understanding of the
      complex interplay between osteoclasts, osteoblasts, receptor activator of nuclear
      factor kappaB (RANK), and various other tyrosine kinases involved in the
      pathophysiology of bone metastases is essential. Zoledronic acid (ZA), an
      intravenously administered bisphosphonate, and Denosumab, a subcutaneously
      administered inhibitor of nuclear factor B ligand (RANKL), have already been
      approved by Food and Drug Administration (FDA) for their use in treatment of bone
      metastases. This article discusses the pathophysiology of bone metastases and
      bone loss due to ADT in prostate cancer, role of biomarkers, newer modalities of
      imaging, World Health Organization (WHO)/FRAX nomogram in evaluation of these
      patients, utility of currently available drugs and evidence supporting their use,
      and newer therapeutic agents like alpha-emitting Radium-223, endothelin-A
      receptor antagonists (Atrasentan and Zibotentan) and the proto-oncogene tyrosine
      protein kinase (SRC) inhibitor, Dasatinib. 

PMID- 23956510
TI  - Deceased donor renal transplantation at army hospital research and referral: Our
      experience.
AB  - CONTEXT: In India, there are a large number of end-stage renal disease (ESRD)
      patients waiting for renal transplant. Deceased donor organ transplantation
      (DDOT) is the possible solution to bridge the disparity between organ supply and
      demand. The concept of expanded criteria donors (ECDs) was developed to combat
      the huge discrepancy between demand and organ availability. However, ECD kidneys
      have a higher propensity for delayed graft function (DGF), and therefore worse
      long-term survival. We present our experience of deceased donor renal
      transplantation. AIMS: We report single centre experience on DDOT including ECDs
      vis-a-vis patient/graft survival, graft function in terms of serum creatinine
      (SCr), rejection episodes, and delayed graft function in 44 DDOT. MATERIALS AND
      METHODS: Between August 1998 and April 2011, 44 renal transplants from 35
      deceased donors were performed, of which 37.2% were expanded criteria donors.
      Results were analyzed in terms of age of donor, terminal SCr, graft ischemia
      time, graft function, post-transplant complications, and graft and patient
      survival. All recipients received sequential triple drug immunosuppression and
      induction with rabbit antithymocyte globulin (rATG). The induction is commenced
      by giving first dose of rATG intraoperatively (dose 1.5 mg/kg) and subsequent
      rATG infusions were administered daily for a minimum of 5 and maximum of 7 doses
      depending on initial graft function. RESULTS: We have been able to achieve a mean
      cold ischemia time of 6.25 +/- 2.55 h due to the coordinated team efforts.
      Delayed graft function occurred in 34% patients and 31.8% had prolonged drainage.
      There were no urinary leaks. Seven (16%) patients had biopsy-proven rejection
      episodes, all of which were reversed with treatment. Two patients underwent graft
      nephrectomy. One of these was due to hyperacute rejection and another due to
      anastomotic hemorrhage. One-year graft survival was 92.4% and the patient
      survival was 83.8%. CONCLUSION: Deceased donor renal transplants have
      satisfactory graft function and patient survival despite the high incidence of
      delayed graft function. Retrieving kidneys from marginal donors can add to the
      donor pool.

PMID- 23956511
TI  - Paratesticular rhabdomyosarcoma in young adults: A tertiary care institute
      experience.
AB  - INTRODUCTION: Paratesticular rhabdomyosarcoma (RMS) is a rare tumor arising from
      the mesenchymal tissues of the spermatic cord, epididymis, testis and testicular
      tunics. It represents only 7% of all patients entered in the Intergroup
      Rhabdomyosarcoma Study (IRS) and 17% of all malignant intrascrotal tumors in
      children less than 15 years old. We present our experience in combined modality
      management of 10 successive patients of paratesticular RMS. MATERIAL AND METHODS:
      We retrospectively reviewed 10 patients of paratesticular RMS treated in our
      institute from July 2004 to December 2010. Clinical characteristics and treatment
      modality in form of surgery and chemotherapy (CCT) were noted. Statistical
      analysis was done with regards to progression-free survival (PFS) and overall
      survival (OS) using Kaplan-Meier survival analysis. RESULTS: The median age of
      the patients was 16.5 years. The median duration of symptoms was 5 months. Five
      patients had retroperitoneal lymphadenopathy (RPLAP) while three had lung
      metastases and one had orbital metastases. All patients underwent high inguinal
      orchidectomy followed by systemic chemotherapy (CCT). Retroperitoneal node
      dissection was not a required staging procedure. Four patients had partial
      response to treatment while six had complete response. Mean duration of PFS was
      48 months and mean OS was 56 months. CONCLUSIONS: Paratesticular RMS are rare
      neoplasms with aggressive growth patterns. Cure rates have dramatically improved
      and 60% of patients in our series had complete response. This success is due to
      development of multimodality and risk adapted treatment approaches.

PMID- 23956512
TI  - Living donor transplant options in end-stage renal disease patients with ABO
      incompatibility.
AB  - INTRODUCTION: The options available to CKD 5 patients with donor shortage due to
      incompatibilities is to either get enlisted in cadaver transplant program or opt
      for three other alternatives viz; ABO-incompatible transplant (ABO-I), ABO
      incompatible transplant with Rituximab (ABO-R) or paired-kidney exchange
      transplant (PKE). At our institute we have performed ABO-I, ABO-R and PKE
      transplants and we are presenting the results of these transplants performed at
      our institution. Here, we report our experiences of living donor kidney
      transplantation in highly sensitized patients. OBJECTIVE: To review the options
      available to CKD 5 patients with incompatible donor. MATERIALS AND METHODS:
      Between January 2008 and June 2011, 7 PKE, 26 ABO-I and 7 ABO-R transplants were
      carried out at our institute. Evaluation of both the recipients and donors
      involved biochemical, serological and radiological investigations. In case of
      PKE, recipients were operated simultaneously in different operation theaters. In
      ABO-I splenectomy was done while in ABO-R was given. Post-transplant the
      recipient management protocol remained the same. Expenditure following each
      transplant was calculated. RESULTS: The graft and patient survival of ABO-I, ABO
      R and PKE transplants 12-18 months after transplant were 78.9%:80%, 85.7%:85.7%
      and 100%:100%, respectively. CONCLUSIONS: The inclusion of Rituximab in the
      transplant protocol appears promising. The existing donor shortage could be
      addressed by encouraging other options like PKE. The limiting factor for ABO-R
      and PKE transplants is time and cost, respectively. The decision depends on the
      informed consent between the patient and the nephrologists.

PMID- 23956513
TI  - Sexual outcomes after organ potency-sparing surgery and glans reconstruction in
      patients with penile carcinoma.
AB  - INTRODUCTION: Radical surgery is the "gold standard" for treatment of invasive
      penile carcinoma but very poor aesthetic, functional and psychological outcomes
      have been reported. Our purpose was to assess the impact of organ potency-sparing
      surgery in locally confined carcinoma of the penis. MATERIALS AND METHODS: We
      evaluated retrospectively 42 patients with early penile cancer (Ta,T1,T2),
      treated with glandulectomy and glanduloplasty with urethral mucosa and sparing of
      cavernosal apexes, or glandulectomy and limited apical resection in cases of
      Stage T2. Sexual function, ejaculation and libido were evaluated with an IIEF-15
      questionnaire before the appearance of neoplasia (about three months before the
      surgery) and six months after surgery. Quality of life was evaluated by the
      Bigelow-Young questionnaire. The scores relating to two weeks prior to the
      surgery have been compared to those obtained six months after surgery. The
      statistical analysis was conducted using t-Student for repeated measures and
      analysis of variance. RESULTS: Six months after surgery 73% of patients reported
      spontaneous rigid erections, 60% coital activity while 76% of the group treated
      with urethral glanduloplasty reported normal ejaculation and orgasm, regained an
      average of 35 days after surgery. The average IIEF-15 scores reported in the
      entire series in the domains of erection, libido and coital activity of the pre
      cancer period were not statistically different than those recorded six months
      after surgery. In the group treated with glandular reconstruction, pre-and
      postoperative IIEF-15 mean scores related to ejaculation and orgasm domains were
      not significantly different. Mean scores of Bigelow-Young questionnaires related
      to sexual pleasure, familial, social and professional relationships showed
      significant improvement after surgery. CONCLUSIONS: Potency sparing-sparing
      surgical treatments have a positive impact on a wide spectrum of the patient's
      life including family relationships, and social and working conditions.

PMID- 23956514
TI  - Dorsal onlay vaginal graft urethroplasty for female urethral stricture.
AB  - INTRODUCTION: Female urethral stricture is an underdiagnosed and overlooked cause
      of female bladder outlet obstruction. The possible etiologies may be infection,
      prior dilation, difficult catheterization with subsequent fibrosis, urethral
      surgery, trauma, or idiopathic. We present our technique and results of dorsal
      onlay full thickness vaginal graft urethroplasty for female urethral stricture.
      MATERIALS AND METHODS: A retrospective review was performed on 16 female patients
      with mid-urethral stricture who underwent dorsal onlay vaginal graft
      urethroplasty from January 2007 to June 2011. Of these, 13 patients had
      previously undergone multiple Hegar dilatations, three had previous internal
      urethrotomies. The preoperative work up included detailed voiding history, local
      examination, uroflowmetry, calibration, and micturating cystourethrogram.
      RESULTS: All patients had mid-urethral stricture. Mean age was 47.5 years. Mean
      Qmax improved from 6.2 to 27.6 ml/s. Mean residual volume decreased from 160 to
      20 ml. Mean duration of follow-up was 24.5 months (6 months to 3 years). Only one
      patient required self-calibration for 6 months after which her stricture
      stabilized. None of the patient was incontinent. CONCLUSION: Dorsal vaginal onlay
      graft urethroplasty could be considered as an effective way to treat female
      urethral stricture.

PMID- 23956515
TI  - Unexplained occurrence of multiple de novo pseudoaneurysms in patients with
      chronic kidney disease undergoing angioembolization for bleeding following
      percutaneous renal intervention: Are we dealing with infection or vasculitis?
AB  - BACKGROUND AND OBJECTIVES: Patients with chronic kidney disease (CKD) are more
      prone for bleeding following percutaneous renal intervention, as compared to
      those with normal renal function. Causes are multi-factorial. Finding multiple
      aneurysms away from the site of renal intervention following initial
      angioembolization for hemorrhage is very unusual in these patients. MATERIALS AND
      METHODS: Clinical and radiological findings of all the patients who underwent
      renal angiography for post-intervention bleed for a period of 5 years were
      reviewed and analyzed. RESULTS: A total of 29 patients required angiography for
      post-intervention hemorrhage. Six patients had recurrence of hemorrhage for which
      they underwent repeat angiography. Four of these patients had appearance of
      multiple new aneurysms away from the site of percutaneous nephrostomy
      (PCN)/percutaneous nephrolithotomy (PNL) puncture and the site of previous
      bleeding. All the patients had CKD (creatinine >2.5 mg/dl). They were on
      prolonged preoperative urinary diversion and had polymicrobial urinary infection.
      Three patients had candiduria. None of these patients had re-bleeding after
      repeat embolization and treatment with antibacterial and antifungal agents.
      CONCLUSIONS: Development of multiple aneurysms away from the sites of punctures
      in patients with CKD following percutaneous intervention is very unusual. Its
      causation including infection with bacteria and fungus, reaction of embolizing
      material, and angiopathy needs to be explored.

PMID- 23956516
TI  - Partial reimplantation of Tenckhoff catheter for channel perforation and
      aneurysm: A case series.
AB  - Tenckhoff catheter placement is a well established procedure to facilitate
      continuous ambulatory peritoneal dialysis (CAPD) in end-stage renal disease
      (ESRD) management. The removal and replacement of the catheter following
      complications adds morbidity in an already immunocompromised patient of ESRD. A
      salvage procedure with partial replacement was undertaken in four patients on
      CAPD. By catheter repositioning, the complications of catheter removal (like
      wound hematoma, abscess, need of break-in period hemodialysis) and of reinsertion
      (like leak, obstruction, migration, infection and failure) are avoided. It also
      reduced the economic burden of insertion in a new catheter. 

PMID- 23956517
TI  - Robotic repair of a rare case of symptomatic "Ureterosciatic Hernia".
AB  - Ureterosciatic hernia (USH) is a rarely described entity and is an extremely rare
      cause of refractory flank pain. We report the diagnostic dilemma, and sequential
      endourological and finally the successful robotic management of one such
      symptomatic USH in an elderly woman who had presented with ipsilateral refractory
      flank pain, hydroureteronephrosis, and compromised renal function. We have also
      reviewed the current literature regarding the etiopathogenesis, presentation,
      diagnosis, and management of USHs. To the best of our knowledge, this is the
      first such case to describe the robotic-assisted laparoscopic management of a
      case of USH. 

PMID- 23956518
TI  - Spontaneous transvaginal bowel evisceration.
AB  - Transvaginal prolapse of bowel segments after major abdominal surgery is of rare
      occurrence and is commonly reported to follow after hysterectomy and enterocele
      repair. However, spontaneous bowel evisceration through vagina following
      cystectomy is even rare. We report and discuss a case of spontaneous transvaginal
      bowel evisceration in a postmenopausal woman with the intent of increasing its
      awareness among surgeons and proposing a precautionary measure for this entity. 

PMID- 23956519
TI  - Cloacal anomaly with bladder tumor.
AB  - A rare case of squamous cell carcinoma of bladder occurring in a 36-year-old
      female with persistent cloacal anomaly who presented with frequency, urgency,
      dysuria, and recurrent urinary tract infection is reported. Contrast Enhanced
      Computed Tomography with three dimensional reconstruction showed presence of
      bladder tumor and persistent cloaca. She underwent pelvic exenteration and wet
      colostomy. Histopathologic findings revealed locally advanced moderately
      differentiated squamous cell carcinoma. 

PMID- 23956520
TI  - Primary renal angiosarcoma.
AB  - Primary angiosarcoma of the kidney is a rare tumor with only a few case reports
      in the literature. Management is not standardized and the prognosis is poor.
      However, clinicians need to be aware of this uncommon entity. 

PMID- 23956521
TI  - Traumatic rectourethral fistula repair: A potential application of porcine small
      intestinal submucosa.
AB  - Rectourethral fistula is an uncommon but devastating condition. Traumatic
      rectourethral fistula is still uncommon and repair of traumatic rectourethral
      fistula involves a complex procedure. Most of the urologists would prefer to
      repair the fistula through perineal route especially when urethral reconstruction
      is also required. The repaired ends of the fistula are separated with various
      interposition flaps and grafts in order to prevent recurrence. Gracilis
      interposition muscle flap is commonly used. We describe the first case of
      traumatic rectourethral fistula repair in a 45-year-old man using interposition
      of a porcine small intestinal submucosal (BiodesignTM (Surgisis((r))) graft. 

PMID- 23956522
TI  - Role of sonography-guided lithotripsy in renal stone with angiomyolipoma.
AB  - Treatment of angiomyolipoma (AML) of kidney with stone has been challenging for
      urologists. We present our experience of treating the renal stone in the presence
      of AML with shockwave lithotripsy (SWL). Position of the patient with respect to
      the direction of the shockwaves and accurate knowledge of the dimension of the
      focal zone are critical aspects of SWL. Keeping the AML safely away from the
      focal zone at all times during the procedure is only possible by usage of real
      time ultrasonography in lieu of fluoroscopy. 

PMID- 23956523
TI  - Bilateral vesical inguinal hernia: A perineal 'Mickey mouse'.
AB  - Bladder being a content of inguinal hernias is a rare event and it being the sole
      component is extremely uncommon. Usually, elderly obese males are affected and
      symptomatology depends on the extent of bladder involvement. However, recognition
      of this entity is important in the treatment of LUTS as well as to avoid
      inadvertent bladder injury during hernia repair. 

PMID- 23956524
TI  - Trans-umbilical laparo-endoscopic single-site donor nephrectomy without the use
      of a single-port access device.

PMID- 23956525
TI  - Chennai, India to host the 11(th) World Endodontic Congress (International
      Federation of Endodontic Associations) - 2019.

PMID- 23956526
TI  - Minimally invasive dentistry (Endodontics).

PMID- 23956528
TI  - Confocal laser scanning microscopic investigation of ultrasonic, sonic, and
      rotary sealer placement techniques.
AB  - BACKGROUND: Sealers are used to attain an impervious seal between the core
      material and root canal walls. AIM: To compare the depth and percentage of sealer
      penetration with three different placement techniques using confocal laser
      scanning microscopy as the evaluative tool. MATERIALS AND METHODS: Root canals of
      30 single-rooted teeth were prepared to a size of F3 and AH plus sealer with
      Rhodamine B was applied with Ultlrasonic file (Gr-1), lentulospiral (Gr-2), and
      Endoactivator (Gr-3). Canals were obturated with gutta-percha. The roots were
      sectioned at the 3 and 6-mm levels from the apical foramen and were examined on a
      confocal microscope. RESULTS: A statistical significant differences among Gr-1,
      Gr-2, and Gr-3 were found at the 3 and 6-mm level (P < 0.05; ANOVA-Tukey tests)
      for the depth and percentage of sealer penetration except for Gr-1 and Gr-2 at 3
      mm level. Gr-1 showed maximum mean depth of penetration (810 MUm) and maximum
      mean percentage of sealer penetration (64.5) while Gr-3 showed minimum mean depth
      of penetration (112.7 MUm) and minimum mean percentage of sealer penetration
      (26.7). CONCLUSION: Depth and percentage of penetration of sealer is influenced
      by the type of placement technique and by the root canal level with penetration
      decreasing apically.

PMID- 23956527
TI  - Role of Platelet rich fibrin in wound healing: A critical review.
AB  - AIM: The aim is to review and discuss the strategies available for use of
      platelet rich fibrin as healing aid in dentistry. BACKGROUND: Platelet rich
      fibrin (PRF) is a fibrin matrix in which platelet cytokines, growth factors, and
      cells are trapped and may be released after a certain time and that can serve as
      a resorbable membrane. Choukroun and his associates were amongst the pioneers for
      using PRF protocol in oral and maxillofacial surgery to improve bone healing in
      implant dentistry. Autologous PRF is considered to be a healing biomaterial, and
      presently, studies have shown its application in various disciplines of
      dentistry. MATERIALS AND METHODS: By using specific keywords, electronic search
      of scientific papers was carried out on the entire PubMed database with custom
      range of 5 years. The electronic search yielded 302 papers; based on inclusion
      and exclusion criteria which were specifically predetermined, 72 papers were
      identified as suitable to the inclusion criteria and the remaining 230 papers
      were excluded. After adding three more selected papers through hand search, full
      text of all the articles retrieved and review was done. By pooling the extracted
      data from selected papers, the reviewed data was synthesized. CONCLUSION:
      Recently by showing good promising results with use of the PRF, it has proved to
      have a good prospect for its use as healing aid in various aspects of the
      dentistry.

PMID- 23956529
TI  - Quantitative evaluation of apical extrusion of intracanal bacteria using K3,
      Mtwo, RaCe and protaper rotary systems: An in vitro study.
AB  - AIM: This aim of this study was to evaluate the number of bacteria extruded
      apically during root canal preparation using Four Rotary instrumentation
      techniques. MATERIALS AND METHODS: A total of 50 extracted mandibular premolars
      were selected, access cavities prepared and inserted in to rubber stoppers of 10
      mL glass vial. Root canals were contaminated with a suspension of Enterococcus
      faecalis (E. faecalis) American Type Culture Collection (ATCC) 29212 and
      incubated for 24 h at 37 degrees C. Debris extruded from the apical foramen
      during instrumentation was collected into vials. The numbers of Colony-forming
      units were determined for each sample. STATISTICAL ANALYSIS: The data obtained
      were analyzed using the one-way ANOVA followed by post-hoc tukey's test with a P
      = 0.05 as the level for statistical significance. RESULTS: Results suggested a
      statistically significant difference in the number of colony forming units
      between four experimental rotary Nickel-Titanium instrumentation groups (P <
      0.001). CONCLUSION: Although, extrusion of bacteria was found in all the
      experimental groups. There was less bacterial extrusion in K3 Group while more
      bacterial extrusion was seen in Mtwo Group.

PMID- 23956530
TI  - Sealing ability of mineral trioxide aggregate, calcium phosphate and
      polymethylmethacrylate bone cements on root ends prepared using an Erbium:
      Yttriumaluminium garnet laser and ultrasonics evaluated by confocal laser
      scanning microscopy.
AB  - BACKGROUND: Surgical endodontic therapy comprises of exposure of the involved
      root apex, resection of the apical end of the root, preparation of a class I
      cavity, and insertion of a root end filling material. Mineral trioxide aggregate
      (MTA) is now the gold standard among all root end filling materials. MTA is
      however difficult to handle, expensive and has a very slow setting reaction. AIM:
      (1) To compare the sealing ability of MTA, polymethylmethacrylate (PMMA) bone
      cement and CHITRA Calcium phosphate cement (CPC) when used as root end filling
      material using Rhodamine B dye evaluated under a confocal laser scanning
      microscope. (2) To compare the seal of root ends prepared using an ultrasonic
      retroprep tip and an Er: YAG laser using three different root end filling
      materials. STATISTICAL ANALYSIS: Statistical analysis was performed using a one
      way ANOVA and a two-way ANOVA, independent samples t-test and Scheffe's post hoc
      test using SPSS Version 16 for Windows. RESULTS: All the three materials, namely
      MTA, PMMA BONE CEMENT and CHITRA CPC, showed microleakage. Comparison of
      microleakage showed maximum peak value of 0.86 mm for MTA, 0.24 mm for PMMA bone
      cement and 1.37 mm for CHITRA CPC. The amount of dye penetration was found to be
      lesser in root ends prepared using Er: YAG laser when compared with ultrasonics,
      but the difference was found to be not statistically significant. CONCLUSION:
      PMMA bone cement is a better material as root end filling material to prevent
      apical microleakage. MTA still continues to be a gold standard root end filling
      material showing minimum microleakage. Er: YAG laser is a better alternative to
      ultrasonics for root end preparations.

PMID- 23956531
TI  - Profilometric analysis of two composite resins' surface repolished after tooth
      brush abrasion with three polishing systems.
AB  - AIM: To evaluate the effect of three polishing protocols that could be
      implemented at recall on the surface roughness of two direct esthetic restorative
      materials. MATERIALS AND METHODS: Specimens (n = 40) measuring 8 mm (length) * 5
      mm (width) * 4 mm (height) were fabricated in an acrylic mold using two light
      cured resin-based materials (microfilled composite and microhybrid composite).
      After photopolymerization, all specimens were finished and polished with one of
      three polishing protocols (Enhance, One Gloss, and Sof-Lex polishing systems).
      The average surface roughness of each treated specimen was determined using 3D
      optical profilometer. Next all specimens were brushed 60,000 times with nylon
      bristles at 7200 rpm using crosshead brushing device with equal parts of
      toothpaste and water used as abrasive medium. The surface roughness of each
      specimen was measured after brushing followed by repolishing with one of three
      polishing protocols, and then, the final surface roughness values were
      determined. RESULTS: The data were analyzed using one-way and two-factor analysis
      of variance (ANOVA) and Tukey's honestly significant difference (HSD).
      Significant difference (P < 0.05) in surface roughness was observed. Simulated
      brushing following initial polishing procedure significantly roughened the
      surface of restorative material (P < 0.05). CONCLUSION: Polishing protocols can
      be used to restore a smooth surface on esthetic restorative materials following
      simulated tooth brushing.

PMID- 23956532
TI  - A survey of attitude and opinions of endodontic residents towards regenerative
      endodontics.
AB  - AIM: The objective of this survey was to study the level of awareness, current
      state of knowledge and opinions towards regenerative endodontic treatments
      amongst the endodontic residents of India. SETTINGS AND DESIGN: Questionnaire
      based survey was designed. MATERIALS AND METHODS: After approval from the
      organizing committee of 26(th) Federation of Operative Dentistry of India and
      19(th) Indian Endodontic Society National conference 2011, 200 copies of the
      questionnaire were circulated amongst the endodontic residents in conservative
      dentistry and endodontics at various colleges across the country about
      regenerative endodontic procedures. The survey included profile of the
      respondents and consisted of 23 questions about their knowledge, attitude and
      opinions regarding use of these procedures as part of future dental treatment.
      RESULTS: The survey showed that half the participants (50.6%) had received
      continued education in stem cells and/or regenerative dental treatments. The
      majority of participants were of the opinion (86.6%) that regenerative therapy
      should be incorporated into dentistry, and most of them (88%) were willing to
      acquire training in learning this new treatment strategy. The results indicated
      that half of the participants (52.6%) were already using some type of
      regenerative therapy in their clinical practice; however, with a majority of
      these limited to use of membranes, scaffolds or bioactive materials. CONCLUSIONS:
      These results reflect that endodontic residents are optimistic about the use of
      regenerative endodontic procedures; however, a need for more research and
      training was felt.

PMID- 23956533
TI  - Antibacterial effects of hybrid tooth colored restorative materials against
      Streptococcus mutans: An in vitro analysis.
AB  - OBJECTIVE: The objective of this study was to evaluate the antibacterial effect
      of two hybrid restoratives, namely resin modified glass ionomer cement (GC Fuji
      IITM LC, GC Corporation, Tokyo, Japan) and giomer (Beautifil-II, Shofu Inc.,
      Kyoto, Japan) against Streptococcus mutans [Microbial Type Culture Collection
      (MTCC), 890]. MATERIALS AND METHODS: The antibacterial effect was evaluated using
      an agar diffusion test. The prepared wells in petri dishes were completely filled
      with chlorhexidine (positive control group), resin modified glass ionomer cement
      and giomer respectively. Prepared bacterial suspension was poured over the petri
      dish and was spread evenly using the plate spreader. The culture plates were
      placed in the incubator for 24 h at 37 degrees C. The antibacterial activity was
      evaluated after 24 h, 48 h, and 7 days for each group in triplicates. RESULTS AND
      CONCLUSION: The results of the antibacterial effect of the tested materials were
      collected, statistically analyzed using the ANOVA test to determine the
      difference between the mean diameters of the inhibition zone produced. The mean
      zone of bacterial inhibition was found to be more with the giomer specimens at
      all time periods. However, this inhibitory activity showed a gradual decrease
      over a period of 7 days and the maximum inhibition was evident after 24 h with
      both the test materials.

PMID- 23956534
TI  - Comparative evaluation of the effects of multiple autoclaving on cyclic fatigue
      resistance of three different rotary Ni-Ti instruments: An in vitro study.
AB  - AIMS: The aim of this in vitro study was to evaluate comparatively the effects of
      multiple autoclaving on surface topography and cyclic fatigue of three different
      rotary nickel-titanium (Ni-Ti) instruments. MATERIALS AND METHODS: Twenty-one
      files each of Twisted Files (TF), Revo-S, and RaCe were used in this study. They
      were grouped as group 1-TF, group 2-Revo-S, and group 3-RaCe. All the files were
      autoclaved and subjected for scanning electron microscopic analysis and cyclic
      fatigue analysis. RESULTS: Data were subjected to statistical analysis using one
      way analysis of variance (ANOVA) and post hoc Tukey's Kramer multiple comparison
      test. TF exhibited the highest cyclic fatigue resistance followed by Revo-S and
      RaCe. Scanning electron photomicrographs showed no obvious surface changes in the
      files after three autoclaving cycles. CONCLUSIONS: Within the limitation of this
      study, it can be concluded that Twisted Files was the most fatigue resistant
      compared to Revo-S and RaCe, and multiple autoclaving cycles did not have any
      significant alterations in the cyclic fatigue resistance of rotary Ni-Ti files.

PMID- 23956535
TI  - Comparative antimicrobial efficacy of Metapex, Metronidazole, BioPure MTAD,
      Aztreonam on Bacteroides fragilis and Propionibacterium acne.
AB  - AIM: The purpose of this study was to evaluate the comparative antibacterial
      efficacy of Biopure MTAD, Metapex, Metronidazole, and Aztreonam against two
      obligate anerobic bacteria. MATERIALS AND METHODS: Antimicrobial efficacy of
      selected medicaments against two obligate anaerobic bacteria Bacteroides fragilis
      and Propionibacterium acnes was done by Agar disc-diffusion method. Pre
      sterilized Whatman paper discs, 6 mm in diameter and soaked with the test
      solution, were prepared and placed onto the previously seeded agar Petri plates.
      Each plate was incubated in anaerobic jar for anerobic environment at 37 degrees
      C for 48 hours. A zone of inhibition was recorded for each plate and the results
      were analysed statistically. Saline and ethanol used as control group in this
      study. RESULTS: Biopure MTAD, Metapex and Metronidazole were effective against
      all the selected microorganisms. Aztreonam was effective against Bacteroides
      fragilis. Saline and ethanol used as control were ineffective. CONCLUSIONS:
      Metronidazole showed the superior antibacterial property amongst the tested
      medicaments.

PMID- 23956536
TI  - Physical properties and cytotoxicity comparison of experimental gypsum-based
      biomaterials with two current dental cement materials on L929 fibroblast cells.
AB  - AIM: To evaluate physical properties and cytotoxicity of pure gypsum-based (pure
      GYP) and experimental gypsum-based biomaterials mixed with polyacrylic acid (Gyp
      PA). The results were compared with calcium hydroxide (CH) and glass ionomer
      cement (GIC) for application as base/liner materials. MATERIALS AND METHODS:
      Vicat's needle was used to measure the setting time and solubility (%) was
      determined by percentage of weight loss of the materials following immersion in
      distilled water. For cytotoxicity test, eluates of different concentrations of
      materials were obtained and pipetted onto L-929 mouse fibroblast cultures and
      incubated for 3 days. Cellular viability was assessed using Dimethylthiazol
      diphenyltetrazolium bromide test to determine the cytotoxicity level. Statistical
      significance was determined by one-way analysis of variance followed by post hoc
      test (P < 0.05). RESULTS: Setting time was significantly higher for pure-GYP and
      Gyp-PA; solubility test showed a similar tendency (pure-Gyp > Gyp-PA > CH = GIC).
      The pure-Gyp was found as the least cytotoxic materials at different
      concentrations. At 100 mg/mL dilutions of materials in growth medium highest
      cytotoxicity was observed with CH group. CONCLUSION: Cytotoxic effect was not
      observed with pure-Gyp; application of this novel biomaterial on deeper dentin/an
      exposed pulp and possibility of gradual replacement of this biodegradable
      material by dentin like structure would be highly promising.

PMID- 23956537
TI  - Comparative evaluation of the efficacy of different irrigants including MTAD
      under SEM.
AB  - CONTEXT: During biomechanical preparation, a smear layer is formed which occludes
      the openings of dentinal tubules and disfavors the penetration of irrigants.
      Hence, such layers should be removed. It becomes more challenging when we
      approach the apical third of the root canal. AIM: The aim was to compare the
      efficacy of different irrigants including ethylenediaminetetraacetic acid (EDTA),
      EDTA along with ultrasonication, citric acid, and mixture of tetracycline isomer,
      an acid, and a detergent (MTAD) as final irrigants where sodium hypochlorite
      (NaOCl) was used in each experimental group during root canal preparation with
      special emphasis on the apical third. SETTINGS AND DESIGN: Forty-five human upper
      anterior teeth were selected and divided into one control group (group 1) and
      four experimental groups (group 2 to group 5), each containing nine teeth. All
      the four experimental groups were irrigated with 5.25% NaOCl solution during
      preparation, whereas test irrigants (5 mL) as the final solution used in each
      experimental group were 17% EDTA, 17% EDTA along with ultrasonication, 25% citric
      acid, and MTAD, respectively. The samples were prepared and observed under a
      scanning electron microscope (SEM). The photomicrographs were recorded and
      evaluated with a scoring system. STATISTICAL ANALYSIS USED: Data were analyzed
      using Kruskal-Wallis test and Dunn's test (P = 0.05). RESULTS: None of the
      combined irrigants was found completely effective. All the test irrigants
      including MTAD worked well in the middle and cervical third, whereas MTAD showed
      excellent results in the apical third as compared to the other groups.

PMID- 23956538
TI  - Role of casein phosphopeptide amorphous calcium phosphate in remineralization of
      white spot lesions and inhibition of Streptococcus mutans?
AB  - INTRODUCTION: To promote the remineralization by ionic exchange mechanism instead
      of invasive techniques many remineralizing agents can be used. OBJECTIVE: To
      evaluate the remineralization effects of casein phosphopeptide-amorphous calcium
      phosphate (CPP-ACP) on white spot lesions (WSLs) and its inhibitory effect on
      Streptococcus mutans colonization. MATERIALS AND METHODS: The study group
      consisted of 60 subjects exhibiting at least 1-WSL. Subjects were randomly
      divided into 2 groups: A test group using CPP-ACP cream (GC-Tooth Mousse, Leuven,
      Belgium) and a control group using only fluoride containing toothpaste for a
      period of 3-month. Baseline WSLs were scored using DIAGNOdent device (KaVo
      Germany) and the saliva samples were collected to measure S. mutans counts. After
      the 3-month period the WSLs were again recorded and the saliva collection was
      repeated. RESULT: DIAGNOdent measurements were increased by time (P = 0.002) in
      the control group and no statistically significant difference (P = 0.217) was
      found in the test group by the 3-month period. In both groups, the mutans counts
      were decreased in the 3-month experimental period. CONCLUSION: These clinical and
      laboratory results suggested that CPP-ACP containing cream had a slight
      remineralization effect on the WSL in the 3-month evaluation period however,
      longer observation is recommended to confirm whether the greater change in WSLs
      is maintained.

PMID- 23956539
TI  - Coronal discoloration effect of three endodontic sealers: An in vitro
      spectrophotometric analysis.
AB  - AIM: This in vitro study compared the coronal discoloration effect of three
      endodontic sealers at short-time intervals. MATERIALS AND METHODS: The crowns of
      50 extracted premolars were cut and their pulp chambers were cleaned and randomly
      divided into five groups (n = 10). The following materials were placed into the
      pulp chambers: Group I: AH Plus, group II: Apexit Plus, group III: Sultan, group
      IV: Amalgam, and group V: Distilled water. The color of the crowns was measured
      using ShadepilotTM spectrophotometer (DeguDent, Hanau, Germany) prior and after
      the placement of experimental materials within pulp chambers. Color changes
      (DeltaE values) and shades were recorded in 3, 10, and 17 days. A Kruskal-Wallis
      and Mann-Whitney tests were used to assess significant differences between the
      sealers. Wilcoxon test was used to compare color changes at different periods
      within each group. RESULTS: All sealers showed significant discoloration effect
      that increased over the time. At the end of the observation period, Apexit Plus
      showed the lowest coronal discoloration effect (DeltaE = 6.38 +/- 0.55).
      CONCLUSIONS: All sealers used in the current study may cause a progressive
      coronal discoloration effect over 10-17 days. Apexit Plus sealer showed the
      lowest coronal discoloration effect.

PMID- 23956540
TI  - Influence of various herbal irrigants as a final rinse on the adherence of
      Enterococcus faecalis by fluorescence confocal laser scanning microscope.
AB  - AIM: The aim of this study was to assess the antibacterial efficacy of three
      different herbal irrigants against Enterococcus faecalis. MATERIALS AND METHODS:
      Single rooted teeth were extracted due to orthodontic and periodontal reasons.
      The teeth were then inoculated with E. faecalis. The teeth were randomly divided
      into three experimental groups and two control groups of six samples each. Group
      1 specimens were treated with 5.2% sodium hypochlorite (NaOCL) for 30 min
      followed by 5 mmol/L Ethylenediaminetetraacetic acid (EDTA) for 5 min and saline
      as final irrigant. Group 2 specimens were treated with and 5.2% NaOCl for 30 min
      as final irrigant. Group 3 were treated with Morinda citrifolia (MC) for 30 min
      as final irrigant. Group 4 were treated with Azadiracta indica (AI) as final
      irrigant. Group 5 were treated with green tea (GT) for 30 min as final irrigant.
      The dentin specimens were carefully spread onto a microscope slide and stained
      with BacLight and examined in a confocal laser scanning microscope set to monitor
      fluorescein isothiocyanate and propidium iodide. A total of nine fields were
      examined for each treatment and the bacteria presented were counted. STATISTICAL
      ANALYSIS: Using the one-way ANOVA with multiple comparison, significantly less
      bacteria were found adhering to the samples treated with Neem followed by NaOCL,
      GT, MC, Saline. RESULTS: AI treatment produced the maximum reduction in adherence
      of E. faecalis to dentin (9.30%) followed by NaOCl (12.50%), GT (27.30%), MC
      (44.20%) and saline (86.70%). CONCLUSION: Neem is effective in preventing
      adhesion of E. faecalis to dentin.

PMID- 23956541
TI  - Effects of home bleaching on surface hardness and surface roughness of an
      experimental nanocomposite.
AB  - OBJECTIVE: Home bleaching agents may not be safe for composite resins. The
      purpose of this study was to evaluate the effects of 10 and 20% Opalescence((r))
      PF home bleaching agents on the surface roughness and hardness of universal
      nanocomposite (Filtek Z350), anterior nanocomposite (KeLFiL), and nanohybrid
      composite (TPH 3). MATERIALS AND METHODS: Fifty-four composite resin samples with
      18 samples for each type of composite resin were prepared using acrylic molds (4
      * 2 mm). Each type of composite resin was further divided into three groups [n =
      6 controls were placed in distilled water for 14 days and the other two groups of
      n = 6 were bleached with 10 and 20% carbamide peroxide (CP), respectively for 14
      days]. Surface hardness of the composite resin was tested with a Vickers hardness
      tester, whereas surface roughness was tested with atomic force microscopy (AFM).
      RESULTS: There were significant changes in the surface hardness of KeLFiL and TPH
      3. However, all the tested materials showed no significant changes in the surface
      roughness. CONCLUSION: After 14 days of home bleaching treatment, there was no
      adverse effect on the surface roughness of all three composite resins, although
      the surface hardness for KeLFiL and TPH 3 were significantly reduced.

PMID- 23956542
TI  - In vitro evaluation of the efficacy of laser fluorescence (DIAGNOdent) to detect
      demineralization and remineralization of smooth enamel lesions.
AB  - OBJECTIVE: Early detection of smooth surface lesions is important for appropriate
      management and monitoring of dental caries. The purpose of this in vitro study
      was to evaluate the efficacy of laser fluorescence to detect demineralization and
      remineralization of smooth enamel surfaces. MATERIALS AND METHODS: In this in
      vitro study, 132 enamel blocks of semi-impacted human third molars were obtained;
      artificial caries lesions were induced and they were submitted to the pH-cycling
      process to create remineralization. Superficial microhardness (SMH) and laser
      fluorescence (LF) analysis were performed at baseline, after demineralization,
      and remineralization processes. The data were analyzed by Statistical Package for
      Social Sciences (SPSS)-16 using analysis of variance (ANOVA), Paired samples t
      test, and Pearson's correlation test. RESULTS: There was a significant difference
      between SMH values at baseline, after demineralization and after
      remineralization. Also, a statistically significant difference was observed
      between LF values in these three stages. The LF values increased after
      demineralization and then decreased after remineralization, and the SMH values
      decreased after demineralization and increased after remineralization. There was
      an inverse relationship between SMH and LF only at baseline and after
      demineralization, but not after remineralization. CONCLUSION: The results showed
      that LF is an appropriate method for detection of demineralization in an in vitro
      condition in smooth enamel lesions, but it was not so efficient in the detection
      of remineralization.

PMID- 23956543
TI  - Long-term bonding effectiveness of simplified etch-and-rinse adhesives to dentin
      after different surface pre-treatments.
AB  - OBJECTIVE: To evaluate the effect of 2% chlorhexidine (CHX) and 30%
      proanthocyanidin (PA) application on the immediate and long-term bond strength of
      simplified etch-and-rinse adhesives to dentin. MATERIALS AND METHODS: One hundred
      twenty extracted human molar teeth were ground to expose the flat dentin surface.
      The teeth were equally divided into six groups according to the adhesives used,
      either Tetric N Bond or Solobond M and pretreatments given either none, CHX, or
      PA. Composite cylinder was bonded to each specimen using the respective adhesive
      technique. Half the samples from each group (n = 10) were then tested
      immediately. The remaining samples were tested after 6 month storage in distilled
      water. RESULTS: The mean bond strength of samples was not significantly different
      upon immediate testing being in the range of 8.4(+/-0.7) MPa. The bond strength
      fell dramatically in the control specimens after 6 month storage to around 4.7(+/
      0.33) MPa, while the bond strength was maintained in the samples treated with
      both CHX and PA. CONCLUSION: Thirty percent PA was comparable to 2% CHX with
      respect to preservation of the resin dentin bond over 6 months.

PMID- 23956544
TI  - Comparative evaluation of microtensile bond strength of different solvent based
      one step and two step adhesive systems to dentin. An in-vitro study.
AB  - AIM AND OBJECTIVE: To compare and evaluate the micro tensile bond strength of
      different solvent based one step and two step adhesive systems to dentin.
      MATERIALS AND METHODS: Sixty recently extracted human mandibular premolars were
      subjected for the study and divided into 4 groups of fifteen each. The adhesive
      materials Single Bond, Prime and Bond XP, Clearfil S3 Bond and G-Bond were
      applied to flat dentin surfaces according to the manufacturer's instructions.
      After resin composite build up, teeth were sectioned to obtain beams with an
      approximate cross sectional area of 2 mm(2) and stressed to failure. Data were
      analysed statistically by ANOVA and student Neuman Keuls multiple comparison
      tests. RESULTS: The study demonstrated that Single Bond has better bond strength
      to dentin compared to the other adhesive systems. CONCLUSION: Ethanol and water
      based two-step adhesive Single Bond exhibited significantly higher microtensile
      bond strength values to dentin among all the adhesive systems tested.

PMID- 23956545
TI  - Evaluation to determine the caries remineralization potential of three
      dentifrices: An in vitro study.
AB  - AIM: The aim of this study was to evaluate the remineralizing potential of three
      different remineralizing agents (GC tooth Mousse, Clinpro tooth crthetame and SHY
      NM) on demineralized tooth surfaces using micro CT and microhardness. MATERIALS
      AND METHODS: Forty five freshly extracted mandibular premolars were collected and
      enamel specimens were prepared. The samples were assigned to three groups with
      fifteen specimens in each group. The specimens were then demineralized using
      McInne's demineralizing solution in two cycles. After that, remineralization was
      carried out in two cycles for 30 days using Casein phosphopeptide - Amorphous
      calcium phosphate (CPP - ACP), 0.21% sodium fluoride - Tricalcium phosphate (f
      TCP) and Calcium Sodium Phosphosilicate (CSP) containing tooth pastes for groups
      I, II, III respectively. The specimens were evaluated for Linear attenuation co
      efficient using micro CT (ScancoTM) and Vicker's Micro Hardness (SchimadzuTM)
      testing at different time periods. The results were tabulated and statistically
      analysed. RESULTS: It was observed that all the three remineralizing agents used
      in the study significantly increased the Linear Attenuation Co-efficient and
      Vicker's hardness number values of the enamel specimens following 15 days and 30
      days application. CONCLUSION: CPP - ACP showed the better remineralizing
      potential than the other two agents and there was no statistical significant
      difference between f-TCP and CSP groups.

PMID- 23956546
TI  - Endodontic management of a mandibular second premolar with perforating internal
      resorption by using MTA and cone beam computed tomography as a diagnostic aid.
AB  - This case report demonstrates the benefits of utilizing Cone Beam Computed
      tomography (CBCT) in the assessment and mineral trioxide aggregate (MTA) in the
      management of perforating internal resorption in a 54-year-old woman. The advent
      of CBCT has enhanced the clinician's ability to make a confirmatory diagnosis and
      determining the treatment plan before undertaking the actual treatment. Thorough
      cleaning and shaping of the root canal space and the resorptive defect was
      achieved by mechanical instrumentation, irrigation, and interim calcium hydroxide
      dressing. Following this obturation of the canal below, the resorptive defect was
      done with gutta percha using lateral and warm vertical condensation. The
      resorptive defect was filled with mineral trioxide aggregate. Follow-up intraoral
      periapical radiographs and CBCT scans at 6 months showed adequate repair of the
      resorption and periapical rarefaction and the tooth remained asymptomatic. 

PMID- 23956547
TI  - Type I canal configuration in a single rooted maxillary first molar diagnosed
      with an aid of cone beam computed tomographic technique: A rare case report.
AB  - Anatomic variations in maxillary molars are frequent. These deviations are also
      one of the major cause for endodontic treatment failure owing to inadequate
      cleaning, shaping and sealing of root canal system. Diagnosis of such aberrations
      using newer imaging techniques like cone beam computed tomography is firmly
      advocated. The present paper highlights the root canal treatment of a rare case
      of type I canal morphology diagnosed with an aid of cone beam computed
      tomographic technique. 

PMID- 23956548
TI  - 14(th) IACDE and IES PG Convention.

PMID- 23956549
TI  - Translational research: Basic science to health care. Way forward.

PMID- 23956550
TI  - Hot-water epilepsy: From bench to bedside.

PMID- 23956551
TI  - Sleep medicine: Evolution in India.

PMID- 23956552
TI  - Primary sleep disorders seen at a Neurology service-based sleep clinic in India:
      Patterns over an 8-year period.
AB  - There is an increasing awareness for recognition of sleep disorders in India;
      however, there is still a huge gap in the number of people suffering from various
      sleep disorders, in the community versus those visiting hospital clinics for the
      same. Ours is a neurology services-based sleep disorders clinic, which has
      evolved successfully over the last decade. In this study, we aimed to evaluate
      the changes in referral patterns and distribution of various sleep disorders in
      the patients presenting to the clinic. MATERIALS AND METHODS: This is a
      retrospective chart review-based study on all patients seen over an 8-year
      period, divided into 2 groups comprising of patients seen during the first 4
      years versus those seen over the next 4 years. Only those patients who had the
      sleep disorder as their presenting manifestation and those who had been formally
      interviewed with a pre-structured questionnaire detailing about the main features
      of the common sleep disorders according to the ICSD-R were included. Patients, in
      whom the sleep disorder could be clearly attributable to another neurological or
      systemic disorder, were excluded. Statistical analysis was carried out to
      identify the differences between the two groups as regards the distribution of
      various sleep disorders and other clinical data. RESULTS: Among 710 patients
      registered in the clinic, 469 were included for analysis and 222 patients formed
      group 1 while 247 formed group 2. The main differences observed were in the form
      of a clear increase in the percentage of patients with sleep-related breathing
      disorders, sleep-related movement disorder, and the hypersomnias on comparison of
      distribution over the first 4 years versus the last 4 years; while a clear
      decline was seen in the number of patients with insomnia and parasomnias. A 3
      fold increase was observed in the number of patients in whom polysomnography was
      obtained. CONCLUSION: The distribution of various sleep disorders as seen in a
      neurology service-based sleep clinic is demonstrated in this study. Increasing
      referrals for sleep-disordered breathing, restless legs syndrome, and fewer
      referrals for insomnia and parasomnias might reflect on changing physician and
      patient awareness in our community.

PMID- 23956553
TI  - Sleeping over a sleep disorder - Awareness of obstructive sleep apnoea as a
      modifiable risk factor for hypertension and stroke: A survey among health care
      professionals and medical students.
AB  - BACKGROUND: Obstructive sleep apnoea (OSA) syndrome is an established and
      modifiable but under recognized risk factor for common disorders like stroke and
      hypertension. OBJECTIVE: To assess awareness level of health care practitioners
      and medical students about OSA as a risk factor for stroke and hypertension.
      METHODS: Questionnaire based survey with multiple response type and fill in the
      blanks type questions. The data was compiled and analyzed using SPSS version 19.
      RESULTS: 180 participants completed the survey questionnaire. Only 24 (13.3%)
      identified OSA as a reversible risk factor for ischemic stroke. 11 (6%)
      participants only could answer OSA as an identified risk factor for hypertension
      as per Seventh Joint National Committee report. CONCLUSION: This study reveals
      dismal level of awareness, among health professionals and medical students, about
      OSA being an established and modifiable risk factor for hypertension and ischemic
      stroke.

PMID- 23956554
TI  - Rapid eye movement dependent central apnea with periodic leg movements.
AB  - Central sleep apnea is a period of at least 10 s without airflow, during which no
      ventilatory effort is present. Most of the central apneas occur in Non-Rapid eye
      movement (NREM) sleep. Central apnea occuring in Rapid eye movement (REM) sleep
      is extremely rare. We present our patient who had a diagnosis of obstructive
      sleep apnea in another sleep center since 2003. His Auto Continuous Positive
      Airway Pressure (CPAP) machine was disrupted so he admitted to our center to
      renew his machine and for daytime sleepiness while using his machine. The
      polysomnography revealed central apneas ending with respiratory arousals and
      periodic leg movements in rapid eye movement (REM) stage. We found no cause for
      central apneas. The patient benefited from servo ventilator therapy. We present
      this case as an unusual form of central apnea with the review of the literatures.
      Even the patients diagnosed as obstructive sleep apnea should be analyzed
      carefully. The diagnosis and the therapeutic approach may change in the favor of
      the patient. 

PMID- 23956555
TI  - Clinical profile of psychogenic non-epileptic seizures in adults: A study of 63
      cases.
AB  - AIMS: To evaluate clinical profile and short-term outcome of psychogenic non
      epileptic seizures (PNES) in Indian adult population. SETTING AND DESIGN: A
      prospective observational study, conducted at tertiary teaching institute at New
      Delhi. MATERIALS AND METHODS: Sixty-three patients with confirmed PNES were
      enrolled. The diagnosis was based on witnessing the event during video
      electroencephalography (Video-EEG) monitoring. A detailed clinical evaluation was
      done including evaluation for coexistent anxiety or depressive disorders.
      Patients were divided into two groups on the basis of excessive or paucity of
      movements during PNES attacks. Patients were followed-up to 12 months for their
      PNES frequency. STATISTICAL ANALYSIS: Means and standard deviations were
      calculated for continuous variables. Chi-square and Students t-test were used to
      compare categorical and continuous variables respectively. RESULTS: The mean age
      at onset of PNES was 25.44 years; with F:M ratio of 9.5:1. Coexistent epilepsy
      was present in 13 (20.63%) cases. Twenty-two patients (44%) with only PNES (n =
      50) had received antiepileptic drugs. Out of 63 patients of PNES 24 (38.1%) had
      predominant motor phenomenon, whereas 39 (61.9%) had limp attacks. The common
      features observed were pre-ictal headache, ictal eye closure, jaw clenching,
      resistant behavior, ictal weeping, ictal vocalization, and unresponsiveness
      during episodes. Comorbid anxiety and depressive disorders was seen in 62.3% and
      90.16% patients, respectively. Short-term (6-12 months) outcome of 45 patients
      was good (seizure freedom in 46.66% and >50% improvement in 24.44% cases).
      CONCLUSION: PNES is common, but frequently misdiagnosed and treated as epileptic
      seizures. A high index of suspicion is required for an early diagnosis. Proper
      disclosure of diagnosis and management of the psychiatric comorbidities can
      improve their outcome. LIMITATION: Limited sample size and change in seizures
      frequency as the only parameter for the assessment of the outcome are the two
      major limitations of our study.

PMID- 23956556
TI  - Idiopathic generalized epilepsy: Phenotypic and electroencephalographic
      observations in a large cohort from South India.
AB  - PURPOSE: We studied the phenotype and electroencephalographic (EEG) features, and
      therapeutic aspects of idiopathic generalized epilepsies (IGEs) in South Indian
      population. PATIENTS AND METHODS: This prospective cross-sectional hospital-based
      study was carried out on non-consecutive 287 patients (age 22.2 +/- 7.7 years;
      M:F = 139:148) with IGE syndrome. Their clinical and EEG observations were
      analyzed. RESULTS: Majority of the patients had onset of seizures <20 years of
      age (n = 178; 62%). Thirty one patients (10.8%) had family history of epilepsy.
      Nearly half of them (49.9%) had <5 years of duration of seizures. The type of
      IGEs included Juvenile myoclonic epilepsy (JME): 115 (40.1%); IGE with
      generalized tonic-clonic seizures (GTCS) only: 102 (39.02%); childhood absence
      epilepsy (CAE): 35 (12.2%); GTCS on awakening: 15 (5.2%); Juvenile absence
      epilepsy (JAE): 11 (3.8%); and unclassified seizures: 9 (3.1%). The triggering
      factors noted in 45% were sleep deprivation (20%), non-compliance and stress in
      5% each. The EEG (n = 280) showed epileptiform discharges in about 50% of
      patients. Epileptiform discharges during activation was observed in 40/249
      patients (16.1%): Hyperventilation in 32 (12.8%) and photic stimulation in 19
      (7.6%). The seizures were well controlled with anti-epileptic drugs (AEDs) in 232
      (80.8%) patients and among them, 225 (78.4%) patients were on monotherapy.
      Valproate (n = 131) was the most frequently prescribed as monotherapy.
      CONCLUSIONS: This is one of the largest cohort of patients with IGE. This study
      reiterates the importance of segregating IGE syndrome and such analysis will aid
      to the current understanding and management.

PMID- 23956557
TI  - Young girl with abnormal behavior: Anti-N-Methyl-D-Aspartate receptor immune
      encephalitis.
AB  - Anti N Methyl D Aspartate receptor immune encephalitis (Anti NMDARE) is a
      recently defined, under-recognized and often misdiagnosed disease, which
      typically occurs in young females and may be associated with an underlying tumor,
      usually ovarian teratoma. If diagnosed early, initiation of immunotherapy and
      tumor removal (if present) may result in recovery. We report a case of a 17 years
      old girl with Anti NMDARE who was initially misdiagnosed as Functional psychosis,
      Neuroleptic Malignant Syndrome and Sepsis syndrome. To the best of our knowledge,
      this is only the second case of anti NMDARE being reported from India. This case
      report underscores the need for a greater awareness of this entity across
      multiple specialties, e.g., general medicine, psychiatry and neurology, to ensure
      a heightened diagnostic suspicion, which can lead to timely diagnosis and
      adequate therapy of this treatable disease. 

PMID- 23956558
TI  - Fast micrographia: An unusual but distinctive sign.
AB  - Fast micrographia is a rare clinical sign, which is reported in patients with
      pallidal pathology. A 68-year-old male presented with hypophonia and short
      shuffling gait with decreased arm swing. About 3 weeks before, he had an acute
      myocardial infarction and a period of hemodynamic and respiratory distress during
      which he required mechanical ventilatory support. He was found to have a fast
      handwriting with micrographia from the outset. His rapid alternating hand and
      finger movements were normal. Magnetic resonance imaging (MRI) of the brain
      showed features of hypoxic ischemic encephalopathy including hyperintensities on
      T1 and T2 weighted images in the globus pallidus, and putamen bilaterally. 

PMID- 23956559
TI  - Transcranial doppler: Technique and common findings (Part 1).
AB  - Transcranial Doppler (TCD) can be aptly called as the doctor's stethoscope of the
      brain. Since its introduction in 1982, by Rune Aaslid, TCD has evolved as a
      diagnostic, monitoring, and therapeutic tool. During evaluation of patients with
      acute ischemic stroke, TCD combined with cervical duplex ultrasonography provides
      physiological information on the cerebral hemodynamics, which is often
      complementary to structural imaging. Currently, TCD is the only diagnostic tool
      that can provide real time information about cerebral hemodynamics and can detect
      embolization to the cerebral vessels. TCD is a noninvasive, cost-effective, and
      bedside tool for obtaining information regarding the collateral flow across
      various branches of the circle of Willis in patients with cerebrovascular
      disorders. Advanced applications of TCD help in the detection of right-to-left
      shunts, vasomotor reactivity, diagnosis, and monitoring of vasospasm in
      subarachnoid hemorrhage and as a supplementary test for confirmation of brain
      death. This article describes the basic ultrasound physics pertaining to TCD
      insonation methods, for detecting the flow in intracranial vessels in addition to
      the normal and abnormal spectral flow patterns. 

PMID- 23956560
TI  - Study to assess the effectiveness of modified constraint-induced movement therapy
      in stroke subjects: A randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to assess the effectiveness
      of modified constraint induced movement therapy (m-CIMT) in stroke subjects.
      MATERIALS AND METHODS: A total of forty sub-acute stroke subjects were randomly
      assigned to either a m-CIMT (n = 20) or in a control group (n = 20). The m-CIMT
      group (14 men, 6 women; mean age = 55.2 years) consisted of structured 2 h
      therapy sessions emphasizing affected arm use, occurring 5 times/week for 2
      weeks. A mitt was used to restrain the unaffected arm for 10 h/day for 2 week.
      The control group (11 men, 9 women; mean age = 56.4 years) consisted of
      conventional rehabilitation for time-matched exercise program. The outcome
      measures were evaluated at pre- and post-intervention by using the Wolf Motor
      Function Test (WMFT) and Fugl-Meyer assessment (FMA) of motor recovery after
      stroke. RESULTS: After intervention significant effects were observed in m-CIMT
      group on WMFT (pre-test and post-test score was 28.04 +/- 6.58, 13.59 +/- 2.86; P
      =0.003). Similarly on FMA (pre- and post-test score was 31.15 +/- 6.37, 55.7 +/-
      6.4; P = 0.00). CONCLUSION: There is a significant improvem ent in upper
      extremity function so it indicates that m-CIMT is effective in improving the
      motor function of the affected arm in stroke subjects. However, its long-term
      effect has not proved since there was no follow-up after intervention.

PMID- 23956561
TI  - Relation of glycated hemoglobin with carotid atherosclerosis in ischemic stroke
      patients: An observational study in Indian population.
AB  - CONTEXT: Glycated hemoglobin A1c(HbA1c) indicates long-term uncontrolled
      hyperglycemia in the body, which in diabetic patients leads to various vascular
      complications as a part of generalized atherosclerosis culminating ultimately
      into ischemic stroke. AIMS: Study aims to show the association between marker of
      uncontrolled long-term hyperglycemia HbA1c and marker of atherosclerosis (Carotid
      intima media thickness [CIMT] and carotid plaque) in ischemic stroke patients.
      SUBJECTS AND METHODS: Carotid sonography using high resolution 7.5 MHz sonography
      technique was done in each patient to find the occurrence of increased CIMT and
      presence of plaque according to Mannheim CIMT Consensus (2004-2006). Levels of
      HbA1c measured in blood in both diabetic and non-diabetic patients and a
      comparison made between them. Finally an association sought between HbA1c levels
      with CIMT and plaque. RESULTS: The average value of HbA1c of this cohort was 7.51
      +/- 1.75% with higher values in diabetic patients (9.29 +/- 1.73%). The patients
      with high CIMT (>0.8 mm) had higher values of HbA1c then that of normal CIMT
      patients and this was nearly significantly (P = 0.06). However, HbA1c levels of
      blood were significantly associated with stroke patients with presence of carotid
      arteries plaque (P = 0.008). CONCLUSIONS: Prediction of future risk and
      prevention strategies for ischemic stroke could be formulated by utilizing HbA1c
      levels in both diabetic and non-diabetic population.

PMID- 23956562
TI  - Spectrum of clinicoradiological findings in spinal cord infarction: Report of
      three cases and review of the literature.
AB  - Spinal cord infarction (SCI) often remains undiagnosed due to infrequent
      occurrence and lack of established diagnostic procedures. The unique pattern of
      blood supply explains the heterogeneity of clinical presentation. We present
      three cases of SCI to highlight the varied spectrum of clinicoradiological
      findings. The first patient had posterior spinal artery infarction, and spine
      imaging showed infarction of adjacent vertebral body, which is usually rare. The
      second patient had anterior spinal artery infarction and the cANCA titers were
      elevated. The third patient had a pure motor quadriparesis. Initial imaging did
      not show any cord infarction, but signal changes were noted on serial imaging.
      Fibrocartilagenous embolism (FCE) seems the most likely etiology in the first and
      third cases. A high index of clinical suspicion is necessary for prompt
      diagnosis. Sensitivity of the initial magnetic resonance imaging remains limited,
      necessitating serial follow-up scans. Infarction of the adjacent vertebral body
      is a useful confirmatory sign. Fat suppression images can delineate the marrow
      signal changes better. Elderly patients with vascular risk factors and
      degenerative discs need to avoid mechanical triggers that predispose to FCE.
      Younger patients with SCI will need evaluation for cardioembolic source and
      vasculitis. 

PMID- 23956563
TI  - Sedation in neurological intensive care unit.
AB  - Analgesia and sedation has been widely used in intensive care units where
      iatrogenic discomfort often complicates patient management. In neurological
      patients maximal comfort without diminishing patient responsiveness is desirable.
      In these patients successful management of sedation and analgesia incorporates a
      patient based approach that includes detection and management of predisposing and
      causative factors, including delirium, monitoring using sedation scales, proper
      medication selection, emphasis on analgesia based drugs and incorporation of
      protocols or algorithms. So, to optimize care clinician should be familiar with
      the pharmacokinetic and pharmacodynamic variables that can affect the safety and
      efficacy of analgesics and sedatives. 

PMID- 23956564
TI  - Clinical profile and outcome of myasthenic crisis in a tertiary care hospital: A
      prospective study.
AB  - BACKGROUND: The present understanding of the clinical course, complications, and
      outcome of myasthenic crisis (MC) is based chiefly on observational studies and
      retrospective case series. AIM: To study the baseline demographic and clinical
      variables, risk factors, complications, outcome, and mortality in patients of MC.
      MATERIALS AND METHODS: All patients of myasthenia gravis (MG) who presented with
      myasthenic crisis between July 2009 and December 2010 were included. RESULTS: Ten
      patients of MC were included in this study. The median age of the patients was
      40.5 years (range 14-71 years). Seven were females and three were males. Nine had
      generalized MG and one patient had oculobulbar involvement only. Median duration
      of disease was 3 years (range 1 month to17 years). Two patients had thymoma. Two
      patients had history of thymectomy in the past. Infection was the most common
      triggering factor accounting for five cases (50%) followed by inadequate
      treatment/drug withdrawal in three (30%) and steroid initiation and hypokalemia
      in the remaining two patients (20%). Median duration of MC was 12 days (range 3
      28 days). Mortality was in 3 out of 10 (30%) during MC. Management in the
      intensive care unit (ICU) and treatment with plasma exchange/intravenous
      immunoglobulins were associated with good outcome. CONCLUSIONS: Ventilator
      support and management in intensive care unit are the most important components
      in the management of MC. The high mortality rate seen in present study may be
      more reflective of the actual ground reality in resource constrained developing
      countries, however, larger prospective studies are needed to confirm these
      findings.

PMID- 23956565
TI  - Efficacy of terbutaline in familial limb girdle myasthenia: Case report and
      review of literature.
AB  - Congenital myasthenic syndromes (CMS) are frequently misdiagnosed due to their
      wide clinical heterogeneity. Molecular defects in various end-plate associated
      proteins are being identified. Better understanding of the molecular pathogenesis
      and genotype-phenotype correlations can help evolve newer therapeutic targets. We
      present a report of two siblings with familial limb girdle myasthenia who showed
      significant objective clinical improvement after initiation of terbutaline. The
      possible mechanism of action and utility of terbutaline in the setting of CMS are
      described. Terbutaline is a potential treatment option in certain subtypes of CMS
      refractory to conventional medicines. However, long-term follow-up is required to
      determine the overall efficacy and safety profile. 

PMID- 23956566
TI  - Clinical and biochemical spectrum of hypokalemic paralysis in North: East India.
AB  - BACKGROUND: Acute hypokalemic paralysis, characterized by acute flaccid paralysis
      is primarily a calcium channelopathy, but secondary causes like renal tubular
      acidosis (RTA), thyrotoxic periodic paralysis (TPP), primary hyperaldosteronism,
      Gitelman's syndrome are also frequent. OBJECTIVE: To study the etiology, varied
      presentations, and outcome after therapy of patients with hypokalemic paralysis.
      MATERIALS AND METHODS: All patients who presented with acute flaccid paralysis
      with hypokalemia from October 2009 to September 2011 were included in the study.
      A detailed physical examination and laboratory tests including serum
      electrolytes, serum creatine phosphokinase (CPK), urine analysis, arterial blood
      gas analysis, thyroid hormones estimation, and electrocardiogram were carried
      out. Patients were further investigated for any secondary causes and treated with
      potassium supplementation. RESULT: The study included 56 patients aged 15-92
      years (mean 36.76 +/- 13.72), including 15 female patients. Twenty-four patients
      had hypokalemic paralysis due to secondary cause, which included 4 with distal
      RTA, 4 with Gitelman syndrome, 3 with TPP, 2 each with hypothyroidism,
      gastroenteritis, and Liddle's syndrome, 1 primary hyperaldosteronism, 3 with
      alcoholism, and 1 with dengue fever. Two female patients were antinuclear
      antibody-positive. Eleven patient had atypical presentation (neck muscle weakness
      in 4, bladder involvement in 3, 1 each with finger drop and foot drop, tetany in
      1, and calf hypertrophy in 1), and 2 patient had respiratory paralysis. Five
      patients had positive family history of similar illness. All patients improved
      dramatically with potassium supplementation. CONCLUSION: A high percentage
      (42.9%) of secondary cause for hypokalemic paralysis warrants that the underlying
      cause must be adequately addressed to prevent the persistence or recurrence of
      paralysis.

PMID- 23956568
TI  - Thyrotoxic hypokalemic periodic paralysis as the presenting symptom of silent
      thyroiditis.
AB  - Silent thyroiditis is a rare cause of thyrotoxic periodic paralysis. The
      objective was to present a case of silent thyroiditis presenting as periodic
      paralysis. A 23-year-old man presented with recurrent acute flaccid predominantly
      proximal weakness of all four limbs. He had a similar episode 3 weeks back. On
      examination he was found to have hypokalemia secondary to thyrotoxicosis.
      Clinically there were no features of thyrotoxicosis or thyroiditis. He was
      initially treated with intravenous and later oral potassium supplementation and
      propranolol. At 8 weeks of follow-up his thyroid profile became normal and his
      propranolol was stopped. He had no further recurrence of paralysis. He was
      diagnosed as a case silent thyroiditis presenting as thyrotoxic periodic
      paralysis. In cases of recurrent or acute flaccid muscle paralysis, it is
      important to suspect thyrotoxicosis, even if asymptomatic. Definitive treatment
      of thyrotoxicosis prevents recurrence. 

PMID- 23956569
TI  - Prevalence and characteristics of migraine in medical students and its impact on
      their daily activities.
AB  - BACKGROUND: Migraine is a common neurological disorder with significant impact on
      quality of life. The aim of this study was to investigate the prevalence and
      characteristics of migraine headaches in medical students, to measure its impact
      on their life, and to assess their knowledge about the ailment. Information about
      lifestyle variables was also collected. MATERIALS AND METHODS: All medical
      students who confirmed of having headache for more than 1 year formed the study
      group. Students filled a detailed questionnaire focusing on demographics, pain
      characteristics, accompanying factors, triggers, and family history of migraine.
      Lifestyle variables were enquired and migraine associated disability was assessed
      by MIDAS (Migraine Disability Assessment). The diagnosis of migraine was made
      according to the International Headache Society criteria. Results are expressed
      in n = numbers and percentage. RESULTS: Sixty-eight percent of medical students
      had headache. The prevalence of migraine in the whole cohort was 28%; however, of
      the headache group, migraine constituted 42%. There was a female preponderance.
      One-fourth of the students had weekly or daily attacks with 31% students
      reporting increase in their headache intensity and frequency. Forty-four percent
      of students had severe headaches. Dizziness, allodynia, and neck stiffness were
      reported as accompanying symptoms. Trigger factors were identified in 99%
      students, predominant of which were poor sleep hygiene, environmental changes,
      head movements, and mental stress. Only 4% of students did regular exercise.
      Twenty-seven percent of students reported self-medication use of analgesics. One
      fourth of the students had migraine-associated disability but only 6% realized
      that they had migraine. CONCLUSION: Our study found a high prevalence of headache
      with migraine in medical students. The students' awareness of the disease was
      very low with one-fourth of the students resorting to self-medication. Our study
      identified previously less-recognized triggers like head movement and
      accompanying symptoms like neck stiffness. Migraine-attributed burden was high in
      medical students.

PMID- 23956570
TI  - Nummular headache and pituitary lesion: A case report and literature review.
AB  - Nummular headache (NH) is a newly categorized headache disorder characterized by
      a consistent clinicographics in each attack. Currently, it is considered as a
      primary headache disorder due to epicranial neuralgia but the pathomechanism is
      still unknown. We report a woman, whose recurrent NH subsided after trans
      sphenoidal surgery for her pituitary oncocytoma. The recovery of NH in this
      patient encourages the central mechanism for NH occurrence. After a review of
      literature concerning, NH and intracranial secondaries we propose that central NH
      is a referral pain from pain-sensitive structures, such as meninges,
      superimposing by pre-existing lower pain threshold or pain modulation. 

PMID- 23956571
TI  - Imaging signs in idiopathic intracranial hypertension: Are these signs seen in
      secondary intracranial hypertension too?
AB  - BACKGROUND: The purpose of this study was to evaluate the difference in the
      occurrence of the various "traditional" imaging signs of intracranial
      hypertension (IIH) on magnetic resonance imaging (MRI) in patients with
      idiopathic (IIH) and secondary intracranial hypertension. MATERIALS AND METHODS:
      In a retrospective analysis, the MRI findings of 21 patients with IIH and 60
      patients with secondary intracranial hypertension (41 with tumors; 19 with
      intracranial venous hypertension) were evaluated for the presence or absence of
      various "traditional" imaging signs of IIH (perioptic nerve sheath distention,
      vertical buckling of optic nerve, globe flattening, optic nerve head protrusion
      and empty sella) using the Fisher's exact test. Odds ratios were also calculated.
      Statistical Package for the Social Sciences version 17.0 was used for statistical
      analysis. Subgroup analysis of the IIH versus tumors and IIH versus venous
      hypertension were performed. RESULTS: Optic nerve head protrusion and globe
      flattening were significantly associated with IIH. There was no statistically
      significant difference in the occurrence of rest of the findings. On subgroup
      analysis, globe flattening and optic nerve head protrusion occurred significantly
      more often in IIH than in tumors. However, there was no statistically significant
      difference in the occurrence of any of these findings in patients with IIH and
      venous hypertension. CONCLUSIONS: IIH is a diagnosis of exclusion. While
      secondary causes of raised intracranial pressure (ICP) have obvious clinical
      findings on MRI, some conditions like cerebral venous thrombosis may have subtle
      signs and differentiating between primary and secondary causes may be difficult.
      In the absence of any evident cause of raised ICP, presence of optic nerve head
      protrusion or globe flattening can suggest the diagnosis of IIH.

PMID- 23956572
TI  - Sympathetic skin response in incomplete spinal cord injury with urinary
      incontinence.
AB  - OBJECTIVES: Sympathetic skin response (SSR) is a test for evaluation of the
      sympathetic sweat gland pathways, and it has been used to study the central
      sympathetic pathways in spinal cord injury (SCI). This study aimed to assess the
      autonomic pathways according to normal or abnormal SSR in urinary incontinence
      patients due to incomplete spinal cord injury. MATERIALS AND METHODS: Suprapubic,
      palmar, and plantar SSR to the peripheral nerve electrical stimulation were
      recorded in 16 urinary incontinence patients with incomplete spinal cord injury
      at various neurological levels and in 30 healthy control subjects. RESULTS: All
      the recordings of SSR from the incomplete SCI patients with urinary incontinence
      as compared with their counterparts in the control group showed significantly
      reduced amplitudes with more prominent reduction in the suprapubic area recording
      site (P value < 0.0004). SSR with significantly prolonged latencies were recorded
      from palm and plantar areas in response to suprapubic area and tibial N stimuli,
      respectively (P value < 0.02). In this study, a significantly higher stimulus
      intensity (P value < 0.01) was needed to elicit SSR in the cases compared with
      the control group. CONCLUSION: This study showed abnormal SSR in urinary
      incontinence patients due to incomplete SCI. In addition, for the first time we
      have described recording of abnormal SSR from the suprapubic area as another way
      to show bladder sympathetic system involvement.

PMID- 23956573
TI  - Joubert syndrome: Clinical and radiological characteristics of nine patients.
AB  - BACKGROUND: Joubert Syndrome (JS) is a rare genetic developmental disorder, first
      identified in 1969. In patients with JS, certain regions of the brain (mainly
      cerebellar vermis and brainstem) are underdeveloped or malformed. This can lead
      to impaired attention, visual, spatial, motor, language and social functional
      skills. JS is characterized by a host of features, many of which do not occur in
      every patient. AIM OF THE STUDY: To spotlight and increase awareness of clinical
      profile and neuroimaging findings of children with Joubert syndrome. METHODS:
      This is a retrospective case series study of patients with JS who attended the
      Pediatric Neurology Clinic in Aladan and Alfarawanya Hospitals in Kuwait, from
      September 2007 to September 2012. Clinical and radiological data were obtained
      from the patient medical records. RESULTS: Cerebellar vermis hypoplasia/aplasia
      and apnea were present in all patients, polydactly in 3 of 16, renal problems
      with cysts in 5 patients and 11 of 16 had abnormal electroretinograms (ERGs).
      Blood investigations of organic acids, amino acids and very-long-chain fatty
      acid, were normal in the all the nine patients. CONCLUSION: JS is a rare genetic
      brain malformation with association of retinal dystrophy and renal abnormalities.
      The retinal dystrophy may be progressive. The prognosis of patients depends
      mainly on the degree of brain malformation.

PMID- 23956574
TI  - Gas geyser syndrome: An important preventable cause of disabling neurological
      events.
AB  - To bring to light the greatly hazardous effects of the use of flue less gas
      geysers in the domestic setting. Over a period of two years (2008 to 2010) twenty
      six cases were documented as presenting with unexplained neurological events
      while bathing in an ill ventilated bathroom with a functional flue less gas
      geyser. The cases were mainly of three distinct prototypes namely seizure like
      episodes seen in 11 patients, carbon monoxide intoxication in 13 patients with
      near cardiac arrest in 4, and as a precipitating factor for epilepsy as seen in 2
      cases. Out of the 13 cases presenting as carbon monoxide intoxication 4 had
      subtle cognitive defects and 2 developed early Parkinsonian features on follow
      up. To increase awareness regarding gas geyser induced epilepsy and associated
      carbon monoxide intoxication, both of which are entirely preventable conditions.
      We also wish to emphasize the importance of stringent and universal
      implementation of gas geyser usage and installation laws. 

PMID- 23956575
TI  - A rare presentation of methanol toxicity.
AB  - Methanol is a highly toxic alcohol resembling ethanol in smell and taste.
      Methanol poisoning is a lethal form of poisoning that can cause severe metabolic
      acidosis, visual disturbances, and neurological deficit. Brain lesions typically
      described in methanol toxicity are in the form of hemorrhagic and non-hemorrhagic
      necrosis of the basal ganglia and sub-cortical white matter. To our knowledge,
      lesions in the parietal, temporal, or frontal areas of cerebrum and cerebellar
      hemispheres have been rarely reported so far. We herewith report this rare
      presentation. 

PMID- 23956576
TI  - Clinical and radiological findings in chlorfenapyr poisoning.
AB  - This is a case report of suicidal ingestion of chlorfenapyr, presenting with
      neurological complications after a latent period of more than a week, and rapidly
      progressing to death within days of symptoms. Chlorfenapyr is a moderately
      hazardous pesticide according to World Health Organization toxicity
      classification, and kills target organism by depriving it of energy through
      interference with oxidative phosphorylation at mitochondrial level. A pro
      pesticide, chlorfenapyr takes time to convert to its active form and either this
      active form or a toxic metabolite causes delayed neurological symptoms. It causes
      significant neurotoxicity in rat models. This case report provides for the first
      time from India (second worldwide), clinical and "radiological evidence"
      (magnetic resonance imaging showing demyelinating/oedematous changes) of
      "chlorfenapyr neurotoxicity in humans." It also highlights the "latent period"
      between ingestion and onset of fatal manifestations. Earlier, similar case
      reports of human deaths with delayed onset neurological symptoms, due to
      chlorfenapyr poisoning have been reported, from Japan, Columbia, and Korea. 

PMID- 23956577
TI  - Spinal MR imaging in Vitamin B12 deficiency: Case series; differential diagnosis
      of symmetrical posterior spinal cord lesions.
AB  - We report three cases of Vitamin B12 deficiency with symmetrical posterior spinal
      cord lesions and discuss the differential diagnosis, some of which are not well
      known. Because the degree of resolution of the clinical symptoms in subacute
      combined degeneration depends on early detection, MRI findings should not be
      missed. 

PMID- 23956579
TI  - Vogt-Koyanagi-Harada syndrome presenting with encephalopathy.
AB  - VogtKoyanagi-Harada (VKH) is a rare syndrome affecting tissues with melanocytes.
      The possibility that VKH syndrome has an autoimmune pathogenesis is supported by
      the high frequency of human leukocyte antigen-DR4 commonly associated with other
      autoimmune diseases. Eyes are the main affected organ, resulting in blindness.
      Brain disease as a late onset event is extremely rare. Here, we are reporting a
      57-year-old woman with previously diagnosed VKH syndrome, presenting with a late
      onset brain encephalopathy. She was treated with corticosteroids and discharged
      from hospital with good general condition. 

PMID- 23956578
TI  - Lemierre's Syndrome presenting with neurological and pulmonary symptoms: Case
      report and review of the literature.
AB  - Lemierre's Syndrome (LS) is a potentially life-threatening condition,
      characterized by clinical or radiologic evidence of internal jugular vein
      thrombosis following an oropharyngeal infection, most commonly by Fusobacterium
      necrophorum. A high index of suspicion and early recognition is important for
      successful management and to prevent systemic complications like multiorgan
      failure with extremely high morbidity, prolonged hospitalization and, not
      uncommonly, death. We are reporting a rare case of LS that was complicated with
      internal jugular vein and cavernous sinus thrombosis along with lung metastatic
      lesions, which was diagnosed and treated at our institute. 

PMID- 23956580
TI  - A case of late-onset allgrove syndrome presenting with predominant autonomic
      dysfunction.
AB  - Allgrove Syndrome or triple A syndrome is a rare familial multisystem disorder
      characterized by achalasia, alacrima and adrenal insufficiency. The objective was
      to describe a case of 4A syndrome where autonomic dysfunction was the presenting
      feature. A 22-year-old male presented with erectile dysfunction and loss of
      spontaneous morning erections for six months. He was having nocturnal diarrhea
      and recurrent postural dizziness for three months. He was found to have
      hyperpigmentation at pressure points, postural hypotension and other features of
      autonomic dysfunction. Laboratory investigations and imaging studies revealed
      hypoadrenalism, achalasia, alacrima and peripheral neuropathy. Autonomic
      neuropathy-related features persisted even after correction of hypoadrenalism.
      Based on clinical features and investigation he was diagnosed as a case of 4A
      syndrome presenting with autonomic dysfunction. Allgrove or 4A syndrome should be
      considered as a rare differential diagnosis of someone presenting with features
      of autonomic neuropathy. 

PMID- 23956581
TI  - Progressive ataxia associated with ocular apraxia type 1 (AOA1) with a presence
      of a novel mutation on the aprataxin gene.
AB  - Ataxia, although rare, can be a symptom of many debilitating movement disorders.
      Hereditary ataxias are one subset of this condition and manifest when there is a
      genetic abnormality involved. Ataxia oculomotor apraxia type 1 (AOA1), an
      autosomal recessive ataxia, results from a mutation on the aprataxin gene (APTX).
      We characterized a novel homozygous deletion mutation (IVS4-12delT) on the APTX
      gene in a 14-year-old male born to consanguineous parents. This case report
      emphasizes the importance of investigating and increasing awareness of novel
      genetic mutations in order to help diagnose and further classify hereditary
      ataxias. 

PMID- 23956582
TI  - Cystic cochleovestibular anomaly presenting with congenital deafness and
      recurrent bacterial meningitis in childhood.
AB  - Recurrent bacterial meningitis (RBM) in many instances is associated with
      identifiable anatomical defects. Presence of congenital deafness with recurrent
      meningitis should alert clinician for presence of middle and inner ear
      malformation. These defects can be demonstrated by various neuro imaging
      techniques and can be surgically corrected. In this case report we describe a
      child seen at our institute with congenital deafness and recurrent meningitis,
      discuss the approach to RBM and briefly describe inner ear malformation
      associated with the same and how to differentiate them. 

PMID- 23956583
TI  - Familial orthostatic tremor and essential tremor in two young brothers: A rare
      entity.
AB  - Orthostatic tremor (OT), is usually a disease of old age and is characterized by
      quivering movements of the legs during quiet standing or in the state of
      isometric contraction in the lower limbs. This is relieved on walking or on lying
      down. It is diagnosed by surface electromyography, particularly over the
      quadriceps femoris muscles which shows a distinctive frequency of 13 to 18 Hz on
      standing. Some investigators consider it as a variant of essential tremor (ET)
      and the two conditions often co-exist. The disease is usually non-familial. Two
      brothers presented with tremor in the lower limbs on standing and on the
      outstretched hands without any family history. Subsequently, they were proved to
      be suffering from OT and ET by clinical examination and surface EMG. Simultaneous
      occurrence of OT and ET in two young brothers without any family history in the
      previous generation has not been described before and they also appeared at a
      much earlier age than what is described in the literature. 

PMID- 23956584
TI  - Unusually prominent horizontal gaze palsy in a case of Niemann-Pick type C
      disease.
AB  - Niemann-Pick Type C disease (NPC) is a rare inherited metabolic disorder
      characterized by lipid accumulation and systemic manifestations due to multiple
      organ involvement. Only a few cases of NPC have been reported so far from India.
      Varying presentations and often lack of access to complex diagnostic tests have
      leaded to initial misdiagnosis on few occasions. We here report a provisionally
      diagnosed case of NPC with prominent horizontal gaze palsy along with
      characteristic vertical gaze palsy and normal findings on microscopic examination
      of skin biopsy specimen. 

PMID- 23956585
TI  - Late infantile neuronal ceroid lipofuscinosis: A case report with review of
      literature.
AB  - Neuronal ceroid lipofuscinosis (NCL) are a group of genetically mediated
      neurodegenerative disorders affecting children and young adults. They are
      characterized by global mental and motor deterioration, vision loss, and epilepsy
      ultimately resulting in death. Of the various types, late infantile variety is
      the 2(nd) most common form of NCL. Here the authors report a case of a 9-year-old
      boy who presented with progressive mental and social deterioration since the age
      of 21/2 years. As the disease progressed, he developed progressive vision loss,
      gait ataxia, action myoclonus, and epilepsy. Electroencephalogram revealed
      generalized sharp and slow wave discharges with background slowing. Magnetic
      resonance imaging of the brain revealed diffuse cerebral and cerebellar atrophy
      markedly affecting the cerebellum along with periventricular T2 hyperintensities.
      Skin biopsy from axilla revealed characteristic intracytoplasmic eosinophilic
      inclusions and periodic acid Schiff positive bodies within the eccrine ducts
      suggestive of NCL. 

PMID- 23956586
TI  - Intracranial neurenteric cyst: A rare cause of chemical meningitis.
AB  - Intracranial neurenteric cysts are exceedingly rare congenital intracranial
      lesions that result from disorder of gastrulation. Still, more rarely, the cyst
      contents may leak into the CSF and give rise to recurrent episodes of chemical
      meningitis. We present a case of chemical meningitis due to a leaking posterior
      fossa neurenteric cyst in a young female, with emphasis on its imaging features.
      The final diagnosis was achieved by sufficiently characteristic imaging features;
      histopathologic documentation could not be achieved as the patient denied
      surgery. 

PMID- 23956587
TI  - Varadi Papp syndrome, an unusual variant of oral-facial-digital syndrome: Report
      of a rare case.
AB  - Varadi Papp syndrome or oral-facial-digital syndrome type VI (OFDS VI) is a rare
      autosomal-recessive disorder distinguished from other OFDSs by metacarpal
      abnormalities with central polydactyly and by cerebellar abnormalities. Our
      patient had a broad forehead, arched eyebrows, left-sided squint, hypertelorism,
      epicanthic folds, fleshy nodular tongue, midline upper lip cleft, high arched
      palate, both pre-axial and post-axial polydactyly of limbs, hypotonia and
      cerebellar hypoplasia with molar tooth sign consistent with the diagnosis of
      Varadi Papp syndrome. 

PMID- 23956588
TI  - Demyelination presenting as tics in a healthy child.

PMID- 23956589
TI  - Two conjoined plaques or a flap?

PMID- 23956590
TI  - Apexification with calcium hydroxide and mineral trioxide aggregate: Report of
      two cases.
AB  - The completion of root development and closure of the apex occurs up to 3 years
      after the eruption of the tooth. The treatment of pulpal injury during this
      period provides a significant challenge for the clinician. The importance of
      careful case assessment and accurate pulpal diagnosis in the treatment of
      immature teeth with pulpal injury cannot be overemphasized. The treatment of
      choice for necrotic teeth is apexification, which is induction of apical closure
      to produce more favorable conditions for conventional root canal filling. The
      most commonly advocated medicament is calcium hydroxide, although recently
      considerable interest has been expressed in the use of mineral trioxide aggregate
      (MTA). We report a case series wherein calcium hydroxide and MTA were used
      successfully for one step apexification in teeth with open apex. 

PMID- 23956591
TI  - An infected dentigerous cyst associated with an impacted permanent maxillary
      canine, inverted mesiodens and impacted supernumerary teeth.
AB  - A dentigerous cyst is an odontogenic cyst associated with the crown of the
      impacted or unerupted teeth. Such cyst remain initially completely asymptomatic
      unless when infected and can be discovered only on routine radiographic
      examination. Here, such a case of dentigerous cyst, which was discovered on
      routine radiographic examination, is discussed here. 

PMID- 23956592
TI  - Hyperplasia of the mandibular body: An anomaly in a developmental anomaly.
AB  - Hyperplasias of the mandible are usually seen in relation to the condyle or
      affecting one half of the mandible, such cases being described as hemimandibular
      hyperplasia or elongation. This article presents a rare case of hyperplasia of
      the right body of the mandible. The case being unique in that although being
      present from childhood did not cause any functional disturbances or any occlusal
      disharmony characteristically seen in such developmental anomalies. Here, we
      describe the clinical, radiographic and histopathologic findings that led to the
      diagnosis hyperplasia of the mandibular body and the treatment rendered to
      provide the esthetic correction. 

PMID- 23956593
TI  - Rare form of cherubism: Case report with review of literature.
AB  - Cherubism was first described by Jones in 1933 as "familial multilocular cystic
      disease of jaws." Renamed as cherubism in 1938 because of classical
      characteristics of full round cheeks and upward cast of the eyes to the angelic
      look of the cherubs immortalized by renaissance art. It is characterized by
      progressive painless bilateral swelling of jaws involving either maxilla or
      mandible producing chubby face. It is uncommon fibro-osseous disorder of bone.
      Mutation in the gene encoding SH3-binding protein 2 (SH3BP2) plays a role in the
      disease. There are indications that the gene SH3BP2 plays a role in regulating
      the increased osteoblast and osteoclast activities that are seen in normal tooth
      eruption and point mutations in the gene could cause pathologic activation of
      osteoclasts. The purpose of this paper is to present the uncommon form of
      cherubism and to review the clinicoradiographic, histopathologic features and
      treatment so as to facilitate diagnosis of disease. 

PMID- 23956594
TI  - Immediate placement of dental implants in the mandible.
AB  - This case describes extraction of teeth in the mandibular arch, i.e., 41 42 43 44
      45 51 52 53 54 55 56 57 58 (grade two mobility), followed by immediate placement
      of four dental implants (3i biomet), two in the 45 55 region and two dental
      implants in 12 21 region. A prefabricated provisional mandibular denture was
      immediately placed. The purpose of immediate placement was to aid the patient
      resume his professional duties the next day itself along with esthetic and
      functional comfort, psychological well-being and most importantly preserving the
      remaining tissue in a healthy condition. 

PMID- 23956595
TI  - Ectodermal dysplasia in identical twins.
AB  - Hereditary hypohidrotic ectodermal dysplasia (HED) is typically inherited as an X
      linked recessive trait, characterized by deformity of at least two or more of the
      ectodermal structures - hair, teeth, nails and sweat glands. Two cases of
      hereditary HED involving identical male twins, is being documented for the rarity
      of its occurrence with special attention given to genetics, pathophysiology,
      clinical, intraoral manifestations and to the methods to improve the masticatory
      function, the facial esthetics and psychology of patients affected by this
      disease. 

PMID- 23956596
TI  - Scalpel versus electrosurgery: Comparison of gingival perfusion status using
      ultrasound Doppler flowmetry.
AB  - The main prerequisites of any surgical procedure are achievement of good
      visibility and access to the site with minimal bleeding and rapid and painless
      healing. With the advancement of technology the armamentarium for oral surgical
      procedures has also widened. The use of alternate methods to the traditional
      scalpel such as electrosurgery, laser, and chemicals has been widely experimented
      with. This article aims to report the gingival perfusion pre-operatively and post
      operatively, comparing the use of scalpel and electrosurgery in different
      anatomic sites in patient. Since wound healing is influenced by its
      revascularization rate, which follows the pattern of new connective tissue
      formation, the perfusion status of the gingiva has been studied using ultrasound
      spectral Doppler. The results of our study show that there was 30% more blood
      flow by 7(th) day, 19% more blood flow by 15(th) day and 11% more blood flow by
      30(th) day in sites where the scalpel was used compared with sites where
      electrosurgery technique was used. 

PMID- 23956597
TI  - Early rehabilitation of facial defects using interim removable prostheses: A
      clinical case report.
AB  - Surgical resection of neoplasms or malformations of the face may result in
      defects that are not amenable to immediate surgical reconstruction. Such defects
      can have a severe adverse effect on patient perceptions of body image and self
      esteem. In these cases, the use of an interim removable facial prosthesis can
      offer a rapid alternative treatment solution. The patient may then resume social
      interactions more comfortably while permitting easy access to the facial defect
      to observe tissue healing while awaiting definitive rehabilitation. This article
      presents a case report describing the use of interim nasal prostheses to provide
      rapid patient rehabilitation of facial defects. 

PMID- 23956598
TI  - Mucormycosis in maxilla: Rehabilitation of facial defects using interim removable
      prostheses: A clinical case report.
AB  - Maxilla is one of the facial bones with rich vascular supply. Necrosis of
      maxillary bone is rare and may occur due to infection, trauma and rare metabolic
      disorders. Maxilla is essential bone forming the roof of oral cavity.
      Mucormycosis is one of the most common fungal infection, which affects maxilla
      especially in diabetes and immunocompromised patients. We report a case of
      maxillary necrosis due to mucormycosis in an uncontrolled diabetic patient. Early
      diagnosis and prompt treatment can reduce the mortality and morbidity of this
      lethal fungal infection. 

PMID- 23956599
TI  - Benign fibroushistiocytoma of the gingiva.
AB  - Benign fibroushistiocytoma is a benign connective tissue tumor rarely seen
      affecting the head and neck region. These tumors were believed to be of
      histiocytic origin as they are comprised of cells, which showed spindled
      morphology and cells with a round histiocytic appearance. The current concept
      consents that the lesional cells rather represent a fibroblastic differentiation.
      Diagnosis of these tumors proves to be challenging even with the use of
      immunohistochemistry due to lack of any specific markers. Here, we describe a
      case which presented in the gingiva mimicking a reactive lesion, which in fact
      was a tumor. 

PMID- 23956600
TI  - Early correction of class III malocclusion with rapid maxillary expansion and
      face mask therapy.
AB  - A case report is presented of a class III malocclusion with a class III skeletal
      pattern and maxillary retrusion. Patient, a 10-year-old boy was treated with an
      orthopedic face mask in conjunction with rapid maxillary expansion and standard
      pre-adjusted edgewise appliance. Treatment was completed after 3 years and proved
      to be stable following the active treatment. 

PMID- 23956601
TI  - Treatment of class 2 division 1 malocclusion with severe short roots of upper
      central incisors.
AB  - The average amount of resorption per root of examined maxillary incisors or
      anterior teeth is < 1.5 mm during comprehensive orthodontic treatment. About 5%
      of adults and 2% of adolescents are likely to have at least one tooth with
      resorption of more than 5 mm during active treatment. Although resorption stops
      once the active appliances are removed, fortunately, truly severe resorption that
      threatens the longevity of the tooth or forces a halt to treatment is rare. The
      fact is, however that orthodontic tooth movement does directly cause irreversible
      resorption of the root. As the movers of the teeth, it is incumbent for us to
      know as much as possible about the causes, effects and prevention of this
      phenomenon. 

PMID- 23956603
TI  - Palatal pyogenic granulomaa.
AB  - Pyogenic granuloma (PG) is a kind of inflammatory hyperplasia seen in the oral
      cavity. This term is a misnomer because the lesion is unrelated to infection. In
      reality it arises in response to various stimuli such as low-grade local
      irritation, traumatic injury or hormonal factors. It predominantly occurs in the
      second decade of life in young females possibly because of the vascular effects
      of female hormones. It is also called as pregnancy tumor because of its high
      frequency of occurrence during the early part of pregnancy. Even though, this
      lesion is non-neoplastic and treatment procedure is simple, it should be
      diagnosed correctly before proceeding with the treatment. The most common site
      for PGs is gingiva (75%) and rarely in the palate. In this case report, we are
      going to present very rare occurrence of pregnancy tumor in the hard palate. 

PMID- 23956602
TI  - Nasal prosthesis for a patient with xeroderma pigmentosum.
AB  - Acquired facial defects caused by extirpation of neoplasms, congenital
      malformations or traumatic injury results in a huge functional, cosmetic and
      psychological handicap in those patients. These defects can be restored by facial
      prosthesis using different materials and retention methods to achieve a lifelike
      appearance and function. This clinical report describes a treatment schedule
      using silicone nasal prosthesis, which is mechanically retained for a patient who
      has undergone a partial rhinectomy due to basal cell carcinoma of the nose. The
      prosthesis was made to restore the esthetic appearance of patient with a
      mechanically retained design using a spectacle glass frame without any prosthetic
      adhesives so that the patient is more comfortable and confident to resume daily
      activities. 

PMID- 23956604
TI  - Hypodontia and hypoplasia of mandible: A rare defect caused by combination
      therapy.
AB  - Hypodontia is defined as the developmental absence of one or more tooth and it
      can present in varying degrees of severity and severe hypodontia has been defined
      as the absence of six teeth, excluding third molars. Radiation plays an important
      role in the treatment of head and neck cancer, in spite of its benefits,
      radiation has several side-effects in the head and neck region. This article
      highlights a case report, where hypodontia, hypoplasia of mandible, stunded
      permanent teeth roots, microdontia, inversion of tooth bud were observed in 19
      years old patient who was diagnosed with Langerhans cell histiocytosis at her age
      of 3 years she had received a combination of radiotherapy and chemotherapy for a
      period of 1 year and radiation of 50 Gy was used in the head and neck region.
      Radiographs were taken and it revealed abnormal changes in growth and development
      of bone and teeth. 

PMID- 23956605
TI  - Non-extraction treatment of severe crowding with pendulum appliance.
AB  - An extraction case was planned for non-extraction treatment using pendulum
      appliance and the effect of appliance was evaluated in a 14-year-old girl with a
      severe maxillary and mandibular crowding followed by non-extraction fixed
      appliance preadjusted edgewise appliance mechanotherapy. Total treatment time was
      for 22 months. The obtuse nasolabial angle was maintained intact. Correction of
      crowding, co-ordinated arch forms was achieved with molar distalization. The
      impetus on soft-tissue paradigm is stressed in this case report and pendulum
      appliance can indeed boost our clinical acumen and swing our priorities toward
      non-extraction treatment. 

PMID- 23956606
TI  - Interdisciplinary approach for bilateral maxillary canine: First premolar
      transposition with complex problems in an adult patient.
AB  - Adult patients seeking orthodontic care were increased nowadays not only on
      esthetic need but also on functional demand. But problems with adult patients
      were not only malocclusions but also dental caries, pulpal pathology, missing
      teeth, muco-gingival problems and loss of supporting structures. We report here a
      case of 35-year-old female with complete transposition referred as a positional
      interchange of two permanent teeth within the same quadrant of the dental arch
      along with gingival recession of the lower anteriors and missing molars. Gingival
      health was improved by free gingival graft in lower anteriors followed by fixed
      orthodontic procedure to correct transposition. Based on transposition crown
      recontouring and restoration was done along with replacement of missing molars
      with fixed prosthesis. Thus, proper treatment planning with interdisciplinary
      management improves not only the esthetics and occlusal relationship but also
      with stable results. 

PMID- 23956607
TI  - Oral myiasis in a maxillofacial trauma patient.
AB  - Myiasis is a rare disease primarily caused by the invasion of tissue by larvae of
      certain dipteran flies. Oral myiasis is still more "rare" and "unique" owing to
      the fact that oral cavity rarely provides the necessary habitat conducive for a
      larval lifecycle. Common predisposing factors are poor oral hygiene, halitosis,
      trauma, senility, learning disabilities, physically and mentally challenged
      conditions. Oral myiasis can lead to rapid tissue destruction and disfigurement
      and requires immediate treatment. Treatment consists of manual removal of maggots
      from the oral cavity after application of chemical agents. Good sanitation,
      personal and environmental hygiene and cleanliness and special care for
      debilitated persons are the best methods to prevent oral myiasis. This case
      report describes the presentation of oral myiasis caused by musca nebulo (common
      house fly) in a 40-year-old male patient, with recent maxillofacial trauma. The
      patient was treated by manual removal larvae by topical application of turpentine
      oil, followed by surgical debridement of the wound and open reduction and
      internal fixation of the fracture. 

PMID- 23956608
TI  - Reconstruction of maxillary cemento-ossifying fibroma defect with buccal pad of
      fat.
AB  - A cemento-ossifying fibroma (COF) is a rare benign neoplasm of maxilla when
      compared with mandible (World Health Organization, 1992). COF of maxilla may be
      quite large and locally very aggressive lesion. These tumor mass was peeled out
      by en-bloc excision using gentle blunt dissection. This paper presents 35-year
      old male patient who had a gradually expanding lobular mass in the left maxillary
      posterior region for past 1 year. He has been treated successfully by surgical en
      bloc resection. Various techniques were used to reconstruction the defect. Buccal
      pad of fat is a simple technique having advantages like good vascularity,
      adaptability, good closure of the defect with favorable prognosis. 

PMID- 23956609
TI  - A laboratory silicone for preclinical training in ear prosthesis.
AB  - This article describes an industrial elastic silicone as a material for the
      laboratory fabrication of ear prosthesis. It has been tested for toxicity in lab
      animals by the SGS India Pvt. Ltd and approved as a material to pass the
      parameter of abnormal toxicity. This material therefore can be safely recommended
      for laboratory exercise to fabricate facial prosthesis. The high cost of the
      maxillo facial silicone materials prohibits their use for facial prosthesis in
      pre-clinical training of post-graduate students in maxillofacial prosthodontics.
      For this reason, pre-clinical laboratory exercise in facial prosthesis is
      inadequate. A few institutions use polymethyl methacrylate resins which are rigid
      and do not have elastic characteristics of silicone, which is used for facial
      defects. This cost-effective industrial silicone material which mimics the
      elastic and color characteristics of the conventional silicones can be
      recommended for preclinical exercises. 

PMID- 23956610
TI  - ON MODEL SELECTION STRATEGIES TO IDENTIFY GENES UNDERLYING BINARY TRAITS USING
      GENOME-WIDE ASSOCIATION DATA.
AB  - For more fruitful discoveries of genetic variants associated with diseases in
      genome-wide association studies, it is important to know whether joint analysis
      of multiple markers is more powerful than the commonly used single-marker
      analysis, especially in the presence of gene-gene interactions. This article
      provides a statistical framework to rigorously address this question through
      analytical power calculations for common model search strategies to detect binary
      trait loci: marginal search, exhaustive search, forward search, and two-stage
      screening search. Our approach incorporates linkage disequilibrium, random
      genotypes, and correlations among score test statistics of logistic regressions.
      We derive analytical results under two power definitions: the power of finding
      all the associated markers and the power of finding at least one associated
      marker. We also consider two types of error controls: the discovery number
      control and the Bonferroni type I error rate control. After demonstrating the
      accuracy of our analytical results by simulations, we apply them to consider a
      broad genetic model space to investigate the relative performances of different
      model search strategies. Our analytical study provides rapid computation as well
      as insights into the statistical mechanism of capturing genetic signals under
      different genetic models including gene-gene interactions. Even though we focus
      on genetic association analysis, our results on the power of model selection
      procedures are clearly very general and applicable to other studies.

PMID- 23956611
TI  - VARIABLE SELECTION IN PARTLY LINEAR REGRESSION MODEL WITH DIVERGING DIMENSIONS
      FOR RIGHT CENSORED DATA.
AB  - Recent biomedical studies often measure two distinct sets of risk factors: low
      dimensional clinical and environmental measurements, and high-dimensional gene
      expression measurements. For prognosis studies with right censored response
      variables, we propose a semiparametric regression model whose covariate effects
      have two parts: a nonparametric part for low-dimensional covariates, and a
      parametric part for high-dimensional covariates. A penalized variable selection
      approach is developed. The selection of parametric covariate effects is achieved
      using an iterated Lasso approach, for which we prove the selection consistency
      property. The nonparametric component is estimated using a sieve approach. An
      empirical model selection tool for the nonparametric component is derived based
      on the Kullback-Leibler geometry. Numerical studies show that the proposed
      approach has satisfactory performance. Application to a lymphoma study
      illustrates the proposed method.

PMID- 23956612
TI  - Multicenter study of human papillomavirus and the human papillomavirus vaccine:
      knowledge and attitudes among people of African descent.
AB  - OBJECTIVE: To compare knowledge and attitudes of human papillomavirus (HPV) and
      the vaccine between different cultures of African descent. METHODS: A cross
      sectional survey of 555 African-Americans and Afro-Caribbeans residing in the US
      and the Bahamas (BHM) was conducted. RESULTS: General knowledge about HPV and the
      HPV vaccine differed between the two countries significantly. Bahamian
      respondents were less likely to have higher numbers of correct knowledge answers
      when compared to Americans (Adjusted Odds Ratio [Adj. OR] 0.47, 95% Confidence
      Interval [CI] 0.30-0.75). Older age, regardless of location, was also associated
      with answering fewer questions correctly (Adj. OR 0.61, 95% CI 0.40-0.92).
      Attitudes related to HPV vaccination were similar between the US and BHM, but
      nearly 80% of BHM respondents felt that children should not be able to receive
      the vaccine without parental consent compared to 57% of American respondents.
      CONCLUSIONS: Grave lack of knowledge, safety and cost concerns, and influence of
      parental restrictions may negatively impact vaccine uptake among African-American
      and Afro-Caribbean persons. Interventions to increase the vaccine uptake in the
      Caribbean must include medical provider and parental involvement. Effective
      strategies for education and increasing vaccine uptake in BHM are crucial for
      decreasing cervical cancer burden in the Caribbean.

PMID- 23956613
TI  - Effectiveness and safety of endoscopic treatment of benign biliary strictures
      using a new fully covered self expandable metal stent.
AB  - Background. In patients with benign biliary strictures, the use of fully covered
      self-expandable metal stents (SEMS) has been proposed as an alternative to
      plastic stenting, but high quality prospective data are sparse. This study was
      performed to evaluate the long-term effectiveness and safety of a new fully
      covered SEMS for benign biliary strictures. Methods. All consecutive patients
      with benign biliary strictures were treated with placement of a fully covered
      SEMS (WallFlex) for 6 months. Short- and long-term stricture resolution, adverse
      events, and ease of stent removal were recorded. Results. 23 patients were
      enrolled. Stricture etiology was chronic pancreatitis (14), postorthotopic liver
      transplant (4), idiopathic (4), and biliary stones (1). All ERCPs were
      technically successful. All stents were successfully removed. Short-term
      stricture resolution was seen in 22/23 (96%) patients. Long-term success was
      15/18 (83.3%). All 3 failures were patients with biliary strictures in the
      setting of chronic calcific pancreatitis. Conclusions. The use of the new SEMS
      for the treatment of benign biliary strictures led to short-term stricture
      resolution in the vast majority of patients. Over a long-term followup the
      success rate appears favorable compared to historical results achieved with
      multiple plastic stenting, particularly in patients with chronic pancreatitis.
      The study was registered with ClinicalTrials.gov (NCT01238900). 

PMID- 23956614
TI  - Synthesis and evaluation of cationic bacteriochlorin amphiphiles with effective
      in vitro photodynamic activity against cancer cells at low nanomolar
      concentration.
AB  - Bacteriochlorins are attractive candidates as photosensitizers for photodynamic
      therapy (PDT) due to their intense absorption in the near-infrared (NIR) region
      of the spectrum where light transmission through tissue is maximal. Many
      naturally occurring bacteriochlorins are inherently unstable due to adventitious
      atmospheric oxidation. A de novo synthesis affords bacteriochlorins that contain
      a geminal dimethyl group in each reduced pyrrole ring to increase stability
      against oxidation. Here, three new synthetic bacteriochlorins, each bearing a
      single side-chain containing one or two positive charges, were investigated for
      their in vitro PDT activity against HeLa human cancer cells. All bacteriochlorins
      were active at low nanomolar concentration when activated with NIR light; those
      bearing a single positive charge exhibited faster uptake and higher activity. The
      bacteriochlorins were localized in mitochondria, lysosomes and endoplasmic
      reticulum as shown by organelle specific fluorescent probes. Cell death was via
      apoptosis as shown by cell morphology and nuclear condensation. Taken together,
      the results show the importance of appropriate peripheral groups about a
      photosensitizer for effective PDT applications.

PMID- 23956615
TI  - A Regression Framework for Effect Size Assessments in Longitudinal Modeling of
      Group Differences.
AB  - The use of growth modeling analysis (GMA)--particularly multilevel analysis and
      latent growth modeling--to test the significance of intervention effects has
      increased exponentially in prevention science, clinical psychology, and
      psychiatry over the past 15 years. Model-based effect sizes for differences in
      means between two independent groups in GMA can be expressed in the same metric
      (Cohen's d) commonly used in classical analysis and meta-analysis. This article
      first reviews conceptual issues regarding calculation of d for findings from GMA
      and then introduces an integrative framework for effect size assessments that
      subsumes GMA. The new approach uses the structure of the linear regression model,
      from which effect sizes for findings from diverse cross-sectional and
      longitudinal analyses can be calculated with familiar statistics, such as the
      regression coefficient, the standard deviation of the dependent measure, and
      study duration.

PMID- 23956616
TI  - Group-based social skills interventions for adolescents with higher-functioning
      autism spectrum disorder: a review and looking to the future.
AB  - In this paper, we synthesize the current literature on group-based social skills
      interventions (GSSIs) for adolescents (ages 10-20 years) with higher-functioning
      autism spectrum disorder and identify key concepts that should be addressed in
      future research on GSSIs. We consider the research participants, the
      intervention, the assessment of the intervention, and the research methodology
      and results to be integral and interconnected components of the GSSI literature,
      and we review each of these components respectively. Participant characteristics
      (eg, age, IQ, sex) and intervention characteristics (eg, targeted social skills,
      teaching strategies, duration and intensity) vary considerably across GSSIs;
      future research should evaluate whether participant and intervention
      characteristics mediate/moderate intervention efficacy. Multiple assessments (eg,
      parent-report, child-report, social cognitive assessments) are used to evaluate
      the efficacy of GSSIs; future research should be aware of the limitations of
      current measurement approaches and employ more accurate, sensitive, and
      comprehensive measurement approaches. Results of GSSIs are largely inconclusive,
      with few consistent findings across studies (eg, high parent and child
      satisfaction with the intervention); future research should employ more rigorous
      methodological standards for evaluating efficacy. A better understanding of these
      components in the current GSSI literature and a more sophisticated and rigorous
      analysis of these components in future research will lend clarity to key
      questions regarding the efficacy of GSSIs for individuals with autism spectrum
      disorder.

PMID- 23956617
TI  - Isolation and identification of Aspergillus section fumigati strains from arable
      soil in Korea.
AB  - 63 strains of Aspergillus section Fumigati were isolated from 17 samples of
      arable soil in a central province of Korea. Based on the results of genotypic and
      phenotypic analyses, they were identified as Aspergillus fumigatus, A. lentulus,
      Neosartorya coreana, N. fennelliae, N. fischeri, N. glabra, N. hiratsukae, N.
      laciniosa, N. pseudofischeri, N. quadricincta, N. spinosa and N. udagawae. Among
      these, N. fennelliae, N. hiratsukae, N. quadricincta, and N. udagawae had not
      been previously recorded in Korea. The diversity of Aspergillus section Fumigati
      species from arable soil in Korea is also addressed. 

PMID- 23956618
TI  - Identification and Characterization of Gliocladium viride Isolated from Mushroom
      Fly Infested Oak Log Beds Used for Shiitake Cultivation.
AB  - A green mold species that has not previously been reported in Korea was isolated
      from oak log beds used for shiitake (Lentinula edodes) cultivation that were
      infested by mushroom flies. In this study, we identify the mold species as
      Gliocladium viride (an anamorph of Hypocrea lutea) and describe its mycological
      properties. The fungus was cottony on both potato dextrose agar (PDA) and Czapek
      yeast extract agar (CYA), but was colored white on PDA and became yellowish green
      and brown on CYA. Mycelial growth on PDA attained a diameter of 73 mm at 30C
      after 5 days. The fungus grew faster on malt extract agar (> 80 mm, 5 days at
      25C) compared to CYA and PDA (< 68 mm, 5 days at 25C). Penicillate conidiophores
      of the fungus are hyaline, smooth walled, branching above typically in four
      stages, and 120~240 um in length. Club-shaped or slender phialides are formed on
      the metulae. Conidia of the fungus were ovate and elliptic, yellowish brown and
      green, and 2.5~3.0 um * 1.8~2.3 um in size. Typically, slimy conidia are formed
      in a mass and colored brown to dark green to almost black. The internal
      transcribed spacer rDNA and translation elongation factor 1 alpha gene sequences
      of the fungus isolated here show 99% identity with previously identified G.
      viride strains. 

PMID- 23956619
TI  - Successful Development of Cordyceps bassiana Stromata from Beauveria bassiana.
AB  - A specimen of Beauveria bassiana was collected from Yang-yang of Gangwon
      province, Korea in October 2006. Conidial isolates were prepared from the
      specimen by the dilution method and inoculated in brown rice medium for fruiting
      body production. After nearly two months incubation for perithecial stromata
      developed from single isolates as well as from their combinations. They were
      determined as Cordyceps bassiana by observing the stromatal characters and their
      conidial structures. This is the first report of the development of C. bassiana
      from B. bassiana cultures. 

PMID- 23956620
TI  - Cultural Conditions for Mycelial Growth and Molecular Phylogenetic Relationship
      in Different Wild Strains of Schizophyllum commune.
AB  - The common split-gilled mushroom, Schizophyllum commune is found throughout the
      world on woody plants. This study was initiated to evaluate conditions for
      favorable vegetative growth and to determine molecular phylogenetic relationship
      in twelve different strains of S. commune. A suitable temperature for mycelial
      growth was obtained at 30C. This mushroom grew well in acidic conditions and pH 5
      was the most favorable. Hamada, glucose peptone, Hennerberg, potato dextrose agar
      and yeast malt extract were favorable media for growing mycelia, while Lilly and
      glucose tryptone were unfavorable. Dextrin was the best and lactose was the less
      effective carbon source. The most suitable nitrogen sources were calcium nitrate,
      glycine, and potassium nitrate, whereas ammonium phosphate and histidine were the
      least effective for the mycelial growth of S. commune. The genetic diversity of
      each strain was investigated in order to identify them. The internal transcribed
      spacer (ITS) regions of rDNA were amplified using PCR. The size of the ITS1 and
      ITS2 regions of rDNA from the different strains varied from 129 to 143 bp and 241
      to 243 bp, respectively. The sequence of ITS1 was more variable than that of
      ITS2, while the 5.8S sequences were identical. A phylogenetic tree of the ITS
      region sequences indicated that the selected strains were classified into three
      clusters. The reciprocal homologies of the ITS region sequences ranged from 99 to
      100%. The strains were also analyzed by random amplification of polymorphic DNA
      (RAPD) with 20 arbitrary primers. Twelve primers efficiently amplified the
      genomic DNA. The number of amplified bands varied depending on the primers used
      or the strains tested. The average number of polymorphic bands observed per
      primer was 4.5. The size of polymorphic fragments was obtained in the range of
      0.2 to 2.3 kb. These results indicate that the RAPD technique is well suited for
      detecting the genetic diversity in the S. commune strains tested. 

PMID- 23956621
TI  - Functional Characterization of cAMP-Regulated Gene, CAR1, in Cryptococcus
      neoformans.
AB  - The cyclic AMP (cAMP) pathway plays a major role in growth, sexual
      differentiation, and virulence factor synthesis of pathogenic fungi. In
      Cryptococcus neoformans, perturbation of the cAMP pathway, such as a deletion in
      the gene encoding adenylyl cyclase (CAC1), causes defects in the production of
      virulence factors, including capsule and melanin production, as well as mating.
      Previously, we performed a comparative transcriptome analysis of the Ras- and
      cAMP-pathway mutants, which revealed 163 potential cAMP-regulated genes (38 genes
      at a 2-fold cutoff). The present study characterized the role of one of the cAMP
      pathway-dependent genes (serotype A identification number CNAG_ 06576.2). The
      expression patterns were confirmed by Northern blot analysis and the gene was
      designated cAMP-regulated gene 1 (CAR1). Interestingly, deletion of CAR1 did not
      affect biosynthesis of any virulence factors and the mating process, unlike the
      cAMP-signaling deficient cac1Delta mutant. Furthermore, the cac1Delta mutant
      exhibited wild-type levels of the stress-response phenotype against diverse
      environmental cues, indicating that Car1, albeit regulated by the cAMP-pathway,
      is not essential to confer a cAMP-dependent phenotype in C. neoformans. 

PMID- 23956622
TI  - Direct Detection of Cylindrocarpon destructans, Root Rot Pathogen of Ginseng by
      Nested PCR from Soil Samples.
AB  - We have successfully applied the nested PCR to detect Cylindrocarpon destructans,
      a major pathogen causing root rot disease from ginseng seedlings in our former
      study. The PCR assay, in this study, was used to detect the pathogen from soils.
      The nested PCR using internal transcribed spacer (ITS) 1, 4 primer set and Dest
      1, 4 primer set maintained the specificity in soils containing various
      microorganisms. For a soil DNA extraction method targeting chlamydospores, when
      several cell wall disrupting methods were tested, the combination of
      lyophilization and grinding with glass beads, which broke almost all the
      chlamydospores, was the strongest. The DNA extraction method which was completed
      based on the above was simple and time-saving because of exclusion of unnecessary
      stages, and efficient to apply in soils. As three ginseng fields whose histories
      were known were analyzed, the PCR assay resulted as our expectation derived from
      the field information. The direct PCR method will be utilized as a reliable and
      rapid tool for detecting and monitoring C. destructans in ginseng fields. 

PMID- 23956623
TI  - The Effect of Nano-Silver Liquid against the White Rot of the Green Onion Caused
      by Sclerotium cepivorum.
AB  - White rot, which is caused by Sclerotium cepivorum, is a lethal disease affecting
      green onions. Three different types of nano-silver liquid (WA-CV-WA13B, WA-AT
      WB13R, and WA-PR-WB13R) were tested in several different concentrations on three
      types of media to assess their antifungal activities. Results from in vitro
      experiments showed that all three of the nano-silver liquids had more than 90%
      inhibition rates at a concentration of 7 ppm. Greenhouse experiments revealed
      that all of the nano-silver liquids increased biomass and dry weights, and there
      were minimal changes in the population of various bacteria and fungi from the
      soil of greenhouse-cultivated green onions. In addition, a soil chemical analysis
      showed that there were minimal changes in soil composition. 

PMID- 23956624
TI  - The Anti-inflammatory Effects of Water Extract from Cordyceps militaris in Murine
      Macrophage.
AB  - The aim of this study was to determine the in vitro anti-inflammatory effect of
      hot water extract from Cordyceps militaris fruiting bodies (CMWE) on
      lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production, tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-6 (IL-6) release in RAW 264.7 cells. The
      treatment of macrophages with various concentrations of hot CMWE significantly
      reduced LPS-induced production as well as NO, TNF-alpha and IL-6 secretion in a
      concentration-dependent manner. These results suggest that CMWE have potent
      inhibitory effects on the production of these inflammatory mediators. 

PMID- 23956625
TI  - Extraction and Characteristics of Anti-obesity Lipase Inhibitor from Phellinus
      linteus.
AB  - To develop a potent anti-obesity lipase inhibitor from mushroom, the lipase
      inhibitory activities of various mushroom extracts were determined. Methanol
      extracts from Phellinus linteus fruiting body exhibited the highest lipase
      inhibitory activity (72.8%). The inhibitor was maximally extracted by treatment
      of a P. linteus fruiting body with 80% methanol at 40C for 24 hr. After partial
      purification by systematic solvent extraction, the inhibitor was stable in the
      range of 40~80C and pH 2.0~9.0. In addition to lipase inhibitory activity, the
      inhibitor showed 59.4% of superoxide dismutase-like activity and 56.3% of
      acetylcholinesterase inhibitory activity. 

PMID- 23956626
TI  - Optimal Extraction Conditions of Anti-obesity Lipase Inhibitor from Phellinus
      linteus and Nutritional Characteristics of the Extracts.
AB  - In an effort to develop novel mushroom-derived anti-obesity nutraceuticals, water
      and ethanol extracts containing the lipaseinhibitory compound from Phellinus
      linteus were prepared, and their nutritional components were determined. The
      optimal conditions for the extraction of P. linteus lipase inhibitor involved the
      treatment of the fruiting bodies with distilled water at 80C for 72 hr and 80%
      ethanol at 100C for 60 hr, respectively. The distilled water extract and ethanol
      extract contained 10.9% and 6.11% of crude protein, and 0.96% and 15.86% of crude
      fat, respectively. Additionally, the distilled water extract contained a large
      quantity of minerals, including 239.5 mg of K, 39.3 mg of Mg, and 39.3 mg of Na.
      The free amino acid content of the distilled water extracts was also higher than
      that of the ethanol extracts, and in particular, the distilled water extracts
      contained 5,139 mg of asparagine, 3,891 mg of tryptophan, 2,598 mg of alanine,
      and 2,066 mg of serine in 100 g of the distilled water extracts. 100 g of the
      distilled water and ethanol extracts were found to contain 12.31 g and 8.16 g of
      malic acid, respectively. 

PMID- 23956627
TI  - Identification of Sculptolumina japonica (Physciaceae) in South Korea.
AB  - The paper describes identification of new microlichen (Sculptolumina japonica) in
      South Korea. A detailed taxonomic description and comments are presented for the
      taxa studied. Lichen genus Sculptolumina is reported for the first time for this
      country. 

PMID- 23956628
TI  - Notes on Lichen Genus Buellia De Not. (lichenized Ascomycetes) from South Korea.
AB  - Based on a literature survey and assessment of the important features of lichen
      genus Buellia (spore shape and size, anatomy of the exciple as well as analysis
      of the lichen substances), the present paper describes four new records of B.
      maritima, B. polyspora, B. spuria and B. stellulata from South Korea. Among them,
      B. maritima and B. polyspora are firstly reported in East Asia including in
      China, the Korean Peninsula and Japan. Brief description of all the new records
      along with earlier described species placed under genus Amandinea and Hafellia
      are provided with their distribution and chemistry. A key to all the Buellia
      species reported so far from South Korea is also provided. 

PMID- 23956629
TI  - Screening of Cell Cycle-Related Genes of Pleurotus eryngii Using Yeast Mutant
      Strains.
AB  - Temperature-sensitive yeast mutants were used to screen for cell cycle-related
      genes from Pleurotus eryngii genomic DNA. A mushroom genomic DNA library was
      established and each gene was screened for the ability to rescue seven
      Saccharomyces cerevisiae temperature-sensitive strains. Hundreds of yeast
      transformants were selected at restrictive temperatures over 30C. Plasmids from
      the transformants that survived were isolated and transformed back into their
      host strains. The temperature sensitivity of the resulting transformants was
      tested from 30C to 37C. Ten DNA fragments from P. eryngii were able to rescue
      yeast temperature-sensitive strains, and their DNA sequences were determined. 

PMID- 23956630
TI  - Development of Detection Methods for Cellulolytic Activity of Auricularia
      auricula-judae.
AB  - To obtain basic information on the detection of cellulolytic activity in
      Auricularia auricula-judae, the influences of dye reagent, pH, and temperature
      were assessed. Chromogenic dye (congo red, phenol red, remazol brilliant blue,
      and trypan blue) was individually incorporated into a medium containing either
      carboxymethyl-cellulose, Avicel, or D-cellobiose as a polysaccharide carbon
      substrate. The other assessments utilized pHs ranging from 4.5 to 8.0 and
      temperatures from 15~35C. Overall, when A. auricula-judae species were
      transferred onto media contained Congo red and adjusted pH 7.0 and then incubated
      at 25C for 5 days, the clear zone indicative of cellulolytic activity was more
      pronounced. 

PMID- 23956631
TI  - Leaf Spot of Yam Caused by Pseudophloeosporella dioscoreae in Korea.
AB  - Leaf spot symptoms were frequently observed on yam plants grown in the Yeoju area
      in Korea during a disease survey in 2008. A total of five isolates of
      Pseudophloeosporella sp. were obtained from the infected leaves of yam plants.
      All of the isolates were identified as Pseudophloeosporella dioscoreae based on
      their morphological and cultural characteristics. A phylogenetic tree derived
      from the internal transcribed spacer sequences of the fungal isolates showed that
      the fungus is distinctly separated from species in other related genera. P.
      dioscoreae isolates caused very tiny spots on leaves of yam plants two weeks
      after artificial inoculation which were similar to those observed in the field.
      This is the first report that Pseudophloeosporella dioscoreae causes leaf spot in
      yams in Korea. 

PMID- 23956632
TI  - Eight unrecorded higher fungi identified at the Korea national arboretum.
AB  - A total of 560 higher fungal specimens were collected in the Gwangneung Forest
      from May to November of 2007. All of the collected specimens were identified;
      categorized into 8 classes, 19 orders, 69 families, 165 genera, and 296 species;
      and deposited in the herbarium of the Korea National Arboretum. Of the identified
      specimens, 8 were confirmed as being new to Korea and are as follows: Cudoniella
      acicularis (Korean name: Jeombakisotugubeoseos), Discina ancilis (Korean name:
      Jomwonbanbeoseos), Helvella costifera (Korean name: Galbidaeanjangbeoseos),
      Entoloma cephalotrichum (Korean name: Jomkkaltaejiweodaebeoseos), Mycena
      leptocephala (Korean name: Yalbeungatweojuleumbeoseos), Naematoloma gracile
      (Korean name: Ganeundaegaeambeoseos), Sistotrema octosporum (Korean name:
      Hweosekcheonbeoseos), and Hydnellum peckii (Korean name: Pijeopkkaltaegibeoseos).

PMID- 23956633
TI  - Mycelial Propagation and Molecular Phylogenetic Relationships of Commercially
      Cultivated Agrocybe cylindracea based on ITS Sequences and RAPD.
AB  - This study evaluated the optimal vegetative growth conditions and molecular
      phylogenetic relationships of eleven strains of Agrocybe cylindracea collected
      from different ecological regions of Korea, China and Taiwan. The optimal
      temperature and pH for mycelial growth were observed at 25C and 6. Potato
      dextrose agar and Hennerberg were the favorable media for vegetative growth,
      whereas glucose tryptone was unfavorable. Dextrin, maltose, and fructose were the
      most effective carbon sources. The most suitable nitrogen sources were arginine
      and glycine, whereas methionine, alanine, histidine, and urea were least
      effective for the mycelial propagation of A. cylindracea. The internal
      transcribed spacer (ITS) regions of rDNA were amplified using PCR. The sequence
      of ITS2 was more variable than that of ITS1, while the 5.8S sequences were
      identical. The reciprocal homologies of the ITS sequences ranged from 98 to 100%.
      The strains were also analyzed by random amplification of polymorphic DNA (RAPD)
      using 20 arbitrary primers. Fifteen primers efficiently amplified the genomic
      DNA. The average number of polymorphic bands observed per primer was 3.8. The
      numbers of amplified bands varied based on the primers and strains, with
      polymorphic fragments ranging from 0.1 to 2.9 kb. The results of RAPD analysis
      were similar to the ITS region sequences. The results revealed that RAPD and ITS
      techniques were well suited for detecting the genetic diversity of all A.
      cylindracea strains tested. 

PMID- 23956634
TI  - Effect of Different Substrates and Casing Materials on the Growth and Yield of
      Calocybe indica.
AB  - Calocybe indica, a tropical edible mushroom, is popular because it has good
      nutritive value and it can be cultivated commercially. The current investigation
      was undertaken to determine a suitable substrate and the appropriate thickness of
      casing materials for the cultivation of C. indica. Optimum mycelial growth was
      observed in coconut coir substrate. Primordia initiation with the different
      substrates and casing materials was observed between the 13th and 19th day. The
      maximum length of stalk was recorded from sugarcane leaf, while diameter of stalk
      and pileus, and thickness of pileus were found in rice straw substrate. The
      highest biological and economic yield, and biological efficiency were also
      obtained in the rice straw substrate. Cow dung and loamy soil, farm-yard manure,
      loamy soil and sand, and spent oyster mushroom substrates were used as casing
      materials to evaluate the yield and yield-contributing characteristics of C.
      indica. The results indicate that the number of effective fruiting bodies, the
      biological and economic yield, and the biological efficiency were statistically
      similar all of the casing materials used. The maximum biological efficiency was
      found in the cow dung and loamy soil casing material. The cow dung and loamy soil
      (3 cm thick) was the best casing material and the rice straw was the best
      substrate for the commercial cultivation of C. indica. 

PMID- 23956635
TI  - Deletion of GBG1/AYR1 Alters Cell Wall Biogenesis in Saccharomyces cerevisiae.
AB  - We identified a gene for beta-1,3-glucan synthesis (GBG1), a nonessential gene
      whose disruption alters cell wall synthesis enzyme activities and cell wall
      composition. This gene was cloned by functional complementation of defects in
      beta-1,3-glucan synthase activity of the the previously isolated Saccharomyces
      cerevisiae mutant LP0353, which displays a number of cell wall defects at
      restrictive temperature. Disruption of the GBG1 gene did not affect cell
      viability or growth rate, but did cause alterations in cell wall synthesis enzyme
      activities: reduction of beta-1,3-glucan synthase and chitin synthase III
      activities as well as increased chitin synthase I and II activities. GBG1
      disruption also showed altered cell wall composition as well as susceptibility
      toward cell wall inhibitors such as Zymolyase, Calcofluor white, and Nikkomycin
      Z. These results indicate that GBG1 plays a role in cell wall biogenesis in S.
      cerevisiae. 

PMID- 23956636
TI  - Possible Roles of LAMMER Kinase Lkh1 in Fission Yeast by Comparative Proteome
      Analysis.
AB  - To investigate the possible roles of LAMMER kinase homologue, Lkh1, in
      Schizosaccharomyces pombe, whole proteins were extracted from wild type and lkh1
      deletion mutant cells and subjected to polyacrylamide gel electrophoresis.
      Differentially expressed proteins were identified by tandem mass spectrometry
      (MS/MS) and were compared with a protein database. In whole-cell extracts, 10
      proteins were up-regulated and 9 proteins were down-regulated in the mutant. In
      extracellular preparations, 6 proteins were up-regulated in the lkh1 (+) null
      mutant and 4 proteins successfully identified: glycolipid anchored surface
      precursor, beta-glucosidase (Psu1), cell surface protein, glucan 1,3-beta
      glucosidase (Bgl2), and exo-1,3 beta-glucanase (Exg1). These results suggest that
      Lkh1 is involved in regulating cell wall assembly. 

PMID- 23956637
TI  - Biological Control of Alternaria Fruit Rot of Chili by Trichoderma Species under
      Field Conditions.
AB  - Trichoderma strains were evaluated under field conditions to assay their efficacy
      in suppressing Alternaria fruit rot disease and promoting chili plant growth. The
      experiment was conducted at the Botanical Garden, Rajshahi University, Bangladesh
      from July 2006 to March 2007. Application of Trichoderma harzianum IMI 392432
      significantly (p = 0.05) suppressed the disease compared to Alternaria tenuis
      (T2) treatment and improved both growth and yield. The treatment T4 (T. harzianum
      IMI-392432 + A. tenuis) was most effective in reducing disease percentage
      (72.27%) compared to A. tenuis (T1) treatment. The highest seed germination rate
      (85.56%) and the highest growth and yield (12.5 g/plant) was also recorded in the
      same treatment (T4), followed by T5 (T. harzianum IMI-392433 000000 + A. tenuis),
      T6 (T. harzianum IMI-392434 +A. tenuis), T2 (T. virens IMI-392430 + A. tenuis),
      and T3 (T. pseudokoningii IMI-392431 +A. tenuis) treatment, while single
      treatment with A. tenuis significantly decreased these values. 

PMID- 23956638
TI  - Cultural Characteristics and Fruiting Body Production in Cordyceps bassiana.
AB  - Single ascospore isolates of Cordyceps bassiana were observed for their colony
      pigmentation on Sabouraud Dextrose agar plus Yeast Extract (SDAY) plates and were
      inoculated in a brown rice medium for production of fruiting bodies. Colony
      pigmentation did not show any relationship with perithecial stromata formation.
      The isolates were also grown on opposite sides of SDAY agar plates and were
      observed for vegetative compatibility. Neither vegetative compatibility nor
      perithecial stromata could be found to be related to each other. It was concluded
      that fertile fruiting body production was independent of colony pigmentation and
      vegetative compatibility. Synnemata formation was found to be more common than
      perithecial stromata formation. This might be due to its highly conidiogenous
      anamorphic stage, i.e., Beauveria bassiana. 

PMID- 23956639
TI  - Screening of Functional Rhizopus stolonifer for Alcohol Fermentation and
      Production of High Quality Korean Traditional Rice Wine.
AB  - Different strains of mold were screened for the production of high quality Korean
      traditional rice wine with anti-hypertension and good acceptability. We isolated
      867 nuruk mold strains and selected 24 for further study based on measurement of
      amylase activity. Among them, mold No. 17 showed high ethanol production upon
      fermentation with Saccharomyces cerevisiae as well as anti-hypertensive
      properties. The No. 17 strain was therefore selected as the functional mold and
      later identified as Rhizopus stolonifer based on molecular biological
      characteristics. Optimal fermentation conditions for the brewing of anti
      hypertensive traditional rice wine comprised the addition of R. stolonifer No. 17
      koji at a concentration of 35 sp/g and a fermentation period of 10 days at 25C
      using S. cerevisiae. 

PMID- 23956640
TI  - Fruit Body Formation on Silkworm by Cordyceps militaris.
AB  - Injection inoculation protocols for fruit body formation of Cordyceps militaris
      (C. militaris) were investigated to improve the incidence of infection in the
      silkworm species Bombyx mori (B. mori). Injection, with suspensions of C.
      militaris hyphal bodies into living silkworm pupae, was used to test for fruit
      body production. Use of Daeseungjam rather than Baegokjam or Keumokjam varieties
      of B. mori is thought to be suitable for infection by C. militaris. From
      mounting, nine-day-old to 11-day-old pupae showed the best incidence of infection
      with a 100 uL injection volume. Silkworm pupae injected with a hyphal suspension
      concentration of more than 2 * 10(5) colony-forming unit (cfu) recorded a greater
      than 96% incidence of infection. Also, fruit bodies of C. militaris were induced
      and produced at a light intensity between 500 and 1,000 lx. 

PMID- 23956641
TI  - Optimum Conditions for Artificial Fruiting Body Formation of Cordyceps
      cardinalis.
AB  - Stromatal fruiting bodies of Cordyceps cardinalis were successfully produced in
      cereals. Brown rice, German millet and standard millet produced the longest
      length of stromata, followed by Chinese pearl barley, Indian millet, black rice
      and standard barley. Oatmeal produced the shortest-length of fruiting bodies.
      Supplementation of pupa and larva to the grains resulted in a slightly enhanced
      production of fruiting bodies; pupa showing better production than larva. 50~60 g
      of brown rice and 10~20 g of pupa mixed with 50~60 mL of water in 1,000 mL
      polypropylene (PP) bottle was found to be optimum for fruiting body production.
      Liquid inoculation of 15~20 mL per PP bottle produced best fruiting bodies. The
      optimal temperature for the formation of fruiting bodies was 25C, under
      conditions of continuous light. Few fruiting bodies were produced under the
      condition of complete darkness, and the fresh weight was considerable low,
      compared to that of light condition. 

PMID- 23956642
TI  - Optimization of Solid-State Fermentation for Improved Conidia Production of
      Beauveria bassiana as a Mycoinsecticide.
AB  - The production of conidia of entomopathogenic Beauveria bassiana by solid-state
      fermentation was studied for the development of a biocontrol agent against aphid
      Myzus persicae. The optimal conditions for conidia production on polished white
      rice were 40% moisture content, 25C culture temperature, 2-day-old seeding
      culture grown in 3% corn meal, 2% rice bran, 2% corn steep powder medium, initial
      conidia concentration of 10(7) conidia/g in the wet rice, 10% inoculum size, and
      use of a polyethylene bag as a container. The polyethylene bag containing
      inoculated rice was hand-shaken every 12 hr during fermentation. Using optimal
      conditions, the maximum conidia production obtained was 4.05 g conidia/100 g dry
      rice after 14 days of cultivation, a rate 2.83 times higher than conidia yield of
      pre-optimization. 

PMID- 23956643
TI  - Potentiation of Innate Immunity by beta-Glucans.
AB  - beta-Glucans have been known to exhibit antitumor activities by potentiating host
      immunity by an unknown mechanism. The C-type lectin dectin-1, a beta-glucan
      receptor, is found on the macrophage and can recognize various beta-glucans.
      Previously, we demonstrated the presence of beta-glucan receptor, dectin-1, on
      the Raw 264.7 cells as well as on murine mucosal organs, such as the thymus, the
      lung, and the spleen. In order to investigate immunopotentiation of innate
      immunity by beta-glucan, we stimulated a murine macrophage Raw 264.7 cell line
      with beta-glucans from Pleurotus ostreatus, Saccharomyces cerevisiae, and
      Laminaria digitata. Then, we analyzed cytokines such as tumor necrosis factor
      (TNF)-alpha and interleukin (IL)-6 by reverse transcription-polymerase chain
      reaction (RT-PCR). In addition we analyzed gene expression patterns in beta
      glucan-treated Raw 264.7 cells by applying total mRNA to cDNA microarray to
      investigate the expression of 7,000 known genes. When stimulated with beta
      glucans, the macrophage cells increased TNF-alpha expression. When co-stimulation
      of the cells with beta-glucan and lipopolysaccharide (LPS), a synergy effect was
      observed by increased TNF-alpha expression. In IL-6 expression, any of the beta
      glucans tested could not induce IL-6 expression by itself. However, when co
      stimulation occurred with beta-glucan and LPS, the cells showed strong
      synergistic effects by increased IL-6 expression. Chip analysis showed that beta
      glucan of P. ostreatus increased gene expressions of immunomodulating gene
      families such as kinases, lectin associated genes and TNF-related genes in the
      macrophage cell line. Induction of TNF receptor expression by FACS analysis was
      synergized only when co-stimulated with beta-glucan and LPS, not with beta-glucan
      alone. From these data, beta-glucan increased expressions of immunomodulating
      genes and showed synergistic effect with LPS. 

PMID- 23956644
TI  - Notes on the Existence of Leucodecton desquamescens (Thelotremoid Graphidaceae)
      in South Korea.
AB  - This study describes a new record of a thelotremoid lichen (Leucodecton
      desquamescens) from South Korea. The taxon is characterized by thick, bulging
      thallus with many calcium oxalate crystal inclusions; an immersed, round to
      irregular ascomata with free exciple, ellipsoid to +/- roundish submuriform,
      brown ascospores, and lack of secondary metabolites. A detailed taxonomic
      description and comments are presented for this taxon. The lichen genus
      Leucodecton is reported for the first time in South Korea. 

PMID- 23956645
TI  - Production of Ginsenoside-Rg3 from Lipomyces starkeyi Grown on Ginseng-Steaming
      Effluent.
AB  - To produce ginsenoside-Rg3 enriched yeast from ginseng-steaming effluent (GSE),
      Lipomyces starkeyi, which tends to grow well in GSE, was cultured in sterilized
      GSE and its growth and production of ginsenoside-Rg3 were determined. Growth of
      L. starkeyi was 86.1 mg per g GSE and its ginsenoside-Rg3 contents was 0.013 mg
      per g GSE. 

PMID- 23956646
TI  - Stem Rot of Garlic (Allium sativum) Caused by Sclerotium rolfsii.
AB  - Stem rot disease was found in garlic (Allium sativum L.) cultivated from 2008 to
      2010 in the vegetable gardens of some farmers in Geumsan-myon, Jinju City,
      Gyeongnam province in Korea. The initial symptoms of the disease were typical
      water-soaked spots, which progressed to rotting, wilting, blighting, and
      eventually death. White mycelial mats had spread over the lesions near the soil
      line, and sclerotia had formed over the mycelial mats on the stem. The sclerotia
      were globoid in shape, 1~3 mm in size, and tan to brown in color. The optimum
      temperature for growth and sclerotia formation on potato dextrose agar (PDA)
      medium was 30C. The diameter of the hyphae ranged from approximately 4 to 8 um.
      Typical clamp connection structures were observed in the hyphae of the fungus,
      which was grown on PDA medium for 4 days. On the basis of the mycological
      characteristics and pathogenicity of the fungus on the host plants, the causal
      agent was identified as Sclerotium rolfsii Saccardo. This is the first report of
      stem rot disease in garlic caused by S. rolfsii in Korea. 

PMID- 23956647
TI  - Species diversity of hypogeous ascomycetes in Israel.
AB  - We conducted a species diversity study of the hypogeous Ascomycetes of Israel.
      The hypogeous Ascomycetes in Israel include members of the families
      Pyronemataceae, Pezizaceae, and Tuberaceae, which are represented by seven
      species: Hydnocystis piligera, Terfezia arenaria, T. claveryi, T. oligosperma,
      Tirmania africana, Tuber asa, and T. nitidum; only T. asa is new to Israeli
      mycobiota. Synonymy, locations, collection data, general distribution,
      distribution in Israel, descriptions, a key to identification, illustrations, and
      taxonomic remarks are provided. 

PMID- 23956648
TI  - Identification and Characterization of the Causal Organism of Gummy Stem Blight
      in the Muskmelon (Cucumis melo L.).
AB  - Gummy stem blight is a major foliar disease of muskmelon (Cucumis melo L.). In
      this study, morphological characteristics and rDNA internal transcribed spacer
      (ITS) sequences were analyzed to identify the causal organism of this disease.
      Morphological examination of the Jeonbuk isolate revealed that the percentage of
      monoseptal conidia ranged from 0% to 10%, and the average length * width of the
      conidia was 70 (+/- 0.96) * 32.0 (+/- 0.15) um on potato dextrose agar. The BLAST
      analysis showed nucleotide gaps of 1/494, 2/492, and 1/478 with identities of
      485/492 (98%), 492/494 (99%), 491/494 (99%), and 476/478 (99%). The similarity in
      sequence identity between the rDNA ITS region of the Jeonbuk isolate and other
      Didymella bryoniae from BLAST searches of GenBank was 100% and was 95.0% within
      the group. Nucleotide sequences of the rDNA ITS region from pure culture ranged
      from 98.2% to 99.8%. Phylogenetic analysis with related species of D. bryoniae
      revealed that D. bryoniae is a monophyletic group distinguishable from other
      Didymella spp., including Ascochyta pinodes, Mycosphaerella pinodes, M. zeae
      maydis, D. pinodes, D. applanata, D. exigua, D. rabiei, D. lentis, D. fabae, and
      D. vitalbina. Phylogenetic analysis, based on rDNA ITS sequence, clearly
      distinguished D. bryoniae and Didymella spp. from the 10 other species studied.
      This study identified the Jeonbuk isolate to be D. bryoniae. 

PMID- 23956649
TI  - Characteristics of Metacordyceps yongmunensis, a New Species from Korea.
AB  - Metacordyceps yongmunensis is a newly reported species from Korea, which is very
      similar to Cordyceps species in morphological characters. It grows on large
      lepidopteran pupa, and numerous white stromata grow on a single host. Mycelial
      growth characteristics of M. yongmunensis isolates were studied in different
      media and at different temperatures. Also, different carbon sources, nitrogen
      sources, and mineral salts were tested for mycelial growth of M. yongmunensis.
      Schizophyllum (mushroom) genetics complete medium plus yeast extract,
      Schizophyllum (mushroom) genetics minimal medium, and Martin's peptone dextrose
      agar produced longer colony diameters and more compact mycelial density than
      other media. The optimum temperature for mycelial growth was 25C. Carbon sources
      such as sucrose, soluble starch, dextrose, glucose, dextrin, maltose, and
      fructose showed better mycelial growth, whereas peptone, yeast extract and
      tryptone resulted in the best mycelial growth of all of the nitrogen sources
      tested. All of the mineral salts tested showed similar growth as the control,
      except K2HPO4 which showed longer colony diameter and more compact mycelial
      density. The compact colonies were white and cottony with a greenish margin. The
      results showed that M. yongmunensis is an easy fungus to growas it grew from 30
      to more than 50 mm in 2 wk. 

PMID- 23956650
TI  - Plant hormones promote growth in lichen-forming fungi.
AB  - The effect of plant hormones on the growth of lichen-forming fungi (LFF) was
      evaluated. The use of 2,3,5-triiodobenzoic acid and indole-3-butyric acid
      resulted in a 99% and 57% increase in dry weight of the lichen-forming fungus
      Nephromopsis ornata. The results suggest that some plant hormones can be used as
      inducers or stimulators of LFF growth for large-scale culture. 

PMID- 23956651
TI  - Breeding of a Silkworm Variety for Synnemata Production of Isaria tenuipes.
AB  - This study was conducted out to select a silkworm variety suitable for synnemata
      production of Isaria tenuipes. Four kinds of the mulberry silkworm varieties,
      Bombyx mori, were hybridized using a Japanese parental line and a Chinese
      parental line, and used to test for synemata formation in I. tenuipes. The larval
      period of normal silkworms was 22 hr longer than the silkworms inoculated with
      this fungus. Among the silkworm varieties tested, Hachojam had the shortest
      larval period with 23.02 days. The non-cocooning silkworm had a shorter larval
      period than the cocoon producing silkworms. The pupation rate of normal silkworms
      was about 9% higher than that of silkworms sprayed with I. tenuipes. Hachojam had
      the highest infection rate at 99.8%, but no significant difference was observed
      for the infection rate by silkworm variety. The production of synnemata was the
      best in JS171 * CS188 with an incidence rate of 99.3%, followed by Hachojam, and
      Chugangjam. The synnemata produced from Hachojam were the heaviest and showed
      white or milky-white in color. 

PMID- 23956652
TI  - Influence of different supplements on the commercial cultivation of milky white
      mushroom.
AB  - Calocybe indica, known as milky white mushroom, grows and cultivated in the sub
      tropical and temperate zones of South Asia. We investigated the most suitable
      supplements and their levels for the commercial cultivation of milky white
      mushroom. Rice bran, maize powder, and wheat bran with their different levels
      (10, 20, 30, 40, and 50%) were used as supplements to evaluate the yield and
      yield contributing characteristics of C. indica. Primordia initiation was
      observed between 13.5 and 19.3 days. The results indicated that the 30% maize
      powder supplement was effective for producing viable fruiting bodies. The maximum
      diameters of the pileus and stalk were observed with 30% maize powder. The
      highest biological and economic yield and biological efficiency were also
      obtained with 30% maize powder as a supplement. The results indicate that
      increasing the supplement level resulted in less biological efficiency, and that
      30% maize powder was the best supplement level for rice straw substrate to
      cultivate milky white mushrooms. 

PMID- 23956653
TI  - Cultural Characteristics of Shimizuomyces paradoxus Collected from Korea.
AB  - This study investigated the cultural characteristics of Shimizuomyces paradoxus
      in different nutritional and environmental conditions. The highest mycelial
      growth was observed in Schizophyllum (mushroom) genetics complete medium plus
      yeast extract agar medium, and the optimal temperature and pH were 25C and pH
      8.0, respectively. The optimal carbon and nitrogen sources were 1% dextrose and
      1% peptone in agar. However, in liquid culture the highest dry mycelium weight
      was found for the potato dextrose agar and potato sucrose agar broths. The
      optimum inoculum size was five mycelial discs (5 mm) per 100 mL of broth, and the
      optimum liquid culture period was 25 days. This is the first ever report of S.
      paradoxus cultural characteristics. 

PMID- 23956654
TI  - Culture Conditions for Mycelial Growth of Coriolus versicolor.
AB  - Coriolus versicolor, is one of the most popular medicinal mushrooms due its
      various biologically active components. This study was conducted to obtain basic
      information regarding the mycelial culture conditions of C. versicolor. Based on
      the culture, and MCM media were suitable for the mycelial growth of the mushroom.
      The optimum carbon and nitrogen sources were dextrin and yeast extract,
      respectively, and the optimum C/N ratio was 10 to 2 when 2% glucose was used.
      Other minor components required for optimal growth included thiamine-HCl and
      biotin as vitamins, succinic acid, lactic acid and citric acid as organic acids,
      as well as MgSO4.7H2O as mineral salts. 

PMID- 23956655
TI  - Spore Dispersion of Tricholoma matsutake at a Pinus densiflora Stand in Korea.
AB  - The spore of Tricholoma matsutake is considered to be the starting point of the
      mushroom growth cycle, but the mechanism of mycelial development from the spore
      stage is not yet clarified. In this study, we tried to measure how far the spores
      of T. matsutake disperse from a fruiting body located at a Pinus densiflora stand
      in Korea. We established 16 slide glasses coated with glycerin near a fruiting
      body in four directions separated by four different distance intervals within a
      mushroom productive stand after removing all other fruiting bodies from three
      plots. The number of dispersed spores increased with time from the first day (475
      spores/cm(2)) to the fourth day (836 spores/cm(2)) after the pileus opened. The
      number of spores dispersed downward was about 1.5 times greater than that
      dispersed toward the ridge. The number of dispersed spores decreased
      exponentially as the distance from each fruiting body increased. More than 95% of
      the spores dropped within a meter from the fruiting body, with 75% dropping
      within 0.5 m. Even so, the number of spores dispersed over 5 m from the fruiting
      body was more than 50 million when considering the total number of spores
      produced by a fruiting body is about 5 billion. 

PMID- 23956656
TI  - Production of Antihypertensive Angiotensin I-Converting Enzyme Inhibitor-Enriched
      Edible Yeast Using Gugija (Lycium chinesis Mill).
AB  - To produce bioactive compound enriched yeast using medicinal Gugiga (Lycium
      chinensis Mill), several edible Saccharomyces species were cultured in Gugija
      extracts added yeast extract, peptone and dextrose medium (GE - YEPD medium) at
      30C for 24 hr, and their growth were determined. Growth of Saccharomyces
      cerevisiae K-7 and Sacchromyces cerevisiae ACTC 7904 were better than those of
      the other yeasts. Two yeasts were selected and then determined their some
      physiological functionalities after cultivated the yeasts in the GE - YEPD medium
      and compared those grown on YEPD medium. Antihypertensive angiotensin I
      converting enzyme (ACE) inhibitory activity of S. cerevisiae K-7 grown on GE -
      YEPD medium was about 20% higher than that grown on YEPD medium. Superoxide
      dismutase-like activity of S. cerevisiae ACTC 7904 was also about 12% more high.
      However, the other physiological functionalities were almost same or lower.
      Optimal addition concentration of Gugija extract was 10%, and maximally growth
      and ACE inhibitory activity of S. cerevisiae K-7 were shown when the strain was
      cultured in 10% Gugija extracts containing YEPD medium at 30C for 12 hr. 

PMID- 23956657
TI  - Selection of Lecanicillium Strain with High Virulence against Developmental
      Stages of Bemisia tabaci.
AB  - Selection of fungal strains with high virulence against the developmental stages
      of Bemisia tabaci was performed using internal transcribed spacer regions. The
      growth rate of hyphae was measured and bioassay of each developmental stage of B.
      tabaci was conducted for seven days. All of the fungal strains tested were
      identified as Lecanicillium spp., with strain 4078 showing the fastest mycelium
      growth rate (colony diameter, 16.3 +/- 0.9 mm) among the strains. Compared to
      strain 4075, which showed the slowest growth rate, the growth rate of strain 4078
      was increased almost 2-fold after seven days. Strains 4078 and Btab01 were most
      virulent against the egg and larva stages, respectively. The virulence of fungal
      strains against the adult stage was high, except for strains 41185 and 3387.
      Based on the growth rate of mycelium and level of virulence, strains 4078 and
      Btab01 were selected as the best fungal strains for application to B. tabaci,
      regardless of developmental stage. 

PMID- 23956659
TI  - Three new records of lichen genus rhizocarpon from South Korea.
AB  - The paper describes three new records of lichen genus Rhizocarpon (R. alpicola,
      R. grande and R. lavatum) from South Korea. Brief taxonomic description and
      comments are provided for the new records. An artificial key is also provided for
      known species of this genus in South Korea. 

PMID- 23956658
TI  - Identification and Functional Characterization of a Cryptococcus neoformans UPC2
      Homolog.
AB  - Azoles are currently the most widely used class of antifungal drugs clinically,
      and are effective for treating fungal infections. Target site of azoles is
      ergosterol biosynthesis in fungal cell membrane, which is absent in the mammalian
      host. However, the development of resistance to azole treatments in the fungal
      pathogen has become a significant challenge. Here, we report the identification
      and functional characterization of a UPC2 homolog in the human pathogen
      Cryptococcus neoformans. UPC2 plays roles in ergosterol biosynthesis, which is
      also affected by the availability of iron in Saccharomyces cerevisiae and Candida
      albicans. C. neoformans mutants lacking UPC2 were constructed, and a number of
      phenotypic characteristics, including antifungal susceptibility and iron
      utilization, were analyzed. No differences were found between the mutant
      phenotypes and wild type, suggesting that the role of C. neoformans UPC2 homolog
      may be different from those in S. cerevisiae and C. albicans, and that the gene
      may have a yet unknown function. 

PMID- 23956660
TI  - Further additions to lichen genus buellia de not. In South Korea.
AB  - The paper describes two new records of the lichen genus Buellia (B. badia and B.
      nashii) from South Korea. A detailed taxonomic description and comments are
      presented for both taxa. An updated key representing all Buellia species known
      from South Korea is also provided. 

PMID- 23956661
TI  - Variation in Sodium Chloride Resistance of Cenococcum geophilum and Suillus
      granulatus Isolates in Liquid Culture.
AB  - We studied the resistance of Cenococcum geophilum and Suillus granulatus isolates
      to NaCl during growth under axenic culture conditions. C. geophilum isolates
      displayed variations in NaCl resistance; mycelial growth of most isolates was
      inhibited above 200mM. All isolates of S. granulatus were tolerant to high NaCl
      content. 

PMID- 23956662
TI  - Regulation of Development in Aspergillus nidulans and Aspergillus fumigatus.
AB  - Members of the genus Aspergillus are the most common fungi and all reproduce
      asexually by forming long chains of conidiospores (or conidia). The impact of
      various Aspergillus species on humans ranges from beneficial to harmful. For
      example, several species including Aspergillus oryzae and Aspergillus niger are
      used in industry for enzyme production and food processing. In contrast,
      Aspergillus flavus produce the most potent naturally present carcinogen
      aflatoxins, which contaminate various plant- and animal-based foods. Importantly,
      the opportunistic human pathogen Aspergillus fumigatus has become the most
      prevalent airborne fungal pathogen in developed countries, causing invasive
      aspergillosis in immunocompromised patients with a high mortality rate. A.
      fumigatus produces a massive number of small hydrophobic conidia as the primary
      means of dispersal, survival, genome-protection, and infecting hosts. Large-scale
      genome-wide expression studies can now be conducted due to completion of A.
      fumigatus genome sequencing. However, genomics becomes more powerful and
      informative when combined with genetics. We have been investigating the
      mechanisms underlying the regulation of asexual development (conidiation) and
      gliotoxin biosynthesis in A. fumigatus, primarily focusing on a characterization
      of key developmental regulators identified in the model fungus Aspergillus
      nidulans. In this review, I will summarize our current understanding of how
      conidiation in two aspergilli is regulated. 

PMID- 23956663
TI  - Environmental factors and bioremediation of xenobiotics using white rot fungi.
AB  - This review provides background information on the importance of bioremediation
      approaches. It describes the roles of fungi, specifically white rot fungi, and
      their extracellular enzymes, laccases, ligninases, and peroxidises, in the
      degradation of xenobiotic compounds such as single and mixtures of pesticides. We
      discuss the importance of abiotic factors such as water potential, temperature,
      and pH stress when considering an environmental screening approach, and examples
      are provided of the differential effect of white rot fungi on the degradation of
      single and mixtures of pesticides using fungi such as Trametes versicolor and
      Phanerochaete chrysosporium. We also explore the formulation and delivery of
      fungal bioremedial inoculants to terrestrial ecosystems as well as the use of
      spent mushroom compost as an approach. Future areas for research and potential
      exploitation of new techniques are also considered. 

PMID- 23956664
TI  - Identification of Lacrymaria velutina (Pers. Ex Fr.) Konrad & Maubl. from Micheon
      myeon, Jinju-city, Korea.
AB  - We identified Lacrymaria velutina of the Coprinaceae in Korea. The unusually
      large and sturdy fruiting body, fibrillose to fibrillose-scaly cap and stalk
      without a volva with an obscure superior hairy ring zone or hairy annulus, and
      blackish brown, warted spores distinguished this species from closely related
      Psathyrella species. An illustrated account of the microscopic traits is
      presented. Fruiting bodies with obtusely hemispherical caps, 2.5~6 cm, becoming
      convex with age; surface dry, densely fibrillose-scaly with split margin; stipe,
      4.5~6 cm, equal, hollow, fibrillose, dry, whitish above the superior ring zone,
      light brown below; crowded gills, adnexed, dark black at maturity. Pileipellis
      typically cellular with the gill edge appearing white and beaded. Blackish brown
      basidiospores that discolor in concentrated sulfuric acid. Spores elliptical,
      warted, 9~11 * 6~8 um, with prominent snout-like germpores. Cheilocystidia
      abundant, 57~68 * 19~25 um, and narrowly elongated clavate, often clustered in
      threes or fours. Pleurocystidia rarely present, 45~47.5 * 12~13 um, and clavate
      to utriform. This trait distinguishes our sample as L. velutina from other
      Psathyrella spp. of the Coprinaceae, which have smooth spores. This taxon was
      clarified by the observation that Psathyrella spores fade in concentrated
      sulfuric acid. A molecular phylogenetic study revealed that our specimen was
      Lacrymria velutipes, which is closely related to Lacrymaria lacrymabunda.
      Moreover, those two species are clearly distinguishable from other Psathyrella
      species, which agreed with the morphologically distinctive traits described
      above. We believe that this is the first report of this taxon, which has not been
      described in Korea. 

PMID- 23956665
TI  - Checklist of hymenomycetes (aphyllophorales s.L.) and heterobasidiomycetes in
      Israel.
AB  - A checklist is presented concerning the species composition of Hymenomycetes
      (Aphyllophorales s.l.) and Heterobasidiomycetes in Israel based on data of
      previous studies and field sample collections. In total, 242 species are
      presented, of which five are new records for the Israeli mycobiota, namely
      Australohydnum dregeanum, Ceriporiopsis consobrina, C. resinascens, Fibroporia
      vaillantii, and Postia inocybe. The distribution and habitat of each species in
      Israel are also summarized. This checklist will serve as valuable data for future
      species diversity studies of these fungi in Israel. 

PMID- 23956666
TI  - Growth and Cultural Characteristics of Cordyceps cardinalis Collected from Korea.
AB  - Cordyceps cardinalis was reported in Japan and the USA in 2004, and its fruiting
      bodies have recently been cultured in Korea. Herbarium specimens preserved at the
      Cordyceps Research Institute, Mushtech, Korea were revised and identified as C.
      cardinalis, based on morphological characters and conidial structures. Most of
      the C. cardinalis specimens were collected from Mt. Halla in Jeju-do. The effects
      of various nutritional sources and environmental conditions such as temperature
      and pH on mycelial growth of C. cardinalis were studied. Oatmeal agar, Martin's
      peptone dextrose agar, and Schizophyllum (mushroom) genetics complete medium plus
      yeast extract resulted in the best mycelial growth. Among carbon sources,
      cereals, and nitrogen sources, maltose, oatmeal, and peptone resulted in the best
      mycelial growth respectively. Mineral salts helped to increase growth rate but
      only resulted in thin mycelial density, similar to water agar. A temperature of
      25C and a pH of 7 resulted in the highest mycelial growth. Based on these
      results, a Cordyceps cardinalis composite medium (CCM) was formulated with 1%
      maltose, 2% oatmeal, 1% peptone, and 2% agar. Use of the CCM resulted in slightly
      better mycelial growth than that of other commonly used agar media. Only organic
      nitrogen sources imparted a reddish pigmentation to the agar media, but this
      character diminished after several subcultures. A 7 day culture duration resulted
      in the best mycelial growth. 

PMID- 23956667
TI  - Heterothallic Type of Mating System for Cordyceps cardinalis.
AB  - Cordyceps cardinalis successfully produced its fruiting bodies from multi
      ascospore isolates. However, subcultures of multi-ascospore isolates could not
      produce fruiting bodies after few generations. Fruiting body production also
      differed from sector to sector of the same isolate. Single ascospore isolates
      were then co-inoculated in combinations of two to observe the fruiting
      characteristics. Combinations of certain isolates produced perithecial stromata
      formation, whereas other combinations did not produce any fruiting bodies. These
      results show that C. cardinalis is a heterothallic fungus, requiring two isolates
      of opposite mating types for fruiting body production. It was also shown that
      single ascospore isolates are hermaphrodites. 

PMID- 23956668
TI  - Potential of Epicoccum purpurascens Strain 5615 AUMC as a Biocontrol Agent of
      Pythium irregulare Root Rot in Three Leguminous Plants.
AB  - Epicoccum purpurascens stain 5615 AUMC was investigated for its biocontrol
      activity against root rot disease caused by Pythium irregulare. E. purpurascens
      greenhouse pathogenicity tests using three leguminous plants indicated that the
      fungus was nonpathogenic under the test conditions. The germination rate of the
      three species of legume seeds treated with a E. purpurascens homogenate increased
      significantly compared with the seeds infested with P. irregulare. No root rot
      symptoms were observed on seeds treated with E. purpurascens, and seedlings
      appeared more vigorous when compared with the non-treated control. A significant
      increase in seedling growth parameters (seedling length and fresh and dry
      weights) was observed in seedlings treated with E. purpurascens compared to
      pathogen-treated seedlings. Pre-treating the seeds with the bioagent fungus was
      more efficient for protecting seeds against the root rot disease caused by P.
      irregulare than waiting for disease dispersal before intervention. To determine
      whether E. purpurascens produced known anti-fungal compounds, an acetone extract
      of the fungus was analyzed by gas chromatography mass spectrometry. The extract
      revealed a high percentage of the cinnamic acid derivative (trimethylsiloxy)
      cinnamic acid methyl ester. The E. purpurascens isolate grew more rapidly than
      the P. irregulare pathogen in a dual culture on potato dextrose agar nutrient
      medium, although the two fungi grew similarly when cultured separately. This
      result may indicate antagonism via antibiosis or competition. 

PMID- 23956669
TI  - Antioxidant Activities and Tyrosinase Inhibitory Effects of Different Extracts
      from Pleurotus ostreatus Fruiting Bodies.
AB  - We evaluated the antioxidant activity and tyrosinase inhibitory effects of
      Pleurotus ostreatus fruiting bodies extracted with acetone, methanol, and hot
      water. The antioxidant activities were tested against beta-carotene-linoleic
      acid, reducing power, 1,1-diphenyl-2-picrylhydrazyl free radical scavenging
      activity, and ferrous chelating ability. Furthermore, phenolic acid and flavonoid
      contents were also analyzed. The methanol extract showed the strongest beta
      carotene-linoleic acid inhibition as compared to the other exracts. The acetone
      extract (8 mg/mL) showed a significantly high reducing power of 1.54 than the
      other extracts. The acetone extract was more effective than other extracts for
      scavenging on 1,1-diphenyl-2-picrylhydrazyl radicals. The strongest chelating
      effect (85.66%) was obtained from the acetone extract at 1.0 mg/mL. The
      antioxidant activities of the extracts from the P. ostreatus fruiting bodies
      increased with increasing concentration. A high performance liquid chromatography
      analysis detected seven phenolic compounds, including gallic acid, protocatechuic
      acid, chlorogenic acid, naringenin, hesperetin, formononetin, and biochanin-A in
      an acetonitrile and 0.1 N hydrochloric acid (5: 1) solvent extract. The total
      phenolic compound concentration was 188 ug/g. Tyrosinase inhibition of the
      acetone, methanol, and hot water P. ostreatus extracts increased with increasing
      concentration. The results revealed that the methanol extract had good tyrosinase
      inhibitory ability, whereas the acetone and hot water extracts showed moderate
      activity at the concentrations tested. The results suggested that P. ostreatus
      may have potential as a natural antioxidant. 

PMID- 23956670
TI  - Proteomic Evaluation of Cellular Responses of Saccharomyces cerevisiae to Formic
      Acid Stress.
AB  - Formic acid is a representative carboxylic acid that inhibits bacterial cell
      growth, and thus it is generally considered to constitute an obstacle to the
      reuse of renewable biomass. In this study, Saccharomyces cerevisiae was used to
      elucidate changes in protein levels in response to formic acid. Fifty-seven
      differentially expressed proteins in response to formic acid toxicity in S.
      cerevisiae were identified by 1D-PAGE and nano-liquid chromatography-tandem mass
      spectrometry (nano-LC-MS/MS) analyses. Among the 28 proteins increased in
      expression, four were involved in the MAP kinase signal transduction pathway and
      one in the oxidative stress-induced pathway. A dramatic increase was observed in
      the number of ion transporters related to maintenance of acid-base balance.
      Regarding the 29 proteins decreased in expression, they were found to participate
      in transcription during cell division. Heat shock protein 70, glutathione
      reductase, and cytochrome c oxidase were measured by LC-MS/MS analysis. Taken
      together, the inhibitory action of formic acid on S. cerevisiae cells might
      disrupt the acid-base balance across the cell membrane and generate oxidative
      stress, leading to repressed cell division and death. S. cerevisiae also induced
      expression of ion transporters, which may be required to maintain the acid-base
      balance when yeast cells are exposed to high concentrations of formic acid in
      growth medium. 

PMID- 23956671
TI  - Isolation and Identification of Mushroom Pathogens from Agrocybe aegerita.
AB  - Agrocybe aegerita is an important mushroom cultivated in Korea, with good feel
      and a peculiar fragrance. A. aegerita can be cultivated throughout the year using
      culture bottles but is more susceptible to contamination than other mushrooms.
      Twenty-two pathogens were isolated from the fruiting bodies and compost of A.
      aegerita, and seven isolates were isolated from Pleurotus ostreatus to compare
      with the A. aegerita isolates, collected from Gimje, Iksan, Gunsan of Chonbuk,
      and Chilgok of Gyeongbuk Province in 2009. These isolates were identified based
      on morphological and molecular characteristics. Of the 29 isolates, 26 were
      identified as Trichoderma spp. and the remaining three were Aspergillus spp.,
      Mucor spp., and Penicillium spp. A phylogenetic analysis revealed that the 26
      isolates of Trichoderma were divided into four taxa, namely T. harzianum, T.
      pleuroticola, T. longibrachiatum, and T. atroviride. Among the Trichoderma spp.,
      16 isolates (55.2%) were identified as T. harzianum, six as T. pleuroticola
      (20.7%), two as T. longibrachiatum, and the remaining two were T. atroviride. 

PMID- 23956672
TI  - First Report of Foliar Blight on Dendropanax morbifera Caused by Alternaria
      panax.
AB  - Leaf spot and blight disease was observed on two-year-old seedlings of
      Dendropanax morbifera (Korean name: Hwangchil tree) during July of 2008 in Jindo
      Island, Korea. Symptoms included yellow-brown to dark brown irregularly enlarged
      spots frequently located along the veins of leaves. The lesions were often
      surrounded by chlorotic haloes. Severe leaf blight and subsequent defoliation
      occurred when conditions favored disease outbreak. The causal organism of the
      disease was identified as Alternaria panax based on morphological characteristics
      and sequence analysis of the internal transcribed spacer region of rDNA. A. panax
      isolates induced leaf spots and blight symptoms not only on D. morbifera but also
      on the other members of Araliaceae tested. This is the first report of foliar
      blight caused by A. panax on D. morbifera. 

PMID- 23956673
TI  - Dactylospora glaucomarioides (Ascomycetes, Dactylosporaceae): A Lichenicolous
      Fungus New to South Korea.
AB  - The lichenicolous fungi flora of South Korea is poorly known. During recent field
      trips to various parts of South Korea and after an extensive examination of
      herbarium lichen specimens, we encountered a lichenicolous fungi growing over a
      thallus of the lichen Ochrolechia yasudae Vain., characterized by small black
      apothecia with mostly three-septate brown ascospores. It was identified as
      Dactylospora glaucomarioides. This is the first report of this lichenicolous
      fungus from South Korea. A taxonomic description and comments are presented. 

PMID- 23956674
TI  - Notes on some new species of psathyrella.
AB  - This study contains descriptions and illustrations of three new and noteworthy
      taxa of the genus Psathyrella from Korea. Among them, Psathyrella pervelatoid, P.
      koreana, and P. utriformcystis are new to science. All collections cited here are
      deposited in the Herbarium Conservation Center of National Academy of
      Agricultural Sciences. 

PMID- 23956675
TI  - In Vitro Antifungal Activity of Equol against Candida albicans.
AB  - In this study, we demonstrate that equol has fungicidal activities against
      Candida albicans. The minimum inhibitory and minimum fungicidal concentrations of
      equol against C. albicans were 516 and 1,032 uM, respectively. Two separate
      viability assays found that equol changed the integrity of the C. albicans cell
      membrane, possibly by formation of membrane lesions. Scanning electron microscopy
      demonstrated ultrastructural changes. 

PMID- 23956676
TI  - Highly Efficient Electroporation-mediated Transformation into Edible Mushroom
      Flammulina velutipes.
AB  - In this study, we developed an efficient electroporation-mediated transformation
      system featuring Flammulina velutipes. The flammutoxin (ftx) gene of F. velutipes
      was isolated by reverse transcription-PCR. pFTXHg plasmid was constructed using
      the partial ftx gene (410 bp) along with the hygromycin B phosphotransferase gene
      (hygB) downstream of the glyceraldehydes-3-phosphate dehydrogenase (gpd)
      promoter. The plasmid was transformed into protoplasts of monokaryotic strain
      4019-20 of F. velutipes by electroporation. High transformation efficiency was
      obtained with an electric-pulse of 1.25 kV/cm by using 177 transformants/ug of
      DNA in 1 * 10(7) protoplasts. PCR and Southern blot hybridization indicated that
      a single copy of the plasmid DNA was inserted at different locations in the F.
      velutipes genome by non-homologous recombination. Therefore, this transformation
      system could be used as a useful tool for gene function analysis of F. velutipes.

PMID- 23956677
TI  - Soft Rot on Cucumis melo var. makuwa Caused by Rhizopus oryzae.
AB  - Rhizopus oryzae is reported for the first time on Cucumis melo L. var. makuwa
      Makino. A detailed description of this Korean specimen is given, along with its
      rDNA internal transcribed spacer sequence. On the basis of mycological
      characteristics and molecular data, the fungus was identified as R. oryzae Went &
      Prinsen Geerligs. 

PMID- 23956678
TI  - Identification of Calonectria colhounii Associated with Basal Stem Rot on
      Blueberry Seedlings Imported from the United States of America.
AB  - Basal stem rot symptoms were found on blueberry seedlings imported from the
      United States of America in 2008. The fungus obtained from the diseased seedlings
      was identified as Calonectria colhounii based on morphological and molecular
      characteristics. The consignments of the blueberry seedlings infected with C.
      colhounii were destroyed to prevent introduction of the fungus to Korea. 

PMID- 23956679
TI  - Changes to indoor air quality as a result of relocating families from slums to
      public housing.

PMID- 23956680
TI  - Osteosarcoma: A Comparison of Jaw versus Nonjaw Localizations and Review of the
      Literature.
AB  - Purpose. It is assumed that osteosarcomas of the jaws mainly occur at older ages,
      whereas the most prominent sites, that is, the long bones, are more affected at
      ages <20. Jaw-localized tumors are less malignant and have lower metastatic
      spread rates. Patients and Methods. This study analyses the nationwide data of
      the Dutch Cancer Registry on osteosarcoma during the period from 1991 to 2010.
      Age-corrected incidence rates were calculated. Results. In 949, 38 patients had
      tumors in the maxilla and in 58 in the mandible. Median age for maxilla,
      mandible, and other localizations was 45.5, 49, and 23 years, respectively. Age
      corrected incidence for osteosarcomas increased after a steep decline for the age
      cohorts from 20 to 60 years to nearly the same level as the younger patients. The
      incidence for maxillary lesions showed a steady increase from 0.46 to 1.60 per
      million over all age ranges; the highest incidence for mandibular lesions was
      found in the age cohort from 60 to 79 years. In respect to histology, no shifts
      for age were found, except for Paget's disease-related osteosarcoma. In older
      patients, chemotherapy was omitted more often. Overall survival was similar for
      all age groups, except for extragnatic tumor patients in the age range of 60-79
      years. Conclusions. Osteosarcomas have comparable incidences below the age of 20
      as compared with ages >60 years. Poorer outcome in older people is likely due to
      refraining from chemotherapy. 

PMID- 23956681
TI  - Reproducible culture and differentiation of mouse embryonic stem cells using an
      automated microwell platform.
AB  - The use of embryonic stem cells (ESCs) and their progeny in high throughput drug
      discovery and regenerative medicine will require production at scale of well
      characterized cells at an appropriate level of purity. The adoption of automated
      bioprocessing techniques offers the possibility to overcome the lack of
      consistency and high failure rates seen with current manual protocols. To build
      the case for increased use of automation this work addresses the key question:
      "can an automated system match the quality of a highly skilled and experienced
      person working manually?" To answer this we first describe an integrated
      automation platform designed for the 'hands-free' culture and differentiation of
      ESCs in microwell formats. Next we outline a framework for the systematic
      investigation and optimization of key bioprocess variables for the rapid
      establishment of validatable Standard Operating Procedures (SOPs). Finally the
      experimental comparison between manual and automated bioprocessing is exemplified
      by expansion of the murine Oct-4-GiP ESC line over eight sequential passages with
      their subsequent directed differentiation into neural precursors. Our results
      show that ESCs can be effectively maintained and differentiated in a highly
      reproducible manner by the automated system described. Statistical analysis of
      the results for cell growth over single and multiple passages shows up to a 3
      fold improvement in the consistency of cell growth kinetics with automated
      passaging. The quality of the cells produced was evaluated using a panel of
      biological markers including cell growth rate and viability, nutrient and
      metabolite profiles, changes in gene expression and immunocytochemistry.
      Automated processing of the ESCs had no measurable negative effect on either
      their pluripotency or their ability to differentiate into the three embryonic
      germ layers. Equally important is that over a 6-month period of culture without
      antibiotics in the medium, we have not had any cases of culture contamination.
      This study thus confirms the benefits of adopting automated bioprocess routes to
      produce cells for therapy and for use in basic discovery research.

PMID- 23956682
TI  - Organometallic cis-Dichlorido Ruthenium(II) Ammine Complexes.
AB  - Bifunctional neutral half-sandwich RuII complexes of the type [(eta6
      arene)Ru(NH3)Cl2] where arene is p-cym (1) or bip (2) were synthesised by the
      reaction of N,N-dimethylbenzylamine (dmba), NH4PF6 and the corresponding RuII
      arene dimer, and were fully characterised. X-ray crystallographic studies of
      [(eta6-p-cym)Ru(NH3)Cl2].{(dmba-H)(PF6)} (1a) and [(eta6-bip)Ru(NH3)Cl2] (2) show
      extensive H-bond interactions in the solid state, mainly involving the NH3 and
      the Cl ligands, as well as weak aromatic stacking interactions. The half-lives
      for the sequential hydrolysis of 1 and 2 determined by UV/Vis spectroscopy at 310
      K ranged from a few minutes for the first aquation to ca. 45 min for the second
      aquation; the diaqua adducts were the predominant species at equilibrium. Arene
      loss during the aquation of complex 2 was observed. Upon hydrolysis, both
      complexes readily formed mono- and di-9-ethylguanine (9-EtG) adducts in aqueous
      solution at 310 K. The reaction reached equilibrium after ca. 1.8 h in the case
      of complex 1 and was slower but more complete for complex 2 (before the onset of
      arene loss at ca. 2.7 h). Complexes 1 and 2 were not cytotoxic towards A2780
      human ovarian cancer cells up to the maximum concentration tested (100 MUM).

PMID- 23956683
TI  - A Valence Bond Description of Dizwitterionic Dithiolene Character in an
      Oxomolybdenum-bis(dithione).
AB  - Metallo-dithiolene non-innocence is explored in an oxomolybdenum-bis(dithione)
      complex, [Mo4+O(i-Pr2Pipdt)2Cl][PF6] (where i-Pr2Pipdt is N,N'-piperazine-2,3
      dithione), that possesses a piperazine ring as an integral part of the dithiolene
      ligand. The title complex displays unusual spectroscopic features for a formally
      reduced Mo(IV) dithiolene complex, namely a low energy metal-to-ligand charge
      transfer band with appreciable intensity and C-C and C-S stretching frequencies
      that are markedly different from those of oxomolydenum complexes coordinated to
      dianionic dithiolene ligands. The electronic structure of the ligand has been
      described in valence bond terms as a resonance hybrid of dithione and
      dizwitterionic dithiolene contributing structures.

PMID- 23956684
TI  - Synthesis of C2 -Symmetric Dimeric Re(I) Peptide Complexes.
AB  - The reactions of [Re(CO)3(H2O)3]Br or Re(CO)5Cl with two peptides, glycylglycine
      or glycylalanine, were investigated. Each reaction produced a unique, well
      defined product. Structural elucidation showed the formation of chiral compounds
      with the formula [Re(CO)3(Gly-Xxx-O)]2, Xxx = Gly 1, Ala 2. Each dimer displays
      C2 -symmetry and a nearly rectangular shape. The ligands are bound via the amine
      and amide carbonyl at a rhenium center and via the pendant carboxylate to the
      adjacent rhenium center. Both products are fully characterized, via X-ray
      structure elucidation.

PMID- 23956685
TI  - Self-report of illicit substance use versus urine toxicology results from at-risk
      pregnant women.
AB  - INTRODUCTION: Many factors comprise a patient's decision to disclose use of
      drugs. Pregnant women may report drug use because they would like help with their
      addiction but the stigma associated with drug use may dampen their willingness to
      disclose. Knowledge about the accuracy of self-reported drug use as compared to
      urine toxicology screens can assist clinicians in the management of substance use
      in pregnancy. METHOD: We compared the urine toxicology screens and self-reported
      use of marijuana or cocaine for 168 women enrolled in an integrated
      obstetrical/substance abuse treatment program. We stratified by various periods
      of self-reported use and race and utilized Cohen's kappa to measure overall
      agreement between self-report and toxicology tests. RESULTS: Most women with a
      positive toxicology screen reported use in the past 28 days (78% for marijuana,
      86% for cocaine). However, many women reported their most recent use to be
      outside of the assays' detection window (14% for marijuana, 57% for cocaine). We
      did not find differences in self-report for women with positive urine between
      Whites and non-Whites (p = 1.00). Agreement over the previous month was good
      (Kappa = 0.74 and 0.70 for marijuana and cocaine, respectively.). SUMMARY: A
      question about use of marijuana or cocaine during the preceding month rather than
      the prior few days may be a better indicator of use.

PMID- 23956686
TI  - What Happened to the Wages of Mexican Immigrants? Trends and Interpretations.
AB  - Over the past several decades the wages earned by Mexican immigrants stagnated
      relative to those earned by native Mexican Americans and non-Hispanic whites. In
      this article we draw on data from the decennial census and American Community
      Survey to understand why and how this stagnation occurred. We test two competing
      explanations: a decline in the quality of successive cohorts of Mexican
      immigrants and a shift in the political economy that increased the number of
      people lacking full labor rights in the United States while increasing
      discrimination and exclusion against such people. We present evidence in favor of
      the latter explanation by showing that observed quality increased rather than
      decreased and that what happened instead was a systematic decline in the returns
      to various measures of human capital and a wholesale drop in wages for all
      immigrants after 2000.

PMID- 23956687
TI  - Correction.

PMID- 23956688
TI  - Host Lipid and Temperature as Important Screening Variables for Crystallizing
      Integral Membrane Proteins in Lipidic Mesophases. Trials with Diacylglycerol
      Kinase.
AB  - A systematic study of the crystallization of an alpha-helical, integral membrane
      enzyme, diacylglycerol kinase, DgkA, using the lipidic cubic mesophase or in meso
      method is described. These trials have resulted in the production of blocky,
      rhombohedron-shaped crystals of diffraction quality currently in use for
      structure determination. Dramatic improvements in crystal quality were obtained
      when the identity of the lipid used to form the mesophase bilayer into which the
      protein was reconstituted as a prelude to crystallogenesis was varied. These
      monoacylglycerol lipids incorporated fatty acyl chains ranging from 14 to 18
      carbon atoms long with cis olefinic bonds located toward the middle of the chain.
      Best crystals were obtained with a lipid that had an acyl chain 15 carbon atoms
      long with the double bond between carbons 7 and 8. It is speculated that the
      effectiveness of this lipid derives from hydrophobic mismatch between the target
      integral membrane protein and the bilayer of the host mesophase. Low temperature
      (4  degrees C) worked in concert with the short chain lipid to provide high
      quality crystals. Recommended screening strategies for crystallizing membrane
      proteins that include host lipid type and low temperature are made on the basis
      of this and related in meso crystallization trials.

PMID- 23956689
TI  - An augmented classical least squares method for quantitative Raman spectral
      analysis against component information loss.
AB  - We propose an augmented classical least squares (ACLS) calibration method for
      quantitative Raman spectral analysis against component information loss. The
      Raman spectral signals with low analyte concentration correlations were selected
      and used as the substitutes for unknown quantitative component information during
      the CLS calibration procedure. The number of selected signals was determined by
      using the leave-one-out root-mean-square error of cross-validation (RMSECV)
      curve. An ACLS model was built based on the augmented concentration matrix and
      the reference spectral signal matrix. The proposed method was compared with
      partial least squares (PLS) and principal component regression (PCR) using one
      example: a data set recorded from an experiment of analyte concentration
      determination using Raman spectroscopy. A 2-fold cross-validation with Venetian
      blinds strategy was exploited to evaluate the predictive power of the proposed
      method. The one-way variance analysis (ANOVA) was used to access the predictive
      power difference between the proposed method and existing methods. Results
      indicated that the proposed method is effective at increasing the robust
      predictive power of traditional CLS model against component information loss and
      its predictive power is comparable to that of PLS or PCR. 

PMID- 23956690
TI  - Insights gained from P. falciparum cultivation in modified media.
AB  - In vitro cultivation of Plasmodium falciparum, the agent of severe human malaria,
      has enabled advances in basic research and accelerated the development of new
      therapies. Since the introduction of in vitro parasite culture nearly 40 years
      ago, most workers have used a medium consisting of RPMI 1640 medium supplemented
      with lipids and hypoxanthine. While these standardized conditions yield robust
      parasite growth and facilitate comparison of results from different studies, they
      may also lead to implicit assumptions that limit future advances. Here, I review
      recent studies that used modified culture conditions to challenge these
      assumptions and explore parasite physiology. The findings are relevant to
      understanding in vivo parasite phenotypes and the prioritization of antimalarial
      targets. 

PMID- 23956691
TI  - Numerical investigation of entropy generation in unsteady MHD generalized Couette
      flow with variable electrical conductivity.
AB  - The thermodynamic second law analysis is utilized to investigate the inherent
      irreversibility in an unsteady hydromagnetic generalized Couette flow with
      variable electrical conductivity in the presence of induced electric field. Based
      on some simplified assumption, the model nonlinear governing equations are
      obtained and solved numerically using semidiscretization finite difference
      techniques. Effects of various thermophysical parameters on the fluid velocity,
      temperature, current density, skin friction, the Nusselt number, entropy
      generation number, and the Bejan number are presented graphically and discussed
      quantitatively. 

PMID- 23956692
TI  - Plasma clusterin concentrations may predict resistance to intravenous
      immunoglobulin in patients with Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute febrile vasculitic syndrome of early childhood
      often complicated by coronary artery lesion that drastically reduces the quality
      of life. The study aimed to identify a reliable marker for predicting
      nonresponsiveness to the first course of intravenous immunoglobulin (IVIG) in KD
      patients. A total of 63 patients with KD were enrolled in the study (IVIG
      response, 58; IVIG resistance, 5). Plasma samples were collected before and after
      IVIG infusion for measurement of biomarkers. Patients' clinical characteristics
      and laboratory data were also analyzed. A receiver operating characteristic curve
      was generated to identify a cut-off value for predicting IVIG resistance. Among
      the biomarkers, the difference in plasma clusterin concentrations before and
      after IVIG infusion (CLUSTER 12) was significantly related to IVIG resistance (P
      = 0.040; 95% confidence interval (CI): -25.8% to -6.0%). Using a CLUSTER 12 cut
      off value of <8.52 mg/L, the odds ratio for IVIG resistance was 11.467 (95% CI:
      1.186 to 110.853). Patients with plasma CLUSTER 12 concentrations >8.52 mg/L had
      a much higher risk of IVIG resistance than those with CLUSTER 12 concentrations
      <8.52 mg/L. Plasma clusterin concentration shows promise as a candidate biomarker
      for predicting IVIG resistance in patients with KD.

PMID- 23956693
TI  - PRESEE: an MDL/MML algorithm to time-series stream segmenting.
AB  - Time-series stream is one of the most common data types in data mining field. It
      is prevalent in fields such as stock market, ecology, and medical care.
      Segmentation is a key step to accelerate the processing speed of time-series
      stream mining. Previous algorithms for segmenting mainly focused on the issue of
      ameliorating precision instead of paying much attention to the efficiency.
      Moreover, the performance of these algorithms depends heavily on parameters,
      which are hard for the users to set. In this paper, we propose PRESEE (parameter
      free, real-time, and scalable time-series stream segmenting algorithm), which
      greatly improves the efficiency of time-series stream segmenting. PRESEE is based
      on both MDL (minimum description length) and MML (minimum message length)
      methods, which could segment the data automatically. To evaluate the performance
      of PRESEE, we conduct several experiments on time-series streams of different
      types and compare it with the state-of-art algorithm. The empirical results show
      that PRESEE is very efficient for real-time stream datasets by improving
      segmenting speed nearly ten times. The novelty of this algorithm is further
      demonstrated by the application of PRESEE in segmenting real-time stream datasets
      from ChinaFLUX sensor networks data stream. 

PMID- 23956694
TI  - How can stress be controlled in endodontically treated teeth? A 3D finite element
      analysis.
AB  - The aim of this study was to analyze the stresses that develop by oblique and
      vertical forces in endodontically treated maxillary second premolars that were
      restored with resin composite. Additionally, in our study the effects of the
      different restorative approaches and use of different base materials on stress
      formation were analyzed using three-dimensional finite element stress analysis.
      For restoration, the models representing both cusp capping, palatinal cusp
      capping, standard MOD restoration, and use of woven fiber in occlusal part were
      prepared. In all models, oblique forces caused more stress than did vertical
      forces. Materials with low elastic moduli cause high amounts of stress, whereas
      materials with elastic moduli similar to that of dental tissues cause low amounts
      of stress. Additional approaches such as cusp capping, functional cusp capping,
      and woven fiber use do not affect stress formation on the tooth after endodontic
      treatment. 

PMID- 23956695
TI  - Evaluation of correlations of flow boiling heat transfer of R22 in horizontal
      channels.
AB  - The calculation of two-phase flow boiling heat transfer of R22 in channels is
      required in a variety of applications, such as chemical process cooling systems,
      refrigeration, and air conditioning. A number of correlations for flow boiling
      heat transfer in channels have been proposed. This work evaluates the existing
      correlations for flow boiling heat transfer coefficient with 1669 experimental
      data points of flow boiling heat transfer of R22 collected from 18 published
      papers. The top two correlations for R22 are those of Liu and Winterton (1991)
      and Fang (2013), with the mean absolute deviation of 32.7% and 32.8%,
      respectively. More studies should be carried out to develop better ones. Effects
      of channel dimension and vapor quality on heat transfer are analyzed, and the
      results provide valuable information for further research in the correlation of
      two-phase flow boiling heat transfer of R22 in channels. 

PMID- 23956696
TI  - Marine renewable energies: perspectives and implications for marine ecosystems.

PMID- 23956697
TI  - The hydrolysis of carbonyl sulfide at low temperature: a review.
AB  - Catalytic hydrolysis technology of carbonyl sulfide (COS) at low temperature was
      reviewed, including the development of catalysts, reaction kinetics, and reaction
      mechanism of COS hydrolysis. It was indicated that the catalysts are mainly
      involved metal oxide and activated carbon. The active ingredients which can load
      on COS hydrolysis catalyst include alkali metal, alkaline earth metal, transition
      metal oxides, rare earth metal oxides, mixed metal oxides, and nanometal oxides.
      The catalytic hydrolysis of COS is a first-order reaction with respect to
      carbonyl sulfide, while the reaction order of water changes as the reaction
      conditions change. The controlling steps are also different because the reaction
      conditions such as concentration of carbonyl sulfide, reaction temperature, water
      air ratio, and reaction atmosphere are different. The hydrolysis of carbonyl
      sulfide is base-catalyzed reaction, and the force of the base site has an
      important effect on the hydrolysis of carbonyl sulfide. 

PMID- 23956698
TI  - Cascadable current-mode first-order all-pass filter based on minimal components.
AB  - A novel current-mode first-order all-pass filter with low input and high output
      impedance feature is presented. The circuit realization employs a single dual-X
      second-generation current conveyor, one grounded capacitor, and one grounded
      resistor, which is a minimum component realization. The theoretical results are
      verified using PSPICE simulation program with TSMC 0.35 MUm CMOS process
      parameters.

PMID- 23956699
TI  - An innovative thinking-based intelligent information fusion algorithm.
AB  - This study proposes an intelligent algorithm that can realize information fusion
      in reference to the relative research achievements in brain cognitive theory and
      innovative computation. This algorithm treats knowledge as core and information
      fusion as a knowledge-based innovative thinking process. Furthermore, the five
      key parts of this algorithm including information sense and perception, memory
      storage, divergent thinking, convergent thinking, and evaluation system are
      simulated and modeled. This algorithm fully develops innovative thinking skills
      of knowledge in information fusion and is a try to converse the abstract
      conception of brain cognitive science to specific and operable research routes
      and strategies. Furthermore, the influences of each parameter of this algorithm
      on algorithm performance are analyzed and compared with those of classical
      intelligent algorithms trough test. Test results suggest that the algorithm
      proposed in this study can obtain the optimum problem solution by less target
      evaluation times, improve optimization effectiveness, and achieve the effective
      fusion of information. 

PMID- 23956700
TI  - Building Evidence for Evidence-Based Policy Making.

PMID- 23956701
TI  - Iterative Molecular Dynamics-Rosetta Protein Structure Refinement Protocol to
      Improve Model Quality.
AB  - Rosetta is one of the prime tools for high resolution protein structure
      refinement. While its scoring function can distinguish native-like from non
      native-like conformations in many cases, the method is limited by conformational
      sampling for larger proteins, that is, leaving a local energy minimum in which
      the search algorithm may get stuck. Here, we test the hypothesis that iteration
      of Rosetta with an orthogonal sampling and scoring strategy might facilitate
      exploration of conformational space. Specifically, we run short molecular
      dynamics (MD) simulations on models created by de novo folding of large proteins
      into cryoEM density maps to enable sampling of conformational space not directly
      accessible to Rosetta and thus provide an escape route from the conformational
      traps. We present a combined MD-Rosetta protein structure refinement protocol
      that can overcome some of these sampling limitations. Two of four benchmark
      proteins showed incremental improvement through all three rounds of the iterative
      refinement protocol. Molecular dynamics is most efficient in applying subtle but
      important rearrangements within secondary structure elements and is thus highly
      complementary to the Rosetta refinement, which focuses on side chains and loop
      regions.

PMID- 23956702
TI  - Drug Addiction Stigma in the Context of Methadone Maintenance Therapy: An
      Investigation into Understudied Sources of Stigma.
AB  - Experiences of stigma from others among people with a history of drug addiction
      are understudied in comparison to the strength of stigma associated with drug
      addiction. Work that has studied these experiences has primarily focused on
      stigma experienced from healthcare workers specifically even though stigma is
      often experienced from other sources as well. Because stigma has important
      implications for the mental health and recovery efforts of people in treatment,
      it is critical to better understand these experiences of stigma. Therefore, we
      characterize drug addiction stigma from multiple sources using qualitative
      methodology to advance understandings of how drug addiction stigma is experienced
      among methadone maintenance therapy patients and from whom. Results demonstrate
      that methadone maintenance therapy patients experience prejudice, stereotypes,
      and discrimination from friends and family, coworkers and employers, healthcare
      workers, and others. Discussion highlights similarities and differences in stigma
      experienced from these sources.

PMID- 23956703
TI  - On Plasmon Polariton Propagation Along Metallic Nano-Chain.
AB  - The collective wave type plasmon polariton self-modes in the metallic (Au, Ag)
      nano-chain were determined and analyzed with respect to the nano-sphere size and
      chain separation parameters. At some regions for parameters, the undamped modes
      were identified when the interaction had been assumed as the near-field-zone
      dipole coupling. These modes were found on the rim of stability of the linear
      theory, which indicates artifact of the model of near-field coupling. Inclusion
      of the medium- and far-field zone contributions to dipole interaction removes,
      however, instability and allows for fully analytical demonstration of quenching
      of irradiation losses of plasmon polaritons in the chain to the level of only
      ohmic attenuation. The plasmon polariton dispersion and the group velocity of
      plasmon polariton wave packets were examined with respect to nano-sphere and
      chain parameters and mode polarization. Previous numerical results related to
      long-range plasmon polariton propagation in the chain are transparently
      interpreted within the analytical approach.

PMID- 23956704
TI  - Theoretical Study of the Local Surface Plasmon Resonance Properties of Silver
      Nanosphere Clusters.
AB  - The local surface plasmon resonance properties in systems consisting of silver
      nanosphere clusters are studied by Green's function. The extinction, absorption,
      and scattering efficiencies band of two, three, and more silver nanospheres
      clusters are discussed in detail. The clusters show new types of the local
      surface plasmon resonances compared with single silver nanosphere. Our results
      suggest that the resonances depend strongly on individual particles'
      characteristics such as their shapes, gap distances, directions and polarizations
      of incident light waves, and the number of clusters. The spectrum shows that
      equilateral triangle nanospheres has a good absorption peak, while the better red
      shifted with three aligned nanospheres. In addition, the distributions of
      electric field intensity for three and four touched silver nanospheres are also
      investigated. The study is useful to broaden the application scope of Raman
      spectroscopy and nanooptics.

PMID- 23956705
TI  - Nonparametric Bayesian models for a spatial covariance.
AB  - A crucial step in the analysis of spatial data is to estimate the spatial
      correlation function that determines the relationship between a spatial process
      at two locations. The standard approach to selecting the appropriate correlation
      function is to use prior knowledge or exploratory analysis, such as a variogram
      analysis, to select the correct parametric correlation function. Rather that
      selecting a particular parametric correlation function, we treat the covariance
      function as an unknown function to be estimated from the data. We propose a
      flexible prior for the correlation function to provide robustness to the choice
      of correlation function. We specify the prior for the correlation function using
      spectral methods and the Dirichlet process prior, which is a common prior for an
      unknown distribution function. Our model does not require Gaussian data or
      spatial locations on a regular grid. The approach is demonstrated using a
      simulation study as well as an analysis of California air pollution data.

PMID- 23956706
TI  - Neuromuscular transmission monitoring: Beyond the electric shocks and the shaking
      hands.

PMID- 23956707
TI  - Analgesic efficacy of peritubal infiltration of ropivacaine versus ropivacaine
      and morphine in percutaneous nephrolithotomy under ultrasonic guidance.
AB  - BACKGROUND AND PURPOSE: Percutaneous nephrolithotomy is a safe and effective
      endourologic procedure which is less morbid than open surgery. However, pain
      around a nephrostomy tube requires good post-operative analgesia. We hypothesize
      that infiltration of local anesthetic with opioid from the renal capsule to the
      skin around the nephrostomy tract under ultrasonic guidance would alleviate the
      postoperative pain for a long period. METHODS: A total of 60 ASA physical status
      I to II patients were selected for a prospective randomized double-blind
      controlled study in percutaneous nephrolithotomy surgeries. Patients were divided
      into group R (n=30) and group RM (n=30). Balanced general anesthesia was given.
      After completion of the surgical procedure, a 23-gauze spinal needle was inserted
      at 6 and 12 O'clock position under ultrasonic guidance up to renal capsule along
      the nephrostomy tube. A 10 ml drug solution was infiltrated in each tract while
      withdrawing from renal capsule to the skin. After extubation, the patient was
      shifted to the post-anesthesia care unit for 24 hours. Post-operative pain was
      assessed using the visual analog scale (VAS) and dynamic visual analog scale
      (DVAS) (during deep breathing and coughing) rating 0-10 for initial 24 hours.
      Rescue analgesia was given in the form of injection tramadol 1.0 mg/kg
      intravenously when VAS >=4 and maximum up to 400 mg in 24 hours. Time to 1(st)
      rescue analgesic, number of doses of tramadol and total consumption of tramadol
      required in initial 24 hours were noted. Patients were observed for any side
      effect and treated accordingly. RESULTS: Time to 1(st) rescue analgesic, i.e.,
      duration of analgesia in group RM is more prolonged than group R (P=0.0004). The
      number of doses of tramadol in 24 hours in group R were higher as compared to
      group RM (P=0.0003). The total amount of tramadol in 24 hours in group R was more
      than in group RM (P=0.0013). Side effects like nausea and vomiting and sedation
      were comparable in both the groups. CONCLUSION: Addition of morphine to
      ropivacaine for nephrostomy tract infiltration significantly prolonged the
      duration of post-operative analgesia and reduced the number of doses and total
      consumption of rescue analgesic in initial 24 hours in percutaneous
      nephrolithotomy surgery.

PMID- 23956708
TI  - Assessment of current undergraduate anesthesia course in a Saudi University.
AB  - BACKGROUND: The assessment of the anesthesia course in our university comprises
      Objective Structured Clinical Examinations (OSCEs), in conjunction with portfolio
      and multiple-choice questions (MCQ). The objective of this study was to evaluate
      the outcome of different forms of anesthesia course assessment among 5(th) year
      medical students in our university, as well as study the influence of gender on
      student performance in anesthesia. METHODS: We examined the performance of 154,
      5(th) year medical students through OSCE, portfolios, and MCQ. RESULTS: The score
      ranges in the portfolio, OSCE, and MCQs were 16-24, 4.2-28.9, and 15.5-44.5,
      respectively. There was highly significant difference in scores in relation to
      gender in all assessments other than the written one (P=0.000 for Portfolio,
      OSCE, and Total exam, whereas P=0.164 for written exam). In the generated linear
      regression model, OSCE alone could predict 86.4% of the total mark if used alone.
      In addition, if the score of the written examination is added, OSCE will drop to
      57.2% and the written exam will be 56.8% of the total mark. CONCLUSIONS: This
      study demonstrates that different clinical methods used to assess medical
      students during their anesthesia course were consistent and integrated. The
      performance of female was superior to male in OSCE and portfolio. This
      information is the basis for improving educational and assessment standards in
      anesthesiology and for introducing a platform for developing modern learning
      media in countries with dearth of anesthesia personnel.

PMID- 23956709
TI  - Dose sparing of induction dose of propofol by fentanyl and butorphanol: A
      comparison based on entropy analysis.
AB  - BACKGROUND: The induction dose of propofol is reduced with concomitant use of
      opioids as a result of a possible synergistic action. AIM AND OBJECTIVES: The
      present study compared the effect of fentanyl and two doses of butorphanol pre
      treatment on the induction dose of propofol, with specific emphasis on entropy.
      METHODS: Three groups of 40 patients each, of the American Society of
      Anaesthesiologistsphysical status I and II, were randomized to receive fentanyl 2
      MUg/kg (Group F), butorphanol 20 MUg/kg (Group B 20) or 40 MUg/kg (Group B 40) as
      pre-treatment. Five minutes later, the degree of sedation was assessed by the
      observer's assessment of alertness scale (OAA/S). Induction of anesthesia was
      done with propofol (30 mg/10 s) till the loss of response to verbal commands.
      Thereafter, rocuronium 1 mg/kg was administered and endotracheal intubation was
      performed 2 min later. OAA/S, propofol induction dose, heart rate, blood
      pressure, oxygen saturation and entropy (response and state) were compared in the
      three groups. STATISTICAL ANALYSIS: Data was analyzed using ANOVA test with
      posthoc significance, Kruskal-Wallis test, Chi-square test and Fischer exact
      test. A P<0.05 was considered as significant. RESULTS: The induction dose of
      propofol (mg/kg) was observed to be 1.1+/-0.50 in Group F, 1.05+/-0.35 in Group B
      20 and 1.18+/-0.41 in Group B40. Induction with propofol occurred at higher
      entropy values on pre-treatment with both fentanyl as well as butorphanol.
      Hemodynamic variables were comparable in all the three groups. CONCLUSION:
      Butorphanol 20 MUg/kg and 40 MUg/kg reduce the induction requirement of propofol,
      comparable to that of fentanyl 2 MUg/kg, and confer hemodynamic stability at
      induction and intubation.

PMID- 23956710
TI  - Infraclavicular brachial plexus block: Comparison of posterior cord stimulation
      with lateral or medial cord stimulation, a prospective double blinded study.
AB  - BACKGROUND: Infraclavicular approach to the brachial plexus sheath provides
      anesthesia for surgery on the distal arm, elbow, forearm, wrist, and hand. It has
      been found that evoked distal motor response or radial nerve-type motor response
      has influenced the success rate of single-injection infraclavicular brachial
      plexus block. AIM: We conducted this study to compare the extent and
      effectiveness of infraclavicular brachial plexus block achieved by injecting a
      local anesthetic drug after finding specific muscle action due to neural
      stimulator guided posterior cord stimulation and lateral cord/medial cord
      stimulation. METHODS: After ethical committee approval, patients were randomly
      assigned to one of the two study groups of 30 patients each. In group 1,
      posterior cord stimulation was used and in group 2 lateral/medial cord
      stimulation was used for infraclavicular brachial plexus block. The extent of
      motor block and effectiveness of sensory block were assessed. RESULTS: All four
      motor nerves that were selected for the extent of block were blocked in 23 cases
      (76.7%) in group 1 and in 15 cases (50.0%) in group 2 (P:0.032). The two groups
      did not differ significantly in the number of cases in which 0, 1, 2, and 3
      nerves were blocked (P>0.05). In group 1, significantly lesser number of patients
      had pain on surgical manipulation compared with patients of group 2 (P:0.037).
      CONCLUSION: Stimulating the posterior cord guided by a nerve stimulator before
      local anesthetic injection is associated with greater extent of block (in the
      number of motor nerves blocked) and effectiveness of block (in reporting no pain
      during the surgery) than stimulation of either the lateral or medial cord.

PMID- 23956711
TI  - Does dexamethasone prevent subarachnoid meperidin-induced nausea, vomiting and
      pruritus after cesarean delivery?
AB  - BACKGROUND: Opioid-induced side effects such as nausea and vomiting and pruritus
      are common and may be more debilitating than pain itself. We performed a study to
      assess the efficacy of dexamethasone in reducing postoperative nausea, vomiting,
      and pruritus in patients receiving neuraxial anesthesia with meperidine. METHODS:
      Fifty-two women undergoing cesarean section were enrolled in the study. The
      control group and dexamethasone group received intravenously normal saline and
      dexamethasone, respectively, before spinal anesthesia. The occurrence of
      postoperative nausea, vomiting, and pruritus was assessed for 24 h in both
      groups. RESULTS: The overall incidence of nausea and vomiting during the 24 h
      follow-up period was 37% and 22.2% for group saline and 20% and 12% for group
      dexamethasone, respectively (P=0.175, 0.469). The incidence of pruritus was not
      significantly different between the two groups. Pruritus severity was
      significantly less in the dexamethasone group than in the saline group (P=0.019).
      CONCLUSION: Prophylactic dexamethasone does not reduce the incidence of
      subarachnoid meperidine-induced nausea, vomiting, and pruritus in women
      undergoing cesarean delivery.

PMID- 23956712
TI  - Hemiarthroplasty in high risk elderly patient under epidural anesthesia with
      0.75% ropivacaine-fentanyl versus 0.5% bupivacaine-fentanyl: Clinical trial.
AB  - BACKGROUND: Anesthetic management of elderly patients is a challenge as aging
      makes them more susceptible to hemodynamic fluctuations during regional
      anesthesia. This study was aimed to compare the clinical efficacy of epidural
      0.75% ropivacaine fentanyl (RF)- with 0.5% bupivacaine-fentanyl (BF) for
      hemiarthroplasty in high-risk elderly patients. METHODS: Sixty elderly consented
      patients of either sex with American Society of Anesthesiologist ASA II and III,
      scheduled for elective hemiarthroplasty were randomized into two Groups of 30
      patients to receive epidural study solution of 15 mL of 0.75% Ropivacaine or 0.5%
      Bupivacaine with 1 mL fentanyl (50 MUg). The hemodynamic variability with onset
      and duration of sensory and motor blocks were recorded. The adequacy and quality
      of surgical anesthesia were assessed. The post-epidural nausea and vomiting,
      shivering, respiratory parameters, or any other side effects were also recorded.
      RESULTS: There was no difference in the demographic profile between groups. The
      mean onset time to achieve sensory block to the T10 dermatome was rapid in the
      Group BF (12.4+/-6.9 vs. 17.5+/-3.7 min in Group RF). The mean time to achieve
      motor block was 17.5+/-3.4 min in Group BF versus 21.7+/-7.8 min in Group RF. The
      intraoperative hemodynamic fluctuations showed statistically significant
      differences between groups. The pruritis was observed in five patients but post
      epidural shivering, nausea, vomiting, respiratory depression, or urinary
      retention were not observed in any patient. CONCLUSION: Epidural 0.75%
      Ropivacaine with fentanyl showed better clinical profile as compared to 0.5%
      Bupivacaine with fentanyl for hemiarthroplasty in elderly patients.

PMID- 23956713
TI  - A survey of the current use of neuromuscular blocking drugs among the Middle
      Eastern anesthesiologists.
AB  - BACKGROUND: This survey aimed to assess the extent of practice of the Middle
      Eastern anesthesiologists in the use of neuromuscular blocking agents (NMB) in
      2012. METHODS: We distributed an electronic survey among 577 members of the
      Triple-M Middle Eastern Yahoo anesthesia group, enquiring about their practice in
      the use of neuromuscular blocking agents. Questions concerned the routine first
      choice use of NMB, choice for tracheal intubation, the use of neuromuscular
      monitoring (NMT), type of NMB used in difficult airway, frequency of using
      suxamethonium, cisatracurium, rocuronium and sugammadex, observed side effects of
      rocuronium, residual curarization, and the reversal of residual curarization of
      rocuronium. RESULTS: A total of 71 responses from 22 Middle Eastern institutions
      were collected. Most of the Middle Eastern anesthesiologists were using
      cisatracurium and rocuronium frequently for tracheal intubation (39% and 35%,
      respectively). From the respondents, 2/3 were using suxamethonium for tracheal
      intubation in difficult airway, 1/3 were using rocuronium routinely and 17% have
      observed hypersensitivity reactions to rocuronium, 54% reported residual
      curarization from rocuronium, 78% were routinely using neostigmine to reverse the
      rocuronium, 21% used sugammadex occasionally, and 35% were using NMT routinely
      during the use of NMB. CONCLUSIONS: We believe that more could be done to
      increase the awareness of the Middle Eastern anesthesiologists about the high
      incidence of PROC (>20%) and the need for routine monitoring of neuromuscular
      function. This could be accomplished with by developing formal training programs
      and providing official guidelines.

PMID- 23956714
TI  - N-acetylcysteine instead of theophylline in patients with COPD who are candidates
      for elective off-pump CABG surgery: Is it possible in cardiovascular surgery
      unit?
AB  - BACKGROUND: Forced expiratory volume in one second (FEV1) is a good predictor of
      chronic obstructive pulmonary disease (COPD). COPD is characterized by a chronic
      limitation of airflow. This study was designed to compare the effects and
      complications of theophylline alone, N-acetylcysteine (NAC) alone, and a
      combination of the two drugs on the rates of FEV1 in patients with COPD who were
      candidates for off-pump coronary artery bypass graft (CABG) surgery. METHODS:
      This clinical trial was performed on 100 patients who had a smoking history of 27
      pack years with a range of 20 to 40 pack years but were not heavy smokers and
      were candidates for elective off-pump CABG surgery in Afshar Cardiovascular
      Hospital, Yazd, Iran. The patients with a history of asthma and bronchospasm and
      non-COPD respiratory disorders were excluded. There were three groups, that is,
      the theophylline group (n=33) that received theophylline 10 mg/kg TDS after
      consumption of food, NAC group (n=33) who received NAC 10-15 mg/kg BD after
      consumption of food, and the combined group (n=32) who received theophylline and
      NAC together. Data were analyzed by analysis of variance (ANOVA), Chi-square, and
      exact test for quantitative and qualitative variables. RESULTS: One hundred
      patients with COPD enrolled in this study as possible candidates for CABG
      surgery. Average age of the patients was 60.36+/-10.21 years. Of the
      participants, 83 (83.3%) were male and 17 (17%) were female. Rate of
      postoperative FEV1 to basal FEV1 was 0.76+/-0.32, 0.66+/-0.22, and 0.69+/-0.24 in
      the treatments with theophylline, NAC, and the combination, respectively.
      Theophylline, NAC, and a combination of these drugs can decrease the rate of
      postoperative FEV1 compared to basal FEV1 significantly. (P=0.0001). CONCLUSION:
      Theophylline alone, NAC alone, and a combination of these drugs improve pulmonary
      function, and there are no significant differences between these protocols.
      Stomach discomfort and cardiac complications in treatment with theophylline alone
      is significantly higher than NAC alone and the combination.

PMID- 23956715
TI  - Prevalence of obstructive sleep apnea in surgical patients presenting to a
      tertiary care teaching hospital in India: A preliminary study.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is often not diagnosed in patients
      presenting for surgical procedures thereby increasing the incidence of adverse
      perioperative course. Early diagnosis of this disease is important in modifying
      anesthetic management as well as utilizing specific means which may decrease the
      complications and improve the patient outcome. METHODS: Patients greater than
      eighteen years of age, ASA I-III scheduled for elective surgical procedures under
      anesthesia were randomly selected. Their demographic data, diagnosis and nature
      of surgery were noted in a semi-structured performa. They were then screened for
      the presence of OSA with the help of a STOP BANG questionnaire. RESULTS: This
      study included two hundred four patients randomly selected. Slight female
      predominance was seen in this sample (55.4%). Mean age of the subjects was 42.7
      years (SD=15.08). 24.5% subjects were at high risk for OSA (STOP-BANG>3) with a
      male predominance (72% versus 37% in low risk group; X (2)=18.62; P<0.001). High
      risk OSA subjects had higher prevalence of cardiovascular risk factors (57% vs.
      11.7% in low risk group; X (2)=33.35; P<0.001). Similarly, this group had a
      higher prevalence of asthma and chronic obstructive pulmonary disease (COPD) (14%
      versus 3.8% in low risk group; X (2)=6.54; P=0.03). Prevalence of diabetes
      mellitus (22%) and hypothyroidism (6%) was also higher in this group (5.2% and
      1.9% in low risk group respectively; X (2)=15.42; P<0.001). CONCLUSION: High
      degree of suspicion and knowledge of association of OSA and medical diseases may
      help in detection of such cases and decrease the rate of perioperative
      complications thus improving patients safety.

PMID- 23956716
TI  - Comparison of the effects of remifentanil and alfentanil on intraocular pressure
      in cataract surgery.
AB  - BACKGROUND: Anesthesia for ophthalmic surgery requires management of intraocular
      pressure (IOP) during perioperative period. In an open eye, in conditions such as
      after traumatic injury or during cataract surgery, IOP increase can lead to
      permanent vision loss. Administration of narcotics concomitant with anesthetics
      has the ability to reduce this increase of IOP. This clinical trial aims to
      compare the efficacy of remifentanil and alfentanil in preventing an increase in
      IOP after administration of succinylcholine, intubation and during anesthesia.
      METHODS: This double-blind clinical trial was conducted on 50 patients undergoing
      elective general surgery for cataracts. Patients were randomly divided into two
      groups. Alfentanil (20 MUg/kg in 30 s) for group 1 and remifentanil (1 MUg/kg in
      30 s) for group 2 were injected before induction of anesthesia, and 0.5
      MUg/kg/min alfentanil for group 1 and 0.1 MUg/kg/min remifentanil for group 2
      were infused during the anesthesia. Systolic and diastolic blood pressure, heart
      rate, and IOP from normal eye were measured before the induction, after
      administration of thiopental and succinylcholine, after tracheal intubation, and
      2 min later, and were repeated in 2-min intervals until the end of operation.
      RESULTS: IOP decreased after injection of anesthetics and remained lower all
      through the operation in both groups, but IOP decreased after injection of
      succinylcholine in remifentanil group while it increased in alfentanil group
      (P<0.05). CONCLUSIONS: Results of this study indicate benefits of both
      remifentanil and alfentanil in managing IOP after induction and during
      anesthesia. It seems that remifentanil is better than alfentanil in controlling
      the IOP after injection of succinylcholine.

PMID- 23956717
TI  - LMA C Trach aided endotracheal intubation in simulated cases of cervical spine
      injury: A series of 30 cases.
AB  - BACKGROUND: Laryngeal mask airway (LMA) C Trach is a novel device designed to
      intubate trachea without conventional laryngoscopy. The aim of the study was to
      evaluate the clinical efficacy of C trach in the simulated scenario of cervical
      spine injury where conventional laryngoscopy is not desirable. METHODS: This
      prospective pilot study was carried out in 30 consenting adults of either gender,
      ASAPS I or II, scheduled for surgery requiring endotracheal intubation. An
      appropriate sized rigid cervical collar was positioned around the patient's neck
      to restrict the neck movements and simulate the scenario of cervical spine
      injury. After induction of anesthesia, various technical aspects of C Trach
      facilitated endotracheal intubation, changes in hemodynamic variables, and
      complications were recorded. RESULTS: Mask ventilation was easy in all the
      patients. Successful insertion of C Trach was achieved in 27 patients at first
      attempt, while 3 patients required second attempt. Majority of patients required
      one of the adjusting maneuvers to obtain acceptable view of glottis (POGO score
      >50%). Intubation success rate was 100% with 26 patients intubated at first
      attempt and the rest required second attempt. Mean intubation time was 69.8+/
      27.40 sec. With experience, significant decrease in mean intubation time was
      observed in last 10 patients as compared to first 10 (46+/-15.77 sec vs. 101.3+/
      22.91 sec). Minor mucosal injury was noted in four patients. CONCLUSION: LMA C
      Trach facilitates endotracheal intubation under direct vision and can be a useful
      technique in patients with cervical spine injury with cervical collar in situ.

PMID- 23956718
TI  - Patients', who applied to the anesthesia clinic, perceptions and knowledge about
      anesthesia in Turkiye.
AB  - BACKGROUND: Pre-operative evaluation includes determining the patient's
      physiological and psychological situation, taking information about
      pharmacological and therapeutic history, laboratory examinations, and identifying
      the anesthesia risks. The aim of this study is to learn the patients', who
      planned for elective surgery, knowledge and perception about anesthesia, to
      determine the causes of fears, to investigate whether age, gender, education
      level, and history of operation affect the outcome of the survey. METHODS: A
      questionnaire consisting of 21 questions was asked to fill by the patients who
      applied to the anesthesia clinic. In our study, totally 250 patients, aged
      between 16 and 75 were included. The questionnaire consists of two parts: The
      first part includes demographic data such as age, gender, education level,
      occupation; the second part includes the questions about anesthesia experience
      and knowledge. RESULTS: Of the 250 patients studied, 59% were females and 41%
      were males. Of these patients, 37.6% had secondary education. As occupation, the
      highest percentage was belonging to the housewives (33.6%). In the second part of
      the questionnaire, it was showed that having an anesthesia experience and high
      education status statistically significantly affect the level of information
      about anesthesia (P=0.001; P=0.001). CONCLUSION: In this study, it was showed
      that there is an important relationship between education and past anesthesia
      experience and having information about anesthesia and anesthetists. But,
      generally it was also showed that the patients not having adequate information
      about anesthesia and anesthetists and to provide the public more informed about
      anesthesia, with hospital policies and studies of increasing education level, the
      individual attempts of anesthetists and continuous studies for anesthesia
      displaying are needed.

PMID- 23956719
TI  - Induced hypotension for functional endoscopic sinus surgery: A comparative study
      of dexmedetomidine versus esmolol.
AB  - OBJECTIVE: A comparative study to evaluate the efficacy of dexmedetomidine as a
      hypotensive agent in comparison to esmolol in Functional Endoscopic Sinus Surgery
      (FESS). METHODS: Forty patients ASA I or II scheduled for FESS were equally
      randomly assigned to receive either dexmedetomidine 1 MUg/Kg over 10 min before
      induction of anesthesia followed by 0.4-0.8 MUg/Kg/h infusion during maintenance
      (DEX group), or esmolol, loading dose 1mg/kg was infused over one min followed by
      0.4-0.8 mg/kg/h infusion during maintenance (E group) to maintain mean arterial
      blood pressure (MAP) between (55-65 mmHg). General anesthesia was maintained with
      sevoflurane 2%-4%. The surgical field was assessed using Average Category Scale
      and average blood loss was calculated. Hemodynamic variables (MAP and HR);
      arterial blood gas analysis; plasma cortisol level; intraoperative fentanyl
      consumption; Emergence time and total recovery from anesthesia (Aldrete score
      >=9) were recorded. Sedation score was determined at 15, 30, 60 min after
      tracheal extubation and time to first analgesic request was recorded. RESULT:
      Both DEX group and E group reached the desired MAP (55-65 mmHg) with no
      intergroup differences in MAP or HR. The for the quality of the surgical filed in
      the range of MAP (55-65 mmHg) were <=2 with no significant differences between
      group scores during hypotensive period. Mean intraoperative fentanyl consumption
      was significantly lower in DEX group than E group. Cortisol level showed no
      significant changes between or within groups. No significant changes were
      observed in arterial blood gases. Emergence time and time to achieve Aldrete
      score >=9 were significantly lower in E group compared with DEX group. The
      sedation score were significantly lower in E group compared with DEX group at 15
      and 30 minutes postoperatively. Time to first analgesic request was significantly
      longer in DEX group. CONCLUSION: Both dexmedetomidine or esmolol with sevoflurane
      are safe agents for controlled hypotension and are effective in providing ideal
      surgical field during FESS. Compared with esmolol, dexmedetomidine offers the
      advantage of inherent analgesic, sedative and anesthetic sparing effect.

PMID- 23956720
TI  - The comparative evaluation of intravenous with intramuscular clonidine for
      suppression of hemodynamic changes in laparoscopic cholecystectomy.
AB  - BACKGROUND: Clonidine diminishes stress response by reducing circulating
      catecholamines and hence increases perioperative circulatory stability in
      patients undergoing laparoscopic surgeries. The aim of this study was to compare
      intravenous (IV) clonidine (2 MUg/kg) with intramuscular (IM) clonidine (2
      MUg/kg) for attenuation of stress response in laproscopic surgeries. METHODS:
      Eighty adult patients classified as ASA physical status I or II, aged between 20
      and 60 years undergoing elective cholecystectomy under general anesthesia were
      enrolled for a prospective, randomized, and double-blind controlled trial. They
      received either IV clonidine (2 MUg/kg) 15 min prior to the scheduled surgery
      (Group I) or IM clonidine (2 MUg/kg) 60-90 min prior to the scheduled surgery
      (Group II). Hemodynamic variables (Heart rate, systolic (SBP), diastolic (DBP),
      mean arterial pressure (MAP)), SpO2 and EtCO2 were recorded at specific times -
      baseline, prior to induction, 1 min after intubation, before CO2, insufflation,
      after CO2 insufflation at 1,5,10,20,30,45,60 min, after release of CO2, at 1 and
      10 minutes after extubation. Secondary outcomes included evaluation of adverse
      effect profile of the two groups. RESULTS: No significant difference was observed
      in the HR throughout the intraoperative period in between the two groups
      (P>0.05). There was statistically significant difference in SBP between the two
      groups starting from 1 minute after induction till 1 min after extubation
      (P<0.05) but not in DBP except at 1 minute after intubation (P=0.042).
      Significant difference in MAP was noted at 1 minute after intubation (P=0.004)
      and then from 5 minutes after CO2 insufflation to 1 minute after extubation
      (P<0.05). Incidence of adverse effects were higher in group II (P=0.02)
      especially incidence of hypertension requiring treatment (0.006). CONCLUSION: We
      conclude that under the conditions of this study, hemodynamic parameters (SBP,
      DBP and MAP) were better maintained in the IV as compared to the IM route that
      had significantly higher incidence of hypertension requiring treatment.

PMID- 23956721
TI  - Early brain injury and subarachnoid hemorrhage: Where are we at present?
AB  - The current era has adopted many new innovations in nearly every aspect of
      management of subarachnoid hemorrhage (SAH); however, the neurological outcome
      has still not changed significantly. These major therapeutic advances mainly
      addressed the two most important sequels of the SAH-vasospasm and re-bleed. Thus,
      there is a possibility of some different pathophysiological mechanism that would
      be responsible for causing poor outcome in these patients. In this article, we
      have tried to compile the current role of this different yet potentially
      treatable pathophysiological mechanism in post-SAH patients. The main
      pathophysiological mechanism for the development of early brain injury (EBI) is
      the apoptotic pathways. The macro-mechanism includes increased intracranial
      pressure, disruption of the blood-brain barrier, and finally global ischemia.
      Most of the treatment strategies are still in the experimental phase. Although
      the role of EBI following SAH is now well established, the treatment modalities
      for human patients are yet to be testified. 

PMID- 23956722
TI  - Successful retrieval of a knotted pulmonary artery catheter trapped in the
      tricuspid valve apparatus.
AB  - We report the case of a 64-year-old patient in whom a pulmonary artery catheter
      formed a knot fixed within the right ventricle in the region of the tricuspid
      valve apparatus. Knot formation is a recognized complication associated with
      pulmonary artery catheters (PAC) insertion. This problem is usually dealt with by
      simply withdrawing the PAC until the knot impacts onto the introducer and after
      enlarging the puncture site by a small skin incision removing the introducer-PAC
      as one unit. However, we recently encountered a situation where the PAC was
      knotted around the tricuspid valve apparatus and could not be withdrawn. An
      interventional radiologist was able to unknot the catheter and release it from
      the tricuspid valve. We reviewed the literature related to this topic. We believe
      our experience could be of use to others. 

PMID- 23956723
TI  - Esophageal misplacement of a single-lumen tube after its exchange for a double
      lumen tube despite the use of an airway-exchange catheter.
AB  - An airway-exchange catheter (AEC) can increase the safety of exchanges of
      endotracheal tubes (ETTs); however, the procedure is associated with potential
      risks. We describe a case of esophageal misplacement of a single-lumen ETT after
      switching from a double-lumen tube, despite the use of an AEC as a guidewire. To
      avoid this, physicians should consider the insertion depth and maintenance depth
      of the AEC and should verify its position before changing ETTs and should
      perform, if possible, with simultaneous visualization of the glottis with direct
      or video laryngoscopy during the exchange. Additionally, the new ETT position
      should be confirmed by auscultation, end-tidal carbon dioxide, and portable chest
      X-ray. 

PMID- 23956724
TI  - Child with bilateral pheochromocytoma and a surgically solitary kidney:
      Anesthetic challenges.
AB  - Pheochromocytoma is a rare neuroendocrine tumor of childhood. We present a 14
      year-old boy with bilateral pheochromocytoma, post nephrectomy in view of a non
      functioning kidney presenting with severe hypertension and end organ damage.
      Diagnosis was confirmed with 24-hour urinary VMA, catechol amines, and CT scan.
      Preoperative blood pressure (BP) was controlled with prazosin, propranolol,
      nicardipine, and HCT-spironolactone. Anesthesia was given with general
      endotracheal anesthesia with epidural analgesia. Intraoperative BP rise was
      managed with infusion of NTG, MgSO4, esmolol, and dexmedetomidine which was
      especially challenging on account of bilateral tumor. 

PMID- 23956725
TI  - Anesthetic management of a child with corrected transposition of great vessels
      undergoing non-cardiac surgery.
AB  - We describe the successful anesthetic management of a 14-year-old child, a
      corrected case of transposition of great vessels in childhood and presently with
      residual atrial septal defect, peripheral cyanosis, and neurological deficit of
      lower limb presented for tendoachillis lengthening. 

PMID- 23956726
TI  - Pourfour Du Petit syndrome after interscalene block.
AB  - Interscalene block is commonly associated with reversible ipsilateral phrenic
      nerve block, recurrent laryngeal nerve block, and cervical sympathetic plexus
      block, presenting as Horner's syndrome. We report a very rare Pourfour Du Petit
      syndrome which has a clinical presentation opposite to that of Horner's syndrome
      in a 24-year-old male who was given interscalene block for open reduction and
      internal fixation of fracture upper third shaft of left humerus. 

PMID- 23956727
TI  - Posterior leukoencephalopathy syndrome: Postpartum focal neurologic deficits: A
      report of three cases and review of the literature.
AB  - Posterior reversible encephalopathy syndrome presents with a variety of
      neurologic features, which, although devastating at some point, are potentially
      reversible on prompt recognition and institution of appropriated treatment. We
      report the management of three cases occurring in the last 4 years in our
      tertiary university hospital. 

PMID- 23956728
TI  - Anaesthetic challenges in a patient presenting with huge neck teratoma.
AB  - Paediatric airway management is a great challenge even for an experienced
      anaesthesiologist. Difficult airway in huge cervical teratoma further exaggerates
      the complexity. This case report is intended at describing the intubation
      difficulties that were confronted during the airway management of a three year
      old girl presenting with huge neck teratoma and respiratory distress. This
      patient was successfully intubated with uncuffed endotracheal tubes in second
      attempt under inhalational anaesthesia with halothane and spontaneous
      ventilation. This case exemplifies the importance of careful preoperative workup
      of an anticipated difficult airway in paediatric patients with neck swelling to
      minimize any perioperative complications. 

PMID- 23956729
TI  - Be prepared for the unexpected!

PMID- 23956730
TI  - Dry spinal tap due to primary psoas and paraspinal abscesses.

PMID- 23956731
TI  - Recurrent bradycardia and asystole in a patient undergoing supratentorial tumor
      resection: Different types of trigeminal cardiac reflex in same patients.

PMID- 23956732
TI  - Unusual bifid "V" wave in central venous pressure.

PMID- 23956733
TI  - Mephentermine triggered anaphylaxis in the peri-operative period: An unusual
      occurrence.

PMID- 23956734
TI  - A case of extensive cardiac calcification.

PMID- 23956735
TI  - A case of "anesthesia mumps" from ICU.

PMID- 23956736
TI  - Plagiarism, management, journal retraction and response by author's institute.

PMID- 23956737
TI  - Color image quantization algorithm based on self-adaptive differential evolution.
AB  - Differential evolution algorithm (DE) is one of the novel stochastic optimization
      methods. It has a better performance in the problem of the color image
      quantization, but it is difficult to set the parameters of DE for users. This
      paper proposes a color image quantization algorithm based on self-adaptive DE. In
      the proposed algorithm, a self-adaptive mechanic is used to automatically adjust
      the parameters of DE during the evolution, and a mixed mechanic of DE and K-means
      is applied to strengthen the local search. The numerical experimental results, on
      a set of commonly used test images, show that the proposed algorithm is a
      practicable quantization method and is more competitive than K-means and particle
      swarm algorithm (PSO) for the color image quantization. 

PMID- 23956738
TI  - Prevention and management of complications of and training for colorectal
      endoscopic submucosal dissection.
AB  - Endoscopic submucosal dissection (ESD) is reported to be an efficient treatment
      with a high rate of en bloc resection for large colorectal tumors in Japan and
      some other Western and Asian countries. ESD is considered less invasive than
      laparoscopic colectomy. However, ESD carries a higher risk of perforation than
      endoscopic mucosal resection (EMR). Various devices and training methods for
      colorectal ESD have been developed to solve the difficulties. In this review, we
      describe the complications of colorectal ESD and prevention of those
      complications. On the other hand, colorectal ESD is difficult for less
      experienced endoscopists. The unique step-by-step ESD training system is
      performed in Japan. Additionally, appropriate training, including animal model
      training, for colorectal ESD should be acquired before working on clinical cases.

PMID- 23956739
TI  - The Clinical Correlations of Helicobacter pylori Virulence Factors and Chronic
      Spontaneous Urticaria.
AB  - Background and Study Aims. The association between Helicobacter pylori (H.
      pylori) and chronic spontaneous urticaria (CSU) remains controversial. This study
      explored the role of H. pylori in CSU among different virulent genotypes
      patients. Patients and Methods. Patients infected by H. pylori were sorted into
      two groups as group A (with CSU) and group B (without CSU). The tissue materials
      were taken via endoscopy for polymerase chain reaction study to determine
      virulence factors. After H. pylori eradication therapy, the eradication rate and
      response of urticaria were evaluated by using C(13)-UBT and a three-point scale
      (complete remission, partial remission, or no improvement). Results. The results
      were comparable between patients of groups A and B in terms of H. pylori
      infection rates and eradication rate. Longitudinal follow-up of 23.5 months
      showed complete remission of urticaria in 63.6% but no improvement in 36.4% of
      the patients after H. pylori eradication. H. pylori infected patients with
      different virulence factors such as cytotoxin-associated gene A, vacuolating
      cytotoxin gene A signal region and middle region have similar remission rates for
      CSU. Conclusions. Current study suggests that H. pylori may play a role in the
      development and disease course of CSU but may be irrelevant to different virulent
      genotypes. 

PMID- 23956740
TI  - Penile fracture: experience from a third world country.
AB  - Aim. To ascertain the clinical presentation, commonest age group affected, and
      treatment of patients diagnosed to have penis fracture. Materials and Methods. We
      performed a retrospective study carried at a tertiary care hospital from January
      2005 to January 2011. All the 36 patients diagnosed to have penile fracture were
      enrolled in the study group. The diagnosis was made based on the clinical
      findings in the patients. All, except two patients, were managed by a standard
      surgical procedure, same for all the patients, on the day of presentation to the
      hospital. All the data pertaining to the presentation, management, and followup
      of these patients were studied and scrutinized thoroughly. Results. Thirty-four
      patients were operated while 2 refused surgery. Most of our patients were between
      16 and 30 years (55.6%) of age. The commonest presenting complaints were penile
      swelling and detumescence during sexual intercourse or an erection. All except
      two of our patients were managed with immediate surgical repair which had
      excellent results even in the presence of associated urethral injury. Conclusion.
      Fracture of the penis is a surgical emergency which can be best managed by
      immediate surgical repair with excellent results even in the presence of urethral
      injury. 

PMID- 23956741
TI  - Prevalence of Priapism and Its Awareness amongst Male Homozygous Sickle Cell
      Patients in Lagos, Nigeria.
AB  - Background. Priapism is a pathological condition of penile erection that persists
      beyond, or is unrelated to, sexual stimulation. Impotence and infertility are
      major problems in male sickle cell disease patients, and priapism has been
      implicated as a cause of impotence and infertility. The aim of this study is to
      determine priapism prevalence and assess the knowledge of male homozygous male
      patients about it in Lagos, Nigeria. Methods. A cross-sectional study was
      conducted amongst male homozygous sickle cell disease patients of Lagos State
      University Teaching Hospital. Pretested questionnaires were distributed to
      determine the prevalence and assess their knowledge on priapism. Data were
      analyzed using SPSS version 16.0. Results. A total of 114 consenting subjects
      filled the questionnaires, 85 of 114 (74.6%) had not heard about priapism before
      this study. A total of 77 of 114 (67.5%) did not know that they are at risk of
      priapism. Whilst 84 of 114 (73.7%) were not aware that priapism is a complication
      of SCD. The majority, 94 of 114 (82.5%), were not aware that priapism could cause
      impotence. Conclusion. There is a need to create more awareness about this
      complication amongst sickle cell disease patients in order to stem the incidence
      of impotence and infertility amongst them. 

PMID- 23956743
TI  - The Association of Sleep Disorder, Obesity Status, and Diabetes Mellitus among US
      Adults-The NHANES 2009-2010 Survey Results.
AB  - To examine the association between sleep disorders, obesity status, and the risk
      of diabetes in adults, a total of 3668 individuals aged 40+ years from the NHANES
      2009-2010 without missing information on sleep-related questions, measurements
      related to diabetes, and BMI were included in this analysis. Subjects were
      categorized into three sleep groups based on two sleep questions: (a) no sleep
      problems; (b) sleep disturbance; and (c) sleep disorder. Diabetes was defined as
      having one of a diagnosis from a physician; an overnight fasting glucose > 125
      mg/dL; Glycohemoglobin > 6.4%; or an oral glucose tolerance test > 199 mg/dL.
      Overall, 19% of subjects were diabetics, 37% were obese, and 32% had either sleep
      disturbance or sleep disorder. Using multiple logistic regression models
      adjusting for covariates without including BMI, the odds ratios (OR, (95% CI)) of
      diabetes were 1.40 (1.06, 1.84) and 2.04 (1.40, 2.95) for those with sleep
      disturbance and with sleep disorder, respectively. When further adjusting for
      BMI, the ORs were similar for those with sleep disturbance 1.36 (1.06, 1.73) but
      greatly attenuated for those with sleep disorders (1.38 [0.95, 2.00]). In
      conclusion, the impact of sleep disorders on diabetes may be explained through
      the individuals' obesity status. 

PMID- 23956744
TI  - Relationship between Adiponectin Level, Insulin Sensitivity, and Metabolic
      Syndrome in Type 1 Diabetic Patients.
AB  - Objective. Adiponectin is known to be decreased in insulin resistance (IR) and
      metabolic syndrome (MS) which can be present in patients with type 1 diabetes
      mellitus (T1DM). The aim of this study was to evaluate the relationship between
      adiponectin level, MS, and insulin sensitivity in T1DM. Research Design and
      Methods. The study included 77 T1DM patients divided into two groups based on the
      total plasma adiponectin median value. Insulin sensitivity was calculated with
      the equation for eGDR, and MS was defined according to International Diabetes
      Federation criteria. Results. Patients with higher adiponectin level (n = 39) had
      significantly lower waist circumference (P < 0.002), fasting venous glucose
      levels (P < 0.001), higher HDL3-cholesterol (P = 0.011), and eGDR (P = 0.003) in
      comparison to the group with lower adiponectin who showed higher prevalence of MS
      (P = 0.045). eGDR increased for 1.09 mg/kg(-1) min(-1) by each increase of 1  u
      g/mL total fasting plasma adiponectin (P = 0.003). In the logistic regression
      model, adiponectin was inversely associated with the presence of MS (P = 0.014).
      Conclusion. Higher adiponectin concentration is associated with lower prevalence
      of MS in T1DM. Whether higher adiponectin concentration has a protective role in
      the development of the MS in T1DM needs to be clarified in future follow-up
      studies. 

PMID- 23956742
TI  - Atherosclerosis Induced by Chlamydophila pneumoniae: A Controversial Theory.
AB  - More than a century ago, inflammation and infection were considered to have
      atherogenic effects. The old idea that coronary heart disease (CHD) possibly has
      an infectious etiology has only reemerged in recent years. Atherosclerosis is the
      main pathological process involved in CHD and is, logically, the first place to
      look for infectious etiology. The process of atherosclerosis itself provides the
      first hints of potential infectious cause. Smooth muscle proliferation, with
      subsequent intimal thickening, luminal narrowing, and endothelial degeneration,
      constitutes the natural history of atherosclerosis, being with the severity and
      speed of these changes. Both viral and bacterial pathogens have been proposed to
      be associated with the inflammatory changes found in atherosclerosis. Recently,
      Chlamydophila pneumoniae (C. pneumoniae) has been implicated as a possible
      etiologic agent of coronary artery disease and atherosclerosis. New evidence
      which supports a role for C. pneumoniae in the pathogenesis of atherosclerosis
      has emerged. C. pneumoniae has been detected in atherosclerotic arteries by
      several techniques, and the organism has been isolated from both coronary and
      carotid atheromas. Recent animal models have suggested that C. pneumoniae is
      capable of inducing atherosclerosis in both rabbit and mouse models of
      atherosclerosis. Furthermore, human clinical treatment studies which examined the
      use of antichlamydial macrolide antibiotics in patients with coronary
      atherosclerosis have been carried out. The causal relationship has not yet been
      proven, but ongoing large intervention trials and research on pathogenetic
      mechanisms may lead to the use of antimicrobial agents in the treatment of CHD in
      the future. 

PMID- 23956745
TI  - 25-hydroxyvitamin d and severity of Parkinson's disease.
AB  - Introduction. A role for vitamin D deficiency in Parkinson's disease (PD) has
      recently been proposed. Given the growing body of evidence for the association of
      vitamin D with several neurodegenerative disorders and unavailability of any
      published study in the Middle East, the present study is aimed to determine the
      associations of circulating 25-hydroxyvitamin D (25OHD) levels with the severity
      of PD in an Iranian sample. Methods. In 109 patients, the severity of PD was
      evaluated by using Hoehn & Yahr (HR) stages and Unified Parkinson's Disease
      Rating Stage (UPDRS) Part III compared with 25OHD level in a double-blind and
      cross-sectional study. Results. Mean +/- SD levels of 25OHD were 28.5 +/- 1.4 and
      27.1 +/- 1.5, for males and females, respectively. Also, 38.4% of the patients
      showed deficiency levels of 25OHD (<20 ng/mL), and 72.8% had insufficient levels
      (<30 ng/mL). High prevalence of 25OHD insufficiency in subjects with early
      disease was not associated with HR stage and UPDRS scores even after multivariate
      adjustment for possible confounders including disease duration. Conclusions.
      These findings are consistent with the possibility that vitamin D status does not
      seem to deteriorate during the early disease stages of PD. Further studies are
      needed to reveal the natural role and significance of vitamin D insufficiency in
      PD. 

PMID- 23956746
TI  - Gram-negative bacterial lipopolysaccharide stimulates activin a secretion from
      human amniotic epithelial cells.
AB  - Activin A is involved in inflammation. The present study was performed to clarify
      if lipopolysaccharide, a component of Gram-negative bacteria, stimulates activin
      A secretion from human amniotic epithelial cells and to determine if activin A
      plays a role in amnionitis. Fetal membranes were obtained during elective
      cesarean sections performed in full-term pregnancies of patients without systemic
      disease, signs of premature delivery, or fetal complications. Amniotic epithelial
      cells were isolated by trypsinization. The activin A concentrations in the
      culture media were measured by enzyme-linked immunosorbent assay, and cell
      proliferation was assessed by 5-bromo-2'-deoxyuridine incorporation. Amniotic
      epithelial cells secreted activin A in a cell density-dependent manner, and
      lipopolysaccharide (10  MU g/mL) enhanced the secretion at each cell density.
      Lipopolysaccharide (10-50  MU g/mL) also stimulated activin A secretion in a dose
      dependent manner. Contrary to the effect of activin A secretion,
      lipopolysaccharide inhibited cell proliferation in amniotic epithelial cells. The
      present study suggests that lipopolysaccharide stimulation of activin A secretion
      may be a mechanism in the pathogenesis of amnionitis. 

PMID- 23956747
TI  - Remodeling of autogenous bone grafts after osteotome sinus floor elevation
      assessed by limited cone beam computed tomography.
AB  - This study assessed the radiographic appearance of bone graft domes
      longitudinally after osteotome sinus floor elevation using cone beam computed
      tomography (CBCT). This study presents the radiological findings of a 6-month
      follow-up CBCT study in maxillary osteotome sinus floor elevation. We examined 52
      patients with a crestal bone height of less than 8 mm in the posterior maxilla
      who required sinus augmentation. Implants (n = 91) were subsequently placed in
      regenerated bone following osteotome sinus floor elevation; autogenous bone was
      used as the augmentation material. In all cases, the grafted augmentation
      material tended to be absorbed, but at least 1 mm of grafted augmentation
      material was recognized around the implant fixtures on CBCT at the second implant
      operation. The border between the grafted augmentation material and the existing
      bone was indistinct. The grafted area apical to the implants undergoes shrinkage
      and remodeling. It was suggested that sufficient grafted autogenous bone changes
      into bone to support an implant. 

PMID- 23956748
TI  - Investigation of Luminescence Characteristics of Osmium(II) Complexes in the
      Presence of Heparin Polyanions.
AB  - The luminescence characteristics of six osmium carbonyl complexes with
      phenanthroline (phen) or bipyridine (bpy) and pyridine (py), 4-phenylpyridine (4
      phpy), or triphenylphosphine (PPh3) complexes in the presence of polyanion
      heparin were studied in both ethanol and aqueous solutions. The influence of
      heparin on the luminescence of the complexes is heavily dependent on the type of
      ligands in the complexes and the solvent used. In the ethanol solutions, the
      heparin solution enhanced the luminescence of the five osmium complexes, with the
      strongest enhancement to the 4-phenylpyridine complexes; linear curves were
      obtained in the luminescence enhancement ratio (F/F 0) versus the heparin
      concentration range of 1-40  MU g/mL. In aqueous solutions, heparin quenching of
      the complexes was more significant; a linear quenching curve was obtained with
      [Os(phen)2CO(PPh3)](PF6)2 in the lower concentration range of 1-12  MU g/mL. The
      interaction of these complexes with heparin in the solutions is discussed. The
      complexes are shown to be successful in the fast and sensitive detection of
      heparin in commercial injectable samples. 

PMID- 23956749
TI  - A large cohort study of hypothyroidism and hyperthyroidism in relation to
      gynecologic cancers.
AB  - Background. Thyroid status may influence tumorigenesis of gynecologic cancers,
      yet epidemiologic studies of this relationship are limited and inconsistent.
      Methods. We evaluated the association of self-reported history of physician
      diagnosed hypothyroidism and hyperthyroidism with medical-record confirmed
      endometrial (EC; all invasive adenocarcinomas) and ovarian cancer (OC; epithelial
      ovarian or peritoneal cancers) in Nurses' Health Study (NHS) from 1976 to 2010
      and NHSII from 1989 to 2011. Cox proportional hazard models were used to estimate
      multivariable rate ratios (RRs) and 95% confidence intervals based on pooled
      cohort data. Results. We confirmed 1314 incident cases of EC and 1150 cases of
      OC. Neither a history of hypothyroidism nor hyperthyroidism was significantly
      associated with risk of EC or OC. However, having a history of hypothyroidism for
      8+ years (median) was nonsignificantly inversely associated with EC (RR = 0.81;
      95% CI = 0.63-1.04; P-trend with history duration = 0.11) and OC (RR = 0.87, 95%
      CI = 0.66-1.15; P-trend = 0.13). Having a history of hyperthyroidism for 6+ years
      (median) was non-significantly positively associated with EC (RR = 1.69; 95% CI =
      0.86-3.30; P-trend = 0.12) but not OC (RR = 1.12; 95% CI = 0.46-2.72; P-trend =
      0.95). Conclusions. A history of hypothyroidism or hyperthyroidism was not
      significantly associated with risk of EC or OC. 

PMID- 23956750
TI  - Aubergine and potato sensitivity with latex sensitisation and oral allergy
      syndrome.
AB  - Aubergine allergy is rare outside of India and the far east, and very few cases
      have been reported. We describe a case of aubergine allergy in a 9-year-old girl
      of Anglo-Indian descent who also had sensitivity to potato, coincidental oral
      allergy syndrome, and latex sensitisation with mild oral symptoms on consuming
      kiwi fruit. Specific IgE to aubergine was negative, but skin testing was positive
      to both raw and cooked aubergine. With early and increased consumption of exotic
      vegetables in western countries, more cases of aubergine allergy can be expected
      and negative blood tests do not exclude type 1 sensitivity. 

PMID- 23956751
TI  - Late onset anaphylaxis in a hydatid cyst case presenting with chronic urticaria.
AB  - Hydatid cyst is still endemic in various regions of the world. It is the most
      frequent cause of liver cysts worldwide. Urticaria is sometimes the first
      manifestation of the disease. However anaphylactic reaction and urticaria have
      been very rarely reported in the literature. Traditionally, surgery has been the
      only accepted mode of treatment; however, percutaneous treatment has recently
      been proposed as an alternative. Cases of anaphylaxis have been reported after
      percutaneous drainage of hydatid cyst. However, anaphylaxis usually develops
      within a few hours. Herein, we describe the case of a patient who presented with
      hydatid cyst causing chronic urticaria and late anaphylactic reaction following
      percutaneous aspiration of a liver hydatid cyst. We emphasize that physicians
      should be aware of hydatid cyst as a possible etiology for seemingly chronic
      spontaneous urticaria, especially in endemic regions. Patients should be kept
      under observation for at least one day due to the risk of early and late
      anaphylaxis after percutaneous aspiration treatment. 

PMID- 23956752
TI  - Respiratory Disease following Illicit Injection of Silicone: A Case Report.
AB  - Unregulated, pseudomedical procedures risk serious sequelae even when otherwise
      safe compounds are used. Silicone is commonly used legally in cosmetic procedures
      owing to its durability, resistance to heat and aging, and low immunogenicity.
      However, inappropriate or illegal silicone injection can pose severe local and
      systemic complications including serious pulmonary compromise. We describe the
      case of a 30-year-old female who presented with hemoptysis and progressive
      shortness of breath following illicit silicone injections to the gluteal fat and
      was found to have new, diffuse, bilateral, ground-glass opacities on contrast
      enhanced pulmonary computed tomography. Transbronchial biopsy elucidated that
      this was a lipoid pneumonia-type injury secondary to silicone infiltration. 

PMID- 23956753
TI  - Torsion of Wandering Gallbladder following Colonoscopy.
AB  - Torsion of the gallbladder is an uncommon condition that may present as an acute
      abdomen. Its preoperative diagnosis can often be challenging due to its variable
      presentation, with specific sonographic signs seen infrequently. We describe, to
      our knowledge, the first case of torsion of a wandering gallbladder following a
      colonoscopy in a 69-year-old female who presented with acute abdominal pain after
      procedure. This was discovered intraoperatively, and after a subsequent
      cholecystectomy, she had an uncomplicated recovery. 

PMID- 23956754
TI  - The christchurch earthquake: crush injury, neuropathic pain, and posttraumatic
      stress disorder.
AB  - On February 22, 2011, an earthquake of magnitude 6.3 struck Christchurch, New
      Zealand. The peak ground acceleration, a measure of the shaking or intensity of
      an earthquake, was one of the highest ever recorded worldwide. One hundred and
      eighty-five people lost their lives; many others were injured. Two cases both
      involving young women are presented; they sustained crush injuries to limbs after
      being trapped by falling debris and went on to develop severe neuropathic pain.
      This report examines the mechanisms of neuropathic pain in the setting of crush
      injury, the treatment modalities, and the association between chronic pain and
      posttraumatic stress disorder. These case reports highlight the fact that crush
      injury is relatively common during major earthquakes and that neuropathic pain is
      an important sequel of this. Post-traumatic stress disorder is common in
      earthquake survivors with a recognised association with chronic pain. Pain
      related disability may increase as well. Issues such as chronic pain and physical
      disability should not be overlooked as attention focuses on disaster management
      and the treatment of life-threatening injuries. 

PMID- 23956755
TI  - High-throughput Peptide epitope mapping using carbon nanotube field-effect
      transistors.
AB  - Label-free and real-time detection technologies can dramatically reduce the time
      and cost of pharmaceutical testing and development. However, to reach their full
      promise, these technologies need to be adaptable to high-throughput automation.
      To demonstrate the potential of single-walled carbon nanotube field-effect
      transistors (SWCNT-FETs) for high-throughput peptide-based assays, we have
      designed circuits arranged in an 8 * 12 (96-well) format that are accessible to
      standard multichannel pipettors. We performed epitope mapping of two HIV-1 gp160
      antibodies using an overlapping gp160 15-mer peptide library coated onto
      nonfunctionalized SWCNTs. The 15-mer peptides did not require a linker to adhere
      to the non-functionalized SWCNTs, and binding data was obtained in real time for
      all 96 circuits. Despite some sequence differences in the HIV strains used to
      generate these antibodies and the overlapping peptide library, respectively, our
      results using these antibodies are in good agreement with known data, indicating
      that peptides immobilized onto SWCNT are accessible and that linear epitope
      mapping can be performed in minutes using SWCNT-FET. 

PMID- 23956756
TI  - Personnel's health surveillance at work: effect of age, body mass index, and
      shift work on mental workload and work ability index.
AB  - INTRODUCTION: Two great changes in developed countries are taking place:
      populations are ageing and becoming increasingly overweight. Combination of these
      factors with shift work is a risk factor for work ability and mental workload
      that are dynamic processes which change greatly throughout an individual's work
      life. The aim of this study was to investigate mental workload and work ability
      in textile workers and to identify factors which affect work ability and mental
      workload. METHODS: This cross-sectional study was carried out among 194 male
      workers in textile industry. Employees based on their job group and work
      conditions have been divided into 6 categories. They completed work ability index
      and mental workload questionnaires during three work shifts. Body mass index
      (BMI) and demographic details were recorded. RESULTS: All of the participants
      rated their work ability as moderate with high mental workload. The mean WAI and
      mental workload in age group were significant. The mean BMI was 25.5 kg/m(2)
      (standard deviation 4.1) and the mean age was 40.22 years. There was a
      statistically significant correlation between work ability index and shift work.
      CONCLUSIONS: Unlike the previous study, a decrease point in WAI started in early
      age that may be due to life-style work and another psychological factor; on the
      other hand, NASA-TLX revealed high score in six subscales that can be another
      reason for low WAI.

PMID- 23956757
TI  - Measuring workplace travel behaviour: validity and reliability of survey
      questions.
AB  - BACKGROUND: The purpose of this study was to assess the (previously untested)
      reliability and validity of survey questions commonly used to assess travel mode
      and travel time. METHODS: Sixty-five respondents from a staff survey of travel
      behaviour conducted in a south-western Sydney hospital agreed to complete a
      travel diary for a week, wear an accelerometer over the same period, and twice
      complete an online travel survey an average of 21 days apart. The agreement in
      travel modes between the self-reported online survey and travel diary was
      examined with the kappa statistic. Spearman's correlation coefficient was used to
      examine agreement of travel time from home to workplace measured between the self
      reported online survey and four-day travel diary. Moderate-to-vigorous physical
      activity (MVPA) time of active and nonactive travellers was compared by t-test.
      RESULTS: There was substantial agreement between travel modes (K = 0.62, P <
      0.0001) and a moderate correlation for travel time (rho = 0.75, P < 0.0001)
      reported in the travel diary and online survey. There was a high level of
      agreement for travel mode (K = 0.82, P < 0.0001) and travel time (rho = 0.83, P <
      0.0001) between the two travel surveys. Accelerometer data indicated that for
      active travellers, 16% of the journey-to-work time is MVPA, compared with 6% for
      car drivers. Active travellers were significantly more active across the whole
      workday. CONCLUSIONS: The survey question "How did you travel to work this week?
      If you used more than one transport mode specify the one you used for the longest
      (distance) portion of your journey" is reliable over 21 days and agrees well with
      a travel diary.

PMID- 23956758
TI  - Cobenefits of replacing car trips with alternative transportation: a review of
      evidence and methodological issues.
AB  - It has been reported that motor vehicle emissions contribute nearly a quarter of
      world energy-related greenhouse gases and cause nonnegligible air pollution
      primarily in urban areas. Reducing car use and increasing ecofriendly alternative
      transport, such as public and active transport, are efficient approaches to
      mitigate harmful environmental impacts caused by a large amount of vehicle use.
      Besides the environmental benefits of promoting alternative transport, it can
      also induce other health and economic benefits. At present, a number of studies
      have been conducted to evaluate cobenefits from greenhouse gas mitigation
      policies. However, relatively few have focused specifically on the transport
      sector. A comprehensive understanding of the multiple benefits of alternative
      transport could assist with policy making in the areas of transport, health, and
      environment. However, there is no straightforward method which could estimate
      cobenefits effect at one time. In this paper, the links between vehicle emissions
      and air quality, as well as the health and economic benefits from alternative
      transport use, are considered, and methodological issues relating to the
      modelling of these cobenefits are discussed. 

PMID- 23956760
TI  - Heterozygous alterations of TNFRSF13B/TACI in tonsillar hypertrophy and
      sarcoidosis.
AB  - TNFRSF13B/TACI defects have been associated with CVID pathogenesis and/or
      phenotype, especially the development of benign lymphoproliferation and
      autoimmunity. Our purpose was to investigate the role of TNFRSF13B/TACI defects
      in the pathogenesis of two common lymphoproliferative disorders, namely,
      sarcoidosis and tonsillar hypertrophy (TH). 105 patients (71 with sarcoidosis and
      34 with TH, including 19 without infectious causative and 15 due to Haemophilus
      influenzae) were analyzed for TNFRSF13B/TACI defects. Two out of 19 TH patients
      without infectious cause (10.5%) and 2 patients with sarcoidosis (2.8%) displayed
      rare TNFRSF13B/TACI defects (I87N, L69TfsX12, E36L, and R202H, resp.). Both
      mutations identified in TH patients have been assessed as deleterious for protein
      function, while the patient with the R202H mutation and sarcoidosis exhibited
      also sIgG4D. Our study further supports the notion that TNFRSF13B/TACI defects
      alone do not result in CVID but may be also found frequently in distinct clinical
      phenotypes, including benign lymphoproliferation and IgG subclass deficiencies. 

PMID- 23956759
TI  - IL-17A and Th17 cells in lung inflammation: an update on the role of Th17 cell
      differentiation and IL-17R signaling in host defense against infection.
AB  - The significance of Th17 cells and interleukin- (IL-)17A signaling in host
      defense and disease development has been demonstrated in various infection and
      autoimmune models. Numerous studies have indicated that Th17 cells and its
      signature cytokine IL-17A are critical to the airway's immune response against
      various bacteria and fungal infection. Cytokines such as IL-23, which are
      involved in Th17 differentiation, play a critical role in controlling Klebsiella
      pneumonia (K. pneumonia) infection. IL-17A acts on nonimmune cells in infected
      tissues to strengthen innate immunity by inducing the expression of antimicrobial
      proteins, cytokines, and chemokines. Mice deficient in IL-17 receptor (IL-17R)
      expression are susceptible to infection by various pathogens. In this review, we
      summarize the recent advances in unraveling the mechanism behind Th17 cell
      differentiation, IL-17A/IL-17R signaling, and also the importance of IL-17A in
      pulmonary infection. 

PMID- 23956761
TI  - The role of the immune system in Huntington's disease.
AB  - Huntington's disease (HD) is characterized by a progressive course of disease
      until death 15-20 years after the first symptoms occur and is caused by a
      mutation with expanded CAG repeats in the huntingtin (htt) protein. Mutant htt
      (mhtt) in the striatum is assumed to be the main reason for neurodegeneration.
      Knowledge about pathophysiology has rapidly improved discussing influences of
      excitotoxicity, mitochondrial damage, free radicals, and inflammatory mechanisms.
      Both innate and adaptive immune systems may play an important role in HD.
      Activation of microglia with expression of proinflammatory cytokines, impaired
      migration of macrophages, and deposition of complement factors in the striatum
      indicate an activation of the innate immune system. As part of the adaptive
      immune system, dendritic cells (DCs) prime T-cell responses secreting
      inflammatory mediators. In HD, DCs may contain mhtt which brings the adaptive
      immune system into the focus of interest. These data underline an increasing
      interest in the peripheral immune system for pathomechanisms of HD. It is still
      unclear if neuroinflammation is a reactive process or if there is an active
      influence on disease progression. Further understanding the influence of
      inflammation in HD using mouse models may open various avenues for promising
      therapeutic approaches aiming at slowing disease progression or forestalling
      onset of disease. 

PMID- 23956762
TI  - LPS-induced inflammation potentiates the IL-1beta-mediated reduction of LH
      secretion from the anterior pituitary explants.
AB  - Acting at the level of the brain, interleukin- (IL-)1 beta is considered to be
      one of the most potent downregulators of reproduction processes during
      immune/inflammatory challenge. IL-1 beta suppresses gonadotropin-releasing
      hormone (GnRH) secretion from the hypothalamus resulting in the inhibition of the
      luteinizing hormone (LH) release from the anterior pituitary (AP). However, the
      presence of IL-1 beta receptors in the AP suggests the possible direct action of
      this cytokine on LH secretion. The study was designed to determine the effect of
      IL-1 beta on the LH secretion from the AP explants collected from saline and LPS
      treated ewes in the follicular phase. It was found that IL-1 beta suppressed (P
      <= 0.01) GnRH-stimulated LH release and LH beta gene expression in AP explants in
      both groups. However, IL-1 beta action was more potent in the explants collected
      from LPS-treated animals. Pituitaries from LPS-treated animals were characterized
      by increased (P <= 0.01) IL-1 type I receptor and decreased (P <= 0.01) GnRH
      receptor gene expression level compared to the saline-treated group. IL-1 beta
      also affected the GnRH-R gene expression in explants collected from LPS-treated
      animals. Our results show that direct action of IL-1 beta on the pituitary
      gonadotropes could be one of the reasons of the reproductive processes disorders
      accompanying an inflammatory state. 

PMID- 23956764
TI  - Different Effects of Six Antibiotics and Ten Traditional Chinese Medicines on
      Shiga Toxin Expression by Escherichia coli O157:H7.
AB  - This study compared the effects of ten types of traditional Chinese medicines
      (TCMs) and six different antibiotics on E. coli O157:H7 Shiga toxin gene (stx2)
      mRNA expression level based on real-time PCR and the expression level of Stx
      toxin using an ELISA quantitative assay. We also compared their effects on the
      induction of the SOS response. The results clearly indicated that all ten TCMs
      had negative results in the SOS response induction test, while most TCMs did not
      increase the levels of stx2 mRNA and the Stx toxin. Some TCMs did increase the
      mRNA levels of the stx2 gene and the Stx toxin level, but their increases were
      much lower than those caused by antibiotics. With the exception of cefotaxime,
      the six antibiotics increased the Stx toxin level and increased the stx2 gene
      mRNA level. With the exceptions of cefotaxime and tetracycline, the antibiotics
      increased the SOS induction response. These results suggest that TCMs may have
      advantages compared with antibiotics, when treating E. coli O157:H7; TCMs did not
      greatly increase Stx toxin production and release. 

PMID- 23956765
TI  - Panax Quinquefolius Saponin of Stem and Leaf Attenuates Intermittent High Glucose
      Induced Oxidative Stress Injury in Cultured Human Umbilical Vein Endothelial
      Cells via PI3K/Akt/GSK-3 beta Pathway.
AB  - Panax quinquefolius saponin of stem and leaf (PQS), the effective parts of
      American ginseng, is widely used in China as a folk medicine for diabetes and
      cardiovascular diseases treatment. In our previous studies, we have demonstrated
      that PQS could improve the endothelial function of type II diabetes mellitus
      (T2DM) rats with high glucose fluctuation. In the present study, we investigated
      the protective effects of PQS against intermittent high glucose-induced oxidative
      damage on human umbilical vein endothelial cells (HUVECs) and the role of
      phosphatidylinositol 3-kinase kinase (PI3K)/Akt/GSK-3 beta pathway involved. Our
      results suggested that exposure of HUVECs to a high glucose concentration for 8
      days showed a great decrease in cell viability accompanied by marked MDA content
      increase and SOD activity decrease. Moreover, high glucose significantly reduced
      the phosphorylation of Akt and GSK-3 beta . More importantly, these effects were
      even more evident in intermittent high glucose condition. PQS treatment
      significantly attenuated intermittent high glucose-induced oxidative damage on
      HUVECs and meanwhile increased cell viability and phosphorylation of Akt and GSK
      3 beta of HUVECs. Interestingly, all these reverse effects of PQS on intermittent
      high glucose-cultured HUVECs were inhibited by PI3K inhibitor LY294002. These
      findings suggest that PQS attenuates intermittent-high-glucose-induced oxidative
      stress injury in HUVECs by PI3K/Akt/GSK-3 beta pathway. 

PMID- 23956766
TI  - The reporting quality assessment of complex interventions' articles in
      traditional chinese medicine.
AB  - Objective. To realize the current situation and problems of complex
      interventions' clinical trials. Methods. Searching at Chinese Journal Integrated
      Traditional and Western Medicine and Journal of Traditional Chinese Medicine from
      2007 to 2012 by hand, we identified complex interventions' articles, and then we
      used the proposed criteria of complex interventions and CONSORT FOR TCM to
      evaluate. Results. All data is presented as counts with percentages and details
      in tables. Conclusion. Our evaluation presented that complex interventions have
      many defects: the selection of the intervention's components lacks rationale,
      complex interventions were short of fundamental researches, components'
      interactions were ambiguous, and the advantages of complex interventions were not
      mentioned. Furthermore, explanation of sample size, blind, quality control,
      ethical approval, and inform consent were neglected in different degrees. 

PMID- 23956763
TI  - Pivotal roles of T-helper 17-related cytokines, IL-17, IL-22, and IL-23, in
      inflammatory diseases.
AB  - T-helper 17 (Th17) cells are characterized by producing interleukin-17 (IL-17,
      also called IL-17A), IL-17F, IL-21, and IL-22 and potentially TNF- alpha and IL-6
      upon certain stimulation. IL-23, which promotes Th17 cell development, as well as
      IL-17 and IL-22 produced by the Th17 cells plays essential roles in various
      inflammatory diseases, such as experimental autoimmune encephalomyelitis,
      rheumatoid arthritis, colitis, and Concanavalin A-induced hepatitis. In this
      review, we summarize the characteristics of the functional role of Th17 cells,
      with particular focus on the Th17 cell-related cytokines such as IL-17, IL-22,
      and IL-23, in mouse models and human inflammatory diseases. 

PMID- 23956767
TI  - Traditional herbal medicine: a review of potential of inhibitory hepatocellular
      carcinoma in basic research and clinical trial.
AB  - Although significantly develops in hepatocellular carcinoma (HCC), features of
      HCC remain an aggressive cancer with a dismal outcome. Traditional Chinese
      medicine (TCM), specifically Chinese herbal medicine (CHM), is one of the most
      popular complementary and alternative medicine modalities worldwide. The use of
      heat-clearing and detoxicating (Chinese named qingre jiedu) CHM has attracted
      great attention as an alternative antitumor including HCC considering its low
      toxicity and high activity. Together these reports indicate that CHM is a
      promising anti-HCC herbal remedy in basic research. For patients with advanced
      HCC, CHM including formula and single combined with transcatheter arterial
      chemoembolization or chemotherapy is able to decrease tumor growth and the side
      effect of toxicity and improve overall survival, quality of life, and immune
      function. Due to its abundance, low cost, and safety in consumption, CHM remains
      a species with tremendous potential for further investigation in HCC. 

PMID- 23956769
TI  - Network analysis of acupuncture points used in the treatment of low back pain.
AB  - Background. The appropriate selection of acupoints is fundamental to obtain a
      therapeutic effect from clinical acupuncture. Objective. Using a network analysis
      method, we investigated the acupoints that are combined to treat low back pain
      (LBP). Methods. To analyze the patterns of the combinations of acupoints, we used
      acupoint information from clinical trials to calculate the modified mutual
      information (MI) value, integrated these data, and visualized the network.
      Results. Based on the highest MI values, we found two different types of acupoint
      pairs used in the treatment of LBP: pairs of distant acupoints and pairs of local
      acupoints. Using modular analysis, we found that three acupoint modules were
      applied in the treatment of LBP: local acupoints, distant acupoints along the
      meridian, and distant acupoints based on the symptom differentiations.
      Conclusion. Using the modified MI technique, we provide a systematic framework
      for the acupoint combination network, and reveal how the technique of acupoint
      combination is used in the treatment of LBP. Application of this knowledge in
      acupuncture research may help clarify the mechanisms underlying acupuncture
      treatment at the systems level, bridging the gap between traditional medicine and
      modern science. 

PMID- 23956768
TI  - Therapeutic applications of herbal medicines for cancer patients.
AB  - Medicinal herbs and their derivative phytocompounds are being increasingly
      recognized as useful complementary treatments for cancer. A large volume of
      clinical studies have reported the beneficial effects of herbal medicines on the
      survival, immune modulation, and quality of life (QOL) of cancer patients, when
      these herbal medicines are used in combination with conventional therapeutics.
      Here, we briefly review some examples of clinical studies that investigated the
      use of herbal medicines for various cancers and the development of randomized
      controlled trials (RCTs) in this emerging research area. In addition, we also
      report recent studies on the biochemical and cellular mechanisms of herbal
      medicines in specific tumor microenvironments and the potential application of
      specific phytochemicals in cell-based cancer vaccine systems. This review should
      provide useful technological support for evidence-based application of herbal
      medicines in cancer therapy. 

PMID- 23956770
TI  - Antipoliovirus Activity of the Organic Extract of Eupatorium buniifolium:
      Isolation of Euparin as an Active Compound.
AB  - The antiviral activity of the organic extract (OE) of Eupatorium buniifolium
      against poliovirus type 1 was determined by in vitro assays with an effective
      concentration 50 (EC50) of 23.3 +/- 3.3 ug/mL. Bioassay-guided fractionation of
      the OE allowed the isolation of an active principle that was identified by
      spectroscopic methods ((1)H- and (13)C-NMR, EI-MS, UV, and IR spectroscopy) as
      the benzofuran euparin. The plaque reduction assay in Vero cells was used to
      assess the antiviral activity of euparin against poliovirus types 1, 2, and 3
      with EC50 values of 0.47, 0.12, and 0.15 ug/mL, respectively. Moreover, this
      compound showed high selectivity indexes of 284.9, 1068, and 854.7, respectively.
      In order to identify the mechanism by which euparin exerts its antiviral
      activity, the virucidal effect, the pretreatment of Vero cells, and the time of
      action on one viral replication cycle were evaluated. Results obtained
      demonstrated that euparin exerts its effect during the early events of the
      replication cycle, from the virus adsorption to cells up to the first twenty
      minutes after infection. This is the first report on the presence of euparin in
      E. buniifolium and its antiviral activity. 

PMID- 23956772
TI  - Ocotillol Enhanced the Antitumor Activity of Doxorubicin via p53-Dependent
      Apoptosis.
AB  - The use of doxorubicin (Dox) was severely constrained by dose-dependent side
      effects, which might be attenuated by combining a "sensitizer" to decrease its
      cumulative dosage. In this study, it was investigated whether ocotillol could
      enhance the antiproliferation activity of Dox. MTT assays and xenograft tumor
      model were firstly conducted to evaluate the effect of ocotillol on the antitumor
      activity of Dox. Flow cytometry and Hoechst staining assays were then performed
      to assess cell apoptosis. Western blot and real-time PCR were finally used to
      detect the expression of p53 and its target genes. Our results showed ocotillol
      to enhance Dox-induced cell death in p53 wild-type cancer cells. Compared with
      Dox alone, Dox with ocotillol (Dox-O) could induce much more cell apoptosis and
      activate p53 to a much greater degree, which in turn markedly increased
      expression of proapoptosis genes. The enhanced cytotoxic activity was partially
      blocked by pifithrin- alpha , which might be through attenuating the increased
      apoptosis. Furthermore, ocotillol significantly increased the antitumor activity
      of Dox in A549 xenograft tumor in nude mice. These findings indicated that
      ocotillol could potentiate the cytotoxic effect of Dox through p53-dependent
      apoptosis and suggested that coadministration of ocotillol with Dox might be a
      potential therapeutic strategy. 

PMID- 23956771
TI  - Curcumin pretreatment prevents potassium dichromate-induced hepatotoxicity,
      oxidative stress, decreased respiratory complex I activity, and membrane
      permeability transition pore opening.
AB  - Curcumin is a polyphenol derived from turmeric with recognized antioxidant
      properties. Hexavalent chromium is an environmental toxic and carcinogen compound
      that induces oxidative stress. The objective of this study was to evaluate the
      potential protective effect of curcumin on the hepatic damage generated by
      potassium dichromate (K2Cr2O7) in rats. Animals were pretreated daily by 9-10
      days with curcumin (400 mg/kg b.w.) before the injection of a single
      intraperitoneal of K2Cr2O7 (15 mg/kg b.w.). Groups of animals were sacrificed 24
      and 48 h later. K2Cr2O7-induced damage to the liver was evident by histological
      alterations and increase in the liver weight and in the activity of alanine
      aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline
      phosphatase in plasma. In addition, K2Cr2O7 induced oxidative damage in liver and
      isolated mitochondria, which was evident by the increase in the content of
      malondialdehyde and protein carbonyl and decrease in the glutathione content and
      in the activity of several antioxidant enzymes. Moreover, K2Cr2O7 induced
      decrease in mitochondrial oxygen consumption, in the activity of respiratory
      complex I, and permeability transition pore opening. All the above-mentioned
      alterations were prevented by curcumin pretreatment. The beneficial effects of
      curcumin against K2Cr2O7-induced liver oxidative damage were associated with
      prevention of mitochondrial dysfunction. 

PMID- 23956773
TI  - Chinese Medicines as an Adjuvant Therapy for Unresectable Hepatocellular
      Carcinoma during Transarterial Chemoembolization: A Meta-Analysis of Randomized
      Controlled Trials.
AB  - Objective. To conduct a comprehensive PRISMA-compliant systematic review and meta
      analysis to evaluate the efficacy and safety of Chinese medicines (CMs) as an
      adjuvant therapy for unresectable HCC during transarterial chemoembolization
      (TACE). Methods. Main databases were searched up to October 2012 for randomized
      controlled trials (RCTs) evaluating the effects of CMs plus TACE on unresectable
      HCC compared with TACE alone. References of relevant reviews and eligible studies
      were also assessed. Risk ratios with 95% confidence intervals and mean difference
      were calculated. Heterogeneity and publication bias were examined. Results. Sixty
      seven trials (N = 5,211) were included in the meta-analysis. Sensitivity analysis
      and random-effects model were performed for assessing significant heterogeneity.
      CMs plus TACE showed beneficial effects on tumor response, survival at 6, 12, 18,
      24, and 36 months, quality of life, and TACE toxicity reduction compared with
      TACE alone. Conclusion. The results show that the use of CMs may increase the
      efficacy and reduce the toxicity of TACE in treating patients with unresectable
      HCC. These findings suggest that CMs could be considered as an adjuvant therapy
      for unresectable HCC patients during TACE. Larger-scale RCTs using standard
      methods and long-term follow-up are warranted to confirm these findings. 

PMID- 23956774
TI  - The medical necessity for medicinal cannabis: prospective, observational study
      evaluating the treatment in cancer patients on supportive or palliative care.
AB  - Background. Cancer patients using cannabis report better influence from the plant
      extract than from synthetic products. However, almost all the research conducted
      to date has been performed with synthetic products. We followed patients with a
      medicinal cannabis license to evaluate the advantages and side effects of using
      cannabis by cancer patients. Methods. The study included two interviews based on
      questionnaires regarding symptoms and side effects, the first held on the day the
      license was issued and the second 6-8 weeks later. Cancer symptoms and cannabis
      side effects were documented on scales from 0 to 4 following the CTCAE. The
      distress thermometer was used also. Results. Of the 211 patients who had a first
      interview, only 131 had the second interview, 25 of whom stopped treatment after
      less than a week. All cancer or anticancer treatment-related symptoms showed
      significant improvement (P < 0.001). No significant side effects except for
      memory lessening in patients with prolonged cannabis use (P = 0.002) were noted.
      Conclusion. The positive effects of cannabis on various cancer-related symptoms
      are tempered by reliance on self-reporting for many of the variables. Although
      studies with a control group are missing, the improvement in symptoms should push
      the use of cannabis in palliative treatment of oncology patients. 

PMID- 23956776
TI  - Validation of antimycobacterial plants used by traditional healers in three
      districts of the limpopo province (South Africa).
AB  - The aim of the study was to scientifically evaluate the antimycobacterial
      activity of selected indigenous medicinal plants from the Limpopo Province used
      for the treatment of humans with symptoms of Mycobacterium tuberculosis. The
      leaves of five plant species (Apodytes dimidiata, Artemisia, Combretum
      hereroense, Lippia javanica, and Zanthoxylum capense) were collected from the
      Lowveld National Botanical Garden in Nelspruit, South Africa. The dried leaves
      were powdered and extracted using hexane, dichloromethane, acetone, and methanol.
      Antimycobacterial activity was evaluated using microdilution assay and
      bioautography and rho -iodonitrotetrazolium violet (INT) as indicator.
      Antioxidant activities were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH).
      Phytochemical content of extracts was further evaluated. The acetone extracts of
      L. javanica displayed antioxidant activity on BEA chromatogram. T Acetone
      extracts of A. afra had MIC value of 0.39 mg/mL against Mycobacterium smegmatis
      ATCC 1441. Acetone extracts of C. hereroense and L. javanica had MIC value of
      0.47 mg/mL. Four bands that inhibited the growth of M. smegmatis were observed at
      R f values of 0.12, 0.63, and 0.87 on BEA and 0.73 on EMW. The plant species A.
      dimidiata, A. afra, C. hereroense, and L. javanica in this study demonstrated
      their potential as sources of anti-TB drug leads. 

PMID- 23956775
TI  - On the g-protein-coupled receptor heteromers and their allosteric receptor
      receptor interactions in the central nervous system: focus on their role in pain
      modulation.
AB  - The modulatory role of allosteric receptor-receptor interactions in the pain
      pathways of the Central Nervous System and the peripheral nociceptors has become
      of increasing interest. As integrators of nociceptive and antinociceptive wiring
      and volume transmission signals, with a major role for the opioid receptor
      heteromers, they likely have an important role in the pain circuits and may be
      involved in acupuncture. The delta opioid receptor (DOR) exerts an antagonistic
      allosteric influence on the mu opioid receptor (MOR) function in a MOR-DOR
      heteromer. This heteromer contributes to morphine-induced tolerance and
      dependence, since it becomes abundant and develops a reduced G-protein-coupling
      with reduced signaling mainly operating via beta -arrestin2 upon chronic morphine
      treatment. A DOR antagonist causes a return of the Gi/o binding and coupling to
      the heteromer and the biological actions of morphine. The gender- and ovarian
      steroid-dependent recruitment of spinal cord MOR/kappa opioid receptor (KOR)
      heterodimers enhances antinociceptive functions and if impaired could contribute
      to chronic pain states in women. MOR1D heterodimerizes with gastrin-releasing
      peptide receptor (GRPR) in the spinal cord, mediating morphine induced itch.
      Other mechanism for the antinociceptive actions of acupuncture along meridians
      may be that it enhances the cross-desensitization of the TRPA1 (chemical
      nociceptor)-TRPV1 (capsaicin receptor) heteromeric channel complexes within the
      nociceptor terminals located along these meridians. Selective ionotropic
      cannabinoids may also produce cross-desensitization of the TRPA1-TRPV1
      heteromeric nociceptor channels by being negative allosteric modulators of these
      channels leading to antinociception and antihyperalgesia. 

PMID- 23956777
TI  - Parkia speciosa Hassk.: A Potential Phytomedicine.
AB  - Parkia speciosa Hassk., or stink bean, is a plant indigenous to Southeast Asia.
      It is consumed either raw or cooked. It has been used in folk medicine to treat
      diabetes, hypertension, and kidney problems. It contains minerals and vitamins.
      It displays many beneficial properties. Its extracts from the empty pods and
      seeds have a high content of total polyphenol, phytosterol, and flavonoids. It
      demonstrates a good antioxidant activity. Its hypoglycemic effect is reported to
      be attributable to the presence of beta -sitosterol, stigmasterol, and stigmast-4
      en-3-one. The cyclic polysulfide compounds exhibit antibacterial activity, while
      thiazolidine-4-carboxylic acid possesses anticancer property. The pharmacological
      properties of the plant extract are described in this review. With ongoing
      research conducted on the plant extracts, Parkia speciosa has a potential to be
      developed as a phytomedicine. 

PMID- 23956778
TI  - Influence of the deqi sensation by suspended moxibustion stimulation in lumbar
      disc herniation: study for a multicenter prospective two arms cohort study.
AB  - Moxibustion stimulates the Deqi (Qi arrival) phenomenon. Many clinical
      observations have documented that the character of the Deqi was a composite heat
      sensitive moxibustion sensation. In this prospective multicentre comparative
      observational nonrandomized study, 92 patients with moderate to severe LDH were
      included. This study consisted of two parallel arms (A: heat-sensitive
      moxibustion sensation group; B: nonheat-sensitive moxibustion sensation group).
      Moxibustion was applied in the following three acupuncture points simultaneously:
      Da Changshu (BL25), Wei Zhong (BL40), and A-Shi acupuncture point (tenderness).
      The adjusted mean total Modified-JOA score showed significant differences between
      the groups in the first week (10.32 +/- 4.27 95% CI [9.23 ~ 11.40] versus control
      group 12.42 +/- 5.02 [11.62 ~ 13.69], P = 0.03). The outcome in the second week
      also presented significant differences in both groups (7.62 +/- 4.80 [6.46 ~
      8.77] versus 10.56 +/- 4.75 [9.35 ~ 11.76], P = 0.005). Significant differences
      were also manifested in the follow-up period (P = 0.007). It can be inferred that
      the existence of the Deqi (heat-sensitive moxibustion sensation) phenomenon in
      the process of suspended moxibustion is closely related to the curative effect,
      and arrival of heat-sensitive moxibustion sensation could improve the clinical
      curative effect of moxibustion. 

PMID- 23956779
TI  - Aspects of spirituality in medical doctors and their relation to specific views
      of illness and dealing with their patients' individual situation.
AB  - We intended to analyse which aspects of spirituality are of relevance for medical
      doctors in a mostly secular society and how their spiritual/religious attitudes
      are related to specific views of illness, their dealing with patients' individual
      situation, and finally physicians' life satisfaction. Data from an anonymous
      survey enrolling 237 medical doctors from Germany (mean age 45.7 +/- 9.6, 58%
      male, 42% female) indicated that secular forms of spirituality scored highest,
      while specific religious orientation had the lowest scores. Physicians with a
      specific specialization in complementary/alternative medicine (CAM) or
      anthroposophic medicine differed from their conventional counterparts with
      respect to specific aspects of spirituality; however, the specific views
      associated with these specialisations were only weakly to moderately correlated
      with physicians' view on the meaning of illness and how they assume that they
      would deal with their patients' individual situation. Of interest, the specific
      aspects of spirituality were negatively correlated with the view of "illness as a
      meaningless interruption" of life, indicating that physicians with a spiritual
      attitude would see illness also as a chance for an "individual development" and
      associated with a "biographical meaning" rather than just a "useless
      interruption" of life. 

PMID- 23956781
TI  - Xiao-Ai-Ping, a TCM Injection, Enhances the Antigrowth Effects of Cisplatin on
      Lewis Lung Cancer Cells through Promoting the Infiltration and Function of CD8(+)
      T Lymphocytes.
AB  - Objectives. To investigate how Xiao-Ai-Ping injection, a traditional Chinese
      medicine and an ancillary drug in tumor treatment, enhances the antitumor effects
      of cisplatin on Lewis lung cancer (LLC) cells. Methods. LLC-bearing mice were
      daily intraperitoneally injected with various doses of cisplatin, Xiao-Ai-Ping,
      or cisplatin plus Xiao-Ai-Ping, respectively. Body weight and tumor volumes were
      measured every three days. Results. Combination of Xiao-Ai-Ping and cisplatin
      yielded significantly better antigrowth and proapoptotic effects on LLC
      xenografts than sole drug treatment did. In addition, we found that Xiao-Ai-Ping
      triggered the infiltration of CD8(+) T cells, a group of cytotoxic T cells, to
      LLC xenografts. Furthermore, the mRNA levels of interferon- gamma (ifn- gamma ),
      perforin-1 (prf-1), and granzyme B (gzmb) in CD8(+) T cells were significantly
      increased after combination treatment of Xiao-Ai-Ping and cisplatin. In vitro
      studies showed that Xiao-Ai-Ping markedly upregulated the mRNA levels of ifn-
      gamma , prf-1, and gzmb in CD8(+) T cells in a concentration-dependent manner,
      suggesting that Xiao-Ai-Ping augments the function of CD8(+) T cells.
      Conclusions. Xiao-Ai-Ping promotes the infiltration and function of CD8(+) T
      cells and thus enhances the antigrowth effects of cisplatin on LLC xenografts,
      which provides new evidence for the combination of Xiao-Ai-Ping and cisplatin in
      clinic in China. 

PMID- 23956782
TI  - Integrating complementary and alternative medicine with primary health care.

PMID- 23956783
TI  - Identification of a Calcium Signalling Pathway of S-[6]-Gingerol in HuH-7 Cells.
AB  - Calcium signals in hepatocytes control cell growth, proliferation, and death.
      Members of the transient receptor potential (TRP) cation channel superfamily are
      candidate calcium influx channels. NF kappa B activation strictly depends on
      calcium influx and often induces antiapoptotic genes favouring cell survival.
      Previously, we reported that S-[6]-gingerol is an efficacious agonist of the
      transient receptor potential cation channel subfamily V member 1 (TRPV1) in
      neurones. In this study, we tested the effect of S-[6]-gingerol on HuH-7 cells
      using the Fluo-4 calcium assay, RT-qPCR, transient cell transfection, and
      luciferase measurements. We found that S-[6]-gingerol induced a transient rise in
      [Ca(2+)] i in HuH-7 cells. The increase in [Ca(2+)] i induced by S-[6]-gingerol
      was abolished by preincubation with EGTA and was also inhibited by the TRPV1
      channel antagonist capsazepine. Expression of TRPV1 in HuH-7 cells was confirmed
      by mRNA analysis as well as a test for increase of [Ca(2+)] i by TRPV1 agonist
      capsaicin and its inhibition by capsazepine. We found that S-[6]-gingerol induced
      rapid NF kappa B activation through TRPV1 in HuH-7 cells. Furthermore, S-[6]
      gingerol-induced NF kappa B activation was dependent on the calcium gradient and
      TRPV1. The rapid NF kappa B activation by S-[6]-gingerol was associated with an
      increase in mRNA levels of NF kappa B-target genes: cIAP-2, XIAP, and Bcl-2 that
      encode antiapoptotic proteins. 

PMID- 23956784
TI  - Distributions of usage and the costs of conventional medicine and traditional
      chinese medicine for lung cancer patients in taiwan.
AB  - Background. This study aims to analyze the utilization patterns of patients with
      lung cancer stratified by surgery status. Methods. A retrospective cohort study
      was conducted from 1996 to 2010 by using the Longitudinal Health Insurance
      Database 2005. Results. Among the 7,677 lung cancer patients, 230 (31.17%) and
      1,826 (26.32%) who have and have not undergone surgery have used TCM outpatient
      services, respectively. For lung cancer patients who have not undergone surgery,
      patients who are aged 70 years and older, males, occupational members, and
      farmers and fishermen are less likely to avail of TCM services. For lung cancer
      patients who have undergone surgery, the likelihood of TCM users is higher in
      residents who used TCM one year prior to lung cancer diagnosis and in patients
      with insurance amounts ranging from >=NT$60,000. The total amount paid per visit
      for WM is higher than that for one year of TCM outpatient care before and after
      lung cancer diagnosis. Conclusion. The factors associated with TCM use varied
      according to surgery status. The costs of insurance covering TCM were
      consistently lower than those covering WM for lung cancer patients. These
      findings would be useful for health policy makers who are considering TCM and WM
      integration. 

PMID- 23956786
TI  - Wavelet-based artifact identification and separation technique for EEG signals
      during galvanic vestibular stimulation.
AB  - We present a new method for removing artifacts in electroencephalography (EEG)
      records during Galvanic Vestibular Stimulation (GVS). The main challenge in
      exploiting GVS is to understand how the stimulus acts as an input to brain. We
      used EEG to monitor the brain and elicit the GVS reflexes. However, GVS current
      distribution throughout the scalp generates an artifact on EEG signals. We need
      to eliminate this artifact to be able to analyze the EEG signals during GVS. We
      propose a novel method to estimate the contribution of the GVS current in the EEG
      signals at each electrode by combining time-series regression methods with
      wavelet decomposition methods. We use wavelet transform to project the recorded
      EEG signal into various frequency bands and then estimate the GVS current
      distribution in each frequency band. The proposed method was optimized using
      simulated signals, and its performance was compared to well-accepted artifact
      removal methods such as ICA-based methods and adaptive filters. The results show
      that the proposed method has better performance in removing GVS artifacts,
      compared to the others. Using the proposed method, a higher signal to artifact
      ratio of -1.625 dB was achieved, which outperformed other methods such as ICA
      based methods, regression methods, and adaptive filters. 

PMID- 23956785
TI  - The case for immunomodulatory approaches in treating HSV encephalitis.
AB  - HSV encephalitis (HSE) is the most prevalent sporadic viral encephalitis.
      Although safe and effective antiviral therapies and greatly improved noninvasive
      diagnostic procedures have significantly improved outcomes, mortality (~20%) and
      debilitating neurological sequelae in survivors remain unacceptably high. An
      encouraging new development is that the focus is now shifting away from the virus
      exclusively, to include consideration of the host immune response to infection in
      the pathology underlying development of HSE. In this article, the authors discuss
      results from recent studies in experimental mouse models, as well as clinical
      reports that demonstrate a role for exaggerated host inflammatory responses in
      the brain in the development of HSE that is motivating researchers and clinicians
      to consider new therapeutic approaches for treating HSE. The authors also discuss
      results from a few studies that have shown that immunomodulatory drugs can be
      highly protective against HSE, which supports a role for deleterious host
      inflammatory responses in HSE. The impressive outcomes of some immunomodulatory
      approaches in mouse models of HSE emphasize the urgent need for clinical trials
      to rigorously evaluate combination antiviral and immunomodulatory therapy in
      comparison with standard antiviral therapy for treatment of HSE, and support for
      such an initiative is gaining momentum.

PMID- 23956787
TI  - Constructing benchmark databases and protocols for medical image analysis:
      diabetic retinopathy.
AB  - We address the performance evaluation practices for developing medical image
      analysis methods, in particular, how to establish and share databases of medical
      images with verified ground truth and solid evaluation protocols. Such databases
      support the development of better algorithms, execution of profound method
      comparisons, and, consequently, technology transfer from research laboratories to
      clinical practice. For this purpose, we propose a framework consisting of
      reusable methods and tools for the laborious task of constructing a benchmark
      database. We provide a software tool for medical image annotation helping to
      collect class label, spatial span, and expert's confidence on lesions and a
      method to appropriately combine the manual segmentations from multiple experts.
      The tool and all necessary functionality for method evaluation are provided as
      public software packages. As a case study, we utilized the framework and tools to
      establish the DiaRetDB1 V2.1 database for benchmarking diabetic retinopathy
      detection algorithms. The database contains a set of retinal images, ground truth
      based on information from multiple experts, and a baseline algorithm for the
      detection of retinopathy lesions. 

PMID- 23956788
TI  - Uses of phage display in agriculture: sequence analysis and comparative modeling
      of late embryogenesis abundant client proteins suggest protein-nucleic acid
      binding functionality.
AB  - A group of intrinsically disordered, hydrophilic proteins-Late Embryogenesis
      Abundant (LEA) proteins-has been linked to survival in plants and animals in
      periods of stress, putatively through safeguarding enzymatic function and
      prevention of aggregation in times of dehydration/heat. Yet despite decades of
      effort, the molecular-level mechanisms defining this protective function remain
      unknown. A recent effort to understand LEA functionality began with the unique
      application of phage display, wherein phage display and biopanning over
      recombinant Seed Maturation Protein homologs from Arabidopsis thaliana and
      Glycine max were used to retrieve client proteins at two different temperatures,
      with one intended to represent heat stress. From this previous study, we
      identified 21 client proteins for which clones were recovered, sometimes
      repeatedly. Here, we use sequence analysis and homology modeling of the client
      proteins to ascertain common sequence and structural properties that may
      contribute to binding affinity with the protective LEA protein. Our methods
      uncover what appears to be a predilection for protein-nucleic acid interactions
      among LEA client proteins, which is suggestive of subcellular residence. The
      results from this initial computational study will guide future efforts to
      uncover the protein protective mechanisms during heat stress, potentially leading
      to phage-display-directed evolution of synthetic LEA molecules. 

PMID- 23956790
TI  - Real-time in vivo computed optical interferometric tomography.
AB  - High-resolution real-time tomography of scattering tissues is important for many
      areas of medicine and biology1-6. However, the compromise between transverse
      resolution and depth-of-field in addition to low sensitivity deep in tissue
      continue to impede progress towards cellular-level volumetric tomography.
      Computed imaging has the potential to solve these long-standing limitations.
      Interferometric synthetic aperture microscopy (ISAM)7-9 is a computed imaging
      technique enabling high-resolution volumetric tomography with spatially invariant
      resolution. However, its potential for clinical diagnostics remains largely
      untapped since full volume reconstructions required lengthy postprocessing, and
      the phase-stability requirements have been difficult to satisfy in vivo. Here we
      demonstrate how 3-D Fourier-domain resampling, in combination with high-speed
      optical coherence tomography (OCT), can achieve high-resolution in vivo
      tomography. Enhanced depth sensitivity was achieved over a depth-of-field
      extended in real time by more than an order of magnitude. This work lays the
      foundation for high-speed volumetric cellular-level tomography.

PMID- 23956791
TI  - Contact Between Adoptive and Birth Families: Perspectives from the Minnesota
      Texas Adoption Research Project.
AB  - A growing number of adoptive families have contact with their children's birth
      relatives. The Minnesota Texas Adoption Research Project is examining
      longitudinally the consequences of variations in contact arrangements for birth
      mothers, adoptive parents, and adopted children in domestic infant adoptions, and
      is studying the dynamics of relationships within these family systems.
      Individuals who had contact were more satisfied with their arrangements than
      those who did not have contact. Satisfaction with contact predicted more optimal
      adjustment among adopted adolescents and emerging adults. Adoption-related
      communication predicted identity development among adopted adolescents and
      emerging adults. Birth mothers who were more satisfied with their contact
      arrangements, regardless of level of contact, had less unresolved grief 12 to 20
      years after placement. Adoptive and birth relatives who engage in contact need
      flexibility, strong interpersonal skills, and commitment to the relationship.
      These skills can be learned, and they can be supported by others, through
      informal, psychoeducational, and therapeutic means.

PMID- 23956789
TI  - MRI-based multiscale model for electromagnetic analysis in the human head with
      implanted DBS.
AB  - Deep brain stimulation (DBS) is an established procedure for the treatment of
      movement and affective disorders. Patients with DBS may benefit from magnetic
      resonance imaging (MRI) to evaluate injuries or comorbidities. However, the MRI
      radio-frequency (RF) energy may cause excessive tissue heating particularly near
      the electrode. This paper studies how the accuracy of numerical modeling of the
      RF field inside a DBS patient varies with spatial resolution and corresponding
      anatomical detail of the volume surrounding the electrodes. A multiscale model
      (MS) was created by an atlas-based segmentation using a 1 mm(3) head model (mRes)
      refined in the basal ganglia by a 200  MU m(2) ex-vivo dataset. Four DBS
      electrodes targeting the left globus pallidus internus were modeled.
      Electromagnetic simulations at 128 MHz showed that the peak of the electric field
      of the MS doubled (18.7 kV/m versus 9.33 kV/m) and shifted 6.4 mm compared to the
      mRes model. Additionally, the MS had a sixfold increase over the mRes model in
      peak-specific absorption rate (SAR of 43.9 kW/kg versus 7 kW/kg). The results
      suggest that submillimetric resolution and improved anatomical detail in the
      model may increase the accuracy of computed electric field and local SAR around
      the tip of the implant. 

PMID- 23956792
TI  - Intermittent exercise in response to cigarette cravings in the context of an
      Internet-based smoking cessation program.
AB  - BACKGROUND: Interventions using sustained aerobic exercise programs to aid
      smoking cessation have resulted in modest, short-term cessation rates comparable
      to conventional cessation methods. No smoking cessation trial to date has
      prescribed intermittent bouts of exercise in response to nicotine cravings.
      OBJECTIVES: This pilot randomized controlled trial examined the feasibility and
      efficacy of an Internet-based smoking cessation program alone (CON) vs. the same
      Internet-based program + intermittent exercise in response to cigarette cravings
      (EX). STUDY POPULATION: Participants (N = 38; mean age = 43.6 [SD = 11.5]; 60.5%
      women) were generally healthy, inactive adult smokers who desired to quit.
      RESULTS: The overall retention rate was 60.5% (n = 23), and no significant
      retention rate differences were found between groups (EX vs. CON). Although
      retained participants achieved a higher cessation rate (26.1%) than all enrolled
      participants (15.8%), adjusted intent-to-treat and per-protocol binary logistic
      regression analyses revealed no significant cessation rate differences between EX
      and CON groups. Linear regression results indicated that additional days of self
      reported exercise on the study website during the intervention phase predicted
      significantly higher reduction rates among EX group participants, F(2, 16) =
      31.08, p < .001. CONCLUSIONS: Results were mixed with regard to the incremental
      benefit of exercise in the presence of the apparently valuable Internet-based
      smoking cessation program. The results support findings from related research and
      underscore the need for additional investigation into both the mechanisms
      underlying the effect of exercise on cigarette cravings and the challenges of
      poor adherence in the context of exercise-based smoking cessation interventions.

PMID- 23956793
TI  - Net land-atmosphere flows of biogenic carbon related to bioenergy: towards an
      understanding of systemic feedbacks.
AB  - The notion that biomass combustion is carbon neutral vis-a-vis the atmosphere
      because carbon released during biomass combustion is absorbed during plant
      regrowth is inherent in the greenhouse gas accounting rules in many regulations
      and conventions. But this 'carbon neutrality' assumption of bioenergy is an
      oversimplification that can result in major flaws in emission accounting; it may
      even result in policies that increase, instead of reduce, overall greenhouse gas
      emissions. This commentary discusses the systemic feedbacks and ecosystem
      succession/land-use history issues ignored by the carbon neutrality assumption.
      Based on recent literature, three cases are elaborated which show that the C
      balance of bioenergy may range from highly beneficial to strongly detrimental,
      depending on the plants grown, the land used (including its land-use history) as
      well as the fossil energy replaced. The article concludes by proposing the
      concept of GHG cost curves of bioenergy as a means for optimizing the climate
      benefits of bioenergy policies.

PMID- 23956794
TI  - Targeted therapy for squamous cell lung cancer.
AB  - Lung squamous cell carcinoma (SqCC) is the second most common subtype of non
      small-cell lung cancer and leads to 40,000-50,000 deaths per year in the USA.
      Management of non-small-cell lung cancer has dramatically changed over the past
      decade with the introduction of targeted therapeutic agents for genotypically
      selected individuals with lung adenocarcinoma. These agents lead to improved
      outcomes, and it has now become the standard of care to perform routine molecular
      genotyping of lung adenocarcinomas. By contrast, progress in lung SqCC has been
      modest, and there has yet to be a successful demonstration of targeted therapy in
      this disease. Here, we review exciting work from ongoing genomic characterization
      and biomarker validation efforts that have nominated several likely therapeutic
      targets in lung SqCCs. These studies suggest that targeted therapies are likely
      to be successful in the treatment of lung SqCCs and should be further explored in
      both preclinical models and in clinical trials.

PMID- 23956795
TI  - Single-Cell Force Spectroscopy of Als-Mediated Fungal Adhesion.
AB  - Macroscopic assays that are traditionally used to investigate the adhesion
      behaviour of microbial cells provide averaged information obtained on large
      populations of cells and do not measure the fundamental forces driving single
      cell adhesion. Here, we use single-cell force spectroscopy (SCFS) to quantify the
      specific and non-specific forces engaged in the adhesion of the human fungal
      pathogen Candida albicans. Saccharomyces cerevisiae cells expressing the C.
      albicans adhesion protein Als5p were attached on atomic force microscopy tipless
      cantilevers using a bioinspired polydopamine wet polymer, and force-distance
      curves were recorded between the obtained cell probes and various solid surfaces.
      Force signatures obtained on hydrophobic substrates exhibited large adhesion
      forces (1.25 +/- 0.2 nN) with extended rupture lengths (up to 400 nm), attributed
      to the binding and stretching of the hydrophobic tandem repeats of Als5p. Data
      collected on fibronectin (Fn) -coated substrates featured strong adhesion forces
      (2.8 +/- 0.6 nN), reflecting specific binding between Fn and the N-terminal
      immunoglobulin-like regions of Als5p, followed by weakly adhesive macromolecular
      bonds. Both hydrophobic and Fn adhesion forces increased with contact time,
      emphasizing the important role that time plays in strengthening adhesion. Our
      SCFS methodology provides a versatile platform in biomedicine for understanding
      the fundamental forces driving adhesion and biofilm formation in fungal
      pathogens.

PMID- 23956796
TI  - ENDOCYTOSIS PATHWAYS FOR NUCLEIC ACID THERAPEUTICS.
AB  - The development of nanoscale delivery vehicles for siRNAs is a current topic of
      considerable importance. However, little is understood about the exact
      trafficking mechanisms for siRNA-vehicle complexes across the plasma membrane and
      into the cytoplasm. While some information can be gleaned from studies on
      delivery of plasmid DNA, the different delivery requirements for these two
      vehicles makes drawing specific conclusions a challenge. However, using chemical
      inhibitors of different endocytosis pathways, studies on which endocytotic
      pathways are advantageous and deleterious for the delivery of nucleic acid drugs
      are emerging. Using this information as a guide, it is expected that the future
      development of effective siRNA delivery vehicles and therapeutics will be greatly
      improved.

PMID- 23956797
TI  - Using balance training to improve the performance of youth basketball players.
AB  - The aim of this study was to evaluate the effectiveness of 12 weeks of balance
      training to improve the balance and vertical jump abilities of young basketball
      players. Twenty-three players from two teams in the Under Fifteen Basketball
      Excellence category participated in the study. Participants were divided into two
      training groups: balance training (BAL, n = 11) and isotonic training (ISO, n =
      12). Both groups were tested for balance and vertical jumps at the beginning of
      the competitive season and at the end of 12 weeks of specific training programme.
      All of the tests were performed in sustained bipodalic and monopodalic (both
      right and left) positions. The results showed that players who participated in
      balance training for 12 weeks, compared to players who trained with isotonic
      machines, exhibited a significantly increase in balance (bipodalic 28.3 %; right
      41.4 %; left 45.8 %; p < 0.01) and muscular power (bipodalic 8.1 %; right 13.5 %;
      left 12.5 %; p < 0.01) as measured through a vertical jump. In conclusion,
      balance training using unstable boards was an effective training method for
      improving balance and the vertical jump, which is a basketball-specific action
      that frequently occurs in this sport.

PMID- 23956798
TI  - Detection of Steps in Single Molecule Data.
AB  - Over the past few decades, single molecule investigations employing optical
      tweezers, AFM and TIRF microscopy have revealed that molecular behaviors are
      typically characterized by discrete steps or events that follow changes in
      protein conformation. These events, that manifest as steps or jumps, are short
      lived transitions between otherwise more stable molecular states. A major
      limiting factor in determining the size and timing of the steps is the noise
      introduced by the measurement system. To address this impediment to the analysis
      of single molecule behaviors, step detection algorithms incorporate large records
      of data and provide objective analysis. However, existing algorithms are mostly
      based on heuristics that are not reliable and lack objectivity. Most of these
      step detection methods require the user to supply parameters that inform the
      search for steps. They work well, only when the signal to noise ratio (SNR) is
      high and stepping speed is low. In this report, we have developed a novel step
      detection method that performs an objective analysis on the data without input
      parameters, and based only on the noise statistics. The noise levels and
      characteristics can be estimated from the data providing reliable results for
      much smaller SNR and higher stepping speeds. An iterative learning process drives
      the optimization of step-size distributions for data that has unimodal step-size
      distribution, and produces extremely low false positive outcomes and high
      accuracy in finding true steps. Our novel methodology, also uniquely incorporates
      compensation for the smoothing affects of probe dynamics. A mechanical
      measurement probe typically takes a finite time to respond to step changes, and
      when steps occur faster than the probe response time, the sharp step transitions
      are smoothed out and can obscure the step events. To address probe dynamics we
      accept a model for the dynamic behavior of the probe and invert it to reveal the
      steps. No other existing method addresses the impact of probe dynamics on step
      detection. Importantly, we have also developed a comprehensive set of tools to
      evaluate various existing step detection techniques. We quantify the performance
      and limitations of various step detection methods using novel evaluation scales.
      We show that under these scales, our method provides much better overall
      performance. The method is validated on different simulated test cases, as well
      as experimental data.

PMID- 23956799
TI  - Shear Stress Activates eNOS at the Endothelial Apical Surface Through beta1
      Containing Integrins and Caveolae.
AB  - There is now a large body of evidence demonstrating that fluid mechanical forces
      generated by blood flowing through the vasculature play a direct role in
      regulating endothelial cell structure and function. Integrin receptors that
      localize to the basal surface of the endothelium participate in both outside-in
      and inside-out signaling events that influence endothelial gene expression and
      morphology in response to flow. Our analyses of apical plasma membranes derived
      from cultured bovine aortic endothelial cells revealed that integrins are also
      expressed on this cell surface. Here, we tested whether these integrins
      participate in mechanotransduction events that are known to occur on the
      endothelial cell luminal/apical membrane. We found that apically expressed beta1
      integrins are rapidly activated in response to acute shear stress. Blockade of
      beta1 integrin activation attenuated a shear-induced signaling cascade involving
      Src-family kinase, PI3-kinase, Akt and eNOS on this cell surface. In addition,
      beta1 integrin activation and associated signaling events were dependent on the
      structural integrity of caveolae but not the actin cytoskeleton. Taken together,
      these data indicate that endothelial responses to shear stress are mediated by
      spatially distinct pools of integrins.

PMID- 23956800
TI  - Electrocatalytic Reduction of Carbon Dioxide to Carbon Monoxide by a Polymerized
      Film of an Alkynyl-Substituted Rhenium(I) Complex.
AB  - The alkynyl-substituted ReI complex [Re(5,5'-bisphenylethynyl-2,2'
      bipyridyl)(CO)3Cl] was immobilized by electropolymerization onto a Pt-plate
      electrode. The polymerized film exhibited electrocatalytic activity for the
      reduction of CO2 to CO. Cyclic voltammetry studies and bulk controlled-potential
      electrolysis experiments were performed by using a CO2-saturated acetonitrile
      solution. The CO2 reduction, determined by cyclic voltammetry, occurs at
      approximately -1150 mV versus the normal hydrogen electrode (NHE). Quantitative
      analysis by GC and IR spectroscopy was used to determine a Faradaic efficiency of
      approximately 33 % for the formation of CO. Both values of the modified electrode
      were compared to the performance of the homogenous monomer [Re(5,5'
      bisphenylethynyl-2,2'-bipyridyl)(CO)3Cl] in acetonitrile. The polymer formation
      and its properties were studied by using SEM, AFM, and attenuated total
      reflectance (ATR) FTIR and UV/Vis spectroscopy.

PMID- 23956801
TI  - Chemically Advanced Template Search (CATS) for Scaffold-Hopping and Prospective
      Target Prediction for 'Orphan' Molecules.

PMID- 23956802
TI  - Probing the Selectivity of Monoamine Transporter Substrates by Means of Molecular
      Modeling.

PMID- 23956803
TI  - Classification of High-Activity Tiagabine Analogs by Binary QSAR Modeling.

PMID- 23956804
TI  - How Far Could We Go with Open Data - A Case Study for TRPV1 Antagonists.
AB  - Publicly open databases of small compounds have become an indispensable tool for
      chemoinformaticians for collection and preparation of datasets suitable for drug
      discovery questions. Since these databases comprise compounds coming from
      structure-activity relationship (SAR) studies performed by different research
      groups, they are very diverse with respect to the biological assays used. In the
      present study we analyzed the applicability of a thoroughly curated dataset
      gathered from open sources for ligand-based studies, using the transient receptor
      potential vanilloid type 1 (TRPV1) as use case. Thorough curation of compounds
      according to the biological assay type and conditions led to a dataset of
      comparable bioactive chemicals. Subsequent exhaustive analysis of the obtained
      dataset using classification algorithms demonstrated that the models obtained in
      most of the cases possess reliable quality. Analysis of constantly misclassified
      compounds showed that they belong to local SAR series, where small changes in
      structure lead to different class labels. These small structural differences
      could not be captured by the classification algorithms. However application of
      the 3D alignment-independent QSAR technique GRIND for local, structurally related
      series overcomes this problem.

PMID- 23956805
TI  - Acute splenic irradiation reduces brain injury in the rat focal ischemic stroke
      model.
AB  - Removing the spleen prior to ischemic stroke abrogates immunologic response to
      brain injury and reduces cerebral infarction. However, the effectiveness of
      splenectomy for neuroprotection after stroke has not been established. Moreover,
      the risks of the surgical splenectomy in stroke patients create a major obstacle
      to removing the spleen's inflammatory response. We hypothesized that acute
      splenic irradiation will ablate splenic cells and thereby will diminish stroke
      progression. Male adult Sprague Dawley rats were subjected to 2-hour middle
      cerebral artery occlusion (MCAO), then CT scanned for spleen localization and
      irradiated to the lateral splenic region with 8Gy of Cobalt 60 at 3, 4, 6 or 8
      hrs after start of cerebral ischemia. Untreated controls underwent the same
      procedures except that sham irradiation was applied. At 2 or 7 days after
      ischemia the rats were euthanized, and brains recovered for the assessment of
      brain injury and the extent of neuroinflammation. Irradiation at 3 hrs reduced
      spleen weight and lymphocyte blood levels after stroke. Splenic irradiation at 3
      and 4 hrs after start of ischemia significantly reduced cerebral infarction
      volumes measured at 48 hrs and 7 days, respectively. The histological analysis on
      day 7 revealed reduced counts of microglia, infiltrating T cells, and apoptotic
      neurons in the rats irradiated at 4 hrs. The noninvasive single-dose procedure of
      splenic irradiation performed within a time interval of up to 4 hours offers
      neuroprotection against ischemic stroke possibly by abrogating deployment of
      splenic cells to the brain. 

PMID- 23956806
TI  - The Implementation of Mindfulness-Based Cognitive Therapy: Learning From the UK
      Health Service Experience.
AB  - Mindfulness-based cognitive therapy (MBCT) is an effective depression prevention
      programme for people with a history of recurrent depression. In the UK, the
      National Institute for Clinical Excellence (NICE) has suggested that MBCT is a
      priority for implementation. This paper explores the exchange, synthesis and
      application of evidence and guidance on MBCT between the academic settings
      generating the evidence and delivering practitioner training and the practice
      settings where implementation takes place. Fifty-seven participants in a workshop
      on MBCT implementation in the NHS were asked for their experience of facilitators
      and obstacles to implementation, and a UK-wide online survey of 103 MBCT teachers
      and stakeholders was conducted. While MBCT is starting to become available in the
      NHS, this is rarely part of a strategic, coherent or appropriately resourced
      approach. A series of structural, political cultural, educational, emotional and
      physical/technological obstacles and facilitators to implementation were
      identified. Nearly a decade since NICE first recommended MBCT, only a small
      number of mental health services in the UK have systematically implemented the
      guidance. Guiding principles for implementation are set out. We offer an
      implementation resource to facilitate the transfer of MBCT knowledge into action.

PMID- 23956807
TI  - Intra-crystalline protein diagenesis (IcPD) in Patella vulgata. Part I: Isolation
      and testing of the closed system.
AB  - This study successfully isolates a fraction of intra-crystalline proteins from
      shells of the marine gastropod Patella vulgata and assesses the suitability of
      these proteins for IcPD (Intra-crystalline Protein Diagenesis) geochronology. We
      discuss the mineralogical composition of this gastropod, investigated for the
      first time by X-ray diffraction mapping, and use the results to inform our
      sampling strategy. The potential of the calcitic rim and of a bulk sample
      (containing both apex and rim) of the shell to act as stable repositories for the
      intra-crystalline proteins during diagenesis is examined. The composition and the
      diagenetic behaviour of the intra-crystalline proteins isolated from different
      locations within the shell are compared, highlighting the necessity of targeting
      consistent sampling positions. We induced artificial diagenesis of both intra
      crystalline and whole-shell proteins by conducting high-temperature experiments
      in hydrous environment; this allowed us to quantify the loss of amino acids by
      leaching and therefore evaluate the open- or closed-system behaviour of the
      different fractions of proteins. The results obtained provide further
      confirmation that patterns of diagenesis vary according to the protein sequence,
      structure, and location within or outside the intra-crystalline fraction. As
      Patella is frequently found in the fossil record, both in archaeological and
      geological contexts, the application of IcPD geochronology to this biomineral
      opens up the possibility to obtain reliable age information from a range of sites
      in different areas of the world.

PMID- 23956808
TI  - Intra-crystalline protein diagenesis (IcPD) in Patella vulgata. Part II:
      Breakdown and temperature sensitivity.
AB  - Artificial diagenesis of the intra-crystalline proteins isolated from Patella
      vulgata was induced by isothermal heating at 140  degrees C, 110  degrees C and
      80  degrees C. Protein breakdown was quantified for multiple amino acids,
      measuring the extent of peptide bond hydrolysis, amino acid racemisation and
      decomposition. The patterns of diagenesis are complex; therefore the kinetic
      parameters of the main reactions were estimated by two different methods: 1) a
      well-established approach based on fitting mathematical expressions to the
      experimental data, e.g. first-order rate equations for hydrolysis and power
      transformed first-order rate equations for racemisation; and 2) an alternative
      model-free approach, which was developed by estimating a "scaling" factor for the
      independent variable (time) which produces the best alignment of the experimental
      data. This method allows the calculation of the relative reaction rates for the
      different temperatures of isothermal heating. High-temperature data were compared
      with the extent of degradation detected in sub-fossil Patella specimens of known
      age, and we evaluated the ability of kinetic experiments to mimic diagenesis at
      burial temperature. The results highlighted a difference between patterns of
      degradation at low and high temperature and therefore we recommend caution for
      the extrapolation of protein breakdown rates to low burial temperatures for
      geochronological purposes when relying solely on kinetic data.

PMID- 23956810
TI  - Artefacts and Family Resemblance.
AB  - I develop in this paper a conception of artefacts based on L. Wittgenstein's idea
      of family resemblance. My approach peruses the notion of frame, which was
      invented in cognitive psychology as an operationisable extension of this
      philosophical idea. Following the metaphor of life-cycle I show how this
      schematic notion of frame may be filled with the content relevant for artefacts
      if we consider them from the point of view of their histories. The resulting
      conception of artefacts provides a new insight into the current debate on
      artefact categorisation.

PMID- 23956809
TI  - Spatiotemporal patterns of infant bronchiolitis in a Tennessee  Medicaid
      population.
AB  - Respiratory syncytial virus (RSV) is a major cause of worldwide morbidity and
      mortality in infants, primarily through the induction of bronchiolitis. RSV
      epidemics are highly seasonal, occurring in the winter months in the northern
      hemisphere. Within the United States, RSV epidemic dynamics vary both spatially
      and temporally. This analysis employs a retrospective space-time scan statistic
      to locate spatiotemporal clustering of infant bronchiolitis in a very large
      Tennessee (TN) Medicaid cohort. We studied infants less than 6 months of age (N =
      52,468 infants) who had an outpatient visit, emergency department visit, or
      hospitalization for bronchiolitis between 1995 and 2008. The scan statistic
      revealed distinctive and consistent patterns of deviation in epidemic timing.
      Eastern TN (Knoxville area) showed clustering in January and February, and
      Central TN (Nashville area) in November and December. This is likely due to local
      variation in geography-associated factors which should be taken into
      consideration in future modeling of RSV epidemics.

PMID- 23956811
TI  - Bayesian Dose Finding for Combined Drugs with Discrete and Continuous Doses.
AB  - The trend of treating patients with combined drugs has grown in cancer clinical
      trials. Often, evaluating the synergism of multiple drugs is the primary
      motivation for such drug-combination studies. To enhance the patient response, a
      new cancer therapeutic agent is often investigated together with an existing
      standard of care (SOC) agent. At least a certain amount of dosage of the SOC is
      administered in order to maintain some therapeutic effects in patients. For
      clinical trials involving a continuous-dose SOC and a discrete-dose agent, we
      propose a two-stage Bayesian adaptive dose-finding design. The first stage takes
      a continual reassessment method to locate the appropriate dose for the discrete
      dose agent while fixing the continuous-dose SOC at the minimal therapeutic dose.
      In the second stage, we make a fine dose adjustment by calibrating the continuous
      dose to achieve the target toxicity rate as closely as possible. Dose escalation
      or de-escalation is based on the posterior estimates of the joint toxicity
      probabilities of combined doses. As the toxicity data accumulate during the
      trial, we adaptively assign each cohort of patients to the most appropriate dose
      combination. We conduct extensive simulation studies to examine the operating
      characteristics of the proposed two-stage design and demonstrate the design's
      good performance with practical scenarios.

PMID- 23956812
TI  - QTL clustering as a mechanism for rapid multi-trait evolution.
AB  - Cave-dwelling animals exhibit remarkable convergence in multiple cave-related
      traits, yet the genetic mechanisms responsible for the evolution and integration
      of many such traits remain unclear. Astyanax mexicanus is a model cave-dwelling
      fish with sighted surface-dwelling (surface fish) and blind cave-dwelling
      (cavefish) forms. Using a genetic cross between these morphs, we discovered
      significant correlations among several cave-related traits, including reduced
      eyes, increased superficial neuromast receptors located within the eye orbit (EO
      SN) and a vibration-attraction behavior (VAB) that facilitates foraging in
      darkness. Furthermore, we discovered that the quantitative trait loci (QTL)
      underlying these traits are clustered within the Astyanax genome. Following an
      ablation experiment that demonstrated that the EO SN contribute to VAB, we
      concluded that the adaptive evolution of VAB and EO SN has likely contributed to
      eye loss in cavefish. In this addendum, we further discuss the possible role of
      multi-trait QTL clustering in facilitating rapid adaptation. 

PMID- 23956813
TI  - Cell coordination of collective migration by Rab11 and Moesin.
AB  - Cell migration is an important process involved in developmental events and in
      pathologies such as cancer. Cell migration can be classified into two types:
      individual and collective cell movements. Compared with individual migration,
      collective cell migration is less understood and has drawn increasing attention
      lately because of its emerging role in cancer spreading. We have recently
      established that Rab11 is absolutely required for spatial control of Rac1
      activity through the control of cell-cell communication during collective
      movements (Ramel, et al. 2013). Moreover, we demonstrated that Rab11 acts through
      the control of Moesin activity. Here, we discuss how Rab11 and Moesin could
      cooperate to transfer forces from cell to cell in order to insure coordinated
      collective cell migration. 

PMID- 23956814
TI  - Roles of mitochondrial dynamics under stressful and normal conditions in yeast
      cells.
AB  - Eukaryotic cells contain dynamic mitochondrial filaments: they fuse and divide.
      Here we summarize data on the protein machinery driving mitochondrial dynamics in
      yeast and also discuss the factors that affect the fusion-fission balance.
      Fission is a general stress response of cells, and in the case of yeast this
      response appears to be prosurvival. At the same time, even under normal
      conditions yeast mitochondria undergo continuous cycles of fusion and fission.
      This seems to be a futile cycle and also expensive from the energy point of view.
      Why does it exist? Benefits might be the same as in the case of sexual
      reproduction. Indeed, mixing and separating of mitochondrial content allows
      mitochondrial DNA to segregate and recombine randomly, leading to high variation
      in the numbers of mutations per individual mitochondrion. This opens a
      possibility for effective purifying selection-elimination of mitochondria highly
      contaminated by deleterious mutations. The beneficial action presumes a mechanism
      for removal of defective mitochondria. We argue that selective mitochondrial
      autophagy or asymmetrical distribution of mitochondria during cell division could
      be at the core of such mechanism.

PMID- 23956815
TI  - Tamoxifen vs Raloxifene vs Exemestane for Chemoprevention.
AB  - Clinical trial data on selective estrogen receptor modulators (SERMs) and
      aromatase inhibitors (AIs) have demonstrated reduced breast cancer incidence in
      the prevention setting among high-risk women. We conducted an extensive review of
      clinical trials and recent published reports of barriers to uptake of breast
      cancer chemoprevention, to provide health care professionals with information to
      improve decision-making regarding chemoprevention. Despite the positive results
      of these trials, uptake of chemoprevention has been low due to barriers in
      identifying high-risk women, lack of understanding of risks and benefits, as well
      as concerns about side effects. Interventions designed to increase uptake have
      met with limited success. Clinicians can support women in informed decision
      making about SERMs and AIs by effectively communicating breast cancer risk and
      enhancing knowledge about the risks and benefits of chemoprevention. Promoting
      uptake and adherence to chemoprevention holds promise for reducing the public
      health burden of this disease.

PMID- 23956816
TI  - Synthesis and Metabolic Studies of Host Directed Inhibitors for Anti Viral
      Therapy.
AB  - Targeting host cell factors required for virus replication provides an
      alternative to targeting pathogen components and represents a promising approach
      to develop broad-spectrum antiviral therapeutics. High-throughput screening (HTS)
      identified two classes of inhibitors (2 and 3) with broad-spectrum antiviral
      activity against ortho- and paramyxoviruses including influenza A virus (IAV),
      measles virus (MeV), respiratory syncytial virus (RSV), and human parainfluenza
      virus type 3 (HPIV3). Hit-to-lead optimization delivered inhibitor, 28a, with
      EC50 values of 0.88 and 0.81 MUM against IAV strain WSN and MeV strain Edmonston,
      respectively. It was also found that compound 28a delivers good stability in
      human liver S9 fractions with a half-life of 165 minutes. These data establish
      28a as a promising lead for antiviral therapy through a host-directed mechanism.

PMID- 23956817
TI  - Quantum Beats and Coherence Decay in Degenerate States Split by Solvation.
AB  - Coherent dynamics of degenerate quantum states symmetry-broken on the femtosecond
      timescale is found to exhibit the phenomenon of quantum beats. Frequency-resolved
      and polarization-selective heterodyned transient grating spectroscopy enabled us
      to retrieve the oscillation pattern characteristic of the beating in systems
      undergoing ultrafast dynamical processes. This methodology applies to the general
      phenomena of coherence dynamics which is important in any ultrafast
      multidimensional spectroscopy. A particular application to the vibrational
      spectroscopy of coherence in the degenerate normal modes of the tricyanomethanide
      anion solvated in water is explored in this study. The relaxation of the cross
      polarization transient grating anisotropy is shown to reflect the loss of the
      vibrational coherence, which is caused by ultrafast dynamics of the water
      solvation shell.

PMID- 23956818
TI  - Two-Dimensional Infrared (2DIR) Spectroscopy of the Peptide Beta3s Folding.
AB  - Probing underlying free energy landscape, pathways, and mechanism is the key for
      understanding protein folding in theory and experiment. Recently time-resolved
      two-dimensional infrared (2DIR) with femtosecond laser pulses, has emerged as a
      promising tool for investigating the protein folding dynamics on faster
      timescales than possible by NMR. We have employed molecular dynamics simulations
      to compute 2DIR spectra of the folding process of a peptide, Beta3s. Simulated
      non-chiral and chiral 2DIR signals illustrate the variation of the spectra as the
      peptide conformation evolves along the free energy landscape. Chiral spectra show
      stronger changes than the non-chiral signals because cross peaks caused by the
      formation of the beta-sheet are clearly resolved. Chirality-induced 2DIR may be
      used to detect the folding of beta-sheet proteins with high spectral and temporal
      resolution.

PMID- 23956819
TI  - Intracellular 'wiring' for real-time cell communication.

PMID- 23956820
TI  - Trauma, mental health, and intergenerational associations in Kosovar Families 11
      years after the war.
AB  - BACKGROUND: While there is a considerable amount of literature addressing
      consequences of trauma in veterans and holocaust survivors, war and postwar
      civilian populations, particularly children, are still understudied. Evidence
      regarding intergenerational effects of trauma in families is inconsistent.
      OBJECTIVE: To shed light on intergenerational aspects of trauma-related mental
      health problems among families 11 years after the Kosovo war. METHOD: In a cross
      sectional study, a paired sample of 51 randomly selected triplets (school-aged
      child, mother, father, N=153) of Kosovar families was investigated with regard to
      trauma exposure, posttraumatic stress (UCLA Posttraumatic Diagnostic Scale),
      anxiety (Spence Children's Anxiety Scale, Hopkins Symptom Checklist-25), and
      depressive symptoms (Depressionsinventar fur Kinder und Jugendliche [DIKJ;
      depression inventory for children and adolescents], Hopkins Symptom Checklist
      25). RESULTS: Considerable trauma exposure and high prevalence rates of
      clinically relevant posttraumatic stress, anxiety, and depressive symptoms were
      found in both parents and children. While strong correlations were found between
      children's depressive symptoms and paternal posttraumatic stress, anxiety and
      depressive symptoms, maternal symptoms did not correlate with their children's.
      In multiple regression analyses, only posttraumatic stress symptoms of fathers
      were significantly related with children's depressive symptoms. CONCLUSION:
      Eleven years after the Kosovo war, the presence of posttraumatic stress, anxiety,
      and depressive symptoms in civilian adults and their children is still
      substantial. As symptoms of parents and children are associated, mental health
      problems of close ones should be actively screened and accounted for in
      comprehensive treatment plans, using a systemic approach. Future research should
      include longitudinal studies conducting multivariate analyses with larger sample
      sizes in order to investigate indicators, causal and resilience factors.

PMID- 23956821
TI  - The era of robotic and minimally invasive surgery.

PMID- 23956822
TI  - Current evaluation and treatment of nocturia.
AB  - Nocturia is usually considered to be just one of the symptoms included with lower
      urinary tract symptoms (LUTS) and is treated with therapy based on LUTS. Recent
      research suggests, however, that nocturia is not merely a simple symptom of LUTS
      but is a multifactorial condition with many contributing etiological factors. The
      causes of nocturia can be classified into bladder storage problems, increased
      urine output, sleep disturbance problems, and other potential diseases. The
      frequency-volume chart (FVC) is very important in evaluating and diagnosing
      nocturia. Patients usually record the volume and timing of voids for a period of
      1 to 3 days on the FVC. The FVC data can provide information on voiding patterns
      and clues about the etiology and treatment of nocturia. It is doubtful that alpha
      blockers will have clinical significance for treatment because the difference in
      nocturia episodes between treatment with alpha-blockers and placebo is too small.
      Antimuscarinics also exert no effect on nocturnal polyuria, and the evidence
      supporting the efficacy of antimuscarinics for the treatment of nocturia is
      limited. However, several randomized placebo-controlled trials have shown the
      efficacy of oral desmopressin in the treatment of adults with nocturia. Short
      acting hypnotics may be helpful for patients with sleep disturbances. Although
      surgical or interventional therapy is not indicated for nocturia, transurethral
      resection of the prostate appears to confer a greater improvement in benign
      prostatic hyperplasia symptoms including nocturia. The management of nocturia may
      require a team approach by making optimal use of multidisciplinary expertise. 

PMID- 23956823
TI  - Effect of type 2 diabetes mellitus on prognosis of nonmetastatic renal cell
      cancer.
AB  - PURPOSE: We evaluated the prognostic value of type 2 diabetes mellitus (DM) in
      patients treated surgically for localized renal cell carcinoma (RCC). MATERIALS
      AND METHODS: Between 1995 and 2011, 588 patients with renal tumor diagnoses were
      treated surgically and 492 patients with pathologically confirmed nonmetastatic
      RCC diagnoses were included in the study. The associations of clinical and
      pathologic parameters with a type 2 DM diagnosis were evaluated. Kaplan-Meier
      estimations for disease-specific survival (DSS) and overall survival (OS) were
      generated according to type 2 DM diagnosis, and the log-rank test was used to
      compare survival according to the variables. RESULTS: The mean age of the
      patients was 56.7+/-12 years (range, 15 to 84 years; median, 58 years) and the
      mean length of follow-up was 35.9+/-28 months (range, 1 to 145 months; median,
      34.3 months). Of the 492 patients, 62 (12.6%) had a diagnosis of DM at the time
      of surgery (group I) and 430 did not have DM (group II). The mean age and the
      incidence of clear cell RCC histological subtype were significantly higher in
      group I than in group II (p<0.001 and p=0.036, respectively). Although DSS and OS
      were lower in group I, this difference was not significant. Type 2 DM was not
      detected as an independent prognostic factor for DSS and OS. CONCLUSIONS: This
      study investigated the role and effect of DM on the prognosis of localized RCC
      that was treated surgically. The present study did not detect DM as an
      independent prognostic factor for RCC.

PMID- 23956824
TI  - Usefulness of the ice-cream cone pattern in computed tomography for prediction of
      angiomyolipoma in patients with a small renal mass.
AB  - PURPOSE: A morphologic contour method for assessing an exophytic renal mass as
      benign versus malignant on the basis of the shape of the interface with the renal
      parenchyma was recently developed. We investigated the usefulness of this
      morphologic contour method for predicting angiomyolipoma (AML) in patients who
      underwent partial nephrectomy for small renal masses (SRMs). MATERIALS AND
      METHODS: From January 2004 to March 2013, among 197 patients who underwent
      partial nephrectomy for suspicious renal cell carcinoma (RCC), the medical
      records of 153 patients with tumors (AML or RCC) <=3 cm in diameter were
      retrospectively reviewed. Patient characteristics including age, gender, type of
      surgery, size and location of tumor, pathologic results, and specific findings of
      the imaging study ("ice-cream cone" shape) were compared between the AML and RCC
      groups. RESULTS: AML was diagnosed in 18 patients and RCC was diagnosed in 135
      patients. Gender (p=0.001), tumor size (p=0.032), and presence of the ice-cream
      cone shape (p=0.001) showed statistically significant differences between the AML
      group and the RCC group. In the multivariate logistic regression analysis, female
      gender (odds ratio [OR], 5.20; 95% confidence interval [CI], 1.45 to 18.57;
      p=0.011), tumor size (OR, 0.34; 95% CI, 0.12 to 0.92; p=0.034), and presence of
      the ice-cream cone shape (OR, 18.12; 95% CI, 4.97 to 66.06; p=0.001) were
      predictors of AML. CONCLUSIONS: This study confirmed a high incidence of AML in
      females. Also, the ice-cream cone shape and small tumor size were significant
      predictors of AML in SRMs. These finding could be beneficial for counseling
      patients with SRMs.

PMID- 23956825
TI  - Do positive surgical margins predict biochemical recurrence in all patients
      without adjuvant therapy after radical prostatectomy?
AB  - PURPOSE: The objective was to study whether positive surgical margins (PSMs)
      predict biochemical recurrence (BCR) in all patients without adjuvant therapy
      after radical prostatectomy (RP). MATERIALS AND METHODS: We retrospectively
      reviewed the medical records of patients who underwent RP for prostate cancer at
      Veterans Health Service Medical Center from 2005 to 2011. BCR was defined by a
      prostate-specific antigen (PSA) value >=0.2 ng/mL. The clinicopathological
      factors of the PSM group were compared with those of the negative surgical margin
      (NSM) group, and the predictive impact of a PSM for BCR-free survival were
      evaluated. In addition, we analyzed the prognostic difference for BCR-free
      survival between solitary and multiple PSMs. RESULTS: A PSM was noted in 167
      patients (45.5%). BCR was reported in 101 men in total (27.5%). The BCR-free
      survival rate of the PSM group was lower than that of the NSM group (p<0.001). In
      a multivariate analysis for the total patients, PSM was significantly associated
      with BCR-free survival (p<0.001). After stratification by pathological T stage,
      Gleason score (GS), and preoperative PSA value, PSM was significantly predictive
      for BCR-free survival in men with pT2 and/or GS <=6 or 7 and/or a PSA value <10
      or 10-20 ng/mL (all p<0.05). Multiple PSMs were more predictive of BCR-free
      survival than was a solitary PSM (p=0.001). CONCLUSIONS: A PSM is a significant
      predictor of postoperative BCR in patients with pT2 and/or GS <=7 and/or
      preoperative PSA <20 ng/mL. Multiple PSMs are considered a stronger prognostic
      factor for prediction of BCR than is a solitary PSM.

PMID- 23956826
TI  - Single-surgeon experience with robot-assisted ureteroneocystostomy for distal
      ureteral pathologies in adults.
AB  - PURPOSE: To demonstrate our technical approach for robot-assisted
      ureteroneocystostomy (R-UNC) for benign and malignant distal ureteral
      pathologies. MATERIALS AND METHODS: Between January 2009 and January 2013, a
      total of 10 patients underwent R-UNC in the distal ureter by a single surgeon.
      Indications for R-UNC were as follows: idiopathic (3), fistula (2), iatrogenic
      (2), malignancy (2), and chronic vesicoureteral reflux (1). RESULTS: Tension-free
      anastomosis was attained in all 10 R-UNC procedures. A psoas hitch was performed
      in 6/10 cases (60%). Intravesical and extravesical reimplantations were completed
      in 5/10 (50%) and 5/10 cases (50%), respectively. A nonrefluxing ureter was
      constructed in 2/10 cases (20%). The patients' mean age was 52.9+/-16.6 years,
      their mean body mass index was 30.8+/-6.3 kg/m(2), the mean operative time was
      211.7+/-69.3 minutes, mean estimated blood loss was 102.5+/-110.8 mL, and mean
      length of stay was 2.8+/-2.3 days. There were no intraoperative complications.
      There was one Clavien-Dindo grade I and one Clavien-Dindo grade II postoperative
      complication. The mean postoperative follow-up duration was 28.5+/-15.5 months.
      Two patients had recurrence of ureteral strictures at 3 months postoperatively
      and were managed successfully with balloon dilation. CONCLUSIONS: Our technique
      for R-UNC demonstrates good perioperative outcomes. However, underlying
      periureteral inflammation and pelvic adhesions may predispose patients for
      stricture recurrence after R-UNC.

PMID- 23956827
TI  - Experience with robot-assisted laparoscopic radical prostatectomy at a secondary
      training hospital: operation time, treatment outcomes, and complications with the
      accumulation of experience.
AB  - PURPOSE: To investigate the learning curve and outcomes of robot-assisted
      laparoscopic radical prostatectomy (RALP) performed by a relatively lower volume
      surgeon at a secondary training hospital. MATERIALS AND METHODS: The medical
      records and the surgery video recordings of 100 patients who underwent RALP by a
      single surgeon between March 2010 and January 2013 were reviewed. The first 10
      cases were grouped into period 1, cases 11 to 40 into period 2, cases 41 to 70
      into period 3, and cases 71 to 100 into period 4. The interval between the
      operations, the operative time for each step of the surgery, the total console
      time, and the operative outcomes were investigated. RESULTS: The mean interval
      between surgeries was 10.6+/-9.3 days. The console time decreased progressively
      after the first 10 cases and reached under 3 hours after 75 cases. The time taken
      to begin dissection of the dorsal vein complex, for the division of the bladder
      neck, for lateral dissection with neurovascular bundle preservation, and for apex
      dissection decreased significantly with experience, although the time for
      vesicourethral anastomosis did not. The margin-positive rate of stage T2 patients
      was 27.4% (20/73), and the transfusion rate was 50% in period 1 patients and 3.3%
      in period 4 patients. No major complications occurred. CONCLUSIONS: It is
      difficult to shorten the learning curve of surgeons in secondary training
      hospitals owing to the smaller number of cases and the irregular surgical
      intervals. Although the operation time was relatively longer, the surgical
      outcome and complication rates were comparable with those of surgeons at larger
      hospitals.

PMID- 23956828
TI  - A prospective randomized controlled trial of the efficacy of tamsulosin after
      extracorporeal shock wave lithotripsy for a single proximal ureteral stone.
AB  - PURPOSE: The objective of this study was to evaluate the efficacy of tamsulosin
      on stone clearance after extracorporeal shock wave lithotripsy (ESWL) in patients
      with a single proximal ureteral stone. MATERIALS AND METHODS: This prospective
      randomized controlled trial was performed on 88 patients with a single proximal
      ureteral stone. After consenting with a doctor, the patients were allocated to
      the treatment (tamsulosin 0.2 mg once a day) or control (no medication) group,
      and the efficacy of tamsulosin was evaluated. The primary outcome of this study
      was the stone-free rate, and the secondary outcomes were the period until
      clearance, pain intensity, analgesic requirement, and incidence of complications.
      RESULTS: A stone-free state was reported in 37 patients (84.1%) in the treatment
      group and 29 (65.9%) in the control group (p=0.049). The mean expulsion period of
      the stone fragments was 10.0 days in the treatment group and 13.2 days in the
      control group (p=0.012). There were no statistically significant differences in
      aceclofenac requirement or pain score between the two groups. Only one patient in
      the treatment group experienced transient dizziness associated with medical
      expulsive therapy, and this adverse event disappeared spontaneously. CONCLUSIONS:
      The results of this prospective randomized controlled trial of the efficacy of
      tamsulosin after ESWL for a single proximal ureteral stone suggest that
      tamsulosin helps in the earlier clearance of stone fragments and reduces the
      expulsion period of stone fragments after ESWL.

PMID- 23956829
TI  - Relationship Between Patient Position and Pain Severity During Shock Wave
      Lithotripsy for Renal Stones With the MODULITH SLX-F2 Lithotripter: A Matched
      Case-Control Study.
AB  - PURPOSE: We evaluated the association between shock wave lithotripsy (SWL)
      related pain and patient positioning during SWL. MATERIALS AND METHODS: We
      retrospectively reviewed the medical records of 162 patients who underwent their
      first SWL session for single renal stones from May 2010 to August 2011. One
      hundred thirteen patients underwent SWL in the supine position and 49 did so in
      the lateral position. To evaluate an unbiased estimation of the positional effect
      on pain severity during SWL, both groups (supine vs. lateral) were matched
      according to sex, age, body mass index, stone location, and stone size. Thirty
      four patients from each group were selected for analysis. Pain was evaluated with
      an average visual analogue scale (VAS-avg) and maximum visual analogue scale (VAS
      max). Analgesic usage was also compared between the groups. RESULTS: All patients
      (n=34) in the supine group had radio-opaque stones compared with only 47.1% of
      the patients in the lateral group (n=16). The VAS-avg and VAS-max of the lateral
      group were significantly lower than those of the supine group (1.2+/-1.0 and
      3.1+/-1.7 for VAS-avg and 2.5+/-1.8 and 4.7+/-1.9 for VAS-max, respectively,
      p<0.05). However, analgesic usage between groups did not differ significantly
      (17.6% in the supine group vs. 5.9% in the lateral group, p=0.259). In a subgroup
      analysis confined to patients with radio-opaque stones, the supine group still
      suffered more pain. CONCLUSIONS: Patients with renal stones suffered more SWL
      related pain in the supine position than in the lateral position. During SWL,
      positioning of patients should be considered a predictive factor for SWL-related
      pain.

PMID- 23956830
TI  - Success rate of microsurgical multiple testicular sperm extraction and sperm
      presence in the ejaculate in korean men with y chromosome microdeletions.
AB  - PURPOSE: We assessed the frequency of azoospermia factor a (AZFa), AZFb, and AZFc
      deletions and examined correlations between the deletion sites and the success
      rates of sperm presence within the ejaculate and surgical sperm retrieval in
      Korean men. MATERIALS AND METHODS: A total of 1,919 azoospermic and severely
      oligozoospermic men were assessed for Y chromosome microdeletions. Among them,
      168 men with AZF deletions were identified and their medical records were
      reviewed. RESULTS: Of the total 168 men with AZF deletions, there were 13 with
      AZFa, 10 with AZFb, 95 with AZFc, 37 with AZFbc, and 13 with AZFabc deletions. Of
      the 95 men with isolated AZFc deletion, 51 had the presence of sperm in the
      ejaculate. Of the infertile men with any other deletion, however, only two
      patients (one man with AZFb deletion and another with AZFbc deletion) showed the
      presence of sperm in the ejaculate. The success rates for surgical sperm
      retrieval were 7.1% (1/14) in men with AZFbc deletion and 54.8% (17/31) in the
      isolated AZFc deletion group. No sperm was obtained from the patients with AZFa
      or AZFb deletions who underwent microsurgical sperm retrieval. In the isolated
      AZFc deletion group, there were significant differences between azoospermic and
      severely oligozoospermic patients in terms of testicular volume and serum levels
      of follicle-stimulating hormone and luteinizing hormone, whereas no significant
      differences were found when the group was divided by surgical sperm retrieval
      outcomes. CONCLUSIONS: Deletions of the AZFa and AZFb regions are associated with
      severe spermatogenetic impairment. However, more than half of men with an AZFc
      deletion had sperm within the ejaculate or testis for in vitro fertilization with
      intracytoplasmic sperm injection.

PMID- 23956831
TI  - Laparoendoscopic single-site urologic surgery in children less than 5 years of
      age.
AB  - PURPOSE: We report our experience with laparoendoscopic single-site (LESS)
      urological procedures in children less than 5 years of age. MATERIALS AND
      METHODS: Ten patients (11 procedures) underwent LESS through the umbilicus. Seven
      patients underwent nephrectomy and three patients underwent pyeloplasty (one
      simultaneous bilateral). R-port port (Advanced Surgical Concepts, Ireland) was
      used in nine cases, in one case, the Gelpoint access port (Applied Medical,
      Rancho Santa Margarita, CA, USA) was used. The Olympus Endoeye camera with
      coaxial light cable was used. The hilum was secured in all cases with Hem-o-Lok
      clips (Teleflex Medical, Research Triangle Park, NC, USA) except in one case in
      which an Endo GIA stapler (Covidien Surgical, Norwalk, CT, USA) was used.
      RESULTS: All procedures were technically successful. Accessory port (3 mm) was
      used in 3 patients. Mean age in nephrectomized patients was 3.14+/-1.7 years, the
      mean operative room time (ORT) was 97.5+/-12.54 minutes. In the pyeloplasty
      group, mean ORT was 192+/-47.16 minutes and mean age was 2.43+/-2.3 years.
      Bilateral pyeloplasty was done in a 4-month-old infant. The ORT in this case was
      180 minutes. A follow-up renogram done in the pyeloplasty patients (n=2) showed
      good drainage. Mean length of stay was 3.6 days (range, 3 to 6 days).The
      analgesic requirement was 23.86 mg (range, 12.5 to 50 mg) of diclofenac sodium.
      CONCLUSIONS: LESS is technically feasible in patients as young as 4 months of
      age. It has the potential to offer better cosmesis. This needs to be proved in
      further comparative studies. Development of miniature instruments will further
      the growth of LESS in this age group.

PMID- 23956832
TI  - Possible role of sonic hedgehog and epithelial-mesenchymal transition in renal
      cell cancer progression.
AB  - PURPOSE: Sonic hedgehog (Shh) signaling and epithelial-mesenchymal transition
      (EMT) are both known to relate to cancer progression. The purpose of this study
      was to investigate the role of Shh signaling and EMT in renal cell carcinoma
      (RCC). MATERIALS AND METHODS: Cell proliferation was assayed in RCC cell lines in
      the presence or absence of a Shh signaling stimulator, recombinant Shh (r-Shh)
      protein, or a Shh signaling inhibitor, cyclopamine. Real-time reverse
      transcription-polymerase chain reaction (RT-PCR) was performed to study the
      expression of EMT markers (E-cadherin, N-cadherin, and vimentin) and osteonectin.
      The expression of Ki-67, Gli-1, osteonectin, and EMT markers in nephrectomy
      specimens from RCC patients was also measured by immunohistochemical (IHC)
      staining. RESULTS: RCC cells showed enhanced cell proliferation by r-Shh protein,
      whereas cell proliferation was suppressed by the addition of cyclopamine in RenCa
      cells. Real-time RT-PCR showed that r-Shh suppressed the expression of E-cadherin
      and that this suppression was partly blocked by cyclopamine alone in RenCa cells.
      In the IHC results, osteonectin significantly correlated with vein sinus invasion
      (p=0.0218), and the expression of vimentin significantly correlated with
      lymphatic invasion (p=0.0392). CONCLUSIONS: Shh signaling and EMT play roles in
      RCC progression, and the Shh signaling inhibitor cyclopamine might be a possible
      molecular targeted therapeutic strategy for RCC.

PMID- 23956833
TI  - Squamous cell carcinoma in exstrophy of the bladder.
AB  - Exstrophy of the bladder is a rare congenital anomaly with an incidence of about
      1 per 50,000 newborns. The malignant potential of the exstrophied bladder mucosa
      is well known; 95% are adenocarcinomas, and 3% to 5% are squamous cell
      carcinomas. Most of the malignant tumors (60%) associated with an exstrophy of
      the bladder occur during the fourth and fifth decades of life. Of the remaining,
      about 20% each occur after 60 years and before 40 years. Here we present a case
      in which squamous cell carcinoma developed in an unrepaired exstrophy of the
      bladder. We present the management of the case and a brief review of the
      literature. 

PMID- 23956834
TI  - Corticosteroid therapy improves the outcome of semen analysis in an
      oligozoospermic patient with epididymal sarcoidosis.
AB  - Sarcoidosis is a multisystem, inflammatory disorder characterized by the presence
      of noncaseating epithelioid granulomas. Sarcoidosis can involve the genitourinary
      system by affecting the kidney and genitals. Most characteristic genital lesions
      proceed to granuloma and can comprise the epididymis, testis, and vas deferens.
      Few case reports have been published on this rare entity. We report a case in
      which a man presented with bilateral epididymal sarcoidosis and severe
      oligospermia. Corticosteroid treatment, which was applied in gradually decreasing
      doses for 6 months, dissolved the testicular granuloma. Consequently, semen
      analysis demonstrated a significant increase in the sperm count to within normal
      limits. 

PMID- 23956835
TI  - Synthesis and evaluation of a series of benzothiophene acrylonitrile analogs as
      anticancer agents.
AB  - A new library of small molecules with structural features resembling
      combretastatin analogs was synthesized and evaluated for anticancer activity
      against a panel of 60 human cancer cell lines. Three novel acrylonitrile analogs
      (5, 6 and 13) caused a significant reduction in cell growth in almost all the
      cell lines examined, with GI50 values generally in the range 10-100 nM. Based on
      the structural characteristics of similar drugs, we hypothesized that the
      cytotoxic activity was likely due to interaction with tubulin. Furthermore, these
      compounds appeared to overcome cell-associated P-glycoprotein (P-gp)-mediated
      resistance, since they were equipotent in inhibiting OVCAR8 and NCI/ADR-Res cell
      growth. Given that antitubulin drugs are among the most effective agents for the
      treatment of advanced prostate cancer we sought to validate the results from the
      60 cell panel by studying the representative analog 6 utilizing prostate cancer
      cell lines, as well as exploring the molecular mechanism of the cytotoxic action
      of this analog.

PMID- 23956836
TI  - Cellular Binding of Anionic Nanoparticles is Inhibited by Serum Proteins
      Independent of Nanoparticle Composition.
AB  - Nanoparticles used in biological applications encounter a complex mixture of
      extracellular proteins. Adsorption of these proteins on the nanoparticle surface
      results in the formation of a "protein corona," which can dominate the
      interaction of the nanoparticle with the cellular environment. The goal of this
      research was to determine how nanoparticle composition and surface modification
      affect the cellular binding of protein-nanoparticle complexes. We examined the
      cellular binding of a collection of commonly used anionic nanoparticles: quantum
      dots, colloidal gold nanoparticles, and low-density lipoprotein particles, in the
      presence and absence of extracellular proteins. These experiments have the
      advantage of comparing different nanoparticles under identical conditions. Using
      a combination of fluorescence and dark field microscopy, flow cytometry, and
      spectroscopy, we find that cellular binding of these anionic nanoparticles is
      inhibited by serum proteins independent of nanoparticle composition or surface
      modification. We expect these results will aid in the design of nanoparticles for
      in vivo applications.

PMID- 23956837
TI  - Regulation of Cell Proliferation by the Guanosine-Adenosine Mechanism: Role of
      Adenosine Receptors.
AB  - : A recent study (American Journal of Physiology-Cell Physiology 304: C406-C421,
      2013) suggests that extracellular guanosine increases extracellular adenosine by
      modifying the disposition of extracellular adenosine ("guanosine-adenosine
      mechanism") and that the guanosine-adenosine mechanism is not mediated by
      classical adenosine transport systems (SLC28 and SLC29 families) nor by classical
      adenosine-metabolizing enzymes. The present investigation had two aims: 1) to
      test the hypothesis that the "guanosine-adenosine mechanism" affects cell
      proliferation; and 2) to determine whether the transporters SLC19A1, SLC19A2,
      SLC19A3 or SLC22A2 (known to carrier guanosine analogues) might be responsible
      for the guanosine-adenosine mechanism. In the absence of added adenosine,
      guanosine had little effect on the proliferation of coronary artery vascular
      smooth muscle cells (vascular conduit cells) or preglomerular vascular smooth
      muscle cells (vascular resistance cells). However, in the presence of added
      adenosine (3 or 10 MUmol/L), guanosine (10 to 100 MUmol/L) decreased
      proliferation of both cell types, thus resulting in a highly significant
      (p<0.000001) interaction between guanosine and adenosine on cell proliferation.
      The guanosine-adenosine interaction on cell proliferation was abolished by 1,3
      dipropyl-8-(p-sulfophenyl)xanthine (adenosine receptor antagonist). Guanosine (30
      MUmol/L) increased extracellular levels of adenosine when adenosine (3 MUmol/L)
      was added to the medium. This effect was not reproduced by high concentrations of
      methotrexate (100 MUmol/L), thiamine (1000 MUmol/L), chloroquine (1000 MUmol/L)
      or acyclovir (10,000 MUmol/L), archetypal substrates for SLC19A1, SLC19A2,
      SLC19A3, and SLC22A2, respectively; and guanosine still increased adenosine
      levels in the presence of these compounds. CONCLUSION: The guanosine-adenosine
      mechanism affects cell proliferation and is not mediated by SLC19A1, SLC19A2,
      SLC19A3 or SLC22A2.

PMID- 23956838
TI  - Silent lipreading and covert speech production suppress processing of non
      linguistic sounds in auditory cortex.
AB  - Previous studies have suggested that speech motor system mediates suppression by
      silent lipreading of electromagnetic auditory cortex responses to pure tones at
      about 100 ms from sound onset. We used sparse sampling functional magnetic
      resonance imaging (fMRI) at 3 Tesla to map auditory-cortex foci of suppressant
      effects during silent lipreading and covert self-production. Streams of video
      clips were presented simultaneously with 1/3 octave noise bursts centered at 250
      Hz (low frequency, LF) or 2000 Hz (mid-frequency, MF), or during no auditory
      stimulation. In different conditions, the subjects were a) to press a button
      whenever they lipread the face articulate the same consecutive Finnish vowels
      /a/, /i/, /o/, and /y/, b) covertly selfproducing vowels while viewing still face
      image, or c) to press a button whenever a circle pictured on top of the lips
      expanded into oval shape of the same orientation twice in a row. The regions of
      interest (ROIs) within the superior temporal lobes of each hemisphere were
      defined by contrasting MF and LF stimulation against silence. Contrasting the
      nonlinguistic (i.e., expanding circle) vs. linguistic (i.e., lipreading and
      covert self-production) conditions within these ROIs showed significant
      suppression of hemodynamic activity to MF sounds in the linguistic condition in
      left hemisphere first transverse sulcus (FTS) and right hemisphere superior
      temporal gyrus (STG) lateral to Heschl's sulcus (HS). These findings suggest that
      the speech motor system mediates suppression of auditory-cortex processing of non
      linguistic sounds during silent lipreading and covert self-production in left
      hemisphere FST and right hemisphere STG lateral to HS.

PMID- 23956840
TI  - Cardiac troponin elevation predicts mortality in patients undergoing orthotopic
      liver transplantation.
AB  - Introduction. While patients undergoing orthotopic liver transplantation (OLT)
      have high cardiovascular event rates, preoperative risk stratification may not
      necessarily predict those susceptible patients. Troponin T (TnT) may help predict
      patients at risk for cardiovascular complications. Methods. Consecutive patients
      undergoing OLT at Mayo Clinic in Florida between 1998 and 2010 who had TnT
      obtained within 10 days following surgery were included. Three groups were
      compared based on TnT level: (1) normal (TnT <=0.01 ng/mL), (2) intermediate (TnT
      0.02-0.11 ng/mL), and (3) elevated (TnT >0.11 ng/mL). Overall and cardiovascular
      mortality was assessed. Results. Of the 78 patients included, there was no
      difference in age, gender, severity of liver disease, and echocardiographic
      findings. Patients in the normal and intermediate TnT groups had a lower overall
      mortality rate (14.3% and 0%, resp.) when compared with those with elevated TnT
      (50%; P = 0.001). Patients in the elevated TnT group had a cardiovascular
      mortality rate of 37.5% compared with 1.4% in the other groups combined (P <
      0.01). The elevated TnT group had a much higher mortality rate when compared with
      those in the intermediate group (P < 0.0001). Conclusion. TnT may accurately help
      risk stratify patients in the early postoperative setting to better predict
      cardiovascular complications. 

PMID- 23956839
TI  - PRENATAL INFECTION, MATERNAL IMMUNE ACTIVATION, AND RISK FOR SCHIZOPHRENIA.
AB  - A body of epidemiological literature has suggested an association between
      prenatal infection, subsequent maternal immune activation (MIA), and later risk
      of schizophrenia. These epidemiological studies have inspired preclinical
      research using rodent and primate models of prenatal infection and MIA. The
      findings from these preclinical studies indicate that severe infection and immune
      activation during pregnancy can negatively impact offspring brain development and
      impair adult behavior. This review aims to summarize the major epidemiological
      and preclinical findings addressing the connection between prenatal infection and
      immune activation and later risk of developing schizophrenia, as well as the more
      limited literature addressing the mechanisms by which this gestational insult
      might affect offspring neurodevelopment. Finally, directions for future research
      will be discussed.

PMID- 23956841
TI  - Salivary Glands Proteins Expression of Anopheles dirus A Fed on Plasmodium vivax-
      and Plasmodium falciparum-Infected Human Blood.
AB  - Mosquitoes are able to adapt to feed on blood by the salivary glands which
      created a protein that works against the haemostasis process. This study aims to
      investigate the salivary glands proteins expression of 50 adult female An. dirus
      A mosquitoes, a main vector of malaria in Thailand, each group with an age of 5
      days which were artificial membrane fed on sugar, normal blood, blood infected
      with P. vivax, and blood infected with P. falciparum. Then mosquito salivary
      gland proteins were analyzed by SDS-PAGE on days 0, 1, 2, 3, and 4 after feeding.
      The findings revealed that the major salivary glands proteins had molecular
      weights of 62, 58, 43, 36, 33, 30, and 18 kDa. One protein band of approximately
      13 kDa was found in normal blood and blood infected with P. vivax fed on day 0. A
      stronger protein band, 65 kDa, was expressed from the salivary glands of
      mosquitoes fed with P. vivax- or P. falciparum-infected blood on only day 0, but
      none on days 1 to 4. The study shows that salivary glands proteins expression of
      An. dirus may affect the malaria parasite life cycle and the ability of
      mosquitoes to transmit malaria parasites in post-24-hour disappearance
      observation. 

PMID- 23956842
TI  - Intraocular Microsurgical Forceps (20, 23, and 25 gauge) Membrane Peeling Forces
      Assessment.
AB  - Background. To assess the peeling forces exerted by different calibers of
      microsurgical forceps on an experimental model of epiretinal membrane. Methods. A
      model of epiretinal membrane was constructed using thin cellulose paper and
      heptanes-isopropyl alcohol 1% mixture. The model was mounted on a force censoring
      device. Subsequently, flaps were created with three different microsurgical
      forceps of different calibers. We recorded the number of attempts, the duration
      of the event, and the pushing and the pulling forces during the peeling. The
      results were compared by a one-way ANOVA and a Fisher unprotected least
      significant difference test with an alpha value of 0.05 for statistically
      significance. Results. There was a statistical significant difference on the
      pulling and pushing forces between the 25 gauge (13.79 mN; -13.27 mN) and the 23
      (6.63 mN; -5.76 mN) and 20 (5.02 mN; -5.30 mN) gauge, being greater in the first
      (P < 0.001). There were no differences in the duration of all events, meaning
      that all the forces were measured within the same period of time. Conclusions.
      The 25 gauge microsurgical forceps exerted the greatest mechanical stress over
      our simulated epiretinal membrane model and required more attempts to create a
      surgical suitable flap. The clinical implication of this finding is still to be
      determined. 

PMID- 23956843
TI  - Participatory action research in the implementing process of evidence-based
      intervention to prevent childhood obesity: project design of the "Healthy Future"
      study.
AB  - OBJECTIVE: To describe the design of the developmental project Healthy Future
      that aims to implement a new evidence-based program for the prevention of
      childhood obesity and collaboration and sharing of work between specialist and
      community health care professionals in parts of a county in western Norway.
      METHODS: Comprehensive participatory planning and evaluation (CPPE) process as an
      action-oriented research approach was chosen, using mixed data sources, mixed
      methods, and triangulation. DISCUSSION: A bottom-up approach might decrease the
      barriers when new evidence-based childhood prevention interventions are going to
      be implemented. It is crucial not only to build partnership and shared
      understanding, motivation, and vision, but also to consider the frames of the
      organizations, such as competencies, and time to carry out the interventions at
      the right level of health care service and adapt to the overweight children and
      their families needs. CONCLUSION: The developmental process of new health care
      programs is complex and multileveled and requires a framework to guide the
      process. By CPPE approach evidence-based health care practice can be delivered
      based on research, user knowledge, and provider knowledge in the field of
      childhood overweight and obesity in a certain context.

PMID- 23956844
TI  - Youth understanding of healthy eating and obesity: a focus group study.
AB  - INTRODUCTION: Given the high prevalence of childhood obesity in the United
      States, we aimed to investigate youth's understanding of obesity and to
      investigate gaps between their nutritional knowledge, dietary habits, and
      perceived susceptibility to obesity and its co-morbidities. METHODS: A marketing
      firm contracted by Children's Healthcare of Atlanta facilitated a series of focus
      group discussions (FGD) to test potential concepts and sample ads for the
      development of an obesity awareness campaign. Data were collected in August and
      September of 2010 with both overweight and healthy weight 4th-5th grade and 7th
      8th grade students. We conducted a secondary analysis of the qualitative FGD
      transcripts using inductive thematic coding to identify key themes related to
      youth reports of family eating habits (including food preparation, meal
      frequency, and eating environment), perceived facilitators and barriers of
      healthy diet, and knowledge about obesity and its complications. RESULTS: Across
      focus group discussions, mixed attitudes about healthy eating, low perceived risk
      of being or becoming obese, and limited knowledge about the health consequences
      of obesity may contribute to the rising prevalence of obesity among youth in
      Georgia. Most youth were aware that obesity was a problem; yet most overweight
      youth felt that their weight was healthy and attributed overweight to genetics or
      slow metabolism. CONCLUSIONS: Our analysis suggests that urban youth in Georgia
      commonly recognize obesity as a problem, but there is less understanding of the
      link to lifestyle choices or the connection to future morbidities, suggesting a
      need for education to connect lifestyle behaviors to development of obesity.

PMID- 23956845
TI  - Eating behaviors and overweight among adolescents: a population-based survey in
      Japan.
AB  - OBJECTIVES: The aim of the present study was to investigate the relationship
      between eating behaviors and overweight among population-based adolescents in
      Japan. METHODS: Study subjects comprised adolescents in the seventh grade (age
      range, 12-13 years) from Ina, a town in Saitama Prefecture, Japan, between 1999
      and 2008. The height and weight of the subjects were measured, and information
      concerning eating behaviors (eating speed and eating until full) was obtained
      using a self-administered questionnaire. RESULTS: Among boys (n = 1586), fast
      eating speed significantly increased the odds ratio (OR) for overweight when
      compared with medium eating speed, regardless of eating until full or not;
      moreover, a more marked increase in the OR was observed among boys eating until
      full (OR: 2.78, 95% confidence interval: 1.76-4.38) than among those not eating
      until full (2.43, 1.41-4.20). Among girls (n = 1542), fast eating speed led to a
      significant increase in the OR in those eating until full; however, no
      significant increases were observed in the OR in those eating quickly and not
      until full. CONCLUSIONS: Among adolescents, fast eating speed was associated with
      overweight; furthermore, the combination of both fast eating speed and eating
      until full may have a significant effect on overweight.

PMID- 23956847
TI  - Preliminary studies demonstrating acetoclastic methanogenesis in a rat colonic
      ring model.
AB  - Washed rat colonic rings were incubated in closed flasks under N2 at physiologic
      pH and temperature levels. In the absence of an exogenous substrate, negligible
      H2 but some CH4 concentrations were detected in vitro after one hour of
      incubation, but high concentrations (H2 > 100 ppm, CH4 > 10 ppm) of both gases
      were found after 24 hours of culture. Production of H2 and CH4 by the washed
      colonic rings was stimulated by lactose addition. Maximum H2 production occurred
      at about pH 7.0, while maximum CH4 production occurred between pH 4.0 and 6.0.
      The increased production of both gases at 24 hours was associated with dramatic
      increases (10(4)-fold) in anaerobic bacteria colony counts on the colonic rings
      and in the incubation media, as well as dramatic increases (100-fold) in acetate
      concentrations in the media, while lactate concentrations first rose and then
      fell significantly. These results suggest that gas production in colonic ring
      preparations is subject to quantitative changes in microbiota, pH, and metabolite
      formation analogous to in vivo conditions. In addition, microbiota firmly
      attached to colonic tissue appears to utilize colonic tissue to support its
      growth in the absence of an exogenous substrate. 

PMID- 23956846
TI  - Sleeve gastrectomy and gastroesophageal reflux disease.
AB  - Bariatric surgery, when combined with lifestyle and medical interventions, is a
      common and successful treatment modality in the obese patient. Laparoscopic
      sleeve gastrectomy is one such procedure that has increased in popularity as a
      definitive bariatric operation. Although laparoscopic sleeve gastrectomy has been
      shown to be effective in producing weight loss and improving type 2 diabetes
      mellitus, its effect on gastroesophageal reflux disease (GERD) has been
      inconsistent. This paper aims to summarize the available literature regarding
      GERD prevalence following laparoscopic sleeve gastrectomy, 8 studies demonstrate
      increased GERD prevalence, and 5 demonstrate decreased GERD prevalence following
      laparoscopic sleeve gastrectomy. The relationship between GERD and SG is complex
      and no clear relationship exists. The anatomic and physiologic changes caused by
      laparoscopic sleeve gastrectomy are discussed in the context of these
      inconsistent results. 

PMID- 23956848
TI  - Comparative Effectiveness of Darunavir 1,200 mg Daily and Approved Dosing
      Strategies for Protease Inhibitor-Experienced Patients.
AB  - Background. HIV protease inhibitors exhibit concentration-dependent viral
      inhibition. Higher once daily doses of darunavir boosted with ritonavir (DRV/r)
      may achieve viral suppression in place of twice daily dosing. International
      antiretroviral adherence guidelines recommend once daily regimens whenever
      possible. We present data on virologic suppression achieved with DRV 1,200 mg and
      ritonavir 100 mg once daily compared to approved DRV regimens. Methods. This
      retrospective observational study included all patients treated with DRV after
      documented use of another protease inhibitor at an urban immunodeficiency clinic.
      Data collection from inception of DRV use in August 2006 through March 2012
      included patient demographics, viral loads, CD4+ cell counts, and resistance test
      results. The primary outcome of virologic suppression was defined as <50
      copies/mL at 24 weeks. Differences in baseline characteristics and virologic
      outcomes across dosing groups were analyzed via one-way analysis of variance.
      Results. One hundred and thirty-five patients were included in the ITT analysis.
      Most patients had no known DRV RAMs at baseline. Virologic suppression rate was
      not different among treatment groups: 53.6% of patients on 1,200 mg daily, 52.3%
      on 600 mg twice daily, and 42.9% on 800 mg daily (P = 0.568). Conclusions.
      Darunavir 1,200 mg daily should be investigated for use in protease inhibitor
      experienced patients. 

PMID- 23956849
TI  - Utilization of and Barriers to HIV and MCH Services among Community ART Group
      Members and Their Families in Tete, Mozambique.
AB  - Mozambique continues to face many challenges in HIV and maternal and child health
      care (MCH). Community-based antiretroviral treatment groups (CAG) enhance
      retention to care among members, but whether such benefits extend to their
      families and to MCH remains unclear. In 2011 we studied utilization of HIV and
      MCH services among CAG members and their family aggregates in Changara,
      Mozambique, through a mixed-method assessment. We systematically revised all
      patient-held health cards from CAG members and their non-CAG family aggregate
      members and conducted semistructured group discussions on MCH topics.
      Quantitative data were analysed in EPI-Info. Qualitative data were manually
      thematically analysed. Information was retrieved from 1,624 persons, of which 420
      were CAG members (26%). Good compliance with HIV treatment among CAG members was
      shared with non-CAG HIV-positive family members on treatment, but many family
      aggregate members remained without testing, and, when HIV positive, without HIV
      treatment. No positive effects from the CAG model were found for MCH service
      utilization. Barriers for utilization mentioned centred on insufficient
      knowledge, limited community-health facility collaboration, and structural health
      system limitations. CAG members were open to include MCH in their groups,
      offering the possibility to extend patient involvement to other health needs. We
      recommend that lessons learnt from HIV-based activism, patient involvement, and
      community participation are applied to broader SRH services, including MCH care. 

PMID- 23956850
TI  - Same-Day CD4 Testing to Improve Uptake of HIV Care and Treatment in South Africa:
      Point-of-Care Is Not Enough.
AB  - Background. We evaluated whether a pilot program providing point-of-care (POC),
      but not rapid, CD4 testing (BD FACSCount) immediately after testing HIV-positive
      improved retention in care. Methods. We conducted a retrospective record review
      at the Themba Lethu Clinic in Johannesburg, South Africa. We compared all walk-in
      patients testing HIV-positive during February, July 2010 (pilot POC period) to
      patients testing positive during January 2008-February 2009 (baseline period).
      The outcome for those with a <=250 cells/mm(3) when testing HIV-positive was
      initiating ART <16 weeks after HIV testing. Results. 771 patients had CD4 results
      from the day of HIV testing (421 pilots, 350 baselines). ART initiation within 16
      weeks was 49% in the pilot period and 46% in the baseline period. While all 421
      patients during the pilot period should have been offered the POC test, patient
      records indicate that only 73% of them were actually offered it, and among these
      patients only 63% accepted the offer. Conclusions. Offering CD4 testing using a
      point-of-care, but not rapid, technology and without other health system changes
      had minor impacts on the uptake of HIV care and treatment. Point-of-care
      technologies alone may not be enough to improve linkage to care and treatment
      after HIV testing. 

PMID- 23956851
TI  - Feasibility and Acceptability of a Real-Time Adherence Device among HIV-Positive
      IDU Patients in China.
AB  - We collected data on feasibility and acceptability of a real-time web-linked
      adherence monitoring container among HIV-positive injection drug users (IDU) in
      China. "Wisepill" uses wireless technology to track on-time medication dosing.
      Ten patients on antiretroviral therapy (ART) at the Guangxi CDC HIV clinic in
      Nanning, China, used Wisepill for one ART medication for one month. We monitored
      device use and adherence and explored acceptability of the device among patients.
      Mean adherence was 89.2% (SD 10.6%). Half of the subjects reported a positive
      overall experience with Wisepill. Seven said that it was inconvenient, supported
      by comments that it was large and conspicuous. Five worried about disclosure of
      HIV status due to the device; no disclosures were reported. Twelve signal lapses
      occurred (5.4% of prescribed doses), of which one was due to technical reasons,
      nine to behavioral reasons (both intentional and unintentional), and two to
      unclear reasons. Although the technical components must be monitored carefully,
      and acceptability to patients presents challenges which warrant further
      exploration, the Wisepill device has potential for adherence interventions that
      deliver rapid adherence-support behavioral feedback directly to patients,
      including IDU. The use of wireless technology appears uniquely promising for
      providing time-sensitive communication on patient behavior that can be harnessed
      to maximize the benefits of HIV treatment. 

PMID- 23956852
TI  - Sleep Difficulties Are Correlated with Emotional Problems following Loss and
      Residual Symptoms of Effective Prolonged Grief Disorder Treatment.
AB  - There is preliminary evidence that poor sleep quality is associated with
      emotional problems following loss, including symptoms of prolonged grief disorder
      (PGD) and depression. We conducted two studies to improve existing knowledge
      about the role of sleep difficulties in recovery from loss. Study 1 that relied
      on self-reported data from a heterogeneous sample of 177 bereaved individuals
      replicated prior findings of a linkage between increased sleep difficulties and
      increased PGD severity. This study also suggested that sleep difficulties are
      more strongly associated with depression than with PGD. In Study 2, we examined
      whether prior evidence that sleep complaints are a residual symptom of PGD
      treatment could be replicated in a sample of 43 bereaved individuals who
      underwent cognitive behavioural therapy for PGD. Outcomes showed that, although
      sleep difficulties declined significantly during this cognitive behavioural
      therapy, after this therapy, over half of all patients still had sleep
      difficulties above the average sleep difficulties observed in the general Dutch
      population. 

PMID- 23956853
TI  - Measuring comorbidity in cardiovascular research: a systematic review.
AB  - Background. Everything known about the roles, relationships, and repercussions of
      comorbidity in cardiovascular disease is shaped by how comorbidity is currently
      measured. Objectives. To critically examine how comorbidity is measured in
      randomized controlled trials or clinical trials and prospective observational
      studies in acute myocardial infarction (AMI), heart failure (HF), or stroke.
      Design. Systematic review of studies of hospitalized adults from MEDLINE CINAHL,
      PsychINFO, and ISI Web of Science Social Science databases. At least two
      reviewers screened and extracted all data. Results. From 1432 reviewed abstracts,
      26 studies were included (AMI n = 8, HF n = 11, stroke n = 7). Five studies used
      an instrument to measure comorbidity while the remaining used the presence or
      absence of an unsubstantiated list of individual diseases. Comorbidity data were
      obtained from 1-4 different sources with 35% of studies not reporting the source.
      A year-by-year analysis showed no changes in measurement. Conclusions. The
      measurement of comorbidity remains limited to a list of conditions without stated
      rationale or standards increasing the likelihood that the true impact is
      underestimated. 

PMID- 23956854
TI  - Developing a culture to facilitate research capacity building for clinical nurse
      consultants in generalist paediatric practice.
AB  - This paper reports a research capacity building exercise with a group of CNCs
      practicing in the speciality of paediatrics in New South Wales (NSW), Australia.
      It explores the first step in building a research culture, through identifying
      the research priorities of members of the NSW Child Health Networks Paediatric
      Clinical Nurse Consultant group, and this forms the major focus of this paper. A
      nominal group technique (NGT) was utilised with sixteen members to identify
      research topics for investigation which were considered a priority for improving
      children's health care. The group reviewed and prioritised 43 research topics in
      children's health which were identified in the literature. As a result of
      conducting this research prioritisation exercise, the group chose two research
      topics to investigate: reasons for children representing to the Emergency
      Department and a comparison of the use of high-flow and low-flow nasal prongs in
      children with bronchiolitis. The research team will continue to mentor the nurses
      throughout their research projects which resulted from the NGT. One bridge to
      leadership development in enhancing patient care is translating knowledge to
      practice and policy development. This study leads the way for a group of CNCs in
      paediatric nursing to combine their research capacity and influence clinical
      knowledge. 

PMID- 23956855
TI  - Differences in Epidural and Analgesic Use in Patients with Apparent Stage I
      Endometrial Cancer Treated by Open versus Laparoscopic Surgery: Results from the
      Randomised LACE Trial.
AB  - Objectives. We compared postoperative analgesic requirements between women with
      early stage endometrial cancer treated by total abdominal hysterectomy (TAH) or
      total laparoscopic hysterectomy (TLH). Methods. 760 patients with apparent stage
      I endometrial cancer were treated in the international, multicentre, prospective
      randomised trial (LACE) by TAH (n = 353) or TLH (n = 407) (2005-2010). Epidural,
      opioid, and nonopioid analgesic requirements were collected until ten months
      after surgery. Results. Baseline demographics and analgesic use were comparable
      between treatment arms. TAH patients were more likely to receive epidural
      analgesia than TLH patients (33% versus 0.5%, P < 0.001) during the early
      postoperative phase. Although opioid use was comparable in the TAH versus TLH
      groups during postoperative 0-2 days (99.7% versus 98.5%, P = 0.09), a
      significantly higher proportion of TAH patients required opioids 3-5 days (70%
      versus 22%, P < 0.0001), 6-14 days (35% versus 15%, P < 0.0001), and 15-60 days
      (15% versus 9%, P = 0.02) after surgery. Mean pain scores were significantly
      higher in the TAH versus TLH group one (2.48 versus 1.62, P < 0.0001) and four
      weeks (0.89 versus 0.63, P = 0.01) following surgery. Conclusion. Treatment of
      early stage endometrial cancer with TLH is associated with less frequent use of
      epidural, lower post-operative opioid requirements, and better pain scores than
      TAH. 

PMID- 23956856
TI  - Effect of abdominoplasty in the lipid profile of patients with dyslipidemia.
AB  - Introduction. Dyslipidemia like other chronic degenerative diseases is pandemic
      in Latin America and around the world. A lot of patients asking for body
      contouring surgery can be sick without knowing it. Objective. Observe the lipid
      profile of patients with dyslipidemia, before and three months after an
      abdominoplasty. Methods. Patients candidate to an abdominoplasty without morbid
      obesity were followed before and three months after the surgery. We compared the
      lipid profile, glucose, insulin, and HOMA (cardiovascular risk marker) before and
      three months after the surgery. We used Student's t test to compare the results.
      A P value less than 0.05 was considered as significant. Results. Twenty-six
      patients were observed before and after the surgery. At the third month, we found
      only statistical differences in LDL and triglyceride values (P 0.04 and P 0.03).
      The rest of metabolic values did not reach statistical significance. Conclusion.
      In this group of patients with dyslipidemia, at the third month, only LDL and
      triglyceride values reached statistical significances. There is no significant
      change in glucose, insulin, HOMA, cholesterol, VLDL, or HDL. 

PMID- 23956857
TI  - The effect of intravenous dexamethasone and lidocaine on propofol-induced
      vascular pain: a randomized double-blinded placebo-controlled trial.
AB  - Background. The mechanism for pain associated with intravenous administration of
      propofol is believed to be related to the release of nitric oxide. We
      hypothesized that pain following propofol injection would be reduced by
      pretreatment with dexamethasone. Methods. One hundred fourteen female subjects
      received 5 mL of preservative-free saline, 0.5 mg . kg(-1) of lignocaine
      hydrochloride 10 mg . mL(-1) or 0.25 mg . kg(-1) of dexamethasone, intravenously,
      following exsanguination and occlusion of the veins of the arm. This was followed
      by a 0.5 mg . kg(-1) injection of propofol. Pain scores, facial grimacing, arm
      withdrawal, and vocalization were recorded prior to and at 15 and 30 seconds
      following the injection of propofol. Results. The incidence of moderate to severe
      pain following the injection of propofol was significantly decreased with both
      lidocaine and dexamethasone. Hand withdrawal was also significantly decreased in
      comparison to saline. Conclusion. Low dose dexamethasone is commonly used as an
      antiemetic, and, in larger doses, it has been demonstrated to provide prolonged
      postoperative analgesia. At higher analgesic doses, dexamethasone may also reduce
      pain associated with the injection of propofol. This effect is probably related
      to the effect of the steroid on nitric oxide production associated with
      intravenous propofol injection. 

PMID- 23956858
TI  - Preoperative high-dose steroid has long-term beneficial effects for myasthenia
      gravis.
AB  - Previous studies addressing preoperative steroid treatment have revealed that
      control of myasthenia gravis (MG) with steroids prior to surgery appeared to
      stabilize postoperative status. The purpose of our study was to clarify the
      clinical benefits of the preoperative programmed high-dose steroid treatment on
      the long-term outcomes of MG patients. We retrospectively reviewed the records of
      171 MG patients who were followed up after undergoing thymectomy in our hospital
      between 1988 and 2006. One hundred and thirteen patients in the programmed
      treatment group had received preoperative steroid treatment, while 58 patients
      received no steroid treatment during the preoperative period. Clinical remission,
      which was defined as the achievement of the modified pharmacologic remission (PR)
      for at least 1 year, and clinical benefits were compared between the two groups.
      With regard to the remission after thymectomy, Kaplan-Meier life-table curves for
      patients in the preoperative steroid treatment group versus those for patients in
      the no steroid preoperative treatment group revealed a significantly higher
      probability of the PR in the preoperative steroid treatment group (log-rank test,
      P < 0.01). This study might be the first, as per our knowledge, to indicate that
      preoperative programmed high-dose steroid treatment has long-term beneficial
      effects for MG patients. 

PMID- 23956859
TI  - Sensory Response Patterns in Nonverbal Children with ASD.
AB  - We sought to examine concurrent and longitudinal associations between sensory
      response patterns (i.e., hyperresponsiveness, hyporesponsiveness, and sensory
      seeking) and verbal status of young children with autism spectrum disorder (ASD)
      as a potential factor influencing the development of verbal communication.
      Seventy-nine children with ASD (verbal, n = 29; nonverbal, n = 50) were assessed
      using cross-sectional analyses (Study 1), and 14 children with ASD (verbal, n =
      6; nonverbal, n = 8) were assessed using prospective longitudinal analyses (Study
      2). Data were collected regarding sensory response patterns and verbal ability.
      Hyporesponsiveness and sensory seeking behaviors were associated with verbal
      status in both cross-sectional and longitudinal analyses; nonverbal children were
      more likely to demonstrate higher hyporesponsive and sensory seeking patterns.
      Hyperresponsiveness did not significantly differ between verbal and nonverbal
      groups in either design. Sensory hyporesponsiveness and seeking behaviors may be
      important factors hindering the development of functional verbal communication in
      children with ASD. Unusual sensory responsiveness can often be observed before
      the onset of speech and may yield important prognostic capabilities as well as
      inform early interventions targeting verbal communication or alternative
      communication options in young children with ASD. 

PMID- 23956860
TI  - Letrozole Potentiates Mitochondrial and Dendritic Spine Impairments Induced by
      beta Amyloid.
AB  - Reduced estrogens, either through aging or postsurgery breast cancer treatment
      with the oral nonsteroidal aromatase inhibitor letrozole, are linked with
      declined cognitive abilities. However, a direct link between letrozole and
      neuronal deficits induced by pathogenic insults associated with aging such as
      beta amyloid (Abeta 1-42) has not been established. The objective of this study
      was to determine if letrozole aggravates synaptic deficits concurrent with Abeta
      1-42 insult. We examined the effects of letrozole and oligomeric Abeta 1-42
      treatment in dissociated and organotypic hippocampal slice cultures. Changes in
      glial cell morphology, neuronal mitochondria, and synaptic structures upon
      letrozole treatment were monitored by confocal microscopy, as they were shown to
      be affected by Abeta 1-42 oligomers. Oligomeric Abeta 1-42 or letrozole alone
      caused decreases in mitochondrial volume, dendritic spine density, synaptophysin
      (synaptic marker), and the postsynaptic protein, synaptopodin. Here, we
      demonstrated that mitochondrial and synaptic structural deficits were exacerbated
      when letrozole therapy was combined with Abeta 1-42 treatment. Our novel findings
      suggest that letrozole may increase neuronal susceptibility to pathological
      insults, such as oligomeric Abeta 1-42 in Alzheimer's disease (AD). These changes
      in dendritic spine number, synaptic protein expression, and mitochondrial
      morphology may, in part, explain the increased prevalence of cognitive decline
      associated with aromatase inhibitor use. 

PMID- 23956861
TI  - Maternal cardiac arrest: a practical and comprehensive review.
AB  - Cardiac arrest during pregnancy is a dedicated chapter in the American Heart
      Association Guidelines for Cardiopulmonary Resuscitation and Emergency
      Cardiovascular Care; however, a robust maternal cardiac arrest knowledge
      translation strategy and emergency response plan is not usually the focus of
      institutional emergency preparedness programs. Although maternal cardiac arrest
      is rare, the emergency department is a high-risk area for receiving pregnant
      women in either prearrest or full cardiac arrest. It is imperative that
      institutions review and update emergency response plans for a maternal arrest.
      This review highlights the most recent science, guidelines, and recommended
      implementation strategies related to a maternal arrest. The aim of this paper is
      to increase the understanding of the important physiological differences of, and
      management strategies for, a maternal cardiac arrest, as well as provide
      institutions with the most up-to-date literature on which they can build
      emergency preparedness programs for a maternal arrest. 

PMID- 23956862
TI  - Anterior-Posterior Instability of the Knee Following ACL Reconstruction with Bone
      Patellar Tendon-Bone Ligament in Comparison with Four-Strand Hamstrings
      Autograft.
AB  - Purpose. To evaluate anterior-posterior knee laxity using two different
      autografts. Material-Methods. 40 patients, (34 males and 6 women), 17-54 years
      old (mean: 31), were included in the present study. Group A (4SHS = 20) underwent
      reconstruction using four-strand hamstrings, and group B (BPBT = 20) underwent
      reconstruction using bone-patellar tendon-bone autograft. Using the KT-1000
      arthrometer, knee instability was calculated in both knees of all patients
      preoperatively and 3, 6, and 12 months after surgery at the ACL-operated knee.
      The contralateral healthy knee was used as an internal control group. Results.
      Anterior-posterior instability using the KT1000 Arthrometer was found to be
      increased after ACL insufficiency. The recorded laxity improved after
      arthroscopic ACL reconstruction in both groups. However, statistically
      significant greater values were detected in the bone-patellar tendon-bone group,
      which revealed reduction of anteroposterior stability values to an extent, where
      no statistical significance with the normal values even after 3 months after
      surgery was observed. Conclusions. Anterior-Posterior instability of the knee
      improved significantly after arthroscopic ACL reconstruction. The bone-patellar
      tendon-bone graft provided an obvious greater stability. 

PMID- 23956863
TI  - The use of family history in primary health care: a qualitative study.
AB  - The aim of this study is to describe how Belgian family physicians register and
      use the family history data of their patients in daily practice. Qualitative in
      depth semistructured one-to-one interviews were conducted including 16 family
      physicians in Belgium. These interviews were recorded, transcribed, and analysed.
      Recurring themes were identified and compared with findings from the existing
      literature. All interviewed family physicians considered the family history as an
      important part of the medical records. Half of the surveyed physicians confirmed
      knowing the family history of at least 50% of their patients. The data on family
      history were mainly collected during the first consultations with the patient.
      The majority of physicians did not use a standardised questionnaire or form to
      collect and to record the family history. To estimate the impact of a family
      history, physicians seldom use official guidance or resources. Physicians
      perceived a lack of time and unreliable information provided by their patients as
      obstacles to collect and interpret the family history. Solutions that foster the
      use of family history data were identified at the level of the physician and also
      included the development of specific instruments integrated within the electronic
      medical record. 

PMID- 23956864
TI  - Sleep and military members: emerging issues and nonpharmacological intervention.
AB  - Background. Many individuals who work in the military experience sleep deficiency
      which presents a significant problem given the nature of their work. The cause of
      their sleep problems is likely multifactorial, stemming from the interplay
      between their personal health, habits and lifestyle juxtaposed with the stress of
      their military work such as emotional and physical trauma experienced in service.
      Objective. To present an overview of sleep deficiency in military members (MMs)
      and review of nonpharmacological treatment options. Discussion. Although there
      are a number of promising nonpharmacological treatment options available for
      people working in the military who experience problems sleeping, testing
      interventions within the context of the military are still in the early stages.
      Further research utilizing rigorous design and standardized, context appropriate
      outcome measures is needed to help treat this burgeoning problem. 

PMID- 23956865
TI  - The Performance of ICDAS-II Using Low-Powered Magnification with Light-Emitting
      Diode Headlight and Alternating Current Impedance Spectroscopy Device for
      Detection of Occlusal Caries on Primary Molars.
AB  - Early detection of occlusal caries in children is challenging for the dentists,
      because of the morphology of pit and fissures. The aim of this study was to
      compare in vitro the diagnostic performance of low-powered magnification with
      light-emitting diode headlight (LPMLED) using ICDAS-II criteria and AC Impedance
      Spectroscopy (ACIS) device, on occlusal surfaces of primary molars. The occlusal
      surfaces of 18 extracted primary molars were examined blindly by two examiners.
      The teeth were sectioned and examined under light microscopy using Downer's
      histological criteria as gold standard. Good to excellent inter- and
      intraexaminer reproducibility, higher sensitivity, specificity, and AUC values
      were achieved by LPMLED at D1 threshold. Also the relationship between histology
      and LPMLED was statistically significant. In conclusion visual aids have the
      potential to improve the performance of early caries detection and clinical
      diagnostics in children. Despite its potential, ACIS device should be considered
      as an adjunct method in detecting caries on primary teeth. 

PMID- 23956866
TI  - Effect of diazepam on severity of acute pancreatitis: possible involvement of
      peripheral benzodiazepine receptors.
AB  - Acute pancreatitis is a lethal inflammatory condition of pancreas with high
      mortality rate. There is a pressing need for research to explore active agents
      and novel mechanisms involving in the treatment of pancreatitis. Clinical studies
      have shown after the initial acinar cell injury plasma levels of pro-inflammatory
      cytokines are elevated in patients with acute pancreatitis and the degree of
      cytokine elevation correlates with disease severity. Diazepam may decrease
      interleukin release from macrophages, suppress neutrophil activities, and exhibit
      anti-inflammatory effects. So it is expected that in vivo pretreatment of acute
      pancreatitis with different doses of diazepam can attenuate its severity. Thus,
      we evaluated the effects of diazepam, intraperitoneally (5, 10, and 20 mg/kg
      i.p.), intracerebroventricularly (ICV 10  MU g), and concurrently with flumazenil
      (1 mg/kg) on cerulein-induced acute pancreatitis in mice. Interestingly, the
      pretreatment with diazepam (5 mg/kg i.p.) reduced significantly the inflammatory
      response of acute pancreatitis by ameliorating pancreatic edema, amylase and
      lipase serum levels, myeloperoxidase activity, pancreatic TNF-alpha, and
      pathological alteration compared to control group. Diazepam i.c.v. was
      ineffective, suggesting that central benzodiazepine receptors have no significant
      role in this property. These results demonstrate that pretreatment with diazepam
      exhibits anti-inflammatory property in cerulein-induced acute pancreatitis
      possibly through peripheral benzodiazepine receptors. 

PMID- 23956867
TI  - Endometriosis: a disease that remains enigmatic.
AB  - Endometriosis, a gynecologic pathology, is defined by the presence of a tissue
      similar to uterine endometrium, which is located in places other than
      physiologically appropriate. These endometrial heterotopic islets contain glands
      and stroma and are functionally capable of responding to exogenous, endogenous,
      or local hormonal stimuli. Endometriosis affects 8%-10% of women of reproductive
      age; in 30% of the women, the condition is associated with primary or secondary
      infertility. In several instances, endometriosis persists as a minimal or mild
      disease, or it can resolve on its own. Other cases of endometriosis show severe
      symptomatology that ends when menopause occurs. Endometriosis can, however,
      reactivate in several postmenopausal women when iatrogenic or endogenous hormones
      are present. Endometriosis is occasionally accompanied by malignant ovarian
      tumors, especially endometrioid and clear cell carcinomas. Its pathogenesis is
      widely debated, and its variable morphology appears to represent a continuum of
      individual presentations and progressions. Endometriosis has no pathognomonic
      signs or symptoms; it is therefore difficult to diagnose. Because of its
      enigmatic etiopathogenesis, there is currently no satisfactory therapy for all
      patients with endometriosis. Treatments include medications, surgery, or combined
      therapies; currently, the only procedures that seem to cure endometriosis are
      hysterectomy and bilateral salpingo-oophorectomy. In this paper, we review the
      most controversial and enigmatic aspects of this disease. 

PMID- 23956868
TI  - Estimation of genetic and phenotypic parameters for production traits and somatic
      cell count for jersey dairy cattle in zimbabwe.
AB  - Genetic and phenotypic parameters for production traits and somatic cell count
      (SCC) for Jersey dairy cattle in Zimbabwe were estimated. A total of 10986
      lactation records were obtained from Zimbabwe Livestock Identification Trust,
      with cows calving in the period from 1996 to 2008. An ASReml program fitting an
      animal model was used for the analyses. Heritability estimates for milk yield,
      fat yield, protein yield, fat percentage, protein percentage, and Log10SCC were
      0.30, 0.32, 0.33, 0.42, 0.44, and 0.08, respectively. The corresponding
      repeatability estimates were 0.39, 0.38, 0.39, 0.49, 0.51, and 0.16,
      respectively. The genetic and phenotypic correlations between different
      production traits ranged from -0.86 to 0.95 and from -0.88 to 0.98, respectively.
      The genetic and phenotypic correlations between production traits and Log10SCC
      were weak almost nonsignificantly differentl from zero. The results imply that
      milk traits for Jersey dairy cattle in Zimbabwe are more heritable. Therefore,
      these traits may be preferred by breeders as selection criteria for development
      of effective genetic improvement programme. 

PMID- 23956870
TI  - Predictors of postpartum glucose tolerance testing in italian women with
      gestational diabetes mellitus.
AB  - Postpartum screening is critical for early identification of type 2 diabetes in
      women previously diagnosed with gestational diabetes mellitus (GDM).
      Nevertheless, its rate remains disappointingly low. Thus, we plan to examine the
      rate of postpartum glucose tolerance test (ppOGTT) for Italian women with GDM,
      before and after counseling, and identify demographic, clinical, and/or
      biochemical predictors of adherence. With these aims, we retrospectively enrolled
      1159 women with GDM, in Calabria, Southern Italy, between 2004 and 2011. During
      the last year, verbal and written counseling on the importance of followup was
      introduced. Data were analyzed by multiple regression analysis. A significant
      increase of the return rate was observed following introduction of the counseling
      [adjusted odds ratio (AOR) 5.17 (95% CI, 3.83-6.97), P < 0.001]. Interestingly,
      previous diagnosis of polycystic ovary syndrome (PCOS) emerged as the major
      predictor of postpartum followup [AOR 5.27 (95% CI, 3.51-8.70), P < 0.001], even
      after stratification for the absence of counseling. Previous diagnosis of GDM,
      higher educational status, and insulin treatment were also relevant predictors.
      Overall, our data indicate that counseling intervention is effective, even if
      many women fail to return, whereas PCOS represents a new strong predictor of
      adherence to postpartum testing. 

PMID- 23956871
TI  - The pharmacological options in the treatment of eating disorders.
AB  - The eating disorders (DCA) are complex systemic diseases with high social impact,
      which tend to become chronic with significant medical and psychiatric
      comorbidities. The literature data showed that there is good evidence to suggest
      the use of SSRIs, particularly at high doses of fluoxetine, in the treatment of
      BN reducing both the crisis of binge that the phenomena compensates and reducing
      the episodes of binge in patients with BED in the short term. Also, the
      topiramate (an AED) showed a good effectiveness in reducing the frequency and
      magnitude of episodes of binge with body weight reduction, both in the BN that is
      in the therapy of BED. To date, modest data support the use of low doses of
      second-generation antipsychotics in an attempt to reduce the creation of
      polarized weight and body shapes, the obsessive component, and anxiety in
      patients with AN. Data in the literature on long-term drug treatment of eating
      disorders are still very modest. It is essential to remember that the
      pharmacotherapy has, however, a remarkable efficacy in treating psychiatric
      disorders that occur in comorbidity with eating disorders, such as mood
      disorders, anxiety, insomnia, and obsessive-compulsive personality disorders and
      behavior. 

PMID- 23956872
TI  - Investigating Apoptotic Effects of Methanolic Extract of Dorema glabrum Seed on
      WEHI-164 Cells.
AB  - We aimed to investigate the apoptotic effects of the methanolic extract of Dorema
      glabrum seed on WEHI-164, cancerous cells in comparison with L929, normal cells
      and compared them with the cytotoxic effects of Taxol. So, MTT test and DNA
      fragmentation assay were performed on cultured and treated cells. Also
      electrophoresis which was followed by immunoblotting was done to survey the
      production of Caspase-3 and Bcl2 proteins, and to inquire into their relative
      genes expression, RT-PCR was used. According to our findings, the methanolic
      extract of Dorema glabrum seed can alter cells morphology as they shrink and take
      a spherical shape and lose their attachment too. So, the plant extract inhibits
      cell growth albeit in a time- and dose-dependent manner and results in
      degradation of chromosomal DNA. Induction of apoptosis by the plant extract was
      proved by the reduction of pro-Caspase-3 and Bcl2 proteins and increase in
      Caspase-3 gene expression and decrease in that of bcl2 too. Our data well
      established the antiproliferative effect of methanolic extract of Dorema glabrum
      seed and clearly showed that the plant extract can induce apoptosis and not
      necrosis in vitro. These results demonstrated that Dorema glabrum seed might be a
      novel and attractive therapeutic candidate for tumor treatment. 

PMID- 23956873
TI  - Evaluation of 10-year experience of Wegener's granulomatosis in Iranian children.
AB  - Wegener's granulomatosis or granulomatosis polyangiitis (GPA) is an uncommon
      chronic systemic vasculitis in children. The aim of this study was to describe
      pediatric patients with GPA in Iran. We studied records of all patients with GPA
      diagnosis who were referred to all Iranian Pediatric Rheumatology Division from
      2002 to 2011. A total of 11 patients (5 females and 6 males) enrolled in this
      study. In children less than 15 years old, the prevalence of GPA is 0.6 per
      million. The mean age of GPA diagnosis was 11 years and average delay diagnosis
      was 20 months. Mortality rate was 18.1% due to pulmonary vasculitis and
      infection. The most common organ system involvement was upper and lower
      respiratory tract involvement (81.8% and 63.9%, resp.). Other common
      manifestations were renal (36.3), skin (27.2%), and eye involvement (18.2%). 

PMID- 23956869
TI  - Clinical presentation, pathogenesis, diagnosis, and treatment of epidermolysis
      bullosa acquisita.
AB  - Epidermolysis bullosa acquisita (EBA) is a chronic mucocutaneous autoimmune skin
      blistering disease. The pathogenic relevance of autoantibodies targeting type VII
      collagen (COL7) has been well-documented. Therefore, EBA is a prototypical
      autoimmune disease with a well-characterized pathogenic relevance of autoantibody
      binding to the target antigen. EBA is a rare disease with an incidence of 0.2 new
      cases per million and per year. The current treatment of EBA relies on general
      immunosuppressive therapy, which does not lead to remission in all cases.
      Therefore, there is a high, so far unmet medical need for the development of
      novel therapeutic options. During the last 10 years, several novel in vitro and
      in vivo models of EBA have been established. These models demonstrated a critical
      role of the genetic background, T cells, and cytokines for mediating the loss of
      tolerance towards COL7. Neutrophils, complement activation, Fc gamma receptor
      engagement, cytokines, several molecules involved in cell signaling, release of
      reactive oxygen species, and matrix metalloproteinases are crucial for
      autoantibody-induced tissue injury in EBA. Based on this growing understanding of
      the diseases' pathogenesis, several potential novel therapeutic targets have
      emerged. In this review, the clinical presentation, pathogenesis, diagnosis, and
      current treatment options for EBA are discussed in detail. 

PMID- 23956874
TI  - Assessing Depression among Older Persons with Arthritis: A Nationwide Health
      Status Survey.
AB  - Objectives. This study aimed to assess the health status of a nationwide sample
      of elderly persons having arthritis and determine the prevalence of depressive
      symptomatology in this population. Methods. WebTV technology was utilized to
      administer health status and depression surveys to a nationally representative
      sample of 550 randomly selected older persons. Predetermined cutoff scores on
      Short Form-36 (SF-36) scale and Center for Epidemiological Scale for Depression
      (CES-D) were used to identify individuals with depressive mood. Results. Sixteen
      percent (n = 76) of the respondents were found to be at risk for depression. Key
      associations among health domains of SF-36 and CES-D variables were statistically
      significant and were in the expected direction. Discussion. The risk of
      depression among older adults who have arthritis is moderate. A significant
      decline in multiple domains of health of older persons is likely when depression
      coexists with arthritis. Early screening for depressive symptomatology and prompt
      treatment should be an essential part of arthritis management in primary care
      practice. 

PMID- 23956875
TI  - Implementation Interventions Used in Nursing Homes and Hospitals: A Descriptive,
      Comparative Study between Austria, Germany, and The Netherlands.
AB  - Translating guidelines into nursing practice remains a considerable challenge.
      Until now, little attention has been paid to which interventions are used in
      practice to implement guidelines on changing clinical nursing practice. This
      cross-sectional study determined the current ranges and rates of implementation
      related interventions in Austria, Germany, and The Netherlands and explored
      possible differences between these countries. An online questionnaire based on
      the conceptual framework of implementation interventions (professional,
      organizational, financial, and regulatory) from the Cochrane Effective Practice
      and Organization of Care (EPOC) data collection checklist was used to gather data
      from nursing homes and hospitals. Provision of written materials is the most
      frequently used professional implementation intervention (85%), whereas changes
      in the patient record system rank foremost among organisational interventions
      (78%). Financial incentives for nurses are rarely used. More interventions were
      used in Austria and Germany than in The Netherlands (20.3/20.2/17.3).
      Professional interventions are used more frequently in Germany and financial
      interventions more frequently in The Netherlands. Implementation efforts focus
      mainly on professional and organisational interventions. Nurse managers and other
      responsible personnel should direct their focus to a broader array of
      implementation interventions using the four different categories of EPOC's
      conceptual framework. 

PMID- 23956876
TI  - Motor Skill Training Promotes Sensorimotor Recovery and Increases Microtubule
      Associated Protein-2 (MAP-2) Immunoreactivity in the Motor Cortex after
      Intracerebral Hemorrhage in the Rat.
AB  - Motor skill learning may induce behavioral and neurophysiological adaptations
      after intracerebral hemorrhage (ICH). Learning a new motor skill is associated
      with dendritic reorganization and requires protein synthesis and expression of
      MAP-2. The purpose of this study was to evaluate motor performance and expression
      of MAP-2 in the motor cortex of rats submitted to intracerebral hemorrhage model
      (ICH) and skill task training (SK) or unskilled training (US) during 4 weeks. The
      Staircase test was used for behavioral evaluation, and relative optical densities
      and morphometrical analysis were used to estimate MAP-2 immunoreactivity and
      parameters of brain tissue in both motor cortices. Results show that skill task
      training performed with the impaired forelimb was able to increase MAP-2
      immunoreactivity in the motor cortex either in sham or in ICH groups in both
      cortices: ipsilesional [F (5,35) = 14.25 (P < 0.01)] and contralesional
      hemispheres [F (5,35) = 9.70 (P < 0.01)]. ICH alone also increased MAP-2
      immunoreactivity despite the absence of functional gains. Behavioral evaluation
      revealed that ICH-SK group performed better than ICH and ICH-US animals in the
      Staircase test. Data suggest that motor skill training induces plastic
      modifications in both motor cortices, either in physiological or pathological
      conditions and that skill motor training produces higher brain plasticity and
      positive functional outcomes than unskilled training after experimental
      intracerebral hemorrhage. 

PMID- 23956877
TI  - Alcohol-attributable fraction of ischemic heart disease mortality in Russia.
AB  - Objective. The aim of the present study was to estimate the premature ischemic
      heart disease (IHD) mortality attributable to alcohol abuse in Russia on the
      basis of aggregate-level data of mortality and alcohol consumption. Method. Age
      standardized sex-specific male and female IHD mortality data for the period 1980
      2005 and data on overall alcohol consumption were analyzed by means of
      autoregressive integrated moving average (ARIMA) time series analysis. Results.
      The results of the analysis suggest that 41.1% of all male deaths and 30.7% of
      female deaths from IHD in Russia could be attributed to alcohol. The estimated
      alcohol-attributable fraction for men ranged from 24.0% (75+ age group) to 62.0%
      (15-29 age group) and for women from 20.0% (75+ age group) to 64.0% (30-44 age
      group). Conclusions. The outcomes of this study provide indirect support for the
      hypothesis that the high rate of IHD mortality in Russia may be related to
      alcohol, as indicated by a close aggregate-level association between number of
      deaths from IHD and overall alcohol consumption per capita. 

PMID- 23956879
TI  - Interferon Inducible IFI16 Expression in p16 Positive Squamous Cell Carcinoma of
      the Oropharynx.
AB  - Human-papillomavirus- (HPV-) positive oropharyngeal squamous cell carcinomas
      (OPSCC) are reported to be more responsive to treatment and to be related to a
      favorable prognosis compared with non-HPV carcinomas. However, the molecular
      basis of the responsiveness is unclear. Interferon inducible IFI16, which is
      implicated in the control of cell growth, apoptosis, angiogenesis, and
      immunomodulation in various types of cancers, is reported to be frequently
      expressed in the HPV-positive head and neck SCC and to correlate with a better
      prognosis. In this study, we hypothesized that HPV related OPSCC expresses IFI16
      resulting in favorable prognosis. To clarify the relationship between the
      prognosis of HPV related OPSCC patients and IFI16 status, we examined
      immunohistologically the pretreatment specimens of OPSCC for the expression of
      p16 as a surrogate marker of HPV infection and IFI16. We could not show that the
      expression of IFI16 is associated with that of p16. There was no significant
      difference in the survival rate between IFI16 positive and negative groups.
      Patients with p16 negative tumor exhibited worse survival rate regardless of
      IFI16 status. In this limited case series, we could not conclude that IFI16
      expression is altered in p16 positive OPSCC and that it would be a new predictive
      marker or a useful therapeutic tool. 

PMID- 23956878
TI  - Association of oral health and cardiovascular disease risk factors "results from
      a community based study on 5900 adult subjects".
AB  - Objectives. This study aimed to determine the association between some oral
      health status as a risk factor for cardiac diseases and other cardiovascular
      disease (CVD) risk factors in a sample of Iranian population in 2011. Methods.
      The study recruited 5900 inhabitants who aged 15-75 years old of Kerman city
      through a population based cluster sampling. Having collected informed consent,
      participants were interviewed for CVD risk factors. Some oral health indicators
      such as DMFT, Gingival Inflammation index, and Community Periodontal Index were
      assessed. The association between oral health indices and CVD risk factors was
      tested using multivariate regression models. Results. The mean age of
      participants was 33.5 years, and 45.1% were male. Moderate gingival inflammation
      was observed in 67.6% of participants. Presence of sub- or supragingival calculus
      was more common (90%) in participants. Older age (RR from 2.7 to 3.88), cigarette
      smoking (RR = 1.49), and high blood glucose (RR = 1.41) showed an increased risk
      for oral diseases after adjustment for different covariates including established
      CVD risk factors. Conclusion. The study results showed an increase in periodontal
      diseases in the presence of some CVD risk factors. Therefore there may be a
      bilateral but independent association for both conditions and common risk factor
      approach preventive program is highly recommended. 

PMID- 23956880
TI  - Radical Cystectomy after BCG Immunotherapy for High-Risk Nonmuscle-Invasive
      Bladder Cancer in Patients with Previous Prostate Radiotherapy.
AB  - Purpose. Intravesical Bacillus Calmette-Guerin (BCG) immunotherapy is indicated
      for high-grade nonmuscle-invasive bladder cancer (NMIBC). The efficacy of BCG in
      patients with a history of previous pelvic radiotherapy (RT) may be diminished.
      We evaluated the outcomes of radical cystectomy for BCG-treated recurrent bladder
      cancer in patients with a history of RT for prostate cancer (PC). Methods. A
      retrospective chart review was performed to identify patients with primary NMIBC.
      We compared the outcomes of three groups of patients who underwent radical
      cystectomy for BCG-refractory NMIBC: those with a history of RT for PC, those who
      previously underwent radical prostatectomy (RP), and a cohort without PC or RT
      exposure. Results. From 1996 to 2008, 53 patients underwent radical cystectomy
      for recurrent NMIBC despite BCG. Those with previous pelvic RT were more likely
      to have a higher pathologic stage and decreased recurrence-free survival compared
      to the groups without prior RT exposure. Conclusion. Response rates for
      intravesical BCG therapy may be impaired in those with prior prostate
      radiotherapy. Patients with a history of RT who undergo radical cystectomy after
      failed BCG are more likely to be pathologically upstaged and have decreased
      recurrence-free survival. Earlier consideration of radical cystectomy may be
      warranted for those with NMIBC who previously received RT for PC. 

PMID- 23956881
TI  - Formulation development and evaluation of fast disintegrating tablets of
      salbutamol sulphate for respiratory disorders.
AB  - Recent developments in fast disintegrating tablets have brought convenience in
      dosing to pediatric and elderly patients who have trouble in swallowing tablets.
      The objective of the present study was to prepare the fast disintegrating tablet
      of salbutamol sulphate for respiratory disorders for pediatrics. As precision of
      dosing and patient's compliance become important prerequisites for a long-term
      treatment, there is a need to develop a formulation for this drug which overcomes
      problems such as difficulty in swallowing, inconvenience in administration while
      travelling, and patient's acceptability. Hence, the present investigation were
      undertaken with a view to develop a fast disintegrating tablet of salbutamol
      sulphate which offers a new range of products having desired characteristics and
      intended benefits. Superdisintegrants such as sodium starch glycolate was
      optimized. Different binders were optimized along with optimized
      superdisintegrant concentration. The tablets were prepared by direct compression
      technique. The tablets were evaluated for hardness, friability, weight variation,
      wetting time, disintegration time, and uniformity of content. Optimized
      formulation was evaluated by in vitro dissolution test, drug-excipient
      compatibility, and accelerated stability study. It was concluded that fast
      disintegrating tablets of salbutamol sulphate were formulated successfully with
      desired characteristics which disintegrated rapidly; provided rapid onset of
      action; and enhanced the patient convenience and compliance. 

PMID- 23956882
TI  - Impact of amending the acetylcysteine marketing authorisation on treatment of
      paracetamol overdose.
AB  - In September 2012, the Medicines and Healthcare products Regulatory Agency (MHRA)
      substantially amended the Marketing Authorisation for acetylcysteine following an
      extensive review. The present study examined the impact of this license change on
      patterns of acetylcysteine use in patients presenting to hospital after
      paracetamol (acetaminophen) overdose. Between September 2011 and April 2013, 785
      consecutive patients presented to York Hospital due to paracetamol overdose, and
      a before-after analysis was used to compare outcomes. There were 483 patients
      before and 302 patients after the license amendment, and age, gender, acute or
      staggered overdose pattern, and dose were similar in both groups. In the patients
      with paracetamol concentrations between the "100-line" and "200-line," a
      significantly higher proportion received acetylcysteine treatment (51% before
      versus 98% after, P = 0.0029), as expected. A modest increase was also observed
      in relation to late or staggered overdose or cases where the time of ingestion
      was uncertain (53% versus 74%, P = 0.0430). The median duration of hospital stay
      increased across the entire study population, from 15 to 24 hours (P = 0.0159)
      due to the increased proportion of patients requiring acetylcysteine treatment.
      The findings indicate that the MHRA amendment is a financially costly
      intervention, and further studies are needed to examine clinical outcomes so that
      its cost effectiveness might be addressed. 

PMID- 23956883
TI  - Open Tracheostomy after Aborted Percutaneous Approach due to Tracheoscopy
      Revealing Occult Tracheal Wall Ulcer.
AB  - Tracheostomy is a common procedure for intensive care patients requiring
      prolonged mechanical ventilation. In this case report, we describe a 78-year-old
      female patient admitted for an aneurysm of the cerebral anterior communicating
      artery. Following immediate endovascular coiling, she remained ventilated and was
      transferred to the neurological intensive care unit. On postoperative day ten, a
      percutaneous tracheostomy (PCT) was requested; however, a large ulcer or possible
      tracheoesophageal fistula was identified on the posterior tracheal wall following
      bronchoscopic assessment of the trachea. Therefore, the requested PCT procedure
      was aborted. An open tracheostomy in the operating room was completed; however,
      due to the position and depth of the ulcer, a reinforced endotracheal tube (ETT)
      was placed via the tracheostomy. Four days later, the reinforced ETT was replaced
      with a Shiley distal extended tracheostomy tube to bypass the ulceration. Careful
      inspection and evaluation of the tracheostomy site before PCT prevented a
      potentially life-threatening issue in our patient. 

PMID- 23956884
TI  - The Hybrid Aesthetic Functional (HAF) Appliance: A Less Visible Proposal for
      Functional Orthodontics.
AB  - In modern orthodontics, aesthetics appear to have a decisive influence on
      orthodontic appliance preferences and acceptability. This paper reports the early
      application of a newly emerged functional device with enhanced aesthetics in a
      Class II treatment. Patient perspectives and technical considerations are
      discussed along with recommendations for further design development. It can be
      assumed that the use of thermoplastic material-based appliances may meet both the
      therapeutic and aesthetic demands of young age groups. 

PMID- 23956885
TI  - Supraorbital blowin fracture presenting as an ocular dystopia in a nine-year-old
      girl.
AB  - A 9-year-old girl was referred to a trauma centre with severe head injury. 3D CT
      scan revealed depressed fracture involving the frontal bone on the right side,
      right parietal bone, and right superior orbital margin, right lamina papyracea.
      The frontal table was managed conservatively and open reduction and internal
      fixation was done for the supraorbital blow in to correct the ocular dystopia.
      The clinical course, possible mechanism, and management of the patient are
      discussed. 

PMID- 23956886
TI  - Acute myocardial infarction and massive pulmonary embolus presenting as cardiac
      arrest: initial rhythm as a diagnostic clue.
AB  - Myocardial infarction (MI) and massive pulmonary embolism (MPE) are common causes
      of cardiac arrest. We present two cases with similar clinical presentation and
      EKG findings but different initial rhythms. Case  1. A 55-year-old African
      American male (AAM) was brought to the emergency room (ER) with cardiac arrest
      and pulseless electrical activity (PEA). Twelve-lead electrocardiogram (EKG) was
      suggestive of ST segment elevations (STEs) in anterolateral leads. Coronary
      angiogram did not reveal any significant obstruction. An echocardiogram was
      suggestive of a pulmonary embolus (PE). Autopsy revealed a saddle PE. Case  2. A
      45-year-old AAM with a history of coronary artery disease was brought to the ER
      after ventricular fibrillation (VF) arrest. Twelve-lead EKG was suggestive of STE
      in anterior leads. Coronary angiogram revealed in-stent thrombosis. In cardiac
      arrests, distinguishing the two major etiologies (MI and MPE) can be challenging.
      PEA is more commonly associated with MPE versus MI due to near complete
      obstruction of pulmonary blood flow with an intact electrical conduction system.
      MI is more commonly associated with VF as the electrical conduction system is
      affected more often by ischemia. In conclusion, the previous cases illustrate
      that initial rhythm may be a vital diagnostic clue. 

PMID- 23956887
TI  - Novel onset of a posttraumatic superficial temporal artery pseudoaneurysm.
AB  - Less than 200 cases of posttraumatic superficial temporal artery pseudoaneurysm
      have been described in the literature. The majority of these cases result from
      blunt head trauma and are diagnosed an average of three weeks following the
      inciting traumatic event. In this case report, we describe a superficial temporal
      artery pseudoaneurysm that developed and was diagnosed the same day of a blunt
      head trauma in a 54-year-old white male. This is the earliest formation/diagnosis
      of post-traumatic superficial temporal artery pseudoaneurysm yet reported in the
      literature. This case report demonstrates that this diagnosis should be kept in
      the list of differential diagnoses for a post-traumatic soft tissue mass of the
      face, even immediately following the traumatic event. 

PMID- 23956888
TI  - A rare cause for acute chest pain in the emergency setting that is hard to
      swallow.
AB  - Intramural esophageal hematoma is a very rare but important cause of chest pain.
      This condition shares similarity with the diagnosis of other thoracic emergencies
      and has a high potential for misdiagnosis. The emergency clinician plays a
      critical role in the early identification and management of these patients. The
      management of intramural hematomas is typically conservative, and a misdiagnosis
      could lead to deleterious effects. Preexisting coagulopathy is one of the major
      risk factors. With the advent of new anticoagulation medications to prevent
      thromboembolic events, it is important that emergency medicine providers expand
      the differential diagnosis of chest pain. 

PMID- 23956889
TI  - Postpolypectomy electrocoagulation syndrome: a mimicker of colonic perforation.
AB  - Postpolypectomy electrocoagulation syndrome is a rare complication of polypectomy
      with electrocautery and is characterized by a transmural burn of the colon wall.
      Patients typically present within 12 hours after the procedure with symptoms
      mimicking colonic perforation. Presented is the case of a 56-year-old man who
      developed abdominal pain six hours after colonoscopy during which polypectomy was
      performed using snare cautery. CT imaging of the abdomen revealed circumferential
      thickening of the wall of the transverse colon without evidence of free air. The
      patient was treated conservatively as an outpatient and had resolution of his
      pain over the following four days. Recognition of the diagnosis and understanding
      of the treatment are important to avoid unnecessary exploratory laparotomy or
      hospitalization. 

PMID- 23956890
TI  - Acute Stridor and Respiratory Failure due to Retrosternal Subglottic Stenosis of
      Unknown Origin.
AB  - Respiratory failure due to subglottic stenosis is a rare but serious condition. A
      22-year-old male presented to the emergency department (ED) with shortness of
      breath, stridor, and change in tone of voice. The patient did not complain of B
      symptoms (fever, weight loss, and night sweats). In the week before this
      presentation, he was diagnosed with an upper respiratory tract infection with
      associated bronchospasm and discharged on oral antibiotics and inhaled salbutamol
      without effect. He developed hypercapnic respiratory failure in the ED after a
      coughing episode. A normal nasopharyngoscopic examination and a subtle
      mediastinal abnormality on chest radiograph lead to a working diagnosis of
      retrosternal subglottic obstruction. The complexities of his airway management
      and suggestions for multidisciplinary approach are discussed. 

PMID- 23956891
TI  - Erratum to "hypogonadotropic hypogonadism associated with hereditary hemorrhagic
      telangiectasia".

PMID- 23956892
TI  - Patent foramen ovale in patients with sickle cell disease and stroke: case
      presentations and review of the literature.
AB  - Although individuals with sickle cell disease (SCD) are at increased risk for
      stroke, the underlying pathophysiology is incompletely understood. Intracardiac
      shunting via a patent foramen ovale (PFO) is associated with cryptogenic stroke
      in individuals without SCD. Recent evidence suggests that PFOs are associated
      with stroke in children with SCD, although the role of PFOs in adults with stroke
      and SCD is unknown. Here, we report 2 young adults with SCD, stroke, and PFOs.
      The first patient had hemoglobin SC and presented with a transient ischemic
      attack and a subsequent ischemic stroke. There was no evidence of cerebral
      vascular disease on imaging studies and the PFO was closed. The second patient
      had hemoglobin SS and two acute ischemic strokes. She had cerebral vascular
      disease with moyamoya in addition to a peripheral deep venous thrombosis (DVT).
      Chronic transfusion therapy was recommended, and the DVT was managed with
      warfarin. The PFO was not closed, and the patients' neurologic symptoms were
      stabilized. We review the literature on PFOs and stroke in SCD. Our cases and the
      literature review illustrate the dire need for further research to evaluate PFO
      as a potential risk factor for stroke in adults with SCD. 

PMID- 23956893
TI  - Early Complete Molecular Response to First-Line Nilotinib in Two Patients with
      Chronic Myeloid Leukemia Carrying the p230 Transcript.
AB  - Chronic myeloid leukemia (CML) with the rare fusion gene e19a2, encoding a p230
      protein, has been described in patients with typical or rather aggressive
      clinical course. Although tyrosine kinase inhibitors (TKIs) induce a substantial
      cytogenetic and molecular response in all phases of CML, a minority of p230
      positive patients have been treated with TKIs. We report two cases of CML
      patients carrying the p230 transcript, who achieved fast and deep complete
      molecular response (CMR) after frontline treatment with nilotinib. Our results
      suggest the use of nilotinib as frontline agent for the treatment of this CML
      variant. 

PMID- 23956894
TI  - Subdural and cerebellar hematomas which developed after spinal surgery: a case
      report and review of the literature.
AB  - Cerebellar hemorrhage following a spinal surgery is extremely rare; however,
      considering the localization, it can cause major clinical manifestations. While
      it is considered that these types of bleedings occur secondary to a venous
      infarct, the pathogenesis is still unclear. A 57-year-old male patient who
      underwent a laminectomy by exposing T12-L5 and had pedicle screws placed for
      ankylosing spondylitis developed a CSF leak due to a 2 mm dural tear. A
      hemorrhage with parallel streaks on the left cerebellar hemisphere was seen in CT
      scan, and a thin subdural hematoma at right frontotemporal region was seen on
      cranial MRI, performed after the patient developed intense headache, nausea,
      vomiting, and stiff neck in the early postoperative period. In this paper, a case
      of cerebellar and subdural hematomas following a spinal surgery is discussed with
      its clinical and radiologic findings. 

PMID- 23956895
TI  - Incarcerated Trocar Site Herniation of the Small Bowel following Laparoscopic
      Myomectomy.
AB  - Small bowel herniation through the fascial defect created by the entry of trocars
      is one of the major complications of the laparoscopic surgery. In this paper, we
      describe a 42-year-old woman developing an incarcerated trocar site herniation of
      the small bowel following laparoscopic myomectomy and treated by laparoscopic
      approach. 

PMID- 23956896
TI  - Abscessed uterine and extrauterine adenomyomas with uterus-like features in a 56
      year-old woman.
AB  - Adenomyosis, also known as endometriosis interna, is the presence of endometrial
      glands and stroma within the myometrium. Its localised form is called adenomyoma
      and mimics a leiomyoma. Rarely, adenomyomas are located outside the uterus and
      some of them form uterus-like masses with a thick muscle wall and an endometrium
      lined central cavity. They are generally located in the ovary or broad ligament,
      and, although they are closely related to endometriosis, their pathogenetic
      mechanisms are different from each other. Mullerian duct fusion defect and
      subcoelomic mesenchyme transformation theory are two possible pathogenetic
      mechanisms for this rare entity. Here we report abscessed uterine and
      extrauterine adenomyomas forming uterus-like masses in the left and right broad
      ligament and an ectopic adrenal tissue in the left paraovarian region in a 56
      year-old woman. Although there is a reported abscessed adenomyosis in the
      literature, this is the first abscessed extrauterine uterus-like masses with
      synchronous pelvic pathologies like endometriosis, leiomyomas, adenomyosis, an
      endometrial polyp, an endocervical polyp, and an ectopic adrenal tissue. This
      benign lesion gives the impression of leiomyoma, a uterine malformation, or even
      malignancy preoperatively. Frozen section helps in differential diagnosis. 

PMID- 23956897
TI  - Benign metastatic leiomyoma presenting as a hemothorax.
AB  - Uterine leiomyomas have been reported to metastasize to various organs including
      the lungs, skeletal muscles, bone marrow, peritoneum, and heart. They may present
      with symptoms related to the metastases several years after hysterectomy. These
      tumors regress after menopause, and it is rare to detect active tumors in
      postmenopausal women. Despite their ability to metastasize, they are considered
      to be benign due to the lack of anaplasia. Pulmonary benign metastasizing
      leiomyoma is usually detected in the form of pulmonary nodules incidentally on
      imaging. Tissue biopsy of these nodules is required to identify them as benign
      metastasizing leiomyomas. Immunohistochemical analysis and molecular profiling
      may further help detect any malignant transformation in it. Untreated pulmonary
      benign metastasizing leiomyoma may result in the formation of cystic structures,
      destruction of lung parenchyma, and hemothorax and may cause respiratory failure.
      Surgical resection and hormonal therapy help prevent progression of this disease
      and provide an avenue for a cure. 

PMID- 23956898
TI  - Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long
      Term Bisphosphonate Use in Breast Cancer.
AB  - Bisphosphonates are widely used in the treatment of breast cancer with bone
      metastases. We report a case of a female with breast cancer presented with a rash
      around a previous mastectomy site and a discharge lesion on her right chest wall
      in August 2010. Biopsy of the lesion showed dystrophic calcification and
      metaplastic bone formation. The patient's history revealed a long term use of
      zoledronic acid for the treatment of breast cancer with bone metastasis. We
      stopped the treatment since we believed that the cutaneous dystrophic
      calcification could be associated with her long term bisphosphonate therapy.
      Adverse cutaneous events with bisphosphonates are very rare, and dystrophic
      calcification has not been reported previously. The dystrophic calcification and
      metaplastic bone formation in this patient are thought to be due to long term
      bisphosphonate usage. 

PMID- 23956899
TI  - Adenocarcinoma of the right breast in a man with intellectual disability.
AB  - A 64-year-old man with moderate intellectual disability developed a large right
      breast carcinoma with lymph node metastases. Cancer treatment is often difficult
      in persons with intellectual disability. However, the patient could be treated
      according to the current protocols with surgery, chemotherapy, and radiotherapy.
      He is alive and in good health two years after discovery of his tumor. Although
      breast cancer is estimated as frequent in women with intellectual disability as
      it is in nondisabled women, our patient is the second man with intellectual
      disability reported with a breast carcinoma. 

PMID- 23956900
TI  - A minor modification of direct browplasty technique in a patient with brow ptosis
      secondary to facial paralysis: copy-paste-excise and stitch.
AB  - Purpose. This report aimed to describe a minor modification of the traditional
      direct browplasty technique that aids in surgical planning for patients with brow
      ptosis secondary to facial paralysis without changing the shape of the brow. Case
      Report. A 74-year-old male patient with left facial paralysis secondary to
      chronic otitis media was referred with a complaint of low vision due to brow
      ptosis. We performed direct browplasty with a minor modification in order to aid
      a treatment customized to the patient. In this technique, a transparent film
      paper is used to copy the brow shape. A brow-shaped excision is facilitated just
      superior to the ptotic brow. Conclusion. The authors found that the copy-paste
      excise and stitch technique was effective and successful for deciding the shape
      and the amount of excision that should be performed in patients with brow ptosis
      without resulting in asymmetrical, arched, and feminized brows. 

PMID- 23956901
TI  - Treatment of Renal Cell Carcinoma with 2-Stage Total en bloc Spondylectomy after
      Marked Response to Molecular Target Drugs.
AB  - Metastatic renal cell carcinoma of the bone occurs at a high rate, and the
      prognosis is poor. In general, total en bloc spondylectomy is considered when
      there is only one vertebral metastasis and the primary disease is treated.
      However, palliative surgery is selected when the primary disease is not being
      treated or metastasis occurs to an important organ. We encountered a patient in
      whom lung and vertebra metastases were already present at the time of the first
      examination at our department and the prognosis was considered poor. However,
      molecular targeted therapy was markedly effective and enabled 2-stage total en
      bloc spondylectomy. As of one year after total en bloc spondylectomy, the
      condition has improved to cane gait, and surgery for lung metastasis is planned.
      Molecular target drugs might markedly change the current therapeutic strategy for
      renal cell carcinoma. 

PMID- 23956902
TI  - Hypersensitivity to suture anchors.
AB  - Hypersensitivity to suture anchor is extremely rare. Herein, we present a case in
      which hypersensitivity to suture anchor was strongly suspected. The right rotator
      cuff of a 50-year-old woman was repaired with a metal suture anchor. Three weeks
      after the surgery, she developed erythema around her face, trunk, and hands,
      accompanied by itching. Infection was unlikely because no abnormalities were
      detected by blood testing or by medical examination. Suspicious of a metallic
      allergy, a dermatologist performed a patch testing 6 months after the first
      surgery. The patient had negative reactions to tests for titanium, aluminum, and
      vanadium, which were the principal components of the suture anchor. The anchor
      was removed 7 months after the first surgery, and the erythema disappeared
      immediately. When allergic symptoms occur and persist after the use of a metal
      anchor, removal should be considered as a treatment option even if the patch test
      result is negative. 

PMID- 23956903
TI  - Nonoperative treatment of distal biceps brachii musculotendinous partial rupture:
      a report of two cases.
AB  - Musculotendinous ruptures of the distal biceps brachii are extremely rare
      injuries whose clinical presentation is similar to distal biceps avulsion. We
      describe two cases of patients who suffered a distal biceps brachii
      musculotendinous partial rupture. The first patient was playing soccer as
      goalkeeper and experienced sudden pain while throwing the ball overhead with his
      left arm. The second patient experienced sudden pain while weightlifting with his
      right arm. The mechanism of injury was the same in the two cases, as both
      involved glenohumeral elevation with elbow extension and forearm supination.
      Neither of these two patients underwent surgical repair or rehabilitation, and
      both had perfect scores of 100 on the Mayo Clinic Performance Index for the Elbow
      at one-year followup. 

PMID- 23956904
TI  - Papillary Thyroid Carcinoma in a Branchial Cleft Cyst without a Thyroid Primary:
      Navigating a Diagnostic Dilemma.
AB  - We report a rare case of papillary thyroid carcinoma incidentally found within a
      branchial cleft cyst. Only four other cases have been described in the
      literature. A total thyroidectomy and selective neck dissection was performed,
      and no evidence of occult primary disease was found after review of fine
      sections. Branchial cleft cysts are the most common lateral neck masses. Ectopic
      thyroid tissue within a branchial cleft cyst is an unusual phenomenon, and
      papillary thyroid carcinoma arising from this tissue is extremely rare.
      Clinicians are left with a diagnostic dilemma when presented with thyroid tissue
      neoplasm within a neck cyst in the absence of a thyroid primary-is this a case of
      metastatic disease with a missed primary or rather carcinoma arising in ectopic
      thyroid tissue? A thorough discussion of the etiologies of these lateral neck
      masses is reviewed including the embryogenesis of thyroid tissue in a branchial
      cleft cyst. The prognosis of patients with papillary thyroid carcinoma in lateral
      neck cysts without a primary site identified appears to be good following
      excision of the cyst and total thyroidectomy. Other management recommendations
      regarding these unique lateral neck malignancies are also presented. 

PMID- 23956905
TI  - Retropharyngeal calcific tendonitis mimics a retropharyngeal abscess.
AB  - Retropharyngeal calcific tendonitis (RCT) is an uncommon, self-limiting condition
      that is often omitted in the differential diagnosis of a retropharyngeal fluid
      collection. This condition mimics a retropharyngeal abscess and should be
      considered when evaluating a fluid collection in the retropharyngeal space.
      Although calcific tendonitis at other sites has been well described in the
      medical literature, it appears that this entity has been underreported in the
      otolaryngology literature where only a few case reports have been identified.
      Presumably, the actual incidence is higher than the reported incidence, due to
      lack of familiarity with this disorder. As an otolaryngologist's scope of
      practice includes the managements of retropharyngeal lesions, it is important for
      the otolaryngologist to recognize the presentation of acute RCT and be familiar
      with appropriate treatment strategies. Retropharyngeal calcific tendonitis
      presents with neck pain, limitation of neck range of motion and includes
      inflammation, calcifications, and a sterile effusion within the longus colli
      muscle. Treatment is medical with nonsteroidal anti-inflammatory medications. RCT
      does not require surgical treatment, and an accurate diagnosis can prevent
      unnecessary attempts at operative drainage. In this study, we discuss two cases
      of RCT, summarize the salient features in diagnosis, including key radiologic
      features, discuss treatment options, and review the literature. 

PMID- 23956906
TI  - Extensive tympanic membrane cholesteatoma with marginal perforation: an unusual
      case.
AB  - The migration of squamous epithelium of external ear through a tympanic membrane
      perforation into the middle ear forms a cholesteatoma. But it is extremely a rare
      condition to observe extensive cholesteatoma on the medial surface of tympanic
      membrane with perforation. This condition is termed tympanic membrane
      cholesteatoma (TMC). We herein present an exceptional case of extensive TMC with
      marginal perforation. 

PMID- 23956907
TI  - Predictive factors of potential malignant transformation in recurrent calcifying
      cystic odontogenic tumor: review of the literature.
AB  - Calcifying cystic odontogenic tumor (CCOT) demonstrates considerable diversity in
      histopathology and clinical behavior. Ghost cell odontogenic carcinoma (GCOC) is
      the rare malignant counterpart of CCOT and it frequently arises from malignant
      transformation of a recurrent CCOT. In this paper, we present a case of CCOT and
      discuss its distinct histopathologic features in recurrence. Then, we will have a
      review on clinical, histopathological, and immunohistochemical aspects of GCOC in
      the literature. Predictive factors of malignant transformation in a benign CCOT
      will also be discussed. 

PMID- 23956908
TI  - Physiological striae atrophicae of adolescence with involvement of the upper
      back.
AB  - We report a 13-year-old boy with multiple purplish, atrophic, horizontal linear
      striae in the thoracic area. He reported a growth spurt in the preceding 12
      months. His past health was unremarkable, and he took no medications. To our
      knowledge, physiological striae atrophicae of adolescence where idiopathic striae
      were restricted to the upper back have rarely been reported. Physiological striae
      atrophicae of adolescence may, on occasions, be mistaken for child abuse. It is
      important that child care professionals recognize this condition so that false
      accusations of child abuse will not be made. 

PMID- 23956909
TI  - Pneumococcal meningitis in an adolescent with fever and foot ache.
AB  - Invasive pneumococcal disease predominantly affects younger children, elderly,
      and immunocompromised patients. Pneumococcal meningitis is a particularly
      important form of presentation, considering its high rate of morbimortality. We
      present the case of a previously healthy 12-year-old adolescent male who was
      hospitalized due to suspicion of osteoarticular infection in his left foot. A few
      hours later, he developed meningeal signs, exhibiting slight pleocytosis and
      Streptococcus pneumoniae isolates in both cerebrospinal fluid and blood. Imaging
      studies were inconclusive regarding the nature of the foot disorder. We
      considered the hypothesis of osteomyelitis of the navicular bone as the most
      likely, for which he completed six weeks of antibiotic therapy. There was a
      favorable clinical evolution, along with complete absence of osteoarticular or
      neurological sequelae. The relevance of this clinical case resides in the unusual
      presentation of invasive pneumococcal disease in this age group, as well as in
      the rare form of orthopedic involvement. 

PMID- 23956910
TI  - Two neonates with congenital hydrocolpos.
AB  - Introduction. Neonatal hydrocolpos is a rare condition. Hydrocolpos is cystic
      dilatation of the vagina with fluid accumulation due to a combination of
      stimulation of secretary glands of the reproductive tract and vaginal
      obstruction. The differential for a neonatal presentation of lower abdominal mass
      includes urogenital anomalies, Hirschsprung's, disease or sacrococcygeal
      teratoma. Prenatal diagnosis and early newborn imaging studies leads to early
      detection and treatment of these cases. Case. We report here two cases of
      neonatal hydrocolpos with prenatal diagnosis of lower abdominal mass.
      Postnatally, ultrasound, MRI imaging, and cystoscopy confirmed large cystic mass
      as hydrocolpos with distal vaginal obstruction. Both patients had enlarged renal
      system secondary to mass effect. Conclusion. High index of suspicion for
      hydrocolpos in a newborn presenting with fetal diagnosis of infraumbilical
      abdominal mass will facilitate timely intervention and prevention of
      complications. 

PMID- 23956911
TI  - A case of bipolar affective disorder and aspiration pneumonia.
AB  - Adults with mental illness are at a higher risk of aspiration pneumonia than the
      general population. We describe the case of a patient with bipolar affective
      disorder and two separate episodes of aspiration pneumonia associated with acute
      mania. We propose that he had multiple predisposing factors, including
      hyperverbosity, sedative medications, polydipsia (psychogenic and secondary to a
      comorbidity of diabetes insipidus), and neuroleptic side effects. 

PMID- 23956912
TI  - Delayed presentation of traumatic diaphragmatic rupture with herniation of the
      left kidney and bowel loops.
AB  - Rupture of the diaphragm mostly occurs following major trauma. We report a case
      of delayed presentation of traumatic diaphragmatic hernia on the left side in a
      44-year-old male who presented two weeks after a minor blunt trauma. Left kidney
      and intestinals coils were found to herniate through the diaphragmatic tear. This
      case demonstrates the importance of considering the diagnosis in all cases of
      blunt trauma of the trunk. It also illustrates the rare possibility of herniation
      of kidney through the diaphragmatic tear. 

PMID- 23956913
TI  - Imaging characteristics of occipital bone osteoblastoma.
AB  - Osteoblastoma is a rare benign tumor of the calvarium. We present the case of a
      20-year-old female with occipital osteoblastoma and discussion of imaging
      modalities of calvarial osteoblastoma. To our knowledge, this is the ninth
      reported case of occipital osteoblastoma. Imaging characterization of
      osteoblastoma may vary. Plain radiograph, CT, MRI, and CT angiography establish
      osteoblastoma characterization and vascular supply prior to surgical resection. 

PMID- 23956914
TI  - Spontaneous Coronary Artery Dissection in a Male Patient with Takayasu's
      Arteritis and Antiphospholipid Antibody Syndrome.
AB  - We present a case of a 34-year-old male who presented to the emergency ward with
      fever and abdominal pain. The diagnosis of Takayasu's arteritis and also
      antiphospholipid syndrome was made during an imaging workup of deep-vein
      thrombosis. A spontaneous coronary artery dissection was revealed in coronary CT
      angiography requested for chest pain and dyspnea. The patient was treated
      medically and discharged on close followup. The concurrence of spontaneous
      coronary artery dissection with antiphospholipid syndrome and Takayasu's
      arteritis has not been reported in the previous literature. The possibility of a
      spontaneous coronary artery dissection should be considered in patients
      presenting with both diseases. 

PMID- 23956915
TI  - A patient with systemic lupus erythematosus complicated by neurological symptoms
      of toluene poisoning.
AB  - We report a patient with systemic lupus erythematosus complicated by toluene
      poisoning. She had erythema, alopecia, arthralgia, and various neurological
      symptoms. Laboratory findings showed leukocytopenia, low levels of complements,
      and anti-dsDNA antibody. However, normal interleukin-6 level and IgG index of
      cerebrospinal fluid and brain magnetic resonance imaging and single photon
      emission computed tomography findings suggested that her neurological symptoms
      were caused by metabolic disorder but not neuropsychiatric systemic lupus
      erythematosus. Erythema, alopecia, and arthralgia improved rapidly after
      administration of prednisolone and tacrolimus, whereas neurological symptoms
      improved only gradually. Because of a history of exposure to toluene, her
      neurological symptoms were considered to be due to toluene poisoning. The
      differentiation of toluene poisoning from neuropsychiatric systemic lupus
      erythematosus based on symptoms is difficult because both induce various
      neuropsychiatric disorders. Laboratory findings of cerebrospinal fluid,
      radiological findings, and medical interview were useful for differentiation of
      toluene poisoning from neuropsychiatric systemic lupus erythematosus. 

PMID- 23956916
TI  - Palpable purpura with an unexpected outcome.
AB  - Scurvy is a potentially lethal condition caused by inadequate vitamin C intake.
      Hypovitaminosis of vitamin C causes vessel fragility and follicular
      hyperkeratosis that can lead to palpable purpuric skin lesions. In this case
      report, we aim to remind readers that scurvy still occurs in Western countries
      and that the clinical presentation may resemble vasculitis. 

PMID- 23956917
TI  - A case of concomitant perforated acute cholecystitis and pancreatitis.
AB  - Introduction. Concomitant cholecystitis and gallstone pancreatitis is an
      infrequent clinical encounter, reported sparsely in the literature. Concurrent
      acute cholecystitis and pancreatitis complicated by gall bladder perforation has
      not been reported before. Presentation of Case. We report a 39-year-old female
      presenting with concomitant cholecystitis and acute pancreatitis, complicated by
      gallbladder perforation. Discussion. There is much controversy surrounding the
      timing of cholecystectomy following gallstone pancreatitis, with the recent
      literature suggesting that "early" operation is safe. In the current case,
      gallbladder perforation altered the "routine" management of gallstone
      pancreatitis and posed as a management dilemma. Conclusion. Clinical judgement
      dictated timing of operative management and ultimately cholecystectomy was
      performed safely. 

PMID- 23956918
TI  - Surgical resection of ruptured fibrolamellar hepatocellular carcinoma.
AB  - Fibrolamellar hepatocellular carcinoma (FLH) is a rare primary tumor of the
      liver, which typically arises from noncirrhotic livers and affects patients below
      the age of 35. We report on a 29-year-old male patient who presented with a
      ruptured FLH and was treated with surgical resection. Options for treatment and
      review of the management are described. 

PMID- 23956919
TI  - Ischemic Gangrene of the Glans following Penile Prosthesis Implantation.
AB  - The development of ischemic gangrene of the penis following implantation of
      prosthesis is unusual, and very few cases are available in the literature. As a
      result, no established treatment protocol is available. We report our experience
      within a case of gangrene of the glans following implantation of a three
      component prosthesis. We present a 53-year-old male, smoker with diabetes and
      hypercholesterolemia, who underwent surgery for the insertion of a penile
      prosthesis with 3 components to correct his erectile dysfunction and severe
      Peyronie's disease. The procedure was carried out without incidents. During the
      postoperative period, the patient began to complain from penile and perineal
      pain. He developed avascular necrosis of the glans. The necrosed area was
      excised. Four weeks later, he developed fever and perineal pain arriving to the
      emergency room with the prosthesis extruding through the glans. He had emergency
      surgery to remove the prosthesis plus surgical lavage and was prescribed broad
      spectrum antibiotic therapy. Four weeks later, the penis was completely
      revascularized and reepithelialized. Ischemic gangrene following penile
      prosthesis implantation takes place in patients with poor peripheral
      vascularisation. Diabetes mellitus has been the common denominator to all of the
      reported cases. 

PMID- 23956920
TI  - Simultaneous right retroperitoneal schwannoma and left renal hydatid cyst.
AB  - Retroperitoneal schwannomas are quite rare tumors. Isolated renal hydatid cyst is
      also rare, and it forms 2-4% of hydatid disease. Because of their infrequent
      occurrence, nonspecific signs and symptoms, and lack of distinguishing radiologic
      features, we report herein a case of right retroperitoneal mass in a 26-year-old
      woman which was found to be benign schwannoma following a percutaneous core
      needle biopsy and a large cortical cyst in the lower pole of the left kidney
      which was diagnosed as isolated renal hydatid cyst following exploration. 

PMID- 23956921
TI  - First case of complete bladder duplication in the coronal plane with concomitant
      duplication of the urethra in an adult male.
AB  - Duplication of the lower urinary tract is a very rare congenital anomaly which is
      diagnosed either at birth or during early childhood. These rare malformations are
      most of the times accompanied by other concomitant anomalies and are therefore
      diagnosed immediately after birth. In some even rarer cases there are no
      concomitant anomalies and symptoms thus leading to a diagnosis later in
      childhood. This is the first case in the literature of complete bladder
      duplication in the coronal plane with concomitant duplication of the urethra and
      no other associated anomalies in a 52-year-old male who remained asymptomatic and
      therefore undiagnosed for more than 5 decades. 

PMID- 23956922
TI  - Three-dimensional dual-energy computed tomography for enhancing stone/stent
      contrasting and stone visualization in urolithiasis.
AB  - The use of dual-energy computed tomography (DECT) for evaluating urinary calculi
      has been appreciated due to the modality's capability of differentiating between
      uric acid (UA) and non-UA stones, which are color coded based on a postprocessing
      algorithm. No other imaging modality or laboratory test is able to identify the
      stone composition without first attaining the stone material. Knowledge of the
      stone composition is clinically significant since UA calculi may be treated
      medically whereas non-UA calculi may require surgical removal. Regardless of the
      stone type, ureteral stents are often placed to prevent or treat obstruction.
      Recent work has demonstrated that commonly used stents are also colored based on
      their dual energy characteristics and may thereby either improve or obscure the
      identification of adjacent calculi. Herein, we report the case of a 65-year-old
      man who underwent percutaneous nephrolithotomy of a large staghorn stone with
      subsequent significant residual stone fragments noted on a follow-up scan. By
      using three-dimensional DECT and taking advantage of color contrasting, the stone
      composition, burden, shape, and boundary were clearly depicted apart from the
      adjacent stent, resulting in successful medical treatment and obviating the need
      for further surgical intervention. 

PMID- 23956923
TI  - Carcinosarcoma of the bladder: a case report and review of the literature.
AB  - Carcinosarcoma of the urinary bladder is a rare neoplasm that is composed of
      malignant epithelial and mesenchymal components. In these tumors, histogenesis
      and biological behaviour remain controversial. Approximately 70 cases have been
      reported in the literature, usually as case reports or a small series. A series
      of 221 cases using the Surveillance, Epidemiology and End Results (SEER) Program
      database has been reported recently. Optimal treatment is uncertain. Herein, we
      report a case of sarcomatoid carcinoma of urinary bladder of a farmer aged 84
      years old with a year history of hematuria and dysuria. A transurethral resection
      of the tumor (TUR-T) revealed a carcinosarcoma. The patient underwent radical
      cystectomy, and there is no tumor recurrence for 15 months after treatments. 

PMID- 23956924
TI  - Cerebral Hyperperfusion Syndrome following Protected Carotid Artery Stenting.
AB  - The cerebral hyperperfusion syndrome is a very rare complication after
      revascularization of the carotid artery and accompanied by postoperative or
      postinterventional hypertension in almost all patients. We report a case of a 77
      year-old man who developed a complete aphasia and increased right-sided weakness
      following endovascular treatment of severe occlusive disease of the left internal
      carotid artery. We discuss the risk and management of cerebral hyperperfusion
      syndrome after carotid artery stenting. 

PMID- 23956925
TI  - New approaches to thyroid hormones and purinergic signaling.
AB  - It is known that thyroid hormones influence a wide variety of events at the
      molecular, cellular, and functional levels. Thyroid hormones (TH) play pivotal
      roles in growth, cell proliferation, differentiation, apoptosis, development, and
      metabolic homeostasis via thyroid hormone receptors (TRs) by controlling the
      expression of TR target genes. Most of these effects result in pathological and
      physiological events and are already well described in the literature. Even so,
      many recent studies have been devoted to bringing new information on problems in
      controlling the synthesis and release of these hormones and to elucidating
      mechanisms of the action of these hormones unconventionally. The purinergic
      system was recently linked to thyroid diseases, including enzymes, receptors, and
      enzyme products related to neurotransmitter release, nociception, behavior, and
      other vascular systems. Thus, throughout this text we intend to relate the
      relationship between the TH in physiological and pathological situations with the
      purinergic signaling. 

PMID- 23956926
TI  - Infiltrative cutaneous hemangiolipoma in a goat.
AB  - An approximately 4-year-old castrated male, Saanen cross goat presented to the
      Colorado State University Veterinary Teaching Hospital for evaluation and removal
      of a 22 cm * 22 cm, dark red, thickened, and crusted cutaneous lesion along the
      left ventrolateral thorax. An initial incisional biopsy performed approximately 8
      weeks earlier was suspicious for cutaneous hemangiosarcoma. Surgical excision was
      deemed to be the most appropriate treatment option for this goat. A complete
      physical exam, complete blood count, and chemistry profile were performed and
      results were within normal limits. Thoracic radiographs and abdominal ultrasound
      were performed to rule out metastatic disease and comorbid conditions; no
      metastatic lesions or other abnormalities were observed. En bloc surgical
      excision of the affected skin was performed and the entire tissue was submitted
      for histopathology. A final diagnosis of cutaneous hemangiolipoma was reached
      upon extensive sectioning and histologic examination of the larger tissue
      specimen. The goat recovered well from surgery and has had no further
      complications up to 9 months postoperatively. To our knowledge, this is the first
      case report of a hemangiolipoma in a goat and surgical excision for such lesions
      appears to be a viable treatment method. 

PMID- 23956927
TI  - Quality control of natural product medicine and nutrient supplements.

PMID- 23956928
TI  - Combining electronic tongue array and chemometrics for discriminating the
      specific geographical origins of green tea.
AB  - The feasibility of electronic tongue and multivariate analysis was investigated
      for discriminating the specific geographical origins of a Chinese green tea with
      Protected Designation of Origin (PDO). 155 Longjing tea samples from three
      subareas were collected and analyzed by an electronic tongue array of 7 sensors.
      To remove the influence of abnormal measurements and samples, robust principal
      component analysis (ROBPCA) was used to detect outliers in each class. Partial
      least squares discriminant analysis (PLSDA) was then used to develop a
      classification model. The prediction sensitivity/specificity of PLSDA was
      1.000/1.000, 1.000/0.967, and 0.950/1.000 for longjing from Xihu, Qiantang, and
      Yuezhou, respectively. Electronic tongue and chemometrics can provide a rapid and
      reliable tool for discriminating the specific producing areas of Longjing. 

PMID- 23956929
TI  - Sphenoid Wing en plaque meningiomas: Surgical results and recurrence rates.
AB  - BACKGROUND: Sphenoid wing en plaque meningiomas are a subgroup of meningiomas
      defined by its particular sheet-like dural involvement and its disproportionately
      large bone hyperostosis. En plaque meningiomas represent 2-9% of all meningiomas
      and they are mainly located in the sphenoid wing. Total surgical resection is
      difficult and therefore these tumors have high recurrence rates. METHODS:
      Eighteen patients with sphenoid wing en plaque meningiomas surgically treated
      between January 1998 and December 2008 were included. Clinical, surgical, and
      follow-up data were retrospectively analyzed. RESULTS: Mean age was 52.2 years
      and 83% were female. Five patients presented extension of dural component into
      the orbit and six patients presented cavernous sinus infiltration. Adjuvant
      radiation therapy was performed in three patients. After a mean follow-up of 4.6
      years, five patients developed tumor recurrence - two patients were submitted to
      surgical treatment and the other three were submitted to radiation therapy. No
      patient presented recurrence after radiation therapy, whether performed
      immediately in the postoperative period or performed after recurrence. Patients
      without tumor extension to cavernous sinus or orbital cavity have the best
      prognosis treated with surgery alone. When tumor extension involves these
      locations the recurrence rate is high, especially in cases not submitted to
      adjuvant radiation therapy. CONCLUSION: Cavernous sinus and superior orbital
      fissure involvement are frequent and should be considered surgical limits.
      Postoperative radiation therapy is indicated in cases with residual tumor in
      these locations.

PMID- 23956930
TI  - Parasellar arachnoid cyst presenting with a nonpupil sparing third nerve palsy
      mimicking a posterior communicating artery aneurysm in an adult.
AB  - BACKGROUND: Arachnoid cysts are congenital lesions that contain fluid identical
      to cerebrospinal fluid (CSF). They usually do not communicate with CSF spaces.
      The vast majority of arachnoid cysts are congenital asymptomatic lesions that are
      discovered incidentally. Those lesions that do become symptomatic typically
      present in childhood with signs and symptoms of intracranial hypertension,
      seizures, and focal neurologic deficits specific to cyst location. CASE
      DESCRIPTION: A rare case of a parasellar arachnoid cyst presenting with
      oculomotor palsy is presented. The patient is a 45-year-old male who presented
      with acute onset diplopia and frontal headache. Neurologic examination revealed
      right ptosis, pupillary dilation, and opthalmoparesis consistent with an
      oculomotor palsy. Computed tomography (CT) scan and lumbar puncture failed to
      reveal evidence of a subarachnoid hemorrhage. Magnetic resonance imaging (MRI) of
      the brain demonstrated a 1 cm right parasellar nonenhancing mass that was
      hyperintense on T2 flair and with a fluid-fluid level concerning for a thrombosed
      posterior communicating artery (PCommA) aneurysm. There was an additional finding
      of a left occipital pole intraparenchymal hemorrhage in the setting of multiple
      hereditary cavernomas. Formal cerebral angiography revealed normal intracranial
      and extracranial vasculature. The patient was taken to the operating room for a
      right frontotemporal craniotomy, which revealed compression of the right
      oculomotor nerve by an arachnoid cyst. The cyst was fenestrated and resected with
      decompression of the oculomotor nerve. Postoperatively, the third nerve palsy had
      completely resolved. CONCLUSIONS: The above case demonstrates that arachnoid
      cysts should be considered in the differential for patients presenting with
      nonpupil sparing third nerve palsy and require timely surgical intervention. As
      is the case for an expanding PCommA aneurysm, prompt decompression results in the
      best chance for recovery of oculomotor nerve function.

PMID- 23956931
TI  - Feasibility of the custom-made titanium cranioplasty CRANIOTOP((r)).
AB  - BACKGROUND: With decompressive craniectomy for ischemic stroke, traumatic brain
      injury, and skull-infiltrating tumors, the need for cranioplasty has increased.
      Different materials for custom-made cranioplasties have been evaluated, but a
      gold standard could not yet be established. We report our experience with the new
      custom-made titanium CRANIOTOP((r))cranioplasty (CL Instruments, Germany).
      METHODS: A total of 50 consecutive patients received a CRANIOTOP cranioplasty
      within a 2 year interval. We reviewed the charts for time between initial surgery
      and cranioplasty, indication, complications, operative time, and cosmetic
      outcome. Postoperative imaging (computed tomography [CT] scan n = 48, magnetic
      resonance imaging (MRI) n = 5) was screened for fitting accuracy and for
      hemorrhages. RESULTS: The most common indication for craniectomy were diffuse
      edema due to traumatic brain injury (n = 17, 34%) and ischemic stroke (n = 12,
      24%). All patients were satisfied with the cosmetic result. In the postoperative
      CT scan accurate fitting was confirmed in all patients, the postoperative MRI was
      free of artifacts. Surgical revision was necessary in five patients because of
      empyema (n = 2), wound exposure (n = 2), and one cerebrospinal fluid fistula.
      Thus, the surgical morbidity was 10%. CONCLUSION: With due consideration of the
      limitations of this retrospective study, we feel the present data allow
      concluding that the custom-made titanium cranioplasty CRANIOTOP((r))is safe and
      feasible.

PMID- 23956932
TI  - Reflections on a career in neurosurgery.
AB  - Robert Heimburger recounts his career in neurosurgery, including some of the
      early years of modern neurosurgery and some of the contributions he made,
      particularly in the areas of early repair of myelomeningocele and spinal cord
      tethering, high-intensity focused ultrasound for the brain, stereotactic surgery,
      washing hair and scalps instead of shaving for cranial surgery, and neurosurgical
      consultation in Asian countries. Now aged 96, he continues to have a keen mind
      and thorough commitment to the profession that offered him a lifetime of
      inspiration and service. 

PMID- 23956933
TI  - Occipital-posterior cerebral artery bypass via the occipital interhemispheric
      approach.
AB  - BACKGROUND: The unavailability of the superficial temporal artery (STA) and the
      location of lesions pose a more technically demanding challenge when compared
      with conventional STA-superior cerebellar or posterior cerebral artery (PCA)
      bypass in vascular reconstruction procedures. To describe a case series of
      patients with cerebrovascular lesions who were treated using an occipital artery
      (OA) to PCA bypass via the occipital interhemispheric approach. METHODS: We
      retrospectively reviewed three consecutive cases of patients with cerebrovascular
      lesions who were treated using OA-PCA bypass. RESULTS: OA-PCA bypass was
      performed via the occipital interhemispheric approach. This procedure included:
      (1) OA-PCA bypass (n = 1), and combined OA-posterior inferior cerebellar artery
      and OA-PCA saphenous vein interposition graft bypass (n = 1) in patients with
      vertebrobasilar ischemia; (2) OA-PCA radial artery interposition graft bypass in
      one patient with residual PCA aneurysm. CONCLUSIONS: OA-PCA bypass represents a
      useful alternative to conventional STA-SCA or PCA bypass.

PMID- 23956934
TI  - Violence, mental illness, and the brain - A brief history of psychosurgery: Part
      3 - From deep brain stimulation to amygdalotomy for violent behavior, seizures,
      and pathological aggression in humans.
AB  - In the final installment to this three-part, essay-editorial on psychosurgery, we
      relate the history of deep brain stimulation (DBS) in humans and glimpse the
      phenomenal body of work conducted by Dr. Jose Delgado at Yale University from the
      1950s to the 1970s. The inception of the National Commission for the Protection
      of Human Subjects of Biomedical and Behavioral Research (1974-1978) is briefly
      discussed as it pertains to the "determination of the Secretary of Health,
      Education and Welfare regarding the recommendations and guidelines on
      psychosurgery." The controversial work - namely recording of brain activity, DBS,
      and amygdalotomy for intractable psychomotor seizures in patients with
      uncontrolled violence - conducted by Drs. Vernon H. Mark and Frank Ervin is
      recounted. This final chapter recapitulates advances in neuroscience and
      neuroradiology in the evaluation of violent individuals and ends with a brief
      discussion of the problem of uncontrolled rage and "pathologic aggression" in
      today's modern society - as violence persists, and in response, we move toward
      authoritarianism, with less freedom and even less dignity. 

PMID- 23956935
TI  - Gamma knife radiosurgery for typical trigeminal neuralgia: An institutional
      review of 108 patients.
AB  - BACKGROUND: In this study, we present the previously unreported pain relief
      outcomes of 108 patients treated at Gamma Knife of Spokane for typical trigeminal
      neuralgia (TN) between 2002 and 2011. METHODS: Pain relief outcomes were measured
      using the Barrow Neurological Institute (BNI) pain intensity scale. In addition,
      the effects gender, age at treatment, pain laterality, previous surgical
      treatment, repeat Gamma Knife radiosurgery (GKRS), and maximum radiosurgery dose
      have on patient pain relief outcomes were retrospectively analyzed. Statistical
      analysis was performed using Andersen 95% confidence intervals, approximate
      confidence intervals for log hazard ratios, and multivariate Cox proportional
      hazard models. RESULTS: All 108 patients included in this study were grouped into
      BNI class IV or V prior to GKRS. The median clinical follow-up time was
      determined to be 15 months. Following the first GKRS procedure, 71% of patients
      were grouped into BNI class I-IIIb (I = 31%; II = 3%; IIIa = 19%; IIIb = 18%) and
      the median duration of pain relief for those patients was determined to be 11.8
      months. New facial numbness was reported in 19% of patients and new facial
      paresthesias were reported in 7% of patients after the first GKRS procedure. A
      total of 19 repeat procedures were performed on the 108 patients included in this
      study. Following the second GKRS procedure, 73% of patients were grouped into BNI
      class I-IIIb (I = 44%; II = 6%; IIIa = 17%, IIIb = 6%) and the median duration of
      pain relief for those patients was determined to be 4.9 months. For repeat
      procedures, new facial numbness was reported in 22% of patients and new facial
      paresthesias were reported in 6% of patients. CONCLUSIONS: GKRS is a safe and
      effective management approach for patients diagnosed with typical TN. However,
      further studies and supporting research is needed on the effects previous
      surgical treatment, number of radiosurgery procedures, and maximum radiosurgery
      dose have on GKRS clinical outcomes.

PMID- 23956936
TI  - How effective is the local anesthetic infiltration of pin sites prior to
      application of head clamps: A prospective observational cohort study of
      hemodynamic response in patients undergoing elective craniotomy.
AB  - BACKGROUND: Use of Mayfield clamps is associated with potentially hazardous
      hemodynamic effects. Use of local anesthetic infiltration has yielded varying
      results in blunting of this response. The authors' objective was to study the
      effect of lidocaine with adrenaline infiltration at Mayfield pin sites on
      hemodynamic response in comparison with no intervention. METHODS: This was a
      prospective cohort study conducted at a tertiary care center from January 2012 to
      July 2012. Patents undergoing elective craniotomies over the study period were
      included and divided in two groups, Group A received lidocaine infiltration of
      the pin sites prior to insertion, while Group B did not. Hemodynamic response to
      pin application was then studied at various intervals. RESULTS: A total of 30
      patients were enrolled in each group. The baseline mean arterial pressure (MAP)
      and heart rate prior to pin placement in Groups A and B were comparable (P =
      0.985 and 0.313). The MAP at 60 seconds after application of skull pins was
      significantly different in the two groups; 86.13 (+/-9.73) mmHg versus 104.03 (+/
      12.95) mmHg (P < 0.001). However, the MAP at 30 minutes after application of
      skull pins in both groups was comparable (P = 0.585). The mean heart rate
      measured at 60 seconds after skull pin insertion in Group A was 78.23 (+/
      7.19)/min while in Group B, it was 103.07 (+/-6.98)/min, the difference being
      statistically significant (P < 0.001). CONCLUSION: Hemodynamic changes due to the
      application of Mayfield clamps during elective craniotomies can be effectively
      prevented by prior lidocaine with adrenaline infiltration of the pin insertion
      sites.

PMID- 23956937
TI  - It is our moral obligation and the time is now.

PMID- 23956938
TI  - Facial necrosis after endovascular Onyx-18 embolization for epistaxis.
AB  - BACKGROUND: Evolution in techniques and equipment has expanded the role,
      effectiveness, and safety of endovascular transarterial embolization for the
      treatment of severe epistaxis. Risks from this treatment approach include major
      ischemic complications. To date, there have been only a few reports of soft
      tissue necrosis following endovascular embolization for severe epistaxis; none
      involve the use of Onyx-18. CASE DESCRIPTION: We report the case of a 52-year-old
      woman who presented with epistaxis that was refractory to medical and surgical
      management, which lead to endovascular intervention and embolization with Onyx
      18. The patient subsequently developed nasal ala and facial necrosis as a result
      of the procedure. CONCLUSION: We report the use of Onyx-18 for the endovascular
      embolization of a patient with severe epistaxis and subsequent complications. In
      cases of severe epistaxis that warrant intervention in the form of embolization,
      ischemic complications are rare; however, ischemic complications may be
      unavoidable and should factor into the discussion regarding procedural risks.

PMID- 23956939
TI  - Dural metastasis of Ewing's sarcoma.
AB  - BACKGROUND: Metastatic Ewing's sarcoma to the central nervous system is an
      uncommon condition and debate concerning the true origin of its metastases is
      still up to date. To the best of our knowledge, only two cases of dural
      metastatic Ewing's sarcoma have been published in the English medical literature.
      We present an additional case in a 24-year-old female and discuss the
      pathogenesis of these unusual tumors with review of the relevant literature
      concerning their treatment and outcome. CASE DESCRIPTION: A 24-year-old female
      with previous history of pelvis Ewing's sarcoma and recently discovered lung
      metastases, presented with moderate headache for the past 2 weeks and weakness in
      her left leg for the past 2 days. Computed tomography scan and magnetic resonance
      imaging revealed an extra-axial right frontoparietal mass invading the superior
      sagittal sinus but with clear delineation with brain parenchyma. Imaging features
      were suggestive of a meningioma as no abnormalities in the skull abutting to the
      tumor were noted. The patient underwent surgical removal of her tumor. Near total
      resection was achieved and histological examination showed evidence of metastatic
      Ewing's sarcoma. Postoperative adjuvant radiation and chemotherapy were
      administered. The patient improved well postoperatively with full recovery of her
      motor weakness. She is symptom free with no signs of progression, at most recent
      follow-up, 8 months after surgery. CONCLUSION: Despite its rarity, metastatic
      Ewing's sarcoma must be considered in the differential diagnosis of extra-axial
      dural masses particularly meningiomas.

PMID- 23956940
TI  - Novel devices for intraoperative monitoring of glossopharyngeal and vagus nerves
      during skull base surgery.
AB  - BACKGROUND: Swallowing disturbance is among the most burdensome complications
      suffered by patients with glossopharyngeal and vagus nerve involvement in lesions
      adjacent the jugular foramen. For monitoring these nerves, we have developed new
      devices that comprised four contacts adhering to the surface of the cuff of an
      endotracheal tube, with attachment the posterior pharyngeal wall. To determine
      whether these devices are useful for monitoring the glossopharyngeal and vagus
      nerves and predicting postoperative swallowing dysfunction in patients undergoing
      removal of skull base tumors involving these nerves. METHODS: We studied 10
      patients. Compound muscle action potentials (CMAPs) were recorded from the
      posterior pharyngeal wall by stimulating the glossopharyngeal or vagus nerve in
      order to identify the nerve course, especially in patients showing severe nerve
      distortion due to the tumor. Pharyngeal motor evoked potential (PhMEP) elicited
      by transcranial electrical stimulation were recorded in all patients. The
      correlation between the final to baseline PhMEP ratio and postoperative
      swallowing function was examined. RESULTS: Responses were obtained in six of the
      seven patients in whom CMAP monitoring was performed. Deterioration of swallowing
      function postoperatively was demonstrated in six of seven (86%) patients with
      intraoperative PhMEP ratios <50%. None of the three patients with intraoperative
      PhMEP ratios >50% showed deterioration of swallowing function after surgery,
      although the one patient already had severe swallowing dysfunction requiring
      preoperative tracheostomy. CONCLUSIONS: Our novel devices were useful for
      monitoring the glossopharyngeal and vagus nerves in patients undergoing removal
      of skull base tumors involving these nerves.

PMID- 23956941
TI  - Techniques for placement of grid and strip electrodes for intracranial epilepsy
      surgery monitoring: Pearls and pitfalls.
AB  - BACKGROUND: Placement of intracranial strip and grid electrodes for recording
      cortical electrocorticography is important as part of the workup of patients who
      are being considered for resective epilepsy surgery. In recent decades, the
      indications and techniques for intracranial epilepsy monitoring have been
      refined. METHODS: In this article, the authors describe the techniques for
      intraoperative placement of grid and strip electrodes for extraoperative study of
      a seizure focus. RESULTS: Methods to enhance the efficacy of this technique while
      minimizing complications are reviewed. CONCLUSIONS: Intracranial epilepsy
      monitoring with grid and strip electrodes is a useful tool for the planning of
      resective epilepsy surgery. Techniques to advance the safety and minimize
      complications will lead to improved outcomes.

PMID- 23956942
TI  - A case of large B-cell intravascular lymphoma in the brain.
AB  - BACKGROUND: Intravascular lymphoma is a rare and fatal disease that can have
      central nervous system (CNS) manifestations. It is usually a diagnosis made
      postmortem. This is partly due to its varied presentation, which lends itself to
      the complexity of diagnosis. CASE DESCRIPTION: We report a rare case of
      intravascular lymphoma in the brain found antemortem. CONCLUSION: Review of the
      literature shows that a timely diagnostic tissue biopsy together with aggressive
      combination chemotherapy treatment can improve patient outcome.

PMID- 23956943
TI  - Comparison of total versus partial revision of primary ventriculoperitoneal shunt
      failures.
AB  - BACKGROUND: Optimal surgical management of patients presenting with primary shunt
      failure in the era of neuroendoscopy remains complex. The value of replacing the
      entire shunt system as opposed to a single shunt component has not been assessed
      extensively. METHODS: In a retrospective study, the records of all patients who
      underwent their first shunt revision due to mechanical obstruction between
      September 2007 and December 2011 were reviewed. Shunt revisions were classified
      as total (entire shunt replaced) or partial (only malfunctioning component
      replaced). Patients having a minimum follow-up of 1 year after primary shunt
      revision were included in the study. Kaplan-Meier (shunt survival curves) and log
      rank analysis were used to compare failure rates between partially and totally
      revised shunts. RESULTS: Records of 62 patients in whom cause of primary shunt
      failure was obstruction (P roximal or distal) were analyzed retrospectively. At
      the end of follow-up period, 26 out of 28 partial revision group and 22 out of 34
      total revision group had shunt failure. The median survival of the shunt in the
      partial revision and total revision groups was 60 and 270 days, respectively. The
      method (partial/total revision) related difference in shunt survival duration was
      statistically significant as shown by log-rank analysis (log-rank test value =
      5.94 and P < 0.05). CONCLUSION: Partial revision of shunt predisposes to
      accelerated shunt failure as compared with total revision in cases of obstructed
      ventriculoperitoneal shunt.

PMID- 23956944
TI  - Screening for Neurocognitive Impairment in HIV Individuals: The Utility of the
      Montreal Cognitive Assessment Test.

PMID- 23956945
TI  - In-Cell NMR Spectroscopy-In vivo Monitoring of the Structure, Dynamics, Folding,
      and Interactions of Proteins at Atomic Resolution.

PMID- 23956946
TI  - Immunoproteasome Activation During Early Antiviral Response in Mouse Pancreatic
      beta-cells: New Insights into Auto-antigen Generation in Type I Diabetes?
AB  - Type 1 diabetes results from autoimmune destruction of the insulin producing
      pancreatic beta-cells. The immunoproteasome, a version of the proteasome that
      collaborates with the 11S/PA28 activator to generate immunogenic peptides for
      presentation by MHC class I molecules, has long been implicated in the onset of
      the disease, but little is known about immunoproteasome function and regulation
      in pancreatic beta-cells. Interesting insight into these issues comes from a
      recent analysis of the immunoproteasome expressed in pancreatic beta-cells during
      early antiviral defenses mediated by interferon beta (IFNbeta), a type I IFN
      implicated in the induction of the diabetic state in human and animal models.
      Using mouse islets and the MIN6 insulinoma cell line, Freudenburg et al. found
      that IFNbeta stimulates expression of the immunoproteasome and the 11S/PA28
      activator in a manner fundamentally similar to the classic immuno-inducer
      IFNgamma, with similar timing of mRNA accumulation and decline; similar
      transcriptional activation mediated primarily by the IRF1 and similar mRNA and
      protein levels. Furthermore, neither IFNbeta nor IFNgamma altered the expression
      of regular proteolytic subunits or prevented their incorporation into proteolytic
      cores. As a result, immunoproteasomes had stochastic combinations of immune and
      regular proteolytic sites, an arrangement that would likely increase the
      probability with which unique immunogenic peptides are produced. However,
      immunoproteasomes were activated by the 11S/PA28 only under conditions of ATP
      depletion. A mechanism that prevents the activation of immunoproteasome at high
      ATP levels has not been reported before and could have a major regulatory
      significance, as it could suppress the generation of immunogenic peptides as cell
      accumulate immunoproteasome and 11S/PA28, and activate antigen processing only
      when ATP levels drop. We discuss implications of these new findings on the link
      between early antiviral response and the onset of type 1 diabetes.

PMID- 23956947
TI  - Improved targeting and enhanced retention of the human, autologous, fibroblast
      derived, induced, pluripotent stem cells to the sarcomeres of the infarcted
      myocardium with the aid of the bioengineered, heterospecific, tetravalent
      antibodies.
AB  - Clinical trials, to regenerate the human heart injured by myocardial infarction,
      involve the delivery of stem cells to the site of the injury. However, only a
      small fraction of the introduced stem cells are detected at the site of the
      injury, merely two weeks after this therapeutic intervention. This significantly
      hampers the effectiveness of the stem cell therapy. To resolve the aforementioned
      problem, we genetically and molecularly bioengineered heterospecific, tetravalent
      antibodies (htAbs), which have both exquisite specificity and high affinity
      towards human, pluripotent, stem cells through the htAbs' domains binding SSEA-4,
      SSEA-3, TRA-1-60, and TRA-1-81, as well as towards the injured cardiac muscle
      through the htAbs' domains binding human cardiac myosin, alpha-actinin, actin,
      and titin. The cardiac tissue was acquired from the patients, who were receiving
      heart transplants. The autologous, human, induced, pluripotent stem cells
      (hiPSCs) were generated from the patients' fibroblasts by non-viral delivery and
      transient expression of the DNA constructs for: Oct4, Nanog, Sox2, Lin28, Klf4, c
      Myc. In the trials involving the htAbs, the human, induced, pluripotent stem
      cells anchored to the myocardial sarcomeres with the efficiency, statistically,
      significantly higher, than in the trials with non-specific or without antibodies
      (p < 0.0003). Moreover, application of the htAbs resulted in cross-linking of the
      sarcomeric proteins to create the stable scaffolds for anchoring of the stem
      cells. Thereafter, these human, induced pluripotent stem cells differentiated
      into cardiomyocytes at their anchorage sites. By bioengineering of these novel
      heterospecific, tetravalent antibodies and using them to guide and to anchor the
      stem cells specifically to the stabilized sarcomeric scaffolds, we demonstrated
      the proof of concept in vitro for improving effectiveness of regenerative therapy
      of myocardial infarction and created the foundations for the trials in vivo.

PMID- 23956948
TI  - Transpositional transgenesis with piggyBac.
AB  - Transposons are mobile genetic elements that are capable of self-directed
      excision and subsequent reintegration within the host genome. Transposase such as
      piggyBac, Sleeping Beauty and Tol2 catalyze these reactions and have shown
      potential as tools for the stable integration of transgenes when used in the
      binary plasmid mode. Recent modifications to the transposase and/or the terminal
      repeats of the transposon have increased their integration efficiency and/or
      specificity. We recently described the development of a piggyBac transposase
      system, the helper independent, single construct self-inactivating plasmid called
      GENIE. Here we describe the structure, safety and function of these
      transpositional vectors and their use in animal transgenesis and cell
      transfection.

PMID- 23956949
TI  - First report on class 1 integrons and Trimethoprim-resistance genes from dfrA
      group in uropathogenic E. coli (UPEC) from the Aleppo area in Syria.
AB  - Horizontal gene transfer (HGT) introduces advantageous genetic elements into
      pathogenic bacteria using tools such as class1 integrons. This study aimed at
      investigating the distribution of these integrons among uropathogenic E. coli
      (UPEC) isolated from patients in Aleppo, Syria. It also set to uncover the
      frequencies of the clinically relevant DfrA1 and DfrA17,7, as well as various
      associations leading to reduced susceptibility. This study involved 75
      Trimethoprim-resistant E. coli isolates from in- and outpatients with urinary
      tract infections (UTIs) from 3 major hospitals in Aleppo. Bacterial
      identification, resistance and extended-spectrum-beta-lactamase (ESBL) production
      testing were performed according to Clinical Laboratory Standards Institute
      guidelines. Detection of integrons and DfrA genes was done using PCR and
      statistical significance was inferred through chi2 (Fisher's) test. Class1
      integrons were detected in 54.6% of isolates while DfrA1 and DfrA17,7 were found
      in 16% and 70.6% of tested samples respectively. Furthermore, only DfrA17,7 were
      strongly associated with class1 integrons, as were reduced susceptibility to the
      majority of individual antibiotics, multidrug resistance and ESBL production.
      This study demonstrated the high prevalence of class1 integrons among UPEC
      strains in Aleppo, Syria, as well as their significant associations with MDR.
      This data give information for local healthcare provision using antibiotic
      chemotherapy.

PMID- 23956950
TI  - Pitfalls encountered while investigating genetic elements by PCR.
AB  - The unprecedented wealth of databases that have become available in the era of
      next-generation sequencing has considerably increased our knowledge of bacterial
      genetic elements (GEs). At the same time, the advent of single-cell based
      approaches has brought realization that unsuspected heterogeneity may occur in
      the bacterial population from a single colony. The increasing use of PCR-based
      techniques to study new GEs requires careful consideration of the possible
      different PCR targets associated with different subpopulations if incorrect or
      incomplete interpretations are to be avoided. In this commentary, confining
      ourselves to our direct experience, we illustrate some examples of PCR pitfalls
      that may be encountered while investigating GEs.

PMID- 23956951
TI  - Insertion sequence AS5 (IS AS5 ) is involved in the genomic plasticity of
      Aeromonas salmonicida.
AB  - The genome of the fish pathogen Aeromonas salmonicida subsp salmonicida harbors a
      large number of insertion sequences (ISs), many of which are located on plasmids.
      In the present study, we analyzed the small plasmid profile of A. salmonicida
      strains to identify evidences of plasmid alterations. Ten out of 78 strains
      analyzed displayed an unconventional plasmid profile. However the HER1104 strain
      was unique, having a positive PCR signal for pAsal1 plasmid despite not carrying
      this plasmid. Instead, HER1104 was bearing a plasmid at higher molecular weight
      than pAsal1. We characterized this new larger plasmid, which we called pAsal1B
      since it is a derivative of pAsal1 containing one more complete IS (ISAS5) than
      the parental plasmid. An additional 96 bp relic of ISAS5 was also present in
      pAsal1B. These results propose that ISAS5 is another active mobile genetic
      element in A. salmonicida subsp salmonicida and provided further proof of the
      genomic plasticity of this bacterium.

PMID- 23956952
TI  - Phenotypic Categorization and Profiles of Small and Large Hepatocellular
      Carcinomas.
AB  - We used a database of 4139 Taiwanese HCC patients to take a new approach (Network
      Phenotyping Strategy) to HCC subset identification. Individual parameters for
      liver function tests, complete blood count, portal vein thrombosis, AFP levels
      and clinical demographics of age, gender, hepatitis or alcohol consumption, were
      considered within the whole context of complete relationships, being networked
      with all other parameter levels in the entire cohort. We identified 4 multi
      parameter patterns for one tumor phenotype of patients and a separate 5 multi
      parameter patterns to characterize another tumor phenotype of patterns. The 2
      subgroups were quite different in their clinical profiles. The means of the tumor
      mass distributions in these phenotype subgroups were significantly different, one
      being associated with larger (L) and the other with smaller (S) tumor masses.
      These significant differences were seen systematically throughout the tumor mass
      distributions. Essential and common clinical components of L-phenotype patterns
      included simultaneously high blood levels of AFP and platelets plus presence of
      portal vein thrombosis. S included higher levels of liver inflammatory
      parameters. The 2 different parameter patterns of L and S subgroups suggest
      different mechanisms; L, possibly involving tumor-driven processes and S more
      associated with liver inflammatory processes.

PMID- 23956953
TI  - SCNH2 is a novel apelinergic family member acting as a potent mitogenic and
      chemotactic factor for both endothelial and epithelial cells.
AB  - The gut hormone apelin is a major therapeutic focus for several diseases
      involving inflammation and aberrant cell growth. We investigated whether apelin
      36 contained alternative bioactive peptides associated with normal physiology or
      disease. Amino acid sequence analysis of apelin-36 identified an amidation motif
      consistent with the formation of a secondary bioactive peptide (SCNH2). SCNH2 is
      proven to be mitogenic and chemotactic in normal/malignant cells and augments
      angiogenesis via a PTX-resistant/CT-X-sensitive G protein-coupled receptor
      (GPCR). Notably, SCNH2 is substantially more potent and sensitive than apelin-13
      and vascular endothelial growth factor-A. Endogenous SCNH2 is highly expressed in
      human tumors and placenta and in mouse embryonic tissues. Our findings
      demonstrate that SCNH2 is a new apelinergic member with critical pluripotent
      roles in angiogenesis related diseases and embryogenesis via a non-APJ GPCR.

PMID- 23956954
TI  - Social Networks among Residents in Recovery Homes.
AB  - Although evidence exists that substance abuse abstinence is enhanced when
      individuals in recovery are embedded in social networks that are cohesive, few
      studies examined the network structures underlying recovery home support systems.
      In two studies, we investigated the mechanisms through which social environments
      affect health outcomes among two samples of adult residents of recovery homes.
      Findings from Study 1 (n = 150) indicated that network size and the presence of
      relationships with other Oxford House (OH) residents both predicted future
      abstinence. Study 2 (n = 490) included individuals who lived in an OH residence
      for up to 6 months, and their personal relationship with other house residents
      predicted future abstinence. Implications of these findings are discussed.

PMID- 23956955
TI  - Interactions Between Hepatitis C Virus and Mitochondria: Impact on Pathogenesis
      and Innate Immunity.
AB  - Hepatitis C virus (HCV) causes a persistent chronic infection of hepatocytes
      resulting in progressive fibrosis and carcinogenesis. Abnormalities in
      mitochondria are prominent features of clinical disease where ultrastructural
      changes, alterations in electron transport, and excess reactive oxygen species
      (ROS) production occur. These mitochondrial abnormalities correlate with disease
      severity and resolve with viral eradication. Multiple viral proteins,
      particularly core and NS3/4a bind to mitochondria. The core and NS5a proteins
      primarily cause ER stress, ER Ca2+ release and enhance direct transfer of Ca2+
      from ER to mitochondria. This results in electron transport changes, increased
      ROS production and sensitivity to mitochondrial permeability transition and cell
      death. The viral protease, NS3/4a, binds to mitochondria as well where it cleaves
      an important signaling adapter, MAVS, thus preventing viral clearance by
      endogenous interferon production. This review discusses the mechanisms by which
      HCV causes mitochondrial changes and consequences of these for disease.

PMID- 23956956
TI  - Genetic and Environmental Influences on Rumination, Distraction, and Depressed
      Mood in Adolescence.
AB  - Rumination is an established cognitive vulnerability for depression. Despite
      substantial work on the environmental origins of rumination, the heritability of
      rumination has not been examined and it is not known whether rumination accounts
      for some of the genetic vulnerability associated with depression. 756 adolescent
      twins ages 12-14 years completed the Response Styles Questionnaire and multiple
      measures of depressive symptoms. Brooding correlated positively and distraction
      correlated negatively with concurrent depressive symptoms. Estimated
      heritabilites were 54% for depression, 21% for brooding, 37% for reflection, and
      30% for distraction. Bivariate genetic analyses suggested that (1) individual
      differences in distraction share both genetic and environmental sources of
      variation with depression; and (2) although the heritable influences on brooding
      are small, these heritable influences account for the majority of the
      relationship between brooding and depression (h2 = .62).

PMID- 23956957
TI  - In vivo 1H magnetic resonance spectroscopy in young-adult daily marijuana users.
AB  - To date, there has been little work describing the neurochemical profile of
      young, heavy marijuana users. In this study, we examined 27 young-adult marijuana
      users and 26 healthy controls using single-voxel magnetic resonance spectroscopy
      on a 3 T scanner. The voxel was placed in the dorsal striatum, and estimated
      concentrations of glutamate + glutamine, myo-inositol, taurine + glucose, total
      choline and total N-acetylaspartate were examined between groups. Therewere no
      overall group effects, but two metabolites showed group by sex interactions.
      Lower levels of glutamate + glutamine (scaled to total creatine) were observed in
      female, but not male, marijuana users compared to controls. Higher levels of myo
      inositol were observed in female users compared to female non-users and to males
      in both groups. Findings are discussed in relation to patterns of corticostriatal
      connectivity and function, in the context of marijuana abuse.

PMID- 23956958
TI  - Frailty and healthcare utilization among patients with heart failure in the
      community.
AB  - OBJECTIVES: The aim of this study was to determine the prevalence of frailty in a
      community cohort of patients with heart failure (HF) and to determine whether
      frailty is associated with healthcare utilization. BACKGROUND: Frailty is
      associated with death in patients with HF, but its prevalence and impact on
      healthcare utilization in patients with HF are poorly characterized. METHODS:
      Residents of Olmsted, Dodge, and Fillmore counties in Minnesota with HF between
      October 2007 and March 2011 were prospectively recruited to undergo frailty
      assessment. Frailty was defined as 3 or more of the following: unintentional
      weight loss, exhaustion, weak grip strength, and slowness and low physical
      activity measured by the SF-12 physical component score. Intermediate frailty was
      defined as 1 or 2 components. Negative binomial regression was used to examine
      the association between outpatient visits and frailty; Andersen-Gill models were
      used to determine if frailty predicted emergency department (ED) visits or
      hospitalizations. RESULTS: Among 448 patients (mean age 73 +/- 13 years, 57%
      men), 74% had some degree of frailty (19% frail, 55% intermediate frail). Over a
      mean follow-up period of 2.0 +/- 1.1 years, 20,164 outpatient visits, 1,440 ED
      visits, and 1,057 hospitalizations occurred. After adjustment for potential
      confounders, frailty was associated with a 92% increased risk for ED visits and a
      65% increased risk for hospitalizations. The population-attributable risk
      associated with any degree of frailty was 35% for ED visits and 19% for
      hospitalizations. CONCLUSIONS: Frailty is common among community patients with HF
      and is a strong and independent predictor of ED visits and hospitalizations.
      Because frailty is potentially modifiable, it should be incorporated in the
      clinical evaluation of patients with HF.

PMID- 23956959
TI  - Induction of the Proepicardium.
AB  - The proepicardium is a transient extracardiac embryonic tissue that gives rise to
      the epicardium and a number of coronary vascular cell lineages. This important
      extracardiac tissue develops through multiple steps of inductive events, from
      specification of multiple cell lineages to morphogenesis. This article will
      review our current understanding of inductive events involved in patterning of
      the proepicardium precursor field, specification of cell types within the
      proepicardium, and their extension and attachment to the heart.

PMID- 23956960
TI  - The effects of environmental pollution and climate change on allergic diseases.

PMID- 23956962
TI  - The pH of water from various sources: an overview for recommendation for patients
      with atopic dermatitis.
AB  - BACKGROUND: Patients with atopic dermatitis (AD) have increased susceptibility to
      irritants. Some patients have questions about types of water for bathing or skin
      cleansing. OBJECTIVE: We studied the pH of water from various sources to give an
      overview for physicians to recommend patients with AD. METHODS: Water from
      various sources was collected for measurement of the pH using a pH meter and pH
      indicator strips. RESULTS: Bottled drinking still water had pH between 6.9 and
      7.5 while the sparkling type had pH between 4.9 and 5.5. Water derived from home
      water filters had an approximate pH of 7.5 as same as tap water. Swimming pool
      water had had pH between 7.2 and 7.5 while seawater had a pH of 8. Normal saline
      and distilled water had pH of 5.4 and 5.7, respectively. Facial mineral water had
      pH between 7.5 and 8, while facial makeup removing water had an acidic pH.
      CONCLUSION: Normal saline, distilled water, bottled sparkling water and facial
      makeup removing water had similar pH to that of normal skin of normal people.
      However, other factors including benefits of mineral substances in the water in
      terms of bacteriostatic and anti-inflammation should be considered in the
      selection of cleansing water.

PMID- 23956961
TI  - Allergic diseases and air pollution.
AB  - The prevalence of allergic diseases has been increasing rapidly, especially in
      developing countries. Various adverse health outcomes such as allergic disease
      can be attributed to rapidly increasing air pollution levels. Rapid urbanization
      and increased energy consumption worldwide have exposed the human body to not
      only increased quantities of ambient air pollution, but also a greater variety of
      pollutants. Many studies clearly demonstrate that air pollutants potently trigger
      asthma exacerbation. Evidence that transportation-related pollutants contribute
      to the development of allergies is also emerging. Moreover, exposure to
      particulate matter, ozone, and nitrogen dioxide contributes to the increased
      susceptibility to respiratory infections. This article focuses on the current
      understanding of the detrimental effects of air pollutants on allergic disease
      including exacerbation to the development of asthma, allergic rhinitis, and
      eczema as well as epigenetic regulation. 

PMID- 23956963
TI  - Time trends, ethnicity and risk factors for eczema in New Zealand children: ISAAC
      Phase Three.
AB  - BACKGROUND: Eczema is a common chronic disease which has significant morbidity
      and costs for children and their families. Phase One (1993) of the International
      Study of Asthma and Allergies in Childhood (ISAAC) found a high prevalence of
      symptoms of eczema in New Zealand. OBJECTIVE: In Phase Three (2001-3) we aimed to
      answer these three questions: Is the prevalence of eczema changing over time?;
      Are there ethnic differences in prevalence?; and What are the risk factors for
      eczema? METHODS: Five New Zealand centres participated in ISAAC Phases One and
      Three using the same methodology. Questionnaires about ethnicity, symptoms of
      eczema and environmental factors were completed by parents of 6-7 year olds
      (children) and self-completed by 13-14 year olds (adolescents). Prevalence and
      change per year were calculated by centre, ethnicity and gender. Prevalence
      differences between centres and associations with environmental factors were
      examined using logistic regression. RESULTS: There was little change in
      prevalence over time for the children, and a decrease in prevalence for the
      adolescents. Prevalence was higher among Maori and even higher among Pacific
      participants than among European children. Positive associations with current
      eczema symptoms were found for both age groups for truck traffic in the street of
      residence, and current paracetamol consumption, and for children only,
      antibiotics or paracetamol in the 1st year of life. Inverse associations were
      found with residence in New Zealand less than 5 years, consumption of milk,
      seafood, and eggs, and presence of a dog in the home. CONCLUSION: Eczema remains
      a significant problem, particularly for young Maori and Pacific New Zealanders in
      whom less recognition of eczema and poorer access to effective, sustained eczema
      management may be contributing factors. Reverse causation may explain all the
      environmental findings apart from truck traffic which is increasing in New
      Zealand.

PMID- 23956964
TI  - Sensitization patterns of cow's milk and major components in young children with
      atopic dermatitis.
AB  - BACKGROUND: Cow's milk (CM) is one of the most common food allergens in children
      with atopic dermatitis (AD), and the component-specific immunoglobulin E
      (component-IgE) measurement has recently become available. OBJECTIVE: This study
      aimed to investigate the sensitization patterns to CM and 3 major components and
      their clinical values in young Korean children with AD. METHODS: Cow's milk
      specific IgE (CM-IgE), alpha-lactalbumin-specific IgE (ALA-IgE), beta
      lactoglobulin-specific IgE (BLG-IgE), and casein-specific IgE (Cas-IgE) levels
      from the sera of patients with AD were measured using the UniCAPTM system (Thermo
      Fisher Scientific, Sweden) and collected from January 2004 to December 2010.
      Patients >= 4 years of age were excluded from the analysis. RESULTS: A total of
      950 patients diagnosed with AD were ultimately enrolled in the study. Among them,
      471 (49.6%) patients were sensitized to CM (CM-IgE[+], > 0.35 kU/L).
      Sensitization to casein (n = 349, 74.1%) was most common, followed by ALA (n =
      283, 60.1%), and BLG (n = 245, 52.5%). Meanwhile, 95 patients had at least 2
      follow-up tests. Eighty (84.2%) of these patients tested positive to CM, and the
      casein sensitization rate was the highest (n = 65, 81.3%). In addition, 479
      (50.4%) patients were not sensitized to CM (CM-IgE[-], <= 0.35 kU/L) but 35
      (7.3%) patients were sensitized to at least one component. Among them, a
      telephone survey was accessible in 21 cases. A total of 8 (38.1%) patients still
      suffered from adverse reactions after consuming milk and/or dairy foods.
      CONCLUSION: Casein was the most commonly and persistently sensitized component in
      CM-IgE(+) children with AD. Measuring CM component IgE antibodies, especially Cas
      IgE, is helpful for evaluating problematic allergens in young children with AD.

PMID- 23956965
TI  - T cell transcriptional factors in allergic rhinitis and its association with
      clinical features.
AB  - BACKGROUND: Th2 cells are crucially important in allergic disease and the
      possible involvement of Treg and Th17 cells has not been clearly identified.
      OBJECTIVE: To identify the mRNA expression of T cell transcription factors in
      nasal mucosa in patients with allergic rhinitis (AR) and to reveal their
      correlations with clinical features. METHODS: Eighteen patients with AR and 12
      controls with turbinate hypertrophy were included. mRNA expression of the
      following transcriptional factors in nasal mucosa were measured by quantitative
      polymerase chain reaction; T-bet (Th1), GATA3 (Th2), retinoic acid-related orphan
      receptor C (RORC; Th17), and forkhead box P3 (Foxp3; Treg). mRNA expression was
      compared among groups and correlation between mRNA expression level and clinical
      features (rhinitis symptoms, eosinophil count, and IgE) were also investigated.
      RESULTS: GATA3 and RORC were significantly increased and Foxp3 was significantly
      decreased in the AR group. Moderate-to-severe AR group also had increased
      expression of GATA3 and RORC than mild AR group, suggesting severity of AR
      influence expression of transcription factors. Correlation analysis showed that
      none of these transcription factors were associated with severity of clinical
      symptoms, eosinophil counts and skin prick test severity and that IgE level was
      significantly correlated with expression level of GATA3 and RORC, suggesting an
      association of IgE production with Th2 and Th17 cells. CONCLUSION: Increased mRNA
      expression of GATA3 (Th2), increased expression of RORC and decreased expression
      of Foxp3 may be important in pathogenesis of AR. GATA3 and RORC may be closed
      related with IgE level.

PMID- 23956966
TI  - IL-13 and STAT6 signaling involve in low dose lipopolysaccharide induced murine
      model of asthma.
AB  - BACKGROUND: We reported that level of lipopolysaccharide (LPS) exposure
      determined the type of airway inflammation in a murine model of asthma.
      OBJECTIVE: The purpose of this study is to evaluated the role of IL-13 in low
      dose LPS induced murine model of asthma using IL-13 and signal transducer and
      activator of transcription 6 (STAT6) deficient mice. METHODS: Mice were
      sensitized with an intranasal application of LPS-depleted ovalbumin (OA) and
      different doses of LPS (0.1 and 10 ug), and then challenged intranasally with OA
      alone. The phenotype changes between wild type (WT) and IL-13(-/-) mice and
      between WT and STAT6(-/-) mice were evaluated. RESULTS: We confirmed again that
      low and high dose LPS resulted in different phenotypes of murine asthma. In the
      present study, we observed that phenotypes of murine asthma induced by low dose
      LPS were abolished in the homozygous null mutation of the IL-13 and STAT6 gene.
      However, those changes were not shown in mice sensitized OA plus high dose LPS.
      CONCLUSION: IL-13 plays an important role in low dose LPS induced murine model of
      asthma. Our results provided a new insight in understanding of the potential role
      of IL-13 in innate immunity in human allergic asthma.

PMID- 23956967
TI  - The global decline in asthma death rates: can we relax now?
AB  - Whilst global asthma mortality seems to be decreasing, childhood asthma incidence
      is rising, and early warnings from Australia show an increase in asthma-related
      deaths in under-15s; this article considers whether we should view the future
      impact of asthma with trepidation. Age-adjusted mortality statistics for asthma
      have been reevaluated to provide an international standard. Comparisons across
      regions and time are complex, yet over the last two decades asthma mortality has
      clearly decreased, coinciding with a significant change in asthma management. The
      majority of remaining asthma deaths are preventable. Nonetheless, ongoing
      vigilance is required. Asthma remains under-diagnosed and under-treated.
      Childhood asthma has become more common; it is a matter of debate whether it is
      also more severe. Rather than being encouraged by the fall in numbers of asthma
      deaths, we should focus on the surging numbers of children suffering from the
      disease - and the worrying increase in asthma death rates in Australian children 
      and work to avert future issues. 

PMID- 23956968
TI  - Autoerythrocyte sensitization syndrome presenting with general neurodermatitis.
AB  - Autoerythrocyte sensitization syndrome (AES) was first described by Gardner and
      Diamond in 1955, when four women with painful bruising were depicted. Patients
      with AES typically present with the development of recurrent, spontaneous,
      painful ecchymosis, frequently preceded by a prodrome of pain or itching of the
      skin. The patients are sensitive to their own red blood cells injected
      intradermally, and underlying coagulopathies are thought to be absent. We
      introduce a 70-year-old woman presenting with recurrent episodes of painful
      bruising on the trunk and extremities. 

PMID- 23956969
TI  - Elucidation of novel structural scaffold in rohu TLR2 and its binding site
      analysis with peptidoglycan, lipoteichoic acid and zymosan ligands, and
      downstream MyD88 adaptor protein.
AB  - Toll-like receptors (TLRs) play key roles in sensing wide array of microbial
      signatures and induction of innate immunity. TLR2 in fish resembles higher
      eukaryotes by sensing peptidoglycan (PGN) and lipoteichoic acid (LTA) of
      bacterial cell wall and zymosan of yeasts. However, in fish TLR2, no study yet
      describes the ligand binding motifs in the leucine rich repeat regions (LRRs) of
      the extracellular domain (ECD) and important amino acids in TLR2-TIR
      (toll/interleukin-1 receptor) domain that could be engaged in transmitting
      downstream signaling. We predicted these in a commercially important freshwater
      fish species rohu (Labeo rohita) by constructing 3D models of TLR2-ECD, TLR2-TIR,
      and MyD88-TIR by comparative modeling followed by 40 ns (nanosecond) molecular
      dynamics simulation (MDS) for TLR2-ECD and 20 ns MDS for TLR2-TIR and MyD88-TIR.
      Protein (TLR2-ECD)-ligands (PGN, LTA, and zymosan) docking in rohu by
      AutoDock4.0, FlexX2.1, and GOLD4.1 anticipated LRR16-19, LRR12-14, and LRR20-CT
      as the most important ligand binding motifs. Protein (TLR2-TIR)-protein (MyD88
      TIR) interaction by HADDOCK and ZDOCK predicted BB loop, alpha B-helix, alpha C
      helix, and CD loop in TLR2-TIR and BB loop, alpha B-helix, and CD loop in MyD88
      TIR as the critical binding domains. This study provides ligands recognition and
      downstream signaling.

PMID- 23956971
TI  - Total body irradiation with step translation and dynamic field matching.
AB  - The purpose of this study is to develop a total body irradiation technique that
      does not require additional devices or sophisticated processes to overcome the
      space limitation of a small treatment room. The technique aims to deliver a
      uniform dose to the entire body while keeping the lung dose within the tolerance
      level. The technique treats the patient lying on the floor anteriorly and
      posteriorly. For each AP/PA treatment, two complementary fields with dynamic
      field edges are matched over an overlapped region defined by the marks on the
      body surface. A compensator, a spoiler, and lung shielding blocks were used
      during the treatment. Moreover, electron beams were used to further boost the
      chest wall around the lungs. The technique was validated in a RANDO phantom using
      GAFCHROMIC films. Dose ratios at different body sites along the midline ranged
      from 0.945 to 1.076. The dose variation in the AP direction ranged from 96.0% to
      104.6%. The dose distribution in the overlapped region ranged from 98.5% to
      102.8%. Lateral dose profiles at abdomen and head revealed 109.8% and 111.7% high
      doses, respectively, at the body edges. The results confirmed that the technique
      is capable of delivering a uniform dose distribution to the midline of the body
      in a small treatment room while keeping the lung dose within the tolerance level.

PMID- 23956970
TI  - Identification of interconnected markers for T-cell acute lymphoblastic leukemia.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is a complex disease, resulting from
      proliferation of differentially arrested immature T cells. The molecular
      mechanisms and the genes involved in the generation of T-ALL remain largely
      undefined. In this study, we propose a set of genes to differentiate individuals
      with T-ALL from the nonleukemia/healthy ones and genes that are not differential
      themselves but interconnected with highly differentially expressed ones. We
      provide new suggestions for pathways involved in the cause of T-ALL and show that
      network-based classification techniques produce fewer genes with more meaningful
      and successful results than expression-based approaches. We have identified 19
      significant subnetworks, containing 102 genes. The classification/prediction
      accuracies of subnetworks are considerably high, as high as 98%. Subnetworks
      contain 6 nondifferentially expressed genes, which could potentially participate
      in pathogenesis of T-ALL. Although these genes are not differential, they may
      serve as biomarkers if their loss/gain of function contributes to generation of T
      ALL via SNPs. We conclude that transcription factors, zinc-ion-binding proteins,
      and tyrosine kinases are the important protein families to trigger T-ALL. These
      potential disease-causing genes in our subnetworks may serve as biomarkers,
      alternative to the traditional ones used for the diagnosis of T-ALL, and help
      understand the pathogenesis of the disease.

PMID- 23956972
TI  - Probiotics as additives on therapy in allergic airway diseases: a systematic
      review of benefits and risks.
AB  - BACKGROUND: We conducted a systematic review to find out the role of probiotics
      in treatment of allergic airway diseases.   METHODS: A comprehensive search of
      the major electronic databases was done till March 2013. Trials comparing the
      effect of probiotics versus placebo were included. A predefined set of outcome
      measures were assessed. Continuous data were expressed as standardized mean
      difference with 95% CI. Dichotomous data were expressed as odds ratio with 95%
      CI. P value < 0.05 was considered as significant. RESULTS: A total of 12 studies
      were included. Probiotic intake was associated with a significantly improved
      quality of life score in patients with allergic rhinitis (SMD -1.9 (95% CI -3.62,
      -0.19); P = 0.03), though there was a high degree of heterogeneity. No
      improvement in quality of life score was noted in asthmatics. Probiotic intake
      also improved the following parameters: longer time free from episodes of asthma
      and rhinitis and decrease in the number of episodes of rhinitis per year. Adverse
      events were not significant. CONCLUSION: As the current evidence was generated
      from few trials with high degree of heterogeneity, routine use of probiotics as
      an additive on therapy in subjects with allergic airway diseases cannot be
      recommended.

PMID- 23956973
TI  - Hydroxycinnamic acid antioxidants: an electrochemical overview.
AB  - Hydroxycinnamic acids (such as ferulic, caffeic, sinapic, and p-coumaric acids)
      are a group of compounds highly abundant in food that may account for about one
      third of the phenolic compounds in our diet. Hydroxycinnamic acids have gained an
      increasing interest in health because they are known to be potent antioxidants.
      These compounds have been described as chain-breaking antioxidants acting through
      radical scavenging activity, that is related to their hydrogen or electron
      donating capacity and to the ability to delocalize/stabilize the resulting
      phenoxyl radical within their structure. The free radical scavenger ability of
      antioxidants can be predicted from standard one-electron potentials. Thus,
      voltammetric methods have often been applied to characterize a diversity of
      natural and synthetic antioxidants essentially to get an insight into their
      mechanism and also as an important tool for the rational design of new and potent
      antioxidants. The structure-property-activity relationships (SPARs) correlations
      already established for this type of compounds suggest that redox potentials
      could be considered a good measure of antioxidant activity and an accurate
      guideline on the drug discovery and development process. Due to its magnitude in
      the antioxidant field, the electrochemistry of hydroxycinnamic acid-based
      antioxidants is reviewed highlighting the structure-property-activity
      relationships (SPARs) obtained so far.

PMID- 23956974
TI  - Microbial biofilms and breast tissue expanders.
AB  - We previously developed and validated a vortexing-sonication technique for
      detection of biofilm bacteria on the surface of explanted prosthetic joints.
      Herein, we evaluated this technique for diagnosis of infected breast tissue
      expanders and used it to assess colonization of breast tissue expanders. From
      April 2008 to December 2011, we studied 328 breast tissue expanders at Mayo
      Clinic, Rochester, MN, USA. Of seven clinically infected breast tissue expanders,
      six (85.7%) had positive cultures, one of which grew Propionibacterium species.
      Fifty-two of 321 breast tissue expanders (16.2%, 95% CI, 12.3-20.7%) without
      clinical evidence of infection also had positive cultures, 45 growing
      Propionibacterium species and ten coagulase-negative staphylococci. While
      vortexing-sonication can detect clinically infected breast tissue expanders, 16
      percent of breast tissue expanders appear to be asymptomatically colonized with
      normal skin flora, most commonly, Propionibacterium species.

PMID- 23956975
TI  - Detection of the Epstein-Barr virus and DNA-topoisomerase II- alpha in recurrent
      and nonrecurrent giant cell lesion of the jawbones.
AB  - The aims of this study were to determine whether the expression of Topo II-alpha
      correlates with presence of EBV in giant cell lesion of the jawbones and whether
      it is predictive of clinical biologic behavior of these lesions. Paraffin
      embedded tissues from 8 recurrent and 7 nonrecurrent cases of bony GCLs and 9
      peripheral giant cell lesions (PGCLs) as a control group were assessed for the
      expression of EBV and Topo II-alpha using immunohistochemistry. The results
      showed positive staining for Topo II-alpha in mononuclear stromal cells (MSCs)
      and multinucleated giant cells (MGCs). Student t-test showed that mean Topo II
      alpha labelling index (LI) in recurrent cases was significantly higher than that
      in non-recurrent cases (P = 0.0001). Moreover, Spearman's correlation
      coefficients method showed a significant correlation between DNA Topo II-alpha LI
      and both of gender and site in these lesions. Moderate EBV expression in relation
      to the highest Topo II-alpha LI was observed in two cases of GCT. It was
      concluded that high Topo II-alpha LIs could be identified as reliable predicators
      for the clinical behavior of GCLs. Moreover, EBV has no etiological role in the
      benign CGCLs in contrast to its role in the pathogenesis of GCTs.

PMID- 23956976
TI  - Dose verification in intensity modulation radiation therapy: a fractal dimension
      characteristics study.
AB  - PURPOSE: This study describes how to identify the coincidence of desired planning
      isodose curves with film experimental results by using a mathematical fractal
      dimension characteristic method to avoid the errors caused by visual inspection
      in the intensity modulation radiation therapy (IMRT). METHODS AND MATERIALS: The
      isodose curves of the films delivered by linear accelerator according to Plato
      treatment planning system were acquired using Osiris software to aim directly at
      a single interested dose curve for fractal characteristic analysis. The results
      were compared with the corresponding planning desired isodose curves for fractal
      dimension analysis in order to determine the acceptable confidence level between
      the planning and the measurement. RESULTS: The film measured isodose curves and
      computer planning curves were deemed identical in dose distribution if their
      fractal dimensions are within some criteria which suggested that the fractal
      dimension is a unique fingerprint of a curve in checking the planning and film
      measurement results. The dose measured results of the film were presumed to be
      the same if their fractal dimension was within 1%. CONCLUSIONS: This quantitative
      rather than qualitative comparison done by fractal dimension numerical analysis
      helps to decrease the quality assurance errors in IMRT dosimetry verification.

PMID- 23956977
TI  - Uptake of gold nanoparticles in several rat organs after intraperitoneal
      administration in vivo: a fluorescence study.
AB  - BACKGROUND: The gold nanoparticles (GNPs) have potential applications in cancer
      diagnosis and therapy. In an attempt to characterise the potential toxicity or
      hazards of GNPs as a therapeutic or diagnostic tool, the fluorescence spectra in
      several rat organs in vivo were measured after intraperitoneal administration of
      GNPs. METHODS: The experimental rats were divided into control and six groups
      (G1A, G1B, G2A, G2B, G3A, and G3B; G1: 20 nm; G2: 10 nm; G3: 50 nm; A: infusion
      of GNPs for 3 days; B: infusion of GNPs for 7 days). The fluorescence
      measurements were investigated in the liver, kidney, heart, and lung organs of
      rats after intraperitoneal administration of GNPs for periods of 3 and 7 days in
      vivo. RESULTS: The 10 and 20 nm GNPs exhibited spherical morphology shape, while
      the 50 nm GNPs exhibited hexagonal shape. A sharp decrease in the fluorescence
      intensity induced with the larger 50 nm GNPs in the liver, kidney, heart, and
      lung organs of rats at the exposure duration of 3 and 7 days in vivo compared
      with the smaller 10 and 20 nm GNPs was observed. CONCLUSIONS: The decrease in
      fluorescence intensity may be attributed to occurrence of strong quenching,
      decrease in number and surface area of GNPs, and high clearance of GNPs via urine
      and bile. Moreover, decreasing size may lead to an exponential increase in
      surface area relative to volume, thus making GNPs surface more reactive on
      aggregation and to its surrounding biological components. The size, shape,
      surface area, number, and clearance of GNPs play a key role in toxicity and
      accumulation in the different rat organs. This study demonstrates that
      fluorescence peak intensity is particle size and exposure duration dependent.
      This study suggests that fluorescence intensity can be used as a useful tool for
      pointing to bioaccumulation and toxicity induced by GNPs in the different rat
      organs.

PMID- 23956978
TI  - Pharmacokinetic properties and systemic safety of vancomycin-impregnated
      cancellous bone grafts in the treatment of spondylodiscitis.
AB  - The aim of the present study was to investigate the local pharmacokinetic
      properties and the systemic safety of vancomycin-impregnated cancellous bone
      grafts in the treatment of spondylodiscitis. Between 2010 and 2012, 8 patients (5
      females, 3 males, mean age 68.75 y.) were treated with this method. Local
      vancomycin concentrations reached median values of 179 ug/mL (maximum 365 ug/mL)
      on day 1, decreasing to 98 ug/mL on day 3. The urine vancomycin concentrations
      showed similar pharmacokinetic properties as those locally determined. On day 1,
      median values were at 28.05 ug/mL (maximum 287 ug/mL). All serum vancomycin
      concentrations were in all cases and on every day below < 2 ug/mL. The median
      serum creatinine values were preoperatively 0.87 mg/dL, followed by 0.625 mg/dL,
      0.705 mg/dL, and 0.835 mg/dL on day 7, 14, and 28, respectively. No cases of
      ototoxicity could be observed. At a mean follow-up of 16.5 [4-36] months no cases
      of reinfections or persistent infections could be seen. In conclusion, the
      implantation of vancomycin-loaded cancellous bone grafts is an effective option
      in the treatment of spondylodiscitis with a high infection eradication rate and
      no risk of any systemic toxicity. The pharmacokinetic properties can be easily
      monitored locally, in the urine and the serum.

PMID- 23956979
TI  - The possible role of Mena protein and its splicing-derived variants in
      embryogenesis, carcinogenesis, and tumor invasion: a systematic review of the
      literature.
AB  - The Ena/VASP (enabled/vasodilator stimulated phosphoprotein) family includes the
      binding actin proteins such as mammalian Ena (Mena), VASP, and Ena-VASP-like. It
      is known that the perturbation of actin cycle could determine alteration in the
      mobility of cells and in consequence of organogenesis. Few recent studies have
      revealed that Mena protein could play a role in breast or pancreatic
      carcinogenesis. Based on our researches, we observed that the intensity of Mena
      expression increased from premalignant to malignant lesions in some organs such
      as large bowel, stomach, cervix, and salivary glands. These findings prove that
      Mena could be a marker of premalignant epithelial lesions. In premalignant
      lesions, it could be helpful to define more accurately the risk for malignant
      transformation. In malignant tumors, correlation of expression of its splice
      variants could indicate metastatic behavior. In conclusion, we consider that it
      is necessary to analyze the expression of Mena splice variants in a higher number
      of cases, in different epithelial lesions, and also in experimental studies to
      define its exact role in carcinogenesis and also its possible prognostic and
      predictive values.

PMID- 23956980
TI  - Pharmacodynamic effect of clopidogrel in patients undergoing transcatheter aortic
      valve implantation.
AB  - The aim of this study was to analyze periprocedural and mid-term effect of
      clopidogrel on platelet function using the VerifyNow P2Y12 point-of-care assay in
      patients undergoing TAVI. Platelet reactivity was measured at the beginning of
      the procedure after 300 mg clopidogrel bolus administration and during the follow
      up (at 1 month after the procedure) in 52 patients undergoing TAVI using the
      Medtronic CoreValve prosthesis (Medtronic CoreValve). A cutoff value of 240 PRU
      was used to identify nonresponders to clopidogrel treatment with high residual
      platelet reactivity (HRPR). Baseline HRPR was identified in 80% of patients and
      in 72% of patients during 6-month follow-up. There was no significant difference
      in the pharmacodynamic effects of clopidogrel on platelet reactivity from
      baseline to 6-months follow-up (297 +/- 57 vs. 275 +/- 62; P = 0.058). Ischemic
      event occurred only in 3 patients (5.8%) from the study group. In conclusion,
      majority of patients undergoing TAVI had high residual platelet reactivity after
      pretreatment with 300 mg of clopidogrel and during the 6-month follow-up at dual
      antiplatelet treatment. The noneffectiveness of clopidogrel in the TAVI
      population raises the question of the routine use of dual antiplatelet treatment
      in this setting.

PMID- 23956981
TI  - Concerted action of ANP and dopamine D1-receptor to regulate sodium homeostasis
      in nephrotic syndrome.
AB  - The edema formation in nephrotic syndrome (NS) is associated with a blunted
      response to atrial natriuretic peptide (ANP). The natriuretic effects of ANP have
      been related to renal dopamine D1-receptors (D1R). We examined the interaction
      between ANP and renal D1R in rats with puromycin aminonucleoside-induced NS (PAN
      NS). Urinary sodium, cyclic guanosine monophosphate (cGMP) excretion, and D1R
      protein expression and localization in renal tubules were evaluated in PAN-NS and
      control rats before and during volume expansion (VE). The effects of zaprinast
      (phosphodiesterase type 5 inhibitor), alone or in combination with Sch-23390 (D1R
      antagonist), were examined in both groups. The increased natriuresis and urinary
      cGMP excretion evoked by acute VE were blunted in PAN-NS despite increased levels
      of circulating ANP. This was accompanied in PAN-NS by a marked decrease of D1R
      expression in the renal tubules. Infusion of zaprinast in PAN-NS resulted in
      increased urinary excretion of cGMP and sodium to similar levels of control rats
      and increased expression of D1R in the plasma membrane of renal tubular cells.
      Combined administration of Sch-23390 and zaprinast prevented natriuresis and
      increased cGMP excretion induced by zaprinast alone. We conclude that D1R may
      play a major role in the ANP resistance observed in PAN-NS.

PMID- 23956982
TI  - Reduced T cell receptor excision circle levels in the colonic mucosa of
      microscopic colitis patients indicate local proliferation rather than homing of
      peripheral lymphocytes to the inflamed mucosa.
AB  - Dysregulated T cell responses in the intestine may lead to chronic bowel
      inflammation such as collagenous colitis (CC) and lymphocytic colitis (LC),
      together known as microscopic colitis (MC). Having demonstrated increased local T
      cell responses in the intestinal mucosa of MC patients, we investigated the
      recent thymic emigrants by measuring T cell receptor excision circle (TREC)
      levels in the colonic biopsies from CC (n = 8), LC (n = 5), and CC or LC patients
      in histopathological remission (CC-HR, n = 3) (LC-HR, n = 6), non-inflamed
      diarrhoea patients (n = 17), and controls (n = 10) by real-time PCR. We observed
      lower median TREC levels in both CC and LC patients as well as in LC-HR patients
      compared to controls. In contrast to MC patients, non-inflamed diarrhoea patients
      presented with enhanced TREC levels compared to controls. None of the recorded
      differences did, however, reach statistical significance. A trend towards
      increased relative expression of CD3 was noted in all MC subgroups examined and
      reached statistical significance in LC patients compared to controls. In
      conclusion, reduced TRECs level in the colonic mucosa, together with our
      previously demonstrated enhanced expression of Ki67(+) T cells, suggests local
      expansion of resident T lymphocytes in the inflamed mucosa of MC patients.

PMID- 23956983
TI  - Structure-based mechanism for early PLP-mediated steps of rabbit cytosolic serine
      hydroxymethyltransferase reaction.
AB  - Serine hydroxymethyltransferase catalyzes the reversible interconversion of L
      serine and glycine with transfer of one-carbon groups to and from
      tetrahydrofolate. Active site residue Thr254 is known to be involved in the
      transaldimination reaction, a crucial step in the catalytic mechanism of all
      pyridoxal 5'-phosphate- (PLP-) dependent enzymes, which determines binding of
      substrates and release of products. In order to better understand the role of
      Thr254, we have expressed, characterized, and determined the crystal structures
      of rabbit cytosolic serine hydroxymethyltransferase T254A and T254C mutant forms,
      in the absence and presence of substrates. These mutants accumulate a kinetically
      stable gem-diamine intermediate, and their crystal structures show differences in
      the active site with respect to wild type. The kinetic and crystallographic data
      acquired with mutant enzymes permit us to infer that conversion of gem-diamine to
      external aldimine is significantly slowed because intermediates are trapped into
      an anomalous position by a misorientation of the PLP ring, and a new energy
      barrier hampers the transaldimination reaction. This barrier likely arises from
      the loss of the stabilizing hydrogen bond between the hydroxymethyl group of
      Thr254 and the epsilon -amino group of active site Lys257, which stabilizes the
      external aldimine intermediate in wild type SHMTs.

PMID- 23956984
TI  - Sustainability of Tailored Goal Oriented Community Brief Intervention Model among
      risky drinkers in community in Thailand.
AB  - Tailored Goal Oriented Community Brief Intervention Model (TGCBI), first
      implemented as culturally secure and acceptable to communities in Thailand, is
      designed in 2 stages or levels: community level, a culturally secure approach to
      motivate participants to reconsider their drinking behavior; individual level,
      involved in the key messages received from the community level together with
      additional input focused towards individuals. TGCBI's effectiveness was measured
      by the number of abstinent drinkers and number of alcohol-free months among those
      who continued to drink at followup in two communities that originally had high
      prevalence of risky drinking. Multivariate Poisson regression was used to
      investigate the intervention effect. Results indicated that the number of
      participants who stopped drinking 6 months later and the number of alcohol-free
      months during followup were significantly greater (P < 0.05) for 47 participants
      in the intervention group compared to the control group (n = 50). TGCBI results
      in sustainable drinking cessation.

PMID- 23956985
TI  - Anaerobic ammonium oxidation: from laboratory to full-scale application.
AB  - From discovery in the early 1990s to completion of full-scale anammox reactor, it
      took almost two decades to uncover the secret veil of anammox bacteria. There
      were three milestones during the commercialization of anammox: the development of
      the first enrichment culture medium, the completion of the first commercial
      anammox reactor, and the fast start-up of full-scale anammox plant. Till now, the
      culture of anammox bacteria experienced a big progress through two general
      strategies: (a) to start up a reactor from scratch and (b) to seed the reactor
      with enriched anammox sludge. The first full-scale anammox reactor took 3.5 years
      to realize full operation using the first approach due to several reasons besides
      the lack of anammox sludge. On the other hand, the first Asian anammox reactor
      started up in two months, thanks to the availability of anammox seed. Along with
      the implementation of anammox plants, anammox eventually becomes the priority
      choice for ammonium wastewater treatment.

PMID- 23956986
TI  - Does cryopreservation of ovarian tissue affect the distribution and function of
      germinal vesicle oocytes mitochondria?
AB  - The aim of this study was to evaluate mitochondrial alteration and ATP content of
      germinal vesicle (GV) oocytes isolated from fresh and vitrified ovaries. After
      superovulation, the ovaries from adult mice were collected and divided into
      control and vitrified groups. GV oocytes were isolated mechanically from each
      group. Half were cultured for 24 hours and their maturation was assessed.
      Metaphase II oocytes were collected and submitted to in vitro fertilization and
      their fertilization rates and development to the blastocyst stage were evaluated.
      In the remaining GV oocytes, ATP levels were quantified, and mitochondrial
      distribution, mitochondrial membrane potential, and intracellular free calcium
      were detected with rhodamine 123, JC-1 and Flou-4 AM staining, using laser
      scanning confocal microscopy. Maturation and fertilization rates of GV oocytes
      and the developmental rates of subsequent embryos were significantly lower in
      vitrified samples (P < 0.05). The ATP content and Ca(2+) levels differed
      significantly in fresh and vitrified GV oocytes (P < 0.05). Most mitochondria
      were seen as large and homogenous aggregates (66.6%) in fresh GV oocytes compared
      to vitrified oocytes (50%). No significant differences in mitochondrial membrane
      potential were found between the groups. The lower maturation and fertilization
      rates of GV oocytes from vitrified ovaries may be due to changes in their
      mitochondrial function and distribution.

PMID- 23956987
TI  - Characterization of Legionella pneumophila isolated from environmental water and
      ashiyu foot spa.
AB  - Hot springs are the most common infectious source of Legionella pneumophila in
      Japan. However, little is known about the association between L. pneumophila and
      environmental waters other than hot springs. In this study, water samples from 22
      environmental water sites were surveyed; of the 22 samples, five were L.
      pneumophila positive (23%). L. pneumophila was mainly isolated from ashiyu foot
      spas, a type of hot spring for the feet (3/8, 38%). These isolates had genetic
      loci or genes that encoded the virulence factors of L. pneumophila. Moreover,
      these isolates showed higher intracellular growth and stronger cytotoxicity
      compared with the reference strain. These results suggest that ashiyu foot spa
      can be the original source for L. pneumophila infection.

PMID- 23956988
TI  - Behavioral profiles of clinically referred children with intellectual giftedness.
AB  - It is common that intellectually gifted children--that is, children with an IQ >=
      130--are referred to paediatric or child neuropsychiatry clinics for socio
      emotional problems and/or school underachievement or maladjustment. These
      clinically-referred children with intellectual giftedness are thought to
      typically display internalizing problems (i.e., self-focused problems reflecting
      overcontrol of emotion and behavior), and to be more behaviorally impaired when
      "highly" gifted (IQ >= 145) or displaying developmental asynchrony (i.e., a
      heterogeneous developmental pattern, reflected in a significant verbal
      performance discrepancy on IQ tests). We tested all these assumptions in 143
      clinically-referred gifted children aged 8 to 12, using Wechsler's intelligence
      profile and the Child Behavior Checklist. Compared to a normative sample, gifted
      children displayed increased behavioral problems in the whole symptomatic range.
      Internalizing problems did not predominate over externalizing ones (i.e., acted
      out problems, reflecting undercontrol of emotion and behavior), revealing a
      symptomatic nature of behavioral syndromes more severe than expected. "Highly
      gifted" children did not display more behavioral problems than the "low gifted."
      Gifted children with a significant verbal-performance discrepancy displayed more
      externalizing problems and mixed behavioral syndromes than gifted children
      without such a discrepancy. These results suggest that developmental asynchrony
      matters when examining emotional and behavioral problems in gifted children.

PMID- 23956989
TI  - Impairment by sperm agglutinating factor isolated from Escherichia coli: receptor
      specific interactions.
AB  - In an earlier work done in our laboratory, we have been able to isolate a sperm
      agglutinating strain of Escherichia coli from the semen sample of a male
      attending infertility clinic. Further, factor responsible for sperm agglutination
      (SAF) was isolated and purified, and, using SAF as a tool, corresponding SAF
      binding receptor from human spermatozoa has been purified. Characterization of
      SAF and SAF binding receptor using MALDI-TOF showed homology to glutamate
      decarboxylase and MHC class I molecule, respectively. Coincubation of SAF with
      spermatozoa not only resulted in spermagglutination but could also compromise
      other sperm parameters, namely, Mg(2+) dependent ATPase activity and apoptosis.
      Intravaginal administration of SAF could lead to infertility in Balb/c mice. SAF
      induced impairment of sperm parameters, and infertility was observed to be due to
      interaction of SAF with sperm surface receptor component as, when purified
      receptor was introduced, receptor completely inhibited all the detrimental
      effects induced by SAF. From these results, it could be concluded that
      interaction of SAF with spermatozoa is receptor mediated.

PMID- 23956990
TI  - Molecular imaging of nonsmall cell lung carcinomas expressing active mutant EGFR
      kinase using PET with [(124)i]-morpholino-IPQA.
AB  - Mutations in the kinase domain of epidermal growth factor receptor (EGFR) have
      high levels of basal receptor phosphorylation and are associated with clinical
      responsiveness to Iressa in patients with nonsmall cell lung cancer (NSCLC). This
      study aimed to assess the feasibility of morpholino-[(124)I]IPQA derivative as an
      in vivo PET imaging tool for the expression of different EGFR mutants in NSCLC.
      In vitro radiotracer accumulation and washout studies demonstrated a rapid
      accumulation and progressive retention after washout of morpholino-[(131)I]IPQA
      derivative in high EGFR-expressing H1299 NSCLC derivative cell lines (L858R and
      E746-A750 del cell lines), but not in EGFR-transfected H1299 cell line and vector
      transfected H1299 cell line. Using the morpholino-[(124)I]IPQA derivative, we
      obtained noninvasive microPET images of EGFR activity in L858R and E746-A750 del
      subcutaneous tumor xenografts, but not in subcutaneous tumor xenografts grown
      form control cell line. Different EGFR mutant (activity) tumors have a different
      morpholino-[ (*) I]IPQA derivative uptake. However, it still needs to modify the
      structure of IPQA to increase its water solubility and reduce hepatobiliary
      clearance. Morpholino-[(124)I]IPQA derivative may be a potential probe for
      selection of the candidate patients suffering from NSCLC for the small molecule
      tyrosine kinase inhibitor therapy (e.g., Iressa) in the future.

PMID- 23956992
TI  - Peak oxygen uptake responses to training in obese adolescents: a multilevel
      allometric framework to partition the influence of body size and maturity status.
AB  - The influence of body size and maturation on the responses in peak oxygen uptake
      (VO2) to a 12-week aerobic training and nutritional intervention in obese boys (n
      = 30; 10-16 years) was examined using multilevel allometric regressions.
      Anthropometry, sexual maturity status, peak VO2, and body composition were
      measured pre- and postintervention. Significant decrements for body mass, body
      mass index z-score, and waist circumference and increments for stature, fat-free
      mass, and peak oxygen uptake were observed after intervention. Partitioning body
      size on peak VO2, the responses of the individuals to training were positive
      (11.8% to 12.7% for body mass; 7.6% to 8.1% for fat-free mass). Body mass and fat
      free mass were found as significant explanatory variables, with an additional
      positive effect for chronological. The allometric coefficients (k') in the
      initial models were k' = 0.883 and k' = 1.058 for body mass and fat-free mass,
      respectively. The coefficients decreased when age was considered (k' = 0.530 for
      body mass; k' = 0.860 for fat-free mass). Including maturity indicator in the
      models was not significant, thus the influence of variability in sexual maturity
      status in responses to exercise-based intervention in peak VO2 may be mediated by
      the changes in body dimensions.

PMID- 23956993
TI  - Isolation and molecular identification of keratinophilic fungi from public parks
      soil in Shiraz, Iran.
AB  - INTRODUCTION: Keratinophilic fungi are an important group of fungi that live in
      soil. The aim of this study was to isolate and identify keratinophilic fungi from
      the soil of different parks in Shiraz. MATERIALS AND METHODS: A total of 196 soil
      samples from 43 parks were collected. Isolation of the fungi was performed by
      hair bait technique. The isolated colonies were identified by morphologic feature
      of macro- and microconidia and molecular method, using DNA sequence analysis. ITS
      region of ribosomal DNA was amplified and the PCR products were sequenced.
      Results. 411 isolates from 22 genera were identified. Fusarium (23.8%),
      Chrysosporium (13.13%), Acremonium (12.65%), Penicillium (12.39%), Microsporum
      gypseum (1.94%), Bionectria ochroleuca (1.21%), Bipolaris spicifera (1.21%),
      Scedosporium apiospermum (0.82%), Phialophora reptans (0.82%), Cephalosporium
      curtipes (0.49%), Scedosporium dehoogii (0.24%), Ochroconis constricta (0.24%),
      Nectria mauritiicola (0.49%), Chaetomium (0.49%), Scopulariopsis (0.24%),
      Malbranchea (0.24%), and Tritirachium (0.24%) were the most important isolates.
      Most of the fungi were isolated from the soils with the PH range of 7 to 8.
      CONCLUSION: Our study results showed that many keratinophilic fungi isolated from
      the parks soil are important for public health and children are an important
      group at a high risk of being exposed to these fungi.

PMID- 23956991
TI  - Metabolic factors and chronic hepatitis C: a complex interplay.
AB  - In the last years, several lines of evidence showed how metabolic factors may
      influence the natural history of patients with chronic hepatitis C. Chronic HCV
      infection is able to perturb the metabolic homeostasis of the host, in a context
      of complex interactions where pre-existent metabolic status and genetic
      background play an important role, allowing us to state that HCV infection is a
      systemic disease. In this review, we discuss the most recent lines of evidence on
      the main metabolic factors that are known to be associated with CHC, namely,
      insulin resistance/type 2 diabetes, steatosis, visceral obesity, atherosclerosis,
      vitamin D, menopause, fructose and coffee intake, lipoproteins,
      methylenetetrahydrofolate reductase status, and hyperuricaemia. In particular, we
      focus on the pathophysiological mechanisms underlying the correlation between HCV
      infection and metabolic disorders, the impact of metabolic factors on the
      progression of liver and non-liver-related diseases, and, on the contrary, the
      possible influence of chronic HCV infection on metabolic features. In this
      setting, the importance of a multifaceted evaluation of CHC patients and a prompt
      correction of modifiable metabolic risk factors should be emphasized.

PMID- 23956994
TI  - Bilastine: a new nonsedating oral H1 antihistamine for treatment of allergic
      rhinoconjunctivitis and urticaria.
AB  - Bilastine is a new, well-tolerated, nonsedating H1 receptor antihistamine. In the
      fasting state bilastine is quickly absorbed, but the absorption is slowed when it
      is taken with food or fruit juice. Therefore, it is recommended that bilastine is
      taken at least one hour before and no sooner than two hours after a meal.
      Clinical studies sponsored by the manufacturer have shown that bilastine 20 mg
      once daily is as efficacious as other nonsedating antihistamines in allergic
      rhinoconjunctivitis and chronic urticaria in individuals from 12 and 18 years of
      age, respectively. Bilastine is efficacious in all nasal symptoms including
      obstruction and in eye symptoms. The observations indicate that non-sedating
      antihistamines, as opposed to what has been thought previously, may be helpful in
      patients with allergic rhinitis in whom nasal obstruction is a major concern.
      Current international guidelines need to be revised in the light of the recent
      evidence. Research into aspects of pharmacokinetics and efficacy and adverse
      effect profiles of bilastine in children under 12 years of age is needed as are
      dose-response assessments and studies planned rigorously with the aim of
      assessing quality of life effects.

PMID- 23956996
TI  - Bovine papillomavirus clastogenic effect analyzed in comet assay.
AB  - Bovine papillomavirus (BPV) is an oncogenic virus related to serious livestock
      diseases. Oncoproteins encoded by BPV are involved in several steps of cellular
      transformation and have been reported as presenting clastogenic effects in
      peripheral lymphocytes and primary culture cells. The aim of this study was to
      evaluate the clastogenic potential of BPV types 1, 2, and 4 by comet assay.
      Peripheral blood was collected from 37 bovines, 32 infected with different levels
      of papillomatosis (12 animals have no affection) and five calves, virus free
      (negative control). The viral identification showed presence of more than one
      virus type in 59.375% of the infected animals. Comet assay was performed
      according to alkaline technique. The Kruskal-Wallis test showed statistical
      difference between the negative control group and infected animals (P = 0.0015).
      The Dunn post hoc test showed difference comparing the infected animals with
      calves. Mann-Whitney U test verified no difference between animals infected with
      only one viral type and animals presenting more than one viral type. The comet
      assay is considered an efficient tool for assessment of damage in the host
      chromatin due to viral action, specifically highlighting viral activity in blood
      cells.

PMID- 23956997
TI  - Protein homeostasis defects of alanine-glyoxylate aminotransferase: new
      therapeutic strategies in primary hyperoxaluria type I.
AB  - Alanine-glyoxylate aminotransferase catalyzes the transamination between L
      alanine and glyoxylate to produce pyruvate and glycine using pyridoxal 5'
      phosphate (PLP) as cofactor. Human alanine-glyoxylate aminotransferase is a
      peroxisomal enzyme expressed in the hepatocytes, the main site of glyoxylate
      detoxification. Its deficit causes primary hyperoxaluria type I, a rare but
      severe inborn error of metabolism. Single amino acid changes are the main type of
      mutation causing this disease, and considerable effort has been dedicated to the
      understanding of the molecular consequences of such missense mutations. In this
      review, we summarize the role of protein homeostasis in the basic mechanisms of
      primary hyperoxaluria. Intrinsic physicochemical properties of polypeptide chains
      such as thermodynamic stability, folding, unfolding, and misfolding rates as well
      as the interaction of different folding states with protein homeostasis networks
      are essential to understand this disease. The view presented has important
      implications for the development of new therapeutic strategies based on targeting
      specific elements of alanine-glyoxylate aminotransferase homeostasis.

PMID- 23956998
TI  - Autophagy and human parturition: evaluation of LC3 expression in placenta from
      spontaneous or medically induced onset of labor.
AB  - Induction of labor is one of the most used procedures in obstetrics, performed to
      achieve vaginal delivery through cervical ripening and stimulation of uterine
      contractions. We investigated the impact of induction of labor upon placental
      autophagy, a catabolic pathway activated in response to alteration of the
      physiological intracellular conditions. We collected 28 singleton placentas at
      the time of uncomplicated term vaginal delivery (7 spontaneous onset of labor, 21
      induced labor). Autophagy was evaluated by immunohistochemistry,
      immunofluorescence, and immunoblotting. No significant difference in the
      autophagy expression was found between spontaneous or induced onset of labor. We
      found an inverse relationship between autophagy expression and the maternal
      prepregnancy body mass index, irrespective of the mode of labor onset. This
      result could be related to the nutritional maternal habits before and throughout
      pregnancy rather than rapid metabolic changes during labor.

PMID- 23956999
TI  - The stepwise behavioral responses: behavioral adjustment of the Chinese rare
      minnow (Gobiocypris rarus) in the exposure of carbamate pesticides.
AB  - In order to illustrate the behavioral regulation in environmental stress, the
      behavioral responses of the Chinese rare minnow (Gobiocypris rarus) to arprocarb,
      carbofuran, and oxamyl were analyzed with an online monitoring system. The Self
      Organizing Map (SOM) was used to define the patterns of the behavioral data
      obtained from treatments at concentrations of 0.1 toxic unit (TU), 1 TU, 2 TU, 5
      TU, 10 TU, and 20 TU and a control. In certain cases, differences among the
      carbamate pesticides (CPs) tested were observed. The profiles of behavioral
      strength (BS) in SOM varied according to the concentration used. The time of the
      first significant decrease of the BS varied inversely with the CP concentrations.
      The results suggested that the behavioral regulation in the stepwise behavioral
      responses (SBR) was evident. The primary movement behaviors shown by the SBR
      model included no effect, stimulation, acclimation, adjustment (readjustment),
      and toxic effect, especially at the lower concentrations. However, higher stress
      (10 TU and 20 TU) might limit the function of the behavioral adjustment produced
      by the intrinsic response mechanisms. It was concluded that SBR, which were
      affected by both the concentration and the exposure time, could be used as a
      suitable indicator in the ecotoxicological risk assessment of CPs.

PMID- 23957000
TI  - Experimental susceptibility of gilthead sea bream, Sparus aurata, via challenge
      with Anisakis pegreffii larvae.
AB  - The endoscopic and histopathological findings detected in Sparus aurata
      experimentally infected with third-stage Anisakis larvae without intermediate
      host are evaluated and discussed. In six fish, live nematode larvae were
      introduced by gastroscopy into the stomach. The first observation by endoscope,
      15 days after challenge, showed the presence of some larvae at the level of
      gastric mucosa. An explorative celioscopy, performed 60 days after challenge,
      showed haemorrhages and/or nodules on the gut of two fishes. Necropsy and
      histology demonstrated parasites in the context of the tissue changes. The
      finding of live nematode larvae as well as the evidence of tissue change confirm
      the experimental susceptibility of gilthead sea bream towards Anisakis. 

PMID- 23957002
TI  - Pain coping strategies for children with arthritis.
AB  - OBJECTIVE: To present information on pain management strategies for children with
      juvenile idiopathic arthritis (JIA). METHODS: The second author developed a
      manual to present pain management strategies to children. The use of the manual
      was pilot-tested with a group of children with JIA. Telephone interviews were
      used to gather information on implementation of pain management strategies.
      RESULTS: Children were able to implement the pain management strategies. Children
      reported a reduction in daily pain experiences related to JIA when using the pain
      management strategies. CONCLUSIONS: The pain management strategies were
      successful as an adjunctive intervention for short-term pain management. Pain
      symptoms related to JIA can severely limit children's participation in daily
      activities. Further study on how children use pain management strategies to
      improve their involvement in daily activities will provide useful clinical
      information.

PMID- 23957001
TI  - Antioxidant and alpha -amylase inhibitory property of phyllanthus virgatus L.: an
      in vitro and molecular interaction study.
AB  - The present study on Phyllanthus virgatus, known traditionally for its remedial
      potential, for the first time provides descriptions of the antioxidant and
      inhibition of alpha -amylase enzyme activity first by in vitro analyses, followed
      by a confirmatory in silico study to create a stronger biochemical rationale. Our
      results illustrated that P. virgatus methanol extract exhibited strong
      antioxidant and oxidative DNA damage protective activity than other extracts,
      which was well correlated with its total phenolic content. In addition, P.
      virgatus methanol extract strongly inhibited the alpha -amylase activity (IC50
      33.20 +/- 0.556  MU g/mL), in a noncompetitive manner, than acarbose (IC50 76.88
      +/- 0.277  MU g/mL), which showed competitive inhibition. Moreover, this extract
      stimulated the glucose uptake activity in 3T3-L1 cells and also showed a good
      correlation between antioxidant and alpha -amylase activities. The molecular
      docking studies of the major bioactive compounds (9,12-octadecadienoic acid,
      asarone, 11-octadecenoic acid, and acrylic acid) revealed via GC-MS analysis from
      this extract mechanistically suggested that the inhibitory property may be due to
      the synergistic effect of these bioactive compounds. These results provide
      substantial basis for the future use of P. virgatus methanol extract and its
      bioactive compound in in vivo system for the treatment and management of diabetes
      as well as in the related condition of oxidative stress.

PMID- 23957003
TI  - Effects of sheep and mouse urine on the growth pattern of Leishmania major
      promastigotes.
AB  - The protozoan parasites of the genus Leishmania are the causative agents of
      different clinical diseases. Fetal calf serum (FCS) is the main part and the most
      expensive ingredient of the Leishmania culture media. Here, the efficacies of
      different concentrations (1%, 2.5%, 5%, and 10%) of the filtered and autoclaved
      sheep and mouse urine were evaluated as a growth stimulator in Leishmania culture
      procedure. The results indicated that culture media enriched with the filtered
      sheep and mouse urine supported the growth of the parasites and can be used for
      cultivation of Leishmania parasites. In conclusion, this study has demonstrated
      an alternative low-cost medium that could be used in cultivation process of
      Leishmania major promastigotes.

PMID- 23957004
TI  - Analytical variables affecting analysis of F2-isoprostanes and F4-neuroprostanes
      in human cerebrospinal fluid by gas chromatography/mass spectrometry.
AB  - F2-isoprostanes (F2-IsoPs) are a gold marker of lipid peroxidation in vivo,
      whereas F4-neuroprostanes (F4-NPs) measured in cerebrospinal fluid (CSF) or brain
      tissue selectively indicate neuronal oxidative damage. Gas
      chromatography/negative-ion chemical-ionization mass spectrometry (GC/NICI-MS) is
      the most sensitive and robust method for quantifying these compounds, which is
      essential for CSF samples because abundance of these compounds in CSF is very
      low. The present study revealed potential interferences on the analysis of F2
      IsoPs and F4-NPs in CSF by GC/NICI-MS due to the use of improper analytical
      methods that have been employed in the literature. First, simultaneous
      quantification of F2-IsoPs and F4-NPs in CSF samples processed for F4-NPs
      analysis could cause poor chromatographic separation and falsely higher F2-IsoPs
      values for CSF samples with high levels of F2-IsoPs and F4-NPs. Second, retention
      of unknown substances in GC columns from CSF samples during F4-NPs analysis and
      from plasma samples during F2-IsoPs analysis might interfere with F4-NPs analysis
      of subsequent runs, which could be solved by holding columns at a high
      temperature for a period of time after data acquisition. Therefore, these special
      issues should be taken into consideration when performing analysis of F2-IsoPs
      and F4-NPs in CSF to avoid misleading results.

PMID- 23957005
TI  - Normative findings for periocular anthropometric measurements among Chinese young
      adults in Hong Kong.
AB  - Measurement of periocular structures is of value in several clinical specialties
      including ophthalmology, optometry, medical and clinical genetics, oculoplastic
      surgery, and traumatology. Therefore we aimed to determine the periocular
      anthropometric norms for Chinese young adults using a noninvasive 3D
      stereophotography system. Craniofacial images using the 3dMDface system were
      acquired for 103 Chinese subjects (51 males and 52 females) between the ages of
      18 and 35 years. Anthropometric landmarks were identified on these digital images
      according to standard definitions, and linear distances between these landmarks
      were calculated. It was found that ocular measurements were significantly larger
      in Chinese males than females for intercanthal width, biocular width, and eye
      fissure lengths. No gender differences were found in the eye fissure height and
      the canthal index which ranged between 43 and 44. Both right and left eye fissure
      height-length ratios were significantly larger in females. This is the first
      study to employ 3D stereophotogrammetry to create a database of anthropometric
      normative data for periocular measurements. These data would be useful for
      clinical interpretation of periocular pathology and serve as reference values
      when planning aesthetic and posttraumatic surgical interventions.

PMID- 23957006
TI  - Microbial inoculants and their impact on soil microbial communities: a review.
AB  - The knowledge of the survival of inoculated fungal and bacterial strains in field
      and the effects of their release on the indigenous microbial communities has been
      of great interest since the practical use of selected natural or genetically
      modified microorganisms has been developed. Soil inoculation or seed
      bacterization may lead to changes in the structure of the indigenous microbial
      communities, which is important with regard to the safety of introduction of
      microbes into the environment. Many reports indicate that application of
      microbial inoculants can influence, at least temporarily, the resident microbial
      communities. However, the major concern remains regarding how the impact on
      taxonomic groups can be related to effects on functional capabilities of the soil
      microbial communities. These changes could be the result of direct effects
      resulting from trophic competitions and antagonistic/synergic interactions with
      the resident microbial populations, or indirect effects mediated by enhanced root
      growth and exudation. Combination of inoculants will not necessarily produce an
      additive or synergic effect, but rather a competitive process. The extent of the
      inoculation impact on the subsequent crops in relation to the buffering capacity
      of the plant-soil-biota is still not well documented and should be the focus of
      future research.

PMID- 23957007
TI  - Identification and characterization of cyclic AMP response element-binding
      protein H response element in the human apolipoprotein A5 gene promoter.
AB  - The cyclic AMP response element-binding protein H (CREBH) plays important roles
      in hepatic lipogenesis, fatty acid oxidation, and lipolysis under metabolic
      stress. Here, we report CREBH as a novel regulator of human APOA5. Knockdown of
      endogenous CREBH expression via small interfering RNA resulted in the
      downregulation of human APOA5 mRNA expression in human hepatoma cells, HepG2.
      Sequence analysis suggested that putative CREBH response element (CREBHRE) is
      located in the human APOA5 promoter region and is highly conserved in both human
      and rodent. To clarify whether the human APOA5 promoter is regulated by CREBH, we
      analyzed the human APOA5 promoter region using a transient transfection assay and
      determined that transfection of CREBH induced human APOA5 promoter activity.
      Moreover, it was shown that CREBH directly regulated human APOA5 gene expression
      by binding to a unique CREBHRE located in the proximal human APOA5 promoter
      region, using 5'-deletion and mutagenesis of human APOA5 promoter analysis and
      chromatin immunoprecipitation assay. Taken together, our results demonstrated
      that human APOA5 is directly regulated by CREBH via CREBHRE and provided a new
      insight into the role of this liver-specific bZIP transcription factor in
      lipoprotein metabolism and triglyceride homeostasis.

PMID- 23957009
TI  - miR-1279, miR-548j, miR-548m, and miR-548d-5p binding sites in CDSs of paralogous
      and orthologous PTPN12, MSH6, and ZEB1 Genes.
AB  - Only PTPN12, MSH6, and ZEB1 have significant miR-1279 binding sites among
      paralogous genes of human tyrosine phosphatase family, DNA mismatch repair
      family, and zinc finger family, respectively. All miRNA binding sites are located
      within CDSs of studied mRNAs. Nucleotide sequences of hsa-miR-1279 binding sites
      with mRNAs of human PTPN12, MSH6, and ZEB1 genes encode TKEQYE, EGSSDE, and
      GEKPYE oligopeptides, respectively. The conservation of miRNA binding sites
      encoding oligopeptides has been revealed. MRNAs of many paralogs of zinc finger
      gene family have from 1 to 12 binding sites coding the same GEKPYE hexapeptide.
      MRNAs of PTPN12, MSH6, and ZEB1 orthologous genes from different animal species
      have binding sites for hsa-miR-1279 which consist of homologous oligonucleotides
      encoding similar human oligopeptides TKEQYE, EGSSDE, and GEKPYE. MiR-548j, miR
      548m, and miR-548d-5p have homologous binding sites in the mRNA of PTPN12
      orthologous genes which encode PRTRSC, TEATDI, and STASAT oligopeptides,
      respectively. All regions of miRNA are important for binding with the mRNA.

PMID- 23957008
TI  - Translational bioinformatics for diagnostic and prognostic prediction of prostate
      cancer in the next-generation sequencing era.
AB  - The discovery of prostate cancer biomarkers has been boosted by the advent of
      next-generation sequencing (NGS) technologies. Nevertheless, many challenges
      still exist in exploiting the flood of sequence data and translating them into
      routine diagnostics and prognosis of prostate cancer. Here we review the recent
      developments in prostate cancer biomarkers by high throughput sequencing
      technologies. We highlight some fundamental issues of translational
      bioinformatics and the potential use of cloud computing in NGS data processing
      for the improvement of prostate cancer treatment.

PMID- 23957010
TI  - Cytogenetic abnormality in exfoliated cells of buccal mucosa in head and neck
      cancer patients in the Tunisian population: impact of different exposure sources.
AB  - Chromosome/DNA instability could be one of the primary causes of malignant cell
      transformation. The objective of the present study was to evaluate the
      spontaneous genetic damages in exfoliated cells of buccal mucosa of head and neck
      cancer (HNC) by counting micronucleus (MN) and binucleated (BN) cells
      frequencies. MN and BN frequencies were significantly increased in HNC patients
      compared with controls (5.53 +/- 3.09/1000 cells, 5.63 +/- 2.99/1000 cells versus
      2.36 +/- 2.11/1000 cells, 3.09 +/- 1.82/1000 cells, P < 0.001). Regarding the
      gender and the age, the frequencies of the MN and BN were significantly higher
      than those of controls (P < 0.01). The evaluation of the MN and BN frequencies
      revealed a significant increase (P < 0.001) in the cases in relation to the
      control group after controlling the risk factors (tobacco smoking and chewing and
      occupational exposure) of HNC. Moreover, MN and BN frequencies were significantly
      increased in smokers and chewers compared with nonsmokers and nonchewers among
      patients (P < 0.05). MN frequency was significantly (P = 0.014) different between
      patients occupationally exposed (6.99 +/- 3.40/1000 cells) and nonexposed (4.70
      +/- 2.48/1000 cells) among HNC group. The logistic regression model illustrated
      that HNC was significantly associated with frequencies of MN (OR = 8.63, P <
      0.0001) and BN (OR = 5.62, P = 0.001). Our results suggest that increased
      chromosome/DNA instabilities may be associated with HNC.

PMID- 23957011
TI  - Robust cell size checkpoint from spatiotemporal positive feedback loop in fission
      yeast.
AB  - Cells must maintain appropriate cell size during proliferation. Size control may
      be regulated by a size checkpoint that couples cell size to cell division.
      Biological experimental data suggests that the cell size is coupled to the cell
      cycle in two ways: the rates of protein synthesis and the cell polarity protein
      kinase Pom1 provide spatial information that is used to regulate mitosis
      inhibitor Wee1. Here a mathematical model involving these spatiotemporal
      regulations was developed and used to explore the mechanisms underlying the size
      checkpoint in fission yeast. Bifurcation analysis shows that when the
      spatiotemporal regulation is coupled to the positive feedback loops (active Cdc2
      promotes its activator, Cdc25, and suppress its inhibitor, Wee1), the mitosis
      promoting factor (MPF) exhibits a bistable steady-state relationship with the
      cell size. The switch-like response from the positive feedback loops naturally
      generates the cell size checkpoint. Further analysis indicated that the spatial
      regulation provided by Pom1 enhances the robustness of the size checkpoint in
      fission yeast. This was consistent with experimental data.

PMID- 23957012
TI  - Cardiac contractile reserve parameters are related to prognosis in septic shock.
AB  - INTRODUCTION: Cardiac reserve could be defined as the spontaneous magnitude from
      basal to maximal cardiac power under stress conditions. The aim of this study was
      to evaluate the prognostic value of cardiac reserve parameters in resuscitated
      septic shock patients. METHODS: Seventy patients with septic shock were included
      in a prospective and observational study. Prior to inclusion, patients were
      resuscitated to reach a mean arterial pressure of 65-75 mmHg with an euvolemic
      status. General, hemodynamic, and cardiac reserve-related parameters (cardiac
      index, double product, and cardiac power index) were collected at inclusion and
      at day 1. RESULTS: Seventy patients were included with 28-day mortality at 38.5%.
      Ten of the 70 patients died during the first day. In multivariate analysis,
      independent predictors of death were SAPS II >= 58 (OR: 3.36 [1.11-10.17]; P =
      0.032), a high double product at inclusion (OR [95% IC]: 1.20 [1.00-1.45] per
      10(3) mmHg . min; P = 0.047), and at day 1, a decrease in cardiac index (1.30
      [1.08-1.56] per 0.5 L/min/m(2); P = 0.007) or cardiac power index (1.84 [1.18
      2.87] per 0.1 W/m(2), P = 0.008). CONCLUSION: In the first 24 hours, parameters
      related to cardiac reserve, such as double product and cardiac index evolution,
      provide crucial and easy to achieve hemodynamic physiological information, which
      may impact the outcome.

PMID- 23957013
TI  - Effects of Nigella sativa and Lepidium sativum on cyclosporine pharmacokinetics.
AB  - The present study was conducted to investigate the effects of Nigella sativa and
      Lepidium sativum on the pharmacokinetics of cyclosporine in rabbits. Two groups
      of animals were treated separately with Nigella sativa (200 mg/kg p.o.) or
      Lepidium sativum (150 mg/kg p.o.) for eight consecutive days. On the 8th day,
      cyclosporine (30 mg/kg p.o.) was administered to each group one hour after herbal
      treatment. Blood samples were withdrawn at different time intervals (0.0, 0.5,
      1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12, and 24 hrs) from marginal ear vein.
      Cyclosporine was analyzed using UPLC/MS method. The coadministration of Nigella
      sativa significantly decreased the C(max) and AUC(0-infinity) of cyclosporine;
      the change was observed by 35.5% and 55.9%, respectively (P <= 0.05). Lepidium
      sativum did not produce any significant change in C(max) of cyclosporine,
      although its absorption was significantly delayed compared with control group. A
      remarkable change was observed in T(max) and AUC(0-t) of Lepidium sativum treated
      group. Our findings suggest that concurrent consumption of Nigella sativa and
      Lepidium sativum could alter the pharmacokinetics of cyclosporine at various
      levels.

PMID- 23957014
TI  - Factors associated with HIV/AIDS in Sudan.
AB  - OBJECTIVES: To assess participants' knowledge about HIV/AIDS and to identify the
      factors associated with HIV/AIDS in Sudan. METHODS: Observational cross-sectional
      study carried out at Omdurman National Voluntary Counseling and Testing Centre,
      Sudan covered 870 participants. Sociodemographic data as well as information
      related to sexual behavior were collected. RESULTS: Most of the respondents were
      knowledgeable about the true transmission modes for AIDS virus. Very few
      respondents knew someone infected with AIDS (4.5%), died of AIDS (8.1%), accepted
      to live with someone infected with AIDS (4.7%) or to work with someone infected
      with AIDS (2.1%). Regarding sexual behavior, 96.5% had reported their first
      sexual experience between 20 and 30 years, with 85.7% reporting one or two
      partners, and only 1.8% reported using condom. Multivariate logistic regression
      showed that circumcision, religion, marital status, age at first sex, number of
      sexual partners, education level, and misconception of knowledge are the main
      risk factors associated with HIV/AIDS. CONCLUSION: Our results showed that a
      number of diversity risk factors were associated with HIV/AIDS. It is unlikely
      that a holistic approach will be found to immediately change sexual-risk-relating
      behavior. Interventions including sustained educational programs, promotion of
      condom, and encouragement of voluntary testing and active involvement of the
      country's political and religious leaders will be needed to alleviate this
      problem.

PMID- 23957015
TI  - The role of adrenomedullin in the renal NADPH oxidase and (pro)renin in diabetic
      mice.
AB  - Adrenomedullin has an antioxidative action and protects organs in various
      diseases. To clarify the role of adrenomedullin in diabetic nephropathy, we
      investigated the NADPH oxidase expression, renin-secreting granular cell (GC)
      hyperplasia, and glomerular matrix expansion in the streptozotocin (STZ)-induced
      diabetic adrenomedullin gene knockout (AMKO) mice compared with the STZ-diabetic
      wild mice at 10 weeks. The NADPH oxidase p47phox expression and lipid
      peroxidation products were enhanced in the glomeruli of the diabetic mice
      compared with that observed in the controls in both wild and AMKO mice. These
      changes were more obvious in the AMKO mice than in the wild mice. Glomerular
      mesangial matrix expansion was more severe in the diabetic AMKO mice than in the
      diabetic wild mice and exhibited a positive correlation with the degree of lipid
      peroxidation products in the glomeruli. Proteinuria was significantly higher in
      the diabetic AMKO mice than in the diabetic wild mice. The GC hyperplasia score
      and the renal prorenin expression were significantly increased in the diabetic
      AMKO mice than in the diabetic wild mice, and a positive correlation was observed
      with the NADPH oxidase expression in the macula densa. The endogenous
      adrenomedullin gene exhibits an antioxidant action via the inhibition of NADPH
      oxidase probably by suppressing the local renin-angiotensin system. 

PMID- 23957016
TI  - A Novel non-sense Mutation in Keratin 10 Causes a Familial Case of Recessive
      Epidermolytic Ichthyosis.
AB  - Epidermolytic ichthyosis (EI) is a rare skin disorder characterized by
      generalized erythroderma and cutaneous blistering at birth, which is substituted
      by hyperkeratosis later in life. It is caused by autosomal dominant mutations in
      highly conserved regions of KRT1 and KRT10. To date, only 4 mutations with
      autosomal recessive inheritance of EI have been described in consanguineous
      families. All of them affect the 2B domain of KRT10. In the present study we
      describe four patients with EI (including one lethal case) born from unaffected
      parents in a consanguineous family of a native Venezuelan community. The
      objective of this study was to characterize the clinical, genetic and
      morphological aspects of the disease in this family, as well as understand its
      functional implications. Genomic DNA was sequenced for KRT10 and KRT1.
      Immunofluoresence for keratin expression was performed on cutaneous biopsies.
      After examination of cutaneous biopsies histology, our results showed
      hyperkeratosis and acantholysis with an expanded granular layer. Sequencing of
      KRT10 demonstrated a non-sense mutation (p.Tyr282Ter.) corresponding to the 1B
      domain of the protein in patients and a heterozygous pattern in other family
      members, resulting in complete absence of K10. The loss of K10 was compensated by
      upregulation of K14 and K17. In conclusion, this novel mutation in KRT10 is the
      first recessive genetic variation that is not located in the so called "hot spot"
      for recessive EI, suggesting that other areas of the gene are also susceptible
      for such mutations.

PMID- 23957017
TI  - Effects of Promoting Health Among Teens on Dietary, Physical Activity and
      Substance Use Knowledge and Behaviors for African American Adolescents.
AB  - BACKGROUND: African Americans are disproportionately affected by cardiovascular
      disease and cancer. Health promotion interventions hold promise for reducing
      health disparities. PURPOSE: Promoting Health Among Teens (PHAT) is a brief,
      culturally tailored health education intervention to decrease cardiovascular
      disease and cancer risk for African Americans. This study evaluated the effects
      of PHAT for African American adolescents ages 14 to 17 in four eastern cities in
      the USA. METHODS: A randomized controlled design (N = 1,654) was used to
      determine differences in health knowledge, diet, physical activity, and substance
      use behaviors between PHAT participants and a sexual health promotion control
      group. Data were collected at baseline, three, six, and twelve months post
      intervention. Growth curve modeling was used to detect differences in health
      knowledge, dietary behaviors, physical activity, and substance use between PHAT
      and control group participants. RESULTS: PHAT participants had significantly
      greater knowledge gains but modest behavior changes compared to control group
      participants. DISCUSSION: PHAT is a promising intervention to increase knowledge
      and address selected health behaviors in African American youth. TRANSLATION TO
      HEALTH EDUCATION PRACTICE: Future attempts to execute PHAT should continue its
      emphasis on knowledge building while increasing intervention dosage and modifying
      length of time for intervention sessions.

PMID- 23957018
TI  - What constitutes a clinically important pain reduction in patients after third
      molar surgery?
AB  - BACKGROUND: For patients with surgical third molar removal, it is unknown what
      constitutes a clinically important change in patients' visual analogue scale
      (VAS) reports of pain intensity. OBJECTIVES: To determine what constitutes a
      clinically important change in pain intensity on a VAS following surgical removal
      of the third molar. METHODS: The study population consisted of patients
      participating in three randomized trials. Patients were asked to rate their pain
      three times per day over a period of seven days on a 100 mm VAS after surgical
      removal of the third molar. Global Perceived Effect was measured on day 1 and day
      7 and was used as the external criterion for assessing clinically important pain
      reduction. Global Perceived Effect scores of 6 ('much improved') or higher were
      classified as clinically 'successful', and scores of 5 ('slightly improved') or
      below were classified as clinically 'unsuccessful'. For each trial, the mean
      absolute and relative changes in VAS scores were calculated for both 'successful'
      and 'unsuccessful' treatments. Sensitivity and specificity analyses were
      performed. RESULTS: The patients who reported 'successful' pain reduction showed
      a relative pain reduction of >=69% and an absolute pain reduction >2.5 cm on the
      VAS, whereas patients who classified their pain reduction as 'unsuccessful' had a
      relative pain reduction of <=18.5% and an absolute pain reduction <0.5 cm on the
      VAS. Furthermore, sensitivity and specificity analyses showed that a cut-off
      point of >=50% relative pain reduction exhibited the best balance of sensitivity
      and specificity. CONCLUSION: Relative pain reduction of >=50% and an absolute
      pain reduction of >=2.5 cm on the VAS were most accurate in predicting a
      successful pain reduction after a given treatment.

PMID- 23957019
TI  - Cancer-related pain in older adults receiving palliative care: patient and family
      caregiver perspectives on the experience of pain.
AB  - BACKGROUND: Despite an emphasis on pain management in palliative care, pain
      continues to be a common problem for individuals with advanced cancer. Many of
      those affected are older due to the disproportionate incidence of cancer in this
      age group. There remains little understanding of how older patients and their
      family caregivers perceive patients' cancer-related pain, despite its
      significance for pain management in the home setting. OBJECTIVES: To explore and
      describe the cancer pain perceptions and experiences of older adults with
      advanced cancer and their family caregivers. METHODS: A qualitative descriptive
      approach was used to describe and interpret data collected from semistructured
      interviews with 18 patients (>=65 years of age) with advanced cancer receiving
      palliative care at home and their family caregivers. RESULTS: The main category
      'Experiencing cancer pain' incorporated three themes. The theme 'Feeling cancer
      pain' included the sensory aspects of the pain, its origin and meanings
      attributed to the pain. A second theme, 'Reacting to cancer pain', included
      patients' and family caregivers' behavioural, cognitive (ie, attitudes, beliefs
      and control) and emotional responses to the pain. A third theme, 'Living with
      cancer pain' incorporated individual and social-relational changes that resulted
      from living with cancer pain. CONCLUSIONS: The findings provide an awareness of
      cancer pain experienced by older patients and their family caregivers within the
      wider context of ongoing relationships, increased patient morbidity and other
      losses common in the aged.

PMID- 23957020
TI  - Peripheral interleukin-1beta levels are elevated in chronic tension-type headache
      patients.
AB  - BACKGROUND: Tension-type headache is the most common form of headache and its
      chronic form, chronic tension-type headache (CTTH), is one of the most difficult
      to treat. The etiology of CTTH is not well understood, but is believed to be
      multifactorial and to vary among individuals. In the present study, the authors
      sought to identify common mechanisms of CTTH pathology. Empirical studies have
      implicated various immunomodulatory cytokines as mediators of chronic pain
      disorders, including CTTH. OBJECTIVES: To determine the role of peripheral
      cytokines and genetic factors in the development of CTTH. METHODS: A panel of
      cytokines hypothesized to play a role in the pathogenesis of CTTH was measured
      using cytometric bead arrays and ELISAs in 56 individuals with CTTH and 42
      healthy control participants between 18 and 65 years of age. RESULTS: Levels of
      interleukin (IL)-1beta were significantly elevated in participants diagnosed with
      CTTH relative to healthy controls, while IL-18 levels were found to be
      significantly elevated in men with CTTH. Because the levels of these immune
      mediators were increased in the apparent absence of injury or infection, the
      authors sought to determine whether genetic changes were responsible for
      fluctuations in cytokine levels. Polymerase chain reaction and restriction
      fragment length polymorphism analyses were used to determine individual genotypes
      at key single nucleotide polymorphism positions in the IL-1B gene. No association
      was observed between CTTH and single nucleotide polymorphisms in the IL-1beta
      gene. CONCLUSIONS: These findings suggest that increases in key proinflammatory
      cytokine levels are associated with CTTH and the pathology of the disorder
      involves sterile neurovascular inflammation.

PMID- 23957022
TI  - Have family physicians abandoned acute care?

PMID- 23957021
TI  - Development and mixed-methods evaluation of a pain assessment video training
      program for long-term care staff.
AB  - INTRODUCTION: Inadequacies in pain assessment and management in long-term care
      have been well documented. Insufficient pain education and inaccurate beliefs
      about the nature of pain and aging have been identified as possible contributors.
      The present study addresses the need for improved, efficient and feasible
      continuing pain education through the use of an assessment training video.
      METHODS: A total of 148 long-term care staff viewed and evaluated the training
      video. Knowledge changes and pain beliefs were assessed postvideo and at a four
      week follow-up. Beliefs about pain, as well as pain and aging, were also examined
      using multivariate procedures to determine whether these variables influenced
      participants' evaluation of the video. Focus groups were also conducted, and
      transcripts were analyzed using thematic content analysis. RESULTS: Pain
      assessment knowledge improved postvideo and at the four-week follow-up.
      Participants positively evaluated the content and quality of the video.
      Individuals who held stronger beliefs (at baseline) about the organic nature of
      pain provided more positive evaluations. Barriers to implementation of practices
      in the video identified by the focus groups (and qualitative analysis) included
      time, workload and resistance to change. Facilitators to implementation included
      continued management support and observing the benefits to implementation.
      DISCUSSION: The present study provides support for the use of video training.
      However, based on the focus group results, top-down implementation approaches
      with ongoing management involvement throughout the implementation process may be
      needed to achieve sustained changes in pain assessment practices. A model useful
      for sustained implementation was proposed and discussed, and is hoped to
      facilitate future research.

PMID- 23957023
TI  - EMRs: tyranny vs triumph.

PMID- 23957024
TI  - A supplement for heart failure?

PMID- 23957025
TI  - Our success with a single-visit smoking cessation intervention.

PMID- 23957026
TI  - Targeting diabetes: the benefits of an integrative approach.

PMID- 23957027
TI  - A differential guide to 5 common eye complaints.

PMID- 23957028
TI  - Travelers' diarrhea: prevention, treatment, and post-trip evaluation.

PMID- 23957029
TI  - How apps are changing family medicine.
AB  - Medical applications for smartphones and tablets are so ubiquitous that it's easy
      to become a victim of app overload. Here's a look at FDA-approved apps, reference
      apps, and apps that FPs are "prescribing."

PMID- 23957030
TI  - Vitamin D: when it helps, when it harms.

PMID- 23957031
TI  - PURLs: corticosteroids for a sore throat?

PMID- 23957032
TI  - Erythematous plaque with yellowish papules on the shin.

PMID- 23957033
TI  - Clinical inquiry: how best to treat agitation in patients with irreversible
      dementia?

PMID- 23957034
TI  - Should you clear a child with a URI for surgery?

PMID- 23957035
TI  - Clinical utility of low-density lipoprotein particles and apolipoprotein B in
      patients with cardiovascular risk.

PMID- 23957036
TI  - What is your occlusion style?

PMID- 23957037
TI  - Full-mouth adhesive rehabilitation in case of severe dental erosion, a minimally
      invasive approach following the 3-step technique.
AB  - A full-mouth adhesive rehabilitation in case of severe dental erosion may present
      a challenge for both the clinician and the laboratory technician, not only for
      the multiple teeth to be restored, but also for their time schedule, difficult to
      be included in a busy agenda of a private practice. Thanks to the simplicity of
      the 3-step technique, full-mouth rehabilitations become easier to handle. In this
      article the treatment of a very compromised case of dental erosion (ACE class V)
      is illustrated, implementing only adhesive techniques. The very pleasing clinical
      outcome was the result of the esthetic, mechanic and most of all biological
      success achieved, confirming that minimally invasive dentistry should always be
      the driving motor of any rehabilitation, especially in patients who have already
      suffered from conspicuous tooth destruction. 

PMID- 23957038
TI  - The case for moderate "guided prep" indirect porcelain veneers in the anterior
      dentition. The pendulum of porcelain veneer preparations: from almost no-prep to
      over-prep to no-prep.
AB  - In a historical pendulum of porcelain veneer preparation concepts, an
      oversimplified version of the so-called "no prep" approaches has resurfaced. A
      case from the USC student clinics is presented, which could be easily considered
      by many as a "no prep" veneer case. Moderate tooth preparations guided by natural
      morphology were used instead with a great benefit on the final outcome. While it
      is widely accepted that minimally invasive restorative approaches should be
      favored, a certain controversy exists regarding strictly noninvasive approaches.
      The purpose of this article is to re-emphasize the concept of guided tooth
      preparations, based of natural tooth morphology (given by a wax-up and a mock
      up), a customized and sensible approach to indirect ceramic veneer tooth
      preparations. 

PMID- 23957039
TI  - Laterally moved, coronally advanced flap for the treatment of a single Stillman's
      cleft. A 5-year follow-up.
AB  - BACKGROUND: The treatment of gingival recessions is one of the important branches
      of periodontics related to esthetics. However, no surgical technique has been
      reported for the treatment of a particular type of gingival recession called
      Stillman's cleft. METHODS: The technique proposed is a laterally moved, coronally
      advanced flap. After local anesthesia, two parallel incisions, one along the
      cleft and the second parallel to the first one, have been placed beyond the
      mucogingival junction, allowing a rotating partial-thickness flap to cover the
      recession. RESULTS: The procedure, in this case presentation, resulted in
      successfully covering the previously exposed root surface. CONCLUSION: Root
      coverage of a Stillman's cleft can be obtained and maintained for 5 years follow
      up with a laterally moved, coronally advanced flap.

PMID- 23957040
TI  - Creation of the final abutment before surgery in immediate tooth replacement: two
      different approaches to obtain a customized zirconia abutment.
AB  - Specialist literature shows that the repeated disconnection of the transmucosal
      components can generate tissue recession due to the alteration of the delicate
      environment created between the abutment and surrounding soft tissue. This
      article will analyze two different techniques of creating the final abutment in
      the pre-surgery phase, evaluating 2 failing central incisors considered suitable
      for the immediate tooth replacement technique. 

PMID- 23957041
TI  - The use of indirect composite veneers to rehabilitate patients with dental
      erosion: a case report.
AB  - The evolution of restorative dental materials has led to the development of more
      direct or indirect conservative techniques to solve both functional and esthetic
      problems in anterior and posterior teeth. Several authors have concluded that
      indirect restorations are the technique of choice in complex cases where shape
      and colour are difficult to achieve and function has to be restored. Even though
      there is no clinical evidence of the appropriateness of indirect composites in
      these treatments, the latest generation of composites used indirectly in the
      anterior teeth exhibits some interesting characteristics: it supports mechanical
      stress adequately, has an excellent esthetic result and can be repaired
      intraorally. 

PMID- 23957042
TI  - Immediate Dentoalveolar Restoration of compromised sockets: a novel technique.
AB  - PURPOSE: The aim of this paper is to describe a protocol for a one-stage
      technique called Immediate Dentoalveolar Restoration (IDR), which uses autogenous
      bone grafts to restore peri-implant bone defects, presenting the results of mid
      term follow-up. SUMMARY: The patient presented a left central incisor that was
      compromised and with a total loss of buccal bone wall. The proposed treatment
      followed a protocol of immediate implantation, with a flapless surgery, using
      corticocancellous bone graft harvested from the maxillary tuberosity to restore
      the bone defect in question. The graft was shaped to the defect size and inserted
      between the implant and the remaining buccal soft tissue. The provisional
      restoration was made at the same time. The patient was followed for 36 months.
      The results were analyzed by means of clinical assessment, photography,
      periapical radiography and cone beam computed tomography. CONCLUSION: The
      treatment described appears to afford satisfactory esthetic results, with lower
      overall costs and treatment time.

PMID- 23957043
TI  - Assessment of lip position preferences in a Saudi population using computer
      imaging.
AB  - This study aimed to evaluate the perception of lip position preferences in a
      Saudi population and compare it to the perception of other populations. Master
      pictures of a male and female Saudi model were prepared with the upper lip 3 mm
      from Ricketts' E-line and the lower lip 1 mm behind. The lip position was then
      altered using computer imaging to create a range of pictures from the upper lip
      15 mm behind the E-line to the upper lip 6 mm beyond the E-line. One hundred and
      fifty-six individuals (60 male, 96 female) were asked to rate the pictures in
      terms of acceptability and also which picture they liked best. The preferences
      were compared based on gender, perception of their own lateral profile and
      history of previous orthodontic treatment. The study found that regardless of
      gender, the Saudi population has a distinct preference for lip positions that are
      further away from the E-line than the current Western standard. The population
      studied also showed a greater tolerance for deviation in the lip position away
      from the E-line than deviations towards the E-line. 

PMID- 23957044
TI  - Microabrasion using 18% hydrochloric acid and 37% phosphoric acid in various
      degrees of fluorosis - an in vivo comparision.
AB  - AIMS AND OBJECTIVES: The aim of this study was to assess the efficacy of 18%
      hydrochloric acid and 37% phosphoric acid by an in vivo comparison. METHODS:
      Sixty fluorotic permanent maxillary central incisors from 30 patients were
      divided into 3 categories. The teeth received 5 seconds (mild fluorosis), 20
      seconds (moderate fluorosis) and 30 seconds (severe fluorosis) application of 18%
      hydrochloric acid on 11 and 37% phosphoric acid on 21. Standardized intraoral
      photographies were taken immediately before, after, and one month after
      treatment. Vinyl polysiloxane impression of the patient were made before and
      after the treatment. A scanning electron microscopic (SEM) evaluation was carried
      out on the models to judge the surface alterations. Wilcoxon and Mann-Whitney
      tests were used to verify the hypothesis. RESULTS: A statistically significant
      result was obtained in the reduction of white spot opacities, intensity of stains
      and the total area occupied by the stains in mild and moderate fluorosis teeth.
      Results of severe fluorosis had an unpredictable outcome. An SEM evaluation
      revealed good improvement in the surface texture of mild and moderate fluorosis
      teeth. Teeth with severe fluorosis showed only a slight improvement. CONCLUSION:
      A microabrasion procedure is effective for treating mild and moderate fluorosis
      cases.

PMID- 23957045
TI  - Caries risk assessment in preschool children in Saudi Arabia.
AB  - PURPOSE: Caries is a prevalent condition in Saudi Arabia. At present, knowledge
      regarding caries risk factors in Saudi Arabia is limited. The present study aimed
      to identify characteristic features of Saudi preschoolers at high risk for
      caries, using the American Academy of Pediatric Dentistry caries risk assessment
      tool (CAT ) and to report the most significant caries risk predictors. MATERIALS
      AND METHODS: A sample of 407 children aged 4 and 5 years was selected randomly
      from private and public nursery schools. Their parents answered a questionnaire
      prepared using the CAT . Each child was examined for the presence of caries and
      his/her oral hygiene status. RESULTS: According to the CAT , almost all children
      (89%) were considered to be at high risk. Caries was significantly more prevalent
      among children attending public than private schools. All CAT variables were
      significantly related to the presence of caries except general health condition
      and water fluoridation. Logistic regression analysis showed previous caries
      experience, enamel demineralisation, and socio-economic status to be the most
      significant caries risk factors. CONCLUSION: Most of the Saudi children are
      considered to be at high risk for caries. Previous caries experience, enamel
      demineralisation and socioeconomic status are the most significant caries risk
      predictors. These groups should be targeted for inclusion in caries prevention
      programmes.

PMID- 23957046
TI  - A cohort study of caries incidence and baseline socioeconomic, clinical and
      demographic variables: a Kaplan-Meier survival analysis.
AB  - PURPOSE: To determine the incidence of dental caries and evaluate the influence
      of socioeconomic, clinical and demographic variables on the time for disease to
      appear in the permanent teeth after 3 years of follow-up. MATERIALS AND METHODS:
      The random sample of this cohort study consisted of 427 5-year-old preschool
      children attending 22 public preschools in Piracicaba, SP, Brazil. Dental caries
      was measured using the dmf/DMF indices. The Kaplan- Meier survival analysis
      method was used to study the isolated effect of socioeconomic, clinical and
      demographic variables on caries incidence after 3 years. A Cox proportional
      hazards regression model was built to test the influence of the variables
      collected at baseline on time to develop DMFT increment. RESULTS: Survival
      analysis showed that children without past caries experience in primary teeth at
      baseline remained caries free in permanent teeth for a longer period than
      children with past caries experience at baseline. The variables monthly family
      income, parents' educational level, number of people living in the household,
      home ownership and car ownership were not significant. CONCLUSION: Children who
      presented past caries experience in primary teeth at baseline are at greater risk
      of developing DMFT increment than children who have no past caries experience at
      baseline.

PMID- 23957047
TI  - KAP assessment of oral health and adverse pregnancy outcomes among pregnant women
      in Hyderabad, India.
AB  - PURPOSE: To conduct a questionnaire-based survey of pregnant women with
      particular reference to their knowledge, attitudes and practices in relation to
      oral care and adverse pregnancy outcomes and also to identify the various risk
      indicators for gingival bleeding during pregnancy. MATERIALS AND METHODS: This
      was a cross-sectional questionnaire-based survey using interviewer-administered,
      structured questionnaires at three maternity care centres. The study group
      comprised 359 pregnant women who were assessed for their knowledge, attitudes and
      practices regarding oral health care during pregnancy and adverse pregnancy
      outcomes. RESULTS: There were deficits in various areas of the knowledge,
      attitudes and practices of the pregnant women. The majority (87.2%) were not
      aware of the importance of oral hygiene and its probable association with adverse
      pregnancy outcomes. None of the respondents ever used dental floss and only a few
      (1.4%) had heard about it. Risk indicators that were identified in our study for
      gingival bleeding during pregnancy were: poor knowledge regarding various
      parameters, brushing only once daily and infrequent visits to the dentist.
      CONCLUSIONS: Most pregnant women need more information about oral health and
      disease prevention. It would be prudent to compile and consider their knowledge,
      attitudes and practices along with sociocultural characteristics, so that health
      education programmes are customised to different sectors of the population.

PMID- 23957048
TI  - Association between oral and general hygiene behaviours among Iranian
      adolescents.
AB  - PURPOSE: To assess the association between oral and general hygiene behaviours in
      12-year-old Iranians and the impact of sociodemographic and educational factors
      on the association. MATERIALS AND METHODS: A representative random sample of 550
      12-year-old Iranian adolescents from two deprived tribes answered a 41-item
      questionnaire on sociodemographic background, education and oral and general
      hygiene behaviours. The association between tooth cleaning frequency and other
      study outcome variables were tested using binary logistic regression. The sex
      differences in the study outcome variables were investigated using chi-square and
      Mann-Whitney tests. RESULTS: The frequency of tooth cleaning was significantly
      associated with a general hygiene behaviour: frequency of taking a bath (OR 0.5;
      95% CI: 0.3, 0.7). This association remained significant when sociodemographic
      factors and educational factors were added to the model both separately (P <
      0.001) and together (P < 0.001). Girls were significantly more likely than boys
      to clean their teeth once or more times a day (OR 2.4; 95% CI: 1.7, 3.4).
      CONCLUSION: Oral and a general hygiene behaviour were strongly associated. Oral,
      general and environmental hygiene programmes should use integrated approaches.

PMID- 23957049
TI  - Aciduric bacterial communities at three levels in dentin caries.
AB  - PURPOSE: Dentin caries constitute a complex ecosystem with a diverse microbiota
      adapted to fluctuations in nutrient concentration and acidity. However, knowledge
      about the acid tolerant microbiota at different levels in the lesion is rather
      poor. Hence, the purpose of this study was to investigate the acid tolerant
      microflora at different levels in established dentin caries lesions using solid
      pH-selective media. MATERIALS AND METHODS: Primary dentin caries lesions were
      sampled with a bur at three levels (superficial, centre and the clinically caries
      free floor of the lesion) in 10 patients. Samples were incubated on pH-neutral
      and pH-selective (pH 4.0, 4.5, 5.0, 5.5) agars. Numbers of colony-forming units
      (cfu) were determined and colonies were subsequently characterised
      morphologically and isolated. RESULTS: The total number of bacteria in the
      carious lesions, recovered using blood agar (BA), ranged from 5.88 x 103 to 5.85
      x 105 (median 2.64 x 105; range 5.80 x 105) and numbers of recovered bacteria
      decreased with decreasing agar pH. Fewer bacteria were found in the clinically
      caries-free dentin (P = 0.042), but the mean number of cfu (BA) was still 5.88 x
      103 in those samples. CONCLUSION: Each of the 10 investigated dentin caries
      lesions harboured a unique microbial flora, indicating that various combinations
      of aciduric bacteria can colonise, survive in and probably propagate dentin
      caries. Solid pH-selective agars can be used successfully to select acid-tolerant
      microorganisms in dentin caries lesions. This could be used to describe this
      subset of the total microbiome from a phenotypic point of view, an objective that
      cannot be accomplished using molecular methods.

PMID- 23957050
TI  - Identification of medically compromised dental patients in a Portuguese
      population.
AB  - PURPOSE: The age of the patients, the presence of one or more chronic disorders
      and the patients' drug regimens can influence dental treatment and oral health.
      This is a prospective, descriptive study to identify subjects with compromised
      health who received dental treatment between November 2010 and June 2011 at
      private dental practices run by graduates of the Portuguese Catholic University.
      MATERIALS AND METHODS: Application software in Microsoft Excel was developed
      containing the questionnaire, based on the EMRRH (European medical risk related
      history), which allowed the collection of data from 1603 adult patients.
      Microsoft Excel, G*Power and SPSS V.18 were used for statistical treatment.
      RESULTS: The five most frequent medical conditions found were: 1) hypertension,
      21.0%; 2) arrhythmias, 11.2%; 3) Angina pectoris, 8.3%; 4) allergies, 77%; 5)
      thyroid disease, 6.2%. The medications taken related to these were: a)
      antihypertensives, 11.0%; b) antidepressants, anxiolytics and hypnotics, 10.6%;
      c) acetylsalicylic acid, 4.2%; d) antiarrhythmic and sympathomimetic drugs, 4.1%;
      e) haemostatic treatment, 3.6%. 42.7% of the patients had no medical risks, 32.9%
      were classified as ASA II, 11.7% as ASA III and 12.7% as ASA IV. CONCLUSION: This
      study emphasises the importance of often-neglected anamnesis in oral care. The
      high prevalence of patients with medical conditions should be continuously
      studied to verify the changes over time and should be expanded to other regions
      and countries.

PMID- 23957051
TI  - FTIR microspectroscopy for rapid screening and monitoring of polyunsaturated
      fatty acid production in commercially valuable marine yeasts and protists.
AB  - The increase in polyunsaturated fatty acid (PUFA) consumption has prompted
      research into alternative resources other than fish oil. In this study, a new
      approach based on focal-plane-array Fourier transform infrared (FPA-FTIR)
      microspectroscopy and multivariate data analysis was developed for the
      characterisation of some marine microorganisms. Cell and lipid compositions in
      lipid-rich marine yeasts collected from the Australian coast were characterised
      in comparison to a commercially available PUFA-producing marine fungoid protist,
      thraustochytrid. Multivariate classification methods provided good discriminative
      accuracy evidenced from (i) separation of the yeasts from thraustochytrids and
      distinct spectral clusters among the yeasts that conformed well to their
      biological identities, and (ii) correct classification of yeasts from a totally
      independent set using cross-validation testing. The findings further indicated
      additional capability of the developed FPA-FTIR methodology, when combined with
      partial least squares regression (PLSR) analysis, for rapid monitoring of lipid
      production in one of the yeasts during the growth period, which was achieved at a
      high accuracy compared to the results obtained from the traditional lipid
      analysis based on gas chromatography. The developed FTIR-based approach when
      coupled to programmable withdrawal devices and a cytocentrifugation module would
      have strong potential as a novel online monitoring technology suited for
      bioprocessing applications and large-scale production. 

PMID- 23957052
TI  - SR-FTIR imaging of the altered cadmium sulfide yellow paints in Henri Matisse's
      Le Bonheur de vivre (1905-6)--examination of visually distinct degradation
      regions.
AB  - SR-FTIR imaging has been used to map the mid-IR active photo-degradation phases
      in two thin sections of cadmium yellow paint removed from Henri Matisse's Le
      Bonheur de vivre (1905-1906, The Barnes Foundation). These samples represent both
      the darkened cadmium yellow foliage in the upper left of the work and the
      lightened cadmium yellow field beneath the central reclining figures. The altered
      cadmium yellow paints from both regions were found to contain cadmium carbonate
      (CdCO3), cadmium sulphate (CdSO4), and cadmium oxalate (CdC2O4). Each of these
      phases was imaged to determine their positions as a function of depth, with the
      aim of better understanding the role of each phase in the degradation mechanism.
      This speciation mapping is critical because cadmium oxalate was used in this
      period as an additive in cadmium yellow light. In addition, cadmium carbonate and
      cadmium sulphate were synthesis starting materials for cadmium yellow, and so
      their distribution throughout the paint layer can provide an indication of their
      roles. It was established that cadmium oxalate is localized at the surface of the
      paint layer, cadmium carbonate is found deeper in the layer but still enriched at
      the surface, and cadmium sulphate is distributed throughout the layer. This
      distribution, along with the chloride content of the paint suggesting a cadmium
      chloride starting material, is consistent with an alteration mechanism in which
      the cadmium sulphide is oxidized to sulphate and this is then converted to
      carbonate and oxalate. The relative solubilities of the three photo-degradation
      products are also relevant to their locations in the paint film. 

PMID- 23957054
TI  - Current world literature. Anaphylaxis and insect allergy.

PMID- 23957053
TI  - Author's reply: To PMID 23159593.

PMID- 23957055
TI  - Current world literature. Pharmacotherapy and evidence based medicine.

PMID- 23957056
TI  - Reply to Screen and Simmonds: From means to mechanisms.

PMID- 23957057
TI  - Reply to Shen et al. No evidence to show nongrowing season NDVI affects spring
      phenology trend in the Tibetan Plateau over the last decade.

PMID- 23957058
TI  - Engendering ergo and safety mindsets.

PMID- 23957059
TI  - [Central nervous system tumor and glioma].

PMID- 23957060
TI  - [I. Convection-enhanced delivery for treatment of glioma].

PMID- 23957061
TI  - [II. Current status of BCNU stent in the brain for treatment of glioma].

PMID- 23957063
TI  - [IV. Epigenetic analysis for stem cell of brain cancer and treatment].

PMID- 23957062
TI  - [III. Molecular targeting therapy for glioma-bevacizumab and cilengitide].

PMID- 23957064
TI  - [Hematologic malignancies/pediatric malignancy].

PMID- 23957065
TI  - [I. Proteasome inhibitor for treatment of multiple myeloma].

PMID- 23957066
TI  - [II. Immunomodulation for multiple myeloma].

PMID- 23957067
TI  - [III. Induction chemotherapy for multiple myeloma].

PMID- 23957068
TI  - [IV. Drug discovery for bone marrow transplantation in multiple myeloma].

PMID- 23957069
TI  - Incidence of malignancies in biopsy-proven inflammatory myopathy: comment and
      erratum. Author reply.

PMID- 23957070
TI  - Graham Lancelot Hill.

PMID- 23957071
TI  - New chapters for Alpha Omega Alpha.

PMID- 23957072
TI  - The crown of a good name. W. Barry Wood, Jr., and Daniel Nathans.

PMID- 23957073
TI  - The God particle, personalized medicine, and the tragedy of the commons.

PMID- 23957074
TI  - Reverberation.

PMID- 23957075
TI  - Improving surgery: the surgery morbidity and mortality conference.

PMID- 23957076
TI  - Daily devotion.

PMID- 23957077
TI  - 2013 Edward D. Harris Professionalism Award.

PMID- 23957078
TI  - [The general internist--an endangered species?].
AB  - The status of general internal medicine is in a state of decay, and along with
      it, the position of general internists is declining. Nowadays, most internists
      depart from general internal medicine to the sub-specialties. The expected future
      shortage of general internists threatens the medical profession, endangers the
      future care of hospitalized medical patients and calls for a change in policy.

PMID- 23957079
TI  - [Rare infection--prolonged A. naeslundii bacteremia caused by severe caries].
AB  - Actinomyces is an anaerobic, gram positive, rod shape bacteria that doesn't
      create spores. Actinomyces is part of the mouth, intestines, vagina and upper
      respiratory system flora. The infection appears mostly on the face, neck, abdomen
      and pelvis in cases of mucosa injury and most common in immunosuppressed
      patients. The spread of Actinomyces through the blood system is rare. In this
      article we present a 9 year old male patient with no history of diseases who was
      diagnosed with prolonged bacteremia of A. naeslundii without specific infection
      excluding severe caries. Characterization of bacteria from the blood culture was
      performed by molecular biology and the patient was treated with Ampicillin and
      tooth extraction that led to the disappearance of the bacteremia.

PMID- 23957081
TI  - [Mediterranean diet in cancer patients and cancer free adult Arabs in Israel--a
      case-control study].
AB  - BACKGROUND: Although several studies have investigated the association of the
      Mediterranean diet (MD) with overall risk of specific cancers, data on overall
      cancer risk are sparse, especially in Arab populations. OBJECTIVES: To compare
      between the score of MD in cancer patients and cancer-free adult Israeli Arabs in
      order to identify risk factors amenable to intervention. METHODS: A case control
      study was conducted in northern Israel, involving 200 Arab subscribers of a
      regional Health Maintenance Organization (HMO). RESULTS: An inverse association
      was found (p = 0.000) between Mediterranean diet score and cancer, with OR = 0.4,
      95% CI = 0.260-0.612. CONCLUSIONS: Greater adherence to Mediterranean diet is
      associated with lower prevalence of cancer. The adoption of this dietary pattern
      also seems to moderate the prevalence of obesity and risks of chronic diseases.

PMID- 23957080
TI  - [Tuberculosis in pregnancy and puerperium].
AB  - According to the World HeaLth Organization, tuberculosis (TB) is the third
      leading cause of death worldwide among women at child bearing age. However, in
      Israel, a low TB prevalence country, TB in pregnant women is infrequent and
      infectious pulmonary TB at puerperium is rare. Early diagnosis of TB in pregnancy
      is challenging because the non-specific symptoms of early TB such as weakness,
      excess perspiration and tachycardia will usually be attributed to pregnancy.
      Furthermore, since health care givers attempt to avoid superfluous exposure of
      the fetus to radiation, and pregnant women are reluctant to be X-rayed, the
      diagnosis of active TB may be further delayed, especially if the woman is not in
      a risk group for TB. However, delaying treatment of TB in a pregnant woman,
      especially in advanced pregnancy may lead to TB in the fetus, TB infection of the
      new born transmitted from the mother who may also infect other mothers and their
      infants in the maternity ward. We report a case of highly infectious active TB
      diagnosed in a pregnant woman one week before delivery. The woman, a native
      Israeli, had no risk factor for TB except her recent stay in a high burden TB
      country. We present the diagnostic workup and therapeutic approach to the
      pregnant patient, the newborn infant and the measures applied to control
      infection. Awareness of risk factors for TB, the elusive symptoms of the disease
      during pregnancy, and implementing the necessary diagnostic workup at delivery is
      vital to minimize pregnancy related TB morbidity.

PMID- 23957082
TI  - [Exercise induced vasculitis].
AB  - Exercise induced vasculitis (or purpura) is usually misdiagnosed and ignored in
      the literature, although it is not uncommon. We report two female patients who
      developed a rash on the lower legs after walking all day long. The rash was red,
      itchy with a burning sensation. The lesions resolved after a few days with and
      without steroid treatment. Allergic etiology was suspected, therefore they were
      sent to the allergy clinic for evaluation. Exercise-induced vasculitis tends to
      occur in healthy people, especially in hot weather. Extensive investigation with
      blood or allergy tests is not needed.

PMID- 23957083
TI  - [Severe and uncommon complications of anticholinesterase intoxication in
      children].
AB  - BACKGROUND: The Northern region of the Negev desert is an endemic area of
      organophosphate and carbamate intoxications in Bedouin children. Most victims are
      intoxicated by drinking the poisonous material kept by the parents in soft drink
      bottles. Signs and symptoms of intoxication are commonly known and generally
      include various effects on the central nervous system, usually a decreased level
      of consciousness in children, cholinergic muscarinic (sweating, rhinorrhea,
      miosis, vomiting) and nicotinic (weakness) effects. Specific therapy includes
      Atropine Sulphate and Oximes. PURPOSE AND RESULTS: To describe the course of
      disease of four (out of 47) children admitted to the Division of Pediatrics with
      organophosphate or carbamate poisoning during a two-year period. The four
      children 3-17 years of age ingested the poisonous material: organophosphate
      chlorpyrifos (2 children); carbamate methomyl (one child) and an unidentified
      compound in another child. Three of the four patients ingested the poison in a
      suicide attempt. All 4 children suffered from severe and uncommon complications,
      including severe respiratory failure from different etiologies. In addition, two
      of the four suffered from a neurological deficit causing prolonged disability.
      Three had renal failure necessitating hemofiltration in one case. One child had
      severe hemodynamic failure and arrhythmias necessitating, among other therapy,
      the insertion of a temporary pace maker. Two children had (laboratory)
      pancreatitis. One of the children with severe respiratory failure died after 38
      days of extracorporeal membrane oxygenation. CONCLUSIONS: Intoxications by
      anticholinesterase compounds are not uncommon among Bedouin children in the
      Negev. This public health threat should be prevented and completely eradicated by
      the health authorities. Severe intoxication, especially in cases arising after
      suicide attempts, wherein the amount of the poisonous material is large, may be
      complicated by life threatening, multi-organ failure during and after the initial
      phase of poisoning and may progress into prolonged disability and death.

PMID- 23957084
TI  - [Cholinesterase inhibitor poisoning: a complicated medical challenge].
AB  - Exposure to insecticides, mainly cholinesterase inhibitors, is a global problem
      with substantial morbidity and mortality. Risk of intoxication is increased in
      rural areas where there is high availability and proximity of insecticides to
      families and children. Neglected storage and inadequate practice lead to
      dangerous exposure. Strict regulations and appropriate safety measures are needed
      for the prevention of exposure to insecticides. Broad toxicological knowledge is
      necessary in order to treat organophosphate and carbamate poisoned patients.
      Diagnosis is not trivial, since the identity of the poison is not always
      apparent. Multiple exposures including organic solvents are possible. The
      clinical presenting can be confusing. Measurement of cholinesterase activity is
      mandatory in establishing the diagnosis. Prompt treatment with proper antidotes
      and respiratory support is indicated. Early administration of anticonvulsants may
      mitigate central neurologic complications. Monitoring neurologic and cardiac
      function is advised for rapid identification of complications and prognosis
      evaluation. Meticulous preparedness of health care providers for insecticide
      poisoning is needed from the pre-hospital phase to emergency departments and the
      different hospital wards.

PMID- 23957085
TI  - [The social and medicolegal aspects of maternal request or non-medically
      indicated cesarean section].
AB  - Patient choice cesarean or cesarean by maternal request/ demand is a
      controversial issue. The medical literature contains evidence based data on the
      medical aspects of patient choice cesarean, risks and benefits to the mother and
      her newborn. Fewer studies focused on the social and legal aspects of patient
      choice cesarean. This opinion paper discusses the social and legal aspects of
      patient choice cesarean.

PMID- 23957086
TI  - [Combining herbs with medication--risks vs. chances].
AB  - Traditional herbal medicine is driven by the use of plants or parts of plants,
      which have undergone minimal processing in order to treat disease and improve
      health. The article: "Traditional Immunosuppression--Lei Gong Teng in Modern
      Medicine", published in this issue of "Harefuah", raises the importance of
      integrating herbal medicine within the existing medical system. However, there
      are various limitations on integrating herbology in official frameworks, such as
      bureaucratic and legislative restrictions concerning the safety and efficacy of
      the herbs. This allows the marketing of many plants without a prescription
      requirement or professional advice. Another limitation relates to therapists,
      some of whom have not undergone proper training and may recommend the improper
      use of plants, resulting in a problematic combination with drugs in some cases.
      Regulation is necessary in order to better serve both the public and doctors.
      Regulation will define who is allowed to work with herbs and this will create a
      secure integration of herbs into the formal medical world.

PMID- 23957087
TI  - [Traditional immunosuppression--Lei Gong Teng in modern medicine].
AB  - Although the origin of many common modern medicines that are routinely being used
      nowadays in healthcare is in medicinal plants and fungi, herbal medicine as a
      standalone profession is no longer included in the curricula of most Western
      medical schools. The medicinal plant Lei Gong Teng [also known as Thunder God
      Vine, Tripterygium Wilfordii Hook f., that is core to traditional Chinese herbal
      medicine, was praised for its possible anti-inflammatory properties in ancient
      traditional scripts that date back thousands of years. Yet, modern interest in
      its proven immune-modulatory properties serves as a vivid example to the bridge
      that is being built, gradually but constantly, between the tradition of healing
      arts and the world of modern therapeutics. In this review we summarize the main
      findings from an increasing number of clinical and laboratory studies published
      in top peer-reviewed medical journals that verify the traditional indications for
      which Lei Gong Teng was used medicinally. Based on these findings, and the risk
      benefit profile of the plant's debarked root, we conclude that Lei Gong Teng and
      its active metabolites should be included in the Israeli herbal pharmacopeia.

PMID- 23957088
TI  - [Smoking cessation amongst patients with mental disorders].
AB  - Cigarette smoking is very prevalent amongst patients suffering from mental
      disorders. In recent years additional scientific proof has been gathered
      regarding nicotine addiction mechanisms as effective treatments for smoking
      cessation. Some of these therapies are included in the "Basket of Health
      Services" of the State of Israel. Despite high smoking prevalence, the success
      rate for smoking cessation is low amongst patients with mental disorders. In this
      paper the possible reasons for this phenomenon are presented, as well as the
      possible biological and behavioral models that support this severe addiction
      amongst these patients. Scientifically based methods for smoking cessation are
      reviewed, including pharmacological and behavioral treatments. In addition,
      unique updated recommendations for smoking cessation amongst patients with mental
      disorders are presented.

PMID- 23957089
TI  - [The pioneer otolaryngologists in Eretz-Israel: 1911-1948].
AB  - Until 1911 there was no ear nose and throat (ENT) specialist in Eretz-Israel. Dr.
      Moshe Sherman, an ENT specialist, disembarked at the port of Jaffa on August 4,
      1911. He had trained in Moscow, and was the first otolaryngologist in the
      country. Between 1911 and 1948, over 100 otolaryngologists arrived in Eretz
      Israel and were dispersed throughout the country from Safed and Tiberias in the
      North to Rehovot in the South. These physicians brought modern and advanced
      European medicine to Israel. Many left their imprint on the development of ENT
      medicine in the country, laying the foundations of today's otolaryngologic
      services both in clinical and academic spheres. ENT medicine, like other fields
      of medicine, evolved following the establishment of the State of Israel in 1948.
      Many departments were opened and equipped with the best modern instruments and
      technology. Department heads are the pupils of our pioneer physicians. The memory
      of these talented and dedicated physicians should be remembered and cherished by
      their successors and all physicians in Israel.

PMID- 23957090
TI  - [Summary of the 30th Conference of the International Commission of Occupational
      Health (ICOH) Cancun, Mexico 2012].

PMID- 23957091
TI  - [How to integrate medical ethics into medical education during residency
      training?].

PMID- 23957092
TI  - The dentist and oral health.

PMID- 23957093
TI  - Epidemiology of oral squamous cell carcinoma.
AB  - The National Cancer Registry (NCR) of South Africa publishes the pathology-based
      cancer incidence in the country and is the main cancer data source. The data
      published by the NCR have been used extensively in the development of the draft
      national guidelines for cancer prevention and control as well as for cancer
      research. The list of contributing pathology laboratories is fairly inclusive.
      Data from the NCR and the University of Limpopo, Department of Oral Pathology for
      the five years 1997-2001 were combined and then filtered for sites in the oral
      and oropharyngeal region. Age-Standardised Incidence Rates (ASIR) and the
      Cumulative Lifetime Risk (LR) for males and females in the different population
      groups were determined. Comprehensive reporting of oral and oropharyngeal cancer
      incidence will influence the allocation of government resources for prevention
      and treatment of oral cancers.

PMID- 23957094
TI  - Aetiology of oral cancer.
AB  - The terms Oral cancer (OC) and oral squamous cell carcinoma (OSCC) are used
      interchangeably, as more than 95% of all OCs are OSCCs. Worldwide up to 275 000
      new cases of OC are seen every year. Most of these cases are seen in developing
      countries such as South Africa. Up to 50% of all patients living with OC will die
      within five years, and this survival rate has not improved over the last few
      decades. Tobacco and alcohol usage account for up to 75% of all OC cases. As
      these causative factors can be avoided, all oral health workers should be aware
      of the aetiology of OC so that sound preventive advice may be given to their
      patients. Infections and nutrition play a lesser but still important role in the
      aetiology of OC. This article reviews the importance of the aetiology of OC, with
      the emphasis on tobacco and alcohol.

PMID- 23957095
TI  - Leukoplakia and erythroplakia of the oral mucosa--a brief overview.
AB  - Leukoplakia and erythroplakia are the two most common potentially malignant
      disorders of the oral cavity. The prognosis and overall survival of a patient
      with oral cancer is dependent on the early detection of any lesion that might
      identify a patient with higher risk than normal or with early infiltration before
      metastatic disease. The role of the general dentist cannot be overstressed and
      the aim of this brief summary is to give the general practitioner an overview on
      the current concepts relating to these disorders. Leukoplakia and erythroplakia
      were traditionally known as two "precancerous lesions of the oral mucosa". The
      term "precancer" defines all lesions classified as such to have a "precancerous
      nature" implying that all of them will eventually become malignant. Through the
      years it became known that even clinically normal mucosa may show features of
      dysplasia and in some instances molecular aberrations of early malignant
      transformation may be found in the mucosa of a patient without any clinical
      lesions or dysplasia. The consensus view then was to introduce the term:
      "potentially malignant disorders" (PMD) reflecting the more generalised mucosal
      involvement in these patients. It remans a challenge to predict the behaviour of
      any of these lesions but early detection thereof remains the best chance any oral
      cancer patient will have for survival.

PMID- 23957096
TI  - Oral submucous fibrosis--a potentially malignant condition of growing concern.
AB  - Oral submucous fibrosis (OSF) is a premalignant condition that primarily affects
      the oral cavity. The clinical hallmark of this disease is the development of
      progressive trismus. The latter is a direct consequence of loss of the normal
      fibro-elasticity of the oral mucosa and replacement of the fibromuscular
      connective tissue by the deposition of dense collagen. This change in the oral
      mucosa is aetiologically linked to the areca nut chewing habit where the
      development of OSF results from the interaction of the mucosa with the chemical
      constituents of areca. Areca nuts are used as a masticatory substance either
      alone, in a self-prepared quid or in various commercial preparations known as
      paan masala and gutka. The habitual usage of these products is rapidly increasing
      and oral health professionals globally are likely to encounter patients with this
      disease. The potentially malignant nature of OSF is well documented and habitual
      areca nut chewing even in the absence of tobacco is an independent risk factor
      for oral cancer. Public health education against the areca nut chewing habit is
      essential to eradicate the deleterious effects of this habit on oral health.

PMID- 23957097
TI  - Clinical features of oral cancer.
AB  - Oral cancer (OC) is a major cause of global morbidity and mortality Squamous cell
      carcinoma accounts for more than 90% of oral malignancies and occurs most
      frequently in middle-aged to elderly patients who smoke and drink heavily. The
      overall outlook for patients diagnosed with oral squamous cell carcinoma (OSCC)
      remains poor, largely due to late clinical presentation. Early lesions are
      frequently undetected due to the lack of accompanying symptoms. Early
      recognition, diagnosis and treatment of OSCC significantly enhance patient
      survival and minimise the need for extensive surgery. It is thus essential that
      the oral health care worker (OHW) be familiar with the variable clinical
      manifestations of both potentially malignant disorders (PMD) as well as invasive
      malignancy. OC screening, particularly in high-risk patients should be an
      integral component of routine intra-oral clinical examination. The aim of this
      article is to highlight the varied clinical appearance of OC and to emphasise the
      importance of early recognition and diagnosis.

PMID- 23957098
TI  - Oropharyngeal carcinoma: what the dentist should know.
AB  - HPV-related oropharyngeal carcinoma (OPC) is a clinically and molecularly
      distinct form of squamous cell carcinoma (SCC) which has recently shown a dramatc
      increase in global incidence. The aetiology, clinical presentation and overall
      prognosis differ from conventional tobacco and alcohol related SCC of the oral
      cavity. OPC is seen in a subset of younger predominantly male patients.
      Acquisition of high-risk HPV subtypes is related to oral sex practices with
      multiple partners. OPC originates deep within tonsillar crypts which hinders
      early clinical detection. Patients present with advanced disease and frequent
      cervical lymph node metastases. Despite its aggressive nature, the overall
      prognosis remains excellent compared wth conventional oral SCC. The increased
      incidence of OPC is of clinical significance to the general dentist and should
      always be considered in the clinical differential diagnosis in a young, otherwise
      healthy, patient with persistent cervical lymph node enlargement. Older patients
      with a history of tobacco usage and alcohol consumption may also present with
      conventional SCC of the oropharynx. Potentially malignant disease may precede
      tumour development at this site in such cases. Clinical examination of the
      oropharynx should therefore be performed as part of routine dental consultation.

PMID- 23957099
TI  - Treatment concepts of oral cancer.
AB  - The mortality of oral cancer (OC) has shown only moderate improvement over recent
      decades. Treatment of OC remains mainly surgical with increasing contributions
      from radio- and chemotherapy. Early diagnosis and adequate management improves
      patient prognosis whilst lymphatic spread worsens the prognosis significantly.
      Copious extirpation of the tumour achieving tumour-free margins, as well as the
      effective removal of affected or suspect lymph nodes are vital steps to ensure
      long-term survival. Reconstructive ablities have improved to such an extent that
      many patients can be fully integrated in society after treatment. New modalities
      such as intensity modulated radiation therapy (IMRT) or volumetric modulated arc
      therapy (VMAT) ensures selective radiation and significantly contributes to
      improved quality of life. Photodynamic therapy and other targeted therapy options
      will play an increasingly important role in the future.

PMID- 23957100
TI  - Malignant tumours of the jaws.
AB  - Almost all variants of malignant primary and secondary tumours of bone have been
      described as occurring within the jaws. Odontogenic carcinomas and sarcomas are
      peculiar to the jawbones and are distinctly uncommon. Non-odontogenic tumours in
      comparison arise with more frequency, yet the maxilla and mandible remain unusual
      sites for most primary and secondary non-odontogenic tumours of bone. The most
      commonly occurring primary bone tumours affecting the jaws include osteosarcoma,
      Burkitt's lymphoma and multiple myeloma, while secondary or metastatic tumours to
      the jaws are rare in contrast to the remainder of the skeleton.

PMID- 23957101
TI  - Soft tissue sarcomas of the head and neck.
AB  - This is a review of the main clinical and microscopical features of the most
      common sarcomas of the soft tissues of the head and neck.

PMID- 23957102
TI  - Metastases to the oral cavity.
AB  - Metastatic spread to the oral cavity of a malignant neoplasm is a rare yet
      important sign of advanced systemic malignant disease. This manuscript briefly
      describes the metastatic process and highlights the most common neoplasms that
      metastasise to the oral cavity as well as their clinical and radiological
      presentations. The role of the patients' history in suspecting metastatic disease
      and the importance of a microscopic diagnosis is emphasised.

PMID- 23957103
TI  - HIV/AIDS associated malignancies of the head and neck.
AB  - Patients with HIV/AIDS are at increased risk for the development of malignancy.
      Kaposi's sarcoma, non-Hodgkin's lymphoma and cervical carcinoma in women are
      regarded as AIDS-defining malignancies. The spectrum of malignancy is, however,
      changing, particularly where patients receive highly active antiretroviral
      therapy (HAART). South Africa has the highest number of HIV-infected individuals
      globally. The possibility of the oral health care worker encountering HIV/AIDS
      related pathology therefore seems inevitable. The aim of this article is to
      heighten the awareness of head and neck malignancies occurring in HIV/AIDS whilst
      highlighting some of the clinical features in order to facilitate early
      recognition and diagnosis. It is of clinical significance that in many instances,
      identification of these malignancies precedes HIV/AIDS diagnosis. Optimal patient
      management requires close co-operation between the oral health care practitioner
      and the extended health care team.

PMID- 23957104
TI  - The scope of maxillofacial prosthodontics.
AB  - Oral cancer may affect up to 275 000 new patients per year worldwide. Many of
      these will be disfigured by the destruction of tissue within the face and head
      area. Maxillofacial prosthodontics can play a vital role in restoring such
      patients to a semblance of normality in appearance and function. This article
      will describe the role of maxillofacial prosthodontics in the treatment of these
      oral cancer patients.

PMID- 23957105
TI  - Dental ethics case 27. The orthodontic dilemma of non-compliance.

PMID- 23957106
TI  - Oral medicine case book 45. Periosteal osteosarcoma of the mandible.

PMID- 23957107
TI  - Introduction of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC)
      to the surgery program.
AB  - Heated Intraoperative Intraperitoneal Chemotherapy (HIPEC) offers a chance for
      extended survival, or cure, to patients facing specific types of invasive
      abdominal cancer. This article will explore the perioperative facets of
      implementing a peritoneal malignancy program that includes the HIPEC procedure.
      In exploring this procedure, experiences will be shared with the intent of
      optimizing patient care for potential surgical programs and perioperative staff.
      The examination will illustrate the respective program development areas such as
      training, budgetary requirements and patient care considerations. Further, the
      dialogue will investigate patient selection, preoperative preparation and
      intraoperative considerations. Lastly, the article will reveal the specific
      shortterm and long-term patient outcomes starting with the immediate
      postoperative phase.

PMID- 23957108
TI  - Spotlight on ORNAC members. An interview with Aline Titizian, RN, BsCN. Interview
      by Catherine Harley.

PMID- 23957109
TI  - Medical professionalism.

PMID- 23957110
TI  - Pertussis and the cocoon.

PMID- 23957111
TI  - Case report of papillary breast carcinoma, cystic.
AB  - BACKGROUND: Intracystic papillary carcinoma of the breast (ICP) is a rare form of
      noninvasive breast cancer. The average age of onset is 65 years. Patients with
      ICP have a greater than 15-year survival rate advantage compared to patients with
      other breast carcinomas. There have been no reports of disease-related deaths in
      patients with ICP and no increased risk of disease in the contralateral breast.
      No definitive conclusions have been made regarding adjuvant treatment; however,
      ICP should generally be treated like ductal carcinoma in situ (DCIS). Tamoxifen
      is often recommended.

PMID- 23957112
TI  - Pheochromocytoma - review and biochemical workup.
AB  - A commonly received question in the clinical laboratory is as follows: what is
      the best test for pheochromocytoma? A widely variable presentation and
      potentially catastrophic consequence make this a feared neoplasm despite its
      infrequent encounter. Because various biochemical testing modalities are
      available, test selection is often confusing. This selection process can be made
      easier through a better understanding of catecholamine producing neoplasms. The
      aim of this article is to provide a review of catecholamine producing neoplasms
      and give recommendations on appropriate test selection.

PMID- 23957113
TI  - Extreme multi-level anterior cervical discectomy and fusion.
AB  - The use of anterior cervical discectomy and fusion (ACDF) is a common procedure
      used to treat those who suffer from degenerative disc disease (DDD) of the
      cervical spine which may result in spondylolisthesis, spinal stenosis, disc
      herniation, nerve root and/or cord compression. ACDF is regularly used for the
      fusion of one to four cervical spine levels; however, the literature documenting
      the fusion of 5 or 6 levels is surprisingly lacking. In this retrospective review
      of our case series, we document two 5-level and two 6-level ACDF in elderly
      patients using custom made titanium fusion plates and patellar allograft bone for
      interbody placement without posterior fixation. The documentation of these long
      anterior constructs without supplemental posterior fixation or the use of a halo
      vest apparatus, but a simple neck collar for three months, is an important
      contribution to the literature illustrating that with utilization of appropriate
      technique, a high number of levels can be safely fused in the elderly patients
      necessitating this particular procedure.

PMID- 23957115
TI  - The good, the bad, and the ugly.

PMID- 23957114
TI  - Treating type 2 diabetes with canagliflozin.

PMID- 23957116
TI  - Tobacco use: A health epidemic aimed at our youth.

PMID- 23957117
TI  - Trust.

PMID- 23957118
TI  - Hospital value-based purchasing.

PMID- 23957119
TI  - Ruling jeopardizes authority of state medical boards.

PMID- 23957120
TI  - "Is the nursing role no longer valued"?

PMID- 23957121
TI  - Call to address HCA challenges.

PMID- 23957122
TI  - "Education must prepare nurses to speak out about poor care".

PMID- 23957123
TI  - "Don't make me laugh: comedy bursts the continence taboo".

PMID- 23957124
TI  - Live kidney transplant from an unrelated donor.
AB  - This article provides an insight into the experience of live donation from the
      donor and recipient perspectives from diagnosis until 18 months after
      transplantation. The lead author details the diagnosis of end-stage renal failure
      in her partner and their decision for her to donate a kidney.

PMID- 23957125
TI  - Does NHS staff wellbeing affect patients' experience of care?

PMID- 23957126
TI  - Reversing deterioration in continence services.
AB  - Despite the growing prevalence of incontinence and the recognition that it is a
      significant factor in admissions to hospitals and residential care, continence
      care is receiving less funding. This article compares the findings of a
      continence care survey undertaken in 2007 with one published in 2013. The survey
      shows there has been a reduction in numbers of specialist continence staff,
      particularly senior posts, an increased number of patients seeking help, a
      decrease in funding, fewer continence products being supplied and growing waiting
      lists.

PMID- 23957127
TI  - Maintaining continence in people with dementia.
AB  - Incontinence is not an inevitable consequence of having dementia, but continence
      can be an issue. Nurses need to have strategies in place to provide supportive
      continence care for people with dementia not only in hospitals, care homes and
      day care services, but also for those living at home alone or with a carer. For
      this to happen, the patient and home environment need to be assessed. This
      article explores steps that can be taken to preserve the dignity of people with
      dementia if they become incontinent. The role of health professionals in
      hospitals is discussed, as well as changes that can be made in patients' own
      homes.

PMID- 23957128
TI  - 60 second with Susan Stewart.

PMID- 23957129
TI  - Partnership not paternalism.

PMID- 23957130
TI  - Compassionate leaders know how others see them.

PMID- 23957131
TI  - Cost cutting hits children's services.

PMID- 23957132
TI  - Staff shortages linked to higher avoidable death rates.

PMID- 23957133
TI  - Specialist nurses reach out to young people with disabilities.

PMID- 23957134
TI  - Future of children's heart surgery services in England remains unclear.

PMID- 23957135
TI  - Emergency call.

PMID- 23957136
TI  - Helping children who require long-term parenteral nutrition.
AB  - Parenteral nutrition (PN) is a therapy that is complex and can lead to serious
      complications such as infection of the central venous catheter. A follow-up audit
      beginning in 2007 showed that, in a cohort of 36, 16 children were transferred
      from the neonatal unit and 20 had conditions that might be similar to adult
      indications for PN. The audit has underlined the fact that the use of PN should
      be carefully assessed, monitored and discontinued as soon as possible. Intestinal
      failure is the most common indication for PN and its management requires specific
      training.

PMID- 23957137
TI  - Dental caries in children: a sign of maltreatment or abuse?
AB  - Healthcare professionals are required to complete regular training in
      safeguarding children and, in this training, dental caries and poor oral hygiene
      are often cited as potential indicators of neglect. Nurses may be the first
      healthcare professionals to detect poor oral health in a child, although
      unfortunately the relationship between neglect and dental caries in children is
      unclear. Any healthcare professional suspicious of child abuse or neglect has
      responsibility to follow the appropriate protocol and report their concerns. If
      dental neglect is suspected then the opinion of a dentist will be required as
      part of the investigation.

PMID- 23957138
TI  - Daytime wetting in children and acquisition of bladder control.
AB  - Daytime wetting is a common problem in early childhood. This article explains how
      the infant's bladder develops and how children are able to develop bladder
      control. The need for more structured toilet training at an earlier age than is
      standard today is proposed to prevent children having difficulty attaining and
      maintaining bladder control, which may be associated with delays in becoming
      continent and the development of daytime wetting. The article discusses common
      daytime wetting problems and describes how they can be assessed using a
      structured, standardised approach to history taking. Management using bladder
      retraining in the form of modified urotherapy is outlined, which aims to retrain
      the bladder without the need for surgery or pharmaceutical treatment.

PMID- 23957139
TI  - A reward in itself.

PMID- 23957140
TI  - Onset of molar incisor hypomineralization (MIH).
AB  - The etiological factors and timing of the onset of molar incisor
      hypomineralization (MIH) are still not clear. The aim of this study was to
      examine ground radial and sagittal sections from teeth diagnosed with MIH using
      light microscopy, polarized light microscopy and X-ray micro-computed tomography
      (XMCT) and to estimate the onset and timing of the MIH and to relate the
      hypomineralized enamel to the incremental lines. Thirteen extracted permanent
      first molars diagnosed MIH, were analyzed with light microscopy and XMCT. The
      hypomineralized areas were mainly located in the mesio-buccal cusps, starting at
      the enamel-dentin-junction and continuing towards the enamel surface. In a
      relative gray scale analysis the values decreased from the EDJ towards the enamel
      surface. The findings indicate that the ameloblasts in the hypomineralized enamel
      are capable of forming an enamel of normal thickness, but with a substantial
      reduction of their capacity for maturation of enamel. Chronologically, it is
      estimated that the timing of the disturbance is at a period during the first 6-7
      months of age.

PMID- 23957141
TI  - Treatment with local hemostatic agents and primary closure after tooth extraction
      in warfarin treated patients.
AB  - The aim of this retrospective study was to assess the frequency of postoperative
      bleeding in patients on warfarin after tooth removal followed by a complete soft
      tissue closure of the surgical site. A total of 124 consecutive patients, 69
      males and 55 females with a mean age of 71 years (range 28-95 years) were
      included in this study. Inclusion criteria were patients on warfarin with an INR
      <or=3.5 who were referred for tooth removal (single or multiple) during 2004
      2009. After tooth extraction all sockets were packed with an absorbable
      haemostatic gelatin sponge or a collagen fleece and subsequently the sockets was
      primary closed with sutures. 5/124 (4%) patients returned with postoperative
      bleedings. All patients with a postoperative bleeding had received a surgical
      extraction in the posterior part of the maxilla. Consequently no patient had a
      postoperative bleeding in the mandible. None of the 124 patients returned to the
      clinic with a dry socket or postoperative pain. 3/124 (2%) patients returned with
      postoperative infection that required antibiotic treatment. All patients who bled
      were managed conservatively and none was admitted to hospital. CONCLUSION:
      According to the protocol of this study (local hemostatic, primary closure,
      sutures and tranexamic acid) the risk of postoperative bleeding after tooth
      removal in patients on continued warfarin medication is low.

PMID- 23957142
TI  - Comparison of diagnostic performance on approximal caries detection among Swedish
      and Chinese senior dental students using analogue and digital radiographs.
AB  - The objective was to investigate diagnostic performance on approximal caries
      detection among Swedish and Chinese dental students using analogue and digital
      radiographs in vitro. Additionally, to compare the diagnostic accuracy of two
      image modalities for approximal caries detection. 46 extracted premolars and
      molars were mounted in blocks and exposed with two intra-oral systems, one CCD
      based digital radiographs and one with conventional films. 10 Swedish and 10
      Chinese senior dental students diagnosed the approximal sites of the teeth
      exposed with the digital and analogue images. A 5 point diagnosis confidence
      scale was applied for caries registration for all the observers. Subsequently,
      the teeth were sectioned and histo-pathologically analyzed in order to obtain a
      gold standard. The data were analyzed in terms of receiver operating
      characteristic (ROC) curves for evaluation of diagnostic accuracy of the two
      radiographic methods and for the two groups of students for enamel and dentinal
      caries detection, respectively. The area under the ROC curve was significantly
      higher for dentinal caries detection compared with enamel caries detection for
      both Chinese and Swedish students and for both imaging modalities (p<0.001). The
      present results indicated that the students' ability for enamel caries detection
      on approximal surfaces was poor. Neither between the two student groups (p=0.15
      0.64) nor between the two image modalities (p=0.34-0.91) a statistically
      significant difference in detecting approximal caries was found. CONCLUSIONS: The
      two different intra-oral x-ray systems were equally accurate. Chinese and Swedish
      students showed similar outcomes in their performance for approximal caries
      detection.

PMID- 23957143
TI  - The prevalence and alterations of furcation involvements 13 to 16 years after
      periodontal treatment.
AB  - The aim of this study was to evaluate the long term outcome of furcation involved
      molars in a population treated for periodontal disease. Initially, the study
      sample was 147 referred periodontal patients. Periodontal treatment consisted of
      oral hygiene instructions, supra- and subgingival scaling and periodontal
      surgery. After treatment 99 patients participated in a two year study on root
      caries. The patients got maintenance treatment every third to fourth month during
      2 years. At the end of that study the patients were periodontally healthy and
      were referred back for supportive treatment to the referring dentist. Thirteen to
      16 years after periodontal treatment 81 patients were still alive and 64 accepted
      a re-examination. At the start of the observation period the remaining 64
      patients had in total 1537 teeth. During the 13 to 16 year follow up 217 teeth
      were lost. The number of molars at baseline was 361. The number of furcation
      involvement with different degrees were; 267 (0), 67 (I), 25 (II) and 2 (III)
      respectively. Totally 69 molars were lost during follow up. The proportion of
      molar loss according to the degree of furcation involvements 0 to III at baseline
      were 15%, 29%, 40% and 100% respectively. It was a significant greater risk of
      loosing an initially furcation involved molar than a single rooted tooth
      (p<0.0001). The risk of loosing an initially furcated molar increased with the
      degree of furcation involvement (degree I; p<0.05, degree II; p<0.01). I N
      CONCLUSION: During a long term observation period molars with furcation
      involvements are more frequently lost than not furcation involved molars.
      However, two thirds are still in function 13 to 16 years after treatment which
      indicate that molars with furcation involvements might survive long after
      periodontal treatment.

PMID- 23957144
TI  - Molar position associated with a missing opposed and/or adjacent tooth: a follow
      up study in women.
AB  - The purpose of the study was to assess (i) the degree of overeruption of molars
      lacking opposed teeth and (ii) the inclination of molars with a mesial edentulous
      space and alsoto study (iii) changes during a 12 year period. The subject sample
      originated from the prospective population study of women in Gothenburg, Sweden
      where scanned panoramic radiographs taken with an interval of 12 years were
      analysed. Tipping as well as overeruption were scored on the two images according
      to a five-level scale. Sixty-seven subjects fulfilled the inclusion criteria at
      baseline and were referred to as "the non-extraction group". Further 35 subjects
      had lost the opposed and/or the adjacent tooth/teeth during the 12-year follow-up
      period: "the extraction-group". These groups were studied separately and a
      comparison between these groups was performed. The prevalence of molars tipped
      more than 15 degrees at baseline was 17.1% in the upper jaw and 44.3 % in the
      lower jaw, in the non-extraction group. At baseline overeruption was seen in 25 %
      of the unopposed upper molars and none of lower molars in the non-extraction
      group. The prevalence of tipping and overeruption was statistical significant
      less in the extraction group (P<0.01), than in the non-extraction group at
      baseline, but at follow-up no statistical significant group differences existed.
      IN CONCLUSION: The prevalence of tipped molars facing a mesial edentulous space
      and overerupted unopposed molars increased in adults during the 12-year period
      but the changes were small. Overeruption and tipping is most pronounced
      immediately after extractions.

PMID- 23957146
TI  - [Isolation and identification of Cronobacter (Enterobacter sakazakii) strains
      from food].
AB  - OBJECTIVE: This study aimed to detect and quantify Cronobacter in 300 powdered
      milk samples and 50 non-powdered milk samples. Totally, 24 Cronobacter (formerly
      Enterobacter sakazakii) strains isolated from powdered milk and other foods were
      identified and confirmed. METHODS: Cronobacter strains were detected
      quantitatively using most probable number (MPN) method and molecular detection
      method. We identified 24 Cronobacter strains using biochemical patterns,
      including indole production and dulcitol, malonate, melezitose, turanose, and myo
      Inositol utilization. Of the 24 strains, their 16S rRNA genes were sequenced, and
      constructed phylogenetic tree by N-J (Neighbour-Joining) with the 16S rRNA gene
      sequences of 17 identified Cronobacter strains and 10 non-Cronobacter strains.
      RESULTS: Quantitative detection showed that Cronobacter strains were detected in
      23 out of 350 samples yielding 6.6% detection rate. Twenty-four Cronobacter
      strains were isolated from 23 samples and the Cronobacter was more than 100
      MPN/100g in 4 samples out of 23 samples. The 24 Cronobacter spp. isolates strains
      were identified and confirmed, including 19 Cronobacter sakazakii strains, 2 C.
      malonaticus strains, 2 C. dubliensis subsp. lactaridi strains, and 1 C.
      muytjensii strain. CONCLUSION: The combination of molecular detection method and
      most probable number (MPN) method could be suitable for the detection of
      Cronobacter in powdered milk, with low rate of contamination and high demand of
      quantitative detection. 24 isolated strains were confirmed and identified by
      biochemical patterns and molecular technology, and C. sakazakii could be the
      dominant species. The problem of Cronobacter in powdered milk should be a hidden
      danger to nurseling, and should catch the government and consumer's attention.

PMID- 23957145
TI  - [Genomic characteristics of bocavirus and molecular mechanism of its
      pathogenicity--a review].
AB  - Bocavirus was considered as a member of the subfamily parvoviriae of the family
      parvoviridae, which includes bovine bocavirus, minute virus of canines, human
      bocavirus, as well as the newly identified swine bocavirus, gorilla bocavirus,
      feline bocavirus, canine bocavirus and bocavirus identified in California sea
      lion sample. At present, as an emerging pathogen, bocavirus members attract great
      attention by researchers worldwide. We reviewed published papers in combination
      with our study for several aspects of bocavirus family including their
      classification, genome structure and replication, clinical pathogenic
      characteristics and molecular pathogenesis.

PMID- 23957147
TI  - [Activity of the SrfAC-A domain from Bacillus subtilis fmbj].
AB  - OBJECTIVE: We studied the A domain of surfactin synthase in vitro to obtain new
      surfactin analogues. METHODS: We cloned the srfAC-A gene from Bacillus subtilis
      fmbj by PCR, and constructed a recombinant expression vector named pET-23a-srfAC
      A. Furthermore, the SrfAC-A domain was expressed in E. coli BL21 (DE3) and
      purified by Ni-NTA agarose column. Then the activity of srfAC-A domain was
      detected. RESULTS: The srfAC-A domain had specificity towards Ile, but almost no
      activity to other amino acids. CONCLUSION: The independent A domain from
      surfactin synthase had selectivity to specific amino acids in vitro.

PMID- 23957148
TI  - [Use of entomopathogenic fungi to degrade wax secreted by Ceroplastes japonicus].
AB  - OBJECTIVE: We used entomopathogenic fungi to degrade insect wax. METHODS: We used
      four fungal strains, Lecanicilliurn lecanii V3. 4504, V3. 4505, Beauveria
      bassiana FDB01, and Metarhizium anisopliae TSL06. Wax coverings of female adults
      of Ceroplastes japonicus Green (Insecta: Hemiptera: Coccoidea) were used as the
      sole carbon source in the mineral medium. RESULTS: All of the 4 strains could
      grow, reproduce, produce enzymes, and degrade wax. During a 7-day culture, the
      highest lipase activities of the 4 strains, V3. 4504, V3. 4505, FDB01, and TSL06
      were 0.128 +/- 0.017, 0.056 +/- 0.002, 0.124 +/- 0.011, and 0.149 +/- 0.005 U/mL,
      respectively. The dehydrogenases activities of the 4 strains were 0.075 +/-
      0.003, 0.074 +/- 0.003, 0.061 +/- 0.04, and 0. 066 +/- 0. 002 U/mL respectively.
      The degradation rates of wax by the 4 strains were 18.20 +/- 0.019, 11.00 +/-
      0.011, 15.4 +/- 0.017, and 23.10 +/- 0.031%, respectively. CONCLUSION: The 4
      strains could depredate wax of C. japonicus.

PMID- 23957149
TI  - [Screening of chlorobenzene-degrading bacterium and purification of its
      degradation enzyme].
AB  - OBJECTIVE: We screened a bacterial strain capable of degrading chlorobenzene, and
      purified the corresponding degradation enzyme. METHODS: The strain was screened
      by gradient enrichment culture and sterile filter paper plate method, and
      identified by morphology and 16S rRNA gene sequence. Chlorobenzene concentration
      in the liquid culture was determined by gas chromatography. Degradation
      capability was assayed by the proportion of chlorobenzene degraded per cells. The
      purity quotient and molecular weight of the purified degradation enzyme were
      determined by gel per cell. electrophoresis. RESULTS: The isolated bacterium,
      LW13, used chlorobenzene in activated sludge as sole carbon and energy source.
      Cells were 2.3 microm long and 0.8 microm wide, with several terminal flagella.
      Strain LW13 was 95.5% similar to Lysinibacillus fusiformis, and its degradation
      enzyme was a positively-charged exoenzyme (molecular weight about 57 kDa). The
      optimal temperature and pH of the purified enzyme were approximately 40 degrees C
      and 8.0, respectively. CONCLUSION: Strain LW13 belongs to genus Lysinibacillus,
      and can degrade chlorobenzene (500-2000 mg/L).

PMID- 23957150
TI  - [Screening and identification of glycoproteins from Campylobacter jejuni NCTC
      11168 based on specific affinity between lectins and glycoproteins].
AB  - OBJECTIVE: To screen glycoproteins from Campylobacter jejuni NCTC 11168. METHODS:
      We introduced a screening strategy based on specific affinity between lectins and
      glycoproteins. First, the specific affinity between Soybean Agglutinin (SBA) and
      glycoproteins in C. jejuni was confirmed by western blotting. Then, magnetic
      beads coating with Soybean Agglutinin (SBA) were used to capture the putative
      glycoproteins. Putative glycoproteins were competitively eluted by N
      acetylgalactosamine and separated by two-dimensional gel electrophoresis. Spots
      in gels were further analyzed by mass spectrometry. RESULTS: A total of 22
      proteins were identified by mass spectrometric analysis, of which 5 have ever
      been identified to be glycoproteins. Others including Cj0633 have not been proved
      to be glycosylated so far. CONCLUSION: The method could be used to screen
      glycoproteins in bacteria.

PMID- 23957151
TI  - [Isolation and identification of rumen bacteria for cellulolytic enzyme
      production].
AB  - OBJECTIVE: We screened aerobic bacteria with cellulolytic activity from ruminal
      fluid of sheep, cattle and camel in Xinjiang. METHOD: Fresh ruminal fluid was
      inoculated on sterilized sodium carboxymethylcellulose agar plates. Highly
      cellulolytic aerobic bacteria were screened out by using Congo red staining and
      liquid secondary screening culture media. The combination of morphological and
      biochemical test with 16SrDNA sequence analysis were used to classify the
      strains. Enzymatic activities of four strains with strong cellulose-decomposing
      abilities were studied under different culture conditions. RESULTS: Out 84
      isolated cellulolytic strains, 40 exhibited strong abilities in decomposing
      cellulose. They are including 37 Gram-negative isolates and 3 Gram-positive
      strains. Identification of these 40 strains shows that they belong to 11 species
      of 6 genera, 16 strains in Stenotrophomonas maltophilia, 10 Ochrobactrum, 5
      Sphingobacterium, 3 Microbacterium, 3 Paracoccus and 2 Pseudomonas. The results
      of the enzymatic studies of four strains with strong cellulolytic abilities
      indicates that the strains have the best enzyme producing property when straw
      powder was chosen as the carbon source; the pH at 5.5 -6.0 and temperature at 37
      degrees C. CONCLUSION: The strains with highly cellulolytic abilities isolated
      from ruminal fluid show strong abilities in cellulose decomposition.

PMID- 23957152
TI  - [Distribution of endophytic fungi in Oxytropis glabra DC].
AB  - OBJECTIVE: Endophytic fungi were detected and isolated from the stems, leaves,
      petioles and seeds of Oxytropis glabra DC sampled from Alashan of Inner Mongolia
      to investigate the infection rate and species distribution in different tissues.
      METHODS: The endophytic fungi infection rate and distribution of species in
      different tissues were investigated by making temporary slides, staining,
      isolation and identification. RESULTS: Endophytic fungi were detected and
      observed from all parts (stems, leaves, petioles and seeds) of the plant by
      temporary slides staining. A total of 79 isolates were cultivated from 4
      different tissues by common separation methods, which belonged to 10 genera after
      identification. The infection rate and separation rate were seeds > leaves >
      stems > petioles. Undifilum oxytropis, Embellisia sp. L12 and Fusarium equiseti
      were the dominant species in this plant with the relative isolate frequency
      77.32%, 64.00% and 50.00%, respectively. CONCLUSION: Endophytic fungi were
      commonly found in the all parts of Oxytropis glabra DC. There was an obviously
      difference in quantity, species and distribution of the endophytic fungi between
      different parts of plant. Seeds and leaves were the most vulnerable to infection
      and colonization by the endophytic fungi.

PMID- 23957153
TI  - [Biological characteristics of an enteroinvasive Escherichia coli strain with
      tatABC deletion].
AB  - OBJECTIVE: To study the relationship between twin-arginine translocation system
      (Tat) system with the biological characteristics of enteroinvasive Escherichia
      coli (EIEC). METHODS: Through homologous recombination, we constructed EIEC's
      tatABC gene deletion strain and complementary strain, and explored their impact
      on bacterial form, substrate transport function as well as on HeLa cells and
      guinea pig's corneal invasion force. RESULTS: The tatABC gene deletion strain had
      apparent changes in bacterial form, loss of substrate transporter function, and
      significant weakened bacterial invasion force (the number of the deletion strain
      invading into HeLa cells was decreased significantly, and the ability of its
      corneal lesion capacity of the guinea pig was significantly weakened), while the
      complementary strain was similar to the wild strain in the above respects.
      CONCLUSION: EIEC's Tat protein transport system is closely related with the
      biological characteristics of EIEC.

PMID- 23957154
TI  - [Diagnosis of white spot syndrome virus in farm crawfish in Anhui province and
      its epidemiological source].
AB  - OBJECTIVE: The aims of this study were to find out the pathogen causing high
      mortality of the crawfish population in Anhui over the past years. To provide the
      strategy for controlling the spread of the disease, an investigation was
      conducted to trace the origin of the pathogen. METHODS: Crawfish samples were
      tested by nested PCR, to diagnose the White Spot Syndrome Virus (WSSV). Healthy
      crawfish were inoculated with the supernatant of tissue homogenates. The viral
      suspension was purified using sucrose density gradients. The gill samples
      infected with purified virus were then subject to the transmission electron
      microscopy (TEM). The possible sources, including pond water, feedstuff, crabs,
      water plants, were investigated. RESULTS: Crawfish samples and commercial feeds
      exhibited all positive for WSSV. Challenge model on healthy crawfish recovered
      similar symptoms as the naturally infected ones on 7 to 9 days after inoculation.
      The viral particles were observed under TEM. CONCLUSION: Our findings indicated
      that WSSV was the causative agent that led to high mortality in the crawfish
      population in this area. These results demonstrated that the exotic viruses are
      derived from the regions where the frozen feeds were contaminated with WSSV
      infected shell debris.

PMID- 23957155
TI  - [Combination utility of phages GH15 and K against Staphylococcus aureus].
AB  - OBJECTIVE: In the present report, we compared the biological characteristic of
      staphylococci phage GH15 and K. We also determined the therapeutic potential of
      the combination utility of two phages. METHODS: The patterns of GH15 and K were
      detected using transmission electron microscopy. We also detected the host range
      and the one-step curve of phage GH15 and K. The lytic ability of mono-phage and
      phage cocktail was compared in vitro. Finally, the treatment effect of mono-phage
      and phage cocktail aginst lethal methicillin-resistant Staphylococcus aureus
      (MRSA) infection in mice was detected. RESULTS: The length of GH15 tail was
      longer than that of K either in the state of contraction or noncontraction. GH15
      had broader host range than K whereas both possess 7 common host strains.
      Although the phage cocktail had equivalent bactericidal capacity with mono-phage
      to most common host strains, the phage cocktail manifested more effective
      protection against lethal W4661 infection in mice than any mono-phage. A single
      smaller dose injection of phage cocktail was sufficient to protect mice
      effectively from fatal infection. CONCLUSION: Our results provide strong evidence
      towards the therapeutic use of phage cocktail as an alternative to antibiotics
      for acute infection caused by multi-drug resistant Staphylococcus aureus.

PMID- 23957156
TI  - [Establishment of a porcine CD151 transgenic PK-15 cell line susceptible to
      porcine reproductive and respiratory syndrome virus].
AB  - OBJECTIVE: In order to study the role of porcine CD151 in infection of porcine
      cells by porcine reproductive and respiratory syndrome virus (PRRSV), we
      established a porcine CD151 transgenic PK-15 cell line. METHODS: The full-length
      complementary DNA (cDNA) for porcine CD151 was amplified from porcine alveolar
      macrophages by reverse transcription-polymerase chain reaction (RT-PCR), and
      subcloned into eukaryotic expression vector pcDNA3. The recombinant vector pcDNA
      CD151 was transfected into PK-15 cells and the transgenic cell line was generated
      after G418 selection. Transcription of the CD151 cDNA in transgenic cell line was
      detected by RT-PCR and immunofluorescence. The cell line, together with control
      cell lines PK-15, 3D4-CD163 and MARC-145, was infected with PRRSV, and the viral
      RNA genome or antigens in the infected cells was detected by RT-PCR or
      immunofluorescence. At different time points post-infection, the virus was
      harvested and titrated on MARC-145 cells. RESULTS: The expected size of porcine
      CD151 cDNA was amplified with a sequence identity of 99.7% to the published
      sequence. From the pcDNA-CD151-transfected cell culture, a transgenic cell line
      PK15-CD151 was generated and correct expression of porcine CD151 was confirmed.
      After PRRSV infection, the viral RNA genome and antigens were detected in the
      cell-line. Although apparent cytopathic effect was not observed in the virally
      infected cell line, the infectious virus with a high viral title was detected.
      The cell line had been passed for more than 30 generations and no significant
      difference in viral title was observed among generations 10, 20 and 30 after
      PRRSV infection. CONCLUSION: Transfection of non-permissive PK-15 cells with
      porcine CD151 cDNA conferred the susceptibility to PRRSV infection, indicating an
      important role of the porcine CD151 in PRRSV infection of porcine cells.

PMID- 23957157
TI  - [Effect of ZnSO4 on L-lactic acid production by Rhizopus oryzae].
AB  - OBJECTIVE: To improve the yield and quality of L-lactic acid by Rhizopus oryzae,
      we aim to understand the relationship between inorganic salts utilization and the
      L-lactic acid metabolism of the strain RLC41-6, through systematic analysis of
      the effects of zinc ion concentration on the production of L-lactic acid and the
      Lactic Dehydrogenase (LDH) activity. METHODS: Rhizopus oryzae was cultured at 36
      degrees C for 36h with different quantity of ZnSO4 in fermentation medium. The
      fermentation products were monitored by reversed-phase high performance liquid
      chromatography (RP-HPLC), LDH isoenzyme composition in the cell was analysed by
      non-denatured polyacrylamide gel electrophoresis (PAGE). RESULTS: Our results
      showed that the concentration of ZnSO4 in medium could modulate the expression of
      LDH isoenzyme except LDH1, especially stimulated the expression of LDH4 and LDH5.
      When initial concentration of ZnSO4 is above 0.02%, the LDH4 and LDH5 reached the
      highest level. However, the activity of LDH was inhibited by higher concentration
      zinc ion in extracellular environment. When ZnSO4 concentration is 0.02%, LDH
      activity reaches its maximum 200U/mL, the HPLC assay showed only L-lactic in the
      fermentation products (137 g/L), while the conversion rate of glucose to lactic
      acid is 91%. CONCLUSION: Zinc ion can regulate the metabolic processes of
      Rhizopus oryzae and modulate the types of the final fermentation products. An
      optimal concentration of ZnSO4 can not only facilitate the LDH expression but
      also prevent pyruvate from transformation into the malic acid and fumaric acid
      during the metabolism process, thereby enhance the metabolism of glucose to
      lactic acid of Rhizopus oryzae.

PMID- 23957158
TI  - [Influence of flocalin on development of apoptosis and necrosis at anoxia
      reoxygenation of culture rats neonatal cardiomyocytes].
AB  - The influence of the new cardioprotector flocalin was investigated on the culture
      of rat's neonatal cardiomyocytes during anoxia-reoxygenation modelling. The
      mechanisms of apoptosis and necrosis were investigated under influence of ATP
      sensitive potassium (K(ATP)) channels activation and in conditions of blocking of
      the L-type calcium (VGCCs) channels. Flocalin was added in the culture medium in
      the dose 5 and 20 microM at 2 minutes before anoxia (30 minutes) and following
      reoxygenation (60 minutes). These doses are near to: the first dose means the
      opening of K(ATP) channels and the second one means the IC50 block of VGCCs. It
      is discovered that in dose 5 microM of flocalin drew the change of correlation of
      living, necrotizing and apoptizing cells drew side-shifting living. The number of
      live cells was almost the same like in control (experiments without anoxia
      reoxygenation modelling). The opening of K(ATP) channels decreases necrosis in
      two times and fully prevented development of apoptosis which was induced anoxia
      reoxygenation modelling. Flocalin depressed the apoptosis of neonatal
      cardiomyocytes so that he was on to 36% less than in control group (without
      anoxia-reoxygenation). But in the high dose (20 microM) that provokes not only
      K(ATP) channels opening but also IC50 block of VGCCs cardioprotection was not
      detected after modelling of anoxia-reoxygenation. The last can be investigation
      both enough strong activating of the potassium channels and by investigation of
      both factors are opening of potassium and inhibition of VGCCs channels and,
      accordingly, substantial diminishing of level of introcellular Ca2+ and violation
      of metabolic processes yet to anoxia-reoxygenation. Thus, small doses of
      flocalin, that induce moderate opening of K(ATP) channels significantly decrease
      the number of necrotic and apoptotic cells in culture of rat neonatal
      cardiomyocytes induced by anoxia-reoxygenation.

PMID- 23957159
TI  - [Cardiomyocyte differentiation of individual clones murine induced pluripotent
      stem cells].
AB  - Cardiomyocyte differentiation of certain clones of murine induced pluripotent
      stem cells (iPS) was estimated. iPS were obtained due to reprogramming of murine
      embryonic fibroblasts with transposon-based Sleeping beauty plasmids as sene
      delivery systems. Differentiation was performed in suspension culture and in
      attached to tissue-culture plates embryoid bodies (EBs). Ascorbic acid was
      applied as inductor. According to the obtained results, the differentiation was
      tenfold more effective in attached EBs. Ascorbic acid stimulated the generation
      of cardiomiocytes.

PMID- 23957160
TI  - [Ionic mechanisms of carbon monoxide action on the contractile properties of
      smooth muscles of the blood vessels].
AB  - Carbon monoxide (CO) is one of a family of gas transmitters. In this article we
      present the results of mechanographic investigations of the mechanisms of CO
      action on a rat thoracic aorta segments. We found that relaxing effect of CO
      donor CORM-2 on vascular smooth muscles is mediated mainly by opening of voltage
      dependent potassium channels in smooth muscle cells: 4-aminopyridine, blocking
      these channels, almost completely eliminated the CO-induced vasorelaxation of the
      segments precontracted by depolarization of the smooth muscle cells membranes
      with high potassium (30 mM KCl) solution or by phenylephrine (10 microM). For the
      first time we documented that CORM-2 reduces the nicardipine-sensitive input of
      45Ca2+ in freshly isolated aorta cells. There are reasons to suggest that the L
      type voltage-dependent calcium channels of vascular smooth muscle cells are
      another target for CO, which is implemented in the relaxing effect of this gas
      transmitter. Additional research is needed to determine the influence of
      ruthenium complexes (Ru(II)) on phenomenology of carbon monoxide effects.

PMID- 23957161
TI  - [Changes in the kinetics of calcium signals in response to high frequency
      stimulation in the cultured hippocampal neurons].
AB  - Dynamic changes in the intracellular free Ca2+ concentration ([Ca2+]i) were
      studied in hippocampal cultured neurons using fluorescent Ca(2+)-indicator dye
      Indo-1 and somatic whole-cell recordings. During the tetanus stimulation Ca(2+)
      transient increased their amplitude up to a steady-state level during repetitive
      stimulation. We identified two groups of neurons based on Ca-signal dynamics
      after the end of stimulation: the first group (n = 24) with the monoexponential
      decay of [Ca2+]i direct after the end of the tetanus; the second group (n = 32)
      with the monoexponential delayed [Ca2+]i decay after the end of the tetanus, the
      duration of delay varied from 1 to 27 s and depended on duration and frequency of
      stimulation. Peak amplitudes of Ca(2+)-transients were statistically different
      between the first (1820 +/- 195 nM, n = 24) and the second (2618 +/- 165 nM, n =
      23) groups. A linear dependence between decay time constant and frequency of
      stimulation was found for the second group of neurons only. In all cases when the
      delayed decay was observed the decay time constant changed reliably after
      emergence of delayed decay; the average rise made up 41 +/- 8%. We suggest
      dynamic changes and essential rise in the intracellular free Ca2+ concentration
      arise from the presence of intracellular low-affinity buffer. This statement is
      to be further tested using pharmacological approach.

PMID- 23957162
TI  - [Effects of diphenyl derivatives on electrophoretic mobility of murine T
      lymphocytes].
AB  - The early changes of electrophoretic mobility (EPM) of murine T lymphocytes
      induced by structural analogues of amixine-dihydrochloryde 4,4'-bis
      [2(diethylamino)ethoxy]diphenyl (compound 1) and dihydrochloryde 2
      methoxycarbonil-4,4'-bis-[2(diethylamino)ethoxy]diphenyl (compound 2) were
      studied by electrophoresis technique. During the interval 0-2 hours all compounds
      increased the absolute values of EPM in comparison with control. These changes
      were of the same kind--distinctions were quantitative. Amixine and compound 1
      during the interval 2-4 hours additionally increased the EPM. The compound 2, on
      the contrary, decreased the EPM. It was shown that the opposite effects of the
      aforementioned compounds were caused by the fact that amixine and compound 1
      induce, and compound 2 does not induce IFN production in T lymphocytes in vitro.
      The results of our experiments are important for understanding of the mechanisms
      of immunomodulating effect of amixine and its structural analogues.

PMID- 23957163
TI  - [The effect of amlodipine, bisoprolol on the myocardial ultrastructure of the
      hypertensive rats].
AB  - Calcium channel blockers and beta1-adrenoblockers are effective antihypertensive
      agents, but their cell protective properties are not investigated well.
      Spontaneously hypertensive rats received a 10 mg/kg/day amlodipine dose and 25
      mg/kg/day bisoprolol dose via an orogastric tube during three months. We
      performed examination of the myocardium's fragments under a scanning electron
      microscope. Morphometric investigation of mitochondrions we performed using
      special program what is named "ORGANELLE". Amlodipine significantly normalizes
      the ultrastructure of the myocardium. This antihypertensive drug prevented the
      signs of over-contractility of myofibrils. Amlodipine causes the fusion
      mitochondrions which has compensatory character on the background of good safety
      of mitochondrial ultrastructures. Another feature of amlodipine is a significant
      increase in the number of capillaries. Bisoprolol significantly reduced over
      contractility of the myofibrils, but the signs of dystrophic-destructive
      processes in myofibrils and mitochondrions of cardiomyocytes remained. Bisoprolol
      improved the condition of the endothelial cells, but the activation of the
      functional activity of these cells has not been observed. The combined use of two
      antihypertensive drugs amlodipine and bisoprolol led to a better recovery of
      myofibrils than their separate use, whereas the effect on mitochondrions noted
      similar as in the group of rats received bisoprolol and that effect was worse
      than during amlodipine's monotherapy. Also we didn't reveal a reason to combine
      these drugs after analysis of the effect of the drug combination on the
      conditions of blood microvessels, which number was increased compared with
      hypertensive rats, but significantly less than when rats received only
      amlodipine. These essential cell-protective effects of amlodipine and bisoprolol
      in spontaneously hypertensive rats could be a significant additional factor in
      the treatment of hypertension complicated with pathological changes in the heart.

PMID- 23957164
TI  - [Mechanisms of nephrotoxicity of novel anticancer compound maleimide derivative
      MI-1].
AB  - The features of the impact of the maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4
      (CF3-fenilamino)-1H-pyrrole-2,5-dione (MI-1) on the viability and apoptosis
      induced cell death of renal proximal and distal tubular epithelial cells and the
      amount of total and phosphorylated ERK1/2 were studied in order to establish
      possible mechanisms of nephrotoxicity induced by of MI-1. The viability and
      apoptosis of renal epithelial tubular cells after incubation with MI-1 were
      perfomed by 3,4,5-dymetyltiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT)-test
      and by flow cytometry after staining with specific antibodies to annexin V,
      respectively. The amount of ERK 1/2 was determined by Western blotting. The data
      indicate that MI-1 was more toxic with respect to the epithelial cells of distal
      than proximal tubule cells. The apoptosis-induced cell death pathway is involved
      in the mechanisms of MI-1 cytotoxicity. One of the possible mechanisms of MI-1
      nephrotoxicity is increase in phosphorylation of ERK1/2 in the distal tubules. At
      the same time the increase amount of total ERK1/2 in proximal tubules under the
      influence of MI-1 may contribute to the survival of proximal tubular epithelial
      cells under the impact of a toxic factor or oxidative stress.

PMID- 23957165
TI  - [Pharmacological correction of experimental mitochondrial dysfunction of brain
      stem neurons by rhytmocor and mildronate].
AB  - The results of pharmacological correction of experimental mitochondrial
      dysfunction in brain stem neurons after single injection of specific respiratory
      complex I inhibitor rotenone by complex agents mildronate and rhytmocor have been
      presented. It was shown that 14-days rhytmocor injection promoted the rise of
      mitochondrial reserve capacity under glutamate and malate oxidation as well as
      under succinate oxidation. The mildronate injection was accompanied by
      enhancement of the velocity of phosphorilated mitochondrial respiration in the
      presence and absence of ADP when both substrates of oxidation were used. Under
      the brain stem experimental mitochondrial dysfunction, mildronate improved a
      decreased velocity of phosphorilated mitochondrial respiration and the
      respiratory control in a more significant degree under glutamate malate as the
      substrates of oxidation. Simultaneous increase in the respiratory control and in
      the coefficient of efficacy ofphosphorilation during the correction of
      experimental mitochondrial dysfunction by rhytmocor could suggest about essential
      economization of processes in mitochondrial respiratory chain. It was concluded
      that the main mechanisms of influence on mitochondrial disturbances of both
      agents were connected to the powerful rise of NAD-related oxidation which allowed
      to enhance a resistance of mitochondrial respiratory chain and to optimize the
      mitochondrial function.

PMID- 23957166
TI  - [The influence of normobaric hypoxia on the morphofunctional changes of thyroid
      gland in young rats].
AB  - We investigated the influence of hypoxic gas mixture (the different modes) on the
      morphometric indexes of thyroid gland functional activity in 3-mounth rats. It
      was shown a decrease in the size of follicles of middle area and the colloid and
      an increase in the amount of thyrocytes in a follicle, resorption vacuoles and
      interfollicular epithelium after exposure to hypoxic gas mixture (10% oxygen). We
      also detected an increase in a follicle-colloid index and a decrease in the
      colloid accumulation index. Thus, a dosed normobaric hypoxia intensifies the
      functional activity and physiological regeneration processes of thyroid gland in
      the young animals.

PMID- 23957167
TI  - [Deformability of the erythrocytes membrane in rats of different age in hypoxia].
AB  - Using modern ("laser tweezers", low ionic strength Liss, definition of
      microviscosity of erythrocyte membranes by fluorescence probe pyrene) and
      classical methods of investigation the osmotic resistance of red blood cells and
      protein membrane of red blood cells, the authors have esteblisheshed that
      deformation of the red blood cells in hemic hypoxia varies depending on the
      animals' age. The maximum capacity of red blood cells to deform was detected in
      rats of prepubertal period (40.2%). In the group of old rats this parameter
      reached the minimum level (19.7%). Age changes in erythrocyte membranes during
      hypoxia are manifested in an increase in the viscosity of the lipid bilayer
      (microviscosity index reduced in old rats compared with young adult animals by
      69.5%) and an increase in the percentage of skeletal protein spectrin (by 53.0%).
      These changes determine the reduction in deformation capacity of red blood cells.
      The relationship between the age-related changes of erythrocyte membrane
      deformation and the state of regional microcirculation has been determined. In
      old rats a perfusion volume is reduced by 43.8%, the fractional volume of red
      blood cells passing per unit time through microvessels reduced by 59.3%, the
      proportion of oxygen consumption in tissues decreased by 6.6% and the perfusion
      of oxygen saturation decreased by 50.0%.

PMID- 23957168
TI  - [Functional state of the ileum, cationic peptids and zinc content in the Paneth
      cells of the rats following lincomycin, indomethacin and methotrexate
      andministration].
AB  - In the paper the relation between the changes of a functional condition of ileum,
      composition of its microflora and secretory activity of Paneth cells has been
      investigated. Administration of lincomycin led to a reduction of total of
      symbiotic bacteria and appearance of opportunistic microflora. Statistically
      insignificant changes of speed of transit of intestinal contents and damage of
      barrier function of an intestinal epithelium were noted. The intestinal
      epithelium was characterized by signs of inflammation. Administration of
      indomethacin and methotrexate led to significant changes of a functional state of
      a small intestine of rats. The speed of transit of intestinal contents following
      indomethacin administration increased by 30%, and, on the contrary, decreased by
      90% following administration of methotrexate. The ability of epithelium of ileum
      to adsorb vital dye in both cases increased (by 32 and 51%, respectively)
      indicating the damage of barrier function. Thus there were significant changes in
      structure of microflora of ileum: reduction of quantity symbiotic and emergence
      of opportunistic microflora, a translocation of bacteria to a mucous wall. It was
      concluded that animal of all three experimental groups had a reduction of the
      contents of cationic proteins and zinc in the secretory granules of Paneth cells.
      These results can testify that balance changes between simbiotic and
      opportunistic microflora are a factor which has an impact on intestine damage and
      also causes activation of secretory function of Paneth cells.

PMID- 23957170
TI  - [The dynamic of annual modification of phasic structure of cardiac cycle in
      children of junior school age].
AB  - By using of the method of tetrapolar impedance rheopletysmography we studied the
      phasic structure of cardiac cycle in children of junior school age. We have shown
      that a decrease of cardiac cycle duration in children is due to a decrease of the
      common diastole duration, the mean fraction of which in children of six years is
      48.58% from the cardiac cycle duration. With age the duration of cardiac cycle
      increases. In 12 y.o. children this parameter is significantly higher (0.702 +/-
      0.020s) that that observed in 6 y.o. children (0.636 +/- 0.017s). The shortest
      duration of cardiac cycle is detected in 10 y.o. children (0.617 +/- 0.018 s).

PMID- 23957169
TI  - [Perception, processing of visual information and resistance to emotional
      stresses in athletes of different ages].
AB  - Among the numerous studies devoted to the study of perception and information
      processing, no data available on the effects of age on these processes. In this
      paper we studied the influence of psycho-emotional stress and different levels of
      stress on the mental processes of perception and information processing in highly
      skilled athletes divided into two groups. The first group included the athletes
      aged 19-24 years (12 athletes, members of the Ukrainian team in Greco-Roman
      wrestling), the second group included the athletes aged 27-31 years (7 highly
      skilled athletes, members of the Ukrainian team in Greco-Roman wrestling). We
      revealed that the athletes of the first group had higher productivity and better
      visual perception and visual information processing efficiency, compared with
      athletes from the second group. This observation suggests a dependency of
      cognitive component of perception and information processing on the age of the
      athletes. Sportsmen from the second group had higher stress resistance compared
      to the older age group.

PMID- 23957171
TI  - [The anti-inflammatory effect of fullerene C60 on adjuvant arthritis in rats].
AB  - The anti-inflammatory properties of non-modified fullerene C60 (FC60) by adjuvant
      arthritis in Wistar rats have been studied. It was shown that the intraperitoneal
      introduction of FC60 (50 ng) reveals an anti-inflammatory and chondroprotective
      actions in the phase of systemic manifestation of adjuvant arthritis. The effect
      was carried out by limitation of inflammation of damaged limb, normalization of
      body weight, the decrease in body temperature. Introduction of FC60 promote the
      reduction of leukocyte level, the erythrocyte sedimentation rate, concentrations
      of sialic acids and the ceruloplasmin levels, processes degeneration of
      cartilaginous tissues of the joint of rats. It has been concluded that the
      therapeutic effectiveness of non-modified FC60 in experimental adjuvant arthritis
      is comparable with the action of water-soluble forms of fullerenes. The results
      substantiate the future investigations of non-modified FC60 for design of
      therapeutic agents for treatment of rheumatoid arthritis in clinics.

PMID- 23957172
TI  - [Determination of age-related liver stiffness changes in rats according to the
      ultrasonic shear wave elastography].
AB  - We examined by ultrasound shear wave elastography (SWE) changes of liver
      stiffness (LS) in three groups rats of different ages. LS measurement by SWE was
      performed on "Ultima PA" equipment ("Radmir", Kharkov, Ukraine) with a 10-5 MHz
      linear transducer. To assess the functional state of the liver at the same time
      we studied age-related biochemical and morphological differences in the liver. A
      valid LS determination (success rate of at least 60%) was observed in 96.6%
      animals of different age groups. We observed statistically significant increasing
      of LS between 3-month and 20-month rats (p = 0.010), but its value in each group
      do not exceed normal or reference range. In article discussed possible connection
      between age-related changes of LS and state of connective tissue elements,
      functional activity, hydration, etc. It is concluded that shear wave elastography
      may be a new objective biophysical method for obtaining information about the
      state of the liver stiffness of the liver tissue.

PMID- 23957173
TI  - [Influence of Hepatomax on male fertility].
AB  - The features of morphotype sperm in men with infertility and found some monomodal
      its deviations. The study of products of lipid peroxidation (LPO) and antioxidant
      enzymes (AOP) levels in men with mild forms of chronic inflammation of the
      urogenital tract complicated with infertility. The studies found that the
      majority of men surveyed marked activation of lipid peroxidation of biological
      membranes, which was accompanied by increased concentrations of the major
      metabolite of LPO--intermediate (conjugated diene) and final (malondialdehyde) in
      serum. In the study of the system of AOP was found that the activity of catalase
      and superoxide dismutase decreased. Was calculated as an integrative index F,
      which characterizes the ratio of prooxidant and antioxidant properties of blood.
      Found suppression of the index, which indicates an imbalance indicators LPO/AOP.
      A negative correlation between the index F and the presence of mikrosomatich form
      sperm was found. The positive influence of the Hepatomax on the process of
      recovery oxidative activity systems, normalization of the integral index of F and
      reduce the number of abnormal forms of generative cells was established. Given
      antioxidant, immunomodulating, hepatoprotective properties of the Hepatomax, we
      consider it appropriate to include this drug in treatment of infertile men with
      inflammatory processes in the urogenital tract.

PMID- 23957174
TI  - [Mesenchymal stem cells and their immunological properties].
AB  - Mesenchymal stem cells (MSC) are found in a variety of tissues, including bone
      marrow, skin and adipose tissue and can be expanded easily in vitro. MSC are
      thought to have tissue regenerative properties, in the first place via their
      multilineage differentiation capacity. In addition, MSC have potent
      immunomodulatory capacity. They inhibit the proliferation of T cells and inhibit
      dendritic cell maturation. These properties make MSC promising for a diversity of
      clinical applications; for example, for the prevention and treatment of
      autoimmune diseases and bone marrow rejection. Different studies have attributed
      the immunosuppressive effect of MSC to different immunosuppressive factors. These
      include indoleamine 2,3-dioxygenase (IDO), HLA-G, nitric oxide, interleukines.
      The long-term ability of allogeneic MSCs to preserve function in the infarcted
      heart is limited by a biphasic immune response whereby they transition from an
      immunoprivileged to an immunogenic state after differentiation, which is
      associated with an alteration in major histocompatibility complex--immune antigen
      profile. These findings provide critical information about the immunosuppression
      of MSCs and for better application of MSCs in treating immune disorders.

PMID- 23957175
TI  - Infant and young child feeding: solid facts.

PMID- 23957176
TI  - Breastfeeding and the developing brain.

PMID- 23957177
TI  - The impact of the Baby Friendly Health Initiative in the Australian health care
      system: a critical narrative review of the evidence.
AB  - Studies have identified that the practices of maternity facilities and health
      professionals are crucial to women's experience of support and breastfeeding
      'success'. The Baby Friendly Hospital Initiative (BFHI) was launched globally in
      1991 to protect, promote and support breastfeeding. While a direct causal effect
      has not been established and critics suggest the rhetoric conflicts with women's
      lived experiences as new mothers, a positive association between the Initiative
      and breastfeeding prevalence is apparent. Internationally, impact studies have
      demonstrated that where the Initiative is well integrated, there is an increase
      in rates of breastfeeding initiation and, to a lesser extent, duration. In
      consideration of the known health risks associated with the use of artificial
      baby milks this would suggest that BFHI implementation and accreditation should
      be a desirable strategy for committed health facilities. However, a variation in
      both BFHI uptake and breastfeeding prevalence between nations has been reported.
      This narrative review critically discusses a variety of issues relevant to the
      uptake and support of breastfeeding and the BFHI, utilising Australia as a case
      study. Whilst it enjoys 'in principle' policy support, Australia also suffers
      from a lack of uniformity in uptake and perception of the benefits of BFHI at all
      levels of the health system. Australian and international studies have identified
      similar enablers and barriers to implementation.

PMID- 23957178
TI  - Breastfeeding mothers returning to work: experiences of women at one university
      in Victoria, Australia.
AB  - Working women need to juggle work, child care and family to continue to
      breastfeed. This qualitative study's aim was to explore women's experiences of
      returning to work following the birth of their baby. Focus groups were held with
      women within one multi-campus university, who had commenced breastfeeding at
      birth and had returned to work or study within 12 months. In addition, educators
      working with babies in childcare centres on two of the campuses were interviewed.
      Thematic analysis was employed used Rogoff's (2003) three planes of analysis, the
      individual, the interpersonal and the cultural-institutional. Three themes,
      proximity, flexibility, and communication, were identified relating to the
      factors impacting on women and their choices to breastfeed or wean on returning
      to work. From a socio-cultural perspective these themes can be understood as
      situated within the interrelated contexts of workplace, child care and family.
      Limitations of the study include the small number of participants and recruitment
      from one university.

PMID- 23957179
TI  - Breastfeeding information in pharmacology textbooks: a content analysis.
AB  - Women often need to take medicines while breastfeeding and pharmacists need to
      provide accurate information in order to avoid undue caution about the
      compatibility of medicines and breastfeeding. The objective of this study was to
      review information provided about breastfeeding in commonly used pharmacology
      textbooks. We asked 15 Australian universities teaching pharmacy courses to
      provide a list of recommended pharmacology textbooks in 2011. Ten universities
      responded, generating a list of 11 textbooks that we analysed for content
      relating to breastfeeding. Pharmacology textbooks outline the mechanisms of
      actions of medicines and their use: however, only a small emphasis is placed on
      the safety/compatibility of medicines for women during breastfeeding. Current
      pharmacology textbooks recommended by Australian universities have significant
      gaps in their coverage of medicine use in breastfeeding. Authors of textbooks
      should address this gap, so academic staff can recommend texts with the best
      lactation content.

PMID- 23957180
TI  - Maternal and infant sleep postpartum.
AB  - New parents should be aware that infants' sleep is unlike that of adults and that
      meeting their infant's needs is likely to disrupt their own sleep. They will need
      to adjust their routine to manage their own sleep needs. Parental sleep patterns
      in the postpartum period are tied to the infant's development of a circadian
      sleep-wake rhythm, and the infant's feeds. Close contact with the mother and
      exposure to light/dark cues appear to assist in the development of the infant's
      circadian rhythm. The composition of breastmilk varies over the course of 24
      hours and some components produced at night are likely to contribute to the
      infant's day/night entrainment. There is no clear evidence that using artificial
      feeds improves maternal sleep. Most infants need night feeds but requirements for
      nighttime feeds vary with the individual.

PMID- 23957181
TI  - Childhood obesity and being breastfed.

PMID- 23957182
TI  - Focus on transparency: helping patients and consumers make informed decisions.

PMID- 23957183
TI  - 5 ways to be a strong leader in challenging times.

PMID- 23957184
TI  - Using business intelligence to manage supply costs.
AB  - Business intelligence tools can help materials managers and managers in the
      operating room and procedural areas track purchasing costs more precisely and
      determine the root causes of cost increases. Data can be shared with physicians
      to increase their awareness of the cost of physician preference items. Proper use
      of business intelligence goes beyond price benchmarking to manage price
      performance over time.

PMID- 23957185
TI  - Workers' compensation--the other self-insured liability.
AB  - Self-insured healthcare entities should take the following steps to understand,
      report, and control their exposure to workers' compensation losses: Focus on
      safety and risk management. Maintain a proper retention. Create'skin in the game"
      through an allocation. Benchmark the program's performance. Perform frequent
      analyses and obtain second opinions.

PMID- 23957186
TI  - John Kitzhaber: on achieving healthcare transformation.

PMID- 23957187
TI  - The big deal about big data.
AB  - Big data is a concept that is being widely applied in the retail industries as a
      means to understand customers' purchasing habits and preferences for followup
      promotional activity. It is characterized by vast amounts of diverse and rapidly
      multiplying data that are available at or near real-time. Conversations with
      executives of leading healthcare organizations provide a barometer for
      understanding where the industry stands in its adoption of big data as a means to
      meet the critical information requirements of value-based health care.

PMID- 23957188
TI  - Engaging purchasers in value improvement.
AB  - Health systems that wish to engage employers and other healthcare purchasers
      directly in initiatives to improve health should consider a number of steps,
      including: Setting a reasonable goal around a critical mass of covered lives the
      health system could attract and maintain through such an approach. Finding
      likeminded customers and partners. Anticipating competitive responses from the
      market. Creating a distinctive brand.

PMID- 23957189
TI  - Using nursing resource teams to improve quality of care.
AB  - The process of setting up and monitoring nursing resource teams for maximum
      effectiveness involves five key steps: Set the resource team goals and approach.
      Plan for development and oversight. Gather and analyze the relevant information.
      Deploy the team. Reevaluate staffing levels and effectiveness.

PMID- 23957190
TI  - The value of understanding patient referral flow.
AB  - A referral tracking system can help a health system achieve five strategic
      objectives: Track referrals to and from employed physicians. Improve clinical
      outcomes and patient satisfaction. Identify physicians who are specialists of
      choice--and those who are not. Enhance and refine the medical staff development
      planning process. Improve the accuracy of utilization and financial forecasts.

PMID- 23957191
TI  - The ROI of engaged patients.
AB  - Summa Health System, based in Akron, Ohio, implemented pre-visit multimedia
      engagement and post-visit centralized follow-up as a means to promote the more
      active engagement of its patients in managing their care. The initiative led to
      significant improvements in the patient experience, as measured by HCAHPS
      ratings. The initiative, among others, also helped ensure that Summa received 100
      percent of its 2012 pay-for-performance incentive from the Centers for Medicare &
      Medicaid Services.

PMID- 23957192
TI  - Using normalized RVU reporting to evaluate physician productivity.
AB  - Relative value units (RVUs) were developed by the Centers for Medicare & Medicaid
      Services (CMS) to establish a value for each physician service categorized by a
      current procedural terminology code. For some time, RVUs provided an effective
      tool for measuring physician productivity, until CMS decided to adjust RVU
      weightings annually, undermining the tool's comparative effectiveness. A new
      model developed by the clinical practice management plan serving Stony Brook
      Medicine University Physicians in Stony Brook, N.Y., provides a means to
      normalize RVUs from year to year, thereby making RVUs again useful for assessing
      physician productivity.

PMID- 23957194
TI  - Finding a CMO who can drive value.

PMID- 23957193
TI  - 6 strategies for managing value in uncertain times.
AB  - To maintain their creditworthiness in a volatile market and prepare for changes
      ahead, middle-market hospitals are: Cutting costs beyond the low-hanging fruit.
      Preparing for population health management. Integrating with physicians and
      growing their primary care networks. Expanding outpatient services. Reviewing
      their merger and acquisition options and affiliating when it makes sense.
      Investing in IT.

PMID- 23957195
TI  - What's next for the ACA? It depends.

PMID- 23957196
TI  - Pituitary adenomas in childhood and adolescence.
AB  - Scientific advances are revealing the complexity of pituitary development, which
      is controlled by multiple transcription factors and signaling molecules.
      Unregulated pituitary cell growth, resulting in pituitary adenoma, is usually
      sporadic and results from monoclonal expansion of a single mutated cell. However,
      some adenomas develop as part of a genetic syndrome. Prolactinoma is the most
      common hormonally active pituitary adenoma in children. The non-functioning (non
      secreting) pituitary adenoma is the second most common and often stains positive
      for GH, PRL, and/or TSH. While Cushing disease, resulting from an ACTH-secreting
      adenoma, commonly manifests as weight gain with growth deceleration in children,
      GH excess causes gigantism with rapid, accelerated growth inappropriate for the
      height of the family. TSH secreting pituitary adenomas are rare, and biochemical
      analysis will show an elevated thyroxine level with a non-suppressed or high TSH.
      Though the natural history of pituitary incidentalomas in children is unknown,
      adult practice guidelines are established.

PMID- 23957197
TI  - IGF-I deficiency and hearing loss: molecular clues and clinical implications.
AB  - Sensorineural hearing loss is a clinical heterogeneous disorder and a significant
      health-care problem with tremendous socio-economic impact. According to WHO,
      "Over 5% of the world's population has disabling hearing loss -328 million adults
      and 32 million children-". In children, early hearing loss affects language
      acquisition. Hearing deficits are generally associated with the loss of the
      sensory "hair" cells and/or neurons caused by primary genetic defects or
      secondary to environmental factors including infections, noise and ototoxic
      drugs. Hearing loss cannot be reversed and currently the available treatment is
      limited to hearing aids and cochlear implants. Studies are being conducted to
      develop alternative treatments combining both preventive and reparative
      strategies. Human insulin like growth factor (IGF) I deficiency is a rare disease
      associated with hearing loss, poor growth rates and mental retardation
      (ORPHA73272, OMIM608747). Similarly, lgf1-/- mice are dwarfs with poor survival
      rates and congenital profound sensorineural deafness. IGF-I is known to be a
      neuroprotective agent that maintains cellular metabolism, activates growth,
      proliferation and differentiation, and limits cell death. Here we will discuss
      the basic mechanisms underlying IGF-I actions in the auditory system and their
      clinical implications to pursue novel treatments to ameliorate hearing loss.

PMID- 23957198
TI  - Novel mechanisms of regulation of IGF-1R action: functional and therapeutic
      implications.
AB  - The IGF-1R pathway is essential for the initiation and progression of many
      cancers. In contrast to other receptor tyrosine kinases involved in cancer, it is
      not frequently mutated or amplified. The classical model of signaling through the
      IGF-1R centers on ligand initiated kinase activation, allowing binding of adaptor
      molecules and downstream activation of the MAPK and PI3K pathways. The signaling
      is terminated through receptor ubiquitination and subsequent degradation. To
      date, therapies targeting IGF-1R have been designed solely aiming to block
      phosphorylation mediated signaling by preventing receptor-ligand interaction or
      by limiting kinase activation. Yet, the classical model is insufficient to
      explain receptor behavior induced by some IGF-1R inhibitors. This review
      advocates an updated model of IGF-1R signaling, accommodating the "classical"
      kinase signaling and the IGF-1R-kinase independent signaling thus providing the
      theoretical background for receptor downregulation induced by IGF-1R inhibitors.
      This model should be considered for future design of effective therapies
      targeting the IGF-1R pathway.

PMID- 23957199
TI  - Vitamin D in childhood cancer: a promising anticancer agent?
AB  - Children diagnosed and treated for cancer are vulnerable to Vitamin D deficiency
      depending on many factors. The Vitamin D status in children with cancer has been
      mostly regarded as a contributory factor for skeletal pathologies so far.
      However, the calcitriol was found to promote cell differentiation, inhibit
      malignant proliferation, and exhibit antiinflammatory, proapoptotic and
      antiangiogenic properties. In addition to this, numerous epidemiological studies
      link Vitamin D and cancer and indicate to possible role of Vitamin D in cancer
      pathogenesis and progression. This article aims to provide an overview of the
      possible role of Vitamin D deficiency in childhood cancer in terms of prevention
      and treatment.

PMID- 23957200
TI  - Determination of C-peptide in children: when is it useful?
AB  - Diabetes results from insulin deficiency but despite this endogenous insulin
      secretion is infrequently measured. C-peptide is not present in synthetic insulin
      so it's presence indicates endogenous secretion. One of the key roles for
      measuring C-peptide in childhood is to assist in the diagnosis of diabetes
      subtypes, which in turn determines appropriate management. It is also useful in
      Type 1 diabetes to monitor disease course, both in clinical practice and in
      trials following intervention with disease modifying agents. Measuring C-peptide
      routinely in Type 1 diabetes provides valuable information to the patient and
      clinician about glucose variability, risk of hypoglycemia and ketoacidosis. Newer
      more practical methods of C-peptide determination are now available to allow
      assessment of endogenous insulin secretion in routine clinical practice. We
      review the physiology of insulin secretion, the essential roles and methods for C
      peptide determination in blood and in urine.

PMID- 23957201
TI  - P38 activation is more important than ERK activation in lung injury induced by
      prolonged hyperbaric oxygen.
AB  - Prolonged exposure to hyperbaric oxygen can cause pulmonary and nerve system
      toxicity. Although hyperbaric oxygen treatment has been used for a broad spectrum
      of ailments, the mechanisms of prolonged hyperbaric oxygen-induced lung injury
      are not fully understood. The purpose of the present work was to investigate the
      roles of ERK, p38, and caspase-3 in rat lung tissue exposed to hyperbaric oxygen
      at 2.3 atmospheres absolute (atm abs) for two, six and 10 hours. The results
      showed that the ERK and p38 were phosphorylated at two hours and reached a peak
      at six hours into exposure to hyperbaric oxygen. While the phosphorylation level
      of ERK decreased, p38 remained at a high level of activation at 10 hours. The
      activation of ERK and p38 was down-regulated when rats were exposed to normoxic
      hyperbaric nitrogen for 10 hours. However, caspase-3 was activated at six hours
      and 10 hours into exposure to hyperbaric oxygen. These results demonstrated
      different changes of activation of ERK and p38 during lung injury induced by
      prolonged exposure to hyperbaric oxygen. The time course changes of activated
      caspase-3 were similar to the process of p38 activation upon exposure to
      hyperbaric oxygen. In this way, activation of p38, not ERK, seems to be a
      mechanism associated with prolonged hyperbaric oxygen-induced lung injury.

PMID- 23957202
TI  - Blood pressure, acid-base and blood gas status and indicators of oxidative stress
      in healthy male rats exposed to acute hyperbaric oxygenation.
AB  - Different protocols of hyperbaric oxygenation (HBO2) are used for research
      purposes; however, data on the changes in blood pressure, oxidative stress and
      acid-base and gas status induced by various oxygenation protocols are scarce and
      conflicting. The aim of this study was to examine the effects of an acute session
      of HBO2 [2 bar (200 kPa) for two hours] on arterial systolic and diastolic blood
      pressure, arterial blood gases and acid-base status, and oxidative stress in
      rats. Sprague-Dawley rats (12-15 weeks) were examined prior to, immediately and
      24 hours after a two-hour HBO2 exposure at 2 bars. The femoral artery was
      cannulated to determine blood pressure, and blood samples were collected to
      measure blood gases and acid-base status, Ferric reducing antioxidant power
      ability of plasma (FRAP) and thiobarbituric acid reactive substances (TBARS).
      Immediately after HBO2 systolic and diastolic blood pressure significantly
      decreased (from 138 +/- 14/103 +/- 13 to 113 +/- 12/72 +/- 16 mmHg). However,
      these values were still inside the normal physiological range. pH decreased (from
      7.34 +/- 0.05 to 7.28 +/- 0.05), pCO2 decreased (from 7.07 +/- 0.89 to 5.76 +/-
      0.50 kPa), pO2 increased (from 12.48 +/- 0.88 to 13.68 +/- 2.4 kPa), plasma
      bicarbonate decreased (from 27.04 +/- 3.25 to 20.52 +/- 3.02 mmol/L). Exposure to
      HBO2 immediately increased TBARS levels (from 0.17 +/- 0.09 to 21.79 +/- 1.05
      microM/MDA), while FRAP levels were not significantly changed. Measurements on
      separate animals 24 hours after a single HBO2 exposure showed no differences in
      comparison to control animals, except for pO2, which was significantly lower
      (11.10 +/- 0.31 kPa). The results define values of important parameters, serving
      as a necessary basis for complex analysis of HBO2 effects in research on rat
      animal models.

PMID- 23957203
TI  - Effects of simulated heliox diving at high altitudes on blood cells, liver
      functions and renal functions.
AB  - The aim of the present study was to examine the effects of simulated heliox
      diving at high altitudes on divers' blood cells, liver functions and renal
      functions. In this experiment, four divers lived for nine consecutive days in a
      dual-function high-low pressure chamber, which simulated air pressure at an
      altitude of 3,000 meters and at a 30-meter depth; an altitude of 4,000 meters and
      30-meter depth; and at an altitude of 5,200 meters and 30 meters and 50 meters in
      depth. Total time underwater was 60 minutes. The subjects breathed heliox (with
      oxygen at 40% and helium at 60%) during the simulated 30-meter dive from zero
      altitude to 30 meters and while remaining underwater; they breathed air while
      ascending from 30 meters to 18. They breathed heliox (with oxygen at 26.7% and
      helium at 73.3%) in the simulated dive from zero altitude to 50 meters
      underwater, in remaining underwater and in ascending from 50 meters to 29; air
      while ascending from 29 meters to 18. Pure oxygen was breathed while ascending
      from 18 meters to the surface; then air. Results indicated: (1) the correlating
      indices of routine blood, liver and renal functions, and urine routine were all
      within normal reference ranges; and (2) the indices tested at other periods of
      time were not significantly different (p > 0.05) from the results at zero-meter
      level and 3,000-meter level. The study suggests that the heliox diving processes
      at different high altitudes simulated in this experiment have no significant
      impact upon divers' blood routine, liver functions and renal functions.

PMID- 23957204
TI  - Evolution of the ventilatory function of professional divers over 10 years.
AB  - INTRODUCTION: The study was aimed at assessing changes in respiratory function
      after 10 years of professional diving. MATERIAL AND METHODS: A retrospective
      study was performed on divers who underwent an initial visit and a visit 10 years
      later at the same medical center. Pulmonary function tests were performed in the
      same laboratory with the same operating standards and using a Jaeger MasterBody
      plethysmograph. Each subject acted as his own control. The data were analyzed by
      Student's t-test and Spearman's correlation coefficient. RESULTS: Thirty-three
      divers were included. Changes over 10 years included: decreases in the forced
      expiratory flow rates at 75% (-0.65 liters/second) (p < 0.01) and at 50% (-0.51
      L/s) (p < 0.01) of forced vital capacity; significant decrease of the FEV1/FVC
      ratio (-3.4) (< 0.01); significant increases in total lung capacity (+0.32 L) (p
      = 0.03). The lung transfer factor for carbon monoxide (TL(CO)) had decreased
      significantly (-1.16 mmol/minute/kPa) (p = 0.02). The amount of smoking was
      significantly correlated with changes in slow vital capacity (R = 0.89; (p <
      0.01). Changes in the FEV1/ FVC ratio were correlated with the mean duration of
      the dives (R = -0.59; (p < 0.01) and with the number of dives during the 10 years
      (R = -0.42; p = 0.04). CONCLUSION: With increasing length of diving activities
      service, the pulmonary function displays a trend toward both a decrease in TL(CO)
      and a bronchial obstruction, extending to bronchi of increasing size.

PMID- 23957205
TI  - Incidence of DCS and oxygen toxicity in chamber attendants: a 28-year experience.
AB  - Decompression sickness (DCS) and central nervous system oxygen toxicity are
      inherent risks for "inside" attendants (IAs) of hyperbaric chambers. At the
      Hyperbaric Medicine Center at the University of California San Diego (UCSD),
      protocols have been developed for decompressing IAs. Protocol 1: For a total
      bottom time (TBT) of less than 80 minutes at 2.4 atmospheres absolute (atm abs)
      or shallower, the U.S. Navy (1955) no-decompression tables were utilized.
      Protocol 2: For a TBT between 80 and 119 minutes IAs breathed oxygen for 15
      minutes prior to initiation of ascent. Protocol 3: For a TBT between 120-139
      minutes IAs breathed oxygen for 30 minutes prior to ascent. These protocols have
      been utilized for approximately 28 years and have produced zero cases of DCS and
      central nervous system oxygen toxicity. These results, based upon more than
      24,000 exposures, have an upper limit of risk of DCS and oxygen toxicity of
      0.02806 (95% CI) using UCSD IA decompression Protocol 1, 0.00021 for Protocol 2,
      and 0.00549 for Protocol 3. We conclude that the utilization of this methodology
      may be useful at other sea-level multiplace chambers.

PMID- 23957206
TI  - Potential roles of hyperbaric oxygenation in the treatments of brain tumors.
AB  - Over the past 50 years hyperbaric oxygen (HBO2) therapy has been used in a wide
      variety of medical conditions, and one of them is cancer. Many clinical studies
      have been conducted to evaluate potential therapeutic effects of HBO2 as a part
      of cancer treatment. This review briefly summaries the potential role of HBO2
      therapy in the treatment of malignant tumors and radiation injury of the brain.
      HBO2 therapy is used for the enhancement of radiosensitivity in the treatment of
      some cancers, including malignant brain tumors. Radiotherapy within 15 minutes
      following HBO2 exposure, a relatively new treatment regimen, has been studied at
      several institutes and has demonstrated promising clinical results for malignant
      gliomas of the brain. HBO2 therapy also increases sensitivity to some
      antineoplastic agents; non-randomized clinical trials using carboplatin-based
      chemotherapy combined with HBO2 show a significant advantage in survival for
      recurrent malignant gliomas. The possibilities of combining HBO2 therapy with
      radiotherapy and/or chemotherapy to overcome newly diagnosed and recurrent
      malignant gliomas deserve extensive clinical trials. HBO2 therapy also shows
      promising potential for the treatment and/or prevention of radiation injury of
      the brain after stereotactic radiosurgery for brain lesions. The possibilities
      with HBO2 to enhance the therapeutic effect of irradiation per se, and to even
      increase the radiation dose if there are ways to combat the side effects, should
      boost new scientific interest into the whole field of oncology looking for new
      armamentaria to fight cancer.

PMID- 23957207
TI  - Case report: clearance to dive for a naval candidate with family history of
      malignant hyperthermia.
AB  - INTRODUCTION: A 20-year-old male military recruit who presented for a screening
      physical for U.S.Naval Diving Duty was found to have family history significant
      for malignant hyperthermia. He had never been exposed to anesthesia, a trigger
      for the condition, and had not undergone testing. Medical history was otherwise
      unremarkable, and the patient was cleared for diving. METHODS: Literature search
      was conducted using PubMed/Medline. Keywords included malignant hyperthermia,
      exertional heat illness, exertional rhabdomyolysis, diving, special operations,
      military. Results that included cases of malignant hyperthermia were included.
      RESULTS: Review of the literature reveals that malignant hyperthermia is primary
      a pharmacogenetic disorder limited to specific anesthetics, with rare reports of
      environmental triggers. Analysis of the disease, as well as the absence of
      reported cases of malignant hyperthermia in diving, suggest there is minimal
      increased risk in diving for subjects without history of exercise intolerance.
      CONCLUSION: Individuals with presumed or proven malignant hyperthermia
      susceptibility seeking activity clearance should be given precautions and undergo
      careful questioning for history of heat- or exercise-related illness. If
      negative, it seems reasonable to allow the patient participation in recreational
      or technical diving.

PMID- 23957208
TI  - What can normal gait biomechanics teach a designer of lower limb prostheses?
AB  - Compensating a limb loss with prosthesis is a challenging task due to complexity
      of the human body which cannot be fully matched by the available technical means.
      Designer of lower limb prostheses wants to know what specification of the device
      could provide the best approximation to the normal locomotion. Deep understanding
      of the latter is essential, and gait analysis may be a valuable tool for this.
      Once prosthesis is built, gait analysis may help in comparing the wearer's
      performance with the new device and with the prior art, and in verification of
      the hypotheses being put forward during the development process. In this lecture,
      we will discuss some synergies of normal gait. We will focus on the required
      biomechanical properties of a prosthetic leg that can allow the prosthesis's
      inclusion in normal gait synergy without demanding excessive compensatory
      movements. We will consider contribution of leg joints to generation of
      propulsion for adequate design of lower limb prostheses especially those with
      power supply.

PMID- 23957209
TI  - Phosphorylation of Noxo1 at threonine 341 regulates its interaction with Noxa1
      and the superoxide-producing activity of Nox1.
AB  - Superoxide production by Nox1, a member of the Nox family NAPDH oxidases,
      requires expression of its regulatory soluble proteins Noxo1 (Nox organizer 1)
      and Noxa1 (Nox activator 1) and is markedly enhanced upon cell stimulation with
      phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C
      (PKC). The mechanism underlying PMA-induced enhancement of Nox1 activity,
      however, remains to be elucidated. Here we show that, in response to PMA, Noxo1
      undergoes phosphorylation at multiple sites, which is inhibited by the PKC
      inhibitor GF109203X. Among them, Thr341 in Noxo1 is directly phosphorylated by
      PKC in vitro, and alanine substitution for this residue reduces not only PMA
      induced Noxo1 phosphorylation but also PMA-dependent enhancement of Nox1
      catalyzed superoxide production. Phosphorylation of Thr341 allows Noxo1 to
      sufficiently interact with Noxa1, an interaction that participates in Nox1
      activation. Thus phosphorylation of Noxo1 at Thr341 appears to play a crucial
      role in PMA-elicited activation of Nox1, providing a molecular link between PKC
      mediated signal transduction and Nox1-catalyzed superoxide production.
      Furthermore, Ser154 in Noxo1 is phosphorylated in both resting and PMA-stimulated
      cells, and the phosphorylation probably participates in a PMA-independent
      constitutive activity of Nox1. Ser154 may also be involved in protein kinase A
      (PKA) mediated regulation of Nox1; this serine is the major residue that is
      phosphorylated by PKA in vitro. Thus phosphorylation of Noxo1 at Thr341 and at
      Ser154 appears to regulate Nox1 activity in different manners. STRUCTURED DIGITAL
      ABSTRACT: Noxo1 binds to p22phox by pull down (1, 2, 3) Noxo1 binds to Noxo1 by
      pull down (View interaction) Noxa1 binds to Noxo1 by pull down (1, 2, 3, 4, 5).

PMID- 23957210
TI  - Protein structural statistics with PSS.
AB  - Characterizing the variability within an ensemble of protein structures is a
      common requirement in structural biology and bioinformatics. With the increasing
      number of protein structures becoming available, there is a need for new tools
      capable of automating the structural comparison of large ensemble of structures.
      We present Protein Structural Statistics (PSS), a command-line program written in
      Perl for Unix-like environments, dedicated to the calculation of structural
      statistics for a set of proteins. PSS can perform multiple sequence alignments,
      structure superpositions, calculate Cartesian and dihedral coordinate statistics,
      and execute cluster analyses. An HTML report that contains a convenient summary
      of results with figures, tables, and hyperlinks can also be produced. PSS is a
      new tool providing an automated way to compare multiple structures. It integrates
      various types of structural analyses through an user-friendly and flexible
      interface, facilitating the access to powerful but more specialized programs. PSS
      is easy to modify and extend and is distributed under a free and open source
      license. The relevance of PSS is illustrated by examples of application to
      pertinent biological problems. 

PMID- 23957211
TI  - Synthesis and growth mechanism of thin-film TiO2 nanotube arrays on focused-ion
      beam micropatterned 3D isolated regions of titanium on silicon.
AB  - In this paper, the fabrication and growth mechanism of net-shaped micropatterned
      self-organized thin-film TiO2 nanotube (TFTN) arrays on a silicon substrate are
      reported. Electrochemical anodization is used to grow the nanotubes from thin
      film titanium sputtered on a silicon substrate with an average diameter of ~30 nm
      and a length of ~1.5 MUm using aqueous and organic-based types of electrolytes.
      The fabrication and growth mechanism of TFTN arrays from micropatterned three
      dimensional isolated islands of sputtered titanium on a silicon substrate is
      demonstrated for the first time using focused-ion-beam (FIB) technique. This work
      demonstrates the use of the FIB technique as a simple, high-resolution, and
      maskless method for high-aspect-ratio etching for the creation of isolated
      islands and shows great promise toward the use of the proposed approach for the
      development of metal oxide nanostructured devices and their integration with
      micro- and nanosystems within silicon-based integrated-circuit devices.

PMID- 23957212
TI  - Effect of substituents on the structure, stability, and pi-dimerization of
      dithienylpyrrole radical cations.
AB  - A series of 2,5-di(2-thienyl)-N-methylpyrrole derivatives 1a-1d with methylthio
      end-capping groups and electron-donating substituents at the 3-position of the
      thiophene rings was synthesized, and the effects of the substituents on the
      structure, stability, and pi-dimerization ability of the radical cation were
      investigated using UV-vis-NIR and electron spin resonance spectra and density
      functional theory (DFT) calculations. Among the electron-donating methyl,
      methoxy, and methylthio substituents, the methoxy derivative 1c gave the most
      stable radical cation, which persisted in dichloromethane at room temperature
      under nitrogen for several hours without any apparent decomposition. In addition,
      1c(*+) had the largest pi-dimerization enthalpy among 1a(*+)-1d(*+). DFT
      calculations with the M06-2X method revealed that methyl and methylthio
      derivatives 1b(*+) and 1d(*+) as well as 1c(*+) adopt a cis-cis conformation, in
      contrast to the trans-trans conformer of unsubstituted 1a(*+), while the pi
      dimers of all of these compounds were shown to have a cis-cis conformation. On
      the basis of further detailed analyses, the preformed cis-cis conformation and
      the weaker intramolecular and intermolecular steric repulsions were considered to
      explain why 1c(*+) has the largest pi-dimerization enthalpy. 

PMID- 23957213
TI  - 14q32 translocations and 13q14 deletions are common cytogenetic abnormalities in
      POEMS syndrome.
AB  - OBJECTIVE: POEMS syndrome is a paraneoplastic syndrome characterized by
      polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell (PC)
      proliferative disease, and skin changes. Although chromosomal aberrations have
      been found and extensively described for other PC disorders, whether POEMS
      syndrome shares similar cytogenetic profiles has been rarely reported. In this
      study, we aimed to clarify the cytogenetic abnormalities of patients with POEMS
      syndrome in our center. METHODS: Purified CD138(+) PCs from bone marrow samples
      of twenty patients with POEMS syndrome were studied by interphase fluorescence in
      situ hybridization (FISH). FISH results were analyzed for an association between
      cytogenetic changes and clinical features. RESULTS: A majority of patients (65%)
      were found to bear cytogenetic aberrations commonly seen in multiple myeloma. The
      14q32 (IGH) translocation was observed in 45% of the cases and included the
      t(4;14) and t(11;14) translocation (15% and 25% of the cases, respectively). In
      addition, 25% of the patients had deletions of 13q14 and 20% had an amplification
      of 1q21. No significant correlation between clinical features with cytogenetic
      abnormalities was observed, although patients with IGH translocations were more
      likely to exhibit papilledema (P = 0.018). CONCLUSION: Cytogenetic aberrations in
      POEMS syndrome were similar to other PC dyscrasias, but at different percentages.

PMID- 23957214
TI  - Applying the ICF to identify requirements for students with Asperger syndrome in
      higher education.
AB  - Higher education requires more than academic skills and everyday student-life can
      be stressful. Students with Asperger syndrome (AS) may need support to manage
      their education due to difficulties in social functioning. OBJECTIVE: As
      preparation for the development of a structured tool to guide student and
      coordinator dialogues at Swedish universities, this study aimed to identify ICF
      categories that reflect requirements in everyday student-life for students with
      AS. METHODS: Using descriptive qualitative approach, information in documents
      reflecting the perspectives of university students, international
      classifications, user/health organisations and education authorities were linked
      to ICF codes. RESULTS: In total, 114 ICF categories were identified, most of
      which related to learning, tasks and demands, communication and interactions.
      CONCLUSION: Students with AS need varying accommodations to be successful in
      higher education. In the future, ICF-based code sets, including demands on
      student roles, can be used as checklists to describe functioning and needs for
      support.

PMID- 23957215
TI  - Complexation facilitated reduction of aromatic N-oxides by aqueous Fe(II)-tiron
      complex: reaction kinetics and mechanisms.
AB  - Rapid reduction of carbadox (CDX), olaquindox and several other aromatic N-oxides
      were investigated in aqueous solution containing Fe(II) and tiron. Consistent
      with previous work, the 1:2 Fe(II)-tiron complex, FeL2(6-), is the dominant
      reactive species as its concentration linearly correlates with the observed rate
      constant kobs under various conditions. The N-oxides without any side chains were
      much less reactive, suggesting direct reduction of the N-oxides is slow. UV-vis
      spectra suggest FeL2(6-) likely forms 5- or 7-membered rings with CDX and
      olaquindox through the N and O atoms on the side chain. The formed inner-sphere
      complexes significantly facilitated electron transfer from FeL2(6-) to the N
      oxides. Reduction products of the N-oxides were identified by HPLC/QToF-MS to be
      the deoxygenated analogs. QSAR analysis indicated neither the first electron
      transfer nor N-O bond cleavage is the rate-limiting step. Calculations of the
      atomic spin densities of the anionic N-oxides confirmed the extensive
      delocalization between the aromatic ring and the side chain, suggesting complex
      formation can significantly affect the reduction kinetics. Our results suggest
      the complexation facilitated N-oxide reduction by Fe(II)-tiron involves a free
      radical mechanism, and the subsequent deoxygenation might also benefit from the
      weak complexation of Fe(II) with the N-oxide O atom. 

PMID- 23957216
TI  - Facile catch and release of fullerenes using a photoresponsive molecular tube.
AB  - A novel M2L2 molecular tube capable of binding fullerene C60 was synthesized from
      bispyridine ligands with embedded anthracene panels and Ag(I) hinges. Unlike
      previous molecular cages and capsules, this open-ended tubular host can
      accommodate a single molecule of various C60 derivatives with large substituents.
      The fullerene guest can then be released by using the ideal, noninvasive external
      stimulus, light. 

PMID- 23957217
TI  - Combined biomarkers evaluation for diagnosing kidney injury in preeclampsia.
AB  - OBJECTIVE: To identify novel potential biomarkers and evaluate combined
      biomarkers for diagnosing kidney injury with considerable accuracy in
      preeclampsia. METHODS: The level of serum and urine neutrophil gelatinase
      associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), retinol-binding
      protein (RBP) and interleukin-18 (IL-18) were measured by enzyme-linked
      immunosorbent assay. RESULTS: The level of serum cystatin C, urine RBP, urine
      NGAL and urine KIM-1 in preeclampsia group were higher than that in the normal
      pregnancy group. When four biomarkers are combined, the sensitivity and
      specificity are 100%/98.20%. CONCLUSION: Urine KIM-1 is the most potential
      biomarker for renal injury in preeclampsia. The more biomarkers combined, the
      more sensitivity and specificity were increased.

PMID- 23957218
TI  - Modulation of Abeta(1-40) peptide fibrillar architectures by Abeta-based peptide
      amphiphiles.
AB  - Modulation of the fibrillogenesis of amyloid peptide Abeta(1-40) with two Abeta
      based peptide amphiphiles has been studied. Both peptide amphiphiles contain two
      alkyl chains but in different positions. The two alkyl chains of 2C12-Abeta(11
      17) are attached to the same terminus of Abeta(11-17), while those of C12
      Abeta(11-17)-C12 are separately attached to opposite termini of Abeta(11-17).
      Thioflavin T fluorescence spectroscopy shows that all the peptide amphiphiles
      promote the formation of the cross-beta-sheet structure of Abeta(1-40) and the
      aggregation of Abeta(1-40), while 2C12-Abeta(11-17) does this more efficiently.
      The atom force microscopy images indicate that the modulations of these two
      peptide amphiphiles on the Abeta(1-40) aggregation experience two distinct
      pathways. 2C12-Abeta(11-17) leads to amorphous aggregates, whereas C12-Abeta(11
      17)-C12 generates short rodlike fibrils. However, Fourier transform infrared
      spectroscopy suggests that the amorphous aggregates and rodlike fibrils display
      similar secondary structures. This work suggests that the aggregation ability and
      the aggregate structures of the peptide amphiphiles significantly affect their
      interactions with Abeta(1-40) and lead to different morphologies of the Abeta(1
      40) aggregates. 

PMID- 23957220
TI  - Intracerebroventricular transplantation of ex vivo expanded endothelial colony
      forming cells restores blood-brain barrier integrity and promotes angiogenesis of
      mice with traumatic brain injury.
AB  - Endothelial progenitor cells (EPCs) play a key role in tissue repair and
      regeneration. Previous studies have shown a positive correlation between the
      number of circulating EPCs and clinical outcomes of patients with traumatic brain
      injury (TBI). A recent study has further shown that intravenous infusion of human
      umbilical cord blood-derived endothelial colony-forming cells (ECFCs) improves
      outcomes of mice subjected to experimental TBI. This follow-up study was designed
      to determine whether intracerebroventricular (i.c.v.) infusion of ECFCs, which
      may reduce systemic effects of these cells, could repair the blood-brain barrier
      (BBB) and promote angiogenesis of mice with TBI. Adult nude mice were exposed to
      fluid percussion injury and transplanted i.c.v. with ECFCs on day 1 post-TBI.
      These ECFCs were detected at the TBI zone 3 days after transplantation by SP
      DiIC18(3) and fluorescence in situ hybridization. Mice with ECFCs transplant had
      reduced Evans blue extravasation and brain water content, increased expression of
      ZO-1 and claudin-5, and showed a higher expression of angiopoietin 1. Consistent
      with the previous report, mice with ECFCs transplant had also increased
      microvascular density. Modified neurological severity score and Morris water maze
      test indicated significant improvements in motor ability, spatial acquisition and
      reference memory in mice receiving ECFCs, compared to those receiving saline.
      These data demonstrate the beneficial effects of ECFC transplant on BBB integrity
      and angiogenesis in mice with TBI.

PMID- 23957221
TI  - Evolving pharmacology of orphan GPCRs: IUPHAR Commentary.
AB  - The award of the 2012 Nobel Prize in Chemistry to Robert Lefkowitz and Brian
      Kobilka for their work on the structure and function of GPCRs, spanning a period
      of more than 20 years from the cloning of the human beta2 -adrenoceptor to
      determining the crystal structure of the same protein, has earned both
      researchers a much deserved place in the pantheon of major scientific
      discoveries. GPCRs comprise one of the largest families of proteins, controlling
      many major physiological processes and have been a major focus of the
      International Union of Basic and Clinical Pharmacology Committee on Receptor
      Nomenclature and Drug Classification (NC-IUPHAR) since its inception in 1987. We
      report here recent efforts by the British Pharmacological Society and NC-IUPHAR
      to define the endogenous ligands of 'orphan' GPCRs and to place authoritative and
      accessible information about these crucial therapeutic targets online. 

PMID- 23957222
TI  - The role of suppression in resolving interference: evidence for an age-related
      deficit.
AB  - Difficulty with memory retrieval is a salient feature of cognitive aging and may
      be related to a reduction in the ability to suppress items that compete for
      retrieval. To test this hypothesis directly, we presented a series of words for
      shallow coding that included pairs of orthographically similar words (e.g.,
      ALLERGY and ANALOGY). After a delay, participants solved word fragments (e.g., A
      _ L _ _ GY) that resembled both words in a pair but could only be completed by
      one. We measured the consequence of having successfully resolved competition by
      having participants read a list of words including the rejected competitors as
      quickly as possible. Response time was compared with control conditions that did
      not require resolving competition. Older adults showed no evidence of
      suppression; instead they showed priming for the competitors, in sharp contrast
      to strong suppression effects previously observed in younger adults. Whereas
      previous studies have provided clear evidence for suppression deficits by
      examining the ability to produce targets in high interference situations, here we
      provide direct evidence for a suppression deficit by examining the accessibility
      of rejected competitors.

PMID- 23957223
TI  - Social regulatory processes in later life: a web-based microlongitudinal study.
AB  - The goal for this study was to examine within-person processes driving individual
      development related to social goals. We examined how social regulatory processes
      travel together over time to understand whether daily social goal progress is
      sensitive to variation in experiences of support and hindrance and the extent to
      which maintenance or achievement goal orientation explains differences in
      sensitivity to social experiences. A sample of 105 adults over the age of 50
      years chose an individually meaningful social goal to track over time, which they
      coded as achievement or maintenance oriented. Participants then reported their
      daily progress and experiences of support and hindrance toward that goal over a
      100-day study period. We found social goal progress to positively covary with
      support and negatively covary with hindrance. These linkages, which we termed
      sensitivity, varied significantly across participants. This variation was
      partially explained by differences in goal orientation. Those with an achievement
      goal made lower goal progress and were more sensitive to support and less
      sensitive to hindrance than those with a maintenance-oriented goal. Our findings
      partially explain the processes by which older adults work toward their social
      goals. Daily goal progress is contingent on daily social experiences, but these
      sensitivities are in part shaped by goal orientation.

PMID- 23957224
TI  - Longitudinal mediation of processing speed on age-related change in memory and
      fluid intelligence.
AB  - Age-related decline in processing speed has long been considered a key driver of
      cognitive aging. While the majority of empirical evidence for the processing
      speed hypothesis has been obtained from analyses of between-person age
      differences, longitudinal studies provide a direct test of within-person change.
      Using recent developments in longitudinal mediation analysis, we examine the
      speed-mediation hypothesis at both the within-and between-person levels in two
      longitudinal studies, Longitudinal Aging Study Amsterdam (LASA) and Origins of
      Variance in the Oldest-Old (OCTO-Twin). We found significant within-person
      indirect effects of change in age, such that increasing age was related to lower
      speed, which in turn relates to lower performance across repeated measures on
      other cognitive outcomes. Although between-person indirect effects were also
      significant in LASA, they were not in OCTO-Twin which is not unexpected given the
      age homogeneous nature of the OCTO-Twin data. A more in-depth examination through
      measures of effect size suggests that, for the LASA study, the within-person
      indirect effects were small and between-person indirect effects were consistently
      larger. These differing magnitudes of direct and indirect effects across levels
      demonstrate the importance of separating between- and within-person effects in
      evaluating theoretical models of age-related change.

PMID- 23957225
TI  - Cognitive decline impairs financial and health literacy among community-based
      older persons without dementia.
AB  - Literacy is an important determinant of health and well-being across the life
      span but is critical in aging, when many influential health and financial
      decisions are made. Prior studies suggest that older persons exhibit lower
      literacy than younger persons, particularly in the domains of financial and
      health literacy, but the reasons why remain unknown. The objectives of this study
      were to: (a) examine pathways linking diverse resources (i.e., education, word
      knowledge, cognitive function, and decision making style) to health and financial
      literacy among older persons and determine the extent to which the relation of
      age with literacy represents a direct effect versus an indirect effect due to
      decrements in specific cognitive functions (i.e., executive functions and
      episodic memory); and (b) test the hypothesis that declines in executive function
      and episodic memory are associated with lower literacy among older persons
      without dementia. Six-hundred and forty-five community-based older persons
      without dementia underwent detailed assessments of diverse resources, including
      education, word knowledge, cognitive function (i.e., executive function, episodic
      memory) and decision making style (i.e., risk aversion), and completed a measure
      of literacy that included items similar to those used in the Health and
      Retirement Study, such as numeracy, financial concepts such as compound inflation
      and knowledge of stocks and bonds, and important health concepts such as
      understanding of drug risk and Medicare Part D. Path analysis revealed a strong
      effect of age on literacy, with about half of the effect of age on literacy due
      to decrements in executive functions and episodic memory. In addition, executive
      function had an indirect effect on literacy via decision making style (i.e., risk
      aversion), and education and word knowledge had independent effects on literacy.
      Finally, among (n = 447) persons with repeated cognitive assessments available
      for up to 14 years, regression analysis supported the association of multiple
      resources with literacy; moreover, more rapid declines in executive function and
      episodic memory over an average of 6.4 years prior to the literacy assessment
      predicted lower literacy scores (ps < 0.02), but rate of decline in word
      knowledge did not. These findings suggest that diverse individual resources
      contribute to financial and health literacy and lower literacy in old age is
      partially due to declines in executive function and episodic memory.

PMID- 23957226
TI  - Verbal working and long-term episodic memory associations with white matter
      microstructure in normal aging investigated using tract-based spatial statistics.
AB  - Reductions in the integrity of white matter microstructure are thought to be a
      significant cause of age-related decline in mnemonic abilities, including working
      memory (WM) and long-term episodic memory (LTM). This study uses tract-based
      spatial statistics (TBSS) applied to diffusion tensor magnetic resonance images
      to explore correlations between white matter microstructure and verbal WM and LTM
      in a sample of 98 normal older adults. WM performance was associated with
      microstructure in left fronto-parietal pathways and LTM was associated with
      bilateral fronto-temporal pathways. Interhemispheric-frontal pathways (genu of
      the corpus callosum) were associated with both types of mnemonic function. We
      hypothesize that in normal aging, damage to certain white matter pathways may
      reduce the dynamic efficiency of mnemonic abilities by disrupting the connections
      within multiple distributed networks. By correlating white matter with two
      mnemonic functions in the same analysis, we have demonstrated that regional white
      matter networks may share common mnemonic functions but also may be
      differentiated for memory types.

PMID- 23957219
TI  - A contrast between children and adolescents with excellent and poor control: the
      T1D Exchange clinic registry experience.
AB  - OBJECTIVES: Optimizing glycemic control in pediatric type 1 diabetes (T1D) is
      essential to minimizing long-term risk of complications. We used the T1D Exchange
      database from 58 US diabetes clinics to identify differences in diabetes
      management characteristics among children categorized as having excellent vs.
      poor glycemic control. METHODS: Among registry participants 6-17 yr old with
      diabetes duration >= 2 yr, those with excellent control [(A1c <7%)(53 mmol/mol)
      (N = 588)] were compared with those with poor control [(A1c >= 9% )(75 mmol/mol)
      (N = 2684)] using logistic regression. RESULTS: The excellent and poor control
      groups differed substantially in diabetes management (p < 0.001 for all) with
      more of the excellent control group using insulin pumps, performing blood glucose
      monitoring >= 5 */d, missing fewer boluses, bolusing before meals rather than at
      the time of or after a meal, using meal-specific insulin:carbohydrate ratios,
      checking their blood glucose prior to giving meal time insulin, giving insulin
      for daytime snacks, giving more bolus insulin, and using a lower mean total daily
      insulin dose than those in poor control. After adjusting for demographic and
      socioeconomic factors, diabetes management characteristics were still strongly
      associated with good vs. poor control. Notably, frequency of severe hypoglycemia
      was similar between the groups while DKA was more common in the poorly controlled
      group. CONCLUSIONS: Children with excellent glycemic control tend to exhibit
      markedly different diabetes self-management techniques than those with poor
      control. This knowledge may further inform diabetes care providers and patients
      about specific characteristics and behaviors that can be augmented to potentially
      improve glycemic control.

PMID- 23957227
TI  - When feeling different pays off: how older adults can counteract negative age
      related information.
AB  - Negative age stereotypes are pervasive and threaten older adults' self-esteem.
      Two experiments tested the hypothesis that differentiation from one's age group
      reduces the impact of negative age-related information on older adults' self
      evaluation. In Experiment 1, older adults (N = 83, M = 71.9 years) were
      confronted with neutral or negative age-related information followed by a
      manipulation of self-differentiation. Experiment 2 (N = 44, M = 73.55 years)
      tested the moderating role of self-differentiation in the relationship of
      implicit attitudes toward older adults and implicit self-esteem. Results suggest
      that self-differentiation prevents the impact of negative age-related information
      on older adults' self-esteem.

PMID- 23957228
TI  - Visit complexity, diagnostic uncertainty, and antibiotic prescribing for acute
      cough in primary care: a retrospective study.
AB  - BACKGROUND: Guidelines and performance measures recommend avoiding antibiotics
      for acute cough/acute bronchitis and presume visits are straightforward with
      simple diagnostic decision-making. We evaluated clinician-assigned diagnoses,
      diagnostic uncertainty, and antibiotic prescribing for acute cough visits in
      primary care. METHODS: We conducted a retrospective analysis of acute cough
      visits - cough lasting <=21 days in adults 18-64 years old without chronic lung
      disease - in a primary care practice from March 2011 through June 2012. RESULTS:
      Of 56,301 visits, 962 (2%) were for acute cough. Clinicians diagnosed patients
      with 1, 2, or >= 3 cough-related diagnoses in 54%, 35%, and 11% of visits,
      respectively. The most common principal diagnoses were upper respiratory
      infection (46%), sinusitis (10%), acute bronchitis (9%), and pneumonia (8%).
      Clinicians prescribed antibiotics in 22% of all visits: 65% of visits with
      antibiotic-appropriate diagnoses and 4% of visits with non-antibiotic-appropriate
      diagnoses. Clinicians expressed diagnostic uncertainty in 16% of all visits: 43%
      of visits with antibiotic-appropriate diagnoses and 5% of visits with non
      antibiotic-appropriate diagnoses. Clinicians expressed uncertainty more often
      when prescribing antibiotics than when not prescribing antibiotics (30% vs. 12%;
      p < 0.001). As the number of visit diagnoses increased from 1 to 2 to >= 3,
      clinicians were more likely to express diagnostic uncertainty (5%, 25%, 40%,
      respectively; p < 0.001) and prescribe antibiotics (16%, 25%, 41%, respectively;
      p < 0.001). CONCLUSIONS: Acute cough may be more complex and have more diagnostic
      uncertainty than guidelines and performance measures presume. Efforts to reduce
      antibiotic prescribing for acute cough should address diagnostic complexity and
      uncertainty that clinicians face.

PMID- 23957229
TI  - FK506-binding protein 12 ligands: a patent review.
AB  - INTRODUCTION: FK506-binding protein 12 (FKBP12) is an endogenous protein with
      peptidyl-prolyl isomerase (PPIase) activity. Natural compounds FK506, rapamycin
      and ascomycin, are FKBP12 ligands used for treating organ transplant rejection
      and other diseases. Small ligands that also interact with FKBP12 are designed and
      synthetized based on the natural ligands. This suggests that targeting FKBP12 has
      potential in the treatment of multiple diseases. AREAS COVERED: This article
      describes the features of FKBP12 and the therapeutic actions of agents targeting
      FKBP12 reported in the published articles and patents. EXPERT OPINION: The
      multiple functions of FKBP12 cause side effects during therapy with FKBP12
      ligands. The interaction between FKBP12 and other receptors should be explored to
      guide their use as drugs in the clinical setting. In addition, the
      neuroprotective mechanism of small-molecule FKBP12 ligands needs further study in
      order to develop them as novel drugs for treating neurological disorders.

PMID- 23957230
TI  - Response to Dr. Sarlak et al.: letter to the editor 'A larger weight reduction is
      necessary to elicit an increase in adiponectin and a decrease in leptin levels'.

PMID- 23957231
TI  - Bioefficacy of hydromethanolic extract of tuber of Chlorophytum borivilianum
      (Safed Musli) for the management of male infertility in cyproterone acetate
      treated albino rats.
AB  - Increase in male sexual dysfunction, and its treatment with conventional
      aphrodisiac drugs with side effects lead to investigate the spermatogenesis and
      androgenesis augmentative efficacy of hydromethanolic (40 : 60) extract of root
      of Chlorophytum borivilianum (family - Liliaceae) against cyproterone acetate
      induced subfertility in Wistar strain male albino rat. For this purpose,
      experimental rats were divided into three treatment groups: vehicle (received
      distilled water), cyproterone acetate (gastric intubation at 250 mg kg(-1) twice
      daily for 35 days) and cyproterone acetate plus root extract of C. borivilianum
      (gastric intubation at 250 mg kg(-1) plus 400 mg kg(-1) with an interval of 20
      min twice daily for 35 days). After 35-day treatment, all rats were euthanised.
      Reproductive deviations towards negative side were investigated by screening the
      spermatogenic and steroidogenic biosensors. Oxidative stress profile in
      reproductive organs and sperm pellet was evaluated by biochemical assessment of
      antioxidative enzyme activities and level of end products of the lipid
      peroxidation. Apoptosis profile was evaluated by Western blot study, TUNEL assay
      and DNA fragmentation study of testicular tissues. Evaluation of toxicity profile
      was included for experimental investigation. After cyproterone acetate treatment,
      the pituitary-testicular axis was deviated towards the negative side and its
      tuning system was affected by oxidative stress and apoptosis-mediated process,
      which reduced the quality of semen and finally led to subfertility. Co
      administration of C. borivilianum root extract enhanced male reproductive
      potentiality and prevented the negative deviations after the treatment with
      cyproterone acetate by means of increasing oxidative defence and maintaining
      homeostasis in testicular apoptosis process.

PMID- 23957232
TI  - Analysis of wear of polyethylene hip joint cup related to its positioning in
      patient's body.
AB  - Polyethylene parts of endoprosthesis are the weakest parts of each medical
      implant. They can be worn out within several years. During this period, a patient
      can enjoy good physical efficiency until the wear of polyethylene part limits
      his/her mobility. Then the reoperation is necessary and positioning of all parts
      of endoprosthesis has an effect on future patient's mobility and durability of
      implant. Elements of endoprosthesis during exploitation are heavily loaded both
      by normal and tangential forces and moments. In this paper, the dependence of
      wear of polyethylene cup on its positioning in pelvis is the major problem. Wear
      of the cup is determined by two measures: the depth and volume of a material
      rubbed off from the contact surface. The sensitivity of the depth of rubbing off
      is evaluated relative to two angles of anteversion and abduction, and radii of
      the cup. Numerical results are obtained by using Abaqus FE system with data
      related to patient's activity identified on the basis of medical reports.

PMID- 23957234
TI  - Dialectics of gender and health: the case of HIV serodiscordance.
AB  - The relationship between gender and health is a deeply interdependent one. Yet
      research in this area has focused primarily on how gender relations determine
      health behaviour and health outcomes. This article advocates a more holistic
      approach that conceptualises gender and health as fully intertwined and mutually
      constitutive. This interplay is explored through the case of HIV serodiscordance
      in which one person in a relationship is HIV positive and the other HIV negative.
      Drawing on in-depth research with discordant couples in urban Uganda, this study
      indicates that living with discordance can both reinforce and challenge normative
      gender power dynamics in relationships. This study, therefore, illustrates how
      significant health problems can influence gender relations. As such, it reveals
      the dialectical relationship between gender and health and also provides
      important insights for HIV prevention in the new era of antiretroviral treatment
      as prevention. 

PMID- 23957236
TI  - A case of depressive personality disorder: aligning theory, practice, and
      clinical research.
AB  - Depressive personality disorder (DPD) is highly studied and common in clinical
      settings. Nevertheless, it is rife with controversies and often overshadowed by
      major depression and dysthymia with which it shares many similarities but also is
      clinically distinct. Possibly as a result, DPD is underdiagnosed and
      misunderstood in clinical care. Thus the goal of this practice review is to
      present a case from psychiatric clinical work illustrating how DPD may be
      commonly overlooked in routine care, and how the conceptualization of this case
      and its treatment plan changed course once DPD was considered by treating staff,
      ultimately contributing to the successful outcome of the case. Questions elicited
      by the case are subsequently discussed in the context of the empirical literature
      on DPD, allowing for a clearer picture to emerge on DPD and its role in the
      development, course, and treatment of depression.

PMID- 23957235
TI  - High prevalence of thyroid dysfunction among pregnant women in Lubumbashi,
      Democratic Republic of Congo.
AB  - BACKGROUND: Despite notable progress in the fight against iodine deficiency
      disorders in the Democratic Republic of Congo, a recent study has shown that
      pregnant women in Lubumbashi were still iodine deficient. Our objective was to
      assess thyroid function in this population. METHODS: In a cross-sectional study
      conducted in maternity units from three different socioeconomic areas in
      Lubumbashi, serum thyrotropin, free thyroxine, thyroglobulin, and thyroperoxidase
      antibodies were measured in 225 pregnant women attending antenatal visits, in 75
      women who recently delivered, and in 75 nonpregnant controls. The outcome was the
      prevalence of thyroid dysfunction. RESULTS: Median values in pregnant women,
      women who recently delivered, and nonpregnant women were 1.80, 2.80, and 1.54
      mIU/L for thyrotropin (p<0.001); 0.85, 1.11, and 1.16 ng/dL for free thyroxine
      (p<0.001); and 13.3, 9.5, and 10.4 ng/mL for thyroglobulin (p=0.01),
      respectively. The prevalence of thyroid dysfunction in pregnant women, in women
      who recently delivered, and in nonpregnant women was 31%, 8%, and 20% for
      isolated hypothyroxinemia (p<0.001); 12%, 24%, and 5% for subclinical
      hypothyroidism (p=0.002); 8%, 3%, and 3%, for overt hypothyroidism (p=0.09); and
      5%, 13%, and 4%, for positive thyroperoxidase antibodies (p=0.03), respectively.
      In multiple logistic regression, women who were pregnant or who recently
      delivered, who lived in a poor socioeconomic area, and who had low urinary iodine
      concentration were more likely to have an increased serum thyrotropin: odds ratio
      (OR)=3.43 (95% confidence interval [CI] 1.23-9.53) for pregnancy, OR=4.49 [CI
      1.66-15.01] for postpartum period, OR=3.68 [CI 1.85-7.35] for semiurban area, and
      OR=0.44 [CI 0.19-0.96] for urinary iodine concentration >= 250 MUg/L.
      CONCLUSIONS: Our results show that there is a high prevalence of thyroid
      dysfunction in pregnant women of Lubumbashi, and this high prevalence is
      associated with iodine deficiency. To prevent obstetrical adverse outcomes and
      neurological damage in children, iodine supplementation is needed before
      conception or in early pregnancy in Lubumbashi.

PMID- 23957237
TI  - Corrosion behaviour of polished and sandblasted titanium alloys in PBS solution.
AB  - In this work, we performed comparative studies of the effect of surface
      preparation of Ti6Al4V and Ti6Al7Nb biomedical alloys and the influence of
      endothelial cells on their corrosion behaviour in PBS (Phosphate Buffered
      Saline). Two different methods of surface modification were applied - polishing
      and sandblasting. The polished Ti6Al7Nb alloy was found to have the best
      resistance against general corrosion in PBS. It was characterized by the lowest
      corrosion rate, the widest passive range and the lowest reactivity. Both alloys
      prepared by sandblasting exhibited worse corrosion properties in comparison to
      the polished ones. This can be associated with a greater development of their
      surface and the presence of Al2O3 grains which caused an increase of corrosion
      potential but might also influence the weakening of the passive layer. Results of
      potentiodynamic anodic polarization indicated that more resistant to pitting
      corrosion was Ti6Al7Nb alloy regardless of the method of surface preparation. In
      those cases, anodic polarization caused only an increase of passive layer, while
      in the case of sandblasted Ti6Al4V alloy it caused a pitting corrosion. The
      results obtained allowed us to conclude that the niobium-titanium alloys had
      higher corrosion resistance than titanium alloys with vanadium. Moreover, it was
      stated that endothelial cells improved the corrosion resistance of all the
      titanium alloys examined.

PMID- 23957238
TI  - A review of intracoronary abciximab in percutaneous coronary interventions--where
      are we now and where do we go from here?
AB  - The rationale for intracoronary administration of abciximab is discussed. The
      data on use of intracoronary abciximab in percutaneous coronary interventions in
      acute coronary syndromes and STEMI are reviewed. Evaluation of the niche where
      intracoronary administration of abciximab may be useful and future research into
      the subject and relevant patents are discussed. 

PMID- 23957239
TI  - Adiponectin and lipoprotein metabolism.
AB  - Adiponectin is secreted by the adipose tissue and it has been shown to be down
      regulated in states of insulin resistance and in cardiovascular disease. It has
      also been found to be correlated with various parameters of lipoprotein
      metabolism, and in particular, it is associated with the metabolism of high
      density lipoprotein (HDL) and triglycerides; adiponectin appears to induce an
      increase in serum HDL, and conversely, HDL can up-regulate adiponectin levels,
      and in addition, adiponectin lowers serum triglycerides through enhancement of
      the catabolism of triglyceride-rich lipoproteins. Studies investigating whether
      adiponectin is causally linked with lipoprotein metabolism have yielded
      conflicting data, and the mechanisms underlying the interplay between adiponectin
      and lipoproteins remain to be elucidated. The adiponectin-HDL relationship can
      explain at least in part the presumed protective role of adiponectin in
      cardiovascular disease and the adiponectin changes observed after dieting,
      exercise and lipid-lowering treatment. Statins, fibrates, niacin and n-3 fatty
      acids may influence circulating adiponectin levels, indicating that adiponectin
      may mediate some of the metabolic effects of these agents. Further studies to
      investigate more thoroughly the role of adiponectin in lipoprotein metabolism in
      the human setting should be carefully planned, focusing on causality and the
      possible impact of adiponectin on the pathogenesis of cardiovascular disease. 

PMID- 23957240
TI  - The use of levoglucosan and radiocarbon for source apportionment of PM(2.5)
      carbonaceous aerosols at a background site in East China.
AB  - Samples of fine particulate matter (PM2.5) were collected during July 2009 to
      March 2010 at a regional background site in East China. The mass concentrations
      of organic carbon (OC) and elemental carbon (EC) were characterized by the
      highest levels in winter (December to February) and the lowest abundances in
      summer (June to August). Conversely, the concentrations of levoglucosan were
      higher in summer than in winter. The observations were associated to the
      anthropogenic air pollutions (predominantly fossil-fuel combustions) transport
      from the center and north China with the northwest winds in winter and large
      contribution of the open biomass burning activities in South China and East China
      in summer, which was evident by air-mass trajectories and MODIS satellite fire
      counts. To assign fossil and nonfossil contributions of carbonaceous matters, the
      radiocarbon contents in water-insoluble OC (WINSOC) and EC in 4 combined samples
      representing four seasons were analyzed using the isolation system established in
      China. The results indicated that biomass burning and biogenic sources (59%) were
      the major contribution to the WINSOC, whereas fossil fuel (78%) was the dominant
      contributor to the refractory EC at this site. The source variation obtained by
      radiocarbon was consistent with other indicators, such as the OC/EC ratios and
      the levoglucosan concentration. Biomass burning and biogenic emissions were found
      to predominate in the summer and autumn, whereas fossil fuel emissions
      predominate in winter and spring. 

PMID- 23957241
TI  - The endothelin axis in head and neck cancer: a promising therapeutic opportunity?
AB  - The incidence of head and neck cancer, predominantly consisting of squamous cell
      carcinomas (HNSCCs), is continuing to rise worldwide. Invasive HNSCC carries a
      poor prognosis, and the detrimental sequelae of surgical resection motivate
      identification of novel modes of therapeutic intervention. The endothelin (ET)
      axis consists of ET-1, 2 and 3, which are generated by endothelin-converting
      enzyme (ECE) and engage with the receptors ETA R and ETB R. The ET axis plays a
      role in the development and progression of various human malignancies. ET axis
      components have been found to be overexpressed in HNSCC; ET-1 antagonism and
      inhibition of ECE may therefore represent viable therapeutic opportunities. ET-1
      can promote HNSCC progression via stromal-epithelial interactions, suggesting
      that the stroma may also hold potential for therapies targeting components of the
      ET axis. The ET axis may also offer components that can be used as biomarkers -
      for screening, diagnosis, monitoring disease recurrence and prognostic risk
      stratification of patients - and targets for localised analgesia offering less
      systemic side effects. This review summarises the current knowledge and potential
      for clinical opportunities related to the ET axis. 

PMID- 23957242
TI  - Men managing cancer: a gender analysis.
AB  - As researchers consider gendered patterns in men's prostate cancer experiences,
      little attention has been devoted to how men manage 'cancer', more generally.
      Drawing on the experiences of 30 Canadian men with a variety of cancer types,
      this article details how men engaged illness self-management and help-seeking
      activities with lay and professional support persons. Results indicate three
      broad responsive strategies: fortifying resources, maintaining the familiar, and
      getting through. In these pursuits, the participants drew on a variety of
      performances to respond to social contexts demanding that men embody masculine
      ideals including strength, control, and stoicism. Considering gendered dynamics
      in how men manage the challenges of cancer, this article broadens understandings
      about men's cancer experiences by highlighting the drivers orienting
      participants' responsive efforts and challenging assumptions of help-seeking as
      essentially problematic for men in Western society. 

PMID- 23957243
TI  - Measuring decentering in self-reports: Psychometric properties of the experiences
      questionnaire in a German sample.
AB  - Decentering is described as referring to one's current mental experiences from an
      objective perspective. This study presents a psychometric evaluation of a German
      version of the Experiences Questionnaire (EQ-D), a self-report instrument
      designed to measure decentering. Confirmatory factor analysis on a sample of 506
      university students indicates acceptable-to-good model fit (chi(2)=58.3; TLI=.92;
      CFI=.95; RMSEA=.067) for a second-order factor Overall Decentering comprising the
      two first-order factors Accepting Self-Perception and Distanced Perspective.
      Preliminary evidence for the validity of the EQ-D was demonstrated via negative
      correlations with measures of depression and depressive rumination. The present
      results stress the multidimensional nature of decentering and provide important
      suggestions for future research on how to investigate and operationalize the
      decentering construct.

PMID- 23957244
TI  - Differences in gas exchange contribute to habitat differentiation in Iberian
      columbines from contrasting light and water environments.
AB  - During photosynthesis, respiration and transpiration, gas exchange occurs via the
      stomata and so plants face a trade-off between maximising photosynthesis while
      minimising transpiration (expressed as water use efficiency, WUE). The ability to
      cope with this trade-off and regulate photosynthetic rate and stomatal
      conductance may be related to niche differentiation between closely related
      species. The present study explored this as a possible mechanism for habitat
      differentiation in Iberian columbines. The roles of irradiance and water stress
      were assessed to determine niche differentiation among Iberian columbines via
      distinct gas exchange processes. Photosynthesis-irradiance curves (P-I curves)
      were obtained for four taxa, and common garden experiments were conducted to
      examine plant responses to water and irradiance stress, by measuring
      instantaneous gas exchange and plant performance. Gas exchange was also measured
      in ten individuals using two to four field populations per taxon. The taxa had
      different P-I curves and gas exchange in the field. At the species level, water
      stress and irradiance explained habitat differentiation. Within each species, a
      combination of irradiance and water stress explained the between-subspecies
      habitat differentiation. Despite differences in stomatal conductance and CO2
      assimilation, taxa did not have different WUE under field conditions, which
      suggests that the environment equally modifies photosynthesis and transpiration.
      The P-I curves, gas exchange in the field and plant responses to experimental
      water and irradiance stresses support the hypothesis that habitat differentiation
      is associated with differences among taxa in tolerance to abiotic stress mediated
      by distinct gas exchange responses. 

PMID- 23957245
TI  - Modular enantioselective synthesis of 8-aza-prostaglandin E1.
AB  - We report herein for the first time the enantioselective synthesis of 8-aza-PGE1.
      The synthesis used the cross olefin metathesis reaction to connect the 5-vinyl
      gamma-lactam subunit, prepared from (R)-malic acid via the Ley's sulfone-based
      alpha-amidalkylation protocol (dr = 6.8:1), with the chiral pre-omega-chain. The
      latter was synthesized in high enantioselectivity from (E)-2-octenol by the
      Sharpless asymmetric epoxidation and the titanocene-mediated epoxide opening.
      This modular approach is quite concise and flexible, and requires only eight
      steps from commercially available reagents. 

PMID- 23957246
TI  - Novel small molecule epithelial sodium channel inhibitors as potential
      therapeutics in cystic fibrosis - a patent evaluation.
AB  - Novel molecular platforms for epithelial sodium channel (ENaC) modulators are
      claimed in the following six patents: WO2012035158(A1); WO2009074575(A2);
      WO2011028740(A1); WO2009150137(A2); WO2011079087(A1); WO2008135557(A1). These
      ENaC inhibitors may be used in blocking transepithelial sodium and consequently
      water absorption across airway epithelia. This may result in airway rehydration
      and enhanced mucociliary clearance in patients with cystic fibrosis (CF) lung
      disease. All inhibitors resemble the classical ENaC blocker amiloride but follow
      different strategies to increase structural diversity in a sterically tolerant
      region. These substitutions can be modified to i) enhance potency of ENaC
      inhibition; ii) reduce epithelial permeability; and iii) broaden applicability in
      order to be used as potential drugs for CF therapy. Most of the claims and patent
      data are supported by the currently available literature. The patents deliver a
      solid chemical basis for a variety of chemical modifications of the ENaC
      inhibitor amiloride. These modifications may result in the development of a
      novel, applicable ENaC inhibitors which may have lasting effects on diseased
      airways and may achieve airway rehydration and enhanced mucociliary clearance in
      CF lung disease. 

PMID- 23957247
TI  - Poly(D-glucose carbonate) block copolymers: a platform for natural product-based
      nanomaterials with Solvothermatic characteristics.
AB  - A natural product-based polymer platform, having the characteristics of being
      derived from renewable materials and capable of breaking down, ultimately, into
      natural byproducts, has been prepared through the ring-opening polymerization
      (ROP) of a glucose-based bicyclic carbonate monomer. ROP was carried out via
      chain extension of a polyphosphoester (PPE) macroinitiator in the presence of
      1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) organocatalyst to afford the PPE-b
      poly(D-glucose carbonate) (PDGC) block copolymer. This new copolymer represents a
      functional architecture that can be rapidly transformed through thiol-yne
      reactions along the PPE segment into a diverse variety of amphiphilic polymers,
      which interestingly display stimuli-sensitive phase behavior in the form of a
      lower critical solution temperature (LCST). Below the LCST, they undergo self
      assembly to form spherical core-shell nanostructures that display a poorly
      defined core-shell morphology. It is expected that hydrophobic patches are
      exposed within the micellar corona, reminiscent of the surface complexity of
      proteins, making these materials of interest for triggered and reversible
      assembly disassembly processes.

PMID- 23957248
TI  - Modified colloidal primitive model as a homogeneous surface charge distribution:
      zeta-potential.
AB  - An integral equations theory is derived and applied to a modified colloidal
      primitive model (MCPM), for finite concentration colloidal dispersions. In MCPM,
      the charge on the colloidal particle is assumed to be smeared on its surface. We
      find important quantitative and qualitative differences of the zeta-potential,
      induced charge, and the colloid-colloid electric effective force, calculated in
      the MCPM, with those obtained from the colloidal primitive model (CPM), where the
      colloidal charge is assumed to be in the center of the particle, in spite of the
      fact that, due to Gauss's law, both models have the same particle distribution
      function. In particular, for the same parameters, while the zeta-potential is
      positive in MCPM, is negative in the CPM, implying opposite electrophoretic
      mobilities, MU. An inverse MU has been theoretically predicted in the past, for
      infinite dilution colloidal dispersions. The MCPM could be a better model for
      some colloidal particles. In both models, the CPM and the MCPM, it is found a
      very long-range colloid-colloid correlation, in accordance with previous Monte
      Carlo simulations. The electrostatic, as well as entropic, like-charged colloid
      colloid forces are oscillatory, implying a long-range attraction. 

PMID- 23957249
TI  - Associations between child temperament, maternal feeding practices and child body
      mass index during the preschool years: a systematic review of the literature.
AB  - It is a research priority to identify modifiable risk factors to improve the
      effectiveness of childhood obesity prevention strategies. Research, however, has
      largely overlooked the role of child temperament and personality implicated in
      obesogenic risk factors such as maternal feeding and body mass index (BMI) of
      preschoolers. A systematic review of relevant literature was conducted to
      investigate the associations between child temperament, child personality,
      maternal feeding and BMI and/or weight gain in infants and preschoolers; 18
      papers were included in the review. The findings revealed an association between
      the temperament traits of poor self-regulation, distress to limitations, low and
      high soothability, low negative affectivity and higher BMI in infants and
      preschool-aged children. Temperament traits difficult, distress to limitations,
      surgency/extraversion and emotionality were significantly associated with weight
      gain rates in infants. The results also suggested that child temperament was
      associated with maternal feeding behaviours that have been shown to influence
      childhood overweight and obesity, such as using restrictive feeding practices
      with children perceived as having poor self-regulation and feeding potentially
      obesogenic food and drinks to infants who are more externalizing. Interestingly,
      no studies to date have evaluated the association between child personality and
      BMI/weight gain in infants and preschoolers. There is a clear need for further
      research into the association of child temperament and obesogenic risk factors in
      preschool-aged children. 

PMID- 23957250
TI  - Single lipid vesicle assay for characterizing single-enzyme kinetics of
      phospholipid hydrolysis in a complex biological fluid.
AB  - Imaging of individual lipid vesicles is used to track single-enzyme kinetics of
      phospholipid hydrolysis. The method is employed to quantify the catalytic
      activity of phospholipase A2 (PLA2) in both pure and complex biological fluids.
      The measurements are demonstrated to offer a subpicomolar limit of detection
      (LOD) of human secretory PLA2 (sPLA2) in up to 1000-fold-diluted cerebrospinal
      fluid (CSF). An additional new feature provided by the single-enzyme sensitivity
      is that information about both relative concentration variations of active sPLA2
      in CSF and the specific enzymatic activity can be simultaneously obtained. When
      CSF samples from healthy controls and individuals diagnosed with Alzheimer's
      disease (AD) are analyzed, the specific enzymatic activity is found to be
      preserved within 7% in the different CSF samples whereas the enzyme concentration
      differs by up to 56%. This suggests that the previously reported difference in
      PLA2 activity in CSF samples from healthy and AD individuals originates from
      differences in the PLA2 expression level rather than from the enzyme activity.
      Conventional ensemble averaging methods used to probe sPLA2 activity do not allow
      one to obtain such information. Together with an improvement in the LOD of at
      least 1 order of magnitude compared to that of conventional assays, this suggests
      that the method will become useful in furthering our understanding of the role of
      PLA2 in health and disease and in detecting the pharmacodynamic effects of PLA2
      targeting drug candidates. 

PMID- 23957251
TI  - From determinants of RUNX1/ETO tetramerization to small-molecule protein-protein
      interaction inhibitors targeting acute myeloid leukemia.
AB  - We identified the first small-molecule protein-protein interaction inhibitors of
      RUNX1/ETO tetramerization applying structure-based virtual screening guided by
      predicted hot spots and pockets in the interface. A 3D similarity screening
      revealed specific hot spot mimetics, one of which prevents the proliferation of
      RUNX1/ETO-dependent SKNO-1 cells at low micromolar concentration. Using solely a
      protein-protein complex structure to start with, this strategy can be the first
      step in any comparable structure-based endeavor to identify protein-protein
      interaction inhibitors. 

PMID- 23957252
TI  - Prostate-specific targeting of the aqueous root extract of Croton membranaceus in
      experimental animals.
AB  - Croton membranaceus Mull.Arg. (Euphorbiaceae) is used for benign prostate
      hyperplasia (BPH) treatment. The study aimed at investigating organs that the
      aqueous root extracts of C. membranaceus (CMARE) target, which is absent in
      literature. Twenty-four male Sprague-Dawley rats (100-140 g) were randomly
      divided into 4 groups. Group 1, the control group received distilled water.
      Groups 2, 3 and 4 received 30, 150 and 300 mg kg(-1) b.wt CMARE respectively
      (oral gavage). Rats fed 90 days the standard chow diet ad libitum. Upon
      sacrifice, major organs were histologically examined and serum prostate-specific
      antigen (PSA) biochemically determined. Only the prostate was abnormal.
      Histologically, H&E staining revealed thickness and infoldings of the epithelial
      cells shrinking with increasing dose. The 30 mg kg(-1) group showed low columnar
      or flattened epithelium cells, whereas the columnar epithelium infoldings of the
      150 mg kg(-1) b.wt and 300 mg kg(-1) b.wt groups were virtually nonexistent. The
      acini of the control, 30 mg kg(-1) b.wt group and the 150 mg kg(-1) b.wt groups
      showed clear pinkish secretion. However, secretion of the high-dose group
      appeared light pink in colour and the stroma cells appeared much darker than all
      the treated and control group. C. membranaceus targets the prostate with
      significant PSA reduction (P < 0.01).

PMID- 23957254
TI  - Degenerative changes of the corticospinal tract in pediatric patients showing
      deteriorated motor function: A diffusion tensor tractography study.
AB  - OBJECTIVE: We attempted to demonstrate the corresponding degenerative changes of
      the affected corticospinal tract (CST) in pediatric patients with deteriorated
      motor function using diffusion tensor tractography (DTT). METHODS: We recruited
      three pediatric patients (corrected age: 2, 6 and 47 months, respectively) who
      showed impaired motor function. RESULTS: DTT in each patient showed interruption
      of the CSTs of the hemisphere contralateral to the side of motor impairment.
      Despite motor impairment and abnormal DTT findings, none of the three patients
      received rehabilitative therapy. The patients (corrected age: 9, 53 and 59
      months, respectively) and their parents visited our clinic again due to
      deterioration of motor functions. Follow-up DTT of all evaluated patients showed
      significant degenerative changes in the affected CSTs in accordance with the
      aggravation of motor impairment. CONCLUSION: We presented degenerative changes of
      the affected CSTs in pediatric patients according to the deterioration of motor
      function.

PMID- 23957253
TI  - The orthosteric GABAA receptor ligand Thio-4-PIOL displays distinctly different
      functional properties at synaptic and extrasynaptic receptors.
AB  - BACKGROUND AND PURPOSE: Explorations into the heterogeneous population of native
      GABA type A receptors (GABAA Rs) and the physiological functions governed by the
      multiple GABAA R subtypes have for decades been hampered by the lack of subtype
      selective ligands. EXPERIMENTAL APPROACH: The functional properties of the
      orthosteric GABAA receptor ligand 5-(4-piperidyl)-3-isothiazolol (Thio-4-PIOL)
      have been investigated in vitro, ex vivo and in vivo. KEY RESULTS: Thio-4-PIOL
      displayed substantial partial agonist activity at the human extrasynaptic GABAA R
      subtypes expressed in Xenopus oocytes, eliciting maximal responses of up to ~30%
      of that of GABA at alpha5 beta3 gamma2S , alpha4 beta3 delta and alpha6 beta3
      delta and somewhat lower efficacies at the corresponding alpha5 beta2 gamma2S ,
      alpha4 beta2 delta and alpha6 beta2 delta subtypes (maximal responses of 4-12%).
      In contrast, it was an extremely low efficacious agonist at the alpha1 beta3
      gamma2S , alpha1 beta2 gamma2S , alpha2 beta2 gamma2S , alpha2 beta3 gamma2S ,
      alpha3 beta2 gamma2S and alpha3 beta3 gamma2S GABAA Rs (maximal responses of 0
      4%). In concordance with its agonism at extrasynaptic GABAA Rs and its de facto
      antagonism at the synaptic receptors, Thio-4-PIOL elicited robust tonic currents
      in electrophysiological recordings on slices from rat CA1 hippocampus and
      ventrobasal thalamus and antagonized phasic currents in hippocampal neurons.
      Finally, the observed effects of Thio-4-PIOL in rat tests of anxiety, locomotion,
      nociception and spatial memory were overall in good agreement with its in vitro
      and ex vivo properties. CONCLUSION AND IMPLICATIONS: The diverse signalling
      characteristics of Thio-4-PIOL at GABAA Rs represent one of the few examples of a
      functionally subtype-selective orthosteric GABAA R ligand reported to date. We
      propose that Thio-4-PIOL could be a useful pharmacological tool in future studies
      exploring the physiological roles of native synaptic and extrasynaptic GABAA Rs.

PMID- 23957255
TI  - Effect on anxiety and depression of a multifactorial risk factor intervention
      program after stroke and TIA: a randomized controlled trial.
AB  - OBJECTIVES: Depression and anxiety related to stroke are caused by vascular
      lesions and psychological reactions. Treatment of vascular and modifiable
      behavioral risk factors reduces the risk of stroke and may also reduce the risk
      of emotional changes after stroke. We aimed to investigate whether a
      multifactorial risk factor intervention program in patients with first-ever
      stroke or transient ischemic attack (TIA) can influence post-stroke anxiety and
      depressive symptoms in patients one year post-stroke. METHOD: The study
      population consisted of first-ever stroke and TIA patients allocated in a
      randomized, evaluator-blinded, controlled trial to care as usual or a structured
      and multidisciplinary follow-up including intensive treatment of vascular risk.
      The primary endpoint (cognition) has previously been reported. The secondary
      endpoint, reported here, was changes in the Hospital Anxiety and Depression Scale
      (HADS) from baseline to 12-month follow-up. RESULTS: One hundred and ninety-five
      patients were randomized. The estimated difference between treatment groups, in
      changes in HADS, from baseline to 12 months was -1.32 (95% confidence interval: 
      2.61, -0.04; P = 0.044) in favor of the intervention group. One year post-stroke,
      4/85 (4.7%) patients in the intervention group and 12/89 (13.5%) in the control
      group suffered from depression (P = 0.045), while 7/85 (8.2%) patients in the
      intervention group and 13/89 (14.6%) patients in the control group suffered from
      anxiety (P = 0.19). CONCLUSION: A structured, multidisciplinary, multifactorial
      risk factor program including vascular risk factor management may be associated
      with reduced HADS scores and a lower prevalence of depressive symptoms one year
      after stroke.

PMID- 23957256
TI  - Postpartum uterine artery Doppler velocimetry among patients following a delivery
      complicated with preeclampsia.
AB  - OBJECTIVE: To evaluate postpartum uterine artery (UtA) velocimetry in patients
      following severe preeclampsia (PET) as compared with normotensive controls. STUDY
      DESIGN: Postpartum UtA velocimetry was obtained prospectively during the early
      postpartum period. The right and left UtA pulsatility index (PI) was measured and
      the presence of an early diastolic notch was noted. For categorical variables,
      the chi2 test or Fisher exact was used as appropriate and for continuous
      variables the t-test was used. The p value <0.05 was considered statistically
      significant. RESULTS: Thirty-one patients following severe PET and 52
      normotensive controls were included in the study. Following severe PET, higher
      rates of intrauterine growth restriction, cesarean delivery, preterm delivery and
      accordingly lower neonatal birth weight were noted. Postpartum UtA velocimetry
      measurements were performed on average 51.2 h after delivery (range 8-169). Right
      and left UtA PI was comparable between patients following severe PET and
      controls. The presence of unilateral and bilateral early diastolic notches were
      significantly higher in patients following severe PET. CONCLUSIONS: The
      pathophysiology of uterine involution and the physiologic return of the uterine
      arteries to the non-pregnant state may be different following severe PET.

PMID- 23957257
TI  - Reply to the comment from C Fiori and D Martinez on my article 'homoeopathy and
      consumers' right to know'.

PMID- 23957258
TI  - Morphological change of a laterally spreading rectal tumor over a short period.
AB  - BACKGROUND: Laterally spreading tumors (LSTs) are generally defined as
      superficial lesions >=10 mm in diameter that typically extend laterally rather
      than vertically along the colonic wall. LSTs are usually categorized into 2
      subtypes: granular type and nongranular type. Large nodules or depressed areas in
      granular-type LSTs (LST-Gs) are endoscopic findings of a cancerous component and
      sometimes represent submucosal invasion. However, the lateral growth and
      development of LST-Gs remains unclear. CASE PRESENTATION: This case report
      describes a case of 79-year-old woman who underwent total colonoscopy due to a
      positive fecal occult blood test and was detected a LST-G, about 30 mm in
      diameter in the lower rectum. The lesion consisted of not only aggregated small
      and large nodules typically seen in LST-Gs but also the hardly elevated flat
      parts. In the flat part, there were dilated round pits and no evident capillary
      vessels. Three months later, the flat part increased in height, the dilated round
      pits were partly replaced by type IIIL pits, and capillary vessels were evident.
      The lesion was removed by endoscopic submucosal dissection, and diagnosed
      pathologically as tubular adenoma. We performed the sequence analyses on KRAS,
      BRAF, NRAS and PIK3CA genes in flat part and nodular part separately, and a
      mutation of KRAS gene at codon 146 was observed at only nodular part, suggesting
      probable that nodular part be a precancerous lesion. CONCLUSION: This is a unique
      and suggestive case, providing information on progression of LST-Gs at the very
      early stage to carcinogenesis.

PMID- 23957259
TI  - Posthypnotic suggestion alters conscious color perception in an automatic manner.
AB  - The authors studied whether a posthypnotic suggestion to see a brief, masked
      target as gray can change the color experience of a hypnotic virtuoso. The
      visibility of the target was manipulated by varying the delay between the target
      and the mask that followed it. The virtuoso's subjective reports indicated that
      her conscious color experience was altered already at short delays between the
      target and the subsequent mask. The virtuoso's objectively measured pattern of
      responding under posthypnotic suggestion could not be mimicked either by control
      participants nor the virtuoso herself. Due to posthypnotic amnesia, the virtuoso
      was unaware of suggestions given during hypnosis. Importantly, the virtuoso could
      not alter her color perception without a hypnotic suggestion. These results
      suggest that hypnosis can affect even a highly automatic process such as color
      perception.

PMID- 23957260
TI  - The effective use of hypnosis in schizophrenia: structure and strategy.
AB  - Many schizophrenia patients seek hypnosis when they have not improved with
      psychopharmacological therapy. However, there has been controversy regarding the
      use and effectiveness of hypnosis in schizophrenia. Hypnotherapeutic methods such
      as direct and indirect suggestions, psycho-strengthening suggestions and imagery,
      hypnoprojective restructuring, guidance, and neutralization of affect associated
      with delusions have been effective in selected highly hypnotizable patients.
      Details of the hypnotherapeutic structure and strategy used for managing
      delusions in schizophrenia are presented with representative cases.

PMID- 23957261
TI  - Phenomenological aspects of hypnotic interactions: the effect of kinship.
AB  - This study analyzes the relationship of various measures of hypnosis as a
      function of kinship. Subjects with varying degrees of kinship (mono- and
      dizygotic twins, siblings, and parent-child pairs) participated. The Stanford
      Hypnotic Susceptibility Scale, Form A (SHSS:A), as well as other measures
      including the Dyadic Interactional Harmony (DIH) and the Phenomenology of
      Consciousness Inventory (PCI)-were used with both subjects and hypnosis
      practitioners. Findings indicated that the phenomenological experience of
      hypnosis is not determined genetically. The subjects apparently evaluated the
      session as related to the degree of kinship. MZ twins-on the basis of reactive
      interactional pattern-evaluate the hypnotic interaction similarly. This was not
      true for SHSS:A scores or the phenomenological aspects of the state (PCI). These
      findings were interpreted within the sociopsychobiological model of hypnosis.

PMID- 23957262
TI  - Shifting self, shifting memory: testing the self-memory system model with
      hypnotic identity delusions.
AB  - According to Conway's self-memory system (SMS) model, autobiographical memories
      may be facilitated, inhibited, or misremembered to be consistent with current
      self. In 3 experiments, the authors tested this by hypnotically suggesting an
      identity delusion and indexing whether this shift in self produced a
      corresponding shift in autobiographical memory. High hypnotizable participants
      displayed a compelling identity delusion and elicited specific autobiographical
      events that they could justify when challenged. These memories were
      reinterpretations of previous experiences that supported the suggested identity.
      Importantly, autobiographical memories that were no longer consistent with the
      hypnotically deluded self were less accessible than other memories. The authors
      discuss these findings in the context of Conway's SMS model and propose 2
      accounts of autobiographical remembering during hypnotic and clinical delusions.

PMID- 23957263
TI  - Hypnosis--there's an app for that: a systematic review of hypnosis apps.
AB  - This study systematically reviews the hypnosis apps available via iTunes that
      were compatible with iPhone or iPad. Of 1455 apps identified on iTunes, 407 met
      inclusion criteria and were further reviewed. Most common hypnosis app targets
      were weight loss (23%), boosting self-esteem (20%), and relaxation/stress
      reduction (19%); 83% of apps delivered hypnosis via audio track, and 37% allowed
      tailoring. Less than 14% of apps reported disclaimers. None of the apps reported
      having been tested for efficacy, and none reported being evidence based. Although
      apps have the potential to enhance hypnosis delivery, it seems as though
      technology has raced ahead of the supporting science. Recommendations from
      clinical researchers and policy makers are needed to inform responsible hypnosis
      app development and use.

PMID- 23957264
TI  - The effects of hypnosis on anxiety, depression, fatigue, and sleepiness in people
      undergoing hemodialysis: a clinical report.
AB  - This study investigated the effect of hypnosis on anxiety, depression, fatigue,
      and sleepiness in hemodialysis patients. Twenty-nine patients participated in the
      15-day study. A single hypnosis session was performed on Day 8. Anxiety,
      depression, fatigue, and sleepiness were measured at baseline, on Day 8, and on
      Day 15 (HADS, MFI, ESS). Daily fatigue was also measured numerically. Anxiety,
      depression, and sleepiness significantly decreased after hypnosis. Weekly
      measures of fatigue remained stable; however, daily fatigue decreased.

PMID- 23957266
TI  - Sn-Cu nanocomposite anodes for rechargeable sodium-ion batteries.
AB  - Sn0.9Cu0.1 nanoparticles were synthesized via a surfactant-assisted wet chemistry
      method, which were then investigated as an anode material for ambient temperature
      rechargeable sodium ion batteries. The Sn0.9Cu0.1 nanoparticle-based electrodes
      exhibited a stable capacity of greater than 420 mA h g(-1) at 0.2 C rate,
      retaining 97% of their maximum observed capacity after 100 cycles of sodium
      insertion/deinsertion. Their performance is considerably superior to electrodes
      made with either Sn nanoparticles or Sn microparticles. 

PMID- 23957267
TI  - Liposomes in drug delivery: a patent review (2007 - present).
AB  - INTRODUCTION: Drug therapy is frequently limited by the widespread
      biodistribution of the active agents and the little specificity for non-healthy
      cells. Therefore, inadequate drug concentrations result into the site of action,
      and severe toxicity may also arise. To address the problem, liposome-based
      medicines have tried to improve pharmacotherapy. AREAS COVERED: The review
      provides an updated revision of the lately published patents covering recent
      advances in liposome-based drug delivery. They are principally related to the
      control of drug biodistribution by using stealth, stimuli-sensitive and/or
      liposomal structures surface modified for ligand-mediated delivery. The
      contribution further highlights liposome-based theranosis. EXPERT OPINION:
      Liposomes have received great attention given their biocompatibility,
      biodegradability and targetability. From 2007 to present date, patent
      publications related to their use in drug delivery have shown the move towards
      more stable structures with optimized drug delivery capabilities, further
      combining passive and active targeting concepts to gain control of the in vivo
      fate. However, the introduction of all these liposomal structures in the disease
      arena is still a challenge. Two key aspects are the difficulty of identifying
      easy and economic synthesis conditions which can be scaled up in the
      pharmaceutical industry, and the need for complementary investigations
      illustrating risks of toxicity/immunogenicity.

PMID- 23957270
TI  - Influence of blocks' topologies on endothelial shear stress observed in CFD
      analysis of artery bifurcation.
AB  - It is well known that endothelial shear stress affects occurrence of plaque in
      arteries. Lack of a method for measuring this physical quantity limits scientific
      understanding of this phenomenon. Application of numerical methods in this area
      has considerable amount of experimental verifications in terms of quantities that
      can be measured (velocity, pressure). On that basis we can rely on the results of
      endothelial shear stress calculations. The literature mainly documents the
      application of numerical methods to average geometries. However, arterial
      bifurcations are patient-specific. Moreover, occurrence of disease significantly
      complicates the geometry of the arteries and bifurcations. A multiblock concept
      provides the necessary geometrical flexibility and computational efficiency to
      generate patient-specific finite element models. For a particular class of
      problems different topologies of blocks are possible. This paper provides an
      overview of the possible block topologies required in finite element modeling
      using multiblock approach. In order to obtain accurate results of endothelial
      shear stress, two most general topologies are examined by numerical calculations.
      Favorable topology of the blocks is implemented in in-house software stl2fem.

PMID- 23957269
TI  - Quantifying the contribution of long-range Saharan dust transport on particulate
      matter concentrations in Houston, Texas, using detailed elemental analysis.
AB  - The trans-Atlantic transport of North African dust by summertime trade winds
      occasionally increases ambient particulate matter (PM) concentrations in Texas
      above air quality standards. Exemptions from such exceedences can be sought for
      episodic events that are beyond regulatory control by providing qualitative
      supportive information such as satellite images and back-trajectories. Herein we
      demonstrate that chemical mass balancing can successfully isolate, differentiate,
      and quantify the relative contributions from local and global mineral dust
      sources through detailed measurements of a wide suite of elements in ambient PM.
      We identified a major dust storm originating in Northwest Africa in mid-July 2008
      which eventually impacted air quality in Houston during July 25, 26, and 27,
      2008. Daily PM2.5 and PM10 samples were collected at two sites in Houston over a
      2-week period encompassing the Saharan dust episode to quantify the transported
      mineral dust concentrations during this peak event. Average PM concentrations
      more than doubled during the Saharan intrusion compared with non-Saharan.
      Relative concentrations of several elements often associated with anthropogenic
      sources were significantly diluted by crustal minerals coincident with the large
      scale Saharan dust intrusion. During non-Saharan days, local mineral dust sources
      including cement manufacturing and soil and road dust contributed in total 26% to
      PM2.5 mass and 50% to PM10 mass; during the three-day Saharan episode the total
      dust contribution increased to 64% for PM2.5 and 85% for PM10. Importantly, this
      approach was also able to determine that local emissions of crustal minerals
      dominated the period immediately following the Saharan dust episode: simple
      quantification of bulk crustal materials may have misappropriated this elevated
      PM to trans-Atlantic transport of Saharan dust. 

PMID- 23957268
TI  - Managing sleep and wakefulness in a 24-hour world.
AB  - This article contributes to literature on the sociology of sleep by exploring the
      sleeping practices and subjective sleep experiences of two social groups: shift
      workers and students. It draws on data, collected in the UK from 25 semi
      structured interviews, to discuss the complex ways in which working patterns and
      social activities impact upon experiences and expectations of sleep in our wired
      awake world. The data show that, typically, sleep is valued and considered to be
      important for health, general wellbeing, appearance and physical and cognitive
      functioning. However, sleep time is often cut back on in favour of work demands
      and social activities. While shift workers described their efforts to fit in an
      adequate amount of sleep per 24-hour period, for students, the adoption of a
      flexible sleep routine was thought to be favourable for maintaining a work-social
      life balance. Collectively, respondents reported using a wide range of
      strategies, techniques, technologies and practices to encourage, overcome or
      delay sleep(iness) and boost, promote or enhance wakefulness/alertness at
      socially desirable times. The analysis demonstrates how social context impacts
      not only on how we come to think about sleep and understand it, but also how we
      manage or self-regulate our sleeping patterns. 

PMID- 23957271
TI  - Emotional availability in psychotherapy: the usefulness and validity of the
      emotional availability scales for analyzing the psychotherapeutic relationship.
AB  - The aim of this study was to assess whether a modified version of the Emotional
      Availability Scales (EAS), created to assess interaction quality between parents
      and children, could be applied to psychotherapy sessions and whether emotional
      availability (EA), as assessed by the modified EAS-T, was associated with client-
      and therapist-rated working alliance. EAS-T was used to assess 42 sessions from
      16 therapies. The therapies came from the LURIPP project, comparing IPT with BRT
      for depressed clients. The results showed that sessions could be reliably rated
      with EAS-T. Most rating scales had acceptable variance. The client's perception
      of task alliance was associated with several of the EA subscales (sensitivity,
      nonhostility, responsiveness) assessed over therapies, whereas the perception of
      bond was associated with Structure on EAS.

PMID- 23957272
TI  - Effects of reference analgesics and psychoactive drugs on the noxious heat
      threshold of mice measured by an increasing-temperature water bath.
AB  - The study aimed at validating an increasing-temperature water bath suitable for
      determining the noxious heat threshold for use in mice. The noxious heat
      threshold was determined by immersing the tail of the gently held awake mouse
      into a water container whose temperature was near-linearly increased at a rate of
      24 degrees C/min. until the animal withdrew its tail, that is, heating attained
      the noxious threshold. The effects of standard analgesic, neuroleptic and
      anxiolytic drugs were investigated in a parallel way on both the noxious heat
      threshold and the psychomotor activity assessed by the open field test. Morphine,
      diclofenac and metamizol (dipyrone) elevated the heat threshold of mice with
      minimum effective doses of 6, 30 and 1000 mg/kg i.p., respectively. These doses
      of morphine and diclofenac failed to induce any remarkable effect on psychomotor
      activity in the open field test while that of metamizol exerted a profound
      inhibition. The anxiolytic diazepam and the neuroleptic droperidol at doses
      evoking a mild and moderate, respectively, psychomotor inhibition failed to alter
      the heat threshold. Combination of a subliminal dose of morphine (regarding both
      antinociceptive and psychomotor inhibitory action) with diclofenac, metamizol,
      diazepam or droperidol at doses also subliminal regarding the thermal
      antinociceptive effect elevated the noxious heat threshold without major
      additional effects in the open field test. It is concluded that the increasing
      temperature water bath is suitable for studying the thermal antinociceptive
      effects of morphine and diclofenac as well as the morphine-sparing action of
      diclofenac, metamizol, droperidol and diazepam. Behavioural testing is
      recommended when testing analgesics. 

PMID- 23957273
TI  - Strain dependence of adolescent Cannabis influence on heroin reward and
      mesolimbic dopamine transmission in adult Lewis and Fischer 344 rats.
AB  - Adolescent Cannabis exposure has been hypothesized to act as a gateway to opiate
      abuse. In order to investigate the role of genetic background in cannabinoid
      opiate interactions, we studied the effect of Delta(9) -tetrahydrocannabinol
      (THC) exposure of adolescent Lewis and Fischer 344 rats on the responsiveness of
      accumbens shell and core dopamine (DA), as monitored by microdialysis, to THC and
      heroin at adulthood. Heroin reward and reinstatement by heroin priming were
      studied by conditioned place preference (CPP) and cognitive and emotional
      functions by object recognition, Y maze and elevated plus maze paradigms. THC
      stimulated shell DA in Lewis but not in Fischer 344 rats. Adolescent THC exposure
      potentiated DA stimulant effects of heroin in the shell and core of Lewis and
      only in the core of Fischer 344 rats. Control Lewis rats developed stronger CPP
      to heroin and resistance to extinction compared with Fischer 344 strain. In Lewis
      rats, THC exposure did not affect heroin CPP but potentiated the effect of heroin
      priming. In Fischer 344 rats, THC exposure increased heroin CPP and made it
      resistant to extinction. Lewis rats showed seeking reactions during extinction
      and hedonic reactions in response to heroin priming. Moreover, adolescent THC
      exposure affected emotional function only in Lewis rats. These observations
      suggest that long-term effects of Cannabis exposure on heroin addictive liability
      and emotionality are dependent on individual genetic background. 

PMID- 23957274
TI  - Malignant Catarrhal Fever: An Emerging Disease in the African Buffalo (Syncerus
      caffer).
AB  - Within the tribe Bovini in the subfamily Bovinae, the water buffalo (Bubalus
      Bubalis), American bison (Bison bison), European bison (Bubalus bonasus) and yak
      (Bos grunniens) are recognized as species highly susceptible to malignant
      catarrhal fever (MCF). In contrast, the lack of reports describing clinical MCF
      in the African buffalo (Syncerus caffer) whether free ranging or captive has led
      to a perception that African buffaloes are resistant to MCF. During the last
      decade, several cases of MCF in African buffaloes were confirmed in South Africa
      and experience with seven of these cases is described in this report. Detection
      of viral nucleic acid in blood or tissues was successful in six African buffaloes
      that suffered from clinical signs compatible with MCF. Four were positive for
      infection with ovine herpesvirus type 2 (the causative virus of sheep-associated
      MCF), and two were positive for alcelaphine herpesvirus type 1 (causative virus
      of wildebeest-associated MCF). Histopathological examination of tissue samples
      from all the animals yielded typical lesions that were consistent with those
      described for MCF in domestic cattle. Developments in the management of African
      buffaloes translocated from their traditional habitats have likely contributed to
      the identification of another susceptible host in the subfamily Bovinae. 

PMID- 23957275
TI  - Preparation of spiro[4.4]oxaphospholene and -azaphospholene systems from
      carbohydrate templates.
AB  - Introduction of a spiro-phosphorus cycle in position 3 of monosaccharidic
      derivatives was studied starting from cyanohydrin or aminonitrile A. A two-step
      procedure involving (i) phosphonylation and (ii) carbanion-mediated phosphonate
      intramolecular cyclization (denoted CPIC) was used. The necessity of having an
      electron-withdrawing group alpha to the phosphorus atom in order to avoid
      undesired reactions was demonstrated. 

PMID- 23957276
TI  - Shifting and extension of phenological periods with increasing temperature along
      elevational transects in southern Bavaria.
AB  - The impact of global warming on phenology has been widely studied, and almost
      consistently advancing spring events have been reported. Especially in alpine
      regions, an extraordinary rapid warming has been observed in the last decades.
      However, little is known about phenological phases over the whole vegetation
      period at high elevations. We observed 12 phenological phases of seven tree
      species and measured air temperature at 42 sites along four transects of about
      1000 m elevational range in the years 2010 and 2011 near Garmisch-Partenkirchen,
      Germany. Site- and species-specific onset dates for the phenological phases were
      determined and related to elevation, temperature lapse rates and site-specific
      temperature sums. Increasing temperatures induced advanced spring and delayed
      autumn phases, in which both yielded similar magnitudes. Delayed leaf senescence
      could therefore have been underestimated until now in extending the vegetation
      period. Not only the vegetation period, but also phenological periods extended
      with increasing temperature. Moreover, sensitivity to elevation and temperature
      strongly depends on the specific phenological phase. Differences between species
      and groups of species (deciduous, evergreen, high elevation) were found in onset
      dates, phenological response rates and also in the effect of chilling and forcing
      temperatures. Increased chilling days highly reduced forcing temperature
      requirements for deciduous trees, but less for evergreen trees. The problem of
      shifted species associations and phenological mismatches due to species-specific
      responses to increasing temperature is a recent topic in ecological research.
      Therefore, we consider our findings from this novel, dense observation network in
      an alpine area of particular importance to deepen knowledge on phenological
      responses to climate change.

PMID- 23957277
TI  - Quantitative proteomic analysis of microdissected breast cancer tissues:
      comparison of label-free and SILAC-based quantification with shotgun, directed,
      and targeted MS approaches.
AB  - Quantitative proteomics plays an important role in validation of breast-cancer
      related biomarkers. In this study, we systematically compared the performance of
      label-free quantification (LFQ) and SILAC with shotgun and directed methods for
      quantifying breast-cancer-related markers in microdissected tissues. We show that
      LFQ leads to slightly higher coefficient of variation (CV) for protein
      quantification (median CV = 16.3%) than SILAC quantification (median CV = 13.7%)
      (P < 0.0001), but LFQ method enables ~60% more protein quantification and is also
      more reproducible (~20% more proteins were quantified in all replicate samples).
      Furthermore, we describe a method to accurately quantify multiple proteins within
      one pathway, that is, "focal adhesion pathway", in trace amounts of breast cancer
      tissues using a SILAC-based SRM assay. Using this SILAC-based SRM assay, we
      precisely quantified five "focal adhesion" proteins with good quantitative
      precision (CV range: 2.4-5.9%) in replicate whole tissue lysate samples and
      replicate microdissected samples (CV range: 5.8-16.1%). Our results show that in
      microdissected breast cancer tissues LFQ in combination with shotgun proteomics
      performed the best overall and is therefore suitable for both biomarker discovery
      and validation in these types of specimens. The SILAC-based SRM method can be
      used for the development of clinically relevant protein assays in tumor biopsies.

PMID- 23957278
TI  - Keys for the existence of stable dimers of bis-tetrathiafulvalene (bis-TTF)
      functionalized molecular clips presenting [TTF](*+)...[TTF](*+) long, multicenter
      bonds at room temperature.
AB  - A systematic theoretical and computational investigation is performed to
      determine the keys governing the existence, in acetonitrile solutions, of dimers
      of bis-tetrathiafulvalene (bis-TTF)-functionalized diphenylglycoluril molecular
      clips (clip2(n+)) that are stable at room temperature for n <= 4. Although the
      experimental structure of these dimers in solution is unknown, electronic
      absorption studies suggest that they have [TTF](l+)...[TTF](m+) interactions that
      are preserved at room temperature (note that when l = m = 1 these interactions
      become long, multicenter bonds). In good agreement with the interpretation of the
      experimental spectroscopic data, all clip2(n+) dimers whose charge is <=4 present
      an optimum geometry that, in all cases, has three short interfragment
      [TTF](l+)...[TTF](m+) interactions. The computed DeltaG(298 K) for these optimum
      structures matches the available experimental data on the stability of these
      dimers. Such optimum geometry, combined with the zwitterionic character of the
      electron distribution in monomers and dimers (most of the net positive charge is
      equally distributed among the TTF groups, while a 1- au charge is located in the
      central fused five-membered rings) allows the formation of a maximum of two long,
      multicenter [TTF](*+)...[TTF](*+) bonds when all TTF groups host a 1+ au of
      charge, as in clip2(4+). However, these long, multicenter bonds alone do not
      account for the stability of clip2(n+) dimers at room temperature. Instead, the
      studies carried out here trace the origin of their stability to (1) the
      zwitterionic character of their charge distribution, (2) the proper geometrical
      shape of the interacting monomers, which allows the intercalation of their arms,
      thus making possible the simultaneous formation of two short contacts, both
      involving the positively charged TTF group of one monomer and the negatively
      charged central ring of the other, (3) the simultaneous presence of three short
      contacts among the TTF groups in the optimum geometry of the clip2(n+) dimers,
      which become two long, multicenter bonds and one van der Waals interaction when
      the four TTF groups host a 1+ charge, and (4) the net stabilizing effect of the
      solvent. 

PMID- 23957279
TI  - Is memory search governed by universal principles or idiosyncratic strategies?
AB  - Laboratory paradigms have provided an empirical foundation for much of
      psychological science. Some have argued, however, that such paradigms are highly
      susceptible to idiosyncratic strategies and that many findings do not reflect
      fundamental cognitive principles but are instead artifacts of averaging across
      participants who employ different strategies. We developed a set of techniques to
      rigorously test the extent to which average data are distorted by such strategy
      differences and applied these techniques to free recall data from the Penn
      Electrophysiology of Encoding and Retrieval Study. Recall initiation showed
      evidence of subgroups: The majority of participants initiated recall from the
      last item in the list, but one subgroup showed elevated initiation probabilities
      for items 2 to 4 positions back from the end of the list, and another showed
      elevated probabilities for the beginning of the list. By contrast, serial
      position curves and temporal and semantic clustering functions were remarkably
      consistent, with almost every participant exhibiting a recognizable version of
      the average function, suggesting that these functions reflect fundamental
      principles of the memory system. The approach taken here can serve as a model for
      evaluating the extent to which other laboratory paradigms are influenced by
      individual differences in strategy use.

PMID- 23957280
TI  - The language of magnitude comparison.
AB  - When 2 objects differ in magnitude, their relation can be described with a
      "smaller" comparative (e.g., less, shorter, lower) or a "larger" comparative
      (e.g., more, taller, higher). We show that, across multiple dimensions and tasks,
      English speakers preferentially use the latter. In sentence completion tasks,
      this higher use of larger comparatives (HULC) effect is more pronounced when the
      larger item is presented on the left (for simultaneous presentation) or second
      (for sequential presentation). The HULC effect is not diminished by making the 2
      items more similar, but it is somewhat lessened when both objects are of low
      magnitude. These results illuminate the processes underlying the judgment and
      representation of relative magnitudes.

PMID- 23957281
TI  - The influence of context boundaries on memory for the sequential order of events.
AB  - Episodic memory allows people to reexperience the past by recovering the
      sequences of events that characterize those prior experiences. Although
      experience is continuous, people are able to selectively retrieve and
      reexperience more discrete episodes from their past, raising the possibility that
      some elements become tightly related to each other in memory, whereas others do
      not. The current series of experiments was designed to ask how shifts in context
      during an experience influence how people remember the past. Specifically, we
      asked how context shifts influence the ability to remember the relative order of
      past events, a hallmark of episodic memory. We found that memory for the order of
      events was enhanced within, rather than across, context shifts, or boundaries
      (Experiment 1). Next, we showed that this relative enhancement in order memory
      was eliminated when across-item associative processing was disrupted (Experiment
      2), suggesting that context shifts have a selective effect on sequential binding.
      Finally, we provide evidence that the act of making order memory judgments
      involves the reactivation of representations that bridged the tested items
      (Experiment 3). Together, these data suggest that boundaries may serve to parse
      continuous experience into sequences of contextually related events and that this
      organization facilitates remembering the temporal order of events that share the
      same context.

PMID- 23957282
TI  - Behavioral components of impulsivity.
AB  - Acting in accord with long-term goals requires control of interfering impulses,
      the success of which depends on several different processes. Using a structural
      equation modeling approach, we investigated 5 behavioral components of
      impulsivity: the control of stimulus interference, proactive interference, and
      response interference, as well as decisional and motivational impulsivity.
      Results support the existence of 5 correlated but separable components of
      impulsive behavior. The present study is the 1st to demonstrate the separability
      of stimulus and response interference. It also supports the notion that control
      of response-related interference is not a unitary construct: Response-selection
      demands were separable from those of withholding or stopping. Relations between
      behavioral impulsivity components and self-report measures of impulsivity were
      largely absent. We conclude that as the construct of impulsivity has been
      extended to describe an increasingly diverse set of phenomena and processes, it
      has become too broad to be helpful in guiding future research.

PMID- 23957283
TI  - The nondiscriminating heart: lovingkindness meditation training decreases
      implicit intergroup bias.
AB  - Although meditation is increasingly accepted as having personal benefits, less is
      known about the broader impact of meditation on social and intergroup relations.
      We tested the effect of lovingkindness meditation training on improving implicit
      attitudes toward members of 2 stigmatized social outgroups: Blacks and homeless
      people. Healthy non-Black, nonhomeless adults (N = 101) were randomly assigned to
      1 of 3 conditions: 6-week lovingkindness practice, 6-week lovingkindness
      discussion (a closely matched active control), or waitlist control. Decreases in
      implicit bias against stigmatized outgroups (as measured by Implicit Association
      Test) were observed only in the lovingkindness practice condition. Reduced
      psychological stress mediated the effect of lovingkindness practice on implicit
      bias against homeless people, but it did not mediate the reduced bias against
      Black people. These results suggest that lovingkindness meditation can improve
      automatically activated, implicit attitudes toward stigmatized social groups and
      that this effect occurs through distinctive mechanisms for different stigmatized
      social groups.

PMID- 23957284
TI  - The role of belief in occurrence within autobiographical memory.
AB  - This article examines the idea that believing that events occurred in the past is
      a non-memorial decision that reflects underlying processes that are distinct from
      recollecting events. Research on autobiographical memory has often focused on
      events that are both believed to have occurred and remembered, thus tending to
      overlook the distinction between autobiographical belief and recollection.
      Studying event representations such as false memories, believed-not-remembered
      events, and non-believed memories shows the influence of non-memorial processes
      on evaluations of occurrence. Believing that an event occurred and recollecting
      an event may be more strongly dissociated than previously stated. The relative
      independence of these constructs was examined in 2 studies. In Study 1, multiple
      events were cued, and then each was rated on autobiographical belief,
      recollection, and other memory characteristics. In Study 2, participants
      described a nonbelieved memory, a believed memory, and a believed-not-remembered
      event, and they made similar ratings. In both studies, structural equation
      modeling techniques revealed distinct belief and recollection latent variables.
      Modeling the predictors of these factors revealed a double dissociation:
      Perceptual, re-experiencing, and emotional features predicted recollection and
      not belief, whereas event plausibility strongly predicted belief and weakly
      predicted recollection. The results show that judgments of autobiographical
      belief and recollection are distinct, that each is influenced by different
      sources of information and processes, and that the strength of their relationship
      varies depending on the type of event under study. The concept of
      autobiographical belief is elaborated, and implications of the findings are
      discussed in relation to decision making about events, social influence on
      memory, metacognition, and recognition processes.

PMID- 23957285
TI  - The context repetition effect: predicted events are remembered better, even when
      they don't happen.
AB  - A key function of the medial temporal lobe (MTL) is to generate predictions based
      on prior experience (Bar, 2009). We propose that these MTL-generated predictions
      guide learning, such that predictions from memory influence memory itself.
      Considering this proposal within a context-based theory of learning and memory
      leads to the unique hypothesis that the act of predicting an event from the
      current context can enhance later memory for that event, even if the event does
      not actually occur. We tested this hypothesis using a novel paradigm in which the
      contexts of some stimuli were repeated during an incidental learning task,
      without the stimuli themselves being repeated. Results from 4 experiments show
      clear behavioral evidence in support of this hypothesis: Participants were more
      likely to remember once-presented items if the temporal contexts of those items
      were later repeated. However, this effect only occurred in learning environments
      where predictions could be helpful.

PMID- 23957286
TI  - Ligand binding site detection by local structure alignment and its performance
      complementarity.
AB  - Accurate determination of potential ligand binding sites (BS) is a key step for
      protein function characterization and structure-based drug design. Despite
      promising results of template-based BS prediction methods using global structure
      alignment (GSA), there is room to improve the performance by properly
      incorporating local structure alignment (LSA) because BS are local structures and
      often similar for proteins with dissimilar global folds. We present a template
      based ligand BS prediction method using G-LoSA, our LSA tool. A large benchmark
      set validation shows that G-LoSA predicts drug-like ligands' positions in single
      chain protein targets more precisely than TM-align, a GSA-based method, while the
      overall success rate of TM-align is better. G-LoSA is particularly efficient for
      accurate detection of local structures conserved across proteins with diverse
      global topologies. Recognizing the performance complementarity of G-LoSA to TM
      align and a nontemplate geometry-based method, fpocket, a robust consensus
      scoring method, CMCS-BSP (Complementary Methods and Consensus Scoring for ligand
      Binding Site Prediction), is developed and shows improvement on prediction
      accuracy. 

PMID- 23957287
TI  - Determinants of extinction-colonization dynamics in Mediterranean butterflies:
      the role of landscape, climate and local habitat features.
AB  - Many species are found today in the form of fragmented populations occupying
      patches of remnant habitat in human-altered landscapes. The persistence of these
      population networks requires a balance between extinction and colonization events
      assumed to be primarily related to patch area and isolation, but the contribution
      of factors such as the characteristics of patch and matrix habitats, the species'
      traits (habitat specialization and dispersal capabilities) and variation in
      climatic conditions have seldom been evaluated simultaneously. The identification
      of environmental variables associated with patch occupancy and turnover may be
      especially useful to enhance the persistence of multiple species under current
      global change. However, for robust inference on occupancy and related parameters,
      we must account for detection errors, a commonly overlooked problem that leads to
      biased estimates and misleading conclusions about population dynamics. Here, we
      provide direct empirical evidence of the effects of different environmental
      variables on the extinction and colonization rates of a rich butterfly community
      in the western Mediterranean. The analysis was based on a 17-year data set
      containing detection/nondetection data on 73 butterfly species for 26 sites in
      north-eastern Spain. Using multiseason occupancy models, which take into account
      species' detectability, we were able to obtain robust estimates of local
      extinction and colonization probabilities for each species and test the potential
      effects of site covariates such as the area of suitable habitat, topographic
      variability, landscape permeability around the site and climatic variability in
      aridity conditions. Results revealed a general pattern across species with local
      habitat composition and landscape features as stronger predictors of occupancy
      dynamics compared with topography and local aridity. Increasing area of suitable
      habitat in a site strongly decreased local extinction risks and, for a number of
      species, both higher amounts of suitable habitat and more permeable landscapes
      increased colonization rates. Nevertheless, increased topographic variability
      decreased the extinction risk of bad dispersers, a group of species with
      significantly lower colonization rates. Our models predicted higher sensitivity
      of the butterfly assemblages to deterministic changes in habitat features rather
      than to stochastic weather patterns, with some relationships being clearly
      dependent on the species' traits. 

PMID- 23957288
TI  - Alice in Wonderland syndrome as aura of migraine.
AB  - Alice in Wonderland syndrome (AIWS), named for Lewis Carroll's titular character,
      is a disorder characterized by transient episodes of visual hallucinations and
      perceptual distortions, during which objects or body parts are perceived as
      altered in various ways (metamorphopsia), including enlargement (macropsia) or
      reduction (micropsia) in the perceived size of a form. Migraine aura is a
      transient neurological symptom that most commonly involves the visual fields and
      occurs before the headache phase. Aura symptoms include the perception of
      flashing lights that begin in the center of vision and expand in jagged patterns
      out into the periphery. Symptoms may be somatosensory, such as numbness and
      tingling in the lips or fingers. They may also involve a profound alteration of
      the perception of space and time (the "Alice in Wonderland" syndrome). In this
      article, we present a child had Alice in Wonderland syndrome as aura of migraine.

PMID- 23957289
TI  - The effect of Cirsium arvense extract on antioxidant status in quail.
AB  - 1. The herb Creeping Thistle, Cirsium arvense (C. arvense), has been used in folk
      medicine due to its antioxidant and anti-inflammatory effects. 2. The aim of this
      study was to investigate the effects of dietary C. arvense extract
      supplementation on performance, egg quality, nutrient digestibility and
      antioxidant status in quail. 3. Quails (n = 150) were allocated randomly to one
      of the three dietary treatments: basal diet and basal diet enriched with 100 and
      200 mg C. arvense extract per kg diet. 4. Dietary enrichment with C. arvense
      extract altered neither performance and egg quality parameters nor nutrient
      digestibility. Although there were no changes in concentrations of vitamin A and
      E in serum, liver and egg yolk, supplemental C. arvense extract decreased MDA
      concentrations in serum, liver and egg yolk by 39.3, 40.5 and 51.5%,
      respectively, in a dose-response manner. As supplemental C. arvense extract
      increased to 200 mg/kg, the activity of hepatic SOD, CAT and GSH-Px increased by
      14.5, 17.4 and 35.5%, respectively. 5. Addition of C. arvense extract up to 200
      mg to per kg diet enhanced antioxidant status in laying quail and their eggs,
      without affecting performance and other egg quality parameters. 6. Future studies
      are needed to elucidate the mechanism behind the antioxidant effects of C.
      arvense extract. 

PMID- 23957290
TI  - Blueberries prevent the effect of intermittent hypobaric hypoxia in rat
      epididymis.
AB  - Intermittent hypobaric hypoxia (IHH) induced a decrease in sperm count and
      oxidative damage in epididymis. We have previously demonstrated that a blueberry
      enriched polyphenol extract (BB-4) reduced the adverse effects of oxidative
      stress in rat testis under hypobaric hypoxia. The aim of this study was to
      evaluate whether BB-4 could reverse oxidative stress in epididymis. To evaluate
      the protective role of BB-4 in epididymis, male rats were exposed to IHH. Lipid
      peroxidation, (LPO) expression and activity of glutathione reductase (GR) were
      evaluated. Our results showed a reduction in LPO and a decrease in GR activity in
      rat epididymis exposed to IHH. These results suggest that BB-4 can prevent the
      effects of IHH in rat epididymis. 

PMID- 23957291
TI  - The impact of obesity on sepsis mortality: a retrospective review.
AB  - BACKGROUND: Recent sepsis guidelines have focused on the early identification and
      risk stratification of patients on presentation. Obesity is associated with
      alterations in multiple inflammatory regulators similar to changes seen in
      sepsis, suggesting a potential interaction between the presence of obesity and
      the severity of illness in sepsis. METHODS: We performed a retrospective chart
      review of patients admitted with a primary billing diagnosis of sepsis at a
      single United States university hospital from 2007 to 2010. Seven hundred and
      ninety-two charts were identified meeting inclusion criteria. Obesity was defined
      as a body mass index (BMI) >= 30 kg/m2. The data recorded included age, race,
      sex, vital signs, laboratory values, length of stay, comorbidities, weight,
      height, and survival to discharge. A modified APACHE II score was calculated to
      estimate disease severity. The primary outcome variable was inpatient mortality.
      RESULTS: Survivors had higher average BMI than nonsurvivors (27.6 vs. 26.3 kg/m2,
      p = 0.03) in unadjusted analysis. Severity of illness and comorbid conditions
      including cancer were similar across BMI categories. Increased incidence of
      diabetes mellitus type 2 was associated with increasing BMI (p < 0.01) and was
      associated with decreased mortality, with an odds ratio of 0.53 compared with
      nondiabetic patients. After adjusting for age, gender, race, severity of illness,
      length of stay, and comorbid conditions, the trend of decreased mortality for
      increased BMI was no longer statistically significant, however diabetes continued
      to be strongly protective (odds ratio 0.52, p = 0.03). CONCLUSIONS: This
      retrospective analysis suggests obesity may be protective against mortality in
      septic inpatients. The protective effect of obesity may be dependent on diabetes,
      possibly through an unidentified hormonal intermediary. Further prospective
      studies are necessary to elaborate the specific mechanism of this protective
      effect.

PMID- 23957292
TI  - Lys1110 of TRPM2 is critical for channel activation.
AB  - TRPM2 (transient receptor potential melastatin 2) is a non-selective Ca2+
      permeable cation channel activated by ADPR (adenosine diphosphoribose) and H2O2.
      It is widely expressed in mammalian cells and plays an important role in the
      regulation of various cell functions. However, the mechanisms of TRPM2 channel
      activation are not fully understood. Previously, we reported that TRPM2 channel
      activation is induced by high intracellular Cl- concentration. In the present
      study, we investigated the functional role of Lys1110 in the membrane-proximal C
      terminal region by site-directed mutagenesis. Replacement of the positively
      charged amino acid lysine (Lys1110) with the neutrally charged amino acid
      asparagine (K1110N) or the negatively charged amino acid glutamic acid (K1110E)
      generated mutants that failed to induce an increase in free cytosolic calcium
      concentration ([Ca2+]i) not only by intracellular injection of Cl-, but also by
      H2O2 or ADPR. However, a mutant generated by replacing the lysine residue with a
      positively charged amino acid arginine (K1110R) displayed channel activity
      similar to wild-type TRPM2. Interestingly, in the K1107N/K1110N double-point
      mutant, the impaired function of the K1110N mutant in response to ADPR and H2O2,
      but not to Cl-, was recovered. There were no changes in protein expression,
      membrane trafficking and oligomerization of the mutant channels. The extent of
      [Ca2+]i increase by H2O2 in HEK (human embryonic kidney)-293 cells expressing
      TRPM2 mutants was well correlated with the degree of susceptibility to H2O2
      induced cell death. These results display the crucial role of a positively
      charged amino acid residue at position 1110 for TRPM2 channel activity. 

PMID- 23957293
TI  - Automated measurement of sFlt1, PlGF and sFlt1/PlGF ratio in differential
      diagnosis of hypertensive pregnancy disorders.
AB  - OBJECTIVES: The utility of angiogenic and antiangiogenic biomarkers as diagnostic
      tools in preeclampsia (PE) has been shown in previous studies. Our study's aim
      was to evaluate the use of automated measurement of sFlt1, PlGF and their ratio
      (sFlt1/PlGF) in differential diagnosis of hypertensive pregnancy disorders.
      PATIENTS/METHODS: Sixty-four patients with PE/HELLP, 18 with pregnancy-induced
      hypertension (PIH), 22 with gestational proteinuria (GP) and 232 controls were
      investigated. The PE/HELLP group was divided into mild PE (mPE, n=31), severe PE
      (sevPE, n=20), superimposed PE (supPE, n=7) and HELLP syndrome (n=6). sFlt1 and
      PlGF were measured in serum samples on an automated platform. Statistical
      analysis was performed using parametric and non-parametric methods, ROC analysis
      and logistic regression method. RESULTS: PE patients showed higher sFlt1 and
      ratio and lower PlGF than controls (median +/- SEM in pg/mL; 10888 +/- 878 versus
      2456 +/- 116; 268 +/- 39 versus 16 +/- 2 and 68 +/- 6 versus 439 +/- 37, each
      p<0.001), subgroups showed similar differences in ratios (median +/- SEM; supPE:
      202 +/- 110; mPE: 137 +/- 27; sevPE: 497 +/- 91; HELLP syndrome: 254 +/- 72
      versus controls 16 +/- 2, each p<0.001). ROC analysis showed best performance for
      sFlt1/PlGF (AUC all PE: ratio 96.4%, sFlt1 92.8%, PlGF 92.4%, supPE: ratio 93.6%,
      mPE: ratio 94.8%, sevPE: ratio 99.4%, HELLP: ratio 98.6%, each versus controls).
      Patients with PIH and GP showed significant differences compared to controls (p
      <= 0.01, respectively), mPE (p <= 0.007), sevPE (p<0.001) and HELLP syndrome (p
      <= 0.003). CONCLUSION: The automated measurement of sFlt1/PlGF is a reliable
      diagnostic tool in differential diagnosis of hypertensive pregnancy disorders and
      gives additional valuable information for clinical management.

PMID- 23957294
TI  - Therapeutic targets associated to E-cadherin dysfunction in gastric cancer.
AB  - INTRODUCTION: Epithelial cadherin (E-cadherin) plays a key role in epithelial
      cell-cell adhesion, contributing to tissue differentiation and homeostasis.
      Throughout the past decades, research has shed light on the molecular mechanisms
      underlying E-cadherin's role in tumor progression, namely in invasion and
      metastization. Emerging evidence established E-cadherin as a tumor suppressor and
      suggests that targeting E-cadherin or downstream signaling molecules may
      constitute effective cancer therapeutics. AREAS COVERED: This review aims to
      cover E-cadherin-mediated signaling during cancer development and progression and
      highlight putative therapeutic targets. EXPERT OPINION: Reconstitution of E
      cadherin expression or targeting of E-cadherin downstream molecules holds promise
      in cancer therapies. Considering the high frequency of CDH1 promoter
      hypermethylation as a second hit in malignant lesions from hereditary diffuse
      gastric cancer patients, histone deacetylase inhibitors are potential therapeutic
      agents in combination with conventional chemotherapy, specifically in initial
      tumor stages. Concerning E-cadherin-mediated signaling, we propose that HER
      receptors (as epidermal growth factor receptor) and Notch downstream targets are
      clinically relevant and should be considered in gastric cancer therapeutics and
      control.

PMID- 23957296
TI  - Methylmercury targets photoreceptor outer segments.
AB  - Human populations experience widespread low level exposure to organometallic
      methylmercury compounds through consumption of fish and other seafood. At higher
      levels, methylmercury compounds specifically target nervous systems, and among
      the many effects of their exposure are visual disturbances, including blindness,
      which previously were thought to be due to methylmercury-induced damage to the
      visual cortex. Here, we employ high-resolution X-ray fluorescence imaging using
      beam sizes of 500 * 500 and 250 * 250 nm(2) to investigate the localization of
      mercury at unprecedented resolution in sections of zebrafish larvae ( Danio rerio
      ), a model developing vertebrate. We demonstrate that methylmercury specifically
      targets the outer segments of photoreceptor cells in both the retina and pineal
      gland. Methylmercury distribution in both tissues was correlated with that of
      sulfur, which, together with methylmercury's affinity for thiolate donors,
      suggests involvement of protein cysteine residues in methylmercury binding. In
      contrast, in the lens, the mercury distribution was different from that of
      sulfur, with methylmercury specifically accumulating in the secondary fiber cells
      immediately underlying the lens epithelial cells rather than in the lens
      epithelial cells themselves. Since methylmercury targets two main eye tissues
      (lens and photoreceptors) that are directly involved in visual perception, it now
      seems likely that the visual disruption associated with methylmercury exposure in
      higher animals including humans may arise from direct damage to photoreceptors,
      in addition to injury of the visual cortex. 

PMID- 23957297
TI  - ATR-IR study of ozone initiated heterogeneous oxidation of squalene in an indoor
      environment.
AB  - There has been a surge of interest in interfacial ozone chemistry for its
      application in indoor air quality and public health. Squalene, one of the most
      abundant ozone reactive constituents in an indoor environment, has received
      increasing attention lately, and a number of studies have been devoted to its
      heterogeneous interaction with ozone in actual and simulated settings. At
      present, there is still a large discrepancy in the measurement of the reactive
      uptake coefficient of ozone onto a squalene surface, and knowledge about this
      system remains incomplete. In this work, we investigated the ozone initiated
      heterogeneous oxidation of squalene using attenuated total reflection infrared
      spectroscopy (ATR-IR). We measured pseudo-first-order rate constants and uptake
      coefficients based on time dependent absorbance changes in C?C (1668 cm(-1)) and
      C?O (1730 cm(-1)) vibration bands. The uptake coefficients are (1.7 +/- 0.2) *
      10(-4) from the C?C band and (5.1 +/- 0.7) * 10(-4) from the C?O band. The latter
      is likely an upper limit of reaction probability for ozone uptake onto squalene.
      Studies of temperature (5-32  degrees C) and relative humidity (0 and 80% RH)
      dependence revealed that indoor temperatures and RHs did not affect reaction
      kinetics. The insignificant RH effect is probably due to the weak interaction
      between water and squalene molecules. We quantitatively characterized the
      hydrophilicity and redox activity of squalene before and after exposure to ozone
      for the first time, and observed considerable enhancements in both hydrophilicity
      and redox activity during reaction. This may imply that ozone initiated
      heterogeneous oxidation could pose a higher public health risk in an indoor
      environment, and it may help explain some of the adverse health effects
      associated with elevated indoor pollutants. 

PMID- 23957298
TI  - Impact of PECS tablet computer app on receptive identification of pictures given
      a verbal stimulus.
AB  - OBJECTIVE: The purpose of this brief report was to determine the effect on
      receptive identification of photos of a tablet computer-based augmentative and
      alternative communication (AAC) system with voice output. METHODS: A multiple
      baseline single-case experimental design across vocabulary words was implemented.
      One participant, a preschool-aged boy with autism and little intelligible verbal
      language, was included in the study. RESULTS: Although a functional relation
      between the intervention and the dependent variable was not established, the
      intervention did appear to result in mild improvement for two of the three
      vocabulary words selected. CONCLUSION: The authors recommend further
      investigations of the collateral impacts of AAC on skills other than expressive
      language.

PMID- 23957299
TI  - 'We had to do what we thought was right at the time': retrospective discourse on
      the 2009 H1N1 pandemic in the UK.
AB  - For a few weeks in 2009 it was not certain whether the world faced a lethal
      influenza pandemic. As it turned out, the H1N1 pandemic was less severe than
      anticipated, though the infection did affect groups not usually susceptible to
      influenza. The deep uncertainties of this pandemic moment were associated with
      immense practical, scientific and political challenges for public health agencies
      around the world. We examine these challenges by drawing on the sociology of
      uncertainty to analyse the accounts given by UK public health practitioners who
      managed local responses to the pandemic. We discuss the retrospective and
      mitigating discourse; 'we had to do what we thought was right at the time', used
      by interviewees to explain their experience of articulating plans for a severe
      pandemic influenza with one that turned out to be mild. We explore the importance
      of influenza's history and imagined future for pandemic management and,
      relatedly, how pandemic response and control plans disrupted the normal ways in
      which public health exercises its authority. We conclude by suggesting that
      difficulties in the management of pandemic influenza lie in its particular
      articulation of precautions, that is, securing a safe future against that which
      cannot be predicted. 

PMID- 23957300
TI  - Low triiodothyronine: a pathway to coronary calcification in patients maintained
      on peritoneal dialysis.

PMID- 23957301
TI  - Antioxidant, alpha-glucosidase and xanthine oxidase inhibitory activity of
      bioactive compounds from maize (Zea mays L.).
AB  - Chemical investigations into maize (Zea mays L.) kernels yielded phenolic
      compounds, which were structurally established using chromatographic and
      spectroscopic methods. The isolated phenolic compounds from maize kernel were
      examined in vitro for their antioxidant abilities by DPPH (2,2-diphenyl-1-picryl
      hydrazine) radical, OH radical scavenging activity, and reducing ability, along
      with alpha-glucosidase and xanthine oxidase (XO) inhibition. The isolated maize
      phenolics revealed significant xanthine oxidase and alpha-glucosidase inhibitory
      activity to that of allopurinol and acarbose in vitro and in vivo, respectively.
      The kinetics study with xanthine oxidase revealed competitive type of inhibition
      by isolated maize vanillic acid (M2), ferulic acid (M5), 3'-methoxyhirsutrin
      (M7), and peonidin-3-glucoside (M10) as compared to control allopurinol. Overall,
      with few exceptions, all the phenolic compounds from maize kernel revealed
      significant biological activities with all parameters examined. Also, the
      phenolic compounds from maize were found to be more reactive toward DPPH radical
      and had considerable reducing ability and OH radical scavenging activity. These
      findings suggest that maize kernel phenolic compounds can be considered as
      potential antioxidant, alpha-glucosidase, and XO inhibitory agents those might be
      further explored for the design of lead antioxidant, antidiabetic and antigout
      drug candidates using in vivo trials. 

PMID- 23957302
TI  - Influence of the front part of the vehicle and cyclist's sitting position on the
      severity of head injury in side collision.
AB  - An injury of cyclists during a collision with a car is currently a neglected
      topic. Most research projects evaluate in detail the injury of pedestrians, but
      with an increasing number of cyclists it will be necessary to devote more
      attention to their safety. This study is focused on the most common type of
      collision and offers insights into the biomechanics of cyclist's head injury
      without the use of bicycle helmet. Initial mechanical and kinematic conditions
      that affect Head Injury Criterion (HIC) after a car hits a cyclist were
      determined using simulation software MADYMO. In relation to HIC, three different
      shapes of the front part of the car and three basic cyclist's positions were
      compared.

PMID- 23957303
TI  - Xylitol production by Cyberlindnera (Williopsis) saturnus, a tropical mangrove
      yeast from xylose and corn cob hydrolysate.
AB  - AIM: Potential for xylitol production from xylose and corn cob hydrolysate by a
      tropical mangrove yeast. METHODS AND RESULTS: In the present study, 21 fungi were
      isolated from detritus-based mangrove wetlands along the Indian west coast. Of
      these, one yeast isolate had the ability to grow and assimilate xylose producing
      significant amounts of xylitol (38.63 g l(-1) ). A maximum yield of 0.54 g g(-1)
      was obtained after 144 h of growth on xylose (150 g l(-1) ) and corn cob
      hydrolysate (CCH, containing 65 g l(-1) xylose). Using biochemical and molecular
      methods, the yeast was identified as Cyberlindnera (Williopsis) saturnus.
      Preliminary characterization of enzymes in the cell-free extract revealed that
      while xylose reductase (XR) preferred NADPH to NADH as cofactor, xylitol
      dehydrogenase (XDH) was NAD specific. CONCLUSIONS: Significant amounts of xylitol
      could be produced on CCH using C. saturnus isolated from tropical mangrove
      wetlands. The yeast has the potential to assimilate rather than ferment xylose as
      its XR has a preference for NADPH. SIGNIFICANCE AND IMPACT OF THE STUDY: Microbes
      offer an economically viable and green approach for production of xylitol, an
      industrially important compound. A mangrove ecosystem with its battery of
      lignocellulolytic enzymes is an ideal location for isolating fungi capable of
      producing xylitol from agroindustrial waste such as CCH.

PMID- 23957304
TI  - 'Reduced malignancy as a mechanism for longevity in mice with adenylyl cyclase
      type 5 disruption'.
AB  - Disruption of adenylyl cyclase type 5 (AC5) knockout (KO) is a novel model for
      longevity. Because malignancy is a major cause of death and reduced lifespan in
      mice, the goal of this investigation was to examine the role of AC5KO in
      protecting against cancer. There have been numerous discoveries in genetically
      engineered mice over the past several decades, but few have been translated to
      the bedside. One major reason is that it is difficult to alter a gene in
      patients, but rather a pharmacological approach is more appropriate. The current
      investigation employs a parallel construction to examine the extent to which
      inhibiting AC5, either in a genetic knockout (KO) or by a specific
      pharmacological inhibitor protects against cancer. This study is unique, not only
      because a combined genetic and pharmacological approach is rare, but also there
      are no prior studies on the extent to which AC5 affects cancer. We found that
      AC5KO delayed age-related tumor incidence significantly, as well as protecting
      against mammary tumor development in AC5KO * MMTV-HER-2 neu mice, and B16F10
      melanoma tumor growth, which can explain why AC5KO is a model of longevity. In
      addition, a Food and Drug Administration approved antiviral agent, adenine 9-beta
      D-arabinofuranoside (Vidarabine or AraAde), which specifically inhibits AC5,
      reduces LP07 lung and B16F10 melanoma tumor growth in syngeneic mice. Thus,
      inhibition of AC5 is a previously unreported mechanism for prevention of cancers
      associated with aging and that can be targeted by an available pharmacologic
      inhibitor, with potential consequent extension of lifespan. 

PMID- 23957305
TI  - Bioconjugation by native chemical tagging of C-H bonds.
AB  - A general C-H functionalization method for the tagging of natural products and
      pharmaceuticals is described. An azide-containing sulfinate reagent allows the
      appendage of azidoalkyl chains onto heteroaromatics, the product of which can
      then be attached to a monoclonal antibody by a "click" reaction. This strategy
      expands the breadth of bioactive small molecules that can be linked to
      macromolecules in a manner that is beyond the scope of existing methods in
      bioconjugation to permit tagging of the "seemingly untaggable". 

PMID- 23957307
TI  - A threatening face in the crowd: effects of emotional singletons on visual
      working memory.
AB  - Faces with threatening versus positive expressions are better remembered in
      visual working memory (WM) and are especially effective at capturing attention.
      We asked how the presence of a single threatening or happy face affects WM for
      concurrently viewed faces with neutral expressions. If threat captures attention
      and attention determines WM, then a WM performance cost for neutral faces should
      be evident. However, if threat boosts processing in an object-specific,
      noncompetitive manner, then no such costs should be produced. Participants viewed
      three neutral and one angry or happy face for 2 s. Face recognition was tested 1
      s later. Although WM was better for singletons than nonsingletons and better for
      angry versus happy singletons, WM for neutral faces remained unaffected by either
      singleton. These results, combined with eye movement and response time analyses,
      argue against a selective attention account of threat-based benefits to WM and
      support object-specific enhancement via threat processing.

PMID- 23957306
TI  - Depletion of the cellular antioxidant system contributes to tenofovir disoproxil
      fumarate - induced mitochondrial damage and increased oxido-nitrosative stress in
      the kidney.
AB  - BACKGROUND: Nephrotoxicity is a dose limiting side effect of tenofovir, a reverse
      transcriptase inhibitor that is used for the treatment of HIV infection. The
      mechanism of tenofovir nephrotoxicity is not clear. Tenofovir is specifically
      toxic to the proximal convoluted tubules and proximal tubular mitochondria are
      the targets of tenofovir cytotoxicity. Damaged mitochondria are major sources of
      reactive oxygen species and cellular damage is reported to occur after the
      antioxidants are depleted. The purpose of the study is to investigate the
      alterations in cellular antioxidant system in tenofovir induced renal damage
      using a rat model. RESULTS: Chronic tenofovir administration to adult Wistar rats
      resulted in proximal tubular damage (as evidenced by light microscopy), proximal
      tubular dysfunction (as shown by Fanconi syndrome and tubular proteinuria), and
      extensive proximal tubular mitochondrial injury (as revealed by electron
      microscopy). A 50% increase in protein carbonyl content was observed in the
      kidneys of TDF treated rats as compared with the control. Reduced glutathione was
      decreased by 50%. The activity of superoxide dismutase was decreased by 57%,
      glutathione peroxidase by 45%, and glutathione reductase by 150% as compared with
      control. Carbonic Anhydrase activity was decreased by 45% in the TDF treated rat
      kidneys as compared with control. Succinate dehydrogenase activity, an indicator
      of mitochondrial activity was decreased by 29% in the TDF treated rat kidneys as
      compared with controls, suggesting mitochondrial dysfunction. CONCLUSION:
      Tenofovir- induced mitochondrial damage and increased oxidative stress in the rat
      kidneys may be due to depletion of the antioxidant system particularly, the
      glutathione dependent system and MnSOD.

PMID- 23957308
TI  - Automatic imitation is reduced in narcissists.
AB  - Narcissism is a personality trait that has been extensively studied in normal
      populations. Individuals high on subclinical narcissism tend to display an
      excessive self-focus and reduced concern for others. Does their disregard of
      others have roots in low-level processes of social perception? We investigated
      whether narcissism is related to the automatic imitation of observed actions. In
      the automatic imitation task, participants make cued actions in the presence of
      action videos displaying congruent or incongruent actions. The difference in
      response times and accuracy between congruent and incongruent trials (i.e., the
      interference effect) is a behavioral index of motor resonance in the brain-a
      process whereby observed actions activate matching motor representations in the
      observer. We found narcissism to be negatively related to interference in the
      automatic imitation task, such that high narcissism is associated with reduced
      imitation. Thus, levels of narcissism predict differences in the tendency to
      automatically resonate with others, and the pattern of data we observe suggests
      that a key difference is that high narcissists possess an improved ability to
      suppress automatic imitation when such imitation would be detrimental to task
      performance. To the extent that motor resonance is a product of a human mirror
      system, our data constitute evidence for a link between narcissistic tendencies
      and mirror system functioning.

PMID- 23957309
TI  - Short-term visual deprivation improves the perception of harmonicity.
AB  - Neuroimaging studies have shown that the perception of auditory stimuli involves
      occipital cortical regions traditionally associated with visual processing, even
      in the absence of any overt visual component to the task. Analogous behavioral
      evidence of an interaction between visual and auditory processing during purely
      auditory tasks comes from studies of short-term visual deprivation on the
      perception of auditory cues, however, the results of such studies remain
      equivocal. Although some data have suggested that visual deprivation
      significantly increases loudness and pitch discrimination and reduces spatial
      localization inaccuracies, it is still unclear whether such improvement extends
      to the perception of spectrally complex cues, such as those involved in speech
      and music perception. We present data demonstrating that a 90-min period of
      visual deprivation causes a transient improvement in the perception of
      harmonicity: a spectrally complex cue that plays a key role in music and speech
      perception. The results provide clear behavioral evidence supporting a role for
      the visual system in the processing of complex auditory stimuli, even in the
      absence of any visual component to the task.

PMID- 23957311
TI  - Revised basin-hopping Monte Carlo algorithm for structure optimization of
      clusters and nanoparticles.
AB  - Suggestions for improving the Basin-Hopping Monte Carlo (BHMC) algorithm for
      unbiased global optimization of clusters and nanoparticles are presented. The
      traditional basin-hopping exploration scheme with Monte Carlo sampling is
      improved by bringing together novel strategies and techniques employed in
      different global optimization methods, however, with the care of keeping the
      underlying algorithm of BHMC unchanged. The improvements include a total of
      eleven local and nonlocal trial operators tailored for clusters and nanoparticles
      that allow an efficient exploration of the potential energy surface, two
      different strategies (static and dynamic) of operator selection, and a filter
      operator to handle unphysical solutions. In order to assess the efficiency of our
      strategies, we applied our implementation to several classes of systems,
      including Lennard-Jones and Sutton-Chen clusters with up to 147 and 148 atoms,
      respectively, a set of Lennard-Jones nanoparticles with sizes ranging from 200 to
      1500 atoms, binary Lennard-Jones clusters with up to 100 atoms, (AgPd)55 alloy
      clusters described by the Sutton-Chen potential, and aluminum clusters with up to
      30 atoms described within the density functional theory framework. Using unbiased
      global search our implementation was able to reproduce successfully the great
      majority of all published results for the systems considered and in many cases
      with more efficiency than the standard BHMC. We were also able to locate
      previously unknown global minimum structures for some of the systems considered.
      This revised BHMC method is a valuable tool for aiding theoretical investigations
      leading to a better understanding of atomic structures of clusters and
      nanoparticles. 

PMID- 23957310
TI  - Can costs of screening for hypertension and diabetes in dental care and follow-up
      in primary health care be predicted?
AB  - AIM: The purpose was to assess the direct costs of screening for high blood
      pressure and blood glucose in dental care and of follow-up in primary health care
      and, based on these data, arrive at a prediction function. Study population. All
      subjects coming for routine check-ups at three dental health clinics were invited
      to have blood pressure or blood glucose measurements; 1,623 agreed to
      participate. Subjects screening positive were referred to their primary health
      care centres for follow-up. METHODS: Information on individual screening time was
      registered during the screening process, and information on accountable time,
      costs for the screening staff, overhead costs, and analysis costs for the
      screening was obtained from the participating dental clinics. The corresponding
      items in primary care, i.e. consultation time, number of follow-up appointments,
      accountable time, costs for the follow-up staff, overhead costs, and analysis
      costs during follow-up were obtained from the primary health care centres.
      RESULTS: The total screening costs per screened subject ranged from ?7.4 to ?9.2
      depending on subgroups, corresponding to 16.7-42.7 staff minutes. The
      corresponding follow-up costs were ?57-?91. The total resource used for screening
      and follow-up per diagnosis was 563-3,137 staff minutes. There was a strong
      relationship between resource use and numbers needed to screen (NNS) to find one
      diagnosis (P < 0.0001, degree of explanation 99%). CONCLUSIONS: Screening and
      follow-up costs were moderate and appear to be lower for combined screening of
      blood pressure and blood glucose than for separate screening. There was a strong
      relationship between resource use and NNS.

PMID- 23957312
TI  - Reproductive ecology and genetic variability in natural populations of the wild
      potato, Solanum kurtzianum.
AB  - The cultivated potato (Solanum tuberosum ssp. tuberosum) has more than 200
      related wild species distributed along the Andes, adapted to a wide range of
      geographical and ecological areas. Since the last century, several collection
      expeditions were carried out to incorporate genetic variability into the potato
      germplasm around the world. However, little is known about the reproductive
      ecology and genetic population structure of natural potato population from field
      studies. The aim of this work is to study, in the field, the genetic variability
      and reproductive strategies of populations of one of the most widely distributed
      potato species in Argentina, Solanum kurtzianum, growing in Mendoza province.
      AFLP markers showed that the genetic variability is mainly present among plants
      within populations, indicating that in the sampled populations, sexual
      reproduction is more relevant than clonal multiplication (by tubers). Additional
      evidence was obtained evaluating the genetic diversity in populations with a
      distribution in patches, where several genotypes were always detected. From a
      field study performed in the Villavicencio Natural Reserve, we found that the
      average number of plump seeds per fruit was 94.3, identified and calculated the
      foraging distance of four insect pollinators, and demonstrated the seed dispersal
      by storm water channels. We argue that the breeding system, the two modes of
      reproduction and the ecological interaction described here may have a prominent
      role in determining the genetic structure of S. kurtzianum populations, and
      discuss the importance of field studies on population genetics, reproductive
      biology and ecology to design collections and conservation strategies. 

PMID- 23957313
TI  - Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF)
      normative elevation rates: comparisons with epidemiological prevalence rates.
AB  - Odland, Berthelson, Sharma, Martin, and Mittenberg ( 2013 ) caution that
      clinically elevated scale scores produced by members of the Minnesota Multiphasic
      Personality Inventory-2-Restructured Form (MMPI-2-RF; Ben-Porath & Tellegen, 2008
      /2011) normative sample raise concerns about the potential for false positive
      findings of psychopathology. However, the MMPI-2-RF normative sample is intended
      to represent the general population of the United States, 26.2% of which met
      criteria for a Diagnostic and Statistical Manual-IV (APA, 1994 ) disorder in a 12
      month period (Kessler, Chiu, Demler, & Walters, 2005 ). In the current study we
      compare scale elevation rates in the MMPI-2-RF normative sample to prevalence
      rates of mental disorders primarily drawn from the National Comorbidity Study
      Replication (Kessler et al., 2005 ). Our objective was to evaluate MMPI-2-RF
      elevation rates in an epidemiological context. Results indicate that MMPI-2-RF
      scale elevation rates were generally consistent with epidemiological data when
      examined in the context of standard interpretation guidelines for the inventory.
      We also reiterate Ben-Porath and Tellegen's (2008/2011) caution that MMPI-2-RF
      scale elevations alone are not sufficient to indicate the presence of psychiatric
      disorder. Rather they are best viewed as indications of the need to evaluate the
      individual for possible disorder(s). Implications of these results, limitations
      of this study, and future directions in research are discussed. 

PMID- 23957314
TI  - Genomic integrity of the Y chromosome sequence-tagged-sites in infertile and Down
      syndrome Jordanian males.
AB  - The long arm of the Y chromosome contains nonoverlapping regions termed
      azoospermia factor (AZF) with great influence on male fertility. Microdeletions
      at these regions minimise the males' ability to father offsprings. In this
      preliminary study, we attempted to screen the presence or absence of twenty Y
      chromosome's sequence-tagged sites (STS) associated with fertility in infertile
      and Down syndrome (DS) males. Genomic DNA from 35 fertile, 74 infertile and 22
      karyotyped DS males was extracted and amplified in multiplex polymerase chain
      reaction (PCR) containing 20 primer pairs that amplify Y-specific STS that cover
      functional regions associated with AZF and spermatogenesis-related genes. Our
      results indicated the integrity of the Y chromosome at the 20 fertility markers
      for both the fertile and Down syndrome males. However, the results of the
      infertile males showed the presence of microdeletions at these Y-specific STS.
      Three samples showed Y chromosome microdeletion when blood and seminal fluid
      genomic DNA were assayed, while two samples showed microdeletion only when
      seminal fluid genomic DNA was assayed. The current study demonstrated that the
      molecular genetic aspect of infertility should be given proper attention when
      dealing with infertility cases. Furthermore, our results indicate the importance
      of genetic counselling in managing infertility cases.

PMID- 23957316
TI  - Foraging strategy of a neotropical primate: how intrinsic and extrinsic factors
      influence destination and residence time.
AB  - Most animals need to actively search for food to meet energetic requirements and
      live in heterogeneous environments where food resources have complex spatio
      temporal patterns of availability. Consequently, foraging animals need to find a
      balance between effort and resource allocation while accounting for intrinsic and
      extrinsic factors, which are often overlooked when modelling foraging behaviour.
      We identified the decision rules for foraging in black howler monkeys (Alouatta
      pigra), according to food preferences, locations of high-quality patches and
      previously eaten trees, phenology of food resources and hunger state. We depicted
      foraging in two stages: (i) the choice of the immediate next tree and (ii) the
      time spent on this tree. We used a recently developed model for inference of
      movement processes, incorporating resource selection functions into a Markov
      chain framework. We found that monkeys tend to move to preferred tree species at
      each step. However, we did not find conclusively that, at each step, monkeys
      direct their movements to reach high-quality patches. In fact, they were using
      these patches intensively, thus limiting the possibility to move towards other
      high-quality patches. Time spent on a tree was positively and strongly affected
      by the presence of preferred food items, but not by its species. We also showed
      that time spent on trees increased as a function of satiation state. We suggest
      that the strategy adopted by black howlers tends to be efficient because choosing
      preferred trees at each step and spending spend more time where preferred
      resources are available should favour energy intake and restrain movement costs.
      This study showcases a modelling framework that can be widely used in ecology to
      describe movements as a combination of multiple attraction and repulsion sources,
      such as mates and competitors.

PMID- 23957317
TI  - A comparison of the efficacy of test-driven learning versus self-assessment
      learning.
AB  - Objective : We compared self-assessment and test-driven learning in two groups of
      students who studied the same subject. Methods : This was a randomized
      comparative experimental study. The subjects were 259 first-quarter students who
      were divided into a test group and a self-assessment group based on the methods
      they used for their learning assessments. We measured the scores and difficulty
      levels of 3 formal written exams. Students' attitudes toward self-assessment or
      test-driven learning were surveyed. Results : The mean scores of exam 1, exam 2,
      and a summative exam were 34 (+/-6), 32 (+/-8), and 44 (+/-6) for the self
      assessment group, respectively, with corresponding scores of 33 (+/-6), 33 (+/
      7), 43 (+/-6) for the test group. There were no significant differences in the
      mean scores on all 3 tests between the two groups (p > .05). Of the students in
      the self-assessment group, 64% scored at least 90%, whereas 47% of students in
      the test group answered at least 90% of the questions correctly (p < .001). For
      the survey, students expressed a positive attitude toward both learning
      strategies. Conclusion : Both self-assessment and tests could have a significant
      impact on students' learning, but each offers different strengths and weaknesses.

PMID- 23957315
TI  - Targeting Cdc42 in cancer.
AB  - INTRODUCTION: The Rho GTPases are a family of proteins that control fundamental
      cellular processes in response to extracellular stimuli and internal programs.
      Rho GTPases function as molecular switches in which the GTP-bound proteins are
      active and GDP-bound proteins are inactive. This article will focus on one Rho
      family member, Cdc42, which is overexpressed in a number of human cancers, and
      which might provide new therapeutic targets in malignancies. AREAS COVERED: In
      this article, the key regulators and effectors of Cdc42 and their molecular
      alterations are described. The complex interactions between the signaling
      cascades regulated by Cdc42 are also analyzed. EXPERT OPINION: While mutations in
      Cdc42 have not been reported in human cancer, aberrant expression of Cdc42 has
      been reported in a variety of tumor types and in some instances has been
      correlated with poor prognosis. Recently, it has been shown that Cdc42 activation
      by oncogenic Ras is crucial for Ras-mediated tumorigenesis, suggesting that
      targeting Cdc42 or its effectors might be useful in tumors harboring activating
      Ras mutations.

PMID- 23957318
TI  - Prevalence of nonmusculoskeletal versus musculoskeletal cases in a chiropractic
      student clinic.
AB  - Objective : We sought to identify the percentage of nonmusculoskeletal and
      musculoskeletal conditions treated by interns in the National University of
      Health Sciences (NUHS) Student Clinic compared to chiropractic and allopathic
      health care professionals. Methods : The information gathered was taken from the
      charts of patients treated in the fall trimester, dated September 12, 2011
      through December 9, 2011. The data collected included ICD-9 codes for the
      conditions treated, the number of patient visits, age, and gender, and was
      evaluated using Microsoft Excel. Results : Over half of the 113 eligible patients
      were women with a mean patient age of 28 years, an average of three treated
      diagnoses, and a mean of seven treatments. Those treated only for musculoskeletal
      conditions totaled 52% of the patients; 48% of the patients were treated for
      nonmusculoskeletal conditions, or musculoskeletal plus nonmusculoskeletal
      conditions. Conclusion : The NUHS Student Clinic interns are treating a greater
      percentage of nonmusculoskeletal conditions and a lesser percentage of
      musculoskeletal conditions than practicing chiropractic physicians. The student
      interns also treat a lesser percentage of nonmusculoskeletal and a greater
      percentage of musculoskeletal conditions than allopathic practitioners. This
      comparison would suggest that NUHS is nearing its institutional goal of training
      its student interns as primary care practitioners.

PMID- 23957319
TI  - Stress in chiropractic education: a student survey of a five-year course.
AB  - Objective : Stress encompasses academic issues, such as time management,
      increased work load, and new subject matter, but cannot be separated from
      stressors, such as social adjustment and financial pressure. Our study
      investigated whether perceived level of academic or practical attainment and the
      method of study were associated with the amount of perceived stress during
      students" studies. Methods : A semi-structured self-administered questionnaire
      was piloted and distributed to 134 students at a chiropractic college at the end
      of a lecture. Results : The survey had a response rate of 81%. Students in their
      fourth year consistently reported the highest perceived levels of stress, with
      81% feeling that their ability to study was affected by their financial situation
      and 56% felt overwhelmed at their ability to cope with their college workload.
      All year groups were stressed during their course of studies, but the stressor
      varies depending on the year of study. Conclusions : Year 4 consistently
      demonstrated the highest levels of stress. All students, regardless of year
      group, experienced varying degrees of stress while studying and the central
      stressor changed depending on the time position within the course. 

PMID- 23957321
TI  - Using computer-assisted learning to engage diverse learning styles in
      understanding business management principles.
AB  - Objective : Changes in small business and insurance present challenges for newly
      graduated chiropractors. Technology that reaches identified, diverse learning
      styles may assist the chiropractic student in business classes to meet course
      outcomes better. Thus, the purpose of our study is to determine if the use of
      technology-based instructional aids enhance students' mastery of course learning
      outcomes. Methods : Using convenience sampling, 86 students completed a survey
      assessing course learning outcomes, learning style, and the helpfulness of
      lecture and computer-assisted learning related to content mastery. Quantitative
      analyses occurred. Results : Although respondents reported not finding the
      computer-assisted learning as helpful as the lecture, significant relationships
      were found between pre- and post-assisted learning measures of the learning
      outcomes 1 and 2 for the visual and kinesthetic groups. Surprisingly, however,
      all learning style groups exhibited significant pre- and post-assisted learning
      appraisal relationships with learning outcomes 3 and 4. Conclusion : While
      evidence exists within the current study of a relationship between students'
      learning of the course content corollary to the use of technologic instructional
      aids, the exact nature of the relationship remains unclear.

PMID- 23957320
TI  - Knowledge of accurate blood pressure measurement procedures in chiropractic
      students.
AB  - Objective : Blood pressure measurement is a basic clinical procedure. However,
      studies have shown that many errors are made when health care providers acquire
      blood pressure readings. Our study assessed knowledge of blood pressure
      measurement procedures in chiropractic students. Methods : This was an
      observational, descriptive study. A questionnaire based on one created by the
      American Heart Association was given to 1st, 2nd, 3rd, and final year students (n
      = 186). A one way ANOVA was used to analyze the data. Results : Of the students
      80% were confident that their knowledge of this clinical skill was adequate or
      better. However, the overall score on the knowledge test of blood pressure-taking
      skills was 52% (range, 24%-88%). The only significant difference in the mean
      scores was between the 1st and 2nd year students compared to the 3rd and 4th year
      students (p < .005). Of the 16 questions given, the following mean scores were:
      1st year 10.45, 2nd year 9.75, 3rd year 7.93, and 4th year 8.33. Of the 16 areas
      tested, 10 were of major concern (test item score <70%), showing the need for
      frequent retraining of chiropractic students. Conclusion : Consistent with
      studies in other health care disciplines, our research found the knowledge of
      blood pressure skills to be deficient in our sample. There is a need for
      subsequent training in our teaching program. 

PMID- 23957322
TI  - Feasibility of using a standardized patient encounter for training chiropractic
      students in tobacco cessation counseling.
AB  - Objective : Although tobacco cessation training is included in many health
      profession programs, it is not yet routinely incorporated into chiropractic
      education. The purpose of this study was to assess the feasibility of
      incorporating a problem-based learning tobacco cessation activity into a lecture
      course for chiropractic students. Methods : Seventy-two students were assigned to
      participate in two 1-hour lectures on health promotion counseling and tobacco
      cessation followed by an experiential student-driven lab session using
      standardized patients at various stages of dependency and willingness to quit.
      The intervention was based on the transtheoretic model and the "5 A's" of
      counseling (ask, advise, assess, assist, arrange). Outcomes were assessed via (1)
      questionnaires completed by the standardized patients regarding the students' use
      of the 5A's, and (2) questionnaires completed by the students using a 5-point
      Likert scale of "strongly disagree" to "strongly agree" on the acceptability of
      this method of learning. Descriptive statistics were computed. Results : Sixty
      eight students (94%) completed the activity, spending a median of 2.5 minutes
      with patients. Over 90% addressed 4 of the 5A's: 99% asked patients if they were
      smokers; 97% advised them to quit; 90% assessed if they were willing to quit; and
      99% offered assistance in quitting. Only 79% arranged a follow-up visit. Overall,
      students expressed a positive response to the experience; 81% said it increased
      their confidence in being able to advise patients, and 77% felt it would be
      valuable for use in their future practice. Conclusion : This active learning
      exercise appeared to be a feasible way to introduce tobacco counseling into the
      curriculum. 

PMID- 23957323
TI  - An investigation into the demographics and motivations of students studying for a
      chiropractic degree.
AB  - Objective : This research aimed to investigate motivations for studying
      chiropractic, and to determine what students look for in a course/college and
      potential barriers to studying chiropractic. Methods : The study design was a
      cross-sectional survey. Following IRB/Ethical approval, a paper-based
      questionnaire was distributed to students at McTimoney College of Chiropractic.
      Demographic data were compared to another chiropractic college in the United
      Kingdom. Results : The questionnaire response rate was 70.8% (n = 121).
      Motivating factors for studying chiropractic included a desire to help others
      (54.5%, n = 66), with 44.6% (n = 54) attracted by chiropractic's holistic,
      drugless approach to health. Previous help from chiropractic influenced 55.4% (n
      = 67) and 22.3% (n = 27) felt chiropractic had "changed their life." Just over
      half of the respondents (55.4%, n = 67) viewed the ability to work while studying
      as extremely important and 73.6% (n = 89) said they could not have studied
      chiropractic without this. Conclusion : Previous help from chiropractic care was
      a common motivation for studying chiropractic. The ability to work while studying
      was seen as vital by many students and, without it, the vast majority felt they
      could not have studied chiropractic. 

PMID- 23957324
TI  - Video capture on student-owned mobile devices to facilitate psychomotor skills
      acquisition: A feasibility study.
AB  - Objective : We evaluated the feasibility of using mobile device technology to
      allow students to record their own psychomotor skills so that these recordings
      can be used for self-reflection and formative evaluation. Methods : Students were
      given the choice of using DVD recorders, zip drive video capture equipment, or
      their personal mobile phone, device, or digital camera to record specific
      psychomotor skills. During the last week of the term, they were asked to complete
      a 9-question survey regarding their recording experience, including details of
      mobile phone ownership, technology preferences, technical difficulties, and
      satisfaction with the recording experience and video critique process. Results :
      Of those completing the survey, 83% currently owned a mobile phone with video
      capability. Of the mobile phone owners 62% reported having email capability on
      their phone and that they could transfer their video recording successfully to
      their computer, making it available for upload to the learning management system.
      Viewing the video recording of the psychomotor skill was valuable to 88% of
      respondents. Conclusions : Our results suggest that mobile phones are a viable
      technology to use for the video capture and critique of psychomotor skills, as
      most students own this technology and their satisfaction with this method is
      high. 

PMID- 23957325
TI  - Antifungal efficacy of lasers against dermatophytes and yeasts in vitro.
AB  - PURPOSE: Approximately 2-13% of the world population suffers from onychomycosis.
      Recently, lasers have been introduced for treatment. However, no effect was found
      with in vitro laser irradiation of pathogens on agar plates. This study aimed to
      investigate the efficacy of laser irradiation against fungi using an alternative
      in vitro approach. MATERIALS AND METHODS: Lasers of 808, 980 and 1064 nm were
      used to heat cell culture media and a nail clipping. Trichophyton rubrum. T.
      interdigitale. Microsporum gypseum. Candida albicans. C. parapsilosis, and C.
      guilliermondii species were subcultured and subjected to laser treatments
      (808/980 nm: 9-27 J/cm(2), 6 ms, 12 * 12 or 12 * 50 mm and 1064 nm: 50-240
      J/cm(2), 90 ms, 5-10 mm). After irradiation, the fungal elements were transferred
      onto agar plates using conventional and Drigalski spatulas and were incubated for
      6 days. RESULTS: The highest increase in temperature was found using a 980-nm
      laser with a pulse duration of 6 ms and a fluence of 27 J/cm(2). The histology
      work-up revealed a dissection of the nail plate from the nail bed tissue after
      laser irradiation. Growth inhibition was only found for C. guilliermondii and T.
      interdigitale. All other pathogens presented only reduced growth, and C. albicans
      growth was unaffected. CONCLUSIONS: This study demonstrates a clear thermal
      effect for linear scanning 980-nm and long-pulsed 1064-nm laser systems on either
      nail clippings or cell culture media. Complete pathogen growth impairment was
      achieved if temperatures were measured above 50  degrees C. The results for the
      1064-nm system were almost comparable to 980 nm results.

PMID- 23957326
TI  - A method to convert MRI images of temperature change into images of absolute
      temperature in solid tumours.
AB  - PURPOSE: During hyperthermia (HT), the therapeutic response of tumours varies
      substantially within the target temperature range (39-43  degrees C). Current
      thermometry methods are either invasive or measure only temperature change, which
      limits the ability to study tissue responses to HT. This study combines manganese
      containing low temperature sensitive liposomes (Mn-LTSL) with proton resonance
      frequency shift (PRFS) thermometry to measure absolute temperature in tumours
      with high spatial and temporal resolution using MRI. METHODS: Liposomes were
      loaded with 300 mM MnSO(4). The phase transition temperature (T(m)) of Mn-LTSL
      samples was measured by differential scanning calorimetry (DSC). The release of
      manganese from Mn-LTSL in saline was characterised with inductively coupled
      plasma atomic emission spectroscopy. A 2T GE small animal scanner was used to
      acquire dynamic T1-weighted images and temperature change images of Mn-LTSL in
      saline phantoms and fibrosarcoma-bearing Fisher-344 rats receiving hyperthermia
      after Mn-LTSL injection. RESULTS: The T(m) of Mn-LTSL in rat blood was 42.9 +/-
      0.2  degrees C (DSC). For Mn-LTSL samples (0.06 mM-0.5 mM Mn(2+) in saline)
      heated monotonically from 30  degrees C to 50  degrees C, a peak in the rate of
      MRI signal enhancement occurred at 43.1 degrees  +/- 0.3  degrees C. The same
      peak in signal enhancement rate was observed during heating of fibrosarcoma
      tumours (N = 3) after injection of Mn-LTSL, and the peak was used to convert
      temperature change images into absolute temperature. Accuracies of calibrated
      temperature measurements were in the range 0.9-1.8  degrees C. CONCLUSION: The
      release of Mn(2+) from Mn-LTSL affects the rate of MR signal enhancement which
      enables conversion of MRI-based temperature change images to absolute
      temperature.

PMID- 23957328
TI  - Ultrafine particles: exposure and source apportionment in 56 Danish homes.
AB  - Particle number (PN) concentrations (10-300 nm in size) were continuously
      measured over a period of ~45 h in 56 residences of nonsmokers in Copenhagen,
      Denmark. The highest concentrations were measured when occupants were present and
      awake (geometric mean, GM: 22.3 * 10(3) cm(-3)), the lowest when the homes were
      vacant (GM: 6.1 * 10(3) cm(-3)) or the occupants were asleep (GM: 5.1 * 10(3) cm(
      3)). Diary entries regarding occupancy and particle related activities were used
      to identify source events and apportion the daily integrated exposure among
      sources. Source events clearly resulted in increased PN concentrations and
      decreased average particle diameter. For a given event, elevated particle
      concentrations persisted for several hours after the emission of fresh particles
      ceased. The residential daily integrated PN exposure in the 56 homes ranged
      between 37 * 10(3) and 6.0 * 10(6) particles per cm(3).h/day (GM: 3.3 * 10(5) cm(
      3).h/day). On average, ~90% of this exposure occurred outside of the period from
      midnight to 6 a.m. Source events, especially candle burning, cooking, toasting,
      and unknown activities, were responsible on average for ~65% of the residential
      integrated exposure (51% without the unknown activities). Candle burning occurred
      in half of the homes where, on average, it was responsible for almost 60% of the
      integrated exposure.

PMID- 23957327
TI  - A cohort study of Chlamydia trachomatis treatment failure in women: a study
      protocol.
AB  - BACKGROUND: Chlamydia trachomatis is the most commonly diagnosed bacterial
      sexually transmitted infection in the developed world and diagnosis rates have
      increased dramatically over the last decade. Repeat infections of chlamydia are
      very common and may represent re-infection from an untreated partner or treatment
      failure. The aim of this cohort study is to estimate the proportion of women
      infected with chlamydia who experience treatment failure after treatment with 1
      gram azithromycin. METHODS/DESIGN: This cohort study will follow women diagnosed
      with chlamydia for up to 56 days post treatment. Women will provide weekly
      genital specimens for further assay. The primary outcome is the proportion of
      women who are classified as having treatment failure 28, 42 or 56 days after
      recruitment. Comprehensive sexual behavior data collection and the detection of Y
      chromosome DNA and high discriminatory chlamydial genotyping will be used to
      differentiate between chlamydia re-infection and treatment failure. Azithromycin
      levels in high-vaginal specimens will be measured using a validated liquid
      chromatography-tandem mass spectrometry method to assess whether poor
      azithromycin absorption could be a cause of treatment failure. Chlamydia culture
      and minimal inhibitory concentrations will be performed to further characterize
      the chlamydia infections. DISCUSSION: Distinguishing between treatment failure
      and re-infection is important in order to refine treatment recommendations and
      focus infection control mechanisms. If a large proportion of repeat chlamydia
      infections are due to antibiotic treatment failure, then international
      recommendations on chlamydia treatment may need to be re-evaluated. If most are
      re-infections, then strategies to expedite partner treatment are necessary.

PMID- 23957329
TI  - Therapeutic effectiveness of sustained low-efficiency hemodialysis plus
      hemoperfusion and continuous hemofiltration plus hemoperfusion for acute severe
      organophosphate poisoning.
AB  - There is no report on the effects of sustained low-efficiency dialysis (SLED)
      plus hemoperfusion (HP) (SLED + HP) in patients with acute severe organophosphate
      (OP) poisoning (ASOPP). This study was designed to compare the therapeutic
      effectiveness between SLED + HP and continuous hemofiltration (CHF) plus HP (CHF
      + HP) in patients with ASOPP. In order to assess the two treatment methods, 56
      patients with ASOPP were divided into CHF + HP group and SLED + HP group. The
      biochemical indicators, in-hospital duration, hemodynamic parameters, Acute
      Physiology, and Chronic Health Evaluation (APACHE II) score, and survival and
      mortality rates were compared. In both groups after treatment, the levels of
      serum creatine kinase isozyme MB, creatine kinase, creatinine, glutamic
      oxalacetic transaminease, and glutamate-pyruvate transaminase, and the APACHE II
      scores on the first, second, and seventh day decreased (P < 0.05), whereas the
      levels of serum acetylcholinesterase increased. The two groups showed no
      statistical differences in in-hospital duration, biochemical indicators, APACHE
      II score, hemodynamic parameters, survival rate, or the mortality rate (P >
      0.05). In conclusion, SLED has similar hemodynamic stability to CHF and the two
      treatment methods have similar effects on ASOPP patients. More importantly, SLED
      plus HP is relatively economical and convenient for patients with ASOPP in
      clinical practice. 

PMID- 23957330
TI  - Structure-activity relationships of new 1-substitutedmethyl-4-[5-(N-methyl-N
      propylamino)pentyloxy]piperidines and selected 1-[(N-substituted-N-methyl)-3
      propyloxy]-5-(N-methy-l-N-propyl)-pentanediamines as H3 -antagonists.
AB  - Novel, potent non-imidazole histamine H3 receptor antagonists have been prepared
      and in vitro tested as H3 -receptor antagonists (the electrically evoked
      contraction of the guinea-pig jejunum). The present compounds contain a 4
      hydroxypiperidine core, which behaves as a conformationally restricted version of
      the 3-amino-1-propanol moiety common to the many previously described non
      imidazole H3 ligands. Detailed structure-activity studies revealed that 1-(2
      benzofuranylmethyl)- 5c (pA2 = 8.47 +/- 0.05) and 1-(3-benzofuranylmethyl)-4-[5
      (N-methyl-N-propyl)pentyloxy]piperidine 5d (pA2 = 8.15 +/- 0.07) exhibit high
      potency for the H3 histamine receptor. In addition, the potency of selected 1-[(N
      substituted-N-methyl)-3-propyloxy]-5-(N-methyl-N-propyl)pentanediamines as
      antagonist of the H3 histamine receptor was also evaluated. Replacement of the 4
      hydroxypiperidine of the leads 7 and 5c by a highly flexible 3
      (methylamino)propyloxy chain yields compounds 6a (pA2 = 8.02) and 6b (pA2 = 6.23)
      with higher and lower potency than their piperidine analogues (7, pA2 = 7.79; 5c,
      pA2 = 8.47), respectively. The histaminergic H1 antagonism of selected compounds
      5c, 5d and 6a has been established on the isolated guinea-pig ileum by
      conventional methods; the pA2 values have compared with the potency of
      pyrilamine. None of them showed any H1 -antagonistic activity (pA2 < 4; for
      pyrilamine pA2 = 8.5).

PMID- 23957331
TI  - Differences in V1 and V2 ski skating techniques described by accelerometers.
AB  - The aims of the study were to describe the differences between the ski skating
      techniques V1 and V2 and evaluate reproducibility in complex cyclic hip movements
      measured by accelerometers. Fourteen elite senior male cross-country skiers
      rollerskied twice for 1 min (V1 and V2) at 4 degrees  inclination and 3 m/s.
      Tests were repeated after 20 min and again 4 months later. Five triaxial
      accelerometers were attached to the subject's hip (os sacrum), poles, and ski
      boots. Post-processing included transforming to an approximately global
      coordinate system, normalization for cycle time, double integration for
      displacement, and revealing temporal patterns. Different acceleration patterns
      between techniques and large correlation coefficients (Pearson's r = 0.6-0.9)
      between repeated trials were seen for most parameters. In V2, the hip was lowered
      [-10.9 (1.2) cm], whereas in V1, the hip was elevated [4.8 (1.5) cm] during the
      pole thrust. In conclusion, V2 but not V1 showed similarities to double poling in
      the way that potential energy is gained between poling strokes and transferred to
      propulsion during the poling action. Elite skiers reproduce their own individual
      patterns. One triaxial accelerometer on the lower back can distinguish techniques
      and might be useful in field research as well as in providing individual feedback
      on daily technique training. 

PMID- 23957332
TI  - A conversation with Leonard and Leonore Herzenberg.
AB  - Leonard and Leonore Herzenberg have left an indelible mark on the fields of
      immunology and cell biology, both in research and clinical aspects. They are
      perhaps best known for developing the technologies of fluorescence flow cytometry
      and hybridomas. Over six decades, they made a number of important and fundamental
      discoveries in lymphocyte biology by applying these technologies. During this
      era, they immersed themselves in the sociopolitical environment, interjecting
      scientific rationale into public discourse about McCarthyism, nuclear fallout,
      war, genetics, and other politically charged topics. Their unique philosophy has
      shaped their lives, their science, and ultimately the scientific community. In
      this Conversation, we explore some of these driving forces and the impact on the
      laboratory. 

PMID- 23957334
TI  - Probiotics and primary prevention of atopic disease: are we closer to a firm
      evidence base for clinical use?

PMID- 23957336
TI  - Sputum cytokine mapping reveals an 'IL-5, IL-17A, IL-25-high' pattern associated
      with poorly controlled asthma.
AB  - BACKGROUND AND OBJECTIVE: Asthma is a heterogeneous disease with various
      clinical, inflammatory and molecular phenotypes. We studied sputum cytokine mRNA
      expression patterns in an unselected group of adult asthma patients to
      characterize the underlying inflammatory process. METHODS: Differential cell
      counts and cytokine mRNA (quantified by real-time PCR) were analysed on sputum
      from 40 controls and 66 asthmatic adults. A 'cytokine-high' profile was defined
      if mRNA levels for that particular cytokine exceeded the 90th percentile value in
      the control population. Radar graphs were used to visualize cytokine profiles.
      RESULTS: Sputum mRNA analysis confirmed heterogeneity of cytokine patterns among
      patients. Thirty-six patients (55%) had a Th2 cytokine pattern: 'IL-5-high' (n =
      13), 'IL-4-high' (n = 17) or 'IL-4- and IL-5-high' (n = 6). The 'IL-5-high'
      asthma profile (n = 13) coincided with the 'IL-25-high' (10/13) and surprisingly
      also with the 'IL-17A-high' (11/13) profile. The 'IL-5-/IL-25-/IL-17A-high
      profile was different from the 'IL-4-high' pattern. Patients with the 'IL-5, IL
      17A, IL-25-high' pattern had significantly worse lung function parameters.
      Uncontrolled asthmatics [Asthma Control Test (ACT) < 20] had higher sputum IL-5,
      IL-17A and IL-25 mRNA levels compared to controlled asthmatics (P = 0.002; P =
      0.002; P = 0.066) and uncontrolled asthma is more common among 'IL-5- and IL-17A
      high' asthmatics compared to 'IL-5-, IL-17A-low' asthmatics (chi(2) = 3.7, P =
      0.027; relative risk (RR): 1.8, 95% CI = 1.1-3.1). CONCLUSIONS AND CLINICAL
      RELEVANCE: Patients with the 'IL-5, IL-17A, IL-25-high' airway inflammatory
      pattern are often uncontrolled asthmatics, despite daily treatment. It seems
      worthwhile to evaluate whether measuring sputum cytokine levels might be used to
      assess the response to increased doses of steroids in patients with asthma.

PMID- 23957335
TI  - Perceived triggers of asthma: key to symptom perception and management.
AB  - Adequate asthma management depends on an accurate identification of asthma
      triggers. A review of the literature on trigger perception in asthma shows that
      individuals vary in their perception of asthma triggers and that the correlation
      between self-reported asthma triggers and allergy tests is only modest. In this
      article, we provide an overview of psychological mechanisms involved in the
      process of asthma triggers identification. We identify sources of errors in
      trigger identification and targets for behavioural interventions that aim to
      improve the accuracy of asthma trigger identification and thereby enhance asthma
      control. 

PMID- 23957337
TI  - Increased IL-17A secreting CD4+ T cells, serum IL-17 levels and exhaled nitric
      oxide are correlated with childhood asthma severity.
AB  - BACKGROUND: Measuring fractional exhaled nitric oxide (FeNO) is a simple and non
      invasive method for assessing airway inflammation. IL-17 plays an important role
      in T cell-dependent inflammatory response that occurs in allergic asthma, it
      could act as a potent activator of inducible nitric oxide synthase (iNOS) to
      amplify FeNO levels. OBJECTIVES: To evaluate the differences in the CD4(+) IL
      17A(+) T cell counts, serum IL-17 levels, and FeNO levels in children with mild
      intermittent to moderate to severe persistent asthma classified by using the
      Global Initiative for Asthma (GINA). METHODS: One hundred and twenty asthmatic
      children divided into the mild intermittent (n = 42), mild persistent (n = 42),
      and moderate to severe persistent (n = 36) groups, and 20 healthy controls were
      recruited for the study. Information obtained at visits included the assessment
      of asthma severity according to GINA guidelines and C-ACT, lung function
      parameters, FeNO levels, CD4(+) IL-17A(+) T cells counts from PBMCs, iNOS
      production by sputum cells and serum IL-17 levels. RESULTS: Serum IL-17 and FeNO
      levels were significantly higher in mild to severe persistent asthmatic patients
      than in intermittent asthmatics or healthy controls (P < 0.05). The percentage of
      CD4(+) IL-17A(+) T cells was higher in moderate to severe persistent asthmatics
      than in mild asthmatics (P < 0.01). Moderate to severe asthmatics (n = 5)
      exhibited greater iNOS production in sputum cells than mild cases (n = 5).
      Decreased iNOS expression in sputum cells was noted in all subjects after IL-17
      neutralizing antibody (P < 0.05). Serum IL-17 levels were positively correlated
      with FeNO (rho = 0.74; P < 0.01), negatively correlated with C-ACT (rho = -0.63;
      P < 0.01) in asthmatics. CONCLUSION AND CLINICAL RELEVANCE: CD4(+) IL-17A(+) T
      cells counts and serum IL-17 levels in conjunction with augmented FeNO levels are
      systemic markers of childhood asthma, using these markers, prediction and
      potential therapeutics for persistent asthmatics may be developed.

PMID- 23957338
TI  - In vitro drug causality assessment in Stevens-Johnson syndrome - alternatives for
      lymphocyte transformation test.
AB  - BACKGROUND: Patients with Stevens-Johnson syndrome (SJS) or toxic epidermal
      necrolysis (TEN) are often exposed simultaneously to a few potentially culprit
      drugs. However, both the standard lymphocyte transformation tests (LTT) with
      proliferation as the assay end-point as well as skin tests, if done, are often
      negative. OBJECTIVE: As provocation tests are considered too dangerous, there is
      an urgent need to identify the relevant drug in SJS/TEN and to improve
      sensitivity of tests able to identify the causative drug. METHODS: Fifteen
      patients with SJS/TEN with the ALDEN score >= 6 and 18 drug-exposed controls were
      included. Peripheral blood mononuclear cells (PBMC) were isolated and cultured
      under defined conditions with drugs. LTT was compared to the following end
      points: cytokine levels in cell culture supernatant, number of granzyme B
      secreting cells by ELISpot and intracellular staining for granulysin and IFNgamma
      in CD3(+) CD4(+), CD3(+) CD8(+) and NKp46(+) cells. To further enhance
      sensitivity, the effect of IL-7/IL-15 pre-incubation of PBMC was evaluated.
      RESULTS: Lymphocyte transformation tests was positive in only 4/15 patients
      (sensitivity 27%, CI: 8-55%). Similarly, with granzyme B-ELISpot culprit drugs
      were positive in 5/15 patients (sensitivity 33%, CI: 12-62%). The expression of
      granulysin was significantly induced in NKp46(+) and CD3(+) CD4(+) cells
      (sensitivity 40%, CI: 16-68% and 53%, CI: 27-79% respectively). Cytokine
      production could be demonstrated in 38%, CI: 14-68% and 43%, CI: 18-71% of
      patients for IL-2 and IL-5, respectively, and in 55%, CI: 23-83% for IFNgamma.
      Pre-incubation with IL-7/IL-15 enhanced drug-specific response only in a few
      patients. Specificities of tested assays were in the range of 95 (CI: 80-99%)
      100% (CI: 90-100%). CONCLUSIONS AND CLINICAL RELEVANCE: Granulysin expression in
      CD3(+) CD4(+) , Granzyme B-ELISpot and IFNgamma production considered together
      provided a sensitivity of 80% (CI: 52-96%) and specificity of 95% (80-99%). Thus,
      this study demonstrated that combining different assays may be a feasible
      approach to identify the causative drug of SJS/TEN reactions; however,
      confirmation on another group of patients is necessary.

PMID- 23957339
TI  - Activation of TLR4 induces VEGF expression via Akt pathway in nasal polyps.
AB  - BACKGROUND: Nasal polyposis is characterized by tissue remodelling and oedematous
      nasal mucosa. Vascular endothelial growth factor (VEGF) plays a significant role
      in the regulation of remodelling in nasal polyps. TLR4 activation is associated
      with VEGF expression in murine macrophages and odontoblasts. OBJECTIVE: This
      study aimed to evaluate whether lipopolysaccharide (LPS), an inducer of TLR4,
      stimulates VEGF expression and to determine the mechanism underlying VEGF
      production in nasal polyps. METHODS: Nasal polyp-derived fibroblasts (NPDFs) were
      isolated from 10 patients with nasal polyps and exposed to LPS. LPS from
      Rhodobacter sphaeroides (LRS) was used to inhibit the expression levels of TLR4,
      MyD88 and VEGF. Messenger RNA (mRNA) expression levels of TLRs, MyD88 and VEGF
      were determined by gene expression microarray and semiquantitative reverse
      transcription-PCR. Protein expression levels of TLR4 and VEGF were analysed using
      western blot, immunofluorescence staining and enzyme-linked immunosorbent assay
      (ELISA). Activation of MAPKs (ERK, p38, and JNK) and Akt was examined using
      western blot analysis. The expression level of VEGF was measured by ELISA and
      western blot analysis in ex vivo nasal polyp organ culture. RESULTS: The protein
      expression level of VEGF was increased in nasal polyp tissues compared with
      inferior turbinate tissues. LRS inhibited the mRNA and protein expression of
      TLR4, MyD88 and VEGF in LPS-stimulated NPDFs. LPS-activated MAPKs and Akt
      signals, whereas MAPK inhibitors did not inhibit VEGF expression, and only Akt
      inhibitor blocked VEGF production. LRS reduced the production of VEGF in LPS
      stimulated ex vivo organ culture. CONCLUSIONS AND CLINICAL RELEVANCE: These
      results suggest that LPS stimulates the production of VEGF through the TLR4-Akt
      signalling pathway in nasal polyps. LPS may be involved in the pathogenesis of
      nasal polyp remodelling.

PMID- 23957340
TI  - Early supplementation with Lactobacillus rhamnosus HN001 reduces eczema
      prevalence to 6 years: does it also reduce atopic sensitization?
AB  - BACKGROUND: The role of probiotics in prevention of allergic disease is still not
      clear; efficacy may depend on the timing, dose, duration, and specific probiotic
      used. Using a double-blind randomized placebo-controlled trial (Australian New
      Zealand Clinical Trials Registry: ACTRN12607000518460), we have shown that in a
      high-risk birth cohort, maternal supplementation from 35 weeks gestation until 6
      months if breastfeeding and infant supplementation from birth until 2 years with
      Lactobacillus rhamnosus HN001 (HN001) (6 * 10(9) cfu/day) halved the cumulative
      prevalence of eczema at 2 and 4 years. Bifidobacterium animalis subsp lactis
      HN019 (HN019) (9 * 10(9) cfu/day) had no significant effect. OBJECTIVE: To
      determine whether differences in effects of HN001 and HN019 on eczema persist to
      age 6 years, and to investigate effects on sensitization. METHODS: Standard
      procedures were used to assess eczema (The UK Working Party's Criteria), eczema
      severity (SCORAD), atopic sensitization [skin prick tests (SPT), total and
      specific IgE] and standard questions used for asthma, wheeze, and
      rhinoconjunctivitis. RESULTS: HN001 was associated with significantly lower
      cumulative prevalence of eczema (HR = 0.56, 95% CI 0.39-0.80), SCORAD >= 10 (HR =
      0.69, 0.49-0.98) and SPT sensitization (HR = 0.69, 95% CI 0.48-0.99). The point
      prevalence of eczema (RR = 0.66, 95% CI 0.44-1.00), SCORAD >= 10 (RR = 0.62, 95%
      CI 0.38-1.01) and SPT sensitization (RR = 0.72, 95% CI 0.53-1.00) were also
      reduced among children taking HN001. HN019 had no significant effect on any
      outcome. CONCLUSION AND CLINICAL RELEVANCE: This study provides evidence for the
      efficacy of the probiotic L. rhamnosus HN001 in preventing the development of
      eczema and possibly also atopic sensitization in high risk infants to age 6
      years. The absence of a similar effect for HN019 indicates that benefits may be
      species specific.

PMID- 23957341
TI  - Conception via in vitro fertilization and delivery by Caesarean section are
      associated with paediatric asthma incidence.
AB  - BACKGROUND: The association between perinatal factors and asthma inception is
      under rigorous investigation. Nevertheless, evidence of a correlation between
      asthma, conception via in vitro fertilization (IVF) and delivery through
      Caesarean section (C-section) is inconclusive. OBJECTIVE: We aimed to assess the
      relation of asthma incidence with IVF and C-section, after controlling for
      several potential confounding factors. METHODS: Parent-reported wheeze in the
      last 12 months (current), wheeze ever, physician-diagnosed asthma, method of
      conception, and type of delivery were recorded from questionnaires filled in by
      the parents of 2016 Greek children aged 9-13, (the Healthy Growth Study
      population). Some perinatal data were recorded from children's medical records
      and others were reported by parents; anthropometric measurements were also
      conducted in children. RESULTS: IVF was correlated with physician-diagnosed
      asthma (OR = 2.25; 95% CI = 1.11-4.56), but not with current/ever wheeze after
      adjustment for potential confounding factors. After adjustment, C-section was
      also associated with asthma (OR = 1.39; 95% CI = 1.04-1.87), but not with
      current/ever wheeze. When the association of both IVF and C-section with asthma
      was examined in the same multivariate logistic regression model, it was weakened
      to borderline significance (OR = 2.04; 95% CI = 1-4.15 and OR = 1.34; 95% CI = 1
      1.81 respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Conception via IVF and
      delivery by C-section may predispose children to future asthma development.
      Either variable could also exert a confounding effect on the link of the other to
      asthma; this may partially be accountable for inconsistencies in the findings of
      pertinent studies.

PMID- 23957342
TI  - No matrix effect in double-blind, placebo-controlled egg challenges in egg
      allergic children.
AB  - BACKGROUND: Diagnostic and accidental food allergic reactions may be modified by
      the matrix containing the allergenic food. Previous studies of double-blind,
      placebo-controlled food challenges (DBPCFCs) with peanut found an effect of the
      fat content of the challenge matrix on the severity of the challenge reactions.
      OBJECTIVE: The aim of this study was to examine whether the fat content of the
      food matrix is related to eliciting dose and reaction severity in DBPCFCs with
      heated hen's egg. METHODS: Sensitized egg allergic children (n = 59) undergoing
      DBPCFCs with egg as a routine diagnostic procedure in our tertiary care centre
      were evaluated retrospectively. Three different recipes were used for the food
      matrix: vanilla pudding, pancake and minced meat, containing 22.8%, 31.9% and
      52.7% fat (weighted average), respectively. The eliciting dose (i.e. the highest
      cumulative dose to which the child reacted) was analyzed by Kaplan-Meier log-rank
      statistic and by Cox regression. Reaction severity was quantified by using an
      index (range 1-12) and was analysed by multiple linear regression analysis.
      RESULTS: The overall influence of type of recipe on eliciting dose was not
      significant (P = 0.12). The rate of response to minced meat (with the highest fat
      content) was not significantly different from pudding [HR = 0.61 (0.26-1.45, P =
      0.26) or pancake (HR = 1.41 (0.50-3.99), P = 0.52] after adjustment for
      confounders. The type of recipe did not influence the severity of the challenge
      reaction. The severity of the challenge reaction for minced meat compared to
      pudding and pancake was 1.06 (0.52-2.16), P = 0.87 and 0.81 (0.32-2.01), P =
      0.64, respectively, after correction for confounders. CONCLUSION AND CLINICAL
      RELEVANCE: In contrast to similar research with peanut, no significant influence
      of the fat content of the matrix was found on the eliciting dose or severity of
      the reaction in 59 DBPCFCs with hen's egg. Matrix fat content differences
      comparable to those reported here may not be an important co-determinant of
      reaction severity for all allergenic foods.

PMID- 23957343
TI  - MAG-EPA resolves lung inflammation in an allergic model of asthma.
AB  - BACKGROUND: Asthma is a chronic disease characterized by airways
      hyperresponsiveness, inflammation and airways remodelling involving reversible
      bronchial obstruction. Omega-3 fatty acids and their derivatives are known to
      reduce inflammation in several tissues including lung. OBJECTIVES: The effects of
      eicosapentaenoic acid monoacylglyceride (MAG-EPA), a newly synthesized EPA
      derivative, were determined on the resolution of lung inflammation and airway
      hyperresponsiveness in an in vivo model of allergic asthma. METHODS: Ovalbumin
      (OVA)-sensitized guinea-pigs were treated or not with MAG-EPA administered per
      os. Isometric tension measurements, histological analyses, homogenate preparation
      for Western blot experiments or total RNA extraction for RT-PCR were performed to
      assess the effect of MAG-EPA treatments. RESULTS: Mechanical tension measurements
      revealed that oral MAG-EPA treatments reduced methacholine (MCh)-induced
      bronchial hyperresponsiveness in OVA-sensitized guinea-pigs. Moreover, MAG-EPA
      treatments also decreased Ca(2+) hypersensitivity of bronchial smooth muscle.
      Histological analyses and leucocyte counts in bronchoalveolar lavages revealed
      that oral MAG-EPA treatments led to less inflammatory cell recruitment in the
      lung of OVA-sensitized guinea-pigs when compared with lungs from control animals.
      Results also revealed a reduction in mucin production and MUC5AC expression level
      in OVA-sensitized animals treated with MAG-EPA. Following MAG-EPA treatments, the
      transcript levels of pro-inflammatory markers such as IL-5, eotaxin, IL-13 and IL
      4 were markedly reduced. Moreover, per os MAG-EPA administrations reduced COX2
      over-expression in OVA-sensitized animals. CONCLUSION AND CLINICAL RELEVANCE: We
      demonstrate that MAG-EPA reduces airway hyperresponsiveness and lung inflammation
      in OVA-sensitized animals, a finding consistent with a decrease in IL-4, IL-5, IL
      13, COX-2 and MUC5AC expression levels in the lung. The present data suggest that
      MAG-EPA represents a new potential therapeutic strategy for resolving
      inflammation in allergic asthma.

PMID- 23957344
TI  - Airway, apoptosis, and asthma.

PMID- 23957345
TI  - Regarding comments by Persson et al. (Airway, apoptosis, and asthma) to J. L.
      Simpson, P. G. Gibson, I. A. Yang, J. Upham, A. James, P. N. Reynolds, S. Hodge
      and AMAZES Study Research. Impaired macrophage phagocytosis in noneosinophilic
      asthma. Clin Exp Allergy 2013; 43:29-35.

PMID- 23957346
TI  - Targeting translational control as a novel way to treat inflammatory disease: the
      emerging role of microRNAs.
AB  - Chronic inflammatory diseases (e.g. asthma and chronic obstructive pulmonary
      disease)are leading causes of morbidity and mortality world-wide and effective
      treatments are limited. These disorders can often be attributed to abnormal
      immune responses to environmental stimuli and infections. Mechanisms leading to
      inflammation are complex,resulting from interactions of structural cells and
      activation of both the adaptive and innate arms of the immune system. The
      activation of structural and immune cells involves both temporary and permanent
      changes in gene expression in these cells, which underpin chronic inflammation
      and tissue dysfunction. miRNAs are small non-coding RNAs increasingly being
      recognized to play important roles in the post-transcriptional regulation of gene
      expression in mammalian cells by regulating translation. Individual miRNA scan
      exert their effects by directly inhibiting the translation or stability of
      multiple mRNAs simultaneously. Thus, the expression or blockade of function of a
      single miRNA (miR) can result in pronounced alterations in protein expression
      within a given cell. Dysregulation of miRNA expression may subsequently alter
      cellular function, and in certain situations predispose to disease. Our current
      understanding of the role of miRNA in the regulation of inflammatory disease
      (e.g. allergic diseases) remains limited. In this review, we provide an overview
      of the current understanding of miRNA biogenesis and function, the roles miRNA
      play in the regulation of immune cell function and their potential contribution
      to inflammatory diseases. We also highlight strategies to alter miRNA function
      for experimental or therapeutic gain, and discuss the potential utility and
      limitations of targeting these molecules as anti-inflammatory strategies.

PMID- 23957347
TI  - Palladium-catalyzed anti-Markovnikov hydroalkylation of homoallylic alcohols
      bearing beta-fluorines.
AB  - A palladium-catalyzed anti-Markovnikov hydroalkylation of beta,beta-difluorinated
      homoallylic alcohols with alkylzinc reagents has been developed. This method
      affords a wide range of synthetically useful gem-difluorinated compounds with
      good functional group compatibility. 

PMID- 23957348
TI  - Symmetry of support scull and vertical position stability in synchronized
      swimming.
AB  - Maintaining the body underwater in the so-called vertical position, where the
      body is inverted (head down) and balanced, is made possible by performing the
      support scull movement by the upper limbs. In synchronized swimming, the main
      criteria for judging this vertical position are maintaining body stability and
      the maximum height of the lower limbs one is able to extend out of the water.
      Therefore, it seems important to examine for any correlations between the
      symmetry of the upper limb's movement (sculling) and the ability to maintain
      balance of the body. The aim of this study was to use a dynamical asymmetry index
      (DAI) to assess the symmetry of the upper limb movements performed in
      synchronized swimming. The use of the dynamical asymmetry index is considered to
      be advantageous over the asymmetry coefficient, which is better known in
      literature on the subject and has been used by numerous authors, as it not only
      evaluates the magnitude of the asymmetry, but also indicates in which phases of
      movement asymmetry is the greatest or where it is the least significant.

PMID- 23957349
TI  - Isolation, characterization and mode of antimicrobial action against Vibrio
      cholerae of methyl gallate isolated from Acacia farnesiana.
AB  - AIMS: The antimicrobial activity of Acacia farnesiana against Vibrio cholerae has
      been demonstrated; however, no information regarding its active compound or its
      mechanism of action has been documented. METHODS AND RESULTS: The active compound
      was isolated from A. farnesiana by bioassay-guided fractionation and identified
      as methyl gallate by nuclear magnetic resonance (NMR) techniques ((1) H NMR and
      (13) C NMR). The minimum bactericidal concentration (MBC) of methyl gallate and
      its effect on membrane integrity, cytoplasmic pH, membrane potential, ATP
      synthesis and gene expression of cholera toxin (ctx) from V. cholerae were
      determined. The MBC of methyl gallate ranged from 30 +/- 1 to 50 +/- 1 MUg ml(-1)
      . Methyl gallate affected cell membrane integrity, causing a decrease in
      cytoplasmic pH (pHin , from 7.3 to <3.0), and membrane hyperpolarization, and ATP
      was no longer produced by the treated cells. However, methyl gallate did not
      affect ctx gene expression. CONCLUSIONS: Methyl gallate is a major antimicrobial
      compound from A. farnesiana that disturbs the membrane activity of V. cholerae.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The effects of methyl gallate validate
      several traditional antimicrobial uses of A. farnesiana, and it is an attractive
      alternative to control V. cholerae.

PMID- 23957351
TI  - On the photoionization spectrum of propyne: a fully ab initio simulation of the
      low-energy spectrum including the Jahn-Teller effect and the spin-orbit
      interaction.
AB  - The low energy photoionization spectrum of propyne (CH3-CCH), which reveals the
      vibronic structure of the propyne cation, is simulated using vibronic coupling
      theory. The spin-orbit interaction is included using an intensity borrowing
      approach, enabling determination of the (X(2)E1/2,3/2, v = 0) splitting and the
      relative photoionization intensity of these closely spaced levels. The results
      are compared with recent experimental studies and misstatements are corrected. 

PMID- 23957350
TI  - The conserved Mediator subunit MDT-15 is required for oxidative stress responses
      in Caenorhabditis elegans.
AB  - Reactive oxygen species (ROS) play important signaling roles in metazoans, but
      also cause significant molecular damage. Animals tightly control ROS levels using
      sophisticated defense mechanisms, yet the transcriptional pathways that induce
      ROS defense remain incompletely understood. In the nematode Caenorhabditis
      elegans, the transcription factor SKN-1 is considered a master regulator for
      detoxification and oxidative stress responses. Here, we show that MDT-15, a
      subunit of the conserved Mediator complex, is also required for oxidative stress
      responses in nematodes. Specifically, mdt-15 is required to express SKN-1 targets
      upon chemical and genetic increase in SKN-1 activity. mdt-15 is also required to
      express genes in SKN-1-dependent and SKN-1-independent fashions downstream of
      insulin/IGF-1 signaling and for the longevity of daf-2/insulin receptor mutants.
      At the molecular level, MDT-15 binds SKN-1 through a region distinct from the
      classical transcription-factor-binding KIX-domain. Moreover, mdt-15 is essential
      for the transcriptional response to and survival on the organic peroxide tert
      butyl-hydroperoxide (tBOOH), a largely SKN-1-independent response. The MDT-15
      interacting nuclear hormone receptor, NHR-64, is specifically required for tBOOH
      but not arsenite resistance, but NHR-64 is dispensable for the transcriptional
      response to tBOOH. Hence, NHR-64 and MDT-15's mode of action remain elusive.
      Lastly, the role of MDT-15 in oxidative stress defense is functionally separable
      from its function in fatty acid metabolism, as exogenous polyunsaturated fatty
      acid complementation rescues developmental, but not stress sensitivity phenotypes
      of mdt-15 worms. Our findings reveal novel conserved players in the oxidative
      stress response and suggest a broad cytoprotective role for MDT-15. 

PMID- 23957352
TI  - Combined treatment of mulberry leaf and fruit extract ameliorates obesity-related
      inflammation and oxidative stress in high fat diet-induced obese mice.
AB  - The aim of this study was to investigate whether a combined treatment of mulberry
      leaf extract (MLE) and mulberry fruit extract (MFE) was effective for improving
      obesity and obesity-related inflammation and oxidative stress in high fat (HF)
      diet-induced obese mice. After obesity was induced by HF diet for 9 weeks, the
      mice were divided into eight groups: (1) lean control, (2) HF diet-induced obese
      control, (3) 1:1 ratio of MLE and MFE at doses of 200 (L1:1), (4) 500 (M1:1), and
      (5) 1000 (H1:1) mg/kg per day, and (6) 2:1 ratio of MLE and MFE at doses of 200
      (L2:1), (7) 500 (M2:1), and (8) 1000 (H2:1) mg/kg per day. All six combined
      treatments significantly lowered body weight gain, plasma triglycerides, and
      lipid peroxidation levels after the 12-week treatment period. Additionally, all
      combined treatments suppressed hepatic fat accumulation and reduced epididymal
      adipocyte size. These improvements were accompanied by decreases in protein
      levels of proinflammatory markers (tumor necrosis factor-alpha, C-reactive
      protein, interleukin-1, inducible nitric oxide synthase, and phospho-nuclear
      factor-kappa B inhibitor alpha) and oxidative stress markers (heme oxygenase-1
      and manganese superoxide dismutase). M2:1 was the most effective ratio and dose
      for the improvements in obesity, inflammation, and oxidative stress. These
      results demonstrate that a combined MLE and MFE treatment ameliorated obesity and
      obesity-related metabolic stressors and suggest that it can be used as a means to
      prevent and/or treat obesity.

PMID- 23957353
TI  - Antrodia camphorata grown on germinated brown rice inhibits HT-29 human colon
      carcinoma proliferation through inducing G0/G1 phase arrest and apoptosis by
      targeting the beta-catenin signaling.
AB  - Antrodia camphorata (AC) has been used as a traditional medicine to treat food
      and drug intoxication, diarrhea, abdominal pain, hypertension, pruritis (skin
      itch), and liver cancer in East Asia. In this study, we investigated anticancer
      activities of AC grown on germinated brown rice (CBR) in HT-29 human colon cancer
      cells. We found that the inhibitory efficacy of CBR 80% ethanol (EtOH) extract on
      HT-29 and CT-26 cell proliferation was more effective than ordinary AC EtOH 80%
      extract. Next, 80% EtOH extract of CBR was further separated into four fractions;
      hexane, ethyl acetate (EtOAc), butanol (BuOH), and water. Among them, CBR EtOAc
      fraction showed the strongest inhibitory activity against HT-29 cell
      proliferation. Therefore, CBR EtOAc fraction was chosen for further studies.
      Annexin V-fluorescein isothiocyanate staining data indicated that CBR EtOAc
      fraction induced apoptosis. Induction of G0/G1 cell cycle arrest on human colon
      carcinoma cell was observed in CBR EtOAc fraction-treated cells. We found that
      CBR decreased the level of proteins involved in G0/G1 cell cycle arrest and
      apoptosis. CBR EtOAc fraction inhibited the beta-catenin signaling pathway,
      supporting its suppressive activity on the level of cyclin D1. High performance
      liquid chromatography analysis data indicated that CBR EtOAc fraction contained
      adenosine. This is the first investigation that CBR has a greater potential as a
      novel chemopreventive agent than AC against colon cancer. These data suggest that
      CBR might be useful as a chemopreventive agent against colorectal cancer.

PMID- 23957354
TI  - Bifunctional chemopreventive effects of Adenocaulon himalaicum through induction
      of detoxification enzymes and apoptosis.
AB  - Phase II detoxification enzymes are known to play essential roles in the
      detoxification and elimination of activated carcinogens during tumor initiation,
      while apoptosis is one of the most important chemopreventive targets for
      inhibiting tumor promotion in cancer. In this study, we investigated the cancer
      chemopreventive activity of two plant extracts, the ethanolic extract of
      Adenocaulon himalaicum (AHE) and the butanolic fraction of AHE (AHB). Both, the
      AHE and AHB induced NQO1 activity and had relatively high chemoprevention indices
      (CI=12.4). The AHE and AHB were associated with increased NQO1 and HO-1 mRNA
      levels via Nrf2-ARE pathway activation. In addition, the AHB increased CYP1A1
      activity through AhR-XRE pathway activation. We also found that the AHE and AHB
      induced apoptosis, as evidenced by phosphatidylserine externalization, an
      increase in the sub-G0/G1 content, chromatin condensation, poly(ADP-ribose)
      polymerase cleavage, and p53 induction. These data suggest that AHE and AHB act
      as bifunctional inducers and that their chemopreventive effects result from the
      biphasic induction of phase II detoxification enzymes and apoptosis. Therefore,
      these results suggest that A. himalaicum plant extracts have potential for use as
      chemopreventive agents for the prevention and/or treatment of human cancers.

PMID- 23957355
TI  - Mangiferin from Salacia chinensis prevents oxidative stress and protects
      pancreatic beta-cells in streptozotocin-induced diabetic rats.
AB  - Oxidative stress in diabetic tissues is a consequence of free radical
      accumulation with concurrently impaired natural antioxidants status and results
      in oxidative tissue damage. The present study investigated the protective effects
      of mangiferin against pancreatic beta-cell damage and on the antioxidant defense
      systems in streptozotocin (STZ)-induced diabetic rats. Diabetes was
      experimentally induced by a single intraperitoneal injection of STZ. Oxidative
      stress biomarkers such as tissue malondialdehyde, hydroperoxides, reduced
      glutathione (GSH) content, and nonenzymatic antioxidants were measured.
      Biochemical observations were further substantiated with histological examination
      and ultrastructural studies in the pancreas of diabetic, glibenclamide and
      mangiferin-treated diabetic rats (dosage of 40 mg/kg body weight daily for 30
      days). Oral administration of mangiferin and glibenclamide to diabetic rats
      significantly decreased the level of blood glucose and increased levels of
      insulin. Additionally, mangiferin treatment significantly modulated the
      pancreatic nonenzymatic antioxidants status (vitamin C, vitamin E, ceruloplasmin,
      and reduced GSH content) and other oxidative stress biomarkers. The
      histoarchitecture of diabetic rats showed degenerated pancreas with lower beta
      cell counts, but mangiferin treatment effectively regenerated insulin secreting
      islet cells. The electron microscopic study revealed damaged nuclear envelope and
      mitochondria and fewer secretory granules in pancreas of diabetic rats; however,
      mangiferin treatment nearly normalized pancreatic architecture. The present
      findings suggest that mangiferin treatment exerts a therapeutic protective nature
      in diabetes by decreasing oxidative stress and protecting against pancreatic beta
      cell damage, which may be attributable to its antioxidative properties.

PMID- 23957356
TI  - Lentinula edodes (shiitake) modulates chemically induced mutagenesis by enhancing
      pitting.
AB  - This study was undertaken to understand how Lentinula edodes modulates in vivo
      mutagenesis induced by alkylating agents in bone marrow and peripheral blood as
      described in our previous article. Male Swiss mice were pretreated for 15
      consecutive days with aqueous extracts prepared from L. edodes, after which, the
      number of circulating blood cells, normal erythroid bone marrow cell cycling, and
      phagocytosis of micronucleated reticulocyte (MNRET) and activation of spleen
      macrophages were assessed. The results indicate that the antimutagenicity seen in
      bone marrow and peripheral blood is exerted by distinct compounds with different
      actions. The antimutagenic effect in bone marrow is exerted by compounds subject
      to degradation at deep-freeze storage temperature of -20 degrees C. On the other
      hand, compounds responsible for antimutagenicity in peripheral blood are not
      subject to degradation at -20 degrees C. The results also indicate that the
      antimutagenic action in peripheral blood leading to the reduction of circulating
      MNRET occurs in the spleen primarily through a phagocytic activity due to higher
      macrophage numbers and probably not due to the enhanced activation state of
      individual cells.

PMID- 23957357
TI  - Antinociceptive and anti-inflammatory activities of Sargassum wightii and
      Halophila ovalis sulfated polysaccharides in experimental animal models.
AB  - The present study investigated the effects of sulfated polysaccharides from brown
      seaweed Sargassum wightii (Sw-SP) and seagrass Halophila ovalis (Ho-SP) in
      nociceptive and inflammatory models. In the formalin test, Sw-SP and Ho-SP
      significantly reduced licking time in both phases of the test at a dose of 10
      mg/kg. In the hot plate test, the antinociceptive effect was observed only in
      animals treated with 10 mg/kg of Sw-SP and 5, 10 mg/kg of Ho-SP, suggesting that
      the analgesic effect occurs through a central action mechanism at the higher
      dose. Sw-SP and Ho-SP (10 mg/kg) significantly inhibited paw edema induced by
      carrageenan, especially at 3 h after treatment and potentially decreased
      neutrophil migration by 53% and 52%, respectively. In Freund's adjuvant-induced
      arthritic rats, there was a significant increase in the rat paw volume and
      decrease in body weight, but in Sw-SP- and Ho-SP-treated groups (10 mg/kg), a
      significant reduction in paw volume and a normal gain in body weight were
      observed. The present results indicate that Sw-SP and Ho-SP possess
      antinociceptive and anti-inflammatory effects and have potential usefulness for
      development as therapeutic agents.

PMID- 23957358
TI  - Rutabaga (Brassica napus L. var. napobrassica) seeds, roots, and sprouts: a novel
      kind of food with antioxidant properties and proapoptotic potential in Hep G2
      hepatoma cell line.
AB  - Although rutabaga (Brassica napus L. var. napobrassica) is a popular crop,
      especially in North Europe and North America, its sprouts are a new kind of
      vegetable. Rutabaga roots, and particularly sprouts, have not been investigated
      so far for antioxidant and anticancer effect on human tumor cells (Hep G2).
      Therefore, in vitro tests were conducted to find out whether rutabaga seeds,
      roots, and sprouts exert a cytotoxic effect on mammalian cells and combine them
      with other biological properties of particular parts of the plant. Rutabaga
      methanol extracts were measured for total phenolic, total flavonoid
      concentrations, and total antioxidant activity. Cytotoxicity of the investigated
      extracts was measured using 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium
      bromide assay in Chinese hamster ovary cells (CHO-K1) and Hep G2 cells culture.
      Cell membrane integrity was assessed in CHO-K1 and Hep G2 cells by luminescence
      ToxiLight BioAssay. The results of the investigation have shown that sprouts have
      significantly higher antioxidant activity than seeds and roots, which may result
      from different contents of polyphenols. Rutabaga extracts (especially 8 day
      sprouts) inhibited the tumor cell line Hep G2 proliferation and had a slight
      effect on the normal mammalian CHO-K1 culture. An advanced analysis of previously
      observed morphological changes and cytotoxic properties demonstrated that the
      evaluated extracts exerted cell death via apoptosis. These findings strongly
      suggest that one of the biological activities of rutabaga is antiproliferative
      and proapoptotic potential specific to tumor cells. The obtained results
      demonstrate the antioxidant property of rutabaga and its potential as a
      nutritional supplement in cancer prevention. These findings also strongly
      advocate the application of rutabaga sprouts (especially harvested in conditions
      presented in this article) in functional food.

PMID- 23957359
TI  - Antioxidant properties of the wild edible mushroom Lactarius salmonicolor.
AB  - The fruiting bodies of the edible mushroom Lactarius salmonicolor (Russulaceae)
      collected from the wild were extracted with solvents of increasing polarity and
      evaluated for their antioxidant capacity by 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      radical scavenging method. Additionally, their total phenolic content was
      evaluated by a modification of the Folin-Ciocalteu method. The methanol extract
      showed the most potent radical scavenging activity (inhibition of 36.7% of DPPH
      at 3 mg/mL and 6.8 mg gallic acid equivalents/g of dry extract), and was further
      fractionated. Total phenolics and antioxidant activity found to be significant
      higher in the fractions of increased polarity. The phytochemical investigation
      which was performed by chromatographic and spectrometric techniques led to the
      isolation of nine compounds from the methanol extract and the identification of
      10 fatty acids and fatty acids esters from the dichloromethane extract.
      Evaluation of the antioxidant activity of isolated compounds showed p
      hydroxybenzoic acid (4) to be the most active. Among the various compounds found,
      the rare azulene type 7-acetyl-4-methylazulene-1-carboxylic acid (1) has been
      identified, which had been isolated only once before from L. deliciosus.
      Therefore, this compound seems to have some chemotaxonomic value for Lactrarius
      species exuding orange to red milk.

PMID- 23957360
TI  - Ginsenoside Rh2 improves learning and memory in mice.
AB  - A wide range of plant foods and dietary supplements are able to modify the
      functioning of the central nervous system. In the present study, we observed that
      oral administration of ginsenoside Rh2 (10 mg/mL) for 3 weeks significantly
      improved spatial learning and memory. Spatial memory and learning was evaluated
      in mice by hippocampus-dependent tasks (Morris water maze test) and
      immunohistochemical marker of cell genesis bromodeoxyuridine. Ginsenoside Rh2
      treatment (30 days) promoted cell survival and genesis. Further, ginsenoside Rh2
      treatment in enriched condition had no significant effects on cell survival
      compared with standard condition exposure. These results revealed that
      ginsenoside Rh2-mediated spatial learning and memory improvement was associated
      with cell genesis and survival and may be parallel to the mechanism of
      environmental enrichment. Therefore, ginsenoside Rh2 may have efficacy as a
      dietary supplement for spatial learning and memory improvement.

PMID- 23957361
TI  - Highly anisotropic rhenium(IV) complexes: new examples of mononuclear single
      molecule magnets.
AB  - The rhenium(IV) complex (NBu4)2[ReBr4(ox)] (1) (ox = oxalate and NBu4(+) = tetra
      n-butylammonium cation) has been prepared and its crystal structure determined by
      X-ray diffraction. The structure is made up of discrete [ReBr4(ox)](2-) anions
      and bulky NBu4(+) cations. Each [ReBr4(ox)](2-) anion is surrounded by six
      NBu4(+) cations, which preclude any significant intermolecular contact between
      the anionic entities, the shortest rhenium...rhenium distance being 9.373(1) A.
      Variable temperature dc and ac magnetic susceptibility measurements and field
      dependent magnetization experiments on polycrystalline samples of 1 reveal the
      occurrence of highly anisotropic magnetically isolated Re(IV) centers (S(Re) =
      3/2), which exhibit slow relaxation of the magnetization at very low temperatures
      in a dc field. Ac measurements conducted on a polycrystalline sample of the
      complex (NBu4)2[ReCl4(ox)] (2) [compound isostructural to 1 whose structure and
      dc magnetic susceptibility study were previously reported in Tomkiewicz, A.;
      Bartczak, T. J.; Kruszynski, R.; Mrozinski, J. J. Mol. Struct. 2001, 595, 225]
      show a similar behavior, both complexes thus constituting new examples of
      mononuclear single-molecule magnets. High-frequency and -field electron
      paramagnetic resonance on polycrystalline samples of 1 and 2 and on single
      crystals of 2 allowed for the determination for the first time of the negative
      sign and confirmed a significant magnitude and rhombicity (E/D) of the zero-field
      splitting tensor of the [ReCl4(ox)](2-) and [ReBr4(ox)](2-) centers, originating
      from a combination of spin-orbit coupling and low molecular symmetry. D and E
      values of 1 and 2 were estimated through magnetization measurements and
      theoretically calculated through complete active space and density functional
      theory methodologies.

PMID- 23957362
TI  - GRank: a middleware search engine for ranking genes by relevance to given genes.
AB  - BACKGROUND: Biologists may need to know the set of genes that are semantically
      related to a given set of genes. For instance, a biologist may need to know the
      set of genes related to another set of genes known to be involved in a specific
      disease. Some works use the concept of gene clustering in order to identify
      semantically related genes. Others propose tools that return the set of genes
      that are semantically related to a given set of genes. Most of these gene
      similarity measures determine the semantic similarities among the genes based
      solely on the proximity to each other of the GO terms annotating the genes, while
      overlook the structural dependencies among these GO terms, which may lead to low
      recall and precision of results. RESULTS: We propose in this paper a search
      engine called GRank, which overcomes the limitations of the current gene
      similarity measures outlined above as follows. It employs the concept of
      existence dependency to determine the structural dependencies among the GO terms
      annotating a given set of gene. After determining the set of genes that are
      semantically related to input genes, GRank would use microarray experiment to
      rank these genes based on their degree of relativity to the input genes. We
      evaluated GRank experimentally and compared it with a comparable gene prediction
      tool called DynGO, which retrieves the genes and gene products that are relatives
      of input genes. Results showed marked improvement. CONCLUSIONS: The experimental
      results demonstrated that GRank overcomes the limitations of current gene
      similarity measures. We attribute this performance to GRank's use of existence
      dependency concept for determining the semantic relationships among gene
      annotations. The recall and precision values for two benchmarking datasets showed
      that GRank outperforms DynGO tool, which does not employ the concept of existence
      dependency. The demo of GRank using 11000 KEGG yeast genes and a Gene Expression
      Omnibus (GEO) microarray file named "GSM34635.pad" is available at:
      http://ecesrvr.kustar.ac.ae:8080/ (click on the link labelled Gene Ontology 2).

PMID- 23957363
TI  - Asymmetrical switch costs in bilingual language production induced by reading
      words.
AB  - We examined language-switching effects in French-English bilinguals using a
      paradigm where pictures are always named in the same language (either French or
      English) within a block of trials, and on each trial, the picture is preceded by
      a printed word from the same language or from the other language. Participants
      had to either make a language decision on the word or categorize it as an animal
      name or not. Picture-naming latencies in French (Language 1 [L1]) were slower
      when pictures were preceded by an English word than by a French word,
      independently of the task performed on the word. There were no language-switching
      effects when pictures were named in English (L2). This pattern replicates
      asymmetrical switch costs found with the cued picture-naming paradigm and shows
      that the asymmetrical pattern can be obtained (a) in the absence of artificial
      (nonlinguistic) language cues, (b) when the switch involves a shift from
      comprehension in 1 language to production in another, and (c) when the naming
      language is blocked (univalent response). We concluded that language switch costs
      in bilinguals cannot be reduced to effects driven by task control or response
      selection mechanisms.

PMID- 23957364
TI  - Compound cuing in free recall.
AB  - According to the retrieved context theory of episodic memory, the cue for recall
      of an item is a weighted sum of recently activated cognitive states, including
      previously recalled and studied items as well as their associations. We show that
      this theory predicts there should be compound cuing in free recall. Specifically,
      the temporal contiguity effect should be greater when the 2 most recently
      recalled items were studied in contiguous list positions. A meta-analysis of
      published free recall experiments demonstrates evidence for compound cuing in
      both conditional response probabilities and interresponse times. To help rule out
      a rehearsal-based account of these compound cuing effects, we conducted an
      experiment with immediate, delayed, and continual-distractor free recall
      conditions. Consistent with retrieved context theory but not with a rehearsal
      based account, compound cuing was present in all conditions, and was not
      significantly influenced by the presence of interitem distractors.

PMID- 23957365
TI  - Distracted by your mind? Individual differences in distractibility predict mind
      wandering.
AB  - Attention may be distracted from its intended focus both by stimuli in the
      external environment and by internally generated task-unrelated thoughts during
      mind wandering. However, previous attention research has focused almost
      exclusively on distraction by external stimuli, and the extent to which mind
      wandering relates to external distraction is as yet unclear. In the present
      study, the authors examined the relationship between individual differences in
      mind wandering and in the magnitude of distraction by either response-competing
      distractors or salient response-unrelated and task-irrelevant distractors. Self
      reported susceptibility to mind wandering was found to positively correlate with
      task-irrelevant distraction but not with response-competition interference. These
      results reveal mind wandering as a manifestation of susceptibility to task
      irrelevant distraction and establish a laboratory measure of general
      susceptibility to irrelevant distraction, including both internal and external
      sources.

PMID- 23957366
TI  - Relating the content and confidence of recognition judgments.
AB  - The Remember/Know procedure, developed by Tulving (1985) to capture the
      distinction between the conscious correlates of episodic and semantic retrieval,
      has spawned considerable research and debate. However, only a handful of reports
      have examined the recognition content beyond this dichotomous simplification. To
      address this, we collected participants' written justifications in support of
      ordinary old/new recognition decisions accompanied by confidence ratings using a
      3-point scale (high/medium/low). Unlike prior research, we did not provide the
      participants with any descriptions of Remembering or Knowing and thus, if the
      justifications mapped well onto theory, they would do so spontaneously. Word
      frequency analysis (unigrams, bigrams, and trigrams), independent ratings, and
      machine learning techniques (Support Vector Machine [SVM]) converged in
      demonstrating that the linguistic content of high and medium confidence
      recognition differs in a manner consistent with dual process theories of
      recognition. For example, the use of "I remember," particularly when combined
      with temporal or perceptual information (e.g., "when," "saw," "distinctly"), was
      heavily associated with high confidence recognition. Conversely, participants
      also used the absence of remembering for personally distinctive materials as
      support for high confidence new reports ("would have remembered"). Thus,
      participants afford a special status to the presence or absence of remembering
      and use this actively as a basis for high confidence during recognition
      judgments. Additionally, the pattern of classification successes and failures of
      a SVM was well anticipated by the dual process signal detection model of
      recognition and inconsistent with a single process, strictly unidimensional
      approach.

PMID- 23957367
TI  - "A long time ago, in a context far, far away": retrospective time estimates and
      internal context change.
AB  - This investigation aimed to establish retrospective time judgments as markers of
      internal context change across 2 memory paradigms, the effects of which have been
      attributed to internal context change by some researchers. Experiment 1 involved
      the list-method directed forgetting paradigm and established that the forget
      group significantly overestimated the duration of the experiment compared with
      the remember group. Experiment 2 involved the list-before-last paradigm, whereby
      participants studied 3 lists, and in between encoding of List 2 and List 3, some
      participants retrieved List 1, whereas the control participants restudied List 1.
      The results showed that the retrieval group significantly overestimated the
      duration of the experiment compared with the restudy group. Overall, these
      results support the context-change interpretation of these paradigms, and they
      also support the contextual-change hypothesis of retrospective timing (Block &
      Reed, 1978).

PMID- 23957368
TI  - Delicate refinement of surface nanotopography by adjusting TiO2 coating chemical
      composition for enhanced interfacial biocompatibility.
AB  - Surface topography and chemistry have significant influences on the biological
      performance of biomedical implants. Our aim is to produce an implant surface with
      favorable biological properties by dual modification of surface chemistry and
      topography in one single simple process. In this study, because of its chemical
      stability, excellent corrosion resistance, and biocompatibility, titanium oxide
      (TiO2) was chosen to coat the biomedical Ti alloy implants. Biocompatible
      elements (niobium (Nb) and silicon (Si)) were introduced into TiO2 matrix to
      change the surface chemical composition and tailor the thermophysical properties,
      which in turn leads to the generation of topographical features under specific
      thermal history of plasma spraying. Results demonstrated that introduction of
      Nb2O5 resulted in the formation of Ti0.95Nb0.95O4 solid solution and led to the
      generation of nanoplate network structures on the composite coating surface. By
      contrast, the addition of SiO2 resulted in a hairy nanostructure and coexistence
      of rutile and quartz phases in the coating. Additionally, the introduction of
      Nb2O5 enhanced the corrosion resistance of TiO2 coating, whereas SiO2 did not
      exert much effect on the corrosion behaviors. Compared to the TiO2 coating, TiO2
      coating doped with Nb2O5 enhanced primary human osteoblast adhesion and promoted
      cell proliferation, whereas TiO2 coatings with SiO2 were inferior in their
      bioactivity, compared to TiO2 coatings. Our results suggest that the
      incorporation of Nb2O5 can enhance the biological performance of TiO2 coatings by
      changing the surface chemical composition and nanotopgraphy, suggesting its
      potential use in modification of biomedical TiO2 coatings in orthopedic
      applications. 

PMID- 23957369
TI  - The comparative reproductive biology of a tetraploid species, Hedychium villosum,
      and its diploid progenitor H. tenuiflorum (Zingiberaceae).
AB  - The evolutionary advantages of polyploidy may result from a number of changes in
      floral traits and breeding system, which may enable polyploids to exploit new
      habitats and become widespread. In this study, we comparatively investigated the
      floral biology of the tetraploid species Hedychium villosum and its diploid
      progenitor H. tenuiflorum, to assess reproductive divergence between the two
      species. The results showed that flowers of the tetraploid species last longer
      and produce more nectar than did diploid species. The flowering times of the two
      species did not overlap at all. Observations of floral visitors in natural
      populations demonstrated that butterflies and hawkmoths were effective
      pollinators of both species, but there was a significant difference in butterfly
      and hawkmoth assemblages between the two species. The hand-pollination
      experiments and pollen tube growth experiments suggested that diploid H.
      tenuiflorum was self-incompatible, while tetraploid H. villosum was completely
      self-compatible. H. villosum has a much wider distribution range and occupies
      more diverse habitats than H. tenuiflorum. Polyploidisation may enable tetraploid
      H. villosum to exploit new habitats previously unavailable to diploid H.
      tenuiflorum.

PMID- 23957370
TI  - Morphologic characteristics of blastic plasmacytoid dendritic cell neoplasm: a
      case report.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive
      lymphoma derived from plasmacytoid dendritic cells or precursor dendritic cells.
      Despite some 240 reported cases, its morphology and especially ultrastructure has
      not been satisfactorily studied. A case is reported of a 13 year old boy, who,
      despite chemotherapy, died within a 12-month period. The electron microscopy
      findings - microvillous processes, nuclei with slight irregularities, a moderate
      amount of heterochromatin, and rough endoplasmic reticulum in the form of long,
      narrow profiles, often in parallel arrangements - taken together, serve to
      distinguish BPDCN from other neoplastic cells, such as monocytes, plasma cells
      and the cells of chronic lymphocyte leukemia.

PMID- 23957371
TI  - Lung disease, T-cells and inflammation in common variable immunodeficiency
      disorders.
AB  - INTRODUCTION: Besides hypogammaglobulinemia and recurrent infections,
      abnormalities of T-cells might contribute to lung damage in common variable
      immunodeficiency disorders (CVID). MATERIALS AND METHODS: In 16 adult patients,
      the majority of whom had pulmonary abnormalities, we studied T-cell subsets and
      markers of inflammation in bronchoalveolar lavage fluid (BALF) and blood and
      their relations with pulmonary function and high resolution computed tomography
      (HRCT). RESULTS: We demonstrated that some of the lymphocyte abnormalities
      previously demonstrated in peripheral blood from CVID patients, such as low
      CD4/CD8 T-cell ratio, were also present in BALF. Moreover, low BALF CD4/CD8 ratio
      (<= 1), found in seven patients, was significantly associated with higher blood
      CD8+ cell count and to lower values of the lung function variables; forced
      expiratory volume (FVC), total lung capacity (TLC), vital capacity (VC) and
      residual volume (RV) in % of predicted. The expression of the inflammatory
      markers HLA-DR and CCR5 on T-cells was significantly higher, and the expression
      of CCR7 significantly lower, in BALF compared to blood, possibly reflecting an
      inflammatory/cytotoxic T-cell phenotype within pulmonary tissue in CVID.
      Furthermore, patients with bronchiectasis had higher concentrations of the pro
      inflammatory cytokine TNFalpha in plasma, compared to those without. CONCLUSION:
      Our findings suggest that inflammation and T-cell activation may be involved in
      the immunopathogenesis of pulmonary complications in CVID.

PMID- 23957372
TI  - Arterial stiffness, body fat compartments, central hemodynamics, renal function
      and left atrial size.
AB  - BACKGROUND: Left atrial (LA) size is an important predictor of stroke, death, and
      atrial fibrillation. It was demonstrated recently that body fat, arterial
      stiffness and renal functions are associated with LA diameter. However, data are
      lacking for comprehensive assessments of all these risk factors in a single
      population. Therefore, the aim of the present study was to investigate the
      association between LA size and different fat descriptors, central hemodynamics,
      arterial stiffness, and renal function in healthy subjects. METHODS: To this end,
      body fat percentage, abdominal, subcutaneous fat, and general descriptors of body
      fat were estimated in 162 healthy subjects (mean age 51 years). Echocardiography
      was performed to assess LA diameter. Arterial stiffness and peripheral and
      central hemodynamics were estimated by digital volume pulse analysis and pulse
      wave analysis. Glomerular filtration rate was estimated by MDRD formula. RESULTS:
      There were significant (p < 0.05) bivariate correlations between LA diameter and
      all descriptors of body fat (except subcutaneous fat). Arterial stiffness and
      estimated glomerular filtration rate (eGFR) were also significantly correlated
      with LA size. Multiple regression analysis including all significant confounders,
      such as sex, mean arterial pressure, arterial stiffness, eGFR and body fat
      descriptors, explained 35% of variance in LA diameter. CONCLUSIONS: In
      conclusion, the present study reveals significant, independent relationships
      between body fat, arterial stiffness, and LA size.

PMID- 23957373
TI  - Editorial: do clinical services need to take conduct disorder more seriously?
AB  - Oppositional defiant disorder (ODD) and conduct disorder are common disorders and
      frequent reasons for referral to child and adolescent mental health services
      (CAMHS). Figures from epidemiological studies in the US suggest that around 10%
      of children suffer from ODD and similar numbers from CD. Data from the UK
      estimates that around 6% of children and young people aged 5 to 16 years have a
      clinically diagnosed conduct disorder in England, with much higher rates in males
      than females. 

PMID- 23957374
TI  - Targeting the 'Janus face' of the B2-bradykinin receptor.
AB  - INTRODUCTION: Kinins are main active mediators of the kallikrein-kinin system
      (KKS) via bradykinin type 1 inducible (B1R) and type 2 constitutive (B2R)
      receptors. B2R mediates most physiological bradykinin (BK) responses, including
      vasodilation, natriuresis, NO, prostaglandins release. AREAS COVERED: The article
      summarizes knowledge on kinins, B2R signaling and biological functions;
      highlights crosstalks between B2R and renin-angiotensin system (RAS). The double
      role (Janus face) in physiopathology, namely the beneficial protection of the
      endothelium, which forms the basis for the therapeutical utilization of B2
      receptor agonists, on the one side, and the involvement of B2R in inflammation or
      infection diseases and in pain mechanisms, which justifies the use of B2R
      antagonists, on the other side, is extensively analyzed. EXPERT OPINION: For
      decades, the B2R has been unconsciously activated during angiotensin-converting
      enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) treatments. Whether
      direct B2R targeting with stable agonists could bring additional therapeutic
      benefit to RAS inhibition should be investigated. Efficacy, established in
      experimental models, should be confirmed by translational studies in
      cardiovascular pathologies, glaucoma, Duchenne cardiopathy and during brain
      cancer therapy. The other face of B2R is targeted by antagonists already approved
      to treat hereditary angioedema. The use of antagonists could be extended to other
      angioedema and efficacy tested against acute pain and inflammatory diseases.

PMID- 23957375
TI  - Reliability of three Benton Judgment of Line Orientation short forms in
      idiopathic Parkinson's disease.
AB  - Individuals with Parkinson's disease (PD) often exhibit deficits in visuospatial
      functioning throughout the course of their disease. These deficits should be
      carefully assessed as they may have implications for patient safety and disease
      severity. One of the most commonly administered tests of visuospatial ability,
      the Benton Judgment of Line Orientation (JLO), consists of 30 pairs of lines
      requiring the patient to match the orientation of two lines to an array of 11
      lines on a separate page. Reliable short forms have been constructed out of the
      full JLO form, but the reliability of these forms in PD has yet to be examined.
      Recent functional MRI studies examining the JLO demonstrate right parietal and
      occipital activation, as well as bilateral frontal activation and PD is known to
      adversely affect these pathways. We compared the reliability of the original full
      form to three unique short forms in a sample of 141 non-demented, idiopathic PD
      patients and 56 age- and education-matched controls. Results indicated that a two
      thirds length short form can be used with high reliability and classification
      accuracy in patients with idiopathic PD. The other short forms performed in a
      similar, though slightly less reliable manner. 

PMID- 23957376
TI  - Trough colistin plasma level is an independent risk factor for nephrotoxicity: a
      prospective observational cohort study.
AB  - BACKGROUND: Data regarding the most efficacious and least toxic schedules for the
      use of colistin are scarce. The aim of this study was to determine the incidence
      and the potential risk factors of colistin-associated nephrotoxicity including
      colistin plasma levels. METHODS: A prospective observational cohort study was
      conducted for over one year in patients receiving intravenous colistin
      methanesulfonate sodium (CMS). Blood samples for colistin plasma levels were
      collected immediately before (Cmin) and 30 minutes after CMS infusion (Cmax).
      Renal function was assessed at baseline, on day 7 and at the end of treatment
      (EOT). Severity of acute kidney injury (AKI) was defined by the RIFLE (risk,
      injury, failure, loss, and end-stage kidney disease) criteria. RESULTS: One
      hundred and two patients met the inclusion criteria. AKI related to CMS treatment
      on day 7 and at the end of treatment (EOT) was observed in 26 (25.5%) and 50
      (49.0%) patients, respectively. At day 7, Cmin (OR, 4.63 [2.33-9.20]; P < 0.001)
      was the only independent predictor of AKI. At EOT, the Charlson score (OR 1.26
      [1.01-1.57]; P = 0.036), Cmin (OR 2.14 [1.33-3.42]; P = 0.002), and concomitant
      treatment with >= 2 nephrotoxic drugs (OR 2.61 [1.0-6.8]; P = 0.049) were
      independent risk factors for AKI. When Cmin was evaluated as a categorical
      variable, the breakpoints that better predicted AKI were 3.33 mg/L (P < 0.001) on
      day 7 and 2.42 mg/L (P < 0.001) at EOT. CONCLUSIONS: When using the RIFLE
      criteria, colistin-related nephrotoxicity is observed in a high percentage of
      patients. Cmin levels are predictive of AKI. Patients who receive intravenous
      colistin should be closely monitored and Cmin might be a new useful tool to
      predict AKI.

PMID- 23957377
TI  - Effect of cysteine and glutamine added to extender on post-thaw sperm functional
      parameters of buffalo bull.
AB  - Amino acids seem to be crucial components for semen freezing extender due to
      antioxidant properties. Therefore, this study aimed to assess motility
      parameters, membrane integrity, intracellular reactive oxygen species (ROS),
      mitochondrial membrane potential (MMP) and DNA damage to detect the optimum
      concentrations of cysteine and glutamine for buffalo semen cryopreservation.
      Twenty ejaculates of four buffalo bulls were diluted in tris-egg yolk extender
      and divided into seven equal groups consisting of cysteine (5, 7.5 and 10 mmol),
      glutamine (10, 15 and 20 mmol) and no additive. Supplementation of 5 and 7.5 mmol
      cysteine and 15 mmol glutamine in cryopreservation extender significantly
      increased post-thaw motility and plasma membrane integrity of spermatozoa with
      significant reduction in intracellular ROS when compared with control groups (P <
      0.05). Cysteine at 7.5 mmol concentration elevated progressive motility and MMP,
      compared with control (P < 0.05). No significant differences were observed for
      motion patterns and DNA damage of frozen-thawed buffalo spermatozoa in extender
      containing amino acids. The findings of this study showed that supplementation of
      7.5 mmol cysteine and 15 mmol glutamine in semen cryopreservation extender has
      more potential to decrease intracellular ROS, and subsequently elevate motility
      and membrane integrity of buffalo frozen-thawed spermatozoa.

PMID- 23957379
TI  - The efficacy of cognitive prosthetic technology for people with memory
      impairments: a systematic review and meta-analysis.
AB  - Technology can compensate for memory impairment. The efficacy of assistive
      technology for people with memory difficulties and the methodology of selected
      studies are assessed. A systematic search was performed and all studies that
      investigated the impact of technology on memory performance for adults with
      impaired memory resulting from acquired brain injury (ABI) or a degenerative
      disease were included. Two 10-point scales were used to compare each study to an
      ideally reported single case experimental design (SCED) study (SCED scale; Tate
      et al., 2008 ) or randomised control group study (PEDro-P scale; Maher,
      Sherrington, Herbert, Moseley, & Elkins, 2003 ). Thirty-two SCED (mean = 5.9 on
      the SCED scale) and 11 group studies (mean = 4.45 on the PEDro-P scale) were
      found. Baseline and intervention performance for each participant in the SCED
      studies was re-calculated using non-overlap of all pairs (Parker & Vannest, 2009
      ) giving a mean score of 0.85 on a 0 to 1 scale (17 studies, n = 36). A meta
      analysis of the efficacy of technology vs. control in seven group studies gave a
      large effect size (d = 1.27) (n = 147). It was concluded that prosthetic
      technology can improve performance on everyday tasks requiring memory. There is a
      specific need for investigations of technology for people with degenerative
      diseases.

PMID- 23957378
TI  - Redox-neutral alpha-C-H bond functionalization of secondary amines with
      concurrent C-P bond formation/N-alkylation.
AB  - Redox-neutral formation of C-P bonds in the alpha-position of amines was achieved
      via a process that features a combination of an oxidative alpha-C-H bond
      functionalization and a reductive N-alkylation. Benzoic acid functions as an
      efficient catalyst in this three-component reaction of cyclic secondary amines,
      aldehydes and phosphine oxides to provide rapid access to alpha-amino phosphine
      oxides not easily accessible by classic Kabachnik-Fields reactions. 

PMID- 23957380
TI  - Completing the folate biosynthesis pathway in Plasmodium falciparum: p
      aminobenzoate is produced by a highly divergent promiscuous aminodeoxychorismate
      lyase.
AB  - Enzymes that produce or recycle folates are the targets of widely used
      antimalarial drugs. Despite the interest in the folate metabolism of Plasmodium
      falciparum, the molecular identification of ADCL (aminodeoxychorismate lyase),
      which synthesizes the p-aminobenzoate moiety of folate, remained unresolved. In
      the present study, we demonstrate that the plasmodial gene PF14_0557 encodes a
      functional ADCL and report a characterization of the recombinant enzyme. 

PMID- 23957381
TI  - Validation of the Polish version of the EORTC QLQ-CX24 module for the assessment
      of health-related quality of life in women with cervical cancer.
AB  - The aim of our study was to undertake a prospective validation study of the
      Polish version of the EORTC cervical cancer (EORTC QLQ-CX24) module used
      alongside the EORTC core measure. The translated module was pilot-tested
      according to the established EORTC guidelines. Patients with histological
      confirmation of cervical cancer were eligible for the study. All patients filled
      out the Polish version of the EORTC QLQ-CX24 module in addition to EORTC QLQ-C30
      and a demographic questionnaire. Standardised validity and reliability analyses
      were performed. One hundred and seventy-one patients were enrolled into the
      study, mean age +/- SD: 52.1 +/- 9.6. Cronbach alpha coefficients, range 0.81
      0.88, showed positive internal consistency. Re-test was undertaken with 40
      patients (23.4%). Interclass correlations for the EORTC QLQ-CX24 ranged from 0.85
      to 0.89 and proved appropriate test-retest reliability. Satisfactory convergent
      and discriminant validity in multi-trait scaling analyses was seen. Concluding,
      the Polish version of the EORTC QLQ-CX24 module is a reliable and valid tool for
      measuring HRQoL in patients with cervical cancer. It can be fully recommended for
      use in clinical and epidemiological settings in the Polish population. 

PMID- 23957382
TI  - Continuous cerebral spinal fluid drainage associated with complications in
      patients admitted with subarachnoid hemorrhage.
AB  - OBJECT: Cerebral artery vasospasm is a major cause of death and disability in
      patients recovering from subarachnoid hemorrhage (SAH). Although the exact cause
      of vasospasm is unknown, one body of research suggests that clearing blood
      products by CSF drainage is associated with a lower frequency and severity of
      vasospasm. There are multiple approaches to facilitating CSF drainage, but there
      is inadequate evidence to determine the best practice. The purpose of this study
      was to explore whether continuous or intermittent CSF drainage was superior for
      reducing vasospasm. METHODS: The authors performed a randomized clinical trial.
      Within 72 hours of admission for SAH, patients with an external ventricular drain
      (EVD) were randomized to undergo continuous CSF drainage with intermittent
      intracranial pressure (ICP) monitoring (open-EVD group) or continuous ICP
      monitoring with intermittent CSF drainage (monitor-ICP group). RESULTS: After 60
      patients completed the study, an interim analysis was performed. The complication
      rate of 52.9% for the open-EVD group was significantly higher than the 23.1%
      complication rate for the monitor-ICP group (OR 3.75, 95% CI 1.21-11.66, p =
      0.022). These results were reported to the Data Safety and Monitoring Board and
      enrollment was terminated. The odds ratio of vasospasm for the open-EVD versus
      monitor-ICP group was not significant (OR 0.44, 95% CI 0.13-1.45, p = 0.177).
      CONCLUSIONS: Continuous CSF drainage with intermittent ICP monitoring is
      associated with a higher rate of complications than continuous ICP monitoring
      with intermittent CSF drainage, but there is no difference between the two types
      of monitoring in vasospasm. Clinical trial registration no.: NCT01169454
      (clinicaltrials.gov).

PMID- 23957383
TI  - Randomised clinical trial: rabeprazole improves symptoms in patients with
      functional dyspepsia in Japan.
AB  - BACKGROUND: The efficacy of proton pump inhibitors (PPIs) for treating functional
      dyspepsia (FD) is not well established. AIM: This study, named the SAMURAI study,
      aimed to assess the efficacy and dose-response relationship of rabeprazole in
      Japanese patients with FD in a multicentre, double-blinded, randomised, placebo
      controlled trial. METHODS: Investigated FD was diagnosed using the Rome III
      criteria. Subjects who did not respond to 1 week of single-blind placebo
      treatment in a run-in period were randomly assigned to 8 weeks of double-blind
      treatment with rabeprazole 10 mg, 20 mg, 40 mg or placebo, once daily. Dyspeptic
      symptoms were assessed by a dyspepsia symptom questionnaire (7-point Likert
      scale) and symptom diary. RESULTS: Of 392 subjects entered into the run-in
      period, 338 were randomly assigned. Although there was no significant difference
      between placebo and rabeprazole groups in complete symptom relief for four major
      dyspeptic symptoms, the satisfactory symptom relief of rabeprazole 20 mg was
      significantly higher than placebo according to the dyspepsia symptom
      questionnaire (45.3% vs. 28.2%, P = 0.027) and the symptom diary assessment
      (48.7% vs. 30.0%, P = 0.016). The efficacy was not influenced by syndrome type or
      Helicobacter pylori status. No statistically significant differences in the
      incidence of adverse events were seen among treatment groups. CONCLUSIONS:
      Rabeprazole 20 mg once daily but not 10 or 40 mg significantly provides
      satisfactory symptom relief for functional dyspepsia (ClinicalTrials.gov, Number
      NCT01089543).

PMID- 23957384
TI  - High-resolution near-infrared spectroscopy of CH2(+) and its deuterated
      isotopologues.
AB  - Aiming to provide approximate rotational constants for millimeter wave
      spectroscopists to identify the corresponding species in space, we have recorded
      the near-infrared spectra of the methylene cation CH2(+) and its deuterated
      isotopologues, CD2(+) and CHD+, using a high resolution and high sensitivity
      spectrometer. Detection of CH2(+) in space will shed light on interstellar
      chemistry as it is the intermediate between the abundant CH+ and yet to be
      observed CH3(+), which is important in the formation of larger organic molecules.
      CH2(+) and its deuterated isotopologues are also of special interest for
      theoretical studies because of their unique intramolecular dynamics, i.e., the
      Renner-Teller interaction and quasi-linearity. This paper will discuss several
      new bands of CH2(+), the A(0,5[11],0)0 <- X(0,0[0],0)1 and A(0,4[11],0)2 <-
      X(0,0[0],0)1 bands of CD2(+), which have been identified and analyzed, and the
      candidate lines for the A(0,4[10],0)1 <- X(0,0[1],0)0 band of CHD+, in comparison
      with the theoretical predictions by Bunker and colleagues.

PMID- 23957385
TI  - Prevalence, incidence and course of lower extremity injuries in runners during a
      12-month follow-up period.
AB  - To describe the incidence, 12-month prevalence, and course of lower extremity
      injuries that occurred during and after the Amgen Singelloop Breda in 2009. The
      design was based on a prospective cohort study with a population-based setting.
      In total, 3605 registered runners received a web-based baseline questionnaire of
      which 713 participants completed and returned it. Information about previous
      injuries, training programs, and demographic data were gathered at baseline. Site
      and intensity of running injuries and occurrence of new injuries were obtained
      from five post-race questionnaires. The main outcome measurement was lower
      extremity injury. The incidence of running injuries during the Amgen Singelloop
      Breda itself was 7.8%; most of these injuries occurred in the calf muscle, thigh,
      and knee joint. Three-month incidence of injuries during follow-up varied between
      13.5% and 16.3%. During the 12-month follow-up period, 277 new running injuries
      were reported. Runners who ran more than 10 km are more susceptible to injury in
      comparison with runners who ran short distances (10 km or less). In total, 69.1%
      of running injuries resolves within 10 days. Running injuries are very common
      among recreational runners. Injuries mostly occur in the knee, thigh, and calf
      muscle. 

PMID- 23957386
TI  - Models for predicting the ratio of particulate pollutant concentrations inside
      vehicles to roadways.
AB  - Under closed-window driving conditions, the in-vehicle-to-outside (I/O)
      concentration ratio for traffic-related particulate pollutants ranges from nearly
      0 to 1 and varies up to 5-fold across a fleet of vehicles, thus strongly
      affecting occupant exposures. Concentrations of five particulate pollutants
      (particle-bound polycyclic aromatic hydrocarbons, black carbon, ultrafine
      particle number, and fine and coarse particulate masses) were measured
      simultaneously while systematically varying key influential parameters (i.e.,
      vehicle type, ventilation, and speed). The I/O ratios for these pollutants were
      primarily determined by vehicle air exchange rate (AER), with AER being mostly a
      function of ventilation setting (recirculation or outside air), vehicle
      characteristics (e.g., age and interior volume), and driving speed. Small (+/
      0.15) but measurable differences in I/O ratios between pollutants were observed,
      although ratios were highly correlated. This allowed us to build on previous
      studies of ultrafine particle number I/O ratios to develop predictive models for
      other particulate pollutants. These models explained over 60% of measured
      variation, using ventilation setting, driving speed, and easily obtained vehicle
      characteristics as predictors. Our results suggest that I/O ratios for different
      particulate pollutants need not necessarily be measured individually and that
      exposure to all particulate pollutants may be reduced significantly through
      simple ventilation choices. 

PMID- 23957387
TI  - Asymmetric alpha-arylation of amino acid derivatives by Clayden rearrangement of
      ester enolates via memory of chirality.
AB  - A method for asymmetric alpha-arylation of amino acid derivatives has been
      developed. The arylation was performed by Clayden rearrangement of ester enolates
      via memory of chirality to give hydantoins with an aryl-substituted
      tetrasubstituted carbon with up to 99% ee. 

PMID- 23957388
TI  - Powered wheelchairs and scooters for outdoor mobility: a pilot study on costs and
      benefits.
AB  - PURPOSE: This study evaluates the effect of electric powered wheelchairs/scooters
      (PWC/S) on occupational performance, social participation, health and life
      satisfaction. In addition, this study estimates the costs and benefits of PWC/S
      and describes users' experiences with the delivery process. METHODS: This
      prospective study has a before-and-after design. Postal questionnaires were sent
      to 24 first-time PWC/S users before delivery of the PWC/S and 4 months after
      delivery. The participants used their PWC/S for outdoor mobility. RESULTS: PWC/S
      improved the users' daily lives, their ability to engage in mobility-related
      activities and their social participation. For a majority of the users, estimated
      independence, feelings of safety and self-esteem increased although overall
      health and life satisfaction were not significantly affected. All users thought
      that the therapist had considered their needs during the providing process. Most
      participants (73%) were satisfied with their device at follow-up. For the 12
      users who reported no change in health status between measures, the mean societal
      savings based on calculated costs for assistance was ?6227 per person per year.
      CONCLUSIONS: PWC/S seems to improve occupational performance, social
      participation and life satisfaction for users. Moreover, these improvements seem
      to have an economic advantage for both users and society. IMPLICATIONS FOR
      REHABILITATION: The use of a PWC/S has been shown to positively affect a person's
      independence in daily activities which in turn increases the sense of self-esteem
      and security. Facilitating mobility is cost-effective both from a societal as
      well as from anindividual perspective and should be a key intervention in
      rehabilitation.

PMID- 23957389
TI  - Access to hands-on mathematics measurement activities using robots controlled via
      speech generating devices: three case studies.
AB  - PURPOSE: To examine how using a robot controlled via a speech generating device
      (SGD) influences the ways students with physical and communication limitations
      can demonstrate their knowledge in math measurement activities. METHOD: Three
      children with severe physical disabilities and complex communication needs used
      the robot and SGD system to perform four math measurement lessons in comparing,
      sorting and ordering objects. The performance of the participants was measured
      and the process of using the system was described in terms of manipulation and
      communication events. Stakeholder opinions were solicited regarding robot use.
      RESULTS: Robot use revealed some gaps in the procedural knowledge of the
      participants. Access to both the robot and SGD was shown to provide several
      benefits. Stakeholders thought the intervention was important and feasible for a
      classroom environment. CONCLUSIONS: The participants were able to participate
      actively in the hands-on and communicative measurement activities and thus meet
      the demands of current math instruction methods. IMPLICATIONS FOR REHABILITATION:
      Current mathematics pedagogy encourages doing hands-on activities while
      communicating about concepts. Adapted Lego robots enabled children with severe
      physical disabilities to perform hands-on length measurement activities.
      Controlling the robots from speech generating devices (SGD) enabled the children,
      who also had complex communication needs, to reflect and report on results during
      the activities. By using the robots combined with SGDs, children both exhibited
      their knowledge of and experienced the concepts of mathematical measurements.

PMID- 23957390
TI  - Discovery of HIV-1 integrase inhibitors: pharmacophore mapping, virtual
      screening, molecular docking, synthesis, and biological evaluation.
AB  - HIV-1 integrase enzyme plays an important role in the life cycle of HIV and
      responsible for integration of virus into human genome. Here, both computational
      and synthetic approaches were used to design and synthesize newer HIV-1 integrase
      inhibitors. Pharmacophore mapping was performed on 20 chemically diverse
      molecules using DISCOtech, and refinement was carried out using GASP. Ten
      pharmacophore models were generated, and model 2, containing four features
      including two donor sites, one acceptor atom, and one hydrophobic region, was
      considered the best model as it has the highest fitness score. It was used as a
      query in NCI and Maybridge databases. Molecules having more than 99% Q(fit) value
      were used to design 30 molecules bearing pteridine ring and were docked on co
      crystal structure of HIV-1 integrase enzyme. Among these, six molecules, showing
      good docking score compared with the reference standards, were synthesized by
      conventional as well as microwave-assisted methods. All compounds were
      characterized by physical and spectral data and evaluated for in vitro anti-HIV
      activity against the replication of HIV-1 (IIIB) in MT-4 cells. The used approach
      of molecular docking and anti-HIV activity data of designed molecules will
      provide significant insights to discover novel HIV-1 Integrase Inhibitors.

PMID- 23957391
TI  - Barley malt wort fermentation by exopolysaccharide-forming Weissella cibaria MG1
      for the production of a novel beverage.
AB  - AIMS: The growing interest of governments and industry in developing healthy and
      natural alternative foods and beverages that will fulfil the consumer drive
      towards a healthy lifestyle and clean-label, natural diet has led to an increase
      in traditional lactic acid bacteria fermentation research. In particular, this
      research aims to address the organoleptic modulation of beverages using in situ
      produced bacterial polysaccharides. METHODS AND RESULTS: Weissella cibaria MG1 is
      capable of producing exopolysaccharides (dextran) and oligosaccharides
      (glucooligosaccharides) during sucrose-supplemented barley-malt-derived wort
      fermentation. Up to 36.4 g l(-1) of dextran was produced in an optimized system,
      which improved the rheological profile of the resulting fermentate. Additionally,
      small amounts of organic acids were formed, and ethanol remained below 0.5%
      (v/v), the threshold volume for a potential health claim designation.
      CONCLUSIONS: The results suggest that the cereal fermentate produced by W.
      cibaria MG1 could be potentially used for the production of a range of novel,
      nutritious and functional beverages. SIGNIFICANCE AND IMPACT OF THE STUDY: Using
      conventional raw materials and traditional processes, novel LAB-fermented
      beverages can be produced representing an innovative mechanism towards fulfilling
      the aim to decrease government and personal costs as well as potentially
      ameliorating consumer lifestyle regarding dietary-related disease.

PMID- 23957392
TI  - In vivo study of human mandibular distraction osteogenesis. Part II:
      Determination of callus mechanical properties.
AB  - Distraction Osteogenesis (DO) is a surgical technique used to reconstruct bone
      defects. To improve the current treatment protocols, the knowledge of the
      mechanical properties of the bone regenerate is of major interest. The aim of
      this study, constituting the second part of our paper previously published in
      Acta of Bioengineering and Biomechanics, was to identify the elastic and viscous
      properties of bone callus. This is done in the case of a mandibular DO by
      analyzing the experimental measurements of the forces imposed on bone regenerate
      by a distraction device. The bone transport forces were evaluated thanks to
      strain gauges glued on the distraction device. A rheological model describing the
      callus constitutive behavior was developed and the material constants involved
      were identified. The time-dependent character of the bone regenerate mechanical
      behavior was confirmed. The viscous response of the mesenchymal tissue was
      described by two characteristic times. The first one describing the viscoelastic
      callus behavior was estimated to be 140 seconds and the second one representing
      the permanent bone callus lengthening was evaluated to be 5646 seconds. An
      average value of 0.35 MPa for the regenerate Young's modulus was deduced. The
      elastic properties of mesenchymal tissue found are in agreement with the rare
      data available in the literature.

PMID- 23957393
TI  - Protective effect of Cymbopogon citratus on hydrogen peroxide-induced oxidative
      stress in the reproductive system of male rats.
AB  - Cymbopogon citratus (C. citratus) has antioxidant, anti-inflammatory, and
      chemoprotective properties. This study was conducted to evaluate the protective
      effect of C. citratus aqueous extract against hydrogen peroxide (H2O2)-induced
      oxidative stress and injury in the reproductive system of male rats. The twenty
      five rats used in this study were divided into five groups, comprised of five
      rats each. The control group received standard food and drink. The H2O2 group
      received standard food and water with 0.5% H2O2. The rats in the H2O2 + C.
      citratus group and H2O2 + vitamin E group received standard food, H2O2, and C.
      citratus [100 mg.kg(-1) body weight (bw)], or vitamin E as an antioxidant
      reference (500 mg.kg(-1) bw), respectively. The C. citratus group was given C.
      citratus (100 mg.kg(-1) bw) in addition to the standard food and drink. The
      treatments were administered for 30 days. The H2O2 treatment significantly (P <
      0.05) decreased body, testicular, and epididymal weight, as well as glutathione
      (GSH) level, but markedly increased malonaldehyde (MDA) in serum and testes
      homogenates. The rats treated with H2O2 exhibited testicular degeneration and
      significant reduction in sperm viability, motility, count, and rate of normal
      sperm. The C. citratus, vitamin E, and H2O2 treatment significantly (P < 0.05)
      increased the body, testicular, and epididymal weight, testosterone level, the
      values of the various sperm characteristics, and GSH. However, this treatment
      markedly reduced MDA in serum and testes homogenates, as well as testicular
      histopathological alterations in the H2O2-treated rats. The C. citratus aqueous
      extract reduced oxidative stress and protected male rats against H2O2-induced
      reproductive system injury. 

PMID- 23957394
TI  - Collagenase-resistant collagen promotes mouse aging and vascular cell senescence.
AB  - Collagen fibrils become resistant to cleavage over time. We hypothesized that
      resistance to type I collagen proteolysis not only marks biological aging but
      also drives it. To test this, we followed mice with a targeted mutation
      (Col1a1(r/r) ) that yields collagenase-resistant type I collagen. Compared with
      wild-type littermates, Col1a1(r/r) mice had a shortened lifespan and developed
      features of premature aging including kyphosis, weight loss, decreased bone
      mineral density, and hypertension. We also found that vascular smooth muscle
      cells (SMCs) in the aortic wall of Col1a1(r/r) mice were susceptible to stress
      induced senescence, displaying senescence-associated beta-galactosidase (SA
      betaGal) activity and upregulated p16(INK4A) in response to angiotensin II
      infusion. To elucidate the basis of this pro-aging effect, vascular SMCs from
      twelve patients undergoing coronary artery bypass surgery were cultured on
      collagen derived from Col1a1(r/r) or wild-type mice. This revealed that mutant
      collagen directly reduced replicative lifespan and increased stress-induced SA
      betaGal activity, p16(INK4A) expression, and p21(CIP1) expression. The pro
      senescence effect of mutant collagen was blocked by vitronectin, a ligand for
      alphavbeta3 integrin that is presented by denatured but not native collagen.
      Moreover, inhibition of alphavbeta3 with echistatin or with alphavbeta3-blocking
      antibody increased senescence of SMCs on wild-type collagen. These findings
      reveal a novel aging cascade whereby resistance to collagen cleavage accelerates
      cellular aging. This interplay between extracellular and cellular compartments
      could hasten mammalian aging and the progression of aging-related diseases. 

PMID- 23957395
TI  - Evaluating extracellular matrix influence on adherent cell signaling by cold
      trypsin phosphorylation-specific flow cytometry.
AB  - BACKGROUND: Tissue microenvironments comprise different extracellular matrix
      (ECM) proteins that regulate cellular responsiveness to growth factors. In vitro
      culture of adherent cells on ECM-coated substrata is commonly used to study
      microenvironmental influence on specific cell signaling responses.
      Phosphorylation-specific flow cytometry can be utilized to quantify intracellular
      phosphorylation-dependent signaling events in single cells. However this approach
      necessitates trypsinization of adherent cells to accommodate flow cytometric
      analysis. Trypsin is a potent activator of cell signaling and can obscure signal
      transduction events induced by other factors. RESULTS: To address this we
      developed a cold trypsin-phosphorylation-specific flow cytometry protocol, where
      adherent cells are prepared for flow cytometric analysis on ice (~0 degrees C), a
      temperature where trypsin retains activity but where intracellular kinases are
      inactive. We show that this straightforward approach can be used to quantify
      intracellular pERK levels in single adherent primary human vascular smooth muscle
      cells grown on different ECM. CONCLUSIONS: Exploiting the limited temperature
      dependence of trypsin facilitated development of a generally applicable
      phosphorylation-specific flow cytometry method for analysis of adherent cell
      types including primary patient derived cells. We demonstrate the utility of cold
      trypsin-phosphorylation-specific flow cytometry analysis of cell signaling to
      measure microenvironmental influence in single adherent cells.

PMID- 23957396
TI  - Effects of various heat treatments on phenolic profiles and antioxidant
      activities of Pleurotus eryngii extracts.
AB  - Free (FP) and bound phenolics (BP) were extracted from freeze dried (FD), oven
      dried (OD), as well as boiling treated (BT) Pleurotus eryngii samples. Free,
      bound, total phenolics were quantified using Folin-Ciocalteau assay. Qualitative
      and quantitative analysis of phenolic compounds were carried out using high
      performance liquid chromatography (HPLC) coupled with diode array detector (DAD),
      and a total of 8 phenolic compounds were detected. Free phenolic contents
      followed the order: Freeze-dried free phenolics (FDFP) > Oven-dried free
      phenolics (ODFP) > Boiling-treated free phenolics (BTFP), and ranged from 95.42
      (BTFP) to 442.50 (ODPF) MUg gallic acid equivalents (GAE)/g dry weight (DW).
      Bound and total phenolic contents followed the order: FD > OD > BT, and ranged
      from 218.33 (BTBP) to 774.17 (FDBP) and 313.75 (BT total phenolics) to 1090.42
      (FD total phenolics) MUg GAE/g DW. Bound phenolics contributed 49.76% (OD),
      69.59% (BT), and 71% (FD) of the total phenolic contents. All free and bound
      phenolic extracts were investigated for their antioxidant activities by 3
      different assays, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging
      activity, reducing power, and superoxide anion radical scavenging activity. FDFP
      showed strongest DPPH radical scavenging activity (IC50 at 32.61 MUg/mL), ODFP
      showed strongest reducing power (IC50 at 26.31 MUg/mL), and BTBP showed strongest
      superoxide anion radical scavenging activity (IC50 at 14.07 MUg/mL). 

PMID- 23957398
TI  - Suppression of umami aftertaste by polysaccharides in soy sauce.
AB  - Umami is one of 5 basic tastes that make foods savory and palatable. The umami
      aftertaste is a long-lasting taste sensation that is important for Japanese broth
      (dashi) utilized for various Japanese foods. Soy sauce is usually added when
      making dashi-based dishes; however, different soy sauces produce distinct effects
      on the umami aftertaste. In this study, we attempted to identify the substances
      that cause the suppression of the umami aftertaste in soy sauce by combining
      sensory analysis, size fractionation, chemical analysis, and enzymatic treatment.
      The suppressive substance was revealed to be polysaccharides with molecular
      weights between 44900 and 49700. The results of acid hydrolysis and enzymatic
      treatment suggested that the polysaccharides were cellulose. These results
      indicate that a type of water-soluble cellulose derived from soybean, wheat, or
      microorganisms has a suppressive effect on the umami aftertaste of soy sauce.
      Future studies should focus on developing a strategy that regulates the amount of
      these polysaccharides generated during soy sauce production, to maintain or
      enhance the umami aftertaste. 

PMID- 23957397
TI  - Effect of breed on fatty acid composition and lipogenic enzyme abundance in the
      subcutaneous adipose tissue of pigs.
AB  - This study investigated the role of lipogenic enzyme expression in breed-specific
      fat deposition in pigs. OBJECTIVES: (i) determine effect of breed on the relative
      abundance of the key lipogenic enzymes stearoyl-CoA desaturase (SCD), delta-6
      desaturase (Delta6D), and fatty acid synthase (FAS) in pig subcutaneous adipose
      tissue. (ii) Investigate breed-specific relationships between lipogenic enzyme
      abundance and fatty acid composition. Large White * Pietrain, Pietrain, and Duroc
      * Pietrain pigs were used. Expression of SCD, Delta6D, and FAS was analyzed by
      Western blotting. Fatty acid composition was determined by gas chromatography.
      FAS protein in Large White * Pietrain pigs was similar to the Pietrain breed, but
      was significantly higher than Duroc * Pietrain. A positive relationship was found
      between FAS abundance and the saturated fatty acids (SFAs), for Large White *
      Pietrain pigs, but not for the other breeds. Delta6D was significantly higher in
      Large White * Pietrain compared with Duroc * Pietrain and Pietrain. This was
      accompanied by significantly higher total n-3 poly-unsaturated fatty acids
      (PUFAs) in the Large White * Pietrain when compared to the other breeds.
      CONCLUSIONS: (i) increased subcutaneous adipose tissue SFA content in Large White
      * Pietrain pigs (but not Pietrain and Duroc * Pietrain) is related to increased
      abundance of FAS protein; (ii) high n-3 PUFA content in Large White * Pietrain
      pigs is related to activation of Delta6D protein synthesis; (iii) SCD and Delta6D
      abundance does not contribute to between-breed differences in MUFA and n-6 PUFA
      content of pig subcutaneous adipose tissue.

PMID- 23957399
TI  - Effects of water activity on the lipid oxidation and antioxidants of dried laver
      (porphyra) during storage in the dark.
AB  - Lipid oxidation and antioxidant degradation in dried laver (Porphyra) were
      determined during storage at water activities (Aw ) of 0.11, 0.30, 0.51, 0.75, or
      0.89 in the dark at 40  degrees C for 15 d. Lipid oxidation was evaluated by
      measuring peroxide value (POV) and conjugated dienoic acid (CDA) contents, and
      fatty acid composition was analyzed by gas chromatography. Contents of
      polyphenols, tocopherols, and porphyran were determined by spectrophotometry,
      HPLC, and gravimetry, respectively. The POV and CDA contents of the dried laver
      lipids increased during storage as Aw increased from 0.11 to 0.30, 0.51, 0.75,
      and 0.89, whereas the relative content of eicosapentaenoic acid was decreased;
      however, the contents of polyphenols, alpha-tocopherol, and porphyran in dried
      laver showed the reverse phenomena. Lipid oxidation and antioxidant degradation
      in dried laver sharply increased at an Aw of 0.51. Polyphenols, alpha-tocopherol,
      and porphyran contributed to reduction of lipid oxidation in dried laver. The
      degree of lipid oxidation of dried laver was more dependent on the concentration
      of alpha-tocopherol than that of either polyphenols or porphyran during storage
      in the dark. The results strongly suggest that the quality of dried laver can be
      improved by preserving tocopherols as much as possible while decreasing A(w)
      during storage.

PMID- 23957400
TI  - Partial characterization of ultrafiltrated soy protein hydrolysates with
      antioxidant and free radical scavenging activities.
AB  - Soy protein isolate (SPI) was hydrolyzed with Flavourzyme(r) (SHF) or
      chymotrypsin (SHC). Hydrolysates were sequencially fractionated by
      ultrafiltration using different membrane pore sizes (50, 10, and 3 kDa). The
      antioxidant ability of each hydrolysate protein fraction was tested in a liposome
      oxidizing system and their free radical scavenging activity (FRSA) was evaluated
      with the DPPH method (diphenylpicrilhydrazine radical). Molecular weight (MW)
      distribution, solubility, surface hydrophobicity, and amino acid composition of
      each SPI hydrolysate fraction were measured and their effect on antioxidant and
      scavenging activities was established by multivariate correlation. The most
      active ultrafiltrated peptide fractions (P < 0.05), from SHF and SHC, had of MW
      of <3 kDa (F3 and C3, respectively). These fractions decreased liposome oxidation
      by 83.2% and 84.5%, respectively, and also showed the highest FRSA (F3: 21.3% and
      C3: 24.4%). In addition to molecular size, the antioxidant activity and FRSA of
      soy protein fractions were related to their amino acid composition, especially to
      an increased content of Phe and a lowered content of Lys. Also, hydrophobicity of
      ultrafiltrated peptide fractions was an important characteristic (P < 0.001)
      associated with their ability to trap free radicals. Ultrafiltered peptide
      fractions with low MW have a high potential to be used as natural alternatives to
      prevent lipid oxidation in foods. 

PMID- 23957401
TI  - Physicochemical characterization and antioxidant activity of commercial
      Portuguese honeys.
AB  - The present study evaluated the physicochemical characteristics and antioxidant
      activity of 13 commercial honeys from diverse floral origin, produced in
      Portugal. The values of electrical conductivity of cardoon and pennyroyal honeys
      were superior to the maximum limits defined by European legislation. Citrus,
      strawberry tree, and 1 sample of lavender honeys had values of diastase activity
      below those determined by European legislation. Strawberry tree, pennyroyal, and
      cardoon honeys had the highest amounts of potassium that coincided with the
      highest electrical conductivity. Strawberry tree honey was the most effective as
      antioxidant along with cardoon and heather honeys. This ability was strongly
      correlated with the amounts of phenols and flavonoids and not with the levels of
      vitamin C or proline. 

PMID- 23957402
TI  - Peel effects on phenolic composition, antioxidant activity, and making of
      pomegranate juice and wine.
AB  - Pomegranate peel was used in juicing to find out its effects on the juice
      products' (storable juice and wine) sensory property, polyphenols composition,
      and antioxidant ability. Macroporous resin was used to purify the polyphenols,
      and 6 different in vitro assays were used to comprehensively determine the
      antioxidant activity of each. The results showed that juicing with peel made the
      juice bitter and astringent, but contributed better sensory quality to wine. Peel
      contributed higher total polyphenols and flavonoids, but lower anthocyanins to
      the juice products, and caused the phenolics content to fluctuate more
      dramatically during making wine than the storable juice. Polyphenols purified
      from the juice products containing peel showed higher total reducing ability and
      2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6
      sulfonic acid radical elimination abilities, but their clearance activity of
      hydroxyl radicals was not positive, and their superoxide anion radical
      elimination ability showed no significant difference when compared to polyphenols
      purified from juice products without peel. 

PMID- 23957403
TI  - Identification and analysis of the constituents in an aqueous extract of
      Tricholoma matsutake by HPLC coupled with diode array detection/electrospray
      ionization mass spectrometry.
AB  - The main constituents in an aqueous extract of Tricholoma matsutake (Tm) were
      identified by high-performance liquid chromatography coupled with diode array
      detection and electrospray ionization time-of-flight mass spectrometry (HPLC
      DAD/TOF-MS) and ion trap mass spectrometry (HPLC-DAD/Trap-MSn). The main factors
      in the extraction process which affect the yields of nutrients were optimized by
      single-factor experiments and orthogonal experiment design. In total, 12
      constituents were identified from the aqueous extract of Tm, including tyrosine,
      cytidine, uridine, eritadenine, phenylalanine, nicotinamide, inosine, guanosine,
      tryptophan, adenosine, 5'-deoxy-5'-methylthioadenosine and riboflavin. The
      optimized extraction conditions were: the ratio of water to sample was 10 : 1
      (v/w), Tm was extracted by ultrasonic-assisted extraction for 10 min, followed by
      water bath heating at 60  degrees C for 1 h. Among these extraction factors, the
      heating temperature is significant based on analysis of variance (ANOVA). The
      yields of nutrients were affected dramatically at high temperature leading to the
      loss of nutrients, especially for nucleosides and some amino acids. 

PMID- 23957406
TI  - It was a very good year.

PMID- 23957404
TI  - Inactivation of polyphenoloxidase by pulsed light.
AB  - The effect of pulsed light on the inactivation of polyphenoloxidase (PPO) in
      model solutions was investigated focusing on the effect of enzyme concentration
      and total energy dose of the treatment. PPO inactivation increased with the dose
      of the treatment. Complete enzyme inactivation was achieved by pulsed light doses
      higher than 8.75 J cm(-2) . At low PPO concentrations (4 to 10 U), the enzyme
      resulted highly inactivated by pulsed light treatment. Further increase in enzyme
      units determined a progressive decrease in PPO inactivation. The latter was
      attributed to protein structural modifications including cleavage and
      unfolding/aggregation phenomena. PPO amounts higher than 10 U probably favoured
      enzyme conformations that were less prone to intermolecular rearrangements
      leading to inactivation. 

PMID- 23957407
TI  - Effects of antimicrobial coatings and cryogenic freezing on survival and growth
      of Listeria innocua on frozen ready-to-eat shrimp during thawing.
AB  - Foodborne pathogens such as Listeria monocytogenes could pose a health risk on
      frozen ready-to-eat (RTE) shrimp as the pathogen could grow following thawing. In
      this study, antimicrobial-coating treatments alone, or in combination with
      cryogenic freezing, were evaluated for their ability to inhibit the growth of
      Listeria innocua, a surrogate for L. monocytogenes, on RTE shrimp. Cooked RTE
      shrimp were inoculated with L. innocua at 3 population levels and treated with
      coating solutions consisting of chitosan, allyl isothiocyanate (AIT), or lauric
      arginate ester (LAE). The treated shrimp were then stored at -18  degrees C for 6
      d before being thawed at 4, 10, or 22  degrees C for either 24 or 48 h. Results
      revealed that antimicrobial coatings achieved approximately 5.5 to 1 log CFU/g
      reduction of L. innocua on RTE shrimp after the treatments, depending on the
      inoculated population levels. The coating-treated shrimp samples had
      significantly (P < 0.05) less L. innocua than controls at each thawing
      temperature and time. Cryogenic freezing in combination with coating treatments
      did not achieve synergistic effects against L. innocua. Antimicrobial coatings
      can help to improve product safety by reducing Listeria on RTE shrimp. 

PMID- 23957408
TI  - Frequency and correlation of some enteric indicator bacteria and Salmonella in
      ready-to-eat raw vegetable salads from Mexican restaurants.
AB  - Data about Salmonella presence in ready-to-eat raw vegetable salads (REVS)
      consumed in restaurants or sold as REVS in Mexico is not available. The objective
      of the study was to measure the frequency of coliform bacteria (CB), fecal
      coliform (FC), Escherichia coli, and Salmonella in REVS from different types of
      restaurants and determine the correlations of CB, FC, and E. coli versus
      Salmonella from frequencies and concentration data. The REVS were purchased from
      3 types of restaurants: national chain restaurants (A1 , A2 ); local restaurants
      (B1 , B2 ); and small restaurants in local markets (C1 , C2 , C3 ). Two
      restaurants for each A and B, and 3 for C, were included. Forty REVS were
      purchased at each A and B restaurant, and 20 at each C restaurant. CB were tested
      by plate count using violet red bile agar, FC and E. coli were detected by the
      most probable number method and E. coli confirmed using IMViC test; conventional
      method of culture was used for Salmonella. Of 220 analyzed samples, 100% had CB,
      95.5% had FC, 83.2% had E. coli, and 6.8% had Salmonella. E. coli frequency was
      equal to or exceeded 75% in all the cases: 75% (A1 , C1 , C2 ), 80% (B2 ), 85%
      (B1 , C3 ), and 100% (A2 ). Salmonella frequency was equal to or exceeded 2.5% in
      all cases: 2.5% (A1 ), 5% (B2 , C2 ), 7.5% (B1 ), and 10% (A2 , C1 , C3 ). No
      correlation was observed between FC or E. coli versus Salmonella in the analyzed
      salads. All the tested salads were of poor quality microbiologically, and
      microbiological quality did not differ between the restaurants types. 

PMID- 23957409
TI  - Influence of yeasts on the oil quality indexes of table olives.
AB  - After moisture, fat is the major constituent of table olives. However, scarce
      studies have been carried out to determine the influence of microorganisms and
      type of processing on the modification of their quality indexes. The present
      survey studies the influence of lipolytic (Candida boidinii TOMC Y5 and
      Wickerhamomyces anomalus TOMC Y10) and nonlipolytic (Debaryomyces etchellsii TOMC
      Y9 and Pichia galeiformis TOMC Y27) yeasts on the oil quality indexes of
      Manzanilla and Hojiblanca green fruits processed as directly brined and lye
      treated table olives. Overall, the inocula scarcely used available sugars, except
      the lipolytic C. boidinii strain in lye-treated olives. Acetic acid production
      was limited in all conditions, except for the D. etchellsii strain in directly
      brined Manzanilla fruits. Ethanol formation was also reduced, although the W.
      anomalus (in both types of elaboration) and the C. boidinii (in lye-treated
      olives) strains produced significantly higher proportions. Apparently, changes in
      the oil quality indexes of processed olives were not related to the presence of
      yeasts, and hence, could have been caused by the endogenous activity of the
      fruits. A principal component analysis using the microbiological,
      physicochemical, and oil quality data supported this hypothesis, grouping
      treatments according to olive variety and type of elaboration, while segregation
      due to yeast inocula was not observed. 

PMID- 23957410
TI  - Predominant bacteria diversity in Chinese traditional sourdough.
AB  - The purpose of this study was to identify the major bacteria in Chinese
      traditional sourdough (CTS). Five CTS samples (Hn-87, Sx-91, Gs-107, Hf-112, and
      Hr-122) were collected from different Chinese steamed breads shops or private
      households. The total bacterial DNA was extracted from sourdough samples and
      sequenced using Illumina Hiseq 2000 system. Illumina tags were assigned to BLASTN
      server based on 16S rRNA libraries to reveal a genetic profile. Phylogenetic
      analysis revealed that the bacteria in traditional sourdough samples were
      dominated by the genera Leuconostoc and Lactobacillus. Beta diversity analysis,
      principal component analysis, and cluster analysis compared the bacterial
      differences in traditional sourdough samples. The results showed that
      Leuconostoc, Lactobacillus, and Weissella were the predominant genera among the 5
      samples. This differentiated the sourdoughs into 3 typologies, namely, 1) Gs-107
      and Sx-91, 2) Hr-122 and Hn-87, and 3) Hf-112. This study identified 3 unique
      major bacteria genus in CTS bread ecosystems. 

PMID- 23957411
TI  - Microbiological and fermentative properties of baker's yeast starter used in
      breadmaking.
AB  - This study assessed the levels of microbial contaminants in liquid, compressed
      and dry commercial baker's yeasts used as starters in breadmaking. Eumycetes,
      Enterobacteriaceae, total and fecal coliforms, Bacillus spp., and lactic acid
      bacteria (LAB), in particular enterococci, were quantified. Results obtained in
      this study highlighted that baker's yeast could represent a potential vehicle of
      spoilage and undesirable microorganisms into the baking environment, even if
      these do not influence the leavening activity in the dough, as ascertained by
      rheofermentometer analysis. Different microbial groups, such as spore-forming
      bacteria and moulds, were found in baker's yeast starters. Moreover, different
      species of LAB, which are considered the main contaminants in large-scale yeast
      fermentations, were isolated and identified by Denaturing Gradient Gel
      Electrophoresis (DGGE) and 16S rDNA sequencing. The most recurrent species were
      Lactobacillus plantarum, Enterococcus faecalis, and Enterococcus durans, isolated
      from both compressed and dry starters, whereas strains belonging to Leuconostoc
      and Pediococcus genera were found only in dry ones. Nested-Polymerase Chain
      Reaction (Nested-PCR) and Randomly Amplified Polymorphic DNA-PCR (RAPD-PCR) were
      also used to highlight the biodiversity of the different commercial yeast
      strains, and to ascertain the culture purity. 

PMID- 23957412
TI  - Impact of rearing conditions on the microbiological quality of raw retail poultry
      meat.
AB  - There is a gap in knowledge of microbiological quality in raw chicken products
      produced by nonconventional methods and no studies have reported the
      microbiological quality of turkeys produced under different rearing environments.
      Thus, the aim of this study was to compare the microbiological quality of
      conventionally and organically reared whole chicken and turkey carcasses
      purchased from 3 retail outlets in Knoxville, Tenn., U.S.A. A total of 100 raw
      broiler chickens organically (n = 50) and 50 raw turkey carcasses consisting of 3
      brands reared either conventionally (n = 25) or organically (n = 25) were
      evaluated. The FDA BAM protocol for rinsing poultry carcasses was used to
      enumerate of aerobic bacteria, Campylobacter, and Staphylococcus spp., and for
      qualitative analysis of Salmonella. Organic chickens from one brand had the
      highest average counts of aerobic bacteria, Staphylococcus spp. and Campylobacter
      (4.8, 4.8, and 4.7 Log10 CFU/mL rinsate, respectively) while the other organic
      brand had the lowest average counts (3.4, 3.3, and 3.1, respectively) of all 4
      brands evaluated. The organic turkeys had the highest average counts of these
      same bacteria (4, 3.9, and 3.8, respectively) compared to the 2 brands of
      conventional turkeys evaluated. Salmonella (5% prevalence) was isolated only from
      organic chickens and turkeys. From these data, it appears that the
      microbiological quality of the raw product was not dependent on rearing
      conditions and, thus, it cannot be assumed that organic raw poultry is safer than
      conventionally raised poultry in terms of microbiological quality. 

PMID- 23957413
TI  - Combined effect of dimethyl dicarbonate (DMDC) and nisin on indigenous
      microorganisms of litchi juice and its microbial shelf life.
AB  - The individual and combined influences of dimethyl dicarbonate (DMDC) and nisin
      (200 IU/mL) at mild heat on the inactivation of indigenous microorganisms in
      litchi juice, including bacteria, molds and yeasts (M&Y), were investigated. The
      fresh litchi juice with or without nisin were exposed to 250 mg/L DMDC at 30, 40,
      or 45  degrees C for 0.5, 1, 2, 3, 4, or 6 h. A complete inactivation of M&Y in
      the litchi juice with or without nisin was achieved as exposed to 250 mg/L DMDC
      at 30, 40, or 45  degrees C for 0.5 h. The bacteria, especially Bacillus sp. and
      Leuconstoc mesenteroides showed higher resistance than M&Y in the litchi juice.
      Bacillus sp. and Leuconstoc mesenteroides in the litchi juice was not completely
      inactivated by 250 mg/L DMDC at 30, 40, or 45  degrees C. However, nisin addition
      can enhanced the inactivation of these bacteria by DMDC, and nisin and DMDC also
      showed a synergistic effect on the inactivation of bacteria. M&Y and bacteria
      were not detected in the litchi juice added with 200 IU/mL nisin as exposed to
      250 mg/L DMDC at 45  degrees C for 3 h. In addition, microbial shelf life of the
      litchi juice during storage at 4  degrees C also was evaluated as treated by 250
      mg/L DMDC or combination with nisin at 45  degrees C for 3 h. 

PMID- 23957414
TI  - Antimicrobial activity of a pullulan-caraway essential oil coating on reduction
      of food microorganisms and quality in fresh baby carrot.
AB  - This research evaluated the antimicrobial efficacy of pullulan films containing
      caraway essential oil (CEO). The films were prepared from a 10% of pullulan,
      containing from 0.12% to 10.0% of CEO. The composition of the CEO was analyzed
      with the use of gas chromatography. The antimicrobial activity of the CEO was
      evaluated with the method of serial microdilutions, and the films containing CEO
      with the agar diffusion method against selected Gram-negative, Gram-positive
      bacteria, and fungi. The structure of the film surface and its cross-section were
      analyzed using a scanning electron microscope (SEM). Analyses were also carried
      out to determine the efficacy of a pullulan coating with 10% CEO on baby carrots
      experimentally inoculated with Salmonella enteritidis, Staphylococcus aureus,
      Saccharomyces cerevisiae, or Aspergillus niger and stored at a room temperature
      for 7 d. At a concentration of 0.12%, CEO inhibited the growth of all the tested
      microorganisms. Pullulan films containing 8% to 10% of CEO were active against
      all tested microorganisms. Populations of S. aureus on carrot samples were
      reduced by approximately 3 log CFU/g, while those of A. niger and S. cerevisiae
      by, respectively, 5 and 4 log CFU/g, after 7 d of storage. S. enteritidis was the
      most resistant among the tested species, since it was not significantly reduced
      after 7 d of storage. At the end of storage, samples treated with pullulan
      caraway oil coating maintained better visual acceptability than control samples.
      Results of this study suggest the feasibility of applying a pullulan film with
      incorporated CEO to extend the microbiological stability of minimally processed
      foods. 

PMID- 23957415
TI  - Bacterial and fungal communities in Pu'er tea samples of different ages.
AB  - Pu'er is a major kind of postfermented tea and is made with a "large leaf"
      variety of Camellia sinensis (C. sinensis assamica), whose distribution is
      limited to the mountains of southern Yunnan, China. The quality of Pu'er tea is
      believed to increase with storage (aging, maturing) because of postfermentation
      by microbes. The effect of storage period (from < 1 to 192 mo) on the bacteria
      and fungi in Pu'er tea was investigated by a culture-dependent and a PCR-DGGE
      method. The individual numbers of fungi and bacteria decreased with increasing
      storage time and were significantly greater in ripened tea than in raw Pu'er tea.
      Both methods indicated that yeast, Aspergillus spp., and Penicillium spp. were
      the dominant fungi in almost all the samples. However, the common bacteria
      detected by the culture-dependent method were species of Pseudomonas,
      Achromobacter, Alcaligenes, Sporosarcina, and Bacillus, whereas those detected by
      PCR-DGGE were species of Staphylococcus, Arthrobacter, and Streptomyces.
      According to ordination analysis, bacterial community structure differed between
      ripened and raw Pu'er tea. Bacterial diversity was positively correlated with
      aging time, while fungal diversity in both raw and ripened tea increased during
      the first 60 mo of aging and then decreased. Changes in polyphenol content were
      correlated with the changes in fungal diversity. These results suggest that the
      relationship between storage time and the quality of Pu'er tea is complex and
      involves changes in polyphenol content and microbial abundance and diversity. 

PMID- 23957416
TI  - Preparation methods for monodispersed garlic oil microspheres in water using the
      microemulsion technique and their potential as antimicrobials.
AB  - Garlic oil is considered as a natural broad-spectrum antibiotic because of its
      well-known antimicrobial activity. However, the characteristics of easy
      volatility and poor aqueous solubility limit the application of garlic oil in
      industry. The purpose of the present work is to develop and evaluate an oil-free
      microemulsion by loading garlic oil in microemulsion system. Microemulsions were
      prepared with ethoxylated hydrogenated castor (Cremophor RH40) as surfactant, n
      butanol (or ethanol) as cosurfactant, oleic acid-containing garlic oil as oil
      phase, and ultrapure water as water phase. The effects of the ratio of surfactant
      to cosurfactant and different oil concentration on the area of oil-in-water (O/W)
      microemulsion region in pseudoternary phase diagrams were investigated. The
      particle size and garlic oil encapsulation efficiency of the formed
      microemulsions with different formulations were also investigated. In addition,
      the antimicrobial activity in vitro against Escherichia coli and Staphylococcus
      aureus was assessed. The experimental results show that a stable microemulsion
      region can be obtained when the mass ratio of surfactant to cosurfactant is,
      respectively, 1:1, 2:1, and 3:1. Especially, when the mixture surfactants of
      RH40/n-butanol 2/1 (w/w) is used in the microemulsion formulation, the area of
      O/W microemulsion region is 0.089 with the particle size 13.29 to 13.85 nm and
      garlic oil encapsulation efficiency 99.5%. The prepared microemulsion solution
      exhibits remarkable antibacterial activity against S. aureus. 

PMID- 23957417
TI  - Food security and cardioprotection: the polar lipid link.
AB  - The projected increase in world population and therefore demand for food in the
      foreseeable future pose some risks on how secure is the food production system
      today. Millions of people are threatened by malnutrition, cardiovascular diseases
      (CVDs), diabetes, and obesity. This is a multidimensional challenge: the
      production of food needs to be increased but also the quality of food needs to be
      improved so less people suffer from undernourishment and CVDs. This hypothesis
      paper addresses this problem by critically evaluating recent developments on the
      role of food components against CVDs, presenting recent insights for assessing
      the nutritional value of food and suggesting novel approaches toward the
      sustainable production of food that would, in turn, lead to increased food
      security. The issue of the sustainability of lipid sources and genetically
      modified crops is also discussed from a food security point of view. 

PMID- 23957418
TI  - Use of whey protein soluble aggregates for thermal stability-a hypothesis paper.
AB  - Forming whey proteins into soluble aggregates is a modification shown to improve
      or expand the applications in foaming, emulsification, gelation, film-formation,
      and encapsulation. Whey protein soluble aggregates are defined as aggregates that
      are intermediates between monomer proteins and an insoluble gel network or
      precipitate. The conditions under which whey proteins denature and aggregate have
      been extensively studied and can be used as guiding principles of producing
      soluble aggregates. These conditions are reviewed for pH, ion type and
      concentration, cosolutes, and protein concentration, along with heating
      temperature and duration. Combinations of these conditions can be used to design
      soluble aggregates with desired physicochemical properties including surface
      charge, surface hydrophobicity, size, and shape. These properties in turn can be
      used to obtain target macroscopic properties, such as viscosity, clarity, and
      stability, of the final product. A proposed approach to designing soluble
      aggregates with improved thermal stability for beverage applications is
      presented. 

PMID- 23957419
TI  - Sensory profiles for dried fig (Ficus carica L.) cultivars commercially grown and
      processed in California.
AB  - A trained sensory panel evaluated the 6 fig cultivars currently sold in the
      California dried fig market. The main flavor and aroma attributes determined by
      the sensory panel were "caramel," "honey," "raisin," and "fig," with additional
      aroma attributes: "common date," "dried plum," and "molasses." Sensory
      differences were observed between dried fig cultivars. All figs were processed by
      2 commercial handlers. Processing included potassium sorbate as a preservative
      and SO2 application as an antibrowning agent for white cultivars. As a
      consequence of SO2 use during processing, high sulfite residues affected the
      sensory profiles of the white dried fig cultivars. Significant differences
      between dried fig cultivars and sources demonstrate perceived differences between
      processing and storage methods. The panel-determined sensory lexicon can help
      with California fig marketing. 

PMID- 23957420
TI  - Quality of dry-cured ham compared with quality of dry-cured shoulder.
AB  - The physicochemical and sensory properties of 30 dry-cured hams and 30 dry-cured
      shoulders were analyzed to determine the relationships between them. The
      variables used to characterize both products were: compositional parameters,
      instrumental texture, amino acid and fatty acid composition, and sensory profile.
      Despite being products from the same animal and composed mainly of fat, lean, and
      bone, their morphological differences determine the conditions of the processing
      time, which produced differences between products in most of the parameters
      evaluated. Dry-cured shoulders showed lower moisture content and greater
      instrumental hardness due to their morphology and muscular structure. Besides,
      these samples showed lower amino acid content according to the shorter ripening
      time. For the same reason, the dry-cured hams showed higher moisture content,
      lower instrumental hardness, and higher amino acid content. However, the
      differences in the muscular structure did not affect the sensory characteristics,
      which were more related with some compositional parameters, such as chloride,
      moisture, and amino acid content and with the length of the curing process. 

PMID- 23957421
TI  - Sensory properties of under-roasted coffee beverages.
AB  - Conditions milder than standard roasting (under-roasting: 140 to 170  degrees C
      for 20 to 12 min) have been proposed to reduce the formation of potentially
      harmful compounds developing during standard coffee roasting. In the present
      study, sensory properties of brews prepared with under-roasted coffees (140 to
      165  degrees C for 20 min) were described by descriptive analysis. Two meta
      attributes were defined: "coffee" consisting of attributes positively related to
      the increasing of process temperature and "no-coffee" consisting of those
      negatively related to temperature. The progressive lowering of "no-coffee" and
      the corresponding increasing of "coffee" mean values were induced by temperature
      increasing in under-roasting conditions. The processing temperature of 150 
      degrees C seems to represent the changing point between the 2 meta-attributes
      with "no-coffee" prevailing at lower and "coffee" at higher temperatures.
      Consumer responses indicate the positive effect of both product processing
      temperature and "coffee" attribute intensity on liking. Brews from coffee treated
      at temperature lower than 150  degrees C showed a sensory profile characterized
      by "no-coffee" attributes and resulted the less preferred by regular coffee
      consumers. 

PMID- 23957422
TI  - Content and bioaccessibility of aluminium in duplicate diets from southern Spain.
AB  - Aluminium is found naturally in foods and beverages, but levels increase notably
      during processing, packaging, storage, and cooking, as a consequence of its
      presence in food additives and the wide use of aluminium utensils and vessels.
      Dietary intake of Al was estimated in 2 population groups in southern Spain
      (families and university students) in a duplicate diet sampling study. Diets were
      sampled for 7 consecutive days, and Al was determined in acid-mineralized samples
      with electrothermal atomization-atomic absorption spectrometry (ETA-AAS). Mean
      values for Al intake were 2.93 and 1.01 mg/d in families and students,
      respectively, ranging from 0.12 to 10.00 mg/d. Assuming an average adult weight
      of 60 kg, the mean dietary exposures to aluminium were 0.34 and 0.12 mg/kg body
      weight/week in these groups, which amounted to 17% and 6% of the 2 mg/kg body
      weight estimated as the tolerable weekly intake by the Joint FAO/WHO Expert
      Committee on Food Additives. Bioaccessibility of dietary Al tested with in vitro
      studies ranged from 0.30 to 17.26% (absorbable fraction). The highest aluminium
      intakes were observed in subjects consuming diets with a low adherence to the
      Mediterranean diet, which were associated to high consumption of processed and
      canned food. On the contrary, subjects consuming diets with a high adherence to
      the Mediterranean diet patterns showed the lowest Al intakes. The present
      findings are useful for giving both a reliable estimate of total aluminium
      dietary intake and tolerable intake levels according to usual dietary habits. 

PMID- 23957423
TI  - Fluorescence imaging spectroscopy (FIS) for comparing spectra from corn ears
      naturally and artificially infected with aflatoxin producing fungus.
AB  - In an effort to address the problem of rapid detection of aflatoxin in grain,
      particularly oilseeds, the current study assessed the spectral differences of
      aflatoxin production in kernels from a cornfield inoculated with spores from 2
      different strains of toxigenic Aspergillus flavus. Aflatoxin production in corn
      from the same field due to natural infestation was also assessed. A small corn
      plot in Baton Rouge, La., U.S.A., was used during the 2008-growing season. Two
      groups of 400 plants were inoculated with 2 different inocula and 1 group of 400
      plants was designated as controls. Any contamination detected in the controls was
      attributed to natural infestation. A subset of each group was imaged with a
      visible near infra red (VNIR) hyperspectral system under ultra violet (UV)
      excitation and subsequently analyzed for aflatoxin using affinity column
      fluorometry. Group differences were statistically analyzed. Results indicate that
      when all the spectral data across all groups were averaged, any potential
      differences between groups (treated and untreated) were obscured. However,
      spectral analysis based on contaminated "hot" pixel classification showed a
      distinct spectral shift/separation between contaminated and clean ears with
      fluorescence peaks at 501 and 478 nm, respectively. All inoculated and naturally
      infected control ears had fluorescence peaks at 501 nm that differed from
      uninfected corn ears. Results from this study may be useful in evaluating rapid,
      noninvasive instrumentation and/or methodology for aflatoxin detection in grain. 

PMID- 23957424
TI  - Asymmetric total synthesis of neoxaline.
AB  - A first asymmetric total synthesis and determination of the absolute
      configuration of neoxaline has been accomplished through the highly
      stereoselective introduction of a reverse prenyl group to create a quaternary
      carbon stereocenter using (-)-3a-hydroxyfuroindoline as a building block,
      construction of the indoline spiroaminal via cautious stepwise oxidations with
      cyclizations from the indoline, assembly of (Z)-dehydrohistidine, and
      photoisomerization of unnatural (Z)-neoxaline to the natural (E)-neoxaline as the
      key steps. 

PMID- 23957425
TI  - The clinicopathologic significance of endothelial tubuloreticular inclusions in
      glomerular diseases.
AB  - BACKGROUND: The presence of tubuloreticular inclusions (TRIs) in endothelial
      cells (ECs) always evokes suspicion of an association with underlying viral
      infections or autoimmune diseases. However, other underlying diseases can be
      associated with TRI expression. Since identification of the underlying disease is
      of primary consideration for management of glomerulonephritis (GN), it is
      important to clarify the clinical significance of TRI expression. METHODS: The
      authors studied 104 renal biopsy cases having TRI. They investigated their
      clinicopathological profiles and focused on potential connections with underlying
      diseases. RESULTS: Among 104 renal biopsy cases, 62 cases (59.6%) were associated
      with lupus nephritis (LN) and 20 cases (19.2%) were associated with a viral
      infection (hepatitis B virus (13), hepatitis C virus (4), and human
      immunodeficiency virus (3)). Other underlying disease groups included membranous
      GN (MGN) (7), IgA nephropathy (7), Henoch-Schoenlein purpura (HSP) nephritis (2),
      and others (6). The incidence of TRIs in both LN and viral infections was
      significantly higher than for other diseases (p < 0.0001). Among 7 MGN cases, 2
      cases were diabetes, 1 case was associated with lung cancer, another case with
      antineutrophilic cytoplasmic antibody (ANCA), and the others showed no evidence
      of systemic disease. On immunofluorescence (IF) study, 2 MGN cases, 2 IgA
      nephropathy cases, and 1 HSP nephritis case showed C1q deposition, with no
      evidence of SLE. CONCLUSIONS: TRIs were identified in MGN and other glomerular
      diseases, including IgA nephropathy and HSP nephritis. However, a diagnosis of LN
      should be considered because TRIs associated with a full-house IF pattern are
      usually found in LN.

PMID- 23957426
TI  - Identification of cryptotanshinone as an inhibitor of oncogenic protein tyrosine
      phosphatase SHP2 (PTPN11).
AB  - Activating mutations of PTPN11 (encoding the SHP2 phosphatase) are associated
      with Noonan syndrome, childhood leukemias, and sporadic solid tumors. Virtual
      screening combined with experimental assays was performed to identify inhibitors
      of SHP2 from a database of natural products. This effort led to the
      identification of cryptotanshinone as an inhibitor of SHP2. Cryptotanshinone
      inhibited SHP2 with an IC50 of 22.50 MUM. Fluorescence titration experiments
      confirmed that it directly bound to SHP2. Enzymatic kinetic analyses showed that
      cryptotanshinone was a mixed-type and irreversible inhibitor. This drug was
      further verified for its ability to block SHP2-mediated cell signaling and
      cellular functions. Furthermore, mouse myeloid progenitors and patient leukemic
      cells with the activating mutation E76K in PTPN11 were found to be sensitive to
      this inhibitor. Since cryptotanshinone is used to treat cardiovascular diseases
      in Asian countries, this drug has a potential to be used directly or to be
      further developed to treat PTPN11-associated malignancies. 

PMID- 23957427
TI  - An atypical case of herpes simplex virus endotheliitis presented as bullous
      keratopathy.
AB  - PURPOSE: To present an atypical case of herpes simplex virus (HSV) endotheliitis.
      METHODS: The authors report the case of a 62-year-old female patient who
      presented with unilateral diffuse corneal edema with Descemet's membrane folds
      and bullae, without keratic precipitates, iritis, significant anterior chamber
      reaction, or intraocular pressure (IOP) elevation. The patient had no documented
      positive history of ocular surgery and no abnormal findings were present in the
      fellow eye. Endotheliitis of viral origin was suspected and Goldmann-Witmer
      coefficient for HSV, cytomegalovirus, and varicela zoster virus was calculated.
      RESULTS: Goldmann-Witmer coefficient was positive for HSV. Treatment with oral
      valacyclovir and topical dexamethasone resulted in complete resolution of corneal
      edema within 1 week. CONCLUSIONS: HSV endotheliitis can present with bullous
      keratopathy as the only clinical manifestation, without typical findings such as
      keratic precipitates, iritis, and IOP elevation.

PMID- 23957428
TI  - Palladium-catalyzed alkyne insertion/reduction route to trisubstituted olefins.
AB  - A new route to trisubstituted olefins through a palladium-catalyzed alkyne
      insertion/reduction reaction with unactivated alkyl iodides is reported. The
      reaction proceeds under mild conditions and tolerates a range of functional
      groups and substitution patterns. Preliminary mechanistic inquiry suggests that
      the transformation may proceed through a hybrid radical/organometallic pathway. 

PMID- 23957429
TI  - Identification, characterisation and molecular modelling of two AP endonucleases
      from base excision repair pathway in sugarcane provide insights on the early
      evolution of green plants.
AB  - Unlike bacteria and mammals, plant DNA repair pathways are not well
      characterised, especially in monocots. The understanding of these processes in
      the plant cell is of major importance, since they may be directly involved in
      plant acclimation and adaptation to stressful environments. Hence, two sugarcane
      ESTs were identified as homologues of AP endonuclease from the base-excision
      repair pathway: ScARP1 and ScARP3. In order to understand their probable function
      and evolutionary origin, structural and phylogenetic studies were performed using
      bioinformatics approaches. The two predicted proteins present a considerable
      amino acid sequence similarity, and molecular modelling procedures indicate that
      both are functional, since the main structural motifs remain conserved. However,
      inspection of the sort signal regions on the full-length cDNAs indicated that
      these proteins have a distinct organelle target. Furthermore, variances in their
      promoter cis-element motifs were also found. Although the mRNA expression pattern
      was similar, there were significant differences in their expression levels. Taken
      together, these data raise the hypothesis that the ScARP is an example of a
      probable gene duplication event that occurred before monocotyledon/dicotyledon
      segregation, followed by a sub-functionalisation event in the Poaceae, leading to
      new intracellular targeting and different expression levels.

PMID- 23957430
TI  - Inflammatory myofibroblastic tumour of the lung with a novel PPFIBP1-ALK fusion
      variant.

PMID- 23957431
TI  - Fournier's gangrene of the penis caused by Streptococcus dysgalactiae subspecies
      equisimilis: case report and incidence study in a tertiary-care hospital.
AB  - BACKGROUND: Fournier's gangrene is a rare necrotizing soft tissue infection of
      the scrotum and penis. We report, to our knowledge, the first case of Fournier's
      gangrene caused by Streptococcus dysgalactiae subsp. equisimilis (SDSE), a strain
      of pyogenic beta-hemolytic streptococci that is increasingly being recognized as
      an important human pathogen. CASE PRESENTATION: We describe a healthy 59 year-old
      Caucasian male who presented to the emergency department with Fournier's gangrene
      of the penis and scrotum, with extension to the anterior abdominal wall. He
      underwent urgent surgical debridement of his scrotum, penis, and anterior
      abdomen. Swabs from the scrotum grew Gram-positive cocci, which were initially
      identified as Streptococcus anginosus group by matrix-assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI-TOF MS). However, polymerase
      chain reaction (PCR) amplification and sequencing of the 16S rRNA gene identified
      the isolate as Streptococcus dysgalatiae subspecies equisimilis (SDSE). The
      incidences of invasive S. anginosus group and SDSE infections at the London
      Health Sciences Centre, a tertiary-care institution in southwestern Ontario, were
      determined between August 1, 2011 and August 31, 2012, revealing a slightly lower
      rate of SDSE (3.2 cases per 100,000 population) than other studies. CONCLUSIONS:
      This case highlights a unique disease manifestation of the emerging human
      pathogen Streptococcus dysgalatiae subspecies equisimilis that has not been
      previously reported. This case also underscores the limitations of MALDI-TOF MS
      in differentiating between closely-related streptococcal species which may have
      different pathogenic profiles.

PMID- 23957433
TI  - Tapentadol prolonged release for severe chronic pain: results of a
      noninterventional study involving general practitioners and internists.
AB  - This noninterventional, prospective study investigated the administration of
      tapentadol prolonged release (PR; the dosage form described in this article is
      commercially available in Germany as Palexia retard; Grunenthal GmbH, Aachen) for
      severe chronic pain in routine clinical practice over a 3-month period.
      Effectiveness analyses included data from 3134 patients; 1331 received World
      Health Organization (WHO) Step III pretreatment. A total of 97.8% of patients
      received long-term analgesic pretreatment (42.5% with strong opioids). Switching
      to tapentadol PR produced a 3.9-point mean pain reduction (baseline, 7.0 +/- 1.5;
      end of observation, 3.1 +/- 1.8; 11-point numerical rating scale; descriptive P
      value <=.001); 72.1% of patients experienced clinically relevant pain relief
      (>=50%) at the end of observation. Significant decreases in pain-related
      impairment of daily activities and improvements in quality of life (descriptive P
      value <=.001) were observed with tapentadol PR with good tolerability. Tapentadol
      PR was effective for various pain indications in patients previously receiving
      strong opioids (67.2% achieved clinically relevant pain relief). Tapentadol PR
      can be considered an alternative therapy to classical opioids for treatment of
      severe chronic pain.

PMID- 23957432
TI  - Sevoflurane is less sensitive than halothane for in vitro detection of malignant
      hyperthermia susceptibility.
AB  - BACKGROUND: Sevoflurane is a known triggering agent of malignant hyperthermia
      (MH). The present study analyzed different effects of sevoflurane on skeletal
      muscle of MH susceptible and nonsusceptible individuals in vitro and compared the
      results to the standardized test protocol with halothane and caffeine. A
      potential influence of a present ryanodine receptor type 1 (RyR1) mutation was
      investigated. METHODS: Muscle bundles of 24 MH-susceptible patients with or
      without an RyR1 mutation, 35 MH-nonsusceptible and 10 MH-equivocal patients were
      exposed either to sevoflurane 8 vol% bolus or increasing doses of 2, 4, 6, and 8
      vol%. In MH-positive patients, a screening for mutations in the RyR1 gene was
      performed. RESULTS: The in vitro parameters initial length, weight, predrug
      resting tension, and predrug twitch height did not differ between the groups.
      Sevoflurane caused significant contractures in MH-susceptible but not in MH
      nonsusceptible muscle after increasing doses [1.4 (0.3-6.0) vs. 0 (0-0) mN] and
      after bolus application [6.9 (2.4-21.4) vs. 0 (0-0) mN]. However, only 50% of the
      susceptible patients developed contractures >= 2 mN after increasing
      concentrations while 83% did so after rapid bolus administration. Presence of an
      RyR1 mutation was detected in 36% of the examined MH-positive patients but had no
      influence on developing contractures. CONCLUSION: Sevoflurane-induced
      contractures do not reliably detect MH susceptibility on an individual level.
      Therefore, sevoflurane is no suitable alternative for diagnostic use. Mutation
      specific effects regarding contracture sizes after incubation with sevoflurane,
      halothane, or caffeine were not found.

PMID- 23957435
TI  - My migraine-self-portrait.

PMID- 23957436
TI  - Human papillomavirus infections among Hungarian female sex workers.
AB  - The purpose of this study was to assess the human papillomavirus (HPV) prevalence
      in cervical, oropharyngeal and anal samples of the high-risk population of
      Hungarian female sex workers (FSWs). HPV testing of swab specimens from FSWs (n =
      34) using polymerase chain reaction (PCR) methodology was performed. Results were
      compared with control group (n = 52) matched for age. Questionnaires were used to
      obtain data regarding participants' sexual behaviour. Data were analysed using
      SPSS. HPV DNA was detected in at least one location in a great majority of FSWs
      (82.4%), compared with 46.2% of the general female population (P < 0.05). Both
      the cervical and the anal samples of sex workers showed higher infection rates
      than those of controls (64.7% vs. 34.6% and 50.0% vs. 15.4%, respectively, P <
      0.05). High-risk HPV prevalence was also significantly higher in sex workers
      (55.9% vs. 25.0%, P < 0.05). A significantly higher proportion of FSWs had a
      history of genital warts (26.5% vs. 3.8%, P < 0.05). The results suggest that
      condom use may not result in adequate protection from HPV infection. The high
      infection rates among FSWs should be viewed as a priority group for HPV and
      cervical cancer prevention programmes since they are sources of HPV infection for
      the general population. 

PMID- 23957437
TI  - Systematic review: relationships between sleep and gastro-oesophageal reflux.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GERD) adversely impacts on sleep,
      but the mechanism remains unclear. AIM: To review the literature concerning
      gastro-oesophageal reflux during the sleep period, with particular reference to
      the sleep/awake state at reflux onset. METHODS: Studies identified by systematic
      literature searches were assessed. RESULTS: Overall patterns of reflux during the
      sleep period show consistently that oesophageal acid clearance is slower, and
      reflux frequency and oesophageal acid exposure are higher in patients with GERD
      than in healthy individuals. Of the 17 mechanistic studies identified by the
      searches, 15 reported that a minority of reflux episodes occurred during stable
      sleep, but the prevailing sleep state at the onset of reflux in these studies
      remains unclear owing to insufficient temporal resolution of recording or
      analysis methods. Two studies, in healthy individuals and patients with GERD,
      analysed sleep and pH with adequate resolution for temporal alignment of sleep
      state and the onset of reflux: all 232 sleep period reflux episodes evaluated
      occurred during arousals from sleep lasting less than 15 s or during longer
      duration awakenings. Six mechanistic studies found that transient lower
      oesophageal sphincter relaxations were the most common mechanism of sleep period
      reflux. CONCLUSIONS: Contrary to the prevailing view, subjective impairment of
      sleep in GERD is unlikely to be due to the occurrence of reflux during stable
      sleep, but could result from slow clearance of acid reflux that occurs during
      arousals or awakenings from sleep. Definitive studies are needed on the
      sleep/awake state at reflux onset across the full GERD spectrum.

PMID- 23957438
TI  - Murgocil is a highly bioactive staphylococcal-specific inhibitor of the
      peptidoglycan glycosyltransferase enzyme MurG.
AB  - Modern medicine is founded on the discovery of penicillin and subsequent small
      molecules that inhibit bacterial peptidoglycan (PG) and cell wall synthesis.
      However, the discovery of new chemically and mechanistically distinct classes of
      PG inhibitors has become exceedingly rare, prompting speculation that
      intracellular enzymes involved in PG precursor synthesis are not 'druggable'
      targets. Here, we describe a beta-lactam potentiation screen to identify small
      molecules that augment the activity of beta-lactams against methicillin-resistant
      Staphylococcus aureus (MRSA) and mechanistically characterize a compound
      resulting from this screen, which we have named murgocil. We provide extensive
      genetic, biochemical, and structural modeling data demonstrating both in vitro
      and in whole cells that murgocil specifically inhibits the intracellular membrane
      associated glycosyltransferase, MurG, which synthesizes the lipid II PG substrate
      that penicillin binding proteins (PBPs) polymerize and cross-link into the cell
      wall. Further, we demonstrate that the chemical synergy and cidality achieved
      between murgocil and the beta-lactam imipenem is mediated through MurG dependent
      localization of PBP2 to the division septum. Collectively, these data validate
      our approach to rationally identify new target-specific bioactive beta-lactam
      potentiation agents and demonstrate that murgocil now serves as a highly
      selective and potent chemical probe to assist our understanding of PG
      biosynthesis and cell wall biogenesis across Staphylococcal species. 

PMID- 23957439
TI  - The chemical basis of serine palmitoyltransferase inhibition by myriocin.
AB  - Sphingolipids (SLs) are essential components of cellular membranes formed from
      the condensation of L-serine and a long-chain acyl thioester. This first step is
      catalyzed by the pyridoxal-5'-phosphate (PLP)-dependent enzyme serine
      palmitoyltransferase (SPT) which is a promising therapeutic target. The fungal
      natural product myriocin is a potent inhibitor of SPT and is widely used to block
      SL biosynthesis despite a lack of a detailed understanding of its molecular
      mechanism. By combining spectroscopy, mass spectrometry, X-ray crystallography,
      and kinetics, we have characterized the molecular details of SPT inhibition by
      myriocin. Myriocin initially forms an external aldimine with PLP at the active
      site, and a structure of the resulting co-complex explains its nanomolar affinity
      for the enzyme. This co-complex then catalytically degrades via an unexpected
      'retro-aldol-like' cleavage mechanism to a C18 aldehyde which in turn acts as a
      suicide inhibitor of SPT by covalent modification of the essential catalytic
      lysine. This surprising dual mechanism of inhibition rationalizes the
      extraordinary potency and longevity of myriocin inhibition.

PMID- 23957440
TI  - Electrogeneration of single nanobubbles at sub-50-nm-radius platinum nanodisk
      electrodes.
AB  - The electrochemical generation of individual H(2) nanobubbles at Pt nanodisk
      electrodes immersed in a 0.5 M H(2)SO(4) solution is reported. A sudden drop in
      current associated with the transport-limited reduction of protons is observed in
      the i-V response at Pt nanodisk electrodes with radii of less than 50 nm. This
      decrease in current (~95% blockage) corresponds to the formation of a single H(2)
      nanobubble attached to the nanoelectrode that blocks proton transport to the
      surface. The current at which nanobubble formation occurs, i(nb)(p), is
      independent of scan rate and H(2)SO(4) concentration (for [H(2)SO(4)] > 0.1 M),
      indicating a critical concentration profile of electrogenerated H(2) required to
      nucleate a nanobubble. Finite element simulation based on Fick's first law,
      combined with the Young-Laplace equation and Henry's law, indicates that the
      concentration of H(2) near the nanoelectrode surface at i(nb)(p) exceeds the
      saturation concentration necessary to generate a nanobubble with a size
      comparable to the electrode size. The rapid dissolution of the nanobubble due to
      the high inner Laplace pressure is precisely balanced by the electrogeneration of
      H(2) at the partially exposed Pt surface, resulting in a dynamically stabilized
      nanobubble. Preliminary measurements of the i-t response during nanobubble
      formation indicate a two-step nucleation and growth mechanism with time scales on
      the order of 100 MUs (or less) and ~1 ms, respectively.

PMID- 23957442
TI  - Influence of recombinant duck follistatin protein on embryonic muscle development
      and gene expressions.
AB  - Follistatin (FST) acts as a positive regulator of muscle development by
      inhibiting the activities and expression of myostatin. The recombinant duck FST
      protein was injected into hatching eggs and was also added to the medium of duck
      myoblast to study its role on duck embryonic muscle development and gene
      expressions. Duck embryo weight increased 3.49% (p > 0.05) in FST treatment group
      as compared with control group, but minor effects were found on leg or breast
      muscle weights of ducklings at 2 days post-hatching (p > 0.05). Relative
      expression of Pax7 was upregulated in both leg and breast muscle tissues (p <
      0.05), while MyoD was only upregulated in leg muscle (p < 0.05), and Myf5 was
      only upregulated in breast muscle (p < 0.05). Relative expression of myostatin
      was downregulated in both muscle tissues researched (p < 0.05). In vitro studies
      also showed some maker genes relevant to protein synthesis and degradation,
      cells' proliferation and differentiation had significant changes in myoblasts
      after treated with FST. These results suggested that in ovo feeding of
      recombinant FST protein to duck hatching eggs had an effect on duck embryo
      development but have less roles on the duck embryonic muscle development.

PMID- 23957441
TI  - Changes in droplet surface tension affect the observed hygroscopicity of
      photochemically aged biomass burning aerosol.
AB  - This study examines the hygroscopic and surface tension properties as a function
      of photochemical aging of the aerosol emissions from biomass burning. Experiments
      were conducted in a chamber setting at the UC-Riverside Center for Environmental
      Research and Technology (CE-CERT) Atmospheric Processes Lab using two biomass
      fuel sources, manzanita and chamise. Cloud condensation nuclei (CCN) measurements
      and off-line filter sample analysis were conducted. The water-soluble organic
      carbon content and surface tension of the extracted filter samples were measured.
      Surface tension information was then examined with Kohler theory analysis to
      calculate the hygroscopicity parameter, kappa. Laboratory measurement of biomass
      burning smoke from two chaparral fuels is shown to depress the surface tension of
      water by 30% or more at organic matter concentrations relevant at droplet
      activation. Accounting for surface tension depression can lower the calculated
      kappa by a factor of 2. This work provides evidence for surface tension
      depression in an important aerosol system and may provide closure for differing
      sub- and supersaturated kappa measurements. 

PMID- 23957443
TI  - Validation of the Cardiac Children's Hospital Early Warning Score: an early
      warning scoring tool to prevent cardiopulmonary arrests in children with heart
      disease.
AB  - OBJECTIVE: Most inpatient pediatric arrests are preventable by early
      recognition/treatment of deterioration. Children with cardiac disease have the
      highest arrest rates; however, early warning scoring systems have not been
      validated in this population. The objective of this study was to validate the
      Cardiac Children's Hospital Early Warning Score (C-CHEWS) tool in inpatient
      pediatric cardiac patients. The associated escalation of care algorithm directs:
      routine care (score 0-2), increased assessment/intervention (3-4), or cardiac
      intensive care unit (CICU) consult/transfer (>=5). DESIGN: Sensitivity and
      specificity were estimated based on retrospective review of patients that
      experienced unplanned CICU transfer/arrest (n = 64) and a comparison sample (n =
      248) of admissions. The previously validated Pediatric Early Warning Score (PEWS)
      tool was used for comparison. Patients' highest C-CHEWS scores were compared with
      calculated PEWS scores. Area under the receiver operating characteristic (AUROC)
      curve was calculated for PEWS and C-CHEWS to measure discrimination. RESULTS: The
      AUROC curve for C-CHEWS was 0.917 compared with PEWS 0.785 (P < .001). The
      algorithm AUROC curve was 0.902 vs. PEWS of 0.782. C-CHEWS algorithm sensitivity
      was 96.9 (score >= 2), 79.7 (>=4), and 67.2 (>=5) vs. PEWS of 81.1(>=2), 37.5
      (>=4), and 23.4 (>=5). C-CHEWS specificity was 58.1 (>=2), 85.5 (>=4), and 93.6
      (>=5) vs. PEWS of 81.1 (>=2), 94.8 (>=4) and 97.6 (>=5). Lead time of elevated C
      CHEWS scores (>=2) was a median of 9.25 hours prior to event vs. PEWS, which was
      2.25 hours and lead time for critical C-CHEWS scores (>=5) was 2 hours vs. 0
      hours for PEWS (P < .001). CONCLUSIONS: C-CHEWS has excellent discrimination to
      identify deterioration in children with cardiac disease and performed
      significantly better than PEWS both as an ordinal variable and when choosing cut
      points to maximize AUROC. C-CHEWS has a higher sensitivity than PEWS at all cut
      points.

PMID- 23957444
TI  - An algorithm that administers adaptive speech-in-noise testing to a specified
      reliability at selectable points on the psychometric function.
AB  - OBJECTIVE: To introduce and verify an algorithm designed to administer adaptive
      speech-in- noise testing to a specified reliability at selectable points on the
      psychometric function. DESIGN: Speech-in-noise performances were measured using
      BKB sentences presented in diffuse babble-noise, using morphemic scoring. Target
      of the algorithm was a test-retest standard deviation of 1.13 dB within the
      presentation of 32 sentences. Normal-hearing participants completed repeated
      measures using manual administration targeting 50% correct, and the automated
      procedure targeting 25%, 50%, and 75% correct. Aided hearing-impaired
      participants completed testing with the automated procedure targeting 25%, 50%,
      and 75% correct, repeating measurements at the 50% point three times. STUDY
      SAMPLE: Twelve normal-hearing and 63 hearing-impaired people who had English as
      first language. RESULTS: Relative to the manual procedure, the algorithm produced
      the same speech reception threshold in noise (p = 0.96) and lower test-retest
      reliability on normal-hearing listeners. Both groups obtained significantly
      different results at the three target points (p < 0.04) with observed reliability
      close to expected. Target accuracy was not reached within 32 sentences for 18% of
      measurements on hearing-impaired participants. CONCLUSIONS: The reliability of
      the algorithm was verified. A second test is recommended if the target
      variability is not reached during the first measurement.

PMID- 23957445
TI  - Axiographic and clinical assessment of temporomandibular joint function in
      patients with partial edentulism.
AB  - The aim of this study was to axiographically analyse the mobility of the condyles
      of the temporomandibular joints in patients with partial edentulism in lateral
      sections and try to specify whether the partial edentulism has an impact on the
      severity of temporomandibular disorders. 60 subjects with partial edentulism
      (different range groups) and 20 subjects in the control group (full dental
      arches) were examined. Every patient underwent a thorough clinical examination,
      including axiography conducted by means of Cadiax Compact II(r) system. The
      results show some correlation between the advancement of temporomandibular joint
      disorder, the range of partial edentulism and the abrasion of the residual teeth.
      In the study, a significant intensification of dysfunction symptoms and
      restricted condylar path was observed in patients with the largest partial
      edentulism and significant level of tooth wear of the residual teeth. A
      significantly higher percentage of asymptomatic subjects or those with minor
      dysfunction was also found among the patients with lowest-range partial
      edentulism in lateral sections.

PMID- 23957446
TI  - Evaluation of anti-infective potential of a tribal folklore Odina wodier Roxb
      against some selected microbes and herpes simplex virus associated with skin
      infection.
AB  - AIM: To evaluate the in vitro antimicrobial activity of aqueous and methanol
      extracts of Odina wodier bark (OWB), a folk medicine, against representative
      bacteria, fungi and herpes simplex virus (HSV) associated with skin infections.
      METHODS AND RESULTS: The OWB extract(s) was found to inhibit the isolates of
      Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Klebsiella
      pneumonia, Escherichia coli at an MIC of 256-5000 MUg ml(-1) and Candida albicans
      at and above 4000 MUg ml(-1) by agar and broth dilution assays. The growth curve
      of Staph. aureus revealed the highest activity within 2-6 h of methanol extract
      (ME) exposure. Interestingly, the MTT and plaque reduction assay showed that the
      extracts can inhibit HSV-1 and HSV-2 at EC50 of 22.4 and 28.8 MUg ml(-1) , with
      Selectivity index of 11.7-15. While the time kinetic and binding assays
      demonstrated that the ME at 50 MUg ml(-1) prevents viral attachment into Vero
      cells. Phytochemical and HPLC analysis of ME revealed the presence of flavonoids,
      phytosterols, saponins and tannins including the pseudotannin chlorogenic acid.
      CONCLUSION: The traditional use of OWB for the management of skin infections has
      scientific basis. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated
      the antimicrobial potential of OWB on selected isolates of bacteria, fungi and
      HSV, associated with skin infections.

PMID- 23957447
TI  - The analgesic effect of oxygen during percutaneous coronary intervention (the
      OXYPAIN Trial).
AB  - INTRODUCTION: Oxygen is considered to have analgesic effects, but the evidence is
      weak. Oxygen may be harmful to the ischemic myocardium. The aim was to
      investigate the analgesic effect of oxygen during percutaneous coronary
      intervention (PCI) and to evaluate cardiac injury. MATERIAL AND METHODS: The
      OXYPAIN was a phase II randomized trial with a double blind design. 305 patients
      were randomized to receive oxygen or atmospheric air during PCI. The patients
      were asked to score chest pain by the Visual-Analog Scale (VAS). The use of
      analgesic agents and troponin-t was measured. RESULTS: There was no significant
      difference in pain between the groups: oxygen: 2.0, [2.0-4.0], air: 2.0, [2.0
      5.0] (median, interquartile range: 25-75%, P = 0.12). The median difference in
      score of VAS was [95% CI]: 0, [0-1.0]. The oxygen group received 0.44 +/- 0.11 mg
      of morphine versus 0.46 +/- 0.13, P = n.s. The peak value of troponin-t post-PCI
      was 38, [11-352] nmol/ml in the oxygen group and 61, [16-241] for patients
      treated with air, P = 0.46. CONCLUSIONS: The use of oxygen during PCI did not
      demonstrate any analgesic effect. There was no difference in myocardial injury
      measured with troponin-t or in the morphine dose. Our results do not support
      routine use of oxygen. (NCT01413841.).

PMID- 23957448
TI  - ECG-gated cardiac MDCT for detection of systolic anterior motion of mitral valve.
AB  - OBJECTIVES: Evaluating ECG-gated cardiac MDCT detection of systolic anterior
      motion of the mitral valve, in comparison to trans-thoracic echocardiography as a
      gold standard. MATERIALS AND METHODS: Study group included 83 consecutive
      patients (57 men; average age 56.1 years) evaluated with both retrospective ECG
      gated cardiac MDCT and trans-thoracic echocardiography within an interval of 30
      days. ECG-gated cardiac MDCT imaging was performed with retrospective ECG- gating
      using 64-slice and 128-slice CT scanners with an inherent temporal resolution
      range of 75-165 ms. MDCT's and trans- thoracic echocardiograms were
      retrospectively and independently evaluated by experienced radiologist and
      cardiologist respectively, for presence of systolic anterior motion of the mitral
      valve. RESULTS: 7 patients (8.4%) were found to have systolic anterior motion by
      trans-thoracic echocardiography, from which 6 were found to have systolic
      anterior motion by ECG-gated cardiac MDCT. Of the 76 patients without systolic
      anterior motion on trans-thoracic echocardiography, all were correctly identified
      using ECG-gated cardiac MDCT. The sensitivity, specificity, positive and negative
      predictive values and accuracy of ECG-gated cardiac MDCT in identifying systolic
      anterior motion of the mitral valve were 85.7% (6/7), 100% (76/76), 100% (6/6),
      98.7% (76/77) and 98.8% (82/83), respectively. CONCLUSION: ECG-gated cardiac MDCT
      is comparable to trans-thoracic echocardiography in detecting systolic anterior
      motion of the mitral valve.

PMID- 23957449
TI  - Altered neuropathic pain behaviour in a rat model of depression is associated
      with changes in inflammatory gene expression in the amygdala.
AB  - The association between chronic pain and depression is widely recognized, the
      comorbidity of which leads to a heavier disease burden, increased disability and
      poor treatment response. This study examined nociceptive responding to mechanical
      and thermal stimuli prior to and following L5-L6 spinal nerve ligation (SNL), a
      model of neuropathic pain, in the olfactory bulbectomized (OB) rat model of
      depression. Associated changes in the expression of genes encoding for markers of
      glial activation and cytokines were subsequently examined in the amygdala, a key
      brain region for the modulation of emotion and pain. The OB rats exhibited
      mechanical and cold allodynia, but not heat hyperalgesia, when compared with sham
      operated counterparts. Spinal nerve ligation induced characteristic mechanical
      and cold allodynia in the ipsilateral hindpaw of both sham and OB rats. The OB
      rats exhibited a reduced latency and number of responses to an innocuous cold
      stimulus following SNL, an effect positively correlated with interleukin (IL)-6
      and IL-10 mRNA expression in the amygdala, respectively. Spinal nerve ligation
      reduced IL-6 and increased IL-10 expression in the amygdala of sham rats. The
      expression of CD11b (cluster of differentiation molecule 11b) and GFAP (glial
      fibrillary acidic protein), indicative of microglial and astrocyte activation,
      and IL-1beta in the amygdala was enhanced in OB animals when compared with sham
      counterparts, an effect not observed following SNL. This study shows that
      neuropathic pain-related responding to an innocuous cold stimulus is altered in
      an animal model of depression, effects accompanied by changes in the expression
      of neuroinflammatory genes in the amygdala. 

PMID- 23957450
TI  - Evolution of a hotspot genus: geographic variation in speciation and extinction
      rates in Banksia (Proteaceae).
AB  - BACKGROUND: Hotspots of angiosperm species richness and endemism in Mediterranean
      climate regions are among the most striking, but least well-understood,
      geographic patterns of biodiversity. Recent studies have emphasized the
      importance of rapid diversification within hotspots, compared to non-hotspot
      regions, as a major contributor to these patterns. We constructed the first near
      complete phylogeny of Banksia (Proteaceae) to test whether diversification rates
      have differed between lineages confined to the southwest Australian hotspot and
      those found throughout southern, eastern and northern Australia. We then tested
      for variation in diversification rates among the bioclimatic zones within the
      southwest hotspot itself. RESULTS: Although Banksia species richness in the
      southwest is ten times that of the rest of the continent, we find little evidence
      for more rapid diversification in the southwest, although this result is
      inconclusive. However, we find firmer support for substantial rate variation
      within the southwest hotspot, with more rapid diversification in the semi-arid
      heaths and shrublands, compared to the high-rainfall forests. Most of the Banksia
      diversity of the southwest appears to be generated in the heaths and shrublands,
      with a high migration rate out of this zone boosting diversity of the adjacent
      forest zone. CONCLUSIONS: The geographic pattern of diversification in Banksia
      appears more complex than can be characterized by a simple hotspot vs. non
      hotspot comparison, but in general, these findings contrast with the view that
      the high diversity of Mediterranean hotspots is underpinned by rapid radiations.
      Steady accumulation of species at unexceptional rates, but over long periods of
      time, may also have contributed substantially to the great botanical richness of
      these regions.

PMID- 23957451
TI  - In vivo NMR studies of regional cerebral energetics in MPTP model of Parkinson's
      disease: recovery of cerebral metabolism with acute levodopa treatment.
AB  - In this study, we have evaluated cerebral atrophy, neurometabolite homeostasis,
      and neural energetics in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) model
      of Parkinson's disease. In addition, the efficacy of acute l-DOPA treatment for
      the reversal of altered metabolic functions was also evaluated. Cerebral atrophy
      and neurochemical profile were monitored in vivo using MRI and (1) H MR
      Spectroscopy. Cerebral energetics was studied by (1) H-[(13) C]-NMR spectroscopy
      in conjunction with infusion of (13) C labeled [1,6(-13) C2 ]glucose or [2-(13)
      C]acetate. MPTP treatment led to reduction in paw grip strength and increased
      level of GABA and myo-inositol in striatum and olfactory bulb. (13) C Labeling of
      glutamate-C4 (1.93 +/- 0.24 vs. 1.48 +/- 0.06 MUmol/g), GABA-C2 (0.24 +/- 0.04
      vs. 0.18 +/- 0.02 MUmol/g) and glutamaine-C4 (0.26 +/- 0.04 vs. 0.20 +/- 0.04
      MUmol/g) from [1,6-(13) C2 ]glucose was found to be decreased with MPTP exposure
      in striatum as well as in other brain regions. However, glutamine-C4 labeling
      from [2-(13) C]acetate was found to be increased in the striatum of the MPTP
      treated mice. Acute l-DOPA treatment failed to normalize the increased
      ventricular size and level of metabolites but recovered the paw grip strength and
      (13) C labeling of amino acids from [1,6-(13) C2 ]glucose and [2-(13) C]acetate
      in MPTP-treated mice. These data indicate that brain energy metabolism is
      impaired in Parkinson's disease and acute l-DOPA therapy could temporarily
      recover the cerebral metabolism. Cerebral atrophy, neurometabolite homeostasis,
      and neural energetics have been evaluated in an MPTP model of Parkinson's disease
      using MRI, in vivo (1) H MRS and (1) H-[(13) C]-NMR spectroscopy, respectively.
      MPTP treatment led to reduced paw grip strength and neuronal function. Acute
      Levodopa treatment was able to recover the diminished motor function and cerebral
      function. CMRGlc, Cerebral metabolic rate of glucose oxidation; MPTP, 1-Methyl-4
      phenyl-1,2,3,6-tetrahydropyridin. 

PMID- 23957452
TI  - A rare, human prostate oncocyte cell originates from the prostatic carcinoma
      (DU145) cell line.
AB  - DU145 human prostate carcinoma cells are typically poorly differentiated and
      contain only scantily distributed organelles. However, among numerous tumor cells
      randomly examined by electron microscopy out of in vitro cultivation, a peculiar,
      rare oncocyte-like cell type has been observed whose nucleus appears to be of
      small dimension and with a cytoplasm almost entirely filled with often distorted
      mitochondria. A few small, dispersed lysosomal bodies, small cisterns of the
      endoplasmic reticulum and a few glycogen patches can be found among highly
      osmiophilic contrasted, cytosolic spaces filled by innumerable
      ribonucleoproteins. The excessive population of mitochondria may have arisen from
      a more populated tumor cell type wherein the altered mitochondria are found to
      appear burgeoning into a spherical-like size progeny crowding the tumor cells.
      Literature cited between 1950 and the present suggests that this rare, oncocytic,
      benign prostatic tumor cell type is likely appear epigenetically, stemming from
      an original secretory cell, which is confirmed by the origin of the cell line
      originally maintained as cell line out of a brain metastatic, adenocarcinoma
      niche.

PMID- 23957453
TI  - Bioactive polyprenylated acylphloroglucinol derivatives from Hypericum cohaerens.
AB  - Nine new polyprenylated acylphloroglucinol derivatives, hypercohins B-J (1-9),
      and nine known analogues were isolated from the aerial parts of Hypericum
      cohaerens. The structures of 1-9 were elucidated based on spectroscopic analysis,
      and the absolute configuration of 1 was confirmed by X-ray crystallographic
      analysis. The inhibitory activities of these isolates on acetylcholinesterase and
      five human tumor cell lines were tested, and hypercohins B-D (1-3) exhibited
      moderate inhibitory activity (IC50 5.8-17.9 MUM) against the tested tumor cell
      lines.

PMID- 23957454
TI  - Carboxylate assistance for catalyzed hydroarylations of methylenecyclopropanes.
AB  - Carboxylate assistance enabled efficient and chemoselective ruthenium(II)
      catalyzed hydroarylations and hydroalkenylations of highly strained
      methylenecyclopropanes via C-H bond activation occurring with ring conservation
      of the cyclopropane moieties. 

PMID- 23957455
TI  - Juvenile idiopathic arthritis-associated uveitis: clinical features and
      complications, risk factors for severe course, and visual outcome.
AB  - Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic
      disease and the most prevalent systemic disorder in children with uveitis. The
      risk of developing uveitis is the greatest among patients with oligoarticular
      onset of disease. Clinical features of JIA-associated uveitis (JIAU) are
      nongranulomatous inflammation, anterior in location, insidious at onset, chronic
      course, and frequently asymptomatic in the absence of ocular structural
      complications. Uveitis in JIA can worsen over time with many sight-threatening
      complications, such as band keratopathy in the visual axis, posterior synechiae,
      cataract, secondary glaucoma, macular edema, hypotony, epiretinal membrane, and
      optic nerve edema. Different studies have pointed out that several factors are
      associated with poor prognosis, including young age at onset, male gender, short
      interval between diagnosis of arthritis and uveitis, severity of uveitis at
      onset, and antinuclear antibody (ANA) positivity. Although JIA associated-uveitis
      is still a serious blinding disease, we are at least able to identify the high
      risk group.

PMID- 23957456
TI  - Targeted destruction of fungal structures of Erysiphe trifoliorum on flat leaf
      surfaces of Marchantia polymorpha.
AB  - In this study, we observed the germination behaviour of airborne conidia from
      powdery mildews that settle on thalloid surfaces. We inoculated thalli (flat,
      sheet-like leaf tissues) and gemmae (small, flat, sheet-like leaf tissues that
      propagate asexually via bud-like structures) of the common liverwort (Marchantia
      polymorpha) with conidia from tomato powdery mildew (Oidium neolycopersici; KTP
      02) and red clover powdery mildew (Erysiphe trifoliorum; KRCP-4N) and examined
      their germination and subsequent appressorium formation under a high-fidelity
      digital microscope. Conidial bodies and germ tubes of the inoculated KRCP-4N
      conidia were destroyed on both the thalli and gemmae. The destruction of these
      fungal structures was observed only for KRCP-4N conidia inoculated onto M.
      polymorpha on both leaf surfaces. No differences in destruction of the KRCP-4N
      fungal structures between thalli and gemmae were observed. At 4 h post
      inoculation, destruction of the germ tube tip was observed when it reached the
      gemmae leaf surface. At 6 h post-inoculation, the conidial bodies and germ tubes
      were destroyed. In contrast, KTP-02 conidia were not destroyed and formed normal,
      well-lobed appressoria on the surface of M. polymorpha gemmae.

PMID- 23957457
TI  - From blickets to synapses: inferring temporal causal networks by observation.
AB  - How do human infants learn the causal dependencies between events? Evidence
      suggests that this remarkable feat can be achieved by observation of only a
      handful of examples. Many computational models have been produced to explain how
      infants perform causal inference without explicit teaching about statistics or
      the scientific method. Here, we propose a spiking neuronal network implementation
      that can be entrained to form a dynamical model of the temporal and causal
      relationships between events that it observes. The network uses spike-time
      dependent plasticity, long-term depression, and heterosynaptic competition rules
      to implement Rescorla-Wagner-like learning. Transmission delays between neurons
      allow the network to learn a forward model of the temporal relationships between
      events. Within this framework, biologically realistic synaptic plasticity rules
      account for well-known behavioral data regarding cognitive causal assumptions
      such as backwards blocking and screening-off. These models can then be run as
      emulators for state inference. Furthermore, this mechanism is capable of copying
      synaptic connectivity patterns between neuronal networks by observing the
      spontaneous spike activity from the neuronal circuit that is to be copied, and it
      thereby provides a powerful method for transmission of circuit functionality
      between brain regions. 

PMID- 23957458
TI  - Timing of operation for poor-grade aneurysmal subarachnoid hemorrhage: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Subarachnoid hemorrhage is a common and dangerous disease with an
      unfavorable prognosis. Patients with poor-grade subarachnoid hemorrhage (Hunt &
      Hess Grades 4-5) are unconscious on admission. Because of the high mortality and
      disability rate associated with poor-grade subarachnoid hemorrhage, it is often
      treated conservatively. Timing of surgery for poor-grade aneurysmal subarachnoid
      hemorrhage is still controversial, therefore this study aims to identify the
      optimal time to operate on patients admitted in poor clinical condition.
      METHODS/DESIGN: Ninety-nine patients meeting the inclusion criteria were randomly
      assigned into three treatment groups. The early surgery group received operation
      within 3 days after onset of subarachnoid hemorrhage (day of SAH = day 1); the
      intermediate surgery group received operation from days 4 to 7, and surgery was
      performed on the late surgery group after day 7. Follow-up was performed 1, 3,
      and 6 months after aneurysm clipping. Primary indicators of outcome included the
      Extended Glasgow Outcome Scale and the Modified Rankin Scale, while secondary
      indicators of outcome were assessed using the Barthel Index and mortality.
      DISCUSSION: This is the first prospective, single-center, observer-blinded,
      randomized controlled trial to elucidate optimal timing for surgery in poor-grade
      subarachnoid hemorrhage patients. The results of this study will be used to
      direct decisions of surgical intervention in poor-grade subarachnoid hemorrhage,
      thus improving clinical outcomes for patients. TRIAL REGISTRATION: Chinese
      Clinical Trial Registry: ChiCTR-TRC-12002917.

PMID- 23957459
TI  - Biphasic microreactor for efficient membrane protein pretreatment with a
      combination of formic acid assisted solubilization, on-column pH adjustment,
      reduction, alkylation, and tryptic digestion.
AB  - Combining good dissolving ability of formic acid (FA) for membrane proteins and
      excellent complementary retention behavior of proteins on strong cation exchange
      (SCX) and strong anion exchange (SAX) materials, a biphasic microreactor was
      established to pretreat membrane proteins at microgram and even nanogram levels.
      With membrane proteins solubilized by FA, all of the proteomics sample processing
      procedures, including protein preconcentration, pH adjustment, reduction, and
      alkylation, as well as tryptic digestion, were integrated into an "SCX-SAX"
      biphasic capillary column. To evaluate the performance of the developed
      microreactor, a mixture of bovine serum albumin, myoglobin, and cytochrome c was
      pretreated. Compared with the results obtained by the traditional in-solution
      process, the peptide recovery (93% vs 83%) and analysis throughput (3.5 vs 14 h)
      were obviously improved. The microreactor was further applied for the
      pretreatment of 14 MUg of membrane proteins extracted from rat cerebellums, and
      416 integral membrane proteins (IMPs) (43% of total protein groups) and 103
      transmembrane peptides were identified by two-dimensional nanoliquid
      chromatography-electrospray ionization tandem mass spectrometry (2D nano-LC-ESI
      MS/MS) in triplicate analysis. With the starting sample preparation amount
      decreased to as low as 50 ng, 64 IMPs and 17 transmembrane peptides were
      identified confidently, while those obtained by the traditional in-solution
      method were 10 and 1, respectively. All these results demonstrated that such an
      "SCX-SAX" based biphasic microreactor could offer a promising tool for the
      pretreatment of trace membrane proteins with high efficiency and throughput. 

PMID- 23957460
TI  - Fixing thresholds along the continuum of depressive states.

PMID- 23957461
TI  - Suicides among military conscripts between 1991-2007 in Finland--a descriptive
      replication study.
AB  - BACKGROUND: Suicide mortality in Finland particularly among young people remains
      high, compared with other European countries. Suicide is one of the leading
      causes of death among military conscripts in Finland. AIMS: In this record-based
      study, we investigated characteristics of all 48 suicides among Finnish
      conscripts during the period 1991-2007. METHODS: We collected and analyzed
      healthcare records during military service and medicolegal investigations
      (medicolegal autopsy) of suicide victims. RESULTS: Of the 48 suicides, 36 (75%)
      were completed during leave days. Shooting, hanging and jumping were the most
      common methods used; a service gun was used in four (14%) of the 29 shooting
      cases. One-third of the victims had been in contact with military healthcare
      during the week preceding their suicide, and two-thirds during the preceding
      month. CONCLUSIONS: When conscripts use healthcare services, suicidal thoughts
      should be actively asked of those conscripts with history of any risk factors for
      suicidal behavior.

PMID- 23957462
TI  - Diagnostic accuracy of faecal immunochemical test for screening individuals with
      a family history of colorectal cancer.
AB  - BACKGROUND: The role of a faecal immunochemical test (FIT) in screening
      individuals with a positive family history of colorectal cancer (CRC) is not
      clear. AIM: To assess the diagnostic accuracy of FIT using colonoscopy findings
      as the gold standard in identifying colorectal neoplasms. METHODS: We analysed
      data from 4539 asymptomatic subjects aged 50-70 years who had both colonoscopy
      and FIT (Hemosure; W.H.P.M., Inc, El Monte, CA, USA) at our bowel cancer
      screening centre between 2008 and 2012. A total of 572 subjects (12.6%) had a
      family history of CRC. Our primary outcome was the sensitivity of FIT in
      detecting advanced neoplasms and cancers in subjects with a family history of
      CRC. A family history of CRC was defined as any first-degree relative with a
      history of CRC. RESULTS: Among 572 subjects with a family history of CRC,
      adenoma, advanced neoplasm and cancer were found at screening colonoscopy in
      29.4%, 6.5% and 0.7% individuals, respectively. The sensitivity of FIT in
      detecting adenoma, advanced neoplasm and cancer was 9.5% [95% confidence interval
      (CI), 5.7-15.3], 35.1% (95% CI, 20.7-52.6) and 25.0% (95% CI, 1.3-78.1),
      respectively. Among FIT-negative subjects who have a family history of CRC,
      adenoma was found in 152 (29.6%), advanced neoplasm in 24 (4.7%) and cancer in 3
      (0.6%) individuals. CONCLUSION: Compared with colonoscopy, FIT is more likely to
      miss advanced neoplasms or cancers in individuals with a family history of CRC.

PMID- 23957463
TI  - Are radiation oncologists aware of health literacy among people with cancer
      treated with radiotherapy?
AB  - Health literacy skills are important for people affected by cancer as they are
      exposed to complex treatment and follow-up care information. This study aimed to
      (1) explore radiation oncologists' understandings and awareness of health
      literacy among patients with a reasonable command of English; (2) gain insight
      into oncologists' views regarding health literacy; and (3) identify techniques
      oncologists employ to communicate to different literacy populations. We conducted
      semi-structured interviews with 26 radiation oncologists. Four key themes were
      identified: (1) identifying a patient's literacy level; (2) perceived impact of
      literacy; (3) challenges and strategies to communicating concepts and supporting
      decision-making; and (4) suggested improvements to the health system.
      Participants described subjectively assessing a person's literacy level by
      monitoring the types of questions asked; analysing the language used; examining
      non-verbal behaviour, and considering a person's socio-economic situation.
      Participants reported the challenges of discussing the subtleties of cancer
      treatments with lower literacy groups such as the benefits and risks of treatment
      options and clinical trials, and tended to provide the basic facts to facilitate
      understanding. Radiation oncologists acknowledged the importance of health
      literacy in oncology, and employed a number of techniques to tailor their
      communication to different literacy populations. Further research is needed to
      address the challenges faced by oncologists when interacting with different
      literacy groups. 

PMID- 23957464
TI  - Controlling the ambiphilic nature of sigma-arylpalladium intermediates in
      intramolecular cyclization reactions.
AB  - The reactivity of main group organometallics, such as organolithium compounds
      (RLi) and Grignard reagents (RMgX), is quite straightforward. In these species
      the R group usually exhibits nucleophilic reactivity without any possibility of
      inducing electrophilic character. In contrast, in organopalladium complexes,
      researchers can switch the reactivity from electrophilic to nucleophilic
      relatively simply. Although sigma-aryl and sigma-vinylpalladium complexes are
      commonly used as electrophiles in C-C bond-forming reactions, recent research has
      demonstrated that they can also react with carbon-heteroatom multiple bonds in a
      nucleophilic manner. Nevertheless, researchers have completely ignored the issue
      of controlling the ambiphilic nature of such species. This Account describes our
      efforts toward selectively promoting the same starting materials toward either
      electrophilic alpha-arylation or nucleophilic addition reactions to different
      carbonyl groups. We could tune the properties of the sigma-arylpalladium
      intermediates derived from amino-tethered aryl halides and carbonyl compounds to
      achieve chemoselective transformations. Therefore, chemists can control the
      ambiphilic nature of such intermediates and, consequently, the competition
      between the alternative reaction pathways by the adequate selection of the
      reaction conditions and additives (base, presence/absence of phenol, bidentate
      phosphines). The nature of the carbonyl group (aldehydes, ketones, esters, and
      amides) and the length of the tether connecting it to the aniline moiety also
      play an important role in the outcome of these processes. Our joint computational
      and experimental efforts to elucidate the reaction mechanism of these palladium
      catalyzed transformations suggest that beyond the formation of the four-membered
      azapalladacycle, two major factors help to control the dual character of the
      palladium(II) intermediates derived from 2-haloanilines. First, their high
      nucleophilicity strongly modifies the interaction of the metal center with the
      carbonyl group. Second, the additive phenol exchanges the iodide ligand to give
      an arylpalladium(II) phenoxide complex, which has a beneficial effect on the
      arylation. The formation of this transient intermediate not only stabilizes the
      arylpalladium moiety, thus preventing the nucleophilic attack at the carbonyl
      group, but also assists the enolization reaction, which takes place in a more
      favorable intramolecular manner. The azapalladacycle intermediate is, in the
      words of J. R. R. Tolkien, "the one ring to bring them all and in the darkness to
      bind them." With this intermediate, we can easily achieve the synthesis of a
      variety of heterocyclic systems by selectively promoting electrophilic alpha
      arylation or nucleophilic addition reactions from the same precursors. 

PMID- 23957468
TI  - Synthesis of tetrachalcogenide-substituted phenalenyl derivatives: preparation
      and solid-state characterization of bis(3,4,6,7-tetrathioalkyl-phenalenyl)boron
      radicals.
AB  - We report the synthesis and properties of a series of spiro-bis(3,4,6,7
      tetrachalcogenide-substituted-phenalenyl)boron salts and two of the corresponding
      tetrathioalkyl-substituted spiro-bis(phenalenyl)boron radicals [tetrathiomethyl
      (10) and tetrathioethyl (11)] in which all of the active positions of the
      phenalenyl (PLY) nucleus are functionalized. In the solid state, radicals 10 and
      11 exist as a weak pi-dimers due to the steric congestion of the thioalkyl groups
      in the superimposed PLY units. As a result, the spins are localized in the
      isolated (nonsuperimposed) PLY rings, and the structure, magnetic susceptibility
      measurements, and band structure calculations confirm that these PLY units are
      unable to undergo strong intermolecular interaction as a result of the
      orientation of the thioalkyl groups. 

PMID- 23957469
TI  - Shape-controlled synthesis of hollow silica colloids.
AB  - In this work, hollow silica colloids with different shapes, such as pseudocubes,
      ellipsoids, capsules, and peanuts, have been synthesized through the following
      process: silica coating on the surface of hematite colloidal particles with
      different shapes (pseudocubes, ellipsoids, capsules, and peanuts) and the
      sequential acid dissolution of the hematite cores. The as-obtained hollow silica
      colloids with different shapes have uniform sizes, shapes, and shells. 

PMID- 23957470
TI  - Properties and inflammatory effects of various size fractions of ambient
      particulate matter from Beijing on A549 and J774A.1 cells.
AB  - Particulate matter (PM) is a major ambient air pollutant causing millions of
      premature deaths each year in China. The toxicity of PM is property and size
      dependent. In this study, ambient PM samples collected in Beijing were divided
      into five size fractions with nominal aerodynamic ranges of <0.40, 0.40-1.1, 1.1
      3.3, 3.3-5.8, and 5.8-10 MUm. Individual size fractions were characterized for a
      number of properties including particle size distribution, specific surface area,
      zeta potential, dithiothreitol (DTT)-based redox ability, and contents of water
      soluble organic carbon (WSOC), polycyclic aromatic hydrocarbons (PAHs), selected
      metals, and endotoxin. Human adenocarcinomic alveolar epithelial cell line A549
      and small mouse monocyte-macrophage cell line J774A.1 were tested for their
      relative viabilities and inflammatory effects (interleukine-8 for A549 and tumor
      necrosis factor-alpha for J774A.1) after exposure to PM of various sizes. It was
      found that PM specific area was positively correlated with WSOC, high molecular
      weight PAHs, DTT-based redox ability, negatively correlated with surface zeta
      potential and lithophile metals. Several trace metals from combustion sources
      were enriched in intermediate size fractions. For both endotoxin concentrations
      of the PM and PM induced inflammatory cytokine expressions by the two cell lines,
      there were general increasing trends as PM size increased with an exception of
      the finest fraction, which induced the highest inflammatory effects. It seems
      that the size dependence of cytokine expression was associated with a number of
      properties including endotoxin content, zeta potential, settling velocity, metal
      content, and DTT-based redox ability. 

PMID- 23957471
TI  - Effects of high non-phytate phosphorus starter diet on subsequent growth
      performance and carcass characteristics of broiler chickens.
AB  - The trial was performed to investigate the effects of different concentrations of
      non-phytate phosphorus (nPP) in the starter and grower (with phytase inclusion)
      periods on carcass characteristics, organ weight and weekly variations of growth
      performance in the grower period. Seven hundred and twenty-day-old male broiler
      chickens were randomly assigned to 12 treatments in a completely randomized
      design. Chickens received two dietary treatments (4.5 g/kg and 6 g/kg nPP) in the
      starter (0-21 days) and six experimental diets (4 g/kg, 3.1 g/kg, 2.3 g/kg and
      2.3 g/kg + 1000 FTU/Kg of feed phytase, 1.5 g/kg, 1.5 g/kg nPP + 1000 FTU/Kg of
      feed phytase) in the grower period (22-42 days). Results showed that phytase
      inclusion in the second and third weeks of grower period could increase feed
      intake significantly. Also, decrease in the concentrations of nPP to 1.5 g/kg
      caused to decline body weight gain markedly. Moreover, there is a significant
      difference between 4.5 g/kg and 6 + 4 g/kg nPP (starter+grower) and 1.5 g/kg nPP.
      Phytase inclusion increased carcass yield and declined liver weight
      significantly. Dietary treatment of 4.5 + 1.5 g/kg nPP enhanced heart and liver
      weight markedly. It is concluded that starter diets with increased concentration
      of nPP (6 g/kg nPP) had no beneficial effects on growth performance in the
      starter and grower period in the total (0-42 days). Also, it is possible to
      decrease nPP concentration of grower diets to 1.5 and 2.3 g/kg with and without
      phytase inclusion respectively. 

PMID- 23957472
TI  - Atmospheric pressure, nonthermal plasma inactivation of MS2 bacteriophage: effect
      of oxygen concentration on virucidal activity.
AB  - AIMS: The main aim of this study was to determine the virucidal inactivation
      efficacy of an in-house-designed atmospheric pressure, nonthermal plasma jet
      operated at varying helium/oxygen feed gas concentrations against MS2
      bacteriophage, widely employed as a convenient surrogate for human norovirus.
      METHODS AND RESULTS: The effect of variation of percentage oxygen concentration
      in the helium (He) carrier gas was studied and found to positively correlate with
      MS2 inactivation rate, indicating a role for reactive oxygen species (ROS) in
      viral inactivation. The inactivation rate constant increased with increasing
      oxygen concentrations up to 0.75% O2 . 3 log10 (99.9%) reductions in MS2
      viability were achieved after 3 min of exposure to the plasma source operated in
      a helium/oxygen (99.25% : 0.75%) gas mixture, with >7 log10 reduction after 9 min
      exposure. CONCLUSIONS: Atmospheric pressure, nonthermal plasmas may have utility
      in the rapid disinfection of virally contaminated surfaces for infection control
      applications. SIGNIFICANCE AND IMPACT OF STUDY: The atmospheric pressure,
      nonthermal plasma jet employed in this study exhibits rapid virucidal activity
      against a norovirus surrogate virus, the MS2 bacteriophage, which is superior to
      previously published inactivation rates for chemical disinfectants.

PMID- 23957473
TI  - Associations between vascular endothelial growth factor gene polymorphisms and
      pre-eclampsia susceptibility: a meta-analysis.
AB  - OBJECTIVE: The aim of this study was to assess whether vascular endothelial
      growth factor (VEGF) polymorphisms are associated with susceptibility to pre
      eclampsia. METHODS: A meta-analysis was conducted on the associations between the
      -634 C/G, +936 C/T, -1154 A/G, and -2578 A/C polymorphisms of VEGF and pre
      eclampsia. RESULTS: Ten studies involving 2068 subjects (pre-eclampsia, 950;
      controls, 1118) were included in the meta-analysis. The meta-analysis revealed an
      association between pre-eclampsia and the VEGF -634 C allele in overall group (OR
      = 1.351, 95% CI = 1.105-1.651, p = 0.003) and in European group (OR = 1.427, 95%
      CI = 1.139-1.787, p = 0.002). The meta-analysis revealed an association between
      pre-eclampsia and the VEGF -936 T allele in Asians, but not in Europeans (OR =
      1.555, 95% CI = 1.232-1.961, p = 1.9 * 10(-5); OR = 1.587, 95% CI = 0.933-2.699,
      p = 0.088). However, the meta-analysis revealed no association between pre
      eclampsia and the VEGF -1154 A/G and 2578 A/C polymorphisms CONCLUSIONS: This
      meta-analysis suggested that the VEGF -634 C/G polymorphism is associated with
      susceptibility to pre-eclampsia in Europeans and that the VEGF -634 C/G
      polymorphism is associated with pre-eclampsia in Asians.

PMID- 23957474
TI  - The analysis of the effect of wrought wire clasps on the conditions of abutment
      teeth.
AB  - Laboratory evaluation of spring constants (k) of wrought wire clasps (WWC)
      separated from removable partial denture (RPD) and the results of tibological
      tests which represent the dependence of enamel wear with normal force have been
      presented in the paper. The results of laboratory examinations have been combined
      with the results of clinical assessment of the level of abutment teeth wear. On
      the basis of the examinations performed it has been revealed that the following
      factors have the greatest impact on tribological wear of abutment teeth: the time
      of using RPD and the normal force exerted by WWC on abutment tooth. Normal force
      depends to a great extent on the place of contact of WWC with the tooth. It has
      also been found that abutment teeth featuring higher scale of wear are more
      loosened. The diameter of wire used for making WWC, total length of the arm and k
      determined for the total length of the arm did not have any impact upon the scale
      of wear of abutment teeth.

PMID- 23957476
TI  - Development and validation of a 96-well cellular assay for the discovery of
      ALDH1A1 inhibitors.
AB  - Retinoic acid, the active metabolite of vitamin A, plays important roles in
      various physiological and pathological processes. The two-step production of
      retinoic acid from vitamin A (retinol) is catalyzed by alcohol dehydrogenases and
      aldehyde dehydrogenases, which are potential therapeutic targets for numerous
      diseases, such as obesity, diabetes, and cancer. Currently, the lack of a
      suitable high-throughput cellular assay hinders efforts to identify therapeutic
      small molecular inhibitors of aldehyde dehydrogenase, such as ALDH1A1. In this
      report, we utilized high-content imaging technology and a commercially available
      cell permeable ALDH substrate to develop a 96-well cellular ALDH1A1 assay. This
      assay has a robust and sensitive readout and is amenable to automation. With this
      cellular assay, we identified potent selective ALDH1A1 inhibitors to explore the
      role of retinoic acid production in various preclinical disease models.

PMID- 23957477
TI  - [Prospects for young academics and clinicians in dermatology].

PMID- 23957479
TI  - Basic diagnostics in andrology.
AB  - Basic andrological diagnosis consists of taking the patient's medical history and
      the couple's history as well as performing a physical examination including
      genital ultrasound, spermiogram, and hormonal analysis. If needed, a testicular
      biopsy and genetic testing may also be performed. Recent studies have shown the
      effect of lifestyle factors on male fertility. Thus, the patient history and
      clinical/andrological examinations have been broadened to include information on
      metabolic disorders like obesity and diabetes mellitus. The biggest changes
      occurred with the publication of the fifth edition of the WHO laboratory manual
      in 2010 and the introduction of a section on semen analysis in the German Medical
      Association guidelines (RiliBAK). The reference values for almost all spermiogram
      parameters were adapted in an evidence-based approach using worldwide prospective
      population studies. For central parameters such as sperm motility and morphology,
      the assessment criteria were changed. New independent markers such as sperm DNA
      fragmentation rate are now routinely used in clinical diagnosis. For German
      andrological laboratories, there are now mandatory quality assurance measures for
      semen analysis (in the German "Rili-BAK" guidelines). These include duplicate
      testing of all standard semen parameters and inter-laboratory comparison at
      regular intervals. 

PMID- 23957481
TI  - New developments in dermatological oncogenetics.
AB  - Activated intracellular signaling pathways based on mutations in oncogenes and
      tumor suppressor genes play an important role in a variety of malignant tumors.
      In dermatology, such mutations have been identified in melanoma, basal cell
      carcinoma and squamous cell carcinoma. These have partly led to the establishment
      of new, targeted therapies. Treatment successes have been particularly impressive
      for melanoma with small molecule inhibitors directed against the mutated BRAF
      oncogene and in basal cell carcinoma with inhibitors directed against the
      hedgehog signaling pathway. New sequencing technologies, in particular next
      generation sequencing, have led to a better and more comprehensive understanding
      of malignant tumors. This approach confirmed the pathogenic role of BRAF, NRAS
      and MAP kinase pathways for melanoma. At the same time, a series of further
      interesting target molecules with oncogenic mutations such as ERBB4, GRIN2A,
      GRM3, PREX2, RAC1 and TP53 were identified. New aspects have recently been shown
      for squamous cell carcinoma by detection of mutations in the NOTCH signaling
      pathway. A better understanding of the pathogenesis of these and other tumors
      should lead to improved and maybe even individualized treatment. The current
      developments in dermatological oncogenetics based on the new sequencing
      technologies are reviewed. 

PMID- 23957483
TI  - Influenza vaccination rate among patients with moderate to severe psoriasis.
AB  - BACKGROUND: Patients with chronic inflammatory diseases such as psoriasis
      vulgaris represent a risk group for developing serious complications after
      influenza virus infection. By vaccinating this cohort such complications might be
      prevented. The objective was to determine the vaccination rate among patients
      with moderate to severe psoriasis and to explore the surrounding circumstances.
      PATIENTS AND METHODS: A nationwide, non-interventional, cross-sectional study was
      performed in 1,229 adults with confirmed psoriasis or psoriatic arthritis. The
      survey consisting of 15 questions about vaccination and vaccination adherence was
      distributed to patients enrolled in the psoriasis patient registry "PsoBest".
      RESULTS: About 28 % of the patients (95 %-CI 24.0-31.6) were vaccinated. The mean
      age was 58 years, 40 % were females. The prevalence of psoriatic arthritis was 28
      % at baseline and 39 % during the vaccination period. General practitioners
      vaccinated 50 % of the patients, while dermatologists suggested vaccination in 7
      % of the cases. Fifty percent of the patients reported that they had been
      vaccinated at their own request. 91 % of the patients had been vaccinated at
      least once over the past ten years, receiving on average 5.9 influenza
      vaccinations during the decade. CONCLUSIONS: The vaccination rate in the study
      cohort was relatively low compared to that in the general population. Influenza
      vaccination had only been suggested by a small percentage of physicians.

PMID- 23957488
TI  - [Letter regarding "Thisk legs - it is not always lipoedema" by von Reich-Schupke
      S, AlmeyerP and Stucker M ].

PMID- 23957489
TI  - [Opinion letter to the editor by Dr. Schuchardt to our article "thick legs - it
      is not always lipoedema"].

PMID- 23957490
TI  - [Self-help groups in dermatology--a survey in Germany].

PMID- 23957494
TI  - [High-ranking publications of Dermato-Oncology].

PMID- 23957498
TI  - Nonyloxytryptamine mimics polysialic acid and modulates neuronal and glial
      functions in cell culture.
AB  - Polysialic acid (PSA) is a major regulator of cell-cell interactions in the
      developing nervous system and in neural plasticity in the adult. As a polyanionic
      molecule with high water-binding capacity, PSA increases the intercellular space
      generating permissive conditions for cell motility. PSA enhances stem cell
      migration and axon path finding and promotes repair in the lesioned peripheral
      and central nervous systems, thus contributing to regeneration. As a next step in
      developing an improved PSA-based approach to treat nervous system injuries, we
      searched for small organic compounds that mimic PSA and identified as a PSA
      mimetic 5-nonyloxytryptamine oxalate, described as a selective 5
      hydroxytryptamine receptor 1B (5-HT1B ) agonist. Similar to PSA, 5
      nonyloxytryptamine binds to the PSA-specific monoclonal antibody 735, enhances
      neurite outgrowth of cultured primary neurons and process formation of Schwann
      cells, protects neurons from oxidative stress, reduces migration of astrocytes
      and enhances myelination in vitro. Furthermore, nonyloxytryptamine treatment
      enhances expression of the neural cell adhesion molecule (NCAM) and its
      polysialylated form PSA-NCAM and reduces expression of the microtubule-associated
      protein MAP2 in cultured neuroblastoma cells. These results demonstrate that 5
      nonyloxytryptamine mimics PSA and triggers PSA-mediated functions, thus
      contributing to the repertoire of molecules with the potential to improve
      recovery in acute and chronic injuries of the mammalian peripheral and central
      nervous systems. Polysialic acid (PSA) plays important roles in nervous system
      development, as well as synaptic plasticity and regeneration in the adult. 5
      Nonyloxytryptamine oxalate (5-NOT) mimics PSA and triggers PSA-mediated functions
      in neurons and glial cells. 5-NOT stimulates neuritogenesis, myelination and
      Schwann cell migration. This study sets the basis to develop a PSA-mediated
      therapy of acute and chronic nervous system diseases. 

PMID- 23957497
TI  - Life cycle evolution: was the eumetazoan ancestor a holopelagic, planktotrophic
      gastraea?
AB  - BACKGROUND: Two theories for the origin of animal life cycles with planktotrophic
      larvae are now discussed seriously: The terminal addition theory proposes a
      holopelagic, planktotrophic gastraea as the ancestor of the eumetazoans with
      addition of benthic adult stages and retention of the planktotrophic stages as
      larvae, i.e. the ancestral life cycles were indirect. The intercalation theory
      now proposes a benthic, deposit-feeding gastraea as the bilaterian ancestor with
      a direct development, and with planktotrophic larvae evolving independently in
      numerous lineages through specializations of juveniles. RESULTS: Information from
      the fossil record, from mapping of developmental types onto known phylogenies,
      from occurrence of apical organs, and from genetics gives no direct information
      about the ancestral eumetazoan life cycle; however, there are plenty of examples
      of evolution from an indirect development to direct development, and no
      unequivocal example of evolution in the opposite direction. Analyses of scenarios
      for the two types of evolution are highly informative. The evolution of the
      indirect spiralian life cycle with a trochophora larva from a planktotrophic
      gastraea is explained by the trochophora theory as a continuous series of
      ancestors, where each evolutionary step had an adaptational advantage. The loss
      of ciliated larvae in the ecdysozoans is associated with the loss of outer
      ciliated epithelia. A scenario for the intercalation theory shows the origin of
      the planktotrophic larvae of the spiralians through a series of specializations
      of the general ciliation of the juvenile. The early steps associated with the
      enhancement of swimming seem probable, but the following steps which should lead
      to the complicated downstream-collecting ciliary system are without any
      advantage, or even seem disadvantageous, until the whole structure is functional.
      None of the theories account for the origin of the ancestral deuterostome
      (ambulacrarian) life cycle. CONCLUSIONS: All the available information is
      strongly in favor of multiple evolution of non-planktotrophic development, and
      only the terminal addition theory is in accordance with the Darwinian theory by
      explaining the evolution through continuous series of adaptational changes. This
      implies that the ancestor of the eumetazoans was a holopelagic, planktotrophic
      gastraea, and that the adult stages of cnidarians (sessile) and bilaterians
      (creeping) were later additions to the life cycle. It further implies that the
      various larval types are of considerable phylogenetic value.

PMID- 23957499
TI  - Cupration of C2F5H: isolation, structure, and synthetic applications of
      [K(DMF)2][(t-BuO)Cu(C2F5)]. Highly efficient pentafluoroethylation of unactivated
      aryl bromides.
AB  - Pentafluoroethane, C2F5H (HFC-125), is smoothly cuprated with preisolated or in
      situ-generated [K(DMF)][(t-BuO)2Cu] to give [K(DMF)2][(t-BuO)Cu(C2F5)] (1) in
      nearly quantitative yield. Complex 1 has been isolated, structurally
      characterized, and demonstrated to be an exceedingly versatile
      pentafluoroethylating reagent for a variety of substrates, including unactivated
      aryl bromides. 

PMID- 23957501
TI  - Enantioselective synthesis of cis-3-fluoropiperidin-4-ol, a building block for
      medicinal chemistry.
AB  - The first enantioselective route to both enantiomers of cis-1-Boc-3
      fluoropiperidin-4-ol, a highly prized building block for medicinal chemistry, is
      reported. An enantioselective fluorination is employed, taking advantage of the
      methodology reported by MacMillan, which uses a modified cinchona alkaloid
      catalyst. In studying the fluorination reaction, we have shown that the catalyst
      can be replaced by commercially available primary amines, including alpha
      methylbenzylamine, with similar levels of enantioselectivity. The piperidinols
      are readily crystallized to obtain enantiopure material. 

PMID- 23957500
TI  - A new tool improves diagnostic test performance for transmission em evaluation of
      axonemal dynein arms.
AB  - Abstract Diagnosis of primary ciliary dyskinesia (PCD) by identification of
      dynein arm loss in transmission electron microscopy (TEM) images can be
      confounded by high background noise due to random electron-dense material within
      the ciliary matrix, leading to diagnostic uncertainty even for experienced
      morphologists. The authors developed a novel image analysis tool to average the
      axonemal peripheral microtubular doublets, thereby increasing microtubular signal
      and reducing random background noise. In a randomized, double-blinded study that
      compared two experienced morphologists and three different diagnostic approaches,
      they found that use of this tool led to improvement in diagnostic TEM test
      performance. 

PMID- 23957502
TI  - Reaction of arynes with vinylogous amides: nucleophilic addition to the ortho
      quinodimethide intermediate.
AB  - The reaction of arynes with vinylogous amides containing no free N-H bonds
      proceeds in a [2 + 2] cycloaddition fashion at ambient temperature. The
      electronic properties of the vinylogous amides allow for the cycloadducts
      undergoing a facile ring-opening process, leading to electronically biased ortho
      quinodimethide intermediates. Subsequent nucleophilic addition with alcohols
      affords 2-substituted benzaldehydes or ketones. 

PMID- 23957504
TI  - All giraffes have female-specific properties: influence of grammatical gender on
      deductive reasoning about sex-specific properties in German speakers.
AB  - Grammatical gender is independent of biological sex for the majority of animal
      names (e.g., any giraffe, be it male or female, is grammatically treated as
      feminine). However, there is apparent semantic motivation for grammatical gender
      classes, especially in mapping human terms to gender. This research investigated
      whether this motivation affects deductive inference in native German speakers. We
      compared German with Japanese speakers (a language without grammatical gender)
      when making inferences about sex-specific biological properties. We found that
      German speakers tended to erroneously draw inferences when the sex in the premise
      and grammatical gender of the target animal agreed. An over-generalization of the
      grammar-semantics mapping was found even when the sex of the target was
      explicitly indicated. However, these effects occurred only when gender-marking
      articles accompanied the nouns. These results suggest that German speakers
      project sex-specific biological properties onto gender-marking articles but not
      onto conceptual representations of animals per se. 

PMID- 23957503
TI  - Elevated serum levels of interleukin-17A in uveitis patients.
AB  - PURPOSE: T helper 17 cells (Th17) are one of the main pathogenic effectors in
      autoimmune uveitis, and IL-17A is the signature cytokine of Th17 cells. This
      study aims to assess serum IL-17A levels in patients with autoimmune uveitis and
      evaluate associations between IL-17A levels and disease characteristics. METHODS:
      Serum IL-17A levels from 87 autoimmune uveitis patients and 60 healthy controls
      were assessed using an enzyme-linked immunosorbent assay. Among this cohort, 9
      patients were followed longitudinally for IL-17A levels during active and
      inactive stages of their disease. RESULTS: Median serum IL-17A levels were higher
      among uveitis patients compared to controls (p < 0.0001). Moreover, IL-17A levels
      were elevated among uveitis patients with active disease compared to those with
      inactive disease (p = 0.0202). Among the 9 patients followed longitudinally, IL
      17A levels were elevated during active disease compared to the inactive stage (p
      = 0.0078). CONCLUSIONS: Serum IL-17A levels are elevated in uveitis patients,
      particularly in active uveitis.

PMID- 23957505
TI  - Root antioxidant responses of two Pisum sativum cultivars to direct and induced
      Fe deficiency.
AB  - The contribution of antioxidant defence systems in different tolerance to direct
      and bicarbonate-induced Fe deficiency was evaluated in two pea cultivars
      (Kelvedon, tolerant and Lincoln, susceptible). Fe deficiency enhanced lipid
      peroxidation and H2 O2 concentration in roots of both cultivars, particularly in
      the sensitive one grown under bicarbonate supply. The results obtained on
      antioxidant activities (SOD, CAT, POD) suggest that H2 O2 accumulation could be
      due to an overproduction of this ROS and, at the same time, to a poor capacity to
      detoxify it. Moreover, under bicarbonate supply the activity of POD isoforms was
      reduced only in the sensitive cultivar, while in the tolerant one a new isoform
      was detected, suggesting that POD activity might be an important contributor to
      pea tolerance to Fe deficiency. The presence of bicarbonate also resulted in
      stimulation of GR, MDHAR and DHAR activities, part of the ASC-GSH pathway, which
      was higher in the tolerant cultivar than in the sensitive one. Overall, while in
      the absence of Fe only slight differences were reported between the two
      cultivars, the adaptation of Kelvedon to the presence of bicarbonate seems to be
      related to its greater ability to enhance the antioxidant response at the root
      level.

PMID- 23957506
TI  - Plasma S-adenosylmethionine, DNMT polymorphisms, and peripheral blood LINE-1
      methylation among healthy Chinese adults in Singapore.
AB  - BACKGROUND: Global hypomethylation of repetitive DNA sequences is believed to
      occur early in tumorigenesis. There is a great interest in identifying factors
      that contribute to global DNA hypomethylation and associated cancer risk. We
      tested the hypothesis that plasma S-adenosylmethionine (SAM) level alone or in
      combination with genetic variation in DNA methyltransferases (DNMT1, DNMT3A and
      DNMT3B) was associated with global DNA methylation extent at long interspersed
      nucleotide element-1 (LINE-1) sequences. METHODS: Plasma SAM level and LINE-1 DNA
      methylation index were measured using stored blood samples collected from 440
      healthy Singaporean Chinese adults during 1994-1999. Genetic polymorphisms of 13
      loci in DNMT1, DNMT3A and DNMT3B were determined. RESULTS: LINE-1 methylation
      index was significantly higher in men than in women (p = 0.001). LINE-1
      methylation index was positively associated with plasma SAM levels (p <= 0.01),
      with a plateau at approximately 78% of LINE-1 methylation index (55 nmol/L plasma
      SAM) in men and 77% methylation index (50 nmol/L plasma SAM) in women. In men
      only, the T allele of DNMT1 rs21124724 was associated with a statistically
      significantly higher LINE-1 methylation index (ptrend = 0.001). The DNMT1
      rs2114724 genotype modified the association between plasma SAM and LINE-1
      methylation index at low levels of plasma SAM in men. CONCLUSIONS: Circulating
      SAM level was associated with LINE-1 methylation status among healthy Chinese
      adults. The DNMT1 genetic polymorphism may exert a modifying effect on the
      association between SAM and LINE-1 methylation status in men, especially when
      plasma SAM level is low. Our findings support a link between plasma SAM and
      global DNA methylation status at LINE-1 sequences.

PMID- 23957507
TI  - Association between baseline serum vascular endothelial growth factor levels and
      response to electroconvulsive therapy.
AB  - OBJECTIVE: Several studies have shown that vascular endothelial growth factor
      (VEGF) is implicated in different neuronal processes involved in major depressive
      disorder (MDD) and in the mechanisms of action of antidepressants. The aim of
      this study was to investigate whether VEGF serum levels before treatment might be
      associated with the antidepressant response. METHOD: Two groups of patients were
      enrolled. One was composed of 50 MDD patients receiving an antidepressant drug
      treatment. Illness severity was measured before the treatment (T0) and after 12
      weeks (T1). The second group was composed of 67 treatment-resistant depressed
      (TRD) patients undergoing electroconvulsive therapy (ECT). Illness severity was
      assessed before the treatment (T0) and 1 month after the end of ECT (T1). Blood
      samples for VEGF measurements were collected for both groups at the baseline
      (T0). RESULTS: A significant correlation was observed between baseline VEGF serum
      levels and the percentage reduction in depressive symptomatology after ECT (P =
      0.003). In particular, VEGF levels at baseline were significantly lower in
      patients showing no response to ECT at follow-up (P = 0.008). No correlation
      between T0 VEGF concentrations and drug treatment outcome was found. CONCLUSION:
      Our results suggest that VEGF plays a role in the mechanism of response to ECT.

PMID- 23957508
TI  - Research outcomes and recommendations for the assessment of progression in cancer
      clinical trials.

PMID- 23957509
TI  - Missing data and censoring in the analysis of progression-free survival in
      oncology clinical trials.
AB  - Progression-free survival (PFS) is increasingly used as a primary endpoint in
      oncology clinical trials. However, trial conduct is often such that PFS data on
      some patients may be partially missing either due to incomplete follow-up for
      progression, or due to data that may be collected but confounded by patients
      stopping randomized therapy or starting alternative therapy prior to progression.
      Regulatory guidance on how to handle these patients in the analysis and whether
      to censor these patients differs between agencies. We present results of a
      reanalysis of 28 Phase III trials from 12 companies or institutions performed by
      the Pharmaceutical Research and Manufacturers Association-sponsored PFS Expert
      Team. We show that analyses not adhering to the intention-to-treat principle tend
      to give hazard ratio estimates further from unity and describe several factors
      associated with this shift. We present illustrative simulations to support these
      findings and provide recommendations for the analysis of PFS.

PMID- 23957510
TI  - Evaluation of discordance measures in oncology studies with blinded independent
      central review of progression-free survival using an observational error model.
AB  - To confirm results obtained from local evaluation at investigational centers,
      many oncology studies utilize blinded independent central review (BICR) to make
      assessments of the primary endpoint, progression-free survival (PFS). The
      comparison of data often leads to large discordances between these observations,
      casting doubt on the reliability of the estimated treatment effects from these
      trials. Here we propose new statistics to measure discordance and evaluate their
      utility to detect bias in the local evaluation of progression relative to the
      standard measures of discordance. A new observational error model is proposed
      that can be used to describe the discordance in patient assessments between
      multiple readers.

PMID- 23957511
TI  - A review of statistical issues with progression-free survival as an interval
      censored time-to-event endpoint.
AB  - Frequent rise of interval-censored time-to-event data in randomized clinical
      trials (e.g., progression-free survival [PFS] in oncology) challenges statistical
      researchers in the pharmaceutical industry in various ways. These challenges
      exist in both trial design and data analysis. Conventional statistical methods
      treating intervals as fixed points, which are generally practiced by
      pharmaceutical industry, sometimes yield inferior or even flawed analysis results
      in extreme cases for interval-censored data. In this article, we examine the
      limitation of these standard methods under typical clinical trial settings and
      further review and compare several existing nonparametric likelihood-based
      methods for interval-censored data, methods that are more sophisticated but
      robust. Trial design issues involved with interval-censored data comprise another
      topic to be explored in this article. Unlike right-censored survival data,
      expected sample size or power for a trial with interval-censored data relies
      heavily on the parametric distribution of the baseline survival function as well
      as the frequency of assessments. There can be substantial power loss in trials
      with interval-censored data if the assessments are very infrequent. Such an
      additional dependency controverts many fundamental assumptions and principles in
      conventional survival trial designs, especially the group sequential design
      (e.g., the concept of information fraction). In this article, we discuss these
      fundamental changes and available tools to work around their impacts. Although
      progression-free survival is often used as a discussion point in the article, the
      general conclusions are equally applicable to other interval-censored time-to
      event endpoints.

PMID- 23957512
TI  - Estimating the effect of multiple imputation on incomplete longitudinal data with
      application to a randomized clinical study.
AB  - For analyzing incomplete longitudinal data, there has been recent interest in
      comparing estimates with and without the use of multiple imputation along with
      mixed effects model and generalized estimating equations. Empirically, the
      additional use of multiple imputation generally led to overestimated variances
      and may yield more heavily biased estimates than the use of last observation
      carried forward. Under ignorable or nonignorable missing values, a mixed effects
      model or generalized estimating equations alone yielded more unbiased estimates.
      The different methods were also assessed in a randomized controlled clinical
      trial.

PMID- 23957513
TI  - Bayesian inference for skew-normal mixture models with left-censoring.
AB  - Assays to measure concentration of antibody after vaccination are often subject
      to left-censoring due to a lower detection limit (LDL), leading to a high
      proportion of observations below the detection limit. Not accounting for such
      left-censoring appropriately can lead to biased parameter estimates. To properly
      adjust for left-censoring and a high proportion of observations at LDL, this
      article proposes a mixture model combining a point mass below LDL and a Tobit
      model with skew-elliptical error distribution. We show that skew-elliptical
      distributions, where the skew-normal and skew-t are special cases, have great
      flexibility for simultaneously handling left-censoring, skewness, and heaviness
      in the tails of a distribution of a response variable with left-censored data. A
      Bayesian procedure is used to estimate model parameters. Two real data sets from
      a study of the measles vaccine and an HIV/AIDS study are used to illustrate the
      proposed models.

PMID- 23957514
TI  - A note on partial covariate-adjustment and design considerations in
      noninferiority trials when patient-level data are not available.
AB  - The traditional fixed margin approach to evaluating an experimental treatment
      through an active-controlled noninferiority trial is simple and straightforward.
      However, its utility relies heavily on the constancy assumption of the
      experimental data. The recently developed covariate-adjustment method permits
      more flexibility and improved discriminatory capacity compared to the fixed
      margin approach. However, one major limitation of this covariate-adjustment
      methodology is its adherence on the patient-level data, which may not be
      accessible to investigators in practice. In this article, under some assumptions,
      we examine the feasibility of a partial covariate-adjustment approach based on
      data typically available from journal publications or other public data when the
      patient-level data are unavailable. We illustrate the usefulness of this approach
      through two real examples. We also provide design considerations on the
      efficiency of the partial covariate-adjustment approach.

PMID- 23957515
TI  - A consistency approach for evaluation of biosimilar products.
AB  - Recently, biosimilars have attracted much attention from sponsors and regulatory
      authorities, while patents on early biological products will soon expire in the
      next few years. The European Medicines Agency (EMEA) of the European Union (EU)
      published a guideline on similar biological medicinal products for approval of
      these products in 2005 . Based on the foundational principles of the EMEA
      guideline, biosimilars are expected to be similar, not identical, to the
      innovator biologics they seek to copy. In this article, we develop a consistency
      approach for assessment of similarity between a biosimilar product and the
      innovator biologic. A method for sample size determination for conducting a
      clinical trial to assess the biosimilar product is also proposed. A numerical
      example is given to illustrate applications of the proposed approach in different
      scenarios.

PMID- 23957516
TI  - Optimal timing for interim analyses in clinical trials.
AB  - In clinical trials, interim analyses are often performed before the completion of
      the trial. The intention is to possibly terminate the trial early or adjust the
      sample size. The time of conducting an interim analysis affects the probability
      of the early termination and the number of subjects enrolled until the interim
      analysis. This influences the expected total number of subjects. In this study,
      we examine the optimal time for conducting interim analyses with a view to
      minimizing the expected total sample size. It is found that regardless of the
      effect size, the optimal time of one interim analysis for the early termination
      is approximately two-thirds of the planned observations for the O'Brien-Fleming
      type of spending function and approximately half of the planned observations for
      the Pocock type when the subject enrollment is halted for the interim analysis.
      When the subject enrollment is continuous throughout the trial, the optimal time
      for the interim analysis varies according to the follow-up duration. We also
      consider the time for one interim analysis including the sample size adjustment
      in terms of minimizing the expected total sample size.

PMID- 23957517
TI  - Randomized two-stage Phase II clinical trial designs based on Barnard's exact
      test.
AB  - In areas such as oncology, two-stage designs are often preferred as compared to
      one-stage designs due to the ability to stop the trial early when faced with
      evidence of lack of sufficient efficacy and the associated sample size savings.
      We present exact two-stage designs based on Barnard's exact test for differences
      in proportions and compare the designs to those proposed by Kepner ( 2010 ) and
      Jung ( 2010 ). In addition, we present tables of decision rules under a variety
      of assumed realities for use in trial planning. The procedure is recommended for
      use due to the substantial sample size savings experienced.

PMID- 23957518
TI  - Evaluating and adjusting for premature censoring of progression-free survival.
AB  - The intent-to-treat principle, grouping subjects as they were randomized and
      following all subjects to the endpoint or the end of study, allows valid
      statistical comparisons. Progression-free survival (PFS) has been used as a
      decision-making endpoint in oncology. It can be difficult to have a meaningful
      intent-to-treat analysis of PFS as some studies have extensive loss to follow-up
      for PFS. In the analysis, subjects lost to follow-up for PFS have their PFS times
      censored, with the censoring treated as noninformative. We use remaining overall
      survival to investigate whether premature censoring for PFS is informative and
      the potential bias in treating such censoring as noninformative.

PMID- 23957519
TI  - An analytical approach to assess the predictive value of biomarkers in Phase II
      decision making.
AB  - Early Phase II clinical trials typically have a biomarker as a primary outcome.
      The extent to which a positive result for such a Phase II trial is predictive for
      Phase III success is of obvious concern. In this article we extend existing
      approaches for assessing the probability of success in Phase III. We address the
      case that a dichotomous clinical endpoint of interest is to be measured in Phase
      III. A Beta prior distribution is suggested that quantifies information from both
      the data observed on the biomarker and its predictive accuracy. Based on the
      quantification of the impact of the predictive ability of biomarkers, it is shown
      that the predictive quality of a biomarker needs to be substantial to support the
      full development decision. The approach is illustrated with a practical example.
      A simulation study is presented to illustrate the findings more generally.

PMID- 23957520
TI  - An adaptive two-stage dose-response design method for establishing proof of
      concept.
AB  - We propose an adaptive two-stage dose-response design where a prespecified
      adaptation rule is used to add and/or drop treatment arms between the stages. We
      extend the multiple comparison procedures-modeling (MCP-Mod) approach into a two
      stage design. In each stage, we use the same set of candidate dose-response
      models and test for a dose-response relationship or proof of concept (PoC) via
      model-associated statistics. The stage-wise test results are then combined to
      establish "global" PoC using a conditional error function. Our simulation studies
      showed good and more robust power in our design method compared to conventional
      and fixed designs.

PMID- 23957521
TI  - Joint modeling of clinical efficacy and safety with an application to diabetes
      studies.
AB  - The purpose of drug development is to evaluate a drug's efficacy and safety
      profile. For a personalized medicine, it is important for patients and health
      care providers to understand the efficacy and safety trade-off when selecting a
      dose for a patient. In this article, we propose three different methods for
      jointly modeling the clinical safety and efficacy endpoints. These three methods
      model the correlation relationship in three different ways: modeling the joint
      distribution by a copula method, modeling conditional distributions, and modeling
      their correlations through individual means by a hierarchical model. We compare
      these three methods through simulations and apply these methods to a data set
      from a diabetes study.

PMID- 23957522
TI  - A comparison of bias-corrected covariance estimators for generalized estimating
      equations.
AB  - Although asymptotically the sandwich covariance estimator is consistent and
      robust with respect to the selection of the working correlation matrix, when the
      sample size is small, its bias may not be negligible. This article compares the
      small sample corrections for the sandwich covariance estimator as well as the
      inferential procedures proposed by Mancl and DeRouen ( 2001 ), Kauermann and
      Carroll ( 2001 ), Fay and Graubard ( 2001 ), and Fan et al. ( 2012 ). Simulation
      studies show that when using a maximum likelihood method to estimate the
      covariance parameters and using the between-within method for the denominator
      degrees of freedom when making inference, the Kauermann and Carroll method is
      preferred in the investigated balanced logistic regression and the Mancl and
      DeRouen and Fan et al. methods are preferred in the investigated proportional
      odds model. A collagen-induced arthritis study is employed to demonstrate the
      application of the methods.

PMID- 23957523
TI  - Decision making from Phase II to Phase III and the probability of success:
      reassured by "assurance"?
AB  - With Phase III failure rates of 50%, better ways of predicting late-stage success
      are needed. One concept that has been used is "assurance." Rather than
      conventional power calculations hypothesizing a known effect of a drug, assurance
      provides an expected power calculation based on some prior distribution for the
      treatment effect. It therefore has appeal in Phase III planning and decision
      making, especially when the prior is based on Phase II data. However, assurance
      has counterintuitive properties that can serve to confuse and concern the
      nonstatistician. Appreciation of these properties is helpful to ensure an
      informed use of assurance in strategic drug development.

PMID- 23957527
TI  - A survey on the use of outcome measures by musculoskeletal physiotherapist's in
      India.
AB  - In recent times, there has been great pressure on physiotherapists to become
      accountable for their practices and to provide evidence for effectiveness of
      their treatment. Therefore, it has become necessary to integrate standardised
      outcome measures (OMs) into clinical practice and boost evidence-based practice.
      The aim of this study was to determine the extent of use of outcome measures
      among physiotherapists in India and to identify the commonly used measures. A
      survey was conducted using a questionnaire consisting of 23 closed-ended
      questions. It was administered face-to-face and via email to Indian
      physiotherapists working with musculoskeletal patients. The response rate was 54%
      (n = 81). The results indicated 80% of the respondents used OMs with impairment
      based measures being the most commonly used. Education qualifications, years of
      work experience and workplace setting were not significantly associated with
      utilisation of OMs. Various benefits and barriers to use of OMs were also
      identified. The findings of this study give insight into possible changes that
      could be incorporated in clinical practice and educational system for developing
      a standardised level of assessing patients and to tailor future implementation
      strategies.

PMID- 23957526
TI  - Gut-directed hypnotherapy significantly augments clinical remission in quiescent
      ulcerative colitis.
AB  - BACKGROUND: Psychotherapy is not routinely recommended for in ulcerative colitis
      (UC). Gut-directed hypnotherapy (HYP) has been linked to improved function in the
      gastrointestinal tract and may operate through immune-mediated pathways in
      chronic diseases. AIMS: To determine the feasibility and acceptability of HYP and
      estimate the impact of HYP on clinical remission status over a 1-year period in
      patients with an historical flare rate of 1.3 times per year. METHODS: A total of
      54 patients were randomised at a single site to seven sessions of gut-directed
      HYP (n = 26) or attention control (CON; n = 29) and followed for 1 year. The
      primary outcome was the proportion of participants in each condition that had
      remained clinically asymptomatic (clinical remission) through 52 weeks post
      treatment. RESULTS: One-way analysis of variance comparing HYP and CON subjects
      on number of days to clinical relapse favoured the HYP condition [F = 4.8 (1,
      48), P = 0.03] by 78 days. Chi-squared analysis comparing the groups on
      proportion maintaining remission at 1 year was also significant [chi2(1) = 3.9, P
      = 0.04], with 68% of HYP and 40% of CON patients maintaining remission for 1
      year. There were no significant differences between groups over time in quality
      of life, medication adherence, perceived stress or psychological factors.
      CONCLUSION: This is the first prospective study that has demonstrated a
      significant effect of a psychological intervention on prolonging clinical
      remission in patients with quiescent ulcerative colitis (Clinical Trial #
      NCT00798642).

PMID- 23957528
TI  - Unusual enzymatic glycoside cleavage mechanisms.
AB  - Over the sixty years since Koshland initially formulated the classical mechanisms
      for retaining and inverting glycosidases, researchers have assembled a large body
      of supporting evidence and have documented variations of these mechanisms.
      Recently, however, researchers have uncovered a number of completely distinct
      mechanisms for enzymatic cleavage of glycosides involving elimination and/or
      hydration steps. In family GH4 and GH109 glycosidases, the reaction proceeds via
      transient NAD(+)-mediated oxidation at C3, thereby acidifying the proton at C2
      and allowing for elimination across the C1-C2 bond. Subsequent Michael-type
      addition of water followed by reduction at C3 generates the hydrolyzed product.
      Enzymes employing this mechanism can hydrolyze thioglycosides as well as both
      anomers of activated substrates. Sialidases employ a conventional retaining
      mechanism in which a tyrosine functions as the nucleophile, but in some cases
      researchers have observed off-path elimination end products. These reactions
      occur via the normal covalent intermediate, but instead of an attack by water on
      the anomeric center, the catalytic acid/base residue abstracts an adjacent
      proton. These enzymes can also catalyze hydration of the enol ether via the
      reverse pathway. Reactions of alpha-(1,4)-glucan lyases also proceed through a
      covalent intermediate with subsequent abstraction of an adjacent proton to give
      elimination. However, in this case, the departing carboxylate "nucleophile"
      serves as the base in a concerted but asynchronous syn-elimination process. These
      enzymes perform only elimination reactions. Polysaccharide lyases, which act on
      uronic acid-containing substrates, also catalyze only elimination reactions.
      Substrate binding neutralizes the charge on the carboxylate, which allows for
      abstraction of the proton on C5 and leads to an elimination reaction via an E1cb
      mechanism. These enzymes can also cleave thioglycosides, albeit slowly. The
      unsaturated product of polysaccharide lyases can then serve as a substrate for a
      hydration reaction carried out by unsaturated glucuronyl hydrolases. This
      hydration is initiated by protonation at C4 and proceeds in a Markovnikov fashion
      rather than undergoing a Michael-type addition, giving a hemiketal at C5. This
      hemiketal then undergoes a rearrangement that results in cleavage of the anomeric
      bond. These enzymes can also hydrolyze thioglycosides efficiently and slowly turn
      over substrates with inverted anomeric configuration. The mechanisms discussed in
      this Account proceed through transition states that involve either positive or
      negative charges, unlike the exclusively cationic transition states of the
      classical Koshland retaining and inverting glycosidases. In addition, the
      distribution of this charge throughout the substrate can vary substantially. The
      nature of these mechanisms and their transition states means that any inhibitors
      or inactivators of these unusual enzymes probably differ from those presently
      used for Koshland retaining or inverting glycosidases. 

PMID- 23957529
TI  - Clinical observation on the efficacy of CyberKnife for primary or metastatic
      retroperitoneal tumours.
AB  - The aim of the paper is to evaluate the efficacy of CyberKnife(r) for the
      treatment of primary or metastatic retroperitoneal tumours. Twenty-eight patients
      were treated. The prescription isodose line (median, 78%; range, 70-84%) covered
      the planning target volume at a total dose of 2000-6000 cGy (median, 4500 cGy)
      and a biologically effective dose of 3750-10,080 cGy (median, 7680 cGy) in 2-10
      fractions (median, five fractions). The results showed that the complete
      response, partial response, stable disease, and progressive disease rates were
      43% (12/28), 36% (10/28), 18% (5/28), and 4% (1/28) respectively. The overall
      response rate was 96%. The 1-, 2- and 3-year local control rates were 92%, 86%,
      and 86% respectively. The 1-, 2- and 3-year overall survival rates were 60%, 49%,
      and 49% respectively. No significant difference was found between local
      progression-free survival and overall survival. Moreover, if a patient only had
      metastases in the retroperitoneum and local control was effective, there was no
      significant difference between local progression-free survival and overall
      progression-free survival. In conclusion, CyberKnife treatment for
      retroperitoneal tumours resulted in high response rates with minimal side
      effects. All radiation-induced side effects were well tolerated.

PMID- 23957530
TI  - Fast chemical imaging at high spatial resolution by laser ablation inductively
      coupled plasma mass spectrometry.
AB  - In recent years, chemical imaging was prognosticated to become one of the key
      analytical applications for laser ablation inductively coupled plasma mass
      spectrometry (LA-ICP-MS). However, moderate spatial resolution and the associated
      measurement time required for a larger sampling area, have restricted this
      versatile, high sensitivity technique from being routinely used in two
      dimensional chemical imaging. This work describes the development and
      investigation of a low dispersion sample chamber (tube cell), which allows
      improvement of the imaging capabilities by reduction of the single LA shot
      duration to 30 ms (full width at 1% maximum). The new tube cell is based on a
      constant laminar flow and a well-controlled delivery of the laser-ablated aerosol
      into the transport system, leading to minimized tailing of the aerosol washout
      and helping to separate the signals even at repetition rates as high as 20-30 Hz.
      To demonstrate the improved imaging capabilities, microstructured metallic thin
      film patterns were analyzed at a spatial resolution of a few micrometers. The LA
      ICP-MS results obtained were comparable to Synchrotron-based micro-X-ray
      fluorescence (SR-microXRF). The suitability of the newly designed cell for
      multielement acquisitions was demonstrated using a simultaneous ICP-Mattauch
      Herzog-MS. Finally, the novel laser ablation cell was applied to image the
      distribution of a metal-tagged biomarker in a thin section of breast cancer
      tissue. This application demonstrates that the technique is able to produce
      subcellular (~1 MUm) spatial resolution, which is crucial for morphological
      assessment in cancer diagnostics.

PMID- 23957531
TI  - Comparison of the mechanical properties of self-assembled Langmuir monolayers of
      nanoparticles and phospholipids.
AB  - Nanoparticles with hydrophobic capping ligands and amphiphilic phospholipids are
      both found to self-assemble into monolayer films when deposited on the air/water
      interface. By separately measuring the anisotropic stress response of these films
      under uniaxial compression, we obtain both the 2D compressive and shear moduli of
      a range of different thin nanoparticle and phospholipid films. The compressive
      moduli of both nanoparticle and lipid films in the solid phase are on the same
      order of magnitude, whereas the shear moduli of the lipid films are found to be
      significantly lower. Additionally, the moduli of the nanoparticle films depended
      substantially on the polydispersity of the constituent particles-broader size
      distribution lowered the stiffness of the nanoparticle film. 

PMID- 23957532
TI  - Consequential environmental and economic life cycle assessment of green and gray
      stormwater infrastructures for combined sewer systems.
AB  - A consequential life cycle assessment (LCA) is conducted to evaluate the trade
      offs between water quality improvements and the incremental climate, resource,
      and economic costs of implementing green (bioretention basin, green roof, and
      permeable pavement) versus gray (municipal separate stormwater sewer systems,
      MS4) alternatives of stormwater infrastructure expansions against a baseline
      combined sewer system with combined sewer overflows in a typical Northeast US
      watershed for typical, dry, and wet years. Results show that bioretention basins
      can achieve water quality improvement goals (e.g., mitigating freshwater
      eutrophication) for the least climate and economic costs of 61 kg CO2 eq. and $98
      per kg P eq. reduction, respectively. MS4 demonstrates the minimum life cycle
      fossil energy use of 42 kg oil eq. per kg P eq. reduction. When integrated with
      the expansion in stormwater infrastructure, implementation of advanced wastewater
      treatment processes can further reduce the impact of stormwater runoff on aquatic
      environment at a minimal environmental cost (77 kg CO2 eq. per kg P eq.
      reduction), which provides support and valuable insights for the further
      development of integrated management of stormwater and wastewater. The
      consideration of critical model parameters (i.e., precipitation intensity, land
      imperviousness, and infrastructure life expectancy) highlighted the importance
      and implications of varying local conditions and infrastructure characteristics
      on the costs and benefits of stormwater management. Of particular note is that
      the impact of MS4 on the local aquatic environment is highly dependent on local
      runoff quality indicating that a combined system of green infrastructure prior to
      MS4 potentially provides a more cost-effective improvement to local water
      quality. 

PMID- 23957533
TI  - Rotationally-resolved spectroscopy of the donor bending mode of (D2O)2.
AB  - High-resolution spectra of the intramolecular bending modes of deuterated water
      dimer, (D2O)2, have been measured using a quantum cascade laser based cavity
      ringdown spectrometer. Two perpendicular bands have been observed and are
      assigned as the K(a) = 1 <- 0 and K(a) = 2 <- 1 bands of the bending mode of the
      hydrogen bond donor. The tunneling splittings in the complex are well-resolved,
      and it is found that excitation of the donor bend has little effect on tunneling
      of the hydrogen bond acceptor, but causes significant perturbations on the
      tunneling motion which exchanges the roles of hydrogen bond donor and acceptor.
      The presence of this perturbation has prevented a detailed assignment of the
      tunneling levels in the excited state at this time. An accurate value for the
      band center of the donor bend is calculated to be 1182.2 cm(-1), which is in good
      agreement with previous theoretical calculations performed on an ab initio
      potential energy surface.

PMID- 23957534
TI  - Synergy of non-antibiotic drugs and pyrimidinethiol on gold nanoparticles against
      superbugs.
AB  - Co-presenting non-antibiotic drugs and pyrimidinethiol on gold nanoparticles
      (NPs) can generate broad-spectrum antibacterial and bactericidal activities
      against superbugs. Dimethylbiguanide (metformin), an anti-hyperglycemic drug,
      shows the best enhanced activity via increasing the ability to compromise
      bacterial cell walls. Synergistic effects are also reflected in the eradicating
      biofilm cells. Our findings suggest a large chemical space to develop new
      antibacterial materials to treat superbugs. 

PMID- 23957535
TI  - Effects of pistachio by-products in replacement of alfalfa hay on populations of
      rumen bacteria involved in biohydrogenation and fermentative parameters in the
      rumen of sheep.
AB  - The objective of this study was to investigate the effect of sundried pistachio
      by-products (PBP) as a replacement of alfalfa hay (AH) on blood metabolites,
      rumen fermentation and populations of rumen bacteria involved in biohydrogenation
      (BH) in Baluchi sheep. Four adult male Baluchi sheep (41 +/- 1.3 kg, BW) fitted
      with ruminal cannulae were randomly assigned to four experimental diets in a 4 *
      4 Latin square design. The dietary treatments were as follows: (i) control, (ii)
      12% PBP (0.33 of AH in basal diet replaced by PBP), (iii) 24% PBP (0.66 of AH in
      basal diet replaced by PBP) and (iv) 36% PBP (all of AH in basal diet replaced by
      PBP). The basal diet was 360 g/kg dry matter (DM) alfalfa hay, 160 g/kg DM wheat
      straw and 480 g/kg DM concentrate. The trial consisted of four periods, each
      composed of 16 days adaptation and 4 days data collection including measurement
      of blood metabolites, rumen fermentation and population of bacteria. No
      differences were observed in rumen pH among the treatments, while rumen ammonia-N
      concentrations were decreased (p< 0.05) with increasing PBP by up to 36% DM of
      the diets. Using of 36% PBP in the diet reduced (p < 0.05) total volatile fatty
      acids (VFA) concentrations and the molar proportion of acetate, while the
      concentration of propionate, butyrate and acetate to propionate ratio were
      similar to all other treatments. The concentration of blood urea nitrogen (BUN)
      decreased (p < 0.01) with increasing PBP by up to 36% DM in the diets of sheep.
      However, other blood metabolites were not affected by the experimental diets. It
      was concluded that PBP in replacement of AH had no effects on the relative
      abundance of Butyrivibrio fibrisolvens and Butyrivibrio proteoclasticus in
      relation to the control diet.

PMID- 23957536
TI  - Culture confirmation of tuberculosis cases in Birmingham, UK.
AB  - BACKGROUND: The proportion of culture-confirmed tuberculosis (TB) cases in
      Birmingham had gradually decreased to less than 65% in 2008. Reasons for this
      were unclear, therefore this study assessed diagnostic methods used for
      confirming TB and reviewed factors involved in positive culture. METHODS: A cross
      sectional study was carried out. A list of notified TB cases for Birmingham in
      those aged 16 y and over in 2009 was collated. Where no positive culture was
      recorded, further data were collected from hospital databases and case notes.
      RESULTS: Of 449 TB cases, 419 (93%) had samples taken for culture testing. Of all
      cases, 309 (69%) were confirmed by culture testing; of those receiving culture
      testing, 73% were confirmed. Pulmonary TB was identified as a predictor of
      positive culture in both the unadjusted and adjusted analyses: odds ratio (OR)
      2.05, 95% confidence interval (CI) 1.32-3.19, and OR 2.32, 95% CI 1.29-4.17,
      respectively. Gender, age, ethnicity, UK born, and treatment delay were not
      significantly associated with positive culture. Of 140 cases not confirmed by
      culture, 129 (92%) had their diagnosis supported by at least one other test.
      CONCLUSION: The vast majority of TB cases had microbiological specimens taken to
      help confirm the disease. Furthermore, culture confirmation rates in Birmingham
      were meeting national targets in 2009. However culture confirmation rates were
      significantly lower in extrapulmonary TB, therefore further work is suggested in
      this group. The role of other investigations (e.g. interferon-gamma release assay
      (IGRA), Mantoux) is unclear. Further collaboration between clinicians,
      histopathologists, and microbiologists is advised to ensure samples are sent
      appropriately and culture confirmation is optimized.

PMID- 23957537
TI  - Oral human papillomavirus prevalence in high school students of one municipality
      in Sweden.
AB  - The rise in human papillomavirus (HPV) infection has been suggested to be
      responsible for the increased incidence of oropharyngeal cancer in the Western
      world. This has boosted interest in oral HPV prevalence and whether HPV vaccines
      can prevent oral HPV infection. In a previous study we showed oral HPV prevalence
      to be almost 10% in youth aged 15-23 y attending a youth clinic in Stockholm,
      Sweden. However, this may not be a generalizable sample within the Swedish
      population. Therefore, mouthwashes were used to investigate oral HPV prevalence
      in 335 Swedish high school students aged 17-21 y (median age 18 y), from 1
      municipality with 140,000 inhabitants. The presence of HPV DNA in the oral
      samples, as examined by a Luminex-based assay, was significantly lower in this
      cohort, only 1.8% (3.1% in females and 0.6% in males), as compared to our
      previous study.

PMID- 23957538
TI  - Splenic infarction as a rare complication of infectious mononucleosis due to
      Epstein-Barr virus infection in a patient with no significant comorbidity: case
      report and review of the literature.
AB  - We report the case of a 17-y-old boy diagnosed with infectious mononucleosis due
      to Epstein-Barr virus infection who complained of left upper quadrant pain. A
      magnetic resonance imaging scan showed a splenic infarct in the enlarged spleen.
      Other causes of splenic infarction were excluded. Thus, infectious mononucleosis
      may cause splenic infarction in patients without other comorbidities.

PMID- 23957539
TI  - Recurrent Plasmodium vivax malaria due to dose-dependent primaquine resistance: a
      case report.
AB  - The ability of Plasmodium vivax to relapse is a challenge to its management.
      Primaquine is the only drug licensed for the eradication of hypnozoites. We
      report the case of a non-immune traveller, who required high dosage primaquine
      treatment to obtain radical cure of vivax malaria, emphasizing the importance of
      country-specific and weight-based dosing of primaquine.

PMID- 23957540
TI  - Detection of methicillin-resistant and methicillin-susceptible Staphylococcus
      aureus colonization of healthy military personnel by traditional culture, PCR,
      and mass spectrometry.
AB  - BACKGROUND: Methicillin-resistant (MRSA) and methicillin-susceptible (MSSA)
      Staphylococcus aureus colonization is associated with increased rates of
      infection. Rapid and reliable detection methods are needed to identify
      colonization of nares and extra-nare sites, particularly given recent reports of
      oropharynx-only colonization. Detection methods for MRSA/MSSA colonization
      include culture, PCR, and novel methods such as PCR/electrospray ionization time
      of-flight mass spectrometry (ESI-TOF-MS). METHODS: We evaluated 101 healthy
      military members for S. aureus colonization in the nares, oropharynx, axilla, and
      groin, using CHROMagar S. aureus medium and Xpert SA Nasal Complete PCR for
      MRSA/MSSA detection. The same subjects were screened in the nares, oropharynx,
      and groin using PCR/ESI-TOF-MS. RESULTS: By culture, 3 subjects were MRSA
      colonized (all oropharynx) and 34 subjects were MSSA-colonized (all 4 sites). PCR
      detected oropharyngeal MRSA in 2 subjects, which correlated with culture
      findings. By PCR, 47 subjects were MSSA-colonized (all 4 sites); however, 43
      axillary samples were invalid, 39 of which were associated with deodorant/anti
      perspirant use (93%, p < 0.01). By PCR/ESI-TOF-MS, 4 subjects were MRSA
      colonized, 2 in the nares and 2 in the oropharynx; however, neither of these
      correlated with positive MRSA cultures. Twenty-eight subjects had MSSA by PCR/ESI
      TOF-MS, and 41 were found to have possible MRSA (S. aureus with mecA and
      coagulase-negative Staphylococcus (CoNS)). CONCLUSION: The overall 3% MRSA
      colonization rate is consistent with historical reports, but the oropharynx-only
      colonization supports more recent findings. In addition, the use of
      deodorant/anti-perspirant invalidated axillary PCR samples, limiting its utility.
      Defining MRSA positivity by PCR/ESI-TOF-MS is complicated by co-colonization of
      S. aureus with CoNS, which can also carry mecA.

PMID- 23957541
TI  - Primary nasal tuberculosis during anti-tumour necrosis factor alpha treatment of
      a patient with rheumatoid arthritis.
AB  - Anti-tumour necrosis factor alpha (anti-TNFalpha) therapy is increasingly used in
      several inflammatory disease processes, including rheumatoid arthritis. However
      it has a significant potential for adverse events, such as reactivation of latent
      tuberculosis, which is frequently found in disseminated or extrapulmonary forms.
      We present a rare case of primary nasal tuberculosis within the context of anti
      TNFalpha therapy for rheumatoid arthritis. To our knowledge, this is the first
      reported case of primary nasal tuberculosis in a patient with rheumatoid
      arthritis receiving anti-TNFalpha therapy.

PMID- 23957542
TI  - What is in this issue.

PMID- 23957544
TI  - Interventions for the prevention of postoperative ear discharge after insertion
      of ventilation tubes (grommets) in children.

PMID- 23957545
TI  - Prophylactic ear drops should not be used routinely to prevent postoperative,
      ventilation tubes otorrhoea.

PMID- 23957546
TI  - Response to Rimmer and Lund regarding 'inferior turbinate mucosal graft combined
      with radio frequency for nasal hereditary haemorrhagic telangiectasia'.

PMID- 23957547
TI  - Re: What I do if things go wrong: up-to-date expert opinion referencing the best
      evidence available on intraoperative cerebrospinal fluid leak during endoscopic
      sinus surgery.

PMID- 23957548
TI  - Re: Adult and paediatric tonsillectomy: a two-cycle audit of Scottish
      Intercollegiate Guidelines Network 117 in a total of one hundred and sixty-nine
      patients.

PMID- 23957549
TI  - Re. Role of Buteyko breathing tecnique in asthmatics with nasal symptoms.

PMID- 23957550
TI  - New oral anticoagulants and risks in ENT.

PMID- 23957551
TI  - Should we still be using bismuth iodoform paraffin paste-impregnated gauze as an
      ear canal dressing following ear surgery?

PMID- 23957552
TI  - Suction aural snare.

PMID- 23957554
TI  - Characteristics of three listeriaphages isolated from New Zealand seafood
      environments.
AB  - AIM: To isolate and characterize listeriaphages from seafood environments.
      METHODS AND  RESULTS: Listeriaphages (phages) isolated from seafood environments
      were distinguished by physical and biological techniques including restriction
      digestion of phage DNA. Three phages belonged to order Caudovirales and showed
      psychrotrophic characteristics. The phages had broad host ranges against 23
      Listeria strains by productive infection or at least by adsorption. At 15 +/- 1
      degrees C, adsorption rate constants of the three phages ranged from 8.93 * 10(
      9) to 3.24 * 10(-11 ) ml min(-1) across different Listeria monocytogenes strains.
      In indicator hosts, the mean burst sizes of phages LiMN4L, LiMN4p and LiMN17 were
      c. 17, 17 and 11 plaque-forming units (PFU) per cell, respectively, at 15 +/- 1
      degrees C. The respective latent periods were c. 270 min for phages LiMN4p and
      LiMN17, whereas for phage LiMN4L, it was c. 240 min. CONCLUSIONS: The three
      virulent psychrotrophic phages isolated from seafood-processing environments had
      broad host ranges and low productive replication. These characteristics suggest
      that the phages may be suitable as passive biocontrol agents against seafood
      borne L. monocytogenes. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first
      report on the isolation of autochthonous virulent listeriaphages from seafood
      processing environments and information on single-step replication and adsorption
      characteristics of such listeriaphages.

PMID- 23957555
TI  - Synthesis of hyperbranched polypeptide and PEO block copolymer by consecutive
      thiol-yne chemistry.
AB  - Hyperbranched poly(epsilon-benzyloxycarbonyl-L-lysine) (HPlys) with multiple
      alkyne peripheries was synthesized through the click polycondensation of an AB2
      type Plys macromonomer with alpha-thiol and omega-alkyne terminal groups (thiol
      is the A unit, and each pi bond in alkyne is the B unit), and the resulting HPlys
      was further conjugated with thiol-termined poly(ethylene oxide) (PEO) to generate
      HPlys-b-PEO block copolymer by consecutive thiol-yne chemistry. Their molecular
      structures and physical properties were characterized in detail by FT-IR, (1)H
      NMR, gel permeation chromatography, differential scanning calorimetry, wide-angle
      X-ray diffraction, and polarized optical microscopy. HPlys and HPlys-b-PEO mainly
      assumed an alpha-helix conformation similar to the linear precursors, while the
      liquid crystalline phase transition of Plys segment disappeared within HPlys and
      HPlys-b-PEO. HPlys-b-PEO self-assembled into nearly spherical micelles in aqueous
      solution, while it gave a 5-fold lower critical aggregation concentration (8.9 *
      10(-3) mg/mL) than a linear counterpart (4.5 * 10(-2) mg/mL), demonstrating a
      dendritic topology effect. Compared with a linear counterpart, HPlys-b-PEO gave a
      higher drug-loading capacity and efficiency for the anticancer drug doxorubicin
      (DOX) and a slower drug-release rate with an improved burst-release profile,
      enabling them useful for drug delivery systems. Importantly, this work provides a
      versatile strategy for the synthesis of hyperbranched polypeptides and related
      block copolymers by utilizing thiol-yne chemistry.

PMID- 23957556
TI  - Retention force assessment in conical crowns in different material combinations.
AB  - The puprose of this study was to evaluate retention force of conical double
      crowns in two material connections: gold casting alloy/gold casting alloy and
      gold casting alloy/gold electroforming alloy. 12 crown pairs of both material
      connections with the cone angles of 2 degrees , 4 degrees  and 6 degrees  were
      made. Experiment of 10.000 in-and-out cycles was performed using a new device
      which allows the retentive force to be measured in continuous way without
      necessity of moving the samples to another device. It has been found that the
      higher the retentive force values, the lower the cone angle. Dispersion of the
      retention value was similar in both groups, but when cone angle was 2 degrees  or
      4 degrees , stability of retention force with the passage of time was higher in
      combinations with electroformed copings. The optimum solution was the cast
      alloy/cast alloy connection but only with cone angle 6 degrees . However,
      retentive values seem to be too low to achieve proper retention of dentures.

PMID- 23957557
TI  - Role of exercise-induced reactive oxygen species in the modulation of heat shock
      protein response.
AB  - The multiple roles that have been associated with heat shock proteins (HSPs),
      inside and outside cells are remarkable. HSPs have been found to play a
      fundamental role in multiple stress conditions and to offer protection from
      subsequent insults. Exercise, because of the physiological stresses associated
      with it, is one of the main stimuli associated with a robust increase of
      different HSPs in several tissues. Given the combination of physiological
      stresses induced by exercise, and the 'cross-talk' that occurs between signaling
      pathways in different tissues, it is likely that exercise induces the HSP
      expression through a combination of 'stressors', among which reactive oxygen
      species (ROS) could play a major role. Indeed, although an imbalance between ROS
      production and antioxidant levels results in oxidative stress, causing damage to
      lipids, proteins, and nucleic acids with a possible activation of the programed
      cell death pathway, at moderate concentrations ROS play an important role as
      regulatory mediators in signaling processes. Many of the ROS-mediated responses
      actually protect the cells against oxidative stress and re-establish redox
      homeostasis. The aim of this review is to provide a critical update on the role
      of exercise-induced ROS in the modulation of the HSP's response, focusing on
      experimental results from animal and human studies where the link between redox
      homeostasis and HSPs' expression in different tissues has been addressed.

PMID- 23957558
TI  - Dear-Doctor-Letter Fumaderm(r) - What are the facts?

PMID- 23957560
TI  - Core dimensions of personality broadly account for the link from perceived social
      support to symptoms of depression and anxiety.
AB  - Specific personality traits and poor social support are risk factors for anxiety
      and depression. Little work, however, has considered the effects of social
      support and personality on these aspects of psychopathology simultaneously. We
      examined whether perceived social support mediates the effects of core
      personality domains on symptoms of anxiety and depression. Measures of
      personality (based on the Five-Factor Model [FFM]), perceived social support, and
      symptoms of depression and anxiety were collected in a large Dutch adult
      population-based sample (n = 555), and, except for depression symptoms, in an
      independent U.S. adult population-based sample (n = 511). Path modeling was used
      to test the effects of FFM traits on symptoms of depression and anxiety, with and
      without the mediation of perceived social support. Social support showed no link
      to symptoms of anxiety and only modest links to symptoms of depression when
      controlling for the FFM traits. Neuroticism had the strongest effect on symptoms
      of both depression and anxiety, with Extraversion also showing links to symptoms
      of depression. Social support has limited influence on symptoms of depression,
      and no effects on anxiety, over and above the effects of personality. Links
      between social support and anxiety/depression may largely reflect influences of
      Neuroticism and Extraversion. 

PMID- 23957562
TI  - Broadening our horizons: seeing beyond the six 'C's to capture the depth of
      mental health nursing.

PMID- 23957559
TI  - The sea lamprey has a primordial accessory olfactory system.
AB  - BACKGROUND: A dual olfactory system, represented by two anatomically distinct but
      spatially proximate chemosensory epithelia that project to separate areas of the
      forebrain, is known in several classes of tetrapods. Lungfish are the earliest
      evolving vertebrates known to have this dual system, comprising a main olfactory
      and a vomeronasal system (VNO). Lampreys, a group of jawless vertebrates, have a
      single nasal capsule containing two anatomically distinct epithelia, the main
      (MOE) and the accessory olfactory epithelia (AOE). We speculated that lamprey AOE
      projects to specific telencephalic regions as a precursor to the tetrapod
      vomeronasal system. RESULTS: To test this hypothesis, we characterized the neural
      circuits and molecular profiles of the accessory olfactory epithelium in the sea
      lamprey (Petromyzon marinus). Neural tract-tracing revealed direct and reciprocal
      connections with the dorsomedial telencephalic neuropil (DTN) which in turn
      projects directly to the dorsal pallium and the rostral hypothalamus. High
      throughput sequencing demonstrated that the main and the accessory olfactory
      epithelia have virtually identical profiles of expressed genes. Real time
      quantitative PCR confirmed expression of representatives of all 3 chemoreceptor
      gene families identified in the sea lamprey genome. CONCLUSION: Anatomical and
      molecular evidence shows that the sea lamprey has a primordial accessory
      olfactory system that may serve a chemosensory function.

PMID- 23957561
TI  - Preoperative core needle biopsy is accurate in determining molecular subtypes in
      invasive breast cancer.
AB  - BACKGROUND: Estrogen receptor (ER), progesterone receptor (PgR), HER2, and Ki67
      have been increasingly evaluated by core needle biopsy (CNB) and are recommended
      for classifying breast cancer into molecular subtypes. However, the concordance
      rate between CNB and open excision biopsy (OEB) has not been well documented.
      METHODS: Patients with paired CNB and OEB samples from Oct. 2009 to Feb. 2012 in
      Ruijin Hospital were included. ER, PgR, HER2, and Ki67 were determined by
      immunohistochemistry (IHC). Patients with HER2 IHC 2+ were further examined by
      FISH. Cutoff value for Ki67 high expression was 14%. Molecular subtypes were
      constructed as follows: Luminal A, Luminal B, Triple Negative, and HER2 positive.
      RESULTS: There were 298 invasive breast cancer patients analyzed. Concordance
      rates for ER, PgR, and HER2 were 93.6%, 85.9%, and 96.3%, respectively. Ki67
      expression was slightly higher in OEB than in CNB samples (29.3% vs. 26.8%, P =
      0.046). Good agreement (kappa = 0.658) was demonstrated in evaluating molecular
      subtypes between CNB and OEB, with a concordance rate of 77.2%. We also used a
      different Ki67 cutoff value (20%) for determining Luminal A and B subtypes in HR
      (hormone receptor) +/HER2- diseases and the overall concordance rate was 79.2%.
      However, using a cut-point of Ki67 either 14% or 20% for both specimens, there
      will be about 14% of HR+/HER2- specimens that are called Luminal A on CNB and
      Luminal B on OEB. CONCLUSION: CNB was accurate in determining ER, PgR, and HER2
      status as well as non-Luminal molecular subtypes in invasive breast cancer. Ki67
      should be retested on OEB samples in HR+/HER2- patients to accurately distinguish
      Luminal A from B tumors.

PMID- 23957563
TI  - Microstructure of the superficial epithelial cells of the human oral mucosa.
AB  - BACKGROUND: The apical cell membrane of the oral mucosa adjacent to the saliva
      interface is thrown into membrane folds, termed microplicae (MPL) with variation
      in morphology. The present study classifies morphological changes undergone by
      MPL into qualitative and quantitative categories. MATERIAL AND METHODS: Oral
      mucosal specimens were obtained from 32 healthy patients. Half of each specimen
      was prepared routinely for light microscopy, and the other part for scanning and
      transmission electron microscopy. Different measurements of cell structure were
      presented: the density of MPL, the width and height of MPL, the width of furrows
      between two adjacent MPL and the distance of the centre of MPL. Morphometric
      measurements were obtained using a semiautomatic ImageJ analysis software (W
      Rasband, National Institutes of Health, Bethesda, MD). RESULTS: Parallel and
      branching MPL was common observation in the area of lining mucosa and in the
      tongue between the filiform papillae. The density of MPL was higher in the cells
      of the buccal mucosa than in the cells of the tongue, 43.69 + 11.43% and 31.68 +
      10.32%, respectively. The difference was significant (p < 0.001). The width of
      MPL was 0.16 um in cells of the buccal mucosa and 0.12 um in cells of the tongue.
      CONCLUSIONS: Our findings support the idea that MPL structure is a determining
      factor for the functionality of the oral epithelium since the values of the MPL
      were kept relatively stable. The role of MPL structure of the oral mucosal cells
      is discussed.

PMID- 23957564
TI  - Quantification of radiation-induced lung damage with CT scans: the possible
      benefit for radiogenomics.
AB  - BACKGROUND: Radiation-induced lung damage (RILD) is an important problem.
      Although physical parameters such as the mean lung dose are used in clinical
      practice, they are not suited for individualised radiotherapy. Objective,
      quantitative measurements of RILD on a continuous instead of on an ordinal, semi
      quantitative, semi-subjective scale, are needed. METHODS: Hounsfield unit (HU)
      changes before versus three months post-radiotherapy were correlated per voxel
      with the radiotherapy dose in 95 lung cancer patients. Deformable registration
      was used to register pre- and post-CT scans and the density increase was
      quantified for various dose bins. The dose-response curve for increased HU was
      quantified using the slope of a linear regression (HU/Gy). The end-point for the
      toxicity analysis was dyspnoea >= grade 2. RESULTS: Radiation dose was linearly
      correlated with the change in HU (mean R(2) = 0.74 +/- 0.28). No differences in
      HU/Gy between groups treated with stereotactic radiotherapy, conventional
      radiotherapy alone, sequential or concurrent chemo- radiotherapy were observed.
      In the whole patient group, 33/95 (34.7%) had dyspnoea >= G2. Of the 48 patients
      with a HU/Gy below the median, 16 (33.3%) developed dyspnoea >= G2, while in the
      47 patients with a HU/Gy above the median, 17 (36.1%) had dyspnoea >= G2 (not
      significant). Individual patients showed a nearly 21-fold difference in
      radiosensitivity, with HU/Gy ranging from 0 to 10 HU/Gy. CONCLUSIONS: HU changes
      identify objectively the whole range of individual radiosensitivity on a
      continuous, quantitative scale. CT density changes may allow more robust and
      accurate radiogenomics studies.

PMID- 23957565
TI  - Automatic delineation for replanning in nasopharynx radiotherapy: what is the
      agreement among experts to be considered as benchmark?
AB  - BACKGROUND AND PURPOSE: Anatomic changes during head and neck radiotherapy
      require replanning. The primary aim of this study is the definition of the
      agreement among experts in the head and neck automatic delineation frame to use
      as benchmark. The secondary goal is to assess the reliability of automatic
      delineation for nasopharynx radiotherapy and time saving. MATERIAL AND METHODS: A
      computed tomography (CT) scan was acquired in 10 nasopharynx patients along
      intensity-modulated radiotherapy (IMRT) treatment for replanning. Deformable
      registration with replanning autocontouring of the structures was performed using
      VelocityAI 2.3(c) software defining Structure Set A. The optimization of these
      contours was obtained through revision by a skilled operator, drawing Structure
      Set B. An ex novo Structure Set C was segmented on the replanning CT-scan by an
      expert delineation team. The mean Dice's Similarity Index (mDSI) was calculated
      between Structure Set A and B, A and C, and between B and C for each volume. All
      segmentation times for organs at risk (OARs) and clinical target volume (CTV)
      were recorded and compared. RESULTS: We validated the replanning autocontoured
      Structure Sets for 10 patients. For volumetric analysis we observed mDSI values
      of 0.87 for the OARs, 0.70 for nodes, 0.90 for CTV in the Structure Set A-B
      comparison and respectively of 0.74, 0.63 and 0.78 for the Structure Set A-C one,
      and 0.78, 0.78 and 0.85 for Structure Set B-C, which represents the existing
      expert based benchmark. We calculated a mean saved time in Structure Set B of 30
      minutes. CONCLUSIONS: Autocontouring procedures offer considerable segmentation
      time saving with acceptable reliability of the contours, even if an independent
      check procedure for their optimization is still required to increase their
      adherence to referential benchmark gold standard among experts, which stands at a
      0.80 DSI value.

PMID- 23957566
TI  - Magnetic resonance imaging for assessment of parametrial tumour spread and
      regression patterns in adaptive cervix cancer radiotherapy.
AB  - PURPOSE: To investigate the impact of magnetic resonance imaging (MRI)
      morphologic differences in parametrial infiltration on tumour response during
      primary radiochemotherapy in cervical cancer. MATERIAL AND METHODS: Eighty-five
      consecutive cervical cancer patients with FIGO stages IIB (n = 59) and IIIB (n =
      26), treated by external beam radiotherapy (+/- chemotherapy) and image-guided
      adaptive brachytherapy, underwent T2-weighted MRI at the time of diagnosis and at
      the time of brachytherapy. MRI patterns of parametrial tumour infiltration at the
      time of diagnosis were assessed with regard to predominant morphology and maximum
      extent of parametrial tumour infiltration and were stratified into five tumour
      groups (TG): 1) expansive with spiculae; 2) expansive with spiculae and
      infiltrating parts; 3) infiltrative into the inner third of the parametrial space
      (PM); 4) infiltrative into the middle third of the PM; and 5) infiltrative into
      the outer third of the PM. MRI at the time of brachytherapy was used for
      identifying presence (residual vs. no residual disease) and signal intensity
      (high vs. intermediate) of residual disease within the PM. Left and right PM of
      each patient were evaluated separately at both time points. The impact of the TG
      on tumour remission status within the PM was analysed using chi(2)-test and
      logistic regression analysis. RESULTS: In total, 170 PM were analysed. The TG 1,
      2, 3, 4, 5 were present in 12%, 11%, 35%, 25% and 12% of the cases, respectively.
      Five percent of the PM were tumour-free. Residual tumour in the PM was identified
      in 19%, 68%, 88%, 90% and 85% of the PM for the TG 1, 2, 3, 4, and 5,
      respectively. The TG 3-5 had significantly higher rates of residual tumour in the
      PM in comparison to TG 1 + 2 (88% vs. 43%, p < 0.01). CONCLUSION: MRI-morphologic
      features of PM infiltration appear to allow for prediction of tumour response
      during external beam radiotherapy and chemotherapy. A predominantly infiltrative
      tumour spread at the time of diagnosis resulted in a significantly higher rate of
      residual tumour in the PM at the time of brachytherapy in comparison to a
      predominantly expansive tumour spread.

PMID- 23957567
TI  - Val66Met polymorphism and serum brain-derived neurotrophic factor in bipolar
      disorder: an open-label trial.
AB  - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is consistently associated
      with acute mood episodes in bipolar disorder, but there is a lack of longitudinal
      data to support this hypothesis. In this 16-week open-label clinical trial, we
      tested the predictive role of BDNF Val66Met polymorphism on serum BDNF levels and
      the relationship of serum BDNF and clinical response in people with bipolar
      disorder during an acute illness episode. METHOD: Sixty-four people with bipolar
      disorder who were medication-free at baseline and in an acute mood episode were
      recruited. They were matched with 64 healthy controls. Clinical evaluation, serum
      BDNF, and BDNF Val66Met polymorphism were determined at baseline, and change in
      serum BDNF was assessed in patients at weeks 2, 4, 8 and 16. RESULTS: There were
      no differences between patients and controls in serum BDNF or in frequencies of
      the BDNF Val66Met polymorphism genotype at baseline. The multivariable model
      showed that Met carriers had a significantly different change in BDNF levels
      compared with Val homozygotes. Not achieving a complete remission was also
      associated with lower prospectively assessed BDNF levels. CONCLUSION: This study
      provides the first longitudinal evidence that both the BDNF Val66Met polymorphism
      and remission status predict change in circulating BDNF levels.

PMID- 23957568
TI  - Singular clues to causality and their use in human causal judgment.
AB  - It is argued that causal understanding originates in experiences of acting on
      objects. Such experiences have consistent features that can be used as clues to
      causal identification and judgment. These are singular clues, meaning that they
      can be detected in single instances. A catalog of 14 singular clues is proposed.
      The clues function as heuristics for generating causal judgments under
      uncertainty and are a pervasive source of bias in causal judgment. More
      sophisticated clues such as mechanism clues and repeated interventions are
      derived from the 14. Research on the use of empirical information and conditional
      probabilities to identify causes has used scenarios in which several of the clues
      are present, and the use of empirical association information for causal judgment
      depends on the presence of singular clues. It is the singular clues and their
      origin that are basic to causal understanding, not multiple instance clues such
      as empirical association, contingency, and conditional probabilities. 

PMID- 23957569
TI  - Meta-analysis: underutilisation and disparities of treatment among patients with
      hepatocellular carcinoma in the United States.
AB  - BACKGROUND: Despite wide availability of treatment options for hepatocellular
      carcinoma (HCC), several studies have suggested underutilisation in clinical
      practice. AIMS: To quantify utilisation rates for HCC treatment among patients
      with HCC in the United States, and to summarise patterns of association between
      utilisation rates and patient socio-demographic characteristics. METHODS: We
      performed a systematic literature review using the Medline database from January
      1989 to March 2013. Two investigators independently extracted data on patient
      populations, study methods and results using standardised forms. Pooled treatment
      rates for any treatment and curative treatment, with 95% confidence intervals,
      were calculated. Prespecified subgroup analysis was performed to identify patient
      level correlates of treatment utilisation. RESULTS: We identified 24 studies that
      met inclusion criteria. The pooled rates of any treatment and curative treatment
      were 52.8% (95% CI 52.2-53.4%) and 21.8% (95% CI 21.4-22.1%) respectively. Among
      patients diagnosed at an early stage, the pooled curative treatment rate was
      59.0% (95% CI 58.1-59.9%). Elderly, non-Caucasians and patients of low
      socioeconomic status had lower treatment rates than their counterparts.
      CONCLUSIONS: Rates of HCC treatment in the United States, including curative
      treatment rates among patients detected at an early stage, are disappointingly
      low. Future efforts should focus on identifying appropriate intervention targets
      to increase treatment rates and reduce socio-demographic disparities.

PMID- 23957570
TI  - Total synthesis of virgatolide B.
AB  - The first total synthesis of the benzannulated spiroketal virgatolide A is
      presented. Key features include sp(3)-sp(2) Suzuki coupling of an
      enantiomerically enriched beta-trifluoroboratoamide and an aryl bromide,
      regioselective intramolecular carboalkoxylation, and a 1,3-anti-selective
      Mukaiyama aldol reaction followed by global deprotection/cyclization with
      regioselectivity governed by internal hydrogen bonding. 

PMID- 23957571
TI  - Acute skin toxicity in Korean breast cancer patients carrying BRCA mutations.
AB  - PURPOSE: In contrast to in vitro studies, most clinical trials testing the
      radiosensitivity of BRCA (Breast cancer susceptibility gene) mutations do not
      find a correlation between BRCA status and enhanced radiosensitivity. These
      trials include different ethnicities, and there is a lack of clinical data on
      BRCA1/2 mutation carriers and radiosensitivity in non-Caucasian patients. The
      goal of this study was to investigate acute skin toxicity, as a part of
      radiosensitivity, in breast cancer patients with BRCA1/2 mutations. MATERIAL AND
      METHODS: BRCA mutation analysis was performed for 213 patients who underwent
      breast-conserving therapy using radiotherapy. Skin toxicity was scored according
      to the Radiation Therapy Oncology Group (RTOG) criteria during treatment and
      during one-month follow-up after radiation therapy. RESULTS: Forty-six patients
      had BRCA1/2 mutations and 57 patients showed higher than grade 2 (RTOG) skin
      toxicity. In multivariate analysis, significant associations were found between
      mean breast volume and acute skin toxicity. BRCA mutation status, however, failed
      to show a significant correlation. CONCLUSIONS: Our results indicate that
      carriers of BRCA1/2 mutations among non-Caucasian breast cancer patients showed
      no enhancement in radiation sensitivity. Multiple genetic markers may be
      correlated with normal tissue responses after radiotherapy. Further studies are
      needed to identify genetic predispositions to normal tissue responses after
      radiotherapy.

PMID- 23957572
TI  - Therapeutic consequences from changing voice ideals (clear to harsh, pleasant to
      jarring): summarizing report on a round-table discussion at the 5th World Voice
      Congress, Luxor, Egypt, 27-31 October 2012.
AB  - Starting out with an attempt to define an 'ideal voice', the discussion moved on
      to the hazards of pop singing, followed by the topics of harsh voices (from the
      desired effects in modern singing expression to devastating clinical cases),
      phoniatric targets (aesthetics and fitness), and, finally, the phoniatricians'
      attitudes comprising acceptance, neglect, and rejection. Therapy should aim at a
      resilient and effective voice regardless of the mere sound, unless the perfection
      of the vocal sound is the ultimate goal. In addition, the panellists agreed that
      voice specialists and all friends of healthy and efficient voices are obliged
      permanently to engage in voice care.

PMID- 23957573
TI  - Artificial photosynthesis: from nanosecond electron transfer to catalytic water
      oxidation.
AB  - Human society faces a fundamental challenge as energy consumption is projected to
      increase due to population and economic growth as fossil fuel resources decrease.
      Therefore the transition to alternative and sustainable energy sources is of the
      utmost importance. The conversion of solar energy into chemical energy, by
      splitting H2O to generate molecular O2 and H2, could contribute to solving the
      global energy problem. Developing such a system will require the combination of
      several complicated processes, such as light-harvesting, charge separation,
      electron transfer, H2O oxidation, and reduction of the generated protons. The
      primary processes of charge separation and catalysis, which occur in the natural
      photosynthetic machinery, provide us with an excellent blueprint for the design
      of such systems. This Account describes our efforts to construct supramolecular
      assemblies capable of carrying out photoinduced electron transfer and to develop
      artificial water oxidation catalysts (WOCs). Early work in our group focused on
      linking a ruthenium chromophore to a manganese-based oxidation catalyst. When we
      incorporated a tyrosine unit into these supramolecular assemblies, we could
      observe fast intramolecular electron transfer from the manganese centers, via the
      tyrosine moiety, to the photooxidized ruthenium center, which clearly resembles
      the processes occurring in the natural system. Although we demonstrated multi
      electron transfer in our artificial systems, the bottleneck proved to be the
      stability of the WOCs. Researchers have developed a number of WOCs, but the
      majority can only catalyze H2O oxidation in the presence of strong oxidants such
      as Ce(IV), which is difficult to generate photochemically. By contrast,
      illumination of ruthenium(II) photosensitizers in the presence of a sacrificial
      acceptor generates [Ru(bpy)3](3+)-type oxidants. Their oxidation potentials are
      significantly lower than that of Ce(IV), but our group recently showed that
      incorporating negatively charged groups into the ligand backbone could decrease
      the oxidation potential of the catalysts and, at the same time, decrease the
      potential for H2O oxidation. This permitted us to develop both ruthenium- and
      manganese-based WOCs that can operate under neutral conditions, driven by the
      mild oxidant [Ru(bpy)3](3+). Many hurdles to the development of viable systems
      for the production of solar fuels remain. However, the combination of important
      features from the natural photosynthetic machinery and novel artificial
      components adds insights into the complicated catalytic processes that are
      involved in splitting H2O. 

PMID- 23957574
TI  - Women's attitudes towards mechanisms of action of birth control methods: a cross
      sectional study in five European countries.
AB  - AIMS AND OBJECTIVES: To assess women's attitudes towards the mechanisms of action
      of birth control methods. BACKGROUND: When addressing women's knowledge of and
      attitudes towards birth control methods, researchers frequently focus on side
      effects, effectiveness or correct use. Women's opinions about mechanisms of
      action have been much less investigated, and research is usually concentrated on
      the EC pill. DESIGN: Cross-sectional study. METHODS: Women, aged 18-49, from
      Germany, France, the UK, Sweden and Romania were randomly selected (n = 1137).
      They were asked whether they would use a method that may work after fertilisation
      or after implantation and whether they would continue using it after learning it
      may have such effects. Logistic regression was performed to evaluate the
      influence of certain characteristics on women's attitudes. RESULTS: Almost half
      of women in Romania and Germany would not use methods with postfertilisation
      effects, while the lowest percentages were found in Sweden and in France.
      Regarding methods with postimplantation effects, higher percentages were found in
      all the countries. Highly educated women and those using a highly effective
      method were more likely to use methods with postfertilisation effects. On the
      contrary, married women, those who stated that human life begins at fertilisation
      and women with middle/high religiosity were less likely to consider using methods
      that may act after fertilisation. CONCLUSIONS: One-third of European women
      reported that they would not consider using a method that may have
      postfertilisation effects. RELEVANCE TO CLINICAL PRACTICE: Given that
      postfertilisation effects may not be acceptable to some women, informing them of
      which methods may have these effects is essential to obtaining complete informed
      consent and to promoting women's autonomy.

PMID- 23957575
TI  - Application of peptide gemini surfactants as novel solubilization surfactants for
      photosystems I and II of cyanobacteria.
AB  - We designed novel peptide gemini surfactants (PG-surfactants), DKDKC12K and
      DKDKC12D, which can solubilize Photosystem I (PSI) of Thermosynecoccus elongatus
      and Photosystem II (PSII) of Thermosynecoccus vulcanus in an aqueous buffer
      solution. To assess the detailed effects of PG-surfactants on the original
      supramolecular membrane protein complexes and functions of PSI and PSII, we
      applied the surfactant exchange method to the isolated PSI and PSII.
      Spectroscopic properties, light-induced electron transfer activity, and dynamic
      light scattering measurements showed that PSI and PSII could be solubilized not
      only with retention of the original supramolecular protein complexes and
      functions but also without forming aggregates. Furthermore, measurement of the
      lifetime of light-induced charge-separation state in PSI revealed that both
      surfactants, especially DKDKC12D, displayed slight improvement against thermal
      denaturation below 60  degrees C compared with that using beta-DDM. This degree
      of improvement in thermal resistance still seems low, implying that the peptide
      moieties did not interact directly with membrane protein surfaces. By conjugating
      an electron mediator such as methyl viologen (MV(2+)) to DKDKC12K (denoted MV
      DKDKC12K), we obtained derivatives that can trap the generated reductive
      electrons from the light-irradiated PSI. After immobilization onto an indium tin
      oxide electrode, a cathodic photocurrent from the electrode to the PSI/MV
      DKDKC12K conjugate was observed in response to the interval of light irradiation.
      These findings indicate that the PG-surfactants DKDKC12K and DKDKC12D provide not
      only a new class of solubilization surfactants but also insights into designing
      other derivatives that confer new functions on PSI and PSII. 

PMID- 23957576
TI  - Droplet-interfaced microchip and capillary electrophoretic separations.
AB  - Both capillary and chip-based electrophoresis are powerful separation methods
      widely used for the separation of complex analytical mixtures in the fields of
      genomics, proteomics, metabolomics, and cellular analysis. However their utility
      as basic tools in high-throughput analysis and multidimensional separations has
      been hampered by inefficient or biased sample injection methods. Herein, we
      address this problem through the development of a simple separation platform that
      incorporates droplet-based microfluidic module for the encapsulation of analytes
      prior to the analytical separation. This method allows for the precise and
      reproducible injection of pL to nL volume isolated plugs into an electrophoretic
      separation channel. The developed platform is free from inter sample
      contamination, allows for small sample size, high-throughput analysis, and can
      provide quantitative analytical information. 

PMID- 23957577
TI  - Redox responsive release of hydrophobic self-healing agents from polyaniline
      capsules.
AB  - Redox-responsive nanocapsules consisting of conductive polyaniline and
      polypyrrole shells were successfully synthesized by using the interface of
      miniemulsion droplets as a template for oxidative polymerizations. The redox
      properties of the capsules were investigated by optical spectroscopies, electron
      microscopy, and cyclic voltammetry. Self-healing (SH) chemicals such as
      diglycidyl ether or dicarboxylic acid terminated polydimethylsiloxane (PDMS-DE or
      PDMS-DC) were encapsulated into the nanocapsules during the miniemulsion process
      and their redox-responsive release was monitored by (1)H NMR spectroscopy. The
      polyaniline capsules exhibited delayed release under oxidation and rapid release
      under reduction, which make them promising candidates for anticorrosion
      applications. 

PMID- 23957578
TI  - Direct evaluation of in situ biodegradation in Athabasca oil sands tailings ponds
      using natural abundance radiocarbon.
AB  - Compound-specific stable (delta(13)C) and radiocarbon (Delta(14)C) isotopes of
      phospholipid fatty acids (PLFAs) were used to evaluate carbon sources utilized by
      the active microbial populations in surface sediments from Athabasca oil sands
      tailings ponds. Algal-specific PLFAs were absent at three of the four sites
      investigated, and delta(13)CPLFA values were generally within ~30/00 of that
      reported for oil sands bitumen (~-300/00), suggesting that the microbial
      communities growing on petroleum constituents were dominated by aerobic
      heterotrophs. Delta(14)CPLFA values ranged from -906 to -5860/00 and pointed to
      significant uptake of fossil carbon, particularly in PLFAs (e.g., cy17:0 and
      cy19:0) often associated with petroleum hydrocarbon degrading bacteria. The
      comparatively heavier Delta(14)C values found in other, less specific PLFAs
      (e.g., 16:0) indicated the preferential uptake of younger organic matter by the
      general microbial population. Since the main carbon pools in tailings sediment
      were essentially "radiocarbon dead" (i.e., Delta(14)C ~ -10000/00), the principal
      source for this relatively modern carbon is considered to be the Athabasca River,
      which provides the bulk of the water used in the bitumen extraction process. The
      preferential utilization of the minor amount of younger and presumably more
      labile material present in systems otherwise dominated by petroleum carbon has
      important implications for remediation strategies, since it implies that organic
      contaminants may persist long after reclamation has begun. Alternatively, this
      young organic matter could play a vital and necessary role in supporting the
      microbial utilization of fossil carbon via cometabolism or priming processes.

PMID- 23957579
TI  - Comparative studies of structural, thermal, optical, and electrochemical
      properties of azines with different end groups with their azomethine analogues
      toward application in (opto)electronics.
AB  - Two series of azines and their azomethine analogues were prepared via
      condensation reaction of benzaldehyde, 2-hydroxybenzaldehyde, 4
      pyridinecarboxaldehyde, 2-thiophenecarboxaldehyde, and 4
      (diphenylamino)benzaldehyde with hydrazine monohydrate and 1,4-phenylenediamine,
      respectively. The structures of given compounds were characterized by FTIR, (1)H
      NMR, and (13)C NMR spectroscopy as well as elemental analysis. Optical,
      electrochemical, and thermal properties of all compounds were investigated by
      means of differential scanning calorimetry (DSC), UV-vis spectroscopy, stationary
      and time-resolved photoluminescence spectroscopy, and cycling voltammetry (CV).
      Additionally, the electronic properties, that is, orbital energies and resulting
      energy gap were calculated theoretically by density functional theory (DFT).
      Influence of chemical structure of the compounds on their properties was
      analyzed. 

PMID- 23957580
TI  - Multivessel coronary revascularization and outcomes in kidney transplant
      recipients.
AB  - Coronary artery disease is a major cause of morbidity and mortality in the kidney
      transplant population. We compared the long-term outcomes of coronary artery
      bypass graft (CABG) surgery with percutaneous coronary intervention (PCI) for
      multivessel coronary disease in a contemporary cohort of US kidney transplant
      recipients. From the U.S. Renal Data System, we identified all adult kidney
      transplant patients with >=6 months of Medicare A+B undergoing first recorded
      multivessel coronary revascularization from 1997 to 2009. The associations of
      CABG versus PCI with death and the composite of death or myocardial infarction
      (MI) were compared using proportional hazards regression. Of the 2272 patients
      included in the study, 1594 underwent CABG and 678 underwent PCI. The estimated 5
      year survival rate was 55% [95% confidence interval (CI) 53% to 57%] following
      coronary revascularization, with no significant association between
      revascularization type and death [adjusted hazard ratio (aHR) = 1.08; CI 0.94
      1.23] or the composite of death or MI (aHR = 1.07; CI 0.96-1.18). Separate
      propensity score-matched analyses yielded similar results. In this analysis of
      kidney transplant recipients undergoing multivessel coronary revascularization,
      we found no difference between CABG and PCI in terms of survival or the composite
      of death and MI.

PMID- 23957581
TI  - Transmastoid repair of meningoencephalic herniation associated with cholesteatoma
      by canal wall-down procedure: our experience in eighteen patients.

PMID- 23957582
TI  - Drug-induced seizures in children and adolescents presenting for emergency care:
      current and emerging trends.
AB  - CONTEXT: Seizures may be the presenting manifestation of acute poisoning in
      children. Knowledge of the etiologic agent, or likely drug-class exposure, is
      crucial to minimize morbidity and optimize care. OBJECTIVES: To describe the
      agents most commonly responsible for pediatric drug-induced seizures, whose
      evaluation included a medical toxicology consultation in the United States.
      METHODS: Using the 37 participating sites of the Toxicology Investigators
      Consortium (ToxIC) Case Registry, a cross-country surveillance tool, we conducted
      an observational study of a prospectively collected cohort. We identified all
      pediatric (younger than 18 years) reports originating from an Emergency
      Department (ED) which included a chemical or drug-induced seizure, and required a
      medical toxicology consultation between April 1, 2010 and March 31, 2012.
      Results. We identified 142 pediatric drug-induced seizure cases (56% male), which
      represent nearly 5% of pediatric cases requiring bedside consultation by medical
      toxicologists. One-hundred and seven cases (75%) occurred in children aged 13-18
      years, and 86 (61%) resulted from intentional ingestions. Antidepressants were
      the most commonly identified agents ingested (n = 61; 42%), of which bupropion
      was the leading drug (n = 30; 50% of antidepressants), followed by
      anticholinergics/antihistamines (n = 31; 22%). All antidepressant-induced
      seizures in teenagers were intentional and represented self-harm behavior.
      Sympathomimetic agents, including street drugs, represent the most common agents
      in children younger than 2 years (n = 4/19). CONCLUSION: Antidepressants, and
      specifically bupropion, are presently the most common medications responsible for
      pediatric drug-induced seizures requiring medical toxicology consultation in the
      United States. In teenagers presenting with new-onset seizures of unknown
      etiology, the possibility of deliberate self-poisoning should be explored, since
      most drug-induced seizures in this age group resulted from intentional ingestion.

PMID- 23957583
TI  - Evaluation of a porcine vascular model to assess the efficacy of various
      hemostatic techniques.
AB  - BACKGROUND: A novel live porcine model replicated the endoscopic surgical field
      of a carotid arterial injury of the human skull base. Hemostatic techniques were
      applied to jugular venous and carotid arterial injuries, including muscle
      patches, hemoclips, and aneurysm clips. Doppler imaging distal to the injury
      assessed flow through the repaired vessel. MATERIALS AND METHODS: External
      jugular veins, and internal carotid arteries isolated from seven live
      anesthetized 100 kg pigs, were placed into a sinus model otorhino neuro trainer
      for visualization via an endoscopic nasal approach. Vessels were systematically
      injured and repaired, and Doppler measurements were made to assess flow through
      the vessels before injury and following repair. RESULTS AND CONCLUSIONS: Blood
      pressures were maintained within physiological ranges, despite blood losses of up
      to 4.5 l. Venous injuries were repaired using Floseal, hemoclips, and aneurysm
      clips, while arterial injuries were repaired with muscle patches and aneurysm
      clips. Blood flow remained in all vessels after repair. This porcine model was
      effective for demonstration of arterial and venous injuries during endoscopic
      skull base surgery. Crushed muscle patch was effective for arterial injuries of 3
      mm, and the aneurysm clips for injuries of 5 mm. Jugular venous injuries of 3 mm
      were repaired using Floseal, 5 mm using hemoclips, and 6 mm using aneurysm clips.
      Doppler imaging was a noninvasive means of demonstrating ongoing flow through
      injured and repaired vessels. The model represents a valuable training tool with
      the potential to train endoscopic skull base teams the skills required to manage
      an internal carotid artery injury.

PMID- 23957584
TI  - Evolution of pyruvate kinase-deficient Escherichia coli mutants enables glycerol
      based cell growth and succinate production.
AB  - AIMS: The aim of this study was to engineer Escherichia coli strains that
      efficiently produce succinate from glycerol under anaerobic conditions after an
      aerobic growth phase. METHODS AND RESULTS: We constructed E. coli strain ss195
      with deletions of pykA and pykF, which resulted in slow growth on glycerol as
      sole carbon source. This growth defect was overcome by the selection of fast
      growing mutants. Whole-genome resequencing of the evolved mutant ss251 identified
      the mutation A595S in PEP carboxylase (Ppc). Reverse metabolic engineering by
      introducing the wild-type allele revealed that this mutation is crucial for the
      described phenotype. Strain ss251 and derivatives thereof produced succinate with
      high yields above 80% mol mol(-1) from glycerol under nongrowth conditions.
      CONCLUSIONS: The results show that during the aerobic growth of ss251, the
      formation of pyruvate proceeds via the proposed POMP pathway, starting with the
      carboxylation of PEP by Ppc. The resulting oxaloacetate is reduced by malate
      dehydrogenase (Mdh) to malate, which is then decarboxylated back to pyruvate by a
      malic enzyme (MaeA or MaeB). Mutation of ppc is crucial for fast growth of pykAF
      mutants on glycerol. SIGNIFICANCE AND IMPACT OF STUDY: An E. coli mutant that is
      capable of achieving high yields of succinate (a top valued-added chemical) from
      glycerol (an abundant carbon source) was constructed. The identified ppc mutation
      could be applied to other production strains that require strong PEP
      carboxylation fluxes.

PMID- 23957585
TI  - Fabrication of contrast agents for magnetic resonance imaging from polymer-brush
      afforded iron oxide magnetic nanoparticles prepared by surface-initiated living
      radical polymerization.
AB  - The aim of this study is to fabricate a contrast agent for magnetic resonance
      imaging (MRI) by using hybrid particles composed of a core of iron oxide
      magnetite (Fe3O4) nanoparticles and a shell of hydrophilic polymer brush
      synthesized by surface-initiated (SI) living radical polymerization. To achieve
      this, Fe3O4 nanoparticles were surface-modified with initiating groups for atom
      transfer radical polymerization (ATRP) via a ligand-exchange reaction in the
      presence of a triethoxysilane derivative having an ATRP initiation site. The ATRP
      initiator-functionalized Fe3O4 nanoparticles were used for performing the SI-ATRP
      of methyl methacrylate to demonstrate the ability of the synthesized
      nanoparticles to produce well-defined polymer brushes on their surfaces. The
      polymerization proceeded in a living fashion so as to produce graft polymers with
      targeted molecular weights and narrow molecular weight distribution. The average
      graft density was estimated to be as high as 0.7 chains/nm(2), which indicates
      the formation of so-called concentrated polymer brushes on the Fe3O4
      nanoparticles. Dynamic light scattering and transmission electron microscope
      observations of the hybrid nanoparticles revealed their uniformity and
      dispersibility in solvents to be excellent. A similar polymerization process was
      conducted using a hydrophilic monomer, poly(ethylene glycol) methyl ether
      methacrylate (PEGMA), to prepare Fe3O4 nanoparticles grafted with poly(PEGMA)
      brushes. The resultant hybrid nanoparticles showed excellent dispersibility in
      aqueous media including physiological conditions without causing any
      aggregations. The blood clearance and biodistribution of the hybrid particles
      were investigated by intravenously injecting particles labeled with a radio
      isotope, (125)I, into mice. It was found that some hybrid particles exhibited an
      excellently prolonged circulation lifetime in the blood with a half-life of about
      24 h. When such hybrid particles were injected intravenously into a tumor-bearing
      mouse, they preferentially accumulated in the tumor tissues owing to the so
      called enhanced permeability and retention effect. The tumor-targeted delivery
      was visualized by a T2-enhaced MRI measurement. 

PMID- 23957587
TI  - The potential role of CD16+ Vgamma2Vdelta2 T cell-mediated antibody-dependent
      cell-mediated cytotoxicity in control of HIV type 1 disease.
AB  - Increasing evidence has suggested that HIV infection severely damages the
      Vgamma2Vdelta2 (Vdelta2) T cells that play an important role in the first-line
      host response to infectious disease. However, little is known about Vdelta2 T
      cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) in HIV
      disease. We found that although the CD16(+) Vdelta2 T cell subset hardly
      participated in phosphoantigen responses dominated by the CD16(-) Vdelta2 T cell
      subset, the potency of the ADCC function of Vdelta2 T cells was correlated with
      the frequency of the CD16(+) subset. Thus, two distinct and complementary Vdelta2
      T cell subsets discriminated by CD16 were characterized to explore the respective
      impacts of HIV-1 infection on them. HIV-1 disease progression was not only
      associated with the phosphoantigen responsiveness of the CD16(-) Vdelta2 subset,
      but also with the ability of the CD16(+) Vdelta2 subset to kill antibody-coated
      target cells. Furthermore, both of the two Vdelta2 functional subsets could be
      partially restored in HIV-infected patients with antiretroviral therapy. Notably,
      in the context of an overall HIV-mediated Vdelta2 T cell depletion, despite the
      decline of phosphoantigen-responsive CD16(-) Vdelta2 cells, CD16(+) Vdelta2 cell
      mediated ADCC was not compromised but exhibited a functional switch with dramatic
      promotion of degranulation in the early phase of HIV infection and chronic
      infection with slower disease progression. Our study reveals functional
      characterizations of the two Vdelta2 T cell subsets with different activation
      pathways during HIV-1 infection and provides a rational direction for activating
      the CD16(+) Vdelta2 T cells capable of mediating ADCC as a means to control HIV-1
      disease.

PMID- 23957589
TI  - FliS modulates FlgM activity by acting as a non-canonical chaperone to control
      late flagellar gene expression, motility and biofilm formation in Yersinia
      pseudotuberculosis.
AB  - The FlgM-FliA regulatory circuit plays a central role in coordinating bacterial
      flagellar assembly. In this study, we identified multiple novel binding partners
      of FlgM using bacterial two-hybrid screening. Among these binding partners, FliS,
      the secretion chaperone of the filament protein FliC, was identified to compete
      with FliA for the binding of FlgM. We further showed that by binding to FlgM,
      FliS protects it from secretion and degradation, thus maintaining an
      intracellular pool of FlgM reserved as the FliS-FlgM complex. Consequently, we
      found that the flagellar late-class promoter activities are significantly
      increased in the fliS deletion mutant. The fliS mutant is weakly motile and shows
      significantly increased biofilm formation on biotic surface. Based on the results
      obtained, we established for the first time the regulatory role of the flagellin
      chaperone FliS to fine-tune late flagellar assembly by modulating FlgM activity. 

PMID- 23957588
TI  - Identifying potential RNAi targets in grain aphid (Sitobion avenae F.) based on
      transcriptome profiling of its alimentary canal after feeding on wheat plants.
AB  - BACKGROUND: The grain aphid (Sitobion avenae F.) is a major agricultural pest
      which causes significant yield losses of wheat in China, Europe and North America
      annually. Transcriptome profiling of the grain aphid alimentary canal after
      feeding on wheat plants could provide comprehensive gene expression information
      involved in feeding, ingestion and digestion. Furthermore, selection of aphid
      specific RNAi target genes would be essential for utilizing a plant-mediated RNAi
      strategy to control aphids via a non-toxic mode of action. However, due to the
      tiny size of the alimentary canal and lack of genomic information on grain aphid
      as a whole, selection of the RNAi targets is a challenging task that as far as we
      are aware, has never been documented previously. RESULTS: In this study, we
      performed de novo transcriptome assembly and gene expression analyses of the
      alimentary canals of grain aphids before and after feeding on wheat plants using
      Illumina RNA sequencing. The transcriptome profiling generated 30,427 unigenes
      with an average length of 664 bp. Furthermore, comparison of the transcriptomes
      of alimentary canals of pre- and post feeding grain aphids indicated that 5490
      unigenes were differentially expressed, among which, diverse genes and/or
      pathways were identified and annotated. Based on the RPKM values of these
      unigenes, 16 of them that were significantly up or down-regulated upon feeding
      were selected for dsRNA artificial feeding assay. Of these, 5 unigenes led to
      higher mortality and developmental stunting in an artificial feeding assay due to
      the down-regulation of the target gene expression. Finally, by adding
      fluorescently labelled dsRNA into the artificial diet, the spread of fluorescence
      signal in the whole body tissues of grain aphid was observed. CONCLUSIONS:
      Comparison of the transcriptome profiles of the alimentary canals of pre- and
      post-feeding grain aphids on wheat plants provided comprehensive gene expression
      information that could facilitate our understanding of the molecular mechanisms
      underlying feeding, ingestion and digestion. Furthermore, five novel and
      effective potential RNAi target genes were identified in grain aphid for the
      first time. This finding would provide a fundamental basis for aphid control in
      wheat through plant mediated RNAi strategy.

PMID- 23957590
TI  - Long-term treatment with probiotics in primary care patients with irritable bowel
      syndrome--a randomised, double-blind, placebo controlled trial.
AB  - OBJECTIVE. Meta-analyses have indicated effect of probiotics on irritable bowel
      syndrome (IBS). However, few long-term trials have been conducted and uncertainty
      remains as to effectiveness and long-term effect in a primary care setting. We
      aimed to investigate the effect of probiotics compared with placebo in the
      management of IBS in primary care during a 6-month treatment period and with a 6
      month follow-up. MATERIAL AND METHODS. We randomized IBS patients fulfilling Rome
      III criteria to receive two capsules twice daily either containing placebo or a
      probiotic mixture of Lactobacillus paracasei ssp paracasei F19, Lactobacillus
      acidophilus La5 and Bifidobacterium Bb12 in an amount of 1.3 * 10(10) CFU per
      capsule. Primary endpoint was proportion of responders defined as patients
      reporting adequate relief (AR) at least 50% of the time in the 6-month treatment
      period. Secondary outcomes were proportions of patients reporting AR at different
      time points, and change in gastrointestinal symptoms and health-related quality
      of life (HrQOL) from baseline to 6 and 12 months. RESULTS. A total of 131
      patients were included in this study. The proportion of responders in the
      treatment period was 52% (35/67) in the probiotic group versus 41% (26/64) in the
      placebo group, p = 0.18. Overall we found no difference between the groups in
      change in gastrointestinal symptoms after treatment. Patients improved in HrQOL,
      but with no statistically significant difference between the groups. CONCLUSION.
      During a 6-month treatment period, we were not able to detect a positive effect
      of probiotic when compared with placebo.

PMID- 23957591
TI  - Numerical investigation of root canal irrigation adopting innovative needles with
      dimple and protrusion.
AB  - As important passive flow control methods, dimples and protrusions have been
      successfully implemented via geometric modifications to manipulate flow fields to
      get a desired flow parameters enhancement. In this research, two novel needles
      were proposed based on a prototype by means of the dimple and protrusion, and
      flow patterns within a root canal during final irrigation with these needles were
      numerically investigated. The calculation cases consistent with the clinically
      realistic irrigant flow rates, which are 0.02, 0.16 and 0.26 mL s(-1) are marked
      as case A, B and C, respectively. The characteristic parameters to estimate
      irrigation efficiency, such as shearing effect, mean apical pressure, irrigation
      replacement and fluid agitation, were compared and the optimal geometry in every
      calculation case was obtained. As shown from the results, flow rates and needle
      geometries were the causes of irrigation parameters variations. The sum of shear
      stress, irrigation replacement and fluid agitation were equal in the low flow
      rate case A, however, the needle with a protrusion on its tip had advantages in
      the three irrigation characteristic parameters above in calculation case B, and
      the needle with a dimple on its tip had advantages in calculation case C.
      Furthermore, the needles proposed did not give rise to the risk of irrigant
      extrusion. These needles can be better choices at larger flow rates. Therefore,
      needle geometry optimizations utilizing passive flow control methods are worthy
      to be investigated in the root canal irrigation enhancement.

PMID- 23957592
TI  - Using joint utilities of the times to response and toxicity to adaptively
      optimize schedule-dose regimes.
AB  - A Bayesian two-stage phase I-II design is proposed for optimizing administration
      schedule and dose of an experimental agent based on the times to response and
      toxicity in the case where schedules are non-nested and qualitatively different.
      Sequentially adaptive decisions are based on the joint utility of the two event
      times. A utility function is constructed by partitioning the two-dimensional
      positive real quadrant of possible event time pairs into rectangles, eliciting a
      numerical utility for each rectangle, and fitting a smooth parametric function to
      the elicited values. We assume that each event time follows a gamma distribution
      with shape and scale parameters both modeled as functions of schedule and dose. A
      copula is assumed to obtain a bivariate distribution. To ensure an ethical trial,
      adaptive safety and efficacy acceptability conditions are imposed on the
      (schedule, dose) regimes. In stage 1 of the design, patients are randomized
      fairly among schedules and, within each schedule, a dose is chosen using a hybrid
      algorithm that either maximizes posterior mean utility or randomizes among
      acceptable doses. In stage 2, fair randomization among schedules is replaced by
      the hybrid algorithm. A modified version of this algorithm is used for nested
      schedules. Extensions of the model and utility function to accommodate death or
      discontinuation of follow up are described. The method is illustrated by an
      autologous stem cell transplantation trial in multiple myeloma, including a
      simulation study. 

PMID- 23957593
TI  - On the cross-cultural replicability of the resilient, undercontrolled, and
      overcontrolled personality types.
AB  - Personality types reflect typical configurations of personality attributes within
      individuals. Over the last 20 years, researchers have identified a set of three
      replicable personality types: resilient (R), undercontrolled (U), and
      overcontrolled (O) types. In this study, we examined the cross-cultural
      replicability of the RUO types in Italy, Poland, Spain, and the United States.
      Personality types were identified using cluster analyses of Big Five profiles in
      large samples of college students from Italy (n = 322), the United States (n =
      499), Spain (n = 420), and Poland (n = 235). Prior to clustering the profiles,
      the measurement invariance of the Big Five measure across samples was tested. We
      found evidence for the RUO types in all four samples. The three-cluster solution
      showed a better fit over alternative solutions and had a relatively high degree
      of cross-cultural generalizability. The RUO types are evident in samples from
      four countries with distinct linguistic and cultural traditions. Results were
      discussed in light of the importance of considering how traits are organized
      within individuals for advancing contemporary personality psychology. 

PMID- 23957594
TI  - Reduced lung dose and improved inspiration level reproducibility in visually
      guided DIBH compared to audio coached EIG radiotherapy for breast cancer
      patients.
AB  - INTRODUCTION: Patients with left-sided breast cancer with lymph node involvement
      have routinely been treated with enhanced inspiration gating (EIG) for a decade
      at our institution. In a transition from EIG to deep inspiration breath hold
      (DIBH) we compared the two techniques with focus on target coverage, dose to
      organs at risk and reproducibility of the inspiration level (IL). MATERIAL AND
      METHODS: Twenty-four patients were computed tomography (CT) scanned with EIG and
      DIBH. For DIBH we used visual feedback and for EIG audio coaching, both during
      scan and treatment. Treatment plans for 50 Gy over 25 fractions were calculated.
      Seventeen of the patients were included in the analysis of reproducibility. They
      were audio coached for one minute before beam-on in DIBH at nine treatment
      sessions. These respiration curves were analysed with average maximum IL and
      standard deviation (SD) for the EIG part of the respiratory signal, and mean IL
      and SD for the DIBH. Comparison of dosimetric and respiration parameters were
      performed with the Wilcoxon signed rank-sum test. RESULTS: In DIBH, the
      ipsilateral lung volume increased further compared to EIG (p < 0.0004, mean
      increase 11%). This lead to a 9% mean reduction (p = 0.002) of the ipsilateral
      lung volume receiving 20 Gy (V20 Gy). We found no other significant dosimetric
      differences between the two methods. The reproducibility of the IL was better
      with the DIBH method, observed as a significantly smaller SD in most patients (p
      < 0.04 for 16 of 17 patients). CONCLUSION: The DIBH method resulted in a
      significantly larger lung volume and lower ipsilateral lung V20 Gy compared to
      EIG. The IL for visually guided DIBH was more reproducible than audio-coached
      EIG. Based on these findings, the DIBH technique is our new breathing adaptation
      standard for radiotherapy of patients with left-sided breast cancer with lymph
      node involvement.

PMID- 23957595
TI  - Can dogs smell lung cancer? First study using exhaled breath and urine screening
      in unselected patients with suspected lung cancer.
AB  - BACKGROUND: On the basis of our own experience and literature search, we
      hypothesised that a canine olfactory test may be useful for detecting lung cancer
      in an unselected population of patients suspected to have lung cancer. MATERIAL
      AND METHODS: We conducted a prospective study of 93 patients consecutively
      admitted to hospital with suspected lung cancer. Exhaled breath and urine were
      sampled before the patients underwent bronchoscopy. The canine olfactory test was
      performed in a double-blinded manner. Sensitivity and specificity were outcome
      measures. RESULTS: With 99% sensitivity, the olfactory test demonstrated that
      dogs have the ability to distinguish cancer patients from healthy individuals.
      With an intensified training procedure, the exhaled breath and urine tests showed
      sensitivity rates of 56-76% and specificity rates of 8.3-33.3%, respectively, in
      our heterogeneous study population. CONCLUSION: Although the olfactory test
      appears to be a promising tool for the detection of cancer, the main challenge is
      to determine whether the test can sufficiently discriminate between patients at
      risk, patients with benign disease, and patients with malignant disease. We need
      to gain a deeper understanding of this test and further refine it before applying
      it as a screening tool for lung cancer in clinical settings.

PMID- 23957596
TI  - Changes in preoperative characteristics in patients undergoing radical
      prostatectomy--a 16-year nationwide analysis.
AB  - BACKGROUND: The Danish attitude for diagnosis and treatment of early localized
      prostate cancer (PCa) has historically been conservative. Denmark introduced
      radical prostatectomy (RP) as the last of the Nordic countries in 1995. However,
      a rapid increment in the Danish incidence of PCa is indicative of a shift in
      attitude with increasing opportunistic PSA testing. This had led to an increasing
      number of RPs being performed in Denmark. The objective of this study was to
      analyze changes in preoperative characteristics over time for the complete cohort
      of 6489 men who underwent RP between 1995 and 2011. Our hypothesis was that an
      increasing amount of men undergo RP for lower risk PCa. MATERIAL AND METHODS: All
      patients operated from 1995 to 2011 were identified via patient files and
      registries. Changes over time in age at surgery, preoperative PSA, clinical T
      category, biopsy Gleason score (GS), and D'Amico classification are described.
      Tests for statistically significant changes were performed. RESULTS: Median age
      increased from 61.4 to 64.8 years (p < 0.0001) during the 16-year period. Median
      PSA declined from 11.5 to 7.9 ng/ml (p < 0.0001). Distribution of biopsy GS
      changed significantly, especially after 2005. Biopsy GS = 7 was found in 20.2% of
      the patients in 2005 compared to 57.1% in 2011. The proportion of T1 disease
      increased from 32% to 56%. Significant changes in percentage of patients
      according to the D'Amico classification were found. After 2005 the proportion of
      intermediate-risk patients increased significantly. The proportion of patients
      age 70 or above increased from 2% to 13% in the period studies. CONCLUSION:
      Significant preoperative stage- and Gleason grade migration was found in this
      complete Danish nationwide cohort of patients undergoing RP during the past 16
      years. This effect is most likely attributed to an increasing use of PSA as
      marker for early prostate cancer diagnosis in Denmark and new international
      guidelines for Gleason grading and scoring.

PMID- 23957597
TI  - Neural basis of anhedonia as a failure to predict pleasantness in schizophrenia.
AB  - OBJECTIVES: Anhedonia in schizophrenia results from a deficit in anticipatory
      pleasure rather than consummatory pleasure. This study aimed to determine the
      neural basis of the predictive and experiential components of anticipatory
      pleasure in schizophrenia. METHODS: A hedonic rating task was performed by 15
      patients with schizophrenia and 17 controls while undergoing functional magnetic
      resonance imaging. Participants evaluated the level of pleasantness for the
      preview/predictive phase, comprising a narration and adjunctive audiovisual
      stimuli for pleasurable experience, and the subsequent viewing/experiential
      phase, comprising a video clip for a pleasant event. RESULTS: A significant group
      by-phase interaction was seen in the rostral anterior cingulate cortex (ACC) and
      caudate, resulting from reduced activations in patients during the preview phase.
      Patients showed significantly reduced activation in the frontopolar cortex and
      rostral ACC during the preview phase. The signal changes in the caudate and
      frontopolar cortex were associated with increase in hedonic response during the
      sequential pleasure experiences. CONCLUSIONS: Augmentation of hedonic enjoyment
      between the predictive and experiential stages of anticipatory pleasure is
      reduced in schizophrenia because of diminished activity in the reward-related
      regions during the prediction of pleasure. During cued-emotional experiences of
      anticipatory pleasure, patients seem to have difficulties in the integration of
      emotional information.

PMID- 23957598
TI  - Vitiligo: an unusual finding in Cronkhite-Canada syndrome.

PMID- 23957599
TI  - Adherence to oxygenation and ventilation targets in mechanically ventilated
      premature and sick newborns: a retrospective study.
AB  - BACKGROUND: Ventilator treatment exposes newborns to both hyperoxemia and
      hyperventilation. It is not known how common hyperoxemia and hyperventilation are
      in neonatal intensive care units in Norway. The purpose of this study was to
      assess the quality of current care by studying deviations from the target range
      of charted oxygenation and ventilation parameters in newborns receiving
      mechanical ventilation. METHODS: Single centre, retrospective chart review that
      focused on oxygen and ventilator treatment practices. RESULTS: The bedside
      intensive care charts of 138 newborns reflected 4978 hours of ventilator time.
      Arterial blood gases were charted in 1170 samples. In oxygen-supplemented
      newborns, high arterial pressure of oxygen (PaO2) values were observed in 87/609
      (14%) samples. In extremely premature newborns only 5% of the recorded PaO2
      values were high. Low arterial pressure of CO2 (PaCO2) values were recorded in
      187/1170 (16%) samples, and 64 (34%) of these were < 4 kPa. Half of all low
      values were measured in extremely premature newborns. Tidal volumes above the
      target range were noted in 22% of premature and 20% of full-term newborns.
      CONCLUSIONS: There was a low prevalence of high PaO2 values in premature
      newborns, which increased significantly with gestational age (GA). The prevalence
      of low PaCO2 values was highest among extremely premature newborns and decreased
      with increasing GA. Further studies are needed to identify whether adherence to
      oxygenation and ventilation targets can be improved by clearer communication and
      allocation of responsibilities between nurses and physicians.

PMID- 23957601
TI  - Nanoparticles for catalysis.

PMID- 23957600
TI  - The physics of broadcast spawning in benthic invertebrates.
AB  - Most benthic invertebrates broadcast their gametes into the sea, whereupon
      successful fertilization relies on the complex interaction between the physics of
      the surrounding fluid flow and the biological properties and behavior of eggs and
      sperm. We present a holistic overview of the impact of instantaneous flow
      processes on fertilization across a range of scales. At large scales, transport
      and stirring by the flow control the distribution of gametes. Although mean
      dilution of gametes by turbulence is deleterious to fertilization, a variety of
      instantaneous flow phenomena can aggregate gametes before dilution occurs. We
      argue that these instantaneous flow processes are key to fertilization
      efficiency. At small scales, sperm motility and taxis enhance contact rates
      between sperm and chemoattractant-releasing eggs. We argue that sperm motility is
      a biological adaptation that replaces molecular diffusion in conventional mixing
      processes and enables gametes to bridge the gap that remains after aggregation by
      the flow. 

PMID- 23957602
TI  - Fluorescein analogue xanthene-9-carboxylic acid: a transition-metal-free CO
      releasing molecule activated by green light.
AB  - 6-Hydroxy-3-oxo-3H-xanthene-9-carboxylic acid is introduced as the first
      transition-metal-free carbon monoxide releasing molecule activated by visible
      light (photoCORM). This water-soluble fluorescein analogue releases carbon
      monoxide in both water and methanol upon irradiation at 500 nm. When selectively
      irradiated in the presence of hemoglobin (Hb) under physiological conditions,
      released CO is quantitatively trapped to form carboxyhemoglobin (COHb). The
      reaction progress can be accurately monitored by characteristic absorption and
      emission properties of the reactants and products. 

PMID- 23957603
TI  - The effects of probiotics on barrier function and mucosal pouch microbiota during
      maintenance treatment for severe pouchitis in patients with ulcerative colitis.
AB  - BACKGROUND: A total of 10-15% of patients with an ileoanal pouch develop severe
      pouchitis necessitating long-term use of antibiotics or pouch excision.
      Probiotics reduce the risk of recurrence of pouchitis, but mechanisms behind
      these effects are not fully understood. AIM: To examine mucosal barrier function
      in pouchitis, before and after probiotic supplementation and to assess
      composition of mucosal pouch microbiota. METHODS: Sixteen patients with severe
      pouchitis underwent endoscopy with biopsies of the pouch on three occasions:
      during active pouchitis; clinical remission by 4 weeks of antibiotics; after 8
      weeks of subsequent probiotic supplementation (Ecologic 825, Winclove, Amsterdam,
      the Netherlands). Thirteen individuals with a healthy ileoanal pouch were sampled
      once as controls. Ussing chambers were used to assess transmucosal passage of
      Escherichia coli K12, permeability to horseradish peroxidase (HRP) and 51Cr-EDTA.
      Composition and diversity of the microbiota was analysed using Human Intestinal
      Tract Chip. RESULTS: Pouchitis Disease Activity Index (PDAI) was significantly
      improved after antibiotic and probiotic supplementation. Escherichia coli K12
      passage during active pouchitis [3.7 (3.4-8.5); median (IQR)] was significantly
      higher than in controls [1.7 (1.0-2.4); P < 0.01], did not change after
      antibiotic treatment [5.0 (3.3-7.1); P = ns], but was significantly reduced after
      subsequent probiotic supplementation [2.2 (1.7-3.3); P < 0.05]. No significant
      effects of antibiotics or probiotics were observed on composition of mucosal
      pouch microbiota; however, E. coli passage correlated with bacterial diversity (r
      = -0.40; P = 0.018). Microbial groups belonging to Bacteroidetes and Clostridium
      clusters IX, XI and XIVa were associated with healthy pouches. CONCLUSIONS:
      Probiotics restored the mucosal barrier to E. coli and HRP in patients with
      pouchitis, a feasible factor in prevention of recurrence during maintenance
      treatment. Restored barrier function did not translate into significant changes
      in mucosal microbiota composition, but bacterial diversity correlated with
      barrier function.

PMID- 23957604
TI  - Low dose hypersensitivity following in vitro cell irradiation with charged
      particles: Is the mechanism the same as with X-ray radiation?
AB  - PURPOSE: Among the low dose effects that have been discovered during the past
      decade, the low dose hypersensitivity (HRS) is of prime importance. This
      phenomenon, compared to irradiation at higher doses used in conventional
      radiotherapy, enhances cell killing per unit dose at low doses and is followed by
      an induced radioresistance (IRR) effect. On survival fraction curves, a deviation
      from the linear quadratic model can be observed. HRS has mainly been studied
      after irradiation with sparsely ionizing radiation. Little work has been done to
      check its actual existence after irradiation with medium and high linear energy
      transfer (LET) particles. This article reviews recent studies involving HRS
      following irradiation of rodent and human cells with protons, alpha particles and
      carbon ions and assesses the applicability of a photon HRS model to charged
      particles. CONCLUSION: We propose that the HRS threshold dose and the
      radiosensitive parameter alphas may be LET and deoxyribonucleic acid (DNA) damage
      clustering dependent. Combining the use of high-LET particles at low doses and
      chemotherapy strategies increasing the proportion of HRS-sensitive cells could
      become a good candidate treatment for radioresistant cancers.

PMID- 23957605
TI  - Transitional experiences in patients following intracranial aneurysm rupture.
AB  - AIMS AND OBJECTIVES: To describe changes and transitions in everyday life in the
      first two years following an intracranial aneurysm rupture. BACKGROUND: An
      intracranial aneurysm rupture causes a haemorrhagic stroke, and the physical and
      mental consequences of this condition are numerous and complex. In Sweden, some,
      but not all, patients receive rehabilitation for this condition. Patients with
      this type of stroke are not included in the national stroke registry; thus,
      information on the recovery period for these particular patients is lacking.
      DESIGN: A longitudinal mixed methods study design was used. METHODS: The sample
      was consecutive and consisted of 88 patients (84.6% of 104 eligible), acutely
      admitted to a neurosurgical clinic in Stockholm for intracranial aneurysm
      rupture. Data were collected through a postal study-specific questionnaire at 6
      months, 1 year and 2 years postaneurysm rupture. Intramethod mixing was used in
      the data collection, and quantitative and qualitative data were analysed parallel
      with statistical and qualitative content analysis. RESULTS: A majority of
      participants perceived changes in their everyday lives during the first two years
      following aneurysm rupture, and the changes were ongoing with little differences
      reported between 6 months and 2 years after the onset. Internal changes, or
      transitions, were revealed within changes in personality, changed social roles
      and relationships and changed abilities and behaviour. CONCLUSIONS: Recovering
      from an intracranial aneurysm rupture involves a period of intense changes and
      transitions, a vulnerable period for many people that may be made easier to
      manage by the intervention of nurses. RELEVANCE TO CLINICAL PRACTICE: Patients
      experiencing transitions in the recovery period after intracranial aneurysm
      rupture may benefit from nursing interventions that support them through the
      transitional process. Nurse-led follow-up care by a specialist nurse from the
      neurosurgical clinic may be a possible way to provide support.

PMID- 23957606
TI  - Multiwalled carbon nanotube deposition on model environmental surfaces.
AB  - Deposition of multiwalled carbon nanotubes (MWNTs) on model environmental
      surfaces was investigated using a quartz crystal microbalance with dissipation
      monitoring (QCM-D). Deposition behaviors of MWNTs on positively and negatively
      charged surfaces were in good agreement with Derjaguin-Landau-Verwey-Overbeek
      (DLVO) theory, although hydrophobic interactions dominated MWNTs deposition on a
      hydrophobic polystyrene surface. Initial deposition rates (rf) and deposition
      attachment efficiencies (alphaD) depended on solution ionic strengths (IS) and
      surface electrostatic properties. Identical rf and alphaD values at constant IS
      on similar surfaces suggested that deposition was insensitive to surface
      morphology (i.e., bare crystal surface vs coated surface). The dissipation unit
      (D) was used with frequency (f) to investigate nanoparticle deposition:
      |DeltaD/Deltaf| values varied for deposition on different surfaces, indicating
      that the nature of MWNT association with surfaces varied despite constant rf and
      alphaD values. 

PMID- 23957607
TI  - Correlation between particle deformation kinetics and polymer interdiffusion
      kinetics in drying latex films.
AB  - Using an experimental setup which determines the turbidity of the sample and the
      efficiency of Forster resonance energy transfer (FRET) at the same time, we have
      correlated the particle deformation kinetics in a drying latex film, quantified
      by light scattering with the kinetics of polymer interdiffusion. Interdiffusion
      was quantified making use of energy transfer (FRET) between donor molecules and
      acceptor molecules, bound to polymer chains on different particles. When the
      chains cross the interparticle boundaries, the rate of energy transfer increases.
      The latex was prepared by miniemulsion polymerization. The amount of emulsifier
      employed during polymerization had a pronounced effect on the relative timing of
      interdiffusion and particle deformation. Increasing the amount of emulsifier
      delayed the onset of interdiffusion relative to the time when the film became
      transparent. This is mostly the consequence of a size effect, as opposed to
      surfactant acting as a barrier for transport. 

PMID- 23957608
TI  - Theoretical and experimental study of the C-H stretching overtones of
      2,4,6,8,10,12-hexanitro-2,4,6,8,10,12 hexaazaisowurtzitane (CL20).
AB  - An understanding of how molecular environment and structure are reflected in
      optical absorption spectra offers a number of advantages, such as improved
      detection of materials or providing an easy means of distinguishing crystal
      polymorphs of the same molecular solid. This study advances this understanding by
      comparing near IR laser photoacoustic absorption measurements of the first C-H
      stretch overtones around 5975 cm(-1) of beta-2,4,6,8,10,12-hexanitro
      2,4,6,8,10,12-hexaazaisowurtzitane (CL20) to simulated spectra using density
      functional calculations and the local mode model of C-H stretches. The
      calculations reveal that accounting for movement of charge throughout the model
      crystal unit cell with a pure quantum mechanical method in the calculation of the
      transition dipole moment is critical to matching the experimental data.
      Vibrational modes in a given molecule induce movement of charge in neighboring
      molecules, such that calculation of the transition dipole moment had to include
      the entire crystal unit cell. Movement of charge across the periodic boundary
      conditions (PBC) of the model needs to be accounted for to calculate a spectrum
      validated by the experimental measurement. The Hirshfeld population analysis
      minimizes discontinuities for movement of charge across the PBC. 

PMID- 23957609
TI  - Donor-specific anti-HLA antibodies detected by Luminex: predictive for short-term
      but not long-term survival after heart transplantation.
AB  - In heart transplantation, the clinical significance of pretransplant donor
      specific antibodies (DSA) detected by solid phase assay (SPA), which is more
      sensitive than the conventional complement-dependent cytotoxicity (CDC) assays,
      is unclear. The aim was to evaluate SPA performed on pretransplant sera for
      survival after heart transplantation. Pretransplant sera of 272 heart transplant
      recipients were screened for anti-HLA antibodies using CDC and SPA. For
      determination of pretransplant DSA, a single-antigen bead assay was performed.
      The presence of anti-HLA antibodies was correlated with survival. Secondary
      outcome parameters were acute cellular rejection, graft coronary vasculopathy and
      ejection fraction. In Kaplan-Meier analysis, SPA-screening did not predict
      survival (P = 0.494), this in contrast to CDC screening (P = 0.002). However, the
      presence of pretransplant DSA against HLA class I was associated with decreased
      short-term survival compared to non-DSA (P = 0.038). ROC curve analysis showed a
      sensitivity of 76% and specificity of 73% at a cutoff of 2000 MFI. In contrast,
      the presence of anti-HLA antibodies had no influence on long-term survival,
      rejection incidence, and graft function. Thus, detection of DSA class I in
      pretransplant serum is a strong predictor of short-term, but not long-term
      survival and may help in the early management of heart transplant patients.

PMID- 23957610
TI  - In vivo test of a new hands-free tracheostoma inhalation valve, a randomised
      crossover study.

PMID- 23957611
TI  - A preliminary assessment of the impact of hot-melt extrusion on the physico
      mechanical properties of a tablet.
AB  - OBJECTIVES: This research aimed at investigating the difference between the
      powders prior to and after hot melt extrusion. A preliminary assessment was also
      conducted to gain a better mechanistic understanding of the impact of hot melt
      extrusion on tabletability. MATERIALS AND METHODS: Kollidon(r) VA 64 and mannitol
      were sieved into different particles sizes and used as is or after drying for 24
      h. Hot melt extrusion was used to manufacture an amorphous solid dispersion of
      Kollidon(r) VA 64 and mannitol. The extrudates were milled and sieved into
      different particles sizes. Tablets were manufactured from the different powders
      and their tabletability, compressibility and compactibility determined. RESULTS
      AND DISCUSSIONS: It was shown that the as received tablets gave higher
      tabletability compared with the tablets manufactured from the dried or hot melt
      extruded (HME) powder. Differences in the tabletability between the as received.
      dried and HME material could be related back to changes in the bonding area and
      bonding strength as a result of the hot melt extrusion process and/or a loss of
      moisture because of the high processing temperature. CONCLUSIONS: The reduced
      tabletability of the HME tablets appeared to be a function of multiple factors.
      Both the hot melt extrusion process and the moisture content may play significant
      roles in determining this phenomenon.

PMID- 23957612
TI  - Biodegradable polyesters containing ibuprofen and naproxen as pendant groups.
AB  - Controlled release of nonsteroidal anti-inflammatory drugs such as ibuprofen and
      naproxen could be beneficial for the treatment of inflammatory diseases while
      reducing the side effects resulting from their continuous use. Novel
      biodegradable polyesters solely comprised of biocompatible components (e.g.,
      tartaric acid, 1,8-octanediol, and ibuprofen or naproxen as pendant groups) have
      been synthesized using tin(II) 2-ethylhexanoate as catalyst at 130  degrees C and
      subsequently characterized to determine their structures and physicochemical
      properties. The polymers release the free drug (ibuprofen or naproxen) in vitro
      in a controlled manner without burst release, unlike the release rates achieved
      when the drugs are encapsulated in other polymers. These new biomaterials are not
      cytotoxic toward mouse fibroblasts up to 0.10 mg/mL. The drugs retain their
      chemical structure following hydrolytic degradation of the polymer, suggesting
      that bioactivity is preserved. 

PMID- 23957613
TI  - The beneficial effects of levetiracetam on polyneuropathy in the early stage of
      sepsis in rats: electrophysiological and biochemical evidence.
AB  - ABSTRACT Critical illness polyneuropathy (CIP) is a common complication in long
      (>=1 week) critical/intensive care hospitalizations. Rapidly progressing atrophy
      and weakness of the limb, trunk and, particularly, respiratory muscles may lead
      to severe morbidity or mortality. The aim of the present study was to investigate
      the protective effects of levetiracetam (LEV) on CIP in the early stage of sepsis
      in rats. We simulated CIP by a surgically induced sepsis model and verified it by
      lower-limb electromyography (EMG) (amplitude and duration of CMAP, and distal
      latency). We evaluated the effects of various doses of LEV treatment (300, 600,
      and 1200 mg/kg i.p.) on CIP by performing electrophysiology, and determining
      plasma tumor necrosis factor (TNF)-alpha, lipid peroxides (malondialdehyde, MDA)
      levels, and total antioxidant capacity (TAC). Our data showed: (1) significant
      suppression of CMAP amplitude and prolongation of distal latency in the saline
      treated sepsis group, and distal latency as well as CMAP amplitudes benefiting
      best from the 600 mg/kg LEV treatment; (2) significant rise in plasma TNF-alpha
      and MDA levels in the saline-treated sepsis group, but significant ameliorations
      by the 600 and 1200 mg/kg LEV treatment; (3) highly significant suppression of
      TAC in the saline-treated group, but profound reversals in all LEV-treated
      groups. We conclude that 300, 600, and 1200 mg/kg i.p. doses of post-septic
      treatment by LEV has possibly acted in a dose-dependent manner to both protect
      and restore the affected peripheral nerves' axon and myelin following surgical
      disturbance of the cecum to induce sepsis and consequent polyneuropathy.

PMID- 23957614
TI  - Analysis of the global transcriptome of longan (Dimocarpus longan Lour.)
      embryogenic callus using Illumina paired-end sequencing.
AB  - BACKGROUND: Longan is a tropical/subtropical fruit tree of great economic
      importance in Southeast Asia. Progress in understanding molecular mechanisms of
      longan embryogenesis, which is the primary influence on fruit quality and yield,
      is slowed by lack of transcriptomic and genomic information. Illumina second
      generation sequencing, which is suitable for generating enormous numbers of
      transcript sequences that can be used for functional genomic analysis of longan.
      RESULTS: In this study, a longan embryogenic callus (EC) cDNA library was
      sequenced using an Illumina HiSeq 2000 system. A total of 64,876,258 clean reads
      comprising 5.84 Gb of nucleotides were assembled into 68,925 unigenes of 448-bp
      mean length, with unigenes >=1000 bp accounting for 8.26% of the total. Using
      BLASTx, 40,634 unigenes were found to have significant similarity with accessions
      in Nr and Swiss- Prot databases. Of these, 38,845 unigenes were assigned to 43 GO
      sub-categories and 17,118 unigenes were classified into 25 COG sub-groups. In
      addition, 17,306 unigenes mapped to 199 KEGG pathways, with the categories of
      Metabolic pathways, Plant-pathogen interaction, Biosynthesis of secondary
      metabolites, and Genetic information processing being well represented. Analyses
      of unigenes >=1000 bp revealed 328 embryogenesis-related unigenes as well as
      numerous unigenes expressed in EC associated with functions of reproductive
      growth, such as flowering, gametophytogenesis, and fertility, and vegetative
      growth, such as root and shoot growth. Furthermore, 23 unigenes related to
      embryogenesis and reproductive and vegetative growth were validated by
      quantitative real time PCR (qPCR) in samples from different stages of longan
      somatic embryogenesis (SE); their differentially expressions in the various
      embryogenic cultures indicated their possible roles in longan SE. CONCLUSIONS:
      The quantity and variety of expressed EC genes identified in this study is
      sufficient to serve as a global transcriptome dataset for longan EC and to
      provide more molecular resources for longan functional genomics.

PMID- 23957616
TI  - Antineutrophil cytoplasmic antibodies in bile are associated with disease
      activity in primary sclerosing cholangitis.
AB  - OBJECTIVE. Primary sclerosing cholangitis (PSC) is an autoimmune cholestatic
      liver disease of unknown etiology. The role of antineutrophil cytoplasmic
      antibodies (ANCAs) in the serum of patients with PSC remains unclear. We
      hypothesized that ANCA may be detectable in bile, potentially providing
      diagnostic and prognostic information. METHODS. Serum and bile were prospectively
      collected during endoscopic retrograde cholangiography (ERC) in 72 patients with
      PSC and other non-PSC obstructive biliary diseases. ANCA measurements were
      performed by indirect immunofluorescence (IIF). RESULTS. Immunoglobulin G (IgG)
      ANCA was detected significantly more often in the bile of PSC patients (15/39;
      38%) than without (2/33; 6%) (p = 0.001). IgG ANCA in bile was associated with a
      ten times higher risk of PSC (p = 0.005). In addition, IgG ANCA positivity in
      bile was associated with the presence of dominant strictures (p = 0.03),
      cholangiographic severity (p = 0.004), number of ERC (p = 0.01) and interventions
      performed (p = 0.03). However, IgG ANCA in bile did not correlate with
      transplantation, cholangiocarcinoma or death. No association was observed between
      ANCA positivity in sera and ANA and ASCA positivity in sera or bile with the
      above-mentioned clinical features. CONCLUSIONS. The presence of ANCA in the bile
      of patients with PSC is a novel finding and highly suggestive of PSC. Biliary IgG
      ANCA correlates with the severity of bile duct strictures and the ensuing number
      of ERCs and interventions. Therefore, a positive ANCA status in bile may serve as
      a diagnostic and prognostic marker of the disease progression and biliary
      complications.

PMID- 23957617
TI  - Spinal sections and regional variations in the mechanical properties of the
      annulus fibrosus subjected to tensile loading.
AB  - The annulus fibrosus is the primary load-bearing component of the intervertebral
      disc responsible for proper transfer of loads in the spine. The aim of this study
      was to determine selected mechanical parameters of multilayer specimens of the
      annulus fibrosus of the intervertebral disc during uniaxial tensile loading. The
      anatomical location (anterior/posterior) of the test specimens of the annulus
      fibrosus and its location along the length of the spine were analysed to
      determine their impact on the maximum failure force, stiffness, the value of
      Young's modulus and dissipated energy. The results indicated high energy losses
      over the five consecutive precondition loops while the value of the force
      remained at a constant level. The thoracic and lumbar specimens showed the
      highest values of the parameters analysed. There were also significant changes
      depending on the anatomical region of the intervertebral disc, where anterior
      specimens demonstrated higher mechanical values compared to posterior specimens.

PMID- 23957615
TI  - The Legionella pneumophila kai operon is implicated in stress response and
      confers fitness in competitive environments.
AB  - Legionella pneumophila uses aquatic protozoa as replication niche and protection
      from harsh environments. Although L. pneumophila is not known to have a circadian
      clock, it encodes homologues of the KaiBC proteins of Cyanobacteria that regulate
      circadian gene expression. We show that L. pneumophila kaiB, kaiC and the
      downstream gene lpp1114, are transcribed as a unit under the control of the
      stress sigma factor RpoS. KaiC and KaiB of L. pneumophila do not interact as
      evidenced by yeast and bacterial two-hybrid analyses. Fusion of the C-terminal
      residues of cyanobacterial KaiB to Legionella KaiB restores their interaction. In
      contrast, KaiC of L. pneumophila conserved autophosphorylation activity, but KaiB
      does not trigger the dephosphorylation of KaiC like in Cyanobacteria. The crystal
      structure of L. pneumophila KaiB suggests that it is an oxidoreductase-like
      protein with a typical thioredoxin fold. Indeed, mutant analyses revealed that
      the kai operon-encoded proteins increase fitness of L. pneumophila in competitive
      environments, and confer higher resistance to oxidative and sodium stress. The
      phylogenetic analysis indicates that L. pneumophila KaiBC resemble Synechosystis
      KaiC2B2 and not circadian KaiB1C1. Thus, the L. pneumophila Kai proteins do not
      encode a circadian clock, but enhance stress resistance and adaption to changes
      in the environments. 

PMID- 23957618
TI  - Identification of the first nonsense CDSN mutation with expression of a truncated
      protein causing peeling skin syndrome type B.
AB  - BACKGROUND: Peeling skin disease (PSD), a generalized inflammatory form of
      peeling skin syndrome, is caused by autosomal recessive nonsense mutations in the
      corneodesmosin gene (CDSN). OBJECTIVES: To investigate a novel mutation in CDSN.
      METHODS: A 50-year-old white woman showed widespread peeling with erythema and
      elevated serum IgE. DNA sequencing, immunohistochemistry, Western blot and real
      time polymerase chain reaction analyses of skin biopsies were performed in order
      to study the genetics and to characterize the molecular profile of the disease.
      RESULTS: Histology showed hyperkeratosis and acanthosis of the epidermis, and
      inflammatory infiltrates in the dermis. DNA sequencing revealed a homozygous
      mutation leading to a premature termination codon in CDSN: p.Gly142*. Protein
      analyses showed reduced expression of a 16-kDa corneodesmosin mutant in the upper
      epidermal layers, whereas the full-length protein was absent. CONCLUSIONS: These
      results are interesting regarding the genotype-phenotype correlations in diseases
      caused by CDSN mutations. The PSD-causing CDSN mutations identified heretofore
      result in total corneodesmosin loss, suggesting that PSD is due to full
      corneodesmosin deficiency. Here, we show for the first time that a mutant
      corneodesmosin can be stably expressed in some patients with PSD, and that this
      truncated protein is very probably nonfunctional.

PMID- 23957619
TI  - Magnetic resonance imaging of tumor oxygenation and metabolic profile.
AB  - The tumor microenvironment is distinct from normal tissue as a result of abnormal
      vascular network characterized by hypoxia, low pH, high interstitial fluid
      pressure and elevated glycolytic activity. This poses a barrier to treatments
      including radiation therapy and chemotherapy. Imaging methods which can
      characterize such features non-invasively and repeatedly will be of significant
      value in planning treatment as well as monitoring response to treatment. The
      three techniques based on magnetic resonance imaging (MRI) are reviewed here.
      Tumor pO2 can be measured by two MRI methods requiring an exogenous contrast
      agent: electron paramagnetic resonance imaging (EPRI) and Overhauser magnetic
      resonance imaging (OMRI). Tumor metabolic profile can be assessed by a third
      method, hyperpolarized metabolic MR, based on injection of hyperpolarized
      biological molecules labeled with (13)C or (15)N and MR spectroscopic imaging.
      Imaging pO2 in tumors is now a robust pre-clinical imaging modality with
      potential for implementation clinically. Pre-clinical studies and an initial
      clinical study with hyperpolarized metabolic MR have been successful and suggest
      that the method may be part of image-guided radiotherapy to select patients for
      tailored individual treatment regimens.

PMID- 23957620
TI  - Comparing dose-volume histogram and radiobiological endpoints for ranking
      intensity-modulated arc therapy and 3D-radiotherapy treatment plans for locally
      advanced pancreatic cancer.

PMID- 23957621
TI  - Quality assurance of conventional non-CT-based internal mammary lymph node
      irradiation in a prospective Danish Breast Cancer Cooperative Group trial: the
      DBCG-IMN study.
AB  - In 2003, the Danish Breast Cancer Cooperative Group (DBCG) initiated DBCG-IMN, a
      prospective study on the effect of adjuvant internal mammary lymph node
      radiotherapy (IMN-RT) in patients with early lymph node positive breast cancer
      (BC). In the study, standard DBCG IMN-RT was provided only to patients with right
      sided BC. We provide estimates of doses to IMNs and organs at risk (OARs) in
      patients treated with the non-CT-based RT techniques used during the DBCG-IMN
      study. MATERIAL AND METHODS: Five DBCG RT regimens were simulated on planning CT
      scans from 50 consecutively scanned BC patients, 10 in each group. Intended
      target volumes were chest wall or breast and regional lymph nodes +/- IMNs. Field
      planning was conducted in the Eclipse(TM) RT treatment planning system.
      Subsequently, IMN clinical target volumes (CTVs) and OARs were delineated.
      Estimates on doses to the IMN-CTV and OARs were made. RESULTS: IMN dose coverage
      estimates were consistently higher in right-sided techniques where IMN treatment
      was intended (p < 0.0001). Estimated doses to cardiac structures were low
      regardless of whether IMNs were treated or not. Post-lumpectomy patients had the
      highest estimated lung doses. CONCLUSION: Overall, simulator-based treatment
      using the DBCG RT techniques resulted in satisfactory coverage of IMNs and
      acceptable levels of OAR irradiation.

PMID- 23957622
TI  - Characteristics, therapy and outcome in an unselected and prospectively
      registered cohort of patients with gastro-oesophageal cancer.
AB  - PURPOSE: The purpose was to examine characteristics, treatment and outcome in an
      unselected, prospectively registered complete population of patients with gastro
      oesophageal adenocarcinoma cancer (GEA). METHODS: All cases diagnosed with GEA
      between 2008 and 2009 in the Region of Southern Denmark (pop: 1,200,000) were
      registered. Patient characteristics, including performance status, stage and
      therapy, were retrieved from patient charts and used to compare sub-groups of
      patients. RESULTS: Three hundred and thirty patients were registered as having
      GEA. Patients were divided into three clinical subgroups based on initial
      treatment option: group 1: patients with resectable GEA (n = 113); group 2:
      patients receiving first-line therapy (n = 107); group 3: patients receiving no
      tumour-directed therapy (n = 110). Median overall survival (95% CI) in the three
      groups was 36 months (25-not reached), 7.1 months (7-9) and 2.4 months (2-3),
      respectively. Seven percent of patients participated in clinical trials.
      CONCLUSION: Among patients not amendable to resection, around 30% are candidates
      for three-drug combination chemotherapy. Age > 65 years was found not to be a
      poor prognostic factor for survival, giving the possibility of treating elderly
      patients in the future. Many patients (approx. 30%), however, never received
      cancer-directed therapy. In order to improve survival in the entire population,
      it is important that future trials also focus on this group of patients.

PMID- 23957623
TI  - Towards individualized dose constraints: Adjusting the QUANTEC radiation
      pneumonitis model for clinical risk factors.
AB  - BACKGROUND: Understanding the dose-response of the lung in order to minimize the
      risk of radiation pneumonitis (RP) is critical for optimization of lung cancer
      radiotherapy. We propose a method to combine the dose-response relationship for
      RP in the landmark QUANTEC paper with known clinical risk factors, in order to
      enable individual risk prediction. The approach is validated in an independent
      dataset. MATERIAL AND METHODS: The prevalence of risk factors in the patient
      populations underlying the QUANTEC analysis was estimated, and a previously
      published method to adjust dose-response relationships for clinical risk factors
      was employed. Effect size estimates (odds ratios) for risk factors were drawn
      from a recently published meta-analysis. Baseline values for D50 and gamma50 were
      found. The method was tested in an independent dataset (103 patients), comparing
      the predictive power of the dose-only QUANTEC model and the model including risk
      factors. Subdistribution cumulative incidence functions were compared for
      patients with high/low-risk predictions from the two models, and concordance
      indices (c-indices) for the prediction of RP were calculated. RESULTS: The
      reference dose- response relationship for a patient without pulmonary co
      morbidities, caudally located tumor, no history of smoking, < 63 years old, and
      receiving no sequential chemotherapy was estimated as D50(0) = 34.4 Gy (95% CI
      30.7, 38.9), gamma50(0) = 1.19 (95% CI 1.00, 1.43). Individual patient risk
      estimates were calculated. The cumulative incidences of RP in the validation
      dataset were not significantly different in high/low-risk patients when doing
      risk allocation with the QUANTEC model (p = 0.11), but were significantly
      different using the individualized model (p = 0.006). C-indices were
      significantly different between the dose-only and the individualized model.
      CONCLUSION: This study presents a method to combine a published dose-response
      function with known clinical risk factors and demonstrates the increased
      predictive power of the combined model. The method allows for individualization
      of dose constraints and individual patient risk estimates.

PMID- 23957624
TI  - Abdominal visceral and subcutaneous fat increase, insulin resistance and
      hyperlipidemia in testicular cancer patients treated with cisplatin-based
      chemotherapy.
AB  - BACKGROUND: Testicular cancer survivors treated with chemotherapy are at
      increased risk for metabolic syndrome (MetS) and cardiovascular disease (CVD). We
      explored acute effects of chemotherapy by assessing metabolic factors, abdominal
      fat volume, hepatic triglyceride content (HTC) and aortic wall stiffness.
      MATERIAL AND METHODS: We studied 19 testicular cancer patients (age 20-54 years)
      before, at three and nine months after the start of chemotherapy. Blood serum was
      analyzed for lipids, glucose and insulin. Abdominal visceral and subcutaneous fat
      volume and aortic pulse wave velocity were assessed by magnetic resonance imaging
      (MRI) techniques; HTC was measured by proton MR spectroscopy. RESULTS: Three
      months after start of chemotherapy visceral abdominal fat volume had
      significantly increased from 202 +/- 141 to 237 +/- 153 ml (p = 0.009) whereas
      body mass index and subcutaneous fat volume significantly increased nine months
      after treatment from 24.4 +/- 4.0 to 26.4 +/- 4.1 kg/m(2) (p = 0.01) and from 556
      +/- 394 to 668 +/- 460 ml (p = 0.002) respectively. Serum total cholesterol, low
      density lipoprotein cholesterol and insulin also significantly increased three
      months after start of treatment from 4.88 +/- 1.1 to 5.61 +/- 1.50 mmol/l (p =
      0.002), 3.31 +/- 1.16 to 3.73 +/- 1.41 mmol/l (p = 0.02) and 5.7 +/- 4.4 to 9.6
      +/- 6.3 mU/ml (p = 0.03), respectively. Nine months after start of chemotherapy
      serum lipid and insulin concentrations had returned to baseline. HTC increased in
      seven of the 19 patients (36.8%) during follow-up. Aortic pulse wave velocity
      remained unchanged at the three time points measured. CONCLUSION: Cisplatin-based
      chemotherapy was associated with acute insulin resistance, dyslipidemia and an
      immediate increase in abdominal visceral adipose tissue and abdominal
      subcutaneous adipose tissue in testicular cancer patients. A large prospective
      cohort study with long follow-up is warranted to characterize the time course and
      relationship between acutely induced obesity and hypercholesterolemia and the
      development of metabolic syndrome and CVD years later in individual testicular
      cancer survivors.

PMID- 23957625
TI  - One-pot formation of 1,3,4-oxadiazol-2(3H)-ones and dibenzo[c,e]azepines by
      concomitant cathodic reduction of diazonium salts and phenanthrenequinones.
AB  - The one-pot concomitant electrochemical reduction of phenanthrenequinones (1, 2)
      and arenediazonium salts (3a-f) led to the formation of 1,3,4-oxadiazol-2(3H)
      ones (4a-f, 5a) and dibenzo[c,e]azepines (6a-f) when N-methylformamide was used
      as the solvent. A new pathway, different from those previously described with
      other aprotic solvents, is proposed. The experimental data support a radical
      mechanism for the electrochemical process followed by an internal rearrangement
      to give the products. 

PMID- 23957626
TI  - Unilateral rosacea in patients with facial nerve palsy: a mere example of
      immunocompromised district.

PMID- 23957627
TI  - Disclosure experience to partner and its effect on intention to utilize
      prevention of mother to child transmission service among HIV positive pregnant
      women attending antenatal care in Addis Ababa, Ethiopia.
AB  - BACKGROUND: Disclosure of HIV status has become an entry criterion for prevention
      of mother to child transmission programs in resource-constrained countries.
      However, little has been explored about the prevalence of, barriers to, outcomes
      and factors associated with HIV status disclosure among HIV positive pregnant
      women in Ethiopia. METHOD: Cross- sectional study was conducted among 107
      pregnant women who were attending antenatal care in public centers from April to
      June 2011 in Addis Ababa capital city of Ethiopia.Data was collected using
      interviewer administered pretested structured questionnaire and entered and was
      analyzed using SPSS- 15 version. Results presented in tables. RESULT: Seventy
      three percent of women had disclosed their HIV status to their partner.
      Discussion about testing and a smooth relationship with the partner were
      independently associated with their disclosure. Women who disclosed to their
      partners were almost five times more likely to participate in Prevention of
      Mother to Child Transmission programs than their counterparts (AOR = 4.74; 95% CI
      1.24-18.14). CONCLUSIONS: Although most participants disclosed their HIV sero
      positive status, lack of disclosure by some women might result in a limited
      ability to participate in PMTCT programs. Thus, assertiveness and improved
      communication skills training should be offered to HIV positive pregnant mothers
      and be reinforced during on-going counseling.

PMID- 23957628
TI  - Tools for assessing the quality and accessibility of online health information:
      initial testing among breast cancer websites.
AB  - Health websites are used frequently, but there are many concerns about their
      value as information sources. Additionally, there are numerous personal barriers
      that prevent individuals from wholly benefitting from them. In order to assess
      the quality of health websites and their accessibility to users, we created tools
      based on previous research that examine design aspects, information validity,
      motivational health content and literacy content. To test these tools, we
      examined 155 breast cancer websites and created scores for each assessment tool
      to describe the percent of constructs on the average website. Results
      demonstrated that websites performed best on the design tool followed by the
      information validity, motivational health content and literacy assessment tools.
      The average website contained the majority of the design and information validity
      constructs, but only about a third of the motivational health or literacy
      constructs. Multiple items from the motivational health content and literacy
      assessment tools were not found on any of the websites, and many were only
      represented on a handful of sites. Overall, the assessment tools were useful in
      evaluating the quality of websites, and could serve as valuable resources for
      health website developers in the future. 

PMID- 23957629
TI  - "One-pot" reductive lactone alkylation provides a concise asymmetric synthesis of
      chiral isoprenoid targets.
AB  - An efficient method, based on nucleophilic addition to lactones followed by
      modified in situ Clemmensen reduction, provides a short synthetic route to chiral
      isoprenoid targets. The efficacy of this method has been exemplified through the
      synthesis of several targets including the commercial fragrance Rosaphen, the
      side chain of Zaragozic acid C, the cotton leaf sex pheromone, and the side
      chains of vitamin E. 

PMID- 23957630
TI  - Chronic myeloid leukemia: reaching for the cure.

PMID- 23957631
TI  - Synbiotic consumption changes the metabolism and composition of the gut
      microbiota in older people and modifies inflammatory processes: a randomised,
      double-blind, placebo-controlled crossover study.
AB  - BACKGROUND: Ageing can result in major changes in the composition and metabolic
      activities of bacterial populations in the large gut and an impaired immune
      system. AIM: To investigate the effects of synbiotic consumption on the colonic
      microbiota, immune function and health status in older people. METHODS: A
      randomised, double-blind placebo-controlled, 4-week crossover study was carried
      out, involving 43 older volunteers, using a synbiotic comprising the probiotic
      Bifidobacterium longum and an inulin-based prebiotic Synergy 1 (SudZucker,
      Mannheim, Germany). Faecal and blood samples were collected, and clinical status
      scored at the start, and at 2- and 4-week intervals, with a 4-week washout
      between each feeding period. Faecal bacteria were determined by fluorescent in
      situ hybridisation. Short-chain fatty acid concentrations, cytokine production,
      bowel habit and a range of clinical parameters were measured. RESULTS: The
      synbiotic increased bifidobacterial numbers by 1.4 log units (P < 0.0001) and
      also increased members of the phyla Actinobacteria and Firmicutes (P = 0.0004, P
      < 0.0001). Proteobacteria were reduced by 1.0 log units (P < 0.0001). Synbiotic
      feeding was associated with increased butyrate production (P = 0.0399). The pro
      inflammatory response was modified by the synbiotic, with significantly reduced
      pro-inflammatory cytokine TNF-alpha in peripheral blood after 2 and 4 weeks of
      synbiotic consumption (P = 0.02, P = 0.0406). The synbiotic had no effect on
      bowel habit or any clinical parameters. CONCLUSION: Short-term synbiotic use can
      be effective in improving the composition and metabolic activities of colonic
      bacterial communities and immune parameters in older people. This study was
      registered at clinicaltrials.gov as NCT01226212.

PMID- 23957632
TI  - Closing the East-West life expectancy gap in the European union: a new strategy.
AB  - According to recent studies, the difference in life expectancy -the gap-between
      eastern and western countries of the European Union (EU) grows continuously. We
      have analyzed data on life expectancy and household expenditure, corrected by
      price level indices, in the countries of the EU. We have found that eastern
      European countries have less total health expenditure, but expenditures on
      tobacco and alcohol dominate. We propose a new strategy for closing the gap, by
      promoting health care spending, public and private investments in life extension,
      and radical life extension research in the eastern countries of the EU.

PMID- 23957633
TI  - Specificity and transcriptional activity of microbiota associated with low and
      high microbial abundance sponges from the Red Sea.
AB  - Marine sponges are generally classified as high microbial abundance (HMA) and low
      microbial abundance (LMA) species. Here, 16S rRNA amplicon sequencing was applied
      to investigate the diversity, specificity and transcriptional activity of
      microbes associated with an LMA sponge (Stylissa carteri), an HMA sponge
      (Xestospongia testudinaria) and sea water collected from the central Saudi Arabia
      coast of the Red Sea. Altogether, 887 068 denoised sequences were obtained, of
      which 806 661 sequences remained after quality control. This resulted in 1477
      operational taxonomic units (OTUs) that were assigned to 27 microbial phyla. The
      microbial composition of S. carteri was more similar to that of sea water than to
      that of X. testudinaria, which is consistent with the observation that the
      sequence data set of S. carteri contained many more possibly sea water sequences
      (~24%) than the X. testudinaria data set (~6%). The most abundant OTUs were
      shared between all three sources (S. carteri, X. testudinaria, sea water), while
      rare OTUs were unique to any given source. Despite this high degree of overlap,
      each sponge species contained its own specific microbiota. The X. testudinaria
      specific bacterial taxa were similar to those already described for this species.
      A set of S. carteri-specific bacterial taxa related to Proteobacteria and
      Nitrospira was identified, which are likely permanently associated with S.
      carteri. The transcriptional activity of sponge-associated microorganisms
      correlated well with their abundance. Quantitative PCR revealed the presence of
      Poribacteria, representing typical sponge symbionts, in both sponge species and
      in sea water; however, low transcriptional activity in sea water suggested that
      Poribacteria are not active outside the host context.

PMID- 23957634
TI  - Assembly of colloidal silica crystals inside double emulsion drops.
AB  - We investigated the assembly of colloidal silica crystals inside double emulsion
      drops generated in microcapillary microfluidic devices. The double emulsions are
      composed of an aqueous suspension of monodisperse silica particles in the inner
      drop surrounded by a PDMS oil drop that acts as a semipermeable membrane for the
      diffusion of water into or out of the inner drop in the presence of an osmotic
      gradient. Imposing a high osmotic pressure in the continuous phase induces water
      diffusion out of the inner drop, increasing the silica volume fraction
      (phi(silica)) and leading to the formation of a spherical colloidal silica
      crystal. Silica suspensions with no salt or low salt concentration (<10(-3) M)
      formed colloidal crystals with phi(silica) up to 0.68. Monodisperse spherical
      colloidal silica crystals with sizes ranging from 16 to 133 MUm were generated by
      varying the device geometry, flow-rate ratios, and initial silica fraction. At
      salt concentrations > 10(-3) M, the electrostatic repulsion is reduced, and
      crystallization is suppressed. Crystals were preserved in a hydrogel matrix or
      inside a silicone rubber shell. This study demonstrates a robust path for
      controlled colloidal assembly inside double emulsion drops.

PMID- 23957635
TI  - PCR amplification of 4'-thioDNA using 2'-deoxy-4'-thionucleoside 5'
      triphosphates.
AB  - 2'-Deoxy-4'-thioribonucleic acid (4'-thioDNA) having a sulfur atom instead of an
      oxygen atom in the furanose ring has a nuclease resistance and hybridization
      ability higher than that of natural DNA. Despite its great potential for various
      biological applications, a long 4'-thioDNA having all four kinds of 2'-deoxy-4'
      thionucleosides has not been reported. In this study, we describe systematic
      analysis of the incorporation of 2'-deoxy-4'-thionucleoside 5'-triphosphates
      (dSNTPs) using various DNA polymerases. We found that family B DNA polymerases,
      which do not have 3'->5' exonuclease activity, could efficiently incorporate
      dSNTPs via single nucleotide insertion and primer extension. Moreover, 104-mer
      PCR product was obtained even under the conditions in the presence of all four
      kinds of dSNTPs when KOD Dash DNA polymerase was used. The resulting PCR product
      was converted into a natural dsDNA by using PCR with dNTPs, and sequencing of the
      natural dsDNA revealed that the PCR cycle successfully proceeded without losing
      the sequence information of the template. To the best of our knowledge, this is
      the first example of accurate PCR amplification of highly modified DNA in the
      presence of only unnatural dNTPs. 

PMID- 23957636
TI  - Radiofrequency ablation for treatment of auricular keloids: our experience in
      eleven patients.

PMID- 23957637
TI  - Interactions among the early Escherichia coli divisome proteins revealed by
      bimolecular fluorescence complementation.
AB  - We used bimolecular fluorescence complementation (BiFC) assays to detect protein
      protein interactions of all possible pairs of the essential Escherichia coli
      proto-ring components, FtsZ, FtsA and ZipA, as well as the non-essential FtsZ
      associated proteins ZapA and ZapB. We found an unexpected interaction between
      ZipA and ZapB at potential cell division sites, and when co-overproduced, they
      induced long narrow constrictions at division sites that were dependent on FtsZ.
      These assays also uncovered an interaction between ZipA and ZapA that was
      mediated by FtsZ. BiFC with ZapA and ZapB showed that in addition to their
      expected interaction at midcell, they also interact at the cell poles. BiFC
      detected interaction between FtsZ and ZapB at midcell and close to the poles.
      Results from the remaining pairwise combinations confirmed known interactions
      between FtsZ and ZipA, and ZapB with itself. 

PMID- 23957638
TI  - Comparison of two syngeneic orthotopic murine models of pancreatic
      adenocarcinoma.
AB  - BACKGROUND: Pancreatic adenocarcinoma has an extremely poor prognosis. The use of
      appropriate in vivo models is essential in devising methods to improve treatment
      outcomes. METHODS: A pancreatic adenocarcinoma model based on tumor injection
      into the pancreatic head was compared with a pancreatic tail injection model in
      C57/BL6 mice. The murine pancreatic adenocarcinoma cell line PAN02, dispersed in
      MatrigelTM, was used for tumor induction. RESULTS: Tumors developed in all
      animals in both models. Tumor size was more consistent within the pancreatic tail
      group at 20 days following induction, with no evidence of metastatic disease.
      Animals in the pancreatic head injection group showed signs of reduced health by
      20 days following injection and developed jaundice. Microscopic liver metastases
      were noted in some of these animals at this time point. The overall survival of
      animals at 40 days following tumor induction was significantly lower in the
      pancreatic head injection group (0% vs. 35%; p < .001). Multiple liver metastases
      were noted in five of 10 (50%) animals in the head injection group, without
      evidence of peritoneal metastases. In the pancreatic tail injection group, 18 of
      20 (90%) animals had multiple peritoneal metastases, and nine of 20 (45%) animals
      had evidence of isolated liver deposits. Tumors in both regions of the pancreas
      had similar histologic characteristics, with a dense fibrotic stroma at the
      interface between the tumor and the normal pancreas. CONCLUSION: Pancreatic head
      and tail orthotopic cancer models produce consistent tumors, but the patterns of
      tumor spread and survival differ according to the site of injection.

PMID- 23957639
TI  - Pilates for people with multiple sclerosis who use a wheelchair: feasibility,
      efficacy and participant experiences.
AB  - PURPOSE: This mixed methods study aimed to explore the feasibility, efficacy and
      the participants' experiences of a Pilates programme for people with Multiple
      Sclerosis (pwMS) who use a wheelchair. METHOD: Fifteen pwMS took part in the 12
      week Pilates programme. At baseline and after 6 and 12 weeks of the programme,
      sitting stability, measured as maximum progression of the Centre of Pressure when
      leaning sideways (COPmax), posture, pain on a Visual Analogue Scale, function,
      fatigue and the impact of MS (MSIS29) were assessed. Ten participants took part
      in two focus groups within six weeks of the completion of the programme. RESULTS:
      Significant improvements at the 12-week assessment were found in COPmax (p =
      0.046), sitting posture (p = 0.004), pain in the shoulders (p = 0.005) and back
      (p = 0.005) and MSIS29 (p = 0.006). The majority of participants described
      various physical, functional, psychological and social benefits from
      participation that reflected increased confidence in activities of daily living.
      Enjoyment of the classes was expressed by all, and most wished to continue
      participation. CONCLUSIONS: Pilates appears to be efficacious in improving
      sitting stability and posture and decreasing pain and was also well tolerated by
      wheelchair users with MS. Further mixed methods studies are warranted.

PMID- 23957640
TI  - Prevention and treatment of hand oedema after stroke.
AB  - PURPOSE: As there is no evidence for a specific treatment for post-stroke-induced
      hand oedema, rehabilitation centre Blixembosch formalized a best practice
      protocol. We investigated whether the Blixembosch hand oedema protocol is usable
      in daily practice and leads to lower incidence (prevention) and shorter duration
      (treatment) compared with care as usual. METHODS: In a non-randomised comparative
      trial, we investigated 206 post-stroke patients admitted to two Dutch
      rehabilitation centres. Hand volumes were measured at least bi-weekly using a
      volumeter. Treatment was started according the protocol (Blixembosch) or
      following care as usual (Leijpark). Usability was assessed with a survey among
      professionals. RESULTS: In the Blixembosch group, 16% developed oedema after
      admission, compared with 21% in the control group (p = 0.019). Average duration
      of oedema (both developed before and after admission) was 6.5 weeks in the
      Blixembosch group compared with 3.1 weeks in the control group (p = 0.000).
      Professionals were positive about the protocol. CONCLUSION: The study showed that
      the protocol is usable in daily practice and has a small beneficial effect on
      hand oedema incidence rates compared with care as usual. The negative effect on
      duration of hand oedema could also be caused by the difference in prognosis
      between the two groups.

PMID- 23957641
TI  - Location of the bacteriophage P22 coat protein C-terminus provides opportunities
      for the design of capsid-based materials.
AB  - Rational design of modifications to the interior and exterior surfaces of virus
      like particles (VLPs) for future therapeutic and materials applications is based
      on structural information about the capsid. Existing cryo-electron microscopy
      based models suggest that the C-terminus of the bacteriophage P22 coat protein
      (CP) extends toward the capsid exterior. Our biochemical analysis through genetic
      manipulations of the C-terminus supports the model where the CP C-terminus is
      exposed on the exterior of the P22 capsid. Capsids displaying a 6xHis tag
      appended to the CP C-terminus bind to a Ni affinity column, and the addition of
      positively or negatively charged coiled coil peptides to the capsid results in
      association of these capsids upon mixing. Additionally, a single cysteine
      appended to the CP C-terminus results in the formation of intercapsid disulfide
      bonds and can serve as a site for chemical modifications. Thus, the C-terminus is
      a powerful location for multivalent display of peptides that facilitate nanoscale
      assembly and capsid modification. 

PMID- 23957642
TI  - A second look at efficacy criteria for onychomycosis: clinical and mycological
      cure.
AB  - BACKGROUND: Approval of topical onychomycosis drugs by regulatory agencies may be
      negatively impacted by an overly stringent definition of complete cure, which
      includes nail clearing plus mycological cure. OBJECTIVES: In this position paper,
      we discuss interpretation of mycological outcome and clinical trial length.
      METHODS: We reviewed data from seven international onychomycosis trials that
      enrolled subjects with positive KOH and dermatophyte-positive culture at
      screening followed by 48 weeks of treatment. Further, we examined 94 KOH
      positive/culture-negative week 52 follow-up samples for morphological hyphal
      damage. RESULTS: From 3054 samples collected at week 52 follow-up visits, 2360
      were culture-negative. However, a significant percentage (78.7%) of these
      subungual samples (n = 1857) remained KOH-positive. From the subset of follow-up
      samples examined for morphological changes, we identified hyphal breakage or
      distortion in 56 direct smears (60%), which may indicate nonviability.
      CONCLUSIONS: Reassessment of the definition of onychomycosis cure is critical.
      For clinical trials of topical agents, length of treatment should be re-examined.
      Further, in our experience, a high rate of subungual debris samples remained
      direct smear-positive while converting to negative culture. Evidence of
      morphological hyphal damage suggests that late-visit microscopic results may be
      false-positives. Therefore, the absence of clinical signs following an adequate
      washout period, coupled with a negative culture, with or without negative
      microscopy, should be considered the definition of onychomycosis cure.

PMID- 23957643
TI  - Dynamic changes of the ethylene biosynthesis in 'Jonagold' apple.
AB  - In this study, the short-term and dynamic changes of the ethylene biosynthesis of
      Jonagold apple during and after application of controlled atmosphere (CA) storage
      conditions were quantified using a systems biology approach. Rapid responses to
      imposed temperature and atmospheric conditions were captured by continuous online
      photoacoustic ethylene measurements. Discrete destructive sampling was done to
      understand observed changes of ethylene biosynthesis at the transcriptional,
      translational and metabolic level. Application of the ethylene inhibitor 1
      methylcyclopropene (1-MCP) allowed for the discrimination between ethylene
      mediated changes and ethylene-independent changes related to the imposed
      conditions. Online ethylene measurements showed fast and slower responses during
      and after application of CA conditions. The changes in 1-aminocyclopropane-1
      carboxylate synthase (ACS) activity were most correlated with changes in ACS1
      expression and regulated the cold-induced increase in ethylene production during
      the early chilling phase. Transcription of ACS3 was found ethylene independent
      and was triggered upon warming of CA-stored apples. Increased expression of ACO1
      during shelf life led to a strong increase in 1-aminocyclopropane-1-carboxylate
      oxidase (ACO) activity, required for the exponential production of ethylene
      during system 2. Expression of ACO2 and ACO3 was upregulated in 1-MCP-treated
      fruit showing a negative correlation with ethylene production. ACO activity never
      became rate limiting.

PMID- 23957644
TI  - Resorbable scaffolds modified with collagen type I or hydroxyapatite: in vitro
      studies on human mesenchymal stem cells.
AB  - Poly(L-lactide-co-glycolide) (PLGA) scaffolds of pore size within the range of
      250-320 MUm were produced by solvent casting/ porogen leaching method.
      Afterwards, they were modified through adsorption of collagen type I and
      incubation in simulated body fluid (SBF) to allow deposition of hydroxyapatite
      (HAp). The wettability of the scaffolds was measured by sessile drop test.
      Scanning electron microscopy (SEM) evaluation and energy dispersive X-ray
      analysis (EDX) were also performed. SEM evaluation and EDX analysis depicted the
      presence of HAp deposits and a collagen layer on the pore walls on the surface
      and in the bulk of the scaffolds. Wettability and water droplets penetration time
      within the scaffolds decreased considerably after applying modifications. Human
      mesenchymal stem cells (hMSC) were cultured on the scaffolds for 28 days and cell
      morphology, proliferation and differentiation as well as calcium deposition were
      evaluated. Lactate dehydrogenase (LDH) activity results revealed that cells
      cultured on tissue culture polystyrene (TCPS) exhibited high proliferation
      capacity. Cell growth on the scaffolds was slower in comparison to TCPS and did
      not depend on modification applied. On the other hand, osteogenic differentiation
      of hMSC as confirmed by alkaline phosphatase (ALP) activity and mineralization
      results was enhanced on the scaffolds modified with hydroxyapatite and collagen.

PMID- 23957645
TI  - Performance test of Nano-HA/PLLA composites for interface fixation.
AB  - OBJECTIVE: By in situ polymerization of poly-L-lactic acid (PLLA) and nano
      hydroxyapatite (Nano-HA), and finding the best proportion of composite, so as to
      get ideal interface fixation material. METHODS: According to a certain ratio (the
      mass fraction of Nano-HA, respectively, is 0%, 10%, 20%, 30% and 40%), composite
      PLLA and Nano-HA by in situ polymerization, and test the performance of this kind
      of new type of interface fixation such as, bending strength,compressive strength,
      elastic modulus, scanning electron microscopy (SEM) and degradation experiments
      in vitro. Then observe its mechanical properties, microstructure, the dispersion
      of Nano-HA in the PLLA and degradation rate of composite materials. RESULTS: 1.
      Mechanical tests show that with the increase of Nano-HA content, the tensile
      strength decreases and the elastic modulus increases; with Nano-HA content of
      20%, the bending strength of composite materials presents the peak value (156.8
      MPa). 2. SEM scan shows the fracture surface of pure PLLA is relatively smooth;
      with Nano-HA content of 10%, the fracture surface shows a large number of
      dimples, and is obvious rough; with Nano-HA content of 20%, the fracture surface
      is uneven, forming a large number of dimples; with Nano-HA content of 30% or
      more, the fracture surface becomes more flat, and there are some small dimples.
      3. Degradation experiments in vitro show the following: as the degradation time
      goes on, the pH values of degradation liquid is gradually reduced and the
      mechanical properties of composite materials also gradually have some decay.
      CONCLUSION: With Nano-HA content of 20%, the interface fixation material has a
      better mechanical properties and degradation properties. According to the best
      ratio, prepare Nano-HA/PLLA composite artificial materials with good performance.

PMID- 23957647
TI  - Case of seborrheic keratosis with underlying basal cell carcinoma suggesting a
      collision tumor.
AB  - Reports of seborrheic keratosis (SK) with concurrent malignant tumors are rare,
      but previous and recent reports - especially the co-manifestation of basal cell
      carcinomas (BCC) have added to the ongoing debate of the possibility of the
      development of BCC from SK. We report a rare case of SK with underlying BCC with
      scarcely accounted histopathological characteristics - reticulated type and
      nodular type, respectively - that showed no direct histological link between the
      two entities. We also carefully suggest that differences in histopathology
      (whether the two lesions are connected or not) may account for the possibility of
      incidental co-habitation. 

PMID- 23957646
TI  - Genetic basis of qualitative and quantitative resistance to powdery mildew in
      wheat: from consensus regions to candidate genes.
AB  - BACKGROUND: Powdery mildew (Blumeria graminis f. sp. tritici) is one of the most
      damaging diseases of wheat. The objective of this study was to identify the wheat
      genomic regions that are involved in the control of powdery mildew resistance
      through a quantitative trait loci (QTL) meta-analysis approach. This meta
      analysis allows the use of collected QTL data from different published studies to
      obtain consensus QTL across different genetic backgrounds, thus providing a
      better definition of the regions responsible for the trait, and the possibility
      to obtain molecular markers that will be suitable for marker-assisted selection.
      RESULTS: Five QTL for resistance to powdery mildew were identified under field
      conditions in the durum-wheat segregating population Creso * Pedroso. An
      integrated map was developed for the projection of resistance genes/ alleles and
      the QTL from the present study and the literature, and to investigate their
      distribution in the wheat genome. Molecular markers that correspond to candidate
      genes for plant responses to pathogens were also projected onto the map,
      particularly considering NBS-LRR and receptor-like protein kinases. More than 80
      independent QTL and 51 resistance genes from 62 different mapping populations
      were projected onto the consensus map using the Biomercator statistical software.
      Twenty-four MQTL that comprised 2-6 initial QTL that had widely varying
      confidence intervals were found on 15 chromosomes. The co-location of the
      resistance QTL and genes was investigated. Moreover, from analysis of the
      sequences of DArT markers, 28 DArT clones mapped on wheat chromosomes have been
      shown to be associated with the NBS-LRR genes and positioned in the same regions
      as the MQTL for powdery mildew resistance. CONCLUSIONS: The results from the
      present study provide a detailed analysis of the genetic basis of resistance to
      powdery mildew in wheat. The study of the Creso * Pedroso durum-wheat population
      has revealed some QTL that had not been previously identified. Furthermore, the
      analysis of the co-localization of resistance loci and functional markers
      provides a large list of candidate genes and opens up a new perspective for the
      fine mapping and isolation of resistance genes, and for the marker-assisted
      improvement of resistance in wheat.

PMID- 23957648
TI  - Changes in non-surgical management of stage III non-small cell lung cancer at a
      single institution between 2003 and 2010.
AB  - BACKGROUND: Concurrent chemo-radiotherapy (CON-CRT) is recommended for selected
      patients with stage III non-small cell lung cancer (NSCLC), but utilization
      varies. We assessed the response to national guidelines introduced in 2004 and
      the impact on outcomes. MATERIAL AND METHODS: Retrospective study of stage III
      NSCLC patients treated with radical intent non-surgical treatment during 2003
      2010 in a university medical center characterized by multidisciplinary
      assessment, routine use of four-dimensional computed tomography for radiotherapy
      planning, and rapid implementation of radiotherapy advances. RESULTS: Between
      2003 and 2010, 319/435 (73%) patients with stage III NSCLC received (chemo)
      radiotherapy. The number receiving CON-CRT in successive two-year periods
      increased from 13/48 (27%) - 40/80 (50%) - 63/90 (70%), to 74/101 (73%). Median
      overall survival (OS) from start of radiotherapy was 18.6 months for CON-CRT
      (190/319) and 17.4 months for sequential (SEQ), typically hypofractionated, CRT
      (90/319) (p = 0.78). Eleven months OS with radiotherapy alone (39/319) was
      significantly shorter (p = 0.006). OS did not differ between the four periods (p
      = 0.87). CON-CRT was not over-represented in the 16% of patients dying within
      five months of starting radiotherapy. CONCLUSIONS: Between 2003 and 2010, CON-CRT
      for stage III NSCLC was rapidly and safely increased. However, OS did not
      increase and, as practiced, did not differ between CON- or SEQ-CRT.

PMID- 23957649
TI  - Assessing patients' perceived bother from the gastrointestinal side effects of
      radiotherapy for localized prostate cancer: initial questionnaire development and
      validation.
AB  - BACKGROUND: The present study reports on the development and first steps of
      validation of the Gastrointestinal Side Effects Questionnaire (GISEQ), a measure
      of patient-reported gastrointestinal symptoms following local radiotherapy to the
      prostate. The questionnaire design provides a novel approach of assessment of
      side effects of prostate radiotherapy, by enabling measurement of patient
      perceived change in symptoms. MATERIAL AND METHODS: The eight-item GISEQ was
      administered to 130 prostate cancer patients referred to radiotherapy. Patients
      completed the GISEQ at four, eight and 15 weeks after start of radiotherapy. The
      psychometric properties including validity, reliability, responsiveness and
      feasibility were evaluated. The EORTC QLQ-C30 and QLQ-PR25 were chosen as
      comparative measures. RESULTS: Expert opinion supported content validity. For
      concurrent validity, correlation between the GISEQ and matching items in the
      EORTC questionnaires was moderate but significant (r > 0.41, p < 0.001). The
      responsiveness was adequate, indicated by changes in GISEQ scores over time
      corresponding to the effects of radiation. Internal consistency was satisfactory
      (overall Cronbach's alpha> 0.70). Sensitivity and specificity for items diarrhea,
      constipation and blood in stools ranged from 50% to 100% and from 68% to 100%,
      respectively. All items had a floor effect above 15%. The response rates ranged
      from 85% to 92% and missing items was < 0.8%, indicating good feasibility.
      CONCLUSIONS: The GISEQ showed satisfactory internal consistency and adequate
      content validity, concurrent validity and responsiveness. It is brief, easy to
      use and can be quickly evaluated, making it useful not only for research but
      possibly also for clinical settings. Modification of response scale and extension
      of items are potential improvements. Further work is needed to strengthen the
      psychometric qualities of the GISEQ and to evaluate its clinical use and
      potential effects of response shift and recall bias.

PMID- 23957650
TI  - Helical foldamer containing a combination of cyclopentane-1,2-diamine and 2,2
      dimethylmalonic acid.
AB  - We have developed new helical oligomers using a combination of (1S,2S)
      cyclopentane-1,2-diamine [(S,S)-CPDA] and 2,2-dimethylmalonic acid (DMM) residues
      as building blocks. In solution, the preferred secondary structure of the (S,S)
      tetramer 6 was a right-handed (P) helix, and that of the (R,R) tetramer ent-6 was
      a left-handed (M) helix. In the crystalline state, both 6 and the (S,S) pentamer
      7 folded into (P) 11-helices, and ent-6 folded into an (M) 11-helix with hydrogen
      bonds that were oriented in alternating directions. 

PMID- 23957651
TI  - Review article: small intestinal bacterial overgrowth--prevalence, clinical
      features, current and developing diagnostic tests, and treatment.
AB  - BACKGROUND: The symptoms and signs of small intestinal bacterial overgrowth
      (SIBO) are often identical to a variety of diseases and can lead to diagnostic
      confusion. AIMS: To review the diagnostic options for SIBO and present new
      investigative options for the condition. METHODS: A literature search was
      performed on MEDLINE, EMBASE and Web of Science for English articles and
      abstracts. Search terms included free text words and combinations of the
      following terms 'small intestinal bacterial overgrowth', 'small bowel bacterial
      overgrowth', 'diagnostic tests', 'treatment', 'antibiotics', 'probiotics',
      'metabonomics', 'proton nuclear magnetic resonance spectroscopy', 'electronic
      nose' and 'field asymmetric ion mobility spectrometry'. RESULTS: All of the
      available methods to test for SIBO have inherent limitations and no 'gold
      standard' diagnostic test for the condition exists. Accurate diagnosis of SIBO
      requires identification of bacterial species growing inappropriately within the
      small intestine and symptom response to antibiotics. Proton nuclear magnetic
      resonance spectroscopy, electronic nose technology and/or field asymmetric ion
      mobility spectrometry may represent better investigative options for the
      condition. CONCLUSIONS: Novel diagnostic options are needed to supplement or
      replace available tests.

PMID- 23957652
TI  - Evaluation of the quality of the general health information webpages in Spain:
      influence of page source.
AB  - The Internet, regardless of whether or not it is reliable, is considered the main
      source of health information. However, the lay-user does not know which sources
      offer good quality information. The main objective of the present study,
      therefore, was to evaluate the quality of Spanish health-related webpages, and to
      determine whether the webpage source influences this quality. To this end, 36
      webpages were selected through the PageRank(r) system. The webpages from all the
      Regional Health Services of Spain (19 sites) were also included. The quality
      evaluation, which was carried out by applying the Andalusian Health Quality
      Agency Test, indicated that the quality information offered by Spanish webpages
      is very low, since no site reached the maximum score. In addition, several
      important aspects, including those related with personal data management and the
      updating of information, were not considered by most of the evaluated pages. In
      summary, this work shows that quality of the health information webpages in Spain
      is generally low, and draws particular attention to certain responsibilities,
      that are not met by most evaluated webpages, including sites from the Regional
      Health Services. 

PMID- 23957654
TI  - One-step overall water splitting under visible light using multiband InGaN/GaN
      nanowire heterostructures.
AB  - The conversion of solar energy into hydrogen via water splitting process is one
      of the key sustainable technologies for future clean, storable, and renewable
      source of energy. Therefore, development of visible light-responsive and
      efficient photocatalyst material has been of immense interest, but with limited
      success. Here, we show that overall water splitting under visible-light
      irradiation can be achieved using a single photocatalyst material. Multiband
      InGaN/GaN nanowire heterostructures, decorated with rhodium (Rh)/chromium-oxide
      (Cr2O3) core-shell nanoparticles can lead to stable hydrogen production from pure
      (pH ~ 7.0) water splitting under ultraviolet, blue and green-light irradiation
      (up to ~560 nm), the longest wavelength ever reported. At ~440-450 nm
      wavelengths, the internal quantum efficiency is estimated to be ~13%, the highest
      value reported in the visible spectrum. The turnover number under visible light
      well exceeds 73 in 12 h. Detailed analysis further confirms the stable
      photocatalytic activity of the nanowire heterostructures. This work establishes
      the use of metal-nitrides as viable photocatalyst for solar-powered artificial
      photosynthesis for the production of hydrogen and other solar fuels. 

PMID- 23957653
TI  - Synthesis of dihydrobenzofurans with quaternary carbon center under mild and
      neutral conditions.
AB  - A new method has been developed for the construction of dihydrobenzofurans from O
      aryloxime ethers bearing an alpha-cyano group using a sequential regioselective
      isomerization/[3,3]-sigmatropic rearrangement/cyclization reaction in MeOH
      without any catalysts under neutral conditions at ambient temperature. The
      current transformation provides environmentally benign and atom-economical access
      to a variety of dihydrobenzofurans containing a quaternary carbon from readily
      available cyclic and acyclic oxime ethers. 

PMID- 23957655
TI  - Nitric oxide releasing Tygon materials: studies in donor leaching and localized
      nitric oxide release at a polymer-buffer interface.
AB  - Tygon is a proprietary plasticized poly(vinyl chloride) polymer that is used
      widely in bioapplications, specifically as extracorporeal circuits. To overcome
      issues with blood clot formation and infection associated with the failure of
      these medical devices upon blood contact, we consider a Tygon coating with the
      ability to release the natural anticlotting and antibiotic agent, nitric oxide
      (NO), under simulated physiological conditions. These coatings are prepared by
      incorporating 20 w/w% S-nitrosoglutathione (GSNO) donor into a Tygon matrix.
      These films release NO on the order of 0.64 +/- 0.5 * 10(-10) mol NO cm(-2) min(
      1), which mimics the lower end of natural endothelium NO flux. We use a
      combination of assays to quantify the amount of GSNO that is found intact at
      different time points throughout the film soak, as well as monitor the total
      thiol content in the soaking solution due to any analyte that has leached from
      the polymer film. We find that a burst of GSNO is released from the material
      surface within 5 min to 1 h of soaking, which only represents 0.25% of the total
      GSNO contained in the film. After 1 h of film soak, no additional GSNO is
      detected in the soaking solution. By further considering the total thiol content
      in solution relative to the intact GSNO, we demonstrate that the amount of GSNO
      leached from the material into the buffer soaking solution does not contribute
      significantly to the total NO released from the GSNO-incorporated Tygon film
      (<10% total NO). Further surface analysis using SEM-EDS traces the elemental S on
      the material surface, demonstrating that within 5 min -1 h soaking time, 90% of
      the surface S is removed from the material. Surface wettability and roughness
      measurements indicate no changes between the GSNO-incorporated films pre- to
      postsoak that will be significant toward the adsorption of biological components,
      such as proteins, relative to the presoaked donor-incorporated film. Overall, we
      demonstrate that, for a 20 w/w% GSNO-incorporated Tygon film, relatively minimal
      GSNO leaching is experienced, and the lost GSNO is from the material surface.
      Varying the donor concentration from 5 to 30 w/w% GSNO within the film does not
      result in significantly different NO release profiles. Additionally, the steady
      NO flux associated with the system is predominantly due to localized release from
      the material, and not donor lost to soaking solution. The surface properties of
      these materials generally imply that they are useful for blood-contacting
      applications. 

PMID- 23957656
TI  - Discordance between nuclear and mitochondrial genomes in sexual and asexual
      lineages of the freshwater snail Potamopyrgus antipodarum.
AB  - The presence and extent of mitonuclear discordance in coexisting sexual and
      asexual lineages provides insight into 1) how and when asexual lineages emerged,
      and 2) the spatial and temporal scales at which the ecological and evolutionary
      processes influencing the evolution of sexual and asexual reproduction occur.
      Here, we used nuclear single-nucleotide polymorphism (SNP) markers and a
      mitochondrial gene to characterize phylogeographic structure and the extent of
      mitonuclear discordance in Potamopyrgus antipodarum. This New Zealand freshwater
      snail is often used to study the evolution and maintenance of sex because
      obligately sexual and obligately asexual individuals often coexist. While our
      data indicate that sexual and asexual P. antipodarum sampled from the same lake
      population are often genetically similar, suggesting recent origin of these
      asexuals from sympatric sexual P. antipodarum, we also found significantly more
      population structure in sexuals vs. asexuals. This latter result suggests that
      some asexual lineages originated in other lakes and/or in the relatively distant
      past. When comparing mitochondrial and nuclear population genetic structure, we
      discovered that one mitochondrial haplotype ('1A') was rare in sexuals, but
      common and widespread in asexuals. Haplotype 1A frequency and nuclear genetic
      diversity were not associated, suggesting that the commonness of this haplotype
      cannot be attributed entirely to genetic drift and pointing instead to a role for
      selection. 

PMID- 23957657
TI  - Interleukin-18, CRP and procalcitonin levels in vesicoureteral reflux and reflux
      nephropathy.
AB  - BACKGROUND: Some patients with vesicoureteral reflux (VUR) develop reflux
      nephropathy (RN) and a number of them progress to chronic kidney disease (CKD).
      However, it is unclear to predict which patient will develop RN and/or CKD. The
      aim of this study is to evaluate the role of Interleukin-18 (IL-18), C-reactive
      protein (CRP) and procalcitonin (PCT) as an indicator of RN in VUR. METHODS:
      Ninety-three children aged 3.5-16 years with primary VUR were enrolled. Patients
      were divided into two groups according to the presence of renal scarring (RS).
      CRP, PCT, blood urea nitrogen (BUN), serum creatinine (Scr), urinary protein
      (Up), creatinine (Ucr) and microalbumin (Umalb), serum and urine IL-18 levels
      were determined during urinary tract infection (UTI) free episode. RESULTS: BUN,
      Scr, Up/Ucr and Umalb/Ucr concentrations were higher whereas calculated
      creatinine clearance (Ccr) values were lower in RS (+) group compared to RS (-)
      group. CRP, PCT, serum and urine IL-18 levels and mean urine IL-18/Cr
      concentrations were similar in both groups. Serum and urine IL-18 levels did not
      differ according to the grade of VUR. No significant correlation was found
      between CRP, PCT and IL-18. CONCLUSIONS: Proteinuria and microalbuminuria are
      valuable hallmarks of RN. CRP and PCT seem not to be reliable indicators of RN in
      VUR patients. Moreover, serum and urine IL-18 might not predict RN.

PMID- 23957658
TI  - Evaluation of ASPIRE trial: a Phase III pivotal registration trial, using
      intracoronary administration of Generx (Ad5FGF4) to treat patients with recurrent
      angina pectoris.
AB  - The ASPIRE study (a randomized, controlled, parallel group, multicenter study to
      evaluate the efficacy and safety of Ad5FGF-4 using adenosine single-photon
      emission computed tomography (SPECT) myocardial perfusion imaging in patients
      with stable angina pectoris) (ClinicalTrials.gov Identifier: NCT01550614) is a
      100-patient, controlled, randomized, multicenter study conducted in six centers
      in Russia. This trial will assess the therapeutic efficacy of Generx (Ad5-FGF4)
      using rest and stress SPECT following a one-time, catheter-based administration.
      Adenovirus-based antianginal therapy represents an interesting option but the
      difficulties observed in the various trials carried out to date illustrate the
      complexity of the issue. Large and well-designed studies should be encouraged to
      provide definitive answers to this important research question. 

PMID- 23957659
TI  - Childhood adversity as a risk for cancer: findings from the 1958 British birth
      cohort study.
AB  - BACKGROUND: To analyse whether Adverse Childhood Experiences (ACE) are associated
      with an increased risk of cancer. METHODS: The National child development study
      (NCDS) is a prospective birth cohort study with data collected over 50 years. The
      NCDS included all live births during one week in 1958 (n=18558) in Great Britain.
      Self-reported cancer incidence was based on 444 participants reporting having had
      cancer at some point and 5694 reporting never having cancer. ACE was measured
      using reports of: 1) child in care, 2) physical neglect, 3) child's or family's
      contact with the prison service, 4) parental separation due to divorce, death or
      other, 5) family experience of mental illness & 6) family experience of substance
      abuse. The resulting variable had three categories, no ACEs/ one ACE/ 2+ACEs and
      was used to test for a relationship with cancer. Information on socioeconomic
      characteristics, pregnancy and birth were extracted as potential confounders.
      Information on adult health behaviours, socioeconomic environment, psychological
      state and age at first pregnancy were added to the models. Multivariate models
      were run using multiply-imputed data to account for missing data in the cohort.
      RESULTS: The odds of having a cancer before 50 y among women increased twofold
      for those who had 2+ ACEs versus those with no ACEs, after adjusting for adult
      factors and early life confounders (OR: 2.1, 95% CI: 1.42-3.21, p<0.001).
      CONCLUSION: These findings suggest that cancer risk may be influenced by exposure
      to stressful conditions and events early on in life. This is potentially
      important in furthering our understanding of cancer aetiology, and consequently
      in redirecting scientific research and developing appropriate prevention
      policies.

PMID- 23957660
TI  - Substantial Cd-Cd bonding in Ca6PtCd11: a condensed intermetallic phase built of
      pentagonal Cd7 and rectangular Cd4/2Pt pyramids.
AB  - The novel intermetallic Ca6PtCd11 is orthorhombic, Pnma, Z = 4, with a =
      18.799(2) A, b = 5.986(1) A, c = 15.585(3) A. The heavily condensed network
      contains three types of parallel cadmium chains: apically strongly interbonded
      Cd7 pentagonal bipyramids, linear Cd arrays, and rectangular Cd4/2Pt pyramids.
      All of the atoms have 11-13 neighbors. Calculations by means of the linear muffin
      tin orbitals method in the atomic spheres approximation indicate that some Cd-Cd
      interactions correspond to notably high Hamilton populations (1.07 eV per average
      bond) whereas the Ca-Ca covalent interactions (integrated crystal orbital
      Hamiltonian population) are particularly small (0.17 eV/bond). (Pt-Cd
      interactions are individually greater but much less in aggregate.) The Ca-Ca
      separations are small, appreciably less than the single bond metallic diameters,
      and unusually uniform (Delta = 0.14 A). The Cd atoms make major contributions to
      the stability of the phase via substantial 5s and 5p bonding, which include back
      donation of Cd 5s, 5p and Pt 5d into Ca 3d states in the principal bonding modes
      for Ca-Cd and Ca-Pt. Bonding Ca-Ca, Ca-Cd, and Cd-Cd states remain above EF, and
      some relative oxidation of Ca in this structure seems probable. Ca6PtCd11 joins a
      small group of other phases in which Cd clustering and Cd-Cd bonding are
      important. 

PMID- 23957662
TI  - Percutaneous medial saphenous artery approach for Swine central artery access.
AB  - A percutaneous medial saphenous artery catheterization technique for swine
      femoral access is described. The medial saphenous artery is accessed with a 22
      gauge catheter-over-needle assembly, followed by 4-Fr 10-cm sheath insertion
      using the Seldinger technique. The 4-Fr sheath is subsequently exchanged over a
      0.035-inch guidewire for a 5-Fr sheath to establish central artery access. The
      technique was applied to seven vessels in five swine, with successful
      catheterization in five vessels. The reason for failure was technical difficulty
      in one case and vasospasm in the other. Central artery access was still possible
      through direct exposure and puncture of the medial saphenous artery or the
      femoral artery. This technique may provide an alternative option for central
      artery access in swine. However, improvement in more reliable catheterization is
      warranted.

PMID- 23957661
TI  - Malaria's deadly grip: cytoadhesion of Plasmodium falciparum-infected
      erythrocytes.
AB  - Cytoadhesion of Plasmodium falciparum-infected erythrocytes to host
      microvasculature is a key virulence determinant. Parasite binding is mediated by
      a large family of clonally variant adhesion proteins, termed P. falciparum
      erythrocyte membrane protein 1 (PfEMP1), encoded by var genes and expressed at
      the infected erythrocyte surface. Although PfEMP1 proteins have extensively
      diverged under opposing selection pressure to maintain ligand binding while
      avoiding antibody-mediated detection, recent work has revealed they can be
      classified into different groups based on chromosome location and domain
      composition. This grouping reflects functional specialization of PfEMP1 proteins
      for different human host and microvascular binding niches and appears to be
      maintained by gene recombination hierarchies. Inone extreme, a specific PfEMP1
      variant is associated with placental binding and malaria during pregnancy, while
      other PfEMP1 subtypes appear to be specialized for infection of malaria naive
      hosts. Here, we discuss recent findings on the origins and evolution of the var
      gene family, the structure-function of PfEMP1 proteins, and a distinct subset of
      PfEMP1 variants that have been associated with severe childhood malaria.

PMID- 23957663
TI  - Dental malocclusion is not related to temporomandibular joint clicking: a
      logistic regression analysis in a patient population.
AB  - OBJECTIVES: To assess the association of several dental malocclusion features
      with temporomandibular joint (TMJ) click sounds in a population of
      temporomandibular disorder (TMD) patients. MATERIALS AND METHODS: Four hundred
      forty-two TMD patients (72% female; 32.2 +/- 5.7 years, range 25-44 years) were
      divided into a TMJ clicking and a no-TMJ clicking group, based on the Research
      Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) assessment. Seven
      occlusal features were recorded for each patient: (1) posterior crossbite, (2)
      overbite, (3) open bite, (4) overjet, (5) mediotrusive and (6) laterotrusive
      interferences and (7) retruded contact position to maximum intercuspation (RCP
      MI) slide length. A logistic regression model was created to estimate the
      association of occlusal features with TMJ clicking. RESULTS: The difference
      between the groups as for the prevalence of the various occlusal features was
      generally not statistically significant, with minor exceptions. Mediotrusive
      interferences (P  =  .015) and RCP-MI slide >=2 mm (P  =  .001) were the two
      occlusal features that were associated with the probability of having TMJ
      clicking, even if the adjusted odds ratios for TMJ clicking were low for both
      variables (1.63 and 1.89, respectively). Moreover, the amount of variance in the
      prevalence of TMJ clicking that was predicted by the final model was as low as
      4.5% (R(2)  =  0.045). CONCLUSIONS: Findings from the present investigation
      suggested that in a population of TMD patients, the contribution of dental
      malocclusion features to predict TMJ click sounds is minimal with no clinical
      relevance.

PMID- 23957664
TI  - Accuracy of laser-scanned models compared to plaster models and cone-beam
      computed tomography.
AB  - OBJECTIVE: To compare the accuracy of measurements obtained from the three
      dimensional (3D) laser scans to those taken from the cone-beam computed
      tomography (CBCT) scans and those obtained from plaster models. MATERIALS AND
      METHODS: Eighteen different measurements, encompassing mesiodistal width of teeth
      and both maxillary and mandibular arch length and width, were selected using
      various landmarks. CBCT scans and plaster models were prepared from 60 patients.
      Plaster models were scanned using the Ortho Insight 3D laser scanner, and the
      selected landmarks were measured using its software. CBCT scans were imported and
      analyzed using the Avizo software, and the 26 landmarks corresponding to the
      selected measurements were located and recorded. The plaster models were also
      measured using a digital caliper. Descriptive statistics and intraclass
      correlation coefficient (ICC) were used to analyze the data. RESULTS: The ICC
      result showed that the values obtained by the three different methods were highly
      correlated in all measurements, all having correlations>0.808. When checking the
      differences between values and methods, the largest mean difference found was
      0.59 mm+/-0.38 mm. CONCLUSIONS: In conclusion, plaster models, CBCT models, and
      laser-scanned models are three different diagnostic records, each with its own
      advantages and disadvantages. The present results showed that the laser-scanned
      models are highly accurate to plaster models and CBCT scans. This gives general
      clinicians an alternative to take into consideration the advantages of laser
      scanned models over plaster models and CBCT reconstructions.

PMID- 23957665
TI  - Photos vs silhouettes for evaluation of profile esthetics between white and black
      evaluators.
AB  - OBJECTIVE: To determine whether photos or silhouettes are adequate methods for
      evaluating the esthetic profiles of black subjects and whether black and white
      evaluators have different preferences for esthetic profiles. MATERIALS AND
      METHODS: One photographic record of the profile of a black female patient with
      accentuated dental bimaxillary dentoalveolar protrusion was randomly selected.
      The image of the patient's profile was altered to produce a series of seven
      photos and seven silhouettes (a total of 14 images) with different lip positions
      but uniform distances in relation to the esthetic plane created by Ricketts (line
      E). Fifty black and 50 white lay evaluators were invited to enumerate the photos
      and silhouettes, produced according to the lip position, in the order in which
      they considered most esthetically pleasing. RESULTS: The number of preferences
      found to be within the esthetic norm was slightly higher among the photographs
      than among the silhouettes; the esthetic profile with a deviation of -2 mm from
      line E was elected as the most attractive, and the esthetic pattern with a
      deviation of +6 mm from the normal line E was considered the least attractive.
      There were no statistically significant differences between the preferences
      related to the variables race, sex, and educational background. CONCLUSIONS: The
      esthetic attractiveness of the facial profiles of black subjects in photos and
      silhouettes was evaluated in a similar manner among black and white evaluators.
      Among both black and white evaluators, the greatest preference was for the
      slightly concave profile, which was within the limit considered standard.

PMID- 23957666
TI  - Differential use of antivirals for treatment of patients with influenza
      A(H1N1)pdm09 in Germany.
AB  - BACKGROUND: The World Health Organization recommends early antiviral treatment
      for patients with severe influenza illness or those at increased risk for severe
      illness. OBJECTIVES: The aim of this study was to determine the proportion of
      cases with laboratory-confirmed A(H1N1)pdm09 infection that have been treated
      with antivirals in Germany during the pandemic (H1N1) 2009 and to investigate
      factors associated with the use of antivirals. METHODS: We analyzed cases with
      laboratory-confirmed A(H1N1)pdm09 infection notified to national health
      authorities in Germany between week 29/2009 and week 17/2010 using multivariable
      logistic regression. Severity of disease was defined by pneumonia or death.
      RESULTS AND CONCLUSIONS: Of 160,804 cases with laboratory-confirmed A(H1N1)pdm09
      infection, 22% were treated with antivirals. Cases with severe disease were more
      likely to be treated with antivirals than cases without severe disease (odds
      ratio=1.66; 95% confidence interval: 1.46-1.89). In the group with at least one
      underlying medical condition, only children aged between 1 and 4 years had
      significant lower odds for receiving antiviral treatment compared with cases in
      the age group 15 to 49 years (odds ratio=0.75; 95% confidence interval: 0.6
      0.94). In conclusion, the implementation of international recommendations on use
      of antivirals differed according to the age of patients in Germany during the
      pandemic (H1N1) 2009. This indicates that the potential of antivirals to prevent
      severe influenza might not have been fully exhausted. The reasons leading to the
      observed differences in patient management need to be investigated.

PMID- 23957667
TI  - Langerhans cell histiocytosis: a retrospective analysis in a Korean tertiary
      hospital from 2003 to 2012.
AB  - Epidemiological study of Langerhans cell histiocytosis (LCH) has been limited due
      to its rarity and multisystemic involvement. The aim of this study was to
      investigate the epidemiological features of LCH via the clinical data warehouse
      (CDW). Clinical data of 30 LCH patients from the all departments of a tertiary
      referral hospital between 2003 and 2012 were analyzed retrospectively by
      searching the CDW. The male-to-female ratio was 2.8:1. The age of onset ranged 7
      days to 57 years with a median of 13 years. Of the patients, 36.7% presented
      initial symptoms before the age of 10 years. The involved organs at diagnosis
      were: bone (66.7%), skin (16.7%), lungs (13.3%) and lymph node (3.3%). For all of
      the 30 cases, there were 31 disease sites because of a single case of
      multisystemic disease involving both skin and bone. Of the 96.7% of patients with
      single-system disease, 69.0% had bony involvement. This study elucidated the
      clinical features of LCH from all the departments of a tertiary hospital via the
      CDW, which suggests a potential role of the CDW as a new epidemiological approach
      for rare diseases.

PMID- 23957668
TI  - De novo transcriptome assembly of drought tolerant CAM plants, Agave deserti and
      Agave tequilana.
AB  - BACKGROUND: Agaves are succulent monocotyledonous plants native to xeric
      environments of North America. Because of their adaptations to their environment,
      including crassulacean acid metabolism (CAM, a water-efficient form of
      photosynthesis), and existing technologies for ethanol production, agaves have
      gained attention both as potential lignocellulosic bioenergy feedstocks and
      models for exploring plant responses to abiotic stress. However, the lack of
      comprehensive Agave sequence datasets limits the scope of investigations into the
      molecular-genetic basis of Agave traits. RESULTS: Here, we present comprehensive,
      high quality de novo transcriptome assemblies of two Agave species, A. tequilana
      and A. deserti, built from short-read RNA-seq data. Our analyses support
      completeness and accuracy of the de novo transcriptome assemblies, with each
      species having a minimum of approximately 35,000 protein-coding genes. Comparison
      of agave proteomes to those of additional plant species identifies biological
      functions of gene families displaying sequence divergence in agave species.
      Additionally, a focus on the transcriptomics of the A. deserti juvenile leaf
      confirms evolutionary conservation of monocotyledonous leaf physiology and
      development along the proximal-distal axis. CONCLUSIONS: Our work presents a
      comprehensive transcriptome resource for two Agave species and provides insight
      into their biology and physiology. These resources are a foundation for further
      investigation of agave biology and their improvement for bioenergy development.

PMID- 23957669
TI  - Dietary consumption of meat, fat, animal products and advanced glycation end
      products and the risk of Barrett's oesophagus.
AB  - BACKGROUND: Advanced glycation end-products (AGEs) are found in high quantity in
      high-fat foods and meat cooked at high temperature. AGEs have been shown to
      contribute to chronic inflammation and oxidative stress in humans. AIM: To
      investigate the associations between consumption of meat, fat and AGEs, and the
      risk of Barrett's oesophagus (BO). METHODS: We conducted a case-control study
      using data from the patients who were scheduled for elective
      esophagogastroduodenoscopy (EGD) and from a random sample of patients who were
      identified at primary care clinics. Daily consumption of meat, fat and Nepsilon
      (carboxymethyl) lysine (CML), a major type of AGEs, was derived from the food
      frequency questionnaire (FFQ). Multivariate logistic regression models were used
      to estimate the odds ratio (OR) and its 95% confidence interval (CI) for BO.
      RESULTS: A total of 151 cases with BO and 777 controls without BO completed the
      FFQ. The multivariate OR (95% CI) for BO was 1.91 (1.07-3.38) for total meat,
      1.80 (1.02-3.16) for saturated fat and 1.63 (0.96-2.76) for CML-AGE, when the
      highest tertile of intake was compared with the lowest. The association for total
      meat was attenuated to 1.61 (0.82-3.16), and that for saturated fat to 1.54 (0.81
      2.94) after adjusting for CML-AGE. CONCLUSIONS: Higher consumption of total meat,
      saturated fat or possibly CML-AGE was associated with an increased risk of
      Barrett's oesophagus. CML-AGE may partly explain the association between total
      meat and saturated fat consumption and the risk of Barrett's oesophagus.

PMID- 23957670
TI  - Comparative cytogenetic study on Trifolium subterraneum (2n = 16) and Trifolium
      israeliticum (2n = 12).
AB  - Changes in chromosome number have played an important role in the evolution of
      the genus Trifolium. Along with a few species of polyploid origin there are
      several cases of dysploidy as evidenced by the presence of four basic chromosome
      numbers (x = 8, 7, 6, 5). Trifolium subterraneum and Trifolium israeliticum are
      related species with chromosome complements 2n = 16 and 2n = 12, respectively.
      Although they represent an interesting case of speciation based on chromosome
      number reduction, no attempts to demonstrate their cytogenetic affinity have been
      carried out to date. With this study we performed a comparative cytogenetic study
      with the purpose of clarifying the evolutionary relationship between these
      species and to verify whether genomic rearrangements, other than modification of
      the chromosome number, are associated with the speciation process. Although
      karyomorphological analysis supports the hypothesis that chromosome
      rearrangements had a role in the reduction of the chromosome number, the physical
      mapping of the rDNA sequences revealed a significant remodelling of the 45S and
      5S rDNA sites that greatly contributed to the differentiation of the 2n = 16 and
      2n = 12 karyotypes. The nucleotide analysis of 5S rDNA repeats confirmed that the
      two species are related but constitute distinct entities. The observed genomic
      changes lead to the hypothesis that the 2n = 12 species is the result of an
      evolutionary pathway that passed through intermediate forms. It cannot be
      excluded that the most direct ancestor of T. israeliticum is a species with 2n =
      14. 

PMID- 23957672
TI  - Comparative analysis of the IGF2 and ZBED6 gene variants and haplotypes reveals
      significant effect of growth traits in cattle.
AB  - Muscle growth is a complex phenomenon regulated by many factors, whereby net
      growth results from the combined action of synthesis and turnover. Insulin-like
      growth factor 2 (IGF2) is a fetal growth and differentiation factor that plays an
      important role in muscle growth and in myoblast proliferation and
      differentiation; Zinc finger, BED-type containing 6 (ZBED6) is a novel
      transcription factor that was identified and shown to act as a repressor of IGF2
      transcription in skeletal muscle. In this study, a total of seven single
      nucleotide polymorphisms (SNPs) were identified, four SNPs in intron 8 of IGF2
      and one promoter SNP and two missense mutations in the coding region of ZBED6,
      two of which were in complete linkage disequilibrium (LD) in the bovine IGF2. The
      58 haplotypes were inferred in 1522 individuals representing four purebred cattle
      breeds from China. The seven SNPs, 79 and 66 combined diplotypes were revealed
      for association with body mass in Nanyang and Jiaxian cattle populations at five
      different ages (P < 0.05 or 0.01). The mutant-type variants and haplotype 58
      (likely in LD with the beneficial quantitative trait nucleotide allele) was
      superior for body mass; the heterozygote diplotype of the most common haplotypes
      58 was associated with higher body mass compared to either heterozygote or
      homozygote. The statistical analyses indicated that the mutant-type variants and
      haplotypes are significantly associated with body mass in study cattle
      populations at different ages. These data demonstrate that variants and
      haplotypes are associated with growth traits, and these results may provide
      important biological insights into the phenotypic differentiation that is
      associated with adaptation and specialization of cattle breeds. 

PMID- 23957671
TI  - A comparative approach expands the protein-protein interaction node of the immune
      receptor XA21 in wheat and rice.
AB  - The rice (Oryza sativa) OsXA21 receptor kinase is a well-studied immune receptor
      that initiates a signal transduction pathway leading to resistance to Xanthomonas
      oryzae pv. oryzae. Two homologs of OsXA21 were identified in wheat (Triticum
      aestivum): TaXA21-like1 located in a syntenic region with OsXA21, and TaXA21
      like2 located in a nonsyntenic region. Proteins encoded by these two wheat genes
      interact with four wheat orthologs of known OsXA21 interactors. In this study, we
      screened a wheat yeast-two-hybrid (Y2H) library using the cytosolic portion of
      TaXA21-like1 as bait to identify additional interactors. Using full-length T.
      aestivum and T. monococcum proteins and Y2H assays we identified three novel
      TaXA21-like1 interactors (TaARG, TaPR2, TmSKL1) plus one previously known in rice
      (TaSGT1). An additional full-length wheat protein (TaCIPK14) interacted with
      TaXA21-like2 and OsXA21 but not with TaXA21-like1. The interactions of TaXA21
      like1 with TmSKL1 and TaSGT1 were also observed in rice protoplasts using
      bimolecular fluorescence complementation assays. We then cloned the rice homologs
      of the novel wheat interactors and confirmed that they all interact with OsXA21.
      This last result suggests that interspecific comparative interactome analyses can
      be used not only to transfer known interactions from rice to wheat, but also to
      identify novel interactions in rice. 

PMID- 23957673
TI  - Karyotype stability in the genus Phaseolus evidenced by the comparative mapping
      of the wild species Phaseolus microcarpus.
AB  - The genus Phaseolus L. (Fabaceae) is monophyletic and comprises approximately 75
      species distributed into two principal clades. The five cultivated species,
      including the common bean (Phaseolus vulgaris), were placed in clade B. Clade A
      comprises only wild species, with more limited distribution. In the present work,
      bacterial artificial chromosomes (BACs) previously mapped in common bean (2n =
      22) were used as probes in fluorescent in situ hybridization (FISH) in this
      comparative study of Phaseolus microcarpus (2n = 22), a species from clade A. We
      also analyzed the chromomycin A3 (CMA)/4',6-diamidino-2-phenylindole (DAPI)
      banding pattern and the localization of rDNA and telomeric DNA sites. The single
      45S rDNA site from P. microcarpus was mapped to chromosome 6, showing
      conservation to the P. vulgaris homeolog. Of the two 5S rDNA sites identified in
      both species, only the site on chromosome 10 appeared conserved. In spite of the
      phylogenetic distance between the two species, all of the single-copy BACs
      demonstrated conservation of synteny. However, four collinearity breaks were
      observed, probably caused by para- and pericentric inversions. Some variation in
      the repetitive fraction of the genome was also observed. Thus, a broader analysis
      of the genus confirms that few, rare inversions seem to represent the main
      karyotype changes during the evolution of this genus. 

PMID- 23957674
TI  - Population genetic structure and genetic diversity of soybean aphid collections
      from the USA, South Korea, and Japan.
AB  - Following its recent invasion of North America, the soybean aphid (Aphis glycines
      Matsumura) has become the number one insect pest of soybean (Glycine max L.
      Merr.) in the north central states of the USA. A few studies have been conducted
      on the population genetic structure and genetic diversity of the soybean aphid
      and the source of its invasion in North America. Molecular markers, such as
      simple sequence repeats (SSRs) are very useful in the evaluation of population
      structure and genetic diversity. We used 18 SSR markers to assess the genetic
      diversity of soybean aphid collections from the USA, South Korea, and Japan. The
      aphids were collected from two sites in the USA (Indiana and South Dakota), two
      sites in South Korea (Yeonggwang district and Cheonan city), and one site in
      Japan (Utsunomiya). The SSR markers were highly effective in differentiating
      among aphid collections from different countries. The level of differentiation
      within each population and among populations from the same country was limited,
      even in the case of the USA where the two collection sites were more than 1200 km
      apart. 

PMID- 23957675
TI  - Comparative analysis of genetic diversity in Canadian barley assessed by SSR,
      DarT, and pedigree data.
AB  - The aim of this study was to measure genetic diversity and population structure
      among 92 Canadian barley cultivars using two types of molecular markers (SSRs and
      DArTs) and pedigree data. A total of 368 alleles were identified at 50 SSR loci.
      The number of alleles per locus ranged between 2 and 13 ([Formula: see text] =
      7.36) and PIC values ranged from 0.34 to 0.86 ([Formula: see text] = 0.69). For
      the biallelic DArT markers, the genetic distance matrix was based on 971 markers
      whose PIC values ranged between 0.06 and 0.50 ([Formula: see text] = 0.39). A
      third distance matrix was computed based on the kinship coefficient. Clustering
      of genotypes was performed based on the genetic distance matrix and the three
      dendrograms obtained showed the genetic relationships among barley cultivars. The
      topological similarity of the three dendrograms was estimated using a congruence
      index and showed the three dendrograms to be in very good agreement. Statistical
      analysis also showed a highly significant correlation between the SSR and DArT
      matrices (r = 0.80, p < 0.002) compared with lower yet significant correlations
      of the pedigree data with both marker types (r = 0.46, p < 0.002; r = 0.52, p <
      0.002). Finally, we assessed linkage disequilibrium in this germplasm and found
      it to be quite extensive, as the mean distance between marker pairs with
      significant (P < 0.001) r(2) values >0.5 was 3.8 cM. Information obtained from
      comparing results of different genetic diversity estimation methods should be
      useful for the improvement and conservation of barley genetic resources. 

PMID- 23957676
TI  - Cloning and characterization of serpin-like genes from the striped rice stem
      borer, Chilo suppressalis.
AB  - Serpins, also called serine proteinase inhibitors, are widely distributed in
      eukaryotes. In insects, serpins play important roles in regulating immune
      responses, gut physiology, and other processes. Here, we report the cloning and
      characterization of 12 serpin-like cDNAs from the striped rice stem borer (Chilo
      suppressalis), a major rice pest. The putative proteins share significant
      sequence similarity with known insect serpins, especially those from
      lepidopterons. Analysis of functional domains revealed that nine of the cloned
      serpins are putative trypsin- or chymotrypsin-like inhibitors; two are mixed-type
      serpins that may act as inhibitors for trypsins, elastases, or thrombin; and the
      remaining one is truncate. The potential functions of these serpins in
      interacting with host plants were also investigated by analyzing tissue-specific
      expression and the impact of different host plant genotypes on gene expression.
      Our results provide a foundation for future studies on the role of serpins in gut
      physiology in the striped rice stem borer, and also useful information for
      comparative analyses of serpins from different insect species. 

PMID- 23957678
TI  - Anorectal necrosis after paracetamol abuse.

PMID- 23957679
TI  - Synthesis of all four stereoisomers of 3-(tert-butoxycarbonyl)-3
      azabicyclo[3.1.0]hexane-2-carboxylic acid.
AB  - A synthesis of all four stereoisomers of 3-(tert-butoxycarbonyl)-3
      azabicyclo[3.1.0]hexane-2-carboxylic acid has been developed, thereby
      significantly shortening the known literature procedures for the syntheses of
      these unnatural amino acids. With a simple adjustment of the reaction conditions,
      we were able to obtain either pure cis or trans acid. Optical resolution was
      accomplished via diastereomeric salt formation or alternatively via
      chromatography on a chiral stationary phase. Finally, ab initio calculations gave
      an explanation for the observed cis selectivity in the initial step. 

PMID- 23957680
TI  - The ability of S.aureus to form biofilm on the Ti-6Al-7Nb scaffolds produced by
      Selective Laser Melting and subjected to the different types of surface
      modifications.
AB  - The Gram-positive coccus, Staphylococcus aureus, is the leading etiologic agent
      of limb and life-threatening biofilm-related infections in the patients following
      the orthopaedic implantations. The aim of the present paper is to estimate the
      ability of S. aureus to form biofilm on titanium alloy (Ti-6Al-7Nb) scaffolds
      produced by Selective Laser Melting (SLM) and subjected to the different types of
      surface modifications, including ultrasonic cleaning and chemical polishing. The
      results obtained indicate significantly the decreased ability of S.aureus to form
      biofilm on the surface of scaffolds subjected to the chemical polishing in
      comparison to the scaffolds cleaned ultrasonically. The data provided can be
      useful for future applications of the SLM technology in production of Ti-6Al-7Nb
      medical implants.

PMID- 23957681
TI  - Ostreid herpesvirus 1 infection in farmed Pacific oyster larvae Crassostrea gigas
      (Thunberg) in Korea.

PMID- 23957682
TI  - Hypoxia-regulated gene expression and prognosis in loco-regional gastroesophageal
      cancer.
AB  - Gastroesophageal cancers are heterogeneous diseases with a poor outcome.
      Prognostic and predictive factors are needed to improve patient survival. Hypoxia
      is an adverse prognostic factor and is associated with resistance to chemo- and
      radiotherapy in various cancers. However, knowledge on the impact of hypoxia in
      gastroesophageal cancer is limited. The aim of this study was to evaluate
      potential prognostic factors in terms of a subset of hypoxia-responsive genes and
      clinicopathological parameters in patients with gastroesophageal cancer. MATERIAL
      AND METHODS: Ninety-five patients with loco-regional gastroesophageal cancer
      treated with curative intent were retrospectively analyzed. Based on formalin
      fixed paraffin-embedded diagnostic biopsies gene expressions of 15 hypoxia
      induced and pH-independent genes from a previously described hypoxia gene
      expression classifier was quantified. The prognostic impact was evaluated for
      overall survival (OS) and disease-specific survival (DSS). Uni- and multivariate
      Cox proportional hazards model was used to identify hypoxia-responsive gene
      expression and clinicopathological parameters as prognostic markers. RESULTS: An
      unsupervised hierarchical clustering of hypoxia regulated genes showed two well
      differentiated patient clusters: One cluster of tumors with high gene expression
      and another with low gene expression, indicating a more hypoxic genotype versus a
      less hypoxic genotype respectively. As the group of esophageal squamous cell
      carcinomas (ESCC) alone showed intra-group heterogeneity this group was ranked
      according to the gene expression of the 15 genes. The most hypoxic third showed a
      trend towards a poorer outcome in terms of OS [HR = 0.48 (CI 0.21-1.07), p =
      0.07] and DSS [HR = 0.48 (CI 0.18-1.24), p = 0.13]. Treatment response was
      identified as an independent prognostic factor for DSS in the group of ESCC [HR =
      0.21 (CI 0.05-0.95), p = 0.04]. CONCLUSION: Gene expression analysis of 15
      hypoxia-responsive genes was identified as a promising prognostic marker in
      patients with ESCC. Further studies confirming these results in larger patient
      cohorts are needed.

PMID- 23957683
TI  - Clinical impact of using the deterministic patient dose calculation algorithm
      Acuros XB for lung stereotactic body radiation therapy.
AB  - PURPOSE: To evaluate the clinical impact of using the deterministic dose
      calculation algorithm, Acuros XB, for early stage lung cancer patients undergoing
      stereotactic body radiotherapy (SBRT). MATERIAL AND METHODS: Seventy-seven stage
      I non-small cell lung cancer patients who underwent lung SBRT from 2008 to 2012
      at our center were included in this study. All treatment plans originally
      calculated by the anisotropic analytical algorithm (AAA) were recalculated using
      the AAA and Acuros XB algorithms with identical monitor units and beam
      arrangements. The dose, dose distribution, conformality number (CN) and
      heterogeneity index (HI) of the target were determined for each plan. A paired
      matched t-test was used to evaluate the difference between the mean dose, the
      dose distribution, and the CN and HI for the target. The importance of tumor
      (volume, location), patient (pulmonary functional, body mass index) and treatment
      (number of SBRT beams) on the dose distributions obtained from the two algorithms
      was statistically determined using linear regression analyses. RESULTS: The mean
      target dose was same for both algorithms. Compared to AAA, a small and
      significant difference in dose distribution in the target was found for the
      Acuros XB algorithm, resulting in lower conformity (-2.1%, p < 0.0001) and higher
      heterogeneity (p < 0.0001) of dose. Single logistic regression identified
      pulmonary function, number of beams and target location as being correlated with
      the difference of CN between the two calculations. Multivariate analysis
      indicated that the patient's pulmonary function (p = 0.0296) was the only
      predictor for the difference in conformality between the two dose calculation
      algorithms. CONCLUSIONS: In lung SBRT, the patient's pulmonary function is
      responsible for the difference in target dose distribution between the Acuros XB
      and AAA algorithms. The Acuros XB algorithm could be used to advantage in
      patients with compromised pulmonary function based on its accurate modeling of
      lung tissue in comparison to AAA.

PMID- 23957684
TI  - Dosimetric verification of complex radiotherapy with a 3D optically based
      dosimetry system: dose painting and target tracking.
AB  - BACKGROUND: The increasing complexity of radiotherapy (RT) has motivated research
      into three-dimensional (3D) dosimetry. In this study we investigate the use of 3D
      dosimetry with polymerizing gels and optical computed tomography (optical CT) as
      a verification tool for complex RT: dose painting and target tracking. MATERIALS
      AND METHODS: For the dose painting studies, two dosimeters were irradiated with a
      seven-field intensity modulated radiotherapy (IMRT) plan with and without dose
      prescription based on a hypoxia image dataset of a head and neck patient. In the
      tracking experiments, two dosimeters were irradiated with a volumetric modulated
      arc therapy (VMAT) plan with and without clinically measured prostate motion and
      a third with both motion and target tracking. To assess the performance, 3D gamma
      analyses were performed between measured and calculated stationary dose
      distributions. RESULTS: Gamma pass-rates of 95.3% and 97.3% were achieved for the
      standard and dose-painted IMRT plans. Gamma pass-rates of 91.4% and 54.4% were
      obtained for the stationary and moving dosimeter, respectively, while tracking
      increased the pass-rate for the moving dosimeter to 90.4%. CONCLUSIONS: This
      study has shown that the 3D dosimetry system can reproduce and thus verify
      complex dose distributions, also when influenced by motion.

PMID- 23957685
TI  - Pilot evaluation of web enabled symptom monitoring in cystic fibrosis.
AB  - BACKGROUND: People with cystic fibrosis (CF) frequently experience isolation and
      are subjected to extensive complex treatment regimens which could be complemented
      by remote support. In the current research this is particularly relevant as the
      location, Tasmania, has the second highest incidence of CF in the world. This
      paper provides an overview of the evaluation of a pilot trial of an information
      system conceptualised and developed to assist people with CF, and their families,
      to enhance their skills and communication in relation to self-management for
      their condition. METHODS: The pilot involved people with CF ranging in age from
      19 months to 52 years and their families. The primary outcome was the perceived
      usability of the online-symptom diary from the user's perspective. To assess
      perceived usability qualitative semi-structured interviews were conducted pre-
      and post-pilot and analysed using thematic coding. RESULTS: Participants
      initially and primarily perceived myCF as a system that would help others and
      enable peer support. Connectivity and involvement were highlighted as complex
      issues that needed consideration. CONCLUSION: There was an overall encouraging
      response to the pilot and indications that the use of information communication
      technology to complement health care delivery and facilitate self-care skills may
      be particularly suited to the Australian context where geographical distances and
      isolation provide a relative barrier to specialist care for chronic complex
      conditions.

PMID- 23957686
TI  - Revealing interdyad differences in naturally occurring staff reactions to
      challenging behaviour of clients with severe or profound intellectual
      disabilities by means of Clusterwise Hierarchical Classes Analysis (HICLAS).
AB  - BACKGROUND: Investigating interdyad (i.e. couples of a client and their usual
      caregiver) differences in naturally occurring patterns of staff reactions to
      challenging behaviour (e.g. self-injurious, stereotyped and
      aggressive/destructive behaviour) of clients with severe or profound intellectual
      disabilities is important to optimise client-staff interactions. Most studies,
      however, fail to combine a naturalistic setup with a person-level analysis, in
      that they do not involve a careful inspection of the interdyad differences and
      similarities. METHOD: In this study, the recently proposed Clusterwise
      Hierarchical Classes Analysis (HICLAS) method is adopted and applied to data of
      in which video fragments (recorded in a naturalistic setting) of a client showing
      challenging behaviour and the staff reacting to it were analysed. In a
      Clusterwise HICLAS analysis, the staff-client dyads are grouped into a number of
      clusters and the prototypical behaviour-reaction patterns that are specific for
      each cluster (i.e. interdyad differences and similarities) are revealed. RESULTS:
      Clusterwise HICLAS discloses clear interdyad differences (and similarities) in
      the prototypical patterns of clients' challenging behaviour and the associated
      staff reactions, complementing and qualifying the results of earlier studies in
      which only general patterns were disclosed. CONCLUSIONS: The usefulness and
      clinical relevance of Clusterwise HICLAS is demonstrated. In particular,
      Clusterwise HICLAS may capture idiosyncratic aspects of staff-client
      interactions, which may stimulate direct support workers to adopt person-centred
      support practices that take the specific abilities of the client into account.

PMID- 23957688
TI  - Resolving the assessment center construct validity problem (as we know it).
AB  - Ongoing concern about the construct validity of assessment center dimensions has
      focused on postexercise dimension ratings (PEDRs) that are consistently found to
      reflect exercise variance to a greater degree than dimension variance. Here, we
      present a solution to this problem. Based on the argument that PEDRs are an
      intermediate step toward an overall dimension rating, and that the overall
      dimension rating should be the focus of inquiry, we demonstrate that correlated
      sources of dimension variance accumulate and increasingly displace uncorrelated
      sources of both systematic variance and error. Viewing overall dimension ratings
      as a composite of PEDRs, we show dimension variance will commonly quickly
      overtake exercise-specific variance as the dominant source of variance as ratings
      from multiple exercises are combined. We embed our results in a new framework for
      categorizing different levels of construct variance dominance, and our results
      indicate that with as few as two exercises, dimension variance can reach our
      lowest level of construct variance dominance. However, the largest source of
      dimension variance is a general factor. We conclude that the construct validity
      problem in assessments centers never existed as historically framed, but the
      presence of a general factor may limit interpretation for developmental purposes.

PMID- 23957687
TI  - A field experiment: reducing interpersonal discrimination toward pregnant job
      applicants.
AB  - The current research targets 4 potential stereotypes driving hostile attitudes
      and discriminatory behaviors toward pregnant women: incompetence, lack of
      commitment, inflexibility, and need for accommodation. We tested the relative
      efficacy of reducing concerns related to each of the stereotypes in a field
      experiment in which female confederates who sometimes wore pregnancy prostheses
      applied for jobs in a retail setting. As expected, ratings from 3 perspectives
      (applicants, observers, and independent coders) converged to show that pregnant
      applicants received more interpersonal hostility than did nonpregnant applicants.
      However, when hiring managers received (vs. did not receive) counterstereotypic
      information about certain pregnancy-related stereotypes (particularly lack of
      commitment and inflexibility), managers displayed significantly less
      interpersonal discrimination. Explicit comparisons of counterstereotypic
      information shed light on the fact that certain information may be more effective
      in reducing discrimination than others. We conclude by discussing how the current
      research makes novel theoretical contributions and describe some practical
      organizational implications for understanding and improving the experiences of
      pregnant workers.

PMID- 23957689
TI  - Emotionally unskilled, unaware, and uninterested in learning more: reactions to
      feedback about deficits in emotional intelligence.
AB  - Despite the importance of self-awareness for managerial success, many
      organizational members hold overly optimistic views of their expertise and
      performance-a phenomenon particularly prevalent among those least skilled in a
      given domain. We examined whether this same pattern extends to appraisals of
      emotional intelligence (EI), a critical managerial competency. We also examined
      why this overoptimism tends to survive explicit feedback about performance.
      Across 3 studies involving professional students, we found that the least skilled
      had limited insight into deficits in their performance. Moreover, when given
      concrete feedback, low performers disparaged either the accuracy or the relevance
      of that feedback, depending on how expediently they could do so. Consequently,
      they expressed more reluctance than top performers to pursue various paths to
      self-improvement, including purchasing a book on EI or paying for professional
      coaching. Paradoxically, it was top performers who indicated a stronger desire to
      improve their EI following feedback.

PMID- 23957690
TI  - Controlling vibrational energy flow in liquid alkylbenzenes.
AB  - Ultrafast infrared (IR) Raman spectroscopy was used to study vibrational energy
      in phi-S alkylbenzenes, where phi = C6H5 and substituents S were CH3- (toluene),
      (CH3)2CH- (isopropylbenzene, IPB), or (CH3)3C- (t-butylbenzene, TBB). Using
      methods described previously,1 the normal modes were classified as phenyl (phi),
      substituent (S), or global (G). IR pulses were tuned to find conditions that
      maximized the localization of initial CH-stretch excitations on phi or S. Anti
      Stokes Raman spectroscopy measured transient energy content of Raman-active S,
      phi, and G modes, to determine the rates of phenyl to substituent (Phi -> S) or
      substituent to phenyl (S -> Phi) transfer during the first few picoseconds, when
      energy transfer was mainly intramolecular. Since phenyl CH-stretches were 90-130
      cm(-1) uphill in energy from substituent CH-stretches, of interest were S -> Phi
      processes where molecular structure and local couplings were more important than
      energy differences. The Phi -> S process efficiencies were small and about equal
      with all three substituents. The S -> Phi transfer efficiencies could be
      increased by increasing substituent size. This was opposite to what would be
      predicted on the basis of the larger density of states of larger substituents,
      and it provides a path toward controlling forward-to-backward vibrational energy
      transfer ratios. The S -> Phi transfer efficiency is understood as resulting from
      an increase in the local anharmonic couplings. A heavier substituent, when
      vibrating, transfers energy more effectively to the phenyl group. 

PMID- 23957691
TI  - Copper indium gallium selenide (CIGS) photovoltaic devices made using multistep
      selenization of nanocrystal films.
AB  - The power conversion efficiency of photovoltaic devices made with ink-deposited
      Cu(InxGa1-x)Se2 (CIGS) nanocrystal layers can be enhanced by sintering the
      nanocrystals with a high temperature selenization process. This process, however,
      can be challenging to control. Here, we report that ink deposition followed by
      annealing under inert gas and then selenization can provide better control over
      CIGS nanocrystal sintering and yield generally improved device efficiency.
      Annealing under argon at 525  degrees C removes organic ligands and diffuses
      sodium from the underlying soda lime glass into the Mo back contact to improve
      the rate and quality of nanocrystal sintering during selenization at 500  degrees
      C. Shorter selenization time alleviates excessive MoSe2 formation at the Mo back
      contact that leads to film delamination, which in turn enables multiple cycles of
      nanocrystal deposition and selenization to create thicker, more uniform absorber
      films. Devices with power conversion efficiency greater than 7% are fabricated
      using the multiple step nanocrystal deposition and sintering process. 

PMID- 23957692
TI  - Virulence in Pectobacterium atrosepticum is regulated by a coincidence circuit
      involving quorum sensing and the stress alarmone, (p)ppGpp.
AB  - Pectobacterium atrosepticum (Pca) is a Gram-negative phytopathogen which causes
      disease by secreting plant cell wall degrading exoenzymes (PCWDEs). Previous
      studies have shown that PCWDE production is regulated by (i) the intercellular
      quorum sensing (QS) signal molecule, 3-oxo-hexanoyl-l-homoserine lactone (OHHL),
      and (ii) the intracellular 'alarmone', (p)ppGpp, which reports on nutrient
      limitation. Here we show that these two signals form an integrated coincidence
      circuit which ensures that metabolically costly PCWDE synthesis does not occur
      unless the population is simultaneously quorate and nutrient limited. A (p)ppGpp
      null DeltarelADeltaspoT mutant was defective in both OHHL and PCWDE production,
      and nutritional supplementation of wild type cultures (which suppresses (p)ppGpp
      production) also suppressed OHHL and PCWDE production. There was a substantial
      overlap in the transcriptome of a (p)ppGpp deficient relA mutant and of a QS
      defective expI (OHHL synthase) mutant, especially with regards to virulence
      associated genes. Random transposon mutagenesis revealed that disruption of rsmA
      was sufficient to restore PCWDE production in the (p)ppGpp null strain. We found
      that the ratio of RsmA protein to its RNA antagonist, rsmB, was modulated
      independently by (p)ppGpp and QS. While QS predominantly controlled virulence by
      modulating RsmA levels, (p)ppGpp exerted regulation through the modulation of the
      RsmA antagonist, rsmB. 

PMID- 23957693
TI  - Multigenerational transmission of family size in contemporary Sweden.
AB  - The study of the intergenerational transmission of fertility has a long history
      in demography, but until now research has focused primarily on parents' influence
      on their children's fertility patterns and has largely overlooked the possible
      influence of other kin. This study examines the transmission of fertility
      patterns from parents, grandparents, uncles, and aunts, using event history
      models to determine the risk of first, second, and third births. Swedish register
      data are used to study the 1970-82 birth cohorts. The findings indicate strong
      associations between the fertility of index persons and that of their parents,
      and also independent associations between the completed fertility of index
      persons and that of their grandparents and parents' siblings. The results suggest
      that, when examining background effects in fertility research, it is relevant to
      take a multigenerational perspective and to consider the characteristics of
      extended kin. 

PMID- 23957694
TI  - Synthesis and structural characterization of hydrolysis products within the
      uranyl iminodiacetate and malate systems.
AB  - The interplay of hydrolysis and chelation by organic ligands results in the
      formation of novel uranium species in aqueous solutions. Many of these molecular
      complexes have been identified by spectroscopic and potentiometric techniques,
      but a detailed structural understanding of these species is lacking.
      Identification of possible uranyl hydrolysis products in the presence of organic
      functional groups has been achieved by the crystallization of molecular species
      into a solid-state compound, followed by structural and chemical characterization
      of the material. The structures of three novel molecular complexes containing
      either iminodiacetate (ida) (Na3[(UO2)3(OH)3(ida)3].8H2O (1)) or malate (mal)
      (K(pip)2[(UO2)3O(mal)3].6H2O (2a) (pip = C4N2H12), (2b)
      (pip)3[(UO2)3O(mal)3].H2O, and (pip)6[(UO2)11(O)4(OH)4(mal)6(CO3)2].23H2O (3))
      ligands have been determined by single-crystal X-ray diffraction and have been
      chemically characterized by IR, Raman, and NMR spectroscopies. A major structural
      component in compounds 1 and 2 is a trimeric 3:3 uranyl ida or mal species, but
      different bridging groups between the metal centers create variations in the
      structural topologies of the molecular units. Compound 3 contains a large
      polynuclear cluster with 11 U atoms, which is composed of trimeric and pentameric
      building units chelated by mal ligands and linked through hydroxyl groups and
      carbonate anions. The characterized compounds represent novel structural
      topologies for U(6+) hydrolysis products that may be important molecular species
      in near-neutral aqueous systems. 

PMID- 23957696
TI  - Current intravesical therapy for non-muscle invasive bladder cancer.
AB  - INTRODUCTION: Transurethral resection of the bladder tumour (TURBT) is still the
      standard initial treatment for non-muscle invasive bladder cancer (NMIBC).
      However, even after a radical resection, recurrence (30 - 80%) and progression (1
      - 45%) are commonly seen. Intravesical therapy provides direct contact of the
      agent with the bladder mucosa and clearly has improved the outcome, especially in
      high-risk disease. AREAS COVERED: The role of a good initial TURBT is emphasized.
      Risk assessment tools are discussed. Different intravesical therapies are
      enumerated according to the latest literature, with the emphasis on Bacillus
      Calmette-Guerin (BCG), including the discussion on the optimal dose and schedule.
      New developments are mentioned. EXPERT OPINION: A radical TURBT is essential for
      good prognosis. For optimal visualisation of tumours, fluorescence techniques
      should be used with low threshold, especially in case of suspicion of carcinoma
      in situ (CIS). Increased completeness of the resection will lead to less
      persisting disease and less need for adjuvant treatment. A re-TURBT should be
      done when in doubt of radical resection (judged by the pathologist or the
      surgeon). Risk assessment is essential, but the available tools are outdated. A
      single post-operative instillation (SPI) with chemotherapy is only indicated in
      low-risk disease. BCG is the treatment of choice for high-grade disease. BCG
      should be given as maintenance. Awareness of deterioration of the prognosis after
      progression is of great importance. In BCG failures, cystectomy should be
      strongly advised. Chemotherapy in combination with hyperthermia seems to be a new
      promising treatment.

PMID- 23957695
TI  - A process evaluation: does recruitment for an exercise program through ethnically
      specific channels and key figures contribute to its reach and receptivity in
      ethnic minority mothers?
AB  - BACKGROUND: Ethnic minority women from low-income countries who live in high
      income countries are more physically inactive than ethnic majority women in those
      countries. At the same time, they can be harder to reach with health promotion
      programs. Targeting recruitment channels and execution to ethnic groups could
      increase reach and receptivity to program participation. We explored using
      ethnically specific channels and key figures to reach Ghanaian, Antillean, and
      Surinamese mothers with an invitation for an exercise program, and subsequently,
      to determine the mothers' receptivity and participation. METHODS: We conducted a
      mixed methods process evaluation in Amsterdam, The Netherlands. To recruit
      mothers, we employed ethnically specific community organizations and ethnically
      matched key figures as recruiters over Dutch health educators. Reach and
      participation were measured using reply cards and the attendance records from the
      exercise programs. Observations were made of the recruitment process. We
      interviewed 14 key figures and 32 mothers to respond to the recruitment channel
      and recruiter used. Content analysis was used to analyze qualitative data.
      RESULTS: Recruitment through ethnically specific community channels was
      successful among Ghanaian mothers, but less so among Antillean and Surinamese
      mothers. The more close-knit an ethnic community was, retaining their own culture
      and having poorer comprehension of the Dutch language, the more likely we were to
      reach mothers through ethnically specific organizations. Furthermore, we found
      that using ethnically matched recruiters resulted in higher receptivity to the
      program and, among the Ghanaian mothers in particular, in greater participation.
      This was because the ethnically matched recruiter was a familiar, trusted person,
      a translator, and a motivator who was enthusiastic, encouraging, and able to
      adapt her message (targeting/tailoring). Using a health expert was preferred in
      order to increase the credibility and professionalism of the recruitment.
      CONCLUSIONS: Recruitment for an exercise program through ethnically specific
      organizations seems to contribute to its reach, particularly in close-knit,
      highly organized ethnic communities with limited fluency in the local language.
      Using ethnically matched recruiters as motivator, translator, and trusted person
      seems to enhance receptivity of a health promotion program. An expert is likely
      to be needed for effective information delivery.

PMID- 23957697
TI  - Synthesis and characterization of Pt(IV) fluorescein conjugates to investigate
      Pt(IV) intracellular transformations.
AB  - Pt(IV) anticancer compounds typically operate as prodrugs that are reduced in the
      hypoxic environment of cancer cells, losing two axial ligands in the process to
      generate active Pt(II) species. Here we report the synthesis of two fluorescent
      Pt(IV) prodrugs of cisplatin in order to image and evaluate the Pt(IV) reduction
      process in simulated and real biological environments. Treatment of the complexes
      dissolved in PBS buffer with reducing agents typically encountered in cells,
      glutathione or ascorbate, afforded a 3- to 5-fold fluorescence turn-on owing to
      reduction and loss of their fluorescein-based axial ligands, which are quenched
      when bound to platinum. Both Pt(IV) conjugates displayed moderate cytotoxicity
      against human cancer cell lines, with IC50 values higher than that of cisplatin.
      Immunoblotting and DNA flow cytometry analyses of one of the complexes,
      Pt(IV)FL2, revealed that it damages DNA, causes cell cycle arrest in S or G2/M
      depending on exposure time, and ultimately triggers apoptotic cell death.
      Fluorescence microscopic studies prove that Pt(IV)FL2 enters cells intact and
      undergoes reduction intracellularly. The results are best interpreted in terms of
      a model in which the axial fluorescein ligands are expelled through lysosomes,
      with the platinum(II) moiety generated in the process binding to genomic DNA,
      which results in cell death. 

PMID- 23957698
TI  - Association study of chemokine (C-C motif) ligand 5 gene polymorphism and
      papillary thyroid cancer.
AB  - The association between polymorphism of CC chemokine ligand 5 (CCL5) and cancer
      has been reported in several studies, however, there is no data in papillary
      thyroid cancer (PTC). OBJECTIVES: The aim of this study was to investigate
      whether a promoter single nucleotide polymorphisms (SNP) in CCL5 contributes to
      the development of PTC and assess the relationships between the CCL5 SNP and the
      cliniopathologic characteristics of PTC. METHODS: One promoter SNP (rs2107538, 
      281C/T) in CCL5 was genotyped using direct sequencing in 93 PTC patients and 212
      healthy controls. Genetic data were analyzed using SNPStats, Helixtree, and
      SNPAnalyzer. PTC patients were dichotomized and compared with respect to
      cliniopathologic characteristics of PTC. RESULTS: An association was evident
      between PTC and SNP (rs2107538) in CCL5 [codominant model 2 (T/T vs. C/C), OR =
      2.74, 95% CI = 1.18-6.37, p = .019; dominant model, OR = 2.25, 95% CI = 1.01
      5.03, p = .049; recessive model, OR = 1.73, 95% CI = 1.06-2.82, p = .030]. When
      the genetic relationships between SNP and subgroups of PTC patients were
      assessed, SNP rs2107538 in CCL5 was not associated with any clinicopathologic
      characteristics of PTC. CONCLUSIONS: SNP in the CCL5 -281 promoter gene could
      increase the risk of developing PTC in Koreans.

PMID- 23957699
TI  - NSE/alphaNAE positivity in B-lineage acute lymphoblastic leukemia: revisiting a
      potential cytochemical diagnostic pitfall.
AB  - Cytochemical staining for leukemia typing is declining in hematology
      laboratories, but the use of flow cytometry may not be possible in some settings.
      Aberrant cytochemical nonspecific esterase/alpha-naphthyl acetate esterase
      (NSE/alphaNAE) positive B-lymphoblasts can cause confusion with monoblasts, a
      potentially dangerous pitfall. This unusual cytochemical NSE/alphaNAE positivity
      had been associated with relatively poorer outcome of acute lymphoblastic
      leukemia (ALL) in the era prior to the advent of routine multicolor flow
      cytometric immunophenotyping. We reviewed morphological, cytochemical and flow
      cytometric data from five cases of B-lineage ALL that showed NSE/alphaNAE
      positivity and were diagnosed definitively using multi-parametric flow cytometric
      immunophenotypic analysis. Diffuse or dot-like (localized) strong cytochemical
      NSE/alphaNAE activity was detected in all cases and all showed one or more
      features of high risk disease. The number of NSE/alphaNAE positive blasts in the
      marrow varied from 10 to 75%. The morphological differential diagnoses included T
      lymphoid lineage ALL and acute monoblastic leukemia (AML-M5). Flow cytometric
      data revealed B-lineage antigens and the absence of monocytic or other myeloid
      markers resolved the diagnosis. These cases underscore the importance of
      immunophenotyping in all cases of suspected ALL regardless of the cytochemical
      findings. Although the numbers are small, the association with high risk disease
      observed in all five of our cases may corroborate the previously reported poor
      prognostic value of such aberrant cytochemical staining.

PMID- 23957700
TI  - Expression of CA IX in dysplasia adjacent to surgical resection margins of oral
      squamous cell carcinoma.
AB  - Carbonic anhydrase (CA) IX is a hypoxia marker located almost exclusively in
      tumor cells. We analyzed the expression of this marker in dysplastic lesions
      adjacent to the surgical resection margin in patients with oral squamous cell
      carcinoma. We investigated 70 archived tumors, 36 of which showed dysplasia
      adjacent to the surgical margin. We used tissue microarray technology to perform
      an immunohistochemical study of CA IX expression. We found 12 (33.3%) cases of
      mild dysplasia (10 negative, 2 positive for CA IX), five (13.9%) cases of
      moderate dysplasia (3 negative, 2 positive for CA IX), 1 (2.8%) case of severe
      dysplasia (negative for CA IX) and 18 (50%) cases of carcinoma in situ (10
      negative, 8 positive for CA IX). In cases of intense expression of CA IX in the
      tumor, the same distribution of positive and negative cases was observed in all
      degrees of dysplasia (mild, moderate, severe), although cases of carcinoma in
      situ tended to be CA IX positive.

PMID- 23957701
TI  - Histochemical detection of steroid synthesizing cells in the testes of goldfish,
      Carassius auratus, during the annual reproductive cycle.
AB  - We investigated the sites of Delta(5)-3beta-hydroxysteroid dehydrogenase (3 beta
      HSD) and glucose-6-phosphate dehydrogenase (G-6-PD) synthesis in the testes of
      goldfish, Carassius auratus, during the annual reproductive cycle. The
      histochemistry of fish gonads has been investigated previously in many species
      other than goldfish. The reproductive cycle of goldfish, is divided into five
      stages and the steroid synthesizing cells of the testes were studied during these
      stages, using histochemical techniques. We found that interstitial cells and
      seminiferous tubules are the main steroid synthesizing sites in testes of
      goldfish, and that enzyme activity was more intense in the interstitial cells
      than in the seminiferous tubules. During the pre-spawning months, 3 beta-HSD and
      G-6-PD activities were weak compared to the spawning months.

PMID- 23957702
TI  - Histochemistry: historical development and current use in pathology.
AB  - We describe the history of the histochemical stains that contributed most to the
      development of modern pathology during the last two centuries. Histochemical
      stains are presented in a list, which provides the essential information about
      year, country and main use of each to enable the reader to follow the
      chronological and geographical history of histochemistry. In addition to the
      historical evaluation of histochemistry development, we investigate how many
      classical histochemical stains survive in a modern laboratory of pathology and
      how often they are used for diagnostic practice compared to immunohistochemical
      (IHC) techniques. A ratio of about one histochemical reaction to 13 IHC reactions
      was tabulated. Finally, our data make it possible to define different cultural
      approaches to the terminology of histochemical and IHC stains: the former were
      based on eponyms, which link the stain with the name of its inventor, while the
      latter use a more impersonal biological terminology.

PMID- 23957703
TI  - Immunohistochemical expressions of adropin and inducible nitric oxide synthase in
      renal tissues of rats with streptozotocin-induced experimental diabetes.
AB  - Diabetes is characterized by high blood glucose levels; it occurs in 30-35% of
      the population. Elevated glucose levels can damage a number of organs, including
      the kidneys. Several peptide hormones participate in maintaining glucose
      homeostasis including the recently discovered "adropin," a 42 amino acid peptide
      hormone. Adropin also alters inducible nitric oxide synthase (iNOS) expression.
      Therefore, we studied how adropin and iNOS expression is altered in the renal
      tissues of streptozotocin (STZ) induced diabetic rats. Seven sham, seven control
      and seven Wistar albino male rats were fed standard rat pellets and water ad
      libitum for 10 weeks. The rats in the diabetic group were injected i.p. with a
      single dose of 60 mg/kg STZ dissolved in 0.1 M phosphate-citrate buffer, pH 4.5.
      After the 10-week experimental period, the rats in both groups were anesthetized
      and decapitated. Kidney tissues were excised and placed in 10% formaldehyde
      solution, taken through routine histological procedures, and embedded in
      paraffin. Sections 5-6 MUm thick were stained immunohistochemically using the
      avidin-biotin complex (ABC) method. Adropin and iNOS immunoreactivity were co
      localized in the glomeruli, peritubular interstitial cells and peritubular
      capillary endothelium of the cortex; the thin limb of the loop of Henle in the
      medulla; and medullary peritubular interstitial cells and endothelium of the
      peritubular capillaries in both the control and diabetic groups. The intensities
      of adropin and iNOS immunoreactivity increased with the severity of the diabetes.
      Intense adropin immunoreactivity was detected in both the smooth muscle and human
      small intestine Paneth cells that were used as positive controls. The elevated
      levels of adropin and iNOS in the kidney indicates that these substances are
      involved in the pathophysiology of diabetes; this constitutes a compensatory
      mechanism against the damage inflicted by the disease.

PMID- 23957704
TI  - Expressions and localizations of Bax/Bcl-2 proteins during metamorphosis of
      Pelophylax ridibundus.
AB  - Bcl-2 and Bax proteins are expressed in cells of the tails of Pelophylax
      ridibundus larvae. We investigated the levels of these proteins in tails
      undergoing apoptosis. Apoptotic cells were observed in the epidermis, muscle and
      notochord of tails of different lengths. The apoptotic cells in epidermis
      exhibited the typical features of apoptosis. Amorphous masses and irregularities
      in striated muscle tissue undergoing apoptosis and apoptotic remnants in the
      notochord also were observed. In general, Bax staining in the epidermis,
      subepidermal fibroblast layer, muscle and notochord cells increased, while Bcl-2
      staining decreased as the tail regressed. Our results suggest that during tail
      regression due to metamorphosis, Bcl-2 and Bax proteins play key roles in the
      apoptosis of tail epidermis, subepidermal fibroblast layer, muscle and notochord
      cells.

PMID- 23957705
TI  - Salusin-alpha and -beta expression in heart and aorta with and without metabolic
      syndrome.
AB  - Metabolic syndrome (MetS) is a major health problem throughout the world. The
      role of salusins has not been investigated in heart and aortic tissues under MetS
      conditions. We examined the distribution of salusin alpha (sal-alpha) and salusin
      beta (sal-beta) immunoreactivity in heart and aortic tissues and measured
      circulating salusin concentrations, glucose, insulin, triglycerides, free fatty
      acids, uric acid, and total cholesterol in Sprague-Dawley rats with and without
      MetS. Lipid, glucose, insulin and uric acid levels were determined using an
      autoanalyzer. Serum and tissue salusin levels were measured using ELISA. The
      expressions of salusins in the heart and aorta tissues were determined using
      immunohistochemical methods. Serum high density lipoprotein cholesterol (HDL-C),
      sal-alpha and sal-beta concentrations were significantly lower in the MetS group
      than in the control group. Low density lipoprotein cholesterol (LDL-C), very low
      density lipoprotein cholesterol (VLDL-C), total cholesterol, glucose, uric acid
      and insulin concentrations were higher in the MetS group than in the control
      group. Sal-alpha and sal-beta were synthesized locally in the fibroblasts and
      smooth muscle cells of the media of the aorta and in the muscle cells of the
      heart. Local synthesis of sal-alpha and sal-beta was decreased with MetS. Our
      findings indicate that decreased serum concentrations of salusins and HDL-C and
      increased uric acid, glucose and triglyceride concentrations may be indicators of
      MetS and could play a role in the development of cardiovascular disease.

PMID- 23957706
TI  - Quirks of dye nomenclature. 1. Evans blue.
AB  - The history, origin, identity, chemistry and use of Evans blue dye are described
      along with the first application to staining by Herbert McLean Evans in 1914. In
      the 1930s, the dye was marketed under the name, Evans blue dye, which was
      profoundly more acceptable than the ponderous chemical name.

PMID- 23957707
TI  - Evaluation of yield of currently available diagnostics by sample type to optimize
      detection of respiratory pathogens in patients with a community-acquired
      pneumonia.
AB  - BACKGROUND: For the detection of respiratory pathogens, the sampling strategy may
      influence the diagnostic yield. Ideally, samples from the lower respiratory tract
      are collected, but they are difficult to obtain. OBJECTIVES: In this study, we
      compared the diagnostic yield in sputum and oropharyngeal samples (OPS) for the
      detection of respiratory pathogens in patients with community-acquired pneumonia
      (CAP), with the objective to optimize our diagnostic testing algorithm. METHODS:
      Matched sputum samples, OPS, blood cultures, serum, and urine samples were taken
      from patients (>18 years) with CAP and tested for the presence of possible
      respiratory pathogens using bacterial cultures, PCR for 17 viruses and five
      bacteria and urinary antigen testing. RESULTS: When using only conventional
      methods, that is, blood cultures, sputum culture, urinary antigen tests, a
      pathogen was detected in 49.6% of patients (n = 57). Adding molecular detection
      assays increased the yield to 80%. A pathogen was detected in 77 of the 115
      patients in OPS or sputum samples by PCR. The sensitivity of the OPS was lower
      than that of the sputum samples (57% versus 74%). In particular, bacterial
      pathogens were more often detected in sputum samples. The sensitivity of OPS for
      the detection of most viruses was higher than in sputum samples (72% versus 66%),
      except for human rhinovirus and respiratory syncytial virus. CONCLUSION: Addition
      of PCR on both OPS and sputum samples significantly increased the diagnostic
      yield. For molecular detection of bacterial pathogens, a sputum sample is
      imperative, but for detection of most viral pathogens, an OPS is sufficient.

PMID- 23957708
TI  - Fibrin sealant patch for repair of acute type a aortic dissection.
AB  - INTRODUCTION: The use of glues to repair disrupted tissue during acute type-A
      aortic dissection (TAD) surgery may be discontinuous, and cause embolization and
      cell necrosis. We report a method of fibrin sealant patch (FSP) to reinforce
      dissected aortic tissue with a collagen double layer coated with
      fibrinogen/thrombin on either side (TachoSil(r); Takeda, Konstanz, Germany).
      METHODS: In 12 patients (seven male, 66.9 +/- 11.7 years) with acute TAD we
      performed FSP of the intima-media disruption at the proximal and distal
      anastomosis of the aorta. We analyzed the perioperative course and
      echocardiographical, radiological, and clinical outcomes up to one year.
      Additionally, we investigated the adhesive potential of the FSP in vitro.
      RESULTS: In vitro, the adhesive strength of the FSP was 60 N/cm(2). In-hospital
      mortality was 8.3% (n = 1), recovery was satisfactory with no major neurologic
      events, mean ICU stay was 13.6 +/- 6.0 days, mean hospital stay was 20.7 +/- 4.4
      days. A total of 7.0 +/- 2.6 RBC, 3.4 +/- 1.5 platelets, and 8.0 +/- 4.3 FFP were
      transfused. One-year survival was 83.3%. In 6/6 DeBakey II dissections the
      intimal tear was completely resected, in 2/6 DeBakey I dissections the false
      lumen in the descending aorta completely collapsed. No redissections and no
      relevant aortic valve insufficiencies were seen during follow-up. CONCLUSION:
      This analysis shows that FSP using a collagen matrix double layer coated with
      fibrinogen/thrombin is feasible, safe, and effective in repairing the dissected
      aortic tissue. It results in continuous reinforcement of aortic tissue and
      completely avoids the need for conventional glues.

PMID- 23957709
TI  - The root transcriptome for North American ginseng assembled and profiled across
      seasonal development.
AB  - BACKGROUND: Ginseng including North American ginseng (Panax quinquefolius L.) is
      one of the most widely used medicinal plants. Its success is thought to be due to
      a diverse collection of ginsenosides that serve as its major bioactive compounds.
      However, few genomic resources exist and the details concerning its various
      biosynthetic pathways remain poorly understood. As the root is the primary tissue
      harvested commercially for ginsenosides, next generation sequencing was applied
      to the characterization and assembly of the root transcriptome throughout
      seasonal development. Transcripts showing homology to ginsenoside biosynthesis
      enzymes were profiled in greater detail. RESULTS: RNA extracts from root samples
      from seven development stages of North American ginseng were subjected to 454
      sequencing, filtered for quality and used in the de novo assembly of a collective
      root reference transcriptome consisting of 41,623 transcripts. Annotation efforts
      using a number of public databases resulted in detailed annotation information
      for 34,801 (84%) transcripts. In addition, 3,955 genes were assigned to metabolic
      pathways using the Kyoto Encyclopedia of Genes and Genomes. Among our results, we
      found all of the known enzymes involved in the ginsenoside backbone biosynthesis
      and used co-expression analysis to identify a number of candidate sequences
      involved in the latter stages ginsenoside biosynthesis pathway. Transcript
      profiles suggest ginsenoside biosynthesis occurs at distinct stages of
      development. CONCLUSIONS: The assembly generated provides a comprehensive
      annotated reference for future transcriptomic study of North American ginseng. A
      collection of putative ginsenoside biosynthesis genes were identified and
      candidate genes predicted from the lesser understood downstream stages of
      biosynthesis. Transcript expression profiles across seasonal development suggest
      a primary dammarane-type ginsenoside biosynthesis occurs just prior to plant
      senescence, with secondary ginsenoside production occurring throughout
      development. Data from the study provide a valuable resource for conducting
      future ginsenoside biosynthesis research in this important medicinal plant.

PMID- 23957710
TI  - Drug-induced acute pancreatitis: results from the hospital-based Berlin case
      control surveillance study of 102 cases.
AB  - BACKGROUND: Drug toxicity is a well-known cause of acute pancreatitis (AP).
      Although many drugs have been associated with AP, the magnitude of the risk of
      most of them remains largely unknown. AIM: To determine the pancreatotoxic risk
      of a wide range of drugs. METHODS: The hospital-based Berlin case-control
      surveillance study, including all 51 Berlin hospitals in a hospital network,
      ascertained 102 cases with idiopathic AP (IAP) and 750 controls between 2002 and
      2011. Patients with IAP were thoroughly validated using anamnestic, clinical or
      laboratory data. Drug exposure was obtained in a face-to-face interview. Possible
      drug aetiology was assessed in individual patients through a standardised
      causality assessment applying the criteria of the World Health Organization. Drug
      risks were further quantified [odds ratios (OR) with 95% confidence intervals
      (CI)] in a case-control design with unconditional logistic regression analysis.
      RESULTS: The pancreatotoxic risk of several drugs, including azathioprine (OR
      5.1; 95% CI 1.9-13.5), fenofibrate (OR 12.2; 95% CI 2.3-69.1), mesalazine (OR
      3.3; 95% CI 1.1-9.5) or angiotensin-converting enzyme inhibitors, was
      corroborated by case-control analysis and causality assessment. Causality
      assessment suggested a pancreatotoxic potential, among others, for mercaptopurine
      or the seldom reported leflunomide, and alluded to a novel risk for tocilizumab.
      Case-control analysis showed an increased risk for two phytotherapeutics:
      harpagophytum and valerian radix. CONCLUSIONS: Our study quantified the
      pancreatotoxic risk of different drugs and phytotherapeutics. The findings
      corroborate previous results from the literature but also indicate risks for
      substances not previously reported, highlighting the need for further controlled
      studies on pancreatic toxicity.

PMID- 23957712
TI  - Copper-catalyzed synthesis of benzo[b]thiophenes and benzothiazoles using
      thiocarboxylic acids as a coupling partner.
AB  - An efficient copper-catalyzed approach to benzo[b]thiophene and benzothiazole
      derivatives using thiocarboxylic acids as a sulfur source has been developed. In
      the presence of CuI and 1,10-phen, and n-Pr3N as the base, (2
      iodobenzyl)triphenylphosphonium bromide and (2
      iodophenylimino)triphenylphosphorane reacted smoothly with thiocarboxylic acids
      to give benzo[b]thiophene and benzothiazole derivatives in good yields via
      sequential Ullmann-type C-S bond coupling and Wittig condensation. 

PMID- 23957713
TI  - Tree species as a potential source of bio-herbicides for controlling Parthenium
      hysterophorus L.
AB  - To assess the herbicidal potential of Eugenia jambolana Lam., Ricinus communis
      L., Ziziphus jujuba L. and Ziziphus mauritiana L. against noxious weed Parthenium
      hysterophorus L., germination bioassay using their 1%, 2%, 3%, 4% and 5% (w/v)
      and seedling growth bioassay using their 5% (w/v) (on dry weight basis) aqueous
      leaf extracts (ALE) were conducted. ALE of R. communis showed maximum reductions
      in germination percentage (79%), germination index (89%) and seedling biomass
      (88%) as well as maximum delays in mean germination time (211%) and time to 50%
      germination (265%) of parthenium whereas maximum reductions in its seedling
      length (47%) and seedling vigour index (97%) were shown by Z. mauritiana.
      Reciprocal dose-response relationship by probit regression analysis revealed that
      LC50 values of R. communis and Z. mauritiana are 1.04% and 1.44%, respectively.
      Therefore, R. communis and Z. mauritiana are potential sources of bio-herbicides
      against this weed.

PMID- 23957711
TI  - Facile synthesis of unsymmetrical acridines and phenazines by a Rh(III)-catalyzed
      amination/cyclization/aromatization cascade.
AB  - We report formal [3 + 3] annulations of aromatic azides with aromatic imines and
      azobenzenes to give acridines and phenazines, respectively. These transformations
      proceed through a cascade process of Rh(III)-catalyzed amination followed by
      intramolecular electrophilic aromatic substitution and aromatization. Acridines
      can be directly prepared from aromatic aldehydes by in situ imine formation using
      catalytic benzylamine. 

PMID- 23957714
TI  - Multicentre clinical trials' data management: a hybrid solution to exploit the
      strengths of electronic data capture and electronic health records systems.
AB  - BACKGROUND: Clinical Trials (CTs) are indispensable instruments for evidence
      based medicine and frequently necessitate the management, sharing and analysis of
      large amounts of data amongst partners in different locations. METHODS: To
      effectively satisfy these requirements, the proposed solution combines a web
      platform and a Clinical Data Management System (CDMS) to exploit the strengths of
      Electronic Health Records (EHR) and Electronic Data Capture (EDC) systems. The
      core of the proposal is a relational database which has high data structuring
      characteristics and utilises biomedical controlled vocabularies (e.g. LOINC and
      ICD). In addition, units and normality ranges were collected for data comparison
      through the application of the Z-score transformation. RESULTS: The obtained CDMS
      preserves the EDC's flexibility and user autonomy and permits the creation of
      patient cohorts, as in the EHR. Accordingly, clinical information, after the
      initial recording, is available for different simultaneous multicentre CTs.
      Furthermore, interface runtime controls guarantee high data quality during data
      entering processes. Currently, the proposed system has been developed in the HIV
      and eye diseases fields in Italy. CONCLUSIONS: The proposed solution is flexible
      and suitable to perform multicentre research within a varying range of medical
      domains. In the future, the automatic importation of information from hospitals
      has been planned through an HL7 standard interface which would improve both data
      quantity and quality.

PMID- 23957715
TI  - Outcome of patients with HER2-positive breast cancer treated with or without
      adjuvant trastuzumab in the Finland Capecitabine Trial (FinXX).
AB  - BACKGROUND: Little information is available about survival outcomes of patients
      with HER2-positive early breast cancer treated with adjuvant capecitabine
      containing chemotherapy with or without trastuzumab. PATIENTS AND METHODS: One
      thousand and five hundred patients with early breast cancer were entered to the
      Finland Capecitabine trial (FinXX) between January 2004 and May 2007, and were
      randomly assigned to receive either three cycles of adjuvant TX (docetaxel,
      capecitabine) followed by three cycles of CEX (cyclophosphamide, epirubicin,
      capecitabine; TX-CEX) or three cycles of docetaxel followed by three cycles of
      CEF (cyclophosphamide, epirubicin, fluorouracil; T-CEF). The primary endpoint was
      recurrence-free survival (RFS). The study protocol was amended in May 2005 while
      study accrual was ongoing to allow adjuvant trastuzumab for patients with HER2
      positive cancer. Of the 284 patients with HER2-positive cancer accrued to FinXX,
      176 (62.0%) received trastuzumab after amending the study protocol, 131 for 12
      months and 45 for nine weeks. The median follow-up time was 6.7 years. RESULTS:
      Patients with HER2-positive cancer who received trastuzumab had better RFS than
      those who did not (five-year RFS 89.2% vs. 75.9%; HR 0.41, 95% CI 0.23-0.72; p =
      0.001). Patients treated with trastuzumab for 12 months or nine weeks had similar
      RFS. There was no significant interaction between trastuzumab administration and
      the type of chemotherapy. Four (2.3%) patients treated with trastuzumab had heart
      failure or left ventricular dysfunction, three of these received capecitabine.
      CONCLUSION: Adjuvant trastuzumab improves RFS of patients treated with TX-CEX or
      T-CEF. Few patients had cardiac failure.

PMID- 23957716
TI  - Safety and efficacy of aerobic training in operable breast cancer patients
      receiving neoadjuvant chemotherapy: a phase II randomized trial.
AB  - BACKGROUND: To evaluate the safety and efficacy of moderate-to-high intensity
      aerobic training in breast cancer patients receiving neoadjuvant chemotherapy.
      METHODS: Twenty patients with stage IIB-IIIC operable breast cancer were randomly
      assigned to receive doxorubicin plus cyclophosphamide (AC) or AC in combination
      with aerobic training (AC + AET) (n = 10/group) for 12 weeks. The AC+ AET group
      performed three supervised aerobic cycle ergometry sessions per week at 60%-100%
      of exercise capacity (VO2peak). Safety outcomes included exercise testing as well
      as treatment- and exercise training-related adverse events (AEs), whereas
      efficacy outcomes included cardiopulmonary function and patient-reported outcomes
      (PROs) as measured by a cardiopulmonary exercise test (CPET) and Functional
      Assessment of Cancer Therapy-Breast (FACT-B) scale. RESULTS: Twelve non
      significant ECG abnormalities and three non-life threatening events occurred
      during CPET procedures. One AE was reported during aerobic training. There were
      no significant between group differences for clinician-documented events (e.g.
      pain, nausea) or hematological parameters (p's > 0.05). Attendance and adherence
      rates to aerobic training were 82% and 66%, respectively. Intention-to-treat
      analysis indicated that VO2peak increased by 2.6 +/- 3.5 ml/kg/min (+ 13.3%) in
      the AC + AET group and decreased by 1.5 +/- 2.2 ml/kg/min (-8.6%) in the AC group
      (between group difference, p = 0.001). FACT-B increased 11.1 points in the AC +
      AET group compared to a 1.5 point decrease in the AC group (between group
      difference, p = 0.685). CONCLUSION: Moderate-to-high intensity aerobic training
      when conducted with one-on-one supervision is a safe adjunct therapy associated
      with improvements in cardiopulmonary function and select PROs during neoadjuvant
      chemotherapy.

PMID- 23957717
TI  - In vitro cultivation model for Heterosporis saurida (Microsporidia) isolated from
      lizardfish, Saurida undosquamis (Richardson).
AB  - Heterosporis saurida is a microsporidian that infects lizardfish, Saurida
      undosquamis (Richardson, 1848), in the Arabian Sea. Spores were isolated from
      infected lizardfish and used to infect derived fish cell lines: common carp brain
      (CCB), epithelioma papulosum cyprinid (EPC), fathead minnow epithelial (FHM),
      rainbow trout gonad (RTG), bluegill fry (BF-2) and chinook salmon embryo (CHSE).
      Non-fish cell lines were also tested that include: insect (SF-9), rabbit (RK-13)
      and African green monkey (Vero E6). No growth of H. saurida was observed in any
      fish cell line, SF-9 or Vero E6 cell lines. H. saurida spores grew only in RK-13
      cell line and were detected by immunofluorescence. Developmental stages of H.
      saurida were seen in RK-13 cells by light and transmission electron microscopy,
      and species identification was confirmed by sequencing. This study demonstrated
      that H. saurida was able to proliferate in the mammalian RK-13 cell line, which
      thus represents an in vitro model for conducting molecular genetics and cell
      pathogen interaction studies of Heterosporis. 

PMID- 23957718
TI  - A novel factor V mutation causes a normal activated protein C ratio despite the
      presence of a heterozygous F5 R506Q (factor V Leiden) mutation.

PMID- 23957719
TI  - Emotion dysregulation and social competence: stability, change and predictive
      power.
AB  - BACKGROUND: Social difficulties are closely linked to emotion dysregulation among
      children with typical development (TD). Children with developmental delays (DD)
      are at risk for poor social outcomes, but the relationship between social and
      emotional development within this population is not well understood. The current
      study examines the extent to which emotion dysregulation is related to social
      problems across middle childhood among children with TD or DD. METHOD: Children
      with TD (IQ >= 85, n = 113) and children with DD (IQ <= 75, n = 61) participated
      in a longitudinal study. Annual assessments were completed at ages 7, 8 and 9
      years. At each assessment, mothers reported on children's emotion dysregulation,
      and both mothers and teachers reported on children's social difficulties.
      RESULTS: Children with DD had higher levels of emotion dysregulation and social
      problems at each age than those with TD. Emotion dysregulation and social
      problems were significantly positively correlated within both TD and DD groups
      using mother report of social problems, and within the TD group using teacher
      report of social problems. Among children with TD, emotion dysregulation
      consistently predicted change in social problems from one year to the next.
      However, among children with DD, emotion dysregulation offered no unique
      prediction value above and beyond current social problems. CONCLUSIONS: Results
      suggested that the influence of emotion regulation abilities on social
      development may be a less salient pathway for children with DD. These children
      may have more influences, beyond emotion regulation, on their social behaviour,
      highlighting the importance of directly targeting social skill deficits among
      children with DD in order to ameliorate their social difficulties.

PMID- 23957720
TI  - Interprofessional competence: a qualitative exploration of social work and
      nursing students' experience.
AB  - Being a professional in today's health care system carries with it an expectation
      of becoming interprofessional. This study was designed to explore the perceived
      development of the participants' interprofessional competence through
      interprofessional seminars and collaborative community practice. Data were
      collected from social work and nursing undergraduates through two
      interprofessional seminar discussions, followed by focus group interviews after
      the completion of 2 weeks of practice experience. Study findings included: (a)
      role clarification and enhancement, (b) evolving role emphasis, (c) understanding
      the importance of and various communications in teamwork, and (d) being more
      responsive to the meaning of teamwork and the understanding of collaborative
      interdependence. Through interprofessional collaborative practice, students
      developed an insight into teamwork, where they witnessed the merits of
      collaboration and gained an understanding of each other's lack of holistic
      approach. In addition, not only the particular practice settings but also the
      role variations involved revealed various dimensions of interprofessional
      learning.

PMID- 23957721
TI  - A high content assay to assess cellular fitness.
AB  - A universal process in experimental biology is the use of engineered cells; more
      often, stably or transiently transfected cells are generated for the purpose.
      Therefore, it is important that cell health assessment is conducted to check for
      stress mediated by induction of heat shock proteins (Hsps). For this purpose, we
      have developed an integrated platform that would enable a direct assessment of
      transfection efficiency (TE) combined with cellular toxicity and stress response.
      We make use of automated microscopy and high content analysis to extract from the
      same well a multiplexed readout to assess and determine optimal chemical
      transfection conditions. As a proof of concept, we investigated seven commercial
      reagents, in a matrix of dose and time, to study transfection of an EGFP DNA
      plasmid into HeLa cells and their consequences on health and fitness; where we
      scored for cellular proliferation, EGFP positive cells, and induction of Hsp10
      and Hsp70 as makers of stress responses. FuGENE HD emerged as the most optimal
      reagent with no apparent side effects suitable for performing microtiter based
      miniaturized transfection for both chemical and RNAi screening. In summary, we
      report on a high content assay method to assess cellular overall fitness upon
      chemical transfection. 

PMID- 23957722
TI  - Characterizing visual performance in mice: an objective and automated system
      based on the optokinetic reflex.
AB  - Testing optokinetic head or eye movements is an established method to determine
      visual performance of laboratory animals, including chickens, guinea pigs, mice,
      or fish. It is based on the optokinetic reflex which causes the animals to track
      a drifting stripe pattern with eye and head movements. We have developed an
      improved version of the optomotor test with better control over the stimulus
      parameters, as well as a high degree of automation. The stripe pattern is
      presented on computer monitors surrounding the animal. By tracking the head
      position of freely moving animals in real time, the visual angle under which the
      stripes of the pattern appeared was kept constant even for changing head
      positions. Furthermore, an algorithm was developed for automated evaluation of
      the tracking performance of the animal. Comparing the automatically determined
      behavioral score with manual assessment of the animals' tracking behavior
      confirmed the reliability of our methodology. As an example, we reproduced the
      known contrast sensitivity function of wild type mice. Furthermore, the
      progressive decline in visual performance of a mouse model of retinal
      degeneration, rd10, was demonstrated.

PMID- 23957723
TI  - Novel 1,2,4-thiadiazole derivatives: crystal structure, conformational analysis,
      hydrogen bond networks, calculations, and thermodynamic characteristics of
      crystal lattices.
AB  - The results of X-ray crystallographic and computational studies of twelve 1,2,4
      thiadiazole derivatives are reported. The effect of orientation of different
      parts of the molecules on crystal organization and hydrogen bond network were
      studied. DFT calculations were carried out in order to explore conformational
      preferences of the molecules inside and outside of crystal environment. The role
      of hydrogen bonds was found to be essential for the stabilization of
      conformationally strained molecules as well as for the packing density of such
      molecules in a crystal. Thermodynamic aspects of sublimation processes of the
      studied compounds were analyzed using temperature dependencies of their vapor
      pressure. Thermophysical characteristics of the molecular crystals were obtained
      and compared with the sublimation enthalpy and the structural parameters. The
      influence of crystal structure features on the sublimation enthalpy and on the
      melting temperature was analyzed. 

PMID- 23957724
TI  - Micropatterned stretchable circuit and strain sensor fabricated by lithography on
      an electrospun nanofiber mat.
AB  - This paper describes a novel approach for composite nanofiber mats and its
      application to fabricate a strain sensor. Electrospun poly(4-vinylpyridine)
      (P4VP) nanofiber mats are micropatterned by a lithographic approach that includes
      selective oxidation of the nanofibers and removal of unreacted fibers. The
      P4VP/HAuCl4 complex is converted to P4VP/Au composites by chemical reduction. We
      investigate the electrical resistivity of the composite mats according to the
      number of complexation-and-reduction cycles, the thickness of the fiber mats, and
      the annealing temperatures which control the percolation of the Au nanoparticles
      in the fiber mats. Nozzle printing of a polymeric solution on the patterned
      nanofiber mats simply produces an array of strain-sensitive and strain-invariant
      units. The patterns demonstrate high strain-sensing performance without any
      mechanical and electrical failure over 200 bending cycles in the strain range of
      epsilon<0.17.

PMID- 23957725
TI  - Broadening the scope of research on emotion regulation strategies and
      psychopathology.
AB  - Despite the increasing interest in the study of emotion regulation strategies and
      psychopathology, researchers have predominantly focused on covert emotion
      regulation strategies-that is, those strategies that occur within the individual
      (e.g., cognitive reappraisal, suppression). Conversely, less attention has been
      devoted to the examination of the relationship between psychopathology and overt
      emotion regulation strategies (e.g., drinking alcohol, seeking advice). This has
      resulted in a limited understanding of the complex repertoire of emotion
      regulation strategies that individuals possess, and how patterns in the use of
      strategies might relate to psychopathology. We asked 218 undergraduates to report
      on their habitual use of 15 covert and overt emotion regulation strategies and
      symptoms of seven different mental disorders. Overt strategies were associated
      with symptoms and, at times, they predicted psychopathology above and beyond the
      more frequently studied covert strategies. These findings have implications for
      developing a more sophisticated understanding of patterns of adaptive and
      maladaptive emotion regulation.

PMID- 23957726
TI  - Nonporous titanium-oxo molecular clusters that reversibly and selectively adsorb
      carbon dioxide.
AB  - Nonporous titanium(IV) clusters supported by carboxylate ligands show selective
      sorption of carbon dioxide even in the amorphous phase. A ring-type Ti8 cluster
      with a permanent inner pore also adsorbs gases, but not selectively. 

PMID- 23957727
TI  - No correlation between slip reduction in low-grade spondylolisthesis or change in
      neuroforaminal morphology and clinical outcome.
AB  - BACKGROUND: In instrumented posterolateral fusion reduction of a
      spondylolisthesis is appealing on theoretical grounds since this may lead to
      indirect decompression of the entrapped nerve roots. However, there is no
      consensus in the literature whether a beneficial effect of reduction on outcome
      can be expected. The objective of the current study was to evaluate whether a
      correlation between the extent of listhesis reduction and clinical improvement
      could be established. METHODS: From two ongoing prospective studies 72 patients
      with a single-level instrumented posterolateral lumbar fusion for low-grade
      spondylolisthesis (isthmic/degenerative 51/21) were evaluated. Radiographs and
      clinical outcome scores were available at baseline, 6 weeks and 1 year after
      surgery. Changes in neuroforaminal morphology were measured on calibrated
      radiographs. These changes in radiographic parameters were correlated to clinical
      outcome (Visual Analogue Score (VAS) leg pain, Oswestry Disability Index (ODI)).
      Fusion status was assessed on Computed Tomography-scan at one year. RESULTS: A
      mean spondylolisthesis of 25 percent was reduced to 15 percent at 6 weeks with
      some loss of reduction to 17 percent at one year. The VAS and ODI significantly
      improved at both time intervals after surgery (p < 0.001). No significant
      correlations could be established between the extent of slip reduction and
      improvement in VAS or ODI (Pearson's correlation -0.2 and 0.07 respectively at
      one year); this also accounted for the other radiographic parameters. A fusion
      rate of 64 percent was seen on CT-scan. CONCLUSIONS: Clinical outcome was not
      related to the obtained radiographic reduction of the slipped vertebra in
      patients with a lumbar fusion for low grade spondylolisthesis. Loss of reduction
      or non-union on CT-scans had no effect on the clinical outcome. Reduction of a
      low-grade spondylolisthesis in spinal fusion is appealing, however, there is no
      evidence that it positively affects clinical outcome on the short term. TRIAL
      REGISTRATION: ISRCTN43648350.

PMID- 23957729
TI  - The effect of levosimendan in rat mesenteric ischemia/reperfusion injury.
AB  - BACKGROUND: Intestinal ischemia reperfusion (IR) is associated with morbidity and
      mortality. We first examined the role of levosimendan in the protection of
      intestine after mesenteric IR. METHODS: The rats were divided into six groups:
      (1) Control group; (2) Levosimendan group; (3) Ischemia group (60 min of
      occlusion); (4) IR group (60 min of occlusion and then 60 min reperfusion); (5)
      IR + 1 mg/kg levosimendan group: Levosimendan was given intraperitonally 30 min
      prior to the ischemia; (6) IR + 2 mg/kg levosimendan group. RESULTS: The levels
      of TNF-alpha, IL-6, and IL-1beta were found to have increased in the IR group.
      The serum levels of TNF-alpha, IL-6, and IL-1beta were found to have decreased as
      a result of the administration of both doses of levosimendan in the IR. Relative
      TNF-alpha and NFkappaB mRNA levels was decreased by administration of both doses
      of levosimendan in the IR. SOD activity and GSH levels for IR group were lower
      than, and 8-ISO levels were higher than, those of the sham-operated rat and
      ischemia alone group. CONCLUSIONS: Both doses of levosimendan had preventive
      effects on the alterations that occurred in the intestinal tissues after IR.
      Levosimendan administration attenuated in reperfusion injury of intestine and
      consequently protects intestinal mucosa and oxidant-antioxidant balance of ileum.

PMID- 23957728
TI  - Synthesis of polymer-lipid nanoparticles for image-guided delivery of dual
      modality therapy.
AB  - For advanced treatment of diseases such as cancer, multicomponent,
      multifunctional nanoparticles hold great promise. In the current study we report
      the synthesis of a complex nanoparticle (NP) system with dual drug loading as
      well as diagnostic properties. To that aim we present a methodology where
      chemically modified poly(lactic-co-glycolic) acid (PLGA) polymer is formulated
      into a polymer-lipid NP that contains a cytotoxic drug doxorubicin (DOX) in the
      polymeric core and an anti-angiogenic drug sorafenib (SRF) in the lipidic corona.
      The NP core also contains gold nanocrystals (AuNCs) for imaging purposes and
      cyclodextrin molecules to maximize the DOX encapsulation in the NP core. In
      addition, a near-infrared (NIR) Cy7 dye was incorporated in the coating. To
      fabricate the NP we used a microfluidics-based technique that offers unique NP
      synthesis conditions, which allowed for encapsulation and fine-tuning of optimal
      ratios of all the NP components. NP phantoms could be visualized with computed
      tomography (CT) and near-infrared (NIR) fluorescence imaging. We observed timed
      release of the encapsulated drugs, with fast release of the corona drug SRF and
      delayed release of a core drug DOX. In tumor bearing mice intravenously
      administered NPs were found to accumulate at the tumor site by fluorescence
      imaging. 

PMID- 23957730
TI  - Comparison of volunteers' experience of using, and accuracy of reading, different
      types of home pregnancy test formats.
AB  - BACKGROUND: Women suspecting pregnancy need an accurate result when they conduct
      a home pregnancy test. A variety of tests are available from simple professional
      style strips to midstream tests with a digitally displayed result. However, it is
      not known whether all these formats can be used and read correctly by untrained
      women. OBJECTIVES: The aim of this study is to evaluate usability and reading
      accuracy of home pregnancy test formats. METHODS: Female volunteers, 18 - 45
      years (Manchester, UK) completed questionnaires on their home-use experience of
      six pregnancy tests (strip, cassette, midstream visual and digital formats).
      These volunteers then evaluated device results using hCG-urine standards at a
      study centre, thereafter completing a questionnaire and ranking evaluation.
      RESULTS: Data were available from 111 volunteers. Women preferred midstream test
      formats; > 70% scored branded midstream digital and easy-use visual tests as 1or
      2 (7-point Likert score), compared with ~ 30% for store-brand and branded
      midstream visual tests, and < 10% for cassette or strip tests. Many cassette
      tests (23%) failed to provide a result (4, <= 2% for strips, midstream,
      respectively). Volunteers disagreed with study co-ordinator reading of test
      results in 30 and 40% of cases for the cassette and strip test results,
      respectively, compared with < 3% when using midstream digital or easy-use visual
      tests. Volunteers preferred the branded midstream digital, followed by branded
      midstream easy-use and visual tests. CONCLUSIONS: In this study, the branded
      midstream digital test was superior to other tests evaluated and fulfilled the
      criteria of being an easy-to-use and interpret test; strip and cassette tests
      showed poor performance in women's hands.

PMID- 23957731
TI  - Performance of a French sample on the French translation of the BNI screen for
      higher cerebral functions.
AB  - OBJECTIVE: To obtain normative data using a French translation of the BNI Screen
      for Higher Cerebral Functions (BNIS) administered to French-speaking individuals.
      METHODS: Recruitment and administration of the BNIS to a convenience sample of
      167 French-speaking individuals between the ages of 15-84 years. RESULTS: Mean
      BNIS total score for a French sample was within 1 point of what was observed in
      the original standardization study using 200 English-speaking controls. Age and
      education correlated significantly with BNIS scores in a manner reported by other
      studies. CONCLUSION: The French translation of the BNIS appears to be a reliable
      method of assessing higher cerebral functioning in French-speaking individuals.

PMID- 23957732
TI  - Obesity as a risk factor for severe influenza-like illness.
AB  - BACKGROUND: Obesity was recognized as in independent risk factor for influenza
      during the 2009 H1N1 influenza pandemic. OBJECTIVES: We evaluated the association
      between body mass index (BMI) and influenza-like illness (ILI) during two non
      pandemic influenza seasons (2003-2004 and 2004-2005) and during the spring and
      fall waves of the 2009 H1N1 pandemic. METHODS: Adults with severe (inpatient) and
      mild (outpatient) ILI were compared to those without ILI using a case-cohort
      design. The study was nested among those insured by a single health insurance
      company, receiving care from a large multispecialty practice. Data were collected
      from insurance claims and the electronic health record. The primary exposure was
      obesity (BMI >= 30.0 kg/m(2) ). RESULTS: Across three seasons, the crude and
      adjusted ORs for obesity and severe ILI were 1.65 (95% CI 1.31, 2.08) and 1.23
      (95% CI 0.97, 1.57), respectively. An association was observed for those aged 20
      59 years (adjusted OR 1.92, 95% CI 1.26, 2.90), but not for those 60 and older
      (adjusted OR 1.08, 95% CI 0.80, 1.46). The adjusted ORs for obesity and severe
      ILI in 2003-2004, 2004-2005, and during H1N1 were 1.14 (95% CI 0.80, 1.64), 1.24
      (95% CI 0.86, 1.79), and 1.76 (95% CI 0.91, 3.42), respectively. Among those with
      a Charlson Comorbidity Index score of zero, the adjusted ORs for 2003-2004, 2004
      2005, and H1N1 were 1.60 (95% CI 0.93, 2.76), 1.43 (95% CI 0.80, 2.56), and 1.90
      (95% CI 0.68, 5.27), respectively. CONCLUSIONS: Our results suggest a small to
      moderate association between obesity and hospitalized ILI among adults.

PMID- 23957733
TI  - Fine mapping of V(D)J recombinase mediated rearrangements in human lymphoid
      malignancies.
AB  - BACKGROUND: Lymphocytes achieve diversity in antigen recognition in part by
      rearranging genomic DNA at loci encoding antibodies and cell surface receptors.
      The process, termed V(D)J recombination, juxtaposes modular coding sequences for
      antigen binding. Erroneous recombination events causing chromosomal
      translocations are recognized causes of lymphoid malignancies. Here we show a
      hybridization based method for sequence enrichment can be used to efficiently and
      selectively capture genomic DNA adjacent to V(D)J recombination breakpoints for
      massively parallel sequencing. The approach obviates the need for PCR
      amplification of recombined sequences. RESULTS: Using tailored informatics
      analyses to resolve alignment and assembly issues in these repetitive regions, we
      were able to detect numerous recombination events across a panel of cancer cell
      lines and primary lymphoid tumors, and an EBV transformed lymphoblast line. With
      reassembly, breakpoints could be defined to single base pair resolution. The
      observed events consist of canonical V(D)J or V-J rearrangements, non-canonical
      rearrangements, and putatively oncogenic reciprocal chromosome translocations. We
      validated non-canonical and chromosome translocation junctions by PCR and Sanger
      sequencing. The translocations involved the MYC and BCL-2 loci, and activation of
      these was consistent with histopathologic features of the respective B-cell
      tumors. We also show an impressive prevalence of novel erroneous V-V
      recombination events at sites not incorporated with other downstream coding
      segments. CONCLUSIONS: Our results demonstrate the ability of next generation
      sequencing to describe human V(D)J recombinase activity and provide a scalable
      means to chronicle off-target, unexpressed, and non-amplifiable recombinations
      occurring in the development of lymphoid cancers.

PMID- 23957734
TI  - Randomised clinical trial: mesalazine and/or probiotics in maintaining remission
      of symptomatic uncomplicated diverticular disease--a double-blind, randomised,
      placebo-controlled study.
AB  - BACKGROUND: Placebo-controlled studies in maintaining remission of symptomatic
      uncomplicated diverticular disease (SUDD) of the colon are lacking. AIM: To
      assess the effectiveness of mesalazine and/or probiotics in maintaining remission
      in SUDD. METHODS: A multicentre, double-blind, placebo-controlled study was
      conducted. Two hundred and ten patients were randomly enrolled in a double-blind
      fashion in four groups: Group M (active mesalazine 1.6 g/day plus Lactobacillus
      casei subsp. DG placebo), Group L (active Lactobacillus casei subsp. DG 24
      billion/day plus mesalazine placebo), Group LM (active Lactobacillus casei subsp.
      DG 24 billion/day plus active mesalazine), Group P (Lactobacillus casei subsp. DG
      placebo plus mesalazine placebo). Patients received treatment for 10 days/month
      for 12 months. Recurrence of SUDD was defined as the reappearance of abdominal
      pain during follow-up, scored as >=5 (0: best; 10: worst) for at least 24
      consecutive hours. RESULTS: Recurrence of SUDD occurred in no (0%) patient in
      group LM, in 7 (13.7%) patients in group M, in 8 (14.5%) patients in group L and
      in 23 (46.0%) patients in group P (LM group vs. M group, P = 0.015; LM group vs.
      L group, P = 0.011; LM group vs. P group, P = 0.000; M group vs. P group, P =
      0.000; L group vs. P group, P = 0.000). Acute diverticulitis occurred in six
      group P cases and in one group L case (P = 0.003). CONCLUSION: Both cyclic
      mesalazine and Lactobacillus casei subsp. DG treatments, particularly when given
      in combination, appear to be better than placebo for maintaining remission of
      symptomatic uncomplicated diverticular disease. (ClinicalTrials.gov:
      NCT01534754).

PMID- 23957735
TI  - Global protein profiling reveals anti-EGFR monoclonal antibody 806-modulated
      proteins in A431 tumor xenografts.
AB  - An important mediator of tumorigenesis, the epidermal growth factor receptor
      (EGFR) is expressed in almost all non-transformed cell types, associated with
      tumor progression, angiogenesis and metastasis. The significance of the EGFR as a
      cancer therapeutic target is underscored by the clinical development of several
      different classes of EGFR antagonists, including monoclonal antibodies (mAb) and
      tyrosine kinase inhibitors. Extensive preclinical studies have demonstrated the
      anti-tumor effects of mAb806 against tumor xenografts overexpressing EGFR. EGF
      stimulation of A431 cells induces rapid tyrosine phosphorylation of intracellular
      signalling proteins which regulate cell proliferation and apoptosis. Detailed
      understanding of the intracellular signalling pathways and components modulated
      by mAbs (such as mAb806) to EGFR, and other growth factor receptors, remain
      limited. The use of fluorescence 2D difference gel electrophoresis (2D DIGE),
      coupled with sensitive MS-based protein profiling in A431 tumor (epidermoid
      carcinoma) xenografts, in combination with mAb806, revealed proteins modulating
      endocytosis, cell architecture, apoptosis, cell signalling pathways and cell
      cycle regulation, including Dynamin-1-like protein, cofilin-1 protein, and 14-3-3
      protein zeta/delta. Further, we report various proteins, including Interferon
      induced protein 53 (IFI53), and Oncogene EMS1 (EMS1) which have roles in the
      tumor microenvironment, regulating cancer cell invasiveness, angiogenesis and
      formation of metastases. These findings contribute to understanding the
      underlying biological processes associated with mAb806 therapy of EGFR-positive
      tumors, and identifying further potential protein markers that may contribute in
      assessment of the treatment response.

PMID- 23957736
TI  - Stereocontrolled synthesis of 1,2- and 1,3-diamine building blocks from aziridine
      aldehyde dimers.
AB  - Vicinal aziridine-containing diamines have been obtained with high syn
      stereoselectivity from readily available aziridine aldehyde dimers in the Petasis
      borono-Mannich reaction. Subsequent solvent- and/or nucleophile-dependent ring
      opening of the aziridine ring yields functionalized 1,2- and 1,3-diamines with
      high regioselectivity. The ring opening is also influenced by the substitution at
      the C3 position of the aziridine. A mechanistic rationale for the highly syn
      selective three-component reaction is proposed. 

PMID- 23957737
TI  - Mastication induced retrobulbar hemorrhage.
AB  - Retrobulbar hemorrhage is a feared potentially sight threatening complication
      after orbital decompression surgery. We present a patient, 36 hours after
      surgery, while forcefully biting, suddenly developed a retrobulbar hemorrhage
      arising from the temporalis muscle causing an orbital compartment syndrome. Rapid
      intervention with canthotomy and cantholysis was associated with recovery of
      vision from absent light perception to 20/20. A mastication induced retrobulbar
      hemorrhage has not been previously described.

PMID- 23957738
TI  - Experimental Lactococcus garvieae infection in rainbow trout, Oncorhynchus
      mykiss, Walbaum 1792: a comparative histopathological and immunohistochemical
      study.
AB  - The aim of this study was to induce Lactococcus garvieae infection in young and
      adult fish through different routes [intraperitoneal (IP) and immersion (IM)] and
      to investigate the pathogenesis and histopathological and immunohistochemical
      findings comparatively. For this purpose, a total of 180 rainbow trout (90 young,
      20 +/- 5 g and 90 adult, 80 +/- 10 g) obtained from a commercial fish farm were
      used. The fish were divided into eight groups, four experimental groups (Young
      Adult IP groups and Young-Adult IM groups, each contain 30 fish) and four control
      groups (Young-Adult IP Control groups and Young-Adult IM control groups, each
      contain 15 fishes). The experimental study was conducted using L. garvieae, and
      confirmatory identification was performed by PCR. The sequence result of the PCR
      amplicon of 16S rDNA from isolate L. garvieae LAC1 was determined and deposited
      in the GenBank database under accession number KC883976. Fish in the IP groups
      were intraperitoneally administered an inoculate containing 10(6) cfu mL(-1)
      bacteria 0.1 mL. In the IM groups, fish were kept in inoculated water containing
      10(8) cfu mL(-1) bacteria for 20 min. Mortality as well as clinical and
      pathological findings was recorded daily, and significant differences in
      macroscopic and microscopic results were observed between the IP and IM
      administration groups. All tissue samples were immunohistochemically stained by
      the avidin-biotin-peroxidase complex and immunofluorescence (IF) methods using
      polyclonal antibody to detect L. garvieae antigens. In immunoperoxidase staining
      in the IP groups, positive reactions to bacterial antigens were most commonly
      seen in the spleen, kidney, heart, liver, peritoneum and swim bladder. In the IM
      groups, bacterial antigens were most commonly found in the eye, gill, spleen and
      kidney. In the IF method, the distribution of antigens in tissue and organs was
      similar to the reactions with immunoperoxidase staining. Finally, in this
      experimental study, an important correlation was seen between the distribution of
      L. garvieae antigens and lesions developing in many organ and tissues.

PMID- 23957739
TI  - Integrated information visualization to support decision making for use of
      antibiotics in intensive care: design and usability evaluation.
AB  - Overuse of antibiotics is a critical problem in intensive care today. The
      situation is further complicated by the extremely data-intensive environment with
      clinical data presented in distributed, often stand-alone information systems. To
      access and interpret all data is a complex and time-consuming technical and
      cognitive challenge. We propose a holistic integrated visualization in the form
      of a patient overview to support physicians in decision making for use of
      antibiotics at intensive care units. Special emphasis is put on analysis of work
      processes to identify information needs, the development of a visualization tool
      based on an integrated data model, and usability testing of the tool in
      combination with an eye-tracking technology. The visualization tool was highly
      rated in terms of user performance and preferences, and the analysis of users'
      visual patterns showed that different types of data visualization may benefit
      specialist and resident intensive care physicians depending on the task to be
      performed. A highly interactive tool for integrated information visualization
      could potentially increase the understanding of a patient's infection status and
      ultimately enhance decision making for the use of antibiotics. 

PMID- 23957741
TI  - Why do adult dogs (Canis familiaris) commit the A-not-B search error?
AB  - It has been recently reported that adult domestic dogs, like human infants, tend
      to commit perseverative search errors; that is, they select the previously
      rewarded empty location in Piagetian A-not-B search task because of the
      experimenter's ostensive communicative cues. There is, however, an ongoing debate
      over whether these findings reveal that dogs can use the human ostensive
      referential communication as a source of information or the phenomenon can be
      accounted for by "more simple" explanations like insufficient attention and
      learning based on local enhancement. In 2 experiments the authors systematically
      manipulated the type of human cueing (communicative or noncommunicative) adjacent
      to the A hiding place during both the A and B trials. Results highlight 3
      important aspects of the dogs' A-not-B error: (a) search errors are influenced to
      a certain extent by dogs' motivation to retrieve the toy object; (b) human
      communicative and noncommunicative signals have different error-inducing effects;
      and (3) communicative signals presented at the A hiding place during the B trials
      but not during the A trials play a crucial role in inducing the A-not-B error and
      it can be induced even without demonstrating repeated hiding events at location
      A. These findings further confirm the notion that perseverative search error, at
      least partially, reflects a "ready-to-obey" attitude in the dog rather than
      insufficient attention and/or working memory.

PMID- 23957740
TI  - Animal metacognition: a tale of two comparative psychologies.
AB  - A growing literature considers whether animals have capacities that are akin to
      human metacognition (i.e., humans' capacity to monitor their states of
      uncertainty and knowing). Comparative psychologists have approached this question
      by testing a dolphin, pigeons, rats, monkeys, and apes using perception, memory,
      and food-concealment paradigms. As part of this consideration, some associative
      modelers have attempted to describe animals' "metacognitive" performances in low
      level, associative terms-an important goal if achievable. The authors summarize
      the empirical and theoretical situation regarding these associative descriptions.
      The associative descriptions in the animal-metacognition literature fail to
      encompass important phenomena. The sharp focus on abstract, mathematical
      associative models creates serious interpretative problems. The authors compare
      these failed associative descriptions with an alternative theoretical approach
      within contemporary comparative psychology. The alternative approach has the
      potential to strengthen comparative psychology as an empirical science and
      integrate it more fully within the mainstream of experimental psychology and
      cognitive science.

PMID- 23957742
TI  - Song learning in male and female Uraeginthus cyanocephalus, a tropical songbird
      species [corrected].
AB  - [Correction Notice: An Erratum for this article was reported in Vol 127(4) of
      Journal of Comparative Psychology (see record 2013-35936-001). In the article,
      the title of the article included parenthesis due to an editing error. The title
      should have been "Song Learning in Male and Female Uraeginthus Cyanocephalus, a
      Tropical Songbird Species." All versions of this article have been corrected.]
      Birdsong is a model in a wide range of research areas. Because of a research bias
      toward species with male-only song production, sex-specific differences in vocal
      learning processes have been neglected. We conducted an experimentally controlled
      song-learning study in the laboratory using blue-capped cordon-bleus (Uraeginthus
      cyanocephalus), an estrildid species with male and female song production. Adult
      males have larger syllable-type repertoires than females, which might require
      that males learn from males and females from females in order to develop
      appropriate sex-specific repertoire sizes. Young birds were housed together with
      different adult tutors during the song development and with another same age,
      same- or different-sex juvenile. Although only few birds imitated the song of
      adults, we detected song learning from same- and opposite-sex adult tutors. Males
      imitated songs of adult tutors more accurately than females. We found no evidence
      for song learning before Day 23. We detected sensory learning from adults
      (separated from the young by a wire mesh) after Day 40 in males but not in
      females. This might be due to sex-specific differences in the duration of the
      sensory acquisition phase (shorter in females) or the selectivity to social
      settings of song learning (higher in females, as they did not accept tutoring
      through a wire mesh). The song of young birds raised together converged on each
      other, suggesting an influence of the song of peer on the song development. This
      study provides a first step in understanding song learning in male and female
      cordon-bleus.

PMID- 23957744
TI  - Graphene in ionic liquids: collective van der Waals interaction and hindrance of
      self-assembly pathway.
AB  - Over the past decade, there has been much controversy regarding the microscopic
      mechanism by which the pi-electron-rich carbon nanomaterials such as graphene and
      carbon nanotubes can be dispersed in ionic liquids. Through a combination of a
      quantum mechanical calculation on the level of density functional theory, an
      extensive molecular dynamics study on the time scale of microseconds, and a
      kinetic analysis at the experimental time scale, we have demonstrated that
      collective van der Waals forces between ionic liquids and graphene are able to
      describe both the short-ranged cation-pi interaction and the long-ranged
      dispersion interaction and this microscopic interaction drives two graphene
      plates trapped in their metastable state while two graphene plates easily self
      assemble into graphite in water. 

PMID- 23957746
TI  - Fate of a giant {Mo72Fe30}-type polyoxometalate cluster in an aqueous solution at
      higher temperature: understanding related Keplerate chemistry, from molecule to
      material.
AB  - When the giant icosahedral {Mo72Fe30} cluster containing compound
      [Mo72Fe30O252(CH3COO)12{Mo2O7(H2O)}2{H2Mo2O8(H2O)}(H2O)91].150H2O (1) is refluxed
      in water for 36 h, it results in the formation of nanoiron molybdate, Fe2(MoO4)3,
      in the form of a yellow precipitate; this simple approach not only generates
      nanoferric molybdate at a moderate temperature but also helps to understand the
      stability of {Mo72Fe30} in terms of the linker-pentagon complementary
      relationship. 

PMID- 23957745
TI  - Glucagon-like peptide-1 receptor agonist administration suppresses both water and
      saline intake in rats.
AB  - Glucagon-like peptide-1 (GLP-1) plays an important role in energy homeostasis.
      Injections of GLP-1 receptor (GLP-1R) agonists suppress food intake, and
      endogenous GLP-1 is released when nutrients enter the gut. There is also growing
      evidence that the GLP-1 system is involved in the regulation of body fluid
      homeostasis. GLP-1R agonists suppress water intake independent of their effects
      on food intake. It is unknown, however, whether this suppressive effect of GLP-1R
      agonists extends to saline intake. Accordingly, we tested the effect of the GLP
      1R agonists liraglutide (0.05 MUg) and exendin-4 (0.05 MUg) on water and saline
      intake, as stimulated either by angiotensin II (AngII) or by water deprivation
      with partial rehydration (WD-PR). Each agonist suppressed AngII-induced water
      intake; however, only exendin-4 suppressed saline intake. WD-PR-induced water and
      saline intakes were both attenuated by each agonist. Analysis of drinking
      microstructure after WD-PR found a reliable effect of the agonists on burst
      number. Furthermore, exendin-4 conditioned a robust taste avoidance to
      saccharine; however, there was no similar effect of liraglutide. To evaluate the
      relevance of the conditioned taste avoidance, we tested whether inducing visceral
      malaise by injection of lithium chloride (LiCl) suppressed fluid intake.
      Injection of LiCl did not suppress water or saline intakes. Overall, these
      results indicate that the fluid intake suppression by GLP-1R activation is not
      selective to water intake, is a function of post-ingestive feedback, and is not
      secondary to visceral malaise. 

PMID- 23957747
TI  - Connecting family needs and TBI caregiver mental health in Mexico City, Mexico.
AB  - PURPOSE: This study examined relationships between caregiver mental health and
      the extent to which needs were met in families of individuals with traumatic
      brain injury (TBI) in Mexico City, Mexico. METHOD: Sixty-eight TBI caregivers
      completed Spanish versions of instruments assessing their own mental health and
      whether specific family needs were met. RESULTS: Twenty-seven per cent of
      caregivers reported clinically significant depression levels, 40% reported below
      average life satisfaction and 49% reported mild-to-severe burden. Several of the
      most frequently met family needs were in the emotional support domain, whereas
      the majority of unmet needs were in the health information domain. Family needs
      and caregiver mental health were significantly and highly related. When family
      needs were met, caregiver mental health was better. The strongest pattern of
      connections in multivariate analyses was between family instrumental support
      (assistance in the completion of daily life tasks) and caregiver burden, such
      that caregivers with less instrumental support had greater burden. Additional
      results suggested that instrumental support uniquely predicted caregiver
      satisfaction with life, burden and depression. CONCLUSIONS: Interventions for TBI
      caregivers, especially in Latin America, should help family members determine how
      best to meet their health information and instrumental needs, with the former
      being likely to improve caregiver mental health.

PMID- 23957748
TI  - Facile fabrication of hierarchical TiO2 nanobelt/ZnO nanorod heterogeneous
      nanostructure: an efficient photoanode for water splitting.
AB  - The TiO2 nanobelt/ZnO nanorod composite photoelectrodes with flower-like and/or
      grass-like microstructures have been fabricated via a facile solution growth
      routine, just by controlling the treatment of the TiO2 nanobelt substrate. For
      the flower-like composite, the ZnO nanorods disperse orientationally on TiO2
      nanobelt films, while for the grass-like one, ZnO nanorods grow disorderly like
      grass on the TiO2 nanobelt film surface. Furthermore, quasi-Fermi energy level
      changes of both photoelectrodes have been quantitatively characterized by the
      surface photovoltage based on the Kelvin probe, which clearly reveals the
      efficiency of photogenerated electron-hole separation. Owing to the decrease of
      quasi-Fermi energy level, the flower-like TiO2 nanobelt/ZnO nanorod heterogeneous
      nanostructure presents a high efficiency of photogenerated electron-hole
      separation. Therefore, the flower-like TiO2 nanobelt/ZnO nanorod heterogeneous
      nanostructure photoelectrode has achieved a better performance of water splitting
      compared with the grass-like TiO2 nanobelt/ZnO nanorod one. 

PMID- 23957749
TI  - One-session treatment for specific phobias: a review of Ost's single-session
      exposure with children and adolescents.
AB  - The purpose of this brief paper is to review the current status of one-session
      treatment (OST) for specific phobias in children and adolescents. Following a
      brief historical overview and description of OST, we systematically describe
      eight studies that have examined its efficacy in children and adolescents aged
      between 7 and17 years. We also explore phobia subtypes, age, gender, and
      comorbidity as possible moderators of treatment outcome. Studies have been
      conducted in Australia, Austria, the Netherlands, the USA, and Sweden. Although
      there is limited evidence that OST works better for animal phobias than other
      subtypes of phobias and for girls than boys, across studies there is considerable
      evidence that it is generally effective across phobia subtypes and for both boys
      and girls. No age differences in outcomes were noted, nor were any differences
      noted due to comorbidity. OST was found to be equally effective with children and
      adolescents with co-occurring multiple phobias and other anxiety disorders.
      Moreover, in at least one study, it was found to reduce untreated phobic and
      anxiety disorders in addition to the treated phobias. It is concluded that OST is
      a highly effective intervention for the treatment of specific phobias in children
      and adolescents. 

PMID- 23957750
TI  - Pediatric preoperative blood ordering: when is a type and screen or crossmatch
      really needed?
AB  - BACKGROUND: Unnecessary testing for and ordering of blood products adds to
      overall healthcare costs. OBJECTIVES: Determine intraoperative red blood cell
      (RBC) product utilization for pediatric procedures and costs associated with
      perioperative testing and ordering. METHODS: A retrospective chart review
      captured perioperative blood testing and intraoperative transfusion data for
      patients <19 years of age who underwent noncardiac surgery over a 13-month period
      at one tertiary care hospital. The main outcome measure was cost associated with
      testing for blood products in patients undergoing procedures that had a zero rate
      of transfusion. RESULTS: The intraoperative transfusion rate for 8620 noncardiac
      pediatric procedures was 2.78%. Of 8380 nontransfused patients, 707 (8.4%) had
      type and screen, and of those, 420 (5%) were crossmatched for RBC products in
      preparation for surgery. The 10 surgical procedures that had the highest
      perioperative blood testing but no instances of transfusion were as follows:
      colostomy or ileostomy takedown, spinal cord untethering, tunneled catheter
      placement, laparoscopic Nissen fundoplication, elbow reduction and fixation,
      lumbar puncture, suboccipital craniectomy, hip arthrogram, percutaneous
      intravascular central line, and tonsillectomy and adenoidectomy. Procedures with
      low transfusion probability and high crossmatch testing were ventriculoperitoneal
      shunt revision and growing rod distraction. For all nontransfused patients, the
      cost of obtaining type and screen was $31,815, and the cost for crossmatch was
      $25,200. CONCLUSION: Patients may undergo preoperative type and screen or
      crossmatch for procedures rarely associated with transfusion. Historic
      transfusion probability may be used to predict need for transfusion for specific
      surgical procedures and reduce unnecessary perioperative testing and associated
      costs.

PMID- 23957751
TI  - The preventive effect of dopamine infusion in rats with abdominal compartment
      syndrome.
AB  - BACKGROUND: The most significant perfusion disorder of the intra-abdominal
      viscera occurs in the abdominal compartment syndrome (ACS). Free oxygen radicals
      diffuse into the body during the reperfusion phase of ACS. Our aim was to
      determine the effects of dopamine infusion (3 MUg/kg/min) on renal perfusion,
      cytokine levels, free oxygen radicals, and renal histopathological changes in the
      presence of ACS in a prospective randomized manner. METHODS: Twenty-four male
      Sprague-Dawley rats were randomly divided into four groups (n = 6). Group 1 was
      used as control. In group 2, air was inflated until the intra-abdominal pressure
      (IAP) reached 20 mmHg. In group 3, dopamine was infused for 60 min meanwhile IAP
      was kept at 20 mmHg. In group 4, dopamine was infused for 60 min before IAP rise.
      After this phase, renal artery (RA) perfusion was measured continuously.
      Myeloperoxidase activity (MPO), glutathione (GSH), and lipid peroxidation (MDA)
      levels were measured in tissue samples and histopathological scoring was
      performed. RESULTS: Dopamine treatment before and during ACS significantly
      decreased MPO and MDA levels and also increased renal blood flow and GSH levels.
      However, histopathological damage was improved simultaneously. CONCLUSION:
      Dopamine infusion before and during ACS, increases renal perfusion and decreases
      free oxygen radicals. According to our findings, dopamine infusion may be
      proposed for the treatment of ACS and perfusion disorders in critically ill
      patients.

PMID- 23957752
TI  - A review of drug therapy for functional dyspepsia.
AB  - The management of functional dyspepsia (FD) is a challenge for
      gastroenterologists in clinical practice. The eradication of Helicobacter pylori
      (H. pylori) and the utility of antacids, prokinetics and antidepressants are
      recommended as treatment choices for FD by consensus. Unlike in Europe and the
      USA, H. pylori eradication in Asia can lead to a higher proportion of FD patients
      with symptom relief and a higher symptom response rate to prokinetics. Moreover,
      response rates to anti-secretory drugs such as proton pump inhibitors deviate
      considerably from those in the Western world. Digestive enzymes and probiotics
      have also been reported to be used for the treatment of FD but evidence of their
      effectiveness is not adequate. Anti-anxiety drugs and antidepressants are
      reported to have peculiar effects on FD, especially in refractory FD, in which
      tricyclic antidepressants and selective serotonin reuptake inhibitors at small
      doses are most often recommended. When these drugs are selected to treat FD,
      clinicians should also consider their roles in treating mental disorders as well
      as the direct effects of neurotransmitters on gastroenterological disorders.
      However, their effects need to be further verified by prospective double-blinded
      randomized clinical trials with a large sample size. Distinguishing among
      different symptom subtypes has limited significance in guiding the medical choice
      for FD and individualized drug treatment should be recommended in its management.

PMID- 23957754
TI  - Changes in higher-order aberrations after iris-fixated phakic intraocular lens
      implantation.
AB  - PURPOSE: To evaluate surgically induced changes in corneal, internal, and ocular
      higher-order aberrations (HOAs) after phakic intraocular lens (PIOL) implantation
      and compare them between two PIOLs with different pupillary diameters. METHODS:
      Twenty-three eyes with an Artisan PIOL (Ophtec BV, Groningen, The Netherlands)
      (Artisan group) and 30 eyes with an Artiflex PIOL (Ophtec BV) (Artiflex group)
      were retrospectively evaluated. The corneal, internal, and ocular HOAs and
      refractive data were recorded preoperatively and 6 months postoperatively. The
      root mean squares (RMSs) of the total HOAs from the third- to sixth-order Zernike
      coefficients were calculated. The RMSs of the third- and fourth-order
      coefficients represented coma-like aberrations (S3) and spherical-like
      aberrations (S4), respectively. The main outcome measures were the differences in
      the parameters among the groups with different pupillary diameters. RESULTS: The
      mean postoperative spherical equivalents decreased from -11.84 +/- 4.90 to -0.16
      +/- 0.40 diopters and -9.78 +/- 3.20 to -0.09 +/- 0.26 diopters in the Artisan
      and Artiflex groups, respectively. With the 4- and 5-mm pupillary diameters, the
      postoperative internal and ocular spherical aberrations (Z4(0)) were
      significantly lower in the Artiflex group than in the Artisan group (4 mm, P =
      .002, .024; 5 mm, P = .004, .022, respectively). With the 6-mm pupillary
      diameter, there were no significant postoperative differences in any parameter
      measured between groups; both groups had positive spherical aberration values.
      CONCLUSIONS: The postoperative ocular spherical aberrations were positive after
      Artisan and Artiflex implantation. The postoperative ocular spherical aberration
      was greater in the Artisan group, possibly due to differences in the SAs of both
      PIOLs.

PMID- 23957753
TI  - Mapping the sex determination locus in the Atlantic halibut (Hippoglossus
      hippoglossus) using RAD sequencing.
AB  - BACKGROUND: Atlantic halibut (Hippoglossus hippoglossus) is a high-value, niche
      market species for cold-water marine aquaculture. Production of monosex female
      stocks is desirable in commercial production since females grow faster and mature
      later than males. Understanding the sex determination mechanism and developing
      sex-associated markers will shorten the time for the development of monosex
      female production, thus decreasing the costs of farming. RESULTS: Halibut
      juveniles were masculinised with 17 alpha-methyldihydrotestosterone (MDHT) and
      grown to maturity. Progeny groups from four treated males were reared and sexed.
      Two of these groups (n = 26 and 70) consisted of only females, while the other
      two (n = 30 and 71) contained balanced sex ratios (50% and 48% females
      respectively). DNA from parents and offspring from the two mixed-sex families
      were used as a template for Restriction-site Associated DNA (RAD) sequencing. The
      648 million raw reads produced 90,105 unique RAD-tags. A linkage map was
      constructed based on 5703 Single Nucleotide Polymorphism (SNP) markers and 7
      microsatellites consisting of 24 linkage groups, which corresponds to the number
      of chromosome pairs in this species. A major sex determining locus was mapped to
      linkage group 13 in both families. Assays for 10 SNPs with significant
      association with phenotypic sex were tested in both population data and in 3
      additional families. Using a variety of machine-learning algorithms 97% correct
      classification could be obtained with the 3% of errors being phenotypic males
      predicted to be females. CONCLUSION: Altogether our findings support the
      hypothesis that the Atlantic halibut has an XX/XY sex determination system.
      Assays are described for sex-associated DNA markers developed from the RAD
      sequencing analysis to fast track progeny testing and implement monosex female
      halibut production for an immediate improvement in productivity. These should
      also help to speed up the inclusion of neomales derived from many families to
      maintain a larger effective population size and ensure long-term improvement
      through selective breeding.

PMID- 23957755
TI  - Femtosecond laser-assisted cataract surgery without ophthalmic viscosurgical
      devices.
AB  - PURPOSE: To describe a technique for performing femtosecond laser-assisted
      cataract surgery without the use of ophthalmic viscosurgical devices (OVDs).
      METHODS: After laser pretreatment, the anterior chamber is stabilized with
      balanced salt solution during lens and cortex aspiration. A preloaded intraocular
      lens is implanted under irrigation. RESULTS: In 23 eyes undergoing surgery
      without the use of OVDs, no complications were observed within a 1-month follow
      up period. The time for surgery and the amount of fluid that went into the eye
      were similar to those of a standard procedure. There was no remarkable increase
      in intraocular pressure or corneal thickness. All patients achieved a significant
      increase in corrected distance visual acuity after surgery. CONCLUSIONS: The
      significant reduction of phacoemulsification use after femtosecond laser
      application might render the use of OVDs obsolete in many cases.

PMID- 23957756
TI  - Construction of dispirocyclopentanebisoxindoles via self-domino Michael-aldol
      reactions of 3-phenacylideneoxindoles.
AB  - A simple protocol for the construction of novel dispirocyclopentanebisoxindoles
      is accomplished by the base promoted domino reactions between two molecules of 3
      phenacylideneoxindoles with the participation of solvents, alcohol, or other
      added nucleophiles such as amines or thiophenols. Significantly, this domino
      reaction results in the complex dispiro compounds with high yields and
      diastereoselectivity, which would allow construction of
      dispirocyclopentanebisoxindole with four and five diastereoisomeric centers using
      simple materials. 

PMID- 23957757
TI  - Transconjunctival entropion repair - the backdoor approach.
AB  - PURPOSE: To present a modified transconjunctival approach for involutional
      entropion repair. METHODS: This study is a retrospective consecutive single
      surgeon case series using a transconjunctival approach for involutional lower lid
      entropion (ILLE) repair. RESULTS: Eleven eyes were operated for involution
      entropion with 9 cases of complete resolution. Two patients required further
      Jones' retractor plication. CONCLUSION: Transconjunctival involutional lower lid
      entropion repair is a time-efficient, safe, and efficacious technique. The scar
      free technique described leads to full restoration of lower lid anatomy. In
      contrast to other reports we found a relatively low rate of recurrence on follow
      up.

PMID- 23957758
TI  - Development of biodegradable polycaprolactone film as an internal fixation
      material to enhance tendon repair: an in vitro study.
AB  - BACKGROUND: Current tendon repair techniques do not provide sufficient tensile
      strength at the repair site, and thus early active motion rehabilitation after
      tendon repair is discouraged. To enhance the post-operative tensile strength, we
      proposed and tested an internal fixation technique using a polycaprolactone (PCL)
      biofilm. PCL was chosen for its good biocompatibility, excellent mechanical
      strength, and an appropriate degradation time scale. METHODS: PCL biofilms were
      prepared by a modified melt-molding/leaching technique, and the physical and
      mechanical properties and in vitro degradation rate were assessed. The pore size
      distribution of the biofilm and the paratenon of native tendons were observed
      using scanning electron microscopy. Next, we determined whether this biofilm
      could enhance the tensile strength of repaired tendons. We performed tensile
      tests on rabbit Achilles tendons that were first lacerated and then repaired: 1)
      using modified Kessler suture combined with running peripheral suture ('control'
      group), or 2) using biofilm to wrap the tendon and then fixation with sutures
      ('biofilm' group). The influence of different repair techniques on tendon tensile
      strength was evaluated by mechanical testing. RESULTS: The novel biofilm had
      supple texture and a smooth surface. The mean thickness of the biofilm was 0.25
      mm. The mean porosity of the biofilm was 45.3%. The paratenon of the rabbit
      Achilles tendon had pores with diameters ranging from 1 to 9 MUm, which were
      similar to the 4-12 MUm diameter pores in the biofilm cross-section. The weight
      loss of the biofilms at 4 weeks was only 0.07%. The molecular weight of PCL
      biofilms did not change after immersion in phosphate buffered saline for 4 weeks.
      The failure loads of the biofilm were similar before (48 +/- 9 N) and after
      immersion (47 +/- 7 N, P > 0.1). The biofilm group had ~70% higher mean failure
      loads and 93% higher stiffness compared with the control group. CONCLUSIONS: We
      proposed and tested an internal fixation technique using a PCL biofilm to enhance
      tendon repair. Internal fixation with the biofilm followed by standard suturing
      can significantly increase the tensile strength of tendon repair sites. This
      technique has the potential to allow active motion rehabilitation during the
      early post-operative period.

PMID- 23957759
TI  - A network meta-analysis of randomized controlled trials for comparing the
      effectiveness and safety profile of treatments with marketing authorization for
      relapsing multiple sclerosis.
AB  - WHAT IS KNOWN AND OBJECTIVE: The relative effectiveness and safety profile of the
      treatments with marketing authorization for relapsing multiple sclerosis (MS) are
      not well known because randomized controlled trials with head-to-head comparisons
      between these treatments do not exist. Thus, a network of multiple-treatments
      meta-analysis was performed using four clinical outcomes: 'patients free of
      relapse', 'patients without disease progression', 'patients without MRI
      progression' and 'patients with adverse events'. METHODS: Randomized controlled
      trials (RCTs) on MS were systematically searched in PubMed and Cochrane Central
      Register of Controlled Trial. The network analysis performed pairwise comparisons
      between the marketed treatments (Betaferon 250mcg, Avonex 30mcg, Rebif 44mcg,
      Rebif 22mcg, Aubagio 7 mg, Aubagio 14 mg, Copaxone 20 mg, Tysabri 300 mg, Gilenya
      0.5 mg and Novantrone 12 mg/m(2)) using direct and indirect analyses. RESULTS AND
      DISCUSSION: The analysis included 48 articles, involving 20 455 patients with MS.
      The direct analysis showed better response for more than one outcome for Gilenya
      compared with Avonex ('patients free of relapse' and 'patients without MRI
      progression') and for Betaferon compared with Avonex ('patients without disease
      progression' and 'patients without MRI progression'). The indirect analysis
      indicated that Tysabri may have better relative effectiveness compared with the
      other treatments for two outcomes: 'patients free of relapse' and 'patients
      without MRI progression'. Regarding 'patients with adverse events', no data were
      available for all comparisons to make fair inferences. WHAT IS NEW AND
      CONCLUSION: This was an attempt, for the first time, to compare the efficacy and
      safety profile of existing approved treatments for relapsing MS. Although some
      treatments have shown better response, the results of the network analysis should
      be interpreted with caution because of the lack of RCTs with head-to-head
      comparisons between treatments.

PMID- 23957760
TI  - Intragenomic heterogeneity in the 16S rRNA genes of Flavobacterium columnare and
      standard protocol for genomovar assignment.
AB  - Genetic variability in 16S rRNA gene sequences has been demonstrated among
      isolates of Flavobacterium columnare, and a restriction fragment length
      polymorphism (RFLP) assay is available for genetic typing of this important fish
      pathogen. Interpretation of restriction patterns can be difficult due to the lack
      of a formal description of the expected number and sizes of DNA fragments
      generated for each of the described genomovars. In this study, partial 16S rRNA
      gene sequences (ca. 1250-bp fragment) from isolates representing each described
      genomovar and isolates generating unique restriction patterns were cloned and
      sequenced. The results demonstrated that some isolates contained up to three
      different 16S rRNA genes whose sequences generate different RFLP patterns due to
      intragenomic heterogeneity within HaeIII restriction sites. The occurrence of
      HaeIII restriction sites within the portion of the 16S rRNA gene used for typing
      the F. columnare isolates and intragenomic heterogeneity within these sites
      explained the restriction patterns observed following RFLP analyses. This
      research provides a standard protocol for typing isolates of F. columnare by RFLP
      and a formal description of the expected restriction patterns for the previously
      described genomovars I, II, II-B and III. Additionally, we describe a new
      genomovar, I/II. 

PMID- 23957761
TI  - Drugs targeting the bone microenvironment: new therapeutic tools in Ewing's
      sarcoma?
AB  - INTRODUCTION: Ewing's sarcoma (ES) is the second most frequent malignant primary
      bone tumour in children, adolescents and young adults. The overall survival is 60
      - 70% at 5 years but still very poor for patients with metastases, disease
      relapse or for those not responding to chemotherapy. For these high risk
      patients, new therapeutic approaches are needed beyond conventional therapies
      (chemotherapy, surgery and radiation) such as targeted therapies. AREAS COVERED:
      Transcriptomic and genomic analyses in ES have revealed alterations in genes that
      control signalling pathways involved in many other cancer types. To set up more
      specific approaches, it is reasonable to think that the particular
      microenvironment of these bone tumours is essential for their initiation and
      progression, including in ES. To support this hypothesis, preclinical studies
      using drugs targeting bone cells (bisphosphonate zoledronate, anti-receptor
      activator of NF-kappaB ligand strategies) showed promising results in animal
      models. This review will discuss the new targeted therapeutic options in ES,
      focusing more particularly on the ones modulating the bone microenvironment.
      EXPERT OPINION: Targeting the microenvironment represents a new option for
      patients with ES. The proof-of-concept has been demonstrated in preclinical
      studies using relevant animal models, especially for zoledronate, which induced a
      strong inhibition of tumour progression in an orthotopic bone model.

PMID- 23957762
TI  - Age-related differences in the distractor previewing effect with schematic faces
      of emotions.
AB  - Young and older adults searched for a unique face in a set of three schematic
      faces and identified a secondary feature of the target. The faces could be
      negative, positive, or neutral. Young adults were slower and less accurate in
      searching for a negative face among neutral faces when they had previewed a
      display of negative faces than when they had previewed neutral faces, indicating
      an emotional distractor previewing effect (DPE), but this effect was eliminated
      with inverted faces. The DPE is an index of inter-trial inhibition to keep
      attention away from previewed, non-target information. Older adults also showed
      such an emotional DPE, but it was present with both upright and inverted faces.
      These results show that, in general, both young and old participants are
      sensitive to trial history, yet the different patterns of results suggest that
      these two groups remember and use different types of perceptual information when
      searching through emotional faces.

PMID- 23957764
TI  - Work-family enrichment among dual-earner couples: can work improve our family
      life?
AB  - The extent to which resources generated at work and positive affect were
      associated with enrichment in the family domain among 107 dual-earner couples was
      investigated. Grounded in work-family enrichment theory (Greenhaus & Powell,
      2006), this study examined the indirect effect of workplace organizational
      support on family satisfaction through positive affect at work. Organizational
      support for work-family management was associated with positive affect at work
      for both women and men, and positive affect at work was related to family
      satisfaction for women. One interpersonal effect emerged: women's positive affect
      at work was associated with family satisfaction for men. Implications for theory,
      practice, research, and workplace policy are discussed.

PMID- 23957763
TI  - Gold(I)-catalyzed enantioselective carboalkoxylation of alkynes.
AB  - A highly enantioselective carboalkoxylation of alkynes catalyzed by cationic
      (DTBM-MeO-Biphep)gold(I) complexes is reported. Various optically active beta
      alkoxyindanone derivatives were obtained in good yields with high
      enantioselectivities. Furthermore, this methodology was extended to the
      enantioselective synthesis of 3-methoxycyclopentenones. The reaction is proposed
      to proceed through an enantioselective cyclization of intermediates containing
      vinylgold(I) and prochiral oxocarbenium moieties. 

PMID- 23957765
TI  - The contribution of the quality of therapists' personal lives to the development
      of the working alliance.
AB  - Research suggests that the person of the psychotherapist is important for the
      process and outcome of psychotherapy, but little is known about the relationship
      between therapists' personal experiences and the quality of their therapeutic
      work. This study investigates 2 factors (Personal Satisfactions and Personal
      Burdens) reflecting therapists' quality of life that emerged from the self
      reports of a large international sample of psychotherapists (N = 4,828) (Orlinsky
      & Ronnestad, 2004, 2005) using the Quality of Personal Life scales of the
      Development of Psychotherapists Common Core Questionnaire (Orlinsky et al.,
      1999). These factors were investigated as predictors of alliance levels and
      growth (using the Working Alliance Inventory) rated by both patients and
      therapists in a large (227 patients and 70 therapists) naturalistic outpatient
      psychotherapy study (Havik et al., 1995). The Personal Burdens scale was strongly
      and inversely related to the growth of the alliance as rated by the patients, but
      was unrelated to therapist-rated alliance. Conversely, the factor scale of
      therapists' Personal Satisfactions was clearly and positively associated with
      therapist-rated alliance growth, but was unrelated to the patients' ratings of
      the alliance. The findings suggest that the working alliance is influenced by
      therapists' quality of life, but in divergent ways when rated by patients or by
      therapists. It seems that patients are particularly sensitive to their
      therapists' private life experience of distress, which presumably is communicated
      through the therapists' in-session behaviors, whereas the therapists' judgments
      of alliance quality were positively biased by their own sense of personal well
      being.

PMID- 23957766
TI  - Reducing the stigma associated with seeking psychotherapy through self
      affirmation.
AB  - Psychotherapy may be underutilized because people experience self-stigma-the
      internalization of public stigma associated with seeking psychotherapy. The
      purpose of this study was to experimentally test whether the self-stigma
      associated with seeking psychotherapy could be reduced by a self-affirmation
      intervention wherein participants reflected on an important personal
      characteristic. Compared with a control group, we hypothesized that a self
      affirmation writing task would attenuate self-stigma, and thereby evidence
      indirect effects on intentions and willingness to seek psychotherapy.
      Participants were 84 undergraduates experiencing psychological distress. After
      completing pretest measures of self-stigma, intentions, and willingness to seek
      psychotherapy, participants were randomly assigned to either a self-affirmation
      or a control writing task, and subsequently completed posttest measures of self
      stigma, intentions, and willingness to seek psychotherapy. Consistent with
      hypotheses, participants who engaged in self-affirmation reported lower self
      stigma at posttest. Moreover, the self-affirmation writing task resulted in a
      positive indirect effect on willingness to seek psychotherapy, though results
      failed to support an indirect effect on intentions to seek psychotherapy.
      Findings suggest that self-affirmation theory may provide a useful framework for
      designing interventions that seek to address the underutilization of
      psychological services through reductions in self-stigma.

PMID- 23957767
TI  - Family constellation seminars improve psychological functioning in a general
      population sample: results of a randomized controlled trial.
AB  - The study examined the efficacy of nonrecurring family constellation seminars on
      psychological health. We conducted a monocentric, single-blind, stratified, and
      balanced randomized controlled trial (RCT). After choosing their roles for
      participating in a family constellation seminar as either active participant (AP)
      or observing participant (OP), 208 adults (M = 48 years, SD = 10; 79% women) from
      the general population were randomly allocated to the intervention group (IG; 3
      day family constellation seminar; 64 AP, 40 OP) or a wait-list control group
      (WLG; 64 AP, 40 OP). It was predicted that family constellation seminars would
      improve psychological functioning (Outcome Questionnaire OQ-45.2) at 2-week and 4
      month follow-ups. In addition, we assessed the impact of family constellation
      seminars on psychological distress and motivational incongruence. The IG showed
      significantly improved psychological functioning (d = 0.45 at 2-week follow-up, p
      = .003; d = 0.46 at 4-month follow-up, p = .003). Results were confirmed for
      psychological distress and motivational incongruence. No adverse events were
      reported. This RCT provides evidence for the efficacy of family constellation in
      a nonclinical population. The implications of the findings are discussed.

PMID- 23957768
TI  - Alliance and outcome in varying imagery procedures for PTSD: a study of within
      person processes.
AB  - The present study examined both the intraindividual relationship between alliance
      components (task, goal, and bond) and subsequent posttraumatic stress disorder
      (PTSD) symptoms over the course of therapy and the interindividual relationships
      between the initial level of the alliance components and overall PTSD outcome.
      PTSD patients (n = 65) were randomized to either standard prolonged exposure,
      which includes imaginal exposure (IE) to the traumatic memory, or modified
      prolonged exposure, where imagery rescripting (IR) of the memory replaced IE as
      the imagery component of prolonged exposure in a 10-week residential program.
      They were assessed repeatedly (weekly) on alliance and PTSD symptom measures. The
      centering method of detrending (Curran & Bauer, 2011) was used to separate the
      variance related to the intraindividual process of change during treatment
      (within-person component) from the variance related to initial individual
      differences (between-person component). The hypothesis of a negative within
      person effect of the alliance components agreement about the tasks of therapy and
      bond on subsequent PTSD symptoms was supported for the component task agreement.
      As expected, this effect was stronger in IE than in IR. Moreover, there was a
      negative relationship between interindividual differences in initial Task and
      Bond scale scores and slope of PTSD symptoms over the course of therapy. By
      contrast, within-person variations in PTSD symptoms did not predict subsequent
      alliance components. The present results suggest the importance of agreement
      about therapy tasks during the process of IE or IR within prolonged exposure for
      PTSD patients, particularly in IE.

PMID- 23957769
TI  - Academic achievement and college persistence of African American students with
      trauma exposure.
AB  - This study examined the relationship between posttraumatic stress disorder (PTSD)
      symptomatology and college persistence in African American 1st-year students from
      2 universities. Of the 569 participants, 423 (74%) reported lifetime exposure to
      traumatic events; 20.6% of these students met the criteria for PTSD. For trauma
      exposed females, after controlling for academic and nonacademic factors, higher
      levels of PTSD symptomatology in the 1st semester of college were associated with
      increased likelihood of leaving college prior to the end of the 2nd year of
      college; the relationship between the 2 variables was partially mediated by 1st
      year grade point average (GPA). PTSD symptomatology was not significantly
      associated with academic achievement or persistence for males. For trauma-exposed
      females, in addition to PTSD symptomatology, being a student at a predominantly
      White institution and entering college with low high school GPA were identified
      as risk factors for low academic achievement and college dropout; on the other
      hand, involvement in on-campus activities and higher levels of perceived academic
      integration in the 1st semester were associated with higher 1st-year GPA, which,
      in turn, was related to increased likelihood of remaining in college. Clinical
      implications and strategies to support students with trauma exposure and PTSD are
      discussed.

PMID- 23957770
TI  - The relationship between Mexican American cultural values and resilience among
      Mexican American college students: a mixed methods study.
AB  - The current study investigated the role of cultural values in the resilience of
      Mexican American college students. Utilizing mixed methodology, 124 self
      identified Mexican American college students were asked to complete an online
      survey, including a demographic questionnaire, the Resilience Scale, Mexican
      American Cultural Values Scale, and 2 open-ended questions concerning overcoming
      adversity and cultural values. As hypothesized, Mexican American traditional
      cultural values (Familismo, Respeto, Religiosidad, and Traditional Gender Roles)
      predicted resilience, with Familismo accounting for the majority of the variance.
      Consensual qualitative research (Hill, Thompson, & Nutt Williams, 1997) was used
      to identify emergent domains and themes within the open-ended question responses.
      Traditional Mexican American Value themes included Familismo, Ethnic Identity,
      Religiosidad, Perseverance, and Respeto. Results highlight the important role
      that certain Mexican American cultural values play in providing strength for
      overcoming adversities.

PMID- 23957771
TI  - Culture and vocational interests: the moderating role of collectivism and gender
      egalitarianism.
AB  - In some cultures, individuals are free to pursue careers that match their
      personalities. In others, familial and societal expectations regarding career
      paths may restrict the links between individual personality and interests. Gender
      role expectations also may vary across cultures and may be associated with gender
      differences in interests. Past meta-analytic research has shown some career
      interests are related to personality traits (Barrick, Mount, & Gupta, 2003;
      Larson, Rottinghaus, & Borgen, 2002), but the cross-cultural variation of these
      relationships has not been sufficiently explored. Interest and personality data
      were obtained from an archival data set of 391,485 individuals from 20 countries.
      Results indicated that in cultures with high in-group collectivism, connections
      between personality traits and occupational interests may be less pronounced.
      Cultural gender egalitarianism moderated the level of gender differences in
      interests, unexpectedly demonstrating that gender differences may be wider in
      egalitarian cultures. Implications for career guidance in multicultural settings
      are discussed.

PMID- 23957772
TI  - Theoretical studies on the photoelectron and absorption spectra of MnO4(-) and
      TcO4(-).
AB  - The tetraoxo pertechnetate anion (TcO4(-)) is of great interest for nuclear waste
      management and radiopharmceuticals. To elucidate its electronic structure and to
      compare with that of its lighter congener MnO4(-), the photoelectron and
      electronic absorption spectra of MnO4(-) and TcO4(-) are investigated with
      density functional theory (DFT) and ab initio wave function theory (WFT). The
      vertical electron detachment energies (VDEs) of MnO4(-) obtained with the CR-EOM
      CCSD(T) method are in good agreement with the lowest two experimental VDEs; the
      differences are less than 0.1 eV, representing a significant improvement over the
      IP-EOM-CCSD(T) result in the literature. Combining our CCSD(T) and CR-EOM-CCSD(T)
      results, the first five VDEs of TcO4(-) are estimated between 5 and 10 eV with an
      estimated accuracy of about +/-0.2 eV. The vertical excitation energies are
      determined by using TD-DFT, CR-EOM-CCSD(T), and RAS-PT2 methods. The excitation
      energies and the assignments of the spectra are analyzed and partly improved.
      They are compared with reported SAC-CI results and available experimental data.
      Both dynamic and nondynamic electron correlations are important in the ground and
      excited states of MnO4(-) and TcO4(-). Nondynamical correlations are particularly
      relevant in TcO4(-) for reliable prediction of excitation energies. In TcO4(-)
      one Rydberg state interlaces but does not mix with the valence excited states,
      and it disappears in the condensed phase. 

PMID- 23957773
TI  - Solution structure of energy stored system I: aqua-B(OH)4(-): a DFT, Car
      Parrinello molecular dynamics, and Raman study.
AB  - A systematic study on the structure, stability, and Raman spectra of the
      metaborate anion hydrated clusters, B(OH)4(-)(H2O)n, (n = 1-15) was carried out
      by DFT in both gaseous and aqueous phase at the B3LYP/aug-cc-pVDZ level; all of
      these stable configurations were described, and the most stable hydrated clusters
      were chosen. The hydrogen bonds in those hydrated clusters were described in
      three different items: symmetrical double hydrogen bonding (DHB), single hydrogen
      bonding (SHB), and interwater hydrogen bonding (WHB). The distance of SHB is
      shorter than that of DHB, and multiple SHBs are more stable than a single DHB. In
      small size clusters (n <= 5), a structure with more DHBs is more stable than
      other arrangements. With continued increase in size, more SHBs were found in the
      first hydration sphere: when n >= 9, only SHBs can be found, and when n >= 12, a
      full hydration structure is formed with 12 SHBs and a hydration number of 10-12.
      The Car-Parrinello molecular dynamics simulation shows that only the first
      hydration sphere can be found, and the hydration number of B(OH)4(-) is 9.2 and
      the hydration distance is 3.68. The total symmetrical stretching vibration of
      B(OH)4(-) in hydrated B(OH)4(-)(H2O)n is blue shifted with increasing cluster
      size. After consideration of hydration, the calculated characteristic frequencies
      are in accord with the experiment characteristic frequency of B(OH)4(-). 

PMID- 23957774
TI  - Superhydrophobic lignocellulosic wood fiber/mineral networks.
AB  - Lignocellulosic wood fibers and mineral fillers (calcium carbonate, talc, or
      clay) were used to prepare paper samples (handsheets), which were then subjected
      to a fluorocarbon plasma treatment. The plasma treatment was performed in two
      steps: first using oxygen plasma to create nanoscale roughness on the surface of
      the handsheet, and second fluorocarbon deposition plasma to add a layer of low
      surface energy material. The wetting behavior of the resulting fiber/mineral
      network (handsheet) was determined. It was found the samples that were subjected
      to oxygen plasma etching prior to fluorocarbon deposition exhibit
      superhydrophobicity with low contact angle hysteresis. On the other hand, those
      that were only treated by fluorocarbon plasma resulted in "sticky" hydrophobicity
      behavior. Moreover, as the mineral content in the handsheet increases, the
      hydrophobicity after plasma treatment decreases. Finally, it was found that
      although the plasma-treated handsheets show excellent water repellency they are
      not good water vapor barriers. 

PMID- 23957775
TI  - Intraoperative indocyanine green video-angiography as an aid to the microsurgical
      treatment of spinal vascular malformations.
AB  - AIMS AND OBJECTIVES. Intra-operative Indocyanine Green (ICG) video-angiography
      (ICG-VA) has become an established aid to cerebrovascular surgery. We describe
      our experience using this technique to define angio-architecture intraoperatively
      in a range of spinal vascular malformations. METHODS. A retrospective review of
      notes and imaging was carried out from a prospectively maintained database. Our
      series comprises 27 patients who underwent surgical treatment between September
      2007 and August 2012. We carried out a retrospective review of data from a
      prospectively maintained database. RESULTS. For slow-flow Type 1 fistulae the ICG
      videoangiogram demonstrated conclusively that the arteriovenous shunt was
      obliterated. This is a consideration on the rare occasions where a second fistula
      is present, an example of which is included in this series. ICG-VA also helps to
      demonstrate normal vascular anatomy and distinguish these vessels from pathology.
      For Type II lesions it allowed orientation to the vascular anatomy as
      demonstrated by the pre-operative angiogram. In one of two cases in this series
      it ensured to the complete extirpation of a large arteriovenous malformation
      (AVM). However a second Type II case demonstrated its limitations, as a diffuse
      intramedullary component could not be identified. Two cases were explored where
      digital subtraction spinal angiography was not possible and incomplete
      understanding of the angio-architectures of the lesions were available from Time
      Resolved dynamic magnetic resonance angiography and/or multi-detector CT
      angiography. ICG-VA provided invaluable information on alterations in arterio
      venous flow that allowed diagnosis and obliteration of the arteriovenous shunts
      in each case. DISCUSSION. ICG video-angiography is a time-efficient and safe
      alternative to intra-operative spinal angiography. It provided useful information
      on haemodynamic changes intraoperatively and completeness of treatment. We
      discuss its limitations and role in the management of these lesions.

PMID- 23957776
TI  - Enlarging head size as the only presentation of Salmonella Typhimurium brain
      abscess in an infant: a short report.
AB  - The authors describe a 5-month-old male harbouring a giant Salmonella Typhimurium
      cerebral abscess who presented with progressively enlarging head size, without
      any features of septicemia. The report details the radiological findings,
      differential diagnoses and management problems regarding the index case.

PMID- 23957777
TI  - Isolated cerebral metastasis of a triceps muscle leiomyosarcoma: a case report.
AB  - Leiomyosarcomas are rare malignant neoplasms. Intracranial metastases of this
      tumour are even less frequently observed and have mostly been described from
      uterine leiomyosarcomas. In this article, we describe the case of a single right
      frontal subcortical cerebral metastasis in a patient with a right triceps muscle
      leiomyosarcoma. A right-sided frontal craniotomy with macroscopically complete
      tumour removal was performed, followed by combined radio-chemotherapy. The
      patient died 10 months after the initial diagnosis of the intracranial metastasis
      due to systemic tumour progression, without any evidence of intracranial
      recurrence.

PMID- 23957778
TI  - Split mesencephalon: diplomyelia of the basicranium.
AB  - We report a novel case of congenitally split mesencephalon, in a 3-year old with
      hydrocephalus. We speculate that the ontogenetic mechanism is shared with split
      cord malformations (SCM). Our case adds to the two other cases of basicranial SCM
      which involved more caudal brainstem.

PMID- 23957779
TI  - Is the rate of re-operation after primary lumbar microdiscectomy affected by
      surgeon grade or intra-operative lavage of the disc space?
AB  - STUDY DESIGN. Retrospective audit of consecutive patients. OBJECTIve. To
      investigate the re-operation rate following elective primary lumbar
      microdiscectomy and to determine whether principal surgeon grade and/or disc
      space lavage is a factor in recurrence. SUMMARY OF BACKGROUND DATA. Recurrent
      herniation of disc material following lumbar microdiscecomy surgery is one of the
      commonest complications of the procedure. Any reduction in the number of revision
      microdiscectomies performed per year would have a significant impact on patients'
      lives and on the health service economy. We undertook this study to ascertain
      whether principal surgeon grade and/or disc space lavage has an impact in
      reducing the re-operation rate. METHODS. We undertook a retrospective audit of
      patients who underwent elective primary lumbar microdiscectomy, over a 3-year
      period (n = 971). RESULTS. The overall re-operation rate for primary elective
      microdiscectomy was 3.8%, consistent with the published literature. The relative
      risk of re-operation in patients primarily operated by registrar surgeons was 1.2
      fold the risk in patients operated by consultants (95% CI: 0.62, 2.35) although
      not statistically significant (p = 0.568). The risk of re-operation in the 'non
      lavage' group was 2.15 times the risk in the 'lavage' group (95% CI: 0.63, 7.34),
      but it did not reach significance (p = 0.222). CONCLUSIONS. Principal surgeon
      grade and intervertebral disc lavage have not been found conclusively to be
      factors in the rate of recurrence. This information is useful to reassure
      patients that their outcome from such surgery is not dependent on the grade of
      surgeon performing the operation. There is a possible trend towards
      intervertebral disc lavage reducing the rate of recurrence.

PMID- 23957780
TI  - Stupp-treated glioblastoma accompanied by EBV-positive primary CNS lymphoma.
AB  - We describe a patient who within 2 months of undergoing radio-chemotherapy for
      glioblastoma developed an Epstein-Barr virus-positive primary diffuse large B
      cell CNS lymphoma. To our knowledge, this is the first such case reported in the
      literature showing that new tumefactions following aggressive treatment for
      glioblastomata might represent secondary malignancies.

PMID- 23957781
TI  - Morning plasma cortisol is low among obese women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is the most common cause for androgen excess in
      women. It is associated with wide variety of metabolic disorders. The present
      study assessed morning plasma cortisol in women with PCOS. One hundred and ninety
      seven cases and 55 controls were enrolled for this study. The mean age of
      patients and controls were 23 +/- 5.6 years and 25 +/- 4.3 years. One hundred
      twelve (56%) women with PCOS had BMI >25. Serum cortisol levels were
      significantly higher in lean PCOS women compared to controls (13.4 +/- 5.1 versus
      11.3 +/- 4.5, p < 0.01) and over-weight PCOS women group (13.4 +/- 5.1 versus 9.3
      +/- 3.2, p < 0.01). There was a trend for less acne and hirsutism with increase
      in BMI. Morning plasma cortisol was lower among obese women with PCOS. Morning
      plasma cortisol correlated negatively with BMI in PCOS women with normal glucose
      tolerance.

PMID- 23957782
TI  - Alterations in thyroid function among the different polycystic ovary syndrome
      phenotypes.
AB  - The study evaluates the prevalence of subclinical thyroid dysfunction in
      infertile PCOS patients, according to the different PCOS phenotypes and to
      examine whether insulin sensitizers in insulin resistant (IR) PCOS patients may
      improve thyroid function. The study population consisted of all PCOS patients,
      attending the infertility and IVF unit of Department of Pediatrics, Obstetrics
      and Reproductive Medicine of University of Siena, Italy, and compared them to
      regularly cycling, healthy, infertile controls. Upon admission, blood was drawn
      from all patients during the early follicular phase, for complete hormonal and
      metabolic profiles. In IR-PCOS patients treated with insulin sensitizers, blood
      was drawn again after 6 months. PCOS patients had a significantly higher
      prevalence of subclinical thyroid dysfunction compared to infertile controls.
      While no significant association was detected between TSH value and the presence
      of hyperandrogenism, overweight and obese PCOS patients, as well as IR PCOS
      patients showed significantly higher prevalence of subclinical thyroid
      dysfunction. Moreover, among IR PCOS patients, 6 months treatment with insulin
      sensitizers significantly reduces TSH levels. Infertile PCOS patients have a high
      prevalence of subclinical thyroid dysfunction, which may be successfully treated
      in IR PCOS patients by insulin sensitizers.

PMID- 23957784
TI  - Experimental model for bone regeneration in oral and cranio-maxillo-facial
      surgery.
AB  - Bone and tooth loss, as a result of trauma, anatomical or congenital reasons,
      cancer, and periodontal disease, is a common therapeutic problem in the fields of
      cranio-maxillo-facial surgery and periodontics. The proposed techniques for the
      treatment of various bone defects encountered include bone grafts, bone
      substitutes, guided tissue regeneration, and distraction osteogenesis as well as
      their combinations. In addition, dental implants have been successfully utilized
      for the restoration of full or partial edentulism. The introduction and
      development of new therapeutic approaches and devices demand the use of
      appropriate animal models that present bone anatomy and healing comparable to
      human. Among other animal models, the pig is extensively documented in several
      biomedical areas and has been largely used in maxillo-facial surgery and implants
      dentistry-related research. Anatomical and physiological similarities with human
      in size, physiology, and bone biology contribute to a successful involvement of
      this animal to understand and treat various osseous lesions. However,
      improvements and standardization are requested with respect to consistency and
      discrimination abilities. The aim of this review is to provide a critical
      appraisal of the literature related to swine models for the evaluation of cranio
      maxillo-facial osseous defect healing, regeneration, and bone-implant interface.
      This review should assist researchers in the field to select the most appropriate
      model for each dedicated purpose and also contribute to stimulate an innovative
      thinking on the use of porcine models.

PMID- 23957785
TI  - Genomics of medical importance.

PMID- 23957783
TI  - Crucial roles of Nox2-derived oxidative stress in deteriorating the function of
      insulin receptors and endothelium in dietary obesity of middle-aged mice.
AB  - BACKGROUND AND PURPOSE: Systemic oxidative stress associated with dietary calorie
      overload plays an important role in the deterioration of vascular function in
      middle-aged patients suffering from obesity and insulin resistance. However,
      effective therapy is still lacking. EXPERIMENTAL APPROACH: In this study, we used
      a mouse model of middle-aged obesity to investigate the therapeutic potential of
      pharmaceutical inhibition (apocynin, 5 mM supplied in the drinking water) or
      knockout of Nox2, an enzyme generating reactive oxygen species (ROS), in high-fat
      diet (HFD)-induced obesity, oxidative stress, insulin resistance and endothelial
      dysfunction. Littermates of C57BL/6J wild-type (WT) and Nox2 knockout (KO) mice
      (7 months old) were fed with a HFD (45% kcal fat) or normal chow diet (NCD, 12%
      kcal fat) for 16 weeks and used at 11 months of age. KEY RESULTS: Compared to NCD
      WT mice, HFD WT mice developed obesity, insulin resistance, dyslipidaemia and
      hypertension. Aortic vessels from these mice showed significantly increased Nox2
      expression and ROS production, accompanied by significantly increased ERK1/2
      activation, reduced insulin receptor expression, decreased Akt and eNOS
      phosphorylation and impaired endothelium-dependent vessel relaxation to
      acetylcholine. All these HFD-induced abnormalities (except the hyperinsulinaemia)
      were absent in apocynin-treated WT or Nox2 KO mice given the same HFD.
      CONCLUSIONS AND IMPLICATIONS: In conclusion, Nox2-derived ROS played a key role
      in damaging insulin receptor and endothelial function in dietary obesity after
      middle-age. Targeting Nox2 could represent a valuable therapeutic strategy in the
      metabolic syndrome.

PMID- 23957786
TI  - Prospective survey of acute osteoarticular infections in a French paediatric
      orthopedic surgery unit.
AB  - The epidemiology of acute paediatric osteoarticular infections (OAI) has recently
      evolved, mainly due to the improvement of microbiological diagnosis. We conducted
      a prospective study to analyse the recent epidemiology and the clinical evolution
      of paediatric OAI in order to validate the adequacy of our probabilistic first
      line antibiotic treatment (intraveinous cefamandole + gentamicin). All children
      suspected of community acquired OAI were included and followed-up for 3 years.
      The etiologic diagnosis was based on blood cultures, joint aspirations and bone
      punctures. All osteoarticular (OA) samples were systematically inoculated into
      blood culture bottles. Real-time universal 16S rRNA and PCR targeted on
      Staphylococcus aureus, Kingella kingae, Streptococcus pneumoniae and
      Streptococcus pyogenes were performed twice a week. From 17 March 2007 to 26
      February 2009, 98 septic arthritis, 70 osteomyelitis, 23 osteoarthritis and six
      spondylodiscitis were analysed. A portal of entry was suspected in 44% of cases,
      including 55% of otorhinolaryngological infections. C reactive protein was the
      most sensitive inflammatory marker. PCR increased by 54% the performance of
      bacteriological diagnosis. Among the patients completely investigated (blood
      culture and OAI samples), there were 63% documented OAI. The main pathogens found
      were K. kingae (52%), S. aureus (28%), S. pyogenes (7%), S. pneumoniae (3%) and
      Streptococcus agalactiae (2%). All isolated bacteria were sensitive to the
      probabilist treatment and outcome was favorable. PCR has significantly improved
      the performance and the delay of IOA diagnosis in children, for which K. kingae
      turned out to be the first causative agent. The probabilistic treatment was
      active against the main bacteria responsible for paediatric OAI.

PMID- 23957788
TI  - Effects of chronic NMDA-NR2b inhibition in the median eminence of the
      reproductive senescent female rat.
AB  - Gonadotrophin-releasing hormone (GnRH) neurones of the hypothalamic-pituitary
      gonadal (HPG) axis drive reproductive function and undergo age-related decreases
      in activation during the transition to reproductive senescence. Decreased GnRH
      secretion from the median eminence (ME) partially arises from attenuated
      glutamatergic signalling via the NMDA receptor (NMDAR) and may be a result of
      changing NMDAR stoichiometry to favour NR2b over NR2a subunit expression with
      ageing. We have previously shown that the systemic inhibition of NR2b-containing
      receptors with ifenprodil, an NR2b-specific antagonist, stimulates parameters of
      luteinising hormone (used as a proxy for GnRH) release in both young and middle
      aged females. In the present study, we chronically administered ifenprodil, an
      NR2b-specific antagonist, at the site of GnRH terminals in the ME or at GnRH
      perikarya in the preoptic area, in reproductively senescent middle-aged female
      rats, aiming to determine whether NR2b antagonism could restore aspects of
      reproductive functionality. Effects on oestrous cyclicity, serum hormones, and
      protein expression of GnRH, NR2b and phosphorylated NR2b (Tyr-1472) in the ME
      were measured. Chronic ifenprodil treatment in the ME (but not the preoptic area)
      altered oestrous cyclicity by increasing the percentage of days spent in pro
      oestrus. This was accompanied by increased GnRH fluorescence intensity in the
      external ME zone and a greater proportion of GnRH terminals that co-labelled with
      pNR2b with treatment. We also observed changes in the relationships between
      protein immunofluorescence, serum hormone levels and other aspects of
      reproductive physiology in acyclic females, as revealed by bionetwork analysis.
      Together, these data support the hypothesis that NMDAR-NR2b expression and
      phosphorylation state play a role in reproductive senescence and highlight the ME
      as a major player in reproductive ageing. 

PMID- 23957790
TI  - Stereospecific asymmetric N-heterocyclic carbene (NHC)-catalyzed redox synthesis
      of trifluoromethyl dihydropyranones and mechanistic insights.
AB  - N-heterocyclic carbene (NHC)-catalyzed redox asymmetric hetero-Diels-Alder
      reactions of alpha-aroyloxyaldehydes with beta-trifluoromethyl enones generates
      synthetically useful dihydropyranones containing a stereogenic trifluoromethyl
      substituent in good yields (up to 81%) and excellent diastereoselectivity and
      enantioselectivity (up to >95:5 dr and >99% ee). The process is stereospecific,
      with use of either (E)- or (Z)-beta-trifluoromethyl enones forming syn- or anti
      dihydropyranone products, respectively. Mechanistic studies through in situ
      kinetic analysis of the reaction reveal key differences in reactivity between
      chiral NHC precursor 1 and an achiral NHC precursor.

PMID- 23957789
TI  - Molecular signatures of mammalian hibernation: comparisons with alternative
      phenotypes.
AB  - BACKGROUND: Mammalian hibernators display phenotypes similar to physiological
      responses to calorie restriction and fasting, sleep, cold exposure, and ischemia
      reperfusion in non-hibernating species. Whether biochemical changes evident
      during hibernation have parallels in non-hibernating systems on molecular and
      genetic levels is unclear. RESULTS: We identified the molecular signatures of
      torpor and arousal episodes during hibernation using a custom-designed microarray
      for the Arctic ground squirrel (Urocitellus parryii) and compared them with
      molecular signatures of selected mouse phenotypes. Our results indicate that
      differential gene expression related to metabolism during hibernation is
      associated with that during calorie restriction and that the nuclear receptor
      protein PPARalpha is potentially crucial for metabolic remodeling in torpor.
      Sleep-wake cycle-related and temperature response genes follow the same
      expression changes as during the torpor-arousal cycle. Increased fatty acid
      metabolism occurs during hibernation but not during ischemia-reperfusion injury
      in mice and, thus, might contribute to protection against ischemia-reperfusion
      during hibernation. CONCLUSIONS: In this study, we systematically compared
      hibernation with alternative phenotypes to reveal novel mechanisms that might be
      used therapeutically in human pathological conditions.

PMID- 23957791
TI  - Become an author and share your knowledge.

PMID- 23957792
TI  - The psychological impact of medical Trauma: one woman's childbirth story.

PMID- 23957794
TI  - Postpartum and neonatal nursing care during the 2009 H1N1 influenza pandemic.
AB  - We describe select influenza infection control policies and practices related to
      postpartum and newborn care during the 2009 H1N1 pandemic. In an online survey of
      obstetric and neonatal nurses, significantly more nurses indicated a written
      hospital policy supporting each of the practices during versus before the
      pandemic. The two practices least often implemented were temporary separation of
      healthy newborns from ill mothers (37.7 percent) and testing newborns for
      influenza virus infection if signs of influenza were observed (31.4 percent).
      Presence of written hospital policies increased implementation of practices.
      Findings may be useful to guide planning for future pandemics or other public
      health emergencies. 

PMID- 23957795
TI  - A review of treatment and management modalities for premenstrual dysphoric
      disorder.
AB  - Premenstrual dysphoric disorder (PMDD) affects 5 to 8 percent of women and can
      significantly decrease their quality of life. Symptoms generally present during
      the late luteal phase of the menstrual cycle and can affect women emotionally,
      behaviorally, cognitively and physiologically. This article reviews the clinical
      literature on PMDD and the evidence behind various methods of symptom management.
      Evidence suggests that a holistic approach, including lifestyle modifications,
      pharmacotherapy and cognitive behavioral therapy, is most beneficial for symptom
      reduction and improvement in daily functioning and quality of life. 

PMID- 23957796
TI  - A nurse-led initiative to improve obstetricians' screening for postpartum
      depression.
AB  - Although up to 20 percent of women experience postpartum depression, screening is
      not standard practice. In a metropolitan area where only 1 of 30 obstetricians
      and two primary care clinics reported routine screening for postpartum
      depression, a nurse-led initiative to implement routine screening using the
      Edinburgh Postnatal Depression Scale was carried out. Twenty-two obstetricians
      (76 percent) agreed to consistently implement screening for 3 months. Of the 21
      participating obstetricians, 71.4 percent indicated that postpartum depression
      screening would become their standard care. This article describes implementation
      strategies and lessons learned. 

PMID- 23957797
TI  - Could your patient have an eating disorder?
AB  - Eating disorders, including anorexia nervosa, bulimia nervosa and binge eating
      disorder, affect approximately 14 million people in the U.S., three-fourths of
      whom are female. Contrary to popular belief, eating disorders affect people of
      all ages. Women's health nurses can play a vital role in identifying adolescents
      and women who may be suffering from an eating disorder and referring them for
      specialized treatment. 

PMID- 23957798
TI  - Preventing and recognizing venous thromboembolism after obstetric and gynecologic
      surgery.
AB  - Venous thromboembolism (VTE) is a hypercoagulable disorder that is associated
      with two potential significant complications-deep venous thrombosis (DVT) and
      pulmonary embolus (PE). During pregnancy and the postpartum period, the risk for
      VTE is increased. Prevention is optimal, but early detection and treatment of VTE
      in women after obstetric and gynecologic surgery is imperative, as DVT is often
      asymptomatic and, in many patients, clinical presentation only occurs after a
      fatal PE occurs. 

PMID- 23957799
TI  - Screening for breast and cervical cancer: understanding the different
      recommendations.
AB  - Evidence-based screening guidelines issued by national organizations sometimes
      contradict each other, leading to confusion among health care providers and the
      women they care for. This article summarizes the most recent guidelines for
      breast and cervical cancer screening and notes where they concur and where they
      diverge. 

PMID- 23957800
TI  - Two cases of apparent suffocation of newborns during side-lying breastfeeding.
AB  - The side-lying position is one of several options offered to women in the
      postpartum period to assist with early establishment of breastfeeding. Many new
      mothers are exhausted and experiencing significant pain following birth. While
      the side-lying position for breastfeeding can allow women to get needed rest, it
      can increase their risk of falling asleep while in this position and potentially
      smothering their babies. We report two cases of apparent suffocation in newborns
      on the maternity ward when women unintentionally fell asleep while breastfeeding
      in the side-lying position. Interventions that may help to prevent such events
      are suggested. 

PMID- 23957801
TI  - Cultivating future nurse leaders with student nurses associations.
AB  - Student nurses associations (SNAs) assist in developing tomorrow's nurse leaders.
      In this article, executive board members of an SNA in a traditional baccalaureate
      nursing program at a public regional university recounted common themes in their
      participation in an SNA. These broad themes included leadership, mentorship and
      communication, all which foster professional development through the acquisition
      of specific knowledge, skills and experiences. 

PMID- 23957804
TI  - With calm and steady hands.

PMID- 23957805
TI  - Deltoid muscle shape analysis with magnetic resonance imaging in patients with
      chronic rotator cuff tears.
AB  - BACKGROUND: It seems appropriate to assume, that for a full and strong global
      shoulder function a normally innervated and active deltoid muscle is
      indispensable. We set out to analyse the size and shape of the deltoid muscle on
      MR-arthrographies, and analyse its influence on shoulder function and its
      adaption (i.e. atrophy) for reduced shoulder function. METHODS: The fatty
      infiltration (Goutallier stages), atrophy (tangent sign) and selective
      myotendinous retraction of the rotator cuff, as well as the thickness and the
      area of seven anatomically defined segments of the deltoid muscle were measured
      on MR-arthrographies and correlated with shoulder function (i.e. active
      abduction). Included were 116 patients, suffering of a rotator cuff tear with
      shoulder mobility ranging from pseudoparalysis to free mobility. Kolmogorov
      Smirnov test was used to determine the distribution of the data before either
      Spearman or Pearson correlation and a multiple regression was applied to reveal
      the correlations. RESULTS: Our developed method for measuring deltoid area and
      thickness showed to be reproducible with excellent interobserver correlations (r
      = 0.814-0.982).The analysis of influencing factors on active abduction revealed a
      weak influence of the amount of SSP tendon (r = -0.25; p < 0.01) and muscle
      retraction (r = -0.27; p < 0.01) as well as the stage of fatty muscle
      infiltration (GFDI: r = -0.36; p < 0.01). Unexpectedly however, we were unable to
      detect a relation of the deltoid muscle shape with the degree of active
      glenohumeral abduction. Furthermore, long-standing rotator cuff tears did not
      appear to influence the deltoid shape, i.e. did not lead to muscle atrophy.
      CONCLUSIONS: Our data support that in chronic rotator cuff tears, there seems to
      be no disadvantage to exhausting conservative treatment and to delay implantation
      of reverse total shoulder arthroplasty, as the shape of deltoid muscle seems only
      to be influenced by natural aging, but to be independent of reduced shoulder
      motion.

PMID- 23957807
TI  - What can we learn from the evaluation of the Dutch National Risk Assessment?

PMID- 23957808
TI  - What can national risk assessors learn from decision theorists and psychologists?

PMID- 23957809
TI  - The Fish Invasiveness Screening Kit (FISK) for non-native freshwater fishes--a
      summary of current applications.

PMID- 23957810
TI  - Clinicopathology of recurrent hepatocellular carcinomas after radiofrequency
      ablation treated with salvage surgery.
AB  - AIM: Radiofrequency ablation (RFA) is an effective standard local therapy for
      small hepatocellular carcinoma (HCC). However, local recurrence and/or tumor
      seeding after RFA remain major problems. For better understanding of underlying
      factors, we clarified clinicopathological features of recurrent HCC treated with
      RFA. METHODS: This retrospective study included 21 patients who underwent
      surgical resection for HCC disease recurrence after RFA. Clinicopathological
      findings, including patterns of recurrence, immunohistochemical expression of
      proliferation markers (Ki-67 and p27(Kip1) ) and survival outcome were assessed.
      RESULTS: The median time interval after RFA until the diagnosis of intrahepatic
      and/or extrahepatic tumor progression was 12 months (range, 3-84). Radical
      surgical resection was attempted for intrahepatic local recurrence in 16 patients
      (18 lesions), for peritoneal dissemination in four, for lymph node metastases in
      three and for adrenal metastasis in two. In 14 of the 21 (67%) patients, the
      recurrent HCC were histologically diagnosed as of poorly differentiated type.
      Their average Ki-67 and p27(Kip1) labeling indices were significantly higher (P =
      0.020) and lower (P < 0.001), respectively, compared with values for the 108 HCC
      surgically resected at the initial treatment. Portal involvement was
      significantly higher (P = 0.01) in recurrent tumors after RFA (72%) than in HCC
      surgically resected at the initial treatment (43%). The mortality rate of salvage
      surgery was 0%, with cumulative survival rates at 1 and 3 years of 58.9% and
      35.7%, respectively. CONCLUSION: The recurrent tumors after RFA have
      characteristics of poor differentiation degree and abnormalities in cell-cycle
      regulators and are associated with aggressive vascular invasiveness.

PMID- 23957811
TI  - Cross-neutralization studies with salmonid alphavirus subtype 1-6 strains:
      results with sera from experimental studies and natural infections.
AB  - The serological reactivity between strains of each of the six currently
      genetically defined subtypes of salmonid alphavirus (SAV) was examined by
      comparison of homologous and heterologous virus neutralization titres on sera
      from experimentally infected fish. With the exception of the level of SAV subtype
      6 neutralization by heterologous sera, good cross-neutralization was detected
      between all subtypes, albeit with variation in geometric mean titres when each
      subtype-specific serum set was tested against the panel of virus subtypes. A
      similar pattern was evident with field sera, except that heterologous
      neutralization of the SAV6 strain was more evident. In only 23% of available
      pairwise comparisons was the homologous titre recorded with an experimentally
      derived serum fourfold or greater than the heterologous titre, and in only two
      instances was this difference demonstrated in both directions. No virus strains
      consistently met the old serology-based criteria (Sub-committee on Inter
      relationships Among Catalogued Alphaviruses) to be considered separate subtypes
      within an alphavirus species. Only when testing with an SAV subtype-2-specific
      monoclonal antibody was a major difference between homologous and heterologous
      neutralization capacity evident. These results provide new direct or indirect
      information in terms of SAV classification, vaccine efficacy and the selection
      and validation of reagents for serological and immunological diagnostic purposes.

PMID- 23957812
TI  - LHRH-targeted nanogels as a delivery system for cisplatin to ovarian cancer.
AB  - Targeted drug delivery using multifunctional polymeric nanocarriers is a modern
      approach for cancer therapy. Our purpose was to prepare targeted nanogels for
      selective delivery of chemotherapeutic agent cisplatin to luteinizing hormone
      releasing hormone (LHRH) receptor overexpressing tumor in vivo. Building blocks
      of such delivery systems consisted of innovative soft block copolymer nanogels
      with ionic cores serving as a reservoir for cisplatin (loading 35%) and a
      synthetic analogue of LHRH conjugated to the nanogels via poly(ethylene glycol)
      spacer. Covalent attachment of (D-Lys6)-LHRH to nanogels was shown to be possible
      without loss in either the ligand binding affinity or the nanogel drug
      incorporation ability. LHRH-nanogel accumulation was specific to the LHRH
      receptor positive A2780 ovarian cancer cells and not toward LHRH-receptor
      negative SKOV-3 cells. The LHRH-nanogel cisplatin formulation was more effective
      and less toxic than equimolar doses of free cisplatin or untargeted nanogels in
      the treatment of receptor-positive ovarian cancer xenografts in mice.
      Collectively, the study indicates that LHRH mediated nanogel-cisplatin delivery
      is a promising formulation strategy for therapy of tumors that express the LHRH
      receptor.

PMID- 23957813
TI  - The long-term follow-up results of external dacryocystorhinostomy skin incision
      scar with "W incision".
AB  - OBJECTIVE: To determine the effect of "W incision" instead of classical vertical
      incision at external DCR on scar formation. MATERIALS AND METHODS: Patients with
      acquired nasolacrimal duct obstruction (NLDO) who were treated with external DCR
      with classical vertical incision, and patients who were treated with external DCR
      with "W incision" were included in the study. The first 39 eyes were operated
      with a vertical incision, and the remaining 37 eyes were operated with a "W
      incision". All the skin incision scars of the patients were assessed and scored
      by at least the 6th month. The assessment was made by both the patients
      themselves, and by an ophthalmologist other than the surgeon himself, each scored
      the incision scar separately (single-masked study). Scores for both groups were
      compared, and statistical analyses were performed. RESULTS: Self-assessment
      scores for the incision scar were Grade 2.28 +/- 0.94 in the Vertical incision
      group, and Grade 1.68 +/- 0.57 in the "W incision" group (p < 0.01). The "W
      incision" scar formation was significantly less noticable than the Vertical
      incision scar formation. Similarly, the assessment scores of the ophthalmologist
      other than the surgeon himself were significantly lower for the "W incision"
      group than for the Vertical incision group. The mean scar assessment scores were
      Grade 2.13 +/- 0.95 in the Vertical incision group, and Grade 1.57 +/- 0.68 in
      the "W incision" group (p < 0.01). CONCLUSION: Skin scar tissue was found to be
      significantly reduced with a "W incision" in external DCR operations.

PMID- 23957814
TI  - Establishment of the metabolite profile for an Antrodia cinnamomea health food
      product and investigation of its chemoprevention activity.
AB  - Antrodia cinnamomea is an edible fungus endemic to Taiwan that has been
      attributed with health promotion benefits. An A. cinnamomea mycelium health food
      product, which was produced by solid-state culture, was selected as the target
      for investigation in this study. Fourteen representative metabolites of A.
      cinnamomea mycelium (EMAC) were selected as index compounds to establish the
      metabolite profile for evaluation of EMAC product quality. It was also
      demonstrated that EMAC administration significantly reduced liver inflammation
      and serum oxidative stress in vivo. 4-Acetylantroquinonol B obtained by a
      bioactivity-guided fractionation from EMAC was able to not only inhibit LPS
      induced nitric oxide formation in macrophages but also protect against ethanol
      induced oxidative stress in liver cells. The results suggest this A. cinnamomea
      product might be a potent antioxidative and anti-inflammatory supplement for
      chemoprevention. 

PMID- 23957815
TI  - Cathepsin K inhibitors: a novel target but promising approach in the treatment of
      osteoporosis.
AB  - Osteoporosis is a pathologic process characterized by low bone mass with skeletal
      fragility and an increased risk of fracture. It occurs due to an imbalance
      between bone resorption and formation. Although current antiresorptive therapy
      halts bone loss, it does not cure the condition as it also inhibits bone
      formation. Recent preclinical and clinical trials suggest that the inhibition of
      resorption by cathepsin K inhibitors increases bone formation. Cathepsin K is a
      papainlike cysteine protease with high potent collagenase activity and
      predominantly expressed in osteoclasts. While allowing demineralization,
      cathepsin K inhibitors suppress the degradation of type I collagen (the major
      organic matrix of bone) and thus enhancing bone formation. Many of these
      inhibitors have passed preclinical studies and are presently in clinical trials
      at different stages of advancement. This review explores the promising role of
      cathepsin K as a novel antiresorptive for the treatment of osteoporosis. 

PMID- 23957816
TI  - Angiogenesis enhanced by Phyllocaulis boraceiensis mucus in human cells.
AB  - Phyllocaulis boraceiensis mucus is known to be a compound capable of inducing
      cell proliferation and enhancing the wound healing process. The process of
      angiogenesis is a chain of mechanisms responsible for the formation of new
      vessels, which are are involved in cell proliferation, and factors that will act
      in the healing process. Our aim was to demonstrate that the angiogenesis process
      is enhanced in cultures of endothelial cells and fibroblasts treated with P.
      boraceiensis mucus. Experiments were carried out with 10(5) cells.mL(-1) of
      endothelial cells and fibroblasts treated with P. boraceiensis mucus in
      concentrations that have significant effects in proliferation assays, i.e. 0.012
      MUg.MUL(-1) and 0.18 MUg.MUL(-1) , both of which cause extreme responses.
      Aliquots of 100 MUL of cell suspensions were incubated for 1 h at 4  degrees C
      with 1 MUL of antibodies specific for the cell markers vascular endothelial
      growth factor receptor 1 and cluster of differentiation 34, and negative isotype
      controls. Reading and expression analysis of cell markers was performed on a
      FACSCalibur flow cytometer. Expression levels of vascular endothelial growth
      factor receptor 1 and cluster of differentiation 34 expression were significantly
      increased in endothelial cells cultivated with 0.012 MUg.MUL(-1) P. boraceiensis
      mucus, suggesting that this compound is capable of enhancing angiogenesis.

PMID- 23957817
TI  - The influence of executive functions and memory on self-generation benefit in
      persons with multiple sclerosis.
AB  - AIM: Self-generation is a learning strategy, demonstrated to improve learning in
      healthy persons as well as persons with multiple sclerosis (MS). This study
      examines the relative influence of memory performance and executive functioning
      on the ability to benefit from self-generated learning in persons with MS.
      METHOD: Participants consisted of 70 individuals with MS. A within-groups design
      was employed examining recall of words that were presented in two learning
      conditions: (a) a condition in which the to-be-learned information was provided
      to the participant and (b) a condition in which the to-be-learned information was
      self-generated by the participant. Participants were divided into 2 groups based
      on their benefit from self-generation. Participants who benefited from using self
      generation strategy were included in the responders group, and participants who
      did not benefit from using self-generation were included in the nonresponders
      group. Executive functions were assessed with the D-KEFS (Delis-Kaplan Executive
      Function System) Sorting Test, and learning and memory were assessed via the Open
      Trial Selective Reminding Test and the Brief Visual Spatial Memory Test-Revised.
      RESULTS: Responders had significantly better executive functions than
      nonresponders, while no significant differences were noted between the 2 groups
      on memory abilities. Logistic regression analysis revealed that performance on
      the executive functioning task significantly predicted benefit from self
      generation. CONCLUSIONS: Executive functioning is critical for the ability of an
      individual with MS to benefit from self-generation strategy use.

PMID- 23957818
TI  - Anticancer activity and DNA binding of a bifunctional Ru(II) arene aqua-complex
      with the 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine ligand.
AB  - The synthesis and full characterization of the new aqua-complex [(eta(6)-p
      cymene)Ru(OH2)(kappa(2)-N,N-2-pydaT)](BF4)2, [2](BF4)2, and the nucleobase
      derivative [(eta(6)-p-cymene)Ru(9-MeG)(kappa(2)-N,N-2-pydaT)](BF4)2, [4](PF6)2,
      where 2-pydaT = 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine and 9-MeG = 9
      methylguanine, are reported here. The crystal structures of both [4](PF6)2 and
      the chloro complex [(eta(6)-p-cymene)RuCl(kappa(2)-N,N-2-pydaT)](PF6), [1](PF6),
      have been elucidated by X-ray diffraction. The former provided relevant
      information regarding the interaction of the metallic fragment [(eta(6)-p
      cymene)Ru(kappa(2)-N,N-2-pydaT)](2+) and a simple model of DNA. NMR and kinetic
      absorbance studies have proven that the aqua-complex [2](BF4)2 binds to the N7
      site of guanine in nucleobases, nucleotides, or DNA. A stable bifunctional
      interaction (covalent and partially intercalated) between the [(eta(6)-p
      cymene)Ru(kappa(2)-N,N-2-pydaT)](2+) fragment and CT-DNA has been corroborated by
      kinetic, circular dichroism, viscometry, and thermal denaturation experiments.
      The reaction mechanism entails the very fast formation of the Ru-O-(PO3) linkage
      prior to the fast intercalation of the 2-pydaT fragment. Then, a Ru-N7-(G)
      covalent bond is formed at the expense of the Ru-O-(PO3) bond, yielding a
      bifunctional complex. The dissociation rate of the intercalated fragment is slow,
      and this confers additional interest to [2](BF4)2 in view of the likely
      correlation between slow dissociation and biological activity, on the assumption
      that DNA is the only biotarget. Furthermore, [2](BF4)2 displays notable pH
      dependent cytotoxic activity in human ovarian carcinoma cells (A2780, IC50 = 11.0
      MUM at pH = 7.4; IC50 = 6.58 MUM at pH = 6.5). What is more, complex [2](BF4)2 is
      not cross-resistant with cisplatin, exhibiting a resistance factor, RF(A2780cis),
      of 0.28, and it shows moderate selectivity toward the cancer cell lines, in
      particular, A2780cis (IC50 = 3.0 5 +/- 0.08 MUM), relative to human lung
      fibroblast cells (MRC-5; IC50 = 24 MUM), the model for healthy cells. 

PMID- 23957819
TI  - Emerging treatments for chronic constipation.
AB  - INTRODUCTION: Chronic constipation (CC) is a common problem worldwide and, for
      some sufferers, a cause of considerable morbidity. Recent definitions of CC have
      moved from the former emphasis on stool frequency alone to a broader concept that
      strives to encompass the various symptoms that may bother afflicted individuals.
      Accordingly, new therapies attempt to not only increase frequency of defecation
      but also to address such symptoms as satisfaction with bowel action, straining,
      bloating, and distension. AREAS COVERED: To provide context the relative merits
      and problems related to conventional laxative-based approaches to constipation
      are first reviewed and then more recent novel pharmacological approaches to the
      management of constipation assessed. The focus is on two classes of compounds,
      selective prokinetics and prosecretory agents, and studies on their efficacy and
      safety in chronic idiopathic constipation were retrieved and evaluated. EXPERT
      OPINION: While undoubtedly effective, high-quality evidence to support laxatives,
      the traditional remedies for constipation, is remarkably scarce due, in large
      part, to the absence, until very recently, of high-quality randomized controlled
      clinical trials. The selective prokinetic agent prucalopride and the prosecretory
      agents lubiprostone and linaclotide have shown efficacy and been associated with
      a good safety record in large well-conducted clinical studies. Other novel
      approaches, such as the inhibition of ileal bile salt absorption, offer
      particular promise.

PMID- 23957820
TI  - Mapping polymerization and allostery of hemoglobin S using point mutations.
AB  - Hemoglobin is a complex system that undergoes conformational changes in response
      to oxygen, allosteric effectors, mutations, and environmental changes. Here, we
      study allostery and polymerization of hemoglobin and its variants by application
      of two previously described methods: (i) AllosMod for simulating allostery
      dynamics given two allosterically related input structures and (ii) a machine
      learning method for dynamics- and structure-based prediction of the mutation
      impact on allostery (Weinkam et al. J. Mol. Biol. 2013, 425, 647-661), now
      applicable to systems with multiple coupled binding sites, such as hemoglobin.
      First, we predict the relative stabilities of substates and microstates of
      hemoglobin, which are determined primarily by entropy within our model. Next, we
      predict the impact of 866 annotated mutations on hemoglobin's oxygen binding
      equilibrium. We then discuss a subset of 30 mutations that occur in the presence
      of the sickle cell mutation and whose effects on polymerization have been
      measured. Seven of these HbS mutations occur in three predicted druggable binding
      pockets that might be exploited to directly inhibit polymerization; one of these
      binding pockets is not apparent in the crystal structure, but only in structures
      generated by AllosMod. For the 30 mutations, we predict that mutation-induced
      conformational changes within a single tetramer tend not to significantly impact
      polymerization; instead, these mutations more likely impact polymerization by
      directly perturbing a polymerization interface. Finally, our analysis of
      allostery allows us to hypothesize why hemoglobin evolved to have multiple
      subunits and a persistent low frequency sickle cell mutation. 

PMID- 23957821
TI  - The co-development of looking dynamics and discrimination performance.
AB  - The study of looking dynamics and discrimination form the backbone of
      developmental science and are central processes in theories of infant cognition.
      Looking dynamics and discrimination change dramatically across the 1st year of
      life. Surprisingly, developmental changes in looking and discrimination have not
      been studied together. Recent simulations of a dynamic neural field (DNF) model
      of infant looking and memory suggest that looking and discrimination do change
      together over development and arise from a single neurodevelopmental mechanism.
      We probed this claim by measuring looking dynamics and discrimination along
      continuous, metrically organized dimensions in 5-, 7-, and 10-month-old infants
      (N = 119). The results showed that looking dynamics and discrimination changed
      together over development and are linked within individuals. Quantitative
      simulations of a DNF model provide insights into the processes that underlie
      developmental change in looking dynamics and discrimination. Simulation results
      support the view that these changes might arise from a single neurodevelopmental
      mechanism.

PMID- 23957822
TI  - Mexican-origin parents' latent occupational profiles: associations with parent
      youth relationships and youth aspirations.
AB  - This study used an ecological, person-centered approach to identify subgroups of
      families who had similar profiles across multiple dimensions of Mexican-origin
      mothers' and fathers' occupational characteristics (i.e., self-direction,
      hazardous conditions, physical activity) and to relate these subgroups to
      families' sociocultural characteristics and youth adjustment. The study included
      160 dual-earner Mexican-origin families from the urban Southwest. Mothers' and
      fathers' objective work characteristics and families' sociocultural
      characteristics were assessed when youth were in early to middle adolescence;
      adjustment was assessed during late adolescence and early adulthood for 2
      offspring in each family. A latent profile analysis identified 3 profiles that
      evidenced distinct patterns of occupational characteristics: a differentiated
      high physical activity profile characterized by high levels of physical activity
      and low levels of self-direction; an incongruent profile characterized by large
      differences between parents on self-direction, hazards, and physical activity;
      and a congruent highly self-directed profile characterized by congruence across
      parents on occupational characteristics. These profiles were linked to
      sociocultural characteristics (i.e., family income, educational attainment, and
      acculturation) and to relational adjustment (i.e., mother- and father-youth
      conflict, father warmth) and educational aspirations. Results are discussed with
      respect to implications of parents' work for youths' future family relationships
      and attainment.

PMID- 23957823
TI  - Fluorescent light-up probe with aggregation-induced emission characteristics for
      alkaline phosphatase sensing and activity study.
AB  - Fluorogens with aggregation-induced emission (AIE) characteristics have attracted
      intensified research interest in biosensing applications, and those with specific
      targeting ability are especially desirable. In this work, we designed and
      synthesized an AIE fluorescent probe by functionalizing a tetraphenylethylene
      (TPE) fluorogen with two phosphate groups (TPE-phos) for the detection of
      alkaline phosphatase (ALP) and its enzymatic activity based on the specific
      interaction between the probe and ALP. The probe is virtually nonfluorescent in
      aqueous media due to good water solubility. In the presence of ALP, the phosphate
      groups are cleaved through enzymatic hydrolysis, yielding a highly fluorescent
      product as a result of activated AIE process. This light-up probe shows excellent
      selectivity toward ALP among a group of proteins. The detection limit is found to
      be 11.4 pM or 0.2 U L(-1) in Tris buffer solution with a linear quantification
      range of 3-526 U L(-1). The assay is also successfully performed in diluted serum
      with a linear range up to 175 U L(-1), demonstrating its potential application in
      clinical analysis of ALP levels in real samples. Furthermore, by conducting
      kinetic analysis of the enzyme using TPE-phos as the substrate, the kinetic
      parameter kcat/KM is determined to be 5.1*10(5) M(-1) s(-1), indicating a high
      efficiency of the substrate.

PMID- 23957824
TI  - The effects of telmisartan alone or in combination with hydrochlorothiazide on
      morning home blood pressure control: the SURGE 2 practice-based study.
AB  - SURGE 2, a large-scale, practice-based study in 10 countries, evaluated the
      effects of telmisartan alone or with hydrochlorothiazide (HCTZ) on morning (06:00
      11:59) home blood pressure (HBP) control. Hypertensive patients (clinic blood
      pressure [BP] >= 140/90 mmHg) received telmisartan 40 or 80 mg either alone or in
      combination with HCTZ 12.5 mg for 8 weeks. Treatment could be adjusted if clinic
      BP remained >= 140/90 mmHg. Clinic BP was measured in the morning prior to
      medication, and seated HBP monitoring was performed, three times per day, 2 days
      per week. A total of 25,882 patients were included (71% were previously using
      antihypertensives). There was a statistically significant (all p < 0.001)
      reduction in mean morning, lunchtime and evening HBP following treatment with
      telmisartan/telmisartan plus HCTZ, and morning HBP control increased from 10.6
      19.8% to 51.1-64.6%. Similar improvements were observed for lunchtime (from 20.6
      26.0% to 57.7-70.5%) and evening (from 21.3-31.4% to 59.0-68.8%). The morning HBP
      response ranged from 62.6-67.5% (systolic BP) and from 81.4-87.0% (diastolic BP).
      Adverse events were reported by 1.2% of patients. Telmisartan alone or with HCTZ
      improved morning HBP control and maintained a smooth HBP profile throughout the
      day in a real-life setting.

PMID- 23957825
TI  - Living status in patients over 85 years of age after TUVRP.
AB  - INTRODUCTION: To evaluate surgical risk and post-operative quality of living
      status in patients over 85 years of age after transurethral vaporization
      resection of the prostate (TUVRP). METHODS: Sixty patients over 85 years of age
      underwent TUVRP were compared with 228 patients less than the age of 80 years.
      Group A was 60 patients greater than 85 years of age, Group B was 137 patients
      from 71 to 79 years of age, and Group C was 91 patients from 60 to 70 years of
      age. RESULTS: In Group A, pre-operative ASA grade was higher than the other two
      groups, compared with Group C, p < 0.01. Operating time was 40.03 +/- 18.90 min,
      compared in the three groups, p > 0.05. Follow-up was obtained in 49 (81.67%)
      patients; of them 10 patients were deaths with a survival time of 22.90 +/- 11.14
      months. In the 39 survivors, post-operative IPSS score was 11.17 +/- 6.9,
      compared with Group B, p > 0.05 and Group C, p < 0.01. Quality of Life (QOL)
      index was 1.11 +/- 0.80, compared with Group B, p < 0.001 and Group C, p < 0.01.
      Barthel Index score in 16 patients was >60 and the score was 82.81 +/- 8.56 pre
      operatively. The patients with >60 were increased to 19 cases and the score was
      improved to 90.93 +/- 7.58 (p < 0.001) in follow-up. CONCLUSION: Surgical risk in
      patients over 85 years of age was higher than patients less than the age of 80
      years. A safety TUVRP could improve their voiding function and activities of
      daily living.

PMID- 23957826
TI  - Detection of Hb H disease genotypes common in northern Thailand by quantitative
      real-time polymerase chain reaction and high resolution melting analyses.
AB  - We used quantitative real-time polymerase chain reaction (qPCR) and high
      resolution melting (HRM) analyses for the detection of the common alpha
      thalassemia (alpha-thal) genotypes in 40 northern Thai Hb H (beta4) patients. The
      alpha(0)-thal [- -(SEA) (Southeast Asian) deletion] was detected by a multiplex
      gap real-time PCR. To determine the alpha(+)-thal, three primer pairs were
      designed. The A-primer pair was used to amplify the 3' terminal DNA sequences of
      the HBA2 gene, and the B-primer pair amplified the 5' flanking region of the HBA1
      gene. The C-primer pair amplified the 3' terminal DNA sequences of the HBA1 gene
      and was used as an internal control. The -alpha(4.2) (leftward) and -alpha(3.7)
      (rightward) deletions were determined by monitoring the absence of PCR
      product(s). The Hb H patients who had a negative PCR result for the A-primer pair
      but positive for the B- and C-primer pairs carried the -alpha(4.2) deletion,
      while the -alpha(3.7) deletion carriers were negative for the A- and B-primer
      pairs. In the case of Hb H with Hb Constant Spring (Hb CS, alpha142, Term->Gln;
      HBA2: c.427T>C), all primer pairs were positive, HRM analysis of the PCR product
      of the A-primer pair was introduced to analyze the Hb CS gene. It can distinguish
      clearly between normal and Hb CS genotypes. The applied methods for the
      determination of the alpha(0)- and alpha(+)-thal genotypes revealed the results
      to be as accurate as conventional gap-PCR and the direct DNA sequencing methods
      but resulted in a much simpler and faster procedure. 

PMID- 23957827
TI  - Triboelectric active sensor array for self-powered static and dynamic pressure
      detection and tactile imaging.
AB  - We report an innovative, large-area, and self-powered pressure mapping approach
      based on the triboelectric effect, which converts the mechanical stimuli into
      electrical output signals. The working mechanism of the triboelectric active
      sensor (TEAS) was theoretically studied by both analytical method and numerical
      calculation to gain an intuitive understanding of the relationship between the
      applied pressure and the responsive signals. Relying on the unique pressure
      response characteristics of the open-circuit voltage and short-circuit current,
      we realize both static and dynamic pressure sensing on a single device for the
      first time. A series of comprehensive investigations were carried out to
      characterize the performance of the TEAS, and high sensitivity (0.31 kPa(-1)),
      ultrafast response time (<5 ms), long-term stability (30,000 cycles), as well as
      low detection limit (2.1 Pa) were achieved. The pressure measurement range of the
      TEAS was adjustable, which means both gentle pressure detection and large-scale
      pressure sensing were enabled. Through integrating multiple TEAS units into a
      sensor array, the as-fabricated TEAS matrix was capable of monitoring and mapping
      the local pressure distribution applied on the device with distinguishable
      spatial profiles. This work presents a technique for tactile imaging and progress
      toward practical applications of nanogenerators, providing potential solutions
      for accomplishment of artificial skin, human-electronic interfacing, and self
      powered systems.

PMID- 23957829
TI  - A new anastomotic leakage model in circular double stapled colorectal anastomosis
      after low anterior rectum resection in pigs.
AB  - BACKGROUND: A high incidence of anastomotic leakage (37.5%) is reported after low
      anterior rectal resection (LAR) and circular double-stapled anastomosis without
      protective ileostoma. Since the pathomechanism of anastomosis leakage is still
      unclear, a suitable animal model would be most desirable. METHODS: The objective
      was to assess the incidence of clinically apparent and inapparent leakage after
      LAR in pigs (n = 20). Endpoints were radiological, clinical, macroscopic, and
      histologic proof of anastomotic leakage on the 9th postoperative day. Integrity
      of anastomosis was assessed by double-contrast barium examination on 9th
      postoperative day. Animals were sacrificed and anastomoses were resected for
      histopathological investigation. In case of earlier clinical apparent anastomotic
      leakage, radiologic double-contrast barium was performed immediately. RESULTS:
      LAR with a circular double-stapled anastomosis without protective ileostoma was
      performed in 20 pigs (m:f = 8:12). Length of resection was 10-20 cm, anastomosis
      was performed 7 cm ab ano. Five animals (25%) developed clinical apparent
      anastomotic leakage (no appetite, fever, inactivity, tachypnea, discomfort, pain)
      between the 6th (n = 1) and 9th (n = 4) postoperative day, proven by double
      contrast barium radiographs. Additionally in 1 animal clinical inapparent
      anastomotic insufficiency was observed radiologically. Total rate of leakage was
      30% (n = 6). These results were confirmed by leucocytosis, low potassium levels,
      in two cases high ALT and AST and local peritonitis in all cases. CONCLUSION:
      Including one additional case of clinical inapparent leakage, total rate of
      anastomotic leakage was 30% (6/20). Thus we managed to establish a new
      experimental model of anastomotic leakage after low rectal resection comparable
      to the human situation.

PMID- 23957830
TI  - Factors associated with smoking among operating engineers.
AB  - Although disparities in smoking prevalence between white collar workers and blue
      collar workers have been documented, reasons for these disparities have not been
      well studied. The objective of this study was to determine variables associated
      with smoking among Operating Engineers, using the Health Promotion Model as a
      guide. With cross-sectional data from a convenience sample of 498 Operating
      Engineers, logistic regression was used to determine personal and health
      behaviors associated with smoking. Approximately 29% of Operating Engineers
      currently smoked cigarettes. Multivariate analyses showed that younger age,
      unmarried, problem drinking, physical inactivity, and a lower body mass index
      were associated with smoking. Operating Engineers were at high risk of smoking,
      and smokers were more likely to engage in other risky health behaviors, which
      supports bundled health behavior interventions.

PMID- 23957828
TI  - The TWEAK-Fn14 system as a potential drug target.
AB  - Fibroblast growth factor-inducible 14 (Fn14) is a member of the tumour necrosis
      factor (TNF) receptor family that is induced in a variety of cell types in
      situations of tissue injury. Fn14 becomes activated by TNF-like weak inducer of
      apoptosis (TWEAK), a typical member of the TNF ligand family. TWEAK is
      constitutively expressed by monocytes and some tumour cell lines and also shows
      cytokine inducible expression in various other cell types. Fn14 activation
      results in stimulation of signalling pathways culminating in the activation of
      NFkappaB transcription factors and various MAPKs but might also trigger the
      PI3K/Akt pathway and GTPases of the Rho family. In accordance with its tissue
      damage-associated expression pattern and its pleiotropic proinflammatory
      signalling capabilities, the TWEAK-Fn14 system has been implicated in a huge
      number of pathologies. The use of TWEAK- and Fn14-knockout mice identified the
      TWEAK-Fn14 system as a crucial player in muscle atrophy, cerebral ischaemia,
      kidney injury, atherosclerosis and infarction as well as in various autoimmune
      scenarios including experimental autoimmune encephalitis, rheumatoid arthritis
      and inflammatory bowel disease. Moreover, there is increasing preclinical
      evidence that Fn14 targeting is a useful option in tumour therapy. Based on a
      discussion of the signalling capabilities of TWEAK and Fn14, this review is
      focused on two major issues. On the one hand, on the molecular and cellular basis
      of the TWEAK/Fn14-related pathological outcomes in the aforementioned diseases
      and on the other hand, on the preclinical experience that have been made so far
      with TWEAK and Fn14 targeting drugs. 

PMID- 23957831
TI  - Comparison of caregiver forces required for sliding a patient up in bed using an
      array of slide sheets.
AB  - This study investigated the forces required while performing the common patient
      handling task of moving a patient up in bed using traditional cotton sheets or
      friction-reducing slide sheets. Twenty-nine healthy adult participants 18 to 36
      years of age were recruited as "patients." Hand forces and lumbar compression and
      shear forces were calculated on the "caregiver" when performing the repositioning
      task. Significant differences in lumbar compression and lumbar sagittal shear
      forces at L4-L5 and at L5-S1 were found among the three sheet types. No
      difference in peak sum hand force was found between the slide sheets; however,
      the traditional cotton sheet created the greatest force at the hands and every
      sheet exceeded the recommended summative hand force of 35 pounds. As such,
      sliding patients up in bed may contribute to increased risk of musculoskeletal
      injuries in caregivers.

PMID- 23957832
TI  - Occupational back pain among rehabilitation nurses in Saudi Arabia: the influence
      of knowledge and awareness.
AB  - Occupational low back pain among nurses has been the subject of research studies
      worldwide. However, evidence of the influence of nurses' awareness of safe
      handling practices and compliance with standard guidelines on low back pain
      remains scarce. This study examined the association between occupational low back
      pain and level of awareness of back care, and described the self-reported nature
      of low back pain in relation to organizational policies among nurses in Saudi
      Arabia. A total of 155 nurses working in a rehabilitation hospital participated
      in the study. The lack of a patient handling policy at the workplace was
      identified as a significant risk factor for the development of low back pain,
      whereas exercising regularly was a protective factor. Not only mechanical
      exposure but also organizational factors and level of awareness were related to
      the development of low back pain. This study highlights the need to develop
      institutional plans for injury reporting, and provides evidence of the importance
      of incorporating awareness as part of prevention strategies.

PMID- 23957833
TI  - Total synthesis and biological evaluation of an antifungal tricyclic o-hydroxy-p
      quinone methide diterpenoid.
AB  - A convergent route has been developed to synthesize an antifungal tricyclic o
      hydroxy-p-quinone methide diterpenoid and analogues. A Li/naphthalene-mediated
      reductive alkylation was employed for coupling beta-cyclocitral and the
      corresponding benzyl chloride, while a BBr3-mediated one-pot bis-demethylation
      and intramolecular Friedel-Crafts alkylation was used to assemble the tricyclic
      molecular skeleton. The structure-activity relationship of the diterpenoid was
      assessed on the basis of antiproliferation assays of the natural product and
      analogues against strains of pathogenic yeasts and filamentous fungi. 

PMID- 23957835
TI  - Extended-spectrum beta-lactamase producing Klebsiella spp. in chicken meat and
      humans: a comparison of typing methods.
AB  - Recently, chicken meat was identified as a plausible source of extended-spectrum
      beta-lactamase (ESBL) -producing Escherichia coli in humans. We investigated the
      relatedness of ESBL-producing Klebsiella spp. in chicken meat and humans.
      Furthermore, we tested the performance of SpectraCell RA((r)) (River
      Diagnostics), a new typing method based on Raman spectroscopy, in comparison with
      multilocus sequence typing (MLST) for Klebsiella pneumoniae. Twenty-seven
      phenotypically and genotypically confirmed ESBL-producing Klebsiella spp.
      isolates were typed with MLST and SpectraCell RA. The isolates derived from
      chicken meat, human rectal swabs and clinical blood cultures. In the 22 ESBL
      producing K. pneumoniae isolates, CTX-M15 was the predominant genotype, found in
      five isolates of human origin and in one chicken meat isolate. With MLST, 16
      different STs were found, including five new STs. Comparing the results of
      SpectraCell RA with MLST, we found a sensitivity of 70.0% and a specificity of
      81.8% for the new SpectraCell RA typing method. Therefore, we conclude that
      SpectraCell RA is not a suitable typing method when evaluating relationships of
      ESBL-producing Klebsiella spp. at the population level. Although no clustering
      was found with isolates of chicken meat and human origin containing the same ESBL
      genes, MLST showed no clustering into distinctive clones of isolates from chicken
      meat and human origin. More studies are needed to elucidate the role of chicken
      meat in the rise of ESBL-producing Klebsiella spp. in humans.

PMID- 23957834
TI  - A plasmid toolkit for cloning chimeric cDNAs encoding customized fusion proteins
      into any Gateway destination expression vector.
AB  - BACKGROUND: Valuable clone collections encoding the complete ORFeomes for some
      model organisms have been constructed following the completion of their genome
      sequencing projects. These libraries are based on Gateway cloning technology,
      which facilitates the study of protein function by simplifying the subcloning of
      open reading frames (ORF) into any suitable destination vector. The expression of
      proteins of interest as fusions with functional modules is a frequent approach in
      their initial functional characterization. A limited number of Gateway
      destination expression vectors allow the construction of fusion proteins from
      ORFeome-derived sequences, but they are restricted to the possibilities offered
      by their inbuilt functional modules and their pre-defined model organism
      specificity. Thus, the availability of cloning systems that overcome these
      limitations would be highly advantageous. RESULTS: We present a versatile cloning
      toolkit for constructing fully-customizable three-part fusion proteins based on
      the MultiSite Gateway cloning system. The fusion protein components are encoded
      in the three plasmids integral to the kit. These can recombine with any purposely
      engineered destination vector that uses a heterologous promoter external to the
      Gateway cassette, leading to the in-frame cloning of an ORF of interest flanked
      by two functional modules. In contrast to previous systems, a third part becomes
      available for peptide-encoding as it no longer needs to contain a promoter,
      resulting in an increased number of possible fusion combinations. We have
      constructed the kit's component plasmids and demonstrate its functionality by
      providing proof-of-principle data on the expression of prototype fluorescent
      fusions in transiently-transfected cells. CONCLUSIONS: We have developed a
      toolkit for creating fusion proteins with customized N- and C-term modules from
      Gateway entry clones encoding ORFs of interest. Importantly, our method allows
      entry clones obtained from ORFeome collections to be used without prior
      modifications. Using this technology, any existing Gateway destination expression
      vector with its model-specific properties could be easily adapted for expressing
      fusion proteins.

PMID- 23957836
TI  - Hypothalamic agouti-related protein expression is affected by both acute and
      chronic experience of food restriction and re-feeding in chickens.
AB  - The central melanocortin system is conserved across vertebrates. However, in
      birds, little is known about how energy balance influences orexigenic agouti
      related protein (AGRP) and anorexigenic pro-opiomelanocortin (POMC) expression,
      despite the fact that commercial food restriction is critical to the efficient
      production of poultry meat. To enable contrasts to be made, in broiler-breeder
      chickens, between levels of food restriction, between birds with the same body
      weight but different feeding experience, and between birds moved from restricted
      feeding to ad lib. feeding for different periods, five groups of hens were
      established between 6 and 12 weeks of age with different combinations of food
      restriction and release from restriction. AGRP and neuropeptide Y expression in
      the basal hypothalamus was significantly increased by chronic restriction but
      only AGRP mRNA levels reflected recent feeding experience: hens at the same body
      weight that had recently been on ad lib. feeding showed lower expression than
      restricted birds. AGRP expression also distinguished between hens released from
      restriction to ad lib. feeding for different periods. By contrast, POMC and
      cocaine- and amphetamine-regulated transcript mRNA levels were not different.
      These results showed that AGRP mRNA not only reflected differences between a
      bird's weight and its potential weight or set point, but also discriminated
      between differing feeding histories of birds at the same body weight. Therefore,
      AGRP expression potentially provides an integrated measure of food intake
      experience and an objective tool to assess a bird's perception of satiety in
      feeding regimes for improved poultry welfare. 

PMID- 23957837
TI  - Prevalence and cost of hemolyzed samples in a large urban emergency department.

PMID- 23957838
TI  - The interventional therapy for diabetic peripheral artery disease.
AB  - BACKGROUND: Diabetic peripheral arterial disease is the main cause of lower limb
      amputation in patients with diabetes. To summarize the technique and experiences
      and evaluate the clinical effects of blood vessel intervention operation on
      diabetic peripheral artery disease. METHODS: 81 patients with diabetic peripheral
      artery disease from October 2007 to September 2011, 81 cases of the observation
      group were treated by balloon PTA. By adopting the Seldinger puncture technology,
      intubation was placed into a cobra catheter or a pig tail artery catheter and
      directed to the ipsilateral lower extremity artery. A guidewire was used to reach
      the lesion part of patients and a long balloon with a diameter of 4-6 mm was used
      to expand the artery with a pressure of 6-10 atm. RESULTS: 81 patients in the
      observation group received the PTA surgery. The technical succesful rate was
      100%, no complication happened. The skin temperature increased after treatment.
      The blood supply improved significantly. The pulsation of the foot dorsal artery
      was strengthened. The numbness and pain symptoms were moderated significantly. We
      observed better results in the observation group in lower limb vessel diameter
      and foot ulceration healing. None of the patients received amputation surgery.
      Its short-term effects were satisfactory. CONCLUSION: PTA is a feasible technique
      for diabetic peripheral artery disease. It has great clinical significance in
      treating diabetic peripheral arterial disease. Although its short-term effects is
      satisfactory, the long-term effects is necessary for follow up.

PMID- 23957839
TI  - Immunohistochemical characterization of polyclonal antibodies against Enteromyxum
      leei and Enteromyxum scophthalmi (Myxozoa: Myxosporea), intestinal parasites of
      fish.
AB  - The enteric myxozoan parasites Enteromyxum leei (Diamant, Lom et Dykova) and
      Enteromyxum scophthalmi Palenzuela, Redondo et Alvarez-Pellitero are responsible
      for high weight loss in infected fish, which leads to subchronic disease and low
      mortality rates in gilthead sea bream (GSB), Sparus aurata L., and to high
      mortality rates in turbot, Psetta maxima (L.). The detection of initial parasite
      stages in histological sections is particularly difficult, but can be simplified
      by means of specific antibodies. Rabbit polyclonal antibodies (pAbs) were raised
      against E. scophthalmi and E. leei, and direct enzyme-linked immunosorbent assay
      (ELISA) and immunohistochemistry were used to characterize their sensitivity and
      specificity. Both pAbs were adsorbed (apAb) with non-infected intestines to avoid
      non-specific labelling of fish tissues and to improve their specificity. The
      highest titre obtained in ELISA was 1: 32 000 for apAb-Eleei and 1:16 000 for
      apAb-Escoph. Working dilutions in immunohistochemistry were 1:1000 for apAb-Eleei
      and 1:8000 for apAb-Escoph. Both apAbs labelled proliferative and sporogonic
      stages with high specificity. apAb-Escoph was very specific, whereas apAb-Eleei
      cross-reacted with Sphaerospora dicentrarchi Sitja-Bobadilla et Alvarez-Pellitero
      and Sphaerospora testicularis Sitja-Bobadilla et Alvarez-Pellitero, suggesting
      the presence of shared antigens. These pAbs stand as new tools for antigenic
      characterization and the diagnosis of both Enteromyxum species. 

PMID- 23957840
TI  - Administration of low-dose epoetin-alpha facilitates adherence to ribavirin in
      triple therapy with pegylated interferon-alpha-2b and telaprevir.
AB  - AIM: Anemia frequently develops in patients given pegylated interferon, ribavirin
      (RBV), telaprevir (TVR) triple therapy and restricts treatment by forcing
      reduction or discontinuation of RBV administration. We investigated whether
      erythropoietin (EPO) could alleviate RBV-induced anemia to help maintain the RBV
      dose during the first 12 weeks, the triple therapy phase. METHODS: Twenty-two
      patients with hepatitis C virus (HCV) genotype 1 were enrolled. Hemoglobin (Hb)
      concentration was measured every week. If Hb reduction from the baseline was 2
      g/dL or more, 12 000 IU of epoetin-alpha was administrated. When further
      reduction (>=3 g/dL) was observed, 24 000 IU of epoetin-alpha was used. Inosine
      triphosphatase (ITPA) single nucleotide polymorphism (rs1127354) was genotyped
      for all patients. RESULTS: Among the 22 patients enrolled in this study, three
      required RBV dose reduction due to anemia, two had to discontinue or reduce TVR
      and RBV due to creatinine elevation. The remaining 17 patients completed the
      treatment during the triple therapy phase without reduction of the RBV dose or
      adverse events attributable to EPO. Regardless of ITPA genotype, Hb decline was
      well controlled by EPO administration, whereas the total EPO dose tended to be
      higher in the CC genotype group. The average adherence to RBV during the triple
      therapy phase was 97.5%. SVR was achieved in 17 patients; two patients had viral
      breakthrough and three patients had relapse of HCV RNA. CONCLUSION: EPO can be a
      favorable alternative to reduction of RBV to facilitate the adherence of patients
      on TVR-based triple therapy.

PMID- 23957841
TI  - A clinicopathologic case study of two patients with pediatric orbital IgG4
      related disease.
AB  - The purpose of this report is to describe the clinical, radiographica, and
      histopathologic findings in two pediatric patients with orbital IgG4-related
      disease.

PMID- 23957842
TI  - Evaluation of inhibitory effect of phlorotannins from Ecklonia cava on
      triglyceride accumulation in adipocyte.
AB  - In the present study, a methanolic extract of Ecklonia cava and its solvent
      partitioned fractions were evaluated for their antiadipogenic effect in 3T3-L1
      adipocytes. One of them, the n-BuOH fraction, effectively reduced lipid
      accumulation and glucose consumption. In addition, the presence of the n-BuOH
      fraction in adipocytes suppressed the regulations of adipogenic transcription
      factors, PPARgamma and SREBP1c, and adipogenic specific genes, FABP4, FABP1, FAS,
      LPL, HSL, and ACS1. Further purification of n-BuOH fractions led to the isolation
      of six phlorotannins (1-6). The six phlorotannins effectively suppressed
      triglyceride accumulation. Comparative analysis showed that lipid accumulation in
      adipocytes was dramatically attenuated in the presence of eckstolonol (4). 

PMID- 23957843
TI  - Cotton GhMPK6a negatively regulates osmotic tolerance and bacterial infection in
      transgenic Nicotiana benthamiana, and plays a pivotal role in development.
AB  - Mitogen-activated protein kinase (MAPK) cascades play important roles in the
      perception of external signals and the generation of suitable responses. Cotton
      (Gossypium hirsutum) is an important fibre-producing and oil-producing crop
      worldwide. However, few MAPKs and their interaction partners have been
      functionally characterized in cotton. In the present study, the group A MAPK G.
      hirsutum (Gh)MPK6a was identified and characterized. GhMPK6a expression can be
      induced through multiple defence-related signal molecules and abiotic and biotic
      stresses. The ectopic expression of GhMPK6a in Nicotiana benthamiana reduced
      drought and salt tolerance, with elevated malondialdehyde content, higher
      reactive oxygen species content and lower abscisic acid content than in wild-type
      plants. Moreover, plants overexpressing GhMPK6a were sensitive to the bacterial
      pathogen Ralstonia solanacearum. Histochemical analysis of beta-glucuronidase
      activity revealed that GhMPK6a showed tissue-specific expression during
      postgermination development, mixed bud differentiation, and pollination. Most
      importantly, GhMPK6a interacts with the upstream MAPK kinase GhMKK4, as shown by
      the use of yeast two-hybrid and bimolecular fluorescence complementation systems,
      compensating for a deficiency of MAPK interaction partners in cotton crops. Taken
      together, these results suggest that GhMPK6a negatively regulates osmotic stress
      and bacterial infection, and plays an important role in developmental processes.
      These results provide useful information for elucidating the roles of MAPK
      cascades in cotton crops. STRUCTURED DIGITAL ABSTRACT: GhMPK6a physically
      interacts with GhMPK4 by two hybrid (View interaction) GhMPK6a and GhMPK4
      physically interact by bimolecular fluorescence complementation (View
      interaction).

PMID- 23957844
TI  - Does Green's Word Memory Test really measure memory?
AB  - This study investigated whether the Multiple Choice, Paired Associates, Free
      Recall, and Long Delayed Free Recall subtests of Green's Word Memory Test (WMT)
      were sensitive to memory impairment after traumatic brain injury (TBI) in 107
      persons who passed performance validity criteria on the same instrument. Whereas
      several of the California Verbal Learning Test-Second Edition indices
      demonstrated a statistically significant correlation with coma duration, and also
      showed statistically significant mean differences between TBI severity groups,
      none of the four WMT memory subtests did so. It is concluded that, although the
      WMT is an excellent performance validity test, it is not sensitive to memory
      impairment after TBI. 

PMID- 23957845
TI  - Ir(III)-catalyzed mild C-H amidation of arenes and alkenes: an efficient usage of
      acyl azides as the nitrogen source.
AB  - Reported herein is the development of the Ir(III)-catalyzed direct C-H amidation
      of arenes and alkenes using acyl azides as the nitrogen source. This procedure
      utilizes an in situ generated cationic half-sandwich iridium complex as a
      catalyst. The reaction takes place under very mild conditions, and a broad range
      of sp(2) C-H bonds of chelate group-containing arenes and olefins are smoothly
      amidated with acyl azides without the intervention of the Curtius rearrangement.
      Significantly, a wide range of reactants of aryl-, aliphatic-, and olefinic acyl
      azides were all efficiently amidated with high functional group tolerance. Using
      the developed approach, Z-enamides were readily accessed with a complete control
      of regio- and stereoselectivity. The developed direct amidation proceeds in the
      absence of external oxidants and releases molecular nitrogen as a single
      byproduct, thus offering an environmentally benign process with wide potential
      applications in organic synthesis and medicinal chemistry. 

PMID- 23957846
TI  - Acoustic bubble removal to enhance SWL efficacy at high shock rate: an in vitro
      study.
AB  - Rate-dependent efficacy has been extensively documented in shock wave lithotripsy
      (SWL) stone comminution, with shock waves (SWs) delivered at a low rate producing
      more efficient fragmentation in comparison to those delivered at high rates.
      Cavitation is postulated to be the primary source underlying this rate
      phenomenon. Residual bubble nuclei that persist along the axis of SW propagation
      can drastically attenuate the waveform's negative phase, decreasing the energy
      which is ultimately delivered to the stone and compromising comminution. The
      effect is more pronounced at high rates, as residual nuclei have less time to
      passively dissolve between successive shocks. In this study, we investigate a
      means of actively removing such nuclei from the field using a low-amplitude
      acoustic pulse designed to stimulate their aggregation and subsequent
      coalescence. To test the efficacy of this bubble removal scheme, model kidney
      stones were treated in vitro using a research electrohydraulic lithotripter. SWL
      was applied at rates of 120, 60, or 30 SW/min with or without the incorporation
      of bubble removal pulses. Optical images displaying the extent of cavitation in
      the vicinity of the stone were also collected for each treatment. Results show
      that bubble removal pulses drastically enhance the efficacy of stone comminution
      at the higher rates tested (120 and 60 SW/min), while optical images show a
      corresponding reduction in bubble excitation along the SW axis when bubble
      removal pulses are incorporated. At the lower rate of 30 SW/min, no difference in
      stone comminution or bubble excitation was detected with the addition of bubble
      removal pulses, suggesting that remnant nuclei had sufficient time for more
      complete dissolution. These results corroborate previous work regarding the role
      of cavitation in rate-dependent SWL efficacy, and suggest that the effect can be
      mitigated via appropriate control of the cavitation environment surrounding the
      stone.

PMID- 23957847
TI  - Analysis of molecular aggregation equilibria using random mixing statistics.
AB  - Aggregation processes in both the gas phase and aqueous solutions are analyzed by
      comparing aggregate size distributions obtained from molecular dynamics
      simulations with analytical predictions pertaining to a nonaggregating random
      mixture. The latter predictions are obtained by using the binomial distribution
      to predict the statistical properties of a uniformly mixed solution containing
      molecules of the same size and concentration as those in the solution of
      interest. Simulations are performed on systems containing neopentane dissolved in
      either methane, aqueous methanol, or aqueous NaI solutions. Comparisons of the
      theoretical and simulation results are used to both classify and quantify the
      influence of intermolecular interactions on such aggregation processes, including
      the equilibrium constants and thermodynamic functions pertaining to the
      partitioning of molecules between the bulk and first coordination shell of
      neopentane. Although the present results are primarily intended to describe and
      illustrate the random mixing analysis strategy, they also imply that neopentane
      has a greater tendency to aggregate with methane in the dense gas phase than with
      either methanol or iodide ions in aqueous solutions. 

PMID- 23957848
TI  - Tannic acid coated gold nanorods demonstrate a distinctive form of endosomal
      uptake and unique distribution within cells.
AB  - One of the primary challenges associated with nanoparticle-dependent biological
      applications is that endosomal entrapment in a physiological environment severely
      limits the desired targeting and functionality of the nanoconstructs. This study
      sought to overcome that challenge through a systematic approach of gold nanorod
      (GNR) functionalization: evaluating the influence of both aspect ratio and
      surface chemistry on targeted cellular internalization rates and preservation of
      particle integrity. Owing to their unique spectral properties and enhanced
      surface area, GNRs possess great potential for the advancement of nanobased
      delivery and imaging applications. However, their ability for efficient
      intracellular delivery while maintaining their specific physiochemical parameters
      has yet to be satisfactorily explored. This study identified that longer and
      positively charged GNRs demonstrated a higher degree of internalization compared
      to their shorter and negative counterparts. Notably, of the four surface
      chemistries explored, only tannic acid resulted in retention of GNR integrity
      following endocytosis into keratinocyte cells, due to the presence of a strong
      protein corona matrix that served to protect the particles. Taken together, these
      results identify tannic acid functionalized GNRs as a potential candidate for
      future development in nanobased biomolecule delivery, bioimaging, and therapeutic
      applications. 

PMID- 23957849
TI  - Partner interdependence and coping with life-threatening illness: the impact on
      dyadic adjustment.
AB  - General systems theory and Bodenmann's theory of dyadic coping (Bodenmann, 1997)
      provided the framework for exploring the impact of life-threatening illness on
      the dyadic relationship. The sample included 193 dyads experiencing the stress of
      treatment by bone-marrow transplantation (BMT) for cancer which had not responded
      to first-line therapies. A prospective design over 12 months included four
      measurements at designated periods in the treatment process. Except for the
      symptom checklist, which was completed only by the recipient, data were obtained
      on each measure from both partners at each time point. The primary outcome was
      dyadic adjustment measured by the Dyadic Adjustment Scale (DAS; Spanier, 1976). A
      general linear mixed model indicated that dyadic adjustment was stable over time
      for BMT recipients and family caregivers; however, caregivers had lower mean
      values on dyadic adjustment than recipients, and higher mean values on negative
      affect. Bayesian path analysis was used to test actor-partner interdependence
      models reflecting the theory of dyadic coping. Models exhibited adequate fit to
      the data and indicated that apart from baseline dyadic adjustment, partner
      related coping had the greatest positive impact on dyadic adjustment over the
      trajectory for both recipients and their caregivers. Limitations in resources for
      health care occurring on a national level have increased the extent of in-home
      care for acutely ill family members, including BMT recipients. This has serious
      implications for the mental health of the caregiver and for the integrity of the
      family system. Mental health assessment and integration of supportive
      interventions would be important in the prevention of secondary psychosocial
      morbidity.

PMID- 23957850
TI  - Mining featured biomarkers associated with prostatic carcinoma based on
      bioinformatics.
AB  - OBJECTIVE: To analyze the differentially expressed genes and identify featured
      biomarkers from prostatic carcinoma. METHODS: The software "Significance Analysis
      of Microarray" (SAM) was used to identify the differentially coexpressed genes
      (DCGs). The DCGs existed in two datasets were analyzed by GO (Gene Ontology)
      functional annotation. RESULTS: A total of 389 DCGs were obtained. By GO
      analysis, we found these DCGs were closely related with the acinus development,
      TGF-beta receptor and signal transduction pathways. Furthermore, five featured
      biomarkers were discovered by interaction analysis. CONCLUSION: These important
      signal pathways and oncogenes may provide potential therapeutic targets for
      prostatic carcinoma.

PMID- 23957851
TI  - Downregulation of ERp57 expression is associated with poor prognosis in early
      stage cervical cancer.
AB  - OBJECTIVE: We investigated the clinical significance of ERp57 in the progression
      of cervical cancer. METHODS: mRNA and protein expression of ERp57 in cervical
      neoplasias were examined. RESULTS: ERp57 mRNA expression was significantly
      decreased in cervical cancers. Immunohistochemistry revealed that ERp57
      expression in 123 cervical cancers was down-regulated compared to cervical
      intraepithelial neoplasias or normal tissues (p < 0.001). Low ERp57 expression
      was significantly associated with worse overall survival (HR = 12.19, p = 0.018).
      CONCLUSIONS: Low ERp57 expression independently predicts a poor outcome for
      patients with cervical cancer, supporting the notion that ERp57 may be a
      promising novel cancer target.

PMID- 23957852
TI  - Beyond burst pressure: initial evaluation of the natural history of the biaxial
      mechanical properties of tissue-engineered vascular grafts in the venous
      circulation using a murine model.
AB  - We previously developed and validated a murine model for investigating neotissue
      formation in tissue-engineered vascular grafts (TEVGs). Herein, we present the
      first longitudinal assessment of both the microstructural composition and the
      mechanical properties of a TEVG through the process of neovessel formation (total
      scaffold degradation). We show that when (poly)glycolic acid-based biodegradable
      scaffolds were used as inferior vena cava interposition grafts in mice, the
      evolving neovessel developed biaxial properties that approached those of the
      native vein within 24 weeks of implantation. Further, we found that these changes
      in biaxial properties related temporally to extracellular matrix production and
      remodeling, including deposition of collagen (types I and III), elastic fibers
      (elastin and fibrillin-1), and glycosaminoglycans in addition to changes in
      matrix metalloproteinase (MMP)-2 and -9 activity. Improving our understanding of
      the mechanobiological principles underlying vascular neotissue formation in TEVGs
      holds great promise for improving the design of TEVGs and enabling us to continue
      the translation of this technology from the bench to the clinic. 

PMID- 23957853
TI  - Effects of magnesium sulfate on heart rate, blood pressure variability and
      baroreflex sensitivity in preeclamptic rats treated with L-NAME.
AB  - OBJECTIVE: Magnesium sulfate is used for the treatment of preeclampsia. This
      study aimed to evaluate effects of magnesium sulfate on heart rate variability
      (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) in
      pregnant rats treated with N(G)-nitro-.-arginine-methyl ester (L-NAME). METHODS:
      Sprague-Dawley rats were randomly divided into four groups: non-pregnancy and
      three pregnant groups. From gestational day 2-12, normal pregnancy group (NOR)
      received sterile water through intravenous injection, LN was injected with L-NAME
      [25 mg/day] to induce preeclampsia, while LNM group was also treated with
      magnesium sulfate at 0.3 g/kg at gestational day 13. HRV, BPV and BRS were
      monitored, and endothelial functions were detected at gestational day 14.
      RESULTS: Rats with treatment of L-NAME showed significantly increased blood
      pressure and endothelin-1 concentration and decreased plasma NO concentration;
      concomitant treatment with magnesium sulfate suppressed blood pressure. Also,
      rats treated with L-NAME and magnesium sulfate underwent lower heart rate
      variability (lower absolute and normalized LF) and higher blood pressure
      variability (lower normalized HF and LF, higher normalized VLF) compared with non
      pregnant or normal pregnant rats, whereas normalized LF of HRV in rats co
      administered magnesium sulfate returned to normal level. Additionally, rats
      treated with L-NAME underwent decreased BRS-SP, BRS-NE, BRS LF and HF, and rats
      with concomitant magnesium sulfate partially reversed the decline (p>0.05) and
      had significantly lower BRS-SP, BRS-NE. CONCLUSION: Sympathetic and
      parasympathetic impairment exist in preeclamptic rats treated with L-NAME.
      Magnesium sulfate may ameliorate alterations in the autonomic nervous system
      noted in preeclampsia.

PMID- 23957854
TI  - The insulin sensitizing effect of topiramate involves KATP channel activation in
      the central nervous system.
AB  - BACKGROUND AND PURPOSE: Topiramate improves insulin sensitivity, in addition to
      its antiepileptic action. However, the underlying mechanism is unknown.
      Therefore, the present study was aimed at investigating the mechanism of the
      insulin-sensitizing effect of topiramate both in vivo and in vitro. EXPERIMENTAL
      APPROACH: Male C57Bl/6J mice were fed a run-in high-fat diet for 6 weeks, before
      receiving topiramate or vehicle mixed in high-fat diet for an additional 6 weeks.
      Insulin sensitivity was assessed by hyperinsulinaemic-euglycaemic clamp. The
      extent to which the insulin sensitizing effects of topiramate were mediated
      through the CNS were determined by concomitant i.c.v. infusion of vehicle or
      tolbutamide, an inhibitor of ATP-sensitive potassium channels in neurons. The
      direct effects of topiramate on insulin signalling and glucose uptake were
      assessed in vivo and in cultured muscle cells. KEY RESULTS: In hyperinsulinaemic
      euglycaemic clamp conditions, therapeutic plasma concentrations of topiramate (~4
      MUg.mL(-1) ) improved insulin sensitivity (glucose infusion rate + 58%). Using 2
      deoxy-D-[(3) H]glucose, we established that topiramate improved the insulin
      mediated glucose uptake by heart (+92%), muscle (+116%) and adipose tissue
      (+586%). Upon i.c.v. tolbutamide, the insulin-sensitizing effect of topiramate
      was completely abrogated. Topiramate did not directly affect glucose uptake or
      insulin signalling neither in vivo nor in cultured muscle cells. CONCLUSION AND
      IMPLICATIONS: In conclusion, topiramate stimulates insulin-mediated glucose
      uptake in vivo through the CNS. These observations illustrate the possibility of
      pharmacological modulation of peripheral insulin resistance through a target in
      the CNS.

PMID- 23957856
TI  - Comment on letter to the editor from S-O Hansson: 'homoeopathy and consumers
      right to know'.

PMID- 23957855
TI  - pH-dependent stability of creatine ethyl ester: relevance to oral absorption.
AB  - Creatine ethyl ester hydrochloride (CEE) was synthesized as a prodrug of creatine
      (CRT) to improve aqueous solubility, gastrointestinal permeability, and
      ultimately the pharmacodynamics of CRT. We used high-performance liquid
      chromatography (HPLC) and proton nuclear magnetic resonance (NMR) to characterize
      the pH-dependent stability of CEE in aqueous solution and compared the
      permeability of CEE to CRT and creatinine (CRN) across Caco-2 human epithelial
      cell monolayers and transdermal permeability across porcine skin. CEE was most
      stable in a strongly acidic condition (half-life = 570 hours at pH 1.0) where it
      undergoes ester hydrolysis to CRT and ethanol. At pH >= 1.0, CEE cyclizes to CRN
      with the logarithm of the first order rate constant increasing linearly with pH.
      Above pH 8.0 (half-life = 23 sec) the rate of degradation was too rapid to be
      determined. The rate of degradation of CEE in cell culture media and simulated
      intestinal fluid (SIF) was a function of pH and correlated well with the
      stability in aqueous buffered solutions. The permeability of CEE across Caco-2
      monolayers and porcine skin was significantly greater than that of CRT or CRN.
      The stability of CEE in acidic media together with its improved permeability
      suggests that CEE has potential for improved oral absorption compared to CRT.

PMID- 23957857
TI  - Transurethral marking incision of the bladder neck: a helpful technique in robot
      assisted laparoscopic radical prostatectomy involving post-transurethral
      resection of the prostate and cancers protruding into the bladder neck.
AB  - BACKGROUND: Bladder neck transection is one of the most difficult procedures for
      robot-assisted laparoscopic radical prostatectomy (RALP), particularly in
      patients who have undergone previous transurethral resection of the prostate (TUR
      P), and in those with large median lobes or prostate cancer protruding into the
      bladder neck. To ensure negative surgical margins and safely preserve the
      ureteral orifices during bladder neck transection, we propose the use of the
      transurethral resectoscope for making the incision in the bladder neck before
      initiating RALP. Thus, we developed a technique for bladder neck transection to
      facilitate this operation in such patients. CASE PRESENTATION: Two Japanese men,
      aged 61 and 63 years, who were diagnosed with prostate cancer, received a
      transurethral marking incision of the bladder neck before starting RALP; prostate
      cancer developed in one patient after TUR-P and the other patient had cancer
      protruding into the bladder neck. A transurethral resectoscope was used to
      closely observe the ureteral orifices and bladder necks; the bladder necks were
      marked to indicate the depth from the mucosa to the muscular layer. During the
      RALP, the bladder necks were dissected to indicate the depth of the marking
      incision. The surgical margins were negative and perioperative complications did
      not occur. The Foley catheters were removed on postoperative day 6, according to
      the usual protocol. No urinary leakage from the anastomosis sites was observed.
      CONCLUSION: This technique, involving the use of an ordinary transurethral
      resectoscope, may be an easy procedure to ensure negative surgical margins,
      safely preserve the ureteral orifices, avoid increasing the bladder neck
      diameter, and achieve a good quality vesicourethral anastomosis that prevents the
      risk of suture-related tissue tears.

PMID- 23957858
TI  - Copper-mediated direct C2-cyanation of indoles using acetonitrile as the cyanide
      source.
AB  - A copper-mediated C2-cyanation of indoles using cheap and commercially available
      acetonitrile as the "nonmetallic" cyanide source was achieved through sequential
      C-C and C-H bond cleavages. The installation of a removable pyrimidyl group on
      the indole nitrogen atom is the key for this C2 selectivity. This approach
      provides a novel and alternative route leading to indole-2-carbonitrile. 

PMID- 23957859
TI  - HBcAg-specific IL-21-producing CD4+ T cells are associated with relative viral
      control in patients with chronic hepatitis B.
AB  - Function exhaustion of specific cytotoxic CD8+ T cell in chronic virus infection
      partly results from the low levels of CD4 help, but the mechanisms by which CD4
      help T cell required to control hepatitis B virus infection are not well
      understood. In this study, we investigated the role of interleukin-21-producing
      CD4+ T cell response in viral control of hepatitis B virus infection. HBcAg
      specific interleukin-21-producing CD4+ T cells in blood were detected in patients
      with hepatitis B virus infection. Patients with acute hepatitis B had greater
      HBcAg-specific interleukin-21-producing CD4+ T cells in blood compared with
      chronic hepatitis B patients, and there was no statistical significance between
      immune active chronic hepatitis B patients and inactive healthy carrier patients
      for these cells, whereas frequencies of these cells negatively correlated with
      HBV DNA levels but positively correlated with HBc18-27-specific IFN-gamma
      producing CD8+ T cells. Moreover, interleukin-21 sustained HBc18-27-specific CD8+
      T cells in vitro, and interleukin-21 production by HBcAg-specific IL-21-producing
      CD4+ T cells of acute hepatitis B patients enhanced IFN-gamma and perforin
      expression by CD8+ T cells from chronic hepatitis B patients. Our results
      demonstrate that HBcAg-specific interleukin-21-producing CD4+ T cell responses
      might contribute to viral control by sustaining CD8+ T cell antiviral function. 

PMID- 23957860
TI  - National Advisory Groups and their role in immunization policy-making processes
      in European countries.
AB  - During the twenty-first century, the development of national immunization
      programmes (NIP) has matured into robust processes where evidence-based
      methodologies and frameworks have increasingly been adopted. A key role in the
      decision-making and recommending processes is played by National Immunization
      Technical Advisory Groups (NITAGs). In a survey performed among European Union
      member states, Norway and Iceland, in February 2013, 85% of the 27 responding
      countries reported having established a NITAG, and of these, 45% have formal
      frameworks in place for the systematic development of vaccination
      recommendations. Independent of whether a formal framework is in place, common
      key factors are addressed by all NITAGs and also in countries without NITAGs. The
      four main factors addressed by all were: disease burden in the country, severity
      of the disease, vaccine effectiveness or efficacy, and vaccine safety at
      population level. Mathematical modelling and cost-effectiveness analyses are
      still not common tools. Differences in the relative weighting of these key
      factors, differences in data or assumptions on country-specific key factors, and
      differences in existing vaccination systems and financing, are likely to be
      reasons for differences in NITAG recommendations, and eventually NIPs, across
      Europe. Even if harmonization of NIPs is presently not a reasonable aim,
      systematic reviews and the development of mathematical/economic models could be
      performed at supranational level, thus sharing resources and easing the present
      work-load of NITAGs. Nevertheless, it has been argued that harmonization would
      ease central purchase of vaccines, thus reducing the price and increasing access
      to new vaccines. 

PMID- 23957862
TI  - Restriction site-associated DNA sequencing generates high-quality single
      nucleotide polymorphisms for assessing hybridization between bighead and silver
      carp in the United States and China.
AB  - Bighead carp (Hypophthalmichthys nobilis) and silver carp (H. molitrix) are
      invasive species and listed as US federally injurious species under the Lacy Act.
      They have established populations in much of the Mississippi River Basin (MRB;
      Mississippi, Illinois, and Missouri rivers) and are capable of producing fertile
      hybrids and complex introgression. Characterizing the composition of this
      admixture requires a large set of high-quality, evolutionarily conserved,
      diagnostic genetic markers to aid in the identification and management of these
      species in the midst of morphological ambiguity. Restriction site-associated DNA
      (RAD) sequencing of 45 barcoded bighead and silver carp from the United States
      and China produced reads that were aligned to the silver carp transcriptome
      yielded 261 candidate single nucleotide polymorphisms (SNPs) with fixed allelic
      differences between the two species. We selected the highest quality 112 SNP loci
      for validation using 194 putative pure-species and F1 hybrids from the MRB and
      putative bighead carp and silver carp pure species from China (Amur, Pearl and
      Yangtze rivers). Fifty SNPs were omitted due to design/amplification failure or
      lack of diagnostic utility. A total of 57 species-diagnostic SNPs conserved
      between carp species in US and Chinese rivers were identified; 32 were annotated
      to functional gene loci. Twenty-seven of the 181 (15%) putative pure species were
      identified as hybrid backcrosses after validation, including three backcrosses
      from the Amur River, where hybridization has not been documented previously. The
      57 SNPs identified through RAD sequencing provide a diagnostic tool to detect
      population admixture and to identify hybrid and pure-species Asian carps in the
      United States and China. 

PMID- 23957861
TI  - Longitudinal transcriptomic dysregulation in the peripheral blood of transgenic
      Huntington's disease monkeys.
AB  - BACKGROUND: Huntington's Disease (HD) is a progressive neurodegenerative disorder
      caused by an expansion in the polyglutamine (polyQ) region of the Huntingtin
      (HTT) gene. The clinical features of HD are characterized by cognitive,
      psychological, and motor deficits. Molecular instability, a core component in
      neurological disease progression, can be comprehensively evaluated through
      longitudinal transcriptomic profiling. Development of animal models amenable to
      longitudinal examination enables distinct disease-associated mechanisms to be
      identified. RESULTS: Here we report the first longitudinal study of transgenic
      monkeys with genomic integration of various lengths of the human HTT gene and a
      range of polyQ repeats. With this unique group of transgenic HD nonhuman primates
      (HD monkeys), we profiled over 47,000 transcripts from peripheral blood collected
      over a 2 year timespan from HD monkeys and age-matched wild-type control monkeys.
      CONCLUSIONS: Messenger RNAs with expression patterns which diverged with disease
      progression in the HD monkeys considerably facilitated our search for transcripts
      with diagnostic or therapeutic potential in the blood of human HD patients,
      opening up a new avenue for clinical investigation.

PMID- 23957863
TI  - Assessment of De Facto Wastewater Reuse across the US: trends between 1980 and
      2008.
AB  - De facto wastewater reuse is the incidental presence of treated wastewater in a
      water supply source. In 1980 the EPA identified drinking water treatment plants
      (DWTPs) impacted by upstream wastewater treatment plant (WWTP) discharges and
      found the top 25 most impacted DWTPs contained between 2% and 16% wastewater
      discharges from upstream locations (i.e., de facto reuse) under average
      streamflow conditions. This study is the first to provide an update to the 1980
      EPA analysis. An ArcGIS model of DWTPs and WWTPs across the U.S. was created to
      quantify de facto reuse for the top 25 cities in the 1980 EPA study. From 1980 to
      2008, de facto reuse increased for 17 of the 25 DWTPs, as municipal flows
      upstream of the sites increased by 68%. Under low streamflow conditions, de facto
      reuse in DWTP supplies ranged from 7% to 100%, illustrating the importance of
      wastewater in sustainable water supplies. Case studies were performed on four
      cities to analyze the reasons for changes in de facto reuse over time. Three of
      the four sites have greater than 20% treated wastewater effluent within their
      drinking water source for streamflow less than the 25th percentile historic flow.

PMID- 23957865
TI  - Serum chemistry, hematologic, and post-mortem findings in free-ranging bobcats
      (Lynx rufus) with notoedric mange.
AB  - Notoedric mange was responsible for a population decline of bobcats ( Lynx rufus
      ) in 2 Southern California counties from 2002-2006 and is now reported to affect
      bobcats in Northern and Southern California. With this study we document clinical
      laboratory and necropsy findings for bobcats with mange. Bobcats in this study
      included free-ranging bobcats with mange (n = 34), a control group of free
      ranging bobcats without mange (n = 11), and a captive control group of bobcats
      without mange (n = 19). We used 2 control groups to evaluate potential anomalies
      due to capture stress or diet. Free-ranging healthy and mange-infected bobcats
      were trapped or salvaged. Animals were tested by serum biochemistry, complete
      blood count, urine protein and creatinine, body weight, necropsy, and assessment
      for anticoagulant rodenticide residues in liver tissue. Bobcats with severe mange
      were emaciated, dehydrated, and anemic with low serum creatinine,
      hyperphosphatemia, hypoglycemia, hypernatremia, and hyperchloremia, and sometimes
      septicemic when compared to control groups. Liver enzymes and leukocyte counts
      were elevated in free-ranging, recently captured bobcats whether or not they were
      infested with mange, suggesting capture stress. Bobcats with mange had lower
      levels of serum cholesterol, albumin, globulin, and total protein due to protein
      loss likely secondary to severe dermatopathy. Renal insufficiency was unlikely in
      most cases, as urine protein:creatinine ratios were within normal limits. A
      primary gastrointestinal loss of protein or blood was possible in a few cases, as
      evidenced by elevated blood urea nitrogen, anemia, intestinal parasitism,
      colitis, gastric hemorrhage, and melena. The prevalence of exposure to
      anticoagulant rodenticides was 100% (n = 15) in bobcats with mange. These
      findings paint a picture of debilitating, multisystemic disease with infectious
      and toxic contributing factors that can progress to death in individuals and
      potential decline in populations.

PMID- 23957864
TI  - Amyloid fiber formation in human gammaD-Crystallin induced by UV-B photodamage.
AB  - gammaD-Crystallin is an abundant structural protein of the lens that is found in
      native and modified forms in cataractous aggregates. We establish that UV-B
      irradiation of gammaD-Crystallin leads to structurally specific modifications and
      precipitation via two mechanisms: amorphous aggregates and amyloid fibers. UV-B
      radiation causes cleavage of the backbone, in large measure near the interdomain
      interface, where side chain oxidations are also concentrated. 2D IR spectroscopy
      and expressed protein ligation localize fiber formation exclusively to the C
      terminal domain of gammaD-Crystallin. The native beta-sandwich domains are not
      retained upon precipitation by either mechanism. The similarities between the
      amyloid forming pathways when induced by either UV-B radiation or low pH suggest
      that the propensity for the C-terminal beta-sandwich domain to form amyloid beta
      sheets determines the misfolding pathway independent of the mechanism of
      denaturation. 

PMID- 23957866
TI  - Transcatheter arterial chemoembolization for hepatocellular carcinoma: Comparison
      of the therapeutic efficacies between miriplatin and epirubicin.
AB  - AIM: The therapeutic efficacy of transcatheter arterial chemoembolization (TACE)
      using miriplatin was evaluated in comparison with that using epirubicin in
      patients with hepatocellular carcinoma (HCC). METHODS: Two hundred and eight-nine
      HCC patients receiving TACE were retrospectively enrolled; none of the patients
      gave a previous TACE history. The short-term therapeutic efficacy was evaluated
      by computed tomography (CT) performed 1 month later. In patients showing TE-4, CT
      and/or magnetic resonance imaging examinations were performed repeatedly and the
      long-term therapeutic efficacy was assessed based on local tumor recurrence.
      RESULTS: After exclusion of 68 patients (CT not performed at 1 month), 97
      patients treated with epirubicin and 124 treated with miriplatin were analyzed.
      The percentage of patients showing TE-4 was 46.8% in the miriplatin-TACE group,
      being significantly higher than that in the epirubicin-TACE group (33.0%). The
      cumulative local recurrence rates at 18 months were 71.2% in the miriplatin-TACE
      group and 43.1% in the epirubicin-TACE group; multivariate analysis revealed
      higher local tumor recurrence rates in the miriplatin-TACE group than in the
      epirubicin-TACE group. CONCLUSION: For HCC patients, although miriplatin-TACE was
      superior to epirubicin-TACE in the short term, it proved inferior to the latter
      in the long term. The merits of TACE using miriplatin should be further
      investigated, because adverse effects appear to be minimal after miriplatin
      administration.

PMID- 23957867
TI  - Automated serial extraction of DNA and RNA from biobanked tissue specimens.
AB  - BACKGROUND: With increasing biobanking of biological samples, methods for large
      scale extraction of nucleic acids are in demand. The lack of such techniques
      designed for extraction from tissues results in a bottleneck in downstream
      genetic analyses, particularly in the field of cancer research. We have developed
      an automated procedure for tissue homogenization and extraction of DNA and RNA
      into separate fractions from the same frozen tissue specimen. A purpose developed
      magnetic bead based technology to serially extract both DNA and RNA from tissues
      was automated on a Tecan Freedom Evo robotic workstation. RESULTS: 864 fresh
      frozen human normal and tumor tissue samples from breast and colon were serially
      extracted in batches of 96 samples. Yields and quality of DNA and RNA were
      determined. The DNA was evaluated in several downstream analyses, and the
      stability of RNA was determined after 9 months of storage. The extracted DNA
      performed consistently well in processes including PCR-based STR analysis,
      HaloPlex selection and deep sequencing on an Illumina platform, and gene copy
      number analysis using microarrays. The RNA has performed well in RT-PCR analyses
      and maintains integrity upon storage. CONCLUSIONS: The technology described here
      enables the processing of many tissue samples simultaneously with a high quality
      product and a time and cost reduction for the user. This reduces the sample
      preparation bottleneck in cancer research. The open automation format also
      enables integration with upstream and downstream devices for automated sample
      quantitation or storage.

PMID- 23957868
TI  - Partnership with industry: AngioDynamics view on the Clinical Research Office of
      the Endourology Society projects.

PMID- 23957873
TI  - Correlation of geographical location with stable isotope values of hydrogen and
      carbon of fatty acids from New Zealand milk and bulk milk powder.
AB  - The aim of this study was to investigate the correlation of delta2H and delta13C
      of bulk milk powder and milk powder fatty acids to their production region. A
      total of 46 milk powder samples from across New Zealand were collected and
      analyzed. Principal component analysis (PCA) showed that the delta2H and delta13C
      of four fatty acids (C4:0, C14:0, C16:0, C18:1) and bulk milk powder were found
      to be correlated with regional production area. Linear discriminant analysis
      (LDA) models were prepared using different combinations of bulk and fatty acid
      delta2H and delta13C. All models were effective in discriminating samples from
      the North and South Islands. The LDA model using just fatty acid delta2H and
      delta13C provided the best separation. Therefore, the isotopic composition of the
      aforementioned fatty acids can be utilized as a good biomarker in milk powder
      that conveys reliable isotopic information to track milk powders to their
      regional origin.

PMID- 23957874
TI  - Effectiveness of groups for adolescents with type 1 diabetes mellitus and their
      parents.
AB  - Peer- and family-based group therapies have been used as separate interventions
      to improve adjustment and self-management among youth with Type 1 diabetes
      mellitus. This study replicates a treatment protocol that combined these two
      types of diabetes management groups, while also using a wait-list control design
      methodology within an outpatient mental health clinic setting. General
      psychosocial and diabetes-related variables were assessed at baseline,
      immediately posttreatment, and 4 months posttreatment. Youths' medical
      information, including metabolic control values, was extracted from medical
      charts for the 6 months prior to baseline and 6 months after treatment ended. At
      4 months posttreatment, parents and youth reported increased parent
      responsibility, and parents reported improved youth diabetes-specific quality of
      life. Although there were no statistically significant changes in hemoglobin A1c
      values and health care utilization frequency from 6 months prior to and 6 months
      posttreatment, other psychosocial changes (i.e., increases in parent
      responsibility and diabetes-specific quality of life) were documented. Therefore,
      this treatment was found to be a promising intervention for use in an outpatient
      clinical setting to aid in improving the psychosocial functioning of youth with
      Type 1 diabetes mellitus.

PMID- 23957872
TI  - Generating cartilage repair from pluripotent stem cells.
AB  - The treatment of degeneration and injury of articular cartilage has been very
      challenging for scientists and surgeons. As an avascular and hypocellular tissue,
      cartilage has a very limited capacity for self-repair. Chondrocytes are the only
      cell type in cartilage, in which they are surrounded by the extracellular matrix
      that they secrete and assemble. Autologous chondrocyte implantation for cartilage
      defects has achieved good results, but the limited resources and complexity of
      the procedure have hindered wider application. Stem cells form an alternative to
      chondrocytes as a source of chondrogenic cells due to their ability to
      proliferate extensively while retaining the potential for differentiation. Adult
      stem cells such as mesenchymal stem cells have been differentiated into
      chondrocytes, but the limitations in their proliferative ability and the
      heterogeneous cell population hinder their adoption as a prime alternative source
      for generating chondrocytes. Human embryonic stem cells (hESCs) are attractive as
      candidates for cell replacement therapy because of their unlimited self-renewal
      and ability for differentiation into mesodermal derivatives as well as other
      lineages. In this review, we focus on current protocols for chondrogenic
      differentiation of ESCs, in particular the chemically defined culture system
      developed in our lab that could potentially be adapted for clinical application. 

PMID- 23957875
TI  - Similarity, agreement, and assumed similarity in proxy end-of-life decision
      making.
AB  - Medical decisions near the end of life are often made by proxies who can be
      inaccurate in their judgments of patient preferences. Given that accuracy in
      surrogate decision making is an important goal in end-of-life decision making,
      and in light of that previously seen levels of accuracy reflect substantial
      disagreement, error, or both, this study examined both relationship and
      individual factors that potentially affect surrogate accuracy. Specifically, this
      study examined similarity, agreement, and assumed similarity-a process whereby
      raters use their own traits and preferences to rate another person-in spousal
      ratings of end-of-life treatment. This study expands on previous research by
      examining the potential influence of relationship factors and assumed similarity
      on end-of-life decision making among a sample of newlyweds. Newly married couples
      (n = 197) completed self and spouse measures of hypothetical end-of-life
      preferences and scales assessing marital satisfaction, personality, and
      attitudes. Results indicate a moderate level of similarity on husband and wife
      self-rated end-of-life treatment preferences (rs = .18-.29) and a moderate level
      of agreement between self and proxy ratings (rs = .17-.41). The largest
      correlations were seen between self ratings and proxy ratings (e.g., husband self
      ratings and husband proxy ratings of wife preferences, rs = .46-.69), reflecting
      strong assumed similarity in proxy ratings. For wives, similarity with husbands
      on a few attitudinal variables (i.e., spirituality, moral strictness, and
      conservatism) influenced proxy accuracy. Recognizing the potential impact of
      personal preferences on proxy ratings, as well as the potential influence of
      relationship factors, may help improve proxy accuracy and end-of-life care for
      patients and families.

PMID- 23957876
TI  - Social control and smoking: examining the moderating effects of different
      dimensions of relationship quality.
AB  - A common form of social regulation of an individual's health behavior is social
      control. The contextual model of social control assumes that higher relationship
      quality goes along with more beneficial effects of social control on health
      behavior. This study examined potential differential moderating effects of
      different dimensions of relationship quality on the associations between positive
      and negative social control and smoking behavior and hiding smoking. The sample
      consisted of 144 smokers (n = 72 women; mean age = 31.78, SD = 10.04) with a
      nonsmoking partner. Positive and negative social control, dimensions of
      relationship quality consensus, cohesion and satisfaction, numbers of cigarettes
      smoked (NCS), hiding smoking (HS), and control variables were assessed at
      baseline. Four weeks later NCS and HS were assessed again. Only for smokers with
      high consensus, but not cohesion and satisfaction, a negative association between
      positive control and NCS emerged. Moreover, smokers with high consensus tended to
      report more HS when being positively and negatively socially controlled. This
      also emerged for cohesion and positive control. Satisfaction with the
      relationship did not display any interaction effects. This study's results
      emphasize the importance of differentiating not only between positive and
      negative social control but also between different dimensions of relationship
      quality in order to gain a comprehensive understanding of the dynamics in
      romantic dyads with regard to social regulation of behavioral change.

PMID- 23957877
TI  - Ultrasonic-assisted synthesis of surface-clean TiB2 nanoparticles and their
      improved dispersion and capture in Al-matrix nanocomposites.
AB  - Metal-matrix nanocomposites (MMNCs) have great potential for a wide range of
      applications. To provide high performance, effective nanoparticle (NP) dispersion
      in the liquid and NP capture within the metal grains during solidification is
      essential. In this work, we present the novel synthesis and structural
      characterization of surface-clean titanium diboride (TiB2) NPs with an average
      particle size of 20 nm, by ultrasonic-assisted reduction of fluorotitanate and
      fluoroboride salts in molten aluminum. The high-intensity ultrasonic field
      restricts NP growth. Using a master nanocomposite approach, the as-prepared TiB2
      NPs are effectively incorporated into A206 alloys during solidification
      processing because of their clean surface, showing partial capture and
      significant grain refinement. 

PMID- 23957878
TI  - Quantum dots incorporated magnetic nanoparticles for imaging colon carcinoma
      cells.
AB  - BACKGROUND: Engineered multifunctional nanoparticles (NPs) have made a tremendous
      impact on the biomedical sciences, with advances in imaging, sensing and
      bioseparation. In particular, the combination of optical and magnetic responses
      through a single particle system allows us to serve as novel multimodal molecular
      imaging contrast agents in clinical settings. Despite of essential medical
      imaging modalities and of significant clinical application, only few
      nanocomposites have been developed with dual imaging contrast. A new method for
      preparing quantum dots (QDs) incorporated magnetic nanoparticles (MNPs) based on
      layer-by-layer (LbL) self-assembly techniques have developed and used for cancer
      cells imaging. METHODS: Here, citrate - capped negatively charged Fe3O4 NPs were
      prepared and coated with positively - charged hexadecyltrimethyl ammonium bromide
      (CTAB). Then, thiol - capped negatively charged CdTe QDs were electrostatically
      bound with CTAB. Morphological, optical and magnetic properties of the
      fluorescent magnetic nanoparticles (FMNPs) were characterized. Prepared FMNPs
      were additionally conjugated with hCC49 antibodies fragment antigen binding (Fab)
      having binding affinity to sialylated sugar chain of TAG-72 region of LS174T
      cancer cells, which was prepared silkworm expression system, and then were used
      for imaging colon carcinoma cells. RESULTS: The prepared nanocomposites were
      magnetically responsive and fluorescent, simultaneously that are useful for
      efficient cellular imaging, optical sensing and magnetic separation. Transmission
      electron microscopy (TEM) and dynamic light scattering (DLS) revealed that the
      particle size is around 50 nm in diameter with inner magnetic core and outer CdTe
      QDs core-shell structure. Cytotoxicity test of prepared FMNPs indicates high
      viability in Vero cells. NPs conjugated with anti cancer antibodies were
      successfully labeled on colon carcinoma cells (LS174) in vitro and showed
      significant specificity to target cells. CONCLUSION: The present report
      demonstrates a simple synthesis of CdTe QDs-Fe3O4 NPs. The surface of the
      prepared FMNPs was enabled simple conjugation to monoclonal antibodies by
      electrostatic interaction. This property further extended their in vitro
      applications as cellular imaging contrast agents. Such labeling of cells with new
      fluorescent-magneto nanoprobes for living detection is of interest to various
      biomedical applications and has demonstrated the potential for future medical
      use.

PMID- 23957879
TI  - Polymerizable ionic liquid with state of the art transport properties.
AB  - The physicochemical properties of diallyldimethylammonium
      bis(trifluoromethanesulfonyl)imide (DADMATFSI) and its binary mixture with LiTFSI
      are presented herein, also showing this novel compound as a polymerizable room
      temperature ionic liquid with excellent transport properties for Li(+) ions. In
      particular, results of pulsed field gradient (PFG)-NMR diffusion experiments and
      impedance measurements show that DADMATFSI exhibits state of the art properties
      of ionic liquids. Similar ionic diffusion coefficients and a similarly high
      conductivity as seen in the benchmark compound N-butyl-N-methylpyrrolidinium
      bis(trifluoromethanesulfonyl)imide (PYR14TFSI) are observed. In accordance, the
      Li transference number in the binary mixture matches the trend seen for PYR14TFSI
      LiTFSI mixtures. In addition to these impressive properties as ionic liquid,
      DADMATFSI was polymerized by UV treatment. The polymerization is demonstrated and
      the ion conducting properties of the resulting gel polymer electrolyte are
      investigated, showing that DADMATFSI can be transformed into an ionogel and may
      have applications where polymerization is desirable. 

PMID- 23957881
TI  - A larger weight reduction is necessary to elicit an increase in adiponectin and a
      decrease in leptin levels.

PMID- 23957880
TI  - Gene-environment and protein-degradation signatures characterize genomic and
      phenotypic diversity in wild Caenorhabditis elegans populations.
AB  - BACKGROUND: Analyzing and understanding the relationship between genotypes and
      phenotypes is at the heart of genetics. Research on the nematode Caenorhabditis
      elegans has been instrumental for unraveling genotype-phenotype relations, and
      has important implications for understanding the biology of mammals, but almost
      all studies, including forward and reverse genetic screens, are limited by
      investigations in only one canonical genotype. This hampers the detection and
      functional analysis of allelic variants, which play a key role in controlling
      many complex traits. It is therefore essential to explore the full potential of
      the natural genetic variation and evolutionary context of the genotype-phenotype
      map in wild C. elegans populations. RESULTS: We used multiple wild C. elegans
      populations freshly isolated from local sites to investigate gene sequence
      polymorphisms and a multitude of phenotypes including the transcriptome, fitness,
      and behavioral traits. The genotype, transcriptome, and a number of fitness
      traits showed a direct link with the original site of the strains. The separation
      between the isolation sites was prevalent on all chromosomes, but chromosome V
      was the largest contributor to this variation. These results were supported by a
      differential food preference of the wild isolates for naturally co-existing
      bacterial species. Comparing polymorphic genes between the populations with a set
      of genes extracted from 19 different studies on gene expression in C. elegans
      exposed to biotic and abiotic factors, such as bacteria, osmotic pressure, and
      temperature, revealed a significant enrichment for genes involved in gene
      environment interactions and protein degradation. CONCLUSIONS: We found that wild
      C. elegans populations are characterized by gene-environment signatures, and we
      have unlocked a wealth of genotype-phenotype relations for the first time.
      Studying natural isolates provides a treasure trove of evidence compared with
      that unearthed by the current research in C. elegans, which covers only a
      diminutive part of the myriad of genotype-phenotype relations that are present in
      the wild.

PMID- 23957882
TI  - Risk factors for preeclampsia: a case-control study.
AB  - OBJECTIVE: To explore the risk factors of preeclampsia and provide information
      for prevention of preeclampsia among obstetrical patients. METHODS: A case
      control study was designed to find the risk factors of preeclampsia among
      obstetrical patients by logistic regression analysis. RESULTS: The risk factors
      for pregnant women were older gestational age, increasing body mass index, living
      in the countryside or small towns, fewer antenatal visits, and cold seasons.
      CONCLUSIONS: Health education should be emphasized to encourage women to have
      children at a relatively younger age and control weight during pregnancy. Special
      measures should be taken to improve the living condition and prenatal care in the
      countryside and small towns.

PMID- 23957883
TI  - Treatment and referral patterns for psoriasis in United Kingdom primary care: a
      retrospective cohort study.
AB  - BACKGROUND: In the UK, referrals to specialists are initiated by general
      practitioners (GPs). Study objectives were to estimate the incidence of diagnosed
      psoriasis in the UK and identify factors associated with GP referrals to
      dermatologists. METHODS: Newly diagnosed patients with psoriasis were identified
      in The Health Improvement Network (THIN) database between 01 July 2007-31 Oct
      2009. Incidence of diagnosed psoriasis was calculated using the number of new
      psoriasis patients in 2008 and the mid-year total patient count for THIN in 2008.
      A nested case-control design and conditional logistic regression were used to
      identify factors associated with referral. RESULTS: Incidence rate of diagnosed
      adult psoriasis in 2008 was 28/10,000 person-years. Referral rate to
      dermatologists was 18.1 (17.3-18.9) per 100 person-years. In the referred cohort
      (N=1,950), 61% were referred within 30 days of diagnosis and their median time to
      referral was 0 days from diagnosis. For those referred after 30 days (39%, median
      time to referral: 5.6 months), an increase in the number of GP visits prior to
      referral increased the likelihood of referral (OR=1.87 95% CI:1.73-2.01). A
      prescription of topical agents such as vitamin D3 analogues 30 days before
      referral increased the likelihood of being referred (OR=4.67 95% CI: 2.78-7.84),
      as did corticosteroids (OR=2.45 95% CI: 1.45-4.07) and tar products (OR=1.95 95%
      CI: 1.02-3.75). CONCLUSIONS: Estimates of the incidence of diagnosed adult
      psoriasis, referral rates to dermatologists, and characteristics of referred
      patients may assist in understanding the burden on the UK healthcare system and
      managing this population in primary and secondary care.

PMID- 23957884
TI  - Kinscapes, timescapes and genescapes: families living with genetic risk.
AB  - This article synthesises recent research examining how families live with genetic
      risk and the processes of genetic decision-making and disclosure among family
      members who have been or are at risk of transmitting a familial genetic
      condition. Its aim is to generate substantive theory that can inform our
      understanding of the interactional processes at work in the distribution of
      mutual knowledge and awareness of genetic risk in families. The article is
      structured around three interrelated concepts. Kinscape refers to the
      constellation of relations and relatedness that are recognised practically;
      timescape to the multiple temporal frames of social relations and their
      transformation and genescape to the constellation of knowledge, belief and
      practice surrounding genetic inheritance. All three concepts are simultaneously
      natural and cultural. Their intersections create the conditions of kinship and
      genetics. 

PMID- 23957886
TI  - Enhanced understanding of predator-prey relationships using molecular methods to
      identify predator species, individual and sex.
AB  - Predator species identification is an important step in understanding predator
      prey interactions, but predator identifications using kill site observations are
      often unreliable. We used molecular tools to analyse predator saliva, scat and
      hair from caribou calf kills in Newfoundland, Canada to identify the predator
      species, individual and sex. We sampled DNA from 32 carcasses using cotton swabs
      to collect predator saliva. We used fragment length analysis and sequencing of
      mitochondrial DNA to distinguish between coyote, black bear, Canada lynx and red
      fox and used nuclear DNA microsatellite analysis to identify individuals. We
      compared predator species detected using molecular tools to those assigned via
      field observations at each kill. We identified a predator species at 94% of
      carcasses using molecular methods, while observational methods assigned a
      predator species to 62.5% of kills. Molecular methods attributed 66.7% of kills
      to coyote and 33.3% to black bear, while observations assigned 40%, 45%, 10% and
      5% to coyote, bear, lynx and fox, respectively. Individual identification was
      successful at 70% of kills where a predator species was identified. Only one
      individual was identified at each kill, but some individuals were found at
      multiple kills. Predator sex was predominantly male. We demonstrate the first
      large-scale evaluation of predator species, individual and sex identification
      using molecular techniques to extract DNA from swabs of wild prey carcasses. Our
      results indicate that kill site swabs (i) can be highly successful in identifying
      the predator species and individual responsible; and (ii) serve to inform and
      complement traditional methods. 

PMID- 23957885
TI  - Elucidating the evolutionary history and expression patterns of nucleoside
      phosphorylase paralogs (vegetative storage proteins) in Populus and the plant
      kingdom.
AB  - BACKGROUND: Nucleoside phosphorylases (NPs) have been extensively investigated in
      human and bacterial systems for their role in metabolic nucleotide salvaging and
      links to oncogenesis. In plants, NP-like proteins have not been comprehensively
      studied, likely because there is no evidence of a metabolic function in
      nucleoside salvage. However, in the forest trees genus Populus a family of NP
      like proteins function as an important ecophysiological adaptation for inter- and
      intra-seasonal nitrogen storage and cycling. RESULTS: We conducted phylogenetic
      analyses to determine the distribution and evolution of NP-like proteins in
      plants. These analyses revealed two major clusters of NP-like proteins in plants.
      Group I proteins were encoded by genes across a wide range of plant taxa while
      proteins encoded by Group II genes were dominated by species belonging to the
      order Malpighiales and included the Populus Bark Storage Protein (BSP) and WIN4
      like proteins. Additionally, we evaluated the NP-like genes in Populus by
      examining the transcript abundance of the 13 NP-like genes found in the Populus
      genome in various tissues of plants exposed to long-day (LD) and short-day (SD)
      photoperiods. We found that all 13 of the Populus NP-like genes belonging to
      either Group I or II are expressed in various tissues in both LD and SD
      conditions. Tests of natural selection and expression evolution analysis of the
      Populus genes suggests that divergence in gene expression may have occurred
      recently during the evolution of Populus, which supports the adaptive maintenance
      models. Lastly, in silico analysis of cis-regulatory elements in the promoters of
      the 13 NP-like genes in Populus revealed common regulatory elements known to be
      involved in light regulation, stress/pathogenesis and phytohormone responses.
      CONCLUSION: In Populus, the evolution of the NP-like protein and gene family has
      been shaped by duplication events and natural selection. Expression data suggest
      that previously uncharacterized NP-like proteins may function in nutrient sensing
      and/or signaling. These proteins are members of Group I NP-like proteins, which
      are widely distributed in many plant taxa. We conclude that NP-like proteins may
      function in plants, although this function is undefined.

PMID- 23957887
TI  - Thermal and structural characteristics of oligo(3-hexylthiophene)s (3HT)n, n = 4
      36.
AB  - This study is concerned with the thermal and structural characteristics of a
      series of precisely defined, monodisperse, regioregular oligo(3-hexylthiophene)s
      (3HT)n of n = 4-36. We find that these model compounds can feature two distinctly
      different solid-state structures, i.e., the more classical polymorph Form I in
      which the hexyl side-chains are not interdigitated and Form II in which they are.
      The thermodynamic equilibrium melting temperatures of these phases differ as much
      as ~180  degrees C, with 116  degrees C for Form II and 298  degrees C for Form
      I. Furthermore, polymorph II featured an enthalpy of melting of ~3 times that of
      Form I and a rate of crystallization that is ~1 order of magnitude lower than
      that of Form I. A crossover of the thermodynamically preferred Form II into the
      kinetically favored Form I is observed at a number of repeat units of 12. In the
      regime 10 <= n <= 21 the oligo(3-hexylthiophene)s could readily be reversibly
      converted from one polymorph to another by appropriate processing treatments. The
      relevance of these findings for the polymeric form (P3HT) is discussed.

PMID- 23957888
TI  - The pathogenic intestinal spirochaete Brachyspira pilosicoli forms a diverse
      recombinant species demonstrating some local clustering of related strains and
      potential for zoonotic spread.
AB  - BACKGROUND: Brachyspira pilosicoli is an anaerobic spirochaete that can colonizes
      the large intestine of many host species. Infection is particularly problematic
      in pigs and adult poultry, causing colitis and diarrhea, but it is also known to
      result in clinical problems in human beings. Despite the economic importance of
      the spirochaete as an animal pathogen, and its potential as a zoonotic agent, it
      has not received extensive study. METHODS: A multilocus sequence typing (MLST)
      method based on the scheme used for other Brachyspira species was applied to 131
      B. pilosicoli isolates originating from different host species and geographical
      areas. A variety of phylogenetic trees were constructed and analyzed to help
      understand the data. RESULTS: The isolates were highly diverse, with 127 sequence
      types and 123 amino acid types being identified. Large numbers (50-112) of
      alleles were present at each locus, with all loci being highly polymorphic. The
      results of Shimodaira-Hasegawa tests identified extensive genetic recombination,
      although the calculated standardized index of association value (0.1568; P
      <0.0005) suggested the existence of some clonality. Strains from different host
      species and geographical origins generally were widely distributed throughout the
      population, although in nine of the ten cases where small clusters of related
      isolates occurred these were from the same geographical areas or
      farms/communities, and from the same species of origin. An exception to the
      latter was a cluster of Australian isolates originating from pigs, chickens and a
      human being, suggesting the likelihood of relatively recent transmission of
      members of this clonal group between species. CONCLUSIONS: The strongly
      recombinant population structure of B. pilosicoli contrasts to the more highly
      clonal population structures of the related species Brachyspira hyodysenteriae
      and Brachyspira intermedia, both of which are specialized enteric pathogens of
      pigs and poultry. The genomic plasticity of B. pilosicoli may help to explain why
      it has been able to adapt to colonize the large intestines of a wider range of
      hosts compared to other Brachyspira species. The identification of a clonal group
      of isolates that had been recovered from different host species, including a
      human being, suggests that zoonotic transmission by B. pilosicoli may occur in
      nature. Evidence for local transmission between the same host species also was
      obtained.

PMID- 23957889
TI  - Dose escalation of accelerated hypofractionated three-dimensional conformal
      radiotherapy (at 3 Gy/fraction) with concurrent vinorelbine and carboplatin
      chemotherapy in unresectable stage III non-small-cell lung cancer: a phase I
      trial.
AB  - BACKGROUND: Accelerated hypofractionated radiotherapy can shorten total treatment
      time and overcome the accelerated repopulation of tumour cells during
      radiotherapy. This therapeutic approach has demonstrated good efficacy in the
      treatment of locally advanced non-small-cell lung cancer (NSCLC). However, the
      optimal fractionation scheme remains uncertain. The purpose of this phase I trial
      was to explore the maximum tolerated dose (MTD) of accelerated hypofractionated
      three-dimensional conformal radiotherapy (3-DCRT) (at 3 Gy/fraction) administered
      in combination with concurrent vinorelbine (NVB) and carboplatin (CBP)
      chemotherapy for unresectable stage III NSCLC. METHODS: Previously untreated
      cases of unresectable stage III NSCLC received accelerated hypofractionated 3
      DCRT, delivered at 3 Gy per fraction, once daily, with five fractions per week.
      The starting dose was 66 Gy and an increment of 3 Gy was utilized. Higher doses
      continued to be tested in patient groups until the emergence of dose-limiting
      toxicity (DLT). The MTD was regarded as the dose that was one step below the dose
      at which DLT occurred. Patients received at least one cycle of a concurrent two
      drug chemotherapy regimen of NVB and CBP. RESULTS: A total of 13 patients were
      enrolled and progressed through three dose escalation groups: 66 Gy, 69 Gy, and
      72 Gy. No treatment-related deaths occurred. The major adverse events included
      radiation oesophagitis, radiation pneumonitis, and neutropenia. Nausea, fatigue,
      and anorexia were commonly observed, although the magnitude of these events was
      typically relatively minor. Among the entire group, four instances of DLT were
      observed, including two cases of grade 3 radiation oesophagitis, one case of
      grade 3 radiation pneumonitis, and one case of grade 4 neutropenia. All of these
      cases of DLT occurred in the 72 Gy group. Therefore, 72 Gy was designated as the
      DLT dose level, and the lower dose of 69 Gy was regarded as the MTD. CONCLUSIONS:
      For unresectable stage III NSCLC 69 Gy (at 3 Gy/fraction) was the MTD of
      accelerated hypofractionated 3-DCRT administered in combination with concurrent
      NVB and CBP chemotherapy. The toxicity of this chemoradiotherapy regimen could be
      tolerated. A phase II trial is recommended to further evaluate the efficacy and
      safety of this regimen.

PMID- 23957890
TI  - R.A. Fisher's gene-centred view of evolution and the Fundamental Theorem of
      Natural Selection.
AB  - The background to R.A. Fisher's enunciation of his Fundamental Theorem of Natural
      Selection in 1930 is traced and the Theorem in its original form explained. It
      can now be seen as the centrepiece of Fisher's introduction of the gene-centred
      approach to evolutionary biology. Although this paper is a sequel to Edwards
      (1994) it is not a review of the recent literature on the Theorem, to which,
      however, reference is made at the end. 

PMID- 23957891
TI  - Thiol-dependent recovery of catalytic activity from oxidized protein tyrosine
      phosphatases.
AB  - Protein tyrosine phosphatases (PTPs) play an important role in the regulation of
      mammalian signal transduction. During some cell signaling processes, the
      generation of endogenous hydrogen peroxide inactivates selected PTPs via
      oxidation of the enzyme's catalytic cysteine thiolate group. Importantly, low
      molecular weight and protein thiols in the cell have the potential to regenerate
      the catalytically active PTPs. Here we examined the recovery of catalytic
      activity from two oxidatively inactivated PTPs (PTP1B and SHP-2) by various low
      molecular weight thiols and the enzyme thioredoxin. All monothiols examined
      regenerated the catalytic activity of oxidized PTP1B, with apparent rate
      constants that varied by a factor of approximately 8. In general, molecules
      bearing low-pKa thiol groups were particularly effective. The biological thiol
      glutathione repaired oxidized PTP1B with an apparent second-order rate constant
      of 0.023 +/- 0.004 M(-1) s(-1), while the dithiol dithiothreitol (DTT) displayed
      an apparent second-order rate constant of 0.325 +/- 0.007 M(-1) s(-1). The enzyme
      thioredoxin regenerated the catalytic activity of oxidized PTP1B at a
      substantially faster rate than DTT. Thioredoxin (2 MUM) converted oxidized PTP1B
      to the active form with an observed rate constant of 1.4 * 10(-3) s(-1). The
      rates at which these agents regenerated oxidized PTP1B followed the order Trx >
      DTT > GSHand comparable values observed at 2 MUM Trx, 4 mM DTT, and 60 mM GSH.
      Various disulfides that are byproducts of the reactivation process did not
      inactivate native PTP1B at concentrations of 1-20 mM. The common biochemical
      reducing agent tris(2-carboxyethyl)phosphine regenerates enzymatic activity from
      oxidized PTP1B somewhat faster than the thiol-based reagents, with a rate
      constant of 1.5 +/- 0.5 M(-1) s(-1). We observed profound kinetic differences
      between the thiol-dependent regeneration of activity from oxidized PTP1B and SHP
      2, highlighting the potential for structural differences in various oxidized PTPs
      to play a significant role in the rates at which low-molecular weight thiols and
      thiol-containing enzymes such as thioredoxin and glutaredoxin return catalytic
      activity to these enzymes during cell signaling events. 

PMID- 23957892
TI  - OXA- and GES-type beta-lactamases predominate in extensively drug-resistant
      Acinetobacter baumannii isolates from a Turkish University Hospital.
AB  - We determined the antibiotic susceptibility and genetic mechanisms of resistance
      in clinical strains of Acinetobacter baumannii from Istanbul, Turkey. A total of
      101 clinical strains were collected between November 2011 and July 2012.
      Antimicrobial susceptibility was performed using the Vitek 2 Compact system and E
      test. Multiplex PCR was used for detecting bla(OXA -51-like), bla(OXA -23-like),
      bla(OXA -40-like) and bla(OXA -58-like) genes. ISAba1, bla(IMP -like), bla(VIM 
      like), bla(GES), bla(VEB), bla(PER -2), aac-3-Ia and aac-6'-Ib and NDM-1 genes
      were detected by PCR and sequencing. By multiplex PCR, all strains were positive
      for bla(OXA -51), 79 strains carried bla(OXA -23) and one strain carried bla(OXA 
      40). bla(OXA -51) and bla(OXA -23) were found together in 79 strains. ISAba1
      element was detected in 81 strains, and in all cases it was found upstream of
      blaOXA -51 . GES-type carbapenemases were found in 24 strains (GES-11 in 16
      strains and GES-22 in 8 strains) while bla(PER -2), bla(VEB -1), bla(NDM -1),
      blaIMP - and blaVIM -type carbapenemases were not observed. Aminoglycoside
      modifying enzyme (aac-3-Ia and aac-6'Ib) genes were detected in 13 and 15
      strains, respectively. Ninety-seven (96%) A. baumannii strains were defined as
      MDR and of these, 98% were extensively drug resistant (sensitive only to
      colistin). Colistin remains the only active compound against all clinical
      strains. As seen in other regions, OXA-type carbapenemases, with or without an
      upstream ISAba1, predominate but GES-type carbapenemases also appear to have a
      significant presence. REP-PCR analysis was performed for molecular typing and all
      strains were collected into 12 different groups. To our knowledge, this is the
      first report of GES-11 and OXA-40 in A. baumannii from Turkey.

PMID- 23957893
TI  - A natural driven membrane process for brackish and wastewater treatment:
      photovoltaic powered ED and FO hybrid system.
AB  - In isolated locations, remote areas, or islands, potable water is precious
      because of the lack of drinking water treatment facilities and energy supply.
      Thus, a robust and reliable water treatment system based on natural energy is
      needed to reuse wastewater or to desalinate groundwater/seawater for provision of
      drinking water. In this work, a hybrid membrane system combining electrodialysis
      (ED) and forward osmosis (FO), driven by renewable energy (solar energy), denoted
      as EDFORD (ED-FO Renewable energy Desalination), is proposed to produce high
      quality water (potable) from secondary wastewater effluent or brackish water. In
      this hybrid membrane system, feedwater (secondary wastewater effluent or
      synthetic brackish water) was drawn to the FO draw solution while the organic and
      inorganic substances (ions, compounds, colloids and particles) were rejected. The
      diluted draw solution was then pumped to the solar energy driven ED. In the ED
      unit, the diluted draw solution was desalted and high-quality water was produced;
      the concentrate was recycled to the FO unit and reused as the draw solution.
      Results show that the water produced from this system contains a low
      concentration of total organic carbon (TOC), carbonate, and cations derived from
      the feedwater; had a low conductivity; and meets potable water standards. The
      water production cost considering the investment for membranes and solar panel is
      3.32 to 4.92 EUR m(-3) (for 300 days of production per year) for a small size
      potable water production system. 

PMID- 23957894
TI  - Toilet training in individuals with Angelman syndrome: a case series.
AB  - OBJECTIVE: To assess if adapted versions of the response restriction toilet
      training protocol, based on the behavioral phenotype of Angelman syndrome (AS),
      were successful in fostering urinary continence in seven individuals with AS.
      METHOD: Data were collected in AB-designs during baseline, training,
      generalization and follow-up. The response restriction protocol was adapted:
      individuals were trained in their natural environment, were prompted to void and
      along with improving continence, the interval between voids was prolonged and
      time-on-toilet decreased. RESULTS: During generalization five individuals had
      less than two accidents and one to six correct voids per day; during baseline
      more accidents and/or less correct voids occurred. In two participants correct
      voids increased, but several accidents still occurred. Three participants
      maintained positive results after 3-18 months. CONCLUSION: Despite their
      intellectual and behavioral challenges, urinary continence can be acquired in AS.
      Several indications of voiding dysfunctions were found; further research is
      indicated.

PMID- 23957895
TI  - Risk indicators of oral health status among young adults aged 18 years analyzed
      by negative binomial regression.
AB  - BACKGROUND: Limited information on oral health status for young adults aged 18
      year-olds is known, and no available data exists in Hong Kong. The aims of this
      study were to investigate the oral health status and its risk indicators among
      young adults in Hong Kong using negative binomial regression. METHODS: A survey
      was conducted in a representative sample of Hong Kong young adults aged 18 years.
      Clinical examinations were taken to assess oral health status using DMFT index
      and Community Periodontal Index (CPI) according to WHO criteria. Negative
      binomial regressions for DMFT score and the number of sextants with healthy gums
      were performed to identify the risk indicators of oral health status. RESULTS: A
      total of 324 young adults were examined. Prevalence of dental caries experience
      among the subjects was 59% and the overall mean DMFT score was 1.4. Most subjects
      (95%) had a score of 2 as their highest CPI score. Negative binomial regression
      analyses revealed that subjects who had a dental visit within 3 years had
      significantly higher DMFT scores (IRR = 1.68, p < 0.001). Subjects who brushed
      their teeth more frequently (IRR = 1.93, p < 0.001) and those with better dental
      knowledge (IRR = 1.09, p = 0.002) had significantly more sextants with healthy
      gums. CONCLUSIONS: Dental caries experience of the young adults aged 18 years in
      Hong Kong was not high but their periodontal condition was unsatisfactory. Their
      oral health status was related to their dental visit behavior, oral hygiene
      habit, and oral health knowledge.

PMID- 23957896
TI  - Availability of HIV prevention and treatment services for people who inject
      drugs: findings from 21 countries.
AB  - BACKGROUND: About a third of the global HIV infections outside sub-Saharan Africa
      are related to injecting drug use (IDU), and this accounts for a growing
      proportion of persons living with HIV. This paper is a response to the need to
      monitor the state of the HIV epidemic as it relates to IDU and the availability
      of HIV treatment and harm reduction services in 21 high epidemic countries.
      METHODS: A data collection form was designed to cover questions on rates of IDU,
      prevalence and incidence of HIV and information on HIV treatment and harm
      reduction services available to people who inject drugs (PWID). National and
      regional data on HIV infection, IDU in the form of reports and journal articles
      were sought from key informants in conjunction with a systematic search of the
      literature. RESULTS: Completed data collection forms were received for 11
      countries. Additional country-specific information was sourced via the literature
      search. The overall proportion of HIV positive PWID in the selected countries
      ranged from 3% in Kazakhstan to 58% in Vietnam. While IDU is relatively rare in
      sub-Saharan Africa, it is the main driver of HIV in Mauritius and Kenya, with
      roughly 47% and 36% of PWID respectively being HIV positive. All countries had
      antiretroviral treatment (ART) available to PWID, but data on service coverage
      were mainly missing. By the end of 2010, uptake of needle and syringe programmes
      (NSP) in Bangladesh, India and Slovakia reached the internationally recommended
      target of 200 syringes per person, while uptake in Kazakhstan, Vietnam and
      Tajikistan reached between 100-200 syringes per person. The proportion of PWID
      receiving opioid substitution therapy (OST) ranged from 0.1% in Kazakhstan to
      32.8% in Mauritius, with coverage of less than 3% for most countries.
      CONCLUSIONS: In order to be able to monitor the impact of HIV treatment and harm
      reduction services for PWID on the epidemic, epidemiological data on IDU and harm
      reduction service provision to PWID needs to be regularly collected using
      standardised indicators.

PMID- 23957897
TI  - A pilot test of motivational oral health promotion with alcohol-dependent
      inpatients.
AB  - OBJECTIVE: Motivational interviewing (MI) is an effective intervention for
      improving health behavior in a number of domains, and evidence suggests that it
      may be useful for promoting oral health. The current pilot study was designed to
      provide initial evidence that, compared with a didactic control intervention, a
      brief MI-based intervention (BMI) delivered by dental practitioners can yield
      greater improvements in oral hygiene, health-care utilization, and health
      outcomes in a population at heightened risk for oral disease. METHOD: Either the
      control intervention or BMI, delivered by a dentist or a dental hygienist, was
      randomly assigned to 60 individuals in inpatient treatment for alcohol-use
      disorders. Data were obtained by self-report and by examination at baseline and 4
      , 12-, and 24-week follow-up assessments. RESULTS: BMI participants reported
      significantly more frequent toothbrushing during follow-up than control
      participants. No other significant effects were found. CONCLUSION: These findings
      indicate that a brief intervention using MI methods can be delivered by dental
      professionals and has potential utility for promoting improved oral hygiene.
      Additional research to investigate and further develop MI's potential for
      promoting oral health appears warranted.

PMID- 23957898
TI  - The relationship between CAM use and adherence to antiretroviral therapies among
      persons living with HIV.
AB  - OBJECTIVE: The use of complementary and alternative medicine (CAM) among people
      living with HIV and AIDS (PLWHA) may undermine other adaptive illness management
      behaviors, such as treatment adherence. The present study tests the hypothesis
      that CAM use is associated with intentional lapses in adherence (e.g.,
      "medication vacations"), perhaps due to negative beliefs about antiretroviral
      therapy (ART). METHOD: Cross-sectional interviews with 116 PLWHA were completed
      using a computerized assessment of self-reported CAM use and ART adherence.
      RESULTS: Almost half of participants used CAM to treat or manage HIV-related
      health concerns in the past month, and 78% had used CAM since being diagnosed
      with HIV. Seventy-one percent of participants endorsed at least one domain of
      intentional nonadherence since starting HIV treatment. As hypothesized, CAM users
      did not differ from nonusers on overall ART adherence. Contrary to hypotheses,
      CAM users were less likely to report taking medication vacations or having
      stopped taking HIV medications without their doctor's approval compared with
      nonusers. CAM intensity was also related to intentional nonadherence, such that
      patients who engaged in more CAM tended to report fewer skipped doses and fewer
      nonprescribed adjustments to their medication regimen in the past month.
      CONCLUSIONS: Findings suggest that PLWHA use CAM as an adjunct to ART and that
      CAM use does not undermine ART adherence. Needed now is longitudinal research to
      determine how a proactive, holistic approach to HIV care interacts with
      conventional HIV treatment over time, and whether CAM use impacts long-term
      quality of life and health outcomes.

PMID- 23957899
TI  - Course of traumatic stress reactions in couples after a burn event to their young
      child.
AB  - OBJECTIVE: This study examines traumatic stress reactions in couples that were
      followed prospectively for 18 months after a burn event to their child. METHOD:
      The participants included 186 mothers and 159 fathers of 198 preschool children.
      Parents' self-reported traumatic stress reactions were measured with the Impact
      of Event Scale (IES). Predictors included parental emotions and the perceived
      life-threatening character of the child's injury. RESULTS: Rates for clinically
      significant symptoms (IES >= 26) decreased from 50% within the first month to 18%
      at 18 months postburn for mothers and from 27% to 6% for fathers. The decline in
      symptoms was not entirely linear. Mothers had higher scores than fathers, but the
      discrepancy in intrusion symptoms among couples diminished over the course of
      time. Early appraisal of life threat and emotions about the burn event were
      significant predictors. CONCLUSIONS: Both mothers and fathers are seriously
      affected by a burn event of their young child. Despite a general decrease over
      time, a subgroup of parents is at risk for chronic symptoms. The results call for
      the integration of prolonged parent support in family centered pediatric burn
      aftercare programs.

PMID- 23957900
TI  - Competence in caregivers of adolescent and young adult childhood brain tumor
      survivors.
AB  - OBJECTIVE: Caregivers of adolescents and young adults (AYA) with complex medical
      conditions, including brain tumor survivors, have protracted and often complex
      roles, yet a gap exists in understanding their perceived competence. The aim of
      this study is to test a hypothesized model based on the theoretical and empirical
      literature: better caregiver health, better survivor health, and better family
      functioning contribute directly to fewer caregiving demands, which in turn
      contribute to greater caregiver competence. METHOD: Telephone interviews using
      structured self-report questionnaires were conducted in this cross-sectional
      study with a sample of 186 caregivers (mothers) of childhood brain tumor
      survivors aged 14-40 years old who live with at least one parent. Structural
      equation modeling (SEM) was used to test the hypothesized model. RESULTS: The
      final SEM model suggests that survivor health and family functioning directly
      predict caregiver competence. Caregiver health indirectly predicts caregiver
      competence through caregiver demands and then family functioning. Family income
      directly predicts family functioning. The model showed adequate fit (CFI = 0.905,
      TFI = 0.880, and RMSEA = 0.081). Overall, the model accounted for 45% of variance
      in caregiver competence. CONCLUSIONS: For this sample of caregivers of AYA with
      medically complex conditions, family functioning and the health of survivors are
      both important to how they evaluate their skills as caregivers. The results of
      this study underscore the crucial role of care models that focus on optimizing
      the health of the survivor, caregiver, and family, along with supporting a family
      centered approach to their care.

PMID- 23957901
TI  - Personality and risk of diabetes in adults: pooled analysis of 5 cohort studies.
AB  - OBJECTIVE: Diabetes is an increasingly important public health concern, but
      little is known about the contribution of psychological factors on diabetes risk.
      We examined whether personality is associated with risk of incident diabetes and
      diabetes-related mortality. METHOD: An individual-participant meta-analysis of
      34,913 adults free of diabetes at baseline (average age 53.7 years, 57% women)
      from 5 prospective cohort studies from the United States and United Kingdom.
      Personality dimensions included extraversion, neuroticism, agreeableness,
      conscientiousness, and openness to experience based on the Five Factor Model.
      RESULTS: During an average follow-up of 5.7 years, 1845 participants became
      diabetic. Of the 5 personality dimensions, only low conscientiousness was
      associated with an elevated diabetes risk (OR = 0.87, 95% CI = 0.82-0.91 per 1
      standard deviation increment in conscientiousness). This association attenuated
      by 60% after adjustment for obesity and by 25% after adjustment for physical
      inactivity. Low conscientiousness was also associated with elevated risk of
      diabetes mortality (HR = 0.72, CI = 0.53-0.98 per 1 standard deviation increment
      in conscientiousness). Other personality traits were not consistently associated
      with diabetes incidence or mortality. CONCLUSIONS: Low conscientiousness-a
      cognitive-behavioral disposition reflecting careless behavior and a lack of self
      control and planning-is associated with elevated risk of diabetes and diabetes
      related mortality. The underlying mechanisms are likely to involve health
      behaviors, such as poor weight management, physical inactivity, and adherence to
      medical management recommendations.

PMID- 23957902
TI  - Promoting the return of lapsed blood donors: a seven-arm randomized controlled
      trial of the question-behavior effect.
AB  - OBJECTIVE: This study tested key variations in the question-behavior effect
      against a control condition or an implementation intention condition on returning
      to give blood among lapsed donors (individuals who had not given blood in the
      past 2 years). DESIGN: At baseline, 7,000 lapsed donors were randomized to 1 of 6
      experimental conditions or to a control condition. Participants in the
      experimental conditions were asked to complete a 6-item postal questionnaire
      assessing intentions only, interrogative intention, moral norm plus intention,
      anticipated regret plus intention, positive self-image plus intention, or
      implementation intentions. OBJECTIVE measures of behavior were obtained 6 and 15
      months later. The frequency of registrations to give blood over the next 6 and 15
      months was measured. RESULTS: Intention-to-treat analysis of the frequency of
      registrations (GENMOD procedure, Poisson distribution) indicated main effects for
      condition (experimental vs. control) at both 6 months, chi2(1) = 4.64, p < .05,
      and 15 months, chi2(1) = 5.88, p < .05. Positive self-image and implementation
      intention interventions outperformed the control condition at 6 months. At 15
      months, standard intention, interrogative intention, and regret plus intention
      conditions showed more frequent registrations compared with control and were just
      as effective as implementation intention formation. Moderation analysis showed
      that the moral norm and positive self-image conditions were significant for first
      time (1 previous donation) but not repeat (2 or more previous donations) donors.
      CONCLUSION: The question-behavior effect can be used to reinvigorate blood
      donation among lapsed donors, and can be as effective as forming implementation
      intentions.

PMID- 23957904
TI  - Physical activity interventions differentially affect exercise task and barrier
      self-efficacy: a meta-analysis.
AB  - OBJECTIVE: Researchers have yet to establish how interventions to increase
      physical activity influence specific self-efficacy beliefs. The current study
      sought to quantify the effect of interventions to increase physical activity
      among healthy adults on exercise task (EXSE) and barrier self-efficacy (BSE) via
      meta-analysis. Intervention characteristics associated with self-efficacy and
      physical activity changes were also identified. METHODS: A systematic database
      search and manual searches through reference lists of related publications were
      conducted for articles on randomized, controlled physical activity interventions.
      Published intervention studies reporting changes in physical activity behavior
      and either EXSE or BSE in healthy adults were eligible for inclusion. RESULTS: Of
      the 1,080 studies identified, 20 were included in the meta-analyses.
      Interventions had a significant effect of g = 0.208, 95% confidence interval (CI)
      [0.027, 0.388], p < .05, on EXSE; g = 0.128, 95% CI [0.05, 0.20], p < .05 on BSE;
      and g = 0.335 95% CI [0.196, 0.475], p < .001, on physical activity. Moderator
      analyses indicated shorter interventions that did not include structured exercise
      sessions effectively increased EXSE and physical activity, whereas long
      interventions improved BSE. Interventions that did not provide support increased
      BSE and physical activity levels. Further, interventions that did not require the
      use of daily exercise logs improved EXSE and physical activity behavior.
      CONCLUSION: Interventions designed to increase physical activity differentially
      influenced EXSE and BSE. EXSE appeared to play a more significant role during
      exercise adoption, whereas BSE was involved in the maintenance of exercise
      behavior. Recommendations are offered for the design of future interventions.

PMID- 23957905
TI  - Pharmacological treatments in ARDS; a state-of-the-art update.
AB  - Despite its high incidence and devastating outcomes, acute respiratory distress
      syndrome (ARDS) has no specific treatment, with effective therapy currently
      limited to minimizing potentially harmful ventilation and avoiding a positive
      fluid balance. Many pharmacological therapies have been investigated with limited
      success to date. In this review article we provide a state-of-the-art update on
      recent and ongoing trials, as well as reviewing promising future pharmacological
      therapies in ARDS. 

PMID- 23957903
TI  - Pain, depression, and fatigue: loneliness as a longitudinal risk factor.
AB  - OBJECTIVE: Pain, depression, and fatigue function as a symptom cluster and thus
      may share common risk factors. Interpersonal relationships clearly influence
      health, suggesting that loneliness may promote the development of the pain,
      depression, and fatigue symptom cluster. We hypothesized that loneliness would be
      related to concurrent symptom cluster levels and increases in symptom cluster
      levels over time. METHOD: We utilized two observational studies with distinct
      longitudinal samples. Study 1 was a sample of cancer survivors and benign
      controls (N = 115) assessed annually for 2 years. Study 2 was a sample of older
      adults caring for a spouse with dementia (caregivers) and non-caregiver controls
      (N = 229) assessed annually for 4 years. Participants completed annual measures
      assessing loneliness, pain, depression, and fatigue. RESULTS: Across both
      samples, lonelier participants experienced more concurrent pain, depression, and
      fatigue and larger increases in symptom cluster levels from one year to the next
      than less lonely participants. Sleep quality did not mediate the results in
      either study. All analyses were adjusted for relevant demographic and health
      variables. CONCLUSIONS: Two longitudinal studies with different populations
      demonstrated that loneliness was a risk factor for the development of the pain,
      depression, and fatigue symptom cluster over time. The current research helps
      identify people most at risk for pain, depression, and fatigue, and lays the
      groundwork for research about their diagnosis and treatment. These data also
      highlight the health risks of loneliness; pain, depression, and fatigue often
      accompany serious illness and place people at risk for poor health and mortality.

PMID- 23957906
TI  - Validation and factorial invariance of children's attraction to physical activity
      (CAPA) scale in Portugal.
AB  - The Children's Attraction to Physical Activity (CAPA) scale assesses interest in
      and attraction to the physical activity (PA) of children of elementary school
      age. The original (25 items) and shorter versions (15 items) of the scale were
      developed and validated with American children. The purpose of this study was to
      cross-validate the shorter version of the CAPA scale for use with Portuguese
      schoolchildren and to examine the invariance of the multidimensional factor
      structure of the scale in two samples. The sample comprised 683 children (7-10
      years) from public primary schools. The sample was divided into calibration and
      cross-validation samples. The scale was translated into Portuguese and underwent
      forward translation, synthesis of the translation and backward translation and
      was then subjected to expert committee review, pretest and reliability
      assessment. Internal consistency for each of the five subscales within the a
      priori 5-factor structure of the CAPA scale was evaluated through Cronbach's
      alpha, followed by a series of confirmatory factor analyses (CFAs) for both the
      calibration and cross-validation samples. The maximum likelihood robust
      estimation method was used. The CFA demonstrated that a 5-factor structural model
      of the Portuguese translation of the CAPA scale was invariant. The construct
      analysed had the same basic meaning and structural and item differences within
      the two samples. The results indicated that the CAPA scale is appropriate for use
      with Portuguese schoolchildren. The availability of a valid and reliable scale
      should enhance opportunities for further understanding of children's involvement
      in PA.

PMID- 23957907
TI  - Personalizing oral anticoagulant treatment in patients with atrial fibrillation.
AB  - For decades, warfarin has remained the standard oral anticoagulation for stroke
      prevention in atrial fibrillation (AF). Three novel oral anticoagulants (NOACs)
      have been recently approved for stroke prevention in non-valvular AF: dabigatran,
      rivaroxaban and apixaban. Better pharmacological and clinical profiles make these
      newcomers a preferable alternative over warfarin. Current AF guidelines do not
      endorse NOACs over warfarin, or one NOAC over another. Indeed, choice of the
      anticoagulation regimen should be personalized based on the relative efficacy and
      safety of different agents across subgroups stratified by thrombotic and bleeding
      risk, as well as on other clinical factors, including anticoagulation control on
      warfarin, drug interactions, compliance and need for coagulation monitoring. This
      review appraises i) the randomized evidence on approved NOACs versus warfarin in
      AF across subgroups stratified by risk factors of stroke and bleeding and by the
      anticoagulation level reached on warfarin; and ii) clinical factors impacting on
      the anticoagulation regimen selection.

PMID- 23957908
TI  - Heart failure with preserved ejection fraction: future directions in medical
      treatment.

PMID- 23957909
TI  - Simultaneous chronoamperometry and piezoelectric microgravimetry determination of
      nitroaromatic explosives using molecularly imprinted thiophene polymers.
AB  - Thin films of conducting molecularly imprinted polymers (MIPs) were prepared for
      simultaneous chronoamperometry (CA) and piezoelectric microgravimetry (PM)
      determination of several explosive nitroaromatic compounds (NTs) including 2,4,6
      trinitrophenol (TNP), 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitrobenzene (TNB),
      and 2,4-dinitrotoluene (DNT). For that, the bis(2,2'-bithienyl)-(4
      aminophenyl)methane 1 functional monomer allowing for pi-pi stacking recognition
      of the NTs was designed and synthesized. Both theoretical DFT calculations at the
      M062X/3-21G* level and experimental fluorescence titrations indicated the 1:1
      stoichiometry of the 1 and NT prepolymerization complexes formed in solutions.
      The NT-templated MIP (MIP-NT) films were deposited by potentiodynamic
      electropolymerization on the Au-coated quartz crystal resonators (Au-QCRs) from
      solutions of 1 and each of the NT templates at the 1-to-NT mole ratio of 1:1. For
      sensing application, the NTs were extracted from the MIP-NT films. Completeness
      of the extraction was confirmed by the presence and absence before and after
      extraction, respectively, of both the XPS peak of the N 1s electrons of the NT
      nitro groups and the DPV peak of electroreduction of the NTs for the MIP-NT.
      Ultimately, the recognition signal was transduced to the analytical signal of
      simultaneous changes of CA cathodic current and PM resonant frequency. The limit
      of detection (LOD) for NTs was in the range of hundreds and tens micromolar for
      CA and PM, respectively. Moreover, selectivity with respect to common
      interferences of the chemosensors was in the range 2.1-4.8, as determined by
      molecular cross-imprinting. 

PMID- 23957910
TI  - A pragmatic approach to the analysis of diets of generalist predators: the use of
      next-generation sequencing with no blocking probes.
AB  - Predicting whether a predator is capable of affecting the dynamics of a prey
      species in the field implies the analysis of the complete diet of the predator,
      not simply rates of predation on a target taxon. Here, we employed the Ion
      Torrent next-generation sequencing technology to investigate the diet of a
      generalist arthropod predator. A complete dietary analysis requires the use of
      general primers, but these will also amplify the predator unless suppressed using
      a blocking probe. However, blocking probes can potentially block other species,
      particularly if they are phylogenetically close. Here, we aimed to demonstrate
      that enough prey sequence could be obtained without blocking probes. In
      communities with many predators, this approach obviates the need to design and
      test numerous blocking primers, thus making analysis of complex community food
      webs a viable proposition. We applied this approach to the analysis of predation
      by the linyphiid spider Oedothorax fuscus in an arable field. We obtained over
      two million raw reads. After discarding the low-quality and predator reads, the
      libraries still contained over 61 000 prey reads (3% of the raw reads; 6% of
      reads passing quality control). The libraries were rich in Collembola,
      Lepidoptera, Diptera and Nematoda. They also contained sequences derived from
      several spider species and from horticultural pests (aphids). Oedothorax fuscus
      is common in UK cereal fields, and the results showed that it is exploiting a
      wide range of prey. Next-generation sequencing using general primers but without
      blocking probes provided ample sequences for analysis of the prey range of this
      spider and proved to be a simple and inexpensive approach. 

PMID- 23957911
TI  - Structural basis for regulation of human glucokinase by glucokinase regulatory
      protein.
AB  - Glucokinase (GCK) is responsible for maintaining glucose homeostasis in the human
      body. Dysfunction or misregulation of GCK causes hyperinsulinemia,
      hypertriglyceridemia, and type 2 diabetes. In the liver, GCK is regulated by
      interaction with the glucokinase regulatory protein (GKRP), a 68 kDa polypeptide
      that functions as a competitive inhibitor of glucose binding to GCK. Formation of
      the mammalian GCK-GKRP complex is stimulated by fructose 6-phosphate and
      antagonized by fructose 1-phosphate. Here we report the crystal structure of the
      mammalian GCK-GKRP complex in the presence of fructose 6-phosphate at a
      resolution of 3.50 A. The interaction interface, which totals 2060 A(2) of buried
      surface area, is characterized by a small number of polar contacts and
      substantial hydrophobic interactions. The structure of the complex reveals the
      molecular basis of disease states associated with impaired regulation of GCK by
      GKRP. It also offers insight into the modulation of complex stability by sugar
      phosphates. The atomic description of the mammalian GCK-GKRP complex provides a
      framework for the development of novel diabetes therapeutic agents that disrupt
      this critical macromolecular regulatory unit. 

PMID- 23957912
TI  - Comparing the genomes of Helicobacter pylori clinical strain UM032 and Mice
      adapted derivatives.
AB  - BACKGROUND: Helicobacter pylori is a Gram-negative bacterium that persistently
      infects the human stomach inducing chronic inflammation. The exact mechanisms of
      pathogenesis are still not completely understood. Although not a natural host for
      H. pylori, mouse infection models play an important role in establishing the
      immunology and pathogenicity of H. pylori. In this study, for the first time, the
      genome sequences of clinical H. pylori strain UM032 and mice-adapted derivatives,
      298 and 299, were sequenced using the PacBio Single Molecule, Real-Time (SMRT)
      technology. RESULT: Here, we described the single contig which was achieved for
      UM032 (1,599,441 bp), 298 (1,604,216 bp) and 299 (1,601,149 bp). Preliminary
      analysis suggested that methylation of H. pylori genome through its restriction
      modification system may be determinative of its host specificity and adaptation.
      CONCLUSION: Availability of these genomic sequences will aid in enhancing our
      current level of understanding the host specificity of H. pylori.

PMID- 23957913
TI  - Recent advances of immunohistochemistry for diagnosis of renal tumors.
AB  - The recent classification of renal tumors has been proposed according to genetic
      characteristics as well as morphological difference. In this review, we summarize
      the immunohistochemical characteristics of each entity of renal tumors. Regarding
      translocation renal cell carcinoma (RCC), TFE3, TFEB and ALK protein expression
      is crucial in establishing the diagnosis of Xp11.2 RCC, renal carcinoma with
      t(6;11)(p21;q12), and renal carcinoma with ALK rearrangement, respectively. In
      dialysis-related RCC, neoplastic cells of acquired cystic disease-associated RCC
      are positive for alpha-methylacyl-CoA racemase (AMACR), but negative for
      cytokeratin (CK) 7, whereas clear cell papillary RCC shows the inverse pattern.
      The diffuse positivity for carbonic anhydrase 9 (CA9) is diagnostic for clear
      cell RCC. Co-expression of CK7 and CA9 is characteristic of multilocular cystic
      RCC. CK7 and AMACR are excellent markers for papillary RCC and mucinous tubular
      and spindle cell carcinoma. CD82 and epithelial-related antigen (MOC31) may be
      helpful in the distinction between chromophobe RCC and renal oncocytoma. WT1 and
      CD57 highlights the diagnosis of metanephric adenoma. The combined panel of PAX2
      and PAX8 may be useful in the diagnosis of metastatic RCC.

PMID- 23957914
TI  - Expression of ECRG4 is associated with lower proliferative potential of
      esophageal cancer cells.
AB  - We have shown that ECRG4 suppressed Fas-induced apoptosis in Jurkat cells. ECRG4
      mRNA expression was ubiquitously detected in normal adult human tissues,
      suggesting that ECRG4 plays a major role in human tissues. ECRG4 mRNA expression
      was down-regulated in tumor cells. Expression of ECRG4 suppressed cell growth. We
      established an anti-ECRG4 monoclonal antibody. Our immunohistochemical analysis
      demonstrated that ECRG4-positive cells tended to be distributed in the region
      that was negative for Ki-67 in esophageal squamous cell carcinoma tissues. There
      was a significant inverse correlation between ECRG4 expression and Ki-67 labeling
      index in esophageal squamous cell carcinoma. This study provides the first
      functional evidence for an association of endogenous expression of ECRG4 with
      cell proliferation. ECRG4 is a candidate tumor suppressor gene that might be
      involved in the proliferation of esophageal squamous cell carcinoma.

PMID- 23957915
TI  - An immunohistochemical study of human platelets using a rabbit antibody against
      H18-K24 of apolipoprotein CIII (HATKTAK).
AB  - H18-K24 of human apolipopotein CIII (Apo CIII) (HATKTAK) is an activator of the
      macromolecular activators of phagocytosis from platelets (MAPPs). Using a rabbit
      antibody against HATKTAK, we performed an immunohistochemical study of human
      platelets. Indirect ELISA showed that this antibody reacts with Apo CIII-derived
      peptides with a C-terminal of HATKTAK, but not with Apo CIII. Immunoelectron
      microscopy revealed that reaction of anti-HATKTAK antibody occurred in the
      pseudopods of activated platelets. In blood coagula produced from the peripheral
      blood and formalin-fixed after various incubation periods, reaction of this
      antibody with platelets appeared rapidly with a peak at 3 to 6 h of incubation,
      and then diminished gradually. Leukocytes in the blood coagula were stained
      strongly positive. In tissue sections, fresh thrombi and hemorrhages with slight
      fibrin formation revealed a positive response of platelets to anti-HATKTAK
      antibody, whereas older ones with leukocytic infiltration, fibrin formation and
      organization did not. In addition to platelets, endothelial cells and leukocytes
      were stained positive by anti-HATKTAK antibody. All of the positive reactions by
      anti-HATKTAK antibody disappeared or diminished by co-incubation with HATKTAK. In
      conclusion, the anti-HATKTAK antibody reveals platelets during the early phase of
      activation.

PMID- 23957916
TI  - Parp-1 deficiency in ES cells promotes invasive and metastatic lesions
      accompanying induction of trophoblast giant cells during tumorigenesis in uterine
      environment.
AB  - Embryonic stem (ES) cells deficient in poly(ADP-ribose) polymerase-1 (Parp-1)
      develop into teratocarcinomas with the appearance of trophoblast giant cells
      (TGCs) when injected subcutaneously into nude mice. Because the uterus is one of
      the original organs in which germ cell tumors develop with induction of
      trophoblast lineage, here we investigated whether Parp-1 deficiency in ES cells
      affects teratocarcinoma formation processes by grafting ES cells into the horns
      of uteri. Teratocarcinomas developed from both wild-type (Parp-1(+/+) ) and Parp
      1(-/-) ES cells. The weights of the tumors derived from Parp-1(-/-) ES cells were
      lower than those of the tumors derived from Parp-1(+/+) ES cells (P < 0.05). The
      Parp-1(-/-) tumors showed the appearance of TGCs. Notably, organ metastasis to
      the lung and liver was observed for the Parp-1(-/-) tumors, but not for the Parp
      1(+/+) tumors (P < 0.05). Invasions were more frequently observed with the Parp
      1(-/-) tumors compared with the Parp-1(+/+) tumors (P < 0.05). Since TGCs are
      known to have invasive properties, the appearance of TGCs may have supported the
      metastatic process. The present findings suggest that loss of Parp-1 during
      teratocarcinoma formation might augment invasive and metastatic properties of the
      tumors in the uterine environment.

PMID- 23957917
TI  - Bile duct carcinoma involving the common channel associated with
      pancreaticobiliary maljunction shows an extension pattern similar to ductal
      carcinoma of the pancreas.
AB  - Biliary tract cancer occurs frequently in patients with pancreaticobiliary
      maljunction (PBM), although no details of its clinicopathological characteristics
      have been reported. Here we describe a case of bile duct (BD) cancer that
      developed in association with PBM. This BD cancer involved the common channel,
      extended to the main pancreatic duct (MPD) via the common channel, and invaded
      the pancreatic parenchyma, where its growth and spread, and features of its
      recurrence, were similar to those of ductal carcinoma of the pancreas. We assumed
      that MPD extension of BD cancer via the common channel was the reason for its
      deep spread to the pancreas, since BD cancer usually spreads along the BD and
      rarely reaches the common channel of the ampulla of Vater. During the follow-up
      of patients with PBM, attention should be paid to involvement of the common
      channel by BD cancer and also to cancer developing silently in the pancreas after
      extrahepatic BD resection. 

PMID- 23957918
TI  - A case of mucinous cholangiocarcinoma showing features of hepatocellular
      carcinoma.

PMID- 23957919
TI  - A rhabdoid-mimicking intrahepatic cholangiocarcinoma.

PMID- 23957920
TI  - Collision lymph node metastasis of rectal and prostate adenocarcinomas.

PMID- 23957921
TI  - Myelosuppression grading of chemotherapies for hematologic malignancies to
      facilitate communication between medical and dental staff: lessons from two cases
      experienced odontogenic septicemia.
AB  - BACKGROUND: Odontogenic diseases can be a risk factor for life-threatening
      infection in patients with hematologic malignancies during chemotherapy that
      induces myelosuppression of variable severity. Previous studies noted the
      necessity of the elimination of all odontogenic foci before hematopoietic stem
      cell transplantation. To enable planning for the adequate dental intervention,
      the oral medicine team must understand the general status of patient and the
      intensity of the chemotherapy, which is sometimes difficult to be fully
      appreciated by dental staff. Therefore, a simplified grading would facilitate the
      sharing of information between hematologists, dentists and oral hygienists. This
      study aimed to introduce our myelosuppression grading of chemotherapies for
      hematologic malignancies and analyze the timing of occurrence of severe
      odontogenic infection. METHODS: 37 patients having received various
      chemotherapies for hematologic malignancies were enrolled. The chemotherapy
      regimens were classified into four grades based on the persistency of
      myelosuppression induced by chemotherapy. Mild myelosuppressive chemotherapies
      were classified as grade A, moderate ones as grade B, severe ones as grade C, and
      chemotherapies that caused severe myelosuppression and persistent
      immunodeficiency (known as conditioning regimens for transplant) as grade D. The
      timing of occurrence of severe odontogenic infection was retrospectively
      investigated. RESULTS: Two patients (5.4%) had severe odontogenic infections
      after grade B or C chemotherapy. One occurred after extraction of non-salvageable
      teeth; the other resulted from advanced periodontitis in a tooth that could not
      be extracted because of thrombocytopenia. Both were de novo hematologic
      malignancy patients. During grade D chemotherapy, no patients had severe
      odontogenic infections. CONCLUSIONS: The simplified grading introduced in this
      study is considered a useful tool for understanding the myelosuppressive state
      caused by chemotherapy and facilitating communication between medical and dental
      staff. During the period around the primary chemotherapy, especially for de novo
      hematologic malignancy patients who often received grade B to C myelosuppression
      chemotherapy, caution should be exercised for severe odontogenic infection by the
      oral medicine team, irrespective of whether invasive treatment is to be
      performed.

PMID- 23957923
TI  - What does absence of lymph node in resected specimen mean after neoadjuvant
      chemoradiation for rectal cancer.
AB  - BACKGROUND: The effect of insufficient node sampling in patients with rectal
      cancer managed by neoadjuvant chemoradiation followed by surgery has not been
      clearly determined. We evalulated the impact of insufficient sampling or even
      abscence of lymph nodes in the specimen on survival in patients at high-risk (T3,
      T4 or node positive) for rectal cancer. METHODS: We conducted a single
      institution, retrospective analysis of all patients who underwent surgical rectal
      resection following neoadjuvant chemoradiation for treatment of mid to lower
      rectal cancer between 1997 and 2009. ypNX was defined as the absence of lymph
      nodes retrieved in the resected specimen. RESULTS: A total of 132 patients
      underwent resection for treatment of rectal cancer following neoadjuvant
      chemoradiation. Ninety four patients (71.2%) were considered as having node
      negative disease, including ypNx and ypN0. In 38 patients (28.8%), the primary
      tumor was associated with regional lymph node metastases (ypNpos). The mean
      number of retrieved nodes per specimen was 14.2, respectively. The five-year
      overall survival from initial operation for the ypNx group was 100%,
      respectively. The estimated five-year overall survival for ypN0 and ypNpos was
      84.0% and 60.3%, respectively (P =0.001). No significant differences in overall
      survival were observed between the ypNx and ypN0 group (P =0.302). CONCLUSION:
      Absence of recovered LN in resected specimens after neoadjuvant chemoradiation
      was observed in 7.6% of specimens. Absence of LN should not be regarded as a risk
      factor for poor survival or as a sign of less radical surgery.

PMID- 23957924
TI  - Partial response after transcatheter arterial infusion chemotherapy in a patient
      with systemic chemotherapy-resistant unresectable colon cancer and hepatic
      metastasis: (case report).
AB  - We report here a case of partial response to hepatic arterial infusion
      chemotherapy in a patient who developed serious hepatic failure due to
      unresectable colorectal cancer and hepatic metastasis and showed resistance to
      systemic chemotherapy with molecular targeted drugs, mFOLFOX6, and FOLFIRI. The
      patient was a 60-year-old woman who underwent sigmoidectomy for sigmoid colon
      cancer, lateral posterior hepatic segmentectomy for metastatic liver cancer, and
      postoperative radiation therapy for metastatic lung cancer. As first-line
      systemic chemotherapy, mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin),
      bevacizumab + FOLFIRI (irinotecan, 5-fluorouracil, leucovorin), and anti
      epidermal growth factor receptor antibody  + irinotecan were administered, in
      that order. However, recurrent hepatic metastasis was exacerbated, which induced
      serious hepatic failure manifested by general malaise, jaundice, abnormal hepatic
      function, difficulty in walking due to bilateral lower extremity edema, and
      decreased appetite. The patient was admitted in a serious condition. After
      hospitalization, the patient received hepatic arterial infusion chemotherapy with
      5-fluorouracil and l-leucovorin. After two complete courses, the symptoms
      improved. The patient's performance status also improved, and she was discharged
      from the hospital. Four months after discharge, the patient had continued
      outpatient chemotherapy and maintained excellent performance status. Although
      HAIC is not presently considered an alternative to systemic chemotherapy, it is
      sometimes effective in patients who show resistance to molecular targeted drug
      therapy, FOLFOX, and FOLFIRI, and in whom hepatic metastasis is a key factor in
      determining prognosis and serious hepatic failure. Further studies should be
      performed in the future to verify these findings.

PMID- 23957926
TI  - Conductive oxygen barrier films using supramolecular assembly of graphene
      embedded polyelectrolyte multilayers.
AB  - The supramolecular self-assembly of polyelectrolyte multilayers (PEMs) provides
      robust bottom-up strategies to assemble a broad spectrum of nanostructures on the
      host substrates. In this study, we discuss the formation of graphene nanoplatelet
      (GNP) embedded polyelectrolyte films to enhance the oxygen barrier properties of
      poly(ethylene terephthalate) (PET) films. Despite cheaper costs and high
      mechanical strength, the diffusion of small gas molecules such as oxygen through
      PET films remains a matter of great concern. The simple yet robust supramolecular
      deposition of GNP/polyelectrolyte on PET substrates significantly increases the
      tortuous path the oxygen molecule has to travel, making it harder to diffuse
      through the PET film. With permeability coefficients in the range of 10-18 cc
      cm/cm(2) s Pa, the coatings developed in this study show three orders of
      magnitude reduction as compared to the permeability coefficient of the bare PET
      film, significantly lower than that of ethylene vinyl alcohol (EVOH) and
      comparable to silicon oxide thin films used in commercial gas barrier foils. The
      use of GNPs in the multilayered films also helped reduce the electrical sheet
      resistance to about 1MOmega which is five orders of magnitude lower than the
      original PET substrate opening up promising opportunities for future use in
      semiconductor and electronics industry. Making suitable modifications in the
      deposition process, three configurations of GNP embedded PEM multilayers namely
      hydrogen bonded, electrostatic, and composite films were developed and their
      effect on oxygen barrier property and sheet resistance was monitored. Oxygen
      permeability of films was tested in accordance with ASTM D-3985 using a MOCON
      2/21 ML instrument, whereas electrical sheet resistance was quantified using a
      Gamry Femtostat Electrochemical Impedance station.

PMID- 23957925
TI  - Toll-like receptor 9 promoter polymorphism is associated with decreased risk of
      Alzheimer's disease in Han Chinese.
AB  - BACKGROUND: Toll-like receptors (TLRs), as major innate immune mediators, may be
      involved in clearance of cerebral amyloid-beta (Abeta) deposits. Recently, a
      novel TLR9 signaling pathway has been uncovered, which is functionally associated
      with the immune inflammatory response and reducing Abeta burden in Alzheimer's
      disease (AD) mice. Therefore, TLR9 might represent a reasonable functional
      candidate gene for AD. FINDINGS: Our study investigated 1,133 sporadic late-onset
      AD (LOAD) and 1,159 healthy controls matched for sex and age in a large Han
      Chinese population. One selected functional rs187084 polymorphism within the TLR9
      gene was genotyped by polymerase chain reaction-ligase detection reaction in a
      case-control associated study. The TLR9 rs187084 variant homozygote GG was
      significantly associated with a decreased LOAD risk after adjusting for age,
      gender, and ApoE epsilon4 status by logistic regression analysis (P = 0.035). Our
      result showed significant evidence of the interaction of ApoE epsilon4 with
      rs187084. When we further stratified our data by the ApoE epsilon4 status, we
      detected significant differences in the genotype and allele distributions of
      rs187084 between LOAD patients and controls in ApoE epsilon4 carriers (P < 0.001,
      P = 0.003, respectively). Moreover, we examined TLR9 expression in peripheral
      blood monocytes by flow cytometry, and the GG genotype of the TLR9 rs187084
      polymorphism was associated with a higher TLR9 expression than two other
      genotypes in LOAD patients. CONCLUSION: Our findings support the hypothesis that
      the TLR9 polymorphism may modify LOAD risk in the Han Chinese population.

PMID- 23957927
TI  - Synthesis and characterization of TiO2 pillared montmorillonites: application for
      methylene blue degradation.
AB  - TiO2 pillared clay composites were prepared by modifying of montmorillonite (Mt)
      with cetyl-trimethyammoniumbromide (CTAB) and then using an acidic solution of
      hydrolyzed Ti alkoxide to intercalate into the interlayer space of the organic
      modified Mt. The as-prepared materials were characterized by XRD, FTIR, TEM, SEM
      TG-DTA, specific surface area and porosity measurements. The composites had a
      porous delaminated structure with pillared fragments and well dispersed TiO2
      nanoparticles. Introduction of CTAB into the synthetic system accelerated the
      hydrolysis and condensation of the Ti source, which promoted TiO2 formation. In
      addition, the CTAB also significantly increased the porosity and surface area of
      the composites. A number of anatase particles, with crystal sizes of 5-10 nm,
      were homogenously distributed on the surface of the Mt as the result of the
      templating role of CTAB. The resultant TiO2 pillared Mt exhibited good thermal
      stability as indicated by its surface area after calcination at 800 degrees C. No
      phase transformations from anatase to rutile were observed even under calcination
      at 900 degrees C. The grain size of the anatase in prepared sample increased from
      2.67 nm to 13.42 nm as the calcination temperature increased from 300 degrees C
      to 900 degrees C. The photocatalytic performance of these new porous materials
      was evaluated by using methylene blue degradation. The composite exhibited better
      photocatalytic property than P 25. The maximum removal efficiency of this
      composite was up to 99% within 60 min.

PMID- 23957928
TI  - Adsorption of cationic and anionic surfactants on natural and synthetic carbonate
      materials.
AB  - Adsorption of cationic and anionic surfactants on carbonate materials is
      investigated in this study. Cetylpyridinium chloride (CPC) and sodium dodecyl
      sulfate (SDS) are chosen as typical cationic and anionic surfactants,
      respectively. It is found that the cationic CPC exhibits negligible adsorption on
      synthetic calcite in deionized water compared with the adsorption of the anionic
      SDS. However, a substantial amount of adsorption of CPC is observed on natural
      carbonates, such as dolomite and limestone. X-ray photoelectron spectroscopy
      (XPS) reveals that that a substantial amount of silicon and aluminum exists in
      natural dolomite and limestone but not in synthetic calcite. The adsorption
      plateau of CPC on carbonates highly depends on the silicon composition in the
      carbonate samples due to the strong electrostatic interaction between CPC and
      negative binding sites in silica and/or clay. The adsorption of CPC on natural
      carbonates is reduced in the presence of 1atm CO2 compared with the case under
      1atm air, while SDS precipitates out of the solution under 1atm CO2 due to its
      intolerance to divalent ions released from the carbonate surface as a result of
      CO2 acidification. 

PMID- 23957930
TI  - Context matters: the structure of task goals affects accuracy in multiple-target
      visual search.
AB  - Career visual searchers such as radiologists and airport security screeners
      strive to conduct accurate visual searches, but despite extensive training,
      errors still occur. A key difference between searches in radiology and airport
      security is the structure of the search task: Radiologists typically scan a
      certain number of medical images (fixed objective), and airport security
      screeners typically search X-rays for a specified time period (fixed duration).
      Might these structural differences affect accuracy? We compared performance on a
      search task administered either under constraints that approximated radiology or
      airport security. Some displays contained more than one target because the
      presence of multiple targets is an established source of errors for career
      searchers, and accuracy for additional targets tends to be especially sensitive
      to contextual conditions. Results indicate that participants searching within the
      fixed objective framework produced more multiple-target search errors; thus,
      adopting a fixed duration framework could improve accuracy for career searchers. 

PMID- 23957931
TI  - Subjective analysis of cold thermal environments.
AB  - The present work is dedicated to the study of cold thermal environments in food
      distribution industrial units through a subjective assessment based on an
      individual questionnaire which aims to describe the working conditions of
      employees often exposed to cold. The survey was carried out in Portugal and the
      sample consists of 1575 valid responses obtained in 61 industrial units. The
      results show that the food distribution activity sector is characterized by a
      female population (78.1%) and by a young work force (63.4% of the workers are
      less than 35 years old). Despite the availability of cold protective clothing
      (52.8% of the workers indicate one garment) its characteristics require
      improvements. In addition almost 1/3 of the respondents consider the thermal
      environment cold and 79.6% of the workers report that working in the cold is
      harder in wintertime. The results also highlight that 37.3% of the workers report
      having health problems. 

PMID- 23957932
TI  - Pleasant music as a countermeasure against visually induced motion sickness.
AB  - Visually induced motion sickness (VIMS) is a well-known side-effect in virtual
      environments or simulators. However, effective behavioral countermeasures against
      VIMS are still sparse. In this study, we tested whether music can reduce the
      severity of VIMS. Ninety-three volunteers were immersed in an approximately 14
      minute-long video taken during a bicycle ride. Participants were randomly
      assigned to one of four experimental groups, either including relaxing music,
      neutral music, stressful music, or no music. Sickness scores were collected using
      the Fast Motion Sickness Scale and the Simulator Sickness Questionnaire. Results
      showed an overall trend for relaxing music to reduce the severity of VIMS. When
      factoring in the subjective pleasantness of the music, a significant reduction of
      VIMS occurred only when the presented music was perceived as pleasant, regardless
      of the music type. In addition, we found a gender effect with women reporting
      more sickness than men. We assume that the presentation of pleasant music can be
      an effective, low-cost, and easy-to-administer method to reduce VIMS. 

PMID- 23957933
TI  - Effects of thickness, processing technique, and cooling rate protocol on the
      flexural strength of a bilayer ceramic system.
AB  - OBJECTIVE: To determine whether the thickness, processing technique, and cooling
      protocol of veneer ceramic influence the flexural strength of a bilayer ceramic
      system. MATERIALS AND METHODS: Sixty-four bar-shaped specimens (20mm*4mm*1mm) of
      yttria-stabilized tetragonal zirconia (Vita In-Ceram YZ, Vita) were fabricated
      (ISO 6872) and randomly divided into 8 groups (n=8) according to the factors
      "processing technique" (P - PM9 and V - VM9), "thickness" (1mm and 3mm), and
      "cooling protocol" (S - slow and F - fast). The veneer ceramics were applied only
      over one side of the bar-shaped specimens. All specimens were mechanically cycled
      (2*10(6) cycles, 84N, 3.4Hz, in water), with the veneer ceramic under tension.
      Then, the specimens were tested in 4-point bending (1mm/min, load 100kgf, in
      water), also with the veneer ceramic under tension, and the maximum load was
      recorded at first sign of fracture. The flexural strength (sigma) was calculated,
      and the mode of failure was determined by stereomicroscopy (30*). The data (MPa)
      were analyzed statistically by 3-way ANOVA and Tukey's test (alpha=0.05).
      RESULTS: ANOVA revealed that the factor "thickness" (p=0.0001) was statistically
      significant, unlike the factors "processing technique" (p=0.6025) and "cooling
      protocol" (p=0.4199). The predominant mode of failure was cracking. SIGNIFICANCE:
      The thickness of the veneer ceramic has an influence on the mechanical strength
      of the bilayer ceramic system, regardless of processing technique and cooling
      protocol of the veneer ceramic.

PMID- 23957934
TI  - Extrinsic factors promoting insulin producing cell-differentiation and insulin
      expression enhancement-hope for diabetics.
AB  - Diabetes mellitus (DM) is considered to be an autoimmune disorder leading to
      destruction of beta-cells resulting in to a loss of blood sugar control. Attempts
      using many pharmacological compositions including exogenous insulin have failed
      to show tight control of glycemia and associated manifestations. Stem cells are
      considered a potential tool for the supply of insulin-producing cells (IPC)
      generation in vitro. Stem cell differentiation in to pancreatic lineages requires
      influence of both intrinsic and extrinsic factors. Application of islet growth
      factors is considered to be potential for enhancement of beta-cell replication,
      function and survival. Use of certain extrinsic factors is known to facilitate
      expression of transcription factors known to be important for beta-cell
      differentiation and production of insulin enabling IPC generation. Hierarchies of
      secreted signals and transcription factors have been identified by studies from
      several laboratories that guide cell differentiation in to IPC. This knowledge
      provides insights for in vitro IPC differentiation from stem cells. Current
      advancement in medical knowledge promises an insulin independency for DM
      patients. The review sheds light on few specific extrinsic factors which
      facilitate differentiation of stem cells in to IPC in vitro have been discussed;
      which can be proven as a potential therapeutic option for treatment of DM and
      associated diseases. 

PMID- 23957935
TI  - Adipose-derived stem cells and platelet-rich plasma: the keys to functional
      periodontal tissue engineering.
AB  - Numerous different types of periodontal tissue regeneration therapies have been
      developed clinically with variable outcomes and serious limitations. A key goal
      of periodontal therapy is to regenerate the destroyed periodontal tissues
      including alveolar bone, cementum and periodontal ligament. The critical factors
      in attaining successful periodontal tissue regeneration are the correct
      recruitment of cells to the site and the production of a suitable extra cellular
      matrix consistent with the periodontal tissues. Adipose tissue, from which
      mesenchymal stem cells can be harvested easily and safely, is an especially
      attractive stem cell source, because adipose-derived stem cells have a strong
      potential for cell differentiation and growth factor secretion. Meanwhile, the
      usefulness of platelet-rich plasma in the field of dental surgery has attracted
      attention. Therapeutic effects of platelet-rich plasma are believed to occur
      through the provision of concentrated levels of platelet-derived growth factors.
      Further, recent reports suggested the effect of platelet-rich plasma on
      mesenchymal stem cell proliferation, differentiation and survival rate.
      Therefore, the admixture of mesenchymal stem cells and platelet-rich plasma may
      indicate the great potential for tissue regenerations including periodontal
      tissue regeneration. In this review, the potential of adipose-derived stem cells
      and platelet-rich plasma is introduced. Of particular interest, the usefulness in
      periodontal tissue regeneration and future perspective is discussed. 

PMID- 23957936
TI  - gamma-Secretase-regulated signaling typified by Notch signaling in the immune
      system.
AB  - Notch signaling mediates the fates of numerous cells not only in the nervous
      system but also in the immune system. Notch signaling contributes to the
      generation and maintenance of hematopoietic stem cells, lymphocyte development,
      and several immune responses. The molecular mechanism of Notch signaling is
      unique: ligands bind to the extracellular domain of Notch and trigger sequential
      proteolytic cleavages. Finally, gamma-secretase releases the intracellular domain
      (ICD) of Notch (NICD) from the cell membrane, and NICD translocates to the
      nucleus. In the nucleus, NICD binds to transcription factors and modifies the
      expression of certain genes. Thus,gamma-secretase controls Notch signaling.
      Recently, many type 1 transmembrane proteins have been reported to be substrates
      for gamma-secretase, and their ICDs are released from the cell membrane to the
      cytoplasm. It has also been reported that ICDs of several of these substrates
      also translocate to the nucleus. These phenomena closely resemble that of Notch
      signaling. Therefore, the common enzyme -secretase controls the proteolysis and
      turnover of possible signaling molecules, which has led to the hypothesis that
      mechanisms similar to Notch signaling contribute widely to gamma-secretase
      regulated signaling pathways. Indeed, we have shown that the ICD of amyloid
      precursor protein (APP) alters gene expression and induces neuron-specific
      apoptosis. These observations suggest the existence of APP signaling that is
      controlled by gamma-secretase. It is also likely that gamma-secretase-regulated
      signaling pathways, besides Notch signaling, play an essential role in the immune
      system. In fact, CD44, which is involved in hematopoiesis and lymphocyte homing,
      seems to have a gamma-secretase-regulated signaling mechanism. In this review, we
      focus not only on Notch signaling but also on other gamma-secretase-regulated
      signaling pathways in the immune system. 

PMID- 23957938
TI  - Semi-automated scoring of pulmonary emphysema from X-ray CT: trainee
      reproducibility and accuracy.
AB  - OBJECTIVE: We developed a semi-automated tool to quantify emphysema from thoracic
      X-ray multi-detector (64-slice) computed tomography (CT) for training purposes
      and multi-reader studies. MATERIALS AND METHODS: Thoracic X-ray CT was acquired
      in 93 ex-smokers, who were evaluated by six trainees with little or no expertise
      (trainees) and a single experienced thoracic radiologist (expert). A graphic user
      interface (GUI) was developed for emphysema quantification based on the
      percentile of lung where a score of 0=no abnormalities, 1=1-25%, 2=26-50%, 3=51
      75% and 4=76-100% for each lung side/slice. Trainees blinded to subject
      characteristics scored randomized images twice; accuracy was determined by
      comparison to expert scores, density histogram 15th percentile (HU 15), relative
      area at -950 HU (RA(950)), low attenuation clusters at -950 HU (LAC(950)), -856
      HU (LAC(856)) and the diffusing capacity for carbon monoxide (DL(CO%pred)). Intra
      and inter-observer reproducibility was evaluated using coefficients-of-variation
      (COV), intra-class (ICC) and Pearson correlations. RESULTS: Trainee-expert
      correlations were significant (r=0.85-0.97, p<0.0001) and a significant trainee
      bias (0.15 +/- 0.22) was observed. Emphysema score was correlated with RA(950)
      (r=0.88, p<0.0001), HU 15 (r=-0.77, p<0.0001), LAC(950) (r=0.76, p<0.0001),
      LAC(856) (r=0.74, p=0.0001) and DLCO%pred (r=-0.71, p<0.0001). Intra-observer
      reproducibility (COV=4-27%; ICC=0.75-0.94) was moderate to high for trainees;
      intra- and inter-observer COV were negatively and non-linearly correlated with
      emphysema score. CONCLUSION: We developed a GUI for rapid and interactive
      emphysema scoring that allows for comparison of multiple readers with clinical
      and radiological standards.

PMID- 23957939
TI  - T2-weighted MR imaging of the liver: qualitative and quantitative comparison of
      SPACE MR imaging with turbo spin-echo MR imaging.
AB  - OBJECTIVE: To qualitatively and quantitatively compare T2-weighted MR imaging of
      the liver using volumetric spin-echo with sampling perfection with application
      optimized contrast using different flip angle evolutions (SPACE) with
      conventional turbo spin-echo (TSE) sequence for fat-suppressed T2-weighted MR
      imaging of the liver. MATERIALS AND METHODS: Thirty-three patients with suspected
      focal liver lesions had SPACE MR imaging and conventional fat-suppressed TSE MR
      imaging. Images were analyzed quantitatively by measuring the lesion-to-liver
      contrast-to-noise ratio (CNR), and the signal-to-noise ratio (SNR) of main focal
      hepatic lesions, hepatic and splenic parenchyma and qualitatively by evaluating
      the presence of vascular, respiratory motion and cardiac artifacts. Wilcoxon
      signed rank test was used to search for differences between the two sequences.
      RESULTS: SPACE MR imaging showed significantly greater CNR for focal liver
      lesions (median=22.82) than TSE MR imaging (median=14.15) (P<.001). No
      differences were found for SNR of hepatic parenchyma (P=.097), main focal hepatic
      lesions (P=.35), and splenic parenchyma (P=.25). SPACE sequence showed less
      artifacts than TSE sequence (vascular, P<.001; respiratory motion, P<.001;
      cardiac, P<.001) but needed a longer acquisition time (228.4 vs. 162.1s; P<.001).
      CONCLUSION: SPACE MR imaging provides a significantly increased CNR for focal
      liver lesions and less artifacts by comparison with the conventional TSE
      sequence. These results should stimulate further clinical studies with a surgical
      standard of reference to compare the two techniques in terms of sensitivity for
      malignant lesions.

PMID- 23957940
TI  - The anti-shigellosis activity of the methanol extract of Picralima nitida on
      Shigella dysenteriae type I induced diarrhoea in rats.
AB  - BACKGROUND: Picralima nitida Stapf (Apocynaceae) is a medicinal plant used
      traditionally in Cameroon to cure various ailments such as gastrointestinal
      disorders and dysentery. This study reports the in vitro and in vivo anti
      shigellosis activity of the methanol extract of this plant on rats. METHODS: The
      antimicrobial activity of the extract against pathogenic strains was evaluated
      using the disc diffusion assay and broth microdilution method. After oral
      administration of a suspension of Shigella dysenteriae type I (sd1), diarrheic
      rats were divided into 5 groups; the control group received the vehicle of the
      extract and the four others 125, 250, 500 mg/kg of the plant extract and
      ciprofloxacin (20 mg/kg) respectively for 7 days. The frequency of faeces
      emission as well as the weight of normal and diarrheic faeces was recorded. The
      presence of stools containing mucus or blood and the number of sd1 in faeces were
      also recorded. RESULTS: In vitro, the extract had an antimicrobial effect on 11
      out of the 17 pathogenic strains tested. The values of CMI and CMB obtain against
      Shigella dysenteriae type I were 800 and 6400 MUg/ml respectively. In vivo,
      diarrhoea induction was effective and we notice an increase in faeces frequency
      and weight (p < 0.05), increase in the percentage of diarrheic stool released as
      well as the mucus contained in stool (p < 0.05), an increase in bacterial
      population in stool (p < 0.05). Picralima nitida extract, like ciprofloxacin
      markedly reduces the frequency faeces released and sd1 density from 100%
      (diarrheic rats) to 47.22 and 61.69% (500 mg/kg) respectively. It also slowed
      down the movement of charcoal meal through gastro-intestinal tract with the
      percentage of intestinal length covered of 60.54 (500 mg/kg). CONCLUSION: This
      anti-shigellosis activity in vitro and in vivo attests the usefulness of
      Picralima nitida in the traditional treatment of gastrointestinal disorders such
      as dysentery.

PMID- 23957937
TI  - Targeting CSCs in tumor microenvironment: the potential role of ROS-associated
      miRNAs in tumor aggressiveness.
AB  - Reactive oxygen species (ROS) have been widely considered as critical cellular
      signaling molecules involving in various biological processes such as cell
      growth, differentiation, proliferation, apoptosis, and angiogenesis. The
      homeostasis of ROS is critical to maintain normal biological processes. Increased
      production of ROS, namely oxidative stress, due to either endogenous or exogenous
      sources causes irreversible damage of bio-molecules such as DNA, proteins,
      lipids, and sugars, leading to genomic instability, genetic mutation, and altered
      gene expression, eventually contributing to tumorigenesis. A great amount of
      experimental studies in vitro and in vivo have produced solid evidence supporting
      that oxidative stress is strongly associated with increased tumor cell growth,
      treatment resistance, and metastasis, and all of which contribute to tumor
      aggressiveness. More recently, the data have indicated that altered production of
      ROS is also associated with cancer stem cells (CSCs), epithelial-to-mesenchymal
      transition (EMT), and hypoxia, the most common features or phenomena in
      tumorigenesis and tumor progression. However, the exact mechanism by which ROS is
      involved in the regulation of CSC and EMT characteristics as well as hypoxia-
      and, especially, HIF-mediated pathways is not well known. Emerging evidence
      suggests the role of miRNAs in tumorigenesis and progression of human tumors.
      Recently, the data have indicated that altered productions of ROS are associated
      with deregulated expression of miRNAs, suggesting their potential roles in the
      regulation of ROS production. Therefore, targeting ROS mediated through the
      deregulation of miRNAs by novel approaches or by naturally occurring anti-oxidant
      agents such as genistein could provide a new therapeutic approach for the
      prevention and/or treatment of human malignancies. In this article, we will
      discuss the potential role of miRNAs in the regulation of ROS production during
      tumorigenesis. Finally, we will discuss the role of genistein, as a potent anti
      tumor agent in the regulation of ROS production during tumorigenesis and tumor
      development. 

PMID- 23957941
TI  - Anterior cruciate ligament surgery in the rabbit.
AB  - BACKGROUND: Various methods regarding allograft knee replacements have been
      described. The animal models, which are generally used for this purpose include
      sheep, dogs, goats, and pigs, and accrue significant costs for study protocols.
      The authors herein describe an efficient and cost-effective model to study either
      native or tissue-engineered allografts for anterior cruciate ligament (ACL)
      replacement in a New Zealand rabbit model with the potential for transgenic and
      cell migration studies. METHODS: ACL reconstructions were performed in rabbits
      under general anesthesia. For fresh allograft implantations, two animals were
      operated in parallel. Each right extensor digitorum longus tendon was harvested
      and prepared for implantation. After excision of the ACL, tibial and femoral bone
      tunnels were created to implant each graft in the native ACL position. RESULTS:
      During a 2-year period, the authors have successfully undertaken this surgery in
      61 rabbits and have not noticed any major complications attributed to this
      surgical technique. In addition, the authors have observed fast recovery in the
      animals postoperatively. CONCLUSION: The authors recommend this surgical
      procedure as an excellent model for the study of knee surgery.

PMID- 23957942
TI  - Twelve-hour reanimation of a human heart following donation after circulatory
      death.
AB  - Despite increasing use of donation after cardiac death (DCD) and encouraging
      results for non-cardiac transplants, DCD cardiac transplantation has not been
      widely adopted because, (1) the DCD heart sustains warm ischaemic injury during
      the death process and (2) conventional static cold storage significantly adds to
      the ischaemic injury. We have developed a simple system for perfusion of the DCD
      heart with cold crystalloid solution using gravity-feed that can reduce ischaemic
      injury and potentially render the heart suitable for transplantation. This report
      describes the first application of this technique to a human DCD heart with good
      functional metabolic recovery over 12h on an ex vivo rig. 

PMID- 23957943
TI  - Gastric and duodenal squamous cell carcinoma: metastatic or primary?
AB  - Either metastatic or primary squamous cell carcinoma in the gastrointestinal
      tract is extremely rare, with very few cases reported in the literature. In this
      paper, we report a case in which the patient presented with dysphagia during the
      course of radiotherapy for recurrent lung cancer in a mediastinal lymph node.
      Although the dysphagia mimicked radiation esophagitis, the ultimate cause proved
      to be gastric and duodenal metastases from primary lung squamous cell carcinoma.
      Taking into account the value of identification of metastatic or primary SCC in
      the stomach and duodenum on the prognosis and treatment options, it is imperative
      that the correct diagnosis be established. This report is followed by a
      discussion of the differential diagnosis between metastatic and primary squamous
      cell carcinoma in the stomach and duodenum.

PMID- 23957944
TI  - Western-type diet modulates inflammatory responses and impairs functional outcome
      following permanent middle cerebral artery occlusion in aged mice expressing the
      human apolipoprotein E4 allele.
AB  - BACKGROUND: Numerous clinical trials in stroke have failed, most probably
      partially due to preclinical studies using young, healthy male rodents with
      little relevance to the heterogenic conditions of human stroke. Co-morbid
      conditions such as atherosclerosis and infections coupled with advanced age are
      known to contribute to increased risk of cerebrovascular diseases. Clinical and
      preclinical studies have shown that the E4 allele of human apolipoprotein (ApoE4)
      is linked to poorer outcome in various conditions of brain injury and
      neurodegeneration, including cerebral ischemia. Since ApoE is a known regulator
      of lipid homeostasis, we studied the impact of a high-cholesterol diet in aged
      mice in the context of relevant human ApoE isoforms on the outcome of focal brain
      ischemia. METHODS: Aged mice expressing human E3 and E4 isoforms of ApoE in
      C57BL/6J background and C57BL/6J mice fed on either a high-fat diet or a normal
      diet underwent permanent middle cerebral artery occlusion. The impact of a high
      cholesterol diet was assessed by measuring the serum cholesterol level and the
      infarction volume was determined by magnetic resonance imaging. Sensorimotor
      deficits were assessed using an adhesive removal test and the findings were
      correlated with inflammatory markers. RESULTS: We show that expression of human
      ApoE4 renders aged mice fed with a western-type diet more susceptible to
      sensorimotor deficits upon stroke. These deficits are not associated with
      atherosclerosis but are accompanied with altered astroglial activation,
      neurogenesis, cyclooxygenase-2 immunoreactivity and increased plasma IL-6.
      CONCLUSIONS: Our results support the hypothesis that ApoE alleles modify the
      inflammatory responses in the brain and the periphery, thus contributing to
      altered functional outcome following stroke.

PMID- 23957945
TI  - Initial biopsy Gleason score as a predictive marker for survival benefit in
      patients with castration-resistant prostate cancer treated with docetaxel: data
      from the TAX327 study.
AB  - BACKGROUND: Since 2004, docetaxel has been the standard first-line systemic
      therapy for patients with metastatic castration-resistant prostate cancer
      (mCRPC). With abiraterone recently becoming available in the predocetaxel
      setting, it is warranted to identify subgroups of patients who may obtain the
      greatest benefit from docetaxel and particularly qualify for receiving docetaxel
      as first-line treatment for mCRPC. OBJECTIVE: We aimed to identify factors that
      could characterize subgroups of patients who obtain the greatest benefit from the
      use of docetaxel. DESIGN, SETTING, AND PARTICIPANTS: TAX327 was multinational,
      randomized, phase 3 study that was conducted from 2000 to 2002 in 1006 men with
      mCRPC. INTERVENTION: Patients were randomized to receive docetaxel every 3 wk
      (D3), weekly docetaxel (D1), or mitoxantrone every 3 wk (M3), each with
      prednisone. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We investigated
      whether patients with poorly differentiated tumors (Gleason score >=7) at
      diagnosis had greater benefit from D3 compared with M3 than patients with better
      differentiated tumors (Gleason score <=6). Using a Cox model, we compared overall
      survival (OS) between the treatment groups within each subgroup of Gleason score.
      RESULTS AND LIMITATIONS: The TAX 327 data showed that the OS benefit of D3 versus
      M3 was greater in patients with high-grade tumors (median OS: 18.9 vs 14.5 mo;
      p=0.009) than in patients with low-grade tumors (median OS: 21.6 vs 20.7 mo;
      p=0.674). Limitations of a retrospective analysis apply. CONCLUSIONS: The
      survival benefit obtained with docetaxel is most pronounced in patients with high
      Gleason-score tumors (Gleason >=7). In a time of shifting paradigms in mCRPC,
      with abiraterone becoming available prior to docetaxel chemotherapy, Gleason
      score may help in selecting patients who obtain the greatest benefit from
      docetaxel as first-line treatment for mCRPC. Prospective validation of these
      findings is warranted.

PMID- 23957946
TI  - Long-term continence outcomes in men undergoing radical prostatectomy for
      clinically localized prostate cancer.
AB  - BACKGROUND: Urinary incontinence is a common short-term complication of radical
      prostatectomy (RP). Little is known about the long-term impact of RP on
      continence. OBJECTIVE: To elucidate the long-term progression of continence after
      RP. DESIGN, SETTING, AND PARTICIPANTS: From October 2000 through September 2012,
      1788 men undergoing open RP for clinically localized prostate cancer by a single
      surgeon at an urban tertiary care center prospectively signed consent to be
      followed before RP and at 3, 6, 12, 24, 96, and 120 mo after RP. A consecutive
      sampling method was used and all men were included in this study. INTERVENTION:
      Men underwent open RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Regression
      models controlled for preoperative University of California, Los Angeles-Prostate
      Cancer Index urinary function score (UCLA-PCI-UFS), age, prostate-specific
      antigen level, Gleason score, stage, nerve-sparing status, race, and marital
      status were used to evaluate the association of time since RP with two dependent
      variables: UCLA-PCI-UFS and continence status. RESULTS AND LIMITATION: The mean
      UCLA-PCI-UFS declined between 2 yr and 8 yr (83.8 vs 81.8; p=0.007) and
      marginally between 8 yr and 10 yr (81.8 vs 79.6; p=0.036) after RP, whereas
      continence rate did not significantly change during these intervals. Men >= 60 yr
      old experienced a decline in mean UCLA-PCI-UFS between 2 yr and 8 yr (p=0.002)
      and a marginal decline in continence rate between 2 yr and 10 yr (p=0.047),
      whereas these variables did not change significantly in men <60 yr old. These
      outcomes are for an experienced surgeon, so caution should be exercised in
      generalizing these results. CONCLUSIONS: Between 2 yr and 10 yr after RP, there
      were slight decreases in mean UCLA-PCI-UFS and continence rates in this study.
      Men aged <60 yr had better long-term outcomes. These results provide realistic
      long-term continence expectations for men undergoing RP.

PMID- 23957947
TI  - Current perspectives in the use of molecular imaging to target surgical
      treatments for genitourinary cancers.
AB  - CONTEXT: Molecular imaging (MI) entails the visualisation, characterisation, and
      measurement of biologic processes at the molecular and cellular levels in humans
      and other living systems. Translating this technology to interventions in real
      time enables interventional MI/image-guided surgery, for example, by providing
      better detection of tumours and their dimensions. OBJECTIVE: To summarise and
      critically analyse the available evidence on image-guided surgery for
      genitourinary (GU) oncologic diseases. EVIDENCE ACQUISITION: A comprehensive
      literature review was performed using PubMed and the Thomson Reuters Web of
      Science. In the free-text protocol, the following terms were applied: molecular
      imaging, genitourinary oncologic surgery, surgical navigation, image-guided
      surgery, and augmented reality. Review articles, editorials, commentaries, and
      letters to the editor were included if deemed to contain relevant information. We
      selected 79 articles according to the search strategy based on the Preferred
      Reporting Items for Systematic Reviews and Meta-analysis criteria and the IDEAL
      method. EVIDENCE SYNTHESIS: MI techniques included optical imaging and
      fluorescent techniques, the augmented reality (AR) navigation system, magnetic
      resonance imaging spectroscopy, positron emission tomography, and single-photon
      emission computed tomography. Experimental studies on the AR navigation system
      were restricted to the detection and therapy of adrenal and renal malignancies
      and in the relatively infrequent cases of prostate cancer, whereas fluorescence
      techniques and optical imaging presented a wide application of intraoperative GU
      oncologic surgery. In most cases, image-guided surgery was shown to improve the
      surgical resectability of tumours. CONCLUSIONS: Based on the evidence to date,
      image-guided surgery has promise in the near future for multiple GU malignancies.
      Further optimisation of targeted imaging agents, along with the integration of
      imaging modalities, is necessary to further enhance intraoperative GU oncologic
      surgery.

PMID- 23957948
TI  - Castration-resistant prostate cancer: from new pathophysiology to new treatment.
AB  - CONTEXT: Until recently, the only approved agent for metastatic castration
      resistant prostate cancer (mCRPC) was docetaxel chemotherapy. But over the last 5
      years, significant advances in the field have led to the approval of five new
      agents, each with different mechanisms of action and demonstrating improved
      overall survival in separate randomized phase 3 trials. Many of these novel
      agents are now also being evaluated in earlier stages of the disease, which may
      ultimately lead to even better outcomes. OBJECTIVE: To summarize the current
      literature on the management of mCRPC with a particular focus on novel
      chemotherapy approaches, hormonal approaches, immunotherapy, and
      radiopharmaceuticals showing survival benefits in phase 3 clinical trials.
      Emerging therapies in late stages of development are also discussed briefly.
      EVIDENCE ACQUISITION: A comprehensive search of PubMed, identified studies
      pertaining to novel therapies evaluated in mCRPC since the initial approval of
      docetaxel in 2004. Abstracts from major international meetings were hand searched
      to identify studies of novel agents in late stage development in mCRPC. The
      Clinical Trials.gov database was used to find ongoing clinical trials in the area
      of mCRPC. A detailed search of each new agent was also performed to ensure that
      additional trials of these agents in other stages of the disease were included
      where relevant. EVIDENCE SYNTHESIS: The main agents discussed are the androgen
      synthesis inhibitor abiraterone acetate, the androgen receptor inhibitor
      enzalutamide, the novel taxane chemotherapy cabazitaxel, the immunotherapy
      sipuleucel-T, and the radiopharmaceutical radium 223. Other emerging agents and a
      brief discussion of negative phase 3 results are also included. CONCLUSIONS: It
      is a very exciting time in the field of mCRPC, where therapeutic advances have
      improved outcomes in this disease, although once metastatic overall median
      survival remains a dismal 2-3 years. The key now will be to understand how best
      to use these new agents, understand the mechanisms of resistance to them,
      continue to develop novel treatment strategies, and ultimately test these agents
      earlier in the disease when cure may be possible.

PMID- 23957950
TI  - Drug metabolite generation using a laboratory evolved NADPH independent
      cytochrome P450: application of in vitro and in silico approaches.
AB  - Twelve disparate drugs were subjected to metabolite generation by a laboratory
      evolved bacterial cytochrome P450 to investigate feasibility of the bacterial CYP
      to generate drug metabolites. Seven drugs were metabolised by the bacterial
      cytochromes to give diverse metabolites, which were compared to human metabolites
      reported in literature. Several non human metabolites were also generated by the
      bacterial CYP in addition to the known human metabolites. From docking studies
      and in silico sites of metabolism results, it was shown that the binding mode of
      the drug molecule and its distance from the active site in the binding pocket of
      the CYP was important for metabolism. This contribution reports, for the first
      time, previously uncharacterised metabolites of this bacterial cytochrome and
      demonstrates the potential usefulness of human CYP-based prediction software when
      used in combination with bacterial CYPs for metabolite generation. 

PMID- 23957951
TI  - Pharmacokinetics of hydroxymethylnitrofurazone and its parent drug nitrofurazone
      in rabbits.
AB  - The prodrug hydroximethylnitrofurazone (NFOH) presents antichagasic activity with
      greatly reduced toxicity compared to its drug matrix nitrofurazone (NF). Besides
      these new characteristics, the prodrug was more active against the parasite T.
      cruzi amastigotes. These advantages make the prodrug a possible therapeutic
      alternative for the treatment of both acute and the chronic phase of Chagas
      disease. However, the knowledge of pharmacokinetic profile is crucial to evaluate
      the feasibility of a new drug. In this study, our objective was to evaluate the
      in vivo formation of NF from the NFOH single administration and to evaluate its
      pharmacokinetic profile and compared it to NF administration. A bioanalytical
      method to determine the NF and NFOH by LCMS/MS was developed and validated to
      perform these investigations. Male albino rabbits (n=15) received NF
      intravenously and orally in doses of 6.35 and 63.5 mg / kg respectively, and
      NFOH, 80.5 mg / kg orally. The serial blood samples were processed and analyzed
      by mass spectrometry. The system operated in positive and negative modes for the
      analites determination, under elution of the mobile phase 50:50 water: methanol.
      The administration of NFOH allowed the calculation of pharmacokinetic parameters
      for the prodrug, and the NF obtained from NFOH administration. Using the
      pharmacokinetic profile obtained from the NF i.v. administration, the oral
      bioavailability of NF from the administered prodrug was obtained (60.1%) and, as
      a key parameter in a prodrug administration, should be considered in future
      studies. The i.v. and oral administrations of NF differ in the constant of
      elimination (0.04 vs 0.002) and elimination half-life (17.32 min vs 276.09 min)
      due to the low solubility of the drug that hinders the formation of molecular
      dispersions in the digestory tract. Still, there was observed no statistical
      differences were observed between the pharmacokinetic parameters of orally
      administered NF and NF obtained from NFOH. The calculated area under the curve
      (AUC 0-infinity) showed that the exposure to the parental drug was fairly the
      same (844.79 vs 566.44) for NF and NF obtained from the prodrug administration.
      The tendency to higher NF's mean residence time (MRT) as observed in the prodrug
      administration (956.1 min vs 496.3 min) guarantees longer time for the action of
      the drug and it allows the expansion of the administration intervals. These
      findings, added with the beneficial characteristics of the prodrug encourage new
      efficacy tests towards the clinical use of NFOH. 

PMID- 23957952
TI  - Cushing syndrome and giant sterile abscess induced by self intramuscular
      injection of supra-therapeutic doses of triamcinolone.
AB  - OBJECTIVE: Corticosteroid are among the most commonly used medications for a wide
      range of inflammatory, autoimmune and neoplastic disorders. Therefore, it is
      important for the physician to be aware of their side effects, in relation to
      different forms and delivery, that occur more often with oral therapy. METHODS: A
      33-year old professional drummer had been suffering from bilateral tenosynovitis
      of the wrists for three months. In order to accelerate the recovery and play
      drums again, he self-injected supra-therapeutic doses of triamcinolone acetonide
      (a total of injected drug > 2,400 mg was calculated) in his right gluteus.
      RESULTS: The intramuscular overuse of triamcinolone acetonide caused Cushing
      syndrome associated with a giant sterile abscess that involved the right gluteal
      muscles and the adjacent subcutaneous tissue. CONCLUSION: A large intramuscular
      sterile abscess can be a side effect of supra-therapeutic intramuscular
      triamcinolone dose and this should be explained to the patient prior to
      initiation of treatment with triamcinolone.

PMID- 23957953
TI  - A mutation in the serine protease TMPRSS4 in a novel pediatric neurodegenerative
      disorder.
AB  - BACKGROUND: To elucidate the genetic basis of a novel neurodegenerative disorder
      in an Old Order Amish pedigree by combining homozygosity mapping with exome
      sequencing. METHODS AND RESULTS: We identified four individuals with an autosomal
      recessive condition affecting the central nervous system (CNS). Neuroimaging
      studies identified progressive global CNS tissue loss presenting early in life,
      associated with microcephaly, seizures, and psychomotor retardation; based on
      this, we named the condition Autosomal Recessive Cerebral Atrophy (ARCA). Using
      two unbiased genetic approaches, homozygosity mapping and exome sequencing, we
      narrowed the candidate region to chromosome 11q and identified the c.995C > T
      (p.Thr332Met) mutation in the TMPRSS4 gene. Sanger sequencing of additional
      relatives confirmed that the c.995C > T genotype segregates with the ARCA
      phenotype. Residue Thr332 is conserved across species and among various ethnic
      groups. The mutation is predicted to be deleterious, most likely due to a protein
      structure alteration as demonstrated with protein modelling. CONCLUSIONS: This
      novel disease is the first to demonstrate a neurological role for a transmembrane
      serine proteases family member. This study demonstrates a proof-of-concept
      whereby combining exome sequencing with homozygosity mapping can find the genetic
      cause of a rare disease and acquire better understanding of a poorly described
      protein in human development.

PMID- 23957954
TI  - Combined large cell neuroendocrine carcinoma with giant cell carcinoma of the
      lungs: a case report.
AB  - Combined large cell neuroendocrine carcinoma of the lungs (combined LCNEC) with
      giant cell carcinoma is extremely rare. A 65-year-old man was found to have an
      abnormal shadow in his left lung field. Computed tomography revealed a solid,
      round mass measuring 2.8 * 2.2 cm that was located in the left S9. The patient
      underwent left lower lobectomy and mediastinal lymph node dissection.
      Histopathological examination revealed an LCNEC, combined with giant cell
      carcinoma. The patient received by S-1 (TS-1, an oral fluoropyrimidine)
      chemotherapy, and he has been disease-free for over 8 months. Combined LCNEC with
      giant cell carcinoma is an extremely rare tumor with high malignant potential,
      and thus, multidisciplinary therapy and close follow-up are advised.

PMID- 23957955
TI  - Moringa Oleifera aqueous leaf extract down-regulates nuclear factor-kappaB and
      increases cytotoxic effect of chemotherapy in pancreatic cancer cells.
AB  - BACKGROUND: Fewer than 6% patients with adenocarcinoma of the pancreas live up to
      five years after diagnosis. Chemotherapy is currently the standard treatment,
      however, these tumors often develop drug resistance over time. Agents for
      increasing the cytotoxic effects of chemotherapy or reducing the cancer cells'
      chemo-resistance to the drugs are required to improve treatment outcome. Nuclear
      factor kappa B (NF-kB), a pro-inflammatory transcription factor, reportedly plays
      a significant role in the resistance of pancreatic cancer cells to apoptosis
      based chemotherapy. This study investigated the effect of aqueous Moringa
      Oleifera leaf extract on cultured human pancreatic cancer cells - Panc-1, p34,
      and COLO 357, and whether it can potentiates the effect of cisplatin chemotherapy
      on these cells. METHODS: The effect of Moringa Oleifera leaf extract alone and in
      combination with cisplatin on the survival of cultured human pancreatic cancer
      cells was evaluated by XTT-based colorimetric assay. The distribution of Panc-1
      cells in the cell cycle following treatment with Moringa leaf extract was
      evaluated by flow cytometry, and evaluations of protein levels were via
      immunoblotting. Data of cell survival following combined treatments were analyzed
      with Calcusyn software. RESULTS: Moringa Oleifera leaf extract inhibited the
      growth of all pancreatic cell lines tested. This effect was significant in all
      cells following exposure to >=0.75 mg/ml of the extract. Exposure of Panc-1 cells
      to Moringa leaf extract induced an elevation in the sub-G1 cell population of the
      cell-cycle, and reduced the expression of p65, p-IkBalpha and IkBalpha proteins
      in crude cell extracts. Lastly, Moringa Oleifera leaf extract synergistically
      enhanced the cytotoxic effect of cisplatin on Panc-1 cells. CONCLUSION: Moringa
      Oleifera leaf extract inhibits the growth of pancreatic cancer cells, the cells
      NF-kappaB signaling pathway, and increases the efficacy of chemotherapy in human
      pancreatic cancer cells.

PMID- 23957958
TI  - Loneliness trajectories.
AB  - This special section brings together five studies using group-based modeling to
      capture developmental trajectories of loneliness from age 7 through age 20.
      Together, the findings from these studies provide further evidence that
      developmental trajectories of loneliness are likely not best understood at a
      continuum but reflect distinct subpopulations that differ both where they start
      out and how they change over time in terms of mean levels of loneliness.
      Furthermore, adolescents who show chronically high loneliness or increasing
      loneliness over time exhibit poorer psychological and physical health, including
      greater incidence of depressive symptoms and more frequent suicide attempts. The
      findings from these studies also suggest that individuals experiencing increases
      in loneliness with age fare worse as well in terms of both physical and
      psychological health. 

PMID- 23957956
TI  - Killer Immunoglobulin-like Receptors (KIR) haplogroups A and B track with Natural
      Killer Cells and Cytokine Profile in Aged Subjects: Observations from
      Octo/Nonagenarians in the Belfast Elderly Longitudinal Free-living Aging STudy
      (BELFAST).
AB  - BACKGROUND: Natural Killer Cells (NK) play an important role in detection and
      elimination of virus-infected, damaged or cancer cells. NK cell function is
      guided by expression of Killer Immunoglobulin-like Receptors (KIRs) and
      contributed to by the cytokine milieu. KIR molecules are grouped on NK cells into
      stimulatory and inhibitory KIR haplotypes A and B, through which NKs sense and
      tolerate HLA self-antigens or up-regulate the NK-cytotoxic response to cells with
      altered HLA self-antigens, damaged by viruses or tumours. We have previously
      described increased numbers of NK and NK-related subsets in association with sIL
      2R cytokine serum levels in BELFAST octo/nonagenarians. We hypothesised that
      changes in KIR A and B haplotype gene frequencies could explain the increased
      cytokine profiles and NK compartments previously described in Belfast Elderly
      Longitudinal Free-living Aging STudy (BELFAST) octo/nonagenarians, who show
      evidence of ageing well. RESULTS: In the BELFAST study, 24% of octo/nonagenarians
      carried the KIR A haplotype and 76% KIR B haplotype with no differences for KIR A
      haplogroup frequency between male or female subjects (23% v 24%; p=0.88) or for
      KIR B haplogroup (77% v 76%; p=0.99). Octo/nonagenarian KIR A haplotype carriers
      showed increased NK numbers and percentage compared to Group B KIR subjects
      (p=0.003; p=0.016 respectively). There were no KIR A/ B haplogroup-associated
      changes for related CD57+CD8 (high or low) subsets. Using logistic regression,
      KIR B carriers were predicted to have higher IL-12 cytokine levels compared to
      KIR A carriers by about 3% (OR 1.03, confidence limits CI 0.99-1.09; p=0.027) and
      14% higher levels for TGF-beta (active), a cytokine with an anti-inflammatory
      role, (OR 1.14, confidence limits CI 0.99-1.09; p=0.002). CONCLUSION: In this
      observational study, BELFAST octo/nonagenarians carrying KIR A haplotype showed
      higher NK cell numbers and percentage compared to KIR B carriers. Conversely, KIR
      B haplotype carriers, with genes encoding for activating KIRs, showed a tendency
      for higher serum pro-inflammatory cytokines compared to KIR A carriers. While the
      findings in this study should be considered exploratory they may serve to
      stimulate debate about the immune signatures of those who appear to age slowly
      and who represent a model for good quality survivor-hood.

PMID- 23957960
TI  - Impaired specific CD8 T cell response with aging is not due to decreased
      expression of CD90 on TCR transgenic T cells.
AB  - BACKGROUND: CD90 (Thy-1) is a small glycoprotein that is particularly abundant on
      the surface of mouse thymocytes and peripheral T cells, and is often used as a
      marker in adoptive transfer experiments to distinguish donor and recipient T
      cells with different CD90 subtypes. We have performed adoptive transfer
      experiments with T cell receptor transgenic (TCR Tg) mice to study the impaired
      CD8 T cell response with aging. FINDINGS: After stimulation with a CD8 T cell
      epitope, HA518-524, the response of TCR Tg CD8 T cells from aged mice was
      decreased compared to the response of TCR Tg T cells from young mice. CD90
      expression was also substantially decreased on the TCR Tg CD8 T cells of aged
      mice. However, the responses of CD90hi and CD90low CD8 T cells of the aged mice
      were similar in both early activation and proliferation, demonstrating that the
      impaired Tg T cell response with aging is not associated with the altered CD90
      expression on CD8 T cells. CONCLUSIONS: The impaired Tg CD8 T cell response in
      aged mice is not due to age-associated changes in CD90 expression on Tg CD8 T
      cells.

PMID- 23957959
TI  - Phylogenetic diversity of Flavobacteria isolated from the North Sea on solid
      media.
AB  - Flavobacteria are abundant in the North Sea, an epeiric sea on the continental
      shelf of Europe. However, this abundance has so far not been reflected by the
      number of strains in culture collections. In this study, Flavobacteria were
      isolated from pelagic and benthic samples, such as seawater, phytoplankton,
      sediment and its porewater, and from surfaces of animals and seaweeds on agar
      plates with a variety of carbon sources. Dilution cultivation with a new medium,
      incubation at low temperatures and with long incubation times, and colony
      screening by a Flavobacteria-Cytophagia-specific PCR detecting 16S rRNA gene
      sequences led to a collection of phylogenetically diverse strains. Two strains
      affiliated with Flammeovirgaceae and seven strains affiliated with
      Cyclobacteriaceae, whereas within the Flavobacteriaceae 20 isolated strains
      presumably represented seven novel candidate genera and 355 strains affiliated
      with 26 of 80 validly described marine Flavobacteriaceae genera, based on a genus
      boundary of 95.0% 16S rRNA gene sequence identity. The majority of strains (276)
      affiliated with 37 known species in 16 genera (based on a boundary of 98.7% 16S
      rRNA gene sequence identity), whereas 79 strains likely represented 42 novel
      species in 22 established Flavobacteriaceae genera. Pigmentation, iridescence,
      gliding motility, agar lysis, and flexirubin as a chemical marker supported the
      taxonomy at the species level. This study demonstrated the culturability on solid
      medium of phylogenetically diverse Flavobacteria originating from the North Sea. 

PMID- 23957961
TI  - Physiological responses of young thoroughbred horses to intermittent high
      intensity treadmill training.
AB  - BACKGROUND: Training of young Thoroughbred horses must balance development of
      cardiopulmonary function and aerobic capacity with loading of the musculoskeletal
      system that can potentially cause structural damage and/or lameness. High-speed
      equine treadmills are sometimes used to supplement exercise on a track in the
      training of young Thoroughbreds because the horse can run at high speeds but
      without the added weight of a rider. We tested the hypothesis that intermittent
      high-intensity exercise on a treadmill of young Thoroughbred horses entering
      training can enhance development of aerobic capacity (VO2max) and running
      performance more than conventional training under saddle, and do so without
      causing lameness. RESULTS: Twelve yearling Thoroughbreds trained for 8 months
      with conventional riding (C) only, conventional riding plus a short (2 month, S)
      interval of once-per-week high-intensity treadmill exercise, or a long (8 month,
      L) interval of once-per-week high-intensity treadmill exercise. Three treadmill
      exercise tests evaluated VO2max, oxygen transport and running performance
      variables in June of the yearling year (only for L), October of the yearling year
      and April of the 2-year-old year. No horses experienced lameness during the
      study. Aerobic capacity increased in all groups after training. In both October
      and April, VO2max in L was higher than in C, but did not differ between L and S
      or S and C. Running speeds eliciting VO2max also increased in all groups after
      training, with S (809+/-3 m/s) and L (804+/-9 m/s) higher than C (764+/-27 m/s).
      Maximum heart rate decreased for all groups after training. Hematocrit and
      hemoglobin concentration increased for L throughout training. CONCLUSIONS: Young
      Thoroughbred horses can increase aerobic capacity and running performance more
      than by strictly using track training under saddle with the addition of
      intermittent high-intensity treadmill exercise, and they can do so without
      experiencing lameness. This finding suggests that young racehorses might be able
      to achieve higher aerobic fitness during training without subjecting their
      musculoskeletal systems to increased loading and risk of developing lameness. The
      findings of this preliminary study do not indicate a specific protocol to best
      achieve this goal.

PMID- 23957962
TI  - Educational potential of a virtual patient system for caring for traumatized
      patients in primary care.
AB  - BACKGROUND: Virtual Patients (VPs) have been used in undergraduate healthcare
      education for many years. This project is focused on using VPs for training
      professionals to care for highly vulnerable patient populations. The aim of the
      study was to evaluate if Refugee Trauma VPs was perceived as an effective and
      engaging learning tool by primary care professionals (PCPs) in a Primary Health
      Care Centre (PHC). METHODS: A VP system was designed to create realistic and
      engaging VP cases for Refugee Trauma for training refugee patient interview, use
      of established trauma and mental health instruments as well as to give feedback
      to the learners. The patient interview section was based on video clips with a
      Bosnian actor with a trauma story and mental health problems. The video clips
      were recorded in Bosnian language to further increase the realism, but also
      subtitled in English. The system was evaluated by 11 volunteering primary health
      clinicians at the Lynn Community Health Centre, Lynn, Massachusetts, USA. The
      participants were invited to provide insights/feedback about the system's
      usefulness and educational value. A mixed methodological approach was used,
      generating both quantitative and qualitative data. RESULTS: Self-reported
      dimensions of clinical care, pre and post questionnaire questions on the PCPs
      clinical worldview, motivation to use the VP, and IT Proficiency. Construct items
      used in these questionnaires had previously demonstrated high face and construct
      validity. The participants ranked the mental status examination more positively
      after the simulation exercise compared to before the simulation. Follow up
      interviews supported the results. CONCLUSIONS: Even though virtual clinical
      encounters are quite a new paradigm in PHC, the participants in the present study
      considered our VP case to be a relevant and promising educational tool. Next
      phase of our project will be a RCT study including comparison with specially
      prepared paper-cases and determinative input on improving clinical diagnosis and
      treatment of the traumatized refugee patient.

PMID- 23957963
TI  - Impact of the gut microbiome on mucosal inflammation.
AB  - In the past 10 years it has become increasingly apparent that the gut microbiome
      has profound effects on the immune system to which it is juxtaposed, the mucosal
      immune system. Here, I explore recent studies in which the effects of the
      microbiota expand or facilitate anti-inflammatory or regulatory immunological
      machinery or which favor development of proinflammatory immunological machinery
      in this system. I then focus on how these opposing processes play out in
      inflammatory bowel disease (IBD); a disease in which normal immune homeostasis is
      disturbed and inflammation takes hold. 

PMID- 23957964
TI  - 10-year long-term survival (LTS) of induction chemotherapy with three cycles
      cisplatin/paclitaxel followed by concurrent chemoradiation cisplatin/etoposide/45
      Gy (1.5 Gy bid) plus surgery in locally advanced non-small-cell lung cancer
      (NSCLC)-a multicenter phase-II trial (CISTAXOL).
AB  - BACKGROUND: Induction chemoradiotherapy plus surgery remains an option to study
      in IIIA(N2) and selected IIIB NSCLC. Here we report ten-year long-term survival
      of a prospective multicenter German-French phase-II trial with trimodality.
      PATIENTS AND METHODS: Mediastinoscopically proven IIIA(N2)/selected IIIB NSCLC
      received three cycles cisplatin (50 mg/m(2) day 1+8) and paclitaxel (175
      mg/m(2)d1) qd 22. Concurrent CTx/RTx followed: 45 Gy (1.5 Gy bid) with cisplatin
      50 mg/m(2) day 2+9 and etoposide 100 mg/m(2) d 4-6. Surgery was planned three to
      five weeks after RTx. If evaluated inoperable/irresectable at the end of RTx,
      definitive RTx-boost (20 Gy; 2 Gy qd) followed. Here we report 10-year-LTS for
      this cohort. RESULTS: All 64 patients were accrued 3/99 to 2/02. Patients
      characteristics: IIIA(N2)/IIIB 25/39; m/f 48/16; adeno/squamous/large
      cell/adenosquamous/NOS 15/26/18/3/2; age: median 52.5 (range 33-69). 36 operated:
      R0 32/36 (89%); pCR 16/36 (44%). 10-year-LTS%; all 26.0; IIIA(N2) 37.1; IIIB
      17.9; relevant prognostic factors (exploratory): pretreatment - histopathology
      (squamous/adeno) - age (<50/>=50) - Charlson-CI: 1/>1 - BMI (>=25/<25) - pack
      years smoking (>=10/<10); treatment-dependent - R0/no-R0. CONCLUSIONS: This
      regimen achieves substantial LTS. Interestingly, adenocarcinomas, older patients,
      unfavorable comorbidity scores, higher BMI and light smokers demonstrate poor
      long-term outcome even with aggressive trimodality. This dataset defines the
      rationale for our ongoing randomized trial with surgery after induction therapy
      in IIIA(N2)/selected IIIB (ESPATU).

PMID- 23957965
TI  - Kinetic effects of TiO2 fine particles and nanoparticles aggregates on the
      nanomechanical properties of human neutrophils assessed by force spectroscopy.
AB  - BACKGROUND: Increasing applications of titanium dioxide (TiO2) fine particles
      (FPs) and nanoparticles (NPs) require coupled knowledge improvement concerning
      their biokinetic effects. Neutrophils are quickly recruited to titanium
      implantation areas. Neutrophils mechanical properties display a crucial role on
      cell physiology and immune responsive functions. Then, micro and nanomechanical
      characterization assessed by force spectroscopy (FS) technique has been largely
      applied in this field. RESULTS: Scanning electron microscopy (SEM) images
      highlighted neutrophils morphological changes along TiO2 FPs and NPs aggregates
      exposure time (1, 5, and 30 min) compared to controls. FS approaches showed an
      increasing on attraction forces to TiO2 FPs and NPs treated neutrophils. This
      group depicted stronger stiffness features than controls just at 1 min of
      exposure. Treated neutrophils showed a tendency to increase adhesive properties
      after 1 and 5 min of exposure. These cells maintained comparatively higher
      elasticity behavior for a longer time possibly due to intense phagocytosis and
      cell stiffness opposing to the tip indentation. Neutrophils activation caused by
      FPs and NPs uptake could be related to increasing dissipated energy results.
      CONCLUSIONS: Mechanical modifications resulted from TiO2 FPs and NPs aggregates
      interaction with neutrophils showed increasing stiffness and also cell morphology
      alteration. Cells treatment by this metal FPs and NPs caused an increase in
      attractive forces. This event was mainly observed on the initial exposure times
      probably regarding to the interaction of neutrophils membrane and phagocytosis.
      Similar results were found to adhesion forces and dissipated energy outcomes.
      Treated cells presented comparatively higher elasticity behavior for a longer
      time. SEM images clearly suggested cell morphology alteration along time course
      probably related to activation, cytoskeleton rearrangement and phagocytosis. This
      scenario with increase in stiffness strongly suggests a direct relationship over
      neutrophil rolling, arrest, and transmigration. Scrutinizing these interactions
      represents an essential step to clarify the mechanisms involved on treatments
      containing micro and nanomaterials and their fates on the organisms.

PMID- 23957966
TI  - Inflammatory myofibroblastic tumor with extensive involvement of the bladder in
      an adolescent: a case report.
AB  - Inflammatory myofibroblastic tumor (IMT) is a rare lesion of unclear pathogenesis
      that shows a wide, highly variable spectrum of clinical behavior. We describe the
      case of a 17-year-old boy with a large IMT that infiltrated the bladder,
      ileocecal junction, peritoneum and pelvic retroperitoneal space. The tumor was
      associated with extensive toughening and thickening of the bladder, and, although
      it showed a tendency for invasive growth, it affected mainly the bladder and
      adjacent tissue. To the best of our knowledge, this case report is the first to
      describe an IMT involving the entire bladder and several adjacent pelviabdominal
      organs. The bladder wall was tough and could hardly be cut by scalpel. Levels of
      inflammatory response markers such as C-reactive protein fell after surgery. 

PMID- 23957967
TI  - A picture is worth a thousand words: ethical dilemmas presented by storing
      digital photographs in electronic health records.

PMID- 23957968
TI  - Management of autoimmune bullous diseases: pharmacology and therapeutics.

PMID- 23957969
TI  - A look back, a peek forward.

PMID- 23957970
TI  - Acne masquerading as malignant melanoma on positron emission tomography-computed
      tomography scan.

PMID- 23957971
TI  - High sun-protection factor sunscreens (>=70) may provide ultraviolet protection
      above minimal recommended levels by adequately compensating for lower sunscreen
      user application amounts.

PMID- 23957972
TI  - Sun-protection factor confounded by anti-inflammatory activity of sunscreen
      agents?

PMID- 23957973
TI  - What is the significance of anti-inflammatory activity of UV filters in
      sunscreens?

PMID- 23957974
TI  - Summertime elbow eruptions: facts and friction.

PMID- 23957975
TI  - Photoallergic reactions to varenicline mimicking brachioradial pruritus.

PMID- 23957976
TI  - CD4+CD25+FOXP3+ malignant T cells in Sezary syndrome are not necessarily
      functional regulatory T cells.

PMID- 23957977
TI  - Reply to: Summertime elbow eruptions.

PMID- 23957978
TI  - "Arrow" sign: a rapid microscopic diagnosis of hair change associated with
      epidermal growth factor receptor inhibitors.

PMID- 23957979
TI  - Efficacy and safety of calcipotriol/betamethasone dipropionate ointment for the
      treatment of simple onycholysis: an open-label study.

PMID- 23957980
TI  - Improving patient advocacy through smartphones: a needs assessment.

PMID- 23957981
TI  - Treatment of interdigital-type tinea pedis with a 2-week regimen of wearing
      hygienic socks loaded with antifungal microcapsules: a randomized, double-blind,
      placebo-controlled study.

PMID- 23957982
TI  - Methylprednisolone pulse therapy for Stevens-Johnson syndrome/toxic epidermal
      necrolysis: clinical evaluation and analysis of biomarkers.

PMID- 23957983
TI  - Infantile transient smooth muscle contraction of the skin.

PMID- 23957984
TI  - Primary cutaneous B-cell lymphomas: part I. Clinical features, diagnosis, and
      classification.
AB  - Primary cutaneous B-cell lymphomas (PCBCLs) are defined as lymphomas with a B
      cell phenotype that present in the skin without evidence of systemic or
      extracutaneous disease at initial presentation, after adequate staging. In non
      Hodgkin lymphomas, the skin is the second most common site of extranodal
      involvement after the gastrointestinal tract. PCBCLs are histologically very
      similar to their nodal counterparts, and these histologic similarities can lead
      to confusion about both therapy and prognosis. This article will summarize the
      clinical, pathologic, and diagnostic features of the 3 main types of PCBCL:
      primary cutaneous follicle center lymphoma, primary cutaneous marginal zone
      lymphoma, and primary cutaneous diffuse large B-cell lymphoma, leg-type, and the
      appropriate evaluation and staging procedures for each of these entities. 

PMID- 23957985
TI  - Primary cutaneous B-cell lymphomas: part II. Therapy and future directions.
AB  - The choice of therapy for primary cutaneous B-cell lymphoma (PCBCL) relies on
      correct histopathologic classification and the exclusion of systemic disease. In
      part II of this continuing medical education article, we will review the
      available therapies for the different types of PCBCL. Primary cutaneous follicle
      center lymphoma (PCFCL) and primary cutaneous marginal zone lymphoma (PCMZL) are
      indolent tumors with an excellent prognosis. They are managed similarly with
      local therapy, such as radiotherapy or surgical excision, for isolated disease
      and observation for asymptomatic multifocal presentations. Relapses are common in
      both PCFCL and PCMZL, but overall survival remains excellent. Primary cutaneous
      diffuse large B-cell lymphoma (both leg type and other) has a much poorer
      prognosis than indolent PCBCL, and it often requires an aggressive approach with
      radiation therapy and/or multiagent chemotherapy. Investigational approaches hold
      promise for the treatment of these malignancies, particularly primary cutaneous
      diffuse large B-cell lymphoma. 

PMID- 23957988
TI  - Pigmentation in a scar: use of dermoscopy in the management decision.

PMID- 23957989
TI  - Techniques for minimizing pain with injections.

PMID- 23957990
TI  - A simple method for predicting postprocedure pigmentation in Asian patients.

PMID- 23957991
TI  - Long-lasting effect of vascular targeted therapy of melasma.

PMID- 23957992
TI  - Angiosarcoma in patients with xeroderma pigmentosum: less aggressive and not so
      rare?

PMID- 23957993
TI  - Distal acquired benign symmetric lipomatosis: a rare subtype of an uncommon
      entity.

PMID- 23957994
TI  - Late-onset melanopenic hypomelanosis as a complication of cosmetic eyeliner
      tattoo.

PMID- 23957995
TI  - Intradermal sodium thiosulfate for exophytic calcinosis cutis of connective
      tissue disease.

PMID- 23957996
TI  - Treatment of Becker nevus with topical flutamide.

PMID- 23957997
TI  - Successful treatment of recalcitrant eczematous dermatitis with leflunomide.

PMID- 23957998
TI  - Naturally occurring mastitis disrupts developmental competence of bovine oocytes.
AB  - We examined the effects of naturally occurring mastitis on bovine oocyte
      developmental competence in vitro. Specifically, we investigated the effects of
      intramammary infection on the ovarian pool of oocytes (i.e., follicle-enclosed
      oocytes) and their ability to undergo in vitro maturation, fertilization, and
      further development to the blastocyst stage. Culled Holstein cows (n=50) from 9
      commercial dairy farms in Israel were allotted to 3 groups according to somatic
      cell count (SCC) records of the last 3 monthly milk tests as well as of quarter
      samples collected before slaughter: (1) low SCC (n=7), (2) medium SCC (n=16), or
      (3) high SCC (n=27). Means of SCC values differed among low-, medium-, and high
      SCC groups: 148,000, 311,000 and 1,813,000 cell/mL milk, respectively. Milk yield
      and days in milk did not differ among the 3 groups. Bacterial isolates included
      coagulase-negative staphylococci, Escherichia coli, Streptococcus dysgalactiae,
      or no bacteria found. Ovaries were collected at the abattoir and brought to the
      laboratory. Cumulus oocyte complexes were recovered separately from each cow and
      subjected individually to in vitro maturation and fertilization, followed by 8d
      in culture. The number of aspirated oocytes did not differ among groups, with a
      range of 17 to 21 oocytes per cow. The proportion of oocytes that cleaved into 2-
      to 4-cell-stage embryos (86.1 +/- 3.4%) did not differ among groups. In contrast,
      mean percentages of embryos developed to the blastocyst stage on d 7 and 8 after
      fertilization were less in both medium- and-high SCC groups than in the low-SCC
      group (5.6 +/- 2.3 and 4.1 +/- 1.8 vs. 18.1 +/- 4.6%, respectively). Additional
      analysis indicated that cleavage and blastocyst-formation rates did not differ
      among the bacterial types in the low-, medium-, and high-SCC groups. These are
      the first results to demonstrate that naturally occurring mastitis disrupts the
      developmental competence of the ovarian pool of oocytes, (i.e., oocytes at the
      germinal vesicle stage). The disruption was associated with elevation of SCC
      rather than bacterial type. The results may provide a partial explanation for the
      low fertility of cows that have contracted mastitic pathogens before
      insemination.

PMID- 23957999
TI  - Short communication: Reducing agents attenuate methylglyoxal-based browning in
      Parmesan cheese.
AB  - The microbial production of methylglyoxal in cheese has been linked to the
      formation of brown pigmentation and distinctive volatiles. This study
      investigated methods for preventing methylglyoxal-induced browning in Parmesan
      cheese through the addition of reducing agents. Cheeses were treated with the
      reducing agents sodium bisulfite, glutathione, and erythorbate at 2:1 and 4:1
      molar ratios with added methylglyoxal, and then incubated at 10  degrees C.
      Colorimetric methods were used to determine degree of browning at 0, 3, and 6 d.
      Sodium bisulfite and glutathione inhibited the browning reactions of
      methylglyoxal compared with the control. Erythorbate was much less effective than
      the other compounds at inhibiting browning, yet was significantly less browned
      than the control. These reducing agents are thought to act as strong nucleophiles
      that can form thiohemiketals and thioketals at the carbonyl carbons of
      methylglyoxal.

PMID- 23958000
TI  - Transport phenomena in a model cheese: the influence of the charge and shape of
      solutes on diffusion.
AB  - During cheese ripening, microorganisms grow as immobilized colonies, metabolizing
      substrates present in the matrix and generating products from enzymatic
      reactions. Local factors that limit the rates of diffusion, either within the
      general cheese matrix or near the colonies, may influence the metabolic activity
      of the bacteria during ripening, affecting the final quality of the cheese. The
      objective of this study was to determine the diffusion coefficients of solutes as
      a function of their different physicochemical characteristics (size, charge, and
      shape) in an ultrafiltrate (UF) model cheese (based on ultrafiltered milk) to
      enable better understanding of the ripening mechanisms. Diffusion coefficients of
      fluorescein isothiocyanate (FITC)-dextrans (4 kDa to 2 MDa) and FITC-labeled
      dairy proteins (alpha-lactalbumin, beta-lactoglobulin, and BSA) were measured
      using the technique of fluorescence recovery after photobleaching (FRAP). This
      study showed that macromolecules up to 2 MDa and proteins could diffuse through
      the UF model cheese. The larger FITC-dextrans were not more hindered by the
      structure of the UF model cheese compared with the smaller ones. Any decrease in
      the diffusion coefficients of solutes was related only to their hydrodynamic
      radii. The FITC-dextran diffusion data were fitted to an obstruction model,
      resulting in a constant obstruction factor (k ~0.42). Diffusion in the model
      cheese was sensitive to the physicochemical characteristics of the solute. The
      FITC-dairy proteins studied (rigid and negatively charged molecules) were
      hindered to a greater degree than the FITC-dextrans (flexible and charge-neutral
      molecules) in the UF model cheese. The existence of steric and electrostatic
      interactions between the protein matrix of the UF model cheese and the FITC-dairy
      proteins could explain the decrease in diffusion compared with FITC-dextrans.

PMID- 23958001
TI  - Alterations in milk metabolome and coagulation ability during the lactation of
      dairy cows.
AB  - Milk composition has been known to change during lactation. To help understand
      the changes in metabolic profile throughout the whole lactation, liquid
      chromatography mass-spectrometry was used to analyze 306 milk samples from 82
      primi- and multiparous dairy cows. Changes in metabolic profile common to all
      cows throughout lactation were ascertained based on principal component and
      general linear model analysis. Sets of specific markers; for instance, 225, 397,
      and 641-642 m/z (positive mode), and 186, 241, and 601-604 (negative mode), with
      at least a 1.5-fold higher intensity during the first 60 d compared with the last
      60 d of lactation were observed. The metabolome was affected by parity and
      milking time. Markers, identified as peptides differentiating parity, were
      observed. A significant increase for citrate was observed in evening milk. Milk
      coagulation traits were strongly animal specific. The curd firmness values were
      influenced by milking time. Sets of markers were associated with curd firmness in
      positive (197 m/z) and negative (612, 737, 835, 836, 902, 1000, 1038, and 1079
      m/z) ion mode.

PMID- 23958002
TI  - Meta-analysis of the effect of pasture allowance on pasture intake, milk
      production, and grazing behavior of dairy cows grazing temperate grasslands.
AB  - Daily pasture allowance (PA) is defined as the product of pregrazing pasture mass
      and offered area, and is the major grazing management factor determining pasture
      utilization per unit area and daily performance of grazing dairy cows. The
      objective of the present study was to perform a meta-analysis reviewing the
      effect of PA on pasture intake, milk production, milk composition, and grazing
      behavior of dairy cows. Experiments studying the effect of PA on pasture intake
      or milk production, which eventually included milk composition or grazing
      behavior data, or both, were selected to create a database. Papers were selected
      only if at least 2 PA were compared under the same experimental conditions,
      particularly the same pasture mass (i.e., where PA levels were only obtained
      through changes in daily offered area). The final database included 97 PA
      comparisons reported in 56 papers. For analytical purposes, the database was
      subdivided into 3 subsets that varied according to the estimation height (EH) at
      which PA was determined; that is, PA above ground level (PA0 subset), PA above
      2.5 to 3.5 cm (PA3 subset), and PA above 4 to 5 cm (PA5 subset). Statistical
      analyses were conducted independently on the PA0, PA3, and PA5 subsets and on the
      whole database (global analysis) by using linear and nonlinear mixed-model
      procedures. The curves, either exponential, quadratic, or linear, describing the
      effects of PA on pasture intake, milk production, or grazing behavior of dairy
      cows are conceptually similar, whatever the EH. The equations describing these
      curves are, however, specific for each EH. Accordingly, from typical low to high
      PA, the increase in pasture intake (0.13 vs. 0.21 vs. 0.28 kg/kg of PA), milk
      production (0.11 vs. 0.17 vs. 0.24 kg/kg of PA), and milk solids production
      (0.008 vs. 0.010 vs. 0.013 kg/kg of PA) per kilogram of increase in PA was lower
      for PA0 than for PA3, and for PA3 than for PA5. Grazing time increased from low
      to medium PA and did not vary from medium to high PA. Pasture intake rate seemed
      to increase from low to medium PA because of greater bite mass, whereas it
      increased from medium to high PA because of greater biting rate. The present meta
      analysis demonstrated that the general relationship between PA and any dependent
      variable is quite strong and independent of EH. This suggests no specific
      relationship for some parts of the world or methodology approach, with a high
      portability of the global equations calculated here. These results are useful for
      improving grazing management and modeling on pasture-based dairy systems.

PMID- 23958003
TI  - Rate of transmission: a major determinant of the cost of clinical mastitis.
AB  - The aim of this research was to use probabilistic sensitivity analysis to
      evaluate the relative importance of different components of a model designed to
      estimate the cost of clinical mastitis (CM). A particular focus was placed on the
      importance of pathogen transmission relative to other factors, such as milk price
      or treatment costs. A stochastic Monte Carlo model was developed to simulate a
      case of CM at the cow level and to calculate the associated costs for 5 defined
      treatment protocols. The 5 treatment protocols modeled were 3 d of antibiotic
      intramammary treatment, 5 d of antibiotic intramammary treatment, 3 d of
      intramammary and systemic antibiotic treatment, 3d of intramammary and systemic
      antibiotic treatment plus 1 d of nonsteroidal antiinflammatory drug treatment,
      and 5 d of intramammary and systemic antibiotic treatment. Uniform distributions
      were used throughout the model to enable investigation of the cost of CM over a
      spectrum of clinically realistic scenarios without specifying which scenario was
      more or less likely. A risk of transmission parameter distribution, based on
      literature values, was included to model the effect of pathogen transmission to
      uninfected cows, from cows that remained subclinically infected after treatment
      for CM. Spearman rank correlation coefficients were used to evaluate the
      relationships between model input values and the estimated cost of CM. Linear
      regression models were used to explore the effect that changes to specific
      independent variables had on the cost of CM. Risk of transmission was found to
      have the strongest association with the cost of CM, followed by bacteriological
      cure rate, cost of culling, and yield loss. Other factors such as milk price,
      cost of labor, and cost of medicines were of minimal influence in comparison. The
      cost of CM was similar for all 5 treatment protocols. The results from this study
      suggest that, when seeking to minimize the economic impact of CM in dairy herds,
      great emphasis should be placed on the reduction of pathogen transmission from
      cows with CM to uninfected cows.

PMID- 23958004
TI  - Feeding a C16:0-enriched fat supplement increased the yield of milk fat and
      improved conversion of feed to milk.
AB  - Previous work has indicated that dietary palmitic acid (C16:0) may increase milk
      fat yield. The effect of a dietary C16:0-enriched fat supplement on feed intake,
      yield of milk and milk components, and feed efficiency was evaluated in an
      experiment with a crossover arrangement of treatments with 25-d periods. A
      fermentable starch challenge on the last 4d of each period was utilized as a
      split-plot within period. Sixteen mid-lactation Holstein cows (249 +/- 33 d in
      milk) were assigned randomly to treatment sequence. Treatments were either a
      C16:0-enriched (~85% C16:0) fat supplement (fatty acid treatment, FAT, 2% dry
      matter) or a control diet (CON) containing no supplemental fat. Diets containing
      dry ground corn grain were fed from d 1 through 21 of each period. On the last 4d
      of each period, dry ground corn was replaced by high-moisture corn grain on an
      equivalent dry matter basis to provide a fermentable starch challenge. Response
      variables were averaged for d 18 to 21 (immediately before the fermentable starch
      challenge) and d 22 to 25 (during the fermentable starch challenge). We observed
      no treatment effects on milk yield or milk protein yield. The FAT treatment
      increased milk fat concentration from 3.88 to 4.16% and fat yield from 1.23 to
      1.32 kg/d compared with CON. The FAT treatment decreased dry matter intake by 1.4
      kg/d and increased conversion of feed to milk (3.5% fat-corrected milk yield/dry
      matter intake) by 8.6% compared with CON. The increase in milk fat yield by FAT
      was entirely accounted for by a 27% increase in 16-carbon fatty acid output into
      milk. Yields of de novo and preformed fatty acids were not affected by FAT
      relative to CON. The fermentable starch challenge did not affect milk fat
      concentration or yield. Results demonstrate the potential for a dietary C16:0
      enriched fat supplement to improve milk fat concentration and yield as well as
      efficiency of conversion of feed to milk. Further studies are required to verify
      and extend these results and to determine whether responses are similar across
      different diets and levels of milk production.

PMID- 23958005
TI  - Color Doppler flow imaging for the early detection of nonpregnant cattle at 20
      days after timed artificial insemination.
AB  - The objective was to determine the accuracy of a pregnancy test for predicting
      nonpregnant cattle based on the evaluation of corpus luteum (CL) blood flow at 20
      d (CLBF-d20) after timed artificial insemination (TAI). Crossbred Holstein-Gir
      dairy heifers (n=209) and lactating cows (n=317) were synchronized for TAI using
      the following protocol: intravaginal implant (1.0 g of progesterone) and 2mg of
      estradiol benzoate i.m. on d -10, implant removal and 0.526 mg of sodium
      cloprostenol i.m. on d -2, 1mg of estradiol benzoate i.m. on d -1, and TAI on d
      0. On d 20, animals underwent grayscale ultrasonography (US) to locate the CL and
      color flow Doppler to evaluate CLBF-d20 using a portable ultrasound equipped with
      a 7.5-MHz rectal transducer. Based only on a visual, subjective CLBF evaluation,
      the animals were classified as pregnant or not pregnant. On d 30 to 35, blinded
      from results of the previous diagnosis, the same operator performed a final
      pregnancy diagnosis using US to visualize the fetal heartbeat (gold standard; US
      d30). A second evaluator also analyzed the CLBF-d20 in the same animals by
      watching 7-s recorded videos. Blood samples were collected from a subset of 171
      females to determine, by RIA, plasma progesterone (P4) concentrations, which
      indicate CL function. The final pregnancy outcome (US-d30) was retrospectively
      compared with the CLBF-d20 diagnoses and then classified either as correct or
      incorrect. The number of true positive, true negative, false positive, and false
      negative decisions were inserted into a 2 * 2 decision matrix. The sensitivity,
      specificity, positive predictive value, negative predictive value, and accuracy
      of the CLBF-d20 test were calculated using specific equations. Binomial variables
      (pregnancy rate and proportions) were analyzed using Fisher's exact test for the
      effect of parity and to compare between evaluators and tests (CLBF-d20 vs. plasma
      P4). The kappa values were calculated to quantify the agreement between CLBF-d20
      and the gold standard (US-d30) and between evaluators. The performance parameters
      of CLBF-d20 test were as follows: sensitivity=99.0%, specificity=53.7%, positive
      predictive value=65.1%, negative predictive value=98.5%, and accuracy=74.8%.
      False negatives represented only 0.4% of the exams. No differences existed in
      these parameters between evaluators (no. 1 vs. no. 2) and tests (CLBF-d20 vs.
      plasma P4). Moreover, a high level of agreement was observed between evaluators
      (0.91). In conclusion, visual evaluation of CLBF-d20 represents a quick,
      reliable, and consistent diagnostic test that enables the early detection of
      nonpregnant cattle.

PMID- 23958006
TI  - Prediction models of silage fermentation products on crop composition under
      strict anaerobic conditions: a meta-analysis.
AB  - A meta-analysis was conducted to establish linkages between crop and fermentation
      variables. Data from well-controlled mini silage studies were used in which no
      additives had been used and no ingress of air had occurred. The silage set
      consisted of data on crop chemical composition and epiphytic lactic acid bacteria
      count, and fermentation products (organic acids, alcohols, and ammonia-N) from
      118 silages made from 30 grass, 7 legume, 15 grass and legume mixtures, and 66
      whole-crop maize samples. The prediction models for fermentation products on crop
      variables were obtained by stepwise multiple regression analysis. Perennial
      forage and maize silages were analyzed separately. The best models were obtained
      for acetic acid in perennial forage silages, with a coefficient of determination
      of 0.63, and for lactic acid and ethanol in whole-crop maize silages, with
      coefficients of determination of 0.84 and 0.61, respectively. Fermentation
      products of perennial forage and maize silages were best related to dry matter
      and crude protein contents, respectively. Overall, the prediction equations were
      weak. 

PMID- 23958007
TI  - Effects of prolonged nutrient restriction on baseline and periprandial plasma
      ghrelin concentrations of postpubertal Holstein heifers.
AB  - Objectives of this study were to measure both daily and periprandial plasma
      ghrelin concentrations of postpubertal Holstein heifers during prolonged
      undernutrition. Following an acclimation period, Holstein heifers [n=10; 339.5 +/
      8.6 kg of body weight (BW)] were fed ad libitum [well fed (WF); n=5] or
      restricted to 50% of ad libitum intake [underfed (UF); n=5) for 8 wk. Body
      condition scores (BCS) were recorded at the beginning and end of the treatment
      period, and weekly measurements of BW, plasma ghrelin, progesterone, and
      nonesterified fatty acids (NEFA) concentrations were obtained. Ovarian follicular
      and luteal structures were measured twice weekly via transrectal ultrasonography.
      Plasma ghrelin concentrations were also measured during a periprandial window
      bleed conducted at the end of the experiment. During the window bleed, samples
      were collected every 15 min between 0500 and 0900 h, with feed offered at 0700 h.
      Underfed heifers lost BW and BCS, whereas WF heifers gained weight and either
      increased or maintained BCS. Chronic underfeeding increased circulating ghrelin
      and NEFA concentrations. By wk 4 of the treatment period, circulating ghrelin
      concentrations of the UF heifers reached a plateau. Periprandial fluctuations in
      ghrelin concentrations were apparent as plasma ghrelin concentrations changed
      over time. Overall differences in periprandial plasma ghrelin concentrations were
      primarily due to prefeeding effects of plane of nutrition. Plasma ghrelin
      concentrations and change in BCS were negatively correlated such that heifers
      that lost the most BCS had the highest concentrations of circulating ghrelin. Two
      of the 5 UF heifers became anestrus by wk 3 of the treatment period. Despite
      being of similar age, the heifers that became anestrus had lower BW and plasma
      ghrelin concentrations than the UF heifers that continued to ovulate. In the
      current experiment, long-term undernutrition elicited ghrelin responses similar
      to those reported for shorter durations of nutrient restriction in cattle and
      other ruminants. These results demonstrate that plane of nutrition is a chronic
      regulator of plasma ghrelin concentrations, and that these concentrations can be
      experimentally manipulated in postpubertal heifers for up to 8 wk with no
      evidence of an adaptive response.

PMID- 23958008
TI  - Invited review: Caseins and the casein micelle: their biological functions,
      structures, and behavior in foods.
AB  - A typical casein micelle contains thousands of casein molecules, most of which
      form thermodynamically stable complexes with nanoclusters of amorphous calcium
      phosphate. Like many other unfolded proteins, caseins have an actual or potential
      tendency to assemble into toxic amyloid fibrils, particularly at the high
      concentrations found in milk. Fibrils do not form in milk because an alternative
      aggregation pathway is followed that results in formation of the casein micelle.
      As a result of forming micelles, nutritious milk can be secreted and stored
      without causing either pathological calcification or amyloidosis of the mother's
      mammary tissue. The ability to sequester nanoclusters of amorphous calcium
      phosphate in a stable complex is not unique to caseins. It has been demonstrated
      using a number of noncasein secreted phosphoproteins and may be of general
      physiological importance in preventing calcification of other biofluids and soft
      tissues. Thus, competent noncasein phosphoproteins have similar patterns of
      phosphorylation and the same type of flexible, unfolded conformation as caseins.
      The ability to suppress amyloid fibril formation by forming an alternative
      amorphous aggregate is also not unique to caseins and underlies the action of
      molecular chaperones such as the small heat-shock proteins. The open structure of
      the protein matrix of casein micelles is fragile and easily perturbed by changes
      in its environment. Perturbations can cause the polypeptide chains to segregate
      into regions of greater and lesser density. As a result, the reliable
      determination of the native structure of casein micelles continues to be
      extremely challenging. The biological functions of caseins, such as their
      chaperone activity, are determined by their composition and flexible conformation
      and by how the casein polypeptide chains interact with each other. These same
      properties determine how caseins behave in the manufacture of many dairy products
      and how they can be used as functional ingredients in other foods. 

PMID- 23958009
TI  - Effects of short-term variation in forage quality and forage to concentrate ratio
      on lactating dairy cows.
AB  - Within-farm variation in forage composition can be substantial and potentially
      costly, and it presents challenges for sampling the forage accurately. We
      hypothesized that day-to-day variation in forage neutral detergent fiber (FNDF)
      concentrations and diet variation caused by sampling error would have negative
      effects on production measures in lactating dairy cows. Twenty-four Holstein cows
      (73 d in milk) were used in 8 replicated 3 * 3 Latin squares with 21-d periods.
      Treatments were (1) control (CON), (2) variable (VAR), and (3) overreacting
      (ORR). On average, over the 21-d period, all 3 treatments were the same [24.7%
      FNDF and 48.2% forage dry matter (DM) composed of 67% alfalfa silage and 33%
      grass silage]. The CON treatment was essentially consistent day-to-day in total
      forage and FNDF concentrations and proportion of alfalfa and grass silages. The
      VAR treatment changed daily (in a random pattern) in proportion of alfalfa and
      grass silages fed, which resulted in day-to-day changes in FNDF (range was 21.5
      to 28%). The ORR treatment varied in a 5-d cyclic pattern in total forage and
      FNDF concentrations (26, 24, 28, and 21.5% FNDF). Over the 21 d, ORR (25.1 kg/d)
      had higher DM intake compared with CON (24.5 kg/d) and VAR (24.3 kg/d). Milk
      production (42.8 kg/d), milk fat (3.5%), and milk protein (2.8%) were not
      affected by treatment; however, a treatment * day interaction was observed for
      milk production. Lower daily milk yields for VAR and ORR compared with CON were
      rare; they only followed sustained 4- and 5-d periods of feeding higher FNDF
      diets compared with CON. In contrast, increased daily milk yields for VAR and ORR
      versus CON were more frequent and followed sustained diet changes of only 2 or
      3d. Lipolytic and lipogenic-related enzyme mRNA abundances in subcutaneous
      adipose tissue were not affected by treatment. Treatment * day interactions were
      observed for milk fatty acid markers of cellulolytic bacteria (iso-14:0, iso
      15:0, iso-16:0) and lipolysis (18:0) and generally followed the expected response
      to changes in daily rations. Overall, extreme daily fluctuations in FNDF had no
      cumulative negative effect on production measures over a 21-d period, and daily
      responses to transient increases in FNDF were less than expected.

PMID- 23958010
TI  - Physiological responses and lactational performances of late-lactation dairy
      goats under heat stress conditions.
AB  - Eight Murciano-Granadina dairy goats in late lactation were exposed to different
      ambient conditions, using metabolic cages in a climatic chamber. The experimental
      design was a crossover (2 periods of 35 d and 4 goats each) and conditions were
      (1) thermal neutral (TN; 15 to 20  degrees C day-night) and (2) heat stress (HS;
      12-h day at 37  degrees C and 12-h night at 30.5  degrees C). Humidity was
      maintained at 40% and light-dark was constant (12-12h). The forage:concentrate
      ratio was adjusted daily for maintaining similar value in TN and HS goats
      (70:30). Water was freely available at ambient temperature. Rectal temperature
      and respiratory rate (0800, 1200 and 1700 h) and milk yield were recorded daily,
      whereas milk composition, nonesterified fatty acids and haptoglobin in blood were
      analyzed weekly. At d 25, additional blood samples were taken for analysis of
      metabolites and indicators of the acid-base balance. Digestibility coefficients
      and N balance were determined (d 31 to 35) and body weight was recorded (d 35).
      Compared with TN goats, HS goats experienced greater rectal temperature (+0.58 
      degrees C), respiratory rate (+48 breaths/min), water intake (+77%) and water
      evaporation (+207%). Intake of HS goats rapidly declined until d 7 (-40%),
      partially recovered from d 7 to 19, and steadied thereafter (-14%). No changes in
      digestibility or N balance were detected. Blood nonesterified fatty acids and
      haptoglobin peaked at d 7 in HS goats but did not vary thereafter. Although milk
      yield did not vary by treatment, milk of HS goats contained -12.5% protein and 
      11.5% casein than TN goats. Panting reduced concentration and pressure of CO2 in
      the blood of HS goats, but they were able to maintain their blood pH similar to
      the TN group by lowering HCO3(-) and increasing Cl(-) concentrations in their
      blood. In conclusion, HS dairy goats showed dramatic physiological changes during
      the first week of treatment and partially recovered thereafter. They were able to
      maintain milk yield by losing body mass, but milk protein content and protein
      yield were depressed. Further research is needed to assess the response of dairy
      goats to HS at earlier stages of lactation.

PMID- 23958011
TI  - Expanding the dairy herd in pasture-based systems: the role of sexed semen use in
      virgin heifers and lactating cows.
AB  - A model was developed to examine the effects of sexed semen use in virgin heifers
      and lactating cows on replacement heifer numbers and rate of herd expansion in a
      seasonal dairy production system. Five separate herds were established according
      to the type of semen used: conventional frozen-thawed (Conv), sexed fresh semen
      used in lactating cows for the first 3 wk of the breeding season (SFre1), sexed
      frozen-thawed semen used in lactating cows for the first 3 wk of the breeding
      season (SFro1), sexed fresh semen used in lactating cows for the first 6 wk of
      the breeding season (SFre2), or sexed frozen-thawed semen used in lactating cows
      for the first 6 wk of the breeding season (SFro2). In the SFro1, SFre1, SFro2,
      and SFre2 herds, sexed semen was used for the first and second artificial
      insemination in virgin heifers. Pregnancy rates achieved with sexed fresh and
      sexed frozen-thawed semen were assumed to be 94 and 75% of those achieved with
      conventional frozen-thawed semen, respectively. Initial herd size was 100 cows,
      which was maintained for the first 2 yr of the 15-yr simulation, after which all
      available replacement heifers were retained to facilitate herd expansion. Two
      different scenarios of land availability were examined for each of the 5 herds:
      land available allowed expansion to a maximum herd size of 150 cows (S1), or land
      available allowed expansion to a maximum herd size of 300 cows (S2). Once maximum
      herd size was reached, sexed semen use was discontinued and all excess heifer
      calves were sold at 1 mo old. All capital expenditure associated with expansion
      was financed with a 15-yr loan. Each of the 10 different options was evaluated in
      terms of annual farm profit, annual cash flow, and total discounted net profit.
      The use of fresh sexed semen generated more replacement heifers, leading to
      faster herd expansion compared with frozen-thawed sexed semen and conventional
      frozen-thawed semen. Maximum herd size under S1 was reached in yr 5, 5, 4, 5, and
      7 for the SFre1, SFro1, SFre2, SFro2, and Conv herds, respectively. Under S2,
      maximum herd size was reached in yr 8, 10, 7, 9, and 14 for the SFre1, SFro1,
      SFre2, SFro2, and Conv herds, respectively. Total discounted net profit under S1
      for the SFre2 herd was ?4,130, ?38,869, ?47,231, and ?52,089 greater compared
      with the SFre1, SFro1, Conv, and SFro2 herds, respectively. Under S2, discounted
      net profit for the SFre2 herd was ?44,204, ?255,524, ?280,373, and ?325,815
      greater compared with the SFre1, SFro1, SFro2, and Conv herds, respectively. The
      negative effects of the sexed frozen-thawed semen on herd fertility reduced farm
      profitability and will prevent its widespread use in lactating cows. 

PMID- 23958013
TI  - Validating the accuracy of activity and rumination monitor data from dairy cows
      housed in a pasture-based automatic milking system.
AB  - Behavioral observations are important in detecting illness, injury, and
      reproductive status as well as performance of normal behaviors. However,
      conducting live observations in extensive systems, such as pasture-based dairies,
      can be difficult and time consuming. Activity monitors, such as those created for
      use with automatic milking systems (AMS), have been developed to automatically
      and remotely collect individual behavioral data. Each cow wears a collar
      transponder for identification by the AMS, which can collect data on individual
      activity and rumination. The first aim of this study was to examine whether cow
      activity levels as reported by the AMS activity monitor (ACT) are accurate
      compared with live observations and previously validated pedometers [IceQube
      (IQ), IceRobotics, Edinburgh, UK]. The second aim of the study was to determine
      if the AMS rumination monitors (RUM) provide an accurate account of time spent
      ruminating compared with live observations. Fifteen lactating Holstein cows with
      pasture access were fitted with ACT, RUM, and IQ. Continuous focal observations
      (0600-2000 h) generated data on lying and active behaviors (standing and
      walking), as well as rumination. Activity recorded by live observation and IQ
      included walking and standing, whereas IQ steps measured cow movement (i.e.,
      acceleration). Active behaviors were analyzed separately and in combination to
      ascertain exactly what behavioral components contributed to calculation of ACT
      "activity." Pearson correlations (rp) were computed between variables related to
      ACT, RUM, IQ, and live observations of behavior. A linear model was used to
      assess significance differences in the correlation coefficients of the 4 most
      relevant groups of variables. Significant but moderate correlations were found
      between ACT and observations of walking (r(p)=0.61), standing (r(p)=0.46), lying
      (r(p)=-0.57), and activity (r(p)=0.52), and between ACT and IQ steps (r(p)=0.75)
      and activity (r(p)=0.58) as well as between RUM and observations of rumination
      (rp=0.65). These data indicate that ACT and RUM do reflect cow walking and
      rumination, respectively, but not with a high degree of accuracy, and lying
      cannot be distinguished from standing.

PMID- 23958012
TI  - Short communication: a comparison of 2 nonsteroidal antiinflammatory drugs
      following the first stage of a 2-stage fistulation surgery in dry dairy cows.
AB  - Postoperative pain and its management following fistulation surgery in cattle are
      poorly understood. The purpose of this study was to compare 2 nonsteroidal
      antiinflammatory drugs (NSAID) as potential postoperative pain management
      treatments following the first stage of a 2-stage fistulation surgery. A
      randomized complete block design trial was conducted in dry Holstein cows (n=10)
      following fistulation surgery. Ketoprofen (3mg/kg of body weight i.m.) was
      administered on the day of surgery and 24 h later, whereas meloxicam (0.5 mg/kg
      of body weight s.c.) was administered once only on the day of surgery. Outcomes
      evaluated at 0, 2, 9, 24, 26, and 33 h postsurgery were heart rate, respiration
      rate, rectal temperature, and infrared temperature around the surgical site.
      Outcomes evaluated on the day of surgery and d 1 following surgery and compared
      with the average for the 4d before surgery were lying activity (total lying time,
      total time spent lying on the left side, and percentage of time lying on the left
      side) and feed intake. A difference was observed in dry matter intake on d 1 but
      this effect was not different on d 0 compared with presurgical averages. A
      difference was observed in time spent lying on the left side and a difference was
      observed in heart rate following the first stage of fistulation surgery compared
      with presurgical averages. The infrared temperature readings around the surgical
      site were significantly greater in the hours following surgery compared with
      presurgical averages. The respiration rate increased over time after 24h
      postsurgery compared with presurgical values. Although it was clear that the
      surgery is painful, the drug effects were more difficult to explain. On d 0 and
      1, the meloxicam-treated cows ate 3 kg more but spent 101 min/d less time lying
      on their left side compared with ketoprofen-treated cows. The first stage of a 2
      stage fistulation surgery was considered painful based on changes in heart rate,
      respiration rate, infrared temperature readings, dry matter intake, and time
      spent lying on the left side. It is clear that left flank surgery is painful and
      that NSAID can improve outcomes associated with that pain, but we cannot make
      recommendations as to which NSAID to choose based on these results.

PMID- 23958014
TI  - The effect of food location, heat load, and intrusive medical procedures on
      brushing activity in dairy cows.
AB  - Animals allocate time and effort to a range of core (e.g., sleeping, feeding,
      drinking) and "luxury" (e.g., playing, exploring) activities. A luxury activity
      is characterized by low resilience and, as such, will be reduced when time or
      energy resources are limited, including under conditions of stress or discomfort.
      One seemingly luxurious activity available to cows on an increasing number of
      dairy farms is rubbing against an automated brush. The current study examined the
      effect of distance from food, heat load, and an intrusive medical procedure
      (i.e., artificial insemination and transrectal pregnancy examination) on the
      resilience of brush usage. The probability of using the brush decreased
      significantly when food was located distantly from the brush (mean=0.53) compared
      with days when food was located closer to the brush (mean=0.81). Brush usage also
      decreased at high temperature and humidity levels, with an average decrease of
      0.062 brushing events for an increase of 1 temperature-humidity index unit (95%
      confidence interval=-0.93-0.030). In addition, a significant reduction of
      approximately 50% in brushing activity was observed on days of artificial
      insemination compared with the preceding 3d and the following 3d. These findings
      show that brush usage is a low resilience activity that reduces under a range of
      conditions. It may thus have the potential to be used as an indicator of a range
      of health and welfare problems in cows. Further research should be conducted to
      assess the sensitivity and specificity of this suggested tool and its possible
      contribution to the early detection of morbidity. 

PMID- 23958015
TI  - Thin and fat cows, and the nonlinear genetic relationship between body condition
      score and fertility.
AB  - Thin and fat cows are often credited for low fertility, but body condition score
      (BCS) has been traditionally treated as a linear trait when genetic correlations
      with reproductive performance have been estimated. The aims of this study were to
      assess genetic parameters for fertility, production, and body condition traits in
      the Brown Swiss population reared in the Alps (Bolzano-Bozen Province, Italy),
      and to investigate the possible nonlinearity among BCS and other traits by
      analyzing fat and thin cows. Records of BCS measured on a 5-point scale were
      preadjusted for year-season and days in milk at scoring, and were considered
      positive (1) for fat cows if they exceeded the value of 1 residual standard
      deviation or null (0) otherwise, whereas positive values for thin cows were
      imputed to records below -1 residual standard deviation. Fertility indicators
      measured on first- and second-parity cows were interval from parturition to first
      service, interval from first service to conception, interval from parturition to
      conception, number of inseminations to conception, conception at first service,
      and nonreturn rate at 56 d after first service. Production traits were peak milk
      yield, lactation milk yield, and lactation length. Data were from 1,413 herds and
      included 16,324 records of BCS, fertility, and production for first-parity, and
      10,086 fertility records for second-parity cows. Animals calved from 2002 to 2007
      and were progeny of 420 artificial insemination bulls. Genetic parameters for the
      aforementioned traits were obtained under univariate and bivariate threshold and
      censored linear sire models implemented in a Bayesian framework. Posterior means
      of heritabilities for BCS, fat cows, and thin cows were 0.141, 0.122, and 0.115,
      respectively. Genetic correlations of body condition traits with contemporary
      production were moderate to high and were between -0.556 and 0.623. Body
      condition score was moderately related to fertility in first (-0.280 to 0.497)
      and second (-0.392 to 0.248) lactation. The fat cow trait was scarcely related to
      fertility, particularly in first-parity cows (-0.203 to 0.281). Finally, the
      genetic relationships between thin cows and fertility were higher than those
      between BCS and fertility, both in first (-0.456 to 0.431) and second (-0.335 to
      0.524) lactation. Body condition score can be considered a predictor of
      fertility, and it could be included in evaluation either as linear measure or as
      thin cow. In the second case, the genetic relationship with fertility was
      stronger, exacerbating the poorest body condition and considering the possible
      nonlinearity between fertility and energy reserves of the cow.

PMID- 23958016
TI  - Induction of and recovery from milk fat depression occurs progressively in dairy
      cows switched between diets that differ in fiber and oil concentration.
AB  - Milk fat depression (MFD) caused by intermediates of ruminal biohydrogenation
      commonly occurs in dairy cattle. The time course of recovery from MFD is
      important to mechanistic investigation and management of the condition. Nine cows
      were used in a repeated design, allowing analysis of recovery from diet-induced
      MFD. A high-fiber, low-oil diet was fed during the control and recovery periods,
      and a low-fiber, high-oil (LFHO) diet was fed during the induction period. Milk
      yield was not affected by treatment. Milk fat percentage and yield decreased
      progressively during induction and were lower by d 3 and 5, respectively. Milk
      fat concentration and yield increased progressively when cows were fed the
      recovery diet and were not different from control on d 19 and 15, respectively.
      Yield of de novo synthesized fatty acids (FA) decreased progressively during the
      induction period and was lower than that of controls by d 5. A biphasic response
      was seen for milk fat trans isomers, where trans-11 C18:1 and cis-9,trans-11
      conjugated linoleic acid (CLA) were elevated initially and trans-10 C18:1 and
      trans-10,cis-12 CLA increased progressively during the induction period. A
      similar biphasic response was seen during recovery from MFD, with trans-10 C18:1
      and trans-10,cis-12 rapidly decreasing initially and trans-11 C18:1 and cis
      9,trans-11 CLA increasing slightly above control levels during the second phase.
      Recovery from diet-induced MFD occurs gradually with a short lag when dietary
      fiber and oil concentrations are corrected. This time course provides a framework
      to identify factors causing MFD and set expectations during recovery from MFD. 

PMID- 23958017
TI  - Noninferiority trial comparing a first-generation cephalosporin with a third
      generation cephalosporin in the treatment of nonsevere clinical mastitis in dairy
      cows.
AB  - The objective of this study was to evaluate the noninferiority of 2 intramammary
      treatments for nonsevere clinical mastitis. The 2 treatments were a first
      generation cephalosporin (cephapirin sodium, 2 treatments 12h apart) and a third
      generation cephalosporin (ceftiofur hydrochloride, treatments once a day for 5d).
      A total of 296 cases on 7 farms met the enrollment criteria for the study.
      Streptococcus dysgalactiae was the most common bacterial species identified in
      milk samples from cows with mild to moderate clinical mastitis, followed by
      Escherichia coli, other esculin-positive cocci, Streptococcus uberis, and
      Klebsiella spp. Treatment was randomly allocated as either cephapirin sodium or
      ceftiofur hydrochloride via intramammary infusion according to label standards.
      Bacteriological cure was defined based on 2 posttreatment milk samples taken at
      10 and 17d after enrollment. Noninferiority of cephapirin relative to ceftiofur
      was shown for bacteriological cure of gram-positive cases and for clinical cure
      of all cases. Ceftiofur showed a significantly higher bacteriological cure in
      gram-negative cases. Treatments showed no significant difference in
      bacteriological cure of all cases and in time to exit from the study, where the
      absence of a difference does not imply noninferiority. Based on the findings from
      this study, farm-specific treatment protocols that differ for gram-positive and
      gram-negative cased may be developed. 

PMID- 23958018
TI  - The effect of Protexin on prevention of ileocecal infection by Mycobacterium
      avium subspecies paratuberculosis in dairy calves.
AB  - The objective of this study was to evaluate the effect of Protexin (Probiotics
      International Ltd., South Petherton, UK) in the prevention of ileocecal infection
      by Mycobacterium avium ssp. paratuberculosis (MAP) in dairy calves in the field
      situation. Forty Holstein bull calves whose dams were paratuberculosis negative
      (confirmed by serum ELISA test and fecal nested PCR) were randomly selected in 2
      groups. All calves were fed raw milk collected from the bulk tank in a
      paratuberculosis-infected dairy farm, which was confirmed by PCR. The treatment
      group (20 calves) was given 2 g of Protexin from birth until weaning (90 d). The
      control group (20 calves) did not consume Protexin. The calves were culled at 12
      mo of age and the ileocecal lymph nodes were sampled. The lymph nodes were tested
      by nested PCR to evaluate MAP infection. In the treatment group, 2 out of 20 calf
      (10%) ileoceca were infected by MAP, whereas in the control group, 8 out of 20
      calf (40%) ileoceca were infected by MAP. A significant difference existed
      between ileocecal infection by MAP in treatment and control groups. Thus,
      Protexin showed a significant effect in decreasing the ileocecal infection by
      MAP.

PMID- 23958019
TI  - Corn silage hybrid type and quality of alfalfa hay affect dietary nitrogen
      utilization by early lactating dairy cows.
AB  - This experiment was conducted to determine the effects of corn silage (CS)
      hybrids and quality of alfalfa hay (AH) in high-forage dairy diets on N
      utilization, ruminal fermentation, and lactational performance by early-lactating
      dairy cows. Eight multiparous Holstein cows were used in a duplicated 4 * 4 Latin
      square experiment with a 2 * 2 factorial arrangement of dietary treatments. The 8
      cows (average days in milk = 23 +/- 11.2) were surgically fitted with ruminal
      cannula, and the 2 squares were conducted simultaneously. Within square, cows
      were randomly assigned to a sequence of 4 diets: conventional CS (CCS) or brown
      midrib CS (BMR) was combined with fair-quality AH [FAH: 46.7% neutral detergent
      fiber (NDF) and 18.4% crude protein (CP)] or high-quality AH (HAH: 39.2% NDF and
      20.7% CP) to form 4 treatments: CCS with FAH, CCS with HAH, BMR with FAH, and BMR
      with HAH. Diets were isonitrogenous across treatments, averaging 15.9% CP. Each
      period lasted a total of 21 d, with 14 d for treatment adaptation and 7d for data
      collection and sampling. Intake of DM and milk yield did not differ in response
      to CS hybrids or AH quality. Although feeding BMR-based diets decreased urinary N
      output by 24%, it did not affect fecal N output. Feeding HAH decreased urinary N
      output by 15% but increased fecal N output by 20%. Nitrogen efficiency [milk N
      (g/d)/intake N (g/d)] tended to increase for BMR treatments. Ruminal ammonia-N
      concentration was lower for cows fed BMR-based diets than for those fed CCS-based
      diets but was not affected by quality of AH. Feeding BMR-based diets or HAH
      decreased milk urea N concentration by 23 or 15%, respectively, compared with CCS
      based diets or FAH. Total volatile fatty acid concentration increased with HAH
      but was not influenced by CS hybrids. Feeding BMR-based diets decreased urinary N
      to-fecal N ratio (UN:FN), and it was further reduced by feeding HAH. Although
      cows fed the BMR-based diets tended to increase milk N-to-manure N ratio, the
      quality of AH did not affect the ratio. The lower ratio of UN:FN with a higher
      ratio of milk N-to-manure N ratio for the BMR-based diets indicates that feeding
      BMR may reduce manure ammonia-N by reducing excretion of urinary N and increasing
      secretion of milk N per unit of manure N excreted.

PMID- 23958020
TI  - The effect of increasing the nutrient and amino acid concentration of milk diets
      on dairy heifer individual feed intake, growth, development, and lactation
      performance.
AB  - Increasing early (<3 mo) nutrient feeding levels and growth rate of dairy calves
      has been found to increase their milk production potential. The objective of this
      study was to compare the effect of offering milk diets with or without added
      carbohydrates and amino acids on calf growth, weaning age, and subsequent growth
      and milk yield of dairy heifers in their first lactation. Friesian calves born at
      Massey University (n=57) were selected at random, weighed, and allocated to
      receive 1 of 3 diets. All calves were fed colostrum from 1 to 3d of age, followed
      by 4 L of whole milk (WM) per head per day and probiotics between 3 and 18d of
      age. At 18d of age, calves were weighed to ensure mean body weight (BW); then, at
      19 d of age, calves changed diets to 1 of 3 treatments, which reached full
      treatment rate at 21 d of age. The diets were 4 L/head per day of WM (M); 4
      L/head per day of WM plus 200 g of plant carbohydrates (MP); and 4 L/head per day
      of WM plus 200 g of plant carbohydrates with amino acids (MPA). Calves were
      weaned upon reaching a BW of 90 kg. During this period, BW, body condition, and
      hip height and width were measured. The heifers were commingled and grazed on
      ryegrass and white clover pastures until calving at 23 mo of age, when BW, body
      condition, and hip height and width were measured again. Milk yield and
      composition were measured throughout first lactation. At weaning, calves fed MPA
      had greater mean BW gain, a lower number of days to target BW, and a greater mean
      hip width gain compared with calves in the M group, although mean gain in hip
      height did not differ among treatments. Total calf starter intake during the milk
      period was lower for MPA-fed calves compared with those offered M, mainly due to
      a shorter milk feeding period required to attain the 90-kg weaning weight,
      whereas mean daily starter intake and straw intake did not differ. No difference
      was observed in the calving rate or calving age of heifers in any of the dietary
      feeding groups. First lactation fat-corrected milk yield, milk fat percentage,
      and total milk fat and protein yields were greater for animals reared on MP and
      MPA compared with M. Body weight, hip height and width at parturition, milk
      protein percentage, somatic cell count, or days in milk did not differ among
      treatments. Increasing nutrient intake, during the milk feeding period, improved
      the BW gain of calves and milk production of dairy heifers during first
      lactation.

PMID- 23958021
TI  - Molecular structure, chemical and nutrient profiles, and metabolic
      characteristics of the proteins and energy in new cool-season corn varieties
      harvested as fresh forage for dairy cattle.
AB  - To our knowledge, no previous research exists concerning the molecular structure
      and metabolic characteristics of the proteins and energy that new cool-season
      corn varieties provide for dairy cattle. The objectives of this study were to
      identify the differences in the molecular structures of proteins among several
      new cool-season corn varieties [Pioneer P7443R, Pioneer P7213R, Pioneer P7535R
      (Pioneer Hi-Bred International Inc., Johnston, IA), Hyland Baxxos RR, Hyland
      SR22, and Hyland SR06 (Hyland Seeds, Blenheim, ON, Canada)] using Fourier
      transform infrared attenuated total reflectance (FT/IR-ATR) molecular
      spectroscopy, and to determine the nutrient profile and supply that each variety
      provided for dairy cattle. The protein molecular structure studies showed that
      the amide I to amide II ratio ranged from 1.09 to 1.66 and that the alpha-helix
      to beta-sheet ratio ranged from 0.95 to 1.01 among the new cool-season corn
      varieties. Energy content was significantly different among the new varieties. We
      found significant differences in the protein and carbohydrate subfractions and in
      the ruminal degradation kinetics of the organic matter, crude protein, starch,
      and neutral detergent fiber of the new varieties. The new varieties had similar
      estimated intestinal digestibilities for rumen undegraded crude protein. However,
      the new varieties had significant differences in predicted total truly absorbable
      protein, ranging from 39 to 57 g/kg of dry matter, indicating that these newly
      developed varieties are satisfactory sources of truly absorbed protein for dairy
      cattle. Further study on the molecular structure profiles of cool-season corn in
      relation to its nutrient utilization and availability in dairy cattle is
      necessary.

PMID- 23958022
TI  - Associations between decreased fertility and management factors, claw health, and
      somatic cell count in Swedish dairy cows.
AB  - The aim of this retrospective single-cohort study was to investigate if a rapid
      change in feeding, management, or housing or an increasing incidence of claw
      diseases or udder health problems is associated with decreased reproductive
      performance. Data on individual cows and herds were retrieved from the Swedish
      official milk recording system and questionnaire data on feeding system was
      obtained from the regional dairy associations. In total, 63,561 cows in 759 herds
      were included in the study. The associations between the probability of pregnancy
      at first insemination and number of inseminations per animal submitted for
      artificial insemination and potential predictor variables were investigated using
      a logistic regression model and a Poisson regression model, respectively. The
      results indicated that cows with severe claw lesions or an increasing somatic
      cell count after calving had a lower probability of pregnancy at first
      insemination and had a higher number of inseminations per animal submitted for
      artificial insemination than healthy cows. Variables representing a change in
      housing, production system, or milking system within the period from 6 mo before
      calving until establishment of a new pregnancy were significantly associated with
      decreased reproductive performance. No differences in fertility were observed
      between cows milked in an automatic milking system compared with cows milked
      conventionally. The results indicate that a change of system, rather than the
      actual type of milking or housing system negatively affects reproductive
      performance. Special attention should therefore be paid to the fertility of cows
      when the herd management is changing. It is also important to prevent claw
      lesions and increasing cell counts after calving to avoid a decrease in
      reproductive performance.

PMID- 23958023
TI  - Effect of supplementation with fish oil or microalgae on fatty acid composition
      of milk from cows managed in confinement or pasture systems.
AB  - The objective of this study was to examine the interaction between lipid
      supplement (LS) and management system (MS) on fatty acid (FA) composition of milk
      that could affect its healthfulness as a human food. Forty-eight prepartal
      Holstein cows were blocked by parity and predicted calving date and deployed
      across pasture (PAS; n=23) or confinement (CONF; n=25) systems. Cows within each
      system were assigned randomly to a control (no marine oil supplement) or to 1 of
      2 isolipidic (200 g/d) marine oil supplements: fish oil (FO) or microalgae (MA)
      for 125 +/- 5 d starting 30 d precalving. The experiment was conducted as a split
      plot design, with MS being the whole-plot treatment and LS as the subplot
      treatment. Cows were housed in a tie-stall barn from -30 until 28 +/- 10 d in
      milk (DIM) and were fed total mixed rations with similar formulations. The PAS
      group was then adapted to pasture and rotationally grazed on a perennial sward
      until the end of the experiment (95 +/- 5 DIM). Milk samples were collected at 60
      and 90 DIM for major components and FA analyses. Milk yield (kg/d) was lower in
      PAS (34.0) compared with CONF (40.1) cows. Milk fat percentage was reduced with
      MA compared with FO (3.00 vs. 3.40) and the control (3.56) cows. However, milk
      fat yield (kg/d) was not affected by lipid supplements. Compared with CONF, PAS
      cows produced milk fat with a lower content of 12:0 (-38%), 14:0 (-28%), and 16:0
      (-17%), and more cis-9 18:1 (+32%), 18:3 n-3 (+30%), conjugated linoleic acid
      (CLA; +70%) and trans 18:1 (+34%). Both supplements, regardless of MS, reduced
      similarly the milk fat content of 16:0 (-12%) and increased CLA (+28%) and n-3
      long-chain polyunsaturated FA (n-3 LC-PUFA; +150%). Milk fat content of trans
      18:1 (trans-6 to trans-16) was increased with FO or MA, although the effect was
      greater with MA (+81%) than with FO (+42%). The interaction between MS and LS was
      significant only for trans-11 18:1 (vaccenic acid, VA) and cis-9,trans-11 CLA
      (rumenic acid). In contrast to CONF, feeding FO or MA to PAS cows did not
      increase milk fat content of VA and rumenic acid. We concluded that compared with
      CONF, milk from PAS cows had a more healthful FA composition. Feeding either FO
      or MA improved n-3 long-chain polyunsaturated FA and reduced levels of 16:0 in
      milk fat, regardless of MS, but concurrently increased the trans 18:1 isomers
      other than VA, at the expense of VA, particularly in grazing cows.

PMID- 23958024
TI  - Resistance of the constitutive microflora of biofilms formed on whey reverse
      osmosis membranes to individual cleaning steps of a typical clean-in-place
      protocol.
AB  - This experiment evaluates the effectiveness of individual steps of a clean-in
      place protocol against the biofilm constitutive microflora isolated from the
      biofilms developed on whey reverse-osmosis membranes, aged 2 to 14 mo, under
      industrial processing conditions. The isolates used for the in vitro resistance
      studies included species of Bacillus, Enterococcus, Streptococcus,
      Staphylococcus, Micrococcus, Aeromonas, Corynebacterium, Pseudomonas, Klebsiella,
      and Escherichia. The 6 cleaning steps (alkali, surfactant, acid, enzyme, a second
      surfactant, and sanitizer treatment) revealed resistance of isolates in both
      planktonic and biofilm-embedded cell states. The most effective step was the acid
      treatment, which resulted in 4.54 to 7.90 and 2.09 to 5.02 log reductions of the
      planktonic and biofilm-embedded cells, respectively. Although the sanitizer step
      causing a reduction of 4.91 to 8.33 log in the case of planktonic cells, it was
      less effective against the biofilm-embedded cells, resulting in a reduction of
      0.59 to 1.64 log. Bacillus spp. showed the highest resistance in both planktonic,
      as well as embedded cell states.

PMID- 23958025
TI  - Randomized noninferiority clinical trial evaluating 3 commercial dry cow mastitis
      preparations: II. Cow health and performance in early lactation.
AB  - The objective of this randomized noninferiority clinical trial was to compare the
      effect of treatment with 3 different dry cow therapy formulations at dry-off on
      cow-level health and production parameters in the first 100 d in milk (DIM) in
      the subsequent lactation, including 305-d mature-equivalent (305 ME) milk
      production, linear score (LS), risk for the cow experiencing a clinical mastitis
      event, risk for culling or death, and risk for pregnancy by 100 DIM. A total of
      1,091 cows from 6 commercial dairy herds in 4 states (California, Iowa,
      Minnesota, and Wisconsin) were randomly assigned at dry-off to receive treatment
      with 1 of 3 commercial products: Quartermaster (QT; Zoetis Animal Health,
      Madison, NJ), Spectramast DC (SP; Zoetis Animal Health) or ToMorrow Dry Cow (TM;
      Boehringer Ingelheim Vetmedica Inc., St Joseph, MO). All clinical mastitis,
      pregnancy, culling, and death events occurring in the first 100 DIM were recorded
      by farm staff using an on-farm electronic record-keeping system. Dairy Herd
      Improvement Association test-day records of milk production and milk component
      testing were retrieved electronically. Mixed linear regression analysis was used
      to describe the effect of treatment on 305ME milk production and LS recorded on
      the last Dairy Herd Improvement Association test day before 100 DIM. Cox
      proportional hazards regression analysis was used to describe the effect of
      treatment on risk for experiencing a case of clinical mastitis, risk for leaving
      the herd, and risk for pregnancy between calving and 100 DIM. Results showed no
      effect of treatment on adjusted mean 305 ME milk production (QT=11,759 kg,
      SP=11,574 kg, and TM=11,761 kg) or adjusted mean LS (QT=1.8, SP=1.9, and TM=1.6)
      on the last test day before 100 DIM. Similarly, no effect of treatment was
      observed on risk for a clinical mastitis event (QT=14.8%, SP=12.7%, and
      TM=15.0%), risk for leaving the herd (QT=7.5%, SP=9.2%, and TM=10.3%), or risk
      for pregnancy (QT=31.5%, SP=26.1%, and TM=26.9%) between calving and 100 DIM.

PMID- 23958027
TI  - Carrier-free functionalized multidrug nanorods for synergistic cancer therapy.
AB  - We developed carrier-free multidrug nanocrystals (MDNCs) for the combination
      chemotherapy with synergistic effect, improved tolerance and imaging capability
      for cancer treatment. Three widely used hydrophobic drugs, methotrexate (MTX), 10
      hydroxycamptothecin (HCPT) and paclitaxel (PTX), were prepared into one nanorod,
      and then conjugated with poly(ethylene glycol) (PEG) to improve their water
      dispersity and bio-environmental stability. It should be noted that only trace
      amount of PEG was used for surface modification, which ensures a high drug
      loading capacity of the resulting PEGylated MDNCs. In vitro studies showed that
      the MDNCs revealed an obviously higher cytotoxicity than individual drugs in the
      same dose and suppressed drug resistance against PTX resistant MCF-7/ADR cancer
      cells, indicating its synergistic effect and improved tolerance. After in vivo
      intravenous injection, the MDNCs exhibits a synergetic in vivo therapeutic effect
      and possesses obviously superior antitumor effect compared to free multidrugs
      treatment group and individual drug treatment groups, and no statistically
      significant weight loss was observed. The MDNCs can also gain imaging
      capabilities by encapsulated with an organic dye, which render the multidrug
      nanorod an all-in-one processing system for cancer diagnosis and treatment. 

PMID- 23958028
TI  - Toward in vivo detection of hydrogen peroxide with ultrasound molecular imaging.
AB  - We present a new class of ultrasound molecular imaging agents that extend upon
      the design of micromotors that are designed to move through fluids by catalyzing
      hydrogen peroxide (H2O2) and propelling forward by escaping oxygen microbubbles.
      Micromotor converters require 62 mm of H2O2 to move - 1000-fold higher than is
      expected in vivo. Here, we aim to prove that ultrasound can detect the expelled
      microbubbles, to determine the minimum H2O2 concentration needed for microbubble
      detection, explore alternate designs to detect the H2O2 produced by activated
      neutrophils and perform preliminary in vivo testing. Oxygen microbubbles were
      detected by ultrasound at 2.5 mm H2O2. Best results were achieved with a 400-500
      nm spherical design with alternating surface coatings of catalase and PSS over a
      silica core. The lowest detection limit of 10-100 MUm was achieved when assays
      were done in plasma. Using this design, we detected the H2O2 produced by freshly
      isolated PMA-activated neutrophils allowing their distinction from naive
      neutrophils. Finally, we were also able to show that direct injection of these
      nanospheres into an abscess in vivo enhanced ultrasound signal only when they
      contained catalase, and only when injected into an abscess, likely because of the
      elevated levels of H2O2 produced by inflammatory mediators.

PMID- 23958030
TI  - Interarterial course of coronary artery anomaly presenting as Brugada-like ECG
      and aborted cardiac death-Multidisciplinary images facilitate the diagnosis.

PMID- 23958029
TI  - The effect of mesenchymal stem cells delivered via hydrogel-based tissue
      engineered periosteum on bone allograft healing.
AB  - Allografts remain the clinical "gold standard" for treatment of critical sized
      bone defects despite minimal engraftment and ~60% long-term failure rates.
      Therefore, the development of strategies to improve allograft healing and
      integration are necessary. The periosteum and its associated stem cell
      population, which are lacking in allografts, coordinate autograft healing. Herein
      we utilized hydrolytically degradable hydrogels to transplant and localize
      mesenchymal stem cells (MSCs) to allograft surfaces, creating a periosteum
      mimetic, termed a 'tissue engineered periosteum'. Our results demonstrated that
      this tissue engineering approach resulted in increased graft vascularization
      (~2.4-fold), endochondral bone formation (~2.8-fold), and biomechanical strength
      (1.8-fold), as compared to untreated allografts, over 16 weeks of healing.
      Despite this enhancement in healing, the process of endochondral ossification was
      delayed compared to autografts, requiring further modifications for this approach
      to be clinically acceptable. However, this bottom-up biomaterials approach, the
      engineered periosteum, can be augmented with alternative cell types, matrix cues,
      growth factors, and/or other small molecule drugs to expedite the process of
      ossification. 

PMID- 23958031
TI  - Mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated
      progeny express chemokine receptor CCR9 and chemotactically migrate toward CCL25
      or serum.
AB  - INTRODUCTION: Guided migration of chondrogenically differentiated cells has not
      been well studied, even though it may be critical for growth, repair, and
      regenerative processes. The chemokine CCL25 is believed to play a critical role
      in the directional migration of leukocytes and stem cells. To investigate the
      motility effect of serum- or CCL25-mediated chemotaxis on chondrogenically
      differentiated cells, mesenchymal stem cells (MSCs) were induced to chondrogenic
      lineage cells. METHODS: MSC-derived chondrogenically differentiated cells were
      characterized for morphology, histology, immunohistochemistry, quantitative
      polymerase chain reaction (qPCR), surface profile, and serum- or CCL25-mediated
      cell migration. Additionally, the chemokine receptor, CCR9, was examined in
      different states of MSCs. RESULTS: The chondrogenic differentiated state of MSCs
      was positive for collagen type II and Alcian blue staining, and showed
      significantly upregulated expression of COL2A1and SOX9, and downregulated
      expression of CD44, CD73, CD90, CD105 and CD166, in contrast to the
      undifferentiated and dedifferentiated states of MSCs. For the chondrogenic
      differentiated, undifferentiated, and dedifferentiated states of MSCs, the serum
      mediated chemotaxis was in a percentage ratio of 33%:84%:85%, and CCL25-mediated
      chemotaxis was in percentage ratio of 12%:14%:13%, respectively. On the protein
      level, CCR9, receptor of CCL25, was expressed in the form of extracellular and
      intracellular domains. On the gene level, qPCR confirmed the expression of CCR9
      in different states of MSCs. CONCLUSIONS: CCL25 is an effective cue to guide
      migration in a directional way. In CCL25-mediated chemotaxis, the cell-migration
      rate was almost the same for different states of MSCs. In serum-mediated
      chemotaxis, the cell-migration rate of chondrogenically differentiated cells was
      significantly lower than that in undifferentiated or dedifferentiated cells.
      Current knowledge of the surface CD profile and cell migration could be
      beneficial for regenerative cellular therapies.

PMID- 23958032
TI  - Understanding adaptive gait in lower-limb amputees: insights from multivariate
      analyses.
AB  - BACKGROUND: In this paper we use multivariate statistical techniques to gain
      insights into how adaptive gait involving obstacle crossing is regulated in lower
      limb amputees compared to able-bodied controls, with the aim of identifying
      underlying characteristics that differ between the two groups and consequently
      highlighting gait deficits in the amputees. METHODS: Eight unilateral trans
      tibial amputees and twelve able-bodied controls completed adaptive gait trials
      involving negotiating various height obstacles; with amputees leading with their
      prosthetic limb. Spatiotemporal variables that are regularly used to quantify how
      gait is adapted when crossing obstacles were determined and subsequently analysed
      using multivariate statistical techniques. RESULTS AND DISCUSSION: There were
      fundamental differences in the adaptive gait between the two groups. Compared to
      controls, amputees had a reduced approach velocity, reduced foot placement
      distance before and after the obstacle and reduced foot clearance over it, and
      reduced lead-limb knee flexion during the step following crossing. Logistic
      regression analysis highlighted the variables that best distinguished between the
      gait of the two groups and multiple regression analysis (with approach velocity
      as a controlling factor) helped identify what gait adaptations were driving the
      differences seen in these variables. Getting closer to the obstacle before
      crossing it appeared to be a strategy to ensure the heel of the lead-limb foot
      passed over the obstacle prior to the foot being lowered to the ground. Despite
      adopting such a heel clearance strategy, the lead-foot was positioned closer to
      the obstacle following crossing, which was likely a result of a desire to attain
      a limb/foot angle and orientation at instant of landing that minimised loads on
      the residuum (as evidenced by the reduced lead-limb knee flexion during the step
      following crossing). These changes in foot placement meant the foot was in a
      different part of swing at point of crossing and this explains why foot clearance
      was considerably reduced in amputees. CONCLUSIONS: These results highlight that
      trans-tibial amputees use quite different gait adaptations to cross obstacles
      compared with controls (at least when leading with their prosthetic limb),
      indicating they are governed by different constraints; seemingly related to how
      they land on/load their prosthesis after crossing the obstacle.

PMID- 23958033
TI  - Assessment of postoperative pain after unilateral mastectomy using two different
      surgical techniques in dogs.
AB  - BACKGROUND: There are few studies reporting pain and postoperative analgesia
      associated with mastectomy in dogs. The aim of this study was to evaluate
      postoperative pain after unilateral mastectomy using two different surgical
      techniques in the dog. FINDINGS: Twenty female dogs were assigned (n=10/group) to
      undergo unilateral mastectomy using either the combination of sharp and blunt
      dissection (SBD) or the modified SBD (mSBD) technique, in which the mammary chain
      is separated from the abdominal wall entirely by blunt (hand and finger)
      dissection except for a small area cranial to the first gland, in a prospective,
      randomized, clinical trial. All dogs were premedicated with intramuscular
      acepromazine (0.05 mg/kg) and morphine (0.3 mg/kg). Anesthesia was induced with
      intravenous ketamine (5 mg/kg) and diazepam (0.25 mg/kg), and maintained with
      isoflurane. Subcutaneous meloxicam (0.2 mg/kg) was administered before surgery.
      Postoperative pain was evaluated according to the University of Melbourne pain
      scale (UMPS) by an observer who was blinded to the surgical technique.. Rescue
      analgesia was provided by the administration of intramuscular morphine (0.5
      mg/kg) if pain scores were >14 according to the UMPS. Data were analyzed using t
      tests and ANOVA (P>0.05). There were no significant differences between the
      groups for age, weight, extubation time, and duration of surgery and anesthesia
      (P>0.05). There were no significant differences for postoperative pain scores
      between groups. Rescue analgesia was required in one dog in each group.
      CONCLUSIONS: The two surgical techniques produced similar surgical times,
      incidence of perioperative complications and postoperative pain. Multimodal
      analgesia is recommended for treatment of postoperative pain in dogs undergoing
      unilateral mastectomy.

PMID- 23958034
TI  - The role of monocytes in the development of Tuberculosis-associated Immune
      Reconstitution Inflammatory Syndrome.
AB  - BACKGROUND: Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome
      (TB-IRIS) is a common complication of combined antiretroviral therapy (cART) in
      HIV-TB co-infected patients. However, the disease mechanism is poorly understood,
      prognosis of TB-IRIS is currently impossible, and diagnosis is highly
      challenging. We analyzed whether the gene expression of monocytes could be
      correlated with TB-IRIS pathogenesis and could be used to classify patients
      predisposed to TB-IRIS. METHODS: Monocyte gene expression was compared between
      patients who developed TB-IRIS and matched controls. We carried out whole-genome
      expression profiling using Affymetrix GeneChip((r)) ST 1.1 arrays at two time
      points: before cART initiation (baseline) and at week two post-cART initiation.
      For each time-point, we used different statistical approaches to identify
      molecular signatures which could be used as classifiers. We also functionally
      mapped the modulated cellular pathways using the software package Ingenuity
      Pathway Analysis. RESULTS: At baseline, before introduction of cART and before
      onset of symptoms, monocyte gene expression was already perturbed in patients who
      subsequently developed TB-IRIS, indicating a possible involvement of monocytes in
      TB-IRIS predisposition. The differences in monocyte gene expression in TB-IRIS
      patients became even more clear after two weeks of cART (when TB-IRIS commonly
      occurs), with more than 100 genes for which expression showed a fold change
      greater than 1.5. Both at baseline and at week two post-cART initiation, a
      classifier of 8 and 9 genes, respectively could be built, which allowed
      discrimination of TB-IRIS cases and controls. Pathway analyses revealed that the
      majority of the dysregulated genes in TB-IRIS - at the time of the IRIS episode,
      but also already at baseline - are associated with infection and inflammation.
      Relevant biological functions which were perturbed before/during TB-IRIS included
      "Role of Pattern Recognition Receptors in Recognition of Bacteria and Viruses"
      and "Complement System". CONCLUSION: Our results indicate an involvement of
      monocytes in predisposition to/development of TB-IRIS, and suggest a number of
      functional pathways which may play a role in TB-IRIS development. This
      comprehensive study of gene regulation in monocytes provides baseline data for
      further studies into biomarkers for prognosis and diagnosis of TB-IRIS.

PMID- 23958035
TI  - RCT of a promising vocational/employment program for high-risk juvenile
      offenders.
AB  - Juvenile offenders with substance use problems are at high risk for deleterious
      long-term outcomes. This study evaluated the capacity of a promising vocational
      and employment training program in the building sector (i.e., Community
      Restitution Apprenticeship-Focused Training, CRAFT) to mitigate such outcomes
      through enhanced employment and education. Participants were 97 high-risk
      juvenile offenders (mean age=15.8 years) randomized to CRAFT versus education as
      usual (EAU) intervention conditions. Multi-method procedures measured employment,
      education, substance use, mental health, and criminal outcomes through a 30-month
      post-baseline follow-up. CRAFT was significantly more effective than EAU at
      increasing rates of youth employment and GED attendance. Intervention effects
      were not observed, however, for months employed, hours worked, or hourly wage.
      Measures of youth substance use, mental health symptoms, and criminal activity
      showed no favorable or iatrogenic effects. The potential of CRAFT was modestly
      supported, and suggestions were made for future research.

PMID- 23958036
TI  - How the stigma of low literacy can impair patient-professional spoken
      interactions and affect health: insights from a qualitative investigation.
AB  - BACKGROUND: Low literacy is a significant problem across the developed world. A
      considerable body of research has reported associations between low literacy and
      less appropriate access to healthcare services, lower likelihood of self-managing
      health conditions well, and poorer health outcomes. There is a need to explore
      the previously neglected perspectives of people with low literacy to help explain
      how low literacy can lead to poor health, and to consider how to improve the
      ability of health services to meet their needs. METHODS: Two stage qualitative
      study. In-depth individual interviews followed by focus groups to confirm
      analysis and develop suggestions for service improvements. A purposive sample of
      29 adults with English as their first language who had sought help with literacy
      was recruited from an Adult Learning Centre in the UK. RESULTS: Over and above
      the well-documented difficulties that people with low literacy can have with the
      written information and complex explanations and instructions they encounter as
      they use health services, the stigma of low literacy had significant negative
      implications for participants' spoken interactions with healthcare
      professionals.Participants described various difficulties in consultations, some
      of which had impacted negatively on their broader healthcare experiences and
      abilities to self-manage health conditions. Some communication difficulties were
      apparently perpetuated or exacerbated because participants limited their
      conversational engagement and used a variety of strategies to cover up their low
      literacy that could send misleading signals to health professionals.
      Participants' biographical narratives revealed that the ways in which they
      managed their low literacy in healthcare settings, as in other social contexts,
      stemmed from highly negative experiences with literacy-related stigma, usually
      from their schooldays onwards. They also suggest that literacy-related stigma can
      significantly undermine mental wellbeing by prompting self-exclusion from social
      participation and generating a persistent anxiety about revealing literacy
      difficulties. CONCLUSION: Low-literacy-related stigma can seriously impair
      people's spoken interactions with health professionals and their potential to
      benefit from health services. As policies increasingly emphasise the need for
      patients' participation, services need to simplify the literacy requirements of
      service use and health professionals need to offer non-judgemental (universal)
      literacy-sensitive support to promote positive healthcare experiences and
      outcomes.

PMID- 23958037
TI  - Joint symbolic analyses of heart rate, blood pressure, and respiratory dynamics.
AB  - INTRODUCTION: The dynamics of cardiovascular variables are modulated by
      respiration. The aim of this study was to assess baroreflex function in normal
      subjects based on the joint symbolic dynamics of heart rate, blood pressure and
      respiration. METHODS: ECG, continuous blood pressure and respiration were
      recorded in ten healthy subjects during rest in the supine position and upon
      standing. Beat-to-beat time series of heart rate, systolic blood pressure and
      respiratory phase were extracted and transformed into binary symbol sequences.
      Words of length two that were reflective of baroreflex activity were
      statistically analysed with respect to the respiratory phase. RESULTS: Symbolic
      analysis showed a significant influence of the respiratory phase on the
      occurrence of baroreflex patterns. Upon standing, the frequency of baroreflex
      words increased and the effect of respiration appeared to be reduced.
      CONCLUSIONS: Symbolic dynamics provide a simple representation of cardiovascular
      dynamics and may be useful for assessing baroreflex function.

PMID- 23958047
TI  - Incidence of pulmonary cement embolism after real-time CT fluoroscopy-guided
      vertebroplasty.
AB  - PURPOSE: To prospectively evaluate the incidence of pulmonary cement embolism
      (PCE) after vertebroplasty in procedures performed under real-time computed
      tomographic (CT) fluoroscopy guidance. MATERIALS AND METHODS: A total of 85
      vertebroplasties were performed in 51 consecutive patients (31 women, 20 men;
      mean age, 71.9 y; range, 48-92 y) in 51 sessions. The needle was inserted with
      guidance from intermittent single-shot CT scans, and intermittent CT fluoroscopy
      was used during cement injection only. To reduce the risk of extravertebral or
      extraosseous leakage, several procedures (cement injection stopping/slowing,
      needle position changes) were employed. The chest and treated bone were scanned
      immediately after vertebroplasty. These CT images included the entire thorax as
      well as the treated vertebrae. RESULTS: No cement emboli were observed on CT
      after vertebroplasty. After 85 vertebroplasty procedures, 44 extravertebral leaks
      were detected. Epidural leaks were observed on CT in six treated vertebrae (7%),
      in 12 cases in the anterior external venous plexus (14.1%), in five in the azygos
      vein (5.8%), in 19 in the disc space (22%), and in two in the foraminal space
      (2.3%). On a per-patient basis, the odds of leaks increased with the number of
      vertebroplasties (P = .05) and the volume of cement used (P = .0412). There was
      also a higher probability of leak (P < .05) for osteoporotic vertebral
      compression fractures (67.9%; 95% confidence interval, 47.7%-84.1%) than
      osteolytic spinal metastases (34.8%; 16.4%-57.3%). CONCLUSIONS: PCE did not occur
      after vertebroplasty under CT fluoroscopy guidance. Further larger prospective
      vertebroplasty studies are needed to compare the rates of PCE for CT versus
      conventional fluoroscopic guidance.

PMID- 23958048
TI  - Mixed epithelial and stromal tumor of the kidney: report of eight cases and
      literature review.
AB  - Mixed epithelial and stromal tumor of the kidney (MESTK) is the term given to a
      class of uncommon biphasic tumors of the kidney, with few reported cases. We
      describe eight cases of MESTK with detailed clinicopathological data and follow
      up information. With this report, we hope to increase clinical awareness that
      MESTK should be considered as one of the possible diagnoses for cystic renal
      mass, especially in peri-menopausal women or those who receive hormone therapy.
      In addition, regular follow-up is necessary for the any cases with malignant
      potential. 

PMID- 23958049
TI  - Respiratory tract rather than cutaneous atopic allergy inversely associate with
      multiple sclerosis: a case-control study.
AB  - BACKGROUND: It has been previously shown that genetic or environmental factors,
      which promote susceptibility to allergic conditions, prevent the development of
      Th1-mediated inflammatory disease of multiple sclerosis (MS). To investigate the
      prediction value of lifetime atopic allergy in development of the future MS, a
      case-control study was designed. METHODS: Cases and controls were interviewed
      between December 2007 and April 2008 and they were asked if they had symptoms or
      diagnosis of allergies (including respiratory tract allergy, RTA; coetaneous
      allergy, CA; food/drug allergy, FDA) before MS diagnosis. RESULTS: Of 390
      participants (195 controls and 195 cases), 125 healthy controls (64.1%) and 105
      cases (53.8%) reported history of at least one type of atopic allergy (P=0.04). A
      positive history of RTA (OR 0.43; 95% CI 0.28-0.66) or FDA (OR 0.24; 95% CI 0.13
      0.43) was inversely associated with the risk of MS. No statistically significant
      association was found between the history of CA and MS. CONCLUSIONS: There is a
      significant inverse association between RTA and MS that is compatible with a
      Th1/Th2 imbalance. History of RTA can be considered as a clinically useful risk
      reducing factor of MS.

PMID- 23958050
TI  - Peripheral vascular disease as remote ischemic preconditioning, for acute stroke.
AB  - OBJECTIVES: Remote ischemic preconditioning (RIPC) is a powerful endogenous
      mechanism whereby a brief period of ischemia is capable of protecting remote
      tissues from subsequent ischemic insult. While this phenomenon has been
      extensively studied in the heart and brain in animal models, little work has been
      done to explore the effects of RIPC in human patients with acute cerebral
      ischemia. This study investigates whether chronic peripheral hypoperfusion, in
      the form of pre-existing arterial peripheral vascular disease (PVD) that has not
      been surgically treated, is capable of inducing neuroprotective effects for acute
      ischemic stroke. METHODS: Individuals with PVD who had not undergone prior
      surgical treatment were identified from a registry of stroke patients. A control
      group within the same database was identified by matching patient's demographics
      and risk factors. The two groups were compared in terms of outcome by NIH Stroke
      Scale (NIHSS), modified Rankin scale (mRS), mortality, and volume of infarcted
      tissue at presentation and at discharge. RESULTS: The matching algorithm
      identified 26 pairs of PVD-control patients (9 pairs were female and 17 pairs
      were male). Age range was 20-93 years (mean 73). The PVD group was found to have
      significantly lower NIHSS scores at admission (NIHSS<=4: PVD 47.1%, control
      4.35%, p<0.003), significantly more favorable outcomes at discharge (mRS<=2: PVD
      30.8%, control 3.84%, p<0.012), and a significantly lower mortality rate (PVD
      26.9%, control 57.7%, p=0.024). Mean acute stroke volume at admission and at
      discharge were significantly lower for the PVD group (admission: PVD 39.6 mL,
      control 148.3 mL, p<0.005 and discharge: PVD 111.7 mL, control 275 mL, p<0.001).
      CONCLUSION: Chronic limb hypoperfusion induced by PVD can potentially produce a
      neuroprotective effect in acute ischemic stroke. This effect resembles the
      neuroprotection induced by RIPC in preclinical models.

PMID- 23958051
TI  - Ruptured middle cerebellar peduncle AVM presenting with a coma treated to
      complete recovery with endovascular and intensive care therapy: discussion of
      management.

PMID- 23958052
TI  - Residual rates of mortality in patients with severe sepsis: a fatality or a new
      challenge?
AB  - Phase III clinical trials on severe sepsis and septic shock published during the
      past decade have failed to reveal the superiority of any therapeutic intervention
      on mortality compared with evolving standards of care, with the exception of the
      Early-Goal Directed Therapy reported in 2001. This viewpoint paper presents an
      analysis of these studies in order to understand what lessons can be learned and
      proposes perspectives for future study designs. A total of 102 studies were
      selected among clinical trials published in the field of severe sepsis and septic
      shock from 2001 to 2013, based on the assessment of a therapeutic intervention
      and mortality as an outcome. Studies were further selected according to
      randomized, controlled trial (RCT) quality criteria and analysed according to
      reported data. Most (n = 61) were excluded because they did not comply with RCT
      quality criteria or did not report inclusion criteria or patient severity (n =
      22). The 19 remaining studies were categorized into three groups depending on
      whether the intervention assessed led to better, worse, or equivalent outcomes.
      It appears that the mortality rate in the control arm, ranging from 17% to 61%,
      impacted the results, with a benefit reported in the studies with the highest
      rates. Both heterogeneous studied populations and uncontrolled diversity of care
      among participating centres probably contributed to discrepancies between studies
      assessing the same intervention. The new challenge to enhance the probability of
      decreasing mortality rates should include a more appropriate definition of sepsis
      based on more specific criteria involving biomarker use and accurate patient
      phenotypes. 

PMID- 23958053
TI  - Radical cystectomy for bladder cancer: oncologic outcome in 271 Chinese patients.
AB  - Few large scale studies have reported the oncologic outcome of radical cystectomy
      for treating bladder cancer in China; hence, we lack long-term prognostic
      information. The aim of the current study was to determine the survival rate and
      prognostic factors of patients who underwent radical cystectomy for bladder
      cancer in a Chinese medical center. We retrospectively analyzed clinicopathologic
      data from 271 bladder cancer patients who underwent radical cystectomy between
      2000 and 2011. Univariate and multivariate analyses were conducted to identify
      independent prognostic predictors for this cohort. Median follow-up was 31.7
      months (range, 0.2-139.1 months). Thirty-day mortality was (1.4%). The 5-year
      recurrence-free survival, cancer-specific survival (CSS), and overall survival
      rates were 61.6%, 72.9%, and 68.0%, respectively. The 5-year CSS rates of
      patients with T1-T4 disease were 90.7%, 85.0%, 51.0%, and 18.0%, respectively.
      Patients with organ-confined disease had a higher 5-year CSS rate than those with
      extravesical disease (81.4% vs. 34.9%, P < 0.001). For the 38 patients (14%) with
      lymph node involvement, the 5-year CSS rate was 27.7%-significantly lower than
      that of patients without lymph node metastasis (P < 0.001). The 5-year CSS rate
      was much higher in patients with low grade tumor than in those with high grade
      tumor (98.1% vs. 68.1%, P < 0.001). Multivariate Cox regression showed that
      patient age (hazard ratio, 2.045; P = 0.013) and T category (hazard ratio, 2.213;
      P < 0.001) were independent predictors for CSS. These results suggest that
      radical cystectomy is a safe and effective method for treating bladder cancer in
      Chinese patients. Old age and high T category were associated with poor prognosis
      in bladder cancer patients who underwent radical cystectomy. 

PMID- 23958054
TI  - Pancreatic pseudocyst or a cystic tumor of the pancreas?
AB  - Pancreatic pseudocysts are the most common cystic lesions of the pancreas and may
      complicate acute pancreatitis, chronic pancreatitis, or pancreatic trauma. While
      the majority of acute pseudocysts resolve spontaneously, few may require
      drainage. On the other hand, pancreatic cystic tumors, which usually require
      extirpation, may disguise as pseudocysts. Hence, the distinction between the two
      entities is crucial for a successful outcome. We conducted this study to
      highlight the fundamental differences between pancreatic pseudocysts and cystic
      tumors so that relevant management plans can be devised. We reviewed the data of
      patients with pancreatic cystic lesions that underwent intervention between June
      2007 and December 2010 in our hospital. We identified 9 patients (5 males and 4
      females) with a median age of 40 years (range, 30-70 years). Five patients had
      pseudocysts, 2 had cystic tumors, and 2 had diseases of undetermined pathology.
      Pancreatic pseudocysts were treated by pseudocystogastrostomy in 2 cases and
      percutaneous drainage in 3 cases. One case recurred after percutaneous drainage
      and required pseudocystogastrostomy. The true pancreatic cysts were serous
      cystadenoma, which was treated by distal pancreatectomy, and mucinous
      cystadenocarcinoma, which was initially treated by drainage, like a pseudocyst,
      and then by distal pancreatectomy when its true nature was revealed. We conclude
      that every effort should be exerted to distinguish between pancreatic pseudocysts
      and cystic tumors of the pancreas to avoid the serious misjudgement of draining
      rather than extirpating a pancreatic cystic tumor. Additionally, percutaneous
      drainage of a pancreatic pseudocyst is a useful adjunct that may substitute for
      surgical drainage. 

PMID- 23958056
TI  - An early history of human breast cancer: West meets East.
AB  - Cancer has been increasingly recognized as a global issue. This is especially
      true in countries like China, where cancer incidence has increased likely because
      of changes in environment and lifestyle. However, cancer is not a modern disease;
      early cases have been recorded in ancient medical books in the West and in China.
      Here, we provide a brief history of cancer, focusing on cancer of the breast, and
      review the etymology of ai, the Chinese character for cancer. Notable findings
      from both Western and Chinese traditional medicine are presented to give an
      overview of the most important, early contributors to our evolving understanding
      of human breast cancer. We also discuss the earliest historical documents to
      record patients with breast cancer. 

PMID- 23958055
TI  - Enhanced MGMT expression contributes to temozolomide resistance in glioma stem
      like cells.
AB  - O6-methylguanine DNA methyltransferase (MGMT) can remove DNA alkylation adducts,
      thereby repairing damaged DNA and contributing to the drug resistance of gliomas
      to alkylating agents. In addition, glioma stem-like cells (GSCs) have been
      demonstrated to be involved in the recurrence and treatment resistance of
      gliomas. In this study, we aimed to investigate MGMT expression and regulatory
      mechanisms in GSCs and the association of MGMT with temozolomide (TMZ)
      sensitivity. GSCs were enriched from one MGMT-positive cell line (SF-767) and 7
      MGMT-negative cell lines (U251, SKMG-4, SKMG-1, SF295, U87, MGR1, and MGR2)
      through serum-free clone culture. GSCs from the U251G, SKMG-4G, SF295G, and SKMG
      1G cell lines became MGMT-positive, but those from the U87G, MGR1G, and MGR2G
      cell lines remained MGMT-negative. However, all the GSCs and their parental
      glioma cell lines were positive for nuclear factor-kappaB (NF-kappaB). In
      addition, GSCs were more resistant to TMZ than their parental glioma cell lines
      (P < 0.05). However, there was no significant difference in the 50% inhibition
      concentration (IC50) of TMZ between MGMT-positive and MGMT-negative GSCs (P >
      0.05). When we treated the MGMT-positive GSCs with TMZ plus MG-132 (an NF-kappaB
      inhibitor), the antitumor activity was significantly enhanced compared to that of
      GSCs treated with TMZ alone (P <0.05). Furthermore, we found that MGMT expression
      decreased through the down-regulation of NF-kappaB expression by MG-132. Our
      results show that MG-132 may inhibit NF-kappaB expression and further decrease
      MGMT expression, resulting in a synergistic effect on MGMT-positive GSCs. These
      results indicate that enhanced MGMT expression contributes to TMZ resistance in
      MGMT-positive GSCs. 

PMID- 23958057
TI  - High plasma fibrinogen concentration and platelet count unfavorably impact
      survival in non-small cell lung cancer patients with brain metastases.
AB  - High expression of fibrinogen and platelets are often observed in non-small cell
      lung cancer (NSCLC) patients with local regional or distant metastasis. However,
      the role of these factors remains unclear. The aims of this study were to
      evaluate the prognostic significance of plasma fibrinogen concentration and
      platelet count, as well as to determine the overall survival of NSCLC patients
      with brain metastases. A total of 275 NSCLC patients with brain metastasis were
      enrolled into this study. Univariate analysis showed that high plasma fibrinogen
      concentration was associated with age>=65 years (P = 0.011), smoking status (P =
      0.009), intracranial symptoms (P = 0.022), clinical T category (P = 0.010),
      clinical N category (P = 0.003), increased partial thromboplastin time (P <
      0.001), and platelet count (P < 0.001). Patients with low plasma fibrinogen
      concentration demonstrated longer overall survival compared with those with high
      plasma fibrinogen concentration (median, 17.3 months versus 11.1 months;
      P<=0.001). A similar result was observed for platelet counts (median, 16.3 months
      versus 11.4 months; P = 0.004). Multivariate analysis showed that both plasma
      fibrinogen concentration and platelet count were independent prognostic factors
      for NSCLC with brain metastases (R2 = 1.698, P < 0.001 and R2 = 1.699, P < 0.001,
      respectively). Our results suggest that high plasma fibrinogen concentration and
      platelet count indicate poor prognosis for NSCLC patients with brain metastases.
      Thus, these two biomarkers might be independent prognostic predictors for this
      subgroup of NSCLC patients.

PMID- 23958058
TI  - Preliminary assessment of nasopharyngeal carcinoma incidence in the Philippines:
      a second look at published data from four centers.
AB  - In endemic regions such as southern China and Southeast Asia, the annual
      incidence of nasopharyngeal carcinoma (NPC) ranges from 3 to 30 per 100,000. In
      the Philippines, the estimated incidence in 2010 was 1.2 per 100,000. However,
      this rate is based on data collected from registries covering only two regions in
      the country. Here, we report the findings from our study to better approximate
      the incidence of NPC in the Philippines. Between September 1, 2011 and August 31,
      2012, data were collected from 49 patients from 4 different institutions
      University of Santo Tomas, Makati Medical Center, Philippine Oncology Center
      Corporation, and Cardinal Santos Memorial Medical Center-using a NPC screening
      questionnaire. Crude incidence was 0.09 per 100,000. Age-standardized incidences
      using Segi and WHO standards were 2.08 and 1.79 per 100,000, respectively. Of the
      49 patients, 31 were males and 18 were females, and 71% of patients were between
      30 and 59 years old. WHO types II and III represented 22% and 78% of the
      subjects, respectively, and 75.5% of cases were locally advanced (stages III
      IVB). Although the age-standardized incidence from the 4 institutions was
      numerically higher than the published age-standardized incidence (2.07 per
      100,000 vs. 1.2 per 100,000), two-proportion z-test showed no significant
      difference between them (P = 0.68). A more concerted effort is needed for a
      better approximation of the country's NPC disease burden. 

PMID- 23958059
TI  - Pharmaceutically active secondary metabolites of marine actinobacteria.
AB  - Marine actinobacteria are one of the most efficient groups of secondary
      metabolite producers and are very important from an industrial point of view.
      Many representatives of the order Actinomycetales are prolific producers of
      thousands of biologically active secondary metabolites. Actinobacteria from
      terrestrial sources have been studied and screened since the 1950s, for many
      important antibiotics, anticancer, antitumor and immunosuppressive agents.
      However, frequent rediscovery of the same compounds from the terrestrial
      actinobacteria has made them less attractive for screening programs in the recent
      years. At the same time, actinobacteria isolated from the marine environment have
      currently received considerable attention due to the structural diversity and
      unique biological activities of their secondary metabolites. They are efficient
      producers of new secondary metabolites that show a range of biological activities
      including antibacterial, antifungal, anticancer, antitumor, cytotoxic,
      cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral,
      antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the
      current status of research on marine actinobacteria yielding pharmaceutically
      active secondary metabolites. Bioactive compounds from marine actinobacteria
      possess distinct chemical structures that may form the basis for synthesis of new
      drugs that could be used to combat resistant pathogens. With the increasing
      advancement in science and technology, there would be a greater demand for new
      bioactive compounds synthesized by actinobacteria from various marine sources in
      future. 

PMID- 23958062
TI  - Characteristics and prognosis analysis of additional chromosome abnormalities in
      newly diagnosed acute promyelocytic leukemia treated with arsenic trioxide as the
      front-line therapy.
AB  - Currently, there are few studies that address the prognostic significance of
      baseline additional chromosomal abnormalities (ACAs) in newly diagnosed acute
      promyelocytic leukemia (APL) patients treated with arsenic trioxide (ATO) as the
      front-line therapy. A series of 271 consecutive APL patients has been
      cytogenetically investigated between 2004 and 2011 in our institution. The
      incidence of ACAs was 27% (46/172) in APL cases with t(15;17). Trisomy 8 was the
      most recurrent abnormality, accounting for 30% (14/46) of patients with ACAs,
      followed by +21 (7%, 3/46) and -7/7q (7%, 3/46). Nine cases (14.1%) were found to
      have additional balanced translocation aberrations, most of them are new and non
      recurrent. Treatment protocols consisted of all-trans retinoic acid (ATRA) and
      chemotherapy with or without the ATO therapy. Overall, patients with and without
      ACAs had similar complete remission (CR) rates (94% and 98%, respectively,
      P=0.344). With a median follow-up of 41 months, univariate analysis showed that
      ACAs did not show any prognostic significance in relapse-free survival (RFS) and
      overall survival (OS). In addition, ATO treatment was an independent favorable
      predictor for RFS. Thus, this data provides insights into cytogenetic features of
      APL, and suggests that ATO-based combination therapy improved RFS in de novo APL
      patients, while ACAs had no impact on prognosis. 

PMID- 23958061
TI  - Oxidative stress leads to increased mutation frequency in a murine model of
      myelodysplastic syndrome.
AB  - The myelodysplastic syndromes (MDS) are characterized by ineffective
      hematopoiesis, dysplasia, and transformation to acute myeloid leukemia (AML).
      Although it has been suggested that additional mutations lead to progression of
      MDS to AML, the causative agent(s) for such mutations remains unclear. Oxidative
      stress is a potential cause, therefore, we evaluated levels of reactive oxygen
      species (ROS) in NUP98-HOXD13 (NHD13) transgenic mice, a murine model for MDS.
      Increased levels of ROS were detected in bone marrow nucleated cells (BMNC) that
      express CD71, a marker for cell proliferation, as well as immature, lineage
      negative bone marrow nucleated cells from NHD13 mice. In addition to the increase
      in ROS, increased DNA double strand breaks and activation of a G2/M phase cell
      cycle checkpoint were noted in NHD13 BMNC. Finally, using an in vivo assay for
      mutation frequency, we detected an increased mutation frequency in NHD13 BMNC.
      These results suggest that oxidative stress may contribute to disease progression
      of MDS to AML through ineffective repair of DNA damage and acquisition of
      oncogenic mutations. 

PMID- 23958063
TI  - Bioenergetic failure correlates with autophagy and apoptosis in rat liver
      following silver nanoparticle intraperitoneal administration.
AB  - BACKGROUND: Deposition and accumulation of silver nanoparticles (Ag-nps) in the
      liver have been shown to induce hepatotoxicity in animal studies. The
      hepatotoxicity may include oxidative stress, abnormalities in energy metabolism,
      and cell death. Studies have indicated that autophagy is an intracellular event
      involving balance of energy, nutrients, and turnover of subcellular organelles.
      The present study was undertaken to test the hypothesis that autophagy plays a
      role in mediating hepatotoxicity in animal after exposure to Ag-nps. Focus was
      placed on interrelationship between energy metabolism, autophagy, apoptosis and
      hepatic dysfunction. METHODS: Sprague Dawley rats were intraperitoneally injected
      with Ag-nps (10-30 nm in diameter) at concentration of 500 mg kg(-1). All animals
      were sacrificed on days 1, 4, 7, 10 and 30 after exposure and blood and liver
      tissues were collected for further studies. RESULTS: Uptake of Ag-nps was quite
      prompt and not proportional to the blood Ag concentration. Declination of ATP (
      64% in days 1) and autophagy (determined by LC3-II protein expression and
      morphological evaluation) increased and peaked on the first day. The ATP content
      remained at low level even though the autophagy has been activated. Apoptosis
      (based on caspase-3 protein expression and TUNEL-positive cells staining) began
      to rise sigmoidally at days 1 and 4, reached a peak level at day 7, and remained
      at the same levels during days 7-30 post exposure. Meanwhile, autophagy exhibited
      a gradual decrease from days 1-10 and the decrease at day 30 was statistically
      significant as compared to day 0 (sham group). Inflammatory reaction
      (histopathological evaluation) was found at day 10 and preceded to an advanced
      degree at day 30 when liver function was impaired. CONCLUSIONS: These results
      indicate that following Ag-nps administration, autophagy was induced; however,
      failure to preserve autophagy compounded with energy reduction led to apoptosis
      and the eventual impairment of liver function. The study provides an in-vivo
      evidence of hepatotoxicity by continuous exposure of Ag-nps in rats.

PMID- 23958064
TI  - Microsatellite loci characterized in the leaf-cutter ant Atta laevigata.
AB  - BACKGROUND: The leaf-cutter ant Atta laevigata (Formicidae: Attini) is an
      agricultural pest largely distributed in the Neotropics and a model organism for
      studies of evolution, speciation and population genetics. Microsatellites are a
      very powerful tool for these kind of studies, but such markers are not available
      for studies on A. laevigata. In the present report, we describe the isolation and
      characterization of nine microsatellite loci in A. laevigata and the testing of
      these markers across other species of leaf-cutter ants. FINDINGS: Nine
      microsatellite loci, consisting of six dinucloeotide, one trinucleotide, one
      tetranucleotide, and one di/trinucleotide repeat motifs, were isolated and
      characterized. Primers and protocols were successfully designed to selectively
      amplify these markers. To test effectiveness of these markers for detailed
      population genetic studies, we genotyped female workers collected from 36
      monogynic nests of A. laevigata and found that eight loci were within Hardy
      Weinberg expectations, while the remaining locus had a deficiency of
      heterozygotes. Micro-Checker analysis of individuals from 55 monogynic nests
      indicated that loci Alae11, Alae24, Alae18 showed signs of null alleles. For the
      remaining six loci, the number of alleles per locus ranged between 2 and 11, with
      expected heterozygosity ranging between 0.07 and 0.88. All of these loci cross
      amplified in other species of Atta. CONCLUSIONS: These six polymorphic
      microsatellite loci should prove useful for future genetic investigations of the
      pest species Atta laevigata, as well as studies of other species of leaf-cutter
      ants in the genus Atta.

PMID- 23958065
TI  - Phylogenetic analysis and victim contact tracing of rabies virus from humans and
      dogs in Bali, Indonesia.
AB  - SUMMARY: The emergence of human and animal rabies in Bali since November 2008 has
      attracted local, national and international interest. The potential origin and
      time of introduction of rabies virus to Bali is described. The nucleoprotein (N)
      gene of rabies virus from dog brain and human clinical specimens was sequenced
      using an automated DNA sequencer. Phylogenetic inference with Bayesian Markov
      Chain Monte Carlo (MCMC) analysis using the Bayesian Evolutionary Analysis by
      Sampling Trees (BEAST) v. 1.7.5 software confirmed that the outbreak of rabies in
      Bali was caused by an Indonesian lineage virus following a single introduction.
      The ancestor of Bali viruses was the descendant of a virus from Kalimantan.
      Contact tracing showed that the event most likely occurred in early 2008. The
      introduction of rabies into a large unvaccinated dog population in Bali clearly
      demonstrates the risk of disease transmission for government agencies and should
      lead to an increased preparedness and efforts for sustained risk reduction to
      prevent such events from occurring in future.

PMID- 23958066
TI  - RGTA-based matrix therapy in severe experimental corneal lesions: safety and
      efficacy studies.
AB  - Corneal alteration potentially leading to ulceration remains a major health
      concern in ocular surface diseases. A treatment that would improve both the
      quality and speed of healing and control the inflammation would be of great
      interest. Regenerating agents (RGTAs) have been shown to stimulate wound healing
      and modulate undesired fibrosis in various in vivo systems. We investigated the
      effects of RGTA-OTR4120((r)) in a rabbit corneal model in order to assess its
      potential use in ocular surface diseases. First, we assessed its safety for 7 and
      28 days using the Draize test criteria in healthy rabbit eyes; then, we
      investigated the effect of a single dose (50MUl, 5MUg) in an alkali-burned cornea
      model. Daily follow-up of clinical signs of healing was scored, and histology was
      performed at D7. RGTA was well tolerated; no signs of ocular irritation were
      observed. In the corneal alkali-burn model, non-RGTA-treated eyes showed
      inflammatory clinical signs, and histology confirmed a loss of superficial
      corneal layers with epithelial disorganization, neovascularization and
      infiltration of inflammatory cells. When compared to NaCl control, RGTA treatment
      appeared effective in reducing clinical signs of inflammation, enhancing re
      epithelialization, and improving histological patterns: edema, fibrosis,
      neovascularization and inflammation. Three to four layers of epithelial cells
      were already organized, stroma was virtually unvascularized and keratocytes well
      implanted in parallel collagen fibers with an overall reorganization similar to
      normal cornea. RGTA appears to be a promising agent for controlling ocular
      surface inflammation and promoting corneal healing and was well tolerated. This
      study offers preclinical information and supports the findings of other
      (compassionate or pilot) studies conducted in patients with various ocular
      surface diseases. 

PMID- 23958067
TI  - Congenital subclavian steal syndrome with multiple cerebellar infarctions caused
      by an atypical circumflex retroesophageal right aortic arch with atretic aberrant
      left subclavian artery.
AB  - A right-sided aortic arch is a rare anomaly with an incidence of 0.1% worldwide
      and is usually associated with a mirror image of all supra-aortic branches or an
      aberrant left subclavian artery. The latter is often associated with a Kommerell
      diverticulum, although it can rarely be hypoplastic or atretic and lead to
      congenital subclavian steal. In most patients, the situation is well-tolerated.
      In this report, we present a case of subclavian steal syndrome with multiple
      cerebellar infarcts in a patient with an atypical right-sided aortic arch and an
      atretic aberrant left subclavian artery arising from a left-sided descending
      thoracic aorta. 

PMID- 23958068
TI  - Managing iliofemoral deep venous thrombosis of pregnancy with a strategy of
      thrombus removal is safe and avoids post-thrombotic morbidity.
AB  - BACKGROUND: Extensive deep venous thrombosis (DVT) during pregnancy is usually
      treated with anticoagulation alone, risking significant post-thrombotic syndrome
      (PTS) in young patients. Catheter-directed thrombolysis (CDT) and operative
      venous thrombectomy have been safely and effectively used in nonpregnant
      patients, demonstrating significant reduction in post-thrombotic morbidity. This
      report reviews short- and long-term outcomes of 13 patients with extensive DVT of
      pregnancy treated with a strategy of thrombus removal. METHODS: From 1999 to
      2013, 13 patients with iliofemoral DVT during pregnancy were offered CDT,
      pharmacomechanical thrombolysis (PMT), and/or venous thrombectomy. Gestational
      age ranged from 8 to 34 weeks. Fetal monitoring was performed throughout
      hospitalization. Radiation exposure was minimized with pelvic lead shields, focal
      fluoroscopy, and limited angiographic runs. Follow-up included objective vein
      evaluation using venous duplex and PTS assessment using the Villalta scale.
      RESULTS: CDT and/or PMT were used in 11 patients. Two patients underwent venous
      thrombectomy alone, and one patient had operative thrombectomy as an adjunct to
      CDT and PMT. Each patient had complete or near-complete thrombus resolution and
      rapid improvement in clinical symptoms. Eight of 11 having CDT or PMT underwent
      venoplasty and stenting of the involved iliac veins. Twelve of the 13 delivered
      healthy infants at term. One patient opted for termination of her pregnancy. Mean
      patient and gestational ages were 26 years and 26 weeks, respectively. Mean
      follow-up was 1.3 years, with only one recurrence. Duplex ultrasonography
      demonstrated patent veins in all but one patient and normal valve function in 10
      patients. Eleven patients had Villalta scores <5 (considered normal), with a mean
      score of 0.7. CONCLUSIONS: Extensive DVT of pregnancy can be effectively and
      safely treated with a strategy of thrombus removal, resulting in a patent venous
      system, normal valve function in many, prevention of PTS, and reduction in
      recurrence.

PMID- 23958069
TI  - Predisposing factors, management, and prognostic evaluation of acute carotid
      blowout syndrome.
AB  - BACKGROUND: Massive hemorrhages occur in 6%-10% of patients with advanced cancer.
      Acute carotid blowout syndrome is the most severe massive hemorrhagic
      complication in head and neck cancer patients. METHODS: This was a single
      institute, retrospective, case control study. A total of 45 patients were
      enrolled in this study. The predisposing factors, management, and prognosis of
      acute carotid blowout syndrome were evaluated. RESULTS: Among the baseline
      characteristics, the site of the primary tumor (P = .003), origin of bleeding (P
      = .048), method of intervention (P = .005), and time to intervention (P = .006)
      were significantly different factors between survivor and nonsurvivor patients.
      After 24 hours of onset, a Glasgow Coma Scale score (P = .000), the use of
      inotropic agents (P = .007), and neutrophil-to-lymphocyte ratio (P = .019) were
      significantly predicting factors for outcome. Multivariate logistic regression
      analyses revealed bleeding from common carotid artery was an independent factor
      for long-term survival (odds ratio, 25.951; 95% confidence interval [CI], 1.373
      490.441; P < .030). The median overall survival of survivors and nonsurvivors
      were 12.1 (range, 3.7-118.7; 95% CI, 4.33-54.87) and 11.9 (range, 0.7-53.5; 95%
      CI, 5.78-25.69) months, respectively (P = .092). CONCLUSIONS: Early and
      aggressive intervention is important for the successful management of acute
      carotid blowout syndrome. The Glasgow Coma Scale score, the use of inotropic
      agents, and neutrophil-to-lymphocyte ratio 24 hours after the onset were
      predictive factors for patients' outcomes. Bleeding from common carotid artery is
      an independent prognostic factor in multivariate analysis. Long-term survival can
      be achieved after successful management.

PMID- 23958070
TI  - Sources of error in the measurement of aortic diameter in computed tomography
      scans.
AB  - OBJECTIVE: This study was conducted to determine the differences in the diameter
      of the thoracic aorta when measured from electrocardiographic (ECG)-gated and
      nongated computed tomography (CT) angiography. Another aim was to define the
      difference in the aortic diameter when it is measured at peak systole and end
      diastole in ECG-gated scans. METHODS: The gated and nongated CT angiograms of 27
      patients (mean age, 58 +/- 16 standard deviation [SD] years) obtained on a 256
      slice multidetector CT scanner were used. The transverse and anteroposterior
      diameters and the lumen areas were measured at 1, 4, and 8 cm below the origin of
      the left subclavian artery. RESULTS: There was a significant difference in the
      aortic measurements of diameter between gated and nongated scans found in samples
      taken at 1, 4, and 8 cm distal to the left subclavian artery (P < .0001). We
      found a considerable difference between the systolic and diastolic diameters (P <
      .0001). The maximum change in diameter between systole and diastole was 2.9 +/-
      0.9 (SD) mm (14.5%, P < .0001) at 1 cm, 5.4 mm (22.6%; median, 1.7 mm; P < .0001)
      at 4 cm, and 4.4 mm (16.9%; median, 1.3 mm; P < .0001) at 8 cm. There was a
      significant difference between the transverse and anteroposterior diameters in
      systole and diastole at all locations (P < .0001): The maximum change in diameter
      between transverse and anteroposterior diameters in systole was 5.4 +/- 1.1 (SD)
      mm (15.7%, P < .0001) at 1 cm, 5.8 mm (19%; median, 1.4 mm; P < .0001) at 4 cm,
      and 5 mm (15%; median, 1.02 mm; P < .0001) at 8 cm. There was also a substantial
      difference between measuring the transverse diameter directly and deriving it
      from the lumen area (P < .0001). CONCLUSIONS: Our results showed an important
      difference between systolic and diastolic diameters measurements in ECG-gated
      scans. The standard protocol for measuring aortic diameters in gated scans of the
      thoracic aorta uses images at end diastole because the lack of wall motion at
      this time provides better resolution. This is likely to result in undersizing
      that, in some instances, may threaten stability and the proper seal of the stent
      graft. The dimensions of the aorta in a gated CT should be measured at peak
      systole rather than the conventional end diastole used today. Most medical
      centers use nongated CT or gated CT scans in end diastole to calculate sizes of
      endografts. In view of our findings, the latter method could result in potential
      complications.

PMID- 23958071
TI  - Endovascular repair of aortic arch false aneurysm with branched endograft.
AB  - This case report describes the use of a customized branched device for the
      treatment of a distal anastomotic false aneurysm in an ascending to descending
      interposition graft in a 34-year-old Jehovah's Witness with congenital aortic
      arch interruption. A single branched customized stent graft device was used to
      successfully exclude the false aneurysm. The procedure was challenging due to the
      abnormal congenital anatomy. The planning, operative technique, and successful
      execution are described in this case report. 

PMID- 23958072
TI  - Trehalose protects against spinal cord ischemia in rabbits.
AB  - OBJECTIVE: This study tested to see if trehalose, a cytoprotective disaccharide,
      protects against spinal cord ischemia in a rabbit model. METHODS: The infrarenal
      aorta was mobilized in four groups of 10 rabbits. In groups I, II, and III, it
      was clamped proximally and distally for 20 minutes. In group I, the clamped aorta
      was infused at 2.5 L/min for 2 hours with lactated Ringer's (LR) solution. In
      group II, the clamped aorta was infused with 5% trehalose in LR. LR was
      administered intravenously (2.0 mL/min) in groups I and II starting 30 minutes
      before clamping. In group III, 5% trehalose in LR was infused intravenously only.
      Group IV was a sham-operated control group without aortic clamping. At 8, 24, and
      48 hours after reperfusion, hind limb function was scored using the Tarlov score
      (paralysis = 0, perceptible joint movement = 1, good joint movement but unable to
      stand = 2, able to walk = 3, normal = 4). Histologic analysis and electron
      microscopy were performed on anterior horn cells. RESULTS: The Tarlov scores in
      groups I, II, and III were, respectively, 1.1 +/- 1.4, 3.5 +/- 0.5, and 2.9 +/-
      0.9 at 8 hours; 0.8 +/- 1.2, 3.9 +/- 0.3, and 2.9 +/- 0.9 at 24 hours; and 0.6 +/
      0.7, 3.9 +/- 0.3, and 2.7 +/- 0.9 at 48 hours after reperfusion. Group IV scores
      were normal (4 +/- 0) at all assessments. These scores were higher in groups II
      and III than in group I (P < .01) at all assessments. Scores at 24 and 48 hours
      were higher in group II than in group III (P < .05). In group III, delayed
      paraparesis developed in one rabbit at 24 hours and in two more at 48 hours.
      Histopathologic analysis showed the number of normal neurons was higher in groups
      II (P < .0001), III (P = .006), and IV (P < .0001) vs group I. Electron
      microscopy confirmed preserved neuronal cell ultrastructure in rabbits with
      normal limb function. CONCLUSIONS: Transaortic trehalose infusion was protective
      against paraplegia, whereas intravenous trehalose reduced spinal cord ischemia.
      This study was preliminary and further studies are needed.

PMID- 23958073
TI  - A comparison of the EZ-Blocker with a Cohen Flex-Tip blocker for one-lung
      ventilation.
AB  - OBJECTIVES: The EZ-Blocker (IQ Medical Ventures BV, Rotterdam, Netherlands) is a
      newly designed device for one-lung ventilation. The aim of this study was to
      compare the effectiveness of the Cohen Flex-Tip bronchial blocker (Cook,
      Bloomington, IN) and the EZ-Blocker for one-lung ventilation during thoracic
      surgery. DESIGN: Randomized and prospective. SETTING: A university hospital.
      PARTICIPANTS: This study included 40 patients undergoing thoracic surgical
      procedures. INTERVENTIONS: Patients were assigned to 2 study groups: Patients who
      received the Cohen Flex-Tip blocker were assigned to the Cohen group, and
      patients who received the EZ-Blocker were assigned to the EZ group. In both
      groups, fiberoptic guidance was used during placement of the bronchial blockers.
      Comparisons between the groups included the time to correct placement, the
      incidence of malpositioning, and the satisfaction level of the surgeon (good,
      fair, poor). MEASUREMENTS AND MAIN RESULTS: One-lung ventilation was achieved
      successfully for all patients. The time to correct placement (mean+/-SD) was
      significantly shorter in the EZ group (146+/-56 seconds) compared with the Cohen
      group (241+/-51 seconds; p=0.01). The incidence of malpositioning was
      significantly lower in the EZ group compared with the Cohen group (p=0.018).
      Surgeon satisfaction was similar in both groups. CONCLUSIONS: In this study, both
      bronchial blockers provided similar surgical exposure during thoracic procedures.
      The EZ-Blocker had a shorter time to correct positioning and less frequent
      intraoperative malpositioning.

PMID- 23958074
TI  - Efficacy of perioperative oral triiodothyronine replacement therapy in patients
      undergoing off-pump coronary artery bypass grafting.
AB  - OBJECTIVE: The aim of this study was to assess the effects of oral
      triiodothyronine (T3) therapy on postoperative thyroid hormone concentrations,
      hemodynamic variables, and outcomes. DESIGN: A prospective, randomized,
      controlled, double-blind study. SETTING: Cardiac operating room at a single
      institution. PARTICIPANTS: One hundred patients undergoing elective off-pump
      coronary artery bypass graft surgery. INTERVENTIONS: Patients received either 20
      MUg of oral T3 or placebo every 12 hours starting 20 minutes before anesthetic
      induction, for a total of 4 doses. MEASUREMENTS AND MAIN RESULTS: Plasma
      concentrations of thyroid hormones were measured serially before surgery, upon
      arrival in the intensive care unit, and 12, 24, and 36 hours after surgery.
      Hemodynamic variables also were recorded serially. Postoperative inotrope
      requirement and major morbidity endpoints were assessed. Serum T3 concentrations
      were significantly higher with fewer patients having T3 concentrations below the
      normal range in the T3 group than the placebo group throughout the postoperative
      period. Hemodynamic variables, postoperative inotrope requirement, and outcome
      variables showed no differences between the groups. CONCLUSIONS: Oral T3 therapy
      significantly attenuated the postoperative decline in T3 concentrations in
      patients undergoing off-pump coronary artery bypass graft surgery. The lack of
      apparent clinical benefit merits further investigations in patients with reduced
      cardiac performance.

PMID- 23958075
TI  - Intraoperative echocardiographic diagnosis of inferior vena cava stenosis after
      cardiopulmonary bypass.

PMID- 23958076
TI  - Diverticular abscess successfully treated by endoscopic transluminal drainage.

PMID- 23958077
TI  - Aggressive strategy for the treatment of synchronous metastatic anal squamous
      cell carcinoma.

PMID- 23958078
TI  - Preparing the nursing student for internship in a pre-registration nursing
      program: developing a problem based approach with the use of high fidelity
      simulation equipment.
AB  - AIM: This paper aims to explore the development and evaluation results of a
      simulated skills package designed using a problem based learning approach with
      general nursing students. BACKGROUND: Internationally, the use of high fidelity
      simulated learning environments has escalated. This has occurred as a result of
      growing concerns relating to patient safety, patient litigation, lack of clinical
      opportunities for student nurses to gain experience and integration of new
      teaching methods into nursing curricula. There are however both proponents and
      opponents to the value of simulation and high fidelity simulation within nursing
      education. METHODS: This study was conducted in an Irish school of nursing. A
      simulated learning support package was developed by nurse educators and piloted
      with 134 third year nursing students. This was evaluated using a questionnaire in
      which 87 students responded. FINDINGS: Students generally found the simulation
      sessions realistic and useful in developing clinical skills, knowledge and
      confidence for clinical practice. However student issues regarding support with
      preparation for the session were highlighted. Also, the need for a more
      formalised structure for debriefing following the simulation sessions were
      identified. CONCLUSION: It is hoped that this paper will provide nurse educators
      with some guidance to aid future development of innovative and interactive
      teaching and learning strategies.

PMID- 23958079
TI  - Understanding nursing students' perspectives on the grading of group work
      assessments.
AB  - Grading group work assessments so that students perceive the grade to be fair to
      all group members is sometimes challenging. This is particularly important in a
      higher education environment that is increasingly concerned with student
      perceptions of teaching quality and satisfaction. This article reports on
      research that compared undergraduate nursing students perceptions of two
      different approaches to the grading of group work assessment. A survey design was
      used to identify students' perspectives and preferences for different group work
      assessment methods. Participants were undergraduate bachelor of nursing students
      from a large, metropolitan university in Australia. Data analysis indicated that
      the perceptions of students around group work assessments changed little as they
      progressed across the program, although students who had experienced the
      calculation of individual grades for a group assessment preferred this approach.
      Many believed the grading of group assessments penalised good students and were
      less reliable than individual assessments. Students maintained the belief that
      teamwork skills were essential for the registered nurse role. In conclusion group
      work assessment should only be used when it is the best assessment method to
      demonstrate student learning of specific objectives. The weighted mark approach
      is the group work assessment grading approach of choice. 

PMID- 23958081
TI  - Changes and recovery of soil bacterial communities influenced by biological soil
      disinfestation as compared with chloropicrin-treatment.
AB  - Soil bacterial composition, as influenced by biological soil disinfestation (BSD)
      associated with biomass incorporation was investigated to observe the effects of
      the treatment on the changes and recovery of the microbial community in a
      commercial greenhouse setting. Chloropicrin (CP) was also used for soil
      disinfestation to compare with the effects of BSD. The fusarium wilt disease
      incidence of spinach cultivated in the BSD- and CP-treated plots was reduced as
      compared with that in the untreated control plots, showing effectiveness of both
      methods to suppress the disease. The clone library analyses based on 16S rRNA
      gene sequences showed that members of the Firmicutes became dominant in the soil
      bacterial community after the BSD-treatment. Clone groups related to the species
      in the class Clostridia, such as Clostridium saccharobutylicum, Clostridium
      tetanomorphum, Clostridium cylindrosporum, Oxobacter pfennigii, etc., as well as
      Bacillus niacini in the class Bacilli were recognized as the most dominant
      members in the community. For the CP-treated soil, clones affiliated with the
      Bacilli related to acid-tolerant or thermophilic bacteria such as Tuberibacillus
      calidus, Sporolactobacillus laevolacticus, Pullulanibacillus naganoensis,
      Alicyclobacillus pomorum, etc. were detected as the major groups. The clone
      library analysis for the soil samples collected after spinach cultivation
      revealed that most of bacterial groups present in the original soil belonging to
      the phyla Proteobacteria, Acidobacteria, Bacteroidetes, Gemmatimonadetes,
      Planctomycetes, TM7, etc. were recovered in the BSD-treated soil. For the CP
      treated soil, the recovery of the bacterial groups belonging to the above phyla
      was also noted, but some major clone groups recognized in the original soil did
      not recover fully. 

PMID- 23958080
TI  - Protective effects of in vitro treatment with zinc, d-aspartate and coenzyme q10
      on human sperm motility, lipid peroxidation and DNA fragmentation.
AB  - BACKGROUND: Spermatozoa are extremely vulnerable to oxidative stress caused by
      the unbalance between concentrations of reactive oxygen species and antioxidant
      scavenging systems present inside the male reproductive tract. In spite of a
      large number of clinical studies that claimed the beneficial effects of
      antioxidant oral administration on sperm physiology and fertility, only a few
      studies were addressed to evaluate their effects on spermatozoa in vitro. Main
      aims of the present study were to assess the influence of zinc, D-aspartate and
      coenzyme Q10, included in the dietary supplement Genadis (Merck Serono), on human
      sperm motility, DNA fragmentation and lipid peroxidation. METHODS: Semen samples,
      obtained from forty-four patients (23-30 years of age) were enrolled in this
      study, twenty-four were normospermic and twenty patients were oligospermic. Semen
      samples were analysed for sperm progressive motility and kinetics through
      computer assisted analysis, DNA fragmentation and lipid peroxidation. RESULTS:
      Main results showed that in both normo and oligospermic samples, total and
      progressive sperm motility is maintained by in vitro treatment with zinc, D
      aspartate and coenzyme Q10, whereas a significant decrease of these parameters
      occurs in parallel samples incubated in medium alone. Zinc, D-aspartate and
      coenzyme Q10 also prevented the decrease of sperm kinetics but such an effect was
      highly significant only in oligospermic samples. Moreover, they also protected
      spermatozoa by the increase of DNA fragmentation and lipid peroxidation.
      CONCLUSIONS: Zinc, D-aspartate and coenzyme Q10 exert a direct protective effect
      on human spermatozoa preventing the decrease of motility and the increase of DNA
      fragmentation and lipid peroxidation during in vitro culture.

PMID- 23958082
TI  - Surgical utility of the Lanz classification of median nerve ramification.
AB  - The authors comment on the Lanz classification of the median nerve ramification
      at wrist level. The authors outline the importance of having very good knowledge
      of this classification for hand surgeons, plastic surgeons and neurosurgeons, in
      order to prevent iatrogenic lesions of the median nerve branches at wrist level.
      The regional anatomy is of utmost importance for carpal tunnel syndrome surgery,
      especially the mini-invasive and endoscopic techniques. 

PMID- 23958083
TI  - Outcome of liver transplantation for hepatocellular carcinoma -- a single center
      experience.
AB  - BACKGROUND & AIMS: Liver transplantation (LT) is a promising treatment for
      patients with liver cirrhosis associated with hepatocellular carcinoma (HCC). The
      aim of our study was to evaluate our experience regarding the clinical and
      pathological staging of HCC in patients who underwent LT, as well as recurrence
      free and overall survival. METHODS: From January 2006 to December 2011, 38
      patients with diagnosis of HCC, underwent LT in our Center. Demographic,
      clinical, imaging and pathologic information were recorded. A Cox proportional
      hazards survival analysis was performed in order to identify significant
      predictors of tumor recurrence and patient's death after LT. RESULTS: Eighteen
      patients (47.4%) in our study group were within Milan criteria. The mean follow
      up was 22 months and the recurrence rate of HCC after LT was 13.2%. The 1, 3-
      year recurrence free survival rates were 85%, 74.3% respectively. The 1 and 3
      year overall survival rates were 83.5% and 63.6% respectively. No significant
      predictor for HCC recurrence was identified in our study group by survival
      analysis, taking into account 13 different variables. As independent predictors
      of patient'ss death after LT for HCC however, the presence of diabetes mellitus
      (p=0.001), presence of more than 3 HCC nodules (p=0.03) and tumor recurrence
      after LT (p=0.03) were identified by multivariate Cox proportional hazards
      survival analysis. CONCLUSION: In our cohort HCC recurrence rate after LT was
      13.2%. Diabetes mellitus, presence of more than 3 HCC nodules and HCC recurrence
      were significant predictors of poor overall survival after LT.

PMID- 23958084
TI  - Superior socio-medical alternative to feeding gastrostomy and jejunostomy in
      advanced esophago-gastric junction adenocarcinoma.
AB  - INTRODUCTION: The diagnosis of esophago gastric junction adenocarcinoma often
      occurs when the neoplastic process is surprised in advanced stages and blocks the
      esophageal-gastric junction causing dysphagia, stages in which curative therapy
      is more likely impossible to be accomplished. In these cases, the treatment goal
      is mainly to provide feeding capacity as naturally as possible and to start the
      adjuvant oncological treatment. The use of endoscopic esophageal prostheses
      provides the patient with the possibility to be fed orally and with a good social
      integration, but due to the technical incapacity to cross the tumoral stenosis
      with the endoscope, or due to the endoscopist s concerns regarding the sensitive
      areas (poles of the esophagus), there are reluctances in respect to this method
      (on average 20%). MATERIAL AND METHOD: We conducted a retrospective study aimed
      to determine the optimal therapeutic modality depending on the evolutive stages
      of the disease and to analyse the justification of the original procedure of
      laparogastroscopic esophageal stenting through tumoral drilling as a technical
      alternative to the reluctances or failures of endoscopic prosthesis and as a
      biological and social solution to the disabling gastrostomy for patients with
      advanced esophageal-gastric junction adenocarcinoma. RESULTS AND DISCUSSIONS:
      Staging was disarming, most patients were diagnosed in advanced stages, fact also
      supported by literature. Regarding esophageal stenting by transtumoral drilling,
      the results are significant especially in terms of postoperative morbidity
      CONCLUSIONS: Although our study regarding laparogastroscopic stenting by
      transtumoral drilling in esophago-gastric junction adenocarcinoma is limited,
      this original procedure brought us satisfaction whenever we used this approach.

PMID- 23958085
TI  - Surgery of tumors of the third ventricle region.
AB  - BACKGROUND: The third ventricle is located in the center of the brain, surrounded
      by critical structures. The authors reported their experience in the surgical
      treatment of tumors originated from or expanding within the third ventricle,
      analysing the postoperative results and patient's outcome. MATERIAL AND METHODS:
      We performed a retrospective study on 120 patients, who had been operated in our
      neurosurgical department for tumors of the third ventricle and adjacent region
      over the last 21 years. According to their place of origin, these tumors were
      divided into primary tumors of the third ventricle (69 cases) and tumors
      developed from the surrounding structures (51 cases). The patients were operated
      on via a transcallosal-transventricular approach (58.34%), transcortical parieto
      occipital approach (26.67%) or subfrontal approach (15%). Microsurgery has been
      used in all cases. In 20 patients (16.67%), preoperative ventricular drainage was
      performed. Stereotactic procedures were not used in this study. RESULTS: The
      overall mortality in this series was 11.67% (14 120 died). The death was directly
      correlated to the surgery in 8 cases, to general complications in 3 cases, to
      recurrence of the tumor in 2 cases, and to shunt malfunction in one case.
      Perioperative good evolution (GOS 5) was noted in 54 patients (45%), but at one
      year follow-up, good neurological evolution was recorded in 72 patients (60%).
      The long-term neurological outcome recorded neurological impairments in 21.42% of
      patients, a permanent diabetes insipidus in 5.1% of patients and the persistence
      of neuropsychological deficits in 28.57%. The recurrence of the tumor has been
      encountered in 16 patients (13.34%). CONCLUSIONS: Transcallosal approach remains
      the best method for the microneurosurgical treatment of third ventricle tumors.
      This route provides the capability for a superior visualization of the entire
      cavity of the third ventricle through different corridors, and permanent
      neurological and neuropsychological deficits are not frequent.

PMID- 23958086
TI  - The surgical treatment for Crohn's disease.
AB  - INTRODUCTION: Crohn's disease is a chronic idiopathic medical and surgical
      disease, in which the transmural intestinal inflammatory process frequently leads
      to complications such as strictures or fistulae. The disease is considered to be
      the result of an imbalance between the proinflammatory mediators and the anti
      inflammatory ones; it can be localized on any segment of the gastrointestinal
      tract, but it especially affects the terminal ileum. The purpose of the study is
      to assess Crohn's disease from the point of view of the complications requiring
      surgical treatment, the manner in which they are solved, as well as the
      postoperative evolution. MATERIAL AND METHOD: we followed retrospectively the
      patients hospitalized and operated in our department during the period January
      2001 - December 2011. We examined the clinical observation charts, the
      paraclinical investigations, the surgical protocols and the histopathological
      results. RESULTS: the 11 patients included in the study underwent 13 surgical
      interventions. Their ages were comprised between 16 and 67, the average age being
      42.9. The men women ratio was 7 4 (1.75); the interventions performed were
      segmental enterectomies, right ileo- hemicolectomy, ileotransverse anastomosis,
      an exploratory laparotomy and an exploratory laparoscopy. CONCLUSIONS: the
      purpose of the treatment of Crohn's disease is to obtain the best possible
      clinical, laboratory and paraclinical control of the inflammatory process with
      the least adverse reactions to the medication. The surgical indications for the
      treatment of the disease are imposed by severe complications such as perforation,
      stenosis, fistulisation and even malignancy. Consequently, although Crohn's
      disease is a chronic disease with many relapses, the correct medical and surgical
      treatment helps patients to maintain a reasonable quality of life, with a good
      prognosis and a very low mortality rate.

PMID- 23958087
TI  - Analysis of several BRCA1 and BRCA2 mutations in a hospital-based series of
      unselected breast cancer cases.
AB  - BACKGROUND: The distribution of BRCA mutations varies significantly between
      populations. The spectrum of BRCA1 and BRCA2 mutations in breast cancers in the
      Romanian population is incompletely known. The aim of the present study is to
      investigate the presence of nine BRCA mutations in patients with breast cancer
      identified in a surgical clinic from Bucharest. METHODS: Unrelated women
      diagnosed with breast cancer from Coltea Hospital (n=114) and healthy controls (n
      = 150) were selected for this study. Seven mutations in BRCA1 (185delAG,
      5382insC, 943ins10, E1250X, 1294del40, E1373X, R1443X) and two in BRCA2 (IVS16
      2A4G and 6174delT) were tested using PCR based protocols. In addition, the
      presence of BRCA1 185delAG, BRCA1 5382insC, BRCA2 6174delT mutations were tested
      with a post amplification mutation detection system, based on the ELISA method.
      RESULTS: Two patients with sporadic breast cancer (2%) and one patient with
      family history of the disease (7.14%) have the BRCA1 5382insC mutation. No other
      mutation was detected in patient and control groups. The mutations were not
      present in the control lot. CONCLUSIONS: Our results indicate that BRCA1 5382insC
      is a common mutation in Romanian women with breast cancer (3 114).

PMID- 23958088
TI  - Evaluation of colorectal adenocarcinomas at single-institution with respect to
      microsatellite instability.
AB  - BACKGROUND AND AIM: Hereditary non-poliposis colorectal cancers exhibit a high
      rate of microsatellite instability. Comparative studies involving stage and other
      prognostic parameters demonstrate a better prognosis in the presence of
      microsatellite instability versus colon cancers without microsatellite
      instability. METHODS: Our study included 608 cases diagnosed with colorectal
      adenocarcinoma by our laboratory between 2004-2010. The cases were re-evaluated
      with respect to criteria defined for MSI, taking into consideration age, anatomic
      localization, and histopathological criteria. Immunohistochemical study was
      performed in appropriate blocks for using MLH-1, MSH-2, MSH-6, and PMS-2.
      RESULTS: The specimens were re-evaluated according to the histological criteria
      defined for microsatellite instability. Anti-MLH-1, anti-MSH-2, anti-MSH-6, and
      anti-PMS-2 antibodies were applied to the paraffin blocks of 27 cases which
      presented morphological criteria suggestive of DNA repair mutation and had a high
      Mspath score. Immunohistochemical study with MLH-1, MSH-2, MSH-6, and PMS-2 for
      the analysis of mismatch repair was refined using the cases with higher Mspath
      scores. CONCLUSIONS: In this study, we reviewed the clinical and
      histopathological features of 608 cases with colorectal adenocarcinoma diagnosed
      in our laboratory between 2004-2010 and assessed pathological features in terms
      of microsatellite instability. The results were discussed in view of the
      literature.

PMID- 23958089
TI  - Optimizing the indication for breast-conservative surgery (BCS) in patients with
      locally-advanced breast cancer.
AB  - BACKGROUND: The main benefit of neoadjuvant chemotherapy is a reduction in tumor
      size, which allows breast-conserving surgery (BCS) in patients who otherwise
      would have required a mastectomy. Breast magnetic resonance (MRI) has been
      proposed to evaluate tumor extent after neoadjuvant chemotherapy, to determine
      which patients have become eligible for BCS. AIM: The aim of our study was to
      determine how the association of breast MRI to routine clinical and radiologic
      assessment of the tumor at initial presentation, and after chemotherapy, affects
      the overall surgical decision process. MATERIAL AND METHODS: 54 women with stage
      IIB-IIIB breast cancer were prospectively enrolled in a study investigating the
      effects of MRI on the surgical decision. RESULTS: Surgical plan was changed from
      BCS to radical mastectomy in 6 cases (13.04%). As a result of using MRI in
      evaluating disease extent, 21.73% of valuable data were added by MRI (pectoralis
      major muscle and skin invasion, multifocal multicentric disease). Due to MRI
      examination 28 (60.86%) of the patients with operable breast cancer after
      neoadjuvant chemotherapy, were eligible for BCS. CONCLUSIONS: Our study
      demonstrates that MRI is the most accurate in determination of tumor size and
      extent, and in establishing eligibility for BCS.

PMID- 23958090
TI  - Unusual malignant tumors of the thyroid gland.
AB  - BACKGROUND: Although situated on the last places among the statistical hierarchy
      of human malignancies, thyroid cancers (TC) are the most common tumors of the
      endocrine system. Follicular epithelium neoplasms account for more than 90% of
      these lesions with a favourable prognosis, while resting tumors (medullary,
      anaplastic, lymphoma, sarcoma etc) generally present a rapid unfavorable
      evolution with a low rate of survival. PATIENTS AND METHODS: In a series of 464
      thyropathies personally treated, 72 cases of TC (15.5%) were identified. Fifty
      seven patients presented epithelial TC a 34 papillary variant, 20 follicular
      variant and 8 mixed forms. Alongside these there were two medullary TC, 9
      anaplastic TC and insular TC, and primary lymphoma and metastasis to the thyroid
      of a lung carcinoma each single case. Four cases have been described in patients
      who were aged 2-6 years at the time of the Chernobyl disaster. Out of the common
      types, based on our own taxonomic criteria, we selected a group of 36 TC with
      unusual clinical, histological and behavioural characteristics or particular
      pathological associations. RESULTS: Seven cases of occult TC, 7 cases with
      precessive adenopathy TC and 11 patients with TC associated with hyperthyroidism
      were registered. All of them underwent adapted thyroidectomies in which the
      presence of cancer was decisive for the extent of surgery. Medullary, insular and
      anaplastic TC were the most aggressive lesions and even extended surgery and
      complementary therapy failed to improve the prognosis of these patients. In the
      same category we included the cases presenting the coexistence of two TC types,
      pathologic dedifferentiation in recurrences and concurrent presence of another
      endocrine or nonendocrine cervical lesion. The a surgical dogma of total
      thyroidectomy cannot always be respected, so complementary therapeutic solutions
      must be applied. RESULTS were complex, registering steady recoveries in occult,
      hyperfunctioning and even in coexisting pathological lesions, but many
      recurrences and reinterventions with poor survival rates (a few weeks up to 2
      years) in cases with reduced or absent histologic differentiation were also
      noted. Some lesions were inoperable. DISCUSSIONS AND CONCLUSIONS: Increasing
      clinician, surgeon and pathologist awareness of these distinct, but not rare
      anatomoclinical contingencies could contribute to their adequate diagnosis and
      treatment. Recent progress in knowledge of molecular carcinogenesis and promising
      successes of targeted chemotherapy trials with new drugs offer promising
      perspectives in the management of advanced or metastatic TC. Surgery still
      remains the cornerstone treatment for thyroid cancers.

PMID- 23958091
TI  - Incidental papillary thyroid microcarcinoma: is completion surgery required?
AB  - BACKGROUND: The indications for completion surgery in patients with thyroid
      papillary microcarcinoma (PMC), incidentally found in thyroids removed for benign
      conditions, remains a subject of debate. METHODS: In a retrospective,
      transversal, cohort study of 187 incidental PMCs, found during histological
      examination of the thyroid gland in 2168 patients operated for benign thyroid
      conditions, we evaluated the influence of initial and completion surgery on
      pathological features associated to local recurrence and cancer-related
      mortality. RESULTS: In the patients with almost total or total thyroidectomy at
      the first operation, lymphadenectomy of lymph nodes with features suggestive of
      malignancy on postoperative ultrasound resulted in a statistically significant (p
      0.01) increase of node positive patients in pathological examination. Completion
      surgery in 38 out of 42 patients who underwent less than a total thyroidectomy
      doesn't result in a significant increase of tumor size, number, multifocality,
      bilaterality, invasion or nodal metastases. There were no significant differences
      in postoperative complications between the two groups. CONCLUSIONS: In patients
      with less than total thyroidectomy and incidentally found PMC in resection
      specimens, 1-5 mm in greatest dimension and without extrathyroidal extension,
      completion surgery was not followed by a significant increase of pathological
      features associated to cancer related morbidity and mortality.

PMID- 23958092
TI  - Multiple malignant tumors.
AB  - BACKGROUND: Due to the improvement in diagnosis and therapy for certain malignant
      tumors, we are now faced with patients who develop in time multiple malignancies.
      METHODS: We conducted a retrospective analysis of the patients diagnosed with at
      least two primary cancers that were admitted and treated in Cluj-Napoca Municipal
      Hospital. The study followed patients for a period of 7.5 years. RESULTS: We
      included in the present study 217 patients (4.33%) with two or more malignant
      primary tumors from 5003 cases diagnosed with a primary cancer. The most common
      sites for multiple malignant tumors were related to the breast, colorectum,
      urinary bladder, prostate and kidneys. CONCLUSIONS: We should always take into
      consideration the possibility of synchronous tumors and we have to keep in mind
      that a successful treatment of cancer might not prevent the onset of another
      primary mass.

PMID- 23958093
TI  - Gastro-omental free flap in oro/hypopharyngeal reconstruction after enlarged
      ablative surgery for advanced stage cancer.
AB  - Reconstruction of complex mucocutaneous defects after ablative surgery for
      advanced cancer of the oropharynx, hypopharynx and larynx (Stages III and IV of
      disease according to TNM classification) with previous radiotherapy is a
      challenging problem for the plastic surgeon. The gastroomental free flap provides
      in these cases both a reliable mucosal lining of the digestive tract and soft
      tissue coverage in the neck. One-stage surgical excision and reconstruction
      improves the quality of life by reducing the hospitalization and providing
      recovery of the swallowing function. BACKGROUND: The method of reconstruction of
      the complex mucocutaneous defects that usually occur after extensive ablative
      surgery associated with radiotherapy for advanced malignant lesions of the
      oropharynx, hypopharynx and larynx should provide both digestive tract
      reconstruction and soft tissue coverage of the neck. The purpose of the article
      is to report our experience with the use of the gastroomental free flap for the
      reconstruction of such complex defects of the oro-and hypopharynx. METHOD: Gastro
      omental free flap was used for one-stage reconstruction of complex defects of the
      oropharynx in four cases and hypopharynx in eleven cases between December 1990
      and December 2008 after extensive ablative surgery for cancer. All fifteen
      patients had received previous irradiation. In all cases the tumor ablation was
      associated with neck dissection. RESULTS: There was one flap failure in this
      series (6.67%). Complications included: two cases of gastric outlet obstructions,
      one case of mild superficial bleeding of the transplanted gastric mucosa and
      three fistulas formed. Thirteen patients had adequate swallowing function after
      reconstruction of the digestive tract. CONCLUSION: Gastro-omental free flap
      represents a reliable and valuable solution in covering of extended and complex
      defects in the oral and cervical area following advanced cancer ablation.

PMID- 23958094
TI  - Considerations on gastroschisis repair.
AB  - BACKGROUND: Although primary closure of the gastroschisis is possible in many
      cases, there have been various strategies published and materials used to cover
      the eviscerated bowel when the abdominal wall defect cannot be closed in one
      step, providing bowel protection and reduction of heat and fluid loss. There have
      been suggestions of coverage materials such as skin graft, lyophilized dura mater
      graft, free flap corium and meshed skin graft (1,2). PURPOSE: We highlight an
      alternative repair method of gastroschisis in those cases where there is a
      disproportion between the amount of eviscerated organs and the hypoplastic
      abdominal cavity. If in this case primary closure of the abdominal wall is
      chosen, the difference in volume can cause a significant increase in
      intraabdominal pressure. METHOD: In some cases, when complete primary closure was
      not possible, we used an alternative method to repair the parietal defect using
      umbilical cord patch. RESULTS: This technique creates a mesothelial surface in
      contact with the bowel. Remote tracking of these patients showed excellent
      results. CONCLUSIONS: This technique is easy to apply and very useful for infants
      with gastroschisis especially when primary closure is not possible. The use of
      autologous material, in this case as the umbilical cord, has several advantages,
      including wide availability, a lower rate of infection and significantly reduced
      costs.

PMID- 23958095
TI  - Gastroschisis treatment: what are the causes of high morbidity and mortality
      rates?
AB  - INTRODUCTION: Gastroschisis is one of the most common birth defects of the
      anterior abdominal wall, in recent decades being witnessed a significant increase
      in the survival of children with such a condition. This study aims to discover
      the causes of the increased perinatal morbidity and mortality rates from
      gastroschisis in our country. METHODS: Retrospective study on 54 infants with
      gastroschisis. Patient data were statistically processed and the demographic
      characteristics, antenatal diagnosis, presence of associated anomalies, method of
      surgical treatment, postoperative complications, number of hospital stay days and
      survival rate were analysed. RESULTS: Most demographic data and associated
      malformation rate in the study patients are in agreement with the data in the
      literature, except for prenatal diagnosis rate (16.7% vs 68- 88%), rapid hospital
      arrival and surgery (6.8 vs 4.3 hours), and the worst, the high rate of
      infections (68.5%) and hence mortality rate (63% vs. 6-7%). CONCLUSIONS: Although
      the therapeutic approach in our clinic complies with the international trend, the
      mortality rate is still very high, its main cause in the study group proving to
      be prolonged sepsis and multiple organ failure, probably favored by the low rate
      of antenatal diagnosis leading to delay in the appropriate surgical management.

PMID- 23958096
TI  - Transarterial embolization of renal vascular lesions after percutaneous
      nephrolithotomy.
AB  - INTRODUCTION: Percutaneous nephrolithotomy (PCNL) represents a safe and efficient
      procedure in the surgical management of renal lithiasis. Nevertheless, surgeons
      have to face specific complications during and after the procedure, hemorrhage
      being one of the most common. In most cases the injuries are self-limited and do
      not need a surgical intervention. Renal arteriography with selective angiographic
      embolization is needed in patients with massive hemorrhage or continuous
      hematuria. Our objective was to evaluate the effectiveness of percutaneous
      transarterial embolization for the treatment of renal arterial post-PCNL
      bleeding. MATERIAL AND METHOD: This retrospective study was performed between
      March 2007 and October 2012 and included 22 patients who had undergone renal
      embolization due to significant post-PCNL renal artery bleeding. The site,
      number, and type of bleeding lesions, and the result of the embolization
      procedure were recorded. We report on the incidence, treatment, radiological and
      clinical results of these serious vascular injuries at our institution. RESULTS:
      Our study has included a large group of patients, the 95.45% angiographic success
      rate confirming that percutaneous transcatheter embolization is a valuable
      treatment for most renal vascular injuries. Renal angiography revealed
      pseudoaneurysm in 15 patients, arteriovenous fistula in 5 and arterial laceration
      in 2 patients. Significant risk factors on univariate analysis for severe
      hematuria requiring superselective angiography were multiple staghorn calculi,
      upper calix puncture and history of pyelonephritis. The severity of the hematuria
      after PCNL is influenced by many factors, including mean stone size and mean
      operative time and is correlated with duration of hospitalization and mean
      hemoglobin drop. CONCLUSIONS: Percutaneous transarterial embolization of the
      injured vessel is an effective, minimally invasive and relatively easy procedure
      in experienced centers, with high rate of success and immediate benefits, thus
      saving the patient from the morbidity that results from severe renal bleeding.

PMID- 23958097
TI  - Age dependent influence of external temperature on the pathogenesis of idiopathic
      lower extremity deep vein thrombosis.
AB  - AIM: The aim of the present study was to investigate the relationship between the
      incidence of idiopathic lower extremity deep vein thrombosis (DVT), age, location
      of the thrombus, and changes of temperature. MATERIAL AND METHOD: During the two
      year period between May 2009 and April 2011, inclusive, 124 consecutive patients
      were diagnosed as having idiopathic lower extremity DVT at the Vascular Surgery
      Clinic, Clinical Center of Nis, Serbia. RESULTS: In patients younger than 45
      years, the increase in average daily temperature with 1 degree C 7 days before
      the event took place was associated (p 0.05) with a decrease of the risk of
      occurrence of idiopathic DVT of the lower limbs of 3.6% (0.4 6.7%) as well as DVT
      above the knees (p 0.01) of 4.7 % (1.3 8.0%). In patients of the age of 45 years
      and over the age of 45 years the increase of average daily temperature with 1
      degree C 7 days before the event took place was associated (p 0.01) with the
      increase of the risk of occurrence of DVT below the knees of 9.4% (3.3 15.9%).
      CONCLUSION: According to the results of this study, one can conclude that the
      influence of external temperature change on DVT incidence and location is based
      on age.

PMID- 23958098
TI  - Nutritional risk screening and prevalence of malnutrition on admission to
      gastroenterology departments: a multicentric study.
AB  - BACKGROUND AND AIMS: There is little awareness and a lack of data on the
      prevalence of hospital malnutrition in gastro-enterology departments. Since part
      of these patients are referred for surgical treatment and poor nutritional status
      is a known risk factor for perioperative morbidity, we conducted a prospective
      study aimed to screen for the nutritional risk and assess the prevalence and risk
      factors of malnutrition in gastro-enterology departments in Romania. METHODS: We
      included patients consecutively admitted to 8 gastroenterology units over a
      period of three months in our study. Nutritional risk was evaluated using NRS
      2002. Malnutrition was defined using BMI ( 20 kg m2) or and 10% weight loss in
      the last six months. RESULTS: 3198 patients were evaluated, 51.6% males and 48.4%
      females, with the mean age of 54.5 A+- 14.3 years. Overall percentage of patients
      at nutritional risk was 17.1%, with the highest risk for patients with advanced
      liver diseases (49.8%), oncologic (31.3%), inflammatory bowel diseases (20.2%),
      and pancreatic diseases (18.9%). The overall prevalence of malnutrition was of
      20.4%, higher for advanced liver diseases (39.4%), inflammatory bowed diseases
      (30.6%), oncologic (26.8%) and pancreatic diseases (23%). Independent risk
      factors for malnutrition were younger age (p 0.0001), female gender (p 0.0001), a
      higher (A >= 3) NRS (p 0.0001), presence of neoplasm (p 0.0001), of advanced
      liver disease (p=0.0003) and a reduction of 25% of dietary intake (p 0.0001).
      CONCLUSIONS: One in five patients admitted to gastroenterology units could
      benefit from prompt nutritional intervention. Correction of nutritional status is
      mandatory before any surgical procedure. Emphasis on nutritional evaluation at
      admission and beginning of nutritional therapy where needed are particularly
      required in patients with advanced liver diseases, digestive neoplasms,
      inflammatory bowel diseases and pancreatic diseases. ABBREVIATIONS: NRS=
      nutritional risk score, BMI = body mass index, IBD = inflammatory bowel diseases.

PMID- 23958099
TI  - Experimental liver transplantation on pigs -- technical considerations.
AB  - The purpose was to improve and refine our technique for orthotopic liver
      transplantation. MATERIAL AND METHOD: Experimental interventions were performed
      on pigs, 26 pairs. Orthotopic transplantation was performed after lavage of the
      donor pig liver by pressure gradient and transplantation was performed using
      portocavo- jugular shunt and veno-venous, arterio-arterial and choledocho
      choledochal sutures in end-to-end manner. RESULTS: Immediate survival was 88.46%.
      CONCLUSIONS: Experimental transplant activity on pigs is of real value,
      contributing to a faster learning curve and at the same time improving handling,
      increasing the efficiency of sutures, as well as anesthetic and surgical team
      building.

PMID- 23958100
TI  - Living donor liver transplantation with dual grafts -- a case report.
AB  - BACKGROUND: Living donor liver transplantation (LDLT) exposes to risks both the
      donor, due to a potential small residual liver volume, and the recipient, who
      faces the risk of small-for-size graft syndrome. In order to overcome these
      drawbacks, liver grafts from two different donors can be used. This paper
      presents a case of dual graft LDLT using a right hemiliver and a left lateral
      section from related donors. CASE PRESENTATION: A 14-year old female diagnosed
      with chronic hepatic failure due to Wilson's disease with Model-for-End- Stage
      Liver-Disease score of 25, underwent a dual graft LDLT, receiving a right
      hemiliver with a reconstructed middle hepatic vein from her sister, and a left
      lateral section from her mother. None of the grafts complied with a satisfactory
      graft-to-recipient weight ratio (GRWR), if they would have been independently
      transplanted. The combined GRWR was 1.10. The donors and the recipient have been
      followed-up for over 1 year. RESULTS: The donors had no postoperative
      complications. The donors and the recipient were discharged 8 and 19 days after
      surgery, respectively. After 12-month follow-up, both donors and the recipient
      were alive, with normal graft function. CONCLUSION: Dual graft LDLT can be a
      feasible solution to overcome the risk of small-for-size graft syndrome.
      ABBREVIATIONS: BSA = body surface area, GRWR = graft-to-recipient weight ratio,
      GV SLV = recipient standard liver volume, HA = hepatic artery, HD = hepatic duct,
      HV = hepatic vein, LDLT = Living donor liver transplantation, LL = left lobe, LLS
      = left lateral section, MELD = Model for End-Stage Liver Disease, POD =
      postoperative day, PV = portal vein, RL = right lobe, SFS = small-for-size graft,
      SLV = standard liver volume, WD = Wilson's disease.

PMID- 23958101
TI  - First heart transplantation in a small child in Romania.
AB  - Heart transplantation is a life-saving procedure for irreducible heart failure in
      children as in adults. Worldwide there is a great amount of experience with this
      procedure, while Romania is only at the beginning. The authors are presenting the
      experience concerning the first small child heart transplantation in Romania,
      underlining the pre-operative and posttransplantation experience. The patient, a
      3 year-old girl, diagnosed with class IV NYHA functional classification
      congestive heart failure secondary to an idiopathic dilated cardiomyopathy, has
      received an isogroup isoRh donor heart on the 14th of January 2011. The operative
      technique used was an orthotopic bicaval technique. In-hospital postoperative
      evolution was favourable, the child receiving triple immunosuppressive therapy
      and prophylaxis therapy against cytomegalovirus, fungi, and pneumocystis carinii
      bacteria. Myocardial biopsy performed 1 month after transplantation showed no
      signs of rejection. The child is in good health at 31 months (2 years, 8 months)
      after the transplantation. Heart transplantation in children is the result of
      teamwork, while the procedure can be performed with low mortality and morbidity
      in centers with large experience in heart transplantation and pediatric
      cardiovascular surgery. 

PMID- 23958102
TI  - Breast cancer. Screening criteria.
AB  - Breast cancer is the most frequent type of neoplastic disease in women, amounting
      to approximately 26% of all annually diagnosed cancers, and representing the
      second leading cause of female death after pulmonary cancer. Although the
      prognosis of the disease has improved in recent years, an important number of
      patients will suffer an evolution of the disease and will die due to this
      malignancy, which remains resistant to various cytostatic drugs, this being the
      main cause for therapeutic failure in over 90% of patients with a neoplastic
      development at this level. As a genic evaluation of the resistance to
      chemotherapy is difficult to obtain under the current clinical practice
      conditions, we desired to follow a series of parameters which were easy to
      evaluate, and which could be correlated with resistance to chemotherapy. Further
      on, we shall report a clinical case of a patient presenting with chemotherapy
      resistant breast cancer and unfavourable prognostic factors, in which we
      determined the biochemical parameters for oxidative stress (serum monoaldehyde a
      marker of lipid peroxidase, serum ceruloplasmin whose activation stimulates an
      overproduction of reactive species of oxygen, plasmatic albumin thiol groups
      important components of antioxidant defence, total serum antioxidants which
      measure the ability of the plasma to resist in face of the effects of reactive
      species of oxygen), correlated with an apoptosis evaluation (scheduled cellular
      death) performed on fresh tumoral tissue.Histopathological, immunohistochemical
      and flowcytometry data correlated. Even if the results obtained indicate a high
      oxidative stress status and a diminished capacity of endogenous antioxidant
      defence, it appears that this oxidative stress alone was not potent enough to
      induce the desired tumoral cytotoxicity.

PMID- 23958103
TI  - Arterio-venous fistula using nonpenetrating titanium clips (VCS).
AB  - Vascular access in haemodialysis is still accompanied by a high morbidity rate.
      Neointimal hyperplasia due to thrombosis is one of the main causes of vascular
      access failure. The purpose of this paper is to present the use of non
      penetrating titanium clips (VCS) for the creation of an arteriovenous fistula and
      its outcome. MATERIALS AND METHODS: A male patient, 47 years old, with end-stage
      renal disease - ESRD - (2005) was addressed to our service, for a vascular access
      reintervention, after a failed forearm radio-cephalic fistula performed 3 months
      before. In January 2007, an arteriovenous fistula between the brachial artery and
      the median cubital vein using non-penetrating titanium clips (Anastoclip VCS) was
      created. RESULTS: The vascular anastomosis was performed in 17 min. After
      unclamping the artery, a solid pulse and consistent thrill were obtained at the
      level of the cubital fossa. The postoperative course was uneventful. The
      arteriovenous fistula remains functional 60 months post-surgery. CONCLUSIONS: The
      Anastoclip VCS system is versatile, safe to manipulate and enables fast
      anastomosis. Arteriovenous anastomosis performed with non-penetrating clips may
      be a solution with the potential to reduce postoperative complications and extend
      arteriovenous fistula patency in ESRD.

PMID- 23958104
TI  - A giant primary thyroid fibrosarcoma in an octogenarian.
AB  - We present an 89-year-old patient who was suffering from severe dyspnoea and mild
      dysphagia due to tracheal and esophagus compression by a giant goitre. The
      patient was euthyreotic. A total thyroidectomy was successfully performed. The
      pathology examination revealed fibrosarcoma G1, which is an extremely rare tumor
      of the thyroid. 

PMID- 23958105
TI  - E-NOTES transumbilical laparoscopic appendectomy.
AB  - We present a case of laparoscopic transumbilical single incision appendectomy. A
      17-year-old patient with an insidious onset of symptoms 4 months ago by diffuse
      abdominal pain that later was localized in the right iliac fossa accompanied by
      loss of appetite, nausea and vomiting. Following clinical examination and
      abdominal ultrasound, she was diagnosed with chronic appendicitis and surgical
      treatment was recommended. Pneumoperitoneum was performed under general
      anesthesia. Three trocars of 5 mm diameter were inserted through a single
      umbilical incision of 10 mm length into the peritoneal cavity. The exploration
      has revealed a swollen appendix. After transsection of the mesoappendix with
      LigaSure forceps, two Roeder knots were placed at on the base of the appendix.
      Intervention duration was 60 minutes. Postoperative course was favorable. Patient
      assessment within 2 months after discharge showed disappearance of symptoms and
      the postoperative scar hidden in the umbilical scar. 

PMID- 23958106
TI  - Total gastrectomy performed in emergency conditions for gastric necrosis due to
      acute gastric dilatation.
AB  - Acute massive gastric dilatation is a rare event, with a pathogenesis still
      debated. Acute massive gastric dilatation invariably leads to necrosis and
      perforation. We present the case of a 50 year-old woman, admitted in emergency
      conditions with circulatory collapse and abdominal distension with the onset 12
      hours prior to presentation. An emergency laparotomy was performed revealing a
      stomach occupying the entire abdominal cavity with necrosis and anterior pyloric
      perforation. The operation consisted in total gastrectomy with stapled Roux-en-Y
      anastomosis. The postoperative evolution was simple, without complications. Acute
      massive gastric dilatation is a severe, lethal condition with multiple etiologic
      factors like anorexia nervosa, trauma, diabetes, postoperative period in
      abdominal surgery, electrolyte disturbances. In most cases emergency surgical
      treatment is necessary, dictated by gastric necrosis or perforation. Conservative
      treatment may represent an option if it is early instituted. 

PMID- 23958107
TI  - Multiple benign symmetric lipomatosis -- a differential diagnosis of obesity.
AB  - Benign symmetrical lipomatosis (BSL), or Madelung's disease, is a rare disease
      characterized by the progressive growth of diffuse, painless, non-enveloped
      symmetric lipomas. The etiology of this disease remains unknown, although it was
      associated in the medical literature with alcohol and nicotine abuse, metabolic
      disorders and a number of malignancies. It is assumed that there is a genetic
      predisposition for this affliction. The management in such cases is surgical
      removal of the lipomas, most times in several sessions, but this is often
      followed by relapse. However, surgical removal of the lipomas can provide
      satisfactory patient functionality and cosmetic results. The differential
      diagnosis is made with morbid obesity, Cushing syndrome, angiolipomatosis,
      encapsulated lipomas, neurofibromatosis, myxoid liposarcoma, lymphoma, salivary
      gland disease, Frolich and lipomatosis syndrome in patients infected with HIV.
      The current paper reports the case of a 55 year-old man, who presented with
      several large lipomatous masses, arranged symmetrically on the front and back of
      the trunk, and several smaller lipomas in the upper and lower limbs. Treatment
      consisted of resection of these lipomas in several sessions, without recurrence
      at one year after the last operation.

PMID- 23958108
TI  - Solitary ganglioneuromatosis of the descending colon, presenting as giant
      retroperitoneal tumour.
AB  - Ganglioneuroma (GN) is a benign neoplasia of the autonomous nervous system,
      colonic GN is uncommon in adults. There are three subgroups: polypoid GN,
      ganglioneuromatous polyposis and diffuse ganglioneuromatosis. Ganglioneuromatosis
      is highly-associated to neurofibromatosis type 1 (NF1) and multiple endocrine
      neoplasia type 2b (MEN2B). A 68-year-old female, with a discrete retarded
      emission of stools, was admitted for a large tumor in the left flank; CT scan,
      urography and barium enema demonstrated a large retroperitoneal mass, presumed as
      sarcoma. Open surgery discovered a 16 10 11 cm solid and encapsulated tumor,
      attached to the retroperitoneal descending colon, with no macroscopic mucosal
      involvement; the pathologic diagnosis of the resected specimen (en-bloc
      tumorectomy with limited colectomy) was intramural colonic ganglio-neuromatosis.
      Anamnesis, physical examination and complete endoscopic explorations showed no
      evidence of personal bearing or familial aggregation of genetic syndromes. In
      adults, association of transmural ganglioneuromatosis to NF1 or MEN2B is not
      mandatory; presentation often mimics obstructive carcinoma and positive diagnosis
      is provided by pathological examination of the resected specimen. In this
      peculiar case, the loose tissue of the retroperitoneal space favoured a slow
      development of intramural ganglioneuromatosis, presenting as a gigantic
      retroperitoneal mass with no radiological evidence of its colonic origin. 

PMID- 23958110
TI  - Explaining lower rates of sexual abuse in China.
AB  - Accumulating research suggests that rates of child sexual abuse are comparatively
      low in China. This commentary is an effort to evaluate whether it reflects a true
      lower prevalence or alternatively the effect of inhibited disclosure by victims.
      We conclude that while some estimates have almost certainly been affected by
      inhibited disclosure, the overall magnitude of the contrast between Chinese and
      international rates, particularly for girls, and its consistency with other
      indicators do suggest a true lower prevalence, although the evidence is
      equivocal. We discuss some factors that could account for such lower rates
      including Confucian family values, definitions of masculinity and a collectivist
      culture that may be protective. 

PMID- 23958109
TI  - The TARGET cohort study protocol: a prospective primary care cohort study to
      derive and validate a clinical prediction rule to improve the targeting of
      antibiotics in children with respiratory tract illnesses.
AB  - BACKGROUND: Children with respiratory tract infections are the single most
      frequent patient group to make use of primary care health care resources. The use
      of antibiotics remains highly prevalent in young children, but can lead to
      antimicrobial resistance as well as reinforcing the idea that parents should re
      consult for similar symptoms. One of the main drivers of indiscriminate
      antimicrobial use is the lack of evidence for, and therefore uncertainty
      regarding, which children are at risk of poor outcome. This paper describes the
      protocol for the TARGET cohort study, which aims to derive and validate a
      clinical prediction rule to identify children presenting to primary care with
      respiratory tract infections who are at risk of hospitalisation. METHODS/DESIGN:
      The TARGET cohort study is a large, multicentre prospective observational study
      aiming to recruit 8,300 children aged >=3 months and <16 years presenting to
      primary care with a cough and respiratory tract infection symptoms from 4 study
      centres (Bristol, London, Oxford and Southampton). Following informed consent,
      symptoms, signs and demographics will be measured. In around a quarter of
      children from the Bristol centre, a single sweep, dual bacterial-viral throat
      swab will be taken and parents asked to complete a symptom diary until the child
      is completely well or for 28 days, whichever is sooner. A review of medical notes
      including clinical history, re-consultation and hospitalisations will be
      undertaken. Multivariable logistic regression will be used to identify the
      independent clinical predictors of hospitalisation as well as the prognostic
      significance of upper respiratory tract microbes. The clinical prediction rule
      will be internally validated using various methods including bootstrapping.
      DISCUSSION: The clinical prediction rule for hospitalisation has the potential to
      help identify a small group of children for hospitalisation and a much larger
      group where hospitalisation is very unlikely and antibiotic prescribing would be
      less warranted. This study will also be the largest natural history study to date
      of children presenting to primary care with acute cough and respiratory tract
      infections, and will provide important information on symptom duration, re
      consultations and the microbiology of the upper respiratory tract.

PMID- 23958111
TI  - Antibodies against gonadotropin-releasing hormone (GnRH) in patients with
      diabetes mellitus is associated with lower body weight and autonomic neuropathy.
AB  - BACKGROUND: Esophageal dysmotility and gastroparesis are common secondary
      complications in patients with diabetes mellitus. Patients with dysmotility
      express antibodies against gonadotropin-releasing hormone (GnRH) in serum. The
      aim of the present study was to scrutinize patients with diabetes mellitus with
      regard to the presence of GnRH antibodies, and to examine associations between
      antibodies and clinical findings. RESULTS: Thirty-nine consecutive patients with
      diabetes mellitus were included in the study after clinical examination and
      examination by esophageal manometry and gastric emptying scintigraphy. Serum was
      analyzed for the presence of antibodies against GnRH using an ELISA, and values
      are expressed as relative units (RU). Two age- and gender-matched healthy
      subjects per each patient served as controls. The prevalence of IgM GnRH
      antibodies in patients was 33% compared to 14% in controls (p = 0.027), with a
      higher antibody titer; 1.2 (0.6-5.0) and 0.2 (0.1-0.3) RU, respectively (p =
      0.000). The expression of IgG antibodies was 15% in patients and none in controls
      (p = 0.000). Lower body mass index was associated with the presence of IgM
      antibodies (OR = 0.835, 95% CI = 0.699-0.998), and autonomic neuropathy with the
      presence IgG antibodies (OR = 9.000, 95% CI = 1.327-61.025). Esophageal
      dysmotility (69%) or gastroparesis (18%) were not associated with the presence of
      IgM antibodies (OR = 0.589, 95% CI = 0.143-2.424 and OR = 3.407, 95% CI = 0.633
      18.350, respectively). Neither was esophageal dysmotility associated with IgG
      antibodies (OR = 2.500, 95% CI = 0.259-24.096). CONCLUSIONS: Antibodies against
      GnRH are more common in patients with diabetes mellitus compared with healthy
      controls. IgM antibodies are associated with lower body mass index and IgG
      antibodies are associated with autonomic neuropathy.

PMID- 23958113
TI  - Intranasal exposure to amorphous nanosilica particles could activate intrinsic
      coagulation cascade and platelets in mice.
AB  - BACKGROUND: Nanomaterials with particle sizes <100 nm have been already applied
      in various applications such as cosmetics, medicines, and foods. Therefore,
      ensuring the safety of nanomaterials is becoming increasingly important. Here we
      examined the localization and biological responses of intranasally administered
      amorphous nanosilica particles in mice, focusing on the coagulation system.
      METHODS: We used nanosilica particles with diameters of 30, 70, or 100 nm (nSP30,
      nSP70, or nSP100 respectively), and conventional microscale silica particles with
      diameters of 300 or 1000 nm (mSP300 or mSP1000, respectively). BALB/c mice were
      intranasally exposed to nSP30, nSP70, nSP100, mSP300, or mSP1000 at
      concentrations of 500 MUg/mouse for 7 days. After 24 hours of last
      administration, we performed the in vivo transmission electron microscopy
      analysis, hematological examination and coagulation tests. RESULTS: In vivo
      transmission electron microscopy analysis showed that nanosilica particles with a
      diameter <100 nm were absorbed through the nasal cavity and were distributed into
      liver and brain. Hematological examination and coagulation tests showed that
      platelet counts decreased and that the activated partial thromboplastin time was
      prolonged in nSP30 or nSP70-treated groups of mice, indicating that nanosilica
      particles might have activated a coagulation cascade. In addition, in in vitro
      activation tests of human plasma, nanosilica particles had greater potential than
      did conventional microscale silica particles to activate coagulation factor XII.
      In nanosilica-particle-treated groups, the levels of soluble CD40 ligand, and von
      Willebrand factor which are involved in stimulating platelets tended to slightly
      increase with decreasing particle size. CONCLUSIONS: These results suggest that
      intranasally administered nanosilica particles with diameters of 30 and 70 nm
      could induce abnormal activation of the coagulation system through the activation
      of an intrinsic coagulation cascade. This study provides information to advance
      the development of safe and effective nanosilica particles.

PMID- 23958114
TI  - Differential gene expression in peripheral blood T cells from patients with
      psoriasis, lichen planus, and atopic dermatitis.
AB  - BACKGROUND: Psoriasis, lichen planus (LP), and atopic dermatitis (AD) are common
      chronic inflammatory skin diseases mediated by immune responses. OBJECTIVE: We
      used RNA sequencing to investigate messenger RNA expression patterns in
      peripheral T cells of Chinese patients with psoriasis, LP, or AD and of healthy
      individuals. METHODS: After peripheral T-cell proliferation, messenger RNA
      expression patterns were investigated by RNA sequencing, and 6 randomly selected
      genes were verified by real-time reverse transcriptase polymerase chain reaction.
      RESULTS: Six genes were down-regulated and 33 were up-regulated in these
      diseases. Gene ontology analysis revealed enrichment of genes involved in
      positive regulation of T-cell activation. Regulation of nuclear premessenger RNA
      domain containing 1B (RPRD1B) expression was enhanced in psoriasis. LIMITATIONS:
      The role of hereditary factors in RPRD1B expression in T cells was not
      considered. Immunomodulators (thymopeptide, levamisole, BCG polysaccharide,
      nucleic acid injection, and transfer factor) were previously given to patients
      with psoriasis and LP, but not to patients with AD; the effects of these
      immunomodulators on gene expression is uncertain. CONCLUSION: RPRD1B may be
      involved in T-cell activation in our Chinese psoriatic cohort, and may play a
      role in stimulating epidermal hyperproliferation.

PMID- 23958115
TI  - A year-long caregiver training program improves cognition in preschool Ugandan
      children with human immunodeficiency virus.
AB  - OBJECTIVE: To evaluate mediational intervention for sensitizing caregivers
      (MISC). MISC biweekly caregiver training significantly enhanced child development
      compared with biweekly training on health and nutrition (active control) and to
      evaluate whether MISC training improved the emotional well-being of the
      caregivers compared with controls. STUDY DESIGN: Sixty of 120 rural Ugandan
      preschool child/caregiver dyads with HIV were assigned by randomized clusters to
      biweekly MISC training, alternating between home and clinic for 1 year. Control
      dyads received a health and nutrition curriculum. Children were evaluated at
      baseline, 6 months, and 1 year with the Mullen Early Learning Scales and the
      Color-Object Association Test for memory. Caldwell Home Observation for
      Measurement of the Environment and videotaped child/caregiver MISC interactions
      also were evaluated. Caregivers were evaluated for depression and anxiety with
      the Hopkins Symptoms Checklist. RESULTS: Between-group repeated-measures ANCOVA
      comparisons were made with age, sex, CD4 levels, viral load, material
      socioeconomic status, physical development, and highly active anti-retroviral
      therapy treatment status as covariates. The children given MISC had significantly
      greater gains compared with controls on the Mullen Visual Reception scale (visual
      spatial memory) and on Color-Object Association Test memory. MISC caregivers
      significantly improved on Caldwell Home Observation for Measurement of the
      Environment scale and total frequency of MISC videotaped interactions. MISC
      caregivers also were less depressed. Mortality was less for children given MISC
      compared with controls during the training year. CONCLUSIONS: MISC was effective
      in teaching Ugandan caregivers to enhance their children's cognitive development
      through practical and sustainable techniques applied during daily interactions in
      the home.

PMID- 23958117
TI  - [Major issues and challenges of influenza prevention and control in China].

PMID- 23958118
TI  - [Influenza epidemic situation and control countermeasures in China in 2013].

PMID- 23958116
TI  - Perceived social-ecological factors associated with fruit and vegetable
      purchasing, preparation, and consumption among young adults.
AB  - Most young adults do not consume recommended levels of fruits and vegetables
      (F/V), and interventions to increase F/V-related behaviors among this
      understudied population are needed. Therefore, it is important to identify
      correlates of F/V intake among young adults to guide intervention development.
      This cross-sectional study used data from an online survey to identify factors
      related to young adults' F/V purchasing, preparation, and consumption, and to
      explore between-factor relationships using mediation analysis. In 2010, 1,201
      college students in Minnesota completed questionnaires assessing F/V behaviors as
      well as perceptions of F/V-related individual, social, and environmental factors.
      Factor analysis identified questionnaire items assessing similar constructs.
      Seven factors were identified (personal barriers, F/V knowledge, family, friends,
      neighborhood, access barriers, and campus) and evaluated for relationships with
      F/V purchasing, preparation, and consumption using linear regression. Results
      revealed that perceived personal barriers (eg, lacking cooking skills) were
      inversely related to all F/V outcomes. Perception that family and friends eat
      healthfully and neighborhood access to F/V were positively related to all
      outcomes. Individual-, social-, and environment-level perceptions were related to
      purchasing, preparation, and consumption, and the effects of these factors were
      similar when accounting for mediated effects. Factors at all three levels and the
      ways in which these various factors operate together may be important to consider
      in future efforts to improve F/V behaviors among young adults. 

PMID- 23958119
TI  - [Enhancement control of salmonella prevalence in boiler chicken].

PMID- 23958120
TI  - [Prevalence reasons and control measure analysis of super-resistant bacteria in
      China].

PMID- 23958121
TI  - [Epidemic situation and the prevention strategy of the work-related
      musculoskeletal disorders].

PMID- 23958122
TI  - [Analysis of genetic variation of hemagglutinin and three internal genes of
      influenza B virus isolated in Zhejiang province from 1999 to 2012].
AB  - OBJECTIVE: To explore the characteristics of the genetic variation of
      hemagglutinin( HA) and three internal genes coding for the nucleoprotein ( NP) ,
      matrix protein ( M) and nonstructural protein ( NS) of influenza B virus.
      METHODS: A total of 31 strains of influenza B virus were isolated in Zhejiang
      province from 1999 to 2012, and then were amplified and sequenced the genes of
      HAl , NP, M and NS. The phylogenetic tree was constructed, the nucleotide
      substitution rate of the above individual gene was estimated and the variation
      sites of amino acids were analyzed. RESULTS: The 31 isolated strains of influenza
      B virus were divided into two distinct lineages Victoria and Yamagata in the
      phylogenetic tree of HAl gene,represented by B/Victoria/2/87 and
      B/Yamagata/16/88. Phylogenetic analysis of the NP gene showed that the NP gene of
      Victoria-like influenza B strains which were isolated after 2010 was highly
      homologous with Yamagata-like isolates, and thereby they were found to be on the
      same branch of the phylogenetic tree of the NP gene. Nucleotide substitution
      rates of HAl , NP, M and NS genes were estimated to be 2. 29 x 10 -3 ,1. 39 X 10
      3 ,1. 78 X 10-3 ,1. 30 X 10-3 /site per year, respectively. Variations of amino
      acid of HAl domain of Victoria-like isolates mainly included K48E ,L58P
      ,N75K,K80R,K129N/S,N165K,S172P ,Sl97N/D and A202V; while those in Yamagata-like
      isolates were R48K, S1501, N166Y, N203S, G230D and D233N. Determined amino acid
      sequences of NP of Victoria-like influenza B isolates were similar to Yamagata
      like isolates after 2010 and variations happened on four characteristic amino
      acid sites, naming A60D, I233V, N513S and V5341, compared with previous Victoria
      like influenza B isolates. CONCLUSION: Significant variation was found among
      influenza B strains isolated in Zhejiang province from 1999 to 2012. The surface
      HAl gene evolved more rapidly than internal genes. Gene reassortment and gene
      mutation were the main evolutionary mechanism of influenza B virus.

PMID- 23958123
TI  - [Epidemiological characteristics of influenza virus and respiratory syncytial
      virus among children in Wuhan area from 2008 to 2012].
AB  - OBJECTIVE: To investigate the infection status and epidemiological
      characteristics of influenza virus and respiratory syncytial virus (RSV) in
      influenza-like illness (ILI) of children ( <= 14 years) in Wuhan area from 2008
      to 2012. METHODS: A total of 2854 cases of ILI patients ( <= 14 years) in a
      hospital of Wuhan were recruited in the study from July 2008 to June 2012. The
      sample of pharyngeal swab was collected from each patient, to extract the virus
      nucleic acids. Real-time fluorescent quantitation reverse transcription PCR (RT
      PCR) method was applied to detect the subtypes of influenza virus and RSV, and
      then analyzed the time and age characteristics. RESULTS: Out of the 2854 cases,
      758 (26.6%) were positive for influenza virus,including 547 (19.2%) influenza A
      virus positive samples and 211 (7.4%) influenza B virus positive samples.
      Usually, there were two peaks present in the annual curve of influenza virus,
      namely summer peak and winter/spring peak. The positive rate of influenza virus
      in 6-14 years old children (48.0%, 275/573) was significantly higher than that in
      3-5 years old children (26.6%, 213/801) and that under 3 years old children
      (18.3%, 270/1480). The difference showed statistical significance (chi(2) =
      187.432, P < 0.01). A total of 219 (7.7%) cases were positive for RSV,including
      108 RSV-A positive samples and 112 RSV-B positive samples (1 co-infection). The
      epidemic of RSV showed an obvious seasonal pattern with peaks in autumn,winter
      and spring,which accounted for 96.8% (212/219) of all the cases; however, the
      annual incidence of RSV fluctuated greatly. The predominant subtype shifted every
      2 years. RSV-B predominated during September 2008 and May 2009, December 2009 and
      March 2010, accounting for 76.6% (36/47) and 96.9% (62/64) respectively. RSV-A
      predominated during November 2010 and March 2011, September 2011 and April 2012,
      accounting for 92.5% (37/40) and 100.0% (48/48) respectively. With the increase
      of the age, the positive rate of RSV-A and RSV-B decreased gradually (RSV-A:
      chi(2) = 36.223, P < 0.01; RSV-B: chi(2) = 36.281, P < 0.01). The positive rates
      of RSV-A in children < 1,1,2,3,4,5-9 and 10-14 years old were 7.0% (26/373), 5.9%
      (39/662), 4.0% (18/445), 3.2% (13/406), 1.3% (3/236), 1.4% (7/517) and 0.9%
      (2/215) respectively; while, the positive rates of RSV-B in each age group were
      6.4% (24/373), 6.0% (40/662), 4.5% (20/445), 4.4% (18/406), 1.3% (3/236), 1.0%
      (5/517) and 0.9% (2/215) respectively. The children aged 0-3 years old were more
      susceptible for RSV infection,accounting for 90.0% (197/219) of the total
      positive samples. During the outbreak of influenza A H1N1 in November 2009, the
      positive rate of RSW was 3.0% (3/100), lower than that in the same month of 2008,
      2010 and 2011,which were separately 18.2% (6/33), 10.8% (10/93) and 10.0% (4/40).
      The difference showed statistical significance (chi(2) = 8.450, P < 0.05). During
      the outbreak of influenza A (H1N1) in January 2011,the positive rate of RSV was
      5.7% (3/53), lower than those in the same month of 2009, 2010 and 2012, which was
      separately 21.7% (5/23), 28.6% (22/77) and 16.0% (8/50). The difference showed
      statistical significance (chi(2) = 11.233,P < 0.05). During the period of less
      influenza happened in September 2011, the RSV positive rate was 25.0% (10/40),
      higher than those in the same month of 2008, 2009 and 2010, which was separately
      11.4% (4/35), 1.7% (2/118) and 0.0% (0/109). The difference showed statistical
      significance (chi(2) = 32.521, P < 0.01). CONCLUSION: Both influenza virus and
      RSV were important etiological agents of ILI of children in Wuhan. The
      characteristics of seasonal and age distributions of the two viruses were notably
      different; meanwhile, a certain inhibitional effect of influenza virus on RSV
      could be observed.

PMID- 23958124
TI  - [Analysis on the whole genome of the influenza H1N1 virus of the mild and severe
      cases in Beijing in 2009].
AB  - OBJECTIVE: To explore the characteristics of the whole genome of the influenza
      H1N1 virus of the mild and severe cases in Beijing. METHODS: A total of 21
      samples of throat swabs were collected from surveillance-designated hospitals
      between June and December in 2009, including 10 severe cases (4 death cases) and
      11 mild cases. RNA of the virus were extracted,and the amplified primers of the
      whole genome were designed.Reverse transcription and PCR were performed to the
      RNA and then the PCR product was sequenced by software to analyze the evolution
      of the viral genes and the variation of the amino acids. RESULTS: Compared with
      the reference vaccine strain A/California/07/2009 (H1N1), the genetic nucleotide
      homology in the eight segments of the pandemic H1N1 virus in Beijing in 2009 was
      higher than 99%, without significant variation. Among them,the genetic distance
      of hemagglutinin (HA), neuraminidase (NA) and nucleoprotein (NP) was
      comparatively far, separately 0.0050, 0.0040 and 0.0040.The gene of HA, P83S, the
      gene of NA, N248D, the gene of polymerase (PA), P224S and the gene of NP, V100I
      and L122Q were found to mutate in all the samples. Genes of HA, NA, NP, PA, PB 2
      and nonstructural protein (NS1) in severe cases showed obviously clustered
      evolution. The mutation of gene S128P and S203T of HA, gene R269R and D547E of
      PA, gene T588I of PB 2 and gene I123V of NS mainly happened in severe cases,
      separately counting 6, 9, 6, 7, 9 and 6 cases. The relevance between the mutation
      happened in S203T of HA, R269K and D547E of PA and the severeness of the cases
      showed statistical significance (P < 0.05). The mutations of HA gene were mainly
      on the Ca and Cb antigene domains. No drug resistant mutation was found on NA
      gene but happened on matrix protein 2 (M2 gene). None of the mutations were found
      on the virulence related genes. CONCLUSION: A high homology was found between the
      pandemic H1N1 virus in Beijing in 2009 and the reference vaccine strain
      A/California/07/2009(H1N1). Mutational sites related with the severe and fatal
      cases were found, but not the virulence related mutation.

PMID- 23958125
TI  - [Molecular investigation of a possible case of HIV transmission after a blood
      transfusion].
AB  - OBJECTIVE: A molecular technique based on quasispecies analysis for tracing
      postexposure HIV transmission was applied in an investigation of a possible case
      of HIV transmission after blood transfusion. METHODS: Sixteen plasma specimens
      were collected from 3 HIV infections (T1-T3) involved in a possible HIV
      transmission chain and 13 HIV/AIDS (C1-C13) controls. The RNAs were extracted and
      then amplified by RT-PCR, the PCR products were cloned and sequenced.BioEdit
      6.0.7 and MEGA 4.0 software were used to analyze gene sequences, calculate gene
      dispersion ratio and construct phylogenetic tree. RESULTS: The sequences of 13
      specimens were successfully obtained.The HIV strains from T1, T2 and T3 were
      CRF07_BC recombinants, those from 5 out of the 6 controls lived in the same city
      with T2 and T3 were CRF07_BC recombinants as well, while those from 4 controls
      living in the same city with T1 were CRF01_AE recombinants. Compared with the
      clone sequences from T1, the mean gene dispersion ratio of T2 was the least
      (2.0%), followed by C12 (2.8%) , T3 (2.9%) and others. The phylogenetic tree
      showed that all clones from T1, T2, T3 and C12 might cluster together,and implied
      that the direction of HIV transmission was from T3 to T2, and then to T1.
      CONCLUSION: The results support the possible epidemiological clue that HIV was
      transmitted from T3 to T2, and then to T1, indicating that molecular
      epidemiological investigation could provide more direct evidence for tracing
      postexposure HIV transmission.

PMID- 23958126
TI  - [The impact of community-based organizations in HIV testing mobilization among
      men who have sex with men].
AB  - OBJECTIVE: To analyze the impact of efforts of community-based organizations
      (CBO) in HIV testing mobilization and case finding among men who have sex with
      men(MSM). METHODS: Results of HIV testing mobilization among MSM through CBOs in
      15 program areas were collected and compared with corresponding HIV case
      reporting data to demonstrate the contribution of CBO-based HIV testing in HIV
      case finding among MSM from July 2008 to December 2011. Meanwhile,the proportion
      of screened HIV positives who received testing results notification,confirmatory
      test, following up and CD4 cell tests were analyzed and compared with those
      identified in medical institutions. RESULTS: A total of 196 075 HIV tests were
      performed for MSM, as a result of mobilization efforts of CBOs. Cumulatively 7704
      new HIV cases were identified, accounting for 51.7% (7704/14 914) of all newly
      diagnosed HIV cases infected via homosexual sex in the program areas.Among the
      newly diagnosed MSM HIV infections in the program areas,the proportion of
      infections detected through the mobilization of CBOs increased from 35.4%
      (609/1722) in 2008 to 63.7% (2371/3722) in 2010, and 58.3% (3024/5189) in 2011.
      Compared with those identified through medical institutions, newly diagnosed MSM
      infections detected though CBOs testing mobilization have higher rates of
      receiving screening testing results notification (97.3% (4441/4563) vs 92.8% (13
      140/14 153)) , (84.6% (2559/3024) vs 79.8% (5589/7002)) and CD4 cell tests (66.1%
      (1999/3024) vs 52.9% (3705/7002)), and a lower rate of receiving confirmatory
      test (78.6% (3588/4563) vs 85.6% (12 115/14 153)). CONCLUSION: CBOs can take
      their advantages in mobilizing MSM to receive HIV test, and MSM HIV cases
      detected through CBOs have become the main source of MSM HIV case finding in
      program areas.

PMID- 23958127
TI  - [Prevalence and antibiogram distribution of Salmonella isolated from broiler
      production and processing course in four provinces, China].
AB  - OBJECTIVE: To determine the contamination condition of Salmonella in broiler
      breeding and slaughter processing in China and to investigate the distribution of
      antimicrobial resistance profiles. METHODS: Five large-scale broiler holdings and
      fourteen slaughterhouses were chosen to detect Salmonella in Henan, Jiangsu,
      Sichuan and Shandong provinces in 2010. A total of 835 anal swabs and 744 chicken
      carcasses were sampled to compare the difference of Salmonella contamination
      rate.Salmonella isolates were identified by serotyping according to Kauffmann
      White scheme.The antimicrobial susceptibilities of Salmonella isolates were
      determined by broth microdilution method and sixteen antimicrobial agents were
      chosen and examined. RESULTS: In total, Salmonella isolates were recovered in 56
      (6.7%) specimens among 835 collected anal swabs and 122 (16.4%) specimens among
      744 broiler carcasses. Positive rate of Salmonella in broiler carcasses was
      higher than anal swabs (chi(2) = 36.94, P < 0.05). The dominant Salmonella
      serovars isolated from broiler anal swabs were S.enterica serovar Indiana and
      S.enterica serovar Enteritidis, accounting for 58.9% (33/56) and 32.1% (18/56)
      respectively. The prevalent serovars in broiler carcasses were also the two
      serovars and occupied 29.8% (37/124), 32.2% (40/124) respectively. Nearly 95.0%
      (171/180) Salmonella isolates were resistant to at least one antimicrobial, 78.3%
      (141/180) Salmonella strains were multi-drug resistant isolates and 20 (11.1%)
      Salmonella isolates were resistant to 14 antimicrobials. CONCLUSION: Our findings
      indicated that Salmonella contamination was common and serious in commercial
      broiler production and processing course in China. Salmonella contamination rate
      in broiler slaughter processing performance was higher than broiler flocks.
      Additionally, antibiotic resistance of Salmonella was in serious situation.

PMID- 23958128
TI  - [Construction of biofilm formation related mutants in Vibrio parahaemolyticus].
AB  - OBJECTIVE: To construct the mutants of biofilm related genes in Vibrio
      parahaemolyticus and confirm the mutants. METHODS: The homologous upstream and
      downstream flanking fragments of target gene were amplified by using PCR, and the
      fusion homologous fragment was amplified by using the two flanking fragments as
      template. Then the fusion homologous fragment was digested by restriction enzyme
      and cloned into suicide plasmid pDS132. The recombinant plasmid was transferred
      into Vibrio parahaemolyticus RIMD 2210633 through conjugation. The mutants were
      screened and identified by PCR and the phenotype of one mutant was analyzed in
      order to verify that the mutants were constructed successfully. RESULTS: Six
      recombinant plasmids carrying the fusion homologous fragments of genes vbfR, crp,
      hns, swrZ, swrT and cpsR respectively were constructed and identified by PCR. The
      amplification products of 1190, 1128, 1136, 953, 1242 and 1112 bp were obtained
      respectively. The six mutants (DeltavbfR, Deltacrp, Deltahns, DeltaswrZ,
      DeltaswrT and DeltacpsR) were constructed using recombinant plasmids. Verified by
      PCR, the size of amplification products of mutants (1190, 1128, 1136, 953, 1242
      and 1112 bp respectively) was less (610, 739, 421, 542, 427 and 1367 bp
      respectively) than the corresponding positive control. Meanwhile, none of the
      products was amplified using the primers locating on the target gene. One mutant
      Deltahns was selected to test the ability of biofilm formation. The result showed
      that the ability of biofilm formation of mutant Deltahns was increased compared
      with the wild type. CONCLUSION: Six mutants of biofilm related genes in Vibrio
      parahaemolyticus were constructed and tested by molecular and phenotype
      experiment to confirm that the mutants were constructed successfully.

PMID- 23958129
TI  - [Cell death of THP-1 induced by puried Rv3671c protein of tuberculosis and the
      detection of TNF-alpha and IL-1beta in Mycobacterium tuberculosis].
AB  - OBJECTIVE: To assess the response in THP-1 treated with Rv3671c protein in
      Mycobacterium tuberculosis (M.tuberculosis). METHODS: The gene encoding Rv3671c
      protein of M.tuberculosis was cloned into pET-28a vector and then expressed in
      Escherichia coli. The Rv3671c was purified with Ni-NTA affinity and ion exchange
      chromatography. The detection of protein concentration was by Lowry method.THP-1
      cell was stimulated with Rv3671c protein and cells were analyzed by Hochest
      staining under fluorescence microscopy to assay cell death (apoptosis and
      necrosis). TNF-alpha and IL-1beta were detected by ELISA at each stimulating
      time. RESULTS: The Rv3671c protein of M.tuberculosis was successfully expressed
      in Escherichia coli. The purity of recombinant Rv3671c protein was 95%, and the
      protein concentration was up to 0.4 mg/ml. The nucleus of THP-1 was isolated and
      necrosis-like under fluorescence when cells were stimulated by Rv3671c protein.
      The levels of TNF-alpha and IL-1beta in supernatant were 19 000 and 16 500 pg/ml
      respectively, and were significantly higher than control cells with the levels of
      2100 and 3800 pg/ml separately. CONCLUSION: The necrosis of THP-1 cells could be
      stimulated by Rv3671c protein of M.tuberculosis and it was probably associated
      with high cytokines TNF-alpha and IL-1beta levels.

PMID- 23958130
TI  - [Development of a real-time reverse transcriptase PCR assay for detection of
      E119V amino acid change in neuraminidase of influenza A (H3N2) using the TaqMan
      MGB probe].
AB  - OBJECTIVE: To develop a rapid duplex Real-time reverse transcription PCR (rRT
      PCR) method to detect E119V mutation on neuraminidase (NA) of influenza A(H3N2)
      subtype with drug resistance to oseltamivir. METHODS: Twenty-six NA genes of
      influenza A(H3N2) virus between 2000 and 2012 in GenBank database were selected
      as the target genes, and specific TaqMan-MGB probe was designed to target the
      E119V amino acid change in neuraminidase protein. rRT-PCR was then performed and
      evaluated for the sensitivity, specificity and reproducibility using virus with
      E119V mutation and clinical samples. RESULTS: This study described the validation
      of a highly sensitive and specific duplex rRT-PCR for detection of substitutions
      leading to the E119V amino acid change in NA protein of influenza A(H3N2).
      Fluorescence signals could be detected even when diluted a A (H3N2) virus (HA =
      8) into 10(-5) and linear correlation between the logarithm of the viral titer
      with the Ct values was observed. In addition, the assay was highly specific in
      that there was no cross-react with other respiratory viruses, nor did two TaqMan
      MGB probes. E119V substitution in quasispecies with both sensitive and resistant
      viruses could be detected as well. The limit of detection was 5% for quasispecies
      with high concentrations and 50% for quasispecies with low concentrations. The
      average coefficient of variation (CV) for within-run assays was 2.32% and 0.57%
      for H3N2-119E and H3N2-119V primer/probe sets separately, 1.77% and 0.97% for
      average CV of between-run assays, which exhibited good repeatability. Sequence
      analysis of twenty NA genes verified glutamic acid (E) at amino acid site 119,
      which was in consistent with the results from our rRT-PCR method. CONCLUSION: The
      assay developed in this study is highly sensitive and specific, and easy to
      operate; thereby it could be used for identification of A(H3N2) virus with E119V
      amino acid change in NA protein.

PMID- 23958131
TI  - [Quantitative analysis of foodborne salmonella-the study of mini-modified semi
      solid rappaport vassiliadis most probable number method].
AB  - OBJECTIVE: To improve the mini-modified semi solid rappaport vassiliadis most
      probable number (mini-MSRV MPN) method for Salmonella detection. METHODS: Based
      on the mini-MSRV MPN method,Buffered Peptone Water (BPW) was modified as one step
      enrichment medium and Modified Semi Solid Rappaport Vassiliadis (MSRV) medium was
      ameliorated as modified MSRV for Salmonella detection under standard Salmonella
      addition recovery. A total of 154 raw chicken samples, 48 swabs of pheasantry and
      48 poultry dung samples were collected to compare the detection results of
      Salmonella by using improved mini-MSRV MPN, mini-MSRV MPN and regular most
      probable number (MPN) method. RESULTS: Salmonella recovery was < 2.7 MPN/g when
      the standard Salmonella addition was at the concentration of 0.9 CFU/g when the
      mini-MSRV MPN method was employed. If the standard Salmonella addition were at
      9.0 and 90.0 CFU/g, the recoveries of bacteria were 10.1 and 94.0 MPN/g, and the
      average recovery rate was 112% and 104%, respectively. Salmonella detection rate
      of modified mini-MSRV MPN, mini-MSRV MPN and regular MPN method was 18.4%
      (46/250), 5.2% (13/250) and 6.0% (15/250), respectively. The detection rate was
      higher for modified mini-MSRV MPN method than of the other two methods (chi(2)
      values were 19.68 and 17.82, respectively, all P values < 0.05). The detection
      quantity of Salmonella (medians were 21.0, < 2.7 and < 3.0 MPN/g, respectively).
      The quantity detected by modified mini-MSRV MPN method was higher than that of
      the other two methods (both Z values were 5.71, both P values < 0.05).
      CONCLUSION: Modified mini-MSRV MPN method is an accurate method for foodborne
      Salmonella detection.

PMID- 23958132
TI  - [Determination of epichlorohydrin in drinking water by isotope dilution gas
      chromatography-mass spectrometry].
AB  - OBJECTIVE: To establish a method for determination of the epichlorohydrin in
      drinking water by isotope dilution gas chromatography-mass spectrometry (GC-MS).
      METHODS: The internal standard solution D5-epichlorohydrin was added in drinking
      water sample. The epichlorohydrin was firstly collected by active carbon, and the
      adsorbent was then centrifuged at 2739 * g for 10 min to remove water. Finally,
      the epichlorohydrin was desorbed by dipping the active carbon in 1.0 ml acetone
      for 1 h. The desorbed solution was tested by GC-MS and quantified with isotopic
      internal standards. The detection limit, precision and accuracy of the assay were
      evaluated. This method was adopted to detect the epichlorohydrin in drinking
      water for 25 batches in a city. RESULTS: The determination method of
      epichlorohydrin represented a good linear relationship in the range of 0.0645
      3.8700 ug/L, the linear regression equation was Y = 2.828X + 4.91 * 10(-2) (r >
      0.999). When the epichlorohydrin concentration were 0.0806, 0.3230 and 3.2300
      ug/L, the relative standard deviations (RSD) were 7.9%, 4.7% and 3.1%,
      respectively. The average recoveries were from 95.7% to 98.7%. The limit of
      detection (LOD) was 0.015 ug/L, limit of quantification (LOQ) was 0.052 ug/L. The
      content of epichlorohydrin in the 25 cases of drinking water was under the limit
      of detection. CONCLUSION: The method is more simple than the national standard
      method, with high sensitivity, accuracy and good reproducibility, which is
      suitable for detection of the trace amounts of epichlorohydrin in drinking water.

PMID- 23958133
TI  - [Simultaneous determination of 6 pesticides in drinking water by high performance
      liquid chromatography-tandem mass spectrometry with solid phase extraction].
AB  - OBJECTIVE: To develop an analytical method for simultaneous determination of 6
      pesticides, namely bentazone, 2,4-dichlorophenoxyacetic acid,carbofuran,
      carbaryl, atrazine and pentachlorophenol, in drinking water by high performance
      liquid chromatography-tandem mass spectrometry, and thereby to provide a
      reference to revise the Health Standards for Drinking Water (GB/T 5750-2006).
      Meanwhile, to evaluate the content of the above 6 pesticides in the drinking
      water samples supplied by 12 centralized water plants in Jiangsu province.
      METHODS: The 10 ml water sample was acidized by hydrochloric acid to pH <= 2, and
      then concentrated by solid phase extraction cartridge and eluted with acetone.
      The solvent was changed into methanol after drying by nitrogen blow. The target
      compounds were separated by C18 column using methanol/water as mobile phase, and
      detected by mass spectrometry with multi-reaction-monitoring(MRM) mode. The
      repeatability and sensitivity of the assay were evaluated. The drinking water
      samples from the 12 water plants were then detected. RESULTS: In this
      experimental method, the minimum detectable concentration were around 0.02-0.41
      ug/L, with the recovery rate at 75%-115%, and the RSD between 2% and 10%. Under
      the experimental condition, there were no pesticides detected in the drinking
      water samples from the 12 centralized water plants. CONCLUSION: The method is
      efficient and environment-friendly, with little discharge of effluent, which
      could meet the requirement of the drinking water monitor.

PMID- 23958134
TI  - Influenza B virus has global ordered RNA structure in (+) and (-) strands but
      relatively less stable predicted RNA folding free energy than allowed by the
      encoded protein sequence.
AB  - BACKGROUND: Influenza A virus contributes to seasonal epidemics and pandemics and
      contains Global Ordered RNA structure (GORS) in the nucleoprotein (NP), non
      structural (NS), PB2, and M segments. A related virus, influenza B, is also a
      major annual public health threat, but unlike influenza A is very selective to
      human hosts. This study extends the search for GORS to influenza B. FINDINGS: A
      survey of all available influenza B sequences reveals GORS in the (+) and (-)RNAs
      of the NP, NS, PB2, and PB1 gene segments. The results are similar to influenza
      A, except GORS is observed for the M1 segment of influenza A but not for PB1. In
      general, the folding free energies of human-specific influenza B RNA segments are
      less stable than allowable by the encoded amino acid sequence. This is consistent
      with findings in influenza A, where human-specific influenza RNA folds are less
      stable than avian and swine strains. CONCLUSIONS: These results reveal
      fundamental molecular similarities and differences between Influenza A and B and
      suggest a rational basis for choosing segments to target with therapeutics and
      for viral attenuation for live vaccines by altering RNA folding stability.

PMID- 23958135
TI  - Cellulolytic potential of thermophilic species from four fungal orders.
AB  - Elucidation of fungal biomass degradation is important for understanding the
      turnover of biological materials in nature and has important implications for
      industrial biomass conversion. In recent years there has been an increasing
      interest in elucidating the biological role of thermophilic fungi and in
      characterization of their industrially useful enzymes. In the present study we
      investigated the cellulolytic potential of 16 thermophilic fungi from the three
      ascomycete orders Sordariales, Eurotiales and Onygenales and from the zygomycete
      order Mucorales thus covering all fungal orders that include thermophiles.
      Thermophilic fungi are the only described eukaryotes that can grow at
      temperatures above 45 degrees C. All 16 fungi were able to grow on crystalline
      cellulose but their secreted enzymes showed widely different cellulolytic
      activities, pH optima and thermostabilities. Interestingly, in contrast to
      previous reports, we found that some fungi such as Melanocarpus albomyces readily
      grew on crystalline cellulose and produced cellulases. These results indicate
      that there are large differences in the cellulolytic potential of different
      isolates of the same species. Furthermore, all the selected species were able to
      degrade cellulose but the differences in cellulolytic potential and
      thermostability of the secretome did not correlate to the taxonomic position. PCR
      amplification and sequencing of 22 cellulase genes from the fungi showed that the
      level of thermostability of the cellulose-degrading activity could not be
      inferred from the phylogenetic relationship of the cellulases. 

PMID- 23958136
TI  - Barriers and enablers to implementing multiple stroke guideline recommendations:
      a qualitative study.
AB  - BACKGROUND: Translating evidence into practice is an important final step in the
      process of evidence-based practice. Medical record audits can be used to examine
      how well practice compares with published evidence, and identify evidence
      practice gaps. After providing audit feedback to professionals, local barriers to
      practice change can be identified and targetted with focussed behaviour change
      interventions. This study aimed to identify barriers and enablers to implementing
      multiple stroke guideline recommendations at one Australian stroke unit. METHODS:
      A qualitative methodology was used. A sample of 28 allied health, nursing and
      medical professionals participated in a group or individual interview. These
      interviews occurred after staff had received audit feedback and identified areas
      for practice change. Questions focused on barriers and enablers to implementing
      guideline recommendations about management of: upper limb sensory impairments,
      mobility including sitting balance; vision; anxiety and depression; neglect;
      swallowing; communication; education for stroke survivors and carers; advice
      about return to work and driving. Qualitative data were analysed for themes using
      theoretical domains described by Michie and colleagues (2005). RESULTS: Six group
      and two individual interviews were conducted, involving six disciplines. Barriers
      were different across disciplines. The six key barriers identified were: (1)
      Beliefs about capabilities of individual professionals and their discipline, and
      about patient capabilities (2) Beliefs about the consequences, positive and
      negative, of implementing the recommendations (3) Memory of, and attention to,
      best practices (4) Knowledge and skills required to implement best practice; (5)
      Intention and motivation to implement best practice, and (6) Resources. Some
      barriers were also enablers to change. For example, occupational therapists
      required new knowledge and skills (a barrier), to better manage sensation and
      neglect impairments while physiotherapists generally knew how to implement best
      practice mobility rehabilitation (an enabler). CONCLUSIONS: Findings add to
      current knowledge about barriers to change and implementation of multiple
      guideline recommendations. Major challenges included sexuality education and
      depression screening. Limited knowledge and skills was a common barrier.
      Knowledge about specific interventions was needed before implementation could
      commence, and to maintain treatment fidelity. The provision of detailed online
      intervention protocols and manuals may help clinicians to overcome the knowledge
      barrier.

PMID- 23958137
TI  - Determination of microcystins and nodularin (cyanobacterial toxins) in water by
      LC-MS/MS. Monitoring of Lake Marathonas, a water reservoir of Athens, Greece.
AB  - A method for the determination of the hepatotoxic cyanotoxins microcystins (MCs,
      i.e. MC-LR, MC-RR, MC-YR, MC-LA) and nodularin (NOD) in water was developed using
      liquid chromatography with electrospray ionization triple quadrupole mass
      spectrometry (LC-ESI-MS/MS) after solid phase extraction (SPE). New patterns of
      fragmentation of MC-LA were observed under the experimental conditions used. The
      method was fully validated to meet accreditation criteria. Mean recoveries at
      three concentration levels (0.006, 0.1 and 1 MUg L(-1)) ranged between 70 and
      114% with %RSD values generally below 20%. Detection limits were 2 ng L(-1) for
      all hepatotoxins. The method was applied to study the occurrence of MCs and NOD
      in Lake Marathonas, a water reservoir of Athens, over a period from July 2007 to
      December 2010. The protein phosphatase inhibition assay (PPIA) was additionally
      used for fast screening of samples. MC-YR, MC-LR and MC-RR were detected and
      found to vary seasonally with consistent peaks during early autumn, having
      maximum concentrations of 717, 451 and 174 ng L(-1), respectively. The results of
      this study constitute the first report on the presence, concentration levels and
      seasonal variations of MCs in Lake Marathonas. None of the target cyanotoxins
      were detected in treated drinking water samples during the period of the study.

PMID- 23958138
TI  - The impact of climate change on water provision under a low flow regime: a case
      study of the ecosystems services in the Francoli river basin.
AB  - Mediterranean basin is considered one of the most vulnerable regions of the world
      to climate change and with high probability to face acute water scarcity problem
      in the coming years. Francoli River basin (NE Spain), located in this vulnerable
      region is selected as a case study to evaluate the impact of climate change on
      the delivery of water considering the IPCC scenarios A2 and B1 for the time spans
      2011-2040, 2041-2070 and 2071-2100. InVEST model is applied in a low flow river
      as a new case study, which reported successful results after its model
      validation. The studied hydrological ecosystem services will be highly impacted
      by climate change at Francoli River basin. Water yield is expected to be reduced
      between 11.5 and 44% while total drinking water provisioning will decrease
      between 13 and 50% having adverse consequences on the water quality of the river.
      Focusing at regional scale, Prades Mountains and Brugent Tributary provide most
      of the provision of water and also considered highly vulnerable areas to climate
      change. However, the most vulnerable part is the northern area which has the
      lowest provision of water. Francoli River basin is likely to experience
      desertification at this area drying Anguera and Vallverd tributaries.

PMID- 23958139
TI  - A facile approach to fabricate porous nanocomposite gels based on partially
      hydrolyzed polyacrylamide and cellulose nanocrystals for adsorbing methylene blue
      at low concentrations.
AB  - Porous nanocomposite gels were fabricated by a facile method consisting of the
      electrospinning and subsequent heat treatment based on partially hydrolyzed
      polyacrylamide (HPAM) of ultra-high molecular weight, with cellulose nanocrystals
      (CNCs) as crosslinker. The effects of three electrospinning parameters (i.e.,
      solution concentration, composition of solvent mixture, and CNC loading level) on
      morphology and diameter of electrospun fibers were systematically investigated.
      The swelling properties of porous gels and their application in the removal of
      methylene blue dye (as a compound representative of contaminants) were evaluated.
      Electrospun fiber morphologies without beads, branches, and ribbons were achieved
      by optimizing the electrospinning solutions. The thermal crosslinking between
      HPAM and CNCs was realized through esterification, rendering the product
      nanocomposite membranes insoluble in water. Electrospun fibers of approximately
      220 nm in diameter comprised the 3D porous nanocomposite gels, with porosity
      greater than 50%. The porous nanocomposite gels displayed a rapid swelling rate
      and an efficient adsorption capacity in removing methylene blue at low
      concentrations from aqueous solutions.

PMID- 23958140
TI  - Importance of accessible cancer care.
AB  - Accessibility is a fundamental principle of government run health systems.
      Despite this, many factors impair access to care including geography, language,
      socioeconomic status and gender. Waiting for health care is a barrier to access
      that can result in significant anxiety and stress, deterioration in functional
      status and loss of income. Prompt access to diagnosis and treatment are key
      requirements to improving survival and quality of life for patients with cancer.
      This review will focus on studies, programs and policies aimed at improving
      access to care, applicability to patients with lymphoma, and potential impact.
      There is a growing burden on health care systems due to increasing cancer
      incidence and escalating health expenditures. Accordingly, initiatives and
      programs must be evaluated for effectiveness and efficiency. 

PMID- 23958141
TI  - Epidemiology of non-Hodgkin lymphoma.
AB  - Non-Hodgkin Lymphoma (NHL) occurs worldwide although there is notable
      geographical variation in incidence and subtype distribution. These differences
      are due to a combination of demographic, environmental and other unidentified
      factors. A dramatic increase in NHL incidence was seen starting around 1970, with
      subsequent stabilization 10 years ago. Despite this plateau, the number of new
      cases in many countries will increase significantly in coming years due primarily
      to aging populations. In the majority of cases, strong risk factors are not
      identifiable. There is significant epidemiological heterogeneity between NHL
      subtypes, yet cancer registries have tended to consider NHL as a single entity.
      This is one of several epidemiological obstacles discussed.

PMID- 23958142
TI  - Falsification, fabrication, and plagiarism: the unholy trinity of scientific
      writing.

PMID- 23958143
TI  - Pediatric CSI: are protons the only ethical approach?

PMID- 23958144
TI  - Protons for craniospinal radiation: are clinical data important?

PMID- 23958145
TI  - Expanding the number of trainees in radiation oncology: has the pendulum swung
      too far? In regard to Shah.

PMID- 23958146
TI  - ABR examinations: the why, what, and how.
AB  - The American Board of Radiology (ABR) has provided certification for diagnostic
      radiologists and other specialists and subspecialists for more than 75 years. The
      Board certification process is a tangible expression of the social contract
      between the profession and the public by which the profession enjoys the
      privilege of self-regulation and the public is assured that it can expect medical
      professionals to put patients' interests first, guarantees the competence of
      practitioners, and guards the public health. A primary tool used by the ABR in
      fulfilling this responsibility is the secure proctored examination. This article
      sets forth seven standards based on authoritative sources in the field of
      psychometrics (the science of mental measurements), and explains in each case how
      the ABR implements that standard. Readers are encouraged to understand that,
      despite the multiple opinions that may be held, these standards developed over
      decades by experts using the scientific method should be the central feature in
      any discussion or critique of examinations given for the privilege of
      professional practice and for safeguarding the public well-being. 

PMID- 23958148
TI  - Effect of intrafraction prostate motion on proton pencil beam scanning delivery:
      a quantitative assessment.
AB  - PURPOSE: To assess the dosimetric impact caused by the interplay between
      intrafraction prostate motion and the intermittent delivery of proton pencil beam
      scanning (PBS). METHODS AND MATERIALS: A cohort of 10 prostate patients was
      treated with PBS using a bilateral single-field uniform dose (SFUD) modality.
      Bilateral intensity-modulated proton therapy (IMPT) plans were generated for
      comparison. Because beam-on time in PBS was intermittent, the actual beam-on time
      was determined from treatment logs. Prostate motion was generalized according to
      real-time Calypso tracking data from our previously reported prospective photon
      trial. We investigated potential dose deviations by considering the interplay
      effect resulting from the worst-case scenario motion and the PBS delivery
      sequence. RESULTS: For both bilateral-field SFUD and IMPT plans, clinical target
      volume (CTV) D99% coverage was degraded <2% owing to prostate intrafraction
      motion when averaged over the course of treatment, but was >10% for the worst
      fraction. The standard deviation of CTV D99% distribution was approximately 1.2%.
      The CTV coverage of individual fields in SFUD plans degraded as time elapsed
      after the initial alignment, owing to prostate drift. Intensity-modulated proton
      therapy and SFUD demonstrated comparable results when bilateral opposed fields
      were used. Single-field SFUD plans that were repainted twice, which could reduce
      half of the treatment time, resulted in similar CTV coverage as bilateral-field
      plans. CONCLUSIONS: Intrafraction prostate motion affects the actual delivered
      dose to CTV; however, when averaged over the course of treatment, CTV D99%
      coverage degraded only approximately 2% even for the worst-case scenario. The
      IMPT plan results are comparable to those of the SFUD plan, and similar coverage
      can be achieved if treated by SFUD 1 lateral field per day when rescanning the
      field twice to shorten the treatment time and mitigate intrafraction motion.

PMID- 23958147
TI  - Randomized noninferiority trial of reduced high-dose volume versus standard
      volume radiation therapy for muscle-invasive bladder cancer: results of the
      BC2001 trial (CRUK/01/004).
AB  - PURPOSE: To test whether reducing radiation dose to uninvolved bladder while
      maintaining dose to the tumor would reduce side effects without impairing local
      control in the treatment of muscle-invasive bladder cancer. METHODS AND
      MATERIALS: In this phase III multicenter trial, 219 patients were randomized to
      standard whole-bladder radiation therapy (sRT) or reduced high-dose volume
      radiation therapy (RHDVRT) that aimed to deliver full radiation dose to the tumor
      and 80% of maximum dose to the uninvolved bladder. Participants were also
      randomly assigned to receive radiation therapy alone or radiation therapy plus
      chemotherapy in a partial 2 * 2 factorial design. The primary endpoints for the
      radiation therapy volume comparison were late toxicity and time to locoregional
      recurrence (with a noninferiority margin of 10% at 2 years). RESULTS: Overall
      incidence of late toxicity was less than predicted, with a cumulative 2-year
      Radiation Therapy Oncology Group grade 3/4 toxicity rate of 13% (95% confidence
      interval 8%, 20%) and no statistically significant differences between groups.
      The difference in 2-year locoregional recurrence free rate (RHDVRT - sRT) was
      6.4% (95% confidence interval -7.3%, 16.8%) under an intention to treat analysis
      and 2.6% (-12.8%, 14.6%) in the "per-protocol" population. CONCLUSIONS: In this
      study RHDVRT did not result in a statistically significant reduction in late side
      effects compared with sRT, and noninferiority of locoregional control could not
      be concluded formally. However, overall low rates of clinically significant
      toxicity combined with low rates of invasive bladder cancer relapse confirm that
      (chemo)radiation therapy is a valid option for the treatment of muscle-invasive
      bladder cancer.

PMID- 23958149
TI  - Cone-beam computed tomography-guided positioning of laryngeal cancer patients
      with large interfraction time trends in setup and nonrigid anatomy variations.
AB  - PURPOSE: To investigate interfraction setup variations of the primary tumor,
      elective nodes, and vertebrae in laryngeal cancer patients and to validate
      protocols for cone beam computed tomography (CBCT)-guided correction. METHODS AND
      MATERIALS: For 30 patients, CBCT-measured displacements in fractionated
      treatments were used to investigate population setup errors and to simulate
      residual setup errors for the no action level (NAL) offline protocol, the
      extended NAL (eNAL) protocol, and daily CBCT acquisition with online analysis and
      repositioning. RESULTS: Without corrections, 12 of 26 patients treated with
      radical radiation therapy would have experienced a gradual change (time trend) in
      primary tumor setup >=4 mm in the craniocaudal (CC) direction during the
      fractionated treatment (11/12 in caudal direction, maximum 11 mm). Due to these
      trends, correction of primary tumor displacements with NAL resulted in large
      residual CC errors (required margin 6.7 mm). With the weekly correction vector
      adjustments in eNAL, the trends could be largely compensated (CC margin 3.5 mm).
      Correlation between movements of the primary and nodal clinical target volumes
      (CTVs) in the CC direction was poor (r(2)=0.15). Therefore, even with online
      setup corrections of the primary CTV, the required CC margin for the nodal CTV
      was as large as 6.8 mm. Also for the vertebrae, large time trends were observed
      for some patients. Because of poor CC correlation (r(2)=0.19) between
      displacements of the primary CTV and the vertebrae, even with daily online
      repositioning of the vertebrae, the required CC margin around the primary CTV was
      6.9 mm. CONCLUSIONS: Laryngeal cancer patients showed substantial interfraction
      setup variations, including large time trends, and poor CC correlation between
      primary tumor displacements and motion of the nodes and vertebrae (internal tumor
      motion). These trends and nonrigid anatomy variations have to be considered in
      the choice of setup verification protocol and planning target volume margins.
      eNAL could largely compensate time trends with minor prolongation of fraction
      time.

PMID- 23958150
TI  - Increasing the accuracy of volume and ADC delineation for heterogeneous tumor on
      diffusion-weighted MRI: correlation with PET/CT.
AB  - PURPOSE: To improve the accuracy of volume and apparent diffusion coefficient
      (ADC) measurements in diffusion-weighted magnetic resonance imaging (MRI), we
      proposed a method based on thresholding both the b0 images and the ADC maps.
      METHODS AND MATERIALS: In 21 heterogeneous lesions from patients with metastatic
      gastrointestinal stromal tumors (GIST), gross lesion were manually contoured, and
      corresponding volumes and ADCs were denoted as gross tumor volume (GTV) and gross
      ADC (ADC(g)), respectively. Using a k-means clustering algorithm, the probable
      high-cellularity tumor tissues were selected based on b0 images and ADC maps. ADC
      and volume of the tissues selected using the proposed method were denoted as
      thresholded ADC (ADC(thr)) and high-cellularity tumor volume (HCTV),
      respectively. The metabolic tumor volume (MTV) in positron emission tomography
      (PET)/computed tomography (CT) was measured using 40% maximum standard uptake
      value (SUV(max)) as the lower threshold, and corresponding mean SUV (SUV(mean))
      was also measured. RESULTS: HCTV had excellent concordance with MTV according to
      Pearson's correlation (r=0.984, P<.001) and linear regression (slope = 1.085,
      intercept = -4.731). In contrast, GTV overestimated the volume and differed
      significantly from MTV (P=.005). ADC(thr) correlated significantly and strongly
      with SUV(mean) (r=-0.807, P<.001) and SUV(max) (r=-0.843, P<.001); both were
      stronger than those of ADC(g). CONCLUSIONS: The proposed lesion-adaptive
      semiautomatic method can help segment high-cellularity tissues that match
      hypermetabolic tissues in PET/CT and enables more accurate volume and ADC
      delineation on diffusion-weighted MR images of GIST.

PMID- 23958151
TI  - Benefits and drawbacks of short-course preoperative radiotherapy in rectal cancer
      patients aged 75 years and older.
AB  - PURPOSE: To study incidence of local recurrences, postoperative complications and
      survival, in patients with rectal carcinoma aged 75 years and older, treated with
      either surgery and pre-operative 5 * 5 Gy radiotherapy or surgery alone. PATIENTS
      AND METHODS: A random sample of patients aged over 75 years with pT2-T3, N0-2, M0
      rectal carcinoma diagnosed between 2002 and 2004 in the Netherlands was included,
      treated with surgery alone (N = 296) or surgery in combination with pre-operative
      radiotherapy (N = 346). Information on local recurrent disease, postoperative
      complications, ECOG-performance score and comorbidity was gathered from the
      medical files. RESULTS: Local recurrences developed less frequently in patients
      treated with pre-operative radiotherapy compared to surgery alone (2% vs 6%, p =
      0.002). Postoperative complications developed more frequently in irradiated
      patients (58% vs 42%, p < 0.0001). Especially deep infections (anastomotic
      leakage, pelvic abscess) were significantly increased in this group (16% vs 10%,
      p = 0.02). 30-day mortality was equal in both groups (8%). A significant increase
      in postoperative complication rate and 30-day mortality was only seen in those
      with "severe comorbidity" compared to patients without comorbidity (respectively
      58% and 10% vs 43% and 3%), COPD (59% and 12%), diabetes (60% and 11%) and
      cerebrovascular disease (62% and 14%). In multivariable analysis, postoperative
      complications predicted 5-year survival. CONCLUSION: Elderly patients receiving
      pre-operative radiotherapy show a lower local recurrence rate. However, as
      incidence rates of local recurrent disease are low and incidence of postoperative
      complications is increased in irradiated patients, omitting preoperative RT may
      be suitable in elderly patients with additional risks for complications or early
      death.

PMID- 23958152
TI  - Factors affecting job satisfaction and retention of medical laboratory
      professionals in seven countries of Sub-Saharan Africa.
AB  - Effective implementation and sustainability of quality laboratory programmes in
      Sub-Saharan Africa relies on the development of appropriate staff retention
      strategies. Assessing the factors responsible for job satisfaction and retention
      is key for tailoring specific interventions aiming at improving the overall
      impact of health programmes. A survey was developed to assess these factors among
      224 laboratorians working in the laboratory programme the University of Maryland
      implemented in seven Sub-Saharan African countries. Lack of professional
      development was the major reason for leaving the previous job for 28% of
      interviewees who changed jobs in the past five years. Professional
      development/training opportunities was indicated by almost 90% (195/224) of total
      interviewees as the most important or a very important factor for satisfaction at
      their current job. Similarly, regular professional development/opportunities for
      training was the highest rated incentive to remain at their current job by 80%
      (179/224). Laboratory professionals employed in the private sector were more
      likely to change jobs than those working in the public sector (P = 0.002). The
      findings were used for developing specific strategies for human resources
      management, in particular targeting professional development, aiming at improving
      laboratory professionals within the University of Maryland laboratory programme
      and hence its long-term sustainability.

PMID- 23958153
TI  - Bad design, bad practices, bad bugs: frustrations in controlling an outbreak of
      Elizabethkingia meningoseptica in intensive care units.
AB  - BACKGROUND: Elizabethkingia meningoseptica is a nosocomial-adapted Gram-negative
      bacillus intrinsically resistant to antibiotics commonly used in the intensive
      care setting. An outbreak investigation commenced when five patients developed E.
      meningoseptica infection in two intensive care units (ICUs). METHODS: Analysis of
      laboratory data, case reviews, ICU workflows and extensive environmental sampling
      were undertaken. Molecular typing was performed using repetitive element
      palindromic polymerase chain reaction. Follow-up studies after interventions
      included environmental monitoring and a survey of staff compliance with
      interventions. FINDINGS: Laboratory data revealed increasing incidence of E.
      meningoseptica colonization or infection in ICU patients compared with preceding
      years. E. meningoseptica was cultured from 44% (35/79) of taps, but not from
      other sources. Hand hygiene sinks were used for disposal of patient secretions
      and rinsing re-usable patient care items. Sinks misused in this way were
      contaminated more often than sinks that were not misused (odds ratio 4.38, 95%
      confidence interval 1.68-11.39; P = 0.004). Molecular typing revealed that
      patient isolates had identical patterns to several isolates from hand hygiene
      taps. An urgent education programme was instituted to change these practices.
      Taps were cleaned systematically and aerators were changed. A temporary reduction
      in case numbers was achieved. Recolonization of taps was demonstrated on follow
      up environmental screening, and cases recurred after two months. A survey
      revealed that 77.3% (163/213) of nursing staff still misused sinks due to time
      constraints or other problems adhering to the interventions. CONCLUSION:
      Introduction of non-sanctioned practices due to suboptimal unit design may have
      unintentional consequences for ICU patients. Room design and staff workflows must
      be optimized for patient safety as lapses in procedure can inadvertently put
      patients at risk.

PMID- 23958155
TI  - Production of 2,3-butanediol from cellulose and Jatropha hulls after ionic liquid
      pretreatment and dilute-acid hydrolysis.
AB  - Abundant Jatropha waste is a promising renewable feedstock for the production of
      sugars and 2,3-butanediol fermentation. To obtain high yield of water-soluble
      products and high concentration of reducing-sugars, ionic liquid (IL)
      pretreatment and dilute acid hydrolysis at 150 degrees C were combined in this
      work. The destruction of crystalline structure and increase surface area of
      biomasses after IL-pretreatment, made their hydrolysis more efficient. Compared
      with original cellulose, after IL-pretreatment, both the yield and concentration
      of reducing-sugars increased by 139%, and the water-soluble products yield
      increased by 128% after hydrolysis. Compared with water-washed Jatropha hulls,
      after IL-pretreatment, the yield and concentration of reducing-sugars increased
      by 80% and 76%, respectively, and the water-soluble products yield increased by
      70% after hydrolysis. IL-pretreatment benefited the fermentation of Jatropha hull
      hydrolysate with 66.58% diol yield and its productivity increased from 0.35 to
      0.40 g/(L . h). 

PMID- 23958154
TI  - A self-management program for employees with complaints of the arm, neck, or
      shoulder (CANS): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Complaints of the arm, neck, or shoulder (CANS) have a multifactorial
      origin and cause considerable work problems, including decreased work
      productivity, sickness absence, and, ultimately, job loss. There is a need for
      intervention programs for people with CANS. Self-management is an approach used
      in chronic disease care to improve self-efficacy and wellness behaviors to
      facilitate participants to make informed choices and carry them out. This study
      will evaluate the effectiveness of a self-management program (including ehealth)
      and compare it to usual care among employees with chronic CANS (lasting >3
      months). METHODS/DESIGN: This is a randomized controlled trial in which 142
      participants will be recruited and randomized (with pre-stratification) to either
      the intervention group (IG) or control group (CG). The IG will participate in a
      self-management program consisting of six group sessions and an ehealth module.
      The CG is allowed to use all usual care available. The primary outcome of the
      study is the self-reported disability of arm, shoulder, and hand, measured with
      the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH). Secondary
      outcomes include: absenteeism, pain in the previous week, quality of life,
      catastrophizing pain, self-efficacy, workstyle, presenteeism, fatigue, the use of
      usual care, and limitations experienced on the job. Data are collected at
      baseline and at 3, 6, and 12 months follow-up. DISCUSSION: Following the process
      of intervention mapping we developed a self-management program to suit and
      alleviate the problems and needs of employees with CANS. A strength of the study
      is that our intervention is specifically tailored to match the needs of employees
      with CANS. The study also has some potential weaknesses (for example, use of co
      interventions, combination of group sessions and ehealth, self-reporting of data
      and possible contamination, Hawthorne effect, and recall or information bias)
      which are discussed. TRIAL REGISTRATION: The trial is registered with the Dutch
      Trial Register (http://www.trialregister.nlNTR3816): (January 2013). The first
      participant was randomized in September 2012.

PMID- 23958156
TI  - Promoting universal financial protection: contracting faith-based health
      facilities to expand access--lessons learned from Malawi.
AB  - BACKGROUND: Public-private collaborations are increasingly being utilized to
      universalize health care. In Malawi, the Ministry of Health contracts selected
      health facilities owned by the main faith-based provider, the Christian Health
      Association of Malawi (CHAM), to deliver care at no fee to the most vulnerable
      and underserved populations in the country through Service Level Agreements
      (SLAs). This study examined the features of SLAs and their effectiveness in
      expanding universal coverage. The study involved a policy analysis focusing on
      key stakeholders around SLAs as well as a case study approach to analyse how
      design and implementation of SLAs affect efficiency, equity and sustainability of
      services delivered by SLAs. METHODS: The study employed both qualitative and
      quantitative research methods to address the research questions and was conducted
      in five CHAM health facilities: Mulanje Mission, Holy Family, and Mtengowanthenga
      Hospitals, and Mabiri and Nkope Health Centres. National and district level
      decision makers were interviewed while providers and clients associated with the
      health facilities were surveyed on their experiences. A total of 155 clients from
      an expected 175 were recruited in the study. RESULTS: The study findings revealed
      key aspects of how SLAs were operating, the extent to which their objectives were
      being attained and why. In general, the findings demonstrated that SLAs had the
      potential to improve health and universal health care coverage, particularly for
      the vulnerable and underserved populations. However, the findings show that the
      performance of SLAs in Malawi were affected by various factors including lack of
      clear guidelines, non-revised prices, late payment of bills, lack of
      transparency, poor communication, inadequate human and material resources, and
      lack of systems to monitor performance of SLAs, amongst others. CONCLUSIONS:
      There was strong consensus and shared interest between the government and CHAM
      regarding SLAs. It was clear that free services provided by SLAs had a great
      impact on the impoverished locals that used the facilities. However, lack of
      supporting systems, inadequate infrastructure and shortage of health care
      providers affected SLA performance. The paper provides recommendations to policy
      makers for the replication and strengthening of SLA implementation in the roll
      out of universalization policy.

PMID- 23958157
TI  - [The current status and perspective of laparoscopic gastrectomy for gastric
      cancer].

PMID- 23958158
TI  - [Current status and prospect of laparo-endoscopic single site surgery in general
      surgery].

PMID- 23958159
TI  - [A comparative study of laparoscopic-assisted and open distal gastrectomy for
      advanced gastric cancer].
AB  - OBJECTIVE: To evaluate the safety, feasibility and the long-term outcomes of
      laparoscopy-assisted gastrectomy (LAG) for advanced gastric cancer (AGC).
      METHODS: The clinical and follow-up data of 46 cases after LAG from June 2008 to
      December 2009 were analyzed, and compared with 85 cases after conventional open
      gastrectomy (OG) for advanced gastric cancer at the same period at our hospital.
      The surgical safety, postoperative recovery, complications, radical degree,
      survival rate were compared. RESULT: As compared with OG group, operation time
      was longer in LATG group ((274 +/- 78) min vs. ( 217 +/- 41) min, t = 4.635, P =
      0.000). Estimated blood loss in the LAG group ((254 +/- 112) ml) was
      significantly less than in the OG group (t = 3.942, P = 0.000). Time to
      ambulation ((63 +/- 16) hours), first flatus ((77 +/- 20) hours), resumed liquid
      diet ((88 +/- 15) hours), duration of analgesic medication ((53 +/- 20) hours)
      and postoperative hospital stay ((11.1 +/- 4.6) days) were significantly shorter
      in the LAG group (t = 5.549, 6.508, 9.436, 9.464 and 2.980 respectively, all P <
      0.01). The distance of the proximal and distal resection margin were (5.7 +/-
      1.4) cm and (3.9 +/- 1.5) cm in LAG group, (5.8 +/- 1.1) cm and (4.7 +/- 1.5) cm
      in OG group respectively, but the difference was not significant. The number of
      lymph node dissections was also similar, (30.5 +/- 10.4) in LAG group and (32.6
      +/- 12.3) in OG group (t = 0.960, P = 0.339). The incidence of postoperative
      complications and mortality rate in LAG group (8.7% and 0 respectively) were also
      lower than in the OG group, with no statistically significant difference (P >
      0.05). The mean follow-up was 31.0 months (range 6-48 months), and the cumulative
      survival of the 2 groups was similar (chi(2) = 1.594, P = 0.207). CONCLUSIONS:
      Laparoscopy-assisted gastrectomy for advanced gastric cancer is not significantly
      different with open surgery in surgical safety, radical degree, and survival
      rate. It is less traumatic and of fewer complications.

PMID- 23958160
TI  - [The effect of drainage in cavities on preventing from grade B and C of the
      pancreatic fistula after pancreaticoduodenectomy].
AB  - OBJECTIVE: To explore the effect of drainage in cavities on preventing from grade
      B and C of the pancreatic fistula after pancreaticoduodenectomy (PD). METHODS:
      From June 2008 to June 2010, the medical team had performed the operations of
      digestive tract reconstruction by the same way in 68 cases with PD. There were 43
      male and 25 female patients, with a mean age of (64 +/- 3) years. The patients
      were simply randomly divided into drainage in cavities group (DC, n = 32) and
      conventional drainage group (CD, n = 36) according to the different drainage way.
      The methods of drainage in cavities were composed of three aspects which include
      drainage in main pancreatic duct, drainage around cholecystojejunostomy
      anastomosis and peripancreatic drainage. The clinical parameters of the two
      groups were collected. The characteristics of the drainage juice which include
      color, volume and amylase value in the two groups were compared. The incidence
      and severity grading of pancreatic fistula between the two groups were evaluated.
      RESULTS: The average of amylase value and the peripancreatic drainage flow were
      (1401 +/- 8) U/L and (49 +/- 5) ml in the DC group. Their average in the CD group
      were (2160 +/- 13) U/L and (76 +/- 4) ml. There was significant statistical
      difference in the peripancreatic drainage flow between the two groups (t = 2.597,
      P = 0.031). The amylase values of the drainage juice between the two groups were
      of no statistical difference (P > 0.05). According to the definition of
      pancreatic fistula by an international study group, the incidence of pancreatic
      fistula in the DC group was 25.0% (8/32) and the CD group 30.5% (11/36) (P >
      0.05). The proportion of grades B and C of pancreatic fistula in the DC group had
      statistical difference compared with one of the CD group (chi(2) = 4.797, P =
      0.029). CONCLUSION: Drainage in cavities could significantly decrease and the
      occurring ratio of grade B and C of pancreatic fistula after PD.

PMID- 23958161
TI  - [The application of popliteal vein anatomy study and valve construction
      procedure].
AB  - OBJECTIVE: To analyze anatomy data of popliteal veins (PV), with the purpose of
      selection of popliteal venous valves construction segment via venography, and to
      evaluate the surgical results. METHODS: From February 1998 to November 2010,
      after analyzing the popliteal vessel anatomy data of 39 limbs and related
      phlebography research of 862 cases, 102 patients (69 male and 33 female patients,
      aged from 48 to 71 years, mean 59 years) with severe deep venous insufficiency
      were selected for popliteal venous valve construction procedures. Doppler
      ultrasound, continuous dynamic venography, and intraoperative venous pressure
      measurements were used to assess the hemodynamic changes pre- and
      postoperatively. Venous clinical severity score (VCSS) were used to evaluate long
      term results of deep venous valve construction procedures. RESULT: In the 102
      patients, 93.7% patients had one pair of valves in popliteal vein (PV), locating
      in the distal 1/3 segment of PV, with gastrocnemius veins (GV) joining with PV
      above PV valves. Postoperative blood flow volume of the PV was significantly
      higher than the preoperative volume (732.3 ml/min vs. 150.2 ml/min, t = 8.979, P
      < 0.001). The proximal pressure was significantly lower than the distal pressure
      ((12 +/- 3) cm H(2)O vs. (15 +/- 3) cm H(2)O, 1 cm H(2)O = 0.098 kPa, t = 8.049,
      P < 0.001). VCSS score was significantly lower after the surgery ((34 +/- 15) cm
      H(2)O vs. (41 +/- 14) cm H(2)O, t = 59.780, P < 0.001). Pre- and postoperative
      hemodynamic changes and VCSS scores were statistically significant (9.3 +/- 1.9
      vs. 1.8 +/- 1.0, t = 59.780, P < 0.001). Mean follow-up were 8.9 years with an
      ulcer recovery rate of 96.3%, and a 3.7% ulcer recurrent rate. CONCLUSIONS:
      Popliteal vessel anatomy study and venography research provide critical
      information for the PV valve construction part selection, which stayed proximal
      to the communications of GV and PV. Restoration of gastrocnemius pump function
      and satisfactory long-term efficacy are received after valve construction.

PMID- 23958162
TI  - [Surgical classification and therapeutic strategy for metastases of proximal
      femur].
AB  - OBJECTIVE: To establish a surgical classification system for metastases of
      proximal femur and discuss the therapeutic strategy with retrospective analysis
      and literature review. METHODS: The data of 99 patients who underwent a total of
      102 operations for femoral metastatic lesions from January 2003 to December 2011
      was analyzed. There were 50 males and 49 females, and the median age was 56 years
      (range 15-87 years). The most common diagnosis was lung cancer (30 cases),
      followed by breast cancer (17 cases). All femoral lesions were divided into 4
      types (I-IV) with different anatomic site and biomechanic characteristic. The
      patients with various surgical reconstruction mode and postoperative follow-up
      data were recorded. RESULT: There were 65 side who received widely or marginal
      resection and 37 side who received intralesional resection. The patients were
      operated with bipolar hip prosthesis (n = 3), ordinary total hip replacement
      (THR) (n = 10), bipolar tumor prosthesis (n = 48), THR with tumor prosthesis (n =
      8), intramedullary nailing (n = 21), and plate/screw (n = 12). The estimated
      survival for the 99 patients was 10.3 months. Type I, II, III and IV patients
      with postoperative American Society of bone and soft tissue tumors-93 rating were
      86.5%, 77.3%, 81.3% and 69.1%. Patients with type IV were worse compared with the
      other 3 groups (t = 4.763, P = 0.031). The 10 operations were followed by
      complications of any kind. Complication rate of patients with type IV were 3/12,
      and it was significantly higher than the other 3 groups of patients (chi(2) =
      4.018, P = 0.045). CONCLUSIONS: The classifications and corresponsive surgical
      methods for upper femur metastases had some superiority in hinting prognosis and
      guiding treatment.

PMID- 23958163
TI  - [The microbiology and antimicrobial susceptibility of the infected knee
      arthroplasty].
AB  - OBJECTIVES: To describe the microbiology, antimicrobial susceptibility of
      patients proven prosthetic joint infection (PJI) after primary total knee
      arthroplasty (TKA)and to provide reference for the diagnosis and treatment of
      this complication. METHODS: The medical data of the patients with infected knee
      arthroplasty, who were managed with revision surgery between January 1995 to
      December 2011 were reviewed. Twenty-nine cases were identified and majority of
      the patients were female (23/29). Diagnosis of PJI after primary TKA was between
      1 week and 10 years (average 24.3 months). The microbiology and antimicrobial
      susceptibility were analyzed. RESULT: The overall positive rate of cultures was
      65.5% (19/29). The most common organisms identified were Coagulase-negative
      Staphylococcus (CNS) (7/19) and Staphylococcus Aureus (SA) (5/19). Rare pathogens
      of Mycobacterium (2/19) and fungi (1/19) were also identified. Vancomycin was the
      most effective antibiotics with overall sensitivity rates of 100%.Resistant and
      rare pathogens were all in type IV infection. CONCLUSIONS: Gram-positive
      bacterias are the main pathogen, resistant and rare pathogens should be payed
      attention to. Antibiotic treatment for infected TKA should be based on the
      results of drug susceptibility. Vancomycin allows infected knee arthroplasties
      before the result.

PMID- 23958164
TI  - [Knee arthroscopic resection of articular capsule valvular treat popliteal
      cysts].
AB  - OBJECTIVE: To retrospective study the results of arthroscopic resection of
      articular capsule valvular treated popliteal cysts and examined the incidence of
      complication. METHODS: From July 2007 to July 2010, 45 patients with symptomatic
      popliteal cysts such as knee pain and limitation of motion were treated with
      arthroscopic technique to resect the connecting valvular mechanism at
      posteromedial compartment of articular capsule. Through the posteromedial viewing
      portal and cyst resection working portal, resected the valvular mechanism by
      shaver and plasma cutter, associated intra-articular pathology was treated
      simultaneously. The functional outcome was evaluated by employed Rauschning and
      Lindgren score before the surgery and the last follow-up. By using of Wilcoxon
      rank sum test to statistics analyze the clinic outcome. RESULT: In all cases, 40
      patients were found the associated intra-articular pathology, the incidence was
      88.9%.The intra-articular pathology was medial meniscus tear (27 cases, 60.0%),
      lateral meniscus tear (20 cases, 44.4%), cartilage lesion (28 cases, 62.2%),
      which composed with patellofemoral joint (12 cases, 26.7%),medial condyles of
      femur (10 cases, 22.2%),lateral condyles of femur (6 cases, 13.3%). The anterior
      cruciate ligment injury was found in 2 cases, the incidence was 4.4%. All the
      patients achieved symptoms relief postoperative, such as posterior knee
      discomfort and swelling after activities.The Rauschning and Lindgren score was
      improved 1-2 grade in average (Z = -6.092, P = 0.00). The recurrence rate was
      2.2%. All the incision healed good. No major complications were encountered such
      as saphenous nerve, great saphenous vein, blood vessel in popliteal injury.
      CONCLUSIONS: Arthroscopic resection of articular capsule valvular treatment of
      popliteal cyst and treatment of associated intra-articular pathology are
      effective and safe. This surgery technique has more minimally trauma and lower
      recurrence rate.The clinic results in short term are excellent.

PMID- 23958165
TI  - [The correlation between Chlamydiae pneumonia and carotid atherosclerosis].
AB  - OBJECTIVES: To study the correlation between Chlamydiae pneumonia and carotid
      atherosclerosis, and the correlation between the infection of Chlamydiae
      pneumonia and ischemic events. METHODS: The study group consisted of 19 patients
      who underwent unilateral carotid endarterectomy surgery during the period from
      January 2010 to December 2011, and the atherosclerotic plaque specimens were
      harvested from these patients. The control group consisted of 10 patients who
      underwent extracranial-intracranial bypass surgery during the same period, and
      the normal external carotid artery specimens were got from these patients. The
      clinical data between the two groups had comparability. The presence of
      Chlamydiae pneumonia in atherosclerotic plaque and normal artery tissue were
      investigated by immunohistochemistry. The expression of Toll-like receptor 2
      (TLR2), tumor necrosis factor-alpha (TNF-alpha) and vascular cell adhesion
      molecule-1 (VCAM-1) in the atherosclerotic plaque infected with Chlamydiae
      pneumonia were also detected. Data were analyzed using Fisher's exact test.
      RESULT: Chlamydiae pneumonia was found in 9 of 19 atherosclerotic plaques, while
      no positive result was found in control group. The statistical analysis showed a
      significant difference (P = 0.011). Among the 19 patients in study group, 15 of
      them had ischemic events, and Chlamydiae pneumonia was found in 9 of these 15
      patients; while the other 4 patients didn't have any ischemic events and no
      Chlamydiae pneumonia was found in them, but there was no statistical different
      between them (P = 0.087). Through immunohistochemistry, the expression of
      Chlamydiae pneumonia, TLR2, TNF-alpha and VCAM-1 were found in same area.
      CONCLUSIONS: There is a correlation between Chlamydiae pneumonia and carotid
      atherosclerosis.And there might be a correlation between Chlamydiae pneumonia and
      cerebral ischemic events.

PMID- 23958166
TI  - [Effects of intrathecal injection of methylprednisolone sodium succinate in acute
      spinal cord injury rabbits].
AB  - OBJECTIVE: To investigate the effects and apoptosis of intrathecal injection of
      Methylprednisolone Sodium Succinate (MPss) for acute spinal cord injury (SCI) in
      New Zealand rabbits. METHODS: Seventy-two healthy New Zealand rabbits were used
      for the procedure and were randomly divided into two groups: SCI group and SHAM
      group, which was both divided into 6 subgroups, such as the vehicle group, the
      MPss intrathecal injection groups (1.5 mg/kg, 3.0 mg/kg, 6.0 mg/kg group), the
      MPss intravenous injection group and the combined injection group. TARLOV score
      was tested daily to evaluate the motor function. The rabbits were sacrificed 7
      days after the surgery and the thoracic spinal cord sections and the sacral
      sections where MPss was injected were harvested for HE and TUNEL staining. Two
      Factors Repeated Measures analysis of variance for TARLOV scores tested at
      various times and One-Way ANOVA analysis of variance for data between groups were
      used. RESULT: Seven days after surgery in SCI group, there was no statistical
      difference between the TARLOV scores of intrathecal injection of MPss 3.0 mg/kg
      group, 6.0 mg/kg group and MPss intravenous injection group (P > 0.05), which
      were all better than the vehicle group (F = 4.762, P < 0.05). Referring to the
      lymphocyte infiltration at the injury site in SCI group, there was statistical
      difference between MPss intrathecal injection 6.0 mg/kg group (1.33 +/- 0.21) and
      the vehicle group (2.67 +/- 0.21) (F = 5.793, P < 0.05) and no statistical
      difference between intrathecal injection of MPss 6.0 mg/kg group and MPss
      intravenous injection group (P > 0.05). As for the lymphocyte infiltration at the
      intrathecal injection site in SHAM group, there was statistical difference
      between MPss intrathecal injection 6.0 mg/kg group (2.50 +/- 0.55) and the
      vehicle group (0.50 +/- 0.55) (F = 17.333, P < 0.05). TUNEL staining in SCI group
      showed statistical difference between MPss intrathecal injection 6.0 mg/kg group
      (6.3 +/- 1.5) and the vehicle group (20.3 +/- 2.2) (F = 71.279, P < 0.05).
      CONCLUSIONS: Intrathecal injection of MPss can improve the functional recovery of
      lower limb and decrease apoptosis of neuron cells,which can provide same effects
      as the traditional intravenous injection of MPss in New Zealand rabbits.

PMID- 23958167
TI  - [The changes of extracellular matrix in adult degenerative nucleus pulposus cells
      with stiring microcarrier culture system in vitro].
AB  - OBJECTIVE: To evaluate the biological effect on the synthesis of the
      extracellular matrix (ECM) in the cultivation of adult degenerative nucleus
      pulposus cells using the stiring microcarrier system in vitro. METHODS: Thirty
      four specimens were collected after intervertebral fusion operations of the
      patients with intervertebral disc herniation diseases from September 2005 to May
      2009. The specimens were then randomly allocated into 2 groups for in vitro
      cultivation: monolayer culture group and microcarrier culture group. On the
      exponential phase, SP-ABC immunohistochemical staining and Western blot
      quantitative analysis were conducted in the two groups to detect the collagen
      type I and II. Proteoglycan contents of two groups in different growth phases
      were detected with (35)S-sulfate incorporation assay. RESULT: The expressions of
      collagen type I and II in microcarrier culture group were significantly higher
      than those in monolayer culture group: SP-ABC immunohistochemical staining
      (collagen type I: 32.5 +/- 4.4 vs. 15.2 +/- 1.2, t = 2.871, P < 0.01; collagen
      type II: 43.6 +/- 4.1 vs. 23.1 +/- 2.2, t = 2.375, P < 0.05); Western blot
      quantitative analysis (collagen type I: 0.62 +/- 0.08 vs. 0.50 +/- 0.06, t =
      3.327, P < 0.01; collagen type II: 1.46 +/- 0.08 vs. 0.86 +/- 0.04, t = 2.453, P
      < 0.05). Nucleus pulposus cells cultivated in stiring microcarrier system showed
      significantly increased proteoglycan synthesis than monolayer culture group does
      on both exponential phase and stationary phase (exponential phase: 34 821 +/- 312
      vs. 21 046 +/- 673, t = 2.134, P < 0.05; stationary phase: 45 134 +/- 175 vs. 32
      193 +/- 713, t = 2.801, P < 0.01). CONCLUSIONS: The expression of collagen type
      I, II and proteoglycan of adult degenerative nucleus pulposus cells are positive
      regulated by the stiring microcarrier system, which can be used in the mass
      amplification of the adult degenerative nucleus pulposus cells.

PMID- 23958168
TI  - [Suppression of experimental abdominal aortic aneurysm by saturated hydrogen
      saline: a preliminary study with rats].
AB  - OBJECTIVE: To investigate the effects of saturated hydrogen saline on the
      prevention of abdominal aortic aneurysm (AAA) induced by calcium chloride in a
      rat model. METHODS: In healthy male Sprague-Dawley rats, AAA was induced by
      infiltration of abdominal arota with 0.5 mol/L calcium chloride. Saturated
      hydrogen saline (5 ml.kg(-1).d(-1)) or saline was administred intraperitoneally
      once daily. Twenty-eight days later, the diameter of the aorta was measured, and
      the aortic tissue was exercised for histological examination. Pro-inflammatory
      cytokines (tumor necrosis factor alpha (TNF-alpha), IL-1beta) in AAA tissue were
      detected with ELISA. The protein expression and mRNA expression of matrix
      metalloproteinase 2 (MMP-2) and MMP-9 in AAA tissue were observed by
      immunohistochemistry staining and real-time PCR. RESULT: The aorta diameter of
      the experiment group and control group were (2.2 +/- 0.3) mm and (3.4 +/- 0.5)
      mm, the tissue IL-1beta levels were (81 +/- 29) ng/L and (165 +/- 51) ng/L, the
      tissue TNF-alpha levels were (109 +/- 46) ng/L and (360 +/- 51) ng/L, the
      relative mRNA expressions were 2.4 +/- 1.0 and 11.8 +/- 2.9, the relative mRNA
      expressions were 2.9 +/- 0.6 and 6.7 +/- 1.0 (t = 4.055 to 10.406, P < 0.05).
      Compared with the control group, the infiltration of inflammation, the injury of
      elastic fibers in the vessel wall, and the positive expression of MMP-2 and 9
      protein of the experiment group were all reduced. CONCLUSIONS: Saturated hydrogen
      saline prevents the degradation of elastin in vessel wall and ameliorates the
      formation and development of AAA, which may be associated with its anti
      inflammatory effects, thereby reduces the MMP-2 and 9 mRNA and protein
      expression.

PMID- 23958169
TI  - [Transforming growth factor beta1 cooperates with stromal cell derived factor 1
      to affect the proliferation of hepatic oval cells via beta-catenin inactivation].
AB  - OBJECTIVE: To investigate the role of stromal cell derived factor 1 (SDF-1) on
      the proliferation of hepatic oval cells, and the influencing factors. METHODS:
      Flow cytometry was used to detect the expression of CXCR4 on the cell surface
      when WB-F344 cells were growing in the culture medium with and without
      transforming growth factor beta1 (TGF-beta1) respectively. Western bolt was used
      to detect the expression of beta-catenin and its phosphorylation level. The
      translocation of beta-catenin was shown by confocal microscopy analysis. Q-RT-PCR
      was used in detecting the beta-catenin downstream gene expression such as Ccnd1
      and c-Myc. MTT was used to detect the proliferation of WB-F344 cells which were
      treated by SDF-1 + TGF-beta1 and those cells exposed to SDF-1 or TGF-beta1 only,
      as well as of the negative control group. RESULT: WB-F344 cells rarely express
      CXCR4 under conventional circumstance, but this receptor can be up-regulated when
      the culture medium contain a modest amount of TGF-beta1 (the rate of CXCR4
      positive cell increased by 39.5%). The bond of SDF-1 to CXCR4 results in the
      phosphorylation of beta-catenin, and its inactivation. SDF-1 alone didn't affect
      the proliferation of WB-F344 cells (0.512 +/- 0.010 vs. 0.513 +/- 0.008, t =
      0.337, P > 0.05), while TGF-beta1 group show a slight decrease of cell population
      (0.393 +/- 0.007,t = 28.001, P < 0.05). But when TGF-beta1 combined with SDF-1,
      the proliferation of WB-F344 was more weakened than TGF-beta1 group, and the
      difference was statistically significant (0.272 +/- 0.009,t = 32.204, P < 0.05).
      CONCLUSIONS: TGF-beta1 can up-regulate the expression of CXCR4 in hepatic oval
      cells, and then inhibit the proliferation of hepatic oval cells via inactivating
      beta-catenin in vitro.

PMID- 23958170
TI  - [Meta-analysis of adjuvant chemotherapy on prognosis for gastric cancer patients
      after D2 dissection].
AB  - OBJECTIVE: To evaluate efficacy of adjuvant chemotherapy after D2 dissection on
      survival for patients with gastric cancer. METHODS: Randomized clinical trials
      (RCT) that compared adjuvant chemotherapy after D2 dissection with D2 dissection
      alone for gastric cancer were searched with Pubmed, Cochrane, Embase and CBM
      databases. Eligible trials published between 1990 and 2012 were included in the
      study. The quality of RCTs was assessed by the Jadad scale. Data synthesis and
      statistical analysis were performed by RevMan 5.1 software. RESULT: Eight RCTs
      with 3633 patients were included in this study. Among them, 1824 patients
      received adjuvant chemotherapy and 1809 patients didn't. Adjuvant chemotherapy
      was associated with a significant benefit in terms of overall survival (RR =
      0.76, 95% CI: 0.69-0.84), disease free survival (RR = 0.72, 95%CI: 0.66-0.80) and
      recurrence rate (RR = 0.69, 95% CI: 0.62-0.77). CONCLUSION: Adjuvant chemotherapy
      was associated with survival benefit for gastric cancer after D2 dissection.

PMID- 23958171
TI  - Hypercortisolaemia due to ectopic adrenocorticotropic hormone secretion by a
      nasal paraganglioma: a case report and review of the literature.
AB  - BACKGROUND: Adrenocorticotropic hormone-producing extraadrenal paragangliomas are
      extremely rare. We present a case of severe hypercortisolemia due to ectopic
      adrenocorticotropic hormone secretion by a nasal paraganglioma. CASE
      PRESENTATION: A 70-year-old Caucasian woman, was emergently admitted to our
      department with supraventricular tachycardia, oedema of face and extremities and
      hypertensive crisis. Initial laboratory evaluation revealed severe hypokalemia
      and hyperglycemia without ketoacidosis, although no diabetes mellitus was
      previously known. Computed tomography revealed a large tumor obliterating the
      left paranasal sinus and a left-sided adrenal mass. After cardiovascular
      stabilisation, a thorough hormonal assessment was performed revealing marked
      adrenocorticotropic hormone-dependent hypercortisolism. Due to the presence of a
      cardiac pacemaker magnetic resonance imaging of the hypophysis was not possible.
      [68Ga-DOTA]-TATE-Positron-Emission-Tomography was performed, showing somatostatin
      receptor expression of the paranasal lesion but not of the adrenal lesion or the
      hypophysis. The paranasal tumor was resected and found to be an
      adrenocorticotropic hormone-producing paraganglioma of low-proliferative rate.
      Postoperatively the patient became normokaliaemic, normoglycemic and normotensive
      without further need for medication. Genetic testing showed no mutation of the
      succinatdehydrogenase subunit B- and D genes, thus excluding hereditary
      paragangliosis. CONCLUSION: Detection of the adrenocorticotropic hormone source
      in Cushing's syndrome can prove extremely challenging, especially when commonly
      used imaging modalities are unavailable or inconclusive. The present case was
      further complicated by the simultaneous detection of two tumorous lesions of
      initially unclear biochemical behaviour. In such cases, novel diagnostic tools -
      such as somatostatin-receptor imaging - can prove useful in localising hormonally
      active neuroendocrine tissue. The clinical aspects of the case are discussed and
      relevant literature is reviewed.

PMID- 23958172
TI  - Calcaneal bone mineral density in young adults prescribed selective serotonin
      reuptake inhibitors.
AB  - BACKGROUND: Several previous studies have reported both an association between
      selective serotonin reuptake inhibitors (SSRI) and decreased bone mineral density
      and increased fractures, but no previous studies have specifically evaluated bone
      health in young adults who have a history of SSRI use. OBJECTIVE: The purpose was
      to characterize the effect SSRI use in early adulthood on bone mineral density.
      METHODS: A cross-sectional study was conducted on subjects who voluntarily
      responded to recruitment methods for the study. Young adults aged 18 to 25 years
      who were currently or had previously taken an SSRI for a minimum of 3 consecutive
      months were included in the study. A subject interview was conducted on each
      patient to collect background information. Each subject's calcaneal bone mineral
      density was then measured with an ultrasonometer. RESULTS: Complete data were
      collected on 51 subjects. The median duration of SSRI use was 24 +/- 54 months. A
      significant negative correlation was observed between SSRI duration and calcaneal
      ultrasound T-score (r = -0.53, P < 0.001) which was unchanged in depressed
      subjects. Subjects on continuous SSRIs for >24 months had a significantly lower
      median T-score (0.30 +/- 0.93) than subjects taking SSRIs for <= 24 months (0.90
      +/- 0.81; P = 0.0010). CONCLUSIONS: In this young relatively healthy population
      who were following most of the recommendations to improve bone health, a
      significant negative correlation was observed between the duration of SSRI use
      and bone mineral density. Subjects who were on SSRIs for longer than 24 months
      had a significantly lower T-score. Further large scale longitudinal studies are
      needed in this younger population to determine the effects of chronic SSRI use on
      bone health.

PMID- 23958173
TI  - Perspectives on the role of stakeholders in knowledge translation in health
      policy development in Uganda.
AB  - BACKGROUND: Stakeholder roles in the application of evidence are influenced by
      context, the nature of the evidence, the policy development process, and
      stakeholder interactions. Past research has highlighted the role of stakeholders
      in knowledge translation (KT) without paying adequate attention to the
      peculiarities of low-income countries. Here we identify the roles, relations, and
      interactions among the key stakeholders involved in KT in Uganda and the
      challenges that they face. METHODS: This study employed qualitative approaches to
      examine the roles of and links among various stakeholders in KT. In-depth
      interviews were conducted with 21 key informants and focused on the key actors in
      KT, their perceived roles, and challenges. RESULTS: Major stakeholders included
      civil society organizations with perceived roles of advocacy, community
      mobilization, and implementation. These stakeholders may ignore unconvincing
      evidence. The community's role was perceived as advocacy and participation in
      setting research priorities. The key role of the media was perceived as knowledge
      dissemination, but respondents noted that the media may misrepresent evidence if
      it is received in a poorly packaged form. The perceived roles of policy makers
      were evidence uptake, establishing platforms for KT and stewardship; negative
      roles included ignoring or even misrepresenting evidence that is not in their
      favor. The roles of parliamentarians were perceived as advocacy and community
      mobilization, but they were noted to pursue objectives that may not be supported
      by the evidence. The researchers' main role was defined as evidence generation,
      but focusing disproportionately on academic interests was cited as a concern. The
      donors' main role was defined as funding research and KT, but respondents were
      concerned about the local relevance of donor-supported research. Respondents
      reported that links among stakeholders were weak due to the absence of
      institutionalized, inclusive platforms. Challenges facing the stakeholders in the
      process of KT were identified. CONCLUSIONS: Our investigation revealed the need
      to consider the roles that various stakeholders are best placed to play. Links
      and necessary platforms must be put in place to achieve synergy in KT. Relevant
      capacities need to be built to overcome the challenges faced by the various
      stakeholders.

PMID- 23958174
TI  - Oral Candida carriage among individuals chewing betel-quid with and without
      tobacco.
AB  - OBJECTIVE: The aim was to assess oral Candida carriage among individuals chewing
      betel-quid (BQ) with and without tobacco. STUDY DESIGN: A retrospective and
      comparative study of oral Candida carriage among individuals chewing BQ with and
      without tobacco. Oral yeast samples were collected from 103 BQ-chewers (52
      chewing BQ with tobacco and 51 chewing BQ without tobacco) and 100 non-chewers.
      Candida strains were cultured in Sabouraud dextrose agar and identified using the
      API 32-C System and polymerase chain reaction-DNA sequencing. Tongue lesions were
      clinically identified and numbers of missing teeth were recorded. Unstimulated
      whole salivary flow rate was recorded. RESULTS: Oral Candida species were
      isolated from 72.7% BQ-chewers (73.1% in individuals chewing BQ with tobacco and
      72.4% in individuals chewing BQ without tobacco) and 61% non-chewers. CONCLUSION:
      Chewing BQ (with or without tobacco) does not influence oral Candida carriage.

PMID- 23958175
TI  - Minimal incision laparoscopy assisted open pediatric pyeloplasty.
AB  - Minimal incision laparoscopy-assisted open pyeloplasty (MILAP) incorporates
      elements of open pyeloplasty (OP) and single incision laparoscopy to improve
      technical ease and cosmetic outcomes. Six MILAP procedures were performed using a
      single transumbilical incision through which the ureteropelvic junction (UPJ) is
      mobilized with standard laparoscopic instrumentation. The UPJ is brought
      extracorporeally through a 1-cm flank incision, and a traditional Anderson-Hynes
      open pyeloplasty is performed. Compared with OP, perioperative outcomes were
      similar. Follow-up renal scans all showed improvement of obstruction. A 1-cm
      flank incision is the only obvious scar. 

PMID- 23958176
TI  - [ICU acquired neuromyopathy].
AB  - ICU acquired neuromyopathy (IANM) is the most frequent neurological pathology
      observed in ICU. Nerve and muscle defects are merged with neuromuscular junction
      abnormalities. Its physiopathology is complex. The aim is probably the
      redistribution of nutriments and metabolism towards defense against sepsis. The
      main risk factors are sepsis, its severity and its duration of evolution. IANM is
      usually diagnosed in view of difficulties in weaning from mechanical ventilation,
      but electrophysiology may allow an earlier diagnosis. There is no curative
      therapy, but early treatment of sepsis, glycemic control as well as early
      physiotherapy may decrease its incidence. The outcomes of IANM are an increase in
      morbi-mortality and possibly long-lasting neuromuscular abnormalities as far as
      tetraplegia. 

PMID- 23958177
TI  - [An unusual case of tension pneumoperitoneum causing subcutaneous emphysema,
      tension pneumothorax and pneumomediastinum after laparoscopic hysterectomy].

PMID- 23958178
TI  - [Evaluation of stress among emergency staff: survey in a Tunisian emergency
      department].
AB  - OBJECTIVES: The objectives of this work were to make an inventory of the stress
      level, to detect various stressors and to describe the working conditions as
      perceived by staff to pinpoint the factors that might be changed. STUDY DESIGN:
      This survey was conducted from July to August 2012 in all sectors of the
      emergency department. We used the Karasek model. Collected data were demographic
      and professional. RESULTS: We included 107 participants, which represent 61.5% of
      the whole staff. The median age of participants was 30 years with a male
      predominance (66%). Scores found place our sample in the dial of "job strain".
      Only 17.8% of participants were found to be active. No significant correlation
      between gender, marital status, seniority and emergency risk of developing stress
      state was found. Age under 30 years (P=0.04) and low social support by
      supervisors (P=0.02) were predictive of developing stress. Job satisfaction was
      lower among paramedics. In multivariate analysis, they were much more sensitive
      to psychological demands that the doctors. CONCLUSION: This study could be used
      to show the importance of preventing this emotional exhaustion in order to
      improve the quality of health care providers but also the care given in this
      service.

PMID- 23958179
TI  - Prevention of drug delivery disturbances during continuous intravenous infusion:
      an in vitro study on a new multi-lumen infusion access device.
AB  - OBJECTIVE: Stopping and restarting carrier fluid flow and performing simultaneous
      drug infusions can lead to hazardous disturbances in drug delivery. The present
      study was designed to assess in vitro whether using a multi-lumen infusion access
      device could prevent noradrenaline disturbances. STUDY DESIGN: In vitro
      laboratory work. METHODS: Two infusion devices were studied: a standard device
      with a four-port manifold and a 150cm extension line and a nine-lumen infusion
      device (Edelvaiss-Multiline((r))) with eight accesses connected to nine separate
      lumens in a single tube of 150cm: seven accesses connected to seven peripheral
      lumens and one for the carrier fluid access connected to two lumens. Two
      experimental protocols of noradrenaline infusion were made: (a) drug flow rate
      change and (b) stop-and-go carrier fluid flows. Two parameters were studied: drug
      mass flow rate and flow change efficiency (FCE) calculated from the ratio of the
      area under the experimental mass flow rate curve to the area under the
      theoretical instantaneous mass flow rate curve. RESULTS: Variations in
      noradrenaline mass flow rate were more rapid with the Edelvaiss-Multiline((r))
      when the noradrenaline infusion rate was increased or decreased. FCE was
      significantly different from one infusion device to the other during both
      noradrenaline flow rate increase (standard vs. nine-lumen: 58% vs. 84%; P=0.008)
      and decrease (175% vs. 108%; P=0.008). Decreased drug delivery after stopping
      carrier fluid flow (standard vs. nine-lumen: 21% vs. 98%; P=0.008) and sudden
      temporary increases on resumption (253% vs. 103%; P=0.008) were reduced in
      magnitude and duration when using the Edelvaiss-Multiline((r)) with a significant
      difference in FCE between the two infusion devices. CONCLUSIONS: Using the nine
      lumen infusion device reduces drug delivery disturbances during continuous
      intravenous infusion.

PMID- 23958180
TI  - [New oral anticoagulants and emergency procedures].

PMID- 23958181
TI  - Introducing the "Internal Medicine Flashcards": call for papers.

PMID- 23958182
TI  - Transcranial direct current stimulation for generalized anxiety disorder: a case
      study.

PMID- 23958183
TI  - The genome in three dimensions: a new frontier in human brain research.
AB  - Less than 1.5% of the human genome encodes protein. However, vast portions of the
      human genome are subject to transcriptional and epigenetic regulation, and many
      noncoding regulatory DNA elements are thought to regulate the spatial
      organization of interphase chromosomes. For example, chromosomal "loopings" are
      pivotal for the orderly process of gene expression, by enabling distal regulatory
      enhancer or silencer elements to directly interact with proximal promoter and
      transcription start sites, potentially bypassing hundreds of kilobases of
      interspersed sequence on the linear genome. To date, however, epigenetic studies
      in the human brain are mostly limited to the exploration of DNA methylation and
      posttranslational modifications of the nucleosome core histones. In contrast,
      very little is known about the regulation of supranucleosomal structures. Here,
      we show that chromosome conformation capture, a widely used approach to study
      higher-order chromatin, is applicable to tissue collected postmortem, thereby
      informing about genome organization in the human brain. We introduce chromosome
      conformation capture protocols for brain and compare higher-order chromatin
      structures at the chromosome 6p22.2-22.1 schizophrenia and bipolar disorder
      susceptibility locus, and additional neurodevelopmental risk genes, (DPP10,
      MCPH1) in adult prefrontal cortex and various cell culture systems, including
      neurons derived from reprogrammed skin cells. We predict that the exploration of
      three-dimensional genome architectures and function will open up new frontiers in
      human brain research and psychiatric genetics and provide novel insights into the
      epigenetic risk architectures of regulatory noncoding DNA. 

PMID- 23958184
TI  - Evaluating a nurse-led survivorship care package (SurvivorCare) for bowel cancer
      survivors: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Colorectal cancer (CRC) is the most common cancer affecting both men
      and women in Australia. The illness and related treatments can cause distressing
      adverse effects, impact on emotional and psychological well-being, and adversely
      affect social, occupational and relationship functioning for many years after the
      end of treatment or, in fact, lifelong. Current models of follow-up fail to
      address the complex needs arising after treatment completion. Strategies to
      better prepare and support survivors are urgently required. We previously
      developed a nurse-led supportive care program (SurvivorCare) and tested it in a
      pilot study involving 10 CRC survivors. The intervention was found to be highly
      acceptable, appropriate, relevant and useful. METHODS/DESIGN: This study is a
      multisite, randomised controlled trial, designed to assess the impact of the
      addition of the SurvivorCare intervention to usual post-treatment care, for
      people with potentially cured CRC. SurvivorCare comprises the provision of
      survivorship educational materials, a tailored survivorship care plan, an
      individually tailored nurse-led, face-to-face end of treatment consultation and
      three subsequent telephone calls. Eligible patients have completed treatment for
      potentially cured CRC. Other eligibility criteria include stage I to III disease,
      age greater than 18 years and adequate understanding of English. All consenting
      patients complete questionnaires at three time points over a six-month period
      (baseline, two and six months). Measures assess psychological distress, unmet
      needs and quality of life. DISCUSSION: This supportive care package has the
      potential to significantly reduce individual suffering, whilst reducing the
      burden of follow-up on acute cancer services through enhanced engagement with and
      utilisation of general practitioners and community based services. If the
      intervention is successful in achieving the expected health benefits, it could be
      disseminated readily. All training and supporting materials have been developed
      and standardised. Furthermore, the intervention could easily be adapted to other
      cancer or chronic disease settings. TRIAL REGISTRATION: Australian New Zealand
      Clinical Trial Registry ACTRN12610000207011.

PMID- 23958185
TI  - Early innate immunity determines outcome of Mycobacterium tuberculosis pulmonary
      infection in rabbits.
AB  - BACKGROUND: Pulmonary infection of humans by Mycobacterium tuberculosis (Mtb),
      the causative agent of tuberculosis (TB), results in active disease in 5-10% of
      individuals, while asymptomatic latent Mtb infection (LTBI) is established in the
      remainder. The host immune responses that determine this differential outcome
      following Mtb infection are not fully understood. Using a rabbit model of
      pulmonary TB, we have shown that infection with the Mtb clinical isolate HN878 (a
      hyper-virulent W-Beijing lineage strain) leads to progressive cavitary disease
      similar to what is seen in humans with active TB. In contrast, infection with Mtb
      CDC1551 (a hyper-immunogenic clinical isolate) is efficiently controlled in
      rabbit lungs, with establishment of LTBI, which can be reactivated upon treatment
      with immune-suppressive drugs. We hypothesize that the initial interaction of Mtb
      with the cells of the host response in the lungs determine later outcome of
      infection. RESULTS: To test this hypothesis, we used our rabbit model of
      pulmonary TB and infected the animals with Mtb HN878 or CDC1551. At 3 hours, with
      similar lung bacillary loads, HN878 infection caused greater accumulation of
      mononuclear and polymorphonuclear leukocytes (PMN) in the lungs, compared to
      animals infected with CDC1551. Using whole-genome microarray gene expression
      analysis, we delineated the early transcriptional changes in the lungs of HN878-
      or CDC1551-infected rabbits at this time and compared them to the differential
      response at 4 weeks of Mtb-infection. Our gene network and pathway analysis
      showed that the most significantly differentially expressed genes involved in the
      host response to HN878, compared to CDC1551, at 3 hours of infection, were
      components of the inflammatory response and STAT1 activation, recruitment and
      activation of macrophages, PMN, and fMLP (N-formyl-Methionyl-Leucyl
      Phenylalanine)-stimulation. At 4 weeks, the CDC1551 bacillary load was
      significantly lower and the granulomatous response reduced compared to HN878
      infection. Moreover, although inflammation was dampened in both Mtb infections at
      4 weeks, the majority of the differentially expressed gene networks were similar
      to those seen at 3 hours. CONCLUSIONS: We propose that differential regulation of
      the inflammation-associated innate immune response and related gene expression
      changes seen at 3 hours determine the long term outcome of Mtb infection in
      rabbit lungs.

PMID- 23958187
TI  - Proceedings of conference on Mechanism-Based Development of Natural Products for
      Human Health.
AB  - Mechanism-Based Development of Natural Products in Human Health. 

PMID- 23958186
TI  - The phenotype and genotype of rheumatoid arthritis in the Democratic Republic of
      Congo.
AB  - INTRODUCTION: Little is known about rheumatoid arthritis in the black,
      particularly in Congolese, populations. Our objective was to describe the
      phenotype and genotype of rheumatoid arthritis (RA) in Congolese. METHODS: All
      consecutive rheumatoid arthritis (RA) patients attending Kinshasa University
      Hospital in a three-year time period were included. Demographics, clinical
      features and tobacco consumption were noted. Disease Activity Score (DAS)-28
      based on the erythrocyte sedimentation rate (ESR), Health Assessment
      Questionnaire (HAQ), anti-citrullinated peptide antibodies (CCP) antibodies and
      rheumatoid factor (RF) were determined. Radiographs were scored according to
      Sharp-van der Heijde. On a subset of patients and controls HLA-DRB1 typing was
      performed. RESULTS: A total of 114 females and 14 males aged 51.2 +/- 14.9 were
      included. Mean duration of symptoms was four years. Moderate tobacco consumption
      was reported in a minority of patients. DAS-28 at first visit was >5.1 and HAQ
      >=0.5 in all patients. X-rays showed joint erosions and/or joint space narrowing,
      mostly of a moderate grade in 55.8% of patients. Anti-CCP and/or RF were present
      in 48.6% of patients with available data (n = 72) and in 3.0% of controls (n =
      67). Radiographic changes and nodules were more frequent in RF or anti-CCP
      positive patients. One copy of the shared epitope was found in 13 patients
      (35.1%) and 3 controls (12.5%). Two copies were found in one patient (2.7%) and
      in one control (4.2%). CONCLUSION: Congolese patients with RA consult long after
      disease onset. Despite this delay, the majority presents without major damage and
      is RF, anti-CCP and SE negative. We put forward the hypothesis that besides
      different environmental factors there is probably also a particular genetic risk
      profile in Congolese patients, different from the HLA-DRB1 shared epitope.

PMID- 23958188
TI  - Targeting the calmodulin-regulated ErbB/Grb7 signaling axis in cancer therapy.
AB  - Signal transduction pathways essential for the survival and viability of the cell
      and that frequently present aberrant expression or function in tumors are
      attractive targets for pharmacological intervention in human cancers. In this
      short review we will describe the regulation exerted by the calcium-receptor
      protein calmodulin (CaM) on signaling routes involving the family of ErbB
      receptors - highlighting the epidermal growth factor receptor (EGFR/ErbB1) and
      ErbB2 - and the adaptor protein Grb7, a downstream signaling component of these
      receptors. The signaling mechanism of the ErbB/Grb7 axis and the regulation
      exerted by CaM on this pathway will be described. We will present a brief
      overview of the current efforts to inhibit the hyperactivity of ErbB receptors
      and Grb7 in tumors. The currently available information on targeting the CaM
      binding site of these signaling proteins will be analyzed, and the pros and cons
      of directly targeting CaM versus the CaM-binding domain of the ErbB receptors and
      Grb7 as potential anti-cancer therapy will be discussed.

PMID- 23958190
TI  - Strategies for the discovery and development of anti-diabetic drugs from the
      natural products of traditional medicines.
AB  - This review discusses issues largely from the biological point of view about the
      targeted approaches for the use of natural products for the discovery of anti
      diabetic drugs in collaboration with medicinal chemists and computer-aided drug
      design. A major thrust of this review reflects the collaborative research of four
      institutions: RMIT University (Australia), Garvan Institute of Medical Research
      (Australia), Shanghai Institute of Materia Medica of the Chinese Academy of
      Science (China) and Sun-Yat Sen University (China) in the past eight years. By
      joining forces of biomedical research in diabetes and medicinal chemistry with a
      focus on traditional medicine, they are trying to bridge the West (the latest
      research discoveries in biomedical research) with the East (traditional medicine)
      to step forward in drug discovery from natural products.

PMID- 23958189
TI  - Plasma membrane calcium ATPases as novel candidates for therapeutic agent
      development.
AB  - Plasma membrane Ca2+ ATPases (PMCAs) are highly regulated transporters
      responsible for Ca2+ extrusion from all eukaryotic cells. Different PMCA isoforms
      are implicated in various tasks of Ca2+ regulation including bulk Ca2+ transport
      and localized Ca2+ signaling in specific membrane microdomains. Accumulating
      evidence shows that loss, mutation or inappropriate expression of different PMCAs
      is associated with pathologies ranging from hypertension, low bone density and
      male infertility to hearing loss and cerebellar ataxia. Compared to Ca2+ influx
      channels, PMCAs have lagged far behind as targets for drug development, mainly
      due to the lack of detailed understanding of their structure and specific
      function. This is rapidly changing thanks to integrated efforts combining
      biochemical, structural, cellular and physiological studies suggesting that
      selective modulation of PMCA isoforms may be of therapeutic value in the
      management of different and complex diseases. Both structurally informed rational
      design and high-throughput small molecule library screenings are promising
      strategies that are expected to lead to specific and isoform-selective modulators
      of PMCA function. This short review will provide an overview of the diverse roles
      played by PMCA isoforms in different cells and tissues and their emerging
      involvement in pathophysiological processes, summarize recent progress in
      obtaining structural information on the PMCAs, and discuss current and future
      strategies to develop specific PMCA inhibitors and activators for potential
      therapeutic applications.

PMID- 23958191
TI  - Optimisation and validation of a high throughput screening compatible assay to
      identify inhibitors of the plasma membrane calcium ATPase pump--a novel
      therapeutic target for contraception and malaria.
AB  - PURPOSE: ATPases, which constitute a major category of ion transporters in the
      human body, have a variety of significant biological and pathological roles.
      However, the lack of high throughput assays for ATPases has significantly limited
      drug discovery in this area. We have recently found that the genetic deletion of
      the ATP dependent calcium pump PMCA4 (plasma membrane calcium/calmodulin
      dependent ATPase, isoform 4) results in infertility in male mice due to a
      selective defect in sperm motility. In addition, recent discoveries in humans
      have indicated that a single nucleotide polymorphism (SNP) in the PMCA4 gene
      determines the susceptibility towards malaria plasmodium infection. Therefore,
      there is an urgent need to develop specific PMCA4 inhibitors. In the current
      study, we aim to optimise and validate a high throughput screening compatible
      assay using recombinantly expressed PMCA4 and the HTRF(r) Transcreener(r) ADP (TR
      FRET) assay to screen a drug library. METHODS AND RESULTS: PMCA4 membrane
      microsomes were prepared from HEK293 cells overexpressing PMCA4. Western blot
      quantification revealed nearly nine-fold increased expression of PMCA4 compared
      to LacZ (control virus)-infected cells. Maximal PMCA4 microsomal activity was
      achieved in the TR-FRET assay with 15ng/MUl microsomal concentration, 30-minute
      pre-incubation with compounds at 37 degrees C, and calcium buffering with 1mM
      EGTA providing 1MUM free-calcium. Finally a dose-response curve for carboxyeosin
      (a non-specific PMCA inhibitor) under optimised conditions showed significant
      PMCA4 inhibition. Upon confirmation that the assay was suitable for high
      throughput screening, we have screened the ChemBioNet small molecule library
      (~21,000 compounds) against the PMCA4 assay to identify those that are its
      apparent inhibitors. This screening yielded 1,494 primary hits. CONCLUSIONS: We
      have optimised the HTRF(r) Transcreener(r) ADP assay for high-throughput
      screening to identify PMCA4 inhibitors. The output of the screening campaign has
      provided preliminary chemical starting points that could be further developed to
      specific PMCA4 inhibitors for non-hormonal contraception or anti-malaria therapy.

PMID- 23958192
TI  - Profiles of surface mosaics on chronic lymphocytic leukemias distinguish stable
      and progressive subtypes.
AB  - PURPOSE: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease, some
      patients may survive for many years, while 20-30% of patients progress and may
      die within several years. Currently, there is not a single procedure that enables
      accurate prognosis and triaging of those patients who need immediate and
      aggressive treatment. All CLL cells are characterised by the expression of the B
      cell antigens CD19, CD20, CD21, CD22 and CD23, with aberrant expression of the T
      cell antigen CD5. METHODS: We have developed a CD antibody microarray (DotScan)
      containing 182 immobilised CD antibodies that has been used to obtain extensive
      surface profiles of CLL cells obtained from 96 patients. RESULTS: Of these 182
      antigens, 27 were significantly differentially expressed between stable, stable
      progressive and progressive CLL. Some of these antigens are not expressed on
      normal B-cells and may be targets for therapeutic antibodies against CLL.
      Unsupervised hierarchical clustering of the surface profiles from 96 patients
      showed that those with progressive CLL could be distinguished based solely upon
      this 'disease signature'. The sensitivity (proportion of actual positives
      correctly identified) was 67.9%, the specificity (proportion of negatives
      correctly identified) was 77.5%, and the accuracy was 71.9%. CONCLUSIONS:
      Considerable effort by a number of research groups has resulted in identification
      of individual markers for progressive CLL, but their collective use is yet to
      provide a test that identifies CLL patients at risk. Data presented here provide
      a basis for development of a simple test using an antibody microarray.

PMID- 23958193
TI  - Cell-derived microparticles: new targets in the therapeutic management of
      disease.
AB  - Intercellular communication is essential to maintain vital physiological
      activities and to regulate the organism's phenotype. There are a number of ways
      in which cells communicate with one another. This can occur via autocrine
      signaling, endocrine signaling or by the transfer of molecular mediators across
      gap junctions. More recently communication via microvesicular shedding has gained
      important recognition as a significant pathway by which cells can coordinate the
      spread and dominance of selective traits within a population. Through this
      communication apparatus, cells can now acquire and secure a survival advantage,
      particularly in the context of malignant disease. This review aims to highlight
      some of the functions and implications of microparticles in physiology of various
      disease states, and present a novel therapeutic strategy through the regulation
      of microparticle production.

PMID- 23958194
TI  - Examining the cognitive effects of a special extract of Bacopa monniera (CDRI08:
      Keenmnd): a review of ten years of research at Swinburne University.
AB  - Bacopa monniera (EBm), an Indian aquatic herb, has been used in traditional
      Ayurvedic medicine for centuries for indications related to memory and
      inflammation. More recently specific extracts of EBm have emerged that have been
      subjected to rigorous in vitro, animal and now human clinical trials. In this
      paper we discuss some of these studies with special reference to mechanisms and
      efficacy of a special extract of Bacopa (CDRI08). Studies using this extract
      indicate that CDRI08 has several modes of action on the human brain. Promising
      indications for use in humans include improving cognition in the elderly and in
      patients with neurodegenerative disorders.

PMID- 23958195
TI  - Learning from both sides: Experiences and opportunities in the investigation of
      Australian aboriginal medicinal plants.
AB  - With one of the oldest surviving cultures in the world, Australian Aboriginal
      people have developed immense knowledge about the diverse Australian flora.
      Western scientific investigation of some Australian Aboriginal medicinal plants
      has demonstrated interesting pharmacological activities and chemistry, however
      the majority of these species have not yet been extensively examined. We argue
      that research that is locally initiated and driven by Indigenous traditional
      owners in collaboration with Western scientists has significant potential to
      develop new plant-based products. Locally driven medicinal plants research in
      which traditional owners work as researchers in collaboration with University
      based colleagues in the investigation of medicines rather than "stakeholders" or
      "informants" is one model that may be used in characterising plants with the
      potential to be developed into sustainable plant-based medicinal products with
      commercial value. Our team has taken this approach in research located both on
      traditional homelands and in the laboratory. Research being conducted by the
      University of South Australia and Chuulangun Aboriginal Corporation has led to
      patent filing for protection of intellectual property associated with novel
      compounds and extracts with the potential for development through cosmetic,
      complementary medicine and pharmaceutical routes. Ongoing research is examining
      the commercial developmental pathways and requirements for product development in
      these spaces. This review will address the opportunities that might exist for
      working in partnership with Australian Indigenous communities, some of the
      scientific knowledge which has been generated so far from our work together and
      the lessons learnt since the inception of the collaboration between the
      Chuulangun Aboriginal Corporation and scientists from the University of South
      Australia.

PMID- 23958196
TI  - Quantification of three chiral flavonoids with reported bioactivity in selected
      licensed Canadian natural health products and US marketed dietary supplements.
AB  - PURPOSE: Research indicating potentially beneficial bioactivity of flavonoids has
      produced a market and demand for natural health products and dietary supplements
      containing flavonoids. Implementation of the Canadian natural health product
      (NHP) regulations in January of 2004 increased regulation and oversight of NHP
      manufacture and marketing leading many consumers and clinicians to assume a
      similar pathway of development and approval to over-the-counter or prescription
      drugs. METHODS: Three stereospecific liquid chromatograph/mass spectrometry
      (LC/MS) methods were used to assess the flavonoids, liquiritigenin, pinocembrin,
      and pinostrobin, in selected Canadian licensed NHP's and US marketed dietary
      supplements. RESULTS: The present study quantifies bioactive flavonoids in these
      products and notes variability in flavonoid content. CONCLUSIONS: Efficacy and
      safety of NHP's and dietary supplements should not be assumed due to differences
      in criteria for NHP licensure by Health Canada as well as variation of flavonoid
      content between manufacturers and products with similar indications for use.

PMID- 23958197
TI  - The antiinflammatory action and pharmacokinetics of a novel glucosamine-based di
      peptide aminosugar.
AB  - PURPOSE: We have previously shown favorable in vitro gut permeability for three
      novel di-peptide esters of glucosamine (GlcN) likely facilitated by the peptide
      transporter 1 (PepT1). Herein, we report the development of a novel assay for the
      determination of bioavailability of the peptide ester of interest, the anti
      inflammatory properties of a glycine-valine ester derivative of GlcN (GVG) as
      well as its pharmacokinetics under healthy and inflammatory conditions. METHODS:
      A pre-column derivatization (with 9-fluorenylmethoxycarbonyl) HPLC assay was
      developed to study bioavailability of GVG, GlcN or cleaved GlcN in the rats that
      were cannulated in their right jugular vein for blood collection. The compounds
      of interest were orally administered to both healthy and arthritic rats. Serial
      blood samples and urine were collected and assayed for the compounds. The
      stability of the GVG was also tested after incubation with the rat feces.
      Efficacy of GVG was tested in inflamed rats (injection of 0.2 mL of Mycobacterium
      butyricum in squalene) following GVG (20 and 30 mg/kg/day GlcN equivalent) or
      GlcN (20 and 90 mg/kg/day) administration. Arthritis index was calculated at the
      end of the experiment. RESULTS: The assay was linear (ranged between 0.05-20
      MUg/mL) and reproducible (intra- and inter-day<10%). Among the tested compounds,
      only GVG showed a significantly higher plasma concentrations and urinary
      excretion than GlcN (~3-fold increase). GVG showed a favorable stability in the
      rat feces. Adjuvant arthritis was completely prevented with doses greater than 20
      mg/kg/day with GVG being 3-fold more potent than GlcN. CONCLUSION: The examined
      glycine-valine-GlcN di-peptide aminosugar is a potent anti-inflammatory compound
      due to its favorable properties to deliver GlcN into the systemic circulation.

PMID- 23958198
TI  - Cranberry juice ingestion and clinical drug-drug interaction potentials; review
      of case studies and perspectives.
AB  - Cranberry juice is a popular beverage with many health benefits. It has
      anthocyanins to supplement dietary needs. Based on in vitro evidence cranberry
      juice is an inhibitor of CYP enzymes and at higher amounts as potent as
      ketoconazole (CYP3A) and fluconazole (CYP2C9). There is, however, a discrepancy
      between in vitro and in vivo observations with respect to a number of substrates
      (cyclosporine, warfarin, flurbiprofen, tizanidine, diclofenac, amoxicillin,
      ceflacor); with the exception of a single report on midazolam, where there was a
      moderate increase in the AUC of midazolam in subjects pre-treated with cranberry
      juice. However, another study questions the clinical relevancy of in vivo
      pharmacokinetic interaction between cranberry juice and midazolam. The
      controversy may be due to a) under in vitro conditions all anthocyanin principles
      may be available to have a concerted effort in CYP inhibition; however, limited
      anthocyanin principles may be bioavailable with varying low levels in the in vivo
      studies; b) a faster clearance of the active anthocyanin principles under in vivo
      conditions may occur, leading to low threshold levels for CYP inhibition; c)
      efficient protein binding and/or rapid tissue uptake of the substrate may have
      precluded the drug availability to the enzymes in the in vivo studies. With
      respect to pharmacodynamic aspects, while the debate continues on the issue of an
      interaction between warfarin and cranberry juice, the summation of the
      pharmacodynamics data obtained in patients and healthy subjects from different
      prospectively designed and controlled clinical trials does not provide
      overwhelming support for the existence of a pharmacodynamic drug interaction for
      normal cranberry juice ingestion. However, it is apparent that consumption of
      large quantities of cranberry juice (about 1-2 L per day) or cranberry juice
      concentrates in supplements for an extended time period (>3-4 weeks) may
      temporally alter the effect of warfarin. Therefore, the total avoidance of
      cranberry juice by warfarin users may not be warranted by the published studies.
      However, in certain situations of higher intake of cranberry juice or concentrate
      there may be a need to monitor both warfarin doses and its effect.

PMID- 23958199
TI  - (S)-[6]-Gingerol enhances glucose uptake in L6 myotubes by activation of AMPK in
      response to [Ca2+]i.
AB  - PURPOSE: The aim of this study was to investigate the mechanism of (S)-[6]
      gingerol in promoting glucose uptake in L6 skeletal muscle cells. METHODS: The
      effect of (S)-[6]-gingerol on glucose uptake in L6 myotubes was examined using 2
      [1,2-3H]-deoxy-D-glucose. Intracellular Ca2+ concentration was measured using
      Fluo-4. Phosphorylation of AMPKalpha was determined by Western blotting analysis.
      RESULTS: (S)-[6]-Gingerol time-dependently enhanced glucose uptake in L6
      myotubes. (S)-[6]-Gingerol elevated intracellular Ca2+ concentration and
      subsequently induced a dose- and time-dependent enhancement of threonine172
      phosphorylated AMPKalpha in L6 myotubes via modulation by Ca2+/calmodulin
      dependent protein kinase kinase. CONCLUSION: The results indicated that (S)-[6]
      gingerol increased glucose uptake in L6 skeletal muscle cells by activating AMPK.
      (S)-[6]-gingerol, a major component of Zingiber officinale, may have potential
      for development as an antidiabetic agent.

PMID- 23958200
TI  - Control of neonatal spinal networks by nociceptors: a potential role for TRP
      channel based therapies.
AB  - Pediatric spinal cord injury (SCI) often leads to increased nociceptive input
      resulting in aberrant motor output like tremor and spasticity. Acute plasticity
      within spinal pain and motor networks following pediatric SCI may result in long
      term sensorimotor disabilities. Despite this, pediatric SCI remains poorly
      understood. Part of the problem lies in the paucity of detailed studies aimed at
      defining sensorimotor control by nociceptors during development. This review
      provides an overview of work that highlights afferent control of sensorimotor
      networks by defined nociceptors in the developing spinal cord. Here, we focus on
      the well established and widely used neonatal sensorimotor model called
      sacrocaudal afferent (SCA) pathway. Until recently, the identity of specific
      subclasses of nociceptive afferents in the SCA pathway controlling developing
      sensorimotor networks was unknown. We highlight here the use of members of the
      Transient Receptor Potential (TRP) ion channels and mouse genetics to identify
      specific subsets of nociceptive afferents in the SCA pathway. In addition, we
      highlight the use of mouse genetics to map sensorimotor networks during
      development and potential future applications. A neonatal spinal cord model of
      central neuropathic pain via a defined set of nociceptors is presented as a probe
      into potential therapeutic avenues in neonatal SCI. Finally, knowledge
      translation from neonatal basic research to the pediatric population in the
      clinic is described. In conclusion, studies in neonatal models may lead to
      therapeutic strategies and pharmaceuticals for chronic pain and motor dysfunction
      after SCI during development.

PMID- 23958201
TI  - Determination of aflatoxins in medicinal plants by high-performance liquid
      chromatography-tandem mass spectrometry.
AB  - PURPOSE: The intention of the proposed work is to study the presence of the
      aflatoxins B1, B2, G1 and G2 in medicinal plants, namely Mucuna pruriens,
      Delphinium denudatum and Portulaca oleraceae. METHODOLOGY: The aflatoxins were
      extracted, purified by immunoaffinity column chromatography and analysed by high
      performance liquid chromatography-tandem quadrupole mass spectrometry with
      electrospray ionisation (HPLC-MS/MS). Fungal count was carried out in PDA media.
      RESULTS: A good linear relationship was found for AFB1, AFB2, AFG1 and AFG2 at 1
      10 ppb (r>0.9995). The analyte accuracy under three different spiking levels was
      86.7-108.1 %, with low per cent relative standard deviations in each case. The
      aflatoxins can be separated within 5 to7 min using an Agilent XDB C18-column. We
      found that AFB1 and AFB2 were in trace amounts below the detection limit in M.
      pruriens whilst they were not detected in D. denudatum. P. oleraceae was found to
      be contaminated with AFB1 and AFB2. AFG1 and AFG2 were not detected in M.
      pruriens, P. oleraceae and were below the detection limit in D. denudatum. This
      was consistent with very low numbers of fungal colonies observed after 6 hr of
      incubation. CONCLUSION: The analytical method developed is simple, precise,
      accurate, economical and can be effectively used to determine the aflatoxins in
      medicinal plants and therefore to control the quality of products. The aflatoxin
      levels in the plant extracts examined were related to the minimal fungal load in
      the medicinal plants examined.

PMID- 23958202
TI  - Drug discovery inspired by mother nature: seeking natural biochemotypes and the
      natural assembly rules of the biochemome.
AB  - PURPOSE: The Human Genome Project is producing a new biological 'periodic table',
      which defines all genes for making macromolecules (proteins, DNA, RNA, etc) and
      the relations between genes and their biological functions. We now need to
      consider whether to initiate a biochemome project aimed at discovering
      biochemistry's 'periodic table', which would define all molecular parts for
      making small molecules (natural products) and the relations between the parts and
      their functions to regulate genes. By understanding the Biochemome, we might be
      able to design biofunctional molecules based upon a set of molecular parts for
      drug innovation. METHODS: A number of algorithms for processing chemical
      structures are used to systematically derive chemoyls (natural building blocks)
      from a database of compounds identified in Traditional Chinese Medicine (TCM).
      The rules to combine chemoyls for biological activities are then deduced by
      mining an annotated TCM structure-activity database (ATCMD). Based upon the rules
      and the basic chemoyls, a chemical library can be biochemically profiled, virtual
      synthetic routes can be planned, and lead compounds can be identified for a
      specific drug target. CONCLUSIONS: The Biochemome is the complete set of
      molecular components (chemoyls) in an organism and Biochemomics studies the rules
      governing their assembly and their evolution, together with the relations between
      the Biochemome and drug targets. This approach provides a new paradigm for drug
      discovery that is based on a comprehensive knowledge of the synthetic origins of
      biochemical diversity, and helps to direct biomimetic syntheses aimed at
      assembling quasi-natural product libraries for drug screening.

PMID- 23958203
TI  - Light-to-moderate ethanol feeding augments AMPK-alpha phosphorylation and
      attenuates SREBP-1 expression in the liver of rats.
AB  - PURPOSE: Fatty liver disease, a hepatic manifestation of metabolic syndrome, is
      one of the major causes of chronic liver diseases. Epidemiological studies
      suggest that regular light-to-moderate ethanol consumption lowers the risk of
      developing metabolic disorders including dislipidemia, insulin resistance, type 2
      diabetes and fatty liver disease. However, the mechanism(s) of the protective
      effect of light-to-moderate ethanol consumption on the liver remains unknown.
      METHODS: In the present study, we investigated the effects of light (6%, 0.94
      g/kg/day) and moderate (12%, 1.88 g/kg/day) ethanol feeding in rats for 3 weeks
      on the circulating and hepatic biochemical profiles and on the hepatic protein
      expression and phosphorylation status of adenosine monophosphate-activated
      protein kinase-alpha (AMPK-alpha) and other down-stream targets of this enzyme
      including sterol regulatory element-binding protein-1 (SREBP-1), SREBP cleavage
      activating protein (SCAP) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA
      reductase). RESULTS: Despite no significant difference in food-intake among the
      groups, light ethanol treatment significantly increased the body weight compared
      to control rats. Serum glucose, insulin, total cholesterol, triglycerides,
      phospholipids and hepatic cholesterol and triglycerides were not significantly
      different among the groups. However, serum free fatty acids were significantly
      reduced with light ethanol treatment. Both light and moderate ethanol treatment
      significantly increased the hepatic levels of phosphorylated AMPK-alpha protein
      and this was associated with significant reduction of SREBP-1 protein expression,
      suggesting an enhanced fatty acid oxidation. In addition, light ethanol treatment
      significantly decreased the SCAP protein expression in the liver. However, liver
      HMG-CoA protein expression was not significantly different with ethanol
      consumption. CONCLUSION: Chronic light-to-moderate ethanol consumption increased
      AMPK activation which was associated with decreased expression of SREBP-1 and
      SCAP in the liver. Thus, our studies provide mechanistic evidence for the earlier
      epidemiological studies that indicate light-to-moderate ethanol intake lowers the
      risk of development of fatty liver disease and other metabolic disorders. Our
      studies demonstrate that the protective effects of light-to-moderate ethanol
      arise at least in part by increased phosphorylation of AMPK-alpha and decreased
      SREBP-1 expression in the liver. Further studies are warranted to determine the
      effects of light-to-moderate ethanol on intracellular up-stream and down-stream
      targets of AMPK and also on the implications of light-to-moderate ethanol in
      protecting non-alcoholic fatty liver disease.

PMID- 23958204
TI  - Safranal treatment improves hyperglycemia, hyperlipidemia and oxidative stress in
      streptozotocin-induced diabetic rats.
AB  - PURPOSE: Clinical research has confirmed the efficacy of several plant extracts
      in the modulation of oxidative stress associated with diabetes mellitus. Findings
      indicate that safranal has antioxidant properties. The aim of the present study
      was the evaluation of possible protective effects of safranal against oxidative
      damage in diabetic rats. METHODS: In this study, the rats were divided into the
      following groups of 8 animals each: control, untreated diabetic, three safranal
      (0.25, 0.50, 0.75 mg/kg/day)-treated diabetic groups. Diabetes was induced by
      streptozotocin (STZ) in rats. STZ was injected intraperitoneally at a single dose
      of 60 mg/kg for diabetes induction. Safranal (intraperitoneal injection) was
      administered 3 days after STZ administration; these injections were continued to
      the end of the study (4 weeks). At the end of the 4-week period, blood was drawn
      for biochemical assays. In order to determine the changes of cellular antioxidant
      defense systems, antioxidant enzymes including glutathione peroxidase (GSHPx),
      superoxide dismutase (SOD) and catalase (CAT) activities were measured in serum.
      Moreover we also measured serum nitric oxide (NO) and serum malondialdehyde (MDA)
      levels, a marker of lipid peroxidation. RESULTS: STZ-induced diabetes caused an
      elevation (p < 0.001) of blood glucose, MDA, NO, total lipids, triglycerides and
      cholesterol, with reduction of GSH level and CAT and SOD activities. The results
      indicated that the significant elevation in the blood glucose, MDA, NO, total
      lipids, triglycerides, cholesterol and reduction of glutathione level and CAT and
      SOD activity were ameliorated in the safranal-treated diabetic groups compared
      with the untreated groups, in a dose dependent manner (p < 0.05, p<0.01, p <
      0.001). CONCLUSION: These results suggest that safranal has antioxidant
      properties and improves chemically-induced diabetes and its complications by
      modulation of oxidative stress.

PMID- 23958205
TI  - A longitudinal survey of African animal trypanosomiasis in domestic cattle on the
      Jos Plateau, Nigeria: prevalence, distribution and risk factors.
AB  - BACKGROUND: Trypanosomiasis is a widespread disease of livestock in Nigeria and a
      major constraint to the rural economy. The Jos Plateau, Nigeria was free from
      tsetse flies and the trypanosomes they transmit due to its high altitude and the
      absence of animal trypanosomiasis attracted large numbers of cattle-keeping
      pastoralists to inhabit the plateau. The Jos Plateau now plays a significant role
      in the national cattle industry, accommodating approximately 7% of the national
      herd and supporting 300,000 pastoralists and over one million cattle. However,
      during the past two decades tsetse flies have invaded the Jos Plateau and animal
      trypanosomiasis has become a significant problem for livestock keepers. METHODS:
      In 2008 a longitudinal two-stage cluster survey on the Jos Plateau. Cattle were
      sampled in the dry, early wet and late wet seasons. Parasite identification was
      undertaken using species-specific polymerase chain reactions to determine the
      prevalence and distribution bovine trypanosomiasis. Logistic regression was
      performed to determine risk factors for disease. RESULTS: The prevalence of
      bovine trypanosomiasis (Trypanosoma brucei brucei, Trypanosoma congolense
      savannah, Trypanosoma vivax) across the Jos Plateau was found to be high at 46.8%
      (39.0 - 54.5%) and significant, seasonal variation was observed between the dry
      season and the end of the wet season. T. b. brucei was observed at a prevalence
      of 3.2% (1% - 5.5%); T. congolense at 27.7% (21.8% - 33.6%) and T. vivax at 26.7%
      (18.2% - 35.3%). High individual variation was observed in trypanosomiasis
      prevalence between individual villages on the Plateau, ranging from 8.8% to
      95.6%. Altitude was found to be a significant risk factor for trypanosomiasis
      whilst migration also influenced risk for animal trypanosomiasis. CONCLUSIONS:
      Trypanosomiasis is now endemic on the Jos Plateau showing high prevalence in
      cattle and is influenced by seasonality, altitude and migration practices.
      Attempts to successfully control animal trypanosomiasis on the Plateau will need
      to take into account the large variability in trypanosomiasis infection rates
      between villages, the influence of land use, and husbandry and management
      practices of the pastoralists, all of which affect the epidemiology of the
      disease.

PMID- 23958206
TI  - The Care Process Self-Evaluation Tool: a valid and reliable instrument for
      measuring care process organization of health care teams.
AB  - BACKGROUND: Patient safety can be increased by improving the organization of
      care. A tool that evaluates the actual organization of care, as perceived by
      multidisciplinary teams, is the Care Process Self-Evaluation Tool (CPSET). CPSET
      was developed in 2007 and includes 29 items in five subscales: (a) patient
      focused organization, (b) coordination of the care process, (c) collaboration
      with primary care, (d) communication with patients and family, and (e) follow-up
      of the care process. The goal of the present study was to further evaluate the
      psychometric properties of the CPSET at the team and hospital levels and to
      compile a cutoff score table. METHODS: The psychometric properties of the CPSET
      were assessed in a multicenter study in Belgium and the Netherlands. In total,
      3139 team members from 114 hospitals participated. Psychometric properties were
      evaluated by using confirmatory factor analysis (CFA), Cronbach's alpha,
      interclass correlation coefficients (ICCs), Kruskall-Wallis test, and Mann
      Whitney test. For the cutoff score table, percentiles were used. Demographic
      variables were also evaluated. RESULTS: CFA showed a good model fit: a normed fit
      index of 0.93, a comparative fit index of 0.94, an adjusted goodness-of-fit index
      of 0.87, and a root mean square error of approximation of 0.06. Cronbach's alpha
      values were between 0.869 and 0.950. The team-level ICCs varied between 0.127 and
      0.232 and were higher than those at the hospital level (0.071-0.151). Male team
      members scored significantly higher than females on 2 of the 5 subscales and on
      the overall CPSET. There were also significant differences among age groups.
      Medical doctors scored significantly higher on 4 of the 5 subscales and on the
      overall CPSET. Coordinators of care processes scored significantly lower on 2 of
      the 5 subscales and on the overall CPSET. Cutoff scores for all subscales and the
      overall CPSET were calculated. CONCLUSIONS: The CPSET is a valid and reliable
      instrument for health care teams to measure the extent care processes are
      organized. The cutoff table permits teams to compare how they perceive the
      organization of their care process relative to other teams.

PMID- 23958207
TI  - PLCE and the RASSF family in tumour suppression and other functions.
AB  - Not all proteins implicated in direct binding to Ras appear to have a positive
      role in the generation and progression of tumours; examples include Phospholipase
      C epsilon (PLCE) and some members of the Ras-association domain family (RASSF).
      The RASSF family comprises of ten members, known as RASSF1 to RASSF10. PLCE and
      RASSF members carry a common Ras-association domain (RA) that can potentially
      bind Ras oncoproteins and mediate Ras-regulated functions. RASSF1 to RASSF6 also
      share a common SARAH domain that facilitates protein-protein interactions with
      other SARAH domain proteins. The majority of the family are frequently
      downregulated by epigenetic silencing in cancers. They are implicated in various
      important biological processes including apoptosis, microtubule stabilisation and
      cell cycle regulation. Recent studies have reinforced the tumour suppressive
      properties of the RASSF family, with new evidence of emerging pathways and novel
      functions that suggest a wider role for these proteins. This review will first
      describe an emerging role of PLCE in tumour suppression and then focus on and
      summarise the new findings on the RASSF family in the last five years to
      consolidate their well-established functions, and highlight the new regulatory
      roles of specific RASSF members. 

PMID- 23958208
TI  - Nutrition educator adoption and implementation of an experiential foods
      curriculum.
AB  - OBJECTIVE: Describe changes in Nutrition Educator (NE) and Extension Agent (EA)
      motivation, self-efficacy, and behavioral capability over time after experiential
      food tasting curriculum training. Identify promoters of curriculum adoption,
      implementation, and future use. DESIGN: Mixed methods design including surveys,
      lesson implementation reports, and interviews. SETTING: New Mexico limited
      resource schools. PARTICIPANTS: Convenience sample of New Mexico Extension NE (n
      = 42) and their EA supervisors (n = 21). INTERVENTION: Three-hour curriculum
      training employing Social Cognitive Theory and Diffusion of Innovations. MAIN
      OUTCOME MEASURES: Perceived change in motivation, self-efficacy, and behavioral
      capability from post-training through 8-month post-training; promoters and
      challenges to curriculum adoption, implementation, and future use. ANALYSIS:
      Repeated-measures ANOVA analyzed perceived behavior change over time.
      Significance was set at P <= .05. Qualitative responses were categorized by
      theme. RESULTS: Gains in NE motivation, self-efficacy, and behavioral capability
      were sustained at 8 months post-training. High adoption/implementation rates
      (79%) were attributed to strong implementation expectations, observational
      learning, experiential training elements, and perceived curriculum compatibility.
      Environmental factors including time constraints, personnel turnover, and
      scheduling conflicts proved challenging. CONCLUSIONS AND IMPLICATIONS: Maximizing
      curriculum simplicity and compatibility and incorporating behavioral capability,
      observational learning, and expectations into training support adoption and use.
      Adaptations and techniques to problem-solve challenges should be provided to new
      curricula implementers.

PMID- 23958209
TI  - [Clinical features, care pathways and behaviors of patients with high level of
      cardiovascular risk: transversal study in south-west region of France].
AB  - INTRODUCTION: To screen and to follow-up the patients with high cardiovascular
      risk in general practice may amplify the decrease of the cardiovascular morbi
      mortality observed since a few years. The objective of this study is to identify
      the patients with high cardiovascular risk and to describe the management of
      these patients by general practitioners in Aquitaine. METHODS: Transversal study
      of a sample of patients from 18 to 70 years old with high cardiovascular risk
      (combining at least 3 factors), included by voluntary general practitioners (GP).
      RESULTS: Forty-seven GP included 102 patients, presenting on average 3.7 risk
      factors among which 2.6 modifiable. The target values were reached for 59 % of
      patients with high blood pressure, 56 % of patients with diabetes and 53 % of
      patients with high cholesterol level. The analysis of care pathways identified
      the cardiologist as the privileged interlocutor. The doctors thought that seven
      patients out of 10 could change their risk behaviors. For the patients, the scale
      of declared importance to change was 6.6 on 10 for tobacco, 6.0 for food habits
      and 6.2 for physical activity. The confidence in their capacity to change was 3.8
      on 10 for the tobacco, 5.2 for the food habits and 4.7 for the physical activity.
      DISCUSSION: Although doctors' sample is not representative, these results give an
      original overview of the management of patients with high cardiovascular risk and
      their care pathways. Medical treatments were globally in accordance with
      guidelines. The difficulty to change risk behaviors illustrates the necessity of
      patient therapeutic education.

PMID- 23958210
TI  - [Morbidity and mortality conference in general practice: about an experiment in
      Rhone-Alpes].
AB  - A morbidity and mortality conference (MMC) is a collective analysis,
      retrospective and systemic cases marked by occurrence of death, complication, or
      event that could cause harm to patient (adverse event). OBJECTIVES: Its aim is
      the implementation and monitoring of actions to improve the care of patients and
      patient safety. A group for analysis of adverse events in general practice was
      created in 2011 in the Rhone-Alps, in order to test the feasibility of a MMC with
      general practitioners (GPs). METHOD: A charter setting out the ethical framework
      and the terminology, methodology and the role of individual players was drafted.
      Then a group of volunteers was created among the members of an association of
      continuing medical education. Each session has been the subject of a report. The
      evaluation was conducted through interviews with participants, and with an
      electronic survey of satisfaction. RESULTS: Since 2011, 12 physicians
      participated, analysing 36 cases during seven sessions. Reported events were most
      frequently interested women with a mean age of patients being 48 years (median 46
      years). The situations reported were mixed (error diagnostic, therapeutic,
      adverse drug). Failures are related to care protocols, decision-making, the care
      environment (frequent disruptive pop) and human factors (caregiver stress). The
      participants were satisfied with the initiative. Analyses revealed some redundant
      causes that can be corrected to secure care. Beyond the non-stigmatising approach
      it may allow doctors to discuss their feelings without making them feel guilty
      (concept of second victim). CONCLUSION: If such initiatives are still not
      widespread in ambulatory, they should be promoted by organizations. Openness to
      other caregivers in Ambulatory is a fundamental change desired by the GP. The
      National Programme for Patient Safety recently published in February 2013
      mentions these aspects, emphasizing the key role of the DPC for acquisition
      techniques analysis of the causes by caregivers.

PMID- 23958211
TI  - [Professional consequences of systemic sclerosis].
AB  - Work disability is a major issue in patients with systemic sclerosis (SSc) and
      seems to be substantially higher than other connective tissue diseases. Working
      ability results from complex interactions between factors related to socio
      demographic characteristics, SSc specificities and working conditions. Working
      ability is related to global disability, altered hand function, fatigue, pain,
      type of work and opportunities to adapt workstation. Work disability is
      responsible for reduced income in patients with SSc. 

PMID- 23958212
TI  - Mechanisms of spindle positioning: cortical force generators in the limelight.
AB  - Correct positioning of the spindle governs placement of the cytokinesis furrow
      and thus plays a crucial role in the partitioning of fate determinants and the
      disposition of daughter cells in a tissue. Converging evidence indicates that
      spindle positioning is often dictated by interactions between the plus-end of
      astral microtubules that emanate from the spindle poles and an evolutionary
      conserved cortical machinery that serves to pull on them. At the heart of this
      machinery lies a ternary complex (LIN-5/GPR-1/2/Galpha in Caenorhabditis elegans
      and NuMA/LGN/Galphai in Homo sapiens) that promotes the presence of the motor
      protein dynein at the cell cortex. In this review, we discuss how the above
      components contribute to spindle positioning and how the underlying mechanisms
      are precisely regulated to ensure the proper execution of this crucial process in
      metazoan organisms. 

PMID- 23958213
TI  - Introduction.

PMID- 23958214
TI  - Skin cancer: an overview of epidemiology and risk factors.
AB  - OBJECTIVES: To provide a general overview of malignant melanoma and non-melanoma
      skin cancer, with an emphasis on epidemiology, clinical presentation, and the
      multiple and varied risk factors associated with skin cancer. DATA SOURCES: Peer
      reviewed journal articles, government health reports, book chapters, and Web
      based resources. CONCLUSION: Skin cancer is the most common carcinoma, affecting
      millions worldwide. Incidence is increasing yearly, making it a pre-eminent
      public health threat. Myriad factors increase the risk of skin cancer and may
      serve as important prognostic indicators for the disease. IMPLICATIONS FOR
      NURSING PRACTICE: To provide nurses with a clearer understanding of the causative
      mechanisms of skin cancer and an improved awareness of the risk factors
      associated with the disease.

PMID- 23958215
TI  - Advances in skin cancer early detection and diagnosis.
AB  - OBJECTIVES: To provide an overview of 1) traditional methods of skin cancer early
      detection, 2) current technologies for skin cancer detection, and 3) evolving
      practice models of early detection. DATA SOURCES: Peer-reviewed databased
      articles and reviews, scholarly texts, and Web-based resources. CONCLUSION: Early
      detection of skin cancer through established methods or newer technologies is
      critical for reducing both skin cancer mortality and the overall skin cancer
      burden. IMPLICATIONS FOR NURSING PRACTICE: A basic knowledge of recommended skin
      examination guidelines and risk factors for skin cancer, traditional methods to
      further examine lesions that are suspicious for skin cancer and evolving
      detection technologies can guide patient education and skin inspection decisions.

PMID- 23958216
TI  - Management of non-melanoma skin cancer.
AB  - OBJECTIVES: To review types of, and treatment for, non-melanoma skin cancer
      (NMSC): basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and less
      common NMSC. DATA SOURCES: Standards of care, dermatology texts, peer-reviewed
      journals. CONCLUSION: BCC grows slowly and rarely metastasizes; some BCC subtypes
      can be aggressive and destructive. Early treatment of SCC is usually successful;
      untreated SCC will penetrate underlying tissue, invade lymph nodes, and
      metastasize. Treatment options for NMSC are based on patient and tumor
      characteristics, which determine whether a lesion is low or high risk for cancer
      recurrence after treatment. IMPLICATIONS FOR NURSING PRACTICE: Nurses are
      integral for educating patients about measures to prevent new skin cancers and
      for monitoring for recurrence of NMSC.

PMID- 23958217
TI  - Management of primary cutaneous and metastatic melanoma.
AB  - OBJECTIVES: To review the diagnosis, staging, and treatments (both standard and
      novel) for advanced melanoma and discuss the nursing role in the care of patients
      with melanoma. DATA SOURCES: Published research and education articles, on-line
      journals, recent texts, and references from pertinent articles. CONCLUSION: Most
      melanomas are diagnosed at early localized stages when surgery alone can be
      curative. For patients diagnosed with metastatic disease, treatment options have
      been limited and generally considered ineffective. Recent developments in tumor
      genetics and a greater understanding of the role of the immune system in cancer
      have translated to better treatments. IMPLICATIONS FOR NURSING PRACTICE: Nurses
      play a key role in ensuring that patients with melanoma understand their
      diagnosis, treatment recommendations (including supportive care, palliative
      chemotherapy, immunotherapies), and participation in clinical trials.

PMID- 23958218
TI  - Skin cancer: a growing health problem for children.
AB  - OBJECTIVES: To explore childhood ultraviolet radiation exposure and skin
      carcinogenesis, review prevention practices, analyze indoor tanning trends,
      identify skin cancer prevention programs, and address the role of the oncology
      nurse in youth-focused community initiatives. DATA SOURCES: Review of the
      literature, research, and experience. CONCLUSION: Skin cancer is an important
      health problem for children because it is initiated in childhood and melanoma is
      on the rise in this population. IMPLICATIONS FOR NURSING PRACTICE: Nurses can
      play a pivotal role in reducing the burden of skin cancer through patient
      education, community outreach, and political action.

PMID- 23958219
TI  - Psychological care for people with melanoma: what, when, why and how?
AB  - OBJECTIVES: To provide an update on the psychosocial challenges faced by people
      with melanoma, and ways of addressing barriers to supportive care. DATA SOURCES:
      Refereed journal articles, scholarly texts, monographs. CONCLUSION: Psychological
      needs of people with melanoma frequently go undetected and unmet. Approximately
      30% of all patients diagnosed with melanoma report levels of psychological
      distress, indicating the need for clinical assessment and support. IMPLICATIONS
      FOR NURSING PRACTICE: Psychological interventions using a range of therapeutic
      approaches can improve quality of life and enhance resilience in people with
      melanoma, including reducing anxiety and depression. Nurses can help institute
      and promote supportive care programs that incorporate these interventions.

PMID- 23958220
TI  - Skin cancer preventive behavior and sun protection recommendations.
AB  - OBJECTIVES: To summarize, in tabular form, the current literature and information
      available for skin cancer preventive behaviors and sun protection
      recommendations. DATA SOURCES: Peer-reviewed literature, web sites of
      professional and federal organizations. CONCLUSION: The link between skin cancer
      and ultra-violet radiation (UVR) exposure is well documented. Primary skin cancer
      prevention must focus on proven ways to reduce the amount of UVR that reaches the
      skin, including avoiding UVR, covering up, wearing a wide-brimmed hat and
      sunglasses and use of sunscreen. IMPLICATIONS FOR NURSING PRACTICE: Nurses play a
      key role in patient education and should use evidence-based resources to provide
      skin cancer prevention recommendations.

PMID- 23958222
TI  - Risk assessment for exemptions from ballast water management--the Baltic Sea case
      study.
AB  - The International Convention for the Control and Management of Ship's Ballast
      Water and Sediments sets requirements to prevent organism transfers. Vessels on
      certain routes can be exempted from such requirements based on risk assessment
      (RA). As the convention nears its entry into force, the interest in exemptions
      increases. Such RA should be conducted according to the International Maritime
      Organization G7 Guidelines. We present a RA study for exemptions applied to intra
      Baltic shipping considering different RA methods, i.e., environmental matching,
      species specific method including target species and species biogeographical
      aspects. As reliable species data in the ports considered are unavailable and
      following the precautionary principle, no exemptions should be granted. To ensure
      data reliability, port baseline surveys and regular monitoring programs should be
      undertaken during the exemption period as new species found influence the RA
      result. The RA model prepared is considered as of value to other areas worldwide.

PMID- 23958223
TI  - Formation of the OOH(.) radical at steps of the boehmite surface and its
      inhibition by gallic acid: A theoretical study including DFT-based dynamics.
AB  - The ability of boehmite surface to stabilize reactive oxygen species (ROS) was
      investigated with density functional theory (DFT) calculations. We provide
      evidence that the O2(.-)radical is stabilized at the AlOOH boehmite terrace
      defect-free surface, and that step favors the formation of the OOH(.) radical
      without activation energy required. These tendencies are confirmed when
      considering the explicit presence of water solvent. We propose that gallic acid
      (GA), a non-expensive, non-toxic, natural product and radical scavenger, may form
      a full layer on the (101) stepped boehmite surface. The quenching of O2- to
      OOH(.) reaction on the GA-functionalized boehmite surface is investigated. It is
      shown that gallic acid passivates the surface and that the formation of the
      OOH(.) radical is consequently inhibited. The interaction of the GA
      functionalized boehmite surface with water mimicking the body fluid is also
      investigated by means of DFT-based molecular dynamics simulations at room
      temperature. Hydrogen bonds between the functionalized GA layer and the immediate
      interfacial water are characterized.

PMID- 23958221
TI  - WSG ADAPT - adjuvant dynamic marker-adjusted personalized therapy trial
      optimizing risk assessment and therapy response prediction in early breast
      cancer: study protocol for a prospective, multi-center, controlled, non-blinded,
      randomized, investigator initiated phase II/III trial.
AB  - BACKGROUND: Adjuvant treatment decision-making based on conventional
      clinical/pathological and prognostic single molecular markers or genomic
      signatures is a therapeutic area in which over-/under-treatment are still key
      clinical problems even though substantial and continuous improvement of outcome
      has been achieved over the past decades. Response to therapy is currently not
      considered in the decision-making procedure.ADAPT is one of the first new
      generation (neo)adjuvant trials dealing with individualization of (neo)adjuvant
      decision-making in early breast cancer and aims to establish early predictive
      surrogate markers, e.g., Ki-67, for therapy response under a short induction
      treatment in order to maximally individualize therapy and avoid unnecessary
      toxicity by ineffective treatment. METHODS/DESIGN: The prospective, multi-center,
      controlled, non-blinded, randomized, investigator initiated phase II/III ADAPT
      trial has an innovative "umbrella" protocol design. The "umbrella" is common for
      all patients, consisting of dynamic testing of early therapy response. ADAPT will
      recruit 4,936 patients according to their respective breast cancer subtype in
      four distinct sub-trials at 80 trial sites in Germany; 4,000 patients with
      hormone receptor positive (HR+) and HER2 negative disease will be included in the
      ADAPT HR+/HER2- sub-trial, where treatment decision is based on risk assessment
      and therapy response to induction therapy, and 380 patients will be included in
      ADAPT HER2+/HR+. A further 220 patients will be included in ADAPT HER2+/HR- and
      336 patients will be recruited for ADAPT Triple Negative. These three sub-trials
      focus on identification of early surrogate markers for therapy success in the
      neoadjuvant setting. Patients will be allocated to the respective sub-trial
      according to the result of their diagnostic core biopsy, as reported by
      local/central pathology for HR and HER2 status. DISCUSSION: Recent trials, such
      as the GeparTrio, have shown that response-guided therapy using clinical response
      may improve outcome. For chemotherapy or HER2-targeted treatment, pathologic
      complete response in a neoadjuvant setting is an excellent predictor of outcome.
      For endocrine therapy, response to short induction treatment - as defined by
      decrease in tumor cell proliferation - strongly correlates with outcome. ADAPT
      now aims to combine static prognostic and dynamic predictive markers, focusing
      not just on single therapeutic targets, but also on general markers of
      proliferation and cell death. Biomarker analysis will help to optimize selection
      of subtype-specific treatment. TRIAL REGISTRATION: ClinicalTrials.gov: ADAPT
      Umbrella: NCT01781338; ADAPT HR+/HER2-: NCT01779206; ADAPT HER2+/HR+:
      NCT01745965; ADAPT HER2+/HR-: NCT01817452; ADAPT TN:NCT01815242.

PMID- 23958224
TI  - Water vapour and heat combine to elicit biting and biting persistence in tsetse.
AB  - BACKGROUND: Tsetse flies are obligatory blood feeders, accessing capillaries by
      piercing the skin of their hosts with the haustellum to suck blood. However, this
      behaviour presents a considerable risk as landing flies are exposed to predators
      as well as the host's own defense reactions such as tail flicking. Achieving a
      successful blood meal within the shortest time span is therefore at a premium in
      tsetse, so feeding until replete normally lasts less than a minute. Biting in
      blood sucking insects is a multi-sensory response involving a range of physical
      and chemical stimuli. Here we investigated the role of heat and humidity emitted
      from host skin on the biting responses of Glossina pallidipes, which to our
      knowledge has not been fully studied in tsetse before. METHODS: The onset and
      duration of the biting response of G. pallidipes was recorded by filming
      movements of its haustellum in response to rapid increases in temperature and/or
      relative humidity (RH) following exposure of the fly to two airflows. The
      electrophysiological responses of hygroreceptor cells in wall-pore sensilla on
      the palps of G. pallidipes to drops in RH were recorded using tungsten electrodes
      and the ultra-structure of these sensory cells was studied by scanning and
      transmission electron microscopy. RESULTS: Both latency and proportion of tsetse
      biting are closely correlated to RH when accompanied by an increase of 13.1
      degrees C above ambient temperature but not for an increase of just 0.2 degrees
      C. Biting persistence, as measured by the number of bites and the time spent
      biting, also increases with increasing RH accompanied by a 13.1 degrees C
      increase in air temperature. Neurones in wall-pore sensilla on the palps respond
      to shifts in RH. CONCLUSIONS: Our results show that temperature acts
      synergistically with humidity to increase the rapidity and frequency of the
      biting response in tsetse above the levels induced by increasing temperature or
      humidity separately. Palp sensilla housing hygroreceptor cells, described here
      for the first time in tsetse, are involved in the perception of differences in
      RH.

PMID- 23958225
TI  - New normative values for handgrip strength: results from the UK Biobank.
AB  - OBJECTIVES: To develop normative values for right and left handgrip strength
      after stratification for confounders like gender, age, and height. DESIGN: Cross
      sectional, descriptive. SETTING: General population. PARTICIPANTS: A total of
      502,713 people living in the United Kingdom. INTERVENTION: None. MEASUREMENTS:
      Handgrip strength was measured using a Jamar hydraulic hand dynamometer, which is
      considered to be an accurate instrument to measure handgrip strength. In
      addition, self-reported chronic conditions and ethnic background were registered,
      and lung function was assessed using spirometry. RESULTS: After exclusion of all
      individuals with missing data, a nonwhite ethnic background, the presence of 1 or
      more self-reported conditions, and/or an obstructive lung function (defined as
      FEV1/FVC <0.7), new normative values for right and left handgrip strength were
      derived from 224,830 and 224,852 individuals (54.2% women; age: 55.0 [8.0] years;
      height: 169.0 [9.2] cm; body mass index: 26.9 [4.4] kg/m(2)) with a nonobstructed
      spirometry (FEV1: 3.0 [0.8] L). Men were stronger than women. Moreover,
      significant associations were found between handgrip strength and height, and
      between handgrip strength and age. Finally, percentiles 5, 10, 25, 50, 75, 90,
      and 95 were calculated for right and left handgrip strength, after stratification
      for gender, age, and height. CONCLUSION: The UK Biobank dataset provided the
      opportunity to determine new normative values for handgrip strength in men and
      women aged 39 to 73 years. These normative values take into consideration age,
      height, and measurement side. Therefore, these new normative handgrip strength
      values are of broad clinical interest.

PMID- 23958228
TI  - An agent-based model driven by tropical rainfall to understand the spatio
      temporal heterogeneity of a chikungunya outbreak.
AB  - Vector-borne diseases, such as dengue, malaria and chikungunya, are increasing
      across their traditional ranges and continuing to infiltrate new, previously
      unaffected, regions. The spatio-temporal evolution of these diseases is
      determined by the interaction of the host and vector, which is strongly dependent
      on social structures and mobility patterns. We develop an agent-based model
      (ABM), in which each individual is explicitly represented and vector populations
      are linked to precipitation estimates in a tropical setting. The model is
      implemented on both scale-free and regular networks. The spatio-temporal
      transmission of chikungunya is analysed and the presence of asymptomatic silent
      spreaders within the population is investigated in the context of implementing
      travel restrictions during an outbreak. Preventing the movement of symptomatic
      individuals is found to be an insufficient mechanism to halt the spread of the
      disease, which can be readily carried to neighbouring nodes via sub-clinical
      individuals. Furthermore, the impact of topology structure vs. precipitation
      levels is assessed and precipitation is found to be the dominant factor driving
      spatio-temporal transmission. 

PMID- 23958227
TI  - Hyperoxemia and long-term outcome after traumatic brain injury.
AB  - INTRODUCTION: The relationship between hyperoxemia and outcome in patients with
      traumatic brain injury (TBI) is controversial. We sought to investigate the
      independent relationship between hyperoxemia and long-term mortality in patients
      with moderate-to-severe traumatic brain injury. METHODS: The Finnish Intensive
      Care Consortium database was screened for mechanically ventilated patients with a
      moderate-to-severe TBI. Patients were categorized, according to the highest
      measured alveolar-arterial O2 gradient or the lowest measured PaO2 value during
      the first 24 hours of ICU admission, to hypoxemia (<10.0 kPa), normoxemia (10.0
      to 13.3 kPa) and hyperoxemia (>13.3 kPa). We adjusted for markers of illness
      severity to evaluate the independent relationship between hyperoxemia and 6-month
      mortality. RESULTS: A total of 1,116 patients were included in the study, of
      which 16% (n = 174) were hypoxemic, 51% (n = 567) normoxemic and 33% (n = 375)
      hyperoxemic. The total 6-month mortality was 39% (n = 435). A significant
      association between hyperoxemia and a decreased risk of mortality was found in
      univariate analysis (P = 0.012). However, after adjusting for markers of illness
      severity in a multivariate logistic regression model hyperoxemia showed no
      independent relationship with 6-month mortality (hyperoxemia vs. normoxemia OR
      0.88, 95% CI 0. 63 to 1.22, P = 0.43; hyperoxemia vs. hypoxemia OR 0.97, 95% CI
      0.63 to 1.50, P = 0.90). CONCLUSION: Hyperoxemia in the first 24 hours of ICU
      admission after a moderate-to-severe TBI is not predictive of 6-month mortality.

PMID- 23958229
TI  - Emergency and wilderness medicine training for physician astronauts on
      exploration class missions.

PMID- 23958230
TI  - Wild honey intoxication in the remote Himalaya.

PMID- 23958231
TI  - [Facial edema].

PMID- 23958232
TI  - [A coloured glans penis].

PMID- 23958233
TI  - Outcome of total knee arthroplasty in hemophilic arthropathy.
AB  - The clinical histories of 45 consecutively performed TKAs in 32 patients with
      hereditary bleeding disorders were reviewed retrospectively. The mean follow up
      was 88.7 (range, 24-232) months. The cumulative probability of infection free
      survival was 87.8% after 180 months. When removal of component was defined as
      endpoint, the survival probability was 86.4% after 180 months. In regression
      analysis no significant independent risk factors for infection or aseptic
      loosening were identified. The HSS score improved significantly from 45 to 85
      points. Hemophilic patients can be considered to be at high risk for prosthetic
      failure, our study has demonstrated favorable functional results of total knee
      arthroplasty in hemophilic patients.

PMID- 23958234
TI  - Research synthesis of recommended acetabular cup orientations for total hip
      arthroplasty.
AB  - Total hip arthroplasty (THA) is regarded as one of the most successful surgical
      procedures of modern times yet continues to be associated with a small but
      significant complication rate. Many early failures may be associated with poor
      component positioning with, in particular, acetabular component orientation
      dependent on the subjective judgement of the surgeon. In this paper, we compare
      the manufacturers' instructions on acetabular cup orientation with the literature
      based recommended safety zones and surgical technique, by transforming them onto
      a single, clinically-relevant framework in which the different reference systems,
      safety guidelines and current instrumentation surgical techniques can be
      evaluated. The observed limited consensus between results reflects ongoing
      uncertainty regarding the optimum acetabular component positioning. As
      malpositioning of the acetabular cup increases the risk of revision surgery, any
      ambiguity over the correct position can have a causal effect. Our analysis
      highlights the need for a surgical reference system which can be used to describe
      the position of the acetabular cup intra-operatively. 

PMID- 23958235
TI  - The results of total hip arthroplasty for fractured neck of femur in
      octogenarians.
AB  - The role of total hip arthroplasty (THA) for fracture in octogenarians remains
      unclear. Over a two-year period, 354 patients aged > 80 years were admitted with
      a displaced intracapsular hip fracture. Using defined clinical guidelines, 38
      patients underwent THA with a median age of 84 years, mean follow-up of 20
      months. Primary outcomes were dislocation, 30-day and one-year mortality,
      revision surgery and periprosthetic fracture. There were no dislocations or
      periprosthetic fractures and patient survival was 97% at 30 days and 87% at one
      year. There was one revision for deep infection. This study demonstrates that THA
      for selected octogenarians can be performed safely, allows the majority of
      patients to return to independent living and has a low complication rate.

PMID- 23958236
TI  - Understanding readmission after primary total hip and knee arthroplasty: who's at
      risk?
AB  - Readmission has been cited as an important quality measure in the Patient
      Protection and Affordable Care Act. We queried an electronic database for all
      patients who underwent Total Hip Arthroplasty or Total Knee Arthroplasty at our
      institution from 2006 to 2010 and identified those readmitted within 90 days of
      surgery, reviewed their demographic and clinical data, and performed a
      multivariable logistic regression analysis to determine significant risk factors.
      The overall 90-day readmission rate was 7.8%. The most common readmission
      diagnoses were related to infection and procedure-related complications. An
      increased likelihood of readmission was found with coronary artery disease,
      diabetes, increased LOS, underweight status, obese status, age (over 80 or under
      50), and Medicare. Procedure-related complications and wound complications
      accounted for more readmissions than any single medical complication.

PMID- 23958237
TI  - Intraoperative medial pivot affects deep knee flexion angle and patient-reported
      outcomes after total knee arthroplasty.
AB  - The aim of this study was to evaluate the relationship between clinical results
      including patient-reported outcomes and intraoperative knee kinematic patterns
      after total knee arthroplasty (TKA). A cross-sectional survey of forty
      consecutive medial osteoarthritis patients who had a primary TKA using a CT-based
      navigation system was conducted. Subjects were divided into two groups based on
      intraoperative kinematic patterns: a medial pivot group (n = 20) and a non-medial
      pivot group (n = 20). Subjective outcomes with the new Knee Society Score and
      clinical outcomes were evaluated. The functional activities, patient satisfaction
      and the knee flexion angle of the medial pivot group were significantly better
      than those of the non-medial pivot group. An intraoperative medial pivot pattern
      positively influences deep knee flexion and patient-reported outcomes.

PMID- 23958238
TI  - Interpretation of HLA single antigen bead assays.
AB  - The introduction of single antigen bead (SAB) assays for detection and
      quantitation of HLA antibodies has improved our ability to identify and manage
      allosensitized transplant candidates and recipients and to improve organ
      allocation, and was critical to the creation of national paired kidney exchanges.
      The principal limitations of the technology have been detailed in the literature
      and include artifacts resulting in non-specific background, variability, lack of
      standardization, and interpretive challenges. Accurate interpretation of SAB
      assays requires consideration of a number of factors, including identification of
      epitope reactivity patterns, mean fluorescence intensity (MFI) values, patient
      history, and appreciation of individual bead and assay nuances. The MFI value
      provides an estimate of relative HLA antibody levels although limited by
      saturation and epitope distribution effects. A better understanding of SAB assays
      and MFI values will be necessary to ensure appropriate application of these
      assays clinically and a higher quality of antibody data used in support of
      published clinical studies. 

PMID- 23958239
TI  - Introduction to a special issue in honour of W. Owen Saxton, David J. Smith and
      Dirk Van Dyck on the occasion of their 65th birthdays.

PMID- 23958240
TI  - Challenges to the implementation of International Health Regulations (2005) on
      preventing infectious diseases: experience from Julius Nyerere International
      Airport, Tanzania.
AB  - BACKGROUND: The International Health Regulations (IHR) (2005) is a legal
      instrument binding all World Health Organization (WHO) member States. It aims to
      prevent and control public health emergencies of international concern. Country
      points of entry (POEs) have been identified as potential areas for effective
      interventions to prevent the transmission of infectious diseases across borders.
      The agreement postulates that member states will strengthen core capacities
      detailed in the IHR (2005), including those specified for the POE. This study
      intended to assess the challenges faced in implementing the IHR (2005)
      requirements at Julius Nyerere International Airport (JNIA), Dar es Salaam.
      DESIGN: A cross-sectional, descriptive study, employing qualitative methods, was
      conducted at the Ministry of Health and Social Welfare (MoHSW), WHO, and JNIA. In
      depth interviews, focus group discussions (FGDs) and documentary reviews were
      used to obtain relevant information. Respondents were purposively enrolled into
      the study. Thematic analysis was used to generate study findings. RESULTS:
      Several challenges that hamper implementation of the IHR (2005) were identified:
      (1) none of the 42 Tanzanian POEs have been specifically designated to implement
      IHR (2005). (2) Implementation of the IHR (2005) at the POE was complicated as it
      falls under various uncoordinated government departments. Although there were
      clear communication channels at JNIA that enhanced reliable risk communication,
      the airport lacked isolated rooms specific for emergence preparedness and
      response to public health events. CONCLUSIONS: JNIA is yet to develop adequate
      core capacities required for implementation of the IHR (2005). There is a need
      for policy managers to designate JNIA to implement IHR (2005) and ensure that
      public health policies, legislations, guidelines, and practice at POE are
      harmonized to improve international travel and trade. Policy makers and
      implementers should also ensure that implementation of the IHR (2005) follow the
      policy implementation framework, particularly the contextual interaction theory
      which calls for the availability of adequate resources (inputs) and well
      organized process for the successful implementation of the policy.

PMID- 23958241
TI  - Inflammatory cytokines and chemokines, skeletal muscle and polycystic ovary
      syndrome: effects of pioglitazone and metformin treatment.
AB  - OBJECTIVE: Chronic low-grade inflammation is a common feature of insulin
      resistant states, including obesity and type 2 diabetes. Less is known about
      inflammation in Polycystic Ovary Syndrome (PCOS). Thus we evaluated the impact of
      PCOS on circulating cytokine levels and the effects of anti-diabetic therapies on
      insulin action, cytokine and chemokine levels and inflammatory signaling in
      skeletal muscle. METHODS: Twenty subjects with PCOS and 12 healthy normal cycling
      (NC) subjects of similar body mass index were studied. PCOS subjects received
      oral placebo or pioglitazone, 45 mg/d, for 6 months. All PCOS subjects then had
      metformin, 2 g/day, added to their treatment. Circulating levels of cytokines,
      chemokines, and adiponectin, skeletal muscle markers of inflammation and
      phosphorylation of signaling proteins, insulin action evaluated by the
      hyperinsulinemic/euglycemic clamp procedure and Homeostasis Model Assessment of
      Insulin Resistance were measured. RESULTS: Circulating levels of a number of
      cytokines and chemokines were generally similar between PCOS and NC subjects.
      Levels in PCOS subjects were not altered by pioglitazone or metformin treatment,
      even though whole body insulin action and adiponectin levels increased with
      pioglitazone. In spite of the lack of change in levels of cytokines and
      chemokines, several markers of inflammation in skeletal muscle were improved with
      Pio treatment. CONCLUSIONS: PCOS may represent a state of elevated sensitivity of
      inflammatory cells in skeletal muscle to cytokines and chemokines, a property
      that could be reversed by pioglitazone treatment together with improved insulin
      action.

PMID- 23958242
TI  - Potential effect of physiotherapeutic treatment on mortality rate in patients
      with severe sepsis and septic shock: a retrospective cohort analysis.
AB  - PURPOSE: The aim of the study was to examine the onset and frequency of
      physiotherapeutic interventions (PTI) and their potential effects on the
      intensive care unit (ICU) mortality rate in patients with severe sepsis or septic
      shock. MATERIAL AND METHODS: Retrospective data analysis. Univariate and
      multivariate Cox proportional-hazards regression analyses were performed.
      RESULTS: About 6.2% of all patients (n = 999, length of ICU stay 12 days,
      averaged SOFA score 14) developed sepsis within three years. Of these, 77%
      received at least once PTI. The relative number of PTI (RNPTI index, individually
      calculated by the number of PTI/length of stay) in patients with sepsis was 42%.
      The first physiotherapeutic treatment was five days after ICU admission. Cox
      regression multivariate analysis adjusted by disease severity scores, sedation
      state and other clinical variables found RNPTI index as significant risk factor
      for the ICU mortality rate (hazard ratio, 0.982; 95% confidence interval, 0.974
      0.990; P < .001). CONCLUSIONS: Physiotherapists routinely assess and treat
      patients with sepsis. The frequency of PTI was associated with an improved
      outcome. Prospective studies are necessary to confirm the potential favorable
      impact.

PMID- 23958243
TI  - Initial fractal exponent of heart rate variability is associated with success of
      early resuscitation in patients with severe sepsis or septic shock: a prospective
      cohort study.
AB  - INTRODUCTION: Heart rate variability (HRV) reflects autonomic nervous system tone
      as well as the overall health of the baroreflex system. We hypothesized that loss
      of complexity in HRV upon intensive care unit (ICU) admission would be associated
      with unsuccessful early resuscitation of sepsis. METHODS: We prospectively
      enrolled patients admitted to ICUs with severe sepsis or septic shock from 2009
      to 2011. We studied 30 minutes of electrocardiogram, sampled at 500 Hz, at ICU
      admission and calculated heart rate complexity via detrended fluctuation
      analysis. Primary outcome was vasopressor independence at 24 hours after ICU
      admission. Secondary outcome was 28-day mortality. RESULTS: We studied 48
      patients, of whom 60% were vasopressor independent at 24 hours. Five (10%) died
      within 28 days. The ratio of fractal alpha parameters was associated with both
      vasopressor independence and 28-day mortality (P = .04) after controlling for
      mean heart rate. In the optimal model, Sequential Organ Failure Assessment score
      and the long-term fractal alpha parameter were associated with vasopressor
      independence. CONCLUSIONS: Loss of complexity in HRV is associated with worse
      outcome early in severe sepsis and septic shock. Further work should evaluate
      whether complexity of HRV could guide treatment in sepsis.

PMID- 23958244
TI  - Persistent organic pollutants and hyperuricemia in the U.S. general population.
AB  - BACKGROUND: Background exposure to persistent organic pollutants (POPs) has
      emerged as a new risk factor for metabolic syndrome (MetS), while hyperuricemia
      is associated with MetS through unclear mechanisms. OBJECTIVE: We examined cross
      sectional data for consistency with the hypothesis that POPs are a common
      underlying risk factor of both MetS and hyperuricemia. METHODS: We evaluated
      associations of POPs with hyperuricemia in subjects aged >=20 years in the
      population-based National Health and Nutrition Examination Survey (NHANES) 2003
      2004. Sample size was n = 1331 for organochlorine (OC) pesticides and n = 1299
      for polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans
      (PCDFs), and polychlorinated biphenyls (PCBs). RESULTS: Among all subjects, the
      risk of hyperuricemia was higher for higher serum concentrations of OC
      pesticides, PCDDs, and dioxin-like PCBs. PCDFs and nondioxin-like PCBs did not
      show any clear trend. Adjusted odds ratios (ORs) for OC pesticides, PCDDs, and
      dioxin-like PCBs were 1.0, 2.4, 2.3, 3.0, and 2.5 (P trend = 0.05), 1.0, 1.6,
      1.4, 2.1, and 2.5 (P trend = 0.01), and 1.0, 1.3, 1.4, 1.3, and 2.4 (P trend =
      0.04). When we restricted the analyses to subjects without MetS, all these
      associations appeared to strengthen. CONCLUSION: This study is consistent with
      our hypothesis that the risk of hyperuricemia relates to background exposure to a
      mixture of POPs even among persons without MetS. There should be further research
      about whether avoiding exposure to POPs and otherwise decreasing body burden of
      POPs would be helpful to prevent or manage hyperuricemia or gout.

PMID- 23958245
TI  - The positive relationship of serum paraoxonase-1 activity with apolipoprotein E
      is abrogated in metabolic syndrome.
AB  - BACKGROUND: High density lipoproteins (HDL) contain paraoxonase-1 (PON-1), which
      has strong anti-oxidative properties. Apolipoprotein E (apoE) may enhance PON-1
      activity in vitro, but the extent to which PON-1 activity is determined by
      circulating apoE levels is unknown. Here we determined relationships of serum PON
      1 activity with apoE in subjects without and with metabolic syndrome (MetS).
      METHODS: We measured PON-1 activity (arylesterase activity), plasma apoE and
      serum amyloid A (SAA) in 93 subjects without and in 75 subjects with MetS (25 and
      54 subjects with Type 2 diabetes mellitus (T2DM), respectively; p < 0.001).
      RESULTS: PON-1 activity was lower in MetS (p < 0.005) coinciding lower HDL
      cholesterol, apoA-I (p < 0.001)) and SAA levels (p < 0.01), whereas apoE was
      increased in relation to higher triglycerides (p < 0.01). In subjects without
      MetS, PON-1 activity was correlated positively with apoE (r = 0.376, p < 0.001),
      but this relationship was absent in MetS subjects (r = 0.085, p = 0.47). Multiple
      linear regression analysis showed that the relationship of PON-1 activity with
      apoE was different in subjects with MetS compared to subjects without MetS (beta
      = -0.270, p = 0.014 for the interaction between apoE and MetS), independently
      from age, sex, T2DM, use of glucose lowering drugs, anti-hypertensives and the
      inverse relation with SAA levels (p = 0.008). Of the individual MetS components,
      apoE only interacted with low HDL-C on PON-1 activity (beta = -0.175, p = 0.074).
      The relationship of apoE with PON-1 activity was neither modified by T2DM (p =
      0.49), nor by SAA (p = 0.79). CONCLUSION: Higher apoE levels may confer higher
      PON-1 activity. The relationship of PON-I activity with total plasma apoE is
      apparently abrogated in MetS.

PMID- 23958246
TI  - Gender-related differences in outcome after BMS or DES implantation in patients
      with ST-segment elevation myocardial infarction treated by primary angioplasty:
      insights from the DESERT cooperation.
AB  - BACKGROUND: Several studies have found that among patients with ST-segment
      elevation myocardial infarction (STEMI) treated by thrombolysis, female sex is
      associated with a worse outcome. However, still controversial is the prognostic
      impact of gender in primary angioplasty, especially in the era of drug-eluting
      stents (DES). Therefore, the aim of this study was to investigate sex-related
      differences in clinical outcome in patients with STEMI treated with primary
      angioplasty with Bare-Metal Stent (BMS) or DES. METHODS: Our population is
      represented by 6298 STEMI patients undergoing primary angioplasty and stent
      implantation included in the DESERT database. Follow-up data were collected from
      3 to 6 years after primary angioplasty. RESULTS: Female gender was observed in
      1466 (23.2%) out of 6298 STEMI patients. Women were older (65.3 +/- 12.4 vs 59.3
      +/- 11.4 years, p < 0.001), with higher prevalence of diabetes (18.6% vs 14.5%, p
      < 0.001), hypertension (52.4% vs 41.4%, p < 0.001), slightly longer ischemia time
      (272 +/- 247 vs 258 +/- 220 min, p = 0.06). No difference was observed in terms
      of angiographic and procedural characteristics. Follow-up data were available at
      a mean of 1201 +/- 441 days. At long-term follow-up female gender was associated
      with a significantly higher rate of death (11.7% vs 8.5%, HR [95% CI] = 1.45
      [1.18-1.78], p < 0.001), while no difference was observed in terms of
      reinfarction (HR [95% CI] = 1.14 [0.89-1.45], p = 0.3), ST (HR [95% CI] = 1.12
      [0.85-1.48], p = 0.4), with similar temporal distribution (acute, subacute, late
      and very late) between male and female patients, and no difference in TVR (HR
      [95% CI] = 1.11 [0.95-1.3], p = 0.2, p = 0.2). These results were confirmed in
      both patients receiving BMS or DES. The impact of female gender on mortality
      disappeared after correction for baseline confounding factors (HR [95% CI] = 0.88
      [0.71-1.09], p = 0.25). CONCLUSIONS: This study shows that in patients with STEMI
      treated by primary angioplasty, female gender is associated with higher mortality
      rate in comparison with men, and this is mainly due to their higher clinical and
      angiographic risk profiles. In fact, female sex did not emerge as an independent
      predictor of mortality.

PMID- 23958247
TI  - Non-compressible arterial disease and the risk of coronary calcification in type
      2 diabetes.
AB  - OBJECTIVE: Ankle-brachial index (ABI) screening is recommended for the detection
      of asymptomatic peripheral arterial disease (PAD) in at-risk populations,
      including diabetics. A low ABI identifies obstructive lower extremity vascular
      disease and predicts CVD events and increased mortality. A high ABI represents
      non-compressible arterial disease (NCAD), and is also associated with increased
      mortality and vascular events. Our objective is to investigate whether low and
      high ABI have distinct patterns of association with cardiovascular disease (CVD)
      risk factors and subclinical atherosclerosis in individuals with type-II diabetes
      mellitus. METHODS: The Penn Diabetes Heart Study (PDHS) is a prospective
      observational cohort of diabetic individuals without clinically evident CVD.
      Multivariate logistic and Tobit linear regression were used to compare CVD risk
      factors and coronary artery (CAC) among 1863 subjects with PAD (ABI <= 0.9), NCAD
      (ABI >= 1.4 or non-compressible) or normal ABI (0.91-1.39). RESULTS: Compared to
      those with normal ABI, PAD was associated with smoking, obesity, and lower HDL-c;
      while diabetes duration and reduced renal function were associated with NCAD.
      Both PAD and NCAD were independently associated with increased CAC compared to
      those with normal ABI, and these relationships were not attenuated in multiply
      adjusted models. CONCLUSION: NCAD bears a distinct relationship to traditional
      CVD risk factors among diabetics, though like PAD is independently associated
      with increased CAC. These findings support the recognition of NCAD as a high-risk
      phenotype and provide additional relevance to ABI screening in diabetics.

PMID- 23958248
TI  - Modulation of NO and ROS production by AdiNOS transduced vascular cells through
      supplementation with L-Arg and BH4: implications for gene therapy of restenosis.
AB  - OBJECTIVE: Gene therapy with viral vectors encoding for NOS enzymes has been
      recognized as a potential therapeutic approach for the prevention of restenosis.
      Optimal activity of iNOS is dependent on the intracellular availability of L-Arg
      and BH4 via prevention of NOS decoupling and subsequent ROS formation. Herein, we
      investigated the effects of separate and combined L-Arg and BH4 supplementation
      on the production of NO and ROS in cultured rat arterial smooth muscle and
      endothelial cells transduced with AdiNOS, and their impact on the antirestenotic
      effectiveness of AdiNOS delivery to balloon-injured rat carotid arteries. METHODS
      AND RESULTS: Supplementation of AdiNOS transduced endothelial and vascular smooth
      muscle cells with L-Arg (3.0 mM), BH4 (10 MUM) and especially their combination
      resulted in a significant increase in NO production as measured by nitrite
      formation in media. Formation of ROS was dose-dependently increased following
      transduction with increasing MOIs of AdiNOS. Exposure of RASMC to AdiNOS tethered
      to meshes via a hydrolyzable cross-linker, modeling viral delivery from stents,
      resulted in increased ROS production, which was decreased by supplementation with
      BH4 but not L-Arg or L-Arg/BH4. Enhanced cell death, caused by AdiNOS
      transduction, was also preventable with BH4 supplementation. In the rat carotid
      model of balloon injury, intraluminal delivery of AdiNOS in BH4-, L-Arg-, and
      especially in BH4 and L-Arg supplemented animals was found to significantly
      enhance the antirestenotic effects of AdiNOS-mediated gene therapy. CONCLUSIONS:
      Fine-tuning of iNOS function by L-Arg and BH4 supplementation in the transduced
      vasculature augments the therapeutic potential of gene therapy with iNOS for the
      prevention of restenosis.

PMID- 23958249
TI  - Specific somatostatin receptor II expression in arterial plaque: (68)Ga-DOTATATE
      autoradiographic, immunohistochemical and flow cytometric studies in apoE
      deficient mice.
AB  - BACKGROUND: The rupture of atherosclerotic plaques is triggered by inflammation.
      Specific detection of inflammation is therefore the focus of many investigations.
      Noninvasive imaging methods, such as positron emission tomography (PET), also are
      suited for this purpose. (68)Ga-DOTATATE is a (68)Ga-labeled radiotracer with
      specific affinity to somatostatin receptor subtype-2 (SSTR-2). SSTR-2 was found
      specifically expressed on human macrophages/monocytes. OBJECTIVE: We aimed to
      confirm the distribution of SSTR-2 in inflammatory plaques, and to assess its co
      localization with macrophages within the plaques. We also assessed (68)Ga
      DOTATATE uptakes in plaques by autoradiography. METHOD: Apolipoprotein E (ApoE)-/
      mice on a high-cholesterol diet were injected with (68)Ga-DOTATATE. The animals
      were sacrificed and aorta sections were examined using autoradiography and
      immunohistochemistry. Furthermore, expression of SSTR-2 was analyzed by flow
      cytometry. Western blot was conducted to assess SSTR-2 regulation in basal and
      lipopolysaccharide (LPS)-activated state. To evaluate the specificity of the
      (68)Ga-DOTATATE, the sections were pre-incubated with monoclonal SSTR-2 antibody
      before autoradiography. RESULT: Autoradiographic imaging showed uptake of (68)Ga
      DOTATATE co-localized with the macrophage-rich plaques by immunohistochemical
      examination. A high expression of SSTR-2 on macrophages was found by flow
      cytometry and western blot. Stimulation with lipopolysaccharide did not alter
      expression of SSTR-2 in macrophages. CONCLUSION: Due to its specific binding to
      macrophages, (68)Ga-DOTATATE might be a suitable radiotracer for the evaluation
      of inflammatory activity in unstable plaques.

PMID- 23958250
TI  - Ionizing radiation and atherosclerosis: current knowledge and future challenges.
AB  - The evaluation of the health effects of low-dose ionizing radiation has always
      been a focus of debate and investigation within the scientific community. During
      the last decade, epidemiological studies provided evidence that an excess risk of
      cardiovascular diseases (CVDs) can be associated with moderate and low dose
      radiation. The precise quantification of CVD risk in the low-dose radiation range
      (<500 mSv) is not well characterized, and it is unclear whether there is a
      threshold dose below which there is no risk. A limited number of studies with
      imaging surrogate endpoints and cardiovascular biomarkers in asymptomatic
      patients revealed early signs of cardiovascular alterations, even at a low dose.
      In vitro studies have shown that several mechanisms, including endothelial
      dysfunction, inflammation, oxidative stress, alterations of coagulation and
      platelet activity may have a relevant role in radiation-induced cardiovascular
      effects. Exposure to high-dose data in experimental models accelerates the
      development of atherosclerosis, predisposing to the formation of an inflammatory,
      thrombotic plaque phenotype, especially in animals that are genetically
      predisposed to this disease. On the contrary, low dose exposure produced both
      protective and detrimental effects, suggesting that multiple mechanisms may
      influence radiation-induced atherosclerosis. However, only very limited and
      specific information can be obtained from cell cultures and animal models.
      Planned studies of radiation-exposed cohorts need to be conducted to explore
      biological mechanisms of low-dose radiation-associated cardiovascular disease.
      Further investigations with functional imaging to assess vascular function and
      cardiovascular biomarkers have great potential for providing new insights into
      low-dose radiation cardiovascular risk, especially in occupational exposure and
      modern medicine.

PMID- 23958251
TI  - Ezetimibe decreases serum oxidized cholesterol without impairing bile acid
      synthesis in Japanese hypercholesterolemic patients.
AB  - OBJECTIVE: Cholesterol and diet-derived oxidized cholesterol are absorbed in the
      small intestine and eliminated by bile acids. We determined whether ezetimibe, a
      selective cholesterol absorption inhibitor, changes serum oxidized cholesterol
      levels. METHODS: We measured levels of plant sterols, cholesterol precursors, and
      oxysterols by gas chromatography-mass spectrometry in 47 hypercholesterolemics
      and 32 controls. Twenty-four hypercholesterolemics received 10 mg ezetimibe/day
      for 4 weeks. RESULTS: Plant sterols were 30-42% higher in hypercholesterolemics
      than in controls and positively correlated with low-density lipoprotein
      cholesterol (LDL-C). Ezetimibe decreased plant sterols by 21-53%, but did not
      change bile acid synthesis markers. 7beta-hydroxycholesterol, a marker for non
      enzymatic oxidation of cholesterol, was 66% higher in hypercholesterolemics than
      controls. Ezetimibe decreased 7beta-hydroxycholesterol levels by 15% regardless
      of LDL-C reduction. CONCLUSIONS: Ezetimibe decreases serum oxidized cholesterol
      generated by non-enzymatic reactions without impairing bile acid synthesis.
      Ezetimibe may maintain cholesterol excretion into bile and alleviate the diet
      derived oxidative burden.

PMID- 23958252
TI  - Efficacy and safety of the cholesteryl ester transfer protein inhibitor
      anacetrapib in Japanese patients with dyslipidemia.
AB  - OBJECTIVE: This study evaluated the effects of anacetrapib (ANA) on lipids and
      safety when administered as monotherapy or in combination with atorvastatin (ATV)
      in Japanese patients with dyslipidemia. METHODS: Patients (n = 407) were
      randomized equally to 1 of 10 groups: placebo, ATV 10 mg, ANA 10, 40, 100, or 300
      mg once daily, and the same ANA doses in combination with ATV 10 mg. Patients
      were treated with study medication for 8 weeks and followed for an additional 8
      weeks, during which ANA was switched to placebo. RESULTS: For the placebo and ANA
      monotherapy groups (10, 40, 100, and 300 mg), least squares mean percent changes
      from baseline at Week 8 for low-density lipoprotein cholesterol (LDL-C)
      calculated by the Friedewald equation were 3%, -12%, -27%, -32%, and -32%,
      respectively, and for high-density lipoprotein-cholesterol (HDL-C) were 1%, 56%,
      116%, 134%, and 159%, respectively (p < 0.001 vs. placebo for all doses). All ANA
      doses co-administered with ATV 10 mg produced significantly greater LDL-C
      reductions and HDL-C increases compared with ATV 10 mg monotherapy. ANA was well
      tolerated, and dose-dependent relationships for adverse events were not observed
      across treatment groups. Changes from baseline in blood pressure and electrolytes
      were not significantly different between the active and control treatment groups.
      CONCLUSION: ANA, as monotherapy or co-administered with ATV, produced significant
      reductions in LDL-C and increases in HDL-C. ANA was generally well tolerated in
      Japanese patients with dyslipidemia.

PMID- 23958253
TI  - Relationship of dyspnea vs. typical angina to coronary artery disease severity,
      burden, composition and location on coronary CT angiography.
AB  - OBJECTIVE: Symptom presentations suspicious for coronary artery disease (CAD)
      vary widely. While dyspnea is associated with worse prognosis than typical angina
      (TypAng) for patients referred for non-invasive CAD imaging, the relation of
      dyspnea vs. TypAng to adverse measures of CAD prognosis-including severity,
      burden, composition, and myocardium at risk-has not been examined. METHODS: We
      studied 1443 consecutive individuals without known CAD (mean 61 +/- 13 years,
      61.6% men) undergoing coronary computed tomographic angiography (CCTA) who
      presented with dyspnea (n = 170), TypAng (n = 249) or no dyspnea or TypAng (n =
      1024). Multivariable logistic regression was performed to evaluate the
      association of dyspnea or TypAng to obstructive CAD (>=70% stenosis), plaque
      burden (total segments with plaque), composition (noncalcified, partially
      calcified) and location (proximal, mid, or distal location in a coronary artery).
      RESULTS: By multivariable logistic regression, both dyspnea (OR1.9, 95% CI 1.1
      3.3, p = 0.02) and TypAng (OR1.9, 95% CI 1.2-3.1, p = 0.01) were associated with
      obstructive CAD as compared to individuals without dyspnea or TypAng, while
      dyspnea (OR1.8, 95% CI 1.1-3.1, p = 0.02), but not TypAng (OR1.1, 95% CI 0.7-1.6,
      p = 0.76) was associated with plaque in the proximal portions of coronary
      arteries. Neither symptom type was associated with differences in plaque burden
      nor composition. CONCLUSION: Both dyspnea and TypAng are associated with higher
      rates of obstructive CAD compared to those without dyspnea or TypAng, but only
      dyspnea is associated with coronary plaque in proximal vessel portions.

PMID- 23958255
TI  - Cystatin C - More than a filtration marker?

PMID- 23958254
TI  - The combination of Helicobacter pylori- and cytotoxin-associated gene-A
      seropositivity in relation to the risk of myocardial infarction in middle-aged
      Japanese: The Japan Public Health Center-based study.
AB  - BACKGROUND: Limited evidence is available concerning the impact of the
      combination of Helicobacter pylori- (H. pylori) and cytotoxin-associated gene-A
      (CagA)-positivity on the risk of myocardial infarction (MI) and stroke,
      particularly in Asian populations, in which the prevalence of H. pylori infection
      is high. METHODS: A prospective, nested case-control study was conducted to
      examine the association between H. pylori and CagA and risk of MI and stroke
      within a cohort of 29,876 men and women aged 40-69 years with no history of heart
      disease, stroke or cancer. Participants completed a risk factor survey and
      donated blood samples between 1990 and 1994. Systematic cardiovascular
      surveillance was performed through 2002. One control for each stroke case and two
      controls for each MI case were matched by sex, age, date of blood sampling, time
      since last meal and study location. RESULTS: During the follow-up period, there
      were 600 strokes and 106 MIs. H. pylori-IgG positivity was not associated with
      the risk of MI, while CagA positivity tended to be associated with it (OR = 1.72,
      95%CI: 0.91-3.26, p = 0.10). We found no association between H. pylori or CagA
      and risk of stroke. CONCLUSIONS: H. pylori infection was not significantly
      associated with risk of MI and stroke among middle-aged Japanese. However, CagA
      positivity tended to be associated with MI.

PMID- 23958257
TI  - Benefits of potassium intake on metabolic syndrome: The fourth Korean National
      Health and Nutrition Examination Survey (KNHANES IV).
AB  - OBJECTIVE: Potassium intake may be associated with metabolic syndrome and its
      components, but there has been little evidence so far. We evaluated the
      association between the metabolic syndrome and potassium intake in the general
      population. METHODS: Participants were 7542 adults (>=20 years of age) from the
      fourth Korean National Health and Nutrition Examination Survey (2007-2009), which
      is a cross-sectional survey of a nationally representative sample of the Korean
      population. Data were obtained from standardized questionnaires as well as
      physical and laboratory examination reports. The 24-h recall method was used for
      dietary assessment. Metabolic syndrome was defined based on the modified National
      Cholesterol Education Program-Adult Treatment Panel III criteria. Multivariable
      logistic regression was performed to estimate the odds of metabolic syndrome and
      its components across potassium intake quartiles. RESULTS: After adjusting for
      various lifestyle and dietary confounders, subjects in the highest quartile of
      potassium intake had 39% lower odds for metabolic syndrome compared to those in
      the lowest quartile (adjusted odds ratio [aOR] = 0.61; 95% confidence interval
      [CI]: 0.42-0.89; p for trend: 0.013). This association was consistent for both
      sexes. Among the components of metabolic syndrome, potassium intake was inversely
      related to abdominal obesity and fasting hyperglycemia in multivariate analysis
      (p for trend = 0.049 and 0.010, respectively). CONCLUSION: Our results reveal a
      significant inverse association between potassium intake and metabolic syndrome
      in adults. Further studies are required to confirm this association.

PMID- 23958256
TI  - Absolute coronary artery calcium score is the best predictor of non-calcified
      plaque involvement in patients with low calcium scores (1-100).
AB  - OBJECTIVE: We sought to identify the predictors of non-calcified plaque (NCP)
      burden in patients with low coronary artery calcium (CAC) scores of 1-100.
      METHODS: We studied 920 consecutive patients clinically referred for coronary CT
      angiography (CCTA) with concomitant CAC scoring. The 276 patients with CAC 1-100
      were divided into four groups based on the CAC score: CAC = 0, 1-10, 11-50, and
      51-100. Univariate and multivariate linear regression analyses were performed for
      the demographic, risk factor, and CAC score predictors of number of coronary
      segments with NCP. RESULTS: Mean age was 55 +/- 11 years and 56% were women.
      Demographics and risk factors failed to identify NCP involvement in univariate
      models. The lone predictor of NCP burden was the absolute CAC score, which was
      persistently associated with NCP in multivariable models (CAC 51-100 vs. CAC 1
      10, beta-coefficient 0.35, p = 0.03). CONCLUSIONS: Absolute CAC score is the lone
      robust predictor of NCP burden when CAC is 1-100. Risk within this mild coronary
      calcification group is likely heterogeneous, driven by the absolute CAC score.

PMID- 23958258
TI  - Ankle-brachial index in relation to the natriuretic peptide system polymorphisms
      and urinary sodium excretion in Chinese.
AB  - OBJECTIVE: Recent studies have demonstrated that the natriuretic pepetides induce
      endothelial regeneration and angiogenesis after vascular injury through the
      autocrine or paracrine action, and might have an inhibitory effect on
      atherosclerosis. We therefore systematically investigated single nucleotide
      polymorphisms (SNPs) in the natriuretic peptide system in relation to ankle
      brachial index (ABI) in a Chinese population. METHODS: The study population was
      recruited from a mountainous area 500 km south of Shanghai from 2003 to 2009.
      Using the SNapShot method, we first genotyped 951 subjects enrolled in 2005 for
      16 SNPs and then the remaining 1355 subjects as validation for 5 SNPs selected
      from the primary study. ABI and plasma proBNP were measured using the Omron VP
      2000/1000 device and the Elecsys proBNP immunoassay, respectively. RESULTS:
      Overall, the genetic associations were not significant (P >= 0.07). However, in
      the primary study, there was significant (Pint <= 0.045) interaction between 3
      SNPs (rs6668352, rs198388, and rs198389) at the NPPA-NPPB locus and urinary
      sodium excretion in relation to ABI, and the rs6668352 polymorphism had the
      strongest association (Pint = 0.018). In the primary combined with the validation
      study populations, the interaction between the rs6668352 polymorphism and urinary
      sodium excretion in relation to ABI remained statistically significant (Pint =
      0.0036). After adjustment for covariates, the rs6668352 A allele carriers,
      compared with GG homozygotes, had a higher ABI (mean +/- standard error, 1.103 +/
      0.006 vs. 1.084 +/- 0.004, P = 0.009) and lower risk of peripheral arterial
      disease (PAD, defined as an ABI < 0.90, odds ratio 0.37, 95% confidence interval:
      0.14-0.98, P = 0.04) in the subjects of high sodium intake. CONCLUSION: The minor
      alleles of 3 SNPs at the NPPA-NPPB locus are associated with a lower risk of PAD,
      especially in the subjects of high sodium intake.

PMID- 23958259
TI  - Decreased numbers of regulatory T cells are associated with human atherosclerotic
      lesion vulnerability and inversely correlate with infiltrated mature dendritic
      cells.
AB  - PURPOSE: Mature dendritic cells (DCs) play a crucial role in the inflammatory
      process within atherosclerotic lesions by stimulation of effector T cells, which
      can contribute to plaque instability. Interactions between DCs and regulatory T
      cells (Treg), which regulate immune response by attenuating acute inflammation,
      are postulated to be involved in the pathogenesis of autoimmune diseases. We
      investigated a possible correlation between infiltrated DCs and Treg in human
      atherosclerotic plaques. METHODS: Cross-sections of 40 human carotid
      endarterectomy specimens were classified into groups of stable and vulnerable
      plaques using Trichrome staining. Immunohistochemical staining of plaques was
      used to detect infiltrated total (S100) and mature DCs (fascin, DC-LAMP, CD83),
      Treg (CD3, Foxp3), and to analyze the inflammatory state of the plaques (CD3, COX
      2, CD68). In addition, RNA was isolated from plaque specimens and quantitative
      real-time PCR was performed to analyze transcription rates of DC markers (CD11c,
      CD209, HLA-DR), maturation markers (CD80, CD83, CD86), Treg-associated genes
      (CTLA-4, Foxp3) and of pro- and anti-inflammatory cytokines (TGFbeta-family, IL
      10, IFN-gamma, IL-17alpha, IL-6). Migration assays and adhesion experiments were
      performed, to investigate the effects of Treg on mature DCs in vitro. RESULTS: As
      compared with stable plaques, vulnerable lesions were characterized by increased
      numbers of COX-2-expressing cells and T lymphocytes, indicating an enhanced
      inflammatory process. In vulnerable plaques, numbers of total and mature DCs were
      significantly higher in the inflammatory plaque shoulder, whereas the numbers of
      Treg were decreased compared to stable plaques. This inverse correlation and the
      association of the observed infiltration rates with plaque stability, were
      confirmed by PCR analyses, showing increased transcription levels of DC-specific
      markers, decreased mRNA expression of Treg-associated genes and decreased anti
      inflammatory cytokines in vulnerable atherosclerotic plaques. In vitro, pre
      incubation of mature DCs with Treg resulted in decreased DC migration and
      inhibited the adhesion of DCs to endothelial cells under non-uniform shear
      stress. CONCLUSIONS: The results of our study provide novel insights in the
      direct interaction of mature DCs and Treg in plaque inflammation and stability.

PMID- 23958261
TI  - Lipoprotein remnants and dense LDL are associated with features of unstable
      carotid plaque: a flag for non-HDL-C.
AB  - OBJECTIVE: We investigated the association between cholesterol across the LDL
      density range and in the VLDL and IDL particles with the prevalence of
      inflammatory cells in plaques of patients with severe carotid artery stenosis.
      METHODS: Forty-five patients undergoing carotid endarterectomy were studied.
      Plaque specimens were analyzed for cellular composition by immunocytochemistry
      using monoclonal antibodies. Lipoprotein subclasses were separated by gradient
      ultracentrifugation. RESULTS: We found no correlations between LDL-C, HDL-C and
      plasma triglyceride levels with plaque cellular composition. On the other hand,
      macrophage content was significantly related to cholesterol in the dense LDL
      subclasses (r = 0.30, p < 0.01) and in the triglyceride-rich lipoprotein
      remnants, namely dense VLDL and IDL particles (r = 0.46, p < 0.01). HDL
      subclasses were not correlated with plaque cellular composition. In a mirror
      manner, smooth muscle cells were inversely associated with cholesterol levels of
      the dense LDL subclasses (r = -0.32, p < 0.01 fraction 10; r = -0.26, p < 0.05
      fraction 11) while only a non-significant trend was observed with the cholesterol
      in the VLDL-IDL fractions. These results provide the pathophysiological
      background to account for the relevance of non-HDL-C as the only lipid parameter,
      aside LDL density, significantly associated (beta = 0.351, p = 0.021) with
      carotid plaque macrophage content. CONCLUSIONS: We provide evidence that
      lipoprotein subclasses, specifically cholesterol in the dense LDL fractions and
      in the triglyceride-rich lipoprotein remnants, significantly affect carotid
      plaque cellular composition, in particular macrophages content.

PMID- 23958260
TI  - Plasma levels of cathepsins L, K, and V and risks of abdominal aortic aneurysms:
      a randomized population-based study.
AB  - BACKGROUND: Cathepsin L (CatL), cathepsin K (CatK), and cathepsin V (CatV) are
      potent elastases implicated in human arterial wall remodeling. Whether plasma
      levels of these cathepsins are altered in patients with abdominal aortic
      aneurysms (AAAs) remains unknown. METHODS AND RESULTS: Plasma samples were
      collected from 476 male AAA patients and 200 age-matched male controls to
      determine CatL, CatK, and CatV levels by ELISA. Student's t-test demonstrated
      significantly higher plasma CatL levels in AAA patients than in controls (P <
      0.0001), whereas CatK and CatV levels were lower in AAA patients than in controls
      (P = 0.052, P = 0.025). ROC curve analysis confirmed higher plasma CatL levels in
      AAA patients than in controls (P < 0.001). As potential confounders, current
      smoking and use of angiotensin-converting enzyme (ACE) inhibitors, aspirin,
      clopidogrel, and statins associated with significantly increased plasma CatL.
      Pearson's correlation test demonstrated that plasma CatL associated positively
      with CatS (r = 0.43, P < 0.0001), body-mass index (BMI) (r = 0.07, P = 0.047) and
      maximal aortic diameter (r = 0.29, P < 0.001), and negatively with lowest
      measured ankle-brachial index (ABI) (r = -0.22, P < 0.001). Plasma CatL remained
      associated positively with CatS (r = 0.43, P < 0.0001) and aortic diameter (r =
      0.212, P < 0.001) and negatively with ABI (r = -0.10, P = 0.011) after adjusting
      for the aforementioned potential confounders in a partial correlation analysis.
      Multivariate logistic regression analysis indicated that plasma CatL was a risk
      factor of AAA before (odds ratio [OR] = 3.04, P < 0.001) and after (OR = 2.42, P
      < 0.001) the same confounder adjustment. CONCLUSIONS: Correlation of plasma CatL
      levels with aortic diameter and the lowest ABI suggest that this cysteinyl
      protease plays a detrimental role in the pathogenesis of human peripheral
      arterial diseases and AAAs.

PMID- 23958262
TI  - Fibrate therapy and circulating adiponectin concentrations: a systematic review
      and meta-analysis of randomized placebo-controlled trials.
AB  - BACKGROUND: Several lines of evidence have indicated the insulin-sensitizing,
      anti-diabetic and anti-atherosclerotic properties of adiponectin, as well as the
      inverse association between circulating levels of this adipokine and development
      of cardiovascular outcomes. Improvement of adiponectin status has been reported
      as a pleiotropic effect of fibrate therapy, but the findings have not been
      conclusive. OBJECTIVE: To systematically review and meta-analyze available
      evidence from randomized placebo-controlled trials (RCTs) on the impact of
      fibrate therapy on circulating levels of adiponectin. METHODS: A comprehensive
      literature search in Medline was carried out to identify RCTs comparing the
      effect of fibrate therapy vs. placebo on circulating concentrations of
      adiponectin. A meta-analysis of eligible studies was performed using a random
      effects model. Quality assessment, sensitivity analysis and publication bias
      evaluations were conducted using standard methods. RESULTS: Twelve RCTs
      comprising 443 cases and 437 controls met the selection criteria for systematic
      review, out of which 9 RCTs (399 cases and 401 controls) were included in the
      meta-analysis. Quantitative data synthesis revealed a significant effect for
      fibrate therapy in increasing circulating adiponectin levels (weighed mean
      difference: 0.38 MUg/mL; 95% confidence interval: 0.13-0.63 MUg/mL; p = 0.003).
      The effect size remained statistically significant when restricting the analysis
      to fenofibrate trials [0.31 (0.21-0.42) MUg/mL; p < 0.00001). The observed effect
      was robust in sensitivity analyses and independent of fibrate dose. Imputation
      for potential missing studies led to the estimation of a greater effect size for
      fibrate therapy [0.53 (0.24-0.82) MUg/mL]. CONCLUSION: The present meta-analysis
      suggests that fibrate therapy increases circulating levels of adiponectin.
      Whether increase in adiponectin levels contributes to reduction of cardiovascular
      effects in subjects with dyslipidemia treated with fibrates merits further
      investigation.

PMID- 23958263
TI  - Increases in creatine kinase with atorvastatin treatment are not associated with
      decreases in muscular performance.
AB  - BACKGROUND: The present study examined if increases in creatine kinase (CK)
      levels during high-dose atorvastatin treatment are associated with changes in
      skeletal muscle function and symptoms. METHODS: The Effect of Statins on Muscle
      Performance study (STOMP) investigated the effects of atorvastatin 80 mg daily
      for 6 months on muscle performance, exercise capacity, and the incidence of
      statin-associated muscle complaints in healthy adults. RESULTS: CK levels
      increased with atorvastatin (n = 202) from 132.3 +/- 120.9 U/L (mean +/- SD) at
      baseline to 159.7 +/- 170.4 and 153.1 +/- 139.4 U/L at 3 and 6 months,
      respectively (P <= 0.002 for both). Changes in CK with atorvastatin treatment
      were not associated with changes in muscle function or the incidence of myalgia.
      More subjects on atorvastatin (n = 24) compared to placebo (n = 12 of 217)
      doubled their CK level at 6 months (P = 0.02). No differences in muscle function
      or physical activity were observed between atorvastatin-treated subjects who did
      or did not double their CK. CONCLUSIONS: Results of the present investigation
      extend the findings of STOMP by demonstrating that greater increases in CK levels
      with high-dose atorvastatin treatment did not deleteriously impact skeletal
      muscle function or predict skeletal muscle complaints. This study was registered
      at ClinicalTrials.gov (NCT00609063).

PMID- 23958264
TI  - The effect of exercise training on ankle-brachial index in type 2 diabetes.
AB  - INTRODUCTION: Though being physically active has associated with a healthier
      ankle-brachial index (ABI) in observational studies, ABI usually does not change
      with exercise training in patients with peripheral artery disease (PAD). Less is
      known about the effect of exercise training on ABI in patients without PAD but at
      high risk due to the presence of type 2 diabetes (T2DM). METHODS: Participants (n
      = 140) with uncomplicated T2DM, and without known cardiovascular disease or PAD,
      aged 40-65 years, were randomized to supervised aerobic and resistance training 3
      times per week for 6 months or to a usual care control group. ABI was measured
      before and after the intervention. RESULTS: Baseline ABI was 1.02 +/- 0.02 in
      exercisers and 1.03 +/- 0.01 in controls (p = 0.57). At 6 months, exercisers vs.
      controls improved ABI by 0.04 +/- 0.02 vs. -0.03 +/- 0.02 (p = 0.001). This
      change was driven by an increase in ankle pressures (p < 0.01) with no change in
      brachial pressures (p = 0.747). In subgroup analysis, ABI increased in exercisers
      vs. controls among those with baseline ABI <1.0 (0.14 +/- 0.03 vs. 0.02 +/- 0.02,
      p = 0.004), but not in those with a baseline ABI >=1.0 (p = 0.085). The
      prevalence of ABI between 1.0 and 1.3 increased from 63% to 78% in exercisers and
      decreased from 62% to 53% in controls. Increased ABI correlated with decreased
      HbA1c, systolic and diastolic blood pressure, but the effect of exercise on ABI
      change remained significant after adjustment for these changes (beta = 0.061, p =
      0.004). CONCLUSION: These data suggest a possible role for exercise training in
      the prevention or delay of PAD in T2DM, particularly among those starting with an
      ABI <1.0. Clinicaltrials.gov Registry Number: NCT00212303.

PMID- 23958265
TI  - Endothelium-specific insulin resistance leads to accelerated atherosclerosis in
      areas with disturbed flow patterns: a role for reactive oxygen species.
AB  - OBJECTIVE: Systemic insulin resistance is associated with a portfolio of risk
      factors for atherosclerosis development. We sought to determine whether insulin
      resistance specifically at the level of the endothelium promotes atherosclerosis
      and to examine the potential involvement of reactive oxygen species. METHODS: We
      cross-bred mice expressing a dominant negative mutant human insulin receptor
      specifically in the endothelium (ESMIRO) with ApoE(-/-) mice to examine the
      effect of endothelium-specific insulin resistance on atherosclerosis. RESULTS:
      ApoE(-/-)/ESMIRO mice had similar blood pressure, plasma lipids and whole-body
      glucose tolerance, but blunted endothelial insulin signalling, in comparison to
      ApoE(-/-) mice. Atherosclerosis was significantly increased in ApoE(-/-)/ESMIRO
      mice at the aortic sinus (226 +/- 16 versus 149 +/- 24 * 10(3) MUm(2), P = 0.01)
      and lesser curvature of the aortic arch (12.4 +/- 1.2% versus 9.4 +/- 0.9%, P =
      0.035). Relaxation to acetylcholine was blunted in aorta from ApoE(-/-)/ESMIRO
      mice (Emax 65 +/- 41% versus 103 +/- 6%, P = 0.02) and was restored by the
      superoxide dismutase mimetic MnTMPyP (Emax 112 +/- 15% versus 65 +/- 41%, P =
      0.048). Basal generation of superoxide was increased 1.55 fold (P = 0.01) in
      endothelial cells from ApoE(-/-)/ESMIRO mice and was inhibited by the NADPH
      oxidase inhibitor gp91ds-tat (-12 +/- 0.04%, P = 0.04), the NO synthase inhibitor
      L-NMMA (-8 +/- 0.02%, P = 0.001) and the mitochondrial specific inhibitor
      rotenone (-23 +/- 0.04%, P = 0.006). CONCLUSIONS: Insulin resistance specifically
      at the level of the endothelium leads to acceleration of atherosclerosis in areas
      with disturbed flow patterns such as the aortic sinus and the lesser curvature of
      the aorta. We have identified a potential role for increased generation of
      reactive oxygen species from multiple enzymatic sources in promoting
      atherosclerosis in this setting.

PMID- 23958266
TI  - Comparison of predictive performance of various fatty acids for the risk of
      cardiovascular disease events and all-cause deaths in a community-based cohort.
AB  - BACKGROUND: The issue of whether saturated fats and trans fats are superior
      predictors of all-cause death and cardiovascular disease than n-3 polyunsaturated
      fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),
      remains a matter of contention. Furthermore, few studies have examined the
      relationship between fatty acids and the outcomes of cardiovascular disease (CVD)
      in Asian populations. The aim of this study was to compare the effectiveness of
      various plasma fatty acids as predictors for all-cause death and CVD events in an
      ethnic Chinese population. METHODS: This study assembled a community-based
      prospective cohort, comprising 1833 participants (60.6 +/- 10.5 yrs, 44.5% women)
      who underwent a comprehensive evaluation of fatty acids in blood using gas
      chromatography. None of the subjects had a history of CVD at the time of
      recruitment. RESULTS: A total of 568 individuals died and 275 individuals
      developed CVD during the follow-up period (median of 9.6 years; interquartile
      range of 8.9-10.5 years). Following adjustment for established cardiovascular
      risk factors, the relative risk of all-cause death in the highest quartile,
      compared with the lowest quartile, was 1.33 for saturated fats (95% confidence
      interval [CI], 1.01-1.75, test for trend, P = 0.015), 1.71 for trans fats (95%
      CI, 1.27-2.31, test for trend, P = 0.0003), 0.77 for EPA (95% CI, 0.59-1.00, test
      for trend, P = 0.048), and 0.89 for DHA (95% CI, 0.68-1.18, test for trend, P =
      0.354). Similar patterns were observed for CVD events. Trans fats presented the
      largest area under the receiver operator characteristic curve (0.740, 95% CI,
      0.716-0.766) for the prediction of all-cause death. A mutually adjusted two
      marker model indicated that saturated fats and trans fats were significant
      predictors of all-cause death and CVD; however, the other fatty acids were not.
      In addition, trans fats presented the greatest improvement in net
      reclassification for all-cause death (7.7%, P = 0.003), followed by EPA (3.8%, P
      = 0.033). Saturated fats presented the greatest improvement in net
      reclassification for CVD events (5.6%, P = 0.039). CONCLUSIONS: Our data provides
      strong evidence to support that plasma saturated fats and trans fats can predict
      all-cause death and CVD more effectively than other fatty acid markers.

PMID- 23958267
TI  - Regulation of antioxidant system, lipids and fatty acid beta-oxidation
      contributes to the cardioprotective effect of sodium tanshinone IIA sulphonate in
      isoproterenol-induced myocardial infarction in rats.
AB  - OBJECTIVE: Myocardial infarction (MI) is a cause of high morbidity and mortality
      in the world. Sodium tanshinone IIA sulphonate (STS) has been well used in
      Oriental medicine for treating cardiovascular diseases, however, the underlying
      mechanisms remain unclear. Alterations of circulating lipid profiles, increased
      fatty acid beta-oxidation and oxidative stress play most important roles in the
      pathogenesis of MI. The present study aims to elucidate whether STS possesses
      cardioprotective effect against MI driven by isoproterenol (ISO), and to
      investigate its potential mechanisms of action. METHODS: MI was induced by
      subcutaneous injection of ISO (85 mg/kg at interval of 24 h for 2 consecutive
      days) to rats. The rats were randomly divided into 6 groups: (1) control; (2)
      ISO; (3) STS (16 mg/kg) +control; (4-6) STS (16, 8, 4 mg/kg) +ISO. RESULTS: Our
      study showed that STS could ameliorate cardiac dysfunction and variation of
      myocardial zymogram, up-regulate antioxidant systems, and maintain the levels of
      circulating lipids driven by supramaximal doses ISO as well. Moreover, modulation
      of redox-sensitive extracellular signal-regulated kinase1/2 (ERK1/2)/Nuclear
      factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and AMP
      activated protein kinase (AMPK)/acetyl CoA carboxylase (ACC)/carnitine
      palmitoyltransferase (CPT) 1 pathways were involved in STS induced
      cardioprotection. CONCLUSIONS: STS exerts strong favorable cardioprotective
      action. Additionally, the properties of STS, such as anti-dyslipidemia, anti
      oxidant and inhibition of fatty acid beta-oxidation, may be the mechanisms
      underlying the observed results.

PMID- 23958268
TI  - Independent associations of low 25 hydroxy vitamin D and high parathyroid
      hormonal levels with nonalcoholic fatty liver disease in Asian Indians residing
      in north India.
AB  - OBJECTIVE: We analysed the associations of 25 hydroxy vitamin D [25(OH) D] and
      parathyroid hormone (PTH) levels with clinical, anthropometric, biochemical and
      body composition parameters in Asian Indians with nonalcoholic fatty liver
      disease (NAFLD). METHODS: In this case-control study, 162 cases and 173 age and
      sex matched controls were recruited. Clinical, anthropometric, biochemical
      parameters and liver ultrasound were done. Percentage body fat (%BF), lean body
      mass and bone mineral density (BMD) were assessed by dual energy X-ray
      absorptiometry (DXA). Fasting insulin levels, value of homeostasis model
      assessment of insulin resistance (HOMA-IR), serum 25(OH) D, calcium and PTH
      levels were measured. RESULTS: Subjects with NAFLD had lower serum 25(OH) D (19.4
      +/- 8.5 vs. 27.8 +/- 9.4 ng/ml, p = 0.0001) and higher serum PTH (54.9 +/- 19.5
      vs.41.5 +/- 18.3 pg/ml, p = 0.0001) levels as compared to controls. We observed
      significantly high values of systolic blood pressure (p = 0.002), waist
      circumference (p = 0.05), serum triglycerides (p = 0.002), total cholesterol (p =
      0.002), alanine transaminase (p = 0.05), fasting insulin (p = 0.02) and HOMA-IR
      (p = 0.03) in the lowest 25(OH) D quartile. Multivariable-logistic regression
      showed that low serum 25(OH) D [OR (95%CI): 4.46 (2.58-7.72), p = 0.0001] and
      high PTH [OR (95%CI): 2.21 (1.50-3.30), p = 0.0001] level were independently
      associated with NAFLD. CONCLUSION: Low serum 25(OH) D and high PTH levels were
      independently associated with the presence of NAFLD in Asian Indians residing in
      north India.

PMID- 23958269
TI  - Everolimus therapy is associated with reduced lipoprotein-associated
      phospholipase A2 (Lp-Pla2) activity and oxidative stress in heart transplant
      recipients.
AB  - BACKGROUND: Several studies demonstrated decreased severity and incidence of
      cardiac allograft vasculopathy (CAV) in heart transplant recipients receiving
      immunosuppressive therapy with everolimus. However, data regarding the influence
      of everolimus on risk factors predisposing to CAV are hitherto limited. We here
      systematically evaluated cardiovascular risk factors in heart transplanted
      patients, who underwent conversion to everolimus or were maintained on
      conventional therapy with calcineurin inhibitors (CNI). METHODS: 50 Patients
      receiving everolimus and 91 patients receiving CNI in addition to mycophenolate
      mofetil and low-dosed steroids were included in the study. CAV risk factors were
      determined in plasma or urine using standard enzymatic or immunochemical methods.
      RESULTS: No significant differences were observed between both groups with regard
      to lipid (total, LDL- and HDL-cholesterol), metabolic (glucose, insulin),
      inflammatory (C-reactive protein, IL-6, myeloperoxidase) and cardiac (troponin I,
      NT-proBNP) risk factors. However, significantly lower activity of lipoprotein
      associated phospholipase A2 (Lp-PLA2) and a negative correlation between the Lp
      PLA2 activity and the everolimus concentration were observed in plasmas from
      everolimus-treated patients. Conversion to everolimus significantly lowered Lp
      PLA2 activity in heart transplant recipients. Studies in vitro revealed reduced
      Lp-PLA2 expression in hepatocytes and macrophages pre-exposed to everolimus. In
      addition, reduced plasma markers of oxidative stress including oxidized LDL, 8
      iso-prostaglandin F2alpha and protein carbonyls were noted in heart transplant
      recipients receiving everolimus therapy. CONCLUSION: Our results suggest that
      everolimus specifically lowers plasma activity and cellular production of Lp-PLA2
      and thereby dampens oxidative stress. These effects may additionally contribute
      to the reduced CAV incidence observed in heart transplant recipients receiving
      everolimus therapy.

PMID- 23958270
TI  - Low-cost equilibrium unfolding of heme proteins using 2 MUl samples.
AB  - Equilibrium unfolding experiments provide access to protein thermodynamic
      stability revealing basic aspects of protein structure-function relationships. A
      limitation of these experiments stands on the availability of large amounts of
      protein samples. Here we present the use of the NanoDrop for monitoring
      guanidinium chloride-induced unfolding by Soret absorbance of monomeric heme
      proteins. Unfolding experiments using 2 MUl of reactant are validated by
      fluorescence and circular dichroism spectroscopy and supported with five heme
      proteins including neuroglobin, cytochrome b5, and cyanoglobin. This work
      guarantees 2 orders of magnitude reduction in protein expense. Promising low-cost
      protein unfolding experiments following other chromophores and high-throughput
      screenings are discussed.

PMID- 23958271
TI  - Steroids or pentoxifylline for alcoholic hepatitis (STOPAH): study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Alcoholic hepatitis is the most florid presentation of alcohol
      related liver disease. In its severe form, defined by a Maddrey's discriminant
      function (DF) >=32, the 28-day mortality rate is approximately 35%. A number of
      potential treatments have been subjected to clinical trials, of which two,
      corticosteroids and pentoxifylline, may have therapeutic benefit. The role of
      corticosteroids is controversial as trial results have been inconsistent, whereas
      the role of pentoxifylline requires confirmation as only one previous placebo
      controlled trial has been published. METHODS/DESIGN: STOPAH is a multicentre,
      double-blind, factorial (2 * 2) trial in which patients are randomised to one of
      four groups:1. Group A: placebo / placebo2. Group B: placebo / prednisolone3.
      Group C: pentoxifylline / placebo4. Group D: pentoxifylline / prednisoloneThe
      trial aims to randomise 1,200 patients with severe alcoholic hepatitis, in order
      to provide sufficient power to determine whether either of the two interventions
      is effective. The primary endpoint of the study is mortality at 28 days, with
      secondary endpoints being mortality at 90 days and 1 year. DISCUSSION: STOPAH
      aims to be a definitive study to resolve controversy around the existing
      treatments for alcoholic hepatitis. Eligibility criteria are based on clinical
      parameters rather than liver biopsy, which are aligned with standard clinical
      practice in most hospitals. The use of a factorial design will allow two
      treatments to be evaluated in parallel, with efficient use of patient numbers to
      achieve high statistical power. TRIAL REGISTRATION: EudraCT reference number:
      2009-013897-42 ISRCTN reference number: ISRCTN88782125.

PMID- 23958272
TI  - 'Doing the hard yards': carer and provider focus group perspectives of accessing
      Aboriginal childhood disability services.
AB  - BACKGROUND: Despite a high prevalence of disability, Aboriginal Australians
      access disability services in Australia less than non-Aboriginal Australians with
      a disability. The needs of Aboriginal children with disability are particularly
      poorly understood. They can endure long delays in treatment which can impact
      adversely on development. This study sought to ascertain the factors involved in
      accessing services and support for Aboriginal children with a disability.
      METHODS: Using the focus group method, two community forums, one for health and
      service providers and one for carers of Aboriginal children with a disability,
      were held at an Aboriginal Community Controlled Health Service (ACCHS) in the
      Sydney, metropolitan area of New South Wales, Australia. Framework analysis was
      applied to qualitative data to elucidate key issues relevant to the dimensions of
      access framework. Independent coding consistency checks were performed and
      consensus of analysis verified by the entire research team, several of whom
      represented the local Aboriginal community. RESULTS: Seventeen health and social
      service providers representing local area government and non-government-funded
      health and social service organisations and five carers participated in two
      separate forums between September and October 2011. Lack of awareness of services
      and inadequate availability were prominent concerns in both groups despite
      geographic proximity to a major metropolitan area with significant health
      infrastructure. Carers noted racism, insufficient or non-existent services, and
      the need for an enhanced role of ACCHSs and AHWs in disability support services.
      Providers highlighted logistical barriers and cultural and historical issues that
      impacted on the effectiveness of mainstream services for Aboriginal people.
      CONCLUSIONS: Despite dedicated disability services in an urban community,
      geographic proximity does not mitigate lack of awareness and availability of
      support. This paper has enumerated a number of considerations to address
      provision of disability services in an urban Australian Aboriginal community
      including building expertise and specialist capacity within Aboriginal Health
      Worker positions and services.Increasing awareness of services, facilitating
      linkages and referrals, eliminating complexities to accessing support, and
      working with families and Aboriginal community organisations within a framework
      of resilience and empowerment to ensure a relevant and acceptable model are
      necessary steps to improving support and care for Aboriginal children with a
      disability.

PMID- 23958273
TI  - Decreased IGF-1 levels potentiate association of inflammation with all-cause and
      cardiovascular mortality in prevalent hemodialysis patients.
AB  - OBJECTIVE: Insulin-like growth factor-1 (IGF-1) and inflammation have both been
      linked to high cardiovascular risk and mortality in the general population, as
      well as in hemodialysis (HD) patients. We hypothesized that the association of
      low IGF-1 with chronic inflammation may increase the mortality risk in HD
      patients. DESIGN: We investigated the interactions between inflammatory
      biomarkers (IL-6 and TNF-alpha) and IGF-1 as predictors of death over a 4 years
      of follow-up (median--47 months, interquartile range--17.5-75 months) in 96
      prevalent HD patients (35% women, mean age of 64.9 +/- 11.6 years). RESULTS: A
      significant interaction effect of low IGF-1 (defined as a level less than median)
      and high IL-6 (defined as a level higher than median) on all-cause and
      cardiovascular mortality was found: crude Cox hazard ratios (HR) for the product
      termed IGF-1 * IL-6 were 4.27, with a 95% confidence interval (CI): 2.10 to 8.68
      (P<0.001) and 7.49, with a 95% CI: 2.40-24.1 (P=0.001), respectively. Across the
      four IGF-1-IL-6 categories, the group with low IGF-1 and high IL-6 exhibited the
      worse outcome in both all-cause and cardiovascular mortality (multivariable
      adjusted hazard ratios were 4.92, 95% CI 1.86 to 13.03, and 14.34, 95% CI 1.49 to
      137.8, respectively). The main clinical characteristics of patients in the low
      IGF-1-high IL-6 group didn't differ from other IGF-1-IL-6 categorized groups
      besides gender that consequently was inserted in all multivariable models
      together with the other potential confounders. CONCLUSIONS: An increase in
      mortality risk was observed in HD patients with low IGF-1 and high IL-6 levels,
      especially cardiovascular causes.

PMID- 23958274
TI  - Early parenteral lipids and growth velocity in extremely-low-birth-weight
      infants.
AB  - BACKGROUND & AIMS: Whether early parenteral lipids improve postnatal growth of
      preterm neonates remains unclear. We aimed to assess the effects of parenteral
      lipids on growth velocity in extremely-low-birth-weight infants. METHODS: This
      retrospective cohort study included 121 extremely-low-birth-weight infants. The
      associations between parenteral lipids (cumulative intakes during the first week
      and delays in their introduction) and growth velocities (weight, head
      circumference and length) up to 28 days of life and to 36 weeks of corrected age
      were analysed using uni- and multivariate linear regression. RESULTS: Univariate
      analyses showed a significant positive association between the cumulative intakes
      of parenteral lipids during the first week and i) weight gain up to day 28; ii)
      weight gain up to 36 weeks of corrected age; iii) head circumference growth up to
      day 28. There was a negative correlation between the delay in parenteral lipid
      introduction and weight gain up to day 28. In multivariate analyses, the
      association between the cumulative intakes of parenteral lipids and weight gain
      up to 28 days was independent of gestational age at birth, birth weight, sex,
      smallness for gestational age, and enteral intakes (regression coefficient: 0.19;
      95% CI: 0.01-0.38) and, up to 36 weeks, independent of gestational age, birth
      weight, sex, smallness for gestational age and parenteral glucose and amino acids
      (0.16; 95% CI: 0.04-0.27). CONCLUSIONS: Parenteral lipids during the first week
      were positively associated with weight gain in extremely-low-birth-weight infants
      and could improve early nutritional support of preterm neonates.

PMID- 23958275
TI  - Peak plasma anti-Xa levels after first and third doses of enoxaparin in women
      receiving weight-based thromboprophylaxis following caesarean section: a
      prospective cohort study.
AB  - BACKGROUND: Women undergoing caesarean section are at higher risk for
      thromboembolic complications following delivery than other parturients. The aim
      of this study was to determine whether higher doses of enoxaparin based on body
      weight are safe and more likely to achieve plasma anti-Xa levels within the
      accepted thromboprophylactic range. METHODS: We undertook a prospective cohort
      study of 80 women undergoing caesarean section in a tertiary obstetric hospital
      with >6000 deliveries per year. Enoxaparin was administered after caesarean
      section using the Royal College of Obstetricians and Gynaecologists weight
      adjusted dosing guidelines. Plasma anti-Xa levels were measured at baseline and 3
      4 h after enoxaparin administration on days one and three postoperatively. The
      main outcomes of interest were plasma anti-Xa levels and the proportion of
      patients with plasma anti-Xa levels in the range of 0.2-0.4 IU/mL. RESULTS: The
      proportion of women with anti-Xa levels between 0.2 and 0.4 IU/mL was 72% (95% CI
      60-81%). Unadjusted mean anti-Xa levels were 0.26 +/- 0.09 IU/mL and 0.28 +/-
      0.08 IU/mL on day one and day three respectively. No woman had levels >0.48
      IU/mL. CONCLUSION: The majority of women receiving weight-based enoxaparin
      thromboprophylaxis following caesarean section achieved plasma anti-Xa levels
      within the putative thromboprophylactic range. No woman achieved levels
      associated with an increased risk of bleeding (>0.8 IU/mL). These findings
      provide a safety basis for a large prospective study using this regimen.

PMID- 23958276
TI  - UK survey of the availability of cell salvage and interventional radiological
      services for the management of obstetric haemorrhage.

PMID- 23958277
TI  - The use of cell salvage in women undergoing cesarean hysterectomy for abnormal
      placentation.
AB  - BACKGROUND: Although transfusion of autologous blood obtained from cell salvage
      has increased, its role in obstetric practice remains controversial. This case
      series reports the use of cell salvage in an attempt to avoid allogeneic
      transfusion in women undergoing cesarean hysterectomy for placenta accreta.
      METHODS: This prospective observational study, conducted in a large public
      maternity hospital, included 41 women with an antenatal diagnosis of placenta
      accreta, of whom 20 underwent cesarean hysterectomy and 15 received autologous
      blood after cell salvage. Intraoperative cell salvage was used for autologous
      blood transfusion, and salvaged blood was monitored for prewash and
      postfiltration squamous cells, fetal hemoglobin, and potassium concentration. Pre
      and postoperative hemoglobin, platelet count and coagulation profile were
      compared. RESULTS: Twenty women underwent caesarean hysterectomy. Cell-salvaged
      blood was collected in 18 women and re infused in 15 women (83.3%). The mean
      volume of reinfused salvaged blood was 1476 +/- 247 mL. Mean potassium
      concentrations (1.4 +/- 1.2 versus 3.7 +/- 0.42 mEq/L) and median squamous cell
      counts (0 [0-1] versus 8 [3-12]/high power field) were significantly lower
      postfiltration compared to prewash values. There were no instances of
      intraoperative or postoperative amniotic fluid embolism, hypotension, sepsis or
      coagulopathy. Of the 15 women who received autologous blood, 13 (86.7%) did not
      require allogeneic red blood cell transfusion. CONCLUSIONS: Autologous
      transfusion of salvaged blood can be used to minimize allogeneic transfusion in
      women undergoing cesarean hysterectomy for placenta accreta.

PMID- 23958278
TI  - Differentiation of nerve fibers storing CGRP and CGRP receptors in the peripheral
      trigeminovascular system.
AB  - Primary headaches such as migraine are postulated to involve the activation of
      sensory trigeminal pain neurons that innervate intracranial blood vessels and the
      dura mater. It is suggested that local activation of these sensory nerves may
      involve dural mast cells as one factor in local inflammation, causing
      sensitization of meningeal nociceptors. Immunofluorescence was used to study the
      detailed distribution of calcitonin gene-related peptide (CGRP) and its receptor
      components calcitonin receptor-like receptor (CLR) and receptor activity
      modifying protein 1 (RAMP1) in whole-mount rat dura mater and in human dural
      vessels. The relative distributions of CGRP, CLR, and RAMP1 were evaluated with
      respect to each other and in relationship to mast cells, myelin, substance P,
      neuronal nitric oxide synthase, pituitary adenylate cyclase-activating
      polypeptide, and vasoactive intestinal peptide. CGRP expression was found in thin
      unmyelinated fibers, whereas CLR and RAMP1 were expressed in thicker myelinated
      fibers coexpressed with an A-fiber marker. CLR and RAMP1 immunoreactivity
      colocalized with mast cell tryptase in rodent; however, expression of both
      receptor components was not observed in human mast cells. Immunoreactive
      substance P fibers coexpressed CGRP, although neuronal nitric oxide synthase and
      vasoactive intestinal peptide expression was very limited, and these fibers were
      distinct from the CGRP-positive fibers. Few pituitary adenylate cyclase
      activating polypeptide immunoreactive fibers occurred and some colocalized with
      CGRP. PERSPECTIVE: This study demonstrates the detailed distribution of CGRP and
      its receptor in the dura mater. These data suggest that CGRP is expressed in C
      fibers and may act on A-fibers, rodent mast cells, and vascular smooth muscle
      cells that express the CGRP receptor. These sites represent potential
      pathophysiological targets of novel antimigraine agents such as the newly
      developed CGRP receptor antagonists.

PMID- 23958279
TI  - Beta-adrenergic receptor mechanisms and pain sensitivity in women with
      menstrually related mood disorders.
AB  - Somatic symptoms experienced by women with a menstrually related mood disorder
      (MRMD) during their premenstrual luteal phase contribute to functional
      impairment. Yet, investigations on pathophysiological mechanisms contributing to
      heightened pain sensitivity in MRMD are sparse. During the luteal phase, 61 women
      with an MRMD and 61 non-MRMD controls were evaluated for beta-adrenergic receptor
      (beta-AR) responsivity using the isoproterenol sensitivity test. A subset (43
      MRMD and 50 non-MRMD) then entered a double-blind, placebo-controlled, crossover
      protocol to examine the effect of beta-AR blockade with intravenous propranolol
      on sensitivity to experimental (cold pressor and ischemic) and clinical (McGill
      Pain Questionnaire score) pain. Women with an MRMD exhibited greater beta1- and
      beta2-AR responsivity, ischemic pain intensity, and affective clinical pain
      ratings than controls. Propranolol increased cold pressor pain tolerance in both
      groups, but it decreased cold pain intensity and ischemic pain unpleasantness
      ratings only in non-MRMD women. In contrast, propranolol decreased affective
      ratings of clinical pain in women with MRMD. Exploratory analyses indicated that
      only in MRMD women did greater beta-AR responsivity predict greater sensitivity
      to cold pressor and ischemic pain. This study provides the first evidence for a
      role of beta-AR mechanisms in the hyperalgesia and clinical pain experienced by
      women with MRMDs. PERSPECTIVE: This article describes the effects of beta
      adrenergic receptor stimulation and blockade on experimental and clinical pain
      sensitivity in women with an MRMD. The results of this study may have
      implications for the management of the substantial somatic premenstrual
      symptomatology experienced by women with an MRMD.

PMID- 23958280
TI  - A comparative study of Toxoplasma gondii seroprevalence in three healthy Chinese
      populations detected using native and recombinant antigens.
AB  - BACKGROUND: Toxoplasmosis is one of the most common parasitic zoonoses. The
      seroprevalence of Toxoplasma gondii infection in humans varies widely worldwide.
      Detection of Toxoplasma-specific antibodies has been a gold standard method for
      both epidemiological investigation and clinical diagnosis. Genetic investigation
      indicated that there is a wide distribution of different genome types or variants
      of the parasite prevalent in different areas. Thus the reliability of using
      antigens from parasites of a single genome type for diagnosis and epidemiology
      purposes needs to be extensively evaluated. METHODS: In this study, the
      prevalence of T. gondii infection among 880 clinically healthy individuals in
      China was systematically tested using crude soluble native antigens and purified
      recombinant antigens of type I and II T. gondii. The T. gondii-specific IgG and
      IgM in the sera was further confirmed using commercial Toxoplasmosis Diagnosis
      Kits and Western blot assays. RESULTS: The sero-prevalence of T. gondii-specific
      IgG detected with crude native Type I and type II antigens was 12.2% and 11.3%
      respectively. Whereas the overall prevalence was more than 20% when combined with
      the results obtained with recombinant tachyzoite and bradyzoite antigens. There
      was an obvious variation in immune-recognition of parasite antigens among the
      individuals studied. CONCLUSIONS: The general prevalence of anti-T. gondii IgG in
      the study population was likely much higher than previously reported. The data
      also suggested that there is more genetic diversity among the T. gondii isolates
      in China. Further, combination of recombinant antigens with clear immuno
      recognition will be able to generate more sensitive diagnostic results than those
      obtained with crude antigens of T. gondii tachyzoites.

PMID- 23958281
TI  - Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human
      liver function.
AB  - BACKGROUND: Interindividual differences in liver functions such as protein
      synthesis, lipid and carbohydrate metabolism and drug metabolism are influenced
      by epigenetic factors. The role of the epigenetic machinery in such processes
      has, however, been barely investigated. 5-hydroxymethylcytosine (5hmC) is a
      recently re-discovered epigenetic DNA modification that plays an important role
      in the control of gene expression. RESULTS: In this study, we investigate 5hmC
      occurrence and genomic distribution in 8 fetal and 7 adult human liver samples in
      relation to ontogeny and function. LC-MS analysis shows that in the adult liver
      samples 5hmC comprises up to 1% of the total cytosine content, whereas in all
      fetal livers it is below 0.125%. Immunohistostaining of liver sections with a
      polyclonal anti-5hmC antibody shows that 5hmC is detected in most of the
      hepatocytes. Genome-wide mapping of the distribution of 5hmC in human liver
      samples by next-generation sequencing shows significant differences between fetal
      and adult livers. In adult livers, 5hmC occupancy is overrepresented in genes
      involved in active catabolic and metabolic processes, whereas 5hmC elements which
      are found in genes exclusively in fetal livers and disappear in the adult state,
      are more specific to pathways for differentiation and development. CONCLUSIONS:
      Our findings suggest that 5-hydroxymethylcytosine plays an important role in the
      development and function of the human liver and might be an important determinant
      for development of liver diseases as well as of the interindividual differences
      in drug metabolism and toxicity.

PMID- 23958283
TI  - Effect of cognitive-behavioral group therapy for panic disorder in changing
      coping strategies.
AB  - BACKGROUND: Cognitive-behavioral group therapy (CBGT) is an efficient treatment
      for panic disorder (PD). However, the role of CBGT in enhancing strategies to
      cope with stressful events has not been established. AIM: To evaluate the effect
      of CBGT on the choice of coping strategy by PD patients compared to a group of
      individuals without mental disorders. METHODS: Forty-eight PD patients who
      completed a 12-session CBGT protocol were compared to 75 individuals without
      mental disorders regarding coping strategies as evaluated by the Coping
      Strategies Inventory (CSI). The severity of PD was assessed at baseline and after
      CBGT through the Clinical Global Impression (CGI) scale, the Hamilton Anxiety
      Scale (HAM-A), and the Panic Inventory (PI). RESULTS: Treatment was effective in
      reducing PD severity in all outcome measures. Patients used significantly fewer
      confrontation, escape and avoidance strategies after CBGT. The use of more
      adaptive coping strategies was related to a decrease in panic attacks and
      anticipatory anxiety. Application of the CSI showed that the use of strategies
      was also significantly different in patients as compared to the control group,
      except for escape and avoidance, which became similar after the CBGT protocol.
      CONCLUSIONS: Despite the changes observed after the CBGT protocol, the choice of
      coping strategy was still different in patients vs. controls. The current CBGT
      protocol was used specifically to assess PD symptoms. Other cognitive tools
      should be included to address maladaptive coping strategies.

PMID- 23958282
TI  - A place for play? The influence of the home physical environment on children's
      physical activity and sedentary behaviour.
AB  - The home environment is an important influence on the sedentary behaviour and
      physical activity of children, who have limited independent mobility and spend
      much of their time at home. This article reviews the current evidence regarding
      the influence of the home physical environment on the sedentary behaviour and
      physical activity of children aged 8-14 years. A literature search of peer
      reviewed articles published between 2005 and 2011 resulted in 38 observational
      studies (21 with activity outcomes, 23 with sedentary outcomes) and 11
      experimental studies included in the review. The most commonly investigated
      behavioural outcomes were television watching and moderate to vigorous physical
      activity. Media equipment in the home and to a lesser extent the bedroom were
      positively associated with children's sedentary behaviour. Physical activity
      equipment and the house and yard were not associated with physical activity,
      although environmental measures were exclusively self-reported. On the other
      hand, physical activity equipment was inversely associated with sedentary
      behaviours in half of studies. Observational studies that investigated the
      influence of the physical and social environment within the home space, found
      that the social environment, particularly the role of parents, was important.
      Experimental studies that changed the home physical environment by introducing a
      television limiting device successfully decreased television viewing, whereas the
      influence of introducing an active video game on activity outcomes was
      inconsistent. Results highlight that the home environment is an important
      influence on children's sedentary behaviour and physical activity, about which
      much is still unknown. While changing or controlling the home physical
      environment shows promise for reducing screen based sedentary behaviour, further
      interventions are needed to understand the broader impact of these changes.
      Future studies should prioritise investigating the influence of the home physical
      environment, and its interaction with the social environment, on objectively
      measured sedentary time and home context specific behaviours, ideally including
      technologies that allow objective measures of the home space. 

PMID- 23958284
TI  - Gastrointestinal nematodes in grazing dairy cattle from small and medium-sized
      farms in southern Poland.
AB  - This study aimed to estimate the prevalence of gastrointestinal nematodes and the
      intensity of infection in grazing dairy cattle from small and medium-sized farms
      in southern Poland. The level of antibodies against Ostertagia ostertagi in the
      bulk tank milk (BTM) from the animals was also assessed. Rectal fecal samples
      collected from 361 cows on 20 farms were examined using Willis-Schlaaf flotation
      and the McMaster method. BTM samples were tested for the presence of O. ostertagi
      antibodies using ELISA. Multiplex PCR was used to identify the third-stage larvae
      (L3) of gastrointestinal nematodes derived from the culture of pooled fecal
      samples from sampled farms. Gastrointestinal nematode eggs were found in the
      samples from 18 of the 20 herds with a prevalence range from 20.4 to 94.5%. The
      average number of eggs excreted in the feces of the herds was 200 eggs per gram
      (EPG). Antibodies to O. ostertagi were found in 20 of the examined herds (100%),
      of which 6 had optical density ratios (ODR) greater than 0.5. PCR results showed
      the presence of three nematode species: Ostertagia ostertagi, Cooperia oncophora
      and Oesophagostomum radiatum. 

PMID- 23958285
TI  - [Transforaminal lumbar interbody fusion: goals of the minimal invasive approach].
AB  - BACKGROUND AND PURPOSE: Transforaminal lumbar interbody fusion (TLIF) is an
      effective technique, which can achieve a fusion rate of up to 90%. The minimally
      invasive approach has become increasingly popular because it is able to minimize
      iatrogenic soft tissue and muscle injury. Although the minimally invasive TLIF
      technique has gained popularity, its effectiveness compared with open TLIF has
      yet to be established. The authors prospectively compared the outcomes of
      patients who underwent mini-open TLIF with patients who underwent open TLIF.
      METHODS: Between 2007 and 2008, 50 patients underwent TLIF for grade 1
      spondylolisthesis; 25 mini-open TLIF and 25 open TLIF. The mean age in each group
      was 48years, and there was no statistically significant difference between the
      groups. Data were collected perioperatively. Pain and functional disability were
      measured using a visual analogue scale (VAS) and the Oswestry disability index
      (ODI) at 3months, 6months, 1year and 2years. In addition, foraminal and disc
      height were measured at the same intervals and the fusion was evaluated at 1year
      on CT-scan. Soft tissue damage was evaluated by measuring the serum myoglobin and
      creatine phosphokinase activity. RESULTS: The mean VAS improved from 7 to 2.8 and
      the ODI decreased from 30/50 to 15/50 and fusion rate at 1 year was 98%. There
      was no statistical difference for the clinical and radiological outcomes between
      the groups. The mean operative time was 186min for the open group, 170min for the
      mini-open group (P<0.05) and the mean blood loss was 486mL for the open group and
      148mL for the mini-open group (P<0.01). CONCLUSION: The mini-open TLIF procedure
      for symptomatic low grade spondylolisthesis is an effective option which achieves
      similar clinical and radiological outcomes and reduces perioperative morbidity as
      well as soft tissue damage.

PMID- 23958286
TI  - Pediatric idiopathic intracranial hypertension: a need for clarification.

PMID- 23958287
TI  - Acute toe walking with viral myositis.

PMID- 23958288
TI  - Acute bilateral ptosis as the sole manifestation of neurocysticercosis in a
      child.

PMID- 23958289
TI  - Does regional compared to local anaesthesia influence outcome after arteriovenous
      fistula creation?
AB  - BACKGROUND: An arteriovenous fistula is the optimal form of vascular access in
      patients with end-stage renal failure requiring haemodialysis. Unfortunately,
      approximately one-third of fistulae fail at an early stage. Different anaesthetic
      techniques can influence factors associated with fistula success, such as
      intraoperative blood flow and venous diameter. A regional anaesthetic brachial
      plexus block results in vasodilatation and improved short- and long-term fistula
      flow compared to the infiltration of local anaesthetic alone. This, however, has
      not yet been shown in a large trial to influence long-term fistula patency, the
      ultimate clinical measure of success.The aim of this study is to compare whether
      a regional anaesthetic block, compared to local anaesthetic infiltration, can
      improve long-term fistula patency. METHODS: This study is an observer-blinded,
      randomised controlled trial. Patients scheduled to undergo creation of either
      brachial or radial arteriovenous fistulae will receive a study information sheet,
      and consent will be obtained in keeping with the Declaration of Helsinki.
      Patients will be randomised to receive either: (i) an ultrasound guided brachial
      plexus block using lignocaine with adrenaline and levobupivicaine, or (ii) local
      anaesthetic infiltration with lignocaine and levobupivicaine.A total of 126
      patients will be recruited. The primary outcome is fistula primary patency at
      three months. Secondary outcomes include primary patency at 1 and 12 months,
      secondary patency and fistula flow at 1, 3 and 12 months, flow on first
      haemodialysis, procedural pain, patient satisfaction, change in cephalic vein
      diameter pre- and post-anaesthetic, change in radial or brachial artery flow pre-
      and post-anaesthetic, alteration of the surgical plan after anaesthesia as guided
      by vascular mapping with ultrasound, and fistula infection requiring antibiotics.
      CONCLUSIONS: No large randomised controlled trial has examined the influence of
      brachial plexus block compared with local anaesthetic infiltration on the long
      term patency of arteriovenous fistulae. If the performance of brachial plexus
      block increases fistulae patency, this will have significant clinical and
      financial benefits as the number of patients able to commence haemodialysis when
      planned should increase, and the number of "redo" or revision procedures should
      be reduced. TRIAL REGISTRATION: This study has been approved by the West of
      Scotland Research Ethics Committee 5 (reference no. 12/WS/0199) and is registered
      with the ClinicalTrials.gov database (reference no. NCT01706354).

PMID- 23958291
TI  - Towards understanding infertility: inflammatory mediators in male reproductive
      tract.

PMID- 23958290
TI  - Glycan-based biomarkers for mucopolysaccharidoses.
AB  - The mucopolysaccharidoses (MPS) result from attenuation or loss of enzyme
      activities required for lysosomal degradation of the glycosaminoglycans,
      hyaluronan, heparan sulfate, chondroitin/dermatan sulfate, and keratan sulfate.
      This review provides a summary of glycan biomarkers that have been used to
      characterize animal models of MPS, for diagnosis of patients, and for monitoring
      therapy based on hematopoietic stem cell transplantation and enzyme replacement
      therapy. Recent advances have focused on the non-reducing terminus of the
      glycosaminoglycans that accumulate as biomarkers, using a combination of
      enzymatic digestion with bacterial enzymes followed by quantitative liquid
      chromatography/mass spectrometry. These new methods provide a simple, rapid
      diagnostic strategy that can be applied to samples of urine, blood, cerebrospinal
      fluid, cultured cells and dried blood spots from newborn infants. Analysis of the
      non-reducing end glycans provides a method for monitoring enzyme replacement and
      substrate reduction therapies and serves as a discovery tool for uncovering novel
      biomarkers and new forms of mucopolysaccharidoses. 

PMID- 23958292
TI  - Maternal molecular features and gene profiling of monocytes during first
      trimester pregnancy.
AB  - We examined the molecular characteristics of monocytes of pregnant and non
      pregnant women to investigate the molecular effects that are associated with
      immunoregulation at the maternal-fetal interface. We analyzed molecular features
      and target genes in monocytes of pregnant women using flow cytometry, real-time
      PCR and oligonucleotide microarray technology. CD14(high) monocytes and several
      immune gene members including CD200, CD200R, IDO, IFI27, IL-10 and G0S2 were
      found to be differentially expressed in monocytes throughout pregnancy. In
      addition, transcripts within components of the signaling cascade of immune cells
      (HLA-DRB4, HBEGF, IL-8, CD3D, CCL5), and of several transcription factors (SOCS1,
      CXCL10, ID1, ID2) were altered in the monocytes of pregnant women. Further
      studies will be needed to elucidate the biological significance of our
      observation. 

PMID- 23958293
TI  - Combined measurement of perfusion, venous oxygen saturation, and skeletal muscle
      T2* during reactive hyperemia in the leg.
AB  - BACKGROUND: The function of the peripheral microvascular may be interrogated by
      measuring perfusion, tissue oxygen concentration, or venous oxygen saturation
      (SvO2) recovery dynamics following induced ischemia. The purpose of this work is
      to develop and evaluate a magnetic resonance (MR) technique for simultaneous
      measurement of perfusion, SvO2, and skeletal muscle T2*. METHODS: Perfusion,
      Intravascular Venous Oxygen saturation, and T2* (PIVOT) is comprised of
      interleaved pulsed arterial spin labeling (PASL) and multi-echo gradient-recalled
      echo (GRE) sequences. During the PASL post-labeling delay, images are acquired
      with a multi-echo GRE to quantify SvO2 and T2* at a downstream slice location.
      Thus time-courses of perfusion, SvO2, and T2* are quantified simultaneously
      within a single scan. The new sequence was compared to separately measured PASL
      or multi-echo GRE data during reactive hyperemia in five young healthy subjects.
      To explore the impairment present in peripheral artery disease patients, five
      patients were evaluated with PIVOT. RESULTS: Comparison of PIVOT-derived data to
      the standard techniques shows that there was no significant bias in any of the
      time-course-derived metrics. Preliminary data show that PAD patients exhibited
      alterations in perfusion, SvO2, and T2* time-courses compared to young healthy
      subjects. CONCLUSION: Simultaneous quantification of perfusion, SvO2, and T2* is
      possible with PIVOT. Kinetics of perfusion, SvO2, and T2* during reactive
      hyperemia may help to provide insight into the function of the peripheral
      microvasculature in patients with PAD.

PMID- 23958294
TI  - Interactions between alphaCaMKII and calmodulin in living cells: conformational
      changes arising from CaM-dependent and -independent relationships.
AB  - BACKGROUND: alphaCaMKII plays central and essential roles in long-term
      potentiation (LTP), learning and memory. alphaCaMKII is activated via binding
      with Ca2+/CaM in response to elevated Ca2+ concentration. Furthermore, prolonged
      increase in Ca2+ concentration leads to the auto-phosphorylation of alphaCaMKII
      at T286, maintaining the activation of alphaCaMKII even after Ca2+/CaM
      dissociation. Importantly, the active form of alphaCaMKII is thought to exhibit
      conformational change. In order to elucidate the relationships between the
      interaction of alphaCaMKII with CaM and the conformational change of alphaCaMKII,
      we generated molecular probes (YFP-alphaCaMKII with CFP-CaM and YFP-alphaCaMKII
      CFP) and performed time-lapse imaging of the interaction with CaM and the
      conformational change, respectively, in living cells using FRET. RESULTS: The
      interaction of YFP-alphaCaMKII with CFP-CaM and the conformational change of YFP
      alphaCaMKII-CFP were induced simultaneously in response to increased
      concentrations of Ca2+. Consistent with previous predictions, high levels of Ca2+
      signaling maintained the conformational change of YFP-alphaCaMKII-CFP at the time
      when CFP-CaM was released from YFP-alphaCaMKII. These observations indicated the
      transfer of alphaCaMKII conformational change from CaM-dependence to CaM
      independence. Furthermore, analyses using alphaCaMKII mutants showed that
      phosphorylation at T286 and T305/306 played positive and negative roles,
      respectively, during in vivo interaction with CaM and further suggested that CaM
      dependent and CaM-independent conformational changed forms displays similar but
      distinct structures. CONCLUSIONS: Importantly, these structual differences
      between CaM-dependent and -independent forms of alphaCaMKII may exhibit
      differential functions for alphaCaMKII, such as interactions with other molecules
      required for LTP and memory. Our molecular probes could thus be used to identify
      therapeutic targets for cognitive disorders that are associated with the
      misregulation of alphaCaMKII.

PMID- 23958295
TI  - Measuring levels of person-centeredness in acute care of older people with
      cognitive impairment: evaluation of the POPAC scale.
AB  - BACKGROUND: Person-centeredness is increasingly advocated in the literature as a
      gold-standard, best practice concept in health services for older people. This
      concept describes care that incorporates individual and multidimensional needs,
      personal biography, subjectivity and interpersonal relationships. However, acute
      in-patient hospital services have a long-standing biomedical tradition that may
      contrast with person-centred care. Since few tools exist that enable measurements
      of the extent to which acute in-patient hospital services are perceived as being
      person-centred, this study aimed to translate the English version of the Person
      centred care of older people with cognitive impairment in acute care scale
      (POPAC) to Swedish, and evaluate its psychometric properties in a sample of acute
      hospital staff. METHODS: The 15-item POPAC was translated, back-translated and
      culturally adjusted, and distributed to a cross-sectional sample of Swedish acute
      care staff (n = 293). Item performance was evaluated through assessment of item
      means, internal consistency by Cronbach's alpha on total and on subscale levels;
      temporal stability was assessed through Pearson's product correlation and intra
      class correlation between test and retest scores. Confirmatory factor analysis
      was used to explore model fit. RESULTS: The results indicate that the Swedish
      version POPAC provides a tentatively construct-valid and reliable contribution to
      measuring the extent to which acute in-patient hospital services have processes
      and procedures that can facilitate person-centred care of older patients with
      cognitive impairment. However, some questions remain regarding the dimensionality
      of POPAC. CONCLUSIONS: POPAC provides a valuable contribution to the quest of
      improving acute care for older patients with cognitive impairment by enabling
      measures and subsequent accumulation of internationally comparable data for
      research and practice development purposes. POPAC can be used to highlight
      strengths and areas for improvements in care practice for older patients, and to
      illuminate aspects that risk being overlooked in busy acute hospital settings.

PMID- 23958296
TI  - Predictability of spontaneous thoracic curve correction after anterior
      thoracolumbar correction and fusion in adolescent idiopathic scoliosis. A
      retrospective study on a consecutive series of 29 patients with a minimum follow
      up of 2 years.
AB  - BACKGROUND CONTEXT: According to the Lenke classification, a Type 5 adolescent
      idiopathic scoliosis can be surgically treated with selective anterior
      thoracolumbar or lumbar fusion. PURPOSE: This study aims to predict the
      spontaneous correction of the unfused thoracic curve after anterior thoracolumbar
      fusion and to study whether age is of influence on this predictability. STUDY
      DESIGN: Retrospective study on a consecutive series of patients. PATIENT SAMPLE:
      Of a consecutive series of 38 patients with idiopathic thoracolumbar scoliosis,
      Lenke type 5, 29 patients were included in the study. All patients were treated
      with anterior spinal fusion and instrumentation. A minimum follow-up of 2 years
      was available for all patients (mean, 4 years; range, 2-17 years). To investigate
      the influence of age on the outcome, we divided the group into two subgroups: an
      adolescent (n=13) and an adult age group (n=16). The mean age in the adolescent
      group was 17 (range, 13-21 years) and 38 years (range, 22-54 years) in the adult
      group. OUTCOME MEASURES: Physiological measures include coronal Cobb angle,
      apical vertebral translation (AVT) and apical vertebral rotation (AVR), shoulder
      tilt, trunk shift, L4 tilt, and pelvic tilt. Relative corrections were computed
      for the thoracolumbar and thoracic curves in each patient using the following
      formula: (preoperative curve-postoperative curve)/preoperative curve*100 (%). The
      correlation coefficient between the relative (%) corrections of the thoracic and
      thoracolumbar curves was calculated for the whole group as for the two age
      subgroups. METHODS: For radiographic evaluation, we used standing anteroposterior
      and lateral projections of the thoracolumbar spine to determine Cobb angle, AVT
      and AVR, and coronal balance. RESULTS: Both the thoracolumbar and thoracic curves
      in the whole group improved after surgery (45% and 19%, respectively, p<.01). In
      the adolescent age group, a significant correlation between the relative (%)
      correction of the thoracolumbar curve and the relative (%) correction of the
      thoracic curve was found (R=0.704; p=.01) and between age and relative (%)
      correction of the thoracic curve (R=-0.805; p<.01). CONCLUSIONS: These results
      show that the spontaneous correction of the thoracic curve is a reflection of the
      thoracolumbar curve correction in adolescent thoracolumbar idiopathic scoliosis.
      Moreover, the predictability of the thoracic curve correction in the individual
      patient seems to decrease with increasing age of the patient.

PMID- 23958297
TI  - Strain distribution in the lumbar vertebrae under different loading
      configurations.
AB  - BACKGROUND CONTEXT: The stress/strain distribution in the human vertebrae has
      seldom been measured, and only for a limited number of loading scenarios, at few
      locations on the bone surface. PURPOSE: This in vitro study aimed at measuring
      how strain varies on the surface of the lumbar vertebral body and how such strain
      pattern depends on the loading conditions. METHODS: Eight cadaveric specimens
      were instrumented with eight triaxial strain gauges each to measure the magnitude
      and direction of principal strains in the vertebral body. Each vertebra was
      tested in a three adjacent vertebrae segment fashion. The loading configurations
      included a compressive force aligned with the vertebral body but also tilted (15
      degrees ) in each direction in the frontal and sagittal planes, a traction force,
      and torsion (both directions). Each loading configuration was tested six times on
      each specimen. RESULTS: The strain magnitude varied significantly between strain
      measurement locations. The strain distribution varied significantly when
      different loading conditions were applied (compression vs. torsion vs. traction).
      The strain distribution when the compressive force was tilted by 15 degrees  was
      also significantly different from the axial compression. Strains were minimal
      when the compressive force was applied coaxial with the vertebral body, compared
      with all other loading configurations. Also, strain was significantly more
      uniform for the axial compression, compared with all other loading
      configurations. Principal strains were aligned within 19 degrees  to the axis of
      the vertebral body for axial-compression and axial-traction. Conversely, when the
      applied force was tilted by 15 degrees , the direction of principal strain varied
      by a much larger angle (15 degrees  to 28 degrees ). CONCLUSIONS: This is the
      first time, to our knowledge, that the strain distribution in the vertebral body
      is measured for such a variety of loading configurations and a large number of
      strain sensors. The present findings suggest that the structure of the vertebral
      body is optimized to sustain compressive forces, whereas even a small tilt angle
      makes the vertebral structure work under suboptimal conditions.

PMID- 23958298
TI  - Citrus nobiletin suppresses inducible nitric oxide synthase gene expression in
      interleukin-1beta-treated hepatocytes.
AB  - BACKGROUND: Nobiletin is a polymethoxylated flavone that is abundant in the peels
      of citrus fruits, such as Citrus unshiu (Satsuma mandarin) and Citrus sinensis.
      The dried peels of C. unshiu (chinpi) have been included in several formulae of
      Japanese Kampo medicines. Nobiletin may suppress the induction of inducible
      nitric oxide synthase (iNOS), which synthesizes the inflammatory mediator nitric
      oxide (NO) in hepatocytes. METHODS: A C. unshiu peel (CUP) extract was prepared.
      Primary cultured rat hepatocytes were treated with the CUP extract or nobiletin
      in the presence of interleukin 1beta (IL-1beta), which induces iNOS expression.
      NO production and iNOS gene expression were analyzed. RESULTS: High-performance
      liquid chromatography analyses revealed that the nobiletin content in the CUP
      extract was 0.14%. Nobiletin dose-dependently reduced the NO levels and decreased
      iNOS expression at the protein, mRNA and antisense transcript levels. Flavone,
      which does not contain any methoxy groups, also suppressed iNOS induction.
      Nobiletin reduced the transcriptional activity of iNOS promoter-luciferase
      constructs and the DNA-binding activity of nuclear factor kappaB (NF-kappaB) in
      the nuclei. CONCLUSIONS: The suppression of iNOS induction by nobiletin suggests
      that nobiletin may be responsible for the anti-inflammatory effects of citrus
      peels and have a therapeutic potential for liver diseases.

PMID- 23958299
TI  - A study on human serum albumin influence on glycation of fibrinogen.
AB  - Although in vivo glycation proceeds in complex mixture of proteins, previous
      studies did not take in consideration the influence of protein-protein
      interaction on Maillard reaction. The aim of our study was to test the influence
      of human serum albumin (HSA) on glycation of fibrinogen. The isotopic labeling
      using [(13)C6] glucose combined with LC-MS were applied as tool for
      identification possible glycation sites in fibrinogen and for evaluation the
      effect of HSA on the glycation level of selected amino acids in fibrinogen. The
      obtained data indicate that the addition of HSA protects the fibrinogen from
      glycation. The level of glycation in presence of HSA is reduced by 30-60% and
      depends on the location of glycated residue in sequence of protein.

PMID- 23958300
TI  - Capsaicin stimulates glucose uptake in C2C12 muscle cells via the reactive oxygen
      species (ROS)/AMPK/p38 MAPK pathway.
AB  - Capsaicin has been reported to regulate blood glucose levels and to ameliorate
      insulin resistance in obese mice. This study demonstrates that capsaicin
      increases glucose uptake directly by activating AMP-activated protein kinase
      (AMPK) in C2C12 muscle cells, which manifested as an attenuation of glucose
      uptake when compound C, an AMPK inhibitor, was co-administered with capsaicin.
      However, the insulin signaling molecules insulin receptor substrate-1 (IRS-1) and
      Akt were not affected by capsaicin. Additional results showed that p38 mitogen
      activated protein kinase (MAPK) is also involved in capsaicin-induced glucose
      transport downstream of AMPK because capsaicin increased p38 MAPK phosphorylation
      significantly and its specific inhibitor SB203580 inhibited capsaicin-mediated
      glucose uptake. Treatment with an AMPK inhibitor reduced p38 MAPK
      phosphorylation, but the p38 MAPK inhibitor had no effect on AMPK. Capsaicin
      stimulated ROS generation in C2C12 muscle cells, and when ROS were captured using
      the nonspecific antioxidant NAC, the increase in both capsaicin-induced AMPK
      phosphorylation and capsaicin-induced glucose uptake was attenuated, suggesting
      that ROS function as an upstream activator of AMPK. Taken together, these results
      suggest that capsaicin, independent of insulin, increases glucose uptake via ROS
      generation and consequent AMPK and p38 MAPK activations.

PMID- 23958301
TI  - Reduction of E-cadherin by human defensin-5 in esophageal squamous cells.
AB  - Barrett's esophagus (BE) is metaplastic columnar epithelium converted from normal
      squamous epithelia in the distal esophagus that is thought to be a precancerous
      lesion of esophageal adenocarcinoma. BE is attributed to gastroesophageal reflux
      disease (GERD), and therefore gastric acid or bile acids are thought to be
      factors that cause epithelial cell damage and inflammation in the gastro
      esophageal junction. The decrease of adherent junction molecules, E-cadherin has
      been reported to be associated with the progression of the Barrett's carcinoma,
      but the initiation of BE is not sufficiently understood. BE is characterized by
      the presence of goblet cells and occasionally Paneth cells are observed at the
      base of the crypts. The Paneth cells possess dense granules, in which human
      antimicrobial peptide human defensin-5 (HD-5) are stored and secreted out of the
      cells. This study determined the roles of HD-5 produced from metaplastic Paneth
      cells against adjacent to squamous cells in the gastro-esophageal junction. A
      human squamous cell line Het-1A, was incubated with the synthetic HD-5 peptide as
      a model of squamous cell in the gastro-esophageal junctions, and alterations of E
      cadherin were investigated. Immunocytochemistry, flowcytometry, and Western
      blotting showed that the expression of E-cadherin protein was decreased. And a
      partial recovery from the decrease was observed by treatment with a
      CD10/neprilysin inhibitor (thiorphan). In conclusion, E-cadherin expression in
      squamous cells was reduced by HD-5 using in vitro experiments. In gastro
      esophageal junction, HD-5 produced from metaplastic Paneth cells may therefore
      accelerate the initiation of BE.

PMID- 23958302
TI  - Thyroid hormone receptor inhibits hepatoma cell migration through transcriptional
      activation of Dickkopf 4.
AB  - Triiodothyronine (T3) is a potent form of thyroid hormone mediates several
      physiological processes including cellular growth, development, and
      differentiation via binding to the nuclear thyroid hormone receptor (TR). Recent
      studies have demonstrated critical roles of T3/TR in tumor progression. Moreover,
      long-term hypothyroidism appears to be associated with the incidence of human
      hepatocellular carcinoma (HCC), independent of other major HCC risk factors.
      Dickkopf (DKK) 4, a secreted protein that antagonizes the canonical Wnt signaling
      pathway, is induced by T3 at both mRNA and protein levels in HCC cell lines.
      However, the mechanism underlying T3-mediated regulation of DKK4 remains unknown.
      In the present study, the 5' promoter region of DKK4 was serially deleted, and
      the reporter assay performed to localize the T3 response element (TRE).
      Consequently, we identified an atypical direct repeat TRE between nucleotides 
      1645 and -1629 conferring T3 responsiveness to the DKK4 gene. This region was
      further validated using chromatin immunoprecipitation (ChIP) and electrophoretic
      mobility shift assay (EMSA). Stable DKK4 overexpression in SK-Hep-1 cells
      suppressed cell invasion and metastatic potential, both in vivo andin vitro, via
      reduction of matrix metalloproteinase-2 (MMP-2) expression. Our findings
      collectively suggest that DKK4 upregulated by T3/TR antagonizes the Wnt signal
      pathway to suppress tumor cell progression, thus providing new insights into the
      molecular mechanism underlying thyroid hormone activity in HCC.

PMID- 23958303
TI  - A voltage-gated pore for translocation of tRNA.
AB  - Very little is known about how nucleic acids are translocated across membranes.
      The multi-subunit RNA Import Complex (RIC) from mitochondria of the kinetoplastid
      protozoon Leishmania tropica induces translocation of tRNAs across artificial or
      natural membranes, but the nature of the translocation pore remains unknown. We
      show that subunits RIC6 and RIC9 assemble on the membrane in presence of subunit
      RIC4A to form complex R3. Atomic Force Microscopy of R3 revealed particles with
      an asymmetric surface groove of ~20 nm rim diameter and ~1 nm depth. R3 induced
      translocation of tRNA into liposomes when the pH of the medium was lowered to ~6
      in the absence of ATP. R3-mediated tRNA translocation could also be induced at
      neutral pH by a K(+) diffusion potential with an optimum of 60-70 mV. Point
      mutations in the Cys2-His2 Fe-binding motif of RIC6, which is homologous to the
      respiratory Complex III Fe-S protein, abrogated import induced by low pH but not
      by K(+) diffusion potential. These results indicate that the R3 complex forms a
      pore that is gated by a proton-generated membrane potential and that the Fe-S
      binding region of RIC6 has a role in proton translocation. The tRNA import
      complex of L. tropica thus contains a novel macromolecular channel distinct from
      the mitochondrial protein import pore that is apparently involved in tRNA import
      in some species.

PMID- 23958304
TI  - Wnt/beta-catenin signaling regulates neuronal differentiation of mesenchymal stem
      cells.
AB  - Mesenchymal stem cells (MSCs) have been demonstrated to be able to differentiate
      into neuron-like cells, but the precise mechanisms controlling this process are
      unclear. Using neuron-specific enolase (NSE) and nestin as neuronal markers, we
      examined the role of Wnt/beta-catenin signaling in MSC neuronal differentiation
      in present study. The results indicated that the expression of beta-catenin
      increased markedly during the neuronal differentiation of MSCs. Blocking Wnt
      signaling by treating MSCs with beta-catenin siRNA could decrease the
      differentiation of MSCs into neuron-like cells and up-regulation of Wnt signaling
      by treating MSCs with Wnt-3a could promote neuronal differentiation of MSCs.
      Above results suggest that Wnt/beta-catenin signaling may play a pivotal role in
      neuronal differentiation of MSCs. Our data broaden the knowledge of molecular
      mechanisms involved in the neuronal differentiation of MSCs and provide a
      potential target for directing differentiation of MSCs for clinical application. 

PMID- 23958305
TI  - P2X7 receptors regulate engulfing activity of non-stimulated resting astrocytes.
AB  - We previously demonstrated that P2X7 receptors (P2X7Rs) expressed by cultured
      mouse astrocytes were activated without any exogenous stimuli, but its roles in
      non-stimulated resting astrocytes remained unknown. It has been reported that
      astrocytes exhibit engulfing activity, and that the basal activity of P2X7Rs
      regulates the phagocytic activity of macrophages. In this study, therefore, we
      investigated whether P2X7Rs regulate the engulfing activity of mouse astrocytes.
      Uptake of non-opsonized beads by resting astrocytes derived from ddY-mouse cortex
      time-dependently increased, and the uptaken beads were detected in the
      intracellular space. The bead uptake was inhibited by cytochalasin D (CytD), an F
      actin polymerization inhibitor, and agonists and antagonists of P2X7Rs apparently
      decreased the uptake. Spontaneous YO-PRO-1 uptake by ddY-mouse astrocytes was
      reduced by the agonists and antagonists of P2X7Rs, but not by CytD. Down
      regulation of P2X7Rs using siRNA decreased the bead uptake by ddY-mouse
      astrocytes. In addition, compared to in the case of ddY-mouse astrocytes, SJL
      mouse astrocytes exhibited higher YO-PRO-1 uptake activity, and their bead uptake
      was significantly greater. These findings suggest that resting astrocytes exhibit
      engulfing activity and that the activity is regulated, at least in part, by their
      P2X7Rs.

PMID- 23958306
TI  - Mos1 transposon-based transformation of fish cell lines using baculoviral
      vectors.
AB  - Drosophila Mos1 belongs to the mariner family of transposons, which are one of
      the most ubiquitous transposons among eukaryotes. We first determined nuclear
      transportation of the Drosophila Mos1-EGFP fusion protein in fish cell lines
      because it is required for a function of transposons. We next constructed
      recombinant baculoviral vectors harboring the Drosophila Mos1 transposon or
      marker genes located between Mos1 inverted repeats. The infectivity of the
      recombinant virus to fish cells was assessed by monitoring the expression of a
      fluorescent protein encoded in the viral genome. We detected transgene expression
      in CHSE-214, HINAE, and EPC cells, but not in GF or RTG-2 cells. In the co
      infection assay of the Mos1-expressing virus and reporter gene-expressing virus,
      we successfully transformed CHSE-214 and HINAE cells. These results suggest that
      the combination of a baculovirus and Mos1 transposable element may be a tool for
      transgenesis in fish cells.

PMID- 23958307
TI  - PROmiRNA: a new miRNA promoter recognition method uncovers the complex regulation
      of intronic miRNAs.
AB  - The regulation of intragenic miRNAs by their own intronic promoters is one of the
      open problems of miRNA biogenesis. Here, we describe PROmiRNA, a new approach for
      miRNA promoter annotation based on a semi-supervised statistical model trained on
      deepCAGE data and sequence features. We validate our results with existing
      annotation, PolII occupancy data and read coverage from RNA-seq data. Compared to
      previous methods PROmiRNA increases the detection rate of intronic promoters by
      30%, allowing us to perform a large-scale analysis of their genomic features, as
      well as elucidate their contribution to tissue-specific regulation. PROmiRNA can
      be downloaded from http://promirna.molgen.mpg.de. 

PMID- 23958308
TI  - Clinical application of the Melbourne risk prediction tool in a high-risk upper
      abdominal surgical population: an observational cohort study.
AB  - OBJECTIVES: (1) To determine the ability of the Melbourne risk prediction tool to
      predict a pulmonary complication as defined by the Melbourne Group Scale in a
      medically defined high-risk upper abdominal surgery population during the
      postoperative period; (2) to identify the incidence of postoperative pulmonary
      complications; and (3) to examine the risk factors for postoperative pulmonary
      complications in this high-risk population. DESIGN: Observational cohort study.
      SETTING: Tertiary Australian referral centre. PARTICIPANTS AND METHODS: 50
      individuals who underwent medically defined high-risk upper abdominal surgery.
      Presence of postoperative pulmonary complications was screened daily for seven
      days using the Melbourne Group Scale (Version 2). Postoperative pulmonary risk
      prediction was calculated according to the Melbourne risk prediction tool.
      OUTCOME MEASURES: (1) Melbourne risk prediction tool; and (2) the incidence of
      postoperative pulmonary complications. RESULTS: Sixty-six percent (33/50)
      underwent hepatobiliary or upper gastrointestinal surgery. Mean (SD) anaesthetic
      duration was 377.8 (165.5) minutes. The risk prediction tool classified 84%
      (42/50) as high risk. Overall postoperative pulmonary complication incidence was
      42% (21/50). The tool was 91% sensitive and 21% specific with a 50% chance of
      correct classification. CONCLUSION: This is the first study to externally
      validate the Melbourne risk prediction tool in an independent medically defined
      high-risk population. There was a higher incidence of pulmonary complications
      postoperatively observed compared to that previously reported. Results
      demonstrated poor validity of the tool in a population already defined medically
      as high risk and when applied postoperatively. This observational study has
      identified several important points to consider in future trials.

PMID- 23958309
TI  - Omic-profiling in breast cancer metastasis to bone: implications for mechanisms,
      biomarkers and treatment.
AB  - Despite well-recognised advances in breast cancer treatment, there remain
      substantial numbers of patients who develop metastatic disease, of which up to
      70% involves spread to bone, resulting in skeletal complications which have a
      major negative impact on mortality and quality of life. Bisphosphonates and newer
      bone-targeted agents have reduced the prevalence of skeletal complications, yet
      there remains significant unmet clinical need, particularly for the development
      of more specific therapies for the prevention and treatment of metastatic bone
      disease, for the prediction of risk of its development in individual patients and
      for the prediction of response to treatments. Modern 'omic' strategies can
      potentially make a major contribution to meeting this need. Technological
      advances in the field of nucleic acid sequencing, mass spectrometry and metabolic
      profiling have driven progress in genomics, transcriptomics (functional
      genomics), proteomics and metabolomics. This review appraises the recent
      application of these approaches to studies of breast cancer metastasis
      (particularly to bone), with a focus on understanding how omic approaches may
      lead to new therapeutic options and to novel biomarker molecules or molecular
      signatures with potential value in clinical practise. The increasingly recognised
      need for rigorous sample quality control and both pre-clinical and clinical
      validation to meet the ultimate goals of clinical utility and patient benefit is
      discussed. Future directions of omic driven research in breast cancer metastasis
      are considered, in particular micro-RNAs and their role in the post
      transcriptional regulation of gene function and the possible role of cancer-stem
      cells and epigenetic modifications in the development of distant metastases. 

PMID- 23958310
TI  - Second-line treatment options in metastatic castration-resistant prostate cancer:
      a comparison of key trials with recently approved agents.
AB  - Standard first-line treatment for metastatic castration-resistant prostate cancer
      (mCRPC) is docetaxel plus prednisone; however, patients will usually experience
      disease progression during or after docetaxel treatment due to inherent or
      acquired resistance. Before 2010, second-line options for mCRPC were limited.
      However, cabazitaxel, abiraterone acetate and enzalutamide have since been
      approved for patients with mCRPC whose disease has progressed during or after
      receiving docetaxel, based on the Phase III trials TROPIC, COU-AA-301 and AFFIRM.
      In all three trials, an overall survival benefit (primary endpoint) was seen in
      the experimental arm compared with the control arm: 15.1 vs. 12.7months for
      cabazitaxel plus prednisone compared with mitoxantrone plus prednisone in TROPIC
      (hazard ratio [HR] 0.70; P<0.0001); 14.8 vs. 10.9months for abiraterone
      acetateplus prednisone compared with placebo plus prednisone in COU-AA-301 (HR
      0.65; P<0.001); and 18.4 vs. 13.6months for enzalutamide compared with placebo
      alone in AFFIRM (0.63; P<0.001). However, differences in patient populations,
      comparators, and selection and/or definition of secondary endpoints make it
      difficult to draw direct cross-trial comparisons. Radium-223 dichloride has also
      been approved for patients with mCRPC with metastases to bone but not other
      organs. To date, no comparative trials or sequencing studies with newer agents
      have been performed. Without such data, treatment decisions must be based on
      evaluation of the existing evidence. This commentary compares and contrasts study
      designs and key data from each of these Phase III trials, and also discusses
      recent and ongoing clinical trials with new agents in the first- and second-line
      settings in mCRPC. 

PMID- 23958311
TI  - Foreword - In honor of Prof. em. Dr. Hans Peter Merkle on the occasion of his
      70th birthday.

PMID- 23958312
TI  - Bridging material and biological sciences: the legacy of Hans Peter Merkle.

PMID- 23958313
TI  - Is there a future for cell-penetrating peptides in oligonucleotide delivery?
AB  - Cell-penetrating peptides have been widely investigated as delivery vehicles for
      oligonucleotides (e.g., siRNA and antisense oligonucleotides). Different delivery
      strategies can be used, such as co-incubation, direct conjugation, non-covalent
      complex, and modification on the surface of liposome or polymer complexes.
      However, several challenges remain for their preclinical and clinical
      development. Endosomal escape, lack of cell/tissue specificity, and toxicity are
      major concerns in the design of cell-penetrating peptide-mediated delivery
      systems. In this commentary, we highlight recent reports of cell-penetrating
      peptide incorporation into oligonucleotide delivery systems and underline the
      remaining challenges, particularly for preclinical and clinical applications. 

PMID- 23958314
TI  - Cell penetrating peptides fail to induce an innate immune response in epithelial
      cells in vitro: implications for continued therapeutic use.
AB  - Cell penetrating peptides (CPPs) offer the exciting potential of effectively
      delivering macromolecules to the cytoplasm of a cell that are otherwise
      impermeable to the plasma membrane. Although the use of these peptides has so far
      been well tolerated in clinical trials, it is important to remember that some of
      these CPPs were originally derived from pathogenic material. We therefore sought
      to determine if three of the most widely studied CPPs; HIV-TAT, Antennapedia and
      Transportan, initiated an immune response in epithelial cells. Using conditions
      where these peptides efficiently delivered a rhodamine tagged BSA cargo to the
      interior of epithelial cells, we failed to observe an effect on cell viability as
      determined by MTT assay (P>0.05). Further, CPP-mediated delivery of this protein
      cargo failed to activate NFkappaB, which would be indicative of toll-like
      receptor signalling. Finally, no significant increase in the release of the
      inflammatory cytokines interleukin (IL)-8 and IL-6 was detected in epithelial
      cells exposed to CPP complexes for 72 h (P>0.05). Together, these results
      indicate that these commonly used CPPs are passive carriers that do not initiate
      epithelial cell-associated 'danger signals' during the process of cytoplasmic
      delivery of a model protein cargo.

PMID- 23958315
TI  - The role of CDX2 in Caco-2 cell differentiation.
AB  - BACKGROUND: CDX2 plays a key part in the differentiation of Caco-2 cells, a colon
      carcinoma derived cell line that undergoes spontaneous differentiation. The
      effect of CDX2 expression in Caco-2 cells over time in culture has not been
      studied yet on a genome-wide level. METHODS: The impact of CDX2 expression on the
      genomic profile of Caco-2 cells was studied by transducing cells with CDX2
      targeting shRNAs. Knockdown efficiency was assessed on mRNA level and protein
      level by RTPCR, microarrays, and Western blots. Gene set enrichment analysis was
      performed to assess regulation of specific gene sets. RESULTS: CDX2 expression
      had an inhibitory effect on the transcriptional activity of beta-catenin/TCF at
      early stages of culturing, while at later stages, its role in the trans
      activation of target genes specific for small intestinal enterocytes seemed more
      dominant. CONCLUSIONS: The unique induction of a small intestinal signature upon
      differentiation in Caco-2 cells seems to be at least partially under the control
      of CDX2.

PMID- 23958316
TI  - Mechanistic basis for unexpected bioavailability enhancement of polyelectrolyte
      complexes incorporating BCS class III drugs and carrageenans.
AB  - The objective of this study was to investigate the potential of lambda
      carrageenan to work as an absorption modifying excipient in combination with
      formulations of BCS class 3 substances. Trospium chloride was used as a model BCS
      class 3 substance. Polyelectrolyte complexes of trospium and lambda-carrageenan
      were produced by layer-by-layer complexation. A lambda-carrageenan-containing
      formulation was administered either in capsules size 9 to rats by gavage or
      directly into ligated intestinal loops of rats. Exceptionally strong variations
      were observed in the plasma concentrations of the rats that received lambda
      carrageenan compared to the control group, but enhanced plasma concentrations
      were observed only in some of the rats. In vitro permeability studies were
      performed across Caco2-monolayers and across excised segments of rat jejunum in a
      modified Ussing chamber to learn more about the mechanism of absorption
      enhancement. The complex did not show any effect in Caco2-cells, but led to a
      major enhancement of permeability across excised segments in modified Ussing
      chambers. Carrageenan did not lead to alterations of tight junctions. The
      bioavailability enhancing effect thus was most likely due to an interaction of
      the polyelectrolyte-drug complex with the mucus, which provided an intimate
      contact between the drug and the absorbing surface. A similar effect was also
      achievable with other types of carrageenan and was also transferable to other
      compounds. In conclusion, lambda-carrageenan-drug complexes show interesting
      excipient-drug-epithelium interactions - however, for full utilization of the
      permeation enhancing potential, an intimate and reproducible contact between
      absorbing epithelia and the complex is needed. 

PMID- 23958317
TI  - Influence of methionine oxidation on the aggregation of recombinant human growth
      hormone.
AB  - Oxidation of methionine (Met) residues is one of the major chemical degradations
      of therapeutic proteins. This chemical degradation can occur at various stages
      during production and storage of a biotherapeutic drug. During the oxidation
      process, the side chain of methionine residue undergoes a chemical modification,
      with the thioether group substituted by a sulfoxide group. In previous papers, we
      showed that oxidation of the two most accessible methionine residues of
      recombinant human growth hormone (r-hGH), Met14 and Met125, has no influence on
      the conformation of the protein [1]. However, the oxidized r-hGH is less
      thermally stable than the native protein [2]. In the current work, the
      consequences of the oxidation of these two methionine residues on the aggregation
      of r-hGH were investigated. The aggregation properties and kinetics of the native
      and oxidized r-hGH were measured in different buffers with both spectroscopic and
      chromatographic methods. Stabilities of oxidized and non-oxidized r-hGH were
      studied after storage at 37 degrees C and freeze/thawing cycles. Methionine
      oxidation influenced the aggregation properties of r-hGH. In accelerated
      stability studies at 37 degrees C, oxidized hormone aggregated more and faster
      than non-oxidized hormone. In freezing/thawing stability studies, it was found
      that oxidized r-hGH was less stable than its non-oxidized counterpart. In case of
      hGH, we have shown that chemical degradations such as oxidation can affect its
      physical stability and can induce aggregation.

PMID- 23958318
TI  - Insulin-like growth factor-I aerosol formulations for pulmonary delivery.
AB  - Injectable insulin-like growth factor-1 (IGF-I) is therapeutically deployed for
      severe IGF-I deficiency and clinically explored for various other indications
      such as muscle wasting disease. In the present study, liquid IGF-I formulations
      for pulmonal application were screened with regard to buffer type (acetate,
      citrate, histidine, and succinate), sodium chloride concentration (50-150 mM),
      and pH value (4.5-6.5). Methionine 59 oxidation (Met(o)) was observed in acetate
      buffer along with reducible dimer and trimer formation at low pH. Oxidation
      correlated with formation of covalent, reducible aggregates, and complete loss of
      potency was observed for severely aggregated samples. Bioactivity was partly
      retained in cases where complete oxidation but limited aggregation was found. In
      contrast, IGF-I integrity was preserved in histidine buffer during accelerated
      stability. After delivery from air-jet or vibrating-mesh nebulizers, limited
      Met(o) formation and no aggregation was observed. Nebulization performance
      regarding aerosol output rate, mass median aerodynamic diameter, and fine
      particle fraction for liquid IGF-I formulation was comparable to 0.9% sodium
      chloride reference, confirming the suitability for pulmonal application. In
      conclusion, different IGF-I liquid formulations were studied and compositions
      were identified maintaining bioactivity and chemical stability throughout storage
      at accelerated conditions for up to 4 months as well as compatibility with air
      jet and vibrating-mesh nebulizers.

PMID- 23958319
TI  - Plasma treatment for improving cell biocompatibility of a biodegradable polymer
      scaffold for vascular graft applications.
AB  - Biodegradable synthetic scaffolds are being evaluated by many groups for the
      application of vascular tissue engineering. In addition to the choice of the
      material and the structure of the scaffold, tailoring the surface properties can
      have an important effect on promoting adequate tissue regeneration. The objective
      of this study was to evaluate the effect of an increased hydrophilicity of a
      polycaprolactone vascular graft by treatment with a cold air plasma. To this end,
      treated and untreated scaffolds were characterized, evaluated in vitro with
      smooth muscle cells, and implanted in vivo in the rat model for 3 weeks, both in
      the subcutaneous location and as an aortic replacement. The plasma treatment
      significantly increased the hydrophilicity of the scaffold, with complete wetting
      after a treatment of 60 sec, but did not change fiber morphology or mechanical
      properties. Smooth muscle cells cultured on plasma treated patches adopt a spread
      out morphology compared to a small, rounded morphology on untreated patches.
      Subcutaneous implantation revealed a low foreign body reaction for both types of
      scaffolds and a more extended and dense cellular infiltrate in the plasma treated
      scaffolds. In the vascular position, the plasma treatment induced a better
      cellularization of the graft wall, while it did not affect endothelialization
      rate or intimal hyperplasia. Plasma treatment is therefore an accessible tool to
      easily increase the biocompatibility of a scaffold and accelerate tissue
      regeneration without compromising mechanical strength, which are valuable
      advantages for vascular tissue engineering.

PMID- 23958320
TI  - Design and characterization of core-shell mPEG-PLGA composite microparticles for
      development of cell-scaffold constructs.
AB  - Appropriate scaffolds capable of providing suitable biological and structural
      guidance are of great importance to generate cell-scaffold constructs for cell
      based tissue engineering. The aim of the present study was to develop composite
      microparticles with a structure to provide functionality as a combined drug
      delivery/scaffold system. Composite microparticles were produced by incorporating
      either alginate/dermatan sulfate (Alg/DS) or alginate/chitosan/dermatan sulfate
      (Alg/CS/DS) particles in mPEG-PLGA microparticles using coaxial ultrasonic
      atomization. The encapsulation and distribution of Alg/DS or Alg/CS/DS particles
      in the mPEG-PLGA microparticles were significantly dependent on the operating
      conditions, including the flow rate ratio (Qout/Qin) and the viscosity of the
      polymer solutions (Vout, Vin) between the outer and the inner feeding channels.
      The core-shell composite microparticles containing the Alg/DS particles or the
      Alg/CS/DS particles displayed 40% and 65% DS release in 10 days, respectively, as
      compared to the DS directly loaded microparticles showing 90% DS release during
      the same time interval. The release profiles of DS correlate with the cell
      proliferation of fibroblasts, i.e. more sustainable cell growth was induced by
      the DS released from the core-shell composite microparticles comprising Alg/CS/DS
      particles. After seeding fibroblasts onto the composite microparticles, excellent
      cell adhesion was observed, and a successful assembly of the cell-scaffold
      constructs was induced within 7 days. Therefore, the present study demonstrates a
      novel strategy for fabrication of core-shell composite microparticles comprising
      additional particulate drug carriers in the core, which provides controlled
      delivery of DS and favorable cell biocompatibility; an approach to potentially
      achieve cell-based tissue regeneration.

PMID- 23958321
TI  - Impact of IGF-I release kinetics on bone healing: a preliminary study in sheep.
AB  - Spatiotemporal release of growth factors from a delivery device can profoundly
      affect the efficacy of bone growth induction. Here, we report on a delivery
      platform based on the encapsulation of insulin-like growth factor I (IGF-I) in
      different poly(D,L-lactide) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA)
      microsphere (MS) formulations to control IGF-I release kinetics. In vitro IGF-I
      release profiles generally exhibited an initial burst (14-36% of total IGF-I
      content), which was followed by a more or less pronounced dormant phase with
      little release (2 to 34 days), and finally, a third phase of re-increased IGF-I
      release. The osteoinductive potential of these different IGF-I PL(G)A MS
      formulations was tested in studies using 8-mm metaphyseal drill hole bone defects
      in sheep. Histomorphometric analysis at 3 and 6 weeks after surgery showed that
      new bone formation was improved in the defects locally treated with IGF-I PL(G)A
      MS (n=5) as compared to defects filled with IGF-I-free PL(G)A MS (n=4). The
      extent of new bone formation was affected by the particular release kinetics,
      although a definitive relationship was not evident. Local administration of IGF-I
      resulted in down-regulation of inflammatory marker genes in all IGF-I treated
      defects. The over-expression of growth factor genes in response to IGF-I delivery
      was restricted to formulations that produced osteogenic responses. These
      experiments demonstrate the osteoinductive potential of sustained IGF-I delivery
      and show the importance of delivery kinetics for successful IGF-I-based
      therapies.

PMID- 23958322
TI  - Biocompatibility and osteoconduction of macroporous silk fibroin implants in
      cortical defects in sheep.
AB  - The goal of the presented study was to compare the biocompatibility and cellular
      responses to porous silk fibroin (SF) scaffolds produced in a water-based (UPW)
      or a solvent based process (HFIP) using two different SF sources. For that
      reason, four different SF scaffolds were implanted (n=6) into drill hole defects
      in the cancellous bone of the sheep tibia and humerus. The scaffolds were
      evaluated histologically for biocompatibility, cell-material interaction, and
      cellular ingrowth. New bone formation was observed macroscopically and
      histologically at 8 weeks after implantation. For semiquantitative evaluation,
      the investigated parameters were scored and statistically analyzed (factorial
      ANOVA). All implants showed good biocompatibility as evident by low infiltration
      of inflammatory cells and the absent encapsulation of the scaffolds in connective
      tissue. Multinuclear foreign body giant cells (MFGCs) and macrophages were
      present in all parts of the scaffold at the material surface and actively
      degrading the SF material. Cell ingrowth and vascularization were uniform across
      the scaffold. However, in HFIP scaffolds, local regions of void pores were
      present throughout the scaffold, probably due to the low pore interconnectivity
      in this scaffold type in contrast to UPW scaffolds. The amount of newly formed
      bone was very low in both scaffold types but was more abundant in the periphery
      than in the center of the scaffolds and for HFIP scaffolds mainly restricted to
      single pores.

PMID- 23958324
TI  - Nerve conduit scaffolds for discrete delivery of two neurotrophic factors.
AB  - Axonal repair and regeneration remain critical due to lack of appropriate
      delivery systems for efficient release of neurotrophic factors (NTFs). Recently,
      we have demonstrated the synergistic activity of nerve growth factor (NGF) and
      glial cell line-derived neurotrophic factor (GDNF) on axonal regeneration.
      Combined delivery of GDNF and NGF with individually controlled release kinetics
      may be crucial for exploiting their synergistic action on axonal elongation in
      animals. For engineering discrete NTF release kinetics, we have developed several
      nerve conduits (NCs) using collagen (Col) and silk fibroin (SF); the NC were made
      of Col or SF alone, or of Col and SF layers, or of Col/SF blends, all loaded with
      GDNF and NGF. All NC types provided sustained combined release of NGF and GDNF
      over 28 days. NC made of combinations of Col and SF showed reduced burst and more
      sustained dual release of GDNF and NGF. SF/Col-based NC scaffolds provide an
      adaptable delivery system for growth factors and hold potential for nerve
      regeneration and possibly for other tissue engineering applications.

PMID- 23958323
TI  - Remodeling of tissue-engineered bone structures in vivo.
AB  - Implant design for bone regeneration is expected to be optimized when implant
      structures resemble the anatomical situation of the defect site. We tested the
      validity of this hypothesis by exploring the feasibility of generating different
      in vitro engineered bone-like structures originating from porous silk fibroin
      scaffolds decorated with RGD sequences (SF-RGD), seeded with human mesenchymal
      stem cells (hMSC). Scaffolds with small (106-212 MUm), medium (212-300 MUm), and
      large pore diameter ranges (300-425 MUm) were seeded with hMSC and subsequently
      differentiated in vitro into bone-like tissue resembling initial scaffold
      geometries and featuring bone-like structures. Eight weeks after implantation
      into calvarial defects in mice, the in vitro engineered bone-like tissues had
      remodeled into bone featuring different proportions of woven/lamellar bone
      bridging the defects. Regardless of pore diameter, all implants integrated well,
      vascularization was advanced, and bone marrow ingrowth had started. Ultimately,
      in this defect model, the geometry of the in vitro generated tissue-engineered
      bone structure, trabecular- or plate-like, had no significant impact on the
      healing of the defect, owing to an efficient remodeling of its structure after
      implantation.

PMID- 23958325
TI  - Adipose-derived stem cells combined with neuregulin-1 delivery systems for heart
      tissue engineering.
AB  - Myocardial infarction (MI) is the leading cause of death worldwide, and extensive
      research has therefore been performed to find a cure. Neuregulin-1 (NRG) is a
      growth factor involved in cardiac repair after MI. We previously described how
      biocompatible and biodegradable microparticles, which are able to release NRG in
      a sustained manner, represent a valuable approach to avoid problems related to
      the short half-life after systemic administration of proteins. The effectiveness
      of this strategy could be improved by combining NRG with several cytokines
      involved in cardiac regeneration. The present study investigates the potential
      feasibility of using NRG-releasing particle scaffold combined with adipose
      derived stem cells (ADSC) as a multiple growth factor delivery-based tissue
      engineering strategy for implantation in the infarcted myocardium. NRG-releasing
      particle scaffolds with a suitable size for intramyocardial implantation were
      prepared by TROMS. Next, ADSC were adhered to particle scaffolds and their
      potential for heart administration was assessed in a MI rat model. NRG was
      successfully encapsulated reaching encapsulation efficiencies of 92.58 +/- 3.84%.
      NRG maintained its biological activity after the microencapsulation process.
      ADSCs adhered efficiently to particle scaffolds within a few hours. The ADSC
      cytokine delivery system developed proved to be compatible with intramyocardial
      administration in terms of injectability through a 23-gauge needle and tissue
      response. Interestingly, ADSC-scaffolds were present in the peri-infarted tissue
      2 weeks after implantation. This proof of concept study provides important
      evidence required for future effectiveness studies and for the translation of
      this approach.

PMID- 23958326
TI  - New high throughput screening method for drug release measurements.
AB  - In the field of drug delivery systems, microparticles made of polymeric matrix
      appear as an attractive approach. The in vitro release kinetic profile is crucial
      information when developing new particulate formulations. These data are
      essential for batch to batch comparison, quality control as well as for
      anticipation of in vivo behavior to select the best formulation to go further in
      preclinical investigations. The methods available present common drawbacks such
      as the time- and compound-consumption that does not fit with formulation
      screening requirements in early development stages. In this study, a new
      microscale high throughput screening (HTS) method has been developed to
      investigate drug release kinetic from piroxicam-loaded polylactic acid (PLA) and
      polylactic-co-glycolic acid (PLGA) microparticles. The method is a sample- and
      separation-based method where separation is performed by filtration using 96-well
      micro filter plates. 96 experiments can therefore be performed on one plate in
      one time in a fully automated way and with a very low sample and particle
      consumption. The influence of different parameters controlling release profiles
      was also investigated using this technique. The HTS method gave the same release
      profile than the standard dialysis method. Shaking, particle concentration, and
      the nature of the release medium were found to be of influence. The HTS method
      appears as a reliable method to evaluate drug release from particles with smaller
      standard deviation and less consumption of material. 

PMID- 23958327
TI  - Correlation of hydrotropic solubilization by urea with logD of drug molecules and
      utilization of this effect for topical formulations.
AB  - Solubilization of drugs in aqueous phases of liquid and semisolid environment is
      typically achieved by co-solvents or surfactants. On contrast, solubilization by
      means of hydrotropic agents, i.e., small hydrophilic organic compounds like urea
      or citric acid, is little explored in the context of pharmaceutical formulations.
      Especially, with regard to topical dosage forms, however, hydrotropic
      solubilization can provide valuable alternatives to establish solubilization
      approaches. A difficulty of employing hydrotropic solubilization was that its
      extent could not be predicted for different drug molecules. Using a chemically
      heterogeneous set of 12 compounds relevant for dermatology (with overall 16
      different logD values tested), we were able to demonstrate that hydrotropic
      effects of urea can be predicted by logD values of drugs. All compounds with logD
      values between 2 and 4.5 showed a solubility enhancement factor (EF) of >5 in 40%
      aqueous solutions of urea. For logD values below 2 or above 5, only EF<5 were
      found. For some compounds, e.g., diclofenac (pH 4) and prednicarbate could
      achieved only EF>5 at 5% urea and EF>250 at 20% urea. 

PMID- 23958328
TI  - [Testicular tissue vitrification: evolution or revolution?].
AB  - Preservation of reproductive health is a major concern for patient long-term
      quality of life. While sperm freezing has proven to be effective to preserve
      fertility after puberty, cryopreservation of immature testicular tissue (ITT) is
      emerging as a promising approach for fertility preservation in young boys. Slow
      freezing (SF) is the conventional method used to preserve ITT and has resulted in
      the birth of mice offspring. In humans, methods to preserve ITT are still at the
      research stage. Controlled SF using dimethyl sulfoxide showed preservation of
      proliferative spermatogonia after thawing in a xenotransplantation model used to
      evaluate the efficiency of freezing and thawing procedures. However,
      spermatogonial recovery was low and normal differentiation could not be achieved.
      Both freezing/thawing and the environment of the xenotransplantation model may be
      implicated. Indeed, with SF, ice crystal formation could damage tissue and cells.
      For this reason, vitrification, leading to solidification of a liquid without
      crystallization, may be a promising alternative. ITT vitrification has been
      investigated in different species and shown spermatogonial survival and
      differentiation to the round or elongated spermatids stage. Offspring were also
      recently obtained after vitrification and allotransplantation in avians,
      confirming the potential of vitrification for fertility preservation. In humans,
      vitrification appears to be as efficient as SF in terms of spermatogonial
      survival and initiation of differentiation after xenotransplantation. However,
      before validation of such fertility preservation methods, completion of normal
      spermatogenesis and the fertilization capacity of sperm retrieved from
      cryopreserved and transplanted tissue should be fully investigated. 

PMID- 23958329
TI  - [Use of an in vitro model in bovine to evidence a functional and molecular
      dialogue between preimplantation embryo and oviduct epithelial cells].
AB  - Beyond being a pipe between ovary and uterus, the oviduct is an active player in
      different aspects of early reproductive processes, in particular in the transport
      of embryos to the site of implantation and the regulation of its early
      development. Different studies evidenced a communication between oviduct and
      early embryo at the molecular and functional levels. Since the study of these
      interactions is difficult in vivo, different in vitro systems have been developed
      to mimic the maternal milieu during early development. These systems allowed to
      confirm the action of the cells on the quality of early development (blastocyst
      rate and viability). In turn, the embryos are producing signals that are able to
      modify and adapt the activity of maternal cells. 

PMID- 23958330
TI  - [Being a family today - ethics for assisted reproductive techniques].
AB  - Currently in France, all the children born as a result of an assisted
      reproduction procedure, represent 2.5% of all births. Although this proportion is
      not high, it is not to be neglected, particularly with regard to the sociological
      issues raised by assisted reproduction technologies (ART) - i.e. removing
      anonymity of gamete donation, post mortem insemination, ART access to single
      women and gay couples, surrogacy - to name four of the most prominent debates.
      What is new with ART is that a new therapeutic target of medicine is being
      developed, in other words procreation. Now it is no longer necessary for a man
      and a woman to resort to sex to have a child. This is a profound questioning of
      the representation of what appeared to be intangible, with some sort of divine
      aura. How, in this context, developing an ethics for ART? From a fethnographic
      field survey, we show here how this ethos of ART develops and how, therefore, we
      consider the multiple ways of being a family today. 

PMID- 23958331
TI  - Quantifying (12/13)CH(4) migration and fate following sub-surface release to an
      agricultural soil.
AB  - Following gas generation in a Geological Disposal Facility (GDF), (14)C
      containing gases could migrate through the geosphere, eventually diffusing into
      soils at the Earth's surface. This paper reports summary results from laboratory
      and field experiments to obtain information on the probable rates of a) diffusive
      transport and b) oxidation of (12/13)CH(4) (as a surrogate for (14)CH4) in a
      typical agricultural soil in the UK. Rates of CH(4) oxidation were generally low
      in the field and undisturbed soil columns, though a re-packed column of
      homogenised topsoil oxidised ambient atmospheric CH(4) 20* faster than an
      undisturbed soil column. In contrast to low observed rates of CH(4) oxidation,
      the effective diffusion of CH(4) through the soil was rapid. Isotopically
      labelled CH(4) injected at a depth of 45 cm in the field diffused to the surface
      and exited the soil over a time period ranging from 8 to 24 h. The rate of CH(4)
      diffusion through the soil was increased by the presence of ryegrass roots which
      increased soil porosity and decreased water content. delta(13)C values for
      laboratory column soils after labelled CH(4) injection experiments showed no sign
      of residual (13)C, despite the extremely high delta(13)C values of the injected
      (12/13)CH(4). If laboratory observations are confirmed by measurements in field
      samples it can be concluded that the majority of (14)CH(4) from a GDF which
      enters a soil with low methanotrophic activity will be lost to the free
      atmosphere after diffusing rapidly through the soil column.

PMID- 23958332
TI  - Pilot study of a social network intervention for heroin users in opiate
      substitution treatment: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Research indicates that 3% of people receiving opiate substitution
      treatment (OST) in the UK manage to achieve abstinence from all prescribed and
      illicit drugs within 3 years of commencing treatment, and there is concern that
      treatment services have become skilled at engaging people but not at helping them
      to enter a stage of recovery and drug abstinence. The National Treatment Agency
      for Substance Misuse recommends the involvement of families and wider social
      networks in supporting drug users' psychological treatment, and this pilot
      randomized controlled trial aims to evaluate the impact of a social network
      focused intervention for patients receiving OST. METHODS AND DESIGN: In this two
      site, early phase, randomized controlled trial, a total of 120 patients receiving
      OST will be recruited and randomized to receive one of three treatments: 1) Brief
      Social Behavior and Network Therapy (B-SBNT), 2) Personal Goal Setting (PGS) or
      3) treatment as usual. Randomization will take place following baseline
      assessment. Participants allocated to receive B-SBNT or PGS will continue to
      receive the same treatment that is routinely provided by drug treatment services,
      plus four additional sessions of either intervention. Outcomes will be assessed
      at baseline, 3 and 12 months. The primary outcome will be assessment of illicit
      heroin use, measured by both urinary analysis and self-report. Secondary outcomes
      involve assessment of dependence, psychological symptoms, social satisfaction,
      motivation to change, quality of life and therapeutic engagement. Family members
      (n = 120) of patients involved in the trial will also be assessed to measure the
      level of symptoms, coping and the impact of the addiction problem on the family
      member at baseline, 3 and 12 months. DISCUSSION: This study will provide
      experimental data regarding the feasibility and efficacy of implementing a social
      network intervention within routine drug treatment services in the UK National
      Health Service. The study will explore the impact of the intervention on both
      patients receiving drug treatment and their family members. TRIAL REGISTRATION: 
      TRIAL REGISTRATION NUMBER: ISRCTN22608399. ISRCTN22608399 registration:
      27/04/2012. Date of first randomisation: 14/08/2012.

PMID- 23958333
TI  - Mortality in eating disorders: a follow-up study of adult eating disorder
      patients treated in tertiary care, 1995-2010.
AB  - Elevated mortality risk in anorexia nervosa has been established, but less is
      known about the outcomes of bulimia nervosa and binge eating disorder. In this
      follow-up study we determined mortality in adults (N=2450, 95% women) admitted to
      the eating disorder clinic of the Helsinki University Central Hospital in the
      period 1995-2010. Most of the patients (80.7%) were outpatients. For each patient
      four controls were selected and matched for age, sex and place of residence. The
      matching was taken into account by modelling end-point events using Cox's
      proportional hazard model. The hazard ratio (HR) for all-cause mortality was 6.51
      (95% CI 3.46-12.26) in broad anorexia nervosa (AN), 2.97 (95% CI 1.90-4.65) in
      broad bulimia nervosa (BN), and 1.77 (95% CI 0.60-5.27) in binge eating disorder
      (BED). Mortality risk in broad AN was highest during the first years after
      admission but declined thereafter, while in broad BN the mortality risk started
      to rise two years after the first admission. The HR for suicide was elevated both
      in broad AN (HR 5.07; 95% CI 1.37-18.84) and in broad BN (HR 6.07; 95% CI 2.47
      14.89). Results show that eating disorders are associated with increased
      mortality risk even when specialised treatment is available. 

PMID- 23958334
TI  - Temperament and character in transsexuals.
AB  - The aim of this study was to evaluate personality in transsexuals. The
      Temperament and Character Inventory (TCI) profiles of 166 male-to-female (MF) and
      88 female-to-male (FM) transsexuals were compared with those of a control group
      of males and females. MF and FM transsexuals scored significantly lower than
      males and females in RD4 (more independent) and C3 (more self-centeredness). MF
      transsexuals scored higher than males and females in HA4 (more fatigable), ST and
      ST3 (more spiritual acceptance), and lower in C5 (more opportunistic); moreover,
      they showed higher scores than males in RD1 (more sentimental) and lower than
      females in C (less cooperativeness). FM transsexuals scored lower than females in
      HA2 (more daring and confident), RD (less sentimental), and C5 (more
      opportunistic). Compared with FM, MF transsexuals scored higher on HA2 (more
      fearful), RD, RD1 (more sentimental), ST, ST2 and ST3 (more spiritual). All these
      differences were less than half a standard deviation except for C3. Data show
      that transsexuals and controls display a similar personality profile, even though
      there are some differential personality traits. Moreover, the personality profile
      of transsexuals was closer to the profile of subjects who shared their gender
      identity than those who shared their anatomical sex. 

PMID- 23958335
TI  - Can a theory-based educational intervention change nurses' knowledge and
      attitudes concerning cancer pain management? A quasi-experimental design.
AB  - BACKGROUND: Registered Nurses (RNs) play an important role in caring for patients
      suffering from cancer pain. A lack of knowledge regarding pain management and the
      RNs' own perception of cancer pain could act as barriers to effective pain
      management. Educational interventions that target RNs' knowledge and attitudes
      have proved promising. However, an intervention consisting of evidence-based
      practice is a multifaceted process and demands behavioural and cognitive changes
      to sustain the effects of the intervention. Therefore, our study aimed to
      investigate if a theory-based educational intervention could change RNs'
      knowledge and attitudes to cancer pain and pain management, both four and 12
      weeks after the start of the intervention. METHODS: A quasi-experimental design
      with non-equivalent control groups was used. The primary outcome was measured
      using a modified version of the instrument Nurses' Knowledge and Attitudes Survey
      Regarding Pain (NKAS) at baseline, four weeks and 12 weeks after the start of the
      intervention to evaluate its persistence. The intervention's educational
      curriculum was based on the principles of Ajzen's Theory of Planned Behaviour and
      consisted of interactive learning activities conducted in workshops founded on
      evidence-based knowledge. The RN's own experiences from cancer pain management
      were used in the learning process. RESULTS: The theory-based educational
      intervention aimed at changing RNs knowledge and attitudes regarding cancer pain
      management measured by primary outcome NKAS resulted in a statistical significant
      (p<0.05) improvement of total mean score from baseline to four weeks at the
      intervention ward. CONCLUSIONS: The findings of this study, suggest that a theory
      based educational intervention focused at RNs can be effective in changing RN's
      knowledge and attitudes regarding cancer pain management. However, the high
      number of dropouts between baseline and four weeks needs to be taken into account
      when evaluating our findings. Finally, this kind of theory-based educational
      intervention with interactive learning activities has been sparsely researched
      and needs to be evaluated further in larger projects. TRIAL REGISTRATION:
      Clinical Trials. Gov: NCT01313234.

PMID- 23958336
TI  - Enhanced levels of asymmetric dimethylarginine in a serum of middle age patients
      with myelodysplastic syndrome.
AB  - Myelodysplastic syndromes (MDS) are hematological malignancies of unclear
      etiology where oxidative stress may contribute to the pathogenesis.
      Methylarginines, naturally occurring inhibitors of NO synthase, can increase
      superoxide generation from uncoupled NO synthase. We found significant increase
      in concentrations of asymmetric dimethylarginine (0.84 +/- 0.32 MUmol/L, p =
      0.0022) and malondialdehyde (0.77 +/- 0.11 MUmol/L, p < 0.001) in sera of MDS
      patients vs controls (asymmetric dimethylarginine: 0.56 +/- 0.16 MUmol/L,
      malondialdehyde: 0.52 +/- 0.07 MUmol/L). On the contrary, nitrites concentrations
      were significantly decreased in MDS patients (1.71 +/- 0.46 MUmol/L, p = 0.0028)
      vs controls (2.16 +/- 0.38 MUmol/L). We suppose that the oxidative stress in MDS
      is enhanced due to methylated arginines influence on NO synthase activity
      impairment.

PMID- 23958337
TI  - Sports drink consumption and diet of children involved in organized sport.
AB  - BACKGROUND: Organized sport provides one option for children to be physically
      active. However, there is a paucity of information about the relationship between
      children's participation in organized sport and their diet, and specifically
      their sports drink consumption. Therefore, the relationship between sports
      participation in children and the consumption of sports drinks, sugar-sweetened
      beverages (SSBs) and other components of diet was examined. METHODS: A cross
      sectional descriptive study was conducted using baseline data from the Action
      Schools! BC Dissemination study cohort (n = 1421; 9.90 (0.58) y; 736 girls, 685
      boys). The differences between the dietary behaviours of children participating
      in organized sport (sport) versus those that did not participate (non-sport) was
      examined. A modified Physical Activity Questionnaire for Older Children (PAQ-C)
      was used to measure physical activity levels and participation in organized
      sport. A Food Frequency Questionnaire (FFQ) and 24-hour dietary recall were used
      to assess eating behaviour and macronutrient intake (including protein, fat, and
      carbohydrate as well as sugar, fibre and total calories). Fruit, vegetable and
      beverage quantities were hand-tallied from the dietary recall. Fruit, vegetable
      and beverage frequency was assessed using the FFQ. Analysis of covariance
      (ANCOVA) was used to analyse differences between groups and a chi-square test of
      association was use to determine if participation in sport was significantly
      associated with the proportion of children consuming sports drinks and SSBs, and
      with gender. RESULTS: Children involved in sport had a lower body mass index
      (BMI) and were more physically active than children in the non-sport group (p <
      0.01). Only a small number (n = 20/1421) of children consumed sports drinks and
      no difference in consumption of sports drink between sport and non-sport
      participants (p > .05) was observed. However, children involved in organized
      sport consumed more total calories, fat, fibre, fruit, vegetables and non
      flavoured milk (p < 0.01) than non-sport children. CONCLUSIONS: Children involved
      in organized sport were more physically active, consumed a healthier diet than
      non-participants and on average had lower BMI's despite consuming more calories.
      As consumption of sports drinks among this age group was low, this may be an
      ideal time to begin educating children and their parents about the appropriate
      consumption of sports drinks and the perils of consuming too many SSBs,
      specifically.

PMID- 23958338
TI  - Life cycle environmental impacts of a prospective palm-based biorefinery in Para
      State-Brazil.
AB  - The availability of about 18 million hectares of grassland in Para State, Brazil,
      and the possibility of increasing the livestock density display a good
      perspective for the oil palm expansion in pasture land. A life cycle assessment
      is performed for a prospective palm-based biorefinery to view two regional and
      one global environmental impact and the consequences of the land-use change in
      terms of GHG emissions. Oil palm cultivation in an area of ~110,000 hectares of
      land can annually produce ~39,000 tons of bioethanol, ~340,000 tons of biodiesel,
      ~268 GW h net electricity and other co-products. The life cycle GHG emissions
      reduction for biodiesel and bioethanol as compared to fossil diesel and gasoline
      would be 76.9-79.3% and 83.7-88.6%. The advantage of grassland rehabilitation by
      oil palm plantation is the removal of ~188 t CO2/ha from the atmosphere during
      the plant lifetime. The entire inflows and outflows for the conversion processes
      are schemed.

PMID- 23958339
TI  - Elucidating acetogenic H2 consumption in dark fermentation using flux balance
      analysis.
AB  - In this study, a flux balance analysis (FBA) was adopted to estimate the activity
      of acetogenic H2-consuming reaction. Experimental data at different substrate
      concentrations of 10, 20, and 30 g COD/L showing the lowest, medium, and highest
      H2 yields, respectively, were used in the FBA to calculate the fluxes. It was
      interesting to note that the hydrogenase activity based on R12 (2Fd(+)+2H(+)
      >2Fd(2+)+H2, ferredoxin (Fd)) flux was most active at 10 g COD/L. The flux of R17
      (4H2+2CO2->CH3COOH), a mechanism for reutilizing produced H2, increased in steps
      of 0.030, 0.119, and 0.467 as the substrate concentration decreased.
      Contradictory to our general understanding, acetate production found to have a
      negligible or even negative effect on the final H2 yield in dark fermentation.

PMID- 23958340
TI  - Counterpoint: Is there a need for supplemental XRT in intermediate-risk prostate
      cancer patients?

PMID- 23958341
TI  - Interstitial pulsed-dose-rate brachytherapy for head and neck cancer--Single
      institution long-term results of 385 patients.
AB  - PURPOSE: To assess the long-term results of protocol-based pulsed-dose-rate (PDR)
      interstitial brachytherapy (iBT) in 385 patients with head and neck cancer who
      underwent PDR-iBT preferably after minimal, nonmutilating surgery. METHODS AND
      MATERIALS: From 1997 to 2009, a total of 385 patients received protocol-based PDR
      iBT for head and neck cancer. Brachytherapy was preceded by surgery in most of
      our patients (326/385, 84.7%). Altogether, 246 of 385 patients (63.9%) received
      iBT alone and 135 of 385 patients (36.1%) in combination with external beam
      radiation therapy. The analysis was done after a median followup of 63 months.
      RESULTS: The 5-, 10-, and 15-year local relapse-free survival rates according to
      Kaplan-Meier test for all analyzed patients were 85.8%, 83.1%, and 80.2%,
      respectively. The 5-, 10-, and 15-year overall survival and disease-free survival
      rates were 68.9%, 52.2%, and 44.1%, and 81.3%, 79.3%, and 76.3%, respectively.
      For N0-/N1- vs. N2-patients, we observed significantly different 5-year local
      recurrence-free survival rates with values of 92.3% and 73.7%, respectively
      (p=0.007). No other patient or treatment-related parameters had a significant
      influence on treatment results. Serious late side effects, such as soft tissue or
      bone necrosis, were observed in 39 of 385 patients (10.2%) and 18 of 385 patients
      (4.9%), respectively. CONCLUSIONS: The PDR-iBT with 0.4-0.7Gy each hour, 24h per
      day for patients with head and neck cancer is a proven, effective, and safe
      treatment method with excellent long-term data.

PMID- 23958342
TI  - Positive words or negative words: whose valence strength are we more sensitive
      to?
AB  - The present study investigates the human brains' sensitivity to the valence
      strength of emotionally positive and negative chinese words. Event-Related
      Potentials were recorded, in two different experimental sessions, for Highly
      Positive (HP), Mildly Positive (MP) and neutral (NP) words and for Highly
      Negative (HN), Mildly Negative (MN) and neutral (NN) words, while subjects were
      required to count the number of words, irrespective of word meanings. The results
      showed a significant emotion effect in brain potentials for both HP and MP words,
      and the emotion effect occurred faster for HP words than MP words: HP words
      elicited more negative deflections than NP words in N2 (250-350 ms) and P3 (350
      500 ms) amplitudes, while MP words elicited a significant emotion effect in P3,
      but not in N2, amplitudes. By contrast, HN words elicited larger amplitudes than
      NN words in N2 but not in P3 amplitudes, whereas MN words produced no significant
      emotion effect across N2 and P3 components. Moreover, the size of emotion-neutral
      differences in P3 amplitudes was significantly larger for MP compared to MN
      words. Thus, the human brain is reactive to both highly and mildly positive
      words, and this reactivity increased with the positive valence strength of the
      words. Conversely, the brain is less reactive to the valence of negative relative
      to positive words. These results suggest that human brains are equipped with
      increased sensitivity to the valence strength of positive compared to negative
      words, a type of emotional stimuli that are well known for reduced arousal.

PMID- 23958343
TI  - Novel effects of edaravone on human brain microvascular endothelial cells
      revealed by a proteomic approach.
AB  - Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a free radical scavenger used
      for acute ischemic stroke. However, it is not known whether edaravone works only
      as a free radical scavenger or possess other pharmacological actions. Therefore,
      we elucidated the effects of edaravone on human brain microvascular endothelial
      cells (HBMECs) by 2 dimensional fluorescence difference gel electrophoresis (2D
      DIGE). We found 38 protein spots the intensity of which was significantly altered
      1.3 fold on average (p< 0.05) by the edaravone treatment and successfully
      identified 17 proteins of those. Four of those 17 proteins were cytoskeleton
      proteins or cytoskeleton-regulating proteins. Therefore, we subsequently
      investigated the change of size and shape of the cells, the actin network, and
      the tight junction of HBMEC by immunocytochemistry. As a result, most edaravone
      treated HBMECs became larger and rounder compared with those that were not
      treated. Furthermore, edaravone-treated HBMECs formed gathering zona occludens
      (ZO)-1, a tight junction protein, along the junction of the cells. In addition,
      we found that edaravone suppressed interleukin (IL)-1beta-induced secretion of
      monocyte chemoattractant protein-1 (MCP-1), which was reported to increase cell
      permeability. We found a novel function of edaravone is the promotion of tight
      junction formations of vascular endothelial cells partly via the down-regulation
      of MCP-1 secretion. These data provide fundamental and useful information in the
      clinical use of edaravone in patients with cerebral vascular diseases. 

PMID- 23958344
TI  - Spinal cord injury induced changes of nuclear receptors PPARalpha and LXRbeta and
      modulation with oleic acid/albumin treatment.
AB  - In previous studies with animal models of spinal cord injury (SCI)
      pharmacological activation of peroxisome proliferator activated receptors (PPAR)
      and liver X receptors (LXR) were used to reduce tissue damage and promote
      behavioral recovery in animal models. We have studied the endogenous expression
      of the transcription factors PPARalpha and LXRbeta in the chronic stage after SCI
      in rats. The immunohistochemical investigation revealed a long lasting increase
      in the level of PPARalpha in white matter in the vicinity of the lesion site. The
      source of this signal was identified in a subpopulation of astrocytes outside of
      the glial scar area. Intrathecal injections of oleic acid/albumin reduced the
      lesion-induced PPARalpha immunoreactivity. In addition, ependymal cells displayed
      a prominent PPARalpha signal in the non-injured spinal cord, and continued to
      express the receptor as they proliferated and migrated within the damaged tissue.
      The nuclear receptor LXRbeta was detected at similar levels after SCI as in sham
      operated animals. We found high levels of immunoreactivity in the gray matter,
      while in the white matter it was present in subpopulations of astrocytes and
      oligodendrocytes. Macrophages that had accumulated within the center of the
      lesion contained LXRbeta in their cell nuclei. Possible endogenous functions of
      PPARalpha and LXRbeta after SCI are discussed, specifically the control of fatty
      acid and cholesterol metabolism and the regulation of inflammatory reactions. 

PMID- 23958345
TI  - Antioxidant lignoids from leaves of Ribes nigrum.
AB  - Phytochemical investigation of the leaves of Ribes nigrum resulted in the
      isolation of fourteen compounds, including four 7,7'-epoxylignans, three
      tetrahydrofuran-type sesquilignans, and a spirocyclic dilignan. Their structures
      were elucidated by extensive spectroscopic analyses and by chemical
      transformations. The isolated compounds were evaluated for their antioxidant
      activities using superoxide anion scavenging assay and DPPH free radical
      scavenging assay. Ribesin D and ribesin G showed the most potent superoxide anion
      scavenging activity with EC50 values of 1.24 and 1.12 MUM, respectively, and the
      structure-activity relationship was discussed.

PMID- 23958346
TI  - [The clinic of apathy in schizophrenia: a critical review of the issue].
AB  - INTRODUCTION: Today the concept of apathy is subject to many questions. This
      psychological state is present and predominant in different disorders such as
      neurodegenerative and psychiatric diseases or neurological acquired disorders.
      Apathy is a part of the clinical vocabulary, however, we can note that in the
      literature there remains confusion in its definition, and we can find an amalgam
      with other clinical symptoms. OBJECTIVES: The aim of this review is to provide a
      clarification of the concept of apathy in clinical practice in schizophrenia as
      well as to highlight the gaps that exist. LITERATURE FINDINGS: Apathy belongs to
      the negative symptoms of schizophrenia. For its understanding, it is necessary to
      define apathy as a multidimensional syndrome (cognitive, emotional, and
      behavioral) manifesting as a quantitative reduction of voluntary behaviors
      directed toward one or several goals. However, at present, we are witnessing a
      reductionist and simplistic conception of the syndrome of apathy and this
      especially in the Anglo-Saxon literature. Several authors reduce apathy to its
      behavioral component, so in other words, to avolition/amotivation. Avolition
      refers to a loss of self-initiated and spontaneous behaviors. In this definition
      only observable behavior is taken into account and not the underlying mechanisms
      (cognitive and emotional). In order to understand the syndrome of apathy, it is
      necessary to have a holistic and multidimensional outlook. Some authors have
      proposed diagnostic criteria for apathy by taking into account the different
      dimensions of apathy. Moreover not only is apathy confused with avolition, but it
      is also still difficult to distinguish it from depression. Apathy and depression
      share common clinical signs (i.e. loss of interest), but they also have distinct
      clinical signs (lack of motivation for apathy, and suicidal ideation for
      depression). Authors have shown that the presence of one symptom (apathy or
      depression) does not predict the presence of the other. An apathetic patient does
      not have to be necessarily in a depressive state and vice versa. However, to our
      knowledge, there is no data capable of distinguishing depression from apathy in
      schizophrenia, and knowing what is the part of one and the other when the patient
      has both symptoms. In addition, we can see that the confusion that persists
      between those two symptoms also stems from assessment tools. Indeed, some
      assessment tools such as the Montgomery and Asberg Depression Rating Scale
      (MARDS) have an apathy subscale. Therefore, this scale does not only evaluate
      depression. Regarding the assessment of apathy in schizophrenia, there are
      specific and nonspecific tools. Nonspecific tools define apathy differently. For
      this reason, authors have proposed to measure apathy by using analytic factors of
      negative symptoms. In this case, apathy is going to be assessed by the factor
      "motivation/pleasure" including anhedonia, asociality and avolition. This factor
      will provide the possibility of a better assessment of apathy. Concerning
      specific scales (like AES), there are gaps such as a lack of standardization in
      the execution and the quotation. Furthermore, no scale takes into account the
      factors causing apathy. CONCLUSION: Knowing the reasons for apathy is necessary
      because this syndrome is frequent in schizophrenia, and it is found in the
      different phases of this disease (prodromal, first episode psychosis, and
      chronic). In addition, apathy has significant functional consequences on the
      patient's quality of life, as well as on his or her global functioning. Indeed,
      apathy impacts on his or her social and professional life. Patients with
      schizophrenia have a loss of autonomy, less employment and social withdrawal.
      Consequently, interest in its drug or treatment it is obvious. However, drug and
      non-drug treatments are not specific to apathy and therefore little effective on
      this syndrome. Implications to stimulate future research are presented.

PMID- 23958347
TI  - High fat diet induces hypermethylation of the hypothalamic Pomc promoter and
      obesity in post-weaning rats.
AB  - Impaired response of the brain to the leptin signal leads to a persisting
      dysregulation of food intake and energy balance. High plasma leptin or insulin
      should activate proopiomelanocortin (POMC), the precursor of the anorexigenic
      neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) in the hypothalamic
      arcuate nucleus (ARC). Nevertheless, in obesity, this signal transduction pathway
      might be impaired. In this study we investigated whether chronic high fat (HF)
      diet consumption from post-weaning to adulthood increases CpG methylation of the
      Pomc promoter. The hypothesis that this would disrupt the essential binding of
      the transcription factor Sp1 to the Pomc promoter was tested. Male rats were
      raised from postnatal day 21 till 90 on either HF or standard diet. As a result
      HF fed rats were significantly heavier, with high leptin and insulin levels in
      their plasma but almost no changes in ARC mRNA expression levels of Pomc. The
      Pomc promoter area in the HF-treated rats was found to be hypermethylated.
      Furthermore, there was a direct correlation in individual rats between CpG
      methylation at specific sites that affect Sp1 binding and plasma leptin levels
      and/or body weight. Although, as expected the HF diet resulted in up-regulation
      of Sp1, the binding of Sp1 to the hypermethylated Pomc promoter was significantly
      reduced. Therefore, we suggest that hypermethylation on the promoter region of
      the Pomc gene can emerge at post-lactation periods and interfere with
      transcription factor binding, thus blocking the effects of high leptin levels,
      leading to obesity. 

PMID- 23958348
TI  - Experimental biomechanical study of the primary stability of different
      osteosynthesis systems for mandibular reconstruction with an iliac crest graft.
AB  - We did biomechanical loading tests to compare the quantity and quality of
      interfragmentary movement in fractured human cadaver mandibles that had been
      reconstructed with iliac crest using 3 different osteosynthesis systems. Eighteen
      mandibles from human cadavers with a 4.5 cm paramedian L-type defect were
      reconstructed with bone from the iliac crest using 3 different osteosynthesis
      systems and continuously loaded on the "Mandibulator" test bench. Six mandibles
      each had the bones joined together using 2 monocortical non-locking plates, 2
      monocortical locking plates, or a single bicortical locking plate/fracture gap.
      Macroscopic deformation, failure mechanisms, and movement of the fracture gap in
      all 3 dimensions were assessed and quantified over increasing loading by
      PONTOS((r)) optical measurement systems. Final mechanisms of failure were
      excessive deformation of the plate, fracture of the mandibular fragments, and
      failure of the iliac crest graft. The plate became deformed mainly in the
      miniplate group. The iliac crest graft failed in all the specimens in which
      osteosynthesis was performed by a 6-hole TriLock((r)) plate. Interfragmentary
      movement was minimised in the miniplate group. All three osteosynthesis systems
      provided sufficient stability for reconstruction when mechanically loaded up to
      100 N. The miniplate allowed less movement in the gap and gave better stability
      than the two TriLock((r)) plate systems. The superiority of the miniplate was
      significant when compared with the 4-hole TriLock((r)) plate. The transplant
      failed mainly in the 6-hole TriLock((r)) group, which suggests that the iliac
      crest graft works better with the miniplate as a more malleable osteosynthesis
      system.

PMID- 23958349
TI  - Towards virtual surgery in oral cancer to predict postoperative oral functions
      preoperatively.
AB  - Our aim was to develop a dynamic virtual model of the oral cavity and oropharynx
      so that we could incorporate patient-specific factors into the prediction of
      functional loss after advanced resections for oral cancer. After a virtual
      resection, functional consequences can be assessed, and a more substantiated
      decision about treatment can be made. In this study we used a finite element
      model of the tongue, which can be implemented in the total virtual environment in
      the future. We analysed the movements and changes in volume, and the effects of
      changes in the material variables, to mimic scar tissue. The observed movements
      were in accordance with descriptions of in vivo movements. Affected movements
      caused by the mimicked scar tissue were also similar to expectations. Some
      changes in volume were measured, particularly in individual elements. We have
      taken the first steps in the development of a finite element model of the tongue.
      Now, refinement is necessary to make the model suitable for future use in virtual
      surgery. 

PMID- 23958350
TI  - Late intracranial haemorrhage and subsequent carotid-cavernous sinus fistula
      after fracture of the facial bones.
AB  - Carotid-cavernous sinus fistula is an arteriovenous fistula between the internal
      carotid artery and the cavernous sinus, and is usually caused by a traumatic tear
      or a ruptured aneurysm of the cavernous segment of the internal carotid artery.
      We describe a rare case of delayed intracranial haemorrhage and carotid-cavernous
      sinus fistula that presented 3 weeks after fracture of the facial bones. The
      patient developed orbital apex syndrome including ptosis of upper eyelid,
      pulsatile exophthalmos, chemosis, loss of ocular motility, monocular blindness on
      the right, and numbness of the right infraorbital region. After transcatheter
      intra-arterial embolisation, the ptosis and chemosis improved. 

PMID- 23958351
TI  - Dexmedetomidine decreases the oral mucosal blood flow.
AB  - There is an abundance of blood vessels in the oral cavity, and intraoperative
      bleeding can disrupt operations. There have been some interesting reports about
      constriction of vessels in the oral cavity, one of which reported that gingival
      blood flow in cats is controlled by sympathetic alpha-adrenergic fibres that are
      involved with vasoconstriction. Dexmedetomidine is a sedative and analgesic agent
      that acts through the alpha-2 adrenoceptor, and is expected to have a
      vasoconstrictive action in the oral cavity. We have focused on the relation
      between the effects of alpha-adrenoceptors by dexmedetomidine and
      vasoconstriction in oral tissues, and assessed the oral mucosal blood flow during
      sedation with dexmedetomidine. The subjects comprised 13 healthy male volunteers,
      sedated with dexmedetomidine in a loading dose of 6 MUg/kg/h for 10 min and a
      continuous infusion of 0.7 MUg/kg/h for 32 min. The mean arterial pressure (MAP),
      heart rate (HR), cardiac output (CO), stroke volume (SV), systemic vascular
      resistance (SVR), and palatal mucosal blood flow (PMBF) were measured at 0, 5,
      10, 12, 22, and 32 min after the start of the infusion. The HR, CO, and PBMF
      decreased significantly during the infusion even though there were no differences
      in the SV. The SVR increased significantly but the PMBF decreased significantly.
      In conclusion, PMBF was reduced by the mediating effect of dexmedetomidine on
      alpha-2 adrenoceptors.

PMID- 23958352
TI  - Identification of genuine primary pulmonary NK cell lymphoma via
      clinicopathologic observation and clonality assay.
AB  - Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is an uncommon
      lymphoma associated with the Epstein-Barr virus (EBV). It most commonly involves
      the nasal cavity and upper respiratory tract. Primary pulmonary NK/T cell
      lymphoma is extremely rare. If a patient with a NK or T-cell tumor has an unusual
      reaction to treatment or an unusual prognosis, it is wise to differentiate NK
      from T-cell tumors. The clinicopathologic characteristics, immunophenotype, EBV
      in situ hybridization, and T cell receptor (TCR) gene rearrangement of primary
      pulmonary NK cell lymphoma from a 73-year-old Chinese woman were investigated and
      the clonal status was determined using female X-chromosomal inactivation
      mosaicism and polymorphisms at the phosphoglycerate kinase (PGK) gene. The lesion
      showed the typical histopathologic characteristics and immunohistochemical
      features of NK/T cell lymphoma. However, the sample was negative for TCR gene
      rearrangement. A clonality assay demonstrated that the lesion was monoclonal. It
      is concluded that this is the first recorded case of genuine primary pulmonary NK
      cell lymphoma. The purpose of the present work is to recommend that pathologists
      carefully investigate the whole lesion to reduce the likelihood that primary
      pulmonary NK cell lymphoma will be misdiagnosed as an infectious lesion. In
      addition, TCR gene rearrangement and clonal analysis, which is based on female X
      chromosomal inactivation mosaicism and polymorphisms at PGK and androgen receptor
      (AR) loci, were found to play important roles in differentiating NK cell lymphoma
      from T cell lymphoma. VIRTUAL SLIDES: The virtual slide(s) for this article can
      be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5205300349457729.

PMID- 23958354
TI  - One-step simple sonochemical fabrication and photocatalytic properties of Cu2O
      rGO composites.
AB  - An easy, one-step synthesis of Cu2O-reduced graphene composites (Cu2O-rGO) was
      developed using a simple sonochemical route without any surfactants or templates.
      The morphology and structure of the Cu2O-rGO composites were characterised using
      techniques such as scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR)
      spectroscopy, Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). The
      results indicated that the Cu2O sphere is approximately 200 nm in diameter and
      composed of small Cu2O particles approximately 20 nm in diameter. The morphology
      and composition of the Cu2O-rGO composites could be well controlled by simply
      changing the mole ratio of the reactants under ultrasonic irradiation. The Cu2O
      rGO composites displayed better photocatalytic performance for the degradation of
      methyl orange (MO) than pure Cu2O spheres, which may have potential applications
      in water treatment, sensors, and energy storage.

PMID- 23958353
TI  - Cerebellar degeneration associated with mGluR1 autoantibodies as a paraneoplastic
      manifestation of prostate adenocarcinoma.
AB  - Subacute cerebellar degeneration associated with metabotropic glutamate receptor
      type 1 (mGluR1) autoantibodies is an uncommon syndrome known to be part of the
      spectrum of paraneoplastic cerebellar degenerations associated with neuronal
      autoantibodies. We describe a patient with prostate adenocarcinoma who developed
      a subacute cerebellar ataxia. Autoantibodies specific to mGluR1 were detected in
      patient's serum and cerebrospinal fluid (CSF). Immunohistochemistry analyses of
      patient's prostate adenocarcinoma revealed abundant mGluR1 expression in luminal
      acinar epithelial cells and binding of patient's IgGs to tumoral mGluR1. These
      findings suggest that cerebellar degeneration associated with mGluR1 antibodies
      can be a paraneoplastic accompaniment of prostate adenocarcinoma. 

PMID- 23958355
TI  - Parametric study of acoustically-driven microbubble cavitations in a sonochemical
      reactor.
AB  - The bubble cavitation along a solid wall is investigated with a three-dimensional
      model based on the indirect boundary element method. Kinetic energy and Kelvin
      impulse are calculated in order to quantify the strength of cavitation. The
      influences of acoustic wave amplitude and frequency and liquid properties on the
      strength of cavitation are investigated. This study was carried out in order to
      better understand the relation between microscale processes and macroscale
      parameters in a sonochemical reactor used for impregnation of fabrics with
      nanoparticles. 

PMID- 23958356
TI  - Ultrasound-promoted green approach for the synthesis of sulfonamides using
      natural, stable and reusable Natrolite nanozeolite catalyst at room temperature.
AB  - Natural Natrolite nanozeolite has been investigated as an efficient and reusable
      catalyst for the N-sulfonylation of amines under ultrasound irradiation at room
      temperature. Compared with traditional methods, the significant advantages for
      method are green solvent, milder and cleaner conditions, higher purity and
      yields, shorter reaction time, easier work-up procedure and the lower generation
      of waste or pollutions. The catalyst can be recovered and reused several times
      without significant loss of its catalytic activity. 

PMID- 23958357
TI  - Fabrication and sonocatalytic property of AgPO3 microsphere.
AB  - AgPO3 microspheres were prepared by a simple hydrothermal method. The AgPO3
      microspheres were characterized by X-ray powder diffraction (XRD), scanning
      electronic microscopy (SEM), Brunauer-Emmett-Teller (BET), UV-vis absorption
      spectroscopy (UV-vis), and photoluminescence (PL) measurement. SEM reveals that
      the AgPO3 microspheres were constructed by the accumulation of small particles.
      The as-prepared AgPO3 microspheres sonocatalytically degraded Rhodamine B (RhB)
      excellently under ultrasonic irradiation. The sonocatalytic ability results from
      the OH radicals induced by AgPO3 microspheres under ultrasonic irradiation. The
      effects of other conditions on ultrasonic activity were also investigated. The
      content of OH radicals in the reaction system was determined to further verify
      the above conclusions. 

PMID- 23958358
TI  - Sexually transmitted diseases.
AB  - Sexually transmitted infections (STIs), also referred to as sexually transmitted
      diseases, remain a growing worldwide problem and public health issue. This
      article covers the epidemiology of STIs, the history and physical findings,
      screening guidelines, and the general plan to combat STIs. Prevention is
      discussed using the latest information from the Centers for Disease Control and
      Prevention and other references. Infections discussed from the standpoint of
      cause, epidemiology, risk factors, clinical disease, diagnosis, and treatment
      include gonorrhea, Chlamydia trachomatis, Trichomonas vaginalis, syphilis,
      chancroid, Herpes simplex, lymphogranuloma venereum, granuloma inguinale, Herpes
      papilloma virus, Molluscum contagiosum, and pubic lice. 

PMID- 23958359
TI  - Management of human immunodeficiency virus in primary care.
AB  - This article presents an overview of current human immunodeficiency (HIV)
      management for primary care practitioners. Discussion is focused on appropriate
      screening, antiretroviral treatment, opportunistic infection prophylaxis,
      laboratory testing and prevention. Improved screening can identify the 20-25% of
      persons living with HIV in the United States who remain undiagnosed. Expansion of
      treatment recommendations to include all HIV-infected persons and expanded
      opportunities for prophylaxis will likely significantly increase the number of
      persons who receive antiretroviral treatment. Understanding of opportunistic
      infection prophylaxis, proper vaccination, and comorbid risk factor modification
      can improve life expectancy for many patients living with chronic stable HIV
      infection. 

PMID- 23958360
TI  - Tick-borne infections in the United States.
AB  - Patients with illnesses caused by ticks may present with flulike symptoms.
      Physicians should learn how to recognize these illnesses by specific aspects in
      the patients' histories and physical examinations. Prevention of mortality and
      morbidity may depend on correct early diagnosis and treatment. Illness prevention
      may result with early removal of the tick, because infection usually requires 24
      to 48 hours of attachment to the host. A bite from one tick may transmit several
      different pathogens leading to concurrent infections. The prevention of tick
      borne illnesses can start with advice on how to prevent tick bites, especially
      during summer time.

PMID- 23958361
TI  - Methicillin-resistant Staphylococcus aureus infections.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is an increasingly common
      multidrug-resistant clinical pathogen responsible for increasing health costs and
      for patient morbidity and mortality. Presented in this review, the definition,
      cell and molecular biology, epidemiology, prevention, diagnosis, and treatment of
      MRSA infections, including skin and soft tissue infections, bacteremia and
      endocarditis, pneumonia, bone and joint infections, and central nervous system
      infections, are addressed. In the treatment of MRSA, this article highlights
      several common antibiotics that retain activity against different strains of
      MRSA. 

PMID- 23958362
TI  - Community-acquired pneumonia in adults and children.
AB  - This article provides an overview of community-acquired pneumonia in adults and
      children. The epidemiology, causes, clinical presentation, diagnostic testing,
      site-of-care decisions, treatment, possible complications, and prevention of
      pneumonia are discussed. 

PMID- 23958363
TI  - Ear infections: otitis externa and otitis media.
AB  - This article reviews the diagnosis and treatment of acute otitis externa and
      acute otitis media, and will be helpful to primary care physicians who diagnose
      and treat these common diseases in the clinic. The pathophysiology, microbiology,
      clinical features, diagnosis, treatment, prognosis, and complications are
      discussed. 

PMID- 23958364
TI  - Urinary tract infections.
AB  - Clinical presentation helps differentiate between upper and lower urinary tract
      infections (UTIs). UTIs are classified as either complicated or uncomplicated. A
      complicated UTI is associated with an underlying condition that increases the
      risk of failing therapy. Primary laboratory tests for UTIs consist of urinalysis
      and urine culture. The most common pathogen for uncomplicated cystitis and
      pyelonephritis is Escherichia coli. Nitrofurantoin, fosfomycin, and trimethoprim
      sulfamethoxazole are first-line therapies for acute uncomplicated cystitis.
      Decisions regarding antibiotic agents should be individualized based on patients'
      allergies, tolerability, community resistance rates, cost, and availability. 

PMID- 23958365
TI  - Meningitis.
AB  - Meningitis is defined as inflammation of the meninges, in almost all cases
      identified by an abnormal number of white blood cells in the cerebrospinal fluid
      and specific clinical signs/symptoms. Onset may be acute or chronic, and clinical
      symptoms of acute disease develop over hours to days. This article reviews the
      epidemiology, pathophysiology, clinical manifestations, diagnosis, and management
      of acute meningitis, and provides a list of key points for primary care
      practitioners. Aseptic and bacterial meningitis vary significantly and are
      discussed separately. 

PMID- 23958366
TI  - Acute gastroenteritis.
AB  - Acute gastroenteritis is a common infectious disease syndrome, causing a
      combination of nausea, vomiting, diarrhea, and abdominal pain. There are more
      than 350 million cases of acute gastroenteritis in the United States annually and
      48 million of these cases are caused by foodborne bacteria. Traveler's diarrhea
      affects more than half of people traveling from developed countries to developing
      countries. In adult and pediatric patients, the prevalence of Clostridium
      difficile is increasing. Contact precautions, public health education, and
      prudent use of antibiotics are necessary goals in decreasing the prevalence of
      Clostridium difficle. Preventing dehydration or providing appropriate rehydration
      is the primary supportive treatment of acute gastroenteritis. 

PMID- 23958367
TI  - Tuberculosis: an overview.
AB  - Tuberculosis (TB) is still a public health issue; it continues to reign as one of
      the world's deadliest diseases. One-third of the world's population has been
      infected with TB. Identified cases of mycobacterium must be notified in an
      attempt to reduce the public health impact of TB on the population. TB
      transmission occurs via inhalation of droplet nuclei. The most common site for
      the development of TB is the lungs. Treatment of TB depends on whether latent TB
      or active TB is treated. 

PMID- 23958368
TI  - Upper respiratory infections.
AB  - Upper respiratory infections (URIs) are infections of the mouth, nose, throat,
      larynx (voice box), and trachea (windpipe). This article outlines the
      epidemiology, etiology, diagnosis, and management of URIs, including
      nasopharyngitis (common cold), sinusitis, pharyngitis, laryngitis, and
      laryngotracheitis. 

PMID- 23958369
TI  - Beware--use universal precautions for everything!

PMID- 23958370
TI  - Primary care: clinics in office practice devoted to the topic of infectious
      diseases.

PMID- 23958371
TI  - Recommended content of referral letters from general practitioners to specialised
      mental health care: a qualitative multi-perspective study.
AB  - BACKGROUND: In most Western countries, the referral letter forms the basis for
      establishing the priority of patients for specialised health care and for the
      coordination of care between the services. To be able to define the quality of
      referral letters, the potential impact of the quality on the organisation of
      care, and to improve the quality of the letters, we need a multidimensional
      definition of the ideal content. The study's aim was to explore what information
      is seen as most important and should be included in referral letters from primary
      care to specialised mental health care to facilitate prioritisation and planning
      of treatment and follow-up of the patients. METHODS: Based on purposive sampling,
      four mixed discussion groups, which included general practitioners, mental health
      nurses from primary health care, psychiatrists and psychologists from specialised
      mental health care, managers and patient representatives, were formed; they were
      asked to identify the information they considered important in a mental health
      referral letter. In line with the Delphi technique, the importance of the themes
      was later individually rated by the participants. The study was conducted within
      The Western Norway Regional Health Authority. RESULTS: The four groups identified
      174 information themes. After excluding themes that were assessed as duplicates,
      replaceable or less important, 40 themes were suggested, organised in seven
      units. A set of check-off points of essential information is recommended as an
      introduction in the referral letter. CONCLUSION: Compared with general guidelines
      and guidelines for somatic care, the results of this study suggest that the
      referral letter to specialised mental health care should have a larger emphasis
      on the overall treatment plan, on the specific role of specialised health care in
      the continuum of care, and on patient involvement. Further research should
      evaluate the validity of these findings for other patient groups in need of
      integrated care and investigate how the quality of referral letters affects
      patient-related and organisational outcomes. TRIAL REGISTRATION:  TRIAL
      REGISTRATION NUMBER: NCT01374035.

PMID- 23958372
TI  - Morphological evolution, growth mechanism, and magneto-transport properties of
      silver telluride one-dimensional nanostructures.
AB  - Single crystalline one-dimensional (1D) nanostructures of silver telluride
      (Ag2Te) with well-controlled shapes and sizes were synthesized via the
      hydrothermal reduction of sodium tellurite (Na2TeO3) in a mixed solution. The
      morphological evolution of various 1D nanostructures was mainly determined by
      properly controlling the nucleation and growth process of Ag2Te in different
      reaction times. Based on the transmission electron microscopy and scanning
      electron microscopy studies, the formation mechanism for these 1D nanostructures
      was rationally interpreted. In addition, the current-voltage (I-V)
      characteristics as a function of magnetic field of the highly single crystal
      Ag2Te nanowires were systematically measured. From the investigation of I-V
      characteristics, we have observed a rapid change of the current in low magnetic
      field, which can be used as the magnetic field sensor. The magneto-resistance
      behavior of the Ag2Te nanowires with monoclinic structure was also investigated.
      Comparing to the bulk and thin film materials, we found that there is generally a
      larger change in R (T) as the sample size is reduced, which indicates that the
      size of the sample has a certain impact on magneto-transport properties.
      Simultaneously, some possible reasons resulting in the observed large positive
      magneto-resistance behavior are discussed. 

PMID- 23958373
TI  - Ibrutinib and novel BTK inhibitors in clinical development.
AB  - Small molecule inhibitors targeting dysregulated pathways (RAS/RAF/MEK,
      PI3K/AKT/mTOR, JAK/STAT) have significantly improved clinical outcomes in cancer
      patients. Recently Bruton's tyrosine kinase (BTK), a crucial terminal kinase
      enzyme in the B-cell antigen receptor (BCR) signaling pathway, has emerged as an
      attractive target for therapeutic intervention in human malignancies and
      autoimmune disorders. Ibrutinib, a novel first-in-human BTK-inhibitor, has
      demonstrated clinical effectiveness and tolerability in early clinical trials and
      has progressed into phase III trials. However, additional research is necessary
      to identify the optimal dosing schedule, as well as patients most likely to
      benefit from BTK inhibition. This review summarizes preclinical and clinical
      development of ibrutinib and other novel BTK inhibitors (GDC-0834, CGI-560, CGI
      1746, HM-71224, CC-292, and ONO-4059, CNX-774, LFM-A13) in the treatment of B
      cell malignancies and autoimmune disorders. 

PMID- 23958374
TI  - Accelerated partial breast irradiation using 3D conformal radiotherapy: toxicity
      and cosmetic outcome.
AB  - PURPOSE: The aim of this paper is to analyze the incidence of acute and late
      toxicity and cosmetic outcome in breast cancer patients submitted to breast
      conserving surgery and three-dimensional conformal radiotherapy (3D-CRT) to
      deliver accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: 84
      patients were treated with 3D-CRT for APBI. This technique was assessed in
      patients with low risk stage I breast cancer enrolled from September 2005 to July
      2011. The prescribed dose was 34/38.5 Gy delivered in 10 fractions twice daily
      over 5 consecutive days. Four to five no-coplanar 6 MV beams were used. In all CT
      scans Gross Tumor Volume (GTV) was defined around the surgical clips. A 1.5 cm
      margin was added by defining a Clinical Target Volume (CTV). A margin of 1 cm was
      added to CTV to define the planning target volume (PTV). The dose-volume
      constraints were followed in accordance with the NSABP/RTOG protocol. Late
      toxicity was evaluated according to the RTOG grading schema. The cosmetic
      assessment was performed using the Harvard scale. RESULTS: Median patient age was
      66 years (range 51-87). Median follow-up was 36.5 months (range 13-83). The
      overall incidence of acute skin toxicities was 46.4% for grade 1 and 1% for grade
      2. The incidence of late toxicity was 16.7% for grade 1, 2.4% for grade 2 and
      3.6% for grade 3. No grade 4 toxicity was observed. The most pronounced grade 2
      late toxicity was telangiectasia, developed in three patients. Cosmetics results
      were excellent for 52%, good for 42%, fair for 5% and poor for 1% of the
      patients. There was no statistical correlation between toxicity rates and
      prescribed doses (p = 0.33) or irradiated volume (p = 0.45). CONCLUSIONS: APBI
      using 3D-CRT is technically feasible with very low acute and late toxicity. Long
      term results are needed to assess its efficacy in reducing the incidence of
      breast relapse.

PMID- 23958376
TI  - Items and dimensions for the construction of a multidimensional computerized
      adaptive test to measure fatigue in patients with rheumatoid arthritis.
AB  - OBJECTIVES: Development of an item pool to construct a future computerized
      adaptive test (CAT) for fatigue in rheumatoid arthritis (RA). The item pool was
      based on the patients' perspective and examined for face and content validity
      previously. This study assessed the fit of the items with seven predefined
      dimensions and examined the item pool's dimensionality structure in statistical
      terms. STUDY DESIGN AND SETTING: A total of 551 patients with RA participated in
      this study. Several steps were conducted to come from an explorative item pool to
      a psychometrically sound item bank. The item response theory (IRT) analysis using
      the generalized partial credit model was conducted for each of the seven
      predefined dimensions. Poorly fitting items were removed. Finally, the best
      possible multidimensional IRT (MIRT) model for the data was identified. RESULTS:
      In IRT analysis, 49 items showed insufficient item characteristics. Items with a
      discriminative ability below 0.60 and/or model misfit effect sizes greater than
      0.10 were removed. Factor analysis on the 196 remaining items revealed three
      dimensions, namely severity, impact, and variability of fatigue. The dimensions
      were further confirmed in MIRT model analysis. CONCLUSION: This study provided an
      initially calibrated item bank and showed which dimensions and items can be used
      for the development of a multidimensional CAT for fatigue in RA.

PMID- 23958375
TI  - Randomized phase II study of sunitinib versus standard of care for patients with
      previously treated advanced triple-negative breast cancer.
AB  - PURPOSE: This randomized, open-label phase II study compared the efficacy of
      sunitinib monotherapy with that of single-agent standard-of-care (SOC)
      chemotherapy in patients with previously treated advanced triple-negative breast
      cancer (TNBC). METHODS: Patients with advanced TNBC, relapsed after anthracycline
      and taxane-based chemotherapy, were randomized to receive either sunitinib (37.5
      mg/day) or the investigator's choice of SOC therapy. Progression-free survival
      was the primary endpoint. RESULTS: Median progression-free survival was 2.0
      months with sunitinib and 2.7 months with SOC chemotherapy (one-sided P = 0.888).
      Median overall survival was not prolonged with sunitinib (9.4 months) compared
      with SOC chemotherapy (10.5 months; one-sided P = 0.839). The objective response
      rate was 3% with sunitinib and 7% with SOC chemotherapy (one-sided P = 0.962).
      CONCLUSIONS: Sunitinib monotherapy did not improve efficacy compared with SOC
      chemotherapy in patients with previously treated advanced TNBC, for which
      identification of effective treatments and therapeutic targets remains an urgent
      need. TRIAL REGISTRATION: NCT00246571.

PMID- 23958377
TI  - Effective writing and publishing scientific papers, part VII: tables and figures.

PMID- 23958378
TI  - A systematic review classifies sources of bias and variation in diagnostic test
      accuracy studies.
AB  - OBJECTIVE: To classify the sources of bias and variation and to provide an
      updated summary of the evidence of the effects of each source of bias and
      variation. STUDY DESIGN AND SETTING: We conducted a systematic review of studies
      of any design with the main objective of addressing bias or variation in the
      results of diagnostic accuracy studies. We searched MEDLINE, EMBASE, BIOSIS, the
      Cochrane Methodology Register, and Database of Abstracts of Reviews of Effects
      (DARE) from 2001 to October 2011. Citation searches based on three key papers
      were conducted, and studies from our previous review (search to 2001) were
      eligible. One reviewer extracted data on the study design, objective, sources of
      bias and/or variation, and results. A second reviewer checked the extraction.
      RESULTS: We summarized the number of studies providing evidence of an effect
      arising from each source of bias and variation on the estimates of sensitivity,
      specificity, and overall accuracy. CONCLUSIONS: We found consistent evidence for
      the effects of case-control design, observer variability, availability of
      clinical information, reference standard, partial and differential verification
      bias, demographic features, and disease prevalence and severity. Effects were
      generally stronger for sensitivity than for specificity. Evidence for other
      sources of bias and variation was limited.

PMID- 23958379
TI  - Suspected survivor bias in case-control studies: stratify on survival time and
      use a negative control.
AB  - OBJECTIVES: Selection bias in case-control studies occurs when control selection
      is inappropriate. However, selection bias due to improper case sampling is less
      well recognized. We describe how to recognize survivor bias (i.e., selection on
      exposed cases) and illustrate this with an example study. STUDY DESIGN AND
      SETTING: A case-control study was used to analyze the effect of statins on major
      bleedings during treatment with vitamin K antagonists. A total of 110 patients
      who experienced such bleedings were included 18-1,018 days after the bleeding
      complication and matched to 220 controls. RESULTS: A protective association of
      major bleeding for exposure to statins (odds ratio [OR]: 0.56; 95% confidence
      interval: 0.29-1.08) was found, which did not become stronger after adjustment
      for confounding factors. These observations lead us to suspect survivor bias. To
      identify this bias, results were stratified on time between bleeding event and
      inclusion, and repeated for a negative control (an exposure not related to
      survival): blood group non-O. The ORs for exposure to statins increased gradually
      to 1.37 with shorter time between outcome and inclusion, whereas ORs for the
      negative control remained constant, confirming our hypothesis. CONCLUSION: We
      recommend the presented method to check for overoptimistic results, that is,
      survivor bias in case-control studies.

PMID- 23958380
TI  - Lipid profiles in brains from sheep with natural scrapie.
AB  - Prion diseases are fatal neurodegenerative disorders affecting many mammals,
      ovine scrapie being the archetypal prion disease. Several independent studies in
      murine and cell-based models of scrapie have highlighted the presence of a link
      between prion generation and lipid alterations; yet, no data on natural disease
      are available. In this study we investigated levels of total lipids and
      cholesterol as well as profiles of fatty acids in brain homogenates from
      symptomatic and asymptomatic scrapie-infected sheep vs. healthy sheep, all
      belonging to the same flock. Lipid extracts were analyzed by means of gas
      chromatography and high performance liquid chromatography. Data of fatty acids
      were submitted to multivariate statistical analysis to give a picture of the
      brain lipid profiles of sheep. Interestingly, results revealed abnormalities in
      the brain fatty acid unsaturation of infected/symptomatic animals. Significant
      reduction of monoene 18:1 n-9 was detected in brain lipids from
      infected/symptomatic sheep, as compared to healthy and infected/asymptomatic
      animals, and this alteration occurred in combination with a significant increase
      in 18:0 level. The unsupervised Principal Component Analysis showed that
      infected/symptomatic and healthy sheep samples lie in two different regions of
      the plot, infected/asymptomatic lie mostly next to healthy. The increase of
      cerebral saturated fatty acids provides a rough indication of presumed
      alterations in lipid raft domains of nervous cells during scrapie, suggesting
      that they may exist in a notable viscous liquid-ordered state. Such
      physicochemical alteration would have a profound impact on the raft thermodynamic
      properties, its spatial organization, and signal transduction, all potentially
      relevant for prion generation. 

PMID- 23958382
TI  - Analytical comparison between Nixon-Logvinenko's and Jung-Brown's theories of
      slow neurofilament transport in axons.
AB  - This paper develops analytical solutions describing slow neurofilament (NF)
      transport in axons. The obtained solutions are based on two theories of NF
      transport: Nixon-Logvinenko's theory that postulates that most NFs are
      incorporated into a stationary cross-linked network and only a small pool is
      slowly transported and Jung-Brown's theory that postulates a single dynamic pool
      of NFs that are transported according to the stop-and-go hypothesis. The simplest
      two-kinetic state version of the model developed by Jung and Brown was compared
      with the theory developed by Nixon and Logvinenko. The model for Nixon
      Logvinenko's theory included stationary, pausing, and running NF populations
      while the model used for Jung-Brown's theory only included pausing and running NF
      populations. Distributions of NF concentrations resulting from Nixon-Logvinenko's
      and Jung-Brown's theories were compared. In previous publications, Brown and
      colleagues successfully incorporated slowing of NF transport into their model by
      assuming that some kinetic constants depend on the distance from the axon
      hillock. In this paper we defined the average rate of NF transport as the rate of
      motion of the center of mass of radiolabeled NFs. We have shown that for this
      definition, if all kinetic rates are assumed constant, Jung-Brown's theory
      predicts a constant average rate of NF transport. We also demonstrated that Nixon
      Logvinenko's theory predicts slowing of NF transport even if all kinetic rates
      are assumed constant, and the obtained slowing agrees well with published
      experimental data. 

PMID- 23958383
TI  - A cholera model in a patchy environment with water and human movement.
AB  - A mathematical model for cholera is formulated that incorporates direct and
      indirect transmission, patch structure, and both water and human movement. The
      basic reproduction number R0 is defined and shown to give a sharp threshold that
      determines whether or not the disease dies out. Kirchhoff's Matrix Tree Theorem
      from graph theory is used to investigate the dependence of R0 on the connectivity
      and movement of water, and to prove the global stability of the endemic
      equilibrium when R0>1. The type/target reproduction numbers are derived to
      measure the control strategies that are required to eradicate cholera from all
      patches. 

PMID- 23958384
TI  - On the interactions of sensitive and resistant Mycobacterium tuberculosis to
      antibiotics.
AB  - In this work we propose a system of non linear ordinary differential equations
      for the dynamics of Mycobacterium tuberculosis (Mtb) within the host, in order to
      study the role of macrophages, T cells and antibiotics in the control of
      sensitive and resistant Mtb. Conditions for the persistence of sensitive and
      resistant bacteria are given in terms of the secondary infections produced by
      bacteria and macrophages, the immune response, and the antibiotic treatment.
      Model analysis predicts backward bifurcations for certain values of the
      parameters. In this case, the dynamics is characterized by the coexistence of two
      infection states with low and high bacteria load, respectively. 

PMID- 23958385
TI  - Engaging and supporting fathers to promote breast feeding: a concept analysis.
AB  - OBJECTIVE: Empirical evidence demonstrates that fathers have a strong influence
      on a mother's decision to initiate and continue breast feeding. However, no clear
      delineation of what behaviours and attributes constitute father support or
      differentiate it from other kinds of support is provided in the current
      literature. The purpose of this study was to analyse the concept of 'father
      support' in relation to maternity services and broader health settings, thereby
      clarifying meaning to enable comprehension and application in practice,
      education, and research. DESIGN: A concept analysis combining the evolutionary
      model of concept development with the inter-related theoretical, fieldwork and
      analytical phases of the hybrid model of concept development. SETTING: Children's
      Centres in East and West Sussex in Southern England. PARTICIPANTS: Repeated
      qualitative research over two phases with 16 parents of breast fed infants
      through seven focus groups and five telephone interviews. MEASUREMENTS AND
      FINDINGS: CINAHL, PsycINFO, AMED, MEDLINE, OVID and EMBASE databases were
      searched for articles published in English between 1999 and 2013 using the
      keywords breast feeding, father, and support. Seven same-sex focus groups and
      five individual interviews were also conducted over two research phases with the
      parents of breast fed infants to expand and exemplify, and then validate the
      analysis of the literature search. Five main attributes of father support in
      relation to breast feeding were identified: (1) knowledge about breast feeding;
      (2) positive attitude to breast feeding; (3) involvement in the decision-making
      process; (4) practical support; and (5) emotional support. Multiple antecedents
      and consequences to these attributes were also identified. KEY CONCLUSION: This
      study has contributed to clarifying the meaning of father support in relation to
      breast feeding and provides an important starting point for the development of a
      theoretical and practical model of optimal breast feeding that takes into account
      father support. IMPLICATIONS FOR PRACTICE: Identification of attributes,
      antecedents, and consequences of father support may assist practitioners to
      reflect on current working practices and service delivery models, and offer
      important educational opportunities for the training of student midwives and
      other health professionals.

PMID- 23958386
TI  - Development of a community-based maternal, newborn and child emergency training
      package in South Sudan.
AB  - OBJECTIVE: To develop an evidence-based maternal, newborn and child emergency
      training package for community-based frontline health workers (FHWs) in post
      conflict South Sudan. METHODS: In partnership with the new Republic of South
      Sudan, a multimodal needs assessment was conducted through purposive sampling,
      involving key informant interviews, focus group discussions, provider knowledge
      assessments and facility surveys. Data were analyzed using traditional
      qualitative techniques and compared with existing training programmes and
      curricula. These findings informed the development and implementation of the
      novel training approach. RESULTS: The needs assessment involved 33 FHWs, eight
      diverse health facilities in Eastern Equatoria, and stakeholders within 18
      governmental and non-governmental organizations. Significant consensus emerged
      regarding the need for greater capacity among previously untrained FHWs. A
      maternal, newborn and child health training package was developed that included:
      (1) a participatory training course taught through a 'training of trainers'
      approach; (2) nine different pictorial action-based checklists covering basic
      management and referral of maternal, newborn and child emergencies; and (3)
      essential setting-appropriate equipment. CONCLUSION: A novel maternal, newborn
      and child survival package was developed for previously untrained and illiterate
      FHWs in South Sudan. It is hoped that this approach will build community-based
      capacity in resource-limited settings while greater capacity is being developed
      for facility-based deliveries by skilled birth attendants.

PMID- 23958387
TI  - Controlled vocabularies for plant anatomical parts optimized for use in data
      analysis tools and for cross-species studies.
AB  - BACKGROUND: It is generally accepted that controlled vocabularies are necessary
      to systematically integrate data from various sources. During the last decade,
      several plant ontologies have been developed, some of which are community
      specific or were developed for a particular purpose. In most cases, the practical
      application of these ontologies has been limited to systematically storing
      experimental data. Due to technical constraints, complex data structures and term
      redundancies, it has been difficult to apply them directly into analysis tools.
      RESULTS: Here, we describe a simplified and cross-species compatible set of
      controlled vocabularies for plant anatomy, focussing mainly on monocotypledonous
      and dicotyledonous crop and model plants. Their content was designed primarily
      for their direct use in graphical visualization tools. Specifically, we created
      annotation vocabularies that can be understood by non-specialists, are minimally
      redundant, simply structured, have low tree depth, and we tested them practically
      in the frame of Genevestigator. CONCLUSIONS: The application of the proposed
      ontologies enabled the aggregation of data from hundreds of experiments to
      visualize gene expression across tissue types. It also facilitated the comparison
      of expression across species. The described controlled vocabularies are
      maintained by a dedicated curation team and are available upon request.

PMID- 23958388
TI  - Comparison of non-invasive electrohysterographic recording techniques for
      monitoring uterine dynamics.
AB  - Non-invasive recording of uterine myoelectric activity (electrohysterogram, EHG)
      could provide an alternative to monitoring uterine dynamics by systems based on
      tocodynamometers (TOCO). Laplacian recording of bioelectric signals has been
      shown to give better spatial resolution and less interference than mono- and
      bipolar surface recordings. The aim of this work was to study the signal quality
      obtained from monopolar, bipolar and Laplacian techniques in EHG recordings, as
      well as to assess their ability to detect uterine contractions. Twenty-two
      recording sessions were carried out on singleton pregnant women during the active
      phase of labour. In each session the following simultaneous recordings were
      obtained: internal uterine pressure (IUP), external tension of abdominal wall
      (TOCO) and EHG signals (5 monopolar and 4 bipolar recordings, 1 discrete
      approximation to the Laplacian of the potential and 2 estimates of the Laplacian
      from two active annular electrodes). The results obtained show that EHG is able
      to detect a higher number of uterine contractions than TOCO. Laplacian recordings
      give improved signal quality over monopolar and bipolar techniques, reduce
      maternal cardiac interference and improve the signal-to-noise ratio. The optimal
      position for recording EHG was found to be the uterine median axis and the lower
      centre-right umbilical zone. 

PMID- 23958389
TI  - ICRP, 123. Assessment of radiation exposure of astronauts in space. ICRP
      Publication 123.
AB  - During their occupational activities in space, astronauts are exposed to ionising
      radiation from natural radiation sources present in this environment. They are,
      however, not usually classified as being occupationally exposed in the sense of
      the general ICRP system for radiation protection of workers applied on Earth. The
      exposure assessment and risk-related approach described in this report is clearly
      restricted to the special situation in space, and should not be applied to any
      other exposure situation on Earth. The report describes the terms and methods
      used to assess the radiation exposure of astronauts, and provides data for the
      assessment of organ doses. Chapter 1 describes the specific situation of
      astronauts in space, and the differences in the radiation fields compared with
      those on Earth. In Chapter 2, the radiation fields in space are described in
      detail, including galactic cosmic radiation, radiation from the Sun and its
      special solar particle events, and the radiation belts surrounding the Earth.
      Chapter 3 deals with the quantities used in radiological protection, describing
      the Publication 103 (ICRP, 2007) system of dose quantities, and subsequently
      presenting the special approach for applications in space; due to the strong
      contribution of heavy ions in the radiation field, radiation weighting is based
      on the radiation quality factor, Q, instead of the radiation weighting factor,
      wR. In Chapter 4, the methods of fluence and dose measurement in space are
      described, including instrumentation for fluence measurements, radiation
      spectrometry, and area and individual monitoring. The use of biomarkers for the
      assessment of mission doses is also described. The methods of determining
      quantities describing the radiation fields within a spacecraft are given in
      Chapter 5. Radiation transport calculations are the most important tool. Some
      physical data used in radiation transport codes are presented, and the various
      codes used for calculations in high-energy radiation fields in space are
      described. Results of calculations and measurements of radiation fields in
      spacecraft are given. Some data for shielding possibilities are also presented.
      Chapter 6 addresses methods of determining mean absorbed doses and dose
      equivalents in organs and tissues of the human body. Calculated conversion
      coefficients of fluence to mean absorbed dose in an organ or tissue are given for
      heavy ions up to Z=28 for energies from 10 MeV/u to 100 GeV/u. For the same set
      of ions and ion energies, mean quality factors in organs and tissues are
      presented using, on the one hand, the Q(L) function defined in Publication 60
      (ICRP, 1991), and, on the other hand, a Q function proposed by the National
      Aeronautics and Space Administration. Doses in the body obtained by measurements
      are compared with results from calculations, and biodosimetric measurements for
      the assessment of mission doses are also presented. In Chapter 7, operational
      measures are considered for assessment of the exposure of astronauts during space
      missions. This includes preflight mission design, area and individual monitoring
      during flights in space, and dose recording. The importance of the magnitude of
      uncertainties in dose assessment is considered. Annex A shows conversion
      coefficients and mean quality factors for protons, charged pions, neutrons, alpha
      particles, and heavy ions(2 < Z <=2 8), and particle energies up to 100 GeV/u.

PMID- 23958391
TI  - A systematic review and meta-analysis of common mutations of SLC26A4 gene in
      Asian populations.
AB  - OBJECTIVES: The IVS7-2A>G (c.919-2A>G) and p.H723R (c.2168A>G) mutations of
      SLC26A4 gene are recognized as a risk factor for the non-syndromic hearing loss.
      To elucidate the variable results, a meta-analysis and systematic review was
      performed from all case-control studies by pooling data on them. METHODS: The
      case-control studies were assessed with a modification of the Newcastle-Ottawa
      Scale (NOS). The strength of association between c.919-2A>G, c.2168A>G and
      hearing loss risk was measured by odds ratios (ORs) with 95% confidence intervals
      (CIs). RESULTS: We included 14 case-control studies and 16 case series studies in
      present study. There was a higher prevalence of the c.919-2A>G mutation in the
      case group than that in the control group (12.4% vs 0.9%; OR = 13.05, 95% CI:
      8.41-20.23, Z = 11.47, P<0.00001). CONCLUSIONS: In conclusion, the results from
      this meta-analysis suggest that NSHL patients have an increased risk of the c.919
      2A>G mutation of SLC26A4 gene in Asians, especially in Chinese.

PMID- 23958390
TI  - Efficacy and safety of combination therapy with vildagliptin and metformin versus
      metformin up-titration in Chinese patients with type 2 diabetes mellitus: study
      design and rationale of the vision study.
AB  - BACKGROUND AND AIM: Limitations of the currently recommended stepwise treatment
      pathway for type 2 diabetes mellitus (T2DM), especially the failure of
      monotherapies to maintain good glycemic control, have prompted use of early, more
      aggressive combination therapies.The VISION study is designed to explore the
      efficacy and safety of vildagliptin as an add-on to metformin therapy compared
      with up-titration of metformin monotherapy in Chinese patients with T2DM.
      METHODS: VISION, a 24-week, phase 4, prospective, randomized, multicenter, open
      label, parallel-group study, will include 3312 Chinese T2DM patients aged >=18
      years who are inadequately controlled (6.5% >HbA1c <=9%) by metformin (750-1000
      mg/day). Eligible patients will be randomized to receive either vildagliptin plus
      metformin or up-titration of metformin monotherapy (5:1). Patients will also be
      subgrouped (1:1:1:1) based on their age and body mass index (BMI): <60 years and
      <24 kg/m2; <60 years and >=24 kg/m2; >=60 years and <24 kg/m2; and >=60 years and
      >=24 kg/m2. CONCLUSION: The VISION study will test the hypothesis that early use
      of combination therapy with vildagliptin and metformin will provide good glycemic
      control and will be better tolerated than up-titration of metformin monotherapy.
      The study will also correlate these benefits with age and BMI.

PMID- 23958392
TI  - Treatment outcomes of pediatric rhinoplasty: the Asan Medical Center experience.
AB  - OBJECTIVE: Performing rhinoplasty in children has been an issue of some debate
      due to concerns about potential harmful effects on nasoseptal growth. However,
      there is a paucity of evidence describing the outcomes of pediatric rhinoplasty.
      This study presents our experience of performing this procedure in children of 17
      years of age and younger. METHODS: The study population consisted of 64 Korean
      children between 4 and 17 years of age who underwent rhinoplasty between May 2003
      and August 2011. Forty-six of the patients were boys and 18 were girls with a
      mean follow-up period of 59 months. The diagnosis of the patients, the extent of
      the surgical maneuver performed, and the surgical outcomes were reviewed.
      Subjective satisfaction of the patients was investigated by telephone interview.
      Surgical outcomes, which were judged by two independent ENT surgeons, were
      evaluated by comparing preoperative and postoperative photographs. Satisfaction
      scores were graded using a visual analog scale (from 1 = satisfied, to 4 =
      dissatisfied). Anthropometric measurements of nasal parameters were performed
      preoperatively and postoperatively. RESULTS: Rhinoplasty was performed in our
      patient cohort due to a deviated nose (32.8%), nasal bone fracture (18.8%), flat
      nose (6.3%), nasal mass (4.7%), hump nose (3.1%), nasal dermoid sinus cyst
      (1.6%), and additional cosmetic rhinoplasty for planned septoplasty (32.8%). The
      median patient satisfaction score was 2.09 compared with a median doctor
      satisfaction score of 1.81. Anthropometric measurements showed statistically
      significant improvements in nasal tip projection, nasal length, dorsal height,
      and radix height after rhinoplasty. Seventeen patients (26.6%) experienced
      esthetic dissatisfaction such as deviation, tip depression, bulbous tip, short
      nose, and nostril asymmetry. Eight patients (12.5%) experienced postoperative
      difficulty in nasal breathing, and two patients (3.1%) complained of transient
      nasal pain after rhinoplasty. Six patients (9.4%) underwent revision surgery, and
      four patients (6.3%) were seriously considering a revision operation.
      CONCLUSIONS: The outcome analysis in our series reveals that rhinoplasty in
      children is complicated by a high rate of revision and esthetic dissatisfaction.
      The results of this study may indicate that surgeons should have a conservative
      attitude and apply strict indication in selecting pediatric rhinoplasty
      candidates.

PMID- 23958393
TI  - The effect of montelukast on wheal reactions in skin prick tests: a double-blind
      placebo-controlled randomized trial.
AB  - OBJECTIVE: It is well-known that number of drugs may interfere with wheal
      reactions in skin prick test. However, the effect of long-term use of
      montelukast, a cystenil leukotriene receptor antagonist, on skin prick test
      hasn't been full elucidated. The aim of present study was to demonstrate the
      effect of montelukast on skin prick tests (SPT). METHODS: This is a single
      center, randomized, double-blinded, placebo-controlled study including two
      treatment periods with a wash-out interval. The subjects received montelukast (5
      mg per day), fexofenadine HCl (60 mg per day) and placebo (lactose) with a double
      blinded manner during 7- and 21-days treatment periods with a 14 days wash-out
      period. Dermatophagoides farinae (D. farinae) was used as the skin test material,
      while histamine as positive control and normal saline as negative control.
      Overall, 7 skin prick tests were performed at following time points: before
      treatment periods, on the last days of both treatment periods, 24 h after
      completion of treatment periods, and on the last day of 14-days interval.
      RESULTS: Sixty house dust mite (HDM) allergic children (23 girls and 37 boys)
      with allergic rhinitis and/or asthma completed the study. Mean age was 8.3 +/-
      2.0 years. In the fexofenadine group, a significant suppression was observed in
      post-treatment values when compared to baseline values in SPT with D. farinae (p
      = 0.019). In the montelukast group, no significant suppression was observed in
      SPT with D. farinae at all time points when compared to baseline. CONCLUSIONS:
      Our results showed that montelukast had no effect on measurements of SPT. Thus,
      we concluded that there is no need to discontinue the treatment in order to
      perform SPT in patients receiving montelukast, even in those on montelukast
      treatment for at least 21 days.

PMID- 23958394
TI  - PAX8: a sensitive and specific marker to identify cancer cells of ovarian origin
      for patients prior to neoadjuvant chemotherapy.
AB  - BACKGROUND: Neoadjuvant chemotherapy followed by cytoreduction surgery has been
      used where an accurate cytologic or pathologic diagnosis is usually required
      before the initiation of neoadjuvant chemotherapy. However, it is difficult to
      make definitive diagnosis of presence of cancer cells, particularly gynecologic
      versus non-gynecologic origin, from those ascites specimens due to the absence of
      specific biomarkers of gynecologic cancers. In the present study, we evaluated
      if, in addition to the routine morphologic diagnosis, the biomarker PAX8 could be
      useful in recognition of ovarian epithelial cancer cells prior to the neoadjuvant
      chemotherapy. METHODS: Two hundred and two cytology specimens including 120
      pretreatment ovarian cancer samples, 60 benign controls, and 22 malignant non
      gynecologic cases were studied. All cytology slides were morphologically reviewed
      in a blinded fashion without knowing corresponding pathology diagnosis, if
      present. A total of 168 cytology specimens with a cell block were stained with
      PAX8 and Calretinin. These included patients with potential for ovarian cancer
      neoadjuvant chemotherapy (n=96), metastatic cancers (n=22), and benign controls
      (n=50). RESULTS: Among the 96 ascitic samples prior to neoadjuvant chemotherapy,
      76 (79%) showing morphologic features consistent with cancers of ovarian primary
      were all PAX+/Calretinin-. The remaining 20 (21%) cases were positive for
      adenocarcinoma, but morphologically unable to be further classified. Among the 22
      metastatic cancers into the pelvis, one case with PAX8+/Calretinin- represented a
      renal cell carcinoma and the remaining 21 PAX8-/Calretinin- metastatic cancers
      were either breast metastasis (n=4) and the metastasis from gastrointestinal
      tract (n=17). Among the 50 benign control pelvic washing cases, 5
      PAX8+/Calretinin-cases represented endosalpingiosis (n=4) and endometriosis
      (n=1), 25 PAX8-/Calretinin+cases showed reactive mesothelial cells, and the
      remaining 20 specimens with PAX8-/Calretinin- phenotype typically contained
      inflammatory or blood cells without noticeable diagnostic epithelia. CONCLUSIONS:
      PAX8 identifies all Mullerian derived benign or malignant epithelia. When
      combining with Calretinin, PAX8 is a sensitive marker to diagnose the carcinomas
      of ovarian origin, which will be ideal to be used for those patients with a
      possible advanced ovarian cancer prior to receiving neoadjuvant chemotherapy.

PMID- 23958395
TI  - Patient identification errors: the detective in the laboratory.
AB  - BACKGROUND: The eradication of errors regarding patients' identification is one
      of the main goals for safety improvement. As clinical laboratory intervenes in
      70% of clinical decisions, laboratory safety is crucial in patient safety. We
      studied the number of Laboratory Information System (LIS) demographic data errors
      registered in our laboratory during one year. METHODS: The laboratory attends a
      variety of inpatients and outpatients. The demographic data of outpatients is
      registered in the LIS, when they present to the laboratory front desk. The
      requests from the primary care centers (PCC) are made electronically by the
      general practitioner. A manual step is always done at the PCC to conciliate the
      patient identification number in the electronic request with the one in the LIS.
      Manual registration is done through hospital information system demographic data
      capture when patient's medical record number is registered in LIS. Laboratory
      report is always sent out electronically to the patient's electronic medical
      record. Daily, every demographic data in LIS is manually compared to the request
      form to detect potential errors. RESULTS: Fewer errors were committed when
      electronic order was used. There was great error variability between PCC when
      using the electronic order. CONCLUSIONS: LIS demographic data manual registration
      errors depended on patient origin and test requesting method. Even when using the
      electronic approach, errors were detected. There was a great variability between
      PCC even when using this electronic modality; this suggests that the number of
      errors is still dependent on the personnel in charge of the technology.

PMID- 23958397
TI  - Older smokers could be the strongest supporters for U.S. government regulation of
      tobacco: a focus group study.
AB  - BACKGROUND: Targeting of marginalized groups with aggressive tobacco marketing
      has been identified as exacerbating health disparities. However, interpretation
      of such targeting by groups varies, from surprise and outrage to regarding such
      marketing as evidence of social legitimacy. We sought to learn how an often
      overlooked marginalized group, older adults, would respond to industry documents
      offering evidence of tobacco company target marketing. METHODS: We conducted 10
      focus groups in California cities with older (>=50 years) smokers and former
      smokers. A set of previously-undisclosed tobacco industry documents related to
      target marketing was shown to the group in sequence. Audiotaped discussions were
      transcribed and data analyzed using qualitative approaches. RESULTS: Responses to
      evidence of tobacco industry targeting varied, with some regarding it as
      exploitive and others as normal business practice. However, in most groups,
      discussions turned to government's failure to protect the public-even though
      government action /inaction was not prompted nor addressed in the discussion
      documents. CONCLUSION: Given the Food and Drug Administration's new authority to
      regulate tobacco products, these findings suggest that some of the tobacco
      industry's "best customers" (older, established smokers and ex-smokers) may be
      strong supporters of government regulation of tobacco.

PMID- 23958398
TI  - How one TSH receptor antibody induces thyrocyte proliferation while another
      induces apoptosis.
AB  - Thyroid stimulating hormone (TSH) activates two major G-protein arms, Gsalpha and
      Gq leading to initiation of down-stream signaling cascades for survival,
      proliferation and production of thyroid hormones. Antibodies to the TSH receptor
      (TSHR-Abs), found in patients with Graves' disease, may have stimulating,
      blocking, or neutral actions on the thyroid cell. We have shown previously that
      such TSHR-Abs are distinct signaling imprints after binding to the TSHR and that
      such events can have variable functional consequences for the cell. In
      particular, there is a great contrast between stimulating (S) TSHR-Abs, which
      induce thyroid hormone synthesis and secretion as well as thyroid cell
      proliferation, compared to so called "neutral" (N) TSHR-Abs which may induce
      thyroid cell apoptosis via reactive oxygen species (ROS) generation. In the
      present study, using a rat thyrocyte (FRTL-5) ex vivo model system, our
      hypothesis was that while N-TSHR-Abs can induce apoptosis via activation of
      mitochondrial ROS (mROS), the S-TSHR-Abs are able to stimulate cell survival and
      avoid apoptosis by actively suppressing mROS. Using fluorescent microscopy,
      fluorometry, live cell imaging, immunohistochemistry and immunoblot assays, we
      have observed that S-TSHR-Abs do indeed suppress mROS and cellular stress and
      this suppression is exerted via activation of the PKA/CREB and AKT/mTOR/S6K
      signaling cascades. Activation of these signaling cascades, with the suppression
      of mROS, initiated cell proliferation. In sharp contrast, a failure to activate
      these signaling cascades with increased activation of mROS induced by N-TSHR-Abs
      resulted in thyroid cell apoptosis. Our current findings indicated that signaling
      diversity induced by different TSHR-Abs regulated thyroid cell fate. While S-TSHR
      Abs may rescue cells from apoptosis and induce thyrocyte proliferation, N-TSHR
      Abs aggravate the local inflammatory infiltrate within the thyroid gland, or in
      the retro-orbit, by inducing cellular apoptosis; a phenomenon known to activate
      innate and by-stander immune-reactivity via DNA release from the apoptotic cells.

PMID- 23958399
TI  - Triamterene crystalline nephropathy.
AB  - Medications can cause a tubulointerstitial insult leading to acute kidney injury
      through multiple mechanisms. Acute tubular injury, a dose-dependent process,
      occurs due to direct toxicity on tubular cells. Acute interstitial nephritis
      characterized by interstitial inflammation and tubulitis develops from drugs that
      incite an allergic reaction. Other less common mechanisms include osmotic
      nephrosis and crystalline nephropathy. The latter complication is rare but has
      been associated with several drugs, such as sulfadiazine, indinavir,
      methotrexate, and ciprofloxacin. Triamterene crystalline nephropathy has been
      reported only rarely, and its histologic characteristics are not well
      characterized. We report 2 cases of triamterene crystalline nephropathy, one of
      which initially was misdiagnosed as 2,8-dihydroxyadenine crystalline nephropathy.

PMID- 23958396
TI  - Evading apoptosis in cancer.
AB  - Carcinogenesis is a mechanistically complex and variable process with a plethora
      of underlying genetic causes. Cancer development comprises a multitude of steps
      that occur progressively starting with initial driver mutations leading to
      tumorigenesis and, ultimately, metastasis. During these transitions, cancer cells
      accumulate a series of genetic alterations that confer on the cells an
      unwarranted survival and proliferative advantage. During the course of
      development, however, cancer cells also encounter a physiologically ubiquitous
      cellular program that aims to eliminate damaged or abnormal cells: apoptosis.
      Thus, it is essential that cancer cells acquire instruments to circumvent
      programmed cell death. Here we discuss emerging evidence indicating how cancer
      cells adopt various strategies to override apoptosis, including amplifying the
      antiapoptotic machinery, downregulating the proapoptotic program, or both. 

PMID- 23958400
TI  - Glycated hemoglobin and risk of death in diabetic patients treated with
      hemodialysis: a meta-analysis.
AB  - BACKGROUND: Studies investigating the association between glycated hemoglobin
      (HbA1c) level and mortality risk in diabetic patients receiving hemodialysis have
      shown conflicting results. STUDY DESIGN: We conducted a systematic review and
      meta-analysis using MEDLINE, EMBASE, Web of Science, and the Cochrane Library.
      SETTING & POPULATION: Diabetic patients on maintenance hemodialysis therapy.
      SELECTION CRITERIA FOR STUDIES: Observational studies or randomized controlled
      trials investigating the association between HbA1c values and mortality risk.
      Study authors were asked to provide anonymized individual patient data or
      reanalyze results according to a standard template. PREDICTOR: Single measurement
      or mean HbA1c values. Mean HbA1c values were calculated using all individual
      patient HbA1c values during the follow-up period of contributing studies.
      OUTCOME: HR for mortality risk. RESULTS: 10 studies (83,684 participants) were
      included: 9 observational studies and one secondary analysis of a randomized
      trial. After adjustment for confounders, patients with baseline HbA1c levels >=
      8.5% (>= 69 mmol/mol) had increased mortality (7 studies; HR, 1.14; 95% CI, 1.09
      1.19) compared with patients with HbA1c levels of 6.5%-7.4% (48-57mmol/mol).
      Likewise, patients with a mean HbA1c value >= 8.5% also had a higher adjusted
      risk of mortality (6 studies; HR,1.29; 95% CI, 1.23-1.35). There was a small but
      nonsignificant increase in mortality associated with mean HbA1c levels <= 5.4%
      (<= 36 mmol/mol; 6 studies; HR, 1.09; 95% CI, 0.89-1.34). Sensitivity analyses in
      incident (<= 90 days of hemodialysis) and prevalent patients (>90 days of
      hemodialysis) showed a similar pattern. In incident patients, mean HbA1c levels
      <= 5.4% also were associated with increased mortality risk (4 studies; HR, 1.29;
      95% CI, 1.23-1.35). LIMITATIONS: Observational study data and inability to adjust
      for diabetes type in all studies. CONCLUSIONS: Despite concerns about the utility
      of HbA1c measurement in hemodialysis patients, high levels (>= 8.5%) are
      associated with increased mortality risk. Very low HbA1c levels (<= 5.4%) also
      may be associated with increased mortality risk.

PMID- 23958401
TI  - Day-to-day variability in spot urine albumin-creatinine ratio.
AB  - BACKGROUND: Accurate quantification of albuminuria is important in the diagnosis
      and management of chronic kidney disease. The reference test, a timed urinary
      albumin excretion, is cumbersome and prone to collection errors. Spot urine
      albumin-creatinine ratio (ACR) is convenient and commonly used, but random day-to
      day variability in ACR measurements has not been assessed. STUDY DESIGN:
      Prospective cohort study of day-to-day variability in spot urine ACR
      measurements. SETTING & PARTICIPANTS: Clinically stable outpatients (N = 157)
      attending a university hospital clinic in Australia between July 2007 and April
      2010. OUTCOMES: Spot urine ACR variability was assessed and repeatability limits
      were determined using fractional polynomials. MEASUREMENTS: ACRs were measured
      from spot urine samples collected at 9:00 am on consecutive days and 24-hour
      urine albuminuria was measured concurrently. RESULTS: Paired ACRs were obtained
      from 157 patients (median age, 56 years; 60% men; median daily albumin excretion,
      226 [range, 2.5-14,000] mg/d). Day-to-day variability was substantial and
      increased in absolute terms, but decreased in relative terms, with increasing
      baseline ACR. For patients with normoalbuminuria (ACR < 3 mg/mmol [<27 mg/g]), a
      change greater than +/-467% (0-17 mg/mmol [0-150 mg/g]) is required to indicate a
      significant change in albuminuria status with 95% certainty; for those with
      microalbuminuria (ACR of 3-30 mg/mmol [27-265 mg/g]), a change of +/-170% (0-27
      mg/mmol [0-239 mg/g]) is required; for those with macroalbuminuria (ACR > 30
      mg/mmol [>265 mg/g]), a change of +/-83% (5-55 mg/mmol [44-486 mg/g]) is
      required; and for those with nephrotic-range proteinuria (ACR > 300 mg/mmol
      [>2,652 mg/g]), a change of +/-48% (158-443 mg/mmol [1,397-3,916 mg/g]) is needed
      to represent a significant change. LIMITATIONS: These study results need to be
      replicated in other ethnic groups. CONCLUSIONS: Changes in chronic kidney disease
      status attributed to therapy or disease progression, when based solely on a
      change in ACR, may be incorrect unless the potential for day-to-day biological
      variation has been considered. Only relatively large changes are likely to
      indicate a change in disease status.

PMID- 23958402
TI  - In vitro susceptibility of Conidiobolus lamprauges recovered from sheep to
      antifungal agents.
AB  - Data regarding the susceptibility of Conidiobolus lamprauges is limited and there
      is no consensus about the optimal treatment for infections caused by Conidiobolus
      spp. In this context, the objective of this study was to evaluate the in vitro
      susceptibility of six C. lamprauges strains isolated from sheep
      conidiobolomycosis to amphotericin B, ketoconazole, fluconazole, itraconazole,
      posaconazole, voriconazole, anidulafungin, caspofungin, micafungin, flucytosine,
      and terbinafine using the CLSI M38-A2 microdilution technique. Terbinafine was
      the most active (MIC range <0.06-0.5 MUg/mL). Resistance or reduced
      susceptibility was observed for amphotericin B and azole and echinocandin
      antifungals. Additional studies are necessary to determine the therapeutic
      potential of terbinafine as monotherapy or in combination therapy with other
      antifungals.

PMID- 23958403
TI  - LuxS contributes to virulence in avian pathogenic Escherichia coli O78:K80:H9.
AB  - Avian pathogenic Escherichia coli (APEC) cause avian colibacillosis, a poultry
      disease characterized by multiple organ infections resulting in significant
      economic loss in the poultry industry. Several virulence factors are important
      for disease manifestation in APEC of which, role of quorum sensing has not been
      investigated. Quorum sensing is a population dependent cell-cell signaling system
      which modulates numerous physiological processes such as biofilm formation and
      virulence in multiple species. LuxS, a well-known controller in the QS, plays a
      role in regulating virulence in various bacterial species. Here we investigated
      the role of LuxS in regulating virulence in APEC O78:K80:H9. Mutation of luxS
      resulted in a significant reduction of virulence in APEC O78:K80:H9, evidenced by
      both in vivo and in vitro assays such as decreased invasion of internal organs in
      chicken embryo, reduced lethality in chicken embryo lethality assay, and altered
      lipopolysaccharide (LPS) profile. In addition, the abilities of the knockout
      strain to survive in chicken macrophage cell lines and to invade in chicken
      embryo fibroblast cells were significantly diminished. Further, structure and
      expression level of the LPS profile was significantly altered in the knockout
      strain, which may be one of the contributing factors for the persistence and
      virulence of APEC. Complementation of luxS gene in trans restored the virulence
      of the knockout strain to the level of wild-type bacteria. Taken together, these
      results show that LuxS contributes to the virulence in APEC O78:K80:H9 strain and
      partly explain the role played by LuxS in the pathogenesis of APEC strains. 

PMID- 23958404
TI  - Identification of cattle carrying alleles associated with resistance and
      susceptibility to the Bovine Leukemia Virus progression by real-time PCR.
AB  - Previous studies have shown a significant association between polymorphisms of
      the BoLA DRB3 gene and Bovine Leukemia Virus (BLV) infection profile. The
      presence of allele *1501 has been associated with high proviral load in
      peripheral blood while allele *0902 has been associated with low proviral load.
      The purpose of this study was to develop allele-specific real-time PCRs to
      identify cattle carrying alleles associated with resistance (BoLA DRB3*0902) or
      susceptibility (BoLA DRB3*1501) to the BLV progression. Specific primers were
      designed and differential amplification was carried out by real-time PCR and
      monitored by SYBR(r) Green dye in DNA samples from peripheral blood. Conditions
      were also adjusted for traditional PCR amplification (end point amplification).
      These methods are rapid, simple and suitable for high throughput screening, and
      could aid in marker-assisted selection of BLV-resistant and susceptible cattle.

PMID- 23958405
TI  - Physical activity growth curves relate to adiposity in adolescents.
AB  - PURPOSE: Findings from prospective studies on associations between physical
      activity and adiposity among youth are inconsistent. Our aim was to describe
      physical activity trajectories during secondary school and examine the
      association with change in adiposity in youth. METHODS: Physical activity was
      measured in 20 survey cycles from 1999 to 2005; anthropometrics were measured in
      survey cycles 1, 12, and 19. Individual growth curves modeling moderate-to
      vigorous physical activity (MVPA) and vigorous physical activity (VPA) were
      estimated. Estimates of initial level and rate of decline in MVPA and VPA bouts
      per week were included as potential predictors of body fat% and body mass index
      using age- and sex-specific linear regression. RESULTS: Complete data were
      available for 840 and 760 adolescents aged 12-13 years at baseline, followed from
      survey cycles 1-12 and 12-19, respectively. Among girls, yearly declines of one
      MVPA and one VPA bout per week during earlier adolescence were associated with
      increases of 0.19 (95% confidence interval [CI], 0.02-0.36) and 0.47 (95% CI,
      0.015-0.92) units of body fat%, respectively. In boys, a yearly decline of one
      MVPA bout per week was associated with an increase of 0.38 (95% CI, 0.05-0.70)
      units of body fat% during later adolescence. CONCLUSIONS: Obesity prevention
      programs should include strategies to prevent declines in physical activity.

PMID- 23958406
TI  - Using quadratic inference functions to determine the factors associated with
      obesity: findings from the STEPS Survey in Iran.
AB  - PURPOSE: The last study that had a representative sample of the Iranian
      population and examined the association between sociodemographic and lifestyle
      factors with obesity used data from the 1999 to 2000 National Health Survey in
      Iran. Concern about the increased prevalence of obesity has heightened interest
      in the association between varieties of these factors with obesity among Iranian
      households. METHODS: Data (20,917 adults) were taken from the 2009 STEPwise
      approach to Surveillance survey in Iran that was conducted under the supervision
      of World Health Organization. Using quadratic inference function, we evaluated
      the relation of age, sex, physical activity, serving of fruit and vegetable,
      employment status, smoking, and place of residence with obesity. RESULTS: Using
      20-30 years as the reference group, the obesity odds ratios (ORs) were 2.48,
      3.79, 3.52, and 3.15 for ages 30-40, 40-50, 50-60, and 60+ years, respectively.
      Obesity OR for female was 2.63, compared with male. Obesity ORs for smokers and
      ex-smokers were 0.64 and 1.18, respectively, compared with nonsmokers. Among
      Iranian adult, obesity ORs for the moderate and vigorous physical activity were
      0.99 and 0.90, respectively, compared with low level. The estimated odds of
      obesity were 46% higher for rural adults. Obesity ORs for public and private
      employed were 0.79 and 0.76, respectively, compared with unemployed. CONCLUSIONS:
      Our results may provide better insights of the factors associated with obesity
      and can be used as a basis to reinforce health programs to prevent obesity in
      Iran.

PMID- 23958407
TI  - Effects of calcium and vitamin D supplementation on blood pressure and serum
      lipids and carotenoids: a randomized, double-blind, placebo-controlled, clinical
      trial.
AB  - PURPOSE: To estimate the effects of calcium or vitamin D supplementation or a
      combination of both on blood pressure and serum lipid and carotenoid levels.
      METHODS: Ninety-two colorectal adenoma patients were randomized in a pilot,
      double-blind, placebo-controlled clinical trial of supplemental vitamin D3 800 IU
      and elemental calcium 2.0 g (as calcium carbonate) alone or in combination in
      divided doses twice daily with meals over 6 months. RESULTS: Relative to placebo,
      mean serum triglycerides decreased 30% (P = .10) and 32% (P = .10) in the calcium
      and calcium plus vitamin D3 treatment groups, respectively. When the two calcium
      intervention groups were pooled and compared with the pooled noncalcium groups,
      the estimated supplemental calcium treatment effects were statistically
      significant for triglycerides (P = .04). Similar but nonstatistically significant
      decreases (5%-7%) were observed for serum total cholesterol levels. Mean systolic
      blood pressure increased 6% (P = .08) in the calcium group; otherwise, there were
      no appreciable changes in systolic or diastolic blood pressures in any active
      treatment group. Mean serum total carotenoid levels decreased 14% (P = .07) in
      the calcium and 9% (P = .10) in the calcium plus vitamin D3 groups. CONCLUSIONS:
      Our results suggest that supplemental calcium alone or combined with vitamin D3
      but not vitamin D3 alone may reduce serum lipids and lipophilic micronutrients.

PMID- 23958408
TI  - Eating disorders and anabolic androgenic steroids in males--similarities and
      differences in self-image and psychiatric symptoms.
AB  - BACKGROUND: Body dissatisfaction is common among both females and males.
      Dissatisfaction with the body is a risk factor both for onset of eating disorders
      and for abuse of anabolic androgenic steroids (AAS). Few studies have however
      investigated if there are other similarities in respect to self-image or
      psychiatric symptoms between clinical samples of eating disordered males and
      males in treatment for negative effects of AAS use. AIM: The aim of this study
      was to compare two clinical samples, one of males with ED and one of males who
      used AAS, regarding self-image and psychiatric symptoms. METHODS: This study
      compared males with eating disorders (n = 13) and males who recently stopped AAS
      use (n = 29) on self-image and psychiatric symptoms, using The Structural
      Analysis of Social Behavior self-questionnaire and a shortened version of The
      Symptom Check List. RESULTS: The eating disorder group reported significantly
      lower scores for Self-emancipation and Active self-love and higher scores for
      Self-blame and Self-hate. Both groups reported serious psychiatric symptoms. The
      common denominator between groups was serious psychiatric symptomatology rather
      than negative self-image. CONCLUSIONS: The negative self-image profile,
      especially self-hate, found among males with Eating Disorders may indicate that
      the studied groups differ in aetiology of the underlying problems. The serious
      psychiatric symptoms in both groups call staff to pay attention to any thoughts
      of suicide due to severe depressive symptoms where by specialized psychiatric
      treatment may be needed.

PMID- 23958409
TI  - Non-invasive positive pressure ventilation in children.
AB  - Non-invasive positive pressure ventilation is increasingly used in children both
      in acute and in chronic setting. Clinical data supporting safety, efficacy and
      limitations in children are growing. Technical problems related to the
      ventilators performance and interfaces selection have not been fully resolved,
      especially for younger children. Non-invasive ventilation can be applied at home.
      Its use at home requires appropriate diagnostic procedures, accurate titration of
      the ventilators, cooperative and educated families and careful, well-organized
      follow-up programs. 

PMID- 23958410
TI  - Significance of DNA polymerase I in in vivo processing of clustered DNA damage.
AB  - We examined the biological consequences of bi-stranded clustered damage sites,
      consisting of a combination of DNA lesions, such as a 1-nucleotide gap (GAP), an
      apurinic/apyrimidinic (AP) site, and an 8-oxo-7,8-dihydroguanine (8-oxoG), using
      a bacterial plasmid-based assay. Following transformation with the plasmid
      containing bi-stranded clustered damage sites into the wild type strain of
      Escherichia coli, transformation frequencies were significantly lower for the bi
      stranded clustered GAP/AP lesions (separated by 1bp) than for either a single GAP
      or a single AP site. When the two lesions were separated by 10-20bp, the
      transformation efficiencies were comparable with those of the single lesions.
      This recovery of transformation efficiency for separated lesions requires DNA
      polymerase I (Pol I) activity. Analogously, the mutation frequency was found to
      depend on the distance separating lesions in a bi-stranded cluster containing a
      GAP and an 8-oxoG, and Pol I was found to play an important role in minimising
      mutations induced as a result of clustered lesions. The mutagenic potential of 8
      oxoG within the bi-stranded lesions does not depend on whether it is situated on
      the leading or lagging strand. These results indicate that the biological
      consequences of clustered DNA damage strongly depend on the extent of repair of
      the strand breaks as well as the DNA polymerase in lesion-avoidance pathways
      during replication. 

PMID- 23958411
TI  - Potential roles for DNA replication and repair functions in cell killing by
      streptomycin.
AB  - The aminoglycoside streptomycin binds to ribosomes to promote mistranslation and
      eventual inhibition of translation. Streptomycin kills bacteria, whereas many
      other non-aminoglycoside inhibitors of translation do not. Because mistranslation
      is now known to affect DNA replication, we asked if hydroxyurea, a specific
      inhibitor of DNA synthesis, affects killing, and find that hydroxyurea
      significantly attenuates killing by streptomycin. We find that the hydroxyl
      radical scavengers d-mannitol and thiourea have either no effect or only a modest
      protective effect. The iron chelator 2,2'-dipyridyl eliminated killing by
      streptomycin, but further investigation revealed that it blocks streptomycin
      uptake. Prior treatment of cells with low-levels of methyl methanesulfonate to
      induce the adaptive response to alkylation leads to a significant attenuation of
      killing, which, together with the hydroxyurea effect, suggests roles for DNA
      replication and repair functions in cell killing by streptomycin. 

PMID- 23958413
TI  - Improved cryopreservation protocol for Blanca-Celtiberica buck semen collected by
      electroejaculation.
AB  - The collection of sperm samples by electroejaculation (EE) leads to an increase
      of the production of seminal plasma which could modify the tolerance of
      spermatozoa to the cryopreservation procedure. This study aims to compare a
      standard sperm cryopreservation protocol for samples collected by artificial
      vagina (AV) with the same protocol and modifications to this for samples obtained
      by EE. Semen from six males of Blanca-Celtiberica goat breed was collected by AV
      (control) and EE, and three experiments were conducted. In Experiment 1, it was
      examined the effects of egg yolk concentration contained in freezing extender
      (0%, 1.5%, 10% and 20% of egg yolk); in Experiment 2, it was evaluated the
      cooling rate from 30 to 5  degrees C (fast: 10 min and slow: 90 min) and the
      temperature of glycerol addition (30 and 5  degrees C); and in Experiment 3, it
      was examined the time of equilibration at 5  degrees C (0, 1, 2 or 3h). A
      heterologous in vitro fertilization test was carried out in order to compare the
      fertility of control samples with that resulting from the EE protocol which
      showed the highest sperm quality. Results showed greater sperm motility
      parameters after thawing for control samples cryopreserved in standard conditions
      in the three experiments. For samples collected by EE, extender with 20% egg
      yolk, a slow cooling rate and a longer equilibration time (3h) provided higher
      sperm quality, and no differences were observed between temperatures of glycerol
      addition. Samples collected by EE and cryopreserved with the protocol which
      yielded the best sperm quality after thawing showed higher fertility compared to
      AV.

PMID- 23958414
TI  - Acute rheumatic fever: over-estimation or mis-conception?

PMID- 23958412
TI  - Nuclear dynamics of radiation-induced foci in euchromatin and heterochromatin.
AB  - Repair of double strand breaks (DSBs) is essential for cell survival and genome
      integrity. While much is known about the molecular mechanisms involved in DSB
      repair and checkpoint activation, the roles of nuclear dynamics of radiation
      induced foci (RIF) in DNA repair are just beginning to emerge. Here, we summarize
      results from recent studies that point to distinct features of these dynamics in
      two different chromatin environments: heterochromatin and euchromatin. We also
      discuss how nuclear architecture and chromatin components might control these
      dynamics, and the need of novel quantification methods for a better description
      and interpretation of these phenomena. These studies are expected to provide new
      biomarkers for radiation risk and new strategies for cancer detection and
      treatment. 

PMID- 23958415
TI  - Reciprocal regulation of NO signaling and TXNIP expression in humans: impact of
      aging and ramipril therapy.
AB  - BACKGROUND: Impaired tissue responsiveness to nitric oxide (NO) occurs in many
      cardiovascular diseases as well as with advanced age and is a correlate of poor
      outcomes. This phenomenon results from oxidative stress, with NO "scavenging" and
      dysfunction of soluble guanylate cyclase (sGC). Thioredoxin-interacting protein
      (TXNIP) is a major intracellular regulator of inflammatory activation and redox
      stress, but its interactions with NO/sGC are poorly understood. We have now
      evaluated the relationship between platelet TXNIP expression and function of the
      NO/sGC axis in subjects of varying age and during therapy with ramipril. METHODS
      & RESULTS: Young (n=42) and aging (n=49) subjects underwent evaluation of
      platelet TXNIP content. Aging subjects additionally had measurements of platelet
      NO responsiveness and routine biochemistry. Platelet TXNIP content was greater
      (376+/-33 units) in the aging compared to younger subjects (289+/-13 units;
      p<0.05). In the aging subjects there was a significant negative correlation (r=
      0.50, p<0.001) between platelet TXNIP content and NO responsiveness. In a
      separate cohort of 15 subjects two week treatment with ramipril, which reversed
      platelet NO resistance and potentiated sGC activity, also decreased platelet
      TXNIP content by 40% (p=0.011). CONCLUSIONS: Platelet TXNIP content increases
      with aging, varies inversely with responsiveness to NO, and diminishes rapidly
      following treatment with ramipril. These data suggest that TXNIP-induced
      oxidative stress may be a critical modulator of tissue resistance to NO, a
      fundamental basis for cardiovascular disease. Analogously suppression of TXNIP
      expression can potentially be utilized as an index of restoration of
      cardiovascular homeostasis.

PMID- 23958416
TI  - Human immunodeficiency virus and left ventricular noncompaction.

PMID- 23958417
TI  - A comparison of clinical characteristics and long-term prognosis in asymptomatic
      and symptomatic patients with first-diagnosed atrial fibrillation: the Belgrade
      Atrial Fibrillation Study.
AB  - BACKGROUND: To investigate baseline characteristics and long-term prognosis of
      carefully characterized asymptomatic and symptomatic patients with atrial
      fibrillation (AF) in a 'real-world' cohort of first-diagnosed non-valvular AF
      over a 10-year follow-up period. METHODS AND RESULTS: We conducted an
      observational, non-interventional, and single-centre registry-based study of
      consecutive first-diagnosed AF patients. Of 1100 patients (mean age 52.7+/-12.2
      years and mean follow-up 9.9+/-6.1 years), 146 (13.3%) had asymptomatic AF.
      Persistent or permanent AF, slower ventricular rate during AF (<100/min), CHA2DS2
      VASc score of 0, history of diabetes mellitus and male gender were independent
      baseline risk factors for asymptomatic AF presentation (all p<0.01) with a good
      predictive ability of the multivariable model (c-statistic 0.86, p<0.001). Kaplan
      Meier 10-year estimates of survival free of progression of AF (log-rank
      test=33.4, p<0.001) and ischemic stroke (log-rank test=6.2, p=0.013) were
      significantly worse for patients with asymptomatic AF compared to those with
      symptomatic arrhythmia. In the multivariable Cox regression analysis,
      intermittent asymptomatic AF was significantly associated with progression to
      permanent AF (Hazard Ratio 1.6; 95% CI, 1.1-2.2; p=0.009). CONCLUSIONS: In a
      'real-world' setting, patients with asymptomatic presentation of their first
      diagnosed AF could have different risk profile and long-term outcomes compared to
      those with symptomatic AF. Whether more intensive monitoring and comprehensive AF
      management including AF ablation at early stage following the incident episode of
      AF and increased quality of oral anticoagulation could alter the long-term
      prognosis of these patients requires further investigation.

PMID- 23958418
TI  - Age-related inflammatory mediators in coronary artery disease (II).

PMID- 23958419
TI  - Diagnostic accuracy of three-dimensional contrast-enhanced MR angiography at 3-T
      for acute pulmonary embolism detection: comparison with multidetector CT
      angiography.
AB  - BACKGROUND: Three-dimensional contrast-enhanced MR pulmonary angiography (MRPA)
      is a suitable option for pulmonary embolism (PE) detection. However, there have
      been few reports on the diagnostic accuracy of MRPA for PE detection in a 3-T MR
      system. The purpose of this study was to evaluate the accuracy of MRPA in a 3-T
      MR system to detect acute PE with multidetector CT pulmonary angiography (CTPA)
      as reference standard. METHODS: Twenty-seven patients (18 males and 9 females,
      mean age 38.9+/-14.4 years) underwent both MRPA and CTPA within 3 days (range, 0
      3 days) for evaluating PE. Pulmonary emboli in MRPA were independently analyzed
      on a per-patient and per-lobe basis by two radiologists. CTPA was regarded as
      reference standard, which was evaluated by another two radiologists in consensus.
      Sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV), and accuracy for PE detection were calculated. Weighted kappa values
      were calculated to evaluate agreement between readers. RESULTS: Twenty-four
      patients had PE in 55 lung lobes in CTPA, while 3 patients had no PE detected.
      Readers 1 and 2 correctly detected 47 and 46 lung lobes having clots in 24 and 23
      patients, corresponding to sensitivities, specificities, PPV, NPV, and accuracies
      of 100%, 100%, 100%, 100%, 100%; 100%, 66.7%, 96.0%, 100%, 96.4% on a per-patient
      basis and 85.5%, 100%, 100%, 90.9%, 94.1%; 83.6%, 93.7%, 90.2%, 89.2%, 89.6% on a
      per-lobe basis; respectively. Excellent inter-reader agreement (kappa values=1.00
      and 0.934; both P<0.001) were found for detecting PE on a per-patient and per
      lobe analysis. CONCLUSION: Three-dimensional contrast-enhanced MRPA with a 3-T MR
      system is a suitable alternative modality to CTPA to detect PE on a per-patient
      basis based on this small cohort study.

PMID- 23958420
TI  - Hemoconcentration is a good prognostic predictor for clinical outcomes in acute
      heart failure: data from the Korean Heart Failure (KorHF) Registry.
AB  - BACKGROUND: Hemoconcentration is a surrogate marker of effective decongestion and
      diuresis therapy. Recently, hemoconcentration has been associated with decreased
      mortality and rehospitalization in heart failure (HF) patients. However, the
      prognostic power of hemoconcentration in a large sample-sized HF cohort was
      limited until now. METHODS AND RESULTS: We analyzed data from hospitalized
      patients with acute heart failure (AHF) that were enrolled in the Korean Heart
      Failure Registry(n=2,357). The primary end point was a composite of all-cause
      mortality and HF rehospitalization during the follow-up period (median=347,
      interquartile range=78-744 days).Hemoconcentration, defined as an increased
      hemoglobin level between admission and discharge, was presented in 1,016 AHF
      patients (43.1%). In multivariable logistic regression, hemoglobin, total
      cholesterol, and serum glucose levels at admission, and ischemic HF, were
      significant determinants for hemoconcentration occurrence. The Kaplan-Meier curve
      showed that event-free survival was significantly higher in the hemoconcentration
      group compared to the non-hemoconcentration group (65.1% vs. 58.1%, log rank
      p<0.001). In multiple Cox proportional hazard analysis, hemoconcentration was an
      independent predictor of the primary end point after adjusting for other HF risk
      factors (hazard ratio=0.671, 95% confidence interval=0.564-0.798, p<0.001).
      CONCLUSIONS: Hemoconcentration during hospitalization was a prognostic marker of
      fewer clinical events in the AHF cohort. Therefore, this novel surrogate marker
      will help in the risk stratification of AHF patients.

PMID- 23958421
TI  - Effects of direct infusion of bone marrow-derived progenitor cells and indirect
      mobilization of hematopoietic progenitor cells on atherosclerotic plaque and
      inflammatory process in atherosclerosis.
AB  - BACKGROUND: We sought to investigate the effects of lin-/sca+ cells, endothelial
      progenitor cells (EPCs) and granulocyte colony-stimulating factor (G-CSF)
      administration on atherosclerotic plaque progression. METHODS: Apolipoprotein E
      deficient (apoE(-/-)) mice were splenectomized and treated with high-cholesterol
      diet for 6 weeks in order to induce atherosclerotic plaque development. Bone
      marrow-derived Lin-/sca-1+ cells were isolated and further cultured to early
      growth endothelial progenitor cells (EPCs). Mice were divided in four groups
      (n=10/group) and received two intravenous injections of 5*10(5) cells (lin-/sca
      1+ or EPCs), or granulocyte colony-stimulating factor (G-CSF 100 MUg/kg/day) for
      7 days or normal saline. The same interventions were administered to animals,
      which had undergone unilateral hind-limb ischemia. Effects on inflammatory
      parameters, lesion severity, and atherosclerotic plaque area size were assessed.
      RESULTS: The administration of both G-CSF and progenitor cells significantly
      decreased the levels of IL-6, 6 weeks after the initiation of treatment.
      Atherosclerotic lesion area was reduced by G-CSF (atherosclerotic plaque area
      percentage 22.94%+/-3.68, p=0.001), by lin-/sca-1+ (23.27%+/-5.98, p=0.002) and
      cultured EPCs (23.16+/-4.86%, p=0.002) compared to control (32.75%+/-7.05). In
      the atherosclerotic mice that underwent limb ischemia, the atherosclerotic plaque
      area, was not significantly different between the treatment groups cultured EPCs
      treated mice and the control group (p=NS, for all). CONCLUSIONS: Direct infusion
      of progenitor cells and indirect mobilization of hematopoietic progenitor cells
      decreased plaque progression and levels of inflammatory molecules in a murine
      model of atherosclerosis. Treatment with G-CSF, lin-/sca-1+, or EPCs may exert
      beneficial effects on vascular inflammation and atherosclerotic plaque
      progression. However, the effects are diminished in an ischemic setting.

PMID- 23958422
TI  - Thirty years of clinical magnetocardiography at the Catholic University of Rome:
      diagnostic value and new perspectives for the treatment of cardiac arrhythmias.

PMID- 23958423
TI  - Respiratory function and functional capacity in Chagas cardiomyopathy.

PMID- 23958425
TI  - Scientific knowledge is possible with small-sample classification.
AB  - : A typical small-sample biomarker classification paper discriminates between
      types of pathology based on, say, 30,000 genes and a small labeled sample of less
      than 100 points. Some classification rule is used to design the classifier from
      this data, but we are given no good reason or conditions under which this
      algorithm should perform well. An error estimation rule is used to estimate the
      classification error on the population using the same data, but once again we are
      given no good reason or conditions under which this error estimator should
      produce a good estimate, and thus we do not know how well the classifier should
      be expected to perform. In fact, virtually, in all such papers the error estimate
      is expected to be highly inaccurate. In short, we are given no justification for
      any claims.Given the ubiquity of vacuous small-sample classification papers in
      the literature, one could easily conclude that scientific knowledge is impossible
      in small-sample settings. It is not that thousands of papers overtly claim that
      scientific knowledge is impossible in regard to their content; rather, it is that
      they utilize methods that preclude scientific knowledge. In this paper, we argue
      to the contrary that scientific knowledge in small-sample classification is
      possible provided there is sufficient prior knowledge. A natural way to proceed,
      discussed herein, is via a paradigm for pattern recognition in which we
      incorporate prior knowledge in the whole classification procedure (classifier
      design and error estimation), optimize each step of the procedure given available
      information, and obtain theoretical measures of performance for both classifiers
      and error estimators, the latter being the critical epistemological issue. In
      sum, we can achieve scientific validation for a proposed small-sample classifier
      and its error estimate. 

PMID- 23958424
TI  - Selective growth inhibition of human malignant melanoma cells by syringic acid
      derived proteasome inhibitors.
AB  - BACKGROUND: It has been shown that proteasome inhibition leads to growth arrest
      in the G1 phase of the cell cycle and/or induction of apoptosis. However, it was
      found that some of these inhibitors do not induce apoptosis in several human
      normal cell lines. This selective activity makes proteasome inhibition a
      promising target for new generation of anticancer drugs. Clinical validation of
      the proteasome, as a therapeutic target in oncology, has been provided by the
      dipeptide boronic acid derivative; bortezomib. Bortezomib has proven to be
      effective as a single agent in multiple myeloma and some forms of non-Hodgkin's
      lymphoma. Syringic acid (4-hydroxy-3,5-dimethoxybenzoic acid, 1), a known
      phenolic acid, was isolated from the methanol extract of Tamarix aucheriana and
      was shown to possess proteasome inhibitory activity. METHODS: Using Surflex-Dock
      program interfaced with SYBYL, the docking affinities of syringic acid and its
      proposed derivatives to 20S proteasome were studied. Several derivatives were
      virtually proposed, however, five derivatives: benzyl 4-hydroxy-3,5
      dimethoxybenzoate (2), benzyl 4-(benzyloxy)-3,5-dimethoxybenzoate (3), 3'
      methoxybenzyl 3,5-dimethoxy-4-(3'-methoxybenzyloxy)benzoate (4), 3'-methoxybenzyl
      4-hydroxy-3,5-dimethoxybenzoate (5) and 3',5'-dimethoxybenzyl 4-hydroxy-3,5
      dimethoxybenzoate (6), were selected based on high docking scores, synthesized,
      and tested for their anti-mitogenic activity against human colorectal, breast and
      malignant melanoma cells as well as normal human fibroblast cells. RESULTS:
      Derivatives 2, 5, and 6 showed selective dose-dependent anti-mitogenic effect
      against human malignant melanoma cell lines HTB66 and HTB68 with minimal
      cytotoxicity on colorectal and breast cancer cells as well as normal human
      fibroblast cells. Derivatives 2, 5 and 6 significantly (p <= 0.0001) inhibited
      the various proteasomal chymotrypsin, PGPH, and trypsin like activities. They
      growth arrested the growth of HTB66 cells at G1 and G2-phases. They also arrested
      the growth of HTB68 cells at S- and G2-phase, respectively. Moreover, derivatives
      2, 5, and 6 markedly induced apoptosis (>= 90%) in both HTB66 and HTB68.
      CONCLUSIONS: Computer-derived syringic acid derivatives possess selective anti
      mitogenic activity on human malignant melanoma cells that may be attributed to
      perturbation of cell cycle, induction of apoptosis and inhibition of various 26S
      proteasomal activities.

PMID- 23958426
TI  - Mitochondrial disruption occurs downstream from beta-adrenergic overactivation by
      isoproterenol in differentiated, but not undifferentiated H9c2 cardiomyoblasts:
      differential activation of stress and survival pathways.
AB  - beta-Adrenergic receptor stimulation plays an important role in cardiomyocyte
      stress responses, which may result in apoptosis and cardiovascular degeneration.
      We previously demonstrated that toxicity of the beta-adrenergic agonist
      isoproterenol on H9c2 cardiomyoblasts depends on the stage of cell
      differentiation. We now investigate beta-adrenergic receptor downstream signaling
      pathways and stress responses that explain the impact of muscle cell
      differentiation on hyper-beta-adrenergic stimulation-induced cytotoxicity. When
      incubated with isoproterenol, differentiated H9c2 muscle cells have increased
      cytosolic calcium, cyclic-adenosine monophosphate content and oxidative stress,
      as well as mitochondrial depolarization, increased superoxide anion, loss of
      subunits from the mitochondrial respiratory chain, decreased Bcl-xL content,
      increased p53 and phosphorylated-p66Shc as well as activated caspase-3.
      Undifferentiated H9c2 cells incubated with isoproterenol showed increased Bcl-xL
      protein and increased superoxide dismutase 2 which may act as protective
      mechanisms. We conclude that the differentiation of H9c2 is associated with
      differential regulation of stress responses, which impact the toxicity of several
      agents, namely those acting through beta-adrenergic receptors and resulting in
      mitochondrial disruption in differentiated cells only. 

PMID- 23958428
TI  - Impact of active and stable psoriasis on health-related quality of life: the PSO
      LIFE study.
AB  - INTRODUCTION AND OBJECTIVES: The aim of this study was to assess the impact of
      psoriasis on health-related quality of life (HRQOL) using different
      questionnaires. PATIENTS AND METHODS: Prospective observational study of patients
      with plaque psoriasis of at least 6 months' duration stratified by active and
      stable disease. The patients were evaluated at baseline, 7 days, and 12 weeks. At
      the 3 visits, the investigators recorded sociodemographic and clinical data and
      the patients completed the following HRQOL questionnaires: the Dermatology Life
      Quality Index (DLQI), the Psoriasis Disability Index (PDI), and psoriasis quality
      of life questionnaire (PSO-LIFE). RESULTS: In total, 304 patients (182 with
      active psoriasis and 122 with stable psoriasis) were evaluated. The mean (SD) age
      was 45.3 (14.5) years, and 56.3% of the group were men. At baseline, the mean
      (SD) psoriasis and area severity index (PASI) score was 17.0 (7.4) in patients
      with active disease and 5.6 (5.3) in those with stable disease; a reduction was
      seen in PASI scores during the evaluation period (P<.01). The mean (SD) score on
      the PSO-LIFE questionnaire increased significantly from 57.4 (20.4) to 72.2
      (19.6) in patients with active psoriasis and from 76.4 (20.6) to 82.3 (18.3) in
      those with stable disease (P<0.01 in both groups). The difference in standardized
      mean scores between the 2 groups was 0.79 for the DLQI, 0.62 for the PDI, and
      0.85 for the PSO-LIFE questionnaire. The impact of psoriasis on HRQOL as assessed
      by the PSO-LIFE questionnaire was greater in patients with lesions in visible
      areas than in those with less visible lesions (P<.01). Changes in PSO-LIFE and
      PASI scores were moderately and significantly correlated (r=-0.4). CONCLUSIONS:
      The impact of psoriasis on HRQOL is higher in patients with active disease. The
      PSO-LIFE questionnaire showed a greater tendency to discriminate between active
      and stable psoriasis than either the DLQI or the PDI. PSO-LIFE scores correlated
      significantly with lesion site and disease severity as measured by PASI.

PMID- 23958427
TI  - Cobalt stimulates HIF-1-dependent but inhibits HIF-2-dependent gene expression in
      liver cancer cells.
AB  - Hypoxia-inducible factors (HIFs) are transcriptional regulators that mediate the
      cellular response to low oxygen. Although HIF-1 is usually considered as the
      principal mediator of hypoxic adaptation, several tissues and different cell
      types express both HIF-1 and HIF-2 isoforms under hypoxia or when treated with
      hypoxia mimetic chemicals such as cobalt. However, the similarities or
      differences between HIF-1 and HIF-2, in terms of their tissue- and inducer
      specific activation and function, are not adequately characterized. To address
      this issue, we investigated the effects of true hypoxia and hypoxia mimetics on
      HIF-1 and HIF-2 induction and specific gene transcriptional activity in two
      hepatic cancer cell lines, Huh7 and HepG2. Both hypoxia and cobalt caused rapid
      induction of both HIF-1alpha and HIF-2alpha proteins. Hypoxia induced
      erythropoietin (EPO) expression and secretion in a HIF-2-dependent way.
      Surprisingly, however, EPO expression was not induced when cells were treated
      with cobalt. In agreement, both HIF-1- and HIF-2-dependent promoters (of PGK and
      SOD2 genes, respectively) were activated by hypoxia while cobalt only activated
      the HIF-1-dependent PGK promoter. Unlike cobalt, other hypoxia mimetics such as
      DFO and DMOG activated both types of promoters. Furthermore, cobalt impaired the
      hypoxic stimulation of HIF-2, but not HIF-1, activity and cobalt-induced HIF
      2alpha interacted poorly with USF-2, a HIF-2-specific co-activator. These data
      show that, despite similar induction of HIF-1alpha and HIF-2alpha protein
      expression, HIF-1 and HIF-2 specific gene activating functions respond
      differently to different stimuli and suggest the operation of oxygen-independent
      and gene- or tissue-specific regulatory mechanisms involving additional
      transcription factors or co-activators. 

PMID- 23958429
TI  - Marie Curie's contribution to Medical Physics.
AB  - On occasion of its 50th anniversary, the International Organization for Medical
      Physics (IOMP) from now on is going to celebrate annually an International Day of
      Medical Physics for which the 7th November, the birthday of Marie Sklodowska
      Curie, a most exceptional character in science at all and a pioneer of medical
      physics, has been chosen. This article briefly outlines her outstanding
      personality, sketches her fundamental discovery of radioactivity and emphasizes
      the impact of her various achievements on the development of medical physics at
      large. 

PMID- 23958430
TI  - A qualitative study: perceptions of the psychosocial consequences and access to
      support after an acute myocardial infarction.
AB  - OBJECTIVES: The aim of this study was to describe individuals' perceptions of the
      psychosocial consequences of an acute myocardial infarction (AMI) and of their
      access to support one year after the event. METHODS: The study included 20
      participants (14 men and six women) who lived in rural areas and had experienced
      their first AMI. Eleven were offered contact with a mentor. The participants were
      interviewed one year after their AMI. RESULTS: The findings are presented in
      three themes: having a different life, having to manage the situation and having
      access to support, with 11 subthemes. During their recovery, the participants
      experienced psychosocial consequences, consisting of anxiety and the fear of
      being afflicted again. Most mentees appreciated their mentor and some of those
      without mentors wished they had received organised support. Participants were
      often more dissatisfied than satisfied with the follow-up provided during
      recovery. CONCLUSIONS: After an AMI, follow-up is important during recovery, but
      the standardised information provided is inadequate. During recovery, people need
      help dealing with existential crises. After discharge, receiving peer support
      from lay people with similar experiences could be valuable. The knowledge gleaned
      from this study could be used in education at coronary care units and in health
      care outside the hospital setting.

PMID- 23958431
TI  - The experience of being a trauma nurse: a phenomenological study.
AB  - The lived experience of being a trauma nurse was explored using a
      phenomenological qualitative research approach. Seven registered nurses employed
      in a trauma unit from one large metropolitan Canadian teaching hospital
      participated in in-depth conversational interviews. Data analysis revealed four
      sub theme clusters embedded within the overarching theme of Seeing Through Cloudy
      Situations: being on guard all the time, being caught up short, facing the
      challenge and sharing the journey. Even though trauma nurses are able to find
      meaning and satisfaction in their work, the findings of this research reveal the
      need for support and the assurance of safe work environments as trauma nurses can
      live with violence and aggression in their daily nursing practice. 

PMID- 23958432
TI  - CT imaging with fistulography for perianal fistula: does it really help the
      surgeon?
AB  - OBJECTIVE: To prospectively evaluate the relative accuracy of computed tomography
      (CT) fistulography for preoperative assessment of fistula in ano. MATERIALS AND
      METHODS: Ethical committee approval and informed consent were obtained. A total
      of 22 patients (15 male and 7 female, age 21-58 years) who were suspected of
      having fistula in ano underwent preoperative CT fistulography (CTF). The CT
      images of 0.6 mm were obtained respectively before and after fistulography;
      contrast-enhanced CT scan was also performed in 22 patients. CTF images were
      evaluated by two expert radiologists to assess the fistulas in the following
      respects: (a) the volume-rendered imaging; (b) the extensions of active
      inflammatory tissue; (c) the internal opening and external opening; (d) the
      hidden areas of tract or abscess; and (e) the deep abscess adjacent to fistula.
      CT findings in 18 patients were compared with surgical findings or exam under
      anesthesia. RESULTS: The CTF findings in 18 cases were basically in accordance
      with the surgical findings and/or examination findings under anesthesia. Both
      coronal and transverse planes were useful in assessing the location and direction
      of tracts or abscesses. Complicated spatial information within the perianal soft
      tissue about the fistula with secondary ramifications or abscesses can be easily
      demonstrated to the surgeons. Contrast-enhanced images were useful in assessing
      the inflammatory lesion activity and infiltrated area. CONCLUSION: CTF
      exquisitely depicts the perianal anatomy and shows the fistulous tracks with
      their associated ramifications, enables selection of the most appropriate
      surgical treatment, and therefore minimizes all chances of recurrence.

PMID- 23958433
TI  - Clinical significance of NUCB2 mRNA expression in prostate cancer.
AB  - BACKGROUND: Nucleobindin 2 (NUCB2) abnormal expression has been reported in
      gastric cancer and breast cancer. However, the role of NUCB2 in prostate cancer
      (PCa) remains unclear. The aim of the present study was to investigate the NUCB2
      expression in PCa tissues and adjacent non-cancerous tissues and its potential
      relevance to clinicopathological variables and prognosis. METHODS: NUCB2 mRNA
      expression was determined by real-time quantitative real time reverse
      transcriptase polymerase chain reaction in 180 pairs of fresh frozen PCa tissues
      and corresponding non-cancerous tissues. Kaplan-Meier analysis and Cox
      proportional hazards regression models were used to investigate the correlation
      between NUCB2 expression and prognosis of PCa patients. RESULTS: Our results
      showed that the expression level of NUCB2 mRNA in PCa tissues was significantly
      higher than those in non-cancerous tissues. Our results indicated that the high
      expression of NUCB2 in PCa was associated with lymph node metastasis,
      preoperative PSA, Gleason score, and angiolymphatic invasion. Kaplan-Meier
      survival analysis showed that patients with high NUCB2 expression have shorter
      biochemical recurrence (BCR)-free survival time compared to patients with low
      NUCB2 expression. Multivariate analysis revealed that NUCB2 expression was an
      independent predictor of BCR-free survival. CONCLUSIONS: NUCB2 might play a
      positive role in PCa development and could serve as an independent predictor of
      BCR-free survival.

PMID- 23958434
TI  - The correlation between self-reported and measured height, weight, and BMI in
      reproductive age women.
AB  - This prospective, cross-sectional study of 60 women compares self-reported
      height, weight, and BMI with measured values. Self-reported BMI (29.0+/-8.37
      kg/m(2)) was slightly lower than measured BMI (29.1+/-8.38 kg/m(2)) (p=0.4).
      Eighty percent of participants reported a BMI in the same category in which their
      BMI was measured. Pearson's correlation coefficient for height (0.96, p<0.001),
      weight (0.99, p<0.001), and BMI (0.99, p<0.001) were high. Reproductive age women
      accurately reported their height and weight.

PMID- 23958435
TI  - Malnutrition in the elderly: a narrative review.
AB  - The focus of nutrition is often on healthy diets and exercise to minimise the
      risk of developing lifestyle diseases such as cancer, diabetes and cardiovascular
      disease. However, during the shift into older years often the nutrition
      priorities change towards meeting increased nutrient needs with less energy
      requirements, and minimising lean muscle loss. There are several causes of
      general malnutrition in the elderly that lead to depletion of muscle including
      starvation (protein-energy malnutrition), sarcopenia and cachexia. The prevalence
      of protein-energy malnutrition increases with age and the number of
      comorbidities. A range of simple and validated screening tools can be used to
      identify malnutrition in older adults, e.g. MST, MNA-SF and 'MUST'. Older adults
      should be screened for nutritional issues at diagnosis, on admission to hospitals
      or care homes and during follow up at outpatient or General Practitioner clinics,
      at regular intervals depending on clinical status. Early identification and
      treatment of nutrition problems can lead to improved outcomes and better quality
      of life. 

PMID- 23958437
TI  - Loss of Xenopus cadherin-11 leads to increased Wnt/beta-catenin signaling and up
      regulation of target genes c-myc and cyclin D1 in neural crest.
AB  - Xenopus cadherin-11 (Xcadherin-11) is an exceptional cadherin family member,
      which is predominantly expressed in cranial neural crest cells (NCCs). Apart from
      mediating cell-cell adhesion it promotes cranial NCC migration by initiating
      filopodia and lamellipodia formation. Here, we demonstrate an unexpected function
      of Xcadherin-11 in NCC specification by interfering with canonical Wnt/beta
      catenin signaling. Loss-of-function experiments, using a specific antisense
      morpholino oligonucleotide against Xcadherin-11, display a nuclear beta-catenin
      localization in cranial NCCs and a broader expression domain of the proto
      oncogene cyclin D1 which proceeds c-myc up-regulation. Additionally, we observe
      an enhanced NCC proliferation and an expansion of specific NCC genes like AP2 and
      Sox10. Thereby, we could allocate NCC proliferation and specification to
      different gene functions. To clarify which domain in Xcadherin-11 is required for
      early NCC development we tested different deletion mutants for their rescue
      ability in Xcadherin-11 morphants. We identified the cytoplasmic tail,
      specifically the beta-catenin binding domain, to be necessary for proper NCC
      development. We propose that Xcadherin-11 is necessary for controlled NCC
      proliferation and early NCC specification in tuning the expression of the
      canonical Wnt/beta-catenin target genes cyclin D1 and c-myc by regulating the
      concentration of the nuclear pool of beta-catenin. 

PMID- 23958436
TI  - Enteric neural crest-derived cells promote their migration by modifying their
      microenvironment through tenascin-C production.
AB  - The enteric nervous system (ENS) is derived from vagal and sacral neural crest
      cells that migrate, proliferate, and differentiate into enteric neurons and glia
      within the gut wall. The mechanisms regulating enteric neural crest-derived cell
      (ENCC) migration are poorly characterized despite the importance of this process
      in gut formation and function. Characterization of genes involved in ENCC
      migration is essential to understand ENS development and could provide targets
      for treatment of human ENS disorders. We identified the extracellular matrix
      glycoprotein tenascin-C (TNC) as an important regulator of ENCC development. We
      find TNC dynamically expressed during avian gut development. It is absent from
      the cecal region just prior to ENCC arrival, but becomes strongly expressed
      around ENCCs as they enter the ceca and hindgut. In aganglionic hindguts, TNC
      expression is strong throughout the outer mesenchyme, but is absent from the
      submucosal region, supporting the presence of both ENCC-dependent and independent
      expression within the gut wall. Using rat-chick coelomic grafts, neural tube
      cultures, and gut explants, we show that ENCCs produce TNC and that this ECM
      protein promotes their migration. Interestingly, only vagal neural crest-derived
      ENCCs express TNC, whereas sacral neural crest-derived cells do not. These
      results demonstrate that vagal crest-derived ENCCs actively modify their
      microenvironment through TNC expression and thereby help to regulate their own
      migration. 

PMID- 23958438
TI  - Mitochondrial quality control in neurodegenerative diseases.
AB  - Mutations causing genetic forms of Parkinson's disease or hereditary neuropathies
      have been recently shown to affect key molecular players involved in the
      recycling of defective mitochondria, most notably PARKIN, PINK1, Mitofusin 2 or
      dynein heavy chain. Interestingly, the same pathways are also indirectly targeted
      by multiple other mutations involved in familial forms of amyotrophic lateral
      sclerosis, Huntington's disease or Alzheimer's disease. These recent genetic
      results strongly reinforce the notion that defective mitochondrial physiology
      might cause neurodegeneration. Mitochondrial dysfunction has however been
      observed in virtually every neurodegenerative disease and appears not restricted
      to the most vulnerable neuronal populations affected by a given disease. Thus,
      the mechanisms linking defective mitochondrial quality control to death of
      selective neuronal populations remain to be identified. This review provides an
      update on the most recent literature on mitochondrial quality control and its
      impairment during neurodegenerative diseases. 

PMID- 23958439
TI  - From fatty-acid sensing to chylomicron synthesis: role of intestinal lipid
      binding proteins.
AB  - Today, it is well established that the development of obesity and associated
      diseases results, in part, from excessive lipid intake associated with a
      qualitative imbalance. Among the organs involved in lipid homeostasis, the small
      intestine is the least studied even though it determines lipid bioavailability
      and largely contributes to the regulation of postprandial hyperlipemia
      (triacylglycerols (TG) and free fatty acids (FFA)). Several Lipid-Binding
      Proteins (LBP) are expressed in the small intestine. Their supposed intestinal
      functions were initially based on what was reported in other tissues, and took no
      account of the physiological specificity of the small intestine. Progressively,
      the identification of regulating factors of intestinal LBP and the description of
      the phenotype of their deletion have provided new insights into cellular and
      molecular mechanisms involved in fat absorption. This review will discuss the
      physiological contribution of each LBP in the main steps of intestinal absorption
      of long-chain fatty acids (LCFA): uptake, trafficking and reassembly into
      chylomicrons (CM). Moreover, current data indicate that the small intestine is
      able to adapt its lipid absorption capacity to the fat content of the diet,
      especially through the coordinated induction of LBP. This adaptation requires the
      existence of a mechanism of intestinal lipid sensing. Emerging data suggest that
      the membrane LBP CD36 may operate as a lipid receptor that triggers an
      intracellular signal leading to the modulation of the expression of LBP involved
      in CM formation. This event could be the starting point for the optimized
      synthesis of large CM, which are efficiently degraded in blood. Better
      understanding of this intestinal lipid sensing might provide new approaches to
      decrease the prevalence of postprandial hypertriglyceridemia, which is associated
      with cardiovascular diseases, insulin resistance and obesity. 

PMID- 23958440
TI  - Biological evidence for the world's smallest tRNAs.
AB  - Due to their function as adapters in translation, tRNA molecules share a common
      structural organization in all kingdoms and organelles with ribosomal protein
      biosynthesis. A typical tRNA has a cloverleaf-like secondary structure,
      consisting of acceptor stem, D-arm, anticodon arm, a variable region, and T-arm,
      with an average length of 73 nucleotides. In several mitochondrial genomes,
      however, tRNA genes encode transcripts that show a considerable deviation of this
      standard, having reduced D- or T-arms or even completely lack one of these
      elements, resulting in tRNAs as small as 66 nts. An extreme case of such
      truncations is found in the mitochondria of Enoplea. Here, several tRNA genes are
      annotated that lack both the D- and the T-arm, suggesting even shorter
      transcripts with a length of only 42 nts. However, direct evidence for these
      exceptional tRNAs, which were predicted by purely computational means, has been
      lacking so far. Here, we demonstrate that several of these miniaturized armless
      tRNAs consisting only of acceptor- and anticodon-arms are indeed transcribed and
      correctly processed by non-encoded CCA addition in the mermithid Romanomermis
      culicivorax. This is the first direct evidence for the existence and
      functionality of the smallest tRNAs ever identified so far. It opens new
      possibilities towards exploration/assessment of minimal structural motifs
      defining a functional tRNA and their evolution. 

PMID- 23958441
TI  - Trends of PCDD/F and PCB concentrations and depositions in ambient air in
      Northwestern Germany.
AB  - Time series of polychlorinated dioxins and furans (PCDD/F) and polychlorinated
      biphenyls (PCB) in ambient air of a large conurbation in North-Western Germany
      are presented and analyzed. The trend of PCDD/F concentrations, starting from as
      early as 1988, shows a pronounced decrease by at least one order of magnitude,
      demonstrating that the emission reductions were effective. The PCDD/F depositions
      also have decreased by a factor of 5 since 1992. However, both trends have
      leveled out since 2005. Time series of PCB concentrations and depositions
      starting in 1994 show only slight decreases for the concentrations and almost no
      decrease for the depositions. From the decay rates following first order
      kinetics, half-lives in the order of 5-15 years for the PCDD/F and 15-31 years
      for the sum of the six indicator PCB could be calculated, which are much longer
      than the half-lives estimated from their reactivity towards the OH radical.
      Apparently, small fresh emissions (PCDD/F), considerable secondary emissions and
      evaporation from contaminated soils slow down their decay in the atmosphere of
      big conurbations. Analyzing the decay rates of individual PCB congeners shows
      that the lower chlorinated and more volatile ones are removed faster than the
      higher chlorinated congeners, probably via gas phase reactions with the OH
      radical. It can be concluded from the present study that the input of PCDD/F and
      PCB into the food chain via the air path will continue for another one or two
      decades in big conurbations.

PMID- 23958442
TI  - The utility of behavioral studies for aquatic toxicology testing: a meta
      analysis.
AB  - Behavioral responses have been applied for decades as tools for aquatic toxicity
      testing, but have received far less attention than studies assessing lethality,
      development or reproduction. With improved visual and non-visual assessment tools
      and increased knowledge of the importance of behavior for organism health and
      fitness, interest in behavioral analysis has increased in recent years. However,
      to our knowledge there has never been a quantitative assessment of the available
      techniques for organismal toxicity testing, so it is not clear whether behavioral
      studies represent valuable additions to environmental monitoring. We performed a
      meta-analysis comparing the relative sensitivities and average durations of
      behavioral studies to those assessing acute lethality, development and
      reproduction. Results demonstrate that the average duration of behavioral studies
      is consistently less than developmental or reproductive studies, and that
      behavioral endpoints are generally more sensitive than those assessing
      development or reproduction. We found effect sizes to be lower but power to be
      higher in behavioral and reproductive studies compared to studies assessing
      development, which likely relates to low sample sizes commonly used in
      developmental studies. Overall, we conclude that behavioral studies are
      comparatively fast and sensitive, and therefore warrant further attention as
      tools for assessing the toxicological effects of environmental contaminants. We
      suggest that research aimed at developing and optimizing techniques for
      behavioral analysis could prove extremely useful to the field of toxicology, but
      that future work must be directed at determining what specific behaviors are most
      sensitive to various classes of contaminants, and at understanding the relevance
      of changes to discrete behaviors for influencing organismal and population-level
      health and fitness. 

PMID- 23958443
TI  - Effects of environmental conditions on the release of phosphorus from biochar.
AB  - Biochar, the byproduct from fast pyrolysis of waste biomass, is widely used as a
      soil conditioner. The phosphorus in biochar is not only a P source for plant
      growth, but also an important factor caused the eutrophication of water. Here,
      the effects of environmental conditions on the release of different P species
      from biochar in a biochar-water system were investigated. About 2.2 mg g(-1) P in
      the form of inorganic orthophosphate and pyrophosphate was released from a raw
      biochar (contained 4.7 mg P g(-1)) at initial pH of 9.0 in the initial 8h. The
      release of orthophosphate was significantly enhanced from 0.64 to 1.35 mg g(-1)
      by the coexisting anions of Cl(-), NO3(-) or SO4(2-) due to the effect of ion
      exchange competition, while the release of pyrophosphate (P2O7(4-)) was not
      influenced by the introduction of anions which might be attributed to the
      formation of stable complexes. The introduction of Hoagland nutrient solution led
      to the decrease in release of P due to the formation of precipitates between
      dissolved P and excessive Ca(2+) and Mg(2+).

PMID- 23958444
TI  - Algae mediate submerged macrophyte response to nutrient and dissolved inorganic
      carbon loading: a mesocosm study on different species.
AB  - Nutrient and dissolved inorganic carbon are two important factors that influence
      the development and species composition of submerged macrophyte communities in
      shallow lake ecosystems. Yet little is known about their potential interactive
      effects on the submerged macrophytes and competition outcome of macrophyte
      phytoplankton. We performed a mesocosm experiment to investigate the growth and
      photosynthetic performance of three submerged macrophytes in relation to
      phytoplankton/epiphyton with nutrient and bicarbonate enrichment. During the
      experimental period (42 d), increase in nutrient loading in water column resulted
      in a substantial burst of phytoplankton and epiphyton growth and increased light
      attenuation. When combined with nutrient loading, bicarbonate enrichment also
      resulted in a heavily phytoplankton- and epiphyton-dominated state, although
      bicarbonate enrichment per se does not cause the phytoplankton and epiphyton
      growth. However, increase in nutrient loading in water column had significant
      negative impact on individual performances (growth and photosynthesis) of the
      three submerged macrophytes and bicarbonate enrichment increased the effect of
      eutrophication on two dissected-leaf macrophytes (M. spicatum and E. nuttallii).
      Furthermore, our results also suggest that species-specific photosynthetic
      performances occurred when submerged macrophytes in an environment with high
      abundance of phytoplankton/epiphyton. This study highlighted that increase in
      nutrient loading and bicarbonate in water column is likely to interactively
      impact both abiotic and biotic properties of a freshwater ecosystem. The
      interactions of these two factors could select macrophyte species that are able
      to resist the shading from phytoplankton/epiphyton, making these species more
      dominant in natural freshwater ecosystems. 

PMID- 23958445
TI  - A two-way street: bridging implementation science and cultural adaptations of
      mental health treatments.
AB  - BACKGROUND: Racial and ethnic disparities in the United States exist along the
      entire continuum of mental health care, from access and use of services to the
      quality and outcomes of care. Efforts to address these inequities in mental
      health care have focused on adapting evidence-based treatments to clients'
      diverse cultural backgrounds. Yet, like many evidence-based treatments,
      culturally adapted interventions remain largely unused in usual care settings. We
      propose that a viable avenue to address this critical question is to create a
      dialogue between the fields of implementation science and cultural adaptation. In
      this paper, we discuss how integrating these two fields can make significant
      contributions to reducing racial and ethnic disparities in mental health care.
      DISCUSSION: The use of cultural adaptation models in implementation science can
      deepen the explicit attention to culture, particularly at the client and provider
      levels, in implementation studies making evidence-based treatments more
      responsive to the needs and preferences of diverse populations. The integration
      of both fields can help clarify and specify what to adapt in order to achieve
      optimal balance between adaptation and fidelity, and address important
      implementation outcomes (e.g., acceptability, appropriateness). A dialogue
      between both fields can help clarify the knowledge, skills and roles of who
      should facilitate the process of implementation, particularly when cultural
      adaptations are needed. The ecological perspective of implementation science
      provides an expanded lens to examine how contextual factors impact how treatments
      (adapted or not) are ultimately used and sustained in usual care settings.
      Integrating both fields can also help specify when in the implementation process
      adaptations may be considered in order to enhance the adoption and sustainability
      of evidence-based treatments. SUMMARY: Implementation science and cultural
      adaptation bring valuable insights and methods to how and to what extent
      treatments and/or context should be customized to enhance the implementation of
      evidence-based treatments across settings and populations. Developing a two-way
      street between these two fields can provide a better avenue for moving the best
      available treatments into practice and for helping to reduce racial and ethnic
      disparities in mental health care.

PMID- 23958446
TI  - Differential effects of modafinil on memory in naive and memory-impaired rats.
AB  - Modafinil is a wake-promoting drug and has been approved for the treatment of
      excessive daytime sleepiness in narcolepsy and obstructive sleep apnea. Modafinil
      was shown to improve learning and memory in rodents, and to reverse memory
      deficits induced by sleep deprivation or stress. However, depending on the memory
      paradigm used, modafinil might also impair memory. We aimed to investigate the
      effects of modafinil on memory consolidation and retrieval for object recognition
      and inhibitory avoidance in naive adult rats. We also investigated whether acute
      or chronic administration of modafinil would reverse memory deficits induced by
      iron overload, a model of memory impairment related to neurodegenerative
      disorders. Adult naive rats received modafinil (0.0, 0.75, 7.5 or 75 mg/kg)
      either immediately after training or 1 h prior to testing in object recognition
      or inhibitory avoidance. Iron-treated rats received modafinil immediately after
      training in object recognition. In order to investigate the effects of chronic
      modafinil, iron-treated rats received daily injections of modafinil for 17 days,
      and 24 h later they were trained in object recognition or inhibitory avoidance.
      Acute modafinil does not affect memory consolidation or retrieval in naive rats.
      A single injection of modafinil at the highest dose was able to recover
      recognition memory in iron-treated rats. Chronic modafinil completely recovered
      iron-induced recognition memory and emotional memory deficits. Additional
      preclinical and clinical studies are necessary in order to support the
      applicability of modafinil in recovering memory impairment associated with
      neurodegenerative disorders. 

PMID- 23958447
TI  - Cathepsin X promotes 6-hydroxydopamine-induced apoptosis of PC12 and SH-SY5Y
      cells.
AB  - The cysteine carboxypeptidase cathepsin X is an important player in degenerative
      processes under normal ageing and pathological conditions. In the present study,
      we investigated the potential role of cathepsin X in 6-hydroxydopamine (6-OHDA)
      induced toxicity in the pheochromocytoma cell line PC12 and neuroblastoma cell
      line SH-SY5Y. Cells exposed to 6-OHDA demonstrated alterations in the protein
      level of cathepsin X and activity of cathepsin X. Downregulation of cathepsin X
      expression by siRNA attenuated the neuronal death caused by 6-OHDA. Treatment
      with specific cathepsin X inhibitor AMS36 protected cells against 6-OHDA mediated
      cytotoxicity, resulting in reduced cell death and apoptosis. Furthermore, AMS36
      reversed 6-OHDA-induced loss of tyrosine hydroxylase and attenuated 6-OHDA
      induced activation of caspase-3, triggering apoptosis, intracellular generation
      of reactive oxygen species and mitochondrial dysfunction, including the release
      of cytochrome c and an imbalanced Bax/Bcl-2 ratio. Moreover, AMS36 interfered
      with NF-kappaB activation by blocking degradation of IkappaBalpha, preventing NF
      kappaB translocation to the nucleus. Our data provide the first evidence that
      inhibition of cathepsin X protects both, PC12 and SH-SY5Y cells against 6-OHDA
      toxicity and indicate that cathepsin X may be responsible for dopamine neuron
      death, involved in the pathogenic cascade event for the neurodegenerative
      disorders, such as Parkinson's disease.

PMID- 23958449
TI  - Exogenous BDNF facilitates strategy set-shifting by modulating glutamate dynamics
      in the dorsal striatum.
AB  - Brain-derived neurotrophic factor (BDNF) signaling via tropomyosin-related kinase
      B (trkB) receptors exerts modulatory effects on glutamatergic transmission,
      learning, memory and reward processing. Although the role of BDNF in the
      regulation of mnemonic and affective/motivational processes is well studied,
      whether this neurotrophin could also regulate executive functions is not known.
      In the present study, we assessed the effects of intrastriatal infusions on BDNF
      (1-100 ng/hemisphere) in mice performing an operant strategy set-shifting task
      that required the animals to eliminate a visual cue-based strategy and adopt a
      new egocentric spatial response strategy to achieve rewards. Exogenous BDNF
      administration facilitated the acquisition of strategy shifting by minimizing
      response perseveration to the previously acquired strategy and this effect
      resemble an inverted-U shaped dose-response pattern. Faster acquisition of
      strategy switching in BDNF-infused animals was dependent upon the activation of
      striatal trkB receptors. Moreover, activation of mGluR2/3 receptors by the
      selective group II metabotropic receptor agonist LY379268 abolished BDNF-induced
      cognitive enhancement suggesting the involvement of presynaptic glutamatergic
      activity. Assessment of striatal glutamate dynamics using electrochemical
      recordings indicated that local application of BDNF directly induces glutamate
      release by activating presynaptic trkB receptors on glutamatergic terminals, and
      this effect followed a bell-shaped dose-response pattern similar to strategy
      shifting performance. These data suggest that activation of BDNF-trkB signaling
      in the dorsal striatum improves strategy switching by effectively minimizing
      response conflicts, and this effect primarily involves facilitation of
      glutamatergic transmission. 

PMID- 23958448
TI  - Active DNA demethylation in post-mitotic neurons: a reason for optimism.
AB  - Over the last several years proteins involved in base excision repair (BER) have
      been implicated in active DNA demethylation. We review the literature supporting
      BER as a means of active DNA demethylation, and explain how the various
      components function and cooperate to remove the potentially most enduring means
      of epigenetic gene regulation. Recent evidence indicates that the same pathways
      implicated during periods of widespread DNA demethylation, such as the erasure of
      methyl marks in the paternal pronucleus soon after fertilization, are operational
      in post-mitotic neurons. Neuronal functional identities, defined here as the
      result of a combination of neuronal subtype, location, and synaptic connections
      are largely maintained through DNA methylation. Chronic mental illnesses, such as
      schizophrenia, may be the result of both altered neurotransmitter levels and
      neurons that have assumed dysfunctional neuronal identities. A limitation of most
      current psychopharmacological agents is their focus on the former, while not
      addressing the more profound latter pathophysiological process. Previously, it
      was believed that active DNA demethylation in post-mitotic neurons was rare if
      not impossible. If this were the case, then reversing the factors that maintain
      neuronal identity, would be highly unlikely. The emergence of an active DNA
      demethylation pathway in the brain is a reason for great optimism in psychiatry
      as it provides a means by which previously pathological neurons may be
      reprogrammed to serve a more favorable role. Agents targeting epigenetic
      processes have shown much promise in this regard, and may lead to substantial
      gains over traditional pharmacological approaches. 

PMID- 23958450
TI  - Monitoring cholinergic activity during attentional performance in mice
      heterozygous for the choline transporter: a model of cholinergic capacity limits.
AB  - Reductions in the capacity of the human choline transporter (SLC5A7, CHT) have
      been hypothesized to diminish cortical cholinergic neurotransmission, leading to
      risk for cognitive and mood disorders. To determine the acetylcholine (ACh)
      release capacity of cortical cholinergic projections in a mouse model of
      cholinergic hypofunction, the CHT+/- mouse, we assessed extracellular ACh levels
      while mice performed an operant sustained attention task (SAT). We found that
      whereas SAT-performance-associated increases in extracellular ACh levels of CHT+/
      mice were significantly attenuated relative to wildtype littermates, performance
      on the SAT was normal. Tetrodotoxin-induced blockade of neuronal excitability
      reduced both dialysate ACh levels and SAT performance similarly in both
      genotypes. Likewise, lesions of cholinergic neurons abolished SAT performance in
      both genotypes. However, cholinergic activation remained more vulnerable to the
      reverse-dialyzed muscarinic antagonist atropine in CHT+/- mice. Additionally,
      CHT+/- mice displayed greater SAT-disrupting effects of reverse dialysis of the
      nAChR antagonist mecamylamine. Receptor binding assays revealed a higher density
      of alpha4beta2* nAChRs in the cortex of CHT+/- mice compared to controls. These
      findings reveal compensatory mechanisms that, in the context of moderate
      cognitive challenges, can overcome the performance deficits expected from the
      significantly reduced ACh capacity of CHT+/- cholinergic terminals. Further
      analyses of molecular and functional compensations in the CHT+/- model may
      provide insights into both risk and resiliency factors involved in cognitive and
      mood disorders. 

PMID- 23958451
TI  - Three Ca2+ channel inhibitors in combination limit chronic secondary degeneration
      following neurotrauma.
AB  - Following neurotrauma, cells beyond the initial trauma site undergo secondary
      degeneration, with excess Ca2+ a likely trigger for loss of neurons, compact
      myelin and function. Treatment using inhibitors of specific Ca2+ channels has
      shown promise in preclinical studies, but clinical trials have been disappointing
      and combinatorial approaches are needed. We assessed efficacy of multiple
      combinations of three Ca2+ channel inhibitors at reducing secondary degeneration
      following partial optic nerve transection in rat. We used lomerizine to inhibit
      voltage gated Ca2+ channels; oxidised adenosine-triphosphate (oxATP) to inhibit
      purinergic P2X7 receptors and/or 2-[7-(1H-imidazol-1-yl)-6-nitro-2,3-dioxo
      1,2,3,4-tetrahydro quinoxalin-1-yl]acetic acid (INQ) to inhibit Ca2+ permeable
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Only
      the three Ca2+ channel inhibitors delivered in combination significantly
      preserved visual function, as assessed using the optokinetic nystagmus visual
      reflex, at 3 months after injury. Preservation of retinal ganglion cells was
      partial and is unlikely to have accounted for differential effects on function. A
      range of the Ca2+ channel inhibitor combinations prevented swelling of optic
      nerve vulnerable to secondary degeneration. Each of the treatments involving
      lomerizine significantly increased the proportion of axons with normal compact
      myelin. Nevertheless, limiting decompaction of myelin was not sufficient for
      preservation of function in our model. Multiple combinations of Ca2+ channel
      inhibitors reduced formation of atypical node/paranode complexes; outcomes were
      not associated with preservation of visual function. However, prevention of
      lengthening of the paranodal gap that was only achieved by treatment with the
      three Ca2+ channel inhibitors in combination was an important additional effect
      that likely contributed to the associated preservation of the optokinetic reflex
      using this combinatorial treatment strategy.

PMID- 23958453
TI  - The promises and perils of hospital autonomy: reform by decree in Viet Nam.
AB  - This article investigates impacts of hospital autonomization in Viet Nam
      employing a "decision-space" framework that examines how hospitals have used
      their increased discretion and to what effect. Analysis suggests autonomization
      is associated with increased revenue, increasing staff pay, and greater
      investment in infrastructure and equipment. But autonomization is also associated
      with more costly and intensive treatment methods of uncertain contribution to the
      Vietnamese government's stated goal of quality healthcare for all. Impacts of
      autonomization in district hospitals are less striking. Despite certain
      limitations, the analysis generates key insights into early stages of hospital
      autonomization in Viet Nam. 

PMID- 23958452
TI  - CCL5-glutamate interaction in central nervous system: Early and acute presynaptic
      defects in EAE mice.
AB  - We investigated the CCL5-glutamate interaction in the cortex and in the spinal
      cord from mice with Experimental Autoimmune Encephalomyelitis (EAE) at 13 and
      21/30 days post immunization (d.p.i.), representing the onset and the peak of the
      disease, respectively. An early reduction of the KCl-evoked glutamate release was
      observed in cortical terminals from EAE mice at 13 d.p.i., persisting until 21/30
      d.p.i. A concomitant reduction of the depolarization-evoked cyclic adenosine
      monophosphate (cAMP), but not of the inositol 1,4,5-trisphosphate (IP3) cortical
      production also occurred at 13 d.p.i, that still was detectable at the acute
      stage of disease (21 dp.i.). Inasmuch, the CCL5-mediated inhibition of glutamate
      exocytosis observed in control mice turned to facilitation in EAE mouse cortex at
      13 d.p.i., then becoming undetectable at 21/30 d.p.i. Differently, glutamate
      exocytosis, as well as IP3 and cAMP productions were unaltered in spinal cord
      synaptosomes from EAE mice at 13 d.p.i., but significantly increased at 21/30
      d.p.i., while the presynaptic CCL5-mediated facilitation of glutamate exocytosis
      observed in control mice remained unchanged. In both CNS regions, the presynaptic
      defects were parallelled by increased CCL5 availability. Inasmuch, the
      presynaptic defects so far described in EAE mice were reminiscent of the effects
      acute CCL5 exerts in control conditions. Based on these observations we propose
      that increased CCL5 bioavailability could have a role in determining the
      abovedescribed impaired presynaptic impairments in both CNS regions. These
      presynaptic defects could be relevant to the onset of early cognitive impairments
      and acute neuroinflammation and demyelinating processes observed in multiple
      sclerosis patients. 

PMID- 23958454
TI  - Anopheles culicifacies breeding in polluted water bodies in Trincomalee District
      of Sri Lanka.
AB  - BACKGROUND: Anopheles culicifacies, the major vector of malaria in Sri Lanka, is
      known to breed in clean and clear water. The main objective of the study was to
      detect the breeding habitat diversity of An. culicifacies. METHODS: Potential
      larval habitats for Anopheles mosquitoes were surveyed on a monthly basis for 17
      months (January 2011-June 2012) in four different selected sampling sites
      (Murthankulam, Kommnaimottai, Paranamadawachchiya and Kokmotawewa) in Trincomalee
      District of Sri Lanka. RESULTS: A total of 2,996 larval specimens representing 13
      Anopheles species were reported from 16 different breeding habitats. According to
      density criterion, An. culicifacies, Anopheles subpictus, Anopheles barbirostris,
      Anopheles peditaeniatus and Anopheles nigerrimus were dominant. Anopheles
      nigerrimus, An. subpictus and An. peditaeniatus were observed as constant in
      relation to their distribution. The most productive breeding site for An.
      culicifacies was drains filled with waste water in remote areas; the second
      highest productivity was found in built wells. CONCLUSIONS: These results
      indicate that An. culicifacies has adapted to breed in a wide range of water
      bodies including waste water collections although they were earlier considered to
      breed only in clean and clear water.

PMID- 23958455
TI  - Open innovation and intellectual property: time for a reboot?

PMID- 23958456
TI  - Factors influencing the demand of the service of community based animal health
      care in Zimbabwe.
AB  - This study was done to find out about animal health service providers and factors
      that determined demand for community based veterinary service delivery in
      smallholder sector of Zimbabwe. Focus group discussions and a questionnaire was
      used to collect data on veterinary services providers and socio-economic factors
      related to animal health from a sample (N=333) smallholder livestock farmers from
      Gutu district of Masvingo province in Zimbabwe. Analytical techniques used were
      descriptive statistics, K-mean cluster analysis and Tobit regression model.
      Results showed that the majority of farmers (45%) obtained services from both
      Community Based Animal Health Workers (CBAHWs) and Department of Veterinary
      Service (DVS), 25% DVS only, 20% used CBAHWs while 10% did not seek any services.
      Further analysis showed that distance to CBAHW, distance to AHMC and employment
      status were significantly related to demand for CBAHWs with coefficients of -1.5,
      0.7 and -10.3, respectively. The study thus concluded that CBAHW is an
      alternative animal health service delivery approach already practiced in
      smallholder farming sectors of Zimbabwe. Socio-economic factors significantly
      influenced the demand for CBAHW services. Given limited resources by state
      sponsored veterinary services, it is recommended that the CBAHWs approach should
      be encouraged as supplementary service provider especially in areas further DVS.
      These community organizations can be empowered by the state to deliver more
      improved services based on hygiene and modern science at a relatively low cost to
      farmers. 

PMID- 23958457
TI  - The economic impacts of foot and mouth disease - what are they, how big are they
      and where do they occur?
AB  - Although a disease of low mortality, the global impact of foot and mouth disease
      (FMD) is colossal due to the huge numbers of animals affected. This impact can be
      separated into two components: (1) direct losses due to reduced production and
      changes in herd structure; and (2) indirect losses caused by costs of FMD
      control, poor access to markets and limited use of improved production
      technologies. This paper estimates that annual impact of FMD in terms of visible
      production losses and vaccination in endemic regions alone amount to between
      US$6.5 and 21 billion. In addition, outbreaks in FMD free countries and zones
      cause losses of >US$1.5 billion a year. FMD impacts are not the same throughout
      the world: FMD is highly contagious and the actions of one farmer affect the risk
      of FMD occurring on other holdings; thus sizeable externalities are generated.
      Control therefore requires coordination within and between countries. These
      externalities imply that FMD control produces a significant amount of public
      goods, justifying the need for national and international public investment.
      Equipping poor countries with the tools needed to control FMD will involve the
      long term development of state veterinary services that in turn will deliver
      wider benefits to a nation including the control of other livestock diseases. 

PMID- 23958458
TI  - Iloprost in pulmonary hypertension due to sub-massive pulmonary embolism: report
      of two cases.

PMID- 23958459
TI  - Functional and dynamic response characteristics of a custom composite ankle foot
      orthosis for Charcot-Marie-Tooth patients.
AB  - BACKGROUND: Custom carbon-fiber composite ankle foot orthoses (AFOs) have been
      anecdotally reported to improve gait of Charcot-Marie-Tooth (CMT) patients. The
      purpose of the study was to characterize the spatio-temporal, joint kinetic and
      mechanical responses of a custom carbon fiber AFO during locomotion for persons
      diagnosed with CMT. METHODS: Eight volunteers were fitted with custom AFOs. Three
      of the devices were instrumented with eight strain gauges to measure surface
      deformation of the shell during dynamic function. Following a minimum 10 weeks
      accommodation period, plantar- and dorsiflexor strength was measured bilaterally.
      Volunteers then walked unbraced and braced, at their preferred pace over a force
      platform and instrumented walkway while being tracked with a 12-camera motion
      capture system. Strength, spatio-temporal and lower extremity joint kinetic
      parameters were evaluated between conditions (single subject) using the model
      statistic procedure. Mechanical loads were presented descriptively. RESULTS: All
      participants walked faster (89.4 +/- 13.3 vs 115.6 +/- 18.0 cm/s) in the braced
      condition with ankle strength negatively correlated to speed increase. As Delta
      velocity increased, maximum joint moments during loading response shifted from
      the hip joint to the ankle and knee joints. During propulsion, the hip joint
      moment dominated. Subjects exhibiting the greatest and least Delta velocity
      imposed an average load of 54.6% and 16.6% of body weight on the braces,
      respectively. Energy storage in the brace averaged 9.6 +/- 6.6J/kg. CONCLUSION:
      Subject-specific effects of a custom AFO on gait for CMT patients were
      documented. The force-deflection properties of carbon-fiber composite braces may
      be important considerations in their design.

PMID- 23958460
TI  - Correction: Hyperprolactinemia with antipsychotic drugs in children and
      adolescents.

PMID- 23958461
TI  - Renal cancer-selective Englerin A induces multiple mechanisms of cell death and
      autophagy.
AB  - Renal cell carcinoma (RCC), the most common malignancy of the kidney, is
      refractory to standard therapy and has an incidence that continues to rise.
      Screening of plant extracts in search of new agents to treat RCC resulted in the
      discovery of englerin A (EA), a natural product exhibiting potent selective
      cytotoxicity against renal cancer cells. Despite the establishment of synthetic
      routes to the synthesis of EA, very little is known about its mechanism of
      action. The results of the current study demonstrate for the first time that EA
      induces apoptosis in A498 renal cancer cells in addition to necrosis. The
      induction of apoptosis by EA required at least 24 h and was caspase independent.
      In addition, EA induced increased levels of autophagic vesicles in A498 cells
      which could be inhibited by nonessential amino acids (NEAA), known inhibitors of
      autophagy. Interestingly, inhibition of autophagy by NEAA did not diminish cell
      death suggesting that autophagy is not a cell death mechanism and likely
      represents a cell survival mechanism which ultimately fails. Apart from cell
      death, our results demonstrated that cells treated with EA accumulated in the G2
      phase of the cell cycle indicating a block in G2/M transition. Moreover, our
      results determined that EA inhibited the activation of both AKT and ERK, kinases
      which are activated in cancer and implicated in unrestricted cell proliferation
      and induction of autophagy. The phosphorylation status of the cellular energy
      sensor, AMPK, appeared unaffected by EA. The high renal cancer selectivity of EA
      combined with its ability to induce multiple mechanisms of cell death while
      inhibiting pathways driving cell proliferation, suggest that EA is a highly
      unique agent with great potential as a therapeutic lead for the treatment of RCC.

PMID- 23958462
TI  - Sinonasal squamous cell carcinomas: clinical outcomes and predictive factors.
AB  - This was a retrospective study of 33 patients treated for sinonasal squamous cell
      carcinoma between 1995 and 2008. Epidemiological, clinical, histological, and
      therapeutic aspects of this series of patients were analysed, and their impacts
      on overall survival and disease-free survival established using the Kaplan-Meier
      method. A search for prognostic factors was made using a log-rank test. There
      were 27 men. The average age at diagnosis was 64.7 years. Tobacco-smoking was
      found to be a risk factor in 24 patients (72.7%). The median follow-up was 66
      months (range 0-99 months). Tumours were classified as T1 in 18.3%, T2 in 27.3%,
      T3 in 6%, and T4 in 48.5% of cases. Disease-free survival rates at 1 and 5 years
      were 58.5% and 46.1%, respectively, and overall survival rates were 70.3% and
      40%, respectively. Overall survival was correlated to tumour status (TNM,
      American Joint Committee on Cancer) (P = 0.010) and involvement of key structures
      (skull base, dura mater, brain, orbit, cavernous sinus, infratemporal fossa,
      skin) (P = 0.049). Surgery followed by radiotherapy improved overall survival (P
      = 0.005) and disease-free survival (P = 0.028) when compared to other treatment
      modalities. When compared to surgery alone, it improved disease-free survival (P
      = 0.049) regardless of tumour stage.

PMID- 23958463
TI  - N1-guanyl-1,7-diaminoheptane (GC7) enhances the therapeutic efficacy of
      doxorubicin by inhibiting activation of eukaryotic translation initiation factor
      5A2 (eIF5A2) and preventing the epithelial-mesenchymal transition in
      hepatocellular carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) cells undergo the epithelial-mesenchymal
      transition (EMT) during chemotherapy, which reduces the efficacy of doxorubicin
      based chemotherapy. We investigated N1-guanyl-1,7-diaminoheptane (GC7) which
      inhibits eukaryotic translation initiation factor 5A2 (eIF5A2) activation; eIF5A2
      is associated with chemoresistance. GC7 enhanced doxorubicin cytotoxicity in
      epithelial HCC cells (Huh7, Hep3B and HepG2) but had little effect in mesenchymal
      HCC cells (SNU387, SNU449). GC7 suppressed the doxorubicin-induced EMT in
      epithelial HCC cells; knockdown of eIF5A2 inhibited the doxorubicin-induced EMT
      and enhanced doxorubicin cytotoxicity. GC7 combination therapy may enhance the
      therapeutic efficacy of doxorubicin in HCC by inhibiting eIF5A2 activation and
      preventing the EMT.

PMID- 23958464
TI  - miR-128 and its target genes in tumorigenesis and metastasis.
AB  - MicroRNAs (miRNAs) are a class of endogenous, non-coding, 18-24 nucleotide length
      single-strand RNAs that could modulate gene expression at post-transcriptional
      level. Previous studies have shown that miR-128 enriched in the brain plays an
      important role in the development of nervous system and the maintenance of normal
      physical functions. Aberrant expression of miR-128 has been detected in many
      types of human tumors and its validated target genes are involved in cancer
      related biological processes such as cell proliferation, differentiation and
      apoptosis. In this review, we will summarize the roles of miR-128 and its target
      genes in tumorigenesis and metastasis. 

PMID- 23958465
TI  - Imagery and visual working memory: one and the same?
AB  - Although visual imagery and visual working memory are both defined by the ability
      to actively represent and manipulate visual information, it is not known whether
      they rely on common mechanisms. A recent study by Albers and colleagues directly
      investigates this issue, finding evidence of common internal representations in
      early visual areas. 

PMID- 23958466
TI  - Levels and actions of progesterone and its metabolites in the nervous system
      during physiological and pathological conditions.
AB  - Progesterone is synthesized and actively metabolized in the central and
      peripheral nervous system, into neuroactive steroid metabolites, such as
      dihydroprogesterone, allopregnanolone and isopregnanolone. Progesterone and/or
      its metabolites exert a variety of effects acting as physiological regulators of
      neuronal and glial development and plasticity, controlling reproduction,
      neuroendocrine events, mood and affection. In addition, these neuroactive
      steroids maintain neural homeostasis and exert neuroprotective actions. In
      agreement, metabolic pathways of progesterone are affected by modifications in
      the level of gonadal hormones and by pathology or injury with a regional
      specificity and in a sex-dimorphic way. Therefore, observations here summarized
      may provide a background to design sex-specific therapies based on progesterone
      metabolites. On this point of view, considering that one of the major limits of a
      therapy based on neuroactive steroids could be modifications in their plasma
      levels and their consequent peripheral effects, pharmacological treatments aimed
      to increase their levels in the nervous system could provide an interesting
      therapeutic option. 

PMID- 23958467
TI  - Neonatal allopregnanolone levels alteration: effects on behavior and role of the
      hippocampus.
AB  - Several works have pointed out the importance of the neurosteroid
      allopregnanolone for the maturation of the central nervous system and for adult
      behavior. The alteration of neonatal allopregnanolone levels in the first weeks
      of life alters emotional adult behavior and sensory gating processes. Without
      ruling out brain structures, some of these behavioral alterations seem to be
      related to a different functioning of the hippocampus in adult age. We focus here
      on the different behavioral studies that have revealed the importance of neonatal
      allopregnanolone levels for the adult response to novel environmental stimuli,
      anxiety-related behaviors and processing of sensory inputs (prepulse inhibition).
      An increase in neonatal physiological allopregnanolone levels decreases anxiety
      and increases novelty responses in adult age, thus affecting the individual
      response to environmental cues. These effects are also accompanied by a decrease
      in prepulse inhibition, indicating alterations in sensory gating that have been
      related to that present in disorders, such as schizophrenia. Moreover, behavioral
      studies have shown that some of these effects are related to a different
      functioning of the dorsal hippocampus, as the behavioral effects (decrease in
      anxiety and locomotion or increase in prepulse inhibition) of intrahippocampal
      allopregnanolone infusions in adult age are not present in those subjects in whom
      neonatal allopregnanolone levels were altered. Recent data indicated that this
      hippocampal involvement may be related to alterations in the expression of gamma
      aminobutyric-acid receptors containing alpha4 and delta subunits, molecular
      alterations that can persist into adult age and that can, in part, explain the
      reported behavioral disturbances. 

PMID- 23958468
TI  - From antibody to clinical phenotype, the black box of the antiphospholipid
      syndrome: pathogenic mechanisms of the antiphospholipid syndrome.
AB  - The antiphospholipid syndrome (APS) is diagnosed by the combination of vascular
      thrombosis and/or pregnancy morbidity and the detection of antiphospholipid
      antibodies (aPLs) in plasma. In the last few years, a great effort has been made
      to unravel the mechanism by which aPLs cause thrombosis and a vast amount of
      mechanisms have been proposed. aPLs were proposed to induce a prothrombotic state
      by influencing the cellular blood compartment, the plasma compartment, the
      vascular wall and even metabolic pathways beyond the hemostatic system. However,
      due to the diversity in the mechanisms and the differences in the methodology,
      the focus of the mechanistical studies in this field seems to be largely
      diffused. It is hard to imagine that aPLs can exert such a diversity of effects,
      resulting in either thrombosis and/or pregnancy morbidity and the relationship
      between aPLs and the clinical manifestations remains to be a mysterious "black
      box". In an attempt to get insight in what takes place inside the black box, we
      have analyzed 126 mechanistical studies on aPLs and discussed differences in the
      type of antibodies that were used, the involvement of beta2-glycoprotein I
      (beta2GPI), and the criteria used to diagnose APS patients. 

PMID- 23958470
TI  - 2-arachidonoylglycerol interferes with lithium-induced vomiting in the house musk
      shrew, Suncus murinus.
AB  - The role of the endocannabinoid system in vomiting has been previously studied
      using several animal species. These investigations have clearly demonstrated an
      anti-emetic role for the eCB, anandamide, in these animal models; however,
      research concerning the role of 2-arhachidonoylglycerol (2AG) has been less
      clear. The aim of the present study was to assess the effects of exogenous 2AG
      administration in the house musk shrew, Suncus murinus. In Experiment 1, shrews
      were injected with vehicle or 2AG (1, 2, 5, 10 mg/kg) 15 min prior to behavioral
      testing in which the frequency of vomiting episodes was observed. In Experiment
      2, shrews were pre-treated with 2AG (2, 5 mg/kg) prior to being administered the
      emetic drug, lithium chloride (LiCl). It was found that 2AG alone did not induce
      emesis, but interfered with vomiting in response to LiCl administration. The anti
      emetic effects of 2AG in Suncus murinus do not appear to be mediated by CB1
      receptors, as concomitant pretreatment with the CB1 receptor antagonist,
      SR141716, did not reverse the suppressive effects of 2AG. These results confirm
      that manipulations that increase levels of 2AG exert anti-emetic effects in the
      house musk shrew.

PMID- 23958469
TI  - Evidence-based care of older people with suspected cognitive impairment in
      general practice: protocol for the IRIS cluster randomised trial.
AB  - BACKGROUND: Dementia is a common and complex condition. Evidence-based guidelines
      for the management of people with dementia in general practice exist; however,
      detection, diagnosis and disclosure of dementia have been identified as potential
      evidence-practice gaps. Interventions to implement guidelines into practice have
      had varying success. The use of theory in designing implementation interventions
      has been limited, but is advocated because of its potential to yield more
      effective interventions and aid understanding of factors modifying the magnitude
      of intervention effects across trials. This protocol describes methods of a
      randomised trial that tests a theory-informed implementation intervention that,
      if effective, may provide benefits for patients with dementia and their carers.
      AIMS: This trial aims to estimate the effectiveness of a theory-informed
      intervention to increase GPs' (in Victoria, Australia) adherence to a clinical
      guideline for the detection, diagnosis, and management of dementia in general
      practice, compared with providing GPs with a printed copy of the guideline.
      Primary objectives include testing if the intervention is effective in increasing
      the percentage of patients with suspected cognitive impairment who receive care
      consistent with two key guideline recommendations: receipt of a i) formal
      cognitive assessment, and ii) depression assessment using a validated scale
      (primary outcomes for the trial). METHODS: The design is a parallel cluster
      randomised trial, with clusters being general practices. We aim to recruit 60
      practices per group. Practices will be randomised to the intervention and control
      groups using restricted randomisation. Patients meeting the inclusion criteria,
      and GPs' detection and diagnosis behaviours directed toward these patients, will
      be identified and measured via an electronic search of the medical records nine
      months after the start of the intervention. Practitioners in the control group
      will receive a printed copy of the guideline. In addition to receipt of the
      printed guideline, practitioners in the intervention group will be invited to
      participate in an interactive, opinion leader-led, educational face-to-face
      workshop. The theory-informed intervention aims to address identified barriers to
      and enablers of implementation of recommendations. Researchers responsible for
      identifying the cohort of patients with suspected cognitive impairment, and their
      detection and diagnosis outcomes, will be blind to group allocation. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry:
      ACTRN12611001032943 (date registered 28 September, 2011).

PMID- 23958471
TI  - Changes in volatile compounds of mouse urine as it ages: their interactions with
      water and urinary proteins.
AB  - Mice release a variety of chemical signals, particularly through urine, which
      mediate social interactions and endocrine function. Studies have been conducted
      to investigate the stability of urinary chemosignals in mice. Neuroendocrine and
      behavioral responses of mice to urine samples of male and female conspecifics
      which have aged for different amounts of time have been examined, demonstrating
      that the quality and intensity of signaling molecules in urine change over time.
      In this study, we monitored changes in volatile organic compounds (VOCs) released
      from male and female mouse urine following aging the urine samples. Substantial
      amounts of some VOCs were lost during the aging process of urine, whereas other
      VOCs increased. Considerable portions of the VOCs which exhibited the increased
      release were shown to have previously been dissolved in water and subsequently
      released as the urine dried. We also demonstrated that some VOCs decreased
      slightly due to their binding with the major urinary proteins (MUPs) and
      identified MUP ligands whose headspace concentrations increased as the urine
      aged. Our results underscore the important role of MUPs and the hydration status
      in the release of VOCs in urine, which may largely account for the changes in the
      quality and intensity of urinary signals over time. 

PMID- 23958472
TI  - Cognitive-enhancing and antioxidant activities of inhaled coriander volatile oil
      in amyloid beta(1-42) rat model of Alzheimer's disease.
AB  - Coriandrum sativum L., commonly known as coriander and belonging to the Apiaceae
      family is cultivated throughout the world for its nutritional value. In
      traditional medicine, coriander is recommended for the relief of pain, anxiety,
      flatulence, loss of appetite and convulsions. In the present study, the effects
      of inhaled coriander volatile oil (1% and 3%, daily, for 21days) extracted from
      C. sativum var. microcarpum on spatial memory performance were assessed in an
      Abeta(1-42) rat model of Alzheimer's disease. The Abeta(1-42)-treated rats
      exhibited the following: decrease of spontaneous alternations percentage within Y
      maze task and increase of working memory errors, reference memory errors and time
      taken to consume all five baits within radial arm maze task. Exposure to
      coriander volatile oil significantly improved these parameters, suggesting
      positive effects on spatial memory formation. Assessments of oxidative stress
      markers in the hippocampal tissue of Abeta(1-42)-treated rats showed a
      significant increase of superoxide dismutase (SOD), lactate dehydrogenase (LDH)
      and a decrease of glutathione peroxidase (GPX) specific activities along with an
      elevation of malondialdehyde (MDA) level. Coriander volatile oil significantly
      decreased SOD and LDH specific activities, increased GPX specific activity and
      attenuated the increased MDA level. Also, DNA cleavage patterns were absent in
      the coriander rats, thus suggesting antiapoptotic activity of the volatile oil.
      Therefore, our results suggest that exposure to coriander volatile oil
      ameliorates Abeta(1-42)-induced spatial memory impairment by attenuation of the
      oxidative stress in the rat hippocampus. 

PMID- 23958473
TI  - Effect of dietary sphingomyelin on absorption and fractional synthetic rate of
      cholesterol and serum lipid profile in humans.
AB  - BACKGROUND: Diets enriched with sphingolipids may improve blood lipid profiles.
      Studies in animals have shown reductions in cholesterol absorption and
      alterations in blood lipids after treatment with sphingomyelin (SM). However,
      minimal information exists on effect of SM on cholesterol absorption and
      metabolism in humans. The objective was to assess the effect of SM consumption on
      serum lipid concentrations and cholesterol metabolism in healthy humans. METHODS:
      Ten healthy adult males and females completed a randomized crossover study.
      Subjects consumed controlled diets with or without 1 g/day SM for 14 days
      separated by at least 4 week washout period. Serum lipid profile and markers of
      cholesterol metabolism including cholesterol absorption and synthesis were
      analyzed. RESULTS: Serum triglycerides, total, LDL- and VLDL- cholesterol were
      not affected while HDL cholesterol concentrations were increased (p = 0.043) by
      SM diet consumption. No change in cholesterol absorption and cholesterol
      fractional synthesis rate was observed with supplementation of SM compared to
      control. Intraluminal cholesterol solubilization was also not affected by
      consumption of SM enriched diet. CONCLUSIONS: In humans, 1 g/day of dietary SM
      does not alter the blood lipid profile except for an increased HDL-cholesterol
      concentration and has no effect on cholesterol absorption, synthesis and
      intraluminal solubilization compared to control. TRIAL REGISTRATION:
      Clinicaltrials.gov # NCT00328211.

PMID- 23958474
TI  - Differential effects of methoxyamine on doxorubicin cytotoxicity and genotoxicity
      in MDA-MB-231 human breast cancer cells.
AB  - Pharmacological inhibition of DNA repair is a promising approach to increase the
      effectiveness of anticancer drugs. The chemotherapeutic drug doxorubicin (Dox)
      may act, in part, by causing oxidative DNA damage. The base excision repair (BER)
      pathway effects the repair of many DNA lesions induced by reactive oxygen species
      (ROS). Methoxyamine (MX) is an indirect inhibitor of apurinic/apyrimidinic
      endonuclease 1 (APE1), a multifunctional BER protein. We have evaluated the
      effects of MX on the cytotoxicity and genotoxicity of Dox in MDA-MB-231
      metastatic breast cancer cells. MX has little effects on the viability and
      proliferation of Dox-treated cells. However, as assessed by the cytokinesis-block
      micronucleus assay (CBMN), MX caused a significant 1.4-fold increase (P<0.05) in
      the frequency of micronucleated binucleated cells induced by Dox, and also
      altered the distribution of the numbers of micronuclei. The fluorescence probe
      dihydroethidium (DHE) indicated little production of ROS by Dox. Overall, our
      results suggest differential outcomes for the inhibition of APE1 activity in
      breast cancer cells exposed to Dox, with a sensitizing effect observed for
      genotoxicity but not for cytotoxicity. 

PMID- 23958475
TI  - The effects of initial movement dynamics on human responses to postural
      perturbations.
AB  - Falls are a major cause of injury, and often occur while turning, reaching, or
      bending. Yet, we have little understanding of how an ongoing feet-in place
      activity at the onset of imbalance, and its associated cognitive and
      biomechanical demands, influence our ability to recover balance. In the current
      study, we used an ankle-rocking paradigm to determine how the nature of the
      baseline task influences the balance recovery response to a backward support
      surface translation. Fourteen participants were instructed to "recover balance
      without stepping" and were perturbed at vertical while standing quietly ("S"),
      while ankle rocking and moving forward ("A_f"), or while ankle rocking and moving
      backward ("A_b"). The results showed that changes in rocking velocity at the time
      of the perturbation elicited changes in the incidence of stepping, magnitude of
      trunk angular displacements (p<.01), and the onset latencies of distal muscles
      (gastrocnemius and soleus, both p<.01) used to recover balance. In addition,
      plots of onset latencies across all muscles showed that onset latencies appeared
      to occur earlier in many muscles when participants held a static position
      compared to when they performed a dynamic task at the onset of the perturbation.
      The results suggest that muscle activities used to recover balance are tailored
      to the nature of the perturbation and the ongoing task, and that onset latencies
      are later when participants are performing a dynamic as opposed to static task at
      the time of a perturbation. These findings support previous research suggesting
      that automatic postural responses are highly adaptable to environmental,
      situational, and task demands. 

PMID- 23958476
TI  - Increased forefoot loading is associated with an increased plantar flexion
      moment.
AB  - The aim of this study was to identify the cascade of effects leading from
      alterations in force generation around the ankle joint to increased plantar
      pressures under the forefoot. Gait analysis including plantar pressure
      measurement was performed at an individually preferred and a standardized,
      imposed gait velocity in diabetic subjects with polyneuropathy (n=94), without
      polyneuropathy (n=39) and healthy elderly (n=19). The plantar flexion moment at
      40% of the stance phase was negatively correlated with the displacement rate of
      center of pressure (r=-.749, p<.001 at the imposed, and r=-.693, p<.001 at the
      preferred gait velocity). Displacement rate of center of pressure was strongly
      correlated with forefoot loading (r=-.837, p<.001 at the imposed, and r=-.731,
      p<.001 at the preferred gait velocity). People with a relatively high plantar
      flexion moment at 40% of the stance phase, have a faster forward transfer of
      center of pressure and consequently higher loading of the forefoot. This
      indicates that interventions aimed at increasing the control of the roll-off of
      the foot may contribute to a better plantar pressure distribution. 

PMID- 23958478
TI  - Clinical pharmacology of n-3 polyunsaturated fatty acids: non-lipidic metabolic
      and hemodynamic effects in human patients.
AB  - A high dietary intake of n-3 long chain polyunsaturated fatty acids (PUFA),
      eicosapentaenoic and docosahexaenoic acids, is associated with a reduced
      incidence of coronary events. Supplementation with pharmacological doses of the
      same may improve survival in patients with previous myocardial infarction and
      established heart failure. Such protective effects may be explained by the action
      of n-3 PUFA on systemic inflammation, hypertension, endothelial dysfunction,
      thrombosis, cardiac arrhythmias, heart rate variability and atherosclerotic
      plaque instability, which are involved in the pathogenesis of these clinical
      conditions. In this short paper we will review the evidence in support of these
      pleiotropic effects of n-3 fatty acids. 

PMID- 23958479
TI  - Omega-3 polyunsaturated fatty acids in the treatment of atherogenic dyslipidemia.
AB  - Epidemiological studies have established an association between high
      triglycerides (TG) plasma levels and increased cardiovascular risk. Increased TG
      levels, commonly coupled with low HDL-C levels, are common in high cardiovascular
      risk subjects including those with dyslipidemia, metabolic syndrome and type 2
      diabetes. Management of hypertriglyceridemia (HTG) includes lifestyle
      modification for mild-to-moderate HTG and pharmacological therapies for the
      treatment of high and very high TG levels. Among drugs, fibrates, nicotinic acid
      and omega-3 polyunsaturated fatty acids may be considered. Omega-3 fatty acids
      reduce plasma TG levels by several mechanisms; beside the effects on TG, omega-3
      can also influence the levels of other lipids and lipoproteins including HDL-C
      and LDL-C. Clinical trials have also shown that omega-3 fatty acid
      supplementation is effective also when added in combination with other lipid
      lowering drugs. These findings suggest that omega-3 fatty acids may be usefully
      considered for the management of high TG levels. 

PMID- 23958480
TI  - Long-term effect of high dose omega-3 fatty acid supplementation for secondary
      prevention of cardiovascular outcomes: A meta-analysis of randomized, placebo
      controlled trials [corrected].
AB  - BACKGROUND: Although omega-3 fatty acids have well documented properties which
      would reduce the cardiovascular (CV) disease risk, the evidence from randomized
      controlled trials (RCTs) remains inconclusive. We performed a meta-analysis of
      the available RCTs for investigating the CV preventive effect of administrating
      at least 1 gram/day, and for at least 1 year, omega-3 fatty acid supplements to
      patients with existing CV disease. METHODS: RCTs published up to March 2013 were
      searched from PubMed, EMBASE, and the Cochrane Library. Two of us independently
      reviewed and selected eligible trials. RESULTS: Of 360 articles retrieved, 11
      randomized, double-blind, placebo controlled trials fulfilling inclusion
      criteria, overall involving 15,348 patients with a history of CV disease, were
      considered in the final analyses. No statistically significant association was
      observed for all-cause mortality (RR, 0.89; 95% CI, 0.78 to 1.02) and stroke (RR,
      1.31; 95% CI, 0.90 to 1.90). Conversely, statistically significant protective
      effects were observed for cardiac death (RR, 0.68; 95% CI, 0.56 to 0.83), sudden
      death (RR, 0.67; 95% CI, 0.52 to 0.87), and myocardial infarction (RR, 0.75; 95%
      CI, 0.63 to 0.88). CONCLUSION: Overall, our results supply evidence that long
      term effect of high dose omega-3 fatty acid supplementation may be beneficial for
      the onset of cardiac death, sudden death and myocardial infarction among patients
      with a history of cardiovascular disease.

PMID- 23958481
TI  - Outcomes for a case series of unruptured anterior communicating artery aneurysm
      surgery.
AB  - Surgical outcomes following repair of unruptured anterior communicating artery
      (AcomA) aneurysms have not been adequately addressed in the literature. We
      present our operative experiences in a consecutive series of 103 patients with
      115 unruptured AcomA aneurysms. Clinical results, operative complications,
      angiographic outcomes and prognostic factors associated with surgery are
      presented. Of the 115 aneurysm repairs attempted, 114 were treated by clipping or
      excision and suture. One aneurysm, less than 2mm, was wrapped. Six patients
      (5.8%; 95% confidence interval [CI], 2.5-12.4) experienced a new permanent
      neurological deficit. There was no postoperative mortality. Transient morbidity
      occurred in 11 patients (10.7%; 95% CI, 5.9-18.3), including transient anosmia
      (four patients), acute postoperative confusion and memory disturbances (four
      patients), extradural haematoma requiring surgery (two patients) and
      cerebrospinal fluid rhinorrhea (one patient). Of the 84 aneurysms (73.0%) that
      had documented postoperative angiography, 82 (97.6%) had complete obliteration of
      the aneurysm and two (2.4%) had neck remnants (mean angiographic follow-up 28.0
      months; range, 1.6-146.4 months). Retreatment was performed in one patient
      (1.0%). Logistic regression analysis of risk factors revealed that aneurysm size
      (p<0.01) was a significant predictor of outcome. There was no incidence of
      subarachnoid haemorrhage in the 272 person years of follow-up. In the current
      study, surgical treatment of unruptured AcomA aneurysms resulted in 5.8%
      morbidity and no mortality. The robustness of aneurysm repair achieved by open
      microsurgery is an important consideration when considering the option between
      endovascular and microsurgical treatment for unruptured AcomA aneurysms.

PMID- 23958482
TI  - Acute pseudotumoral hemicerebellitis: diagnosis and neurosurgical considerations
      of a rare entity.
AB  - Acute pseudotumoral hemicerebellitis is an exceptionally rare unilateral
      presentation of acute cerebellitis mimicking a tumor. It typically has a benign
      course without specific therapy; thus, recognizing this entity is important to
      avoid needless surgical intervention. MRI provides the key for diagnosis and
      usually reveals a diffusely swollen cerebellar hemisphere with no well-defined
      mass. Some patients will require neurosurgical assistance by means of
      ventriculostomy or posterior fossa decompression. We present a 17-year-old girl
      with pseudotumoral hemicerebellitis, review the available literature, and discuss
      the diagnosis and therapeutic dilemma from the neurosurgical perspective. 

PMID- 23958483
TI  - Preoperative long-acting octreotide treatment for invasive thyrotropin-secreting
      pituitary macroadenoma after previous radioiodine thyroid ablation.
AB  - We report a 33-year-old woman with invasive thyrotropin-secreting pituitary
      adenoma after previous thyroid ablation with radioiodine who was successfully
      treated with transsphenoidal surgery after pre-treatment with octreotide-LAR for
      10 months. Since invasive and aggressive thyrotropin-secreting macroadenomas are
      more frequently observed in patients who have undergone thyroid ablation, we
      suggest preoperative treatment with somatostatin analogs should be considered in
      these patients to reduce serum thyrotropin and stabilize or reduce tumor size.

PMID- 23958484
TI  - [Where is the Anatolian Journal of Cardiology heading? What it has been
      experiencing?].

PMID- 23958486
TI  - Cannabis users have higher premorbid IQ than other patients with first onset
      psychosis.
AB  - BACKGROUND: A number of studies have reported that patients with psychosis who
      use cannabis have better cognitive performance than those who do not. This is
      surprising as cannabis can impair cognition in healthy subjects. An obvious
      question is whether the better current performance of psychotic patients who have
      used cannabis is a reflection of their having a higher premorbid IQ than those
      psychotic patients who haven't used cannabis. AIM: In a sample of patients at
      their first episode of psychosis, we tested the hypothesis that patients who
      smoked cannabis would have a higher premorbid IQ than patients who did not.
      METHODOLOGY: 279 participants (119 patients and 160 healthy controls) were
      assessed in order to obtain current and premorbid IQ measures and detailed
      information on cannabis use. We examined the association between cannabis use and
      both premorbid and current IQ in patients and controls. RESULTS: Patients who had
      ever smoked cannabis had significantly higher current (p<.001) and premorbid IQ
      (p=.004) compared to patients who had never used cannabis. This difference was
      not found among controls. CONCLUSIONS: These findings suggest that the better
      cognitive performance of patients with their first episode of psychosis who have
      used cannabis compared with those who haven't is due to the better premorbid IQ
      of the former.

PMID- 23958488
TI  - The effect of multiple allergen immunotherapy on exhaled nitric oxide in adults
      with allergic rhinitis.
AB  - BACKGROUND: There is a lack of objective measures of the clinical efficacy of
      allergen immunotherapy which relies on patients' perception about the effect of
      this treatment. We studied whether the fraction of exhaled nitric oxide is
      affected by multiple allergen immunotherapy in polysensitized adult subjects with
      allergic rhinitis. We also looked for associations between exhaled nitric oxide
      and subjects' demographics, symptom scores, and pulmonary function tests.
      METHODS: Twenty adult, polysensitized subjects with seasonal and perennial
      allergic rhinitis who chose to undergo allergen immunotherapy were enrolled. They
      were evaluated at baseline, and 4, 8, 12, 24, and 52 weeks later. Exhaled nitric
      oxide was reported as the mean of triplicate determinations. FINDINGS: Our
      results indicate that multiple allergen immunotherapy did not affect exhaled
      nitric oxide levels and such levels did not correlate with subjects' demographics
      and pulmonary function tests. However, exhaled nitric oxide was associated with
      rhinoconjuctivitis and asthma symptom scores at the end of the study.
      CONCLUSIONS: In polysensitized adult subjects with allergic rhinitis, exhaled
      nitric oxide levels are unaffected by multiple allergen immunotherapy.

PMID- 23958487
TI  - Cognitive profiles of three clusters of patients with a first-episode psychosis.
AB  - OBJECTIVE: The primary objective was to identify specific groups of patients with
      a first-episode psychosis based on family history, obstetric complications,
      neurological soft signs, and premorbid functioning. The secondary objective was
      to relate these groups with cognitive variables. METHOD: A total of 62 first
      episode psychoses were recruited from adult and child and adolescent mental
      health services. The inclusion criteria were patients between 7 and 65 years old
      (real range of the samples was 13-35 years old), two or more psychotic symptoms
      and less than one year from the onset of the symptoms. Premorbid functioning
      (PAS), soft signs (NES), obstetric complications and a neuropsychological battery
      (CPT, TMTA/TMTB, TAVEC/TAVECI, Stroop, specific subtest of WAIS-III/WISC-IV) were
      administered. RESULTS: We found three clusters: 1) higher neurodevelopment
      contribution (N=14), 2) higher genetic contribution (N=30), and 3) lower
      neurodevelopment contribution (N=18). Statistical differences were found between
      groups in TMTB, learning curve of the TAVEC, digits of the WAIS and premorbid
      estimated IQ, the cluster 1 being the most impaired. CONCLUSIONS: A cluster
      approach could differentiate several groups of patients with different cognitive
      performance. Neuropsychological interventions, as cognitive remediation, should
      be addressed specifically to patients with more impaired results.

PMID- 23958489
TI  - Passivity-based sliding mode control for a polytopic stochastic differential
      inclusion system.
AB  - Passivity-based sliding mode control for a polytopic stochastic differential
      inclusion (PSDI) system is considered. A control law is designed such that the
      reachability of sliding motion is guaranteed. Moreover, sufficient conditions for
      mean square asymptotic stability and passivity of sliding mode dynamics are
      obtained by linear matrix inequalities (LMIs). Finally, two examples are given to
      illustrate the effectiveness of the proposed method. 

PMID- 23958490
TI  - Finite-time Hinfinity control for a class of Markovian jump systems with mode
      dependent time-varying delays via new Lyapunov functionals.
AB  - This paper is concerned with the problem of finite-time Hinfinity control for a
      class of Markovian jump systems with mode-dependent time-varying delays via new
      Lyapunov functionals. In order to reduce conservatism, a new Lyapunov-Krasovskii
      functional is constructed. Based on the derived condition, the reliable Hinfinity
      control problem is solved, and the system trajectory stays within a prescribed
      bound during a specified time interval. Finally, numerical examples are given to
      demonstrate the proposed approach is more effective than some existing ones. 

PMID- 23958491
TI  - Cat Swarm Optimization algorithm for optimal linear phase FIR filter design.
AB  - In this paper a new meta-heuristic search method, called Cat Swarm Optimization
      (CSO) algorithm is applied to determine the best optimal impulse response
      coefficients of FIR low pass, high pass, band pass and band stop filters, trying
      to meet the respective ideal frequency response characteristics. CSO is generated
      by observing the behaviour of cats and composed of two sub-models. In CSO, one
      can decide how many cats are used in the iteration. Every cat has its' own
      position composed of M dimensions, velocities for each dimension, a fitness value
      which represents the accommodation of the cat to the fitness function, and a flag
      to identify whether the cat is in seeking mode or tracing mode. The final
      solution would be the best position of one of the cats. CSO keeps the best
      solution until it reaches the end of the iteration. The results of the proposed
      CSO based approach have been compared to those of other well-known optimization
      methods such as Real Coded Genetic Algorithm (RGA), standard Particle Swarm
      Optimization (PSO) and Differential Evolution (DE). The CSO based results confirm
      the superiority of the proposed CSO for solving FIR filter design problems. The
      performances of the CSO based designed FIR filters have proven to be superior as
      compared to those obtained by RGA, conventional PSO and DE. The simulation
      results also demonstrate that the CSO is the best optimizer among other relevant
      techniques, not only in the convergence speed but also in the optimal
      performances of the designed filters. 

PMID- 23958492
TI  - Effects of normobaric oxygen on the progression of focal cerebral ischemia in
      rats.
AB  - Normobaric oxygen (NBO) reduces infarction at 24-48 h in experimental models of
      focal cerebral ischemia. However, to be clinically relevant, longer term safety
      and efficacy must be explored. Here, we assessed the effects of NBO on glial
      activation, neurovascular recovery, and behavioral outcomes at 2 weeks after
      transient focal ischemia in rats. 100 min transient focal ischemia was induced by
      intraluminal occlusion of the middle cerebral artery in adult male Sprague-Dawley
      rats. Animals were randomized into sham, controls or 85'NBO started 15 min after
      ischemic onset. Infarct volumes and behavioral outcomes were blindly quantified.
      Immunohistochemistry was used to examine the effects of NBO on glial activation
      and neurovascular responses. After 2 weeks of reperfusion the infarct volume was
      marked reduced in animals subjected to NBO. They also had better outcomes in
      forelimb placement test and in body-swing test and weight loss reduction. After
      14 days, NBO decreased expression of Iba1, a marker of activated microglia, and
      GFAP, a marker of activated astrocytes. NBO treatment had no detectable effect on
      angiogenesis. These results suggest that protective effects of NBO may persist
      for up to 2 weeks post-stroke.

PMID- 23958493
TI  - Estimation of placental and lactational transfer and tissue distribution of
      atrazine and its main metabolites in rodent dams, fetuses, and neonates with
      physiologically based pharmacokinetic modeling.
AB  - Atrazine (ATR) is a widely used chlorotriazine herbicide, a ubiquitous
      environmental contaminant, and a potential developmental toxicant. To
      quantitatively evaluate placental/lactational transfer and fetal/neonatal tissue
      dosimetry of ATR and its major metabolites, physiologically based pharmacokinetic
      models were developed for rat dams, fetuses and neonates. These models were
      calibrated using pharmacokinetic data from rat dams repeatedly exposed (oral
      gavage; 5mg/kg) to ATR followed by model evaluation against other available rat
      data. Model simulations corresponded well to the majority of available
      experimental data and suggest that: (1) the fetus is exposed to both ATR and its
      major metabolite didealkylatrazine (DACT) at levels similar to maternal plasma
      levels, (2) the neonate is exposed mostly to DACT at levels two-thirds lower than
      maternal plasma or fetal levels, while lactational exposure to ATR is minimal,
      and (3) gestational carryover of DACT greatly affects its neonatal dosimetry up
      until mid-lactation. To test the model's cross-species extrapolation capability,
      a pharmacokinetic study was conducted with pregnant C57BL/6 mice exposed (oral
      gavage; 5mg/kg) to ATR from gestational day 12 to 18. By using mouse-specific
      parameters, the model predictions fitted well with the measured data, including
      placental ATR/DACT levels. However, fetal concentrations of DACT were
      overestimated by the model (10-fold). This overestimation suggests that only
      around 10% of the DACT that reaches the fetus is tissue-bound. These rodent
      models could be used in fetal/neonatal tissue dosimetry predictions to help
      design/interpret early life toxicity/pharmacokinetic studies with ATR and as a
      foundation for scaling to humans. 

PMID- 23958494
TI  - Azathioprine desensitizes liver cancer cells to insulin-like growth factor 1 and
      causes apoptosis when it is combined with bafilomycin A1.
AB  - Hepatoblastoma is a primary liver cancer that affects children, due to the
      sensitivity of this tumor to insulin-like growth factor 1 (IGF-1). In this paper
      we show that azathioprine (AZA) is capable of inhibiting IGF1-mediated signaling
      cascade in HepG2 cells. The efficiency of AZA on inhibition of proliferation
      differs in the evaluated cell lines as follows: HepG2 (an experimental model of
      hepatoblastoma)>Hep3B (derived from a hepatocellular carcinoma)>HuH6 (derived
      from a hepatoblastoma)>>HuH7 (derived from a hepatocellular carcinoma)=Chang
      Liver cells (a non-malignant cellular model). The effect of AZA in HepG2 cells
      has been proven to derive from activation of Ras/ERK/TSC2, leading to activation
      of mTOR/p70S6K in a sustained manner. p70S6K phosphorylates IRS-1 in serine 307
      which leads to the uncoupling between IRS-1 and p85 (the regulatory subunit of
      PI3K) and therefore causing the lack of response of HepG2 to IGF-1. As a
      consequence, proliferation induced by IGF-1 is inhibited by AZA and autophagy
      increases leading to senescence of HepG2 cells. Our results suggest that AZA
      induces the autophagic process in HepG2 activating senescence, and driving to
      deceleration of cell cycle but not to apoptosis. However, when simultaneous to
      AZA treatment the autophagy was inhibited by bafilomycin A1 and the degradation
      of regulatory proteins of cell cycle (e.g. Rb, E2F, and cyclin D1) provoked
      apoptosis. In conclusion, AZA induces resistance in hepatoblastoma cells to IGF
      1, which leads to autophagy activation, and causes apoptosis when it is combined
      with bafilomycin A1. We are presenting here a novel mechanism of action of
      azathioprine, which could be useful in treatment of IGF-1 dependent tumors,
      especially in its combination with other drugs.

PMID- 23958495
TI  - TRPM7 channel regulates PDGF-BB-induced proliferation of hepatic stellate cells
      via PI3K and ERK pathways.
AB  - TRPM7, a non-selective cation channel of the TRP channel superfamily, is
      implicated in diverse physiological and pathological processes including cell
      proliferation. Recently, TRPM7 has been reported in hepatic stellate cells
      (HSCs). Here, we investigated the contribution role of TRPM7 in activated HSC-T6
      cell (a rat hepatic stellate cell line) proliferation. TRPM7 mRNA and protein
      were measured by RT-PCR and Western blot in rat model of liver fibrosis in vivo
      and PDGF-BB-activated HSC-T6 cells in vitro. Both mRNA and protein of TRPM7 were
      dramatically increased in CCl4-treated rat livers. Stimulation of HSC-T6 cells
      with PDGF-BB resulted in a time-dependent increase of TRPM7 mRNA and protein.
      However, PDGF-BB-induced HSC-T6 cell proliferation was inhibited by non-specific
      TRPM7 blocker 2-aminoethoxydiphenyl borate (2-APB) or synthetic siRNA targeting
      TRPM7, and this was accompanied by downregulation of cell cycle proteins, cyclin
      D1, PCNA and CDK4. Blockade of TRPM7 channels also attenuated PDGF-BB induced
      expression of myofibroblast markers as measured by the induction of alpha-SMA and
      Col1alpha1. Furthermore, the phosphorylation of ERK and AKT, associated with cell
      proliferation, decreased in TRPM7 deficient HSC-T6 cells. These observations
      suggested that TRPM7 channels contribute to perpetuated fibroblast activation and
      proliferation of PDGF-BB induced HSC-T6 cells via the activation of ERK and PI3K
      pathways. Therefore, TRPM7 may constitute a useful target for the treatment of
      liver fibrosis. 

PMID- 23958496
TI  - Calcineurin inhibitors recruit protein kinases JAK2 and JNK, TLR signaling and
      the UPR to activate NF-kappaB-mediated inflammatory responses in kidney tubular
      cells.
AB  - The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus are key drugs
      in current immunosuppressive regimes for solid organ transplantation. However,
      they are nephrotoxic and promote death and profibrotic responses in tubular
      cells. Moreover, renal inflammation is observed in CNI nephrotoxicity but the
      mechanisms are poorly understood. We have now studied molecular pathways leading
      to inflammation elicited by the CNIs in cultured and kidney tubular cells. Both
      CsA and tacrolimus elicited a proinflammatory response in tubular cells as
      evidenced by a transcriptomics approach. Transcriptomics also suggested several
      potential pathways leading to expression of proinflammatory genes. Validation and
      functional studies disclosed that in tubular cells, CNIs activated protein
      kinases such as the JAK2/STAT3 and TAK1/JNK/AP-1 pathways, TLR4/Myd88/IRAK
      signaling and the Unfolded Protein Response (UPR) to promote NF-kappaB activation
      and proinflammatory gene expression. CNIs also activated an Nrf2/HO-1-dependent
      compensatory response and the Nrf2 activator sulforaphane inhibited JAK2 and JNK
      activation and inflammation. A murine model of CsA nephrotoxicity corroborated
      activation of the proinflammatory pathways identified in cell cultures. Human
      CNIs nephrotoxicity was also associated with NF-kappaB, STAT3 and IRE1alpha
      activation. In conclusion, CNIs recruit several intracellular pathways leading to
      previously non-described proinflammatory actions in renal tubular cells.
      Identification of these pathways provides novel clues for therapeutic
      intervention to limit CNIs nephrotoxicity. 

PMID- 23958497
TI  - Fractalkine receptor is expressed in mature ovarian teratomas and required for
      epidermal lineage differentiation.
AB  - BACKGROUND: The goal of this study was to determine a predominant cell type
      expressing fractalkine receptor (CX3CR1) in mature ovarian teratomas and to
      establish functional significance of its expression in cell differentiation.
      METHODS: Specimens of ovarian teratoma and human fetal tissues were analyzed by
      immunohistochemistry for CX3CR1expression. Ovarian teratocarcinoma cell line PA-1
      was used as a model for cell differentiation. RESULTS: We found that the majority
      of the specimens contained CX3CR1-positive cells of epidermal lineage. Skin
      keratinocytes in fetal tissues were also CX3CR1- positive. PA-1 cells with
      downregulated CX3CR1 failed to express a skin keratinocyte marker cytokeratin 14
      when cultured on Matrigel in the presence of a morphogen, bone morphogenic
      protein 4 (BMP-4), as compared to those expressing scrambled shRNA. CONCLUSIONS:
      Here we demonstrate that CX3CR1 is expressed in both normally (fetal skin) and
      abnormally (ovarian teratoma) differentiated keratinocytes and is required for
      cell differentiation into epidermal lineage.

PMID- 23958498
TI  - Atg24-assisted mitophagy in the foot cells is necessary for proper asexual
      differentiation in Magnaporthe oryzae.
AB  - Macroautophagy-mediated glycogen catabolism is required for asexual
      differentiation in the blast fungus, Magnaporthe oryzae. However, the function(s)
      of selective subtypes of autophagy has not been studied therein. Here, we report
      that mitophagy, selective autophagic delivery of mitochondria to the vacuoles for
      degradation, occurs during early stages of Magnaporthe conidiation. Specifically,
      mitophagy was evident in the foot cells while being undetectable in aerial hyphae
      and/or conidiophores. We show that loss of MoAtg24, a sorting nexin related to
      yeast Snx4, disrupts mitophagy and consequently leads to highly reduced
      conidiation, suggesting that mitophagy in the foot cells plays an important role
      during asexual development in Magnaporthe. Ectopic expression of yeast ScATG32
      partially suppressed the conidiation initiation defects associated with MoATG24
      deletion. MoAtg24 was neither required for pexophagy nor for macroautophagy, or
      for MoAtg8 localization per se, but directly associated with and likely recruited
      mitochondria to the autophagic structures during mitophagy. Lastly, MoAtg24 was
      also required for oxidative stress response in Magnaporthe. 

PMID- 23958499
TI  - Accessory molecules for Toll-like receptors in Teleost fish. Identification of
      TLR4 interactor with leucine-rich repeats (TRIL).
AB  - The biosynthesis and activation of Toll-like receptors (TLRs) requires accessory
      proteins. In mammals, a number of accessory proteins have been characterized,
      that can be classified based on their function as ligand-recognition and delivery
      cofactors, chaperones and trafficking proteins. We identified the homologs in
      teleost fish genomes of mammalian accessory molecules and show their expression
      in transcriptome data sets. Further, we annotate in detail TLR4 interactor with
      leucine-rich repeats (tril) in zebrafish (Danio rerio) and in common carp
      (Cyprinus carpio). In mammals, TRIL is a functional component of the TLR4 complex
      and is important for TLR3 signaling, and is mainly expressed in the brain. In
      fish, the Tril molecule has many conserved features of mouse and human TRIL,
      containing 13 leucine-rich repeat domains, a fibronectin and a transmembrane
      domain. Zebrafish tril could not be detected in the latest assembly of the
      zebrafish genome (Zv9) and required manual annotation based on genome and
      transcriptome shotgun sequencing data sets. Carp tril was found in two copies in
      the draft genome. Both copies of carp tril are constitutively expressed in
      several organs, with the highest gene expression in muscle, skin and brain. In
      carp, the tril gene is expressed at high levels in endothelial cells and
      thrombocytes. We discuss the implication of the presence of most, but not all,
      accessory molecules for the biosynthesis and activation of tlr molecules in fish.

PMID- 23958500
TI  - Molecular basis for the catalytic inactivity of a naturally occurring near-null
      variant of human ALOX15.
AB  - Mammalian lipoxygenases belong to a family of lipid-peroxidizing enzymes, which
      have been implicated in cardiovascular, hyperproliferative and neurodegenerative
      diseases. Here we report that a naturally occurring mutation in the hALOX15 gene
      leads to expression of a catalytically near-null enzyme variant (hGly422Glu). The
      inactivity may be related to severe misfolding of the enzyme protein, which was
      concluded from CD-spectra as well as from thermal and chemical stability assays.
      In silico mutagenesis experiments suggest that most mutations at hGly422 have the
      potential to induce sterical clash, which might be considered a reason for
      protein misfolding. hGly422 is conserved among ALOX5, ALOX12 and ALOX15 isoforms
      and corresponding hALOX12 and hALOX5 mutants also exhibited a reduced catalytic
      activity. Interestingly, in the hALOX5 Gly429Glu mutants the reaction specificity
      of arachidonic acid oxygenation was shifted from 5S- to 8S- and 12R-H(p)ETE
      formation. Taken together, our data indicate that the conserved glycine is of
      functional importance for these enzyme variants and most mutants at this position
      lose catalytic activity. 

PMID- 23958501
TI  - Across-muscle coherence is modulated as a function of wrist posture during two
      digit grasping.
AB  - The purpose of this study was to investigate the extent to which correlated
      neural inputs, quantified as EMG-EMG coherence across intrinsic and extrinsic
      hand muscles, varied as a function of wrist angle during a constant force
      precision grip task. Eight adults (5 males; mean age 29 years) participated in
      the experiment. Subjects held an object using a two-digit precision grip at a
      constant force at a flexed, neutral, and extended wrist posture, while the EMG
      activity from intrinsic and extrinsic hand muscles was recorded through
      intramuscular fine-wire electrodes. The integral of z-transformed coherence
      computed across muscles pairs was greatest in the flexed wrist posture and
      significantly greater than EMG-EMG coherence measured in the neutral and extended
      wrist posture (P < 0.01 and 0.05, respectively). Furthermore, EMG-EMG coherence
      did not differ statistically between the extrinsic and intrinsic muscle pairs,
      even though it tended to be greater for the extrinsic muscle pair (P >= 0.063).
      These findings lend support to the notion of a functional role of correlated
      neural inputs to hand muscles for the task-dependent coordination of hand muscle
      activity that is likely mediated by somatosensory feedback.

PMID- 23958502
TI  - Differential effects of exercise intensities in hippocampal BDNF, inflammatory
      cytokines and cell proliferation in rats during the postnatal brain development.
AB  - It has been established that low intensities of exercise produce beneficial
      effects for the brain, while high intensities can cause some neuronal damage
      (e.g. exacerbated inflammatory response and cell death). Although these effects
      are documented in the mature brain, the influence of exercise intensities in the
      developing brain has been poorly explored. To investigate the impact of exercise
      intensity in developing rats, we evaluated the hippocampal level of brain derived
      neurotrophic factor (BDNF), inflammatory cytokines (TNFalpha, IL6 and IL10) and
      the occurrence of hippocampal cell degeneration and proliferation at different
      stages of postnatal brain development of rats submitted to two physical exercise
      intensities. To this point, male rats were divided into different age groups:
      P21, P31, P41 and P51. Each age group was submitted to two exercise intensities
      (low and high) on a treadmill over 10 consecutive days, except the control rats.
      We verified that the density of proliferating cells was significantly higher in
      the dentate gyrus of rats submitted to low-intensity exercise from P21 to P30
      compared with high-intensity exercise and control rats. A significant increase of
      proliferative cell density was found in rats submitted to high-intensity exercise
      from P31 to P40 when compared to low-intensity exercise and control rats.
      Elevated hippocampal levels of IL6 were detected in rats submitted to high
      intensity exercise from P21 to P30 compared to control rats. From P41 to P50
      period, higher levels of BDNF, TNFalpha and IL10 were found in the hippocampal
      formation of rats submitted to high-intensity exercise in relation to their
      control rats. Our data show that exercise-induced neuroplastic effects on BDNF
      levels and cellular proliferation in the hippocampal region are dependent on
      exercise intensity and developmental period. Thus, exercise intensity is an
      inflammation-inducing factor and exercise-induced inflammatory response during
      the postnatal brain development is also related to developmental stage. Our
      findings indicate that neuroplastic changes induced by exercise in developing
      rats depend on both age and training intensity. 

PMID- 23958503
TI  - Editorial comment.

PMID- 23958504
TI  - Severe obesity is associated with 3-fold higher radiation dose rate during
      ureteroscopy.
AB  - OBJECTIVE: To investigate and characterize the association between fluoroscopy
      radiation dose rate and various patient size metrics during ureteroscopy.
      MATERIALS AND METHODS: Fluoroscopy data were collected from 100 patients
      undergoing ureteroscopy for stone disease. Radiation dose rates were determined
      from fluoroscopy dose and time. Estimated entrance skin dose was calculated from
      air kerma (AK) by applying correction factors. Effective dose (ED) was estimated
      with Monte Carlo-based simulation software. Patient size metrics included body
      mass index (BMI), anterior-posterior (AP) midline distance, AP transrenal
      thickness, and region of interest (ROI) pixel value magnitude on computed
      tomography scout. Univariate and multivariate regression analyses were performed
      to determine the association between AK dose rate and patient size metrics,
      adjusting for laterality and stone location. RESULTS: Obese patients (>30
      kg/m(2)) comprised 46% of the cohort. Mean fluoroscopy time, displayed AK,
      entrance skin dose, and ED were 4.2 +/- 6.0 second, 1.2 +/- 2.1 mGy, 1.2 +/- 2.2
      mGy, and 0.08 +/- 0.15 mSv, respectively. Mean AK dose rate and ED dose rates
      were 0.30 +/- 0.23 mGy/second and 0.021 +/- 0.016 mSv/second, respectively.
      Compared with the nonobese category, the highest BMI category (>=35 kg/m(2)) had
      over a 3-fold higher mean AK rate (0.50 vs 0.16 mGy/second). On univariate and
      multivariate analysis, BMI, AP midline distance, AP transrenal thickness, and
      computed tomography scout region of interest pixel value magnitude were each
      significantly associated with dose rate. CONCLUSION: Larger patients experience
      higher radiation dose rates under fluoroscopy. Severely obese patients receive 3
      fold higher dose rates compared with nonobese patients. Given the higher
      incidence of stone disease in obese patients, all attempts should be made to
      minimize radiation exposure during ureteroscopy.

PMID- 23958505
TI  - Editorial comment.

PMID- 23958506
TI  - Copeptin as a novel biomarker in nocturnal enuresis.
AB  - OBJECTIVE: To investigate the relation between copeptin, arginine vasopressin
      (AVP), and nocturnal enuresis (NE). METHODS: Forty-four patients with NE and 44
      healthy children aged between 6 and 14 years were enrolled. Patients with
      nonmonosymptomatic and secondary NE were excluded from the study. A small
      questionnaire, filled by parents, collected information about sociodemographic
      characteristics. Blood was obtained for plasma AVP and copeptin concentrations.
      RESULTS: Copeptin levels were significantly lower in patient group (3.74 +/- 1.44
      pg/mL) than the control group (16.57 +/- 3.91 pg/mL), whereas AVP levels were not
      significantly different between groups. Copeptin levels were significantly lower
      in patients (3.17 +/- 1.15 pg/mL) who had bed-wetting 2 or more nights a week,
      which is considered as severe bed-wetting, than the patients (4.95 +/- 1.24
      pg/mL) who had bed-wetting 1 night or less than 1 night a week. CONCLUSION: This
      study demonstrates the presence of decreased levels of copeptin in patients with
      NE compared with healthy patients. AVP levels were not different between groups.
      To our knowledge, this is the first report assessing the relationship between
      copeptin and NE.

PMID- 23958507
TI  - Is percutaneous nephrolithotomy in solitary kidneys safe?
AB  - OBJECTIVE: To review our experience from a high volume stone center with a focus
      on efficacy, safety, and renal function. METHODS: Stones requiring percutaneous
      nephrolithotomy (PCNL) in patients with solitary kidneys can pose significant
      anxiety to the urologist. Limited data are available in published reports in this
      setting. A comprehensive retrospective review of medical records was performed on
      patients who underwent PCNL and had a solitary kidney or a single functioning
      renal unit. Data were collected on patient demographics, stone burden, outcomes,
      complications, and renal function. RESULTS: Of 378 PCNLs performed between
      January 2003 and September 2011, 22 were performed in 17 patients with a single
      functioning kidney. Three procedures were performed in a transplanted kidney. In
      those with solitary calculus, the longest mean length and stone surface area were
      37 mm and 825 mm(2), respectively. Stone-free rate was 59%. Auxiliary procedures
      were required in 6 cases, resulting in a stone-free rate of 77%. Median inpatient
      stay was 4 days. Serum creatinine values improved from 144 to 126 umol/L before
      and after the procedure and mean estimated glomerular filtration rate improved
      similarly from 51 to 59 mls/minute, respectively. Blood transfusion was required
      in 1 patient, sepsis developed in 3, and 2 patients required a stent for
      obstruction. CONCLUSION: PCNL in solitary kidneys is safe with an acceptable
      complication rate if performed in a high volume center. Outcomes are good,
      although auxiliary procedures may be necessary. Renal function remains stable or
      improves after procedure.

PMID- 23958508
TI  - North American consensus document on infection of penile prostheses.
AB  - OBJECTIVE: To issue a consensus document on the prevention, management, and
      research of infection associated with penile prostheses, as neither professional
      associations nor governmental entities have issued guidelines that are specific
      to this infection. METHODS: Sixteen North American experts on infection of penile
      prostheses were identified and assembled to select and discuss certain issues
      related to infection of penile prostheses. After performing an extensive search
      of clinically important issues in published reports, the 16 experts met twice in
      person to finalize the selection, discuss the issues that were deemed most
      important, and issue pertinent recommendations. RESULTS: Although many subjects
      relevant to infection of penile prostheses were initially identified, the experts
      selected 10 issues as currently being the most important issues and for which
      there exists some support in the published data. The examined issues involved
      prevention, management, or research of infections associated with penile
      prostheses. CONCLUSION: In the absence of pertinent guidelines, the consensus
      document issued by experts in the field of prosthetic urology is anticipated to
      improve the quality of patient care, streamline the prevention and management of
      infected penile prostheses, and stimulate collaborative research. Although this
      consensus document could serve as best practice recommendations, the lack of
      adherence to these recommendations would not indicate improper care.

PMID- 23958509
TI  - Editorial comment.

PMID- 23958510
TI  - The efficacy of extracorporeal magnetic stimulation for treatment of chronic
      prostatitis/chronic pelvic pain syndrome patients who do not respond to
      pharmacotherapy.
AB  - OBJECTIVE: To investigate the effect of extracorporeal magnetic stimulation (EMS)
      on symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men
      who did not respond to pharmacotherapy. METHODS: Patients with chronic pelvic
      pain and/or voiding symptoms in the absence of urinary tract infection for at
      least 3 months in spite of medication were included in this study. All patients
      underwent EMS for 6 weeks for a total of 12 sessions. The primary endpoint was
      the changes in total and pain scores of the National Institutes of Health Chronic
      Prostatitis Symptom Index (NIH-CPSI) at 24 weeks after treatment. Patients were
      also evaluated by International Prostate Symptom Score (IPSS), voiding diary,
      Benefit Satisfaction and Willingness (BSW) questionnaire, and patient perception
      of symptom improvement (PPSI). RESULTS: A total of 46 men were included, and data
      from 37 patients who completed this study were analyzed. The baseline vs 24 weeks
      mean NIH-CPSI score was total score 25.0 +/- 6.9 vs 15.6 +/- 7.7, pain score 11.8
      +/- 3.7 vs 6.9 +/- 4.7 (all P <.05). Total and subdomain sums of IPSS improved
      significantly after treatment, and the improvements were maintained until 24
      weeks. Patient voiding diaries demonstrated a tendency toward a decrease in all
      subdomains after treatment. In BSW, >70% of patients reported positive answers to
      each domain at 24 weeks after treatment. PPSI measured by the visual analog scale
      was maintained from immediately after treatment until 24 weeks. CONCLUSION: EMS
      offers a new treatment option for patients with CP/CPPS who do not respond to
      pharmacotherapy.

PMID- 23958511
TI  - Neurofibroma and epidermoid cyst: unexpected findings after first foreskin
      retraction.
AB  - We report here 2 unusual cases of tumor of the glans penis in children. Abnormal
      findings were found on a 12-year-old and a 13-year-old boy soon after their first
      foreskin retraction. Initial medical examination suggested inclusions of smegma
      and they were referred to our Department of Pediatric Urology. Complete resection
      was performed under general anesthesia. Histologic examination revealed an
      epidermoid cyst in the first patient and a solitary neurofibroma in the second.
      These patients represent respectively the third and the second cases of such
      entities described in the pediatric age group. Cautious examination is required
      for persistent inclusions of smegma.

PMID- 23958513
TI  - Complications of robotic surgery in pediatric urology: a single institution
      experience.
AB  - OBJECTIVE: To report our analysis of complications on pediatric robotic urologic
      procedures. METHODS: A retrospective review was performed for all robotic
      surgeries by pediatric urologists at a single pediatric institution, from the
      start of the robotic surgery program in February 2009 through February 2013. Data
      included patient demographics, intraoperative details, outcomes, and
      complications (Clavien system). RESULTS: The analysis included 136 patients.
      There were 10 different types of procedures performed by 3 pediatric urologists.
      There were no intraoperative complications, robotic malfunctions, conversions to
      open or laparoscopic surgery, or mortalities. There were 11 total complications
      (8.1%): 2 grade I (1.5%), 7 grade II (5.1%), and 2 grade IIIb (1.5%).
      Complications included ileus in 2 patients (1.5%), port site infection in 2
      (1.5%), urinary leak in 2 (1.5%), urinary retention in 2 (1.5%), urinary tract
      infection in 2 (1.5%), and stent migration in 1 (0.7%). The complication rate was
      in 3 of 10 infants (30%) and 8 of 126 noninfants (6.3%), P = .035. However, grade
      I, II, and IIIb complication rates were not significantly higher in infants vs
      noninfants, P = 1, .084, and .142, respectively. There was no difference in
      complication rates between the 3 surgeons. CONCLUSION: Pediatric robotic urologic
      procedures are safely performed with a relatively low complication rate and a low
      incidence of additional interventions owing to complications. Ongoing use of
      robotic technology in the pediatric population can be supported. Further reports
      are needed to validate our findings.

PMID- 23958515
TI  - Synthesis and biological evaluation of prodigiosene conjugates of porphyrin,
      estrone and 4-hydroxytamoxifen.
AB  - To generate the first series of prodigiosene conjugates, the tripyrrolic skeleton
      was appended to estrone, tamoxifen and porphyrin frameworks by way of ester
      linkers and various hydrocarbon chain lengths. The ability of the conjugates to
      inhibit various types of cancer cells was evaluated in vitro. The porphyrin
      conjugates did not exhibit significant activity. The estrone conjugates exhibited
      modest activity, for the most part. However, significantly greater growth
      inhibition activity against certain breast, colon, lung, leukemia, melanoma and
      prostate cell lines was noted. This unusual effect for this first generation
      model class of compound warrants further investigation and comparison to cases
      where estrogens are linked to prodigiosenes via connection points that do not
      feature in estrogen receptor binding. The 4-hydroxytamoxifen conjugates exhibit
      nanomolar range activity against the MCF-7 breast cancer cell line, paving the
      way to expand the scope and connectivity of prodigiosene-tamoxifen conjugates. 

PMID- 23958516
TI  - Design, synthesis, and structure-activity relationships of dihydrofuran-2-one and
      dihydropyrrol-2-one derivatives as novel benzoxazin-3-one-based mineralocorticoid
      receptor antagonists.
AB  - Dihydrofuran-2-one and dihydropyrrol-2-one derivatives were identified as novel,
      potent and selective mineralocorticoid receptor (MR) antagonists by the structure
      based drug design approach utilizing the crystal structure of MR/compound
      complex. Introduction of lipophilic substituents directed toward the unfilled
      spaces of the MR and identification of a new scaffold, dihydropyrrol-2-one ring,
      led to potent in vitro activity. Among the synthesized compounds, dihydropyrrol-2
      one 11i showed an excellent in vitro activity (MR binding IC50=43nM) and high
      selectivity over closely related steroid receptors such as the androgen receptor
      (AR), progesterone receptor (PR) and glucocorticoid receptor (GR) (>200-fold for
      AR and PR, 100-fold for GR). 

PMID- 23958517
TI  - Current understanding of molecular and cellular mechanisms in fibroplasia and
      angiogenesis during acute wound healing.
AB  - Cutaneous wound healing ultimately functions to facilitate barrier restoration
      following injury-induced loss of skin integrity. It is an evolutionarily
      conserved, multi-cellular, multi-molecular process involving co-ordinated inter
      play between complex signalling networks. Cellular proliferation is recognised as
      the third stage of this sequence. Within this phase, fibroplasia and angiogenesis
      are co-dependent processes which must be successfully completed in order to form
      an evolving extracellular matrix and granulation tissue. The resultant structures
      guide cellular infiltration, differentiation and secretory profile within the
      wound environment and consequently have major influence on the success or failure
      of wound healing. This review integrates in vitro, animal and human in vivo
      studies, to provide up to date descriptions of molecular and cellular
      interactions involved in fibroplasia and angiogenesis. Significant molecular
      networks include adhesion molecules, proteinases, cytokines and chemokines as
      well as a plethora of growth factors. These signals are produced by, and affect
      behaviour of, cells including fibroblasts, fibrocytes, keratinocytes, endothelial
      cells and inflammatory cells resulting in significant cellular phenotypic and
      functional plasticity, as well as controlling composition and remodelling of
      structural proteins including collagen and fibronectin. The interdependent
      relationship between angiogenesis and fibroplasia relies on dynamic reciprocity
      between cellular components, matrix proteins and bioactive molecules. Unbalanced
      regulation of any one component can have significant consequences resulting in
      delayed healing, chronic wounds or abnormal scar formation. Greater understanding
      of angiogenic and fibroplastic mechanisms underlying chronic wound pathogenesis
      has identified novel therapeutic targets and enabled development of improved
      treatment strategies including topical growth factors and skin substitutes. 

PMID- 23958518
TI  - Oxaliplatin-induced liver injury mimicking metastatic tumor on images: a case
      report.
AB  - Oxaliplatin-based chemotherapy is widely used for advanced colorectal cancer
      treatment, but it occasionally induces liver injury that is characterized
      histologically by sinusoidal dilatation, hepatic plate atrophy and/or venular
      obstruction. Most of the patients do not reveal apparent radiological
      abnormalities, however. Here, we report the case of a 47-year-old man with a
      radiologically detectable mass-forming oxaliplatin-induced sinusoidal injury that
      mimicked multiple liver tumors. These mass lesions were found on computed
      tomography images after the administration of six cycles of folinic acid,
      fluorouracil and oxaliplatin therapy as adjuvant chemotherapy for Stage III
      rectal cancer. The patient had to undergo liver resection because imaging studies
      could not exclude metastases. The histological examination revealed that a
      resected mass lesion was composed of severe sinusoidal dilatation. Milder
      dilatation was also seen in the surrounding parenchyma. We diagnosed the patient
      as having an oxaliplatin-induced sinusoidal injury with severe deviation. As
      oxaliplatin is a standard agent in colorectal cancer therapy today, all
      clinicians and pathologists should be aware of such non-neoplastic lesions as one
      of the rare differential diagnoses of metastatic liver tumor, to prevent
      overtreatment. 

PMID- 23958519
TI  - Authors' response: single versus combination antibiotic therapy in adults
      hospitalised with community acquired pneumonia.

PMID- 23958520
TI  - Case managed community aged care: what is the evidence for effects on service use
      and costs?
AB  - OBJECTIVE: To evaluate the effects of case management in community aged care
      (CMCAC) interventions on service use and costs. METHOD: Five databases were
      searched from inception to 2011 July to include randomized control trials and
      comparative observational English studies. Results were summarized by using the
      best-evidence synthesis approach. RESULTS: Twenty-one studies were included.
      Available studies supported improvements in clients' use of case management
      services (all of the four studies), some community services (8 of the 10) and
      nursing home admission and stay (around one half), delay of nursing home
      placement (all of the two studies), and achieving cost neutrality (8 of the 11).
      The effects on medical care utilization were varying. DISCUSSION: In general,
      these positive effects justify the further development and refinement of CMCAC
      programs. Result applicability is limited by only including English studies. Cost
      studies applying a societal perspective, and full economic appraisals where
      appropriate are warranted.

PMID- 23958521
TI  - Sensitization of peripheral sensory nerves by mediators from colonic biopsies of
      diarrhea-predominant irritable bowel syndrome patients: a role for PAR2.
AB  - OBJECTIVES: This study examined whether mediators from biopsies of human
      irritable bowel syndrome (IBS) colons alter intrinsic excitability of colonic
      nociceptive dorsal root ganglion (DRG) neurons by a protease activated receptor 2
      (PAR2)-mediated mechanism. METHODS: Colonic mucosal biopsies from IBS patients
      with constipation (IBS-C) or diarrhea (IBS-D) and from healthy controls were
      incubated in medium, and supernatants were collected. Small-diameter mouse
      colonic DRG neurons were incubated in supernatants overnight and perforated patch
      current-clamp recordings obtained. Measurements of rheobase and action potential
      discharge at twice rheobase were compared between IBS and controls to assess
      differences in intrinsic excitability. RESULTS: Supernatants from IBS-D patients
      elicited a marked increase in neuronal excitability compared with controls. These
      changes were consistent among individual patients but the relative contribution
      of rheobase and action potential discharge varied. In contrast, no differences in
      neuronal excitability were seen with IBS-C patient supernatants. The increased
      excitability seen with IBS-D supernatant was not observed in PAR2 knockout mice.
      A cysteine protease inhibitor, which had no effect on the pronociceptive actions
      of a serine protease, inhibited the proexcitatory actions of IBS-D supernatant.
      CONCLUSIONS: Soluble mediators from colonic biopsies from IBS-D but not IBS-C
      patients sensitized colonic nociceptive DRG neurons, suggesting differences
      between these two groups. PAR2 signaling plays a role in this action and this
      protease signaling pathway could provide novel biomarkers and therapeutic targets
      for treatment.

PMID- 23958522
TI  - Functional characterization of fibrinolytic metalloproteinases (colombienases)
      isolated from Bothrops colombiensis venom.
AB  - Researchers trying to improve the safety and efficacy of fibrinolytic therapy
      have been isolating fibrinolytic enzymes from snake venoms. Two fibrinolytic
      enzymes, colombienases 1 and 2, with significant activity have been isolated from
      the venom of Bothrops colombiensis. METHODS: The colombienases were characterized
      for various biological activities which include hemorrhagic, fibrinogenolytic,
      proteolytic, hemolytic, edematogenic and cytotoxic. RESULTS: Colombienases
      directly acted on fibrin by degrading fibrinogen Aalpha and Bbeta chains without
      activating the fibrinolytic system (plasminogen/plasmin), additionally
      colombienase-2 degraded fibrinogen gamma chains as well as the fibronectin
      molecule. Laminin and type IV collagen were colombienases resistant. Gelatin
      zymogram activity was present in B. colombiensis venom (BcV) bands between 64 and
      148 kDa. All activities were abolished by metalloproteinases inhibitors. Both
      enzymes lacked hemorrhagic, hemolytic, cytotoxic, plasminogen activator and
      coagulant activities. CONCLUSIONS: Both colombienases had direct
      fibrino(geno)lytic activity without other toxic side effects including in vivo
      hemorrhaging, which could be promising in terms of therapeutic potential as
      thrombolytic agents.

PMID- 23958523
TI  - Voltammetric and impedimetric DNA detection at single-use graphite electrodes
      modified with gold nanorods.
AB  - In this study, single-use pencil graphite electrodes (PGEs) were modified by gold
      nanorods (AuNRs) and then single stranded oligonucleotide probe molecules
      (ssODNs) were immobilized onto the surface of AuNRs modified PGE. The
      electrochemical characterizations using electrochemical impedance spectroscopy
      (EIS) and cyclic voltammetry (CV) techniques were firstly performed to present
      the successfull modification of AuNR onto PGE surface. Under the optimum
      experimental conditions based on enhanced sensor response, single stranded thiol
      linked DNA probe ssODNs was immobilized onto AuNR modified PGE and accordingly, a
      sequence-selective DNA hybridization related to Hepatitis B virus (HBV) DNA was
      performed at the surface of AuNR modified electrodes. The impedimetric sequence
      selective HBV DNA hybridization was then explored in the case of complementary
      (target), or noncomplementary (NC) DNA sequences. 

PMID- 23958524
TI  - Implementing an acuity-adaptable care model in a rural hospital setting.
AB  - OBJECTIVE: This study examined the effects of an acuity-adaptable care model in a
      rural hospital setting on nurse satisfaction, patient satisfaction, patient
      safety, and quality indicators (events, falls, and medication errors), patient
      length of stay (LOS), and worked hours per patient-day (WHPPD). BACKGROUND:
      Acuity-adaptable care models have been implemented as a nursing strategy to
      improve workflow through the elimination of unit-to-unit patient handoffs.
      However, to our knowledge, this model of care has not been studied in a rural
      hospital setting. METHODS: A descriptive, comparative design with repeated
      measures was utilized for this study. A professional nurse survey was created to
      measure staff satisfaction; separate t tests for percentages were utilized to
      evaluate patient satisfaction and patient safety/quality indicators. Financial
      data were examined to perform the analysis of patient LOS and WHPPD. RESULTS: The
      nurse satisfaction survey demonstrated a decrease in weekly floating and
      cancellations due to low census. There was a statistically significant
      improvement in patient satisfaction for overall rating and willingness to
      recommend the hospital. No significant difference was noted in patient quality
      indicators or LOS; however, there was a favorable trend for all events and
      medication errors. This study also found a decrease in WHPPD, with a
      corresponding salary expense reduction reported. CONCLUSION: Acuity-adaptable
      units may be a viable strategy for rural facilities.

PMID- 23958525
TI  - 1-year retention rates and performance ratings: comparing associate degree,
      baccalaureate, and accelerated baccalaureate degree nurses.
AB  - The purpose of this study was to examine 1-year retention and managerial
      performance ratings of newly licensed RNs (NLRNs) according to nursing education
      program types (associate degree, traditional baccalaureate, and accelerated 2nd
      degree baccalaureate). Findings revealed retention and performance differences,
      suggesting the possibility of tradeoffs related to educational program type when
      selecting NLRNs for open positions. 

PMID- 23958527
TI  - Ringless alfieri mitral valve repair for significant ischemic mitral
      regurgitation with coronary artery bypass grafting.
AB  - BACKGROUND: Ischemic mitral regurgitation (IMR) is associated with diminished
      survival prospects. Ringless edge-to-edge mitral valve repair is usually
      performed in association with coronary artery bypass grafting (CABG). In this
      report, we present our early results for ringless edge-to-edge repair and
      concomitant CABG. METHODS: Between January 2011 and June 2012, 17 patients
      underwent ringless edge-to-edge mitral valve repair. The cause was ischemic in
      all patients. A double-orifice repair was done in all patients. Complete coronary
      revascularization was routinely added in all cases. RESULTS: There were no
      hospital and late deaths. Low cardiac output developed in 5 patients (29.41%) and
      was treated with inotropic agents. Two of these patients required intraaortic
      balloon pump support. Atrial fibrillation and ventricular arrhythmia developed in
      5 (29.41%) of the patients, and all of them converted to sinus rhythm with
      antiarrhythmic agents. The mean (SD) stays in the intensive care unit and the
      hospital were 2.83 +/- 1.29 days and 7.74 +/- 2.14 days, respectively. As of the
      latest follow-up, all patients were in New York Heart Association class I or II.
      There was no recurrent mitral valve regurgitation or valve-related complications.
      CONCLUSIONS: Alfieri mitral valve repair is associated with lower risks of
      mortality, postoperative stroke, and prolonged intensive care unit and hospital
      stays. Alfieri mitral valve repair and concomitant CABG surgery can be performed
      in patients with IMR.

PMID- 23958526
TI  - Comparison of conventional and no-touch techniques in harvesting saphenous vein
      for coronary artery bypass grafting in view of endothelial damage.
AB  - BACKGROUND: Optimization of saphenous vein patency for myocardial
      revascularization. OBJECTIVE: The goal of this study was to present the no-touch
      technique of saphenous vein preparation. This technique consists of harvesting
      the vein with a pedicle of surrounding tissue, which protects the vein from
      distension pressure. METHODS: We performed a prospective, randomized study that
      compared 2 techniques for harvesting saphenous vein-conventional and no-touchin
      40 patients undergoing coronary artery bypass grafting. We carried out a
      morphologic study of the endothelium with the aid of light and transmission
      electron microscopy and an immunohistochemical assessment to identify adenosine,
      inducible nitric oxide synthase (iNOS), and vascular endothelial growth factor
      (VEGF) in the vein wall. RESULTS: The integrity of endothelial cell and all
      vascular layers was maintained better with the no-touch technique than with the
      conventional procedure. The immunohistochemical assessment revealed that
      adenosine receptor, iNOS, and VEGF immunoexpression levels were normal or lower
      in the no-touch group than in the conventional-harvest group, as shown by the
      staining densities in all layers of the vein wall. CONCLUSION: Endothelial
      integrity and adenosine, iNOS, and VEGF immunoreactivities were better preserved
      when the no-touch technique was used for vein graft harvesting. The mechanical
      protection provided by the cushion of surrounding tissue in the no-touch group
      and the vasorelaxation and thromboresistant activities of nitric oxide may be
      responsible for the reduction in vasospasms and the improved patency rate.

PMID- 23958528
TI  - Repair of rheumatic tricuspid valve stenosis with autologous pericardium.
AB  - The aim of the present study was to describe a successful method for treating
      rheumatic tricuspid valve stenosis with autologous pericardium, commissurotomy,
      and a Kalangos ring without replacing the tricuspid valve. 

PMID- 23958529
TI  - Is percutaneous transluminal coronary angioplasty the treatment of choice for
      iatrogenic stenosis of the left main coronary artery following aortic valve
      replacement?
AB  - Iatrogenic coronary ostial stenosis after aortic valve replacement (AVR) is a
      rare but life-threatening complication. This condition has been treated with
      urgent coronary bypass surgery, but such surgery is associated with high
      morbidity and mortality. The clinical symptoms are usually severe and may appear
      from 1 to 6 months postoperatively. Pains in the chest that are typical for
      coronary artery disease but occur in patients after the AVR operation suggest a
      significant threat. We report a case of left main coronary artery ostial stenosis
      in a patient who had normal preoperative coronary angiography results. The
      patient was successfully treated with implantation of a drug-eluting stent. 

PMID- 23958530
TI  - Device size for transcatheter closure of ovoid interatrial septal defect.
AB  - BACKGROUND: For successful transcatheter closure of an atrial septal defect with
      the Amplatzer septal occluder, the shape of the defect should be considered
      before selecting the device size. The purpose of this study was to evaluate the
      results of transcatheter closure of an ovoid atrial septal defect. METHODS:
      Between January 2010 and February 2012, cardiac computer tomography examinations
      were performed in 78 patients who subsequently underwent transcatheter closure of
      an atrial septal defect. In this retrospective study, we reviewed these patients'
      medical records. We defined an ovoid atrial septal defect as a value of 0.75 for
      the ratio of the shortest diameter of the defect to the longest diameter, as
      measured in a computed tomography image. Transthoracic echocardiography
      examinations were made at 1 day and 6 months after the procedure. RESULTS:
      Transcatheter closure of an atrial septal defect was successful in 26 patients in
      the ovoid-defect group and in 52 patients in the round-defect group. There were
      no serious complications in either group, and the rate of complete closure at 6
      months was 92.3% in the ovoid-defect group and 93.1% in the round-defect group (P
      > .05). The mean (SD) difference between the device size and the defect's longest
      diameter, and the mean ratio of the device size to the longest diameter were
      significantly smaller in the ovoid-defect group (1.7 +/- 2.9 versus 3.8 +/- 2.5
      and 1.1 +/- 0.1 versus 1.3 +/- 0.2, respectively). CONCLUSIONS: Transcatheter
      closure of an atrial septal defect is indicated even for an ovoid atrial septal
      defect. Ovoid atrial septal defects can be closed successfully with smaller sizes
      of the Amplatzer septal occluder than for round atrial septal defects.

PMID- 23958531
TI  - The prevalence and extent of coronary atherosclerosis among patients with a zero
      calcium score and the influence of patient characteristics.
AB  - PURPOSE: Coronary artery calcium (CAC) is a specific indicator of and an
      independent risk factor for atherosclerosis; however, calcium scoring may miss
      noncalcified plaques, which may have clinical importance. The aim of this study
      was both to identify the presence and extent of coronary plaques during computed
      tomography coronary angiography (CTCA) in patients with a zero CAC score and to
      evaluate the effect of risk factors and symptom status on the presence of
      noncalcified plaques. MATERIALS AND METHODS: In this retrospective study, we
      analyzed the cases of 842 consecutive patients between October 2006 and November
      2011. Of these patients, we included 357 with a zero calcium score in the study.
      Information regarding patient age, sex, coronary risk factors, and symptom status
      were recorded. Coronary calcium-scoring scans were followed by CTCA. The calcium
      scores were calculated, and the presence of noncalcified plaques and significant
      stenoses (>50% of vessel diameter) was evaluated. RESULTS: Of the 357 patients
      with a zero calcium score, 37 (10.36%) had atherosclerotic plaques; 9 patients
      (2.52%) had significant coronary stenosis. Among coronary risk factors, only
      diabetes mellitus was significantly correlated with any risk factors (presence of
      atherosclerosis and obstructive coronary artery disease; P = .030 and .013,
      respectively). CONCLUSION: Although CAC scoring is a safe and a reliable test to
      exclude obstructive coronary artery disease, the absence of CAC does not
      definitively exclude the presence of atherosclerosis. CTCA is a more appropriate
      method for determining the atheroma burden.

PMID- 23958532
TI  - Recombinant activated factor VII administration after pulmonary embolectomy: case
      report.
AB  - Bleeding management in cardiac surgery could be a great challenge for the surgeon
      and a life-threatening moment for the patient. Despite the fact that recombinant
      activated factor VII is now widely accepted as a useful adjunct in the management
      of postcardiotomy coagulopathy, its use in the course of recent thromboembolic
      event is rarely described. We hereby present a case of rescue recombinant
      activated factor VII administration to manage a severe coagulation disorder
      during surgical pulmonary embolectomy performed under cardiopulmonary bypass. 

PMID- 23958533
TI  - Successful treatment of ulcerative colitis-related fulminant myocarditis using
      extracorporeal life support.
AB  - Myocarditis is a known extraintestinal manifestation of inflammatory bowel
      diseases, but it rarely leads to acute cardiac pump failure. We report a case of
      fulminant myocarditis associated with ulcerative colitis treated successfully
      with an extracorporeal membrane oxygenator. 

PMID- 23958534
TI  - Repair of anomalous left coronary artery from pulmonary artery (ALCAPA) beyond
      infancy.
AB  - Between January 2002 and December 2012, five patients (4 female) underwent
      corrective surgery for anomalous left coronary artery from pulmonary artery
      (ALCAPA). They were older than 1 year (range, 3-56 years). One of the 2 patients
      younger than 10 years had presented with congestive heart failure, and the other
      had experienced repeated episodes of lower respiratory tract infection since
      childhood. Of the remaining 3 adult patients, 2 had experienced angina with
      effort, and 1 patient had had repeated respiratory tract infections since
      childhood, with mild dyspnea on effort of New York Heart Association (NYHA) class
      II. Three patients had the anomalous left coronary artery implanted directly into
      the ascending aorta via coronary-button transfer, and 2 patients underwent
      coronary artery bypass with obliteration of the left main ostium. Two patients
      underwent concomitant mitral valve repair procedures, and 1 patient underwent
      direct closure of a perimembranous ventricular septal defect. Four patients
      survived the surgery, and 1 patient died because of a persistently low cardiac
      output. Follow-up times ranged from 3 months to 4 years. All survivors are in
      NYHA class I and have left ventricular ejection fractions of 45% to 60%, with
      moderate (n = 1), mild (n = 1), or no (n = 2) mitral insufficiency. We conclude
      that a few naturally selected patients with ALCAPA do survive beyond infancy and
      can undergo establishment of 2 coronary systems with satisfactory results. 

PMID- 23958535
TI  - Incidental gossypiboma discovered during tricuspid valve re-repair 11 years after
      Ebstein anomaly repair.
AB  - BACKGROUND: A retained surgical sponge, an extremely rare occurrence after
      cardiac surgery, can trigger a granulomatous reaction and form a sizeable mass or
      gossypiboma. We report the incidental operative finding of a gossypiboma 11 years
      after repair of Ebstein anomaly. CASE REPORT: A 24-year-old man, who had
      previously undergone tricuspid annuloplasty for Ebstein anomaly 11 years earlier
      at another institution, was referred for recurrent severe tricuspid
      regurgitation. During the dissection along the superior vena cava and the right
      atrium, we entered 2 cystic cavities that exuded a pus-like material, which was
      sent for culture. Mesh from a retained surgical sponge (gossypiboma) was
      identified. After complete debridement and administration of vancomycin, the
      tricuspid valve was repaired. Antibiotics were continued until culture results
      were confirmed to be negative. The patient's postoperative course was uneventful,
      and he presented no signs of infection. CONCLUSIONS: We report a rare case of
      incidentally found gossypiboma after cardiac surgery.

PMID- 23958536
TI  - Progression of aortic regurgitation in Asian patients with congenital sinus of
      valsalva aneurysm.
AB  - BACKGROUND: We reviewed the experience of An Zhen and Fu Wai Hospital for
      congenital sinus of Valsalva aneurysm (SVA) to determine risk factors for aortic
      valve replacement (AVR) and postoperative progression of aortic regurgitation
      (AR). METHODS: Over a 7-year period, 255 patients underwent surgical repair of an
      SVA. Aneurysms originated from the right sinus and the noncoronary sinus in 212
      patients (83.1%) and 38 patients (14.9%), respectively, and protruded into the
      right ventricle and right atrium in 171 patients (67.1%) and 80 patients (31.4%),
      respectively. AR presented in 142 patients (55.7%), 60 patients underwent AVR,
      and 13 patients underwent aortic valvuloplasty (3 patients eventually received
      AVR for valvuloplasty failure). RESULTS: All patients survived the operation.
      Late death occurred in 2 patients (0.8%), and 2 patients (0.8%) experienced
      anticoagulation-related complications. Logistic regression analysis revealed that
      infective endocarditis, the cardiothoracic ratio, and a nonruptured SVA were risk
      factors for AVR. Late follow-up of 150 patients by echocardiographic assessment
      revealed that AR improved in 17 patients and worsened in 20 patients. Cox
      regression analysis revealed AR at discharge to be an independent risk factor for
      AR aggravation at late follow-up. CONCLUSIONS: SVA can be repaired with low
      mortality and excellent long-term results. AR at discharge is an important factor
      in determining AR aggravation at late follow-up after the operation. We recommend
      early diagnosis and aggressive treatment for SVA.

PMID- 23958537
TI  - A case series of a hybrid approach to aortic arch disease.
AB  - OBJECTIVE: Debranching of the aortic arch and endovascular stent placement as a
      combination therapy for complex aortic arch pathology has emerged over the past
      few years as an alternative to traditional repair. This hybrid approach is a
      viable option for patients who would not tolerate conventional arch replacement,
      as well as for patients with a failed stent graft of the descending aorta and a
      subsequent type I endoleak. METHODS: We retrospectively reviewed the preoperative
      characteristics and postoperative outcomes of 5 patients who underwent
      debranching of the aortic arch and implantation of an endovascular stent across
      the aortic arch between 2008 and 2011. Data were analyzed with the Student t test
      and the Kaplan-Meyer method. RESULTS: The mean age was 70.6 +/- 18 years; 4 men
      and 1 woman were evaluated. One patient had previous aortic surgery for
      dissection. The preoperative morbidities included arrhythmia (1 patient), chronic
      obstructive pulmonary disease (2 patients), cerebrovascular accident (1 patient),
      diabetes mellitus (2 patients), coronary artery disease (2 patients), and active
      angina (1 patient). One patient had a myocardial infarction 3 weeks before
      surgery. The primary technical-success rate was 100%, and none of the patients
      died in the perioperative phase. The mean follow-up time was 22 +/- 18.4 months,
      and the median follow-up time was 13.8 months (range, 7.13-50.7 months). Two
      patients died during follow-up. The pathology of the aorta in the patients who
      died was arch aneurysm; the 3 remaining patients are alive and regularly followed
      at our institution. CONCLUSION: The combination of surgery and simultaneous
      endovascular stenting in the operating room is an alternative approach for
      patients who are poor candidates for traditional arch repair under circulatory
      arrest.

PMID- 23958538
TI  - Does oral hygiene trigger carotid artery intima-media thickness?
AB  - BACKGROUND AND PURPOSE: The aim of this study was to evaluate whether poor oral
      hygiene is associated with the intima-media thickness of the carotid arteries,
      which is one of the predictors of future progression of subclinical
      atherosclerosis. METHODS: We selected 108 patients during periodontal
      examinations according to their oral hygiene. The patients had no history of
      atherosclerotic disease. The results of carotid artery B-mode ultrasonography
      examinations were analyzed at baseline and after a mean of 7.8 months. Patients
      were scored on the DMFT index for the number of decayed (D), missing (M), and
      filled (F) teeth (T). We also used the Silness-Loe plaque index (SLI) to evaluate
      oral hygiene and dental plaque. The patients were divided into 2 groups according
      to DMFT and SLI criteria. Group I had a DMFT index of 0 to 3 and an SLI score of
      0 or 1; group II had a DMFT index of 4 to 28 and an SLI score of 2 or 3. RESULTS:
      Dental status and oral hygiene were significantly associated with carotid artery
      intima-media thickness. Patients with increasing DMFT and SLI indices were
      correlated with intima-media thickness of the carotid artery. CONCLUSIONS:
      Chronic poor oral hygiene and tooth loss are related to subclinical
      atherosclerotic changes in the carotid arteries and might be indicative of future
      progression of atherosclerosis.

PMID- 23958539
TI  - Coronary artery occlusion after cardiac transplantation.

PMID- 23958540
TI  - Linaclotide inhibits colonic nociceptors and relieves abdominal pain via
      guanylate cyclase-C and extracellular cyclic guanosine 3',5'-monophosphate.
AB  - BACKGROUND & AIMS: Linaclotide is a minimally absorbed agonist of guanylate
      cyclase-C (GUCY2C or GC-C) that reduces symptoms associated with irritable bowel
      syndrome with constipation (IBS-C). Little is known about the mechanism by which
      linaclotide reduces abdominal pain in patients with IBS-C. METHODS: We determined
      the effects of linaclotide on colonic sensory afferents in healthy mice and those
      with chronic visceral hypersensitivity. We assessed pain transmission by
      measuring activation of dorsal horn neurons in the spinal cord in response to
      noxious colorectal distention. Levels of Gucy2c messenger RNA were measured in
      tissues from mice using quantitative reverse transcription polymerase chain
      reaction and in situ hybridization. We used human intestinal cell lines to
      measure release of cyclic guanosine-3',5'-monophosphate (cGMP) by linaclotide. We
      performed a post-hoc analysis of data from a phase III, double-blind, parallel
      group study in which 805 patients with IBS-C were randomly assigned to groups
      given an oral placebo or 290 MUg linaclotide once daily for 26 weeks. We
      quantified changes in IBS-C symptoms, including abdominal pain. RESULTS: In mice,
      linaclotide inhibited colonic nociceptors with greater efficacy during chronic
      visceral hypersensitivity. Intra-colonic administration of linaclotide reduced
      signaling of noxious colorectal distention to the spinal cord. The colonic
      mucosa, but not neurons, was found to express linaclotide's target, GC-C. The
      downstream effector of GC-C, cGMP, was released after administration of
      linaclotide and also inhibited nociceptors. The effects of linaclotide were lost
      in Gucy2c(-/-) mice and prevented by inhibiting cGMP transporters or removing the
      mucosa. During 26 weeks of linaclotide administration, a significantly greater
      percentage of patients (70%) had at least a 30% reduction in abdominal pain
      compared with patients given placebo (50%). CONCLUSIONS: We have identified an
      analgesic mechanism of linaclotide: it activates GC-C expressed on mucosal
      epithelial cells, resulting in the production and release of cGMP. This
      extracellular cGMP acts on and inhibits nociceptors, thereby reducing
      nociception. We also found that linaclotide reduces chronic abdominal pain in
      patients with IBS-C.

PMID- 23958542
TI  - Tumor stem cells (CD271, c-kit, SOX10) in Melanomas: prognostic and outcome
      implications.
AB  - Melanoma cells that express stem cell marker CD271 are shown to form tumors when
      transplanted into nude or immunodeficient mice. These tumors have a higher
      metastatic potential and worse prognosis than melanomas resulting from
      transplantation of CD271-negative cells. We studied stem cell markers (CD271, c
      kit, SOX1O) in melanomas, correlating their presence with prognostic factors and
      outcome. A total of 82 melanomas in tissue microarrays were immunostained for
      CD271, c-kit, and SOX10. Results were correlated with clinicopathologic
      prognostic parameters (Breslow depth of invasion, Clark level, sentinel lymph
      node status, and pathologic stage) and outcome (recurrence, metastases, and
      death). Of the 82 melanomas, CD271 was expressed in 18 (21%), c-kit in 47 (57%),
      and SOX10 in all (100%). CD271 does show correlation with metastases (P=0.05). c
      kit is associated with favorable prognostic parameters [Breslow depth (P<0.001)
      and pathologic stage (P=0.02)] and with improved outcome [recurrence (P=0.03) and
      metastases (P=0.004)]. Although SOX10 is a good diagnostic marker, it cannot be
      used for prognosis because it is expressed in all the melanomas studied. In
      conclusion, CD271 expression in melanomas is associated with increased frequency
      of metastases, and c-kit immunoreactivity is associated with favorable prognostic
      parameters and improved outcome. 

PMID- 23958541
TI  - A high-fat diet activates oncogenic Kras and COX2 to induce development of
      pancreatic ductal adenocarcinoma in mice.
AB  - BACKGROUND & AIMS: Obesity is a risk factor for pancreatic ductal adenocarcinoma
      (PDAC), but it is not clear how obesity contributes to pancreatic carcinogenesis.
      The oncogenic form of KRAS is expressed during early stages of PDAC development
      and is detected in almost all of these tumors. However, there is evidence that
      mutant KRAS requires an additional stimulus to activate its full oncogenic
      activity and that this stimulus involves the inflammatory response. We
      investigated whether the inflammation induced by a high-fat diet, and the
      accompanying up-regulation of cyclooxygenase-2 (COX2), increases Kras activity
      during pancreatic carcinogenesis in mice. METHODS: We studied mice with acinar
      cell-specific expression of KrasG12D (LSL-Kras/Ela-CreERT mice) alone or crossed
      with COX2 conditional knockout mice (COXKO/LSL-Kras/Ela-CreERT). We also studied
      LSL-Kras/PDX1-Cre mice. All mice were fed isocaloric diets with different amounts
      of fat, and a COX2 inhibitor was administered to some LSL-Kras/Ela-CreERT mice.
      Pancreata were collected from mice and analyzed for Kras activity, levels of
      phosphorylated extracellular-regulated kinase, inflammation, fibrosis, pancreatic
      intraepithelial neoplasia (PanIN), and PDACs. RESULTS: Pancreatic tissues from
      LSL-Kras/Ela-CreERT mice fed high-fat diets (HFDs) had increased Kras activity,
      fibrotic stroma, and numbers of PanINs and PDACs than LSL-Kras/Ela-CreERT mice
      fed control diets; the mice fed the HFDs also had shorter survival times than
      mice fed control diets. Administration of a COX2 inhibitor to LSL-Kras/Ela-CreERT
      mice prevented these effects of HFDs. We also observed a significant reduction in
      survival times of mice fed HFDs. COXKO/LSL-Kras/Ela-CreERT mice fed HFDs had no
      evidence for increased numbers of PanIN lesions, inflammation, or fibrosis, as
      opposed to the increases observed in LSL-Kras/Ela-CreERT mice fed HFDs.
      CONCLUSIONS: In mice, an HFD can activate oncogenic Kras via COX2, leading to
      pancreatic inflammation and fibrosis and development of PanINs and PDAC. This
      mechanism might be involved in the association between risk for PDAC and HFDs.

PMID- 23958543
TI  - How to identify patients with increased risk of breast cancer relapse?
AB  - A cohort of 362 breast cancer patients had subtype classification accomplished
      using 4 immunohistochemical markers: luminal A (ER or PR positive, HER2 negative,
      Ki-67<14%), luminal B (ER or PR positive, HER2 negative, Ki-67>=14%), luminal
      HER2 (ER or PR positive, HER2 positive), HER2 enriched (ER or PR negative, HER2
      positive) or triple negative (ER, PR, and HER2 negative). Multivariable Cox
      analysis was used to determine the risk of local (LR) or distant (DR) relapse
      associated with the intrinsic subtypes, adjusting for standard clinicopathologic
      factors. There have been a total of 124 recurrences. Triple-negative patients
      were associated with increased risk of LR. Luminal B subtype showed statistical
      tendency (P=0.053) to LR. For patients undergoing breast conservation surgery,
      luminal B and HER2-enriched subtypes demonstrated an increased risk to LR, and
      this was statistically significant on multivariable analysis. After mastectomy,
      there was no statistical difference between subtypes of LR or DR on multivariable
      analysis. Luminal A tumors are associated with a low risk of LR or DR. Despite
      the existence of gene expression profiling, in the current study we demonstrate
      that analysis of 4 immunohistochemical markers is equally effective and less
      expensive alternative to identify higher recurrence risk patients. 

PMID- 23958544
TI  - Expression of gastrin-releasing peptide receptor in epidermoid carcinoma of the
      anal canal.
AB  - Gastrin-releasing peptide is a neuroendocrine homolog of bombesin that
      demonstrated important growth-stimulatory effects in various types of cancer.
      High levels of expression of gastrin-releasing peptide receptors (GRPR) has been
      found in different malignancies, and the studies exploring the therapeutic use of
      GRPR antagonists have shown promising results. Our aim was to determine the GRPR
      expression in epidermoid carcinoma of the anal canal and discuss its potential
      clinical applications. We performed immunohistochemical analysis for GRPR on
      formalin-fixed and paraffin-embedded tumor samples obtained from 35 patients with
      anal cancer. As a control group, we analyzed 24 samples of nonmalignant anal
      tissues (hemorrhoidectomy specimens). GRPR expression was evaluated using a
      semiquantitative approach according to the intensity and distribution of
      staining. All analyzed tissues, except 1 control sample, showed positive GRPR
      immunoexpression. GRPR was strongly expressed in 54% of cancer specimens as
      compared with only 12% of the control specimens (P<0.003). In tumors, the
      receptor showed a diffuse and homogenous pattern of distribution within the
      specimens. In contrast, control specimens showed a focal pattern of staining
      restricted to the basal half of the epithelium. In conclusion, we demonstrated
      that GRPR is highly expressed in epidermoid carcinoma of the anal canal,
      suggesting this receptor might have a role in anal carcinogenesis. Our results
      provide a basis for exploiting GRPR as a target for diagnostic and therapeutic
      purposes in the anal cancer.

PMID- 23958545
TI  - The prognostic importance of nuclear factor kappaB and hypoxia-inducible factor
      1alpha in relation to the breast cancer subtype and the overall survival.
AB  - Breast cancer shows extensive clinical and molecular heterogeneity. Prognostic
      factors are very important for outcome estimation in individual patients. Nuclear
      factor kappaB (NF-kappaB) and hypoxia-inducible factor 1alpha (HIF-1alpha) are
      transcriptional factors involved in cancerogenesis and in the metastatic spread
      of tumor cells. The aim of this study was to evaluate the expression of NF-kappaB
      and HIF-1alpha and to correlate the immunohistochemical expression of these
      markers with the breast cancer subtype and the patient outcome. The retrospective
      study included 208 cases of ductal invasive breast cancers stratified by the
      molecular subtype according to the St. Gallen 2011 classification. The Kaplan
      Meier survival curve showed that an increased mortality risk was associated with
      tumors belonging not to the luminal A subtypes but to the Her-2-enriched and
      luminal B-Her-2-positive subtypes instead (P<0.001). Activation of NF-kappaB was
      associated with estrogen-negative tumors (P=0.005). We found a better overall
      survival in NF-kappaB-positive tumors in the luminal A subtype (P=0.021). This
      may be explained as a consequence of a possible tumor-suppressing effect of NF
      kappaB. HIF-1alpha was related to the overall survival as a poor prognostic
      factor (P=0.036). In our opinion, the practical relevance of NF-kappaB and HIF
      1alpha expression as prognostic indicators and potential targets for specific
      therapies deserve further investigation.

PMID- 23958546
TI  - Histologic variants of seminoma mimicking lymphatic malignancies of the testis: a
      literature review with a report of case series focusing on problems in
      differential diagnosis.
AB  - We focused on the clinical and morphologic similarities that may cause a
      misdiagnosis between histologic variants of seminoma and we highlighted the
      differences between spermatocytic seminoma and high-mitotic rate seminoma or
      plasmocytic testicular lymphoma or plasmacytoma of the testis. We emphasized on
      the difficult points in the differential diagnosis, with a critical review of the
      literature, reporting a case series to discuss problems in differential
      diagnosis. 

PMID- 23958547
TI  - Expression of REG4 in ovarian mucinous tumors.
AB  - Regenerating islet-deprived gene family, number 4 (REG4), is a novel marker for
      intestinal differentiation. We performed immunohistochemical studies on REG4,
      cytokeratin (CK)7, CK20, and caudal type homeobox 2 (CDX2) in 291 ovarian
      mucinous tumors. There were 226 primary tumors and 65 metastatic tumors. The
      primary tumors comprised 69/226 mucinous cystadenomas, 79/226 mucinous borderline
      tumors (64/79 intestinal-type and 15/79 endocervical-like tumors), and 78/226
      mucinous carcinomas. We found that REG4 expression was significantly higher in
      mucinous borderline tumors (30/79, 38.0%) and primary mucinous carcinomas (26/78,
      33.3%) than in mucinous cystadenomas (4/69, 5.8%; P<0.05). However, REG4
      expression was more commonly associated with intestinal-type, borderline,
      mucinous tumors rather than the endocervical-like type (30/64 vs. 0/15, P<0.001).
      There was a significant correlation between the REG4 and CDX2 expression profiles
      in primary ovarian mucinous tumors (r=0.772, P<0.001). REG4, CDX2, and diffuse
      CK20 had higher expression frequencies in metastatic lower gastrointestinal
      adenocarcinoma than in primary mucinous tumors (P<0.01). The CK7/REG4 coordinate
      expression profile was comparable in diagnostic value to CK7/CK20 or CK7/CDX2
      profile. We conclude that REG4 expression is common in mucinous borderline tumors
      of the intestinal type as it is absent in the endocervical-like form in this
      series. Expression of CK7/REG4 may contribute to the differential diagnosis
      between primary and metastatic ovarian mucinous tumors. 

PMID- 23958548
TI  - Diagnostic utility of PLAG1 immunohistochemical determination in salivary gland
      tumors.
AB  - PLAG1 (pleomorphic adenoma gene 1) is a proto-oncogene whose overexpression is a
      crucial oncogenic event in salivary gland pleomorphic adenomas (PA), and in
      carcinoma ex-PA. The aim of the present study is to evaluate the sensitivity and
      the specificity of PLAG1 as a marker in the differential diagnosis of salivary
      gland benign and malignant tumors. We examined 101 cases, including 36 PAs, 8
      myoepitheliomas, 3 basal cell adenomas, and 1 canalicular adenoma among benign
      tumors; 16 mucoepidermoid carcinomas, 10 adenoid cystic carcinomas, 8 acinic cell
      carcinomas, 8 polymorphous low-grade adenocarcinomas, 7 salivary duct carcinoma,
      and 4 epithelial-myoepithelial carcinoma among malignant tumors. PLAG1 was
      diffusely positive in 94.4% of PAs and in all myoepitheliomas, although with a
      lower staining intensity. Among malignant tumors, 2 (25%) polymorphous low-grade
      adenocarcinomas and 1 salivary duct carcinoma ex-PA were positive. In conclusion,
      PLAG1 is a marker with good specificity for PA and could be a useful diagnostic
      adjunct in the diagnosis of salivary gland tumors. In particular, this marker is
      negative in the most common salivary carcinomas, including adenoid cystic
      carcinoma, mucoepidermoid carcinoma, and acinic cell carcinoma. However, some
      mimickers of PA, like polymorphous low-grade adenocarcinoma, may show occasional
      positivity for PLAG1, thus limiting its diagnostic use. In addition, carcinoma ex
      PA shows consistent positivity, and therefore should be considered as a
      diagnostic possibility in case of a malignant tumor with PLAG1 expression. 

PMID- 23958549
TI  - Mammaglobin-A immunohistochemistry in primary central nervous system neoplasms
      and intracranial metastatic breast carcinoma.
AB  - Metastases represent the most common type of intracranial neoplasm. In women, 30%
      of such tumors derive from breast carcinoma. In neurosurgical cases with
      ambiguous cellular morphology and/or limited biopsy material,
      immunohistochemistry (IHC) is often performed to distinguish metastases from
      primary central nervous system (CNS) neoplasms. IHC for mammaglobin-A (MGA), a
      protein expressed in a majority of breast carcinomas, is commonly applied in this
      setting, but its utility for distinguishing primary CNS neoplasms from metastatic
      breast carcinoma is unknown; the reactivity of MGA in primary and metastatic CNS
      neoplasms has never been described. Here, we describe the frequency and patterns
      of IHC reactivity for MGA in metastatic and primary CNS neoplasms from patients
      with well-documented histories of breast carcinoma. Following a published
      protocol previously applied to non-CNS neoplasms, MGA staining of moderate to
      strong intensity within 5% or more of a neoplasm was considered positive. On the
      basis of these criteria, 3 of 12 (25.0%) glioblastomas, 1 of 10 (10.0%)
      meningiomas, and 47 of 95 (49.5%) metastases were positive. Importantly, the
      cytoarchitectural staining characteristics among all 4 MGA-positive primary CNS
      neoplasms (cytoplasmic and nuclear) differed from those of the metastases
      (cytoplasmic and membranous). These findings suggest that MGA IHC staining
      intensity and distribution can distinguish metastases from primary CNS neoplasms
      (P=0.0086) in women with a history of breast carcinoma but also indicate that
      cytologic staining patterns must be interpreted for more accurate tumor
      classification.

PMID- 23958550
TI  - AngioMap is a novel image analysis algorithm for assessment of plasma cell
      distribution within bone marrow vascular niche.
AB  - The ability to characterize distribution of neoplastic hematopoietic cells and
      their progenitors in their native microenvironment is emerging as an important
      challenge and potential therapeutic target in many disease areas, including
      multiple myeloma. In multiple myeloma, bone marrow (BM) angiogenesis is typically
      increased and microvessel density is a known indicator of poor prognosis.
      However, the difficulty of consistently measuring 3D vessels from 2D cut sections
      has previously limited the study of spatial distribution of plasma cells (PC) and
      their interaction with BM microenvironment. The aim of the study is to report a
      novel method to study myeloma cells spatial distribution within their
      hematopoietic niche context using readily available tissue sections and standard
      histology approaches. We utilized a novel whole-tissue image analysis approach to
      identify vessels, and then applied computational grown regions extended out from
      each vessel at 15, 35, 55, 75, and 100 MUm to identify the spatial distribution
      of PC on CD34/CD138 double-stained core biopsy slides. Percent PC to total cells
      (TC) was significantly higher at <15 MUm distance compared with those at 16 to
      35, 36 to 55, 56 to 75, and 76 to 100 MUm distance (P=0.0001). Similarly, PC/TC
      at <35 MUm region was significantly higher compared with 36 to 55 (P=0.0001), 56
      to 75 (P<=0.0001), and 76 to 100 (P=0.0002) MUm distances. The mean PC/TC
      differences in the spatial gradient of 36 to 55, 56 to 75, and 76 to 100 MUm
      distance regions were not significant. Our findings suggest possible preferential
      advantage to neoplastic PC in the proximity of blood vessels compared with other
      hematopoietic marrow cells. We demonstrate the feasibility of analyzing the
      spatial distribution of PC, and possibly other hematopoietic/stem cells in their
      microenvironment, as characterized by the distance to vessels in BM using a novel
      image analysis approach. 

PMID- 23958551
TI  - In search of the ideal immunopanel to distinguish metastatic mammary carcinoma
      from primary lung carcinoma: a tissue microarray study of 207 cases.
AB  - BACKGROUND: Distinguishing metastatic carcinoma of breast origin (MCBO) to lung
      from primary lung carcinomas (PLC) is a diagnostic quandary with clinical
      ramifications. Immunostains CK7, CK20, ER, PR, and Mammaglobin as well as
      pertinent negative stains are utilized but prove insufficient. We set out to
      identify stains either alone or as a group that would better discern between
      these 2 entities. DESIGN: Tissue microarrays of 109 MCBO to lung and 102 PLC were
      stained with CK7, CK20, ER, PR, AR, Mammaglobin, Napsin A, GATA-3, and TTF-1. An
      H-score was calculated for each case and stain. RESULTS: The highest area under
      the receiver-operating characteristic curves for each stain was seen with GATA-3
      (0.817), Napsin A (0.817), and TTF-1 (0.854). When all possible combinations were
      analyzed, GATA-3 and TTF-1 proved to correctly classify with the highest accuracy
      (0.934). Combinations of GATA-3 and Napsin A (0.920) and GATA-3, Napsin A, and
      TTF-1 (0.933) were not significantly different from GATA-3 and TTF-1. The odds
      ratios for each stain and combination of stains showed that those for GATA-3 and
      TTF-1 were divergent, signifying that cases with higher H-scores for GATA-3 and
      TTF-1 were more likely to be classified as MCBO and PLC, respectively.
      CONCLUSIONS: GATA-3 and TTF-1 can correctly classify a case as either MCBO or PLC
      in 93.4% of cases. Although highly specific and sensitive for PLC, Napsin A in
      lieu of TTF-1 or as an additional stain did not improve classification accuracy.

PMID- 23958552
TI  - Role of PAX-8, CD5, and CD117 in distinguishing thymic carcinoma from poorly
      differentiated lung carcinoma.
AB  - AIM: To determine if PAX-8, CD5, and CD117 can differentiate thymic carcinoma
      from poorly differentiated lung carcinoma. DESIGN: Archived cases of thymic
      (n=13) and poorly differentiated lung (n=15) carcinoma were analyzed for
      intensity and proportion of expression of PAX-8, CD117, and CD5. RESULTS: PAX-8
      was positive in 69.2% of thymic and 5.8% of lung carcinomas. CD117 was positive
      in 84% of thymic and 26.6% of lung carcinomas. A total of 53% of thymic and none
      of the lung carcinomas were positive for CD5. Forty-six percent, 53%, and 69% of
      thymic carcinomas were dual positive for combinations of CD5/PAX-8, CD117/CD5,
      and CD117/PAX-8, respectively. None of the lung carcinomas were dual positive.
      Positivity for any 2 of the 3 markers was seen in 84% of thymic and none of the
      lung carcinomas. Triple positivity was seen in 53% of thymic carcinomas.
      CONCLUSION: Adding PAX-8 to CD117 and CD5 increases the diagnostic yield for
      thymic carcinoma.

PMID- 23958553
TI  - Novel Clonal t(2;4) (q23;p14) Secondary Cytogenetic Abnormality in a Primary
      Myxoid Liposarcoma.
AB  - Myxoid liposarcomas are malignant lipomatous tumors with a predilection for young
      adults. They are characterized by the presence of reciprocal translocation
      between the CHOP (DDIT3) gene on chromosome 12 and the FUS gene on chromosome 16,
      t(12;16)(q13;p11.2) in >95% of cases, or less commonly, a translocation between
      the DDIT3 and EWSR1 genes, t(12;22)(q13;q12). Secondary aberrations involving
      trisomy 8 and chromosomes 1 and 16 have been reported. Herein, we report for the
      first time a novel secondary clonal translocation, t(2;4) (q23;p14) in addition
      to t(12;16)(q13; p11.2) in a 30-year-old woman with myxoid liposarcoma on the
      left posterior thigh region without any prior chemoradiation therapy. The
      significance of this translocation remains to be established. 

PMID- 23958554
TI  - Epidemiology of paediatric minor head injury: Comparison of injury
      characteristics with Indices of Multiple Deprivation.
AB  - BACKGROUND: Head injury (HI) is a common presentation to Child Emergency
      Departments (CEDs), but the actual number of children attending with minor HI is
      unclear. Most research has focussed on admitted patients, often relying on
      hospital-coded admission data. We studied the incidence of minor HI presenting to
      the CED of a major teaching hospital in Coventry and Warwickshire. HI attendances
      were compared with population data to identify injury patterns relating to
      deprivation. METHODS: All CED admissions were screened by the research team, and
      data on minor head injuries (GCS 13-15) collected prospectively from 1st January
      until 31st August 2011. Information was collected on demographics, ethnicity,
      cause and severity of injury, injury location (in or outside the home), other
      injuries and mode of arrival. Deprivation data were obtained by cross-referencing
      postcodes with English Indices of Multiple Deprivation (IMD 2010). For
      comparison, the hospital audit department provided figures for coded head
      injuries during the same period. RESULTS: During the 8 month period, hand
      searching identified 1747 children with minor HI, aged between 0 and 16 years. Of
      these 99% had minimal HI (GCS 15 or 'alert'). In the same period, hospital-coded
      minor HIs numbered only 1081. HIs formed 9% of all CED attendances. Thirteen
      children returned to the CED with worrying symptoms after discharge home.
      Approximately 3.4% of the local paediatric population attend the CED with HI per
      year (3419/100,000 population). Falls accounted for 62% of HIs overall, rising to
      77% in children aged 0-5. Most in-home head injuries (81%) were the result of
      falls (p<0.0001). Significantly more injuries took place inside the home for 0-5
      year olds (58%) than for older children (20%) (p<0.0001). Children living in the
      most deprived areas were more likely to attend the CED with HI (RR: 1.19; CI:
      1.06-1.35, p=0.004), and arrive using emergency services (OR: 1.77; CI: 1.30
      2.40, p<0.001). There were no significant differences between the deprived and
      non-deprived groups for location or cause of injury. CONCLUSIONS: Young children
      are particularly at risk of HI and parents should be offered information on
      injury prevention. More children from deprived areas attended with HI and these
      families may benefit most from targeted interventions.

PMID- 23958555
TI  - A simple template-free 'sputtering deposition and selective etching' process for
      nanoporous thin films and its application to dye-sensitized solar cells.
AB  - A facile and straightforward method is suggested to synthesize nanoporous-TiO2
      thin films for dye-sensitized solar cells (DSSCs). Silver/TiO2 co-sputtering led
      to the formation of nanocomposite films which consisted of silver nanoclusters
      with surrounding TiO2 matrices, and metal particles were subsequently etched by
      just immersing in nitric acid. Nanoporous-TiO2 DSSCs fabricated by this simple
      and effective process showed power-conversion efficiencies of up to 3.4% at a
      thickness of only 1.8 MUm, which is much superior to that of conventional
      nanoparticulate-TiO2 DSSCs with similar thickness.

PMID- 23958556
TI  - A trial of the utilization of stable isotope analysis for the estimation of the
      geographic origins of unidentified cadavers.
AB  - The number of unidentified cadavers is increasing worldwide and the effective
      methods which reveal their geographic origin are not well known. In this study,
      we analyzed the urine stable isotope ratio of hydrogen and oxygen collected from
      three locations: Chiba (Japan), Fuzhou (China), and Denpasar (Indonesia) from
      healthy volunteers. In addition, analysis of the effect of drinking bottled water
      on stable isotope ratios found in urine, and the comparison of the stable isotope
      ratios of urine and saliva, were conducted. Statistically significant differences
      in delta(2)H and delta(18)O values from the three locations were found. In this
      pilot study, urine delta(18)O values became increasingly similar to those of
      bottled drinking water during an eight-day period of drinking only bottled water.
      In a separate pilot study significant differences in delta(18)O, delta(13)C, and
      delta(15)N values from urine and saliva were found, but not in delta(2)H values.
      In all three studies, although the number of samples was limited, the results
      suggest that with further research, stable isotope analysis from urine samples
      might be used to identify the origins of unidentified corpses, assist in
      determining the length of time an individual has been in a given area and
      distinguish between body fluids. 

PMID- 23958558
TI  - Should we lower lipids in nonalcoholic fatty liver disease?

PMID- 23958557
TI  - Keratin 19: a key role player in the invasion of human hepatocellular carcinomas.
AB  - OBJECTIVE: Keratin (K)19, a biliary/hepatic progenitor cell (HPC) marker, is
      expressed in a subset of hepatocellular carcinomas (HCC) with poor prognosis. The
      underlying mechanisms driving this phenotype of K19-positive HCC remain elusive.
      DESIGN: Clinicopathological value of K19 was compared with EpCAM, and alpha
      fetoprotein, in a Caucasian cohort of 242 consecutive patients (167 surgical
      specimens, 75 needle biopsies) with different underlying aetiologies. Using
      microarrays and microRNA profiling the molecular phenotype of K19-positive HCCs
      was identified. Clinical primary HCC samples were submitted to in vitro invasion
      assays and to side population analysis. HCC cell lines were transfected with
      synthetic siRNAs against KRT19 and submitted to invasion and cytotoxicity assays.
      RESULTS: In the cohort of surgical specimens, K19 expression showed the strongest
      correlation with increased tumour size (p<0.01), decreased tumour differentiation
      (p<0.001), metastasis (p<0.05) and microvascular invasion (p<0.001). The
      prognostic value of K19 was also confirmed in a set of 75 needle biopsies.
      Profiling showed that K19-positive HCCs highly express invasion
      related/metastasis-related markers (eg, VASP, TACSTD2, LAMB1, LAMC2, PDGFRA),
      biliary/HPC markers (eg, CD133, GSTP1, NOTCH2, JAG1) and members of the miRNA
      family 200 (eg, miR-141, miR-200c). In vitro, primary human K19-positive tumour
      cells showed increased invasiveness, and reside in the chemoresistant side
      population. Functionally, K19/KRT19 knockdown results in reduced invasion, loss
      of invadopodia formation and decreased resistance to doxorubicin, 5-fluorouracil
      and sorafenib. CONCLUSIONS: Giving the distinct invasive properties, the
      different molecular profile and the poor prognostic outcome, K19-positive HCCs
      should be considered as a seperate entity of HCCs.

PMID- 23958559
TI  - Biliary web: diagnosis with high-definition videocholangioscopy.

PMID- 23958560
TI  - Isolated metastasis of hepatocellular carcinoma in the right ventricle.

PMID- 23958561
TI  - Validation of the determinant-based classification and revision of the Atlanta
      classification systems for acute pancreatitis.
AB  - BACKGROUND & AIMS: Two new classification systems for the severity of acute
      pancreatitis (AP) have been proposed, the determinant-based classification (DBC)
      and a revision of the Atlanta classification (RAC). Our aim was to validate and
      compare these classification systems. METHODS: We analyzed data from adult
      patients with AP (543 episodes of AP in 459 patients) who were admitted to
      Hospital General Universitario de Alicante from December 2007 to February 2013.
      Imaging results were reviewed, and the classification systems were validated and
      compared in terms of outcomes. RESULTS: Pancreatic necrosis was present in 66 of
      the patients (12%), peripancreatic necrosis in 109 (20%), walled-off necrosis in
      61 (11%), acute peripancreatic fluid collections in 98 (18%), and pseudocysts in
      19 (4%). Transient and persistent organ failures were present in 31 patients (6%)
      and 21 patients (4%), respectively. Sixteen patients (3%) died. On the basis of
      the DBC, 386 (71%), 131 (24%), 23 (4%), and 3 (0.6%) patients were determined to
      have mild, moderate, severe, or critical AP, respectively. On the basis of the
      RAC, 363 patients (67%), 160 patients (30%), and 20 patients (4%) were determined
      to have mild, moderately severe, or severe AP, respectively. The different
      categories of severity for each classification system were associated with
      statistically significant and clinically relevant differences in length of
      hospital stay, need for admission to the intensive care unit, nutritional
      support, invasive treatment, and in-hospital mortality. In comparing similar
      categories between the classification systems, no significant differences were
      found. CONCLUSION: The DBC and the RAC accurately classify the severity of AP in
      subgroups of patients.

PMID- 23958562
TI  - Adaptive responses to glucose restriction enhance cell survival, antioxidant
      capability, and autophagy of the protozoan parasite Trichomonas vaginalis.
AB  - BACKGROUND: To establish an infection in the vagina, Trichomonas vaginalis must
      adapt to various environmental cues for survival and further replication.
      Nutrient competition by lactobacilli, the major normal vaginal flora, is one of
      the mechanisms to limit the growth of other microorganisms. Additionally,
      lactobacilli produce H2O2 that can reduce the genital infections caused by other
      pathogens. Thus, the ability to overcome the metabolic stresses, such as glucose
      restriction (GR), as well as the oxidative stresses, is critical for T. vaginalis
      to establish an infection. METHODS: To gain insights into the molecular
      mechanisms of adaptation to GR, we utilized next-generation RNA sequencing (RNA
      seq) to quantify the gene expression changes upon GR. Autophagy, a cytoprotective
      response to starvation, was monitored by using autophagy-specific staining,
      autophagy inhibition assay, and co-localization of autophagosomes with lysosomes.
      RESULTS: We demonstrated that GR promotes the survival of T. vaginalis. Besides,
      GR-cultivated cells exhibit higher H2O2 resistance. Our RNA-seq data revealed
      that genes involved in general energy metabolism were downregulated, whereas
      genes encoding glutamate metabolism-related aminotransferases were strikingly
      upregulated under GR. Furthermore, autophagy was first identified and
      characterized in T. vaginalis under GR. CONCLUSIONS: These data suggest that GR
      induces a metabolic reprogramming, enhancing antioxidant ability and autophagy
      for cellular homeostasis to maintain survival. GENERAL SIGNIFICANCE: Our work not
      only led to significant advances in understanding the transcriptional changes in
      response to GR but also provided possible strategies elicited by GR for T.
      vaginalis to adapt to the vaginal microenvironment.

PMID- 23958563
TI  - Supernumerary proteins of mitochondrial ribosomes.
AB  - BACKGROUND: Messenger RNAs encoded by mitochondrial genomes are translated on
      mitochondrial ribosomes that have unique structure and protein composition
      compared to prokaryotic and cytoplasmic ribosomes. Mitochondrial ribosomes are a
      patchwork of core proteins that share homology with prokaryotic ribosomal
      proteins and new, supernumerary proteins that can be unique to different
      organisms. In mammals, there are specific supernumerary ribosomal proteins that
      are not present in other eukaryotes. SCOPE OF REVIEW: Here we discuss the roles
      of supernumerary proteins in the regulation of mitochondrial gene expression and
      compare them among different eukaryotic systems. Furthermore, we consider if
      differences in the structure and organization of mitochondrial genomes may have
      contributed to the acquisition of mitochondrial ribosomal proteins with new
      functions. MAJOR CONCLUSIONS: The distinct and diverse compositions of
      mitochondrial ribosomes illustrate the high evolutionary divergence found between
      mitochondrial genetic systems. GENERAL SIGNIFICANCE: Elucidating the role of the
      organism-specific supernumerary proteins may provide a window into the regulation
      of mitochondrial gene expression through evolution in response to distinct
      evolutionary paths taken by mitochondria in different organisms. This article is
      part of a Special Issue entitled Frontiers of Mitochondrial Research.

PMID- 23958564
TI  - Transforming growth factor-beta signaling in schistosomiasis-induced pulmonary
      hypertension: a perspective for antifibrotic drugs?

PMID- 23958566
TI  - Inverse problems and material identification in tissue biomechanics.

PMID- 23958565
TI  - Transforming growth factor-beta signaling promotes pulmonary hypertension caused
      by Schistosoma mansoni.
AB  - BACKGROUND: The pathogenic mechanisms underlying pulmonary arterial hypertension
      resulting from schistosomiasis, one of the most common causes of pulmonary
      hypertension worldwide, remain unknown. We hypothesized that transforming growth
      factor-beta (TGF-beta) signaling as a consequence of Th2 inflammation is critical
      for the pathogenesis of this disease. METHODS AND RESULTS: Mice sensitized and
      subsequently challenged with Schistosoma mansoni eggs developed pulmonary
      hypertension associated with an increase in right ventricular systolic pressure,
      thickening of the pulmonary artery media, and right ventricular hypertrophy. Rho
      kinase-dependent vasoconstriction accounted for ~60% of the increase in right
      ventricular systolic pressure. The pulmonary vascular remodeling and pulmonary
      hypertension were dependent on increased TGF-beta signaling, as pharmacological
      blockade of the TGF-beta ligand and receptor, and mice lacking Smad3 were
      significantly protected from Schistosoma-induced pulmonary hypertension. Blockade
      of TGF-beta signaling also led to a decrease in interleukin-4 and interleukin-13
      concentrations, which drive the Th2 responses characteristic of schistosomiasis
      lung pathology. Lungs of patients with schistosomiasis-associated pulmonary
      arterial hypertension have evidence of TGF-beta signaling in their remodeled
      pulmonary arteries. CONCLUSION: Experimental S mansoni-induced pulmonary vascular
      disease relies on canonical TGF-beta signaling.

PMID- 23958567
TI  - Significance of observational data on type 2 diabetes management in North Africa.

PMID- 23958568
TI  - Safety and effectiveness of insulin analogues in type 2 diabetic patients from
      Algeria: a sub-analysis of the A1chieve study.
AB  - AIM: To determine the safety and effectiveness of insulin analogues in type 2
      diabetes (T2D) patients in the Algerian cohort of the A1chieve study and to
      examine the status of T2D management across different regions in Algeria.
      METHODS: Patients starting therapy with biphasic insulin aspart 30, insulin
      detemir, insulin aspart (IAsp) or IAsp + basal insulin at their physicians'
      decision were included. The primary outcome was the incidence of serious adverse
      drug reactions (SADRs), including major hypoglycaemia. Secondary outcomes
      included changes from baseline to Week 24 in hypoglycaemia, glycated haemoglobin
      A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG),
      weight and quality of life (QoL, evaluated using the EQ-5D questionnaire).
      RESULTS: Overall, 1494 patients (mean +/- SD age: 60.1 +/- 10.3 years; body mass
      index: 28.1 +/- 4.9 kg/m(2); HbA1c: 9.2 +/- 1.8%) were enrolled. Poor baseline
      glucose control was revealed across the different Algerian regions with mean
      HbA1c varying from 8.9% to 9.6%. Two SADRs were reported during the study. The
      proportion of patients reporting major hypoglycaemic events decreased from 1.1%
      at baseline to 0.2% at Week 24 (p = 0.0017). Significant improvements in mean
      HbA1c (-1.3 +/- 2.0%), FPG (-38.8 +/- 79.9 mg/dL) and post-breakfast PPPG (-51.4
      +/- 97.1 mg/dL) were observed in the entire cohort (all p < 0.001). The mean body
      weight increased by 0.9 +/- 3.8 kg, while QoL increased by 9.2 +/- 16.7 points
      after 24 weeks. CONCLUSIONS: Insulin analogue therapy was well-tolerated and
      significantly improved blood glucose control over 24 weeks in the Algerian
      cohort.

PMID- 23958569
TI  - Safety and effectiveness of insulin analogues in Moroccan patients with type 2
      diabetes: a sub-analysis of the A1chieve study.
AB  - AIM: To determine the safety and effectiveness of insulin analogues in the
      Moroccan cohort of the prospective, multinational, non-interventional, 24-week
      A1chieve study. METHODS: Moroccan patients with type 2 diabetes (T2D) starting
      biphasic insulin aspart 30, insulin detemir, and insulin aspart alone or in
      combination were included. The primary outcome was the evaluation of serious
      adverse drug reactions including major hypoglycaemic events. Secondary outcomes
      were changes in hypoglycaemic events, glycaemic parameters (HbA1c, fasting plasma
      glucose [FPG], postprandial plasma glucose [PPPG]), systolic blood pressure
      (SBP), body weight and lipid profile. Quality of life (QoL) was evaluated using
      the EQ-5D questionnaire. RESULTS: In this analysis, 1641 patients (923 insulin
      naive, 718 insulin-experienced) having a mean age 57.1 years, mean BMI 26.8
      kg/m(2) and mean diabetes duration 10.3 years, were included. Baseline HbA1c in
      the entire cohort was poor (9.7%, 83 mmol/mol). Insulin analogues statistically
      significantly improved glucose control (HbA1c, FPG and PPPG, p < 0.001) at Week
      24. The rate of hypoglycaemia decreased from 9.31 to 4.71 events/patient-year
      (change in proportion of patients affected, p = 0.0002). A statistically
      significant improvement in lipid parameters (except HDL cholesterol) was observed
      while body weight changed minimally. Additionally, QoL was positively impacted
      (mean change in visual analogue scores from EQ-5D was 15.8 points, p < 0.001).
      CONCLUSIONS: Insulin analogue therapy resulted in improved glycaemic control and
      a significant overall decrease in hypoglycaemia in Moroccan T2D patients.

PMID- 23958570
TI  - Initiating or switching to biphasic insulin aspart 30 in type 2 diabetes patients
      from Algeria: a sub-analysis of the A1chieve study.
AB  - AIM: To determine the safety and effectiveness of biphasic insulin aspart 30
      (BIAsp 30) in Algerian patients with type 2 diabetes initiating insulin or
      switching from prior insulin therapy. METHODS: Insulin-naive and insulin
      experienced patients, including prior basal insulin users, starting BIAsp 30 were
      evaluated in this sub-analysis of the 24-week, open-label, non-interventional
      A1chieve study. Clinical safety and effectiveness was evaluated as a part of
      routine clinical care. RESULTS: A total of 134 insulin-naive patients initiating
      BIAsp 30 at a mean dose of 0.44 +/- 0.23 U/kg and 283 insulin-experienced
      patients, including 129 prior basal insulin users, switching from a mean pre
      study insulin dose of 0.51 +/- 0.23 U/kg to BIAsp 30 (0.54 +/- 0.20 U/kg) were
      evaluated. At Week 24, the average BIAsp 30 dose was 0.60 +/- 0.25 U/kg and 0.66
      +/- 0.24 U/kg in insulin-naive and insulin-experienced patients, respectively. No
      serious adverse drug reactions were reported. From baseline to Week 24, the
      proportion of patients experiencing overall hypoglycaemia increased in the
      insulin-naive group (p = 0.0067) and no significant changes were reported in the
      insulin-experienced group including prior basal insulin users. Glucose control
      improved significantly in the insulin-experienced group (p < 0.001) and appeared
      to improve in the insulin-naive patients and prior basal insulin users as well.
      Body weight increased significantly in all patients (p < 0.001). Quality of life
      was positively impacted after 24 weeks of BIAsp 30 therapy. CONCLUSION:
      Initiating or switching to BIAsp 30 therapy in this Algerian cohort was well
      tolerated and significantly improved glucose control.

PMID- 23958571
TI  - Exploring insulin analogue safety and effectiveness in a Maghrebian cohort with
      type 2 diabetes: results from the A1chieve study.
AB  - AIM: To evaluate the safety and effectiveness of insulin analogues in patients
      with type 2 diabetes (T2D) from Morocco, Algeria and Tunisia that formed the
      Maghrebian cohort of the 24-week, non-interventional A1chieve study. METHODS:
      Patients starting biphasic insulin aspart, insulin detemir and insulin aspart,
      alone or in combination, were included. The primary outcome was the incidence of
      serious adverse drug reactions (SADRs), including major hypoglycaemic events.
      Secondary outcomes included hypoglycaemia, glycated haemoglobin A1c (HbA1c),
      fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), systolic blood
      pressure (SBP), body weight and lipids. Quality of life (QoL) was evaluated using
      the EQ-5D questionnaire. RESULTS: Overall, 3720 patients with a mean age of 58.6
      years, body mass index of 27.7 kg/m(2) and diabetes duration of 11.5 years were
      enrolled. Pre-study, insulin-experienced patients had a mean +/- SD dose of 0.54
      +/- 0.27 U/kg. In the entire cohort, the mean dose was 0.42 +/- 0.27 U/kg at
      baseline, titrated to 0.55 +/- 0.30 U/kg by Week 24. Twenty-six SADRs were
      reported during the study. There was a significant decrease in the proportion of
      patients reporting overall hypoglycaemia from baseline to Week 24 (18.3% to
      13.8%, p < 0.0001). The mean HbA1c improved significantly from 9.5 +/- 1.8% to
      7.9 +/- 1.4% (p < 0.001). The mean FPG, PPPG, SBP, total cholesterol and QoL also
      improved significantly (all p < 0.001), while the mean body weight increased by
      0.9 +/- 3.9 kg (p < 0.001). CONCLUSION: Insulin analogue therapy was well
      tolerated and was associated with improved glycaemic control.

PMID- 23958572
TI  - Criteria influencing the choice of starting insulin regimen in patients with type
      2 diabetes in routine clinical practice: baseline data from the Algerian cohort
      of the A1chieve study.
AB  - AIM: To examine the criteria that may influence physicians' choice of starting
      insulin in type 2 diabetes patients in routine practice in Algeria as a sub
      analysis of the A1chieve study. METHODS: A1chieve was a 24-week international,
      prospective, non-interventional study conducted to evaluate the safety and
      effectiveness of biphasic insulin aspart 30 (BIAsp 30), insulin detemir (IDet),
      or insulin aspart alone or in combination, in real-life clinical settings. We
      report an analysis of baseline data from insulin-naive patients initiating basal
      or premix insulin from the Algeria cohort (n = 1494). Demographic and
      anthropometric data, blood glucose control at inclusion, microvascular
      complications, and pre-study therapy was compared between the two groups.
      RESULTS: A total of 772 insulin-naive patients initiating therapy with IDet or
      BIAsp 30 were included in this analysis: IDet: 638 (83%), BIAsp 30: 134 (17%).
      Most IDet-group patients initiated once-daily therapy (n = 636; 99.7%);
      conversely, most BIAsp 30-group patients started twice-daily therapy (n = 104;
      77.6%). Baseline factors influencing regimen choice were microvascular
      complications (odds ratio [95% CI], yes/no: 0.73 [0.55, 0.98]; p = 0.034) and
      HbA1c at baseline (%, odds ratio [95% CI] 0.82 [0.72, 0.94]; p = 0.004).
      CONCLUSIONS: In routine practice, physicians in Algeria are more likely to
      prescribe basal insulin at initiation of insulin therapy in type 2 diabetes. The
      prescription of a premix insulin therapy correlated with poor glycaemic control
      and the incidence of microvascular complications.

PMID- 23958574
TI  - Cord blood unit bankability can be predicted by prenatal sonographic parameters.
AB  - OBJECTIVE: To identify possible sonographic prenatal parameters and postnatal
      parameters in order to obtain more bankable cord blood units (CBUs) containing a
      high number of primitive progenitor cells, allowing CBUs to be used as a source
      of haematopoietic progenitors for clinical transplantation. STUDY DESIGN:
      Prospective study undertaken in the Department of Gynaecology, Obstetrics and
      Reproductive Science, Second University of Naples, Italy. In total, 219 unrelated
      CBU donors were enrolled. Ultrasound parameters (biparietal diameter, head
      circumference, abdominal circumference, femur length, estimation of fetal weight,
      umbilical artery pulsatility index), collected at hospital admission, together
      with birth weight and placental weight, were correlated with bankable CBU
      parameters (CBU volume, total nucleated cell count, CD34+ cell count). RESULTS:
      Femur length and abdominal circumference correlated positively with bankable
      CBUs. Receiver operating curve analysis showed that these parameters can identify
      bankable CBUs. CONCLUSIONS: This is the first prospective study to show the
      relationship between ultrasonographic fetal parameters at term and the
      possibility of obtaining high-quality CBUs. As such, cord blood banking could be
      improved worldwide by performing low-cost ultrasonographic scans.

PMID- 23958573
TI  - Endostatin levels and the risk of subsequent preeclampsia.
AB  - OBJECTIVE: To evaluate endostatin, an anti-angiogenic factor, in relation to the
      risk of preeclampsia (PE). STUDY DESIGN: In this case control study, serum
      samples were collected at 11-17 weeks and 18-26 weeks' gestation. Endostatin
      levels were expressed as adjusted multiples of the median (MoM). Logistic
      regression was used to calculate adjusted odds ratios (aORs) for the prediction
      of PE. RESULTS: A total of 77 women with PE and 150 controls were studied.
      Endostatin levels were significantly higher in women with PE compared to controls
      in both the first and the second trimester. At a cut-off level of 75th percentile
      of endostatin MoMs, the aORs for PE were 1.33 (95% confidence interval [CI], 0.68
      2.58) at 11-17 weeks and 1.77 (95% CI, 0.94-3.34) at 18-26 weeks, after
      adjustment for ethnicity and chronic hypertension. The aORs for early-onset PE
      were 3.51 (95% CI, 1.18-10.43) at 11-17 weeks and 2.17 (95% CI, 0.67-7.06) at 18
      26 weeks. CONCLUSIONS: Higher endostatin levels are associated with an increased
      risk of early onset PE. Endostatin alone, however, has a poor predictive value
      for clinical usefulness.

PMID- 23958575
TI  - Topical ibuprofen inhibits blushing during embarrassment and facial flushing
      during aerobic exercise in people with a fear of blushing.
AB  - The flush that develops during whole-body heat stress depends partly on
      prostaglandins production in the skin. Variations in the strength of this local
      mechanism may contribute to individual differences in susceptibility to blushing
      and associated anxiety. To investigate this in the present study, the anti
      inflammatory agent ibuprofen (which blocks prostaglandins formation) was applied
      topically to a small area of the cheek in 16 participants with a fear of blushing
      and in another 14 without this fear. Changes in skin blood flow were monitored at
      the ibuprofen-treated site and at a mirror image control site while participants
      sang (to induce embarrassment and blushing) and during aerobic exercise (to
      induce flushing). The topical ibuprofen treatment inhibited increases in cheek
      blood flow in both groups during both of these tasks. However, increases in cheek
      blood flow were greater in participants with high than low fear of blushing
      immediately after exercise. These findings suggest that prostaglandins contribute
      to dilatation of facial blood vessels both during emotional arousal
      (embarrassment) and aerobic exercise. Furthermore, fear of blushing may be
      associated with mechanisms that delay the resumption of normal vascular tone
      after a period of vasodilatation. Whether topical ibuprofen gel is suitable for
      intermittent or long-term use as an aid for blushing control requires further
      investigation. 

PMID- 23958576
TI  - Ultrastructural immunolocalization of alpha-keratins and associated beta-proteins
      (beta-keratins) suggests a new interpretation on the process of hard and soft
      cornification in turtle epidermis.
AB  - The epidermis of soft-shelled and hard-shelled turtles has been compared to
      determine the origin of the different cornification. Immunolocalization of acidic
      alpha-keratin (AK2) of 45-50 kDa in tonofilaments of the epidermis in Apalone
      spinifera and absence in the corneous layer where desquamating corneocytes are
      present supports the biochemical data. Corneocytes shows a weak to absent
      immunolabeling for beta-proteins (formerly beta-keratins) of 14-16 kDa while
      sparse immunolabeled corneous granules are seen in the pre-corneous layer. In the
      hard-shelled turtle Pseudemys nelsonii differentiating corneocytes contain small
      level of acidic alpha-keratin while beta-proteins of 10-17 kDa form dense
      aggregates of corneous material among tonofilaments. Corneocytes do not
      desquamate but remain tightly connected determining an increase in thickness of
      the corneous layer that becomes mechanically stiff and resistant. Since both
      species possess beta-proteins in shelled and non-shelled areas of the epidermis
      the difference in hardness of the corneous layer is not due to the alternation
      between beta-keratin versus alpha-keratin. Mechanical resilience of the corneous
      layer derives from the accumulation of alpha-keratins, beta- and likely of other
      proteins in corneocytes of the shell in hard-shelled turtles. In the softer
      epidermis of hard-shelled turtles and in the soft-shelled turtle a more rapid and
      continuous turnover of corneocytes is present and no accumulation of beta
      proteins and corneocytes takes place. It is hypothesized that the dermis derived
      from the carapacial ridge during development remains localized underneath the
      shell epidermis in hard-shelled turtles and influences the formation of the hard
      corneous epidermis.

PMID- 23958578
TI  - Pharmacological alterations that could underlie radiation-induced changes in
      associative memory and anxiety.
AB  - It is widely known that ionizing radiation is a physical agent broadly used to
      kill tumor cells during human cancer therapy. Unfortunately, adjacent normal
      tissues can concurrently undergo undesirable cell injury. Previous data of our
      laboratory demonstrated that exposure of developing rats to ionizing radiations
      induced a variety of behavioral differences respect to controls, including
      changes in associative memory and in anxiety state. However, there is a lack of
      data concerning modifications in different related pharmacological
      intermediaries. Therefore, the aim of the present study was to investigate
      whether the behavioral differences observed in young animals irradiated at birth
      might be underlain by early changes in PKCbeta1 levels which, in turn, could lead
      to changes in hippocampal GABAergic neurotransmission. Male Wistar rats were
      irradiated with 5Gy of X rays between 24 and 48 h after birth. Different
      pharmacological markers related to the affected behavioral tasks were assessed in
      control and irradiated hippocampus at 15 and 30 days, namely GABAA receptor,
      GAD65-67, ROS and PKCbeta1. Results showed that all measured parameters were
      increased in the hippocampus of 30-days-old irradiated animals. In contrast, in
      the hippocampus of 15-days-old irradiated animals only the levels of PKCbeta1
      were decreased. These data suggest that PKCbeta1 might constitute a primary
      target for neonatal radiation damage on the hippocampus. Therefore, it could be
      hypothesized that an initial decrease in the levels of this protein can trigger a
      subsequent compensatory increase that, in turn, could be responsible for the
      plethora of biochemical changes that might underlie the previously observed
      behavioral alterations.

PMID- 23958579
TI  - Spinal D-amino acid oxidase contributes to mechanical pain hypersensitivity
      induced by sleep deprivation in the rat.
AB  - We studied the hypothesis that spinal d-amino acid oxidase (DAAO) that is
      expressed in astrocytes and that has been reported to promote tonic pain in
      various pathophysiological conditions plays a role in 'physiological' pain
      hypersensitivity induced by rapid eye movement sleep deprivation (REMSD). The
      experiments were performed in healthy rats with a chronic intrathecal (i.t.)
      catheter. Pain behavior was assessed by determining limb withdrawal response to
      repetitive stimulation of the hind paw with a calibrated series of monofilaments.
      REMSD of 48 h duration produced a significant mechanical hypersensitivity. At 48
      h of REMSD, the animals were treated i.t. with a DAAO inhibitor or vehicle. Three
      structurally different DAAO inhibitors were tested in this study: 6
      chlorobenzo[d]isoxazol-3-ol (CBIO), sodium benzoate, and 5-methylpyrazole-3
      carboxylic acid (AS-057278). CBIO (1-3 MUg), sodium benzoate (30-100 MUg) and AS
      057278 (3-10 MUg) produced dose-related antihypersensitivity effects in sleep
      deprived animals. In control animals (with no sleep deprivation), the currently
      used doses of DAAO inhibitors failed to produce significant changes in
      mechanically evoked pain behavior. The results indicate that among spinal pain
      facilitatory mechanisms that contribute to the sleep deprivation-induced
      mechanical pain hypersensitivity is DAAO, presumably due to production of
      reactive oxygen species, such as hydrogen peroxide, an endogenous agonist of the
      pronociceptive TRPA1 ion channel.

PMID- 23958580
TI  - 96-hour methamphetamine self-administration in male and female rats: a novel
      model of human methamphetamine addiction.
AB  - Methamphetamine (MA) is a highly addictive psychostimulant drug of abuse for
      which no FDA-approved treatment exists. While high on MA, both male and female MA
      users report engaging in risky behaviors and are more likely to be involved in
      violent criminal activities and to engage in domestic and sexual violence. A
      unique aspect of MA is that it is typically used in binges. However, there is no
      animal model of MA self-administration that appears to represent a human MA self
      administration binge. We recently developed a 96-hour MA self-administration
      paradigm in rats that more closely resembles how human MA users take the drug.
      Male and female rats were trained to self-administer MA for 96 consecutive hours
      for 5 weeks. Responding by female and male rats tended to escalate to binge-like
      behavior, as the animals responded continuously during their normal periods of
      activity as well as during their inactive periods for up to 72 h, followed by a
      crash of 6 or more hours. Thus, this 96-hour model of MA self-administration is a
      novel way to study MA addition in rats that may contribute to the development of
      improved treatments for recovering human MA users.

PMID- 23958581
TI  - DNA probe modified with 3-iron bis(dicarbollide) for electrochemical
      determination of DNA sequence of Avian Influenza Virus H5N1.
AB  - In this work, we report on oligonucleotide probes bearing metallacarborane [3
      iron bis(dicarbollide)] redox label, deposited on gold electrode for
      electrochemical determination of DNA sequence derived from Avian Influenza Virus
      (AIV), type H5N1. The oligonucleotide probes containing 5'-terminal NH2 group
      were covalently attached to the electrode, via NHS/EDC coupling to 3
      mercaptopropionic acid SAM, previously deposited on the surface of gold. The
      changes in redox activity of Fe(III) centre of the metallacarborane complex
      before and after hybridization process was used as analytical signal. The signals
      generated upon hybridization with targets such as complementary or non
      complementary 20-mer ssDNA or various PCR products consisting of 180-190 bp
      (dsDNA) were recorded by Osteryoung square-wave voltammetry (OSWV). The developed
      system was very sensitive towards targets containing sequence complementary to
      the probe with the detection limit estimated as 0.03 fM (S/N=3.0) and 0.08 fM
      (S/N=3.0) for 20-mer ssDNA and for dsDNA (PCR product), respectively. The non
      complementary targets generated very weak responses. Furthermore, the proposed
      genosensor was suitable for discrimination of PCR products with different
      location of the complementarity region.

PMID- 23958582
TI  - Efficient genome editing in plants using a CRISPR/Cas system.

PMID- 23958583
TI  - The years of the monkey.
AB  - The fact that mammals are diploid sets a barrier to rapidly understand the
      function of non-coding and coding genes in the genome. Recently, Yang et al.
      reported successful derivation of monkey haploid embryonic stem cells from
      parthenotes, which provide an effective platform for studying mammalian gene
      function and enable reverse genetic screening of genes for recessive phenotypes
      in monkeys. 

PMID- 23958585
TI  - Neural correlates of sexual arousal in heterosexual and homosexual women and men.
AB  - Most men have a category-specific pattern of genital and subjective sexual
      arousal, responding much more strongly to erotic stimuli depicting their
      preferred sex than to erotic stimuli depicting their nonpreferred sex. In
      contrast, women tend to have a less specific arousal pattern. To better
      understand this sex difference, we used neuroimaging to explore its neural
      correlates. Heterosexual and homosexual women viewed erotic photographs of either
      men or women. Evoked neural activity was monitored via fMRI and compared with
      responses to the same stimuli in heterosexual and homosexual men. Overall, a
      network of limbic (as well as the anterior cingulate) and visual processing
      regions showed significantly less category-specific activity in women than men.
      This was primarily driven by weaker overall activations to preferred-sex stimuli
      in women, though there was also some evidence of stronger limbic activations to
      nonpreferred-sex stimuli in women. Primary results were similar for heterosexual
      and homosexual participants. Women did show some evidence of category-specific
      responses in the visual processing regions, although even in these regions they
      exhibited less differential activity than men. In the anterior cingulate, a
      region with high concentrations of sex-hormone receptors, subjective and neural
      category specificity measures correlated positively for women but negatively for
      men, suggesting a possible sex difference in the role of the anterior cingulate.
      Overall, results suggest that men tend to show more differentiated neural
      responses than do women to erotic photographs of one sex compared to the other
      sex, though women may not be entirely indifferent to which sex is depicted. 

PMID- 23958584
TI  - Usage of a generic web-based self-management intervention for breast cancer
      survivors: substudy analysis of the BREATH trial.
AB  - BACKGROUND: Generic fully automated Web-based self-management interventions are
      upcoming, for example, for the growing number of breast cancer survivors. It is
      hypothesized that the use of these interventions is more individualized and that
      users apply a large amount of self-tailoring. However, technical usage
      evaluations of these types of interventions are scarce and practical guidelines
      are lacking. OBJECTIVE: To gain insight into meaningful usage parameters to
      evaluate the use of generic fully automated Web-based interventions by assessing
      how breast cancer survivors use a generic self-management website. Final aim is
      to propose practical recommendations for researchers and information and
      communication technology (ICT) professionals who aim to design and evaluate the
      use of similar Web-based interventions. METHODS: The BREAst cancer ehealTH
      (BREATH) intervention is a generic unguided fully automated website with stepwise
      weekly access and a fixed 4-month structure containing 104 intervention
      ingredients (ie, texts, tasks, tests, videos). By monitoring https-server
      requests, technical usage statistics were recorded for the intervention group of
      the randomized controlled trial. Observed usage was analyzed by measures of
      frequency, duration, and activity. Intervention adherence was defined as
      continuous usage, or the proportion of participants who started using the
      intervention and continued to log in during all four phases. By comparing
      observed to minimal intended usage (frequency and activity), different user
      groups were defined. RESULTS: Usage statistics for 4 months were collected from
      70 breast cancer survivors (mean age 50.9 years). Frequency of logins/person
      ranged from 0 to 45, total duration/person from 0 to 2324 minutes (38.7 hours),
      and activity from opening none to all intervention ingredients. 31 participants
      continued logging in to all four phases resulting in an intervention adherence
      rate of 44.3% (95% CI 33.2-55.9). Nine nonusers (13%), 30 low users (43%), and 31
      high users (44%) were defined. Low and high users differed significantly on
      frequency (P<.001), total duration (P<.001), session duration (P=.009), and
      activity (P<.001). High users logged in an average of 21 times, had a mean
      session duration of 33 minutes, and opened on average 91% of all ingredients.
      Signing the self-help contract (P<.001), reporting usefulness of ingredients
      (P=.003), overall satisfaction (P=.028), and user friendliness evaluation
      (P=.003) were higher in high users. User groups did not differ on age, education,
      and baseline distress. CONCLUSIONS: By reporting the usage of a self-management
      website for breast cancer survivors, the present study gained first insight into
      the design of usage evaluations of generic fully automated Web-based
      interventions. It is recommended to (1) incorporate usage statistics that reflect
      the amount of self-tailoring applied by users, (2) combine technical usage
      statistics with self-reported usefulness, and (3) use qualitative measures. Also,
      (4) a pilot usage evaluation should be a fixed step in the development process of
      novel Web-based interventions, and (5) it is essential for researchers to gain
      insight into the rationale of recorded and nonrecorded usage statistics. TRIAL
      REGISTRATION: Netherlands Trial Register (NTR): 2935;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2935 (Archived by
      WebCite at http://www.webcitation.org/6IkX1ADEV).

PMID- 23958586
TI  - Analysis of cesarean delivery at Assiut University Hospital using the Ten Group
      Classification System.
AB  - OBJECTIVE: To evaluate the feasibility of using the Robson Ten Group
      Classification System (TGCS) for cesarean delivery (CD) indications at
      institutional level. METHODS: Prospective clinical audits of women delivering by
      CD at Women's Health Hospital, Assiut, Egypt, were conducted in 2008 and 2011.
      The CD rates overall and in each Robson group were calculated, as was the
      contribution of each group to the overall CD rate. In addition, the CD
      indications in each group were analyzed. RESULTS: The CD rate was 32% (443/1357)
      in 2008 and 38% (626/1628) in 2011. The most common CD indication at both time
      intervals was a previous CD. Multiparas without uterine scar, a single cephalic
      term pregnancy, and spontaneous labor (Robson Group 3) comprised the largest
      group of women undergoing CD, followed by nulliparas with a single cephalic term
      pregnancy and spontaneous labor (Group 1), and multiparas with a scarred uterus
      and a single cephalic term pregnancy (Group 5). Group 5 was the largest
      contributor (30%) to the overall CD rate, followed by Groups 1 and 4 (10% each).
      CONCLUSION: The TGCS can be applied at institutional level. It helps in planning
      strategies for specific subgroups of women to reduce CD rates and improve
      outcomes.

PMID- 23958587
TI  - Water-assisted chemical vapor deposition synthesis of boron nitride nanotubes and
      their photoluminescence property.
AB  - A novel water-assisted chemical vapor deposition (CVD) method for the efficient
      synthesis of boron nitride (BN) nanotubes is demonstrated. The replacement of
      metal oxide by water vapor could continuously generate intermediate boron oxide
      vapor and enhance the production of BN nanotubes. The nanotubes synthesized when
      an appropriate amount of water vapor was introduced had an average diameter of
      about 80 nm and lengths of several hundred MUm. The diameter and yield of
      nanotubes could be controlled by tuning the amount of water vapor. This simple
      water-assisted CVD approach paves a new path to the fabrication of BN nanotubes
      in large quantities.

PMID- 23958588
TI  - Role of genotype G hepatitis B virus mixed infection on the progression of
      hepatic fibrosis in HIV positive patients over 5 years of follow-up.
AB  - BACKGROUND: Due to common routes of transmission, HIV and HBV are frequently
      found as concomitant infections. The dynamic of liver disease in co-infected
      patients is important to understand for appropriate clinical management.
      Conflicting data surround the role played by genotype-G HBV (HBV-G) during the
      course of HIV co-infection. OBJECTIVES: This study aims to assess, using non
      invasive methods, liver disease progression in HIV-HBV genotype-G co-infected
      patients. STUDY DESIGN: Co-infected patients with residual HBV replication
      (n=125) were screened for HBV-G infection by specific real-time PCR. The impact
      of HBV-G on liver fibrosis progression, as assessed by a non invasive biomarker
      (Fibrotest), was evaluated first, by a cross sectional analysis comparing
      fibrosis between HBV-G (n=23) and non-G (n=55) infected patients and second, by a
      longitudinal study performed over a 5 year period. RESULTS: Selected patients
      were mostly male (90%), with homogenous characteristics between the HBV-G and non
      G infected groups, in terms of age, known duration of HIV disease, immune and
      virological status and duration of HIV/HBV treatment. HBV-G infected patients
      were exclusively from Western Europe with homosexual intercourses (83%) as
      principal risk of transmission. Cross sectional analysis revealed comparable
      liver disease severity distribution between HBV-G and non-G infected patients. Co
      infection with other hepatitis viruses and low CD4-nadir, but not HBV-G co
      infection, were associated with a 5-year risk of fibrosis progression.
      CONCLUSIONS: This study suggests that HBV-G infection is not significantly
      associated with a more severe liver disease and does not have a deleterious
      impact on fibrosis progression in efficiently treated HIV-HBV co-infected
      patients.

PMID- 23958589
TI  - Health care for people with dementia in 2030 - results of a multidisciplinary
      scenario process.
AB  - BACKGROUND: Despite extensive research funding in the field of dementia, deficits
      in the quality of dementia care still exist. In order to project different
      alternative futures of health care for people with dementia (PwD) in Germany, we
      have initiated a multidisciplinary scenario process (Sce-Dem). METHODS: For the
      scenario process we used a 6-step approach: (1) identification of relevant areas
      of influences via literature review and internet search, (2) systematic
      collection of relevant influence factors and their future projections via
      literature review, brainstorming and consensus workshops, (3) discussion and
      validation of the identified key factors in a workshop with 52 multidisciplinary,
      experts, to clarify their characteristics and future projections, (4) combining
      the relevant key factors with alternative projections in a so-called consistency
      matrix to estimate the consistency between the selected projections, (5)
      generating consistent combinations of projections using software, and (6) writing
      scenario stories and descriptions based on the most consistent and different
      combinations. RESULTS: As a result of the scenario process, five consistent
      scenarios were developed. Two of these could be described as dark scenarios with
      very poor prospects. A third one has been referred to as "well-meant, but badly
      done". Two scenarios entail mostly positive aspects but one of them has a
      tendency towards, a "health control" state. CONCLUSION: The more positive
      scenarios provide a framework for determining relevant actions in research,
      society, and politics.

PMID- 23958590
TI  - Budget-makers and health care systems.
AB  - Health programs are shaped by the decisions made in budget processes, so how
      budget-makers view health programs is an important part of making health policy.
      Budgeting in any country involves its own policy community, with key players
      including budgeting professionals and political authorities. This article reviews
      the typical pressures on and attitudes of these actors when they address health
      policy choices. The worldview of budget professionals includes attitudes that are
      congenial to particular policy perspectives, such as the desire to select
      packages of programs that maximize population health. The pressures on political
      authorities, however, are very different: most importantly, public demand for
      health care services is stronger than for virtually any other government
      activity. The norms and procedures of budgeting also tend to discourage adoption
      of some of the more enthusiastically promoted health policy reforms. Therefore
      talk about rationalizing systems is not matched by action; and action is better
      explained by the need to minimize blame. The budget-maker's perspective provides
      insight about key controversies in healthcare policy such as decentralization,
      competition, health service systems as opposed to health insurance systems, and
      dedicated vs. general revenue finance. It also explains the frequency of various
      "gaming" behaviors. 

PMID- 23958591
TI  - Tapia's syndrome secondary to laterocervical localization of diffuse large cell
      lymphoma.
AB  - The eponym "Tapia's syndrome" indicates an associated unilateral vocal cord and
      tongue paralysis secondary to a peripheral involvement of the recurrent laryngeal
      branch and the hypoglossal nerve. Although mainly observed as a complication of
      surgery or anaesthesia, it can rarely occur secondary to infectious or neoplastic
      causes. We are presenting a case of a teen-ager with Tapia's syndrome who had
      been seeking medical assistance for episodes of loss of consciousness and was
      diagnosed with a high-grade peripheral B-cell lymphoma, an association not
      previously described. This syndrome should be remembered even outside the
      surgical contest for its highly localising value. 

PMID- 23958592
TI  - Metabolic encephalopathy in beta-ketothiolase deficiency: the first report from
      India.
AB  - Beta-ketothiolase deficiency, or mitochondrial acetoacetyl-CoA thiolase (T2)
      deficiency, is a rare autosomal recessive disorder affecting isoleucine
      catabolism and ketone body metabolism. A patient from South India presented with
      acute ketoacidosis at 11 months of age. During the acute crisis the C5OH (2
      methyl-3-hydroxybutyryl) carnitine and C5:1 (tiglyl) carnitine were elevated and
      large amounts of 2-methyl-3-hydroxybutyrate, tiglylglycine, and 2
      methylacetoacetate were excreted. Brain CT showed bilateral basal ganglia
      lesions. Potassium ion-activated acetoacetyl-CoA thiolase activity was deficient
      in the patient's fibroblasts. The patient is a homozygote for a novel c.578T>G
      (M193R) mutation. This is the first report of T2 deficiency confirmed by enzyme
      and molecular analysis from India.

PMID- 23958593
TI  - RBPJ is disrupted in a case of proximal 4p deletion syndrome with epilepsy.
AB  - Proximal 4p deletion syndrome is characterized clinically by mental retardation,
      minor dysmorphic facial features, and is occasionally complicated with epilepsy.
      More than 20 cases of proximal 4p deletion syndrome have been reported, but the
      causative gene(s) remain elusive. We describe here a 2-year-old female patient
      with a common manifestation of proximal 4p deletion syndrome and infantile
      epileptic encephalopathy possessing a de novo balanced translocation
      t(4;13)(p15.2;q12.13). The patient was diagnosed as infantile spasms at 9 months
      of age. She presented with dysmorphic facial features and global developmental
      delay, compatible with proximal 4p deletion syndrome. Using fluorescence in situ
      hybridization, we determined the translocation breakpoint at 4p15.2 to be within
      RBPJ. RBPJ is a transcription factor in the Notch/RBPJ signaling pathway, playing
      a crucial role in the developing human brain, and particularly telencephalon
      development. Our findings, combined with those of previous studies, strongly
      suggest that RBPJ is causative for proximal 4p deletion syndrome and epilepsy in
      this case.

PMID- 23958594
TI  - Evaluation of FDG-PET and ECD-SPECT in patients with subcortical band
      heterotopia.
AB  - OBJECTIVE: The purpose of this retrospective study was to clarify the cellular
      activities of ectopic neurons in subcortical bands and to evaluate the imaging
      features of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and
      (99m)Tc ethyl cysteinate dimer (ECD) single-photon emission computed tomography
      (SPECT) in a series of patients with subcortical band heterotopia (SBH).
      MATERIALS AND METHODS: The cases of 12 patients with SBH (3 men and 9 women; age
      range, 2-51 years) were evaluated on the basis of their MRI findings. Eight (18)F
      FDG PET and 12 (99m)Tc-ECD SPECT images were obtained. The uptakes of these
      images were compared with electroencephalography (EEG) or MRI findings such as
      band thickness. In all patients, easy Z-score Imaging System (eZIS) software was
      used to statistically analyze the SPECT images. RESULTS: Of the eight (18)F-FDG
      PET images, five showed higher uptake in the thick subcortical bands than in the
      overlying cortex. Of the 12 (99m)Tc-ECD SPECT examinations with eZIS images, nine
      indicated increased regional cerebral blood flow (rCBF) areas corresponding to
      the band locations. Of the eight (18)F-FDG PET examination findings, six were
      congruent with the rCBF distributions on the eZIS images. Eight of the 12
      patients showed correspondence to the increased rCBF on the eZIS images, the band
      locations on MRI, and abnormal discharge sites on EEG. CONCLUSIONS: Ectopic
      neurons in subcortical bands may have higher glucose metabolism and/or increased
      rCBF compared to the overlying cortex. (18)F-FDG PET and (99m)Tc-ECD SPECT using
      eZIS can be helpful to clearly detect the cellular activities of ectopic neurons
      in patients with SBH.

PMID- 23958595
TI  - Organic cation transporter 2 (SLC22A2), a low-affinity and high-capacity choline
      transporter, is preferentially enriched on synaptic vesicles in cholinergic
      neurons.
AB  - Organic cation transporters (OCTs) are expressed mainly in the kidney and liver.
      OCTs transport intrinsic organic cations, including monoamine, dopamine,
      serotonine and choline, across the plasma membrane. Here, we demonstrate that
      OCT2 (SLC22A2) is expressed in cholinergic neurons, motoneurons in the anterior
      horn of the spinal cord, and is implicated in acetylcholine (Ach) recycling in
      presynaptic terminals. Application of rabbit anti-peptide antibody revealed that
      OCT2 was expressed in the anterior horn of the spinal cord. Double immunostaining
      of muscle sections with anti-OCT2 and alpha-bungarotoxin (BTX) revealed that OCT2
      was localized in the neuromuscular junctions (NMJs). Immunoelectron microscopy
      revealed that OCT2 was localized both in synaptic vesicles (SVs) in presynaptic
      terminals around the motoneurons (C-terminals) and in SVs in nerve terminals in
      NMJs. The similarity in the distribution of OCT2 in cholinergic neurons and that
      of vesicular acetyl choline transporter (VAchT), and the fact that OCT2 can
      transport choline suggest that OCT2 could work as a low-affinity and high
      capacity choline transporter at presynaptic terminals in cholinergic neurons in a
      firing-dependent manner.

PMID- 23958596
TI  - Role of N-glycosylation of human lysosomal phospholipase A2 for the formation of
      catalytically active enzyme.
AB  - To understand the role of N-glycosylation of lysosomal phospholipase A2 (LPLA2),
      four potential N-glycosylation sites in human LPLA2 (hLPLA2) were individually
      modified replacing asparagine (Asn) with alanine by site-direct mutagenesis. COS
      7 cells transiently transfected with wild-type (WT) hLPLA2 gene produced
      catalytically active LPLA2. A single mutation at 273-, 289-, or 398-Asn partially
      reduced production of active LPLA2. A single mutation at 99-Asn and quadruple
      mutations at all four Asn sites resulted in a marked reduction of active LPLA2
      and loss of active LPLA2, respectively. Western blot analysis using anti-hLPLA2
      antibody showed that the LPLA2 expression level was similar between all
      transfectants. N-glycosidase F digestion revealed that multiple forms of LPLA2
      found in individual transfectants are due to different N-glycans linked to the
      core protein. The LPLA2 activity in individual transfectants was mostly recovered
      in the soluble fraction and correlated to the quantity of LPLA2 detected in the
      soluble fraction. LPLA2 mutated at 99-Asn was mostly retained in the membrane
      fraction. The WT transfectants treated with tunicamycin markedly lost LPLA2
      activity. These data indicate that the 99-Asn is the most critical N
      glycosylation site for formation of native hLPLA2 in vivo and that the N
      glycosylation of LPLA2 is crucial for biosynthesis of catalytically active
      hLPLA2. 

PMID- 23958597
TI  - Pro-HEART - a randomized clinical trial to test the effectiveness of a high
      protein diet targeting obese individuals with heart failure: rationale, design
      and baseline characteristics.
AB  - There is ample research to support the potential benefits of a high protein diet
      on clinical outcomes in overweight/obese, diabetic subjects. However, nutritional
      management of overweight/obese individuals with heart failure (HF) and type 2
      diabetes mellitus (DM) or metabolic syndrome (MS) is poorly understood and few
      clinical guidelines related to nutritional approaches exist for this subgroup.
      This article describes the design, methods, and baseline characteristics of study
      participants enrolled in Pro-HEART, a randomized clinical trial to determine the
      short term and long term effects of a high protein diet (30% protein [~110
      g/day], 40% carbohydrates [150 g/day], 30% fat [~50 g/day]) versus a standard
      protein diet (15% protein [~55 g/day], 55% carbohydrates [~200 g/day], 30% fat
      [~50 g/day]) on body weight and adiposity, cardiac structure and function,
      functional status, lipid profile, glycemic control, and quality of life. Between
      August, 2009 and May, 2013, 61 individuals agreed to participate in the study; 52
      (85%) - mean age 58.2 +/- 9.8 years; 15.4% Blacks; 57.7% Whites; 19.2% Hispanics;
      7.7% Asians; 73.1% male; weight 112.0 +/- 22.6 kg - were randomized to a 3-month
      intensive weight management program of either a high protein or standard protein
      diet; data were collected at baseline, 3 months, and 15 months. This study has
      the potential to reveal significant details about the role of macronutrients in
      weight management of overweight/obese individuals with HF and DM or MS.

PMID- 23958598
TI  - A developmental study on the neural circuitry mediating response flexibility in
      bipolar disorder.
AB  - Cross-sectional neuroimaging studies are an important first step in examining
      developmental differences in brain function between adults and youth with bipolar
      disorder (BD). Impaired response flexibility may contribute to reduced ability to
      modify goal-directed behavior in BD appropriately. We compared neural circuitry
      mediating this process in child (CBD) vs. adult BD (ABD) and age-matched healthy
      subjects. fMRI data from 15 CBD, 23 ABD, 20 healthy children, and 27 healthy
      adults were acquired during a response flexibility paradigm, a task where
      subjects inhibit a prepotent response and execute an alternative response. When
      successfully executing an alternate response, CBD showed frontal, parietal, and
      temporal hyperactivation relative to healthy children and ABD, while ABD
      hypoactivated these regions relative to healthy adults. Previous studies of
      response flexibility in healthy volunteers revealed frontal, temporal, and
      parietal cortex hyperactivation in children and hypoactivation in adults.
      Relative to age-matched healthy subjects, we found hyperactivation in these
      regions in CBD and hypoactivation in ABD. This suggests that our findings in
      patients may represent the extreme extension of the age-related response
      flexibility activation differences found in healthy subjects. Future studies
      should use longitudinal fMRI to examine the developmental trajectory of the
      neural circuitry mediating response flexibility in BD.

PMID- 23958599
TI  - From NAFLD to NASH to cirrhosis-new insights into disease mechanisms.
AB  - NAFLD has evolved as a serious public health problem in the USA and around the
      world. In fact, NASH-the most serious form of NAFLD-is predicted to become the
      leading cause of liver transplantation in the USA by the year 2020. The
      pathogenesis of NAFLD and NASH, in particular the mechanisms responsible for
      liver injury and fibrosis, is the result of a complex interplay between host and
      environmental factors, and is at the centre of intense investigation. In this
      Review, we focus on recently uncovered aspects of the genetic, biochemical,
      immunological and molecular events that are responsible for the development and
      progression of this highly prevalent and potentially serious disease. These
      studies bring new insight into this complex disorder and have led to the
      development of novel therapeutic and diagnostic strategies that might enable a
      personalized approach in the management of this disease. 

PMID- 23958601
TI  - Advances in the medical management of paediatric IBD.
AB  - IBD includes two classic entities, Crohn's disease and ulcerative colitis, and a
      third undetermined form (IBD-U), characterized by a chronic relapsing course
      resulting in a high rate of morbidity and impaired quality of life. Children with
      IBD are vulnerable in terms of growth failure, malnutrition and emotional
      effects. The aims of therapy have now transitioned from symptomatic control to
      the achievement of mucosal healing and deep remission. This type of therapy has
      been made possible by the advent of disease-modifying drugs, such as biologic
      agents, which are capable of interrupting the inflammatory cascade underlying
      IBD. Biologic agents are generally administered in patients who are refractory to
      conventional therapies. However, there is growing support that such agents could
      be used in the initial phases of the disease, typically in paediatric patients,
      to interrupt and cease the inflammatory process. Until several years ago, most
      therapeutic programmes in paediatric patients with IBD were borrowed from adult
      trials, whereas paediatric studies were often retrospective and uncontrolled.
      However, guidelines on therapeutic management of paediatric IBD and controlled,
      prospective, randomized trials including children with IBD have now been
      published. Here, the current knowledge concerning treatment options for children
      with IBD are reported. We also highlight the effectiveness and safety of new
      therapeutic advances in these paediatric patients. 

PMID- 23958600
TI  - The Gordian Knot of dysbiosis, obesity and NAFLD.
AB  - The development of obesity and NAFLD is known to be determined by host genetics,
      diet and lack of exercise. In addition, the gut microbiota has been identified to
      influence the development of both obesity and NAFLD. Evidence for the role of the
      gut microbiota has been shown by preclinical studies of transfer of gut
      microbiota from lean and obese individuals, with the recipient developing the
      metabolic features of the donor. Many bidirectional interactions of the gut
      microbiota, including with food, bile and the intestinal epithelium, have been
      identified. These interactions might contribute to the distinct steps in the
      progression from lean to obese states, and to steatosis, steatohepatitis and
      eventually fibrosis. The predominant steps are efficient caloric extraction from
      the diet, intestinal epithelial damage and greater entry of bacterial components
      into the portal circulation. These steps result in activation of the innate
      immune system, liver inflammation and fibrosis. Fortunately, therapeutic
      interventions might not require a full understanding of these complex
      interactions. Although antibiotics are too unselective in their action,
      probiotics have shown efficacy in reversing obesity and NASH in experimental
      systems, and are under investigation in humans. 

PMID- 23958602
TI  - Viral hepatitis: Cost-effectiveness of direct-acting antivirals for chronic
      hepatitis C.
AB  - A new study has reported the long-term effectiveness and cost-effectiveness of
      the direct-acting antivirals telaprevir and boceprevir for the treatment of
      chronic hepatitis C. These findings have the potential to be used to guide
      clinical and reimbursement decisions for treating populations with a high
      prevalence of HCV infection.

PMID- 23958603
TI  - NAFLD: Profiling NAFLD--liver gene expression and DNA methylation patterns to
      characterize disease severity.

PMID- 23958604
TI  - The experience of presence among telehealth nurses.
AB  - BACKGROUND: Telehealth technology allows for the provision of nursing care even
      when the patient and nurse are physically separated from each other. Telehealth
      has shown positive effects on healthcare costs and healthcare access. Although it
      can increase healthcare access and decrease healthcare costs, the use of
      telehealth has altered the typical pattern of nurse-patient proximity. It is
      unknown how the physical separation related to telehealth use may affect the
      experience of presence among nurses during nurse-patient interactions. PURPOSE:
      The purpose of the research was to gain knowledge about the ways that nurses
      experience presence during interactions with patients using telehealth
      technology. METHODS: A qualitative descriptive design with convenience sampling
      was used for this study. Sample inclusion criteria included being a registered
      nurse with at least 1 year of experience using telehealth technology and working
      in telehealth at the time of the study. Institutional review board approval was
      received before beginning data collection. Participants (n = 6) provided informed
      consent. Qualitative data were obtained by individual, audiotaped, semistructured
      interviews. The data were transcribed and analyzed deductively for the existence
      of presence. Ethnograph version 6.0 software was used to assist in organizing and
      analyzing the data. RESULTS: Two examples of presence during telehealth nurse
      patient interactions were described by participants. CONCLUSION: This study
      documented for the first time the experience of presence among nurses who
      interact with their patients using only nonvideo telehealth technology.

PMID- 23958605
TI  - Relationships among self-efficacy, depression, life satisfaction, and adaptation
      among older korean adults residing in for-profit professional nursing facilities.
AB  - BACKGROUND: Adapting to a new environment is especially difficult for older
      adults relocating into professional nursing facilities or other specialized care
      centers. This relocation is a prominent life stressor in older adults. PURPOSE:
      This study examined the self-efficacy, depression, life satisfaction, and
      adaptation and the relationships among these four variables of older Korean
      adults residing in for-profit professional nursing facilities to provide
      preliminary information necessary to improve nursing interventions. METHODS: This
      was a cross-sectional and descriptive correlation study. The 322 participants
      were all over the age of 65 years and resided in one of three different for
      profit professional nursing facilities in Seoul and Gyeonggi-do, South Korea.
      Measures used included a demographic characteristics form, Self-Efficacy
      Instrument, Korean Simple Depression Scale, Standard Life Satisfaction
      Instrument, and Facility Adaption Scale. RESULTS: Results found positive self
      efficacy, depression, life satisfaction, and adaptation among participants. We
      found significant positive correlations among self-efficacy, life satisfaction,
      and adaptation and significant negative correlations among depression, life
      satisfaction, and adaptation. Moreover, we found noticeable differences in the
      degree of adaptation to professional nursing facility placement in several
      variables, including gender, age, level of education, religious background,
      perceived health status, presence of a spouse, presence of a nonprofessional
      caregiver(s), and decision maker. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: This
      cross-sectional study provides preliminary evidence that older Korean adults in
      for-profit professional nursing facilities generally maintain a healthy level of
      well-being. However, nursing interventions to improve self-efficacy and life
      satisfaction and decrease depression in older adult residents are needed to help
      these older adults adapt to life in such facilities.

PMID- 23958606
TI  - Personal resource questionnaire: a systematic review.
AB  - BACKGROUND: Social support is a key nursing variable. No review has yet
      systematically assessed the effectiveness of the personal resource questionnaire
      (PRQ) as a measure of perceived social support. PURPOSE: This article reviewed
      nine previous studies that used the PRQ (Brandt & Weinert, 1981). METHODS:
      Completed studies were identified through searches of indexes that included
      PubMed, the Cumulative Index for Nursing and EBSCO host, and Ovid. Studies that
      reported PRQ scores, sample descriptions, and sample sizes and that tested the
      relationship between the PRQ and study variables were included in the present
      review. Three other studies were included that did not report on PRQ correlations
      with other health variables. The included studies addressed a variety of health
      problems and different population in different settings. RESULTS: Cronbach's
      alphas for the included studies ranged from .87 to .93, supporting the internal
      consistency of the PRQ. Hypothesized relationships between the PRQ and study
      variables including health promotion behavior, self-care behavior, self-efficacy,
      self-esteem, stress, depression, loneliness, pain, and disability were supported,
      providing positive evidence for PRQ construct validity. Included studies used the
      PRQ to address disparate populations in terms of age, socioeconomic status,
      ethnicity, and educational background. CONCLUSION: This review found the PRQ to
      be a reliable and valid tool for measuring perceived social support across a wide
      range of populations. Further studies are necessary to examine the relationship
      between social support and selected demographics among populations with different
      cultural backgrounds.

PMID- 23958607
TI  - Effectiveness of integrated body-mind-spirit group intervention on the well-being
      of Indian patients with depression: a pilot study.
AB  - BACKGROUND: Depression is a leading cause of disability worldwide. There is a
      need to develop effective strategies to treat depression and prevent recurrence.
      Treatments that combine pharmacological and psychotherapeutic approaches are
      preferred for treating severe forms of depression. PURPOSE: The study assesses
      the effect of an integrated body-mind-spirit group intervention in patients with
      depression. METHODS: This pilot study was a pretest-posttest design study. Thirty
      adult patients diagnosed with depression attending the psychiatric outpatient
      department at a district hospital were randomly assigned to either the
      intervention group or comparison group. Each group had 15 patients. The
      intervention group received both the intervention and routine hospital treatment
      and underwent four group integrated body-mind-spirit group intervention therapy
      sessions. These sessions were held once per week on either Saturday or Sunday,
      with each session lasting more than 3 hours. Comparison group participants
      received routine hospital treatment only. Outcome measures, including level of
      depression, well-being, and work and social adjustment, were measured using the
      Beck Depression Inventory-II, body-mind-spirit well-being scale, and work and
      social adjustment scale. Both groups were evaluated at baseline, 1 month, 2
      months, and 3 months. RESULTS: Results showed that both groups had significant
      reductions in the level of depression, improvements in well-being, and work and
      social adjustment at 3-month follow-up compared with baseline. In addition, the
      intervention group showed significant mean differences in levels of depression,
      well-being, and work and social adjustment compared with the comparison group.
      CONCLUSION: The integrated body-mind-spirit group intervention model appears to
      reduce depressive symptoms and improve well-being in patients with depression.

PMID- 23958608
TI  - Comparing the antiswelling and analgesic effects of three different ice pack
      therapy durations: a randomized controlled trial on cases with soft tissue
      injuries.
AB  - BACKGROUND: Ice pack therapy has been widely used in treatment for soft tissue
      injuries. However, no studies have yet explored the most appropriate and
      effective duration for ice therapy with ice packs. PURPOSE: This study explored
      the antiswelling and analgesic effects of different ice pack therapy durations on
      soft tissue injuries as well as patient discomfort. METHODS: An experimental
      design including pretest and three posttests with three groups was used in this
      study. Using convenience sampling and randomized block assignment, 99
      participants with soft tissue injuries from the emergency department of a medical
      center in southern Taiwan were included in this study. With 33 participants in
      each group, three groups with ice pack therapy for 10, 20, and 30 minutes were
      indicated to compare skin temperature, swelling, and pain differences in ice
      treated areas as well as participant discomfort. RESULTS: This study found no
      significant differences in the effect of different ice pack therapy durations
      among the three groups. However, this study identified significant differences
      between pretest and each posttest in terms of changes in skin temperature, pain,
      and numbness and rash-related discomfort in each group. CONCLUSION/IMPLICATIONS
      FOR PRACTICE: Research results found that the three different ice pack therapy
      durations could lower skin temperature and reduce partial pain. The different ice
      pack therapy durations would cause similar discomfort incidence rates in the
      three groups. Ice pack therapy for 10 minutes could reduce partial swelling and
      pain effectively. Accordingly, we suggest that 10 minutes is the optimal ice pack
      therapy duration for persons with soft tissue injuries. However, the ice pack
      therapy duration should be adjusted according to individual needs and situation.

PMID- 23958609
TI  - Relationship between media viewing and obesity in school-aged children in Taipei,
      Taiwan.
AB  - BACKGROUND: Increased media viewing such as watching television and videos and
      playing on/using computers has been associated with childhood obesity. Guidelines
      from the American Academy of Pediatrics recommend limiting children's total media
      time to no more than 2 hours per day. Information about media usage and school
      aged obesity in Taiwan is lacking. PURPOSE: The purpose of this study was to
      investigate whether media viewing after school is associated with the total and
      centralobesity in school-aged children in Taipei, Taiwan's capital and largest
      city. METHODS: A case-control study was designed, and a control approach was used
      to recruit participants. Two hundred seventy-five obese and 275 normal-weight
      children currently in the fourth grade were enrolled from 29 elementary schools
      in Taipei City. Media viewing after school was measured using a 3-day self
      reported physical activity log and the daily sedentary activity component of the
      National Health Interview Survey in Taiwan. The latter was completed by the
      participants' parents. RESULTS: Participants with total obesity had significantly
      more television watching time (60.24 minutes vs. 43.50 minutes, p < .05) and
      total media watching time (73.61 minutes vs. 52.67 minutes, p < .001) than normal
      weight participants. Similar results were found for participants with central
      obesity. Total television and total media watching durations greater than 2 hours
      a day correlated significantly with total and central obesity. Time spent using
      computers did not differ significantly between obese and normal-weight control
      participants on weekdays. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Childhood
      obesity may be multifactorial in origin. Excessive sedentary activity such as
      watching television may have a variety of consequences beyond the putative effect
      on body habitus. School nurses should promote health programs targeted to prevent
      excessive weight and obesity in children, recommend reducing media viewing, and
      encourage patient participation in extracurricular outdoor activities.

PMID- 23958610
TI  - Identifying critical thinking indicators and critical thinker attributes in
      nursing practice.
AB  - BACKGROUND: Critical thinking is an essential skill in the nursing process.
      Although several studies have evaluated the critical thinking skills of nurses,
      there is limited information related to the indicators of critical thinking or
      evaluation of critical thinking in the context of the nursing process. PURPOSE:
      This study investigated the potential indicators of critical thinking and the
      attributes of critical thinkers in clinical nursing practice. Knowledge of these
      indicators can aid the development of tools to assess nursing students' critical
      thinking skills. METHODS: The study was conducted between September 2009 and
      August 2010. In phase 1, a literature review and four focus groups were conducted
      to identify the indicators of critical thinking in the context of nursing and the
      attributes of critical thinkers. In phase 2, 30 nursing professionals
      participated in a modified Delphi research survey to establish consensus and the
      appropriateness of each indicator and attribute identified in phase 1. RESULTS:
      We identified 37 indicators of critical thinking and 10 attributes of critical
      thinkers. The indicators were categorized into five subscales within the context
      of the nursing process toreflect nursing clinical practice: assessment, 16
      indicators of ability to apply professional knowledge and skills to analyze and
      interpret patient problems; diagnosis, five indicators of ability to propose
      preliminary suppositions; planning, five indicators of ability to develop problem
      solving strategies; implementation, five indicators of ability to implement
      planning; and evaluation, six indicators of ability to self-assess and reflect.
      CONCLUSION/IMPLICATIONS FOR PRACTICE: The study operationalized critical thinking
      into a practical indicator suitable for nursing contexts in which critical
      thinking is required for clinical problem solving. Identified indicators and
      attributes can assist clinical instructors to evaluate student critical thought
      skills and development-related teaching strategies.

PMID- 23958611
TI  - Developing and psychometric testing of a short-form problem areas in diabetes
      scale in chinese patients.
AB  - BACKGROUND: The 20-item Problem Areas in Diabetes (PAID) scale is widely used to
      measure diabetes-related emotional distress. The short-form PAID scale is helpful
      for the rapid screening of diabetes-related emotional distress in clinical
      settings. PURPOSE: This study developed and examined the psychometric properties
      of a short-form Chinese-version PAID (SF-PAID-C) scale. METHODS: The Chinese
      version 20-item PAID (PAID-C) scale was administered to 855 patients with type 2
      diabetes mellitus. Item analysis, exploratory factor analysis, and
      confirmatoryfactoranalysis were then applied to develop the SF-PAID-C and
      evaluate its construct validity. The correlations between SF-PAID-C and the
      latest HbA1c close to the measurement of PAID-C (baseline HbA1c) 3 months and 12
      months later were used to examine the concurrent and predictive validity of the
      SF-PAID-C. Receiver operating characteristic curve analysis was used to examine
      the sensitivity and specificity of the SF-PAID-C. Cronbach's alpha was used to
      assess internal consistency. Test-retest on 24 patients was used to examine the
      stability of the SF-PAID-C. RESULTS: An 8-item SF-PAID-C was developed. The SF
      PAID-C significantly correlated with the PAID-C (r = .941, p < .001), baseline
      HbA1c (r = .148, p < .001), 3-month HbA1c (r = .147, p < .001), and 12-month
      HbA1c (r = .142, p < .001). The sensitivity and specificity of the SF-PAID-C were
      93.2% and 94.2%, respectively. The Cronbach's alpha and test-retest reliability
      of the SF-PAID-C were .85 and .93, respectively. CONCLUSIONS/IMPLICATIONS FOR
      PRACTICE: The SF-PAID-C is a reliable and valid scale that can be used to screen
      for diabetes-related emotional problem in Chinese patients with type 2 diabetes
      mellitus in clinical settings.

PMID- 23958612
TI  - Preliminary study: Taiwanese mothers' experiences of children with sensory
      processing disorder.
AB  - BACKGROUND: Different cultural backgrounds and parental experiences influence
      parenting styles and approaches to raising children with disabilities. Family
      centered care should consider parental, especially main caregivers, experiences
      with their disabled children. In Taiwan, in most of homes, mothers are the main
      caregivers. PURPOSE: The purpose of this study was to explore Taiwanese mothers'
      experiences with their children who have sensory processing disorder. METHODS:
      This study used a qualitative ethnographic design and semistructured interview
      format. Transcripts were analyzed and synthesized into themes. RESULTS: Three
      mothers were interviewed. The following three themes emerged: (a) relationships
      within the shared worlds of disability and culture, (b) daily life challenges and
      expectations, and (c) opportunity to receive professional services. These
      Taiwanese mothers expressed that they experienced stress from being blamed for
      insufficient skills and from the shame of their children's disabilities that
      reflected lack of teacher, friend, and other family members' understanding of the
      cause of their children's inappropriate behaviors. Their children experienced
      difficulties performing daily activities, which resulted in stresses on both the
      mother and her child. The interviewed mothers needed to receive timely, long-term
      services from healthcare professionals. However, hospitals are inadequately
      staffed with occupational therapists, which delays care for children with special
      needs. CONCLUSION: Taiwanese mothers experience stresses from themselves, their
      child, and others. Healthcare professionals should apply a family-centered
      service approach to fulfill the needs of mothers and their disabled children.
      Moreover, healthcare professionals should promote greater awareness of sensory
      processing disorder symptoms and interventions to increase public awareness and
      acceptance of these children.

PMID- 23958613
TI  - The effects of contextual and structural factors on patient safety in nursing
      units.
AB  - BACKGROUND: Because of limited research on patient safety from a macrolevel
      perspective, our understanding of how to reduce the risk of system failures that
      impact patient safety outcomes in Taiwanese healthcare organizations is limited.
      PURPOSE: We conducted this study to explore the relationships between macrolevel
      factors and patient safety outcomes. METHODS: Structural contingency theory was
      used as the framework for the study. A cross-sectional design was used, and data
      were collected from self-administered questionnaires. Head nurses and registered
      nurses working in 64 in-patient nursing units at three hospitals participated in
      the study. A tailored design method was used for data collation, and the data
      collection lasted 3 weeks during the winter of 2010. Data were aggregated from
      the individual to the unit level, and path analysis was used to examine the
      hypothesized model. RESULTS: Sixty-two head nurses (96.8%) and 977 staff nurses
      (72%) completed and returned the questionnaire. Eta-squared coefficient (eta),
      interitem consistency (rwg), and F ratio results showed that data at the
      individual level are appropriate for aggregating to the unit level. These
      findings show that nursing units with high degrees of professional autonomy,
      comparatively higher proportions of nursing experts, and relatively large unit
      sizes tend to have higher rates of medication errors. In addition, we found high
      degrees of unit technology associated with higher rates of medication errors and
      patient falls. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: These findings suggest a
      link between macrolevel factors and patient safety outcomes. This study shows
      that redesigning continuing education programs encourages nurses to participate
      in patient safety training and understand the nursing unit characteristics that
      enhance patient safety outcomes to improve the patient safety of nursing units.

PMID- 23958614
TI  - Incompetent? Really?

PMID- 23958615
TI  - Should prophylactic antibiotics be routinely given to a mother before a cesarean
      birth?

PMID- 23958617
TI  - Mothers' descriptions of recovery from postpartum depression.
AB  - PURPOSE: To describe the experience of women who perceived themselves as having
      recovered from postpartum depression (PPD). STUDY DESIGN: This study was a
      qualitative, naturalistic inquiry design with in-depth participant interviews.
      METHOD: Nine women who had been medically diagnosed with PPD and self-identified
      as recovered from PPD served as participants. The method used was the constant
      comparison of data for discovery of thematic junctures. Women were recruited
      through their healthcare provider and through the snowball method. RESULTS: Four
      thematic junctures were identified during the recovery from PPD: prelude to
      recovery, igniting recovery, recovery recounted as a victory, and realizing
      recovery was achieved. Moving through these junctures was an iterative process.
      CLINICAL IMPLICATIONS: The women in this study were able to describe a process of
      recovery from PPD. This occurred at the time when they were able to identify
      thoughts, feelings, and behaviors that embodied the acquisition of a successful
      maternal identity. Knowing this, nurses should support women to achieve their
      maternal identity and use this knowledge to manage, and recover from, PPD.

PMID- 23958618
TI  - Exploration of reasons for feeding choices in Hispanic mothers.
AB  - PURPOSE: To explore factors that contribute to feeding choices Hispanic women
      make for their newborn infants in the immediate postpartum period, with a focus
      on the phenomenon of "los dos," breastfeeding with formula supplementation. STUDY
      DESIGN AND METHODS: A descriptive qualitative design that utilized a
      semistructured interview guide with open-ended questions was used. Qualitative
      data preparation and analysis methods were used to identify themes surrounding
      feeding choices. The sample included 19 women within 48 hours of giving birth who
      self-identified as Spanish speakers. RESULTS: Reasons included 1) previous
      experience; 2) "no llora con hambre" (no crying for hunger); 3) "para salud" (for
      health); and 4) to prevent suffering that might occur when the mother and infant
      were separated while the mother worked "no quiero que sufra mientras trabajo."
      CLINICAL IMPLICATIONS: Discussion of infant feeding choices should occur prior to
      birth since many mothers decide on feeding method while still pregnant. At the
      first prenatal visit identification of preference should occur to include not
      just breast or formula, but also asking about "los dos." Educational
      interventions that directly address the "los dos" feeding practice should be
      culturally appropriate, evaluated and disseminated for use in the prenatal
      period. Influential family members should be included in prenatal visits and
      educational sessions to help assure that the woman is not receiving mixed
      messages at home. Assessment of the workplace environment should also occur
      during the prenatal period with an exploration of how pumping and storing of
      breast milk might be possible once women return to work after the baby's birth.

PMID- 23958620
TI  - Breastfeeding concerns and experiences of African American mothers.
AB  - OBJECTIVE: To explore the perinatal experiences of African American women in
      Florida for obtaining information about breastfeeding and also their
      breastfeeding experiences. METHODS: This qualitative study utilized convenience
      sampling of 253 African American women 18 to 35 years old in three Florida
      counties. Data were derived from the Healthy Futures Perinatal Research and
      System Design study. One month after giving birth, face-to face interviews were
      conducted using an interview schedule. Questions about breastfeeding education
      and experiences were explored. Taped responses were transcribed and analyzed
      qualitatively. Through subject-level content analysis, key themes were
      identified. RESULTS: Most women received some information about breastfeeding
      during prenatal care. Mothers who chose to breastfeed were usually aware of some
      of the benefits for the baby and occasionally benefits for themselves. Mothers
      who did not breastfeed were concerned about pain associated with breastfeeding,
      time constraints, returning to work or school, personal health choices, or felt
      uncomfortable with the idea of breastfeeding. Factors facilitating breastfeeding
      included healthcare providers that encouraged the practice, knowing the
      advantages, attending a breastfeeding class or support group, breastfeeding in
      the birth or recovery room, latch assistance, rooming-in, nesting, and the
      availability of a breast pump. Reasons for supplementation and cessation were
      latch problems, pain, concerns the baby wasn't getting enough, mother-infant
      separation, and medical complications. IMPLICATIONS: Intensified prenatal and
      postpartum efforts to support breastfeeding are needed to increase breastfeeding
      initiation and duration for African American mothers.

PMID- 23958622
TI  - Personalized nutrition: has its time come?

PMID- 23958623
TI  - Speech recognition for nursing documentation.

PMID- 23958624
TI  - Bolsa Familia: reaching Brazil's poorest of the poor.

PMID- 23958626
TI  - Planned home birth.

PMID- 23958629
TI  - Use of the MCNPX to calculate the neutron spectra around the GE-PETtrace 8
      cyclotron of the CDTN/CNEN, Brazil.
AB  - The Monte Carlo code MCNPX was used to calculate the neutron spectra in 4 points
      around the targets of the CDTN/CNEN cyclotron, Belo Horizonte, Brazil, during the
      production of the (18)FDG. Simulated data were compared with experimental data
      obtained with a Bonner multisphere spectrometry system (BSS) using TLD-600 and
      TLD-700 and the unfolding codes BUNKIUT, BUMS and NSDUAZ. In general, simulated
      spectra disagreed with those obtained by experimental means by a factor as high
      as 14. Measurements performed with a doserate meter in other 3 more shielded
      points, showed also an overestimation of the ambient dose equivalent rate by a
      factor as high as 20 in comparison with simulated results. Results are not
      conclusive and a more refined study is necessary. However, neutron emission rate
      of the source-term of radiation must be investigated and an special caution must
      be taken in the experimental measurements, by discriminating of the target
      selected for the irradiations and utilizing a matrix response suitable for the
      passive detectors (e.g. TLD) utilized in the experiments, instead of a matrix
      response (e.g. UTA4) developed for scintillation detectors. 

PMID- 23958628
TI  - Tobacco in the Arab world: old and new epidemics amidst policy paralysis.
AB  - The Arab world is comprised of 22 countries with a combined population of ~360
      million. The region is still at the initial stages of the tobacco epidemic, where
      it is expected to witness an increase in smoking levels and mounting tobacco
      related morbidity and mortality in the future. Still, the bleak outlook of the
      tobacco epidemic in the Arab world continues to be faced with complacency in the
      form of underutilization of surveillance systems to monitor the tobacco epidemic
      and prioritize action, and failure to implement and enforce effective policies to
      curb the tobacco epidemic. Understandably, the focus on the Arab world carries
      the risk of trying to generalize to such a diverse group of countries at
      different level of economic and political development. Yet, tobacco control in
      the Arab world faces some shared patterns and common challenges that need to be
      addressed to advance its cause in this region. In addition, forces that promote
      tobacco use, such as the tobacco industry, and trends in tobacco use, such as the
      emerging waterpipe epidemic tend to coalesce around some shared cultural and
      socio-political features of this region. Generally, available data from Arab
      countries point at three major trends in the tobacco epidemic: (1) high
      prevalence of cigarette smoking among Arab men compared with women; (2) the re
      emergence of waterpipe (also known as hookah, narghile, shisha, arghile) smoking
      as a major tobacco use method, especially among youth and (3) the failure of
      policy to provide an adequate response to the tobacco epidemic. In this review,
      we will discuss these trends, factors contributing to them, and the way forward
      for tobacco control in this unstable region. 

PMID- 23958630
TI  - QUANTIFYING REGIONAL GROWTH PATTERNS THROUGH LONGITUDINAL ANALYSIS OF DISTANCES
      BETWEEN MULTIMODAL MR INTENSITY DISTRIBUTIONS.
AB  - Quantitative analysis of early brain development through imaging is critical for
      identifying pathological development, which may in turn affect treatment
      procedures. We propose a framework for analyzing spatiotemporal patterns of brain
      maturation by quantifying intensity changes in longitudinal MR images. We use a
      measure of divergence between a pair of intensity distributions to study the
      changes that occur within specific regions, as well as between a pair of
      anatomical regions, over time. The change within a specific region is measured as
      the contrast between white matter and gray matter tissue belonging to that
      region. The change between a pair of regions is measured as the divergence
      between regional image appearances, summed over all tissue classes. We use kernel
      regression to integrate the temporal information across different subjects in a
      consistent manner. We applied our method on multimodal MRI data with T1-weighted
      (T1W) and T2-weighted (T2W) scans of each subject at the approximate ages of 6
      months, 12 months, and 24 months. The results demonstrate that brain maturation
      begins at posterior regions and that frontal regions develop later, which matches
      previously published histological, qualitative and morphometric studies. Our
      multimodal analysis also confirms that T1W and T2W modalities capture different
      properties of the maturation process, a phenomena referred to as T2 time lag
      compared to T1. The proposed method has potential for analyzing regional growth
      patterns across different populations and for isolating specific critical
      maturation phases in different MR modalities.

PMID- 23958635
TI  - Use of twitter among local health departments: an analysis of information
      sharing, engagement, and action.
AB  - BACKGROUND: Social media offers unprecedented opportunities for public health to
      engage audiences in conversations and collaboration that could potentially lead
      to improved health conditions. While there is some evidence that local health
      departments (LHDs) are using social media and Twitter in particular, little is
      known about how Twitter is used by LHDs and how they use it to engage followers
      versus disseminating one-way information. OBJECTIVE: To examine how LHDs use
      Twitter to share information, engage with followers, and promote action, as well
      as to discover differences in Twitter use among LHDs by size of population
      served. METHODS: The Twitter accounts for 210 LHDs were stratified into three
      groups based on size of population served (n=69 for less than 100,000; n=89 for
      100,000-499,999; n=52 for 500,000 or greater). A sample of 1000 tweets was
      obtained for each stratum and coded as being either about the organization or
      about personal-health topics. Subcategories for organization included
      information, engagement, and action. Subcategories for personal health included
      information and action. RESULTS: Of all LHD tweets (n=3000), 56.1% (1682/3000)
      related to personal health compared with 39.5% (1186/3000) that were about the
      organization. Of the personal-health tweets, 58.5% (984/1682) involved factual
      information and 41.4% (697/1682) encouraged action. Of the organization-related
      tweets, 51.9% (615/1186) represented one-way communication about the organization
      and its events and services, 35.0% (416/1186) tried to engage followers in
      conversation, and 13.3% (158/1186) encouraged action to benefit the organization
      (eg, attend events). Compared with large LHDs, small LHDs were more likely to
      post tweets about their organization (Cramer's V=0.06) but were less likely to
      acknowledge events and accomplishments of other organizations (chi2=12.83, P=.02,
      Cramer's V=0.18). Small LHDs were also less likely to post personal health
      related tweets (Cramer's V=0.08) and were less likely to post tweets containing
      suggestions to take action to modify their lifestyle. While large LHDs were more
      likely to post engagement-related tweets about the organization (Cramer's
      V=0.12), they were less likely to ask followers to take action that would benefit
      the organization (chi2=7.59, P=.02. Cramer's V=0.08). While certain associations
      were statistically significant, the Cramer's V statistic revealed weak
      associations. CONCLUSIONS: Twitter is being adopted by LHDs, but its primary use
      involves one-way communication on personal-health topics as well as organization
      related information. There is also evidence that LHDs are starting to use Twitter
      to engage their audiences in conversations. As public health transitions to more
      dialogic conversation and engagement, Twitter's potential to help form
      partnerships with audiences and involve them as program participants may lead to
      action for improved health.

PMID- 23958634
TI  - CATP is a critical component of the Neurospora circadian clock by regulating the
      nucleosome occupancy rhythm at the frequency locus.
AB  - Rhythmic frq transcription is essential for the function of the Neurospora
      circadian clock. Here we show that there is a circadian histone occupancy rhythm
      at the frq promoter that is regulated by FREQUENCY (FRQ). Using a combination of
      forward genetics and genome sequencing, we identify Clock ATPase (CATP) as an
      essential clock component. Our results demonstrate that CATP associates with the
      frq locus and other WCC target genes and promotes histone removal at these loci
      to allow circadian gene transcription. These results indicate that the rhythmic
      control of histone occupancy at clock genes is critical for circadian clock
      function. 

PMID- 23958636
TI  - Sensitive label-free monitoring of protein kinase activity and inhibition using
      ferric ions coordinated to phosphorylated sites as electrocatalysts.
AB  - Ferric ions show high affinity to the kinase-generated phosphorylated sites of
      peptides. Thus, the high electrocatalytic activity of the coordinated ferric ions
      toward the reduction of hydrogen peroxide can be used for sensitive label-free
      monitoring of protein kinase activity and inhibition. 

PMID- 23958637
TI  - Structure of internalin InlK from the human pathogen Listeria monocytogenes.
AB  - Listeria monocytogenes is a human pathogen that employs a wide variety of
      virulence factors in order to adhere to, invade, and replicate within target
      cells. Internalins play key roles in processes ranging from adhesion to receptor
      recognition and are thus essential for infection. Recently, InlK, a surface
      associated internalin, was shown to be involved in Listeria's ability to escape
      from autophagy by recruitment of the major vault protein (MVP) to the bacterial
      surface. Here, we report the structure of InlK, which harbors four domains
      arranged in the shape of a "bent arm". The structure supports a role for the
      "elbow" of InlK in partner recognition, as well as of two Ig-like pedestals
      intercalated by hinge regions in the projection of InlK away from the surface of
      the bacterium. The unusual fold and flexibility of InlK could be essential for
      MVP binding and concealment from recognition by molecules involved in the
      autophagic process. 

PMID- 23958638
TI  - Probing light emission from quantum wells within a single nanorod.
AB  - Significant improvements in the efficiency of optoelectronic devices can result
      from the exploitation of nanostructures. These require optimal
      nanocharacterization techniques to fully understand and improve their
      performance. In this study we employ room temperature cathodoluminescence
      hyperspectral imaging to probe single GaN-based nanorods containing multiple
      quantum wells (MQWs) with a simultaneous combination of very high spatial and
      spectral resolution. We have investigated the strain state and carrier transport
      in the vicinity of the MQWs, demonstrating the high efficiencies resulting from
      reduced electric fields. Power-dependent photoluminescence spectroscopy of arrays
      of these nanorods confirms that their fabrication results in partial strain
      relaxation in the MQWs. Our technique allows us to interrogate the structures on
      a sufficiently small length scale to be able to extract the important
      information. 

PMID- 23958639
TI  - Inhibitory kinetics of chlorocinnamic acids on mushroom tyrosinase.
AB  - Tyrosinase (EC 1.14.18.1) is the key enzyme of most food enzymatic oxidation.
      Tyrosinase inhibitors are important in food industry. In the present paper, 2
      chlorcinnamic acid and 2,4-dichlorocinnamic acid were synthesized and the
      inhibitory kinetics on mushroom tyrosinase were investigated. The results showed
      that both compounds synthesized could inhibit tyrosinase activity. For
      monophenolase activity, both chlorocinnamic acids could extended the lag time and
      decrease the steady-state activities, 2-chlorcinnamic acid extended the lag time
      just by 5%, and 2,4-dichlorcinnamic acid extended the lag time more than by
      30.4%. For diphenolase activity, the IC50 values of 2-chlorcinnamic acid and 2,4
      dichlorocinnamic acid were determined to be 0.765 mM and 0.295 mM, respectively.
      The inhibition kinetics showed that 2-chlorcinnamic acid and 2,4-dichlorocinnamic
      acid displayed a reversible and uncompetitive mechanism. The inhibition constants
      were determined to be 0.348 mM and 0.159 mM, respectively. The research may
      supply the basis for designing new tyrosinase inhibitors. 

PMID- 23958640
TI  - Solid-state fermentation of Jatropha seed cake for optimization of lipase,
      protease and detoxification of anti-nutrients in Jatropha seed cake using
      Aspergillus versicolor CJS-98.
AB  - This study focused on the solid-state fermentation of Jatropha seed cake (JSC), a
      byproduct generated after biodiesel production. Presence of anti-nutritional
      compounds and toxins restricts its application in livestock feed. The disposal of
      the JSC is a major environmental problem in the future, due to the generation of
      huge quantity of JSC after biodiesel extraction. Hence the JSC was assessed for
      its suitability as substrate for production and optimization of lipase and
      protease from Aspergillus versicolor CJS-98 by solid-state fermentation (SSF).
      The present study was also focused on the biodetoxification of anti-nutrients and
      toxins in JSC. The SSF parameters were optimized for maximum production of lipase
      and protease. Under the optimized conditions, the JSC supplemented with maltose
      and peptone (2%), adjusted to pH 7.0, moisture content 40%, inoculated with 1 *
      10(7) spores per 5 g cake and incubated at 25 degrees C, produced maximum lipase,
      1288 U/g and protease, 3366 U/g at 96 h. The anti-nutrients like phytic acid
      (6.08%), tannins (0.37%), trypsin inhibitors (697.5 TIU/g), cyanogenic glucosides
      (692.5 MUg/100 g), and lectins (0.309 mg/ml), were reduced to 1.70%, 0.23%, 12.5
      TIU/g, 560.6 MUg/100 g and 0.034 mg/ml respectively. The main toxic compound
      phorbol esters content in the JSC was reduced from 0.083% to 0.015% after SSF.
      Our results indicate that viability of SSF to utilize the huge amount of seed
      cake generated after extraction of biodiesel, for production of industrial
      enzymes and biodetoxification of anti-nutrients, toxins. 

PMID- 23958641
TI  - Prospective associations between childhood low-level lead exposure and adult
      mental health problems: the Port Pirie cohort study.
AB  - Low-level environmental lead exposure during childhood is associated with poorer
      emotional/behavioural functioning in later childhood and adolescence. Scarce
      research has examined whether these apparent effects persist into adulthood. This
      study is the first to examine prospective associations between lead exposure
      across early childhood and several common adult mental health problems. Childhood
      data (including blood lead concentrations) and adult data (from mental health
      questionnaires and psychiatric interviews) were available for 210 participants
      (44% males, mean age=26.3 years) from the Port Pirie cohort study (1979-1982
      birth cohort). Participants had a mean childhood (to 7 years) average blood lead
      concentration of 17.2MUg/dL. Among females, childhood blood lead showed small
      significant positive associations with lifetime diagnoses of drug and alcohol
      abuse and social phobia, and with anxiety, somatic and antisocial personality
      problems. For example: for a 10MUg/dL blood lead increase, females were 2.84
      times (95% CI 1.10, 7.30) more likely to have an alcohol abuse diagnosis.
      However, adjustment for childhood covariates - particularly stimulation within
      the home environment - rendered these associations non-significant. No
      significant or sizeable unadjusted or adjusted associations were seen for males.
      The associations between early lead exposure and emotional/behavioural
      functioning in children might persist into adulthood, at least for females.
      However, it is unclear whether such results arise from residual confounding, or
      other mechanisms. Interventions that focus on improving the childhood home
      environment may have a long-term positive impact on adult mental health outcomes.
      However, more prospective research using large and representative samples is
      needed to substantiate these results. 

PMID- 23958643
TI  - Banning tobacco sales and advertisements near educational institutions may reduce
      students' tobacco use risk: evidence from Mumbai, India.
AB  - BACKGROUND: India's Cigarettes and Other Tobacco Products Act bans tobacco sales
      and advertisements within 100 yards of educational institutions. In school
      adjacent neighbourhoods in Mumbai, we assessed adherence to these policies and
      whether tobacco vendor and advertisement densities were associated with students'
      tobacco use. METHODS: High school students' tobacco use was measured using a
      multistage cluster sampling survey (n=1533). Field geographic information systems
      data were obtained for all tobacco vendors and advertisements within 500 m of
      schools (n=26). Random-effects multilevel logistic regression was used to
      estimate associations of tobacco vendor and advertisement densities with ever
      tobacco use, current smokeless tobacco use and current tobacco use. RESULTS:
      There were 1741 tobacco vendors and 424 advertisements within 500 m of schools,
      with 221 vendors (13%) and 42 advertisements (10%) located within 100 m. School
      adjacent tobacco vendor density within 100 m was not associated with the tobacco
      use outcomes, but tobacco advertisement density within 100 m was associated with
      all outcomes when comparing highest to lowest density tertiles: ever use (OR:
      2.01; 95% CI 1.00 to 4.07), current use (2.23; 1.16, 4.28) and current smokeless
      tobacco use (2.01; 1.02, 3.98). Tobacco vendor density within 200, 300, 400 and
      500 m of schools was associated with current tobacco use and current smokeless
      tobacco use, but not ever use. CONCLUSIONS: The tobacco sales ban near
      educational institutions could be expanded beyond 100 m. Greater enforcement is
      needed regarding the current bans, particularly because advertisement density
      within 100 m of schools was associated with all students' tobacco use outcomes.

PMID- 23958642
TI  - Modifying roles of glutathione S-transferase polymorphisms on the association
      between cumulative lead exposure and cognitive function.
AB  - BACKGROUND: Glutathione-S-transferase gene (GST) polymorphisms can result in
      variable ability of these enzymes to remove electrophilic substrates. We
      investigated whether the GSTP1 Val105 and GSTM1 deletion polymorphisms modify the
      lead-cognitive function association. METHODS: We used repeated measures analysis
      to compare the association between cumulative lead biomarkers-bone lead measured
      using K-shell X-Ray Fluorescence-and Mini-Mental State Exam (MMSE) score by GST
      variants, adjusted for covariates, among Normative Aging Study participants, a
      Boston-based prospective cohort of men. We had complete data for 698 men
      (providing 1292 observations) for GSTM1 analyses and 595 men (providing 1142
      observations) for GSTP1 analyses. RESULTS: A 15MUg/g higher tibia lead
      concentration (interquartile range of tibia lead) was associated with a 0.24
      point decrement in MMSE score among GSTP1 Val105 variant carriers, which was
      significantly stronger than the association among men with only wild-type alleles
      (p=0.01). The association among GSTP1 Val105 carriers was comparable to that of 3
      years of age in baseline MMSE scores. The association between tibia lead and MMSE
      score appeared progressively steeper in participants with increasingly more GSTP1
      Val105 alleles. A modest association between tibia lead and lower MMSE score was
      seen among participants with the GSTM1 deletion polymorphism. Neither of the
      glutathione S-transferase variants was independently associated with cognitive
      function, nor with lead biomarker measures. The results pertaining to patella
      lead were similar to those observed for tibia lead. CONCLUSION: Our results
      suggest that the GSTP1 Val105 polymorphism confers excess susceptibility to the
      cognitive effects of cumulative lead exposure.

PMID- 23958644
TI  - Countering the demand for, and supply of, illicit tobacco: an assessment of the
      'North of England Tackling Illicit Tobacco for Better Health' Programme.
AB  - BACKGROUND: Illicit tobacco (IT) undermines the effectiveness of tobacco control
      strategies. We assessed the implementation and impact of a new programme designed
      to reduce demand for, as well as supply of, IT, in the north of England, where IT
      was prevalent. METHODS: 'Mixed methods' research was undertaken. Qualitative
      methods included stakeholder interviews (at outset and 1 year later) and
      ethnographic research. Indicators reflecting those supply and demand issues for
      which data were available were identified and monitored, including relevant items
      on two cross-sectional surveys carried out in 2009 and 2011 with over 4000
      individuals from which a social marketing campaign was also developed. IT reports
      to two existing hotlines, promoted through the programme, were assessed. RESULTS:
      Initially, concerns abounded about the different philosophies and ways of working
      of local and national enforcement and health agencies, but these were much
      reduced at follow-up. A protocol was developed which greatly facilitated the flow
      of intelligence about IT supply. A social marketing campaign was developed
      highlighting two messages: IT makes it easier for children to start smoking and
      brings crime into the community, thereby avoiding misleading messages about
      relative harms of illicit and licit tobacco. Public and stakeholder awareness of
      IT increased as did calls to both hotlines. CONCLUSIONS: A partnership of
      agencies, with competing values, was established to tackle IT, a complex public
      health issue and, inter alia, implemented a social marketing campaign using novel
      messages. This improved the flow of intelligence about the supply of IT and
      increased awareness of IT.

PMID- 23958645
TI  - Automated classification of patients with coronary artery disease using grayscale
      features from left ventricle echocardiographic images.
AB  - Coronary Artery Disease (CAD), caused by the buildup of plaque on the inside of
      the coronary arteries, has a high mortality rate. To efficiently detect this
      condition from echocardiography images, with lesser inter-observer variability
      and visual interpretation errors, computer based data mining techniques may be
      exploited. We have developed and presented one such technique in this paper for
      the classification of normal and CAD affected cases. A multitude of grayscale
      features (fractal dimension, entropies based on the higher order spectra,
      features based on image texture and local binary patterns, and wavelet based
      features) were extracted from echocardiography images belonging to a huge
      database of 400 normal cases and 400 CAD patients. Only the features that had
      good discriminating capability were selected using t-test. Several combinations
      of the resultant significant features were used to evaluate many supervised
      classifiers to find the combination that presents a good accuracy. We observed
      that the Gaussian Mixture Model (GMM) classifier trained with a feature subset
      made up of nine significant features presented the highest accuracy, sensitivity,
      specificity, and positive predictive value of 100%. We have also developed a
      novel, highly discriminative HeartIndex, which is a single number that is
      calculated from the combination of the features, in order to objectively classify
      the images from either of the two classes. Such an index allows for an easier
      implementation of the technique for automated CAD detection in the computers in
      hospitals and clinics. 

PMID- 23958646
TI  - Information quality measurement of medical encoding support based on usability.
AB  - Medical encoding support systems for diagnoses and medical procedures are an
      emerging technology that begins to play a key role in billing, reimbursement, and
      health policies decisions. A significant problem to exploit these systems is how
      to measure the appropriateness of any automatically generated list of codes, in
      terms of fitness for use, i.e. their quality. Until now, only information
      retrieval performance measurements have been applied to estimate the accuracy of
      codes lists as quality indicator. Such measurements do not give the value of
      codes lists for practical medical encoding, and cannot be used to globally
      compare the quality of multiple codes lists. This paper defines and validates a
      new encoding information quality measure that addresses the problem of measuring
      medical codes lists quality. It is based on a usability study of how expert
      coders and physicians apply computer-assisted medical encoding. The proposed
      measure, named ADN, evaluates codes Accuracy, Dispersion and Noise, and is
      adapted to the variable length and content of generated codes lists, coping with
      limitations of previous measures. According to the ADN measure, the information
      quality of a codes list is fully represented by a single point, within a suitably
      constrained feature space. Using one scheme, our approach is reliable to measure
      and compare the information quality of hundreds of codes lists, showing their
      practical value for medical encoding. Its pertinence is demonstrated by
      simulation and application to real data corresponding to 502 inpatient stays in
      four clinic departments. Results are compared to the consensus of three expert
      coders who also coded this anonymized database of discharge summaries, and to
      five information retrieval measures. Information quality assessment applying the
      ADN measure showed the degree of encoding-support system variability from one
      clinic department to another, providing a global evaluation of quality
      measurement trends. 

PMID- 23958648
TI  - Basophil activation testing.
AB  - Both the treatment of patients with allergic diseases and the study of allergic
      disease mechanisms depend on a wide variety of assays that in various ways assess
      the presence and function of IgE antibody. The study of allergic diseases could
      benefit from the study of its 2 principle cellular participants, mast cells and
      basophils, but the basophil is more accessible than mast cells for ex vivo
      studies. Its functionality is tested by using 2 predominant methodologies: the
      secretion of mediators of allergic inflammation and the expression of proteins on
      the plasma membrane after stimulation. Each approach has benefits. There are also
      many operational details to consider regardless of which general approach is
      taken, and proper interpretation of the methods requires a good understanding of
      the reagents used and the receptors expressed on basophils and a detailed
      understanding of the factors regulating aggregation of cell-surface IgE.

PMID- 23958647
TI  - IL-4 confers resistance to IL-27-mediated suppression on CD4+ T cells by
      impairing signal transducer and activator of transcription 1 signaling.
AB  - BACKGROUND: TH2 cells play a critical role in the pathogenesis of allergic
      asthma. Established TH2 cells have been shown to resist reprogramming into TH1
      cells. The inherent stability of TH2 cells poses a significant barrier to
      treating allergic diseases. OBJECTIVE: We sought to understand the mechanisms by
      which CD4(+) T cells from asthmatic patients resist the IL-27-mediated
      inhibition. METHODS: We isolated and cultured CD4(+) T cells from both healthy
      subjects and allergic asthmatic patients to test whether IL-27 can inhibit IL-4
      production by the cultured CD4(+) T cells using ELISA. Culturing conditions that
      resulted in resistance to IL-27 were determined by using both murine and human
      CD4(+) T-cell culture systems. Signal transducer and activator of transcription
      (STAT) 1 phosphorylation was analyzed by means of Western blotting and flow
      cytometry. Suppressor of cytokine signaling (Socs) mRNA expression was measured
      by using quantitative PCR. The small interfering RNA method was used to knockdown
      the expression of Socs3 mRNA. RESULTS: We demonstrated that CD4(+) T cells from
      asthmatic patients resisted the suppression of IL-4 production mediated by IL-27.
      We observed that repeated exposure to TH2-inducing conditions rendered healthy
      human CD4(+) T cells resistant to IL-27-mediated inhibition. Using an in vitro
      murine culture system, we further demonstrated that repeated or higher doses of
      IL-4 stimulation, but not IL-2 stimulation, upregulated Socs3 mRNA expression and
      impaired IL-27-induced STAT1 phosphorylation. The knockdown of Socs3 mRNA
      expression restored IL-27-induced STAT1 phosphorylation and IL-27-mediated
      inhibition of IL-4 production. CONCLUSIONS: Our findings demonstrate that
      differentiated TH2 cells can resist IL-27-induced reprogramming toward TH1 cells
      by downregulating STAT1 phosphorylation and likely explain why the CD4(+) T cells
      of asthmatic patients are resistant to IL-27-mediated inhibition.

PMID- 23958650
TI  - Phenotypic screens targeting neurodegenerative diseases.
AB  - Neurodegenerative diseases affect millions of people worldwide, and the
      incidences increase as the population ages. Disease-modifying therapy that
      prevents or slows disease progression is still lacking, making neurodegenerative
      diseases an area of high unmet medical need. Target-based drug discovery for
      disease-modifying agents has been ongoing for many years, without much success
      due to incomplete understanding of the molecular mechanisms underlying
      neurodegeneration. Phenotypic screening, starting with a disease-relevant
      phenotype to screen for compounds that change the outcome of biological pathways
      rather than activities at certain specific targets, offers an alternative
      approach to find small molecules or targets that modulate the key characteristics
      of neurodegeneration. Phenotypic screens that focus on amelioration of disease
      specific toxins, protection of neurons from degeneration, or promotion of
      neuroregeneration could be potential fertile grounds for discovering therapeutic
      agents for neurodegenerative diseases. In this review, we will summarize the
      progress of compound screening using these phenotypic-based strategies for this
      area, with a highlight on unique considerations for disease models, assays, and
      screening methodologies. We will further provide our perspectives on how best to
      use phenotypic screening to develop drug leads for neurodegenerative diseases. 

PMID- 23958649
TI  - Adherence to criteria for transvaginal ultrasound imaging and measurement of
      cervical length.
AB  - OBJECTIVE: Adherence to published criteria for transvaginal imaging and
      measurement of cervical length is uncertain. We sought to assess adherence by
      evaluating images submitted to certify research sonographers for participation in
      a clinical trial. STUDY DESIGN: We reviewed qualifying test results of
      sonographers seeking certification to image and measure cervical length in a
      clinical trial. Participating sonographers were required to access training
      materials and submit 15 images, 3 each from 5 pregnant women not enrolled in the
      trial. One of 2 sonologists reviewed all qualifying images. We recorded the
      proportion of images that did not meet standard criteria (excess compression,
      landmarks not seen, improper image size, or full maternal bladder) and the
      proportion in which the cervical length was measured incorrectly. Failure for a
      given patient was defined as >1 unacceptable image, or >2 acceptable images with
      incorrect caliper placement or erroneous choice of the "shortest best" cervical
      length. Certification required satisfactory images and cervical length
      measurement from >=4 patients. RESULTS: A total of 327 sonographers submitted
      4905 images. A total of 271 sonographers (83%) were certified on the first, 41
      (13%) on the second, and 2 (0.6%) on the third submission. Thirteen never
      achieved certification. Of 314 who passed, 196 submitted 15 acceptable images
      that were appropriately measured for all 5 women. There were 1277 deficient
      images: 493 were acceptable but incorrectly measured images from sonographers who
      passed certification because mismeasurement occurred no more than twice. Of 784
      deficient images submitted by sonographers who failed the certification, 471 were
      rejected because of improper measurement (caliper placement and/or failure to
      identify the shortest best image), and 313 because of failure to obtain a
      satisfactory image (excessive compression, required landmarks not visible,
      incorrect image size, brief examination, and/or full maternal bladder).
      CONCLUSION: Although 83% of sonographers were certified on their first
      submission, >1 in 4 ultrasound images submitted did not meet published quality
      criteria. Increased attention to standardized education and credentials is
      warranted for persons who perform ultrasound examinations of the cervix in
      pregnancy.

PMID- 23958651
TI  - Anti-obesity phenotypic screening looking to increase OBR cell surface
      expression.
AB  - The leptin receptor, OBR, is involved in the regulation of whole-body energy
      homeostasis. Most obese people are resistant to leptin and do not respond to the
      hormone. The prevention and reversal of leptin resistance is one of the major
      current goals of obesity research. We showed previously that increased OBR cell
      surface expression concomitantly increases cellular leptin signaling and prevents
      obesity development in mice. Improvement of OBR cell surface expression can thus
      be considered as an interesting anti-obesity therapeutic strategy. To identify
      compounds that increase the surface expression of OBR, we developed a cell-based,
      phenotypic assay to perform a high-content screen (HCS) against a library of
      50,000 chemical compounds. We identified 67 compounds that increased OBR cell
      surface expression with AC50 values in the low micromolar range and no effect on
      total OBR expression and cellular toxicity. Compounds were classified into 16
      chemical clusters, of which 4 potentiated leptin-promoted signaling through the
      JAK2/STAT3 pathway. In conclusion, development of a robust phenotypic screening
      approach resulted in the discovery of four new scaffolds that demonstrate the
      desired biological activity and could constitute an original therapeutic solution
      against obesity and associated disorders. 

PMID- 23958652
TI  - Association of the + 45T>G adiponectin gene polymorphism with insulin resistance
      in non-diabetic Saudi women.
AB  - BACKGROUND: The human adiponectin gene variations are associated with obesity,
      insulin resistance, and diabetes. However, these associations have not been fully
      examined in a non-diabetic population in Saudi Arabia. We aimed to investigate
      the association of 45T>G single nucleotide polymorphism (SNP) in the adiponectin
      gene with total adiponectin levels, insulin resistance (IR), fasting blood
      glucose (FBG) and other markers of obesity in non-diabetic Saudi females.
      METHODS: One hundred non diabetic Saudi females were enrolled in this study. They
      were further divided according to their body mass index (BMI) into two groups.
      Group I, 46 non diabetic subjects with normal body weight and group II, 54
      overweight and obese females. Adiponectin 45T/G polymorphism was detected by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
      Serum adiponectin was measured by ELISA. RESULTS: Obese women exhibited a higher
      distribution of TG/GG genotype compared with non-obese women. SNP +45T>G
      genotypes were associated with higher FBG, insulin levels and HOMA-IR with lower
      total adiponectin levels in obese Saudi women. Otherwise the all estimated
      variables revealed non-significant differences among the non-obese genotypes. The
      observed differences in insulin resistance markers were very significant among
      women with a higher body weight but not among normal body weight women, thus
      suggesting that SNP +45T>G effects on insulin sensitivity may depend upon body
      weight and body fat status. CONCLUSION: SNP +45T>G of adiponectin gene has a
      significant role in the development of insulin resistance in Saudi women possibly
      through an interaction with increase body weight and hypoadiponectinemia.

PMID- 23958653
TI  - Genetic analysis of TMPRSS3 gene in the Korean population with autosomal
      recessive nonsyndromic hearing loss.
AB  - The TMPRSS3 gene (DFNB8/10), which encodes a transmembrane serine protease, is a
      common hearing loss gene in several populations. Accurate functions of TMPRSS3 in
      the hearing pathway are still unknown, but TMPRSS3 has been reported to play a
      crucial role in inner ear development or maintenance. To date, 16 pathogenic
      mutations have been identified in many countries, but no mutational studies of
      the TMPRSS3 gene have been conducted in the Korean hearing loss population. In
      this study, we performed genetic analysis of TMPRSS3 in 40 unrelated Korean
      patients with autosomal recessive hearing loss to identify the aspect and
      frequency of TMPRSS3 gene mutations in the Korean population. A total of 22
      variations were detected, including a novel variant (p.V291L) and a previously
      reported pathogenic mutation (p.A306T). The p.A306T mutation which has been
      detected in only compound heterozygous state in previous studies was identified
      in homozygous state for the first time in this study. Moreover, the clinical
      evaluation identified bilateral dilated vestibules in the patient with p.A306T
      mutation, and it suggested that p.A306T mutation of the TMPRSS3 gene might be
      associated with vestibular anomalies. In conclusion, this study investigated that
      only 2.5% of patients with autosomal recessive hearing loss were related to
      TMPRSS3 mutations suggesting low prevalence of TMPRSS3 gene in Korean hearing
      loss population. Also, it will provide the information of genotype-phenotype
      correlation to understand definite role of TMPRSS3 in the auditory system.

PMID- 23958654
TI  - Dehydration mediated microRNA response in the African clawed frog Xenopus laevis.
AB  - Exposure to various environmental stresses induces metabolic rate depression in
      many animal species, an adaptation that conserves energy until the environment is
      again conducive to normal life. The African clawed frog, Xenopus laevis, is
      periodically subjected to arid summers in South Africa, and utilizes entry into
      the hypometabolic state of estivation as a mechanism of long term survival.
      During estivation, frogs must typically deal with substantial dehydration as
      their ponds dry out and X. laevis can endure >30% loss of its body water. We
      hypothesize that microRNAs play a vital role in establishing a reversible
      hypometabolic state and responding to dehydration stress that is associated with
      amphibian estivation. The present study analyzes the effects of whole body
      dehydration on microRNA expression in three tissues of X. laevis. Compared to
      controls, levels of miR-1, miR-125b, and miR-16-1 decreased to 37+/-6, 64+/-8,
      and 80+/-4% of control levels during dehydration in liver. By contrast, miR-210,
      miR-34a and miR-21 were significantly elevated by 3.05+/-0.45, 2.11+/-0.08, and
      1.36+/-0.05-fold, respectively, in the liver. In kidney tissue, miR-29b, miR-21,
      and miR-203 were elevated by 1.40+/-0.09, 1.31+/-0.05, and 2.17+/-0.31-fold,
      respectively, in response to dehydration whereas miR-203 and miR-34a were
      elevated in ventral skin by 1.35+/-0.05 and 1.74+/-0.12-fold, respectively.
      Bioinformatic analysis of the differentially expressed microRNAs suggests that
      these are mainly involved in two processes: (1) expression of solute carrier
      proteins, and (2) regulation of mitogen-activated protein kinase signaling. This
      study is the first report that shows a tissue specific mode of microRNA
      expression during amphibian dehydration, providing evidence for microRNAs as
      crucial regulators of metabolic depression. 

PMID- 23958655
TI  - Expression analysis of rice VQ genes in response to biotic and abiotic stresses.
AB  - WRKY transcription factors are encoded by a large gene superfamily with a broad
      range of roles in plants. Proteins containing a short VQ (FxxxVQxLTG) motif have
      been recently shown to interact with WRKY transcription factors, implying that
      AtVQ proteins are important in the plant defense responses in Arabidopsis, either
      as positive or negative cofactors of WRKY transcription factors. Thirty-nine
      Oryza sativa genes containing the VQ motif (OsVQs) were identified and the genome
      structures of OsVQ proteins were characterized through genome-wide analysis in
      rice. Also, phylogenetic tree analysis was performed with the VQ domain of
      Arabidopsis and rice. The expression patterns of these OsVQ genes in plants under
      several stress treatments were assessed, specifically, following infection with
      the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo), treatment with
      abscisic acid (ABA), or exposure to drought. The cellular localization of a few
      OsVQ proteins was examined using rice protoplast system. Based on our results, we
      suggest that OsVQ proteins function as important co-regulators during the plant
      defense response to biotic and abiotic stresses. 

PMID- 23958656
TI  - Z curve theory-based analysis of the dynamic nature of nucleosome positioning in
      Saccharomyces cerevisiae.
AB  - Nucleosome is the elementary structural unit of eukaryotic chromatin. Instability
      of nucleosome positioning plays critical roles in chromatin remodeling in
      differentiation and disease. In this study, we investigated nucleosome dynamics
      in the Saccharomyces cerevisiae genome using a geometric model based on Z curve
      theory. We identified 52,941 stable nucleosomes and 7607 dynamic nucleosomes,
      compiling them into a genome-wide nucleosome dynamic positioning map and
      constructing a user-friendly visualization platform
      (http://bioinfo.hrbmu.edu.cn/nucleosome). Our approach achieved a sensitivity of
      90.31% and a specificity of 87.76% for S. cerevisiae. Analysis revealed
      transcription factor binding sites (TFBSs) were enriched in linkers. And among
      the sparse nucleosomes around TFBSs, dynamic nucleosomes were slightly preferred.
      Gene Ontology (GO) enrichment analysis indicated that stable and dynamic
      nucleosomes were enriched on genes involved in different biological processes and
      functions. This study provides an approach for comprehending chromatin remodeling
      and transcriptional regulation of genes.

PMID- 23958657
TI  - Deletion of the 5'exons of COL4A6 is not needed for the development of diffuse
      leiomyomatosis in patients with Alport syndrome.
AB  - BACKGROUND: Alport syndrome (AS), a hereditary type IV collagen nephropathy, is a
      major cause of end-stage renal disease in young people. About 85% of the cases
      are X-linked (ATS), due to mutations in the COL4A5 gene. Rarely, families have a
      contiguous gene deletion comprising at least exon 1 of COL4A5 and the first exons
      of COL4A6, associated with the development of diffuse leiomyomatosis (ATS-DL). We
      report three novel deletions identified in families with AS, one of which
      challenges the current concepts on genotype-phenotype correlations of ATS/ATS-DL.
      METHODS: In the setting of a multicentric study aiming to describe the genetic
      epidemiology and molecular pathology of AS in Portugal, three novel COL4A5
      deletions were identified in two families with x-linked Alport syndrome (ATS) and
      in one family with ATS-DL. These mutations were initially detected by PCR and
      Multiplex Ligation-dependent Probe Amplification, and further mapped by high
      resolution X chromosome-specific oligo-array and PCR. RESULTS: In the ATS-DL
      family, a COL4A5 deletion spanning exons 2 through 51, extending distally beyond
      COL4A5 but proximally not into COL4A6, segregated with the disease phenotype. A
      COL4A5 deletion encompassing exons 2 through 29 was identified in one of the ATS
      families. In the second ATS family, a deletion of exon 13 of COL4A5 through exon
      3 of COL4A6 was detected. CONCLUSIONS: These observations suggest that deletion
      of the 5' exons of COL4A6 and of the common promoter of the COL4A5 and COL4A6
      genes is not essential for the development of leiomyomatosis in patients with
      ATS, and that COL4A5_COL4A6 deletions extending into COL4A6 exon 3 may not result
      in ATS-DL.

PMID- 23958658
TI  - Evidence of natural transmission of group A rotavirus between domestic pigs and
      wild boars (Sus scrofa) in Japan.
AB  - Group A rotaviruses (RVAs) are a major cause of acute dehydrating diarrhea in
      infants and young animals worldwide. RVAs have also been detected in several wild
      and zoo animals, indicating wide susceptibility of wild animals. However, the
      role of wild animals in the infection cycle of RVAs is unclear. Wild boars are
      indigenous in many countries in the world. Japanese wild boars (Sus scrofa
      leucomystax) have been migrating close to human habitats in Japan, indicating the
      possibility of natural transmission between domestic animals or humans and wild
      boars. We investigated infection of RVAs in wild boars in Japan to identify types
      of RVAs infecting wild animals. We obtained stool samples from 90 wild boars and
      detected a VP4 gene of RVAs by RT-semi-nested PCR. RVAs were detected in samples
      from four of the 90 wild boars. Nucleotide analyses of VP7 and VP4 genes revealed
      that the four strains belong to G9P[23], G4P[23], G9P[13] and G4P[6], suggesting
      a relation to porcine and human RVAs. We therefore characterized RVAs circulating
      among domestic pigs living in the same area as the wild boars. We collected stool
      samples from 82 domestic pigs. RVAs were detected in samples from 49 of the 82
      domestic pigs. Phylogenetic and similarity analyses provided evidence for natural
      transmission between domestic pigs and wild boars. The results also suggested
      that natural reassortment events occurred before or after transmission between
      domestic pigs and wild boars. Our findings indicate the possibility that RVAs
      circulate among wild animals, humans and domestic animals in nature. 

PMID- 23958663
TI  - Neuroscience thinks big (and collaboratively).
AB  - Despite cash-strapped times for research, several ambitious collaborative
      neuroscience projects have attracted large amounts of funding and media
      attention. In Europe, the Human Brain Project aims to develop a large-scale
      computer simulation of the brain, whereas in the United States, the Brain
      Activity Map is working towards establishing a functional connectome of the
      entire brain, and the Allen Institute for Brain Science has embarked upon a 10
      year project to understand the mouse visual cortex (the MindScope project). US
      President Barack Obama's announcement of the BRAIN Initiative (Brain Research
      through Advancing Innovative Neurotechnologies Initiative) in April 2013
      highlights the political commitment to neuroscience and is expected to further
      foster interdisciplinary collaborations, accelerate the development of new
      technologies and thus fuel much needed medical advances. In this Viewpoint
      article, five prominent neuroscientists explain the aims of the projects and how
      they are addressing some of the questions (and criticisms) that have arisen.

PMID- 23958666
TI  - Making a difference through grassroots legislative action.

PMID- 23958667
TI  - Recognizing and managing acute anaphylaxis.

PMID- 23958670
TI  - Arthrocentesis: the latest on joint pain relief.
AB  - Arthrocentesis is a procedure in the diagnostic workup and treatment of joint
      pain that has few complications. Analysis of joint fluid yields important
      treatment data. Corticosteroid and local anesthetic injections provide longer
      pain relief.

PMID- 23958671
TI  - IUDs: beyond the basics.
AB  - This article reviews the changes in patient selection for intrauterine devices
      (IUDs) and evidence-based practices regarding counseling and management of common
      IUD issues. Where evidence-based research is lacking, expert opinion and common
      standards of practice are reviewed, and current clinical resources are
      identified.

PMID- 23958672
TI  - Performing oral health screenings on children.
AB  - This article describes ways to elicit the cooperation of a young patient while
      limiting fear and/or alarm, provides steps for performing a complete oral exam to
      evaluate the oral health of a child, and discusses reimbursement for the
      application of fluoride varnish.

PMID- 23958674
TI  - Loneliness and quality of life in chronically ill rural older adults.
AB  - BACKGROUND: Loneliness is a contributing factor to various health problems in
      older adults, including complex chronic illness, functional decline, and
      increased risk of mortality. OBJECTIVES: A pilot study was conducted to learn
      more about the prevalence of loneliness in rural older adults with chronic
      illness and how it affects their quality of life. The purposes of the data
      analysis reported here were twofold: to describe loneliness, chronic illness
      diagnoses, chronic illness control measures, prescription medication use, and
      quality of life in a sample of rural older adults; and to examine the
      relationships among these elements. METHODS: A convenience sample of 60
      chronically ill older adults who were community dwelling and living in Appalachia
      was assessed during face-to-face interviews for loneliness and quality of life,
      using the University of California, Los Angeles (UCLA) Loneliness Scale (version
      3) and the CASP-12 quality of life scale. Chronic illness diagnoses, chronic
      illness control measures, and medication use data were collected through review
      of participants' electronic medical records. RESULTS: Overall mean loneliness
      scores indicated significant loneliness. Participants with a mood disorder such
      as anxiety or depression had the highest mean loneliness scores, followed by
      those with lung disease and those with heart disease. Furthermore, participants
      with mood disorders, lung disease, or heart disease had significantly higher
      loneliness scores than those without these conditions. Loneliness was
      significantly related to total number of chronic illnesses and use of
      benzodiazepines. Use of benzodiazepines, diuretics, nitrates, and bronchodilators
      were each associated with a lower quality of life. CONCLUSIONS: Nurses should
      assess for loneliness as part of their comprehensive assessment of patients with
      chronic illness. Further research is needed to design and test interventions for
      loneliness.

PMID- 23958675
TI  - Care of pregnant women in the criminal justice system.
AB  - Current practices in the treatment and transfer of pregnant inmates in this
      country may negatively affect maternal and fetal health or well-being. Some
      violate federal or state laws; others conflict with standards of obstetric care
      and are widely considered unethical or inhumane. This article discusses these
      practices; their legal status; and implications for nursing practice, policy, and
      research.

PMID- 23958676
TI  - Surgery, wound healing, and metastasis: recent insights and clinical
      implications.
AB  - BACKGROUND: Surgery-induced acceleration of tumour growth has been observed since
      several centuries. METHODS: We reviewed recent insights from in vitro data,
      animal experimentation, and clinical studies on how surgery-induced wound healing
      or resection of a primary cancer influences the tumour-host ecosystem in patients
      harbouring minimal residual or metastatic disease. RESULTS: Most of the growth
      factors, chemokines, and cytokines orchestrating surgical wound healing promote
      tumour growth, invasion, or angiogenesis. In addition, resection of a primary
      tumour may accelerate synchronous metastatic growth. In the clinical setting,
      indirect evidence supports the relevance of the above findings. Randomized
      clinical trials are underway comparing resection versus observation in metastatic
      breast and colon cancer with asymptomatic primary tumours. CONCLUSIONS: In depth
      knowledge of how surgical intervention alters the tumour-host-metastasis
      communicating ecosystems could have important implications for clinical decision
      making in patients with synchronous metastatic disease and for the design and
      timing of multimodality treatment strategies.

PMID- 23958677
TI  - Protein S: A multifunctional anticoagulant vitamin K-dependent protein at the
      crossroads of coagulation, inflammation, angiogenesis, and cancer.
AB  - Since its discovery in 1970, protein S (PS) has emerged as a key vitamin K
      dependent natural anticoagulant protein at the crossroads of multiple biological
      processes, including coagulation, apoptosis, atherosclerosis,
      angiogenesis/vasculogenesis, and cancer progression. Following the binding to a
      unique family of protein tyrosine kinase receptors referred to as Tyro-3, Axl and
      Mer (TAM) receptors, PS can lead to regulation of coagulation, phagocytosis of
      apoptotic cells, cell survival, activation of innate immunity, vessel integrity
      and angiogenesis, and local invasion and metastasis. Because of these dynamics
      and multiple functions of PS, which are largely lost following invalidation of
      the mouse PROS1 gene, this molecule is currently intensively studied in
      biomedical research. The purpose of this review is to provide a brief chronicle
      of the discovery and current understanding of the mechanisms of PS signaling, and
      how PS and their signaling partners regulate various cellular functions, with a
      particular focus on TAM receptors.

PMID- 23958678
TI  - Influence of strain-specific parameters on hydrothermal liquefaction of
      microalgae.
AB  - Algae are an interesting feedstock for producing biofuel via hydrothermal
      liquefaction (HTL), due to their high water content. In this study, algae
      slurries (5-7 wt% daf) from different species were liquefied at 250 and 375 
      degrees C in batch autoclaves during 5 min. The aim was to analyze the influence
      of strain-specific parameters (cell structure, biochemical composition and growth
      environment) on the HTL process. Results show big variations in the biocrude oil
      yield within species at 250  degrees C (from 17.6 to 44.8 wt%). At 375  degrees
      C, these differences become less significant (from 45.6 to 58.1 wt%). An
      appropriate characterization of feedstock appeared to be critical to interpret
      the results. If a high conversion of microalgae-to-biocrude is pursued, near
      critical conditions are required, with Scenedesmus almeriensis (freshwater) and
      Nannochloropsis gaditana (marine) leading to the biocrude oils with lower
      nitrogen content from each growth environment.

PMID- 23958679
TI  - Preparation and upgrading of hydrocarbon oil from deoxy-liquefaction of oil crop.
AB  - Deoxy-liquefaction of cotton seed in husk was carried out to produce hydrocarbon
      oil at different temperatures (400-500  degrees C). Results indicated that at 450
      degrees C, the obtained oil had a maximum alkanes value of 49.58% with a low
      oxygen content (1.4%) resulting in the increase of HHV (43.8 MJ kg(-1)), whereas
      the oil contained considerable nitrogenous compounds. In the presence of gamma
      Al2O3-CuO catalyst, at 450  degrees C nitrogen content in the oil dropped 20%,
      exhibiting the activity of catalysis for denitrification, when the content of
      alkanes rose to 54.91%; by vacuum distillation, the oil was then separated into
      light/heavy fractions which showed that they both possessed rich carbon and
      hydrogen with low oxygen contents. The light fractions were much the same as that
      of gasoline, while the heavy fractions were close to diesel, which laid the
      foundation of further treatment and applications.

PMID- 23958680
TI  - Reducing non-productive adsorption of cellulase and enhancing enzymatic
      hydrolysis of lignocelluloses by noncovalent modification of lignin with
      lignosulfonate.
AB  - Four fractions of one commercial sodium lignosulfonate (SXP) with different
      molecular weight (MW) and anionic polymers were studied to reduce non-productive
      adsorption of cellulase on bound lignin in a lignocellulosic substrate. SXP with
      higher MW had stronger blocking effect on non-productive adsorption of a
      commercial Trichoderma reesi cellulase cocktail (CTec2) on lignin measured by
      quartz crystal microgravimetry with dissipation monitoring. Linear anionic
      aromatic polymers have strong blocking effect, but they would also reduce CTec2
      adsorption on cellulose to decrease the enzymatic activity. The copolymer of
      lignin and polyethylene glycol (AL-PEG1000) has strong enhancement in enzymatic
      hydrolysis of lignocelluloses, because it not only improves the cellulase
      activity to cellulose, but also blocks the non-productive cellulase adsorption on
      lignin. Apart from improving the cellulase activity to cellulose, the
      enhancements of enzymatic hydrolysis of lignocellulose by adding AL-PEG1000 and
      SXPs are the result of the decreased cellulase non-productive adsorption on
      lignin.

PMID- 23958681
TI  - Investigation of thermodynamic parameters in the pyrolysis conversion of biomass
      and manure to biochars using thermogravimetric analysis.
AB  - The thermodynamic parameters of the conversion of two companion pair materials,
      i.e., rice straw vs dairy manure, and rice bran vs chicken manure, to biochars
      were characterized by thermogravimetric analysis. The overall changes of
      activation energy (Ea) were well described by the Flynn-Wall method. The Ea
      values increased steeply from about 120 to 180 kJ/mol at the mass conversion
      (alpha) at 0.2-0.4, followed by a relatively steady change at 0.4<alpha<0.65,
      thereafter showed a quick increase at alpha>0.65. The higher contents of minerals
      in manures resulted in the larger Ea. The individual conversion of hemicellulose,
      cellulose and lignin in the feedstocks was identified and their thermodynamic
      parameters (DeltaH degrees , DeltaG degrees  and DeltaS degrees ) were
      calculated. The yields of biochars calculated from TG curve were compared with
      the determined yields of biochars using muffle pyrolysis. Along with Fourier
      transform infrared spectra data, the distinct decompositions of biomasses and
      manures were evaluated.

PMID- 23958682
TI  - Two-stage anaerobic membrane bioreactor for the treatment of sugarcane vinasse:
      assessment on biological activity and filtration performance.
AB  - A two-stage submerged anaerobic membrane bioreactor (2-SAnMBR) was designed for
      the treatment of sugarcane vinasse. For start-up, the flow rate was reduced
      whenever VFA levels reached critical levels in the methanogenic reactor. After
      acclimation, the system was operated under a continuous flow. Separation of the
      stages was observed during the entire period of operation. VFA, COD and DOC
      levels of raw effluent, acidified effluent and permeate averaged 2141, 3525 and
      61 mg VFA L(-1) (as acetic acid), 15727, 11512 and 488 mg COD L(-1), and, 3544,
      3533 and 178 mg DOC L(-1), respectively. Overall COD and DOC removal efficiencies
      of 96.9+/-0.7% and 95.0+/-1.1%, respectively, were reached. Methane content of
      the biogas from the acidogenic and methanogenic reactors ranged 0.1-4.6% and 60.1
      70.1%, respectively. Removable fouling strongly affected filtration performance
      and cake layer formation accounted for most of filtration resistance. Membrane
      resistance was related to presence of protein-like substances and carbohydrates.

PMID- 23958683
TI  - Modulation of antitumour immune responses by intratumoural Stat1 expression.
AB  - Signal transducer and activator of transcription 1 (Stat1) mediates anti-viral
      responses and cytokine-driven anti-proliferative, apoptotic and immunomodulatory
      activities. As de-regulated Stat1 function can affect tumour progression we
      sought to elucidate the effects of tumour cell-intrinsic Stat1 expression on
      immunosurveillance. Knockout of Stat1 enhanced the development of sarcomas
      induced by the chemical carcinogen 3-methylcholanthrene (MCA). Growth of
      transplanted MCA-induced Stat1-/- sarcomas was suppressed in wild-type mice
      compared to growth in Stat1-/- and immunocompromised recipients. Co-depletion of
      NK and CD8+ T cells from wild-type mice facilitated Stat1-deficient tumour growth
      whereas depletion of CD4+ T cells and CD8+ T cells did not. In vitro and in vivo
      analysis of the tumours implicated a role for NK cell-mediated, perforin
      dependent killing of Stat1-deficient tumours. Interestingly, restoration of Stat1
      expression in Stat1-/- tumours resulted in diminished involvement of NK cells and
      increased contribution of CD8+ T cells in anti-tumour responses. Therefore, Stat1
      expression within tumour cells modulated anti-tumour immune responses by altering
      the dominant immune effector cell involvement from NK cells to CD8+ T cells in
      the absence or presence of Stat1 respectively.

PMID- 23958684
TI  - Modification with hemeproteins increases the diffusive movement of nanorods in
      dilute hydrogen peroxide solutions.
AB  - Nanorods were decorated with different hemeproteins that are able to convert
      hydrogen peroxide. When dispersed into hydrogen peroxide solutions, most of these
      nanorods are characterized by diffusion coefficients which increase with the
      concentration of hydrogen peroxide. Such a behaviour does not characterize
      unmodified nanorods. 

PMID- 23958685
TI  - Synthesis, tailoring and characterization of silica nanoparticles containing a
      highly stable ruthenium complex.
AB  - This paper describes the synthesis and characterization of sol-gel silica
      nanoparticles (NPs) derived from tetraethoxysilane (TEOS) and from
      tetraethoxysilane and methyltriethoxysilane (TEOS-MTEOS) in which is
      encapsulated, an in-house synthesized, stable oxygen-sensitive ruthenium complex,
      ruthenium (II) (bis-2,2-bipyridyl)-2(4-carboxylphenyl) imidazo[4,5
      f][1,10]phenanthroline. These NPs were characterized using dynamic light
      scattering, transmission electron microscopy, scanning electron microscopy,
      Fourier transform infrared spectroscopy and Brunauer-Emmett-Teller analysis. The
      spherical, stable and monodispersed NPs have been prepared using the Stober
      method. It was found that the addition of prehydrolyzed MTEOS-based sol prepared
      in an acidic environment to the reaction mixture containing TEOS NPs synthesized
      for 6 h produced material with increased porosity when compared to pure silica
      NPs. Oxygen sensitivity, stability, photobleaching and leaching have been
      characterized. The hybrid NPs exhibit enhanced O2 sensitivity but a high degree
      of leaching when compared to pure silica NPs, which have minimum O2 sensitivity
      and no leaching.

PMID- 23958686
TI  - Claiming positive results from negative trials: a cause for concern in randomized
      controlled trial research.

PMID- 23958687
TI  - Epidemiological, clinical and viral characteristics of fatal cases of human avian
      influenza A (H7N9) virus in Zhejiang Province, China.
AB  - BACKGROUND: The high mortality of avian influenza H7N9 in humans is a cause of
      great concern in China. METHODS: We compared epidemiological, clinical and viral
      features of H7N9 influenza of 10 fatal cases and 30 survivors. RESULTS:
      Increasing age (p = 0.021), smoking (p = 0.04), underlying medical background (p
      = 0.05) and chronic drug use (p = 0.042) had a strong relationship with death due
      to H7N9 infection. Serological inflammatory markers were higher in fatal cases
      compared to survivors. Acute respiratory distress syndrome (100%), respiratory
      failure (100%), co-infection with bacteria (60%), shock (50%) and congestive
      heart failure (50%) were the most common complications observed in fatal cases.
      The median time from onset of symptoms to antiviral therapy was 4.6 and 7.4 days
      in those who survived and those who died, respectively (p = 0.04). Viral HA, NA
      and MP nucleotide sequences of isolates from both study groups exhibited high
      molecular genetic homology. CONCLUSIONS: Age along with a history of smoking,
      chronic lung disease, immuno-suppressive disorders, chronic drug use and delayed
      Oseltamivir treatment are risk factors which might contribute to fatal outcome in
      human H7N9 infection.

PMID- 23958688
TI  - Segmented flow and curtain flow chromatography: overcoming the wall effect and
      heterogeneous bed structures.
AB  - The variation in mobile phase velocity as a function of the column radius has
      been shown to be a major limitation in the efficiency of HPLC columns. One
      contributing factor to the variability in the flow velocity stems from the
      heterogeneity in the radial packing density, leading to what has been described
      as the 'wall-effect'. The wall-effect generates parabolic-type elution profiles,
      which dilutes the sample and creates tailing bands. In this communication a new
      column technology is discussed that has been designed to overcome the wall
      effect, minimising the limitations associated with packing heterogeneity. This
      technology has been referred to as active flow technology and consists of two
      types of column designs, parallel segmented flow and curtain flow. In both these
      column designs sample that elutes through the column in the radial central region
      of the bed is separated from the flow that elutes along the wall region. Hence,
      the sample that elutes through the most efficiently packed region of the bed is
      collected to the detector. As a consequence more theoretical plates are obtained,
      and sensitivity is increased since the sample is not diluted by the diffuse tail.
      Sensitivity is enhanced further in the curtain flow design. The benefits of these
      new columns are discussed. 

PMID- 23958689
TI  - Modeling the chiral resolution ability of highly sulfated beta-cyclodextrin for
      basic compounds in electrokinetic chromatography.
AB  - Despite the fact that extensive research in the field of enantioseparations by
      capillary electrophoresis has been carried out, it is difficult to predict
      whether a concrete chiral selector would be useful for the separation of a
      racemic compound. Hence, several experimental effort is necessary to test the
      abilities of individual chiral selectors, usually by trial and error procedures.
      Thus, the enantioseparation of a new racemate becomes a time- and money-consuming
      task. In this work, the ability of highly sulfated beta-cyclodextrin (HS-beta-CD)
      as chiral selector in electrokinetic chromatography (EKC) is modeled for the
      first time, using exclusively directly-available structural data of forty
      compounds (structurally unrelated basic drugs and pesticides). A discriminant
      partial least squares (PLS)-based quantitative structure-property relationship
      (QSPR) approach is simplified, resulting in a consistent, predictive and
      descriptive model. It is converted into an explicit equation able to predict the
      enantioresolution level (Rs) of new compounds, from four structure properties
      available in an on-line open database: logarithm of octanol-water partition
      coefficient estimated at pH 7.4 (lgD), polar surface area (PSA), number of
      hydrogen bond donors (HBD) and acceptors (HBA). For the cases in which the model
      predicts good Rs only in concrete experimental conditions, a Box-Behnken
      experimental design is proposed for the fast PLS-based optimization of the most
      influential experimental variables: cyclodextrin concentration, temperature and
      pH.

PMID- 23958690
TI  - Properties of columns with several pyridinium and imidazolium ionic liquid
      stationary phases.
AB  - Recent advances in the development of new liquid phases (ILs) made it possible to
      use some classes of ILs as polar stationary liquid phases (SLP). In our days only
      alkylimidazolium- and alkylphosphonium-based ILs are widely used as polar SLP. In
      present work some other types of ILs - pyridinium and cyanopropyl/hydroxypropyl
      imidazolium were investigated as SLP. Columns with efficiencies 2000-2500
      plates/m by high-pressure static method were prepared. Polarity and selectivity
      of these phases were measured. Selectivity was described in terms of
      intermolecular interactions by using Abraham solvatation parameter model. The set
      of the regularities between cation structure of ionic liquid and selectivity has
      been shown. The number and position of methyl groups in ionic liquid pyridinium
      ring were shown to have the sufficient influence on all type of molecular
      interactions. Finally the resolutions of test mixture for the several ionic
      liquid SLP were obtained. For columns with some ionic liquids the dependencies of
      the height equivalent to a theoretical plate (HETP) and sample loading capacity
      were obtained and compared with the conventional phases. It was found that the
      optimal efficiency for the IL columns is attained at lower carrier gas velocities
      in comparison with traditional phases. Nevetheless sample loading capacity of IL
      phases is comparable to those of conventional GC phases. 

PMID- 23958691
TI  - Ultra-high-performance liquid chromatography-tandem mass spectrometry measurement
      of climbazole deposition from hair care products onto artificial skin and human
      scalp.
AB  - A sensitive and specific ultra-high-performance liquid chromatography-tandem mass
      spectrometry (UHPLC-MS/MS) method was developed and validated for the measurement
      of climbazole deposition from hair care products onto artificial skin and human
      scalp. Deuterated climbazole was used as the internal standard. Atmospheric
      pressure chemical ionization (APCI) in positive mode was applied for the
      detection of climbazole. For quantification, multiple reaction monitoring (MRM)
      transition 293.0>69.0 was monitored for climbazole, and MRM transition
      296.0>225.1 for the deuterated climbazole. The linear range ran from 4 to 2000 ng
      mL(-1). The limit of detection (LOD) and the limit of quantification (LOQ) were 1
      ng mL(-1) and 4 ng mL(-1), respectively, which enabled quantification of
      climbazole on artificial skin and human scalp at ppb level (corresponding to 16
      ng cm(-2)). For the sampling of climbazole from human scalp the buffer scrub
      method using a surfactant-modified phosphate buffered saline (PBS) solution was
      selected based on a performance comparison of tape stripping, the buffer scrub
      method and solvent extraction in in vitro studies. Using this method, climbazole
      deposition in in vitro and in vivo studies was successfully quantified.

PMID- 23958692
TI  - Another glimpse over the salting-out assisted liquid-liquid extraction in
      acetonitrile/water mixtures.
AB  - The use of the salting-out effect in analytical chemistry is very diverse and can
      be applied to increase the volatility of the analytes in headspace extractions,
      to cause the precipitation of proteins in biological samples or to improve the
      recoveries in liquid-liquid extractions. In the latter, the salting-out process
      can be used to create a phase separation between water-miscible organic solvents
      and water. Salting-out assisted liquid-liquid extraction (SALLE) is an
      advantageous sample preparation technique aiming HPLC-UV analysis when developing
      analytical methodologies. In fact, some new extraction methodologies like
      QuEChERS include the SALLE concept. This manuscript discusses another point of
      view over SALLE with particular emphasis over acetonitrile-water mixtures for
      HPLC-UV analysis; the influence of the salting-out agents, their concentration
      and the water-acetonitrile volume ratios were the studied parameters. alpha
      dicarbonyl compounds and beer were used as test analytes and test samples,
      respectively. The influence of the studied parameters was characterized by the
      obtained phase separation volume ratio and the fraction of alpha-dicarbonyls
      extracted to the acetonitrile phase. Results allowed the distribution of salts
      within three groups according to the phase separation and their extractability:
      (1) chlorides and acetates, (2) carbonates and sulfates and (3) magnesium
      sulfate; of all tested salts, sodium chloride had the highest influence on the
      alpha-dicarbonyls fraction extracted. 

PMID- 23958693
TI  - Core shell stationary phases for a novel separation of triglycerides in plant
      oils by high performance liquid chromatography with electrospray-quadrupole-time
      of flight mass spectrometer.
AB  - A new method for the analysis of triglycerides (TAGs) in vegetable oils was
      developed using a Poroshell 120 EC-C18 column (3.0 mm*50 mm, 2.7 MUm) with a high
      resolution ESI-Q-ToF tandem mass spectrometer as detection system. We used an
      Agilent Poroshell column, which is characterized by a recently developed
      stationary phase based on non-porous core particles. The results highlighted the
      advantages of this column in terms of the dramatic improvement in the number of
      theoretical plates and in low column backpressure. The developed method enabled
      us to analyze complex mixtures of more than 40 TAGs within less than 25 min and
      with a low backpressure (lower than 100 bar), and represents the first
      application of a core-shell stationary phase in reverse phase HPLC using an ESI-Q
      ToF as detection system. The method was optimized on standards of TAGs, validated
      and applied to several plant oils. By a quantitative point of view, the method
      showed a very good linearity (r(2)>0.999) in the range 0.1-2.4 MUg/g; high intra-
      and inter-day precision both in terms of retention times (RSD%<0.04%) and peak
      areas (RSD%<0.3%). Limits of detection and quantitation were lower than 0.03
      MUg/g and 0.10 MUg/g, respectively.

PMID- 23958694
TI  - Using glucaminium-based ionic liquids for improving the separation of 2
      aminopyrimidine-5-ylboronic acid and its pinacol ester by high performance liquid
      chromatography.
AB  - A reversed-phase high performance liquid chromatography (HPLC) method is
      described for the determination of boronic acids that are commonly present as
      impurities in pinacolboronate ester reagents. Boronic acids and their
      pinacolboronate esters are key reagents in the Suzuki-Miyaura coupling reaction.
      The retention of hydrophilic boronic acids in reversed-phase chromatography is
      often a challenge, especially in very high pH mobile phases, which are needed to
      mitigate the on-column degradation of pinacolboronate esters. In this study, a
      hydrophilic boronic acid, 2-aminopyrimidine-5-ylboronic acid, was complexed with
      specifically functionalized glucaminium-based ionic liquids that were added to
      the diluent. The two glucaminium-based ILs possess cis-diol moieties that are
      capable of forming complexes with boronic acids. In addition, aromatic functional
      groups within the glucaminium cation allow strong pi-pi interactions with the
      polymeric stationary phase. Using this approach, the limit of detection for 2
      aminopyrimidine-5-ylboronic acid was found to be 3-4MUM. The quantification of 2
      aminopyrimidine-5-ylboronic acid within a 2-aminopyrimidine-5-pinacolboronate
      ester sample was successfully achieved using this method.

PMID- 23958695
TI  - Quality assurance of monoclonal antibody pharmaceuticals based on their charge
      variants using microchip isoelectric focusing method.
AB  - Monoclonal antibody (mAb) pharmaceuticals are much more complex than small
      molecule drugs. Such complex characteristics raise challenging questions for
      regulatory evaluation. Although heterogeneity in mAbs based on their charge
      variants has been mainly evaluated using gel-based isoelectric focusing (IEF)
      method, recent development in capillary electrophoresis and microchip
      electrophoresis has made it possible to assure their heterogeneities in more easy
      and rapid manner. In the present paper, we customized the imaged microchip
      isoelectric focusing (mIEF) for the analysis of mAbs, and compared the customized
      version with the conventional capillary isoelectric focusing (cIEF) method, and
      found that mIEF has much higher performance in operations, and its resolving
      powers are comparable with those obtained by cIEF. 

PMID- 23958696
TI  - Application of surfactant assisted dispersive liquid-liquid microextraction as an
      efficient sample treatment technique for preconcentration and trace detection of
      zonisamide and carbamazepine in urine and plasma samples.
AB  - A simple, rapid, and efficient method, based on surfactant assisted dispersive
      liquid-liquid microextraction (SA-DLLME), followed by high performance liquid
      chromatography (HPLC) has been developed for simultaneous preconcentration and
      trace detection of zonisamide and carbamazepine in biological samples. A
      conventional cationic surfactant called cethyltrimethyl ammonium bromide (CTAB)
      was used as a disperser agent in the proposed approach. 1.5 mL of CTAB (0.45 mmol
      L(-1)) (disperser solvent) containing 50.0 MUL of 1-octanol (extraction solvent)
      was injected rapidly into the 7.0 mL of water or diluted plasma or urine. A
      cloudy solution (water, 1-octanol, and CTAB) was formed in the test tube. After
      formation of cloudy solution, the mixture was centrifuged and 20 MUL of collected
      phase was injected into HPLC for subsequent analysis. Some parameters such as the
      type and volume of the extraction solvent, the type and concentration of
      surfactant, pH, ionic strength and centrifugation time were evaluated and
      optimized. Under optimum extraction conditions, the limits of detections (LODs)
      were 2.1 and 1.5 MUg L(-1) (based on 3Sb/m) for urine samples, and 2.3 and 1.6
      MUg L(-1) for plasma samples. Linear dynamic range of 5-300 and 5-200 MUg L(-1)
      were obtained for zonisamide and carbamazepine in all samples. Finally, the
      applicability of the proposed method was evaluated by extraction and
      determination of the drugs in urine and plasma samples.

PMID- 23958697
TI  - Comparison of large scale purification processes of naproxen enantiomers by
      chromatography using methanol-water and methanol-supercritical carbon dioxide
      mobile phases.
AB  - This paper compares two methods used for the preparative purification of a
      mixture of (S)-, and (R)-naproxen on a Whelk-O1 column, using either high
      performance liquid chromatography or supercritical fluid chromatography. The
      adsorption properties of both enantiomers were measured by frontal analysis,
      using methanol-water and methanol-supercritical carbon dioxide mixtures as the
      mobile phases. The measured adsorption data were modeled, providing the
      adsorption isotherms and their parameters, which were derived from the nonlinear
      fit of the isotherm models to the experimental data points. The model used was a
      Bi-Langmuir isotherm, similar to the model used in many enantiomeric separations.
      These isotherms were used to calculate the elution profiles of overloaded elution
      bands, assuming competitive Bi-Langmuir behavior of the two enantiomers. The
      analysis of these profiles provides the basis for a comparison between
      supercritical fluid chromatographic and high performance liquid chromatographic
      preparative scale separations. It permits an illustration of the advantages and
      disadvantages of these methods and a discussion of their potential performance. 

PMID- 23958699
TI  - Photoresponse enhancement by mixing of an alcohol-soluble C60 derivative into a
      ruthenium complex monolayer.
AB  - We have investigated the effect of mixing an alcohol-soluble C60 derivative into
      a self-assembled monolayer (SAM), which consisted of a redox-active Ru-complex
      with multipoint anchoring groups, on an indium tin oxide surface. Angle-resolved
      X-ray photoelectron spectroscopy of the mixed SAM revealed that the C60
      derivative was well incorporated into the redox-active Ru-complex SAM. In
      addition, some of the C60 derivatives were present on the mixed SAM surface. In
      the presence of a sacrificial reagent, the action spectra of the mixed molecular
      layer exhibited a broad spectral response due to the presence of the C60
      derivative, whereas a sharp response was observed for the monocomponent Ru
      complex SAM. We propose that an efficient charge separation arising from the
      combination of the C60 derivative and the Ru-complex enhanced the spectral
      response of the mixed SAM. 

PMID- 23958698
TI  - Sensitive quantification of gadolinium-based magnetic resonance imaging contrast
      agents in surface waters using hydrophilic interaction liquid chromatography and
      inductively coupled plasma sector field mass spectrometry.
AB  - The application of gadolinium(Gd)-based contrast agents to support medical
      examinations by magnetic resonance imaging (MRI) results in a large input of Gd
      into the environment. The long-term effects of the anthropogenic Gd anomaly,
      especially on aqueous ecosystems, are mostly unknown. The identification and
      quantification of Gd-based contrast agents in the aquatic environment requires
      the use of powerful methods of speciation analysis. Therefore, a method employing
      the hyphenation of hydrophilic interaction liquid chromatography (HILIC) and
      inductively coupled plasma sector field mass spectrometry (ICP-SFMS) with sample
      introduction as dry aerosol generated by desolvation was developed. The
      desolvation resulted in improved limits of detection for the predominantly used
      contrast agents well below 0.10 nmol/L. This method was subsequently used for the
      analysis of Gd species in surface waters. Samples from a nature reserve in the
      city of Munster (Germany), into which the effluent from the city's main
      wastewater treatment plant enters the environment, were examined. The contrast
      agents Gd-DTPA, Gd-DOTA and Gd-BT-DO3A were identified and quantified in constant
      ratios in those samples. The concentrations were found in a range from 0.59
      nmol/L for Gd-DOTA up to 3.55 nmol/L for Gd-BT-DO3A. As a result of mass
      balancing, the contrast agent concentration was found to account for 74-89% of
      total Gd concentrations, possibly indicating the presence of further Gd species.
      Nevertheless, there was no direct indication of species transformation by
      transmetallation reactions resulting in such Gd species. The determination of REE
      patterns by means of ICP-MS confirmed the results of speciation analysis showing
      significant Gd anomalies.

PMID- 23958701
TI  - Structure of polypoidal choroidal vasculopathy studied by colocalization between
      tomographic and angiographic lesions.
AB  - PURPOSE: To investigate the structure of polypoidal choroidal vasculopathy (PCV)
      by tomographic localization of the branching vascular network and late geographic
      hyperfluorescence. DESIGN: Observational case series. METHODS: We examined 34
      eyes with PCV by simultaneous indocyanine green angiography (ICGA) and spectral
      domain optical coherence tomography (OCT) imaging. The margin of the branching
      vascular network and the late geographic hyperfluorescence on ICGA was
      colocalized on OCT, in a point-to-point manner, using innate software. The large
      vessels within the branching vascular network were also colocalized on OCT.
      RESULTS: Late geographic hyperfluorescence on ICGA was noted in 30 eyes. The
      extent of late geographic hyperfluorescence was larger than that of branching
      vascular network in 12 eyes. In the remaining eyes, the extent was the same. A
      double-layer sign on OCT, which consisted of two hyper-reflective lines,
      representing the retinal pigment epithelium and Bruch membrane, was noted in 29
      eyes. In all 28 eyes exhibiting both late geographic hyperfluorescence and the
      double-layer sign, the extent of late geographic hyperfluorescence matched
      exactly the extent of double-layer sign on OCT. In 7 of 34 eyes, the thickness of
      the subretinal pigment epithelial space over the Bruch membrane was too thin to
      accommodate the large vessels of the branching vascular network. Although the
      double-layer sign showed mild reduction in area after photodynamic therapy, its
      general configuration was maintained. CONCLUSIONS: Late geographic
      hyperfluorescence on ICGA corresponds with the double-layer sign on OCT in eyes
      with PCV. Our observations suggest that the double-layer sign consists mainly of
      fibrous tissue harbored by the branching vascular network, and late geographic
      hyperfluorescence may originate from the staining of tissue.

PMID- 23958700
TI  - Mucosal complications of modified osteo-odonto keratoprosthesis in chronic
      Stevens-Johnson syndrome.
AB  - PURPOSE: To describe clinical outcomes of complications afflicting the autologous
      oral mucous membrane graft after modified osteo-odonto keratoprosthesis surgery
      in chronic Stevens-Johnson syndrome (SJS). DESIGN: Prospective case series.
      METHODS: This study included 30 eyes of 30 patients with SJS-induced dry
      keratinized ocular surfaces; the patients underwent various stages of this
      procedure between August 2009 and February 2012. Mucosal complications were
      classified as either necrosis or overgrowth. Mucosal necrosis was managed
      according to a predesigned algorithm based on timing (pre- and postimplantation)
      and location (central or peripheral) of necrosis. Cases with mucosal overgrowth
      underwent mucosal debulking and trimming. RESULTS: Mucosal necrosis developed in
      15 (50%) eyes and overgrowth in 4 (13.3%) eyes. Preimplantation necrosis (n = 7)
      was initially managed conservatively, but 2 eyes required free labial-mucous
      membrane grafting for persistent corneal exposure. Free labial-mucous membrane
      grafting was performed in all cases of postimplantation necrosis (n = 10), but 8
      eyes required additional tarsal pedicle flaps (n = 6, for peripheral necrosis) or
      through-the-lid revisions (n = 2, for central necrosis). Debulking and trimming
      effectively managed all cases of mucosal overgrowth, but 3 eyes required repeat
      procedures. At 24.1 +/- 6.5 months postimplantation, the keratoprosthesis was
      retained in all eyes, and the probability of maintaining 20/60 or better vision
      was similar in eyes with or without mucosal necrosis (86 +/- 8.8% vs 80 +/-
      10.3%). CONCLUSIONS: Mucosal complications, especially necrosis, occurred
      commonly following modified osteo-odonto keratoprosthesis surgery in dry
      keratinized post-SJS eyes. The algorithm-based management approach described in
      this study was successful in treating these complications, retaining the
      prosthesis and preserving useful vision.

PMID- 23958702
TI  - Comparative metabolism of benfuracarb in in vitro mammalian hepatic microsomes
      model and its implications for chemical risk assessment.
AB  - In vitro metabolism of benfuracarb in liver microsomes from seven species was
      studied in order to quantitate species-specific metabolic profiles and enhance
      benfuracarb risk assessment by interspecies comparisons. Using LC-MS/MS, a total
      of seven phase-I-metabolites were detected from the extracted chromatograms and
      six of them were unequivocally identified. Benfuracarb was metabolized via two
      metabolic pathways, the sulfur oxidation pathway and nitrogen sulfur bond
      cleavage, yielding carbofuran, which metabolized further. Analysis of the
      metabolic profiles showed that benfuracarb was extensively metabolized with
      roughly similar profiles in different species in vitro. In vitro intrinsic
      clearance rates as well as calculated in vivo hepatic clearances indicated that
      all seven species metabolize benfuracarb via the carbofuran metabolic pathway
      more rapidly than the sulfoxidation pathway. The highest interspecies differences
      in hepatic clearance rate values were for mouse and rat liver microsomes compared
      to human, i.e. 4.8 and 4.1-fold higher, as illustrated by in vivo hepatic
      clearance of carbofuran. Overall, there are quantitative interspecies differences
      in the metabolic profiles and kinetics of benfuracarb biotransformation. These
      findings illustrate that in vitro studies of benfuracarb metabolite profiles and
      toxicokinetics are helpful for the proper selection and interpretation of animal
      models for toxicological evaluation and chemical risk assessment. 

PMID- 23958703
TI  - HLA shared epitope and ACPA: just a marker or an active player?
AB  - Autoantibody production is genetically controlled and anti-citrullinated
      protein/peptide antibodies (ACPA) are not an exception to the rule. ACPA are
      highly specific markers of rheumatoid arthritis (RA) and are also associated with
      a more severe disease course. The production of ACPA is almost invariably
      observed in HLA-shared epitope (SE) positive patients. The DRB1 alleles sharing
      SE are those conferring susceptibility to RA. SE alleles behave like immune
      response genes, controlling both the specificity and the amount of ACPA produced.
      These data suggest a role of SE in the presentation of citrullinated antigens.
      The ability of SE alleles to bind selectively to citrullinated sequences as
      compared to the native counterparts has been demonstrated in the case of peptides
      derived from several joint associated proteins (vimentin, fibrinogen and
      cartilage intermediate-layer protein). On the contrary, EBV-derived citrullinated
      peptides do not display a biologically relevant binding to SE alleles even if the
      immune response to VCPs is under the genetic control of these alleles (namely
      *0401 and *0404). Thus, the presentation of citrullinated epitopes does not
      represent the only molecular mechanisms underlying the HLA-DRB1 effect on ACPA
      production. 

PMID- 23958704
TI  - [Clinical evaluation of the Tonovet(r) reboundtonometer in dogs and cats
      considering potential errors in handling].
AB  - OBJECTIVE: To evaluate the Tonovet(r) rebound tonometer in a larger number of
      dogs and cats free of ocular disease and to examine the impact of handling errors
      of the tonometer. MATERIAL AND METHODS: In 100 ophthalmologically healthy dogs (n
      = 80) and cats (n = 20) of different breeds (beagle, dachshund, retriever,
      brachycephalic dogs, domestic shorthair cats), the intraocular pressure (IOP) was
      measured bilaterally using the Tonovet(r) according to the manufacturer's
      instructions. Subsequently, different aspects of handling/positioning were
      altered (localisation and angle of impact, distance of probe to corneal surface).
      Finally a comparative measurement was made using the Tonopen Vet(r) applanation
      tonometer. RESULTS: Mean IOP +/- standard deviation (SD) in the dogs (160 eyes)
      was 13,7 +/- 2.9 mmHg for the Tonovet(r) and 12.9 +/- 3.1 mmHg for the Tonopen
      Vet(r). In the cats (40 eyes) a IOP value of 16.7 mmHg +/- 3.0 mmHg was obtained
      with the Tonovet(r) and 17.4 mmHg +/- 3.0 mmHg with the Tonopen Vet(r). Deviation
      from the manufacturer's recommendations on handling the Tonovet(r) during the
      measurement significantly affected the results obtained. Compared to the
      reference measurement, directing the Tonovet(r) onto the peripheral cornea
      (approximately 1.5 mm from the limbus) as well as reducing the measuring distance
      to <4 mm resulted in slightly elevated IOP readings. Substantial underestimation
      of IOP occurred with angular deviation of the measuring axis. CONCLUSION AND
      CLINICAL RELEVANCE: The Tonovet(r) rebound tonometer proved to be a valuable
      alternative to conventional tonometers for clinical use in dogs and cats. It is
      well tolerated by both canine and feline patients. However, the use of the
      Tonovet(r) in a clinical setting requires the examiner to consider potential
      sources of error when handling the tonometer to avoid false IOP readings.

PMID- 23958705
TI  - [Cisterna chyli ablation in three cats with idiopathic chylothorax].
AB  - OBJECTIVE: Presentation of three cats with chronic, idiopathic chylothorax
      treated with ablation of the cisterna chyli as an additional or a sole surgical
      treatment. MATERIAL AND METHODS: Results of clinical and diagnostic examination,
      therapy and course of disease in three cats as well as the surgical technique of
      ablation of the cisterna chyli in cats are described. RESULTS: There were no
      intraoperative or postoperative complications regarding cisterna chyli ablation.
      Intraoperative visualization of the cisterna chyli is easily achieved by
      administering a small portion of a fatty aliment preoperatively or by injection
      of diluted methylene blue into the lymphatic system intraoperatively. Ablation of
      the cisterna chyli was performed following an unsuccessful ligation of the
      thoracic duct, in combination with the ligation of the thoracic duct and subtotal
      pericardectomy or as a single surgical treatment. CLINICAL RELEVANCE: Cisterna
      chyli ablation can be performed without complications in cats. This technique
      should be considered in cases of previously failed surgical therapy or as an
      adjunct therapy used with other surgical options to decrease the risk of
      recurrence.

PMID- 23958706
TI  - [Decision making in veterinary practice].
AB  - OBJECTIVE: In daily practice, a veterinarian has to judge information and decide
      whether it can be adequately implemented for a given case. In this context, it is
      vital to base decisions on the most recent and reliable scientific findings. In
      Germany, every practitioner must take part in 20 to 40 hours annually of
      continuing education. To outline the current assessment and employment of
      evidence-based veterinary medicine (EBVM), we surveyed practitioners concerning
      continuing education and their skills in obtaining and evaluating scientific
      information. MATERIALS AND METHODS: A survey amongst veterinary practitioners was
      conducted throughout five continuing education courses between May 2010 and
      November 2011. The questionnaire contained 32 questions concerning demographic
      data and profession (n = 4), qualification (n = 3), continuing education (n = 5)
      and skills related to EBVM (n = 20). Besides evaluating the statements of all
      participants, veterinarians were classified based on the type of practice and
      their statements compared. RESULTS: In total, 293 questionnaires were returned.
      The majority of small animal practitioners (58.3%) and those working with food
      animals (54.9%) declared being capable of comprehending scientific talks or
      papers in English without difficulty. 10.4% of all practitioners neglected
      reading veterinary journals on a regular basis, while 20.8% stated they regularly
      read English veterinary journals. The majority of the practitioners sought advice
      from their employer or a colleague. They attributed a high or very high quality
      to both these information sources. Almost every participant (92.6%) stated that
      they consulted medical books, and 88.6% certified this information source as
      being of high or very high quality. 68.6% of the practitioners evaluated their
      skills in finding suitable literature as high or very high. However, only
      approximately half (52.1%) of all participants attributed themselves a high
      ability to evaluate the quality of the literature found. CONCLUSION AND CLINICAL
      RELEVANCE: Most practitioners are very limited in their ability to assess the
      evidence of scientific information. Therefore, courses that introduce EBVM should
      be taught in both veterinary and postgraduate education to train critical
      appraisal of information and to support decision-making based on valid,
      clinically relevant data.

PMID- 23958707
TI  - [New drugs for small animals in 2012].
AB  - In 2012, three active pharmaceutical ingredients were released on the German
      market for small animals. These are the anti-thyroid Carbimazole (Vidalta(r)),
      the opium-derived analgesic Fentanyl (Fentadon(r)) and the antiepileptic
      Potassium Bromide (Libromide(r)). One substance was authorized for an additional
      species. The insecticide Flumethrin in combination with Imidacloprid is now also
      authorized for use in cats. Furthermore, this preparation includes an interesting
      new pharmaceutical form for dogs and cats and a new combination of active
      pharmaceutical ingredients for dogs. In addition, three active pharmaceutical
      ingredients with approval for use in human medicine, which are of potential
      interest to veterinary medicine, entered the market in 2012. These are the
      antidiabetic Dapagliflozin, the antiepileptic Perampanel and the Somatostatin
      analog Pasireotide. 

PMID- 23958708
TI  - [Use of gold implants as a treatment of pain related to canine hip dysplasia--a
      review. Part 2: Clinical trials and case reports].
AB  - Gold bead implantation/gold acupuncture is becoming increasingly used in
      veterinary medicine as a method of pain treatment in cases of osteoarthritic
      diseases. Part one of the overview dealing with the use of gold implants as a
      treatment of canine hip joint dysplasia (cHD) introduced the method of implanting
      gold in tissue and publications which investigated the subsequent effects of
      implantation. This article focuses on publications concerning the clinical
      effectiveness of gold implantation within the scope of pain therapy in cHD. Due
      to the study design, a classification using evidence-based levels (EbL) was
      carried out. Three double-blind, placebo-controlled randomised studies (EbL II)
      were considered together with three retrospective studies on own patients (EbL
      IV) and five case studies (EbL IV). While the case and retrospective studies
      reported impressive therapeutic success in treating cHD-incurred pain with gold
      implantation, a pain-reducing effect through gold implantation was only
      demonstrated in one of the three double-blind studies. The two remaining EbL II
      studies found no differences between the placebo-group and the group of dogs
      treated with gold implantation. In one of these two studies, kinematic and
      kinetic gait analyses were used for objective evaluation of the effects of the
      treatment. Thus, the only study that carried out an objective evaluation of the
      therapeutic result of gold implantation came to the conclusion that the method is
      ineffective. For a concluding assessment of gold implantation in the case of cHD,
      gait analysis studies investigating the effects of gold implantation in
      comparison to a standard treatment with nonsteroidal anti-inflammatory drugs are
      currently lacking. 

PMID- 23958709
TI  - Cutaneous paraneoplastic syndrome in a cat with thymoma.
AB  - Feline cutaneous paraneoplastic syndrome is a rare disorder associated mainly
      with pancreatic carcinoma and thymoma. In this report the authors describe the
      case of a 12-year-old cat with paraneoplastic exfoliative dermatitis associated
      with thymoma. Lateral radiographic examination of the chest showed a small subtle
      soft tissue density in the ventral part of the first and second intercostal
      space, which together with skin changes suggested thymoma. Because of pain
      associated with the skin condition, costs of treatment and the risk associated
      with surgical treatment, the owner chose euthanasia of the cat. Post-mortem
      examination revealed a tumour which was diagnosed as thymoma by histopathological
      examination. 

PMID- 23958710
TI  - Laser therapy in a soft-shelled turtle (Pelodiscus sinensis) for the treatment of
      skin and shell ulceration. A case report.
AB  - Skin and shell diseases in aquatic turtles are often associated with several
      underlying causes. The presented case report describes aetiology including
      differential diagnoses, diagnostic procedures and therapy of a soft-shelled
      turtle (Pelodiscus sinensis) suffering from a septicaemic ulcerative dermatitis.
      Central aspect hereby is the positive curing effect of laser therapy on skin and
      shell lesions. 

PMID- 23958711
TI  - [Exfoliative vaginal cytology in the bitch--indications, procedure,
      interpretation].
AB  - Exfoliative vaginal cytology as an essential part of the gynaecological
      examination is a simple, non-invasive method for the determination of the phases
      of the oestrous cycle (anoestrus, prooestrus/oestrus, metoestrus) and is
      additionally applied in cases of silent heat, or suspected ovarian cysts, ovarian
      remnant syndrome, postpartal disturbances in the endometrial involution or
      Sticker sarcoma. The exfoliated cells reflect the hormonal, in particular the
      oestrogenic state, of the bitch. Due to the oestrogenic influence, an increase in
      cell layers, keratinisation and exfoliation is observed in the follicular phase
      during prooestrus, such that the 3-4 layered epithelium in anoestrus becomes 20
      layered during oestrus. The cells change characteristically in size and nuclear
      morphology. In anoestrus, predominantly parabasal cells with a large nucleus and
      homogenous cytoplasm are found. During early prooestrus, single parabasal cells
      are identified among erythrocytes and intermediate cells. As this phase
      progresses, the percentage of large intermediate cells and nucleated superficial
      cells increases. The oestrus is characterised by a high cell number, initially
      superficial cells with pyknotic nuclei, later anucleated squamous cells that are
      located in cell nests. The switch to metoestrus is associated with a large number
      of neutrophil granulocytes and a sudden change of cytology within 24-48 hours.
      Vaginal cytology can be performed in any practice due to its simplicity and the
      limited equipment necessary (speculum, cotton wool wad, slide, staining and
      microscope). Because the results are rapidly available, it is a useful addition
      to gynaecological examination to differentiate the stage of the cycle (anoestrus,
      prooestrus/oestrus, metoestrus) and to diagnose infectious, inflammatory and
      tumorous conditions in the bitch. 

PMID- 23958712
TI  - Effects of a nanoscale silica matrix on the fluorescence quantum yield of
      encapsulated dye molecules.
AB  - The effects that nanometer-sized matrices have on the properties of molecules
      encapsulated within the nanomatrix are not fully understood. In this work, dye
      doped silica nanoparticles were employed as a model for studying the effects of a
      nanomatrix on the fluorescence quantum yield of encapsulated dye molecules. Two
      types of dye molecules were selected based on their different responses to the
      surrounding media. Several factors that affect fluorescence quantum yields were
      investigated, including aggregation of dye molecules, diffusion of atmospheric
      oxygen, concentration of dye molecules, and size of the nanomatrix. The results
      showed that the silica nanomatrix has a varied effect on the fluorescence quantum
      yield of encapsulated dye molecules, including enhancement, quenching and
      insignificant changes. Both the properties of dye molecules and the conditions of
      the nanomatrix played important roles in these effects. Finally, a physical model
      was proposed to explain the varied nanomatrix effects on the fluorescence quantum
      yield of encapsulated dye molecules. 

PMID- 23958714
TI  - Central vault in dry eye patients successfully wearing scleral lens.
AB  - PURPOSE: Scleral contact lenses are used to treat symptoms of severe dry eyes.
      Procedures for fitting scleral lenses have been vague because of lack of
      standardized guidelines. This retrospective case series sought to establish
      average vault over central cornea in successful scleral lens wearers with dry
      eyes. METHODS: Anterior segment optical coherence tomography was used to measure
      the distance between the posterior lens surface and cornea in 20 eyes of 12
      consecutive patients successfully fit in the Vanderbilt Scleral Lens Clinic.
      RESULTS: Mean vault was 380 +/- 110 MUm. There was no correlation between vault
      and corneal curvature or vault and visual acuity. CONCLUSIONS: With a large SD in
      average vault, precision in central vault does not seem to be important in
      scleral contact lenses for successful fit for dry eyes.

PMID- 23958715
TI  - The 2012 Charles Prentice medal lecture: wavefront measurement of refractive
      state.
AB  - Modern efforts to define and measure the refractive state of aberrated eyes have
      led to new insights about the nature of refractive error, the quality of the
      retinal image, the interplay of the crystalline lens, and the eye's pupil during
      accommodation. Our change in mind-set engendered by wavefront concepts has the
      power to alter our way of thinking about many clinical issues that are
      fundamentally optical in nature, such as dynamic changes in optical quality of
      eyes caused by tear film deterioration, outcome assessment of refractive
      therapies, and myopia progression. The aim of this lecture is to help make
      advances in these areas of optometric science broadly accessible to educators,
      clinicians, and patients by explaining in simple terms the underlying optical
      concepts of wavefront aberrometry.

PMID- 23958713
TI  - Relationship between clinical signs and symptoms of convergence insufficiency.
AB  - PURPOSE: The percentage of children who are symptomatic has been shown to
      increase with the number of signs of convergence insufficiency (CI). Our goal was
      to investigate whether there is a relationship between the severity of the
      clinical signs of CI and symptom level reported in children with a three-sign
      symptomatic CI. METHODS: The Convergence Insufficiency Treatment Trial enrolled
      221 children with symptomatic CI from ages 9 to 17 years. Inclusion criteria
      included the following three signs of CI: (1) exophoria at near at least 4Delta
      greater than at distance, (2) insufficient positive fusional vergence (PFV) at
      near, and (3) a receded near point of convergence (NPC) of 6 cm break or greater.
      The relationships between the severity of each sign of CI (mild, moderate, and
      severe) and the level of symptoms as measured by the Convergence Insufficiency
      Symptom Survey (CISS) at baseline were evaluated. RESULTS: Mean CISS scores were
      not significantly different between mild, moderate, and severe exophoria (p =
      0.60), PFV blur (p = 0.99), Sheard's criterion (p = 0.89), or NPC break (p =
      0.84). There was also no difference between the frequency of subjects scoring at
      mild, moderate, or severe levels on the CISS and the severity of each sign of CI.
      Correlations between individual clinical signs and the CISS score were very low
      and not statistically significant. CONCLUSIONS: Among symptomatic children with a
      CISS score of 16 or higher and three clinical signs of CI, there is no further
      association between the severity of the clinical signs and their level of
      symptoms.

PMID- 23958716
TI  - Effect of rituximab in MCNS: a role for IL-13 suppression?

PMID- 23958717
TI  - Acute kidney injury: Ultrasound may be useful in preventing acute kidney injury.

PMID- 23958724
TI  - A new statistic for identifying batch effects in high-throughput genomic data
      that uses guided principal component analysis.
AB  - MOTIVATION: Batch effects are due to probe-specific systematic variation between
      groups of samples (batches) resulting from experimental features that are not of
      biological interest. Principal component analysis (PCA) is commonly used as a
      visual tool to determine whether batch effects exist after applying a global
      normalization method. However, PCA yields linear combinations of the variables
      that contribute maximum variance and thus will not necessarily detect batch
      effects if they are not the largest source of variability in the data. RESULTS:
      We present an extension of PCA to quantify the existence of batch effects, called
      guided PCA (gPCA). We describe a test statistic that uses gPCA to test whether a
      batch effect exists. We apply our proposed test statistic derived using gPCA to
      simulated data and to two copy number variation case studies: the first study
      consisted of 614 samples from a breast cancer family study using Illumina Human
      660 bead-chip arrays, whereas the second case study consisted of 703 samples from
      a family blood pressure study that used Affymetrix SNP Array 6.0. We demonstrate
      that our statistic has good statistical properties and is able to identify
      significant batch effects in two copy number variation case studies. CONCLUSION:
      We developed a new statistic that uses gPCA to identify whether batch effects
      exist in high-throughput genomic data. Although our examples pertain to copy
      number data, gPCA is general and can be used on other data types as well.
      AVAILABILITY AND IMPLEMENTATION: The gPCA R package (Available via CRAN) provides
      functionality and data to perform the methods in this article. CONTACT:
      reesese@vcu.edu

PMID- 23958719
TI  - Nephrology in Africa--not yet uhuru.
AB  - Nephrology is a 'Cinderella speciality', a disregarded area of health care, in
      Africa. Other health issues have relegated the treatment of kidney diseases to a
      low priority status, and the cost of treating the more common and widespread
      communicable diseases, financial mismanagement and corruption in many countries
      has sounded the death knell for expensive therapies such as dialysis. The
      communicable diseases that have devastated the health systems around Africa are
      tuberculosis and HIV/AIDS. Until recently, very little information was available
      on the impact of HIV on acute and chronic dialysis admissions. Patients with
      acute kidney injury (AKI) in most of Africa are seldom treated because of great
      distances to travel, lack of expertise, poverty and poor sustainable funding for
      health matters. An acute peritoneal dialysis (PD) programme has now been
      initiated in Tanzania but the sustainability of this project will be tested in
      the future. The International Society of Nephrology (ISN) has developed a
      training programme for nephrologists from developing countries, which may now be
      bearing fruit. A report from the sub-Saharan Africa region shows that the numbers
      of patients on dialysis and those diagnosed with chronic kidney disease (CKD) has
      increased significantly. Other ISN-sponsored programmes such as Continuing
      Medical Education activities for physicians and community screening projects have
      had far-reaching positive effects. Government funding for a dialysis programme is
      well established in South Africa, but this funding is limited so that the numbers
      accepted for public dialysis are restricted. Consequently in the Western Cape
      province of South Africa, a 'category system' has been formulated to attempt to
      cope with this unacceptable and restrictive ruling. 

PMID- 23958726
TI  - RDAVIDWebService: a versatile R interface to DAVID.
AB  - SUMMARY: The RDAVIDWebService package provides a class-based interface from R
      programs/scripts to fully access/control the database for annotation,
      visualization and integrated discovery, without the need for human interaction on
      its Web site (http://david.abcc.ncifcrf.gov). The library enhances the database
      for annotation, visualization and integrated discovery capabilities for Gene
      Ontology analysis by means of GOstats-based direct acyclic graph conversion
      methods, in addition to the usual many-genes-to-many-terms visualization.
      AVAILABILITY AND IMPLEMENTATION: RDAVIDWebService is available as an R package
      from the Bioconductor project (www.bioconductor.org) and on the authors' Web site
      (www.bdmg.com.ar) under GPL-2 license, subjected to the terms of use of DAVID
      (http://david.abcc.ncifcrf.gov/content.jsp?file=WS.html). CONTACT:
      cfresno@bdmg.com.ar or efernandez@bdmg.com.ar.

PMID- 23958725
TI  - PRAP: an ab initio software package for automated genome-wide analysis of DNA
      repeats for prokaryotes.
AB  - MOTIVATION: Prokaryotic genome annotation has been focused mainly on identifying
      all genes and their protein functions. However, <30% of the prokaryotic genomes
      submitted to GenBank contain partial repeat features of specific types and none
      of the genomes contain complete repeat annotations. Deciphering all repeats in
      DNA sequences is an important and open task in genome annotation and
      bioinformatics. Hence, there is an immediate need of a tool capable of
      identifying full spectrum repeats in the whole genome. RESULTS: We report the
      PRAP (Prokaryotic Repeats Annotation Program software package to automate the
      analysis of repeats in both finished and draft genomes. It is aimed at
      identifying full spectrum repeats at the scale of the prokaryotic genome.
      Compared with the major existing repeat finding tools, PRAP exhibits competitive
      or better results. The results are consistent with manually curated and
      experimental data. Repeats can be identified and grouped into families to define
      their relevant types. The final output is parsed into the European Molecular
      Biology Laboratory (EMBL)/GenBank feature table format for reading and displaying
      in Artemis, where it can be combined or compared with other genome data. It is
      currently the most complete repeat finder for prokaryotes and is a valuable tool
      for genome annotation. AVAILABILITY: https://sites.google.com/site/prapsoftware/
      CONTACT: hsuehc@ntu.edu.tw. SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 23958727
TI  - Efficient inference of local ancestry.
AB  - MOTIVATION: The inference of local ancestry of admixed individuals at every locus
      provides the basis for admixture mapping. Local ancestry information has been
      used to identify genetic susceptibility loci. RESULTS: In this study, we
      developed a statistical method, efficient inference of local ancestry (EILA),
      which uses fused quantile regression and k-means classifier to infer the local
      ancestry for admixed individuals. We also conducted a simulation study using
      HapMap data to evaluate the performance of EILA in comparison with two competing
      methods, HAPMIX and LAMP. In general, the performance declined as the ancestral
      distance decreased and the time since admixture increased. EILA performed as well
      as the other two methods in terms of computational efficiency. In the case of
      closely related ancestral populations, all the three methods performed poorly.
      Most importantly, when the ancestral distance was large or moderate, EILA had
      higher accuracy and lower variation in comparison with the other two methods.
      AVAILABILITY AND IMPLEMENTATION: EILA is implemented as an R package, which is
      freely available from the Comprehensive R Archive Network (http://cran.r
      project.org/). CONTACT: jyangstat@gmail.com.

PMID- 23958728
TI  - A pattern matching approach to the automatic selection of particles from low
      contrast electron micrographs.
AB  - MOTIVATION: Structural information of macromolecular complexes provides key
      insights into the way they carry out their biological functions. Achieving high
      resolution structural details with electron microscopy requires the
      identification of a large number (up to hundreds of thousands) of single
      particles from electron micrographs, which is a laborious task if it has to be
      manually done and constitutes a hurdle towards high-throughput. Automatic
      particle selection in micrographs is far from being settled and new and more
      robust algorithms are required to reduce the number of false positives and false
      negatives. RESULTS: In this article, we introduce an automatic particle picker
      that learns from the user the kind of particles he is interested in. Particle
      candidates are quickly and robustly classified as particles or non-particles. A
      number of new discriminative shape-related features as well as some statistical
      description of the image grey intensities are used to train two support vector
      machine classifiers. Experimental results demonstrate that the proposed method:
      (i) has a considerably low computational complexity and (ii) provides results
      better or comparable with previously reported methods at a fraction of their
      computing time. AVAILABILITY: The algorithm is fully implemented in the open
      source Xmipp package and downloadable from http://xmipp.cnb.csic.es.

PMID- 23958729
TI  - iBMQ: a R/Bioconductor package for integrated Bayesian modeling of eQTL data.
AB  - MOTIVATION: Recently, mapping studies of expression quantitative loci (eQTL)
      (where gene expression levels are viewed as quantitative traits) have provided
      insight into the biology of gene regulation. Bayesian methods provide natural
      modeling frameworks for analyzing eQTL studies, where information shared across
      markers and/or genes can increase the power to detect eQTLs. Bayesian approaches
      tend to be computationally demanding and require specialized software. As a
      result, most eQTL studies use univariate methods treating each gene
      independently, leading to suboptimal results. RESULTS: We present a powerful,
      computationally optimized and free open-source R package, iBMQ. Our package
      implements a joint hierarchical Bayesian model where all genes and SNPs are
      modeled concurrently. Model parameters are estimated using a Markov chain Monte
      Carlo algorithm. The free and widely used openMP parallel library speeds up
      computation. Using a mouse cardiac dataset, we show that iBMQ improves the
      detection of large trans-eQTL hotspots compared with other state-of-the-art
      packages for eQTL analysis. AVAILABILITY: The R-package iBMQ is available from
      the Bioconductor Web site at http://bioconductor.org and runs on Linux, Windows
      and MAC OS X. It is distributed under the Artistic Licence-2.0 terms. CONTACT:
      christian.deschepper@ircm.qc.ca or rgottard@fhcrc.org. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 23958730
TI  - HippDB: a database of readily targeted helical protein-protein interactions.
AB  - SUMMARY: HippDB catalogs every protein-protein interaction whose structure is
      available in the Protein Data Bank and which exhibits one or more helices at the
      interface. The Web site accepts queries on variables such as helix length and
      sequence, and it provides computational alanine scanning and change in solvent
      accessible surface area values for every interfacial residue. HippDB is intended
      to serve as a starting point for structure-based small molecule and
      peptidomimetic drug development. AVAILABILITY AND IMPLEMENTATION: HippDB is
      freely available on the web at http://www.nyu.edu/projects/arora/hippdb. The Web
      site is implemented in PHP, MySQL and Apache. Source code freely available for
      download at http://code.google.com/p/helidb, implemented in Perl and supported on
      Linux. CONTACT: arora@nyu.edu.

PMID- 23958731
TI  - A fast Peptide Match service for UniProt Knowledgebase.
AB  - SUMMARY: We have developed a new web application for peptide matching using
      Apache Lucene-based search engine. The Peptide Match service is designed to
      quickly retrieve all occurrences of a given query peptide from UniProt
      Knowledgebase (UniProtKB) with isoforms. The matched proteins are shown in
      summary tables with rich annotations, including matched sequence region(s) and
      links to corresponding proteins in a number of proteomic/peptide spectral
      databases. The results are grouped by taxonomy and can be browsed by organism,
      taxonomic group or taxonomy tree. The service supports queries where isobaric
      leucine and isoleucine are treated equivalent, and an option for searching
      UniRef100 representative sequences, as well as dynamic queries to major proteomic
      databases. In addition to the web interface, we also provide RESTful web
      services. The underlying data are updated every 4 weeks in accordance with the
      UniProt releases. AVAILABILITY:
      http://proteininformationresource.org/peptide.shtml. CONTACT: chenc@udel.edu.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 23958732
TI  - Liver transplantation and inflammation: is lipopolysaccharide binding protein the
      link?
AB  - BACKGROUND: Lipopolysaccharide (LPS) binding protein (LBP) is an acute phase
      protein, which upregulated in response to surgical interventions. LBP plays an
      important role in modulating LPS-induced inflammatory response. We investigated
      the expression of LBP and the translocation of LPS in rat models of hepatic
      ischemia reperfusion injury and liver transplantation (LTx). We also elucidated
      the effect of LBP on the inflammatory response. METHODS: In this study, cold
      ischemia (CI), warm ischemia/reperfusion (WI/R), and LTx models were used to
      model relevant physiologic situations during LTx. Serum and effluent protein
      levels as well as hepatic-mRNA and protein levels of LBP were examined. LBP
      released into the effluent during CI was used in a macrophage-LPS-stimulation
      assay to investigate the role of LBP in modulating the LPS-induced inflammatory
      response. Blocking experiments using an LBP-inhibitory peptide were performed to
      confirm the relevance of LPS/LBP for the induction of the inflammatory response.
      Impairment of the intestinal barrier and translocation of LPS into the liver was
      visualized by immunohistochemistry. Induction of tumor necrosis factor-alpha (TNF
      alpha) mRNA expression in the liver was taken as indicator of the inflammatory
      response. RESULTS: Upregulation of LBP in serum and/or liver tissue was observed
      after WI/R, CI and LTx, respectively. The LBP released during CI enhanced the LPS
      induced inflammatory response in vitro as indicated by an induction of TNF-alpha.
      On the other hand, blocking LBP using LBP inhibitory peptide, suppressed the
      induction of TNF-alpha in vitro markedly. After LTx, elevated serum LBP levels
      were associated with post-operative LPS translocation and production of
      inflammatory cytokines. CONCLUSIONS: Our findings suggest that translocation of
      LPS occurs after LTx and that LBP is mediating the LPS-induced inflammatory
      response after LTx. Blocking LBP using LBP-inhibitory peptide might represent a
      novel strategy to reduce the I/R-induced inflammatory response.

PMID- 23958733
TI  - Hypocapnia in patients with chronic neck pain: association with pain, muscle
      function, and psychologic states.
AB  - OBJECTIVE: The aim of this study was to investigate whether patients with chronic
      neck pain have changes in their transcutaneous partial pressure of arterial
      carbon dioxide (PtcCO2) and whether other physical and psychologic parameters are
      associated. DESIGN: In this cross-sectional study, 45 patients with chronic
      idiopathic neck pain and 45 healthy sex-, age-, height-, and weight-matched
      controls were voluntarily recruited. The participants' neck muscle strength,
      endurance of the deep neck flexors, neck range of movement, forward head posture,
      psychologic states (anxiety, depression, kinesiophobia, and catastrophizing),
      disability, and pain were assessed. PtcCO2 was assessed using transcutaneous
      blood gas monitoring. RESULTS: The patients with chronic neck pain presented
      significantly reduced PtcCO2 (P < 0.01). In the patients, PtcCO2 was
      significantly correlated with strength of the neck muscles, endurance of the deep
      neck flexors, kinesiophobia, catastrophizing, and pain intensity (P < 0.05). Pain
      intensity, endurance of the deep neck flexors, and kinesiophobia remained as
      significant predictors into the regression model of PtcCO2. CONCLUSIONS: Patients
      with chronic neck pain present with reduced PtcCO2, which can reach the limits of
      hypocapnia. This disturbance seems to be associated with physical and psychologic
      manifestations of neck pain. These findings can have a great impact on various
      clinical aspects, notably, patient assessment, rehabilitation, and drug
      prescription.

PMID- 23958735
TI  - One-step electrochemical synthesis of 6-amino-4-hydroxy-2-napthalene-sulfonic
      acid functionalized graphene for green energy storage electrode materials.
AB  - A green approach for the one-step electrochemical synthesis of water dispersible
      graphene is reported. An alkaline solution of 6-amino-4-hydroxy-2-naphthalene
      sulfonic acid (ANS) serves the role of electrolyte as well as surface modifier.
      High-purity graphite rods are used as electrodes which can be exfoliated under a
      constant electrical potential (~20 V) to form ANS functionalized graphene (ANEG).
      The aqueous dispersion of ANEG obeyed Beer's law at moderate concentrations, as
      evidenced from ultraviolet-visible spectroscopy analysis. X-ray diffraction
      analysis suggests complete exfoliation of graphite into graphene. Fourier
      transform infrared and x-ray photoelectron spectroscopy not only confirm the
      functionalization of graphene with ANS, but also suggest the formation of oxygen
      containing functional groups on the surface of ANEG. Raman spectra analysis
      indicates the presence of defects in ANEG as compared to pure graphite. Cyclic
      voltammetry and charge-discharge measurements of ANEG using three electrode
      systems show a specific capacitance of 115 F g(-1) at a current density of 4 A g(
      1). The ANEG electrode exhibits 93% retention in specific capacitance after 1000
      charge-discharge cycles, confirming its utility as a green energy storage
      electrode material.

PMID- 23958734
TI  - Incorporating new technologies into toxicity testing and risk assessment: moving
      from 21st century vision to a data-driven framework.
AB  - Based on existing data and previous work, a series of studies is proposed as a
      basis toward a pragmatic early step in transforming toxicity testing. These
      studies were assembled into a data-driven framework that invokes successive tiers
      of testing with margin of exposure (MOE) as the primary metric. The first tier of
      the framework integrates data from high-throughput in vitro assays, in vitro-to
      in vivo extrapolation (IVIVE) pharmacokinetic modeling, and exposure modeling.
      The in vitro assays are used to separate chemicals based on their relative
      selectivity in interacting with biological targets and identify the concentration
      at which these interactions occur. The IVIVE modeling converts in vitro
      concentrations into external dose for calculation of the point of departure (POD)
      and comparisons to human exposure estimates to yield a MOE. The second tier
      involves short-term in vivo studies, expanded pharmacokinetic evaluations, and
      refined human exposure estimates. The results from the second tier studies
      provide more accurate estimates of the POD and the MOE. The third tier contains
      the traditional animal studies currently used to assess chemical safety. In each
      tier, the POD for selective chemicals is based primarily on endpoints associated
      with a proposed mode of action, whereas the POD for nonselective chemicals is
      based on potential biological perturbation. Based on the MOE, a significant
      percentage of chemicals evaluated in the first 2 tiers could be eliminated from
      further testing. The framework provides a risk-based and animal-sparing approach
      to evaluate chemical safety, drawing broadly from previous experience but
      incorporating technological advances to increase efficiency. 

PMID- 23958737
TI  - CYP2D6 genotyping and the use of tamoxifen in breast cancer.

PMID- 23958736
TI  - Concordance between CYP2D6 genotypes obtained from tumor-derived and germline
      DNA.
AB  - Formalin-fixed, paraffin-embedded tumors (FFPETs) are a valuable source of DNA
      for genotype association studies and are often the only germline DNA resource
      from cancer clinical trials. The anti-estrogen tamoxifen is metabolized into
      endoxifen by CYP2D6, leading to the hypothesis that patients with certain CYP2D6
      genotypes may not receive benefit because of their inability to activate the
      drug. Studies testing this hypothesis using FFPETs have provided conflicting
      results. It has been postulated that CYP2D6 genotype determined using FFPET may
      not be accurate because of somatic tumor alterations. In this study, we
      determined the concordance between CYP2D6 genotypes generated using 3 tissue
      sources (FFPETs; formalin-fixed, paraffin-embedded unaffected lymph nodes
      [FFPELNs]; and whole blood cells [WBCs]) from 122 breast cancer patients.
      Compared with WBCs, FFPET and FFPELN genotypes were highly concordant (>94%), as
      were the predicted CYP2D6 metabolic phenotypes (>97%). We conclude that CYP2D6
      genotypes obtained from FFPETs accurately represent the patient's CYP2D6
      metabolic phenotype. 

PMID- 23958739
TI  - Time to reach a new equilibrium after changes in PEEP in acute respiratory
      distress syndrome patients.

PMID- 23958738
TI  - Harmonizing international trials of early goal-directed resuscitation for severe
      sepsis and septic shock: methodology of ProCESS, ARISE, and ProMISe.
AB  - PURPOSE: To describe and compare the design of three independent but
      collaborating multicenter trials of early goal-directed resuscitation for severe
      sepsis and septic shock. METHODS: We reviewed the three current trials, one each
      in the USA (ProCESS: protocolized care for early septic shock), Australasia
      (ARISE: Australasian resuscitation in sepsis evaluation), and the UK (ProMISe:
      protocolised management in sepsis). We used the 2010 CONSORT (consolidated
      standards of reporting trials) statement and the 2008 CONSORT extension for
      trials assessing non-pharmacologic treatments to describe and compare the
      underlying rationale, commonalities, and differences. RESULTS: All three trials
      conform to CONSORT guidelines, address the same fundamental questions, and share
      key design elements. Each trial is a patient-level, equal-randomized, parallel
      group superiority trial that seeks to enroll emergency department patients with
      inclusion criteria that are consistent with the original early goal-directed
      therapy (EGDT) trial (suspected or confirmed infection, two or more systemic
      inflammatory response syndrome criteria, and refractory hypotension or elevated
      lactate), is powered to detect a 6-8 % absolute mortality reduction (hospital or
      90-day), and uses trained teams to deliver EGDT. Design differences appear to
      primarily be driven by between-country variation in health care context. The main
      difference between the trials is the inclusion of a third, alternative
      resuscitation strategy arm in ProCESS. CONCLUSIONS: Harmonization of study design
      and methods between severe sepsis trials is feasible and may facilitate pooling
      of data on completion of the trials.

PMID- 23958740
TI  - The new trials of early goal-directed  resuscitation: three-part harmony  or
      disharmony?

PMID- 23958742
TI  - Claiming positive results from negative trials: a cause for concern in randomized
      controlled trial research--author's reply.

PMID- 23958741
TI  - The course of disability before and after a serious fall injury.
AB  - IMPORTANCE: Although a serious fall injury is often a devastating event, little
      is known about the course of disability (ie, functional trajectories) before a
      serious fall injury or the relationship between these trajectories and those that
      follow the fall. OBJECTIVES: To identify distinct sets of functional trajectories
      in the year immediately before and after a serious fall injury, to evaluate the
      relationship between the prefall and postfall trajectories, and to determine
      whether these results differed based on the type of injury. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective cohort study conducted in greater New Haven,
      Connecticut, from March 16, 1998, to June 30, 2012, in 754 community-living
      persons aged 70 years or older who were initially nondisabled in their basic
      activities of daily living. Of the 130 participants who subsequently sustained a
      serious fall injury, 62 had a hip fracture and 68 had another fall-related injury
      leading to hospitalization. MAIN OUTCOMES AND MEASURES: Functional trajectories,
      based on 13 basic, instrumental, and mobility activities assessed during monthly
      interviews, were identified in the year before and the year after the serious
      fall injury. RESULTS: Before the fall, 5 distinct trajectories were identified:
      no disability in 16 participants (12.3%), mild disability in 34 (26.2%), moderate
      disability in 34 (26.2%), progressive disability in 23 (17.7%), and severe
      disability in 23 (17.7%). After the fall, 4 distinct trajectories were
      identified: rapid recovery in 12 participants (9.2%), gradual recovery in 35
      (26.9%), little recovery in 26 (20.0%), and no recovery in 57 (43.8%). For both
      hip fractures and other serious fall injuries, the probabilities of the postfall
      trajectories were greatly influenced by the prefall trajectories, such that rapid
      recovery was observed only among persons who had no disability or mild
      disability, and a substantive recovery, defined as rapid or gradual, was highly
      unlikely among those who had progressive or severe disability. The postfall
      trajectories were consistently worse for hip fractures than for the other serious
      injuries. CONCLUSIONS AND RELEVANCE: The functional trajectories before and after
      a serious fall injury are quite varied but highly interconnected, suggesting that
      the likelihood of recovery is greatly constrained by the prefall trajectory.

PMID- 23958743
TI  - Catalytic enantioselective Amadori-Heyns rearrangement of racemic alpha-hydroxy
      ketones with arylamines: synthesis of optically active alpha-arylamino ketones.
AB  - A novel synthesis of optically active alpha-arylamino ketones through an
      organocatalytic enantioselective Amadori-Heyns rearrangement is described. 

PMID- 23958745
TI  - Molecular pathways: protein methyltransferases in cancer.
AB  - The protein methyltransferases (PMT) constitute a large and important class of
      enzymes that catalyze site-specific methylation of lysine or arginine residues on
      histones and other proteins. Site-specific histone methylation is a critical
      component of chromatin regulation of gene transcription-a pathway that is often
      genetically altered in human cancers. Oncogenic alterations (e.g., mutations,
      chromosomal translocations, and others) of PMTs, or of associated proteins, have
      been found to confer unique dependencies of cancer cells on the activity of
      specific PMTs. Examples of potent, selective small-molecule inhibitors of
      specific PMTs are reviewed that have been shown to kill cancers cells bearing
      such oncogenic alterations, while having minimal effect on proliferation of
      nonaltered cells. Selective inhibitors of the PMTs, DOT1L and EZH2, have entered
      phase I clinical studies and additional examples of selective PMT inhibitors are
      likely to enter the clinic soon. The current state of efforts toward clinical
      testing of selective PMT inhibitors as personalized cancer therapeutics is
      reviewed here.

PMID- 23958746
TI  - Recovery and local-variation of Dirac cones in oxygen-intercalated graphene on
      Ru(0001) studied using scanning tunneling microscopy and spectroscopy.
AB  - Methods to decouple epitaxial graphene from metal substrates have been
      extensively studied, with anticipation of observing unperturbed Dirac cone
      properties, but its local electronic structures were rarely studied. Here, we
      investigated the local variations of Dirac cones recovered using oxygen
      intercalation applied to epitaxial graphene on Ru(0001) using scanning tunneling
      microscopy and spectroscopy (STM and STS). New V-shaped features, which appear in
      the STS data at the oxygen-intercalated graphene regions, are attributed to the
      signatures of recovered Dirac cones. The Dirac point energy was observed at 0.48
      eV below the Fermi level, different from previous photoemission results because
      of different oxygen coverages. The observed spatial variations of Dirac point
      energy were explained by the weakly protruding network structures caused by a
      small net strain in graphene. Our study shows that oxygen-intercalated graphene
      provides an excellent platform for further graphene research at the nano-meter
      scale with unperturbed Dirac cones. 

PMID- 23958744
TI  - Molecular pathways: adipose inflammation as a mediator of obesity-associated
      cancer.
AB  - The increasing rate of obesity worldwide is predicted to be associated with a
      surge in diseases. Notably, obesity has been linked to approximately 20% of
      cancer cases in the United States; obesity is associated with both increased risk
      and worse outcomes after diagnosis. Altered levels of circulating factors are
      strongly implicated, including insulin, insulin-like growth factor 1, leptin,
      adiponectin, and interleukin-6 (IL-6). In addition, increasing attention has
      focused on the consequences of local adipose inflammation. Inflammatory foci
      characterized by crown-like structures consisting of dead adipocytes encircled by
      macrophages occur in white adipose depots, including the breast tissue, of most
      overweight and obese women. Saturated fatty acids, released as a consequence of
      obesity-associated lipolysis, induce macrophage activation via Toll-like receptor
      4, thereby stimulating NF-kappaB signaling. This, in turn, activates
      transcription of proinflammatory genes including COX-2, IL-6, IL-1beta, and
      TNFalpha. Elevated levels of proinflammatory mediators cause both local and
      systemic effects. Of particular relevance with regard to breast cancer is
      increased transcription of the CYP19 gene encoding aromatase, the rate-limiting
      enzyme for estrogen synthesis. Notably, this obesity-inflammation-aromatase axis
      provides a plausible explanation for increased rates of postmenopausal, hormone
      receptor-positive breast cancer associated with obesity and hence may offer
      targets for interventions to attenuate risk or improve prognosis. Potential
      approaches include weight reduction, exercise, and suppression of obesity-driven
      signaling pathways using pharmaceutical or dietary agents. A key future goal is
      to identify biomarkers that accurately report adipose inflammation, both for
      identification of at-risk individuals and to assess the efficacy of
      interventions. Clin Cancer Res; 19(22); 6074-83. (c)2013 AACR. 

PMID- 23958747
TI  - A novel, highly sensitive method for assessing gap junctional coupling.
AB  - To assess gap junctional intercellular communication we have developed a tracer
      based methodology which is both highly sensitive and potentially adaptable for in
      vivo measurements. We found that injection of serotonin revealed significantly
      more intercellular communication than that injection of the most permeant
      synthetic tracer currently in use, neurobiotin. Furthermore, mechanical tracer
      loading steps can be replaced by transfection with human serotonin transporter
      and the inclusion of serotonin in the medium. Tracer and transporter are detected
      using immunocytochemical techniques and the presence of cells that are tracer
      positive but transporter-negative indicates junctional communication. Tracer
      loading in vivo using transgenesis, electroporation or viral transduction to
      direct expression of transporter should be more easily accomplished than with
      mechanical loading methods. 

PMID- 23958748
TI  - Superparamagnetic beads for estimation of spinal subarachnoid space permeability
      in rats.
AB  - BACKGROUND: Human spinal pathological processes have been linked to a loss of
      spinal subarachnoid space (SSAS) permeability, which has therefore become a
      target for therapy. Hence, it has become important to measure SSAS patency in rat
      models of these human disorders. NEW METHOD: The estimation of in vivo rat SSAS
      patency is described by quantifying passage of streptavidin-covered
      superparamagnetic beads (SPMB) in cerebrospinal fluid (CSF). Beads are injected
      into the cisterna magna and recovered at spinal level L2. They are then coated
      with biotynilated horseradish peroxidase for enzymatically based colorimetric
      measurement, after removal of bloody CSF to avoid interference with the
      colorimetric readings. The procedure was tested in intact rats and in rats 24 h
      after T9 laminectomy. Residual beads in SSAS were viewed by histology. RESULTS:
      Average bead recovery from intact rats was 6.4% of amount initially administered,
      in a mean CSF volume of 126 MUL; in laminectomized rats, it was 1%, in a mean CSF
      volume of 39.2 MUL. COMPARISON WITH EXISTING METHOD(S): Unlike in vivo imaging
      techniques, such as myelography (used here to validate our method) and near
      infrared fluorescence technology for qualitative rat SSAS patency viewing, our
      SPMB-based method allows for an in vivo quantitative estimation of the
      permeability of this space. CONCLUSIONS: A novel method has been established to
      reliably determine SSAS permeability in rats. The method is reproducible and has
      the required sensitivity to detect an 84.4% reduction in bead recovery, as seen
      in laminectomized rats compared to intact animals.

PMID- 23958749
TI  - Thresholds in fMRI studies: reliable for single subjects?
AB  - Many studies have investigated test-retest reliability of active voxel
      classification for fMRI, which is increasingly important for emerging clinical
      applications. The implicit impact of voxel-wise thresholding on this type of
      reliability has previously been under-appreciated. This has had two detrimental
      effects: (1) reliability studies use different fixed thresholds, making
      comparison of results is challenging; (2) typical studies do not assess
      reliability at the individual level, which could provide information for
      selecting activation thresholds. To show the limitations of traditional fixed
      threshold approaches, we investigated the threshold dependence of fMRI
      reliability measures, with the goal of developing an automated threshold
      selection routine. For this purpose, we demonstrated threshold dependence of both
      novel (ROC-reliability or ROC-r) and established (Rombouts overlap or RR)
      reliability measures. Both methods rely minimally on statistical assumptions, and
      provide a data-driven summary of the threshold-reliability relationship. We
      applied these methods to data from eight subjects performing a simple finger
      tapping task across repeated fMRI sessions. We showed that the reliability
      measures varied dramatically with threshold. This variation depended strongly on
      the individual tested. Finally, we demonstrated novel procedures using ROC-r and
      overlap analysis to optimize thresholds on a case-by-case basis. Ultimately, a
      method to determine robust individual-level activation maps represents a critical
      advance for fMRI as a diagnostic tool. 

PMID- 23958750
TI  - RNAlater facilitates microdissection of sensory cell-enriched samples from the
      mouse cochlea for transcriptional analyses.
AB  - Molecular analyses of cochlear pathology rely on the acquisition of high-quality
      cochlear samples. For small rodents, isolating sensory cell-enriched samples with
      well-preserved RNA integrity for transcriptional analyses poses a significant
      challenge. Here, we report a microdissection technique for isolating sensory cell
      enriched samples from the cochlea. We found that treating the tissue with
      RNAlater, a RNA preservation medium, alters the physical properties of the tissue
      and facilitates the dissection. Unlike previous samples that have been isolated
      from the sensory epithelium, our samples contain defined cell populations that
      have a consistent ratio of sensory cells to supporting cells. Importantly, the
      RNA components were well preserved. With this microdissection method, we
      collected three types of samples: sensory cell-enriched, outer hair cell
      enriched, and inner hair cell-enriched. To demonstrate the feasibility of the
      method, we screened multiple reference genes in the sensory cell-enriched samples
      and identified stable genes in noise-traumatized cochleae. The method described
      here balances the need for both quality and purity of sensory cells and also
      circumvents many limitations of the currently available techniques for collecting
      cochlear tissues. With our approach, the collected samples can be used in diverse
      downstream analyses, including qRT-PCR, microarray, and RNA sequencing. 

PMID- 23958751
TI  - Are quantitative and clinical measures of bradykinesia related in advanced
      Parkinson's disease?
AB  - INTRODUCTION: Bradykinesia is usually assessed using clinical rating scales. In
      some circumstances, a laboratory assessment of bradykinesia using tools of higher
      resolution is required. One task often used for the evaluation of bradykinesia is
      a rapid alternating movement (RAM) of the hand. However, the relationship between
      clinical scores of bradykinesia and the properties of a RAM task assessed
      quantitatively has yet to be determined. OBJECTIVE: Identify which of the
      commonly used properties of a RAM task are related to a clinical score of
      bradykinesia and assess the strength of this relationship. METHODS: Nineteen
      patients with idiopathic Parkinson's disease were tested ON and OFF medication.
      They performed three trials of the RAM task and were assessed clinically using
      the Unified Parkinson's disease rating scale in each condition and with each
      hand. RESULTS: A statistically significant correlation was observed between the
      clinical score of bradykinesia and two of the properties of the RAM task; namely
      mean and maximal velocity. COMPARISON WITH EXISTING METHODS: These results
      indicate that a RAM task does provide a measure of bradykinesia but it is only
      moderately correlated to a clinical rating of this motor symptom. CONCLUSION: We
      propose that the results from the RAM task represent a measure of "core
      bradykinesia" while a clinical evaluation represents a composite score of
      bradykinesia, movement amplitude and motor coordination.

PMID- 23958752
TI  - Polyethylene glycol as an alternative polymer solvent for nanoparticle
      preparation.
AB  - Solvent toxicity is one of the major drawbacks in the preparation of polymeric
      nanoparticles today. Here, polyethylene glycols (PEGs) are proposed as non-toxic
      solvents for the preparation of polymeric nanoparticles. Based on a preparation
      process similar to the solvent displacement technique, several process parameters
      were examined for their effects on the properties of the prepared nanoparticles
      by this method to achieve the optimum preparation conditions. The investigated
      parameters included polymer type and concentration, volume and temperature of the
      dispersing phase, methods of dispersing the solvent phase into the non-solvent
      phase, duration and speed of stirring and washing by dialysis. Ammonio
      methacrylate copolymer (Eudragit RL), poly-lactide-co-glycolide (PLGA), and PEG
      PLGA were found to be successful polymer candidates for the preparation of
      nanoparticles by this method. Nanoparticles with diameters ranging from 80 to 400
      nm can be obtained. The encapsulation efficiencies of bovine serum albumin, and
      lysozyme as model proteins were ranging from 7.3+/-2.2% to 69.3+/-1.8% depending
      on the strength of polymer-protein interaction. Biological assays confirmed a
      full lysozyme activity after the preparation process. PEG proved to be a suitable
      non-toxic solvent for the preparation of polymeric protein-loaded nanoparticles,
      maintaining the integrity of protein.

PMID- 23958753
TI  - Development of a novel antimicrobial seaweed extract-based hydrogel wound
      dressing.
AB  - The objective of this study was to develop a novel antimicrobial seaweed wound
      dressing. The seaweed extract was active against nine clinically-relevant wound
      pathogens. A hydrogel formulation was prepared using polyvinyl alcohol (PVA) and
      polyvinylpyrrolidone (PVP), followed by addition of 1% seaweed extract. The
      antimicrobial properties of the novel dressing were tested using agar diffusion
      assays, with release-profiles examined using gel leaching and gel transfer
      assays. The dressing was found to be effective against the same microbial strains
      as the seaweed extract, with similar efficacy to the commonly used silver-based
      dressing, Acticoat((r)). Antimicrobial release-profile assays revealed that the
      dressing was effective in inhibiting 70-90% of the bacterial population within
      the first 30 min, followed by a long, sustained released up to 97 h, without
      leaving a residue following five subsequent transfers of the dressing.
      Antimicrobial activity was stable for up to 6 months of storage at 4  degrees C,
      but activity was reduced slightly after 15 weeks. Following autoclave
      sterilization, the dressing displayed a slower release profile compared to a non
      autoclaved counterpart. Hence, the seaweed dressing may have commercial
      applications, potentially competing with silver-based dressings at a lower cost
      per-application. This is the first report of development of a seaweed-based
      antimicrobial dressing.

PMID- 23958754
TI  - Inhibitory effects of cultured Dendrobium tosaense on atopic dermatitis murine
      model.
AB  - Dendrobium tosaense is one of the most valuable Chinese medicines and well
      developed health food. Atopic dermatitis (AD) is a chronic skin disease that
      occurs mainly in childhood. The pathogenesis of atopic dermatitis had been
      studied in BALB/c mice modeling by skin-inoculated ovalbumin (OVA) with 2,4,6
      trinitro-1-chrolobenzene (TNCB). These mice exhibit features of chronic
      dermatitis, including skin rash, mast cells infiltration, and elevated serum anti
      OVA specific IgE and cytokines modulation. In this study, a standardized ethyl
      acetate extract of D. tosaense (DtE) was used to protect these mice from the
      OVA/TNCB-induced skin lesions of atopic dermatitis. The results indicated an
      increased population of natural T regulatory cell was accompanied by
      immunosuppression in cytokine profiles and anti-OVA IgE level to significantly
      reduce Th2 polarization. Finally, toluidine blue staining indicated mast cell
      infiltration and degranulation was reduced in skin lesion. Our results were shed
      light on the usage of D. tosaense in AD. 

PMID- 23958756
TI  - Functional mitral regurgitation after a first non-ST segment elevation acute
      coronary syndrome: very-long-term follow-up, prognosis and contribution to left
      ventricular enlargement and atrial fibrillation development.
AB  - OBJECTIVE: To assess the relationship between functional mitral regurgitation
      (MR) after a non-ST segment elevation acute coronary syndrome (NSTSEACS) and long
      term prognosis, ventricular remodelling and further development of atrial
      fibrillation (AF), since functional MR is common after myocardial infarction.
      DESIGN AND SETTING: Prospective cohort study conducted in a tertiary referral
      centre. PATIENTS: We prospectively studied 237 patients consecutively discharged
      in New York Heart Association class I-II (74% men; mean age 66.1 years) after a
      first NSTSEACS. All underwent an ECG the first week after admission and were
      echocardiographically and clinically followed-up (median 6.95 years). RESULTS: MR
      was detected in 95 cases (40.1%) and became an independent risk factor for the
      development of heart failure (HF) and major adverse cardiovascular events (MACE)
      (per MR degree, HRHF 1.71, 95% CI 1.138 to 2.588, p=0.01; HRMACE 1.49, 95% CI
      1.158 to 1.921, p=0.002). Left ventricular diastolic (grade I 12.7+/-40.7; grade
      II 26.8+/-12.4; grade III 46.3+/-50.9 mL, p=0.01) and systolic (grade I 10.4+/
      37.3; grade II 10.12+/-12.7; grade III 36.8+/-46.0 mL, p=0.02) mean volumes were
      higher after follow-up in patients with MR, in proportion to the initial degree
      of MR. In the rhythm analysis (126 patients; previously excluding those with any
      history of AF) during follow-up, 11.4% of patients with degree I MR, 14.3% with
      degree II MR and 75% with degree III MR developed AF, while only 5.1% of those
      with degree 0 developed AF, p<0.001. CONCLUSIONS: MR is common after an NSTSEACS.
      The presence and greater degree of MR confers a worse long-term prognosis after a
      first NSTSEACS. This can in part be explained by increased negative ventricular
      remodelling and increased occurrence of AF.

PMID- 23958757
TI  - Drug-eluting balloon for instent restenosis--the author's reply.

PMID- 23958758
TI  - A response to a misrepresentation of the STEMI guidelines: the response.

PMID- 23958759
TI  - Preserved stroke volume late after tetralogy repair, despite severe right
      ventricular dilatation--the author's reply.

PMID- 23958760
TI  - Preserved stroke volume late after tetralogy repair, despite severe right
      ventricular dilatation.

PMID- 23958761
TI  - Effects of quaternary ammonium chain length on antibacterial bonding agents.
AB  - The objectives of this study were to synthesize new quaternary ammonium
      methacrylates (QAMs) with systematically varied alkyl chain lengths (CL) and to
      investigate, for the first time, the CL effects on antibacterial efficacy,
      cytotoxicity, and dentin bond strength of bonding agents. QAMs were synthesized
      with CL of 3 to 18 and incorporated into Scotchbond Multi-Purpose (SBMP) bonding
      agent. The cured resins were inoculated with Streptococcus mutans. Bacterial
      early attachment was investigated at 4 hrs. Biofilm colony-forming units (CFU)
      were measured after 2 days. With CL increasing from 3 to 16, the minimum
      inhibitory concentration and minimum bactericidal concentration were decreased by
      5 orders of magnitude. Incorporating QAMs into SBMP reduced bacterial early
      attachment, with the least colonization at CL = 16. Biofilm CFU for CL = 16 was 4
      log lower than SBMP control (p < .05). All groups had similar dentin bond
      strengths (p > .1). The new antibacterial materials had fibroblast/odontoblast
      viability similar to that of commercial controls. In conclusion, increasing the
      chain length of new QAMs in bonding agents greatly increased the antibacterial
      efficacy. A reduction in Streptococcus mutans biofilm CFU by 4 log could be
      achieved, without compromising bond strength and cytotoxicity. New QAM-containing
      bonding agents are promising for a wide range of restorations to inhibit
      biofilms. 

PMID- 23958762
TI  - LAMB3 mutations causing autosomal-dominant amelogenesis imperfecta.
AB  - Amelogenesis imperfecta (AI) can be either isolated or part of a larger syndrome.
      Junctional epidermolysis bullosa (JEB) is a collection of autosomal-recessive
      disorders featuring AI associated with skin fragility and other symptoms. JEB is
      a recessive syndrome usually caused by mutations in both alleles of COL17A1,
      LAMA3, LAMB3, or LAMC2. In rare cases, heterozygous carriers in JEB kindreds
      display enamel malformations in the absence of skin fragility (isolated AI). We
      recruited two kindreds with autosomal-dominant amelogenesis imperfecta (ADAI)
      characterized by generalized severe enamel hypoplasia with deep linear grooves
      and pits. Whole-exome sequencing of both probands identified novel heterozygous
      mutations in the last exon of LAMB3 that likely truncated the protein. The
      mutations perfectly segregated with the enamel defects in both families. In
      Family 1, an 8-bp deletion (c.3446_3453del GACTGGAG) shifted the reading frame
      (p.Gly 1149Glufs*8). In Family 2, a single nucleotide substitution (c.C3431A)
      generated an in-frame translation termination codon (p.Ser1144*). We conclude
      that enamel formation is particularly sensitive to defects in
      hemidesmosome/basement-membrane complexes and that syndromic and non-syndromic
      forms of AI can be etiologically related. 

PMID- 23958763
TI  - Bis-enoxacin inhibits bone resorption and orthodontic tooth movement.
AB  - Enoxacin inhibits binding between the B-subunit of vacuolar H(+)-ATPase (V
      ATPase) and microfilaments, and also between osteoclast formation and bone
      resorption in vitro. We hypothesized that a bisphosphonate derivative of
      enoxacin, bis-enoxacin (BE), which was previously studied as a bone-directed
      antibiotic, might have similar activities. BE shared a number of characteristics
      with enoxacin: It blocked binding between the recombinant B-subunit and
      microfilaments and inhibited osteoclastogenesis in cell culture with IC50s of
      about 10 uM in each case. BE did not alter the relative expression levels of
      various osteoclast-specific proteins. Even though tartrate-resistant acid
      phosphatase 5b was expressed, proteolytic activation of the latent pro-enzyme was
      inhibited. However, unlike enoxacin, BE stimulated caspase-3 activity. BE bound
      to bone slices and inhibited bone resorption by osteoclasts on BE-coated bone
      slices in cell culture. BE reduced the amount of orthodontic tooth movement
      achieved in rats after 28 days. Analysis of these data suggests that BE is a
      novel anti-resorptive molecule that is active both in vitro and in vivo and may
      have clinical uses. ABBREVIATIONS: BE, bis-enoxacin; V-ATPase, vacuolar H(+)
      ATPase; TRAP, tartrate-resistant acid phosphatase; alphaMEM D10, minimal
      essential media, alpha modification with 10% fetal bovine serum; SDS-PAGE, sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis; RANKL, receptor activator of
      nuclear factor kappa B-ligand; NFATc1, nuclear factor of activated T-cells; ADAM,
      a disintegrin and metalloprotease domain; OTM, orthodontic tooth movement.

PMID- 23958764
TI  - Probiotic administration in early life, atopy, and asthma: a meta-analysis of
      clinical trials.
AB  - BACKGROUND AND OBJECTIVE: Probiotics may reduce the risk of atopy and asthma in
      children. However, results from clinical trials have been conflicting, and
      several of them may have been underpowered. We performed a meta-analysis of
      randomized, placebo-controlled trials to assess the effects of probiotic
      supplementation on atopic sensitization and asthma/wheeze prevention in children.
      METHODS: Random-effects models were used to calculate pooled risk estimates. Meta
      regression was conducted to examine the effect of potential factors on probiotics
      efficacy. RESULTS: Probiotics were effective in reducing total immunoglobulin E
      (IgE) (mean reduction: -7.59 U/mL [95% confidence interval (CI): -14.96 to 
      0.22]; P = .044). Meta-regression showed that the reduction in IgE was more
      pronounced with longer follow-up. Probiotics significantly reduced the risk of
      atopic sensitization when administered prenatally (relative risk: 0.88 [95% CI:
      0.78 to 0.99]; P = .035 for positive result on the skin prick test and/or
      elevated specific IgE to common allergens) and postnatally (relative risk: 0.86
      [95% CI: 0.75 to 0.98]; P = .027 for positive result on skin prick test).
      Administration of Lactobacillus acidophilus, compared with other strains, was
      associated with an increased risk of atopic sensitization (P = .002). Probiotics
      did not significantly reduce asthma/wheeze (relative risk: 0.96 [95% CI: 0.85 to
      1.07]). CONCLUSIONS: Prenatal and/or early-life probiotic administration reduces
      the risk of atopic sensitization and decreases the total IgE level in children
      but may not reduce the risk of asthma/wheeze. Follow-up duration and strain
      significantly modified these effects. Future trials for asthma prevention should
      carefully select probiotic strain and consider longer follow-up.

PMID- 23958766
TI  - "Fat letters" in public schools: public health versus pride.

PMID- 23958765
TI  - Bisphenol A and chronic disease risk factors in US children.
AB  - OBJECTIVE: To evaluate the relationship between urinary bisphenol A (BPA) levels
      and measures of adiposity and chronic disease risk factors for a nationally
      representative US pediatric sample. METHODS: We used the NHANES 2003-2010 to
      evaluate cross-sectional associations between urinary BPA and multiple measures
      of adiposity, cholesterol, insulin, and glucose for children aged 6 to 18 years,
      adjusting for relevant covariates (eg, demographics, urine creatinine, tobacco
      exposure, and soda consumption). RESULTS: We found a higher odds of obesity (BMI
      >=95th percentile) with increasing quartiles of BPA for quartiles 2 vs 1 (odds
      ratio [OR] 1.74, 95% confidence interval [CI] 1.17-2.60, P = .008), 3 vs 1 (OR
      1.64, 95% CI 1.09-2.47, P = .02), and 4 vs 1 (OR 2.01, 95% CI 1.36-2.98, P =
      .001). We also found a higher odds of having an abnormal waist circumference-to
      height ratio (quartiles 2 vs 1 [OR 1.37, 95% CI 0.98-1.93, P = .07], 3 vs 1 [OR
      1.41, 95% CI 1.07-1.87, P = .02], and 4 vs 1 [OR 1.55, 95% CI 1.12-2.15, P =
      .01]). We did not find significant associations of BPA with any other chronic
      disease risk factors. CONCLUSIONS: Higher levels of urinary BPA were associated
      with a higher odds of obesity (BMI >95%) and abnormal waist circumference-to
      height ratio. Longitudinal analyses are needed to elucidate temporal
      relationships between BPA exposure and the development of obesity and chronic
      disease risk factors in children.

PMID- 23958767
TI  - A young adult Jehovah's Witness with severe anemia.
AB  - Two of the most ethically complex situations in pediatrics are those involving
      families whose religious beliefs preclude the provision of life-sustaining
      treatment and those involving young adults who have reached the age of legal
      majority and who face decisions about life-sustaining treatment. This month's
      "Ethics Rounds" presents a case in which these 2 complexities overlapped. An 18
      year-old Jehovah's Witness with sickle cell disease has life-threatening anemia.
      She is going into heart failure. Her doctors urgently recommend blood
      transfusions. The young woman and her family adamantly refuse. Should the doctors
      let her die? Is there any alternative? 

PMID- 23958768
TI  - Use of a computerized decision aid for ADHD diagnosis: a randomized controlled
      trial.
AB  - OBJECTIVE: To determine if implementing attention-deficit/hyperactivity disorder
      (ADHD) diagnosis and treatment guidelines in a clinical decision support system
      would result in better care, including higher rates of adherence to clinical care
      guidelines. METHODS: We conducted a cluster randomized controlled trial in which
      we compared diagnosis and management of ADHD in 6- to 12-year-olds after
      implementation of a computer decision support system in 4 practices. RESULTS:
      Eighty-four charts were reviewed. In the control group, the use of structured
      diagnostic assessments dropped from 50% in the baseline period to 38% in the
      intervention period. In the intervention group, however, it rose from 60% to 81%.
      This difference was statistically significant, even after controlling for age,
      gender, and race (odds ratio of structured diagnostic assessment in intervention
      group versus control group = 8.0, 95% confidence interval 1.6-40.6). Significant
      differences were also seen in the number of ADHD core symptoms noted at the time
      of diagnosis. Our study was not powered to detect changes in care and management,
      but the percent of patients who had documented medication adjustments, mental
      health referrals, and visits to mental health specialists were higher in the
      intervention group than the control. CONCLUSIONS: The introduction of a clinical
      decision support module resulted in higher quality of care with respect to ADHD
      diagnosis including a prospect for higher quality of ADHD management in children.
      Future work will examine how to further develop the ADHD module and add support
      for other chronic conditions.

PMID- 23958769
TI  - Imperforate hymen presenting as chronic low back pain.
AB  - Imperforate hymen in an adolescent usually presents with cyclic abdominal pain or
      with pelvic mass associated with primary amenorrhea. We present a 13-year-old
      girl with chronic lower back pain of 6 months' duration as the only complaint. On
      physical examination, multiple trigger points were detected in the quadratus
      lumborum and gluteus medius muscles bilaterally. Abdominal ultrasound revealed
      hematometrocolpos secondary to an imperforate hymen. Hymenectomy was performed,
      with complete resolution of the back pain. Myofascial pain syndrome with a
      viscerosomatic reflex is a possible explanation for the clinical presentation of
      our patient. 

PMID- 23958770
TI  - Pediatrician identification of Latino children at risk for autism spectrum
      disorder.
AB  - BACKGROUND AND OBJECTIVES: Latino-white disparities in age at autism spectrum
      disorder (ASD) diagnosis may be modified by primary care pediatrician (PCP)
      practices and beliefs. The objectives of this study were to assess ASD and
      developmental screening practices, attitudes toward ASD identification in Latino
      children, and barriers to ASD identification for Latino children, in a sample of
      267 California PCPs. METHODS: In mail-based PCP survey, we assessed rates of
      bilingual general developmental and ASD screening, perceptions of parent ASD
      knowledge in Latino and white families, reports of difficulty assessing for ASDs
      in Latino and white children, and perceptions of barriers to early ASD
      identification for Latinos. RESULTS: Although 81% of PCPs offered some form of
      developmental screening, 29% of PCPs offered Spanish ASD screening per American
      Academy of Pediatrics guidelines, and only 10% offered both Spanish general
      developmental and Spanish ASD screening per American Academy of Pediatrics
      guidelines. Most PCPs thought that Latino (English and Spanish primary family
      language) parents were less knowledgeable about ASDs than white parents. PCPs had
      more difficulty assessing ASD risk for Latino children with Spanish primary
      family language than for white children, even when the PCP conducted recommended
      ASD screening or had >25% Latino patients. The most frequent barrier to ASD
      identification in Latinos was access to developmental specialists. CONCLUSIONS:
      Multiple factors in the primary care setting may contribute to delayed ASD
      identification for Latinos. Promoting language-appropriate screening,
      disseminating culturally appropriate ASD materials to Latino families, improving
      the specialist workforce, and providing PCP support in screening and referral of
      Latino children may be important ways to reduce racial and ethnic differences in
      care.

PMID- 23958771
TI  - Enriched environments and motor outcomes in cerebral palsy: systematic review and
      meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: Neuroplasticity evidence from animals favors an early
      enriched environment for promoting optimal brain injury recovery. In infants,
      systematic reviews show environmental enrichment (EE) improves cognitive outcomes
      but the effect on motor skills is less understood. The objective of this review
      was to appraise the effectiveness evidence about EE for improving the motor
      outcomes of infants at high risk of cerebral palsy (CP). METHODS: A systematic
      review was conducted. Cochrane Central Register of Controlled Trials (PubMed),
      Cumulative Index to Nursing and Allied Health Literature, Education Resource
      Information Center, SocINDEX, and PsycINFO databases were searched for literature
      meeting inclusion criteria: randomized controlled trials; high risk of /diagnosis
      of CP; >25% participants <=2 years; parent or infant interventions postdischarge;
      and motor outcomes reported. Data were extracted using the Cochrane protocol
      regarding participants, intervention characteristics, and outcomes.
      Methodological quality was assessed using risk of bias assessment and GRADE.
      RESULTS: A total of 226 studies were identified. After removing duplicates and
      unrelated studies, 16 full-text articles were reviewed, of which 7 studies met
      inclusion criteria. The risk of bias varied between studies with the more recent
      studies demonstrating the lowest risk. Enrichment interventions varied in type
      and focus, making comparisons difficult. A meta-analysis was conducted of studies
      that compared enrichment to standard care (n = 5), and totaled 150 infants. A
      small positive effect for enrichment was found; standardized mean difference 0.39
      (95% confidence interval 0.05-0.72; I(2) = 3%; P = .02) CONCLUSIONS: EE looks
      promising for CP, and therefore high-quality studies with well-defined EE
      strategies are urgently required.

PMID- 23958773
TI  - Diagnosis and outcome of SCN4A-related severe neonatal episodic laryngospasm
      (SNEL): 2 new cases.
AB  - Mutations of SCN4A encoding the skeletal muscle sodium channel Nav 1.4 cause
      several types of disease, including sodium channel myotonias. The latter may be
      responsible for neonatal symptoms, including severe neonatal episodic
      laryngospasm (SNEL). Establishing the diagnosis of SCN4A-related SNEL early in
      the neonatal period is crucial because treatment is available that can reduce
      laryngospasm and improve vital and cerebral outcome. We report 2 new unrelated
      French patients who presented with SNEL. The first patient was initially
      diagnosed with laryngomalacia and underwent laryngeal surgery in the neonatal
      period before being diagnosed with myotonia at 14 months of age. The episodes of
      laryngospasm disappeared spontaneously, although occasional circumstances such as
      cold exposure could trigger laryngeal reactions; in addition, he developed
      myotonia corresponding to an adult myotonia permanens phenotype. This patient is
      now 24 years old and leading a normal life. The second patient was initially
      diagnosed with gastroesophageal reflux, then SNEL; his condition improved with
      carbamazepine treatment, and he is now 6 months old. The diagnostic sequence in
      both patients was the same: first, severe episodic apneic attacks necessitating
      hospitalization occurring in the first week of life; second, observation of
      muscle hypertrophy and peripheral hypertonia with a clear myotonic pattern on
      electromyogram (at 14 and 3 months of age, respectively); third, genetic testing
      revealing de novo SCN4A G1306E mutation. Both patients have had good therapeutic
      response to sodium channel blockers (carbamazepine or mexiletine). 

PMID- 23958772
TI  - Urinary phthalates and increased insulin resistance in adolescents.
AB  - BACKGROUND: Di-2-ethylhexylphthalate (DEHP) is an environmental chemical commonly
      found in processed foods. Phthalate exposures, in particular to DEHP, have been
      associated with insulin resistance in adults, but have not been studied in
      adolescents. METHODS: Using cross-sectional data from 766 fasting 12- to 19-year
      olds in the 2003-2008 NHANES, we examined associations of phthalate metabolites
      with continuous and categorical measures of homeostatic model assessment of
      insulin resistance (HOMA-IR). RESULTS: Controlling for demographic and behavioral
      factors, diet, continuous age, BMI category, and urinary creatinine, for each log
      (roughly threefold) increase in DEHP metabolites, a 0.27 increase (95% confidence
      interval 0.14-0.40; P < .001) in HOMA-IR was identified. Compared with the first
      tertile of DEHP metabolite in the study population (14.5% insulin resistant), the
      third tertile had 21.6% prevalence (95% confidence interval 17.2%-26.0%; P =
      .02). Associations persisted despite controlling for bisphenol A, another
      endocrine-disrupting chemical commonly found in foods, and HOMA-IR and insulin
      resistance were not significantly associated with metabolites of lower molecular
      weight phthalates commonly found in cosmetics and other personal care products.
      CONCLUSIONS: Urinary DEHP concentrations were associated with increased insulin
      resistance in this cross-sectional study of adolescents. This study cannot rule
      out the possibility that insulin-resistant children ingest food with higher
      phthalate content, or that insulin-resistant children excrete more DEHP.

PMID- 23958774
TI  - Rapid implementation of evidence-based guidelines for imaging after first urinary
      tract infection.
AB  - BACKGROUND AND OBJECTIVES: The American Academy of Pediatrics published a new
      guideline for management of first urinary tract infection (UTI) in children aged
      2 to 24 months in September 2011. The imaging evaluation changed from the
      previous guideline to recommend voiding cystourethrogram (VCUG) only for patients
      with an abnormal renal and bladder ultrasound (RBUS). The objective was to
      decrease the proportion of guideline-eligible children with a normal RBUS who
      underwent VCUG from median of 92% for patients treated as inpatients and 100% for
      patients treated in the emergency department to 5% in both settings. METHODS:
      This was a quality improvement implementation study in a large academic medical
      center. Key drivers included: appropriate guideline knowledge, timely
      identification of guideline eligible patients, and effective communication with
      the community-based primary care provider. A multidisciplinary team developed and
      tested interventions. Impact was assessed with annotated run charts. Statistical
      comparisons were made with chi(2) analysis and Fisher's exact test. RESULTS: The
      proportion of children with first UTI and normal RBUS who underwent VCUG
      decreased from a median of 92% to 0% within 1 month of initiating the project
      among those hospitalized and from 100% to 40% within 4 months among those
      diagnosed in the emergency department. Rates have been sustained for 12 months
      and 8 months, respectively. Interventions using the electronic medical record and
      ordering system were most impactful. CONCLUSIONS: Rapid adoption of evidence
      based UTI care across multiple settings is achievable. Practice change occurred
      faster and to a greater magnitude in the inpatient setting compared with the
      outpatient setting.

PMID- 23958775
TI  - Implementation of critical congenital heart disease screening in Minnesota.
AB  - OBJECTIVE: To assess the level of preparedness and resources needed in Minnesota
      for the implementation of newborn screening for critical congenital heart
      diseases (CCHDs). METHODS: A cross sectional survey of all birth centers in
      Minnesota was performed to assess the capacity to deliver care essential for the
      CCHD screening program. Compliance with the screening algorithm, nursing
      workload, and cost were assessed by using a pilot program implemented in 6 normal
      newborn nurseries. RESULTS: Ninety-one of 99 eligible centers participated in the
      survey and 90 reported the ability to screen newborns in accordance with
      recommendations. Only 22 centers, with 63% of births, had access to
      echocardiography and routinely stocked prostaglandins for neonatal use. Our pilot
      study screened 7549 newborns with 6 failed screens and 1 CCHD diagnosis. Two of
      the failed screens were due to misinterpretation of the algorithm, 1 failed
      screen was not reported, and 4 failed screens were not recognized. Repeated
      screens were required for 115 newborns, with 29% of retesting due to
      misinterpretation of the algorithm. The mean nursing time required was 5.5
      minutes, and the cost was $5.10 per screen. CONCLUSIONS: In Minnesota, two-thirds
      of newborns are born in centers with resources for initial diagnosis and
      management of CCHD. Implementation of a pilot screening program demonstrated
      minimal increase in nursing workload, but identified problems with interpretation
      of the algorithm and data reporting. This pilot project suggests the need for
      simplification of the algorithm, additional training of health care providers,
      and development of a centralized reporting mechanism.

PMID- 23958776
TI  - Screening strategies for hip dysplasia: long-term outcome of a randomized
      controlled trial.
AB  - OBJECTIVE: Screening for hip dysplasia is controversial. A previous randomized
      controlled trial revealed that adding universal or selective ultrasound to
      routine clinical examination gave a nonsignificant reduction in rates of late
      presenting cases, but with higher treatment rates. This study assesses
      differences in outcome at skeletal maturity for the 3 newborn screening
      strategies in terms of radiographic markers of acetabular dysplasia and early
      degenerative change and avascular necrosis (AVN) secondary to neonatal treatment.
      METHODS: From the initial trial including 11 925 newborns, a population-based
      sample of 3935 adolescents was invited for follow-up at age 18 to 20 years. A
      standardized weight-bearing anteroposterior view was obtained. The outcomes
      evaluated were the radiographic findings of dysplasia (center-edge angle, femoral
      head extrusion-index, acetabular depth-width ratio, Sharp's angle, subjective
      evaluation of dysplasia) and degenerative change (joint-space width). Signs of
      AVN were documented. RESULTS: Of the 3935 subjects invited, 2038 (51.8%) attended
      the maturity review, of which 2011 (58.2% female patients) were included: 551,
      665, and 795 subjects from the universal, selective, and clinical groups,
      respectively. Rates per group of positive radiographic findings associated with
      dysplasia or degenerative change varied depending on radiographic marker used. No
      statistically significant differences were detected between groups. No AVN was
      seen. CONCLUSIONS: Although both selective and universal ultrasound screenings
      gave a nonsignificant reduction in rates of late cases when compared with expert
      clinical programs, we were unable to demonstrate any additional reduction in the
      rates of radiographic findings associated with acetabular dysplasia or
      degenerative change at maturity. Increased treatment rates were not associated
      with AVN.

PMID- 23958777
TI  - Urine chemical content may be a false measure of environmental exposure.

PMID- 23958778
TI  - Micropatterned dermal-epidermal regeneration matrices create functional niches
      that enhance epidermal morphogenesis.
AB  - Although tissue engineered skin substitutes have demonstrated some clinical
      success for the treatment of chronic wounds such as diabetic and venous ulcers,
      persistent graft take and stability remain concerns. Current bilayered skin
      substitutes lack the characteristic microtopography of the dermal-epidermal
      junction that gives skin enhanced mechanical stability and creates cellular
      microniches that differentially promote keratinocyte function to form skin
      appendages and enhance wound healing. We developed a novel micropatterned dermal
      epidermal regeneration matrix (MUDERM) which incorporates this complex topography
      and substantially enhances epidermal morphology. Here, we describe the use of
      this three-dimensional (3-D) in vitro culture model to systematically evaluate
      different topographical geometries and to determine their relationship to
      keratinocyte function. We identified three distinct keratinocyte functional
      niches: the proliferative niche (narrow geometries), the basement membrane
      protein synthesis niche (wide geometries) and the putative keratinocyte stem cell
      niche (narrow geometries and corners). Specifically, epidermal thickness and
      keratinocyte proliferation is significantly (p<0.05) increased in 50 and 100 MUm
      channels while laminin-332 deposition is significantly (p<0.05) increased in 400
      MUm channels compared to flat controls. Additionally, beta1(bri)p63(+)
      keratinocytes, putative keratinocyte stem cells, preferentially cluster in
      channel geometries (similar to clustering observed in native skin) compared to a
      random distribution on flats. This study identifies specific target geometries to
      enhance skin regeneration and graft performance. Furthermore, these results
      suggest the importance of MUDERM microtopography in designing the next generation
      of skin substitutes. Finally, we anticipate that 3-D organotypic cultures on
      MUDERMS will provide a novel tissue engineered skin substitute for in vitro
      investigations of skin morphogenesis, wound healing and pathology.

PMID- 23958780
TI  - Adaptable poly(ethylene glycol) microspheres capable of mixed-mode degradation.
AB  - A simple, degradable poly(ethylene glycol) (PEG) microsphere system formed from a
      water-in-water emulsion process is presented. Microsphere network degradation and
      erosion were controlled by adjusting the number of hydrolytically labile sites,
      by varying the PEG molecular weight, and by adjusting the emulsion conditions.
      Microsphere size was also controllable by adjusting the polymer formulation.
      Furthermore, it is demonstrated that alternative degradation and erosion
      mechanisms, such as proteolytic degradation, can be incorporated into PEG
      microspheres, resulting in mixed-mode degradation. Owing to the adaptability of
      this approach, it may serve as an attractive option for emerging tissue
      engineering, drug delivery and gene delivery applications.

PMID- 23958781
TI  - Self-assembly of short peptides to form hydrogels: design of building blocks,
      physical properties and technological applications.
AB  - Hydrogels are unique supramolecular solid-like assemblies composed mainly of
      water molecules that are held by molecular networks. Physical hydrogels that are
      formed by a set of non-covalent interactions to establish a well-ordered scaffold
      devoid of any chemical cross-linking are especially intriguing for various
      biotechnological and medical applications. Peptides are particularly interesting
      building blocks of physical gels because of the role of polypeptides as
      structural elements in biological systems, the extensive ability for their
      chemical and biological decoration and functionalization, and the facile
      synthesis of natural and modified peptides. This review describes the assembly
      and properties of physical hydrogels that have been formed by the self
      association of very simple peptide building blocks. Natural short peptides, as
      short as dipeptides, can form ordered gel assemblies. Moreover, in the case of N
      terminal protection, even a protected amino acid can serve as an efficient
      hydrogelator. Further elucidation of hydrogelators' assembly, as well as the
      characterization of their physical properties, can guide the rational design of
      building blocks for a desired application. The possible mechanism of self
      assembly is discussed in line with the chemical nature of the short peptides.
      Different methods have been used to induce hydrogel assembly, which may
      significantly affect the mechanical characteristics of the resulting gels. Here,
      special emphasis is given to methods that allow either spatial control of
      hydrogel formation or modulation of physical properties of the gel. Finally, the
      parameters that influence hydrogelation are described, and insights for their
      design are provided. 

PMID- 23958779
TI  - Covalent immobilization of stem cell factor and stromal derived factor 1alpha for
      in vitro culture of hematopoietic progenitor cells.
AB  - Hematopoietic stem cells (HSCs) are currently utilized in the treatment of blood
      diseases, but widespread application of HSC therapeutics has been hindered by the
      limited availability of HSCs. With a better understanding of the HSC
      microenvironment and the ability to precisely recapitulate its components, we may
      be able to gain control of HSC behavior. In this work we developed a novel,
      biomimetic PEG hydrogel material as a substrate for this purpose and tested its
      potential with an anchorage-independent hematopoietic cell line, 32D clone 3
      cells. We immobilized a fibronectin-derived adhesive peptide sequence, RGDS; a
      cytokine critical in HSC self-renewal, stem cell factor (SCF); and a chemokine
      important in HSC homing and lodging, stromal derived factor 1alpha (SDF1alpha),
      onto the surfaces of poly(ethylene glycol) (PEG) hydrogels. To evaluate the
      system's capabilities, we observed the effects of the biomolecules on 32D cell
      adhesion and morphology. We demonstrated that the incorporation of RGDS onto the
      surfaces promotes 32D cell adhesion in a dose-dependent fashion. We also observed
      an additive response in adhesion on surfaces with RGDS in combination with either
      SCF or SDF1alpha. In addition, the average cell area increased and circularity
      decreased on gel surfaces containing immobilized SCF or SDF1alpha, indicating
      enhanced cell spreading. By recapitulating aspects of the HSC microenvironment
      using a PEG hydrogel scaffold, we have shown the ability to control the adhesion
      and spreading of the 32D cells and demonstrated the potential of the system for
      the culture of primary hematopoietic cell populations.

PMID- 23958782
TI  - Graphene and graphene oxide as new nanocarriers for drug delivery applications.
AB  - The biomedical applications of graphene-based materials, including drug delivery,
      have grown rapidly in the past few years. Graphene and graphene oxide have been
      extensively explored as some of the most promising biomaterials for biomedical
      applications due to their unique properties: two-dimensional planar structure,
      large surface area, chemical and mechanical stability, superb conductivity and
      good biocompatibility. These properties result in promising applications for the
      design of advanced drug delivery systems and delivery of a broad range of
      therapeutics. In this review we present an overview of recent advances in this
      field of research. We briefly describe current methods for the surface
      modification of graphene-based nanocarriers, their biocompatibility and toxicity,
      followed by a summary of the most appealing examples demonstrated for the
      delivery of anti-cancer drugs and genes. Additionally, new drug delivery concepts
      based on controlling mechanisms, including targeting and stimulation with pH,
      chemical interactions, thermal, photo- and magnetic induction, are discussed.
      Finally the review is summarized, with a brief conclusion of future prospects and
      challenges in this field.

PMID- 23958783
TI  - The delayed addition of human mesenchymal stem cells to pre-formed endothelial
      cell networks results in functional vascularization of a collagen
      glycosaminoglycan scaffold in vivo.
AB  - This paper demonstrates a method to engineer, in vitro, a nascent
      microvasculature within a collagen-glycosaminoglycan scaffold with a view to
      overcoming the major issue of graft failure due to avascular necrosis of tissue
      engineered constructs. Human umbilical vein endothelial cells (ECs) were cultured
      alone and in various co-culture combinations with human mesenchymal stem cells
      (MSCs) to determine their vasculogenic abilities in vitro. Results demonstrated
      that the delayed addition of MSCs to pre-formed EC networks, whereby MSCs act as
      pericytes to the nascent vessels, resulted in the best developed vasculature. The
      results also demonstrate that the crosstalk between ECs and MSCs during
      microvessel formation occurs in a highly regulated, spatio-temporal fashion,
      whereby the initial seeding of ECs results in platelet derived growth factor
      (PDGF) release; the subsequent addition of MSCs 3 days later leads to a cessation
      in PDGF production, coinciding with increased vascular endothelial cell growth
      factor expression and enhanced vessel formation. Functional assessment of these
      pre-engineered constructs in a subcutaneous rat implant model demonstrated
      anastomosis between the in vitro engineered vessels and the host vasculature,
      with significantly increased vascularization occurring in the co-culture group.
      This study has thus provided new information on the process of in vitro
      vasculogenesis within a three-dimensional porous scaffold for tissue engineering
      and demonstrates the potential for using these vascularized scaffolds in the
      repair of critical sized bone defects.

PMID- 23958784
TI  - Doxorubicin-loaded amphiphilic polypeptide-based nanoparticles as an efficient
      drug delivery system for cancer therapy.
AB  - An amphiphilic anionic copolymer, methoxy poly(ethylene glycol)-b-poly(l-glutamic
      acid-co-l-phenylalanine) (mPEG-b-P(Glu-co-Phe)), with three functionalized
      domains, was synthesized and used as a nanovehicle for cationic anticancer drug
      doxorubicin hydrochloride (DOX.HCl) delivery via electrostatic interactions for
      cancer treatment. The three domains displayed distinct functions: PEG block chain
      for prolonged circulation; poly(phenylalanine) domain for stabilizing the
      nanoparticle construct through hydrophobic/aromatic interactions; and the
      poly(glutamic acid) domain for providing electrostatic interactions with the
      cationic drug to be loaded. The copolymer could self-assemble into micellar-type
      nanoparticles, and DOX was successfully loaded into the interior of nanoparticles
      by simple mixing of DOX.HCl and the copolymer in the aqueous phase. DOX-loaded
      mPEG-b-P(Glu-co-Phe) nanoparticles (DOX-NP) had a superior drug-loading content
      (DLC) (21.7%), a high loading efficiency (almost 98%) and a pH-triggered release
      of DOX. The size of DOX-NP was ~140 nm, as determined by dynamic light scattering
      measurements and transmission electron microscopy. In vitro assays showed that
      DOX-NP exhibited higher cell proliferation inhibition and higher cell uptake in
      A549 cell lines compared with free DOX.HCl. Maximum tolerated dose (MTD) studies
      showed that DOX-NP demonstrated an excellent safety profile with a significantly
      higher MTD (15 mg DOX kg(-1)) than that of free DOX.HCl (5 mg DOX kg(-1)). The in
      vivo studies on the subcutaneous non-small cell lung cancer (A549) xenograft nude
      mice model confirmed that DOX-NP showed significant antitumor activity and
      reduced side effects, and then enhanced tumor accumulation as a result of the
      prolonged circulation in blood and the enhanced permeation and retention effect,
      compared with free DOX, indicating its great potential for cancer therapy.

PMID- 23958785
TI  - Molecular cloning, immunohistochemical localization, characterization and
      expression analysis of caspase-9 from the purse red common carp (Cyprinus carpio)
      exposed to cadmium.
AB  - Caspase-9, the essential initiator caspase is believed to play a central role in
      mitochondria-mediated apoptosis signaling. In this study, we isolated the caspase
      9 gene from common carp, one of the most important industrial aquatic animals in
      China using rapid amplification of cDNA ends (RACE). The deduced amino acid
      sequence of caspase-9, composed of 436 amino acids, showed approximately 47.6%
      identity and 64.7% similarity to human caspase-9. It also possessed a conserved
      caspase-associated recruitment domain (CARD), a large subunit and a small
      subunit. Phylogenetic analysis clearly demonstrated that caspase-9 formed a clade
      with cyprinid fish caspase-9. Real-time quantitative PCR analysis revealed that
      caspase-9 transcripts were not significantly increased in kidney after exposure
      to cadmium (Cd). Whereas caspase-9 cleaved fragments were detected using Western
      blot analysis with the same Cd treatment condition. Furthermore, the result of
      immunohistochemical detection showed immunoreactivities were predominantly
      limited to the cytoplasm of renal tubular epithelial cells and no remarkable
      changes of immunopositive staining were observed after Cd treatment. Accordingly,
      the results signify that caspase-9 may play an essential role in Cd induced
      apoptosis. 

PMID- 23958786
TI  - The brominated flame retardant TBECH activates the zebrafish (Danio rerio)
      androgen receptor, alters gene transcription and causes developmental
      disturbances.
AB  - Tetrabromoethylcyclohexane (TBECH) is a brominated flame retardant that has been
      shown to be a potent agonist to the human androgen receptor (AR). However, while
      it is present in the environment, it is not known if it interacts with AR from
      aquatic species. The present study was therefore aimed at improving our
      understanding of how TBECH affects aquatic animals using zebrafish as a model
      organism. In silico modeling demonstrated that TBECH diastereomers bind to the
      zebrafish androgen receptor (zAR) and in vitro and in vivo data showed that TBECH
      has androgenic properties. Deleterious effects of TBECH were studied on embryonic
      and juvenile zebrafish and qRT-PCR analysis in vitro and in vivo was performed to
      determine TBECH effects on gene regulation. TBECH was found to delay hatching at
      1 MUM and 10 MUM doses while morphological abnormalities and juvenile mortality
      was observed at 10 MUM. The qRT-PCR analysis showed alterations of multiple genes
      involved in chondrogenesis (cartilage development), metabolism and stress
      response. Thus, TBECH induces androgenic activity and has negative effects on
      zebrafish physiology and therefore its impact on the environment should be
      carefully monitored.

PMID- 23958787
TI  - Trivalent galactosyl-functionalized mesoporous silica nanoparticles as a target
      specific delivery system for boron neutron capture therapy.
AB  - A multi-functional mesoporous silica nanoparticle (MSN)-based boron neutron
      capture therapy (BNCT) agent, designated as T-Gal-B-Cy3@MSN, was synthesized with
      hydrophobic mesopores for incorporating a large amount of o-carborane (almost 60%
      (w/w) boron atoms per MSN), and the amines on the external surface were
      conjugated with trivalent galactosyl ligands and fluorescent dyes for cell
      targeting and imaging, respectively. The polar and hydrophilic galactosyl ligands
      enhance the water dispersibility of the BNCT agent and inhibit the possible
      leakage of o-carborane loaded in the MSN. Confocal microscopic images showed that
      T-Gal-B-Cy3@MSNs were endocytosed by cells and were then released from lysosomes
      into the cytoplasm of cells. Moreover, in comparison with the commonly used
      clinical BNCT agent, sodium borocaptate (BSH), T-Gal-B-Cy3@MSN provides a higher
      delivery efficiency (over 40-50 fold) of boron atoms and a better effect of BNCT
      in neutron irradiation experiments. MTT assays show a very low cytotoxicity for T
      Gal-B-Cy3@MSN over a 2 h incubation time. The results are promising for the
      design of multifunctional MSNs as potential BNCT agents for clinical use.

PMID- 23958788
TI  - Chilling and heat requirements for flowering in temperate  fruit trees.
AB  - Climate change has affected the rates of chilling and heat accumulation, which
      are vital for flowering and production, in temperate fruit trees, but few studies
      have been conducted in the cold-winter climates of East Asia. To evaluate tree
      responses to variation in chill and heat accumulation rates, partial least
      squares regression was used to correlate first flowering dates of chestnut
      (Castanea mollissima Blume) and jujube (Zizyphus jujube Mill.) in Beijing, China,
      with daily chill and heat accumulation between 1963 and 2008. The Dynamic Model
      and the Growing Degree Hour Model were used to convert daily records of minimum
      and maximum temperature into horticulturally meaningful metrics. Regression
      analyses identified the chilling and forcing periods for chestnut and jujube. The
      forcing periods started when half the chilling requirements were fulfilled. Over
      the past 50 years, heat accumulation during tree dormancy increased
      significantly, while chill accumulation remained relatively stable for both
      species. Heat accumulation was the main driver of bloom timing, with effects of
      variation in chill accumulation negligible in Beijing's cold-winter climate. It
      does not seem likely that reductions in chill will have a major effect on the
      studied species in Beijing in the near future. Such problems are much more likely
      for trees grown in locations that are substantially warmer than their native
      habitats, such as temperate species in the subtropics and tropics.

PMID- 23958789
TI  - Berry composition and climate: responses  and empirical models.
AB  - Climate is a strong modulator of berry composition. Accordingly, the projected
      change in climate is expected to impact on the composition of berries and of the
      resultant wines. However, the direction and extent of climate change impact on
      fruit composition of winegrape cultivars are not fully known. This study utilised
      a climate gradient along a 700 km transect, covering all wine regions of Western
      Australia, to explore and empirically describe influences of climate on
      anthocyanins, pH and titratable acidity (TA) levels in two or three cultivars of
      Vitis vinifera (Cabernet Sauvignon, Chardonnay and Shiraz). The results showed
      that, at a common maturity of 22 degrees  Brix total soluble solids, berries from
      the warmer regions had low levels of anthocyanins and TA as well as high pH
      compared to berries from the cooler regions. Most of these regional variations in
      berry composition reflected the prevailing climatic conditions of the regions.
      Thus, depending on cultivar, 82-87 % of TA, 83 % of anthocyanins and about half
      of the pH variations across the gradient were explained by climate-variable-based
      empirical models. Some of the variables that were relevant in describing the
      variations in berry attributes included: diurnal ranges and ripening period
      temperature (TA), vapour pressure deficit in October and growing degree days
      (pH), and ripening period temperatures (anthocyanins). Further, the rates of
      change in these berry attributes in response to climate variables were cultivar
      dependent. Based on the observed patterns along the climate gradient, it is
      concluded that: (1) in a warming climate, all other things being equal, berry
      anthocyanins and TA levels will decline whereas pH levels will rise; and (2)
      despite variations in non-climatic factors (e.g. soil type and management) along
      the sampling transect, variations in TA and anthocyanins were satisfactorily
      described using climate-variable-based empirical models, indicating the
      overriding impact of climate on berry composition. The models presented here are
      useful tools for assessing likely changes in berry TA and anthocyanins in
      response to changing climate for the wine regions and cultivars covered in this
      study.

PMID- 23958790
TI  - Artesunate inhibits the growth of gastric cancer cells through the mechanism of
      promoting oncosis both in vitro and in vivo.
AB  - This study aims to investigate the significance and mechanism of artesunate
      involved in suppressing the proliferation of gastric cancer in vitro and in vivo.
      In the in-vitro experiments, artesunate inhibited the growth of gastric cancer
      cell lines (SGC-7901, BGC-823, and AGS) with concentration-dependent activity,
      with no significant effect on GES-1 cells. BGC-823 cells treated with artesunate
      showed the typical morphologic features of oncosis rather than apoptosis.
      Meanwhile, we observed calcium overload, downregulation of vascular endothelial
      growth factor expression, and upregulation of calpain-2 expression in the
      artesunate-treated BGC-823 cells. In addition, the in-vivo study showed that
      artesunate produced a dose-dependent tumor regression in nude mice. The antitumor
      activity of 240 mg/kg artesunate was similar to that of 10 mg/kg docetaxel.
      Furthermore, compared with the control group, no significant difference was
      observed in the body weight of artesunate-treated nude mice other than docetaxel
      treated nude mice. These observations show that artesunate has concentration
      dependent inhibitory activities against gastric cancer in vitro and in vivo by
      promoting cell oncosis through an impact of calcium, vascular endothelial growth
      factor, and calpain-2 expression.

PMID- 23958791
TI  - Herbal compound triptolide synergistically enhanced antitumor activity of
      vasostatin120-180.
AB  - Angiogenesis is essential for the survival and growth of most tumors. As such,
      targeting the tumor neovasculature is an attractive strategy for effective cancer
      therapy. Angiogenesis inhibitors have strong therapeutic potential as antitumor
      agents in suppressing tumor growth and metastatic progression. The functional
      domain within amino acid residues 120-180 of vasostatin (VAS) has been confirmed
      to be effective in inhibiting the proliferation, migration, and invasiveness of
      cancer cells by its suppressive capacity against angiogenesis. Triptolide (TPL)
      is an active component extracted from the traditional Chinese herbal medicine
      Tripterygium wilfordii Hook F that has shown antitumor activities in various
      cancer cell types. However, its therapeutic application is limited by its
      toxicity in normal tissues and complications caused in patients. In this study,
      we attempted to investigate the synergistic antitumor activity of TPL and VAS in
      solid tumor cells. Our results showed that the sensitivity of combined therapy
      using TPL and VAS was higher than that of monotherapy using TPL or VAS. Apoptosis
      induced by the combined treatment was accompanied by activation of caspase-9,
      caspase-8, and caspase-3. Upregulation of proapoptotic protein (Bax, Bak, and
      Bad) expression and suppression of NF-kappaB transcriptional activity and its
      targeting antiapoptotic genes (c-FLIP, cIAP, Bcl-2, Bcl-xl, and Mcl-1) may
      contribute to the synergistic effects of this combination therapy. Further, using
      a mouse xenograft model, we demonstrated that combined treatment completely
      suppressed tumor growth as compared with treatment with TPL or VAS alone. These
      results suggest that the combination of TPL and VAS at lower concentrations may
      produce a synergistic antitumor effect that warrants further investigation for
      its potential clinical applications.

PMID- 23958792
TI  - Identification of novel nucleus pulposus markers: Interspecies variations and
      implications for cell-based therapiesfor intervertebral disc degeneration.
AB  - Mesenchymal stem-cell based therapies have been proposed as novel treatments for
      intervertebral disc degeneration, a prevalent and disabling condition associated
      with back pain. The development of these treatment strategies, however, has been
      hindered by the incomplete understanding of the human nucleus pulposus phenotype
      and by an inaccurate interpretation and translation of animal to human research.
      This review summarises recent work characterising the nucleus pulposus phenotype
      in different animal models and in humans and integrates their findings with the
      anatomical and physiological differences between these species. Understanding
      this phenotype is paramount to guarantee that implanted cells restore the native
      functions of the intervertebral disc. Cite this article: Bone Joint Res
      2013;2:169-78. 

PMID- 23958793
TI  - The effects of 30 days resveratrol supplementation on adipose tissue morphology
      and gene expression patterns in obese men.
AB  - Polyphenolic compounds, such as resveratrol, have recently received widespread
      interest because of their ability to mimic effects of calorie restriction. The
      objective of the present study was to gain more insight into the effects of 30
      days resveratrol supplementation on adipose tissue morphology and underlying
      processes. Eleven healthy obese men were supplemented with placebo and
      resveratrol for 30 days (150 mg per day), separated by a 4-week washout period in
      a double-blind randomized crossover design. A postprandial abdominal subcutaneous
      adipose tissue biopsy was collected to assess adipose tissue morphology and gene
      expression using microarray analysis. Resveratrol significantly decreased
      adipocyte size, with a shift toward a reduction in the proportion of large and
      very-large adipocytes and an increase in small adipocytes. Microarray analysis
      revealed downregulation of Wnt and Notch signaling pathways and upregulation of
      pathways involved in cell cycle regulation after resveratrol supplementation,
      suggesting enhanced adipogenesis. Furthermore, lysosomal/phagosomal pathway and
      transcription factor EB were upregulated reflecting an alternative pathway of
      lipid breakdown by autophagy. Further research is necessary to investigate
      whether resveratrol improves adipose tissue function. 

PMID- 23958794
TI  - Excessive gestational weight gain over multiple pregnancies and the prevalence of
      obesity at age 40.
AB  - OBJECTIVE: Although several studies have found an association between excessive
      gestational weight gain (GWG) and obesity later in life, to the best of our
      knowledge, no studies have explored the role of GWG events across the life
      course. DESIGN AND METHODS: We describe how the prevalence of midlife obesity
      (BMI?30 at age 40 or 41) among women varies by life course patterns of GWG (using
      2009 IOM guidelines) in the USA's National Longitudinal Survey of Youth 1979
      cohort. RESULTS: Among women who reported 1-3 births before age 40, the
      prevalence of midlife obesity increased with a rising number of excessive GWG
      events: from none (23.4%, n=875) to one (37.6%, n=707), from none (23.4%, n=875)
      to two (46.8%, n=427) and from none (23.4%, n=875) to three (54.6%, n=108),
      P<0.00005 for trend. Obesity prevalence was similar for the same number of
      excessive GWG events, regardless of parity. No clear pattern emerged for the
      sequencing of excessive GWG event(s) and later obesity. CONCLUSIONS: In our
      descriptive exploratory study, excessive GWG events appear to be associated with
      increased prevalence of obesity for parous women, suggesting the importance of
      preventive interventions regardless of timing of pregnancy-related weight changes
      over the life course.

PMID- 23958795
TI  - Alcohol increases hypnotic susceptibility.
AB  - One approach to hypnosis suggests that for hypnotic experience to occur frontal
      lobe activity must be attenuated. For example, cold control theory posits that a
      lack of awareness of intentions is responsible for the experience of
      involuntariness and/or the subjective reality of hypnotic suggestions. The mid
      dorso-lateral prefrontal cortex and the ACC are candidate regions for such
      awareness. Alcohol impairs frontal lobe executive function. This study examined
      whether alcohol affects hypnotisability. We administered 0.8 mg/kg of alcohol or
      a placebo to 32 medium susceptible participants. They were subsequently
      hypnotised and given hypnotic suggestions. All participants believed they had
      received some alcohol. Participants in the alcohol condition were more
      susceptible to hypnotic suggestions than participants in the placebo condition.
      Impaired frontal lobe activity facilitates hypnotic responding, which supports
      theories postulating that attenuation of executive function facilitates hypnotic
      response, and contradicts theories postulating that hypnotic response involves
      enhanced inhibitory, attentional or other executive function.

PMID- 23958798
TI  - Rheumatoid arthritis: role for infliximab uncertain as targeted DMARD
      combinations achieve effective disease control.

PMID- 23958796
TI  - Insights from human genetic studies into the pathways involved in osteoarthritis.
AB  - Genetic studies have revealed that most loci associated with osteoarthritis (OA)
      show ethnic stratification, with limited overlap between Asian and European
      populations. Consequently, such studies have often focused on particular ethnic
      groups, with those performed in European cohorts yielding the most replicated
      associations. As for other common diseases, the OA susceptibility loci mapped to
      date account for only a fraction of disease heritability. Nevertheless, analysis
      of these loci could identify biological pathways related to OA pathogenesis. Such
      an approach is taken in this Review and provides valuable insights into OA
      aetiology. For example, several of the loci associated with OA contain genes
      encoding key regulators of skeletogenesis and endochondral ossification.
      Furthermore, direct and indirect regulation of gene transcription is highlighted
      as an important factor in this disease. Interestingly, genes encoding structural
      proteins of the cartilage extracellular matrix do not seem to be a repository for
      OA susceptibility. Therefore, susceptibility might operate at a regulatory rather
      than a structural level, which is a potentially promising finding, as the
      activities of regulators are amenable to therapeutic modulation. Greater clarity
      will emerge as more association signals are identified; nonetheless, patterns of
      aetiology are clearly discernible, from a molecular perspective, even with the
      relatively small number currently available. 

PMID- 23958797
TI  - Annexin A1: potential for glucocorticoid sparing in RA.
AB  - Glucocorticoids have broad-ranging and powerful anti-inflammatory and
      immunomodulatory effects. Unsurprisingly, therefore, glucocorticoids are widely
      and persistently used to treat a large number of inflammatory diseases, including
      rheumatoid arthritis (RA), despite the well-described adverse effects of these
      drugs. Annexin A1 is a glucocorticoid-induced molecule that is known to replicate
      many of the described anti-inflammatory effects of glucocorticoids. In addition
      to the well-documented roles of this protein in neutrophil function, emerging
      evidence suggests that annexin A1 is involved in the modulation of T-cell
      function and the adaptive immune responses relevant to RA. Interest in annexin A1
      was renewed after the delineation of the receptors for this protein. This
      breakthrough also led to advances in our understanding of anti-inflammatory
      annexin A1 mimetic peptides and agonistic compounds targeting these receptors,
      particularly those specific for the receptor N-formyl peptide receptor 2 (FPR2).
      Herein, we review the current knowledge of the biological activities of annexin
      A1 and their relevance to RA pathogenesis. We also discuss the potential of
      annexin A1 mimics and strategies aimed at potentiating annexin A1 signalling to
      become viable approaches to minimizing glucocorticoid use in RA and other
      inflammatory disorders.

PMID- 23958799
TI  - Regional and segmental differences in the embryonic expression of a putative
      leech Hox gene, Lox2, by central neurons immunoreactive to FMRFamide-like
      neuropeptides.
AB  - We performed immunofluorescence experiments using a rat polyclonal antibody on
      formaldehyde-fixed whole-mount embryos to characterize the expression of a
      putative leech Hox gene, Lox2, during embryonic development. The main goal was to
      determine whether the differentiation of subsets of FMRFamide-like immunoreactive
      (FLI) neurons coincide with the expression domain of Lox2. The earliest
      expression of Lox2 was detected in relatively large, prominent nuclei in the
      posterior region at embryonic day 4, a very early stage. Lox2 expression was also
      detected in subsets of central neurons (neurons located in the CNS) located in
      midbody ganglia 6 (M6)-M21. In addition, Lox2 was expressed by a number of
      segment-specific and segmentally repeated central FLI neurons. Lox2-positive FLI
      neurons of interest included some of those previously identified: the rostral
      most ventral (RMV) neurons, the circular ventral (CV) neurons, and cell 261. The
      paired RMVs, which are located in all midbody ganglia, expressed Lox2 only in M7
      M19. The CV neurons, specialized motor neurons that innervate the circular
      ventral muscles of the body wall, expressed Lox2 in M7-M19. The putative cell 261
      expressed Lox2 in M7-M12, where Lox1 is also expressed. FMRFamide staining in
      putative segmental homologs of cell 261 was not detected in other segmental
      ganglia. Our results suggest a role for Lox2 in very early embryonic development
      (before the formation of the CNS), and in the differentiation of segmentally
      repeated and region-specific FLI neurons. 

PMID- 23958800
TI  - Depolymerization of crystalline cellulose catalyzed by acidic ionic liquids
      grafted onto sponge-like nanoporous polymers.
AB  - The acidic ionic liquid (IL) functionalized polymer (PDVB-SO3H-[C3vim][SO3CF3])
      possesses abundant nanoporous structures, strong acid strength and unique
      capability for deconstruction of crystalline cellulose into sugars in ILs. The
      polymer shows much improved catalytic activities in comparison with mineral
      acids, homogeneous acidic ionic liquids and the acidic resins such as Amberlyst
      15. The enhanced catalytic activity found in the polymer is attributed to
      synergistic effects between the strongly acidic group and the ILs grafted onto
      the polymer, which by itself is capable of breaking down the crystalline
      structures of cellulose. This study may help develop cost-effective and green
      routes for conversion of biomass to fuels. 

PMID- 23958801
TI  - Development and application of effective pairwise potentials for UO2(n+),
      NpO2(n+), PuO2(n+), and AmO2(n+) (n = 1, 2) ions with water.
AB  - Intra- and intermolecular force field parameters for the interaction of actinyl
      ions (AnO2(n+), where, An = U, Np, Pu, Am and n = 1, 2) with water have been
      developed using quantum mechanical calculations. Water was modeled with the
      extended simple point charge potential (SPC/E). The resulting force field
      consists of a simple form in which intermolecular interactions are modeled with
      pairwise Lennard-Jones functions plus partial charge terms. Intramolecular bond
      stretching and angle bending are treated with harmonic functions. The new
      potentials were used to carry out extensive molecular dynamics simulations for
      each hydrated ion. Computed bond lengths, bond angles and coordination numbers
      agree well with known values and previous simulations. Hydration free energies,
      computed from molecular dynamics simulations as well as from quantum simulations
      with a solvation model, were in reasonable agreement with estimated experimental
      values. 

PMID- 23958802
TI  - Formation of an unprecedented (CuBr)5 cluster and a zeolite-type 2D-coordination
      polymer: a surprising halide effect.
AB  - A unique pentanuclear cluster within a zeolite-type polymer ([Cu5(MU4-Br)(MU3
      Br)2(MU2-Br)2](MU2-MeSPr)3)n (1; void space >81%) and a luminescent 1D ([Cu(MU3
      I)]4(MeSPr)3)n polymer, 2, are formed when MeSPr reacts with CuBr and CuI.

PMID- 23958803
TI  - Public preferences about secondary uses of electronic health information.
AB  - IMPORTANCE: As health information technology grows, secondary uses of personal
      health information offer promise in advancing research, public health, and health
      care. Public perceptions about sharing personal health data are important for
      establishing and evaluating ethical and regulatory structures to oversee the use
      of these data. OBJECTIVE: To measure patient preferences about sharing their
      electronic health information for secondary purposes (other than their own health
      care). DESIGN, SETTING, AND PARTICIPANTS: In this conjoint analysis study, we
      surveyed 3336 adults (568 Hispanic, 500 non-Hispanic African American, and 2268
      non-Hispanic white); participants were randomized to 6 of 18 scenarios describing
      secondary uses of electronic health information, constructed with 3 attributes:
      uses (research, quality improvement, or commercial marketing), users (university
      hospitals, commercial enterprises, or public health departments), and data
      sensitivity (whether it included genetic information about their own cancer
      risk). This design enabled participants to reveal their preferences for secondary
      uses of their personal health information. MAIN OUTCOMES AND MEASURES:
      Participants responded to each conjoint scenario by rating their willingness to
      share their electronic personal health information on a 1 to 10 scale (1
      represents low willingness; 10, high willingness). Conjoint analysis yields
      importance weights reflecting the contribution of a dimension (use, user, or
      sensitivity) to willingness to share personal health information. RESULTS: The
      use of data was a more important factor in the conjoint analysis (importance
      weight, 64.3%) than the user (importance weight, 32.6%) and data sensitivity
      (importance weight, 3.1%). In unadjusted linear regression models, marketing uses
      (beta = -1.55), quality improvement uses (beta = -0.51), drug company users (beta
      = -0.80), and public health department users (beta = -0.52) were associated with
      less willingness to share health information than research uses and university
      hospital users (all P < .001). Hispanics and African Americans differentiated
      less than whites between uses. CONCLUSIONS AND RELEVANCE: Participants cared most
      about the specific purpose for using their health information, although
      differences were smaller among racial and ethnic minorities. The user of the
      information was of secondary importance, and the sensitivity was not a
      significant factor. These preferences should be considered in policies governing
      secondary uses of health information.

PMID- 23958804
TI  - Assessment of diet and physical activity of brazilian schoolchildren: usability
      testing of a web-based questionnaire.
AB  - BACKGROUND: Information and communication technology (ICT) has been used with
      increasing frequency for the assessment of diet and physical activity in health
      surveys. A number of Web-based questionnaires have been developed for children
      and adolescents. However, their usability characteristics have scarcely been
      reported, despite their potential importance for improving the feasibility and
      validity of ICT-based methods. OBJECTIVE: The objective of this study was to
      describe the usability evaluation of the Consumo Alimentar e Atividade Fisica de
      Escolares (CAAFE) questionnaire (Food Consumption and Physical Activity
      Questionnaire for schoolchildren), a new Web-based survey tool for the self
      assessment of diet and physical activity by schoolchildren. METHODS: A total of
      114 schoolchildren aged 6 to 12 years took part in questionnaire usability
      testing carried out in computer classrooms at five elementary schools in the city
      of Florianopolis, Brazil. Schoolchildren used a personal computer (PC) equipped
      with software for recording what is on the computer screen and the children's
      speech during usability testing. Quantitative and qualitative analyses took into
      account objective usability metrics such as error counts and time to complete a
      task. Data on the main difficulties in accomplishing the task and the level of
      satisfaction expressed by the children were assessed by the observers using a
      standardized form and interviews with the children. Descriptive statistics and
      content analysis were used to summarize both the quantitative and the qualitative
      aspects of the data obtained. RESULTS: The mean time for completing the
      questionnaire was 13.7 minutes (SD 3.68). Compared to the children in 2nd or 3rd
      grades, those in 4th or 5th grades spent less time completing the questionnaire
      (median 12.4 vs 13.3 minutes, P=.022), asked for help less frequently (median 0
      vs 1.0 count, P=.005), had a lower error count (median 2.0 vs 8.0 count, P<.001),
      and obtained a higher overall performance score (median 73.0 vs 68.0, P=.005).
      Children with a PC at home spent less time completing the questionnaire (median
      12.3 vs 14.9 minutes, P<.001), had a lower overall error count (median 2.0 vs 9.0
      count, P=.03), and had a higher performance score (median 72.0 vs 64.0, P=.005)
      compared to the children without a PC at home. The most common difficulty in
      completing the questionnaire was in using the scroll bar. The majority of
      children reported a positive evaluation (liked a lot or liked) for the four
      design elements, which were evaluated. CONCLUSIONS: The results of the present
      study provided feedback to improve the final version of the CAAFE questionnaire.
      Quantitative data showed minor errors and system failures, while qualitative data
      indicated that, overall, the children enjoyed the CAAFE questionnaire. Grade
      levels and PC use must be taken into account in Web-based tools designed for
      children.

PMID- 23958805
TI  - "He who knows syphilis knows medicine": the return of an old devil.

PMID- 23958806
TI  - Ketamine increases striatal dopamine release and hyperlocomotion in adult rats
      after postnatal functional blockade of the prefrontal cortex.
AB  - Schizophrenia is a complex psychiatric disorder that may result from defective
      connectivity, of neurodevelopmental origin, between several integrative brain
      regions. Different anomalies consistent with brain development failures have been
      observed in patients' left prefrontal cortex (PFC). A striatal dopaminergic
      functional disturbance is also commonly acknowledged in schizophrenia and could
      be related to a dysfunctioning of dopamine-glutamate interactions. Non
      competitive NMDA antagonists, such as ketamine, can induce psychotic symptoms in
      healthy individuals and worsen these symptoms in patients with schizophrenia. Our
      study set out to investigate the consequences of neonatal functional blockade of
      the PFC for dopaminergic and behavioral reactivity to ketamine in adult rats.
      Following tetrodotoxin (TTX) inactivation of the left PFC at postnatal day 8,
      dopaminergic responses induced by ketamine (5 mg/kg, 10 mg/kg, 20 mg/kg sc) were
      monitored using in vivo voltammetry in the left part of the dorsal striatum in
      freely moving adult rats. Dopaminergic responses and locomotor activity were
      followed in parallel. Compared to PBS animals, in rats microinjected with TTX,
      ketamine challenge induced a greater release of dopamine in the dorsal striatum
      for the highest dose (20 mg/kg sc) and the intermediate dose (10mg/kg sc). A
      higher increase in locomotor activity in TTX animals was observed only for the
      highest dose of ketamine (20 mg/kg sc). These data suggest transient inactivation
      of the PFC during early development results in greater behavioral and striatal
      dopaminergic reactivity to ketamine in adulthood. Our study provides an anatomo
      functional framework that may contribute toward a better understanding of the
      involvement of NMDA glutamatergic receptors in schizophrenia.

PMID- 23958807
TI  - Nanostructured N-doped TiO2 marigold flowers for an efficient solar hydrogen
      production from H2S.
AB  - Nitrogen-doped TiO2 nanostructures in the form of marigold flowers have been
      synthesized for the first time using a facile solvothermal method. The structural
      analysis has shown that such an N-doped TiO2 system crystallizes in the anatase
      structure. The optical absorption spectra have clearly shown the shift in the
      absorption edge towards the visible-light range, which indicates successful
      nitrogen doping. The nitrogen doping has been further confirmed by
      photoluminescence and photoemission spectroscopy. Microscopy studies have shown
      the thin nanosheets (petals) of N-TiO2 with a thickness of ~2-3 nm, assembled in
      the form of the marigold flower with a high surface area (224 m(2) g(-1)). The N
      TiO2 nanostructure with marigold flowers is an efficient photocatalyst for the
      decomposition of H2S and production of hydrogen under solar light. The maximum
      hydrogen evolution obtained is higher than other known N-TiO2 systems. It is
      noteworthy that photohydrogen production using the unique marigold flowers of N
      TiO2 from abundant H2S under solar light is hitherto unattempted. The proposed
      synthesis method can also be utilized to design other hierarchical nanostructured
      N-doped metal oxides.

PMID- 23958808
TI  - Bactericidal antibody persistence 2 years after immunization with 2
      investigational serogroup B meningococcal vaccines at 6, 8 and 12 months and
      immunogenicity of preschool booster doses: a follow-on study to a randomized
      clinical trial.
AB  - BACKGROUND: In a previous study, 60 infants receiving an investigational
      serogroup B meningococcal vaccine containing recombinant meningococcal proteins
      alone (rMenB) or combined with an outer membrane vesicle from Neisseria
      meningitidis (4CMenB) at 6, 8 and 12 months of age produced serum bactericidal
      antibodies (SBAs) against meningococcal strains expressing vaccine antigens. We
      studied persistence of this response and the response to a booster dose of
      vaccine. METHODS: In this extension study, SBA titers were evaluated before and
      after a booster dose of rMenB or 4CMenB at 40 months of age. MenB vaccine naive
      age-matched children served as a control group. RESULTS: Before the booster
      doses, the proportions of 4CMenB recipients with SBA titers >=1:4 were 36% (n =
      14, 95% confidence interval: 13-65%) for strain 44/76-SL, 100% (77-100%) for
      5/99, 14% (2-43%) for NZ98/254 and 79% (49-95%) for M10713. These percentages
      were 14% to 29% for rMenB recipients (n = 14), except for 5/99 (93%, 66-100%).
      For controls (n = 40), these proportions were <=3% for all strains except M10713
      (53%, 36-68%). One month after the boosters, >=93% of 4CMenB recipients had SBA
      titers >=1:4 for all 4 strains. For controls receiving their first dose of
      4CMenB, 23% (11-39%) had SBA titers >=1:4 for NZ98/254, compared with 62% to 87%
      for the remaining strains. CONCLUSIONS: Bactericidal antibodies wane after infant
      immunization with rMenB or 4CMenB, but there is an anamnestic response to a
      booster dose. Booster doses of 4CMenB may be required to maintain immune
      protection through childhood and adolescence.

PMID- 23958809
TI  - Diverging trends in gastroenteritis hospitalizations during 2 decades in western
      Australian Aboriginal and non-Aboriginal children.
AB  - BACKGROUND: Gastroenteritis is a major cause of pediatric morbidity. We describe
      temporal, spatial and seasonal trends in age-specific gastroenteritis
      hospitalizations among Aboriginal and non-Aboriginal Australian children during 2
      decades, providing a baseline to evaluate the impact of a rotavirus vaccine
      program begun in 2007. METHODS: We conducted a population-based, data linkage
      study of Aboriginal and non-Aboriginal births in Western Australia, 1983 to 2006,
      and analyzed gastroenteritis-coded hospitalizations before age 15 years in the
      cohort of 596,465 births. Hospitalization rates in Aboriginal and non-Aboriginal
      children and between geographical regions were compared between 1983 to 1994 and
      1995 to 2006. RESULTS: Gastroenteritis rates were highest in children 6-11 months
      of age (Aboriginal: 259.3/1000/annum; non-Aboriginal: 22.7/1000/annum). Rates
      declined in Aboriginal children between 1983 to 1994 and 1995 to 2006,
      particularly in those 12-17 months of age (309/1000 to 179/1000). Rates in non
      Aboriginal children<5 years increased 10-40%. The disparity for gastroenteritis
      rates between Aboriginal and non-Aboriginal children<5 years declined from being
      15.4 times higher to 7.6 times higher in those aged 12-17 months and from 8.4 to
      4.4 in those aged 2-4 years. Rates were highest in rural and remote regions, and
      diverging temporal trends were seen in different geographical regions.
      Seasonality varied between Aboriginal and non-Aboriginal children and climatic
      zones. CONCLUSIONS: This is the largest study of gastroenteritis hospitalization
      trends in children. We found diverging trends of gastroenteritis hospitalization
      rates in Aboriginal and non-Aboriginal children. Although rates have declined in
      Aboriginal children, disparity between Aboriginal and non-Aboriginal children
      continues. Our findings highlight the need to consider age, ethnicity,
      seasonality and climate when evaluating rotavirus vaccine programs.

PMID- 23958811
TI  - Streptococcus pneumoniae as a uropathogen in children with urinary tract
      abnormalities.
AB  - We describe 3 children with urinary tract abnormalities and large numbers of
      Streptococcus pneumoniae in their urine, along with a brief review of previously
      reported cases. These findings strongly suggest that S. pneumoniae is a
      uropathogen, especially in children with urinary tract abnormalities. 

PMID- 23958810
TI  - Safety and pharmacokinetic profiles of repeated-dose micafungin in children and
      adolescents treated for invasive candidiasis.
AB  - BACKGROUND: Micafungin is an echinocandin with proven efficacy against a broad
      range of fungal infections, including those caused by Candida spp. OBJECTIVE: To
      evaluate the safety and pharmacokinetics of once-daily 3 mg/kg and 4.5 mg/kg
      micafungin in children with proven, probable or suspected invasive candidiasis.
      METHODS: Micafungin safety and pharmacokinetics were assessed in 2 phase I, open
      label, repeat-dose trials. In Study 2101, children aged 2-16 years were grouped
      by weight to receive 3 mg/kg (>=25 kg) or 4.5 mg/kg (<25 kg) intravenous
      micafungin for 10-14 days. In Study 2102, children aged 4 months to <2 years
      received 4.5 mg/kg micafungin. Study protocols were otherwise identical. RESULTS:
      Safety was analyzed in 78 and 9 children in Studies 2101 and 2102, respectively.
      Although adverse events (AEs) were experienced by most children (2101: n=62;
      2102: n=9), micafungin-related AEs were less common (2101: n=28; 2102: n=1), and
      the number of patients discontinuing due to AEs was low (2101: n=4; 2102: n=1).
      The most common micafungin-related AEs were infusion-associated symptoms, pyrexia
      and hypomagnesemia (Study 2101), and liver function abnormalities (Study 2102).
      The micafungin pharmacokinetic profile was similar to that seen in other studies
      conducted in children, but different than that observed in adults. CONCLUSIONS:
      In this small cohort of children, once-daily doses of 3 mg/kg and 4.5 mg/kg
      micafungin were well tolerated. Pharmacokinetic data will be combined in a
      population pharmacokinetic analysis to support US dosing recommendations in
      children.

PMID- 23958812
TI  - Neonatal and pediatric antimicrobial stewardship programs in Europe-defining the
      research agenda.
AB  - The relationship between suboptimal use of antimicrobials and antimicrobial
      resistance has become increasingly clear. Despite significant international
      effort aimed at reducing inappropriate antimicrobial prescribing in hospitals,
      antimicrobial resistance remains a major public health threat. Antimicrobial
      Stewardship Programs (ASPs) comprise a series of measures aimed at optimizing the
      use of antimicrobials, while improving the quality of patient care and promoting
      cost-effectiveness. This discussion article aims to summarize some of the
      approaches that have been used in neonatal and pediatric ASPs, with a particular
      focus on the European healthcare setting. Current evidence demonstrates neonatal
      and pediatric ASPs to be safe, practical to implement, generally cost-effective
      and possibly associated with a reduction in antimicrobial resistance rates. This
      review identified that, despite the recognized need for additional evidence and
      information on implementation, published data on pediatric ASPs derives mainly
      from the United States, with very few published reports on formal ASPs in
      European children's hospitals. Consequently, the optimal method of implementation
      remains unknown within a European setting. Future research needs to include novel
      study designs on how best to introduce ASPs, monitoring of clinically relevant
      outcomes and cost-effectiveness with improved measurement of the impact on
      antimicrobial resistance. 

PMID- 23958813
TI  - Consequences of prior use of full-dose ritonavir as single protease inhibitor as
      part of combination antiretroviral regimens on the future therapy choices in HIV
      1-infected children.
AB  - BACKGROUND: South African HIV-infected infants below age 6 months and children
      younger than 3 years on concomitant antimycobacterial treatment received full
      dose ritonavir single protease inhibitor (RTV-sPI), together with 2 nucleoside
      reverse transcriptase inhibitors, from 2004 until 2008. Use of RTV-sPI has been
      described as a risk factor for PI drug resistance, but the extent of this
      resistance is unknown. AIM: This research assesses clinical and virological
      outcome of a pediatric RTV-sPI cohort at a large South African antiretroviral
      therapy (ART) site in a high-burden tuberculosis setting, including resistance
      mutations in those failing ART. METHODS: All children initiated at Kalafong
      hospital before December 2008, who ever received RTV-sPI-based regimens, were
      assessed for patient outcome, virological failure and drug resistance. HIV viral
      loads were done 6-monthly and HIV genotyping since 2009. RESULTS: There were 178
      children who ever received RTV-sPI, with a mean age at ART initiation of 1.4
      years. Of the 135 children (76%) with >6 months follow-up, 17 children (13%)
      never had viral suppression, whereas another 25 (18%) developed virological
      failure later. Nineteen of 26 children (73%) with genotypic resistance results
      had major PI mutations. CONCLUSIONS: Treatment failure is not a universal feature
      in children with prior exposure to RTV-sPI regimens, but the significant
      proportion (31%) with virological failure is of concern due to high prevalence of
      major PI- and multiclass mutations. These children currently have no treatment
      options in the South African public sector, highlighting the urgent need for
      access to alternative ART regimens to ensure improved outcomes.

PMID- 23958814
TI  - A hospital-based surveillance of rotavirus gastroenteritis in children <5 years
      of age in Singapore.
AB  - BACKGROUND: In Singapore, 2 rotavirus vaccines were licensed in October 2005 and
      July 2007, respectively, for vaccinating infants aged >= 6 weeks against
      rotavirus gastroenteritis. These vaccines are optional and are not included in
      the National Childhood Immunization Program. This study aimed to determine the
      incidence of rotavirus gastroenteritis-associated hospitalizations among children
      <5 years of age. METHODS: Children <5 years, who were hospitalized for acute
      gastro enteritis, were enrolled between September 2005 and April 2008. Stool
      samples were tested for the presence and serotyping of rotavirus. Incidence and
      proportion of gastroenteritis and rotavirus gastroenteritis cases were calculated
      with 95% confidence intervals. RESULTS: Among 1976 children included in the
      according-to-protocol cohort, 781 were rotavirus positive with a median age of 24
      months (range: 0-59 months). The overall incidence of rotavirus gastroenteritis
      hospitalizations during the entire study period in children <5 years of age was
      4.6 (95% confidence interval: 4.3-4.9) per 1000 person-years with the highest
      number of cases observed in children 13-24 months of age (26.5%). G1P[8] (18.3%)
      and G9P[8] (9.9%) were the most common rotavirus types. Rotavirus gastroenteritis
      hospitalizations peaked between January and March. CONCLUSION: Rotavirus
      infection was the primary cause of acute gastro enteritis hospitalizations among
      children <5 years of age, constituting nearly one-third of gastroenteritis
      hospitalizations in Singapore. The predominant strain observed in Singapore was
      G1P[8]. Results of this study suggest the need for implementation of rotavirus
      vaccination into National Childhood Immunization Program in Singapore.

PMID- 23958815
TI  - Staphylococcal native valve endocarditis with iris abscess and intracranial
      hemorrhage in an adolescent girl.
AB  - Native valve infective endocarditis by Staphylococcus aureus is a well-known
      entity. Metastatic eye abscess and intracranial hemorrhage are rare
      manifestations of infective endocarditis. We describe an adolescent girl who
      presented with staphylococcal native valve endocarditis with metastatic iris
      abscesses and after valve replacement surgery, succumbed to her illness as a
      result of an intracranial hemorrhage. 

PMID- 23958816
TI  - Ambulatory gastric lavages provide better yields of Mycobacterium tuberculosis
      than induced sputum in children with intrathoracic tuberculosis.
AB  - OBJECTIVE: To compare mycobacterial yield by induced sputum (IS) and gastric
      lavage (GL), performed on an ambulatory basis in children with probable
      intrathoracic tuberculosis. DESIGN: Diagnostic accuracy study. SETTING: Two
      tertiary care hospitals in Delhi, India. PATIENTS: Children aged 6 months to 15
      years with newly diagnosed intrathoracic tuberculosis. METHODS: GL and IS were
      performed in children on 2 consecutive days on ambulatory basis. Samples were
      examined by Ziehl-Neelsen staining and cultured on an automated BACTEC-MGIT 960
      system. OUTCOME MEASURE: Mycobacterial yields (smear and culture) for the 2
      sample types (IS and GL) were compared. RESULTS: Four hundred three children
      (56.6% girls), median age 111 months (interquartile range: 68, 144) were
      enrolled. Overall yield for acid-fast bacilli and/or Mycobacterium tuberculosis
      (MTB) by either IS and/or GL was 152 (37.7%). Acid-fast bacilli positivity from
      IS and GL were 5.7% (23) and 10.4% (42), respectively. Confirmed MTB on culture
      from IS and GL were 17.9% (72) and 32.5% (127), respectively (P < 0.001). IS and
      GL identified 17 (4.2%) and 73 (18.1%) additional cases respectively when the
      other method failed to identify MTB. The combined yields (acid-fast bacilli
      positivity/MTB) with GL and IS on day 1 (115, 28.5%) were less than that obtained
      from 2 consecutive GL (135, 33.5%), but better than 2 consecutive IS samples (79,
      19.6%; P < 0.001). CONCLUSION: It is feasible to collect induced sputum and
      gastric lavage on an ambulatory basis. The yield of MTB obtained by GL is
      superior to that obtained by IS.

PMID- 23958818
TI  - Population pharmacokinetic modeling of hydromorphone in cardiac surgery patients
      during postoperative pain therapy.
AB  - BACKGROUND: Hydromorphone is a u-selective opioid agonist used in postoperative
      pain therapy. This study aimed to evaluate the pharmacokinetics of hydromorphone
      in cardiac surgery patients during postoperative analgesia with target-controlled
      infusion and patient-controlled analgesia. METHODS: In this study, 50 adult
      patients were enrolled to receive intravenous hydromorphone during postoperative
      pain therapy. Arterial plasma samples were collected for measurements of drug
      concentration. Population pharmacokinetic parameters were estimated using
      nonlinear mixed-effects modeling. Results were validated and simulations were
      carried out to evaluate results. RESULTS: Data from 49 patients (age range, 40-81
      yr) were analyzed. The pharmacokinetics of hydromorphone were best described by a
      three-compartment model. Age was incorporated as a significant covariate for
      elimination clearance and central volume of distribution. Scaling all parameters
      with body weight improved the model significantly. The final estimates of the
      model parameters for the typical adult patient (67 yr old, weighing 70 kg)
      undergoing cardiac surgery were as follows: CL1 = 1.01 l/min, V1 = 3.35 l, CL2 =
      1.47 l/min, V2 = 13.9 l, CL3 = 1.41 l/min, and V3 = 145 l. The elimination
      clearance decreased by 43% between the age of 40 and 80 yr, and simulations
      demonstrated that context-sensitive half-time increased from 26 to 84 min in 40-
      and 80-yr-old subjects, respectively. CONCLUSIONS: The final pharmacokinetic
      model gave a robust representation of hydromorphone pharmacokinetics. Inclusion
      of age and body weight to the model demonstrated a significant influence of these
      covariates on hydromorphone pharmacokinetics. The application of this patient
      derived population model in individualized pain therapy should improve the dosing
      of hydromorphone in patients undergoing cardiac surgery.

PMID- 23958821
TI  - Bone cysts after osteochondral allograft repair of cartilage defects in goats
      suggest abnormal interaction between subchondral bone and overlying synovial
      joint tissues.
AB  - The efficacy of osteochondral allografts (OCAs) may be affected by osseous
      support of the articular cartilage, and thus affected by bone healing and
      remodeling in the OCA and surrounding host. Bone cysts, and their communication
      pathways, may be present in various locations after OCA insertion and reflect
      distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage
      (FRESH, 4 degrees C/14d, 4 degrees C/28d, FROZEN) on cartilage quality in fifteen
      adult goats after 12months in vivo. The objectives of this study were to further
      analyze OCAs and contralateral non-operated (Non-Op) CONTROLS from the medial
      femoral condyle to (1) determine the effect of OCA storage on local subchondral
      bone (ScB) and trabecular bone (TB) structure, (2) characterize the location and
      structure of bone cysts and channels, and (3) assess the relationship between
      cartilage and bone properties. (1) Overall bone structure after OCAs was altered
      compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB
      roughening. ScB BV/TV in FROZEN OCAs was lower than Non-Op and other OCAs. TB
      BV/TV in FRESH, 4 degrees C/14d, and 4 degrees C/28d OCAs did not vary compared
      to Non-Op, but BS/TV was lower. (2) OCAs contained "basal" cysts, localized to
      deeper regions, some "subchondral" cysts, localized near the bone-cartilage
      interface, and some ScB channels. TB surrounding basal cysts exhibited higher
      BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with
      subchondral cysts and ScB channels, (c) with ScB channels, or (d) with
      subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage
      gross morphology was strongly associated with abnormal MUCT bone structure.
      Evidence of cartilage-bone communication following OCA repair may favor fluid
      intrusion as a mechanism for subchondral cyst formation, while bone resorption at
      the graft-host interface without affecting overall bone and cartilage structure
      may favor bony contusion mechanism for basal cyst formation. These findings
      suggest that cysts occurring after OCAs may result from aberrant mechanobiology
      due to (1) altered compartmentalization that normally separates overlying
      cartilage and subchondral bone, either from distinct ScB channels or more general
      ScB plate deterioration, and (2) bone resorption at the basal graft-host
      interface. 

PMID- 23958824
TI  - Buckyball-, carbon nanotube-, graphite-, and graphene-enhanced dehydrogenation of
      lithium aluminum hydride.
AB  - Compared to C60, carbon nanotubes, and graphite, graphene more effectively lowers
      the dehydrogenation temperature and improves the dehydrogenation kinetics of
      LiAlH4. With 15 wt% graphene incorporation, the initial hydrogen release
      temperature is ~80  degrees C (60  degrees C lower than that of pristine LiAlH4).

PMID- 23958822
TI  - Epiphyseal abnormalities, trabecular bone loss and articular chondrocyte
      hypertrophy develop in the long bones of postnatal Ext1-deficient mice.
AB  - Long bones are integral components of the limb skeleton. Recent studies have
      indicated that embryonic long bone development is altered by mutations in Ext
      genes and consequent heparan sulfate (HS) deficiency, possibly due to changes in
      activity and distribution of HS-binding/growth plate-associated signaling
      proteins. Here we asked whether Ext function is continuously required after birth
      to sustain growth plate function and long bone growth and organization. Compound
      transgenic Ext1(f/f);Col2CreERT mice were injected with tamoxifen at postnatal
      day 5 (P5) to ablate Ext1 in cartilage and monitored over time. The Ext1
      deficient mice exhibited growth retardation already by 2weeks post-injection, as
      did their long bones. Mutant growth plates displayed a severe disorganization of
      chondrocyte columnar organization, a shortened hypertrophic zone with low
      expression of collagen X and MMP-13, and reduced primary spongiosa accompanied,
      however, by increased numbers of TRAP-positive osteoclasts at the chondro-osseous
      border. The mutant epiphyses were abnormal as well. Formation of a secondary
      ossification center was significantly delayed but interestingly, hypertrophic
      like chondrocytes emerged within articular cartilage, similar to those often seen
      in osteoarthritic joints. Indeed, the cells displayed a large size and round
      shape, expressed collagen X and MMP-13 and were surrounded by an abundant
      Perlecan-rich pericellular matrix not seen in control articular chondrocytes. In
      addition, ectopic cartilaginous outgrowths developed on the lateral side of
      mutant growth plates over time that resembled exostotic characteristic of
      children with Hereditary Multiple Exostoses, a syndrome caused by Ext mutations
      and HS deficiency. In sum, the data do show that Ext1 is continuously required
      for postnatal growth and organization of long bones as well as their adjacent
      joints. Ext1 deficiency elicits defects that can occur in human skeletal
      conditions including trabecular bone loss, osteoarthritis and HME. 

PMID- 23958823
TI  - Association of lumbar disc degeneration with osteoporotic fractures; the
      Rotterdam study and meta-analysis from systematic review.
AB  - OBJECTIVE: To investigate the relation between lumbar disc degeneration (LDD) and
      all type of osteoporotic (OP) fractures including vertebral. METHODS: This study
      is part of the Rotterdam study, a large prospective population-based cohort study
      among men and women aged 55years and over. In 2819 participants spine radiographs
      were scored for LDD (osteophytes and disc space narrowing (DSN)) from L1 till S1,
      using the Lane atlas. Osteoporotic (OP) fracture data were collected and verified
      by specialists during 12.8years. We considered two types of vertebral fractures
      (VFx): Clinical VFx (symptomatic fractures recorded by medical practitioners) and
      Radiographic VFx (using the McCloskey-Kanis method). Meta-analysis of published
      studies reporting an association of LDD features and VFx was performed.
      Differences in Bone Mineral Density (BMD) between participants with and without
      LDD features were analyzed using ANOVA. Risk of OP-fractures was analyzed using
      Cox regression. RESULTS: In a total of 2385 participants, during 12.8years follow
      up, 558 suffered an OP-fracture. Subjects with LDD had an increased OP fracture
      risk compared to subjects without LDD (HR: 1.29, CI: 1.04-1.60). LDD-cases have
      between 0.3 and 0.72 standard deviations more BMD than non-cases in all analyzed
      regions including total body BMD and skull BMD (P<0.001). Only males with LDD had
      increased risk for OP-fractures compared to males without LDD (adjusted-HR: 1.80,
      95%CI: 1.20-2.70, P=0.005). The risk was also higher for VFx in males (HR: 1.64,
      CI: 1.03-2.60, P: 0.04). The association LDD-OP-fractures in females was lower
      and not significant (adjusted-HR: 1.08, 95%CI: 0.82-1.41). Meta-analyses showed
      that the risk of VFx in subjects with LDD has been studied only in women and
      there is not enough evidence to confidently analyze the relationship between LDD
      features (DSN or/and OPH) and VFx due to low power and heterogeneity in phenotype
      definition in the collected studies. CONCLUSIONS: Male subjects with LDD have a
      higher osteoporotic fracture risk, in spite of systemically higher BMD.

PMID- 23958826
TI  - On the stability of cationic complexes of neon with helium--solving an
      experimental discrepancy.
AB  - Helium nanodroplets are doped with neon and ionized by electrons. The size
      dependence of the ion abundance of HenNex(+), identified in high-resolution mass
      spectra, is deduced for complexes containing up to seven neon atoms and dozens of
      helium atoms. Particularly stable ions are inferred from anomalies in the
      abundance distributions. Two pronounced anomalies at n = 11 and 13 in the
      HenNe(+) series confirm drift-tube data reported by Kojima et al. [T. M. Kojima
      et al., Z. Phys. D, 1992, 22, 645]. The discrepancy with previously published
      spectra of neon-doped helium droplets, which did not reveal any abundance
      anomalies [T. Ruchti et al., J. Chem. Phys., 1998, 109, 10679-10687; C. A.
      Brindle et al., J. Chem. Phys., 2005, 123, 064312], is most likely due to limited
      mass resolution, which precluded unambiguous analysis of contributions from
      different ions with identical nominal mass. However, calculated dissociation
      energies of HenNe(+) reported so far do not correlate with the present data,
      possibly because of challenges in correctly treating the linear, asymmetric [He
      Ne-He](+) ionic core in HenNe(+). Anomalies identified in the distributions of
      HenNex(+) for x > 1, including prominent ones at He12Ne2(+) and He14Ne2(+), may
      help to better understand solvation of Ne(+) and Nex(+) in helium. 

PMID- 23958825
TI  - The holistic worldview in action: evolution of holistic nurses certification
      programs.
AB  - The American Holistic Nurses Credentialing Corporation (AHNCC), the only national
      credentialing body for holistic nurses, has a responsibility to offer valid,
      reliable, and rigorous certification examinations and to grow and evolve as
      indicated by social and professional changes. This article describes four major
      changes in the work of AHNCC since 2004: a detection of an evolution in the
      domain of holistic nursing through review of the literature; clarification and
      specification of levels of practice by educational level; development of the
      nurse coach role in nursing, designed within the precepts of holistic nursing;
      and AHNCC's response to the social paradigm shift for health care, and nursing's
      advanced practice registered nurse consensus model. Each of these is discussed in
      detail describing the circumstances that perpetuated AHNCC's consideration and
      the actions taken by AHNCC. 

PMID- 23958827
TI  - Delayed onset of vastii muscle activity in response to rapid postural
      perturbations following eccentric exercise: a mechanism that underpins knee pain
      after eccentric exercise?
AB  - BACKGROUND: Appropriate timing of activity of the vastus medialis obliqus (VMO)
      and vastus lateralis (VL) muscles is a key factor for proper tracking of the
      patella in the trochlear groove during knee extension. This study investigates
      the relative timing of activation of the VMO and VL muscles during unexpected
      perturbations performed before and after eccentric exercise. METHODS: Surface
      electromyography signals were recorded from the VMO and VL muscles of the right
      leg in 11 healthy men during rapid postural perturbations performed at baseline,
      immediately after eccentric exercise of the quadriceps, and at 24 and 48 h after
      exercise. Participants stood on a moveable platform during which eight randomised
      postural perturbations were performed (4 repetitions of 2 perturbation types: 8
      cm forward slides, 8 cm backward slides). RESULTS: Before the eccentric exercise,
      the onset of VMO activity was significantly earlier than the VL muscle (average
      for both forward and backward perturbations: VMO 39.0+/-7.1 ms; VL 43.7+/-7.9
      ms). However, the onset of VMO activity was significantly later compared with VL
      muscle immediately after eccentric exercise and this remained 24 and 48 h after
      eccentric exercise (average across all postexercise sessions and perturbation
      directions: VMO 72.3+/-11.1 ms; VL 56.0+/-8.2 ms; p<0.05). CONCLUSIONS: The onset
      of VMO-VL activity in response to rapid destabilising perturbations is altered
      immediately after eccentric exercise and during eccentric exercise-induced muscle
      soreness up to 48 h later. These observations may help explain the high
      prevalence of knee disorders after high intensity eccentric exercise.

PMID- 23958828
TI  - Mild to moderate postnatal hydronephrosis--grading systems and management.
AB  - No universal guidelines exist for the management of patients with mild to
      moderate antenatal hydronephrosis (ANH). Unsurprisingly, practice patterns vary
      considerably with respect to recommendations for postnatal evaluation and follow
      up imaging schedule. Although some clinical tools are available to specifically
      grade ANH and postnatal hydronephrosis, these are commonly used interchangeably
      with varying degrees of success. A universal classification system and
      nomenclature are needed to best identify patients at risk of renal deterioration,
      UTI and need for surgical intervention. We present our own approach to postnatal
      risk stratification and management, including recommendations regarding serial
      ultrasonography schedule, prophylactic antibiotics, voiding cystourethrogram and
      renal scintigraphy. 

PMID- 23958829
TI  - Bladder cancer: Gaps in staging and care identified.

PMID- 23958830
TI  - Clinical trials: Combination therapy effective for treating male storage
      symptoms.

PMID- 23958831
TI  - 3D simulation of pelvic system numerical simulation for a better understanding of
      the contribution of the uterine ligaments.
AB  - INTRODUCTION AND HYPOTHESIS: Genital prolapse remains a complex pathological
      condition. Physiopathology remains poorly understood, aetiology is multi
      factorial, surgery is not always satisfying, as the rate of relapse cannot be
      overlooked. More over a good anatomical result will not always guarantee
      functional satisfaction. The aim of our study is to have a better understanding
      of the involvement of uterine ligaments in pelvic statics via 3D simulation.
      METHODS: Simulation of pelvic mobility is performed with a validated numerical
      model in a normal situation (standing up to lying down) or induced pathological
      ones where parts of the constitutive elements of the model are virtually "cut"
      independently. Displacements are then discussed. RESULTS: Numerical results have
      been compared with dynamic MRI for two volunteers. Dynamic sequences had 90
      images, and 180 simulations have been validated. Results are coherent with
      clinical data and the literature, thus validating our mechanical approach.
      Uterine ligaments are involved in pelvic statics, but their lesions are not
      sufficient to generate a genital prolapse. Round ligaments play a part in uterine
      orientation; the utero-sacral ligaments support the uterus when standing up.
      CONCLUSIONS: Pelvic normal and pathological mobility study via modelling and 3D
      simulation is a new strategy in understanding the complex multifactorial
      physiopathology of genital prolapse. This approach must be validated in a larger
      series of patients. Nevertheless, pelvic ligaments seem to play an important role
      in statics, especially, in agreement with a literature survey, utero-sacral
      ligaments in a standing position.

PMID- 23958832
TI  - Acute urinary retention caused by OVHIRA syndrome.
AB  - Obstructed hemivagina and ipsilateral renal anomaly (OVHIRA) syndrome is a
      congenital urogenital malformation that associates a bifid uterus with a
      longitudinal vaginal septum, resulting in a blind hemivagina and an ipsilateral
      renal agenesis. The clinical presentation is highly variable, delaying diagnosis
      and leading to important complications. An 18-year-old woman was diagnosed with
      OVHIRA syndrome following acute urinary retention. An agenesis in the left-sided
      renal system and an enormous pelvic mass compressing the adjacent structures were
      revealed in the intravenous urography. Nuclear magnetic resonance was the imaging
      modality that provided most diagnostic information, defining the pelvic mass as a
      giant left hematometrocolpos contained with a longitudinal vaginal septum.
      Resection of the septum was performed draining all reduced hematic content and
      both hemiuteri communicated with a single vagina, resulting in an asymptomatic
      patient. OVHIRA syndrome is a little known entity that can occur atypically,
      which makes the diagnosis difficult and delays the treatment. It is important to
      maintain a high degree of clinical suspicion to avoid irreversible complications.

PMID- 23958833
TI  - Effect of cyclic loading on the nanoscale deformation of hydroxyapatite and
      collagen fibrils in bovine bone.
AB  - Cyclic compressive loading tests were carried out on bovine femoral bones at body
      temperature (37  degrees C), with varying mean stresses (-55 to -80 MPa) and
      loading frequencies (0.5-5 Hz). At various times, the cyclic loading was
      interrupted to carry out high-energy X-ray scattering measurements of the
      internal strains developing in the hydroxyapatite (HAP) platelets and the
      collagen fibrils. The residual strains upon unloading were always tensile in the
      HAP and compressive in the fibrils, and each increases in magnitude with loading
      cycles, which can be explained from damage at the HAP-collagen interface and
      accumulation of plastic deformation within the collagen phase. The samples tested
      at a higher mean stress and stress amplitude, and at lower loading frequencies
      exhibit greater plastic deformation and damage accumulation, which is attributed
      to greater contribution of creep. Synchrotron microcomputed tomography of some of
      the specimens showed that cracks are produced during cyclic loading and that they
      mostly occur concentric with Haversian canals.

PMID- 23958835
TI  - [Young patient with acute monolateral amaurosis].
AB  - A 39-year-old patient presented with acute visual loss of the left eye. Although
      the initial ophthalmological and neurological examinations were uneventful,
      magnetic resonance imaging (MRI) showed optic canal narrowing and compression of
      the optic nerve secondary to a prominent posteriorly misplaced ethmoidal cell (so
      called Onodi cell). Endonasal ethmoidectomy with decompression of the infected
      Onodi cell was performed. Microbiological testing showed growth of Haemophilus
      influenzae. Despite early surgical intervention vision could not be restored. 

PMID- 23958836
TI  - [Supraciliary microstent for open-angle glaucoma: clinical results of a
      prospective multicenter study].
AB  - PURPOSE: The suprachoroidal CyPass micro-stent is designed to be implanted into
      the supraciliary space to facilitate aqueous outflow along the uveoscleral
      pathway in patients with open-angle glaucoma (OAG). This study assessed the
      safety of micro-stent implantation in patients undergoing cataract surgery.
      METHODS: In this multicenter study the CyPass microstent was implanted in
      patients with OAG undergoing cataract surgery. The implantation was performed
      using a minimally invasive, conjunctiva-sparing, ab interno intervention. Primary
      endpoints were safety aspects of the implant, secondary endpoints were the
      reduction of intraocular pressure (IOP) and topical medication. RESULTS: There
      were no severe adverse events during or after surgery in any of the patients. In
      patients with controlled glaucoma (IOP < 21 mmHg) the average IOP remained
      constant throughout the 24 month follow-up period but mean medication use
      decreased from 2.0 at baseline to 1.1 postoperative. In patients with IOP of >=
      21 mmHg the pressure was reduced by 37 % postoperatively and mean medication
      decreased from 2.2 at baseline to 1.0. CONCLUSIONS: The safety profile of
      combined cataract surgery and CyPass microstent implantation is acceptable and
      patients also showed a decrease in IOP and medication use.

PMID- 23958837
TI  - [Disseminated retinal "blemish". Spontaneous - with no further signs of
      inflammation].

PMID- 23958838
TI  - [Inverted pseudohypopyon in degenerative myopia.]

PMID- 23958839
TI  - Tunable SERS using gold nanoaggregates on an elastomeric substrate.
AB  - We report on the self-assembly of colloidal gold nanoparticles on a stretchable,
      elastomeric membrane, and the use of this membrane as a base substrate for far
      field confocal Raman measurements. Surface-enhanced Raman scattering (SERS)
      enhancement for such a substrate was estimated as 10(6) to 10(7). Atomic force
      microscopy has been used to study the changes in nanoparticle topography when the
      membrane is stretched. The homogeneous strain defined by average relative motion
      of nanoparticles is approximately half the macroscopically-applied biaxial
      strain. The SERS intensity was maximized when the membrane was at rest (i.e.
      without stretch), and reduced as stretching was increased. Our measurements are
      consistent with theoretical and numerical SERS enhancements for the interstitial
      gap between two spheres. The data indicate that the resting gap between the
      spheres is 11 nm or 16 nm, using two theoretical models. This work represents
      progress towards particularly facile sample fabrication and in situ tuning
      techniques for SERS. 

PMID- 23958841
TI  - Postpartum reversibility of impaired incretin effect in gestational diabetes
      mellitus.
AB  - The potential reversibility of a reduced incretin effect is unclear. We
      investigated the incretin effect during third trimester and 3 to 4months
      postpartum in women with and without gestational diabetes mellitus (GDM). Ten
      women with GDM (plasma glucose (PG) concentration at 120min after 75g-oral
      glucose tolerance test (OGTT) (PG120min): 10.1+/-0.6mmol/l (mean+/-SEM)) and
      eight women with normal glucose tolerance (NGT; PG120min: 7.0+/-0.1mmol/l) were
      investigated on four occasions: 4h 50g-OGTT and isoglycaemic intravenous glucose
      infusion during third trimester and 3 to 4months postpartum. In women with GDM,
      the incretin effect increased significantly postpartum (31+/-6 vs. 56+/-6%,
      p=0.02), whereas the increment in women with NGT was insignificant (35+/-12 vs.
      56+/-9%, p=0.08). Similarly, the gastrointestinal-mediated glucose disposal
      (GIGD=100%*(glucoseOGTT-glucoseIIGI)/glucoseOGTT) was reduced to diabetic levels
      in women with GDM (37+/-3%), but increased (p=0.030) to normal levels post partum
      (58+/-6%). GIGD did not change significantly in NGT women (48+/-3 vs. 57+/-6%,
      p=0.94). Women with GDM exhibit a reduced incretin effect which is fully
      reversible alongside the restoration of normal glucose homeostasis, whereas the
      reduction in incretin effect during pregnancy in women with NGT was
      insignificant. Our results suggest that decreased incretin effect in women with
      GDM is a fully reversible phenomenon. 

PMID- 23958842
TI  - Fundus autofluorescence patterns in primary intraocular lymphoma.
AB  - PURPOSE: To evaluate fundus autofluorescence (FAF) patterns in patients with
      primary intraocular (vitreoretinal) lymphoma. METHODS: Records of all patients
      with primary intraocular lymphoma who underwent FAF imaging at the National Eye
      Institute were reviewed. Fundus autofluorescence patterns were evaluated with
      respect to clinical disease status and the findings on fluorescein angiography
      and spectral-domain optical coherence tomography. RESULTS: There were 18 eyes (10
      patients) with primary intraocular lymphoma that underwent FAF imaging. Abnormal
      autofluorescence in the form of granular hyperautofluorescence and
      hypoautofluorescence was seen in 11 eyes (61%), and blockage by mass lesion was
      seen in 2 eyes (11%). All eyes with granular pattern on FAF had active primary
      intraocular lymphoma at the time of imaging, but there were 5 eyes with
      unremarkable FAF, which were found to have active lymphoma. The most common
      pattern on fluorescein angiography was hypofluorescent round spots with a
      "leopard spot" appearance (43%). These hypofluorescent spots on fluorescein
      angiography correlated with hyperautofluorescent spots on FAF in 5 eyes (36%)
      (inversion of FAF). Nodular hyperreflective spots at the level of retinal pigment
      epithelium on optical coherence tomography were noted in 43% of eyes. The
      hyperautofluorescent spots on FAF correlated with nodular hyperreflective spots
      on optical coherence tomography in 6 eyes (43%). CONCLUSION: Granularity on FAF
      was associated with active lymphoma in majority of the cases. An inversion of FAF
      (hyperautofluorescent spots on FAF corresponding to hypofluorescent spots on
      fluorescein angiography) was observed in less than half of the eyes.

PMID- 23958840
TI  - Keratinocytes express cytokines and nerve growth factor in response to
      neuropeptide activation of the ERK1/2 and JNK MAPK transcription pathways.
AB  - Sensory neurons innervating the skin can release neuropeptides that are believed
      to modulate cellular proliferation, wound healing, pigmentation, and keratinocyte
      innate immune responses. While the ability of neuropeptides to stimulate
      keratinocyte production of inflammatory mediators has been demonstrated, there is
      no information concerning the mechanisms by which neuropeptide activation of
      keratinocyte cell surface receptors ultimately leads to the up-regulation of
      mediator production. In this study we used a keratinocyte cell line to identify
      the presence of substance P (SP) and calcitonin gene-related peptide (CGRP)
      receptors on keratinocytes and examined the effects of SP and CGRP stimulation on
      keratinocyte neuropeptide signaling, cell proliferation, and interleukin-1beta
      (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and
      nerve growth factor (NGF) expression. Neuropeptide stimulation caused an up
      regulation of neuropeptide receptor expression in keratinocytes and a dramatic
      increase in keratinocyte secretion of SP and CGRP, suggesting possible autocrine
      or paracrine stimulatory effects and amplification of neuropeptide signaling.
      Both SP and CGRP concentration-dependently stimulated cellular proliferation and
      the expression and secretion of inflammatory cytokines and NGF in keratinocytes.
      SP also activated all 3 families of mitogen activated protein kinase (MAPK) and
      nuclear factor kappaB (NFkappaB) in keratinocytes, while CGRP only activated p38
      and extracellular signal related kinase1/2 (ERK1/2) MAPKs. Neuropeptide
      stimulated inflammatory mediatory production in keratinocytes was reversed by
      ERK1/2 and JNK inhibitors. The current study is the first to observe; 1) that
      CGRP stimulates keratinocyte expression of CGRP and its receptor complex, 2) that
      SP and CGRP stimulate IL-6 and TNF-alpha secretion in keratinocytes, 3) that SP
      activated all three MAPK families and the NFkappaB transcriptional signaling
      pathway in keratinocytes, and 4) that SP and CGRP stimulated inflammatory
      mediator production in keratinocytes is dependent on ERK1/2 and JNK activation.
      These studies provide evidence suggesting that disruption of ERK1/2 and JNK
      signaling may potentially be an effective therapy for inflammatory skin diseases
      and pain syndromes mediated by exaggerated sensory neuron-keratinocyte signaling.

PMID- 23958843
TI  - Assessment of vision-related quality of life in patients with central retinal
      artery occlusion.
AB  - BACKGROUND: Central retinal artery occlusion (CRAO) is a major cause for severe
      visual impairment. Its effect on vision-related quality of life has not yet been
      determined. The purpose of the present study was thus to assess vision-related
      quality of life in patients with CRAO using the 39-item National Eye Institute
      Visual Function Questionnaire. METHODS: The case-control study comprised 26
      patients with unilateral CRAO and a control group consisting of 26 control
      subjects, matched for age and sex. Vision-related quality of life was measured
      using the 39-item National Eye Institute Visual Function Questionnaire. RESULTS:
      After Bonferroni correction, the median 39-item National Eye Institute Visual
      Function Questionnaire composite score was significantly lower in patients with
      CRAO than in those in the control group (P(corr) < 0.001). Patients with CRAO
      showed significantly lower median scores in 9 of 12 subscales: general vision
      (P(corr) < 0.001), peripheral vision (P(corr) < 0.001), difficulties with near
      vision activities (P(corr) < 0.001), difficulties with distance-vision activities
      (P(corr) < 0.001), role difficulties as a result of vision problems (P(corr) <
      0.001), dependency on others because of vision problems (P(corr) < 0.001),
      limitations in social functioning because of vision problems (P(corr) < 0.001),
      mental health symptoms because of vision problems (P(corr) < 0.001), and general
      health (P(corr) = 0.008). CONCLUSION: Our data suggest that vision-related
      quality of life is reduced in patients with CRAO.

PMID- 23958844
TI  - Sectoral retinal nerve fiber layer thinning in branch retinal vein occlusion.
AB  - PURPOSE: To analyze longitudinal changes in the retinal nerve fiber layer (RNFL)
      thickness in branch retinal vein occlusion (BRVO) using optical coherence
      tomography. METHODS: The authors prospectively analyzed 20 eyes in 20 patients
      diagnosed with branch retinal vein occlusion (BRVO) and followed for more than 1
      year. The RNFL thickness of the normal and occluded eyes was measured at the time
      of diagnosis and at 1, 3, 6, and 12 months. The authors compared the changes in
      the occluded eye over the follow-up and the differences between two eyes at each
      time. They also analyzed the area opposite the occluded area. RESULTS: The
      thickness of the RNFL in BRVO was significantly reduced at 1, 3, 6, and 12 months
      (P = 0.005 at 1 month and P = 0.001 at 3, 6, and 12 months) compared with initial
      thickness. The RNFL thickness at 3 months did not differ significantly between 2
      eyes, whereas at 6 months and 12 months, significant (P = 0.032, P = 0.002,
      respectively.) thinning was observed in the occluded eye. Analysis of the area
      opposite that of BRVO revealed no significant (P > 0.05) change during the follow
      up and no difference between the 2 eyes. CONCLUSION: There was a significant
      decrease in RNFL thickness over time in BRVO and significant thinning at 6 months
      compared with the normal eye. Retinal nerve fiber layer thinning needs to be
      differentiated from glaucoma or systemic disease, but it should be considered the
      natural course after BRVO.

PMID- 23958845
TI  - Tuning nanopore surface polarity and rectification properties through enzymatic
      hydrolysis inside nanoconfined geometries.
AB  - Enzyme-catalyzed reactions inside nanoconfined geometries promote sensitive
      changes in the surface charge polarity and the concomitant permselective
      transport properties of the single conical nanopores. 

PMID- 23958846
TI  - Diagnosing diabetes mellitus: performance of hemoglobin A1c point-of-care
      instruments in general practice offices.
AB  - BACKGROUND: Hemoglobin A1c (Hb A1c) measurement by hospital laboratory
      instruments, but not by point-of-care (POC) instruments, has been recommended for
      use to diagnose diabetes mellitus. We evaluated results from 13 Hb A1c external
      quality assurance (EQA) surveys over a 6-year period in Norway, from both POC
      instruments used in general practice (GP) offices and instruments in hospital
      laboratories, against the analytical quality specifications recommended for use
      of Hb A1c to diagnose diabetes mellitus. METHODS: All GP offices (n = 1288) and
      hospital laboratories (n = 52) measuring Hb A1c in Norway participated in the EQA
      survey. The percentage of participants that performed measurements within the
      quality specifications was calculated. Pooled within-laboratory CVs were
      estimated for the Afinion, DCA 2000, DCA 2000+, DCA Vantage(TM), and Nycocard Hb
      A1c Reader instruments and for hospital laboratory instruments. RESULTS: Between
      60% to 90% of Afinion and DCA users and hospital laboratories performed Hb A1c
      measurements within the quality specifications for both trueness (6.0%) and
      imprecision (CV <=2.0%) at 2 levels in each EQA survey. The pooled within
      laboratory CVs for the Afinion and DCA instruments and hospital laboratories were
      below the recommended limit of 2.0% for most of the surveys. CONCLUSIONS: A large
      proportion of GP offices using Afinion and DCA POC instruments to measure Hb A1c
      fulfill the analytical quality specifications for diagnosing diabetes mellitus,
      and these instruments demonstrate analytical quality comparable to that of
      hospital laboratory instruments. When GP offices participate in a stringent
      quality assurance program and generate Hb A1c measurements that meet analytical
      quality specifications, these measurements can be recommended for use to diagnose
      diabetes mellitus.

PMID- 23958847
TI  - MicroRNA signature helps distinguish early from late biochemical failure in
      prostate cancer.
AB  - PURPOSE: Prostate-specific antigen testing has led to overtreatment of prostate
      cancer (PCa). Only a small subset of PCa patients will have an aggressive disease
      that requires intensive therapy, and there is currently no biomarker to predict
      disease aggressiveness at the time of surgery. MicroRNAs (miRNAs) are reported to
      be involved in PCa pathogenesis. METHODS: This study involved 105 participants.
      For the discovery phase, prostatectomy samples were dichotomized to high-risk (n
      = 27, biochemical failure <36 months after prostatectomy) and low-risk groups (n
      = 14, >= 36 months without biochemical failure). Expression of 754 mature miRNAs
      was compared between the 2 groups. Linear regression models were built to
      accurately predict biochemical failure risk. miRNA mimics were transfected into
      PCa model cell lines to test effects on proliferation and to deduce responding
      signaling pathways. RESULTS: We identified 25 differentially expressed miRNAs
      between the biochemical failure risk groups. Based on the expression of 2-3
      miRNAs, 3 logistic regression models were developed, each with a high positive
      predictive value. Candidate miRNAs and the best-performing model were also
      verified on an independent PCa set. miRNA-152, featured in the models, was
      further investigated by using cell line models and was shown to affect cell
      proliferation. Predicted interaction between miR-152 and (mRNA)ERBB3
      (erythroblastic leukemia viral oncogene homolog 3) was experimentally validated
      in vitro. CONCLUSIONS: miRNAs can help to predict biochemical failure risk at the
      time of prostatectomy.

PMID- 23958848
TI  - Biomarkers for acute kidney injury: where are we today? Where should we go?

PMID- 23958849
TI  - Synthesis and electrocatalytic properties of tetrahexahedral, polyhedral, and
      branched Pd@Au core-shell nanocrystals.
AB  - Tetrahexahedral, polyhedral, and branched Pd@Au core-shell nanostructures were
      selectively produced by manipulating their growth thermodynamics and kinetics.
      The current density in the electrochemical oxidation of H2O2 and the
      electrochemiluminescence density of luminol-H2O2 systems at the tetrahexahedron
      modified electrode are 43.5 and 16.4 times that at the bulk Au electrode,
      respectively. 

PMID- 23958850
TI  - Similar neuroprotective effects of ischemic and hypoxic preconditioning on
      hypoxia-ischemia in the neonatal rat: a proton MRS study.
AB  - The aim of this study was to evaluate the effect of ischemic and hypoxic
      preconditioning on hypoxia-ischemia (HI) in the neonatal rat. Seven-day-old
      Sprague-Dawley rats were divided into four groups: control, sham, ischemic
      preconditioning, and hypoxic preconditioning. Ischemic preconditioning with a 10
      min occlusion of the right carotid artery and hypoxic preconditioning with 4-h of
      hypoxia (8% oxygen) were performed 24-h before HI. For HI, all rats underwent
      right carotid artery ligature, followed by 2.5-h of hypoxia. Proton magnetic
      resonance spectroscopy ((1)H MRS) and TUNEL staining were evaluated at 1 and 7
      days after HI. At 2 weeks after HI, all rats were sacrificed for morphological
      analysis. The lipid (Lip), N-acetyl aspartate (NAA), creatine (Cr), and choline
      ratios were calculated and compared with TUNEL staining and brain morphologies.
      Both the ischemic and hypoxic preconditioning groups showed lower Lip/NAA and
      Lip/Cr ratios and morphological scores, and fewer TUNEL-positive cells than the
      control and sham groups (P < 0.05). There were no significant differences between
      the two preconditioning groups. In addition, the ratios correlated with the TUNEL
      staining and the degrees of morphological changes in all of the groups (P <
      0.05). These results suggest that ischemic and hypoxic preconditioning in
      neonatal rats with HI similarly attenuate brain injury. Moreover, Lip/NAA and
      Lip/Cr ratios may be used as markers for assessing the extent of brain damage.

PMID- 23958851
TI  - Quality of discharge practices and patient understanding at an academic medical
      center.
AB  - IMPORTANCE: With growing national focus on reducing readmissions, there is a need
      to comprehensively assess the quality of transitional care, including discharge
      practices, patient perspectives, and patient understanding. OBJECTIVE: To conduct
      a multifaceted evaluation of transitional care from a patient-centered
      perspective. DESIGN: Prospective observational cohort study, May 2009 through
      April 2010. SETTING: Urban, academic medical center. PARTICIPANTS: Patients 65
      years and older discharged home after hospitalization for acute coronary
      syndrome, heart failure, or pneumonia. MAIN OUTCOMES AND MEASURES: Discharge
      practices, including presence of follow-up appointment and patient-friendly
      discharge instructions; patient understanding of diagnosis and follow-up
      appointment; and patient perceptions of and satisfaction with discharge care.
      RESULTS: The 395 enrolled patients (66.7% of those eligible) had a mean age of
      77.2 years. Although 349 patients (95.6%) reported understanding the reason they
      had been in the hospital, only 218 patients (59.6%) were able to accurately
      describe their diagnosis in postdischarge interviews. Discharge instructions
      routinely included symptoms to watch out for (98.4%), activity instructions
      (97.3%), and diet advice (89.7%) in lay language; however, 99 written reasons for
      hospitalization (26.3%) did not use language likely to be intelligible to
      patients. Of the 123 patients (32.6%) discharged with a scheduled primary care or
      cardiology appointment, 54 (43.9%) accurately recalled details of either
      appointment. During postdischarge interviews, 118 patients (30.0%) reported
      receiving less than 1 day's advance notice of discharge, and 246 (66.1%) reported
      that staff asked whether they would have the support they needed at home before
      discharge. CONCLUSIONS AND RELEVANCE: Patient perceptions of discharge care
      quality and self-rated understanding were high, and written discharge
      instructions were generally comprehensive although not consistently clear.
      However, follow-up appointments and advance discharge planning were deficient,
      and patient understanding of key aspects of postdischarge care was poor. Patient
      perceptions and written documentation do not adequately reflect patient
      understanding of discharge care.

PMID- 23958853
TI  - NeuroD1 regulation of migration accompanies the differential sensitivity of
      neuroendocrine carcinomas to TrkB inhibition.
AB  - The developmental transcription factor NeuroD1 is anomalously expressed in a
      subset of aggressive neuroendocrine tumors. Previously, we demonstrated that TrkB
      and neural cell adhesion molecule (NCAM) are downstream targets of NeuroD1 that
      contribute to the actions of neurogenic differentiation 1 (NeuroD1) in
      neuroendocrine lung. We found that several malignant melanoma and prostate cell
      lines express NeuroD1 and TrkB. Inhibition of TrkB activity decreased invasion in
      several neuroendocrine pigmented melanoma but not in prostate cell lines. We also
      found that loss of the tumor suppressor p53 increased NeuroD1 expression in
      normal human bronchial epithelial cells and cancer cells with neuroendocrine
      features. Although we found that a major mechanism of action of NeuroD1 is by the
      regulation of TrkB, effective targeting of TrkB to inhibit invasion may depend on
      the cell of origin. These findings suggest that NeuroD1 is a lineage-dependent
      oncogene acting through its downstream target, TrkB, across multiple cancer
      types, which may provide new insights into the pathogenesis of neuroendocrine
      cancers. 

PMID- 23958854
TI  - Deubiquitination of Dishevelled by Usp14 is required for Wnt signaling.
AB  - Dishevelled (Dvl) is a key regulator of Wnt signaling both in the canonical and
      non-canonical pathways. Here we report the identification of a regulatory domain
      of ubiquitination (RDU) in the C-terminus of Dvl. Mutations in the RDU resulted
      in accumulation of polyubiquitinated forms of Dvl, which were mainly K63 linked.
      Small interfering RNA-based screening identified Usp14 as a mediator of Dvl
      deubiquitination. Genetic and chemical suppression of Usp14 activity caused an
      increase in Dvl polyubiquitination and significantly impaired downstream Wnt
      signaling. These data suggest that Usp14 functions as a positive regulator of the
      Wnt signaling pathway. Consistently, tissue microarray analysis of colon cancer
      revealed a strong correlation between the levels of Usp14 and beta-catenin, which
      suggests an oncogenic role for Usp14 via enhancement of Wnt/beta-catenin
      signaling. 

PMID- 23958856
TI  - Ejection of a rear facing, golf cart passenger.
AB  - The following report details the findings of a series of experiments and
      simulations performed on a commercially available, shuttle style golf cart during
      several maneuvers involving rapid accelerations of the vehicle. It is determined
      that the current set of passive restraints on these types of golf carts are not
      adequate in preventing ejection of a rear facing passenger during rapid
      accelerations in the forward and lateral directions. Experimental data and
      simulations show that a hip restraint must be a minimum of 13 in. above the seat
      in order to secure a rear facing passenger during sharp turns, compared to the
      current restraint height of 5 in. Furthermore, it is determined that a restraint
      directly in front of the rear facing passenger is necessary to prevent ejection.
      In addressing these issues, golf cart manufacturers could greatly reduce the
      likelihood of injury due to ejection of a rear facing, golf cart passenger.

PMID- 23958855
TI  - Binding of alphavbeta1 and alphavbeta6 integrins to tenascin-C induces epithelial
      mesenchymal transition-like change of breast cancer cells.
AB  - Tenascin-C (TNC), a large hexameric extracellular glycoprotein, is a pleiotropic
      molecule with multiple domains binding to a variety of receptors mediating a wide
      range of cellular functions. We earlier reported that TNC induces epithelial
      mesenchymal transition (EMT)-like change in breast cancer cells. In the present
      study, we clarified TNC receptor involvement in this process. Among integrins
      previously reported as TNC receptors, substantial expression of alphav, alpha2,
      beta1 and beta6 subunits was detected by quantitative PCR and immunoblotting in
      MCF-7 cells. Integrin beta6 mRNA was remarkably upregulated by transforming
      growth factor (TGF)-beta1 treatment, and protein expression was prominently
      increased by additional exposure to TNC. Immunofluorescent labeling demonstrated
      integrin alphavbeta6 accumulation in focal adhesions after TNC treatment,
      especially in combination with TGF-beta1. The alpha2 and beta1 subunits were
      mainly localized at cell-cell contacts, alphav being found near cell cluster
      surfaces. Immunoprecipitation showed increase in alphavbeta1 heterodimers, but
      not alpha2beta1, after TNC treatment. Activated beta1 subunits detected by an
      antibody against the Ca(2+)-dependent epitope colocalized with alphav in focal
      adhesion complexes, associated with FAK phosphorylation at tyrosine 925.
      Neutralizing antibodies against alphav and beta1 blocked EMT-like change caused
      by TNC alone. In addition, anti-alphav and combined treatment with anti-beta1 and
      anti-alphavbeta6 inhibited TGF-beta1/TNC-induced EMT, whereas either of these
      alone did not. Integrin subunits alphav, beta1 and beta6, but not alpha2, bound
      to TNC immobilized on agarose beads in a divalent cation-dependent manner.
      Treatments with neutralizing antibodies against beta1 and alphavbeta6 reduced
      alphav subunit bound to the beads. Immunohistochemistry of these receptors in
      human breast cancer tissues demonstrated frequent expression of beta6 subunits in
      cancer cells forming scattered nests localized in TNC-rich stroma. These findings
      provide direct evidence that binding of alphavbeta6 and alphavbeta1 integrins to
      TNC as their essential ligand induces EMT-like change in breast cancer cells. 

PMID- 23958857
TI  - Single-molecule photon-fueled DNA nanoscissors for DNA cleavage based on the
      regulation of substrate binding affinity by azobenzene.
AB  - A pair of single-molecule photo-responsive DNA nanoscissors for DNA cleavage
      based on the regulation of substrate binding affinity was designed and
      fabricated. Compared with other DNA nanomachines, our DNA nanoscissors have the
      advantages of a clean switching mechanism, as well as robust and highly
      reversible operation. 

PMID- 23958859
TI  - Chemically activated formation of organic acids in reactions of the Criegee
      intermediate with aldehydes and ketones.
AB  - Reactions of the Criegee intermediate (CI, CH2OO) are important in atmospheric
      ozonolysis models. In this work, we compute the rates for reactions between CH2OO
      and HCHO, CH3CHO and CH3COCH3 leading to the formation of secondary ozonides
      (SOZ) and organic acids. Relative to infinitely separated reactants, the SOZ in
      all three cases is found to be 48-51 kcal mol(-1) lower in energy, formed via 1,3
      cycloaddition of CH2OO across the C=O bond. The lowest energy pathway found for
      SOZ decomposition is intramolecular disproportionation of the singlet biradical
      intermediate formed from cleavage of the O-O bond to form hydroxyalkyl esters.
      These hydroxyalkyl esters undergo concerted decomposition providing a low energy
      pathway from SOZ to acids. Geometries and frequencies of all stationary points
      were obtained using the B3LYP/MG3S DFT model chemistry, and energies were refined
      using RCCSD(T)-F12a/cc-pVTZ-F12 single-point calculations. RRKM calculations were
      used to obtain microcanonical rate coefficients (k(E)) and the reservoir state
      method was used to obtain temperature and pressure dependent rate coefficients
      (k(T, P)) and product branching ratios. At atmospheric pressure, the yield of
      collisionally stabilized SOZ was found to increase in the order HCHO < CH3CHO <
      CH3COCH3 (the highest yield being 10(-4) times lower than the initial CH2OO
      concentration). At low pressures, chemically activated formation of organic acids
      (formic acid in the case of HCHO and CH3COCH3, formic and acetic acid in the case
      of CH3CHO) was found to be the major product channel in agreement with recent
      direct measurements. Collisional energy transfer parameters and the barrier
      heights for SOZ reactions were found to be the most sensitive parameters
      determining SOZ and organic acid yield.

PMID- 23958858
TI  - Avoidance conditioning in bamboo sharks (Chiloscyllium griseum and C. punctatum):
      behavioral and neuroanatomical aspects.
AB  - Animals face different threats; to survive, they have to anticipate how to react
      or how to avoid these. It has already been shown in teleosts that selected
      regions in the telencephalon, i.e., the medial pallium, are involved in avoidance
      learning strategies. No such study exists for any chondrichthyan. In nature, an
      avoidance reaction may vary, ranging from a 'freeze' reaction to a startling
      response and quick escape. This study investigated whether elasmobranchs
      (Chiloscylliumgriseum and C. punctatum) can be conditioned in an aversive
      classical conditioning paradigm. Upon successful conditioning, the dorsal, medial
      and lateral pallium were removed (group 1) and performance tested again. In a
      second group, the same operation was performed prior to training. While
      conditioning was successful in individuals of both groups, no escape responses
      were observed. Post-operative performance was assessed and compared between
      individual and groups to reveal if the neural substrates governing avoidance
      behavior or tasks learned in a classical conditioning paradigm are located within
      the telencephalon, as has been shown for teleosts such as goldfish.

PMID- 23958860
TI  - Xenobiotic metabolizing enzyme activities in cells used for testing skin
      sensitization in vitro.
AB  - For ethical and regulatory reasons, in vitro tests for scoring potential
      toxicities of cosmetics are essential. A test strategy for investigating
      potential skin sensitization using two human keratinocytic and two human
      dendritic cell lines has been developed (Mehling et al. Arch Toxicol 86:1273
      1295, 2012). Since prohaptens may be metabolically activated in the skin,
      information on xenobiotic metabolizing enzyme (XME) activities in these cell
      lines is of high interest. In this study, XME activity assays, monitoring
      metabolite or cofactor, showed the following: all three passages of keratinocytic
      (KeratinoSens(r) and LuSens) and dendritic (U937 und THP-1) cells displayed N
      acetyltransferase 1 (NAT1) activities (about 6-60 nmol/min/mg S9-protein for
      acetylation of para-aminobenzoic acid). This is relevant since reactive species
      of many cosmetics are metabolically controlled by cutaneous NAT1. Esterase
      activities of about 1-4 nmol fluorescein diacetate/min/mg S9-protein were
      observed in all passages of investigated keratinocytic and about 1 nmol
      fluorescein diacetate/min/mg S9-protein in dendritic cell lines. This is also of
      practical relevance since many esters and amides are detoxified and others
      activated by cutaneous esterases. In both keratinocytic cell lines, activities of
      aldehyde dehydrogenase (ALDH) were observed (5-17 nmol product/min/mg cytosolic
      protein). ALDH is relevant for the detoxication of reactive aldehydes. Activities
      of several other XME were below detection, namely the investigated cytochrome
      P450-dependent alkylresorufin O-dealkylases 7-ethylresorufin O-deethylase, 7
      benzylresorufin O-debenzylase and 7-pentylresorufin O-depentylase (while NADPH
      cytochrome c reductase activities were much above the limit of quantification),
      the flavin-containing monooxygenase, the alcohol dehydrogenase as well as the UDP
      glucuronosyl transferase activities.

PMID- 23958861
TI  - FLOWERING LOCUS T/TERMINAL FLOWER1-like genes affect growth rhythm and bud set in
      Norway spruce.
AB  - The timing of bud set, as one determinant of the annual growth rhythm, is
      critical for local adaptation of the conifer Norway spruce (Picea abies).
      Previous gene expression and population genetic studies have suggested a role for
      P. abies FLOWERING LOCUS T/TERMINAL FLOWER1-Like2 (PaFTL2) in the control of
      growth cessation and bud set in Norway spruce as well as in local adaptation
      resulting in clinal variation for timing of bud set. Using transgenic plants with
      PaFTL2 driven by an inducible promoter, we found that PaFTL2 indeed induces bud
      set and most probably also growth cessation. PaFTL2 shows high expression around
      the procambium and vascular tissue and in the crown region in buds of both
      seedlings and older trees. Furthermore, PaFTL2 expression is induced in
      vegetative shoots and all bud types in late summer, when growth cessation occurs.
      This supports the notion that PaFTL2 is involved in growth cessation. A close
      paralog to PaFTL2, PaFTL1, is strongly expressed in meristems during the summer,
      possibly to repress meristem activity and the formation of needle primordia
      during this period. The temporal and spatial expression of PaFTL1 and PaFTL2
      largely complement each other, which suggests that they act in concert to control
      perennial growth in Norway spruce. 

PMID- 23958862
TI  - Regulating the redox gatekeeper: vacuolar sequestration puts glutathione
      disulfide in its place.

PMID- 23958863
TI  - The green microalga Chlamydomonas reinhardtii has a single omega-3 fatty acid
      desaturase that localizes to the chloroplast and impacts both plastidic and
      extraplastidic membrane lipids.
AB  - The omega-3 polyunsaturated fatty acids account for more than 50% of total fatty
      acids in the green microalga Chlamydomonas reinhardtii, where they are present in
      both plastidic and extraplastidic membranes. In an effort to elucidate the lipid
      desaturation pathways in this model alga, a mutant with more than 65% reduction
      in total omega-3 fatty acids was isolated by screening an insertional mutant
      library using gas chromatography-based analysis of total fatty acids of cell
      pellets. Molecular genetics analyses revealed the insertion of a TOC1 transposon
      113 bp upstream of the ATG start codon of a putative omega-3 desaturase (CrFAD7;
      locus Cre01.g038600). Nuclear genetic complementation of crfad7 using genomic DNA
      containing CrFAD7 restored the wild-type fatty acid profile. Under standard
      growth conditions, the mutant is indistinguishable from the wild type except for
      the fatty acid difference, but when exposed to short-term heat stress, its
      photosynthesis activity is more thermotolerant than the wild type. A comparative
      lipidomic analysis of the crfad7 mutant and the wild type revealed reductions in
      all omega-3 fatty acid-containing plastidic and extraplastidic glycerolipid
      molecular species. CrFAD7 was localized to the plastid by immunofluorescence in
      situ hybridization. Transformation of the crfad7 plastidial genome with a codon
      optimized CrFAD7 restored the omega-3 fatty acid content of both plastidic and
      extraplastidic lipids. These results show that CrFAD7 is the only omega-3 fatty
      acid desaturase expressed in C. reinhardtii, and we discuss possible mechanisms
      of how a plastid-located desaturase may impact the omega-3 fatty acid content of
      extraplastidic lipids. 

PMID- 23958864
TI  - LESION SIMULATING DISEASE1 interacts with catalases to regulate hypersensitive
      cell death in Arabidopsis.
AB  - LESION SIMULATING DISEASE1 (lsd1) is an important negative regulator of
      programmed cell death (PCD) in Arabidopsis (Arabidopsis thaliana). The loss-of
      function mutations in lsd1 cause runaway cell death triggered by reactive oxygen
      species. lsd1 encodes a novel zinc finger protein with unknown biochemical
      activities. Here, we report the identification of CATALASE3 (CAT3) as an lsd1
      interacting protein by affinity purification and mass spectrometry-based
      proteomic analysis. The Arabidopsis genome contains three homologous catalase
      genes (CAT1, CAT2, and CAT3). Yeast two-hybrid and coimmunoprecipitation analyses
      demonstrated that lsd1 interacted with all three catalases both in vitro and in
      vivo, and the interaction required the zinc fingers of lsd1. We found that the
      catalase enzymatic activity was reduced in the lsd1 mutant, indicating that the
      catalase enzyme activity was partially dependent on lsd1. Consistently, the lsd1
      mutant was more sensitive to the catalase inhibitor 3-amino-1,2,4-triazole than
      the wild type, suggesting that the interaction between lsd1 and catalases is
      involved in the regulation of the reactive oxygen species generated in the
      peroxisome. Genetic studies revealed that lsd1 interacted with CATALASE genes to
      regulate light-dependent runaway cell death and hypersensitive-type cell death.
      Moreover, the accumulation of salicylic acid was required for PCD regulated by
      the interaction between lsd1 and catalases. These results suggest that the lsd1
      catalase interaction plays an important role in regulating PCD in Arabidopsis. 

PMID- 23958867
TI  - Nicotine effects on attentional reorienting in mid-age adults, and interactions
      with apolipoprotein E status.
AB  - Nicotine has been shown to speed attentional reorienting in cued target detection
      tasks, and work in young adults suggest that individuals carrying the
      apolipoprotein E (APOE) e4 allele might show greater sensitivity to the cognitive
      effects of nicotine. The APOE e4 allele is associated with increased risk of
      Alzheimer's disease (AD), and increased sensitivity to nicotine might reflect
      early cholinergic differences that relate to an enhanced risk of AD. The aim of
      this study was to investigate effects of nicotine and APOE on attentional
      reorienting in mid-age participants. APOE e4 (e4+) were compared to non-APOE e4
      (e4-) carriers, and functional magnetic resonance imaging (fMRI) data acquired.
      Neural data showed that nicotine effects, and the network involved in
      reorienting, was consistent with studies in young adults. Nicotine improved
      attentional reorienting at the trend level. Although there were no behavioural
      effects of genotype, genotype effects were present neurally: e4+ showed decreased
      extrastriate activation, and enhanced effects of nicotine on reorienting in right
      middle frontal regions. Drug by genotype interactions were present in hippocampal
      and anterior cingulate regions. These results are consistent with differential
      sensitivity to nicotine according to APOE status, possibly reflecting abnormal
      cholinergic function and accelerated cognitive ageing in mid-age e4+. 

PMID- 23958868
TI  - The novice, the golf pro, and mnemonics.

PMID- 23958866
TI  - Cue reactivity in smokers: an event-related potential study.
AB  - Drugs-of-abuse may increase the salience of drug cues by sensitizing the
      dopaminergic (DA) system (Robinson and Berridge, 1993), leading to differential
      attention to smoking stimuli. Event-related potentials (ERPs) have been used to
      assess attention to smoking cues but not using an ERP component associated with
      DA-mediated salience evaluation. In this study the DA-related P2a and the P3,
      were compared in smokers (N = 21) and non-smokers (N = 21) during an attention
      selection cue exposure task including both cigarette and neutral images. We
      predicted that both the P2a and P3 would be larger to targets than non-targets,
      but larger to non-target cigarette images than non-target neutral images only in
      the smokers, reflecting smokers' evaluation of smoking stimuli as relevant even
      when they were not targets. Results indicated that smokers showed behavioral cue
      reactivity, with more false alarms to cigarette images (responding to cigarette
      images when they were not targets) than non-smokers; however, both smokers and
      non-smokers had a larger P2a and P3 to cigarette images. Thus, while smokers
      showed behavioral evidence of differential salience evaluation of the cigarette
      images, this group difference was not reflected in differential brain activity.
      These findings may reflect characteristics of the ERPs (both ERP components were
      smaller in the smokers), the smoking sample (they were not more impulsive, i.e.
      reward sensitive, than the non-smokers, in contrast to prior studies) and the
      design (all participants were aware that the aim of the study was related to
      smoking).

PMID- 23958871
TI  - 2013 "heads-up": DME MACs issue surgical dressing updates.

PMID- 23958872
TI  - Prospective study on the treatment of lower-extremity chronic venous and mixed
      ulcers using tissue-engineered skin substitute made by the self-assembly
      approach.
AB  - BACKGROUND: Despite present optimal standard treatment of lower-extremity
      ulceration, a high incidence of recurrence and treatment failure is observed. The
      objective of this project was to evaluate the effect of a self-assembled skin
      substitute (SASS) made by tissue engineering as a temporary cutaneous dressing in
      the treatment of hard-to-heal chronic ulcers. PATIENTS AND METHODS: The
      prospective uncontrolled case study includes patients suffering from venous or
      mixed ulcers lasting more than 6 months and unresponsive to compression therapy,
      with an Ankle Brachial Index greater than 0.5. Compression therapy was combined
      with the weekly application of SASS, produced from the patient's own skin cells,
      until healing. A weekly follow-up recorded wound size, skin aspect, pain,
      drainage, and percentage of wound healing. Photographs were also taken to assess
      ulcer evolution. RESULTS: Fourteen ulcers present on 5 patients were treated. A
      mean of 6.7 SASS depositions by ulcer was required for healing. Two ulcers
      developed a minor wound infection, which was treated with oral antibiotics;
      another 2 ulcers recurred, and 1 healed with a second course of treatment,
      whereas 1 ulcer had a small recurrence treated with local wound care. CONCLUSION:
      The authors' study suggests that the SASS used as a biological dressing is a
      promising treatment for hard-to-heal chronic venous and mixed ulcers that are
      unresponsive to compression therapy.

PMID- 23958873
TI  - Dakin's solution: past, present, and future.
AB  - Dakin's solution has been used for almost a century. It is a dilute solution of
      sodium hypochlorite, which is commonly known as household bleach. When properly
      applied, it can kill pathogenic microorganisms with minimum cytotoxicity. This
      article reviews its history and discusses how evolving technology might pave the
      way for a new role for this antiseptic. 

PMID- 23958874
TI  - The charcot foot: neuropathic osteoarthropathy.
AB  - Charcot joint is an uncommon but often missed complication of the neuropathic
      diabetic foot. Prompt recognition and treatment with plantar pressure
      redistribution can prevent unnecessary amputation.

PMID- 23958876
TI  - Pressure ulcer evidence-based treatment pathway integrated with evidence-based
      decisions: part 3.

PMID- 23958877
TI  - Correlation between plasma, synovial fluid and articular cartilage Interleukin-18
      with radiographic severity in 33 patients with osteoarthritis of the knee.
AB  - Osteoarthritis (OA) is a complex disease characterized by cartilage degeneration,
      secondary synovial membrane inflammation and subchondral bone changes. In recent
      years, many studies have confirmed that interleukin-18 (IL-18) is involved in the
      inflammatory process of inflammatory joint diseases. In the present study, we
      investigated IL-18 levels in plasma, synovial fluid and articular cartilage of
      patients with primary knee OA (n = 33) to analyze their relationship with
      radiographic severity. Compared to healthy controls (n = 15), OA patients had
      higher plasma and synovial fluid IL-18 concentrations(45.8 +/- 22.1 vs. 23.7 +/-
      13.6 pg/ml, P<0.001 and 75.2 +/- 40.1 vs. 28.3 +/- 11.6 pg/ml, P<0.001) as
      measured by enzyme-linked immunosorbent assay. Also,the percentage of
      immunofluorescent IL-18 positive cells in articular cartilage was significantly
      increased in OA compared to controls (46.5 +/- 10.3 vs. 2.9 +/- 1.7, P<0.001).
      Moreover, plasma, synovial fluid and articular cartilage IL-18 significantly
      positively correlated with radiographic severity, respectively (r = 0.663,
      P<0.001, r = 0.56, P = 0.001 and r = 0.884, P<0.001). Subsequent analysis
      revealed that plasma, synovial fluid and articular cartilage IL-18 levels
      positively correlated with each other (r = 0.632, P<0.001, r = 0.489, P = 0.004
      and r = 0.620, P<0.001). These data suggested that plasma, synovial fluid and
      articular cartilage IL-18 levels were significantly increased in OA patients, and
      these elevated levels were positively correlated with radiographic severity.
      Accordingly, our study supports the role of IL-18 in the pathophysiology of OA.

PMID- 23958878
TI  - Gene expression profiles of peripheral blood mononuclear cells  in primary
      biliary cirrhosis.
AB  - Previous studies on gene expression profiles in primary biliary cirrhosis (PBC)
      have exclusively focused on liver tissue or intrahepatic cells. Since the
      pathological process is systemic, other complementary studies in blood cells
      seemed to be reasonable. In this research, we try to explore differentially
      expressed genes in peripheral blood mononuclear cells (PBMCs) of PBC patients.
      Nine PBC patients and 9 healthy controls were recruited as Cohort 1 for a
      microarray study of screening. Total RNA of PBMCs from each individual was
      isolated and screened by oligonucleotide microarray (22 K). Then, differentially
      expressed genes were categorized into signaling pathways. Expression levels of
      three important genes, tyrosine kinase binding protein (TYROBP), C-C motif
      chemokine 5 (CCL5) and cathepsin L (CTSL) were confirmed by quantitative real
      time polymerase chain reaction (qRT-PCR) in a second Cohort 2 (30 PBC patients
      and 20 healthy controls). Results show that sixty-five genes differentially
      expressed in PBC were identified, 20 of which were up-regulated and 45 of which
      were down-regulated. Twenty-seven signaling pathways were identified. TYROBP and
      CCL5 were proved to be down-regulated in PBC, and CTSL was proved to be up
      regulated (p < 0.05) in PBC, which were all consistent with the screening study.
      In conclusions, the analysis of gene expression in PBMCs of PBC and the
      comparison of gene profiles between PBMCs and the liver may provide new clues to
      the pathogenesis of the disease.

PMID- 23958879
TI  - NOD2 deletion promotes cardiac hypertrophy and fibrosis induced by pressure
      overload.
AB  - Nucleotide-binding oligomerization domain-2 (NOD2, also designated CARD15), a
      member of the NOD-leucine-rich repeat (LRR) protein family (also called the
      CATERPILLAR family), is upregulated in atheroma lesions and has an important role
      in regulating the intracellular recognition of bacterial components by immune
      cells. However, the effect of NOD2 on cardiac hypertrophy induced by a
      pathological stimulus has not been determined. Here, we investigated the effects
      of NOD2 deficiency on cardiac hypertrophy induced by aortic banding (AB) in mice.
      Cardiac hypertrophy was evaluated by echocardiographic, hemodynamic,
      pathological, and molecular analyses. NOD2 expression was upregulated in
      cardiomyocytes after aortic banding surgery in wild-type (WT) mice. NOD2
      deficiency promoted cardiac hypertrophy and fibrosis 4 weeks after AB. Further,
      the enhanced activation of TLR4 and the MAPKs, NF-kappaB and TGF-beta/Smad
      pathways were found in NOD2-knockout (KO) mice compared with WT mice. Our results
      suggest that NOD2 attenuates cardiac hypertrophy and fibrosis via regulation of
      multiple pathways. 

PMID- 23958880
TI  - New chondrosarcoma cell lines and mouse models to study the link between
      chondrogenesis and chemoresistance.
AB  - Chondrosarcomas are cartilage-forming, poorly vascularized tumors. They represent
      the second malignant primary bone tumor of adults after osteosarcoma, but in
      contrast to osteosarcoma they are resistant to chemotherapy and radiotherapy,
      surgical excision remaining the only therapeutic option. Few cell lines and
      animal models are available, and the mechanisms behind their chemoresistance
      remain largely unknown. Our goal was to establish new cell lines and animal
      cancer models from human chondrosarcoma biopsies to study their chemoresistance.
      Between 2007 and 2012, 10 chondrosarcoma biopsies were collected and used for
      cell culture and transplantation into nude mice. Only one transplanted biopsy and
      one injected cell line has engrafted successfully leading to conventional central
      high-grade chondrosarcoma similar to the original biopsies. In culture, two new
      stable cell lines were obtained, one from a dedifferentiated and one from a grade
      III conventional central chondrosarcoma biopsy. Their genetic characterization
      revealed triploid karyotypes, mutations in IDH1, IDH2, and TP53, deletion in
      CDKN2A and/or MDM2 amplification. These cell lines expressed mesenchymal membrane
      markers (CD44, 73, 90, 105) and were able to produce a hyaline cartilaginous
      matrix when cultured in chondrogenic three-dimensional (3D) pellets. Using a high
      throughput quantitative RT-PCR approach, we observed that cell lines cultured in
      monolayer had lost expression of several genes implicated in cartilage
      development (COL2A1, COMP, ACAN) but restored their expression in 3D cultures.
      Chondrosarcoma cells in monolayer were sensitive to several conventional
      chemotherapeutic agents but became resistant to low doses of mafosfamide or
      doxorubicin when cultured in 3D pellets, in parallel with an altered nucleic
      accumulation of the drug. Our results indicate that the cartilaginous matrix
      produced by chondrosarcoma cells may impair diffusion of several drugs and thus
      contribute to chemoresistance. Therefore, 3D chondrogenic cell pellets constitute
      a more relevant model to study chondrosarcoma chemoresistance and may be a
      valuable alternative to animal experimentations. 

PMID- 23958883
TI  - Lung transplantation for bronchiolitis obliterans after allogeneic hematopoietic
      stem cell transplantation: unresolved questions.

PMID- 23958884
TI  - Authors' reply: lung transplantation for bronchiolitis obliterans after
      allogeneic hematopoietic stem cell transplantation: unresolved questions.

PMID- 23958885
TI  - Hepatitis C virus infection in heart transplantation: is ventricular assist
      device therapy an option?

PMID- 23958886
TI  - On the detection of anti-HLA antibodies using single antigen bead Luminex assay:
      lot-to-lot variations in MFI.

PMID- 23958887
TI  - Anti-C5 as prophylactic therapy in atypical hemolytic uremic syndrome in living
      related kidney transplantation.

PMID- 23958888
TI  - Broncho-bronchiolitis obliterans after living-donor lung transplantation: a
      unique manifestation of chronic allograft rejection.

PMID- 23958889
TI  - Rescue thrombolysis: resolution of intraglomerular thrombi after donation after
      circulatory death.

PMID- 23958890
TI  - Origin of the self-limited electron densities at Al2O3/SrTiO3 heterostructures
      grown by atomic layer deposition - oxygen diffusion model.
AB  - Recently, 2-dimensional electron gas (2-DEG) was discovered at the interface of
      Al2O3/SrTiO3 (STO) heterostructures, in which the amorphous Al2O3 layers were
      grown by atomic layer deposition (ALD). The saturated electron density at the
      Al2O3/STO heterostructures above the critical thickness of Al2O3 is explained by
      an oxygen diffusion mechanism.

PMID- 23958891
TI  - The future of Medicare supplemental insurance.

PMID- 23958892
TI  - Mesenchymal stem cell derived microvesicles: trophic shuttles for enhancement of
      sperm quality parameters.
AB  - Diminishing sperm quality during cryopreservation process ends up in a complete
      or partial loss of sperm's fertilizing potential. Rehabilitation of such affected
      sperm is crucial to improve their fertilizing potential. A variety of evidence
      has indicated that secreted microvesicles (MVs) from mesenchymal stem cells
      (MSCs) are involved in regeneration of injured endogenous cells via shuttling MSC
      trophic molecules. Sperm obtained from cauda epididymides of adult male Wistar
      rats were equally assigned to four separate groups. Following suspension in
      cryoprotectant extender, sperm were untreated or treated with increasing
      concentrations of MSC-derived MVs (25, 50 and 100MUg). After incubation in
      successive steps, sperm were cryopreserved. The frozen-thawed sperm were assessed
      for viability, motility and antioxidant capacity parameters. Consequently,
      expression levels of surface adhesion molecules (CD29, CD44, ICAM-I and VCAM-I)
      involved in sperm fusogenic and signaling properties, were assessed by flow
      cytometry. Results showed an enhanced quality parameters and adhesive properties
      of cryopreserved sperm following treatment with MSC-derived MVs. 

PMID- 23958893
TI  - Effect of peptide conformation on TiO2 biomineralization.
AB  - The conformational effects of lysine-rich peptides on the biomineralization of
      TiO2 were investigated. The biomineralization activity of the peptide was
      dependent on the spatial proximity of the amino groups, which is determined by
      the secondary structure. 

PMID- 23958894
TI  - Allosteric inhibitors of HMG-CoA reductase, the key enzyme involved in
      cholesterol biosynthesis.
AB  - The corrole-based catalytic antioxidant reduced the cholesterol biosynthesis
      ability of macrophages, harvested from mice treated with it. and a non-redox
      active analogue of it affect the committed step of the biosynthetic pathway--the
      HMG-CoA reductase catalysed reaction--by acting as allosteric inhibitors of this
      key enzyme.

PMID- 23958895
TI  - Obese men have more advanced and more aggressive prostate cancer at time of
      surgery than non-obese men after adjusting for screening PSA level and age:
      results from two independent nested case-control studies.
AB  - BACKGROUND: It remains unclear whether the hemodilution effect of body mass index
      (BMI) on PSA levels translates to inappropriate prostate cancer (PCa) screening
      in obese men. To address this, we conducted two nested case-control studies
      within prospective cohorts of men undergoing radical prostatectomy for newly
      diagnosed PCa. METHODS: We identified 1817 men with BMI ?30 kg m(-2) (cases) and
      1244 men with BMI <25 kg m(-2) (controls) who underwent surgery to treat PCa at
      Mayo Clinic in Rochester between 2000 and 2009. Cases and controls were frequency
      matched on age and PSA level. In a similar manner, we identified 206 cases and
      133 controls treated at Mayo Clinic in Florida between 2006 and 2011. We employed
      logistic regression models to evaluate the association of pathologic features of
      aggressiveness with obesity status. RESULTS: After adjusting for age and PSA
      level, we noted that obese men in the Rochester population are more likely to
      present with Gleason grade 8-10 tumors (OR= 1.50; 95% CI 1.14-1.96; P=0.003) and
      pT3, pT4, pTxN+ stage disease (OR=1.30; 95% CI 1.05-1.62). We noted a similar
      association seminal vesicle involvement (OR= 1.41; 95% CI 1.03-1.92; P=0.03).
      Results from the smaller Florida population supported these same associations but
      did not achieve conventional statistical significance. CONCLUSIONS: Obese men
      present with more aggressive PCa tumors compared with non-obese men of similar
      age and PSA screening values. If confirmed, this would support the need to
      explore PSA-based screening in obese men to possibly account for a hemodilution
      effect.

PMID- 23958897
TI  - Saethre-Chotzen syndrome with an atypical phenotype: identification of TWIST
      microdeletion by array CGH.
AB  - Saethre-Chotzen syndrome is a very rare autosomal dominant congenital disorder
      characterized by craniosynostosis and acrocephalosyndactyly. It is caused by a
      mutation in TWIST1, located on chromosome 7p21. A shortage of functional TWIST1
      protein affects the development and maturation of cells in the skull, face, and
      limbs. The patient described in this report displayed craniofacial features
      classic for Saethre-Chotzen syndrome, including craniosynostosis, low-set ears,
      small pinna with prominent crura, a high-arched palate, and a simian crease on
      the left hand. He did not have the limb anomalies commonly seen in patients with
      Saethre-Chotzen syndrome, and the results of conventional chromosome analysis
      were normal. However, results of a microarray-based comparative genomic
      hybridization (array CGH) study confirmed the karyotype
      of46,XY.7p21.1p15.3(15,957,375-20,331,837)x1, a region that includes TWIST1.
      Subsequent fluorescent in situ hybridization analysis confirmed this result. No
      other chromosome was involved in the rearrangement. This case illustrates the
      important contribution of array CGH to the identification of TWIST
      microdeletions, even in a patient not showing the phenotype typical of Saethre
      Chotzen syndrome.

PMID- 23958896
TI  - Pharmacodynamic study of disulfiram in men with non-metastatic recurrent prostate
      cancer.
AB  - BACKGROUND: Preclinical drug screens identified disulfiram as a potent in vitro
      inhibitor of prostate cancer (PCa) cell growth. Although many mechanisms for its
      anticancer activity have been proposed, tumor suppressor gene re-expression
      through promoter demethylation emerged as one of the more plausible. METHODS: We
      conducted an open-label, dose escalation trial of disulfiram in men with non
      metastatic recurrent PCa after local therapy. Dose escalation occurred if a
      demethylating 'response' (that is, ?10% decrease in peripheral blood mononuclear
      cell (PBMC) global 5-methyl cytosine (5(me)C) content) was observed in <3
      patients in cohort 1. Cohorts 1 and 2 received disulfiram 250 mg and 500 mg
      daily, respectively. The primary end point was the proportion of subjects with a
      demethylation response. Secondary end points included the rate of PSA progression
      at 6 months, changes in PSA doubling time and safety/tolerability. RESULTS:
      Changes in global 5(me)C content were observed in two of nine patients (22.2%) in
      cohort 1 and 3 of 10 (30.0%) in cohort 2. Only five subjects were on trial for ?6
      months, all were in cohort 1 and all had PSA progression by 6 months. No changes
      in PSA kinetics were observed in either cohort. Disulfiram was poorly tolerated
      with six patients experiencing grade 3 adverse events (three per cohort). Three
      of the responders displayed pretreatment instability in their 5(me)C content.
      CONCLUSIONS: A minority of patients had transient global PBMC demethylation
      changes. Instability in 5(me)C may limit the reproducibility of these findings,
      limiting our ability to confirm our hypothesis. Given the toxicities and no
      clinical benefits, further development of disulfiram should not be pursued in
      this population.

PMID- 23958899
TI  - Primary central neurocytoma of the mesencephalic tectum in a pediatric patient.
AB  - PURPOSE: Neurocytomas are tumors or neuronal differentiation, typically located
      within the supratentorial ventricular system. The extraventricular location is
      uncommon. A limited number of cases involving the brainstem have been reported
      and may be misdiagnosed as brainstem gliomas. Furthermore, midbrain neurocytomas
      are extremely rare, and no similar cases in pediatric patients have been reported
      in the literature to date. Brainstem location of neurocytomas often precludes
      gross total removal of the lesion, and in these cases, adjuvant therapies may be
      helpful. METHODS: We report a case of a 16-year-old child who presented with
      signs and symptoms of increased intracranial pressure. The magnetic resonance
      imaging study demonstrated the presence of a primary mesencephalic tectum lesion
      causing obstructive hydrocephalus. The patient underwent emergent
      ventriculoperitoneal shunt implantation, resolving the hydrocephalus and the
      clinical symptoms. The lesion was partially removed through a suboccipital
      craniotomy and supracerebellar infratentorial approach to the mesencephalic
      tectum, without intraoperative complications. RESULTS: Histological examination
      of the lesion was consistent with the diagnosis of extraventricular neurocytoma.
      The patient was referred to the oncology department for additional treatment with
      Gamma Knife radiosurgery. CONCLUSIONS: Although brainstem neurocytoma is rare,
      this case demonstrates that it should be included in the differential diagnosis
      of brainstem gliomas. Because of brainstem tumor location, complete surgical
      removal may be challenging or not possible, with a high risk of postoperative
      neurological deficits. Adjuvant therapies may prevent local tumor growth in cases
      of tumor remnants or recurrences following microsurgery in selected cases.

PMID- 23958900
TI  - Application of indocyanine green (ICG) fluorescence  for endoscopic biopsy of
      intraventricular tumors.
AB  - BACKGROUND: Many reports have already indicated the benefit of pathological
      diagnosis of intra- and periventricular tumors with neuroendoscopic biopsy.
      However, it is also well known that studies can be occasionally inconclusive
      because of the small and/or inadequate samples for identification of abnormal
      tissues. The application of indocyanine green (ICG) fluorescence for endoscopical
      tumor biopsy under the intraventricular surroundings is a new area not previously
      reported. We attempted visual differentiation of intraventricular lesions from
      the surrounding structure using ICG fluorescence and considered the most
      appropriate region for biopsy. METHODS: Three cases (13-14 year-old boys) with
      secondary hydrocephalus caused by intra- and periventricular tumors were operated
      for endoscopic transventricular biopsy combined with endoscopic third
      ventriculostomy. Final pathological diagnoses were suprasellar malignant lymphoma
      and germ cell tumors in two patients, both associated with intraventricular
      dissemination. Enhanced tumor visualization with 12.5 mg of ICG administration
      was obtained using the D-light P light equipment and ICG telescope 5.8 mm/19 cm.
      RESULTS: It was possible to identify the tumor mass margins themselves and detect
      the differences of intratumoral ICG accumulation. The areas of tumor
      dissemination were identifiable by neuroendoscopy but unable to be visualized by
      ICG fluorescence. CONCLUSIONS: We were able to obtain an ICG fluorescence imaging
      inside the cerebral ventricles by new D-light P system comprised of a camera head
      telescope. ICG fluorescence with neuroendoscopy can provide useful information
      for choosing the point of biopsy of intra- and periventricular tumors. However,
      we need to assess if the ICG accumulation site is the most appropriate for
      biopsy.

PMID- 23958901
TI  - The fate of Au25(SR)18 clusters upon ligand exchange with binaphthyl-dithiol:
      interstaple binding vs. decomposition.
AB  - The ligand exchange reaction between monodisperse Au25(2-PET)18 (2-PET: 2
      phenylethylthiolate) clusters and 1,1'-binaphthyl-2,2'-dithiol (BINAS) was long
      thought to induce decomposition of the cluster (Si et al., J. Phys. Chem. C,
      2009). We repeated the experiment and analyzed the reaction products using MALDI
      TOF mass spectrometry. The spectra clearly indicate successful ligand exchange,
      bidentate binding of the BINAS ligand and intact Au25 clusters. The reaction
      products are identified as Au25(2-PET)18-2x(BINAS)x (x = 1-4) for a 24 h reaction
      with a 50-fold molar excess of BINAS. Two likely binding motifs are discussed.
      Analysis of atomic distances in both the cluster and the free ligand indicates
      interstaple binding connecting the central sulfur atom of the protecting
      (SRAu)2SR with the outer sulfur atom of a second unit. The results presented have
      implications on the binding position of BINAS in Au38(SR)24-2x(BINAS)x clusters. 

PMID- 23958902
TI  - Non-vascular drug eluting stents as localized controlled drug delivery platform:
      preclinical and clinical experience.
AB  - Stents occupy an important place in the medical field for their widespread
      application. They have been used in vascular as well as in non-vascular organs
      for various reasons. Among vascular stents, development of coronary drug eluting
      stents (DESs) has completely revolutionised the percutaneous coronary
      intervention. Similarly, attempts have been made to make use of this modality in
      non-vascular organs. This paper focuses on the preclinical and clinical
      experience with drug-eluting non-vascular stents with emphasis on drug delivery
      systems and regulatory requirements for their development. 

PMID- 23958903
TI  - Redox nanoparticle therapeutics to cancer--increase in therapeutic effect of
      doxorubicin, suppressing its adverse effect.
AB  - The ultimate goal of cancer chemotherapy is to achieve a cure without causing any
      adverse effects. We have developed a pH-sensitive redox nanoparticle (RNP(N)),
      which disintegrates under acidic conditions and exposes nitroxide radicals,
      leading to strongly scavenging reactive oxygen species (ROS). After intravenous
      administration of RNP(N) to tumor bearing mice, it effectively accumulated in
      tumors due to the leaky neovascular and immature lymphatic system and scavenged
      ROS, resulting in suppression of inflammation and activation of NF-kB, after
      disintegration of RNP(N) in the tumors. Pre-administration of RNP(N) prior to
      treatments with anticancer agents, doxorubicin, to tumor-bearing mice
      significantly suppressed the progression of tumor size, compared to low-molecular
      weight 4-hydroxy-TEMPO. Interestingly, the administration of RNP(N) suppressed
      adverse effects of doxorubicin to normal organs due to the scavenging ROS and
      suppression of inflammation, which was confirmed by reduction in lactate
      dehydrogenase and creatine phosphokinase activities in plasma. RNP(N) is thus
      anticipated as a novel and ideal adjuvant for cancer chemotherapy. 

PMID- 23958904
TI  - The micronutrient zinc inhibits EAEC strain 042 adherence, biofilm formation,
      virulence gene expression, and epithelial cytokine responses benefiting the
      infected host.
AB  - Enteroaggregative Escherichia coli (EAEC) is a major pathogen worldwide,
      associated with diarrheal disease in both children and adults, suggesting the
      need for new preventive and therapeutic treatments. We investigated the role of
      the micronutrient zinc in the pathogenesis of an E. coli strain associated with
      human disease. A variety of bacterial characteristics-growth in vitro, biofilm
      formation, adherence to IEC-6 epithelial cells, gene expression of putative EAEC
      virulence factors as well as EAEC-induced cytokine expression by HCT-8 cells-were
      quantified. At concentrations (<= 0.05 mM) that did not alter EAEC growth (strain
      042) but that are physiologic in serum, zinc markedly decreased the organism's
      ability to form biofilm (P<0.001), adhere to IEC-6 epithelial cells (P<0.01), and
      express putative EAEC virulence factors (aggR, aap, aatA, virK) (P<0.03). After
      exposure of the organism to zinc, the effect on virulence factor generation was
      prolonged (> 3 h). Further, EAEC-induced IL-8 mRNA and protein secretion by HCT-8
      epithelial cells were significantly reduced by 0.05 mM zinc (P<0.03). Using an in
      vivo murine model of diet-induced zinc-deficiency, oral zinc supplementation (0.4
      ug/mouse daily) administered after EAEC challenge (10 (10) CFU/mouse)
      significantly abrogated growth shortfalls (by>90%; P<0.01); furthermore, stool
      shedding was reduced (days 9-11) but tissue burden of organisms in the intestine
      was unchanged. These findings suggest several potential mechanisms whereby
      physiological levels of zinc alter pathogenetic events in the bacterium (reducing
      biofilm formation, adherence to epithelium, virulence factor expression) as well
      as the bacterium's effect on the epithelium (cytokine response to exposure to
      EAEC) to alter EAEC pathogenesis in vitro and in vivo. These effects may help
      explain and extend the benefits of zinc in childhood diarrhea and malnutrition. 

PMID- 23958905
TI  - The attenuated nine mile phase II clone 4/RSA439 strain of Coxiella burnetii is
      highly virulent for severe combined immunodeficient (SCID) mice.
AB  - The Nine Mile phase II clone 4 (NMIIC4) strain of Coxiella burnetii is an
      attenuated phase II strain that has lost the genes for virulence determinant type
      1 lipopolysaccharide. These bacteria were very virulent for severe combined
      immunodeficient (SCID) mice. The lethal dose 50 (LD50) was ~10 bacteria. Infected
      SCID mice died between Day 28 and Day 53 post-infection. At termination of the
      experiment (Day 60) only 5 of 24 mice had survived. The degree of splenomegaly
      was directly related to the bacterial load in the SCID mice spleens. The NMIIC4
      was avirulent in immunocompetent wild mice and bacterial DNA copies in splenic
      tissue were extremely low. The SCID mice that were inoculated with high doses of
      heat inactivated NMIIC4 C. burnetii were all alive at Day 60 and without
      splenomegaly. It appears that the phase I lipopolysaccharide present in virulent
      Nine Mile phase I but not in attenuated NMIIC4 is not the only virulence factor
      for C. burnetii.

PMID- 23958906
TI  - The complex relationship between weather and dengue virus transmission in
      Thailand.
AB  - Using a novel analytical approach, weather dynamics and seasonal dengue virus
      transmission cycles were profiled for each Thailand province, 1983-2001, using
      monthly assessments of cases, temperature, humidity, and rainfall. We observed
      systematic differences in the structure of seasonal transmission cycles of
      different magnitude, the role of weather in regulating seasonal cycles, necessary
      versus optimal transmission "weather-space," basis of large epidemics, and
      predictive indicators that estimate risk. Larger epidemics begin earlier, develop
      faster, and are predicted at Onset change-point when case counts are low.
      Temperature defines a viable range for transmission; humidity amplifies the
      potential within that range. This duality is central to transmission. Eighty
      percent of 1.2 million severe dengue cases occurred when mean temperature was 27
      29.5 degrees C and mean humidity was > 75%. Interventions are most effective when
      applied early. Most cases occur near Peak, yet small reductions at Onset can
      substantially reduce epidemic magnitude. Monitoring the Quiet-Phase is
      fundamental in effectively targeting interventions pre-emptively.

PMID- 23958907
TI  - Gongylonema pulchrum infection in a resident of Williamsburg, Virginia, verified
      by genetic analysis.
AB  - We describe the thirteenth reported case of human infection with Gongylonema spp.
      in the United States and the first to be confirmed as Gongylonema pulchrum. The
      parasite described was isolated from the oral cavity of a resident of
      Williamsburg, Virginia. The identity of the parasite was verified through
      morphological and genetic approaches, and provided the first genetic confirmation
      of a Gongylonema sp. in humans.

PMID- 23958908
TI  - Characterization of three novel adhesins of Leptospira interrogans.
AB  - We report cloning, expression, purification, and characterization of three
      predicted leptospiral membrane proteins (LIC11360, LIC11009, and LIC11975). In
      silico analysis and proteinase K accessibility data suggest that these proteins
      might be surface exposed. We show that proteins encoded by LIC11360, LIC11009 and
      LIC11975 genes interact with laminin in a dose-dependent and saturable manner.
      The proteins are referred to as leptospiral surface adhesions 23, 26, and 36
      (Lsa23, Lsa26, and Lsa36), respectively. These proteins also bind plasminogen and
      generate active plasmin. Attachment of Lsa23 and Lsa36 to fibronectin occurs
      through the involvement of the 30-kDa and 70-kDa heparin-binding domains of the
      ligand. Dose-dependent, specific-binding of Lsa23 to the complement regulator
      C4BP and to a lesser extent, to factor H, suggests that this protein may
      interfere with the complement cascade pathways. Leptospira spp. may use these
      interactions as possible mechanisms during the establishment of infection.

PMID- 23958909
TI  - Population genetic and admixture analyses of Culex pipiens complex (Diptera:
      Culicidae) populations in California, United States.
AB  - Microsatellite markers were used to genetically characterize 19 Culex pipiens
      complex populations from California. Two populations showed characteristics of
      earlier genetic bottlenecks. The overall FST value and a neighbor-joining tree
      suggested moderate amounts of genetic differentiation. Analyses using Structure
      indicated K = 4 genetic clusters: Cx. pipiens form pipiens L., Cx.
      quinquefasciatus Say, Cx. pipiens form molestus Forskal, and a group of
      genetically similar individuals of hybrid origin. A Discriminant Analysis of
      Principal Components indicated that the latter group is a mixture of the other
      three taxa, with form pipiens and form molestus contributing somewhat more
      ancestry than Cx. quinquefasciatus. Characterization of 56 morphologically
      autogenous individuals classified most as Cx. pipiens form molestus, and none as
      Cx. pipiens form pipiens or Cx. quinquefasciatus. Comparison of California
      microsatellite data with those of Cx. pipiens pallens Coquillett from Japan
      indicated the latter does not contribute significantly to genotypes in
      California.

PMID- 23958910
TI  - Progress toward elimination of hepatitis B virus transmission in Oman: impact of
      hepatitis B vaccination.
AB  - Approximately 2-7% of the Omani population has chronic hepatitis B virus (HBV)
      infection. To decrease this burden, universal childhood hepatitis B vaccination
      was introduced in Oman in 1990. The hepatitis B vaccination strategy and reported
      coverage were reviewed. To assess the impact of the program on chronic HBV
      seroprevalence, a nationally representative seroprevalence study was conducted in
      Oman in 2005. Since 1991, hepatitis B vaccination in Oman has reached almost
      every eligible child, with reported coverage of >= 97% for the birth dose and >=
      94% for three doses. Of 175 children born pre-vaccine introduction, 16 (9.1%) had
      evidence of HBV exposure, and 4 (2.3%) had evidence of chronic infection. Of
      1,890 children born after vaccine introduction, 43 (2.3%) had evidence of HBV
      exposure, and 10 (0.5%) had evidence of chronic infection. Oman has a strong
      infant hepatitis B vaccination program, resulting in a dramatic decrease in
      chronic HBV seroprevalence.

PMID- 23958911
TI  - Anatomy of the spermatophore in triatomines (Hemiptera, Reduviidae, Triatominae)
      and its applications to the study of Chagas disease vector biology.
AB  - The present study focused on spermatophore structure, transfer, and subsequent
      destination inside bloodfeeding females of the species Triatoma infestans and
      Rhodnius neglectus. The morphology of the spermatophore differed between the
      species studied, such that in T. infestans, the shape was ovaloid, whereas in R.
      neglectus, the shape resembled a rod. Structures' spine-like cuticulars
      distributed across the inner surface of the vagina of both species were observed;
      however, the role of these cuticulars is unknown in Triatominae. In both species,
      there was an opening in the spermatophore exactly where the common oviduct is
      connected, thereby making it possible to confirm that the process of spermatozoid
      migration takes place through this opening. The results obtained show that the
      spermatophores of T. infestans and R. neglectus differ in size, shape, and
      structure. Therefore, they can be used as taxonomic markers and may provide
      information regarding physiology and evolution.

PMID- 23958912
TI  - Optimization, validation, and application of a real-time PCR protocol for
      quantification of viable bacterial cells in municipal sewage sludge and biosolids
      using reporter genes and Escherichia coli.
AB  - Biosolids result from treatment of sewage sludge to meet jurisdictional
      standards, including pathogen reduction. Once government regulations are met,
      materials can be applied to agricultural lands. Culture-based methods are used to
      enumerate pathogen indicator microorganisms but may underestimate cell densities,
      which is partly due to bacteria existing in a viable but non-culturable
      physiological state. Viable indicators can also be quantified by realtime
      polymerase chain reaction (qPCR) used with propidium monoazide (PMA), a dye that
      inhibits amplification of DNA found extracellularly or in dead cells. The
      objectives of this study were to test an optimized PMA-qPCR method for viable
      pathogen detection in wastewater solids and to validate it by comparing results
      to data obtained by conventional plating. Reporter genes from genetically marked
      Pseudomonas sp. UG14Lr and Agrobacterium tumefaciens 542 cells were spiked into
      samples of primary sludge, and anaerobically digested and Lystek-treated
      biosolids as cell-free DNA, dead cells, viable cells, and mixtures of live and
      dead cells, followed by DNA extraction with and without PMA, and qPCR. The
      protocol was then used for Escherichia coli quantification in the three matrices,
      and results compared to plate counts. PMA-qPCR selectively detected viable cells,
      while inhibiting signals from cell-free DNA and DNA found in membrane-compromised
      cells. PMA-qPCR detected 0.5-1 log unit more viable E. coli cells in both primary
      solids and dewatered biosolids than plate counts. No viable E. coli was found in
      Lystek-treated biosolids. These data suggest PMA-qPCR may more accurately
      estimate pathogen cell numbers than traditional culture methods.

PMID- 23958913
TI  - Isolation of an endophytic fungus producing baccatin III from Taxus wallichiana
      var. mairei.
AB  - The objective of this study was to isolate endophytic fungi producing baccatin
      III from yew for the purpose of baccatin III and paclitaxel manufacture. Surface
      sterilized bark of Taxus wallichiana var. mairei was used as source material with
      potato dextrose agar culture medium for isolation of endophytic fungi. Fungal
      cultures were extracted with a mixture of chloroform/methanol (1:1, v/v) and the
      baccatin III in the extracts was determined and authenticated with LC-MS. An
      endophytic fungus that produced baccatin III was identified by ITS rDNA and 26S
      D1/D2 rDNA sequencing. A total of 192 endophytic fungal strains were isolated
      from T. wallichiana var. mairei. Only one of the 192 strains produced baccatin
      III and it was identified as Diaporthe phaseolorum. The productivity of this
      strain cultured in PDA culture medium was 0.219 mg/l. The isolated endophytic
      fungus produced baccatin III at a relatively high level and shows promise as a
      producing strain for baccatin III and paclitaxel manufacture after strain
      improvement.

PMID- 23958915
TI  - Dealing with a broken bottle of desflurane.

PMID- 23958914
TI  - Pharmacological and nonpharmacological prevention   of fentanyl-induced cough: a
      meta-analysis.
AB  - Fentanyl-induced cough (FIC) is often observed after intravenous bolus
      administration of fentanyl during anesthesia induction. This meta-analysis
      assessed the efficacy of pharmacological and nonpharmacological interventions to
      reduce the incidence of FIC. We searched for randomized controlled trials
      comparing pharmacological or nonpharmacological interventions with controls to
      prevent FIC; we included 28 studies retrieved from Pub-Med, Embase, and Cochrane
      Library. Overall incidence of FIC was approximately 31 %. Lidocaine [odds ratio
      (OR) = 0.29, 95 % confidence interval (CI) 0.21-0.39], N-methyl-D-aspartate
      (NMDA) receptor antagonists (OR 0.09, 95 % CI 0.02-0.42), propofol (OR 0.07, 95 %
      CI 0.01-0.36), a2 agonists (OR 0.32, 95 % CI 0.21-0.48), b2 agonists (OR 0.10, 95
      % CI 0.03-0.30), fentanyl priming (OR 0.33, 95 % CI 0.19-0.56), and slow
      injection of fentanyl (OR 0.25, 95 % CI 0.11-0.58)] were effective in decreasing
      the incidence of FIC, whereas atropine (OR 1.10, 95 % CI 0.58-2.11) and
      benzodiazepines (OR 2.04, 95 % CI 1.33-3.13) were not effective. This meta
      analysis found that lidocaine, NMDA receptor antagonists, propofol, a2 agonists,
      b2 agonists, and priming dose of fentanyl were effective in preventing FIC, but
      atropine and benzodiazepines were not. Slow injection of fentanyl was effective
      in preventing FIC, but results depend on the speed of administration.

PMID- 23958916
TI  - Comparison of arterial lactate levels during sevoflurane   versus spinal
      anesthesia in elderly females undergoing total knee   arthroplasty.

PMID- 23958918
TI  - Monitoring of residual disease by next-generation deep-sequencing of RUNX1
      mutations can identify acute myeloid leukemia patients with resistant disease.
AB  - We studied the utility and clinical relevance of RUNX1 (runt-related
      transcription factor 1) mutations and their application as residual disease
      detection markers using next-generation deep-sequencing. Mutation screening was
      prospectively performed in 814 acute myeloid leukemia patients. At diagnosis,
      211/814 (25.9%) patients harbored mutations with a median clone size of 39%
      (range: 2-96%). Furthermore, in 57 patients paired samples from diagnosis and
      relapse were analyzed. In 47/57 (82.5%) cases the same alterations detected at
      diagnosis were present at relapse, whereas in 1/57 (1.8%) cases the mutation from
      the diagnostic sample was no longer detectable. Discrepancies were observed in
      9/57 (15.8%) cases, also including the occurrence of novel RUNX1 mutations not
      restricted to those regions affected at diagnosis. Moreover, in 103 patients the
      prognostic impact of residual levels of RUNX1 mutations during complete remission
      was studied. Separation of patients according to median residual mutation burden
      into 'good responders' and 'poor responders' (median: 3.61%; range: 0.03-48.0%)
      resulted in significant differences of both event-free (median 21.0 vs. 5.7
      months, P<0.001) and overall survival (OS; median 56.9 vs. 32.0 months, P=0.002).
      In conclusion, deep-sequencing revealed that RUNX1 mutations qualify as patient
      specific markers for individualized disease monitoring. The measurement of
      mutation load may refine the assignment into distinct risk categories and
      treatment strategies.

PMID- 23958919
TI  - Antibody-dependent cellular cytotoxicity of the optimized anti-CD20 monoclonal
      antibody ublituximab on chronic lymphocytic leukemia cells with the 17p deletion.

PMID- 23958917
TI  - Origins of aberrant DNA methylation in acute myeloid leukemia.
AB  - Aberrant DNA methylation patterns are a characteristic feature of cancer
      including myeloid malignancies such as acute myeloid leukemia (AML). The
      mechanisms behind aberrant DNA methylation have long remained obscure. New genome
      wide studies have elucidated the genome and epigenome of solid tumors and AML.
      Molecular subtypes of AML were found to exhibit highly distinct DNA methylation
      profiles. Clonal evolution patterns of AML were recently dissected and might
      shape epigenetic dysregulation. Also, recurrent mutations in epigenetic modifying
      enzymes were identified in AML and linked to distinct DNA methylation signatures.
      The genetic background, thus, takes center stage as a driver of epigenetic
      dysregulation in AML. First mechanistic insights into the dysregulation of DNA
      methylation by recurrent mutations have already been gained. Other studies
      suggest that epigenomic plasticity and aging-associated changes in DNA
      methylation also contribute extensively to aberrant DNA methylation in cancer.
      Epigenetic dysregulation, therefore, seems to also occur independently of the
      genetic background. Furthermore, global changes in chromatin conformation and
      nuclear organization have also been proposed as potential contributors to
      aberrant DNA methylation. This review will summarize and discuss current concepts
      regarding the mechanisms behind aberrant DNA methylation in cancer and
      specifically AML. 

PMID- 23958921
TI  - Prognostic significance of whole-body MRI in patients with monoclonal gammopathy
      of undetermined significance.
AB  - Radiological skeletal survey or computed tomography are currently applied to
      assess bone diseases in patients with monoclonal plasma cell disorders. Whole
      body magnetic resonance imaging (whole-body MRI) allows detecting the
      infiltration of clonal cells in nearly the whole bone marrow compartment even
      before bone destruction has occurred. Those MRI results (i.e., patterns of bone
      marrow infiltration) have been demonstrated to be of prognostic significance in
      patients with symptomatic as well as asymptomatic multiple myeloma. We have
      therefore analyzed the findings of whole-body MRI in 137 consecutive individuals
      with monoclonal gammopathy of undetermined significance (MGUS). A focal
      infiltration pattern was detected in 23.4% of patients. Presence and number of
      focal lesions as well as value of M-Protein were of independent prognostic
      significance for progression into a symptomatic disease requiring systemic
      treatment (P=0.02; P<0.0001 and P=0.0005, respectively). Lower homogeneous signal
      intensities in T1-weighted images were related to a physiologically higher bone
      marrow cellularity in younger individuals (P=0.002). We conclude that whole-body
      MRI identifies patients with focal accumulations of presumably monoclonal cells
      in bone marrow with prognostic impact concerning the risk of progression into
      symptomatic disease. 

PMID- 23958920
TI  - Chemical genomic screening identifies LY294002 as a modulator of glucocorticoid
      resistance in MLL-rearranged infant ALL.
AB  - Successful treatment results for MLL-rearranged Acute Lymphoblastic Leukemia
      (ALL) in infants remain difficult to achieve. Significantly contributing to
      therapy failure is poor response to glucocorticoids (GCs), like prednisone. Thus,
      overcoming resistance to these drugs may be a crucial step towards improving
      prognosis. We defined a gene signature that accurately discriminates between
      prednisolone-resistant and prednisolone-sensitive MLL-rearranged infant ALL
      patient samples. In the current study, we applied Connectivity Map analysis to
      perform an in silico screening for agents capable of reversing the prednisolone
      resistance profile and induce sensitivity. These analyses revealed that LY294002,
      a PI3K inhibitor, would potentially fulfill this task. Subsequent validation
      experiments demonstrated that indeed LY294002, and other known PI3K inhibitors,
      markedly sensitized otherwise resistant MLL-rearranged ALL cells to prednisolone
      in vitro. Using quantitative RT-PCR analyses, we validated the modulating effects
      of the PI3K inhibitors on the expression of the genes present in our prednisolone
      resistance profile. Interestingly, prednisolone-sensitizing actions may be
      mediated by inhibition of FCGR1B. Moreover, only high-level expression of FCGR1B
      showed to be predictive for a poor prognosis and shRNA-mediated knock-down of
      FCGR1B led to in vitro prednisolone sensitization. Thus, implementing FDA
      approved PI3K inhibitors in current treatments may potentially improve the GC
      response and prognosis in patients with MLL-rearranged ALL. 

PMID- 23958922
TI  - Lenalidomide and low-dose dexamethasone for newly diagnosed primary plasma cell
      leukemia.

PMID- 23958923
TI  - Costimulation improves the killing capability of T cells redirected to tumor
      cells expressing low levels of CD33: description of a novel modular targeting
      system.
AB  - Owing to their clinical success, there is growing interest in novel bispecific
      antibodies (bsAbs) for retargeting of T cells to tumor cells including for the
      treatment of acute myeloid leukemia (AML). One potential target for retargeting
      of T cells to AML blasts is the surface molecule CD33. Here we describe a novel
      modular targeting platform that consists of a universal effector module (EM) and
      individual target modules (TMs). Both modules can form an immune complex via a
      peptide epitope. The resulting targeting complex can functionally replace a
      conventional bsAb. By fusion of a costimulatory domain (for example, the
      extracellular CD137 ligand domain) to the TM, the targeting complex can even
      provide a costimulatory signal to the redirected T cells at their side of
      interaction with the tumor cell. Furthermore, we observed that an efficient
      killing of tumor cells expressing low levels of the tumor target CD33 becomes
      critical at low effector-to-target cell ratios but can be improved by
      costimulation via CD137 using our novel targeting system. 

PMID- 23958924
TI  - Activation of the lectin pathway of complement in pig-to-human
      xenotransplantation models.
AB  - BACKGROUND: Natural IgM containing anti-Gal antibodies initiates classic pathway
      complement activation in xenotransplantation. However, in ischemia-reperfusion
      injury, IgM also induces lectin pathway activation. The present study was
      therefore focused on lectin pathway as well as interaction of IgM and mannose
      binding lectin (MBL) in pig-to-human xenotransplantation models. METHODS:
      Activation of the different complement pathways was assessed by cell enzyme
      linked immunosorbent assay using human serum on wild-type (WT) and alpha
      galactosyl transferase knockout (GalTKO)/hCD46-transgenic porcine aortic
      endothelial cells (PAEC). Colocalization of MBL/MASP2 with IgM, C3b/c, C4b/c, and
      C6 was investigated by immunofluorescence in vitro on PAEC and ex vivo in pig leg
      xenoperfusion with human blood. Influence of IgM on MBL binding to PAEC was
      tested using IgM depleted/repleted and anti-Gal immunoabsorbed serum. RESULTS:
      Activation of all the three complement pathways was observed in vitro as
      indicated by IgM, C1q, MBL, and factor Bb deposition on WT PAEC. MBL deposition
      colocalized with MASP2 (Manders' coefficient [3D] r=0.93), C3b/c (r=0.84), C4b/c
      (r=0.86), and C6 (r=0.80). IgM colocalized with MBL (r=0.87) and MASP2 (r=0.83).
      Human IgM led to dose-dependently increased deposition of MBL, C3b/c, and C6 on
      WT PAEC. Colocalization of MBL with IgM (Pearson's coefficient [2D] rp=0.88),
      C3b/c (rp=0.82), C4b/c (rp=0.63), and C6 (rp=0.81) was also seen in ex vivo
      xenoperfusion. Significantly reduced MBL deposition and complement activation was
      observed on GalTKO/hCD46-PAEC. CONCLUSION: Colocalization of MBL/MASP2 with IgM
      and complement suggests that the lectin pathway is activated by human anti-Gal
      IgM and may play a pathophysiologic role in pig-to-human xenotransplantation.

PMID- 23958925
TI  - Effect of a novel nuclear factor-kappaB activation inhibitor on renal ischemia
      reperfusion injury.
AB  - BACKGROUND: In kidney transplantation, the relationship between prolonged warm or
      cold ischemic storage of kidneys and a higher incidence of delayed graft function
      is previously known, and delayed graft function has been known to aggravate poor
      long-term graft survival. We investigated the effect of a novel nuclear factor
      kappaB activation inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on renal
      ischemia-reperfusion (I/R) injury. METHODS: DHMEQ was administered to Lewis rats
      once just before renal artery clamping (DHMEQ pretreatment group), and the effect
      on I/R injury was investigated. RESULTS: In the DHMEQ pretreatment group, the 24
      hr urine volume on days 1 to 3 after I/R was significantly larger, and the
      protein concentration of the urine on days 2 to 7 was significantly smaller than
      in the untreated group. The serum creatinine level was significantly improved,
      and significantly lower levels of the inflammatory cells and inflammatory
      cytokines were present in the kidneys on day 1. The relative ratio of nuclear to
      cytoplasmic nuclear factor-kappaB and oxidative stress of kidney tissue on day 1
      were significantly decreased. CONCLUSIONS: Treatment with DHMEQ before renal
      artery clamping may therefore be useful for renal I/R injury and application to
      renal transplantation is expected.

PMID- 23958926
TI  - No acceleration of UV-induced skin carcinogenesis from evenly spread dietary
      intake of cyclosporine in contrast to oral bolus dosages.
AB  - BACKGROUND: Organ transplant recipients using the immunosuppressant cyclosporine
      have an increased risk for developing nonmelanoma skin cancer. Disparate effects
      of cyclosporine have, however, been reported on UV-induced skin carcinogenesis in
      mouse experiments. Therefore, we set out to compare three experimental protocols
      using mice, with the aim to emulate most closely the increased skin cancer risk
      in organ transplant recipients. METHODS: UV carcinogenesis was performed in
      hairless SKH-1 mice by three protocols: dietary cyclosporine and daily UV
      exposures, dietary cyclosporine after a period of UV exposures, and bolus dosing
      cyclosporine by gavage and repeated UV exposures. RESULTS: Using chronic UV
      exposure, continuous dietary administration of cyclosporine was shown to inhibit
      tumor formation. Dietary cyclosporine after a period of UV exposures did not
      affect ensuing UV carcinogenesis. However, in contrast with dietary cyclosporine,
      bolus dosages of cyclosporine by gavage, resulting in strongly varying blood
      levels of cyclosporine, increased tumor development in chronically UV-exposed
      mice. There was no difference in tumor development between mice UV-irradiated
      during peak or trough levels of cyclosporine in the blood. Time-averaged levels
      in these mice were similar to those with cyclosporine in the diet. CONCLUSIONS:
      Cyclosporine in bolus doses appears to increase skin cancer development, whereas
      cyclosporine administration more evenly spread over time does not. Extrapolation
      to transplant patients suggests that the mode of administrating cyclosporine may
      be crucial for the increased skin cancer risk and that this risk might be lowered
      with a more steady release of cyclosporine in the body.

PMID- 23958927
TI  - Consensus review of best practice of transanal irrigation in adults.
AB  - STUDY DESIGN: Review article. OBJECTIVES: To provide a consensus expert review of
      the treatment modality for transanal irrigation (TAI). METHODS: A consensus group
      of specialists from a range of nations and disciplines who have experience in
      prescribing and monitoring patients using TAI worked together assimilating both
      the emerging literature and rapidly accruing clinical expertise. Consensus was
      reached by a round table discussion process, with individual members leading the
      article write-up in the sections where they had particular expertise. RESULTS:
      Detailed trouble-shooting tips and an algorithm of care to assist professionals
      with patient selection, management and follow-up was developed. CONCLUSION: This
      expert review provides a practical adjunct to training for the emerging
      therapeutic area of TAI. Careful patient selection, directly supervised training
      and sustained follow-up are key to optimise outcomes with the technique. Adopting
      a tailored, stepped approach to care is important in the heterogeneous patient
      groups to whom TAI may be applied. SPONSORSHIP: The review was financially
      supported by Coloplast A/S.

PMID- 23958928
TI  - Orexinergic innervation of urocortin1 and cocaine and amphetamine regulated
      transcript neurons in the midbrain centrally projecting Edinger-Westphal nucleus.
AB  - Orexin is a neuropeptide that has been implicated in several processes, such as
      induction of appetite, arousal and alertness and sleep/wake regulation. Multiple
      lines of evidence also suggest that orexin is involved in the stress response.
      When orexin is administered intracerebroventricular it activates the hypothalamic
      pituitary adrenal (HPA)-axis, which is the main regulator of the stress response.
      The HPA-axis is not the only player in the stress response evidence suggests that
      urocortin 1 (Ucn1), a member of the corticotropin releasing factor (CRF)
      neuropeptide family, also plays an important role in the stress response
      adaptation. Ucn1 is primarily synthetized in the centrally projecting Edinger
      Westphal nucleus (EWcp), which also receives dense innervation by orexin
      terminals. In this study we tested the hypothesis that orexin would directly
      shape the response of EWcp-Ucn1 neurons to acute cold stress. To test this
      hypothesis, we first assessed whether orexinergic axon terminals would innervate
      EWcp-Ucn1/CART neurons, and next we exposed orexin deficient (orexin-KO) male
      mice and their male wild-type (WT) littermates to acute cold stress for 2h. We
      also assessed stress-associated changes in plasma corticosterone (CORT), as well
      as the activation of Ucn1/CART neurons in the EWcp nucleus. We found that orexin
      immunoreactive axon terminals were juxtaposed to EWcp-Ucn1/CART neurons, which
      also expressed orexin receptor 1 mRNA. Furthermore, acute stress strongly
      activated the EWcp-Ucn1/CART neurons and increased plasma CORT in both WT
      littermates and orexin-KO mice, however no genotype effect was found on these
      indices. Taken together our data show that orexin in general is not involved in
      the animal's acute stress response (plasma CORT) and it does not play a direct
      role in shaping the response of EWcp-Ucn1 neurons to acute stress either. 

PMID- 23958929
TI  - Repeated injections of intradetrusor onabotulinumtoxinA as adjunctive treatment
      of children with neurogenic bladder.
AB  - AIM: To evaluate the effects of repeated injections of onabotulinumtoxinA in
      children with neurogenic bladders refractory to conventional treatment. PATIENTS
      AND METHODS: A total of 26 children with neurogenic bladder were prospectively
      studied. Some patients received up to four repeat injections. Patients were
      reinjected if they showed improvement in voiding diary, score of urinary
      incontinence and/or urodynamic studies; otherwise, augmentation cystoplasty was
      indicated. RESULTS: Of the 26 patients, 12 were reinjected a second time, 6
      patients were reinjected a third time and 2 patients received a repeat injection
      for the fourth time. Six months after the first, second and third injection, the
      urinary incontinence score 0 (dry) was 50, 77 and 75 %, respectively. After each
      injection, the mean bladder capacity in voiding diary and the mean maximum
      cystometric capacity increased. The mean detrusor pressure at the end of filling
      decreased. Only compliance after the first injection improved significantly.
      Detrusor overactivity (n: 4), improved during 3 months and reappeared in three
      children after the first injection, but at greater cystometric volumes. In the
      fourth case, it reappeared 11 months after the third injection. Five patients
      underwent cystoplasty. CONCLUSION: After treatment with onabotulinumtoxinA,
      urinary continence achieved was 50-77 %. There were favorable changes in
      urodynamic variables, but they were insufficient. Detrusor overactivity was
      attenuated, but did not disappear completely.

PMID- 23958930
TI  - Inorganic halogen ligands in quantum dots: I-, Br-, Cl- and film fabrication
      through electrophoretic deposition.
AB  - Halogen ions (I(-), Br(-), Cl(-)) were added into a colloidal solution of CdSe
      and PbS quantum dots (QDs) to form QDs capped with these inorganic ligands.
      Halogen ions attached to QDs through electrostatic interactions and the varying
      coordination strength between the inorganic ligands and QDs led to different
      degrees of redispersion and stabilization in polar solvents. Moreover, we
      successfully conducted electrophoretic deposition (EPD) of QDs capped with
      inorganic ligands. Negatively charged QDs were adsorbed onto a positively charged
      TiO2 anode. The assembled QDs films were used in photovoltaic devices and offered
      better efficiency than QDs capped with organic ligands. This work demonstrates
      that halogen ions are indeed promising ligands to improve the stability of QDs
      with inorganic ligands and the EPD method shows prospects in assembling QDs films
      for practical applications. 

PMID- 23958931
TI  - Highly regioselective synthesis of 2,4,5-(hetero)aryl substituted oxazoles by
      intermolecular [3+2]-cycloaddition of unsymmetrical internal alkynes.
AB  - A robust N-nucleophilic 1,3-N,O-dipole equivalent reacts with unsymmetrical
      internal alkynes under gold catalysis. Conjugation from a remote nitrogen lone
      pair enables and controls this convergent and highly regioselective process. 

PMID- 23958932
TI  - Reasoning about 'irrational' actions: when intentional movements cannot be
      explained, the movements themselves are seen as the goal.
AB  - Infants and adults are thought to infer the goals of observed actions by
      calculating the actions' efficiency as a means to particular external effects,
      like reaching an object or location. However, many intentional actions lack an
      external effect or external goal (e.g. dance). We show that for these actions,
      adults infer that the agents' goal is to produce the movements themselves:
      Movements are seen as the intended outcome, not just a means to an end. We test
      what drives observers to infer such movement-based goals, hypothesizing that
      observers infer movement-based goals to explain actions that are clearly
      intentional, but are not an efficient means to any plausible external goal. In
      three experiments, we separately manipulate intentionality and efficiency,
      equating for movement trajectory, perceptual features, and external effects. We
      find that participants only infer movement-based goals when the actions are
      intentional and are not an efficient means to external goals. Thus, participants
      appear to infer that movements are the goal in order to explain otherwise
      mysterious intentional actions. These findings expand models of goal inference to
      account for intentional yet 'irrational' actions, and suggest a novel explanation
      for overimitation as emulation of movement-based goals. 

PMID- 23958933
TI  - Enhancing thermopower and hole mobility in bulk p-type half-Heuslers using full
      Heusler nanostructures.
AB  - The concept of band structure engineering near the Fermi level through atomic
      scale alteration of a bulk semiconductor crystal structure using coherently
      embedded intrinsic semiconducting quantum dots provides a unique opportunity to
      manipulate the transport behavior of the existing ensembles of carriers within
      the semiconducting matrix. Here we show that in situ growth of coherent nanometer
      scale full-Heusler quantum dots (fH-QDs) within the p-type
      Ti(0.5)Hf(0.5)CoSb(0.9)Sn(0.1) half-Heusler (hH) matrix induces a drastic
      decrease of the effective hole density within the hH/fH-QD nanocomposites at 300
      K followed by a sharp increase with rising temperature. This behavior is
      associated with the formation of staggered heterojunctions with a valence band
      (VB) offset energy, DeltaE at the hH/fH phase boundaries. The energy barrier
      (DeltaE) discriminates existing holes with respect to their energy by trapping
      low energy (LE) holes, while promoting the transport of high energy (HE) holes
      through the VB of the fH-QDs. This "hole culling" results in surprisingly large
      increases in the mobility and the effective mass of HE holes contributing to
      electronic conduction. The simultaneous reduction in the density and the increase
      in the effective mass of holes resulted in large enhancements of the thermopower
      whereas; the increase in the mobility minimizes the drop in the electrical
      conductivity.

PMID- 23958934
TI  - Focus.

PMID- 23958935
TI  - The role of MDSCs in hepatocellular carcinoma--in vivo veritas?

PMID- 23958936
TI  - Non-invasive diagnosis of small nodules in cirrhosis.

PMID- 23958937
TI  - Reply to: "non-invasive diagnosis of small nodules in cirrhosis".

PMID- 23958938
TI  - FUT2 and FUT3 genotype determines CA19-9 cut-off values for detection of
      cholangiocarcinoma in patients with primary sclerosing cholangitis.
AB  - BACKGROUND & AIMS: Allelic variants of fucosyltransferases 2 and 3 (FUT2/3)
      influence serum levels of CA19-9, a screening parameter commonly used for
      detection of biliary malignancy in PSC. We aimed at improving diagnostic accuracy
      of CA19-9 by determining the impact of FUT2/3 genotypes. METHODS: CA19-9 levels
      were measured in 433 PSC patients, 41 of whom had biliary malignancy. Genotypes
      for FUT3 and FUT2 were used to assign patients to one of three groups: A, no FUT3
      activity regardless of FUT2 activity; B, both FUT2 and FUT3 activity and C, no
      FUT2 activity without loss of FUT3 activity. Group-specific cut-off values were
      determined by Youden's index. RESULTS: The median CA19-9 values of cancer-free
      patients were significantly different (p<0.001) in Groups A (2.0U/ml), B
      (17.0U/ml), and C (37.0U/ml). Biliary malignancy patients in Groups B and C had
      significantly higher CA19-9 values than cancer-free patients (p<0.001). The
      optimal cut-off, as determined by ROC analysis, for all patients was 88.5U/ml.
      Optimal cut-off values in Groups A, B, and C were 4.0U/ml, 74.5U/ml, and
      106.8U/ml, respectively. Use of these values improved sensitivity of CA19-9 in
      Groups B and C. Further, use of group-dependent cut-off values with 90%
      sensitivity resulted in a 42.9% reduction of false positive results. CONCLUSIONS:
      Use of FUT2/3 genotype-dependent cut-off values for CA19-9 improved sensitivity
      and reduced the number of false positive results.

PMID- 23958940
TI  - Carbon dot reduced palladium nanoparticles as active catalysts for carbon-carbon
      bond formation.
AB  - Carbon dots were used as a reducing agent for the synthesis of Pd nanoparticles
      coated with ultrathin carbon dot shells of ca. 4 nm. The resulting composite
      nanoparticles showed high catalytic activity for the Heck and Suzuki coupling
      reactions. 

PMID- 23958939
TI  - Body size and time-to-pregnancy in black women.
AB  - STUDY QUESTION: Are overall and central obesity associated with reduced
      fecundability in US black women? SUMMARY ANSWER: Overall and central obesity-
      based on self-reported measures of body mass index (BMI, kg/m(2)), waist
      circumference and waist-to-hip ratio--were independent risk factors for
      subfertility in our cohort. WHAT IS KNOWN ALREADY: Overall obesity (BMI >= 30
      kg/m(2)) has been associated with infertility in several studies. The role of
      central obesity is less clear. There are no previous studies of time-to-pregnancy
      (TTP) in black women. STUDY DESIGN, SIZE, DURATION: Data were derived from the
      Black Women's Health Study, a prospective cohort study. During 1995-2011, there
      were 2239 planned pregnancy attempts reported by 1697 women, resulting in 2022
      births. Cohort retention was greater than 80%. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: Eligible women were aged 21-40 years and reported at least one planned
      pregnancy attempt during 1995-2011. Height and weight were reported in 1995, with
      weight updated every two years; waist and hip circumferences were reported in
      1995 and updated in 2003. A validation study within the cohort showed high
      correlations between self-reported and technician-measured weight (r = 0.97),
      height (r = 0.93), waist circumference (r = 0.75) and hip circumference (r =
      0.74). In 2011, TTP was reported in months. Proportional probabilities regression
      models were used to estimate fecundability ratios (FRs) and 95% confidence
      intervals (CI), adjusting for covariates. MAIN RESULTS AND THE ROLE OF CHANCE:
      High BMI was associated with delayed conception: relative to BMI 18.5-24.9, FRs
      for BMI categories of <18.5, 25.0-29.9, 30.0-34.9 and >= 35.0 were 0.92 (CI: 0.64
      1.32), 0.93 (CI: 0.84-1.03), 0.92 (CI: 0.79-1.06) and 0.73 (CI: 0.61-0.87),
      respectively. Associations were stronger among nulliparous women (P-interaction =
      0.003). After controlling for BMI, reduced fecundability was observed among women
      with large waist circumferences (>= 33 versus <26 inches: FR = 0.73, CI: 0.60
      0.88) and large waist-to-hip ratios (>= 0.85 versus <0.71: FR = 0.83, CI: 0.71
      0.97). LIMITATIONS, REASONS FOR CAUTION: TTP was reported retrospectively and
      error in recall is likely, particularly as time since the pregnancy increases.
      However, results were similar when based on the most recent versus first
      pregnancies. Confounding may have been introduced by the lack of control for
      important determinants of TTP. Nevertheless, control for maternal age and
      education, which are highly correlated with TTP determinants such as paternal age
      and persistence in trying, should reduce the extent of confounding. The analysis
      was confined to planned pregnancies. If pregnancy intention was related both to
      body size and fecundability, our results could be biased. Bias is likely to be
      small because we found little difference in body size and other measured
      characteristics between pregnancy planners and non-planners. WIDER IMPLICATIONS
      OF THE FINDINGS: Our findings add to the growing body of literature showing that
      excess BMI is associated with reduced fecundability and further suggest that
      central obesity is an important independent risk factor for infertility. The
      relation of obesity to infertility is especially relevant to US black women
      because they have higher rates of obesity and infertility. Reductions in overall
      and central obesity may offer the potential to improve fertility outcomes. STUDY
      FUNDING/COMPETING INTEREST(S): This work was funded by National Cancer Institute
      grant CA58420. We have no competing interests to report.

PMID- 23958941
TI  - The antidepressant-like action of mGlu5 receptor antagonist, MTEP, in the tail
      suspension test in mice is serotonin dependent.
AB  - RATIONALE: Numerous studies indicate the potential antidepressant actions of
      several mGlu5 receptor antagonists, including 3-[(2-methyl-1,3-thiazol-4
      yl)ethynyl]-pyridine (MTEP). The explanation for the mechanism of these effects
      might be a key step in finding new antidepressant drugs (AD). OBJECTIVES: The aim
      of the present study was to investigate the possible role of the serotonergic
      system in the antidepressant-like activity of MTEP in the tail suspension test
      (TST) in C57BL/6J mice, using selected antagonists of serotonergic receptors and
      by applying two different methods of serotonin (5-HT) depletion. RESULTS: The
      results of our studies showed that the mGlu5 receptor antagonist, MTEP, similar
      to the fluoxetine used as reference AD, did not induce antidepressant-like
      effects in mice pretreated with tryptophan hydroxylase inhibitor,
      parachlorophenylalanine. On the other hand, MTEP worked as a potential AD in the
      TST in mice fed on a tryptophan-free (TRP-free) diet for 3 weeks. However,
      fluoxetine, which was used as a reference control was also active in this
      experiment, suggesting that a TRP-free diet was not sufficiently effective in
      reducing the 5-HT level. Furthermore, we showed that the 5HT2A/2C antagonist,
      ritanserin, yet not the 5-HT1A antagonist, WAY100635, 5HT1B antagonist, SB224289
      or 5HT4 antagonist, GR125487, reversed the antidepressant-like effects of MTEP in
      the TST. Finally, a sub-effective dose ofMTEP coadministered with a sub-effective
      dose of citalopram induced an antidepressant-like effect in the TST in mice.
      CONCLUSION: The results of our studies suggest the involvement of serotonergic
      system activation in the antidepressant-like effects of the mGlu5 antagonist,
      MTEP, in the TST in mice.

PMID- 23958942
TI  - Mining mouse behavior for patterns predicting psychiatric drug classification.
AB  - RATIONALE: In psychiatric drug discovery, a critical step is predicting the
      psychopharmacological effect and therapeutic potential of novel (or repurposed)
      compounds early in the development process. This process is hampered by the need
      to utilize multiple disorder-specific and labor-intensive behavioral assays.
      OBJECTIVES: This study aims to investigate the feasibility of a single high
      throughput behavioral assay to classify psychiatric drugs into multiple
      psychopharmacological classes. METHODS: Using Pattern Array, a procedure for data
      mining exploratory behavior in mice, we mined ~100,000 complex movement patterns
      for those that best predict psychopharmacological class and dose. The best
      patterns were integrated into a classification model that assigns
      psychopharmacological compounds to one of six clinically relevant classes-
      antipsychotic, antidepressant, opioids, psychotomimetic, psychomotor stimulant,
      and alpha-adrenergic. RESULTS: Surprisingly, only a small number of well-chosen
      behaviors were required for successful class prediction. One of them, a behavior
      termed "universal drug detector", was dose-dependently decreased by drugs from
      all classes, thus providing a sensitive index of psychopharmacological activity.
      In independent validation in a blind fashion, simulating the process of in vivo
      pre-clinical drug screening, the classification model correctly classified nine
      out of 11 "unknown" compounds. Interestingly, even "misclassifications" match
      known alternate therapeutic indications, illustrating drug "repurposing"
      potential. CONCLUSIONS: Unlike standard animal models, the discovered
      classification model can be systematically updated to improve its predictive
      power and add therapeutic classes and subclasses with each additional
      diversification of the database. Our study demonstrates the power of data mining
      approaches for behavior analysis, using multiple measures in parallel for drug
      screening and behavioral phenotyping.

PMID- 23958943
TI  - Role of alpha5* nicotinic acetylcholine receptors in the effects of acute and
      chronic nicotine treatment on brain reward function in mice.
AB  - OBJECTIVE: Allelic variation in the alpha5 nicotinic acetylcholine receptor
      (nAChR) subunit gene, CHRNA5, increases vulnerability to tobacco addiction. Here,
      we investigated the role of alpha5* nAChRs in the effects of nicotine on brain
      reward systems. MATERIALS AND METHODS: Effects of acute (0.03125-0.5 mg/kg SC) or
      chronic (24 mg/kg per day; osmotic minipump) nicotine and mecamylamine
      precipitated withdrawal on intracranial self-stimulation (ICSS) thresholds were
      assessed in wild-type and alpha5 nAChR subunit knockout mice. Noxious effects of
      nicotine were further investigated using a conditioned taste aversion procedure.
      RESULTS: Lower nicotine doses (0.03125-0.125 mg/kg) decreased ICSS thresholds in
      wild-type and alpha5 knockout mice. At higher doses (0.25-0.5 mg/kg), threshold
      lowering effects of nicotine were diminished in wild-type mice, whereas nicotine
      lowered thresholds across all doses tested in alpha5 knockout mice. Nicotine (1.5
      mg/kg) conditioned a taste aversion to saccharine equally in both genotypes.
      Mecamylamine (5 mg/kg) elevated ICSS thresholds by a similar magnitude in wild
      type and alpha5 knockout mice prepared with minipumps delivering nicotine.
      Unexpectedly, mecamylamine also elevated thresholds in saline-treated alpha5
      knockout mice. CONCLUSION: alpha5* nAChRs are not involved in reward-enhancing
      effects of lower nicotine doses, the reward-inhibiting effects of nicotine
      withdrawal, or the general noxious effects of higher nicotine doses. Instead,
      alpha5* nAChRs regulate the reward-inhibiting effects nicotine doses that oppose
      the reward-facilitating effects of the drug. These data suggest that disruption
      of alpha5* nAChR signaling greatly expands the range of nicotine doses that
      facilitate brain reward activity, which may help explain the increased tobacco
      addiction vulnerability associated with CHRNA5 risk alleles.

PMID- 23958944
TI  - Xanthoceraside attenuates tau hyperphosphorylation and cognitive deficits in
      intracerebroventricular-streptozotocin injected rats.
AB  - RATIONALE: Xanthoceraside, a novel triterpenoid saponin extracted from the fruit
      husks of Xanthoceras sorbifolia Bunge, reverses cognitive deficits in
      intracerebroventricular injection of Abeta25-35 or Abeta1-42 mice. However,
      whether xanthoceraside has a positive effect on hyperphosphorylated tau protein
      remains unclear. OBJECTIVES: We investigated the effects of xanthoceraside on
      behavioural impairments induced by intracerebroventricular injection of
      streptozotocin (STZ) in rats and its potential mechanisms. MATERIALS AND METHODS:
      The rats were administered with xanthoceraside (0.06, 0.12 or 0.24 mg/kg) or
      vehicle once daily after STZ intracerebroventricular injections. The Y-maze test
      and novel object recognition test were performed 21 and 22 days after the second
      STZ injection, respectively. The levels of hyperphosphorylated tau,
      phosphatidylinositol-3-kinase (PI3K)/serine/threonine protein kinase B (Akt),
      glycogen synthase kinase-3beta (GSK-3beta), protein phosphatase 1 (PP-1) and
      protein phosphatase 2A (PP-2A) were also tested by Western blot. RESULTS:
      Xanthoceraside treatment significantly attenuated learning and memory impairments
      and reduced the level of STZ-induced hyperphosphorylated tau protein.
      Xanthoceraside also enhanced PP-2A and PP-1 expressions, increased PI3K (p85) and
      Akt (Ser473) phosphorylation and decreased GSK-3beta (tyr216) phosphorylation.
      CONCLUSIONS: Xanthoceraside has protective effect against learning and memory
      impairments and inhibits tau hyperphosphorylation in the hippocampus, possibly
      through the inhibition of the PI3K/Akt-dependent GSK-3beta signalling pathway and
      an enhancement of phosphatases activity.

PMID- 23958945
TI  - Treatment of first-episode non-affective psychosis: a randomized comparison of
      aripiprazole, quetiapine and ziprasidone over 1 year.
AB  - RATIONALE: Discontinuation of antipsychotic treatment at early phases increases
      the risk of poor adherence to maintenance drug therapy. Differences among
      antipsychotics in terms of effectiveness may determine a good adherence to
      treatment. OBJECTIVES: The aim of this study is to compare the clinical
      effectiveness of aripiprazole, ziprasidone and quetiapine in the treatment of
      first-episode schizophrenia spectrum disorders at 1 year. METHOD: From October
      2005 to January 2011 a prospective, randomized, open-label study was undertaken.
      Two hundred two first-episode drug-naive patients were randomly assigned to
      aripiprazole (N = 78), ziprasidone (N = 62), or quetiapine (N = 62) and followed
      up for 1 year. The primary effectiveness measure was all-cause of treatment
      discontinuation. In addition, an analysis based on intention-to-treat principle
      was conducted in the analysis for clinical efficacy. RESULTS: The overall dropout
      rate at 1 year was 13.37 %. The treatment discontinuation rate differed
      significantly between treatment groups (aripiprazole = 43.6 %, ziprasidone = 66.1
      % and quetiapine = 82.3 %) (chi 2 = 22.545; p < 0.001). Insufficient efficacy in
      the group of quetiapine is the most important reason for differences in
      discontinuation rates between agents (chi 2 = 19.436; p < 0.001). The mean time
      to all-cause discontinuation was significantly different between groups (LogRank
      = 30.732 p < 0.001). The profile of extrapyramidal symptoms varies between
      treatments. Patients on ziprasidone were more likely to be prescribed
      antidepressants. CONCLUSIONS: First episode patients treated with quetiapine have
      a higher risk of treatment discontinuation at midterm due to insufficient
      efficacy. Establishing differences between SGAs may help clinicians on
      prescribing decision for treatment of individuals presenting with first-episode
      non-affective psychosis.

PMID- 23958946
TI  - The first finding of chromosome variations in wild-born western hoolock gibbons.
AB  - Hoolock gibbons (genus Hoolock) are a group of very endangered primate species
      that belong to the small ape family (family Hylobatidae). The entire population
      that is distributed in the northeast and southeast of Bangladesh is estimated to
      include only around 350 individuals. A conservation program is thus necessary as
      soon as possible. Genetic markers are significant tools for planning such
      programs. In this study, we examined chromosomal characteristics of two western
      hoolock gibbons that were captured in a Bangladesh forest. During chromosome
      analysis, we encountered two chromosome variations that were observed for the
      first time in the wild-born western hoolock gibbons (Hoolock hoolock). The first
      one was a nonhomologous centromere position in chromosome 8 that was observed in
      the two examined individuals. The alteration was identical in the two
      individuals, which were examined by G-band and DAPI-band analyses. Chromosome
      paint analyses revealed that the difference in the centromere position was due to
      a single small pericentric inversion. The second variation was a heterozygous
      elongation in chromosome 9. Analysis by sequential techniques of fluorescence in
      situ hybridization with 18S rDNA and silver nitrate staining revealed a single
      and an inverted tandem duplication, respectively, of the nucleolus organizer
      region in two individuals. These chromosome variations provide useful information
      for the next steps to consider the evolution and conservation of the hoolock
      gibbon.

PMID- 23958947
TI  - Optimization via specific fluorescence brightness of a receptor-targeted probe
      for optical imaging and positron emission tomography of sentinel lymph nodes.
AB  - The optical properties of a receptor-targeted probe designed for dual-modality
      mapping of the sentinel lymph node (SLN) was optimized. Specific fluorescence
      brightness was used as the design criterion, which was defined as the
      fluorescence brightness per mole of the contrast agent. Adjusting the molar ratio
      of the coupling reactants, IRDye 800CW-NHS-ester and tilmanocept, enabled us to
      control the number of fluorescent molecules attached to each tilmanocept, which
      was quantified by H1 nuclear magnetic resonance spectroscopy. Quantum yields and
      molar absorptivities were measured for unconjugated IRDye 800CW and IRDye 800CW
      tilmanocept (800CW-tilmanocept) preparations at 0.7, 1.5, 2.3, 2.9, and 3.8 dyes
      per tilmanocept. Specific fluorescence brightness was calculated by
      multiplication of the quantum yield by the molar absorptivity and the number of
      dyes per tilmanocept. It predicted that the preparation with 2.3 dyes per
      tilmanocept would exhibit the brightest signal, which was confirmed by
      fluorescence intensity measurements using three optical imaging systems. When
      radiolabeled with Ga68 and injected into the footpads of mice, the probe
      identified SLNs by both fluorescence and positron emission tomography (PET) while
      maintaining high percent extraction by the SLN. These studies demonstrated the
      feasibility of 800CW-tilmanocept for multimodal SLN mapping via fluorescence and
      PET-computed tomography imaging.

PMID- 23958948
TI  - Salivary protein markers: a noninvasive protein profile-based method for the
      early diagnosis of oral premalignancy and malignancy.
AB  - An ultra-sensitive hyphenated technique, high-performance liquid chromatography
      laser-induced fluorescence detection protein profiling of saliva, is evaluated
      for early detection and diagnosis of oral premalignancy and malignancy.
      Calibration sets of protein profiles of unstimulated whole saliva are collected
      from clinically/pathologically normal, premalignant, and malignant subjects and
      used as standards. Three parameters-scores of factors, sum of squared residuals,
      and Mahalanobis distance-derived from principal component analysis of protein
      profiles of the standard calibration sets, and blind samples are used for
      "match/no-match" diagnosis of the blind samples. Analyses of the results show
      that the method is capable of differentiating normal, premalignant, and malignant
      conditions with the sensitivity and specificity of 79% and 78%, respectively. The
      technique provides a fast, highly objective (free from personal judgment and
      statistically defined), and noninvasive diagnostic method for screening and early
      detection of oral cancer.

PMID- 23958949
TI  - Denileukin diftitox (ONTAK) induces a tolerogenic phenotype in dendritic cells
      and stimulates survival of resting Treg.
AB  - Denileukin diftitox (DD), a diphtheria toxin fragment IL-2 fusion protein, is
      thought to target and kill CD25(+) cells. It is approved for the treatment of
      cutaneous T-cell lymphoma and is used experimentally for the depletion of
      regulatory T cells (Treg) in cancer trials. Curiously enough, clinical effects of
      DD did not strictly correlate with CD25 expression, and Treg depletion was not
      confirmed unambiguously. Here, we report that patients with melanoma receiving DD
      immediately before a dendritic cell (DC) vaccine failed to develop a tumor
      antigen-specific CD4 and CD8 T-cell immune response even after repeated
      vaccinations. Analyzing the underlying mechanism, so far we found unknown effects
      of DD. First, DD modulated DCs toward tolerance by downregulating costimulatory
      receptors such as CD83 and CD25 while upregulating tolerance-associated
      proteins/pathways including Stat-3, beta-catenin, and class II transactivator
      dependent antigen presentation. Second, DD blocked Stat3 phosphorylation in
      maturing DCs. Third, only activated, but not resting, Treg internalized DD and
      were killed. Conversely, resting Treg showed increased survival because of DD
      mediated antiapoptotic IL-2 signaling. We conclude that DD exerts functions
      beyond CD25(+) cell killing that may affect their clinical use and could be
      tested for novel indications.

PMID- 23958950
TI  - Long-term health-related quality of life evaluated more than 20 years after
      hematopoietic stem cell transplantation for thalassemia.
AB  - The principal aim of our study was to investigate whether patients transplanted
      more than 20 years ago for beta-thalassemia major had a different health-related
      quality of life (HRQoL) compared with the general population. The Medical
      Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the Functional
      Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) were received from
      109 ex-thalassemia patients who underwent hematopoietic stem cell transplantation
      (HSCT) during the 1980s and 1990s. Adjusted comparisons were performed separately
      for patient age at HSCT and the presence or absence of graft-versus-host disease
      (GVHD). Sociodemographic and clinical variables were also analyzed. The median
      age of our cohort at HSCT and the time of the survey was 12 years (range, 1-36)
      and 34 years (range, 21-48), respectively, with a median follow-up age of 22.8
      years (range, 11.7-30.3). Statistical analysis of data collected more than 20
      years after HSCT showed that the long-term HRQoL of ex-thalassemia patients was
      very similar to that of the general population. Clinical meaningful differences
      were only found for the general health (GH) scale (-8.9; 95% CI, -15.0 to 2.7, P
      = .005). Mental health, education level, employment status, marital status,
      living arrangements, and birth rate were compatible with normal living patterns.
      The development of GVHD and older age at transplantation were important impairing
      factors. Additional analyses performed to evaluate HRQoL in an age-sex-matched
      cohort of 124 patients receiving conventional treatment of beta-thalassemia
      revealed poorer outcomes compared with the cohort of transplanted patients. 

PMID- 23958951
TI  - Identification of a cellular ligand for the natural cytotoxicity receptor NKp44.
AB  - With an array of activating and inhibitory receptors, natural killer (NK) cells
      are involved in the eradication of infected, transformed, and tumor cells. NKp44
      is a member of the natural cytotoxicity receptor family, which is exclusively
      expressed on activated NK cells. Here, we identify natural cytotoxicity receptor
      NKp44 (NKp44L), a novel isoform of the mixed-lineage leukemia-5 protein, as a
      cellular ligand for NKp44. Unlike the other MLL family members, NKp44L is
      excluded from the nucleus, but expressed at the cell-surface level; its
      subcellular localization is being associated with the presence of a specific C
      terminal motif. Strikingly, NKp44L has not been detected on circulating cells
      isolated from healthy individuals, but it is expressed on a large panel of the
      tumor and transformed cells. The sharply decreased NK lysis activity induced by
      anti-NKp44L antibodies directly demonstrates the role of NKp44L in cytotoxicity.
      Taken together, these results show that NKp44L could be critical for NK cell
      mediated innate immunity. The identification and cellular distribution of NKp44L
      highlight the role of this self-molecule as a danger signal to alert the NK cell
      network. 

PMID- 23958952
TI  - Requirement for Rictor in homeostasis and function of mature B lymphoid cells.
AB  - The mammalian target of rapamycin (mTOR), an essential serine/threonine kinase,
      functions in biochemically distinct multiprotein complexes, but little is known
      about roles of the complexes in B cells. The acutely rapamycin-sensitive mTOR
      complex 1 (mTORC1) is defined by a core subunit Raptor, whereas mTORC2 lacks
      Raptor and, instead, has Rictor and SIN1 as distinct essential components. We now
      show that homeostasis and function of B cells require Rictor. Conditional
      deletion of Rictor before lymphoid specification impaired generation of mature
      follicular, marginal zone, and B1a B lymphocytes. Induced inactivation in adult
      mice caused cell-autonomous defects in B lymphoid homeostasis and antibody
      responses in vivo, along with affecting plasma cells in bone marrow. Survival of
      B lymphocytes depended on Rictor, which was vital for normal induction of
      prosurvival genes, suppression of proapoptotic genes, nuclear factor kappaB
      induction after B-cell receptor stimulation, and B-cell activating factor-induced
      nuclear factor kappaB2/p52 generation. Collectively, the findings provide
      evidence that mTOR signaling affects survival and proliferation of mature B
      lymphocytes, and establish Rictor as an important signal relay in B-cell
      homeostasis, fate, and functions. 

PMID- 23958953
TI  - Comprehensive mutational profiling in advanced systemic mastocytosis.
AB  - To explore mechanisms contributing to the clinical heterogeneity of systemic
      mastocytosis (SM) and to suboptimal responses to diverse therapies, we analyzed
      39 KIT D816V mutated patients with indolent SM (n = 10), smoldering SM (n = 2),
      SM with associated clonal hematologic nonmast cell lineage disorder (SM-AHNMD, n
      = 5), and aggressive SM (n = 15) or mast cell leukemia (n = 7) with (n = 18) or
      without (n = 4) AHNMD for additional molecular aberrations. We applied next
      generation sequencing to investigate ASXL1, CBL, IDH1/2, JAK2, KRAS, MLL-PTD,
      NPM1, NRAS, TP53, SRSF2, SF3B1, SETBP1, U2AF1 at mutational hotspot regions, and
      analyzed complete coding regions of EZH2, ETV6, RUNX1, and TET2. We identified
      additional molecular aberrations in 24/27 (89%) patients with advanced SM (SM
      AHNMD, 5/5; aggressive SM/mast cell leukemia, 19/22) whereas only 3/12 (25%)
      indolent SM/smoldering SM patients carried one additional mutation each (U2AF1,
      SETBP1, CBL) (P < .001). Most frequently affected genes were TET2, SRSF2, ASXL1,
      CBL, and RUNX1. In advanced SM, 21/27 patients (78%) carried >=3 mutations, and
      11/27 patients (41%) exhibited >=5 mutations. Overall survival was significantly
      shorter in patients with additional aberrations as compared to those with KIT
      D816V only (P = .019). We conclude that biology and prognosis in SM are related
      to the pattern of mutated genes that are acquired during disease evolution. 

PMID- 23958954
TI  - Small RNA-mediated regulation of host-pathogen interactions.
AB  - The rise in antimicrobial drug resistance, alongside the failure of conventional
      research to discover new antibiotics, will inevitably lead to a public health
      crisis that can drastically curtail our ability to combat infectious disease.
      Thus, there is a great global health need for development of antimicrobial
      countermeasures that target novel cell molecules or processes. RNA represents a
      largely unexploited category of potential targets for antimicrobial design. For
      decades, control of cellular behavior was thought to be the exclusive purview of
      protein-based regulators. The recent discovery of small RNAs (sRNAs) as a
      universal class of powerful RNA-based regulatory biomolecules has the potential
      to revolutionize our understanding of gene regulation in practically all
      biological functions. In general, sRNAs regulate gene expression by base-pairing
      with multiple downstream target mRNAs to prevent translation of mRNA into
      protein. In this review, we will discuss recent studies that document discovery
      of bacterial, viral, and human sRNAs and their molecular mechanisms in regulation
      of pathogen virulence and host immunity. Illuminating the functional roles of
      sRNAs in virulence and host immunity can provide the fundamental knowledge for
      development of next-generation antibiotics using sRNAs as novel targets. 

PMID- 23958955
TI  - Repeated exposure to MDMA triggers long-term plasticity of noradrenergic and
      serotonergic neurons.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA or 'ecstasy') is a psychostimulant drug,
      widely used recreationally among young people in Europe and North America.
      Although its neurotoxicity has been extensively described, little is known about
      its ability to strengthen neural circuits when administered in a manner that
      reproduces human abuse (i.e. repeated exposure to a low dose). C57BL/6J mice were
      repeatedly injected with MDMA (10 mg kg(-1), intraperitoneally) and studied after
      a 4-day or a 1-month withdrawal. We show, using in vivo microdialysis and
      locomotor activity monitoring, that repeated injections of MDMA induce a long
      term sensitization of noradrenergic and serotonergic neurons, which correlates
      with behavioral sensitization. The development of this phenomenon, which lasts
      for at least 1 month after withdrawal, requires repeated stimulation of alpha(1B)
      adrenergic and 5-hydroxytryptamine (5-HT)(2A) receptors. Moreover, behavioral and
      neuroendocrine assays indicate that hyper-reactivity of noradrenergic and
      serotonergic networks is associated with a persistent desensitization of
      somatodendritic alpha(2A)-adrenergic and 5-HT1A autoreceptor function. Finally,
      molecular analysis including radiolabeling, western blot and quantitative reverse
      transcription-polymerase chain reaction reveals that mice repeatedly treated with
      MDMA exhibit normal alpha(2A)-adrenergic and 5-HT(1A) receptor binding, but a
      long-lasting downregulation of Galphai proteins expression in both locus
      coeruleus and dorsal raphe nucleus. Altogether, our results show that repeated
      MDMA exposure causes strong neural and behavioral adaptations and that inhibitory
      feedback mediated by alpha(2A)-adrenergic and 5-HT(1A) autoreceptors has an
      important role in the physiopathology of addictive behaviors.

PMID- 23958958
TI  - Amount of lifetime video gaming is positively associated with entorhinal,
      hippocampal and occipital volume.
AB  - Playing video games is a popular leisure activity among children and adults, and
      may therefore potentially influence brain structure. We have previously shown a
      positive association between probability of gray matter (GM) volume in the
      ventral striatum and frequent video gaming in adolescence. Here we set out to
      investigate structural correlates of video gaming in adulthood, as the effects
      observed in adolescents may reflect only a fraction of the potential neural long
      term effects seen in adults. On magnetic resonance imaging (MRI) scans of 62 male
      adults, we computed voxel-based morphometry to explore the correlation of GM with
      the lifetime amount of video gaming (termed joystick years). We found a
      significant positive association between GM in bilateral parahippocamal region
      (entorhinal cortex) and left occipital cortex/inferior parietal lobe and joystick
      years (P<0.001, corrected for multiple comparisons). An exploratory analysis
      showed that the entorhinal GM volume can be predicted by the video game genres
      played, such as logic/puzzle games and platform games contributing positively,
      and action-based role-playing games contributing negatively. Furthermore,
      joystick years were positively correlated with hippocampus volume. The
      association of lifetime amount of video game playing with bilateral entorhinal
      cortex, hippocampal and occipital GM volume could reflect adaptive neural
      plasticity related to navigation and visual attention. 

PMID- 23958957
TI  - Serum BDNF concentrations as peripheral manifestations of depression: evidence
      from a systematic review and meta-analyses on 179 associations (N=9484).
AB  - Meta-analyses, published in 2008-2010, have confirmed abnormally low serum brain
      derived neurotrophic factor (BDNF) concentrations in depressed patients and
      normalization of this by antidepressant treatment. These findings are believed to
      reflect peripheral manifestations of the neurotrophin hypothesis, which states
      that depression is secondary to an altered expression of BDNF in the brain. Since
      the publication of these meta-analyses, the field has seen a huge increase in
      studies on these topics. This motivated us to update the evidence on the
      aforementioned associations and, in addition, to compile the data on serum BDNF
      concentrations in relation to the symptom severity of depression. Using a
      manifold of data as compared with earlier meta-analyses, we find low serum BDNF
      concentrations in 2384 antidepressant-free depressed patients relative to 2982
      healthy controls and to 1249 antidepressant-treated depressed patients (Cohen's
      d=-0.71 and -0.56, P-values <0.0000001). When publication bias is accounted for,
      these effect-sizes become substantially smaller (d=-0.47 and -0.34, respectively,
      P-values<0.0001). We detect between-study heterogeneity in outcomes for which
      only year of publication and sample size are significant moderators, with more
      recent papers and larger samples sizes in general being associated with smaller
      between-group differences. Finally, the aggregated data negate consistent
      associations between serum BDNF concentrations and the symptom severity of
      depression. Our findings corroborate the claim that altered serum BDNF
      concentrations are peripheral manifestations of depression. However, here we
      highlight that the evidence for this claim is slimmer as was initially thought
      and amidst a lot of noise. 

PMID- 23958959
TI  - Brain-reactive IgG correlates with autoimmunity in mothers of a child with an
      autism spectrum disorder.
AB  - It is believed that in utero environmental factors contribute to autism spectrum
      disorder (ASD). The goal of this study was to demonstrate, using the largest
      cohort reported so far, that mothers of an ASD child have an elevated frequency
      of anti-brain antibodies and to assess whether brain reactivity is associated
      with an autoimmune diathesis of the mother. We screened plasma of 2431 mothers of
      an ASD child from Simon Simplex Collection and plasma of 653 unselected women of
      child-bearing age for anti-brain antibodies using immunohistology on mouse brain.
      Positive and negative plasma from mothers with an ASD child were analyzed for
      anti-nuclear antibodies and for autoimmune disorders. Mothers of an ASD child
      were four times more likely to harbor anti-brain antibodies than unselected women
      of child-bearing age (10.5 vs 2.6%). A second cohort from The Autism Genetic
      Resource Exchange with multiplex families displayed an 8.8% prevalence of anti
      brain antibodies in the mothers of these families. Fifty-three percent of these
      mothers with anti-brain antibodies also exhibited anti-nuclear autoantibodies
      compared with 13.4% of mothers of an ASD child without anti-brain antibodies and
      15% of control women of child-bearing age. The analysis of ASD mothers with brain
      reactive antibodies also revealed an increased prevalence of autoimmune diseases,
      especially rheumatoid arthritis and systemic lupus erythematosus. This study
      provides robust evidence that brain-reactive antibodies are increased in mothers
      of an ASD child and may be associated with autoimmunity. The current study serves
      as a benchmark and justification for studying the potential pathogenicity of
      these antibodies on the developing brain. The detailed characterization of the
      specificity of these antibodies will provide practical benefits for the
      management and prevention of this disorder. 

PMID- 23958956
TI  - Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility
      gene.
AB  - Genes that are differentially expressed between schizophrenia patients and
      healthy controls may have key roles in the pathogenesis of schizophrenia. We
      analyzed two large-scale genome-wide expression studies, which examined changes
      in gene expression in schizophrenia patients and their matched controls. We found
      calcium/calmodulin (CAM)-dependent protein kinase kinase 2 (CAMKK2) is
      significantly downregulated in individuals with schizophrenia in both studies. To
      seek the potential genetic variants that may regulate the expression of CAMKK2,
      we investigated the association between single-nucleotide polymorphisms (SNPs)
      within CAMKK2 and the expression level of CAMKK2. We found one SNP, rs1063843,
      which is located in intron 17 of CAMKK2, is strongly associated with the
      expression level of CAMKK2 in human brains (P=1.1 * 10(-6)) and lymphoblastoid
      cell lines (the lowest P=8.4 * 10(-6)). We further investigated the association
      between rs1063843 and schizophrenia in multiple independent populations (a total
      of 130 623 subjects) and found rs1063843 is significantly associated with
      schizophrenia (P=5.17 * 10(-5)). Interestingly, we found the T allele of
      rs1063843, which is associated with lower expression level of CAMKK2, has a
      higher frequency in individuals with schizophrenia in all of the tested samples,
      suggesting rs1063843 may be a causal variant. We also found that rs1063843 is
      associated with cognitive function and personality in humans. In addition,
      protein-protein interaction (PPI) analysis revealed that CAMKK2 participates in a
      highly interconnected PPI network formed by top schizophrenia genes, which
      further supports the potential role of CAMKK2 in the pathogenesis of
      schizophrenia. Taken together, these converging lines of evidence strongly
      suggest that CAMKK2 may have pivotal roles in schizophrenia susceptibility. 

PMID- 23958960
TI  - Response of the MU-opioid system to social rejection and acceptance.
AB  - The endogenous opioid system, which alleviates physical pain, is also known to
      regulate social distress and reward in animal models. To test this hypothesis in
      humans (n=18), we used an MU-opioid receptor (MOR) radiotracer to measure changes
      in MOR availability in vivo with positron emission tomography during social
      rejection (not being liked by others) and acceptance (being liked by others).
      Social rejection significantly activated the MOR system (i.e., reduced receptor
      availability relative to baseline) in the ventral striatum, amygdala, midline
      thalamus and periaqueductal gray (PAG). This pattern of activation is consistent
      with the hypothesis that the endogenous opioids have a role in reducing the
      experience of social pain. Greater trait resiliency was positively correlated
      with MOR activation during rejection in the amygdala, PAG and subgenual anterior
      cingulate cortex (sgACC), suggesting that MOR activation in these areas is
      protective or adaptive. In addition, MOR activation in the pregenual ACC was
      correlated with reduced negative affect during rejection. In contrast, social
      acceptance resulted in MOR activation in the amygdala and anterior insula, and
      MOR deactivation in the midline thalamus and sgACC. In the left ventral striatum,
      MOR activation during acceptance predicted a greater desire for social
      interaction, suggesting a role for the MOR system in social reward. The ventral
      striatum, amygdala, midline thalamus, PAG, anterior insula and ACC are rich in
      MORs and comprise a pathway by which social cues may influence mood and
      motivation. MOR regulation of this pathway may preserve and promote emotional
      well being in the social environment. 

PMID- 23958964
TI  - Features of computerized clinical decision support systems supportive of nursing
      practice: a literature review.
AB  - This study aimed to organize the system features of decision support technologies
      targeted at nursing practice into assessment, problem identification, care plans,
      implementation, and outcome evaluation. It also aimed to identify the range of
      the five stage-related sequential decision supports that computerized clinical
      decision support systems provided. MEDLINE, CINAHL, and EMBASE were searched. A
      total of 27 studies were reviewed. The system features collected represented the
      characteristics of each category from patient assessment to outcome evaluation.
      Several features were common across the reviewed systems. For the sequential
      decision support, all of the reviewed systems provided decision support in
      sequence for patient assessment and care plans. Fewer than half of the systems
      included problem identification. There were only three systems operating in an
      implementation stage and four systems in outcome evaluation. Consequently, the
      key steps for sequential decision support functions were initial patient
      assessment, problem identification, care plan, and outcome evaluation. Providing
      decision support in such a full scope will effectively help nurses' clinical
      decision making. By organizing the system features, a comprehensive picture of
      nursing practice-oriented computerized decision support systems was obtained;
      however, the development of a guideline for better systems should go beyond the
      scope of a literature review. 

PMID- 23958965
TI  - Nursing student control over using a computer simulation program about empowering
      discourse.
AB  - Nurses find empowering discourse as a patient education intervention demanding,
      so using methods that support the constructive learning of empowering discourse
      during their education would be helpful. The aim of this descriptive, comparative
      study was to evaluate student control when using a computer simulation program
      that facilitates learning about empowering discourse. The study hypothesis was as
      follows: Students can control the use of an empowering discourse computer
      simulation program regardless of their sociodemographic background and study
      orientation. In the study, 69 students completed an educational session
      culminating in a computer simulation in which the students responded to a
      simulated patient's statements in their choice of six content areas in three
      sections by using a multiple-choice method, an open-ended method, or both
      methods. The students used all the options in the program despite their
      background and study orientations. The findings provided evidence that nursing
      students had control over the use of the computer simulation program to manage
      their own learning and were able to construct personal knowledge about empowering
      discourse using the computer simulation regardless of their study orientations. 

PMID- 23958961
TI  - Discovery and validation of blood biomarkers for suicidality.
AB  - Suicides are a leading cause of death in psychiatric patients, and in society at
      large. Developing more quantitative and objective ways (biomarkers) for
      predicting and tracking suicidal states would have immediate practical
      applications and positive societal implications. We undertook such an endeavor.
      First, building on our previous blood biomarker work in mood disorders and
      psychosis, we decided to identify blood gene expression biomarkers for
      suicidality, looking at differential expression of genes in the blood of subjects
      with a major mood disorder (bipolar disorder), a high-risk population prone to
      suicidality. We compared no suicidal ideation (SI) states and high SI states
      using a powerful intrasubject design, as well as an intersubject case-case
      design, to generate a list of differentially expressed genes. Second, we used a
      comprehensive Convergent Functional Genomics (CFG) approach to identify and
      prioritize from the list of differentially expressed gene biomarkers of relevance
      to suicidality. CFG integrates multiple independent lines of evidence-genetic and
      functional genomic data-as a Bayesian strategy for identifying and prioritizing
      findings, reducing the false-positives and false-negatives inherent in each
      individual approach. Third, we examined whether expression levels of the blood
      biomarkers identified by us in the live bipolar subject cohort are actually
      altered in the blood in an age-matched cohort of suicide completers collected
      from the coroner's office, and report that 13 out of the 41 top CFG scoring
      biomarkers (32%) show step-wise significant change from no SI to high SI states,
      and then to the suicide completers group. Six out of them (15%) remained
      significant after strict Bonferroni correction for multiple comparisons. Fourth,
      we show that the blood levels of SAT1 (spermidine/spermine N1-acetyltransferase
      1), the top biomarker identified by us, at the time of testing for this study,
      differentiated future as well as past hospitalizations with suicidality, in a
      live cohort of bipolar disorder subjects, and exhibited a similar but weaker
      pattern in a live cohort of psychosis (schizophrenia/schizoaffective disorder)
      subjects. Three other (phosphatase and tensin homolog (PTEN), myristoylated
      alanine-rich protein kinase C substrate (MARCKS), and mitogen-activated protein
      kinase kinase kinase 3 (MAP3K3)) of the six biomarkers that survived Bonferroni
      correction showed similar but weaker effects. Taken together, the prospective and
      retrospective hospitalization data suggests SAT1, PTEN, MARCKS and MAP3K3 might
      be not only state biomarkers but trait biomarkers as well. Fifth, we show how a
      multi-dimensional approach using SAT1 blood expression levels and two simple
      visual-analog scales for anxiety and mood enhances predictions of future
      hospitalizations for suicidality in the bipolar cohort (receiver-operating
      characteristic curve with area under the curve of 0.813). Of note, this simple
      approach does not directly ask about SI, which some individuals may deny or
      choose not to share with clinicians. Lastly, we conducted bioinformatic analyses
      to identify biological pathways, mechanisms and medication targets. Overall,
      suicidality may be underlined, at least in part, by biological mechanisms related
      to stress, inflammation and apoptosis. 

PMID- 23958962
TI  - Genome-wide association study of cocaine dependence and related traits: FAM53B
      identified as a risk gene.
AB  - We report a genome-wide association study (GWAS) for cocaine dependence (CD) in
      three sets of African- and European-American subjects (AAs and EAs, respectively)
      to identify pathways, genes and alleles important in CD risk. The discovery GWAS
      data set (n=5697 subjects) was genotyped using the Illumina OmniQuad microarray
      (8 90 000 analyzed single-nucleotide polymorphisms (SNPs)). Additional genotypes
      were imputed based on the 1000 Genomes reference panel. Top-ranked findings were
      evaluated by incorporating information from publicly available GWAS data from
      4063 subjects. Then, the most significant GWAS SNPs were genotyped in 2549
      independent subjects. We observed one genome-wide-significant (GWS) result:
      rs2629540 at the FAM53B ('family with sequence similarity 53, member B') locus.
      This was supported in both AAs and EAs; P-value (meta-analysis of all
      samples)=4.28 * 10(-8). The gene maps to the same chromosomal region as the
      maximum peak we observed in a previous linkage study. NCOR2 (nuclear receptor
      corepressor 2) SNP rs150954431 was associated with P=1.19 * 10(-9) in the EA
      discovery sample. SNP rs2456778, which maps to CDK1 ('cyclin-dependent kinase
      1'), was associated with cocaine-induced paranoia in AAs in the discovery sample
      only (P=4.68 * 10(-8)). This is the first study to identify risk variants for CD
      using GWAS. Our results implicate novel risk loci and provide insights into
      potential therapeutic and prevention strategies. 

PMID- 23958966
TI  - Telecare for diabetes mellitus: case managers' experiences.
AB  - Diabetes is a metabolic disorder that, if not treated promptly and appropriately,
      can cause complex health complications and mortality. Changes in societal
      structure have fostered an increase in the incidence of diabetes and made the
      traditional hospital visit model less efficient for meeting the care needs of
      these patients. The care models that apply technology, such as telecare or so
      called telehealth, may be useful in working with diabetes patients. The current
      study applied qualitative research methodology through interviews with nine
      diabetes case managers involved in telecare services. To identify the
      participants' acceptance and perceived effectiveness of telecare services,
      content analysis of the interview data was used. The following four major themes
      were identified in the study results: (1) improved case management, (2) setting
      appropriate expectations for care outcome, (3) acknowledging patients' sense of
      losing privacy, and (4) disease prevention and interdisciplinary cooperation. The
      study findings may serve as an indicator of the need for further promotion,
      appraisal, and validation of the telecare services model, to enhance the
      comprehensiveness of diabetes care. 

PMID- 23958967
TI  - Diphenyl diselenide prevents hepatic alterations induced by paraquat in rats.
AB  - This study aimed to investigate the beneficial effect of diphenyl diselenide
      (PhSe)2 on paraquat (PQ) induced alterations in rats liver. Adult male Wistar
      rats received (PhSe)2 at 10 mg kg(-1), by oral administration (p.o.), during five
      consecutive days. Twenty-four hours after the last (PhSe)2 dose, rats received PQ
      at 15 mg kg(-1), in a single intraperitoneally injection (i.p.). Seventy-two
      hours after PQ exposure, animals were sacrificed by decapitation for blood and
      liver samples obtainment. Histological alterations induced by PQ exposure, such
      as inflammatory cells infiltration and edema, were prevented by (PhSe)2
      administration. Moreover, (PhSe)2 prevented hepatic lipid peroxidation (LPO)
      induced by PQ and was effective in reducing the myeloperoxidase (MPO) activity in
      liver, which was enhanced by PQ exposure. (PhSe)2 also was effective in
      protecting against the reduction in ascorbic acid and non-protein thiols (NPSH)
      levels induced by PQ. The inhibition of glutathione S-transferase (GST) activity,
      in rats exposed to PQ, was normalized by (PhSe)2 pre-treatment, whereas the
      inhibition of catalase (CAT) activity was not prevented by (PhSe)2. The serum
      alkaline phosphatase (ALP) inhibition, induced by PQ administration, was also
      prevented by (PhSe)2 pre-treatment. Serum aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) activities were not modified by PQ and/or (PhSe)2
      administration. Therefore, (PhSe)2 pre-treatment was effective in protecting
      against the hepatic alterations induced by PQ in rats. This protective effect can
      involve the antioxidant and anti-inflammatory properties of (PhSe)2.

PMID- 23958968
TI  - The protective effect of grape seed procyanidin extract against cadmium-induced
      renal oxidative damage in mice.
AB  - As an important environmental pollutant, cadmium (Cd) can lead to serious renal
      damage. Grape seed procyanidins extract (GSPE), a biological active component of
      grape seed, has been shown to possess antioxidative effects. Here, we assessed
      the protective effect of GSPE on Cd-induced renal damage using animal experiment.
      After 30 days, the oxidative damage of kidney was evaluated through measurement
      of superoxide dismutase (SOD), glutathione peroxidation (GSH-Px) and
      malondialdehyde (MDA). Since, oxidative stress could lead to apoptosis, the renal
      apoptosis was measured using flow cytometer. Moreover, the expression of
      apoptosis-related protein Bax and Bcl-2 was analyzed by immunohistochemistry and
      Western blot. The results showed that Cd led to the decrease of SOD and GSH-Px
      activities, and the increase of MDA level, induced renal apoptosis. However, the
      coadministration of GSPE attenuated Cd-induced lipid peroxidation, and
      antagonized renal apoptosis, probably associated with the expression of Bax and
      Bcl-2. These data suggested that GSPE has protective effect against renal
      oxidative damage induced by Cd, which provide a potential natural chemopreventive
      agent against Cd-poisoning. 

PMID- 23958969
TI  - Evaluating the inhibitory potential of sulindac against the bleomycin-induced
      pulmonary fibrosis in wistar rats.
AB  - The present study examined the protective effect of sulindac on bleomycin-induced
      lung fibrosis in rats. Animals were divided into saline group, bleomycin group
      (single intra-tracheal instillation of bleomycin) and bleomycin+sulindac (orally
      from day 1 to day 20). Bleomycin administration reduced the body weight, altered
      antioxidant status (such as superoxide dismutase, catalase, glutathione
      peroxidase, glutathione reductase and glutathione) while it increased the lung
      weight, hydroxyproline content, collagen deposition and lipid peroxidation.
      However, simultaneous administration of sulindac improved the body weight,
      antioxidant status and decreased the collagen deposition in lungs. Moreover, the
      levels of inflammatory cytokine tumour necrosis factor-alpha increased in
      bleomycin-induced group, whereas, on treatment with sulindac the levels of tumour
      necrosis factor-alpha were found reduced. Finally, histological evidence also
      supported the ability of sulindac to inhibit bleomycin-induced lung fibrosis. The
      results of the present study indicate that sulindac can be used as an agent
      against bleomycin-induced pulmonary fibrosis. 

PMID- 23958970
TI  - Therapeutic potential of thymoquinone against anti-tuberculosis drugs induced
      liver damage.
AB  - Hepatotoxicity is the most serious adverse effect related to tuberculosis
      treatment which interrupts the successful completion of tuberculosis treatment.
      The purpose of this study was to assess therapeutic effect of thymoquinone (TQ)
      against anti-tuberculosis drugs (ATD) induced liver damage. Rats were treated
      with ATD for 8 weeks (3 days/week) as given for the treatment of TB. This was
      followed by therapy of TQ for 8 weeks (3 days/week). Administration of combined
      ATD induced hepatotoxicity was evident from a significant elevation in the AST,
      ALT, ALP, bilirubin, albumin, cholesterol, urea, uric acid, creatinine, LPO and
      decreased activities of enzymes. These altered variables were significantly
      reversed toward control after treatment with TQ. Histological studies also
      supported biochemical findings. Results of this study strongly indicated
      protective effect of TQ and thus, can be expected as promising protective agent
      in maintenance of normal hepatic function during treatment with ATD. 

PMID- 23958971
TI  - Doxorubicin mediated cardiotoxicity in rats: protective role of felodipine on
      cardiac indices.
AB  - Anthracyclines find vital uses in the treatment of solid tumors and other kind of
      malignancies. A typical side effect observed with few agents of this class is
      dose-dependent cardiotoxicity. Doxorubicin is one such agent which backs the
      generation of free radicals through metabolism of its quinone structure. This
      effect combined with induction of apoptotic and necrotic pathways leads to the
      development of irreversible cardiotoxicity. Reports showing the cardioprotective
      effects of felodipine have been published in the past. We chose to evaluate
      protective effect of felodipine in acute cardiotoxicity in rats induced by single
      dose of doxorubicin. Felodipine was assessed against doxorubicin-induced
      cardiotoxicity and we found that felodipine not only improves cardiac marker
      enzymes (P<0.001 for LDH; P<0.01 for CK-MB) but also prevents damage to
      myocardial tissue (20.61% necrosed area in doxorubicin intoxication; 11.52%
      necrosed area in felodipine treated group). Activation of apoptotic pathways is
      decelerated which is indicated by a significant reduction in myocardial caspase-3
      activity (P<0.05) following felodipine pretreatment. Felodipine pretreatment was
      able to maintain normal cardiac morphology and histoarchitecture. Gravimetric
      analysis revealed beneficial effects following felodipine pretreatment.
      Abnormalities seen in the ECG after doxorubicin treatment were normalized to a
      significant extent (ST interval normalization was significant at P<0.01) in
      felodipine treated rats. In itself, felodipine was not found to have any
      detrimental effects on the myocardium or hemodynamic parameters of rats. Findings
      of the study suggest that pretreatment with felodipine prevents doxorubicin
      induced cardiotoxicity. 

PMID- 23958972
TI  - Cytokine patterns in greenhouse workers occupationally exposed to alpha
      cypermethrin: an observational study.
AB  - The immunotoxicity of the synthetic pyrethroid alpha-cypermethrin (alphaCYP) was
      assessed in 30 occupationally exposed greenhouse workers and 30 non-exposed
      controls by comparing plasma levels of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL
      10, IL-12p70, TNF-alpha, TNF-beta and INF-gamma. Urinary 3-phenoxybenzoic acid
      was used as an exposure biomarker. Exposed workers showed neither clinical signs
      of immunosuppression nor alterations in total leukocytes or leukocyte
      subpopulations, whereas significant differences (p<0.05) were found for IL-12p70
      and highly significant differences (p<0.001) for INF-gamma, IL-2 and IL-8, which
      are involved in antitumor immunity and response to infection. Proinflammatory
      cytokines IL-2, IL-8, IL-12p70 and IFN-gamma play a significant role against
      infection and cancer. We report the first data on the ability of alphaCYP to
      reduce proinflammatory cytokine levels in an exposed healthy human population.
      Findings support the hypothesis that pyrethroid exposure may reduce host defenses
      against infection and cancer, particularly in subjects with impaired immune
      capacity. 

PMID- 23958973
TI  - HI-6 modulates immunization efficacy in a BALB/c mouse model.
AB  - HI-6 is used as an antidote to nerve agents. It can also act as an antagonist to
      acetylcholine receptors (AChRs) including the nicotinic receptor, alpha 7 nAChR
      which is involved in regulating the immune response through macrophages. This
      experiment investigated the efficacy of HI-6 to regulate the immune response.
      Laboratory BALB/c mice received HI-6 and/or keyhole limpet hemocyanin (KLH) as an
      antigen. Antibody production was investigated after either 21 or 65 days when
      either single or repeated dose of antigen was applied. We confirmed that HI-6
      significantly improved vaccination efficacy when KLH was given in a dose of
      1mg/kg. The effect was dose dependent. A combination of HI-6 and KLH produced a
      vaccination of almost the same efficacy as that for Freund's complete adjuvant.
      The findings point at the suitability of HI-6 for improving vaccination efficacy
      at the level of immunity regulation by the nervous system. 

PMID- 23958974
TI  - Green synthesis of silver nanoparticles: an approach to overcome toxicity.
AB  - Nanotechnology, with its advent, has made deep inroads into therapeutics. It has
      revolutionized conventional approaches in drug designing and delivery systems by
      creating a large array of nanoparticles that can pass even through relatively
      impermeable membranes such as blood brain barrier. Like the two sides of a coin,
      nanotechnology too has its own share of disadvantages which in this scenario is
      the toxicology of these nanoparticles. Numerous studies have discussed the
      toxicity of various nanoparticles and the recent advancements done in the field
      of nanotechnology is to make it less toxic. "Green synthesis" of nanoparticles is
      one such approach. The review summarizes the toxicity associated with the
      nanoparticles and the advancement of "green" nanomaterials to resolve the
      toxicity issues. 

PMID- 23958975
TI  - An in vivo insight to the toxicological profile of various organotellurides.
AB  - In this study we have examined the in vivo toxic effects of various
      organochalcogens on hepatic, renal, glycemic and lipid profile. Diorganotellurium
      dichloride phosphonate (C1) at all tested doses did not modify serum alanine
      aminotransferase (ALT) activity in mice. While, 2-butyltellurium furan (C2) and
      dinaphthalene ditelluride (C3) at a dose of 0.75 and 0.125 mmol/kg caused an
      increase in aspartate aminotransferase (AST) and ALT activities. Our data showed
      that C1 caused an increase in urea content at different doses while treatment
      with C2 and C3 did not modify urea content. Treatment with C2 caused a
      significant alteration in serum glucose and fructosamine levels which explains
      the possible toxicity of these compounds. No significant changes were observed
      for cholesterol and triglycerides levels. These results suggest that
      organochalcogen compounds presented liver and renal toxicity and also altered
      glycemic profile which may leads to various clinical complications.

PMID- 23958976
TI  - Evaluation of mysids and sea urchins exposed to saxitoxins.
AB  - Saxitoxins are neurotoxins produced by dinoflagellates and cyanobacteria that
      form toxic blooms in waters. The impact of saxitoxins to the most vulnerable taxa
      and environment are not well understood. The experimental model was based on the
      use of toxic cell extracts containing saxitoxins. This extract was utilized for
      acute and chronic tests with Mysidopsis juniae. Chronic tests were also done with
      Lytechinus variegatus and Arbacia lixula larvae. Acute test with mysids had a
      LC50=2.34 MUg/L. The chronic test with sea urchins showed morphological
      abnormalities resulting in malformation of larval appendices at low
      concentrations of the toxin (EC50=2.96 MUg/L for L. variegatus and 2.06 MUg/L for
      A. lixula). Although saxitoxins are considered neurotoxins, both species of sea
      urchins showed symptoms not related to nerve cells. A. lixula was more sensitive
      than L. variegatus, proving that its sensitivity should be taken in consideration
      to be another option to toxicological tests.

PMID- 23958977
TI  - The future of medical education.

PMID- 23958978
TI  - Keogh identifies failings but outlines achievable aims for improvement.

PMID- 23958980
TI  - Management of liver trauma.

PMID- 23958981
TI  - Is liver transplant for alcohol-related end-stage liver disease appropriate?

PMID- 23958982
TI  - Barrett's oesophagus: diagnosis, surveillance and treatment.

PMID- 23958983
TI  - Applications of Laplace's law in clinical medicine: a radiological pictorial
      review.

PMID- 23958984
TI  - The NHS breast screening programme.

PMID- 23958985
TI  - Cauda equina syndrome: a clinical review for the frontline clinician.

PMID- 23958986
TI  - Enhancing patient safety with an electronic results checking system in a large
      HIV outpatient service.
AB  - OBJECTIVE: To establish whether an automated electronic tracker system for
      reporting blood results would expedite clinician review of abnormal results in
      HIV-positive outpatients and to pilot the use of this system in routine clinical
      practice. SETTING: An outpatient service in central London providing specialist
      HIV-related care to 3900 HIV positive patients. DESIGN: A comparison of the time
      taken from sampling to identification and clinician review of abnormal blood
      results for biochemical tests between the original paper-based checking system
      and an automated electronic system during a 3-week pilot. RESULTS: Of 513
      patients undergoing one or more blood tests, 296 (57%) had one or more
      biochemical abnormalities identified by electronic checking system. Out of 371
      biochemical abnormalities, 307 (82.7%) were identified simultaneously by the
      paper-based system. Of the 307, 33 (10.7%) were classified as urgent, 130 (42.3%)
      as non-urgent and 144 (46.9%) as not clinically significant. The median interval
      between sampling and receipt of results was 1 (interquartile range 1-2) vs 4 days
      ( interquartile range 3-5), P <0.0001; clinician review 3 (interquartile range 1
      4) vs 3 days (interquartile range 3-6), P<0.037; and review of non-urgent
      abnormalities by the regular clinician 2 (interquartile range 1-4) vs 10 days (
      interquartile range 9-12), P=0.136, for electronic and paper-based systems
      respectively. Seven (11%) of the missing paper-based system results were
      classified as urgent. The electronic system missed three abnormalities as a
      result of a software processing error which was subsequently corrected.
      CONCLUSIONS: The electronic tracker system allows faster identification of
      biochemical abnormalities and allowed faster review of these results by
      clinicians. The pilot study allowed for a software error to be identified and
      corrected before full implementation. The system has since integrated
      successfully into routine clinical practice.

PMID- 23958988
TI  - Norwegian scabies.

PMID- 23958987
TI  - IgG4 disease: a revised diagnosis of sarcoidosis after 36 years of treatment.

PMID- 23958989
TI  - A rare case of isolated cutaneous metastases of colonic adenocarcinoma.

PMID- 23958990
TI  - Intraperitoneal bladder rupture.

PMID- 23958991
TI  - Claude Bernard: a founder of experimental medicine.

PMID- 23958992
TI  - A caveat for thrombolytic treatment of stroke?

PMID- 23958993
TI  - Pension liberation is not the answer to early retirement.

PMID- 23958995
TI  - What is the value of the pulmonary artery catheter in critical care and
      anaesthesia?

PMID- 23958996
TI  - Experimental simulation of quantum tunneling in small systems.
AB  - It is well known that quantum computers are superior to classical computers in
      efficiently simulating quantum systems. Here we report the first experimental
      simulation of quantum tunneling through potential barriers, a widespread
      phenomenon of a unique quantum nature, via NMR techniques. Our experiment is
      based on a digital particle simulation algorithm and requires very few spin-1/2
      nuclei without the need of ancillary qubits. The occurrence of quantum tunneling
      through a barrier, together with the oscillation of the state in potential wells,
      are clearly observed through the experimental results. This experiment has
      clearly demonstrated the possibility to observe and study profound physical
      phenomena within even the reach of small quantum computers. 

PMID- 23958997
TI  - Redox balance in the aged endothelium.
AB  - The endothelium is located in a strategic anatomical position within the blood
      vessel wall and thus constitutes a barrier between the blood and all tissues. The
      integrity of the endothelial cells, which line the entire circulatory system like
      wallpaper, is essential to prevent the onset of cardiovascular disorders. Aging
      is one of the major risk factors for the development of heart and vascular
      diseases. However, over the past years it has become clear that the functional
      capacity of endothelial cells declines with age and that physiological aging
      occurs independently of pathological changes. One important mechanism
      contributing to the onset of the aging. process is the disturbance of the
      cellular redox homeostasis. Two key molecules involved in maintaining the
      delicate balance between oxidative and antioxidative systems are NADPH oxidase 4,
      an enzyme whose sole function is to produce reactive oxygen species and the
      oxidoreductase thioredoxin-1, which reduces oxidized proteins. Therefore, this
      review will focus on the role of these two proteins in cardiovascular aging.

PMID- 23958998
TI  - [Residential mobility in old age. Age-appropriate housing as a primary preventive
      strategy].
AB  - BACKGROUND: Unfavorable living conditions in old age have negative physical,
      psychological and social implications and increase the risk of
      institutionalization. The aim of this study is to examine older adults' readiness
      to relocate to age-appropriate housing versus the wish to stay where they are.
      METHODS: A total of 103 older men and women were questioned prospectively, face
      to-face, regarding their readiness to relocate. In addition to assessing several
      established predictors of residential mobility, data on objective living
      situations were collected. The data were subjected to bi- and multivariate
      analysis. RESULTS: At 70.9%, the proportion of respondents who are not willing to
      move (stayers) far exceeds the proportion of those who are (movers, 29.1%). Older
      respondents are more satisfied with their living situation and less likely to
      move. This study provides empirical evidence for the "satisfaction paradox" with
      respect to living conditions and for the importance of the subjective standard of
      living for quality of life in old age. CONCLUSION: Modern housing counseling
      should more strongly reflect the variety of needs, requirements and living
      situations of older people today than it has done in the past. It is therefore
      recommended that the currently dominating paradigm of "aging in place" be
      critically re-evaluated.

PMID- 23958999
TI  - Nitric oxide regulates AKT phosphorylation and nuclear translocation in cultured
      retinal cells.
AB  - Previous studies have shown that nitric oxide (NO) inhibits apoptosis of retinal
      neurons in culture through the canonical cyclic GMP/protein kinase G (PKG)
      dependent pathway, but also involving multiple kinase pathways, such as
      phosphatidylinositol 3' kinase (PI3k) and AKT. NO and AKT exhibit survival
      promoting properties and display important roles in both CNS development and
      plasticity. The purpose of this study was to evaluate the effects of exogenous
      NO, derived from the NO donor S-nitroso-N-acetylpenicillamin (SNAP), or
      endogenous NO, produced from l-arginine, on AKT phosphorylation in cultured chick
      retinal neurons. Our results demonstrate that SNAP or l-arginine enhances AKT
      phosphorylation on both serine-473 and threonine-308 residues in a concentration
      and time-dependent manner. This effect was mediated by the activation of soluble
      guanylyl cyclase and PKG, since it was blocked by the respective enzyme
      inhibitors ODQ or LY83583 and KT5823, as well as by transduction with shRNA
      lentiviruses coding PKGII shRNA, and mimicked by the respective enzyme activators
      YC-1 and 8-Bromo cyclic GMP, and also by the cyclic GMP phosphodiesterase
      inhibitor zaprinast. In addition, LY294002 or wortmannin suppressed the SNAP
      effect, indicating the involvement of phosphoinositide 3' kinase. Moreover, the
      mTOR inhibitor KU0063794 blocked SNAP-induced AKT phosphorylation at both
      residues, suggesting the participation of the mTORC2 complex in the process.
      Glutamate and NMDA also promoted AKT phosphorylation and a nitric oxide synthase
      inhibitor abrogated these effects, revealing a mechanism involving the activation
      of NMDA receptors and NO production. We have also found that SNAP and l-arginine
      induced AKT translocation into the nucleus of retinal neurons as well as other
      neuronal cell lines. SNAP also protects retinal cells from death induced by
      hydrogen peroxide and this effect was blocked by the phosphoinositide 3' kinase
      inhibitor LY294002. We therefore conclude that NO produced from endogenous or
      exogenous sources promotes AKT activation and its shuttling to the nucleus,
      probably participating in neuronal survival pathways important during CNS
      development. 

PMID- 23959000
TI  - Confirmation of the coexistence of two tautomers of 2-mercaptothiazoline on the
      Ge(100) surface.
AB  - We confirmed the coverage dependent variation of tautomers of 2
      mercaptothiazoline (the thiolate and thione forms) adsorbed on the Ge(100)
      surface under UHV conditions by using HRXPS measurements in conjunction with the
      DFT calculation method, which was studied before only in aqueous systems. The C
      1s, S 2p, and N 1s core-level spectra obtained using HRXPS revealed the
      simultaneous presence of two distinct adsorption structures in different
      proportions at both low (0.15 ML) and high (0.65 ML) coverages. Moreover, we
      modelled the adsorption structures and geometric configurations of the bond
      states of 2-mercaptothiazoline on the Ge(100) surface by using the DFT
      calculation method, and found that the S dative bonded structure is the most
      stable adsorption structure for the thione form of 2-mercaptothiazoline and that
      the S-H dissociated-N dative bonded structure is the most stable adsorption
      structure for the thiolate form. 

PMID- 23959001
TI  - The satiety signal oleoylethanolamide stimulates oxytocin neurosecretion from rat
      hypothalamic neurons.
AB  - The anandamide monounsaturated analogue oleoylethanolamide (OEA) acts as satiety
      signal released from enterocytes upon the ingestion of dietary fats to prolong
      the interval to the next meal. This effect, which requires intact vagal fibers
      and intestinal PPAR-alpha receptors, is coupled to the increase of c-fos and
      oxytocin mRNA expression in neurons of the paraventricular nucleus (PVN) and is
      prevented by the intracerebroventricular administration of a selective oxytocin
      antagonist, thus suggesting a necessary role of oxytocinergic neurotransmission
      in the pro-satiety effect of OEA. By brain microdialysis and
      immunohistochemistry, in this study we demonstrate that OEA treatment can
      stimulate oxytocin neurosecretion from the PVN and enhance oxytocin expression at
      both axonal and somatodendritic levels of hypothalamic neurons. Such effects,
      which are maximum 2h after OEA administration, support the hypothesis that the
      satiety-inducing action of OEA is mediated by the activation of oxytocin
      hypothalamic neurons. 

PMID- 23959002
TI  - Profile of HIV-infected patients receiving second-line antiretroviral therapy in
      a resource-limited setting in Nigeria.
AB  - BACKGROUND: Second-line antiretroviral therapy (ART) accounts for less than 5% of
      total ART in resource-limited settings. We described the baseline
      characteristics, reasons for switch and treatment outcomes of Nigerian patients
      receiving second-line ART. METHODS: In this retrospective cohort study we
      recorded the baseline characteristics of HIV-infected adults whose treatment
      regimen was switched from a non-nucleoside reverse transcriptase inhibitor, a
      first-line agent, to a protease inhibitor-based second-line regimen. The duration
      of follow-up was 12 months. RESULTS: Of 4229 patients who started first-line
      therapy, 186 (4.4%) were switched to second-line therapy after a mean duration of
      16.6 +/- 7.6 months. Their mean age was 41.8 +/- 9.6 years and 59.1% were women.
      The median (range) viral load and CD4 cell counts at switch were 4.7 (4.1-6.3)
      log10 copies/ml and 71 (6-610) cells/ul, respectively. The predominant reason for
      switch was virological failure (79.0%). Only 55.4% and 36.6% of patients had CD4
      cell count and viral load at 12 months. About 82%, 79% and 82% of patients with
      available data achieved virological suppression at 3 months, 6 months and 12
      months respectively (p = 0.81). The proportion of patients who achieved >=50%
      rise in CD4 cell count increased from 55.8% at 3 months to 78.6% at 12 months (p
      = 0.0002). CONCLUSION: The rate of switch to second-line therapy was low but
      there were good treatment outcomes among patients with available data. Attrition
      rate was high. Regular viral load monitoring, improved availability/affordability
      of second-line regimens and retention in care should become priorities in
      resource-limited settings.

PMID- 23959003
TI  - Seroprevalence of hepatitis A virus infection among schoolchildren and
      adolescents in Kaduna, Nigeria.
AB  - BACKGROUND: Hepatitis A is an infectious viral disease, caused by hepatitis A
      virus (HAV), endemic in many developing countries. A recent review of the global
      prevalence of HAV infection and susceptibility by the WHO had few data on the
      seroprevalence of HAV in Nigeria. This study was designed to determine the
      seroprevalence of HAV among schoolchildren and adolescents in Kaduna State and to
      identify factors associated with seropositivity. METHODS: Questionnaires were
      administered to 403 participants aged 2-19 years, and blood samples were
      collected during April-July 2009 and screened for anti-HAV IgG using an anti-HAV
      IgG enzyme immunoassay kit. chi(2) and Fisher's exact tests were used to identify
      variables associated with the presence of anti-HAV IgG. RESULTS: The mean +/- SD
      age of the study population was 11.7 +/- 3.2 years. Of the 403 serum samples, 29
      were positive for HAV, giving an overall seroprevalence of 7.2% (95% CI 4.9
      10.2%) among the study population. Seropositivity with respect to age ranged from
      4.6% (10/218; 95% CI 2.2-8.3%) in the 11-15 years age group to 30% (3/10; 95% CI
      6.7-65.3%) in the <=5 years age group. Anti-HAV seropositivity was associated
      with sewage disposal methods and parents' educational level (p < 0.05).
      CONCLUSION: This study shows that the majority of the study population lacked
      natural immunity (anti-HAV IgG). This low HAV exposure may be attributed to
      improvements in sanitary conditions and socioeconomic status. Further research
      involving an older population in different parts of the country is required to
      determine the current epidemiological pattern of HAV.

PMID- 23959004
TI  - Highly dispersed palladium nanoparticles anchored on UiO-66(NH2) metal-organic
      framework as a reusable and dual functional visible-light-driven photocatalyst.
AB  - Proper design and preparation of high-performance and stable dual functional
      photocatalytic materials remains a significant objective of research. In this
      work, highly dispersed Pd nanoparticles of about 3-6 nm in diameter are
      immobilized in the metal-organic framework (MOF) UiO-66(NH2) via a facile one-pot
      hydrothermal method. The resulting Pd@UiO-66(NH2) nanocomposite exhibits an
      excellent reusable and higher visible light photocatalytic activity for reducing
      Cr(vi) compared with UiO-66(NH2) owing to the high dispersion of Pd nanoparticles
      and their close contact with the matrix, which lead to the enhanced light
      harvesting and more efficient separation of photogenerated electron-hole pairs.
      More significantly, the Pd@UiO-66(NH2) could be used for simultaneous
      photocatalytic degradation of organic pollutants, like methyl orange (MO) and
      methylene blue (MB), and reduction of Cr(vi) with even further enhanced activity
      in the binary system, which could be attributed to the synergetic effect between
      photocatalytic oxidation and reduction by individually consuming photogenerated
      holes and electrons. This work represents the first example of using the MOFs
      based materials as dual functional photocatalyst to remove different categories
      of pollutants simultaneously. Our finding not only proves great potential for the
      design and application of MOFs-based materials but also might bring light to new
      opportunities in the development of new high-performance photocatalysts.

PMID- 23959005
TI  - Intramolecular Paterno-Buchi reaction of atropisomeric alpha-oxoamides in
      solution and in the solid-state.
AB  - Atropisomeric alpha-oxoamides were synthesized and employed for intramolecular
      Paterno-Buchi reaction leading to very high enantio- and diastereoselectivity in
      the bicyclic oxetane photoproduct. A reversal of product selectivity was observed
      in solution and in the solid-state. 

PMID- 23959006
TI  - Direct asymmetric syntheses of chiral aldehydes and ketones via N-acyl chiral
      auxiliary derivatives including chiral Weinreb amide equivalents.
AB  - This article covers N-acyl chiral auxiliary-based approaches to the asymmetric
      synthesis of enantiopure aldehydes and ketones. The use of diastereoisomerically
      pure N-acyl derivatives of chiral auxiliaries (including chiral Weinreb amide
      equivalents) and their conversion to the corresponding enantiopure aldehydes and
      ketones in a single synthetic operation by treatment with a hydride reducing
      agent or an organometallic reagent, respectively, are highlighted. 

PMID- 23959007
TI  - Monte Carlo modelling of large scale NORM sources using MCNP.
AB  - The representative Monte Carlo modelling of large scale planar sources (for
      comparison to external environmental radiation fields) is undertaken using
      substantial diameter and thin profile planar cylindrical sources. The relative
      impact of source extent, soil thickness and sky-shine are investigated to guide
      decisions relating to representative geometries. In addition, the impact of
      source to detector distance on the nature of the detector response, for a range
      of source sizes, has been investigated. These investigations, using an MCNP based
      model, indicate a soil cylinder of greater than 20 m diameter and of no less than
      50 cm depth/height, combined with a 20 m deep sky section above the soil
      cylinder, are needed to representatively model the semi-infinite plane of
      uniformly distributed NORM sources. Initial investigation of the effect of
      detector placement indicate that smaller source sizes may be used to achieve a
      representative response at shorter source to detector distances.

PMID- 23959008
TI  - Foundational errors in the Neutral and Nearly-Neutral theories of evolution in
      relation to the Synthetic Theory: is a new evolutionary paradigm necessary?
AB  - The Neutral Theory of Evolution (NTE) proposes mutation and random genetic drift
      as the most important evolutionary factors. The most conspicuous feature of
      evolution is the genomic stability during paleontological eras and lack of
      variation among taxa; 98% or more of nucleotide sites are monomorphic within a
      species. NTE explains this homology by random fixation of neutral bases and
      negative selection (purifying selection) that does not contribute either to
      evolution or polymorphisms. Purifying selection is insufficient to account for
      this evolutionary feature and the Nearly-Neutral Theory of Evolution (N-NTE)
      included negative selection with coefficients as low as mutation rate. These NTE
      and N-NTE propositions are thermodynamically (tendency to random distributions,
      second law), biotically (recurrent mutation), logically and mathematically
      (resilient equilibria instead of fixation by drift) untenable. Recurrent forward
      and backward mutation and random fluctuations of base frequencies alone in a site
      make life organization and fixations impossible. Drift is not a directional
      evolutionary factor, but a directional tendency of matter-energy processes
      (second law) which threatens the biotic organization. Drift cannot drive
      evolution. In a site, the mutation rates among bases and selection coefficients
      determine the resilient equilibrium frequency of bases that genetic drift cannot
      change. The expected neutral random interaction among nucleotides is zero;
      however, huge interactions and periodicities were found between bases of
      dinucleotides separated by 1, 2... and more than 1,000 sites. Every base is co
      adapted with the whole genome. Neutralists found that neutral evolution is
      independent of population size (N); thus neutral evolution should be independent
      of drift, because drift effect is dependent upon N. Also, chromosome size and
      shape as well as protein size are far from random. 

PMID- 23959009
TI  - Increasing the rate of drying reduces metabolic imbalance, lipid peroxidation and
      critical water content in radicles of garden pea (Pisum sativum L.).
AB  - Orthodox seeds become desiccation-sensitive as they undergo germination. As a
      result, germinating seeds serve as a model to study desiccation sensitivity in
      plant tissues. The effects of the rate of drying on the viability, respiratory
      metabolism and free radical processes were thus studied during dehydration and
      wet storage of radicles of Pisum sativum. For both drying regimes desiccation
      could be described by exponential and inverse modified functions. Viability, as
      assessed by germination capacity and tetrazolium staining, remained at 100%
      during rapid (< 24 h) desiccation. However, it declined sharply at c. 0.26 g g1
      dm following slow (c. 5 days) drying. Increasing the rate of dehydration thus
      lowered the critical water content for survival. Rapid desiccation was also
      associated with higher activities and levels of malate dehydrogenase and the
      oxidized form of nicotinamide adenine dinucleotide. It was also accompanied by
      lower hydroperoxide levels and membrane damage. In addition, the activitiy of
      glutathione reductase was greater during rapid drying. Ageing may have
      contributed to increased damage during slow dehydration, since viability declined
      even in wet storage after two weeks. The results presented are consistent with
      rapid desiccation reducing the accumulation of damage resulting from desiccation
      induced aqueous-based deleterious reactions. In addition, they show that radicles
      are a useful model to study desiccation sensitivity in plant tissues. 

PMID- 23959010
TI  - Effectiveness of zinc in modulating perinatal effects of arsenic on the
      teratological effects in mice offspring.
AB  - Exposure to arsenic via drinking water is considered as a worldwide problem.
      Studies have shown that arsenic exposure during pregnancy affects embryogenesis
      and offspring development in rats and mice. Zinc as a micronutrient regulates
      many physiological functions, including an antioxidative role under various toxic
      conditions. However, studies on the perinatal protective effect of zinc on
      offspring need further attention. The present study was designed to evaluate the
      potential protective role of zinc in mitigating the adverse effects in the
      offspring of arsenic exposure during pregnancy. The arsenic (40mg/kg body weight)
      and zinc (4% w/v) doses formed the only drinking fluid source for the
      experimental groups of dams during the perinatal period of the experiment. The
      early development of sensory motor coordination reflexes together with
      morphological development in the male pups was measured during the weaning
      period. In adolescence, the offspring were tested for their motor behavior. The
      enzyme gamma-glutamyl transferase (gamma-GT) and the oxidative stress indices
      like reduced glutathione (GSH) and lipid peroxidation (TBARS) were also estimated
      in the serum of the young adult male mice. Perinatal arsenic exposure caused
      depletion in body weight gain, delay in morphological development and retardation
      in the development of all sensory motor reflexes of the pups. In young adults,
      significant decrease in motor behavior with significant decrease in GSH level in
      the serum was observed. On the other hand, gamma-GT and TBARS were significantly
      increased in the serum due to arsenic treatment. However, animals exposed to
      arsenic in the presence of zinc showed a remarkable ameliorating effect of zinc
      on all observed teratological and biochemical arsenic toxicity in male offspring.
      It was observed that zinc has an antioxidative role in the perinatal toxicity of
      arsenic. It is concluded from the present study that zinc consumed during the
      perinatal period of pregnancy can ameliorate the possible toxicities of arsenic
      exposure in the offspring by acting as an ameliorative supplement. 

PMID- 23959011
TI  - Disruption of reproductive development in male rat offspring following
      gestational and lactational exposure to di-(2-ethylhexyl) phthalate and
      genistein.
AB  - Studies of developmental effects of mixtures of endocrine disrupters on the male
      reproductive system are of great concern. In this study, the reproductive effects
      of the co-administration of di-2-(ethylhexyl) phthalate (DEHP) and genistein
      (GEN) during pregnancy and lactation were studied in male rat offspring. Pregnant
      Sprague-Dawley rats were gavaged from gestation day 3 to postnatal day 21 with
      vehicle control, DEHP 250 mg/kg body weight (bwyday, GEN 50 mg/kg bwday, GEN 400
      mg/kg bwday, and two combinations of the two compounds (DEHP 250 mg/kg bwday +
      GEN 50 mg/kg bwday, DEHP 250 mg/kg bwday + GEN 400 mg/kg bwday). The outcomes
      studied were general morphometry (weight, AGD), testicular histology,
      testosterone levels, and expression at the mRNA level of genes involved in
      steroidogenesis. Organ coefficient, AGD / body weight1/3 ?, serum testosterone
      concentration and genes involved in steroidogenic pathway expression when exposed
      to DEHP (250mg/kg bwday), GEN(50mg/kg bwday) or GEN(400mg/kg bwday) alone were
      not significantly different from the control group. When exposed to (DEHP
      250mg/kg bwday +GEN 50mg/kg bwday) together during pregnancy and lactation, serum
      testosterone concentration, epididymis coefficient and Cypal17a1,Scarb1 m RNA
      expression significantly decreased compared to the control and GEN(50mg/kg
      bwday). When exposed to (DEHP 250mg/kg bwday +GEN 400mg/kg bwday) together during
      pregnancy and lactation, AGD / body weight1/3 ?, serum testosterone
      concentration, testis and epididymis coefficient and Star, Cypal17a1 mRNA
      expression appeared significantly decreased compared to the control and DEHP/GEN
      single exposure, together with developmental impairment of seminiferous tubules
      and seminiferous epithelium. Overall, co-administration of DEHP and GEN during
      gestation and lactation seem to acts in a cumulative manner to induce the most
      significant alterations in the neonate, especially with GEN at high dose,
      although the effect of the DEHP-GEN mixture on adult offspring should be observed
      further. 

PMID- 23959012
TI  - Electrolyzed-reduced water increases resistance to oxidative stress, fertility,
      and lifespan via insulin/IGF-1-like signal in C. elegans.
AB  - Electrolyzed-reduced water (ERW) scavenges reactive oxygen species and is a
      powerful anti-oxidant. A positive correlation between oxidative stress and aging
      has been proved in many model organisms. In Caenorhabditis elegans, many long
      lived mutants showed reduced fertility as a trade off against longevity
      phenotype. We aimed to study the effect of ERW on oxidative stress, fertility and
      lifespan of C. elegans. We also investigated the genetic pathway involved in the
      effect of ERW on resistance to oxidative stress and lifespan. We compared
      lifespan and fertility of worms in media prepared with distilled water and ERW.
      ERW significantly extended lifespan and increased the number of progeny produced.
      Then the effect of ERW on resistance to oxidative stress and lifespan of long
      lived mutants was determined. ERW increased resistance to oxidative stress and
      lifespan of eat-2, a genetic model of dietary restriction, but had no effect on
      those of age-1, which is involved in insulin/insulin-like growth factor (IGF)-1
      like signal. In addition, knockdown of daf-16, the downstream mediator of
      insulin/IGF-1-like signal, completely prevented the effect of ERW on lifespan.
      These findings suggest that ERW can extend lifespan without accompanying reduced
      fertility and modulate resistance to oxidative stress and lifespan via
      insulin/IGF-1-like signal in C. elegans. 

PMID- 23959013
TI  - Anti-lipase and antioxidant properties of 30 medicinal plants used in Oaxaca,
      Mexico.
AB  - We report the results of in vitro anti-lipase and antioxidant assays using crude
      ethanolic extracts from 30 plants grown in Oaxaca, Mexico. Anti-lipase tests were
      performed by using porcine pancreatic lipase (PPL) [EC 3.1.1.3] from
      Affymetrix/USB. The extracts of Solanum erianthum, Salvia microphylla,
      Brungmansia suaveolens and Cuphea aequipetala showed up to 60% PPL inhibition.
      The effect of these extracts on the kinetic parameters of PPL (Km= 0.36 mM, and
      Vmax=0.085 mM min -1) revealed that the alcoholic preparations of S. erianthum
      and C. aequipetala engendered a non-competitive inhibition (Vmax=0.055 mM min -1;
      Vmax= 0.053 mM min -1), whereas those of S. microphylla and B. suaveolens
      produced a mixed inhibition (Km= 0.567 mM, Vmax=0.051 mM min _1; Km=0.643 mM,
      Vmax= 0.042 mM min 1). In addition to these findings, seven extracts from
      different plants were able to inhibit PPL in the range of 30-50%. Antioxidant
      tests against 2,2-Diphenyl-1-picryl hydrazyl (DPPH) confirmed that Arctostaphylos
      pungens, Gnaphalium roseum, Crotalaria pumila, Cuphea aequipetala, Rhus
      chondroloma, and Satureja laevigata possess relevant antioxidant activity
      (IC(5)0=50-80 MUg mL1). The general composition of the most effective ethanolic
      extracts was obtained in order to confirm their known chemistry reported by
      previous works. Comprehensive chemical analysis of the ethanolic extracts and
      their poisoning effects suggests that S. microphylla, C. aequipetala and A.
      pungens could be considered as the best sources with both desired properties. 

PMID- 23959014
TI  - DNA Repair Genes XRCC1, XRCC3, XPD, and OGG1 Polymorphisms among the Central
      Region Population of Saudi Arabia.
AB  - DNA repair is one of the central defense mechanisms against mutagenic exposures.
      Inherited SNPs of DNA repair genes may contribute to variations in DNA repair
      capacity and susceptibility to cancer. Due to the presence of these variants,
      inter-individual and ethnic differences in DNA repair capacity have been
      established in various populations. Saudi Arabia harbors enormous genetic and
      cultural diversity. In the present study we aimed to determine the genotype and
      allele frequencies of XRCC1 Arg399Gln (rs25487), XRCC3 Thr241Met (rs861539), XPD
      Lys751Gln (rs13181), and OGG1 Ser326Cys (rs1052133) gene polymorphisms in 386
      healthy individuals residing in the central region of Saudi Arabia and compare
      them with HapMap and other populations. The genotype and allele frequencies of
      the four DNA repair gene loci in central Saudi population showed a distinctive
      pattern. Furthermore, comparison of polymorphisms in these genes with other
      populations also showed a unique pattern for the central Saudi population. To the
      best of our knowledge, this is the first report that deals with these DNA repair
      gene polymorphisms among the central Saudi population. 

PMID- 23959015
TI  - mRNA expression profile of selected oxygen sensing genes in the lung during
      recovery from chronic hypoxia.
AB  - This study analyzed the time dependence decay of the mRNA of selected genes
      important for the hypoxia response. The genes chosen were the two isoforms of
      hypoxia-inducible factors, the three isoforms of the prolyl hydroxylase domain
      protein, the vascular endothelial growth factor and endothelial nitric oxide
      synthase. mRNA and proteins were extracted from lungs obtained from control,
      hypoxic and 15 minutes normoxic recovered rats and analyzed by Real-time RT-PCR
      or by the Western Blot technique. Results indicated that in normoxia isoform 2a
      was the more represented hypoxia-inducible factor mRNA, and among the prolyl
      hydroxylase domain transcripts, isoform 3 was the least abundant. Moreover, in
      chronic hypoxia only hypoxia-inducible factor 1alpha and prolyl hydroxylase
      domain protein 3 increased significantly, while after 15 minutes of recovery all
      the mRNAs tested were decreased except endothelial nitric oxide synthase mRNA. In
      terms of proteins, hypoxia-inducible 1alpha was the isoform more significant in
      the nucleus, while 2a predominated in the cytosol. While the former was steady
      even after a brief recovery from hypoxia, the latter underwent a strong
      degradation. In conclusion we showed the relevance of the decay in the mRNA and
      protein levels upon re-oxygenation in normoxia. We believe that this has to be
      considered in research studies dealing with recovery from hypoxia. 

PMID- 23959016
TI  - Phenolic profiles of nectar and honey of Quillaja saponaria Mol. (Quillajaceae)
      as potential chemical markers.
AB  - Quillaja saponaria Mol. (Quillajaceae) is one of the most important melliferous
      species in Chile, mainly as a source of monofloral honey. Honey made by A.
      mellifera presents biological activity against pathogens and antioxidant capacity
      associated with the presence of phenolic compounds deriving from the nectar, as a
      result of bee honey foraging. The aim of this study was to identify and quantify
      the phenolic compounds from the floral nectar of Q. saponaria and the honey made
      in apiaries in the central zone, and compare the composition of the
      chromatographic profiles of nectar and honey to known phenolic compounds. The
      results obtained by HPLC-DAD (high-performance liquid chromatography with diode
      array detection) showed a similar profile of phenolic compounds, in which gallic
      acid, myricetin, rutin, quercetin and naringenin were identified. The phenolic
      compounds detected could be used as a reference for future studies for
      determining potential chemical markers of this honey, complementing the present
      identification of honeys by determining their botanical origin. The
      identification of bioindicators of the floral origins for honey of this species
      could provide added value to honey commercialization by certifying the botanical
      origin of their chemical features and biological attributes. 

PMID- 23959017
TI  - Effects of Dangguibuxue Tang, a Chinese herbal medicine, on growth performance
      and immune responses in broiler chicks.
AB  - The effects of Dangguibuxue Tang (DBT) on growth performance and immunity
      response in immunosuppressed broiler chicks were investigated in this study. 240
      one-d-old broiler chicks (DaHeng S01) were randomly divided into 4 groups, 2.0%
      DBT-treatment (A), 0.5% DBT-treatment (B), cyclophosphamide-control (C), and
      control group (D). From 4 d to 7 d of age, chicks in group A, B and C were given
      cyclophosphamide (CY) at a dosage of 100mg/kg body weight (BW) daily by
      intraperitoneal injection to induce immunosuppression. Chicks in group D were
      given an equal volume of physiological saline daily by intraperitoneal injection
      and considered normal chicks. Groups A and B were supplemented with 2.0% or 0.5%
      of DBT in the drinking water from 8 d to 42 d of age. Groups C and D did not
      receive any additional medication. The results revealed that chicks from group B
      had lower feed:gain rate (FGR), lower total mortality, higher immunity organ
      indexes, higher levels of Newcastle disease (ND) antibody and infectious bursal
      disease (IBD) antibody, higher interleukin-2 and interleukin-6 levels, and
      greater lymphocyte proliferative responses to concanavalin A (ConA) during the
      experiment than those from group C. However, no significant difference in the
      immunity status in the two levels of DBT-treatment was observed. These results
      indicate that supplementation of 0.5% of DBT can improve both cellular immunity
      and humoral immunity in immunosuppressed broiler chicks. 

PMID- 23959018
TI  - Protective effects of lycopene on oxidative stress, proliferation and autophagy
      in iron supplementation rats.
AB  - Lycopene is common in diet and known for its antioxidant activities. However, the
      impact of lycopene on iron metabolism is poorly investigated. In this study, we
      hypothesize that lycopene can prevent iron-mediated oxidative stress,
      proliferation and autophagy in liver and use a rat model of nutritional iron
      supplementation to confirm its intervention in these defence mechanisms. We found
      that iron supplementation induced cell proliferation predominantly in non
      parenchymal cells compared with hepatocytes, but not apoptosis. In addition, iron
      was accumulated within the hepatic lysosomes where it triggered autophagy as
      evidenced by the formation of autophagic vesicles detected by LC3-B staining.
      Iron supplementation also induced morphologic alterations of the mitochondrial
      membranes probably due to increased lipid peroxidation as indicated by elevated
      iron and malondialdehyde concentrations in serum and tissues. Lycopene reduced
      iron-catalyzed lipid peroxidation by decreasing the malondialdehyde level in the
      liver and colon and enhancing the total superoxide dismutase activities in serum
      and tissues. The result suggest that lycopene prevents iron-induced oxidative
      stress, proliferation and autophagy at both biochemical and histological levels
      due to its potent free radical scavenging and antioxidant properties. 

PMID- 23959019
TI  - Analysis of mRNA expression profiles of carotenogenesis and astaxanthin
      production of Haematococcus pluvialis under exogenous 2, 4-epibrassinolide (EBR).
AB  - The fresh-water green unicellular alga Haematococcus pluvialis is known to
      accumulate astaxanthin under stress conditions. In the present study,
      transcriptional expression of eight genes involved in astaxanthin biosynthesis
      exposed to EBR (25 and 50 mg/L) was analyzed using qRT-PCR. The results
      demonstrated that both 25 and 50 mg/L EBR could increase astaxanthin productivity
      and the eight carotenogenic genes were up-regulated by EBR with different
      expression profiles. Moreover, EBR25 induction had a greater influence on the
      transcriptional expression of ipi-1, ipi-2, crtR-B, lyc and crtO (> 5- fold up
      regulation) than on psy, pds, bkt; EBR50 treatment had a greater effect on the
      transcriptional expression of ipi-2, pds, lyc, crtR-B, bkt and crtO than on ipi-1
      and psy. Furthermore, astaxanthin biosynthesis under EBR was up-regulated mainly
      by ipi1? and psy at the post-transcriptional level, pds, lyc, crtR-B, bkt and
      crtO at the transcriptional level and ipi-2 at both levels. 

PMID- 23959020
TI  - Relationship between severity of adult community-acquired pneumonia and
      impairment of the antioxidant defense system.
AB  - Oxidant/antioxidant imbalance has been reported in some infectious diseases,
      including community-acquired pneumonia (CAP). The aim was to assess the
      antioxidant status in adults with CAP and its relationship with clinical severity
      at admission. Fifty-nine patients with CAP were enrolled and categorized at
      admission by the FINE score, from July 2010 to October 2012. In the same period
      61 controls were enrolled. Plasma samples were obtained at admission for
      determination of the ferric reducing ability of plasma (FRAP) and lipid
      peroxidation (8-isoprostane). Erythrocyte reduced (GSH)/oxidized (GSSG)
      glutathione, malondialdehyde (MDA) and antioxidant enzyme activity were assessed.
      Antioxidant status in adults with CAP represented by FRAP and the GSH/GSSG ratio
      were 16.8% (p=0.03) and 39.7% (p=0.04) lower than control values, respectively.
      In addition, FRAP values showed a positive correlation with GSH/GSSG ratio
      (r=0.852; p<0.02; n=59). The CAP group showed greater lipid peroxidation in both
      plasma and erythrocytes. The FINE score correlated negatively with FRAP (r= 
      0.718; p<0.05; n=59) and positively with MDA and F2 isoprostane levels (r=0.673;
      p<0.05; n=59; r=0.892; p<0.01; n=59, respectively). Antioxidant status
      alterations correlated with clinical severity. The FRAP assay and lipid
      peroxidation biomarkers may provide a useful parameter for estimating the
      severity and the clinical outcome of patients with CAP. 

PMID- 23959021
TI  - Aerobic Ru-catalyzed direct C2-olefination of N-heteroarenes with alkenes
      directed by a removable N-dimethylcarbamoyl group.
AB  - A highly efficient and selective Ru-catalyzed direct C2-olefination of indoles,
      pyrroles, and carbazoles assisted by a removable N-dimethylcarbamoyl group has
      been developed by using O2 as the terminal oxidant. Both electron-deficient and
      unactivated alkenes are applicable to the protocol. 

PMID- 23959022
TI  - The periconceptional period, reproduction and long-term health of offspring: the
      importance of one-carbon metabolism.
AB  - BACKGROUND Most reproductive failures originate during the periconceptional
      period and are influenced by the age and the lifestyle of parents-to-be. We
      advance the hypothesis that these failures can arise as a partial consequence of
      derangements to one-carbon (1-C) metabolism (i.e. metabolic pathways that utilize
      substrates/cofactors such as methionine, vitamin B12, folate). 1-C metabolic
      pathways drive the synthesis of proteins, biogenic amines and lipids required for
      early growth, together with the synthesis and methylation of DNA and histones
      essential for the regulation of gene expression. We review how deficiencies in
      periconceptional 1-C metabolism affect fertility and development together with
      underlying mechanisms derived from animal studies. METHODS A literature search
      was performed using PubMed and bibliographies of all relevant original research
      articles and reviews. RESULTS We define 'periconception' as a 5-6-month period in
      women embracing oocyte growth, fertilization, conceptus formation and development
      to Week 10 of gestation (coinciding with the closure of the secondary palate in
      the embryo). During this period significant epigenetic modifications to chromatin
      occur that correspond with normal development. Subtle variations in 1-C
      metabolism genes and deficiencies in 1-C substrates/cofactors together with poor
      lifestyle, such as smoking and alcohol consumption, disturb 1-C metabolism and
      contribute to subfertility and early miscarriage and compromise offspring health.
      Procedures used in assisted reproduction can also disturb these metabolic
      pathways and contribute to poor pregnancy outcomes. CONCLUSIONS Evidence
      presented indicates that parental nutrition and other lifestyle factors during
      the periconceptional period can affect reproductive performance via 1-C metabolic
      pathways. This knowledge provides opportunities for treatment and prevention of
      reproductive failures and future non-communicable diseases. 

PMID- 23959023
TI  - Prediction, events, and the advantage of agents: the processing of semantic roles
      in visual narrative.
AB  - Agents consistently appear prior to Patients in sentences, manual signs, and
      drawings, and Agents are responded to faster when presented in visual depictions
      of events. We hypothesized that this "Agent advantage" reflects Agents' role in
      event structure. We investigated this question by manipulating the depictions of
      Agents and Patients in preparatory actions in wordless visual narratives. We
      found that Agents elicited a greater degree of predictions regarding upcoming
      events than Patients, that Agents are viewed longer than Patients, independent of
      serial order, and that visual depictions of actions are processed more quickly
      following the presentation of an Agent vs. a Patient. Taken together these
      findings support the notion that Agents initiate the building of event
      representation. We suggest that Agent First orders facilitate the interpretation
      of events as they unfold and that the saliency of Agents within visual
      representations of events is driven by anticipation of upcoming events. 

PMID- 23959026
TI  - Minireview on Achillea millefolium Linn.
AB  - Yarrow (Achillea millefolium L.) is an important medicinal plant with different
      pharmaceutical uses. A. millefolium has been used for centuries to treat various
      diseases including malaria, hepatitis and jaundice. A. millefolium is commonly
      prescribed to treat liver disorders. It is also used as an anti-inflammatory
      agent and is a hepatoprotective herb. A. millefolium is considered safe for
      supplemental use. It has antihepatotoxic effects also. It is prescribed as an
      astringent agent. It is prescribed in hemorrhoids, headache, bleeding disorders,
      bruises, cough, influenza, pneumonia, kidney stones, high blood pressure,
      menstrual disorders, fever, rheumatoid arthritis, gout, osteoarthritis,
      hemorrhagic disorders, chicken pox, cystitis, diabetes mellitus, indigestion,
      dyspepsia, eczema, psoriasis and boils.

PMID- 23959025
TI  - Multilevel selection analysis of a microbial social trait.
AB  - The study of microbial communities often leads to arguments for the evolution of
      cooperation due to group benefits. However, multilevel selection models caution
      against the uncritical assumption that group benefits will lead to the evolution
      of cooperation. We analyze a microbial social trait to precisely define the
      conditions favoring cooperation. We combine the multilevel partition of the Price
      equation with a laboratory model system: swarming in Pseudomonas aeruginosa. We
      parameterize a population dynamics model using competition experiments where we
      manipulate expression, and therefore the cost-to-benefit ratio of swarming
      cooperation. Our analysis shows that multilevel selection can favor costly
      swarming cooperation because it causes population expansion. However, due to high
      costs and diminishing returns constitutive cooperation can only be favored by
      natural selection when relatedness is high. Regulated expression of cooperative
      genes is a more robust strategy because it provides the benefits of swarming
      expansion without the high cost or the diminishing returns. Our analysis supports
      the key prediction that strong group selection does not necessarily mean that
      microbial cooperation will always emerge. 

PMID- 23959027
TI  - Seed-mediated growth of jack-shaped gold nanoparticles from cyclodextrin-coated
      gold nanospheres.
AB  - Branched gold nanoparticles were prepared by a seed-mediated approach using per-6
      thio-6-deoxy-beta-cyclodextrin capped gold nanospheres as seeds and a growth
      medium similar to those commonly employed to prepare gold nanorods, containing
      AgNO3, ascorbic acid and cetyltrimethylammonium bromide. Novel jack-shaped gold
      nanoparticles (102-105 nm) were obtained at a specific range of Ag(+) ion
      concentrations (62-102 MUM). The crystalline structure of these nanoparticles was
      confirmed by high-resolution transmission electron microscopy. The influence of
      the perthiolated beta-cyclodextrin on the successful preparation of gold
      nanojacks was demonstrated. The jack-shaped gold nanoparticles showed strong
      absorption in the near infrared region and excellent catalytic activity for the
      electrochemical oxidation of H2O2. 

PMID- 23959028
TI  - The non-structural (NS) gene segment of H9N2 influenza virus isolated from
      backyard poultry in Pakistan reveals strong genetic and functional similarities
      to the NS gene of highly pathogenic H5N1.
AB  - Apart from natural reassortment, co-circulation of different avian influenza
      virus strains in poultry populations can lead to generation of novel variants and
      reassortant viruses. In this report, we studied the genetics and functions of a
      reassorted non-structural gene (NS) of H9N2 influenza virus collected from back
      yard poultry (BYP) flock. Phylogenetic reconstruction based on hemagglutinin and
      neuraminidase genes indicates that an isolate from BYP belongs to H9N2. However,
      the NS gene-segment of this isolate cluster into genotype Z, clade 2.2 of the
      highly pathogenic H5N1. The NS gene plays essential roles in the host-adaptation,
      cell-tropism, and virulence of influenza viruses. However, such interpretations
      have not been investigated in naturally recombinant H9N2 viruses. Therefore, we
      compared the NS1 protein of H9N2 (H9N2/NS1) and highly pathogenic H5N1 (H5N1/NS1)
      in parallel for their abilities to regulate different signaling pathways, and
      investigated the molecular mechanisms of IFN-beta production in human, avian, and
      mink lung cells. We found that H9N2/NS1 and H5N1/NS1 are comparably similar in
      inhibiting TNF-alpha induced nuclear factor kappaB and double stranded RNA
      induced activator protein 1 and interferon regulatory factor 3 transcription
      factors. Thus, the production of IFN-beta was inhibited equally by both NS1s as
      demonstrated by IFN stimulatory response element and IFN-beta promoter
      activation. Moreover, both NS1s predominantly localized in the nucleus when
      transfected to human A549 cells. This study therefore suggests the possible
      increased virulence of natural reassortant viruses for their efficient invasion
      of host immune responses, and proposes that these should not be overlooked for
      their epizootic and zoonotic potential. 

PMID- 23959029
TI  - Staphylococcus saprophyticus surface-associated protein (Ssp) is associated with
      lifespan reduction in Caenorhabditis elegans.
AB  - Staphylococcal lipases have been proposed as pathogenicity factors. In
      Staphylococcus saprophyticus the surface-associated protein (Ssp) has been
      previously characterized as a cell wall-associated true lipase. A S.
      saprophyticus Deltassp::ermB mutant has been described as less virulent in an in
      vivo model of urinary tract infection compared with its wild-type. This is the
      first report showing that S. saprophyticus induced a lifespan reduction in
      Caenorhabditis elegans similar to that of S. aureus RN4220. In two S.
      saprophyticus Deltassp::ermB mutants lifespan reduction in C. elegans was partly
      abolished. In order to attribute virulence to the lipase activity itself and
      distinguish this phenomenon from the presence of the Ssp-protein, the conserved
      active site of the lipase was modified by site-directed ligase-independent
      mutagenesis and lipase activity-deficient mutants were constructed. These results
      indicate that the Ssp is associated with pathogenicity in C. elegans and one
      could speculate that the lipase activity itself is responsible for this
      virulence. 

PMID- 23959030
TI  - Virulence profile: Alejandro Aballay.

PMID- 23959031
TI  - Immunotherapy for tularemia.
AB  - Francisella tularensis is a gram-negative bacterium that causes the zoonotic
      disease tularemia. Francisella is highly infectious via the respiratory route
      (~10 CFUs) and pulmonary infections due to type A strains of F. tularensis are
      highly lethal in untreated patients (> 30%). In addition, no vaccines are
      licensed to prevent tularemia in humans. Due to the high infectivity and
      mortality of pulmonary tularemia, F. tularensis has been weaponized, including
      via the introduction of antibiotic resistance, by several countries. Because of
      the lack of efficacious vaccines, and concerns about F. tularensis acquiring
      resistance to antibiotics via natural or illicit means, augmentation of host
      immunity, and humoral immunotherapy have been investigated as countermeasures
      against tularemia. This manuscript will review advances made and challenges in
      the field of immunotherapy against tularemia. 

PMID- 23959033
TI  - Delayed surgery in displaced paediatric supracondylar fractures: a safe approach?
      Results from a large UK tertiary paediatric trauma centre.
AB  - BACKGROUND: Displaced paediatric supracondylar humeral fractures pose a
      significant risk of neurovascular injury and consequently have traditionally been
      treated as a surgical emergency. Recently, the need for emergency surgery has
      been questioned. We wished to analyse our experience at a large UK tertiary
      paediatric trauma centre. METHODS: A retrospective case note review was performed
      on patients with Gartland Grades 2 and 3 supracondylar fractures observed in a 2
      year period from July 2008 to July 2010. We divided children into those treated
      before 12 h (early surgery) and after 12 h (delayed surgery). Analysis was
      undertaken using Fisher's exact test. RESULTS: Of the 137 patients, 115 were
      included in the study; median time-to-surgery was 15:30 (range 2:45-62:50);
      thirty-nine children were treated before 12 h and 76 patients after. In the early
      surgery group, three children (7.7%) developed a superficial pin-site infection,
      four children (10.3%) required open reduction, five children (12.8%) sustained an
      iatrogenic nerve injury, and two children (5%) required reoperation. In the
      delayed surgery group, one child (1.3%) had a superficial pin-site infection,
      four children (5.3%) required open reduction, seven children (9.2%) sustained an
      iatrogenic nerve injury, and two children (2.6%) reoperation. Bivariate analysis
      of our data using Fisher's exact t test revealed no statistically significant
      difference between early and delayed surgery groups with regard to infection
      rates (p = 0.1), iatrogenic nerve injury (p = 0.53) or need for open reduction (p
      = 0.44). CONCLUSION: Our results indicate that delayed surgery appears to offer a
      safe management approach in the treatment of displaced supracondylar fractures,
      but it is important that cases are carefully evaluated on an individual basis.
      These results indicate that patient transfer to a specialist paediatric centre,
      often with consequent surgical delay, is a safe management option and also
      negates the obligation to carry out these procedures at night.

PMID- 23959034
TI  - Paediatric lateral humeral condyle fractures: internal oblique radiographs alter
      the course of conservative treatment.
AB  - INTRODUCTION: At first presentation of paediatric humeral lateral condyle
      fractures, radiological methods such as computerised tomography, ultrasonography,
      magnetic resonance imaging, arthrography, and internal oblique radiography are
      used to determine stability. Very few studies show which radiological method
      should be used to evaluate displacement at follow-up for conservatively treated
      patients. This study aimed to show that internal oblique radiography is a simple,
      effective method to determine the subsequent development of fracture displacement
      in patients with an initially non-displaced or minimally displaced fracture.
      MATERIALS AND METHODS: In this retrospective study, 27 paediatric patients with
      non-displaced or minimally displaced (<2 mm) humerus lateral condyle fracture
      were evaluated by elbow anteroposterior radiograph. The degree of fracture
      displacement was evaluated by anteroposterior then by internal oblique
      radiographs. The first follow-up was made between the 5th and 8th day and
      thereafter at intervals of 7-10 days. RESULTS: Of the 27 patients identified with
      non-displaced or minimally displaced (<2 mm) fracture from the initial
      anteroposterior radiograph, 16 were accepted as displacement >2 mm as a result of
      the evaluation of the internal oblique radiography and underwent surgery. At
      follow-up, 2 of 11 patients were defined with displacement from anteroposterior
      and internal oblique radiographs and 4 from the internal oblique radiographs and
      underwent surgery. Conservative treatment was applied to 5 patients. CONCLUSIONS:
      Internal oblique radiography is the best imaging showing subsequent fracture
      displacement in initially non-displaced or minimally displaced humerus lateral
      condyle fractures. At the first week follow-up, anteroposterior and particularly
      internal oblique radiographs should be taken of conservatively treated patients.

PMID- 23959032
TI  - The staphylococcal enterotoxin (SE) family: SEB and siblings.
AB  - Staphylococcus aureus plays an important role in numerous human cases of food
      poisoning, soft tissue, and bone infections, as well as potentially lethal toxic
      shock. This common bacterium synthesizes various virulence factors that include
      staphylococcal enterotoxins (SEs). These protein toxins bind directly to major
      histocompatibility complex class II on antigen-presenting cells and specific
      Vbeta regions of T-cell receptors, resulting in potentially life-threatening
      stimulation of the immune system. Picomolar concentrations of SEs ultimately
      elicit proinflammatory cytokines that can induce fever, hypotension, multi-organ
      failure, and lethal shock. Various in vitro and in vivo models have provided
      important tools for studying the biological effects of, as well as potential
      vaccines/therapeutics against, the SEs. This review succinctly presents known
      physical and biological properties of the SEs, including various intervention
      strategies. In particular, SEB will often be portrayed as per biodefense concerns
      dating back to the 1960s. 

PMID- 23959035
TI  - Minimally invasive percutaneous plate osteosynthesis for ankle fractures: a
      prospective observational cohort study.
AB  - BACKGROUND: The gold standard for the surgical management of ankle fractures is
      through open reduction and internal fixation. The rate of wound problems has been
      reported to be as high as 18%, especially in patients with poor vascular supply
      or in diabetics. Minimally invasive percutaneous plate osteosynthesis (MIPPO) has
      been described as a potential solution for these patients. PATIENTS AND METHODS:
      This is a prospective observational cohort study. From October 2009 to February
      2010, and following ethical approval of our research, adult patients admitted at
      our level I trauma center with a closed lateral malleolar displaced unstable
      fracture (Lauge-Hansen supination-external rotation) with or without a medial
      sided injury and patients with an undisplaced fracture associated with medial
      clear space opening on external rotation stress radiographs were recruited and
      managed using MIPPO technique. All patients were followed up for a minimum of 12
      months post-surgery (12-20 with a mean of 16.5 months). Trauma mechanism,
      comorbidities, classifications, trauma-surgery interval, image intensifier
      duration, surgery duration, complications, and function American Orthopaedic Foot
      and Ankle Society (AOFAS) were analyzed. RESULTS: Thirty-two patients were
      recruited of which 20 fulfilled the inclusion criteria (16 females, 4 males) and
      were available for follow-up. Ten fractures (50%) were classified as 44-B1, 7
      fractures (35%) as 44-B2, and 3 fractures (15%) as 44-B3 according to the
      Arbeitsgemeinschaft fur Osteosynthesefragen/Orthopaedic Trauma Association
      classification (100% were supination-external rotation injuries). At 8 weeks post
      surgery, all fractures had healed. The duration of surgery ranged between 15 and
      73 min (average 32.8) from skin incision to closure. There were 2 complications
      (1 malunion and 1 skin necrosis requiring implant removal). At 12-month follow
      up, AOFAS average was 88.3 (72-100 standard deviation of 6.8 points). CONCLUSION:
      MIPPO technique proved to be a viable option for lateral malleolar fracture
      treatment with a low complication rate and high functional outcome at 1 year. It
      is particularly useful in patients with a high risk of wound complication.

PMID- 23959036
TI  - Sustained static stress-induced chondrocyte apoptosis in the rat   cervical
      vertebral growth plate and its signal transduction   mechanisms.
AB  - Apoptosis of the vertebral growth plate chondrocytes plays an important role in
      the pathogenesis of intervertebral disk degeneration. In this paper, we have
      successfully established an experimental model induced by static stress and
      provided a useful method to study the mechanisms of chondrocyte apoptosis.A
      sustained static load of C0.2 MPa over at least 12 h was observed to induce
      chondrocyte apoptosis, up-regulation of bax and caspase-3 expression, and down
      regulation of bcl-2 expression.

PMID- 23959037
TI  - Completing cremation forms: a practical guide.

PMID- 23959038
TI  - Management of medication in patients with Parkinson's disease who are nil-by
      mouth.

PMID- 23959039
TI  - Hand infections.

PMID- 23959040
TI  - [Current status and problems of the entirely subcutaneous ICD (S-ICD(r))].
AB  - Prevention of sudden cardiac death is one of the most important tasks of
      cardiology. Transvenous ICD-systems have impressively proven their effectiveness
      in numerous randomized trials. Transvenous systems have their limitations due to
      frequent long-term lead complications. Having been available for a few years, the
      entirely subcutaneous ICD-system (S-ICD(r), Boston Scientific, USA, former
      Cameron Health, USA) seems to be a promising alternative despite the lack of
      prospective data. The implantation of the SICD(r) can be performed easily; lead
      complications are rare because of the totally subcutaneous implantation. The
      detection and therapy of life-threatening tachyarrhythmias seems to be safe,
      although inappropriate therapies are a common problem in cases of insufficient
      ECG screening. S-ICD(r) is no alternative to the transvenous system due to
      limited programming options and the lack of stimulation, but it is an interesting
      supplement of ICD therapy.

PMID- 23959041
TI  - [Practical aspects of pacemaker and ICD-lead extractions].
AB  - Special tools for lead removal enables transvenous lead extractions without
      cardiac exposure. The risk of fatal complications during extraction of long-term
      implanted leads requires detailed knowledge and trained physicians. In addition
      to patients' age and gender, individual extraction risk factors are access and
      time since implantation, lead position, kind and number of leads. Locking stylets
      to anchor the lead within the lumen are necessary in all extraction procedures
      while the use of external sheaths is optional. Higher risk of cardiac or central
      vein perforation during lead mobilisation with external laser sheaths has to be
      respected, and these tools should be used with strong indication only. In cases
      of high risk, lead explantation with an open heart procedure should be considered
      as an alternative.

PMID- 23959043
TI  - The first latent green fluorophores for the detection of azoreductase activity in
      bacterial cultures.
AB  - An efficient synthesis of original bio-reductive probes suitable for the
      detection of azoreductases from the fluorescent rhodamine 110 dye is presented. A
      "turn-on" green fluorescence response upon reduction of the two diazo bonds of
      these latent fluorophores was observed both in vitro and in the context of
      bacterial cultures. 

PMID- 23959044
TI  - Cationic Rh and Ir complexes containing bidentate imidazolylidene-1,2,3-triazole
      donor ligands: synthesis and preliminary catalytic studies.
AB  - A series of new cationic Rh(I), Rh(III) and Ir(III) complexes containing hybrid
      bidentate N-heterocyclic carbene-1,2,3-triazolyl donor of general formulae
      [Rh(CaT)(COD)]BPh4 (2a-d), [Rh(CaT)(CO)2]BPh4 (3a-d) and [M(CaT)(Cp*)Cl]BPh4 (M =
      Rh, 4a-d; M = Ir, 5a-c), where CaT = bidentate N-heterocyclic carbene-triazolyl
      ligands, COD = 1,5-cyclooctadiene and Cp* = 1,2,3,4,5
      pentamethylcyclopentadienyl, were synthesised. The imidazolium-1,2,3-triazolyl
      pre-ligands (1a-c and 1e-i) were readily prepared using the Cu(I) catalysed
      'click reaction' between phenyl azide or benzyl azides with propargyl
      functionalised imidazolium salts. The single crystal solid state structures of
      complexes 2a-d; 3a-b; 4a-d and 5a-b confirm the bidentate coordination of the NHC
      1,2,3-triazolyl ligand with the NHC coordinating via the 'normal' C2-carbon and
      the 1,2,3-triazolyl donor coordinating via the N3' atom to form six membered
      metallocycles. These complexes are the first examples of Rh and Ir complexes
      containing the hybrid NHC-1,2,3-triazolyl ligands which exhibit a bidentate
      coordination mode. A number of these complexes showed limited efficiency as
      catalysts for the intramolecular hydroamination of 4-pentyn-1-amine to 2
      methylpyrroline.

PMID- 23959045
TI  - Asthma prevalence and humoral immune response in Somali immigrants in the US:
      implications for the hygiene hypothesis.

PMID- 23959046
TI  - Deprivation, winter season, and COPD exacerbations.

PMID- 23959047
TI  - Tumor necrosis factor-alpha-activated mesenchymal stem cells promote endothelial
      progenitor cell homing and angiogenesis.
AB  - Mesenchymal stem cells (MSCs) accelerate regeneration of ischemic or injured
      tissues by stimulation of angiogenesis through a paracrine mechanism. Tumor
      necrosis factor-alpha (TNF-alpha)-activated MSCs secrete pro-angiogenic
      cytokines, including IL-6 and IL-8. In the present study, using an ischemic
      hindlimb animal model, we explored the role of IL-6 and IL-8 in the paracrine
      stimulation of angiogenesis and tissue regeneration by TNF-alpha-activated MSCs.
      Intramuscular injection of conditioned medium derived from TNF-alpha-treated MSCs
      (TNF-alpha CM) into the ischemic hindlimb resulted in attenuated severe limb loss
      and stimulated blood perfusion and angiogenesis in the ischemic limb.
      Immunodepletion of IL-6 and IL-8 resulted in attenuated TNF-alpha CM-stimulated
      tissue repair, blood perfusion, and angiogenesis. In addition, TNF-alpha CM
      induced migration of human cord blood-derived endothelial progenitor cells (EPCs)
      through IL-6- and IL-8-dependent mechanisms in vitro. Intramuscular injection of
      TNF-alpha CM into the ischemic limb led to augmented homing of tail vein-injected
      EPCs into the ischemic limb in vivo and immunodepletion of IL-6 or IL-8 from TNF
      alpha CM attenuated TNF-alpha CM-stimulated homing of EPCs. In addition,
      intramuscular injection of recombinant IL-6 and IL-8 proteins resulted in
      increased homing of intravenously transplanted EPCs into the ischemic limb and
      improved blood perfusion in vivo. These results suggest that TNF-alpha CM
      stimulates angiogenesis and tissue repair through an increase in homing of EPCs
      through paracrine mechanisms involving IL-6 and IL-8. 

PMID- 23959049
TI  - Reference values for acute phase proteins in calves and its clinical application.

PMID- 23959048
TI  - Combined molecular MRI and immuno-spin-trapping for in vivo detection of free
      radicals in orthotopic mouse GL261 gliomas.
AB  - Free radicals play a major role in gliomas. By combining immuno-spin-trapping
      (IST) and molecular magnetic resonance imaging (mMRI), in vivo levels of free
      radicals were detected within mice bearing orthotopic GL261 gliomas. The nitrone
      spin trap DMPO (5,5-dimethyl pyrroline N-oxide) was administered prior to
      injection of an anti-DMPO probe (anti-DMPO antibody covalently bound to a bovine
      serum albumin (BSA)-Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)
      biotin MRI contrast agent) to trap tumor-associated free radicals. mMRI detected
      the presence of anti-DMPO adducts by either a significant sustained increase
      (p<0.001) in MR signal intensity or a significant decrease (p<0.001) in T1
      relaxation, measured as %T1 change. In vitro assessment of the anti-DMPO probe
      indicated a significant decrease (p<0.0001) in T1 relaxation in GL261 cells that
      were oxidatively stressed with hydrogen peroxide, compared to controls. The
      biotin moiety of the anti-DMPO probe was targeted with fluorescently-labeled
      streptavidin to locate the anti-DMPO probe in excised brain tissues. As a
      negative control a non-specific IgG antibody covalently bound to the albumin-Gd
      DTPA-biotin construct was used. DMPO adducts were also confirmed in tumor tissue
      from animals administered DMPO, compared to non-tumor brain tissue. GL261 gliomas
      were found to have significantly increased malondialdehyde (MDA) protein adducts
      (p<0.001) and 3-nitrotyrosine (3-NT) (p<0.05) compared to normal mouse brain
      tissue, indicating increased oxidized lipids and proteins, respectively. Co
      localization of the anti-DMPO probe with either 3-NT or 4-hydroxynonenal was also
      observed. This is the first report regarding the detection of in vivo levels of
      free radicals from a glioma model. 

PMID- 23959050
TI  - Interval between neoadjuvant chemoradiotherapy and surgery for esophageal
      squamous cell carcinoma: does delayed surgery impact outcome?
AB  - BACKGROUND: Although esophagectomy traditionally is recommended to perform within
      8 weeks after neoadjuvant chemoradiotherapy (nCRT), data from neoadjuvantly
      treated rectal cancer patients demonstrate that delayed surgery ([8 weeks) can
      maximize the effect of CRT. Despite these promising data, investigators are
      concerned that delayed surgery may lead to tumor repopulation. We report the
      impact of delayed surgery in patients with esophageal cancer who were treated
      with nCRT. METHODS: We retrospectively studied 276 esophageal cancer patients
      treated with nCRT and surgery between 2002 and 2008. We compared perioperative
      complication, rate of pathological complete response (pCR), distribution of tumor
      regression grade (TRG), and overall survival (OS) in patients who underwent
      surgery within 8 weeks (group A) and after 8 weeks (group B) after nCRT. RESULTS:
      There were 138 patients in each group with similar pre/post-nCRT characteristics.
      Delayed surgery did not result in lower surgical risk or higher pCR rate.
      Survival outcome also did not improve following a longer surgery interval (5-year
      OS: group A vs. group B, 29 vs. 23 %; P = 0.3). On the contrary, a subgroup
      analysis showed that delayed surgery might be hazardous, especially in patients
      who demonstrate a good response after nCRT. The amount of residual cancer, as
      measured by TRG, increased significantly after a longer surgical interval (P =
      0.024). Survival also decreased after a longer surgical interval (5-year OS B8
      vs. [8 weeks, 50 vs. 35 %; P = 0.038). CONCLUSIONS: After nCRT, esophagectomy
      should be performed within 8 weeks, especially in patients with good response.

PMID- 23959052
TI  - Postmastectomy irradiation for DCIS with narrow margins: not for the Festrunk
      Brothers.

PMID- 23959051
TI  - Impact of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial on
      clinical management of the axilla in older breast cancer patients: a SEER
      medicare analysis.
AB  - BACKGROUND: American College of Surgeons Oncology Group (ACOSOG) Z0011
      demonstrated that eligible breast cancer patients with positive sentinel lymph
      nodes (SLN) could be spared an axillary lymph node dissection (ALND) without
      sacrificing survival or local control. Although heralded as a ''practice-changing
      trial,'' some argue that the stringent inclusion criteria limit the trial's
      clinical significance. The objective was to assess the potential impact of ACOSOG
      Z0011 on axillary surgical management of Medicare patients and examine current
      practice patterns. METHODS: Medicare beneficiaries aged C66 years with
      nonmetastatic invasive breast cancer diagnosed from 2001 to 2007 were identified
      from the Surveillance, Epidemiology and End Results-Medicare database (n =
      59,431). Eligibility for ACOSOG Z0011 was determined: SLN mapping, tumor?5 cm, no
      neoadjuvant treatment, breast conservation; number of positive nodes was
      determined. Actual surgical axillary management for eligible patients was
      assessed. RESULTS: Twelve percent (6,942/59,431) underwent SLN mapping and were
      node positive. Overall, 2,637 patients (4.4 % (2,637/59,431) of the total cohort,
      but 38 % (2,637/6,942) of patients with SLN mapping and positive nodes) met
      inclusion criteria for ACOSOG Z0011, had 1 or 2 positive lymph nodes, and could
      have been spared an ALND. Of these 2,637 patients, 46 % received a completion
      ALND and 54 % received only SLN biopsy. CONCLUSIONS: Widespread implementation of
      ACOSOG Z0011 trial results could potentially spare 38 % of older breast cancer
      patients who undergo SLN mapping with positive lymph nodes an ALND. However, 54 %
      of these patients are already managed with SLN biopsy alone, lessening the impact
      of this trial on clinical practice in older breast cancer patients.

PMID- 23959053
TI  - Pathologic discordance of differentiation between endoscopic biopsy and
      postoperative specimen in mucosal gastric adenocarcinomas.
AB  - BACKGROUND: Tumor differentiation is a major determinant of endoscopic resection
      in mucosal gastric cancers, and the treatment decision is usually based on a
      preoperative endoscopic biopsy. However, in a proportion of patients, the
      pathologic assessment of differentiation differs between the endoscopic biopsy
      and postgastrectomy specimen. This discrepancy is important in that it may lead
      to an additional radical gastrectomy after endoscopic resection or unnecessary
      operation for patients who could have been treated with endoscopic resection.
      This study aimed to investigate the frequency of such cases and to identify risk
      factors for discordance in patients with mucosal gastric adenocarcinoma. METHODS:
      The clinicopathologic characteristics of 1,326 patients who underwent curative
      gastrectomy for mucosal gastric cancer at Asan Medical Center from 2007 to 2011
      were retrospectively reviewed. RESULTS: The overall discordance was 21.5 % (285
      cases), and clinically significant discordant rate was 11.9 % (157 cases). Ninety
      nine tumors (7.5 %) with differentiated histology on preoperative biopsy were
      found to be undifferentiated on postoperative pathology. Additionally, 58
      patients (4.4 %) with undifferentiated histology on preoperative biopsy exhibited
      differentiated histology postoperatively. Multivariate analysis revealed that
      age, sex, tumor location, size, and gross pattern were associated with overall
      pathologic discordance. In patients with clinically significant discordance, only
      tumor location (cardia) and size ([2 cm) were independent factors for
      discordance. CONCLUSIONS: Considering a high discordance rate of differentiation
      between biopsy samples and resected specimens in mucosal cancer in cardia,
      performing endoscopic resection for confirmative diagnosis of differentiation
      before total gastrectomy can be a good option.

PMID- 23959054
TI  - Clinical course of breast cancer patients with isolated sternal and full
      thickness chest wall recurrences treated with and without radical surgery.
AB  - BACKGROUND: The role and outcome of radical surgery in contemporary
      multidisciplinary management of breast cancer patients presenting with isolated
      sternal or fullthickness chest wall (SCW) recurrence are undefined compared with
      patients treated without surgery. METHODS: Detailed analyses of all patients with
      isolated SCW recurrence treated from 1992 to 2011 at a large cancer institution
      were performed. Univariate and multivariate comparisons of clinicopathologic and
      treatment characteristics were analyzed. Overall and progression-free survival
      were compared using the Kaplan-Meier method. RESULTS: Seventy-six patients were
      identified, 44 treated surgically and 32 nonsurgically. Overall survival at 5
      years was not statistically different between patients who underwent surgery and
      those who did not (30.6 and 49.6 %, respectively; P = 0.52) although patients
      selected for surgery presented with more advanced and biologically aggressive
      disease. Surgically treated patients were more likely to have triple-negative
      breast cancer at recurrence (52 vs. 17 %; P = 0.006). Among surgical patients, 95
      % received preoperative systemic therapy. Clinical response with systemic therapy
      was significantly different, with surgically treated patients more likely to have
      responsive or stable disease (54 vs. 25 %, P = 0.04). Complications related to
      radical surgical resection occurred in 25 % of patients. For hormone receptor
      positive recurrence, 5-year progression-free survival was significantly higher
      among surgical patients (46.3 vs. 14.5 %; P = 0.01). CONCLUSIONS: Among patients
      with isolated SCW recurrence, hormone receptor-positive recurrence is associated
      with improved survival. Systemic therapy should be the initial treatment, and
      clinical response can be used to help select patients who may benefit from
      radical resection.

PMID- 23959055
TI  - Evaluation of the usefulness of the indocyanine green clearance test for
      chemotherapy-associated liver injury in patients with colorectal cancer liver
      metastasis.
AB  - BACKGROUND: The indocyanine green (ICG) clearance test is reported to be useful
      for the preoperative evaluation of hepatic functional reserve. However, the ICG
      clearance test has not been sufficiently investigated in patients with colorectal
      liver metastasis after chemotherapy. The aim of the present study was to evaluate
      whether the ICG clearance test is a useful parameter for the preoperative
      detection of chemotherapy-associated liver injury. METHODS: Ninety-four patients
      undergoing liver resection for colorectal liver metastasis after chemotherapy
      were studied. The medical records for each case were retrospectively reviewed.
      They underwent pathological assessment to clarify the degree of histopathological
      liver injury of the nontumoral liver parenchyma. In addition, the correlation
      between the pathological score and the ICG retention rate at 15 min (ICG-R15) was
      analyzed. RESULTS: Sinusoidal injury was observed in the 31 of 94 patients.
      Steatohepatitis was observed in the 40 of 94 patients. There was no strong
      correlation between the preoperative ICG-R15 value and the sinusoidal
      pathological score (r = 0.117, P = 0.261). There was no strong correlation
      between the ICG-R15 and the nonalcoholic fatty liver disease activity score (r =
      0.215, P = 0.037). CONCLUSIONS: It was difficult to predict the degree of
      chemotherapy-associated liver injury by the preoperative ICG-R15 value. It is
      necessary to estimate the hepatic functional reserve based on a combination of
      several clinical indicators without relying on the ICG test, in order to perform
      a safe radical liver resection.

PMID- 23959057
TI  - Selective dehybridization of DNA-Au nanoconjugates using laser irradiation.
AB  - Plasmonic heating to trigger release of oligonucleotides from nanoconjugates is
      potentially useful for therapeutic purposes and designed assembly of DNA
      nanostructures. In the past, great controllability has been achieved by
      introducing distinctive absorption nanoparticle centers, where the anchoring bond
      (e.g., sulfur-gold bond) has been selectively broken. Instead of releasing the
      surface-bound duplex DNA via breakage of the gold-sulphur anchor bond, selective
      and non-destructive dehybridization of DNA under a "mild" condition on different
      gold nanoconjugates is demonstrated in this work. This finding will permit
      sequential dehybridization/release of DNA at specific regions of a complex
      system; thus it can be extended to control gene expression and to manipulate an
      assembly of highly organized DNA constructs. Particularly we show herein the
      feasibility of selectively dehybridizing DNA-Au nanoconjugates via localized
      plasmonic heating, which is accomplished by controlling the laser wavelength,
      power, and irradiation time. 

PMID- 23959056
TI  - Recurrence patterns and prognostic factors in patients with hepatocellular
      carcinoma in noncirrhotic liver: a multi-institutional analysis.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) primarily affects patients with a
      cirrhotic liver. Reports on the characteristics of patients with HCC in
      noncirrhotic liver, as well as predictors of recurrence and survival, are scarce.
      METHODS: Between 1992 and 2011, 334 patients treated for HCC in noncirrhotic
      liver were identified from three major hepatobiliary centers. Clinicopathological
      characteristics were analyzed and independent predictors of recurrence and
      overall survival were identified using Cox proportional hazards models. RESULTS:
      Median patient age was 58 years and 77 % were male. Most patients had a solitary
      (81 %) and poorly or undifferentiated tumor (56 %); median size was 6.5 cm. The
      majority of patients (96 %) underwent liver resection (microscopically negative
      margins in 94 %), whereas a few had transarterial chemoembolization or
      transplantation (4 %). Median recurrence-free survival (RFS) was 2.5 years, and 1
      and 5-year RFS was 71.1, and 35 %, respectively. Elevated alkaline phosphatase
      levels [hazards ratio (HR) = 1.82], poor tumor differentiation (HR = 1.4),
      macrovascular invasion (HR = 2.18), and the presence of satellite lesions (HR =
      1.9), or intrahepatic metastases (HR = 2.59) were independently associated with
      shorter RFS; in contrast, an intact tumor capsule independently prolonged RFS (HR
      = 0.46). Median overall survival was 5.9 years, and 1- and 5-year overall
      survival was 86.9, and 54.5 %, respectively. Tumor size >=5 cm (HR = 2.27),
      macrovascular (HR = 2.72) or adjacent organ invasion (HR = 3.34), and satellite
      lesions (HR = 2.18) were independently associated with shorter overall survival,
      whereas an intact tumor capsule showed a protective effect (HR = 0.51).
      CONCLUSIONS: Following resection of HCC in the setting of no cirrhosis, more than
      one-half of patients were alive after 5 years. However, even among patients with
      no cirrhosis, recurrence was common. Factors associated with RFS and overall
      survival included tumor characteristics, such as tumor capsule, satellite
      lesions, and vascular invasion.

PMID- 23959058
TI  - Influence of socio-demographic and diet determinants on the levels of mercury in
      preschool children from a Mediterranean island.
AB  - Mercury levels measured in 302 hair samples of 4 year-old children from Menorca
      (western Mediterranean Sea) are reported. Their concentrations, arithmetic mean
      1.4 MUg/g, ranging between 0.040 MUg/g and 10 MUg/g, were higher than in other
      children inland populations but lower than in previously studied island cohorts,
      e.g. Faroe, Madeira and Seychelles. 20% of the samples were above the WHO
      recommended values. Higher concentrations in females than males were observed.
      Frequent consumption of fish and other seafood were significantly related to the
      observed mercury concentrations. Oily fish was the main source of this pollutant
      but shellfish and squid consumption were also associated with high mercury
      concentrations. Maternal smoking, occupational status or previous siblings were
      also found to significantly influence the levels of this pollutant. McCarthy
      Scales of Children's Abilities used to assess children's motor and cognitive
      abilities did not show association with mercury concentrations at 4 years of age.

PMID- 23959059
TI  - Wet deposition of brominated flame retardants to the Great Lakes basin--status
      and trends.
AB  - This study examined the temporal and spatial trends in wet deposition of 19
      legacy and emerging brominated flame retardants (14 polybrominated diphenyl
      ethers (PBDEs), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE),
      decabromodiphenylethane (DBDPE), hexabromocyclododecane (HBCD) and
      pentabromoethylbenzene (PBEB)) at 9 sites in the Canadian Great Lakes between
      2004 and 2010. Concentrations of BDE-209 in wet deposition declined
      significantly. This indicates that the voluntary actions taken to phase out the
      use of BDE 209 in North America are having an immediate effect on its environment
      concentrations. The analysis also revealed the presence of 22 short-term high
      concentration events that dominated overall wet deposition loadings of current
      use BFRs to the lakes. For instance, one sample in 2007 was responsible for 37%
      of the total loadings of HBCD to Lake Huron over the entire six-year sampling
      period. This questions the current paradigm of how we believe such pollutants
      enter the environment. 

PMID- 23959060
TI  - Statement of ESMINT and ESNR regarding recent trials evaluating the endovascular
      treatment at the acute stage of ischemic stroke.

PMID- 23959061
TI  - A systematic approach for identifying and presenting mechanistic evidence in
      human health assessments.
AB  - Clear documentation of literature search and presentation methodologies can
      improve transparency in chemical hazard assessments. We sought to improve clarity
      for the scientific support for cancer mechanisms of action using a systematic
      approach to literature retrieval, selection, and presentation of studies. The
      general question was "What are the mechanisms by which a chemical may cause
      carcinogenicity in the target tissue?". Di(2-ethylhexyl)phthalate was used as a
      case study chemical with a complex database of >3000 publications. Relevant
      mechanistic events were identified from published reviews. The PubMed search
      strategy included relevant synonyms and wildcards for DEHP and its metabolites,
      mechanistic events, and species of interest. Tiered exclusion/inclusion criteria
      for study pertinence were defined, and applied to the retrieved literature.
      Manual curation was conducted for mechanistic events with large literature
      databases. Literature trees documented identification and selection of the
      literature evidence. The selected studies were summarized in evidence tables
      accompanied by succinct narratives. Primary publications were deposited into the
      Health and Environmental Research Online (http://hero.epa.gov/) database and
      identified by pertinence criteria and key terms to permit organized retrieval.
      This approach contributes to human health assessment by effectively managing a
      large volume of literature, improving transparency, and facilitating subsequent
      synthesis of information across studies. 

PMID- 23959062
TI  - Aspects of the design protocol and the statistical methods for analysis of tar,
      nicotine and carbon monoxide yields in cigarette smoke that can affect the
      measurement variability within collaborative studies.
AB  - Statistical principles described in ISO 5725-1 (1994) are a robust basis for
      evaluating cigarette smoke data from collaborative studies under the ISO 3308
      machine smoking and for specifying the criteria for the removal of outlier data
      and determination of mean yields and their variability. However, the standard
      only provides recommendations on outlier removal that should be taken into
      account by experts who undertake data interpretation. The potential for over
      interpretation of data from small numbers of laboratories is highlighted and
      recommendations made to deal with this possibility. Key variables to the
      statistical analysis, the number of cigarettes per replicate and replicates
      performed in each laboratory, the number of participating laboratories and the
      use of linear and rotary smoking machines in smoke collection, are identified and
      their relevance to obtaining robust data are considered. The statistical methods
      routinely used for data analysis from the ISO regime, are re-assessed for their
      suitability to analyse data obtained under the Canadian intense (CI) regime,
      where yield differences between linear and rotary smoking machines are found.
      This machine effect can lead to more outliers being detected and difficulties in
      outlier detection which may affect the provision of robust estimates of mean
      yields, repeatability and reproducibility. 

PMID- 23959063
TI  - Role of obesity on all-cause mortality in whites with type 2 diabetes from Italy.
AB  - Mortality rate of diabetic patients is twice as much that of non-diabetic
      individuals. The role of obesity on mortality risk in patients with type 2
      diabetes is controversial. Aim of our study was to address the relationship
      between obesity and all-cause mortality in a real-life set of white patients with
      type 2 diabetes from central-southern Italy from the Gargano Mortality Study
      (GMS). In addition, we used genetic data from genome-wide association studies
      (GWAs)-derived single nucleotide polymorphisms (SNPs) firmly associated with body
      mass index (BMI), in order to investigate the intrinsic nature of reduced
      mortality rate we, in fact, observed in obese patients. Study subjects with type
      2 diabetes (n = 764) are part of the GMS, which is aimed at unraveling predictors
      of incident all-cause mortality. Time-to-death analyses were performed by Cox
      regression. Association between genotype risk score and obesity was tested by
      logistic regression. Of the 32 SNPs firmly associated with BMI, we investigated
      those with BMI beta value >=0.10 kg/m(2) and allele frequency >=10 %. Genotyping
      was performed by KBioscience (http://www.lgcgenomics.com/). In GMS, obesity
      predicted a 45 % reduction in all-cause mortality. Individuals with high "obesity
      genetic load" (i.e., those carrying >9 risk alleles) were 60 % more likely to be
      obese as compared to individuals with low "obesity genetic load." Most
      importantly, mortality rate was not different in individuals with high and low
      "obesity genetic load," thus indicating no role of obesity genes on all-cause
      mortality and speaking against a cause-effect relationship underlying the
      association between obesity and reduced mortality rate.

PMID- 23959064
TI  - No evidence for a local renin-angiotensin system in liver mitochondria.
AB  - The circulating, endocrine renin-angiotensin system (RAS) is important to
      circulatory homeostasis, while ubiquitous tissue and cellular RAS play diverse
      roles, including metabolic regulation. Indeed, inhibition of RAS is associated
      with improved cellular oxidative capacity. Recently it has been suggested that an
      intra-mitochondrial RAS directly impacts on metabolism. Here we sought to
      rigorously explore this hypothesis. Radiolabelled ligand-binding and unbiased
      proteomic approaches were applied to purified mitochondrial sub-fractions from
      rat liver, and the impact of AngII on mitochondrial function assessed. Whilst
      high-affinity AngII binding sites were found in the mitochondria-associated
      membrane (MAM) fraction, no RAS components could be detected in purified
      mitochondria. Moreover, AngII had no effect on the function of isolated
      mitochondria at physiologically relevant concentrations. We thus found no
      evidence of endogenous mitochondrial AngII production, and conclude that the
      effects of AngII on cellular energy metabolism are not mediated through its
      direct binding to mitochondrial targets. 

PMID- 23959065
TI  - Thiolate-protected Ag32 clusters: mass spectral studies of composition and
      insights into the Ag-thiolate structure from NMR.
AB  - Clusters composed of a 32 silver atom core, protected with thiolates of
      glutathione (GSH) and N-(2-mercaptopropionyl)glycine (MPGH), were synthesized by
      a solid-state route in milligram scale. They do not exhibit surface plasmon
      resonance unlike their larger sized nanoparticle analogues but show molecule-like
      features in absorption and luminescence spectra, falling in the visible window.
      The compositions Ag32SG19 (SG: thiolate of glutathione) and Ag32MPG19 (MPG:
      thiolate of MPGH) were identified from electrospray ionization mass spectrometry
      (ESI MS). Matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS) was not successful for -SG protected clusters as reported before, but for
      Ag32MPG19 a peak at 6.1 kDa was seen at a threshold laser intensity. This peak
      shifted to low mass region with increasing laser intensity due to systematic
      losses of Ag2S. Further confirmation of the composition Ag32SG19 was made using
      various studies such as XPS and EDAX. One-dimensional (1D) and two-dimensional
      (2D) NMR spectroscopic investigations of Ag32SG19 provided interesting spectral
      features which indicated the dominant -[SR-Ag-SR]- structural motif. This
      structural motif as the predominant entity is found for the first time in silver
      clusters.

PMID- 23959067
TI  - Dynamic photopatterning of cells in situ by Q-switched neodymium-doped yttrium
      ortho-vanadate laser.
AB  - Cellular micropattering has been increasingly adopted in quantitative biological
      experiments. A Q-switched pulsed neodymium-doped yttrium ortho-vanadate (Nd?YVO4)
      laser directed in-situ microfabrication technique for cell patterning is
      presented. A platform is designed uniquely to achieve laser ablation. The
      platform is comprised of thin gold coating over a glass surface that functions as
      a thermal transducer and is over-layered by a cell repellant polymer layer.
      Micropatterns are engraved on the platform, subsequently exposing specific cell
      adhesive micro-domains by ablating the gold-polymer coating photothermally.
      Experimental results indicate that the proposed approach is applicable under
      culture conditions, viable toward cells, and has a higher engraving speed.
      Possible uses in arraying isolated single cells on the platform are also shown.
      Additionally, based on those micro-patterns, dynamic cellular morphological
      changes and migrational speed in response to geometrical barriers are studied to
      demonstrate the potential applications of the proposed approach. Our results
      further demonstrate that cells in narrower geometry had elongated shapes and
      higher migrational speed than those in wider geometry. Importantly, the proposed
      approach will provide a valuable reference for efforts to study single cell
      dynamics and cellular migration related processes for areas such as cell
      division, wound healing, and cancer invasion.

PMID- 23959066
TI  - Prenatal stress changes the glycoprotein GPM6A gene expression and induces
      epigenetic changes in rat offspring brain.
AB  - Prenatal stress (PS) exerts strong impact on fetal brain development and on adult
      offspring brain functions. Previous work demonstrated that chronic stress alters
      the mRNA expression of GPM6A, a neuronal glycoprotein involved in filopodium
      extension. In this work, we analyzed the effect of PS on gpm6a expression and the
      epigenetic mechanisms involved. Pregnant Wistar rats received restraint stress
      during the last week of gestation. Male offspring were sacrificed on postnatal
      days 28 and 60. Hippocampus and prefrontal cortex samples were analyzed for gene
      expression (qPCR for mRNAs and microRNAs), methylation status (bisulfite
      conversion) and protein levels. Hippocampal neurons in culture were used to
      analyze microRNA overexpression effects. Prenatal stress induced changes in gpm6a
      levels in both tissues and at both ages analyzed, indicating a persistent effect.
      Two CpG islands in the gpm6a gene were identified. Variations in the methylation
      pattern at three specific CpGs were found in hippocampus, but not in PFC samples
      from PS offspring. microRNAs predicted to target gpm6a were identified in silico.
      qPCR measurements showed that PS modified the expression of several microRNAs in
      both tissues, being microRNA-133b the most significantly altered. Further studies
      overexpressing this microRNA in neuronal cultures showed a reduction in gmp6a
      mRNA and protein level. Moreover filopodium density was also reduced, suggesting
      that GPM6A function was affected. Gestational stress affected gpm6a gene
      expression in offspring likely through changes in methylation status and in
      posttranscriptional regulation by microRNAs. Thus, our findings propose gpm6a as
      a novel target for epigenetic regulation during prenatal stress. 

PMID- 23959069
TI  - Impact of spinal imbalance and BMI on lumbar spinal canal stenosis determined by
      a diagnostic support tool: cohort study in community-living people.
AB  - INTRODUCTION: The Japanese Society for Spine Surgery and Related Research (JSSR)
      developed a diagnostic support tool (score range -2 to 16) for lumbar spinal
      canal stenosis (LSS). It is well known that patients with LSS have a forward
      bending posture while walking. We could find only one study which examined
      sagittal alignment of LSS patients. The objectives of this study were to screen
      community-living people with LSS, and to investigate the association between LSS
      and spinal sagittal alignment, range of motion (ROM), and other spinal or
      physical factors. MATERIALS AND METHODS: We enrolled 286 subjects >=50 years old
      in the study. We regarded those with a JSSR diagnostic risk score >=7 as having
      LSS. We measured and evaluated lateral lumbar radiographs, sagittal parameters,
      sagittal balance, and spinal mobility as determined with SpinalMouse(r), back
      muscle strength (BMS), and body mass index (BMI). Spinal inclination angle (SIA)
      was used as an index of sagittal balance. RESULTS: Multivariate logistic
      regression analysis indicated that increased BMI (OR 1.121, p < 0.05) and SIA (OR
      1.144, p < 0.05) were important relevant factors for LSS. BMI had significant
      positive correlations with SIA (r = 0.214), and thoracic and lumbar kyphosis
      angles (r = 0.283, 0.131), and negative correlations with sacral slope angle (r =
      -0.166), and lumbar and total spinal ROMs (r = -0.270, -0.166). SIA had
      significant positive correlations with age (r = 0.334), BMI (r = 0.214) and
      lumbar kyphosis angle (r = 0.525), and negative correlations with BMS (r = 
      0.268), and lumbar and total spinal ROMs (r = -0.184, -0.171). CONCLUSIONS:
      Increased SIA and BMI might be the most relevant risk factors for LSS.

PMID- 23959070
TI  - Total knee replacement following high tibial osteotomy versus total knee
      replacement without high tibial osteotomy: a systematic review and meta analysis.
AB  - INTRODUCTION: Currently, there is no consensus as to whether total knee
      replacement(TKR) following high tibial osteotomy(HTO) provides similar
      postoperative outcomes as compared to TKR without previous HTO. Previous studies
      have provided limited evidence to small sample sizes and methodological
      inappropriateness. METHODS: A systematic search process was conducted utilising
      PRISMA guidelines. Electronic, peer reviewed and published literatures were
      searched. Databases searched include Embase, Medline, Cochrane Library, PubMed
      and cross references. Methodological appropriateness was assessed with
      Papadokastakis system and Critical Appraisal Skills questionnaire. Data were
      analysed for both clinical and statistical homogeneity. Meta analytic pooling was
      subsequently performed. RESULTS: 11 studies including 2170 TKR procedures were
      analysed for systematic review. The study (TKR following previous HTO) and
      control (TKR without previous HTO) groups were adequately matched for age, sex
      ratio and follow-up. Meta analysis of six studies utilising KSS system and four
      studies utilising HSS system showed no significant (p > 0.05) difference between
      the two groups. Complications also showed no significant difference between the
      two groups. At an average follow-up of 7.2 years, with revision arthroplasty for
      any cause as the endpoint, survivorship for the study and control groups was 95
      and 97 %, respectively. For revision arthroplasty with aseptic loosening as the
      end point, the survivorship was 98 % for both groups. CONCLUSION: Systematic
      review and meta analysis suggested that TKR following HTO provides similar
      outcomes as compared to TKR without previous HTO. Therefore, a previous HTO does
      not negatively influence a future TKR, though the conversion process of HTO to
      TKR is technically challenging. Systematic review also identified paucity in
      prospective and long term studies.

PMID- 23959071
TI  - What is the enemy in CME, conflicts of interest or bias?

PMID- 23959072
TI  - An application for impedance spectroscopy in the characterisation of the glass
      transition during the lyophilization cycle: the example of a 10% w/v maltodextrin
      solution.
AB  - Impedance spectroscopy has been used for the measurement of the glass transition
      of a 10 % maltodextrin solution contained within a glass vial, with externally
      attached electrodes. Features of the pseudo-relaxation process, associated with
      the composite impedance of the glass vial-solution assembly, were characterised
      by the peak amplitude, C(peak)("), and peak frequency, f(peak), of the
      capacitance spectra and the equivalent circuit elements that model the impedance
      spectra (i.e. the solution resistance and solution capacitance) and monitored
      every 3 min during re-heating of the solution. The time derivatives of all four
      parameters studied provided a glass transition in close agreement with DSC
      measurements (-17  degrees C) and at a precision of +/- 0.5  degrees C. The
      temperature dependencies of the solution resistance and peak frequency were then
      characterised with the Arrhenius and Vogel-Fulcher-Tammann fit functions, at
      temperatures below and above Tg, respectively. The energy of activation (below
      Tg) was estimated at ~20 kJ mol(-1), and the fragility index (If) of the glass
      forming liquid (above Tg) was estimated at 0.9. The significance of the fragility
      index to the development, optimisation and control of the freeze-drying cycle is
      highlighted.

PMID- 23959074
TI  - Elucidating a twin-dependent chemical activity of hierarchical copper sulfide
      nanocages.
AB  - We have demonstrated significant evidence of a solvent-dependent synthesis of
      hierarchical Cu7S4 polycrystalline nanocage assemblies with controllable
      aggregation-based building blocks by a sacrificial Cu2O template approach. The
      formation of a hierarchical Cu7S4 polycrystalline nanocage is essentially
      determined by a Kirkendall effect, which is attributed to the tailored
      aggregation behaviour of the nanoscale building blocks during the
      replacement/etching process in different polarities of solvent. The hierarchical
      Cu7S4 polycrystalline nanocage assembly of nanoparticle building blocks was
      prepared in pure water, while the hierarchical Cu7S4 polycrystalline nanocage
      assembly of twinned nanoplate building blocks was successfully synthesized in an
      anhydrous ethanol capping environment. Such a hierarchical Cu7S4 polycrystalline
      nanocage assembly of twinned nanoplate building blocks exhibits a higher
      photocatalytic activity than that of the common polycrystalline ones. A nanotwin
      dependent photochemical mechanism has been proposed. Significantly, this study is
      of great importance in bottom-up assembly of controllable ordered architectures,
      and offers a good opportunity to understand the fundamental importance of the
      formation mechanism and growth process of hierarchical Cu7S4 polycrystalline
      nanocages with controllable aggregation-based building blocks. 

PMID- 23959073
TI  - Proapoptotic peptide-mediated cancer therapy targeted to cell surface p32.
AB  - Antiangiogenic therapy is a promising new treatment modality for cancer, but it
      generally produces only transient tumor regression. We have previously devised a
      tumor-targeted nanosystem, in which a pentapeptide, CGKRK, delivers a
      proapoptotic peptide into the mitochondria of tumor blood vessel endothelial
      cells and tumor cells. The treatment was highly effective in glioblastoma mouse
      models completely refractory to other antiangiogenic treatments. Here, we
      identify p32/gC1qR/HABP, a mitochondrial protein that is also expressed at the
      cell surface of activated (angiogenic) endothelial cells and tumor cells, as a
      receptor for the CGKRK peptide. The results demonstrate the ability of p32 to
      cause internalization of a payload bound to p32 into the cytoplasm. We also show
      that nardilysin, a protease capable of cleaving CGKRK, plays a role in the
      internalization of a p32-bound payload. As p32 is overexpressed and surface
      displayed in breast cancers, we studied the efficacy of the nanosystem in this
      cancer. We show highly significant treatment results in an orthotopic model of
      breast cancer. The specificity of cell surface p32 for tumor-associated cells,
      its ability to carry payloads to mitochondria, and the efficacy of the system in
      important types of cancer make the nanosystem a promising candidate for further
      development.

PMID- 23959075
TI  - A human strain of Oxalobacter (HC-1) promotes enteric oxalate  secretion in the
      small intestine of mice and reduces urinary  oxalate excretion.
AB  - Enteric oxalate secretion that correlated with reductions in urinary oxalate
      excretion was previously reported in a mouse model of primary hyperoxaluria, and
      in wild type (WT) mice colonized with a wild rat strain (OXWR) of Oxalobacter (Am
      J Physiol 300:G461-G469, 2010). Since a human strain of the bacterium is more
      likely to be clinically used as a probiotic therapeutic, we tested the effects of
      HC-1 in WT. Following artificial colonization of WT mice with HC-1, the bacteria
      were confirmed to be present in the large intestine and, unexpectedly, detected
      in the small intestine for varying periods of time. The main objective of the
      present study was to determine whether the presence of HC-1 promoted intestinal
      secretion in the more proximal segments of the gastrointestinal tract. In
      addition, we determined whether HC-1 colonization led to reductions in urinary
      oxalate excretion in these mice. The results show that the human Oxalobacter
      strain promotes a robust net secretion of oxalate in the distal ileum as well as
      in the caecum and distal colon and these changes in transport correlate with the
      beneficial effect of reducing renal excretion of oxalate. We conclude that OXWR
      effects on intestinal oxalate transport and oxalate homeostasis are not unique to
      the wild rat strain and that, mechanistically, HC-1 has significant potential for
      use as a probiotic treatment for hyperoxaluria especially if it is also targeted
      to the upper and lower gastrointestinal tract.

PMID- 23959076
TI  - Development, triploblastism, physics of wetting and the Cambrian explosion.
AB  - The Cambrian explosion is characterized by the sudden outburst of organized
      animal plans, which occurred circa 530 M years ago. Around that time, many forms
      of animal life appeared, including several which have since disappeared. There is
      no general consensus about "why" this happened, and why it had any form of
      suddenness. However, all organized animal plans share a common feature: they are
      triploblastic, i.e., composed of 3 layers of tissue, endoderm, ectoderm and
      mesoderm. I show here that, within simple hypotheses, the formation of the
      mesoderm has intrinsically a physical exponential dynamics, leading rapidly to
      triploblastism, and eventually, to animal formation. A novel physico-mathematical
      framework including epithelium-mesenchyme transition, visco-elastic constitutive
      equations, and conservation laws, is presented which allows one to describe
      gastrulation as a self-wetting phenomenon of a soft solid onto itself. This
      phenomenon couples differentiation and migration during gastrulation, and leads
      in a closed form to an exponential scaling law for the formation of the mesoderm.
      Therefore, the Cambrian explosion might have started, actually, by a true
      viscoelastic "explosion": the exponential run-away of mesenchymal cells.

PMID- 23959077
TI  - Cross-linked conjugated polymer assemblies at the air-water interface through
      supramoleculer bundling.
AB  - We demonstrated conjugated polymer assemblies formed by coordination interaction
      with a porphyrinatozinc cross-linker at the air-water interface by means of the
      Langmuir-Blodgett technique. The coordination bonds were maintained at the
      interface, though the spacing between the polymer backbones in the Langmuir film
      was smaller than that in bulk solution, probably because of the influence of the
      interface. The successful transfer of the films to a substrate enabled the
      fabrication of a large-scale conjugated polymer material. 

PMID- 23959078
TI  - Neonatal overnutrition in mice exacerbates high-fat diet-induced metabolic
      perturbations.
AB  - Neonatal overnutrition results in accelerated development of high-fat diet (HFD)
      induced metabolic defects in adulthood. To understand whether the increased
      susceptibility was associated with aggravated inflammation and dysregulated lipid
      metabolism, we studied metabolic changes and insulin signaling in a chronic
      postnatal overnutrition (CPO) mouse model. Male Swiss Webster pups were raised
      with either three pups per litter to induce CPO or ten pups per litter as control
      (CTR) and weaned to either low-fat diet (LFD) or HFD. All animals were killed on
      the postnatal day 150 (P150) except for a subset of mice killed on P15 for the
      measurement of stomach weight and milk composition. CPO mice exhibited
      accelerated body weight gain and increased body fat mass prior to weaning and the
      difference persisted into adulthood under conditions of both LFD and HFD. As
      adults, insulin signaling was more severely impaired in epididymal white adipose
      tissue (WAT) from HFD-fed CPO (CPO-HFD) mice. In addition, HFD-induced
      upregulation of pro-inflammatory cytokines was exaggerated in CPO-HFD mice.
      Consistent with greater inflammation, CPO-HFD mice showed more severe macrophage
      infiltration than HFD-fed CTR (CTR-HFD) mice. Furthermore, when compared with CTR
      HFD mice, CPO-HFD mice exhibited reduced levels of several lipogenic enzymes in
      WAT and excess intramyocellular lipid accumulation. These data indicate that
      neonatal overnutrition accelerates the development of insulin resistance and
      exacerbates HFD-induced metabolic defects, possibly by worsening HFD-induced
      inflammatory response and impaired lipid metabolism. 

PMID- 23959080
TI  - Cafeteria diet inhibits insulin clearance by reduced insulin-degrading enzyme
      expression and mRNA splicing.
AB  - Insulin clearance plays a major role in glucose homeostasis and insulin
      sensitivity in physiological and/or pathological conditions, such as obesity
      induced type 2 diabetes as well as diet-induced obesity. The aim of the present
      work was to evaluate cafeteria diet-induced obesity-induced changes in insulin
      clearance and to explain the mechanisms underlying these possible changes. Female
      Swiss mice were fed either a standard chow diet (CTL) or a cafeteria diet (CAF)
      for 8 weeks, after which we performed glucose tolerance tests, insulin tolerance
      tests, insulin dynamics, and insulin clearance tests. We then isolated pancreatic
      islets for ex vivo glucose-stimulated insulin secretion as well as liver,
      gastrocnemius, visceral adipose tissue, and hypothalamus for subsequent protein
      analysis by western blot and determination of mRNA levels by real-time RT-PCR.
      The cafeteria diet induced insulin resistance, glucose intolerance, and increased
      insulin secretion and total insulin content. More importantly, mice that were fed
      a cafeteria diet demonstrated reduced insulin clearance and decay rate as well as
      reduced insulin-degrading enzyme (IDE) protein and mRNA levels in liver and
      skeletal muscle compared with the control animals. Furthermore, the cafeteria
      diet reduced IDE expression and alternative splicing in the liver and skeletal
      muscle of mice. In conclusion, a cafeteria diet impairs glucose homeostasis by
      reducing insulin sensitivity, but it also reduces insulin clearance by reducing
      IDE expression and alternative splicing in mouse liver; however, whether this
      mechanism contributes to the glucose intolerance or helps to ameliorate it
      remains unclear. 

PMID- 23959081
TI  - Altered topological patterns of large-scale brain functional networks during
      passive hyperthermia.
AB  - In this study, we simulated environmental heat exposure to 18 participants, and
      obtained functional magnetic resonance image (fMRI) data during resting state.
      Brain functional networks were constructed over a wide range of sparsity
      threshold according to a prior atlas dividing the whole cerebrum into 90 regions.
      Results of graph theoretical approaches showed that although brain networks in
      both normal and hyperthermia conditions exhibited economical small-world
      property, significant alterations in both global and nodal network metrics were
      demonstrated during hyperthermia. Specifically, a lower clustering coefficient,
      maintained shortest path length, a lower small-worldness, a lower mean local
      efficiency were found, indicating a tendency shift to a randomized network.
      Additionally, significant alterations in nodal efficiency were found in bilateral
      gyrus rectus, bilateral parahippocampal gyrus, bilateral insula, right caudate
      nucleus, bilateral putamen, left temporal pole of middle temporal gyrus, right
      inferior temporal gyrus. In consideration of physiological system changes, we
      found that the alterations of normalized clustering coefficient, small-worldness,
      mean normalized local efficiency were significantly correlated with the rectal
      temperature alteration, but failed to obtain significant correlations with the
      weight loss. More importantly, behavioral attention network test (ANT) after MRI
      scanning showed that the ANT effects were altered and correlated with the
      alterations of some global metrics (normalized shortest path length and
      normalized global efficiency) and prefrontal nodal efficiency (right dorsolateral
      superior frontal gyrus, right middle frontal gyrus and left orbital inferior
      frontal gyrus), implying behavioral deficits in executive control effects and
      maintained alerting and orienting effects during passive hyperthermia. The
      present study provided the first evidence for human brain functional disorder
      during passive hyperthermia according to graph theoretical analysis using resting
      state fMRI. 

PMID- 23959079
TI  - Cartilage to bone transitions in health and disease.
AB  - Aberrant redeployment of the 'transient' events responsible for bone development
      and postnatal longitudinal growth has been reported in some diseases in what is
      otherwise inherently 'stable' cartilage. Lessons may be learnt from the molecular
      mechanisms underpinning transient chondrocyte differentiation and function, and
      their application may better identify disease aetiology. Here, we review the
      current evidence supporting this possibility. We firstly outline endochondral
      ossification and the cellular and physiological mechanisms by which it is
      controlled in the postnatal growth plate. We then compare the biology of these
      transient cartilaginous structures to the inherently stable articular cartilage.
      Finally, we highlight specific scenarios in which the redeployment of these
      embryonic processes may contribute to disease development, with the foresight
      that deciphering those mechanisms regulating pathological changes and loss of
      cartilage stability will aid future research into effective disease-modifying
      therapies. 

PMID- 23959082
TI  - Evidence for spatial navigational impairments in hydrocephalus patients without
      spina bifida.
AB  - The cognitive sequelae of hydrocephalus have mostly been explored with
      standardised clinical tasks. The aim of the present research was determine
      whether impairments on these abstract tasks extend to everyday spatial and
      navigational behaviour. Patients with hydrocephalus, but without spina bifida,
      were compared to a control group on tests of searching behaviour, landmark
      memory, route learning, and path integration. Participants with hydrocephalus
      displayed reduced sensitivity to spatial cueing, less accurate route-learning,
      and significantly less accurate spatial updating. These data represent an
      important empirical demonstration of spatial navigational impairments due to
      hydrocephalus outside of the context of spina bifida. We discuss some of the
      cognitive, neural, and individual differences factors that might contribute to
      this particular pattern of impairments. 

PMID- 23959083
TI  - Effectiveness of the gold standard programmes (GSP) for smoking cessation in
      pregnant and non-pregnant women.
AB  - BACKGROUND: Smoking is considered the most important preventable risk factor in
      relation to the development of complications during pregnancy and delivery. The
      aim of this study was to evaluate the effectiveness of an intensive 6-week gold
      standard programme (GSP) on pregnant women in real life. METHODS: This was a
      prospective cohort study based on data from a national Danish registry on smoking
      cessation interventions. The study population included 10,682 women of a fertile
      age. The pregnancy status of the study population was identified using the
      National Patient Registry. RESULTS: The response rate to follow up was 76%. The
      continuous abstinence rate for both pregnant and non-pregnant smokers was 24-32%.
      The following prognostic factors for continuous abstinence were identified:
      programme format (individual/group), older age, heavy smoking, compliance with
      the programme, health professional recommendation, and being a disadvantaged
      smoker. CONCLUSIONS: The GSP seems to be as effective among pregnant smokers as
      among non-pregnant smoking women. Due to the relatively high effect and clinical
      significance, the GSP would be an attractive element in smoking cessation
      intervention among pregnant women.

PMID- 23959084
TI  - Longitudinal 2-year follow-up on the effect of a non-randomised school-based
      physical activity intervention on reducing overweight and obesity of Czech
      children aged 10-12 years.
AB  - BACKGROUND: This study assessed whether the benefits of a 2-year longitudinal non
      randomised school-based physical activity (PA) intervention programme to reduce
      overweight and obesity were still apparent two years after completion of the
      controlled intervention. METHODS: The study involved 84 girls (G) and 92 boys (B)
      aged 10-12 years who had participated in the PA intervention in 2006-2008 as 6-
      to 9-year olds and were included in the intervention (I) (43 G and 45 B) and the
      control (C) groups (41 G and 47 B). Participants' overweight/obesity was assessed
      using the percentile graph of Body Mass Index (BMI) from the World Health
      Organization for girls and boys aged 5-19. Logistic regression (Enter method)
      determined the overweight/obesity occurrence in a follow-up measurement (2010)
      two years after completion of the controlled intervention was used. RESULTS: Two
      years after the controlled PA intervention had finished, the intervention
      children were less likely to be overweight/obese than the control children
      (2.3%GI vs. 17.1%GC, 6.7%BI vs. 23.4%BC, odds ratio: 0.25; 95% confidence
      interval: 0.12; 0.53; p < 0.001). CONCLUSIONS: The current study indicates
      favourable effects of an everyday school-based PA intervention programme on lower
      overweight/obesity incidence, which was maintained two years after the end of the
      direct involvement of the researchers.

PMID- 23959085
TI  - Assessment of the abuse potential of MDMA in the conditioned place preference
      paradigm: role of CB1 receptors.
AB  - Numerous reports have highlighted the role of the endocannabinoid system in the
      addictive potential of MDMA (3,4-methylenedioxy-methamphetamine). A previous
      report showed that CB1 knockout (KOCB1) mice do not acquire MDMA self
      administration, despite developing conditioned place preference (CPP). This
      contradiction could be due to the particular procedure of place conditioning
      used. The present work compares MDMA-induced CPP in KOCB1 mice using unbiased and
      biased procedures of place conditioning. In the unbiased procedure, MDMA induced
      CPP and reinstatement of the extinguished preference in wild type (WT) mice, but
      not in KOCB1 mice. In contrast, in a biased protocol of CPP, MDMA produced
      preference in both types of mice. The anxiolytic response induced by MDMA in the
      elevated plus maze (EPM) was observed only in KOCB1 mice and may have been
      responsible, at least partially, for the CPP in the biased procedure. A
      neurochemical analysis revealed that KOCB1 mice presented higher striatal DA and
      DOPAC levels in response to MDMA, but no alterations in their levels of monoamine
      transporters. In line with previous self-administration studies, our data suggest
      that CB1 receptors play an important role in the reinforcing effects of MDMA, and
      that the experimental procedure of CPP employed should be taken into account when
      drawing conclusions. 

PMID- 23959086
TI  - Optimal interdependence between networks for the evolution of cooperation.
AB  - Recent research has identified interactions between networks as crucial for the
      outcome of evolutionary games taking place on them. While the consensus is that
      interdependence does promote cooperation by means of organizational complexity
      and enhanced reciprocity that is out of reach on isolated networks, we here
      address the question just how much interdependence there should be. Intuitively,
      one might assume the more the better. However, we show that in fact only an
      intermediate density of sufficiently strong interactions between networks
      warrants an optimal resolution of social dilemmas. This is due to an intricate
      interplay between the heterogeneity that causes an asymmetric strategy flow
      because of the additional links between the networks, and the independent
      formation of cooperative patterns on each individual network. Presented results
      are robust to variations of the strategy updating rule, the topology of
      interdependent networks, and the governing social dilemma, thus suggesting a high
      degree of universality. 

PMID- 23959087
TI  - Catheter-associated bloodstream infection after bowel surgery in patients with
      inflammatory bowel disease.
AB  - PURPOSE: Catheter-associated bloodstream infections (CABSIs) are a leading cause
      of nosocomial infections. The objectives of this study were to establish the
      incidence of CABSIs after bowel surgery and to identify the risk factors.
      METHODS: We reviewed the prospectively collected data of patients who underwent
      abdominal surgery with central venous catheter (CVC) insertion between March,
      2006 and September, 2009. We analyzed all possible variables, including age, sex,
      disease, CVC duration, insertion frequency, CVC site, infliximab, corticosteroid,
      and immunosuppressant administration, preoperative serum albumin level, surgical
      wound class, and emergency surgery. RESULTS: A total of 1261 patients were
      prospectively surveyed. The underlying diseases comprised ulcerative colitis (UC;
      n = 428), Crohn's disease (CD; n = 334), colorectal cancer (CA; n = 344),
      esophageal cancer (ESO; n = 28), gastric cancer (GAST; n = 44), and others (n =
      83). The incidences of CABSI were 6.9/1000 catheter days for UC, 7.4 for CD, 4.3
      for CA, 3.7 for ESO, 3.7 for GAST, and 5.1 for others. CD patients had the
      highest rate of CABSI. The risk factors for CABSI were CD with an odds ratio (OR)
      of 1.63, dirty/infected wound class (OR 3.34), and CVC insertion via the internal
      jugular vein (OR 9.89). CONCLUSION: A high CABSI incidence was found in
      association with CD, especially in dirty/infected surgery. Thus, the use of CVCs
      should be restricted in the presence of these risk factors.

PMID- 23959088
TI  - microRNA-199a-3p, DNMT3A, and aberrant DNA methylation in testicular cancer.
AB  - It was previously demonstrated that miR-199a was downregulated in testicular germ
      cell tumor (TGCT), probably due to hypermethylation of its promoter. Further
      study found that re-expression of miR-199a in testicular cancer cells (NT2) led
      to suppression of cell growth, cancer migration, invasion and metastasis. More
      detailed analyses showed that these properties of miR-199a could be assigned to
      miR-199a-5p, one of its two derivatives. The biological role of the other
      derivative, miR-199a-3p in TGCT, remains largely uncharacterized. In this report,
      we identified DNA (cytosine-5)-methyltransferase 3A (DNMT3A), the de novo
      methyltransferase, as a direct target of miR-199a-3p using a 3'-UTR reporter
      assay. Transient expression of miR-199a-3p in NT2 cells led to decrease, while
      knocking down of miR-199a-3p in a normal human testicular cell line (HT) led to
      elevation, of DNMT3A2 (DNMT3A gene isoform 2) mRNA and protein levels. In
      clinical samples, DNMT3A2 was significantly overexpressed in malignant testicular
      tumor, and the expression of DNMT3A2 was inversely correlated with the expression
      of miR-199a-3p. However, DNMT3A did not affect miR-199a expression in NT2 cells.
      Further characterization of miR-199a-3p revealed that it negatively regulated DNA
      methylation, partly through targeting DNMT3A. Overexpression of miR-199a-3p
      restored the expression of APC and MGMT tumor-suppressor genes in NT2 cells by
      affecting DNA methylation of their promoter regions. Our studies demonstrated the
      deregulation of miR-199a-3p expression in TGCT may provide novel mechanistic
      insights into TGCT carcinogenesis and suggested a potentially therapeutic use of
      synthetic miR-199a-3p oligonucleotides as effective hypomethylating compounds in
      the treatment of TGCT. 

PMID- 23959089
TI  - Clinicopathological and molecular markers associated with prognosis and treatment
      effectiveness of endometrial stromal sarcoma: a retrospective study in China.
AB  - PURPOSE: To evaluate the clinicopathological and immunophenotypic characteristics
      of endometrial stromal sarcoma (ESS) in China. METHODS AND MATERIALS: Seventy-two
      consecutive ESS cases treated between 1995 and 2009 were retrospectively
      reviewed. RESULTS: Sixty-three patients received surgical treatment. Forty-one
      patients underwent pelvic lymphadenectomy. In paraffin-embedded specimens,
      expression of the following molecular markers was detected: CD10 (27/36),
      vimentin (37/38), HHF35 (3/32), S-100 (0/25), desmin (2/29), CD117 (0/23), CD34
      (2/24), alpha-inhibin (0/17), CK (1/34), CD99 (4/9), smooth muscle actin (5/25),
      EMA (0/7), estrogen receptor (13/16) and progesterone receptor (13/16). CD10 and
      vimentin were expressed more frequently in these specimens. Tumor classification,
      CD10 and surgical procedures were significantly associated with disease-free
      survival (DFS). Surgical procedures were significantly associated with overall
      survival (OS). Tumor stage (P = 0.024) and surgical procedure (P = 0.042) were
      found to be significant independent prognostic factors for DFS. No complete or
      partial response was observed among patients who received radiotherapy or
      chemotherapy. CONCLUSIONS: Our results indicate that total hysterectomy with
      bilateral salpingo-oophorectomy followed by pelvic lymphadenectomy is associated
      with an improved treatment outcome. CD10-negative expression may contribute to
      the malignant characteristics and recurrence associated with ESS.

PMID- 23959091
TI  - Evaluation of active camera control systems in gynecological surgery:
      construction, handling, comfort, surgeries and results.
AB  - OBJECTIVE: Surgeon-controlled endoscope leading assistance systems are a novelty
      in endoscopic surgery. These systems were evaluated for their applicability and
      reliability in operative gynecology. In this regard, we evaluated possible
      methods of operation, operative time, setup time, and comfort for the surgeon,
      complications, blood transfusions, length of stay, hemoglobin levels, and
      demographic data. METHODS: Two systems with technically identical camera control
      systems were applied, the SOLOASSISTTM system and the Einstein VisionTM 3D
      system. The arm systems are attached to the operating table and controlled by
      surgeon via a manual control, a remote control or a foot switch. Comfort for the
      surgeon was evaluated using a questionnaire (scale 1-5; 1 "very good", 5 "poor").
      All data were collected prospectively in a database (IBM SPSS Statistics 20) and
      evaluated. RESULTS: One hundred and four patients underwent surgery supported by
      an active control system. In 43 (41 %) cases, oncological interventions were
      performed. Average setup time was 7 (3-30) min. There was a significant learning
      curve regarding the mounting of the system after 20 operations (p = 0.045).
      Overall comfort was rated as "good", divided into control 2.2 (2-4), physical
      effort 2.1 (1-4), picture quality 1.6 (1-3), and overall satisfaction 2.1 (1-4).
      About 75 unwanted camera movements were noticed in 104 surgeries. Complications
      occurred in no case (0 %). CONCLUSION: The application of an active camera
      control system was evaluated to be safe for all gynecological laparoscopies.
      Picture blur is avoided even during prolonged complex procedures. Moreover, the
      assistant is able to support the surgeon with two instruments, with the result
      that the presence of a second assistant is not required for complex
      interventions. Causing only minimal setup time, the examined active control
      systems improve the effectiveness of surgeries. The physical effort required for
      the assistant decreases and, by reducing tiring operations and tremor,
      subsequently, higher precision is reached.

PMID- 23959090
TI  - Expression and localization of maspin in cervical cancer and its role in tumor
      progression and lymphangiogenesis.
AB  - OBJECTIVES: Cervical cancer is the most common malignant tumor in female
      reproductive tract and primarily metastasizes through the lymphatic system that
      will affect prognosis of patients. Maspin, a member of the serine protease
      inhibitors (serpins) super family, has recently been indicated as a tumor
      suppressor in many cancers. In this study, we investigated the clinical
      significance of maspin expression, especially the subcellular location of maspin
      and its functional role in progression and lymphangiogenesis, in cervical
      squamous cell carcinoma. METHODS: Labelled streptavidin biotin method (LSAB) was
      used to determine cytoplasmic and nuclear maspin expressions, respectively, in 13
      cases of normal cervix, 15 cases of cervical intraepithelial neoplasia grade 3
      (CIN3), 62 cases of squamous cell carcinoma (SCC) of the uterine cervix, and 13
      cases of pelvic lymphatic nodes which were all positive lymphatic nodes in our
      selected cancer cases. LSAB is also used to detect podoplanin which is used for
      counting density of lymphatic microvessels (LMVD). The clinical significance of
      subcellular maspin expression and the relationship between maspin expression and
      LMVD in cervical cancer are analyzed. RESULTS: Both cytoplasmic and nuclear
      maspin expressions in SCC were significantly weaker than those of normal cervix
      and CIN3. Nuclear maspin expression showed a peak in CIN3 and then dropped in
      SCC. Declined maspin expression was correlated with later clinical stage,
      increased LMVD, and lymphatic metastasis. CONCLUSIONS: Our results suggest that
      subcellular location of maspin expression is a potential predictive factor in
      tumor progression and in patients' prognosis of cervical cancer, and maspin plays
      a suppression role in lymphangiogenesis and metastasis.

PMID- 23959092
TI  - Patient satisfaction with childbirth after external cephalic version.
AB  - PURPOSE: To assess acceptance and impact of external cephalic version (ECV) for
      breech presentation at term on maternal satisfaction with childbirth. METHODS:
      Retrospective study on n = 131 women with breech presentation comparing maternal
      satisfaction after ECV and consecutive childbirth (n = 66; 50.4% of these
      successful attempts in n = 33; 50%) against the group without ECV and primary
      caesarean section (CS) (n = 65; 49.6%) instead using a questionnaire. RESULTS:
      Women with successful ECV tolerated side effects of the intervention better than
      after unsuccessful ECV (pain, tocolytics, mental and physical state, for all p <
      0.001). They were not more satisfied with childbirth than women who experienced
      an unsuccessful ECV (p = 0.37). However, they would undergo the procedure again
      (p = 0.003) and would recommend it to other women (p < 0.001). Only women with
      spontaneous vaginal deliveries after successful version were more satisfied with
      childbirth than women with planned CS (p = 0.05). Women with version attempts
      tend to perceive childbirth as being less problematic with fewer complications
      (9.5 vs. 19%, p = 0.12). Unsuccessful ECVs had no negative impact on satisfaction
      with childbirth (p = 0.072). CONCLUSION: Attempting ECV seems to be an option for
      increasing the rate of vaginal births with breech presentation without negative
      impact on maternal satisfaction regarding consecutive childbirth.

PMID- 23959093
TI  - Anesthetic considerations for high order cesarean sections: a prospective cohort
      study.
AB  - BACKGROUND: In a previous retrospective study we demonstrated that perioperative
      complications occurred in a minority of high order repeat cesarean sections (HOR
      C/S). In this prospective study we compared the incidence of complications in
      patients who have had four or more cesarean sections to those that had three or
      less. METHODS: This was a prospective, observational cohort study of parturients
      undergoing C/S at a single tertiary care hospital over a 1 year period. We
      compared the incidence of conversion from regional to general anesthesia,
      duration of surgery and incidence of major blood loss in HOR-C/S to control.
      RESULTS: We studied a total of 831 parturients, 129 underwent HOR-C/S. The
      incidence of conversion from regional to general anesthesia was similar in both
      groups (RR = 0.97, 95% CI 0.2, 4.3). The median duration of surgery was 40 min
      (range 10-145 min) in the HOR-C/S group and 30 min (range 10-150 min) in the
      control group (p < 0.001). The incidence of prolonged surgery was increased in
      the HOR-C/S group (RR = 3.6, 95% CI 2.4, 5.4). The incidence of intraoperative
      blood transfusion was higher in the HOR-C/S group (RR = 3.4, 95% CI 1.1, 10.2).
      CONCLUSIONS: Patients who have HOR-C/S are more likely to have prolonged surgery
      and require blood transfusion than controls. However, in our population, this was
      not associated with an increased incidence of conversion from regional to general
      anesthesia. Provided causes of severe hemorrhage such as abnormal placentation
      have been ruled out, HOR-C/S is not an absolute contraindication to regional
      block.

PMID- 23959094
TI  - Letter to the editor referring to the manuscript entitled: "Increasing fear of
      adverse effects drops intention to vaccinate after the introduction of
      prophylactic HPV vaccine" reported by Sotiriadis et al. (Arch Gynecol Obstet.
      2012 Jun;285(6):1719-24).

PMID- 23959095
TI  - Epidural neostigmine and clonidine improves the quality of combined spinal
      epidural analgesia in labour: a randomised, double-blind controlled trial.
AB  - BACKGROUND: In labour analgesia, the combination of epidural clonidine and
      neostigmine as adjuvants to local anaesthetics and opioids is under investigation
      to provide a longer duration of initial spinal analgesia with local anaesthetics
      and/or opioids. OBJECTIVES: To evaluate the quality of analgesia with epidural
      neostigmine and clonidine, added to initial spinal analgesia, and to test the
      hypothesis that the incidence of breakthrough pain could be reduced and patient
      satisfaction improved. DESIGN: Randomised double-blind controlled trial. SETTING:
      University Hospital of Leuven in Belgium. PARTICIPANTS: One hundred healthy, term
      (>=37 weeks) parturients. INTERVENTION: All patients received initial spinal
      analgesia with ropivacaine and sufentanil. Fifteen minutes after spinal
      injection, 10 ml of a solution containing neostigmine 500 MUg and clonidine 75
      MUg, or 10 ml physiological saline alone was injected epidurally. Patient
      controlled analgesia with ropivacaine and sufentanil was then made available.
      MAIN OUTCOME MEASURES: The incidence of breakthrough pain, patient satisfaction
      and hourly ropivacaine use. RESULTS: Ropivacaine use decreased significantly by
      32.6% in the neostigmine/clonidine (NC) group [11.6 +/- 4.2 vs. 17.2 +/- 5.3 mg h
      in the NC group and placebo (P) group, respectively] and a significant difference
      in breakthrough pain was noted; only 3% in group NC had breakthrough pain
      compared with 36% in group P. Patient satisfaction was better after 1 h in group
      NC compared with group P (P <0.05) but not different after 24 h (visual analogue
      scale score 97 +/- 5 vs. 88 +/- 11 mm after 1 h; 92 +/- 10 vs. 90 +/- 14 mm after
      24 h). CONCLUSION: The administration of epidural clonidine and neostigmine as
      adjuvants, following spinal injection of local anaesthetic, improves the quality
      of analgesia with less ropivacaine consumption, higher patient satisfaction 1 h
      after administration and a decrease in breakthrough pain compared to standard
      combined spinal and epidural analgesia and patient-controlled epidural analgesia
      with ropivacaine and sufentanil.

PMID- 23959096
TI  - Reply to: Wound infusion of bupivacaine following radical retropubic
      prostatectomy.

PMID- 23959097
TI  - Considerations for normalization of DNA methylation data by Illumina 450K
      BeadChip assay in population studies.
AB  - Analysis of epigenetic mechanisms, particularly DNA methylation, is of increasing
      interest for epidemiologic studies examining disease etiology and impacts of
      environmental exposures. The Infinium HumanMethylation450 BeadChip((r)) (450K),
      which interrogates over 480,000 CpG sites and is relatively cost effective, has
      become a popular tool to characterize the DNA methylome. For large-scale studies,
      minimizing technical variability and potential bias is paramount. The goal of
      this paper was to evaluate the performance of several existing and novel color
      channel normalizations designed to reduce technical variability and batch effects
      in 450K analysis from a large population study. Comparative assessment of 10
      normalization procedures included the GenomeStudio((r)) Illumina procedure, the
      lumi smooth quantile approach, and the newly proposed All Sample Mean
      Normalization (ASMN). We also examined the performance of normalizations in
      combination with correction for the two types of Infinium chemistry utilized on
      the 450K array. We observed that the performance of the GenomeStudio((r))
      normalization procedure was highly variable and dependent on the quality of the
      first sample analyzed in an experiment, which is used as a reference in this
      procedure. While the lumi normalization was able to decrease batch variability,
      it increased variation among technical replicates, potentially reducing
      biologically meaningful findings. The proposed ASMN procedure performed
      consistently well, both at reducing batch effects and improving replicate
      comparability. In summary, the ASMN procedure can improve existing color channel
      normalization, especially for large epidemiologic studies, and can be
      successfully implemented to enhance a 450K DNA methylation data pipeline.

PMID- 23959099
TI  - Synthesis, linear and nonlinear optical properties of phosphonato-substituted
      bithiophenes derived from 2,2'-biphenol.
AB  - Two new series of phosphonato-substituted bithiophenes, BpP(X)(C4H2S)2H and
      BpP(X)(C4H2S)2P(X)Bp (Bp = 2,2'-C12H8O2, X = O, S, Se), have been synthesized and
      characterized using linear absorption and emission spectra, and third-order
      nonlinear absorption measurements at 430 nm with 27 ps laser pulses. The
      compounds were synthesized in three steps: (1) reacting lithiated bithiophene
      with (Et2N)2PCl; (2) reacting the product from the first step with biphenol; and
      (3) reacting the product from the second step with the appropriate chalcogen. The
      X-ray crystal structures of two of the compounds, BpP(O)(C4H2S)2P(O)Bp and
      BpP(Se)(C4H2S)2P(Se)Bp, are reported and show a number of intermolecular pi-pi
      interactions. The linear absorption spectra, emission spectra, and emission
      quantum yields show distinct trends with respect to the chalcogen and the number
      of phosphorus substituents attached to the 2,2'-bithiophene ring. The compounds
      show emission maxima at wavelengths ranging from 380-400 nm and, BpP(S)(C4H2S)2H
      shows a 23-fold increase in fluorescence quantum yield relative to that of 2,2'
      bithiophene. Fluorescence lifetimes and radiative and non-radiative decay rate
      constants for the first singlet excited state have been extracted from the
      quantum yields using time-dependent DFT calculations. Nonlinear transmission
      measurements indicate that all of the compounds show nonlinear absorption at 430
      nm with 27 ps laser pulses in spite of their low solubilities. Notably, the
      nonlinear absorption threshold of a 0.16 mol L(-1) CH2Cl2 solution of
      BpP(Se)(C4H2S)2H is 0.9 J cm(-2). The excellent emission quantum yields and good
      nonlinear absorptions make these compounds promising candidates for optical power
      limiting applications and as host materials for violet-blue organic light
      emitting diodes. 

PMID- 23959098
TI  - Anti-apoptotic phenotypes of cholestan-3beta,5alpha,6beta-triol-resistant human
      cholangiocytes: characteristics contributing to the genesis of
      cholangiocarcinoma.
AB  - The oxysterols cholestan-3beta,5alpha,6beta-triol (Triol) and 3-keto-cholest-4
      ene (3K4) are increased in Opisthorchis viverrini-associated hamster
      cholangiocarcinoma and induce DNA damage and apoptosis via a mitochondria
      dependent mechanism in MMNK-1 human cholangiocytes. Based on these observations,
      we hypothesized that chronic exposure of cholangiocytes to these pathogenic
      oxysterols may allow a growth advantage to a subset of these cells through
      selection for resistance to apoptosis, thereby contributing to
      cholangiocarcinogenesis. To test this hypothesis, we cultured MMNK-1 cells long
      term in the presence of Triol. Alteration in survival and apoptotic factors of
      Triol-exposed cells were examined. Cells cultured long-term in the presence of
      Triol were resistant to H2O2-induced apoptosis, and demonstrated an increase in
      the phosphorylation of p38-alpha, CREB, ERK1/2 and c-Jun. Elevations in the ratio
      of Bcl-2/Bax and in the protein levels of anti-apoptotic factors including cIAP2,
      clusterin, and survivin were detected. These results show that long-term exposure
      of MNNK-1 cells to low doses of Triol selects for kinase-signaling molecules
      which regulate resistance to apoptosis and thereby enhance cell survival. Clonal
      expansion of such apoptosis-resistant cells may contribute to the genesis of
      cholangiocarcinoma. 

PMID- 23959100
TI  - The use of chemical occurrence data at European vs. national level in dietary
      exposure assessments: a methodological study.
AB  - A typical EFSA approach to assess dietary exposure is to combine data from
      national consumption surveys with chemical occurrence data that have been pooled
      across the EU Member States (pooled approach). This approach was compared to the
      case where occurrence data were stratified by country and used for food
      categories where national data were abundant (semi-pooled approach), using
      cadmium as a case study. Some differences in estimated dietary exposure were
      observed between the pooled and semi-pooled approach. They were explained by
      differences, between the national and the European occurrence data, with respect
      to (1) contamination values and (2) sample proportions of food items classified
      in the food categories the assessment was based on. The latter aspect highlighted
      the sensitivity of the approach of directly aggregating monitoring data into food
      categories. Both the pooled and semi-pooled approach tended to be conservative
      relative to approaches used at national level. This appears to be attributed to
      differences in the way the available occurrence data is aggregated. Refinement of
      the studied methodologies would include a better separation of the food items
      with high concentration from those with low concentration. 

PMID- 23959101
TI  - Daidzein causes cytochrome c-mediated apoptosis via the Bcl-2 family in human
      hepatic cancer cells.
AB  - Daidzein, which belongs to the group of isoflavones from soybeans, has been
      extensively researched prostate, cervix, brain, breast, and colon cancer cell
      lines. However, daidzein has not been thoroughly investigated in human hepatic
      cancer cells; therefore, we investigated whether it inhibits hepatic cancer cell
      growth. Decreased cell proliferation was measured in daidzein-treated hepatic
      cancer cells (SK-HEP-1) upon real-time cell electronic sensing analysis however,
      it was not affected on normal human hepatocytes (Chang). Daidzein-induced
      apoptosis was demonstrated by comet and TUNEL assay. Moreover, we conducted two
      dimensional electrophoresis to study the mechanism of daidzein-induced apoptosis
      in daidzein-treated SK-HEP-1 cells. Expression of peroxiredoxin-3 (Prdx-3), which
      modulates redox homeostasis of cells, was increased in protein analysis.
      Additionally, we measured the levels of reactive oxygen species and it was
      decreased in daidzein-treated SKHEP-1 cells. Daidzein-induced apoptosis in SK-HEP
      1 cells was also associated with the up-regulation of Bak and down-regulation of
      Bcl-2 and Bcl-xL proteins. Moreover, daidzein treatment increased in the release
      of mitochondrial cytochrome c and activation of APAF-1, caspase 9 and caspase 3.
      Overall, these result indicate that daidzein is a potent inducer of apoptosis in
      hepatic cancer cells via mitochondrial pathway. 

PMID- 23959102
TI  - Physico-chemical characterization-based safety evaluation of nanocalcium.
AB  - Nano- and microcalcium provided from the KFDA were compared in terms of physico
      chemical properties. Calcium samples were tested using EF-TEM and X-ray
      diffractometry to check for size/morphology and crystal formation, respectively.
      Two samples of nano- and microcalcium were selected for further evaluation by FE
      SEM, DLS (nano-size, 200-500nm; agglomerate, >5 MUm; micro-size, 1.5-30 MUm), and
      electron spin resonance. Both samples were heterogeneous in size, existed as
      single crystal and aggregated form, and did not generate reactive oxygen species.
      The specific surface area of nano- and microcalcium measured by N2 Brunauere
      Emmette Teller method was 12.90+/-0.27 m(2)/g and 1.12+/-0.19 m(2)/g,
      respectively. Inductively coupled plasma optical emission spectrometry analysis
      revealed the release of 2-3 times more calcium ion from nano- compared to
      microcalcium at pH 5 and 7. Genotoxicity and acute single-dose and repeated-dose
      14-day oral toxicity testing in SD rats performed to evaluate the safety of
      nanocalcium did not reveal toxicity. However, long-term monitoring will be
      required for an unequivocal conclusion. A nanocalcium dose of 1 g/kg is
      recommended as the maximum dose for repeated dose 13-week oral toxicity. Further
      studies could provide details of toxicity of nanocalcium on the repeated dose 13
      week oral toxicity test.

PMID- 23959103
TI  - Matrix-derived combination effect and risk assessment for estragole from basil
      containing plant food supplements (PFS).
AB  - Basil-containing plant food supplements (PFS) can contain estragole which can be
      metabolised into a genotoxic and carcinogenic 1'-sulfoxymetabolite. This study
      describes the inhibition of sulfotransferase (SULT)-mediated bioactivation of
      estragole by compounds present in basil-containing PFS. Results reveal that PFS
      consisting of powdered basil material contain other compounds with considerable
      in vitro SULT-inhibiting activity, whereas the presence of such compounds in PFS
      consisting of basil essential oil was limited. The inhibitor in powdered basil
      PFS was identified as nevadensin. Physiologically based kinetic (PBK) modeling
      was performed to elucidate if the observed inhibitory effects can occur in vivo.
      Subsequently, risk assessment was performed using the Margin of Exposure (MOE)
      approach. Results suggest that the consequences of the in vivo matrix-derived
      combination effect are significant when estragole would be tested in rodent
      bioassays with nevadensin at ratios detected in PFS, thereby increasing MOE
      values. However, matrix-derived combination effects may be limited at lower dose
      levels, indicating that the importance of matrix-derived combination effects for
      risk assessment of individual compounds should be done on a case-by-case basis
      considering dose-dependent effects. Furthermore, this study illustrates how PBK
      modeling can be used in risk assessment of PFS, contributing to further reduction
      in the use of experimental animals. 

PMID- 23959104
TI  - Endogenous allergens and compositional analysis in the allergenicity assessment
      of genetically modified plants.
AB  - Allergenicity assessment of genetically modified (GM) plants is one of the key
      pillars in the safety assessment process of these products. As part of this
      evaluation, one of the concerns is to assess that unintended effects (e.g. over
      expression of endogenous allergens) relevant for the food safety have not
      occurred due to the genetic modification. Novel technologies are now available
      and could be used as complementary and/or alternative methods to those based on
      human sera for the assessment of endogenous allergenicity. In view of these
      developments and as a step forward in the allergenicity assessment of GM plants,
      it is recommended that known endogenous allergens are included in the
      compositional analysis as additional parameters to be measured. 

PMID- 23959105
TI  - Are typical human serum BPA concentrations measurable and sufficient to be
      estrogenic in the general population?
AB  - Mammalian estrogen receptors modulate many physiological processes. Chemicals
      with structural features similar to estrogens can interact with estrogen
      receptors to produce biological effects similar to those caused by endogenous
      estrogens in the body. Bisphenol A (BPA) is a structural analogue of estrogen
      that binds to estrogen receptors. Exposure to BPA in humans is virtually
      ubiquitous in industrialized societies, but BPA is rapidly detoxified by
      metabolism and does not accumulate in the body. Whether or not serum
      concentrations of BPA in humans are sufficiently high to disrupt normal estrogen
      related biology is the subject of intense political and scientific debate. Here
      we show a convergence of robust methods for measuring or calculating serum
      concentrations of BPA in humans from 93 published studies of more than 30,000
      individuals in 19 countries across all life stages. Typical serum BPA
      concentrations are orders of magnitude lower than levels measurable by modern
      analytical methods and below concentrations required to occupy more than 0.0009%
      of Type II Estrogen Binding Sites, GPR30, ERalpha or ERbeta receptors.
      Occupancies would be higher, but <=0.04%, for the highest affinity receptor,
      ERRgamma. Our results show limited or no potential for estrogenicity in humans,
      and question reports of measurable BPA in human serum.

PMID- 23959106
TI  - Hydroxyl radical induced by lipid in Maillard reaction model system promotes diet
      derived N(epsilon)-carboxymethyllysine formation.
AB  - N(epsilon)-carboxymethyllysine (CML) is commonly found in food, and is considered
      as a potential hazard to human health. However, the effect of lipids on CML
      formation in Maillard reaction is still not clarified. In this study, the content
      of diet-derived CML and its key intermediates, epsilon-fructoselysine (FL) and
      glyoxal (GO), is determined with high performance liquid chromatography mass
      spectrum (HPLC-MS) in model system containing lipid compounds. According to the
      results, hydroxyl radical (OH) induced by Fenton reagent can promote the three
      pathways of CML formation. Moreover, in the Maillard reaction system, linoleic
      acid (Lin), oleic acid (Ole) and glycerol trioleate (Tri) can induce more OH.,
      which promotes CML formation. Their level of promoting CML formation is in the
      order of Ole>Lin>Tri. On the contrary, glycerol (Gly) can scavenge OH., which
      inhibit the CML formation. Finally, it is proved that FL content and GO content
      decreases with heating time in model system, while CML content increases with
      heating time. Thus, it is concluded that in the Maillard reaction system lipids
      can induce more OH., which promotes the conversion from FL and GO to CML. Our
      research may contribute to the development of inhibitory methods for diet-derived
      CML by scavenging OH..

PMID- 23959107
TI  - The heparan sulfate editing enzyme Sulf1 plays a novel role in zebrafish VegfA
      mediated arterial venous identity.
AB  - Arterial and venous specification is critical for establishing and maintaining a
      functioning vascular system, and defects in key arteriovenous signaling pathways
      including VEGF (vascular endothelial growth factor) lead to congenital
      arteriopathies. The activities of VEGF, are in part controlled by heparan sulfate
      (HS) proteoglycans, significant components of the endothelial glycocalyx. The
      level of 6-O sulfation on HS polysaccharide chains, that mediate the interaction
      between HS and VEGFA, is edited at the cell surface by the enzyme SULF1. We
      investigated the role of sulf1 in vascular development. In zebrafish sulf1 is
      expressed in the head and tail vasculature, corresponding spatially and
      temporally with vascular development. Targeted knockdown of sulf1 by antisense
      morpholinos resulted in severe vascular patterning and maturation defects. 93 %
      of sulf1 morphants show dysmorphogenesis in arterial development leading to
      occlusion of the distal aorta and lack of axial and cranial circulation. Co
      injection of vegfa165 mRNA rescued circulatory defects. While the genes affecting
      haematopoiesis are unchanged, expression of several arterial markers downstream
      of VegfA signalling such as notch and ephrinB2 are severely reduced in the dorsal
      aorta, with a concomitant increase in expression of the venous markers flt4 in
      the dorsal aorta of the morphants. Furthermore, in vitro, lack of SULF1
      expression downregulates VEGFA-mediated arterial marker expression, confirming
      that Sulf1 mediates arterial specification by regulating VegfA165 activity. This
      study provides the first in vivo evidence for the integral role of the
      endothelial glycocalyx in specifying arterial-venous identity, vascular
      patterning and arterial integrity, and will help to better understand congenital
      arteriopathies.

PMID- 23959108
TI  - Amyotrophic lateral sclerosis and spinocerebellar ataxia type 2 in a family with
      full CAG repeat expansions of ATXN2.
AB  - IMPORTANCE: A family with coexistence of spinocerebellar ataxia type 2 and
      amyotrophic lateral sclerosis (ALS) is described. OBSERVATIONS: Intermediate or
      full CAG repeat expansions of ATXN2 are associated with ALS. However, no
      coexistence of spinocerebellar ataxia type 2 and ALS in a family has been
      reported in the literature.We describe a 47-year-old woman with an 11-year
      history of ataxia and her paternal uncle with ALS who were evaluated at Columbia
      University Medical Center since July 2006. Both our patient with ataxia and her
      uncle with ALS have full pathological CAG repeat expansions of ATXN2. CONCLUSIONS
      AND RELEVANCE: The diverse clinical phenotypes of ATXN2 CAG expansions and their
      coexistence in a single family are highlighted. A clinician should consider the
      diagnosis of spinocerebellar ataxia type 2 when encountering a patient with
      ataxia and a family history of ALS.

PMID- 23959109
TI  - A "nano-windmill" driven by a flux of water vapour: a comparison to the rotating
      ATPase.
AB  - We measure the frequency of collective molecular precession as a function of
      temperature in the ferroelectric liquid crystalline monolayer at the water-air
      interface. This movement is driven by the unidirectional flux of evaporating
      water molecules. The collective rotation in the monolayer with angular velocities
      omega ~ 1 s(-1) (at T = 312 K) to 10(-2) s(-1) (at T = 285.8 K) is 9 to 14 orders
      of magnitude slower than rotation of a single molecule (typically omega ~ 10(9)
      to 10(12) s(-1)). The angular velocity reaches 0 upon approach to the two
      dimensional liquid-to-solid transition in the monolayer at T = 285.8 K. We
      estimate the rotational viscosity, gamma1, in the monolayer and the torque,
      Gamma, driving this rotation. The torque per molecule equals Gamma = 5.7 * 10(-8)
      pN nm at 310 K (gamma1 = 0.081 Pa s, omega = 0.87 s(-1)). The energy generated
      during one turn of the molecule at the same temperature is W = 3.5 * 10(-28) J.
      Surprisingly, although this energy is 7 orders of magnitude smaller than the
      thermal energy, kBT (310 K) = 4.3 * 10(-21) J, the rotation is very stable. The
      potential of the studied effect lies in the collective motion of many (>10(12))
      "nano-windmills" acting "in concerto" at the scale of millimetres. Therefore,
      such systems are candidates for construction of artificial molecular engines,
      despite the small energy density per molecular volume (5 orders of magnitude
      smaller than for a single ATPase).

PMID- 23959110
TI  - T-cell subpopulations alphabeta and gammadelta in cord blood of very preterm
      infants: the influence of intrauterine infection.
AB  - Preterm infants are very susceptible to infections. Immune response mechanisms in
      this group of patients and factors that influence cord blood mononuclear cell
      populations remain poorly understood and are considered insufficient. However,
      competent immune functions of the cord blood mononuclear cells are also
      described. The aim of this work was to evaluate the T-cell population (CD3+) with
      its subpopulations bearing T-cell receptor (TCR) alphabeta or TCR gammadelta in
      the cord blood of preterm infants born before 32 weeks of gestation by mothers
      with or without an intrauterine infection. Being a pilot study, it also aimed at
      feasibility check and assessment of an expected effect size. The cord blood
      samples of 46 infants age were subjected to direct immunofluorescent staining
      with monoclonal antibodies and then analyzed by flow cytometry. The percentage of
      CD3+ cells in neonates born by mothers with diagnosis of intrauterine infection
      was significantly lower than in neonates born by mothers without infection (p =
      0.005; Mann-Whitney U test). The number of cells did not differ between groups.
      Infection present in the mother did not have an influence on the TCR alphabeta or
      TCR gammadelta subpopulations. Our study contributes to a better understanding of
      preterm infants' immune mechanisms, and sets the stage for further
      investigations.

PMID- 23959111
TI  - Flow cytometric analysis of CD133- and EpCAM-positive cells in the peripheral
      blood of patients with lung cancer.
AB  - Lung tumors are characterized by their high metastatic potential, which is the
      main cause of therapeutic failure. However, the exact cellular origin of
      metastasis remains unknown. Since the introduction of the cancer stem cell
      theory, lung cancer stem cells (LCSCs) have been thought to represent metastasis
      founding cells. The current study aimed to evaluate whether LCSCs could be found
      in the circulation. Expression of the stem cell markers CD133 and EpCAM was
      confirmed in tumor and normal lung tissue by flow cytometry. Then, this technique
      was further used to investigate the expression of CD133 and EpCAM in the
      peripheral blood of 41 patients with primary lung cancer. Putative LCSCs
      (CD133?EpCAM?) were present in 6/7 tumor samples, and CD133?EpCAM? cells were
      identified in the blood samples of 15 patients at a median level of 40/ml of
      blood. EpCAM? cells were detected in 60 % of the patients, and the number of
      these cells was higher in patients with adenocarcinoma than patients with
      squamous cell carcinoma and was also higher in patients with less advanced
      disease. Moreover, the frequency of this subpopulation significantly correlated
      with the circulating level of SSEA-4? cells. Additionally, CD133?EpCAM- cells
      were found in 87 % of the patients, and the numbers of these cells were
      significantly higher in patients with distant metastases and correlated with
      disease stage. This study confirmed the presence of an LCSC subpopulation with a
      CD133?EpCAM? phenotype in the tumors and blood of patients with lung cancer, and
      these results suggest an important role for CD133 and EpCAM in lung cancer
      progression and their potential application as novel biomarkers of the disease.

PMID- 23959112
TI  - Lobular breast cancer: pathology, biology, and options for clinical intervention.
AB  - Lobular carcinoma is a breast cancer subtype comprising approximately 15 % of all
      breast cancer cases. Clinical diagnosis of this subtype is difficult due to a
      characteristic growth pattern that inhibits detection using palpation or standard
      X-ray mammography. While clinical intervention based on hormone antagonists has
      proven an effective strategy, hormone receptor negative or nonresponsive disease
      cannot be treated successfully, indicating the need for alternative curative
      approaches. In contrast to its well-defined histopathological characteristics
      that were first recognized a century ago, the surface of the underlying biology
      has only recently been scratched. Progress was made in understanding the biology
      of the disease, which will hopefully have its impact on future treatment
      modalities and initiate development of novel intervention strategies. Here, we
      review the pathological and molecular features of lobular breast cancer and
      report on the currently known mechanisms that control disease development and
      progression. Finally we will reflect on past, present, and future treatment
      options.

PMID- 23959114
TI  - Probiotic dosing of Ruminococcus flavefaciens affects rumen microbiome structure
      and function in reindeer.
AB  - Highly cellulolytic bacterial species such as Ruminococcus flavefaciens are
      regarded essential for the microbial breakdown of cellulose in the rumen. We have
      investigated the effect of ruminal dosing of R. flavefaciens strain 8/94-32
      during realimentation of starved reindeer (males, n = 3). Microbiome function
      measured as in situ digestion of cellulose and food pellets (percent DMD; dry
      matter disappearance) decreased after probiotic dosing. Microbial community
      analyses (>100,000 16S rDNA gene sequences for 27 samples) demonstrated that
      ruminal dosing influenced the microbiome structure; reflected by increased
      phylogenetic distances from background samples (unweighted UniFrac analysis) and
      reduced species diversity and evenness. Despite the inability to detect strain
      8/94-32 post-dosing, the relative abundance of its affiliate family
      Ruminococcaceae remained consistent throughout the trial, whilst a dominant peak
      in the genus Prevotella and decline in uncharacterized Bacteroidetes (uBacNR)
      were observed in treatment samples. No clear relationships were observed between
      the relative abundance of Ruminococcaceae, Prevotella and uBacNR with cellulose
      DMD; however, Prevotella (negative) and uBacNR (positive) exhibited relationships
      with pellet DMD. These unexpected effects of ruminal dosing of a cellulolytic
      bacterium on digestibility are relevant for other studies on rumen manipulation.

PMID- 23959115
TI  - Resource use of soilborne Streptomyces varies with location, phylogeny, and
      nitrogen amendment.
AB  - In this study, we explore variation in resource use among Streptomyces in prairie
      soils. Resource use patterns were highly variable among Streptomyces isolates and
      were significantly related to location, phylogeny, and nitrogen (N) amendment
      history. Streptomyces populations from soils less than 1 m apart differed
      significantly in their ability to use resources, indicating that drivers of
      resource use phenotypes in soil are highly localized. Variation in resource use
      within Streptomyces genetic groups was significantly associated with the location
      from which Streptomyces were isolated, suggesting that resource use is adapted to
      local environments. Streptomyces from soils under long-term N amendment used
      fewer resources and grew less efficiently than those from non-amended soils,
      demonstrating that N amendment selects for Streptomyces with more limited
      catabolic capacities. Finally, resource use among Streptomyces populations was
      correlated with soil carbon content and Streptomyces population densities. We
      hypothesize that variation in resource use among Streptomyces reflects adaptation
      to local resource availability and competitive species interactions in soil and
      that N amendments alter selection for resource use phenotypes.

PMID- 23959116
TI  - L/N-type calcium channel blocker cilnidipine added to renin-angiotensin
      inhibition improves ambulatory blood pressure profile and suppresses cardiac
      hypertrophy in hypertension with chronic kidney disease.
AB  - Ambulatory blood pressure (BP) and heart rate (HR) profile are proposed to be
      related to renal deterioration and cardiovascular complication in hypertension
      and chronic kidney disease (CKD). In this study, we examined the beneficial
      effects cilnidipine, a unique L/N-type calcium channel blocker (CCB), in addition
      to renin-angiotensin system inhibitors, on ambulatory BP and HR profile, as well
      as cardiorenal function in hypertensive CKD patients. Forty-five patients were
      randomly assigned to the cilnidipine replacement group (n = 21) or the control
      CCBs group (n = 24) during a 24-week active treatment period. Although clinical
      BP values were similar in the cilnidipine and control CCBs groups after the
      treatment period, the results of ambulatory BP monitoring showed that the 24-h
      and daytime systolic BP levels in the cilnidipine group were significantly lower
      compared with the control group after the study. Furthermore, the left
      ventricular mass index (LVMI) was significantly decreased in the cilnidipine
      group compared to the control group after the study (LVMI, 135.3 +/- 26.4 versus
      181.2 +/- 88.4, p = 0.031), with a significant difference in the changes in the
      LVMI between the cilnidipine and control groups (change in LVMI, -12.4 +/- 23.7
      versus 26.2 +/- 64.4, p = 0.007). These results indicate that cilnidipine is
      beneficial for the suppression of pathological cardiac remodeling, at least
      partly, via a superior improving effect on ambulatory BP profile compared with
      control CCBs in hypertensive CKD patients. 

PMID- 23959117
TI  - Oximes: inhibitors of human recombinant acetylcholinesterase. A structure
      activity relationship (SAR) study.
AB  - Acetylcholinesterase (AChE) reactivators were developed for the treatment of
      organophosphate intoxication. Standard care involves the use of anticonvulsants
      (e.g., diazepam), parasympatolytics (e.g., atropine) and oximes that restore AChE
      activity. However, oximes also bind to the active site of AChE, simultaneously
      acting as reversible inhibitors. The goal of the present study is to determine
      how oxime structure influences the inhibition of human recombinant AChE (hrAChE).
      Therefore, 24 structurally different oximes were tested and the results compared
      to the previous eel AChE (EeAChE) experiments. Structural factors that were
      tested included the number of pyridinium rings, the length and structural
      features of the linker, and the number and position of the oxime group on the
      pyridinium ring. 

PMID- 23959118
TI  - Bioinformatic prediction of gene functions regulated by quorum sensing in the
      bioleaching bacterium Acidithiobacillus ferrooxidans.
AB  - The biomining bacterium Acidithiobacillus ferrooxidans oxidizes sulfide ores and
      promotes metal solubilization. The efficiency of this process depends on the
      attachment of cells to surfaces, a process regulated by quorum sensing (QS) cell
      to-cell signalling in many Gram-negative bacteria. At. ferrooxidans has a
      functional QS system and the presence of AHLs enhances its attachment to pyrite.
      However, direct targets of the QS transcription factor AfeR remain unknown. In
      this study, a bioinformatic approach was used to infer possible AfeR direct
      targets based on the particular palindromic features of the AfeR binding site. A
      set of Hidden Markov Models designed to maintain palindromic regions and vary non
      palindromic regions was used to screen for putative binding sites. By annotating
      the context of each predicted binding site (PBS), we classified them according to
      their positional coherence relative to other putative genomic structures such as
      start codons, RNA polymerase promoter elements and intergenic regions. We further
      used the Multiple EM for Motif Elicitation algorithm (MEME) to further filter out
      low homology PBSs. In summary, 75 target-genes were identified, 34 of which have
      a higher confidence level. Among the identified genes, we found afeR itself, zwf,
      genes encoding glycosyltransferase activities, metallo-beta lactamases, and
      active transport-related proteins. Glycosyltransferases and Zwf (Glucose 6
      phosphate-1-dehydrogenase) might be directly involved in polysaccharide
      biosynthesis and attachment to minerals by At. ferrooxidans cells during the
      bioleaching process. 

PMID- 23959120
TI  - The association of IFI27 expression and fatigue intensification during localized
      radiation therapy: implication of a para-inflammatory bystander response.
AB  - The mechanisms behind fatigue intensification during cancer therapy remain
      elusive. The interferon alpha-inducible protein 27 (IFI27) was the most up
      regulated gene based on our previous microarray data in fatigued men with non
      metastatic prostate cancer receiving localized external beam radiation therapy
      (EBRT). The purpose of this study was to confirm the IFI27 up-regulation and
      determine its association with fatigue intensification during EBRT. Peripheral
      blood samples and fatigue scores were collected at three time points--prior to
      EBRT, at midpoint, and at completion of EBRT. Confirmatory quantitative real time
      polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA)
      were utilized to verify the microarray results. Subjects were a total of 40
      Caucasian men with prostate cancer; 20 scheduled for EBRT (65.6 +/- 7.5 years
      old), and 20 on active surveillance as controls (62.8 +/- 6.1 years old).
      Significant IFI27 expression overtime during EBRT was confirmed by qPCR (p <
      0.5), which correlated with fatigue scores during EBRT (R = -0.90, p = 0.006).
      Alterations in mechanisms associated with immune response and mitochondrial
      function that explain the up-regulation of IFI27 may provide an understanding of
      the pathways related to the intensification of fatigue during localized radiation
      therapy.

PMID- 23959119
TI  - ACE inhibition with captopril retards the development of signs of
      neurodegeneration in an animal model of Alzheimer's disease.
AB  - Increased generation of reactive oxygen species (ROS) is a significant
      pathological feature in the brains of patients with Alzheimer's disease (AD).
      Experimental evidence indicates that inhibition of brain ROS could be beneficial
      in slowing the neurodegenerative process triggered by amyloid-beta (Abeta)
      aggregates. The angiotensin II AT1 receptor is a significant source of brain ROS,
      and AD patients have an increased brain angiotensin-converting enzyme (ACE)
      level, which could account for an excessive angiotensin-dependent AT1-induced ROS
      generation. Therefore, we analyzed the impact of ACE inhibition on signs of
      neurodegeneration of aged Tg2576 mice as a transgenic animal model of AD. Whole
      genome microarray gene expression profiling and biochemical analyses demonstrated
      that the centrally active ACE inhibitor captopril normalized the excessive
      hippocampal ACE activity of AD mice. Concomitantly, the development of signs of
      neurodegeneration was retarded by six months of captopril treatment. The
      neuroprotective profile triggered by captopril was accompanied by reduced
      amyloidogenic processing of the amyloid precursor protein (APP), and decreased
      hippocampal ROS, which is known to enhance Abeta generation by increased
      activation of beta- and gamma-secretases. Taken together, our data present strong
      evidence that ACE inhibition with a widely used cardiovascular drug could
      interfere with Abeta-dependent neurodegeneration. 

PMID- 23959129
TI  - Transporters: A yeast ABC interactome primer.

PMID- 23959130
TI  - Immunology: Cytosolic DNA sensing unraveled.

PMID- 23959131
TI  - Prevalence of unruptured intracranial aneurysms in healthy asymptomatic Japanese
      adults: differences in gender and age.
AB  - BACKGROUND: We aimed to assess the prevalence of unruptured intracranial
      aneurysms (UIAs) in healthy asymptomatic adults, and investigate the differences
      in incidence due to gender and age in Japan. METHODS: Magnetic resonance
      angiography (MRA) results of healthy asymptomatic adults who underwent the
      procedure for examination of the brain, from April 2010 to March 2012, were
      retrospectively examined. Patients with a history of ruptured aneurysm and UIAs
      were excluded. UIAs greater than 2.0 mm in size were counted. In accordance with
      these criteria, 8,696 people with a mean age of 52.2+/-9.5 years were examined,
      and 37.4 % of these individuals were women. RESULTS: The overall prevalence of
      UIAs was 3.2 %. The prevalence in women was higher than that in men (4.4 % versus
      2.5 %, OR, 1.81; 95% CI, 1.4 to 2.31). The prevalence increased with age in both
      genders. In under 49 years, the prevalence in women and men were 2.7 % and 1.9 %,
      respectively, with no significant differences (OR, 1.47; CI, 0.91 to 2.37). In
      over 50 years, the prevalence in women was higher than that in men (5.4 % versus
      2.8 %, OR, 2.01; CI, 1.52-2.67). There were significant differences in the
      locations of UIAs by gender (P <0.001); Internal carotid artery was more frequent
      in women, whereas anterior cerebral artery and middle cerebral artery were more
      common inmen. CONCLUSIONS: This study provides etiological data on the prevalence
      of UIAs in healthy asymptomatic Japanese adults, and may be useful in determining
      therapeutic managements for UIAs.

PMID- 23959134
TI  - 4th European Conference on Schizophrenia Research: Together for better treatment
      and care : 26-28 September 2013, Berlin, Germany.

PMID- 23959132
TI  - 4th European conference on schizophrenia research: together for better treatment
      and care.

PMID- 23959136
TI  - Organosilicon linkers in metal organic frameworks: the tetrahedral tetrakis(4
      tetrazolylphenyl)silane ligand.
AB  - Formal substitution of the central carbon by silicon within the tetrahedral
      tetrakis(4-tetrazolylphenyl)methane linker in a copper-based MOF is shown to
      uniquely influence the structure of the resultant MOF, affecting the orientation
      of the metal-based nodes and leading to an increase in unit-cell volume and
      solvent accessible void space. 

PMID- 23959135
TI  - Metagenomics uncovers a new group of low GC and ultra-small marine
      Actinobacteria.
AB  - We describe a deep-branching lineage of marine Actinobacteria with very low GC
      content (33%) and the smallest free living cells described yet (cell volume ca.
      0.013 MUm(3)), even smaller than the cosmopolitan marine photoheterotroph,
      'Candidatus Pelagibacter ubique'. These microbes are highly related to 16S rRNA
      sequences retrieved by PCR from the Pacific and Atlantic oceans 20 years ago.
      Metagenomic fosmids allowed a virtual genome reconstruction that also indicated
      very small genomes below 1 Mb. A new kind of rhodopsin was detected indicating a
      photoheterotrophic lifestyle. They are estimated to be ~4% of the total numbers
      of cells found at the site studied (the Mediterranean deep chlorophyll maximum)
      and similar numbers were estimated in all tropical and temperate photic zone
      metagenomes available. Their geographic distribution mirrors that of
      picocyanobacteria and there appears to be an association between these microbial
      groups. A new sub-class, 'Candidatus Actinomarinidae' is proposed to designate
      these microbes.

PMID- 23959138
TI  - Reply: To PMID 23429444.

PMID- 23959137
TI  - Differential modulation of brain nicotinic acetylcholine receptor function by
      cytisine, varenicline, and two novel bispidine compounds: emergent properties of
      a hybrid molecule.
AB  - Partial agonist therapies for the treatment of nicotine addiction and dependence
      depend on both agonistic and antagonistic effects of the ligands, and side
      effects associated with other nAChRs greatly limit the efficacy of nicotinic
      partial agonists. We evaluated the in vitro pharmacological properties of four
      partial agonists, two current smoking cessation drugs, varenicline and cytisine,
      and two novel bispidine compounds, BPC and BMSP, by using defined nAChR subtypes
      expressed in Xenopus laevis oocytes and human embryonic kidney 293 cells. Similar
      to varenicline and cytisine, BPC and BMSP are partial agonists of alpha4beta2
      nAChRs, although BMSP produced very little activation of these receptors. Unlike
      varenicline and cytisine, BPC and BMSP showed desired low activity. BPC produced
      mecamylamine-sensitive steady-state activation of alpha4* receptors that was not
      evident with BMSP. We evaluated the modulation of alpha4*- and alpha7-mediated
      responses in rat lateral geniculate nucleus (LGN) neurons and hippocampal stratum
      radiatum (SR) interneurons, respectively. The LGN neurons were sensitive to a
      very low concentration of varenicline, and the SR interneuron responses were also
      sensitive to varenicline at a submicromolar concentration. Although 300 nM BPC
      strongly inhibited the ACh-evoked responses of LGN neurons, it did not inhibit
      the alpha7 currents of SR interneurons. Similar results were observed with 300 nM
      BMSP. Additionally, the bispidine compounds were efficacious in the mouse tail
      suspension test, demonstrating that they affect receptors in the brain when
      delivered systemically. Our data indicate that BPC and BMSP are promising
      alpha4beta2* partial agonists for pharmacotherapeutics. 

PMID- 23959139
TI  - Electrostatics and flexibility drive membrane recognition and early penetration
      by the antimicrobial peptide dendrimer bH1.
AB  - Molecular dynamics simulations of the polycationic antimicrobial peptide
      dendrimer (Leu)8(DapLeu)4(DapPhe)2DapLys-NH2 binding to membranes suggest that
      electrostatic interactions with the polyanionic lipopolysaccharide (LPS) and
      conformational flexibility of the 2,3-diaminopropanoic acid (Dap) branching units
      drive its selective insertion into microbial membranes. 

PMID- 23959140
TI  - Targeting 5-HT(1A) receptors in astrocytes to protect dopaminergic neurons in
      Parkinsonian models.
AB  - Astrocytes are abundant neuron-supporting glial cells that harbor a powerful
      arsenal of neuroprotective antioxidative molecules and neurotrophic factors. Here
      we examined whether enrichment with healthy striatal astrocytes can provide
      neuroprotection against progressive dopaminergic neurodegeneration. Serotonin 1A
      (5-HT1A) agonist 8-OH-DPAT induced astrocyte proliferation and increased
      metallothionein-1/-2 (MT-1/-2), antioxidative molecules, in cultured astrocytes
      and the striatum of mice. Primary cultured mesencephalic dopamine neurons were
      protected against oxidative stress by preincubation with conditioned media from 8
      OH-DPAT-treated astrocytes. These protective effects were canceled by 5-HT1A
      antagonist or MT-1/-2-specific antibody. Furthermore, reduction of nigrostriatal
      dopaminergic neurons in 6-hydroxydopamine-lesioned parkinsonian model mice was
      significantly abrogated by repeated injections of 8-OH-DPAT. Treatment with 8-OH
      DPAT markedly increased the expression of MT in striatal astrocytes in the hemi
      parkinsonian mice. Our study provides a promising therapeutic strategy of
      neuroprotection against oxidative stress and progressive dopaminergic
      neurodegeneration by demonstrating the efficacy of targeting 5-HT1A receptors in
      astrocytes. 

PMID- 23959141
TI  - Epigenetic developmental programs and adipogenesis: implications for psychotropic
      induced obesity.
AB  - Psychotropic agents are notorious for their ability to increase fat mass in
      psychiatric patients. The two determinants of fat mass are the production of
      newly differentiated adipocytes (adipogenesis), and the volume of lipid
      accumulation. Epigenetic programs have a prominent role in cell fate commitments
      and differentiation required for adipogenesis. In parallel, epigenetic effects on
      energy metabolism are well supported by several genetic models. Consequently, a
      variety of psychotropics, often prescribed in combinations and for long periods,
      may utilize a common epigenetic effector path causing an increase in adipogenesis
      or reduction in energy metabolism. In particular, the recent discovery that G
      protein coupled signaling cascades can directly modify epigenetic regulatory
      enzymes implicates surface receptor activity by psychotropic medications. The
      potential therapeutic implications are also suggested by the effects of the
      clinically approved antidepressant tranylcypromine, also a histone demethylase
      inhibitor, which has impressive therapeutic effects on metabolism in the obese
      phenotype. 

PMID- 23959142
TI  - Biomarkers and brain connectivity.

PMID- 23959143
TI  - Impact of integrating HIV and TB care and treatment in a regional tuberculosis
      hospital in rural Guatemala.
AB  - Resource-limited settings have made slow progress in integrating TB and HIV care
      for co-infected patients. We examined the impact of integrated TB/HIV care on
      clinical and survival outcomes in rural western Guatemala. Prospective data from
      254 newly diagnosed TB/HIV patients (99 enrolled in the pre-integrated program
      from August 2005 to July 2006, and 155 enrolled in the integrated program from
      February 2008 to January 2009) showed no significant baseline differences between
      clients in the two periods. They were principally male (65.5 %), Mayan (71 %),
      median age 33 years, and CD4 count averaged 111 cells/mm3. TB/HIV co-infected
      patients were more likely to receive antiretroviral therapy in the integrated
      program than in the pre-integrated program (72 vs. 22 %, respectively) and had
      lower mortality (HR 0.22, 95 % CI 0.14-0.33). This study shows how using a TB
      setting as the entry point for integrated TB/HIV care can improve health outcomes
      for HIV-positive patients in rural Guatemala.

PMID- 23959144
TI  - Nanolayered manganese oxide/poly(4-vinylpyridine) as a biomimetic and very
      efficient water oxidizing catalyst: toward an artificial enzyme in artificial
      photosynthesis.
AB  - Nanolayered Mn oxide/poly(4-vinylpyridine) as a model for Mn cluster in
      photosystem II was synthesized and characterized using scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), dynamic light
      scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and UV-Visible
      spectroscopy (UV-Vis). The compound is a very efficient water oxidizing catalyst,
      and sizable oxygen evolution was detected at 50 mV overpotential at near neutral
      pH. The number is as low as the overpotential is used by nature in photosystem II
      of cyanobacteria, algae and green plants for similar reactions. 

PMID- 23959146
TI  - Cross-species analysis of thyroperoxidase inhibition by xenobiotics demonstrates
      conservation of response between pig and rat.
AB  - Thyroperoxidase (TPO), the enzyme that catalyzes the synthesis of thyroid
      hormone, is a known target for thyroid-disrupting chemicals. In vivo
      toxicological evidence supporting TPO-inhibition as one molecular-initiating
      event that leads to thyroid disruption is derived largely from rat models;
      however, a significant fraction of research on the inhibition of TPO by
      xenobiotics has been conducted using porcine TPO. The current work tested the
      hypothesis that porcine and rat thyroid microsomes exposed to TPO-inhibiting
      chemicals would demonstrate different responses in a guaiacol oxidation assay. A
      primary objective of this work is to establish the degree of concordance between
      rat and porcine TPO inhibition data. Microsomes were isolated from both rat and
      pig thyroid glands, and the guaiacol oxidation assay was performed for a training
      set of 12 chemicals, including previously reported TPO inhibitors, thyroid
      disrupting chemicals thought to perturb other targets, and several previously
      untested chemicals, to determine the relative TPO inhibition responses across
      species. Concentration-response curves were derived for methimazole (MMI),
      dibutylphthalate (DBP), diethylhexylphthalate (DEHP), diethylphthalate (DEP), 3,5
      dimethylpyrazole-1-methanol (DPM), iopanoic acid (IOA), 2-mercaptobenzothiazole
      (MBT), sodium perchlorate (PERC), p-nonylphenol (PNP), 4-propoxyphenol (4POP), 6
      propylthiouracil (PTU), and triclosan (TCS). MMI, PTU, MBT, DPM, 4POP, and at
      extremely high concentrations, PERC, inhibited TPO activity. Results demonstrated
      a strong qualitative concordance of response between the two species. All
      chemicals that inhibited TPO in porcine microsomes also inhibited TPO in rat
      microsomes. Hill model-derived IC50 values revealed approximate 1.5- to 50-fold
      differences in relative potency to MMI between species for positive chemicals.
      DPM, MBT, 4POP, and PTU exhibited greater relative potency to MMI using rat TPO
      versus porcine TPO, but rank order potency for inhibition was similar for the
      other test chemicals, with: PTU>MBT>DPM>4POP>PERC for rat TPO and
      MBT>PTU>DPM>4POP>PERC for porcine TPO. These data support the extrapolation of
      porcine TPO data to potential thyroid-disrupting activity in rodent models to
      evaluate TPO-inhibiting chemicals. 

PMID- 23959147
TI  - Two medical therapies very effective shortly after high levels of soman poisoning
      in rats, but only one with universal utility.
AB  - A treatment regimen consisting of HI-6, scopolamine, and physostigmine (termed
      the physostigmine regimen) has been based on the serendipitous discovery that it
      exerts powerful antidotal effects against high levels of soman poisoning if it is
      administered 1 min after exposure. A medical therapy with corresponding efficacy,
      but without the time limitation of the latter regimen, has been developed through
      studies of microinfusions of anticonvulsants into seizure controlling sites in
      the forebrain of rats. From these studies procyclidine emerged as the most potent
      anticonvulsant, and its potency was further enhanced when being combined with the
      antiepileptic levetiracetam during systemic administration. In the present study,
      the capacity of HI-6, levetiracetam, and procyclidine (termed the procyclidine
      regimen) was tested against that of the physostigmine regimen. The results showed
      that both regimens were very effective against supralethal doses of soman (3, 4,
      5 * LD50) when given 1 and 5 min after intoxication. When the treatments were
      administered 10 and 14 or 20 and 24 min after soman exposure, only the
      procyclidine regimen was able to terminate seizures and preserve lives. When used
      as prophylactic therapies, both regimens protected equally well against seizures,
      but only the procyclidine regimen provided neuroprotection. The procyclidine
      regimen has apparently capacities to serve as a universal therapy against soman
      intoxication in rats.

PMID- 23959148
TI  - Adsorption and separation of immunoglobulins by novel affinity core-shell beads
      decorated with Protein L and l-histidine.
AB  - A novel core shell beaded chromatographic materials was prepared by grafting of
      glycidyl methacrylate (GMA) on to the surface of poly(hydoxypropyl
      methacrylate/ethyleneglycol dimethacrylate), p(HPMA/EGDMA) beads via surface
      initiated atom transfer radical polymerization (SI-ATRP). For grafting GMA,
      p(HPMA/EGDMA) beads were first modified with an ATRP initiator. A reaction with 2
      bromo-2-methylpropionyl bromide of the hydroxyl groups of the beads led to ATRP
      initiator-covered surfaces. The grafted p(GMA) fibrous chains on the beads were
      decorated with two different ligands (i.e., Protein L and l-histidine) for
      separation of Immunoglobulin's (Igs) from aqueous solution in batch system. The
      maximum Igs adsorptions on the p(HPMA/EGDMA)-g-p(GMA)-Protein L and p(HPMA/EGDMA)
      g-p(GMA)-l-histidine affinity beads were found to be 81.8 and 112.3mg/g at pH 7.5
      and 5.5, respectively. The purity of Igs from human serum was analyzed by HPLC.
      The Protein L immobilized affinity beads provided purity about 98%. The novel
      core shell polymeric beads decorated with Protein L showed a good selectivity for
      Igs molecules from diluted human serum. Adsorption studies of Igs onto Protein L
      and l-histidine immobilized affinity beads were also carried out in a continuous
      system. 

PMID- 23959149
TI  - Tetragonal phase of epitaxial room-temperature antiferromagnet CuMnAs.
AB  - Recent studies have demonstrated the potential of antiferromagnets as the active
      component in spintronic devices. This is in contrast to their current passive
      role as pinning layers in hard disk read heads and magnetic memories. Here we
      report the epitaxial growth of a new high-temperature antiferromagnetic material,
      tetragonal CuMnAs, which exhibits excellent crystal quality, chemical order and
      compatibility with existing semiconductor technologies. We demonstrate its growth
      on the III-V semiconductors GaAs and GaP, and show that the structure is also
      lattice matched to Si. Neutron diffraction shows collinear antiferromagnetic
      order with a high Neel temperature. Combined with our demonstration of room
      temperature-exchange coupling in a CuMnAs/Fe bilayer, we conclude that tetragonal
      CuMnAs films are suitable candidate materials for antiferromagnetic spintronics. 

PMID- 23959150
TI  - Chain length and temperature dependence of alkanedithiol molecular conductance
      under ultra high vacuum.
AB  - We report scanning tunnelling microscope (STM) measurements of the single
      molecule conductance of alpha,omega-alkanedithiols for a large range of molecular
      chain lengths (N = 3-10) and temperatures (180-390 K) under ultra high vacuum.
      Two STM-based measurement techniques were employed on molecules trapped between
      tip and substrate: (i) the well established current-distance or I(z) technique
      and (ii) a new I(V,z) technique in which the current-voltage characteristics are
      determined as the tip-substrate distance z is varied. Low, medium, and high
      conductance groups were observed for each molecular length, which were
      temperature independent over the range examined, consistent with off-resonance
      tunnelling. For N > 4 the current-voltage characteristics and conductance trend
      with chain length is well described using a simple rectangular tunnel barrier
      model with parameters in excellent agreement with previously reported values.
      However, both 1,3-propanedithiol (N = 3) and 1,4-butanedithiol (N = 4) show an
      anomalous behaviour which is qualitatively similar to, but much less pronounced
      than, that reported by Haiss et al. (Phys. Chem. Chem. Phys., 2009, 11, 10831)
      for measurements performed under air and nitrogen gas. 

PMID- 23959151
TI  - Climate variability and oceanographic settings associated with interannual
      variability in the initiation of Dinophysis acuminata blooms.
AB  - In 2012, there were exceptional blooms of D. acuminata in early spring in what
      appeared to be a mesoscale event affecting Western Iberia and the Bay of Biscay.
      The objective of this work was to identify common climatic patterns to explain
      the observed anomalies in two important aquaculture sites, the Galician Rias
      Baixas (NW Spain) and Arcachon Bay (SW France). Here, we examine climate
      variability through physical-biological couplings, Sea Surface Temperature (SST)
      anomalies and time of initiation of the upwelling season and its intensity over
      several decades. In 2012, the mesoscale features common to the two sites were
      positive anomalies in SST and unusual wind patterns. These led to an atypical
      predominance of upwelling in winter in the Galician Rias, and increased haline
      stratification associated with a southward advection of the Gironde plume in
      Arcachon Bay. Both scenarios promoted an early phytoplankton growth season and
      increased stability that enhanced D. acuminata growth. Therefore, a common
      climate anomaly caused exceptional blooms of D. acuminata in two distant regions
      through different triggering mechanisms. These results increase our capability to
      predict intense diarrhetic shellfish poisoning outbreaks in the early spring from
      observations in the preceding winter. 

PMID- 23959153
TI  - Visual field constriction in a 42 year old woman.

PMID- 23959155
TI  - Half of Americans who buy their own health insurance will get tax credits, study
      finds.

PMID- 23959152
TI  - Clinical effectiveness of collaborative care for depression in UK primary care
      (CADET): cluster randomised controlled trial.
AB  - OBJECTIVE: To compare the clinical effectiveness of collaborative care with usual
      care in the management of patients with moderate to severe depression. DESIGN:
      Cluster randomised controlled trial. SETTING: 51 primary care practices in three
      primary care districts in the United Kingdom. PARTICIPANTS: 581 adults aged 18
      years and older who met ICD-10 (international classification of diseases, 10th
      revision) criteria for a depressive episode on the revised Clinical Interview
      Schedule. We excluded acutely suicidal patients and those with psychosis, or with
      type I or type II bipolar disorder; patients whose low mood was associated with
      bereavement or whose primary presenting problem was alcohol or drug abuse; and
      patients receiving psychological treatment for their depression by specialist
      mental health services. We identified potentially eligible participants by
      searching computerised case records in general practices for patients with
      depression. INTERVENTIONS: Collaborative care, including depression education,
      drug management, behavioural activation, relapse prevention, and primary care
      liaison, was delivered by care managers. Collaborative care involved six to 12
      contacts with participants over 14 weeks, supervised by mental health
      specialists. Usual care was family doctors' standard clinical practice. MAIN
      OUTCOME MEASURES: Depression symptoms (patient health questionnaire 9; PHQ-9),
      anxiety (generalised anxiety disorder 7; GAD-7), and quality of life (short form
      36 questionnaire; SF-36) at four and 12 months; satisfaction with service quality
      (client satisfaction questionnaire; CSQ-8) at four months. RESULTS: 276
      participants were allocated to collaborative care and 305 allocated to usual
      care. At four months, mean depression score was 11.1 (standard deviation 7.3) for
      the collaborative care group and 12.7 (6.8) for the usual care group. After
      adjustment for baseline depression, mean depression score was 1.33 PHQ-9 points
      lower (95% confidence interval 0.35 to 2.31, P=0.009) in participants receiving
      collaborative care than in those receiving usual care at four months, and 1.36
      points lower (0.07 to 2.64, P=0.04) at 12 months. Quality of mental health but
      not physical health was significantly better for collaborative care than for
      usual care at four months, but not 12 months. Anxiety did not differ between
      groups. Participants receiving collaborative care were significantly more
      satisfied with treatment than those receiving usual care. The number needed to
      treat for one patient to drop below the accepted diagnostic threshold for
      depression on the PHQ-9 was 8.4 immediately after treatment, and 6.5 at 12
      months. CONCLUSIONS: Collaborative care has persistent positive effects up to 12
      months after initiation of the intervention and is preferred by patients over
      usual care. TRIAL REGISTRATION NUMBER: ISRCTN32829227.

PMID- 23959156
TI  - Hospital waiting lists in England reach five year high.

PMID- 23959157
TI  - GPs warn of longer waiting times for appointments without more investment.

PMID- 23959158
TI  - ARMS2 interference leads to decrease of proinflammatory  mediators.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is a major cause of
      irreversible blindness among elderly people in developed countries. Many studies
      suggested that age-related maculopathy susceptibility 2 (ARMS2) is the second
      major susceptibility gene for AMD. Increasing evidence was found recently that
      inflammatory processes and oxidative stress may contribute to the pathogenesis of
      AMD. Meanwhile, the mechanisms underlying the contributions of ARMS2 to the
      pathogenesis of AMD remain unclear. The purpose of the current study was to
      elucidate the relationship between the ARMS2 gene and proinflammatory mediators,
      for further assessment of the associated biologic effects. METHODS: siRNA was
      used to knock down ARMS2 mRNA, and Western blotting and reverse real-time PCR
      were used to detect the effect of siRNA on the expression of ARMS2 in ARPE-19
      cells. The expressions of C3, C5, IL-6, IL-8, and TNF-alpha after si-RNA
      knockdown were evaluated by SYBR Green I real-time PCR and ELISA. RESULTS:
      Transcription accumulative indexes (TAI = 2(-delta delta CT)) of ARMS2 by real
      time PCR revealed that the transfection rate in the positive control group was
      72.0 +/- 2.07 % (P < 0.01). The ratio of absorbance values (by Western blotting)
      of AMRS2 to beta-actin was 0.85 +/- 0.122, 0.87 +/- 0.143, and 0.61 +/- 0.240 in
      the blank control group, scrambled ARMS2-siRNA group, and ARMS2-siRNA group
      respectively (F = 42.5, P < 0.01). The secreted protein levels of C3, C5, IL-6,
      IL-8, and TNF-alpha were found by ELISA to be reduced by 34.24 +/- 1.81 %, 37.15
      +/- 2.02 %, 35.11 +/- 1.75 %, 30.11 +/- 2.19 %, and 34.33 +/- 2.18 %
      respectively, in the siRNA-ARMS2 group (P < 0.05). Compared with the blank
      control group, reduced TAI of C3, C5, IL-6, IL-8, and TNF-alpha were detected by
      real-time PCR in the ARMS2-siRNA group. CONCLUSION: This study produced evidence
      supporting the notion that the ARMS2 risk allele for AMD is linked directly or
      indirectly to proinflammatory mediators. More importantly, our data indicate that
      the change in ARMS2 may affect C3, C5, IL-6, IL-8, and TNF-alpha levels, and this
      may be one of the mechanisms of AMD development.

PMID- 23959160
TI  - Change of laminin density stimulates axon branching via growth cone myosin II
      mediated adhesion.
AB  - Axon branching enables neurons to contact with multiple targets and respond to
      their microenvironment. Owing to its importance in neuronal network formation,
      axon branching has been studied extensively during the past decades. The chemical
      properties of extracellular matrices have been proposed to regulate axonal
      development, but the effects of their density changes on axon branching are not
      well understood. Here, we demonstrate that both the sharp broadening of substrate
      geometry and the sharp change of laminin density stimulate axon branching by
      using microcontact printing (MUCP) and microfluidic printing (MUFP) techniques.
      We also found that the change of axon branching stimulated by laminin density
      depends on myosin II activity. The change of laminin density induces asymmetric
      extensions of filopodia on the growth cone, which is the precondition for axon
      branching. These previously unknown mechanisms of change of laminin density
      stimulated axon branching may explain how the extracellular matrices regulate
      axon branching in vivo and facilitate the establishment of neuronal networks in
      vitro. 

PMID- 23959159
TI  - Antiphospholipid antibodies and sub-clinical atherosclerosis  in the Coronary
      Artery Risk Development in Young Adults  (CARDIA) cohort.
AB  - OBJECTIVE AND DESIGN: Antiphospholipid antibodies (APA) have been associated with
      clinical cardiovascular disease, but it remains unclear whether APA are
      associated with sub-clinical atherosclerosis. This study examined the
      relationship between APA and sub-clinical atherosclerosis, measured as coronary
      artery calcification (CAC), in participants from the prospective Coronary Artery
      Risk Development in Young Adults (CARDIA) Study. SUBJECTS AND METHOD: 2,203 black
      and white participants with sera available from the CARDIA year 7 examination and
      CAC measured by computed tomography at years 15 or 20 were selected. RESULTS:
      Anti-beta2-glycoprotein I (anti-beta2-GPI) immunoglobulin (Ig) M, IgG, and IgA
      were positive in 7.0, 1.4, and 1.8 % of participants, respectively; anti
      cardiolipin (aCL) IgM and IgG were positive in 1.5 and 1.0 %, respectively. 9.5 %
      of participants had CAC score >0 at year 15. Anti-beta2-GPI IgM, IgG, IgA, and
      aCL IgG positivity were associated with CAC >0 at year 15 after adjustment for
      traditional cardiovascular risk factors; [odds ratios (95 % confidence intervals)
      were 1.7 (1.0, 3.1), 6.4 (2.4, 16.8), 5.6 (2.3, 13.2), and 5.1 (1.4, 18.6),
      respectively]. Anti-beta2-GPI IgG was associated with year 20 CAC >0, and anti
      beta2-GPI IgA and aCL IgG were marginally associated. CONCLUSIONS: These findings
      indicate that APA positivity during young adulthood is a risk factor for
      subsequent sub-clinical atherosclerosis and might play a role in the pathogenesis
      of atherosclerosis

PMID- 23959161
TI  - Levodopa inhibits habit-learning in Parkinson's disease.
AB  - Mixed dopaminergic medication, comprising dopamine agonists and levodopa, may
      affect habit-learning in patients with Parkinson's disease (PD). However, the
      specific impact of levodopa on this effect is unknown. We assessed habit-learning
      in 20 non-demented PD-patients both with and without levodopa. We observed intact
      habit-learning in PD-patients OFF-medication. In contrast, the administration of
      200 mg of levodopa impaired habit-learning. We conclude that potential deficits
      in habit-learning in PD may be attributed to the intake of levodopa.

PMID- 23959162
TI  - Cholinergic manipulation of motor disability and L-DOPA-induced dyskinesia in 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets.
AB  - Anti-cholinergic drugs are used in the treatment of Parkinson's disease (PD) and
      they can improve motor disability in some patients and may alter the expression
      of dyskinesia. We report the effects of anticholinergic and pro-cholinergic
      agents administered alone and combined with L-DOPA, on motor function in 1-methyl
      4-phenyl-l,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets.
      Administration of atropine to MPTP-treated marmosets, not previously exposed to L
      DOPA, improved motor disability but this did not occur with other centrally
      acting anti-cholinergics. Motor disability was worsened by centrally acting pro
      cholinergics. However, neither peripherally acting anti- nor pro-cholinergics
      produced any effect on motor disability or dyskinesia. In MPTP-treated marmosets
      previously primed with L-DOPA to exhibit dyskinesia, acute L-DOPA challenge
      induced both chorea and dystonia. In these animals, centrally acting anti
      cholinergics including atropine and trihexyphenidyl reversed motor deficits, but
      induced chorea. Combined with L-DOPA, both centrally and peripherally acting anti
      cholinergics reduced peak locomotor activity and produced more chorea than
      dystonia compared to L-DOPA alone. Centrally acting pro-cholinergics decreased
      locomotor activity, worsened motor disability and induced dystonia. Co
      administered with L-DOPA, pro-cholinergics reduced locomotor activity and
      decreased chorea while increasing dystonia compared with L-DOPA alone. In
      conclusion, anti-cholinergics can increase chorea with and without L-DOPA but
      improve motor disability. Pro-cholinergics decrease the proportion of chorea when
      combined with L-DOPA, increase motor disability and antagonise L-DOPA's
      effectiveness. These data suggest that there may be a case for revisiting the use
      of anti-cholinergic drugs in the treatment of PD.

PMID- 23959164
TI  - Isolation and diversity of planctomycetes from the sponge Niphates sp., seawater,
      and sediment of Moreton Bay, Australia.
AB  - Planctomycetes are ubiquitous in marine environment and were reported to occur in
      association with multicellular eukaryotic organisms such as marine macroalgae and
      invertebrates. Here, we investigate planctomycetes associated with the marine
      sponge Niphates sp. from the sub-tropical Australian coast by assessing their
      diversity using culture-dependent and -independent approaches based on the 16S
      rRNA gene. The culture-dependent approach resulted in the isolation of a large
      collection of diverse planctomycetes including some novel lineages of
      Planctomycetes from the sponge as well as sediment and seawater of Moreton Bay
      where this sponge occurs. The characterization of these novel planctomycetes
      revealed that cells of one unique strain do not possess condensed nucleoids, a
      phenotype distinct from other planctomycetes. In addition, a culture-independent
      clone library approach identified unique planctomycete 16S rRNA gene sequences
      closely related to other sponge-derived sequences. The analysis of tissue of the
      sponge Niphates sp. showed that the mesohyl of the sponge is almost devoid of
      microbial cells, indicating this species is in the group of 'low microbial
      abundant' (LMA) sponges. The unique planctomycete 16S rRNA gene sequences
      identified in this study were phylogenetically closely related to sequences from
      LMA sponges in other published studies. This study has revealed new insights into
      the diversity of planctomycetes in the marine environment and the association of
      planctomycetes with marine sponges.

PMID- 23959163
TI  - Nonlinear growth kinetics of breast cancer stem cells: implications for cancer
      stem cell targeted therapy.
AB  - Cancer stem cells (CSCs) have been identified in primary breast cancer tissues
      and cell lines. The CSC population varies widely among cancerous tissues and cell
      lines, and is often associated with aggressive breast cancers. Despite of
      intensive research, how the CSC population is regulated within a tumor is still
      not well understood so far. In this paper, we present a mathematical model to
      explore the growth kinetics of CSC population both in vitro and in vivo. Our
      mathematical models and supporting experiments suggest that there exist non
      linear growth kinetics of CSCs and negative feedback mechanisms to control the
      balance between the population of CSCs and that of non-stem cancer cells. The
      model predictions can help us explain a few long-standing questions in the field
      of cancer stem cell research, and can be potentially used to predict the
      efficicacy of anti-cancer therapy. 

PMID- 23959165
TI  - Physiology and gene expression profiles of Dekkera  bruxellensis in response to
      carbon and nitrogen availability.
AB  - The assimilation of nitrate, a nitrogenous compound, was previously described as
      an important factor favoring Dekkera bruxellensis in the competition with
      Saccharomyces cerevisiae for the industrial sugarcane substrate. In this
      substrate, nitrogen sources are limited and diverse, and a recent report showed
      that amino acids enable D. bruxellensis to grow anaerobically. Thus,
      understanding the regulation of nitrogen metabolism is one fundamental aspect to
      comprehend the competiveness of D. bruxellensis in the fermentation environment.
      In the present study, we evaluated the physiological and transcriptional profiles
      of D. bruxellensis in response to different carbon and nitrogen supplies to
      determine their influence on growth, sugar consumption, and ethanol production.
      Besides, the expression of genes coding for nitrogen permeases and enzymes
      involved in the biosynthesis of glutamate and energetic metabolism were
      investigated under these conditions. Our data revealed that genes related to
      nitrogen uptake in D. bruxellensis are under the control of nitrogen catabolite
      repression. Moreover, we provide indications that glutamate dehydrogenase and
      glutamate synthase may switch roles as the major pathway for glutamate
      biosynthesis in D. bruxellensis. Finally, our data showed that in nonoptimal
      growth conditions, D. bruxellensis leans toward the respiratory metabolism. The
      results presented herein show that D. bruxellensis and S. cerevisiae share
      similar regulation of GDH-GOGAT pathway, while D. bruxellensis converts less
      glucose to ethanol than S. cerevisiae do when nitrogen is limited. The
      consequence of this particularity to the industrial process is discussed.

PMID- 23959167
TI  - Plasmid- and chromosomal genes-encoded two separate O-polysaccharide chains of
      Salmonella Uccle (O:3,54)--structural elucidation.
AB  - The bacterium Salmonella Uccle belongs to serotype O:54 in the Kauffmann'a-White
      scheme. Group O:54 is unique among the serogroups belonging to the genus
      Salmonella. Normally, the enzymes involved in the biosynthesis of the repeating
      units of somatic antigen are encoded by a set of genes, located in the region of
      the bacterial chromosome. Expression of O54 factor is associated with the
      presence of the plasmid. Factor O54 can be lost spontaneously in the subcultures
      of some serotypes. In these cases, the O54 negative variants become
      indistinguishable from the serotypes classified in other groups. We noticed lower
      activity of LPS-u O:3,54 with rabbit sera against antigens O:3, when compared
      with the activity of sera anti-A:54, which may indicate a partial inhibition of
      the expression of factor O:3 on the surface of the bacterial cell. The main aim
      of our study was to answer the question whether the products of different
      biosynthetic pathways combine on the outer side of the cytoplasmic membrane, thus
      forming a single chain or separate chains. Therefore, the O-polysaccharides (O
      antigen) of Salmonella Uccle O:3,54 were isolated by mild acid degradation of
      both obtained LPSs and their structure was established using sugar and
      methylation analysis and NMR spectroscopy. The primary structure of two separate
      O-polysaccharide chains isolated from Salmonella Uccle were established. 

PMID- 23959166
TI  - A bioengineered heterotypic stroma-cancer microenvironment model to study
      pancreatic ductal adenocarcinoma.
AB  - Interactions between neoplastic epithelial cells and components of a reactive
      stroma in pancreatic ductal adenocarcinoma (PDAC) are of key significance behind
      the disease's dismal prognosis. Despite extensive published research in the
      importance of stroma-cancer interactions in other cancers and experimental
      evidence supporting the importance of the microenvironment in PDAC progression, a
      reproducible three-dimensional (3D) in vitro model for exploring stroma-cancer
      interplay and evaluating therapeutics in a physiologically relevant context has
      been lacking. We introduce a humanized microfluidic model of the PDAC
      microenvironment incorporating multicellularity, extracellular matrix (ECM)
      components, and a spatially defined 3D microarchitecture. Pancreatic stellate
      cells (PSCs) isolated from clinically-evaluated human tissue specimens were co
      cultured with pancreatic ductal adenocarcinoma cells as an accessible 3D
      construct that maintained important tissue features and disease behavior.
      Multiphoton excitation (MPE) and Second Harmonic Generation (SHG) imaging
      techniques were utilized to image the intrinsic signal of stromal collagen in
      human pancreatic tissues and live cell-collagen interactions within the optically
      accessible microfluidic tissue model. We further evaluated the dose-response of
      the model with the anticancer agent paclitaxel. This bioengineered model of the
      PDAC stroma-cancer microenvironment provides a complementary platform to
      elucidate the complex stroma-cancer interrelationship and to evaluate the
      efficacy of potential therapeutics in a humanized system that closely
      recapitulates key PDAC microenvironment characteristics. 

PMID- 23959168
TI  - The biogenesis protein PEX14 is an optimal marker for the identification and
      localization of peroxisomes in different cell types, tissues, and species in
      morphological studies.
AB  - Catalase and ABCD3 are frequently used as markers for the localization of
      peroxisomes in morphological experiments. Their abundance, however, is highly
      dependent on metabolic demands, reducing the validity of analyses of peroxisomal
      abundance and distribution based solely on these proteins. We therefore attempted
      to find a protein which can be used as an optimal marker for peroxisomes in a
      variety of species, tissues, cell types and also experimental designs,
      independently of peroxisomal metabolism. We found that the biogenesis protein
      peroxin 14 (PEX14) is present in comparable amounts in the membranes of every
      peroxisome and is optimally suited for immunoblotting, immunohistochemistry,
      immunofluorescence, and immunoelectron microscopy. Using antibodies against
      PEX14, we could visualize peroxisomes with almost undetectable catalase content
      in various mammalian tissue sections (submandibular and adrenal gland, kidney,
      testis, ovary, brain, and pancreas from mouse, cat, baboon, and human) and cell
      cultures (primary cells and cell lines). Peroxisome labeling with catalase often
      showed a similar tissue distribution to the mitochondrial enzyme mitochondrial
      superoxide dismutase (both responsible for the degradation of reactive oxygen
      species), whereas ABCD3 exhibited a distinct labeling only in cells involved in
      lipid metabolism. We increased the sensitivity of our methods by using
      QuantumDotsTM, which have higher emission yields compared to classic
      fluorochromes and are unsusceptible to photobleaching, thereby allowing more
      exact quantification without artificial mistakes due to heterogeneity of
      individual peroxisomes. We conclude that PEX14 is indeed the best marker for
      labeling of peroxisomes in a variety of tissues and cell types in a consistent
      fashion for comparative morphometry.

PMID- 23959169
TI  - Adhesion, proliferation, and differentiation of mesenchymal stem cells on RGD
      nanopatterns of varied nanospacings.
AB  - The present report is an extension of our preceding publication in Biomaterials
      (2013) entitled "Effect of RGD nanospacing on differentiation of stem cells."
      Cell-adhesive peptide arginine-glycine-aspartate (RGD) was nanopatterned on a non
      fouling poly(ethylene glycol) (PEG) hydrogel, and mesenchymal stem cells (MSCs)
      derived from rat bone marrow were cultured on the patterned surfaces at
      nanospacings from 37 to 124 nm. Cell adhesion parameters such as spreading areas
      varied with RGD nanospacings significantly. The differences were well observed at
      both the first and eighth days, which confirmed the persistence of this
      nanospacing effect on our nanopatterns. The proliferation rate also varied with
      the nanospacings. Osteogenic and adipogenic inductions were undertaken, and a
      significant influence of RGD nanospacing on stem cell differentiation was found.
      The effect on differentiation cannot be simply interpreted by differences in cell
      adhesion and proliferation. We further calculated the fractions of single,
      coupled, and multiple cells on those nanopatterns, and ruled out the possibility
      that the extent of cell-cell contact determined the different differentiation
      fractions. Accordingly, we reinforced the idea that RGD nanospacing might
      directly influence stem cell differentiation. 

PMID- 23959170
TI  - Protective effect of bilberry (Vaccinium myrtillus L.) on cisplatin induced
      ovarian damage in rat.
AB  - Cisplatin is one of the most effective chemotherapeutic agents but injury may
      occur at higher doses. The aim of this study was to investigate the effect of
      bilberry on cisplatin induced toxic effects in rat ovary. Twenty-one female
      Wistar-Albino rats were utilized to form three groups: In group 1 (control
      group), each rat received intraperitoneal injection of 1 mL of 0.9 % NaCl saline
      solution during 10-days. In group 2 (cisplatin group), a single dose of 7.5 mg/kg
      b.w. cisplatin was given. In group 3 (cisplatin + bilberry group), a single dose
      of 7.5 mg/kg cisplatin and bilberry at 200 mg/kg b.w. were given for 10 days.
      Ovaries were surgically removed in all groups and prepared for biochemical and
      light microscopic investigations at the examination times. Malondialdehyde (MDA)
      levels and activities of superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GPx) and glutathione-S-transferase (GST) of tissue samples were
      measured. Histopathological damages in cisplatin administrated rats were seen
      such as severe edema, vascular congestion, hemorrhage and follicular degeneration
      in the ovary tissue. Moderate pathological alterations were observed in rats
      treated with bilberry plus cisplatin. Cisplatin administration significantly
      increased MDA production and decreased SOD, CAT, GPx and GST activities in the
      ovarian tissue when compared to the control group (p < 0.05). Cisplatin +
      bilberry administration increased antioxidant enzymes activities and reduced MDA
      levels. Bilberry administration seems to reduce the cisplatin induced ovarian
      toxicity thus it alleviates free radical damage. But it dose not protect
      completely rat ovary tissues. 

PMID- 23959171
TI  - Molecular mechanisms of CRISPR-mediated microbial immunity.
AB  - Bacteriophages (phages) infect bacteria in order to replicate and burst out of
      the host, killing the cell, when reproduction is completed. Thus, from a
      bacterial perspective, phages pose a persistent lethal threat to bacterial
      populations. Not surprisingly, bacteria evolved multiple defense barriers to
      interfere with nearly every step of phage life cycles. Phages respond to this
      selection pressure by counter-evolving their genomes to evade bacterial
      resistance. The antagonistic interaction between bacteria and rapidly
      diversifying viruses promotes the evolution and dissemination of bacteriophage
      resistance mechanisms in bacteria. Recently, an adaptive microbial immune system,
      named clustered regularly interspaced short palindromic repeats (CRISPR) and
      which provides acquired immunity against viruses and plasmids, has been
      identified. Unlike the restriction-modification anti-phage barrier that subjects
      to cleavage any foreign DNA lacking a protective methyl-tag in the target site,
      the CRISPR-Cas systems are invader-specific, adaptive, and heritable. In this
      review, we focus on the molecular mechanisms of interference/immunity provided by
      different CRISPR-Cas systems.

PMID- 23959172
TI  - Swiprosin-1 modulates actin dynamics by regulating the F-actin accessibility to
      cofilin.
AB  - Membrane protrusions, like lamellipodia, and cell movement are dependent on actin
      dynamics, which are regulated by a variety of actin-binding proteins acting
      cooperatively to reorganize actin filaments. Here, we provide evidence that
      Swiprosin-1, a newly identified actin-binding protein, modulates lamellipodial
      dynamics by regulating the accessibility of F-actin to cofilin. Overexpression of
      Swiprosin-1 increased lamellipodia formation in B16F10 melanoma cells, whereas
      knockdown of Swiprosin-1 inhibited EGF-induced lamellipodia formation, and led to
      a loss of actin stress fibers at the leading edges of cells but not in the cell
      cortex. Swiprosin-1 strongly facilitated the formation of entangled or clustered
      F-actin, which remodeled the structural organization of actin filaments making
      them in accessible to cofilin. EGF-induced phosphorylation of Swiprosin-1 at
      Ser183, a phosphorylation site newly identified using mass spectrometry,
      effectively inhibited clustering of actin filaments and permitted cofilin access
      to F-actin, resulting in actin depolymerization. Cells over expressing a
      Swiprosin-1 phosphorylation-mimicking mutant or a phosphorylation-deficient
      mutant exhibited irregular membrane dynamics during the protrusion and retraction
      cycles of lamellipodia. Taken together, these findings suggest that dynamic
      exchange of Swiprosin-1 phosphorylation and dephosphorylation is a novel
      mechanism that regulates actin dynamics by modulating the pattern of cofilin
      activity at the leading edges of cells.

PMID- 23959173
TI  - Cerebrospinal fluid Abeta42, phosphorylated Tau181, and resting-state functional
      connectivity.
AB  - IMPORTANCE: Resting-state functional connectivity magnetic resonance imaging has
      great potential for characterizing pathophysiological changes during the
      preclinical phase of Alzheimer disease. OBJECTIVE: To assess the relationship
      between default mode network integrity and cerebrospinal fluid biomarkers of
      Alzheimer disease pathology in cognitively normal older individuals. DESIGN,
      SETTING, AND PARTICIPANTS: Cross-sectional cohort study at The Charles F. and
      Joanne Knight Alzheimer's Disease Research Center at Washington University in St
      Louis, St Louis, Missouri, among 207 older adults with normal cognition (Clinical
      Dementia Rating, 0). MAIN OUTCOMES AND MEASURES: Resting-state functional
      connectivity magnetic resonance imaging measures of default mode network
      integrity. RESULTS: Decreased cerebrospinal fluid Abeta42 and increased
      cerebrospinal fluid phosphorylated tau181 were independently associated with
      reduced default mode network integrity, with the most prominent decreases in
      functional connectivity observed between the posterior cingulate and medial
      temporal regions. Observed reductions in functional connectivity were
      unattributable to age or structural atrophy in the posterior cingulate and medial
      temporal areas. Similar resting-state functional connectivity magnetic resonance
      imaging findings in relation to cerebrospinal fluid biomarkers were obtained
      using region-of-interest analyses and voxelwise correlation mapping. CONCLUSIONS
      AND RELEVANCE: Both Abeta and tau pathology affect default mode network integrity
      before clinical onset of Alzheimer disease.

PMID- 23959174
TI  - Ribophorin II regulates breast tumor initiation and metastasis through the
      functional suppression of GSK3beta.
AB  - Mutant p53 (mtp53) gain of function (GOF) contributes to various aspects of tumor
      progression including cancer stem cell (CSC) property acquisition. A key factor
      of GOF is stabilization and accumulation of mtp53. However, the precise molecular
      mechanism of the mtp53 oncogenic activity remains unclear. Here, we show that
      ribophorin II (RPN2) regulates CSC properties through the stabilization of mtp53
      (R280K and del126-133) in breast cancer. RPN2 stabilized mtp53 by inactivation of
      glycogen synthase kinase-3beta (GSK3beta) which suppresses Snail, a master
      regulator of epithelial to mesenchymal transition. RPN2 knockdown promoted
      GSK3beta-mediated suppression of heat shock proteins that are essential for mtp53
      stabilization. Furthermore, our study reveals that high expression of RPN2 and
      concomitant accumulation of mtp53 were associated with cancer tissues in a small
      cohort of metastatic breast cancer patients. These findings elucidate a molecular
      mechanism for mtp53 stabilization and suggest that RPN2 could be a promising
      target for anti-CSC therapy. 

PMID- 23959175
TI  - Into the wild: digging at immunology's evolutionary roots.
AB  - The two pillars of modern immunology have been man and mouse; in both settings,
      investigators seek to reduce complexity and control environmental conditions.
      However, the world outside the laboratory is immensely variable; this is not
      'noise' but represents the genetic and environmental framework in which the
      immune system evolved and functions. Placing the ever-growing understanding of
      immunological mechanisms in wider real-world contexts is a massive but
      fundamentally important challenge. 

PMID- 23959176
TI  - IFN-beta-specific signaling via a unique IFNAR1 interaction.

PMID- 23959177
TI  - Resolving the mystery of pyrophosphate antigen presentation.

PMID- 23959178
TI  - The danger of sex and death in Scarf1(-/-) autoimmune mice.

PMID- 23959179
TI  - DCs: a dual bridge to protective immunity.

PMID- 23959187
TI  - Medial supracondylar stress fracture in an adolescent pitcher/.
AB  - We report the occurrence of a medial supracondylar stress fracture in an
      adolescent pitcher. To our knowledge, this fracture has not been described in the
      literature, and awareness of this entity allows initiation of therapy and
      precludes further unnecessary work-up. The radiographic, computed tomography, and
      magnetic resonance imaging appearances are reviewed and the mechanism of injury
      is discussed.

PMID- 23959188
TI  - Unsorted single walled carbon nanotubes enabled the fabrication of high
      performance organic thin film transistors with low cost metal electrodes.
AB  - Transistors with a diketopyrrolopyrrole-quarterthiophene (DPP-QT) semiconductor
      and low-cost Al or Cu electrodes were studied. Albeit a large charge injection
      resistance exists between DPP-QT and Al or Cu, the resistance was dramatically
      reduced when unsorted single walled carbon nanotubes (SWCNTs) were blended into
      the DPP-QT film. This led to a high mobility of 0.64 and 1.1 cm(2) V(-1) s(-1),
      respectively, for Al and Cu devices, which is similar or even better than the
      device using gold electrodes (0.78 cm(2) V(-1) s(-1)). 

PMID- 23959186
TI  - Sterols and oxysterols in immune cell function.
AB  - Intermediates in the cholesterol-biosynthetic pathway and oxysterol derivatives
      of cholesterol regulate diverse cellular processes. Recent studies have expanded
      the appreciation of their roles in controlling the functions of cells of the
      innate and adaptive immune systems. Here we review recent literature reporting on
      the biological functions of sterol intermediates and oxysterols, acting through
      transcription factors such as the liver X receptors (LXRs), sterol regulatory
      element-binding proteins (SREBPs) and the G protein-coupled receptor EBI2, in
      regulating the differentiation and population expansion of cells of the innate
      and adaptive immune systems, their responses to inflammatory mediators, their
      effects on the phagocytic functions of macrophages and their effects on antiviral
      activities and the migration of immune cells. Such findings have raised many new
      questions about the production of endogenous bioactive sterols and oxysterols and
      their mechanisms of action in the immune system. 

PMID- 23959190
TI  - Heart rate variability biofeedback improves cardiorespiratory resting function
      during sleep.
AB  - The present study was designed to examine the effect of heart rate variability
      (HRV) biofeedback on the cardiorespiratory resting function during sleep in daily
      life. Forty-five healthy young adults were randomly assigned to one of three
      groups: HRV biofeedback, Autogenic Training(AT), and no-treatment control.
      Participants in the HRV biofeedback were instructed to use a handheld HRV
      biofeedback device before their habitual bedtime, those in the AT were asked to
      listen to an audiotaped instruction before bedtime,and those in the control were
      asked to engage in their habitual activity before bedtime. Pulse wave signal
      during sleep at their own residences was measured continuously with a wrist watch
      type transdermal photoelectric sensor for three time points. Baseline data were
      collected on the first night of measurements, followed by two successive nights
      for HRV biofeedback, AT, or control. Cardiorespiratory resting function was
      assessed quantitatively as the amplitude of high frequency(HF) component of pulse
      rate variability, a surrogate measure of respiratory sinus arrhythmia. HF
      component increased during sleep in the HRV biofeedback group,although it
      remained unchanged in the AT and control groups. These results suggest that HRV
      biofeedback before sleep may improve cardiorespiratory resting function during
      sleep.

PMID- 23959189
TI  - S-like ribonuclease gene expression in carnivorous plants.
AB  - Functions of S-like ribonucleases (RNases) differ considerably from those of S
      RNases that function in self-incompatibility. Expression of S-like RNases is
      usually induced by low nutrition, vermin damage or senescence. However,
      interestingly, an Australian carnivorous plant Drosera adelae (a sundew), which
      traps prey with a sticky digestive liquid, abundantly secretes an S-like RNase DA
      I in the digestive liquid even in ordinary states. Here, using D. adelae, Dionaea
      muscipula (Venus flytrap) and Cephalotus follicularis (Australian pitcher plant),
      we show that carnivorous plants use S-like RNases for carnivory: the gene da-I
      encoding DA-I and its ortholog cf-I of C. follicularis are highly expressed and
      constitutively active in each trap/digestion organ, while the ortholog dm-I of D.
      muscipula becomes highly active after trapping insects. The da-I promoter is
      unmethylated only in its trap/digestion organ, glandular tentacles (which
      comprise a small percentage of the weight of the whole plant), but methylated in
      other organs, which explains the glandular tentacles-specific expression of the
      gene and indicates a very rare gene regulation system. In contrast, the promoters
      of dm-I, which shows induced expression, and cf-I, which has constitutive
      expression, were not methylated in any organs examined. Thus, it seems that the
      regulatory mechanisms of the da-I, dm-I and cf-I genes differ from each other and
      do not correlate with the phylogenetic relationship. The current study suggests
      that under environmental pressure in specific habitats carnivorous plants have
      managed to evolve their S-like RNase genes to function in carnivory.

PMID- 23959191
TI  - Chemical composition and biological activities of essential oils of Eremanthus
      erythropappus (DC) McLeisch (Asteraceae).
AB  - The chemical composition of the essential oils obtained by hydrodistillation of
      different parts of Eremanthus erythropappus, including leaves, branches and
      inflorescences, was investigated by Gas Chromatography and Gas
      Chromatography/Mass Spectrometry. The antimicrobial activity of the oils was
      assessed by the disc diffusion and microdilution methods, while the antioxidant
      activity was evaluated by DPPH and reducing power tests. The main compounds found
      in the essential oils derived from the inflorescences and leaves were beta
      caryophyllene, germacrene-D, alpha-copaene and beta-pinene. alpha-Bisabolol was
      the major component in the branches. The oils were active against Staphylococcus
      aureus, Streptococcus pyogenes and fungi, but not Escherichia coli and
      Pseudomonas aeruginosa. The MIC values ranged from 0.01 to 0.50 mg/mL. Using the
      DPPH test, the IC50 values ranged from 38.77 +/- 0.76 to 102.24 +/- 1.96 MUg/mL,
      while the reducing power test produced IC50 values between 109.85 +/- 1.68 and
      169.53 +/- 0.64 MUg/mL. The results revealed that the E. erythropappus oils are
      new promising potential sources of antimicrobial and antioxidant compounds with
      good future practical applications for human health. 

PMID- 23959193
TI  - Eco-friendly synthesis and antiproliferative evaluation of some oxygen
      substituted diaryl ketones.
AB  - A broad variety of oxygen-substituted diaryl ketones has been synthesized by
      solar energy-induced Friedel Crafts acylations of 1,4-benzo- and 1,4
      naphthoquinones with benzaldehydes. The in vitro antiproliferative properties of
      the photoproducts were assessed on prostate (DU-145), bladder (T24) and breast
      (MCF7) human-derived tumor cell lines and compared to non-tumor mouse fibroblasts
      (Balb/3T3). Among the tested compounds, it was found that those containing a
      3,4,5-trimethoxyphenyl A-ring, such as 12 and 22 are more active on DU-145, with
      EC50 values of 1.2 and 5.9 MUM, respectively. By comparing their effects on the
      three cancer cell lines, the analogue 22 has the best mean selective index (2.4).

PMID- 23959192
TI  - Click chemistry in peptide-based drug design.
AB  - Click chemistry is an efficient and chemoselective synthetic method for coupling
      molecular fragments under mild reaction conditions. Since the advent in 2001 of
      methods to improve stereochemical conservation, the click chemistry approach has
      been broadly used to construct diverse chemotypes in both chemical and biological
      fields. In this review, we discuss the application of click chemistry in peptide
      based drug design. We highlight how triazoles formed by click reactions have been
      used for mimicking peptide and disulfide bonds, building secondary structural
      components of peptides, linking functional groups together, and bioconjugation.
      The progress made in this field opens the way for synthetic approaches to convert
      peptides with promising functional leads into structure-minimized and more stable
      forms. 

PMID- 23959194
TI  - ADIBO-based "click" chemistry for diagnostic peptide micro-array fabrication:
      physicochemical and assay characteristics.
AB  - Several azide-derivatized and fluorescently-labeled peptides were immobilized on
      azadibenzocyclooctyne (ADIBO)-activated slide surfaces via a strain-promoted
      alkyne-azide cycloaddition (SPAAC) reaction revealing excellent immobilization
      kinetics, good spot homogeneities and reproducible fluorescence signal
      intensities. A myc-peptide micro-array immunoassay showed an antibody limit-of
      detection (LOD) superior to a microtiter plate-based ELISA. Bovine serum albumin
      (BSA) and dextran covalently attached via "click" chemistry more efficiently
      reduced non-specific binding (NSB) of fluorescently-labeled IgG to the microarray
      surface in comparison to immobilized hexanoic acid and various types of
      polyethylene glycol (PEG) derivatives. Confirmation of these findings via further
      studies with other proteins and serum components could open up new possibilities
      for human sample and microarray platform-based molecular diagnostic tests. 

PMID- 23959195
TI  - Breathing some new life into an old topic: chalcogen-nitrogen pi-heterocycles as
      electron acceptors.
AB  - Recent progress in the design, synthesis and characterization of chalcogen
      nitrogen pi-heterocycles, mostly 1,2,5-chalcogenadiazoles (chalcogen: S, Se and
      Te) and their fused derivatives, possessing positive electron affinity is
      discussed together with their use in preparation of charge-transfer complexes and
      radical-anion salts-candidate building blocks of molecule-based electrical and
      magnetic functional materials. 

PMID- 23959196
TI  - Kinetics of nitric oxide and oxygen gases on porous Y-stabilized ZrO2-based
      sensors.
AB  - Using impedance spectroscopy the electrical response of sensors with various
      porous Y-stabilized ZrO2 (YSZ) microstructures was measured for gas
      concentrations containing 0-100 ppm NO with 10.5%O2 at temperatures ranging from
      600-700  degrees C. The impedance response increased substantially as the sensor
      porosity increased from 46%-50%. Activation energies calculated based on data
      from the impedance measurements increased in magnitude (97.4-104.9 kJ/mol for 100
      ppm NO) with respect to increasing YSZ porosity. Analysis of the oxygen partial
      pressure dependence of the sensors suggested that dissociative adsorption was the
      dominant rate limiting. The PWC/DNP theory level was used to investigate the gas
      phase energy barrier of the 2NO+O2 -> 2NO2 reaction on a 56-atom YSZ/Au model
      cluster using Density Functional Theory and Linear Synchronous Transit/Quadratic
      Synchronous Transit calculations. The reaction path shows oxygen surface
      reactions that begin with NO association with adsorbed O2 on a Zr surface site,
      followed by O2 dissociative adsorption, atomic oxygen diffusion, and further NO2
      formation. The free energy barrier was calculated to be 181.7 kJ/mol at PWC/DNP.
      A qualitative comparison with the extrapolated data at 62% +/- 2% porosity
      representing the YSZ model cluster indicates that the calculated barriers are in
      reasonable agreement with experiments, especially when the RPBE functional is
      used.

PMID- 23959197
TI  - Chemistry and Antiviral Activity of Arrabidaea pulchra (Bignoniaceae).
AB  - The aim of the present work was to carry out a bioguided isolation of antiviral
      chemical constituents from an ethanol extract of leaves from Arrabidaea pulchra
      (Cham.) Sandwith (EEAPL) that had shown in vitro activity in a previous screening
      using DNA and RNA viruses. The activity of EEPAL was evaluated against the DNA
      viruses Human herpesvirus 1 (HSV-1) and Vaccinia virus Western Reserve (VACV-WR)
      as well as against the RNA viruses Murine encephalomyocarditis virus (EMCV), and
      Dengue virus 2 (DENV-2) by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) colorimetric assay. Cytotoxicity was determined
      in LLCMK2 and Vero cells and the Selectivity Indexes (SI) were calculated. The
      most potent effect was observed against DENV-2 (EC50 46.8 +/- 1.6 ug mL(-1); SI
      2.7). For HSV-1 and VACV-WR EC50 values > 200 ug mL(-1) were determined, while no
      inhibition of the cytopathic effect was observed with EMCV. Bioguided
      fractionation of EEAPL by partition between immiscible solvents followed by
      chromatography over a Sephadex LH20 column afforded two arylpropanoid glycosides,
      verbascoside (AP 1) and caffeoylcalleryanin (AP 2), along with a terpenoid,
      ursolic acid (AP 3). AP 1 and AP 3 exhibited similar anti-DENV-2 profiles, with
      SI values of 3.8 and 3.1, respectively, while AP 2 was the most effective anti
      DENV-2 constituent, with a SI of 20.0. Our results show that A. pulchra leaves
      ethanol extract (EEAPL) affords compounds with antiviral activity, mainly against
      DENV-2.

PMID- 23959198
TI  - PET neuroimaging: the white elephant packs his trunk?

PMID- 23959199
TI  - Age-related changes in the structure and function of prefrontal cortex-amygdala
      circuitry in children and adolescents: a multi-modal imaging approach.
AB  - The uncinate fasciculus is a major white matter tract that provides a crucial
      link between areas of the human brain that underlie emotion processing and
      regulation. Specifically, the uncinate fasciculus is the major direct fiber tract
      that connects the prefrontal cortex and the amygdala. The aim of the present
      study was to use a multi-modal imaging approach in order to simultaneously
      examine the relation between structural connectivity of the uncinate fasciculus
      and functional activation of the amygdala in a youth sample (children and
      adolescents). Participants were 9 to 19years old and underwent diffusion tensor
      imaging (DTI) and functional magnetic resonance imaging (fMRI). Results indicate
      that greater structural connectivity of the uncinate fasciculus predicts reduced
      amygdala activation to sad and happy faces. This effect is moderated by age, with
      younger participants exhibiting a stronger relation. Further, decreased amygdala
      activation to sad faces predicts lower internalizing symptoms. These results
      provide important insights into brain structure-function relationships during
      adolescence, and suggest that greater structural connectivity of the uncinate
      fasciculus may facilitate regulation of the amygdala, particularly during early
      adolescence. These findings also have implications for understanding the relation
      between brain structure, function, and the development of emotion regulation
      difficulties, such as internalizing symptoms. 

PMID- 23959200
TI  - Neural correlates of experimentally induced flow experiences.
AB  - Flow refers to a positive, activity-associated, subjective experience under
      conditions of a perceived fit between skills and task demands. Using functional
      magnetic resonance perfusion imaging, we investigated the neural correlates of
      flow in a sample of 27 human subjects. Experimentally, in the flow condition
      participants worked on mental arithmetic tasks at challenging task difficulty
      which was automatically and continuously adjusted to individuals' skill level.
      Experimental settings of "boredom" and "overload" served as comparison
      conditions. The experience of flow was associated with relative increases in
      neural activity in the left anterior inferior frontal gyrus (IFG) and the left
      putamen. Relative decreases in neural activity were observed in the medial
      prefrontal cortex (MPFC) and the amygdala (AMY). Subjective ratings of the flow
      experience were significantly associated with changes in neural activity in the
      IFG, AMY, and, with trend towards significance, in the MPFC. We conclude that
      neural activity changes in these brain regions reflect psychological processes
      that map on the characteristic features of flow: coding of increased outcome
      probability (putamen), deeper sense of cognitive control (IFG), decreased self
      referential processing (MPFC), and decreased negative arousal (AMY). 

PMID- 23959201
TI  - A longitudinal study of brain atrophy over two years in community-dwelling older
      individuals.
AB  - Most previous neuroimaging studies of age-related brain structural changes in
      older individuals have been cross-sectional and/or restricted to clinical
      samples. The present study of 345 community-dwelling non-demented individuals
      aged 70-90years aimed to examine age-related brain volumetric changes over two
      years. T1-weighted magnetic resonance imaging scans were obtained at baseline and
      at 2-year follow-up and analyzed using the FMRIB Software Library and FreeSurfer
      to investigate cortical thickness and shape and volumetric changes of subcortical
      structures. The results showed significant atrophy across much of the cerebral
      cortex with bilateral transverse temporal regions shrinking the fastest. Atrophy
      was also found in a number of subcortical structures, including the CA1 and
      subiculum subfields of the hippocampus. In some regions, such as left and right
      entorhinal cortices, right hippocampus and right precentral area, the rate of
      atrophy increased with age. Our analysis also showed that rostral middle frontal
      regions were thicker bilaterally in older participants, which may indicate its
      ability to compensate for medial temporal lobe atrophy. Compared to men, women
      had thicker cortical regions but greater rates of cortical atrophy. Women also
      had smaller subcortical structures. A longer period of education was associated
      with greater thickness in a number of cortical regions. Our results suggest a
      pattern of brain atrophy with non-demented people that resembles a less extreme
      form of the changes associated with Alzheimer's disease (AD). 

PMID- 23959203
TI  - A portable explosive detector based on fluorescence quenching of pyrene deposited
      on coloured wax-printed MUPADs.
AB  - A new technique for the detection of explosives has been developed based on
      fluorescence quenching of pyrene on paper-based analytical devices (MUPADs). Wax
      barriers were generated (150  degrees C, 5 min) using ten different colours.
      Magenta was found as the most suitable wax colour for the generation of the
      hydrophobic barriers with a nominal width of 120 MUm resulting in fully
      functioning hydrophobic barriers. One microliter of 0.5 mg mL(-1) pyrene
      dissolved in an 80:20 methanol-water solution was deposited on the hydrophobic
      circle (5 mm diameter) to produce the active microchip device. Under ultra-violet
      (UV) illumination, ten different organic explosives were detected using the
      MUPAD, with limits of detection ranging from 100-600 ppm. A prototype of a
      portable battery operated instrument using a 3 W power UV light-emitting-diode
      (LED) (365 nm) and a photodiode sensor was also built and evaluated for the
      successful automatic detection of explosives and potential application for field
      based screening.

PMID- 23959202
TI  - Brain mitochondrial oxidative metabolism during and after cerebral hypoxia
      ischemia studied by simultaneous phosphorus magnetic-resonance and broadband near
      infrared spectroscopy.
AB  - BACKGROUND: Multimodal measurements combining broadband near-infrared
      spectroscopy (NIRS) and phosphorus magnetic resonance spectroscopy ((31)P MRS)
      assessed associations between changes in the oxidation state of cerebral
      mitochondrial cytochrome-c-oxidase (Delta[oxCCO]) and (31)P metabolite peak-area
      ratios during and after transient cerebral hypoxia-ischemia (HI) in the newborn
      piglet. METHODS: Twenty-four piglets (aged<24 h) underwent transient HI (inspired
      oxygen fraction 9% and bilateral carotid artery occlusion for ~20 min). Whole
      brain (31)P MRS and NIRS data were acquired every minute. Inorganic phosphate
      (Pi)/epp, phosphocreatine (PCr)/epp, and total nucleotide triphosphate (NTP)/epp
      were measured by (31)P MRS and were plotted against Delta[oxCCO] during HI and
      recovery (epp=exchangeable phosphate pool=Pi+PCr+2gamma-NTP+beta-NTP). RESULTS:
      During HI Delta[oxCCO], PCr/epp and NTP/epp declined and Pi/epp increased.
      Significant correlations were seen between (31)P ratios and Delta[oxCCO]; during
      HI a threshold point was identified where the relationship between Delta[oxCCO]
      and both NTP/epp and Pi/epp changed significantly. Outcome at 48 h related to
      recovery of Delta[oxCCO] and (31)P ratios 1h post-HI (survived: 1-h NTP/epp 0.22
      +/- 0.02, Delta[oxCCO] -0.29 +/- 0.50 MUM; died: 1-h NTP/epp 0.10 +/- 0.04,
      Delta[oxCCO] -2.41 +/- 1.48 MUM). CONCLUSIONS: Both lowered Delta[oxCCO] and
      NTP/epp 1h post-HI indicated mitochondrial impairment. Animals dying before 48 h
      had slower recovery of both Delta[oxCCO] and (31)P ratios by 1 h after HI.

PMID- 23959204
TI  - A novel human enterovirus recombinant from a child with diarrhea.
AB  - Recombination is a well-known phenomenon for enteroviruses. In the present study,
      a novel recombinant HEV-B strain (ChZJ-1) was found in a 2-year-old child with
      diarrhea in Zhenjiang, China. The whole genome of ChZJ-1 was determined.
      Recombination and phylogenetic analysis revealed that ChZJ-1 might have been
      produced by recombination between coxsackievirus B5 and echovirus 18.

PMID- 23959205
TI  - Supramolecular assemblies of bay-substituted perylene diimides in solution and on
      a solid substrate.
AB  - Perylene diimides (PDIs) substituted with a terpyridine moiety at the bay-region
      have been synthesized. These building blocks were used to construct
      supramolecular complexes in chloroform. A dimer and a trimer were built via the
      bay-region complexation with zinc. The PDI compounds were further modified to
      have silane anchors and PDI self-assembled monolayers (SAMs) were prepared on a
      quartz substrate. Complexation of metal ions was also done on the surface, and
      this was observed clearly in the absorption spectrum. These studies on the
      surface show possible progress in the study of supramolecular multilayer
      structures. 

PMID- 23959206
TI  - 3D printed PLA-based scaffolds: a versatile tool in regenerative medicine.
AB  - Rapid prototyping (RP), also known as additive manufacturing (AM), has been well
      received and adopted in the biomedical field. The capacity of this family of
      techniques to fabricate customized 3D structures with complex geometries and
      excellent reproducibility has revolutionized implantology and regenerative
      medicine. In particular, nozzle-based systems allow the fabrication of high
      resolution polylactic acid (PLA) structures that are of interest in regenerative
      medicine. These 3D structures find interesting applications in the regenerative
      medicine field where promising applications including biodegradable templates for
      tissue regeneration purposes, 3D in vitro platforms for studying cell response to
      different scaffolds conditions and for drug screening are considered among
      others. Scaffolds functionality depends not only on the fabrication technique,
      but also on the material used to build the 3D structure, the geometry and inner
      architecture of the structure, and the final surface properties. All being
      crucial parameters affecting scaffolds success. This Commentary emphasizes the
      importance of these parameters in scaffolds' fabrication and also draws the
      attention toward the versatility of these PLA scaffolds as a potential tool in
      regenerative medicine and other medical fields. 

PMID- 23959207
TI  - A randomized controlled trial to assess the effect of self-paced walking on task
      specific anxiety in cardiac rehabilitation patients.
AB  - PURPOSE: Cardiac rehabilitation can reduce overall anxiety. However, task
      specific anxiety is yet to be investigated in the cardiac patient. This study
      investigates the effect of an outdoor walking intervention (WI) in alleviating
      the high degree of task-specific anxiety in cardiac patients. METHODS:
      Participants (N = 22, mean age +/- SD = 62.0 +/- 10.8 years, 9 women), who had
      experienced a cardiac event and exhibited a moderate to high level of anxiety for
      outdoor walking (anxiety score >= 7 on a modified version of the Hospital Anxiety
      and Depression Scale), were initially assessed during an incremental shuttle walk
      test and a self-paced 1-mile walk. Heart rate and the ratings of perceived
      exertion were monitored during both tests. Participants also completed an
      exercise self-efficacy (ESE) questionnaire. Following this, participants were
      randomized to either a 3 sessions per week, 4 weeks, self-paced WI on a
      predetermined variable topographic course, or to a control group (CG; 30-minute
      stationary cycling, 3 sessions per week for 4 weeks). Identical assessments
      (Incremental Shuttle Walk Test, Self-Paced 1-Mile Walk, Hospital Anxiety and
      Depression Scale, ESE) were used postintervention. The 2 groups were compared for
      anxiety, ESE, and fitness by analysis of variance. RESULT: The WI group exhibited
      a significantly greater decrease in task-specific anxiety (51%; P < .01),
      increased self-efficacy (6.6%; P < .001) and improved fitness (P < .05) in
      comparison with CG. CONCLUSION: This study demonstrated that task familiarization
      reduced the task-specific anxiety associated with outdoor walking in cardiac
      patients and, as such, may help in changing exercise behavior patterns in
      patients undergoing cardiac rehabilitation.

PMID- 23959208
TI  - Age-specific normal values for the incremental shuttle walk test in a healthy
      British population.
AB  - PURPOSE: The Incremental Shuttle Walk Test (ISWT) is an important functional and
      prognostic marker in chronic disease. Aging has a detrimental effect on exercise
      performance. The objective of this study was to produce normal age-specific
      values for the ISWT in a healthy British population and to explore whether
      additional variables improve the accuracy of a predictive equation. METHODS:
      Healthy subjects (N = 152), aged 40 to 90 years, were recruited. Data collection
      occurred over 2 study visits. Anthropometric and demographic data were collected,
      and lung function and quadriceps maximal voluntary contraction were measured. An
      accelerometer was worn for 2 consecutive days at home. The Duke Activity Status
      Index was completed, and the greatest distance from 2 ISWTs was recorded.
      RESULTS: One hundred forty subjects (56 men) with mean age (SD) of 59.4 (11.0)
      years completed 2 ISWTs. Forced expiratory volume in 1 second (FEV(1)) was 109.1%
      (14.56%) predicted and ISWT distance was 737 m (183 m). Age-specific normal
      values for the ISWT were observed: mean (lower limit of normal)--40 to 49 years,
      824 m (765 m); 50 to 59 years, 788 m (730 m); 60 to 69 years, 699 m (649 m); and
      70 years and older, 633 m (562 m). A predictive equation was developed from 114
      subjects. Age, body mass index, FEV(1), quadriceps maximal voluntary contraction,
      and Duke Activity Status Index contributed to ISWT distance predicting 50.4% of
      the variation in performance. CONCLUSION: We have developed age-specific normal
      values for performance on the ISWT in a healthy British population. However, even
      using practical, clinically relevant variables, it is not possible to accurately
      predict exercise capacity from a regression equation.

PMID- 23959209
TI  - Effects of different training modalities on circulating anabolic/catabolic
      markers in chronic heart failure.
AB  - BACKGROUND: Muscle wasting in chronic heart failure (CHF) is a result of
      increased catabolism induced by proinflammatory cytokines like tumor necrosis
      factor alpha (TNF-alpha) and interleukin 6 (IL-6), and decreased anabolism due to
      alterations in the insulin-like growth factor 1 (IGF-1)/growth hormone (GH) axis.
      The goal of this study was to analyze the effects of 3 different training
      modalities (endurance training, strength training, and combined strength and
      endurance training [CT]) on circulating cytokines, IGF-1, and GH levels. METHODS:
      Patients with CHF (N = 45), NYHA class II-III, left ventricular ejection fraction
      < 35%, were randomly assigned to 1 of 3 training modalities. They trained for 40
      sessions, 3 times weekly. Fifteen CHF patients served as a control group. Blood
      samples were collected at baseline and 48 hours after the last training session.
      RESULTS: There was a significant decrease in circulating IL-6 with all 3 training
      modalities. Tumor necrosis factor alpha levels decreased in the training groups
      and reached statistical significance for the CT group. No change was observed in
      the control group. There was no difference between the 4 groups. When comparing
      all trained patients with the control group, the decrease in IL-6 was
      significant. Concerning IGF-1 and GH, there was no change with training and no
      change in the control group. CONCLUSION: Exercise training has no effects on
      circulating IGF-1 and GH. The decreases in cytokines are evident only when all
      trained patients are compared with the control group, independently of the
      modality of training intervention.

PMID- 23959210
TI  - The near-mid-IR HOMO-LUMO gap in amide linked porphyrin-rhodamine dyads.
AB  - Novel amide linked porphyrin-rhodamine dyads yield utmost intense red-shifted
      electronic transitions beyond the near-infrared region. 

PMID- 23959211
TI  - Layered Li2MnO3.3LiNi(0.5-x)Mn(0.5-x)Co(2x)O2 microspheres with Mn-rich cores as
      high performance cathode materials for lithium ion batteries.
AB  - Layered Li2MnO3.3LiNi0.5-xMn0.5-xCo2xO2 (x = 0, 0.05, 0.1, 0.165) microspheres
      with Mn-rich core were successfully synthesized by a simple two-step
      precipitation calcination method and intensively evaluated as cathode materials
      for lithium ion batteries. The X-ray powder diffractometry (XRD) results indicate
      that the growth of Li2MnO3-like regions is impeded due to the presence of cobalt
      (Co) in the material. The field-emission scanning electron microscopy (FESEM)
      data reveal the core-shell-like structure with a Mn-rich core in the as-prepared
      particles. The charge-discharge testing reveals that the capacity is markedly
      improved by adding Co. The activation of the cathode after Co doping becomes
      easier and can be accomplished completely when charged to 4.6 V at the C/40 rate
      in the initial cycle. Superior electrochemical performances are obtained for
      samples with x = 0.05 and 0.1. The corresponding initial discharge capacities are
      separately 281 and 285 mA h g(-1) at C/40 between 2 and 4.6 V at room
      temperature. After 250 cycles at C/2, the respective capacity retentions are
      71.2% and 70.4%, which are better compared to the normal Li-excess
      Li2MnO3.3LiNi0.4Mn0.4Co0.2O2 sample with a uniform distribution of Mn element in
      the particles. The initial discharge capacities of both samples are approximately
      250 mA h g(-1) at a rate of C/2 between 2 and 4.6 V at 55  degrees C after
      activation. Furthermore, the samples are investigated by electrochemical
      impedance spectroscopy (EIS) at room and elevated temperature, revealing that the
      key factor affecting electrochemical performance is the charge transfer
      resistance in the particles. 

PMID- 23959212
TI  - Neuronostatin ameliorates sodium taurocholate-induced acute pancreatitis in rats.
AB  - BACKGROUND AND AIMS: Neuronostatin is encoded in the preprosomatostatin gene and
      exerts important physiological actions on neuronal and cardiovascular regulation
      and metabolism in diverse tissues. An intraperitoneal injection of neuronostatin
      can induce c-Jun expression in the periphery of pancreatic islets. Because of the
      relatively high amount of neuronostatin present in the pancreas, it is necessary
      to investigate the effects of neuronostatin on pancreas. Furthermore, little is
      known about the effect of neuronostatin on acute pancreatitis. METHODS:
      Neuronostatin (30, 60, and 120 nmol) was injected in to the external jugular vein
      30 min before retrograde infusion of 2 % sodium taurocholate into the
      pancreaticobiliary duct. After 6 h, histological damage of the pancreas was
      evaluated by pancreas weight and paraffin section. A blood sample was collected
      to determine the serum amylase and lipase activities. RESULTS: In our findings,
      neuronostatin groups had a reduction in interstitial edema, acinar cell
      vacuolization, and inflammatory infiltration of the pancreas compared with the
      model group. Biochemical data showed that serum amylase and lipase activities
      were significantly decreased in neuronostatin-pretreated groups by comparison
      with the model group. CONCLUSIONS: Histopathologic examination suggests that
      neuronostatin ameliorated the histological damage of sodium taurocholate-induced
      acute pancreatitis in rats. The biochemical analysis was consistent with that
      obtained from histopathologic examination, which was toward a trend of
      attenuating acute pancreatitis. In summary, neuronostatin might be potentially
      capable of ameliorating pancreatic damage in acute pancreatitis in rats.

PMID- 23959213
TI  - Pain and opioid use in chronic liver disease: optimal treatment must address the
      mental health care needs of the patient.

PMID- 23959214
TI  - Salience network resting-state activity: prediction of frontotemporal dementia
      progression.
AB  - IMPORTANCE: Noninvasive measures of activity within intrinsic brain networks may
      be clinically relevant, providing a marker of neurodegenerative disease and
      predicting clinical behaviors. OBJECTIVE: To correlate baseline resting-state
      measures within the salience network and changes in behavior among patients with
      frontotemporal dementia. DESIGN: Baseline resting-state functional magnetic
      resonance imaging data and longitudinal clinical measures were obtained from
      prospectively accrued patients during 8 weeks. SETTING: Tertiary academic care
      center specializing in the assessment and management of patients with
      neurodegenerative disease. PARTICIPANTS: Fifteen patients with clinically
      diagnosed frontotemporal dementia (5 behavioral variant and 10 semantic
      dementia). MAIN OUTCOMES AND MEASURES: Baseline resting-state functional magnetic
      resonance imaging data measured within regions of interest were regressed on
      serial behavioral measures from prospectively accrued patients with
      frontotemporal dementia to determine the ability of baseline resting-state
      activity to account for changes in behavior. RESULTS: Low-frequency fluctuations
      in the left insula significantly predicted changes in Frontal Behavioral
      Inventory scores (standard beta = 0.51, P = .049), accounting for 28% of the
      change variance. The trend was driven by changes in measures of apathy
      independent of dementia severity. CONCLUSION AND RELEVANCE: Baseline measures of
      salience network connectivity involving the left insula may predict behavioral
      changes in patients with frontotemporal dementia.

PMID- 23959215
TI  - The impact of solution chemistry of electrolyte on the sorption of
      pentachlorophenol and phenanthrene by natural hematite nanoparticles.
AB  - Hematite nanoparticles (NPs) were studied as a sorbent for hydrophobic organic
      contaminants (OCs) under natural ambient conditions through specially designed
      contrasting solution chemistry of electrolyte. Ionizable pentachlorophenol (PCP)
      and non-ionizable phenanthrene (PHE) were selected as representative OCs. The
      sorption capacities of PCP and PHE were pH-dependent, and a larger amount of PCP
      was sorbed at pH values below its pKa (4.75). However, the PHE sorption capacity
      was higher at relatively high or low pHs (e.g. below 4.0 and above 10.0),
      possibly due to the larger available surface area of the hematite NPs, caused by
      the higher values of net charges and charge density. Changes in pH might thus
      affect the sorption of OCs by hematite NPs, through modification of the surface
      characteristics of the sorbent and the electronic properties of the sorbate
      molecules. The influence of different ionic strengths indicated that the amounts
      of PCP and PHE sorbed by hematite NPs decreased as a concentration function of
      different types of ions (e.g. Na(+), K(+), Mg(2+) and Ca(2+)), with the
      underlying mechanism possibly being due to four interactions i.e. hydrogen
      bonding, competitive sorption by ions in the ambient solution, screening effects
      and aggregation effects. The results confirmed that the surface chemistry of
      hematite NPs, the chemical properties of PCP and PHE, and solution chemistry
      (e.g. pH and ionic strength) of the electrolyte all played an important role in
      PCP and PHE sorption by hematite NPs. By comparison of both sorption capacity and
      ecologic advantages, our results suggested that natural hematite NPs would be
      more competitive and efficient for PCP and PHE sorption than engineered NPs. This
      finding increases our knowledge regarding the environmental function of natural
      NPs (such as hematite NPs) for OC remediation through manipulating their
      interfacial behavior. 

PMID- 23959216
TI  - The human body burden of polybrominated diphenyl ethers and their relationships
      with thyroid hormones in the general population in Northern China.
AB  - This study was conducted to determine the human body burden of polybrominated
      diphenyl ethers (PBDEs) and then clarify the relationships between that and the
      disruption of thyroid hormones in the general population in Northern China.
      Between November 2010 and May 2011, 124 serum samples were obtained from
      volunteers from the provinces of Shanxi and Liaoning. Serum samples were prepared
      by solid-phase extraction and analyzed for BDE-17, 28, 47, 66, 99, 100, 153, 154,
      183 and 209 by gas chromatography-negative chemical ionization mass spectrometry.
      The median concentration of the total PBDEs was 7.2 ng/g lipid weights (lw);
      concentrations ranged from 2.1 to 160.3 ng/glw. The PBDE profiles in this study
      differed from those of other general populations. BDE-209 was the most abundant
      congener (median, 5.0 ng/glw; range, non-detected - 157.1 ng/glw), accounting for
      more than 75% of the total PBDEs, followed by BDE-153. The total PBDE
      concentrations in men were significantly higher as compared to women. The donors'
      age was correlated with a few PBDE congeners, but was not correlated with the
      total PBDE concentrations. The overall level of PBDEs in this study was lower
      than that observed in general populations in Southern China, Europe, and North
      America. There were apparent correlations between concentrations of several PBDE
      congeners and thyroid hormones. Triiodothyronine (T3) was correlated with BDE-99
      and 209 and inversely correlated with BDE-17, 28, 47, 153, 183, and the summed
      tri- to hepta-PBDE congeners (?3-7PBDEs). Thyroid-stimulating hormone (TSH) was
      correlated with BDE-17, 28, 47, and 183 and inversely correlated with BDE-99. No
      correlation between free tetraidothyronine (FT4) and PBDEs was observed. Logistic
      regression analysis results indicated that those with higher levels of BDE-17 or
      BDE-153 had significantly lower odds of having T3 levels above the normal range
      compared to those with lower levels of BDE-17 or BDE-153. Association between FT4
      and BDE-153 disappeared after controlling for sex and age. However, there was no
      significant association between TSH and PBDEs. The results of the present study
      showed that even at a relatively low level, PBDEs might interfere with the
      thyroid hormone levels in the general population.

PMID- 23959217
TI  - Balancing effluent quality, economic cost and greenhouse gas emissions during the
      evaluation of (plant-wide) control/operational strategies in WWTPs.
AB  - The objective of this paper was to show the potential additional insight that
      result from adding greenhouse gas (GHG) emissions to plant performance evaluation
      criteria, such as effluent quality (EQI) and operational cost (OCI) indices, when
      evaluating (plant-wide) control/operational strategies in wastewater treatment
      plants (WWTPs). The proposed GHG evaluation is based on a set of comprehensive
      dynamic models that estimate the most significant potential on-site and off-site
      sources of CO2, CH4 and N2O. The study calculates and discusses the changes in
      EQI, OCI and the emission of GHGs as a consequence of varying the following four
      process variables: (i) the set point of aeration control in the activated sludge
      section; (ii) the removal efficiency of total suspended solids (TSS) in the
      primary clarifier; (iii) the temperature in the anaerobic digester; and (iv) the
      control of the flow of anaerobic digester supernatants coming from sludge
      treatment. Based upon the assumptions built into the model structures, simulation
      results highlight the potential undesirable effects of increased GHG production
      when carrying out local energy optimization of the aeration system in the
      activated sludge section and energy recovery from the AD. Although off-site CO2
      emissions may decrease, the effect is counterbalanced by increased N2O emissions,
      especially since N2O has a 300-fold stronger greenhouse effect than CO2. The
      reported results emphasize the importance and usefulness of using multiple
      evaluation criteria to compare and evaluate (plant-wide) control strategies in a
      WWTP for more informed operational decision making.

PMID- 23959218
TI  - Spatial and seasonal variabilities of dissolved hydrocarbons in surface waters
      from the Northwestern Mediterranean Sea: results from one year intensive
      sampling.
AB  - Dissolved aliphatic hydrocarbons (AHs) and polycyclic aromatic hydrocarbons
      (PAHs) were analysed from surface water collected in continental, harbour and off
      shore marine sites from Marseilles coastal area (Northwestern Mediterranean Sea)
      from February 2011 to February 2012. AH and PAH concentrations were in the range
      of 0.04-0.53 MUgl(-1) and 8.1-405 ngl(-1), respectively. They both displayed
      seasonal and spatial variations in their concentrations and molecular
      composition. The lowest AH concentrations were found in summer and the highest
      PAH concentrations in winter. Both natural and anthropogenic (pyrogenic and
      petrogenic) hydrocarbon sources were identified. In winter, concentrations and
      composition patterns highlighted an increase in the signature of unburned and
      combusted fossil fuels, while they suggested an enhancement of weathering
      processes in summer months. Hydrocarbon inputs to the dissolved phase seemed to
      originate mainly from the atmosphere and the Rhone River. Hydrocarbon additional
      sources were identified only at the harbour site, emphasising the intense
      shipping traffic and industrial activities occurring in one of the most important
      Mediterranean harbours. This study underscores the strong dynamics of dissolved
      hydrocarbons and the uncoupling of the sources, transport and removing processes
      affecting AHs and PAHs. It also demonstrates the pertinence of taking this
      dynamics into account for the budget assessments of organic pollutants in coastal
      environments.

PMID- 23959219
TI  - Effect of long term organic amendments and vegetation of vineyard soils on the
      microscale distribution and biogeochemistry of copper.
AB  - In this study we evaluated the effect of the long term organic management of a
      vineyard-soil on the biogeochemistry of copper at the micro-aggregate scale. The
      model vineyard-soil (Macon-France) experienced a long-term field-experiment that
      consisted in amendments and vegetations with various materials and plants. We
      studied specifically the effect of Straw (S) and Conifer Compost (CC) organic
      amendments and Clover (Cl) and Fescue (F) vegetation on the fate of copper
      (fungicide) in the surface layer of this loamy soil, through a comparison with
      the Non Amended soil (NA). After collection the five soils were immediately
      physically fractionated in order to obtain 5 granulometric size-fractions. All
      soils and size-fractions were quantitatively characterized in terms of
      granulometry, chemical content and copper distribution, speciation and
      bioavailability to bacteria and plants. The results showed strong increases of
      soil-constituents aggregation for all treatments (Cl>CC>S>F>NA), in relation with
      the increased cementation of soil-constituents by organic matter (OM). The
      distribution patterns of all major elements and organic carbon were found highly
      variable within the soil sub-fractions and also between the 5 treatments. Due to
      their specific inorganic and organic composition, soil sub-fractions can thus be
      considered as a specific microbial habitat. Added OM accumulated preferentially
      in the 20-2 MUm and in the >250 MUm of the 5 soils. The distribution patterns of
      copper as well as its speciation and bioavailability to bacteria in the soil sub
      fractions were shown to be strongly different among the five soils, in relation
      with OM distribution. Our results also suggest that Cu-bioavailability to plants
      is controlled by soil-rhizosphere structure. Altogether our results permitted to
      show that long-term organic management of a vineyard soil induced stable
      modifications of soil physical and chemical properties at both macro and micro
      scales. These modifications affected in turn the micro-scale biogeochemistry of
      copper, and especially its bioavailability to bacteria and plants.

PMID- 23959220
TI  - Trophic transfer of polychlorinated biphenyls (PCB) in a boreal lake ecosystem:
      testing of bioaccumulation models.
AB  - Understanding the fate of persistent organic chemicals in the environment is
      fundamental information for the successful protection of ecosystems and humans. A
      common dilemma in risk assessment is that monitoring data reveals contaminant
      concentrations in wildlife, while the source concentrations, route of uptake and
      acceptable source concentrations remain unsolved. To overcome this problem,
      different models have been developed in order to obtain more precise risk
      estimates for the food webs. However, there is still an urgent need for studies
      combining modelled and measured data in order to verify the functionality of the
      models. Studies utilising field-collected data covering entire food webs are
      particularly scarce. This study aims to contribute to tackling this problem by
      determining the validity of two bioaccumulation models, BIOv1.22 and AQUAWEBv1.2,
      for application to a multispecies aquatic food web. A small boreal lake, Lake
      Kernaalanjarvi, in Finland was investigated for its food web structure and
      concentrations of PCBs in all trophic levels. Trophic magnification factors
      (TMFs) were used to measure the bioaccumulation potential of PCBs, and the site
      specific environmental parameters were used to compare predicted and observed
      concentrations. Site-specific concentrations in sediment pore water did not
      affect the modelling endpoints, but accurate site-specific measurements of freely
      dissolved concentrations in water turned out to be crucial for obtaining
      realistic model-predicted concentrations in biota. Numerous parameters and
      snapshot values affected the model performances, bringing uncertainty into the
      process and results, but overall, the models worked well for a small boreal lake
      ecosystem. We suggest that these models can be optimised for different ecosystems
      and can be useful tools for estimating the bioaccumulation and environmental fate
      of PCBs. 

PMID- 23959221
TI  - Chronic plantar fasciitis: plantar fasciotomy versus gastrocnemius recession.
AB  - PURPOSE: The purpose of this study was to compare results of partial proximal
      fasciotomy (PPF) with proximal medial gastrocnemius release (PMGR) in the
      treatment of chronic plantar fasciitis (CPF). METHOD: This retrospective study
      compares 30 patients with CPF that underwent PPF with 30 that underwent isolated
      PMGR. Both groups were matched in terms of previous treatments and time from
      onset of symptoms to surgery. Different standardised evaluation scales (VAS,
      Likert, AOFASh) were used to evaluate results. RESULTS: Plantar fasciotomy had
      satisfactory results in just 60 % of patients, with an average ten weeks needed
      to resume work and sports. Patient satisfaction in the PMGR group reached 95 %,
      being back to work and sports at three weeks on average. Functional and pain
      scores were considerably better for PMGR and fewer complications registered.
      CONCLUSION: In our series, isolated PMGR is a simple and reliable procedure to
      treat patients with CPF. It provides far better results than conventional
      fasciotomy with less morbidity and better patient satisfaction, and thus has
      become our surgical procedure of choice in recalcitrant CPF.

PMID- 23959222
TI  - Supramalleolar osteotomies for degenerative joint disease of the ankle joint:
      indication, technique and results.
AB  - Patients with varus or valgus hindfoot deformities usually present with
      asymmetric ankle osteoarthritis. In-vitro biomechanical studies have shown that
      varus or valgus hindfoot deformity may lead to altered load distribution in the
      tibiotalar joint which may result in medial (varus) or lateral (valgus)
      tibiotalar joint degeneration in the short or medium term. The treatment of
      asymmetric ankle osteoarthritis remains challenging, because more than half of
      the tibiotalar joint surface is usually preserved. Therefore, joint-sacrificing
      procedures like total ankle replacement or ankle arthrodesis may not be the most
      appropriate treatment options. The shortand midterm results following realignment
      surgery, are very promising with substantial pain relief and functional
      improvement observed post-operatively. In this review article we describe the
      indications, surgical techniques, and results from of realignment surgery of the
      ankle joint in the current literature.

PMID- 23959223
TI  - Functional outcome following a locked fracture-dislocation of the calcaneus.
AB  - PURPOSE: Locked fracture-dislocations of the calcaneus are uncommon, and a
      substantial number of these injuries is not recognised or is misdiagnosed at
      first presentation. The primary aim of this study was to evaluate the long-term
      outcome in patients with this injury. METHODS: This is a retrospective cohort
      study of adult patients who sustained a uni- or bilateral calcaneal
      fracturedislocation. Outcome was measured using validated questionnaires,
      including the American Orthopaedic Foot and Ankle Society Hindfoot score (AOFAS),
      Foot Function Index (FFI) and a visual analogue scale (VAS). RESULTS: During the
      12-year study period a total of 16 patients with 17 locked fracture-dislocations
      were identified. This represented 6 % of all surgically treated calcaneal
      fractures (17 of 279). The median follow-up was 48 months. All patients were
      treated using an extended lateral approach and plate fixation. In one patient
      with a delayed presentation a primary arthrodesis was performed. The functional
      outcome scores were available for 14 patients with 14 fractures. The median AOFAS
      was 74 [interquartile range (IQR) 47-86], the median FFI was 18 (IQR 6-37) and
      the median VAS for overall satisfactionwas 8.2 (IQR 5.5-9.4). A secondary fusion
      was deemed necessary in three cases. CONCLUSIONS: This study shows that, with
      surgical treatment via an extended lateral approach, the outcome in patients with
      a locked fracture-dislocation of the calcaneus is similar to the outcome of other
      displaced intra-articular calcaneal fracture types. However, a higher rate of
      secondary subtalar fusion can be expected.

PMID- 23959224
TI  - Occlusion of the retinal artery occlusion by undiagnosed accessory mitral valve
      tissue.

PMID- 23959226
TI  - Vascular disease: Peripheral artery disease pandemic.

PMID- 23959225
TI  - Discovery of a potent benzoxaborole-based anti-pneumococcal agent targeting
      leucyl-tRNA synthetase.
AB  - Streptococcus pneumoniae causes bacterial pneumonia with high mortality and
      morbidity. The emergency of multidrug-resistant bacteria threatens the treatment
      of the disease. Leucyl-tRNA synthetase (LeuRS) plays an essential role in
      cellular translation and is an attractive drug target for antimicrobial
      development. Here we report the compound ZCL039, a benzoxaborole-based derivative
      of AN2690, as a potent anti-pneumococcal agent that inhibits S. pneumoniae LeuRS
      (SpLeuRS) activity. We show using kinetic, biochemical analyses combined with the
      crystal structure of ZCL039-AMP in complex with the separated SpLeuRS editing
      domain, that ZCL039 binds to the LeuRS editing active site which requires the
      presence of tRNA(Leu), and employs an uncompetitive inhibition mechanism. Further
      docking models establish that ZCL039 clashes with the eukaryal/archaeal specific
      insertion I4ae helix within editing domains. These findings demonstrate the
      potential of benzoxaboroles as effective LeuRS inhibitors for pneumococcus
      infection therapy, and provide future structure-guided drug design and
      optimization. 

PMID- 23959227
TI  - Matrix metalloproteinases in right ventricular failure.

PMID- 23959228
TI  - Targeting RV failure and cardiomyocyte injury in acute pulmonary thromboembolism.

PMID- 23959230
TI  - Chirality-specific hydrolysis of amino acid substrates by cellulose nanofibers.
AB  - We demonstrate for the first time that cellulose nanofibers obtained from natural
      sources have the capability to hydrolyze the amide bonds of amino acid substrates
      in a chirality-specific manner. The chiral specificities were clearly correlated
      with the species of amino acid units and the crystal structures of cellulose. 

PMID- 23959229
TI  - Pharmacotherapies for lipid modification: beyond the statins.
AB  - The widespread clinical use of statins has contributed to significant reductions
      in the rate of cardiovascular morbidity and mortality over the past 3 decades,
      and statins are considered first-line therapy for the prevention and treatment of
      atherosclerotic vascular disease. Nevertheless, various other lipid-lowering
      agents can provide clinical benefit by supplementing or augmenting statin therapy
      in patients with severe hypercholesterolaemia or mixed dyslipidaemia, or by
      providing an alternative for patients who are intolerant to statins. Bile acid
      resins and niacin were prescribed for lipid modification for years before the
      introduction of the statins, and new data continue to emerge regarding their use
      in different patient groups and for specific conditions. Ezetimibe can be
      appropriate for patients whose primary lipid abnormality is an elevated LDL
      cholesterol level, whereas the fibrates seem to be most beneficial in patients
      with low levels of HDL cholesterol and elevated triglycerides. At the end of 2012
      and the beginning of 2013, the first microsomal triglyceride transfer protein
      inhibitor, lomitapide, and the first antisense therapy to target apolipoprotein
      B, mipomersen, were approved for the treatment of individuals with extremely
      elevated LDL-cholesterol levels caused by homozygous familial
      hypercholesterolaemia. Although two agents in the experimental class of
      cholesteryl ester transfer protein inhibitors have failed to show a benefit in
      clinical trials, newer drugs in this class could provide an additional strategy
      to address residual cardiovascular risk in patients treated with statins. 

PMID- 23959231
TI  - The influence of coupling agents on mechanical property retention and long-term
      cytocompatibility of phosphate glass fibre reinforced PLA composites.
AB  - Completely resorbable composites are an attractive alternative for metallic bone
      fracture fixation devices. However, failure of their interfacial integrity within
      aqueous environments, which can lead to a rapid loss of overall mechanical
      properties, has been reported in the literature. In this study coupling agents
      were investigated for phosphate glass fibre reinforced poly(lactic acid)
      composites. Three coupling agents with varying wettability were employed to
      improve initial mechanical properties and their retention in vitro via
      improvement of the interfacial bond between polymer matrix and fibres. Coupling
      agents were grafted onto the glass fibres by dip-coating in coupling agent
      solution at optimised concentrations. Three-aminopropyltriethoxy silane and
      sorbitol ended PLA oligomer treatments improved the initial flexural properties
      (27% strength with APS and 17% modulus via SPLA treatment) of the composites and
      3-aminopropyltriethoxy silane and hexamethylene diisocyanate (HDI) treatments
      also decreased the loss of flexural strength and modulus during degradation. HDI
      treated samples retained 57.2% and 64.7% of their initial strength and modulus,
      respectively compared to control where only 34% of initial strength and 52% of
      initial modulus was retained after 28 days of degradation in PBS solution.
      Initial improvements in flexural properties were associated with improved shear
      bond strength at the interface due to covalent bonding between the glass fibres
      and polymer matrix provided by the coupling agents. Delay in mechanical property
      loss with degradation was suggested to be due to the hydrophobicity at the
      interface, which could have hindered the interfacial integrity loss and
      consequently loss of mechanical integrity of the composites. All coupling agent
      treated and control composites were tested for cytocompatibility using a primary
      human osteoblast cell line. A comparable response to the control, in terms of
      cell adhesion, proliferation and differentiation was observed supporting the use
      of these agents within implantable devices. 

PMID- 23959232
TI  - Low calcium intake is associated with high plasma homocysteine levels in
      postmenopausal women.
AB  - Nutritional interventions targeting homocysteine remain controversial, and
      further nutritional research is warranted. We thus sought to explore the
      determinants of plasma homocysteine other than B-group vitamins. This cross
      sectional study surveyed the nutritional status of 713 Japanese postmenopausal
      women using a semiquantitative food frequency questionnaire. Associations between
      total energy, protein, fat, carbohydrate, and vitamin A and K intakes and
      homocysteine were insignificant. Mean homocysteine in the second (536.1 +/- 34.7
      mg/day) and third (712.9 +/- 115.6 mg/day) tertiles of calcium intake were lower
      than in the first tertile (379.6 +/- 76.6 mg/day) by -0.57 nmol/mL (95 %
      confidence interval, -1.10 to-0.04, p = 0.04) and -1.18 nmol/mL (-1.76 to -0.60,
      p<0.01), respectively, after adjustment for lifestyle and clinical factors (trend
      p?0.01). Mean homocysteine in those with dietary calcium intake above the median
      (>536 mg/day) were lower regardless of the folic acid concentration; the
      differences were -1.59 nmol/mL (-2.33 to -0.85, p = 0.02) and -0.75 nmol/mL (
      1.37 to-0.12, p<0.01) for the high (<7.8 ng/mL) and low folic acid groups,
      respectively. There was no significant association between calcium and folic acid
      (p = 0.08). In conclusion, further prospective research to confirm our findings
      is needed for the development of nutritional inventions targeting homocysteine.

PMID- 23959234
TI  - A semi-quantitative model of Quorum-Sensing in Staphylococcus aureus, approved by
      microarray meta-analyses and tested by mutation studies.
AB  - Staphylococcus aureus (SA) causes infections including severe sepsis by
      antibiotic-resistant strains. It forms biofilms to protect itself from the host
      and antibiotics. Biofilm and planktonic lifestyle are regulated by a complex
      quorum sensing system (QS) with the central regulator agr. To study biofilm
      formation and QS we set up a Boolean node interaction network (94 nodes, 184
      edges) that included different two component systems such as agr, sae and arl.
      Proteins such as sar, rot and sigB were included. Each gene node represents the
      resulting activity of its gene products (mRNA and protein). Network consistency
      was tested according to previous knowledge and the literature. Regulator mutation
      combinations (agr-, sae-, sae-/agr-, sigB+, sigB+/sae-) were tested in silico in
      the model and compared regarding system changes and responses to experimental
      gene expression data. High connectivity served as a guide to identify master
      regulators, and their detailed behaviour was studied both in vitro and in the
      model. System analysis showed two stable states, biofilm forming versus
      planktonic, with clearly different sub-networks turned on. Predicted node
      activity changes from the in silico model were in line with microarray gene
      expression data of different knockout strains. Additional in silico predictions
      about node activity and biofilm formation were compared to new in vitro
      experiments (northern blots and biofilm adherence assays) which confirmed these.
      Further experiments in silico as well as in vitro showed the sae locus as the
      central modulator of biofilm production. Sae knockout strains showed stronger
      biofilms. Wild type phenotype was rescued by sae complementation. The in silico
      network provides a theoretical model that agrees well with the presented
      experimental data on how integration of different inputs is achieved in the QS of
      SA. It faithfully reproduces the behaviour of QS mutants and their biofilm
      forming ability and allows predictions about mutations and mutation combinations
      for any node in the network. The model and simulations allow us to study QS and
      biofilm formation in SA including behaviour of MRSA strains and mutants. The in
      vitro and in silico evidence stresses the role of sae and agr in fine-tuning
      biofilm repression and/or SA dissemination.

PMID- 23959233
TI  - Cardiovascular autophagy: concepts, controversies, and perspectives.
AB  - Despite recent scientific and technological advances, cardiovascular disease
      remains the leading cause of morbidity and mortality worldwide. Autophagy, an
      evolutionarily ancient response to cellular stress, has been implicated in the
      pathogenesis of a wide range of heart pathologies. However, the precise role of
      autophagy in these contexts remains obscure owing to its multifarious actions.
      Here, we review recently derived insights regarding the role of autophagy in
      multiple manifestations of cardiac plasticity and disease. 

PMID- 23959235
TI  - Optimal sensor placement for multiple target positioning with range-only
      measurements in two-dimensional scenarios.
AB  - The problem of determining the optimal geometric configuration of a sensor
      network that will maximize the range-related information available for multiple
      target positioning is of key importance in a multitude of application scenarios.
      In this paper, a set of sensors that measures the distances between the targets
      and each of the receivers is considered, assuming that the range measurements are
      corrupted by white Gaussian noise, in order to search for the formation that
      maximizes the accuracy of the target estimates. Using tools from estimation
      theory and convex optimization, the problem is converted into that of maximizing,
      by proper choice of the sensor positions, a convex combination of the logarithms
      of the determinants of the Fisher Information Matrices corresponding to each of
      the targets in order to determine the sensor configuration that yields the
      minimum possible covariance of any unbiased target estimator. Analytical and
      numerical solutions are well defined and it is shown that the optimal
      configuration of the sensors depends explicitly on the constraints imposed on the
      sensor configuration, the target positions, and the probabilistic distributions
      that define the prior uncertainty in each of the target positions. Simulation
      examples illustrate the key results derived. 

PMID- 23959236
TI  - Light-addressed electrodeposition of enzyme-entrapped chitosan membranes for
      multiplexed enzyme-based bioassays using a digital micromirror device.
AB  - This paper describes a light-addressed electrolytic system used to perform an
      electrodeposition of enzyme-entrapped chitosan membranes for multiplexed enzyme
      based bioassays using a digital micromirror device (DMD). In this system, a
      patterned light illumination is projected onto a photoconductive substrate
      serving as a photo-cathode to electrolytically produce hydroxide ions, which
      leads to an increased pH gradient. The high pH generated at the cathode can cause
      a local gelation of chitosan through sol-gel transition. By controlling the
      illumination pattern on the DMD, a light-addressed electrodeposition of chitosan
      membranes with different shapes and sizes, as well as multiplexed
      micropatterning, was performed. The effect of the illumination time of the light
      pattern on the dimensional resolution of chitosan membrane formation was examined
      experimentally. Moreover, multiplexed enzyme-based bioassay of enzyme-entrapped
      chitosan membranes was also successfully demonstrated through the
      electrodeposition of the chitosan membranes with various shapes/sizes and
      entrapping different enzymes. As a model experiment, glucose and ethanol were
      simultaneously detected in a single detection chamber without cross-talk using
      shape-coded chitosan membranes entrapped with glucose oxidase (GOX), peroxidase
      (POD), and Amplex Red (AmR) or alcohol oxidase (AOX), POD, and AmR by using same
      fluorescence indicator (AmR). 

PMID- 23959237
TI  - Assessing temporal stability for coarse scale satellite moisture validation in
      the Maqu area, Tibet.
AB  - This study evaluates if the temporal stability concept is applicable to a time
      series of satellite soil moisture images so to extend the common procedure of
      satellite image validation. The area of study is the Maqu area, which is located
      in the northeastern part of the Tibetan plateau. The network serves validation
      purposes of coarse scale (25-50 km) satellite soil moisture products and
      comprises 20 stations with probes installed at depths of 5, 10, 20, 40, 80 cm.
      The study period is 2009. The temporal stability concept is applied to all five
      depths of the soil moisture measuring network and to a time series of satellite
      based moisture products from the Advance Microwave Scanning Radiometer (AMSR-E).
      The in-situ network is also assessed by Pearsons's correlation analysis.
      Assessments by the temporal stability concept proved to be useful and results
      suggest that probe measurements at 10 cm depth best match to the satellite
      observations. The Mean Relative Difference plot for satellite pixels shows that a
      RMSM pixel can be identified but in our case this pixel does not overlay any in
      situ station. Also, the RMSM pixel does not overlay any of the Representative
      Mean Soil Moisture (RMSM) stations of the five probe depths. Pearson's
      correlation analysis on in-situ measurements suggests that moisture patterns over
      time are more persistent than over space. Since this study presents first results
      on the application of the temporal stability concept to a series of satellite
      images, we recommend further tests to become more conclusive on effectiveness to
      broaden the procedure of satellite validation. 

PMID- 23959238
TI  - PEDOT:PSS-based piezo-resistive sensors applied to reinforcement glass fibres for
      in situ measurement during the composite material weaving process.
AB  - The quality of fibrous reinforcements used in composite materials can be
      monitored during the weaving process. Fibrous sensors previously developed in our
      laboratory, based on PEDOT:PSS, have been adapted so as to directly measure the
      mechanical stress on fabrics under static or dynamic conditions. The objective of
      our research has been to develop new sensor yarns, with the ability to locally
      detect mechanical stresses all along the warp or weft yarn. This local detection
      is undertaken inside the weaving loom in real time during the weaving process.
      Suitable electronic devices have been designed in order to record in situ
      measurements delivered by this new fibrous sensor yarn. 

PMID- 23959239
TI  - Digital pixel sensor array with logarithmic delta-sigma architecture.
AB  - Like the human eye, logarithmic image sensors achieve wide dynamic range easily
      at video rates, but, unlike the human eye, they suffer from low peak signal-to
      noise-and-distortion ratios (PSNDRs). To improve the PSNDR, we propose
      integrating a delta-sigma analog-to-digital converter (ADC) in each pixel. An
      image sensor employing this architecture is designed, built and tested in 0.18
      micron complementary metal-oxide-semiconductor (CMOS) technology. It achieves a
      PSNDR better than state-of-the-art logarithmic sensors and comparable to the
      human eye. As the approach concerns an array of many ADCs, we use a small-area
      low-power delta-sigma design. For scalability, each pixel has its own decimator.
      The prototype is compared to a variety of other image sensors, linear and
      nonlinear, from industry and academia. 

PMID- 23959240
TI  - Automatic and direct identification of blink components from scalp EEG.
AB  - Eye blink is an important and inevitable artifact during scalp
      electroencephalogram (EEG) recording. The main problem in EEG signal processing
      is how to identify eye blink components automatically with independent component
      analysis (ICA). Taking into account the fact that the eye blink as an external
      source has a higher sum of correlation with frontal EEG channels than all other
      sources due to both its location and significant amplitude, in this paper, we
      proposed a method based on correlation index and the feature of power
      distribution to automatically detect eye blink components. Furthermore, we prove
      mathematically that the correlation between independent components and scalp EEG
      channels can be translating directly from the mixing matrix of ICA. This helps to
      simplify calculations and understand the implications of the correlation. The
      proposed method doesn't need to select a template or thresholds in advance, and
      it works without simultaneously recording an electrooculography (EOG) reference.
      The experimental results demonstrate that the proposed method can automatically
      recognize eye blink components with a high accuracy on entire datasets from 15
      subjects. 

PMID- 23959241
TI  - A novel gaze tracking method based on the generation of virtual calibration
      points.
AB  - Most conventional gaze-tracking systems require that users look at many points
      during the initial calibration stage, which is inconvenient for them. To avoid
      this requirement, we propose a new gaze-tracking method with four important
      characteristics. First, our gaze-tracking system uses a large screen located at a
      distance from the user, who wears a lightweight device. Second, our system
      requires that users look at only four calibration points during the initial
      calibration stage, during which four pupil centers are noted. Third, five
      additional points (virtual pupil centers) are generated with a multilayer
      perceptron using the four actual points (detected pupil centers) as inputs.
      Fourth, when a user gazes at a large screen, the shape defined by the positions
      of the four pupil centers is a distorted quadrangle because of the nonlinear
      movement of the human eyeball. The gaze-detection accuracy is reduced if we map
      the pupil movement area onto the screen area using a single transform function.
      We overcame this problem by calculating the gaze position based on multi
      geometric transforms using the five virtual points and the four actual points.
      Experiment results show that the accuracy of the proposed method is better than
      that of other methods. 

PMID- 23959242
TI  - A review of methods for sensing the nitrogen status in plants: advantages,
      disadvantages and recent advances.
AB  - Nitrogen (N) plays a key role in the plant life cycle. It is the main plant
      mineral nutrient needed for chlorophyll production and other plant cell
      components (proteins, nucleic acids, amino acids). Crop yield is affected by
      plant N status. Thus, the optimization of nitrogen fertilization has become the
      object of intense research due to its environmental and economic impact. This
      article focuses on reviewing current methods and techniques used to determine
      plant N status. Kjeldahl digestion and Dumas combustion have been used as
      reference methods for N determination in plants, but they are destructive and
      time consuming. By using spectroradiometers, reflectometers, imagery from
      satellite sensors and digital cameras, optical properties have been measured to
      estimate N in plants, such as crop canopy reflectance, leaf transmittance,
      chlorophyll and polyphenol fluorescence. High correlation has been found between
      optical parameters and plant N status, and those techniques are not destructive.
      However, some drawbacks include chlorophyll saturation, atmospheric and soil
      interference, and the high cost of instruments. Electrical properties of plant
      tissue have been used to estimate quality in fruits, and water content in plants,
      as well as nutrient deficiency, which suggests that they have potential for use
      in plant N determination. 

PMID- 23959243
TI  - Principle research on a single mass piezoelectric six-degrees-of-freedom
      accelerometer.
AB  - A signal mass piezoelectric six-degrees-of-freedom (six-DOF) accelerometer is put
      forward in response to the need for health monitoring of the dynamic vibration
      characteristics of high grade digitally controlled machine tools. The operating
      principle of the piezoelectric six-degrees-of-freedom accelerometer is analyzed,
      and its structure model is constructed. The numerical simulation model (finite
      element model) of the six axis accelerometer is established. Piezoelectric quartz
      is chosen for the acceleration sensing element and conversion element, and its
      static sensitivity, static coupling interference and dynamic natural frequency,
      dynamic cross coupling are analyzed by ANSYS software. Research results show that
      the piezoelectric six-DOF accelerometer has advantages of simple and rational
      structure, correct sensing principle and mathematic model, good linearity, high
      rigidity, and theoretical natural frequency is more than 25 kHz, no nonlinear
      cross coupling and no complex decoupling work. 

PMID- 23959244
TI  - Tacholess envelope order analysis and its application to fault detection of
      rolling element bearings with varying speeds.
AB  - Vibration analysis is an effective tool for the condition monitoring and fault
      diagnosis of rolling element bearings. Conventional diagnostic methods are based
      on the stationary assumption, thus they are not applicable to the diagnosis of
      bearings working under varying speed. This constraint limits the bearing
      diagnosis to the industrial application significantly. In order to extend the
      conventional diagnostic methods to speed variation cases, a tacholess envelope
      order analysis technique is proposed in this paper. In the proposed technique, a
      tacholess order tracking (TLOT) method is first introduced to extract the
      tachometer information from the vibration signal itself. On this basis, an
      envelope order spectrum (EOS) is utilized to recover the bearing characteristic
      frequencies in the order domain. By combining the advantages of TLOT and EOS, the
      proposed technique is capable of detecting bearing faults under varying speeds,
      even without the use of a tachometer. The effectiveness of the proposed method is
      demonstrated by both simulated signals and real vibration signals collected from
      locomotive roller bearings with faults on inner race, outer race and rollers,
      respectively. Analyzed results show that the proposed method could identify
      different bearing faults effectively and accurately under speed varying
      conditions. 

PMID- 23959246
TI  - Variables explaining health-related quality of life in community-dwelling older
      adults.
AB  - BACKGROUND AND PURPOSE: Although health-related quality of life (HRQL) has been
      linked to numerous factors in older adults, limited or conflicting studies have
      investigated variables explaining HRQL in healthy, community-dwelling older
      adults. The purpose of this study was to determine whether physical activity,
      gait speed, balance, strength, endurance, and flexibility were associated with
      HRQL in healthy, community-dwelling older adults. METHODS: Participants of this
      cross-sectional, correlational research design study included residents of a
      senior living community, aged 60 years and older who were independent in at least
      unlimited household ambulation. These residents participated in tests of physical
      activity, gait speed, balance, strength, endurance, flexibility, and HRQL
      (Medical Outcomes Study Short-Form Health Survey, SF-36). The physical (PCS) and
      mental (MCS) component summary scores of the SF-36 were calculated. RESULTS: Data
      were collected on 84 participants (mean [SD] age = 78.6 (5.9) years, 54.8%
      women). Significant correlations were found between the PCS and fast gait speed
      (FGS) (r = 0.43; p < .001), the Fullerton Advanced Balance Scale (r = 0.44; p <
      .001), 8-ft up-and-go (r = -0.34; p = .002), and chair stand (r = 0.37; P =
      .001). Only body mass index (BMI) (r = 0.30; p = .007) was significantly
      correlated with MCS. Forward stepwise linear regression analyses were conducted,
      controlling for age, sex, and BMI, to identify factors associated with the PCS
      and MCS. In the model using PCS as the dependent variable, FGS accounted for 26%
      of the variance (R2 change) in PCS over and above age, sex, and BMI (R2 change =
      0.03); for the full model, F = 5.37, p = .001. In the regression analysis using
      MCS as the dependent variable, only the 8-ft up-and-go was retained (R2 change =
      0.06) over and above age, sex, and BMI (R2 change = 0.16); for the full model, F
      = 3.71, p = .01. DISCUSSION: Fast gait speed, balance, and lower body strength
      were associated with the PCS of the SF-36; however, FGS was the only variable
      that uniquely contributed to the variance in the PCS. Body mass index was
      associated with the MCS; however, only balance uniquely contributed to the
      variance in the MCS. Physical activity was not associated with the PCS or MCS.
      CONCLUSIONS: The results of this study support the assessment of FGS in community
      dwelling older adults to gain insight into physical health status. Interventions
      directed toward FGS, balance, and BMI may contribute to optimum HRQL in this
      population.

PMID- 23959245
TI  - Activity-based anorexia has differential effects on apical dendritic branching in
      dorsal and ventral hippocampal CA1.
AB  - Anorexia nervosa (AN) is an eating disorder to which adolescent females are
      particularly vulnerable. Like AN, activity-based anorexia (ABA), a rodent model
      of AN, results in elevation of stress hormones and has genetic links to anxiety
      disorders. The hippocampus plays a key role in the regulation of anxiety and
      responds with structural changes to hormones and stress, suggesting that it may
      play a role in AN. The hippocampus of ABA animals exhibits increased brain
      derived neurotrophic factor and increased GABA receptor expression, but the
      structural effects of ABA have not been studied. We used Golgi staining of
      neurons to determine whether ABA in female rats during adolescence results in
      structural changes to the apical dendrites in hippocampal CA1 and contrasted to
      the effects of food restriction (FR) and exercise (EX), the environmental factors
      used to induce ABA. In the dorsal hippocampus, which preferentially mediates
      spatial learning and cognition, cells of ABA animals had less total dendritic
      length and fewer dendritic branches in stratum radiatum (SR) than in control
      (CON). In the ventral hippocampus, which preferentially mediates anxiety, ABA
      evoked more branching in SR than CON. In both dorsal and ventral regions, the
      main effect of exercise was localized to the SR while the main effect of food
      restriction occurred in the stratum lacunosum-moleculare. Taken together with
      data on spine density, these results indicate that ABA elicits pathway-specific
      changes in the hippocampus that may underlie the increased anxiety and reduced
      behavioral flexibility observed in ABA.

PMID- 23959247
TI  - Jump test performance and sarcopenia status in men and women, 55 to 75 years of
      age.
AB  - BACKGROUND AND PURPOSE: Jumping mechanography uses maximal countermovement jumps
      to test obtain such as jump power (JPow). Recently, it has been shown to be a
      safe method for assessing muscle function in older adults; however, little is
      known about the relationships between JPow, muscle strength, and sarcopenia
      status. The purpose of this study was to examine jump performance, muscle
      strength, and sarcopenia status in older adults. METHODS: This was a cross
      sectional study that included men (n = 27) and women (n = 33) (55-75 years)
      recruited from the general community. Participants completed health status and
      physical activity questionnaires. Body composition, including appendicular
      skeletal muscle mass (ASM), bone free lean body mass, and relative skeletal
      muscle mass index, were assessed by total body dual-energy x-ray absorptiometry
      scans. The criteria for sarcopenia were relative skeletal muscle mass index
      values less than 7.26 kg/m2 for men and less than 5.45 kg/m2 for women. Three
      vertical jumps on a jump mat were performed to assess JPow, jump velocity (JVel),
      and jump height (JHt). Muscle strength was measured by 1RM testing for leg press
      (LP) and right and left hip abduction isotonic resistance exercises. RESULTS:
      Sarcopenia was found in 20% (12/60) of the participants. Jump power was
      significantly lower (P = .001) in the sarcopenia group than in the normal group,
      651.1 (41.7) W versus 851.0 (27.4) W, respectively. Jump power and JHt were
      significantly (P < .01) positively correlated (r = 0.54-0.77) with ASM and bone
      free lean body mass. Significant (P < .01) positive correlations (r = 0.43-0.70)
      were also reported between jump test variables (JPow, JVel, JHt) and muscle
      strength (LP, right and left hip abduction). DISCUSSION: The jump test protocol
      was conducted safely with no injuries or balance issues. Our finding of lower
      JPow in sarcopenic individuals adds new information to the existing literature on
      age-related declines in muscle power. CONCLUSION: Community-dwelling individuals
      classified as sarcopenic had significantly lower JPow but not muscle strength
      compared with their counterparts with normal amounts of muscle mass. Jump test
      variables were positively correlated with lean tissue and lower body muscle
      strength. Based on our findings, JPow may be useful for sarcopenia screening in
      the middle-aged and older adults; however, more research is needed to determine
      the utility of this method in clinical populations.

PMID- 23959248
TI  - Surface modification of electrospun polyester nanofibers with cyclodextrin
      polymer for the removal of phenanthrene from aqueous solution.
AB  - Surface modified electrospun polyester (PET) nanofibers with cyclodextrin polymer
      (CDP) were produced (PET/CDP). CDP formation onto electrospun PET nanofibers was
      achieved by polymerization between citric acid (CTR, crosslinking agent) and
      cyclodextrin (CD). Three different types of native CD (alpha-CD, beta-CD and
      gamma-CD) were used to form CDP. Water-insoluble crosslinked CDP coating was
      permanently adhered onto the PET nanofibers. SEM imaging indicated that the
      nanofibrous structure of PET mats was preserved after CDP surface modification
      process. PET/CDP nanofibers have shown rougher/irregular surface and larger fiber
      diameter when compared to untreated PET nanofibers. The surface analyses of
      PET/CDP nanofibers by XPS elucidated that CDP was present on the fiber surface.
      DMA analyses revealed the enhanced mechanical properties for PET/CDP where
      PET/CDP nanofibers have shown higher storage modulus and higher glass transition
      temperature compared to untreated PET nanofibers. The surface area of the PET/CDP
      nanofibers investigated by BET measurements showed slight decrease due to the
      presence of CDP coating compared to pristine PET nanofibers. Yet, it was observed
      that PET/CDP nanofibers were more efficient for the removal of phenanthrene as a
      model polycyclic aromatic hydrocarbon (PAH) from aqueous solution when compared
      to pristine PET nanofibers. Our findings suggested that PET/CDP nanofibers can be
      a very good candidate as a filter material for water purification and waste
      treatment owing to their very large surface area as well as inclusion
      complexation capability of surface associated CDP. 

PMID- 23959249
TI  - Nanoscale zero-valent iron supported on mesoporous silica: characterization and
      reactivity for Cr(VI) removal from aqueous solution.
AB  - MCM-41-supported nanoscale zero-valent iron (nZVI) was sytnhesized by
      impregnating the mesoporous silica martix with ferric chloride, followed by
      chemical reduction with NaHB4. The samples were studied with a combination of
      characterization techniques such as powder X-ray diffraction (XRD), Fourier
      transform infrared (FT-IR) and Mossbauer spectroscopy, N2 adsorption
      measurements, transmission electron microscopy (TEM), magnetization measurements,
      and thermal analysis methods. The experimental data revealed development of
      nanoscale zero-valent iron particles with an elliptical shape and a maximum size
      of ~80 nm, which were randomly distributed and immobilized on the mesoporous
      silica surface. Surface area measurements showed that the porous MCM-41 host
      matrix maintains its hexagonal mesoporous order structure and exhibits a
      considerable high surface area (609 m(2)/g). Mossbauer and magnetization
      measurements confirmed the presence of core-shell iron nanoparticles composed of
      a ferromagnetic metallic core and an oxide/hydroxide shell. The kinetic studies
      demonstrated a rapid removal of Cr(VI) ions from the aqueous solutions in the
      presence of these stabilized nZVI particles on MCM-41, and a considerably
      increased reduction capacity per unit mass of material in comparison to that of
      unsupported nZVI. The results also indicate a highly pH-dependent reduction
      efficiency of the material, whereas their kinetics was described by a pseudo
      first order kinetic model.

PMID- 23959250
TI  - Treatment of radioactive wastewater using direct contact membrane distillation.
AB  - Direct contact membrane distillation (DCMD) was used to treat low level
      radioactive wastewater (LLRW). The dusty gas model (DGM) was used to analyze the
      mass transfer mechanism and calculate the permeate flux. The operating parameters
      such as feed temperature, feed velocity and feed concentration were studied. The
      experimental results showed that DCMD process can separate almost all Cs(+),
      Sr(2+) and Co(2+) from wastewater. The permeate flux decreased linearly when
      NaNO3 concentration increased from 1.0 to 200 g/L. The permeate flux remained
      about 60% of its initial flux even when NaNO3 concentration in feed solution was
      as high as 200 g/L. The dusty gas model can be successfully applied to estimate
      the mass transfer, and the experimental permeate flux values fitted well with
      that calculated by DGM. DCMD is a promising separation process for low level
      radioactive wastewater treatment.

PMID- 23959251
TI  - Aluminum recovery as a product with high added value using aluminum hazardous
      waste.
AB  - The samples of hazardous aluminum solid waste such as dross were physically and
      chemically characterized. A relationship between density, porosity and metal
      content of dross was established. The paper also examines the chemical reactions
      involving aluminum dross in landfill and the negative consequences. To avoid
      environmental problems and to recovery the aluminum, a processing method was
      developed and aluminum was recovered as an added value product such as alumina.
      This method refers to a process at low temperature, in more stages: acid
      leaching, purification, precipitation and calcination. At the end of this process
      aluminum was extracted, first as Al(3+) soluble ions and final as alumina
      product. The composition of the aluminum dross and alumina powder obtained were
      measured by applying the leaching tests, using atomic absorption spectrometry
      (AAS) and chemical analysis. The mineralogical composition of aluminum dross
      samples and alumina product were determined by X-ray diffraction (XRD) and the
      morphological characterization was performed by scanning electron microscopy
      (SEM). The method presented in this work allows the use of hazardous aluminum
      solid waste as raw material to recover an important fraction from soluble
      aluminum content as an added value product, alumina, with high grade purity
      (99.28%). 

PMID- 23959252
TI  - Characteristics of THMFP increase in secondary effluent and its potential
      toxicity.
AB  - Chlorination of the secondary effluent from domestic wastewater treatment plants
      (WWTP) is suspicious of toxic effects due to the formation of trihalomethanes
      (THMs). In order to clarify this mechanism, samples were collected from the inlet
      and outlet of a WWTP, and a series of analyses were conducted on the relationship
      between THMs formation and the toxicity of the secondary effluent after
      chlorination. By three-dimensional fluorescence spectrometry it was clarified
      that the biological wastewater treatment process was accompanied with the
      formation of humic- and fulvic-like substances which were typical THMs precursors
      as shown by their high thihalomethane formation potential (THMFP) as well as high
      specific ultraviolet absorbance (SUVA). As a result of bioassay using a
      freshwater luminescent bacterium Vibrio-qinghaiensis sp.-Q67, a linear
      relationship was obtained between the concentration of THMs after chlorinating
      the effluent and its toxicity expressed as the inhibition of the luminescent
      light. The effective THMs concentration corresponding to a 50% inhibition was 318
      MUg/L at a chlorine dose of 19.6 mg/L as Cl2. THMs formation may be the direct
      reason for the increase of toxicity in the secondary effluent when chlorine was
      used as disinfectant.

PMID- 23959253
TI  - Copper changes the yield and cadmium/zinc accumulation and cellular distribution
      in the cadmium/zinc hyperaccumulator Sedum plumbizincicola.
AB  - Non-accumulated metals in mixed metal contaminated soils may affect
      hyperaccumulator growth and metal accumulation and thus remediation efficiency.
      Two hydroponics experiments were conducted to investigate the effects of copper
      (Cu) on cadmium (Cd) and zinc (Zn) accumulation by the Cd/Zn hyperaccumulator
      Sedum plumbizincicola, Cu toxicity and plant detoxification using chemical
      sequential extraction of metals, sub-cellular separation, micro synchrotron
      radiation based X-ray fluorescence, and transmission electron microscopy.
      Compared with the control (0.31 MUM Cu), 5-50 MUM Cu had no significant effect on
      Cd/Zn accumulation, but Cu at 200 MUM induced root cell plasmolysis and
      disordered chloroplast structure. The plants held Cu in the roots and cell walls
      and complexed Cu in insoluble forms as their main detoxification mechanisms.
      Exposure to 200 MUM Cu for 4 days inhibited plant Cd uptake and translocation but
      did not affect Zn concentrations in roots and stems. Moreover, unloading of Cd
      and Zn from stem to leaf was restrained compared to control plants, perhaps due
      to Cu accumulation in leaf veins. Copper may thus interfere with root Cd uptake
      and restrain Cd/Zn unloading to the leaves. Further investigation of how Cu
      affects plant metal uptake may help elucidate the Cd/Zn hyper-accumulating
      mechanisms of S. plumbizincicola.

PMID- 23959254
TI  - Graphene-spindle shaped TiO2 mesocrystal composites: facile synthesis and
      enhanced visible light photocatalytic performance.
AB  - Graphene (GR)-TiO2 mesocrystal composites were prepared by a facile template-free
      process based on the combination of sol-gel and solvothermal methods, and were
      characterized using field emission scanning electron microscopy (FE-SEM),
      transmission electron microscopy (TEM), high-resolution transmission electron
      microscopy (HRTEM), X-ray diffraction (XRD), Raman spectroscopy, UV-vis diffuse
      reflectance spectroscopy (UV-vis DRS), nitrogen absorption and electron spin
      resonance (ESR). Visible light photocatalytic performance of GR-TiO2 composites
      was evaluated for photocatalytic degradation of organic dye Rhodamine B. It was
      found that the amount of graphene oxide (GO) added obviously affects morphologies
      of TiO2 mesocrystals and photocatalytic activities of as-prepared nanocomposites.
      Composites prepared in the presence of different amounts of GO all exhibit higher
      photocatalytic activity than pure TiO2 mesocrystals and P25, the composite
      obtained by using 20mg GO presents the most uniform TiO2 mesocrystals in the
      composite and shows the highest photocatalytic efficiency. The mechanism for the
      generation of TiO2 mesocrystals in the GR-TiO2 composite is proposed and possible
      reasons for the enhancement in visible light photocatalytic efficiency are also
      discussed.

PMID- 23959255
TI  - Bioremediation potential of soil contaminated with highly substituted
      polychlorinated dibenzo-p-dioxins and dibenzofurans: microcosm study and
      microbial community analysis.
AB  - Highly chlorinated dibenzo-p-dioxins/dibenzofurans (DD/Fs) are main hazardous
      dioxins, and ubiquitously distributed in the environment. To study the
      feasibility of bioremediation for remedying contamination of highly chlorinated
      dioxins, closed microcosms were constructed with soil from a chronological site
      under oxygen-stimulated conditions. The results showed that high levels of near
      fully and fully chlorinated DD/Fs, particularly octachlorodibenzofuran were
      effectually reduced without accumulation of less substituted congeners. The clone
      library analysis of PCR-amplified 16S rRNA gene from the octachlorodibenzofuran
      degrading consortia showed that 98.3% of the detected sequences were affiliated
      with Proteobacteria. The obtained strains with putative aromatic dioxygenase
      genes and abilities to repetitively grow in octachlorodibenzofuran-containing
      agars were closely related to members within Actinobacteria, Firmicutes, and
      Proteobacteria. Among them, certain Rhodococcus, Micrococcus, Mesorhizobium and
      Bacillus isolates could degrade octachlorodibenzofuran with efficiencies of 26
      43% within 21 days. Hierarchical oligonucleotide primer extension analysis
      further showed that Micrococcus, Rhizobium, Pseudoxanthomonas, and Brevudimonas
      populations increased largely when high concentrations of octachlorodibenzofuran
      were reduced. Overall, our results suggest that a distinctive microbial
      composition and population dynamic could be required for the enhanced degradation
      of highly chlorinated DD/Fs in the batch microcosm and highlight a potential of
      bioremediation technologies in remedying polychlorinated dioxins in the polluted
      sites.

PMID- 23959256
TI  - Removal of hazardous chlorinated VOCs from aqueous solutions using novel ZSM-5
      loaded PDMS/PVDF composite membrane consisting of three hydrophobic layers.
AB  - Hydrophobic polymer possesses significant potential for selective separation of
      volatile organic compounds (VOCs) from their aqueous solutions by pervaporation
      (PV). In the present study mixed matrix hydrophobic membranes of
      polydimethylsiloxane (PDMS) supported on polyvinylidenefluoride (PVDF) substrate
      were synthesized by incorporating hydrophobic inorganic ZSM-5 filler. The
      indigenous membranes were crosslinked with tetraethylorthosilicate (TEOS) for the
      extraction of volatile chlorinated hydrocarbons such as dichloromethane (DCM),
      trichloromethane (TCM), 1,2-dichloroethane (DCE), and 1,1,2,2-tetrachloroethane
      (TeCE), which pose serious environment threat and health hazard. Thermal
      stability, crosslinking, crystallinity, surface morphology and swelling
      characteristics of the indigenously developed membranes were determined by TGA,
      FTIR, XRD, SEM and sorption studies, respectively. Effect of operating parameters
      such as feed composition and filler concentration on separation performance in
      terms of flux and selectivity were determined. Flux of DCM, TCM, DCE and TeCE was
      found to be 0.166, 0.146, 0.141 and 0.06 kg m(-2)h(-1) with selectivity of 541,
      1068, 917 and 15,000, respectively, for 20% ZSM-5 filled PDMS membrane for
      aqueous feeds containing 1.33% (w/v) DCM, 0.8% (w/v) TCM, 0.84% (w/v) DCE and
      0.28% (w/v) TeCE in water. The membrane exhibited considerable feasibility for
      scale-up with significant potential for removal of hazardous chlorinated VOCs
      from aqueous solutions.

PMID- 23959257
TI  - Positive association between urinary levels of 8-hydroxydeoxyguanosine and the
      acrylamide metabolite N-acetyl-S-(propionamide)-cysteine in adolescents and young
      adults.
AB  - Acrylamide is present in mainstream cigarette smoke and in some foods prepared at
      high temperatures. Animal studies have shown that acrylamide exposure increases
      oxidative stress; however, it is not known if this also occurs in humans. We
      recruited 800 subjects (mean age, 21.3 years, range, 12-30 years) from a
      population-based sample of Taiwanese adolescents and young adults to determine if
      urinary levels of the acrylamide metabolite N-acetyl-S-(propionamide)-cysteine
      (AAMA) and the oxidative stress product 8-hydroxydeoxyguanosine (8-OHdG) are
      associated. The mean (SD) AAMA and 8-OHdG were 76.54 (76.42)MUg/L and 3.48
      (2.37)MUg/L, respectively. In linear regression analyses, a 1-unit increase in
      natural log AAMA was significantly associated with an increase in natural log 8
      OHdG (MUg/g creatinine) (beta=0.044, SE=0.019, P=0.020) after controlling for
      covariates. Subpopulation analyses showed AAMA and 8-OHdG were significantly
      associated with males, adolescents, non-current smokers, without alcohol
      consumption, subjects, body mass index >= 24, and homeostasis model assessment of
      insulin resistance score >= 0.9. In conclusion, higher urinary AAMA
      concentrations were associated with increased levels of urinary 8-OHdG in this
      cohort. Further studies are warranted to determine if there is a causal
      relationship between acrylamide exposure and oxidative stress.

PMID- 23959258
TI  - Association of AMD-like retinopathy development with an Alzheimer's disease
      metabolic pathway in OXYS rats.
AB  - The main cause of vision loss in older individuals is age-related macular
      degeneration (AMD)--a complex multifactorial disease, whose etiology and
      pathogenesis are not completely understood. This is due to the impossibility of
      investigating the early stages of AMD and paucity of biological models. The
      senescence-accelerated OXYS rats develop retinopathy with clinical and
      morphological manifestations similar to AMD. But the genetic determinants of its
      development are not known. Previously we identified quantitative trait loci
      (QTLs) associated with the development of cataract, retinopathy, and behavioral
      signs in OXYS rat. In this study, we used bioinformatic analysis to show the
      enrichment of QTL region with genes associated with neurodegeneration, including
      a pathway of Alzheimer's disease. For selected list of candidate genes we
      designed oligonucleotide DNA chips. Using them we found small but significant
      changes in expression of several genes in OXYS retina compared to disease-free
      Wistar rats. Among the genes with altered expression were Picalm and Apba2, known
      to be participants in the processing of the beta-amyloid (Ab). Measurement of Ab
      1-42 in the retina showed that its level increases with age in rats, and at
      advanced stages of retinopathy in OXYS rats, its expression becomes significantly
      higher than that of disease-free Wistar rats. Based on functional annotation of
      QTL, microarray, and ELISA results we suggest that accumulation of Ab may have a
      role in the pathogenesis of retinopathy in OXYS rats.

PMID- 23959259
TI  - Modular synthesis of all-substituted furans through oxidative carbonylation of
      cyclopropenes with tandem metal relay catalysis.
AB  - A modular synthesis of tetrasubstituted furan carboxylates using a tandem
      cycloisomerization/oxidative carbonylation sequence of cyclopropenes has been
      successfully developed. The Tandem Metal Relay Catalysis (TMRC) pathway accounted
      for the high efficiency of this transformation. 

PMID- 23959260
TI  - Molecular cloning, characterization and expression analysis of multiple leptin
      genes in Jian carp (Cyprinus carpio var. Jian).
AB  - Three leptin genes (jlLEP-A1, jlLEP-A2 and jlLEP-B) were cloned and characterized
      in Jian carp (Cyprinus carpio var. Jian), with a highly conserved organization
      encoded by two exons and one intron. jlLEP-A1 and jlLEP-A2 contained 93 and 102bp
      introns, respectively, encoding a 171-amino acid protein. jlLEP-B contained a
      687bp intron encoding a 168-aa protein. jlLEP-A1 and jlLEP-A2 shared 82.5%
      identity, but only 29.2% and 28.6% with jlLEP-B, respectively. jlLEP-A1, jlLEP
      A2, and jlLEP-B were expressed in a wide range of tissues, but the expression
      pattern differed between juveniles and adults (and females and males). In
      juveniles, the expression of jlLEP-A1 and jlLEP-B was higher than jlLEP-A2, and
      was the highest in the liver and gonad. In females, jlLEP-A1 and jlLEP-A2
      expression was the highest in the hypothalamus and liver, whereas jlLEP-B mRNA
      was detected at low levels in all tissues. In males, jlLEP-A1 mRNA was expressed
      primarily in the hypothalamus, with only very low levels in the peripheral
      tissues. jlLEP-A2 and jlLEP-B mRNA were primarily expressed in the muscle,
      hypothalamus, and liver. The expression of jlLEP-A1 and jlLEP-B mRNA was high in
      the ovary and testis, respectively. Our results suggest that leptins play an
      important physiological role in reproduction. 

PMID- 23959261
TI  - The hyper-envelope modeling interface (HEMI): a novel approach illustrated
      through predicting tamarisk (Tamarix spp.) habitat in the Western USA.
AB  - Habitat suitability maps are commonly created by modeling a species'
      environmental niche from occurrences and environmental characteristics. Here, we
      introduce the hyper-envelope modeling interface (HEMI), providing a new method
      for creating habitat suitability models using Bezier surfaces to model a species
      niche in environmental space. HEMI allows modeled surfaces to be visualized and
      edited in environmental space based on expert knowledge and does not require
      absence points for model development. The modeled surfaces require relatively few
      parameters compared to similar modeling approaches and may produce models that
      better match ecological niche theory. As a case study, we modeled the invasive
      species tamarisk (Tamarix spp.) in the western USA. We compare results from HEMI
      with those from existing similar modeling approaches (including BioClim,
      BioMapper, and Maxent). We used synthetic surfaces to create visualizations of
      the various models in environmental space and used modified area under the curve
      (AUC) statistic and akaike information criterion (AIC) as measures of model
      performance. We show that HEMI produced slightly better AUC values, except for
      Maxent and better AIC values overall. HEMI created a model with only ten
      parameters while Maxent produced a model with over 100 and BioClim used only
      eight. Additionally, HEMI allowed visualization and editing of the model in
      environmental space to develop alternative potential habitat scenarios. The use
      of Bezier surfaces can provide simple models that match our expectations of
      biological niche models and, at least in some cases, out-perform more complex
      approaches.

PMID- 23959262
TI  - The dissociation of glycolate-astrochemical and prebiotic relevance.
AB  - On the basis of mass spectrometric experiments and quantum chemical calculations,
      including detailed kinetic and dynamics calculations, we report the unimolecular
      dissociation of an isolated glycolate anion. The dominating processes are: loss
      of formaldehyde; loss of carbon monoxide; loss of carbon dioxide; and loss of a
      hydrogen molecule, with the latter having the lowest energetic threshold. At
      higher energies, CO loss is the dominating reaction. The loss of CO may be
      followed by a second CO loss, leading to the H(-)H2O complex in close mechanistic
      relationship to the Nibbering reaction. The results provide valuable insights
      into possible mechanisms for interstellar and prebiotic formation of glycolate
      via the reverse of the unimolecular dissociation reactions. We propose that the
      addition of the complex of OH(-) and CO to CH2O is the most feasible route to gas
      phase synthesis of glycolate, since all species are abundant in interstellar
      space. 

PMID- 23959263
TI  - SYNE1 mutations in autosomal recessive cerebellar ataxia.
AB  - IMPORTANCE: Autosomal recessive cerebellar ataxia type I, also known as recessive
      ataxia of Beauce, is a slowly progressive ataxia that leads to moderate
      disability with gait ataxia, dysarthria, dysmetria, mild oculomotor
      abnormalities, and diffuse cerebellar atrophy on brain imaging. Mutations in the
      synaptic nuclear envelope protein 1 (SYNE1) gene, located on chromosome 6p25,
      were first reported in patients who originated from a region known as "Beauce" in
      the province of Quebec, Canada. OBJECTIVE: To better evaluate the prevalence of
      SYNE1 mutations in individuals with mild pure cerebellar ataxia and cerebellar
      atrophy, we screened the gene in additional French-Canadian (FC) families and
      individuals from other populations. DESIGN, SETTING, AND PARTICIPANTS: Study
      participants were referred by their treating physician on the basis of core
      features of autosomal recessive cerebellar ataxia type I. After excluding
      individuals with known SYNE1 mutations, our cohort was composed mainly of 19 FCs
      and 21 individuals from other ethnic backgrounds. INTERVENTIONS: Extraction of
      DNA from blood samples and complete resequencing of the SYNE1 gene. MAIN OUTCOMES
      AND MEASURES: The involvement of SYNE1 mutations in individuals with ataxia
      worldwide by resequencing the SYNE1 gene. RESULTS: Two novel truncating mutations
      were found among the FC participants, and 2 other novel mutations were found in a
      patient from France and a patient from Brazil (1 mutation each). CONCLUSIONS AND
      RELEVANCE: This is the second report, to our knowledge, of SYNE1 gene mutations
      in a population other than FCs. These data suggest that mutations in SYNE1 should
      be investigated in families with cerebellar ataxia who live outside the FC
      region.

PMID- 23959264
TI  - Androgen receptor expression: prognostic value in locally advanced squamous cell
      carcinoma of the head and neck.
AB  - BACKGROUND AND PURPOSE: This study investigated the prognostic value of androgen
      receptor (AR) expression of tumor cells in patients treated with surgery and
      subsequent radio(chemo)therapy for locally advanced squamous cell carcinoma of
      the head and neck (SCCHN). MATERIAL AND METHODS: The impact of AR and 11
      additional factors on locoregional control (LRC), metastases-free survival (MFS),
      and overall survival (OS) was retrospectively studied in 163 patients with
      nonmetastatic stage III/IV SCCHN. Additional factors included age, gender, ECOG
      performance status, pre-radiotherapy (pre-RT) hemoglobin levels, tumor site,
      histologic grade, T category, N category, HPV status, extent of resection, and
      concurrent chemotherapy. RESULTS: On multivariate analysis, improved LRC was
      significantly associated with pre-RT hemoglobin levels>=12 g/dl (risk ratio [RR]
      2.22; 95% confidence interval [CI] 1.19-4.13; p=0.013), tumor site (RR 1.39; 95%
      CI 1.14-1.70; p=0.001), lower T category (RR 1.67; 95% CI 1.18-2.44; p=0.003),
      and lower N category (RR 4.18; 95% CI 1.90-10.55; p<0.001). Improved MFS was
      associated with AR expression (RR 2.21; 95% CI 1.01-5.41; p=0.048), better ECOG
      performance status (RR 3.19; 95% CI 1.50-7.14; p=0.003), lower T category (RR
      2.24; 95% CI 1.47-3.65; p<0.001), and lower N category (RR 5.33; 95% CI 2.07
      16.63; p<0.001). OS was positively associated with AR expression (RR 1.99; 95% CI
      1.06-4.00; p=0.032), better ECOG performance status (RR 2.20; 95% CI 1.20-4.09;
      p=0.010), pre-RT hemoglobin levels>=12 g/dl (RR 2.13; 95% CI 1.19-3.82; p=0.012),
      lower T category (RR 1.81; 95% CI 1.30-2.62; p<0.001), and lower N category (RR
      3.41; 95% CI: 1.65-7.80; p<0.001). CONCLUSION: Tumor cell expression of AR was an
      independent prognostic factor for MFS and OS and should be considered in future
      prospective trials.

PMID- 23959265
TI  - Cinchona-based squaramide-catalysed cascade aza-Michael-Michael addition:
      enantioselective construction of functionalized spirooxindole
      tetrahydroquinolines.
AB  - An efficient enantioselective cascade aza-Michael-Michael addition reaction
      catalysed by a chiral bifunctional tertiary amine-squaramide catalyst has been
      developed. This cascade reaction proceeded well under mild conditions, furnishing
      highly functionalized spirooxindole tetrahydroquinolines with three contiguous
      stereocenters in excellent yields with excellent diastereoselectivities (>25:1
      dr) and high enantioselectivities (up to 94% ee).

PMID- 23959267
TI  - Targeted therapies: Hope for antiangiogenic therapy in advanced gastric cancer.

PMID- 23959268
TI  - Genetics: Glioblastoma landscape revealed.

PMID- 23959266
TI  - ZRX1, the first EGFR inhibitor-capecitabine based combi-molecule, requires
      carboxylesterase-mediated hydrolysis for optimal activity.
AB  - Capecitabine, an orally available prodrug of 5-FU, requires activation by
      carboxylesterase (CES) enzymes present in the liver to generate 5'-deoxy-5
      flurocytidine ribose (5'-DFCR). The deamination of the latter by cytidine
      deaminase gives 5'-deoxy-5-fluorouridine ribose (5'-DFUR). Finally, the
      conversion of 5'-DFUR to the cytotoxic drug 5-FU, occurs primarily in the tumour
      and is catalyzed by thymidine phosphorylase (TP). Accordingly, it was surmised
      that events associated with an increase of TP levels should enhance the potency
      of capecitabine and its metabolites. EGFR inhibition was found to be one such
      event. The observed synergy between gefitinib and 5'-DFUR has inspired the design
      of single molecules capable of acting as prodrugs of both an EGFR inhibitor and 5
      FU. Here, we report on the synthesis and characterization of one such molecule,
      ZRX1, that consists of an acetylated 5'-DFCR moiety linked to a quinazoline
      inhibitor of EGFR through an alkyl dicarbamate spacer that requires CES
      activation to generate the two active metabolites. Our results showed that ZRX1
      was ineffective as an intact molecule. However, when CES was present, ZRX1
      induced an increase in EGFR inhibition, TP expression, DNA damage and apoptosis.
      ZRX1 was, at least, 3-fold more potent than capecitabine and 5'-DFUR and
      recapitulated the effects of the combination treatments. LC-MS analysis showed
      that in the presence of CES, ZRX1 is metabolized into a mixture of bioactive
      quinazoline derivatives and 5'-DFCR derived metabolites. Our results in toto,
      suggest that capecitabine-based EGFR targeting combi-molecules of the same type
      than ZRX1, have the potential to induce stronger growth inhibitory potency than
      capecitabine, 5'-DFUR or single EGFR inhibitors and equivalent potency when
      compared with combinations of EGFR inhibitors + 5'-DFUR.

PMID- 23959269
TI  - Targeted therapies: Afatinib--new therapy option for EGFR-mutant lung cancer.

PMID- 23959270
TI  - Lung cancer: Maintenance therapy and precision medicine in NSCLC.

PMID- 23959271
TI  - Commentary on strengthening the assessment of factorial invariance across
      population subgroups: a commentary on Varni et al. (2013).
AB  - In his commentary on Varni et al.'s (Qual Life Res. doi: 10.1007/s11136-013-0370
      4 , 2013) article, McIntosh (Qual Life Res. doi: 10.1007/s11136-013-0465-y ,
      2013) has two main arguments. First, we should have paid more attention to
      statistical tests (i.e., chi 2 values) instead of approximate fit indexes for our
      analysis, especially with the baseline model. Second, Bayesian methods are better
      than the frequentist methods we used in determining the model's invariance across
      age and gender groups. We believe that statistical tests do have a place in
      assessing model fit, but overemphasis on them, especially with larger sample
      sizes, can lead to errant decisions. Second, while we agree that Bayesian methods
      have the potential to contribute much to the field of assessing invariance, more
      development needs to be conducted before they can be widely utilized in assessing
      factorial invariance across groups.

PMID- 23959272
TI  - Binding of V(IV)O2+ to the Fe binding sites of human serum transferrin. A
      theoretical study.
AB  - The binding of V(IV)O2+ to human serum transferrin (hTF) at the FeIII binding
      sites is addressed. Geometry optimization calculations were performed for the
      binding of V(IV)O2+ to the N-terminal lobe of hTF (hTFN), and indicate that in
      the presence of CO32- or HCO3 -, V(IV) is bound to five atoms in a distorted
      geometry. The structures of V(IV)O-hTFN species optimized at the semiempirical
      level were also used to calculate the 51V and 14N A tensors by density functional
      theory methods, and were compared with the reported experimental values.
      Globally, of all the calculated V(IV)O-hTF structures, the one that yields the
      lowest calculated heats of formation and minimum deviations from the experimental
      values of the 51V and 14N A tensor components is the structure that includes CO32
      as a synergistic anion. In this structure the V=O bond length is approximately
      1.6 A, and the vanadium atom is also coordinated to the phenolate oxygen atom of
      Tyr188 (at approximately 1.9 A), the aspartate oxygen atom of Asp63 (at
      approximately 1.9 A), the His249 Ntau atom (at approximately 2.1 A), and a
      carbonate oxygen atom (at approximately 1.8 A). The Tyr95 phenolic ocygen atom is
      approximately 3.3 A from the metal center, and thus is very weakly bound to
      V(IV). All of these oxygen atoms are able to establish dipolar interactions with
      groups of the protein.

PMID- 23959273
TI  - Intergenic polymorphisms in the amphiregulin gene region as biomarkers in
      metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan.
AB  - In the epidermal growth factor receptor (EGFR) pathway, polymorphisms in EGFR and
      its ligand EGF have been studied as biomarkers for anti-EGFR treatment. However,
      the potential pharmacogenetic role of other EGFR ligands such as amphiregulin
      (AREG) and epiregulin (EREG) has not been elucidated. We studied 74 KRAS and BRAF
      wild-type metastatic colorectal cancer patients treated with anti-EGFR plus
      irinotecan. Twenty-two genetic variants in EGFR, EGF, AREG and EREG genes were
      selected using HapMap database and literature resources. Three tagging single
      nucleotide polymorphisms in the AREG gene region (rs11942466 C>A, rs13104811 A>G,
      and rs9996584 C>T) predicted disease control in the multivariate analyses. AREG
      rs11942466 C>A and rs9996584 C>T were also associated with overall survival (OS).
      The functional polymorphism, EGFR rs712829 G>T, was associated with progression
      free and OS. Our findings support that intergenic polymorphisms in the AREG gene
      region might help to identify colorectal cancer patients that will benefit from
      irinotecan plus anti-EGFR therapy. 

PMID- 23959274
TI  - Interethnic differences in the relevance of CYP2C9 genotype and environmental
      factors for diclofenac metabolism in Hispanics from Cuba and Spain.
AB  - The aims of this study were to evaluate the diclofenac metabolism in Hispanics
      from Cuba and Spain and its relation to ethnicity, CYP2C9 genotypes and
      environmental factors. Diclofenac hydroxylation capacity (concentration ratios of
      diclofenac/metabolites in 8-h urine) was studied in 160 Cuban (classified as 76
      Cuban-Whites-CWs and 84 Cuban-Mestizos-CMs) and 148 Spaniard (SPs) healthy
      volunteers. Diclofenac and its main metabolites, 4'-hydroxy (OH), 3'-OH and 5-OH
      diclofenac, and CYP2C9*2 to *6 and *8 alleles were also determined in 132 and 128
      CWs and CMs, respectively. Gender, tobacco, caffeine and ethanol consumption were
      also evaluated. The mean diclofenac/4'-OH diclofenac ratio was higher in CMs
      (0.72+/-0.25) than in CWs (0.64+/-0.20; P<0.05) and SPs (0.57+/-0.26; P<0.001).
      The mean diclofenac/4'-OH diclofenac ratio was higher (P<0.05) in subjects with
      CYP2C9*1/*3 (0.77+/-0.19; n=22) and CYP2C9*1/*8 (0.93+/-0.33; n=4) genotypes than
      with CYP2C9*1/*1 (0.65+/-0.24; n=90). Environmental factors did not seem to
      influence the diclofenac metabolism in these populations. The present findings
      show for the first time interethnic differences between Hispanic groups in
      urinary diclofenac/4'-OH diclofenac ratios, and the relevance of CYP2C9*3 and
      CYP2C9*8 alleles. 

PMID- 23959275
TI  - Aromaticity as the driving force for the stability of non-IPR endohedral
      metallofullerene Bingel-Hirsch adducts.
AB  - We have studied the relative stabilities of Bingel-Hirsch non-IPR endohedral
      metallofullerene monoadducts having one, two, or three adjacent pentagon pairs.
      The most stable addition always leads to an open adduct and never occurs on [5,5]
      bonds. Our results show that the thermodynamics of the addition is governed by
      the additive local aromaticity of the rings of the final adducts. 

PMID- 23959276
TI  - Canadian doctor is new president of MSF International. Interview by Lauren Vogel.

PMID- 23959279
TI  - Hepatitis B virus screening and vaccination in a family from Nigeria.

PMID- 23959280
TI  - The expanding scope of pharmacists' practice: implications for physicians.

PMID- 23959281
TI  - Health Canada should license companies that mix drugs, says report.

PMID- 23959283
TI  - Salon. Cracks in the curriculum: an appreciation.

PMID- 23959284
TI  - Impact of physician continuity on death or urgent readmission after discharge
      among patients with heart failure.
AB  - BACKGROUND: Early physician follow-up after discharge is associated with lower
      rates of death and readmission among patients with heart failure. We explored
      whether physician continuity further influences outcomes after discharge.
      METHODS: We used data from linked administrative databases for all adults aged 20
      years or more in the province of Alberta who were discharged alive from hospital
      between January 1999 and June 2009 with a first-time diagnosis of heart failure.
      We used Cox proportional hazard models with time-dependent covariates to analyze
      the effect of follow-up with a familiar physician within the first month after
      discharge on the primary outcome of death or urgent all-cause readmission over 6
      months. A familiar physician was defined as one who had seen the patient at least
      twice in the year before the index admission or once during the index admission.
      RESULTS: In the first month after discharge, 5336 (21.9%) of the 24 373
      identified patients had no follow-up visits, 16 855 (69.2%) saw a familiar
      physician, and 2182 (9.0%) saw unfamiliar physician(s) exclusively. The risk of
      death or unplanned readmission during the 6-month observation period was lower
      among patients who saw a familiar physician (43.6%; adjusted hazard ratio [HR]
      0.87, 95% confidence interval [CI] 0.83-0.91) or an unfamiliar physician (43.6%;
      adjusted HR 0.90, 95% CI 0.83-0.97) for early follow-up visits, as compared with
      patients who had no follow-up visits (62.9%). Taking into account all follow-up
      visits over the 6-month period, we found that the risk of death or urgent
      readmission was lower among patients who had all of their visits with a familiar
      physician than among those followed by unfamiliar physicians (adjusted HR 0.91,
      95% CI 0.85-0.98). INTERPRETATION: Early physician follow-up after discharge and
      physician continuity were both associated with better outcomes among patients
      with heart failure. Research is needed to explore whether physician continuity is
      important for other conditions and in settings other than recent hospital
      discharge.

PMID- 23959285
TI  - Wolff-Parkinson-White syndrome "cured" by myocardial infarction?

PMID- 23959286
TI  - New CEO transforming The Cochrane Collaboration.

PMID- 23959287
TI  - Fingerprinting used to combat drug-resistant TB in India, Cambodia.

PMID- 23959288
TI  - Gluten-free industry is healthy, but is the food?

PMID- 23959291
TI  - Indian MPs criticise care in medical clinics for government employees.

PMID- 23959290
TI  - Metabolomic identification of diagnostic plasma biomarkers in humans with chronic
      heart failure.
AB  - Chronic heart failure (CHF), as a progressive clinical syndrome, is characterized
      by failure of enough blood supply from the heart to meet the body's metabolic
      demands, and there is intense interest in identifying novel biomarkers that could
      make contributions to the diagnosis of CHF. Metabolomics, compared with current
      diagnostic approaches, could investigate many metabolic perturbations within
      biological systems. The overarching goal of the work discussed here is to apply a
      high-throughput approach to identify metabolic signatures and plasma diagnostic
      biomarkers underlying CHF by 1H-NMR spectroscopy. Plasma samples from 39 patients
      with CHF and 15 controls were analyzed by NMR spectroscopy. After processing the
      data, orthogonal partial least square discriminant analysis (OPLS-DA) was
      performed. The statistical model revealed good explained variance and
      predictability, and the diagnostic performance assessed by leave-one-out analysis
      exhibited 92.31% sensitivity and 86.67% specificity. The OPLS-DA score plots of
      spectra revealed good separation between case and control on the level of
      metabolites, and multiple biochemical changes indicated hyperlipidemia,
      alteration of energy metabolism and other potential biological mechanisms
      underlying CHF. It was concluded that the NMR-based metabolomics approach
      demonstrated good performance to identify diagnostic plasma markers and provided
      new insights into metabolic process related to CHF.

PMID- 23959292
TI  - FDA must publish data on safety and efficacy of prophylactic AIDS drug, court
      rules.

PMID- 23959293
TI  - Roche's decision to drop Herceptin patent in India opens way for generics.

PMID- 23959294
TI  - Uninsured immigrants will continue to put pressure on safety net hospitals in the
      US, says report.

PMID- 23959295
TI  - Cervicoisthmic pregnancy near cesarean scar after oocyte donation in premature
      ovarian failure: literature review starting from a single case.
AB  - OBJECTIVE: This study aimed to identify the best management options in decision
      making in cases of cervicoisthmic and cesarean scar pregnancies and rare forms of
      ectopic pregnancies with high rates of pregnancy-related morbidity in the first
      trimester, more commonly associated with assisted reproductive medicine.
      MATERIALS AND METHODS: We performed a literature review of the description of a
      case report of a cervicoisthmic pregnancy near a cesarean scar in a premature
      ovarian failure woman. She obtained pregnancy after ovum donation, hormonal
      therapy, and in vitro fertilization. The researchers focused on the
      MEDLINE/PubMed database articles on ectopic pregnancies, particularly on cesarean
      scar pregnancies, cervical pregnancies, and ectopic pregnancies after in vitro
      fertilization in English-language journals published from January 1996 to
      December 2011. RESULTS: The conservative or nonconservative options for medical
      or surgical treatments are disposables. Moreover, in literature, no consensus was
      found about the best treatment method. CONCLUSIONS: Obstetricians should pay
      great attention to a possible cesarean scar pregnancy in patients with risk
      factors in their medical history. Until now, the rarity of these findings does
      not allow the definition of a commonly accepted management, so the best
      personalized approach may be guided by early recognition, close surveillance, and
      appropriate counseling. Further investigations are necessary to recognize high
      risk factors for all ectopic pregnancies and those unique to cesarean scar
      ectopic pregnancies.

PMID- 23959296
TI  - Use of electronic health record-based tools to improve appropriate use of the
      human papillomavirus test in adult women.
AB  - OBJECTIVE: To determine whether compliance with guidelines for cervical cancer
      screening, particularly use of the human papillomavirus (HPV) test in adult (aged
      >=21 y) women, improves with the implementation of educational prompts in the
      electronic health record (EHR). MATERIALS AND METHODS: Two EHR-based
      interventions aimed at reducing unindicated HPV tests were implemented in the EHR
      in late June 2010. The Pap order form was revised with a descriptor next to the
      cotest (Pap plus HPV test) option advising that this is not for screening in
      women younger than 30 years, and a link to the American Society for Colposcopy
      and Cervical Pathology Web site was made available on the EHR home page. Charts
      of adult women with HPV results from January to December 2010 were reviewed.
      Appropriateness of HPV test ordering before (period A: from January to June) and
      after (period B: from July to December) the interventions were compared using the
      chi(2) test of association. RESULTS: A total of 3,564 HPV tests were performed on
      adult women at Loyola University Medical Center in 2010. During period A, 1,709
      tests were ordered compared with 1,855 tests ordered during period B (p = .014).
      The proportion of HPV tests without an appropriate indication decreased
      significantly after the EHR changes (20% for period A vs 13% for period B, p <
      .0005). This significant decrease was seen in both primary care (22% in period A
      vs 12% in period B, p < .0005) and obstetrics and gynecology (Ob/Gyn) (19% vs
      13%, p < .0005). CONCLUSIONS: Electronic health record-based tools improve
      compliance with cervical cancer screening guidelines.

PMID- 23959297
TI  - Outcomes after management of young women with cervical intraepithelial neoplasia
      2 with a 6-month observation protocol.
AB  - OBJECTIVE: Recommendations regarding treatment of cervical intraepithelial
      neoplasia (CIN) 2 in women have evolved over the years: young women with CIN 2
      may be offered observation with Pap smears and colposcopy every 6 months instead
      of immediate excision or ablation of disease. The purpose of this study was to
      observe patient follow-up during the initiation of this management protocol for
      young women with CIN 2. MATERIALS AND METHODS: This was a retrospective review of
      clinical outcomes of women younger than 30 years with CIN 2 on index biopsy and
      planned follow-up at UNC between July 2009 and August 2010. A chart review for
      clinical variables, follow-up visits, and progression of disease was conducted.
      Primary analysis determined the rate of follow-up and pathology at 6 months.
      Secondary analysis investigated risk factors for incomplete follow-up. RESULTS:
      Seventy women met inclusion criteria; 46 were managed with observation. Twenty
      eight (60.8%; 28/46) women completed a follow-up visit. Demographic and clinical
      variables did not reach statistical significance in predicting the likelihood of
      completion of a follow-up visit, although there was a trend toward greater follow
      up in employed patients (odds ratio = 5.25, 95% confidence interval = 0.84
      34.78). Approximately half (52.4%; 11/21) of women with a completed cervical
      biopsy demonstrated regression of disease during the study period. CONCLUSIONS:
      On the basis of these data, follow-up in this population was unpredictable based
      on basic demographic or clinical factors that we often use to judge likelihood of
      compliance with medical recommendations. The percentage of patients with
      regression at follow-up was as expected from the natural history of CIN 2.

PMID- 23959298
TI  - Tissue genotyping of 37 in situ and invasive cervical cancer with a concomitant
      negative HC2 HPV DNA test.
AB  - OBJECTIVE: The rare occurrence of histology-proven cervical intraepithelial
      neoplasia grade 3 (CIN 3) or invasive cancer with a negative HC2 result is known.
      Tissue blocks of 37 cases of histology-diagnosed CIN 3+ with a concomitant
      negative HC2 test were genotyped to investigate the human papillomavirus (HPV)
      status within the lesion. METHODS: We considered 1,976 cervical excision
      specimens performed with concomitant HC2 test. Of these, 37 histology-confirmed
      CIN 3+ resulted HC2 negative. Thirty-three paraffin blocks, derived by the
      cervical excision, could be genotyped for high- (HR) and low-risk (LR) HPV
      genotypes. RESULTS: Detailed histology showed 30 CIN 3, 2 squamous cell invasive
      carcinomas, and 5 invasive adenocarcinomas. One specimen resulted not amplifiable
      at the genotyping. Twenty-two cases (68.7%) were positive for HR-HPV types,
      either in single (n = 17) or multiple HR-HPV infection (n = 5). Most of the HR
      HPVs found were 16 or 18. Ten cases (31.3%) were negative for HR-HPV types; 5 of
      these were positive for probable HR-HPV types, not detectable with HC2 HR-probes,
      1 was positive to LR-HPV types, while 1 had HPV-69/71. Three cases were negative
      for HPV DNA, either high or low risk. CONCLUSIONS: Of the rare cases of CIN 3+
      lesions with concomitant negative HC2 test, 69% are true failures in HR-HPV
      detection. One third of HC2-negative CIN 3+ is related to the presence of other
      HPV genotypes not covered by the HC2 panel or to undetectable HPV in the lesion;
      both these rare occurrences were already described in large cancer series and
      partially explain the occurrence of HPV-negative CIN 3+.

PMID- 23959299
TI  - A postconization hematometra revealed a rare case of endocervical bone
      metaplasia.
AB  - BACKGROUND: Hematometra is an unusual occurrence in young women undergoing
      conization; moreover, osseous metaplasia of the uterine cervix is a very rare
      event, with 7 cases in the literature. A postconization hematometra due to
      endocervical ossification is a unique occurrence. The authors report such an
      event. CASE: A young woman undergoing conization developed progressive
      hypoamenorrhea with pelvic pain. Pregnancy test was negative and a transvaginal
      ultrasound showed an image of suspected hematometra. Diagnostic hysteroscopy
      showed an endocervical obstruction due to a bone formation of the uterine cervix,
      which was removed with an office operative hysteroscopy. After surgery, the
      patient restored normal menstrual cycle. Histological examination revealed a
      cervical bone metaplasia. CONCLUSIONS: In premenopausal women undergoing
      conization, the appearance of a progressive hypoamenorrhea with pelvic pain could
      suggest a cervical mechanical obstruction that could be an uncommon stenosis.
      Despite this case represents a very rare event, a postconization hematometra due
      to an endocervical ossification can be managed with an office operative
      hysteroscopy.

PMID- 23959300
TI  - Abnormal pap tests and human papillomavirus infections among HIV-infected and
      uninfected women who have sex with women.
AB  - OBJECTIVE: To estimate the frequency of abnormal Pap and human papillomavirus
      (HPV) positivity among human immunodeficiency virus (HIV)-seropositive and 
      seronegative women who have sex with women (WSW). METHODS: Pap and HPV DNA
      polymerase chain reaction tests were obtained every 6 months from women in a US
      cohort of HIV-seropositive and -seronegative women. Women who have sex with women
      were women reporting no male and at least 1 female sex partner for 5 years. They
      were frequency matched 1:5 to women reporting sex only with men (WSM) and
      assessed using multivariable generalized estimating equation logistic regression
      models. RESULTS: Paps at study entry were abnormal in 12 (21%) of 49 HIV
      seropositive WSW, 151 (64%) of 245 HIV-seropositive WSM, 3 (9%) of 24 HIV
      seronegative WSW, and 16 (11%) of 120 HIV-seronegative WSM. Human papillomavirus
      was found at entry in 18 (42%) HIV-seropositive WSW, 109 (52%) HIV-seropositive
      WSM, 6 (27%) HIV-seronegative WSW, and 13 (13%) HIV-seronegative WSM. After
      controlling for HIV serostatus and CD4 count, WSW had marginally lower odds than
      WSM of Pap abnormality (odds ratio = 0.59, 95% confidence interval = 0.33-1.03)
      and of HPV (odds ratio = 0.53, 95% confidence interval = 0.32-0.89). After
      controlling for partner's gender, HIV seropositivity and lower CD4 count were
      associated with any HPV, oncogenic HPV, any abnormal Pap result, and high-grade
      squamous intraepithelial lesion or worse (p < .0001 for all). CONCLUSIONS:
      Although risks for abnormal Pap and HPV are modestly lower in WSW than in WSM,
      both are common in HIV-seropositive women regardless of sexual preference. Both
      WSW and WSM should be screened similarly.

PMID- 23959301
TI  - Kyphoplasty for the treatment of pain distant to osteoporotic thoracolumbar
      compressive fractures.
AB  - Vertebral fractures are one of the most common osteoporotic fractures. We sought
      to investigate the incidence of distant pain after osteoporotic vertebral
      compressive fracture (OVCF) at the thoracolumbar junction, and to explore the
      effect of kyphoplasty in the treatment of distant pain post-OVCF. Eighty-seven
      patients diagnosed OVCF between T11 and L2 were included in the study. The region
      of pain and its proximity to the thoracolumbar compressive fracture was recorded.
      For pain management, all patients received kyphoplasty. The follow-up period was
      every 3 months for 1-year post-surgery. The Visual Analogue Scale (VAS) and
      Oswestry Disability Index (ODI) were used pre-operatively, post-operatively, and
      at 3-, 6-, and 12-month follow-ups to assess patient status. All patients
      completed the operation, with 72 patients having focal pain over the compression
      fracture. Eleven cases also had pain distal to the fracture region in the
      following areas: lower back, near the iliac crest (n = 6), the groin (n = 3), and
      the trochanteric region (n = 2). Four cases had pain in distant to the fracture:
      lower back, near iliac crest (n = 3), and the trochanteric region (n = 1). All
      patients had a significant improvement in clinical symptoms. The average VAS and
      the ODI decreased significantly pre-operatively to post-operatively (p < 0.05).
      In addition to focal tenderness, many patients with thoracolumbar compression
      fractures may have pain distant to the fracture. This can be successfully treated
      using kyphoplasty. This phenomenon also indicates that patients at risk of
      osteoporosis who also have lower back pain should not neglect the potential for a
      thoracolumbar fracture.

PMID- 23959302
TI  - Levels of BNP and stress blood glucose in acute coronary syndrome patients and
      their relationships with the severity of coronary artery lesion.
AB  - This study aims to analyze the clinical significance of the measuring B-type
      natriuretic peptide (BNP) and stress glycemia in patients with acute coronary
      syndrome (ACS), and to investigate the relationships between the two biomarkers
      and the severity of coronary artery lesions. One hundred and five consecutive
      patients with ACS admitted for coronary artery angiography were divided into
      three clinical subgroups. These patients were then further assigned into either
      of three subgroups according to their Gensini score. Moreover, a group of
      patients with stable angina (SA) and those with no history of coronary disease
      served as controls. The patients' BNP levels were analyzed on admission and their
      fasting blood glucose was measured the next morning. BNP and fasting blood
      glucose concentrations were highly elevated in patients with ACS irrespective of
      their subgroups compared to SA and control patients. This observation was
      statistically significant (P < 0.001). Further, the concentrations of BNP and
      fasting blood glucose between the three ACS subgroups were significantly
      different (P < 0.001) depending on the severity of the coronary artery disease.
      There is a positive correlation between levels of BNP and blood glucose
      concentration and Gensini score in ACS patients (r = 0.782, P < 0.05, r = 0.732,
      P < 0.05). BNP level and stress glycemia were significantly higher in ACS
      patients than those in SA and control groups. There is a correlation between BNP
      level and stress blood glucose concentration and the severity of coronary artery
      lesions. Combined analysis of BNP and stress blood glucose can be helpful and
      effective for risk stratification of patients with ACS after admission.

PMID- 23959303
TI  - Pharmacokinetics, Trypanosoma brucei gambiense efficacy, and time of drug action
      of DB829, a preclinical candidate for treatment of second-stage human African
      trypanosomiasis.
AB  - Human African trypanosomiasis (HAT, also called sleeping sickness), a neglected
      tropical disease endemic to sub-Saharan Africa, is caused by the parasites
      Trypanosoma brucei gambiense and T. brucei rhodesiense. Current drugs against
      this disease have significant limitations, including toxicity, increasing
      resistance, and/or a complicated parenteral treatment regimen. DB829 is a novel
      aza-diamidine that demonstrated excellent efficacy in mice infected with T. b.
      rhodesiense or T. b. brucei parasites. The current study examined the
      pharmacokinetics, in vitro and in vivo activity against T. b. gambiense, and time
      of drug action of DB829 in comparison to pentamidine. DB829 showed outstanding in
      vivo efficacy in mice infected with parasites of T. b. gambiense strains, despite
      having higher in vitro 50% inhibitory concentrations (IC50s) than against T. b.
      rhodesiense strain STIB900. A single dose of DB829 administered intraperitoneally
      (5 mg/kg of body weight) cured all mice infected with different T. b. gambiense
      strains. No cross-resistance was observed between DB829 and pentamidine in T. b.
      gambiense strains isolated from melarsoprol-refractory patients. Compared to
      pentamidine, DB829 showed a greater systemic exposure when administered
      intraperitoneally, partially contributing to its improved efficacy. Isothermal
      microcalorimetry and in vivo time-to-kill studies revealed that DB829 is a slower
      acting trypanocidal compound than pentamidine. A single dose of DB829 (20 mg/kg)
      administered intraperitoneally clears parasites from mouse blood within 2 to 5
      days. In summary, DB829 is a promising preclinical candidate for the treatment of
      first- and second-stage HAT caused by both Trypanosoma brucei subspecies. 

PMID- 23959304
TI  - In vitro and in vivo activities of AIC292, a novel HIV-1 nonnucleoside reverse
      transcriptase inhibitor.
AB  - Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are important and
      frequently used elements of highly active antiretroviral therapy (HAART) for the
      treatment of human immunodeficiency virus type 1 (HIV-1) infection. However, the
      development of drug resistance, as well as the side effects of existing drugs,
      defines a medical need for novel NNRTIs with excellent tolerability, improved
      activity against NNRTI-resistant viruses, and a low barrier to resistance. Within
      the chemical class of diarylpyrazole-[imidazolidinone]-carboxamides, AIC292 was
      identified as a promising novel HIV-1 NNRTI and has successfully completed single
      dose clinical phase I studies. Here, we report on the antiviral activity of
      AIC292, evaluated in vitro against wild-type and NNRTI-resistant HIV-1 isolates
      and in vivo using an engineered mouse xenograft model. AIC292 inhibited wild-type
      HIV-1 laboratory strains at low nanomolar concentrations, was well tolerated in
      different cell lines, and showed excellent selectivity in a lead profiling
      screen. In addition, activity of AIC292 could be demonstrated against a broad
      panel of wild-type HIV-1 group M and group O clinical isolates. AIC292 also
      retained activity against viruses harboring NNRTI resistance-associated mutations
      (RAMs), including the most prevalent variants, K103N, Y181C, and G190A.
      Interestingly, viruses bearing the L100I RAM were hypersusceptible to AIC292. Two
      drug combination assays showed no antagonistic interactions between AIC292 and
      representative marketed HIV drugs with regard to antiviral activity. Furthermore,
      AIC292 displayed potent antiviral in vivo efficacy in a mouse xenograft model
      when applied once daily. Taken together, these data show that AIC292 represents a
      molecule with the antiviral properties of a novel NNRTI for the treatment of HIV
      1 infection. 

PMID- 23959306
TI  - Regional resistance surveillance program results for 12 Asia-Pacific nations
      (2011).
AB  - The Regional Resistance Surveillance program monitored susceptibility rates and
      developing resistance by geographic region, including 12 Asia-Pacific (APAC)
      countries. Reference broth microdilution methods for
      susceptibility/interpretations were applied, processing 5,053 strains. Among
      Staphylococcus aureus isolates (37% methicillin-resistant S. aureus [MRSA],
      highest in South Korea [73%]), linezolid (LZD), tigecycline (TIG), and vancomycin
      were 100% active, but 33 and 34% of strains were levofloxacin (LEV) or macrolide
      resistant, respectively. Streptococcus pneumoniae was most resistant to beta
      lactams and macrolides (45%) but was LZD, LEV, and TIG susceptible (>98%).
      Extended-spectrum beta-lactamase (ESBL) phenotype rates in Escherichia coli and
      Klebsiella spp. were 48 and 47%, respectively, and were highest in Taiwan, at 75
      to 91%. The best anti-ESBL-phenotype agents were amikacin (81 to 96%
      susceptible), colistin (COL; >98%), TIG (>98%), and carbapenems (81 to 97%).
      Pseudomonas aeruginosa showed >=20% resistance to all drugs except COL (99%
      susceptible). In conclusion, endemic evolving antimicrobial resistances in APAC
      nations show compromised roles for many commonly used antimicrobials. 

PMID- 23959305
TI  - Preclinical characterization of GLS4, an inhibitor of hepatitis B virus core
      particle assembly.
AB  - Hepatitis B virus (HBV)-associated chronic liver diseases are treated with
      nucleoside analogs that target the virus polymerase. While these analogs are
      potent, drugs are needed to target other virus-encoded gene products to better
      block the virus replication cycle and chronic liver disease. This work further
      characterized GLS4 and compared it to the related BAY 41-4109, both of which
      trigger aberrant HBV core particle assembly, where the virus replication cycle
      occurs. This was done in HepAD38 cells, which replicate HBV to high levels. In
      vitro, GLS4 was significantly less toxic for primary human hepatocytes (P < 0.01
      up to 100 MUM), inhibited virus accumulation in the supernantant of HepAD38 cells
      (P < 0.02 up to 100 nM), inhibited HBV replicative forms in the liver with a
      significantly lower 50% effective concentration (EC50) (P < 0.02), and more
      strongly inhibited core gene expression (P < 0.001 at 100 to 200 nM) compared to
      BAY 41-4109. In vivo characterization was performed in nude mice inoculated with
      HepAD38 cells, which grew out as tumors, resulting in viremia. Treatment of mice
      with GLS4 and BAY 41-4109 showed strong and sustained suppression of virus DNA to
      about the same extents both during and after treatment. Both drugs reduced the
      levels of intracellular core antigen in the tumors. Alanine aminotransferase
      levels were normal. Tumor and total body weights were not affected by treatment.
      Thus, GLS4 was as potent as the prototype, BAY 41-4109, and was superior to
      lamivudine, in that there was little virus relapse after the end of treatment and
      no indication of toxicity. 

PMID- 23959307
TI  - CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of
      albendazole and fenbendazole in human liver microsomes and recombinant P450 assay
      systems.
AB  - Albendazole and fenbendazole are broad-spectrum anthelmintics that undergo
      extensive metabolism to form hydroxyl and sulfoxide metabolites. Although CYP3A
      and flavin-containing monooxygenase have been implicated in sulfoxide metabolite
      formation, the enzymes responsible for hydroxyl metabolite formation have not
      been identified. In this study, we used human liver microsomes and recombinant
      cytochrome P450s (P450s) to characterize the enzymes involved in the formation of
      hydroxyalbendazole and hydroxyfenbendazole from albendazole and fenbendazole,
      respectively. Of the 10 recombinant P450s, CYP2J2 and/or CYP2C19 was the
      predominant enzyme catalyzing the hydroxylation of albendazole and fenbendazole.
      Albendazole hydroxylation to hydroxyalbendazole is primarily mediated by CYP2J2
      (0.34 MUl/min/pmol P450, which is a rate 3.9- and 8.1-fold higher than the rates
      for CYP2C19 and CYP2E1, respectively), whereas CYP2C19 and CYP2J2 contributed to
      the formation of hydroxyfenbendazole from fenbendazole (2.68 and 1.94
      MUl/min/pmol P450 for CYP2C19 and CYP2J2, respectively, which are rates 11.7- and
      8.4-fold higher than the rate for CYP2D6). Correlation analysis between the known
      P450 enzyme activities and the rate of hydroxyalbendazole and hydroxyfenbendazole
      formation in samples from 14 human liver microsomes showed that albendazole
      hydroxylation correlates with CYP2J2 activity and fenbendazole hydroxylation
      correlates with CYP2C19 and CYP2J2 activities. These findings were supported by a
      P450 isoform-selective inhibition study in human liver microsomes. In conclusion,
      our data for the first time suggest that albendazole hydroxylation is primarily
      catalyzed by CYP2J2, whereas fenbendazole hydroxylation is preferentially
      catalyzed by CYP2C19 and CYP2J2. The present data will be useful in understanding
      the pharmacokinetics and drug interactions of albendazole and fenbendazole in
      vivo. 

PMID- 23959308
TI  - Molecular resistance mechanisms of macrolide-resistant invasive Streptococcus
      pneumoniae isolates from Alaska, 1986 to 2010.
AB  - The rapid emergence of antibiotic-resistant pneumococcal strains has reduced
      treatment options. The aim of this study was to determine antimicrobial
      susceptibilities, serotype distributions, and molecular resistance mechanisms
      among macrolide-resistant invasive pneumococcal isolates in Alaska from 1986 to
      2010. We identified cases of invasive pneumococcal disease in Alaska from 1986 to
      2010 through statewide population-based laboratory surveillance. All invasive
      pneumococcal isolates submitted to the Arctic Investigations Program laboratory
      were confirmed by standard microbiological methods and serotyped by slide
      agglutination and the Quellung reaction. MICs were determined by the broth
      microdilution method, and macrolide-resistant genotypes were determined by
      multiplex PCR. Among 2,923 invasive pneumococcal isolates recovered from 1986 to
      2010, 270 (9.2%) were nonsusceptible to erythromycin; 177 (66%) erythromycin
      nonsusceptible isolates demonstrated coresistance to penicillin, and 167 (62%)
      were multidrug resistant. The most frequent serotypes among the macrolide
      resistant isolates were serotypes 6B (23.3%), 14 (20.7%), 19A (16.7%), 9V (8.9%),
      19F (6.3%), 6A (5.6%), and 23F (4.8%). mef and erm(B) genes were detected in 207
      (77%) and 32 (12%) of the isolates, respectively. Nineteen (7%) of the
      erythromycin-nonsusceptible isolates contained both mef and erm(B) genotypes; 15
      were of serotype 19A. There was significant year-to-year variation in the
      proportion of isolates that were nonsusceptible to erythromycin (P < 0.001).
      Macrolide resistance among pneumococcal isolates from Alaska is mediated
      predominantly by mef genes, and this has not changed significantly over time.
      However, there was a statistically significant increase in the proportion of
      isolates that possess both erm(B) and mef, primarily due to serotype 19A
      isolates. 

PMID- 23959309
TI  - Determination of isavuconazole susceptibility of Aspergillus and Candida species
      by the EUCAST method.
AB  - Isavuconazole is a novel expanded-spectrum triazole, which has recently been
      approved by the FDA as an orphan drug to treat invasive aspergillosis and is
      currently being studied in phase III clinical trials for invasive candidiasis.
      The susceptibility of relatively few clinical isolates has been reported. In this
      study, the isavuconazole susceptibilities of 1,237 Aspergillus and 2,010 Candida
      geographically diverse clinical isolates were determined by EUCAST methodology at
      four European mycology laboratories, producing the largest multicenter data set
      thus far for this compound. In addition, a blinded collection of 30 cyp51A mutant
      Aspergillus fumigatus clinical isolates and 10 wild-type isolates was tested.
      From these two data sets, the following preliminary epidemiological cutoff
      (ECOFF) values were suggested: 2 mg/liter for Aspergillus fumigatus, Aspergillus
      terreus, and Aspergillus flavus; 4 mg/liter for Aspergillus niger; 0.25 mg/liter
      for Aspergillus nidulans; and 0.03 mg/liter for Candida albicans, Candida
      parapsilosis, and Candida tropicalis. Unfortunately, ECOFFs could not be
      determined for Candida glabrata or Candida krusei due to an unexplained
      interlaboratory MIC variation. For the blinded collection of A. fumigatus
      isolates, all MICs were <=2 mg/liter for wild-type isolates. Differential
      isavuconazole MICs were observed for triazole-resistant A. fumigatus isolates
      with different cyp51A alterations: TR34/L98H mutants had elevated isavuconazole
      MICs, whereas isolates with G54 and M220 alterations had MICs in the wild-type
      range, suggesting that the efficacy of isavuconazole may not be affected by these
      alterations. This study will be an aid in interpreting isavuconazole MICs for
      clinical care and an important step in the future process of setting official
      clinical breakpoints. 

PMID- 23959310
TI  - Whole-genome sequencing of gentamicin-resistant Campylobacter coli isolated from
      U.S. retail meats reveals novel plasmid-mediated aminoglycoside resistance genes.
AB  - Aminoglycoside resistance in Campylobacter has been routinely monitored in the
      United States in clinical isolates since 1996 and in retail meats since 2002.
      Gentamicin resistance first appeared in a single human isolate of Campylobacter
      coli in 2000 and in a single chicken meat isolate in 2007, after which it
      increased rapidly to account for 11.3% of human isolates and 12.5% of retail
      isolates in 2010. Pulsed-field gel electrophoresis analysis indicated that
      gentamicin-resistant C. coli isolates from retail meat were clonal. We sequenced
      the genomes of two strains of this clone using a next-generation sequencing
      technique in order to investigate the genetic basis for the resistance. The gaps
      of one strain were closed using optical mapping and Sanger sequencing, and this
      is the first completed genome of C. coli. The two genomes are highly similar to
      each other. A self-transmissible plasmid carrying multiple antibiotic resistance
      genes was revealed within both genomes, carrying genes encoding resistance to
      gentamicin, kanamycin, streptomycin, streptothricin, and tetracycline.
      Bioinformatics analysis and experimental results showed that gentamicin
      resistance was due to a phosphotransferase gene, aph(2")-Ig, not described
      previously. The phylogenetic relationship of this newly emerged clone to other
      Campylobacter spp. was determined by whole-genome single nucleotide polymorphisms
      (SNPs), which showed that it clustered with the other poultry isolates and was
      separated from isolates from livestock.

PMID- 23959311
TI  - Oral DAV131, a charcoal-based adsorbent, inhibits intestinal colonization by beta
      lactam-resistant Klebsiella pneumoniae in cefotaxime-treated mice.
AB  - Antibiotics excreted into the intestinal tract, such as broad-spectrum
      cephalosporins, disrupt the indigenous microflora, affect colonization resistance
      (CR), and promote intestinal colonization by resistant bacteria. We tested
      whether oral DAV131, a charcoal-based adsorbent, would prevent colonization by a
      cefotaxime (CTX)-resistant Klebsiella pneumoniae strain (PUG-2) in CTX-treated
      mice. Mice received CTX, saline, CTX and DAV131, or saline and DAV131 for 3 days
      before oral challenge with 10(6) CFU of PUG-2. The fecal CTX concentrations and
      counts of PUG-2 were assayed. Fecal CTX disappeared when DAV131 was given
      concomitantly with CTX (P < 0.05), and the area under the curve of PUG-2 fecal
      density was significantly reduced (P < 0.01). In conclusion, reducing intestinal
      antibiotic exposure with DAV131 may reduce colonization by resistant strains
      during treatment compared to treatment with CTX only. This might open new
      possibilities for decreasing the impact of antibiotics on the intestinal
      microbiota during treatments. 

PMID- 23959312
TI  - The mevalonate auxotrophic mutant of Staphylococcus aureus can adapt to
      mevalonate depletion.
AB  - In this study, we attempted to adopt the auxotrophic mevalonate synthase mutant
      (DeltamvaS mutant) of Staphylococcus aureus to study whether a nongrowing but
      viable cell population is tolerant to bactericidal antibiotics. The mevalonate
      depleted nongrowing DeltamvaS mutant was found tolerant to antibiotics.
      Surprisingly, after prolonged cultivation, we obtained stable DeltamvaS variants
      that were able to grow without mevalonate, which suggested unknown mechanisms for
      compensating undecaprenyl pyrophosphate production without mevalonate in S.
      aureus. 

PMID- 23959313
TI  - Menaquinone analogs inhibit growth of bacterial pathogens.
AB  - Gram-positive bacteria cause serious human illnesses through combinations of cell
      surface and secreted virulence factors. We initiated studies with four of these
      organisms to develop novel topical antibacterial agents that interfere with
      growth and exotoxin production, focusing on menaquinone analogs. Menadione, 1,4
      naphthoquinone, and coenzymes Q1 to Q3 but not menaquinone, phylloquinone, or
      coenzyme Q10 inhibited the growth and to a greater extent exotoxin production of
      Staphylococcus aureus, Bacillus anthracis, Streptococcus pyogenes, and
      Streptococcus agalactiae at concentrations of 10 to 200 MUg/ml. Coenzyme Q1
      reduced the ability of S. aureus to cause toxic shock syndrome in a rabbit model,
      inhibited the growth of four Gram-negative bacteria, and synergized with another
      antimicrobial agent, glycerol monolaurate, to inhibit S. aureus growth. The
      staphylococcal two-component system SrrA/B was shown to be an antibacterial
      target of coenzyme Q1. We hypothesize that menaquinone analogs both induce toxic
      reactive oxygen species and affect bacterial plasma membranes and biosynthetic
      machinery to interfere with two-component systems, respiration, and
      macromolecular synthesis. These compounds represent a novel class of potential
      topical therapeutic agents. 

PMID- 23959314
TI  - Fosfomycin and tobramycin in combination downregulate nitrate reductase genes
      narG and narH, resulting in increased activity against Pseudomonas aeruginosa
      under anaerobic conditions.
AB  - The activity of aminoglycosides, which are used to treat Pseudomonas aeruginosa
      respiratory infection in cystic fibrosis (CF) patients, is reduced under the
      anaerobic conditions that reflect the CF lung in vivo. In contrast, a 4:1 (wt/wt)
      combination of fosfomycin and tobramycin (F:T), which is under investigation for
      use in the treatment of CF lung infection, has increased activity against P.
      aeruginosa under anaerobic conditions. The aim of this study was to elucidate the
      mechanisms underlying the increased activity of F:T under anaerobic conditions.
      Microarray analysis was used to identify the transcriptional basis of increased
      F:T activity under anaerobic conditions, and key findings were confirmed by
      microbiological tests, including nitrate utilization assays, growth curves, and
      susceptibility testing. Notably, growth in subinhibitory concentrations of F:T,
      but not tobramycin or fosfomycin alone, significantly downregulated (P < 0.05)
      nitrate reductase genes narG and narH, which are essential for normal anaerobic
      growth of P. aeruginosa. Under anaerobic conditions, F:T significantly decreased
      (P < 0.001) nitrate utilization in P. aeruginosa strains PAO1, PA14, and PA14
      lasR::Gm, a mutant known to exhibit increased nitrate utilization. A similar
      effect was observed with two clinical P. aeruginosa isolates. Growth curves
      indicate that nitrate reductase transposon mutants had reduced growth under
      anaerobic conditions, with these mutants also having increased susceptibility to
      F:T compared to the wild type under similar conditions. The results of this study
      suggest that downregulation of nitrate reductase genes resulting in reduced
      nitrate utilization is the mechanism underlying the increased activity of F:T
      under anaerobic conditions. 

PMID- 23959315
TI  - Antimicrobial susceptibility pattern and epidemiology of female urinary tract
      infections in South Korea, 2010-2011.
AB  - This study aimed to (i) investigate the antimicrobial susceptibilities of
      bacteria that cause urinary tract infections (UTIs) in outpatient and inpatient
      settings and (ii) evaluate the risk factors for emerging antimicrobial drug
      resistance in UTIs in South Korea. In total, 3,023 samples without duplication
      were collected from females between 25 and 65 years of age who had been diagnosed
      with a urinary tract infection. Multicenter patient data were collected using a
      Web-based electronic system and then evaluated. The isolation rates of
      Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecium in the
      outpatient setting were 78.1, 4.7, and 1.3%, respectively; in the inpatient
      setting, the isolation rates of these microorganisms were 37.8, 9.9, and 14.8%,
      respectively. The susceptibilities of E. coli to amikacin, amoxicillin-clavulanic
      acid, cefotaxime, cefoxitin, ciprofloxacin, piperacillin-tazobactam, and imipenem
      in the outpatient setting were 99.4, 79.8, 89.4, 92.8, 69.8, 96.9, and 100.0%,
      respectively; in the inpatient setting, the susceptibilities to these antibiotics
      were 97.8, 73.9, 73.7, 82.1, 53.6, 93.2, and 100.0%, respectively. The most
      unique and common risk factor for emerging antimicrobial-resistant E. coli, K.
      pneumoniae, and E. faecium was previous exposure to antimicrobials. On the basis
      of these data, the use of fluoroquinolones should be reserved until culture data
      are available for the treatment of UTIs in South Korea. The present study will
      serve as a useful reference for Far Eastern Asia. 

PMID- 23959316
TI  - Kallistatin modulates immune cells and confers anti-inflammatory response to
      protect mice from group A streptococcal infection.
AB  - Group A streptococcus (GAS) infection may cause severe life-threatening diseases,
      including necrotizing fasciitis and streptococcal toxic shock syndrome. Despite
      the availability of effective antimicrobial agents, there has been a worldwide
      increase in the incidence of invasive GAS infection. Kallistatin (KS), originally
      found to be a tissue kallikrein-binding protein, has recently been shown to
      possess anti-inflammatory properties. However, its efficacy in microbial
      infection has not been explored. In this study, we transiently expressed the
      human KS gene by hydrodynamic injection and investigated its anti-inflammatory
      and protective effects in mice via air pouch inoculation of GAS. The results
      showed that KS significantly increased the survival rate of GAS-infected mice. KS
      treatment reduced local skin damage and bacterial counts compared with those in
      mice infected with GAS and treated with a control plasmid or saline. While there
      was a decrease in immune cell infiltration of the local infection site, cell
      viability and antimicrobial factors such as reactive oxygen species actually
      increased after KS treatment. The efficiency of intracellular bacterial killing
      in neutrophils was directly enhanced by KS administration. Several inflammatory
      cytokines, including tumor necrosis factor alpha, interleukin 1beta, and
      interleukin 6, in local infection sites were reduced by KS. In addition, KS
      treatment reduced vessel leakage, bacteremia, and liver damage after local
      infection. Therefore, our study demonstrates that KS provides protection in GAS
      infected mice by enhancing bacterial clearance, as well as reducing inflammatory
      responses and organ damage. 

PMID- 23959317
TI  - Improving the lethal effect of cpl-7, a pneumococcal phage lysozyme with broad
      bactericidal activity, by inverting the net charge of its cell wall-binding
      module.
AB  - Phage endolysins are murein hydrolases that break the bacterial cell wall to
      provoke lysis and release of phage progeny. Recently, these enzymes have also
      been recognized as powerful and specific antibacterial agents when added
      exogenously. In the pneumococcal system, most cell wall associated murein
      hydrolases reported so far depend on choline for activity, and Cpl-7 lysozyme
      constitutes a remarkable exception. Here, we report the improvement of the
      killing activity of the Cpl-7 endolysin by inversion of the sign of the charge of
      the cell wall-binding module (from -14.93 to +3.0 at neutral pH). The engineered
      variant, Cpl-7S, has 15 amino acid substitutions and an improved lytic activity
      against Streptococcus pneumoniae (including multiresistant strains),
      Streptococcus pyogenes, and other pathogens. Moreover, we have demonstrated that
      a single 25-MUg dose of Cpl-7S significantly increased the survival rate of
      zebrafish embryos infected with S. pneumoniae or S. pyogenes, confirming the
      killing effect of Cpl-7S in vivo. Interestingly, Cpl-7S, in combination with
      0.01% carvacrol (an essential oil), was also found to efficiently kill Gram
      negative bacteria such as Escherichia coli and Pseudomonas putida, an effect not
      described previously. Our findings provide a strategy to improve the lytic
      activity of phage endolysins based on facilitating their pass through the
      negatively charged bacterial envelope, and thereby their interaction with the
      cell wall target, by modulating the net charge of the cell wall-binding modules. 

PMID- 23959318
TI  - Adaptation of Enterococcus faecalis to daptomycin reveals an ordered progression
      to resistance.
AB  - With increasing numbers of hospital-acquired antibiotic resistant infections each
      year and staggering health care costs, there is a clear need for new
      antimicrobial agents, as well as novel strategies to extend their clinical
      efficacy. While genomic studies have provided a wealth of information about the
      alleles associated with adaptation to antibiotics, they do not provide essential
      information about the relative importance of genomic changes, their order of
      appearance, or potential epistatic relationships between adaptive changes. Here
      we used quantitative experimental evolution of a single polymorphic population in
      continuous culture with whole-genome sequencing and allelic frequency
      measurements to study daptomycin (DAP) resistance in the vancomycin-resistant
      clinical pathogen Enterococcus faecalis S613. Importantly, we sustained both
      planktonic and nonplanktonic (i.e., biofilm) populations in coculture as the
      concentration of antibiotic was raised, facilitating the development of more
      ecological complexity than is typically observed in laboratory evolution.
      Quantitative experimental evolution revealed a clear order and hierarchy of
      genetic changes leading to resistance, the signaling and metabolic pathways
      responsible, and the relative importance of these mutations to the evolution of
      DAP resistance. Despite the relative simplicity of this ex vivo approach compared
      to the ecological complexity of the human body, we showed that experimental
      evolution allows for rapid identification of clinically relevant adaptive
      molecular pathways and new targets for drug design in pathogens. 

PMID- 23959319
TI  - Clinical pharmacodynamic index identification for micafungin in esophageal
      candidiasis: dosing strategy optimization.
AB  - Echinocandins exhibit concentration-dependent effects on Candida species, and
      preclinical studies support the administration of large, infrequent doses. The
      current report examines the pharmacokinetics/pharmacodynamics of two multicenter,
      randomized trials of micafungin dosing regimens that differed in both dose level
      and dosing interval. Analysis demonstrates the clinical relevance of the dose
      level and area under the concentration-time curve (AUC). Better, although not
      statistically significant (P = 0.056), outcomes were seen with higher maximum
      concentrations of drug in serum (Cmax) and large, infrequent doses. The results
      support further clinical investigation of novel micafungin dosing regimens with
      large doses but less than daily administration. (These studies have been
      registered at ClinicalTrials.gov under registration no. NCT00666185 and
      NCT00665639.). 

PMID- 23959320
TI  - In vitro efficacies and resistance profiles of rifampin-based combination
      regimens for biofilm-embedded methicillin-resistant Staphylococcus aureus.
AB  - To compare the in vitro antibacterial efficacies and resistance profiles of
      rifampin-based combinations against methicillin-resistant Staphylococcus aureus
      (MRSA) in a biofilm model, the antibacterial activities of vancomycin,
      teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and
      tigecycline alone or in combination with rifampin against biofilm-embedded MRSA
      were measured. The rifampin-resistant mutation frequencies were evaluated. Of the
      rifampin-based combinations, rifampin enhances the antibacterial activities of
      and even synergizes with fusidic acid, tigecycline, and, to a lesser extent,
      linezolid, fosfomycin, and minocycline against biofilm-embedded MRSA. Such
      combinations with weaker rifampin resistance induction activities may provide a
      therapeutic advantage in MRSA biofilm-related infections. 

PMID- 23959321
TI  - Risk factors for treatment failure of polymyxin B monotherapy for carbapenem
      resistant Klebsiella pneumoniae infections.
AB  - Polymyxins are reserved for salvage therapy of infections caused by carbapenem
      resistant Klebsiella pneumoniae (CRKP). Though synergy has been demonstrated for
      the combination of polymyxins with carbapenems or tigecycline, in vitro synergy
      tests are nonstandardized, and the clinical effect of synergy remains unclear.
      This study describes outcomes for patients with CRKP infections who were treated
      with polymyxin B monotherapy. We retrospectively reviewed the medical records of
      patients with CRKP infections who received polymyxin B monotherapy from 2007 to
      2011. Clinical, microbiology, and antimicrobial treatment data were collected.
      Risk factors for treatment failure were identified by logistic regression. Forty
      patients were included in the analysis. Twenty-nine of 40 (73%) patients achieved
      clinical cure as defined by clinician-documented improvement in signs and
      symptoms of infections, and 17/32 (53%) patients with follow-up culture data
      achieved microbiological cure. End-of-treatment mortality was 10%, and 30-day
      mortality was 28%. In a multivariate analysis, baseline renal insufficiency was
      associated with a 6.0-fold increase in clinical failure after adjusting for
      septic shock (odds ratio [OR] = 6.0; 95% confidence interval [CI] = 1.22 to
      29.59). Breakthrough infections with organisms intrinsically resistant to
      polymyxins occurred in 3 patients during the treatment. Eighteen of 40 (45%)
      patients developed a new CRKP infection a median of 23 days after initial
      polymyxin B treatment, and 3 of these 18 infections were polymyxin resistant. The
      clinical cure rate achieved in this retrospective study was 73% of patients with
      CRKP infections treated with polymyxin B monotherapy. Baseline renal
      insufficiency was a risk factor for treatment failure after adjusting for septic
      shock. Breakthrough infections with organisms intrinsically resistant to
      polymyxin B and development of resistance to polymyxin B in subsequent CRKP
      isolates are of concern. 

PMID- 23959322
TI  - Impact of in vivo triazole and echinocandin combination therapy for invasive
      pulmonary aspergillosis: enhanced efficacy against Cyp51 mutant isolates.
AB  - Previous studies examining combination therapy for invasive pulmonary
      aspergillosis (IPA) have revealed conflicting results, including antagonism,
      indifference, and enhanced effects. The most commonly employed combination for
      this infection includes a mold-active triazole and echinocandin. Few studies have
      evaluated combination therapy from a pharmacodynamic (PD) perspective, and even
      fewer have examined combination therapy against both wild-type and azole
      resistant Cyp51 mutant isolates. The current studies aim to fill this gap in
      knowledge. Four Aspergillus fumigatus isolates were utilized, including a wild
      type strain, an Fks1 mutant (posaconazole susceptible and caspofungin resistant),
      and two Cyp51 mutants (posaconazole resistant). A neutropenic murine model of IPA
      was used for the treatment studies. The dosing design included monotherapy with
      posaconazole, monotherapy with caspofungin, and combination therapy with both.
      Efficacy was determined using quantitative PCR, and results were normalized to
      known quantities of conidia (conidial equivalents [CE]). The static dose, 1-log
      kill dose, and associated PD target area under the curve (AUC)/MIC ratio were
      determined for monotherapy and combination therapy. Monotherapy experiments
      revealed potent activity for posaconazole, with reductions of 3 to 4 log10
      Aspergillus CE/ml with the two "low"-MIC isolates. Posaconazole alone was less
      effective for the two isolates with higher MICs. Caspofungin monotherapy did not
      produce a significant decrease in fungal burden for any strain. Combination
      therapy with the two antifungals did not enhance efficacy for the two
      posaconazole-susceptible isolates. However, the drug combination produced
      synergistic activity against both posaconazole-resistant isolates. Specifically,
      the combination resulted in a 1- to 2-log10 decline in burden that would not have
      been predicted based on the monotherapy results for each drug. This corresponded
      to a reduction in the free-drug posaconazole AUC/MIC ratio needed for stasis of
      up to 17-fold. The data suggest that combination therapy using a triazole and an
      echinocandin may be a beneficial treatment strategy for triazole-resistant
      isolates. 

PMID- 23959323
TI  - Exploration of health status, healthcare utilization, and health service
      expectations among Taiwanese adolescents.
AB  - There have been few reports about adolescent experiences with and expectations of
      health service utilization in an Asian societal setting. The aim of this study is
      to analyze the use of healthcare services in relation to health status and
      explore adolescents' preferences for youth-friendly service among Taiwanese high
      school students. A cross-sectional questionnaire-based survey was conducted on
      Taiwanese adolescents aged 12-18 years in 2010.We invited participants to rate
      their health status, report their previous healthcare service use, and rank their
      health service preferences.We used logistic regression analysis to investigate
      the association between self-rated health status and healthcare utilization and
      used nonparametric analysis to compare health service preferences among
      sociodemographic subgroups. A total of 4,907 students (97.2 % response rate)
      returned valid questionnaires for analysis. Poor health status and chronic
      illness were most salient factors independently associated with frequent
      healthcare service use. Only 40 % of respondents reported having a regular
      doctor, and pediatrics (57.7 %) was the most commonly identified professional
      source of medical care. A great majority (86.2 %) of respondents made clinical
      visits with parents. For characteristics of youth-friendly clinician, the top
      ranked items included competency and patience, while having helpful and friendly
      personnel was highlighted for clinical setting. CONCLUSION: Family participation
      is critical in healthcare for adolescents in Asian cultures. Health service use
      is significantly influenced by health status and chronic illness in the general
      health insurance system. Understanding these background influences on
      expectations for healthcare may help to create youth-friendly health services
      that are more culturally appropriate.

PMID- 23959324
TI  - Vitamin D status and predictors of hypovitaminosis D in Italian children and
      adolescents: a cross-sectional study.
AB  - Hypovitaminosis D affects children and adolescents all around the world. Italian
      data on vitamin D status and risk factors for hypovitaminosis D during pediatric
      age are lacking. Six hundred fifty-two children and adolescents (range 2.0-21.0
      years) living in the northwestern area of Tuscany were recruited at the
      Department of Pediatrics, University Hospital Pisa. None of them had received
      vitamin D supplementation in the previous 12 months. 25-hydroxyvitamin D (25-OH
      D) and parathyroid hormone (PTH) levels were analyzed in all subjects. Severe
      vitamin D deficiency was defined as serum levels of 25-OH-D<25.0 nmol/L (10.0
      ng/mL) and vitamin D deficiency a<50.0 nmol/L (20.0 ng/mL). Serum 25-OH-D levels
      of 50.0-74.9 nmol/L (20.0-29.9 ng/mL) indicated vitamin D insufficiency, whereas
      25-OH-D levels >= 75.0 nmol/L (30.0 ng/mL) were considered sufficient.
      Hypovitaminosis D was defined as 25-OH-D levels<75.0 nmol/L (30.0 ng/mL). The
      median serum 25-OH-D level was 51.8 nmol/L, range 6.7-174.7 (20.7 ng/mL, range
      2.7-70.0), with a prevalence of vitamin D deficiency, insufficiency, and
      sufficiency of 45.9, 33.6, and 20.5 %, respectively. The prevalence of severe
      vitamin D deficiency was 9.5 %. Adolescents had lower median 25-OH-D levels (49.8
      nmol/L, range 8.1-174.7; 20.0 ng/mL, range 3.2-70.0) than children (55.6 nmol/L,
      range 6.8-154.6; 22.3 ng/mL, range 2.7-61.9, p=0.006). Non-white individuals
      (n=37) had median serum 25-OH-D levels in the range of deficiency (28.2 nmol/L,
      range 8.1-86.2; 11.3 ng/mL, range 3.2-34.5), with 36/37 having hypovitaminosis D.
      Logistic regression showed significant increased risk of hypovitaminosis D in the
      following: blood samples taken in winter (odds ratio (OR) 27.20), spring (OR
      26.44), and fall (OR 8.27) compared to summer; overweight (OR 5.02) and obese (OR
      5.36) subjects compared to individuals with normal BMI; low sun exposure (OR
      8.64) compared to good exposure, and regular use of sunscreens (OR 7.06) compared
      to non-regular use. Gender and place of residence were not associated with
      vitamin D status. The 25-OH-D levels were inversely related to the PTH levels (r=
      0.395, p<0.0001). Sixty-three out of the 652 (9.7 %) subjects showed secondary
      hyperparathyroidism. CONCLUSION: Italian children and adolescents who were not
      receiving vitamin D supplementation had high prevalence of hypovitaminosis D.
      Careful identification of factors affecting vitamin D status is advisable to
      promptly start vitamin D supplementation in children and adolescents.

PMID- 23959325
TI  - Generalized joint hypermobility and voiding dysfunction in children: is there any
      relationship?
AB  - Voiding dysfunction is a common entity in pediatric urology. It is believed to
      have a multifactorial etiology. The aim of this study was to investigate whether
      there is an increased prevalence of generalized joint hypermobility (GJH) in
      children with voiding dysfunction compared to normal children. Moreover, the
      prevalence of voiding complaints in patients with and without GJH was assessed. A
      total of 226 children--aged 5 to 14 years--including 113 patients diagnosed with
      voiding dysfunction and 113 sex/age/body mass index-matched normal children were
      recruited. GJH was evaluated in both groups using the Beighton score (4 or more=
      hypermobile). In the patient's group, GJH was significantly more frequent than in
      controls: 51/113 (45 %) versus 19/113 (17 %) (P=0.001). In addition, in both
      groups, GJH was more prominent in girls than boys (P<0.05). Urinary tract
      infection was the most frequent features in children with voiding dysfunction (64
      %). In the subgroup of positive GJH, urinary tract infection remained the most
      common manifestation among the girls (P=0.003), while constipation was the most
      prevalent manifestation among the boys (P=0.001). CONCLUSION: Our findings
      suggest that children with voiding dysfunction have significantly higher
      prevalence of GJH compared to normal children. Further studies are needed to
      determine the cause and effect of these two common presentations and will help to
      develop a multidisciplinary approach in understanding and management of voiding
      dysfunction in children.

PMID- 23959326
TI  - Depression and adherence to treatment in diabetic children and adolescents: a
      systematic review and meta-analysis of observational studies.
AB  - Depression compromises diabetes treatment in juveniles, and this study aimed to
      identify influential targets most likely to improve adherence to treatment and
      glycemic control. Prospective observational studies investigating associations
      between depression and treatment adherence in juveniles with type 1 diabetes were
      extracted from MEDLINE, EMBASE, CINAHL, PsycINFO and Cochrane Central. Nineteen
      studies comprising 2,935 juveniles met our criteria. Median effect sizes between
      depression and treatment adherence were 0.22 (interquartile range (IQR), 0.16
      0.35) by patient and 0.13 (IQR, 0.12-0.24) caregiver report. Corresponding values
      for depression/glycemic control were 0.16 (IQR, 0.09- 0.23) and 0.08 (IQR, 0.04
      0.14), respectively. Effect sizes varied with study design, publication year and
      assessment tools: CES-D yielded a higher effect size than other assessment tools
      for depression, where associations for depression and either adherence or
      glycemic control was investigated. Several behaviours influenced adherence and
      glycemic control. CONCLUSION: This study showed moderate associations between
      depression and poor treatment adherence. Targeting behaviour and social
      environments, however, may ultimately provide more cost-effective health gains
      than targeting depressive symptoms.

PMID- 23959327
TI  - Adolescent health care transition in transition.

PMID- 23959329
TI  - Morphology and atomic-scale structure of single-layer WS2 nanoclusters.
AB  - Two-dimensional sheets of transition metal (Mo and W) sulfides are attracting
      strong attention due to the unique electronic and optical properties associated
      with the material in its single-layer form. The single-layer MoS2 and WS2 are
      already in widespread commercial use in catalytic applications as both
      hydrotreating and hydrocracking catalysts. Consequently, characterization of the
      morphology and atomic structure of such particles is of utmost importance for the
      understanding of the catalytic active phase. However, in comparison with the
      related MoS2 system only little is known about the fundamental properties of
      single-layer WS2 (tungstenite). Here, we use an interplay of atom-resolved
      Scanning Tunneling Microscopy (STM) studies of Au(111)-supported WS2
      nanoparticles and calculated edge structures using Density Functional Theory
      (DFT) to reveal the equilibrium morphology and prevalent edge structures of
      single-layer WS2. The STM results reveal that the single layer S-W-S sheets adopt
      a triangular equilibrium shape under the sulfiding conditions of the synthesis,
      with fully sulfided edges. The predominant edge structures are determined to be
      the (101[combining macron]0) W-edge, but for the smallest nanoclusters also the
      (1[combining macron]010) S-edges become important. DFT calculations are used to
      construct phase diagrams of the WS2 edges, and describe their sulfur and hydrogen
      coordination under different conditions, and in this way shed light on the
      catalytic role of WS2 edges. 

PMID- 23959328
TI  - Viral subversion of the nuclear pore complex.
AB  - The nuclear pore complex (NPC) acts as a selective barrier between the nucleus
      and the cytoplasm and is responsible for mediating communication by regulating
      the transport of RNA and proteins. Numerous viral pathogens have evolved
      different mechanisms to hijack the NPC in order to regulate trafficking of viral
      proteins, genomes and even capsids into and out of the nucleus thus promoting
      virus replication. The present review examines the different strategies and the
      specific nucleoporins utilized during viral infections as a means of promoting
      their life cycle and inhibiting host viral defenses. 

PMID- 23959331
TI  - [TraumaregisterTraumaNetwork DGU(r) und TraumaRegister DGU(r). Success by
      cooperation and documentation].
AB  - BACKGROUND: The TraumaNetwork DGU(r) (TNW) connects hospitals with different
      capacities for the treatment of severely injured patients who work together as
      superregional (STC), regional (RTC) and local trauma centres (LTC). The standards
      of treatment and equipment are defined on the basis of current guidelines as
      published in the"White book of the Treatment of Severely Injured Patients". An
      external audit process evaluates the organisation and structure of participating
      hospitals as well as the cooperation of the trauma centres within a regional TNW.
      RESULTS: In May 2013 a total of 618 hospitals were visited and assessed according
      to the White book and 39 fully certified regional TNWs covered around 85% of the
      area of Germany. Treatment quality in the certified TCs was analyzed on the basis
      of 25,249 severely injured patients in the TraumaRegister DGU(r) (2008-2011) and
      significant differences between the expected and observed mortality rates were
      found. These differences were most obvious in superregional and regional trauma
      centres. CONCLUSION: The TraumaNetwork represents an innovative, cooperative
      project for successfully improving the treatment of severely injured patients.

PMID- 23959330
TI  - Intra-subject variability in human bone marrow stromal cell (BMSC) replicative
      senescence: molecular changes associated with BMSC senescence.
AB  - The outcomes of clinical trials using bone marrow stromal cell (BMSC) are
      variable; the degree of the expansion of BMSCs during clinical manufacturing may
      contribute to this variability since cell expansion is limited by senescence.
      Human BMSCs from aspirates of healthy subjects were subcultured serially until
      cell growth stopped. Phenotype and functional measurements of BMSCs from two
      subjects including senescence-associated beta-galactosidase staining and colony
      formation efficiency changed from an early to a senescence pattern at passage 6
      or 7. Transcriptome analysis of 10 early and 15 late passage BMSC samples from 5
      subjects revealed 2122 differentially expressed genes, which were associated with
      immune response, development, and cell proliferation pathways. Analysis of 57
      serial BMSC samples from 7 donors revealed that the change from an early to
      senescent profile was variable among subjects and occurred prior to changes in
      phenotypes. BMSC age expressed as a percentage of maximum population doublings
      (PDs) was a good indicator for an early or senescence transcription signature but
      this measure of BMSC life span can only be calculated after expanding BMSCs to
      senescence. In order to find a more useful surrogate measure of BMSC age, we used
      a computational biology approach to identify a set of genes whose expression at
      each passage would predict elapsed age of BMSCs. A total of 155 genes were highly
      correlated with BMSC age. A least angle regression algorithm identified a set of
      24 BMSC age-predictive genes. In conclusion, the onset of senescence-associated
      molecular changes was variable and preceded changes in other indicators of BMSC
      quality and senescence. The 24 BMSC age predictive genes will be useful in
      assessing the quality of clinical BMSC products. 

PMID- 23959332
TI  - [Long-term results after multiple trauma with ISS >= 25. Outcome and predictors
      of quality of life].
AB  - BACKGROUND: The survival chances of multiple trauma patients have continually
      improved over the last decades; therefore, it is often not a question of whether
      a patient survives a severe accident but rather how the patient survives.
      METHODS: In a retrospective study 127 patients were questioned regarding quality
      of life and health and possible influencing factors using the POLO chart an
      average of 70 months after suffering severe trauma (ISS O 35.6). RESULTS: The
      quality of life of severely injured patients is significantly reduced compared
      with the normal population even years after the trauma. In addition to four
      pretraumatic factors (older age, female gender, low education and previous
      illnesses) four posttraumatic variables (difficulties with
      authorities/institutions and unemployment as a consequence of the accident, long
      duration and subjectively inadequate treatment in hospital) were identified that
      have a negative impact on long-term quality of life. CONCLUSIONS: The self
      reported quality of life after multiple trauma no longer permanently achieves the
      original level despite extensive rehabilitation measures. Post-traumatic factors
      have a greater impact on the long-term quality of life than the injury severity.
      A long-term care and specialized rehabilitation services are needed to improve
      outcome further.

PMID- 23959333
TI  - [14]Heterophane prototypes containing azolium and/or azole anion-binding motifs.
AB  - Revisiting a '3 + 1' convergent stepwise strategy permitted the synthesis of
      [14]imidazoliophane 2.2Br in excellent yield for a macrocyclization. The new
      [14]triazoliophane 3 and bis(1,2,3-triazolium) counterpart 4.2Cl were less
      synthetically accessible and the hybrid derivative 5.Cl proved troublesome to
      prepare. Triazolophane 3 was devoid of anion-binding affinities, while charged
      [14]heterophane prototypes showed a particular preference for acetate. When
      association constants were compared, dicationic systems 2.2PF6 and 4.2PF6 showed
      greater values than monocationic macrocycle 5.PF6, and the highest affinities
      corresponded to the bis(imidazolium) receptor 2.2PF6.

PMID- 23959335
TI  - Gallium nitrate induces fibrinogen flocculation: an explanation for its
      hemostatic effect?
AB  - A novel hemostatic effect of gallium nitrate has recently been discovered. Our
      aim was to perform a preliminary investigation into its mode of action.
      Thromboelastography(r) showed no effect on coagulation but pointed instead to
      changes in fibrinogen concentration. We measured functional fibrinogen in whole
      blood after addition of gallium nitrate and nitric acid. We found that gallium
      nitrate induces fibrinogen precipitation in whole blood to a significantly higher
      degree than solutions of nitric acid alone. This precipitate is not primarily pH
      driven, and appears to occur via flocculation. This behavior is in line with the
      generally observed ability of metals to induce fibrinogen precipitation. Further
      investigation is required into this novel phenomenon.

PMID- 23959334
TI  - PGP 9.5 immunocytochemical staining for pancreatic endocrine tumors.
AB  - AIMS/HYPOTHESIS: Protein gene product 9.5 (PGP 9.5) is a marker for
      neuroendocrine cells but has not been used for pancreatic islet cells and
      pancreatic endocrine tumors (PETs). Antibodies for PGP 9.5 are now commercially
      available for immunocytochemical study, with which immunostaining may be able to
      differentiate between benign and malignant PETs. RESULTS: All 4 kinds of normal
      islet cells were positively immunostained for PGP 9.5-moderately positive for
      beta-cells and strongly positive for delta-cells, whereas ganglion cells were
      immunostained more strongly than islet cells. Nine of 12 insulinomas were
      moderately to strongly positive for PGP 9.5. Two glucagonomas, 3 of 6 pancreatic
      polypeptidomas (PPomas), 3 of 9 gastrinomas, and 2 of 4 non-functioning PETs were
      negative for PGP 9.5. MATERIALS AND METHODS: Thirty-four PETs were
      immunocytochemically stained for PGP 9.5 using a rabbit polyclonal antibody
      together with immunostaining for 4 pancreatic hormones, chromogranin A (CgA), and
      gastrin. PETs consisted of 12 insulinomas, 2 glucagonomas, 1 somatostatinoma
      (SRIFoma), 6 PPomas, 9 gastrinomas, and 4 non-functioning PETs.
      CONCLUSION/INTERPRETATION: PGP 9.5 immunostaining was universally positive for 4
      kinds of islet cells and was moderately to strongly positive for 9 of 12 (75%)
      insulinomas. All 22 non-beta-cell PETs were negative or weakly positive for PGP
      9.5, and thus negative or weakly positive PGP 9.5 immunostaining may be used as a
      marker for potential malignancy and poor prognosis for non-beta-cell PETs.

PMID- 23959336
TI  - One-step synthesis of protein-encapsulated microspheres in a porous scaffold by
      freeze-drying double emulsions and tuneable protein release.
AB  - A one-step method is developed to prepare BSA-encapsulated PLGA microspheres in
      porous chitosan via freeze-drying water-in-oil-in-water emulsions. Tuneable BSA
      release is demonstrated. 

PMID- 23959337
TI  - Novel prediction score including pre- and intraoperative parameters best predicts
      acute kidney injury after liver surgery.
AB  - BACKGROUND: A recently published score predicts the occurrence of acute kidney
      injury (AKI) after liver resection based on preoperative parameters (chronic
      renal failure, cardiovascular disease, diabetes, and alanine-aminotransferase
      levels). By inclusion of additional intraoperative parameters we aimed to develop
      a new prediction model. METHODS: A series of 549 consecutive patients were
      enrolled. The preoperative score and intraoperative parameters (blood
      transfusion, hepaticojejunostomy, oliguria, cirrhosis, diuretics, colloids, and
      catecholamine) were included in a multivariate logistic regression model. We
      added the strongest predictors that improved prediction of AKI compared to the
      existing score. An internal validation by fivefold cross validation was
      performed, followed by a decision curve analysis to evaluate unnecessary special
      care unit admissions. RESULTS: Blood transfusions, hepaticojejunostomy, and
      oliguria were the strongest intraoperative predictors of AKI after liver
      resection. The new score ranges from 0 to 64 points predicting postoperative AKI
      with a probability of 3.5-95 %. Calibration was good in both models (15 %
      predicted risk vs. 15 % observed risk). The fivefold cross-validation indicated
      good accuracy of the new model (AUC 0.79 (95 % CI 0.73-0.84)). Discrimination was
      substantially higher in the new model (AUCnew 0.81 (95 % CI 0.76-0.86) versus
      AUCpreoperative 0.60 (95 % CI 0.52-0.69), p < 0.001). The new score could reduce
      up to 84 unnecessary special care unit admissions per 100 patients depending on
      the decision threshold. CONCLUSIONS: By combining three intraoperative parameters
      with the existing preoperative risk score, a new prediction model was developed
      that more accurately predicts postoperative AKI. It may reduce unnecessary
      admissions to the special care unit and support management of patients at higher
      risk.

PMID- 23959338
TI  - Value of diagnostic and therapeutic laparoscopy for abdominal stab wounds: reply.

PMID- 23959339
TI  - Hepatectomy in elderly patients: does age matter?
AB  - BACKGROUND: With the increase in average life expectancy in recent decades, the
      proportion of elderly patients requiring liver surgery is rising. The aim of the
      meta-analysis reported here was to evaluate the safety and efficacy of
      hepatectomy in elderly patients. METHODS: An extensive electronic search was
      performed for relevant articles that compare the outcomes of hepatectomy in
      patients >=70 years of age with those in younger patients prior to October 2012.
      Analysis of pooled data was performed with RevMan 5.0. RESULTS: Twenty-eight
      observational studies involving 15,480 patients were included in the analysis.
      Compared with the younger patients, elderly patients experienced more
      complications (31.8 vs 28.7 %; P = 0.002), mainly as a result of increased
      cardiac complications (7.5 vs 1.9 %; P < 0.001) and delirium (11.7 vs 4.5 %; P <
      0.001). Postoperative major surgical complications (12.6 vs 11.3 %; P = 0.55) and
      mortality (3.6 vs 3.3 %; P = 0.68) were comparable between elderly and younger
      patients. For patients with malignancies, both the 5-year disease-free survival
      (26.5 vs 26.3 %; P = 0.60) and overall survival (39.5 vs 40.7 %; P = 0.29) did
      not differ significantly between the two groups. CONCLUSIONS: Postoperative major
      surgical complications, mortality, and long-term results in elderly patients seem
      to be comparable with those in younger patients, suggesting that age alone should
      not be considered a contraindication for hepatectomy.

PMID- 23959340
TI  - The influence of parathyroidectomy on restless legs syndrome in patients with
      renal hyperparathyroidism.
AB  - BACKGROUND: Restless legs syndrome (RLS) is a common and poorly understood
      movement disorder that leads to unpleasant leg sensations. Although RLS can be
      idiopathic, secondary etiologies such as iron deficiency and renal failure are
      common. The aim of this prospective cohort study was to evaluate whether RLS is a
      common feature in patients undergoing parathyroidectomy for renal
      hyperparathyroidism (rHPT) and if RLS-related symptoms can be influenced by
      surgery. METHODS: After providing written consent, patients who underwent a
      parathyroidectomy for rHPT between January and November 2011 answered a validated
      RLS-screening-questionnaire (RLSSQ). If this was suggestive for RLS a confirming
      questionnaire (IRLS) was also completed on the day before surgery, on the fifth
      postoperative day, and again during follow-up (minimum 12 months). Perioperative
      parathyroid hormone and calcium levels, as well as the scores of the
      questionnaires were analyzed. RESULTS: Twenty-one patients (14 men, 7 women) with
      a mean age of 47.8 +/- 3.2 years underwent total parathyroidectomy with bilateral
      cervical thymectomy and parathyroid autotransplantation for rHPT. The mean score
      of the RLSSQ of all 21 patients prior to operation was 6.1 +/- 0.5. In 10 of 21
      patients (47.6 %) the results of the RLSSQ were suggestive for RLS with a mean
      score of 8.0 +/- 0.3. The consecutive scores of the IRLS in these latter patients
      significantly dropped from 26.6 +/- 1.4 to 19.0 +/- 2.2 between the preoperative
      and postoperative settings (p < 0.05). After a mean follow-up of 17.3 +/- 3.7
      months the mean scores of the RLSSQ and the IRLS were 6.1 +/- 0.6 and 16.3 +/-
      1.8. CONCLUSIONS: rHPT may play a major role in the severity of RLS-associated
      symptoms in patients with renal failure. Consequently, parathyroidectomy may
      prove to be a valuable tool to reduce RLS-associated morbidity in affected
      patients. However, larger prospective trials are required to confirm the possible
      relation between RLS and rHPT seen in the present study

PMID- 23959341
TI  - Role of cholecystectomy and lymph node dissection in patients with T2 gallbladder
      cancer.
AB  - BACKGROUND: Incidental findings of gallbladder cancer (GBCA) have dramatically
      increased as an initial presentation of the disease because of the expansion of
      laparoscopic cholecystectomy. However, the optimal management of T2 GBCA remains
      at issue. METHODS: We compared our 10-year experience with the consensus surgical
      strategy for T2 GBCA. Between January 2000 and December 2009, 70 patients at
      Severance Hospital, Yonsei University Health System, Seoul, Korea, underwent
      surgical treatment for GBCA stage T2. The medical records of 70 patients with T2
      GBCA were retrospectively reviewed. RESULTS: Radical cholecystectomy was
      performed on only 32 (45.8 %) patients. In patients with T2 GBCA and positive
      lymph nodes (LN), the overall survival rate between cholecystectomy with LN
      dissection and radical cholecystectomy did not show a significant difference.
      Twenty patients experienced recurrence during the follow-up period. Among the 11
      patients who underwent cholecystectomy with liver resection, only 2 (18.2 %)
      patients had an intrahepatic recurrence. Of the 9 patients who underwent
      cholecystectomy without liver resection, 3 (33.3 %) patients had an intrahepatic
      recurrence. However, recurrences at the gallbladder bed occurred only in one and
      two patients, respectively, and were not significantly different between the two
      groups. CONCLUSIONS: There was a large gap between clinical practice and
      treatment guidelines. Though relatively few patients enrolled in this study
      experienced recurrence, cholecystectomy and LN dissection without liver resection
      showed similar survival and recurrence patterns compared with those of radical
      cholecystectomy. To improve consistency between clinical practice and consensus
      guidelines, the role of limited resection for T2 lesions needs further
      evaluation.

PMID- 23959342
TI  - Seaweeds as potential therapeutic interventions for the metabolic syndrome.
AB  - Seaweeds are a characteristic part of the traditional diet in countries such as
      Japan and Korea; these countries also have a lower prevalence of metabolic
      syndrome than countries such as the USA and Australia. This suggests that
      seaweeds may contain compounds that reduce the characteristic signs of obesity,
      diabetes, hypertension, fatty liver and inflammation in the metabolic syndrome.
      Potentially bioactive compounds from seaweeds include polysaccharides, peptides,
      pigments, minerals and omega-3 fatty acids. This review emphasises current
      research on these compounds in isolated cells, animal models and patients. Key
      problems for future research include chemical characterisation of the bioactive
      principles, defining pharmacological responses in all aspects of the metabolic
      syndrome, determining if a therapeutic dose has been administered, and defining
      oral bioavailability of the active ingredients.

PMID- 23959344
TI  - Characterizing spatial structure of sediment E. coli populations to inform
      sampling design.
AB  - Escherichia coli can persist in streambed sediments and influence water quality
      monitoring programs through their resuspension into overlying waters. This study
      examined the spatial patterns in E. coli concentration and population structure
      within streambed morphological features during baseflow and following stormflow
      to inform sampling strategies for representative characterization of E. coli
      populations within a stream reach. E. coli concentrations in bed sediments were
      significantly different (p = 0.002) among monitoring sites during baseflow, and
      significant interactive effects (p = 0.002) occurred among monitoring sites and
      morphological features following stormflow. Least absolute shrinkage and
      selection operator (LASSO) regression revealed that water velocity and effective
      particle size (D 10) explained E. coli concentration during baseflow, whereas
      sediment organic carbon, water velocity and median particle diameter (D 50) were
      important explanatory variables following stormflow. Principle Coordinate
      Analysis illustrated the site-scale differences in sediment E. coli populations
      between disconnected stream segments. Also, E. coli populations were similar
      among depositional features within a reach, but differed in relation to high
      velocity features (e.g., riffles). Canonical correspondence analysis resolved
      that E. coli population structure was primarily explained by spatial (26.9-31.7
      %) over environmental variables (9.2-13.1 %). Spatial autocorrelation existed
      among monitoring sites and morphological features for both sampling events, and
      gradients in mean particle diameter and water velocity influenced E. coli
      population structure for the baseflow and stormflow sampling events,
      respectively. Representative characterization of streambed E. coli requires
      sampling of depositional and high velocity environments to accommodate strain
      selectivity among these features owing to sediment and water velocity
      heterogeneity.

PMID- 23959345
TI  - The effect of management systems and ecosystem types on bark regeneration in
      Himatanthus drasticus (Apocynaceae): recommendations for sustainable harvesting.
AB  - Bark and exudates are widely commercialized non-timber forest products. However,
      the ecological impacts of the harvesting of these products have seldom been
      studied. The aim of this study is to investigate the relationship of tree
      resilience to harvesting intensity in Himatanthus drasticus, a tree that is
      highly exploited in the Brazilian savanna (Cerrado) for its medicinal latex.
      Although the traded product is the latex, the traditional harvesting systems
      involve the removal of the bark of the trees to allow exploitation. A 3-year
      experiment was conducted in two different Cerrado ecosystems (open savanna and
      savanna woodland). Trees were debarked at four debarking intensities to simulate
      the effects of traditional management systems. Measurements of bark growth were
      taken every 6 months, and quantitative and qualitative indexes of bark
      regeneration were obtained. The mortality of the debarked trees was low and could
      not be related to the intensity of harvesting. No signs of attack by fungi or
      insects were recorded. Compared with other species exploited for bark, H.
      drasticus is very resilient to harvesting; however, bark regeneration is
      relatively slow. In both analyzed ecosystems, the regeneration indexes showed
      higher values in the controls than in the treatments, indicating that 3 years is
      not sufficient for total recovery of the rhytidome. Bark regeneration occurred
      primarily by sheet growth and was more rapid in open savanna than in savanna
      woodland. No differences in the rate of bark recovery were found among management
      treatments. Based on the results, sustainable harvesting guidelines are suggested
      for the species.

PMID- 23959343
TI  - Insulin and glucagon signaling in the central nervous system.
AB  - The prevalence of the obesity and diabetes epidemic has triggered tremendous
      research investigating the role of the central nervous system (CNS) in the
      regulation of food intake, body weight gain and glucose homeostasis. This invited
      review focuses on the role of two pancreatic hormones--insulin and glucagon--that
      trigger signaling pathways in the brain to regulate energy and glucose
      homeostasis. Unlike in the periphery, insulin and glucagon signaling in the CNS
      does not seem to have opposing metabolic effects, as both hormones exert a
      suppressive effect on food intake and weight gain. They signal through different
      pathways and alter different neuronal populations suggesting a complementary
      action of the two hormones in regulating feeding behavior. Similar to its
      systemic effect, insulin signaling in the brain lowers glucose production.
      However, the ability of glucagon signaling in the brain to regulate glucose
      production remains unknown. Future studies that aim to dissect insulin and
      glucagon signaling in the CNS that regulate energy and glucose homeostasis could
      unveil novel signaling molecules to lower body weight and glucose levels in
      obesity and diabetes.

PMID- 23959346
TI  - Determination of antimicrobial and heavy metal resistance profiles of some
      bacteria isolated from aquatic amphibian and reptile species.
AB  - The aim of the present study was to determine the level of antibiotic resistance
      patterns and distribution of heavy metal resistance of bacterial isolates from
      aquatic animals (Lissotriton vulgaris, Pelophylax ridibundus, Emys orbicularis,
      Mauremys rivulata, and Natrix natrix) in Turkey (Kavak Delta). A total of 153
      bacteria have been successfully isolated from cloaca and oral samples of the
      aquatic amphibians and reptilians which were found, namely, Aeromonas sp. (n =
      29), Plesiomonas sp. (n = 7), Vibrio sp. (n = 12), Citrobacter sp. (n = 12),
      Enterobacter sp. (n = 11), Escherichia sp. (n = 22), Klebsiella sp. (n = 22),
      Edwardsiella sp. (n = 6), Hafnia sp. (n = 1), Proteus sp. (n = 19), Providencia
      sp. (n = 8), and Pseudomonas sp. (n = 4). In terms of antibiotic and heavy metal
      susceptibility testing, each isolate was tested against 12 antibiotics and 4
      metals. There was a high incidence of resistance to cefoxitin (46.40 %),
      ampicillin (44.44 %), erythromycin (35.29 %), and a low incidence of resistance
      to gentamicin (6.53 %), kanamycin (8.49 %), chloramphenicol (9.15 %), and
      cefotaxime (10.45 %). The multiple antibiotic resistance index of each bacterial
      species indicated that bacteria from raised amphibians and reptiles have been
      exposed to tested antibiotics, with results ranging from 0 to 0.58. Most isolates
      showed tolerance to different concentrations of heavy metals, and minimal
      inhibition concentrations ranged from100 to >3,200 MUg/mL. According to these
      results, a significant occurrence of bacteria in the internal organs of reptiles
      and amphibians, with a high incidence of resistance against antibiotics and heavy
      metals, may risk aquatic animals and the public health. These data appoint the
      importance of epidemiological surveillance and microbiological monitoring and
      reinforce the need to implement environment protection programs for amphibian and
      reptile species.

PMID- 23959347
TI  - Selenium levels in neoplastic breast lesions.
AB  - AIMS AND OBJECTIVES: The aim of this prospective case controlled study was to
      evaluate the tissue levels of selenium in patients with cases of fibroadenoma,
      cancer of the breast and in the controls in order to relate them to the
      occurrence of breast diseases. SUBJECTS AND METHODS: Consecutive consenting
      patients who had histologically confirmed breast cancer and fibroadenoma
      attending the General surgical outpatients departments of Obafemi Awolowo
      University Teaching Hospital Complex, Ile-Ife, were recruited for the study. One
      gram of core disease breast tissues was taken for Selenium level estimation.
      RESULTS: There were 127 female subjects;. 95 (74.8%) cases of fibroadenoma and 32
      (25.2%) of breast cancer. While breast cancer was common on the left,
      fibroadenoma was more common on the right breast (? = 8.994; p=0.011). The median
      tissue level of selenium in patients with fibroadenoma was 0.0272 mg/g with a
      range of 0.0124 to 0.0576 mg/g and that of the cancer patients was 0.0178 mg/g
      with a range 0.0072 to 0.0436 mg/g. These were statistically significantly
      different ( p=0.001). Factors affecting tissue selenium level include age
      (p<0.001), overall stage of breast cancer (p<0.001), maximum length of breast
      mass (p=0.023), previous delivery (p=0.004), age at last confinement (p=0.007),
      parity (p<0.001), oestrogen receptor (ER) status (p<0.001) and progesterone
      receptor (PR) status (p=0.021). CONCLUSION: Tissue selenium was lower in breast
      cancer than in fibroadenoma; Tissue selenium inhibits carcinogenesis; low tissue
      level of selenium therefore may be a factor in the development of breast cancer.

PMID- 23959348
TI  - Blindness and visual impairment in north central Nigeria: a hospital based study.
AB  - AIMS AND OBJECTIVES: To determine the pattern of visual impairment and blindness
      in patients seen at a hospital in North Central Nigeria. PATIENTS AND METHODS:
      All new eye patients seen at Adoose Specialist Hospital, Jos, North Central
      Nigeria with conditions potentially leading to blindness and visual impairment
      over a ten year period were studied.The patients' demographic information,
      diagnosis and visual acuity were retrieved from the records. RESULTS: A total of
      2536 patients were reviewed. There were 1315 (51.9%) males. Bilateral blindness
      was seen in 279 (11.0%) of the patients. Visual impairment was seen in 745
      (29.4%) patients. Severe visual impairment (SVI) was seen in 4(0.2%), moderate
      (MoVI) in 225 (8.9%) and mild (MVI) in 237(9.3%). Blindness and visual impairment
      increased significantly with age. Blindness was most prevalent among the farmers
      (40.2%), followed by the house wives (24.4%). It was attributable to refractive
      error in 33.3%, cataract in 28.3%, glaucoma in 13.3%, posterior segment disease
      in 8.2%, glaucoma/cataract in 7.9%, cataract/posterior segment disease in 1.8%,
      trauma and uveitis each in 1.4%, with other ocular conditions (affecting the
      globe) seen in 1.1% and corneal disorders in 0.7%. Proportionately more males had
      glaucoma, trauma, corneal disorders and posterior segment disease, while females
      predominated with refractive error, conjunctivitis and cataract. CONCLUSIONS:
      Refractive error, cataract and glaucoma were the major causes of blindness,
      underpinning the significance of these conditions in ocular morbidity.

PMID- 23959349
TI  - Physical activity profile of senior civil servants in Lagos, Nigeria: need for
      effective strategies for improvement.
AB  - AIMS AND OBJECTIVES: To investigate the profile of physical activity (PA) among
      Lagos State senior civil servants (LSCSs). SUBJECTS AND METHODS: A cross
      sectional survey in which 305 LSCSs (163 men, 142 women) with age range 25 65
      years, in five ministries of the LSCS was carried out in May of 2011. The Global
      Physical Activity Questionnaire (GPAQ) was used to assess respondents' PA at
      work, for transport, and during leisure time during the last 7 days. RESULTS:
      Overall, 56.7% of the respondents (58.3% men and 54.9% women) were active;
      equivalent to 43.3% inactive respondents (41.7% men and 54.9% women). In spite of
      the high prevalence of physical inactivity in the women, gender was not
      significantly associated with PA levels (p = 0.718). However, the educational
      status and cadre of respondents were significantly associated with PA levels (p <
      0.05). CONCLUSION: The findings of this study showed that close to half of LSCSs
      were physically inactive. There was no significant difference between the PA
      levels of men and women but educational status and cadre were associated with the
      PA levels of respondents. The results provided by this study suggests the need
      for the Lagos State government and stakeholders to formulate polices, plan
      programmes and interventions for LSCSs to get more physically active.

PMID- 23959350
TI  - Clinical presentation of oral squamous cell carcinoma.
AB  - AIMS AND OBJECTIVES: This study aims to present the symptoms first observed by
      patients diagnosed of oral squamous cell carcinoma (OSCC) presenting at the
      University College Hospital, Ibadan between January 1990 and December 2008 as
      well as the time lag between the observation and presentation in the hospital.
      PATIENTS AND METHODS: This is a retrospective review of patients that have been
      diagnosed histologically as squamous cell carcinoma of the oral cavity at the
      University College Hospital Ibadan, Nigeria between January 1990 and December
      2008. RESULTS: Painful tooth/teeth which are not mobile were the most common
      symptom in these patients (27.5%). However, about 59.4% of patients had painless
      symptoms at the onset of the disease. The interval between onset of symptoms and
      clinical presentation ranged from 3 weeks to 36 months with a mean duration of 7
      +/- 6.3 months. Paradoxically, patients that experienced painful symptoms at the
      onset of disease presented later than those who had painless symptoms CONCLUSION:
      The first symptoms observed by these patients were not pathognomonic of oral
      cancer but are shared by several relatively more common oral diseases. Awareness
      of the populace about oral cancer should be increased as well as the index of
      suspicion of the medical practitioner for OSCC.

PMID- 23959351
TI  - Managing glaucoma in Lagos State, Nigeria - availability of Human resources and
      equipment.
AB  - AIMS AND OBJECTIVES: There is a paucity of data onthe human resourcesand
      ophthalmic equipmentavailable for the diagnosis and management of glaucoma in
      Nigeria. This study is aimed at describing the ophthalmic human resources, as
      well as available and functioning equipment used in diagnosing and managing
      glaucoma in Lagos State, Nigeria. MATERIALS AND METHODS: This was a prospective
      multicentre cross sectional study.Data on human resources and equipmentavailable
      were collected from all government tertiaryand secondary health institutions in
      the state. One large-practice private eye hospital in the state was included for
      comparative purposes. RESULTS: The average number of ophthalmologists per
      hospital was 1.3 and 4.5 in the secondary and tertiary centres respectively, with
      overall ophthalmologists to population ratio of 1:400,000, and ophthalmic nurses
      to population ratio of 1:150,000. There were only 2 full time low vision
      therapists and 3 equipment technicians. Only the private hospital had a dedicated
      patient counsellor and an eye unit manager. 64% of ophthalmic equipment in the
      government sector were functioning compared with 100% in the private centre.
      Overall, equipment to population ratios were; slit lamp=1:517,000, 78/90D
      lens=1:1,487,000, tonometer=1:660,000, visual field analyser=1:2,380,000, and
      pachymeter=1:5,950,000. CONCLUSIONS: Current population ratios for
      ophthalmologists and ophthalmic nurses in the state meets vision 2020
      recommendations, but there are shortages of other key human resources such as
      equipment technicians, low vision therapists and patient counsellors. In
      addition, equipment required for the management of glaucoma wereinadequate, not
      available or not functioning. Findings from this study suggest that there is an
      urgent need for increased government funding to glaucoma services in Lagos State.

PMID- 23959352
TI  - Pistol-grip Syringe holder (Cameco syringe pistol) in fine needle aspiration
      Biopsy: any advantages over the use of direct finger grip?
AB  - AIMS AND OBJECTIVES: The study seeks to determine the advantages of using the
      pistol-grip syringe holder in the performance of FNAB over the use of direct
      finger grip method. PATIENTS AND METHODS: The skin is cleaned with gauze soaked
      in methylated spirit and the lump is located and firmly held between the thumb
      and fore finger of the free hand. The syringe is held by the out side of the
      barrel or by pistol-grip, and the needle tip pushed into the lesion. The plunger
      is partially retracted, creating a negative pressure. The cutting edge of the
      needle tip frees the cells inside the lesion which are sucked into the fine bore
      of the needle. The contents of the needle are then emptied on a microscopic slide
      and thinly smeared. The slides are then fixed in alcohol and later stained. These
      were examined under the microscope and a comparison between the aspirations using
      pistol-grip and direct finger grip was made. RESULTS: A total of 266 cases of
      FNABs were carried out from 1st January to 31st December, 2008. There were 89
      breast cases out of which 42 (47%) had pistol-grip method and 47 (53%) had direct
      finger grip method; 74 thyroid cases out of which 28 (38%) were pistol-grip and
      46 (62%) were direct finger grip cases; 56 cases of lymph node FNABs of which
      18(32%) and 38 (68%) had pistol-grip and direct finger grip methods respectively.
      There were 23 cases of salivary gland FNABs having 8 (35%) and 15 (65%) as pistol
      grip and direct finger grip methods respectively. Marked cellularity was observed
      in the majority of cases using both methods of FNABs. CONCLUSION: This study has
      shown that the use of pistol-grip syringe holder in the performance of FNABs has
      no significant advantage compared to the direct finger grip method.

PMID- 23959353
TI  - Pattern of paediatric solid cancers seen in radiotherapy and oncology department,
      Ahmadu Bello University Teaching Hospital, Zaria - Nigeria.
AB  - Summary AIMS AND OBJECTIVES: To evaluate the Pattern of Paediatric solid cancers
      seen over 5 years in the Radiotherapy and Oncology Department of Ahmadu Bello
      University Teaching Hospital, Zaria-Nigeria. MATERIALS AND METHODS: The study
      involved patients aged 16 years and below diagnosed with solid cancers referred
      to the Radiotherapy and Oncology Centre for further management. Between January
      2006 and December 2010, a total of 136 new patients with paediatric solid cancers
      were seen and evaluated. Only patients with histological confirmation were
      included in the study (136 out of 141 patients) irrespective of cancer type, sex,
      co-morbidity and performance status. Patients' folders were reviewed
      retrospectively with a structured pro forma. Information retrieved from patients
      folder included age, sex, histological type, stage and types of treatments
      received. Results were presented in tables. RESULTS: A total of 136 patients were
      evaluated with a mean age of 6.9 years (median of 5 years, age range 1.5 - 16
      years). 74 patients (54.4%) were 5 years and below and 98 patients (72%) were 10
      years and below. The sex ratio M:F was 1.3:1. At presentation at the Radiotherapy
      and Oncology centre, only 4 (3%) patients had early stage disease, 100 (73.5%)
      with locally advanced disease and 32 (23.5%) with metastatic disease.
      Retinoblastoma 48 (35.3%) was the commonest cancer seen followed by soft tissue
      sarcoma 20 (14.7%, all rhabdomyosarcoma), lymphomas 15 (11%) (9 Burkitt's and 6
      Hodgkin's lymphoma), nephroblastoma 13 (9.6%), bone sarcoma 12 (8.8%) (8
      Osteosarcoma and 4 Ewing's sarcoma), nasopharyngeal cancers 8 (5.9%), brain
      cancer 6 (4.4%), sacrococcygeal tumours 6 (4.4%) and other cancers accounted for
      8 (5.9%). 116 (85.3%) patients received chemotherapy, 86 (63.2%) patients were
      scheduled for radiotherapy but only 21 (15.4%) received local field irradiation
      due to financial constraints and 43 (31.6%) had definitive surgery. Palliative
      care with medications was done in 22 (16.2%) patients. Of 48 patients with
      retinoblastoma, 30 affected left eye, 16 affected right eye and 2 patients were
      with bilateral retinoblastoma. The mean age for retinoblastoma was 3.8 years
      (median age of 3 years and mode is 3 years). The mean age for rhabdomyosarcoma
      was 8.7 yr (median age of 6.5 years). CONCLUSION: Paediatric solid cancers were
      found to be more common in males than females with more than half being diagnosed
      in children aged 5 years and below. Retinoblastoma and rhabdomyosarcoma were the
      most common neoplasms. Most patients presented with locally advanced and
      metastatic cancers. Geographic variation exists with histological types.

PMID- 23959354
TI  - Tuberculosis treatment outcome and its determinants in a tertiary care setting in
      south-eastern Nigeria.
AB  - AIMS AND OBJECTIVES: To evaluate tuberculosis treatment outcomes in a Nigerian
      tertiary-care setting and to identify factors associated with unsuccessful
      treatment outcome. PATIENTS AND METHODS: Retrospective audit of tuberculosis
      patients registered for treatment from January 2006 to December 2010 at Federal
      Medical Centre Abakaliki, Nigeria. Six treatment outcome criteria were assessed
      based on guidelines set by the World Health Organisation (WHO). Analysis was
      conducted using SPSS. Multivariable logistic regression analysis were used to
      identify independent predictors for unsuccessful treatment outcome and
      statistical significance was taken as P <0.05. RESULTS: A total of 671 patients
      (55% male, 45% female) with a mean age of 36.4 years were registered for
      treatment; 147 (22%) were smear-positive, 270 (40%) smear-negative and 254 (38%)
      had extra-pulmonary tuberculosis. Also, 189 (28.2%) of them were HIV positive
      and; 341 (51%) lived in a rural area. Overall, 387 patients (57.7%) had a
      successful treatment outcome and 284 (42.3%) had an unsuccessful treatment
      outcome. Of the patients with unsuccessful treatment outcome, 192 (67.6%) had
      defaulted, 55 (19.4%) had died, 3 (1%) had treatment failure and 34 (12%) were
      transferred-out. Nil significant change in trend of treatment success over the
      study period [P = 0.75 for trend]. In multivariable analysis, unsuccessful
      treatment was associated with older age (aOR = 2.3), rural residence (aOR = 2.1),
      smear negative PTB (aOR=1.6), being on retreatment (aOR 3.8), and HIV
      seropositivity (aOR=1.7). CONCLUSION: Treatment success rate was poor; targeted
      measures should be considered to improve treatment success among identified high
      risk groups.

PMID- 23959355
TI  - Prevalence of erectile dysfunction (ED) and its risk factors among adult men in a
      Nigerian community.
AB  - AIMS AND OBJECTIVES: This study assesses the prevalence of erectile dysfunction
      as well as its risk factors. MATERIALS AND METHODS: This is a descriptive cross
      sectional study among 650 adult males, aged between 18 and 70 years selected by
      multi-stage sampling technique. Data were obtained from respondents selected from
      4 wards in Olorunda local government area of Osogbo in Osun state, Southwest,
      Nigeria, using pre-tested semi-structured questionnaires. RESULTS: Majority of
      the respondents were between ages 20-29 years with mean age of 33.6 +/- 13.4
      years. Most of the respondents [547(91.2%)] were aware of ED and 63.4% of them
      said it can be treated. The prevalence of ED was 43.8% and factors such as
      increasing age (p=0.00), hypertension (p=0.000), diabetes mellitus (p=0.000),
      perineal surgery (p=0.000), alcohol consumption (p=0.000), and smoking (p=0.000)
      were found to be significantly associated with developing ED. CONCLUSION AND
      RECOMMENDATION: The level of awareness about erectile dysfunction was high among
      respondents and the prevalence from this study was 43.8%. Factors associated with
      ED from this study included increasing age, alcohol consumption, hypertension,
      perineal injury and surgery. Hence, the risk of developing ED can be
      significantly reduced by educating men about life style modifications such as
      reduction in alcohol intake and smoking, as well as regular exercises.

PMID- 23959356
TI  - Socio demographic and clinical correlates of knee pain in adult women attending a
      primary care clinic.
AB  - AIMS AND OBJECTIVES: The objectives of the study were to determine the socio
      demographic and clinical correlates of knee pain in women in a primary care
      clinic. PATIENTS AND METHODS: The study was a cross-sectional survey of 400 women
      attending the General Outpatients' clinic of the University College Hospital
      (U.C.H.), Ibadan, Nigeria using the systematic random sampling technique.
      RESULTS: The prevalence of knee pain was 42.0% (95% CI 40.0- 41.0). The
      radiographic findings in the knees showed mostly osteophytes in 24 out of the
      28(85.7%) respondents who had radiographs done. The highest prevalence of knee
      pain was found in caterers and traders, 62.5% and 51.6%, respectively (p= 0.001).
      Multivariate analysis done using logistic regression with a backward selection
      showed that the odds of developing knee pain increases with age (Odds
      Ratio=1.585, 95% CI 1.321-1.903, p=0.000), and body mass index (Odds Ratio 1.587,
      95% CI 1.295-1.946, p=0.000). CONCLUSION: The prevalence of knee pain in women
      seen at the primary care clinic is high. Preventive measures for knee pain need
      to be instituted.

PMID- 23959357
TI  - Urological manifestations and management of human immuno-deficiency virus
      infection a review.
AB  - The human immunodeficiency virus (HIV) infection has become a pandemic with more
      than 40 million infected people worldwide. The virus attacks the immune system of
      the host thus exposing them to opportunistic infections in various systems of the
      body. The use of highly active anti-retroviral therapy (HAART) has converted a
      previously lethal condition to a chronic condition with relatively benign cause.
      This has allowed infected patients to live longer than before. Though beneficial,
      however, this has been associated with increased incidence of complications seen
      in these patients involving many systems. Urogenital system is not an exception
      to this and indeed is a common site for these complications. Urological symptoms
      or signs are often seen in HIV patients and sometimes appear as the first
      indicator of the disease. These manifestations can be benign or malignant,
      infective or non-infective, disease or drug-related. Their appearance may also be
      a pointer to the deterioration of the infection into a full blown AIDS. It is
      therefore important that every doctor has a good knowledge of the possible
      urological manifestations of the disease. Early recognition and prompt treatment
      of these complications may be of prognostic significance as they may produce
      significant morbidity and mortality if left untreated. This article highlights
      the clinical features and management of common urological manifestations of HIV. 

PMID- 23959358
TI  - Reducing maternal mortality in Nigeria: the need for urgent changes in financing
      for maternal health in the Nigerian health system.
AB  - AIMS AND OBJECTIVES: Nigeria's maternal mortality indices are among the worst in
      the world. Various approaches aimed at combatting the persistently high maternal
      mortality rates in the past have been ineffective. The objective of this article
      was to evaluate the fairness and equitability of financing for maternal health in
      the Nigerian health system. METHODS: A review of the performance of the Nigerian
      Health system with regards to financing for maternal healthcare and comparison
      with other health systems utilising internationally accepted criteria was done.
      RESULTS: Household out-of -pocket payment was found to be the largest source of
      health care financing in the Nigerian health system contributing as much as 65.6
      % of total health expenditure. This is in sharp contrast to the performance of
      more effective health systems like that in South Africa where health care is free
      for pregnant and breast feeding mothers. The result is that South Africa reports
      less than a tenth of total maternal mortalities reported from Nigeria annually.
      The current Nigeria health financing system is not equitable and appears to
      encourage maternal mortalities since it does not cater for the most vulnerable.
      CONCLUSION: There is an urgent need for a review of financing of maternal health
      in Nigeria to achieve universal access to maternal health care. An urgent
      overhaul of the currently under performing National Health Insurance scheme or
      adoption of the simpler system based on funding from taxation with universal
      access for health care including maternal care and services free at the point of
      access is suggested.

PMID- 23959359
TI  - Cortical blindness in obstetric patients: case report of two different
      presentations.
AB  - Cortical blindness can complicate pre-eclampsia/eclampsia. This normally resolves
      between a few hours and days with full restoration of patients sight. In this
      case report, we present the clinical course of two women in whom eclampsia was
      further complicated with blindness. One had pre-partum blindness which resolved
      after few hours while the second developed post-partum blindness that occurred
      after an episode of ischaemic cerebrovascular accident (CVA) and it became
      persistent. The patients were managed by standard pre-eclampsia/ eclampsia
      regimen; these entail the use of intravenous magnesium sulphate, i/v hydralazine
      and fluid restriction, as well as expedite delivery. Diagnosis was further
      confirmed by computed tomography (CT) that demonstrated low density areas
      localised predominantly in the occipital areas. 

PMID- 23959360
TI  - Deep calf cavernous haemangioma in a 10 year- old girl: a case report.
AB  - Haemangiomas are abnormal proliferation of blood vessels in any vascularised
      tissue. They can be capillary or cavernous varieties. Cavernous are either of
      cutaneous or deep types. Cavernous when compared with the capillary haemangioma
      is rare. Rarer still is the deep type of cavernous haemangioma. This is a report
      of a 10 year old Nigerian girl who presented with a right posterior leg swelling
      of 8 year duration, size initially was that of a peanut but increased to fill the
      entire calf region causing pain to the patient as well as cosmetic and anxiety
      concern to the parents. No preceding history of trauma, no associated systematic
      symptoms. She had exploratory laparatomy at 1 year of age at a private hospital
      for an abdominal mass which was excised. Pre-operative plain radiograph, Magnetic
      Resonance Imaging(MRI), Abdominopelvic ultrasound scan (USS) were done, fine
      needle aspiration cytology (FNAC) though done was not helpful. Histo-pathology
      result of excised leg mass confirmed diagnosis; there was a free margin of
      excision. Post-operatively, clinical improvement was marked. 

PMID- 23959361
TI  - Utero-peritoneal fistula, a rare complication of laparoscopic myomectomy scar
      dehiscence: a case Report.
AB  - OBJECTIVE: The objective is to report a case of utero-peritoneal fistula caused
      by laparoscopic myomectomy dehiscence, diagnosed by colour Doppler ultrasound
      scan and confirmed by x-ray HSG and MRI. The aim of our report lies on the
      importance of imaging in the diagnosis of fistulous processes involving the
      uterus. CASE REPORT: A 36 year old woman (G6,P0)presented with intense
      dysmenorrheal and intermenstrual spotting since laparoscopic myomectomy 2 years
      before. A laparoscopic myomectomy dehiscence with utero-peritoneal fistula was
      diagnosed by pelvic ultrasound, hysterosalpingogram (HSG) and magnetic resonance
      imaging (MRI).

PMID- 23959362
TI  - Genetics: new HLA variants could predict T1DM risk in African Americans.

PMID- 23959363
TI  - Paediatrics: Circulating microRNAs-predictors of obesity?

PMID- 23959364
TI  - Diabetes: the search for mechanisms underlying bariatric surgery.

PMID- 23959367
TI  - Cancer: ADT and acute kidney injury-causal or casual relationship?
AB  - A recent observational study has reported that androgen deprivation therapy for
      prostate cancer is associated with an increased risk of acute kidney injury. As a
      result of limited biological plausibility and critical measured and unmeasured
      confounders, the reported link is more likely to be casual than causal.

PMID- 23959365
TI  - Clinical implications of shared genetics and pathogenesis in autoimmune diseases.
AB  - Many endocrine diseases, including type 1 diabetes mellitus, Graves disease,
      Addison disease and Hashimoto disease, originate as an autoimmune reaction that
      affects disease-specific target organs. These autoimmune diseases are
      characterized by the development of specific autoantibodies and by the presence
      of autoreactive T cells. They are caused by a complex genetic predisposition that
      is attributable to multiple genetic variants, each with a moderate-to-low effect
      size. Most of the genetic variants associated with a particular autoimmune
      endocrine disease are shared between other systemic and organ-specific autoimmune
      and inflammatory diseases, such as rheumatoid arthritis, coeliac disease,
      systemic lupus erythematosus and psoriasis. Here, we review the shared and
      specific genetic background of autoimmune diseases, summarize their treatment
      options and discuss how identifying the genetic and environmental factors that
      predispose patients to an autoimmune disease can help in the diagnosis and
      monitoring of patients, as well as the design of new treatments. 

PMID- 23959368
TI  - Reproductive endocrinology: maternal cholestasis and offspring metabolic
      abnormalities.
AB  - Papacleovoulou and colleagues demonstrate that maternal cholestasis during
      pregnancy is associated with offspring adiposity and metabolic abnormalities,
      both in humans and in mice. This study reinforces the overwhelming evidence of
      the critical role of the in utero environment as a major determinant of adult
      health and disease.

PMID- 23959366
TI  - The role of FOXO1 in beta-cell failure and type 2 diabetes mellitus.
AB  - Over the past two decades, insulin resistance has been considered essential to
      the aetiology of type 2 diabetes mellitus (T2DM). However, insulin resistance
      does not lead to T2DM unless it is accompanied by pancreatic beta-cell
      dysfunction, because healthy beta cells can compensate for insulin resistance by
      increasing in number and functional output. Furthermore, beta-cell mass is
      decreased in patients with diabetes mellitus, suggesting a primary role for beta
      cell dysfunction in the pathogenesis of T2DM. The dysfunction of beta cells can
      develop through various mechanisms, including oxidative, endoplasmic reticulum or
      hypoxic stress, as well as via induction of cytokines; these processes lead to
      apoptosis, uncontrolled autophagy and failure to proliferate.
      Transdifferentiation between beta cells and alpha cells occurs under certain
      pathological conditions, and emerging evidence suggests that beta-cell
      dedifferentiation or transdifferentiation might account for the reduction in beta
      cell mass observed in patients with severe T2DM. FOXO1, a key transcription
      factor in insulin signalling, is implicated in these mechanisms. This Review
      discusses advances in our understanding of the contribution of FOXO1 signalling
      to the development of beta-cell failure in T2DM. 

PMID- 23959369
TI  - Vitamin D and human health: more than just bone.

PMID- 23959370
TI  - Plant metallomics.

PMID- 23959371
TI  - Assessing the guest-accessible volume in MOFs using two-photon fluorescence
      microscopy.
AB  - The assessment of guest-accessible volume in MOFs can be reliably done by using
      two-photon confocal fluorescence microscopy (TPM) with a tool-box of dyes with a
      wide range of sizes. It would be applicable to any porous materials, whose single
      crystal structures are not available, or non-crystalline materials. 

PMID- 23959372
TI  - Eco-friendly fabrication of hydrophilic ZSM-5 membranes for alcohol upgrading.
AB  - The synthesis of continuous and low-siliceous ZSM-5 membranes was achieved
      without organic templates under mild conditions (a low temperature of 100 
      degrees C and ambient pressure). The resultant high-quality membranes with good
      water perm-selectivity were further applied in water-alcohol separation,
      exhibiting an extraordinarily high separation factor of above 10,000 and an
      improved water flux (3.43-6.88 kg m(-2) h(-1)) for ethanol and isopropanol
      aqueous azeotropes.

PMID- 23959373
TI  - Liver metastasis of extremity pleomorphic liposarcoma treated with hepatic
      resection.

PMID- 23959374
TI  - Runt-related transcription factor 3: single nucleotide polymorphism rs760805,
      gene expression, and methylation status in Helicobacter pylori -infected patients
      for determination of gastric cancer risk.
AB  - PURPOSE: Repression of Runt-related transcription factor 3 (Runx3) gene, a tumor
      suppressor, has been known to be involved in Helicobacter pylori (H. pylori)
      associated gastric carcinogenesis and cancer development. The present study was
      undertaken to study the Runx3 intronic T/A polymorphism (rs760805) in H. pylori
      infected patients and uninfected controls of Tamil Nadu region, South India.
      Also, Runx3 gene expression, HK alpha (H,K-ATPase) gene expression and the
      methylation status of the Runx3 CpG island was determined. METHODS: In a
      prospective study, tissue biopsies were collected from 40 H. pylori-infected
      patients and 40 infection negative controls. Single nucleotide polymorphism
      analysis was carried out by polymerase chain reaction (PCR)-single-strand
      conformational polymorphism, and DNA sequencing. Gene expression analysis of
      Runx3 and HK alpha was carried out using semiquantitative reverse transcriptase
      PCR. Methylation analysis of Runx3 CpG island was undertaken using
      methylationspecific restriction digestion-PCR. RESULTS: The homozygous TT
      genotype was found to be the predominant genotype in positive samples and
      negative controls. No significant variation in gene expression was observed in
      positive samples and controls with respect to Runx3 and Hk alpha genes.
      Methylation analysis suggested that there was a lack of methylation except in a
      few subjects studied. CONCLUSION: The present study, first from this region,
      could neither detect significant repression of the Runx3 and HK alpha genes nor
      methylation in positive patients studied suggesting a lack of involvement of this
      tumor suppressor as a risk factor in the H. pylori-associated gastric
      carcinogenesis in the South Indian population studied.

PMID- 23959375
TI  - GnpIS: an information system to integrate genetic and genomic data from plants
      and fungi.
AB  - Data integration is a key challenge for modern bioinformatics. It aims to provide
      biologists with tools to explore relevant data produced by different studies.
      Large-scale international projects can generate lots of heterogeneous and
      unrelated data. The challenge is to integrate this information with other
      publicly available data. Nucleotide sequencing throughput has been improved with
      new technologies; this increases the need for powerful information systems able
      to store, manage and explore data. GnpIS is a multispecies integrative
      information system dedicated to plant and fungi pests. It bridges genetic and
      genomic data, allowing researchers access to both genetic information (e.g.
      genetic maps, quantitative trait loci, markers, single nucleotide polymorphisms,
      germplasms and genotypes) and genomic data (e.g. genomic sequences, physical
      maps, genome annotation and expression data) for species of agronomical interest.
      GnpIS is used by both large international projects and plant science departments
      at the French National Institute for Agricultural Research. Here, we illustrate
      its use. Database URL: http://urgi.versailles.inra.fr/gnpis. 

PMID- 23959376
TI  - Effectiveness of a desensitizing agent before in-office tooth bleaching in
      restored teeth.
AB  - OBJECTIVES: The aim of this clinical trial was to evaluate the effectiveness and
      tooth sensitivity associated with bleaching in patients with composite
      restorations in anterior teeth after the application of a desensitizing agent.
      MATERIAL AND METHODS: Bleaching was performed with 35 % hydrogen peroxide gel in
      30 patients with composite restorations in anterior teeth, divided according to
      the prior application of a desensitizing agent (De), or a placebo (Pl), on
      maxillary superior teeth. Color was recorded at baseline, 1 week after each
      session and 6 months after treatment. The experience of tooth sensitivity (TS)
      was recorded on an NRS (0-4) during bleaching and 24 h after each session.
      Bleaching effectiveness was evaluated by one-way ANOVA and Tukey's tests (alpha =
      0.05). The percentage of TS was evaluated by Fisher's exact test. For each
      treatment, periods were compared using the Wilcoxon signed-rank test (alpha =
      0.05), and at each period, treatments were compared using Mann-Whitney U test.
      RESULTS: Both groups showed similar tooth color enhancement and color stability
      after 6 months (p < 0.05). No significant difference in prevalence of sensitivity
      was detected between groups (p < 0.001). Higher TS intensity (median [first/third
      quartiles]) was observed for Pl (1.5 [1/1.75]) compared with De (0.5 [0/1])
      during treatment (p < 0.05). CONCLUSIONS: The use of a desensitizing gel (5 %
      potassium nitrate, 2 % sodium fluoride) before tooth bleaching in patients with
      composite restorations did not reduce the prevalence of tooth sensitivity, but
      reduced the intensity of TS during bleaching. CLINICAL RELEVANCE: Although the
      use of a desensitizing agent before bleaching, in patients with composite resin
      restorations, did not reduce the prevalence of TS, a reduction of the TS
      intensity during the protocol was observed without jeopardizing the whitening
      outcome.

PMID- 23959377
TI  - Oval-shaped canal retreatment with self-adjusting file: a micro-computed
      tomography study.
AB  - OBJECTIVES: The aim of this study was to assess the efficacy of removing the
      filling material from oval-shaped canals with rotary retreatment files, with or
      without the additional use of self-adjusting file (SAF), using micro-computed
      tomography. MATERIALS AND METHODS: Oval-shaped canals from 20 maxillary premolars
      were prepared and assigned to two groups (n = 10), according to the obturation
      technique: cold lateral condensation (CLC) or vertical condensation (VC). Then,
      retreatment procedure was performed with retreatment rotary instruments followed
      by SAF. The specimens were scanned after each procedure and the volume of the
      filling material calculated. Median and interquartile range (IQR) percentages of
      the remaining filling material after each retreatment technique were
      statistically compared by Wilcoxon and Mann-Whitney U tests with a significance
      level of 5 %. RESULTS: The median percentage volume of the filling residue after
      rotary retreatment procedure was 1.59 (IQR = 1.26) and 0.42 (IQR = 0.86) in the
      CLC and VC groups, respectively (p < 0.05). After the use of SAF, the median
      percentage was 1.26 (IQR = 0.75) and 0.12 (IQR = 0.53) in the CLC and VC groups,
      respectively (p < 0.05). Statistically significant difference was also observed
      within the group after the additional use of SAF (p < 0.05). CONCLUSIONS: None of
      the retreatment procedures completely removed the filling material. The
      additional use of the SAF improved the removal of filling material after the
      retreatment procedure with rotary instruments. CLINICAL RELEVANCE: Filling
      material left after retreatment procedure may harbour necrotic tissue and
      bacteria, which could lead to a persistent disease and reinfection of the root
      canal system. The additional use of self-adjusting file after the conventional
      retreatment procedures may improve root canal cleanliness, allowing a better
      action of the irrigating solution.

PMID- 23959378
TI  - Increased immunoexpression of trefoil factors in salivary gland tumors.
AB  - OBJECTIVE: Very little is known about the role of trefoil factors (TFFs) in
      salivary gland tumors, and TFF immunoexpression has never been investigated in
      such tumors. The aim of this study was to evaluate TFF immunoexpression in benign
      and malignant salivary gland tumors. MATERIALS AND METHODS: Benign (n = 25) and
      malignant (n = 25) salivary gland tumor specimens were included in this study,
      using mucocele (n = 25) specimens as a control group. Immunohistochemical
      staining was performed to evaluate the expression of TFFs (TFF1, TFF2, and TFF3)
      by semiquantitative means. RESULTS: Expression of TFF1, TFF2, and TFF3 was
      significantly increased in benign (p = 0.001, p = 0.005, p < 0.001, respectively)
      and malignant (p < 0.001, p < 0.001, p < 0.001, respectively) groups as compared
      with the control group. Patterns of co-expression between TFF1/TFF2, TFF2/TFF3,
      and TFF1/TFF3 were different among the three groups. CONCLUSIONS: The present
      study provided new information showing that all TFFs were significantly increased
      in benign and malignant salivary gland tumors, and overexpression of TFFs could
      be associated with neoplastic transformation in salivary gland tissues. CLINICAL
      RELEVANCE: Overexpression of TFFs may be useful as biomarkers in terms of
      differential diagnosis between salivary gland tumors and other oral neoplasms for
      which clinical manifestations are indistinguishable.

PMID- 23959379
TI  - Imaging or trusting on surface anatomy? A comparison between fluoroscopic
      guidance and anatomic landmarks for femoral artery access in diagnostic cardiac
      catheterization. A randomized control trial.
AB  - We performed a randomized controlled trial to test the potential benefits of
      fluoroscopic-guided femoral artery puncture. Observational studies showed a
      consistent relationship between common femoral artery (CFA) and the head of
      femur. Fluoroscopy locating the femoral head may increase the accuracy of femoral
      puncture and consequently decrease the vascular complication. Despite these
      theoretical benefits, we have no sufficient evidence to verify its advantages.
      Patients undergoing diagnostic cardiac catheterization were randomized into
      fluoroscopic and anatomic method groups. Of total of 609 patients participated in
      this study, 305 and 304 patients were assigned to fluoroscopic and anatomic
      method groups, respectively. Fluoroscopy significantly increases the puncture
      over the femoral head (96.7 vs. 82.3 %, p value 0.001) and also the fluoroscopic
      method increased CFA puncture significantly (93.8 vs. 87.5 %, p value 0.012). The
      combined end point of "proper" femoral puncture (CFA puncture over the femoral
      head) was highly significant in our fluoroscopy-guided method (91.8 vs. 75.7 %, p
      value <0.0001). Hematoma was the only vascular complication trough the study (2.6
      % of patients) but no significant difference was seen between the two groups. In
      conclusion, our study showed the efficacy of fluoroscopy in increasing the proper
      femoral artery puncture, and although it did not show significant improvement in
      vascular complications, the method should be regard as an accurate guide for
      femoral access.

PMID- 23959380
TI  - Infant distress and development of functional gastrointestinal disorders in
      childhood: is there a connection?

PMID- 23959381
TI  - Autophagy is required for mitochondrial function, lipid metabolism, growth, and
      fate of KRAS(G12D)-driven lung tumors.
AB  - Evidence suggests that the role of autophagy in tumorigenesis is context
      dependent. Using genetically engineered mouse models (GEMMs) for human non-small
      cell lung cancer (NSCLC), we found that deletion of the essential autophagy gene,
      Atg7, in KRAS(G12D)-driven NSCLC inhibits tumor growth and converts adenomas and
      adenocarcinomas to benign oncocytomas characterized by the accumulation of
      respiration-defective mitochondria. Atg7 is required to preserve mitochondrial
      fatty acid oxidation (FAO) to maintain lipid homeostasis upon additional loss of
      Trp53 in NSCLC. Furthermore, cell lines derived from autophagy-deficient tumors
      depend on glutamine to survive starvation. This suggests that autophagy is
      essential for the metabolism, growth, and fate of NSCLC. 

PMID- 23959382
TI  - The influence of G-quadruplex structure on DNA-based asymmetric catalysis using
      the G-quadruplex-bound cationic porphyrin TMPyP4.Cu.
AB  - The DNA G-quadruplex-binding porphyrin TMPyP4.Cu was found to form efficient
      hybrid catalysts for DNA-based asymmetric catalysis when bound to DNA G
      quadruplexes. Nucleobase substitution experiments using human telomere-derived G
      quadruplex sequences suggest binding of the porphyrin on the 3'-face. 

PMID- 23959383
TI  - Systematic investigation of the mechanical properties of pure silica zeolites:
      stiffness, anisotropy, and negative linear compressibility.
AB  - While the energetic stability of the large number of possible SiO2 polymorphs has
      been widely addressed by both experimental and theoretical studies, there is a
      real dearth of information on their mechanical properties. We performed a
      systematic study of the elastic properties of 121 pure silica zeolites, including
      both experimentally synthesized and hypothetical structures, by means of density
      functional theory calculations. We found that most frameworks exhibit high
      elastic anisotropy, and the experimentally synthesized structures are among the
      most mechanically stable ones. We propose to extend the "feasibility" criterion
      proposed in earlier literature to include elastic anisotropy, allowing to further
      reduce the number of possible targets for synthesis of SiO2 polymorphs. We also
      predict that a small number of hypothetical pure silica zeolites present large
      negative linear compressibility (NLC), which we link to the wine-rack motif of
      their framework. 

PMID- 23959384
TI  - Ultrastructure of preimaginal stages of Piophila megastigmata  McAlpine, 1978
      (Diptera, Piophilidae): a fly of forensic  importance.
AB  - Piophila Fallen, 1810 is a genus of small flies composed of two species: Piophila
      casei (P. casei ) (Linnaeus, 1758), worldwide distributed, and Piophila
      megastigmata (P. megastigmata ) McAlpine, 1978, recently referred in the
      Palaearctic Region, from the Iberian Peninsula. Both species share ecological
      niche and are very interesting for forensic purposes, since they are present in
      carrion in advance stages of decay and have been found to be related to human
      corpses. The immature stages of P. megastigmata have ever been described, so this
      paper gives the ultrastructural morphologies of all preimaginal stages of P.
      megastigmata studied by light microscopy and scanning electron microscopy (SEM).
      Particular attention is given to pseudocephalon features-antenna, maxillary
      palps, facial mask, etc.-cephalopharyngeal skeleton, anterior and posterior
      spiracles, tegumentary sculpturing, and anal division among others. A comparative
      analysis of the main distinguishing features is made in order to understand how
      those features evolve along the developmental process, while larvae II and III
      are morphologically similar to each other, the larva I shows particular features.
      Larvae of all stages and pupae are easily distinguishable from other Diptera of
      forensic importance just based on the presence of trichoid sensilla associated to
      respiratory slits, instead of peristigmatig tufts, as well as on thewell-known
      disposition of anal papillae. The shapes of both dorsal edge at the basal part of
      mouthhook and dorsal bridge of cephalopharyngeal skeleton, and the tegumental
      ornamentationmay be considered as good features to distinguish the Piophila
      species, especially for P. megastigmata and P. casei . At the SEM level, shape,
      number, and arrangement of oral combs, oral ridges, sensilla of maxillary palpus,
      papillae of anterior spiracle, scales of spiracular field, and posterior
      spiracles represent good features to distinguish P. megastigmata from P. casei,
      but further studies will be necessary in West-Paleartic specimens of latter
      species. The key for identifying third instar larvae of forensically important
      Piophilidae in the Iberian Peninsula has been updated to include P. megastigmata.

PMID- 23959385
TI  - Genotyping and phylogenetic analysis of Acanthamoeba  isolates associated with
      keratitis.
AB  - We examined a partial SSU-rDNA sequence from 20 Acanthamoeba isolates associated
      with keratitis infections. The phylogenetic tree inferred from this partial
      sequence allowed to assign isolates to genotypes. Among the 20 isolates examined,
      16 were found to be of the T4 genotype, 2 were T3, 1 was a T5, and 1 was a T2,
      confirming the predominance of T4 in infections. However, the study highlighted
      other genotypes more rarely associated with infections, particularly the T2
      genotype. Our study is the second one to detect that this genotype is associated
      with keratitis. Additionally, the phylogenetic analyses showed five main emerging
      clusters, T4/T3/T11, T2/T6, T10/T12/T14, T13/T16, and T7/T8/T9/T17, regularly
      obtained whichever method was used. A similar branching pattern was found when
      the full rDNA sequence was investigated.

PMID- 23959386
TI  - Structural and biochemical studies of a recombinant 25.5 kDa  glutathione
      transferase of Taenia solium metacestode  (rTs25GST1-1).
AB  - In this work, we studied a recombinant mu-class glutathione transferase of 25.5
      kDa from Taenia solium metacestode (rTs25GST1-1) that follows Michaelis-Menten
      kinetics with 1-chloro-2,4-dinitrobenzene (CDNB). The kinetic parameters obtained
      for rTs25GST1-1 with CDNB and GSH were V(max) =12.04 MUmol/min/mg and K(m)=1.38
      mM, and V(max) =10.20 MUmol/min/mg and K(m)=0.90, respectively. The optimal
      activity was found at pH 8 in the 37-40  degrees C temperature range. Circular
      dichroism studies for rTs25GST1-1 at different pH showed that it maintains a
      typical alpha-helix structure between pH 6.5-7.5, but loses it between pH 8 and
      8.5. Thermal CD assays showed rTs25GST1-1 barely changed its secondary structure.
      Unfolding/refolding assays showed that rTs25GST1-1 retained its structure up to
      40  degrees C without loss of its activity. Additionally, exposure of rTs25GST1-1
      to cumene hydroperoxide did not produce significant changes in its structure and
      only affected 50% of its activity.

PMID- 23959387
TI  - Canakinumab (Ilaris) for systemic juvenile idiopathic arthritis.

PMID- 23959388
TI  - Bedaquiline (Sirturo) for multidrug-resistant tuberculosis.

PMID- 23959389
TI  - In brief: nimodipine oral solution (Nymalize).

PMID- 23959390
TI  - [The eye, vision and vertigo].
AB  - Although ocular alterations alone rarely cause vertigo, the ophthalmologist can
      play an important role in the interdisciplinary context by testing visual
      function. Assessment of ocular motility is the most important individual
      examination in the diagnostic evaluation of vertigo. Methods that analyze
      specific visual functions, like the dynamic visual acuity test, may play an
      important role in the future. In addition to neuro-ophthalmologic disorders,
      ocular alterations are also receiving increasing attention. They are postulated
      to be a key element in the development of multifactorial age-related vertigo.
      However, further investigation is required to confirm this supposition and to
      define the influence of disturbances in specific visual qualities, e.g. visual
      acuity, visual field, binocular vision, anisometropia, multifocal correction,
      higher order aberrations and metamorphopsia.

PMID- 23959391
TI  - [Video head impulse test or caloric irrigation?. Contemporary diagnostic tests
      for vestibular schwannoma].
AB  - The video head impulse test (vHIT) is a new method for investigating vestibular
      function that is currently poorly studied in terms of its value for clinical
      diagnosis in otolaryngology. Both the caloric irrigation and vHIT serve to
      evaluate the horizontal vestibulo-ocular reflex. In the present study, caloric
      irrigation and vHIT were compared in 46 patients with vestibular schwannoma.
      Caloric irrigation exhibits a higher sensitivity than vHIT (72% versus 41%) and
      both tests show only a moderate correlation. Tumor size and hearing level was
      significantly correlated with caloric abnormalities but not with vHIT findings.
      Since caloric irrigation and vHIT measure the hVOR in low and high frequency
      ranges, respectively, these tests have to be considered complementary and are
      valuable in both diagnostics and therapeutic decisions.

PMID- 23959393
TI  - A Pd-diimine catalytic inimer for synthesis of polyethylenes of hyperbranched-on
      hyperbranched and star architectures.
AB  - A Pd-diimine catalytic inimer containing uniquely catalytic, initiating, and
      monomeric functionalities in one catalyst molecule is designed. It enables the
      first self-condensing vinyl copolymerization of ethylene, leading to
      polyethylenes of a hyperbranched-on-hyperbranched architecture. Meanwhile, it
      also facilitates the synthesis of star polyethylenes by tandem UV-coordinative
      polymerization. 

PMID- 23959392
TI  - Stakeholder validation of a model of readiness for transition to adult care.
AB  - IMPORTANCE: That too few youth with special health care needs make the transition
      to adult-oriented health care successfully may be due, in part, to lack of
      readiness to transfer care. There is a lack of theoretical models to guide
      development and implementation of evidence-based guidelines, assessments, and
      interventions to improve transition readiness. OBJECTIVE: To further validate the
      Social-ecological Model of Adolescent and Young Adult Readiness to Transition
      (SMART) via feedback from stakeholders (patients, parents, and providers) from a
      medically diverse population in need of life-long follow-up care, survivors of
      childhood cancer. DESIGN: Mixed-methods participatory research design. SETTING: A
      large Mid-Atlantic children's hospital. PARTICIPANTS: Adolescent and young adult
      survivors of childhood cancer (n = 14), parents (n = 18), and pediatric providers
      (n = 10). MAIN EXPOSURES: Patients and parents participated in focus groups;
      providers participated in individual semi-structured interviews. MAIN OUTCOMES
      AND MEASURES: Validity of SMART was assessed 3 ways: (1) ratings on importance of
      SMART components for transition readiness using a 5-point scale (0-4; ratings >2
      support validity), (2) nominations of 3 "most important" components, and (3)
      directed content analysis of focus group/interview transcripts. RESULTS:
      Qualitative data supported the validity of SMART, with minor modifications to
      definitions of components. Quantitative ratings met criteria for validity;
      stakeholders endorsed all components of SMART as important for transition. No
      additional SMART variables were suggested by stakeholders and the "most
      important" components varied by stakeholders, thus supporting the
      comprehensiveness of SMART and need to involve multiple perspectives. CONCLUSIONS
      AND RELEVANCE: SMART represents a comprehensive and empirically validated
      framework for transition research and program planning, supported by survivors of
      childhood cancer, parents, and pediatric providers. Future research should
      validate SMART among other populations with special health care needs.

PMID- 23959394
TI  - 2,3'-diamino-4,4'-stilbenedicarboxylic acid sensitizer for dye-sensitized solar
      cells: quantum chemical investigations.
AB  - The metal-free organic dye sensitizer 2,3'-diamino-4,4'-stilbenedicarboxylic acid
      has been investigated for the first time for dye-sensitized solar cell
      applications. Density functional theory (DFT) and time-dependent DFT (TD-DFT)
      calculations (performed using the hybrid functional B3LYP) were carried out to
      analyze the geometry, electronic structure, polarizability, and
      hyperpolarizability of 2,3'-diamino-4,4'-stilbenedicarboxylic acid used as a dye
      sensitizer. A TiO2 cluster was used as a model semiconductor when attempting to
      determine the conversion efficiency of the selected dye sensitizer. Our TD-DFT
      calculations demonstrated that the twenty lowest-energy excited states of 2,3'
      diamino-4,4'-stilbenedicarboxylic acid are due to photoinduced electron-transfer
      processes. Moreover, interfacial electron transfer between a TiO2 semiconductor
      electrode and the dye sensitizer occurs through electron injection from the
      excited dye to the semiconductor's conduction band. Results reveal that metal
      free 2,3'-diamino-4,4'-stilbenedicarboxylic acid is a simple and efficient
      sensitizer for dye-sensitized solar cell applications.

PMID- 23959395
TI  - Performance assessment of semiempirical molecular orbital methods in the
      structural prediction of Sb(III) and Bi(III) complexes.
AB  - In this paper we carried out a systematic study in order to assess the quality of
      some semiempirical methods (AM1, PM3 and PM6), comparing predicted structural
      properties of many Sb(III) and Bi(III) complexes with the corresponding
      experimental data, indicating which one is more appropriate to describe the
      structure of such compounds. Root-mean squared deviation (RMSD) and unsigned mean
      error (UME) were used to evaluate the accuracy of the semiempirical methods to
      predict the ground state geometries of complexes with many ligand types. Our
      results have shown that, in general, PM3 predicts more accurately the geometry of
      Sb(III) complexes, being considered by us as the method of choice to study
      Sb(III) complexes with a great variety of ligands. PM6 is indicated as the method
      of choice to study Bi(III) complexes with many types of ligands and also to study
      Sb(III) thiocompounds, even though PM6 showed an inability to reproduce Sb-N
      bonds for complexes with flexible ligands, presenting an average deviation of
      71.5 % compared the X-ray data.

PMID- 23959396
TI  - HER3, p95HER2, and HER2 protein expression levels define multiple subtypes of
      HER2-positive metastatic breast cancer.
AB  - Trastuzumab is effective in the treatment of HER2/neu over-expressing breast
      cancer, but not all patients benefit from it. In vitro data suggest a role for
      HER3 in the initiation of signaling activity involving the AKT-mTOR pathway
      leading to trastuzumab insensitivity. We sought to investigate the potential of
      HER3 alone and in the context of p95HER2 (p95), a trastuzumab resistance marker,
      as biomarkers of trastuzumab escape. Using the VeraTag(r) assay platform, we
      developed a dual antibody proximity-based assay for the precise quantitation of
      HER3 total protein (H3T) from formalin-fixed paraffin-embedded (FFPE) breast
      tumors. We then measured H3T in 89 patients with metastatic breast cancer treated
      with trastuzumab-based therapy, and correlated the results with progression-free
      survival and overall survival using Kaplan-Meier and decision tree analyses that
      also included HER2 total (H2T) and p95 expression levels. Within the sub
      population of patients that over-expressed HER2, high levels of HER3 and/or p95
      protein expression were significantly associated with poor clinical outcomes on
      trastuzumab-based therapy. Based on quantitative H3T, p95, and H2T measurements,
      multiple subtypes of HER2-positive breast cancer were identified that differ in
      their outcome following trastuzumab therapy. These data suggest that HER3 and p95
      are informative biomarkers of clinical outcomes on trastuzumab therapy, and that
      multiple subtypes of HER2-positive breast cancer may be defined by quantitative
      measurements of H3T, p95, and H2T.

PMID- 23959397
TI  - Immunoliposome encapsulation increases cytotoxic activity and selectivity of
      curcumin and resveratrol against HER2 overexpressing human breast cancer cells.
AB  - Natural compounds have been studied as a source of countless bioactive compounds
      with diverse activities. Among them, many dietary phytochemicals have been
      thoroughly studied for their cytotoxic or apoptotic effects in several cellular
      models in order to explain their anticancer capacity. Curcumin and resveratrol
      are two natural compounds with a large body of evidence showing their cytotoxic
      activity against a wide variety of cancer cells; however, their poor absorption,
      bioavailability, and low selectivity have limited their clinical use. With the
      aim of improving bioavailability and selectivity, the antiproliferative effects
      of free-, liposomed-, and immunoliposomed-curcumin and/or resveratrol
      formulations have been compared in two human breast cancer cell lines with
      different HER2 expression levels. The results demonstrate that when HER2-targeted
      immunoliposomes are coupled to trastuzumab there is a dramatic increase in the
      antiproliferative effects of curcumin and resveratrol in HER2 positive human
      breast cancer cells in comparison to regular liposomed or free forms, indicating
      an increase of its therapeutic effect. The enhancement of the cytotoxic effects
      was also correlated to the uptake of curcumin at intracellular level, as shown by
      using ImageStream technique. The striking efficacy of the immunoliposomed
      formulation containing both resveratrol and curcumin suggests a multitargeted
      mechanism of action that deserves further study. These findings show the
      potential of HER2-targeted nanovesicles to develop new drug delivery systems for
      cancer therapy based on these compounds and justify further preclinical trials.

PMID- 23959398
TI  - Application of solvent modified PEDOT:PSS to graphene electrodes in organic solar
      cells.
AB  - Graphene has been proposed as a promising transparent conducting electrode
      material in organic photovoltaic (OPV) solar cells to substitute the widely used
      indium tin oxide (ITO). Various studies have reported OPV devices with graphene
      electrodes showing comparable performances to ITO-based OPV cells. However, the
      fabrication reliability or device yield has not been widely discussed. In our
      investigation it was found that graphene-based OPVs tend to have much lower
      device yield than the ITO-based ones if similar fabrication processes are used.
      One possible reason could be due to the challenge faced in obtaining a uniform
      coating of PEDOT:PSS hole injection layer (HIL) on graphene. In fact, several
      attempts have been made to overcome this challenge. In this work, we report a
      facile method of solvent modification of PEDOT:PSS to achieve a homogeneous
      coating on graphene. A significant enhancement in the device yield was observed
      as compared to devices using normal aqueous solution based PEDOT:PSS;
      nevertheless, it was still only ~50%. Further improvement was made by adding an
      additional electron blocking layer (EBL), molybdenum trioxide, after the coating
      of PEDOT:PSS. The observation in this work calls for further investigation to
      understand the role played by the HIL or EBL in graphene-based OPV devices. 

PMID- 23959399
TI  - PMS6: A Fast Algorithm for Motif Discovery.
AB  - We propose a new algorithm, PMS6, for the (l, d)-motif discovery problem in which
      we are to find all strings of length l that appear in every string of a given set
      of strings with at most d mismatches. The run time ratio PMS5/PMS6, where PMS5 is
      the fastest previously known algorithm for motif discovery in large instances,
      ranges from a high of 2.20 for the (21,8) challenge instances to a low of 1.69
      for the (17,6) challenge instances. Both PMS5 and PMS6 require some amount of
      preprocessing. The preprocessing time for PMS6 is 34 times faster than that for
      PMS5 for (23,9) instances. When preprocessing time is factored in, the run time
      ratio PMS5/PMS6 is as high as 2.75 for (13,4) instances and as low as 1.95 for
      (17,6) instances.

PMID- 23959400
TI  - Re: Intracutaneous sterile water injection versus oral paracetamol for renal
      colic during pregnancy: a randomized controlled trial. Int Urol Nephrol 2013;
      45:321-325, DOI 10.1007/s11255-013-0405-3.

PMID- 23959401
TI  - Renal resistive index as a marker of vascular damage in cardiovascular diseases.
AB  - The article presents changeability of renal resistive index (RRI) in various
      cardiovascular diseases and considers the usefulness of the marker and
      interpretational difficulties of the index. The values of RRI are not specific to
      an individual disease, but in a selected group of patients, it seems to be a
      perfect marker of cardiovasculorenal changes and a predictor of rapid loss of a
      renal function. The RRI usually does not reflect the vascular resistance, but is
      dependent on total and local vascular bed compliance changing with age, in the
      course of consecutive diseases and the influence of drugs. Under specific
      conditions, RRI appears to be a good marker of vascular damage. This review
      summarizes current concepts in RRI interpretation against the cardiovascular
      pathologies, focusing on the vascular damage association with regard to the
      complex nature of RRI value variability.

PMID- 23959403
TI  - Cathodic catalysts in bioelectrochemical systems for energy recovery from
      wastewater.
AB  - Bioelectrochemical systems (BESs), in which microorganisms are utilized as a self
      regenerable catalyst at the anode of an electrochemical cell to directly extract
      electrical energy from organic matter, have been widely recognized as a promising
      technology for energy-efficient wastewater treatment or even for net energy
      generation. However, currently BES performance is constrained by poor cathode
      reaction kinetics. Thus, there is a strong impetus to improve the cathodic
      catalysis performance through proper selection and design of catalysts. This
      review introduces the fundamentals and current development status of various
      cathodic catalysts (including electrocatalysts, photoelectrocatalysts and
      bioelectrocatalysts) in BES, identifies their limitations and influential
      factors, compares their catalytic performances in terms of catalytic efficiency,
      stability, selectivity, etc., and discusses the possible optimization strategies
      and future research directions. Special focus is given on the analysis of how the
      catalytic performance of different catalysts can be improved by fine tuning their
      physicochemical or physiological properties. 

PMID- 23959402
TI  - Red cell distribution width is associated with mortality in kidney transplant
      recipients.
AB  - BACKGROUND: Red cell distribution width (RDW), a parameter routinely reported as
      part of the complete blood count, is associated with increased morbidity and
      mortality risk in different patient populations. No published data are available
      about the association between RDW and mortality in kidney transplant recipients.
      METHODS: We collected socio-demographic, clinical parameters, medical and
      transplant history and laboratory data at baseline in 723 prevalent kidney
      transplant recipients between June and October 2008 [mean age 51 +/- 13 (SD)
      years, 56 % men, 21 % diabetics]. Associations between baseline RDW values and
      all-cause mortality over 3 years were examined in unadjusted and adjusted models.
      RESULTS: Increasing RDW was associated with increased mortality in both
      unadjusted [(HR(1 % increase) = 1.63; 95 % CI 1.41-1.89) and (HR(>median) = 2.74;
      95 % CI 1.68-4.48)] and fully adjusted models [(HR(1 % increase) = 1.60; 95 % CI
      1.27-1.89) and (HR(>median) = 1.33; 95 % CI 0.76-2.35)]. In reclassification
      analyses, RDW improved the predictive value of all-cause mortality prediction
      models [the net reclassification improvement (NRI) was 0.189; p < 0.001].
      CONCLUSIONS: RDW, a cheap and readily available but largely neglected parameter
      independently, predicts mortality in prevalent kidney transplant recipients and
      could potentially been used in everyday risk assessment of kidney transplant
      recipients.

PMID- 23959404
TI  - Sciatic nerve compression by an extrapelvic cyst secondary to wear debris after a
      cementless total hip arthroplasty: A case report and literature review.
AB  - INTRODUCTION: Polyethylene (PE) wear debris after total hip arthroplasty (THA)
      may cause formation of a soft tissue mass due to inflammatory reaction. To the
      best of our knowledge we report the first case in whom the diagnosis was made
      after examination of the hip, pelvis and lumbar spine with detailed radiological
      methods and the plain radiographs showed no signs of loosening of the THA.
      PRESENTATION OF CASE: We report a 52 years-old woman who presented with a cyst
      causing sciatic irritation in her gluteal region due to wear debris after THA.
      Magnetic resonance imaging (MRI) was useful in detecting the cyst. Resolution of
      the cyst occured after subtotal cystectomy and revision of the acetabular
      components. DISCUSSION: Although plain radiographs can show signs of the
      underlying pathology; such as osteolysis, loosening of the components and wear of
      the PE liner, they are unable to detect cystic lesions. Cystic lesions may be an
      early sign of wear debris. CONCLUSION: This case shows us that sciatic neuropathy
      with no evidence of nerve root impingement on lumbar MRI in a patient with THA
      requires also examination of the hip and pelvis with detailed radiological
      methods, such as MRI, in addition to plain radiography. Removal of the source of
      debris via revision surgery following subtotal cystectomy leads to the resolution
      of the remaining portion of the cyst and also relief of the symptoms of sciatic
      nerve compression.

PMID- 23959405
TI  - Sentinel node mapping in high risk endometrial cancer after laparoscopic
      supracervical hysterectomy with morcellation.
AB  - INTRODUCTION: Occult endometrial cancer after supracervical hysterectomy is very
      uncommon. Even if optimal management of those rare cases is still unproven, to
      guide the need for further therapies, restaging should be recommended in this
      situation. PRESENTATION OF CASE: We report of a 60-year old woman with occult
      high risk endometrial cancer after supracervical hysterectomy with morcellation.
      We describe the feasibility of laparoscopic intraoperative sentinel node
      identification with cervical stump removing to restage the suspicious early stage
      high risk endometrial cancer. DISCUSSION: In high risk endometrial cancer
      surgical restaging is important, considering that 10-35% of cases can present
      pelvic nodal metastasis. To reduce the treatment related morbidity maintaining
      the benefit of surgical staging, with a negative preoperative PET/CT, we
      performed a laparoscopic SN mapping with cervical stump removing. CONCLUSION:
      This report highlight the fact that SN mapping with cervical injection is a
      feasible and safe technique also without the uterine corpus after supracervical
      hysterectomy with morcellation.

PMID- 23959406
TI  - Cerebral arteriovenous malformation presenting with polycythemia vera: A case
      report and literature review.
AB  - INTRODUCTION: Cerebral arteriovenous malformations (AVM) usually present with
      headache, hemorrhage, or seizure. Erythropoietin (EPO) has demonstrated
      protective effects against ischemia within the CNS. PRESENTATION OF CASE: The
      authors report a patient with a cerebral AVM and concurrent polycythemia
      associated with elevated serum EPO. Systemic EPO levels declined acutely after
      resection of the patient's AVM, and the polycythemia resolved in the following
      months. DISCUSSION: Polycythemia secondary to a cerebral AVM, in the absence of
      extra-cerebral vascular lesions, has not been described in the literature.
      CONCLUSION: The authors explore the mechanisms by which this patient's cerebral
      AVM could have induced EPO production within the brain, manifesting as
      polycythemia.

PMID- 23959407
TI  - Giant extra gastrointestinal stromal tumor of lesser omentum obscuring the
      diagnosis of a choloperitoneum.
AB  - INTRODUCTION: Herein we present an extremely rare case of a giant extra
      gastrointestinal stromal tumor (EGIST) of the lesser omentum obscuring the
      diagnosis of a choloperitoneum. PRESENTATION OF CASE: A 79 years old female was
      admitted to our hospital with symptoms of vomiting and epigastric pain. Abdominal
      computer tomography revealed a sizable formation that was diagnosed as a tumor of
      the pancreas. In laparotomy, a choloperitoneum was diagnosed as the cause of
      patient's symptoms. A tumor adherent firmly to the lesser curvature of stomach
      was also discovered. Cholecystectomy and subtotal gastrectomy were performed.
      Histologically, the tumor was diagnosed as a EGIST of the lesser omentum. The
      patient did not receive any adjuvant therapy and after two years of follow up she
      is without any recurrence. DISCUSSION: Omental EGISTs may remain clinically
      silent despite the large tumor's size. It is difficult to differentiate a EGIST
      in the lesser omentum from a GIST of the lesser curvature of the stomach, despite
      the use of advanced radiological imaging techniques. Our case of a giant EGIST of
      lesser omentum obscuring the diagnosis of acute choloperitoneum is the only one
      reported in literature. CONCLUSION: EGISTs that arise from the omentum are very
      rare and complete surgical resection is the only effective treatment approach.
      Adjuvant therapy following resection of localized disease has become standard of
      care in high risk cases.

PMID- 23959408
TI  - Primary paraganglioma of seminal vesicle.
AB  - INTRODUCTION: Paragangliomas are rare tumors arising from neural crest tissue
      located outside the adrenal gland. Primary seminal vesicle paraganglioma is
      extremely rare entity. PRESENTATION OF CASE: A 26-year-old male patient presented
      with symptoms and signs of acute appendicitis where a CT of abdomen and pelvis
      showed an inflamed appendix and incidental finding of left seminal vesicle mass.
      The patient underwent uneventful laparoscopic appendectomy followed by
      transrectal ultrasound (TRUS) guided seminal vesicle biopsies. Histopathology
      revealed a neuroendocrine neoplasm consistent with paraganglioma. Surgical
      excision of the left seminal vesicle was carried out. DISCUSSION: Paraganglioma
      of genitourinary tract is rare. The urinary bladder is the most common site,
      followed by the urethra, pelvis and ureter. Seminal vesicle paragangliomas were
      reported in association with other genitourinary organ involvement such as
      bladder and prostate. Isolated seminal vesicle paraganglioma is extremely rare
      and surgical excision remains the standard treatment for localized paraganglioma.
      CONCLUSION: Primary tumors of seminal vesicle are rare and represent a diagnostic
      challenge. Differential diagnosis includes a list of benign and malignant tumors.
      Primary seminal vesicle paraganglioma is a rare but important diagnosis to be
      included in the differential diagnosis.

PMID- 23959409
TI  - Phlegmasia caerulea dolens secondary to pelvic plasmacytoma and left femoral deep
      vein thrombosis.
AB  - INTRODUCTION: Phlegmasia caerulea dolens (PCD) is a clinical syndrome caused by
      venous obstruction leading to peripheral limb ischaemia. It can ultimately lead
      to venous gangrene, amputation or death in 25% of cases. PRESENTATION OF CASE: A
      52-year-old man with a background of myeloma developed PCD secondary to an
      obstructing plasmacytoma and left femoral vein deep vein thrombosis (DVT). These
      were treated with combined radiotherapy and anticoagulation, with resolution of
      the patient's symptoms. His recovery was complicated by the development of
      heparin-induced thrombocytopenia (HIT) and cutaneous vasculitis. DISCUSSION: Both
      plasmacytoma and DVT are recognised complications of myeloma. This is, to our
      knowledge, the first description of these phenomena in combination causing PCD.
      The combination of venous stasis from the obstructing plasmacytoma and
      hypercoagulability from the underlying myeloma may have contributed to clot
      formation. A multifaceted treatment approach was required which aimed at
      improving venous flow via radiotherapy to the plasmacytoma and dissolving the
      obstructing clot with anticoagulant therapy. CONCLUSION: PCD has a high mortality
      and morbidity. Recognition is important to avoid an incorrect diagnosis of
      arterial occlusion and inappropriate surgical intervention. Treatment must be
      focused on removing the offending causes.

PMID- 23959410
TI  - Renal cell carcinoma with concomitant solid pseudopapillary tumor of the
      pancreas: A case report.
AB  - INTRODUCTION: Solid pseudopapillary tumor (SPT) of pancreas is an unusual low
      grade malignant epithelial tumor that usually occurs in young women and can be
      treated with surgical resection. Renal cell carcinoma (RCC) is the most common
      solid lesion of the kidney and primarily a disease of the elderly patient.
      PRESENTATION OF CASE: In this article we present a case of RCC with concomitant
      SPT of the pancreas who was treated successfully with a radical nephrectomy and
      distal pancreatectomy. DISCUSSION: RCC with concomitant SPT may associated in
      beta-catenin gene mutation. But no prior reports have described RCC with
      concomitant SPT of the pancreas in the same patient. CONCLUSION: To the best of
      our knowledge, this is the first report of RCC with concomitant SPT of the
      pancreas in the same patient.

PMID- 23959411
TI  - Hygroma following endovascular femoral aneurysm exclusion: A case report.
AB  - INTRODUCTION: Endovascular treatment of aneurysms in the superficial femoral
      artery (SFA) and popliteal segments is a suggested alternative to open surgical
      repair. Careful selection of patients for endovascular treatment of SFA aneurysms
      is mandatory. PRESENTATION OF CASE: A complication due to endovascular stent
      graft treatment in an 80-year old male with a 6 cm aneurysm in the SFA is
      presented. Hygroma developed after a partially unintended extravascular placed
      stent-graft. Two consecutive explorations resulted in a femoro-popliteal
      Polytetrafluoro-ethylene (PTFE) by-pass graft as the final solution. DISCUSSION:
      Several explanations for the patient's complications are suggested. CONCLUSION: A
      primary femoral-femoral/popliteal by-pass might be the best solution in SFA
      aneurysms due to risk of stent complications.

PMID- 23959412
TI  - Remote contralateral intraparenchymal hemorrhage after overdrainage of a chronic
      subdural hematoma.
AB  - INTRODUCTION: Chronic subdural hematoma (cSDH) is frequently seen by
      neurosurgeons. Treatment often includes evacuation of the subdural hematoma (SDH)
      through one or two burr holes and placement of a drain in the subdural space to
      further evacuate subdural fluid and prevent reaccumulation of blood during the
      immediate postoperative period. Complications associated with this type of
      drainage include fluid and blood reaccumulation, tension pneumocephalus, seizures
      and subdural empyema. PRESENTATION OF CASE: The author presents a case in which
      aggressive CSF overdrainage most likely led to acute severe intracranial
      hypotension, causing the collapse of the contralateral bridging veins and
      ultimately resulting in venous insufficiency and hemorrhagic infarction. The
      remote intracerebral hemorrhages were suspected to be due to CSF overdrainage
      through the subdural drain, so the drain was immediately removed. After drain
      removal, the patient's neurologic status improved and his hemiplegia disappeared
      within 4h. A follow-up head CT scan 1 month later revealed resolution of his
      subdural fluid collection and right-sided intraparenchymal hemorrhages. He
      returned to work 1 month later in good condition. DISCUSSION: Although many
      authors have examined factors affecting the success of cSDH drainage procedures,
      there are few reports about the risks of overdrainage and little information
      available about drainage volume. This report links excessive cSDH drainage of
      with a remote contralateral intraparenchymal hemorrhage, a complication that has
      been noted only twice previously, and neither report suggested the mechanism for
      occurrence of the hemorrhage, or specified the amount of drainage. CONCLUSION:
      Subdural drainage should be carefully monitored to avoid overdrainage.

PMID- 23959413
TI  - Ruptured distal middle cerebral artery aneurysm: Case report.
AB  - INTRODUCTION: This report describes a rare case of a distal middle cerebral
      artery (dMCA) aneurysm. PRESENTATION OF CASE: That developed a right
      intracerebral haematoma and subarachnoid haemorrhage. It was treated by surgical
      exploration and clipping via pterional approach. DISCUSSION: Clinical findings
      and surgical approaches of dMCA aneurysm are different from proximal middle
      cerebral artery (MCA) aneurysms. Microneurosurgical clipping is the most
      effective treatment of dMCA aneurysm. CONCLUSION: We comprehensively review the
      literature related to these rare aneurysms within the temporal lobe, surgical
      anatomy of the dMCA aneurysm.

PMID- 23959414
TI  - A case of Menetrier's disease localized to the gastric antrum without
      helicobacter infection or hypoalbuminemia.
AB  - INTRODUCTION: Menetrier's disease (MD) is a rare gastric disorder closely
      associated with Helicobacter pylori infection characterized by enlarged gastric
      mucosal folds and hyperplasia of surface mucus-secreting cells classically
      localized to the gastric body. This disease has significant morbidity and
      mortality secondary to hypoproteinemia, gastric obstruction, hemorrhage, and
      increased risk of adenocarcinoma. PRESENTATION OF CASE: We report a 53-year-old
      female who presented with severe epigastric pain, anorexia, weight loss, and
      prandial vomiting with serum albumin and chloride levels in the normal range.
      After serial upper endoscopy with biopsy identified nonspecific inflammatory
      changes in the absence of H. pylori, surgical exploration was performed with
      intraoperative tissue samples revealing nondysplastic, foveolar hyperplasia.
      Gastric antrectomy was performed with gross and microscopic examination verifying
      the diagnosis of MD. DISCUSSION: The unusual presentation of this case
      differentiates it from other known cases due to the rare localization of the
      disease to the gastric antrum, the absence of H. pylori infection, and the
      uncharacteristically normal serum albumin level on presentation. CONCLUSION: This
      case may represent an unreported subset of MD where limited surgical resection is
      demonstrated to offer an exceptional outcome.

PMID- 23959415
TI  - Analysis of single-staged resection of a fourth ventricular tumor via a combined
      infratentorial-supracerebellar and telovelar approach: Case report and review of
      the literature.
AB  - INTRODUCTION: The authors explore a combined infratentorial-supracerebellar and
      telovelar approach in an adult, while avoiding vermian-splitting methods for a
      large, midline, fourth-ventricular tumor, unapproachable though a single
      traditional route. Experience with a combined surgical approach for pediatric
      patients has been published, but the authors believe that describing this
      combined method in an adult will provide a preliminary experience for further
      exploration of this approach in other adult patients. PRESENTATION OF CASE: The
      authors present a review of the literature along with the case of a 60-year-old
      man with slight ataxia who presented with a 1-month history of gait difficulty
      and memory lapse. His MRI of the brain showed mild hydrocephalus and a large
      tumor of the fourth ventricle. Surgical removal through a suboccipital craniotomy
      was attempted, and part of the tumor overlying the tectum and the superior
      cerebellar velum was removed without difficulty. However, despite inferior
      retraction of the vermis, which allowed further resection of the tumor from the
      fourth ventricle, residual tumor in the caudal surgical resection cavity was
      present. Partial transection of the vermis was considered, but avoided because of
      potential neurological deficits. Instead, the authors redirected their approach
      and exposed the residual tumor by transecting the inferior medullary velum and
      removed additional tumor while avoiding the floor of the fourth ventricle. The
      infratentorial-supracerebellar and telovelar approach resulted in total gross
      resection of the tumor. DISCUSSION: For patients with large midline tumors that
      arise from the superior vermis or the quadrigeminal plate and fill the upper
      third of the fourth ventricular space, this combined approach may offer a unique
      possibility of safe tumor removal. CONCLUSION: This case demonstrates the benefit
      of a combined approach for a select group of patients.

PMID- 23959416
TI  - A difficult case of retrieval of an aortic valve and balloon during a
      transcatheter aortic valve implantation.
AB  - INTRODUCTION: Transcatheter aortic valve implantation (TAVI) represents an
      emerging therapy for valve replacement in patients not suitable for traditional
      open repair. As awareness of the procedure grows, case numbers are increasing
      worldwide. Though this procedure represents a less invasive approach to aortic
      valve replacement, it is not without complications. PRESENTATION OF CASE: This
      case presentation describes a serious, previously unreported, complication
      incurred in an 83-year-old male in whom TAVI was attempted. During deployment of
      the valve at the aortic annulus, both the valve and accompanying balloon
      embolised into the thoracic aorta and this was further complicated by migration
      of the balloon into the abdominal aorta and an aortic dissection. The false lumen
      of the dissection at the level of the infrarenal aorta was tacked to the aortic
      adventitial wall using interrupted sutures through a laparotomy. A completion
      angiogram demonstrated that a flow limited dissection did extend up to both
      common iliac arteries. This was managed with balloon-expandable covered stents
      deployed in both common iliac arteries with satisfactory outcome. DISCUSSION:
      This case occurred as a combination of multiple factors that include lack of
      burst pacing and poor timing of the balloon inflation. The aortic balloon and the
      valve had to be removed urgently to avoid ventricular embolization of these
      structures that can result in a fatal situation. CONCLUSION: This case
      presentation describes the management of these complications using a combined
      open and endovascular approach in a well-equipped hybrid operating theatre,
      resulting in the patient survival.

PMID- 23959417
TI  - A case of solitary pulmonary metastasis of choroidal melanoma with an
      exceptionally long disease-free period.
AB  - INTRODUCTION: Choroidal melanoma is the most common primary malignant intraocular
      tumor in adults. And its metastatic spread has been considered to be hematogenous
      with the liver being the most common site, and a solitary pulmonary metastasis
      without hepatic involvement is quite rare. PRESENTATION OF CASE: We report the
      case of a 61-year-old woman with a solitary pulmonary metastasis from choroidal
      melanoma, which had been originally treated with enucleation 13 years ago. Video
      assisted thoracoscopic surgery (VATS) right upper lobectomy was performed for the
      right upper lobe tumor, which was histopathologically confirmed to be metastatic
      choroidal melanoma. DISCUSSION: Our case is quite unusual in 2 points; firstly, a
      solitary pulmonary metastasis without hepatic involvement is rare. Secondly, this
      mode of metastasis with an exceptionally long disease-free period (13 years) is
      also rare. CONCLUSION: A pulmonary metastasis from choroidal melanoma is
      described with reference to relevant literature.

PMID- 23959418
TI  - A true aneurysm of the superficial temporal artery: Is there an underlying pre
      disposition to such rarities?
AB  - INTRODUCTION: A 32 year old man presented to our vascular clinic with a lump over
      the left eyebrow. It had become larger in size and was cosmetically unacceptable.
      PRESENTATION OF CASE: Clinical examination of the lump demonstrated a pulsatile
      swelling consistent with an aneurysm of the superficial temporal artery (STA).
      Doppler ultrasound demonstrated arterial flow within the lump that could be
      controlled with pressure over the proximal branch of the vessel. The STA aneurysm
      was excised under local anaesthesia by ligation of the feeding and draining
      branches. It measured 3.4cm*3.7cm. Histological examination confirmed a rare
      finding of a true aneurysm of the STA. DISCUSSION: Aneurysms are classified into
      false or true types, with false aneurysms of the STA accounting for 95% of cases
      reported. It has therefore been suggested that true aneurysms of the STA may
      develop from a yet unknown pre-existing vessel condition. The histological
      findings in our case demonstrated myxoid/mucoid deposits replacing elastin fibres
      of the media layer, in addition to cystic lesions seen in the adventitia. These
      features were thought to be nonspecific but have been reported in rare conditions
      known as cystic adventitial disease and cystic medial necrosis. Such is their
      obscurity that we speculate that both of these may represent variations of the
      same underlying pathology. As myxoid/mucoid changes are also noted in more well
      known connective tissue disorders including Marfan's syndrome, imaging was
      arranged to screen our patient for thoracic and abdominal aneurysms. These proved
      negative and there were no Marfanoid features noted prior. CONCLUSION: Aneurysms
      of the STA are easily treated by surgical excision. This should be considered
      when they become large, painful or are cosmetically undesirable. Unusual
      histological findings in the specimen may indicate a connective tissue disorder
      that should be investigated if indicated.

PMID- 23959419
TI  - An unusual case caused by a common reason: Mondor's disease by oral
      contraceptives.
AB  - INTRODUCTION: Mondor's disease (MD) of the breast is a rare condition at breast
      clinics. We do not have enough data to establish its real prevalence. As a known
      data, most of the patients that were admitted to breast clinics are not breast
      cancer. Also MD is a rare entity and diagnosing this entity and informing the
      patient about it is very important. We present here this case to remind breast
      clinic practitioners that MD can be seen without trauma (neither surgical nor
      physical). Also clinical and radiological findings and the treatmentof the MD
      were discussed. PRESENTATION OF CASE: A 35 year old woman was admitted our clinic
      with cutaneous breast retraction. She had no risk for thrombosis else using oral
      contraceptives. Mondor's Disease was diagnosed and supported by radiological
      findings. Rheumatologic and hematologic causes were also explored. Patient healed
      in four weeks only with non-steroidal anti-inflammatory drug. DISCUSSION:
      Mondor's Disease is rarely related with breast cancer. This rare entity can be
      diagnosed with doubt and patient should be informed about it. Anti-coagulant
      treatment does not required if disease is idiopathic. CONCLUSION: Mondor's
      Disease should be reminded at a patient with retracted breast skin.

PMID- 23959420
TI  - Carotico-cavernous fistula: An educational case.
AB  - INTRODUCTION: We present a case of direct carotico-cavernous fistula (CCF) and
      its successful treatment. PRESENTATION OF CASE: A 55-year-old male presented with
      left eye discomfort, diplopia and pulsatile tinnitus. He had a recent history of
      head injury. Examination showed proptosis, chemosis, orbital bruit, and abducens
      nerve palsy. Digital subtraction angiography confirmed CCF, which was managed
      endovascularly. The patient recovered fully after treatment. DISCUSSION: CCF has
      a variety of presenting clinical signs, imaging manifestations, and treatment
      options available. CONCLUSION: CCF is a rare and dangerous neurological disorder
      that should be promptly diagnosed and treated.

PMID- 23959421
TI  - An incidental and uncommon pulmonary sequestration with an uncommon feeding
      artery.
AB  - INTRODUCTION: Pulmonary sequestration is a rare congenital anomaly and most
      intralobar sequestrations were located in lower lobes. There is little
      information on middle lobe intralobar sequestration. PRESENTATION OF CASE: A 44
      year-old man with right middle lobe syndrome was referred for surgical
      management. He underwent video-assisted thoracoscopic right middle lobectomy and
      his postoperative course was uneventful. Pathology is notable for an incidental
      intralobar sequestration. DISCUSSION: Our case was unique in that the location of
      incidental pulmonary sequestration is uncommon and in that its feeding artery was
      uncommonly located in the fissure. CONCLUSION: We report an extremely rare case
      of right middle lobe intralobar sequestration with a feeding artery in the
      fissure.

PMID- 23959422
TI  - Evaluation of the Effect of NT-3 and Biodegradable Poly-L-lactic Acid Nanofiber
      Scaffolds on Differentiation of Rat Hair Follicle Stem Cells into Neural Cells In
      Vitro.
AB  - Recent improvement in neuroscience has led to new strategies in neural repair.
      Hair follicle stem cells are high promising source of accessible, active, and
      pluripotent adult stem cells. They have high affinity to differentiate to
      neurons. Aside from using cell-scaffold combinations for implantation, scaffolds
      can provide a suitable microenvironment for cell proliferation, migration, and
      differentiation. NT-3 is the most interesting neurotrophic factors being an
      important regulator of neural survival and differentiation. Since treatment
      duration in neural repair is very important, this study aims to evaluate the
      effect of NT-3 and poly-L-lactic acid (PLLA) on differentiation time of bulge
      stem cells of rat hair follicle to neural-like cells. HFSCs of rat whisker was
      isolated and cultured on PLLA and differentiated with 10 ng/mL NT-3. Biological
      features of cultured cells were evaluated with immunocytochemistry and
      flowcytometry methods by using CD34, nestin, and betaIII-tubulin markers. For
      cell viability and morphological assessment, MTT assay and SEM were performed.
      Our results showed that bulge stem cells of hair follicle can express CD34 and
      Nestin before differentiation. By using NT-3 during differentiation process, the
      cells showed positive reaction to betaIII-tubulin antibody. MTT results
      demonstrated that PLLA significantly increased cell viability. Finally, HFSCs
      adhesion was confirmed by SEM results. The results indicate that 10 ng/mL NT-3
      and PLLA have significant effect on differentiation time of rat HFSCs to neural
      cells even in 10 days.

PMID- 23959423
TI  - Wip1 phosphatase involved in lipopolysaccharide-induced neuroinflammation.
AB  - Wild type p53-induced phosphatase 1 (Wip1) is a phosphatase which belongs to
      protein phosphatase type 2C family, which have been predominantly linked to cell
      growth and to cellular stress signaling. Numerous downstream targets of Wip1 have
      been identified, and genetic studies confirm that some play a part in
      tumorigenesis. Recent evidence highlights a new role for Wip1 in the regulation
      of NF-kappaB p65, which indicated that it might play a critical role in immune
      system. However, its regulation role in central nervous system (CNS) remains
      poorly understood. To elaborate whether Wip1 was involved in CNS injury, we
      performed a neuroinflammatory model by lipopolysaccharide (LPS) lateral-ventral
      injection in adult rats.Wip1 expression was strongly upregulated in active
      astrocytes in inflamed brain cortex. In vitro studies indicated that the
      upregulation of Wip1 may be involved in the subsequent astrocytic activation
      following LPS exposure, and knockdown of Wip1 in primary astrocytes by siRNA
      showed that Wip1 inhibited the synthesis of TNF-alpha. Collectively, these
      results suggested that Wip1 may be important in host defense in CNS immune
      response, which might provide a potent therapeutic target of neuroinflammation.

PMID- 23959424
TI  - Upregulation of sestrin-2 expression via P53 protects against 1-methyl-4
      phenylpyridinium (MPP+) neurotoxicity.
AB  - Sestrin-2 (SESN2) is a conserved antioxidant protein that is activated upon
      oxidative stress and protects cells against reactive oxygen species (ROS).
      However, the role of SESN2 in neurodegenerative diseases, especially in
      Parkinson's disease (PD), has not yet been elucidated. In this study, we found
      that expression of SESN2 is elevated in the midbrain of patients with PD.
      Moreover, in vitro experiments display that the drug 1-methyl-4-phenylpyridinium
      (MPP+) induces the expression of SESN2 in SH-SY5Y cells in a time- and dose
      dependent manner. Our results show that p53 is activated by MPP+. Importantly,
      inhibition of p53 using small RNA interferences abolishes the increased SESN2
      levels induced by MPP+, suggesting that the inductive effect of MPP+ on SESN2 is
      mediated by p53. Furthermore, knockdown of SESN2 using small RNA interferences
      promotes MPP+-related neurotoxicity by attenuating oxidative stress,
      mitochondrial dysfunction, and apoptosis. All these data imply that the induction
      of SESN2 produces a protective effect in PD.

PMID- 23959425
TI  - CrkL efficiently mediates cell proliferation, migration, and invasion induced by
      TGF-beta pathway in glioblastoma.
AB  - Crk-like (CrkL) is an adapter protein that has crucial roles in cell
      proliferation, adhesion, and migration. However, the expression pattern and
      potential mechanism of CrkL protein in glioblastoma multiforme (GBM) have not
      been fully elucidated. To determine roles of CrkL in cell signaling,
      proliferation, and migration, small interfering RNAs and plasmids transfection
      were used to suppress or overexpress CrkL in U87 and U251; soft-agar assay and
      wound-healing assay were used to observe cell invasiveness, migration, and
      proliferation. Erk1/2, Smad2, and matrix metalloproteinase 9 (MMP9) were also
      analyzed by western blot. CrkL was expressed in U87 and U251 cell lines and can
      be activated by transforming growth factor-beta 1 (TGF-beta1) in vitro; CrkL
      knockdown significantly suppressed the expression of phosph-ERK1/2 and MMP9 but
      enhanced phosph-Smad2 expression compared with control (p <0.001). Overexpression
      of CrkL against control upregulated phosph-ERK1/2 and MMP9 and, at the same time,
      downregulated phosph-Smad2 (p <0.01). On the other hand, CrkL knockdown could
      significantly affect U87 and U251 invasiveness (p <0.01) and wound closure (p
      <0.01) using soft-agar assay and wound-healing assay. These studies suggest that
      CrkL efficiently mediates cell proliferation, migration, and invasion induced by
      TGF-beta pathway in glioblastoma. Furthermore, CrkL can be used as a potential
      and efficient therapeutic target of GBM and may also mediate other signaling
      pathway.

PMID- 23959426
TI  - A model of liver carcinogenesis originating from hepatic progenitor cells with
      accumulation of genetic alterations.
AB  - Activation-induced cytidine deaminase (AID) contributes to inflammation
      associated carcinogenesis through its mutagenic activity. In our study, by taking
      advantage of the ability of AID to induce genetic aberrations, we investigated
      whether liver cancer originates from hepatic stem/progenitor cells that
      accumulate stepwise genetic alterations. For this purpose, hepatic progenitor
      cells enriched from the fetal liver of AID transgenic (Tg) mice were transplanted
      into recipient "toxin-receptor mediated conditional cell knockout" (TRECK) mice,
      which have enhanced liver regeneration activity under the condition of diphtheria
      toxin treatment. Whole exome sequencing was used to determine the landscape of
      the accumulated genetic alterations in the transplanted progenitor cells during
      tumorigenesis. Liver tumors developed in 7 of 11 (63.6%) recipient TRECK mice
      receiving enriched hepatic progenitor cells from AID Tg mice, while no
      tumorigenesis was observed in TRECK mice receiving hepatic progenitor cells of
      wild-type mice. Histologic examination revealed that the tumors showed
      characteristics of hepatocellular carcinoma and partial features of
      cholangiocarcinoma with expression of the AID transgene. Whole exome sequencing
      revealed that several dozen genes acquired single nucleotide variants in tumor
      tissues originating from the transplanted hepatic progenitor cells of AID Tg
      mice. Microarray analyses revealed that the majority of the mutations (>80%) were
      present in actively transcribed genes in the liver-lineage cells. These findings
      provided the evidence suggesting that accumulation of genetic alterations in
      fetal hepatic progenitor cells progressed to liver cancers, and the selection of
      mutagenesis depends on active transcription in the liver-lineage cells. 

PMID- 23959427
TI  - Recurrence of autism spectrum disorders in full- and half-siblings and trends
      over time: a population-based cohort study.
AB  - IMPORTANCE: To date, this is the first population-based study to examine the
      recurrence risk for autism spectrum disorders (ASDs), including time trends, and
      the first study to consider the ASDs recurrence risk for full- and half-siblings.
      OBJECTIVES: To estimate the relative recurrence risk for ASDs in a Danish
      population, including recurrence in full- and half-siblings, and to examine time
      trends in ASDs relative to the recurrence risk. DESIGN, SETTING, AND
      PARTICIPANTS: Population-based cohort study in Denmark. All children (about 1.5
      million) born in Denmark between January 1, 1980, and December 31, 2004, were
      identified and followed up to December 31, 2010. We identified a maternal sibling
      subcohort derived from mothers with at least 2 children and a paternal sibling
      subcohort derived from fathers with at least 2 children. EXPOSURES: Children
      having an older sibling with ASDs are compared with children not having an older
      sibling with ASDs. MAIN OUTCOMES AND MEASURES: The adjusted hazard ratio for ASDs
      among children having an older sibling with ASDs compared with children not
      having an older sibling with ASDs. RESULTS The overall relative recurrence risk
      for ASDs was 6.9 (95% CI, 6.1-7.8), and it did not change significantly over
      time; similar risks were observed in maternal and paternal full-siblings. The
      relative recurrence risks were 2.4 (95% CI, 1.4-4.1) for maternal half-siblings
      and 1.5 (95% CI, 0.7-3.4) for paternal half-siblings. CONCLUSIONS AND RELEVANCE:
      Our population-based recurrence risk estimate is lower than the recently reported
      estimates from clinical samples. Our results demonstrate no time trend in the
      ASDs recurrence risk as seen in the ASDs prevalence. The difference in the
      recurrence risk between full- and half-siblings supports the role of genetics in
      ASDs, while the significant recurrence risk in maternal half-siblings may support
      the role of factors associated with pregnancy and the maternal intrauterine
      environment in ASDs.

PMID- 23959428
TI  - Stepwise versus pseudo-concerted two-electron-transfer in a triarylamine-iridium
      dipyrrin-naphthalene diimide triad.
AB  - A triad based on triarylamine donors, an iridium dipyrrin sensitiser and a
      naphthalene diimide acceptor is investigated using fs-pump-probe spectroscopy at
      two different pump wavelengths. Excitation of the naphthalene diimide induces a
      stepwise electron transfer process that yields within ca. 100 ps a charge
      separated state with 50-60% quantum yield in which one triarylamine is oxidised
      and the imide is reduced. Although being in the Marcus normal region, this state
      has a lifetime of 580 ns in MeCN. Excitation at the dipyrrin ligand centred
      absorption directly produces the charge separated state within ca. 1 ns however
      without formation of an intermediate. This pseudo-concerted two-electron transfer
      step was analysed with the help of a model dyad and a modified triad and is
      interpreted to be caused by inverted electron transfer rates. Although being much
      slower the latter process has a quantum yield of practically 100%. 

PMID- 23959429
TI  - Neural systems underlying reward and approach behaviors in childhood and
      adolescence.
AB  - Transitions into and out of adolescence are critical developmental periods of
      reward-seeking and approach behaviors. Converging evidence suggests that
      intriguing reward-related behavioral shifts are mediated by developmental changes
      in frontostriatal circuitry. This chapter explores how the conceptual frameworks
      and empirical studies in the field of developmental cognitive neuroscience have
      contributed to understanding reward-related behavior across development.The
      chapter concludes with some implications for adaptive and maladaptive behaviors
      that arise from these behaviors as children transition from childhood to
      adolescence.

PMID- 23959430
TI  - Spacer optimization of new conjugates for a melanoma-selective delivery approach.
AB  - In the search for more selective anticancer drugs, we designed and synthesized
      seven conjugates varying the structure of the linker connecting the 5-iodo-2'
      deoxyuridine (IUdR) to the ICF 01012 melanoma-carrier for potential intratumoural
      specific drug release. Chemical and in vitro metabolic stability evaluations
      showed that, except for the ester conjugate (1), the ketal (2b), acetal (2a),
      carbonate (4) and carbamate (3) conjugates were compatible with our approach. The
      acetal (2a) and its PEGylated derivative (2c) were of particular interest for
      further in vivo development owing to their respective pH-dependent stability and
      limited metabolic degradation in order to exploit the acidic subcellular
      environment of malignant melanocytes to trigger the release of therapeutics upon
      internalization in cells.

PMID- 23959431
TI  - Structural characterization of neutral glycosphingolipids using high-performance
      liquid chromatography-electrospray ionization mass spectrometry with a repeated
      high-speed polarity and MSn switching system.
AB  - Four types of neutral glycosphingolipids (LacCer, Gb3Cer, Gb4Cer, and
      IV3alphaGalNAc-Gb4Cer; 10 pmol each) were analyzed using high-performance liquid
      chromatography (HPLC)-electrospray ionization quadrupole ion trap time-of-flight
      (ESI-QIT-TOF) mass spectrometry (MS) with a repeated high-speed polarity and MSn
      switching system. This system can provide six types of mass spectra, including
      positive and negative ion MS, MS2, and MS3 spectra, within 1 s per cycle. Using
      HPLC with a normal-phase column, information on the molecular weights of major
      molecular species of four neutral glycosphingolipids was obtained by detecting
      [M+Na]+ in the positive ion mode mass spectra and [M-H]- in the negative ion mode
      mass spectra. Sequences of glycosphingolipid oligosaccharide were obtained in the
      negative ion MS2 spectra. In addition, information on the ceramide structures was
      clearly obtained in the negative ion MS3 mass spectra. GlcCer molecular species
      were analyzed by HPLC-ESI-QIT-TOF MS with a reversed-phase column using 1 pmole
      of GlcCer. The structures of the seven molecular species of GlcCer, namely, d18:1
      C16:0, d18:1-C18:0, d18:1-C20:0, d18:1-C22:0, d18:1-C23:0, d18:1-C24:1, and d18:1
      C24:0, were characterized using positive ion MS and negative ion MS, MS2, and
      MS3. The established HPLC-ESI-QIT-TOF MS with MSn switching and a normal phase
      column has been successfully applied to the structural characterization of LacCer
      and Gb4Cer in a crude mixture prepared from human erythrocytes.

PMID- 23959432
TI  - Laminin and collagen modulate expression of the small leucine-rich proteoglycan
      fibromodulin in rat anterior pituitary gland.
AB  - The anterior pituitary is a complex organ consisting of five types of hormone
      producing cells, non-hormone-producing cells such as folliculostellate (FS) cells
      and vascular cells (endothelial cells and pericytes). We have previously shown
      that FS cells and pericytes produce fibromodulin, a small leucine-rich
      proteoglycan (SLRP). SLRPs are major proteoglycans of the extracellular matrix
      (ECM) and are important in regulating cell signaling pathways and ECM assembly.
      However, the mechanism regulating fibromodulin expression in the anterior
      pituitary has not been elucidated. Here, we investigate whether fibromodulin
      expression is modulated by major anterior pituitary ECM components such as
      laminin and type I collagen. Using transgenic rats expressing green fluorescent
      protein (GFP) specifically in FS cells, we examine fibromodulin expression in GFP
      positive (FS cells) and GFP-negative cells (e.g., pericytes, endocrine cells and
      endothelial cells). Immunostaining and Western blot analysis were used to assess
      protein expression in the presence and absence of laminin or type I collagen. We
      confirmed fibromodulin expression in the pituitary and observed the up-regulation
      of fibromodulin in FS cells in the presence of ECM components. However, neither
      laminin nor type I collagen affected expression in GFP-negative cells. This
      suggests that laminin and type I collagen support the function of FS cells by
      increasing fibromodulin protein expression in the anterior pituitary.

PMID- 23959433
TI  - Assessment of knee function and biochemical parameters of articular fluid and
      peripheral blood in gonarthrosis patients following intra-articular
      administration of hyaluronic acid.
AB  - BACKGROUND: The development of gonarthrosis (GA) involves inflammatory processes;
      the role of reactive oxygen species (ROS) is being increasingly mentioned. The
      body is protected from oxidative damage by the antioxidative barrier with
      fundamental role being played by antioxidative enzymes, such as superoxide
      dismutase (SOD), catalase (CAT) and enzymes involved in glutathione
      transformations, particularly glutathione peroxidase (GPx). The methods of
      treatment of cartilage depend on the disease advancement, patient's reactions to
      pain, disease-related impairment in daily activities, as well as the age and
      overall health of the patient. Viscosupplementation involving intra-articular
      injection of agents that increase the viscosity of the articular fluid is aimed
      at reducing the friction between articular surfaces and thus at reducing pain and
      excessive wear of the remaining articular cartilage. The objective of the study
      was to examine whether intra-articular administration of a hyaluronic acid agent
      has any effect on the function of the knee and on the selected biochemical
      parameters of the articular fluid and blood in gonarthrosis, as well as to
      demonstrate of correlation or no correlation between the effects of
      viscosupplementation and administration of hyaluronic acid into a knee containing
      articular fluid or a "dry" knee. MATERIAL AND METHODS: The study group consisted
      of 22 gonarthrosis patients who received hyaluronic acid into the knee containing
      the articular fluid (group PS) as per the study protocol and 27 gonarthrosis
      patients who received hyaluronic acid into the "dry" knee (group PPI). The study
      lasted about 40 weeks and involved 10 visits at the study site. Hyaluronic acid
      was administered intra-articularly upon the first three visits held in one-week
      intervals, as well as on visit 4 (12 weeks after visit 3). The study knee was
      assessed clinically at all visits using the osteoarthritis WOMAC scale, visual
      assessment scale (0-10) for the assessment of pain intensity and HHS
      questionnaire for clinical assessment of the knee function. Blood for study
      related analyses was collected at study start and 12 weeks after administration
      of the third dose of hyaluronic acid. The activity of superoxide dismutase (SOD)
      within the articular fluid and plasma and plasma levels of MDA were determined.
      Results Worse WOMAC-scale quality of life was observed in patients with
      osteoarthrosis and "dry" knee, mostly due to higher joint stiffness. Following
      viscosupplementation treatment, improvement in all tested WOMAC scores was
      observed in both groups, and no significant differences between groups was
      observed. The SOD activity and the MDA levels in plasma did not differ between
      the study groups, both before the study and after viscosupplementation. No
      statistically significant changes were observed in the biochemical parameters
      following viscosupplementation in both groups other than for reduced articular
      fluid MDA levels in the PS group. CONCLUSIONS: Viscosupplementation with
      hyaluronic acid administration is an effective method of conservative treatment
      in patients with gonarthrosis. Its beneficial effect consists mostly of pain
      reduction and knee function improvement both in patients with articular fluid
      present within the knee joints as in patients with "dry" knee joints.

PMID- 23959434
TI  - Evaluation of the Simplexa Flu A/B and RSV test for the rapid detection of
      influenza viruses.
AB  - Recently, various molecular systems have been introduced for the detection of
      influenza viruses. Among these, the Simplexa Flu A/B and respiratory syncytial
      virus (RSV) test can provide results in approximately 2 hr. Nasopharyngeal swabs
      from 241 patients (influenza A, n = 81; influenza B, n = 80; influenza A and
      influenza B mixed, n = 1; influenza A and RSV A mixed, n = 2; and influenza and
      RSV negative, n = 77) were analyzed using the Simplexa Flu A/B and RSV test, a
      conventional reverse-transcription polymerase chain reaction (RT-PCR) assay, and
      a real-time RT-PCR assay. Compared to conventional RT-PCR, the Simplexa test had
      respective sensitivities and specificities of 100% and 100% for influenza A and
      100% and 99.4% for influenza B with extracted RNA samples, and 91.7% and 99.4%
      for influenza A, and 97.5% and 98.1% for influenza B with unprocessed patient
      specimens. All RSV A specimens were successfully detected by the Simplexa test
      using both extracted RNA samples and unprocessed patient specimens. The real-time
      RT-PCR assay had respective sensitivities and specificities of 96.4% and 99.4%
      for influenza A, and 98.8% and 99.4% for influenza B. The Simplexa test was
      effective at detecting influenza viruses from extracted RNA samples as well as
      from unprocessed patient specimens. The assay was not only simple and rapid for
      influenza detection, but the performance was also comparable to that of other
      conventional molecular methods.

PMID- 23959435
TI  - Low-temperature plasma synthesis of carbon nanotubes and graphene based materials
      and their fuel cell applications.
AB  - Carbon nanotubes (CNTs) and graphene, and materials based on these, are largely
      used in multidisciplinary fields. Many techniques have been put forward to
      synthesize them. Among all kinds of approaches, the low-temperature plasma
      approach is widely used due to its numerous advantages, such as highly
      distributed active species, reduced energy requirements, enhanced catalyst
      activation, shortened operation time and decreased environmental pollution. This
      tutorial review focuses on the recent development of plasma synthesis of CNTs and
      graphene based materials and their electrochemical application in fuel cells. 

PMID- 23959436
TI  - Early-stage diffuse large B cell lymphoma of the head and neck: clinico
      biological characterization and 18 year follow-up of 488 patients (IELSG 23
      study).
AB  - It is known that extranodal head and neck diffuse large B cell lymphomas (eHN
      DLBCL) can affect various anatomical structures what is not well-known, however,
      is whether they differ in terms of clinical presentation and outcome. Clinical
      data of the multi-institutional series, the largest of its kind as yet, has been
      analysed with the aim of answering these open questions and providing long-term
      follow-up information. Data from 488 patients affected by stage I/II eHN-DLBCL
      was collected: 300 of the Waldeyer's Ring (WR), 38 of the parotid and salivary
      glands (PSG), 48 of the thyroid gland (TG), 53 of the nasal cavity and paranasal
      sinuses (NPS), 24 of the palate and oral cavity (POC) and 25 with more than one
      involved site. Different eHN-DLBCL arising have distinct characteristics at
      presentation. The intermediate high risk-modified IPI was 67 % in TG, 44 % in WR,
      38 % in PSG and POC and 20 % in MS. The worst 5-year survival rate had TG-DLBCL
      (61 %) due to the 61 % of patients with a mIPI >1. The addition of radiotherapy
      (cRT) to remitters did not translate into a survival advantage (5-year disease
      free survival of 67 % in the cRT group vs. 70 % in the other). Three of four
      central nervous system recurrences occurred in NPS-DLBCL. Survival of HN-DLBCL
      was inferior to nodal DLBCL. This study showed that eHN-DLBCL remitters have an
      inferior survival when compared to nodal DLBCL, and that the addition of cRT does
      not provide a survival advantage. Since the standard of care nowadays is chemo
      immunotherapy, survival of these patients might have been improved.

PMID- 23959437
TI  - Association of polymorphisms in TRAIL1 and TRAILR1 genes with susceptibility to
      lymphomas.
AB  - The TRAILR1/TRAIL system is implicated in the induction of the extrinsic
      apoptotic pathway and constitutes an emerging target in cancer therapeutics. The
      objective of this study is to assess lymphoma risk associated with certain
      polymorphisms in TRAILR1 and TRAIL1 genes. DNA was extracted from 381 subjects
      (190 lymphoma cases and 191 matched controls) and genotyped for polymorphisms
      rs20576, rs2230229 and rs20575 in TRAILR1 and rs12488654 in TRAIL gene. In
      contrast to TRAILR1 polymorphisms, the genotype distribution of rs12488654 in
      TRAIL gene was different between cases and controls, A allele carriers (CA/AA)
      being much more common in the cases with different lymphoma types (follicular, 45
      %; diffuse large B cell, 45.2 % and Hodgkin lymphomas, 40 %) than in controls
      (15.7 %) (odds ratio (OR), 3.5; CI, 2.1-5.9; p<0.001; OR, 3.5; CI, 1.6-7.9;
      p=0.001; OR, 2.9; CI, 1.1-7.5; p=0.027, respectively). This effect was
      consistently independent of the association with the TRAILR1 polymorphisms
      studied, as demonstrated by linkage disequilibrium and haplotype analyses. This
      study is the first one to report an association between a TRAIL polymorphism and
      lymphoma risk and suggests a possible role of TRAIL in B cell lymphomagenesis.

PMID- 23959438
TI  - The reproducibility of cardiac and liver T2* measurement in thalassemia major
      using two different software packages.
AB  - In b-thalassemia major (TM) multiple blood transfusions are needed for survival.
      As a consequence these patients present iron overload in different organs,
      including heart and liver. Magnetic resonance imaging using a bright blood
      gradient echo sequence has been successfully used for the quantification of
      tissue iron. The aim is to evaluate of the accuracy and precision in the
      evaluation of liver and myocardial T2* values in TM using two different
      analytical software solutions. Thirty TM patients aged 20-56 years (mean age 37,
      11M/19F) were scanned in a GE 1.5 T CVI system. Each scan included the
      measurement of heart and liver T2* and the left ventricular ejection fraction
      using standard techniques. The analysis of T2* of heart and liver was done using
      the two different analytical software solutions: the "Functool" protocol by GE
      and the T2* module of QMassMR v7.4 by Medis medical imaging systems bv, Leiden,
      The Netherlands. The cardiac and liver T2* measurements showed that both software
      solutions allow reproducible measurements with low intra-observer variations
      (accuracy < 0.3 ms, precision < 2 ms). There is a small but significant
      difference between the two solutions of 2.4 ms in cardiac and of 1.5 ms in liver
      measurements. However, from the clinical point of view these differences (<2 ms)
      are small with negligible impact on the patient's treatment management. The
      comparison of the T2* measurements using the two analytical software solutions
      proved that both techniques enable reproducible measurements for the evaluation
      of iron overload in heart and liver.

PMID- 23959439
TI  - Microbial oxidation of dispersed graphite by nitrifying bacteria 2011.2.
AB  - A facile and green microbial method to produce graphite oxide nanosheets and
      nanoparticles is described. The obtained graphite oxide nanosheets have few
      layers with 0.7-1.5 nm height and 50-300 nm size. The carbon nanoparticles
      possess the size of 20-60 nm and the height of 2-4 nm. 

PMID- 23959442
TI  - A NEW FRAMEWORK FOR ANALYZING WHITE MATTER MATURATION IN EARLY BRAIN DEVELOPMENT.
AB  - The trajectory of early brain development is marked by rapid growth presented by
      volume but also by tissue property changes. Capturing regional characteristics of
      axonal structuring and myelination via neuroimaging requires analysis of
      longitudinal image data with multiple modalities. Complementary to earlier
      studies of volume and cortical folding analysis, this paper focuses on white
      matter tissue changes as seen in multimodal MRI and DTI. We propose a new
      framework for analyzing early maturation in white matter that generates a
      normative spatiotemporal model and provides 3D maps of absolute and relative
      indices of maturation. The method, using a continuous model of intensity changes
      using modified Legendre polynomials, has been applied to a multimodal dataset
      (T1W, T2W, PD, DTI) with 8 subjects that have been scanned at approximately 2
      weeks, 1 year, and 2 years. We demonstrate that spatial maturation maps generated
      from different modalities capture different properties of white matter growth
      which might lead to a better understanding of the underlying neurobiology.

PMID- 23959441
TI  - Mimicking of estradiol binding by flame retardants and their metabolites: a
      crystallographic analysis.
AB  - BACKGROUND: Brominated flame retardants (BFRs), used in many types of consumer
      goods, are being studied because of concerns about possible health effects
      related to endocrine disruption, immunotoxicity, reproductive toxicity, and
      neurotoxicity. Tetrabromobisphenol A (TBBPA), the most widely used BFR, and human
      metabolites of certain congeners of polybrominated diphenyl ether (e.g., 3-OH-BDE
      47) have been suggested to inhibit estrogen sulfotransferase, potentially
      affecting estrogen metabolism. OBJECTIVES: Our primary goal was to understand the
      structural mechanism for inhibition of the hormone-metabolizing enzyme estrogen
      sulfotransferase by certain BFRs. We also sought to understand various factors
      that facilitate the binding of flame retardants in the enzyme binding pocket.
      METHODS: We used X-ray crystallography to obtain atomic detail of the binding
      modes of TBBPA and 3-OH-BDE-47 to estrogen sulfotransferase for comparison with
      binding of the endogenous substrate estradiol. RESULTS: The crystal structures
      reveal how BFRs mimic estradiol binding as well as the various interactions
      between the compounds and protein residues that facilitate its binding. In
      addition, the structures provide insights into the ability of the
      sulfotransferase substrate binding pocket to accommodate a range of halogenated
      compounds that satisfy minimal structural criteria. CONCLUSIONS: Our results show
      how BFRs or their metabolites can bind to and inhibit a key hormone-metabolizing
      enzyme, potentially causing endocrine disruption.

PMID- 23959443
TI  - Myocardial reloading after extracorporeal membrane oxygenation alters substrate
      metabolism while promoting protein synthesis.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) unloads the heart,
      providing a bridge to recovery in children after myocardial stunning. ECMO also
      induces stress which can adversely affect the ability to reload or wean the heart
      from the circuit. Metabolic impairments induced by altered loading and/or stress
      conditions may impact weaning. However, cardiac substrate and amino acid
      requirements upon weaning are unknown. We assessed the hypothesis that
      ventricular reloading with ECMO modulates both substrate entry into the citric
      acid cycle (CAC) and myocardial protein synthesis. METHODS AND RESULTS: Sixteen
      immature piglets (7.8 to 15.6 kg) were separated into 2 groups based on
      ventricular loading status: 8-hour ECMO (UNLOAD) and postwean from ECMO (RELOAD).
      We infused into the coronary artery [2-(13)C]-pyruvate as an oxidative substrate
      and [(13)C6]-L-leucine as an indicator for amino acid oxidation and protein
      synthesis. Upon RELOAD, each functional parameter, which were decreased
      substantially by ECMO, recovered to near-baseline level with the exclusion of
      minimum dP/dt. Accordingly, myocardial oxygen consumption was also increased,
      indicating that overall mitochondrial metabolism was reestablished. At the
      metabolic level, when compared to UNLOAD, RELOAD altered the contribution of
      various substrates/pathways to tissue pyruvate formation, favoring exogenous
      pyruvate versus glycolysis, and acetyl-CoA formation, shifting away from pyruvate
      decarboxylation to endogenous substrate, presumably fatty acids. Furthermore,
      there was also a significant increase of tissue concentrations for all CAC
      intermediates (~80%), suggesting enhanced anaplerosis, and of fractional protein
      synthesis rates (>70%). CONCLUSIONS: RELOAD alters both cytosolic and
      mitochondrial energy substrate metabolism, while favoring leucine incorporation
      into protein synthesis rather than oxidation in the CAC. Improved understanding
      of factors governing these metabolic perturbations may serve as a basis for
      interventions and thereby improve success rate from weaning from ECMO.

PMID- 23959444
TI  - Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart
      failure: the potential role of nerve growth factor.
AB  - BACKGROUND: Autonomic imbalances including parasympathetic withdrawal and
      sympathetic overactivity are cardinal features of heart failure regardless of
      etiology; however, mechanisms underlying these imbalances remain unknown. Animal
      model studies of heart and visceral organ hypertrophy predict that nerve growth
      factor levels should be elevated in heart failure; whether this is so in human
      heart failure, though, remains unclear. We tested the hypotheses that neurons in
      cardiac ganglia are hypertrophied in human, canine, and rat heart failure and
      that nerve growth factor, which we hypothesize is elevated in the failing heart,
      contributes to this neuronal hypertrophy. METHODS AND RESULTS: Somal morphology
      of neurons from human (579.54+/-14.34 versus 327.45+/-9.17 MUm(2); P<0.01) and
      canine hearts (767.80+/-18.37 versus 650.23+/-9.84 MUm(2); P<0.01) failing
      secondary to ischemia and neurons from spontaneously hypertensive rat hearts
      (327.98+/-3.15 versus 271.29+/-2.79 MUm(2); P<0.01) failing secondary to
      hypertension reveal significant hypertrophy of neurons in cardiac ganglia
      compared with controls. Western blot analysis shows that nerve growth factor
      levels in the explanted, failing human heart are 250% greater than levels in
      healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth
      factor are significantly larger and have greater dendritic arborization than
      neurons in control cultures. CONCLUSIONS: Hypertrophied neurons are significantly
      less excitable than smaller ones; thus, hypertrophy of vagal postganglionic
      neurons in cardiac ganglia would help to explain the parasympathetic withdrawal
      that accompanies heart failure. Furthermore, our observations suggest that nerve
      growth factor, which is elevated in the failing human heart, causes hypertrophy
      of neurons in cardiac ganglia.

PMID- 23959445
TI  - Efficacy and safety of rituximab as maintenance therapy for relapsing
      granulomatosis with polyangiitis-a case series.
AB  - The objective of this work was to study the efficacy and safety of pre-emptive
      rituximab (RTX) in a series of patients with severe relapsing granulomatosis with
      polyangiitis (GPA). GPA is a systemic vasculitis with a high relapse rate despite
      successful remission induction. Drug toxicity with repeated induction treatments
      and long-standing immunosuppression poses a problem. Based on the findings in
      reports on RTX for rheumatoid arthritis, we treated patients with severe
      relapsing GPA with pre-emptive RTX, 1,000 mg 2 weeks apart every 6 months, aiming
      at achieving sustainable remission. All patients at one centre with relapsing GPA
      in spite of traditional maintenance treatment, who had received more than or
      equal to three cycles of RTX as regularly repeated pre-emptive maintenance
      therapy every 6 months, were included in this retrospective study. Information on
      disease manifestations and activity, treatments, lab parameters and adverse
      events was extracted from the medical files. Of the 12 included patients, all
      with a positive proteinase 3-anti-neutrophil cytoplasmic antibodies, generalised
      disease and a median disease duration of 35 months (21-270), 92% (11/12) achieved
      sustainable remission during a median follow-up time of 32 months (range 21-111)
      from first RTX treatment. Concomitant immunosuppressants were reduced. Infections
      were the most common adverse events, but infections were an issue also before the
      start of RTX. RTX administered every 6 months seems to be an effective
      maintenance treatment in a population with severe, relapsing long-standing GPA.
      Granulomatous as well as vasculitic manifestations responded equally well.
      Infections are a problem in this patient group but no new safety problems were
      identified.

PMID- 23959446
TI  - Severe inflammation may be caused by hyperferritinemia of pseudo-pseudo Meigs'
      syndrome in lupus patients: two cases reports and a literature review.
AB  - Pseudo-pseudo Meigs' syndrome or Tjalma syndrome is a rare manifestation of
      patients with systemic lupus erythematosus defined by the presence of ascites,
      pleural effusions, and an elevated cancer antigen 125 level. In this case, we
      described a patient with lupus who presented with sudden impaired renal function
      and subsequent development of massive ascites with marked high serum ferritin.
      Hyperferritinemia is one of the abnormal laboratory findings in severe
      inflammation with ferritin functioning as an inflammatory marker. However, its
      correlation with lupus activity remains unclear. Therefore, a review of the
      literature regarding pseudo-pseudo Meigs' syndrome associated with lupus and high
      ferritin level in this disease was carried out.

PMID- 23959447
TI  - Impact of 24-month treatment with etanercept, adalimumab, or methotrexate on
      metabolic syndrome components in a cohort of 210 psoriatic arthritis patients.
AB  - Psoriatic arthritis (PsA) is a chronic inflammatory condition, characterized by
      an excess of metabolic disorders. Metabolic syndrome (MetS) is a cluster of
      classic cardiovascular risk factors, due to an imbalance between pro- and anti
      inflammatory adipokines. Tumor necrosis factor (TNF)-alpha is a pro-inflammatory
      adipocytokine mainly produced by monocytes and macrophages with a central role in
      inflammatory responses, but it also induces adipocytes apoptosis, promotes
      insulin resistance, and stimulates lipolysis. The aim of this study was to
      evaluate the impact of therapy with etanercept (ETN), adalimumab (ADA), and
      methotrexate (MTX) on MetS components in a cohort of PsA patients with a follow
      up period of 24 months. A retrospective study has been conducted in a cohort of
      PsA patients. On the basis of the inclusion criteria, we identified the first 70
      consecutive patients, respectively, on ADA, ETN, and MTX, for a total of 210
      patients achieving PsARC criteria during the observation period. As part of the
      routine clinical practice, assessment of metabolic parameters and of disease
      activity was recorded at baseline (T0), at 12 months (T1), and at 24 months (T2).
      The results show that when the specific components of the MetS were considered,
      taking also into account by regression analysis the effect of the confounding
      factors, the patients on etN and ADA show a significant improvement of the
      metabolic syndrome components (in detail, waist circumference, triglycerides,
      high-density lipoprotein cholesterol, and glucose) as compared to the MTX group.
      In conclusion, these data suggest that the biologic treatment in PsA can no
      longer be taken into consideration only for its positive effect on articular and
      cutaneous symptoms but also on the various aspects of this complex picture.

PMID- 23959448
TI  - Functional nanoparticles obtained from cellulose: engineering the shape and size
      of 6-carboxycellulose.
AB  - Agricultural residue derived cellulose and cotton cellulose were used to
      synthesize quasi-spherical nanoparticles of 6-carboxycellulose having diameter 25
      35 nm. This provides a new range of functionalized nanostructured celluloses with
      increased versatility and applications. The nanoparticles were efficient in
      stabilizing carbon nanotube dispersions and were effective anti-microbial agents
      against E. coli. 

PMID- 23959449
TI  - Increased expression of TBX2 is a novel independent prognostic biomarker of a
      worse outcome in colorectal cancer patients after curative surgery and a
      potential therapeutic target.
AB  - T-box2 (TBX2) plays a critical role in embryonic development. Recently,
      deregulated expression of TBX2 has been implicated in several malignancies.
      However, the expression and the role of TBX2 in colorectal cancer (CRC) remain
      unclear. In this study, we found that TBX2 was obviously up-regulated in CRC in
      comparison with the corresponding normal mucosa at transcriptional and protein
      level. Up-expression of TBX2 was significantly associated with depth of tumor
      invasion (P = 0.006), distant metastasis (P = 0.038), advanced AJCC stage (P =
      0.008), and relapse (P = 0.003). TBX2 was a significantly prognostic factor for
      decreased survival and increased disease recurrence independent of tumor
      stage(II, III stage) and functioned as a biomarker to identify prognosis of
      patients with CRC (OS: HR 2.154; 95% CI 1.019-4.551; P = 0.044, DFS: HR 2.253;
      95% CI 1.109-4.575; P = 0.025). Furthermore, TBX2 could serve as a potential
      target of cancer drug therapy.

PMID- 23959450
TI  - High-dose methotrexate, high-dose cytarabine and temozolomide for the treatment
      of primary central nervous system lymphoma (PCNSL).
AB  - Treatment of primary central nervous system lymphoma (PCNSL) associates with low
      response rates and poor survival using conventional radio and chemotherapy. Due
      to its favorable toxicity profile, temozolomide has emerged as a new option for
      treatment of PCNSL in young patients. In this study, we report a series of PCNSL
      patients treated with an innovative regimen combining high dose of both
      cytarabine and methotrexate with temozolomide without radiotherapy or intrathecal
      chemotherapy. To evaluate a new intensive chemotherapy with temozolomide, trying
      to assess response and progression-free survival rates and if the results are
      promising, we are aiming at evaluating the overall survival (OS) taking into
      consideration the toxicity profile. The study was performed at Al Mowassa Charity
      Hospital in Damascus (Syria). Forty patients with histologically confirmed PCNSL
      median age 52 years (range 20-65) years were included. Biopsies were cultured,
      and a karyotyping was made in 32 patients. An induction chemotherapy was started,
      and methotrexate 3 gr/m2 over 12 h on day 1, cytarabine 3 gr/m2 every 12 h on day
      1 and temozolomide 150 mg/m2 from day 2 through day 6 with a total of 6 cycles
      were given on a monthly basis. Among the 40 patients included in the study, a
      complete response was observed in 34 patients (85%) and a partial response in the
      remaining 6 patients (15%). Disease progressed in 8 out of 40 patients (20%)
      while 32 patients are still living at 5 years making the OS reaching 77%. Grade
      II nephrotoxicity was observed in 2 patients while grade III and IV
      hematotoxicity was observed in 5 patients. High dose of both Ara-C and MTX
      combined with temozolomide appears to be a good choice in the treatment of PCNSL,
      in the light of good response and OS rates, taking into consideration the
      acceptable toxicity profile. However, a larger trial is needed to make it an
      acceptable new combination as a first line for PCNSL patients.

PMID- 23959452
TI  - Relationship between antithyroglobulin autoantibodies and thyroglobulin recovery
      rates using different thyroglobulin concentrations in the recovery buffer.
AB  - The aim of the work was to examine the relationship between thyroglobulin
      autoantibody (TgAb) levels and the Tg recovery rate (TgRR) using different
      concentrations of Tg (50, 10, 5, and 1 MUg/l) in the recovery buffer. A total
      number of 225 serum samples from individual patients were analyzed. Samples were
      selected for their TgAb in 6 groups: TgAb<limit of detection (LoD; n=50),
      LoD<TgAb<=60 IU/ml (n=62), 60 IU/ml<TgAb<=100 IU/ml (n=30), 100 IU/ml<TgAb<=500
      IU/ml (n=41), 500 IU/ml< TgAb<=1 000 IU/ml (n=13) and TgAb>1 000 IU/ml (n=28).
      TgAb were measured with 2 different assays (VARELISA and BRAHMS Anti-Tgn RIA).
      TgAb levels and the TgRR determined using the 50, 10, 5, and 1 ug/l buffers
      showed strong significant correlations with a Spearmans' rho of - 0.720, - 0.688,
      - 0.686, and - 0.356, respectively, for the VARELISA assay and - 0.670, -0.617, -
      0.570, and - 0.274, respectively, for the Anti-Tgn assay (all p<0.001). TgRRs
      were a median of 94.8% (30.5-113.0%), 90.8% (40.6-127.6%), 90.0% (8.2-119.3%),
      and 89.4% (range - 43.6-121.6%) for the TgRR determined using recovery buffers
      with concentrations of 50, 10, 5, and 1 MUg/l respectively. With decreasing Tg
      concentration in the recovery buffer the percentage of abnormal results
      increased, although the extreme increase we found in the 1 MUg/l group is largely
      caused by a lack of analytical precision in the 73 sera with Tg levels exceeding
      5 MUg/l. Our results give cause for further investigation into reviving the
      concept of Tg-recovery measurement using 5 MUg/l Tg in the recovery buffer
      instead of the traditional 50 MUg/l. 

PMID- 23959453
TI  - Comparison of silatrane, phosphonic acid, and carboxylic acid functional groups
      for attachment of porphyrin sensitizers to TiO2 in photoelectrochemical cells.
AB  - A tetra-arylporphyrin dye was functionalized with three different anchoring
      groups used to attach molecules to metal oxide surfaces. The physical,
      photophysical and electrochemical properties of the derivatized porphyrins were
      studied, and the dyes were then linked to mesoporous TiO2. The anchoring groups
      were beta-vinyl groups bearing either a carboxylate, a phosphonate or a siloxy
      moiety. The siloxy linkages were made by treatment of the metal oxide with a
      silatrane derivative of the porphyrin. The surface binding and lability of the
      anchored molecules were studied, and dye performance was compared in a dye
      sensitized solar cell (DSSC). Transient absorption spectroscopy was used to study
      charge recombination processes. At comparable surface concentration, the
      porphyrin showed comparable performance in the DSSC, regardless of the linker.
      However, the total surface coverage achievable with the carboxylate was about
      twice that obtainable with the other two linkers, and this led to higher current
      densities for the carboxylate DSSC. On the other hand, the carboxylate-linked
      dyes were readily leached from the metal oxide surface under alkaline conditions.
      The phosphonates were considerably less labile, and the siloxy-linked porphyrins
      were most resistant to leaching from the surface. The use of silatrane proved to
      be a practical and convenient way to introduce the siloxy linkages, which can
      confer greatly increased stability on dye-sensitized electrodes with
      photoelectrochemical performance comparable to that of the other linkers. 

PMID- 23959454
TI  - The future possibilities of diagnostic testing for the evaluation of febrile
      infants.

PMID- 23959455
TI  - DABCO-promoted synthesis of pyrazoles from tosylhydrazones and nitroalkenes.
AB  - An efficient synthesis of pyrazoles from tosylhydrazones and nitroalkenes was
      developed. In comparison with the previously reported 1,3-dipolar cycloaddition
      reaction of diazo compounds with electron-deficient alkenes or alkynes, this
      methodology proceeded with a sequential Baylis-Hillman/intramolecular cyclization
      mechanism and a variety of reversed regioselectivity products were prepared in
      good yields. 

PMID- 23959457
TI  - [National second-opinion network for testicular cancer patients. Results of a
      user survey].
AB  - BACKGROUND: The national second opinion project of the German Testicular Cancer
      Study Group (GTCSG) has served to improve the quality of care provided to
      testicular cancer patients since 2006. AIM: A recent online survey was carried
      out to characterize the users of the second opinion offer and clarify their
      motivation for participating in the project. Furthermore, the aim was to identify
      weaknesses of the project which could be improved. A total of 440 users of the
      second opinion project were contacted of whom 192 participated in the survey.
      RESULTS: In summary, the data collected showed a high degree of satisfaction
      among the participants who appreciated the second opinions received. Some issues
      with a need for improvement, predominantly in the structural organisational area,
      were disclosed. These served as a basis for a recently completed revision of the
      project immanent internet-based communication platform with a new data mask
      facilitating the introduction of patients with relapsed tumors. Interestingly, a
      high proportion of survey participants expressed the desire for establishment of
      a similar second opinion project for patients with penile cancer (77.1% of the
      participants).

PMID- 23959456
TI  - Dysphagia associated with cervical spine and postural disorders.
AB  - Difficulties with swallowing may be both persistent and life threatening for the
      majority of those who experience it irrespective of age, gender, and race. The
      purpose of this review is to define oropharyngeal dysphagia and describe its
      relationship to cervical spine disorders and postural disturbances due to either
      congenital or acquired disorders. The etiology and diagnosis of dysphagia are
      analyzed, focusing on cervical spine pathology associated with dysphagia as
      severe cervical spine disorders and postural disturbances largely have been held
      accountable for deglutition disorders. Scoliosis, kyphosis-lordosis, and
      osteophytes are the primary focus of this review in an attempt to elucidate the
      link between cervical spine disorders and dysphagia. It is important for
      physicians to be knowledgeable about what triggers oropharyngeal dysphagia in
      cases of cervical spine and postural disorders. Moreover, the optimum treatment
      for dysphagia, including the use of therapeutic maneuvers during deglutition,
      neck exercises, and surgical treatment, is discussed.

PMID- 23959458
TI  - [Urological surgery with analogosedation and local anesthesia. What makes
      sense?].
AB  - OBJECTIVE: Analogosedation and local anesthesia, including regional nerve blocks
      are used for endoscopic diagnostic or radiological and ultrasound-guided
      procedures in which the patient should not move or has to be free of pain. We
      retrospectively analyzed patient satisfaction, complications and the risk of
      urological interventions with analgosedation and/or local anesthesia between 2008
      and 2012. MATERIAL AND METHODS: In total 21,690 urological patients underwent
      surgical treatment at the Department of Urology of the University Hospital of
      Essen between 2008 and 2012 and 3,327 of these cases were performed by urologists
      with the patient under analogosedation (n=1484) and local anesthesia (n=1843). In
      total 13 surgical and endoscopic procedures were separately analyzed and
      evaluated for safety and practicability. RESULTS: In five cases (0.15%) the
      procedures with analgosedation or local anesthesia were interrupted because of
      agitation (n=3) and in one case the transurethal resection was stopped due to a
      large bladder tumor. One patient suffered anaphylactic shock after preoperative
      intravenous application of cefuroxim 1.5 g. After cardiopulmonary resuscitation
      and a short stay on the intensive care unit the patient was discharged after 2
      days.Conclusions. Local anesthesia and analgosedation should be performed by
      urologists for minor surgery, endoscopic procedures and radiological or
      ultrasound-guided treatment. For safety reasons there should always be a second
      medical doctor present for assistance. Analgesia with deep sedation or loss of
      defensive reflexes should be administered by anesthesiologists.

PMID- 23959459
TI  - Bevacizumab confers additional advantage to the combination of trastuzumab plus
      pertuzumab in trastuzumab-refractory breast cancer model.
AB  - PURPOSE: We investigated antitumor activity of trastuzumab (T)/T-DM1 + pertuzumab
      (P) + bevacizumab (B) in T-sensitive (BT474) and T-resistant (BT474HerR) BC
      models in order to test whether or not the addition of an anti-angiogenic drug
      can provide a supplementary advantage to the antitumor activity of double HER2
      mAB combination. METHODS: In addition to the antitumor activity (xenograft
      model), we tested antiproliferative effect, and HER2-mediated signals of
      different antibodies (T or P or T-DM1) in HER2-amplified T-sensitive, T-resistant
      and HER2-amplified/PIK3CA mutated (HCC1954) BT cell lines by 3D ON-TOP clonogenic
      growth assay and Western blots. RESULTS: Data show (1) T, T-DM1 or P blocked p
      AKT (>60 %), p-ERK (>50 %) following heregulin in only T-sensitive cells, (2) T/T
      DM1 + P, T/T-DM1 + B, and P + B reduced tumor growth as compared to any single
      agent treatment, (3) T + P + B achieved almost complete regression of tumor
      growth, decreased cell proliferation, and inhibited tumor-induced angiogenesis,
      in both models, (4) antitumor activity of T + P + B was associated with the
      pharmacodynamic knockdown of p-AKT, and (5) T-DM1 + P caused complete regression
      of tumor volume in both models. CONCLUSIONS: Our data demonstrate that B imparts
      a significant advantage when combined with T + P in the resistant model, in
      contrast to T-DM1 + P, as the triple combination of T-DM1 + P + B and the double
      combination of T-DM1 + P showed a comparable antitumor activity. Our study
      reveals the preclinical evidence in favor of the inclusion of B when combined
      with T + P in T-resistant BC patients.

PMID- 23959460
TI  - Effects of pemetrexed, gefitinib, and their combination on human colorectal
      cancer cells.
AB  - PURPOSE: The study investigated the effects of pemetrexed, gefitinib, and their
      combination on human colorectal cancer cells. METHODS: Six human colorectal
      cancer cells were exposed to pemetrexed, gefitinib, and their combination.
      Antitumor effects were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. Thymidylate synthase (TS) mRNA expression and
      EGFR mutation were studied by real-time RT-PCR and DNA sequence determination.
      Pharmacological interaction was studied using the combination index method. Cell
      cycle distribution and apoptosis were determined by flow cytometry. Activity
      assay was performed to assess the effects of drugs on TS activity, and Western
      blot was performed to assess the protein expression of pEGFR, pAKT, and pERK 1/2.
      RESULTS: Six colorectal cancer cells are all sensitive to pemetrexed, and TS gene
      expression of cells was negatively related to pemetrexed sensitivity. The
      cytotoxic synergism was observed in concurrent pemetrexed combined with gefitinib
      and sequential pemetrexed followed by gefitinib. The combination of pemetrexed
      and gefitinib modulated cell cycle and induced apoptosis. Pemetrexed combined
      with gefitinib decreased TS mRNA expression and in situ activity. Pemetrexed
      induced an EGFR-mediated activation of the phosphatidylinositol 3-kinase/AKT and
      ERK pathway, which was inhibited by gefitinib. CONCLUSIONS: Pemetrexed is a
      promising agent, and pemetrexed combined with gefitinib has a significantly
      synergistic effect on colorectal cancer cells, which seems to present a strategy
      of pemetrexed combined with EGFR-TKIs in colorectal cancer treatment.

PMID- 23959461
TI  - Receptor tyrosine kinase alterations and therapeutic opportunities in squamous
      cell carcinoma of the lung.
AB  - PURPOSE: Targeted therapy has greatly improved the treatment for adenocarcinoma
      of the lung, but not squamous cell carcinoma (SCC) of the lung. The current paper
      describes the abnormalities of receptor tyrosine kinases (RTK) in lung SCC in a
      hope to stimulate the development of therapeutics that can have clinical impact.
      METHODS: We reviewed both clinical and preclinical studies published in English
      regarding RTK abnormalities and/ or RTK-targeting treatment for SCC of the lung.
      RESULTS: RTK alterations have been demonstrated as biological signature for SCC
      of the lung. A number of clinical trials of RTK-targeting therapy have been
      carried out or are ongoing, with encouraging results. CONCLUSIONS: SCC of the
      lung should be treated as an independent disease with unique treatment options
      based on molecular changes, particularly RTK.

PMID- 23959463
TI  - Treatment results and prognostic factors for advanced squamous cell carcinoma of
      the larynx treated with concurrent chemoradiotherapy.
AB  - OBJECTIVE: To review our experience with concurrent chemoradiotherapy (CCRT) for
      patients with advanced resectable squamous cell carcinoma (SCC) of the larynx and
      to evaluate the factors affecting survival and larynx preservation. STUDY DESIGN:
      Retrospective study. SUBJECTS AND METHODS: The records of 102 patients with stage
      III or IV resectable SCC of the larynx treated with CCRT between February 1994
      and March 2009 were reviewed. Of 102 patients, 59 were treated with high-dose
      regimens, including cisplatin, 5-fluorouracil (5-FU), methotrexate, and
      leucovorin or docetaxel, cisplatin, and 5-FU, and 43 were treated with low-dose
      regimens, including carboplatin and uracil-tegafur or S-1. Radiotherapy was
      delivered 5 days a week using a single daily fraction of 1.8-2.0 Gray (Gy), to a
      total dose of 66.0-70.2 Gy. Overall survival (OS), disease-specific survival
      (DSS), and DSS with larynx preservation were estimated using Kaplan-Meier
      methods. The log-rank test and Cox proportional hazards regression were used to
      identify significant prognostic factors for DSS and DSS with larynx preservation.
      RESULTS: The 5-year OS and DSS for all patients treated with CCRT were 63.9 and
      70.7 %, respectively. The 5-year DSS with larynx preservation was 54.1 %. On
      multivariate analysis, N stage, synchronous multiple primary cancers, and the
      contents of chemotherapy were significant predictors of OS for patients
      undergoing CCRT; T stage, N stage, and the contents of chemotherapy were
      significant prognostic factors for larynx preservation. CONCLUSION: The treatment
      method including the indication for CCRT may be determined by the contents of the
      chemotherapy and the T and N stages of laryngeal SCC. It is important to diagnose
      multiple synchronous primary cancers before CCRT.

PMID- 23959462
TI  - The role of antioxidants in the era of cardio-oncology.
AB  - Although most chemotherapeutic drugs have the potential to exert cardiotoxicity,
      these drugs have been chosen for use in cancer treatment because survival and
      curability benefits outweigh the risk of these complications. Anthracyclines, for
      example, are a powerful class of chemotherapeutic agents; however, their use is
      restricted by dose-related cardiotoxicity. Experimental evidence strongly
      supports the role of reactive oxygen species in this process, suggesting that
      antioxidants may be effective in protecting the heart from toxicity. Clinical use
      of antioxidants to protect the heart during anthracycline chemotherapy has been
      controversial due to the potential for reduced cytotoxic efficacy toward cancer
      cells. Results from randomized clinical trials addressing whether antioxidants
      either reduce the incidence of clinical heart failure among patients undergoing
      anthracycline-based chemotherapy or reduce the response rates to anthracycline
      based chemotherapy have been unclear. While anthracyclines are by far the most
      well-studied antitumor agents with cardiotoxic properties, evidence now shows
      that reactive oxygen species may play roles in cardiotoxicity induced by other
      chemotherapeutic agents such as cyclophosphamide, cisplatin, 5-fluorouracil, and
      trastuzumab. Thus, in the new era of combination therapy and long-term survival
      of cancer patients, the use of antioxidants to support cancer therapy should be
      revisited.

PMID- 23959465
TI  - UV-assisted nucleation and growth of oxide films from chemical solutions.
AB  - The fabrication of thin oxide films at low temperatures using simple processes
      has been a significant challenge associated with expanding the potential
      applications of these materials. Recent developments have demonstrated that the
      photo-assisted chemical solution deposition (PACSD) process offers a promising
      means of solving these difficulties, allowing high volume, on-demand production
      of variable sample sizes using an advantageous wet process. A better
      understanding of the crystal growth phenomena associated with this process,
      however, is required to enable various oxide thin films to be prepared using this
      new concept. Under pulsed ultraviolet (UV) laser irradiation, crystal growth has
      been confirmed to proceed by near-instantaneous photothermal heating and
      photochemical effects at the reaction interface. Vacuum UV lamp irradiation is
      also a useful means of generating oxide nuclei, since it results in effective
      chemical bond cleavage and simultaneously produces reactive oxidant (O3/O((1)D))
      species. In this review, the nucleation and growth mechanisms which occur during
      the PACSD process are introduced and discussed and we examine the future possible
      applications of this process. 

PMID- 23959464
TI  - Reversibility of regorafenib effects in hepatocellular carcinoma cells.
AB  - PURPOSE: Multikinase growth inhibitors inhibit their target kinases with varying
      potency. Patients often require lower doses or therapy breaks due to drug
      toxicities. To evaluate the effects of drug withdrawal on hepatocellular
      carcinoma cells after incubation with growth-inhibitory concentrations of
      regorafenib, cell growth, migration and invasion, and signaling were examined.
      METHODS: Cell proliferation, motility, and invasion were analyzed by MTT, wound
      healing, and invasion assays, respectively, and MAPK pathway protein markers were
      analyzed by Western blot. RESULTS: After regorafenib removal, cell growth,
      migration, and invasion recovered. Repeated drug exposure resulted in changes in
      cell growth patterns. Recovery could be blocked by sub-growth-inhibitory
      concentrations of either doxorubicin or vitamin K1. Recovery of growth was
      associated with increased phospho-JNK, phospho-p38, and phospho-STAT3 levels. The
      recovery of growth, migration, and signaling were blocked by a JNK inhibitor.
      CONCLUSIONS: Removal of regorafenib from growth-inhibited cells resulted in a JNK
      dependent recovery of growth and migration.

PMID- 23959466
TI  - Appetitive and aversive olfactory learning induce similar generalization rates in
      the honey bee.
AB  - Appetitive and aversive learning drive an animal toward or away from stimuli
      predicting reinforcement, respectively. The specificity of these memories may
      vary due to differences in cost-benefit relationships associated with appetitive
      and aversive contexts. As a consequence, generalization performances may differ
      after appetitive and aversive training. Here, we determined whether honey bees
      show different rates of olfactory generalization following appetitive olfactory
      conditioning of the proboscis extension response, or aversive olfactory
      conditioning of the sting extension response. In both cases, we performed
      differential conditioning, which improves discrimination learning between a
      reinforced odor (CS?) and a non-reinforced odor (CS-) and evaluated
      generalization to two novel odors whose similarity to the CS? and the CS- was
      different. We show, given the same level of discriminatory performance, that
      rates of generalization are similar between the two conditioning protocols and
      discuss the possible causes for this phenomenon.

PMID- 23959467
TI  - The pure shape effect with a removing facet effect of single-crystalline anatase
      TiO2 (101) for photocatalytic application.
AB  - 3D TiO2 nanobipyramids (TiO2-NPs) and 1D TiO2 nanobelts (TiO2-NBs) were
      synthesized from potassium titanate K2Ti6O13 and characterized by X-ray
      diffraction (XRD) patterns, field emission scanning electron microscopy (FESEM),
      transmission electron microscopy (TEM), high-resolution transmission electron
      microscopy (HRTEM), selected area electron diffraction (SAED) patterns and fast
      Fourier transform (FFT). The as-synthesized 3D TiO2 nanobipyramids and 1D TiO2
      nanobelts all show high {101} facet exposed percentages and were used to
      investigate the shape effect of TiO2 with the same facet exposure. 3D TiO2
      nanobipyramids (101) showed higher photocatalytic activity than 1D TiO2 nanobelts
      (101). The reasons were discussed using ROS (reactive oxygen species) production,
      time-resolved photoluminescence spectra, XPS (X-ray photoelectron spectroscopy)
      spectra and ATR-IR (attenuated total reflectance infrared spectroscopy) spectra.
      The postulated mechanism suggests that 3D TiO2 nanobipyramids have more step
      edges which results in more -OH/H2O molecule adsorption and longer life times of
      photoinduced carriers than 1D TiO2 nanobelts.

PMID- 23959468
TI  - GSTT1 null genotype contributes to hepatocellular carcinoma risk: a meta
      analysis.
AB  - Studies investigating the association between genetic polymorphism of glutathione
      S-transferase T1 (GSTT1) and hepatocellular carcinoma (HCC) risk have reported
      conflicting results. Therefore, we conducted this meta-analysis to provide more
      precise evidence. Databases including PubMed, Embase, SCOPUS, ISI Web of Science,
      and Wangfang were searched for relevant studies. Potential sources of
      heterogeneity were also assessed by subgroup analysis. Funnel plots and Egger's
      linear regression were used to test publication bias among the articles. Finally,
      a total of 28 studies involving 3,897 HCC patients and 6,117 controls were
      included in this meta-analysis. In a combined analysis, the summary odds ratio
      for HCC of the GSTT1 null genotype was 1.43 (95% confidence interval (CI) 1.22
      1.68, P < 10(-5)). In the subgroup analysis by ethnicity, significantly increased
      risks were found in East Asians for GSTT1 null polymorphism, while no significant
      associations were found among Caucasian, South Asian, and African populations.
      When stratified by a source of controls, both population- and hospital-based
      studies get consistent positive results. By pooling data from 10 studies (1,639
      cases and 2,224 controls) that considered combinations of GSTT1 and GSTM1
      genotypes, a statistically significant increased risk for HCC (odd ratio = 1.85,
      95% CI 1.37-2.49) was detected for individuals with combined deletion mutations
      in both genes compared with positive genotypes. No evidence of publication bias
      was observed. Our result suggests that the GSTT1 null genotype contributes to an
      increased risk of HCC in East Asians and that interaction between unfavorable
      GSTs genotypes may exist.

PMID- 23959469
TI  - Bibliometric analysis of nanotechnology applied in oncology from 2002 to 2011.
AB  - Innovation in the last decade has endowed nanotechnology with an assortment of
      tools for drug delivery system, imaging, and sensing in cancer research. These
      rapidly emerging tools are indicative of a burgeoning field ready to expand into
      medical applications. The aim of this study is to analyze the applications of
      nanotechnology in oncology with bibliometric methods and evaluate development in
      this field. Literature search was performed using PubMed search engines with MeSH
      terms (all)--nanotechnology, nanomedicine, nanoparticle, nanocapsules, micellar
      systems, and oncology or cancer or neoplasms. Within 2,543 articles from 2002 to
      2011 in over 50 medical magazines from over 30 countries, we did a series
      analysis on these articles' countries, keywords, and authors. Our results show
      that articles in nanotechnology in oncology are increasing year by year,
      especially in recent years. Quantity and quality of the articles are becoming
      more and influential. In the global research, the USA is leading in this field,
      accounting for half above of the whole articles, followed by countries like
      Japan, Germany, and France and also some emerging nations like China, in the
      second place, and India. Subjects like nanoparticles, tumor marker, and drug
      delivery are the common research focus. So, with more and more scientists'
      interests and attention drawn to this field, it is likely to make major
      breakthroughs in the coming years.

PMID- 23959470
TI  - Rosiglitazone and imidapril alone or in combination alleviate muscle and adipose
      depletion in a murine cancer cachexia model.
AB  - Rosiglitazone (RGZ) and imidapril improve cancer cachexia via different
      mechanisms. Therefore, we hypothesized that combination therapy of RGZ+imidapril
      would further attenuate cancer cachexia in vivo. After injection with colon-26
      adenocarcinoma for 9 days, BALB/c mice were randomly divided into the following
      four treatment groups for 7 days (n = 8 per group): (1) placebo, (2) RGZ, (3)
      imidapril, and (4) RGZ+imidapril. Eight healthy control animals were also
      assessed. Body weight, tumor volume, gastrocnemius muscle and epididymal adipose
      mass, serum metabolic markers and cytokines, and the expression of nuclear factor
      kappaB and two E3 ubiquitin ligases, atrogin-1 and MuRF-1, were measured. From
      days 14 to 16, all treatments significantly reduced tumor volume (P < 0.05). From
      days 10 to 16, improvements in the tumor-free body weight were observed in the
      RGZ and RGZ+imidapril groups. In addition, significant improvements in both
      gastrocnemius muscle and epididymal adipose mass were observed in all treatment
      groups (all, P < 0.05). Furthermore, all treatments significantly increased tumor
      necrosis factor alpha levels as compared to those observed in the healthy control
      animals (P < 0.001). Insulin levels significantly increased in the placebo group
      as compared to those in the healthy control group (P < 0.05), which were reduced
      in all the treatment groups (P < 0.05). Finally, whereas all treatments
      significantly reduced atrogin-1 levels as compared to the placebo group (all, P <
      0.05), significant reductions in MuRF-1 levels were only observed in the RGZ and
      RGZ+imidapril groups (both, P < 0.05). Thus, all three treatments reduce tumor
      growth and alleviate cancer cachexia; however, synergistic effects of
      RGZ+imidapril combination therapy were not observed.

PMID- 23959471
TI  - TR1 promotes cell proliferation and inhibits apoptosis through cyclin A and CTGF
      regulation in non-small cell lung cancer.
AB  - The Hippo pathway plays a major role in development and organ size control, and
      its dysregulation contributes to tumorigenesis. WWTR1 is a transcription
      coactivator acting downstream of the Hippo pathway. Recently, WWTR1 has been
      reported to be overexpressed in several human cancers including lung cancer.
      However, the molecular mechanism of WWTR1 regulating lung cancer aggressiveness
      remains ambiguous. In the present study, we analyzed the expression of WWTR1 in
      NSCLC cell lines and found that WWTR1 was overexpressed at both the mRNA and
      protein levels. Knockdown of WWTR1 by siRNA interference in A549 cells
      significantly inhibited cell proliferation and increased paclitaxel-induced
      apoptosis. On the other side, WWTR1 overexpression in HBE cell line promoted cell
      proliferation and inhibited apoptosis. In addition, we found that the decreased
      proliferation after siRNA treatment was due to cell cycle arrest. Further
      analysis showed that WWTR1 could induce cyclin A, connective tissue growth factor
      (CTGF) expression, and inhibit caspase3 cleavage. In conclusion, WWTR1 promotes
      malignant cell growth and inhibits apoptosis by cyclin A and CTGF regulation.

PMID- 23959472
TI  - Prognostic role of cytovillin expression in patients with osteosarcoma: a meta
      analysis.
AB  - Cytovillin plays structural and regulatory roles in the assembly and
      stabilization of specialized plasma membrane domains and in the tumor
      angiogenesis. Cytovillin expression has been proposed to be an effective
      biomarker of prognosis in patients with osteosarcoma, and many studies have been
      performed to assess the prognostic role of cytovillin expression in patients with
      osteosarcoma. We performed this meta-analysis to provide a comprehensive
      evaluation of the role of cytovillin expression on the overall survival rate by
      calculating the pooled risk ratio (RR) with corresponding 95% confidence interval
      (95% CI). Finally, eight studies with a total of 415 patients with osteosarcoma
      were included into the meta-analysis. Meta-analysis of total eight studies showed
      that cytovillin expression was obviously associated with lower overall survival
      rate in patients with osteosarcoma (RR = 0.41, 95% CI 0.28-0.58, P < 0.001). Meta
      analysis of five studies with large sample still showed that cytovillin
      expression was obviously associated with lower overall survival rate (RR = 0.48,
      95% CI 0.38-0.60, P < 0.001). In conclusion, the meta-analysis shows that
      cytovillin expression is obviously associated with lower overall survival rate in
      patients with osteosarcoma, and it is an effective biomarker of prognosis.

PMID- 23959473
TI  - Lost miRNA surveillance of Notch, IGFR pathway--road to sarcomagenesis.
AB  - The goal of this study was to compare and analyze differentially expressed miRNA
      and their targets in human chondrosarcoma JJ012 and chondrocytes C 28 cell lines
      (control) to elucidate deregulation of major signal transduction pathways
      involved in sarcomagenesis. Total RNA extraction was followed by analyzing RNA
      quality and integrity. Exiqon human miRNA panel of 743 unique miRNA assays and
      Illumina microarray HT-12 platform and quantitative reverse transcriptase-PCR
      verification of targets were performed. The results from human miRNA Exiqon
      arrays with biological triplicates indicated 28 significant miRNAs (P value
      <=0.01). A total 3,045 target genes were derived from the miRWalk database for
      these 28 miRNAs with 587 common and 2,458 unique target genes. The results of our
      analyses of the significantly downregulated and upregulated miRNAs in
      chondrosarcoma cell line indicated the predominant dysregulation of NOTCH,
      insulin-like growth factor receptor (IGFR), and downstream rat sarcoma, and Src
      pathways, compared to control. Among the upregulated targets for upregulated
      miRNAs were the cluster of cancer testis antigen (CTA) genes, located on X
      chromosome, and their expression was correlated to IGFR pathway activity. Based
      on our observations, lost miRNA surveillance of NOTCH and IGFR pathways is
      involved in and leads to sarcomagenesis. We conclude that upregulation of CTA
      genes is due to hypomethylation that are controlled by epi-miRNAs. We do not
      preclude the possibility that the upregulated miRNAs, which target CTA genes
      located in adjacent regions in chromosome X, are epi-miRNAs that influence target
      gene expression by directly regulating epigenetic processes. Future endeavors
      will be directed towards understanding the posttranscriptional modifications that
      affect miRNA expression in sarcomas.

PMID- 23959474
TI  - DNA polymerase beta mutations and survival of patients with esophageal squamous
      cell carcinoma in Linzhou City, China.
AB  - Linzhou City in northern China has a high incidence of esophageal squamous cell
      carcinoma (ESCC). This study retrospectively analyzed the data of 231 cases with
      ESCC collected from 1998 to 2012. Mutations of DNA polymerase beta (polbeta) gene
      in the ESCC samples from patients in Linzhou City were examined by amplifying
      polbeta cDNA by RT-PCR followed by cloning and sequencing. Mutations in polbeta
      were found in 105 cases (45.9%). Nine types of mutations were identified in the
      polbeta cDNA; the most common were 177-234 nt deletion (11.3%), 462 nt G -> T
      (9.1%), and 648 nt G -> C (6.9%). Mutations in polbeta appeared to be associated
      with TNM status (P = 0.048). Follow-up data was used for survival analysis. The
      overall 5-year survival rate of the 231 patients was 37.4%; the rate for patients
      with wild-type (WT) polbeta was 41.8%. Compared with the WT polbeta group, the
      median survival for patients with specific mutations (177-234 nt deletion, 462 nt
      G -> T, or 613 nt A -> T) was significantly shorter (all P = 0.000), and the 5
      year survival rate decreased to 0%. Patients with the 648 nt G -> C mutation had
      improved survival (P = 0.000) with a 5-year survival rate of 100%. Our results
      identified nine types of mutations within polbeta cDNA in ESCC patients with four
      mutations related to patient survival.

PMID- 23959475
TI  - Association of Kaposi's sarcoma-associated herpesvirus (KSHV) with bladder cancer
      in Croatian patients.
AB  - As the seventh most common human malignancy, bladder cancer represents a global
      health problem. In addition to well-recognized risk factors such as smoking and
      exposure to chemicals, various infectious agents have been implicated as
      cofactors in the pathogenesis of urothelial malignancies. The aim of the present
      study was to assess the possible association of viral infection and bladder
      cancer in Croatian patients. Biopsy specimens were collected from a total of 55
      patients diagnosed with different stages of bladder cancer. Initial screening of
      DNA extracts for the presence of viruses on Lawrence Livermore Microbial
      Detection Array revealed Kaposi's sarcoma-associated herpesvirus (KSHV) in each
      of three randomly chosen biopsy specimens. The prevalence of infection with KSHV
      among study population was then examined by KSHV-specific polymerase chain
      reaction (PCR) and immunoblotting. By nested PCR, KSHV DNA was detected in 55% of
      patients. KSHV, also known as human herpesvirus 8, is an infectious agent known
      to cause cancer. Its oncogenic potential is primarily recognized from its role in
      Kaposi's sarcoma, but it has also been involved in pathogenesis of two
      lymphoproliferative disorders. A high prevalence of KSHV infection in our study
      indicates that KSHV may play a role in tumorigenesis of bladder cancer and
      warrants further studies.

PMID- 23959476
TI  - Clinical characteristics and prognostic factors of prostate cancer with liver
      metastases.
AB  - Liver metastasis from prostate cancer is uncommon and remains poorly understood.
      We computer searched the clinical records of all our patients registered into a
      database to identify patients that presented or developed liver metastases. A
      total of 27 prostate cancer patients with ultrasound or CT/MR imaging evidence of
      liver metastases were included in our analysis. The liver metastasis rate from
      metastatic prostate cancer was 4.29%. Eight (29.63%) patients had previously
      untreated, hormone-naive prostate cancer (synchronous liver metastases at
      diagnosis of prostate cancer), whereas 19 (70.37%) patients had already been
      diagnosed as having hormone-refractory prostate cancer. In the hormone-naive
      group, the median overall survival after liver metastases diagnosis was 38 months
      and half of the patients were still alive at the latest follow-up, whereas only 6
      months in the hormone-refractory group (p = 0.003). High concentration of serum
      neuron-specific enolase and previous chemotherapy were associated with a
      significantly poor overall survival after liver metastases in the hormone
      refractory group using Kaplan-Meier curves and logrank tests for univariate
      analysis.

PMID- 23959477
TI  - Venous thromboembolism risk and erythropoiesis-stimulating agents for the
      treatment of cancer-associated anemia: a meta-analysis.
AB  - Erythropoiesis-stimulating agents (ESAs) reduce anemia in patients with cancer
      and could improve their quality of life, but ESA-related safety concerns exist.
      To evaluate the overall risk of venous thromboembolism (VTE) associated with the
      use of ESAs, a systematic review and meta-analysis of published randomized
      controlled trials (RCTs) was performed. The databases of PubMed and Web of
      Science and the abstracts presented at the American Society of Clinical Oncology
      conferences were searched to identify relevant clinical trials. Summary incidence
      rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated.
      A total of 12,115 patients with a variety of cancer types from 51 RCTs were
      identified and included in the meta-analysis. Among patients receiving ESAs, the
      summary incidence of all-grade VTE was 7.78%. Patients with cancer who received
      ESAs had increased VTE risks (484 events among 6,301 patients treated with ESA
      vs. 276 events among 5,814 control patients; RR = 1.75 [95% CI, 1.50-2.05]). The
      highest risk of VTE was found in patients with ovarian and cervical cancers (RR =
      2.45 [CI = 1.12-5.33]). The VTE risk among hematologic malignancies was higher
      than that among solid tumors. The administration of ESAs was significantly
      associated with an increased risk of developing VTE in cancer patients receiving
      these drugs. The risks of VTE may vary with various tumor types, including
      hematologic malignancies.

PMID- 23959478
TI  - Upregulation of miR-136 in human non-small cell lung cancer cells promotes Erk1/2
      activation by targeting PPP2R2A.
AB  - MicroRNAs (miRNAs) have been integrated into cancer development and progression,
      because they repress translation of target genes which can be tumor suppressors
      and oncogenes. A number of miRNAs have been found to be closely related to human
      non-small cell lung cancer (NSCLC). However, the roles of miR-136 in NSCLC are
      still largely unknown. Here, we show that miR-136 is significantly upregulated in
      human NSCLC primary tumors and cell lines compared to their nontumor
      counterparts. Suppression of miR-136 expression in NSCLC cell line A549 inhibited
      both anchorage-dependent and anchorage-independent proliferation. Further studies
      showed that suppression of miR-136 expression attenuated phosphorylation of
      extracellular-signal-regulated kinase 1/2 (Erk1/2). We found that
      serine/threonine protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform
      (PPP2R2A, also known as B55alpha) was a direct target of miR-136, and suppression
      of miR-136 expression led to a robust increase in both mRNA and protein levels of
      PPP2R2A. We found that miR-136 promoted phosphorylation of Erk1/2 through
      inhibition of PPP2R2A expression, and forced overexpression of PPP2R2A abrogated
      promotion of Erk1/2 phosphorylation by miR-136. Moreover, forced overexpression
      of PPP2R2A abrogated the promoting effect of miR-136 on cell growth and led to a
      reduced growth rate of NSCLC cells. Our findings indicate that miR-136 promotes
      Erk1/2 phosphorylation through targeting PPP2R2A in NSCLC cells and suggest that
      it may serve as a therapeutic target in NSCLC therapy.

PMID- 23959479
TI  - Quantitative assessment of the influence of common variations on 6p21 and lung
      cancer risk.
AB  - Genome-wide association studies have identified 6p21 as a new lung cancer
      susceptibility locus in populations of European descent. Since then, the
      relationship between common variations on 6p21 and lung cancer has been reported
      in various ethnic groups; however, these studies have yielded inconsistent
      results. To investigate this inconsistency, we performed a meta-analysis of 11
      studies involving a total of 36,890 cases and 52,767 controls for three widely
      studies polymorphisms (rs4324798, rs3117582, and rs9295740) to evaluate its
      effect on genetic susceptibility for lung cancer. An overall random-effects per
      allele odds ratio (OR) of 1.11 (95% confidence interval (CI) 1.04-1.19; P =
      0.002) and 1.20 (95% CI 1.14-1.26; P < 10(-5)) was found for the rs4324798 and
      rs3117582 polymorphism, respectively. Marginal significant associations were also
      detected for rs9295740 with per-allele OR of 1.09 (95% CI 1.01-1.18; P = 0.03).
      In the subgroup analysis by ethnicity, significantly increased risks were found
      for the three polymorphisms among Caucasians. Similar results were also observed
      using dominant or recessive genetic models. This meta-analysis demonstrated that
      the three common variations (rs4324798, rs3117582, and rs9295740) on 6p21 are
      risk factors associated with increased lung cancer susceptibility, but these
      associations vary in different ethnic populations.

PMID- 23959480
TI  - Curcumin induces osteosarcoma MG63 cells apoptosis via ROS/Cyto-C/Caspase-3
      pathway.
AB  - The antitumor effects of curcumin have attracted widespread attention worldwide.
      One of its major functions is to induce the apoptosis of tumor cells, but the
      antitumor mechanism is currently unclear. In the present study, we found that
      cell mortality and curcumin concentration were dose dependent. Curcumin of low
      concentrations (10 MUMU) could reduce the level of reactive oxygen species (ROS)
      in tumor cells, while curcumin of high concentrations (80 MUMU) was able to
      significantly increase the content of ROS. In addition, Western blotting
      detection suggested that curcumin of high concentrations can induce the release
      of Cyto-C and the activation of Caspase-3, and that ROS scavenger NAC apparently
      inhibits apoptosis protein release and activation, consequently slowing the
      curcumin-induced apoptosis. Taken together, curcumin further activates the
      mitochondrial apoptotic pathway by inducing cells to generate ROS and ultimately
      promotes the apoptosis of tumor cells.

PMID- 23959481
TI  - Mini review on chemotherapy of taeniasis and cysticercosis due to Taenia solium
      in Asia, and a case report with 20 tapeworms in China.
AB  - A 43-year-old Tibetan woman living in northwest Sichuan, China, confirmed to be a
      taeniasis carrier of Taenia solium was treated with pumpkin seeds combined with
      Areca nut extract in October 2009. All 20 tapeworms except one without scolex
      were expelled under good conditions. She was free of secondary cysticercosis
      within one year follow up. Although the first choice for treatment of taeniasis
      is still praziquantel, it may often cause serious side effect on asymptomatic
      cysticercosis cases to suddenly become symptomatic within a half day of the
      treatment. Therefore, the problems in treatment of taeniasis and/or cysticercosis
      in Asia are briefly overviewed, since other platyhelminthic diseases including
      schistosomiasis, opisthorchiasis etc. are more common and praziquantel is
      strongly recommended for mass treatment of these trematodiases with no idea on
      the co-infection with eggs of T. solium which cause asymptomatic cysticercosis. 

PMID- 23959482
TI  - Parasarcophaga (Liopygia) ruficornis (Diptera:Sarcophagidae): a flesh fly species
      of medical importance.
AB  - Parasarcophaga (Liopygia) ruficornis is a well-known flesh fly species of medical
      importance, both as a myiasis-producing agent and fly seen in a forensic
      entomology context. This study performed a comprehensive literature review of
      this fly species, dealing with morphology, bionomics and medical involvement.
      Important characteristics used to identify P. ruficornis have been provided for
      both its third instar and adult for identification purpose in the future. 

PMID- 23959483
TI  - Heterologous expression of uncharacterized parasitic nematode-specific growth
      factor-like protein of Setaria digitata in Pichia pastoris expression systems.
AB  - Setaria digitata is an animal filarial parasite infecting cattle and other
      ungulates causing mild to severe diseases, and infection of human by this
      nematode has also been reported. Therefore, this study was undertaken as an
      initial step towards the characterization of an uncharacterized gene of S.
      digitata, that encode for parasitic nematode-specific growth factor-like protein
      to which Wucheraria bancrofti and other filarial and parasitic nematodes have
      homologous counterparts (revealed by bioinformatic analyses), by means of protein
      expression and purification in Pichia pastoris. In Pichia expression system, S.
      digitata uncharacterized protein (SDUP) was expressed both as secretory and
      intracellular protein. SDS-PAGE and western blot analyses revealed expression of
      recombinant SDUP in P. pastoris, showing a band of 23.8 kDa, which is similar to
      theoretical molecular weight and also this protein was shown to be more
      concentrated into insoluble fraction than soluble fraction of cell lysates
      suggesting that the protein to be more hydrophobic than hydrophilic. Recombinant
      SDUP was successfully purified using Ni-NTA affinity chromatography purification
      technique and three dimensional structural studies of the purified protein are
      currently being progressed. This is the first report of the expression of S.
      digitata protein in P. pastoris. 

PMID- 23959484
TI  - Study on Cryptosporidium contamination in vegetable farms around Tehran.
AB  - In recent years, an increase in the number of cases of food-borne illnesses
      linked to fresh vegetables has been reported. One of the causative agents of
      these infections is Cryptosporidium and it appears that one route of transmission
      to humans is food-borne, so fruits and vegetables have important roles. The goal
      of this study was to determine the level of Cryptosporidium contamination in
      vegetable farms around Tehran, Iran. A total of 496 samples from 115 vegetable
      farms in different regions around Tehran (Capital city of Iran) were collected
      and different types of vegetables were investigated for the parasite in June and
      July, 2012. A sediment concentration method followed by modified Ziehl-Neelsen's
      acid-fast staining was used to determine the presence of Cryptosporidium oocysts.
      Our findings revealed that 6.6% of studied samples were contaminated with
      Cryptosporidium species. The highest rate of contamination was reported in Bagher
      Abad (South of Tehran) (11.1%), and green onions were more commonly contaminated
      (14.8%) than any other vegetables tested. Furthermore, when waste water was used
      to irrigate vegetable farms, the contamination rate was (33.3%). Statistical
      analysis showed a correlation between contamination with Cryptosporidium spp. and
      studied risk factors including: different regions around Tehran, type of
      vegetables, and type of water used for farm irrigation. Therefore, vegetables may
      provide a route by which Cryptosporidium can be transmitted to humans, and
      control strategies should be considered. 

PMID- 23959485
TI  - Biodiversity and macroparasitic distribution of the wild rat population of Carey
      Island, Klang.
AB  - A study to determine the diversity and distribution of ectoparasites and
      endoparasites infesting wild rat population of Carey Island was carried out from
      June to December 2010. A total of 81 rats were captured from various locations on
      Carey Island. Four rat species were identified namely, Rattus tiomanicus (45.7%),
      Rattus rattus diardii (25.9%), Rattus argentiventer (16%) and Rattus norvegicus
      (12.3%). Low diversity of ecto and endoparasites were observed infecting the
      rodent population with 8 ecto and 8 endoparasites species recorded. The
      ectoparasites recovered fell under 3 broad groups, namely mites (Laelaps nuttali,
      Laelaps echidninus, Laelaps sculpturatus, Listrophoroides sp. and Ornithonyssus
      bacoti), lice (Polyplax spinulosa and Hoplopleura pacifica) and tick (Ixodes
      granulatus) while endoparasites recovered were cestodes (Taenia taeniaformis and
      Hymenolepis diminuta) and nematodes (Nippostrongylus brasiliensis,
      Angiostrongylus malaysiensis, Mastophorus muris, Heterakis spumosa, Hepatojarakus
      malayae and Syphacia muris). The rat population was observed harbouring more than
      one parasite species. Analysis of data also showed neither intrinsic (host age,
      host sex) nor extrinsic (season) factors influenced the macroparasites community
      structure. 

PMID- 23959486
TI  - Molecular identification of Malaysian Chrysomya megacephala (Fabricius) and
      Chrysomya rufifacies (Macquart) using life stage specific mitochondrial DNA.
AB  - DNA identification of blow fly species can be a very useful tool in forensic
      entomology. One of the potential benefits that mitochondrial DNA (mtDNA) has
      offered in the field of forensic entomology is species determination.
      Conventional identification methods have limitations for sibling and closely
      related species of blow fly and stage and quality of the specimen used. This
      could be overcome by DNA-based identification methods using mitochondrial DNA
      which does not demand intact or undamaged specimens. Mitochondrial DNA is usually
      isolated from whole blow fly and legs. Alternate sources for mitochondrial DNA
      isolation namely, egg, larva, puparium and empty puparium were explored in this
      study. The sequence of DNA obtained for each sample for every life cycle stage
      was 100% identical for a particular species, indicating that the egg, 1st instar,
      2nd instar, 3rd instar, pupa, empty puparium and adult from the same species and
      obtained from same generation will exhibit similar DNA sequences. The present
      study also highlighted the usefulness of collecting all life cycle stages of blow
      fly during crime scene investigation with proper preservation and subsequent
      molecular analysis. Molecular identification provides a strong basis for species
      identification and will prove an invaluable contribution to forensic entomology
      as an investigative tool in Malaysia. 

PMID- 23959487
TI  - Temephos resistance in field Aedes (Stegomyia) albopictus (Skuse) from Selangor,
      Malaysia.
AB  - Larvae of Aedes albopictus obtained from dengue endemic areas in Selangor,
      Malaysia were evaluated for their susceptibility to operational dosage of
      temephos (1 mg/L). Larval bioassays were carried out in accordance to modified
      WHO standard methods. Biochemical microassay of enzymes in Ae. albopictus was
      conducted to detect the emergence of insecticide resistance and to define the
      mechanisms involved in temephos resistance. The 50% mortality lethal time (LT50)
      for Ae. albopictus tested against temephos ranged between 58.65 to 112.50
      minutes, with resistance ratio ranging from 0.75 - 1.45. This study addressed the
      fluctuation of time-related susceptibility status of Ae. albopictus towards
      insecticide. Significant difference on the weekly enzyme levels of non-specific
      esterases, mixed function oxidases and glutathione S-transferases was detected (p
      <= 0.05). No significant correlation was found between temephos resistance and
      enzyme activity (p > 0.05). Only glutathione S-transferases displayed high level
      of activity, indicating that Ae. albopictus may be resistant to other groups of
      insecticide. The insensitive acetylcholinesterase was detected in some field
      collected Ae. albopictus populations, indicating the possibility of emergence of
      carbamate or other organophosphate resistance in the field populations.
      Continuous resistance monitoring should be conducted regularly to confirm the
      efficacy of insecticides for dengue control. 

PMID- 23959488
TI  - Acaricidal effect of Cassia fistula Linn. leaf ethanolic extract against
      Rhipicephlaus (Boophilus) annulatus.
AB  - The present study evaluates the acaricidal properties of crude ethanolic extract
      of Cassia fistula leaves for controlling Rhipicephalus (Boophilus) annulatus
      based on adult immersion test (AIT). The percentage of adult mortality,
      inhibition of fecundity and hatching of ova laid were studied at different
      concentrations of the extract ranging from 50 to 100 mg / ml. The results were
      compared using one-way ANOVA. The extract produced complete inhibition of
      hatching of eggs at concentrations above 80 mg / ml of the extract. Mortality of
      adult engorged female ticks and inhibition of fecundity were concentration
      dependent. The LC50 value of extract against R. (B.) annulatus was 97.1 mg / ml. 

PMID- 23959489
TI  - Metaphase karyotypes of Anopheles paraliae (Diptera:Culicidae) in Thailand and
      evidence to support five cytological races.
AB  - Sixteen isoline colonies of Anopheles paraliae were established from wild-caught
      females collected from cow-baited traps at 4 locations in Thailand. They showed 3
      types of X (X1, X2, X3) and 5 types of Y (Y1, Y2, Y3, Y4, Y5) chromosomes based
      on the number and amount of major block(s) of heterochromatin present in the
      heterochromatic arm, and were designated as Forms A (X3, Y1), B (X1, X2, X3, Y2),
      C (X3, Y3), D (X1, X2, X3, Y4) and E (X3, Y5). Form A was found in Songkhla
      Province, Form B was obtained in Ratchaburi, Nakhon Si Thammarat and Songkhla
      Provinces, Form C was acquired in Chanthaburi Province, Form D was recovered in
      Ratchaburi and Songkhla Provinces, and Form E was encountered in Ratchaburi
      Province. Hybridization experiments among the 7 isoline colonies, which
      represented the 5 karyotypic forms of An. paraliae, revealed genetic
      compatibility in providing viable progenies and synaptic salivary gland polytene
      chromosomes through F2-generations, and thus suggest the conspecific nature of
      these karyotypic forms. These results were supported by the very low
      intraspecific sequence divergence (mean genetic distance = 0.000-0.002) of the
      nucleotide sequences in ribosomal DNA (ITS2) and mitochondrial DNA (COI and COII)
      of the 5 forms. 

PMID- 23959490
TI  - Efficacies of two in-house indirect ELISAs for diagnosis of amoebic liver
      abscess.
AB  - Entamoeba histolytica causes amoebic diarrhoea, colitis and liver abscess (ALA).
      Diagnosis of ALA is difficult, as most patients do not have simultaneous
      intestinal amoebic infection. At Hospital Universiti Sains Malaysia (HUSM),
      diagnosis of ALA relies on a combination of clinical findings, ultrasound
      examination of the liver and serodiagnosis using a commercial kit. In this study,
      two in-house indirect ELISAs were developed and evaluated. One of the in-house
      assays utilises E. histolytica crude soluble antigen (CSA) to detect serum IgG
      specific to the parasite whereas the other uses E. histolytica ether extract
      antigen (EEA). Preparation of CSA requires a sonicator to lyse the amoeba whereas
      EEA was prepared by chemically solubilizing the trophozoites. Based on the cut
      off value of mean optical density + 3SD, CSA-ELISA showed 100% (24/24)
      sensitivity and 93.33% (210/225) specificity; while EEA-ELISA showed 91.67%
      (22/24) sensitivity and 95.11% (214/225) specificity. In conclusion, both the in
      house indirect ELISAs were found to be efficacious for diagnosis of ALA; and the
      EEA is easier to prepare than the commonly used CSA. 

PMID- 23959491
TI  - Protein expression in sera of patients with amoebic liver abscess (ALA):
      potential use of haptoglobin as a surrogate disease marker.
AB  - The protein profile of serum samples from patients with amoebic liver abscess
      (ALA) was compared to those of normal individuals to determine their expression
      levels and to identify potential surrogate disease markers. Serum samples were
      resolved by two dimensional electrophoresis (2-DE) followed by image analysis.
      The up and down-regulated protein spots were excised from the gels and analysed
      by MS/MS. The concentration of three clusters of proteins i.e. haptoglobin (HP),
      alpha1-antitrypsin (AAT) and transferrin in serum samples of ALA patients and
      healthy controls were compared using competitive ELISA. In addition, serum
      concentrations of HP and transferrin in samples of patients with ALA and pyogenic
      liver abscess (PLA) were also compared. The results of the protein 2-DE
      expression analysis showed that HP cluster, AAT cluster, one spot each from
      unknown spots no. 1 and 2 were significantly up-regulated and transferrin cluster
      was significantly down-regulated in ALA patients' sera (p<0.05). The MS/MS
      analysis identified the unknown protein spot no.1 as human transcript and
      haptoglobin and spot no. 2 as albumin. Competitive ELISA which compared
      concentrations of selected proteins in sera of ALA and healthy controls verified
      the up-regulated expression (p<0.05) of HP and the down-regulated expression
      (p<0.01) of transferrin in the former, while there was no significant difference
      in AAT expression (p> 0.05). However, when ALA and PLA samples were compared,
      competitive ELISA showed significant increased concentration of HP (p<0.05) while
      transferrin levels were not different. In conclusion, this study showed that HP
      is a potential surrogate disease marker for ALA. 

PMID- 23959492
TI  - Epidemiological characteristics of malaria in Ningbo City, China 2000-2011.
AB  - The objective of this study was to explore the trend and the epidemiological
      characteristics of malaria in Ningbo from 2000 through 2011 and provide
      scientific evidence for the prevention and control. Using the retrospective
      study, data relating to malaria epidemics during 2000-2011 in Ningbo were
      collected through the questionnaires of the cases and other important
      surveillance data. Adult mosquitoes were collected using CDC light traps baited
      with CO2. Results showed that Plasmodium vivax was the main species, and
      Anopheles sinensis was the only vector species of malaria. The annual incidence
      rates (per 100000) ranged from 0.156 to 3.224, and about 95.41% of the cases were
      imported. The cases occurred mainly between May and November and the incidence
      showed two peaks, and the local transmission of malaria was determined by vector
      density. Considering the vast majority of these infections were imported vivax
      malaria cases from domestic endemic areas (particularly Anhui province), and may
      lead to limited local transmission, strengthening the routine monitoring of
      imported malaria, ensuring timely diagnosis, improving case detection rate,
      giving a standardized treatment to patients and intensifying public health
      education on malaria prevention are extremely important to malaria prevention and
      control activities. 

PMID- 23959493
TI  - Serologic detection of antibodies to Brucella spp. using a commercial ELISA in
      cattle in Grenada, West Indies.
AB  - Bovine brucellosis, caused mainly by Brucella abortus, a zoonotic bacterium, has
      been reported from many areas of the world, including Central and South America,
      and the Caribbean island state of Trinidad and Tobago. Although brucellosis has
      been eradicated from domestic cattle in Canada it still exists in one or two
      herds in the United States. Serological tests are important in estimating
      prevalence of Brucella exposure in order to target eradication programmes. In
      this study, serum samples from 150 cattle were tested using a commercial
      competitive enzyme linked immunosorbent assay (SVANOVIR(r)Brucella-Ab C-ELISA)
      which detects antibodies to both B. abortus and Brucella melitensis. All cattle
      tested were greater than 6 months old and were unvaccinated. Sampled cattle were
      from 35 herds representing animals from all 6 parishes of Grenada. Nine of the
      150 animals (6%) were positive for antibodies to B. abortus and/or melitensis by
      the C-ELISA. Of the 35 herds, 7 (20%) had C-ELISA- positive animals. Three of the
      6 parishes contained positive herds. Based on the high sensitivity (98%) and
      specificity (99.7%) of the C-ELISA, these results strongly indicate the presence
      of cattle exposed to B. abortus and/or melitensis in Grenada. 

PMID- 23959494
TI  - Phylogenetic analysis of bovine Theileria spp. isolated in south India.
AB  - The objective of the present study is to determine the phylogenetic position of
      the Theileria organisms in blood of cattle of southern India using molecular
      tools. Theileria annulata (Namakkal isolate, Tamil Nadu) and three Theileria
      field isolates (free of T. annulata) from Wayanad, Kerala (Wayanad 1, 2, 3) were
      used. The small subunit ribosomal RNA (SSU rRNA) and major piroplasm surface
      protein (MPSP) gene products were cloned, sequenced and the phylogenetic tree
      constructed. SSU rRNA gene of Wayanad 1 isolate (JQ706077) revealed maximum
      identity with Theileria velifera or Theileria cervi. The phylogenetic tree
      constructed based on SSU rRNA genes revealed that Wayanad 1 isolate belonged to a
      new type which share common ancestor with all the other theilerial species while
      Wayanad 2 and 3 isolates (JX294459, JX294460) were close to types A and C
      respectively. Based on MPSP gene sequences, Wayanad 2 and 3 (JQ706078, JX648208)
      isolates belonged to Type 1 and 3 (Chitose) respectively. When, the previously
      reported MPSP type 7 is also considered from the same study area, Theileria
      orientalis types 1, 3 and 7 are observed in south India. SSU rRNA sequence of
      South Indian T. annulata (JX294461) showed a maximum identity with Asian isolates
      while the Tams1 merozoite surface antigen (MSA) gene (JX648210) showed maximum
      identity with north Indian isolate. 

PMID- 23959495
TI  - Metabolite extract of Streptomyces hygroscopicus Hygroscopicus inhibit the growth
      of Plasmodium berghei through inhibition of ubiquitin - proteasome system.
AB  - Streptomyces hygroscopicus Hygroscopicus, a member of family of Actinomycetes
      produces eponemycin a proteasome inhibitor that can inhibit Ubiquitin-Proteasome
      System (UPS) function in eukaryotic cell. Previous study showed that coronamycin,
      an active substrate isolated from Streptomyces sp. can act as anti-plasmodial,
      antibacterial, and antifungal, however the research did not show the mechanism of
      coronamycin in inhibiting the growth of Plasmodium. This research was done to
      reveal if eponemycin that is contained in metabolite extract of S. hygroscopicus
      can inhibit UPS function of Plasmodium berghei. This study was an experimental
      study using P. berghei infected Balb/C mice as malaria model. Samples were
      divided into 1 control group (group infected with P. berghei without treatment)
      and 3 treatment groups (mice infected with P. berghei and treated intra
      peritoneal with metabolite extract of S. hygroscopicus dose 130 MUg/kgBW, 580
      MUg/kgBW, and 2600 MUg/kgBW for 5 days). The degree of parasitemia and morphology
      of the parasite were measured from the first day of malaria induction until the
      last treatment. The accumulation level of polyubiquitin was measured using
      Western blot and ELISA method. The degree of parasitemia on day 6 showed
      significant differences among treatment groups and control (p=0,000). Percentage
      of inhibition showed significant differences between control and group treated
      with metabolite extract of S. hygroscopicus 2600 MUg/kgBW. An increasing dose of
      extract of S. hygroscopicus followed by an increasing of inhibition in parasite
      growth (r=0,850). Probit analysis showed that ED50 was 9.418 MUg/kgBW. There was
      a change in morphology of the parasite after treatment. Parasite morphology
      became crisis form. There was an accumulation of polyubiquitinated protein in the
      group treated with metabolite extract of S. hygroscopicus 2600 MUg/kgBW. It can
      be concluded that analog eponemycin in metabolite of S. hygroscopicus is a
      potential candidate for new malarial drug by inhibiting UPS function of the
      parasite and cause stress and dead of the parasite. 

PMID- 23959496
TI  - Life table characteristics of Aedes aegypti (Diptera:Culicidae) from Saudi
      Arabia.
AB  - Aedes aegypti (= Stegomyia aegypti) mosquito is a world vector of important
      arboviral diseases like dengue and Rift Valley fever. Despite its wide
      distribution in the western and southern regions of Saudi Arabia, where dengue
      outbreaks have occurred, its ecology is largely unknown. In this study we report
      on the main life table developmental attributes of a laboratory colony of Ae.
      aegypti reared from field-collected larvae from Madinah Province, west of Saudi
      Arabia. Females were maintained on daily blood meal and sugar. The female
      fecundity was ~62 eggs/female at an overall rate of 72% hatchability. The mean
      time needed for eggs to hatch into larvae was 4.5 d. The mean pupation time (P50)
      was 11.53 days (d). The proportion of immature survivorships were 0.69 for 1(st)
      larva to pupa (P/I), 0.98 for pupa to adult (A/P) and an overall 0.67 for 1(st)
      larva to adult (A/I). Males emerged faster than females with mean emergence time
      (E50) of 12.83 and 15.31 d, respectively. The average developmental velocity (V)
      showed that males (V= 0.081) developed faster than females (V= 0.068). The
      male/female sex ratio at adult emergence was 0.48, and insignificantly different
      from the 1:1 ratio. The adult mean life expectancy at emergence (eo) was 17.14 d
      for females compared to 9.59 d for males. The net reproductive rate (Ro) was
      101.04 and the intrinsic rate of increase (rm) was 0.15 with a mean generation
      time (G) of 30.7 d. The instantaneous mean of birth (B) and death rate (D) were
      0.30 and 0.15, respectively, with rm/B of 0.529 and B/D of 2.281. Compared to
      other Ae. aegypti strains from different geographic and ecological settings, the
      Saudi strain had a relatively low colonization potential. This is the first
      report on life table characteristics for Ae. aegypti from the Arabian Peninsula,
      and provides base-line information for wider studies on its natural populations.
      This is particularly important for understanding its population dynamics in
      relation to dengue transmission and control under regional conditions. 

PMID- 23959497
TI  - Pediculicidal effect of herbal shampoo against Pediculus humanus capitis in
      vitro.
AB  - Human head lice infestation is an important public health problem in Thailand.
      Lice resistance is increasing, chemical pediculicides have lost their efficacy
      and thus alternative products such as herbal shampoos have been proposed to treat
      lice infestation. The present study investigated the efficacy of twenty nine
      herbal shampoos based on zinbiberaceae plants, piperaceae plants and native
      plants against human head lice and compared them with malathion shampoo (A-lices
      shampoo(r): 1% w/v malathion) and commercial shampoo (BabiMild Natural'N Mild(r))
      in order to assess their in vitro efficacy. All herbal shampoo were more
      effective than commercial shampoo with 100% mortality at 60 seconds and LT50
      values ranged from 11.30 to 31.97 seconds, meanwhile, commercial shampoo caused
      14.0-15.0% mortality and LT50 values ranged from 83.96 to 87.43 seconds. The nine
      herbal shampoos from Zingiber cassumunar, Piper betle, Piper ribesioides,
      Averrhoa bilimbi, Clitoria ternatea, Plectranthus amboincus, Myristica fragrans,
      Tacca chantrieri and Zanthoxylum limonella were more effective pediculicide than
      malathion shampoo with 100% mortality at 30 seconds and LT50 values ranged from
      11.30-13.58 seconds, on the other hand malathion shampoo showed LT50 values
      ranging from 12.39 to 13.67 seconds. LT50 values indicated the order of
      pediculicidal activity in the herbal shampoos as Z. cassumunar shampoo > P. betle
      shampoo > Za. limonella shampoo > Av. bilimbi shampoo > P. ribesioides shampoo >
      My. fragrans shampoo > T. chantrieri shampoo > Pl. amboincus shampoo. Our data
      showed that eight of the twenty nine herbal shampoos in this study were of high
      potential pediculicide to human head lice treatments for Thai children. 

PMID- 23959498
TI  - Morphology and identification of fly eggs: application in forensic entomology.
AB  - Fly eggs found in corpses can be used as entomological evidence in forensic
      investigation. This study aims to investigate the morphology of forensically
      important fly eggs. Eggs of Chrysomya rufifacies, Chrysomya megacephala,
      Chrysomya pinguis, Chrysomya nigripes, Hypopygiopsis tumrasvini, Lucilia cuprina,
      Lucilia porphyrina and Musca domestica were examined using 1% potassium
      permanganate solution for 1 min. Morphometric analysis revealed that the mean
      length of Hy. tumrasvini (1.63 mm) and C. pinguis (1.65 mm) eggs was the longest,
      followed by that of L. porphyrina (1.45 mm), C. rufifacies (1.34 mm). The egg
      length, width of median area and darkness staining of hatching pleats were
      distinctive features. Four categories of median area were proposed, based on
      width; (1) distinctly wide (Megaselia scalaris, Synthesiomyia nudiseta); (2) wide
      (C. nigripes, M. domestica); (3) slightly widening (Hy. tumrasvini, L. cuprina,
      L. porphyrina); and (4) narrow (C. rufifacies, C. albiceps, C. megacephala, C.
      pinguis). Four species were examined using SEM, i.e., C. megacephala, C. pinguis,
      Hy. tumrasvini and L. porphyrina. The eggs of C. megacephala demonstrated swollen
      hatching pleats. Inside, the hexagon of the chorion appeared as a sponging bumpy
      feature. The egg of C. pinguis was similar to C. megacephala, except for the
      sponging bumpy feature on the outer surface of the hatching pleats. Regarding Hy.
      tumrasvini and L. porphyrina, their island structure was apparent at the inner
      surface of the upright hatching pleats. The key for identifying these eggs
      together with other reported species in Thailand has been updated. 

PMID- 23959499
TI  - Evaluation of PCR-based approach for serotype determination of Streptococcus
      pneumoniae.
AB  - Determination of Streptococcus pneumoniae serotypes is essential for
      epidemiological surveillance. Therefore accurate, reliable and cost effective
      serotyping method is crucial. In this study, we determined the serotypes of 41
      pneumococcal isolates recovered from human anterior nares by multiplex Polymerase
      Chain Reaction (PCR) utilizing published primers. The data was then compared with
      conventional serology using latex agglutination (LA) and the Quellung reaction.
      Based on the PCR-approach, 8 different serogroups/serotypes were detected with
      one isolate classified as non-typeable (cpsA-negative). In reference to the
      serology-based data, the results were in agreement except for one isolate. For
      the latter isolate, the LA and Quellung tests failed to show a reaction but the
      PCR-approach and sequencing identified the isolate as serogroup 15B/C. Based on
      this experimental setting, we found that the PCR-approach for pneumococcal
      serotypes determination is reliable to serve as the alternative for determining
      the pneumococcal serotyping. 

PMID- 23959500
TI  - Molecular detection of Anaplasma platys and Babesia gibsoni in dogs in Malaysia.
AB  - This study reports for the first time molecular detection of Anaplasma platys
      infection in 4 (13.3%) of 30 Malaysian dogs investigated. A low occurrence (3.3%)
      of Babesia gibsoni was also noted, being detected in one of the 30 dogs.
      Rickettsia, Bartonella, Orientia tsutsugamushi, and Ehrlichia DNA were not
      detected in the dog blood samples. The role of A. platys as an agent of canine
      anaplasmosis and its transmission through Rhipicephalus sanguineus ticks merits
      further investigation. 

PMID- 23959501
TI  - Suspension culture of Neospora caninum by Theileria annulata-infected cell line.
AB  - There are some limiting aspects of scaling up the Neospora caninum tachyzoites in
      continuous cell lines, particularly as related to the absence of surface
      attachment. In this study, suspension cell culture of Theileria annulata-infected
      lymphoblastoid (TIL) was used as a host cell for the continous production of N.
      caninum tachyzoites. The numbers of free tachyzoites in the medium supernatant
      were showed regularly increased up to the day 6 post-cultivation. Transmission
      electron microscopy demonstrated that N. caninum tachyzoites invaded the TIL
      cells and multiplied intracellularly. This showed that the tachyzoites were
      successfully proliferated in TIL cells and were released in complete Dulbecco's
      modified Eagle's medium. This is a successful report of in vitro cultivation of
      N. caninum tachyzoites achieved by using suspension host cell culture. 

PMID- 23959502
TI  - Adderall for All: A Defense of Pediatric Neuroenhancement.
AB  - I argue that young patients should be able to access neuroenhancing drugs without
      a diagnosis of ADHD. The current framework of consent for pediatric patients can
      be adapted to accommodate neuroenhancement. After a brief overview of pediatric
      neuroenhancement, I develop three arguments in favor of greater acceptance of
      neuroenhancement for young patients. First, ADHD is not relevantly different from
      other disadvantages that could be treated with stimulant medication. Second,
      establishing a legitimate framework for pediatric neuroenhancement would mitigate
      the bad effects of diversion and improve research on neuroenhancement and ADHD.
      Third, some pediatric patients have rights to access neuroenhancements. I then
      consider several objections to pediatric neuroenhancement. I address concerns
      about addiction, advertising, authentic development, the parent-child
      relationship and equal opportunity and conclude that these concerns may inform a
      framework for prescribing neuroenhancement but they do not justify limits on
      prescribing.

PMID- 23959503
TI  - Dysbiosis contributes to fibrogenesis in the course of chronic liver injury in
      mice.
AB  - Nonalcoholic fatty liver disease (NAFLD) may lead to hepatic fibrosis. Dietary
      habits affect gut microbiota composition, whereas endotoxins produced by Gram
      negative bacteria stimulate hepatic fibrogenesis. However, the mechanisms of
      action and the potential effect of microbiota in the liver are still unknown.
      Thus, we sought to analyze whether microbiota may interfere with liver
      fibrogenesis. Mice fed control (CTRL) or high-fat diet (HFD) were subjected to
      either bile duct ligation (BDL) or CCl4 treatment. Previously gut-sterilized mice
      were subjected to microbiota transplantation by oral gavage of cecum content
      obtained from donor CTRL- or HFD-treated mice. Fibrosis, intestinal permeability,
      bacterial translocation, and serum endotoxemia were measured. Inflammasome
      components were evaluated in gut and liver. Microbiota composition (dysbiosis)
      was evaluated by Pyrosequencing. Fibrosis degree was increased in HFD+BDL versus
      CTRL+BDL mice, whereas no differences were observed between CTRL+CCl4 and
      HFD+CCl4 mice. Culture of mesenteric lymph nodes showed higher density of
      infection in HFD+BDL mice versus CTRL+BDL mice, suggesting higher bacterial
      translocation rate. Pyrosequencing revealed an increase in percentage of Gram
      negative versus Gram-postive bacteria, a reduced ratio between Bacteroidetes and
      Firmicutes, as well as a dramatic increase of Gram-negative Proteobacteria in
      HFD+BDL versus CTRL+BDL mice. Inflammasome expression was increased in liver of
      fibrotic mice, but significantly reduced in gut. Furthermore, microbiota
      transplantation revealed more liver damage in chimeric mice fed CTRL diet, but
      receiving the microbiota of HFD-treated mice; liver damage was further enhanced
      by transplantation of selected Gram-negative bacteria obtained from cecum content
      of HFD+BDL-treated mice. CONCLUSIONS: Dietary habits, by increasing the
      percentage of intestinal Gram-negative endotoxin producers, may accelerate liver
      fibrogenesis, introducing dysbiosis as a cofactor contributing to chronic liver
      injury in NAFLD.

PMID- 23959504
TI  - Development of an expedient intramolecular Pauson-Khand reaction approach to
      stereoselectively construct the trans-decalin with a C1 quaternary chiral center.
AB  - Stereoselective synthesis of the trans-decalin subunit with a defined C1
      quaternary chiral center has been achieved by the Pauson-Khand reaction (PKR) as
      a key step. The developed chemistry offers an alternative to the IMDA reaction
      that has been used for the syntheses of trans-decalin based biologically active
      natural products. 

PMID- 23959505
TI  - Rapid development of tissue bank achieved by International  Atomic Energy Agency
      (IAEA) Tissue Banking Programme  in China.
AB  - Before 1986, the development of tissue banking in China has been slow and
      relatively uncoordinated. Under the support of International Atomic Energy Agency
      (IAEA), Tissue Banking in China experienced rapid development. In this period,
      China Institute for Radiation Protection tissue bank mastered systematic and
      modern tissue banking technique by IAEA training course and gradually developed
      the first regional tissue bank (Shanxi Provincial Tissue Bank, SPTB) to provide
      tissue allograft. Benefit from training course, SPTB promoted the development of
      tissue transplantation by ways of training, brochure, advertisement and meeting.
      Tissue allograft transplantation acquired recognition from clinic and supervision
      and administration from government. Quality system gradually is developing and
      perfecting. Tissue allograft transplantation and tissue bank are developing
      rapidly and healthy.

PMID- 23959506
TI  - MULTIVARIATE MODELING OF LONGITUDINAL MRI IN EARLY BRAIN DEVELOPMENT WITH
      CONFIDENCE MEASURES.
AB  - The human brain undergoes rapid organization and structuring early in life.
      Longitudinal imaging enables the study of these changes over a developmental
      period within individuals through estimation of population growth trajectory and
      its variability. In this paper, we focus on maturation of white and gray matter
      depicted in structural and diffusion MRI of healthy subjects with repeated scans.
      We provide a framework for joint analysis of both structural MRI and DTI
      (Diffusion Tensor Imaging) using multivariate nonlinear mixed effect modeling of
      temporal changes. Our framework constructs normative growth models for all the
      modalities, taking into account the correlation among the modalities and
      individuals, along with estimation of the variability of the population trends.
      We apply our method to study early brain development, and to our knowledge this
      is the first multimodel longitudinal modeling of diffusion and signal intensity
      changes for this growth stage. Results show the potential of our framework to
      study growth trajectories, as well as neurodevelopmental disorders through
      comparison against the constructed normative models of multimodal 4D MRI.

PMID- 23959507
TI  - [Highlights from previous issues of Klinische Monatsblatter fur Augenheilkunde ].

PMID- 23959508
TI  - [Highlights from today's issue of Klinische Monatsblatter fur Augenheilkunde].

PMID- 23959509
TI  - [Multifocal IOL optics and aniridia therapy].

PMID- 23959510
TI  - [Long-term visual outcome comparison of bilateral implantation of apodised
      diffractive versus progressive multizonal refractive multifocal intraocular
      lenses after cataract extraction].
AB  - AIM: The aim of this study was to evaluate the functional effect of bilateral
      implantation of apodised diffractive versus progressive multizonal refractive
      multifocal intraocular lenses compared to standard monofocal intraocular lenses.
      PATIENTS AND METHOD: 229 patients underwent cataract extraction; 66 Array SA40N
      (AMO, Irvine, CA, USA), 76 SA60D3 ReSTOR (Alcon, Fort Worth, TX, USA), and 87
      MA60AC (Alcon, Fort Worth, TX, USA) were implanted. In this retrospective trial
      the main outcome measures were near, intermediate, and distance visual acuity and
      assessment of subjective function by questionnaire. RESULTS: Mean follow-up was
      4.7 +/- 1.4 years with monofocal, 6.6 +/- 1.7 with Array and 4.3 +/- 1.1 with
      ReSTOR implants. Uncorrected binocular distance visual acuity was equivalent in
      the three groups. Uncorrected binocular near and intermediate visual acuity and
      spectacle independence were significantly higher in the two multifocal groups (p
      < 0.001). Glare and halos were more bothersome with multifocal than monofocals
      implants (p < 0.05) and adverse visual symptoms at night with Array implants but
      equivalent between ReSTOR patients and monofocal patients. Between the two
      multifocal groups spectacle independence was higher and adverse visual symptoms
      lower in ReSTOR patients than in Array patients (p < 0.05). ReSTOR patients
      reported a higher overall visual satisfaction than the other groups (p < 0.001)
      and rated their vision at 8.8 +/- 1.8. Monofocal patients reported a slightly
      higher satisfaction at 7.6 +/- 1.7 compared to Array patients at 6.9 +/- 2.6 (p =
      0.05). CONCLUSION: In this long-term study the highest overall visual
      satisfaction could be achieved by bilateral implantation of apodised diffractive
      intraocular lenses.

PMID- 23959511
TI  - [Ocular cicatricial pemphigoid - state of the art in clinic and therapy for a
      problematic disease].
AB  - The ocular cicatricial pemphigoid (OCP) belongs to a family of chronically
      progressive autoimmune disorders, predominantly affecting mucous membranes
      (mucous membrane pemphigoids). It is an immunopathologically heterogeneous group
      of disorders with variable phenotypes that share the unique feature of a
      subepidermal blistering, through disruption of the adhesion between epidermis and
      dermis. A key feature is the chronically active inflammation with consecutive
      fibrosis, leading to a partial or complete loss of function of the affected
      organ. The ocular disease as a chronic cicatrising conjunctivitis is a common
      manifestation of the mucous membrane pemphigoid. The identification of the subtle
      pathology and the prompt initiation of an appropriate therapy are of pivotal
      importance. One purpose is to prevent further vision loss due to extensive
      corneal scarring and life-threatening systemic complications, such as the
      formation of oesophageal or tracheal strictures. So far there are no prospective,
      randomised studies, regarding the therapy guidelines with an evidence level more
      than III. The autoimmune nature of the disease implies that systemic
      immunosuppression is the only effective treatment option, most notably in
      extended stages. The aim of our study is to give a guideline for a stage adjusted
      therapy with conventional immunosuppressants and to give a perspective for
      alternative therapies, especially for recalcitrant disease.

PMID- 23959512
TI  - [Characteristics of traumatic versus spontaneous wound dehiscence after
      penetrating keratoplasty].
AB  - BACKGROUND AND PURPOSE: After penetrating keratoplasty (PK) patients remain at
      risk for wound dehiscence at the graft-host junction even years after surgery.
      The aim of our study was, firstly, to assess the site-specific characteristics
      between traumatic and spontaneous wound dehiscence at the graft-host junction
      and, secondly, to determine the incidence of traumatic and spontaneous wound
      dehiscence. METHODS: The medical records of all 243 patients who underwent a
      penetrating keratoplasty from 1 March 1996 to 1 March 2012 were retrospectively
      reviewed. During a 16-year period 9 eyes showed signs of open wound dehiscence
      after blunt ocular trauma and 7 eyes spontaneously after suture removal. RESULTS:
      Over the 16-year period, the incidence of traumatic wound dehiscence was 3.7 % (9
      of patients), whereas the incidence of spontaneous wound dehiscence after suture
      removal was 2.9 % (7 of 243 patients). In traumatic cases the graft dehiscence
      occurred in 88.9 % (8 of 9 patients) in the nasal part, predominantly in the
      inferior nasal part. In one case (11.1 %), only the temporal part was affected.
      The average extent of wound dehiscence for traumatic cases was 96 degrees  of the
      total wound circumference in the nasal part, and only 30 degrees  of the
      circumference in the temporal part. Spontaneous dehiscence after suture removal
      mainly occurred at temporal site in 71.4 % (5 of 7 eyes), mostly temporal
      inferior. Only in one case was the nasal part affected (14.3 %). The average
      extent of wound dehiscence in spontaneous cases was 54 degrees  of the total
      circumference in the temporal part and 21 degrees  in the nasal part. The total
      average extent of dehiscence was significantly larger in traumatic cases, 126
      degrees  (one third) for traumatic and 75 degrees  (one fifth) of the wound
      circumference for spontaneous cases. All of the re-sutured grafts retained
      clarity, except for 3 eyes among the traumatic cases. CONCLUSION: The difference
      between both groups was significant regarding the localisation, the extent and
      the clarity of the re-sutured grafts. The nasal inferior part was the most
      affected area in traumatic cases probably as a result of indirect, contrecoup
      injuries, and the temporal part in spontaneous wound dehiscence probably due to
      direct minor forces.

PMID- 23959513
TI  - [Visual impairment and blindness in children in a Malawian school for the blind].
AB  - PURPOSE: The aim of this study was to determine the anatomic sites of severe
      visual impairment and blindness in children in an integrated school for the blind
      in Malawi, and to compare the results with those of previous Malawian blind
      school studies. METHODS: Children attending an integrated school for the blind in
      Malawi were examined in September 2011 using the standard WHO/PBL eye examination
      record for children with blindness and low vision. Visual acuity [VA] of the
      better eye was classified using the standardised WHO reporting form. RESULTS:
      Fifty-five pupils aged 6 to 19 years were examined, 39 (71 %) males, and 16 (29
      %) females. Thirty eight (69%) were blind [BL], 8 (15 %) were severely visually
      impaired [SVI], 8 (15 %) visually impaired [VI], and 1 (1.8 %) was not visually
      impaired [NVI]. The major anatomic sites of visual loss were optic nerve (16 %)
      and retina (16 %), followed by lens/cataract (15 %), cornea (11 %) and lesions of
      the whole globe (11 %), uveal pathologies (6 %) and cortical blindness (2 %). The
      exact aetiology of VI or BL could not be determined in most children. Albinism
      accounted for 13 % (7/55) of the visual impairments. 24 % of the cases were
      considered to be potentially avoidable: refractive amblyopia among pseudophakic
      patients and corneal scaring. CONCLUSIONS: Optic atrophy, retinal diseases
      (mostly albinism) and cataracts were the major causes of severe visual impairment
      and blindness in children in an integrated school for the blind in Malawi.
      Corneal scarring was now the fourth cause of visual impairment, compared to being
      the commonest cause 35 years ago. Congenital cataract and its postoperative
      outcome were the commonest remedial causes of visual impairment.

PMID- 23959514
TI  - [Conjunctival infections].

PMID- 23959515
TI  - Completing the play or dropping the ball?: The case for comprehensive patient
      centered discharge planning.

PMID- 23959516
TI  - N-heterocyclic carbene-catalyzed highly enantioselective synthesis of substituted
      dihydropyranopyrazolones.
AB  - Highly optically pure multisubstituted dihydropyrano[2,3-c]pyrazol-6-(1H)-ones
      were synthesized via the N-heterocyclic carbene-catalyzed enantioselective [4 +
      2] annulation of alpha-chloroaldehydes and pyrazolone-derived oxodienes. 

PMID- 23959517
TI  - Gold nanoparticles protected by fluorinated ligands for 19F MRI.
AB  - Gold nanoparticles coated with fluorinated ligands (F-MPCs) present features
      suitable for (19)F MRI as observed from phantom experiments. Cellular uptake, by
      HeLa cells, and toxicity of fluorescent dye-decorated F-MPCs are presented
      together with their ability to bind hydrophobic molecules allowing for a
      potential combination of targeting, delivery and imaging features. 

PMID- 23959518
TI  - Electronic nose can discriminate colorectal carcinoma and advanced adenomas by
      fecal volatile biomarker analysis: proof of principle study.
AB  - In the course and prognosis of colorectal cancer (CRC), early detection and
      treatment are essential factors. Fecal immunochemical tests (FITs) are currently
      the most commonly used non-invasive screening tests for CRC and premalignant
      (advanced) adenomas, however, with restricted sensitivity. We hypothesized that
      fecal volatile organic compounds (VOCs) may serve as a diagnostic biomarker of
      CRC and adenomas. In this proof of concept study, we aimed to assess disease
      specific VOC smellprints in fecal gas to distinguish patients with CRC and
      advanced adenomas from healthy controls. Fecal samples of patients who were
      scheduled to undergo an elective colonoscopy were collected. An electronic nose
      (Cyranose 320) was used to measure VOC patterns in fecal gas from patients with
      histopathologically proven CRC, with advanced adenomas and from controls (no
      abnormalities seen at colonoscopy). Receiver operator characteristic curves and
      corresponding sensitivity and specificity for detection of CRC and advanced
      adenomas were calculated. A total of 157 stool samples (40 patients with CRC, 60
      patients with advanced adenomas, and 57 healthy controls) were analyzed by
      electronic nose. Fecal VOC profiles of patients with CRC differed significantly
      from controls (area under curve +/- 95%CI, p-value, sensitivity, specificity;
      0.92 +/- 0.03, <0.001, 85%, 87%). Also VOC profiles of patients with advanced
      adenomas could be discriminated from controls (0.79 +/- 0.04, <0.001, 62%, 86%).
      The results of this proof of concept study suggest that fecal gas analysis by an
      electronic nose seems to hold promise as a novel screening tool for the (early)
      detection of advanced neoplasia and CRC.

PMID- 23959519
TI  - Randomized clinical trial to evaluate the efficacy and safety of valganciclovir
      in a subset of patients with chronic fatigue syndrome.
AB  - There is no known treatment for chronic fatigue syndrome (CFS). Little is known
      about its pathogenesis. Human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV)
      have been proposed as infectious triggers. Thirty CFS patients with elevated IgG
      antibody titers against HHV-6 and EBV were randomized 2:1 to receive
      valganciclovir (VGCV) or placebo for 6 months in a double-blind, placebo
      controlled trial. Clinical endpoints aimed at measuring physical and mental
      fatigue included the Multidimensional Fatigue Inventory (MFI-20) and Fatigue
      Severity Scale (FSS) scores, self-reported cognitive function, and physician
      determined responder status. Biological endpoints included monocyte and
      neutrophil counts and cytokine levels. VGCV patients experienced a greater
      improvement by MFI-20 at 9 months from baseline compared to placebo patients but
      this difference was not statistically significant. However, statistically
      significant differences in trajectories between groups were observed in MFI-20
      mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive
      function (P = 0.025). VGCV patients experienced these improvements within the
      first 3 months and maintained that benefit over the remaining 9 months. Patients
      in the VGCV arm were 7.4 times more likely to be classified as responders (P =
      0.029). In the VGCV arm, monocyte counts decreased (P < 0.001), neutrophil counts
      increased (P = 0.037) and cytokines were more likely to evolve towards a Th1
      profile (P < 0.001). Viral IgG antibody titers did not differ between arms. VGCV
      may have clinical benefit in a subset of CFS patients independent of placebo
      effect, possibly mediated by immunomodulation and/or antiviral effect. Further
      investigation with longer treatment duration and a larger sample size is
      warranted.

PMID- 23959520
TI  - Association between endothelial dysfunction and frailty: the Toledo Study for
      Healthy Aging.
AB  - Cardiovascular disease (CVD), both clinical and subclinical, has been proposed as
      one of the mechanisms underlying frailty. However, there is no evidence
      addressing the relationship between the earliest stage of CVD (endothelial
      dysfunction) and frailty. The goal of the study was to analyze the association
      between endothelial dysfunction, evaluated by asymmetric dimethylarginine (ADMA)
      levels, and frailty. We used data from the Toledo Study for Healthy Aging, a
      prospective Spanish cohort study. Biological samples were obtained and ADMA
      levels were determined using an enzyme immunoassay method. Logistic regression
      was used to estimate the odds ratio (OR) and 95 % confidence intervals of frailty
      associated with ADMA. Adjustments were made for age, gender, cardiovascular risk
      factors, and presence of atherosclerotic disease (assessed by ankle-brachial
      index; ABI). One thousand two hundred eighty-seven community-dwelling elderly
      were included. One hundred seven (8.3 %) were identified as frail, 542 (42.1 %)
      as pre-frail, and 638 (49.6 %) as non-frail. ADMAvalues were higher in frail
      subjects than in non-frail ones. In addition, an interaction between the presence
      of atherosclerotic disease and ADMA on the odds of frailty (p=0.045) was
      detected. After adjustments for age, classical cardiovascular risk factors, and
      ABI, the risk of frailty was associated with increasing levels of ADMA in
      subjects without atherosclerotic disease [OR for 1 standard deviation increase in
      ADMA=1.14 (1.01-1.28), p=0.032] but not in those with atherosclerotic disease. In
      our study, endothelial dysfunction, assessed by ADMA levels, is associated with
      frailty. These findings provide additional support for a relevant role of
      vascular system since its earliest stage in frailty.

PMID- 23959521
TI  - Alternative management of anastomotic colorectal strictures: our experience with
      fully covered self-expanding metal stents.

PMID- 23959522
TI  - Sedation for interventional gastrointestinal endoscopic procedures: are we
      overlooking the "pain"?
AB  - BACKGROUND: Although interventional gastrointestinal (GI) endoscopic procedures
      are known to cause greater pain and discomfort than diagnostic procedures, the
      efficacy of adequate pain control or the difference in pain and amount of
      analgesic required according to type of intervention is not well known. This
      study was done to investigate the safety and efficacy of combining fentanyl with
      propofol for interventional GI endoscopic procedures and determine whether this
      method is superior to propofol monosedation. METHODS: The data of 810 patients
      that underwent interventional GI endoscopic procedures under sedation with either
      propofol alone (Group P, n = 499) or propofol/fentanyl (Group PF, n = 311) at a
      single tertiary-care hospital between May 2012 and December 2012 were
      retrospectively reviewed. Rates of respiratory and cardiovascular events,
      propofol and fentanyl requirements, and risk factors of respiratory events of the
      two groups were analyzed. RESULTS: The incidence of respiratory events (P =
      0.001), number of cases in which the procedure had to be interrupted for assisted
      mask bagging (P = 0.044), and propofol infusion rates were significantly lower in
      Group PF compared to Group P (P < 0.0001). The amount of fentanyl required for
      diagnostic procedures was significantly lower than that for interventional
      procedures (P < 0.001). Patients of Group PF showed a lower risk of developing
      respiratory events compared to Group P (OR 0.224, 95 % CI 0.069-0.724).
      CONCLUSIONS: Combining fentanyl with propofol seems to reduce the risk of
      respiratory events compared with propofol monosedation during GI endoscopic
      procedures by providing effective analgesia.

PMID- 23959523
TI  - Colonic architectural changes following use of psychotropic drugs: looking at the
      egg while forgetting the hen?

PMID- 23959524
TI  - Force-induced mechanical response of molecule-metal interfaces: molecular
      nanomechanics of propanethiolate self-assembled monolayers on Au(111).
AB  - Density-functional theory calculations of propanethiolate self-assembled
      monolayers at the Au(111) surface have been carried out to study the response
      properties of organic adlayers at metal surfaces to externally applied mechanical
      forces. "Force maps" are introduced in order to systematically quantify the
      system's nanomechanical response to both the magnitude and direction of the
      external forces applied here in an isotensional setup. Depending on the direction
      and magnitude of the forces we find that there are two dominant phenomena for the
      most stable c(4 * 2) structure containing two propanethiolate gold adatom
      adsorbate complexes C3S-Auad-SC3 per unit cell: a sliding of the complete topmost
      metal layer including adsorbates or the detachment of the thiolate-adatom
      complexes only. Investigations of the atomistic mechanisms show that the initial
      configuration of the bulky C3S-Auad-SC3 complexes is responsible for sizable
      variations in the effective barrier heights for different force directions. A
      lateral force along the [11[combining macron]0] direction with magnitude between
      0.6 nN and 1.4 nN induces a plane sliding of the complete outermost Au(111)
      layer. In contrast, a force normal to the surface induces a detachment of the
      thiolate complexes if the force exceeds a threshold value of about 1.4 nN, which
      is in excellent agreement with experimental results. The use of tilted pulling
      directions, i.e., applying forces with nonzero normal and lateral components,
      facilitates the removal of the adsorbate complexes even at notably smaller force
      magnitudes. This mechanochemical promotion is traced back to a destabilization of
      the molecule-metal interface as a result of a (slight) lateral displacement to
      energetically unfavorable sites, thereby weakening chemical bonding of adsorbate
      complexes to the substrate. These observations are vastly different from what has
      been found for single molecule pulling normal to the surface, where nanowire
      formation is typically observed. Overall, a rich spectrum of nanomechanical
      response scenarios is revealed by these explorative calculations, which is
      expected to significantly grow upon varying further parameters such as the chain
      length, surface plane, and substrate metal. 

PMID- 23959525
TI  - Linkage mapping and identification of QTL affecting deoxynivalenol (DON) content
      (Fusarium resistance) in oats (Avena sativa L.).
AB  - Mycotoxins caused by Fusarium spp. is a major concern on food and feed safety in
      oats, although Fusarium head blight (FHB) is often less apparent than in other
      small grain cereals. Breeding resistant cultivars is an economic and environment
      friendly way to reduce toxin content, either by the identification of resistance
      QTL or phenotypic evaluation. Both are little explored in oats. A recombinant
      inbred line population, Hurdal * Z595-7 (HZ595, with 184 lines), was used for QTL
      mapping and was phenotyped for 3 years. Spawn inoculation was applied and
      deoxynivalenol (DON) content, FHB severity, days to heading and maturity (DH and
      DM), and plant height (PH) were measured. The population was genotyped with
      DArTs, AFLPs, SSRs and selected SNPs, and a linkage map of 1,132 cM was
      constructed, covering all 21 oat chromosomes. A QTL for DON on chromosome 17A/7C,
      tentatively designated as Qdon.umb-17A/7C, was detected in all experiments using
      composite interval mapping, with phenotypic effects of 12.2-26.6 %. In addition,
      QTL for DON were also found on chromosomes 5C, 9D, 13A, 14D and unknown_3, while
      a QTL for FHB was found on 11A. Several of the DON/FHB QTL coincided with those
      for DH, DM and/or PH. A half-sib population of HZ595, Hurdal * Z615-4 (HZ615,
      with 91 lines), was phenotyped in 2011 for validation of QTL found in HZ595, and
      Qdon.umb-17A/7C was again localized with a phenotypic effect of 12.4 %. Three
      SNPs closely linked to Qdon.umb-17A/7C were identified in both populations, and
      one each for QTL on 5C, 11A and 13A were identified in HZ595. These SNPs,
      together with those yet to be identified, could be useful in marker-assisted
      selection to pyramiding resistance QTL.

PMID- 23959526
TI  - An intra-specific linkage map of lettuce (Lactuca sativa) and genetic analysis of
      postharvest discolouration traits.
AB  - Minimally processed salad packs often suffer from discolouration on cut leaf
      edges within a few days after harvest. This limits shelf life of the product and
      results in high wastage. Recombinant inbred lines (RILs) derived from a cross
      between lettuce cvs. Saladin and Iceberg were shown to be suitable for genetic
      analysis of postharvest discolouration traits in lettuce. An intra-specific
      linkage map based on this population was generated to enable genetic analysis. A
      total of 424 markers were assigned to 18 linkage groups covering all nine
      chromosomes. The linkage map has a total length of 1,040 cM with an average
      marker distance of 2.4 cM within the linkage groups and was anchored to the ultra
      dense, transcript-based consensus map. Significant genetic variation in the
      postharvest traits 'pinking', 'browning' and 'overall discolouration' was
      detected among the RILs. Seven significant quantitative trait loci (QTL) were
      identified for postharvest discolouration traits providing markers linked to the
      QTL that can be used for marker-assisted selection. Phenotypic stability was
      confirmed for extreme lines possessing the corresponding QTL parental alleles and
      which had shown transgressive segregation. This study indicates that a desired
      phenotype with reduced levels of postharvest discolouration can be achieved by
      breeding using natural variation.

PMID- 23959527
TI  - Smad7 modulates TGFbeta signaling during cranial suture development to maintain
      suture patency.
AB  - Craniosynostosis, the premature fusion of one or more sutures between the
      calvarial bones, is a common birth defect. Mutations in genes encoding receptors
      for the transforming growth factor-beta (TGFbeta) family of signaling molecules
      have been associated with craniosynostosis, but how TGFbeta signaling is
      regulated during suture development is not known. In the present study, we found
      that expression of Smad2 and Smad3, intracellular mediators of canonical TGFbeta
      signaling, gradually increases during early postnatal suture development in rat
      in both the coronal suture (CS), which remains patent throughout life, and the
      posterior frontal suture (PFS), which undergoes programmed closure by postnatal
      day 22. The amounts of phosphorylated Smad2 and Smad3 proteins showed a similar
      gradual increase in the PFS and CS, but in the CS, Smad2/3 activation was
      suppressed after neonatal day 10. The suppression of Smad2/3 activation in the CS
      correlated with upregulation of Smad7 expression. We demonstrate that siRNA
      mediated knockdown of Smad7 caused increased phosphorylation of Smad2 and Smad3
      and induced osseous obliteration of the CS from postnatal days 10 to 22. The
      Smad7 siRNA-induced CS closure was associated with significantly increased levels
      of Fgf10 and phosphorylated ERK1/2 in the suture mesenchyme. Moreover, addition
      of the Erk1/2 inhibitor U0126 partially blocked Smad7-siRNA-induced CS closure.
      These findings suggest that canonical TGFbeta signaling induces suture closure at
      least in part through activation of FGF and ERK signaling and that Smad7 plays an
      important role in maintaining suture patency by suppressing canonical TGFbeta
      signaling during suture development.

PMID- 23959529
TI  - Gadolinium(III)-hydroxy ladders trapped in succinate frameworks with optimized
      magnetocaloric effect.
AB  - Two kinds of inorganic gadolinium(III)-hydroxy "ladders", [2*n] and [3*n], were
      successfully trapped in succinate (suc) coordination polymers,
      [Gd2(OH)2(suc)2(H2O)]n.2nH2O (1) and [Gd6(OH)8(suc)5(H2O)2 ]n.4n H2O (2),
      respectively. Such coordination polymers could be regarded as alternating
      inorganic-organic hybrid materials with relatively high density. Magnetic and
      heat capacity studies reveal a large cryogenic magnetocaloric effect (MCE) in
      both compounds, namely (DeltaH=70 kG) 42.8 J kg(-1) K(-1) for complex 1 and 48.0
      J kg(-1) K(-1) for complex 2. The effect of the high density is evident, which
      gives very large volumetric MCEs up to 120 and 144 mJ cm(-3) K(-1) for complexes
      1 and 2, respectively.

PMID- 23959528
TI  - Proteins involved in building, maintaining and remodeling of yeast cell walls.
AB  - The cell wall defines the shape and provides osmotic stability to the yeast cell.
      It also serves to anchor proteins required for communication of the yeast cell
      with surrounding molecules and other cells. It is synthesized as a complex
      structure with beta-1,3-glucan chains forming the basic network to which beta-1,6
      glucan, chitin and a number of mannoproteins are attached. Synthesis, maintaining
      and remodeling of this complex structure require a set of different synthases,
      hydrolases and transglycosidases whose concerted activities provide necessary
      firmness but at the same time flexibility of the wall moiety. The present state
      of comprehension of the interplay of these proteins in the yeast cell wall is the
      subject of this article.

PMID- 23959530
TI  - Prevalence of intracranial large artery stenosis and occlusion in patients with
      acute ischaemic stroke or TIA.
AB  - Intracranial large artery stenosis and occlusion disease has been considered to
      be the cause of 8-10 % of ischaemic strokes in North America, and 30-50 % of
      strokes and more than 50 % of transient ischaemic attacks in Chinese population.
      So far we do not know the real prevalence of intracranial disease (ID) and the
      distribution of its risk factors in European population. We aimed to determine
      the prevalence and risk factors of ID in a European stroke population with
      computed tomography angiography (CTA). A retrospective study of consecutive
      ischaemic patients at the Stroke Unit of Utrecht, The Netherlands, from September
      2006 to August 2008 was conducted. We assessed the presence of occlusion and/or
      stenosis of intracranial Internal Carotid Artery (ICA) and Middle Cerebral Artery
      on post-contrast 30-mm reconstruction axial CTA images. We analyzed the
      proportion of patients with ID, and the association of ID with risk factors and
      stroke subtype. In 220 patients (187 with stroke, 33 with TIA; mean age was 65
      years, 57.3 % were male), intracranial stenosis was found in 6.4 % (95 % CI 3.9
      10.4), intracranial occlusion in 34.5 % (95 % CI 28.6-41.0), and both occlusion
      and stenosis in 2.3 % (95 % CI 1.0-5.2). Multivariate analysis showed that the
      variables independently associated with ID were: extracranial ICA atherosclerosis
      (OR, 24.64; 95 % CI 6.30-96.38) and stroke subtypes TACS-PACS (OR, 7.61; 95 % CI
      3.31-17.49). In conclusion, prevalence of intracranial stenosis in our study may
      well be consistent with previous observations in European and non-European
      population. ID may have been an underestimated condition in ischaemic Caucasian
      population.

PMID- 23959531
TI  - Misdiagnosis of herpes zoster neuralgia: nerve ultrasound allowed diagnosing
      schwannoma of the intercostal nerve.

PMID- 23959532
TI  - Awareness of cognitive deficits and clinical competence in mild to moderate
      Alzheimer's disease: their relevance in clinical practice.
AB  - Awareness of cognitive deficits and clinical competence were investigated in 79
      mild to moderate Alzheimer's disease patients. Awareness was assessed by the
      anosognosia questionnaire for dementia, and clinical competence by specific
      neuropsychological tests such as trail making test-A, Babcock story recall test,
      semantic and phonemic verbal fluency. The findings show that 66 % of the patients
      were aware of memory deficits, while the 34 % were unaware. Deficit in awareness
      correlated with lower scores on the Mini Mental State Examination test that, in
      the score range from 24.51 to 30 and from 19.50 to 24.50, appeared to be a
      significant predictor of level of awareness. None of the AD patients had fully
      preserved clinical competence, only 7 patients (9 %) had partially preserved
      clinical competence and 72 patients (91 %) had completely lost clinical
      competence. All the patients with partially preserved clinical competence (9 %)
      were aware of their memory deficit. The study indicates that neuropsychological
      tests used for the assessment of executive functions are not suitable for
      investigating clinical competence. Therefore, additional and specific tools for
      the evaluation of clinical competence are necessary. Indeed, these might allow
      clinicians to identify AD patients who, despite their deficits in selected
      functions, retain their autonomy of choice as well as recognize those patients
      who should proceed to the nomination of a legal representative.

PMID- 23959533
TI  - The heat is on: a case of hyperthermia-induced posterior reversible
      encephalopathy syndrome (PRES).

PMID- 23959534
TI  - Parental reaction to early diagnosis of their children's autism spectrum
      disorder: an exploratory study.
AB  - This study explores parental reactions subsequent to receiving their child's
      autism spectrum disorder (ASD)-diagnosis. Seventy seven parents of recently
      diagnosed children participated in the Reaction to Diagnosis Interview. Within
      this group, associations between parental reaction to diagnosis, parental and
      child characteristics and prediagnostic circumstances were analysed. In a sub
      sample, the stability of reaction to diagnosis was examined. The majority of
      parents were classified as 'resolved' regarding their child's diagnosis.
      Conversely, parents of children with more severe ASD symptoms or non-Dutch
      parents were more likely to be classified as 'unresolved'. Sub-sample analysis
      revealed stability of reaction to ASD-diagnosis. The majority of parents adapted
      well to the circumstances and the care for their child. Autism severity and
      parental nationality were significant factors affecting parental reactions. Thus,
      early identification of parental reaction to children's ASD-diagnosis may aid in
      providing more tailored parental support programs.

PMID- 23959535
TI  - Strengthening the bones in primary biliary cirrhosis.

PMID- 23959536
TI  - [Mindfulness based cognitive therapy (MBCT) in patients with obsessive-compulsive
      disorder--an adaptation of the original program].
AB  - Mindfulness-based cognitive Therapy (MBCT) has shown to be effective in the
      relapse prevention and treatment of several psychiatric disorders. However, MBCT
      has not yet been applied in OCD (Obsessive-compulsive Disorder). This article
      proposes an adaptation of the eight-session group program for patients with
      residual symptoms after cognitive behavioural treatment (CBT) with exposure. It
      has proven feasible and was considered helpful by patients within the framework
      of a pilot study 1. Apart from an overview of the modified manual, OCD-specific
      elements are presented in detail and illustrated on the base of work sheets. The
      manual indicates that MBCT could be a useful supplement to CBT and is well
      applicable to the therapeutic needs of patients with OCD. 

PMID- 23959537
TI  - Accuracy of International Classification of Diseases, 9th Revision, Clinical
      Modification codes for upper gastrointestinal complications varied by position
      and age: a validation study in a cohort of nonsteroidal anti-inflammatory drugs
      users in Friuli Venezia Giulia, Italy.
AB  - PURPOSE: To validate the International Classification of Diseases, 9th Revision,
      Clinical Modification discharge codes used to identify cases of upper
      gastrointestinal complications (UGICs) in hospitals of Friuli Venezia Giulia,
      Italy. METHODS: Cohort study on the risk of UGIC in users of nonsteroidal anti
      inflammatory drugs conducted in Friuli Venezia Giulia between 2001 and 2008.
      Cases were identified through primary and secondary International Classification
      of Diseases, 9th Revision Clinical specific codes 531 (gastric ulcer), 532
      (duodenal ulcer), 533 (peptic ulcer), 534 (gastrojejunal ulcer), and nonspecific
      code 578 (gastrointestinal hemorrhage). Potential cases were confirmed through
      hospital chart review. RESULTS: The chart retrieval percentage was 98.4%.The
      positive predictive value (PPV) was 94.3% for primary codes 531 and 532, 79.5%
      for code 533, 83.1% for code 534, 40.2% for code 578. The PPV for secondary codes
      was 34.7% but increased to 88.9% and 79.2% when the primary code was for
      peritonitis or acute post-hemorrhagic anemia, respectively. Validation of
      secondary codes increased case ascertainment by 4.9%. Endoscopy confirmed 79.4%
      of cases but only 67.2% of those above age 84 years. CONCLUSIONS: The PPV was
      high for specific primary codes and moderate to low for nonspecific primary and
      secondary codes. The inclusion of confirmed cases identified by nonspecific and
      secondary codes can be of value in studies that need a complete ascertainment of
      cases occurring in the study population. In this cohort, not including these
      cases would underestimate the incidence of UGICs. A potential for case
      misclassification exists in particular in eldest ages.

PMID- 23959538
TI  - Anticonvulsant activity of fraction isolated from ethanolic extract of heartwood
      of Cedrus deodara.
AB  - The heartwood of Cedrus deodara is traditionally used for the treatment of
      neurological disorders in India. In this study, the compound 3,4-bis(3,4
      dimethoxyphenyl) furan-2,5-dione (BDFD) isolated from the ethanolic extract of C.
      deodara was evaluated for its anticonvulsant activity. The experimental studies
      were carried out in albino mice (18-22 g) and rats (180-220 g), employing
      different models of convulsions. The N-methyl-D-aspartic acid (NMDA)-induced
      lethality test and estimation of brain gamma-aminobutyric acid (GABA) were
      carried out to investigate the mechanism of action of this compound. BDFD gave
      dose-dependent protection against pentylenetetrazole (PTZ)-, pilocarpine- and 6
      Hz-induced convulsions but it could not inhibit NMDA-induced lethality. Motor
      incoordination was displayed when the BDFD dose exceeded 400 mg/kg, whereas the
      therapeutic dose was below 100 mg/kg in the PTZ, pilocarpine and 6-Hz models (39
      90 mg/kg). Furthermore, brain GABA estimation revealed that this compound
      increases the GABA level. BDFD dose levels up to 150 mg/kg did not prevent NMDA
      induced lethality, which proves its weak influence on the excitatory
      neurotransmitter glutamate. The findings of the experiments on various animal
      models clearly demonstrated that BDFD possesses anticonvulsant activity by
      enhancing inhibitory GABAminergic neurotransmission.

PMID- 23959539
TI  - Annual Medical Costs of Swedish Patients with Type 2 Diabetes Before and After
      Insulin Initiation.
AB  - INTRODUCTION: Although insulin is one of the most effective interventions for the
      treatment of type 2 diabetes, its disadvantages incur substantial medical cost.
      This study was designed to evaluate the medical costs of Swedish type 2 diabetic
      patients initiating insulin on top of metformin and/or sulfonylurea (SU), and to
      evaluate if costs before and after insulin initiation differ for patients where
      insulin is initiated above or below the recommended glycosylated hemoglobin
      (HbA1c) level (7.5%). METHODS: This was a register-based retrospective cohort
      study in which patients were identified from the Sormland county council diabetes
      register. Patients being prescribed at least one prescription of metformin and/or
      SU from 2003 to 2010, and later prescribed insulin, were included. RESULTS: One
      hundred patients fulfilled the inclusion criteria and had at least 1 year of
      follow-up. The mean age was 61 years and 59% of patients were male. Mean time
      since diagnosis was 4.1 years, and since initiation of insulin was 2.2 years. The
      mean HbA1c level at index date was 8.0%. Total mean costs for the whole cohort
      were SEK 17,230 [standard deviation (SD) 17,228] the year before insulin
      initiation, and SEK 31,656 (SD 24,331) the year after insulin initiation (p <
      0.0001). When stratifying by HbA1c level, patients with HbA1c <7.5% had total
      healthcare costs of SEK 17,678 (SD 12,946) the year before the index date and SEK
      35,747 (SD 30,411) the year after (p < 0.0001). Patients with HbA1c levels >=7.5%
      had total healthcare costs of SEK 16,918 (SD 19,769) the year before the index
      date and SEK 28,813 (SD 18,779) the year after (p < 0.0001). CONCLUSION: Despite
      the small sample size, this study demonstrates that mean annual medical costs
      almost double the year after patients are initiated on insulin. The costs
      increased the year after insulin initiation, regardless of the HbA1c level at
      initiation of insulin, and the largest increase in costs were due to increased
      filled prescriptions.

PMID- 23959540
TI  - PIAS3 activates the intrinsic apoptotic pathway in non-small cell lung cancer
      cells independent of p53 status.
AB  - Protein inhibitor of activated signal transducer and activator of transcription 3
      (STAT3) (PIAS3) is an endogenous inhibitor of STAT3 that negatively regulates
      STAT3 transcriptional activity and cell growth and demonstrates limited
      expression in the majority of human squamous cell carcinomas of the lung. In this
      study, we sought to determine whether PIAS3 inhibits cell growth in non-small
      cell lung cancer cell lines by inducing apoptosis. Our results demonstrate that
      overexpression of PIAS3 promotes mitochondrial depolarization, leading to
      cytochrome c release, caspase 9 and 3 activation and poly (ADP-ribose) polymerase
      cleavage. This intrinsic pathway activation was associated with decreased Bcl-xL
      expression and increased Noxa expression and was independent of p53 status.
      Furthermore, PIAS3 inhibition of STAT3 activity was also p53 independent.
      Microarray experiments were performed to discover STAT3-independent mediators of
      PIAS3-induced apoptosis by comparing the apoptotic gene expression signature
      induced by PIAS3 overexpression with that induced by STAT3 siRNA. The results
      showed that a subset of apoptotic genes was uniquely expressed only after PIAS3
      expression. Thus, PIAS3 may represent a promising lung cancer therapeutic target
      because of its p53-independent efficacy and its potential to synergize with Bcl-2
      targeted inhibitors. 

PMID- 23959541
TI  - Blood pressure tracking in children and adolescents.
AB  - BACKGROUND: High blood pressure is a major risk factor for cardiovascular
      disease. Blood pressure tracking could help to identify individuals with
      potential hypertension. Therefore, we have asked whether or not tracking was of
      predictive value for the development of hypertension in early life. METHODS:
      Blood pressure was routinely measured in 13,261 children and adolescents in
      outpatient clinics as well as during hospitalization. In one analysis, 568
      individuals with elevated and normotensive blood pressure values were evaluated
      after 2, 4, and 6 years of follow-up. In a second analysis, 2,157 individuals
      with normotensive blood pressure were examined in a paired t test. RESULTS: The
      follow-up analysis showed a significant tracking effect. However, the Pearson
      correlation coefficients of the systolic and diastolic blood pressure standard
      deviation scores (SDS) decreased over time. Upon the follow-up after 6 years,
      35.6 % of the children and adolescents with elevated blood pressure values
      remained in the elevated range group. Of the children within the normotensive
      blood pressure range, 80.4 % remained normotensive after 6 years. Children with
      normotensive blood pressure showed a stronger tracking than those who had had one
      hypertensive blood pressure reading. Children with higher body mass index (BMI)
      at follow-up changed blood pressure SDS track from initially normal to higher
      blood pressure values. CONCLUSIONS: Blood pressure tracking in children and
      adolescents is moderate. We conclude that the predictive power of a single
      hypertensive blood pressure measurement during a single visit is rather small,
      and thus repetitive measurements across several consecutive visits are necessary.

PMID- 23959542
TI  - Molecular characterization of measles viruses in Turkey (2010-2011): first report
      of genotype D9 involved in an outbreak in 2011.
AB  - Genetic characterization of measles viruses (MVs) combined with acquisition of
      epidemiologic information is essential for measles surveillance programs used in
      determining transmission pathways. This study describes the molecular
      characterization of 26 MV strains (3 from 2010, 23 from 2011) obtained from urine
      or throat swabs harvested from patients in Turkey. MV RNA samples (n = 26) were
      subjected to sequence analysis of 450 nucleotides comprising the most variable C
      terminal region of the nucleoprotein (N) gene. Phylogenetic analysis revealed 20
      strains from 2011 belonged to genotype D9, 3 to D4, 2 strains from 2010 to
      genotype D4 and 1 to genotype B3. This study represents the first report
      describing the involvement of MV genotype D9 in an outbreak in Turkey. The
      sequence of the majority of genotype D9 strains was identical to those identified
      in Russia, Malaysia, Japan, and the UK. Despite lack of sufficient epidemiologic
      information, the presence of variants observed following phylogenetic analysis
      suggested that exposure to genotype D9 might have occurred due to importation
      more than once. Phylogenetic analysis of five genotype D4 strains revealed the
      presence of four variants. Epidemiological information and phylogenetic analysis
      suggested that three genotype D4 strains and one genotype B3 strain were
      associated with importation. This study suggests the presence of pockets of
      unimmunized individuals making Turkey susceptible to outbreaks. Continuing
      molecular surveillance of measles strains in Turkey is essential as a means of
      acquiring epidemiologic information to define viral transmission patterns and
      determine the effectiveness of measles vaccination programs designed to eliminate
      this virus.

PMID- 23959543
TI  - Sex and age differences in the relation of depressive symptoms with blood
      pressure.
AB  - BACKGROUND: Longitudinal associations between depressive symptoms and blood
      pressure have been inconsistent. Most studies have examined incident hypertension
      as an outcome, and few have examined effect modification. METHODS: This study
      examined moderating influences of sex and age on coincident trajectories of
      depressive symptoms and blood pressure among 2,087 participants from the
      Baltimore Longitudinal Study of Aging (aged 19-97 years; 53% men; 74% white).
      Participants underwent clinical blood pressure measurement and completed the
      Center for Epidemiological Studies-Depression (CES-D) scale on up to 14 occasions
      (mean = 3.8; SD = 2.6) over up to 29 years (mean = 7.8; SD = 6.4). CES-D was log
      transformed (CES-D(log)) for analyses. RESULTS: Mixed-effects regression revealed
      that prospective relations of CES-D(log) to diastolic blood pressure differed by
      age in women (b = 0.095; P = 0.001) but not men; greater CES-D(log) attenuated
      the expected age-related decline in diastolic blood pressure. Across all testing
      sessions, greater CES-D(log) was associated significantly with higher average
      systolic blood pressure for women (b = 2.238; P = 0.006) but not men. Age
      stratified analyses showed that greater CES-D(log) was associated significantly
      with higher average systolic (b = 3.348; P = 0.02) and diastolic (b = 1.730; P <
      0.03) blood pressure for older adults (>=58.8 years at first visit). In the
      younger age cohort, sex moderated the relation of CES-D(log) to systolic blood
      pressure (b = -3.563; P = 0.007); greater CES-D(log) in women, but lesser CES
      D(log) in men, was associated with higher systolic blood pressure. CONCLUSIONS:
      Results demonstrate sex and age differences in the relation between depressive
      symptoms and blood pressure. Findings suggest the potential importance of
      preventing, detecting, and lowering depressive symptoms to prevent hypertension
      among women and older adults.

PMID- 23959544
TI  - The effects of amlodipine and S(-)-amlodipine on vascular endothelial function in
      patients with hypertension.
AB  - BACKGROUND: Amlodipine has been shown to improve vascular endothelial function in
      hypertensive patients, but whether S(-)-amlodipine has a similar effect remains
      controversial. This study compared the effects of amlodipine and S(-)-amlodipine
      on vascular endothelial function in hypertensive patients and investigated
      relevant mechanisms of action in cell culture. METHODS: Twenty-four patients with
      essential hypertension received amlodipine and S(-)-amlodipine for 6 weeks in a
      randomized, crossover study. Associated flow-mediated dilation (FMD), nitric
      oxide (NO), and endothelial nitric oxide synthase (eNOS) levels were determined.
      NO levels were measured after exposure of human umbilical vein endothelial cells
      (HUVECs) to amlodipine, S(-)-amlodipine, the eNOS inhibitor N w-nitro-L-arginine
      (L-NA), and the Protein Kinase C (PKC) inhibitor Ro 31-8220. Phosphorylation
      levels of Ser(1177) and Thr(495) in eNOS were determined after exposure to
      amlodipine, S(-)-amlodipine, and Ro 31-8220. RESULTS: FMD, NO, and eNOS levels
      significantly improved after treatment with amlodipine and S(-)-amlodipine. The
      levels were all higher with amlodipine, although the between-treatment difference
      was not statistically significant. Amlodipine and S(-)-amlodipine significantly
      increased NO levels in cultured HUVECs, but increases in NO levels were more
      marked with amlodipine. Western blot assay showed that both amlodipine and Ro31
      8220 induced Ser(1177) phosphorylation and weakened Thr(495) phosphorylation in
      eNOS. S(-)-amlodipine had no similar effects. Amlodipine, but not S(-)
      amlodipine, decreased the PKC phosphorylation in a time-dependent manner.
      CONCLUSIONS: Amlodipine and S(-)-amlodipine can both improve endothelial function
      in hypertensive patients. Amlodipine has greater potential for vascular
      endothelial protection than S(-)-amlodipine. It affects eNOS phosphorylation at
      Ser(1177) and Thr(495) by the PKC pathway, further enhancing eNOS activation.

PMID- 23959545
TI  - Prognosis for recovery after injurious falls: clinical and policy implications of
      varying definitions of recovery.

PMID- 23959546
TI  - Resting heart rate, vagal tone, and reactive and proactive aggression in Chinese
      children.
AB  - Abundant research conducted in Western contexts has shown that biological risk
      factors such as low resting heart rate (HR) might be related to childhood
      aggression. However, it was unclear (1) how resting HR, as well as other markers
      of cardiac functions such as resting vagal tone, may be related to subtypes of
      aggression such as reactive and proactive aggression, and (2) whether the HR
      aggression relation can be replicated in non-Western contexts. Therefore, this
      study examined the concurrent and prospective relations between resting HR, vagal
      tone, and Chinese children's reactive and proactive aggression. Participants were
      183 children (M age=7.64 years, 91 girls) recruited from an elementary school in
      Zhenjiang, PRC. Children's resting HR and vagal tone were assessed in the second
      grade (T1). Teachers rated children's reactive and proactive aggression in the
      second (T1) and fourth grade (T2). Results showed that lower resting HR at T1 was
      associated with higher reactive and proactive aggression at T1 and T2, and higher
      vagal tone was associated with lower HR, which in turn was related to higher
      reactive and proactive aggression at T1 and T2. Lower vagal tone was directly
      related to higher reactive but not proactive aggression at T1 and T2, whereas
      lower HR was related to higher reactive aggression at T2 for children with low or
      moderate vagal tone but was not for children with high vagal tone. These
      psychophysiological findings from a non-Western context add additional support
      for both similarities and differences between reactive and proactive aggression
      in childhood.

PMID- 23959547
TI  - Connecting tubule glomerular feedback in hypertension.
AB  - In Dahl salt-sensitive rats (Dahl SS), glomerular capillary pressure increases in
      response to high salt intake and this is accompanied by significant glomerular
      injury compared with spontaneously hypertensive rats with similar blood pressure.
      Glomerular capillary pressure is controlled mainly by afferent arteriolar
      resistance, which is regulated by the vasoconstrictor tubule glomerular feedback
      (TGF) and the vasodilator connecting TGF (CTGF). We hypothesized that Dahl SS
      have a decreased TGF response and enhanced TGF resetting compared with
      spontaneously hypertensive rats, and that these differences are attributable in
      part to an increase in CTGF. In vivo, using micropuncture we measured stop-flow
      pressure (a surrogate of glomerular capillary pressure). TGF was calculated as
      the maximal decrease in stop-flow pressure caused by increasing nephron
      perfusion, TGF resetting as the attenuation in TGF induced by high salt diet, and
      CTGF as the difference in TGF response before and during CTGF inhibition with
      benzamil. Compared with spontaneously hypertensive rats, Dahl SS had (1) lower
      TGF responses in normal (6.6+/-0.1 versus 11.0+/-0.2 mm Hg; P<0.001) and high
      salt diets (3.3+/-0.1 versus 10.1+/-0.3 mm Hg; P<0.001), (2) greater TGF
      resetting (3.3+/-0.1 versus 1.0+/-0.3 mm Hg; P<0.001), and (3) greater CTGF
      (3.4+/-0.4 versus 1.2+/-0.1 mm Hg; P<0.001). We conclude that Dahl SS have lower
      TGF and greater CTGF than spontaneously hypertensive rats, and that CTGF
      antagonizes TGF. Furthermore, CTGF is enhanced by a high-salt diet and
      contributes significantly to TGF resetting. Our findings may explain in part the
      increase in vasodilatation, glomerular capillary pressure, and glomerular damage
      in SS hypertension during high salt intake. 

PMID- 23959548
TI  - Effect of renal denervation on neurohumoral activation triggering atrial
      fibrillation in obstructive sleep apnea.
AB  - Obstructive sleep apnea is characterized by repetitive collapses of the upper
      airway, negative thoracic pressure periods, and intermittent hypoxia, stimulating
      the autonomic nervous system. The increased sympathetic drive during obstructive
      sleep apnea results in postapneic blood pressure rises and neurohumoral
      activation potentially involved in the initiation and progression to permanent
      atrial fibrillation (AF). In a pig model mimicking obstructive sleep apnea, we
      studied the effects of repetitive obstructive respiratory events for 4 hours on
      the occurrence of spontaneous AF episodes, postapneic blood pressure rises, and
      neurohumoral activation. In addition, renal sympathetic denervation was performed
      to investigate the impact of the sympathetic nervous system. Repetitive
      obstructive respiratory events caused pronounced postapneic blood pressure rises,
      prolonged duration of spontaneous AF episodes triggered by spontaneous atrial
      beats, and increased plasma renin activity and aldosterone concentrations. This
      was associated with increased nicotinamide adenine dinucleotide phosphate-oxidase
      activity, reduced antioxidative capacity, and elevated expression of connective
      tissue growth factor, a redox-sensitive mediator of fibrosis. Renal sympathetic
      denervation inhibited postapneic blood pressure rises and decreased plasma renin
      activity and aldosterone concentrations. The occurrence and duration of
      spontaneous AF were reduced comparable with a combined pharmacological blockade
      of angiotensin receptor and beta-adrenoceptor. Increased atrial oxidative stress,
      together with the activation of profibrotic pathways and intermittent hypoxia,
      was not attenuated after renal sympathetic denervation. Repetitive obstructive
      respiratory events triggered spontaneous AF, increased atrial oxidative stress,
      and activated profibrotic pathways in the atrium. Renal sympathetic denervation
      reduced spontaneous AF and postapneic blood pressure rises by combined reduction
      of sympathetic drive and components of the circulating renin-angiotensin system.
      However, the generation of atrial oxidative stress was not modulated. 

PMID- 23959550
TI  - Prognostic relevance of blood pressure variability: role of long-term and very
      long-term blood pressure changes.

PMID- 23959549
TI  - Diminazene aceturate enhances angiotensin-converting enzyme 2 activity and
      attenuates ischemia-induced cardiac pathophysiology.
AB  - Angiotensin-converting enzyme 2 (ACE2) plays a critical role against myocardial
      infarction (MI). We hypothesized that activation of intrinsic ACE2 would be
      protective against ischemia-induced cardiac pathophysiology. Diminazene aceturate
      (DIZE), a small molecule ACE2 activator, has been used to evaluate this
      hypothesis. DIZE (15 mg/kg per day, s.c.) was injected 2 days before MI surgery
      and continued throughout the study period. MI rats showed a 62% decrease in
      fractional shortening (%; control, 51.1+/-3.2; DIZE alone, 52.1+/-3.2; MI, 19.1+/
      3.0), a 55% decrease in contractility (dP/dtmax mm Hg/s; control, 9480+/-425.3;
      DIZE alone, 9585+/-597.4; MI, 4251+/-657.7), and a 27% increase in ventricular
      hypertrophy (mg/mm; control, 26.5+/-1.5; DIZE alone, 26.9+/-1.4; MI, 33.4+/-1.1).
      DIZE attenuated the MI-induced decrease in fractional shortening by 89%, improved
      dP/dtmax by 92%, and reversed ventricular hypertrophy by 18%. MI also
      significantly increased ACE and angiotensin type 1 receptor levels but decreased
      ACE2 activity by 40% (control, 246.2+/-25.1; DIZE alone, 254.2+/-20.6; MI,
      148.9+/-29.2; RFU/min), which was reversed by DIZE treatment. Thus, DIZE
      treatment decreased the infarct area, attenuated LV remodeling post-MI, and
      restored normal balance of the cardiac renin-angiotensin system. In addition,
      DIZE treatment increased circulating endothelial progenitor cells, increased
      engraftment of cardiac progenitor cells, and decreased inflammatory cells in peri
      infarct cardiac regions. All of the beneficial effects associated with DIZE
      treatment were abolished by C-16, an ACE2 inhibitor. Collectively, DIZE and DIZE
      like small molecules may represent promising new therapeutic agents for MI. 

PMID- 23959551
TI  - CTGF a tubular twist on an old theme.

PMID- 23959552
TI  - Gasotransmitters: a solution for the therapeutic dilemma in preeclampsia?

PMID- 23959553
TI  - Blood pressure rhythmicity and visceral fat in children with hypertension.
AB  - Primary hypertension is associated with disturbed activity of the sympathetic
      nervous system and altered blood pressure rhythmicity. We analyzed changes in
      cardiovascular rhythmicity and its relation with target organ damage during 12
      months of antihypertensive treatment in 50 boys with hypertension (median, 15.0
      years). The following parameters were obtained before and after 12 months of
      antihypertensive treatment: 24-hour ambulatory blood pressure, left ventricular
      mass, carotid intima-media thickness, and MRI for visceral and subcutaneous
      adipose tissue. Amplitudes and acrophases of mean arterial pressure and heart
      rate rhythms were obtained for 24-, 12-, and 8-hour periods. After 1 year of
      treatment, 68% of patients were normotensive, and left ventricular mass and
      carotid intima-media thickness decreased in 60% and 62% of patients,
      respectively. Blood pressure and heart rate rhythmicity patterns did not change.
      Changes in blood pressure amplitude correlated with the decrease of waist
      circumference (P=0.035). Moreover, the decrease of visceral fat correlated with
      the decrease of 24-hour mean arterial pressure and heart rate acrophases (both
      P<0.05). There were no differences in changes of blood pressure and heart rate
      rhythms between patients who achieved or did not achieve normotension and
      regression of left ventricular mass and carotid intima-media thickness. It was
      concluded that abnormal cardiovascular rhythmicity persists in children with
      primary hypertension despite effective antihypertensive treatment, which suggests
      that it may be the primary abnormality. The correlation between changes in
      cardiovascular rhythmicity and visceral obesity may indicate that the visceral
      fat plays an important role in the sympathetic activity of adolescents with
      hypertension. 

PMID- 23959554
TI  - Adiposity, the sympathetic nervous system, and childhood primary hypertension.

PMID- 23959555
TI  - Blood pressure in relation to interactions between sodium dietary intake and
      renal handling.
AB  - There is abundant evidence that sodium intake is related to blood pressure.
      However, the relationship varies between individuals and is probably determined
      by renal sodium handling. We investigated clinic and ambulatory blood pressure in
      relation to interactions between sodium dietary intake and renal handling, as
      assessed by 24-hour urinary sodium excretion and endogenous lithium clearance,
      respectively. We calculated fractional excretion of lithium and fractional distal
      reabsorption rate of sodium, as markers of proximal and distal sodium handling,
      respectively. The 766 subjects included 379 men and 478 ambulatory hypertensive
      patients. They were never treated (n=697) or did not take antihypertensive
      medication for >=2 weeks (n=69). In adjusted analyses, none of the associations
      of urinary sodium excretion, fractional excretion of lithium, and fractional
      distal reabsorption rate of sodium with clinic or ambulatory blood pressure were
      statistically significant (P>=0.09). However, there was significant (P=0.01)
      interaction between urinary sodium excretion and fractional excretion of lithium
      in relation to nighttime diastolic blood pressure. In tertile 3 but not tertiles
      1 and 2 of fractional excretion of lithium, nighttime diastolic pressure was
      positively associated with urinary sodium excretion (P=0.03). However, nighttime
      diastolic pressure was higher in tertile 1 than tertile 3 of fractional excretion
      of lithium (+2.0 mm Hg; P=0.01), especially in the bottom tertile of urinary
      sodium excretion (+4.9 mm Hg; P<0.001). Similar trends were observed for
      nighttime systolic pressure and clinic and 24-hour diastolic pressure. In
      conclusion, sodium dietary intake and proximal tubular handling interact to be
      associated with blood pressure. 

PMID- 23959556
TI  - Call for a re-evaluation of the American Heart Association's standpoint
      concerning device-guided slow breathing using the RESPeRATE device.

PMID- 23959557
TI  - Lowered magnesium in hypertension.

PMID- 23959558
TI  - Knockdown of the hypertension-associated gene NOSTRIN alters glomerular barrier
      function in zebrafish (Danio rerio).
AB  - Hypertension is one of the major risk factors for chronic kidney disease. Using
      quantitative trait loci analysis, we identified the gene of the F-BAR protein
      NOSTRIN in the center of an overlapping region in rat and human quantitative
      trait loci that are associated with hypertension. Immunohistochemical analysis
      revealed a predominantly podocytic expression pattern of NOSTRIN in human and
      mouse glomeruli. Further, NOSTRIN colocalizes with cell-cell contact-associated
      proteins beta-catenin and zonula occludens-1 and interacts with the slit-membrane
      associated adaptor protein CD2AP. In zebrafish larvae, knockdown of nostrin
      alters the glomerular filtration barrier function, inducing proteinuria and
      leading to ultrastructural morphological changes on the endothelial and
      epithelial side and of the glomerular basement membrane of the glomerular
      capillary loop. We conclude that NOSTRIN expression is an important factor for
      the integrity of the glomerular filtration barrier. Disease-related alteration of
      NOSTRIN expression may not only affect the vascular endothelium and, therefore,
      contribute to endothelial cell dysfunction but might also contribute to the
      development of podocyte disease and proteinuria. 

PMID- 23959559
TI  - Circulating endothelin-1 alters critical mechanisms regulating cerebral
      microcirculation.
AB  - Endothelin-1 (ET1) is a potent vasoconstrictor peptide implicated in the
      cerebrovascular alterations occurring in stroke, subarachnoid hemorrhage, and
      brain trauma. Brain or circulating levels of ET1 are elevated in these conditions
      and in risk factors for cerebrovascular diseases. Most studies on the
      cerebrovascular effects of ET1 have focused on vascular smooth muscle
      constriction, and little is known about the effect of the peptide on
      cerebrovascular regulation. We tested the hypothesis that ET1 increases
      cerebrovascular risk by disrupting critical mechanisms regulating cerebral blood
      flow. Male C57Bl6/J mice equipped with a cranial window were infused
      intravenously with vehicle or ET1, and somatosensory cortex blood flow was
      assessed by laser Doppler flowmetry. ET1 infusion increased mean arterial
      pressure and attenuated the blood flow increase produced by neural activity
      (whisker stimulation) or neocortical application of the endothelium-dependent
      vasodilator acetylcholine but not A23187. The cerebrovascular effects of ET1 were
      abrogated by the ET(A) receptor antagonist BQ123 and were not related to vascular
      oxidative stress. Rather, the dysfunction was dependent on Rho-associated protein
      kinase activity. Furthermore, in vitro studies demonstrated that ET1 suppresses
      endothelial nitric oxide (NO) production, assessed by its metabolite nitrite, an
      effect associated with Rho-associated protein kinase-dependent changes in the
      phosphorylation state of endothelial NO synthase. Collectively, these novel
      observations demonstrate that increased ET1 plasma levels alter key regulatory
      mechanisms of the cerebral circulation by modulating endothelial NO synthase
      phosphorylation and NO production through Rho-associated protein kinase. The ET1
      induced cerebrovascular dysfunction may increase cerebrovascular risk by lowering
      cerebrovascular reserves and increasing the vulnerability of the brain to
      cerebral ischemia.

PMID- 23959560
TI  - Increased renal epithelial na channel expression and activity correlate with
      elevation of blood pressure in spontaneously hypertensive rats.
AB  - Elevation of blood pressure with age is one of the hallmarks of hypertension in
      both males and females. This study examined transcriptomic profiles in the kidney
      of 12-, 40-, and 80-week-old spontaneously hypertensive rats and 4 recombinant
      inbred strains in search for functional genetic elements supporting temporal
      dynamics of blood pressure elevation. We found that both in males and females of
      spontaneously hypertensive rats and hypertensive recombinant inbred strains age
      dependent blood pressure increment was accompanied by 50% heightened expression
      of epithelial sodium channel beta- and gamma-subunits. Epithelial sodium channel
      subunit expression correlated positively with blood pressure but correlated
      negatively with renin expression. Increased epithelial sodium channel activity
      was observed in cultured epithelial cells isolated from the kidney medulla of 80
      week-old spontaneously hypertensive rats but not in age-matched normotensive
      Wistar Kyoto. This difference remained evident after 24-hour treatment with
      aldosterone. 22Na uptake in the perfused kidney medulla was increased whereas the
      urinary Na/K ratio was decreased in old spontaneously hypertensive rats compared
      with normotensive controls. The difference was eliminated by the administration
      of epithelial sodium channel inhibitor benzamil. Observations in recombinant
      inbred strains representing various mixtures of parental hypertensive and
      normotensive genomes suggest that Scnn1g and Scnn1b genes themselves are not
      implicated in heightened expression and that the increased expression is neither
      secondary nor required for a partial elevation of blood pressure in contrast to
      spontaneously hypertensive rats. We suggest that spontaneously hypertensive rats
      display an intact negative feed-back between renin-angiotensin-system and
      epithelial Na channel activity whose upregulated expression is supported by a yet
      unknown mechanism. 

PMID- 23959561
TI  - Long-term and ultra long-term blood pressure variability during follow-up and
      mortality in 14,522 patients with hypertension.
AB  - Recent evidence indicates that long-term visit-to-visit blood pressure
      variability (BPV) may be an independent cardiovascular risk predictor. The
      implication of this variability in hypertension clinical practice is unclear. BPV
      as average real variability (ARV) was calculated in 14,522 treated patients with
      hypertension in 4 time frames: year 1 (Y1), years 2 to 5 (Y2-5), years 5 to 10
      (Y5-10), and years >10 (Y10+) from first clinic visit. Cox proportional hazards
      models for cause-specific mortality were used in each time frame separately for
      long-term BPV, across time frames based on ultra long-term BPV, and within each
      time frame stratified by mean BP. ARV in systolic blood pressure (SBP), termed
      ARV(SBP), was higher in Y1 (21.3+/-11.9 mm Hg) in contrast to Y2-5 (17.7+/-9.9 mm
      Hg), Y5-10 (17.4+/-9.6 mm Hg), and Y10+ (16.8+/-8.5 mm Hg). In all time frames,
      ARV(SBP) was higher in women (P<0.01) and in older age (P<0.001), chronic kidney
      disease (P<0.01), and prevalent cardiovascular disease (P<0.01). Higher long-term
      and ultra long-term BPV values were associated with increased mortality (all
      cause, cardiovascular, and noncardiovascular mortality; P for trend, <0.001).
      This relationship was also evident in subgroups with mean SBP<140 mm Hg in all
      time frames. Monitoring BPV in clinical practice may facilitate risk reduction
      strategies by identifying treated hypertensive individuals at high risk,
      especially those with BP within the normal range.

PMID- 23959562
TI  - Hypertension guidelines: more challenges highlighted by Europe.

PMID- 23959564
TI  - Selective detection of guanosine-5'-triphosphate and iodide by fluorescent
      benzimidazolium-based cyclophanes.
AB  - New fluorescent benzimidazolium-based receptors selectively display the effective
      fluorescence quenching effect for biologically important anions, GTP and I(-), in
      aqueous solution of physiological pH 7.4. These affinities can be attributed to
      the strong ionic H-bonding along with additional interactions of fluorophore
      moieties with the nucleic base of GTP and I(-). 

PMID- 23959563
TI  - Bone strength and structural deficits in children and adolescents with a distal
      forearm fracture resulting from mild trauma.
AB  - Although distal forearm fractures (DFFs) are common during childhood and
      adolescence, it is unclear whether they reflect underlying skeletal deficits or
      are simply a consequence of the usual physical activities, and associated trauma,
      during growth. Therefore, we examined whether a recent DFF, resulting from mild
      or moderate trauma, is related to deficits in bone strength and cortical and
      trabecular bone macro- and microstructure compared with nonfracture controls.
      High-resolution peripheral quantitative computed tomography was used to assess
      micro-finite element-derived bone strength (ie, failure load) and to measure
      cortical and trabecular bone parameters at the distal radius and tibia in 115
      boys and girls with a recent (<1 year) DFF and 108 nonfracture controls aged 8 to
      15 years. Trauma levels (mild versus moderate) were assigned based on a validated
      classification scheme. Compared with sex-matched controls, boys and girls with a
      mild-trauma DFF (eg, fall from standing height) showed significant deficits at
      the distal radius in failure load (-13% and -11%, respectively; p < 0.05) and had
      higher ("worse") fall load-to-strength ratios (both +10%; p < 0.05 for boys and p
      = 0.06 for girls). In addition, boys and girls with a mild-trauma DFF had
      significant reductions in cortical area (-26% and -23%, respectively; p < 0.01)
      and cortical thickness (-14% and -13%, respectively; p < 0.01) compared with
      controls. The skeletal deficits in the mild-trauma DFF patients were generalized,
      as similar changes were present at the distal tibia. By contrast, both boys and
      girls with a moderate-trauma DFF (eg, fall from a bicycle) had virtually
      identical values for all of the measured bone parameters compared with controls.
      In conclusion, DFFs during growth have two distinct etiologies: those owing to
      underlying skeletal deficits leading to fractures with mild trauma versus those
      owing to more significant trauma in the setting of normal bone strength.

PMID- 23959565
TI  - Determinants and prognostic value of cardiovascular autonomic function in
      coronary artery disease patients with and without type 2 diabetes.
AB  - OBJECTIVE Cardiovascular autonomic dysfunction is a common finding among patients
      with coronary artery disease (CAD) and type 2 diabetes (T2D). The reasons and
      prognostic value of autonomic dysfunction in CAD patients with T2D are not well
      known. RESEARCH DESIGN AND METHODS We examined the association between heart rate
      recovery (HRR), 24-h heart rate (HR) variability (SD of normal R-R interval
      [SDNN]), and HR turbulence (HRT), and echocardiographic parameters, metabolic,
      inflammatory, and coronary risk variables, exercise capacity, and the presence of
      T2D among 1,060 patients with CAD (mean age 67 +/- 8 years; 69% males; 50%
      patients with T2D). Second, we investigated how autonomic function predicts a
      composite end point of cardiovascular death, acute coronary event, stroke, and
      hospitalization for heart failure during a 2-year follow-up. RESULTS In multiple
      linear regression model, exercise capacity was a strong predictor of HRR (R =
      0.34, P < 0.001), SDNN (R = 0.33, P < 0.001), and HRT (R = 0.13, P = 0.001). In
      univariate analyses, a composite end point was predicted by reduced HRR (hazard
      ratio 1.7 [95% CI 1.1-2.6]; P = 0.020), reduced SDNN (2.0 [95% CI 1.2-3.1]; P =
      0.005), and blunted HRT (2.1 [1.3-3.4]; P = 0.003) only in patients with T2D.
      After multivariate adjustment, none of the autonomic markers predicted the end
      point, but high-sensitivity C-reactive protein (hs-CRP) remained an independent
      predictor. CONCLUSIONS Cardiovascular autonomic function in CAD patients is
      associated with several variables, including exercise capacity. Autonomic
      dysfunction predicts short-term cardiovascular events among CAD patients with
      T2D, but it is not as strong an independent predictor as hs-CRP. 

PMID- 23959566
TI  - Consumption of a diet low in advanced glycation end products for 4 weeks improves
      insulin sensitivity in overweight women.
AB  - OBJECTIVE High-heat cooking of food induces the formation of advanced glycation
      end products (AGEs), which are thought to impair glucose metabolism in type 2
      diabetic patients. High intake of fructose might additionally affect endogenous
      formation of AGEs. This parallel intervention study investigated whether the
      addition of fructose or cooking methods influencing the AGE content of food
      affect insulin sensitivity in overweight individuals. RESEARCH DESIGN AND METHODS
      Seventy-four overweight women were randomized to follow either a high- or low-AGE
      diet for 4 weeks, together with consumption of either fructose or glucose drinks.
      Glucose and insulin concentrations-after fasting and 2 h after an oral glucose
      tolerance test-were measured before and after the intervention. Homeostasis model
      assessment of insulin resistance (HOMA-IR) and insulin sensitivity index were
      calculated. Dietary and urinary AGE concentrations were measured (liquid
      chromatography tandem mass spectrometry) to estimate AGE intake and excretion.
      RESULTS When adjusted for changes in anthropometric measures during the
      intervention, the low-AGE diet decreased urinary AGEs, fasting insulin
      concentrations, and HOMA-IR, compared with the high-AGE diet. Addition of
      fructose did not affect any outcomes. CONCLUSIONS Diets with high AGE content may
      increase the development of insulin resistance. AGEs can be reduced by modulation
      of cooking methods but is unaffected by moderate fructose intake. 

PMID- 23959567
TI  - Cardiovascular autonomic dysfunction predicts severe hypoglycemia in patients
      with type 2 diabetes: a 10-year follow-up study.
AB  - OBJECTIVE The aim of this study was to investigate the development of severe
      hypoglycemia (SH) in the presence of cardiovascular autonomic neuropathy (CAN) in
      patients with type 2 diabetes. RESEARCH DESIGN AND METHODS From January 2001 to
      December 2002, a total of 894 patients with type 2 diabetes were enrolled. A
      cardiovascular autonomic function test (AFT) was performed using the following
      heart rate variability parameters: expiration-to-inspiration ratio, response to
      Valsalva maneuver, and standing. From the results for each of the three tests (0
      for normal, 1 for abnormal), a total AFT score of 1 was defined as early CAN, and
      an AFT score of >=2 was defined as definite CAN. RESULTS The median follow-up
      time was 9.5 years. The mean age was 54.5 +/- 10.1 years, and the mean duration
      of diabetes was 8.9 +/- 6.3 years. One hundred ninety-six patients (31.4%) showed
      an abnormal cardiovascular AFT score at baseline. Sixty-two patients (9.9%)
      experienced 77 episodes of SH (1.33 per 100 patient-years). The number of SH
      events increased as the CAN score increased (23 patients [5.4%] with normal
      score; 17 patients [17.2%] with early CAN; and 22 patients [22.7%] with definite
      CAN; P for trends < 0.001). Cox proportional hazards regression analysis revealed
      that SH was associated with definite CAN (normal vs. definite CAN: hazard ratio
      2.43 [95% CI 1.21-4.84]; P = 0.012). CONCLUSIONS Definite CAN was an independent
      prognostic factor for the development of SH in patients with type 2 diabetes. 

PMID- 23959569
TI  - Energy transfer in coumarin-sensitised lanthanide luminescence: investigation of
      the nature of the sensitiser and its distance to the lanthanide ion.
AB  - A series of lanthanide complexes [Ln(dpxCy)3](3-) have been synthesised. The
      ligands are composed of a coordinating dipicolinic acid backbone decorated with a
      polyoxyethylene arm fitted with a coumarin moiety at its extremity. The nature of
      the coumarin as well as the length of the linker have been varied. Upon
      excitation at 320 nm, the coumarin exclusively acts as an antenna while the
      dipicolinic acid core is not excited. Upon excitation below 300 nm, both parts
      are excited. With europium as a metal centre, the relaxation of the europium ion
      (intrinsic quantum yield Phi(Eu)(Eu) and radiative lifetime taur) is constant for
      all the studied ligands. Therefore, the observed differences in overall quantum
      yield (Phi(Eu)(L)) in such systems come exclusively from the variation of the
      terminal coumarin. The overall quantum yields of the studied complexes are low
      (Phi(Eu)(L) < 2% in aqueous solution). In order to rationalise the mechanism of
      the energy transfer and to improve the sensitisation efficiency (etasens), the
      distance between the coumarin sensitiser and the lanthanide centre was explored
      in solution and compared to the solid state. In the solid state, a dramatic
      effect was confirmed, with an improvement of 80% in the quantum yield Phi(Eu)(L)
      for short linkers ((-CH2CH2O-)n with n = 1 compared to n = 3). By monitoring the
      lifetime decay of the excited state of the lanthanide cation with nanosecond vs.
      microsecond time-resolved spectroscopy at low temperature, the sensitisation of
      the lanthanide ions by coumarin derivatives was demonstrated to mainly occur
      through the singlet excited state of the coumarin and not via the usual triplet
      pathway. No evidence of a different behaviour at room temperature was found by
      transient triplet-triplet absorption spectroscopy.

PMID- 23959570
TI  - Anchoring of silyl donors on a N-heterocyclic carbene through the cobalt-mediated
      silylation of benzylic C-H bonds.

PMID- 23959568
TI  - Real-time support of pediatric diabetes self-care by a transport team.
AB  - OBJECTIVE The study seeks to improve access for underserved patients via novel
      integration of Pedi-Flite (a critical care transport team) and to validate
      whether this safely enhances diabetes care and effectively expands the endocrine
      workforce. RESEARCH DESIGN AND METHODS The study retrospectively analyzed pager
      service use in a cohort of established diabetic patients (n = 979) after
      inception of Pedi-Flite support. Outcomes included incidence and severity of
      recurrent diabetic ketoacidosis (DKA) and cost savings generated from reduced
      referrals to the emergency department (ED) and on-call endocrinologist. We
      generated descriptive statistics to characterize the study population and ED
      visits for DKA and constructed logistic regression models to examine associations
      of pager use and likelihood of ED visitation and nonelective inpatient admission
      from an ED for DKA. RESULTS Pager users comprised 30% of the patient population.
      They were younger but had more established diabetes than nonusers. While pager
      users were 2.75 times more likely than nonusers to visit the ED for DKA (P <
      0.0001), their visits were less likely to lead to inpatient admissions (odds
      ratio 0.58; P < 0.02). More than half (n = 587) of all calls to the pager were
      resolved without need for further referral. Estimates suggest that 439 ED visits
      and 115 admissions were avoided at a potential cost savings exceeding 760,000
      USD. CONCLUSIONS Integration of a transport service provides a novel, cost
      effective approach to reduce disparities in diabetes care. Advantages include
      scalability, applicability to other disease areas and settings, and low added
      costs. These findings enrich an emerging evidence base for telephonic care
      management models supported by allied health personnel. 

PMID- 23959571
TI  - Effect of early intensive multifactorial therapy compared with routine care on
      self-reported health status, general well-being, diabetes-specific quality of
      life and treatment satisfaction in screen-detected type 2 diabetes mellitus
      patients (ADDITION-Europe): a cluster-randomised trial.
AB  - AIMS/HYPOTHESIS: The study aimed to examine the effects of intensive treatment
      (IT) vs routine care (RC) on patient-reported outcomes after 5 years in screen
      detected diabetic patients. METHODS: In a pragmatic, cluster-randomised, parallel
      group trial, 343 general practices in Denmark, Cambridge and Leicester (UK) and
      the Netherlands were randomised to screening for type 2 diabetes mellitus plus IT
      of multiple risk factors in people 40-69 years without known diabetes (n = 1,678
      patients) or screening plus RC (n = 1,379 patients). Practices were randomised in
      a 1:1 ratio according to a computer-generated list. Diabetes mellitus was
      diagnosed according to WHO criteria. Exclusions were: life expectancy <1 year,
      housebound, pregnant or lactating, or psychological or psychiatric problems.
      Treatment targets for IT were: HbA1c <7.0% (53 mmol/mol), BP <=135/85 mmHg,
      cholesterol <5 mmol/l in the absence of a history of coronary heart disease and
      <4.5 mmol/l in patients with cardiovascular (CV) disease; prescription of aspirin
      to people taking antihypertensive medication and, in cases of CV disease or BP
      >120/80 mmHg, ACE inhibitors were recommended. After 2003, the treatment
      algorithm recommended statins to all patients with cholesterol of >=3.5 mmol/l.
      Outcome measures were: health status (Euroqol 5 Dimensions [EQ-5D]) at baseline
      and at follow-up; and health status (36-item Short Form Health Survey [SF-36] and
      Euroquol Visual Analogue Scale [EQ-VAS]), well-being (12-item Short Form of the
      Well-Being Questionnaire), diabetes-specific quality of life (Audit of Diabetes
      Dependent Quality of Life) and satisfaction with diabetes treatment (Diabetes
      Treatment Satisfaction Questionnaire) at follow-up. At baseline, standardised
      self-report questionnaires were used to collect information. Questionnaires were
      completed at the same health assessment visit as the anthropometric and
      biochemical measurements. The patients and the staff assessing the outcomes were
      unaware of the group assignments. Participants were followed for a mean of 5.7
      years. Outcome data were available for 1,250 participants in the intensive
      treatment group (74%) and 967 participants in the routine care group (70%). The
      estimated differences in means from the four centres were pooled using random
      effects meta-analysis. Baseline EQ-5D level was used as a covariate in all
      analyses. RESULTS: EQ-5D values did not change between diagnosis and follow-up,
      with a median (interquartile range) of 0.85 (0.73-1.00) at baseline and 0.85
      (0.73-1.00) at 5 year follow-up. Health status, well-being, diabetes-specific
      quality of life and treatment satisfaction did not differ between the intensive
      treatment and routine care groups. There was some heterogeneity between centres
      (I 2 being between 13% [SF-36 physical functioning] and 73% [EQ-VAS]).
      CONCLUSIONS/INTERPRETATION: There were no differences in health status, well
      being, quality of life and treatment satisfaction between screen-detected type 2
      diabetes mellitus patients receiving intensive treatment and those receiving
      routine care. These results suggest that intensive treatment does not adversely
      affect patient-reported outcomes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov
      NCT00237549 FUNDING: ADDITION-Denmark was supported by the National Health
      Services, the Danish Council for Strategic Research, the Danish Research
      Foundation for General Practice, Novo Nordisk Foundation, the Danish Centre for
      Evaluation and Health Technology Assessment, the Diabetes Fund of the National
      Board of Health, the Danish Medical Research Council and the Aarhus University
      Research Foundation. In addition, unrestricted grants from pharmaceutical
      companies were received. ADDITION-Cambridge was supported by the Wellcome Trust,
      the Medical Research Council, the NIHR Health Technology Assessment Programme,
      National Health Service R&D support funding and the National Institute for Health
      Research. SJG received support from the Department of Health NIHR grant funding
      scheme. ADDITION-Leicester was supported by Department of Health, the NIHR Health
      Technology Assessment Programme, National Health Service R&D support funding and
      the National Institute for Health Research. ADDITION-Netherlands was supported by
      unrestricted grants from Novo Nordisk, Glaxo Smith Kline and Merck, and by the
      Julius Center for Health Sciences and Primary Care, University Medical Center,
      Utrecht.

PMID- 23959572
TI  - High frequency of autoantibodies in patients with long duration type 1 diabetes.

PMID- 23959573
TI  - Cytomegalovirus and posttransplant biliary complications: Elusive offender or
      innocent bystander?

PMID- 23959574
TI  - Rheumatoid arthritis pharmacotherapy and predictors of disease-modifying anti
      rheumatic drug initiation in the early years of biologic use in Quebec, Canada.
AB  - Disease-modifying anti-rheumatic drugs (DMARDs) are the cornerstone of rheumatoid
      arthritis (RA) pharmacotherapy and should be initiated promptly after RA
      diagnosis. We examined trends in use of traditional and biologic DMARDs, and non
      DMARD treatments, among overall RA patients, and factors associated with DMARD
      initiation in the newly diagnosed RA. RA subjects identified with the Quebec
      administrative databases were followed between January 1, 2002, and December 31,
      2008. DMARD use was characterized on November 1 of each year using cross
      sectional analyses. For a subgroup of newly diagnosed subjects, we used
      multivariable logistic regressions to identify predictors of DMARD initiation
      within 12 months of diagnosis and survival analyses to appraise time to DMARD
      initiation. A total of 37,399 subjects were included (65.8 % >=65 years; 70.5 %
      female). The percentage of subjects using any DMARDs increased over the study
      period from 41.4 % [95 % confidence interval (CI) 40.8-42.0] to 43.3 % (95 % CI
      42.7-43.9). Among newly diagnosed RA, being followed by a rheumatologist was the
      strongest predictor of DMARD initiation (odds ratio 4.31; 95 % CI 3.73-4.97).
      Care by an internist, increasing calendar year, use of NSAIDs, corticosteroids,
      or opioids, and a history of hospitalization increased the likelihood of DMARD
      initiation. Older age, female, higher comorbidity score, number of medical visits
      pre-diagnosis, care by other specialists, and the use of acetaminophen were
      inversely associated with DMARD initiation. The probability of any DMARD
      initiation at 12 months was 38.5 %. Despite the clinical practice guideline
      recommendations for earlier aggressive RA management, DMARD use appears to be
      suboptimal in Quebec.

PMID- 23959575
TI  - Chemokine receptor CCR6-dependent accumulation of gammadelta T cells in injured
      liver restricts hepatic inflammation and fibrosis.
AB  - Chronic liver injury promotes hepatic inflammation, representing a prerequisite
      for organ fibrosis. We hypothesized a contribution of chemokine receptor CCR6 and
      its ligand, CCL20, which may regulate migration of T-helper (Th)17, regulatory,
      and gamma-delta (gammadelta) T cells. CCR6 and CCL20 expression was
      intrahepatically up-regulated in patients with chronic liver diseases (n = 50),
      compared to control liver (n = 5). Immunohistochemistry revealed the periportal
      accumulation of CCR6(+) mononuclear cells and CCL20 induction by hepatic
      parenchymal cells in liver disease patients. Similarly, in murine livers, CCR6
      was expressed by macrophages, CD4 and gammadelta T-cells, and up-regulated in
      fibrosis, whereas primary hepatocytes induced CCL20 upon experimental injury. In
      two murine models of chronic liver injury (CCl4 and methionine-choline-deficient
      diet), Ccr6(-/-) mice developed more severe fibrosis with strongly enhanced
      hepatic immune cell infiltration, compared to wild-type (WT) mice. Although CCR6
      did not affect hepatic Th-cell subtype composition, CCR6 was explicitly required
      by the subset of interleukin (IL)-17- and IL-22-expressing gammadelta T cells for
      accumulation in injured liver. The adoptive transfer of WT gammadelta, but not
      CD4 T cells, into Ccr6(-/-) mice reduced hepatic inflammation and fibrosis in
      chronic injury to WT level. The anti-inflammatory function of hepatic gammadelta
      T cells was independent of IL-17, as evidenced by transfer of Il-17(-/-) cells.
      Instead, hepatic gammadelta T cells colocalized with hepatic stellate cells
      (HSCs) in vivo and promoted apoptosis of primary murine HSCs in a cell-cell
      contact-dependent manner, involving Fas-ligand (CD95L). Consistent with
      gammadelta T-cell-induced HSC apoptosis, activated myofibroblasts were more
      frequent in fibrotic livers of Ccr6(-/-) than in WT mice. CONCLUSION: gammadelta
      T cells are recruited to the liver by CCR6 upon chronic injury and protect the
      liver from excessive inflammation and fibrosis by inhibiting HSCs.

PMID- 23959577
TI  - Meniscal cysts: treatment options and algorithm.
AB  - Meniscal cysts are commonly seen in the knee. Symptomatic meniscal cysts tend to
      be located on the lateral side but magnetic resonance imaging studies indicate
      that medial cysts are more common. Meniscal cysts are commonly associated with
      horizontal meniscal tears. The arthroscopic management of symptomatic cysts
      should include debriding the horizontal meniscal tear (if nonrepairable) to fully
      decompress the cyst and the creation of a 5-mm channel from the joint into the
      cyst. If a vertical peripheral meniscal tear exists or is created, meniscal
      repair for appropriately selected cases should be performed. 

PMID- 23959578
TI  - Intraoperative nonpharmacotherapeutic blood management strategies in total knee
      arthroplasty.
AB  - Substantial amounts of perioperative blood loss occur during total knee
      arthroplasty (TKA) that may require allogeneic transfusion in more than 30% of
      patients. Increased blood loss leads to poor physical functioning, increases
      infection risks, and prolongs hospitalization, which may eventually affect the
      overall clinical outcomes of TKA. In addition, allogeneic blood transfusions are
      associated with increased risks of transfusion reactions, immunosuppression, and
      a variety of immunological reactions. These concerns have led surgeons and
      anesthesiologists to develop various strategies to conserve blood, reduce costs,
      and decrease complications related to blood transfusions. Multiple
      nonpharmacologic intraoperative blood-saving measures have been used including
      acute normovolemic hemodilution, hypotensive anesthesia, tourniquets, bipolar
      sealants, intraoperative blood salvage systems, intramedullary femoral plugs,
      computer-assisted surgery, and the use of patient-specific instrumentation.
      However, no clear protocol exists currently to help surgeons choose the
      appropriate method for blood preservation. The aim of this article was to review
      the various nonpharmacologic intraoperative blood management strategies that have
      been used in TKA and to analyze their effectiveness and potential complications
      according to current evidence. 

PMID- 23959576
TI  - The current status of tailor-made medicine with molecular biomarkers for patients
      with clear cell renal cell carcinoma.
AB  - Appropriate use of multiple reliable molecular biomarkers in the right context
      will play a role in tailormade medicine of clear cell renal cell carcinoma (RCC)
      patients in the future. A total of 11,056 patients from 53 studies were included
      in this review. The article numbers of the each evidence levels, using the
      grading system defined by the Oxford Centre for Evidence-based Medicine, in 1b,
      2a, 2b, and 3b were 5 (9%), 18 (34%), 29 (55%), and 1 (2%), respectively. The
      main goal of using biomarkers is to refine predictions of tumor progression,
      pharmacotherapy responsiveness, and cancer-specific and/or overall survival.
      Currently, carbonic anhydrase (CA9) and vascular endothelial growth factor (VEGF)
      in peripheral blood and p53 in tumor tissues are measured to predict metastasis,
      while VEGF-related proteins in peripheral blood are used to assess
      pharmacotherapy responsiveness with sunitinib. Furthermore, interleukin 8,
      osteopontin, hepatocyte growth factor, and tissue inhibitors of
      metalloproteinases-1 in peripheral blood enable assessment of responsiveness to
      pazopanib treatment. Other reliable molecular biomarkers include von Hippel
      Lindau gene alteration, hypoxia-inducible factor-1a, CA9, and survivin in tumor
      tissues and VEGF in peripheral blood for predicting cancer-specific survival. In
      the future, studies should undergo external validation for developing tailored
      management of clear cell RCC with molecular biomarkers, since individual
      institutional studies lack the generalization and consistency required to
      maintain accuracy among different patient series.

PMID- 23959580
TI  - The role of time preferences in the intergenerational transfer of smoking.
AB  - Evidence suggests that maternal and offspring smoking behaviour is correlated.
      Little is known about the mechanisms through which this intergenerational
      transfer occurs. This paper explores the role of time preferences. Although time
      preference is likely to be heritable and correlated with health investments, its
      role in the intergenerational transmission of smoking has not been explored
      previously. This is the first paper to empirically test this. Data (2002, 2003,
      2004, 2006 and 2008) from the Household, Income and Labour Dynamics in Australia
      are used. Estimates by using a pooled probit model show that there is not a
      direct effect of maternal time preference, measured in terms of financial
      planning horizon, on the likelihood that their offspring is a smoker. However,
      there is an indirect effect of maternal time preference. Sons of mothers that are
      smokers and have a shorter planning horizon are 6% more likely to smoke than if
      their mother had a longer planning horizon, and daughters of mothers that smoke
      with a shorter planning horizon are 7% more likely to smoke themselves than if
      their mother had a longer planning horizon.

PMID- 23959579
TI  - Potential roles of microglial cell progranulin in HIV-associated CNS pathologies
      and neurocognitive impairment.
AB  - Progranulin (PGRN) is a highly unusual molecule with both neuronal and microglial
      expression with two seemingly unrelated functions, i.e., as a neuronal growth
      factor and a modulator of neuroinflammation. Haploinsufficiency due to loss of
      function mutations lead to a fatal presenile dementing illness (frontotemporal
      lobar degeneration), indicating that adequate expression of PGRN is essential for
      successful aging. PGRN might be a particularly relevant factor in the
      pathogenesis of HIVencephalitis (HIVE) and HIV-associated neurocognitive
      disorders (HAND). We present emerging data and a review of the literature which
      show that cells of myeloid lineage such as macrophages and microglia are the
      primary sources of PGRN and that PGRN expression contributes to pathogenesis of
      CNS diseases. We also present evidence that PGRN is a macrophage antiviral
      cytokine. For example, PGRN mRNA and protein expression are significantly
      upregulated in brain specimens with HIVE, and in HIV infected microglia in vitro.
      Paradoxically, our preliminary CHARTER data analyses indicate that lower PGRN
      levels in CSF trended towards an association with HAND, particularly in those
      without detectable virus. Based upon these findings, we introduce the hypothesis
      that PGRN plays dual roles in modulating antiviral immunity and neuronal
      dysfunction in the context of HIV infection. In the presence of active viral
      replication, PGRN expression is increased functioning as an anti-viral factor as
      well as a neuroprotectant. In the absence of active HIV replication, ongoing
      inflammation or other stressors suppress PGRN production from
      macrophages/microglia contributing to neurocognitive dysfunction. We propose.

PMID- 23959581
TI  - A hybrid ring-opening metathesis polymerization catalyst based on an engineered
      variant of the beta-barrel protein FhuA.
AB  - A beta-barrel protein hybrid catalyst was prepared by covalently anchoring a
      Grubbs-Hoveyda type olefin metathesis catalyst at a single accessible cysteine
      amino acid in the barrel interior of a variant of beta-barrel transmembrane
      protein ferric hydroxamate uptake protein component A (FhuA). Activity of this
      hybrid catalyst type was demonstrated by ring-opening metathesis polymerization
      of a 7-oxanorbornene derivative in aqueous solution. 

PMID- 23959583
TI  - Diagnostic challenges in a case of B cell lymphoma unclassifiable with features
      intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma.
AB  - Unclassifiable B-cell lymphoma with features intermediate between diffuse large B
      cell lymphoma (DLBCL) and Burkitt lymphoma (BL) is a recently recognized category
      of mature B-cell lymphoma. This represents a heterogeneous group of diseases
      which often pose diagnostic problems in clinical practice, yet its distinction
      from DLBCL to BL is important for its therapeutic and prognostic implications. We
      report the challenging diagnostic process of a 60-year-old man. He had a CD10 and
      BCL2-positive, BCL6-negative B-cell malignancy with loss of multiple B-cell
      markers including surface immunoglobulin. The karyotype was complex and unusual,
      including t(2;18)(p12;q21), t(8;14)(q24;q32) and a derivative chromosome 22
      mimicking a Philadelphia chromosome that led to initial diagnostic confusion. A
      triple-hit gray zone B-cell lymphoma with rearrangements of MYC, BCL2, BCL6, both
      alleles of IGH and likely IGK and IGL was finally diagnosed upon additional
      fluorescence in situ hybridization (FISH) studies. His disease was nonresponsive
      to intensive combination chemotherapy and he died 4 months after presentation.
      This case illustrates the diagnostic difficulty encountered in such group of B
      cell lymphomas and emphasizes the need to integrate morphological,
      immunophenotypic and genetic data in making a diagnosis.

PMID- 23959584
TI  - Guest editorial: new basic and clinical aspects of graft-versus-host  disease:
      what can we do without ''Doc'' Brown's help?

PMID- 23959582
TI  - Graft-versus-host disease biomarkers: omics and personalized  medicine.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most
      effective form of tumor immunotherapy available to date and the frequency of
      transplants continues to increase worldwide. However, while allo-HSCT usually
      induces a beneficial graft-versus leukemia effect, a major source of morbidity
      and mortality following allo-HSCT is graft-versus-host disease (GVHD). Currently
      available diagnostic and staging tools frequently fail to identify those at
      higher risk for GVHD morbidity, treatment unresponsiveness, and death.
      Furthermore, there are shortcomings in the risk stratification of patients before
      GVHD clinical signs develop. In parallel, recent years have been characterized by
      an explosive evolution of omics technologies, largely due to technological
      advancements in chemistry, engineering, and bioinformatics. Building on these
      opportunities, plasma biomarkers have been identified and validated as promising
      diagnostic and prognostic tools for acute GVHD. This review summarizes current
      information on the types of GVHD biomarkers, the omics tools used to identify
      them, the biomarkers currently validated as acute GVHD markers, and future
      recommendations for incorporating biomarkers into new grading algorithms for risk
      stratifying patients and creating more personalized treatment courses. Future
      directions will include randomized evaluations of these biomarkers in multicenter
      prospective studies while extending on the need for biomarkers of chronic GVHD.

PMID- 23959585
TI  - Brief report: diminishing geographic variability in autism spectrum disorders
      over time?
AB  - We investigated differences in the geographic distribution of autism spectrum
      disorders (ASD) over time in central North Carolina with data from the Autism and
      Developmental Disabilities Monitoring Network. Using generalized additive models
      and geographic information systems we produced maps of ASD risk in 2002-2004 and
      2006-2008. Overall the risk of ASD increased 52.9 % from 2002-2004 to 2006-2008.
      However, the magnitude of change in risk was not uniform across the study area;
      while some areas experienced dramatic increases in ASD risk(>400 %), others
      experienced slight decreases. Generally,areas with the lowest risk in 2002-2004
      experienced the greatest increases over time. Education and outreach efforts in
      North Carolina expanded during this period, possibly contributing to the observed
      leveling of risk over time.

PMID- 23959586
TI  - Pd(0)-catalyzed benzylic arylation-oxidation of 4-methylquinazolines via sp3 C-H
      activation under air conditions.
AB  - An efficient and selective Pd(0)-catalyzed sp(3) C-H bond arylation-oxidation of
      4-methylquinazolines is reported. The method enables the introduction of
      arylketone at the benzylic position of 4-methylquinazolines without the use of an
      additional directing group, and atmospheric oxygen is used as the sole oxidant. 

PMID- 23959587
TI  - Secondary use of health information: are we asking the right question?

PMID- 23959588
TI  - The impact of a diagnosis of personality disorder on service usage  in an adult
      Community Mental Health Team.
AB  - PURPOSE: Patients with a diagnosis of personality disorder (PD) have multiple and
      diverse needs. It has been noted that individuals with personality disorder are
      high users of health care resources, especially psychiatric services, ambulance
      services and emergency departments. In addition PD has been shown to be a
      significant predictor of disability and mental health consultations independent
      of Axis I disorders and physical conditions. This study aimed to compare the
      patterns of service usage, clinical ratings of symptoms and functioning, as well
      as demographic and clinically relevant historical variables between a group of
      patients with PD and a random sample of all other patients registered with a
      South London Community Mental Health Team. METHODS: A case-control design was
      used to examine service usage patterns over a one-year period for 73 cases and 96
      controls. Diagnoses were established by clinician discussion. Clinical outcomes
      were measured with Health of the Nation Outcome Scales and Global Assessment of
      Functioning, while service use was recorded using ten variables obtained from
      case note review. RESULTS: People with a diagnosis of PD were more often white
      and had a history of abuse, particularly childhood emotional abuse. They were
      higher users of some aspects of the service as compared to controls, and had
      significantly higher severity of symptoms and poorer functioning on clinician
      rated measures. CONCLUSION: This study confirms previous findings that people
      with PD have more severe symptomatology and greater degrees of functional
      impairment when compared to those without. Community clinicians should routinely
      screen attenders to predict likely difficulties that might arise and to make
      provision for these difficulties in the treatment and management of clients.

PMID- 23959589
TI  - Prevalence, types and comorbidity of mental disorders in a Kenyan primary health
      centre.
AB  - PURPOSE: To estimate the prevalence, types and comorbidity of the most common
      mental disorders and the spread of suicide risk in a primary care practice in
      Kenya. METHODS: This was a cross-sectional descriptive study. A total of 300
      adult outpatients were randomly selected while they were consulting their general
      practitioner. The M.I.N.I. Plus interview five was used to diagnose psychiatric
      disorders and suicide risk. RESULTS: Thus, 56.3 % of the sample (n = 169)
      presented one or more psychiatric disorders. The most prevalent disorders were
      Affective (39.0 %), Anxiety (31.3 %), and Somatoform (13.0 %). Regarding specific
      disorders, the most common were Major Depressive Disorder (26.3 %), Agoraphobia
      (16.7 %), Pain Disorder (12.5 %), Generalized Anxiety Disorder (9.3 %) and
      Bipolar Disorder (9 %). We found three cases of Bulimia Nervosa (1 %); 29.7 % had
      more than one current mental disorder. Suicide risk was present in 12.7 % of
      participants. No associations were identified between socio-demographic factors
      and the presence of mental disorder. Suicide risk was higher in women and in
      patients who came from slum areas. Gastric pain was positively associated with
      presence of mental disorder. CONCLUSION: High prevalence of mental disorders and
      suicide risk calls for integrating mental health services in primary health care;
      in particular, this study highlights the importance of differentiating between
      specific types of mental disorders (which require different therapeutic
      approaches), and of diagnosing comorbidities.

PMID- 23959591
TI  - Tailoring the window sizes to control the local concentration and activity of
      (salen)Co catalysts in plugged nanochannels of SBA-15 materials.

PMID- 23959590
TI  - Traumatic events and their relative PTSD burden in Northern Ireland: a
      consideration of the impact of the 'Troubles'.
AB  - PURPOSE: Over a 30-year period in its recent history, daily life in Northern
      Ireland (NI) was characterised by civil violence, colloquially termed as the
      'Troubles'. The current report examines exposure to 29 traumatic event types and
      the associated conditional prevalence of post-traumatic stress disorder (PTSD)
      among the Northern Ireland population, with a focus on the impact of traumatic
      events that were characteristic of the NI 'Troubles'. METHOD: Results presented
      are based on analysis of data from the Northern Ireland Study of Health and
      Stress (NISHS). The NISHS is a representative epidemiological study of mental
      health among the NI adult population (N = 4,340) and part of the World Mental
      Health Survey Initiative. RESULTS: Perpetration of violence, physical assault by
      a spouse or partner and private events were the event types associated with the
      highest conditional prevalence of PTSD. Despite this elevated risk, collectively
      these events accounted for just 16.8% of the overall public burden of PTSD, given
      their low prevalence among the general population. Events that were
      characteristic of civil conflict, including unexpected death of a loved one,
      witnessing death or a dead body or someone seriously injured and being mugged or
      threatened with a weapon accounted for the highest proportion of the overall
      public health burden of PTSD (18.6, 9.4 and 7.8%, respectively). These findings
      are a feature of the higher prevalence of these events among the general
      population coupled with their moderate to above average risk of PTSD.
      CONCLUSIONS: Despite the formal end to conflict in NI in 1999, a substantial
      proportion of the adult population continue to suffer the adverse mental health
      effects of chronic trauma exposure. Given rates of recovery of PTSD in the
      absence of evidence-based treatments, it is likely that the legacy of mental ill
      health associated with conflict, if not adequately addressed, will endure for
      many years.

PMID- 23959592
TI  - Mental health affects the quality of life and recovery after liver
      transplantation.
AB  - There has been little research examining the effects of mental health before
      liver transplantation on quality of life (QOL) and recovery after
      transplantation. Therefore, the purpose of the current study was to examine how
      pretransplant depression and anxiety affect mental health, QOL, and recovery
      after transplantation. Eighty-two transplant recipients provided data when they
      were listed for transplantation and 6 months after transplantation. Pretransplant
      anxiety predicted posttransplant anxiety (P < 0.001), and there was a trend in
      predicting posttransplant depression (P = 0.06). Pretransplant depression
      predicted posttransplant depression (P = 0.03), and there was a trend in
      predicting posttransplant anxiety (P = 0.06). Additionally, pretransplant anxiety
      predicted posttransplant QOL for several domains, including Body Pain, Role
      Limitations Due to Emotional Problems, and Mental Health, as well as the Mental
      Health Composite Score (P < 0.05). However, in comparison with anxiety,
      pretransplant depression independently predicted outcomes for more QOL domains,
      which included Physical Functioning, Role Limitations Due to Physical Problems,
      General Health, Vitality, and Social Functioning, as well as the Physical
      Composite Score (P < 0.05). Patients with depression at the baseline were more
      likely to report incomplete recovery 6 months after transplantation (P < 0.001).
      With respect to baseline anxiety, there was a trend suggesting that these
      patients were also more likely to report incomplete recovery (P = 0.09). These
      findings highlight the importance of evaluating transplant candidates both before
      and after transplantation for anxiety and depressive symptoms. Once patients with
      these symptoms are identified, they can be referred for treatment, which may lead
      to better posttransplant outcomes for mental health, QOL, and recovery.

PMID- 23959593
TI  - Allele frequency distribution of 1691G >A F5 (which confers Factor V Leiden)
      across Europe, including Slavic populations.
AB  - The allele 1691A F5, conferring Factor V Leiden, is a common risk factor in
      venous thromboembolism. The frequency distribution for this allele in Western
      Europe has been well documented; but here data from Central, Eastern and South
      Eastern Europe has been included. In order to assess the significance of the
      collated data, a chi-squared test was applied, and Tukey tests and z-tests with
      Bonferroni correction were compared. RESULTS: A distribution with a North
      Southeast band of high frequency of the 1691A F5 allele was discovered with a
      pocket including some Southern Slavic populations with low frequency. European
      countries/regions can be arbitrarily delimited into low (group 1, <2.8 %, mean
      1.9 % 1691A F5 allele) or high (group 2, >=2.8 %, mean 4.0 %) frequency groups,
      with many significant differences between groups, but only one intra-group
      difference (the Tukey test is suggested to be superior to the z-tests).
      CONCLUSION: In Europe a North-Southeast band of 1691A F5 high frequency has been
      found, clarified by inclusion of data from Central, Eastern and South-Eastern
      Europe, which surrounds a pocket of low frequency in the Balkans which could
      possibly be explained by Slavic migration. There seem to be no indications of
      variation in environmental selection due to geographical location.

PMID- 23959594
TI  - Trends in fracture incidence: a population-based study over 20 years.
AB  - To assess recent trends in fracture incidence from all causes at all skeletal
      sites, we used the comprehensive (inpatient and outpatient) data resources of the
      Rochester Epidemiology Project to estimate rates for Olmsted County, MN, USA,
      residents in 2009 to 2011 compared with similar data from 1989 to 1991. During
      the 3-year study period, 2009 to 2011, 3549 residents >=50 years of age
      experienced 5244 separate fractures. The age- and sex-adjusted (to the 2010 US
      white population) incidence of any fracture was 2704 per 100,000 person-years
      (95% confidence interval [CI] 2614 to 2793) and that for all fractures was 4017
      per 100,000 (95% CI 3908 to 4127). Fracture incidence increased with age in both
      sexes, but age-adjusted rates were 49% greater among the women. Overall,
      comparably adjusted fracture incidence rates increased by 11% (from 3627 to 4017
      per 100,000 person-years; p = 0.008) between 1989 to 1991 and 2009 to 2011. This
      was mainly attributable to a substantial increase in vertebral fractures (+47%
      for both sexes combined), which was partially offset by a decline in hip
      fractures (-25%) among the women. There was also a 26% reduction in distal
      forearm fractures among the women; an increase in distal forearm fractures among
      men aged 50 years and over was not statistically significant. The dramatic
      increase in vertebral fractures, seen in both sexes and especially after age 75
      years, was attributable in part to incidentally diagnosed vertebral fractures.
      However, the fall in hip fracture incidence, observed in most age groups,
      continues the steady decline observed among women in this community since 1950.
      More generally, these data indicate that the dramatic increases in the incidence
      of fractures at many skeletal sites that were observed decades ago have now
      stabilized.

PMID- 23959595
TI  - Electronically excited states and photochemical reaction mechanisms of beta
      glucose.
AB  - Carbohydrates are important molecular components of living matter. While
      spectroscopic and computational studies have been performed on carbohydrates in
      the electronic ground state, the lack of a chromophore complicates the
      elucidation of the excited-state properties and the photochemistry of this class
      of compounds. Herein, we report on the first computational investigation of the
      singlet photochemistry of beta-glucose. It is shown that low-lying singlet
      excited states are of nsigma* nature. Our computations of the singlet vertical
      excitation energies predict absorption from 6.0 eV onward. Owing to a dense
      manifold of weakly-absorbing states, a sizable and broad absorption in the
      ultraviolet-C range arises. We have explored two types of photochemical reaction
      mechanisms: hydrogen-detachment processes for each of the five O-H groups and a C
      O ring-opening process. Both types of reactions are driven by repulsive nsigma*
      states that are readily accessible from the Franck-Condon region and lead to
      conical intersections in a barrierless fashion. We have optimized the geometries
      of the conical intersections involved in these photochemical processes and found
      that these intersections are located around 5.0 eV for the O-H hydrogen
      detachment reactions and around 4.0 eV for the C-O ring-opening reaction. The
      energies of all conical intersections are well below the computed absorption
      edge. The calculations were performed using linear-response methods for the
      computation of the vertical excitation energies and multiconfigurational methods
      for the optimization of conical intersections and the computation of energy
      profiles. 

PMID- 23959596
TI  - Meeting the challenge of predicting hepatic clearance of compounds slowly
      metabolized by cytochrome P450 using a novel hepatocyte model, HepatoPac.
AB  - Generating accurate in vitro intrinsic clearance data is an important aspect of
      predicting in vivo human clearance. Primary hepatocytes in suspension are
      routinely used to predict in vivo clearance; however, incubation times have
      typically been limited to 4-6 hours, which is not long enough to accurately
      evaluate the metabolic stability of slowly metabolized compounds. HepatoPac is a
      micropatterened hepatocyte-fibroblast coculture system that can be used for
      continuous incubations of up to 7 days. This study evaluated the ability of human
      HepatoPac to predict the in vivo clearance (CL) of 17 commercially available
      compounds with low to intermediate clearance (<12 ml/min per kg). In vitro half
      life for disappearance of each compound was converted to hepatic clearance using
      the well stirred model, with and without correction for plasma protein binding.
      Hepatic CL, using three individual donors, was accurately predicted for 10 of 17
      compounds (59%; predicted clearance within 2-fold of observed human in vivo
      clearance values). The accuracy of prediction increased to 76% (13 of 17
      compounds) with an acceptance criterion defined as within 3-fold. When
      considering only low clearance compounds (<5 ml/min per kg), which represented 10
      of the 17 compounds, the accuracy of prediction was 60% within 2-fold and 90%
      within 3-fold. In addition, the turnover of three slowly metabolized compounds
      (alprazolam, meloxicam, and tolbutamide) in HepatoPac was directly compared with
      turnover in suspended hepatocytes. The turnover of alprazolam and tolbutamide was
      approximately 2-fold greater using HepatoPac compared with suspended hepatocytes,
      which was roughly in line with the extrapolated values (correcting for the longer
      incubation time and lower cell number with HepatoPac). HepatoPac, but not
      suspended hepatocytes, demonstrated significant turnover of meloxicam. These
      results demonstrate the utility of HepatoPac for prediction of in vivo hepatic
      clearance, particularly with low clearance compounds. 

PMID- 23959597
TI  - High level of HIV-2 false positivity in KwaZulu-Natal province: a region of South
      Africa with a very high HIV-1 subtype C prevalence.
AB  - Human immunodeficiency virus 2 (HIV-2) is found predominantly in West Africa. It
      is not unlikely, however, that HIV-2 may also be found in South Africa, due to
      the influx of immigrants into this country. It is important to distinguish
      between HIV-1 and HIV-2 since the clinical courses and treatment responses of
      these viruses are different. Routine serological methods for diagnosing HIV do
      not differentiate between HIV-1 and -2 infections, while rapid tests, viral load
      quantification and PCR are HIV-type--specific. The objective of this study was to
      describe the seroprevalence and molecular epidemiology of HIV-2 in KwaZulu-Natal,
      one of the regions with the highest HIV prevalence in the world and home of the
      two largest harbors in South Africa. HIV-1 positive samples were screened for
      antibodies against HIV-2, using a rapid test. The confirmation of HIV-2 positive
      samples was done by PCR. Of the 2,123 samples screened, 319 (15%) were identified
      as positive by the rapid test. None of these samples were confirmed positive by
      PCR. To explore this discrepancy in the results, a subset (n = 52) of the rapid
      HIV-2 positive samples was subjected to Western blotting. Thirty-seven (71%) of
      these were positive, yielding an overall HIV-2 seroprevalence of 10.6%. Three out
      of 28 (10.7%) Western blot positive samples were positive by a Pepti-LAV assay.
      This discrepancy between serological and molecular confirmation may be attributed
      to non-specific or cross-reacting antibodies. The use of rapid tests and Western
      blots for HIV-2 diagnosis in South Africa should be interpreted with caution.

PMID- 23959598
TI  - The physiology of ex vitro pineapple (Ananas comosus L. Merr.  var MD-2) as CAM
      or C3 is regulated by the environmental  conditions: proteomic and transcriptomic
      profiles.
AB  - KEY MESSAGE: Proteomic and transcriptomic profiles of key enzymes were monitored
      in pineapple plants propagated under C3 and CAM-inducing metabolisms to obtain
      insight into the CAM-facultative metabolism and the relationship of CAM plants
      with oxidative stress. ABSTRACT: Pineapple is one of the most important tropical
      crops worldwide. The use of temporary immersion bioreactors for the first stages
      of pineapple propagation enables precise control of plant growth, increases the
      rate of plant multiplication, decreases space, energy and labor requirements for
      pineapple plants in commercial micropropagation. Once the plantlets are ready to
      be taken from the reactors, they are carefully acclimatized to natural
      environmental conditions, and a facultative C3/CAM metabolism in the first 2
      months of growth is the characteristic of pineapple plants, depending on
      environmental conditions. We subjected two sets of micropropagated pineapple
      plants to C3 and CAM-inducing environmental conditions, determined by light
      intensity/relative humidity (respectively 40 MUmol m-2 s-1/85 % and 260 MUmol m-2
      s-1/50 %). Leaves of pineapple plants grown under CAM-inducing conditions showed
      higher leaf thickness and more developed cuticles and hypodermic tissue.
      Proteomic profiles of several proteins, isoenzyme patterns and transcriptomic
      profiles were also measured. Five major spots were isolated and identified, two
      of them for the first time in Ananas comosus (OEE 1; OEE 2) and the other three
      corresponding to small fragments of the large subunit of Rubisco (LSU). PEPC and
      PEPCK were also detected by immunobloting of 2DE at the end of both ex vitro
      treatments (C3/CAM) during the dark period. Isoenzymes of SOD and CAT were
      identified by electrophoresis and the transcript levels of OEE 1 and CAT were
      associated with CAM metabolism in pineapple plants.

PMID- 23959599
TI  - Flavopiridol can be safely administered using a pharmacologically derived
      schedule and demonstrates activity in relapsed and refractory non-Hodgkin's
      lymphoma.
AB  - Flavopiridol is a broad cyclin-dependent kinase inhibitor (CDKI) that induces
      apoptosis of malignant lymphocytes in vitro and in murine lymphoma models. We
      conducted a Phase I dose-escalation study to determine the maximum tolerated dose
      (MTD) for single-agent flavopiridol administered on a pharmacokinetically derived
      hybrid dosing schedule to patients with relapsed and refractory non-Hodgkin's
      lymphoma. Dose was escalated independently in one of four cohorts: indolent B
      cell (Cohort 1), mantle cell (Cohort 2), intermediate-grade B-cell including
      transformed lymphoma (Cohort 3), and T-/NK-cell excluding primary cutaneous
      disease (Cohort 4). Forty-six patients were accrued. Grade 3 or 4 leukopenia was
      observed in the majority of patients (60%), but infection was infrequent. Common
      nonhematologic toxicities included diarrhea and fatigue. Biochemical tumor lysis
      was observed in only two patients, and no patients required hemodialysis for its
      management. Dose escalation was completed in two cohorts (indolent and aggressive
      B-cell). Dose-limiting toxicities were not observed, and the MTD was not reached
      in either cohort at the highest dose tested (50 mg/m(2) bolus + 50 mg/m(2)
      continuous infusion weekly for 4 consecutive weeks of a 6-week cycle). Clinical
      benefit was observed in 26% of 43 patients evaluable for response, including 14%
      with partial responses (two mantle cells, three indolent B-cells, and one diffuse
      large B-cell). The single-agent activity of this first-generation CDKI suggests
      that other agents in this class merit further study in lymphoid malignancies,
      both alone and in combination.

PMID- 23959607
TI  - Seasonality of depression referrals in older people.
AB  - Seasonal affective disorder is becoming more widely recognised as a prevalent
      mood disorder in the adult population. However, few studies have investigated the
      link between sunlight exposure and mood in the elderly. Referrals to the
      community Mental Health Care for Older People (MHCOP) in the Hackney and City
      area, were screened for the number of patients referred with depression in three
      separate years (2007, 2009 and 2011) in order to determine whether more referrals
      were made to the service during darker months of the year (October to March) than
      in the lighter months of the year (April to September). When data from the three
      years was combined, we found no significant increase in the number of referrals
      to the MHCOP in the darker months (Chi squared value 1.375, p value (2 tailed)
      0.2409). We observed no statistically significant seasonal pattern of referrals,
      this suggests that depression in older people is not more prevalent in darker
      months of the year. 

PMID- 23959606
TI  - Neural stem cell apoptosis after low-methylmercury exposures in postnatal
      hippocampus produce persistent cell loss and adolescent memory deficits.
AB  - The developing brain is particularly sensitive to exposures to environmental
      contaminants. In contrast to the adult, the developing brain contains large
      numbers of dividing neuronal precursors, suggesting that they may be vulnerable
      targets. The postnatal day 7 (P7) rat hippocampus has populations of both mature
      neurons in the CA1-3 region as well as neural stem cells (NSC) in the dentate
      gyrus (DG) hilus, which actively produce new neurons that migrate to the granule
      cell layer (GCL). Using this well-characterized NSC population, we examined the
      impact of low levels of methylmercury (MeHg) on proliferation, neurogenesis, and
      subsequent adolescent learning and memory behavior. Assessing a range of
      exposures, we found that a single subcutaneous injection of 0.6 ug/g MeHg in P7
      rats induced caspase activation in proliferating NSC of the hilus and GCL. This
      acute NSC death had lasting impact on the DG at P21, reducing cell numbers in the
      hilus by 22% and the GCL by 27%, as well as reductions in neural precursor
      proliferation by 25%. In contrast, non-proliferative CA1-3 pyramidal neuron cell
      number was unchanged. Furthermore, animals exposed to P7 MeHg exhibited an
      adolescent spatial memory deficit as assessed by Morris water maze. These results
      suggest that environmentally relevant levels of MeHg exposure may decrease NSC
      populations and, despite ongoing neurogenesis, the brain may not restore the
      hippocampal cell deficits, which may contribute to hippocampal-dependent memory
      deficits during adolescence.

PMID- 23959608
TI  - Measuring system of care core values in a behavioral health system of care.
AB  - The Comprehensive Services for Children and Their Families or System of Care
      (SOC) is the largest mental health project ever conducted by the US federal
      government. These programs are based on a value-driven framework that includes:
      child/youth centered and family driven practice, community-based practice, and
      culturally competent practice (Stroul and Friedman in A system of care for
      children and youth with severe emotional disturbances, Georgetown University
      Child Development Center, CASSP Technical Assistance Center, Washington, DC,
      1986). The aim of this study is to determine the extent of the adoption of SOC
      values by families, system partners, providers and community organizations in a
      countywide SOC. Using a retrospective design, data was collected through a system
      wide survey and focus groups, which asked respondents to rate the presence of SOC
      core values prior to and four years following its creation. Results suggest that
      system partners, provider staff, and families are aware of the changes that have
      occurred within the system as a result of the SOC. 

PMID- 23959609
TI  - The earlier the better?

PMID- 23959611
TI  - A novel approach for efficient extrication of overlapping  chromosomes in
      automated karyotyping.
AB  - Since the introduction of the automated karyotyping systems, segmentation and
      classification of touching and overlapping chromosomes in the metaphase images
      are major challenges. The earlier reported techniques for disentangling the
      chromosome overlaps have limited success and use only color information in case
      of multispectral imaging. Most of them are restricted to separation of single
      overlap of two chromosomes. This paper introduces a novel algorithm to extricate
      overlapping chromosomes in a metaphase image. The proposed technique uses
      Delaunay triangulation to automatically identify the number of overlaps in a
      cluster followed by the detection of the appropriate cut-points. The banding
      information on the overlapped region further resolves the set of overlapping
      chromosomes with the identified cut-points. The proposed algorithm has been
      tested with four data sets of 60 overlapping cases, obtained from publically
      available databases and private genetic labs. The experimental results provide an
      overall accuracy of 75-100 % for resolving the cluster of 1-6 overlaps.

PMID- 23959612
TI  - Long-lived radical cation salts obtained by interaction of monocyclic arenes with
      niobium and tantalum pentahalides at room temperature: EPR and DFT studies.
AB  - The 1:3 reactions of the alkoxy arenes 1,4-(MeO)2 C6 H4 and 1,4-F2 -2,5-(MeO)2 C6
      H2 with TaF5 in chloroform at 40-50  degrees C resulted in formation in about 35
      % yield of the long-lived radical cation salts [1,4-(MeO)2 C6 H4 ][Ta2 F11 ] (2
      a) and [1,4-F2 -2,5-(MeO)2 C6 H2 ][Ta2 F11 ] (2 b), respectively. The non-alkoxy
      substituted [arene][M2 X11 ] [M=Ta, X=F: arene=C6 H5 Me (2 c), 1,4-C6 H4 Me2 (2
      d), C6 H5 F (2 e), C6 H5 NO2 (2 f); M=Nb, X=F: arene=C6 H5 Me (4 a), 1,4-C6 H4
      Me2 (4 b), C6 H5 F (4 c), C6 H5 NO2 (4 d); M=Ta, X=Cl: arene=1,4-C6 H4 Me2 (5)]
      were obtained from the 3:1 reactions of MX5 with the appropriate arene in
      chloroform at temperatures in the range 40-90  degrees C. Compounds 2-5 were
      detected by EPR spectroscopy (in CHCl3 ) at room temperature, and their gas-phase
      structures were optimized by DFT calculations. Formation of the M(IV) species
      [MX4 (NCMe)2 ] [M=Ta, X=F (3 a); M=Nb, X=F (3 b); M=Ta, X=Cl (3 c)] was
      ascertained by EPR spectroscopy on solutions obtained by treatment of the
      reaction mixtures with acetonitrile. Non-selective reactions occurred upon
      combination of 1,4-F2 -2,5-(MeO)2 C6 H2 with AgNbF6 (in CH2 Cl2 ) and 1,4-(MeO)2
      C6 H4 with SbF5 . 

PMID- 23959613
TI  - Congenital anomalies at the craniovertebral junction-posterior fossa region:
      report of two cases.
AB  - BACKGROUND: Various combinations of bony and soft tissue anomalies have been
      described at the craniovertebral junction (CVJ). These include posterior fossa
      dermoids (with or without dermal sinuses) associated with Klippel-Feil anomalies
      and dermoids (no previous reports of overlying dermal sinuses) associated with
      bony anomalies. PATIENTS: Two patients with a combination of CVJ anomalies are
      described. RESULTS: Both patients had a posterior fossa dermoid, dermal sinus,
      and occipitalized C1 arch. Furthermore, one patient had a complex bony CVJ
      anomaly, and the other had a Klippel-Feil anomaly in addition. The clinical
      presentation and management are elucidated. CONCLUSIONS: Patients who present
      with any one of these lesions need to be evaluated for the existence of other
      congenital anomalies. These are complex malformations to treat.

PMID- 23959614
TI  - Parallel insertion endoscopic technique for precise catheter placement in cystic
      craniopharyngiomas.
AB  - BACKGROUND: Total removal of craniopharyngioma is the most acceptable therapeutic
      modality; however, there are cases in which radical excision is not possible. To
      reduce the cystic component volume, an Ommaya reservoir catheter can be placed
      endoscopically. However, there are certain complications and risks with this type
      of maneuver, such as misplacement of the catheter, which may result in leakage of
      cyst contents or installed fluids such as bleomycin. Thus, accurate placement of
      intracystic catheter is extremely important. PATIENTS AND METHODS: The authors
      placed Ommaya reservoir catheters running over the outer surface of a transparent
      endoscopic sheath in three cases. RESULTS: This neuroendoscopic procedure permits
      easier manipulation of the catheter and precise placement of the catheter tip.
      This technique was useful for placement of Ommaya reservoir catheters.
      CONCLUSIONS: This new technique of catheter placement with neuroendoscopy is more
      accurate, safer, and less invasive.

PMID- 23959615
TI  - Therapeutic anticoagulation after craniotomies: is the risk for secondary
      hemorrhage overestimated?
AB  - OBJECTIVE: Deep venous thrombosis (DVT) and pulmonary embolism (PE) are major
      causes of postoperative morbidity and mortality in surgery. However, there is
      neither a standardized protocol for perioperative prevention of DVT or PE in
      neurosurgery nor a consensus concerning the management of postoperative DVT or PE
      after craniotomy in the early postoperative course. METHODS: We retrospectively
      analyzed management and complications in a group of patients with postoperative
      DVT or PE after craniotomy between 2006 and 2011 to estimate the risk of
      secondary hemorrhage under therapeutic anticoagulation. The interval between time
      of craniotomy and diagnosis of PE or DVT, administered anticoagulation, and the
      appearance of a clinically relevant secondary hemorrhage were analyzed. RESULTS:
      Forty-two patients met the given criteria. Indications for surgery were
      intracranial tumors (n = 33), aneurysms (n = 5), and hematomas (n = 4). PE or DVT
      was observed between the first and the 28th postoperative day (median, fifth
      postoperative day). Therapeutic anticoagulation was performed with enoxaparin or
      heparin (according to partial thromboplastin time levels). Full heparinization
      was applied in 30 patients between the second and the 30th postoperative day
      (median, 12th postoperative day). None of these patients developed a secondary
      hemorrhage. CONCLUSION: The documented differences in the anticoagulative drug
      used, the drug's dosage, and the start of medication reflect the lack of a
      standardized protocol concerning the treatment of postoperative PE or DVT after
      craniotomy. A more aggressive management regarding the application of
      anticoagulative drugs after craniotomy may be justified considering the absence
      of clinically relevant hemorrhages in this study and the life-threatening
      potential of perioperative DVT or PE.

PMID- 23959616
TI  - [Influence of a new biocidal product on the prevalence of digital dermatitis in
      dairy cows].
AB  - OBJECTIVE: It was investigated whether usage of the biocidal product T-Hexx
      Dragonhyde (Hydromer, Branchburg, NJ, USA) could influence the prevalence of
      digital dermatitis (DD). MATERIAL AND METHODS: On a dairy farm (110 milking cows)
      48 dairy cows without lameness were selected randomly for a test group or a
      control (negative) group, respectively. A high prevalence of DD (70-80%) was
      documented over a period of 2 months, during which four examinations were made,
      with an interval of 16-21 days between each examination. The respective grade of
      the DD-lesion on the hind hoofs was documented according to a scoring scheme.
      After precleaning the claws with water, the test group passed through a hoof bath
      containing T-Hexx Dragonhyde on 2 days per week at two milking times on each day,
      whereas the claws of control animals were cleaned using only a water bath.
      Splashes contaminating the animals and the environment were documented
      photographically and evaluated. Bacteriological examinations of the water bath
      and the T-Hexx-bath were performed after increasing numbers of animals had passed
      through the baths. RESULTS: Between and within groups no statistically
      significant differences in the prevalence of DD were found. DD-lesion scoring did
      not show any difference between the groups. With increasing numbers of animals
      having passed through the water bath, there was a significant increase in colony
      forming units per millilitre and of enterobacteriaceae. In the T-Hexx Dragonhyde
      footbath, bacterial contamination remained below the detection limit at all
      times. The coloured splashes of the footbath were visible up to the level of the
      udder and teats. CONCLUSION AND CLINICAL RELEVANCE: The prevalence of DD was not
      influenced by the 2% or 4% concentration of the biocidal product in the footbath.
      Thus the microbiocidal effect of the solution did not lead to an efficient
      reduction in bacteria on the hoof. To demonstrate a potential preventive effect
      on DD, future studies would require herds with lower prevalence and a higher
      sample size. However, when applying footbaths there is the general risk of milk
      contamination or causing mastitis.

PMID- 23959617
TI  - [Repeatability of measurements of the rectal temperature and comparison of
      vaginal and rectal temperature in puerperal sows].
AB  - OBJECTIVE: Postpartum diseases of sows are economically important in the pig
      industry. They affect animal health and welfare of sows and piglets. Measuring
      rectal temperature in sows post partum is a commonly used diagnostic method to
      early detection of infectious diseases. The study consisted of five parts. The
      objective of the first four parts was to evaluate the influence of different
      factors on the measurements of rectal temperature (e.g. investigator,
      thermometer, penetration depth of the thermometer). The secondary objective of
      this study was to validate the application of a temperature logger to
      continuously measure vaginal temperature. MATERIAL AND METHODS: Thirty sows on
      the first day postpartum were used in the first four parts of the study. Rectal
      temperature was measured repeatedly by one investigator, by different
      investigators, with different thermometers and at different penetration depths.
      For the fifth part of the study 21 sows on the first day postpartum were used. A
      temperature logger was inserted in the vagina for a duration of 6 hours.
      Additionally, rectal temperature was measured. RESULTS: The data showed that
      rectal temperature can be measured repeatably (mean +/- standard deviation = 38.7
      +/- 0.1  degrees C, coefficient of variation = 0.2%). Different investigators or
      thermometers resulted in low differences (0.0  degrees C and 0.1  degrees C). The
      penetration depth of the thermometer influenced the result (difference of 0.4 
      degrees C between 5 and 10 cm). Rectal and vaginal temperatures, measured in 21
      sows, were highly correlated (r = 0.80, p < 0.01) with a mean difference of 0.3 
      degrees C. CONCLUSION AND CLINICAL RELEVANCE: Rectal temperature measurement can
      be regarded as a repeatable diagnostic method. The measurement should be
      standardized (type of thermometer, penetration depth). The measurement of vaginal
      temperature with a data logger in early puerperal sows is a possible means for a
      continuous and non-invasive monitoring of body temperature.

PMID- 23959618
TI  - [Evaluation of the efficacy of a combination therapy of an antibiotic and a NSAID
      following an experimental Haemophilus parasuis infection in nursery piglets].
AB  - OBJECTIVE: The aim of the present study was to evaluate the combination therapy
      of an antibiotic (enrofloxacine-arginine, Baytril(r) RSi) and a non-steroidal
      anti-inflammatory drug (NSAID, ketoprofen, Dinalgen(r) 60 mg/ml) against a
      Haemophilus parasuis (HPS) infection in nursery piglets. MATERIAL AND METHODS:
      Forty-eight 3-week-old pigs were divided into four groups (group 1: non-infected
      controls; group 2: HPS infection; group 3: HPS infection/Baytril(r) RSi; group 4:
      HPS infection/Baytril(r) RSi/Dinalgen(r)) and housed within the isolation
      facility. After an acclimatization period of 10 days, the piglets in groups 2-4
      were intratracheally infected with 1 x 107 colony forming units (CFU) HPS serovar
      5, whereas animals of group 1 received physiological saline. Total clinical
      scores and joint scores were calculated daily after clinical examination. Seven
      days after the infection, piglets were humanely euthanized. At necropsy,
      pathological findings on serosal surfaces were scored according to severity and
      extension. RESULTS: Group 1 had the lowest clinical and pathological scores,
      followed by groups 4, 3 and 2. Piglets treated with the combination of an
      antibiotic and an NSAID showed the lowest body temperatures (significant). The
      average daily weight gain (ADWG) was not significantly different between the
      groups, but piglets of group 4 tended to reach a higher mean ADWG (340.5 g/d)
      than animals of the non-infected group 1 (323.8 g/d), the Baytril(r) RSi-treated
      group 3 (278.0 g/d) and the positive control group 2 (247.0 g/d). Piglets of the
      positive control group (group 2) achieved the highest values in the clinical,
      joint and serositis scores. CONCLUSION: The study demonstrated that a
      simultaneous treatment with enrofloxacine-arginine (Baytril(r) RSi) and
      ketoprofen had a superior therapeutic effect compared to a single antibiotic
      treatment with Baytril(r) RSi in nursery piglets experimentally infected with
      HPS.

PMID- 23959619
TI  - [Hock lesions in dairy cows--an overview].
AB  - Hock lesions are the most common husbandry-related disease of the locomotor
      system in dairy cattle. These conditions are referred to as technopathies. The
      prevalence of tarsal lesions ranges from 40 to 70% and thus, from a welfare
      standpoint, clearly exceeds an acceptable level. These lesions usually indicate
      inadequate stall or cubicle design in dairy barns. The presence and severity of
      hock lesions are associated with lameness and other limb disorders as well as
      mastitis and reduced milk yield. Hock lesions therefore influence animal welfare
      and production. Epidemiological and behavioural studies have shown that a manure
      pack covered with straw is associated with the lowest prevalence of lesions,
      followed by sand bedding, provided that the lying space is adequate. 

PMID- 23959620
TI  - [New drugs for horses and production animals in 2012].
AB  - In 2012, two newly developed active pharmaceutical ingredients for horses and
      food producing animals were released on the German market for veterinary drug
      products. Those are the parenterally applicable first generation cephalosporin
      Cefalonium (Cepravin(r)) and the nonsteroidal anti-inflammatory drug Suxibuzone
      (Danilon(r)). Furthermore, one established veterinary active pharmaceutical
      ingredient is applicable to additional species: The anticoccidial Amprolium
      (Eimeryl(r)) has again been authorized for chicken and turkeys. Additionally, two
      veterinary drugs with a new formulation as well as three products with a new
      strength and one product with a new indication have recently been released to the
      veterinary drugs market for horses and food producing animals. 

PMID- 23959621
TI  - Abnormal multiple pregnancy with septuplets in a cow. A case report.
AB  - A 5-year-old Brown Swiss cow being 8 months pregnant became recumbent and died.
      Postmortem examination revealed a multiple pregnancy with six normally developed
      fetuses and an amorphous globosus. The cow's internal organs were displaced and
      compressed the lungs. Fatty liver caused by metabolic disturbances was diagnosed.
      A multiple pregnancy with more than two fetuses is very rare in cattle. It could
      be induced by treatment with exogenous hormones, but it could also be the result
      of genetic selection. 

PMID- 23959622
TI  - [Nutritional laminitis--preventive measures for the obese horse].
AB  - Nutrition-induced laminitis is often caused by i) fermentation of large amounts
      of carbohydrates in the hindgut (usually fructans from grass or starch from
      cereals), which cause the release and absorption of microbial toxins and ii)
      insulin resistance induced by being overweight (equine metabolic syndrome). Both
      causes can act together. Overweight horses with a history of laminitis need to
      reduce body weight to prevent further incidences of laminitis. Weight reduction
      occurs normally on a diet of late-cut hay, a hay-straw mixture (maximally one
      third straw to prevent constipation) or grass seed straw all at 1-1.2% of ideal
      body weight. However, this roughage allowance does not satisfy the need of horses
      to chew, for which it requires at least 1.5% of ideal body weight. This may lead
      to behavioural issues, such as allophagia and aggression, and in extreme cases,
      stereotypic behaviour. Starch concentrates should not be replaced with high fat
      concentrates. Used saw dust is recommended for bedding. The intake of grass from
      a pasture has to be considerably and efficiently reduced. If the horse is
      extremely prone to laminitis or if stable management is unreliable, abstention
      from grazing is recommended. Any supplements need to be low in energy, and should
      supply minerals and vitamins which are deficient in the diet. Some additional
      protein or amino acids may be beneficial. Regular exercise, such as a daily 30
      minute speedy trot, improves insulin sensitivity. Exercise increases energy
      expenditure to a certain extent, allowing a slight increase in the roughage
      supply, thus alleviating the conflict between energy reduction and fulfilling the
      need to chew. Weight loss should be 0.5-1% of body weight per week, while at a
      higher rate there is a potential risk of hyperlipemia. The effectiveness of the
      reducing diet should be monitored regularly, either by weighing or measuring
      body, neck or girth circumference (aiming for a reduction of 1-2 cm per week). 

PMID- 23959623
TI  - Transparency interrupted: the curtailment of the European Medicines Agency's
      Policy on access to documents.

PMID- 23959628
TI  - Charles H. DePuy (1927-2013).

PMID- 23959625
TI  - Three-dimensional mean-shift edge bundling for the visualization of functional
      connectivity in the brain.
AB  - Functional connectivity, a flourishing new area of research in human
      neuroscience, carries a substantial challenge for visualization: while the end
      points of connectivity are known, the precise path between them is not. Although
      a large body of work already exists on the visualization of anatomical
      connectivity, the functional counterpart lacks similar development. To optimize
      the clarity of whole-brain and complex connectivity patterns in three-dimensional
      brain space, we develop mean-shift edge bundling, which reveals the multitude of
      connections as derived from correlations in the brain activity of cortical
      regions.

PMID- 23959630
TI  - Bone histomorphometry of transiliac paired bone biopsies after 6 or 12 months of
      treatment with oral strontium ranelate in 387 osteoporotic women: randomized
      comparison to alendronate.
AB  - Preclinical studies indicate that strontium ranelate (SrRan) induces opposite
      effects on bone osteoblasts and osteoclasts, suggesting that SrRan may have a
      dual action on both formation and resorption. By contrast, alendronate (ALN) is a
      potent antiresorptive agent. In this multicenter, international, double-blind,
      controlled study conducted in 387 postmenopausal women with osteoporosis,
      transiliac bone biopsies were performed at baseline and after 6 or 12 months of
      treatment with either SrRan 2 g per day (n = 256) or alendronate 70 mg per week
      (n = 131). No deleterious effect on mineralization of SrRan or ALN was observed.
      In the intention-to-treat (ITT) population (268 patients with paired biopsy
      specimens), changes in static and dynamic bone formation parameters were always
      significantly higher with ALN compared with SrRan at month 6 (M6) and month 12
      (M12). Static parameters of formation were maintained between baseline and the
      last value with SrRan, except for osteoblast surfaces, which decreased at M6.
      Significant decreases in the dynamic parameters of formation (mineralizing
      surface, bone formation rate, adjusted apposition rate, activation frequency)
      were noted at M6 and M12 in SrRan. Compared with ALN, the bone formation
      parameters at M6 and M12 were always significantly higher (p < 0.001) with SrRan.
      ALN, but not SrRan, decreased resorption parameters. Compared with the baseline
      paired biopsy specimens, wall thickness was significantly decreased at M6 but not
      at M12 and cancellous bone structure parameters (trabecular bone volume,
      trabecular thickness, trabecular number, number of nodes/tissue volume) were
      significantly decreased at M12 with SrRan; none of these changes were
      significantly different from ALN. In conclusion, this large controlled paired
      biopsy study over 1 year shows that the bone formation remains higher with a
      lower diminution of the bone remodeling with SrRan versus ALN. From these
      results, SrRan did not show a significant anabolic action on bone remodeling.

PMID- 23959629
TI  - Reaction of small heat-shock proteins to different kinds of cellular stress in
      cultured rat hippocampal neurons.
AB  - Upregulation of small heat-shock proteins (sHsps) in response to cellular stress
      is one mechanism to increase cell viability.We previously described that cultured
      rat hippocampal neurons express five of the 11 family members but only upregulate
      two of them (HspB1 and HspB5) at the protein level after heat stress. Since
      neurons have to cope with many other pathological conditions, we investigated in
      this study the expression of all five expressed sHsps on mRNA and protein level
      after sublethal sodium arsenite and oxidative and hyperosmotic stress. Under all
      three conditions, HspB1, HspB5, HspB6, and HspB8 but not HspB11 were consistently
      upregulated but showed differences in the time course of upregulation. The
      increase of sHsps always occurred earlier on mRNA level compared with protein
      levels. We conclude from our data that these four upregulated sHsps (HspB1,
      HspB5, HspB6, HspB8) act together in different proportions in the protection of
      neurons from various stress conditions.

PMID- 23959631
TI  - Microscale polymer bottles corked with a phase-change material for temperature
      controlled release.
AB  - Keep your wine chilled! Microscale polystyrene (PS) bottles are loaded with dye
      molecules and then corked with a phase-change material (PCM). When the
      temperature is raised beyond its melting point, the PCM quickly melts and
      triggers an instant release of the encapsulated dye. The release profiles can be
      manipulated by using a binary mixture of PCMs with different melting points. 

PMID- 23959633
TI  - Coalescent-based method for learning parameters of admixture events from large
      scale genetic variation data.
AB  - Detecting and quantifying the timing and the genetic contributions of parental
      populations to a hybrid population is an important but challenging problem in
      reconstructing evolutionary histories from genetic variation data. With the
      advent of high throughput genotyping technologies, new methods suitable for large
      scale data are especially needed. Furthermore, existing methods typically assume
      the assignment of individuals into subpopulations is known, when that itself is a
      difficult problem often unresolved for real data. Here, we propose a novel method
      that combines prior work for inferring non reticulate population structures with
      an MCMC scheme for sampling over admixture scenarios to both identify population
      assignments and learn divergence times and admixture proportions for those
      populations using genome-scale admixed genetic variation data. We validated our
      method using coalescent simulations and a collection of real bovine and human
      variation data. On simulated sequences, our methods show better accuracy and
      faster run time than leading competitive methods in estimating admixture
      fractions and divergence times. Analysis on the real data further shows our
      methods to be effective at matching our best current knowledge about the relevant
      populations.

PMID- 23959637
TI  - Three-dimensional print of a liver for preoperative planning in living donor
      liver transplantation.
AB  - The growing demand for liver transplantation and the concomitant scarcity of
      cadaveric livers have increased the need for living donor liver transplantation
      (LDLT). Ensuring the safety of donors and recipients is critical. The
      preoperative identification of the vascular and biliary tract anatomy with 3
      dimensional (3D) printing may allow better preoperative surgical planning, avert
      unnecessary surgery in patients with potentially unsuitable anatomy, and thereby
      decrease the complications of liver transplant surgery. We developed a protocol
      and successfully 3D-printed synthetic livers (along with their complex networks
      of vascular and biliary structures) replicating the native livers of 6 patients:
      3 living donors and 3 respective recipients who underwent LDLT. To our knowledge,
      these are the first complete 3D-printed livers. Using standardized preoperative,
      intraoperative, and postoperative assessments, we demonstrated identical
      anatomical and geometrical landmarks in the 3D-printed models and native livers.

PMID- 23959638
TI  - Design and Synthesis of a Pyridine Based Chemosensor: Highly Selective
      Fluorescent Probe For Pb2+
AB  - A pyridine based imine-linked chemosensor has been synthesized and evaluated its
      binding affinity with library of transition metal ions. It has prominent
      selectivity towards Pb2+ among other metal ions in DMF/H2O (9:1, v/v) solvent
      system. The 1:1 stoichiometric was confirmed by job's plot and has a binding
      constant (Ka) = 5.142 * 103 M-1 on fluorescence. A B3LYP/6-31G and B3LYP/LanL2DZ
      basis sets were employed for optimization of 3 and 3.Pb2+.

PMID- 23959640
TI  - Intimate partner sexual violence: a comparison of foreign- versus US-born
      physically abused Latinas.
AB  - Men's violence against women-particularly intimate partner sexual violence (IPSV)
      is associated with the transmission of HIV. Men who physically abuse their female
      intimate partners often also sexually abuse them. Latinas are one of the fastest
      growing populations in the USA and at high-risk for contracting HIV, though
      little is known about IPSV against physically abused Latinas, including whether
      there is an association between nativity of the victim and the likelihood of
      sexual violence by intimate partners. This study examined the (1) prevalence of
      recent (past 6 months) IPSV against 555 physically abused, help-seeking Latinas
      and (2) relationship of nativity to recent IPSV. This study used data collected
      in 2002-2003 from participants in one major city on the East Coast and one West
      Coast county, who were involved in the Risk Assessment Validation (RAVE) Study.
      The RAVE Study assessed the accuracy of four different methods for predicting
      risk of future intimate partner violence. IPSV was defined as an abusive male
      partner physically forcing sex (rape) or making the woman have sex without a
      condom. Recent IPSV was reported by 38 % of the sample. Among those reporting
      recent IPSV, multiple assaults were common: 30%of women were raped and 51%were
      made to have unprotected sex six or more times during the past 6 months. IPSV was
      significantly associated with nativity. Physically abused Latinas who were
      foreign born had two times greater odds of reporting recent IPSV than physically
      abused Latinas born in the USA, after controlling for other demographic
      covariates. Exploratory post hoc analyses examining all pairwise comparisons of
      IPSV against Latinas born in the USA, Mexico, Central America, South America, and
      the Caribbean also revealed some significant differences that warrant further
      study with larger samples. HIV prevention efforts aimed at reducing IPSV in this
      population are needed.

PMID- 23959641
TI  - Supramolecular polymerization in microfluidic channels: spatial control over
      multiple intermolecular interactions.
AB  - A novel supramolecular assembly has been developed in conjugation with
      microfluidics. Self-assembly of the programmed molecules was controlled
      precisely, in space and time, in a microflow channel as a result of a homogeneous
      solvent mixing process. Furthermore, through continuous organization of component
      molecules followed by orientation along microflow, the self-assembling event
      containing different molecules was spatially controlled from nano to micrometer
      scale in a single stream (GMP=guanosine 5'-monophosphate). 

PMID- 23959639
TI  - Distinct roles of Drosophila cacophony and Dmca1D Ca(2+) channels in synaptic
      homeostasis: genetic interactions with slowpoke Ca(2+) -activated BK channels in
      presynaptic excitability and postsynaptic response.
AB  - Ca(2+) influx through voltage-activated Ca(2+) channels and its feedback
      regulation by Ca(2+) -activated K(+) (BK) channels is critical in Ca(2+) 
      dependent cellular processes, including synaptic transmission, growth and
      homeostasis. Here we report differential roles of cacophony (CaV 2) and Dmca1D
      (CaV 1) Ca(2+) channels in synaptic transmission and in synaptic homeostatic
      regulations induced by slowpoke (slo) BK channel mutations. At Drosophila larval
      neuromuscular junctions (NMJs), a well-established homeostatic mechanism of
      transmitter release enhancement is triggered by experimentally suppressing
      postsynaptic receptor response. In contrast, a distinct homeostatic adjustment is
      induced by slo mutations. To compensate for the loss of BK channel control
      presynaptic Sh K(+) current is upregulated to suppress transmitter release,
      coupled with a reduction in quantal size. We demonstrate contrasting effects of
      cac and Dmca1D channels in decreasing transmitter release and muscle
      excitability, respectively, consistent with their predominant pre- vs.
      postsynaptic localization. Antibody staining indicated reduced postsynaptic
      GluRII receptor subunit density and altered ratio of GluRII A and B subunits in
      slo NMJs, leading to quantal size reduction. Such slo-triggered modifications
      were suppressed in cac;;slo larvae, correlated with a quantal size reversion to
      normal in double mutants, indicating a role of cac Ca(2+) channels in slo
      triggered homeostatic processes. In Dmca1D;slo double mutants, the quantal size
      and quantal content were not drastically different from those of slo, although
      Dmca1D suppressed the slo-induced satellite bouton overgrowth. Taken together,
      cac and Dmca1D Ca(2+) channels differentially contribute to functional and
      structural aspects of slo-induced synaptic modifications.

PMID- 23959642
TI  - Using the neanderthal and denisova genetic data to understand the common MAPT
      17q21 inversion in modern humans.
AB  - The polymorphic inversion on 17q21, that includes the MAPT gene, represents a
      unique locus in the human genome characterized by a large region with strong
      linkage disequilibrium. Two distinct haplotypes, H1 and H2, exist in modern
      humans, and H1 has been unequivocally related to several neurodegenerative
      disorders. Recent data indicate that recurrent inversions of this genomic region
      have occurred through primate evolution, with the H2 haplotype being the
      ancestral state. Neandertals harbored the H1 haplotype; however, until now, no
      data were available for the Denisova hominin. Neandertals and Denisovans are
      sister groups that share a common ancestor with modern humans. We analyzed the
      MAPT sequence and assessed the differences between modern humans, Neandertals,
      Denisovans, and great apes. Our analysis indicated that the Denisova hominin
      carried the H1 haplotype, and the Neandertal and Denisova common ancestor
      probably shared the same subhaplotype (H1j). We also found 68 intronic variants
      within the MAPT gene, 23 exclusive to Denisova hominin, 6 limited to Neandertals,
      and 24 exclusive to present-day humans. Our results reinforce previous data; this
      suggests that the 17q21 inversion arose within the modern human lineage. The data
      also indicate that archaic hominins that coexisted in Eurasia probably shared the
      same MAPT subhaplotype, and this can be found in almost 2% of chromosomes from
      European ancestry. 

PMID- 23959643
TI  - A tale of two haplotypes: the EDA2R/AR Intergenic region is the most divergent
      genomic segment between Africans and East Asians in the human genome.
AB  - Single nucleotide polymorphisms (SNPs) with large allele frequency differences
      between human populations are relatively rare. The longest run of SNPs with an
      allele frequency difference of one between the Yoruba of Nigeria and the Han
      Chinese is found on the long arm of the X chromosome in the intergenic region
      separating the EDA2R and AR genes. It has been proposed that the unusual allele
      frequency distributions of these SNPs are the result of a selective sweep
      affecting African populations that occurred after the out-of-Africa migration. To
      investigate the evolutionary history of the EDA2R/AR intergenic region, we
      characterized the haplotype structure of 52 of its highly differentiated SNPs.
      Using a publicly available data set of 3,000 X chromosomes from 65 human
      populations, we found that nearly all human X chromosomes carry one of two modal
      haplotypes for these 52 SNPs. The predominance of two highly divergent haplotypes
      at this locus was confirmed by use of a subset of individuals sequenced to high
      coverage. The first of these haplotypes, the alpha-haplotype is at high
      frequencies in most of the African populations surveyed and likely arose before
      the separation of African populations into distinct genetic entities. The second,
      the beta-haplotype, is frequent or fixed in all non-African populations and
      likely arose in East Africa before the out-of-Africa migration. We also observed
      a small group or rare haplotypes with no clear relationship to the alpha- and
      beta-haplotypes. These haplotypes occur at relatively high frequencies in African
      hunter-gatherer populations, such as the San and Mbuti Pygmies. Our analysis
      indicates that these haplotypes are part of a pool of diverse, ancestral
      haplotypes that have now been almost entirely replaced by the alpha- and beta
      haplotypes. We suggest that the rise of the alpha- and beta-haplotypes was the
      result of the demographic forces that human populations experienced during the
      formation of modern African populations and the out-of-Africa migration. However,
      we also present evidence that this region is the target of selection in the form
      of positive selection on the alpha- and beta-haplotypes and of purifying the
      selection against alpha/beta recombinants. 

PMID- 23959644
TI  - Extensive population structure in San, Khoe, and mixed ancestry populations from
      southern Africa revealed by 44 short 5-SNP haplotypes.
AB  - The San and Khoe people currently represent remnant groups of a much larger and
      widely distributed population of hunter-gatherers and pastoralists who had
      exclusive occupation of southern Africa before the arrival of Bantu-speaking
      groups in the past 1,200 years and sea-borne immigrants within the last 350
      years. Genetic studies [mitochondrial deoxyribonucleic acid (DNA) and Y
      chromosome] conducted on San and Khoe groups revealed that they harbor some of
      the most divergent lineages found in living peoples throughout the world.
      Recently, high-density, autosomal, single-nucleotide polymorphism (SNP)-array
      studies confirmed the early divergence of Khoe-San population groups from all
      other human populations. The present study made use of 220 autosomal SNP markers
      (in the format of both haplotypes and genotypes) to examine the population
      structure of various San and Khoe groups and their relationship to other
      neighboring groups. Whereas analyses based on the genotypic SNP data only
      supported the division of the included populations into three main groups-Khoe
      San, Bantu-speakers, and non-African populations-haplotype analyses revealed
      finer structure within Khoe-San populations. By the use of only 44 short SNP
      haplotypes (compiled from a total of 220 SNPs), most of the Khoe-San groups could
      be resolved as separate groups by applying STRUCTURE analyses. Therefore, by
      carefully selecting a few SNPs and combining them into haplotypes, we were able
      to achieve the same level of population distinction that was achieved previously
      in high-density SNP studies on the same population groups. Using haplotypes
      proved to be a very efficient and cost-effective way to study population
      structure. 

PMID- 23959645
TI  - The Effect of ACP1-ADA1 Genetic Interaction on Human Life Span.
AB  - Acid phosphatase (ACP1) is a polymorphic enzyme that catalyzes the conversion of
      flavin-mononucleotide (FMN) to riboflavin and regulates the cellular
      concentration of flavin-adenine-dinucleotide (FAD) and, consequently, energy
      metabolism. Its activity is modulated by adenosine deaminase locus 1 (ADA1)
      genotype. The aim of our work is to verify whether individuals with a high
      proportion of ACP1 f-isozyme and carrying the ADA1*2 allele, displaying the
      highest phosphatase activity, may have a higher life expectancy. Genomic DNA was
      extracted from the peripheral blood of 569 females and 509 males (18 to 106 years
      of age) randomly recruited from Central Italy. These samples were subdivided into
      three sex-specific age groups (the ages of women are in square bracket): Class 1:
      age <66 [<73]; Class 2: ages 66 to 88 [73 to 91]; Class 3: age >88 [>91]. ACP1and
      ADA1 singlenucleotide polymorphisms (SNPs) were genotyped by restriction fragment
      length polymorphism-polymerase chain reaction (RFLP-PCR) methods and statistical
      analyses were performed with SPSS 14.0. The results showed a larger proportion of
      Class 3 individuals displaying high ACP1 f-isozyme concentration and carrying the
      ADA1*2 allele than those individuals of Class 2 and Class 2 plus Class 1. Thus,
      we postulate that in Class 3 individuals the high phosphatase activity, resulting
      from the combined presence of high ACP1 f-isozyme concentration and the ADA1*2
      allele, lowers the rate of glycolysis that may reduce the amount of metabolic
      calories and, in turn, activate Sirtuin genes that protect cells against age
      related diseases. 

PMID- 23959646
TI  - Analysis of a genetic isolate: the case of Carloforte (Italy).
AB  - We reviewed data collected during several studies concerning the genetic isolate
      of Carloforte (Sardinia, Italy) and analyzed new data on Y-chromosome markers.
      Carloforte is also a language island, where people still speak Tabarchino, an
      archaic form of Ligurian dialect. Demographic data indicate that, in the early
      years of its history, the Carloforte population was characterized by a high
      degree of endogamy and consanguinity rates that started to decrease around 1850,
      when marriages with Sardinian people began to occur more frequently. Cultural
      factors, mainly language, account for the high endogamy. Genetic data from
      classical markers, mtDNA, and Y-chromosome markers confirmed the strong isolation
      of the Carloforte population, which appears significantly different from the
      neighboring population of Sardinia. Analysis of mtDNA emphasizes the crucial
      aspect of sampling strategy-two different samplings of the same population (one
      based on founder surnames; the other based on grandparents' criterion) gave
      different results. Founder surnames sampling is not affected by recent events,
      and therefore it better describes the ancestral population, whereas,
      grandparents' criterion sampling gives a picture of the present population,
      shaped by more recent events, such as migration and gene flow. This review
      further supports the notion that a comprehensive approach, including a detailed
      knowledge of the history of the population and the collection of different
      samplings, is essential in anthropology for reconstructing past and recent events
      that contributed to establishing the present genetic structure of the population.
      Likewise, it is essential in medical genetics to identify genes involved in
      complex diseases. An ideal scenario is offered by a genetic isolate with a
      recent, and well-documented, history, such as Carloforte, that can ba a paradigm
      for this type of investigation. 

PMID- 23959647
TI  - Front speed of language replacement.
AB  - We use two coupled equations to analyze the space/time dynamics of two
      interacting languages. First, we introduce a cohabitation model, which is more
      appropriate for human populations than classical (noncohabitation) models.
      Second, using numerical simulations, we find the front speed of a new language
      spreading into a region in which another language was previously used. Third, for
      a special case, we derive an analytical formula that makes it possible to check
      the validity of our numerical simulations. Finally, as an example, we find that
      the observed front speed for the spread of the English language into Wales in the
      period 1961 through 1981 is consistent with the model predictions. We also find
      that the effects of linguistic parameters are much more important than the
      effects of parameters related to population dispersal and reproduction. If the
      initial population densities of both languages are similar, they have no effect
      on the front speed. We outline the potential of the new model to analyze
      relationships between language replacement and genetic replacement. 

PMID- 23959650
TI  - In vivo differential susceptibility of sensory neurons to rabies virus infection.
AB  - There is controversy with regard to the entry pathway of the rabies virus (RABV)
      into the central nervous system (CNS). Some authors have suggested that the virus
      inoculated at the periphery is captured and transported to CNS only by motor
      neurons; however, it has been reported that dorsal root ganglia (DRG) sensory
      neurons capture and transport the virus to the spinal cord (SC) and then to the
      brain. It is probable that preferences for one pathway or another depend on the
      site of inoculation and the post-infection time. Therefore, in the present study,
      we evaluated different vertebral segments and post-infection times, along with
      the location, number, and subpopulation of sensory neurons susceptible to
      infection after inoculating RABV in the footpads of adult mice. It was noted that
      the virus inoculated in the footpad preferentially entered the CNS through the
      large-sized DRG sensory neurons, while infection of the motor neurons occurred
      later. Further, it was found that the virus was dispersed in spinal cord trans
      synaptically through the interneurons, arriving at both sensory neurons and
      contralateral motor neurons. In conclusion, we observed that RABV inoculated in
      the plantar footpad is captured preferentially by large sensory neurons and is
      transported to the DRG, where it replicates and is spread to the SC using
      transynaptic jumps, infecting sensory and motor neurons at the same level before
      ascending to the brain.

PMID- 23959651
TI  - Indoor tanning among young non-Hispanic white females.

PMID- 23959649
TI  - Ten years of progress in the Hokkaido birth cohort study on environment and
      children's health: cohort profile--updated 2013.
AB  - The Hokkaido Study on Environment and Children's Health is an ongoing cohort
      study that began in 2002. The study consists of two prospective birth cohorts,
      the Sapporo cohort (n = 514) and the Hokkaido large-scale cohort (n = 20,940).
      The primary goals of this study are to first examine the potential negative
      effects of perinatal environmental chemical exposures on birth outcomes,
      including congenital malformations and growth retardation; second, to evaluate
      the development of allergies, infectious diseases and neurodevelopmental
      disorders and perform longitudinal observations of the children's physical
      development to clarify the causal relationship between these outcomes and
      environmental chemicals; third, to identify individuals genetically susceptible
      to environmental chemicals; finally, to identify the additive effects of various
      environmental factors in our daily life, such as secondhand smoke exposure or low
      folate intake during early pregnancy. In this paper, we introduce our recent
      progress in the Hokkaido study with a cohort profile updated in 2013. For the
      last ten years, we followed pregnant women and their offspring, measuring various
      environmental chemicals, i.e., PCB, OH-PCB and dioxins, PFCs (Perfluorinated
      Compounds), Organochlorine pesticides, Phthalates, bisphenol A and mercury. We
      discovered that the concentration of toxic equivalents (TEQ) of dioxin and other
      specific congeners of PCDF or PCDD have effects on birth weight, infants'
      neurodevelopment and immune function. There were significant gender differences
      in these effects; our results suggest that male infants have more susceptibility
      to those chemical exposures than female infants. Interestingly, we found maternal
      genetic polymorphisms in AHR, CYP1A1 or GSTs that significantly modified the
      dioxin concentrations in maternal blood, suggesting different dioxin
      accumulations in the bodies of individuals with these genotypes, which would lead
      to different dioxin exposure levels. These genetic susceptibility factors
      influenced the body size of children born from mothers that either smoked or were
      passively exposed to tobacco smoke. Further studies investigating the correlation
      between epigenetics, the effects of intrauterine exposure to environmental
      chemicals and developmental factors related to health and disease are warranted.

PMID- 23959652
TI  - Moving past "One size (and number) fits all" in the selection of candidates with
      hepatocellular carcinoma for liver transplantation.

PMID- 23959653
TI  - Sc65 is a novel endoplasmic reticulum protein that regulates bone mass
      homeostasis.
AB  - Members of the Leprecan family of proteins include enzymes, prolyl 3-hydroxylase
      1 (P3h1), P3h2, and P3h3, and nonenzymatic proteins, Crtap and Sc65. Mutations in
      CRTAP and LEPRE1 (encoding P3H1) have been associated with human disease such as
      recessive osteogenesis imperfecta; however, the function of Sc65, which is
      closely related and highly homologous to Crtap, is unknown. Sc65 has been
      described as a synaptonemal complex protein, a nucleolar protein, and a
      cytoplasmic adapter protein. In light of its high sequence similarity with Crtap,
      an endoplasmic reticulum (ER)-associated protein, and the importance of post
      translational modifications such as collagen prolyl 3-hydroxylation in bone
      metabolism, we hypothesized that Sc65 was an ER-resident protein that would have
      an important role in bone homeostasis. In this study, we demonstrate that Sc65 is
      a previously unrecognized ER protein and that it does not localize in the nucleus
      of somatic cells. Moreover, Sc65 is expressed and functional during skeletal
      development because loss of Sc65 results in a progressive osteopenia that affects
      both trabecular and cortical bone. Bone loss is the result of increased bone
      resorption mediated by a non-cell-autonomous effect on osteoclasts. Therefore,
      Sc65, like its related family member Crtap, is an important modulator of bone
      homeostasis, acting as a negative regulator of osteoclastogenesis.

PMID- 23959654
TI  - Synthesis, pharmacophores, and mechanism study of pyridin-2(1H)-one derivatives
      as regulators of translation initiation factor 3A.
AB  - Twenty-seven 1,5-disubstituted-pyridin-2(1H)-one derivatives were synthesized and
      evaluated for their anti-cancer and anti-fibrosis activity by A549 and NIH3T3
      cell viability assays, respectively. To study the selectivity between the cancer
      and fibrosis cell lines, pharmacophore models (F1-F4) were built in advance for
      compounds with pyridin-2(1H)-one scaffold, which revealed the relationship
      between the occupation of the aromatic sub-site F4 and potent anti-cancer
      activity. The relationship between structure and anti-cancer activity for all
      target compounds is also reported herein: 1-Phenyl-5-((m
      tolylamino)methyl)pyridine-2(1H)-one (22) displayed both potency and selectivity
      (IC50=0.13 mM) toward the A549 cell line through the inhibition of translation
      initiation, especially by eIF3a suppression, and can be treated as a lead for the
      design of novel eIF3a regulators and anti-lung cancer agents.

PMID- 23959655
TI  - Energy drink consumption and associated health behaviors among university
      students in an urban setting.
AB  - The objective of this study is to describe energy drink consumption and health
      behaviors among college students attending a predominantly minority university.
      Undergraduate and graduate students attending a private, minority-serving
      university were invited to participate in an online survey between September 2009
      and August 2010. Out of 2,500 students, 407 participated yielding a response of
      16 %. Analysis assessed energy drink consumption as well as participation in
      sport activities and high-risk behaviors. Energy drink consumption is
      significantly related with drinking alcohol to inebriation and driving (r = .14,
      p < .05) and to riding with a drunk driver (r = .15, p < .05). Athletes were more
      likely to engage in drinking alcohol to inebriation and driving F (1, 186) =
      6.12, p < .02. Energy drink consumption is a common practice among racial
      minority university students. Tailored health promotion strategies and
      interventions are needed to address misconceptions of energy drink and alcohol
      mixing.

PMID- 23959656
TI  - New insights into mRNA trafficking in axons.
AB  - In recent years, it has been demonstrated that mRNAs localize to axons of young
      and mature central and peripheral nervous system neurons in culture and in vivo.
      Increasing evidence is supporting a fundamental role for the local translation of
      these mRNAs in neuronal function by regulating axon growth, maintenance and
      regeneration after injury. Although most mRNAs found in axons are abundant
      transcripts and not restricted to the axonal compartment, they are sequestered
      into transport ribonucleoprotein particles and their axonal localization is
      likely the result of specific targeting rather than passive diffusion. It has
      been reported that long-distance mRNA transport requires microtubule-dependent
      motors, but the molecular mechanisms underlying the sorting and trafficking of
      mRNAs into axons have remained elusive. This review places particular emphasis on
      motor-dependent transport of mRNAs and presents a mathematical model that
      describes how microtubule-dependent motors can achieve targeted trafficking in
      axons. A future challenge will be to systematically explore how the numerous
      axonal mRNAs and RNA-binding proteins regulate different aspects of specific
      axonal mRNA trafficking during development and after regeneration.

PMID- 23959657
TI  - Salts of C60(OH)8 electrodeposited onto a glassy carbon electrode: surprising
      catalytic performance in the hydrogen evolution reaction.

PMID- 23959658
TI  - Permanent neonatal diabetes mellitus in monozygotic twins achieving low-dose
      sulfonylurea therapy.
AB  - Although KCNJ11 mutations of the KATP channel within the beta cell are known to
      prevent insulin secretion and cause permanent neonatal diabetes mellitus, the
      genotype-phenotype correlation continues to be of clinical interest. We report
      the clinical outcomes in monozygotic twins with neonatal diabetes due to
      heterozygous mutations in KCNJ11 at R201H. The twins demonstrated concordant
      clinical outcomes after transitioning from insulin to oral sulfonylurea therapy
      at 4 months of age. Both twins remained on sulfonylurea therapy while achieving
      similar growth, development, and metabolic goals. They exhibit marked sensitivity
      to sulfonylurea therapy with current dosing at 0.05 and 0.06 mg/kg per day at age
      5 years which deviates from the approximate maintenance dose of 0.4 mg/kg per day
      at the time of transition and subsequent follow-up. Metabolic control provided by
      low-dose sulfonylurea therapy is likely due to early age at transition from
      insulin to sulfonylurea therapy and possible preservation of endogenous insulin
      secretion.

PMID- 23959659
TI  - Age of thelarche and menarche in contemporary US females: a cross-sectional
      analysis.
AB  - AIM: A recent secular trend towards earlier thelarche has been suggested. The aim
      of this study is to examine normative ages of thelarche and menarche in
      contemporary US females. METHODS: Trained physicians documented Tanner breast
      stage by observation in a cross-sectional cohort. Age of menarche was self
      reported. The subjects were healthy female children and adolescents. The mean age
      of thelarche was determined by probit analysis and the mean age of menarche was
      determined by using a normal time-to-event model. RESULTS: Mean age of thelarche
      was 9.7 years among 610 females aged 3.0-17.9 years (70% non-Hispanic Caucasian
      (NHC), 14% African-Americans, 7% Hispanic, 9% "other"). The mean age of menarche
      was 12.8 years for NHC, with African-Americans having menarche 0.6 years earlier.
      CONCLUSIONS: Thelarche occurred earlier than recently reported, while age of
      menarche remained unchanged, this supported a persistent secular trend towards
      earlier thelarche but stable age of menarche. This suggests that the observed
      thelarche is gonadotropin-independent or the tempo of pubertal advancement has
      slowed.

PMID- 23959660
TI  - Skeletal maturation and predicted adult height in children with premature
      adrenarche.
AB  - OBJECTIVE: Premature adrenarche (PA) may be associated with obesity and advanced
      bone age. Our objective was to determine if children with PA had a predicted
      adult height less than target height. METHODS: A retrospective chart review
      identified 100 children originating predominantly from South and Central America
      and the Caribbean region previously diagnosed with PA from one pediatric
      endocrinology clinic. RESULTS: The majority (89.2%) of the sample had advanced
      bone age, while 43.4% were obese and 41.8% had a predicted height below target.
      There was a significant correlation between body mass index Z-score and bone age
      advancement among boys (r=0.67, p<0.001). The majority (72.7%) of those with a
      predicted height below target had a bone age advancement of two standard
      deviations or more. CONCLUSIONS: These findings suggest that PA and obesity are
      associated with rapid skeletal maturation and that significant bone age
      advancement in PA is associated with a sub-optimal adult height.

PMID- 23959661
TI  - Israel Society for Auditory Research (ISAR): 2013 Annual Scientific Conference.

PMID- 23959662
TI  - The relationship between oxidative stress and exercise.
AB  - Physical exercise has many benefits, but it might also have a negative impact on
      the body, depending on the training level, length of workout, gender, age and
      fitness. The negative effects of physical exercise are commonly attributed to an
      imbalance between the levels of antioxidants (both low molecular weight
      antioxidants and antioxidant enzymes) and reactive oxygen and nitrogen species
      due to excessive production of free radicals during physical exercise. In this
      critical review, we look for answers for three specific questions regarding the
      interrelationship between physical exercise and oxidative stress (OS), namely,
      (i) the dependence of the steady-state level of OS on fitness, (ii) the effect of
      intensive exercise on the OS and (iii) the dependence of the effect of the
      intense exercise on the individual fitness. All these questions have been raised,
      investigated and answered, but the answers given on the basis of different
      studies are different. In the present review, we try to explain the reason(s) for
      the inconsistencies between the conclusions of different investigations, commonly
      based on the concentrations of specific biomarkers in body fluids. We think that
      most of the inconsistencies can be attributed to the difference between the
      criteria of the ill-defined term denoted OS, the methods used to test them and in
      some cases, between the qualities of the applied assays. On the basis of our
      interpretation of the differences between different criteria of OS, we consider
      possible answers to three well-defined questions. Possible partial answers are
      given, all of which lend strong support to the conclusion that the network
      responsible for homeostasis of the redox status is very effective. However, much
      more data are required to address the association between exercise and OS and its
      dependence on various relevant factors.

PMID- 23959663
TI  - Differential contributions of the latch in Thermotoga maritima reverse gyrase to
      the binding of single-stranded DNA before and after ATP hydrolysis.
AB  - Reverse gyrase catalyzes the ATP-dependent introduction of positive supercoils
      into DNA. Supercoiling requires the functional cooperation of its N-terminal
      helicase domain with the C-terminal topoisomerase domain. The helicase domain
      contains a superfamily 2 helicase core formed by two RecA domains, H1 and H2. We
      show here that a helicase domain lacking the latch, an insertion in H2, fails to
      close the cleft in the helicase core in response to nucleotide and DNA binding at
      the beginning of the catalytic cycle. In the presence of the pre-hydrolysis ATP
      analog ADP.BeFx, however, the closed conformer can still be formed in the absence
      of the latch. The helicase domain lacking the latch exhibits reduced DNA
      affinities. The energetic difference between the two nucleotide states involved
      in duplex separation is diminished, rationalizing the unwinding deficiency of
      reverse gyrase lacking the latch. The latch most strongly contributes to binding
      of single-stranded DNA in the post-hydrolysis state, before phosphate release.
      Our results are in line with contributions of the latch in determining the
      direction of strand passage, and in orienting the cleaved single-stranded DNA for
      re-ligation. At the same time, the latch may coordinate the re-ligation reaction
      with strand passage and with the nucleotide cycle.

PMID- 23959664
TI  - Molecular triggers of neuroinflammation in mouse models of demyelinating
      diseases.
AB  - Myelinating cells wrap axons with multi-layered myelin sheaths for rapid impulse
      propagation. Dysfunctions of oligodendrocytes or Schwann cells are often
      associated with neuroinflammation, as observed in animal models of
      leukodystrophies and peripheral neuropathies, respectively. The neuroinflammatory
      response modulates the pathological changes, including demyelination and axonal
      injury, but also remyelination and repair. Here we discuss different immune
      mechanisms as well as factors released or exposed by myelinating glia in disease
      conditions. The spectrum of inflammatory mediators varies with different myelin
      disorders and has a major impact on the beneficial or detrimental role of immune
      cells in keeping nervous system integrity.

PMID- 23959665
TI  - PBMC expressed adiponectin mRNA is predictive of survival in patients with
      gastric cancer.

PMID- 23959666
TI  - Do we really need high-sensitive troponin immunoassays in the emergency
      department? Definitely, yes!
AB  - Cardiac troponins have changed our understanding of myocardial infarction
      profoundly during the past 20 years. In fact release of cardiac troponin into the
      blood has become part of the definition of myocardial infarction. Diagnostics and
      treatment have taken these new insights into account. The novel high-sensitive
      assays for cardiac troponins that are available recently clearly constitute a
      significant further improvement of analytical performance. In addition, the still
      incomplete clinical data available indicate that these assays will also further
      improve patient care in many ways. In summary, cardiac troponins are a great
      example of the potential impact of analytical performance of diagnostic tests on
      patient care and patient outcome.

PMID- 23959667
TI  - Syncope in children and adolescents living in north-eastern Poland - scope of
      causes.
AB  - PURPOSE: To investigate the diagnostic yield of different tests and asses the
      scope of causes in children referring to the hospital with a syncope in north
      eastern Poland. METHODS: A review of 386 consecutive patients (age 2-18 years)
      living in north-eastern Poland presenting to the cardiology department with a new
      onset syncope (which appeared to be neurally mediated by history) was undertaken.
      The patients underwent physical examination, laboratory tests,
      electrocardiography, 24-holter monitoring, head-up tilt-test, exercise test,
      echocardiography and electroencephalography. All the tests were performed in most
      of the patients, without ending the diagnostics after finding the first probable
      cause of loss of consciousness. RESULTS: 229 potential causes of syncope were
      found in 191 patients (49.4%), with 2 possible causes in 32 patients and 3
      potential causes in 3 patients. The top 3 tests with the highest diagnostic yield
      were: head-up tilt test (41.4%), 24-holter monitoring (14.5%) and
      echocardiography (8.4%). Electroencephalography was useful in 3 patients (1.5%)
      and exercise test did not help in any patient. CONCLUSION: In some children more
      than one potential cause of syncope was diagnosed. That might confirm multiple
      factors' causality of syncope. Head-up tilt-test has the highest diagnostic yield
      in children with syncope. If the diagnostic protocol is not very strict, one
      might find some crucial conditions in about 8.3% of patients.

PMID- 23959668
TI  - Age and gender predict OPG level and OPG/sRANKL ratio in maintenance hemodialysis
      patients.
AB  - PURPOSE: Cardiovascular disease (CVD) is a major cause of death among chronic
      hemodialysis (HD) patients. Gender and age belong to its classical risk factors.
      OPG/RANK/sRANKL (Osteoprotegerin/ Receptor Activator of Nuclear Factor kappaB/
      soluble Receptor Activator of Nuclear Factor kappaB Ligand) axis constitute a
      system connecting bone and vascular remodeling. METHODS: We aimed to evaluate the
      plasma levels of OPG, sRANKL and OPG/sRANKL ratio in 21 HD patients and 16
      healthy volunteers in relation to gender, age and the other clinical parameters.
      RESULTS: OPG and OPG/sRANKL ratio were significantly higher in HD patients than
      in controls whereas sRANKL was similar in both groups. Adjusted for gender, in
      controls OPG were higher in women whereas sRANKL did not differ between men and
      women. In HD group OPG and sRANKL were higher in women whereas OPG/sRANKL ratio
      was similar in both genders. Female patients compared to healthy women revealed
      56% higher OPG concentration and 54% higher OPG/ sRANKL ratio. Comparison of male
      patients and controls revealed 61% higher level of OPG and 75% higher OPG/sRANKL
      ratio in HD group. Interestingly, OPG and OPG/sRANKL ratio positively correlated
      with age only in male patients. Contrary, the association between OPG/sRANKL
      ratio and age was negative in HD women. CONCLUSION: Higher OPG levels in HD women
      comparing to age matched HD men indicate the necessity of more careful screening
      towards the presence of CVD and bone-mineral disorders. The negative association
      between age and OPG/ sRANKL ratio in HD women warrant in-depth study for thorough
      understanding of this complex interrelationship.

PMID- 23959669
TI  - Over-dialysis plasma RANTES increase depends on heparin dose and cardiovascular
      disease status.
AB  - PURPOSE: The lifespan of maintenance hemodialysis patients is reduced mainly
      because of cardiovascular complications due to accelerated atherosclerosis and
      impaired angiogenesis. We aimed to compare the effect of unfractionated heparin
      (UFH) and enoxaparin used as anticoagulants during hemodialysis (HD) on
      circulating levels of heparin-binding, anti-angiogenic Endostatin, pro
      inflammatory RANTES (Regulated upon Activation, Normal T cell Expressed and
      Secreted), and MCP-1 (Monocyte Chemoattractant Protein-1). METHODS: We enrolled
      22 chronic HD patients, who were randomly assigned to either enoxaparin (n=11) or
      UFH (n=11) anticoagulation, and followed prospectively for 12 weeks before
      crossing over to the alternate therapy for further 12 weeks. The factors were
      measured (ELISA) at the start, 10 and 180 min of HD, and compared to 20 healthy
      volunteers. RESULTS: The baseline Endostatin, RANTES, and MCP-1 levels in
      patients were higher than in controls and comparable during enoxaparin and UFH
      treatment. RANTES significantly increased during both enoxaparin and UFH
      anticoagulated HD, while over-HD Endostatin and MCP-1 levels remained stable
      regardless of the heparin sort. About 25% RANTES increase after 10 min of HD
      positively correlated with the dose of both heparins and HD duration. The switch
      from enoxaparin to UFH treatment had no impact on the levels of parameters
      studied. Patients with ischemic heart disease had less RANTES increase after 180
      min of HD especially during enoxaparin treatment. CONCLUSION: RANTES is dose
      depended and transitory increased in response to both UFH and enoxaparin
      administration during HD. Cardiovascular disease status occurred to be the most
      important predictor of its over-HD level.

PMID- 23959670
TI  - Optimal setting of image bounding box can improve registration accuracy of
      diffusion tensor tractography.
AB  - PURPOSE: When we register diffusion tensor tractography (DTT) to anatomical
      images such as fast imaging employing steady-state acquisition (FIESTA), we
      register the B0 image to FIESTA. Precise registration of the DTT B0 image to
      FIESTA is possible with non-rigid registration compared to rigid registration,
      although the non-rigid methods lack convenience. We report the effect of image
      data bounding box settings on registration accuracy using a normalized mutual
      information (NMI) method METHODS: MRI scans of 10 patients were used in this
      study. Registration was performed without modification of the bounding box in the
      control group, and the results were compared with groups re-registered using
      multiple bounding boxes limited to the region of interest (ROI). The distance of
      misalignment after registration at 3 anatomical characteristic points that are
      common to both FIESTA and B0 images was used as an index of accuracy. RESULTS:
      Mean ([Formula: see text]SD) misalignment at the 3 anatomical points decreased
      significantly from [Formula: see text] to [Formula: see text] mm, [Formula: see
      text]), [Formula: see text] to [Formula: see text] mm, ([Formula: see text], and
      [Formula: see text] to [Formula: see text] mm, ([Formula: see text], each showing
      improvement compared to the control group CONCLUSION: Narrowing the image data
      bounding box to the ROI improves the accuracy of registering B0 images to FIESTA
      by NMI method. With our proposed methodology, accuracy can be improved in
      extremely easy steps, and this methodology may prove useful for DTT registration
      to anatomical image.

PMID- 23959671
TI  - An automated insertion tool for cochlear implants with integrated force sensing
      capability.
AB  - PURPOSE: Minimally invasive cochlear implantation and residual hearing
      preservation require both the surgical approach to the cochlea as well as the
      implant insertion to be performed in an atraumatic fashion. Considering the
      geometric limitations of this approach, specialized instrumentation is required
      to insert the electrode while preserving intracochlear membranes carrying the
      sensory hair cells. METHODS: An automated insertion tool for cochlear implants,
      which is capable of sensing insertion forces with a theoretical resolution of 30
      MUN, is presented. In contrast to previous designs, the custom force sensor is
      integrated in the insertion mechanism. Moreover, a test bench for insertion
      studies under constant and reproducible boundary conditions is proposed. It is
      used to experimentally validate the force sensing insertion tool, which is
      achieved by comparing the acquired forces to a ground truth measurement. The
      results of insertion studies on both an acrylic cochlear phantom and temporal
      bone specimen are given and discussed. RESULTS: Results reveal that friction,
      occurring between the electrode carrier and the inside of the insertion tool
      guide tube, is likely to affect the force output of the proposed sensor. An
      appropriate method to compensate for these disturbances is presented and
      experimentally validated. Using the proposed approach to friction identification,
      a mean accuracy of (4.0+/-3.2) mN is observed. CONCLUSIONS: The force information
      provided by the proposed, automated insertion tool can be used to detect
      complications during electrode insertion. However, in order to obtain accurate
      results, an identification of frictional forces prior to insertion is mandatory.
      The insertion tool is capable of automatically executing the appropriate
      trajectories.

PMID- 23959672
TI  - Transcriptional and functional regulation of the intestinal peptide transporter
      PEPT1.
AB  - Dietary proteins are cleaved within the intestinal lumen to oligopeptides which
      are further processed to small peptides (di- and tripeptides) and free amino
      acids. Although the transport of amino acids is mediated by several specific
      amino acid transporters, the proton-coupled uptake of the more than 8000
      different di- and tripeptides is performed by the high-capacity/low-affinity
      peptide transporter isoform PEPT1 (SLC15A1). Its wide substrate tolerance also
      allows the transport of a repertoire of structurally closely related compounds
      and drugs, which explains their high oral bioavailability and brings PEPT1 into
      focus for medical and pharmaceutical approaches. Although the first evidence for
      the interplay of nutrient supply and PEPT1 expression and function was described
      over 20 years ago, many aspects of the molecular processes controlling its
      transcription and translation and modifying its transporter properties are still
      awaiting discovery. The present review summarizes the recent knowledge on the
      factors modulating PEPT1 expression and function in Caenorhabditis elegans, Danio
      rerio, Mus musculus and Homo sapiens, with focus on dietary ingredients,
      transcription factors and functional modulators, such as the sodium-proton
      exchanger NHE3 and selected scaffold proteins. 

PMID- 23959673
TI  - Exchange protein activated by cAMP (Epac) induces vascular relaxation by
      activating Ca2+-sensitive K+ channels in rat mesenteric artery.
AB  - Vasodilator-induced elevation of intracellular cyclic AMP (cAMP) is a central
      mechanism governing arterial relaxation but is incompletely understood due to the
      diversity of cAMP effectors. Here we investigate the role of the novel cAMP
      effector exchange protein directly activated by cAMP (Epac) in mediating
      vasorelaxation in rat mesenteric arteries. In myography experiments, the Epac
      selective cAMP analogue 8-pCPT-2-O-Me-cAMP-AM (5 MUM, subsequently referred to as
      8-pCPT-AM) elicited a 77.6 +/- 7.1% relaxation of phenylephrine-contracted
      arteries over a 5 min period (mean +/- SEM; n = 6). 8-pCPT-AM induced only a 16.7
      +/- 2.4% relaxation in arteries pre-contracted with high extracellular K(+) over
      the same time period (n = 10), suggesting that some of Epac's relaxant effect
      relies upon vascular cell hyperpolarization. This involves Ca(2+)-sensitive,
      large-conductance K(+) (BK(Ca)) channel opening as iberiotoxin (100 nM)
      significantly reduced the ability of 8-pCPT-AM to reverse phenylephrine-induced
      contraction (arteries relaxed by only 35.0 +/- 8.5% over a 5 min exposure to 8
      pCPT-AM, n = 5; P < 0.05). 8-pCPT-AM increased Ca(2+) spark frequency in Fluo-4
      AM-loaded mesenteric myocytes from 0.045 +/- 0.008 to 0.103 +/- 0.022 sparks s(
      1) MUm(-1) (P < 0.05) and reversibly increased both the frequency (0.94 +/- 0.25
      to 2.30 +/- 0.72 s(-1)) and amplitude (23.9 +/- 3.3 to 35.8 +/- 7.7 pA) of
      spontaneous transient outward currents (STOCs) recorded in isolated mesenteric
      myocytes (n = 7; P < 0.05). 8-pCPT-AM-activated STOCs were sensitive to
      iberiotoxin (100 nM) and to ryanodine (30 MUM). Current clamp recordings of
      isolated myocytes showed a 7.9 +/- 1.0 mV (n = 10) hyperpolarization in response
      to 8-pCPT-AM that was sensitive to iberiotoxin (n = 5). Endothelial disruption
      suppressed 8-pCPT-AM-mediated relaxation in phenylephrine-contracted arteries
      (24.8 +/- 4.9% relaxation after 5 min of exposure, n = 5; P < 0.05), as did
      apamin and TRAM-34, blockers of Ca(2+)-sensitive, small- and intermediate
      conductance K(+) (SK(Ca) and IK(Ca)) channels, respectively, and N(G)-nitro-L
      arginine methyl ester, an inhibitor of nitric oxide synthase (NOS). In Fluo-4-AM
      loaded mesenteric endothelial cells, 8-pCPT-AM induced a sustained increase in
      global Ca(2+). Our data suggest that Epac hyperpolarizes smooth muscle by (1)
      increasing localized Ca(2+) release from ryanodine receptors (Ca(2+) sparks) to
      activate BK(Ca) channels, and (2) endothelial-dependent mechanisms involving the
      activation of SK(Ca)/IK(Ca) channels and NOS. Epac-mediated smooth muscle
      hyperpolarization will limit Ca(2+) entry via voltage-sensitive Ca(2+) channels
      and represents a novel mechanism of arterial relaxation.

PMID- 23959675
TI  - The secret life of CFTR as a calcium-activated chloride channel.
AB  - cAMP-stimulated anion conductance is defective in cystic fibrosis (CF). The
      regulatory domain of CFTR, the anion channel protein encoded by the CF gene,
      possesses an unusually high density of consensus sequences for phosphorylation by
      protein kinase A (14 in a stretch of <200 amino acids). Thus it is not surprising
      that CFTR is viewed primarily as a cAMP-stimulated anion channel, and most
      studies have focused on this mode of activation. However, there is growing
      evidence that CFTR also responds to Ca(2+)-mobilizing secretagogues and
      contributes substantially to cholinergic and purinergic responses in native
      tissues. G protein-coupled receptors that signal through Galphaq can stimulate
      CFTR channels by activating Ca(2+)-dependent adenylyl cyclase and tyrosine
      kinases, and also by inhibiting protein phosphatase type 2A. Here we review
      evidence for these novel mechanisms of CFTR activation and discuss how they may
      help explain previous observations.

PMID- 23959674
TI  - Orexin neurons are indispensable for prostaglandin E2-induced fever and defence
      against environmental cooling in mice.
AB  - We recently showed using prepro-orexin knockout (ORX-KO) mice and orexin neuron
      ablated (ORX-AB) mice that orexin neurons in the hypothalamus, but not orexin
      peptides per se, are indispensable for stress-induced thermogenesis. To examine
      whether orexin neurons are more generally involved in central thermoregulatory
      mechanisms, we applied other forms of thermogenic perturbations, including brain
      prostaglandin E2 (PGE2) injections which mimic inflammatory fever and
      environmental cold exposure, to ORX-KO mice, ORX-AB mice and their wild-type (WT)
      litter mates. ORX-AB mice, but not ORX-KO mice, exhibited a blunted PGE2-induced
      fever and intolerance to cold (5 degrees C) exposure, and these findings were
      similar to the results previously obtained with stress-induced thermogenesis.
      PGE2-induced shivering was also attenuated in ORX-AB mice. Both mutants responded
      similarly to environmental heating (39 degrees C). In WT and ORX-KO mice, the
      administration of PGE2 and cold exposure activated orexin neurons, as revealed by
      increased levels of expression of c-fos. Injection of retrograde tracer into the
      medullary raphe nucleus revealed direct and indirect projection from the orexin
      neurons, of which the latter seemed to be preserved in the ORX-AB mice. In
      addition, we found that glutamate receptor antagonists (D-(-)-2-amino-5
      phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione) but not orexin
      receptor antagonists (SB334867 and OX2 29) successfully inhibited PGE2-induced
      fever in WT mice. These results suggest that orexin neurons are important in
      general thermogenic processes, and their importance is not restricted to stress
      induced thermogenesis. In addition, these results indicate the possible
      involvement of glutamate in orexin neurons implicated in PGE2-induced fever.

PMID- 23959676
TI  - Osmotic water transport in aquaporins: evidence for a stochastic mechanism.
AB  - Abstract  We test a novel, stochastic model of osmotic water transport in
      aquaporins. A solute molecule present at the pore mouth can either be reflected
      or permeate the pore. We assume that only reflected solute molecules induce
      osmotic transport of water through the pore, while permeating solute molecules
      give rise to no water transport. Accordingly, the rate of water transport is
      proportional to the reflection coefficient sigma, while the solute permeability,
      P(S), is proportional to 1 - sigma. The model was tested in aquaporins
      heterologously expressed in Xenopus oocytes. A variety of aquaporin channel sizes
      and geometries were obtained with the two aquaporins AQP1 and AQP9 and mutant
      versions of these. Osmotic water transport was generated by adding 20 mM of a
      range of different-sized osmolytes to the outer solution. The osmotic water
      permeability and the reflection coefficient were measured optically at high
      resolution and compared to the solute permeability obtained from short-term
      uptake of radio-labelled solute under isotonic conditions. For each type of
      aquaporin there was a linear relationship between solute permeability and
      reflection coefficient, in accordance with the model. We found no evidence for
      coupling between water and solute fluxes in the pore. In confirmation of
      molecular dynamic simulations, we conclude that the magnitude of the osmotic
      water permeability and the reflection coefficient are determined by processes at
      the arginine selectivity filter located at the outward-facing end of the pore.

PMID- 23959677
TI  - Phosphatidylethanolamine binding protein 1 in vacular endothelial cell autophagy
      and atherosclerosis.
AB  - We previously found that phosphatidylcholine-specific phospholipase C (PC-PLC)
      was a key inducing element of atherosclerosis, and might negatively regulate
      human umbilical vein endothelial cell (HUVEC) autophagy. To further investigate
      the mechanism of PC-PLC action, we initially identified phosphatidylethanolamine
      binding protein 1 (PEBP1) as a binding partner of PC-PLC by using mass
      spectrometry (MS, MALDI-TOF/TOF). We found that PEBP1 positively regulated PC-PLC
      activity in HUVECs, and inhibition of PC-PLC by its inhibitor D609 suppressed
      PEBP1 expression dramatically. Moreover, both PC-PLC and PEBP1 negatively
      regulated HUVEC autophagy independently of mammalian target of rapamycin (mTOR).
      Furthermore, the PEBP1 level was elevated during the development of
      atherosclerosis, while D609 significantly decreased the upregulated PEBP1 level
      in apoE(-/-) mice.

PMID- 23959678
TI  - Burst generation mediated by cholinergic input in terminal nerve-gonadotrophin
      releasing hormone neurones of the goldfish.
AB  - Peptidergic neurones play a pivotal role in the neuromodulation of widespread
      areas in the nervous system. Generally, it has been accepted that the peptide
      release from these neurones is regulated by their firing activities. The terminal
      nerve (TN)-gonadotrophin releasing hormone (GnRH) neurones, which are one of the
      well-studied peptidergic neurones in vertebrate brains, are characterised by
      their spontaneous regular pacemaker activities, and GnRH has been suggested to
      modulate the sensory responsiveness of animals. Although many peptidergic
      neurones are known to exhibit burst firing activities when they release the
      peptides, TN-GnRH neurones show spontaneous burst firing activities only
      infrequently. Thus, it remains to be elucidated whether the TN-GnRH neurones show
      burst activities and, if so, how the mode switching between the regular
      pacemaking and bursting modes is regulated in these neurones. In this study, we
      found that only a single pulse electrical stimulation of the neuropil surrounding
      the TN-GnRH neurones reproducibly induces transient burst activities in TN-GnRH
      neurones. Our combined physiological and morphological data suggest that this
      phenomenon occurs following slow inhibitory postsynaptic potentials mediated by
      cholinergic terminals surrounding the TN-GnRH neurones. We also found that the
      activation of muscarinic acetylcholine receptors induces persistent opening of
      potassium channels, resulting in a long-lasting hyperpolarisation. This long
      hyperpolarisation induces sustained rebound depolarisation that has been
      suggested to be generated by a combination of persistent voltage-gated Na(+)
      channels and low-voltage-activated Ca(2+) channels. These new findings suggest a
      novel type of cholinergic regulation of burst activities in peptidergic neurones,
      which should contribute to the release of neuropeptides.

PMID- 23959679
TI  - Effects of optional structural elements, including two alternative amino termini
      and a new splicing cassette IV, on the function of the sodium-bicarbonate
      cotransporter NBCn1 (SLC4A7).
AB  - The SLC4A7 gene encodes the electroneutral sodium/HCO3 cotransporter NBCn1, which
      plays important physiological and pathophysiological roles in many cell types.
      Previous work identified six NBCn1 variants differing in the sequence of the
      extreme N terminus--MEAD in rat only, MERF in human only--as well as in the
      optional inclusion of cassettes I, II, and III. Earlier work also left open the
      question of whether optional structural elements (OSEs) affect surface abundance
      or intrinsic (per-molecule) transport activity. Here, we demonstrate for the
      first time that SLC4A7 from one species can express both MEAD- and MERF-NBCn1. We
      also identify a novel cassette IV of 20 aa, and extend by 10 the number of full
      length NBCn1 variants. The alternative N termini and four cassettes could
      theoretically produce 32 major variants. Moreover, we identify a group of cDNAs
      predicted to encode just the cytosolic N-terminal domain (Nt) of NBCn1. A
      combination of electrophysiology and biotinylation shows that the OSEs can affect
      surface abundance and intrinsic HCO3(-) transport activity of NBCn1, as expressed
      in Xenopus oocytes. Specifically, MEAD tends to increase whereas novel cassette
      IV reduces surface abundance. Cassettes II, III and novel cassette IV all appear
      to increase the intrinsic activity of NBCn1.

PMID- 23959680
TI  - Stomatin-domain protein interactions with acid-sensing ion channels modulate
      nociceptor mechanosensitivity.
AB  - Acid-sensing ion channels (ASICs) and their interaction partners of the stomatin
      family have all been implicated in sensory transduction. Single gene deletion of
      asic3, asic2, stomatin, or stoml3 all result in deficits in the
      mechanosensitivity of distinct cutaneous afferents in the mouse. Here, we
      generated asic3(-/-):stomatin(-/-), asic3(-/-):stoml3(-/-) and asic2(-/
      ):stomatin(-/-) double mutant mice to characterize the functional consequences of
      stomatin-ASIC protein interactions on sensory afferent mechanosensitivity. The
      absence of ASIC3 led to a clear increase in mechanosensitivity in rapidly
      adapting mechanoreceptors (RAMs) and a decrease in the mechanosensitivity in both
      Adelta- and C-fibre nociceptors. The increased mechanosensitivity of RAMs could
      be accounted for by a loss of adaptation which could be mimicked by local
      application of APETx2 a toxin that specifically blocks ASIC3. There is a
      substantial loss of mechanosensitivity in stoml3(-/-) mice in which ~35% of the
      myelinated fibres lack a mechanosensitive receptive field and this phenotype was
      found to be identical in asic3(-/-):stoml3(-/-) mutant mice. However, Adelta
      nociceptors showed much reduced mechanosensitivity in asic3(-/-):stoml3(-/-)
      mutant mice compared to asic3(-/)(-) controls. Interestingly, in asic2(-/
      ):stomatin(-/-) mutant mice many Adelta-nociceptors completely lost their
      mechanosensitivity which was not observed in asic2(-/-) or stomatin(-/-) mice.
      Examination of stomatin(-/-):stoml3(-/-) mutant mice indicated that a
      stomatin/STOML3 interaction is unlikely to account for the greater Adelta
      nociceptor deficits in double mutant mice. A key finding from these studies is
      that the loss of stomatin or STOML3 in asic3(-/-) or asic2(-/-) mutant mice
      markedly exacerbates deficits in the mechanosensitivity of nociceptors without
      affecting mechanoreceptor function.

PMID- 23959682
TI  - Deep red to near-infrared emitting rhenium(I) complexes: synthesis,
      characterization, electrochemistry, photophysics, and electroluminescence
      studies.
AB  - A series of triarylamine-containing tricarbonyl rhenium(I) complexes, [BrRe(CO)3
      (N^N)] (N^N=5,5'-bis(N,N-diaryl-4-[ethen-1-yl]-aniline)-2,2'-bipyridine), has
      been designed and synthesized by introducing a rhenium(I) metal center into a
      donor-pi-acceptor-pi-donor structure. All of the complexes showed an intense
      broad structureless emission band in dichloromethane at around 680-708 nm, which
      originated from an excited state of intraligand charge transfer ((3)ILCT)
      character from the triarylamine to the bipyridine moiety. Upon introduction of
      the bulky and electron-donating pentaphenylbenzene units attached to the aniline
      groups, the emission bands were found to be red shifted. The nanosecond transient
      absorption spectra of two selected complexes were studied, which were suggestive
      of the formation of an initial charge-separated state. Computational studies have
      been performed to provide further insight into the origin of the absorption and
      emission. One of the rhenium(I) complexes has been utilized in the fabrication of
      organic light-emitting diodes (OLEDs), representing the first example of the
      realization of deep red to near-infrared rhenium(I)-based OLEDs with an emission
      extending up to 800 nm.

PMID- 23959681
TI  - The role of myogenic mechanisms in human cerebrovascular regulation.
AB  - Although myogenic mechanisms have been hypothesized to play a role in
      cerebrovascular regulation, previous data from both animals and humans have not
      provided an unequivocal answer. However, cerebral autoregulation is explicitly
      non-linear and most prior work relied on simple linear approaches for assessment,
      potentially missing important changes in autoregulatory characteristics.
      Therefore, we examined cerebral blood flow responses to augmented arterial
      pressure oscillations with and without calcium channel blockade (nicardipine)
      during blood pressure fluctuations (oscillatory lower body negative pressure,
      OLBNP) across a range of frequencies in 16 healthy subjects. Autoregulation was
      characterized via a robust non-linear method (projection pursuit regression,
      PPR). Blockade resulted in significant tachycardia, a modest but significant
      elevation in mean arterial pressure, and reductions in mean cerebral blood flow
      and end-tidal CO2 during OLBNP. The reductions in flow were directly related to
      the reductions in CO2 (r = 0.57). While linear cross-spectral analysis showed
      that the relationship between pressure-flow fluctuations was preserved after
      blockade, PPR showed that blockade significantly altered the non-linearity
      between pressure and flow, particularly at the slowest fluctuations. At 0.03 Hz,
      blockade reduced the range of pressure fluctuations that can be buffered (7.5 +/-
      1.0 vs. 3.7 +/- 0.8 mmHg) while increasing the autoregulatory slope (0.10 +/-
      0.05 vs. 0.24 +/- 0.08 cm s(-1) mmHg(-1)). Furthermore, the same rate of change
      in pressure elicited a change in flow more than twice as large as at baseline.
      Thus, our results show that myogenic mechanisms play a significant role in
      cerebrovascular regulation but this may not be appreciated without adequately
      characterizing the non-linearities inherent in cerebrovascular regulation.

PMID- 23959683
TI  - Traction for low-back pain with or without sciatica.
AB  - BACKGROUND: Traction has been used to treat low-back pain (LBP), often in
      combination with other treatments. We included both manual and machine-delivered
      traction in this review. This is an update of a Cochrane review first published
      in 1995, and previously updated in 2006. OBJECTIVES: To assess the effects of
      traction compared to placebo, sham traction, reference treatments and no
      treatment in people with LBP. SEARCH METHODS: We searched the Cochrane Back
      Review Group Specialized Register, the Cochrane Central Register of Controlled
      Trials (2012, Issue 8), MEDLINE (January 2006 to August 2012), EMBASE (January
      2006 to August 2012), CINAHL (January 2006 to August 2012), and reference lists
      of articles and personal files. The review authors are not aware of any important
      new randomized controlled trial (RCTs) on this topic since the date of the last
      search. SELECTION CRITERIA: RCTs involving traction to treat acute (less than
      four weeks' duration), subacute (four to 12 weeks' duration) or chronic (more
      than 12 weeks' duration) non-specific LBP with or without sciatica. DATA
      COLLECTION AND ANALYSIS: Two review authors independently performed study
      selection, risk of bias assessment and data extraction. As there were
      insufficient data for statistical pooling, we performed a descriptive analysis.
      We did not find any case series that identified adverse effects, therefore we
      evaluated adverse effects that were reported in the included studies. MAIN
      RESULTS: We included 32 RCTs involving 2762 participants in this review. We
      considered 16 trials, representing 57% of all participants, to have a low risk of
      bias based on the Cochrane Back Review Group's 'Risk of bias' tool.For people
      with mixed symptom patterns (acute, subacute and chronic LBP with and without
      sciatica), there was low- to moderate-quality evidence that traction may make
      little or no difference in pain intensity, functional status, global improvement
      or return to work when compared to placebo, sham traction or no treatment.
      Similarly, when comparing the combination of physiotherapy plus traction with
      physiotherapy alone or when comparing traction with other treatments, there was
      very-low- to moderate-quality evidence that traction may make little or no
      difference in pain intensity, functional status or global improvement.For people
      with LBP with sciatica and acute, subacute or chronic pain, there was low- to
      moderate-quality evidence that traction probably has no impact on pain intensity,
      functional status or global improvement. This was true when traction was compared
      with controls and other treatments, as well as when the combination of traction
      plus physiotherapy was compared with physiotherapy alone. No studies reported the
      effect of traction on return to work.For chronic LBP without sciatica, there was
      moderate-quality evidence that traction probably makes little or no difference in
      pain intensity when compared with sham treatment. No studies reported on the
      effect of traction on functional status, global improvement or return to
      work.Adverse effects were reported in seven of the 32 studies. These included
      increased pain, aggravation of neurological signs and subsequent surgery. Four
      studies reported that there were no adverse effects. The remaining studies did
      not mention adverse effects. AUTHORS' CONCLUSIONS: These findings indicate that
      traction, either alone or in combination with other treatments, has little or no
      impact on pain intensity, functional status, global improvement and return to
      work among people with LBP. There is only limited-quality evidence from studies
      with small sample sizes and moderate to high risk of bias. The effects shown by
      these studies are small and are not clinically relevant. Implications for
      practice To date, the use of traction as treatment for non-specific LBP cannot be
      motivated by the best available evidence. These conclusions are applicable to
      both manual and mechanical traction. Implications for research Only new, large,
      high-quality studies may change the point estimate and its accuracy, but it
      should be noted that such change may not necessarily favour traction. Therefore,
      little priority should be given to new studies on the effect of traction
      treatment alone or as part of a package.

PMID- 23959684
TI  - Local anaesthetic sympathetic blockade for complex regional pain syndrome.
AB  - BACKGROUND: This is an update of the original Cochrane review published in The
      Cochrane Library, 2005, Issue 4, on local anaesthetic blockade (LASB) of the
      sympathetic chain used to treat complex regional pain syndrome (CRPS).
      OBJECTIVES: To assess the efficacy of LASB for the treatment of pain in CRPS and
      to evaluate the incidence of adverse effects of the procedure. SEARCH METHODS: We
      updated searches of the Cochrane Pain, Palliative and Supportive Care Group
      Specialised Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL) on the Cochrane Library (Issue 11 of 12, 2012), MEDLINE (1966 to
      22/11/12), EMBASE (1974 to 22/11/12), LILACS (1982 to 22/11/12), conference
      abstracts of the World Congresses of the International Association for the Study
      of Pain (1995 to 2010), and various clinical trial registers (inception to 2012).
      We also searched bibliographies from retrieved articles for additional studies.
      SELECTION CRITERIA: We considered for inclusion randomised controlled trials
      (RCTs) that evaluated the effect of sympathetic blockade with local anaesthetics
      in children or adults with CRPS. DATA COLLECTION AND ANALYSIS: The outcomes of
      interest were reduction in pain intensity levels, the proportion who achieved
      moderate or substantial pain relief, the duration of pain relief, and the
      presence of adverse effects in each treatment arm. MAIN RESULTS: We included an
      additional 10 studies (combined n = 363) in this update. Overall we include 12
      studies (combined n = 386). All included studies were assessed to be at high or
      unclear risk of bias.Three small studies compared LASB to placebo/sham. We were
      able to pool the results from two of these trials (intervention n = 23). Pooling
      did not demonstrate significant short-term benefit for LASB (in terms of the risk
      of a 50% reduction of pain scores).Of two studies that investigated LASB as an
      addition to rehabilitation treatment, the only study that reported pain outcomes
      demonstrated no additional benefit from LASB.Eight small randomised studies
      compared sympathetic blockade to another active intervention. Most studies found
      no difference in pain outcomes between sympathetic block and other active
      treatments.Only five studies reported adverse effects, all with minor effects
      reported. AUTHORS' CONCLUSIONS: This update has found similar results to the
      original systematic review. There remains a scarcity of published evidence to
      support the use of local anaesthetic sympathetic blockade for CRPS. From the
      existing evidence it is not possible to draw firm conclusions regarding the
      efficacy or safety of this intervention but the limited data available do not
      suggest that LASB is effective for reducing pain in CRPS.

PMID- 23959685
TI  - Structure activity relationships in alkylammonium C12-gemini surfactants used as
      dermal permeation enhancers.
AB  - The purpose of this study was to determine the ability and the safety of a series
      of alkylammonium C12-gemini surfactants to act as permeation enhancers for three
      model drugs, namely lidocaine HCl, caffeine, and ketoprofen. In vitro permeation
      studies across dermatomed porcine skin were performed over 24 h, after
      pretreating the skin for 1 h with an enhancer solution 0.16 M dissolved in
      propylene glycol. The highest enhancement ratio (enhancement ratio (ER)=5.1) was
      obtained using G12-6-12, resulting in a cumulative amount of permeated lidocaine
      HCl of 156.5 MUg cm-2. The studies with caffeine and ketoprofen revealed that the
      most effective gemini surfactant was the one with the shorter spacer, G12-2-12.
      The use of the latter resulted in an ER of 2.4 and 2.2 in the passive permeation
      of caffeine and ketoprofen, respectively. However, Azone was found to be the most
      effective permeation enhancer for ketoprofen, attaining a total of 138.4 MUg cm-2
      permeated, 2.7-fold over controls. This work demonstrates that gemini surfactants
      are effective in terms of increasing the permeation of drugs, especially in the
      case of hydrophilic ionized compounds, that do not easily cross the stratum
      corneum. Skin integrity evaluation studies did not indicate the existence of
      relevant changes in the skin structure after the use of the permeation enhancers,
      while the cytotoxicity studies allowed establishing a relative cytotoxicity
      profile including this class of compounds, single chain surfactants, and Azone. A
      dependence of the toxicity to HEK and to HDF cell lines on the spacer length of
      the various gemini molecules was found.

PMID- 23959686
TI  - Audible and infrasonic noise levels in the cabins of modern agricultural tractors
      -does the risk of adverse, exposure-dependent effects still exist?
AB  - INTRODUCTION: The agricultural tractor is one of the most commonly used vehicles
      on farms and one of the most prominent sources of noise. This article presents an
      exemplary assessment of the audible and infrasonic noise levels in the cabins of
      selected modern wheeled agricultural tractors. MATERIALS AND METHODS: Operator
      perceived audible and infrasonic noise levels in the cabins were examined for 20
      types of modern tractors during typical conditions of work. The tractors had been
      in use for no longer than 3 years, with rated power between 96 kW and 227 kW,
      designed and produced by world-renowned companies. Noise level measurements were
      performed in accordance with PN-EN ISO 9612:2011 (ISO 9612:2009). RESULTS:
      Audible noise levels (A-weighted) ranged from 62.1 to 87.4 dB-A (average: 68.2 to
      83.8 dB-A) for different work tasks. The factors influencing noise levels include
      performed tasks, soil, weather conditions and the skills of individual drivers.
      In spectrum analysis, the highest noise levels occurred at frequencies 250 Hz, 1
      and 2 kHz. Infrasound noise levels (G-weighted) ranged from 87.3 to 111.3 dB-G.
      The driver-experienced exposure to infrasound was found to increase significantly
      when the vehicle was in motion. CONCLUSIONS: Average audible noise levels have no
      potential to adversely affect the hearing organ during tasks performed inside the
      closed cabins of the analysed modern agricultural tractors. Due to the relatively
      low audible noise levels inside the cabins of modern agricultural tractors, non
      auditory effects are the only adverse symptoms that can develop. Modern
      agricultural tractors emit considerable infrasonic noise levels. All tractors
      introduced into the market should be subjected to tests with regard to infrasonic
      noise levels.

PMID- 23959687
TI  - Effort-reward imbalance at work is predicted by temporal and energetic
      characteristics of behavior: a population-based study.
AB  - OBJECTIVE: Personality dispositions may influence perceptions of work stress. The
      paper examines the relationship between temperament in terms of Strelau's
      Regulative Theory of Temperament and the effort-reward imbalance and its
      components. MATERIAL AND METHODS: There were 890 participants (360 men) aged 37.9
      years on average. Temperament traits of briskness and perseveration (temporal
      characteristics of behavior), sensory sensitivity, emotional reactivity,
      endurance and activity (energetic characteristics of behavior) were measured by
      Strelau & Zawadzki's Formal Characteristics of Behavior- Temperament Inventory
      (FCB-TI) in 1997 and 2001. Effort and reward at work were assessed with the
      original effort- reward imbalance (ERI) questionnaire of 2007. RESULTS: Higher
      ERI at work was predicted by higher emotional reactivity, higher perseveration,
      lower briskness, and lower endurance. Higher effort and lower rewards at work
      were predicted by higher perseveration and lower endurance. The FCB-TI
      temperament characteristics accounted for 5.2%, 4.8% and 6.5% of the variance in
      the ERI, effort and reward, respectively. Lower emotional reactivity, lower
      perseveration, higher brisk- ness and higher endurance predicted higher esteem at
      work, job promotion and job security. CONCLUSIONS: Individual differences in
      arousability, reflected in temporal and energetic characteristics of behavior,
      may predispose to or to protect from an effort-reward imbalance at work.
      Individual differences should be acknowledged in work stress prevention and
      developing interventions.

PMID- 23959688
TI  - The pattern of the electromagnetic field emitted by mobile phones in motor
      vehicle driving simulators.
AB  - INTRODUCTION: The paper reports the results of the determinations of UMTS EMF
      distributions in the driver's cab of motor vehicle simulators. The results will
      serve as the basis for future research on the influence of EMF emitted by mobile
      phones on driver physiology. MATERIALS AND METHODS: Two motor vehicle driving
      simulators were monitored, while an EMF source was placed at the driver's head or
      on the dashboard of the motor vehicle driving simulator. For every applied
      configuration, the maximal electric field strength was measured, as were the
      values at 16 points corresponding to chosen locations on a driver's or
      passenger's body. RESULTS: When the power was set for the maximum (49 mW), a
      value of 27 V/m was measured in the vicinity of the driver's head when the phone
      was close to the head. With the same power, when the phone was placed on the
      dashboard, the measured maximum was 15.2 V/m in the vicinity of the driver's
      foot. Similar results were obtained for the passenger. Significant perturbations
      in EMF distribution and an increase in electric field strength values in the mo
      tor vehicle driving simulator were also observed in comparison to free space
      measurements, and the electric field strength was up to 3 times higher inside the
      simulator. CONCLUSIONS: This study can act as the basis of future studies
      concerning the influence of the EMF emitted by mobile phones on the physiology of
      the driver. Additionally, the authors postulate that it is advisable to keep
      mobile phones at a distance from the head, i.e. use, whenever possible, hands
      free kits to reduce EMF exposure, both for drivers and passengers.

PMID- 23959689
TI  - Comparative analysis of whole-blood interferon-gamma and flow cytometry assays
      for detecting post-treatment immune responses in patients with active
      tuberculosis.
AB  - BACKGROUND: Intracellular cytokine flow cytometry (ICCFC) has been explored to
      detect tuberculosis (TB) infections; however, there are little data regarding its
      use to examine the dynamic responses of Mycobacterium tuberculosis (MTB)-specific
      T-cells after anti-tuberculous therapy. The aim of this study was to analyze both
      dynamic changes in functional MTB antigen-specific T-cell subsets and interferon
      gamma (IFN-gamma) levels using ICCFC and the QuantiFERON-TB Gold In-Tube (QFT-IT)
      test, respectively, following anti-tuberculous treatment in patients with active
      TB. METHODS: Twenty-six patients with active TB were enrolled in the study, and
      QFT-IT and ICCFC were performed simultaneously both before and after treatment.
      IFN-gamma levels (QFT-IT test) and the numbers of IFN-gamma- or tumor necrosis
      factor-alpha (TNF-alpha)-expressing T-cells (ICCFC assay) were examined after
      stimulation with MTB antigen. RESULTS: There was no significant reduction in the
      mean IFN-gamma concentrations measured by the QFT-IT test after anti-tuberculous
      treatment (P = 0.314). ICCFC analysis showed that the numbers of IFN-gamma(+)
      /CD4(-) T-cells, and CD4(+) T-cells producing TNF-alpha, either alone or in
      combination with IFN-gamma, were significantly reduced after anti-tuberculous
      treatment. The IFN-gamma(+) /TNF-alpha(+) /CD4(+) T-cell subset showed the
      greatest difference between untreated and treated patients with active TB (area
      under the curve = 0.734, P = 0.004). CONCLUSIONS: Unlike the QFT-IT test, ICCFC
      provides diverse immunological information about dynamic changes in the number of
      MTB antigen-specific T-cells following anti-tuberculous therapy. Thus, analysis
      of MTB antigen-stimulated T-cell responses using ICCFC might have a role to play
      in monitoring treatment responses in patients with active TB.

PMID- 23959690
TI  - Green synthesis of alpha-aminophosphonate derivatives on a solid supported TiO2 
      SiO2 catalyst and their anticancer activity.
AB  - Syntheses of a new series of biologically potent alpha-aminophosphonates were
      accomplished by one-pot Kabachnik-Fields reaction using TiO2-SiO2 as solid
      supported catalyst under microwave irradiation conditions. The chemical
      structures of all the newly synthesized compounds were confirmed by analytical
      and spectral (IR, 1H, 13C, 31P NMR, and mass) data. Their anticancer nature was
      evaluated by screening the in vitro activity on two human cancer cell lines, HeLa
      and SK-BR-3. Compounds 4i and 4o showed the best activity on these cancer cells
      even though the majority of the compounds, and particularly 4l and 4p, have good
      cytotoxic activity against them.

PMID- 23959691
TI  - Unraveling RNA-mediated networks: new insights from new technologies.
AB  - Eukaryotic gene expression is regulated in a combinatorial manner and on several
      interconnected layers, ranging from epigenetic mechanisms, transcription, RNA
      processing to protein stages. mRNA processing plays a major role in tissue- and
      development-dependent regulation, in particular alternative pre-mRNA splicing,
      which greatly enhances the capacity and composition of the proteome. Within the
      last decade, novel methods have been developed to systematically study the
      complex networks between regulatory alternative splicing factors and their RNA
      targets. This minireview focuses on cross-linking and immunoprecipitation
      methods, which - in combination with deep RNA sequencing - have made an important
      contribution in unraveling these networks.

PMID- 23959692
TI  - Making scent of the presence and local translation of odorant receptor mRNAs in
      olfactory axons.
AB  - Rodents contain in their genome more than 1000 functional odorant receptor genes,
      which are specifically expressed by the olfactory sensory neurons projecting from
      the olfactory epithelium to the olfactory bulb. Strong evidence for the presence
      and local translation of odorant receptor mRNAs in the axon of olfactory sensory
      neurons was obtained, but no function has been assigned to these axonal mRNAs
      yet. The aim of this review is to discuss the evidence for the presence and local
      translation of odorant receptor mRNAs in olfactory sensory axons, and to
      speculate on their possible function in the wiring of the mouse olfactory sensory
      projections.

PMID- 23959693
TI  - Gastric sarcomatoid carcinoma.
AB  - Sarcomatoid carcinoma is an uncommon biphasic malignant tumor of the stomach. The
      histogenesis remains unknown, and a definitive diagnosis is obtained with
      immunohistochemical staining. Since prognosis is poor after surgery, more
      effective diagnostic tools are needed in order to select the optimal therapeutic
      approach. We report the case of an old female patient presenting with an
      endophytic tumor in the gastric fundus who underwent partial resection of the
      stomach. Histology revealed a poorly differentiated adenocarcinoma component
      mixed with sarcomatoid component. Immunohistochemically, the carcinoma components
      exhibited a positive reaction to pan-cytokeratin, whereas fusiform cells showed
      positive reactions to vimentin.

PMID- 23959694
TI  - Surgical resection versus open-approach radiofrequency ablation for small
      hepatocellular carcinomas within Milan criteria after successful transcatheter
      arterial chemoembolization.
AB  - AIMS: The aim of this study was to compare the effectiveness and safety of
      hepatic resection versus open-approach RFA (ORFA) for small hepatocellular
      carcinomas (HCC) within Milan criteria after successful downstaging therapy by
      transcatheter arterial chemoembolization. MATERIAL AND METHODS: Between February
      2005 and February 2008, a total of 110 patients with advanced HCC met the Milan
      criteria after successful downstaging therapy; 58 patients then underwent hepatic
      resection and 52 received ORFA. Outcomes, including short- and long-term
      morbidity, 1-, 3-, and 5-year mortality and HCC-free survival, were analyzed and
      compared between the two groups. RESULTS: Patients in the hepatic resection and
      ORFA groups showed similar baseline characteristics and downstaging protocols.
      The ORFA group showed less blood loss, lower hospital costs, shorter surgical
      time, and fewer hospital stay days (P < 0.05). The 1-, 3-, and 5-year overall
      survival rates were 94.8, 86.2, and 79.3%, respectively, with liver resection and
      96.2, 82.7, and 76.9% with ORFA (P=0.772). The 1-, 3-, and 5-year recurrence-free
      survival rates were 93.1, 81.0, and 77.6% with resection and 94.2, 76.9, and
      73.1% with ORFA (P=0.705). The ORFA patients suffered fewer postoperative
      complications (P=0.09), particularly among the cases of central HCC (P=0.015).
      CONCLUSION: Resection and ORFA achieved similar survival benefits in the
      management of HCC within Milan criteria after successful downstaging. The
      decreased blood loss, hospital costs, surgical time, and hospital stay days, and
      lower complication rates in central cases render ORFA a preferred treatment
      option.

PMID- 23959697
TI  - Circadian rhythm and photic induction of the C-terminal splice variant of NMDAR1
      subunit in the rat suprachiasmatic nucleus.

PMID- 23959695
TI  - Physical and mental health status of Iraqi refugees resettled in the United
      States.
AB  - We conducted a survey among Iraqi refugees resettled in the United States to
      assess their physical and mental health status and healthcare access and
      utilization following the initial 8-month, post-arrival period. We randomly
      selected Iraqi refugees: >=18 years of age; living in the United States for 8-36
      months; and residents of Michigan, California, Texas and Idaho. Participants
      completed a household questionnaire and mental health assessment. We distributed
      366 surveys. Seventy-five percent of participants had health insurance at the
      time of the survey; 43 % reported delaying or not seeking care for a medical
      problem in the past year. Sixty percent of participants reported one chronic
      condition; 37 % reported >=2 conditions. The prevalence of emotional distress,
      anxiety, and depression was approximately 50 % of participants; 31 % were at risk
      for post-traumatic stress disorder. Iraqi refugees in this evaluation reported a
      high prevalence of chronic conditions and mental health symptoms despite
      relatively high access to healthcare. It is important for resettlement partners
      to be aware of the distinctive health concerns of this population to best address
      needs within this community.

PMID- 23959698
TI  - Zinc bromide promoted coupling of isonitriles with carboxylic acids to form 2,4,5
      trisubstituted oxazoles.

PMID- 23959699
TI  - Base-stabilized boryl and cationic haloborylene complexes of iron.
AB  - The synthesis of base-stabilized boryl and borylene complexes is reported. An N
      heterocyclic carbene (NHC)-stabilized iron-dihydroboryl complex was prepared by
      two different routes including methane liberation and salt elimination. A range
      of base-stabilized iron-dichloroboryl complexes was prepared by addition of Lewis
      bases to boryl complexes. Base-stabilized, cationic monochloroborylene complexes
      were synthesized from these boryl complexes by halide abstraction by using weakly
      coordinating anions. 

PMID- 23959702
TI  - Development of novel elastic vesicle-based topical formulation of cetirizine
      dihydrochloride for treatment of atopic dermatitis.
AB  - Cetirizine is a piperazine-derived second-generation antihistaminic drug
      recommended for treatment of pruritus associated with atopic dermatitis. The
      present investigation encompasses development of a nanosized novel elastic
      vesicle-based topical formulation of cetirizine dihydrochloride using combination
      of Phospholipon(r) 90G and edge activators with an aim to have targeted
      peripheral H1 antihistaminic activity. The formulation was optimized with respect
      to phospholipid/drug/charge inducer ratio along with type and concentration of
      edge activator. The optimized formulation was found to be satisfactory with
      respect to stability, drug content, entrapment efficiency, pH, viscosity,
      vesicular size, spreadability, and morphological characteristics. The ex vivo
      permeation studies through mice skin were performed using Franz diffusion cell
      assembly. It was found that the mean cumulative percentage amount permeated in 8
      h was almost twice (60.001 +/- 0.332) as compared to conventional cream (33.268
      +/- 0.795) and aqueous solution of drug (32.616 +/- 0.969), suggesting better
      penetration and permeation of cetirizine from the novel vesicular delivery
      system. Further, therapeutic efficacy of optimized formulation was assessed
      against oxazolone-induced atopic dermatitis in mice. It was observed that the
      developed formulation was highly efficacious in reducing the itching score (4.75
      itches per 20 min) compared to conventional cream (9.75 itches per 20 min) with
      profound reduction in dermal eosinophil count and erythema score. To conclude, a
      novel vesicular, dermally safe, and nontoxic topical formulation of cetirizine
      was successfully developed and may be used to treat atopic dermatitis after
      clinical investigation.

PMID- 23959703
TI  - In vitro evaluation of mucoadhesive films for gingival administration of
      lidocaine.
AB  - The aim of this study was the optimization of a lidocaine-based film formulation
      for the prevention of pain from needle prick during the injection of local
      anesthetic in dentistry. Film performances were evaluated in vitro by studying
      lidocaine permeation across pig esophageal epithelium as model for nonkeratinized
      buccal mucosa. The results obtained showed that the molecular weight of the film
      forming polymer had no effect on lidocaine transport. The introduction of the
      adhesive Plastoid(r) into the film determined a significant increase of drug
      permeation rate, which was further improved by the addition of Azone(r). On the
      contrary, the effect of sodium taurocholate was negligible.

PMID- 23959704
TI  - Antibiotic prophylaxis for the prevention of methicillin-resistant Staphylococcus
      aureus (MRSA) related complications in surgical patients.
AB  - BACKGROUND: Risk of methicillin-resistant Staphylococcus aureus (MRSA) infection
      after surgery is generally low, but affects up to 33% of patients after certain
      types of surgery. Postoperative MRSA infection can occur as surgical site
      infections (SSIs), chest infections, or bloodstream infections (bacteraemia). The
      incidence of MRSA SSIs varies from 1% to 33% depending upon the type of surgery
      performed and the carrier status of the individuals concerned. The optimal
      prophylactic antibiotic regimen for the prevention of MRSA after surgery is not
      known. OBJECTIVES: To compare the benefits and harms of all methods of antibiotic
      prophylaxis in the prevention of postoperative MRSA infection and related
      complications in people undergoing surgery. SEARCH METHODS: In March 2013 we
      searched the following databases: The Cochrane Wounds Group Specialised Register;
      The Cochrane Central Register of Controlled Trials (CENTRAL); Database of
      Abstracts of Reviews of Effects (DARE) (The Cochrane Library); NHS Economic
      Evaluation Database (The Cochrane Library); Health Technology Assessment (HTA)
      Database (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other
      Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. SELECTION CRITERIA: We
      included only randomised controlled trials (RCTs) that compared one antibiotic
      regimen used as prophylaxis for SSIs (and other postoperative infections) with
      another antibiotic regimen or with no antibiotic, and that reported the
      methicillin resistance status of the cultured organisms. We did not limit our
      search for RCTs by language, publication status, publication year, or sample
      size. DATA COLLECTION AND ANALYSIS: Two review authors independently identified
      the trials for inclusion in the review, and extracted data. We calculated the
      risk ratio (RR) with 95% confidence intervals (CI) for comparing binary outcomes
      between the groups and planned to calculated the mean difference (MD) with 95% CI
      for comparing continuous outcomes. We planned to perform meta-analysis using both
      a fixed-effect model and a random-effects model. We performed intention-to-treat
      analysis whenever possible. MAIN RESULTS: We included 12 RCTs, with 4704
      participants, in this review. Eleven trials performed a total of 16 head-to-head
      comparisons of different prophylactic antibiotic regimens. Antibiotic prophylaxis
      was compared with no antibiotic prophylaxis in one trial. All the trials were at
      high risk of bias. With the exception of one trial in which all the participants
      were positive for nasal carriage of MRSA or had had previous MRSA infections, it
      does not appear that MRSA was tested or eradicated prior to surgery; nor does it
      appear that there was high prevalence of MRSA carrier status in the people
      undergoing surgery.There was no sufficient clinical similarity between the trials
      to perform a meta-analysis. The overall all-cause mortality in four trials that
      reported mortality was 14/1401 (1.0%) and there were no significant differences
      in mortality between the intervention and control groups in each of the
      individual comparisons. There were no antibiotic-related serious adverse events
      in any of the 561 people randomised to the seven different antibiotic regimens in
      four trials (three trials that reported mortality and one other trial). None of
      the trials reported quality of life, total length of hospital stay or the use of
      healthcare resources. Overall, 221/4032 (5.5%) people developed SSIs due to all
      organisms, and 46/4704 (1.0%) people developed SSIs due to MRSA.In the 15
      comparisons that compared one antibiotic regimen with another, there were no
      significant differences in the proportion of people who developed SSIs. In the
      single trial that compared an antibiotic regimen with placebo, the proportion of
      people who developed SSIs was significantly lower in the group that received
      antibiotic prophylaxis with co-amoxiclav (or cefotaxime if allergic to
      penicillin) compared with placebo (all SSI: RR 0.26; 95% CI 0.11 to 0.65; MRSA
      SSI RR 0.05; 95% CI 0.00 to 0.83). In two trials that reported MRSA infections
      other than SSI, 19/478 (4.5%) people developed MRSA infections including SSI,
      chest infection and bacteraemia. There were no significant differences in the
      proportion of people who developed MRSA infections at any body site in these two
      comparisons. AUTHORS' CONCLUSIONS: Prophylaxis with co-amoxiclav decreases the
      proportion of people developing MRSA infections compared with placebo in people
      without malignant disease undergoing percutaneous endoscopic gastrostomy
      insertion, although this may be due to decreasing overall infection thereby
      preventing wounds from becoming secondarily infected with MRSA. There is
      currently no other evidence to suggest that using a combination of multiple
      prophylactic antibiotics or administering prophylactic antibiotics for an
      increased duration is of benefit to people undergoing surgery in terms of
      reducing MRSA infections. Well designed RCTs assessing the clinical effectiveness
      of different antibiotic regimens are necessary on this topic.

PMID- 23959705
TI  - An extended leukocyte differential count (16 types of circulating leukocytes)
      using the cytodiff flow cytometric system can provide informations for the
      discrimination of sepsis severity and prediction of outcome in sepsis patients.
AB  - Background: The Beckman Coulter CytoDiff flow cytometric system (Beckman Coulter,
      Miami, FL, USA) was recently developed for performing leukocyte differential
      counts in up to 16 leukocyte subpopulations. We compared these leukocyte
      subpopulation levels among patients with three stages of sepsis (uncomplicated
      sepsis, severe sepsis, septic shock), especially focused on the discrimination of
      complicated sepsis from uncomplicated sepsis. Methods: We examined a total of 181
      samples with sepsis who were admitted to the surgical intensive care unit. In
      addition, we examined samples obtained from 60 normal healthy volunteers. Both
      the proportions and absolute numbers of each cell type in the four groups were
      obtained using the CytoDiff flow cytometric system and compared. Results: Mature
      neutrophils and immature granulocytes failed to discriminate patients with
      complicated sepsis from those with uncomplicated sepsis although their absolute
      numbers were increased compared with normal controls. In contrast, almost all
      lymphocyte subpopulations and CD16(-) monocytes decreased significantly in
      patients with complicated sepsis compared with uncomplicated sepsis. Among them,
      only B lymphocytes showed independent ability to discriminate two groups. Both B
      lymphocytes and CD16(-) monocytes possessed a significant adverse prognostic
      impact on overall survival when their absolute numbers decreased. Conclusions:
      Almost all lymphocyte subpopulations and CD16(-) monocytes decrease in size with
      increasing sepsis severity. Among them, only B lymphocytes showed independent
      ability to discriminate patients with complicated sepsis from those with
      uncomplicated sepsis. Both B lymphocytes and CD16(-) monocytes show a significant
      adverse prognostic impact on overall survival outcomes in sepsis patients when
      their absolute numbers are decreased. (c) 2013 Clinical Cytometry Society.

PMID- 23959707
TI  - Loss of BDNF or its receptors in three mouse models has unpredictable
      consequences for anxiety and fear acquisition.
AB  - BDNF-induced signaling is essential for the development of the central nervous
      system and critical for plasticity in adults. Mature BDNF signals through TrkB,
      while its precursor proBDNF employs p75(NTR), resulting in activation of
      signaling cascades with opposite effects on neuronal survival, growth cone
      decisions, and synaptic plasticity. Accordingly, variations in the genes encoding
      BDNF and its receptors sometimes have opposing influences in psychiatric
      disorders, and despite the vast literature, consensus is lacking about the
      behavioral consequences of disrupting the activity of the BDNF system in mice. To
      dissect the behavioral traits affected by dysfunctional BDNF/TrkB vs.
      proBDNF/p75(NTR) activity, we studied Bdnf(+/-), Ntrk2(+/-), and Ngfr(-/-) mice
      in parallel with respect to exploratory behavior, anxiety, startle, and fear
      acquisition. Our data reveal that the effect of proBDNF/BDNF and its receptors on
      behavior is more complex than expected. Strikingly, receptor-deficient mice
      displayed increased risk-taking behavior in the open field and elevated plus
      maze, whereas lack of proBDNF/BDNF had the opposite effect on mouse behavior. On
      the other hand, although TrkB signaling is instrumental for acquisition of fear
      memory in an inhibitory avoidance experiment, lack of p75(NTR) or proBDNF/BDNF
      conferred increased memory in this task. Importantly, none of the genotypes
      displayed any deficits in startle reflex, indicating unimpaired response to
      shock. The combined data illustrate an apparent paradox in the role of the BDNF
      system in controlling complex behavior and suggest that the individual components
      may also engage independently in separate signaling pathways. 

PMID- 23959709
TI  - The relationship between total and regional corpus callosum atrophy, cognitive
      impairment and fatigue in multiple sclerosis patients.
AB  - OBJECTIVE: The objective of this paper is to investigate the relationship between
      total and regional corpus callosum (CC) atrophy, neuropsychological test
      performance and fatigue in multiple sclerosis (MS) patients. METHODS: We
      conducted a cross-sectional study in 113 MS patients: mean age 48 +/- 11 years,
      75/113 women, 84/113 relapsing-remitting MS, mean disease duration 21 +/- 9
      years, mean Expanded Disability Status Scale (EDSS) score 3.2 +/- 1.7. All
      patients underwent brain magnetic resonance imaging, standardised neurological
      assessment and comprehensive cognitive testing including assessments for fatigue
      and depression. Total and regional CC atrophy was assessed using the corpus
      callosum index (CCI). RESULTS: CCI correlated more strongly with T2- and T1
      lesion volume and whole brain volume than with disease duration or EDSS score.
      CCI correlated strongly with the verbal fluency test (VFT), Symbol Digit
      Modalities Test (SDMT) and Paced Auditory Serial Addition Test (PASAT).
      Multivariate regression analysis revealed that atrophy of the posterior CC
      segment was significantly associated with poor outcome in the PASAT, VFT and
      SDMT. In contrast, atrophy of the anterior CC segment was significantly
      associated with fatigue severity and poor outcome in the long-term memory test.
      CONCLUSIONS: Atrophy of the CC is associated with cognitive impairment and
      fatigue. Regional CCI results indicate that these associations are partially
      spatially segregated.

PMID- 23959706
TI  - Molecular determinants of the axonal mRNA transcriptome.
AB  - Axonal protein synthesis has been shown to play a role in developmental and
      regenerative growth, as well as in cell body responses to axotomy. Recent studies
      have begun to identify the protein products that contribute to these autonomous
      responses of axons. In the peripheral nervous system, intra-axonal protein
      synthesis has been implicated in the localized in vivo responses to neuropathic
      stimuli, and there is emerging evidence for protein synthesis in CNS axons in
      vivo. Despite that hundreds of mRNAs have now been shown to localize into the
      axonal compartment, knowledge of what RNA binding proteins are responsible for
      this is quite limited. Here, we review the current state of knowledge of RNA
      transport mechanisms and highlight recently uncovered mechanisms for dynamically
      altering the axonal transcriptome. Both changes in the levels or activities of
      components of the RNA transport apparatus and alterations in transcription of
      transported mRNAs can effectively shift the axonal mRNA population. Consistent
      with this, the axonal RNA population shifts with development, with changes in
      growth state, and in response to extracellular stimulation. Each of these events
      must impact the transcriptional and transport apparatuses of the neuron, thus
      directly and indirectly modifying the axonal transcriptome.

PMID- 23959710
TI  - Screening for neurotropic viruses in cerebrospinal fluid of patients with
      multiple sclerosis and other neurological diseases.

PMID- 23959711
TI  - Oxysterols and cholesterol precursors correlate to magnetic resonance imaging
      measures of neurodegeneration in multiple sclerosis.
AB  - BACKGROUND: Cholesterol homeostasis is important for formation and maintenance of
      myelin and axonal membranes in the central nervous system (CNS). The
      concentrations of the brain specific cholesterol metabolite 24S
      hydroxycholesterol (24OHC) and cholesterol precursors have been shown to be
      altered in multiple sclerosis (MS). However, how changes in sterol levels relate
      to the pathological processes in MS is not clear. METHODS: In this study, we
      compared serum and cerebrospinal fluid (CSF) sterol levels between 105 MS (51
      relapsing-remitting (RR); 39 secondary progressive (SP) and 15 primary
      progressive (PP)) and 49 control patients. Sterol levels were correlated to
      magnetic resonance imaging (MRI) markers of disease activity. RESULTS: We found
      decreased serum 24OHC and 27-hydroxycholesterol (27OHC) and increased CSF
      lathosterol in MS patients compared to control patients (p=0.018, p=0.002 and
      p=0.002, respectively). Subgroup analysis showed that serum 24OHC levels were
      negatively correlated to normalized brain volume measurements in relapse-onset MS
      patients (r= -0.326, p=0.004). CONCLUSIONS: These results confirm that
      cholesterol homeostasis is disturbed in MS and suggest that changes in
      cholesterol synthesis are related to neurodegenerative pathological processes as
      seen on the MRI. The data seem to be in line with the recently reported
      observation that high dose statins may have a positive effect on clinical
      disability in secondary progressive MS.

PMID- 23959708
TI  - MHC class I immune proteins are critical for hippocampus-dependent memory and
      gate NMDAR-dependent hippocampal long-term depression.
AB  - Memory impairment is a common feature of conditions that involve changes in
      inflammatory signaling in the brain, including traumatic brain injury, infection,
      neurodegenerative disorders, and normal aging. However, the causal importance of
      inflammatory mediators in cognitive impairments in these conditions remains
      unclear. Here we show that specific immune proteins, members of the major
      histocompatibility complex class I (MHC class I), are essential for normal
      hippocampus-dependent memory, and are specifically required for NMDAR-dependent
      forms of long-term depression (LTD) in the healthy adult hippocampus. In beta2m(
      /-)TAP(-/-)mice, which lack stable cell-surface expression of most MHC class I
      proteins, NMDAR-dependent LTD in area CA1 of adult hippocampus is abolished,
      while NMDAR-independent forms of potentiation, facilitation, and depression are
      unaffected. Altered NMDAR-dependent synaptic plasticity in the hippocampus of
      beta2m(-/-)TAP(-/-)mice is accompanied by pervasive deficits in hippocampus
      dependent memory, including contextual fear memory, object recognition memory,
      and social recognition memory. Thus normal MHC class I expression is essential
      for NMDAR-dependent hippocampal synaptic depression and hippocampus-dependent
      memory. These results suggest that changes in MHC class I expression could be an
      unexpected cause of disrupted synaptic plasticity and cognitive deficits in the
      aging, damaged, and diseased brain. 

PMID- 23959712
TI  - Circulating vitamin D binding protein levels are not associated with relapses or
      with vitamin D status in multiple sclerosis.
AB  - BACKGROUND: A low vitamin D status has been associated with multiple sclerosis
      (MS). Most circulating vitamin D metabolites are bound to vitamin D binding
      protein (DBP). OBJECTIVES: The purpose of this study was to explore whether there
      is an association between MS and DBP. METHODS: We compared DBP concentrations in
      blood samples of controls (n = 30) and subjects with relapsing-remitting MS
      (RRMS) during remission (n = 29) and relapse (n = 15). Furthermore, we explored
      correlations of DBP with 25- hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin
      D levels (1,25(OH)2D), and the effect of high-dose vitamin D3 supplementation on
      DBP levels in RRMS patients (n = 15). RESULTS: DBP-concentration did not differ
      between the sub-groups measured, and there was no correlation between DBP and
      vitamin D metabolite concentration within the physiological range. Upon
      supplementation of high doses vitamin D3, DBP concentration remained unaltered.
      After supplementation, serum 1,25(OH)2D(R = 0.517, p = 0.049), but not 25(OH)D,
      correlated positively with DBP. CONCLUSIONS: We found no association between DBP,
      MS, and vitamin D status within the physiological range. After high-dose vitamin
      D supplementation, DBP concentrations may be relevant for vitamin D metabolism.

PMID- 23959713
TI  - Computer-assisted rehabilitation of attention in patients with multiple
      sclerosis: results of a randomized, double-blind trial.
AB  - BACKGROUND: There is controversial information on the efficacy of cognitive
      rehabilitation in multiple sclerosis (MS). OBJECTIVE: The objective of this paper
      is to test a home-based computerized program for retraining attention dysfunction
      in MS. METHODS: Relapsing-remitting patients who failed > 2 tests of attention on
      an extensive neuropsychological battery were randomized to specific or
      nonspecific computerized training (ST, n-ST), in one-hour sessions, twice a week
      for three months. Outcome measures included neuropsychological assessment,
      depression, fatigue, everyday activities and a visual analogue scale assessing
      attentive performance (VAS). Assessments were repeated after the interventions
      and after a further three months. Statistical analysis included the analysis of
      variance (ANOVA) for repeated measures. RESULTS: Eighty-eight out of 102
      randomized patients completed the study (69 women, age 40.9 +/- 11.5 years,
      disease duration 13.0 +/- 8.7 years, Expanded Disability Status Scale score 2.7
      +/- 1.5). Fifty-five patients were randomized to ST, 33 to n-ST. A benefit of the
      ST was observed on the Paced Auditory Serial Addition Test (p < 0.002). However,
      patient self-report did not reveal differences between ST and n-ST patient
      groups. CONCLUSION: Although our program trained different attention components,
      we could detect some improvements exclusively on tasks of sustained attention.
      Moreover, patient self-perceived results may be independent of the training
      program.

PMID- 23959714
TI  - Asymptomatic lung disease caused by Mycobacterium kansasii as an opportunistic
      infection in a patient treated with natalizumab for relapsing-remitting multiple
      sclerosis.

PMID- 23959716
TI  - Role of Yersinia pestis toxin complex family proteins in resistance to
      phagocytosis by polymorphonuclear leukocytes.
AB  - Yersinia pestis carries homologues of the toxin complex (Tc) family proteins,
      which were first identified in other Gram-negative bacteria as having potent
      insecticidal activity. The Y. pestis Tc proteins are neither toxic to fleas nor
      essential for survival of the bacterium in the flea, even though tc gene
      expression is highly upregulated and much more of the Tc proteins YitA and YipA
      are produced in the flea than when Y. pestis is grown in vitro. We show that
      Tc(+) and Tc(-) Y. pestis strains are transmitted equivalently from coinfected
      fleas, further demonstrating that the Tc proteins have no discernible role,
      either positive or negative, in transmission by the flea vector. Tc proteins did,
      however, confer Y. pestis with increased resistance to killing by
      polymorphonuclear leukocytes (PMNs). Resistance to killing was not the result of
      decreased PMN viability or increased intracellular survival but instead
      correlated with a Tc protein-dependent resistance to phagocytosis that was
      independent of the type III secretion system (T3SS). Correspondingly, we did not
      detect T3SS-dependent secretion of the native Tc proteins YitA and YipA or the
      translocation of YitA- or YipA-beta-lactamase fusion proteins into CHO-K1 (CHO)
      cells or human PMNs. Thus, although highly produced by Y. pestis within the flea
      and related to insecticidal toxins, the Tc proteins do not affect interaction
      with the flea or transmission. Rather, the Y. pestis Tc proteins inhibit
      phagocytosis by mouse PMNs, independent of the T3SS, and may be important for
      subverting the mammalian innate immune response immediately following
      transmission from the flea. 

PMID- 23959715
TI  - Concise review: current status of stem cells and regenerative medicine in lung
      biology and diseases.
AB  - Lung diseases remain a significant and devastating cause of morbidity and
      mortality worldwide. In contrast to many other major diseases, lung diseases
      notably chronic obstructive pulmonary diseases (COPDs), including both asthma and
      emphysema, are increasing in prevalence and COPD is expected to become the third
      leading cause of disease mortality worldwide by 2020. New therapeutic options are
      desperately needed. A rapidly growing number of investigations of stem cells and
      cell therapies in lung biology and diseases as well as in ex vivo lung
      bioengineering have offered exciting new avenues for advancing knowledge of lung
      biology as well as providing novel potential therapeutic approaches for lung
      diseases. These initial observations have led to a growing exploration of
      endothelial progenitor cells and mesenchymal stem (stromal) cells in clinical
      trials of pulmonary hypertension and COPD with other clinical investigations
      planned. Ex vivo bioengineering of the trachea, larynx, diaphragm, and the lung
      itself with both biosynthetic constructs as well as decellularized tissues have
      been used to explore engineering both airway and vascular systems of the lung.
      Lung is thus a ripe organ for a variety of cell therapy and regenerative medicine
      approaches. Current state-of-the-art progress for each of the above areas will be
      presented as will discussion of current considerations for cell therapy-based
      clinical trials in lung diseases.

PMID- 23959717
TI  - Virulence and immune response induced by Mycobacterium avium complex strains in a
      model of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c
      mice.
AB  - The genus Mycobacterium comprises more than 150 species, including important
      pathogens for humans which cause major public health problems. The vast majority
      of efforts to understand the genus have been addressed in studies with
      Mycobacterium tuberculosis. The biological differentiation between M.
      tuberculosis and nontuberculous mycobacteria (NTM) is important because there are
      distinctions in the sources of infection, treatments, and the course of disease.
      Likewise, the importance of studying NTM is not only due to its clinical
      significance but also due to the mechanisms by which some species are pathogenic
      while others are not. Mycobacterium avium complex (MAC) is the most important
      group of NTM opportunistic pathogens, since it is the second largest medical
      complex in the genus after the M. tuberculosis complex. Here, we evaluated the
      virulence and immune response of M. avium subsp. avium and Mycobacterium
      colombiense, using experimental models of progressive pulmonary tuberculosis and
      subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high
      dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF
      alpha) and inducible nitric oxide synthase with rapid bacillus elimination and
      numerous granulomas, but without lung consolidation during late infection in
      coexistence with high expression of anti-inflammatory cytokines. In contrast,
      subcutaneous infection showed high production of the proinflammatory cytokines
      TNF-alpha and gamma interferon with relatively low production of anti
      inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently
      eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC
      infection evokes different immune and inflammatory responses depending on the MAC
      species and affected tissue. 

PMID- 23959718
TI  - The ferric enterobactin transporter Fep is required for persistent Salmonella
      enterica serovar typhimurium infection.
AB  - Most bacterial pathogens require iron to grow and colonize host tissues. The Gram
      negative bacterium Salmonella enterica serovar Typhimurium causes a natural
      systemic infection of mice that models acute and chronic human typhoid fever. S.
      Typhimurium resides in tissues within cells of the monocyte lineage, which limit
      pathogen access to iron, a mechanism of nutritional immunity. The primary ferric
      iron import system encoded by Salmonella is the siderophore ABC transporter
      FepBDGC. The Fep system has a known role in acute infection, but it is unclear
      whether ferric iron uptake or the ferric iron binding siderophores enterobactin
      and salmochelin are required for persistent infection. We defined the role of the
      Fep iron transporter and siderophores in the replication of Salmonella in
      macrophages and in mice that develop acute followed by persistent infections.
      Replication of wild-type and iron transporter mutant Salmonella strains was
      quantified in cultured macrophages, fecal pellets, and host tissues in mixed- and
      single-infection experiments. We show that deletion of fepB attenuated Salmonella
      replication and colonization within macrophages and mice. Additionally, the genes
      required to produce and transport enterobactin and salmochelin across the outer
      membrane receptors, fepA and iroN, are needed for colonization of all tissues
      examined. However, salmochelin appears to be more important than enterobactin in
      the colonization of the spleen and liver, both sites of dissemination. Thus, the
      FepBDGC ferric iron transporter and the siderophores enterobactin and salmochelin
      are required by Salmonella to evade nutritional immunity in macrophages and cause
      persistent infection in mice. 

PMID- 23959719
TI  - Analysis of autoinducer-2 quorum sensing in Yersinia pestis.
AB  - The autoinducer-2 (AI-2) quorum-sensing system has been linked to diverse
      phenotypes and regulatory changes in pathogenic bacteria. In the present study,
      we performed a molecular and biochemical characterization of the AI-2 system in
      Yersinia pestis, the causative agent of plague. In strain CO92, the AI-2 signal
      is produced in a luxS-dependent manner, reaching maximal levels of 2.5 MUM in the
      late logarithmic growth phase, and both wild-type and pigmentation (pgm) mutant
      strains made equivalent levels of AI-2. Strain CO92 possesses a chromosomal lsr
      locus encoding factors involved in the binding and import of AI-2, and confirming
      this assignment, an lsr deletion mutant increased extracellular pools of AI-2. To
      assess the functional role of AI-2 sensing in Y. pestis, microarray studies were
      conducted by comparing Deltapgm strain R88 to a Deltapgm DeltaluxS mutant or a
      quorum-sensing-null Deltapgm DeltaypeIR DeltayspIR DeltaluxS mutant at 37 degrees
      C. Our data suggest that AI-2 quorum sensing is associated with metabolic
      activities and oxidative stress genes that may help Y. pestis survive at the host
      temperature. This was confirmed by observing that the luxS mutant was more
      sensitive to killing by hydrogen peroxide, suggesting a potential requirement for
      AI-2 in evasion of oxidative damage. We also show that a large number of membrane
      protein genes are controlled by LuxS, suggesting a role for quorum sensing in
      membrane modeling. Altogether, this study provides the first global analysis of
      AI-2 signaling in Y. pestis and identifies potential roles for the system in
      controlling genes important to disease. 

PMID- 23959720
TI  - Human and animal isolates of Yersinia enterocolitica show significant serotype
      specific colonization and host-specific immune defense properties.
AB  - Yersinia enterocolitica is a human pathogen that is ubiquitous in livestock,
      especially pigs. The bacteria are able to colonize the intestinal tract of a
      variety of mammalian hosts, but the severity of induced gut-associated diseases
      (yersiniosis) differs significantly between hosts. To gain more information about
      the individual virulence determinants that contribute to colonization and
      induction of immune responses in different hosts, we analyzed and compared the
      interactions of different human- and animal-derived isolates of serotypes O:3,
      O:5,27, O:8, and O:9 with murine, porcine, and human intestinal cells and
      macrophages. The examined strains exhibited significant serotype-specific cell
      binding and entry characteristics, but adhesion and uptake into different host
      cells were not host specific and were independent of the source of the isolate.
      In contrast, survival and replication within macrophages and the induced
      proinflammatory response differed between murine, porcine, and human macrophages,
      suggesting a host-specific immune response. In fact, similar levels of the
      proinflammatory cytokine macrophage inflammatory protein 2 (MIP-2) were secreted
      by murine bone marrow-derived macrophages with all tested isolates, but the
      equivalent interleukin-8 (IL-8) response of porcine bone marrow-derived
      macrophages was strongly serotype specific and considerably lower in O:3 than in
      O:8 strains. In addition, all tested Y. enterocolitica strains caused a
      considerably higher level of secretion of the anti-inflammatory cytokine IL-10 by
      porcine than by murine macrophages. This could contribute to limiting the
      severity of the infection (in particular of serotype O:3 strains) in pigs, which
      are the primary reservoir of Y. enterocolitica strains pathogenic to humans. 

PMID- 23959722
TI  - Mucosal vaccination against tuberculosis using inert bioparticles.
AB  - Needle-free, mucosal immunization is a highly desirable strategy for vaccination
      against many pathogens, especially those entering through the respiratory mucosa,
      such as Mycobacterium tuberculosis. Unfortunately, mucosal vaccination against
      tuberculosis (TB) is impeded by a lack of suitable adjuvants and/or delivery
      platforms that could induce a protective immune response in humans. Here, we
      report on a novel biotechnological approach for mucosal vaccination against TB
      that overcomes some of the current limitations. This is achieved by coating
      protective TB antigens onto the surface of inert bacterial spores, which are then
      delivered to the respiratory tract. Our data showed that mice immunized nasally
      with coated spores developed humoral and cellular immune responses and
      multifunctional T cells and, most importantly, presented significantly reduced
      bacterial loads in their lungs and spleens following pathogenic challenge. We
      conclude that this new vaccine delivery platform merits further development as a
      mucosal vaccine for TB and possibly also other respiratory pathogens. 

PMID- 23959721
TI  - IglE is an outer membrane-associated lipoprotein essential for intracellular
      survival and murine virulence of type A Francisella tularensis.
AB  - IglE is a small, hypothetical protein encoded by the duplicated Francisella
      pathogenicity island (FPI). Inactivation of both copies of iglE rendered
      Francisella tularensis subsp. tularensis Schu S4 avirulent and incapable of
      intracellular replication, owing to an inability to escape the phagosome. This
      defect was fully reversed following single-copy expression of iglE in trans from
      attTn7 under the control of the Francisella rpsL promoter, thereby establishing
      that the loss of iglE, and not polar effects on downstream vgrG gene expression,
      was responsible for the defect. IglE is exported to the Francisella outer
      membrane as an ~13.9-kDa lipoprotein, determined on the basis of a combination of
      selective Triton X-114 solubilization, radiolabeling with [(3)H]palmitic acid,
      and sucrose density gradient membrane partitioning studies. Lastly, a genetic
      screen using the iglE-null live vaccine strain resulted in the identification of
      key regions in the carboxyl terminus of IglE that are required for intracellular
      replication of Francisella tularensis in J774A.1 macrophages. Thus, IglE is
      essential for Francisella tularensis virulence. Our data support a model that
      likely includes protein-protein interactions at or near the bacterial cell
      surface that are unknown at present. 

PMID- 23959723
TI  - Underlying mechanism of regulatory actions of diclofenac, a nonsteroidal anti
      inflammatory agent, on neuronal potassium channels and firing: an experimental
      and theoretical study.
AB  - Diclofenac (DIC), a nonsteroidal anti-inflammatory drug, is known to exert anti
      nociceptive and anti-convulsant actions; however, its effects on ion currents, in
      neurons remain debatable. We aimed to investigate (1) potential effects of
      diclofenac on membrane potential and potassium currents in differentiated NSC-34
      neuronal cells and dorsal root ganglion (DRG) neurons with whole-cell patch-clamp
      technology, and (2) firing of action potentials (APs), using a simulation model
      from hippocampal CA1 pyramidal neurons based on diclofenac's effects on potassium
      currents. In the NSC-34 cells, diclofenac exerted an inhibitory effect on delayed
      rectifier K+ current (I(KDR)) with an IC50 value of 73 MUM. Diclofenac not merely
      inhibited the I(KDR) amplitude in response to membrane depolarization, but also
      accelerated the process of current inactivation. The inhibition by diclofenac of
      IK(DR) was not reversed by subsequent application of either naloxone.
      Importantly, diclofenac (300 MUM) increased the amplitude of M-type K+ current
      (I)(KM)), while flupirtine (10 MUM) or meclofenamic acid (10 MUM) enhanced it
      effectively. Consistently, diclofenac (100 MUM) increased the amplitude of I(KM)
      and diminished the I(KDR) amplitude, with a shortening of inactivation time
      constant in DRG neurons. Furthermore, by using the simulation modeling, we
      demonstrated the potential electrophysiological mechanisms underlying changes in
      AP firing caused by diclofenac. During the exposure to diclofenac, the actions on
      both I(KM) and I(KDR) could be potential mechanism through which it influences
      the excitability of fast-spiking neurons. Caution needs to be made in attributing
      the effects of diclofenac primarily to those produced by the activation of I(KM).

PMID- 23959724
TI  - Several statins increase body and liver fat accumulation in a model of metabolic
      syndrome.
AB  - Statins are a family of drugs used in hypercholesterolemia. The aim of this study
      was to analyze the effect of statins on body and liver fat accumulation in obese
      Zucker rats. Seventy Zucker (fa/fa) rats were divided into seven groups. Rats
      from six statin groups were treated with pravastatin, simvastatin, atorvastatin,
      rosuvastatin, fluvastatin and lovastatin respectively, at a dose of 0.6 mg/kg
      body weight/day. After 6 weeks, liver and white adipose tissue from intra
      abdominal and subcutaneous locations were dissected and weighed. Subcutaneous
      adipose tissue from rosuvastatin, atorvastatin, fluvastatin and lovastatin
      treated rats was significantly increased. Fatty acid synthase (FAS) activity was
      increased by the administration of fluvastatin and lovastatin, as was glucose-6-P
      dehydrogenase (G6PDH) by the administration of atorvastatin and lovastatin. No
      changes were observed in malic enzyme (ME) activity. Furthermore, heparin
      releasable lipoprotein lipase (HR-LPL) was increased in all groups where the
      subcutaneous depot was increased, and total LPL increased only in rosuvastatin
      and fluvastatin-treated groups. With regard to liver, there were no changes in
      weight but the amount of triacylglycerols was increased in rosuvastatin group, as
      well as its liver damage was higher. In this group FAS and G6PDH activities were
      increased and no changes were observed in ME, acyl CoA oxidase (ACO) and
      carnitine palmitoyltransferase-1a (CPT-1a) activities. All statins, with the
      exception of simvastatin, worsen insulin resistance. These results show that
      statins have different effects on body fat accumulation. Moreover, rosuvastatin
      also shows a prosteatotic effect. These results should be taken into account for
      statin choice in prescription. 

PMID- 23959725
TI  - Liver X receptor agonist T0901317 enhanced peroxisome proliferator-activated
      receptor-delta expression and fatty acid oxidation in rat skeletal muscle.
AB  - Liver X receptors (LXR) have been characterized as key transcriptional regulators
      of hepatic lipid and carbohydrate metabolism. LXR are expressed also in skeletal
      muscle, however, their role in this tissue is poorly investigated and the vast
      majority of available data comes from studies on cultured myotubes. Therefore, we
      aimed to examine effects of in vivo LXR activation on muscle lipid metabolism.
      The experiments were performed on male Wistar rats fed on a standard rodent chow.
      The animals were divided into two groups (n=10) receiving either LXR activator
      (T0901317, 10 mg/kg/day) or vehicle for one week. Samples of the soleus as well
      as red and white sections of the gastrocnemius muscle were excised. T0901317
      increased muscle expression of peroxisome proliferator-activated receptor-delta
      and its target genes involved in fatty acid uptake and oxidation. In addition,
      LXR agonist enhanced palmitate oxidation (by 55%) in isolated soleus muscle.
      However, palmitate incorporation into triacylglycerol was decreased (by 38%),
      which was associated with reduced diacylglycerol acyltransferase expression (by
      66%). Despite markedly increased plasma lipid concentration upon T0901317
      treatment, muscle triacylglycerol level was elevated only in the red section of
      the gastrocnemius muscle. We conclude that T0901317 enhances muscle fatty acid
      oxidation, which prevents overt accumulation of intramuscular lipids that could
      be expected considering T0901317-induced hyperlipidemia. 

PMID- 23959726
TI  - Inactivation of mechano-sensitive dilatation upon repetitive mechanical
      stimulation of the musculo-vascular network in the rabbit.
AB  - Mechano-sensitivity of the vascular network is known to be implicated in the
      rapid dilatation at the onset of exercise, however, it is not known how this
      mechanism responds to repetitive mechanical stimulation. This study tests the
      hypothesis that the mechanically-induced hyperaemia undergoes some attenuation
      upon repetitive stimulation. Muscle blood flow was recorded from 9 masseteric
      arteries (5 right, 4 left) in 6 anesthetized rabbits. Two mechanical stimuli,
      masseter muscle compression (MC) and occlusion of the masseteric artery (AO),
      were provided in different combinations: A) repeated stimulation (0.5 Hz, for 40
      s); B) single stimuli delivered at decreasing inter-stimulus interval (ISI) from
      4 min to 2 s, C) single AO delivered before and immediately after a series of 20
      MCs at 0.5 Hz, and vice-versa. Repetitive AO stimulation at 0.5 Hz produced a
      transient hyperaemia (378 +/-189%) peaking at 4.5 +/-1.4 s and then decaying
      before the end of stimulation. The hyperaemic response to individual AOs
      progressively decreased by 74 +/-39% with decreasing ISI from 4 min to 2 s
      (p<0.01). Non significant differences were observed between AO and MC
      stimulation. Decreased response to AO was also provoked by previous repetitive MC
      stimulation, and vice-versa. The results provide evidence that the mechano
      sensitivity of the vascular network is attenuated by previous mechanical
      stimulation. It is suggested that the mechano-sensitive dilatory mechanisms
      undergoes some inactivation whose recovery time is in the order of a few minutes.

PMID- 23959727
TI  - Mechanisms of vasodilatatory effect of perivascular tissue of human internal
      thoracic artery.
AB  - It has beed showed that perivascular adipose tissue (PVAT) of human internal
      thoracic artery (ITA) releases adventitia/adipocyte-derived relaxing factor
      (ADRF). The precise mechanism of vasodilatatory effect of ADRF is still unknown.
      It was suggested that various potassium channels may be involved in the action of
      ADRF. The aim of this study was to assess the involvment of potassium channels in
      the vasorelaxing properties of ADRF in human internal thoracic artery. Human ITA
      rings were studied in vitro. First the ability of perivascular tissue of human
      ITA to release ADRF to the bath was checked. In subsequent experiments two
      fragments of skeletonised ITA were used to assess the involvement of various
      potassium channels in vasorelaxing action of PVAT. Segment of ITA, precontracted
      with serotonin (10(-5.5)M), was relaxed by adding PVAT to tissue bath, first
      without and then in the presence of appropriate potassium channel blocker. Second
      segment served as a control (no addition of PVAT). The magnitude of relaxation
      was measured and compared between preparations. This protocol was used to analyze
      the influence of iberiotoxin (100 nM), apamin (1 uM), 4-aminopyridine (1 mM, 5
      mM), BaCl2 (100 uM) and glibenclamide (10 uM). The addition of PVAT to
      precontracted skeletonized ITA caused significant vasorelaxation (54.6+/-8.03 mN
      versus 33.7+/-6.58 mN p=0.03). Similar effect was seen when 5 ml of aliquot from
      separate incubation of PVAT was added (36.3+/-5.45 mN versus 20.7+/-3.02 mN;
      p<0.001). PVAT dependent relaxation was blocked in the presence of Ca+2 dependent
      potassium channel blocker iberiotoxin (47.4+/-16.67 mN versus 43.3+/-14.54 mN;
      p=0.36) and 4-aminopyridine (5 mM) (59.3+/-3.54 mN versus 51.6+/-4.77 mN;
      p=0.12). We conclude that perivascular adipose tissue of human ITA releases
      relaxing factor that seems to act with the involvement of Ca+2 dependent
      potassium channels.

PMID- 23959728
TI  - The influence of angiotensin-(1-7) peptidomimetic (AVE 0991) and nebivolol on
      angiotensin I metabolism in aorta of apoE-knockout mice.
AB  - The detrimental role of over activation of renin-angiotensin system (RAS) in
      atherogenesis is widely recognized. Recently, we have demonstrated that Ang-(1-7)
      peptidomimetic - AVE0991, as well as known beta-adrenolytic agent nebivolol,
      exert anti-atherogenic actions in mouse model of atherosclerosis - apoE-knockout
      mice. Here, using LC-ESI-MS ex vivo system, we tested whether prolonged treatment
      of apoE-knockout mice by these drugs can influence RAS in aorta of apoE-knockout
      mice in regard to generation of most active metabolites of Ang I-Ang II and Ang
      (1-7). As compared to wild type animals there was increased generation of Ang II
      in aorta of apoE-knockout mice, while the formation of Ang-(1-7) did not differ
      between both groups. Either treatment with AVE0991 or nebivolol resulted in
      significant attenuation of Ang II production in aorta of apoE-knockout mice. In
      conclusion, for the first time we directly demonstrated that there is increase in
      ability of aortic tissue to generate Ang II in mouse model of atherosclerosis of
      apoE knockout mice, and that such effect could be efficiently attenuated either
      by treatment of nebivolol or Ang-(1-7) peptidomimetic - AVE0991. The exact
      mechanism(s) responsible for interference of both drugs with RAS require further
      investigation. 

PMID- 23959729
TI  - Haemostatic factors and intraluminal thrombus thickness in abdominal aortic
      aneurysm. Is secondary fibrinolysis relevant?
AB  - Many circulating haemostatic markers have been investigated in relation to the
      abdominal aortic aneurysm (AAA) size, growth as well as intraluminal thrombus
      (ILT) size. However, the results of these studies seem to be uncertain and
      inconsistent. The first aim of the present study was to compare the haemostatic
      parameters of fibrinolysis and some of thrombotic markers in patients with AAA
      and controls. We also examined the relationship between those parameters and both
      maximum aneurysm diameter and intraluminal thrombus thickness. Tissue plasminogen
      activator (t-PA), plasminogen activator inhibitor (PAI-1), fibrinogen (Fb), D
      dimer, prothrombin fragments 1 and 2 (F1+2), thromboxane B2 (TXB2) and lipids
      profile were measured in 36 patients with AAA and 30 controls. The mean maximum
      aortic diameter in patients with the AAA was 59+/-12 mm (range 42-100). The mean
      ILT thickness was 32+/-10 mm (range 8-56). Among haemostatic factors, t-PA and D
      dimer levels, but not PAI-1, were significantly higher in subjects with the AAA.
      There was a strong positive correlation between thickness of intraluminal
      thrombus and maximum aneurysm size (r=0.69, p<0.0001), and the negative
      relationship between t-PA and ILT thickness (r= -0.53, p=0.001) as well as
      aneurysm diameter (r= -0.38, p=0.023). Higher plasma concentrations of t-PA and D
      dimer support the hypothesis that the secondary fibrinolysis plays an important
      role in the pathogenesis of the aortic abdominal aneurysm formation. In addition,
      the negative correlation between t-PA plasma level and ILT thickness suggests
      that thrombotic/fibrinolysis imbalance may favour accelerated formation of
      intraluminal thrombus and possibly aneurysm progression. 

PMID- 23959730
TI  - Spinal transient receptor potential ankyrin 1 channel induces mechanical
      hypersensitivity, increases cutaneous blood flow, and mediates the pronociceptive
      action of dynorphin A.
AB  - We characterized pain behavior and cutaneous blood flow response induced by
      activation of the spinal transient receptor potential ankyrin 1 (TRPA1) channel
      using intrathecal drug administrations in the rat. Additionally, we assessed
      whether the pronociceptive actions induced by intrathecally administered
      dynorphin A, cholecystokinin or prostaglandin F(2alpha) are mediated by the
      spinal TRPA1 channel. Cinnamaldehyde, a TRPA1 agonist, produced a dose-related (3
      10 MUg) cutaneous blood flow increase and mechanical hypersensitivity effect.
      These effects at the currently used doses were of short duration and attenuated,
      although not completely, by pretreatment with A-967079, a TRPA1 antagonist. The
      cinnamaldehyde-induced hypersensitivity was also reduced by pretreatment with
      minocycline (an inhibitor of microglial activation), but not by carbenoxolone (a
      gap junction decoupler). In vitro study, however, indicated that minocycline only
      poorly blocks the TRPA1 channel. The mechanical hypersensitivity effect induced
      by dynorphin A, but not that by cholecystokinin or prostaglandin F(2alpha), was
      attenuated by a TRPA1 antagonist Chembridge-5861528 as well as A-967079. The
      cinnamaldehyde-induced cutaneous blood flow increase was not suppressed by MK
      801, an NMDA receptor antagonist, or bicuculline, a GABA(A) receptor antagonist.
      The results indicate that spinal TRPA1 channels promote mechanical pain
      hypersensitivity and due to antidromic activation of nociceptive nerve fibers
      increase cutaneous blood flow. The attenuation of the cinnamaldehyde-induced
      hypersensitivity effect by minocycline may be explained by action other than
      block of the TRPA1 channel. Moreover, the spinal TRPA1 channel is involved in
      mediating the pronociceptive action of dynorphin A, but not that of the spinal
      cholecystokinin or prostaglandin F(2alpha).

PMID- 23959731
TI  - Does different approach during pancreatoduodenectomy influence intestinal
      migrating myoelectrical complex recovery? Study in experimental pig model.
AB  - It is said that leaving intact the functional motor unit of the pylorus leads to
      better gastric emptying and reduces postoperative upper gut motility
      disturbances. However, despite obvious different surgical approach, both major
      pancreatoduodenectomies lead to substantial myoelectrical dysfunctions. The
      latter are not efficiently recognized. We compared Whipple and Longmire-Traverso
      procedures in terms of electromyography patterns of the upper jejunum musculature
      and the density of Cajal cells network. Twelve male weaned pigs underwent surgery
      first to implant bipolar electrodes and telemetry transmitters for continuous
      electromyography recordings and then, after 1 week recovery, to create Whipple
      (n=6) and Longmire-Traverso (n=6) pancreatoduodenectomies. The first myoelectric
      activity was already registered 1-2 hours after both operations. Time to first
      regular patterns of migrating myoelectrical complex activity was significantly
      longer in the Whipple than in the Longmire-Traverso group (68.2+/-12.9 versus
      27.8+/-51 hours, p=0.002). However, the restored patterns were substantially
      disturbed in both groups. Namely, after Longmire-Traverso operation, migrating
      myoelectrical complex cycles were very often and significantly shorter versus
      control ones, with reverse migration in the area of anastomosis while after
      Whipple procedure migrating myoelectrical complex cycles were less frequent and
      of short duration, significantly shorter in comparison even with Longmire
      Traverso group. Cajal cells network in the vicinity of anastomosis, and distally
      from it, presented greater destruction after the Whipple operation. In
      conclusion, the advantage of one of two major pancreatoduodenectomies in terms of
      myoelectrical activity correctness in upper gut has not been proved in the study.

PMID- 23959732
TI  - Melatonin and omentin: influence factors in the obstructive sleep apnoea
      syndrome?
AB  - The incidence of the obstructive sleep apnoea syndrome (OSAS) is rising as it is
      often associated with obesity. Actually, the adipose tissue is working as an
      endocrine organ with complex interactions. Recently, many adipokines such as
      omentin-1 were discovered. The role of omentin-1 in the pathogenesis of OSAS has
      not been clearly determined. Melatonin has a known influence on the sleep and
      wake rhythm. The data on the involvement of melatonin in OSAS are rare. Therefore
      we evaluated the changes in plasma levels of omentin-1 and melatonin before and
      after continuous positive airway pressure (CPAP) therapy in OSA patients. 10
      patients with newly diagnosed OSAS were included in the study. They underwent
      diagnostic polysomnography with blood drawings in a 2 hour interval for 24 hours.
      In the second night sufficient CPAP therapy was established. After three months
      of CPAP therapy the measurements were repeated. As controls 10 healthy volunteers
      were recruited. The same blood analysis and a polygraphic measurement were made
      and compared with the patients. OSA patients showed significantly higher omentin
      1 plasma levels (17.22+/-13.94 versus 9.24+/-4.85 ng/ml, p<0.05). After three
      months of therapy the plasma levels of omentin-1 decreased toward the values
      observed in the controls at 8.00 a.m. Melatonin showed the usual peak at 2.00
      a.m. in the volunteer group. OSA patients showed a later peak of melatonin at
      6.00 a.m. which returned to 2.00 a.m. after CPAP therapy. We conclude that
      omentin as well as melatonin seem to be involved in pathogenesis of OSAS. To what
      exent, further studies will have to face that question.

PMID- 23959733
TI  - Genistein affects parathyroid gland and NaPi 2a cotransporter in an animal model
      of the andropause.
AB  - This study aimed to examine the effects of genistein on the structural and
      functional changes in parathyroid glands (PTG) and sodium phosphate cotransporter
      2a (NaPi 2a) in orchidectomized rats. Sixteen-month-old Wistar rats were divided
      into sham-operated (SO), orchidectomized (Orx) and genistein-treated
      orchidectomized (Orx+G) groups. Genistein (30 mg/kg/day) was administered
      subcutaneously for 3 weeks, while the controls received vehicle alone. PTG was
      analyzed histomorphometrically, while the expressions of NaPi 2a mRNA/protein
      levels from kidneys were determined by real time PCR and Western blots. Serum and
      urine parameters were determined biochemically. The PTG volume in Orx rats was
      increased by 30% (p<0.05), compared to the SO group. Orx+G treatment increased
      the PTG volume by 35% and 75% (p<0.05) respectively, comparing to Orx and SO
      animals. Orchidectomy led to increment of serum PTH by 27% (p<0.05) compared to
      the SO group, Orx+G decreased it by 18% (p<0.05) comparing to Orx animals. NaPi
      2a expression in Orx animals was reduced in regards to its abundance in SO
      animals, although it was increased in Orx+G group compared to the Orx. Phosphorus
      urine content of Orx animals was raised by 12% (p<0.05) compared to that for the
      SO group, while Orx+G induced a 17% reduction (p<0.05) in regards to Orx animals.
      Our study shows that Orx increases PTG volume and serum PTH level, while protein
      expression of NaPi 2a is reduced. Application of genistein attenuates the
      orchidectomy-induced changes in serum PTH level, stimulates the expression of
      NaPi 2a and reduces urinary Pi excretion, implying potential beneficial effects
      on andropausal symptoms. 

PMID- 23959734
TI  - The central analgesic and anti-inflammatory activities of the methanolic extract
      of Carthamus oxycantha.
AB  - The plant extract and fractions of Carthamus oxycantha (Compositae) were assessed
      for analgesic and antiinflammatory activities. Acetic acid and formalin-induced
      nociception, hot plate and carrageenan-induced rat paw oedema tests were employed
      to evaluate the analgesic and anti-inflammatory potential of the plant extract.
      The intraperitoneal (i.p.) administration of the methanolic extract (25-30
      mg/kg), hexane (10-50 mg/kg, i.p.) and ethylacetate (50 and 100 mg/kg i.p.)
      fractions produced significant inhibition (P<0.01) of the acetic acid-induced
      writhing in mice and suppressed formalin-induced licking response of animals in
      both phases of the test. In the hot plate assay the plant extract (100 mg/kg
      i.p.) increased pain threshold of mice. Pre-treatment of animals with naloxone (5
      mg/kg i.p.) abolished the analgesic effect of the C. oxycantha in formalin and
      hot plate tests. C. oxycantha (50-200 mg/kg i.p.) produced marked anti
      inflammatory effect in carrageenan-induced rat paw edema assay comparable to
      diclofenac. These findings suggest that C. oxycantha possesses central analgesic
      and peripheral anti-inflammatory properties, with analgesic effects associated
      with the opioid system. 

PMID- 23959735
TI  - Exogenous administration of visfatin affects cytokine secretion and increases
      oxidative stress in human malignant melanoma Me45 cells.
AB  - Visfatin has recently been established as a novel adipokine that is predominantly
      expressed in visceral fat. Recombinant visfatin has immunomodulating properties,
      which can activate human leukocytes in vitro to induce cytokine production (IL
      1beta, TNF-alpha, and IL-6). Only few studies have investigated the effect of
      visfatin on prostate, breast, ovarian cancer as well as astrocytoma cell biology.
      There have been no studies on the cytokine secretion in human melanoma cells in
      response to visfatin stimulation along with intracellular protein kinases
      inhibitors. ELISA assay was performed in supernatants of Me45 cells stimulated
      with visfatin in the presence or the absence of specific pharmacological
      inhibitors of the indicated protein kinases (p38, MEK 1, PI3k and JAK kinase) and
      nuclear factor kappa B (NK-kappaB) inhibitor. Intracellular reactive oxygen
      species level was measured in 2', 7'-dichlorodihydrofluorescein diacetate (H2DCF
      DA)-loaded cells using a fluorescent measurement system. For determination of NF
      kappaB activation, activated NF-kappaB p65 subunit was determined using an EZ-TFA
      detect chemiluminescent transcription factor assay. We report that visfatin led
      to the significant increase in IL-6 and IL-8 level in culture supernatants of
      human malignant melanoma Me45 cells. Additionally visfatin resulted in the
      increase of the intracellular reactive oxygen species level. PI3k and NF-kappaB
      pathways were activated upon visfatin stimulation. The results may reflect the
      fact that PI3k pathway stimulation by visfatin may further lead to NF-kappaB
      activation and pro-inflammatory response.

PMID- 23959736
TI  - Phototherapy with low-level laser influences the proliferation of endothelial
      cells and vascular endothelial growth factor and transforming growth factor-beta
      secretion.
AB  - The healing process and the angiogenesis associated with it, is a very important
      but currently poorly understood area. Low level laser therapy (LLLT) has been
      reported to modulate the process of tissue repair by stimulation of cellular
      reaction such as migration, proliferation, apoptosis and cellular
      differentiation. The aim of this work was to evaluate the influence of laser
      radiation in the range of visible and infrared light on the proliferation of
      vascular endothelial cells in vitro and the secretion of angiogenic factors:
      vascular endothelial growth factor (VEGF)-A and transforming growth factor (TGF)
      beta. Vascular human endothelial cells (Ecs) were exposed to radiation with laser
      beam of the wavelengths: 635 nm (1.875 mW/cm2) and 830 nm (3.75 mW/cm2).
      Depending on the radiation energy density, the experiment was conducted in four
      groups : I) the control group (no radiation, 0 J/cm2); II) 635 nm - the energy
      density was 2 J/cm2; III) 635 nm - 4 J/cm2; IV635 nm - 8 J/cm2, II) 830 nm - the
      energy density was 2 J/cm2; III) 830 nm - 4 J/cm2; IV) 830 nm - 8 J/cm2. The
      proliferation and concentration of VEGF-A and TGF-beta were examined. LLLT with
      wavelength 635 nm increases endothelial cell proliferation. Significant increase
      in endothelial cell proliferation and corresponding decrease in VEGF
      concentration may suggest the role for VEGF in this process. The wavelength of
      830 nm was associated with a decrease in TGF-beta secretion.

PMID- 23959737
TI  - Dysfunctional uveoscleral pathway in a rat model of congenital glaucoma.
AB  - The purpose of the study was to investigate the presence of the uveoscleral
      pathway in the normotensive rat (NR) and in a rat model of congenital glaucoma
      (CGR). We injected the fluorescent tracer 70-kDa dextran rhodamine B in the
      anterior chamber of four NRs and four CGRs. At 10 and 60 minutes after injection,
      rats were euthanized by CO2 inhalation and eyes were enucleated. Cryosections
      were prepared and analyzed using fluorescent microscopy. Hematoxylin-eosin
      staining and electron microscopy of the anterior chamber angle (ACA) were
      performed. At 10 minutes after injection, fluorescent tracer was detected in the
      iris root and ciliary processes of NRs and CGRs. At 60 minutes, NRs showed
      prominent signal in the suprachoroidal, whereas, in the CGRs, tracer was barely
      detectable. Histology of the anterior chamber revealed the presence of an open
      ACA and electron microscopy confirmed the normal structure of the ciliary body in
      CGRs. CONCLUSIONS: Our results document the presence of an uveoscleral pathway in
      the normotensive rat. The rat model of congenital glaucoma shows severe
      impairment of the uveoscleral pathway, suggesting that alterations of the
      uveoscleral outflow might play a role in the pathogenesis of CG.

PMID- 23959738
TI  - Statins and long-term survival after isolated valve surgery: the importance of
      valve type, position and procedure.
AB  - OBJECTIVES: To investigate whether valve position, type and procedure are
      important factors in determining the beneficial effects of statin therapy with
      regard to long-term survival in patients undergoing isolated single valve
      surgery. METHODS: A prospective single-institution cardiac surgery database was
      analysed. Univariate, multivariate stepwise linear, logistic and Cox regression
      analysis and propensity matching were performed to identify if statins were
      associated with increased survival post-valve surgery. RESULTS: Overall mortality
      was 3.4% (n = 172) for all cases, n = 5013. The median follow-up was 5.8 years.
      Kaplan-Meier survival analysis indicated that statin therapy was beneficial for
      all patients undergoing isolated valve surgery, n = 5013, P = 0.03 and isolated
      aortic valve surgery, n = 3220, P = 0.03, but not isolated mitral valve surgery n
      = 1793, P = 0.4. Cox regression analysis of the study cohort revealed that statin
      therapy was a significant factors determining long-term survival in the study
      cohort, postisolated aortic valve replacement and postisolated biological aortic
      valve replacement. Statins therapy was not associated with an increased long-term
      survival post-mitral valve replacement or repair. Propensity matching resulted in
      1555 patients receiving statins being matched 1:1 with those not receiving
      statins. The results after propensity matching concurred with that of the Cox
      regression analyses, demonstrating that statin therapy was significantly
      associated with reduced in-hospital mortality, hospital length of stay and
      postoperative creatinine kinase, muscle-brain isoenzyme release. CONCLUSIONS:
      Previous publications have not distinguished valve type, position and repair as
      possible factors influencing statin-therapy outcomes. Statin therapy is
      associated with increased long-term survival postaortic valve replacement with a
      biological valve only. Statin therapy had no survival benefit in patients
      undergoing mitral valve repair or a mechanical valve replacement. A randomized
      trial is necessary to confirm or refute our findings.

PMID- 23959739
TI  - Intraoperative airway occlusion during endovascular aortic repair for ruptured
      ductal arteriosus aneurysm: rescue by jet ventilation.

PMID- 23959740
TI  - Postoperative arrhythmia in patients with bidirectional cavopulmonary
      anastomosis.
AB  - OBJECTIVES: Bidirectional cavopulmonary anastomosis (BDCPA) is part of the staged
      Fontan palliation for congenital heart defects with single-ventricle morphology.
      The aim of this study was to describe incidence and characteristics of early
      postoperative arrhythmias in patients undergoing BDCPA. METHODS: Retrospective
      analysis of 60 patients undergoing BDCPA at the age of <12 months from 2001 to
      2008 at a single centre. Arrhythmias were subclassified in sinus bradycardia,
      premature atrial/ventricular contraction, supraventricular tachycardia and
      atrioventricular block. The groups were compared according to age at operation
      and diagnosis. Postoperative follow-up data were included until Fontan
      completion. RESULTS: Postoperative arrhythmia was observed in 20 patients: 12
      temporary and 8 persisting until hospital discharge. Sinus bradycardia is a
      common postoperative arrhythmia and occurred in 16 patients (9 transient, 7
      persistent until hospital discharge). One patient undergoing BDCPA and a Damus
      Kaye-Stansel procedure had a persisting first-degree atrioventricular block. The
      occurrence of a postoperative arrhythmia was independent of age and diagnostic
      group (hypoplastic left heart vs non-hypoplasic left heart). After hospital
      discharge, five of the eight arrhythmia resolved spontaneously resulting in 2
      patients with sinus bradycardia and 1 patient with a first-degree AV block
      immediately before the Fontan completion was undertaken. CONCLUSIONS:
      Postoperative arrhythmias in patients with BDCPA occur early after surgery and
      are temporary. Severe and life-threatening arrhythmias are rare although the
      interventions are complex and the patients very young. The most common arrhythmia
      is sinus bradycardia.

PMID- 23959741
TI  - True aneurysm of the peripheral pulmonary artery due to necrotizing giant cell
      arteritis.
AB  - Pulmonary artery aneurysm in adults is a rare diagnosis. Most cases described in
      the literature are either associated with congenital heart disease or pulmonal
      arterial hypertension, respectively, or are not true aneurysms but rather
      pseudoaneurysms, which are usually iatrogenic. We present the case of a 68-year
      old female patient with the incidental finding of a true aneurysm of the right
      peripheral pulmonary artery with a maximum diameter of 4 cm. With increasing
      aneurysm diameter over time, the decision for a surgical resection was made.
      Complete resection of the aneurysm including lower lobe resection was performed.
      Histopathological examination showed necrotizing giant cell arteritis as the
      underlying cause. The postoperative course was uneventful and no signs of further
      disease activity were detected. To our knowledge, this is the first reported case
      of a pulmonary artery aneurysm caused by giant cell arteritis, whereas it should
      be noted that the distinction between Takayasu arteritis and giant cell arteritis
      is not clearly defined. Considering the high mortality associated with aneurysm
      rupture, surveillance is advocated for small aneurysms, whereas for larger
      aneurysms and those showing signs of progression in size despite medical therapy
      or even dissection, surgical intervention should be considered. 

PMID- 23959742
TI  - Pulmonary rehabilitation programme for patients undergoing curative lung cancer
      surgery.
AB  - OBJECTIVES: The aim of the study was to develop a multistranded pragmatic
      rehabilitation programme for operable lung cancer patients, that looks into
      feasibility, process indicators, outcome measures, local adaptability, compliance
      and potential cost benefit. METHODS: An outpatient-based complex intervention,
      rehabilitation for operated lung cancer (ROC) programme, was developed to
      optimize physical status, prepare for the inpatient journey and support through
      recovery after surgery. It includes exercise classes, smoking cessation, dietary
      advice and patient education and was tested in an enriched cohort study within a
      regional thoracic unit over 18 months. RESULTS: A multistranded pragmatic
      rehabilitation programme pre- and post-surgery is feasible. Fifty-eight patients
      received the intervention and 305 received standard care. Both groups were
      matched for age, lung function comorbidity and type of surgery. Patients in the
      intervention group attended exercise classes twice a week until surgery, which
      was not delayed. Patients attended four sessions presurgery (range 1-15),
      resulting in an improvement of 20 m (range -73-195, P = 0.001) in a 6-min walk
      test and 0.66 l in forced expiratory volume in 1 s (range -1.85 from 1.11, P =
      0.009) from baseline to presurgery. Fifty-four percentage of smokers in the
      intervention group stopped smoking. Sixteen percentage of patients were
      identified as being at risk of malnourishment and received nutritional
      intervention. There was a trend in patients in the intervention group towards
      experiencing fewer postoperative pulmonary complications than those in the non
      intervention group (9 vs 16%, respectively, P = 0.21) and fewer readmissions to
      hospital because of complications (5 vs 14% respectively, P = 0.12). CONCLUSION:
      Chronic obstructive pulmonary disease-type pulmonary rehabilitation before and
      after lung cancer surgery is viable, and preliminary results suggest improvement
      in physical measures. A multicentre, randomized controlled trial is warranted to
      confirm clinical efficacy. ISRCTN REGISTRATION NUMBER: ISRCTN00061628.

PMID- 23959743
TI  - Early results of a novel technique for ring-reinforced aortic valve and root
      restoration.
AB  - OBJECTIVES: Surgery for aortic root aneurysm without valve stenosis is
      increasingly being transformed from the Bentall procedure to valve-sparing aortic
      root remodelling or reimplantation. In this report, a new repair option is
      explored, with full functional 'restoration' of the aortic root complex using a
      geometric annuloplasty ring, leaflet repair, and sinus/ascending aortic
      replacement with a Valsalva graft. METHODS: The geometric annuloplasty ring
      restores elliptical annular shape and size in patients with tri-leaflet aortic
      insufficiency (AI). The ring mounts the three valve commissures on 10 degrees 
      outwardly flaring posts, and facilitates required leaflet procedures. In clinical
      application, the device has been effective in achieving stable AI reduction with
      low valve gradients. In this report, 6 patients with aortic root aneurysms and
      moderate/severe AI were managed with valve repair using the annuloplasty device
      and leaflet reconstruction, and then concomitant sinus and ascending aortic graft
      replacement with coronary implantation. RESULTS: In the 6 initial root aneurysm
      patients, there were no in-hospital mortalities, procedural conversions, or valve
      related complications. Preoperative AI grade was 2-4 and fell to 0-1
      postoperatively. Post-repair mean systolic gradients ranged from 7 to 12 mmHg,
      and all patients had stable intermediate-term valve function. CONCLUSIONS: Aortic
      root restoration using a geometric annuloplasty ring and Valsalva graft may be
      the most physiological method of aortic valve repair and root replacement. Even
      with severe leaflet derangements, valve sparing can be achieved with good
      competence and potentially stable long-term results. This technique could assist
      in extending valve sparing into most categories of aortic root disease. CLINICAL
      TRIALS: Patients were managed as part of a Phase I (ClinicalTrials.gov
      Identifier: NCT01400841), supported by BioStable Science and Engineering (BSE),
      Austin, TX, USA; www.biostable-s-e.com.

PMID- 23959744
TI  - Religious perspectives on the use of psychopharmaceuticals as an enhancement
      technology.
AB  - The use of psychopharmaceuticals as an enhancement technology has been the focus
      of attention in the bioethics literature. However, there has been little
      examination of the challenges that this practice creates for religious traditions
      that place importance on questions of being, authenticity, and identity. We asked
      expert commentators from six major world religions to consider the issues raised
      by psychopharmaceuticals as an enhancement technology. These commentaries reveal
      that in assessing the appropriate place of medical therapies, religious
      traditions, like secular perspectives, rely upon ideas about health and disease
      and about normal human behavior. But unlike secular perspectives, faith
      traditions explicitly concern themselves with ways in which medicine should or
      should not be used to live a "good life".

PMID- 23959746
TI  - Visiting.

PMID- 23959745
TI  - Using the AUDIT-PC to predict alcohol withdrawal in hospitalized patients.
AB  - BACKGROUND: Alcohol withdrawal syndrome (AWS) occurs when alcohol-dependent
      individuals abruptly reduce or stop drinking. Hospitalized alcohol-dependent
      patients are at risk. Hospitals need a validated screening tool to assess
      withdrawal risk, but no validated tools are currently available. OBJECTIVE: To
      examine the admission Alcohol Use Disorders Identification Test-(Piccinelli)
      Consumption (AUDIT-PC) ability to predict the subsequent development of AWS among
      hospitalized medical-surgical patients admitted to a non-intensive care setting.
      DESIGN: Retrospective case-control study of patients discharged from the hospital
      with a diagnosis of AWS. All patients with AWS were classified as presenting with
      AWS or developing AWS later during admission. Patients admitted to an intensive
      care setting and those missing AUDIT-PC scores were excluded from analysis. A
      hierarchical (by hospital unit) logistic regression was performed and receiver
      operating characteristics were examined on those developing AWS after admission
      and randomly selected controls. Because those diagnosing AWS were not blinded to
      the AUDIT-PC scores, a sensitivity analysis was performed. PARTICIPANTS: The
      study cohort included all patients age >=18 years admitted to any medical or
      surgical units in a single health care system from 6 October 2009 to 7 October
      2010. KEY RESULTS: After exclusions, 414 patients were identified with AWS. The
      223 (53.9 %) who developed AWS after admission were compared to 466 randomly
      selected controls without AWS. An AUDIT-PC score >=4 at admission provides 91.0 %
      sensitivity and 89.7 % specificity (AUC=0.95; 95 % CI, 0.94-0.97) for AWS, and
      maximizes the correct classification while resulting in 17 false positives for
      every true positive identified. Performance remained excellent on sensitivity
      analysis (AUC=0.92; 95 % CI, 0.90-0.93). Increasing AUDIT-PC scores were
      associated with an increased risk of AWS (OR=1.68, 95 % CI 1.55-1.82, p<0.001).
      CONCLUSIONS: The admission AUDIT-PC score is an excellent discriminator of AWS
      and could be an important component of future clinical prediction rules.
      Calibration and further validation on a large prospectivecohort is indicated.

PMID- 23959747
TI  - Human DNA ligases: a comprehensive new look for cancer therapy.
AB  - Living organisms belonging to all three domains of life, viz., eubacteria,
      archaeabacteria, and eukaryotes encode one or more DNA ligases. DNA ligases are
      indispensable in various DNA repair and replication processes and a deficiency or
      an inhibition of their activity can lead to accumulation of DNA damage and strand
      breaks. DNA damage, specially strand breaks at unsustainable levels can lead to
      replication block and/or cell death. DNA ligases as potential anticancer targets
      have been realized only recently. There is enough rationale to suggest that
      ligases have a tremendous potential for novel therapeutics including anticancer
      and antibacterial therapy, specially when the world is facing acute problems of
      drug resistance and chemotherapy failure, with an immediate need for new
      therapeutic targets. Here, we review the current state of the art in the
      development of human ligase inhibitors, their structures, molecular mechanisms,
      physiological effects, and their potential in future cancer therapy. Citing
      examples, we focus on strategies for improving the activity and specificity of
      existing and novel inhibitors by using structure-based rational approaches. In
      the end, we describe potential new sites on the ligase I protein that can be
      targeted for the development of novel inhibitors. This is the first comprehensive
      review to compile all known human ligase inhibitors and to provide a rationale
      for the further development of ligase inhibitors for cancer therapy. 

PMID- 23959748
TI  - Road traffic injury mortality and its mechanisms in India: nationally
      representative mortality survey of 1.1 million homes.
AB  - OBJECTIVES: To quantify and describe the mechanism of road traffic injury (RTI)
      deaths in India. DESIGN: We conducted a nationally representative mortality
      survey where at least two physicians coded each non-medical field staff's verbal
      autopsy reports. RTI mechanism data were extracted from the narrative section of
      these reports. SETTING: 1.1 million homes in India. PARTICIPANTS: Over 122 000
      deaths at all ages from 2001 to 2003. PRIMARY AND SECONDARY OUTCOME MEASURES: Age
      specific and sex-specific mortality rates, place and timing of death, modes of
      transportation and injuries sustained. RESULTS: The 2299 RTI deaths in the survey
      correspond to an estimated 183 600 RTI deaths or about 2% of all deaths in 2005
      nationally, of which 65% occurred in men between the ages 15 and 59 years. The
      age-adjusted mortality rate was greater in men than in women, in urban than in
      rural areas, and was notably higher than that estimated from the national police
      records. Pedestrians (68 000), motorcyclists (36 000) and other vulnerable road
      users (20 000) constituted 68% of RTI deaths (124 000) nationally. Among the
      study sample, the majority of all RTI deaths occurred at the scene of collision
      (1005/1733, 58%), within minutes of collision (883/1596, 55%), and/or involved a
      head injury (691/1124, 62%). Compared to non-pedestrian RTI deaths, about 55 000
      (81%) of pedestrian deaths were associated with less education and living in
      poorer neighbourhoods. CONCLUSIONS: In India, RTIs cause a substantial number of
      deaths, particularly among pedestrians and other vulnerable road users.
      Interventions to prevent collisions and reduce injuries might address over half
      of the RTI deaths. Improved prehospital transport and hospital trauma care might
      address just over a third of the RTI deaths.

PMID- 23959749
TI  - Trends in ischaemic heart disease hospitalisation and case fatality in the Hong
      Kong Chinese population 2000-2009: a secondary analysis.
AB  - OBJECTIVES: This study examines the recent trends in ischaemic heart disease
      (IHD) incidence and case fatality in Hong Kong and explores the possible risk
      factors. DESIGN: Retrospective observational study. SETTING: All public hospitals
      in Hong Kong. OUTCOME MEASURES: Incidence rate was defined as the number of IHD
      inpatient episodes divided by the size of the corresponding population. Short
      term and long-term case fatality rate was defined as deaths from all causes
      occurring within 30 and 31-365 days, respectively, divided by the number of IHD
      inpatient episodes among the corresponding population. METHODS: Poisson and
      logistic regression models were used to examine the IHD incidence and short
      term/long-term case fatality trends, respectively, for different age and sex
      groups. RESULTS: IHD incidence was stable in most age groups. However, the
      incidence in men aged 15-24, 35-44 and >=85 years showed increasing trends,
      whereas the incidence in men aged 55-64 years and women aged 35-74 years showed
      decreasing trends. Overall, the short-term/long-term case fatality rates were
      unchanged over time for both sexes. Short-term case fatality showed increasing
      trends in women aged 65-74 and >=85 years, while long-term case fatality in men
      aged 55-64 and 75-84 years and women aged >=75 years showed increasing trends.
      CONCLUSIONS: Hong Kong trends resembled those in the USA, England and Wales,
      showing stable or slow decline in the IHD rates, while increasing trends were
      observed for some age groups, particularly young adults. Public health promotion
      efforts should focus on reducing cardiovascular risk factors, such as
      hypertension prevalence.

PMID- 23959750
TI  - The persistence of adolescent binge drinking into adulthood: findings from a 15
      year prospective cohort study.
AB  - OBJECTIVES: To examine the prevalence of binge drinking in adolescence and its
      persistence into adulthood in an Australian cohort. DESIGN: 15-year prospective
      cohort study. SETTING: Victoria, Australia. PARTICIPANTS: 1943 adolescents were
      recruited from secondary schools at age 14-15 years. PRIMARY OUTCOME MEASURES:
      Levels of past-week 'binge' drinking (5+ standard drinks on a day, each 10 g
      alcohol) and 'heavy binge' drinking (20+ standard drinks on a day for males, 11+
      for females) were assessed during six adolescent waves, and across three adult
      waves up to age 29 years. RESULTS: Half of the males (52%) and a third of the
      females (34%) reported past-week adolescent binge drinking. 90% of male and 70%
      of female adolescent-onset binge drinkers continued to binge in young adulthood;
      70% of males and 48% of females who were not adolescent-onset binge drinkers
      reported young adult binge drinking. Past-week heavy bingeing was less common in
      adolescence than adulthood. Overall, 35% of the sample (95% CI 33% to 38%)
      reported past-week binge drinking in adolescence and young adulthood and one
      third (33%; 30% to 35%) first reported binge drinking in young adulthood; only 7%
      of the sample (6-8%) had binge drinking in adolescence but not young adulthood.
      'Heavy binge' drinking occurred in adolescence and young adulthood for 9% (8% to
      10%); 8% (7% to 10%) reported it in adolescence but no longer in young adulthood;
      and 24% (22% to 26%) began 'heavy binge' drinking in young adulthood. Among
      adolescent binge drinkers (n=821), young adult binge and heavy binge drinking
      were predicted by being male, adolescent antisocial behaviour and adverse
      consequences of drinking in adolescence. CONCLUSIONS: Binge alcohol use is common
      and persistent among young Australians. Efforts to prevent the onset of binge
      drinking during adolescence may substantially reduce harmful patterns of alcohol
      use in young adulthood.

PMID- 23959751
TI  - Associations of metabolic factors and adipokines with pain in incipient upper
      extremity soft tissue disorders: a cross-sectional study.
AB  - OBJECTIVES: Earlier studies have suggested associations between metabolic factors
      and musculoskeletal pain or disorders. We studied the associations of obesity,
      lipids, other features of the metabolic syndrome and adipokines (adiponectin,
      leptin, resistin, visfatin) with upper extremity pain in a clinical population
      with incipient upper extremity soft tissue disorders (UESTDs). DESIGN: A cross
      sectional study. SETTING: Primary healthcare (occupational health service) with
      further examinations at a research institute. PARTICIPANTS: Patients (N=163, 86%
      were women) seeking medical advice in the occupational health service due to
      incipient upper extremity symptoms with symptom duration of <1 month were
      referred for consultation to the Finnish Institute of Occupational Health from
      Spring 2006 to Fall 2008. We included all actively working subjects meeting
      diagnostic criteria based on physical examination. We excluded subjects meeting
      predetermined conditions. OUTCOME MEASURE: Pain intensity was assessed with
      visual analogue scale and dichotomised at the highest tertile (cut-point 60).
      RESULTS: Obesity (adjusted OR for high waist circumference 2.9, 95% CI 1.1 to
      7.3), high-density lipoprotein cholesterol (OR 3.9, 95% CI 1.4 to 10.1 for low
      level) and triglycerides (OR 2.6, 95% CI 1.0 to 6.8 for high level) were
      associated with pain intensity. Of four adipokines studied, only visfatin was
      associated with upper extremity pain (adjusted OR 1.4, 95% CI 1.0 to 2.1 for 1SD
      increase in level). CONCLUSIONS: Abdominal obesity and lipids may have an impact
      on pain intensity in UESTDs. They may intensify pain through proinflammatory pain
      modifying molecular pathways or by causing soft tissue pathology and dysfunction
      of their supplying arteries. Of four adipokines studied only one (visfatin) was
      associated with pain intensity. In the future, further studies are required to
      better understand the relationship between metabolic factors and UESTDs.

PMID- 23959752
TI  - Ulcer healing time and antibiotic treatment before and after the introduction of
      the Registry of Ulcer Treatment: an improvement project in a national quality
      registry in Sweden.
AB  - OBJECTIVES: To investigate changes in ulcer healing time and antibiotic treatment
      in Sweden following the introduction of the Registry of Ulcer Treatment (RUT), a
      national quality registry, in 2009. DESIGN: A statistical analysis of RUT data
      concerning the healing time and antibiotic treatment for patients with hard-to
      heal ulcers in Sweden between 2009 and 2012. SETTING: RUT is a national web-based
      quality registry used to capture areas of improvement in ulcer care and to
      structure wound management by registering patients with hard-to-heal leg, foot
      and pressure ulcers. Registration includes variables such as gender, age,
      diagnosis, healing time, antibiotic treatment, and ulcer duration and size.
      POPULATION: Every patient with a hard-to-heal ulcer registered with RUT between
      2009 and 2012 (n=1417) was included. MAIN OUTCOME MEASURES: Statistical analyses
      were performed using Stata V.12.1. Healing time was assessed with the Kaplan
      Meier analysis and adjustment was made for ulcer size. A log-rank test was used
      for equality of survivor functions. RESULTS: According to the adjusted registry
      in December 2012, patients' median age was 80 years (mean 77.5 years, range 11
      103 years). The median healing time for all ulcers, adjusted for ulcer size, was
      146 days (21 weeks) in 2009 and 63 days (9 weeks) in 2012 (p=0.001). Considering
      all years between 2009 and 2012, antibiotic treatment for patients with hard-to
      heal ulcers was reduced from 71% before registration to 29% after registration of
      ulcer healing (p=0.001). CONCLUSIONS: Healing time and antibiotic treatment
      decreased significantly during 3 years after launch of RUT.

PMID- 23959753
TI  - IL-6 pathway-driven investigation of response to IL-6 receptor inhibition in
      rheumatoid arthritis.
AB  - OBJECTIVES: To determine whether heterogeneity in interleukin-6 (IL-6), IL-6
      receptor and other components of the IL-6 signalling pathway/network, at the
      gene, transcript and protein levels, correlate with disease activity in patients
      with rheumatoid arthritis (RA) and with clinical response to tocilizumab. DESIGN:
      Biomarker samples and clinical data for five phase 3 trials of tocilizumab were
      analysed using serum (3751 samples), genotype (927 samples) and transcript (217
      samples) analyses. Linear regression was then used to assess the association
      between these markers and either baseline disease activity or treatment response.
      RESULTS: Higher baseline serum IL-6 levels were significantly associated
      (p<0.0001) with higher baseline DAS28, erythrocyte sedimentation rate, C reactive
      protein and Health Assessment Questionnaire in patients whose responses to
      disease-modifying antirheumatic drugs (DMARD-IR) and to antitumour necrosis
      factor (aTNF-IR) were inadequate and patients who were naive/responders to
      methotrexate (MTX). Higher baseline serum IL-6 levels were also significantly
      associated with better clinical response to tocilizumab (versus placebo) measured
      by cDAS28 in the pooled DMARD-IR (p<0.0001) and MTX-naive populations (p=0.04).
      However, the association with treatment response was weak. A threefold difference
      in baseline IL-6 level corresponded to only a 0.17-unit difference in DAS28 at
      week 16. IL-6 pathway single nucleotide polymorphisms and RNA levels also were
      not strongly associated with treatment response. CONCLUSIONS: Our analyses
      illustrate that the biological activity of a disease-associated molecular pathway
      may impact the benefit of a therapy targeting that pathway. However, the
      variation in pathway activity, as measured in blood, may not be a strong
      predictor. These data suggest that the major contribution to variability in
      clinical responsiveness to therapeutics in RA remains unknown.

PMID- 23959754
TI  - Barriers to, and facilitators in, introducing integrated diabetes care in
      Ireland: a qualitative study of views in general practice.
AB  - OBJECTIVE: To examine the barriers to, and facilitators in, improving diabetes
      management from the general practice perspective, in advance of the
      implementation of an integrated model of care in Ireland. DESIGN: Qualitative
      using semistructured interviews. SETTING: Primary care in the Republic of
      Ireland. PARTICIPANTS: Purposive sample of 29 general practitioners (GPs) and two
      practice nurses. METHODS: Data were analysed using a framework approach. RESULTS:
      The main barriers and facilitators occurred at the level of the health system but
      had a ripple effect at an organisational, professional and patient level. The
      lack of targeted remuneration for diabetes management in the Irish health system
      created apathy in general practice and was perceived to be indicative of the lack
      of value placed on chronic disease management in the health system. There were
      'pockets of interest' among GPs motivated by 'vocational' incentives such as a
      sense of professional duty; however, this was not sufficient to drive widespread
      improvement. The hospital service was seen as an essential support for primary
      care management, although some participants referred to emerging tension between
      settings. The lack of coordination at the primary-secondary interface resulted in
      avoidable duplication and an 'in the meantime' period of uncertainty around when
      patients would be called or recalled by specialist services. Facilitators
      included the availability of nursing support and serendipitous access to
      services. The lack of resources in the community was considered to be at odds
      with policy to shift routine management to general practice, which is fast
      reaching saturation. CONCLUSIONS: At present, intrinsic motivation is driving the
      improvement of diabetes care in Ireland. This will not be sufficient to implement
      the proposed reform including a national model of integrated care. Policymakers
      need to assess and prepare for the disparate levels of interest and
      infrastructure in primary care in Ireland to support this change.

PMID- 23959755
TI  - Is teenage pregnancy an obstetric risk in a welfare society? A population-based
      study in Finland, from 2006 to 2011.
AB  - OBJECTIVE: To assess obstetric outcomes in teenage pregnancies in a country with
      a low teenage delivery rate and comprehensive high-quality prenatal care. DESIGN:
      Retrospective population-based register study. SETTING: Finland. PARTICIPANTS:
      All nulliparous teenagers (13-15 years (n=84), 16-17 years (n=1234), 18-19 years
      (n=5987)) and controls (25-year-old to 29-year-old women (n=51 142)) with
      singleton deliveries in 2006-2011. MAIN OUTCOME MEASURES: Risk of adverse
      obstetric outcomes adjusted for demographic factors and clinically relevant
      pregnancy complications, with main focus on maternal pregnancy complications.
      RESULTS: Teenage mothers were more likely than controls to live in rural areas
      (16% (n=1168) vs 11.8% (n=6035)), smoke (36.4% (n=2661) vs 7% (n=3580)) and
      misuse alcohol or drugs (1.1% (n=82) vs 0.2% (n=96); p<0.001 for all). Teenagers
      made a good mean number of antenatal clinic visits (16.4 vs 16.5), but were more
      likely to have attended fewer than half of the recommended visits (3% (n=210) vs
      1.4% (n=716)). Teenagers faced increased risks of several obstetric
      complications, for example, anaemia (adjusted OR 1.8, 95% CI 1.6 to 2.1),
      proteinuria (1.8, 1.2 to 2.6), urinary tract infection (UTI; 2.9, 1.8 to 4.8),
      pyelonephritis (6.3, 3.8 to 10.4) and eclampsia (3.2, 1.4 to 7.3), the risks
      increasing with descending age for most outcomes. Elevated risks of pre-eclampsia
      (3.7, 1.5 to 9.0) and preterm delivery (2.5, 1.2 to 5.3) were also found among 13
      year-olds to 15-year-olds. However, teenage mothers were more likely to have
      vaginal delivery (1.9, 1.7 to 2.0) without complications. Inadequate prenatal
      care among teenagers was a risk factor of eclampsia (12.6, 2.6 to 62.6), UTI
      (5.8, 1.7 to 19.7) and adverse neonatal outcomes. CONCLUSIONS: Pregnant teenagers
      tended to be socioeconomically disadvantaged versus controls and faced higher
      risks of various pregnancy complications. Special attention should be paid to
      enrolling teenagers into adequate prenatal care in early pregnancy.

PMID- 23959756
TI  - Surgical Intensive Care Unit Optimal Mobilisation Score (SOMS) trial: a protocol
      for an international, multicentre, randomised controlled trial focused on goal
      directed early mobilisation of surgical ICU patients.
AB  - INTRODUCTION: Immobilisation in the intensive care unit (ICU) leads to muscle
      weakness and is associated with increased costs and long-term functional
      disability. Previous studies showed early mobilisation of medical ICU patients
      improves clinical outcomes. The Surgical ICU Optimal Mobilisation Score (SOMS)
      trial aims to test whether a budget-neutral intervention to facilitate goal
      directed early mobilisation in the surgical ICU improves participant mobilisation
      and associated clinical outcomes. METHODS AND ANALYSIS: The SOMS trial is an
      international, multicentre, randomised clinical study being conducted in the USA
      and Europe. We are targeting 200 patients. The primary outcome is average daily
      SOMS level and key secondary outcomes are ICU length of stay until discharge
      readiness and 'mini' modified Functional Independence Measure (mmFIM) at hospital
      discharge. Additional secondary outcomes include quality of life assessed at 3
      months after hospital discharge and global muscle strength at ICU discharge.
      Exploratory outcomes will include: ventilator-free days, ICU and hospital length
      of stay and 3-month mortality. We will explore genetic influences on the
      effectiveness of early mobilisation and centre-specific effects of early
      mobilisation on outcomes. ETHICS AND DISSEMINATION: Following Institutional
      Review Board (IRB) approval in three institutions, we started study recruitment
      and plan to expand to additional centres in Germany and Italy. Safety monitoring
      will be the domain of the Data and Safety Monitoring Board (DSMB). The SOMS trial
      will also explore the feasibility of a transcontinental study on early
      mobilisation in the surgical ICU. RESULTS: The results of this study, along with
      those of ancillary studies, will be made available in the form of manuscripts and
      presentations at national and international meetings. REGISTRATION: This study
      has been registered at clinicaltrials.gov (NCT01363102).

PMID- 23959757
TI  - Do men consult less than women? An analysis of routinely collected UK general
      practice data.
AB  - OBJECTIVE: To examine whether gender differences in primary care consultation
      rates (1) vary by age and deprivation status and (2) diminish when consultation
      for reproductive reasons or common underlying morbidities are accounted for.
      DESIGN: Cross-sectional study of a cohort of patients registered with general
      practice. SETTING: UK primary care. SUBJECTS: Patients (1 869 149 men and 1 916
      898 women) registered with 446 eligible practices in 2010. PRIMARY OUTCOME
      MEASURES: Primary care consultation rate. RESULTS: This study analyses routinely
      collected primary care consultation data. The crude consultation rate was 32%
      lower in men than women. The magnitude of gender difference varied across the
      life course, and there was no 'excess' female consulting in early and later life.
      The greatest gender gap in primary care consultations was seen among those aged
      between 16 and 60 years. Gender differences in consulting were higher in people
      from more deprived areas than among those from more affluent areas. Accounting
      for reproductive-related consultations diminished but did not eradicate the
      gender gap. However, consultation rates in men and women who had comparable
      underlying morbidities (as assessed by receipt of medication) were similar; men
      in receipt of antidepressant medication were only 8% less likely to consult than
      women in receipt of antidepressant medication (relative risk (RR) 0.916, 95% CI
      0.913 to 0.918), and men in receipt of medication to treat cardiovascular disease
      were just 5% less likely to consult (RR=0.950, 95% CI 0.948 to 0.952) than women
      receiving similar medication. These small gender differences diminished further,
      particularly for depression (RR=0.950, 95% CI 0.947 to 0.953), after also taking
      account of reproductive consultations. CONCLUSIONS: Overall gender differences in
      consulting are most marked between the ages of 16 and 60 years; these differences
      are only partially accounted for by consultations for reproductive reasons.
      Differences in consultation rates between men and women were largely eradicated
      when comparing men and women in receipt of medication for similar underlying
      morbidities.

PMID- 23959758
TI  - Protocol for a qualitative study of knowledge translation in a participatory
      research project.
AB  - INTRODUCTION: In this article, we present a methodological design for qualitative
      investigation of knowledge translation (KT) between participants in a
      participatory research project. In spite of a vast expansion of conceptual models
      and frameworks for conducting KT between research and practice, few models
      emphasise how KTs come about. Better understanding of the actions and activities
      involved in a KT process is important for promoting diffusion of knowledge and
      improving patient care. The purpose of this article is to describe a
      methodological design for investigating how KTs come about in participatory
      research. METHODS AND ANALYSIS: The article presents an ethnographic study which
      investigates meetings between participants in a participatory research project.
      The participants are researchers and primary healthcare clinicians. Data are
      collected through observation, interviews and document studies. The material is
      analysed using the analytical concepts of knowledge objects, knowledge forms and
      knowledge positions. These concepts represent an analytical framework enabling us
      to observe knowledge and how it is translated between participants. The main
      expected outcome of our study is to develop a typology of KT practices relevant
      to participatory research. ETHICS AND DISSEMINATION: The project has been
      evaluated and approved by the Norwegian Social Science Data Services. Informed
      consent was obtained for all participants. The findings from this study will be
      disseminated through peer-reviewed publications and national and international
      conference presentations.

PMID- 23959759
TI  - Impact of helicopter emergency medical services in major incidents: systematic
      literature review.
AB  - INTRODUCTION: Helicopter emergency medical services (HEMS) aim to bring highly
      specialised crews to the major incident for triage, treatment and transport. When
      the site is difficult to access, HEMS may be the only mode of transportation of
      both personnel and patients. This systematic review will identify, describe and
      appraise literature regarding the role of HEMS in medical response to major
      incidents. We aim to improve knowledge on HEMS role in a major incident and
      provide a basis for future research. METHODS AND ANALYSIS: A systematic
      literature review will be conducted with search phrases that combine HEMS and
      major incidents to identify when and how HEMS have been used. Included literature
      will be subject to quality appraisal and data extraction. ETHICS: No ethical
      approval is sought because this is a literature review. It will be submitted to a
      peer-reviewed journal and the PRISMA guidelines will be followed. REGISTRATION
      DETAILS: PROSPERO CRD42013004473.

PMID- 23959760
TI  - Predicting risk of emergency admission to hospital using primary care data:
      derivation and validation of QAdmissions score.
AB  - OBJECTIVE: To develop and externally validate a risk algorithm (QAdmissions) to
      estimate the risk of emergency hospital admission for patients aged 18-100 years
      in primary care. DESIGN: Prospective open cohort study using routinely collected
      data from general practice linked to hospital episode data during the 2-year
      study period 1 January 2010 to 31 December 2011. SETTING: 405 general practices
      in England contributing to the national QResearch database to develop the
      algorithm. Two validation cohorts to validate the algorithm (1) 202 different
      QResearch practices and (2) 343 practices in England contributing to the Clinical
      Practice Research DataLink (CPRD). All general practices had data linked to
      hospital episode statistics at the individual patient level. PARTICIPANTS: We
      studied 2 849 381 patients aged 18-100 years in the derivation cohort with over
      4.6 million person-years of follow-up. 265 573 of these patients had one or more
      emergency admissions during follow-up. For the QResearch validation cohort, we
      identified 1 340 622 patients aged 18-100 years with over 2.2 million person
      years of follow-up. Of these patients, 132 723 had one or more emergency
      admissions during follow-up. The CPRD cohort included 2 475 360 patients aged 18
      100 years with over 3.8 million person-years of follow-up. 234 204 of these
      patients had one or more emergency admissions during follow-up. We excluded
      patients without a valid NHS number and a valid Townsend score. ENDPOINT: First
      (ie, incident) emergency admission to hospital in the next 2 years as recorded on
      the linked hospital episodes records. RISK FACTORS: Candidate variables recorded
      on the general practitioner computer system including (1) demographic variables
      (age, sex, strategic health authority, Townsend deprivation score, ethnicity);
      (2) lifestyle variables (smoking, alcohol intake); (3) chronic diseases; (4)
      prescribed medication; (5) clinical values (body mass index, systolic blood
      pressure); (6) laboratory test results (haemoglobin, platelets, erythrocyte
      sedimentation rate, ratio of total serum cholesterol to high density lipoprotein
      cholesterol concentrations, liver function tests). We also included the number of
      emergency admissions in the preceding year based on information recorded on the
      linked hospital episodes records. RESULTS: The final QAdmissions algorithm
      incorporated 30 variables. When applied to the QResearch validation cohort, it
      explained 41% of the variation in women and 43% of that in men. The D statistic
      for QAdmissions was 1.7 in women and 1.8 in men. The receiver operating curve
      statistic was 0.78 for men and 0.77 for women. QAdmissions had good performance
      on all measures of discrimination and calibration. The positive predictive value
      for emergency admissions for the top tenth of patients at highest risk was 42%
      and the sensitivity was 39%. The results for the CPRD validation cohort were
      similar. CONCLUSIONS: The QAdmissions model provided a valid measure of absolute
      risk of emergency admission to hospital in the general population as shown by its
      performance in a separate validation cohort. Further research is needed to
      evaluate the cost-effectiveness of using these algorithms in primary care.

PMID- 23959761
TI  - Design of an instrument to measure alcohol-related psychosocial influences in the
      development of norms among 13-year-old to 17-year-old adolescents.
AB  - INTRODUCTION: Harmful drinking among young people is common in Australia and many
      other countries. Social norms and their influence on adolescents' alcohol
      consumption behaviours have received much research attention in recent years.
      However, there is limited understanding of how social norms related to alcohol
      are developed and transmitted across social networks and a specific tool that
      measures these constructs has yet to be developed. This paper outlines the
      rationale and protocol for the design and validation of a multidimensional survey
      instrument which measures the development and transmission pathways of alcohol
      related norms among adolescents. A longer term aim is to apply the instrument in
      a respondent-driven sampling study with a large adolescent cohort. METHODS AND
      ANALYSIS: Social Cognitive Theory (SCT) and relevant literature will guide the
      design of the online survey instrument. Feedback from a practitioner-based
      stakeholder committee, academic expert panel reviews, focus groups and interviews
      with adolescents aged 13-17 years in Perth, Western Australia (WA) will serve to
      ascertain content and face validity. A test-retest will be conducted using a
      purposive sample of students (n=400) at secondary schools in Perth. The
      instrument's psychometric properties will be analysed, including exploratory
      factor analyses, discriminant validity, internal consistency and test-retest
      reliability. ETHICS AND DISSEMINATION: The results of this research will provide
      public health researchers and practitioners with a comprehensive standardised
      instrument to explore the characteristics of individual-level and community-level
      social influences and norms associated with use of alcohol by adolescents and the
      routes through which these norms are transmitted. The data collected by the
      instrument is anticipated to inform the design of youth specific interventions
      with the potential to reduce alcohol-related harms. The Study findings will be
      disseminated widely through peer-reviewed publications and conference
      presentations. The study has received approval from the Curtin University Human
      Research Ethics Committee.

PMID- 23959762
TI  - Lovastatin dose-dependently potentiates the pro-inflammatory activity of
      lipopolysaccharide both in vitro and in vivo.
AB  - Since contradictory findings have been reported on potential effects of statins
      in modulating the inflammatory response, we have analysed the biological activity
      of lovastatin both in vitro using the Raw 264.7 murine macrophagic cell line and
      in vivo using BALB/c mice. When added to Raw 264.7 cells in combination with
      lipopolysaccharide, lovastatin significantly potentiated the release of
      interleukin-1beta, interleukin-6 and interleukin-12 with respect to
      lipopolysaccharide alone and showed an additive effect on the release of nitric
      oxide. Similarly, when lovastatin was intraperitoneally administrated to BALB/c
      mice, it did not induce any pro-inflammatory effect when used alone, but it
      significantly potentiated the pro-inflammatory activity of lipopolysaccharide, in
      terms of number of intraperitoneal cells and serum levels of serum amyloid A,
      interleukin-1beta, interleukin-6 and interleukin-12. A potential clinical
      implication of our study is that lovastatin might exert a pro-inflammatory
      activity in subjects affected by inflammatory processes, with clinically evident
      or subclinical infections.

PMID- 23959763
TI  - Maternal positions and mobility during first stage labour.
AB  - BACKGROUND: It is more common for women in both high- and low-income countries
      giving birth in health facilities, to labour in bed. There is no evidence that
      this is associated with any advantage for women or babies, although it may be
      more convenient for staff. Observational studies have suggested that if women lie
      on their backs during labour this may have adverse effects on uterine
      contractions and impede progress in labour, and in some women reduce placental
      blood flow. OBJECTIVES: To assess the effects of encouraging women to assume
      different upright positions (including walking, sitting, standing and kneeling)
      versus recumbent positions (supine, semi-recumbent and lateral) for women in the
      first stage of labour on duration of labour, type of birth and other important
      outcomes for mothers and babies. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (31 January 2013). SELECTION
      CRITERIA: Randomised and quasi-randomised trials comparing women randomised to
      upright versus recumbent positions in the first stage of labour. DATA COLLECTION
      AND ANALYSIS: We used methods described in the Cochrane Handbook for Systematic
      Reviews of Interventions for carrying out data collection, assessing study
      quality and analysing results. Two review authors independently evaluated
      methodological quality and extracted data for each study. We sought additional
      information from trial authors as required. We used random-effects analysis for
      comparisons in which high heterogeneity was present. We reported results using
      the average risk ratio (RR) for categorical data and mean difference (MD) for
      continuous data. MAIN RESULTS: Results should be interpreted with caution as the
      methodological quality of the 25 included trials (5218 women) was variable.For
      Comparison 1: Upright and recumbent positions versus recumbent positions and bed
      care, the first stage of labour was approximately one hour and 22 minutes shorter
      for women randomised to upright as opposed to recumbent positions (average MD 
      1.36, 95% confidence interval (CI) -2.22 to -0.51; 15 studies, 2503 women; random
      effects, T(2) = 2.39, Chi(2) = 203.55, df = 14, (P < 0.00001), I(2) = 93%). Women
      who were upright were also less likely to have caesarean section (RR 0.71, 95% CI
      0.54 to 0.94; 14 studies, 2682 women) and less likely to have an epidural (RR
      0.81, 95% CI 0.66 to 0.99, nine studies, 2107 women; random-effects, T(2) = 0.02,
      I(2) = 61%). Babies of mothers who were upright were less likely to be admitted
      to the neonatal intensive care unit, however this was based on one trial (RR
      0.20, 95% CI 0.04 to 0.89, one study, 200 women). There were no significant
      differences between groups for other outcomes including duration of the second
      stage of labour, or other outcomes related to the well being of mothers and
      babies.For Comparison 2: Upright and recumbent positions versus recumbent
      positions and bed care (with epidural: all women), there were no significant
      differences between groups for outcomes including duration of the second stage of
      labour, or other outcomes related to the well being of mothers and babies.
      AUTHORS' CONCLUSIONS: There is clear and important evidence that walking and
      upright positions in the first stage of labour reduces the duration of labour,
      the risk of caesarean birth, the need for epidural, and does not seem to be
      associated with increased intervention or negative effects on mothers' and
      babies' well being. Given the great heterogeneity and high performance bias of
      study situations, better quality trials are still required to confirm with any
      confidence the true risks and benefits of upright and mobile positions compared
      with recumbent positions for all women. Based on the current findings, we
      recommend that women in low-risk labour should be informed of the benefits of
      upright positions, and encouraged and assisted to assume whatever positions they
      choose.

PMID- 23959765
TI  - Discovery and biological activity of new chondramides from Chondromyces sp.
AB  - Myxobacteria have proven to be highly valuable sources of natural products, as
      they produce a variety of secondary metabolites with unique structures and often
      new modes of action. In this study, high-content screening is demonstrated to be
      a convenient tool for bioactivity-guided isolation of natural products from crude
      bacterial extracts. By the application of focused, image-based screens we were
      able to identify over 30 novel chondramide derivatives from Chondromyces sp.
      MSr9030, some of which were present in only minute amounts. These cyclic
      depsipeptides were shown to target actin filaments with a similar binding mode to
      that of the mushroom toxin phalloidin. Fermentations of the myxobacterial strain
      were carried out under improved cultivation conditions, and supplementation of
      the culture broth with potassium bromide afforded the production of brominated
      analogues that are superior (in terms of biological activity) to all chondramides
      described to date. Initial biological profiling of 11 new derivatives in
      comparison to the reference compounds (chondramides A-C) showed that bromo
      chondramide C3 and propionyl-bromo-chondramide C3 are the most active in cell
      based studies, with GI50 values on human cancer cell lines in the low nanomolar
      range. Given that these brominated C3 analogues were also less potent on
      noncancerous human cells (by a factor of 2 to 4 in comparison to cancer cell
      lines), our results can aid further structure-activity relationship-guided
      development of chondramides, either as molecular probes or pharmaceutical agents.

PMID- 23959766
TI  - Extending JAGS: a tutorial on adding custom distributions to JAGS (with a
      diffusion model example).
AB  - We demonstrate how to add a custom distribution into the general-purpose, open
      source, cross-platform graphical modeling package JAGS ("Just Another Gibbs
      Sampler"). JAGS is intended to be modular and extensible, and modules written in
      the way laid out here can be loaded at runtime as needed and do not interfere
      with regular JAGS functionality when not loaded. Writing custom extensions
      requires knowledge of C++, but installing a new module can be highly automatic,
      depending on the operating system. As a basic example, we implement a Bernoulli
      distribution in JAGS. We further present our implementation of the Wiener
      diffusion first-passage time distribution, which is freely available at
      https://sourceforge.net/projects/jags-wiener/ . 

PMID- 23959764
TI  - Ovarian steroids increase PSD-95 expression and dendritic spines in the dorsal
      raphe of ovariectomized macaques.
AB  - Estradiol (E) and progesterone (P) promote spinogenesis in several brain areas.
      Intracellular signaling cascades that promote spinogenesis involve RhoGTPases,
      glutamate signaling and synapse assembly. We found that in serotonin neurons, E
      +/- P administration increases (a) gene and protein expression of RhoGTPases, (b)
      gene expression of glutamate receptors, and (c) gene expression of pivotal
      synapse assembly proteins. Therefore, in this study we determined whether
      structural changes in dendritic spines in the dorsal raphe follow the observed
      changes in gene and protein expression. Dendritic spines were examined with
      immunogold silver staining of a spine marker protein, postsynaptic density-95
      (PSD-95) and with Golgi staining. In the PSD-95 study, adult Ovx monkeys received
      placebo, E, P, or E + P for 1 month (n = 3/group). Sections were immunostained
      for PSD-95 and the number of PSD-95-positive puncta was determined with
      stereology. E, P, and E + P treatment significantly increased the total number of
      PSD-95-positive puncta (ANOVA, P = 0.04). In the golgi study, adult Ovx monkeys
      received placebo, E or E + P for 1 month (n = 3-4) and the midbrain was golgi
      stained. A total of 80 neurons were analyzed with Neurolucida software. There was
      a significant difference in spine density that depended on branch order (two-way
      ANOVA). E + P treatment significantly increased spine density in higher-order (3
      degrees -5 degrees ) dendritic branches relative to Ovx group (Bonferroni, P <
      0.05). In summary, E + P leads to the elaboration of dendritic spines on dorsal
      raphe neurons. The ability of E to induce PSD-95, but not actual spines, suggests
      either a sampling or time lag issue. Increased spinogenesis on serotonin
      dendrites would facilitate excitatory glutamatergic input and, in turn, increase
      serotonin neurotransmission throughout the brain.

PMID- 23959767
TI  - A well-defined Pd hybrid material for the Z-selective semihydrogenation of
      alkynes characterized at the molecular level by DNP SENS.
AB  - Direct evidence of the conformation of a Pd-N heterocyclic carbene (NHC) moiety
      imbedded in a hybrid material and of the Pd-NHC bond were obtained by dynamic
      nuclear polarization surface-enhanced NMR spectroscopy (DNP SENS) at natural
      abundance in short experimental times (hours). Overall, this silica-based hybrid
      material containing well-defined Pd-NHC sites in a uniform environment displays
      high activity and selectivity in the semihydrogenation of alkynes into Z-alkenes
      (see figure).

PMID- 23959768
TI  - Ovarian follicular morphometry of South American fur seal pups (Arctophoca
      australis).
AB  - The aim of this study was to analyze the morphometric characteristics of ovarian
      follicles and their distribution in the ovarian cortex in South American fur seal
      pups (Arctophoca australis). Samples were obtained from animals stranded in the
      Uruguayan Atlantic coast. Ovaries were dissected, fixed, weighed, and processed
      by standard histological techniques. Ovarian weight increased with pup age and
      body length. There was an increase in the diameter of the oocytes (22.24 +/- 0.6
      to 68.2 +/- 5.3 um), the nuclei (10.04 +/- 0.2 to 20.7 +/- 1.6 um), and follicles
      (30.4 +/- 1.2 to 252.6 +/- 53.6 um) of type 1 to type 5 follicles; there was a
      wide range of variation in the diameter of follicle type 4 and 5. Granulosa layer
      thickness increased between follicles type 3 and 4, whereas between type 4 and 5
      there was a reduction. Thecal layer from follicles type 3 and 4 consisted of 1-2
      layers of cells, whereas type 5 showed an increase in thickness (3.13 +/- 0.3 to
      13.8 +/- 5.2 um). Follicles type 1 and 2 occupied superficial regions within the
      ovarian cortex while the remaining follicles had a deeper location. These results
      provide a basis for comparison with females of other age categories as well as
      follicular dynamics studies in South American fur seals.

PMID- 23959770
TI  - Parent-child relationships in gender identity disorder.
AB  - OBJECTIVE: To describe the relationship between parents with gender identity
      disorder (GID) and their child(ren) as described by the parent and to understand
      how being a parent affects transitioning from one gender to the other. METHODS:
      Fourteen parents with GID underwent a semi-structured interview and completed the
      Index of Parental Attitudes (IPA). An IPA score of greater than 30 indicates
      parent-child relationship difficulties (range 0-100). The authors also conducted
      the SCID-I to establish other Axis I disorders. RESULTS: We assessed 12 male to
      female and two female to male parents with GID residing in Ireland. In total, 14
      GID parents had 28 children. Three children had no relationship with their GID
      parent. The other 25 children, as reported by the parent, had good relationships
      with their children. In addition, these 25 children average score IPA score was
      6.4 (range 0-25). Twelve GID parents (86 %) believed that being a parent had no
      effect on their desired level of transitioning, while two were influenced not to
      transition. Eleven GID parents (79 %) reported that being a parent had increased
      the time taken to commence transitioning, two have stopped transitioning
      altogether, while one cited no effect on time. CONCLUSION: Parents with GID
      report positive relationships or no relationship with their children and the IPA
      revealed no clinical problems. Being a parent can prolong transitioning time in
      people with GID and can affect overall achieved level of transitioning.

PMID- 23959771
TI  - Enhancing Hispanic participation in mental health clinical research: development
      of a Spanish-speaking depression research site.
AB  - BACKGROUND: Hispanics, particularly those with limited English proficiency, are
      underrepresented in psychiatric clinical research studies. We developed a
      bilingual and bicultural research clinic dedicated to the recruitment and
      treatment of Spanish-speaking subjects in the Predictors of Remission in
      Depression to Individual and Combined Treatments (PReDICT) study, a large
      clinical trial of treatment-naive subjects with major depressive disorder (MDD).
      METHODS: Demographic and clinical data derived from screening evaluations of the
      first 1,174 subjects presenting for participation were compared between the
      Spanish-speaking site (N = 275) and the primary English-speaking site (N = 899).
      Reasons for ineligibility (N = 888) for the PReDICT study were tallied for each
      site. RESULTS: Compared to English speakers, Spanish speakers had a lower level
      of education and were more likely to be female, uninsured, and have uncontrolled
      medical conditions. Clinically, Spanish speakers demonstrated greater depression
      severity, with higher mean symptom severity scores, and a greater number of
      previous suicide attempts. Among the subjects who were not randomized into the
      PReDICT study, Spanish-speaking subjects were more likely to have an uncontrolled
      medical condition or refuse participation, whereas English-speaking subjects were
      more likely to have bipolar disorder or a non-MDD depressive disorder.
      CONCLUSION: Recruitment of Hispanic subjects with MDD is feasible and may enhance
      efforts at signal detection, given the higher severity of depression among
      Spanish-speaking participants presenting for clinical trials. Specific approaches
      for the recruitment and retention of Spanish-speaking participants are required.

PMID- 23959772
TI  - Does rich coronary collateral circulation distal to chronically occluded left
      anterior descending artery compete with graft flow?
AB  - OBJECTIVES: In coronary artery bypass grafting (CABG), graft flow distal to a
      mild stenosis can compete with relatively preserved native flow through the
      stenosis and the competition can result in graft stenosis. In chronic total
      occlusion (CTO), coronary collateral circulation, which is essential to maintain
      myocardial viability distal to CTO, varies in extent among patients and the
      extent can be scored by Rentrop grade in coronary angiography. We investigated
      whether rich collateral circulation distal to CTO competes with distally
      anastomosed graft flow in association with Rentrop grade. METHODS: Of 666
      patients who underwent CABG from January 2001 to December 2012, 70 patients whose
      left internal thoracic artery (ITA) was grafted distal to CTO in the left
      anterior descending artery (LAD) were divided into three groups: Poor collaterals
      (Rentrop grades 0 and 1, Group P, n = 22), Moderate collaterals (grade 2, Group
      M, n = 23) and Rich collaterals (grade 3, Group R, n = 25). The intraoperative
      measurements of mean graft flow (MGF) and pulsatility index (PI) of left ITA
      grafts, early graft patency and long-term clinical outcomes were compared.
      RESULTS: The MGF and PI of left ITA grafts differed significantly among the three
      groups (P = 0.025 and P = 0.046, respectively). Lower Rentrop grade was
      associated with preferable results of higher MGF and lower PI. The graft flow
      pattern in Group P showed a significantly higher MGF (P = 0.020) and lower PI (P
      = 0.041) than those in Group R. All early postoperative coronary angiograms
      showed patent left ITA grafts. Serial echocardiographic evaluations, survival
      rates and cardiac event-free rates were comparable with the follow-up of 5.00 +/-
      3.11 years. CONCLUSIONS: Rich collateral circulation distal to CTO in LADs can
      potentially compete with graft flow, although the competition seems not to affect
      clinical outcomes probably due to the regression of collaterals surmounted by the
      graft flow. Rentrop grade is shown to certainly reflect the degree of collateral
      haemodynamic circulation distal to CTO and especially important to evaluate
      intraoperative graft flow appropriately, considering the possible phenomenon of
      graft flow competition.

PMID- 23959773
TI  - Phylogenetic position of Indian termites (Isoptera: Termitidae) with their
      respective genera inferred from DNA sequence analysis of the mitochondrial
      cytochrome oxidase gene subunit I compared to subunit II.
AB  - The present work was aimed to investigate the phylogenetic analysis of different
      species of Indian termites belonging to the family termitidae based on
      mitochondrial genes COI and COII. The sequences so obtained from public database
      revealed grouping of termites according to their ecological distribution. The
      sequences of the species under investigation were characterized on the basis of
      frequencies of nucleotide bases and in most of the species, a significantly high
      percentage of A+T base composition was observed. Phylogenetic tree revealed
      positioning of species according to the analysis of their cytochrome oxidase
      subunits.

PMID- 23959775
TI  - Characteristics of the Japanese histological classification for breast cancer:
      correlations with imaging and cytology.
AB  - The Japanese histological classification of breast cancer is a unique
      classification that was published as the 2nd edition of the General Rules for
      Clinical and Pathological Recording of Breast Cancer in 1971. According to this
      classification, breast cancers are divided into three subgroups: noninvasive,
      invasive, and Paget's disease. Invasive carcinomas are further divided into two
      groups: invasive ductal carcinomas (IDCs) and special types. IDCs are the most
      common types, representing 70-80 % of all breast cancers, and most of them
      correspond to invasive carcinoma-not special type-according to the latest WHO
      classification (4th edition). In particular, IDCs are subdivided into three
      subgroups as follows: (1) papillotubular carcinoma, which is characterized by the
      projection of papillae into spaces, and includes cribriform and comedo patterns;
      (2) solid-tubular carcinoma, which is a solid cluster of cancer cells with
      expansive growths that form relatively sharp borders; and (3) scirrhous
      carcinoma, which grows in a scirrhous manner characterized by cancer nests or
      cells accompanied by marked fibrosis. The concept of subclassification originated
      in Japan. The Japanese histological classification has taken on important roles
      since its publication, in particular for comparisons between histology and
      imaging or cytology.

PMID- 23959774
TI  - Malignant mesothelioma: development to therapy.
AB  - Malignant mesothelioma (MM) is an aggressive cancer of the mesothelium caused by
      asbestos. Asbestos use has been reduced but not completely stopped. In addition,
      natural or man-made disasters will continue to dislodge asbestos from old
      buildings into the atmosphere and as long as respirable asbestos is available, MM
      will continue to be a threat. Due to the long latency period of MM development,
      it would still take decades to eradicate this disease if asbestos was completely
      removed from our lives today. Therefore, there is a need for researchers and
      clinicians to work together to understand this deadly disease and find a solution
      for early diagnosis and treatment. This article focuses on developmental
      mechanisms as well as current therapies available for MM.

PMID- 23959776
TI  - Diagnostic performance of fluorine-18-fluorodeoxyglucose positron emission
      tomography in patients with Merkel cell carcinoma: a systematic review and meta
      analysis.
AB  - BACKGROUND: Some studies reported the usefulness of fluorine-18
      fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and PET/computed
      tomography (CT) in patients with Merkel cell carcinoma (MCC). OBJECTIVE: The aim
      of this study was to systematically review and meta-analyze published data about
      the diagnostic performance of 18F-FDG PET and PET/CT in patients with MCC.
      METHODS: A comprehensive literature search of studies published through June 2013
      regarding 18F-FDG PET and PET/CT in patients with MCC was performed. All
      retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity,
      specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic
      odds ratio (DOR) of 18F-FDG PET or PET/CT in patients with MCC on a per
      examination-based analysis were calculated. The area under the summary receiver
      operating characteristic (ROC) curve was calculated to measure the accuracy of
      18F-FDG PET or PET/CT in these patients. RESULTS: Ten studies comprising 329
      patients (549 scans) with MCC were included in the qualitative analysis
      (systematic review) and discussed. The quantitative analysis (meta-analysis) of
      six selected studies (including 92 patients with MCC) provided the following
      results on a per examination-based analysis: sensitivity was 90 % (95 % CI 80
      96), specificity 98 % (95 % CI 90-100), LR+ 12 (95 % CI 4.3-33.0), LR- 0.15 (95 %
      CI 0.08-0.28), and DOR 86.8 (95 % CI 23-327). The area under the summary ROC
      curve was 0.96. No significant statistical heterogeneity between the studies was
      found. CONCLUSIONS: In patients with MCC, 18F-FDG PET or PET/CT demonstrated high
      sensitivity and specificity, being accurate methods in this setting.
      Nevertheless, the literature focusing on the use of PET and PET/CT in MCC still
      remains limited. Prospective studies are needed to substantiate the high
      diagnostic accuracy of these methods in MCC.

PMID- 23959777
TI  - Variety and delicacy of animal mechanism.

PMID- 23959778
TI  - Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders
      (ASD).
AB  - BACKGROUND: Autism spectrum disorders (ASD) are characterised by abnormalities in
      social interaction and communication skills, as well as stereotypic behaviours
      and restricted activities and interests. Selective serotonin reuptake inhibitors
      (SSRIs) are prescribed for the treatment of conditions often comorbid with ASD
      such as depression, anxiety and obsessive-compulsive behaviours. OBJECTIVES: To
      determine if treatment with an SSRI:1. improves the core features of autism
      (social interaction, communication and behavioural problems);2. improves other
      non-core aspects of behaviour or function such as self-injurious behaviour;3.
      improves the quality of life of adults or children and their carers;4. has short-
      and long-term effects on outcome;5. causes harm. SEARCH METHODS: We searched the
      following databases up until March 2013: CENTRAL, Ovid MEDLINE, Embase, CINAHL,
      PsycINFO, ERIC and Sociological Abstracts. We also searched ClinicalTrials.gov
      and the International Clinical Trials Registry Platform (ICTRP). This was
      supplemented by searching reference lists and contacting known experts in the
      field. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any dose of
      oral SSRI compared with placebo, in people with ASD. DATA COLLECTION AND
      ANALYSIS: Two authors independently selected studies for inclusion, extracted
      data and appraised each study's risk of bias. MAIN RESULTS: Nine RCTs with a
      total of 320 participants were included. Four SSRIs were evaluated: fluoxetine
      (three studies), fluvoxamine (two studies), fenfluramine (two studies) and
      citalopram (two studies). Five studies included only children and four studies
      included only adults. Varying inclusion criteria were used with regard to
      diagnostic criteria and intelligence quotient of participants. Eighteen different
      outcome measures were reported. Although more than one study reported data for
      Clinical Global Impression (CGI) and obsessive-compulsive behaviour (OCB),
      different tool types or components of these outcomes were used in each study. As
      such, data were unsuitable for meta-analysis, except for one outcome (proportion
      improvement). One large, high-quality study in children showed no evidence of
      positive effect of citalopram. Three small studies in adults showed positive
      outcomes for CGI and OCB; one study showed improvements in aggression, and
      another in anxiety. AUTHORS' CONCLUSIONS: There is no evidence of effect of SSRIs
      in children and emerging evidence of harm. There is limited evidence of the
      effectiveness of SSRIs in adults from small studies in which risk of bias is
      unclear.

PMID- 23959779
TI  - TRAIL is involved in the tumoricidal activity of mouse natural killer cells
      stimulated by Newcastle disease virus in vitro.
AB  - Newcastle disease virus (NDV) is a potential antitumor agent, and its antitumor
      effect has been evaluated in preclinical tests. However, the mechanisms of NDV
      based antitumor therapy are still not completely clear. In the present study we
      found that NDV-stimulation enhanced the killing ability of mouse spleen natural
      killer (NK) cells towards mouse hepatoma cell lines, and tumor necrosis factor
      (TNF)-related apoptosis-inducing ligand (TRAIL) plays an important role in this
      tumoricidal activity. NDV stimulation induced up-regulation of TRAIL both at the
      mRNA and protein levels in NK cells. Blocking TRAIL by antibody (Ab) almost
      completely eliminated the killing effect of NK cells on hepatoma cell lines.
      Furthermore, neutralizing interferon (IFN)-gamma by Ab could inhibit TRAIL
      expression and tumoricidal activity of NDV-stimulated NK cells. These results
      indicated a substantial role of TRAIL as an effector molecule in NDV-induced NK
      cells mediated tumoricidal activity. The NDV stimulation triggered TRAIL
      expression in mouse spleen NK cells could be mediated by IFN-gamma induction.

PMID- 23959780
TI  - New approaches to modulating idiopathic pulmonary fibrosis.
AB  - Until recently, idiopathic pulmonary fibrosis (IPF) has been a devastating and
      generally fatal disease with no effective therapeutic. New developments in
      understanding the biology of the disease include a growing consensus that the
      lesions are mainly composed of cells that originated from resident fibroblasts.
      New developments in therapeutics include recommendations against several
      treatment regimes that have been previously used. On a positive note, the orally
      available drug pirfenidone has been approved for use in IPF in China, Japan,
      India, and the European Union, but not yet in the United States. Other
      possibilities for managing IPF include managing gastrointestinal reflux, and
      limiting excessive salt intake. A variety of potential therapeutics for IPF are
      in clinical trials; for instance, in a Phase 1b trial, intravenous injections of
      a recombinant version of the normal human serum protein Serum Amyloid P (SAP,
      also known as PTX2) improved lung function in IPF patients.

PMID- 23959781
TI  - Neuro-ventilatory efficiency during weaning from mechanical ventilation using
      neurally adjusted ventilatory assist.
AB  - BACKGROUND: Neuro-ventilatory efficiency (NVE), defined as the tidal volume to
      electrical diaphragm-activity ratio (VT/EAdi) at the beginning and end of the
      weaning process after acute hypoxaemic respiratory failure, may provide valuable
      information about patient recovery. METHODS: This observational study included 12
      patients breathing with neurally adjusted ventilatory assist (NAVA). When a
      spontaneous breathing trial (SBT) with pressure support of 7 cm H2O and PEEP was
      unsuccessful, NAVA was used and the level was adjusted to obtain an EAdi of ~60%
      of maximal EAdi during SBT. VT and EAdi were recorded continuously. We compared
      changes in NVE between NAVA and SBT at the first failed and first successful SBT.
      RESULTS: When patients were switched from NAVA to SBT, NVE was significantly
      reduced during both unsuccessful and successful SBT (-56 and -38%, respectively);
      however, this reduction was significantly lower when SBT was successful (P=0.01).
      Between the first and last day of weaning, we observed that NVE decreased with
      NAVA [40.6 (27.7-89.5) vs 28.8 (18.6-46.7); P=0.002] with a significant decrease
      in NAVA level, whereas it remained unchanged during SBT [15.4 (10.7-39.1) vs 19.5
      (11.6-29.6); P=0.50] with significant increases in both EAdi and VT and no
      difference in respiratory rhythm. CONCLUSIONS: These results suggest that in
      patients after respiratory failure and prolonged mechanical ventilation, changes
      in VT and NVE, between SBTs are indicative of patient recovery. Larger clinical
      trials are needed to clarify whether changes in NVE reliably predict weaning in
      patients ventilated with NAVA.

PMID- 23959782
TI  - Does adding milk to tea delay gastric emptying?
AB  - BACKGROUND: Many preoperative fasting guidelines suggest that hot tea or coffee
      with milk added should be considered similar to solid food, allowing an interval
      of 6 h before commencing anaesthesia. There is little evidence to support these
      instructions, with recent guidelines undecided on the issue. This study aimed to
      establish whether there was a clinically significant delay in gastric emptying
      associated with adding a modest amount of milk to tea. METHODS: This randomized
      controlled crossover study was conducted in 10 healthy volunteers. The
      paracetamol absorption technique and real-time ultrasound measurement of the
      cross-sectional area of the gastric antrum were used to assess gastric emptying
      after ingestion of 300 ml of black tea or 300 ml of tea with milk (250 ml black
      tea plus 50 ml of full fat milk). RESULTS: The mean difference in the time to
      reach the peak paracetamol concentration (tmax) was -8 min [95% confidence
      interval (CI) -23.1 to 7] in favour of tea with milk. Ultrasound assessment
      indicated that the geometric mean of the half-time to gastric emptying (T1/2)
      after tea without milk was 22.7 (95% CI 12.7-40.9) min and after tea with milk
      23.6 (95% CI 13.5-41.0) min (ratio 1.04) (95% CI 0.47-2.29). CONCLUSIONS: This
      study demonstrated no difference in gastric emptying times when a modest amount
      of milk was added to tea. These findings suggest that it may be acceptable to
      allow patients to add a small quantity of milk to their tea or coffee and follow
      the same fasting restrictions applied to clear fluids.

PMID- 23959783
TI  - Age-related changes of healthy bone marrow cell signaling in response to growth
      factors provide insight into low risk MDS.
AB  - Background Single Cell Network Profiling (SCNP) is a multiparametric flow
      cytometry-based assay that quantifiably and simultaneously measures changes in
      intracellular signaling proteins in response to in vitro extracellular modulators
      at the single cell level. Myelodysplastic syndrome (MDS) is a heterogeneous
      clonal disorder of hematopoietic stem cells that occurs in elderly subjects and
      is characterized by dysplasia and ineffective hematopoiesis. The functional
      responsiveness of MDS bone marrow (BM) hematopoietic cells, including
      functionally distinct myeloid and erythroid precursor subsets, to hematopoietic
      growth factors (HGF) and the relationship of modulated signaling to disease
      characteristics is poorly understood. Methods SCNP was used first to examine the
      effects of age on erythropoietin (EPO) and granulocyte colony stimulating factor
      (GCSF)-induced signaling in myeloid, nucleated red blood cells (nRBC), and CD34
      expressing cell subsets in healthy BM (n=15). SCNP was then used to map
      functional signaling profiles in low risk (LR) MDS (n=7) for comparison to
      signaling in samples from healthy donors and to probe signaling associations
      within clinically defined subgroups. Results In healthy BM samples, signaling
      responses to HGF were quite homogeneous (i.e. tightly regulated) with age
      dependent effects observed in response to EPO but not to GCSF. Despite the
      relatively small number of samples assayed in the study, LR MDS could be
      classified into distinct subgroups based on both cell subset frequency and
      signaling profiles. Conclusion As a correlate of underlying genetic
      abnormalities, signal transduction analyses may provide a functional and
      potentially clinically relevant classification of MDS. Further evaluation in a
      larger cohort is warranted. (c) 2013 Clinical Cytometry Society.

PMID- 23959784
TI  - Incorporation of nucleoside probes opposite O6-methylguanine by Sulfolobus
      solfataricus DNA polymerase Dpo4: importance of hydrogen bonding.
AB  - O6-Methylguanine (O6-MeG) is a mutagenic DNA lesion, arising from the action of
      methylating agents on guanine (G) in DNA. Dpo4, an archaeal low-fidelity Y-family
      DNA polymerase involved in translesion DNA synthesis (TLS), is a model for
      studying how human Y-family polymerases bypass DNA adducts. Previous work showed
      that Dpo4-mediated dTTP incorporation is favored opposite O6-MeG rather than
      opposite G. However, factors influencing the preference of Dpo4 to incorporate
      dTTP opposite O6-MeG are not fully defined. In this study, we investigated the
      influence of structural features of incoming dNTPs on their enzymatic
      incorporation opposite O6-MeG in a DNA template. To this end, we utilized a new
      fluorescence-based primer extension assay to evaluate the incorporation
      efficiency of a panel of synthetic dNTPs opposite G or O6-MeG by Dpo4. In single
      dNTP primer extension studies, the synthetic dNTPs were preferentially
      incorporated opposite G, relative to O6-MeG. Moreover, pyrimidine-based dNTPs
      were generally better incorporated than purine-based syn-conformation dNTPs. The
      results suggest that hydrophobicity of the incoming dNTP appears to have little
      influence on the process of nucleotide selection by Dpo4, with hydrogen bonding
      capacity being a major influence. Additionally, modifications at the C2-position
      of dCTP increase the selectivity for incorporation opposite O6-MeG without a
      significant loss of efficiency.

PMID- 23959785
TI  - Suboptimal effect of different vitamin D3 supplementations and doses adapted to
      baseline serum 25(OH)D on achieved 25(OH)D levels in patients with a recent
      fracture: a prospective observational study.
AB  - OBJECTIVE: Guidelines on the need for dose adaptation of vitamin D3
      supplementation according to baseline serum 25(OH)D are inconclusive. The effects
      of increasing doses of vitamin D3 at lower baseline serum 25(OH)D values on the
      serum 25(OH)D after 4.2 and 11 months were determined in an observational study.
      DESIGN: A prospective observational study. METHODS: Out of 1481 consecutive women
      and men with a recent clinical fracture, 707 had a baseline 25(OH)D level <50
      nmol/l and were supplemented with increasing doses of vitamin D3 (400, 800, 1700,
      and >=3500 IU/day) according to the lower baseline 25(OH)D. Final analysis was
      restricted to the 221 participants who had full follow-up data available for 11
      months. RESULTS: Serum 25(OH)D >=50 nmol/l was achieved in 57-76% of patients
      after 4.2 months and in 73-79% after 11 months. These percentages were similar
      for all doses (P=0.06 and P=0.91 respectively). The mean achieved 25(OH)D was
      similar for all dose groups (56.1-64.0 nmol/l after 4.2 months and 60.2-76.3
      nmol/l after 11 months). With multivariate analysis, the increase in 25(OH)D
      (17+/-32.0 after 4.2 months and 24.3+/-34.0 nmol/l after 11 months) was dependent
      on the baseline 25(OH)D (P<0.001), not on supplementation dose, season, age, BMI,
      or gender. CONCLUSIONS: The increase in serum 25(OH)D was significantly larger
      with higher vitamin D3 supplementation doses. However, this dose-effect response
      was mainly explained by the baseline 25(OH)D, not the supplementation dose, with
      a greater magnitude of response at lower baseline 25(OH)D concentrations. In 21
      27% of patients, serum 25(OH)D3 levels did not reach 50 nmol/l after 11 months,
      at any dose. Further studies are needed to identify possible causes of suboptimal
      response such as non-compliance, undiagnosed malabsorption syndromes, or
      variability in cholecalciferol content of the vitamin D supplements.

PMID- 23959786
TI  - Pre-pregnancy overweight overtakes gestational diabetes as a risk factor for
      subsequent metabolic syndrome.
AB  - OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with an increased
      risk of subsequent diabetes and metabolic syndrome (MS). The independent
      significance of overweight, often associated with GDM, is controversial. This
      study was aimed to investigate the prevalence of MS and carotid intima-media
      thickness (CIMT) values in normal and overweight women with previous insulin
      treated GDM and control without GDM 19 years after the index pregnancy. METHODS:
      The study group consisted of 61 women with prior GDM and 55 controls who gave
      birth in Oulu University Hospital between 1988 and 1993. These women were further
      divided into subgroups according to pre-pregnancy BMI (<25 or >=25 kg/m(2)). In
      2008-2010, anthropometrics and blood pressure were measured, blood samples were
      taken, and an oral glucose tolerance test was performed to investigate the
      components of MS. CIMT was measured by Doppler ultrasound. RESULTS: Total
      prevalence of MS was 62% in the GDM group and 31% in the control group (P=0.001);
      it was highest (86%) in GDM women with pre-pregnancy overweight. CIMT was
      significantly thicker (0.67 vs 0.56 mm, P=0.007) and more often abnormal (71.7 vs
      45.3%, P=0.004) in the GDM group compared with the controls. In logistic
      regression analysis, the strongest factor predicting MS in the whole study
      population was pre-pregnancy overweight. CONCLUSIONS: Pre-pregnancy overweight
      was the strongest predictive factor for later MS, whereas GDM indicated increased
      risk of subsequent diabetes and subclinical atherosclerosis. The risk of MS was
      highest when both of these factors were present.

PMID- 23959788
TI  - Postdeployment threat-related attention bias interacts with combat exposure to
      account for PTSD and anxiety symptoms in soldiers.
AB  - BACKGROUND: Recent studies suggest that assessment of threat-related attention
      bias may be useful in identifying soldiers at risk for clinical symptoms. The
      present study assessed the degree to which soldiers experienced combat events and
      showed attentional threat avoidance affected their reported levels of post
      traumatic stress disorder (PTSD) and anxiety symptoms. METHODS: Four months after
      a combat deployment to Iraq, 63 US soldiers completed a survey assessing combat
      exposures and clinical symptoms as well as a dot-probe task assessing threat
      related attention bias. RESULTS: Significant three-way interactions regressing
      threat reaction times (RTs), neutral RTs, and combat exposure on PTSD and anxiety
      symptoms were observed. Specifically, soldiers with high levels of combat
      exposure, who were more likely to demonstrate attentional bias away from threat,
      were also more symptomatic. CONCLUSION: These results demonstrate the potential
      of threat-related attention bias as a behavioral marker of PTSD and anxiety
      symptoms in a high-risk military occupational context.

PMID- 23959787
TI  - Cytomegalovirus DNAemia detected with real-time polymerase chain reaction in
      hematopoietic stem cell transplant patients.
AB  - INTRODUCTION: Cytomegalovirus (CMV) infections continue to cause significant
      morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients.
      Successful pre-emptive therapy in transplant patients depends on the availability
      of reliable diagnostic tests for CMV infections. The purpose of this
      retrospective study was to evaluate CMV DNA viral load, incidence of CMV disease
      and CMV seropositivity, risk factors and correlation between CMV DNA positivity
      and clinical course in HSCT patients. METHODS: Two hundred and twenty-five
      patients who underwent peripheral blood stem cell or bone marrow transplantation
      between June 2003 and April 2010 were included. A real-time polymerase chain
      reaction (RT-PCR) assay was used for CMV monitoring. RESULTS: Recipient median
      age was 42.5 years. CMV seropositivity was 95.6%. CMV DNA positivity determined
      by RT-PCR was 24.9% among the entire patient group. CMV DNA positivity with RT
      PCR was found to be significantly higher in allogeneic transplant recipients than
      autologous transplant recipients (46.7% vs 14.0%; P < 0.0001). Gender, age,
      conditioning regimen, stem cell source, underlying disease and recipient and
      donor seropositivity (alone or paired) were not significant risk factors for CMV
      DNAemia. We did not observe any CMV end-organ disease. CONCLUSION: CMV DNAemia
      was significantly higher in allogeneic transplant recipients than in autologous
      transplant patients. End-organ disease could be prevented with appropriate pre
      emptive therapy.

PMID- 23959789
TI  - 3,4-dihydroxybenzalacetone protects against Parkinson's disease-related
      neurotoxin 6-OHDA through Akt/Nrf2/glutathione pathway.
AB  - Oxidative stress is implicated in the pathogenesis of various neurodegenerative
      diseases including Parkinson's disease (PD). 3,4-Dihydroxybenzalacetone (DBL) is
      a small catechol-containing compound isolated from Chaga (Inonotus obliquus
      [persoon] Pilat), and has been reported to have beneficial bioactivities,
      including antioxidative, anti-inflammatory, and anti-tumorigenic activities, with
      a relatively low toxicity to normal cells. We, therefore, investigated the
      neuroprotective activity of DBL against the PD-related neurotoxin 6
      hydroxydopamine (6-OHDA). Pretreatment of human neuroblastoma SH-SY5Y cells with
      DBL, but not with another Chaga-derived catechol-containing compound, caffeic
      acid, dose-dependently improved the survival of 6-OHDA-treated cells. Although
      DBL did not reduce 6-OHDA-induced reactive oxygen species in the cell-free
      system, it promoted the translocation of Nrf2 to the nucleus, activated the
      transcription of Nrf2-dependent antioxidative genes, and increased glutathione
      synthesis in the cells. Buthionine sulfoximine, an inhibitor of glutathione
      synthesis, but not Sn-mesoporphyrin IX, a heme oxygenase-1 inhibitor, or
      dicoumarol, an NAD(P)H: quinone oxidoreductase 1 inhibitor, abolished the
      protective effect of DBL against 6-OHDA. Furthermore, DBL activated stress
      associated kinases such as Akt, ERK, and p38 MAPK, and PI3K or Akt inhibitors,
      but not ERK, p38, or JNK inhibitors, diminished DBL-induced glutathione synthesis
      and protection against 6-OHDA. These results suggest that DBL activates the
      Nrf2/glutathione pathway through PI3K/Akt, and improves survival of SH-SY5Y cells
      against 6-OHDA toxicity.

PMID- 23959790
TI  - Peer assessment among first year medical students in anatomy.
AB  - Peer assessment has been shown to be an effective tool to promote professionalism
      in medical students. Peer assessment may be particularly useful in anatomy
      dissection laboratory as the required close collaboration and long hours of
      anatomy laboratory provide students insights into their peers' work habits and
      interpersonal skills. The objective of this study was to quantitatively and
      qualitatively analyze the use of a validated peer assessment tool in Gross
      Anatomy. Students in a first year medical school class evaluated three members of
      their dissection group using an online survey tool. The mid-course and end-of
      course evaluation included open-ended comments, as well as a five-point scale
      that measured three work habits, two interpersonal attributes and one overall
      score. All 267 students completed the assignment. The overall score and four of
      the five other assessed categories showed significant improvement from the mid-
      to end-of-course evaluations. Quantitative and qualitative data also revealed
      significant improvement among the students who received the lowest mid-course
      assessments. Seventy-six percent of the class agreed with the statement: "Based
      on the feedback I received, I made a change in how I worked with or taught my
      peers." The use of this peer assessment tool used by students in anatomy was
      associated with improvements in work habits and interpersonal attributes,
      particularly by the cohort of students who received the lowest mid-course
      feedback. Peer assessment offers students an opportunity to improve their
      interpersonal skills and work habits.

PMID- 23959791
TI  - Anatomy and biomechanics of gluteus maximus and the thoracolumbar fascia at the
      sacroiliac joint.
AB  - Biomechanical models predict that recruitment of gluteus maximus (GMax) will
      exert a compressive force across the sacroiliac joint (SIJ), yet this muscle
      requires morphologic assessment. The aims of this study were to document GMax's
      proximal attachments and assess their capacity to generate forces including
      compressive force at the SIJ. In 11 embalmed cadaver limbs, attachments of GMax
      crossing the SIJ were dissected and their fascicle orientation, length and
      attachment volume documented. The physiological cross-sectional area (PCSA) of
      each attachment was calculated along with its estimated maximum force at the SIJ
      and lumbar spine. GMax fascicles originated from the gluteus medius fascia,
      ilium, thoracolumbar fascia, erector spinae aponeurosis, sacrum, coccyx, dorsal
      sacroiliac and sacrotuberous ligaments in all specimens. Their mean fascicle
      orientation ranged from 32 to 45 degrees  below horizontal and mean length from
      11 to 18 cm. The mean total PCSA of GMax was 26 cm(2) (range 16-36), of which 70%
      crossed the SIJ. The average maximum force predicted to be generated by GMax's
      total attachments crossing each SIJ was 891 N (range 572-1,215), of which 70%
      (702 N: range 450-1,009) could act perpendicular to the plane of the SIJ. The
      capacity of GMax to generate an extensor moment at lower lumbar segments was
      estimated at 4 Nm (range 2-9.5). GMax may generate compressive forces at the SIJ
      through its bony and fibrous attachments. These may assist effective load
      transfer between lower limbs and trunk.

PMID- 23959792
TI  - Diabetic uremic syndrome studied with cerebral MR spectroscopy and CT perfusion.
AB  - Diabetic uremic syndrome (DUS) is an increasingly reported acute neurometabolic
      cerebral disease with characteristic clinical and imaging features. Clinical
      spectrum includes a wide range of movement disorders such as acute parkinsonism.
      Imaging studies show reversible (with hemodialysis) bilateral lesions in the
      lenticular nuclei. DUS pathophysiology has not been entirely clarified yet. Our
      case study shows certainly that LN lesions are characterized with increased
      lactate peak with MR spectroscopy and decreased perfusion in computerized
      tomography perfusion along with increased diffusion with apparent diffusion
      coefficient (ADC) mapping in the subacute phase of the syndrome. Abnormalities
      were almost normalized quickly after metabolic control by hemodialysis. Together
      with reports indicating that a deficit of glucose use exacerbated with acute
      increase of uremic toxins in bilateral LN, observed changes (lactate peak and
      hypoperfusion) led us to state that a primary metabolic depression may cause this
      syndrome. Metabolic depression is probably due to uncompensated uremic toxin
      accumulation related mitochondrial supression and/or dysfunction. This definition
      fits well to the other elements of DUS such as ADC evolution and marked lesion
      regression. Our single case study is not supportive of other previously credited
      mechanisms such as microvascular dysfunction related focal ischemia or
      hypoperfusion, prolonged uremic toxin related histotoxic hypoxia, central pontine
      myelinolysis-like demyelination and posterior leukoencephalopathy spectrum
      disorder related vasogenic edema.

PMID- 23959793
TI  - Screening, prevention, and ambitious management of diabetic macular edema in
      patients with type 1 diabetes.
AB  - Diabetic macular edema results from progressive retinopathy related to chronic
      hyperglycemic and inflammatory vascular damage. Loss of vision secondary to
      diabetic macular edema is the most common cause of vision loss in patients with
      diabetes. Blood glucose control remains the main means of preventing progression
      of retinopathy and macular edema. Recent advancements allowing more efficient
      mechanisms for screening patients and emerging treatments for macular edema have
      led to improved visual outcomes in this group of patients.

PMID- 23959795
TI  - Treg vaccination in autoimmune type 1 diabetes.
AB  - Foxp3+ regulatory T (Treg) cells are critical contributors to the establishment
      and maintenance of immunological self-tolerance. Autoimmune type 1 diabetes (T1D)
      is characterized by the loss of self-tolerance to the insulin-producing beta
      cells in the pancreas and the destruction of beta cells, resulting in the
      development of chronic hyperglycemia at diagnosis. The application of strong
      agonistic T-cell receptor ligands provided under subimmunogenic conditions
      functions as a critical means for the efficient de novo conversion of naive CD4+
      T cells into Foxp3+ Treg cells. The specific induction of Treg cells upon supply
      of strong-agonistic variants of certain self-antigens could therefore function as
      a critical instrument in order to achieve safe and specific prevention of
      autoimmunity such as T1D via the restoration of self-tolerance. Such
      immunotherapeutic strategies are being developed, and in the case of T1D aim to
      restrict autoimmunity and beta-cell destruction. In this review, we discuss the
      requirements and opportunities for Treg-based tolerance approaches with the goal
      of interfering with autoimmune T1D.

PMID- 23959794
TI  - Bioengineered sites for islet cell transplantation.
AB  - Although islet transplantation has demonstrated its potential use in treating
      type 1 diabetes, this remains limited by the need for daily immunosuppression.
      Islet encapsulation was then proposed with a view to avoiding any
      immunosuppressive regimen and related side effects. In order to obtain a standard
      clinical procedure in terms of safety and reproducibility, two important factors
      have to be taken into account: the encapsulation design (which determines the
      graft volume) and the implantation site. Indeed, the implantation site should
      meet certain requirements: (1) its space must be large enough for the volume of
      transplanted tissues; (2) there must be proximity to abundant vascularization
      with a good oxygen supply; (3) there must be real-time access to physiologically
      representative blood glucose levels; (4) there must be easy access for
      implantation and the reversibility of the procedure (for safety); and finally,
      (5) the site should have minimal early inflammatory reaction and promote long
      term survival. The aim of this article is to review possible preclinical/clinical
      implantation sites (in comparison with free islets) for encapsulated islet
      transplantation as a function of the encapsulation design: macro/microcapsules
      and conformal coating.

PMID- 23959796
TI  - Recent advances on host plants and expression cassettes' structure and function
      in plant molecular pharming.
AB  - Plant molecular pharming is a promising system to produce important recombinant
      proteins such as therapeutic antibodies, pharmaceuticals, enzymes, growth
      factors, and vaccines. The system provides an interesting alternative method to
      the direct extraction of proteins from inappropriate source material while
      offering the possibility to overcome problems related to product safety and
      source availability. Multiple factors including plant hosts, genes of interest,
      expression vector cassettes, and extraction and purification techniques play
      important roles in the plant molecular pharming. Plant species, as a biosynthesis
      platform, are a crucial factor in achieving high yields of recombinant protein in
      plant. The choice of recombinant gene and its expression strategy is also of
      great importance in ensuring a high amount of the recombinant proteins. Many
      studies have been conducted to improve expression, accumulation, and purification
      of the recombinant protein from molecular pharming systems. Re-engineered vectors
      and expression cassettes are also pivotal tools in enhancing gene expression at
      the transcription and translation level, and increasing protein accumulation,
      stability, retention and targeting of specific organelles. In this review, we
      report recent advances and strategies of plant molecular pharming while focusing
      on the choice of plant hosts and the role of some molecular pharming elements and
      approaches: promoters, codon optimization, signal sequences, and peptides used
      for upstream design, purification and downstream processing.

PMID- 23959797
TI  - Dynamic, electrostatic model for the generation and control of high-energy
      radical intermediates by a coenzyme B12-dependent enzyme.

PMID- 23959798
TI  - The yeast copper response is regulated by DNA damage.
AB  - Copper is an essential but potentially toxic redox-active metal, so the levels
      and distribution of this metal are carefully regulated to ensure that it binds to
      the correct proteins. Previous studies of copper-dependent transcription in the
      yeast Saccharomyces cerevisiae have focused on the response of genes to changes
      in the exogenous levels of copper. We now report that yeast copper genes are
      regulated in response to the DNA-damaging agents methyl methanesulfonate (MMS)
      and hydroxyurea by a mechanism(s) that requires the copper-responsive
      transcription factors Mac1 and AceI, copper superoxide dismutase (Sod1) activity,
      and the Rad53 checkpoint kinase. Furthermore, in copper-starved yeast, the
      response of the Rad53 pathway to MMS is compromised due to a loss of Sod1
      activity, consistent with the model that yeast imports copper to ensure Sod1
      activity and Rad53 signaling. Crucially, the Mac1 transcription factor undergoes
      changes in its redox state in response to changing levels of copper or MMS. This
      study has therefore identified a novel regulatory relationship between cellular
      redox, copper homeostasis, and the DNA damage response in yeast. 

PMID- 23959799
TI  - Smurf1-mediated Lys29-linked nonproteolytic polyubiquitination of axin negatively
      regulates Wnt/beta-catenin signaling.
AB  - Ubiquitination plays important and diverse roles in modulating protein functions.
      As a C2-WW-HECT-type ubiquitin ligase, Smad ubiquitination regulatory factor 1
      (Smurf1) commonly serves to regulate ubiquitin-dependent protein degradation in a
      number of signaling pathways. Here, we report a novel function of Smurf1 in
      regulating Wnt/beta-catenin signaling through targeting axin for nonproteolytic
      ubiquitination. Our data unambiguously demonstrate that Smurf1 ubiquitinates axin
      through Lys 29 (K29)-linked polyubiquitin chains. Unexpectedly, Smurf1-mediated
      axin ubiquitination does not lead to its degradation but instead disrupts its
      interaction with the Wnt coreceptors LRP5/6, which subsequently attenuates Wnt
      stimulated LRP6 phosphorylation and represses Wnt/beta-catenin signaling. The
      inhibitory function of Smurf1 on Wnt/beta-catenin signaling is further evidenced
      by analysis with Smurf1 knockout murine embryonic fibroblasts. We next identified
      K789 and K821 in axin as the ubiquitination sites by Smurf1. Consistently, Smurf1
      could neither disrupt the interaction of an axin(K789/821R) double mutant with
      LRP5/6 nor attenuate the phosphorylation of LRP6 in axin(K789/821R)-expressing
      cells. Collectively, our studies uncover Smurf1 as a new regulator for the
      Wnt/beta-catenin signaling pathway via modulating the activity of axin. 

PMID- 23959800
TI  - The role of Djp1 in import of the mitochondrial protein Mim1 demonstrates
      specificity between a cochaperone and its substrate protein.
AB  - A special group of mitochondrial outer membrane proteins spans the membrane once,
      exposing soluble domains to both sides of the membrane. These proteins are
      synthesized in the cytosol and then inserted into the membrane by an unknown
      mechanism. To identify proteins that are involved in the biogenesis of the single
      span model protein Mim1, we performed a high-throughput screen in yeast. Two
      interesting candidates were the cytosolic cochaperone Djp1 and the mitochondrial
      import receptor Tom70. Our results indeed demonstrate a direct interaction of
      newly synthesized Mim1 molecules with Tom70. We further observed lower steady
      state levels of Mim1 in mitochondria from djp1Delta and tom70 tom71Delta cells
      and massive mislocalization of overexpressed GFP-Mim1 to the endoplasmic
      reticulum in the absence of Djp1. Importantly, these phenotypes were observed
      specifically for the deletion of DJP1 and were not detected in mutant cells
      lacking any of the other cytosolic cochaperones of the Hsp40 family. Furthermore,
      the djp1Delta tom70Delta tom71Delta triple deletion resulted in a severe
      synthetic sick/lethal growth phenotype. Taking our results together, we
      identified Tom70 and Djp1 as crucial players in the biogenesis of Mim1. Moreover,
      the involvement of Djp1 provides a unique case of specificity between a
      cochaperone and its substrate protein. 

PMID- 23959801
TI  - A mortalin/HSPA9-mediated switch in tumor-suppressive signaling of
      Raf/MEK/extracellular signal-regulated kinase.
AB  - Dysregulated Raf/MEK/extracellular signal-regulated kinase (ERK) signaling, a
      common hallmark of tumorigenesis, can trigger innate tumor-suppressive
      mechanisms, which must be inactivated for carcinogenesis to occur. This innate
      tumor-suppressive signaling may provide a potential therapeutic target. Here we
      report that mortalin (HSPA9/GRP75/PBP74) is a novel negative regulator of
      Raf/MEK/ERK and may provide a target for the reactivation of tumor-suppressive
      signaling of the pathway in cancer. We found that mortalin is present in the
      MEK1/MEK2 proteome and is upregulated in human melanoma biopsy specimens. In
      different MEK/ERK-activated cancer cell lines, mortalin depletion induced cell
      death and growth arrest, which was accompanied by increased p21(CIP1)
      transcription and MEK/ERK activity. Remarkably, MEK/ERK activity was necessary
      for mortalin depletion to induce p21(CIP1) expression in B-Raf(V600E)-transformed
      cancer cells regardless of their p53 status. In contrast, in cell types
      exhibiting normal MEK/ERK status, mortalin overexpression suppressed B-Raf(V600E)
      or DeltaRaf-1:ER-induced MEK/ERK activation, p21(CIP1) expression, and cell
      cycle arrest. Other HSP70 family chaperones could not effectively replace
      mortalin for p21(CIP1) regulation, suggesting a unique role for mortalin. These
      findings reveal a novel mechanism underlying p21(CIP1) regulation in MEK/ERK
      activated cancer and identify mortalin as a molecular switch that mediates the
      tumor-suppressive versus oncogenic result of dysregulated Raf/MEK/ERK signaling.
      Our study also demonstrates that p21(CIP1) has dual effects under mortalin
      depleted conditions, i.e., mediating cell cycle arrest while limiting cell death.

PMID- 23959802
TI  - Retinol-binding protein 4 and its membrane receptor STRA6 control adipogenesis by
      regulating cellular retinoid homeostasis and retinoic acid receptor alpha
      activity.
AB  - Retinoids are vitamin A (retinol) derivatives and complex regulators of
      adipogenesis by activating specific nuclear receptors, including the retinoic
      acid receptor (RAR) and retinoid X receptor (RXR). Circulating retinol-binding
      protein 4 (RBP4) and its membrane receptor STRA6 coordinate cellular retinol
      uptake. It is unknown whether retinol levels and the activity of RAR and RXR in
      adipocyte precursors are linked via RBP4/STRA6. Here, we show that STRA6 is
      expressed in precursor cells and, dictated by the apo- and holo-RBP4 isoforms,
      mediates bidirectional retinol transport that controls RARalpha activity and
      subsequent adipocyte differentiation. Mobilization of retinoid stores in mice by
      inducing RBP4 secretion from the liver activated RARalpha signaling in the
      precursor cell containing the stromal-vascular fraction of adipose tissue.
      Retinol-loaded holo-RBP4 blocked adipocyte differentiation of cultured precursors
      by activating RARalpha. Remarkably, retinol-free apo-RBP4 triggered retinol
      efflux that reduced cellular retinoids, RARalpha activity, and target gene
      expression and enhanced adipogenesis synergistically with ectopic STRA6. Thus,
      STRA6 in adipocyte precursor cells links nuclear RARalpha activity to the
      circulating RBP4 isoforms, whose ratio in obese mice was shifted toward limiting
      the adipogenic potential of their precursors. This novel cross talk identifies a
      retinol-dependent metabolic function of RBP4 that may have important implications
      for the treatment of obesity. 

PMID- 23959804
TI  - Conducting polymer nanowire arrays for high performance supercapacitors.
AB  - This Review provides a brief summary of the most recent research developments in
      the fabrication and application of one-dimensional ordered conducting polymers
      nanostructure (especially nanowire arrays) and their composites as electrodes for
      supercapacitors. By controlling the nucleation and growth process of
      polymerization, aligned conducting polymer nanowire arrays and their composites
      with nano-carbon materials can be prepared by employing in situ chemical
      polymerization or electrochemical polymerization without a template. This kind of
      nanostructure (such as polypyrrole and polyaniline nanowire arrays) possesses
      high capacitance, superior rate capability ascribed to large electrochemical
      surface, and an optimal ion diffusion path in the ordered nanowire structure,
      which is proved to be an ideal electrode material for high performance
      supercapacitors. Furthermore, flexible, micro-scale, threadlike, and
      multifunctional supercapacitors are introduced based on conducting polyaniline
      nanowire arrays and their composites. These prototypes of supercapacitors utilize
      the high flexibility, good processability, and large capacitance of conducting
      polymers, which efficiently extend the usage of supercapacitors in various
      situations, and even for a complicated integration system of different electronic
      devices. 

PMID- 23959803
TI  - Restructuring the vocal fold lamina propria with endoscopic microdissection.
AB  - OBJECTIVES/HYPOTHESIS: The purposes of this preclinical study were to investigate
      histologic and rheologic outcomes of Microendoscopy of Reinke's space (MERS)
      guided minithyrotomy and to assess its instrumentation. STUDY DESIGN: Human
      cadaveric and in vivo animal study. METHODS: Three human cadaveric larynges were
      treated with MERS-guided placement of Radiesse VoiceGel and immediately evaluated
      histologically for biomaterial location. In the second part of this
      investigation, two scarred porcine larynges were treated with MERS-guided
      placement of HyStem-VF and rheologically evaluated 6 weeks later. Student t tests
      determined differences in viscoelastic properties of treated/untreated vocal
      folds. Sialendoscopes and microendoscopes were subjectively compared for their
      visualization capacity. RESULTS: MERS imaged the subepithelial area and vocal
      ligament, guiding both tissue dissection and biomaterial positioning.
      Sialendoscopes provided adequate visualization and feature incorporated working
      channels. Enhanced image clarity was created in a gas-filled rather than saline
      filled environment, per rater judgment. Histological analysis revealed desirable
      biomaterial positioning with MERS. Per rheological analysis, viscoelastic
      properties of the MERS-treated porcine vocal folds compared to uninjured vocal
      folds 6 weeks following treatment did not statistically differ. CONCLUSIONS: MERS
      guided laryngoplasty using sialendoscopes yielded satisfactory biomaterial
      positioning in the short-term and normalized rheologic tissue properties in the
      long-term, contributing to proof of concept for MERS in the treatment of
      scarring. Strengths of MERS include direct, real-time visualization of Reinke's
      space and an ability to manipulate surgical instruments parallel to the vocal
      fold edge while maintaining an intact epithelium. Future work will explore the
      clinical utility of MERS for addressing scarring, sulcus vocalis, and other
      intracordal processes.

PMID- 23959805
TI  - Pyrethroid poisoning: features and predictors of atypical presentations.
AB  - BACKGROUND: Although pyrethroids are known for low toxicity to humans, clinical
      systemic characteristics of pyrethroid poisoning remain undefined. We
      investigated atypical presentations of pyrethroid poisoning and the predictors,
      among those readily assessed in the emergency department. METHODS: 59 pyrethroid
      poisoning cases that were diagnosed and treated at the emergency department of
      Wonju Severance Christian Hospital from September 2004 to December 2012 were
      retrospectively reviewed. RESULTS: Atypical presentations were seen in 22
      patients (39.3%). Atypical presentations after pyrethroid poisoning included
      respiratory failure requiring ventilator care (10 patients, 17.9%), hypotension
      (systolic blood pressure <90 mm Hg) (6 patients, 10.7%), pneumonia (4 patients,
      7.1%), acute kidney injury (6 patients, 10.7%), Glasgow Coma Scale (GCS) <15 (19
      patients, 33.9%), seizure (2 patients, 3.6%) and death (2 patients, 3.6%). There
      were differences between atypical versus typical groups in terms of age (62.1+/
      3.7 vs 51.0+/-2.9, p=0.020), ingested amounts (300 (IQR 100-338) cc vs 100 (IQR
      50-300) cc, p=0.002), and bicarbonate and serum lactate (17.4+/-1.1 vs 20.5+/
      0.4, p=0.011; and 4.42 (IQR 3.60-7.91) mmol/L vs 3.01 (IQR 2.16-4.73) mmol/L,
      p=0.010, respectively) in initial arterial blood gas analysis. Predictors of the
      atypical presentations were ingested amount and serum lactate ((OR 1.004, 95% CI
      1.001 to 1.008, p=0.013) and (OR 1.387, CI 1.074 to 1.791, p=0.012),
      respectively). The optimal points were 250 cc and 3.5 mmol/dL. CONCLUSIONS: 39.3%
      of pyrethroid poisoned patients had atypical presentations with the most common
      being respiratory failure requiring ventilator care. Predictors of atypical
      presentation were ingested amount >250 cc and serum lactate >3.5 mmol/L.

PMID- 23959806
TI  - The diadenosine homodinucleotide P18 improves in vitro myelination in
      experimental Charcot-Marie-Tooth type 1A.
AB  - Charcot-Marie-Tooth 1A (CMT1A) is a demyelinating hereditary neuropathy whose
      pathogenetic mechanisms are still poorly defined and an etiologic treatment is
      not yet available. An abnormally high intracellular Ca(2+) concentration
      ([Ca(2+)]i) occurs in Schwann cells from CMT1A rats (CMT1A SC) and is caused by
      overexpression of the purinoceptor P2X7. Normalization of the Ca(2+) levels
      through down-regulation of P2X7 appears to restore the normal phenotype of CMT1A
      SC in vitro. We recently demonstrated that the diadenosine 5',5'''-P1, P2
      diphosphate (Ap2A) isomer P18 behaves as an antagonist of the P2X7 purinergic
      receptor, effectively blocking channel opening induced by ATP. In addition, P18
      behaves as a P2Y11 agonist, inducing cAMP overproduction in P2Y11-overexpressing
      cells. Here we investigated the in vitro effects of P18 on CMT1A SC. We observed
      that basal levels of intracellular cAMP ([cAMP]i), a known regulator of SC
      differentiation and myelination, are significantly lower in CMT1A SC than in wild
      type (wt) cells. P18 increased [cAMP]i in both CMT1A and wt SC, and this effects
      was blunted by NF157, a specific P2Y11 antagonist. Prolonged treatment of
      organotypic dorsal root ganglia (DRG) cultures with P18 significantly increased
      expression of myelin protein zero, a marker of myelin production, in both CMT1A
      and wt cultures. Interestingly, P18 decreased the content of non-phosphorylated
      neurofilaments, a marker of axonal damage, only in CMT1A DRG cultures. These
      results suggest that P2X7 antagonists, in combination with [cAMP]i-increasing
      agents, could represent a therapeutic strategy aimed at correcting the molecular
      derangements causing the CMT1A phenotype.

PMID- 23959807
TI  - A retrospective look at replacing face-to-face embryology instruction with online
      lectures in a human anatomy course.
AB  - Embryology is integrated into the Clinically Oriented Anatomy course at the Texas
      Tech University Health Sciences Center School of Medicine. Before 2008, the same
      instructor presented embryology in 13 face-to-face lectures distributed by organ
      systems throughout the course. For the 2008 and 2009 offerings of the course, a
      hybrid embryology instruction model with four face-to-face classes that
      supplemented online recorded lectures was used. One instructor delivered the
      lectures face-to-face in 2007 and by online videos in 2008-2009, while a second
      instructor provided the supplemental face-to-face classes in 2008-2009. The same
      embryology learning objectives and selected examination questions were used for
      each of the three years. This allowed direct comparison of learning outcomes, as
      measured by examination performance, for students receiving only face-to-face
      embryology instruction versus the hybrid approach. Comparison of the face-to-face
      lectures to the hybrid approach showed no difference in overall class performance
      on embryology questions that were used all three years. Moreover, there was no
      differential effect of the delivery method on the examination scores for bottom
      quartile students. Students completed an end-of-course survey to assess their
      opinions. They rated the two forms of delivery similarly on a six-point Likert
      scale and reported that face-to-face lectures have the advantage of allowing them
      to interact with the instructor, whereas online lectures could be paused,
      replayed, and viewed at any time. These experiences suggest the need for well
      designed prospective studies to determine whether online lectures can be used to
      enhance the efficacy of embryology instruction.

PMID- 23959808
TI  - Superior mesenteric artery syndrome and its associated gastrointestinal
      implications.
AB  - The superior mesenteric artery (SMA) syndrome is a rare but potentially life
      threatening gastrointestinal condition. Over the years, it has been referenced by
      several names, the most common of which is Wilkie's syndrome. These numerous
      terminologies have made it difficult to estimate its true frequency in the
      general population. Common symptoms associated with this syndrome include
      intermittent postprandial abdominal pain, nausea, and bilious vomiting. Our
      review revealed that although it is currently well-defined in the literature, the
      diagnosis of SMA syndrome remains challenging as other disorders can mimic its
      presentation. However, CT angiography is currently favored in the literature for
      diagnosis as it can not only show the narrowed aorto-mesenteric angle and
      distance, but also the extent of duodenal obstruction. In addition, we found no
      consensus on the preferred mode of therapy once SMA syndrome is diagnosed. The
      agreement among authors is that the treatment options should be based on severity
      of the disease, using conservative measures as the first line of therapy in mild
      SMA syndrome. Duodenojejunostomy is the preferred surgical approach when
      conservative management fails, or in severe cases.

PMID- 23959809
TI  - HLA in Georgians (Caucasus) and their relationship with Eastern Mediterraneans.
AB  - HLA-A, -B, -DQB1, and -DRB1 typing has been performed in a sample of Georgian
      population (South Caucasus). Allele frequencies, neighbour joining and
      correspondence relatedness analyses and extended HLA haplotypes have been
      obtained with comparison with other Middle East and Mediterranean populations.
      Our Georgian sample tends to be genetically related in these analyses with
      Eastern Mediterraneans and Middle East people. This is important for future
      regional transplant programs, and Georgian HLA and disease epidemiology and
      pharmacogenomics.

PMID- 23959810
TI  - Sex differences in DNA methylation may contribute to risk of PTSD and depression:
      a review of existing evidence.
AB  - There are well-established sex differences in the prevalence of certain mental
      disorders. Work in animal models has provided us with an emerging understanding
      of the role that epigenetic factors play in establishing sex differences in the
      brain during development. Similarly, work in animal models, and a more limited
      but growing literature based on human studies, has demonstrated that DNA
      methylation (DNAm) changes occur in response to environmental stress, with some
      of these occurring in a sex-specific manner. In this review, we explore whether
      DNAm plays a role in contributing to the observed sex differences in prevalence
      of mental disorders in which stress contributes significantly to their
      etiologies, specifically posttraumatic stress disorder (PTSD) and depression. We
      propose that investigating sex differences in DNAm among genes known to influence
      brain development may help to shed light on the sexually dimorphic risk for, or
      resilience to, developing PTSD and depression.

PMID- 23959812
TI  - Real-time metabolic monitoring with proton transfer reaction mass spectrometry.
AB  - We analysed the time evolution of several volatile organic compounds formed by
      the catabolism of ingested isotope-labelled ethanol using real-time breath gas
      analysis with proton-transfer-reaction mass spectrometry. Isotope labelling
      allowed distinguishing the emerging volatile metabolites from their naturally
      occurring, highly abundant counterparts in the human breath. Due to an extremely
      low detection limit of the employed technologies in the parts per trillion per
      volume range, it was possible to detect the emerging metabolic products in
      exhaled breath within ~10 min after oral ingestion of isotope-labelled ethanol.
      We observed that ethanol was in part transformed into deuterated acetone and
      isoprene, reflecting the different fates of activated acetic acid (acetyl
      coenzyme A), formed in ethanol metabolism. Using ethanol as a model clearly
      demonstrated the value of the here presented technique for the search for
      volatile markers for metabolic disorders in the exhaled breath and its potential
      usefulness in the diagnosis and monitoring of such diseases. 

PMID- 23959811
TI  - Hematopoietic stem cell transplantation for acute myeloid leukemia: to whom,
      when, and how.
AB  - Allogeneic hematopoietic stem cell transplant (HSCT) is an established treatment
      modality with curative potential for acute myeloid leukemia (AML). There has been
      a significant rise in the number of HSCT procedures performed over the past
      decade due in part to improved supportive care and innovative techniques such as
      reduced-intensity conditioning. Expanding alternative donor options such as
      umbilical cord blood and haploidentical HSCT, taken together with improved
      outcomes of matched unrelated donors, has resulted in a suitable donor for most
      patients with an HSCT indication. Recent advances in molecular diagnostics that
      incorporate genetic mutational analysis into existing cytogenetic-based models
      should improve selection of patients at high risk of relapse most likely to
      benefit from HSCT. Improvements in minimal residual disease monitoring hold
      promise for adding prognostic information, and informing the clinician of
      impending relapse. The choice of the conditioning regimen involves weighing a
      patient's unique toxicity and relapse risks. Despite improvements, relapse
      remains the primary source of treatment failure after HSCT for treatment of AML.
      The introduction of novel therapies into the clinic, together with improved
      patient selection, offers hope for decreasing relapse and improving outcomes for
      AML patients.

PMID- 23959813
TI  - Local Li coordination and ionic transport in methacrylate-based gel polymer
      electrolytes.
AB  - The local Li cation coordination motifs and the interactions between the hosting
      methacrylate-based polymer membrane and the liquid electrolyte [1 M LiPF6 in
      ethylene carbonate (EC)/dimethyl carbonate (DMC)] are studied by employing liquid
      and solid-state NMR spectroscopy. At low temperatures, two different coordination
      modes for Li cations are identified with the help of dipolar-based solid-state
      NMR techniques, one of which is the exclusive coordination by DMC molecules,
      while the other is a co-coordination by the polymer and DMC molecules. At room
      temperature, Li cations are found to be extremely mobile, coordinated by EC and
      DMC molecules as well as the copolymer, as found by liquid-state NMR
      spectroscopy.

PMID- 23959814
TI  - Use of a structured medication history to establish medication use at admission
      to an old age psychiatric clinic: a prospective observational study.
AB  - OBJECTIVE: Medication reconciliation results in fewer adverse drug events. The
      first step in medication reconciliation is to carry out a structured interview
      about medication use. It is not known whether such an interview is useful in
      inpatient old age psychiatry. The object of this study was to determine at
      admission the number of discrepancies in medication use, comparing the structured
      history of medication use (SHIM) procedure with the usual procedure for taking
      the medication history. METHODS: A prospective observational study was conducted.
      All consecutive patients aged 55 years and older admitted from January until
      April 2011 to the inpatient old age psychiatric clinic of a large psychiatric
      teaching hospital in The Hague, the Netherlands, were eligible for inclusion; 50
      patients were included. In every patient, the usual procedure (medication history
      taking at admission by the treating physician) was compared with the SHIM
      procedure administered by the researcher. The SHIM procedure consists of a
      structured interview with the patient about the actual use of medication,
      incorporating the information from the community pharmacy and the patient's
      medications brought to the interview. The main outcome was the number of
      discrepancies in recorded medication use between the SHIM and the usual
      procedure. RESULTS: In total, 100 discrepancies (median 2 per patient, range 0-8)
      in medication use were identified; 78 % (n = 39) of the patients had at least one
      discrepancy. Of the discrepancies, 69 % were drug omissions, and 31 % were drug
      additions or discrepancies in the frequency or dosage of medications. Eighty-two
      percent of all discrepancies were potentially clinically relevant. In 24 % of the
      patients, the discrepancies had clinical consequences. CONCLUSION: The number of
      discrepancies that were found suggests that the usual procedure for taking the
      medication history can be improved. The SHIM procedure enables a comprehensive
      and accurate overview of the medication used by older patients admitted to a
      psychiatric hospital, and contributes to the prevention of clinically relevant
      adverse drug events.

PMID- 23959815
TI  - Efficacy and safety of lisdexamfetamine dimesylate and atomoxetine in the
      treatment of attention-deficit/hyperactivity disorder: a head-to-head,
      randomized, double-blind, phase IIIb study.
AB  - OBJECTIVES: The aim of this study was to compare the efficacy and safety of the
      prodrug psychostimulant lisdexamfetamine dimesylate (LDX) and the non-stimulant
      noradrenergic compound atomoxetine (ATX) in children and adolescents with
      attention-deficit/hyperactivity disorder (ADHD) who had previously responded
      inadequately to methylphenidate (MPH). METHODS: This 9-week, head-to-head,
      randomized, double-blind, active-controlled study (SPD489-317; ClinicalTrials.gov
      NCT01106430) enrolled patients (aged 6-17 years) with at least moderately
      symptomatic ADHD and an inadequate response to previous MPH therapy. Patients
      were randomized (1:1) to an optimized daily dose of LDX (30, 50 or 70 mg) or ATX
      (patients <70 kg, 0.5-1.2 mg/kg with total daily dose not to exceed 1.4 mg/kg;
      patients >=70 kg, 40, 80 or 100 mg). The primary efficacy outcome was time (days)
      to first clinical response. Clinical response was defined as a Clinical Global
      Impressions-Improvement (CGI-I) score of 1 (very much improved) or 2 (much
      improved). Secondary efficacy outcomes included the proportion of responders at
      each study visit and the change from baseline in ADHD Rating Scale (ADHD-RS-IV)
      and CGI-Severity scores. Tolerability and safety were assessed by monitoring
      treatment-emergent adverse events (TEAEs), height and weight, vital signs and
      electrocardiogram parameters. Endpoint was defined as the last post-baseline, on
      treatment visit with a valid assessment. RESULTS: Of 267 patients randomized
      (LDX, n = 133; ATX, n = 134), 200 (74.9%) completed the study. The median time to
      first clinical response [95% confidence interval (CI)] was significantly shorter
      for patients receiving LDX [12.0 days (8.0-16.0)] than for those receiving ATX
      [21.0 days (15.0-23.0)] (p = 0.001). By week 9, 81.7% (95% CI 75.0-88.5) of
      patients receiving LDX had responded to treatment compared with 63.6% (95% CI
      55.4-71.8) of those receiving ATX (p = 0.001). Also by week 9, the difference
      between LDX and ATX in least-squares mean change from baseline (95% CI) was
      significant in favour of LDX for the ADHD-RS-IV total score [-6.5 (-9.3 to -3.6);
      p < 0.001; effect size 0.56], inattentiveness subscale score [-3.4 (-4.9 to 
      1.8); p < 0.001; effect size 0.53] and the hyperactivity/impulsivity subscale
      score [-3.2 (-4.6 to -1.7); p < 0.001; effect size 0.53]. TEAEs were reported by
      71.9 and 70.9% of patients receiving LDX and ATX, respectively. At endpoint, both
      treatments were associated with mean (standard deviation) increases in systolic
      blood pressure [LDX, +0.7 mmHg (9.08); ATX, +0.6 mmHg (7.96)], diastolic blood
      pressure [LDX, +0.1 mmHg (8.33); ATX, +1.3 mmHg (8.24)] and pulse rate [LDX, +3.6
      bpm (10.49); ATX, +3.7 bpm (10.75)], and decreases in weight [LDX, -1.30 kg
      (1.806); ATX, -0.15 kg (1.434)]. CONCLUSIONS: LDX was associated with a faster
      and more robust treatment response than ATX in children and adolescents with at
      least moderately symptomatic ADHD who had previously responded inadequately to
      MPH. Both treatments displayed safety profiles consistent with findings from
      previous clinical trials.

PMID- 23959816
TI  - Foreign body impaction as presentation of eosinophilic esophagitis.
AB  - Esophageal foreign body is a frequent pediatric presentation, and eosinophilic
      esophagitis (EoE) is an important underlying disease. To determine
      characteristics common in the presentation of esophageal foreign body indicative
      of underlying EoE and reach a recommendation for the appropriate scenario in
      which to obtain esophageal mucosal biopsy, 312 pediatric esophageal foreign
      bodies requiring operative removal were reviewed. Patients older than 18 years or
      with a known history of esophageal surgery or pathology were excluded.
      Eligibility criteria were met in 271 cases. Twenty-seven patients were biopsied,
      and 18 were diagnosed with EoE. The following factors were identified in the EoE
      population: food impaction (89%), older age (average 12.2 years), male sex (78%),
      atopic disease (61%), previous esophageal foreign body or frequent dysphagia
      (83%), and endoscopic abnormalities (100%). These factors are all associated with
      an underlying diagnosis of EoE, and patients meeting these criteria should be
      strongly considered for intraoperative esophageal mucosal biopsy. 

PMID- 23959817
TI  - Therapeutic efficacy of the combination of intratympanic methylprednisolone and
      oral steroid for idiopathic sudden deafness.
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy of systemic
      steroid alone and combined with intratympanic methylprednisolone in the treatment
      of patients with idiopathic sudden sensorineural hearing loss. STUDY DESIGN:
      Prospective, randomized controlled trial. Settings Katip Celebi University
      Ataturk Training and Research Hospital, Izmir, Turkey. SUBJECT AND METHODS:
      Seventy-nine patients who met the inclusion criteria for idiopathic sudden
      sensorineural hearing loss were included in this study. Patients were randomly
      divided into 2 groups according to treatment: group A received combination
      therapy (intratympanic methylprednisolone + oral steroid) and group B received
      oral steroid alone. Of the 79 patients included, 6 patients missed the 1-month
      follow-up visit. Overall, 73 patients (37 combination group, 36 oral steroid
      group) who completed the 1-month follow-up and study intervention were included
      in the per-protocol analysis. Both the relationship between certain prognostic
      factors and the clinical outcome after treatment were analyzed. RESULTS:
      Combination therapy showed significant hearing improvement and speech
      discrimination scores compared with the use of systemic steroids alone (P < .05).
      In hearing outcomes in patients with severe hearing loss, combination therapy had
      statistically significant hearing improvement compared with oral steroid alone (P
      < .05). CONCLUSION: We recommend that combination therapy can be considered as
      initial treatment especially for patients with severe hearing loss.

PMID- 23959818
TI  - Social media's role in otolaryngology-head and neck surgery: informing
      clinicians, empowering patients.
AB  - With the increasing availability of the Internet in the United States, patients
      are more frequently seeking medical information online. Oftentimes, the medical
      information that patients find on traditional websites is unreliable. It is a
      physician's duty to ensure that patients are being educated properly. Providing
      sound medical information through social media websites is one way in which
      physicians may accomplish this goal, while also improving clinic reputation,
      patient volume, and doctor-patient communication. 

PMID- 23959819
TI  - Treatment of chronic maxillary atelectasis using balloon dilation.
AB  - Balloon dilation may offer a more expedient and cost-effective treatment method
      compared with traditional endoscopic sinus surgery for chronic maxillary
      atelectasis. We sought to demonstrate the feasibility of balloon dilation of the
      maxillary os as a treatment modality for patients with chronic maxillary
      atelectasis by investigating the short-term outcomes in a retrospective case
      series of 4 patients representing 5 sinuses treated between 2011 and 2013. All
      sinuses were successfully balloon dilated without complications. Follow-up ranged
      from 1 week to 4 months. Aeration of the treated sinuses without restenosis was
      confirmed by postoperative endoscopy, sinus computed tomography, or both. All
      patients reported subjective symptomatic improvement. Balloon dilation of the
      maxillary os may be a feasible treatment option for maxillary sinus atelectasis.
      Longer follow-up and a larger study sample will be needed to validate the safety
      of this technique and determine the rate of restenosis. 

PMID- 23959820
TI  - Treatment of oral cavity venous malformations with the Nd:YAG laser using the
      underwater technique.
AB  - Mucosal involvement of venous malformations can cause bleeding, pain, and
      functional impairment. Treatment options include surgery, sclerotherapy, or laser
      therapy. Neodymium:yttrium aluminum garnet (Nd:Yag) laser therapy has been used
      to treat mucosal disease, but few studies have focused purely on the oral cavity.
      We present a retrospective review of 4 patients (5 subsites) with oral cavity
      venous malformations treated with the Nd:YAG laser using an underwater technique.
      Photographs of the venous malformations before and after treatment were evaluated
      by 2 blinded physicians. A visual analog scale was used to rate the treatment.
      The medical record was reviewed to assess change in symptoms and to note
      complications. Four sites were rated as having "significant improvement" and 1
      site as "some improvement." Our study demonstrates that the Nd:YAG laser can be a
      feasible option in the treatment of venous malformations of the oral cavity. 

PMID- 23959821
TI  - Severity of voice handicap in children diagnosed with elevated lesions.
AB  - OBJECTIVE: This study sought to determine the impact of voice disability on
      children with elevated vocal fold lesions (nodules, cysts, polyps). The Pediatric
      Voice Handicap Index (pVHI) was used to assess the impact on functional,
      physical, and emotional aspects of voice and oral communication. The degree of
      talkativeness and overall severity of dysphonia were also determined. STUDY
      DESIGN: Case series with chart review of children evaluated at a voice clinic
      from 2007 to 2011. SETTING: Tertiary specialized children's hospital. SUBJECTS
      AND METHODS: Medical records of 33 children (11 girls, 22 boys) diagnosed with an
      elevated vocal fold lesion by a pediatric laryngologist were reviewed for voice
      disability using the pVHI. The pVHI is a parental proxy of perceived voice
      handicap in functional, physical, and emotional aspects and includes a
      talkativeness rating scale and visual analog overall severity rating of voice
      (VAS). Data were examined for young children (age 2-5 years), children (age 6-10
      years), and adolescents (age 11-17 years). RESULTS: The VAS was significantly
      correlated with pVHI-total. There was no significant difference between age
      groups for overall pVHI (mean, 29.3) or talkativeness, but all groups had
      significantly higher functional disability (mean, 16) compared with physical
      (mean, 8.2) or emotional (mean, 5.1) disability. CONCLUSIONS: Children across all
      age groups with elevated vocal fold lesions have significant voice disability,
      greatest for functional aspects of voice. Voice care team professionals must
      recognize the functional impact of dysphonia on the pediatric patient.

PMID- 23959822
TI  - Novel diagnostic method for oroantral fistulas.

PMID- 23959823
TI  - HSF1 and Sp1 regulate FUT4 gene expression and cell proliferation in breast
      cancer cells.
AB  - Lewis Y (LeY) is a carbohydrate tumor-associated antigen. The majority of cancer
      cells derived from epithelial tissues express LeY type difucosylated
      oligosaccharides. Fucosyltransferase IV (FUT4) is an essential enzyme that
      catalyzes the synthesis of LeY oligosaccharides. In a previous study we reported
      that FUT4 is associated with cell proliferation; however, despite the important
      role of FUT4 in cancer proliferation and apoptosis, little is known about the
      mechanisms underlying the regulation of FUT4 transcription. In the current study
      we investigated the regulation of FUT4 transcription in human breast cancer. We
      compared the regulation of human FUT4 gene transcription in human breast cancer
      cells (MCF-7 and MDA-MB-231) using promoter/luciferase analyses. Using a series
      of promoter deletion constructs, we identified a potential regulatory site
      located between 0.8 and 1.6 kb of the FUT4 promoter. As shown by EMSA and ChIP
      analyses, heat-shock factor 1 (HSF1) and Sp1are required for FUT4 promoter
      activity. In addition, we explored the role of HSF1 and Sp1 on cell
      proliferation, and found that the ERK1/2 MAPK and PI3K/Akt signaling pathways
      regulate the expression of FUT4, which play a role in cell proliferation via HSF1
      and Sp1. These results suggest that FUT4 is a target gene for HSF1 and Sp1 that
      is required for cell cycle progression in breast cancer epithelial cells.

PMID- 23959824
TI  - First curl, then wrinkle.
AB  - The excellent properties of elastomers are exploited to trigger wrinkling
      instabilities in curved shells. Micro- and nano-fibres are produced by
      electrospinning and UV irradiated: each fibre consists of a soft core and a stiff
      outer half-shell. Upon solvent de-swelling, the fibres curl because the shell and
      the core have different natural lengths. Wrinkling only starts after the fibre
      has attained a well-defined helical shape. A simple analytical model is proposed
      to find the curling curvature and wrinkle wavelength, as well as the transition
      between the "curling" and "wrinkling" regimes. This new instability resembles
      that found in the tendrils of climbing plants as they dry and lignify. 

PMID- 23959825
TI  - Respiratory virus RNA is detectable in airborne and droplet particles.
AB  - Aerosol transmission routes of respiratory viruses have been classified by the
      WHO on the basis of equilibrium particle size. Droplet transmission is associated
      with particles sized >5 um in diameter and airborne transmission is associated
      with particles sized <=5 um in diameter. Current infection control measures for
      respiratory viruses are directed at preventing droplet transmission, although
      epidemiological evidence suggests concurrent airborne transmission also occurs.
      Understanding the size of particles carrying viruses can be used to inform
      infection control procedures and therefore reduce virus transmission. This study
      determined the size of particles carrying respiratory viral RNA produced on
      coughing and breathing by 12 adults and 41 children with symptomatic respiratory
      infections. A modified six-stage Andersen Sampler collected expelled particles.
      Each stage was washed to recover samples for viral RNA extraction. Influenza A
      and B, parainfluenza 1, 2 and 3, respiratory syncytial virus (RSV), human
      metapneumovirus and human rhinoviruses (hRV) were detected using RT-PCR. On
      breathing, 58% of participants produced large particles (>5 um) containing viral
      RNA and 80% produced small particles (<=5 um) carrying viral RNA. On coughing,
      57% of participants produced large particles containing viral RNA and 82%
      produced small particles containing viral RNA. Forty five percent of participants
      produced samples positive for hRV viral RNA and 26% of participants produced
      samples positive for viral RNA from parainfluenza viruses. This study
      demonstrates that individuals with symptomatic respiratory viral infections
      produce both large and small particles carrying viral RNA on coughing and
      breathing.

PMID- 23959826
TI  - How the ASNC ImageGuide Registry will guide healthcare policy.

PMID- 23959827
TI  - Is there a role for myocardial perfusion imaging in patients with an elevated
      high-sensitivity troponin?

PMID- 23959828
TI  - Starmerella neotropicalis f. a., sp. nov., a yeast species found in bees and
      pollen.
AB  - A novel yeast species was found repeatedly and in high cell densities in
      underground-nesting stingless bees of the species Melipona quinquefasciata and
      their provisions in northern Minas Gerais (Brazil). One additional strain was
      isolated from bee-collected pollen in Cuba. Phylogenetic analyses based on rRNA
      gene sequences (D1/D2 large subunit gene and internal transcribed spacer)
      indicated that the novel species belongs to the Starmerella clade and is most
      closely related to Candida (iter. nom. Starmerella) apicola. Growth reactions on
      carbon and nitrogen sources were typical of those observed in related species of
      the Starmerella clade. PCR-fingerprinting with mini- and microsatellite specific
      primers allowed the distinction of the novel species from Candida apicola,
      Candida bombi and a yet undescribed species represented by strain CBS 4353. On
      the basis of phylogenetic relationships, the novel species is assigned to the
      genus Starmerella despite the failure to observe sexual reproduction after
      extensive mating tests. We propose the name Starmerella neotropicalis f. a., sp.
      nov. (Mycobank MB 804285) and designate UFMG PST 09(T) ( = MUCL 53320(T) = CBS
      12811(T)) as the type strain. 

PMID- 23959829
TI  - Mesoaciditoga lauensis gen. nov., sp. nov., a moderately thermoacidophilic member
      of the order Thermotogales from a deep-sea hydrothermal vent.
AB  - A novel moderately thermophilic, heterotrophic bacterium was isolated from a deep
      sea hydrothermal vent deposit from the Mariner field along the Eastern Lau
      Spreading Center of the south-western Pacific Ocean. Cells were short motile rods
      (about 0.4*0.8 um) that occurred singly or in pairs and were surrounded by a
      sheath-like membrane or 'toga'. The cells grew between 45 and 65  degrees C
      (optimum 57-60  degrees C) and at pH 4.1-6.0 (optimum pH 5.5-5.7) and grew
      optimally at 3 % (w/v) NaCl. The isolate grew on a range of carbon and
      proteinaceous substrates and reduced sulfur. The G+C content of the DNA was about
      45 mol%. Phylogenetic analysis of the 16S rRNA gene sequence placed the new
      isolate as a deeply diverging lineage within the order Thermotogales. Based on
      the physiological, morphological and phylogenetic data, the isolate represents a
      novel species of a new genus with the proposed name Mesoaciditoga lauensis gen.
      nov., sp. nov. The type strain of Mesoaciditoga lauensis is cd-1655R(T) ( = DSM
      25116(T) = OCM 1212(T)). 

PMID- 23959830
TI  - Enterococcus saccharolyticus subsp. taiwanensis subsp. nov., isolated from
      broccoli.
AB  - A coccal strain isolated from fresh broccoli was initially identified as
      Enterococcus saccharolyticus; however, molecular identification and phenotypic
      traits did not support this identification. DNA-DNA hybridization with the type
      strain of E. saccharolyticus (76.4 % relatedness), DNA G+C content (35.7 mol%),
      phylogenetic analysis based on 16S rRNA, pheS and rpoA gene sequences, rep-PCR
      fingerprinting and profiles of cellular fatty acids, whole-cell proteins and
      enzyme activities, together with carbohydrate metabolism characteristics,
      indicated that this strain is distinct and represents a novel subspecies, for
      which the name Enterococcus saccharolyticus subsp. taiwanensis subsp. nov. is
      proposed. The type strain is 812(T) ( = NBRC 109476(T) = BCRC 80575(T)).
      Furthermore, we present an emended description of Enterococcus saccharolyticus
      and proposal of Enterococcus saccharolyticus subsp. saccharolyticus subsp. nov.
      (type strain ATCC 43076(T) = CCUG 27643(T) = CCUG 33311(T) = CIP 103246(T) = DSM
      20726(T) = JCM 8734(T) = LMG 11427(T) = NBRC 100493(T) = NCIMB 702594(T)). 

PMID- 23959831
TI  - Burkholderia humi sp. nov., Burkholderia choica sp. nov., Burkholderia telluris
      sp. nov., Burkholderia terrestris sp. nov. and Burkholderia udeis sp. nov.:
      Burkholderia glathei-like bacteria from soil and rhizosphere soil.
AB  - Analysis of partial gyrB gene sequences revealed six taxa in a group of 17
      Burkholderia glathei-like isolates which were further examined by (GTG)5-PCR
      fingerprinting, 16S rRNA gene sequence analysis, DNA-DNA hybridizations,
      determination of the DNA G+C content, whole-cell fatty acid analysis and an
      analysis of cell and colony morphology and more than 180 biochemical
      characteristics. The results demonstrated that one taxon consisting of three
      human clinical isolates represented Burkholderia zhejiangensis, a recently
      described methyl-parathion-degrading bacterium isolated from a wastewater
      treatment system in China. The remaining taxa represented five novel species
      isolated from soil or rhizosphere soil samples, and could be distinguished by
      both genotypic and phenotypic characteristics. We therefore propose to formally
      classify these bacteria as Burkholderia humi sp. nov. (type strain, LMG 22934(T)
      = CCUG 63059(T)), Burkholderia choica sp. nov. (type strain, LMG 22940(T) = CCUG
      63063(T)), Burkholderia telluris sp. nov. (type strain, LMG 22936(T) = CCUG
      63060(T)), Burkholderia udeis sp. nov. (type strain, LMG 27134(T) = CCUG
      63061(T)) and Burkholderia terrestris sp. nov. (type strain, LMG 22937(T) = CCUG
      63062(T)). 

PMID- 23959832
TI  - Streptomyces yaanensis sp. nov., isolated from soil.
AB  - A novel actinomycete, designated Z4(T), was isolated from soil in Yaan, Sichuan
      Province, south China. The taxonomic status of this strain was established using
      a polyphasic approach. The morphological and chemotaxonomic characteristics of
      the organism are typical of the members of the genus Streptomyces. Phylogenetic
      analysis based on the almost complete 16S rRNA gene sequence indicated that
      strain Z4(T) belonged to the genus Streptomyces, branching off next to
      Streptomyces durhamensis ATCC 23194(T) (98.7 %), Streptomyces puniciscabiei KACC
      20253(T) (98.7 %) and Streptomyces filipinensis ATCC 23905(T) (98.6 %). However,
      DNA-DNA hybridization studies and phenotypic differences between strain Z4(T) and
      closely related species of the genus Streptomyces suggested that strain Z4(T)
      represented a different genomic species. It is therefore proposed that Z4(T) ( =
      CGMCC 4.7035(T) = KCTC 29111(T)) represents the type strain of a novel species of
      the genus Streptomyces, for which the name Streptomyces yaanensis sp. nov. is
      proposed. 

PMID- 23959834
TI  - Institutional charges and disparities in outpatient brain biopsies in four US
      States: the State Ambulatory Database (SASD).
AB  - Several groups have demonstrated the safety of ambulatory brain biopsies, with no
      patients experiencing complications related to early discharge. Although they
      appear to be safe, the reasons factoring into the selection of patients have not
      been investigated. We performed a cross-sectional study involving 504 patients
      who underwent outpatient and 10,328 patients who underwent inpatient brain
      biopsies and were registered in State Ambulatory Surgery Databases and State
      Inpatient Databases respectively for four US States (New York, California,
      Florida, North Carolina). In a multivariate analysis private insurance (OR 2.45,
      95 % CI, 1.85, 3.24), was significantly associated with outpatient procedures.
      Higher Charlson Comorbidity Index (OR 0.16, 95 % CI, 0.08, 0.32), high income (OR
      0.37, 95 % CI, 0.26, 0.53), and high volume hospitals (OR 0.30, 95 % CI, 0.23,
      0.39) were associated with a decreased chance of outpatient procedures. No sex,
      or racial disparities were observed. Institutional charges were significantly
      less for outpatient brain biopsies. There was no difference in the rate of 30-day
      postoperative readmissions among inpatient and outpatient procedures. The median
      charge for inpatient surgery was 51,316 as compared to 12,266 for the outpatient
      setting (P < 0.0001, Student's t test). Access to ambulatory brain biopsies
      appears to be more common for patients with private insurance and less
      comorbidities, in the setting of lower volume hospitals. Further investigation is
      needed in the direction of mapping these disparities in resource utilization.

PMID- 23959833
TI  - 5,10-Methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and
      methionine synthase reductase (MTR) gene polymorphisms and adult meningioma risk.
AB  - The causes of meningiomas are not well understood. Folate metabolism gene
      polymorphisms have been shown to be associated with various human cancers. It is
      still controversial and ambiguous between the functional polymorphisms of folate
      metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine
      synthase (MTRR), and methionine synthase reductase (MTR) and risk of adult
      meningioma. A population-based case-control study involving 600 meningioma
      patients (World Health Organization [WHO] Grade I, 391 cases; WHO Grade II, 167
      cases; WHO Grade III, 42 cases) and 600 controls was done for the MTHFR C677T and
      A1298C, MTRR A66G, and MTR A2756G variants in Chinese Han population. The folate
      metabolism gene polymorphisms were determined by using a polymerase chain
      reaction-restriction fragment length polymorphism assay. Meningioma cases had a
      significantly lower frequency of MTHFR 677 TT genotype [odds ratio (OR) = 0.49,
      95 % confidence interval (CI) 0.33-0.74; P = 0.001] and T allele (OR = 0.80, 95 %
      CI 0.67-0.95; P = 0.01) than controls. A significant association between risk of
      meningioma and MTRR 66 GG (OR = 1.41, 95 % CI 1.02-1.96; P = 0.04) was also
      observed. When stratifying by the WHO grade of meningioma, no association was
      found. Our study suggested that MTHFR C677T and MTRR A66G variants may affect the
      risk of adult meningioma in Chinese Han population.

PMID- 23959835
TI  - A practical approach to difficult urinary catheterizations.
AB  - Routine placement of transurethral catheters can be challenging in some
      situations, such as urethral strictures, severe phimosis and false passages.
      Intravaginal retraction of the urethral meatus can complicate Foley placement in
      postmenopausal females. In men, blind urethral procedures with mechanical or
      metal sounds without visual guidance or guidewire assistance are now discouraged
      due to the increased risk of urethral trauma and false passages. Newer techniques
      of urethral catheterization including guidewires, directed hydrophilic mechanical
      dilators, urethral balloon dilation, and direct vision endoscopic catheter
      systems are discussed, along with the new standardized protocol for difficult
      transurethral catheter insertions. Suprapubic catheter placement techniques,
      including percutaneous trocars and the use of the curved Lowsley tractor for
      initial suprapubic catheter insertion, are reviewed. Prevention and management of
      common catheter-related problems such as encrustation, leakage, Foley
      malposition, balloon cuffing and frequent blockages are discussed.

PMID- 23959836
TI  - Brachial plexus anesthesia: A review of the relevant anatomy, complications, and
      anatomical variations.
AB  - The trend towards regional anesthesia began in the late 1800s when William
      Halsted and Richard Hall experimented with cocaine as a local anesthetic for
      upper and lower limb procedures. Regional anesthesia of the upper limb can be
      achieved by blocking the brachial plexus at varying stages along the course of
      the trunks, divisions, cords and terminal branches. The four most common
      techniques used in the clinical setting are the interscalene block, the
      supraclavicular block, the infraclavicular block, and the axillary block. Each
      approach has its own unique set of advantages and indications for use. The
      supraclavicular block is most effective for anesthesia of the mid-humerus and
      below. Infraclavicular blocks are useful for procedures requiring continuous
      anesthesia. Axillary blocks provide effective anesthesia distal to the elbow, and
      interscalene blocks are best suited for the shoulder and proximal upper limb. The
      two most common methods for localizing the appropriate nerves for brachial plexus
      blocks are nerve stimulation and ultrasound guidance. Recent literature on
      brachial plexus blocks has largely focused on these two techniques to determine
      which method has greater efficacy. Ultrasound guidance has allowed the operator
      to visualize the needle position within the musculature and has proven especially
      useful in patients with anatomical variations. The aim of this study is to
      provide a review of the literature on the different approaches to brachial plexus
      blocks, including the indications, techniques, and relevant anatomical variations
      associated with the nerves involved.

PMID- 23959837
TI  - Reporting of ethical requirements in phase III surgical trials.
AB  - BACKGROUND: Disclosure of obtaining informed consent from patients (ICP) and
      research ethics committee (REC) approval in published reports is sometimes
      omitted. To date, no disclosure data are available on surgical research.
      OBJECTIVE: Our aim was to assess whether REC approval and ICP were documented in
      surgical trials. STUDY DESIGN: Overall, 657 randomised trials, published between
      2005 and 2010 in 10 international journals, were included. We collected the
      report rate of REC approval and ICP and contacted the corresponding author when
      ethical information was lacking. RESULTS: Among the 657 randomised controlled
      trials (RCT), 576 (87.7%) stated that an REC had approved the research, and 606
      (92.2%) stated that ICP had been requested. Furthermore, 28 RCTs (4.3%) reported
      neither REC nor ICP. CONCLUSIONS: The phase III randomised surgical trials that
      were analysed were shown to have respected fundamental ethical principles in
      approximately 90% of the cases examines.

PMID- 23959838
TI  - Consensus standards for introductory e-learning courses in human participants
      research ethics.
AB  - This paper reports the results of a workshop held in January 2013 to begin the
      process of establishing standards for e-learning programmes in the ethics of
      research involving human participants that could serve as the basis of their
      evaluation by individuals and groups who want to use, recommend or accredit such
      programmes. The standards that were drafted at the workshop cover the following
      topics: designer/provider qualifications, learning goals, learning objectives,
      content, methods, assessment of participants and assessment of the course. The
      authors invite comments on the draft standards and eventual endorsement of a
      final version by all stakeholders. 

PMID- 23959839
TI  - Is dental phobia a blood-injection-injury phobia?
AB  - BACKGROUND: Dental phobia is part of the Blood-Injection-Injury (B-I-I) phobia
      subtype of specific phobia within DSM-IV-TR. To investigate the conceptual
      validity of this classification, the purpose of the present study was to
      determine the co-occurrence of dental phobia, typical dental (and B-I-I related)
      fears, vasovagal fainting, and avoidance of dental care. METHOD: Data were
      collected by an online survey in Dutch twin families (n = 11,213). RESULTS:
      Individuals with a positive screen of dental phobia (0.4% of the sample) rated
      typical B-I-I-related stimuli as relatively little anxiety provoking (e.g. of all
      28 fears the stimulus "the sight of blood" was ranked lowest). Presence of dental
      phobia was significantly associated with a history of dizziness or fainting
      during dental treatment (OR = 3.4; 95% CI: 1.5-8.1), but of the dental phobic
      individuals only 13.0% reported a history of dizziness or fainting during dental
      treatment. Presence of dental phobia (OR = 5.0; 95% CI: 2.8-8.8) was found to be
      associated with avoidance of dental care, but a history of dizziness or fainting
      during dental treatment was not (OR = 1.0; 95% CI: 0.8-1.2). CONCLUSIONS: The
      present findings converge to the conclusion that dental phobia should be
      considered a specific phobia subtype independent of the B-I-I cluster within the
      DSM classification system.

PMID- 23959840
TI  - Is breath acetone a biomarker of diabetes? A historical review on breath acetone
      measurements.
AB  - Since the ancient discovery of the 'sweet odor' in human breath gas, pursuits of
      the breath analysis-based disease diagnostics have never stopped. Actually, the
      'smell' of the breath, as one of three key disease diagnostic techniques, has
      been used in Eastern-Medicine for more than three thousand years. With
      advancement of measuring technologies in sensitivity and selectivity, more
      specific breath gas species have been identified and established as a biomarker
      of a particular disease. Acetone is one of the breath gases and its concentration
      in exhaled breath can now be determined with high accuracy using various
      techniques and methods. With the worldwide prevalence of diabetes that is
      typically diagnosed through blood testing, human desire to achieve non-blood
      based diabetic diagnostics and monitoring has never been quenched. Questions,
      such as is breath acetone a biomarker of diabetes and how is the breath acetone
      related to the blood glucose (BG) level (the golden criterion currently used in
      clinic for diabetes diagnostic, monitoring, and management), remain to be
      answered. A majority of current research efforts in breath acetone measurements
      and its technology developments focus on addressing the first question. The
      effort to tackle the second question has begun recently. The earliest breath
      acetone measurement in clearly defined diabetic patients was reported more than
      60 years ago. For more than a half-century, as reviewed in this paper, there have
      been more than 41 independent studies of breath acetone using various techniques
      and methods, and more than 3211 human subjects, including 1581 healthy people,
      242 Type 1 diabetic patients, 384 Type 2 diabetic patients, 174 unspecified
      diabetic patients, and 830 non-diabetic patients or healthy subjects who are
      under various physiological conditions, have been used in the studies. The
      results of the breath acetone measurements collected in this review support that
      many conditions might cause changes to breath acetone concentrations; however,
      the results from the six independent studies using clearly-defined Type 1 and
      Type 2 diabetic patients unanimously support that an elevated mean breath acetone
      concentration exists in Type 1 diabetes. Note that there is some overlap between
      the ranges of breath acetone concentration in individual T1D patients and healthy
      subjects; this reminds one to be careful when using an acetone breath test on T1D
      diagnostics. Comparatively, it is too early to draw a general conclusion on the
      relationship between a breath acetone level and a BG level from the very limited
      data in the literature. 

PMID- 23959841
TI  - Optimal pharmacotherapeutic management of hormone-sensitive metastatic prostate
      cancer.
AB  - The mainstay of initial therapy of metastatic prostate cancer has not changed
      since 1941 when Huggins and Hodges described the efficacy of castration. The
      benefit of combining an androgen receptor blocker with medical castration has
      been debatable despite several large randomized trials and meta-analyses intended
      to answer the question. Recent phase III trial data with continuous versus
      intermittent androgen deprivation in newly diagnosed metastatic prostate cancer
      have established continuous therapy as the preferred approach at the present
      time. Novel and more potent inhibitors of androgen signaling have been developed
      in the past 5 years and have been validated in castration-resistant disease.
      Their role in management of hormone-sensitive metastatic prostate cancer is under
      evaluation in ongoing studies. As androgen deprivation therapy carries
      significant long-term toxicities including fatigue and loss of bone and muscle
      mass, an important element of clinical management is prevention and amelioration
      of these toxicities.

PMID- 23959842
TI  - Dye sublimation as a measure of accumulated heat exposure.
AB  - Heat history monitor: Combination of the sublimation and adsorption processes of
      specific dyes can be used as a measure of accumulated heat exposure. Mass
      transfer from the sublimation layer to the adsorption layer strongly depends on
      temperature and results in a gradual color change in the adsorption layer. The
      total color change reflects the accumulated heat exposure. 

PMID- 23959843
TI  - From vital signs to clinical outcomes for patients with sepsis: a machine
      learning basis for a clinical decision support system.
AB  - OBJECTIVE: To develop a decision support system to identify patients at high risk
      for hyperlactatemia based upon routinely measured vital signs and laboratory
      studies. MATERIALS AND METHODS: Electronic health records of 741 adult patients
      at the University of California Davis Health System who met at least two systemic
      inflammatory response syndrome criteria were used to associate patients' vital
      signs, white blood cell count (WBC), with sepsis occurrence and mortality.
      Generative and discriminative classification (naive Bayes, support vector
      machines, Gaussian mixture models, hidden Markov models) were used to integrate
      heterogeneous patient data and form a predictive tool for the inference of
      lactate level and mortality risk. RESULTS: An accuracy of 0.99 and
      discriminability of 1.00 area under the receiver operating characteristic curve
      (AUC) for lactate level prediction was obtained when the vital signs and WBC
      measurements were analysed in a 24 h time bin. An accuracy of 0.73 and
      discriminability of 0.73 AUC for mortality prediction in patients with sepsis was
      achieved with only three features: median of lactate levels, mean arterial
      pressure, and median absolute deviation of the respiratory rate. DISCUSSION: This
      study introduces a new scheme for the prediction of lactate levels and mortality
      risk from patient vital signs and WBC. Accurate prediction of both these
      variables can drive the appropriate response by clinical staff and thus may have
      important implications for patient health and treatment outcome. CONCLUSIONS:
      Effective predictions of lactate levels and mortality risk can be provided with a
      few clinical variables when the temporal aspect and variability of patient data
      are considered.

PMID- 23959844
TI  - Pathology imaging informatics for quantitative analysis of whole-slide images.
AB  - OBJECTIVES: With the objective of bringing clinical decision support systems to
      reality, this article reviews histopathological whole-slide imaging informatics
      methods, associated challenges, and future research opportunities. TARGET
      AUDIENCE: This review targets pathologists and informaticians who have a limited
      understanding of the key aspects of whole-slide image (WSI) analysis and/or a
      limited knowledge of state-of-the-art technologies and analysis methods. SCOPE:
      First, we discuss the importance of imaging informatics in pathology and
      highlight the challenges posed by histopathological WSI. Next, we provide a
      thorough review of current methods for: quality control of histopathological
      images; feature extraction that captures image properties at the pixel, object,
      and semantic levels; predictive modeling that utilizes image features for
      diagnostic or prognostic applications; and data and information visualization
      that explores WSI for de novo discovery. In addition, we highlight future
      research directions and discuss the impact of large public repositories of
      histopathological data, such as the Cancer Genome Atlas, on the field of
      pathology informatics. Following the review, we present a case study to
      illustrate a clinical decision support system that begins with quality control
      and ends with predictive modeling for several cancer endpoints. Currently, state
      of-the-art software tools only provide limited image processing capabilities
      instead of complete data analysis for clinical decision-making. We aim to inspire
      researchers to conduct more research in pathology imaging informatics so that
      clinical decision support can become a reality.

PMID- 23959847
TI  - Epicardial mapping and ablation of arrhythmias: is magnetic navigation the answer
      we have been waiting for?

PMID- 23959846
TI  - Possible HIV transmission modes among at-risk groups at an early epidemic stage
      in the Philippines.
AB  - A concentrated human immunodeficiency virus (HIV) epidemic might have started in
      the Philippines. A subsequent characterization of viruses was carried out to
      estimate HIV transmission modes. Most HIV strains from injecting drug users
      belonged to subtype-B. CRF-01 was a major subtype harbored by three other at-risk
      populations: male visa applicants who had sex with men, "men who have sex with
      men," and visa applicants. An HIV phylogeny suggested that two strain groups of
      injecting drug users and others circulated separately. In contrast, there was
      substantial genetic overlap between two strain groups from "men who have sex with
      men" and visa applicants. Mean nucleotide distance within strains was shorter
      among subtype-B strains harbored by the injecting drug users (0.010) than among
      CRF-01 strains of the other three populations: male visa applicants who had sex
      with men (0.034), "men who have sex with men" (0.023), and visa applicants
      (0.032). Closely related strains of hepatitis C virus were derived from not only
      HIV-positive but also -negative individuals. These results suggest that there is
      potential for transmission from visa applicants to "men who have sex with men,"
      and that once HIV occurs in injecting drug users, it spreads rapidly among them.
      Close contacts of hepatitis C virus carriers composed of HIV-negative and 
      positive individuals indicated ongoing HIV spread via blood and possible
      intervention points. Large-scale analysis is needed to provide more precise
      information on the transmission directions and to help curb the growth of this
      HIV epidemic in the Philippines.

PMID- 23959845
TI  - Eliminative signaling by Janus kinases: role in the downregulation of associated
      receptors.
AB  - Activation of cytokine receptor-associated Janus kinases (JAKs) mediates most, if
      not all, of the cellular responses to peptide hormones and cytokines.
      Consequently, JAKs play a paramount role in homeostasis and immunity. Members of
      this family of tyrosine kinases control the cytokine/hormone-induced alterations
      in cell gene expression program. This function is largely mediated through an
      ability to signal toward activation of the signal transducer and activator of
      transcription proteins (STAT), as well as toward some other pathways.
      Importantly, JAKs are also instrumental in tightly controlling the expression of
      associated cytokine and hormone receptors, and, accordingly, in regulating the
      cell sensitivity to these cytokines and hormones. This review highlights the
      enzymatic and non-enzymatic mechanisms of this regulation and discusses the
      importance of the ambidextrous nature of JAK as a key signaling node that
      integrates the combining functions of forward signaling and eliminative
      signaling. Attention to the latter aspect of JAK function may contribute to
      emancipating our approaches to the pharmacological modulation of JAKs.

PMID- 23959848
TI  - The role of exercise echocardiography in the management of mitral valve disease.
AB  - PURPOSE: Exercise echocardiography can assess the dynamic component of mitral
      valve (MV) disease and may therefore be helpful for the clinical decision-making
      by the heart team. The purpose of this study is to determine the role of exercise
      echocardiography in the management of disproportionately symptomatic or otherwise
      atypical patients with mitral regurgitation (MR) and stenosis (MS) in clinical
      practice. METHODS: Data of 14 MR and 14 MS patients, including echocardiograms at
      rest, were presented retrospectively to an experienced heart team to determine
      treatment strategy. Subsequently, exercise echo data were provided whereupon once
      again the treatment strategy was determined. This resulted in: value of exercise
      echo by means of 1) alteration or 2) confirmation of treatment strategy or 3) no
      additional value. RESULTS: During exercise the echocardiographic severity of MV
      disease increased in 9 (64 %) MR and 8 (57 %) MS patients. Based upon alteration
      or confirmation of the treatment strategy, the value of exercise echocardiography
      in the management of MR and MS was 86 % and 57 %, respectively. CONCLUSION: This
      study showed that physical exercise echo can have an important role in the
      clinical decision-making of challenging patients with MV disease. Exercise
      echocardiography had additional value to the treatment strategy in 71 % of these
      patients.

PMID- 23959849
TI  - Computed tomographic imaging in planning redo cardiac surgery after coronary
      bypass grafting - a roadmap to safety.

PMID- 23959850
TI  - The aetiology of myocardial injury after non-cardiac surgery.
AB  - Recognition of myocardial injury after non-cardiac surgery is difficult, since
      strong analgesics (e.g. opioids) can mask anginal symptoms, and ECG abnormalities
      are subtle or transient. Thorough knowledge of the pathophysiological mechanisms
      is therefore essential. These mechanisms can be subdivided into four groups: type
      I myocardial infraction (MI), type II MI, non-ischaemic cardiac pathology, and
      non-cardiac pathology. The incidence of type I MI in patients with a clinical
      suspicion of perioperative acute coronary syndrome (ACS) is 45-57 %. This
      percentage is higher in patients with a high likelihood of MI such as patients
      with ST-elevation ACS. Of note, the generalisability of this statement is limited
      due to significant study limitations. Non-ischaemic cardiac pathology and non
      cardiac pathology should not be overlooked as a cause of perioperative myocardial
      injury (PMI). Especially pulmonary embolism and dysrhythmias are a common
      phenomenon, and may convey important prognostic value. Implementation of routine
      postoperative troponin assessment and accessible use of minimally invasive
      imaging should be considered to provide adequate individualised therapy. Also,
      addition of preoperative imaging may improve the stratification of high-risk
      patients who may benefit from preoperative or perioperative interventions.

PMID- 23959852
TI  - Compartmental models for apical efflux by P-glycoprotein: part 2--a theoretical
      study on transporter kinetic parameters.
AB  - PURPOSE: The impact of efflux transporters in intracellular concentrations of a
      drug can be predicted with modeling techniques. In Part 1, several compartmental
      models were developed and evaluated. The goal of Part 2 was to apply these models
      to the characterization and interpretation of saturation kinetic data. METHODS:
      The compartmental models from Part 1 were used to evaluate a previously published
      dataset from cell lines expressing varying levels of P-glycoprotein. Kinetic
      parameters for the transporter were estimated and compared across models.
      RESULTS: Fits and errors for all compartmental models were identical. All
      compartmental models predicted more consistent parameters than the Michaelis
      Menten model. The 5-compartment model with efflux out of the membrane predicted
      differential impact of P-gp upon apical versus basolateral drug exposure.
      Finally, the saturable kinetics of active efflux along with a permeability
      barrier was modeled to delineate a relationship between intracellular
      concentration with or without active efflux versus donor concentration. This
      relationship was not a rectangular hyperbola, but instead was shown to be a
      quadratic function. CONCLUSIONS: One approach to estimate an in vivo transporter
      effect is to first model an intracellular Km value from in vitro data, and use
      this value along with the appropriate tissue transporter expression levels and
      relative surface area to calculate the relevant apparent Km (or Ki) values.
      Together with the results from Part 1, these studies suggest that compartmental
      models can provide a path forward to better utilize in vitro transporter data for
      in vivo predictions such as physiologically based pharmacokinetic modeling.

PMID- 23959851
TI  - Nanotechnology-based drug delivery systems for targeting, imaging and diagnosis
      of neurodegenerative diseases.
AB  - Neurodegenerative disorders are becoming prevalent with the increasing age of the
      general population. A number of difficulties have emerged for the potential
      treatment of neurodegenerative diseases, as these disorders may be multi systemic
      in nature. Due to limitations regarding the blood brain barrier (BBB) structure,
      efflux pumps and metabolic enzyme expression, conventional drug delivery systems
      do not provide efficient therapy for neurodegenerative disorders. Nanotechnology
      can offer impressive improvement of the neurodegenerative disease treatment by
      using bio-engineered systems interacting with biological systems at a molecular
      level. This review focuses on the nano-enabled system applications for the
      treatment and diagnosis of neurodegenerative diseases, in particular Alzheimer's,
      Parkinson's and Prion diseases.

PMID- 23959853
TI  - In vivo absorption and disposition of cefadroxil after escalating oral doses in
      wild-type and PepT1 knockout mice.
AB  - PURPOSE: To determine the effect of PepT1 on the absorption and disposition of
      cefadroxil, including the potential for saturable intestinal uptake, after
      escalating oral doses of drug. METHODS: The absorption and disposition kinetics
      of [3H]cefadroxil were determined in wild-type and PepT1 knockout mice after
      44.5, 89.1, 178, and 356 nmol/g oral doses of drug. The pharmacokinetics of
      [3H]cefadroxil were also determined in both genotypes after 44.5 nmol/g
      intravenous bolus doses. RESULTS: PepT1 deletion reduced the area under the
      plasma concentration-time profile (AUC0-120) of cefadroxil by 10-fold, the
      maximum plasma concentration (Cmax) by 17.5-fold, and increased the time to reach
      a maximum plasma concentration (Tmax) by 3-fold. There was no evidence of
      nonlinear intestinal absorption since AUC0-120 and Cmax values changed in a dose
      proportional manner. Moreover, the pharmacokinetics of cefadroxil were not
      different between genotypes after intravenous bolus doses, indicating that PepT1
      did not affect drug disposition. Finally, no differences were observed in the
      peripheral tissue distribution of cefadroxil (i.e., outside gastrointestinal
      tract) once these tissues were corrected for differences in perfusing blood
      concentrations. CONCLUSIONS: The findings demonstrate convincingly the critical
      role of intestinal PepT1 in both the rate and extent of oral administration for
      cefadroxil and potentially other aminocephalosporin drugs.

PMID- 23959854
TI  - Lysozyme release and polymer erosion behavior of injectable implants prepared
      from PLGA-PEG block copolymers and PLGA/PLGA-PEG blends.
AB  - PURPOSE: We evaluated the controlled release of lysozyme from various poly(D,L
      lactic-co-glycolic acid) (PLGA) 50/50-polyethylene glycol (PEG) block copolymers
      relative to PLGA 50/50. METHODS: Lysozyme was encapsulated in cylindrical
      implants (0.8 mm diameter) by a solvent extrusion method. Release studies were
      conducted in phosphate buffered saline +0.02% Tween 80 (PBST) at 37 degrees C.
      Lysozyme activity was measured by a fluorescence-based assay. Implant erosion was
      evaluated by kinetics of polymer molecular weight decline, water uptake, and mass
      loss. RESULTS: Lysozyme release from an AB15 di-block copolymer (15% 5 kDa PEG,
      PLGA 28 kDa) was very fast, whereas an AB10 di-block copolymer (with 10% 5 kDa
      PEG, PLGA 45 kDa) and ABA10 tri-block copolymer (with 10% 6 kDa PEG, PLGA 27 kDa)
      showed release profiles similar to PLGA. We achieved continuous lysozyme release
      for up to 4 weeks from AB10 and ABA10 by lysozyme co-encapsulation with the pore
      forming and acid-neutralizing MgCO3, and from AB15 by co-encapsulation of MgCO3
      and blending AB15 with PLGA. Lysozyme activity was mostly recovered during 4
      weeks. CONCLUSIONS: These block co-polymers may have utility either alone or as
      PLGA blends for the controlled release of proteins.

PMID- 23959855
TI  - Specific recruitment of gammadelta regulatory T cells in human breast cancer.
AB  - Understanding the role of different subtypes of tumor-infiltrating lymphocytes
      (TIL) in the immunosuppressive tumor microenvironment is essential for improving
      cancer treatment. Enriched gammadelta1 T-cell populations in TILs suppress T-cell
      responses and dendritic cell maturation in breast cancer, where their presence is
      correlated negatively with clinical outcomes. However, mechanism(s) that explain
      the increase in this class of regulatory T cells (gammadelta Treg) in patients
      with breast cancer have yet to be elucidated. In this study, we show that IP-10
      secreted by breast cancer cells attracted gammadelta Tregs. Using neutralizing
      antibodies against chemokines secreted by breast cancer cells, we found that IP
      10 was the only functional chemokine that causes gammadelta Tregs to migrate
      toward breast cancer cells. In a humanized NOD-scid IL-2Rgamma(null) (NSG) mouse
      model, human breast cancer cells attracted gammadelta Tregs as revealed by a live
      cell imaging system. IP-10 neutralization in vivo inhibited migration and
      trafficking of gammadelta Tregs into breast tumor sites, enhancing tumor immunity
      mediated by tumor-specific T cells. Together, our studies show how gammadelta
      Tregs accumulate in breast tumors, providing a rationale for their immunologic
      targeting to relieve immunosuppression in the tumor microenvironment.

PMID- 23959856
TI  - Tumor cells upregulate normoxic HIF-1alpha in response to doxorubicin.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor that controls
      cellular homeostasis. Although its activation benefits normal tissue, HIF-1
      activation in tumors is a major risk factor for angiogenesis, therapeutic
      resistance, and poor prognosis. HIF-1 activity is usually suppressed under
      normoxic conditions because of rapid oxygen-dependent degradation of HIF-1alpha.
      Here, we show that, under normoxic conditions, HIF-1alpha is upregulated in tumor
      cells in response to doxorubicin, a chemotherapeutic agent used to treat many
      cancers. In addition, doxorubicin enhanced VEGF secretion by normoxic tumor cells
      and stimulated tumor angiogenesis. Doxorubicin-induced accumulation of HIF-1alpha
      in normoxic cells was caused by increased expression and activation of STAT1, the
      activation of which stimulated expression of iNOS and its synthesis of nitric
      oxide (NO) in tumor cells. Mechanistic investigations established that blocking
      NO synthesis or STAT1 activation was sufficient to attenuate the HIF-1alpha
      accumulation induced by doxorubicin in normoxic cancer cells. To our knowledge,
      this is the first report that a chemotherapeutic drug can induce HIF-1alpha
      accumulation in normoxic cells, an efficacy-limiting activity. Our results argue
      that HIF-1alpha-targeting strategies may enhance doxorubicin efficacy. More
      generally, they suggest a broader perspective on the design of combination
      chemotherapy approaches with immediate clinical impact.

PMID- 23959857
TI  - Obesity promotes breast cancer by CCL2-mediated macrophage recruitment and
      angiogenesis.
AB  - Obesity is one of the most important preventable causes of cancer and the most
      significant risk factor for breast cancer in postmenopausal women. Compared with
      lean women, obese women are more likely to be diagnosed with a larger, higher
      grade tumor, an increased incidence of lymph node metastases, and elevated risk
      of distant recurrence. However, the mechanisms connecting obesity to the
      pathogenesis of breast cancer are poorly defined. Here, we show that during
      obesity, adipocytes within human and mouse breast tissues recruit and activate
      macrophages through a previously uncharacterized CCL2/IL-1beta/CXCL12 signaling
      pathway. Activated macrophages in turn promote stromal vascularization and
      angiogenesis even before the formation of cancer. Recapitulating these changes
      using a novel humanized breast cancer model was sufficient to promote
      angiogenesis and prime the microenvironment prior to neoplastic transformation
      for accelerated breast oncogenesis. These findings provide a mechanistic role for
      adipocytes and macrophages before carcinogenesis that may be critical for
      prevention and treatment of obesity-related cancer.

PMID- 23959858
TI  - Poly(ethylene) glycol-capped silver and magnetic nanoparticles: synthesis,
      characterization, and comparison of bactericidal and cytotoxic effects.
AB  - Silver and magnetic (Fe3O4) nanoparticles have attracted wide attention as novel
      antimicrobial agents due to their unique chemical and physical properties. In
      order to study the comparative effects on antibacterial and animal cytotoxicity,
      Staphylococcus aureus and NIH 3T3 fibroblasts were used, respectively. Both
      nanoparticles were synthesized via a novel matrix-mediated method using
      poly(ethylene) glycol. Formation of silver nanoparticles was confirmed by
      fluorescence and ultraviolet-visible spectroscopic techniques. The poly(ethylene)
      glycol-coated silver and Fe3O4 nanoparticles were characterized by scanning
      electron microscope, transmission electron microscope, zeta potential, particle
      size analysis, Fourier-transform infrared, X-ray diffraction, and X-ray
      photoelectron spectroscopy. The antimicrobial results indicate that both
      poly(ethylene) glycol-coated silver and Fe3O4 nanoparticles inhibited S. aureus
      growth at the concentrations of 5 and 10 ug/mL at all time points without showing
      any significant cytotoxicity on NIH 3T3 fibroblasts. The particle size of both
      the poly(ethylene) glycol-coated silver and Fe3O4 nanoparticles dominated in the
      range 10-15 nm, obtained by particle size analyzer. The poly(ethylene) glycol
      coating on the particles showed less aggregation of nanoparticles, as observed by
      scanning electron microscope and transmission electron microscope. The overall
      obtained results indicated that these two nanoparticles were stable and could be
      used to develop a magnetized antimicrobial scaffolds for biomedical applications.

PMID- 23959859
TI  - A bounded iterative closest point method for minimally invasive registration of
      the femur.
AB  - This article describes a novel method for image-based, minimally invasive
      registration of the femur, for application to computer-assisted unicompartmental
      knee arthroplasty. The method is adapted from the well-known iterative closest
      point algorithm. By utilising an estimate of the hip centre on both the
      preoperative model and intraoperative patient anatomy, the proposed 'bounded'
      iterative closest point algorithm robustly produces accurate varus-valgus and
      anterior-posterior femoral alignment with minimal distal access requirements.
      Similar to the original iterative closest point implementation, the bounded
      iterative closest point algorithm converges monotonically to the closest minimum,
      and the presented case includes a common method for global minimum
      identification. The bounded iterative closest point method has shown to have
      exceptional resistance to noise during feature acquisition through simulations
      and in vitro plastic bone trials, where its performance is compared to a standard
      form of the iterative closest point algorithm. 

PMID- 23959860
TI  - Transcriptional response to stress in the dynamic chromatin environment of
      cycling and mitotic cells.
AB  - Heat shock factors (HSFs) are the master regulators of transcription under
      protein-damaging conditions, acting in an environment where the overall
      transcription is silenced. We determined the genomewide transcriptional program
      that is rapidly provoked by HSF1 and HSF2 under acute stress in human cells. Our
      results revealed the molecular mechanisms that maintain cellular homeostasis,
      including HSF1-driven induction of polyubiquitin genes, as well as HSF1- and HSF2
      mediated expression patterns of cochaperones, transcriptional regulators, and
      signaling molecules. We characterized the genomewide transcriptional response to
      stress also in mitotic cells where the chromatin is tightly compacted. We found a
      radically limited binding and transactivating capacity of HSF1, leaving mitotic
      cells highly susceptible to proteotoxicity. In contrast, HSF2 occupied hundreds
      of loci in the mitotic cells and localized to the condensed chromatin also in
      meiosis. These results highlight the importance of the cell cycle phase in
      transcriptional responses and identify the specific mechanisms for HSF1 and HSF2
      in transcriptional orchestration. Moreover, we propose that HSF2 is an epigenetic
      regulator directing transcription throughout cell cycle progression. 

PMID- 23959862
TI  - QnAs with Daniel Kahneman.

PMID- 23959861
TI  - Treatment with suboptimal doses of raltegravir leads to aberrant HIV-1
      integrations.
AB  - Integration of the DNA copy of the HIV-1 genome into a host chromosome is
      required for viral replication and is thus an important target for antiviral
      therapy. The HIV-encoded enzyme integrase (IN) catalyzes two essential steps: 3'
      processing of the viral DNA ends, followed by the strand transfer reaction, which
      inserts the viral DNA into host DNA. Raltegravir binds to IN and blocks the
      integration of the viral DNA. Using the Rous sarcoma virus-derived vector RCAS,
      we previously showed that mutations that cause one viral DNA end to be defective
      for IN-mediated integration led to abnormal integrations in which the provirus
      had one normal and one aberrant end, accompanied by rearrangements in the host
      genome. On the basis of these results, we expected that suboptimal concentrations
      of IN inhibitors, which could block one of the ends of viral integration, would
      lead to similar aberrant integrations. In contrast to the proviruses from
      untreated cells, which were all normal, ~10-15% of the proviruses isolated after
      treatment with a suboptimal dose of raltegravir were aberrant. The aberrant
      integrations were similar to those seen in the RCAS experiments. Most of the
      aberrant proviruses had one normal end and one aberrant end and were accompanied
      by significant rearrangements in the host genome, including duplications,
      inversions, deletions and, occasionally, acquisition of sequences from other
      chromosomes. The rearrangements of the host DNA raise concerns that these
      aberrant integrations might have unintended consequences in HIV-1-infected
      patients who are not consistent in following a raltegravir-containing treatment
      regimen. 

PMID- 23959863
TI  - Implications for the evolution of eukaryotic amino-terminal acetyltransferase
      (NAT) enzymes from the structure of an archaeal ortholog.
AB  - Amino-terminal acetylation is a ubiquitous modification in eukaryotes that is
      involved in a growing number of biological processes. There are six known
      eukaryotic amino-terminal acetyltransferases (NATs), which are differentiated
      from one another on the basis of substrate specificity. To date, two eukaryotic
      NATs, NatA and NatE, have been structurally characterized, of which NatA will
      acetylate the alpha-amino group of a number of nonmethionine amino-terminal
      residue substrates such as serine; NatE requires a substrate amino-terminal
      methionine residue for activity. Interestingly, these two NATs use different
      catalytic strategies to accomplish substrate-specific acetylation. In archaea,
      where this modification is less prevalent, only one NAT enzyme has been
      identified. Surprisingly, this enzyme is able to acetylate NatA and NatE
      substrates and is believed to represent an ancestral NAT variant from which the
      eukaryotic NAT machinery evolved. To gain insight into the evolution of NAT
      enzymes, we determined the X-ray crystal structure of an archaeal NAT from
      Sulfolobus solfataricus (ssNAT). Through the use of mutagenesis and kinetic
      analysis, we show that the active site of ssNAT represents a hybrid of the NatA
      and NatE active sites, and we highlight features of this protein that allow it to
      facilitate catalysis of distinct substrates through different catalytic
      strategies, which is a unique characteristic of this enzyme. Taken together, the
      structural and biochemical data presented here have implications for the
      evolution of eukaryotic NAT enzymes and the substrate specificities therein. 

PMID- 23959864
TI  - Gene duplication in the major insecticide target site, Rdl, in Drosophila
      melanogaster.
AB  - The Resistance to Dieldrin gene, Rdl, encodes a GABA-gated chloride channel
      subunit that is targeted by cyclodiene and phenylpyrazole insecticides. The gene
      was first characterized in Drosophila melanogaster by genetic mapping of
      resistance to the cyclodiene dieldrin. The 4,000-fold resistance observed was due
      to a single amino acid replacement, Ala(301) to Ser. The equivalent change was
      subsequently identified in Rdl orthologs of a large range of resistant insect
      species. Here, we report identification of a duplication at the Rdl locus in D.
      melanogaster. The 113-kb duplication contains one WT copy of Rdl and a second
      copy with two point mutations: an Ala(301) to Ser resistance mutation and
      Met(360) to Ile replacement. Individuals with this duplication exhibit
      intermediate dieldrin resistance compared with single copy Ser(301) homozygotes,
      reduced temperature sensitivity, and altered RNA editing associated with the
      resistant allele. Ectopic recombination between Roo transposable elements is
      involved in generating this genomic rearrangement. The duplication phenotypes
      were confirmed by construction of a transgenic, artificial duplication
      integrating the 55.7-kb Rdl locus with a Ser(301) change into an Ala(301)
      background. Gene duplications can contribute significantly to the evolution of
      insecticide resistance, most commonly by increasing the amount of gene product
      produced. Here however, duplication of the Rdl target site creates permanent
      heterozygosity, providing unique potential for adaptive mutations to accrue in
      one copy, without abolishing the endogenous role of an essential gene. 

PMID- 23959865
TI  - Establishing a hematopoietic genetic network through locus-specific integration
      of chromatin regulators.
AB  - The establishment and maintenance of cell type-specific transcriptional programs
      require an ensemble of broadly expressed chromatin remodeling and modifying
      enzymes. Many questions remain unanswered regarding the contributions of these
      enzymes to specialized genetic networks that control critical processes, such as
      lineage commitment and cellular differentiation. We have been addressing this
      problem in the context of erythrocyte development driven by the transcription
      factor GATA-1 and its coregulator Friend of GATA-1 (FOG-1). As certain GATA-1
      target genes have little to no FOG-1 requirement for expression, presumably
      additional coregulators can mediate GATA-1 function. Using a genetic
      complementation assay and RNA interference in GATA-1-null cells, we demonstrate a
      vital link between GATA-1 and the histone H4 lysine 20 methyltransferase PR
      Set7/SetD8 (SetD8). GATA-1 selectively induced H4 monomethylated lysine 20 at
      repressed, but not activated, loci, and endogenous SetD8 mediated GATA-1
      dependent repression of a cohort of its target genes. GATA-1 used different
      combinations of SetD8, FOG-1, and the FOG-1-interacting nucleosome remodeling and
      deacetylase complex component Mi2beta to repress distinct target genes.
      Implicating SetD8 as a context-dependent GATA-1 corepressor expands the
      repertoire of coregulators mediating establishment/maintenance of the erythroid
      cell genetic network, and provides a biological framework for dissecting the cell
      type-specific functions of this important coregulator. We propose a coregulator
      matrix model in which distinct combinations of chromatin regulators are required
      at different GATA-1 target genes, and the unique attributes of the target loci
      mandate these combinations. 

PMID- 23959866
TI  - PINK1 regulates histone H3 trimethylation and gene expression by interaction with
      the polycomb protein EED/WAIT1.
AB  - Mutations in PTEN-induced putative kinase 1 (PINK1) gene are associated to early
      onset recessive forms of Parkinson disease. PINK1 function is related to
      mitochondria homeostasis, but the molecular pathways in which PINK1 is involved
      are largely unknown. Here, we report the identification of the embryonic ectoderm
      development polycomb histone-methylation modulator (EED/WAIT1) as a PINK1
      interacting and -regulated protein. The PINK1:EED/WAIT1 physical interaction was
      mediated by the PINK1 kinase domain and the EED/WAIT1 40 amino acid ending with
      tryptophan and aspartate (WD40)-repeat region, and PINK1 phosphorylated EED/WAIT1
      in vitro. PINK1 associated with EED/WAIT1 in cells and relocated EED/WAIT1 to the
      mitochondria. This interaction reduced the trimethylation of lysine 27 from
      histone H3, which affected polycomb-regulated gene transcription during RA
      differentiation of SH-SY5Y human neuroblastoma cells. Our findings unveil a
      pathway by which PINK1 regulates histone methylation and gene expression through
      the polycomb repressor complex. 

PMID- 23959867
TI  - Insights into Eph receptor tyrosine kinase activation from crystal structures of
      the EphA4 ectodomain and its complex with ephrin-A5.
AB  - Eph receptor tyrosine kinases and their ephrin ligands mediate cell signaling
      during normal and oncogenic development. Eph signaling is initiated in a
      multistep process leading to the assembly of higher-order Eph/ephrin clusters
      that set off bidirectional signaling in interacting cells. Eph and ephrins are
      divided in two subclasses based on their abilities to bind and activate each
      other and on sequence conservation. EphA4 is an exception to the general rule
      because it can be activated by both A- and B-class ephrin ligands. Here we
      present high-resolution structures of the complete EphA4 ectodomain and its
      complexes with ephrin-A5. The structures reveal how ligand binding promotes
      conformational changes in the EphA4 ligand-binding domain allowing the formation
      of signaling clusters at the sites of cell-cell contact. In addition, the
      structural data, combined with structure-based mutagenesis, reveal a previously
      undescribed receptor-receptor interaction between the EphA4 ligand-binding and
      membrane-proximal fibronectin domains, which is functionally important for
      efficient receptor activation. 

PMID- 23959868
TI  - Population-genomic insights into the evolutionary origin and fate of obligately
      asexual Daphnia pulex.
AB  - Despite much theoretical work, the molecular-genetic causes and evolutionary
      consequences of asexuality remain largely undetermined. Asexual animal species
      are rare, evolutionarily short-lived, and thought to suffer mutational meltdown
      as a result of lack of recombination. Whole-genome analysis of 11 sexual and 11
      asexual genotypes of Daphnia pulex indicates that current asexual lineages are in
      fact very young, exhibit no signs of purifying selection against accumulating
      mutations, and have extremely high rates of gene conversion and deletion. The
      reconstruction of chromosomal haplotypes in regions containing SNP markers
      associated with asexuality (chromosomes VIII and IX) indicates that introgression
      from a sister species, Daphnia pulicaria, underlies the origin of the asexual
      phenotype. Silent-site divergence of the shared chromosomal haplotypes of
      asexuals indicates that the spread of asexuality is as recent as 1,250 y,
      although the origin of the meiosis-suppressing element or elements could be
      substantially older. In addition, using previous estimates of the gene conversion
      rate from Daphnia mutation accumulation lines, we are able to age each asexual
      lineage. Although asexual lineages originate from wide crosses that introduce
      elevated individual heterozygosities on clone foundation, they also appear to be
      constrained by the inbreeding-like effect of loss of heterozygosity that accrues
      as gene conversion and hemizygous deletion expose preexisting recessive
      deleterious alleles of asexuals, limiting their evolutionary longevity. Our study
      implies that the buildup of newly introduced deleterious mutations (i.e.,
      Muller's ratchet) may not be the dominant force imperiling nonrecombining
      populations of D. pulex, as previously proposed. 

PMID- 23959869
TI  - Ontogeny of prosocial behavior across diverse societies.
AB  - Humans are an exceptionally cooperative species, but there is substantial
      variation in the extent of cooperation across societies. Understanding the
      sources of this variability may provide insights about the forces that sustain
      cooperation. We examined the ontogeny of prosocial behavior by studying 326
      children 3-14 y of age and 120 adults from six societies (age distributions
      varied across societies). These six societies span a wide range of extant human
      variation in culture, geography, and subsistence strategies, including foragers,
      herders, horticulturalists, and urban dwellers across the Americas, Oceania, and
      Africa. When delivering benefits to others was personally costly, rates of
      prosocial behavior dropped across all six societies as children approached middle
      childhood and then rates of prosociality diverged as children tracked toward the
      behavior of adults in their own societies. When prosocial acts did not require
      personal sacrifice, prosocial responses increased steadily as children matured
      with little variation in behavior across societies. Our results are consistent
      with theories emphasizing the importance of acquired cultural norms in shaping
      costly forms of cooperation and creating cross-cultural diversity. 

PMID- 23959870
TI  - Low levels of copper disrupt brain amyloid-beta homeostasis by altering its
      production and clearance.
AB  - Whereas amyloid-beta (Abeta) accumulates in the brain of normal animals dosed
      with low levels of copper (Cu), the mechanism is not completely known. Cu could
      contribute to Abeta accumulation by altering its clearance and/or its production.
      Because Cu homeostasis is altered in transgenic mice overexpressing Abeta
      precursor protein (APP), the objective of this study was to elucidate the
      mechanism of Cu-induced Abeta accumulation in brains of normal mice and then to
      explore Cu's effects in a mouse model of Alzheimer's disease. In aging mice,
      accumulation of Cu in brain capillaries was associated with its reduction in low
      density lipoprotein receptor-related protein 1 (LRP1), an Abeta transporter, and
      higher brain Abeta levels. These effects were reproduced by chronic dosing with
      low levels of Cu via drinking water without changes in Abeta synthesis or
      degradation. In human brain endothelial cells, Cu, at its normal labile levels,
      caused LRP1-specific down-regulation by inducing its nitrotyrosination and
      subsequent proteosomal-dependent degradation due in part to Cu/cellular prion
      protein/LRP1 interaction. In APP(sw/0) mice, Cu not only down-regulated LRP1 in
      brain capillaries but also increased Abeta production and neuroinflammation
      because Cu accumulated in brain capillaries and, unlike in control mice, in the
      parenchyma. Thus, we have demonstrated that Cu's effect on brain Abeta
      homeostasis depends on whether it is accumulated in the capillaries or in the
      parenchyma. These findings should provide unique insights into preventative
      and/or therapeutic approaches to control neurotoxic Abeta levels in the aging
      brain. 

PMID- 23959871
TI  - Environmental productivity predicts migration, demographic, and linguistic
      patterns in prehistoric California.
AB  - Global patterns of ethnolinguistic diversity vary tremendously. Some regions show
      very little variation even across vast expanses, whereas others exhibit dense
      mosaics of different languages spoken alongside one another. Compared with the
      rest of Native North America, prehistoric California exemplified the latter.
      Decades of linguistic, genetic, and archaeological research have produced
      detailed accounts of the migrations that aggregated to build California's diverse
      ethnolinguistic mosaic, but there have been few have attempts to explain the
      process underpinning these migrations and why such a mosaic did not develop
      elsewhere. Here we show that environmental productivity predicts both the order
      of migration events and the population density recorded at contact. The earliest
      colonizers occupied the most suitable habitats along the coast, whereas
      subsequent Mid-Late Holocene migrants settled in more marginal habitats. Other
      Late Holocene patterns diverge from this trend, reflecting altered dynamics
      linked to food storage and increased sedentism. Through repeated migration
      events, incoming populations replaced resident populations occurring at lower
      densities in lower-productivity habitats, thereby resulting in the fragmentation
      of earlier groups and the development of one of the most diverse ethnolinguistic
      patterns in the Americas. Such a process may account for the distribution of
      ethnolinguistic diversity worldwide. 

PMID- 23959872
TI  - Design and characterization of synthetic fungal-bacterial consortia for direct
      production of isobutanol from cellulosic biomass.
AB  - Synergistic microbial communities are ubiquitous in nature and exhibit appealing
      features, such as sophisticated metabolic capabilities and robustness. This has
      inspired fast-growing interest in engineering synthetic microbial consortia for
      biotechnology development. However, there are relatively few reports of their use
      in real-world applications, and achieving population stability and regulation has
      proven to be challenging. In this work, we bridge ecology theory with engineering
      principles to develop robust synthetic fungal-bacterial consortia for efficient
      biosynthesis of valuable products from lignocellulosic feedstocks. The required
      biological functions are divided between two specialists: the fungus Trichoderma
      reesei, which secretes cellulase enzymes to hydrolyze lignocellulosic biomass
      into soluble saccharides, and the bacterium Escherichia coli, which metabolizes
      soluble saccharides into desired products. We developed and experimentally
      validated a comprehensive mathematical model for T. reesei/E. coli consortia,
      providing insights on key determinants of the system's performance. To illustrate
      the bioprocessing potential of this consortium, we demonstrate direct conversion
      of microcrystalline cellulose and pretreated corn stover to isobutanol. Without
      costly nutrient supplementation, we achieved titers up to 1.88 g/L and yields up
      to 62% of theoretical maximum. In addition, we show that cooperator-cheater
      dynamics within T. reesei/E. coli consortia lead to stable population equilibria
      and provide a mechanism for tuning composition. Although we offer isobutanol
      production as a proof-of-concept application, our modular system could be readily
      adapted for production of many other valuable biochemicals. 

PMID- 23959873
TI  - Two-state dynamics of the SH3-SH2 tandem of Abl kinase and the allosteric role of
      the N-cap.
AB  - The regulation and localization of signaling enzymes is often mediated by
      accessory modular domains, which frequently function in tandems. The ability of
      these tandems to adopt multiple conformations is as important for proper
      regulation as the individual domain specificity. A paradigmatic example is Abl, a
      ubiquitous tyrosine kinase of significant pharmacological interest. SH3 and SH2
      domains inhibit Abl by assembling onto the catalytic domain, allosterically
      clamping it in an inactive state. We investigate the dynamics of this SH3-SH2
      tandem, using microsecond all-atom simulations and differential scanning
      calorimetry. Our results indicate that the Abl tandem is a two-state switch,
      alternating between the conformation observed in the structure of the
      autoinhibited enzyme and another configuration that is consistent with existing
      scattering data for an activated form. Intriguingly, we find that the latter is
      the most probable when the tandem is disengaged from the catalytic domain.
      Nevertheless, an amino acid stretch preceding the SH3 domain, the so-called N
      cap, reshapes the free-energy landscape of the tandem and favors the interaction
      of this domain with the SH2-kinase linker, an intermediate step necessary for
      assembly of the autoinhibited complex. This allosteric effect arises from
      interactions between N-cap and the SH2 domain and SH3-SH2 connector, which
      involve a phosphorylation site. We also show that the SH3-SH2 connector plays a
      determinant role in the assembly equilibrium of Abl, because mutations thereof
      hinder the engagement of the SH2-kinase linker. These results provide a
      thermodynamic rationale for the involvement of N-cap and SH3-SH2 connector in Abl
      regulation and expand our understanding of the principles of modular domain
      organization. 

PMID- 23959875
TI  - Profoundly different prion diseases in knock-in mice carrying single PrP codon
      substitutions associated with human diseases.
AB  - In man, mutations in different regions of the prion protein (PrP) are associated
      with infectious neurodegenerative diseases that have remarkably different
      clinical signs and neuropathological lesions. To explore the roots of this
      phenomenon, we created a knock-in mouse model carrying the mutation associated
      with one of these diseases [Creutzfeldt-Jakob disease (CJD)] that was exactly
      analogous to a previous knock-in model of a different prion disease [fatal
      familial insomnia (FFI)]. Together with the WT parent, this created an allelic
      series of three lines, each expressing the same protein with a single amino acid
      difference, and with all native regulatory elements intact. The previously
      described FFI mice develop neuronal loss and intense reactive gliosis in the
      thalamus, as seen in humans with FFI. In contrast, CJD mice had the hallmark
      features of CJD, spongiosis and proteinase K-resistant PrP aggregates, initially
      developing in the hippocampus and cerebellum but absent from the thalamus. A
      molecular transmission barrier protected the mice from any infectious prion
      agents that might have been present in our mouse facility and allowed us to
      conclude that the diseases occurred spontaneously. Importantly, both models
      created agents that caused a transmissible neurodegenerative disease in WT mice.
      We conclude that single codon differences in a single gene in an otherwise normal
      genome can cause remarkably different neurodegenerative diseases and are
      sufficient to create distinct protein-based infectious elements. 

PMID- 23959874
TI  - Protein kinase Cbeta as a therapeutic target stabilizing blood-brain barrier
      disruption in experimental autoimmune encephalomyelitis.
AB  - Disruption of the blood-brain barrier (BBB) is a hallmark of acute inflammatory
      lesions in multiple sclerosis (MS) and its animal model experimental autoimmune
      encephalomyelitis. This disruption may precede and facilitate the infiltration of
      encephalitogenic T cells. The signaling events that lead to this BBB disruption
      are incompletely understood but appear to involve dysregulation of tight-junction
      proteins such as claudins. Pharmacological interventions aiming at stabilizing
      the BBB in MS might have therapeutic potential. Here, we show that the orally
      available small molecule LY-317615, a synthetic bisindolylmaleimide and inhibitor
      of protein kinase Cbeta, which is clinically under investigation for the
      treatment of cancer, suppresses the transmigration of activated T cells through
      an inflamed endothelial cell barrier, where it leads to the induction of the
      tight-junction molecules zona occludens-1, claudin 3, and claudin 5 and other
      pathways critically involved in transendothelial leukocyte migration. Treatment
      of mice with ongoing experimental autoimmune encephalomyelitis with LY-317615
      ameliorates inflammation, demyelination, axonal damage, and clinical symptoms.
      Although LY-317615 dose-dependently suppresses T-cell proliferation and cytokine
      production independent of antigen specificity, its therapeutic effect is
      abrogated in a mouse model requiring pertussis toxin. This abrogation indicates
      that the anti-inflammatory and clinical efficacy is mainly mediated by
      stabilization of the BBB, thus suppressing the transmigration of encephalitogenic
      T cells. Collectively, our data suggest the involvement of endothelial protein
      kinase Cbeta in stabilizing the BBB in autoimmune neuroinflammation and imply a
      therapeutic potential of BBB-targeting agents such as LY-317615 as therapeutic
      approaches for MS. 

PMID- 23959876
TI  - Hypoxic retinal Muller cells promote vascular permeability by HIF-1-dependent up
      regulation of angiopoietin-like 4.
AB  - Vision loss from ischemic retinopathies commonly results from the accumulation of
      fluid in the inner retina [macular edema (ME)]. Although the precise events that
      lead to the development of ME remain under debate, growing evidence supports a
      role for an ischemia-induced hyperpermeability state regulated, in part, by VEGF.
      Monthly treatment with anti-VEGF therapies is effective for the treatment of ME
      but results in a major improvement in vision in a minority of patients,
      underscoring the need to identify additional therapeutic targets. Using the
      oxygen-induced retinopathy mouse model for ischemic retinopathy, we provide
      evidence showing that hypoxic Muller cells promote vascular permeability by
      stabilizing hypoxia-inducible factor-1alpha (HIF-1alpha) and secreting angiogenic
      cytokines. Blocking HIF-1alpha translation with digoxin inhibits the promotion of
      endothelial cell permeability in vitro and retinal edema in vivo. Interestingly,
      Muller cells require HIF--but not VEGF--to promote vascular permeability,
      suggesting that other HIF-dependent factors may contribute to the development of
      ME. Using gene expression analysis, we identify angiopoietin-like 4 (ANGPTL4) as
      a cytokine up-regulated by HIF-1 in hypoxic Muller cells in vitro and the
      ischemic inner retina in vivo. ANGPTL4 is critical and sufficient to promote
      vessel permeability by hypoxic Muller cells. Immunohistochemical analysis of
      retinal tissue from patients with diabetic eye disease shows that HIF-1alpha and
      ANGPTL4 localize to ischemic Muller cells. Our results suggest that ANGPTL4 may
      play an important role in promoting vessel permeability in ischemic retinopathies
      and could be an important target for the treatment of ME.

PMID- 23959877
TI  - Analysis of Chlamydomonas thiamin metabolism in vivo reveals riboswitch
      plasticity.
AB  - Thiamin (vitamin B1) is an essential micronutrient needed as a cofactor for many
      central metabolic enzymes. Animals must have thiamin in their diet, whereas
      bacteria, fungi, and plants can biosynthesize it de novo from the condensation of
      a thiazole and a pyrimidine moiety. Although the routes to biosynthesize these
      two heterocycles are not conserved in different organisms, in all cases exogenous
      thiamin represses expression of one or more of the biosynthetic pathway genes.
      One important mechanism for this control is via thiamin-pyrophosphate (TPP)
      riboswitches, regions of the mRNA to which TPP can bind directly, thus
      facilitating fine-tuning to maintain homeostasis. However, there is little
      information on how modulation of riboswitches affects thiamin metabolism in vivo.
      Here we use the green alga, Chlamydomonas reinhardtii, which regulates both
      thiazole and pyrimidine biosynthesis with riboswitches in the THI4 (Thiamin 4)
      and THIC (Thiamin C) genes, respectively, to investigate this question. Our study
      reveals that regulation of thiamin metabolism is not the simple dogma of negative
      feedback control. Specifically, balancing the provision of both of the
      heterocycles of TPP appears to be an important requirement. Furthermore, we show
      that the Chlamydomonas THIC riboswitch is controlled by hydroxymethylpyrimidine
      pyrophosphate, as well as TPP, but with an identical alternative splicing
      mechanism. Similarly, the THI4 gene is responsive to thiazole. The study not only
      provides insight into the plasticity of the TPP riboswitches but also shows that
      their maintenance is likely to be a consequence of evolutionary need as a
      function of the organisms' environment and the particular pathway used. 

PMID- 23959878
TI  - Human alpha-L-iduronidase uses its own N-glycan as a substrate-binding and
      catalytic module.
AB  - N-glycosylation is a major posttranslational modification that endows proteins
      with various functions. It is established that N-glycans are essential for the
      correct folding and stability of some enzymes; however, the actual effects of N
      glycans on their activities are poorly understood. Here, we show that human alpha
      l-iduronidase (hIDUA), of which a dysfunction causes accumulation of
      dermatan/heparan sulfate leading to mucopolysaccharidosis type I, uses its own N
      glycan as a substrate binding and catalytic module. Structural analysis revealed
      that the mannose residue of the N-glycan attached to N372 constituted a part of
      the substrate-binding pocket and interacted directly with a substrate. A
      deglycosylation study showed that enzyme activity was highly correlated with the
      N-glycan attached to N372. The kinetics of native and deglycosylated hIDUA
      suggested that the N-glycan is also involved in catalytic processes. Our study
      demonstrates a previously unrecognized function of N-glycans. 

PMID- 23959879
TI  - Cotranslational folding of membrane proteins probed by arrest-peptide-mediated
      force measurements.
AB  - Polytopic membrane proteins are inserted cotranslationally into target membranes
      by ribosome-translocon complexes. It is, however, unclear when during the
      insertion process specific interactions between the transmembrane helices start
      to form. Here, we use a recently developed in vivo technique to measure pulling
      forces acting on transmembrane helices during their cotranslational insertion
      into the inner membrane of Escherichia coli to study the earliest steps of
      tertiary folding of five polytopic membrane proteins. We find that interactions
      between residues in a C-terminally located transmembrane helix and in more N
      terminally located helices can be detected already at the point when the C
      terminal helix partitions from the translocon into the membrane. Our findings
      pinpoint the earliest steps of tertiary structure formation and open up
      possibilities to study the cotranslational folding of polytopic membrane
      proteins. 

PMID- 23959880
TI  - Dorsal periaqueductal gray-amygdala pathway conveys both innate and learned fear
      responses in rats.
AB  - The periaqueductal gray (PAG) and amygdala are known to be important for
      defensive responses, and many contemporary fear-conditioning models present the
      PAG as downstream of the amygdala, directing the appropriate behavior (i.e.,
      freezing or fleeing). However, empirical studies of this circuitry are
      inconsistent and warrant further examination. Hence, the present study
      investigated the functional relationship between the PAG and amygdala in two
      different settings, fear conditioning and naturalistic foraging, in rats. In fear
      conditioning, electrical stimulation of the dorsal PAG (dPAG) produced
      unconditional responses (URs) composed of brief activity bursts followed by
      freezing and 22-kHz ultrasonic vocalization. In contrast, stimulation of ventral
      PAG and the basolateral amygdalar complex (BLA) evoked freezing and/or ultrasonic
      vocalization. Whereas dPAG stimulation served as an effective unconditional
      stimulus for fear conditioning to tone and context conditional stimuli, neither
      ventral PAG nor BLA stimulation supported fear conditioning. The conditioning
      effect of dPAG, however, was abolished by inactivation of the BLA. In a foraging
      task, dPAG and BLA stimulation evoked only fleeing toward the nest. Amygdalar
      lesion/inactivation blocked the UR of dPAG stimulation, but dPAG lesions did not
      block the UR of BLA stimulation. Furthermore, in vivo recordings demonstrated
      that electrical priming of the dPAG can modulate plasticity of subiculum-BLA
      synapses, providing additional evidence that the amygdala is downstream of the
      dPAG. These results suggest that the dPAG conveys unconditional stimulus
      information to the BLA, which directs both innate and learned fear responses, and
      that brain stimulation-evoked behaviors are modulated by context. 

PMID- 23959881
TI  - NAF-1 and mitoNEET are central to human breast cancer proliferation by
      maintaining mitochondrial homeostasis and promoting tumor growth.
AB  - Mitochondria are emerging as important players in the transformation process of
      cells, maintaining the biosynthetic and energetic capacities of cancer cells and
      serving as one of the primary sites of apoptosis and autophagy regulation.
      Although several avenues of cancer therapy have focused on mitochondria, progress
      in developing mitochondria-targeting anticancer drugs nonetheless has been slow,
      owing to the limited number of known mitochondrial target proteins that link
      metabolism with autophagy or cell death. Recent studies have demonstrated that
      two members of the newly discovered family of NEET proteins, NAF-1 (CISD2) and
      mitoNEET (mNT; CISD1), could play such a role in cancer cells. NAF-1 was shown to
      be a key player in regulating autophagy, and mNT was proposed to mediate iron and
      reactive oxygen homeostasis in mitochondria. Here we show that the protein levels
      of NAF-1 and mNT are elevated in human epithelial breast cancer cells, and that
      suppressing the level of these proteins using shRNA results in significantly
      reduced cell proliferation and tumor growth, decreased mitochondrial performance,
      uncontrolled accumulation of iron and reactive oxygen in mitochondria, and
      activation of autophagy. Our findings highlight NEET proteins as promising
      mitochondrial targets for cancer therapy. 

PMID- 23959882
TI  - Role of the ectonucleotidase NTPDase2 in taste bud function.
AB  - Taste buds are unusual in requiring ATP as a transmitter to activate sensory
      nerve fibers. In response to taste stimuli, taste cells release ATP, activating
      purinergic receptors containing the P2X2 and P2X3 subunits on taste nerves. In
      turn, the released ATP is hydrolyzed to ADP by a plasma membrane nucleoside
      triphosphate previously identified as nucleoside triphosphate diphosphohydrolase
      2 (NTPDase2). In this paper we investigate the role of this ectonucleotidase in
      the function of taste buds by examining gene-targeted Entpd2-null mice globally
      lacking NTPDase2. RT-PCR confirmed the absence of NTPDase2, and ATPase enzyme
      histochemistry reveals no reaction product in taste buds of knockout mice,
      suggesting that NTPDase2 is the dominant form in taste buds. RT-PCR and
      immunocytochemistry demonstrated that in knockout mice all cell types are present
      in taste buds, even those cells normally expressing NTPDase2. In addition, the
      overall number and size of taste buds are normal in Entpd2-null mice.
      Luciferin/luciferase assays of circumvallate tissue of knockout mice detected
      elevated levels of extracellular ATP. Electrophysiological recordings from two
      taste nerves, the chorda tympani and glossopharyngeal, revealed depressed
      responses to all taste stimuli in Entpd2-null mice. Responses were more depressed
      in the glossopharyngeal nerve than in the chorda tympani nerve and involved all
      taste qualities; responses in the chorda tympani were more depressed to sweet and
      umami stimuli than to other qualities. We suggest that the excessive levels of
      extracellular ATP in the Entpd2-knockout animals desensitize the P2X receptors
      associated with nerve fibers, thereby depressing taste responses. 

PMID- 23959884
TI  - Salicylic acid 3-hydroxylase regulates Arabidopsis leaf longevity by mediating
      salicylic acid catabolism.
AB  - The plant hormone salicylic acid (SA) plays critical roles in plant defense,
      stress responses, and senescence. Although SA biosynthesis is well understood,
      the pathways by which SA is catabolized remain elusive. Here we report the
      identification and characterization of an SA 3-hydroxylase (S3H) involved in SA
      catabolism during leaf senescence. S3H is associated with senescence and is
      inducible by SA and is thus a key part of a negative feedback regulation system
      of SA levels during senescence. The enzyme converts SA (with a Km of 58.29 uM) to
      both 2,3-dihydroxybenzoic acid (2,3-DHBA) and 2,5-DHBA in vitro but only 2,3-DHBA
      in vivo. The s3h knockout mutants fail to produce 2,3-DHBA sugar conjugates,
      accumulate very high levels of SA and its sugar conjugates, and exhibit a
      precocious senescence phenotype. Conversely, the gain-of-function lines contain
      high levels of 2,3-DHBA sugar conjugates and extremely low levels of SA and its
      sugar conjugates and display a significantly extended leaf longevity. This
      research reveals an elegant SA catabolic mechanism by which plants regulate SA
      levels by converting it to 2,3-DHBA to prevent SA overaccumulation. The research
      also provides strong molecular genetic evidence for an important role of SA in
      regulating the onset and rate of leaf senescence. 

PMID- 23959883
TI  - Two distinct forms of functional lateralization in the human brain.
AB  - The hemispheric lateralization of certain faculties in the human brain has long
      been held to be beneficial for functioning. However, quantitative relationships
      between the degree of lateralization in particular brain regions and the level of
      functioning have yet to be established. Here we demonstrate that two distinct
      forms of functional lateralization are present in the left vs. the right cerebral
      hemisphere, with the left hemisphere showing a preference to interact more
      exclusively with itself, particularly for cortical regions involved in language
      and fine motor coordination. In contrast, right-hemisphere cortical regions
      involved in visuospatial and attentional processing interact in a more
      integrative fashion with both hemispheres. The degree of lateralization present
      in these distinct systems selectively predicted behavioral measures of verbal and
      visuospatial ability, providing direct evidence that lateralization is associated
      with enhanced cognitive ability. 

PMID- 23959885
TI  - Torso-like functions independently of Torso to regulate Drosophila growth and
      developmental timing.
AB  - Activation of the Drosophila receptor tyrosine kinase Torso (Tor) only at the
      termini of the embryo is achieved by the localized expression of the maternal
      gene Torso-like (Tsl). Tor has a second function in the prothoracic gland as the
      receptor for prothoracicotropic hormone (PTTH) that initiates metamorphosis.
      Consistent with the function of Tor in this tissue, Tsl also localizes to the
      prothoracic gland and influences developmental timing. Despite these
      commonalities, in our studies of Tsl we unexpectedly found that tsl and tor have
      opposing effects on body size; tsl null mutants are smaller than normal, rather
      than larger as would be expected if the PTTH/Tor pathway was disrupted. We
      further found that whereas both genes regulate developmental timing, tsl does so
      independently of tor. Although tsl null mutants exhibit a similar length delay in
      time to pupariation to tor mutants, in tsl:tor double mutants this delay is
      strikingly enhanced. Thus, loss of tsl is additive rather than epistatic to loss
      of tor. We also find that phenotypes generated by ectopic PTTH expression are
      independent of tsl. Finally, we show that a modified form of tsl that can rescue
      developmental timing cannot rescue terminal patterning, indicating that Tsl can
      function via distinct mechanisms in different contexts. We conclude that Tsl is
      not just a specialized cue for Torso signaling but also acts independently of
      PTTH/Tor in the control of body size and the timing of developmental progression.
      These data highlight surprisingly diverse developmental functions for this sole
      Drosophila member of the perforin-like superfamily. 

PMID- 23959886
TI  - A nanoparticle formulation that selectively transfects metastatic tumors in mice.
AB  - Nanoparticle gene therapy holds great promise for the treatment of malignant
      disease in light of the large number of potent, tumor-specific therapeutic
      payloads potentially available for delivery. To be effective, gene therapy
      vehicles must be able to deliver their therapeutic payloads to metastatic lesions
      after systemic administration. Here we describe nanoparticles comprised of a core
      of high molecular weight linear polyethylenimine (LPEI) complexed with DNA and
      surrounded by a shell of polyethyleneglycol-modified (PEGylated) low molecular
      weight LPEI. Compared with a state-of-the-art commercially available in vivo gene
      delivery formulation, i.v. delivery of the core/PEGylated shell (CPS)
      nanoparticles provided more than a 16,000-fold increase in the ratio of tumor to
      nontumor transfection. The vast majority of examined liver and lung metastases
      derived from a colorectal cancer cell line showed transgene expression after i.v.
      CPS injection in an animal model of metastasis. Histological examination of
      tissues from transfected mice revealed that the CPS nanoparticles selectively
      transfected neoplastic cells rather than stromal cells within primary and
      metastatic tumors. However, only a small fraction of neoplastic cells (<1%)
      expressed the transgene, and the extent of delivery varied with the tumor cell
      line, tumor site, and host mouse strain used. Our results demonstrate that these
      CPS nanoparticles offer substantial advantages over previously described
      formulations for in vivo nanoparticle gene therapeutics. At the same time, they
      illustrate that major increases in the effectiveness of such approaches are
      needed for utility in patients with metastatic cancer. 

PMID- 23959887
TI  - Consequences of domain insertion on sequence-structure divergence in a superfold.
AB  - Although the universe of protein structures is vast, these innumerable structures
      can be categorized into a finite number of folds. New functions commonly evolve
      by elaboration of existing scaffolds, for example, via domain insertions. Thus,
      understanding structural diversity of a protein fold evolving via domain
      insertions is a fundamental challenge. The haloalkanoic dehalogenase superfamily
      serves as an excellent model system wherein a variable cap domain accessorizes
      the ubiquitous Rossmann-fold core domain. Here, we determine the impact of the
      cap-domain insertion on the sequence and structure divergence of the core domain.
      Through quantitative analysis on a unique dataset of 154 core-domain-only and cap
      domain-only structures, basic principles of their evolution have been uncovered.
      The relationship between sequence and structure divergence of the core domain is
      shown to be monotonic and independent of the corresponding type of domain insert,
      reflecting the robustness of the Rossmann fold to mutation. However, core domains
      with the same cap type share greater similarity at the sequence and structure
      levels, suggesting interplay between the cap and core domains. Notably, results
      reveal that the variance in structure maps to alpha-helices flanking the central
      beta-sheet and not to the domain-domain interface. Collectively, these results
      hint at intramolecular coevolution where the fold diverges differentially in the
      context of an accessory domain, a feature that might also apply to other
      multidomain superfamilies. 

PMID- 23959888
TI  - Subtype-specific control of P2X receptor channel signaling by ATP and Mg2+.
AB  - The identity and forms of activating ligands for ion channels are fundamental to
      their physiological roles in rapid electrical signaling. P2X receptor channels
      are ATP-activated cation channels that serve important roles in sensory signaling
      and inflammation, yet the active forms of the nucleotide are unknown. In
      physiological solutions, ATP is ionized and primarily found in complex with
      Mg(2+). Here we investigated the active forms of ATP and found that the action of
      MgATP(2-) and ATP(4-) differs between subtypes of P2X receptors. The slowly
      desensitizing P2X2 receptor can be activated by free ATP, but MgATP(2-) promotes
      opening with very low efficacy. In contrast, both free ATP and MgATP(2-) robustly
      open the rapidly desensitizing P2X3 subtype. A further distinction between these
      two subtypes is the ability of Mg(2+) to regulate P2X3 through a distinct
      allosteric mechanism. Importantly, heteromeric P2X2/3 channels present in sensory
      neurons exhibit a hybrid phenotype, characterized by robust activation by MgATP(2
      ) and weak regulation by Mg(2+). These results reveal the existence of two
      classes of homomeric P2X receptors with differential sensitivity to MgATP(2-) and
      regulation by Mg(2+), and demonstrate that both restraining mechanisms can be
      disengaged in heteromeric channels to form fast and sensitive ATP signaling
      pathways in sensory neurons. 

PMID- 23959889
TI  - Disruption of centrifugal inhibition to olfactory bulb granule cells impairs
      olfactory discrimination.
AB  - Granule cells (GCs) are the most abundant inhibitory neuronal type in the
      olfactory bulb and play a critical role in olfactory processing. GCs regulate the
      activity of principal neurons, the mitral cells, through dendrodendritic
      synapses, shaping the olfactory bulb output to other brain regions. GC
      excitability is regulated precisely by intrinsic and extrinsic inputs, and this
      regulation is fundamental for odor discrimination. Here, we used channelrhodopsin
      to stimulate GABAergic axons from the basal forebrain selectively and show that
      this stimulation generates reliable inhibitory responses in GCs. Furthermore,
      selective in vivo inhibition of GABAergic neurons in the basal forebrain by
      targeted expression of designer receptors exclusively activated by designer drugs
      produced a reversible impairment in the discrimination of structurally similar
      odors, indicating an important role of these inhibitory afferents in olfactory
      processing. 

PMID- 23959890
TI  - Pathogenetic mechanisms of amyloid A amyloidosis.
AB  - Systemic amyloid A (AA) amyloidosis is a serious complication of chronic
      inflammation. Serum AA protein (SAA), an acute phase plasma protein, is deposited
      extracellularly as insoluble amyloid fibrils that damage tissue structure and
      function. Clinical AA amyloidosis is typically preceded by many years of active
      inflammation before presenting, most commonly with renal involvement. Using dose
      dependent, doxycycline-inducible transgenic expression of SAA in mice, we show
      that AA amyloid deposition can occur independently of inflammation and that the
      time before amyloid deposition is determined by the circulating SAA
      concentration. High level SAA expression induced amyloidosis in all mice after a
      short, slightly variable delay. SAA was rapidly incorporated into amyloid,
      acutely reducing circulating SAA concentrations by up to 90%. Prolonged modest
      SAA overexpression occasionally produced amyloidosis after long delays and primed
      most mice for explosive amyloidosis when SAA production subsequently increased.
      Endogenous priming and bulk amyloid deposition are thus separable events, each
      sensitive to plasma SAA concentration. Amyloid deposits slowly regressed with
      restoration of normal SAA production after doxycycline withdrawal. Reinduction of
      SAA overproduction revealed that, following amyloid regression, all mice were
      primed, especially for rapid glomerular amyloid deposition leading to renal
      failure, closely resembling the rapid onset of renal failure in clinical AA
      amyloidosis following acute exacerbation of inflammation. Clinical AA amyloidosis
      rarely involves the heart, but amyloidotic SAA transgenic mice consistently had
      minor cardiac amyloid deposits, enabling us to extend to the heart the
      demonstrable efficacy of our unique antibody therapy for elimination of visceral
      amyloid. 

PMID- 23959891
TI  - Chronic alcohol produces neuroadaptations to prime dorsal striatal learning.
AB  - Drug addictions including alcoholism are characterized by degradation of
      executive control over behavior and increased compulsive drug seeking. These
      profound behavioral changes are hypothesized to involve a shift in the regulation
      of behavior from prefrontal cortex to dorsal striatum (DLS). Studies in rodents
      have shown that ethanol disrupts cognitive processes mediated by the prefrontal
      cortex, but the potential effects of chronic ethanol on DLS-mediated cognition
      and learning are much less well understood. Here, we first examined the effects
      of chronic EtOH on DLS neuronal morphology, synaptic plasticity, and
      endocannabinoid-CB1R signaling. We next tested for ethanol-induced changes in
      striatal-related learning and DLS in vivo single-unit activity during learning.
      Mice exposed to chronic intermittent ethanol (CIE) vapor exhibited expansion of
      dendritic material in DLS neurons. Following CIE, DLS endocannabinoid CB1
      receptor signaling was down-regulated, and CB1 receptor-dependent long-term
      depression at DLS synapses was absent. CIE mice showed facilitation of DLS
      dependent pairwise visual discrimination and reversal learning, relative to air
      exposed controls. CIE mice were also quicker to extinguish a stimulus-reward
      instrumental response and faster to reduce Pavlovian approach behavior under an
      omission schedule. In vivo single-unit recording during learning revealed that
      CIE mice had augmented DLS neuronal activity during correct responses.
      Collectively, these findings support a model in which chronic ethanol causes
      neuroadaptations in the DLS that prime for greater DLS control over learning. The
      shift to striatal dominance over behavior may be a critical step in the
      progression of alcoholism. 

PMID- 23959892
TI  - Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal
      Hreidarsson syndrome.
AB  - Telomeres repress the DNA damage response at the natural chromosome ends to
      prevent cell-cycle arrest and maintain genome stability. Telomeres are elongated
      by telomerase in a tightly regulated manner to ensure a sufficient number of cell
      divisions throughout life, yet prevent unlimited cell division and cancer
      development. Hoyeraal-Hreidarsson syndrome (HHS) is characterized by accelerated
      telomere shortening and a broad range of pathologies, including bone marrow
      failure, immunodeficiency, and developmental defects. HHS-causing mutations have
      previously been found in telomerase and the shelterin component telomeric repeat
      binding factor 1 (TRF1)-interacting nuclear factor 2 (TIN2). We identified by
      whole-genome exome sequencing compound heterozygous mutations in four siblings
      affected with HHS, in the gene encoding the regulator of telomere elongation
      helicase 1 (RTEL1). Rtel1 was identified in mouse by its genetic association with
      telomere length. However, its mechanism of action and whether it regulates
      telomere length in human remained unknown. Lymphoblastoid cell lines obtained
      from a patient and from the healthy parents carrying heterozygous RTEL1 mutations
      displayed telomere shortening, fragility and fusion, and growth defects in
      culture. Ectopic expression of WT RTEL1 suppressed the telomere shortening and
      growth defect, confirming the causal role of the RTEL1 mutations in HHS and
      demonstrating the essential function of human RTEL1 in telomere protection and
      elongation. Finally, we show that human RTEL1 interacts with the shelterin
      protein TRF1, providing a potential recruitment mechanism of RTEL1 to telomeres. 

PMID- 23959893
TI  - Glycosylated linkers in multimodular lignocellulose-degrading enzymes dynamically
      bind to cellulose.
AB  - Plant cell-wall polysaccharides represent a vast source of food in nature. To
      depolymerize polysaccharides to soluble sugars, many organisms use
      multifunctional enzyme mixtures consisting of glycoside hydrolases, lytic
      polysaccharide mono-oxygenases, polysaccharide lyases, and carbohydrate
      esterases, as well as accessory, redox-active enzymes for lignin
      depolymerization. Many of these enzymes that degrade lignocellulose are
      multimodular with carbohydrate-binding modules (CBMs) and catalytic domains
      connected by flexible, glycosylated linkers. These linkers have long been thought
      to simply serve as a tether between structured domains or to act in an inchworm
      like fashion during catalytic action. To examine linker function, we performed
      molecular dynamics (MD) simulations of the Trichoderma reesei Family 6 and Family
      7 cellobiohydrolases (TrCel6A and TrCel7A, respectively) bound to cellulose.
      During these simulations, the glycosylated linkers bind directly to cellulose,
      suggesting a previously unknown role in enzyme action. The prediction from the MD
      simulations was examined experimentally by measuring the binding affinity of the
      Cel7A CBM and the natively glycosylated Cel7A CBM-linker. On crystalline
      cellulose, the glycosylated linker enhances the binding affinity over the CBM
      alone by an order of magnitude. The MD simulations before and after binding of
      the linker also suggest that the bound linker may affect enzyme action due to
      significant damping in the enzyme fluctuations. Together, these results suggest
      that glycosylated linkers in carbohydrate-active enzymes, which are intrinsically
      disordered proteins in solution, aid in dynamic binding during the enzymatic
      deconstruction of plant cell walls. 

PMID- 23959894
TI  - Nonhuman primate model of schizophrenia using a noninvasive EEG method.
AB  - There is growing evidence that impaired sensory-processing significantly
      contributes to the cognitive deficits found in schizophrenia. For example, the
      mismatch negativity (MMN) and P3a event-related potentials (ERPs),
      neurophysiological indices of sensory and cognitive function, are reduced in
      schizophrenia patients and may be used as biomarkers of the disease. In agreement
      with glutamatergic theories of schizophrenia, NMDA antagonists, such as ketamine,
      elicit many symptoms of schizophrenia when administered to normal subjects,
      including reductions in the MMN and the P3a. We sought to develop a nonhuman
      primate (NHP) model of schizophrenia based on NMDA-receptor blockade using
      subanesthetic administration of ketamine. This provided neurophysiological
      measures of sensory and cognitive function that were directly comparable to those
      recorded from humans. We first developed methods that allowed recording of ERPs
      from humans and rhesus macaques and found homologous MMN and P3a ERPs during an
      auditory oddball paradigm. We then investigated the effect of ketamine on these
      ERPs in macaques. As found in humans with schizophrenia, as well as in normal
      subjects given ketamine, we observed a significant decrease in amplitude of both
      ERPs. Our findings suggest the potential of a pharmacologically induced model of
      schizophrenia in NHPs that can pave the way for EEG-guided investigations into
      cellular mechanisms and therapies. Furthermore, given the established link
      between these ERPs, the glutamatergic system, and deficits in other
      neuropsychiatric disorders, our model can be used to investigate a wide range of
      pathologies. 

PMID- 23959895
TI  - Neural mechanisms of communicative innovation.
AB  - Human referential communication is often thought as coding-decoding a set of
      symbols, neglecting that establishing shared meanings requires a computational
      mechanism powerful enough to mutually negotiate them. Sharing the meaning of a
      novel symbol might rely on similar conceptual inferences across communicators or
      on statistical similarities in their sensorimotor behaviors. Using
      magnetoencephalography, we assess spectral, temporal, and spatial characteristics
      of neural activity evoked when people generate and understand novel shared
      symbols during live communicative interactions. Solving those communicative
      problems induced comparable changes in the spectral profile of neural activity of
      both communicators and addressees. This shared neuronal up-regulation was
      spatially localized to the right temporal lobe and the ventromedial prefrontal
      cortex and emerged already before the occurrence of a specific communicative
      problem. Communicative innovation relies on neuronal computations that are shared
      across generating and understanding novel shared symbols, operating over temporal
      scales independent from transient sensorimotor behavior. 

PMID- 23959896
TI  - Synchronous interhemispheric Holocene climate trends in the tropical Andes.
AB  - Holocene variations of tropical moisture balance have been ascribed to orbitally
      forced changes in solar insolation. If this model is correct, millennial-scale
      climate evolution should be antiphased between the northern and southern
      hemispheres, producing humid intervals in one hemisphere matched to aridity in
      the other. Here we show that Holocene climate trends were largely synchronous and
      in the same direction in the northern and southern hemisphere outer-tropical
      Andes, providing little support for the dominant role of insolation forcing in
      these regions. Today, sea-surface temperatures in the equatorial Pacific Ocean
      modulate rainfall variability in the outer tropical Andes of both hemispheres,
      and we suggest that this mechanism was pervasive throughout the Holocene. Our
      findings imply that oceanic forcing plays a larger role in regional South
      American climate than previously suspected, and that Pacific sea-surface
      temperatures have the capacity to induce abrupt and sustained shifts in Andean
      climate. 

PMID- 23959897
TI  - Single point mutations in ATP synthase compensate for mitochondrial genome loss
      in trypanosomes.
AB  - Viability of the tsetse fly-transmitted African trypanosome Trypanosoma brucei
      depends on maintenance and expression of its kinetoplast (kDNA), the
      mitochondrial genome of this parasite and a putative target for veterinary and
      human antitrypanosomatid drugs. However, the closely related animal pathogens T.
      evansi and T. equiperdum are transmitted independently of tsetse flies and
      survive without a functional kinetoplast for reasons that have remained unclear.
      Here, we provide definitive evidence that single amino acid changes in the
      nuclearly encoded F1FO-ATPase subunit gamma can compensate for complete physical
      loss of kDNA in these parasites. Our results provide insight into the molecular
      mechanism of compensation for kDNA loss by showing FO-independent generation of
      the mitochondrial membrane potential with increased dependence on the ADP/ATP
      carrier. Our findings also suggest that, in the pathogenic bloodstream stage of
      T. brucei, the huge and energetically demanding apparatus required for kDNA
      maintenance and expression serves the production of a single F1FO-ATPase subunit.
      These results have important implications for drug discovery and our
      understanding of the evolution of these parasites. 

PMID- 23959898
TI  - Pulsed hydrogen-deuterium exchange mass spectrometry probes conformational
      changes in amyloid beta (Abeta) peptide aggregation.
AB  - Probing the conformational changes of amyloid beta (Abeta) peptide aggregation is
      challenging owing to the vast heterogeneity of the resulting soluble aggregates.
      To investigate the formation of these aggregates in solution, we designed an MS
      based biophysical approach and applied it to the formation of soluble aggregates
      of the Abeta42 peptide, the proposed causative agent in Alzheimer's disease. The
      approach incorporates pulsed hydrogen-deuterium exchange coupled with MS
      analysis. The combined approach provides evidence for a self-catalyzed
      aggregation with a lag phase, as observed previously by fluorescence methods.
      Unlike those approaches, pulsed hydrogen-deuterium exchange does not require
      modified Abeta42 (e.g., labeling with a fluorophore). Furthermore, the approach
      reveals that the center region of Abeta42 is first to aggregate, followed by the
      C and N termini. We also found that the lag phase in the aggregation of soluble
      species is affected by temperature and Cu(2+) ions. This MS approach has
      sufficient structural resolution to allow interrogation of Abeta aggregation in
      physiologically relevant environments. This platform should be generally useful
      for investigating the aggregation of other amyloid-forming proteins and
      neurotoxic soluble peptide aggregates. 

PMID- 23959899
TI  - Hypothalamo-pituitary and immune-dependent adrenal regulation during systemic
      inflammation.
AB  - Inflammation-related dysregulation of the hypothalamic-pituitary-adrenal (HPA)
      axis is central to the course of systemic inflammatory response syndrome or
      sepsis. The underlying mechanisms, however, are not well understood. Initial
      activation of adrenocortical hormone production during early sepsis depends on
      the stimulation of hypothalamus and pituitary mediated by cytokines; in late
      sepsis, there is a shift from neuroendocrine to local immune-adrenal regulation
      of glucocorticoid production. Therefore, the modulation of the local immune
      adrenal cross talk, and not of the neuroendocrine circuits involved in
      adrenocorticotropic hormone production, may be more promising in the prevention
      of the adrenal insufficiency associated with prolonged sepsis. In the present
      work, we investigated the function of the crucial Toll-like receptor (TLR)
      adaptor protein myeloid differentiation factor 88 (MyD88) in systemic and local
      activation of adrenal gland inflammation and glucocorticoid production mediated
      by lipopolysachharides (LPSs). To this end, we used mice with a conditional MyD88
      allele. These mice either were interbred with Mx1 Cre mice, resulting in systemic
      MyD88 deletion, predominantly in the liver and hematopoietic system, or were
      crossed with Akr1b7 Cre transgenic mice, resulting thereby in deletion of MyD88,
      which was adrenocortical-specific. Although reduced adrenal inflammation and HPA
      axis activation mediated by LPS were found in Mx1(Cre+)-MyD88(fl/fl) mice,
      adrenocortical-specific MyD88 deletion did not alter the adrenal inflammation or
      HPA-axis activity under systemic inflammatory response syndrome conditions. Thus,
      our data suggest an important role of immune cell rather than adrenocortical
      MyD88 for adrenal inflammation and HPA-axis activation mediated by LPS. 

PMID- 23959900
TI  - Beliefs about willpower determine the impact of glucose on self-control.
AB  - Past research found that the ingestion of glucose can enhance self-control. It
      has been widely assumed that basic physiological processes underlie this effect.
      We hypothesized that the effect of glucose also depends on people's theories
      about willpower. Three experiments, both measuring (experiment 1) and
      manipulating (experiments 2 and 3) theories about willpower, showed that,
      following a demanding task, only people who view willpower as limited and easily
      depleted (a limited resource theory) exhibited improved self-control after sugar
      consumption. In contrast, people who view willpower as plentiful (a nonlimited
      resource theory) showed no benefits from glucose--they exhibited high levels of
      self-control performance with or without sugar boosts. Additionally, creating
      beliefs about glucose ingestion (experiment 3) did not have the same effect as
      ingesting glucose for those with a limited resource theory. We suggest that the
      belief that willpower is limited sensitizes people to cues about their available
      resources including physiological cues, making them dependent on glucose boosts
      for high self-control performance.

PMID- 23959901
TI  - A physical explanation of the temperature dependence of physiological processes
      mediated by cilia and flagella.
AB  - The majority of biological rates are known to exhibit temperature dependence.
      Here I reveal a direct link between temperature and ecologically relevant rates
      such as swimming speeds in Archaea, Bacteria, and Eukaryotes as well as fluid
      pumping and filtration rates in many metazoans, and show that this relationship
      is driven by movement rates of cilia and flagella. I develop models of the
      temperature dependence of cilial and flagellar movement rates and evaluate these
      with an extensive compilation of data from the literature. The model captures the
      temperature dependence of viscosity and provides a mechanistic and biologically
      interpretable explanation for the temperature dependence of a range of
      ecologically relevant processes; it also reveals a clear dependence on both
      reaction rate-like processes and the physics of the environment. The
      incorporation of viscosity allows further insight into the effects of
      environmental temperature variation and of processes, such as disease, that
      affect the viscosity of blood or other body fluids. 

PMID- 23959902
TI  - Sight over sound in the judgment of music performance.
AB  - Social judgments are made on the basis of both visual and auditory information,
      with consequential implications for our decisions. To examine the impact of
      visual information on expert judgment and its predictive validity for performance
      outcomes, this set of seven experiments in the domain of music offers a
      conservative test of the relative influence of vision versus audition. People
      consistently report that sound is the most important source of information in
      evaluating performance in music. However, the findings demonstrate that people
      actually depend primarily on visual information when making judgments about music
      performance. People reliably select the actual winners of live music competitions
      based on silent video recordings, but neither musical novices nor professional
      musicians were able to identify the winners based on sound recordings or
      recordings with both video and sound. The results highlight our natural,
      automatic, and nonconscious dependence on visual cues. The dominance of visual
      information emerges to the degree that it is overweighted relative to auditory
      information, even when sound is consciously valued as the core domain content. 

PMID- 23959903
TI  - Segmenting the human genome based on states of neutral genetic divergence.
AB  - Many studies have demonstrated that divergence levels generated by different
      mutation types vary and covary across the human genome. To improve our still
      incomplete understanding of the mechanistic basis of this phenomenon, we analyze
      several mutation types simultaneously, anchoring their variation to specific
      regions of the genome. Using hidden Markov models on insertion, deletion,
      nucleotide substitution, and microsatellite divergence estimates inferred from
      human-orangutan alignments of neutrally evolving genomic sequences, we segment
      the human genome into regions corresponding to different divergence states--each
      uniquely characterized by specific combinations of divergence levels. We then
      parsed the mutagenic contributions of various biochemical processes associating
      divergence states with a broad range of genomic landscape features. We find that
      high divergence states inhabit guanine- and cytosine (GC)-rich, highly
      recombining subtelomeric regions; low divergence states cover inner parts of
      autosomes; chromosome X forms its own state with lowest divergence; and a state
      of elevated microsatellite mutability is interspersed across the genome. These
      general trends are mirrored in human diversity data from the 1000 Genomes
      Project, and departures from them highlight the evolutionary history of primate
      chromosomes. We also find that genes and noncoding functional marks [annotations
      from the Encyclopedia of DNA Elements (ENCODE)] are concentrated in high
      divergence states. Our results provide a powerful tool for biomedical data
      analysis: segmentations can be used to screen personal genome variants--including
      those associated with cancer and other diseases--and to improve computational
      predictions of noncoding functional elements.

PMID- 23959904
TI  - Transgenic mouse model for the study of enterovirus 71 neuropathogenesis.
AB  - Enterovirus 71 (EV71) typically causes mild hand-foot-and-mouth disease in
      children, but it can also cause severe neurological disease. Recently, epidemic
      outbreaks of EV71 with significant mortality have been reported in the Asia
      Pacific region, and EV71 infection has become a serious public health concern
      worldwide. However, there is little information available concerning EV71
      neuropathogenesis, and no vaccines or anti-EV71 drugs have been developed.
      Previous studies of this disease have used monkeys and neonatal mice that are
      susceptible to some EV71 strains as models. The monkey model is problematic for
      ethical and economical reasons, and mice that are more than a few weeks old lose
      their susceptibility to EV71. Thus, the development of an appropriate small
      animal model would greatly contribute to the study of this disease. Mice lack
      EV71 susceptibility due to the absence of a receptor for this virus. Previously,
      we identified the human scavenger receptor class B, member 2 (hSCARB2) as a
      cellular receptor for EV71. In the current study, we generated a transgenic (Tg)
      mouse expressing hSCARB2 with an expression profile similar to that in humans. Tg
      mice infected with EV71 exhibited ataxia, paralysis, and death. The most severely
      affected cells were neurons in the spinal cord, brainstem, cerebellum,
      hypothalamus, thalamus, and cerebrum. The pathological features in these Tg mice
      were generally similar to those of EV71 encephalomyelitis in humans and
      experimentally infected monkeys. These results suggest that this Tg mouse could
      represent a useful animal model for the study of EV71 infection. 

PMID- 23959905
TI  - Comet assay measures of DNA damage are predictive of bladder cancer cell
      treatment sensitivity in vitro and outcome in vivo.
AB  - Bladder cancer patients suffer significant treatment failure, including high
      rates of recurrence and poor outcomes for advanced disease. If mechanisms to
      improve tumour cell treatment sensitivity could be identified and/or if tumour
      response could be predicted, it should be possible to improve local-control and
      survival. Previously, we have shown that radiation-induced DNA damage, measured
      by alkaline Comet assay (ACA), correlates bladder cancer cell radiosensitivity in
      vitro. In this study we first show that modified-ACA measures of cisplatin and
      mitomycin-C-induced damage also correlate bladder cancer cell chemosensitivity in
      vitro, with essentially the same rank order for chemosensitivity as for
      radiosensitivity. Furthermore, ACA studies of radiation-induced damage in
      different cell-DNA substrates (nuclei, nucleoids and intact parent cells) suggest
      that it is a feature retained in the prepared nucleoids that is responsible for
      the relative damage sensitivity of bladder cancer cells, suggestive of
      differences in the organisation of DNA within resistant vs. sensitive cells.
      Second, we show that ACA analysis of biopsies from bladder tumours reveal that
      reduced DNA damage sensitivity associates with poorer treatment outcomes, notably
      that tumours with a reduced damage response show a significant association with
      local recurrence of non-invasive disease and that reduced damage response was a
      better predictor of recurrence than the presence of high-risk histology in this
      cohort. In conclusion, this study demonstrates that mechanisms governing
      treatment-induced DNA damage are both central to and predictive of bladder cancer
      cell treatment sensitivity and exemplifies a link between DNA damage resistance
      and both treatment response and tumour aggression. 

PMID- 23959906
TI  - What role do plain radiographs have in assessing the skeletally immature
      acromioclavicular joint?
AB  - BACKGROUND: Because of incomplete ossification of the coracoid process and
      acromion, acromioclavicular joint configuration in the skeletally immature
      patient differs from that of adults. Although comparison to radiographic
      standards for this joint is critical in the evaluation of acromioclavicular joint
      injuries, these standards are not well defined for children or adolescents.
      QUESTIONS/PURPOSES: We therefore sought to determine (1) the reliability of
      numerous radiographic measurements of the skeletally immature acromioclavicular
      joint, including the vertical and shortest coracoclavicular interval, and the
      acromioclavicular joint offset; (2) the timing of ossification of the acromion
      and coracoid in males and females; and (3) the differences in the values of these
      radiographic measurements based on age and sex. METHODS: This study was based on
      a total of 485 subjects, 8 to 18 years old, who underwent conventional AP view
      radiographs of both shoulders. The 485 subjects were included to assess normal
      configuration around the acromioclavicular joint and 466 of these subjects were
      evaluated for comparison between both sides. The vertical and shortest
      coracoclavicular interval, coracoclavicular clavicle width ratio,
      acromioclavicular joint offset, and difference of the coracoclavicular interval
      of both sides were measured. A reliability test was conducted before obtaining
      the main measurements. The relationship of measurements with sex, age, and stage
      of ossification was evaluated. RESULTS: The vertical and shortest
      coracoclavicular interval showed excellent reliability (intraclass correlation
      coefficient ([ICC], 0.918 and 0.934). The acromioclavicular joint offset showed
      low reliability (ICC, 0.543). The ossification centers of the acromion and the
      coracoid processes appeared and fused earlier in females than in males. The
      vertical coracoclavicular interval, which was not affected by partial
      ossification of the coracoid process, was less than 11 mm in the 90% quantile of
      total subjects in males and 10 mm in the 90% quantile in females. The difference
      of the vertical coracoclavicular interval of both sides was less than 50% in 436
      of 466 (93.4%) patients. CONCLUSIONS: The vertical coracoclavicular interval was
      the best parameter to assess acromioclavicular joint dislocation in skeletally
      immature patients. Comparison of both sides of the acromioclavicular joint could
      help to inform physicians in predicting the need for additional evaluations.

PMID- 23959907
TI  - Death, taxes, and trapeziometacarpal arthrosis.
AB  - BACKGROUND: Hand surgeons treat trapeziometacarpal arthrosis as if everyone with
      the disease presents for treatment despite evidence that suggests that
      trapeziometacarpal arthrosis is a normal part of human aging for which--it seems
      safe to assume--most people never seek medical attention. QUESTIONS/PURPOSES: The
      aims of our study were (1) to confirm the prevalence of radiographic
      trapeziometacarpal arthrosis in a very large sample and to determine if age and
      sex are associated with (2) any radiographic evidence of trapeziometacarpal
      arthrosis; and (3) radiographic evidence of severe trapeziometacarpal arthrosis.
      METHODS: A total of 2321 patients 31 years or older with radiographs obtained
      during treatment of a distal radius fracture at a tertiary care medical center
      emergency department between 2002 and 2012 were analyzed. Trapeziometacarpal
      arthrosis was graded using the 3-point scale of Sodha et al. (none, definite,
      destroyed trapeziometacarpal joint); we used regression analyses to determine the
      association of age (in 10-year age groups) and sex with the presence of
      trapeziometacarpal arthrosis. RESULTS: The prevalence of trapeziometacarpal
      arthrosis steadily increased to 85% between the ages of 71 and 80 years and
      reached 100% in women (with 50% of them being classified as severe) aged 91 years
      or older and 93% in men of 81 years or older. Severe arthrosis was more prevalent
      at earlier ages among women and reached 35% in women and 34% in men who were 81
      years or older. Logistic regression identified higher age as the strongest factor
      associated with trapeziometacarpal arthrosis, but sex was also a factor.
      CONCLUSIONS: Radiographic trapeziometacarpal arthrosis is an expected part of
      human aging. Given that only three patients in this large cohort had evidence of
      prior surgery, it seems that most people adapt to trapeziometacarpal arthrosis.
      Treatments that optimize adaptation in patients who present with
      trapeziometacarpal arthrosis-related symptoms and disability merit additional
      study.

PMID- 23959908
TI  - Correlations between blood glucose and breath components from portable gas
      sensors and PTR-TOF-MS.
AB  - Acetone is one of the most abundant volatile compounds in the human breath and
      might be important for monitoring diabetic patients. Here, a portable acetone
      sensor consisting of flame-made, nanostructured, Si-doped WO3 sensing films was
      used to analyse the end tidal fraction of the breath (collected in Tedlar bags)
      from eight healthy volunteers after overnight fasting (morning) and after lunch
      (afternoon). After breath sampling, the gaseous components were also analysed by
      proton transfer reaction time-of-flight mass spectrometry (PTR-TOF-MS), and each
      person's blood glucose level was measured. The portable sensor accurately
      detected the presence of acetone with fast response/recovery times (<12 s) and a
      high signal-to-noise ratio. Statistical analysis of the relationship between the
      PTR-TOF-MS measurements of breath gases (e.g., acetone, isoprene, ethanol and
      methanol), sensor response and the blood glucose level was performed for both
      sampling periods. The best correlations were found after overnight fasting
      (morning): in particular, between blood glucose level and breath acetone
      (Pearson's 0.98 and Spearman's 0.93). Whereas the portable sensor response
      correlated best with the blood glucose (Pearson's 0.96 and Spearman's 0.81) and
      breath acetone (Pearson's 0.92 and Spearman's 0.69). 

PMID- 23959909
TI  - Level anti-crossings are a key factor for understanding para-hydrogen-induced
      hyperpolarization in SABRE experiments.
AB  - Various hyperpolarization methods are able to enhance the sensitivity of nuclear
      magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) by
      several orders of magnitude. Among these methods are para-hydrogen-induced
      polarization (PHIP) and signal amplification by reversible exchange (SABRE),
      which exploit the strong nuclear alignment of para-hydrogen. Several SABRE
      experiments have been reported but, so far, it has not been possible to account
      for the experimentally observed sign and magnetic-field dependence of substrate
      polarization. Herein, we present an analysis based on level anti-crossings
      (LACs), which provides a complete understanding of the SABRE effect. The field
      dependence of both net and anti-phase polarization is measured for several
      ligands, which can be reproduced by the theory. The similar SABRE field
      dependence for different ligands is also explained. In general, the LAC concept
      allows complex spin dynamics to be unraveled, and is crucial for optimizing the
      performance of novel hyperpolarization methods in NMR and MRI techniques. 

PMID- 23959910
TI  - Patient-specific modelling of head-up tilt.
AB  - Short-term cardiovascular responses to head-up tilt (HUT) involve complex
      cardiovascular regulation in order to maintain blood pressure at homoeostatic
      levels. This manuscript presents a patient-specific model that uses heart rate as
      an input to fit the dynamic changes in arterial blood pressure data during HUT.
      The model contains five compartments representing arteries and veins in the upper
      and lower body of the systemic circulation, as well as the left ventricle
      facilitating pumping of the heart. A physiologically based submodel describes
      gravitational pooling of the blood into the lower extremities during HUT, and a
      cardiovascular regulation model adjusts cardiac contractility and vascular
      resistance to the blood pressure changes. Nominal parameter values are computed
      from patient-specific data and literature estimates. The model is rendered
      patient specific via the use of parameter estimation techniques. This process
      involves sensitivity analysis, prediction of a subset of identifiable parameters,
      and non-linear optimization. The approach proposed here was applied to the
      analysis of aortic and carotid HUT data from five healthy young subjects. Results
      showed that it is possible to identify a subset of model parameters that can be
      estimated allowing the model to fit changes in arterial blood pressure observed
      at the level of the carotid bifurcation. Moreover, the model estimates
      physiologically reasonable values for arterial and venous blood pressures, blood
      volumes and cardiac output for which data are not available. 

PMID- 23959911
TI  - Safety and efficacy of autologous hemopoietic progenitor cell collection in
      tandem with hemodialysis in multiple myeloma with myeloma cast nephropathy.
AB  - Autologous hemopoietic progenitor cell (HPC) collection is the most frequent
      indication for an apheresis procedure in patients with multiple myeloma, up to
      10% of whom may also require hemodialysis because of myeloma kidney. We
      investigated whether HPC collection could be performed in tandem with
      hemodialysis, to avoid extra outpatient visits for extracorporeal procedures,
      without compromising the efficacy of the hemodialysis, the HPC collection
      efficiency (CE) or patient safety. Four dialysis-dependent patients with multiple
      myeloma underwent 5 large volume leukapheresis HPC collections in tandem with
      hemodialysis. Under our protocol, all of the blood processed through the
      apheresis instrument was dialyzed against a standard calcium-rich bath prior to
      being returned to the patient, therefore no supplemental calcium was needed. No
      significant changes in pulse rate (P = 0.625) or mean arterial pressure (P =
      0.188) were noted between the start and end of the procedures. The patients
      exhibited no signs or symptoms of hypocalcemia or other adverse effects.
      Calculated urea reduction ratios ranged between 62.5 and 73.9%, and HPC CE was
      between 53 and 84% for 4 of the 5 procedures, indicating that there was no
      compromise of either procedure when performed in tandem. Ionized calcium measured
      at the beginning, midpoint and end of every procedure did not change (P = 0.954).
      The two patients who proceeded to autologous HPC transplant engrafted on Days 11
      and 10, respectively. We conclude that autologous HPC collection can safely be
      performed in tandem with hemodialysis without compromising the efficacy of
      dialysis, HPC CE, or patient safety.

PMID- 23959912
TI  - Abraham Colles and his contributions to anatomy.
AB  - Abraham Colles is known among the medical community for his detailed description
      of Colles' fracture, one of the most common occurring skeletal injuries. It is
      remarkable that something as seemingly simple as the diagnosis of Colles'
      fracture had not been established until nearly 200 years ago. While that may have
      been his most well known accomplishment, Colles made several other contributions
      to medicine across multiple fields of practice. In the field of anatomy, he is
      also credited for his discovery and description of Colles' fascia and Colles'
      ligament. Less commonly known, however, are his clinical observations and offered
      treatment regimens for syphilis, as well as his achievement in performing the
      first surgery for axillary artery aneurysm. The current paper will review the
      life and contributions of this early surgeon and anatomist.

PMID- 23959914
TI  - Different risk-increasing drugs in recurrent versus single fallers: are recurrent
      fallers a distinct population?
AB  - BACKGROUND: Polypharmacy, and specifically the use of multiple fall-risk
      increasing drugs (FRID), have been associated with increased risk of falling in
      older age. However, it is not yet clear whether the known set of FRIDs can be
      extrapolated to recurrent fallers, since they form a distinct group of more
      vulnerable older persons with different characteristics. OBJECTIVES: We aim to
      investigate which classes of medications are associated with recurrent falls in
      elderly patients visiting the Emergency Department (ED) after a fall. METHODS:
      This study had a cross-sectional design and was conducted in the ED of an
      academic medical center. Patients who sustained a fall, 65 years or older, and
      who visited the ED between 2004 and 2010 were invited to fill in a validated fall
      questionnaire designed to assess patient and fall characteristics (CAREFALL
      Triage Instrument [CTI]). We translated self-reported medications to anatomical
      therapeutic chemical (ATC) codes (at the second level). Univariate logistic
      regression analysis was performed to explore the association between medication
      classes and the outcome parameter (recurrent fall). Multivariate logistic
      regression was used to assess the associations after adjustment to potential
      confounders. RESULTS: In total 2,258 patients participated in our study, of whom
      39 % (873) had sustained two or more falls within the previous year. After
      adjustment for the potential confounders, drugs for acid-related disorders
      (adjusted odds ratio [aOR] 1.29; 95 % CI 1.03-1.60), analgesics (aOR 1.22; 95 %
      CI 1.06-1.41), anti-Parkinson drugs (aOR 1.59; 95 % CI 1.02-2.46), nasal
      preparations (aOR 1.49; 95 % CI 1.07-2.08), ophthalmologicals (aOR 1.51; 95 % CI
      1.10-2.09); antipsychotics (aOR 2.21; 95 % CI 1.08-4.52), and antidepressants
      (aOR 1.64; 95 % CI 1.13-2.37) remained statistically significantly associated
      with an ED visit due to a recurrent fall. CONCLUSIONS: Known FRIDs, such as
      psychotropic drugs, also increase the risk of recurrent falls. However, we found
      four relatively new classes that showed significant association with recurrent
      falls. In part, these classes may act as markers of frailty and comorbidity, or
      they may reflect differences in the risk factors affecting the older, frailer
      population that tends to sustain recurrent falls. Further investigation is needed
      to elucidate causes and ways to prevent recurrent falls.

PMID- 23959915
TI  - Energy substrate influences the effect of the timing of the first embryonic
      cleavage on the development of in vitro-produced porcine embryos in a sex-related
      manner.
AB  - In vitro culture conditions and certain events during the earliest stages of
      development are linked to embryonic survival, possibly in a sex-related manner.
      In vitro-produced (IVP) porcine embryos cultured with glucose (IVC-Glu) or
      pyruvate-lactate (IVC-PL) were tested for any relationship between the timing of
      the first embryonic cleavage and development and sex ratio. The embryos were
      assigned to IVC-Glu or IVC-PL groups and classified depending on the timing of
      their first cleavage: 24, 26, 30, and 48 hr post-insemination (hpi). They were
      cultured separately in vitro and evaluated for cleavage rate and pattern,
      blastocyst rate and stage, cell number, apoptosis, and sex ratio. Regardless of
      energy source, the percentage of two-cell stage and fragmented embryos at the
      time of their first cleavage was, respectively, higher and lower in early
      cleaving embryos. Those embryos cleaved by 24 hpi developed to blastocysts at a
      higher rate (IVC-Glu: 37.90 +/- 3.06%; IVC-PL: 38.73 +/- 4.08%) than those
      cleaved between 30 and 48 hpi (IVC-Glu: 5.87 +/- 3.02%; IVC-PL: 8.41 +/- 3.50%).
      Furthermore, a shift toward males was seen among embryos first cleaved before 30
      hpi, versus towards females among those cleaved later. The early-cleaving
      embryos, only from the IVC-PL group, had a higher proportion of expanded
      blastocysts (81.05 +/- 6.54% vs. 13.33 +/- 13.33%) with higher cell numbers than
      their late-cleaving counterparts. Moreover, a shift toward males only appeared at
      the blastocyst stage in IVC-PL embryos. These findings confirm that the timing of
      the first cleavage influences development of IVP porcine embryos in a sex-related
      manner, and it depends on the main energy source of the in vitro culture medium.

PMID- 23959913
TI  - Aging, antiretrovirals, and adherence: a meta analysis of adherence among older
      HIV-infected individuals.
AB  - INTRODUCTION: Older adults are generally considered to be at greater risk for
      medication non-adherence due to factors such as medication complexity, side
      effects, cost, and cognitive decline. However, this generalization may not apply
      to older adults with human immunodeficiency virus (HIV). Regardless of age,
      suboptimal adherence to antiretroviral therapy (ART) can lead to increased viral
      load, immunosuppression, drug-resistant viral strains, co-morbidities, and
      opportunistic infections. Understanding trends of adherence to ART among older
      adults is critical, especially as the population of people living with HIV grows
      older. OBJECTIVES: The purpose of this systematic review and meta-analysis is to
      determine if older individuals with HIV are less likely to be non-adherent to
      antiretroviral therapy than younger individuals with HIV. DESIGN: A systematic
      search in PubMed, Embase, and PsycINFO was conducted to identify peer-reviewed
      articles evaluating adherence to ART in older adults. Two independent reviewers
      screened abstracts, applied inclusion criteria, and appraised study quality. The
      bibliographies of qualifying studies were searched. Data were abstracted from
      studies by two independent authors. Meta-analyses were conducted, and adherence
      levels were reported as the relative risk of non-adherence in older individuals
      compared to younger individuals. RESULTS: The systematic search yielded 1,848
      abstracts. Twelve studies met full inclusion criteria. The overall meta-analysis
      found that older age reduced risk for nonadherence by 27 % (relative risk (RR)
      0.72, 95 % confidence interval (CI) 0.64-0.82). Studies assessing both short-term
      and long-term adherence demonstrated a significant reduction in non-adherence
      among older patients (RR 0.75, 95 % CI 0.64-0.87 and RR 0.65, 95 % CI 0.50-0.85,
      respectively). CONCLUSIONS: Older adults with HIV have a reduced risk for non
      adherence to ART than their younger counterparts. Future studies should seek to
      elucidate contributing factors of adherence among older individuals with HIV.

PMID- 23959916
TI  - Medication assessment tool to detect care issues from routine data: a pilot study
      in primary care.
AB  - BACKGROUND: Medication assessment tools (MATs) may be implemented in routine
      electronic data sources in order to identify patients with opportunities for
      optimisation of medication therapy management (MTM) and follow-up by a multi
      disciplinary team. OBJECTIVE: (1) To demonstrate the use of a MAT for
      cardiovascular conditions (MAT CVC) as a means of profiling potential
      opportunities for MTM optimisation in primary care and (2) to assess the
      performance of MAT CVC in identifying actual opportunities for better care.
      SETTING: Members of a pharmacotherapy discussion group, i.e. two single-handed
      general practitioners (GPs), three GP partners, and community pharmacists (CPs)
      from each of two community pharmacies, in a rural part of the Netherlands.
      METHODS: MAT CVC comprises 21 medication assessment criteria, each of which is
      designed to detect a specific care issue and to check whether it is 'addressed'
      by provision of guideline recommended care or 'open' in the presence ('open
      explained') or absence ('open unexplained') of pre-specified explanations for
      guideline deviations. (1) Relevant data was extracted from linked GP and CP
      electronic records and MAT CVC assessment was conducted to profile the population
      of CVC patients registered with both, participating CPs and GPs, in terms of
      'open unexplained' care issues. (2) A purposive sample of patients with 'open
      unexplained' care issues was reviewed by each patient's GP. MAIN OUTCOME
      MEASURES: Number and proportion of 'open unexplained' care issues per MAT CVC
      criterion and per patient. The number of patients with MAT CVC detected 'open
      unexplained' care issues to be reviewed (NNR) in order to identify one that
      requires changes in MTM. RESULTS: In 1,876 target group patients, MAT CVC
      identified 6,915 care issues, of which 2,770 (40.1 %) were 'open unexplained'. At
      population level, ten MAT CVC criteria had particularly high potential for
      quality improvement. At patient level, 1,277 (68.1 %) target group patients had
      at least one 'open unexplained' care issue. For patients with four or more 'open
      unexplained' care issues, the NNR was 2 (95 % CI 2-2). CONCLUSION: The study
      demonstrates potential ways of using MA TCVC as a key component of a
      collaborative MTM system. Strategies that promote documentation and sharing of
      explanations for deviating from guideline recommendations may enhance the utility
      of the approach.

PMID- 23959917
TI  - Virological diagnosis and management of two cases of congenital measles.
AB  - Measles is a highly contagious viral infection causing congenital infections with
      a risk of neurological complications in the newborn. Two cases of measles, which
      occurred in pregnant women within 14 days before the delivery, are described.
      Mother-to-child transmission of the virus was documented in the newborns either
      by RT-PCR in saliva or by IgM detection in blood. The measles strains evidenced
      in saliva samples were genotyped and belonged to the D4 Genotype. An early viral
      RT-PCR detection allowed successful immunoglobulin prophylaxis in one newborn
      taking into account that the duration between the onset of the skin rash in the
      mother and the delivery was less than 6 days. Twenty-four months later, none of
      the newborns developed classical or neurological clinical signs of measles
      infection. Measles RT-PCR assay in salivary samples can be used before symptoms
      develop in the infant to confirm early mother-to-child transmission, therefore
      permitting the use of an immunoglobulin prophylaxis in the newborn.

PMID- 23959918
TI  - Comparative study of the possible protective effects of cinnamic acid and
      cinnamaldehyde on cisplatin-induced nephrotoxicity in rats.
AB  - This study aimed to assess the protective effect of cinnamic acid (CA) and
      cinnamaldehyde (CD) against cisplatin-induced nephrotoxicity. A single dose of
      cisplatin (5 mg/kg), injected intraperitoneally to male rats, caused significant
      increases in serum urea, creatinine levels, and lipid peroxides measured as the
      malondialdehyde content of kidney, with significant decreases in serum albumin,
      reduced glutathione, and the activity of antioxidant enzymes (catalase,
      superoxide dismutase, and glutathione peroxidase) of kidney as compared with the
      control group. On the other hand, administration of CA (50 mg/kg, p.o.) or CD (40
      mg/kg, p.o.) for 7 days before cisplatin ameliorated the cisplatin-induced
      nephrotoxicity as indicated by the restoration of kidney function and oxidative
      stress parameters. Furthermore, they reduced the histopathological changes
      induced by cisplatin. In conclusion, CA and CD showed protective effects against
      cisplatin-induced nephrotoxicity where CD was more effective than CA; affects
      that might be attributed to their antioxidant activities. 

PMID- 23959919
TI  - Bonding pathways of high-pressure chemical transformations.
AB  - A three-stage bonding pathway towards high-pressure chemical transformations from
      molecular precursors or intermediate states has been identified by first
      principles simulations. With the evolution of principal stress tensor components
      in the response of chemical bonding to compressive loading, the three stages can
      be defined as the van der Waals bonding destruction, a bond breaking and forming
      reaction, and equilibrium of new bonds. The three-stage bonding pathway leads to
      the establishment of a fundamental principle of chemical bonding under
      compression. It reveals that during high-pressure chemical transformation,
      electrons moving away from functional groups follow anti-addition, collision-free
      paths to form new bonds in counteracting the local stress confinement. In
      applying this principle, a large number of molecular precursors were identified
      for high-pressure chemical transformations, resulting in new materials. 

PMID- 23959920
TI  - Total antioxidant intake in relation to prostate cancer incidence in the Health
      Professionals Follow-Up Study.
AB  - Epidemiologic evidence on the association of antioxidant intake and prostate
      cancer incidence is inconsistent. Total antioxidant intake and prostate cancer
      incidence have not previously been examined. Using the ferric-reducing
      antioxidant potential (FRAP) assay, the total antioxidant content (TAC) of diet
      and supplements was assessed in relation to prostate cancer incidence. A
      prospective cohort of 47,896 men aged 40-75 years was followed from 1986 to 2008
      for prostate cancer incidence (N = 5,656), and they completed food frequency
      questionnaires (FFQs) every 4 years. A FRAP value was assigned to each item in
      the FFQ, and for each individual, TAC scores for diet, supplements and both
      (total) were calculated. Major contributors of TAC intake at baseline were coffee
      (28%), fruit and vegetables (23%) and dietary supplements (23%). In multivariate
      analyses for dietary TAC a weak inverse association was observed [highest versus
      lowest quintiles: 0.91 (0.83-1.00, p-trend = 0.03) for total prostate cancer and
      0.81 (0.64-1.01, p-trend = 0.04) for advanced prostate cancer]; this association
      was mainly due to coffee. No association of total TAC on prostate cancer
      incidence was observed. A positive association with lethal and advanced prostate
      cancers was observed in the highest quintile of supplemental TAC intake: 1.28
      (0.98-1.65, p-trend < 0.01) and 1.15 (0.92-1.43, p-trend = 0.04). The weak
      association between dietary antioxidant intake and reduced prostate cancer
      incidence may be related to specific antioxidants in coffee, to nonantioxidant
      coffee compounds or other effects of drinking coffee. The indication of increased
      risk for lethal and advanced prostate cancers with high TAC intake from
      supplements warrants further investigation. 

PMID- 23959922
TI  - How filopodia pull: what we know about the mechanics and dynamics of filopodia.
AB  - In recent years, the dynamic, hair-like cell protrusions called filopodia have
      attracted considerable attention. They have been found in a multitude of
      different cell types and are often called "sensory organelles," since they seem
      to sense the mechanical and chemical environment of a cell. Once formed,
      filopodia can exhibit complex behavior, they can grow and retract, push or pull,
      and transform into distinct structures. They are often found to make first
      adhesive contact with the extracellular matrix, pathogens or with adjacent cells,
      and to subsequently exert pulling forces. Much is known about the cytoskeletal
      players involved in filopodia formation, but only recently have we started to
      explore the mechanics of filopodia together with the related cytoskeletal
      dynamics. This review summarizes current advancements in our understanding of the
      mechanics and dynamics of filopodia, with a focus on the molecular mechanisms
      behind filopodial force exertion.

PMID- 23959921
TI  - Effect of selenium on fluoride-induced changes in synaptic plasticity in rat
      hippocampus.
AB  - This study was conducted to further explore the effect of selenium on fluoride
      induced changes in the synaptic plasticity in rat hippocampus. Animals were
      randomly divided into control group, F group (sodium fluoride: 50 mg/L), three Se
      groups (sodium selenite: 0.375, 0.75, and 1.5 mg/L), and three F+Se groups
      (sodium fluoride: 50 mg/L; sodium selenite:0.375, 0.75, and 1.5 mg/L) and
      subjected to an exposure time of 6 months. The changes in synaptic plasticity in
      rat hippocampus were observed by electron microscopy. Compared with the fluoride
      group, the length of the synaptic active zone and the thickness of the
      postsynaptic density (PSD) increased significantly, whereas the width of the
      synaptic cleft decreased with high significance in the F+Se (0.75 mg/L) group.
      Moreover, the nitric oxide synthase activity and the nitric oxide content in the
      hippocampus decreased significantly in the F+Se (0.75 and 1.5 mg/L) groups.
      Furthermore, reverse transcriptase polymerase chain reaction and Western blot
      analyses showed that postsynaptic density-93 (PSD-93) expression in the
      hippocampus was increased significantly, whereas postsynaptic density-95 (PSD-95)
      expression decreased significantly in the fluoride group compared with the
      control group. The PSD-93 expression was inhibited in the three F+Se groups,
      whereas the opposite result was observed in PSD-95 expression. Based on the
      results, the optimal selenium dosage range that can antagonize the neurotoxicity
      of fluorosis is from 0.75 to 1.5 mg/L. The changes in PSD-93 expression may be
      the key factor to fluoride-induced central nervous toxicity and the effect of
      selenium intervention.

PMID- 23959923
TI  - Toluene and lithium amide diffusion into polystyrene: a slice-selective NMR
      spectroscopic study.

PMID- 23959925
TI  - The Autism-Spectrum Quotient in university students: pattern of changes in its
      scores and associated factors.
AB  - INTRODUCTION: Support to university students with autism spectrum disorders (ASD)
      is becoming increasingly important. To determine the validity of the Autism
      Spectrum Quotient (AQ) for ASD screening of university students, we conducted
      longitudinal measurements of the AQ in a large sample of university students and
      investigated the possibility of changes in the AQ and associated factors.
      METHODS: The AQ, University Personality Inventory (UPI), and the willingness of
      the students to be interviewed were determined at admission in students from four
      departments of Kochi University; the AQ was determined again in the second year.
      Changes in the AQ and associated factors were analyzed statistically. RESULTS:
      The number of valid responses in the initial survey was 3427 (87.2%). The AQ was
      significantly higher in the group with high UPI scores (F = 156.08, P < 0.001).
      Of the 486 students interviewed at admission, 22 had suspected ASD. The
      sensitivity/specificity of the AQ for ASD was 81.8%/92.0%. A total of 319 (11.0%)
      students responded to the second-year survey, which revealed significant decrease
      of the AQ in the group with high AQ values at admission. DISCUSSION: The AQ
      measured at admission was correlated with the UPI score, regardless of the sex or
      department; in the second survey, the scores decreased significantly in those
      with high AQ values at admission, suggesting that an unstable mental state can
      produce a temporary increase of the AQ scores.

PMID- 23959924
TI  - Do olympic athletes train as in the Paleolithic era?
AB  - Every 4 years, approximately 10,000 athletes participate in the Olympic Games.
      These athletes have dedicated several years of physical training to achieve the
      best possible performance on a given day. Their preparation has been supported by
      expert coaches and an army of sport scientists, whose overall responsibility is
      to ensure that the athletes are in peak condition for their event. Although every
      athlete prepares specifically for the unique physiological challenges of their
      event, all athletes have one common characteristic: they are Homo sapiens. They
      share a unique genome, which is the result of evolutionary forces beyond their
      individual control. Although studies on the influence of different genetic
      polymorphisms on selected athletic events have been proven to be of limited
      utility, a body of evidence--from molecular biology to whole-body measures-
      suggests that training adaptations are enhanced when the stimulus closely
      resembles the activity pattern of human ancestors. Because genetic evolutionary
      changes occur slowly in Homo sapiens, and the traditional physical activity and
      dietary patterns of Homo sapiens have undergone rapid and dramatic changes in
      previous centuries, we propose that modern humans are physiologically better
      adapted to training modes and nutritional strategies similar to the ones that
      their hominid ancestors evolved on, rather than those supported by modern
      societies. Such an ancestral pattern was mainly characterized by the prevalence
      of daily bouts of prolonged, low-intensity, aerobic-based activities interspersed
      with periodic, short-duration, high-intensity bursts of activity. On some
      occasions, such activity patterns were undertaken with low carbohydrate
      availability. Specific activities that enhanced strength and power were typically
      performed after aerobic activities. We present scientific evidence to support the
      appropriateness of this model, and we propose that future studies should address
      this hypothesis in a multitude of different sporting activities, by assessing the
      genetic responses to and performance-based outcomes of different training
      stimuli. Such information would provide data on which sport scientists and
      coaches could better prepare athletes and manage their training process.

PMID- 23959926
TI  - Identifying parentage using molecular markers: improving accuracy of studbook
      records for a captive flock of marabou storks (Leptoptilos crumeniferus).
AB  - Extra-pair copulations (EPCs) leading to extra-pair fertilization (EPF) are
      common in avian mating systems, despite the prevalence of observed social
      monogamy in many species. Colonially breeding birds are interesting species to
      investigate the prevalence of EPCs and EPF because they show nesting habits
      including close proximity of nest sites and sexual partners, which are proposed
      to promote alternative reproductive tactics. Endemic to Africa, the colonial
      marabou stork (Leptoptilos crumeniferus) is one of the most commonly held avian
      species in North American zoos. The aims of this study were to use genetic
      information to verify parentage in a population of marabou stork housed at
      Disney's Animal Kingdom(r) based on five microsatellite loci and to investigate
      reproductive behavior. We compared genetic analyses of parents and offspring to
      studbook data collected through behavioral observations of parental behavior at
      the nest. Using genetic analyses to reconstruct the pedigree of the marabou stork
      flock using the program COLONY led to improvement of studbook records by
      determining parentage of an individual that had previously unknown parentage, and
      identified one individual that had a sire that differed genetically from studbook
      records. An important contribution of our analyses was the identification and
      verification of the most likely parents for offspring hatched in this colony and
      improving incorrect or undocumented parentage in the studbook. Additionally, the
      colonial nature of this species makes it difficult to observe and understand
      reproductive behavior. Gaining better understanding of the mating system of a
      species is essential for successful breeding and captive management.

PMID- 23959927
TI  - Giulio Cesare Casseri (c. 1552-1616): the servant who became an anatomist.
AB  - Julius Casserius was born in a poor family in Piacenza in 1552. As a young man,
      he moved to Padua and soon after, he became a servant to Fabricius, a noted
      anatomist and professor at the Universita Artista, who quickly became his mentor.
      Casserius eventually attended the University of Padua and received a degree in
      medicine and philosophy. In the following years, a rivalry ensued between
      Casserius and his former mentor as they competed for teaching privileges,
      conflicted on dissection philosophies, and disregarded each other's contributions
      in publications. Tragically, the conflict between these two influential
      anatomists may have overshadowed their contributions to the study of anatomy.
      Casserius was one of the first physicians to develop a comprehensive treatise on
      anatomy. Unfortunately, while Casserius prepared several tracts identifying novel
      structures, he did not live to see his master collection published as he died
      suddenly at the peak of his career in 1616. Interestingly, the English anatomist
      and surgeon John Browne used copies of Casserius' work for his own anatomy text
      and was labeled a plagiarist. It is the contributions from such pioneers as
      Casserius on which we base our current understanding of human anatomy.

PMID- 23959928
TI  - Metoptic canal, duplication of the optic canal and Warwick's foramen in human
      orbits.
AB  - The region of the optic strut is sometimes traversed by some minor canals whose
      incidence and general characteristics have never been studied. As such canals
      could be the route for vessels that could interfere in the surgery of the orbital
      apex, we undertook a detailed anatomical study on a vast collection of dry
      skulls. The examination of 943 dry adult skulls and 360 foetal skulls was carried
      out to precise the anatomy of canals in the optic strut area, their development
      and relationships with the optic canal. A canal traversing the optic strut was
      present in 8.54 % of the orbits. Based on diameter, position within the optic
      strut, and thickness of the bony plate separating it from the optic canal or from
      the superior orbital fissure, the canals piercing the optic strut were classified
      into four types, which include the well-known duplication of the optic canal,
      different aspects of the metoptic canal and a type of canal that to our knowledge
      has never been reported. Warwick's foramen was found in 0.74 % of orbits. The
      area of the optic strut is the frequent site of canals joining the orbit with the
      middle cranial fossa. Some of them can host the ophthalmic artery; others could
      be run by minor vessels which, however, could be the source of annoying bleedings
      in surgical procedures.

PMID- 23959929
TI  - A sciatic nerve with three roots and its perforation by the enlarged ischiadic
      artery.
AB  - Knowledge about the variations of the sciatic nerve (SN) is important for many
      medical science disciplines. Its compression, entrapment or injury of any kind
      can result in loss of sensation, pain or motor disabilities in the lower limbs.
      We observed concurrent neurovascular variations in the gluteal region of an adult
      female cadaver. The SN had three roots as it emerged out of the greater sciatic
      foramen. The upper root passed above the piriformis; the middle and lower roots
      passed below the piriformis. The three roots joined to form the SN in the gluteal
      region. The inferior gluteal artery (IGA) was large, and it passed below the
      piriformis, between the middle and lower root of the SN. After a tortuous course,
      this artery continued down as the sciatic/ischiadic artery. The ischiadic artery
      (IA) was large in size and pierced the SN in the thigh. After piercing the nerve,
      it terminated by dividing into muscular branches. The inferior gluteal nerve
      emerged out from the pelvis through the greater sciatic foramen, above the level
      of the piriformis. The SN in this case was highly predisposed to compression by
      the piriformis, IGA or IA, which in turn may lead to altered cutaneous sensation
      or weakness of the muscles.

PMID- 23959930
TI  - Commentary on: Attention deficit/hyperactivity disorder after neonatal surgery:
      review of the pathophysiology and risk factors.

PMID- 23959931
TI  - Attention deficit/hyperactivity disorder after neonatal surgery: review of the
      pathophysiology and risk factors.
AB  - There are many factors that influence the long-term neurological outcomes in
      children following cardiac surgery. Because there is also complex interaction
      between these many factors, it is difficult to assess which are primary and
      modifiable and which can be used to make improvements in outcomes. As survival
      after complex neonatal heart surgery has increased, the number of children with
      long-term neurological deficits is becoming more evident and this affects quality
      of life for children and their families. One area of long-term assessment is the
      incidence of attention deficit/hyperactivity disorder (ADHD). The incidence rate
      for ADHD following pediatric cardiac surgery is significantly higher than the
      normal rate for children of the same age. Because this is a measureable long-term
      outcome, it can be used to evaluate methods for cerebral protection during
      surgery as well as the timing of surgical procedures to maximize cerebral oxygen
      levels. This paper will review the pathophysiological basis for ADHD in this
      population, based on the similarities between neonatal cardiac surgical patients
      and pre-term infants. Both populations have an increased risk for ADHD and the
      etiology and pathological changes in pre-term infants have been widely
      investigated over the past 25 years. The rate of ADHD in this population is a
      window into the effects of these pathological changes on long-term outcomes.
      Reducing the incidence of ADHD in the future in this population should be a
      primary goal in developing and assessing new cerebral protective strategies
      during cardiac surgery. 

PMID- 23959932
TI  - Advocacy: translating injury research into policy.

PMID- 23959933
TI  - Anthropogenic modification disrupts species co-occurrence in stream
      invertebrates.
AB  - The question of whether species co-occurrence is random or deterministic has
      received considerable attention, but little is known about how anthropogenic
      disturbance mediates the outcomes. By combining experiments, field surveys and
      analysis against null models, we tested the hypothesis that anthropogenic habitat
      modification disrupts species co-occurrence in stream invertebrates across
      spatial scales. Whereas communities in unmodified conditions were structured
      deterministically with significant species segregation, catchment-scale
      conversion to agriculture and sediment deposition at the patch- or micro-habitat
      scale apparently randomized species co-occurrences. This shift from non-random to
      random was mostly independent of species richness, abundance and spatial scale.
      Data on community-wide life-history traits (body size, dispersal ability and
      predatory habits) and beta-diversity indicated that anthropogenic modification
      disrupted community assembly by affecting biotic interactions and, to a lesser
      extent, altering habitat heterogeneity. These data illustrate that the balance
      between predictable and stochastic patterns in communities can reflect
      anthropogenic modifications that not only transcend scales but also change the
      relative forces that determine species coexistence. Research into the effects of
      habitat modification as a key to understanding global change should extend beyond
      species richness and composition to include species co-occurrence, species
      interactions and any functional consequences. 

PMID- 23959934
TI  - New methods for calculating the free energy of charged defects in solid
      electrolytes.
AB  - A methodology for calculating the contribution of charged defects to the
      configurational free energy of an ionic crystal is introduced. The temperature
      independent Wang-Landau Monte Carlo technique is applied to a simple model of a
      solid electrolyte, consisting of charged positive and negative defects on a
      lattice. The electrostatic energy is computed on lattices with periodic boundary
      conditions, and used to calculate the density of states and statistical
      thermodynamic potentials of this system. The free energy as a function of defect
      concentration and temperature is accurately described by a regular solution model
      up to concentrations of 10% of defects, well beyond the range described by the
      ideal solution theory. The approach, supplemented by short-ranged terms in the
      energy, is proposed as an alternative to free energy methods that require a
      number of simulations to be carried out over a range of temperatures. 

PMID- 23959935
TI  - Molecular evolution of kiss2 genes and peptides in vertebrates.
AB  - The kiss1 peptide (kisspeptin), a product of the kiss1 gene, is one of the key
      neuropeptides regulating vertebrate reproduction. In 2009, we identified a
      paralogous gene of kiss1 in the brain of amphibians and named it kiss2.
      Currently, the presence of the kiss2 gene and the kiss2 peptide is still obscure
      in amniotes compared with that in other vertebrates. Therefore, we performed
      genome database analyses in primates and reptiles to investigate the molecular
      evolution of the kiss2 gene in vertebrates. Because the mature kiss2 peptide has
      been identified only in amphibians, we further performed immunoaffinity
      purification and mass spectrometry to identify the mature endogenous kiss2
      peptide in the brains of salmon and turtle that possessed the kiss2 gene. Here we
      provide the first evidence for the presence of a kiss2-like gene in the genome
      database of primates including humans. Synthetic amidated human KISS2 peptide
      activated human GPR54 expressed in COS7 cells, but nonamidated KISS2 peptide was
      inactive. The endogenous amidated kiss2 peptide may not be produced in primates
      because of the lack of an amidation signal in the precursor polypeptide. The
      kiss2-like gene may be nonfunctional in crocodilians because of premature stop
      codons. We identified the mature amidated kiss2 peptide in turtles and fish and
      analyzed the localization of kiss2 peptide mRNA expression in fish. The present
      study suggests that the kiss2 gene may have mutated in primates and crocodilians
      and been lost in birds during the course of evolution. In contrast, the kiss2
      gene and mature kiss2 peptide are present in turtles and fish. 

PMID- 23959936
TI  - Maternal obesity enhances white adipose tissue differentiation and alters genome
      scale DNA methylation in male rat offspring.
AB  - The risk of obesity (OB) in adulthood is strongly influenced by maternal body
      composition. Here we examined the hypothesis that maternal OB influences white
      adipose tissue (WAT) transcriptome and increases propensity for adipogenesis in
      the offspring, prior to the development of OB, using an established model of long
      term metabolic programming. Employing an overfeeding-based rat model, in which
      exposure to OB is limited to preconception and gestation alone, we conducted
      global transcriptomic profiling in WAT, and gene/protein expression analysis of
      lipogenic and adipogenic pathways and examined adipogenic differentiation of WAT
      stromal-vascular cells ex vivo. Using reduced representation bisulfite sequencing
      we also evaluated genome-scale changes in DNA methylation in offspring WAT.
      Maternal OB led to extensive changes in expression of genes (+/- 1.8-fold, P <=
      .05), revealing a distinct up-regulation of lipogenic pathways in WAT. mRNA
      expression of a battery of sterol regulatory element-binding protein-1-regulated
      genes was increased in OB-dam offspring, which were confirmed by immunoblotting.
      In conjunction with lipogenic gene expression, OB-dam offspring showed increased
      glucose transporter-4 mRNA/protein expression and greater AKT phosphorylation
      following acute insulin challenge, suggesting sensitization of insulin signaling
      in WAT. Offspring of OB dams also exhibited increased in vivo expression of
      adipogenic regulators (peroxisome proliferator-activated receptor-gamma, CCAAT
      enhancer binding protein alpha [C/EBP-alpha] and C/EBP-beta), associated with
      greater ex vivo differentiation of WAT stromal-vascular cells. These
      transcriptomic changes were associated with alterations in DNA methylation of CpG
      sites and CGI shores, proximal to developmentally important genes, including key
      pro-adipogenic factors (Zfp423 and C/EBP-beta). Our findings strongly suggest
      that the maternal OB in utero alters adipocyte commitment and differentiation via
      epigenetic mechanisms.

PMID- 23959937
TI  - Restoration of dopamine signaling to the dorsal striatum is sufficient for
      aspects of active maternal behavior in female mice.
AB  - Striatal dopamine (DA) is important for motivated behaviors, including maternal
      behavior. Recent evidence linking the dorsal striatum with goal-directed behavior
      suggests that DA signaling in the dorsal striatum, not just the nucleus
      accumbens, could be involved in maternal behavior. To investigate this question,
      we tested the maternal behavior of mice with DA genetically restricted to the
      dorsal striatum. These mice had a mild deficit in pup retrieval but had normal
      licking/grooming and nursing behavior; consequently, pups were weaned
      successfully. We also tested a separate group of mice with severely depleted DA
      in all striatal areas. They had severe deficits in pup retrieval and
      licking/grooming behavior, whereas nursing behavior was left intact; again, pups
      survived to weaning at normal rates. We conclude that DA signaling in the
      striatum is a part of the circuitry mediating maternal behavior and is
      specifically relevant for active, but not passive, maternal behaviors. In
      addition, DA in the dorsal striatum is sufficient to allow for active maternal
      behavior. 

PMID- 23959938
TI  - Oxidative stress defines the neuroprotective or neurotoxic properties of
      androgens in immortalized female rat dopaminergic neuronal cells.
AB  - Males have a higher risk for developing Parkinson's disease and parkinsonism
      after ischemic stroke than females. Although estrogens have been shown to play a
      neuroprotective role in Parkinson's disease, there is little information on
      androgens' actions on dopamine neurons. In this study, we examined the effects of
      androgens under conditions of oxidative stress to determine whether androgens
      play a neuroprotective or neurotoxic role in dopamine neuronal function.
      Mitochondrial function, cell viability, intracellular calcium levels, and
      mitochondrial calcium influx were examined in response to androgens under both
      nonoxidative and oxidative stress conditions. Briefly, N27 dopaminergic cells
      were exposed to the oxidative stressor, hydrogen peroxide, and physiologically
      relevant levels of testosterone or dihydrotestosterone, applied either before or
      after oxidative stress exposure. Androgens, alone, increased mitochondrial
      function via a calcium-dependent mechanism. Androgen pretreatment protected cells
      from oxidative stress-induced cell death. However, treatment with androgens after
      the oxidative insult increased cell death, and these effects were, in part,
      mediated by calcium influx into the mitochondria. Interestingly, the negative
      effects of androgens were not blocked by either androgen or estrogen receptor
      antagonists. Instead, a putative membrane-associated androgen receptor was
      implicated. Overall, our results indicate that androgens are neuroprotective when
      oxidative stress levels are minimal, but when oxidative stress levels are
      elevated, androgens exacerbate oxidative stress damage. 

PMID- 23959939
TI  - Oral L-arginine stimulates GLP-1 secretion to improve glucose tolerance in male
      mice.
AB  - Pharmacological and surgical interventions that increase glucagon-like peptide 1
      (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes
      mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1
      secretion, particularly in the context of diet-induced obesity, may provide an
      alternative therapeutic approach. Importantly, recent evidence suggests the amino
      acid L-arginine, a well-known insulin secretagogue, can also stimulate release of
      GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral L
      arginine acts as a GLP-1 secretagogue in vivo, to augment postprandial insulin
      secretion and improve glucose tolerance. To test this, we administered L-arginine
      or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in
      lean and diet-induced obese mice. In both lean and obese mice oral L-arginine
      increased plasma GLP-1 and insulin and substantially improved glucose clearance.
      To directly assess the contribution of GLP-1 receptor (GLP-1R)-signaling to these
      improvements, L-arginine was given to Glp1r knockout mice and their wild-type
      littermates. In this experiment oral l-arginine significantly augmented insulin
      secretion and improved glucose clearance in WT mice, but not in Glp1r knockout
      littermates. Taken together these findings identify L-arginine as a GLP-1
      secretagogue in vivo and demonstrate that improvement of glucose tolerance by
      oral L-arginine depends on GLP-1R-signaling. These findings raise the intriguing
      possibility that L-arginine-based nutritional and/or pharmaceutical therapies may
      benefit glucose tolerance by improving the postprandial GLP-1 response in obese
      individuals.

PMID- 23959940
TI  - Kisspeptin, neurokinin B, and dynorphin act in the arcuate nucleus to control
      activity of the GnRH pulse generator in ewes.
AB  - Recent work has led to the hypothesis that kisspeptin/neurokinin B/dynorphin
      (KNDy) neurons in the arcuate nucleus play a key role in GnRH pulse generation,
      with kisspeptin driving GnRH release and neurokinin B (NKB) and dynorphin acting
      as start and stop signals, respectively. In this study, we tested this hypothesis
      by determining the actions, if any, of four neurotransmitters found in KNDy
      neurons (kisspeptin, NKB, dynorphin, and glutamate) on episodic LH secretion
      using local administration of agonists and antagonists to receptors for these
      transmitters in ovariectomized ewes. We also obtained evidence that GnRH
      containing afferents contact KNDy neurons, so we tested the role of two
      components of these afferents: GnRH and orphanin-FQ. Microimplants of a Kiss1r
      antagonist briefly inhibited LH pulses and microinjections of 2 nmol of this
      antagonist produced a modest transitory decrease in LH pulse frequency. An
      antagonist to the NKB receptor also decreased LH pulse frequency, whereas NKB and
      an antagonist to the receptor for dynorphin both increased pulse frequency. In
      contrast, antagonists to GnRH receptors, orphanin-FQ receptors, and the N-methyl
      D-aspartate glutamate receptor had no effect on episodic LH secretion. We thus
      conclude that the KNDy neuropeptides act in the arcuate nucleus to control
      episodic GnRH secretion in the ewe, but afferent input from GnRH neurons to this
      area does not. These data support the proposed roles for NKB and dynorphin within
      the KNDy neural network and raise the possibility that kisspeptin contributes to
      the control of GnRH pulse frequency in addition to its established role as an
      output signal from KNDy neurons that drives GnRH pulses. 

PMID- 23959941
TI  - Association of jacalin-related lectins with wheat responses to stresses revealed
      by transcriptional profiling.
AB  - Jacalin-related lectins (JRLs) are carbohydrate-binding proteins widely present
      in plants and have one or more jacalin domains in common. However, JRLs'
      structural types and functions are still poorly understood. In the present study,
      a total of 67 wheat (Triticum aestivum) JRL genes were identified through an
      exhausted search of EST database coupling with genome walking using published 454
      sequence reads of Chinese Spring. A comparison of the translated wheat JRL
      proteins with those from other plants showed plant JRLs generally had low
      sequence similarity within and between species but exhibited conserved modular
      domain structures. More JRL genes encoded multiple jacalin domains in Arabidopsis
      thaliana, whereas more genes encoded chimeric JRLs in cereal plants. Dirigent
      domain-containing JRL genes were Poaceae-specific and accounted for nearly half
      of the identified wheat JRL genes. The dirigent domains were evolutionarily
      significantly correlated with the covalently linked jacalin domains. A
      phylogenetic analysis showed JRL proteins have experienced a substantial
      diversification after speciation. Moreover, new structural features conserved
      across the taxa were identified. Digital expression analysis and RT-PCR assays
      showed the expression of wheat JRL genes was largely tissue specific, typically
      low, and mostly inducible by biotic and abiotic stresses and stress hormones.
      These results suggest plant JRLs are critical for plant adaptation to stressful
      environments.

PMID- 23959942
TI  - Reply: To PMID 22576353.

PMID- 23959943
TI  - Stability of kinetochore-microtubule attachment and the role of different KMN
      network components in Drosophila.
AB  - Kinetochores bind spindle microtubules and also act as signaling centers that
      monitor this interaction. Defects in kinetochore assembly lead to chromosome
      missegregation and aneuploidy. The interaction between microtubules and
      chromosomes involves a conserved super-complex of proteins, known as the
      KNL1Mis12Ndc80 (KMN) network, composed by the KNL1 (Spc105), Mis12, and Ndc80
      complexes. Previous studies indicate that all components of the network are
      required for kinetochore-microtubule attachment and all play relevant functions
      in chromosome congression, biorientation, and segregation. Here, we report a
      comparative study addressing the role of the different KMN components using dsRNA
      and in vivo fluorescence microscopy in Drosophila S2 cells allowing us to suggest
      that different KMN network components might perform different roles in chromosome
      segregation and the mitotic checkpoint signaling. Depletion of different
      components results in mostly lateral kinetochore-microtubule attachments that are
      relatively stable on depletion of Mis12 or Ndc80 but very unstable after Spc105
      depletion. In vivo analysis on depletion of Mis12, Ndc80, and to some extent
      Spc105, shows that lateral kinetochore-microtubule interactions are still
      functional allowing poleward kinetochore movement. We also find that different
      KMN network components affect differently the localization of spindle assembly
      checkpoint (SAC) proteins at kinetochores. Depletion of Ndc80 and Spc105
      abolishes the mitotic checkpoint, whereas depletion of Mis12 causes a delay in
      mitotic progression. Taken together, our results suggest that Mis12 and Ndc80
      complexes help to properly orient microtubule attachment, whereas Spc105 plays a
      predominant role in the kinetochore-microtubule attachment as well as in the
      poleward movement of chromosomes, SAC response, and cell viability.

PMID- 23959944
TI  - Reproducibility of 6- and 4-category faces pain scale to the assessment of
      temporomandibular joint pain and muscle in school-age children.
AB  - OBJECTIVE: The aim of this study was to compare the levels of reproducibility
      between two Faces Pain Scales (FPS) of 6 and 4 categories to the assessment of
      pain intensity on children with and without Temporomandibular joint and muscle
      pain. MATERIAL AND METHODS: A total of 29 children were recruited: 13 symptomatic
      (9.79 +/- 1.36 years old) and 16 asymptomatic (8.69 +/- 0.87 years old). One
      previously-trained examiner applied manual palpation to evaluate orofacial
      structures, and FPS to assess pain intensity. All children were initial evaluated
      using 6-category FPS and after 3 days using 4-category FPS. The children were
      assessed after a seven day time interval from initial and second sessions.
      Weighted Kappa coefficient was used to verify reproducibility levels. RESULTS:
      Similar levels of reproducibility (moderate and fair kappa values) have been
      verified with the application of the 6-category FPS on symptomatic and
      asymptomatic children. Similar results were verified using 4-category FPS on
      symptomatic and asymptomatic children (poor and fair kappa values). CONCLUSION:
      Higher levels of reproducibility were verified with the application of the 6
      category FPS in both groups and considering symptomatic and asymptomatic as
      single group. In this way, the 6-category FPS should be preferred over the 4
      category FPS to assess pain intensity on children's orofacial structures.

PMID- 23959946
TI  - Detection of high-risk human papillomaviruses in fresh breast cancer samples
      using the hybrid capture 2 assay.
AB  - The etiology of breast cancer remains unknown and the role of human
      papillomavirus (HPV) in breast carcinogenesis is controversial. This study
      investigated the prevalence of high-risk HPV infections in Chinese women with
      breast cancer and the possible relationship between high-risk HPV infection and
      the clinicopathological characteristics of breast cancer. Tumor cells from 224
      fresh breast cancer samples and 37 fresh breast fibroadenomas were collected for
      hybrid capture 2 (HC2) assay. HC2 was the only technique approved by the United
      States Food and Drug Administration for screening for high-risk HPV infection in
      2008. The prevalence of high-risk HPV infection in breast cancer samples was
      21.4%, which was slightly higher than the 16.2% observed in breast fibroadenomas.
      Age and menopausal status were not risk factors for high-risk HPV infection among
      breast cancer patients. The clinical and pathological characteristics of breast
      cancer showed no significant correlation with high-risk HPV infection. Although
      the prevalence of 13 subtypes of high-risk HPV infections was similar in breast
      cancer and nonmalignant breast samples, the presence of high-risk HPVs in both
      malignant and benign breast samples implies that a possible causal role in breast
      cancer carcinogenesis could not be ruled out. Clarifying the possible link
      between high-risk HPVs and breast cancer might benefit women vaccinated against
      HPV and could decrease the incidence of HPV-related breast cancer.

PMID- 23959947
TI  - A single nucleotide polymorphism on the GALNT14 gene as an effective predictor of
      response to chemotherapy in advanced hepatocellular carcinoma.
AB  - Previously, a pilot genome-wide association study has identified candidate single
      nucleotide polymorphism predictors for the therapeutic response of 5
      fluorouracil, mitoxantrone and cisplatin (FMP) combination chemotherapy in
      advanced hepatocellular carcinoma (HCC). Here, we conducted a prospective
      confirmatory study to examine the predictive value of rs9679162 (located on
      GALNT14 gene) for the therapeutic responses using a split-dose FMP protocol. One
      hundred and seven advanced HCC patients receiving split-dose FMP therapy were
      enrolled. All patients were in Barcelona Clinical Liver Cancer Stage C with
      either main portal vein thrombosis and/or distant metastasis. Of them, 105
      (98.1%) were Child-Pugh classification B. GALNT14 genotype was determined before
      therapy. Of the patients included, 28 were rs9679162 "TT" and 79 were "non-TT"
      ("GG" + "GT") genotype. The median overall survival, time-to-progression,
      response rate and disease control rate were ("TT" versus "non-TT") 6.8 versus 3.9
      months (p < 0.001), 3.9 versus 2.1 months (p < 0.001), 28.6% versus 10.1% (p =
      0.029) and 35.7% versus 15.2% (p = 0.030), respectively. Multivariate analysis
      indicated that rs9679162 genotype was an independent predictor for overall
      survival (p = 0.002). Categorical analysis showed that 17 patients with "TT"
      genotype, tumor size < 10 cm and neutrophils < 74% had a median overall survival
      of 25.5 months and a therapeutic response rate of 47.1%. In conclusion, this
      prospective study confirmed that GALN14 genotype (rs9679162) was an effective
      predictor for therapeutic outcome in advanced HCC patients treated by FMP
      chemotherapy. Combining GALNT14 genotype and clinical parameters, a subgroup of
      patients with excellent outcome was identified. 

PMID- 23959948
TI  - Wormian bones: a review.
AB  - Wormian bones are abnormal ossicles that develop from extra ossification centers
      within the cranium. They are most frequently located in the lambdoid suture or
      the coronal suture, and have been seen in the fontanelles, particularly the
      posterior fontanelle. It is unclear at this time exactly how or why they are
      formed, although genetic as well as environmental factors have been proposed.
      Their initial formation is thought to be caused by a degree of dural strain and
      increased sutural width. These conditions can result from mechanically induced
      stress due to intentional deformation like that practiced in ancient cultures,
      premature sutural closure, or from reduced skull ossification as seen in
      metabolic bone diseases. The cause of the malformation can have an influence on
      the number and location of Wormian bones. Clinically, Wormian bones are used as
      markers in the diagnoses of many autosomal dominant genetic disorders, namely,
      craniosynostosis and osteogenesis imperfecta.

PMID- 23959950
TI  - A coral reef refuge in the Red Sea.
AB  - The stability and persistence of coral reefs in the decades to come is uncertain
      due to global warming and repeated bleaching events that will lead to reduced
      resilience of these ecological and socio-economically important ecosystems.
      Identifying key refugia is potentially important for future conservation actions.
      We suggest that the Gulf of Aqaba (GoA) (Red Sea) may serve as a reef refugium
      due to a unique suite of environmental conditions. Our hypothesis is based on
      experimental detection of an exceptionally high bleaching threshold of northern
      Red Sea corals and on the potential dispersal of coral planulae larvae through a
      selective thermal barrier estimated using an ocean model. We propose that
      millennia of natural selection in the form of a thermal barrier at the
      southernmost end of the Red Sea have selected coral genotypes that are less
      susceptible to thermal stress in the northern Red Sea, delaying bleaching events
      in the GoA by at least a century. 

PMID- 23959949
TI  - Signaling pathways involved in 1-octen-3-ol-mediated neurotoxicity in Drosophila
      melanogaster: implication in Parkinson's disease.
AB  - Previously, we have pioneered Drosophila melanogaster as a reductionist model to
      show that 1-octen-3-ol, a musty-smelling volatile compound emitted by fungi and
      other organisms, causes loss of dopaminergic neurons and Parkinson's disease-like
      symptoms in flies. Using our in vivo Drosophila system, the modulatory roles of
      important signaling pathways-JNK, Akt and the caspase-3-dependent apoptotic
      pathway were investigated in the context of 1-octen-3-ol-induced dopamine
      neurotoxicity. When heterozygous flies carrying mutant alleles for these proteins
      were exposed to 0.5 ppm of 1-octen-3-ol, they had shorter survival times than
      wild-type Drosophila. The overexpressed levels of wild-type JNK and Akt, (UAS-bsk
      and UAS-Akt) with TH-GAL4 and elav-GAL4 drivers improved the survival duration of
      exposed flies compared with controls. Thus, we found that Akt and JNK both
      protect against loss of dopamine activity associated with 1-octen-3-ol exposure,
      indicating the pro-survival role of these signaling pathways. Further, 1-octen-3
      ol exposure was associated with activation of caspase 3, a hallmark for
      apoptosis.

PMID- 23959951
TI  - Effects of nicotine on cardiovascular remodeling in a mouse model of systemic
      hypertension.
AB  - Usage of nicotine-only formulations, such as transdermal patches, nicotine gum,
      or electronic nicotine delivery systems is increasing, as they are perceived as
      healthier alternatives to traditional cigarettes. Unfortunately, there is little
      data available on the effect of isolated nicotine on myocardial and aortic
      remodeling, especially in the setting of cardiovascular disease risk factors,
      such as hypertension. We hypothesized that nicotine would exacerbate
      cardiovascular remodeling induced by angiotensin-II (Ang II) treatment.
      Subcutaneous osmotic minipumps were implanted to administer Ang II, Nic, nicotine
      plus Ang II or saline to C57Bl/6 mice for 4 weeks. Heart weights were increased
      by all treatments, with control < nicotine < Ang II < nicotine + Ang II. Activity
      levels of matrix metalloproteinase-2 mirrored these changes and demonstrated
      clear additivity between nicotine and Ang II. Histopathological analysis of
      aortas revealed that mice receiving combined nicotine and Ang II treatment
      induced significant hypertrophy compared to all other groups. This study reveals
      possible cardiotoxic interactions between nicotine and a common model of systemic
      hypertension. Safety testing of novel nicotine delivery devices should consider
      that hypertension is a common impetus to begin smoking cessation therapy, and
      potential interactions should be more thoroughly studied.

PMID- 23959953
TI  - Characterization of Atg8 in lepidopteran insect cells.
AB  - Yeast Atg8 and mammalian microtubule-associated protein light chain 3 (LC3) are
      landmark proteins essential for autophagy. Here the lepidopteran Atg8, a homolog
      of LC3, is characterized. Sequence analysis reveals that Atg8 proteins are highly
      conserved in lepidopteran species. The abundance of endogeous Atg8 and the ratios
      of Atg8 conjugation to phosphatidylethanolamine (Atg8-PE)/Atg8 are different
      among several lepidopteran cell lines and different tissues of Helicoverpa
      armigera larvae. Both the density of fluorescent pre-autophagosomal structures
      with GFP-Ha Atg8 and the abundance of Atg6 are positively correlated with levels
      of Atg8-PE in different cell lines. The mutant GFP-Atg8(G116A) has lost the
      function in punctual formation, suggesting that G116 is important for autophagy.
      Exogenous factors have significant influences on the conversion of Atg8 in
      lepidopteran cells. Bacillus thuringiensis enhances the degradation of Atg8 in
      Spodoptera litura Sl-HP cells. Atg8-PE degrades gradually with extension of amino
      acid starvation, and bafilomycin A1 can block the decrease through the inhibition
      of autophagosome fusion with lysosome. Interestingly, high pH is more effective
      than amino acid starvation in Bombyx mori Bme cells to induce the conversion of
      BmAtg8 to BmAgt8-PE. Change of the quality of fetal bovine serum in the culture
      medium results in alteration of the ratio of Atg8-PE/Atg8 in some lepidopteran
      cell lines. 

PMID- 23959954
TI  - Role of plasma BNP in patients with ascites: advantages and pitfalls.

PMID- 23959952
TI  - Impact of bullying in childhood on adult health, wealth, crime, and social
      outcomes.
AB  - Bullying is a serious problem for schools, parents, and public-policymakers
      alike. Bullying creates risks of health and social problems in childhood, but it
      is unclear if such risks extend into adulthood. A large cohort of children was
      assessed for bullying involvement in childhood and then followed up in young
      adulthood in an assessment of health, risky or illegal behavior, wealth, and
      social relationships. Victims of childhood bullying, including those that bullied
      others (bully-victims), were at increased risk of poor health, wealth, and social
      relationship outcomes in adulthood even after we controlled for family hardship
      and childhood psychiatric disorders. In contrast, pure bullies were not at
      increased risk of poor outcomes in adulthood once other family and childhood risk
      factors were taken into account. Being bullied is not a harmless rite of passage
      but throws a long shadow over affected people's lives. Interventions in childhood
      are likely to reduce long-term health and social costs. 

PMID- 23959955
TI  - Improving health system quality in low- and middle-income countries that are
      expanding health coverage: a framework for insurance.
AB  - PURPOSE: Low- and middle-income countries are increasingly pursuing health
      financing reforms aimed at achieving universal health coverage. As these
      countries rapidly expand access to care, overburdened health systems may fail to
      deliver high-quality care, resulting in poor health outcomes. Public insurers
      responsible for financing coverage expansions have the financial leverage to
      influence the quality of care and can benefit from guidance to execute a cohesive
      health-care quality strategy. DATA SOURCES: and selection Following a literature
      review, we used a cascading expert consultation and validation process to develop
      a conceptual framework for insurance-driven quality improvements in health care.
      RESULTS OF DATA SYNTHESIS: The framework presents the strategies available to
      insurers to influence the quality of care within three domains: ensuring a basic
      standard of quality, motivating providers and professionals to improve, and
      activating patient and public demand for quality. By being sensitive to the local
      context, building will among key stakeholders and selecting context-appropriate
      ideas for improvement, insurers can influence the quality through four possible
      mechanisms: selective contracting; provider payment systems; benefit package
      design and investments in systems, patients and providers. CONCLUSION: This
      framework is a resource for public insurers that are responsible for rapidly
      expanding access to care, as it places the mechanisms that insurers directly
      control within the context of broader strategies of improving health-care
      quality. The framework bridges the existing gap in the literature between broad
      frameworks for strategy design for system improvement and narrower discussions of
      the technical methods by which payers directly influence the quality.

PMID- 23959956
TI  - Hyperglycaemia-induced chemoresistance of prostate cancer cells due to IGFBP2.
AB  - Clinically relevant prostate cancer (PCa) is more frequent in Westernised
      societies and increasingly men have co-morbidities associated with a Western
      lifestyle, primarily diabetes, characterised by hyperinsulinaemia and
      hyperglycaemia. IGFs and their binding proteins (IGFBPs) are important mediators
      of the effects of nutrition on growth and play a key role in the development of
      PCa. We used DU145, PC3 and LNCaP PCa cell lines to examine how hyperglycaemia
      altered their response to docetaxel. Trypan Blue dye-exclusion assay was used to
      determine the percentage of cell death. Protein abundance was determined using
      western immunoblotting. Levels of IGFBP2 were measured using an ELISA. IGFBP2
      gene silencing was achieved using siRNA technology. DNA methylation was assessed
      using combined bisulphide restriction analysis. Acetylation status of histones H3
      and H4 associated with IGFBP2 gene was assessed using chromatin
      immunoprecipitation assay. Hyperglycaemia reduced docetaxel-induced apoptosis by
      40% for DU145 cells and by 88% for LNCaP cells. This reduced cell death was
      mediated by a glucose-induced up-regulation of IGFBP2, as silencing IGFBP2
      negated the survival effect of high glucose. Glucose increased IGFBP2 via
      increasing the acetylation of histones associated with the IGFBP2 gene promoter.
      This finding could have important implications in relation to therapeutic
      strategies as epigenetic modulation could be reversible.

PMID- 23959957
TI  - Developmental changes in ciliary motility on choroid plexus epithelial cells
      during the perinatal period.
AB  - Cilia have crucial roles in various developmental and physiological events.
      Previously, we reported that choroid plexus epithelial cells (CPECs) have
      multiple, nonmotile 9+0 cilia, but the cilia exhibit transient motility with
      variable axonemal arrangements in the neonatal period. These features make these
      cilia unique, as they do not fit in to the traditional categories of primary or
      motile cilia, and their physiological roles remain elusive. To address this
      issue, we studied ciliary motility on CPECs through development, with particular
      interest in the embryonic period. In the fetal choroid plexus of the lateral
      ventricles, the proportion of cells with motile cilia and their beat frequency
      increased over time. The ciliary motility profiles peaked near the day of birth,
      and gradually declined in the two weeks thereafter. The dynamic changes in
      ciliary motility correlated with changes in Dnahc11 expression. We demonstrated
      previously that the ciliary motility at P2 was insufficient to produce detectable
      fluid flow; thus it appears that CPEC cilia do not produce fluid flow at any
      point during development. Together, our results suggest that a temporally
      regulated, unique function of CPEC cilia may exist during the perinatal period.

PMID- 23959958
TI  - Cortisol profile and depressive symptoms in older adults residing in Brazil and
      in Canada.
AB  - BACKGROUND AND AIM: How cortisol, a stress biological marker, differs according
      to depressive symptoms has mostly been examined in high-income countries.
      Including low- and middle-income countries in research on this matter would allow
      examining a wider range of exposure to adversity and improving the estimates of
      the associations between diurnal cortisol and depression. The aim of this study
      is to compare the profile of diurnal cortisol and depressive symptoms in 65- to
      74-year-old residents of Santa Cruz (in an underdeveloped region, northeast
      Brazil, n = 64) and Saint-Bruno (a suburban area, QC, Canada, n = 60). METHODS:
      Home interviews included assessments of socioeconomic variables, health
      behaviors, depressive symptoms (Center for Epidemiologic Studies Depression
      Scale, CES-D) and Cortisol Awakening Response (CAR: awakening, 30, 60 min
      afterward), and at 1500 hours and bedtime from saliva collected over 2 days.
      Mixed linear models were used to estimate the associations between diurnal
      cortisol and depressive symptoms. RESULTS: Santa Cruz residents had lower
      cortisol levels upon awakening (beta = -1.24, p = 0.04) and elevated bedtime
      levels (beta = 20.29, p < 0.001) indicating chronic stress compared to Saint
      Bruno residents. Elevated depressive symptoms were associated with a blunted CAR
      (flatter slope, indicative of chronic stress) in Santa Cruz residents (beta = 
      0.19, p = 0.04), while greater diurnal cortisol levels (larger area under the
      curve), indicative of moderate stress, were observed in Saint-Bruno residents
      (beta = 1.96, p = 0.047). CONCLUSION: Adverse living conditions in this remote
      area of Brazil may lead to a state of chronic stress and a different relationship
      with elevated depressive symptoms from persons aging in a Canadian suburban area.

PMID- 23959959
TI  - C-reactive protein is independently associated with coronary atherosclerosis
      burden among octogenarians.
AB  - AIM OF THE STUDY: In contrast to the general population, individuals with
      primarily persistent elevation of inflammatory activity display a significant
      association between inflammatory biomarkers and atherosclerotic burden. In older
      individuals, immunosenescence upregulates the innate response and, by this way,
      may hypothetically favor the presence of this association. The aim of this study
      was to evaluate this hypothesis in healthy octogenarians. METHODS: Participants
      (n = 208) aged 80 years or older, asymptomatic and without medical and laboratory
      evidence of chronic diseases or use of anti-inflammatory treatments were included
      in the study. Lipid profile and plasma C-reactive protein (CRP) were measured at
      baseline and cardiac computed tomography was performed within 1-week interval for
      measuring coronary calcium score (CCS). RESULTS: The median plasma CRP was 1.9
      mg/L (1.0-3.4) and 33 % of the participants had elevated CRP defined as C3 mg/L.
      Among those with high CRP, there was an increased frequency of high CCS (C100) as
      compared with their counterparts (71 vs 50 %, p = 0.001). The association between
      CRP and CCS persisted even after adjustment for age, sex, cardiovascular risk
      factors and statin therapy. The area under the receiver-operating curve for CRP
      was 0.606 using CCS C100 as a binary outcome. The sensitivities for CCS C100 were
      40 and 74 % for the cutoff points of CRP C3 or 1 mg/L, respectively. CONCLUSION:
      The present study was able to confirm that in very elderly individuals, systemic
      inflammatory activity is independently associated with coronary atherosclerosis
      burden.

PMID- 23959960
TI  - Efficacy and safety of insulin lispro in geriatric patients with type 2 diabetes:
      a retrospective analysis of seven randomized controlled clinical trials.
AB  - BACKGROUND AND AIMS: Glycemic control in geriatric patients with type 2 diabetes
      (T2DM) remains clinically challenging. The objective of this study was to compare
      the safety and efficacy of insulin lispro in patients C65 years (geriatric) to
      those?65 years (non-geriatric), using a metaanalysis of randomized controlled
      clinical trials (RCT). METHODS: This is a retrospective analysis of predefined
      endpoints from an integrated database of seven RCTs of T2DM patients treated with
      insulin lispro. The primary efficacy measure tested the non-inferiority of
      insulin lispro (geriatric vs. non-geriatric; non-inferiority margin 0.4 %) in
      terms of hemoglobin A1c (HbA1c) change from baseline to Month 3 (N = 1,525), with
      change from baseline to Month 6 as a supportive analysis (N = 885). Changes in
      HbA1c from baseline were evaluated with an analysis of covariance model.
      Secondary measures included incidence and rate of hypoglycemia, and incidence of
      cardiovascular events. RESULTS: Mean change in HbA1c from baseline to Month 3 was
      similar for geriatric (-0.97 %) and non-geriatric patients (-1.05 %); least
      square (LS) mean difference (95 % CI) was 0.02 % (-0.11, 0.15 %; p = 0.756).
      Similar results were observed in patients treated up to Month 6; LS mean
      difference (95 % CI) was 0.07 % (-0.12, 0.26 %; p = 0.490). Decrease in HbA1c
      from baseline to Months 3 and 6 was non-inferior in geriatric compared with non
      geriatric patients. There were no significant differences in the incidence and
      the rate of hypoglycemia, incidence of cardiovascular events, or other serious
      adverse events including malignancy, post-baseline between the two cohorts.
      CONCLUSION: Key measures of efficacy and safety in geriatric patients with T2DM
      were not significantly different from non-geriatric patients when utilizing
      insulin lispro. Insulin lispro may be considered a safe and efficacious
      therapeutic option for the management of T2DM in geriatric patients.

PMID- 23959961
TI  - Resistance training improves single leg stance performance in older adults.
AB  - Age-associated losses in muscle mass, or sarcopenia, are marked by accompanying
      decrements in strength and muscle quality, impairing balance and increasing the
      risk for falls. Although progressive resistance training has been widely accepted
      as an appropriate modality for the treatment of sarcopenia, it has yet to offer
      consistent results in terms of improved balance. The purpose of the present
      research was to investigate the effects on static balance performance following a
      6-week full-body progressive resistance training program in untrained older
      adults. Evaluation of magnitude-based inferences indicated the progressive
      resistance training intervention to be likely beneficial for improving static
      balance performance. These results were likely related to the strengthening of
      all major muscle groups by the incorporation of both free weights and resistance
      machines in the exercise regimen. Our findings support the use of progressive
      resistance training for untrained older adults to improve balance.

PMID- 23959962
TI  - Robust revascularization, despite impaired VEGF production, after meniscus
      allograft transplantation in rabbits.
AB  - BACKGROUND: Little is known about vascularization restoration and vascular
      circulation after allogenic graft transplantation, which are both important
      prerequisites for optimal use of allograft meniscus transplantation. PURPOSE: To
      study vascularization restoration through autograft and allograft meniscus models
      in Oryctolagus cuniculus. STUDY DESIGN: Controlled laboratory study. METHODS:
      Forty-eight rabbits at mature bone age were randomized to receive either an
      autograft or allograft after the meniscus of the left knee was completely
      resected. Vascularization, blood circulation, histological characteristics of the
      grafted meniscus and surrounding tissues, and vascular endothelial growth factor
      (VEGF) expression in the meniscus were assessed at 4, 8, and 12 weeks after
      allograft or autologous transplantation. RESULTS: The grafted meniscus was in
      good condition and was well connected to the surrounding joint capsule, and no
      obvious damage of the joint cartilage at the tibial plateau was observed. Even
      though the revascularization pattern was similar in the 2 groups, the meniscus
      body showed vessel growth mainly at the adhesion margin for less than one-third
      of the meniscus transverse diameter, and no significant vascular distribution was
      found at the free margin. Blood circulation peaked after 8 weeks at the anterior
      and posterior horns and declined thereafter. This was mimicked by VEGF
      expression, which showed a progressive decrease with time, even though the
      vascular endothelial cells gradually increased over time. There were no
      statistical differences in the various assessments between the allograft and
      autograft groups. CONCLUSION: At 12 weeks after meniscus allografting, the
      vascular circulation had almost recovered and gradual reconstruction of cells and
      fibers had begun, mimicking similar observations in the autograft group. CLINICAL
      RELEVANCE: Our data provide test reference for clinical rehabilitation after
      meniscus autograft.

PMID- 23959963
TI  - Concussion symptoms and neurocognitive performance of high school and college
      athletes who incur multiple concussions.
AB  - BACKGROUND: Multiple concussions have been associated with prolonged symptoms,
      recovery time, and risk for future concussions. However, very few studies have
      examined the effect of multiple concussions on neurocognitive performance and the
      recently revised symptom clusters using a large database. PURPOSE: To examine
      concussed athletes with a history of 0, 1, 2, or >=3 concussions on
      neurocognitive performance and the recently revised symptom clusters. STUDY
      DESIGN: Cohort study (prognosis); Level of evidence, 2. METHODS: The independent
      variables were concussion group (0, 1, 2, and >=3 concussions) and time
      (baseline, 3 days, and 8 days). The dependent variables were neurocognitive test
      scores as measured by the Immediate Post-Concussion Assessment and Cognitive
      Testing (ImPACT) neurocognitive test battery (verbal and visual memory,
      processing speed, and reaction time) and 4 concussion symptom clusters (migraine
      cognitive-fatigue, affective, somatic, and sleep). All concussed athletes (n =
      596) were administered the ImPACT test at a mean 2.67 +/- 1.98 and 7.95 +/- 4.46
      days after injury. A series of 4 (concussion group) * 3 (time) repeated-measures
      analyses of covariance (age = covariate) were performed on ImPACT composite
      scores and symptom clusters. RESULTS: Concussed athletes with >=3 concussions
      were still impaired 8 days after a concussion compared with baseline scores on
      verbal memory (P < .001), reaction time (P < .001), and migraine-cognitive
      fatigue symptoms (P < .001). There were no significant findings on the remaining
      dependent variables. CONCLUSION: Concussed athletes with a history of >=3
      concussions take longer to recover than athletes with 1 or no previous
      concussion. Future research should concentrate on validating the new symptom
      clusters on multiple concussed athletes, examining longer recovery times (ie, >8
      days) among athletes with multiple concussions.

PMID- 23959964
TI  - Elevation in circulating biomarkers of cartilage damage and inflammation in
      athletes with femoroacetabular impingement.
AB  - BACKGROUND: Femoroacetabular impingement (FAI) is one of the most common causes
      of early cartilage and labral damage in the nondysplastic hip. Biomarkers of
      cartilage degradation and inflammation are associated with osteoarthritis. It was
      not known whether patients with FAI have elevated levels of biomarkers of
      cartilage degradation and inflammation. HYPOTHESIS: Compared with athletes
      without FAI, athletes with FAI would have elevated levels of the inflammatory C
      reactive protein (CRP) and cartilage oligomeric matrix protein (COMP), a
      cartilage degradation marker. STUDY DESIGN: Controlled laboratory study. METHODS:
      Male athletes with radiographically confirmed FAI (n = 10) were compared with
      male athletes with radiographically normal hips with no evidence of FAI or hip
      dysplasia (n = 19). Plasma levels of COMP and CRP were measured, and subjects
      also completed the Short Form-12 (SF-12) and Hip Disability and Osteoarthritis
      Outcome Score (HOOS) surveys. RESULTS: Compared with controls, athletes with FAI
      had a 24% increase in COMP levels and a 276% increase in CRP levels as well as a
      22% decrease in SF-12 physical component scores and decreases in all of the HOOS
      subscale scores. CONCLUSION: Athletes with FAI demonstrate early biochemical
      signs of increased cartilage turnover and systemic inflammation. CLINICAL
      RELEVANCE: Chondral injury secondary to the repetitive microtrauma of FAI might
      be reliably detected with biomarkers. In the future, these biomarkers might be
      used as screening tools to identify at-risk patients and assess the efficacy of
      therapeutic interventions such as hip preservation surgery in altering the
      natural history and progression to osteoarthritis.

PMID- 23959965
TI  - Progression of osteoarthritis after double- and single-bundle anterior cruciate
      ligament reconstruction.
AB  - BACKGROUND: No consensus has been reached on the advantages of double-bundle (DB)
      anterior cruciate ligament reconstruction (ACLR) over the single-bundle (SB)
      technique, particularly with respect to the prevention of osteoarthritis (OA)
      after ACLR. PURPOSE: To evaluate whether DB ACLR has any advantages in the
      prevention of OA or provides better stability and function after ACLR compared
      with the SB technique. STUDY DESIGN: Randomized controlled trial; Level of
      evidence, 2. METHODS: A total of 130 patients with an ACL injury in one knee were
      prospectively randomized into a DB group (n = 65) or an SB group (n = 65). For
      the radiologic evaluation, we determined the degree of OA based on the Kellgren
      Lawrence grade before the operation and at the time of the final follow-up and
      determined the number of patients with progression of OA more than one grade from
      pre- to postoperation. We evaluated the stability results using the Lachman and
      pivot-shift tests and stress radiography. We also compared the functional
      outcomes based on the Lysholm knee score, Tegner activity score, and
      International Knee Documentation Committee (IKDC) subjective scale. RESULTS: Six
      patients (4 in the DB group and 2 in the SB group) suffered graft failure during
      the follow-up and had ACL revision surgery (P = .06). A total of 112 patients
      were observed for a minimum of 4 years (DB group, n = 52; SB group, n = 60). Five
      patients (9.6%) in the DB group and 6 patients (10%) in the SB group had more
      advanced OA at the final follow-up (P = .75). All patients recovered full range
      of motion within 6 months from surgery. Stability results of the Lachman test,
      pivot-shift test, and the radiographic stability test failed to reveal any
      significant intergroup differences (P = .37, .27, and .67, respectively). In the
      pivot-shift result, the DB group had 4 patients with grade 2 and the SB group had
      3 patients with grade 2 (P = .27). Clinical outcomes, including Lysholm knee and
      Tegner activity scores, were similar in the 2 groups. Statistical significance
      was achieved only for the IKDC subjective scale (78.2 in DB group vs 73.1 in SB
      group; P = .03). CONCLUSION: The DB technique, compared with SB, was not more
      effective in preventing OA and did not have a more favorable failure rate.
      Although the DB ACLR technique produced a better IKDC subjective scale result
      than did the SB ACLR technique, the 2 modalities were similar in terms of
      clinical outcomes and stability after a minimum 4 years of follow-up.

PMID- 23959966
TI  - Testicular cancer and viral infections: a systematic literature review and meta
      analysis.
AB  - In 1984, Newell and coworkers were the first to suggest that testicular cancer
      might have a viral etiology since it showed similar characteristics to Hodgkin's
      lymphoma. A systematic literature review and meta-analysis was conducted to
      investigate a possible association between viral infections (EBV, CMV, Parvovirus
      B19, HPV, and HIV) and testicular cancer. Articles published from 1985 through
      June 2010 were located from MEDLINE and EMBASE databases, 21 articles were
      finally included in the review. For infection with EBV, CMV, Parvovirus B19, and
      HIV the pooled OR were 4.80 (95% CI 0.98-23.54), 1.85 (95% CI 0.92-3.70), 2.86
      (95% CI 0.35-23.17), and 1.79 (95% CI 1.45-2.21) respectively. No pooling was
      possible for HPV infection studies due to small numbers. The results support a
      possible association, but more epidemiological studies with better viral
      identification and localization methods are needed to verify these findings.

PMID- 23959967
TI  - Noroviruses and histo-blood groups: the impact of common host genetic
      polymorphisms on virus transmission and evolution.
AB  - Noroviruses (NoVs) are recognized as a leading cause of human gastroenteritis
      worldwide. Infection occurs following the ingestion of contaminated food or, most
      often, through direct contact from person to person. However, not all individuals
      are equally sensitive to these viruses. Indeed, NoVs use glycans of the ABH and
      Lewis histo-blood group antigen family (HBGAs) as attachment factors. At the
      epithelial level, the synthesis of these HBGAs requires the action of several
      glycosyltransferases that are encoded by the ABO, FUT2, and FUT3 genes. The
      combined polymorphism at these three loci dictates sensitivity to NoV infection
      because the attachment profile to these glycans varies among strains. Structural
      analysis of the capsid protein interaction with HBGAs reveals distinct modes of
      binding for strains of genogroups I and II but high conservation within each
      genogroup, whereas minor amino acid changes are sufficient to generate
      modifications of HBGA-binding specificities or affinities. Such modifications
      therefore induce changes in the spectrum of susceptible individuals. Studies of
      NoV-HBGA interactions together with phylogenetic analyses and the epidemiologic
      survey of strains indicate that NoV transmission and evolution depend on both the
      establishment of herd immunity and the genetic resistance of many individuals,
      which confers herd innate protection by restricting NoV circulation.

PMID- 23959968
TI  - Long common bile duct stricture: wait, are we on the right track?

PMID- 23959969
TI  - The tori of the mouth and ear: a review.
AB  - There is a great deal of literature regarding the tori of the mouth and ear.
      However, there is controversy regarding the etiology and prevalence of each. The
      torus palatinus is generally agreed to be the most common oral exostosis and is
      more frequently found in females. The torus mandibularis is also quite common, is
      more prevalent in males, and occurs bilaterally in 80% of cases. Far less data
      have been presented regarding the torus maxillaries primarily due to the lack of
      consensus regarding its nomenclature and classification. These oral tori are
      thought to be inherited in an autosomal dominant manner with a relatively high
      penetrance; however, environmental and functional factors have been postulated
      that may account for a more complex etiology than simply genetics. The torus
      auditivus is rarely acknowledged in clinical papers and most data are found in
      anthropological journals. Although there is an abundance of literature that
      addresses these traits individually, there is a lack of research that
      collectively acknowledges these. Therefore, the aim of this study was to present
      a composite review of the tori with regards to their anatomical features,
      prevalence, etiology and clinical relevance.

PMID- 23959970
TI  - Testing simulations of intra- and inter-annual variation in the plant production
      response to elevated CO(2) against measurements from an 11-year FACE experiment
      on grazed pasture.
AB  - Ecosystem models play a crucial role in understanding and evaluating the combined
      impacts of rising atmospheric CO2 concentration and changing climate on
      terrestrial ecosystems. However, we are not aware of any studies where the
      capacity of models to simulate intra- and inter-annual variation in responses to
      elevated CO2 has been tested against long-term experimental data. Here we tested
      how well the ecosystem model APSIM/AgPasture was able to simulate the results
      from a free air carbon dioxide enrichment (FACE) experiment on grazed pasture. At
      this FACE site, during 11 years of CO2 enrichment, a wide range in annual plant
      production response to CO2 (-6 to +28%) was observed. As well as running the full
      model, which includes three plant CO2 response functions (plant photosynthesis,
      nitrogen (N) demand and stomatal conductance), we also tested the influence of
      these three functions on model predictions. Model/data comparisons showed that:
      (i) overall the model over-predicted the mean annual plant production response to
      CO2 (18.5% cf 13.1%) largely because years with small or negative responses to
      CO2 were not well simulated; (ii) in general seasonal and inter-annual variation
      in plant production responses to elevated CO2 were well represented by the model;
      (iii) the observed CO2 enhancement in overall mean legume content was well
      simulated but year-to-year variation in legume content was poorly captured by the
      model; (iv) the best fit of the model to the data required all three CO2 response
      functions to be invoked; (v) using actual legume content and reduced N fixation
      rate under elevated CO2 in the model provided the best fit to the experimental
      data. We conclude that in temperate grasslands the N dynamics (particularly the
      legume content and N fixation activity) play a critical role in pasture
      production responses to elevated CO2 , and are processes for model improvement. 

PMID- 23959971
TI  - Hydrostatic pressure and shear stress affect endothelin-1 and nitric oxide
      release by endothelial cells in bioreactors.
AB  - Abundant experimental evidence demonstrates that endothelial cells are sensitive
      to flow; however, the effect of fluid pressure or pressure gradients that are
      used to drive viscous flow is not well understood. There are two principal
      physical forces exerted on the blood vessel wall by the passage of intra-luminal
      blood: pressure and shear. To analyze the effects of pressure and shear
      independently, these two stresses were applied to cultured cells in two different
      types of bioreactors: a pressure-controlled bioreactor and a laminar flow
      bioreactor, in which controlled levels of pressure or shear stress, respectively,
      can be generated. Using these bioreactor systems, endothelin-1 (ET-1) and nitric
      oxide (NO) release from human umbilical vein endothelial cells were measured
      under various shear stress and pressure conditions. Compared to the controls, a
      decrease of ET-1 production by the cells cultured in both bioreactors was
      observed, whereas NO synthesis was up-regulated in cells under shear stress, but
      was not modulated by hydrostatic pressure. These results show that the two
      hemodynamic forces acting on blood vessels affect endothelial cell function in
      different ways, and that both should be considered when planning in vitro
      experiments in the presence of flow. Understanding the individual and synergic
      effects of the two forces could provide important insights into physiological and
      pathological processes involved in vascular remodeling and adaptation. 

PMID- 23959972
TI  - Reply: To PMID 23703931.

PMID- 23959973
TI  - Identification of a novel, recurrent MBTD1-CXorf67 fusion in low-grade
      endometrial stromal sarcoma.
AB  - Endometrial stromal sarcomas (ESSs) are a genetically heterogeneous group of rare
      uterine neoplasms that are commonly driven by recurrent gene rearrangements. In
      conventional low-grade ESS, JAZF1-SUZ12, PHF1-JAZF1, EPC1-PHF1 and MEAF6-PHF1,
      and recently described ZC3H7-BCOR chimeric fusions have been reported in > 50% of
      cases. Conversely, oncogenic t(10;17)(q22;p13) translocation yields YWHAE
      FAM22A/B chimeric proteins that are associated with histologically high-grade and
      clinically more aggressive ESS. Integrating whole-transcriptome paired-end RNA
      sequencing with fluorescence in situ hybridization (FISH) and banding
      cytogenetics, we identified MBTD1 (malignant brain tumor domain-containing 1) and
      CXorf67 (chromosome X open reading frame 67) as the genes involved in the novel
      reciprocal t(X;17)(p11.2;q21.33) translocation in two independent low-grade ESS
      of classical histology. The presence of the MBTD1-CXorf67 fusion transcript was
      validated in both cases using reverse-transcription polymerase chain reaction
      followed by Sanger sequencing. A specific FISH assay was developed to detect the
      novel t(X;17) translocation in formalin-fixed paraffin-embedded material, and
      resulted in identification of an additional low-grade ESS case positive for the
      MBTD1-CXorf67 fusion among 25 uterine stromal tumors [14 ESS and 11
      undifferentiated endometrial sarcomas (UESs)] that were negative for JAZF1 and
      YWHAE rearrangements. Gene expression profiles of seven ESS (including three with
      YWHAE and two with JAZF1 rearrangements) and four UES without specific
      chromosomal aberrations indicated clustering of tumors with MBTD1-CXorf67 fusion
      together with low-grade JAZF1-associated ESS. The chimeric MBTD1-CXorf67 fusion
      identifies yet another cytogenetically distinct subgroup of low-grade ESS and
      offers the opportunity to shed light on the functions of two poorly characterized
      genes. 

PMID- 23959974
TI  - Enhanced human bone marrow mesenchymal stem cell functions in novel 3D cartilage
      scaffolds with hydrogen treated multi-walled carbon nanotubes.
AB  - Cartilage tissue is a nanostructured tissue which is notoriously hard to
      regenerate due to its extremely poor inherent regenerative capacity and complex
      stratified architecture. Current treatment methods are highly invasive and may
      have many complications. Thus, the goal of this work is to use nanomaterials and
      nano/microfabrication methods to create novel biologically inspired tissue
      engineered cartilage scaffolds to facilitate human bone marrow mesenchymal stem
      cell (MSC) chondrogenesis. To this end we utilized electrospinning to design and
      fabricate a series of novel 3D biomimetic nanostructured scaffolds based on
      hydrogen (H2) treated multi-walled carbon nanotubes (MWCNTs) and biocompatible
      poly(L-lactic acid) (PLLA) polymers. Specifically, a series of electrospun
      fibrous PLLA scaffolds with controlled fiber dimension were fabricated in this
      study. In vitro MSC studies showed that stem cells prefer to attach in the
      scaffolds with smaller fiber diameter. More importantly, the MWCNT embedded
      scaffolds showed a drastic increase in mechanical strength and a compressive
      Young's modulus matching to natural cartilage. Furthermore, our MSC
      differentiation results demonstrated that incorporation of the H2 treated carbon
      nanotubes and poly-L-lysine coating can induce more chondrogenic differentiations
      of MSCs than controls. After two weeks of culture, PLLA scaffolds with H2 treated
      MWCNTs and poly-L-lysine can achieve the highest glycosaminoglycan synthesis,
      making them promising for further exploration for cartilage regeneration. 

PMID- 23959975
TI  - Expert-novice differences in mental models of viruses, vaccines, and the causes
      of infectious disease.
AB  - Humans are exposed to viruses everywhere they live, play, and work. Yet people's
      beliefs about viruses may be confused or inaccurate, potentially impairing their
      understanding of scientific information. This study used semi-structured
      interviews to examine people's beliefs about viruses, vaccines, and the causes of
      infectious disease. We compared people at different levels of science expertise:
      middle school students, teachers, and professional virologists. The virologists
      described more entities involved in microbiological processes, how these entities
      behaved, and why. Quantitative and qualitative analyses revealed distinctions in
      the cognitive organization of several concepts, including infection and
      vaccination. For example, some students and teachers described viral replication
      in terms of cell division, independent of a host. Interestingly, most students
      held a mental model for vaccination in which the vaccine directly attacks a virus
      that is present in the body. Our findings have immediate implications for how to
      communicate about infectious disease to young people.

PMID- 23959976
TI  - A powerful method for combining P-values in genomic studies.
AB  - After genetic regions have been identified in genomewide association studies
      (GWAS), investigators often follow up with more targeted investigations of
      specific regions. These investigations typically are based on single nucleotide
      polymorphisms (SNPs) with dense coverage of a region. Methods are thus needed to
      test the hypothesis of any association in given genetic regions. Several
      approaches for combining P-values obtained from testing individual SNP hypothesis
      tests are available. We recently proposed a sequential procedure for testing the
      global null hypothesis of no association in a region. When this global null
      hypothesis is rejected, this method provides a list of significant hypotheses and
      has weak control of the family-wise error rate. In this paper, we devise a
      permutation-based version of the test that accounts for correlations of tests
      based on SNPs in the same genetic region. Based on simulated data, the method has
      correct control of the type I error rate and higher or comparable power to other
      tests. 

PMID- 23959977
TI  - Immunostaining of germline stem cells and the niche in Drosophila ovaries.
AB  - Stem cells have the ability to switch between proliferative (self-renewal) and
      differentiation modes. The Drosophila germarium is a well-established in vivo
      model for the study of communication between stem cells and their niche. One
      commonly used technique for such study is immunostaining that allows examination
      of protein localization at a fixed time point. This chapter provides a detailed
      protocol for immunofluorescence staining of Drosophila ovaries. This protocol has
      been optimized to enable explicit visualization of the niche structure, as well
      as to maximize the degree of multiplexing for protein labeling and detection. 

PMID- 23959978
TI  - Genetic, immunofluorescence labeling, and in situ hybridization techniques in
      identification of stem cells in male and female germline niches.
AB  - Stem cells have an enormous capacity of self-renewal, as well as the ability to
      differentiate into specialized cell types. Proper control of these two properties
      of stem cells is crucial for animal development, growth control, and
      reproduction. Germline stem cells (GSCs) are a self-renewing population of germ
      cells, which generate haploid gametes (sperms or oocyte) that transmit genetic
      information from generation to generation. In Drosophila testis and ovary, GSCs
      are anchored around the niche cells. The cap cells cluster in females and hub
      cells in males act as a niche to control GSC behavior. With highly sophisticated
      genetic techniques in Drosophila, tremendous progress has been made in
      understanding the interactions between stem cells and niches at cellular and
      molecular levels. Here, we provide details of genetic, immunofluorescence
      labeling, and in situ hybridization techniques in identification and
      characterization of stem cells in Drosophila male and female germline niches. 

PMID- 23959979
TI  - Visualization of adult stem cells within their niches using the Drosophila
      germline as a model system.
AB  - The germaria of the fruit fly Drosophila melanogaster present an excellent model
      to study germline stem cell-niche interactions. Two to three adult stem cells are
      surrounded by a number of somatic cells that form the niche. Here we describe how
      Drosophilae germaria can be dissected and specifically immuno-stained to allow
      for identification and analysis of both the adult stem cells and their somatic
      niche cells. 

PMID- 23959980
TI  - Morphometric evaluation of the spermatogonial stem cell distribution and niche in
      vertebrates.
AB  - Morphometry is a classical quantitative method often used in biology to provide a
      data basis for functional interpretations/interactions of a particular organ or
      system. Herein we took advantage of this valuable approach to evaluate the
      spermatogonial stem cell niche using the horse testis and immunocytochemical
      localization of GFRA1 [glial cell line-derived neurotrophic factor receptor
      produced by Sertoli cells)] as an example. Using the NIH ImageJ free software, we
      describe in detail all the necessary steps to investigate this specific and
      crucial microenvironment. Based on several recently published papers from our
      research group, this approach has proved to be fast, simple, and adaptable to a
      wide range of species and has the potential to be easily reproducible in
      different laboratories. 

PMID- 23959981
TI  - In vitro construction of 2D and 3D simulations of the murine hematopoietic niche.
AB  - Hematopoietic stem cells (HSC) undergo multilineage differentiation or self
      renewal to maintain normal hematopoiesis and to sustain the size of the HSC pool
      throughout life. These processes are determined by a complex interplay of
      molecular signals between HSC and other cellular components such as osteoblasts
      (OB), stromal cells, endothelial cells, and a number of extracellular matrix
      (ECM) proteins. Through changes in its physical properties within the bone marrow
      (BM) microenvironment, collagen, which is one of the most critical ECM proteins,
      can modulate HSC function and maintenance of the competence of the hematopoietic
      niche (HN). At present, there is no consensus as to how different cellular
      elements of the niche collaborate and interact to promote HSC self-renewal or
      differentiation to maintain hematopoiesis. Deciphering these interactions and the
      impact of mechanical properties of the collagen microstructures within the HN has
      critical clinical implications in the areas of stem cell homing, engraftment, and
      maintenance of HSC function. In this chapter, we describe several of the in vitro
      methodologies for establishing and maintaining HSC in vitro including the
      isolation of OB, stromal cells, and hematopoietic progenitor cells, as well as
      the establishment of both two-dimensional (2D) and three-dimensional (3D)
      coculture systems. 

PMID- 23959982
TI  - Isolation of embryonic hematopoietic niche cells by flow cytometry and laser
      capture microdissection.
AB  - Hematopoietic stem cells (HSCs) can differentiate into several types of
      hematopoietic cells, such as erythrocytes, megakaryocytes, lymphocytes,
      neutrophils, or macrophages, and also undergo self-renewal to sustain
      hematopoiesis throughout an organism's lifetime. HSCs emerge and expand during
      mouse embryogenesis. HSC regulation is governed by two types of activity:
      intrinsic activity programmed primarily by cell autonomous gene expression, and
      extrinsic factors, which originate from the so-called niche cells surrounding
      HSCs. Previously, we reported that endothelial niche cells regulate HSC
      generation at aorta-gonad-mesonephros region and placenta, and that hepatoblastic
      niche cells regulate HSC differentiation in mouse embryonic liver. In the course
      of those studies, we employed immunohistochemistry, flow cytometry, and the laser
      capture microdissection system to assess embryonic regulation of the mouse
      hematopoietic niche. 

PMID- 23959983
TI  - Isolation and enrichment of Stro-1 immunoselected mesenchymal stem cells from
      adult human bone marrow.
AB  - The availability of mesenchymal stem cells (MSCs) or skeletal stem cells (SSCs)
      is vital to many of the tissue engineering strategies currently being developed
      for repairing bone and cartilage. One difficulty with using this cell population
      is that SSCs represent only a small fraction of the cells available from an
      individual patient's bone marrow sample, typically less than 1 in 10,000.
      Therefore, methods have been devised to enrich the proportion of MSCs obtained
      from a bone marrow sample using hybridoma cell lines to generate antibodies to
      cell surface antigens specific for MSCs. Stro-1 is the most widely targeted of
      these cell surface antigens. The protocol described overleaf is used to isolate
      and enrich the Stro-1 positive fraction of cells from a bone marrow aspirate to
      provide a sample enriched for MSCs for use in both in vitro and in vivo studies. 

PMID- 23959984
TI  - Primary marrow-derived stromal cells: isolation and manipulation.
AB  - Marrow stromal cells (MSCs) are relatively rare cells difficult to visualize in
      marrow biopsies or detect in aspirated marrow. Under specific conditions MSC can
      be expanded in vitro and the population can give rise to several mesenchymal
      lineages. "MSC" also refers to mesenchymal stem cells which implies that all
      cells in the population are multipotent. It is generally agreed that while there
      may be a few multipotent stem cells in an MSC population the majority are not
      stem cells. In either case MSCs do not produce hematopoietic cells. Although MSCs
      have been isolated and characterized from several tissues, bone marrow is their
      most common source for research and clinical use. Primary MSC populations can be
      derived from bone marrow mononuclear cells with relative ease, but it is
      important to recognize the cellular heterogeneity within a culture and how this
      may vary from donor to donor. In this chapter, we describe methodology to derive
      primary MSCs from bone marrow screens, an otherwise discarded by-product of bone
      marrow harvests used for clinical transplantation. We also describe some useful
      techniques to characterize and manipulate MSCs-both primary and immortalized cell
      lines. 

PMID- 23959985
TI  - Detection in vitro and quantitative estimation of artificial microterritories
      which promote osteogenic differentiation and maturation of stromal stem cells.
AB  - Extracellular matrix can regulate multipotent mesenchymal stromal cells (MMSC)
      differentiation, with potential applications for tissue engineering. A relief of
      mineralized bone takes essential effect on MMSC fate. Nevertheless, delicate
      structure and a hierarchy of niches for stromal stem cells and its quantitative
      parameters are not practically known. Here, we describe the protocol to define
      the basic approach providing a guiding for in vitro identification of
      quantitative features of artificial calcium phosphate niches which promotes
      osteogenic differentiation and maturation of stromal stem cell. 

PMID- 23959986
TI  - The prospective isolation of viable, high ploidy megakaryocytes from adult murine
      bone marrow by fluorescence activated cell sorting.
AB  - Mature megakaryocytes (MM) can be up to 65 MUM in diameter and due to their size,
      viable and pure MM populations have been difficult to isolate in large numbers.
      Here in, we report a fluorescence activated cell sorting (FACS) method by which
      viable and pure populations of 8 N, 16 N, 32 N, and 64 N MM can be isolated from
      murine bone marrow (BM). 

PMID- 23959987
TI  - Looking for the niche: substance delivery into the lateral ventricle of the
      brain: the osmotic minipump system.
AB  - The infusion of different substances into the left ventricle of the brain allows
      substances to reach the subventricular zone, one of the neural stem cell niches
      in the adult brain. Implantation of an osmotic minipump delivers proteins, virus
      and drugs directly into the lateral ventricle to act locally. Here we describe
      this method consisting on a cannula implanted into the lateral ventricle and
      linked to an osmotic minipump via catheter. The cannula is fixed over the brain
      and the minipump is placed subcutaneously. This system can be maintained from
      days up to several weeks and ensures constant and regular delivery of the desired
      biological product. 

PMID- 23959988
TI  - Unbiased stereological method to assess proliferation throughout the subependymal
      zone.
AB  - The subependymal zone (SEZ), frequently named as adult subventricular zone (SVZ),
      is a niche of adult neural stem and progenitor cells that lines a large extension
      of the lateral ventricles of the brain. The majority of the studies do not
      analyze the SEZ throughout its entire extension. Instead, studies of cell
      populations within the SEZ typically focus their analysis on a narrow space
      between specific bregma coordinates that provides a perspective of only a small
      portion of the SEZ. We have previously proposed a standard division for the SEZ
      at the anterior-posterior and dorsal-ventral axes based on external brain
      anatomical hallmarks (Falcao et al., PLoS One 7:e38647, 2012). Herein, we
      describe in detail the procedure and a stereological approach that can be used to
      obtain an unbiased estimation of the SEZ cell proliferation under physiological
      and pathological conditions. This approach takes into consideration clear SEZ
      anatomical divisions, both on the anterior-posterior and dorsal-ventral axes,
      which will standardize future studies on the SEZ. 

PMID- 23959990
TI  - Human and murine skeletal muscle reserve cells.
AB  - Study of stem cell phenotype and functions requires their proper isolation. Stem
      cells isolated from skeletal muscle are a useful tool to explore molecular
      pathways involved in the regulation of myogenesis. Among progenitor cells, a
      subset of cells, called reserve cells, has been identified, in vitro, in myogenic
      cell cultures. This subset of cells remains undifferentiated while the main
      population of progenitor cells commits to terminal myogenic differentiation. When
      replated, these reserve cells grow as new colonies of progenitors. At the time of
      differentiation, they reform both differentiated myotubes and undifferentiated
      reserve cells. Here, we present a protocol to obtain and further isolate reserve
      cells from both human and murine myogenic cell cultures, together with techniques
      to analyze their cell cycle status. 

PMID- 23959989
TI  - Cardiac stem cell niche, MMP9, and culture and differentiation of embryonic stem
      cells.
AB  - Embryonic stem cells (ESC) are totipotent, self-renewing, and clonogenic, having
      potential to differentiate into a wide variety of cell types. Due to regenerative
      capability, it has tremendous potential for treating myocardial infarction (death
      of myocardial tissue) and type 1 diabetes (death of pancreatic beta cells).
      Understanding the components regulating ESC differentiation is the key to unlock
      the regenerative potential of ESC-based therapies. Both the stiffness of
      extracellular matrix (ECM) and surrounding niche/microenvironment play pivotal
      roles in ESC differentiation. Matrix metalloproteinase-9 (MMP9) induces fibrosis
      that causes stiffness of the ECM and impairs differentiation of cardiac stem
      cells into cardiomyocytes. Here, we describe the method of ESC culture and
      differentiation, and the expression of MMP9 and its inhibitor, tissue inhibitor
      of metalloproteinase-4 (TIMP4) in differentiating ESC. 

PMID- 23959991
TI  - Modulation of the host skeletal muscle niche for donor satellite cell grafting.
AB  - Skeletal muscle tissue has a remarkable capability of regenerating in
      pathological conditions or after injury. The principal muscle stem cells,
      satellite cells, are responsible for this prompt and efficient process. Normally
      quiescent in their niches underneath the basal lamina of each muscle fiber,
      satellite cells become activated to repair or form new fibers. Ideally, healthy
      donor stem cells could be transplanted to regenerate the skeletal muscle tissue
      to repair a genetic defect. However, to be efficient, cell grafting requires
      modulation of the host muscle environment to allow homing of, and regeneration
      by, donor satellite cells. Here, we provide methods to modulate the host mouse
      muscle environment in order to destroy or preserve the muscle niche before
      transplanting donor satellite cells. We also describe methods to investigate
      donor-derived muscle regeneration and self-renewal. 

PMID- 23959992
TI  - Isolation of c-Kit+ human amniotic fluid stem cells from second trimester.
AB  - Amniotic fluid-derived stem (AFS) cells have been described as an appealing
      source of stem cells because of their (1) fetal, non-embryonic origin, (2) easy
      access during pregnancy overcoming the ethical issues related both to the use of
      human embryonic cells and to the postnatal tissue biopsy with donor site
      morbidity, and (3) their undemanding ability to be expanded. We and others have
      demonstrated the broad differentiation potential and here we describe the
      established protocol we developed to obtain c-Kit+ human AFS cells, starting from
      second trimester amniocentesis samples. 

PMID- 23959993
TI  - Hypoxia and visualization of the stem cell niche.
AB  - It is widely accepted that mammalian stem cells reside in a specialized cellular
      and a cellular microenvironment called the niche. The niche contrary to other
      tissues is characterized by a low partial Oxygen pressure (ppO2). This
      microenvironment protects stem cells from deleterious effects of O2 on proteins
      and DNA, through the production of reactive oxygen species (ROS). In addition
      there is now solid evidence that this physiological hypoxia helps stem cells
      maintaining their major characteristics: multipotency and ability to
      differentiate and migrate from the niche to specialized tissues in order to
      fulfill the needs of the organism. Immuno Histological techniques can stain stem
      cells in situ by specific Abs (such as against CD34 and CD45 for Hematopoietic
      Stem Cells HSC). However, a universal marker of hypoxia is Hypoxia-Inducible
      Factor-1, HIF-1, which is stabilized by low ppO2 and acts as a transcription
      factor to regulate a vast array of genes downstream. HIF-1, together with
      pimonidazole, a chemical compound interacting with proteins that are reduced in a
      hypoxic environment, are bona fide markers of the stem cell niche. 

PMID- 23959994
TI  - Detection and isolation of human disseminated tumor cells in the murine bone
      marrow stem cell niche.
AB  - The presence of disseminated tumor cells (DTCs) in the bone marrow is associated
      with poor prognosis of cancer patients. However, little is known about the
      biology of DTCs due to lack of relevant animal models. Here, we describe the
      methods for detecting and isolating human DTCs from the murine bone marrow niche
      by PCR using human Alu sequences and by fluorescence-activated cell sorting and
      immunohistochemistry using anti-HLA antibody. These strategies could be useful
      for exploring the biology of DTCs. 

PMID- 23959995
TI  - Identification and separation of normal hematopoietic stem cells and leukemia
      stem cells from patients with acute myeloid leukemia.
AB  - Mounting evidences indicate that leukemic cells in patients with acute myeloid
      leukemia (AML) are derived from leukemia stem cells (LSC). In analogy to normal
      hematopoietic stem cells (HSC), LSC remain mostly dormant and are hence resistant
      to conventional chemotherapy. Residual, physiological HSC exist alongside with
      LSC, with heterogeneous dominance of LSC over HSC in individual patients. We have
      devised a flow cytometric method for the identification and separation of these
      two stem cell populations based on surface antigen markers such as CD34, CD38,
      lineage aberrant markers, and aldehyde dehydrogenase (ALDH) enzyme activity. 

PMID- 23959996
TI  - Serial orthotopic transplantation of epithelial tumors in single-cell suspension.
AB  - Orthotopic transplantation of tumor tissue into recipient mice has long been
      established to study the role of the microenvironment in tumorigenesis and
      metastasis. Many of these transplantation assays involve the surgical
      implantation of an undissociated piece of tumor tissue. However, dissociation of
      tumor tissue into a single cell suspension prior to orthotopic transplantation
      enables the injection of fewer cell numbers, the selection of tumor-initiating
      populations by specific purification using antibody staining and fluorescence
      activated cell sorting, and the analysis of tumor-forming efficiency.In this
      chapter, we provide a method to perform serial transplantation of tumor cells
      into their niche of origin. Visualization of the location of transplanted tumor
      cells is essential to confirm the success of the transplant as well as the
      viability of transplanted cells. We also describe an optimized immunofluorescence
      protocol to visualize tumor cells shortly after transplantation. This serial
      transplantation protocol allows for an experimental tumorigenesis assay to more
      closely mimic spontaneous tumor formation and is applicable to many
      microenvironments. 

PMID- 23959997
TI  - Isolation and propagation of colon cancer stem cells.
AB  - The design of tissue culture conditions that faithfully reproduce the
      characteristics of cells in their native environment remains one of the main
      challenges of cancer stem cell (CSC) biology. Here we describe a detailed
      methodology for the isolation and expansion of both human colon CSCs and mouse
      intestinal adenoma together with a brief differentiation and coculture method
      that proved to be valuable to study the concept of CSCs plasticity. 

PMID- 23959998
TI  - Prevalence of hepatitis C virus genotypes in risk groups in the Republic of
      Macedonia: a 5 years survey.
AB  - The prevalence of hepatitis C virus (HCV) genotypes depends on geographical
      location. HCV genotyping is important for epidemiological investigations and
      treatment management. The aim of this study was to determine the HCV genotype
      prevalence in the most prominent risk groups in the Republic of Macedonia in the
      last 5 years and to evaluate its association with patient's age, gender, and mode
      of transmission. A total of 1,167 HCV positive patients, divided into three risk
      groups (intravenous drug use, chronic hemodialysis, and other risk factor), were
      genotyped using an in-house ASO hybridization method with genotype-specific
      oligonucleotide probes. The genotypes 1, 2, and 3 were present with 52.2%, 0.6%,
      and 47.0%, respectively. Genotype 1 was most prevalent in hemodialysis (89.0%)
      and other risk factor group (53.8%). It was found associated independently with
      hemodialysis, age >40 and female gender. Genotype 3 predominated in intravenous
      drug users (64.0%) and was associated significantly also with age <=40 and male
      gender. Multivariable logistic regression analysis pointed out hemodialysis (P <
      0.0001, Exp (B) = 12.0) as a positive predictor factor for genotype 1 and age
      <=40 (P = 0.021, Exp (B) = 1.8) and intravenous drug use (P < 0.0001, Exp (B) =
      8.4) as a positive predictor factors for genotype 3. In conclusion, the main
      transmission route of HCV infection in the Republic of Macedonia is intravenous
      drug use, followed by hemodialysis. HCV genotypes 1 and 3 dominate in these two
      most prominent risk groups in the Republic of Macedonia.

PMID- 23959999
TI  - Orphan viruses, orphan diseases: still the raw material for virus discovery.

PMID- 23960000
TI  - Three-dimensional computer graphics-based ankle morphometry with computerized
      tomography for total ankle replacement design and positioning.
AB  - Morphometry of the bones of the ankle joint is important for the design of joint
      replacements and their surgical implantations. However, very little three
      dimensional (3D) data are available and not a single study has addressed the
      Chinese population. Fifty-eight fresh frozen Chinese cadaveric ankle specimens,
      26 females, and 32 males, were CT-scanned in the neutral position and their 3D
      computer graphics-based models were reconstructed. The 3D morphology of the
      distal tibia/fibula segment and the full talus was analyzed by measuring 31
      parameters, defining the relevant dimensions, areas, and volumes from the models.
      The measurements were compared statistically between sexes and with previously
      reported data from Caucasian subjects. The results showed that, within a general
      similarity of ankle morphology between the current Chinese and previous Caucasian
      subjects groups, there were significant differences in 9 out of the 31 parameters
      analyzed. From a quantitative comparison with available prostheses designed for
      the Caucasian population, few of these designs have both tibial and talar
      components suitable in dimension for the Chinese population. The current data
      will be helpful for the sizing, design, and surgical positioning of ankle
      replacements and for surgical instruments, especially for the Chinese population.

PMID- 23960001
TI  - Effects of drought and pluvial periods on fish and zooplankton communities in
      prairie lakes: systematic and asystematic responses.
AB  - The anticipated impacts of climate change on aquatic biota are difficult to
      evaluate because of potentially contrasting effects of temperature and hydrology
      on lake ecosystems, particularly those closed-basin lakes within semiarid
      regions. To address this shortfall, we quantified decade-scale changes in
      chemical and biological properties of 20 endorheic lakes in central North America
      in response to a pronounced transition from a drought to a pluvial period during
      the early 21st century. Lakes exhibited marked temporal changes in chemical
      characteristics and formed two discrete clusters corresponding to periods of
      substantially different effective moisture (as Palmer Drought Severity Index,
      PDSI). Discriminant function analysis (DFA) explained 90% of variability in fish
      assemblage composition and showed that fish communities were predicted best by
      environmental conditions during the arid interval (PDSI <-2). DFA also predicted
      that lakes could support more fish species during pluvial periods, but their
      occurrences may be limited by periodic stress due to recurrent droughts and
      physical barriers to colonization. Zooplankton taxonomic assemblages in fishless
      lakes were resilient to short-term changes in meteorological conditions, and did
      not vary between drought and deluge periods. Conversely, zooplankton taxa in fish
      populated lakes decreased substantially in biomass during the wet interval,
      likely due to increased zooplanktivory by fish. The powerful effects of such
      climatic variability on hydrology and the strong subsequent links to water
      chemistry and biota indicate that future changes in global climate could result
      in significant restructuring of aquatic communities. Together these findings
      suggest that semiarid lakes undergoing temporary climate shifts provide a useful
      model system for anticipating the effects of global climate change on lake food
      webs. 

PMID- 23960002
TI  - Transarterial chemoembolization of unresectable systemic chemotherapy-refractory
      liver metastases from colorectal cancer: long-term results over a 10-year period.
AB  - The aims of the study were to evaluate therapeutic efficacy and to determine the
      prognostic factors for treatment success in patients with liver metastases from
      colorectal cancer (CRC) treated with transarterial chemoembolization (TACE). A
      total of 564 patients (mean age, 60.3 years) with liver metastases of CRC were
      repeatedly treated with TACE. In total, 3,384 TACE procedures were performed
      (mean, six sessions per patient). The local chemotherapy protocol consisted of
      mitomycin C alone (43.1%), mitomycin C with gemcitabine (27.1%), mitomycin C with
      irinotecan (15.6%) or mitomycin C with irinotecan and cisplatin (15.6%).
      Embolization was performed with lipiodol and starch microspheres. Tumor response
      was evaluated using magnetic resonance imaging or computed tomography. The change
      in tumor size was calculated and the response was evaluated according to the
      RECIST-Criteria. Survival rates were calculated according to the Kaplan-Meier
      method. Prognostic factors for patient's survival were evaluated using log-rank
      test. Evaluation of local tumor control showed partial response in 16.7%, stable
      disease in 48.2% and progressive disease in 16.7%. The 1-year survival rate after
      chemoembolization was 62%, the 2-year survival rate was 28% and the 3-year
      survival rate was 7%. Median survival from the start of chemoembolization
      treatment was 14.3 months. The indication (p = 0.001) and initial tumor response
      (p = 0.015) were statistically significant factors for patient's survival. TACE
      is a minimally invasive therapy option for controlling local metastases and
      improving survival time in patients with hepatic metastases from CRC. TN stage,
      extrahepatic metastases, number of lesions, tumor location within the liver and
      choice of chemotherapy protocol of TACE are none significant factors for
      patient's survival. 

PMID- 23960003
TI  - Did postoperative peg-interferon plus ribavirin really reduce recurrence of
      hepatitis C virus-related hepatocellular carcinoma?

PMID- 23960004
TI  - Efficient recovery of recombinant proteins from cereal endosperm is affected by
      interaction with endogenous storage proteins.
AB  - Cereal seeds are versatile platforms for the production of recombinant proteins
      because they provide a stable environment for protein accumulation. Endogenous
      seed storage proteins, however, include several prolamin-type polypeptides that
      aggregate and crosslink via intermolecular disulfide bridges, which could
      potentially interact with multimeric recombinant proteins such as antibodies,
      which assemble in the same manner. We investigated this possibility by
      sequentially extracting a human antibody expressed in maize endosperm, followed
      by precipitation in vitro with zein. We provide evidence that a significant
      proportion of the antibody pool interacts with zein and therefore cannot be
      extracted using non-reducing buffers. Immunolocalization experiments demonstrated
      that antibodies targeted for secretion were instead retained within zein bodies
      because of such covalent interactions. Our findings suggest that the production
      of soluble recombinant antibodies in maize could be enhanced by eliminating or
      minimizing interactions with endogenous storage proteins. 

PMID- 23960005
TI  - Activation of an intense near band edge emission from ZnTe/ZnMgTe core/shell
      nanowires grown on silicon.
AB  - The absence of luminescence in the near band edge energy region of Te-anion based
      semiconductor nanowires grown by gold catalyst assisted molecular beam epitaxy
      has strongly limited their applications in the field of photonics. In this paper,
      an enhancement of the near band edge emission intensity from ZnTe/ZnMgTe
      core/shell nanowires grown on Si substrates is reported. A special role of the
      use of Si substrates instead of GaAs substrates is emphasized, which results in
      an increase of the near band edge emission intensity by at least one order of
      magnitude accompanied by a simultaneous reduction of the defect related
      luminescence. A possible explanation of this effect relies on the presence of Ga
      related deep level defects in structures grown on GaAs substrates, which are
      absent when Si substrates are used. Monochromatic mapping of the
      cathodoluminescence clearly confirms that the observed emission originates,
      indeed, from the ZnTe/ZnMgTe core/shell nanowires, whereas individual objects are
      studied by means of microphotoluminescence. 

PMID- 23960007
TI  - Body MRI artifacts in clinical practice: a physicist's and radiologist's
      perspective.
AB  - The high information content of MRI exams brings with it unintended effects,
      which we call artifacts. The purpose of this review is to promote understanding
      of these artifacts, so they can be prevented or properly interpreted to optimize
      diagnostic effectiveness. We begin by addressing static magnetic field
      uniformity, which is essential for many techniques, such as fat saturation. Eddy
      currents, resulting from imperfect gradient pulses, are especially problematic
      for new techniques that depend on high performance gradient switching.
      Nonuniformity of the transmit radiofrequency system constitutes another source of
      artifacts, which are increasingly important as magnetic field strength increases.
      Defects in the receive portion of the radiofrequency system have become a more
      complex source of problems as the number of radiofrequency coils, and the
      sophistication of the analysis of their received signals, has increased. Unwanted
      signals and noise spikes have many causes, often manifesting as zipper or banding
      artifacts. These image alterations become particularly severe and complex when
      they are combined with aliasing effects. Aliasing is one of several phenomena
      addressed in our final section, on artifacts that derive from encoding the MR
      signals to produce images, also including those related to parallel imaging,
      chemical shift, motion, and image subtraction.

PMID- 23960011
TI  - Torque teno virus (TTV) in multiple sclerosis patients with different patterns of
      disease.
AB  - Torque teno virus (TTV) is highly prevalent in the general population worldwide.
      The relationship that TTV establishes with the central nervous system (CNS) of
      infected hosts is not clear but it is suspected that TTV infection of the CNS
      lead to increased local expression of inflammatory mediators that may play a role
      in the pathogenesis of multiple sclerosis (MS). The prevalence and load of TTV in
      serum and cerebrospinal fluid (CSF) of 207 MS patients and 93 age- and sex
      matched healthy controls by qPCR designed on the untranslated region were
      analyzed. TTV DNA was not detected in CSF, TTV prevalence in serum was similar in
      MS patients (76.8%) compared to healthy controls (76.3%). Sub analyses performed
      in MS patients stratified on the basis of clinical phenotypes indicated that TTV
      viremia was significantly lower in individuals with relapsing remitting compared
      to chronic progressive disease. Notably, viremia was increased in primary
      progressive, compared to secondary progressive MS patients, and in relapsing
      remitting MS patients during quiescent compared to relapsing phases of disease.
      Since TTV interacts with toll-like receptor (TLR) stimulating the production of
      inflammatory cytokines, TLR9 expression were examined, showing that it was
      augmented on monocytes of chronic progressive MS patients, in whom higher TTV
      viremia was present, but this did not correlate with a distinct pattern of
      cytokine production. Overall these findings suggest that, although TTV infects
      the same proportion of MS patients and healthy controls, the levels of
      replication of the virus differ among patients, being correlated with the
      clinical phenotype of disease.

PMID- 23960006
TI  - Whole body MRI: improved lesion detection and characterization with diffusion
      weighted techniques.
AB  - Diffusion-weighted imaging (DWI) is an established functional imaging technique
      that interrogates the delicate balance of water movement at the cellular level.
      Technological advances enable this technique to be applied to whole-body MRI.
      Theory, b-value selection, common artifacts and target to background for
      optimized viewing will be reviewed for applications in the neck, chest, abdomen,
      and pelvis. Whole-body imaging with DWI allows novel applications of MRI to aid
      in evaluation of conditions such as multiple myeloma, lymphoma, and skeletal
      metastases, while the quantitative nature of this technique permits evaluation of
      response to therapy. Persisting signal at high b-values from restricted
      hypercellular tissue and viscous fluid also permits applications of DWI beyond
      oncologic imaging. DWI, when used in conjunction with routine imaging, can assist
      in detecting hemorrhagic degradation products, infection/abscess, and
      inflammation in colitis, while aiding with discrimination of free fluid and
      empyema, while limiting the need for intravenous contrast. DWI in conjunction
      with routine anatomic images provides a platform to improve lesion detection and
      characterization with findings rivaling other combined anatomic and functional
      imaging techniques, with the added benefit of no ionizing radiation.

PMID- 23960012
TI  - Targeting intracellular pathogenic bacteria with unnatural proline-rich peptides:
      coupling antibacterial activity with macrophage penetration.

PMID- 23960014
TI  - Phosphatidylinositol-3-kinase pathway aberrations in gastric and colorectal
      cancer: meta-analysis, co-occurrence and ethnic variation.
AB  - Inhibition of the phosphatidylinositol-3-kinase (PI3K) signaling pathway is a
      cancer treatment strategy that has entered into clinical trials. We performed a
      meta-analysis on the frequency of prominent genetic (PIK3CA mutation, PIK3CA
      amplification and PTEN deletion) and protein expression (high PI3K, PTEN loss and
      high pAkt) aberrations in the PI3K pathway in gastric cancer (GC) and colorectal
      cancer (CRC). We also performed laboratory analysis to investigate the co
      occurrence of these aberrations. The meta-analysis indicated that East Asian and
      Caucasian GC patients differ significantly for the frequencies of PIK3CA Exon 9
      and 20 mutations (7% vs. 15%, respectively), PTEN deletion (21% vs. 4%) and PTEN
      loss (47% vs. 78%), while CRC patients differed for PTEN loss (57% vs. 26%). High
      study heterogeneity (I(2) > 80) was observed for all aberrations except PIK3CA
      mutations. Laboratory analysis of tumors from East Asian patients revealed
      significant differences between GC (n = 79) and CRC (n = 116) for the frequencies
      of PIK3CA amplification (46% vs. 4%) and PTEN loss (54% vs. 78%). The incidence
      of GC cases with 0, 1, 2 and 3 concurrent aberrations was 14%, 52%, 27% and 8%,
      respectively, while for CRC it was 10%, 60%, 25% and 4%, respectively. Our study
      consolidates knowledge on the frequency, co-occurrence and clinical relevance of
      PI3K pathway aberrations in GC and CRC. Up to 86% of GC and 90% of CRC have at
      least one aberration in the PI3K pathway, and there are significant differences
      in the frequencies of these aberrations according to cancer type and ethnicity.

PMID- 23960015
TI  - The role of the Saccharomyces cerevisiae lipoate protein ligase homologue, Lip3,
      in lipoic acid synthesis.
AB  - The covalent attachment of lipoate to the lipoyl domains (LDs) of the central
      metabolism enzymes pyruvate dehydrogenase (PDH) and oxoglutarate dehydrogenase
      (OGDH) is essential for their activation and thus for respiratory growth in
      Saccharomyces cerevisiae. A third lipoate-dependent enzyme system, the glycine
      cleavage system (GCV), is required for utilization of glycine as a nitrogen
      source. Lipoate is synthesized by extraction of its precursor, octanoyl-acyl
      carrier protein (ACP), from the pool of fatty acid biosynthetic intermediates.
      Alternatively, lipoate is salvaged from previously modified proteins or from
      growth medium by lipoate protein ligases (Lpls). The first Lpl to be
      characterized, LplA of Escherichia coli, catalyses two partial reactions:
      activation of the acyl chain by formation of acyl-AMP, followed by transfer of
      the acyl chain to lipoyl domains (LDs). There is a surprising diversity within
      the Lpl family of enzymes, several of which catalyse reactions other than
      ligation reactions. For example, the Bacillus subtilis Lpl homologue LipM is an
      octanoyltransferase that transfers the octanoyl moiety from octanoyl-ACP to GCV.
      Another B. subtilis Lpl homologue, LipL, transfers octanoate from octanoyl-GCV to
      other LDs in an amido-transfer reaction. Study of eukaryotic Lpls has lagged
      behind studies of the bacterial enzymes. We report that the Lip3 Lpl homologue of
      the yeast S. cerevisiae has octanoyl-CoA-protein transferase activity, and
      discuss implications of this activity on the physiological role of Lip3 in
      lipoate synthesis.

PMID- 23960016
TI  - Synthesis, G-quadruplex stabilisation, docking studies, and effect on cancer
      cells of indolo[3,2-b]quinolines with one, two, or three basic side chains.
AB  - G-quadruplex (G4) DNA structures in telomeres and oncogenic promoter regions are
      potential targets for cancer therapy, and G4 ligands have been shown to modulate
      telomerase activity and oncogene transcription. Herein we report the synthesis
      and G4 thermal stabilisation effects, determined by FRET melting assays, of 20
      indolo[3,2-b]quinolines mono-, di-, and trisubstituted with basic side chains.
      Molecular modelling studies were also performed in an attempt to rationalise the
      ligands' binding poses with G4. Overall, the results suggest that ligand binding
      and G4 DNA thermal stabilisation increase with an N5-methyl or a 7-carboxylate
      group and propylamine side chains, whereas selectivity between G4 and duplex DNA
      appears to be modulated by the number and relative position of basic side chains.
      From all the indoloquinoline derivatives studied, the novel trisubstituted
      compounds 3 d and 4 d, bearing a 7-(aminoalkyl)carboxylate side chain, stand out
      as the most promising compounds; they show high G4 thermal stabilisation (DeltaTm
      values between 17 and 8  degrees C) with an inter-G4 DeltaTm trend of
      Hsp90A>KRas21R~F21T>c-Kit2, 10-fold selectivity for G4 over duplex DNA, and 100
      fold selectivity for the HCT116 cancer cell line (IC50 and IC90: <10 MUM) over
      primary rat hepatocytes. Compounds 3 d and 4 d also decreased protein expression
      levels of Hsp90 and KRas in HCT116 cancer cells. 

PMID- 23960017
TI  - Human CD14+ CTLA-4+ regulatory dendritic cells suppress T-cell response by
      cytotoxic T-lymphocyte antigen-4-dependent IL-10 and indoleamine-2,3-dioxygenase
      production in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide
      with limited therapeutic options. HCC-induced immunosuppression often leads to
      ineffectiveness of immuno-promoting therapies. Currently, suppressing the
      suppressors has become the potential strategy for cancer immunotherapy. So,
      figuring out the immunosuppressive mechanisms induced and employed by HCC will be
      helpful to the design and application of HCC immunotherapy. Here, we identified
      one new subset of human CD14(+) CTLA-4(+) regulatory dendritic cells (CD14(+)
      DCs) in HCC patients, representing ~13% of peripheral blood mononuclear cells.
      CD14(+) DCs significantly suppress T-cell response in vitro through interleukin
      (IL)-10 and indoleamine-2,3-dioxygenase (IDO). Unexpectedly, CD14(+) DCs
      expressed high levels of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed
      death-1, and CTLA-4 was found to be essential to IL-10 and IDO production. So, we
      identified a novel human tumor-induced regulatory DC subset, which suppresses
      antitumor immune response through CTLA-4-dependent IL-10 and IDO production, thus
      indicating the important role of nonregulatory T-cell-derived CTLA-4 in tumor
      immune escape or immunosuppression. CONCLUSIONS: These data outline one mechanism
      for HCC to induce systemic immunosuppression by expanding CD14(+) DCs, which may
      contribute to HCC progression. This adds new insight to the mechanism for HCC
      induced immunosuppression and may also provide a previously unrecognized target
      of immunotherapy for HCC.

PMID- 23960018
TI  - Cardiac arrest during adult liver transplantation: a single institution's
      experience with 1238 deceased donor transplants.
AB  - Liver transplantation (LT) is one of the highest risk noncardiac surgeries. We
      reviewed the incidence, etiologies, and outcomes of intraoperative cardiac arrest
      (ICA) during LT. Adult cadaveric LT recipients from January 1, 2001 through
      December 31, 2009 were reviewed. ICA was defined as an event requiring either
      closed chest compression or open cardiac massage. Cardiac arrest patients who
      recovered with only pharmacological interventions were excluded. Data included
      etiologies and outcomes of ICA, intraoperative deaths (IDs) and hospital deaths
      (HDs), and potential ICA risk factors. ICA occurred in 68 of 1238 LT recipients
      (5.5%). It occurred most frequently during the neohepatic phase (60 cases or
      90%), and 39 of these cases (65.0%) experienced ICA within 5 minutes after graft
      reperfusion. The causes of ICA included postreperfusion syndrome (PRS; 26 cases
      or 38.2%) and pulmonary thromboembolism (PTE; 24 cases or 35.3%). A higher Model
      for End-Stage Liver Disease (MELD) score was found to be the most significant
      risk factor for ICA. The ID rate after ICA was 29.4% (20 cases), and the HD rate
      was 50.0% (34 cases). The 30-day patient survival rate after ICA was 55.9%, and
      the 1-year survival rate was 45.6%: these rates were significantly lower (P <
      0.001) than those for non-ICA patients (97.4% and 85.1%, respectively). In
      conclusion, the incidence of ICA in adult cadaveric LT was 5.5% with an
      intraoperative mortality rate of 29.4%. ICA most frequently occurred within 5
      minutes after reperfusion and resulted mainly from PRS and PTE. A higher MELD
      score was identified as a risk factor.

PMID- 23960019
TI  - Intramolecular OH...FC hydrogen bonding in fluorinated carbohydrates: CHF is a
      better hydrogen bond acceptor than CF2.
AB  - An intramolecular bifurcated H-bond from the axial HO-2 group to the axial F-4
      atom and to the O5 atom of alpha-D-hexopyranosides in apolar solvents is
      evidenced in (1)H NMR spectra. The H-accepting properties of the F atom are
      modulated by the orientation of the O-substituent at the C3 atom and by an
      additional F atom at the C4 atom.

PMID- 23960020
TI  - Herpesvirus detection and cytokine levels (IL-10, IL-6, and IFN-gamma) in ocular
      fluid from Tunisian immunocompetent patients with uveitis.
AB  - Human herpesviruses (HHVs) are involved in the pathogenesis of different types of
      uveitis. Cytokine response plays an important role in virus-induced
      immunopathology. This study aimed to investigate the incidence of HHVs in aqueous
      humor samples of immunocompetent patients with suspected viral uveitis and
      cytokine (IL-10, IL-6, and IFN-gamma) expression profiling. Forty-seven aqueous
      humor samples were collected from immunocompetent patients with viral uveitis.
      Samples were assayed for HHV-1 to HHV-8 by in-house real-time polymerase chain
      reactions. IL-6, IL-10, and IFN-gamma were quantified with a cytometric bead
      array. Relations between viral detection, cytokine profiles, and clinical data
      were studied. At least one viral genome was detected in 21 aqueous humor samples
      analyzed. Varicella-zoster virus (VZV) was detected in 14 of the positive
      samples, cytomegalovirus (CMV) in 8, HSV-1 in 1, Epstein-Barr virus (EBV) in 4,
      and HHV-6 in 2. More than one viral genome was detected in seven aqueous humor
      samples. Aqueous humor samples positive for HHV-DNA contained significant levels
      of IL-6, IL-10, and IFN-gamma, compared to HHV-DNA negative samples. High levels
      of IL-6 were detected in patients with CMV-DNA in their aqueous humor samples.
      Significantly higher levels of IL-10 and IFN-gamma were found in positive samples
      for VZV, EBV, and HHV-6 DNA than in negative aqueous humor ones. VZV was the
      principal etiologic agent of uveitis in this Tunisian series, with CMV the second
      most common agent. Knowledge of immunoregulatory interactions and dynamic changes
      in viral uveitis may be a key to understand the pathogenesis leading to more
      effective treatments.

PMID- 23960023
TI  - Carbodicarbenes, carbon(0) derivatives, can dimerize.

PMID- 23960024
TI  - Acute kidney injury in statin initiators.
AB  - PURPOSE: Statins are widely used for preventing cardiovascular disease, yet
      recent reports suggest an increased risk of acute kidney injury (AKI). We
      estimated the one-year risk of AKI associated with statin initiation and
      determined the comparative safety of individual statin formulations. METHODS: We
      performed a cohort study in insurance billing data from commercial and Medicare
      insurance plans in the United States for the years 2000-2010. We identified
      statin initiators and non-users with histories of medication use and healthcare
      utilization. AKI diagnosis codes were identified in the one year following the
      index date. We estimated hazard ratios (HR) and 95% confidence intervals (CI)
      with adjusted and propensity score (PS)-matched Cox-proportional hazards models.
      Models were run separately in insurance groups and adjusted for cardiovascular
      and renal risk factors, markers of healthcare utilization, and other medication
      use. RESULTS: We identified 3,905,155 statin initiators and 2,817,621 eligible
      non-users. The adjusted HR of AKI in statin initiators compared to non-users was:
      commercial, HR = 1.04 (95% CI: 0.99, 1.09); Medicare, HR = 0.72 (95% CI: 0.70,
      0.75). PS-matching yielded: commercial, HR = 0.82 (95% CI: 0.78, 0.87); Medicare,
      HR = 0.66 (95% CI: 0.63, 0.69). As individual formulations, higher-potency
      simvastatin was associated with an increased risk of AKI over lower-potency
      simvastatin in adjusted models: commercial, HR = 1.42 (95% CI: 1.28, 1.58);
      Medicare, HR = 1.24 (95% CI: 1.15, 1.35). CONCLUSIONS: As a class, statin
      initiation was not associated with an increase in AKI. However, higher-potency
      simvastatin did exhibit an increased AKI risk.

PMID- 23960026
TI  - Muscle mass predicts outcomes following liver transplantation.
AB  - For patients with end-stage liver disease, commonly used indices of nutritional
      status (ie, body weight and body mass index) are often inflated because of fluid
      overload (ie, ascites and peripheral edema), and this results in an
      underdiagnosis of malnutrition. Because muscle is the largest protein reservoir
      in the body, an estimate of the muscle mass may be a more reliable and valid
      estimate of nutritional status. Therefore, we used pretransplant computed
      tomography data for 338 liver transplantation (LT) candidates to identify muscle
      and fat mass on the basis of a specific abdominal transverse section commonly
      used in body composition analyses, and we investigated the contribution of this
      measure to specific post-LT outcomes. We found that the majority of our patients
      (68%) could be defined as cachectic. For men, muscle mass predicted many
      important posttransplant outcomes, including intensive care unit (ICU) stay,
      total length of stay (LOS), and days of intubation. Muscle mass was a significant
      predictor of survival and also predicted disposition to home versus another
      facility. For women, muscle mass predicted ICU stay, total LOS, and days of
      intubation, but the effect was modest. Muscle mass did not predict survival or
      disposition for women. In conclusion, because pretransplant muscle mass is
      associated with many important postoperative outcomes, we discuss these findings
      in the context of possible pretransplant interventions for either improving or
      sustaining muscle mass before surgery.

PMID- 23960027
TI  - Initial viral load in cases of single human papillomavirus 16 or 52 persistent
      infection is associated with progression of later cytopathological findings in
      the uterine cervix.
AB  - The aim of this study was to investigate the relationship between viral load in
      single human papillomavirus (HPV) 16 or 52 persistent infection and the
      progression of later cytopathological findings in the uterine cervix. Cervical
      cytology and HPV genotyping tests were repeated within 3-6 months in 305 women
      with oncogenic HPV. Twenty-four cases of single HPV 52 persistent infection and
      24 cases of single HPV 16 persistent infection were identified. Cases with later
      cytopathological findings showing progression were defined as the progression
      group, while those with no change or regression were the non-progression group.
      Relative HPV DNA loads were determined by quantitative real-time polymerase chain
      reaction and expressed relative to human albumin (ALB) DNA. Differences between
      the two groups were evaluated. The median relative HPV 52 DNA load was 2.211 in
      the progression group and 0.022 in the non-progression group (Mann-Whitney U
      test, P = 0.003). The median relative HPV 16 DNA load was 4.206 in the
      progression group and 0.103 in the non-progression group (P = 0.001). HPV 52 and
      16 DNA loads assessed by quantitative real-time methods may be useful short-term
      markers for identifying women at high risk for progression of cervical
      cytological pathology.

PMID- 23960028
TI  - Reliable and uniform thin-film transistor arrays based on inkjet-printed polymer
      semiconductors for full color reflective displays.
AB  - Stable uniform performance inkjet-printed polymer transistor arrays, which allow
      demonstration of flexible full-color displays, were achieved by new ambient
      processable conjugated copolymer semiconductor, and OTFT devices incorporating
      this material showed high mobility values>1.0 cm2 V(-1) s(-1). Bias-stress
      stability of the devices was improved with a channel-passivation layer, which
      suppresses the density of trap states at the channel interface.

PMID- 23960025
TI  - Bioorthogonal approach to identify unsuspected drug targets in live cells.
AB  - A proteomics method to pull down secondary drug targets from live cells is
      described. The drug of interest is modified with trans-cyclooctene (TCO) and
      incubated with live cells. Upon cell lysis, the modified drug bound to the
      protein is pulled down using magnetic beads decorated with a cleavable tetrazine
      modified linker. Samples are then run on an SDS-PAGE gel and isolated bands are
      submitted for mass spectrometry analysis to identify drug targets.

PMID- 23960029
TI  - Metformin therapy and kidney disease: a review of guidelines and proposals for
      metformin withdrawal around the world.
AB  - OBJECTIVE: We compared and contrasted guidelines on metformin treatment in
      patients with chronic kidney disease (CKD) around the world, with the aim of
      helping physicians to refine their analysis of the available evidence before
      deciding whether to continue or withdraw this drug. METHODS: We performed a
      systematic research for metformin contraindications in: (i) official documents
      from the world's 20 most populated countries and the 20 most scientifically
      productive countries in the field of diabetology and (ii) publications referenced
      in electronic databases from 1990 onwards. RESULTS: We identified three
      international guidelines, 31 national guidelines, and 20 proposals in the
      scientific literature. The criteria for metformin withdrawal were (i) mainly
      qualitative in the most populated countries; (ii) mainly quantitative in the most
      scientifically productive countries (with, in all cases, a suggested threshold
      for withdrawing metformin); and (iii) quantitative in all, but one of the
      literature proposals, with a threshold for withdrawal in most cases (n = 17)
      and/or adjustment of the metformin dose as a function of renal status (n = 8).
      There was a good degree of consensus on serum creatinine thresholds; whereas
      guidelines based on estimated glomerular filtration rate thresholds varied from
      60 mL/minute/1.73 m(2) up to stage 5 CKD. Only one of the proposals has been
      tested in a prospective study. CONCLUSIONS: In general, proposals for continuing
      or stopping metformin therapy in CKD involve a threshold (whether based on serum
      creatinine or estimated glomerular filtration rate) rather than the dose
      adjustment as a function of renal status (in stable patients) performed for other
      drugs excreted by the kidney.

PMID- 23960030
TI  - Versatile synthesis of benzothiophenes and benzoselenophenes by rapid assembly of
      arylzinc reagents, alkynes, and elemental chalcogens.
AB  - Rapidly aSSembled: The combination of cobalt-catalyzed migratory arylzincation
      and copper-mediated/catalyzed chalcogenative cyclization allows the construction
      of benzothiophenes and benzoselenophenes from arylzinc reagents, alkynes, and
      elemental chalcogens. Benzothiophenes and benzoselenophenes diversely
      functionalized at the benzene ring moiety can be prepared, which are not readily
      accessible by conventional methods. 

PMID- 23960031
TI  - Long-term quality of life for transplant recipients.

PMID- 23960032
TI  - Transesophageal echocardiography imaging of the total artificial heart.

PMID- 23960034
TI  - Thomas Linwood Bennett, MD: one of New York City's first prominent physician
      anesthetists.
AB  - Thomas Linwood Bennett (1868-1932) was one of New York City's first prominent
      physician anesthetists. He was the first dedicated anesthetist at the Hospital
      for the Ruptured and Crippled, subsequently renamed Hospital for Special Surgery.
      He subsequently practiced at multiple institutions throughout New York City as
      one of the first physicians in the United States to dedicate his entire practice
      to the emerging field of anesthesia. Bennett was considered the preeminent
      anesthetist of his time, excelling at research, innovation, education, and
      clinical care. 

PMID- 23960033
TI  - Propofol shares the binding site with isoflurane and sevoflurane on leukocyte
      function-associated antigen-1.
AB  - BACKGROUND: We previously demonstrated that propofol interacted with the
      leukocyte adhesion molecule leukocyte function-associated antigen-1 (LFA-1) and
      inhibited the production of interleukin-2 via LFA-1 in a dependent manner.
      However, the binding site(s) of propofol on LFA-1 remains unknown. METHODS:
      First, the inhibition of LFA-1's ligand binding by propofol was confirmed in an
      enzyme-linked immunosorbent assay (ELISA) ELISA-type assay. The binding site of
      propofol on LFA-1 was probed with a photolabeling experiment using a
      photoactivatable propofol analog called azi-propofol-m. The adducted residues of
      LFA-1 by this compound were determined using liquid chromatography-mass
      spectrometry. In addition, the binding of propofol to the ligand-binding domain
      of LFA-1 was examined using 1-aminoanthracene (1-AMA) displacement assay.
      Furthermore, the binding site(s) of 1-AMA and propofol on LFA-1 was studied using
      the docking program GLIDE. RESULTS: We demonstrated that propofol impaired the
      binding of LFA-1 to its ligand intercellular adhesion molecule-1. The
      photolabeling experiment demonstrated that the adducted residues were localized
      in the allosteric cavity of the ligand-binding domain of LFA-1 called "lovastatin
      site." The shift of fluorescence spectra was observed when 1-AMA was coincubated
      with the low-affinity conformer of LFA-1 ligand-binding domain (wild-type [WT]
      alphaL I domain), not with the high-affinity conformer, suggesting that 1-AMA
      bound only to WT alphaL I domain. In the 1-AMA displacement assay, propofol
      decreased 1-AMA fluorescence signal (at 520 nm), suggesting that propofol
      competed with 1-AMA and bound to the WT alphaL I domain. The docking simulation
      demonstrated that both 1-AMA and propofol bound to the lovastatin site, which
      agreed with the photolabeling experiment. CONCLUSIONS: We demonstrated that
      propofol bound to the lovastatin site in LFA-1. Previously we showed that the
      volatile anesthetics isoflurane and sevoflurane bound to this site. Taken
      together, the lovastatin site is an example of the common binding sites for
      anesthetics currently used clinically.

PMID- 23960036
TI  - Reduction of myocardial infarct size with ischemic "conditioning": physiologic
      and technical considerations.
AB  - A wealth of evidence has revealed that the heart can be "conditioned" and
      rendered less vulnerable to ischemia-reperfusion injury via the upregulation of
      endogenous protective signaling pathways. Three distinct conditioning strategies
      have been identified: (1) preconditioning, the phenomenon where brief episodes of
      myocardial ischemia (too brief to cause cardiomyocyte death) limit necrosis
      caused by a subsequent sustained ischemic insult; (2) postconditioning, the
      concept that relief of myocardial ischemia in a staged or stuttered manner
      attenuates lethal ischemia-reperfusion injury; and (3) remote conditioning, or
      upregulation of a cardioprotective phenotype initiated by ischemia in a remote
      organ or tissue and "transported" to the heart. Progress has been made in
      defining the technical requirements and limitations of each of the 3 ischemic
      conditioning models (including the timing and severity of the protective
      stimulus), as well as elucidating the molecular mechanisms (in particular, the
      receptor-mediated signaling pathways) responsible for conditioning-induced
      myocardial protection. Moreover, phase III clinical trials are in progress,
      seeking to capitalize on the protection that can be achieved by postconditioning
      and remote conditioning, and applying these strategies in patients undergoing
      cardiac surgery or angioplasty for the treatment of acute myocardial infarction.
      There is, however, a potentially important caveat to the clinical translation of
      myocardial conditioning: emerging data suggest that the efficacy of ischemic
      conditioning is compromised in aging, diabetic, and hypertensive cohorts, the
      specific populations in which myocardial protection is most relevant. Successful
      clinical application of myocardial conditioning will therefore require an
      understanding of the potential confounding consequences of these comorbidities on
      the "conditioned" phenotype. 

PMID- 23960037
TI  - A matter of life or limb? A review of traumatic injury patterns and anesthesia
      techniques for disaster relief after major earthquakes.
AB  - BACKGROUND: All modalities of anesthetic care, including conscious sedation,
      general, and regional anesthesia, have been used to manage earthquake survivors
      who require urgent surgical intervention during the acute phase of medical
      relief. Consequently, we felt that a review of epidemiologic data from major
      earthquakes in the context of urgent intraoperative management was warranted to
      optimize anesthesia disaster preparedness for future medical relief operations.
      The primary outcome measure of this study was to identify the predominant
      preoperative injury pattern (anatomic location and pathology) of survivors
      presenting for surgical care immediately after major earthquakes during the acute
      phase of medical relief (0-15 days after disaster). The injury pattern is of
      significant relevance because it closely relates to the anesthetic techniques
      available for patient management. We discuss our findings in the context of
      evidence-based strategies for anesthetic management during the acute phase of
      medical relief after major earthquakes and the associated obstacles of devastated
      medical infrastructure. METHODS: To identify reports on acute medical care in the
      aftermath of natural disasters, a query was conducted using MEDLINE/PubMed,
      Embase, CINAHL, as well as an online search engine (Google Scholar). The search
      terms were "disaster" and "earthquake" in combination with "injury," "trauma,"
      "surgery," "anesthesia," and "wounds." Our investigation focused only on studies
      of acute traumatic injury that specified surgical intervention among survivors in
      the acute phase of medical relief. RESULTS: A total of 31 articles reporting on
      15 major earthquakes (between 1980 and 2010) and the treatment of more than
      33,410 patients met our specific inclusion criteria. The mean incidence of
      traumatic limb injury per major earthquake was 68.0%. The global incidence of
      traumatic limb injury was 54.3% (18,144/33,410 patients). The pooled estimate of
      the proportion of limb injuries was calculated to be 67.95%, with a 95%
      confidence interval of 62.32% to 73.58%. CONCLUSIONS: Based on this analysis,
      early disaster surgical intervention will focus on surviving patients with limb
      injury. All anesthetic techniques have been safely used for medical relief. While
      regional anesthesia may be an intuitive choice based on these findings, in the
      context of collapsed medical infrastructure, provider experience may dictate the
      available anesthetic techniques for earthquake survivors requiring urgent
      surgery.

PMID- 23960035
TI  - The hemodynamic response to dexmedetomidine loading dose in children with and
      without pulmonary hypertension.
AB  - BACKGROUND: Dexmedetomidine, an alpha-2 receptor agonist, is widely used in
      children with cardiac disease. Significant hemodynamic responses, including
      systemic and pulmonary vasoconstriction, have been reported after dexmedetomidine
      administration. Our primary goal of this prospective, observational study was to
      quantify the effects of dexmedetomidine initial loading doses on mean pulmonary
      artery pressure (PAP) in children with and without pulmonary hypertension.
      METHODS: Subjects were children undergoing cardiac catheterization for either
      routine surveillance after cardiac transplantation (n = 21) or pulmonary
      hypertension studies (n = 21). After anesthetic induction with sevoflurane and
      tracheal intubation, sevoflurane was discontinued and anesthesia was maintained
      with midazolam 0.1 mg/kg i.v. (or 0.5 mg/kg orally preoperatively) and
      remifentanil i.v. infusion 0.5 to 0.8 MUg/kg/min. Ventilation was mechanically
      controlled to maintain PCO2 35 to 40 mm Hg. When end-tidal sevoflurane was 0% and
      fraction of inspired oxygen (FIO2) was 0.21, baseline heart rate, mean arterial
      blood pressure, PAP, right atrial pressure, pulmonary artery occlusion pressure,
      right ventricular end-diastolic pressure, cardiac output, and arterial blood
      gases were measured, and indexed systemic vascular resistance, indexed pulmonary
      vascular resistance, and cardiac index were calculated. Each subject then
      received a 10-minute infusion of dexmedetomidine of 1 MUg/kg, 0.75 MUg/kg, or 0.5
      MUg/kg. Measurements and calculations were repeated at the conclusion of the
      infusion. RESULTS: Most hemodynamic responses were similar in children with and
      without pulmonary hypertension. Heart rate decreased significantly, and mean
      arterial blood pressure and indexed systemic vascular resistance increased
      significantly. Cardiac index did not change. A small, statistically significant
      increase in PAP was observed in transplant patients but not in subjects with
      pulmonary hypertension. Changes in indexed pulmonary vascular resistance were not
      significant. CONCLUSION: Dexmedetomidine initial loading doses were associated
      with significant systemic vasoconstriction and hypertension, but a similar
      response was not observed in the pulmonary vasculature, even in children with
      pulmonary hypertension. Dexmedetomidine does not appear to be contraindicated in
      children with pulmonary hypertension.

PMID- 23960038
TI  - Low-Pt loaded on a vanadium nitride/graphitic carbon composite as an efficient
      electrocatalyst for the oxygen reduction reaction.
AB  - The high cost of platinum electrocatalysts for the oxygen reduction reaction
      (ORR) has hindered the commercialization of fuel cells. An effective support can
      reduce the usage of Pt and improve the reactivity of Pt through synergistic
      effects. Herein, the vanadium nitride/graphitic carbon (VN/GC) nanocomposites,
      which act as an enhanced carrier of Pt nanoparticles (NPs) towards ORR, have been
      synthesized for the first time. In the synthesis, the VN/GC composite could be
      obtained by introducing VO3 (-) and [Fe(CN)6 ](4-) ions into the polyacrylic weak
      acid anion-exchanged resin (PWAR) through an in-situ anion-exchanged route,
      followed by carbonization and a subsequent nitridation process. After loading
      only 10 % Pt NPs, the resulting Pt-VN/GC catalyst demonstrates a more positive
      onset potential (1.01 V), higher mass activity (137.2 mA mg(-1) ), and better
      cyclic stability (99 % electrochemical active surface area (ECSA) retention after
      2000 cycles) towards ORR than the commercial 20 % Pt/C. Importantly, the Pt-VN/GC
      catalyst mainly exhibits a 4 e(-) -transfer mechanism and a low yield of peroxide
      species, suggesting its potential application as a low-cost and highly efficient
      ORR catalyst in fuel cells. 

PMID- 23960039
TI  - Association of musculoskeletal complaints and gliptin use: review of spontaneous
      reports.
AB  - PURPOSE: Gliptins are new oral antidiabetic drugs that increase insulin levels
      through dipeptidyl peptidase-4 inhibition. Recently, the association of serious
      musculoskeletal (MSk) adverse effects with the gliptin use has been suggested.
      The aim is to describe and analyze the characteristics of spontaneous reports
      related to these adverse effects and gliptin use. METHODS: All spontaneous
      reports with MSk disorders associated with gliptins gathered in the Spanish
      pharmacovigilance database until May 2012 were described and analyzed using a
      case/non-case method. RESULTS: Gliptins were reported as the suspected drug in
      332 cases: 208 involved sitagliptin, 115 vildagliptin, and nine saxagliptin. In
      34 patients (10.2% of total reports with gliptins), MSk reactions were described
      (22 women [64.7%] and 12 men [35.3%]). Their mean age was 65.1 years; 41.2% were
      younger than 65 years. Only seven cases were serious, but the gliptin had to be
      withdrawn in 22 patients because of intolerance and/or persistence of MSk
      discomfort, and patients recovered after its discontinuation. A positive re
      challenge was observed in two cases. In seven cases, the patients were on
      previous chronic treatment with statins, and began to present MSk complaints
      shortly after starting a gliptin. The reporting odds ratio (ROR) for myalgia and
      arthralgia were strongly associated with gliptin use (ROR 1.96 [95% CI 1.12
      3.43], p < 0.05 and ROR 2.69 [95% CI 1.38-5.24], p < 0.05, respectively).
      CONCLUSIONS: Musculoskeletal disorders are adverse reactions strongly associated
      with gliptins that, despite not being serious, may impair the treatment adherence
      in patients with type 2 diabetes. Future observational studies could confirm
      these findings.

PMID- 23960040
TI  - Author response: Human corneal endothelium regeneration: effect of ROCK
      Inhibitor.

PMID- 23960041
TI  - Extrahepatic implications of metabolic syndrome.

PMID- 23960042
TI  - Cfr-mediated linezolid resistance in methicillin-resistant Staphylococcus aureus
      and Staphylococcus haemolyticus associated with clinical infections in humans:
      two case reports.

PMID- 23960043
TI  - When the precautionary principle disrupts 3 years of antibiotic stewardship:
      nitrofurantoin in the treatment of urinary tract infections.

PMID- 23960044
TI  - Nutrient reserves may allow for genome size increase: evidence from comparison of
      geophytes and their sister non-geophytic relatives.
AB  - BACKGROUND AND AIMS: The genome size of an organism is determined by its capacity
      to tolerate genome expansion, given the species' life strategy and the limits of
      a particular environment, and the ability for retrotransposon suppression and/or
      removal. In some giant-genomed bulb geophytes, this tolerance is explained by
      their ability to pre-divide cells in the dormant stages or by the selective
      advantage of larger cells in the rapid growth of their fleshy body. In this
      study, a test shows that the tendency for genome size expansion is a more
      universal feature of geophytes, and is a subject in need of more general
      consideration. METHODS: Differences in monoploid genome sizes were compared using
      standardized phylogenetically independent contrasts in 47 sister pairs of
      geophytic and non-geophytic taxa sampled across all the angiosperms. The genome
      sizes of 96 species were adopted from the literature and 53 species were newly
      measured using flow cytometry with propidium iodide staining. KEY RESULTS: The
      geophytes showed increased genome sizes compared with their non-geophytic
      relatives, regardless of the storage organ type and regardless of whether or not
      vernal geophytes, polyploids or annuals were included in the analyses.
      CONCLUSIONS: The universal tendency of geophytes to possess a higher genome size
      suggests the presence of a universal mechanism allowing for genome expansion. It
      is assumed that this is primarily due to the nutrient and energetic independence
      of geophytes perhaps allowing continuous synthesis of DNA, which is known to
      proceed in the extreme cases of vernal geophytes even in dormant stages. This
      independence may also be assumed as a reason for allowing large genomes in some
      parasitic plants, as well as the nutrient limitation of small genomes of
      carnivorous plants.

PMID- 23960045
TI  - Reproductive differentiation into sexual and apomictic polyploid cytotypes in
      Potentilla puberula (Potentilleae, Rosaceae).
AB  - BACKGROUND AND AIMS: Intraspecific reproductive differentiation into sexual and
      apomictic cytotypes of differing ploidy is a common phenomenon. However,
      mechanisms enabling the maintenance of both reproductive modes and integrity of
      cytotypes in sympatry are as yet poorly understood. This study examined the
      association of sexual and apomictic seed formation with ploidy as well as gene
      flow towards sexuals within populations of purely polyploid Potentilla puberula.
      METHODS: The study is based on 22 populations representing various combinations
      of five polyploid cytotypes (tetraploid-octoploid) from East Tyrol, Austria.
      Embryo ploidy and the endosperm/embryo ploidy ratio obtained by a flow cytometric
      seed screen were used to infer reproductive modes of seed formation and to
      calculate the male and female genomic contributions to the embryo and endosperm.
      Self-incompatibility (SI) patterns were assessed and a new indirect approach was
      used to test for the occurrence of intercytotype matings based on the variation
      in the male genomic contribution to sexually derived embryos on the level of
      developed seed. KEY RESULTS: Tetraploids formed seeds almost exclusively via
      sexual reproduction, whereas penta- to octoploids were preferentially apomictic.
      Non-random distribution of reproductive modes within maternal plants further
      revealed a tendency to separate the sexual from the apomictic mode among
      individuals. Self-incompatibility of sexuals indicated functionality of the
      gametophytic SI system despite tetraploidy of the nuclear genome. We found no
      indication for significant cross-fertilization of tetraploids by the high
      polyploids. CONCLUSIONS: The study revealed a rare example of intraspecific
      differentiation into sexual and apomictic cytotypes at the polyploid level. The
      integrity of the sexual tetraploids was maintained due to reproductive isolation
      from the apomictic higher polyploids. Functionality of the gametophytic SI system
      suggested that the tetraploids are functional diploids.

PMID- 23960046
TI  - Silica nanoparticles aid in structural leaf coloration in the Malaysian tropical
      rainforest understorey herb Mapania caudata.
AB  - BACKGROUND AND AIMS: Blue-green iridescence in the tropical rainforest
      understorey sedge Mapania caudata creates structural coloration in its leaves
      through a novel photonic mechanism. Known structures in plants producing
      iridescent blues consist of altered cellulose layering within cell walls and in
      special bodies, and thylakoid membranes in specialized plastids. This study was
      undertaken in order to determine the origin of leaf iridescence in this plant
      with particular attention to nano-scale components contributing to this
      coloration. METHODS: Adaxial walls of leaf epidermal cells were characterized
      using high-pressure-frozen freeze-substituted specimens, which retain their
      native dimensions during observations using transmission and scanning microscopy,
      accompanied by energy-dispersive X-ray spectroscopy to identify the role of
      biogenic silica in wall-based iridescence. Biogenic silica was experimentally
      removed using aqueous Na2CO3 and optical properties were compared using spectral
      reflectance. KEY RESULTS AND CONCLUSIONS: Blue iridescence is produced in the
      adaxial epidermal cell wall, which contains helicoid lamellae. The blue
      iridescence from cell surfaces is left-circularly polarized. The position of the
      silica granules is entrained by the helicoid microfibrillar layers, and granules
      accumulate at a uniform position within the helicoids, contributing to the
      structure that produces the blue iridescence, as part of the unit cell
      responsible for 2  degrees  Bragg scatter. Removal of silica from the walls
      eliminated the blue colour. Addition of silica nanoparticles on existing
      cellulosic lamellae is a novel mechanism for adding structural colour in
      organisms.

PMID- 23960047
TI  - Dry sampling of gas-phase isocyanates and isocyanate aerosols from thermal
      degradation of polyurethane.
AB  - The performance of a dry sampler, with an impregnated denuder in series with a
      glass fibre filter, using di-n-butylamine (DBA) for airborne isocyanates (200ml
      min(-1)) is investigated and compared with an impinger flask with a glass fibre
      filter in series (1 l min(-1)). An exposure chamber containing 1,6-hexamethylene
      diisocyanate (HDI), isophorone diisocyanate (IPDI), and 2,4- and 2,6-toluene
      diisocyanate (TDI) in the concentration range of 5-205 MUg m(-3) [0.7-33 p.p.b.;
      relative humidity (RH) 50%], generated by gas- and liquid-phase permeation, was
      used for the investigation. The precision for the dry sampling for five series
      with eight samplers were in the range of 2.0-6.1% with an average of 3.8%. During
      120-min sampling (n = 4), no breakthrough was observed when analysing samplers in
      series. Sixty-four exposed samplers were analysed after storage for 0, 7, 14, and
      21 days. No breakdown of isocyanate derivatives was observed. Twenty-eight
      samplers in groups of eight were collecting isocyanates during 0.5-32h. Virtually
      linear relationships were obtained with regard to sampling time and collected
      isocyanates with correlation coefficients in the range of 0.998-0.999 with the
      intercept close to the origin. Pre- or post-exposure to ambient air did not
      affect the result. Dry sampling (n = 48) with impinger-filter sampling (n = 48)
      of thermal decomposition product of polyurethane polymers, at RH 20, 40, 60, and
      90%, was compared for 11 isocyanate compounds. The ratio between the different
      isocyanates collected with dry samplers and impinger-filter samplers was in the
      range of 0.80-1.14 for RH = 20%, 0.8-1.25 for RH = 40%, 0.76-1.4 for RH = 60%,
      and 0.72-3.7 for RH = 90%. Taking into account experimental errors, it seems
      clear that isocyanic acid DBA derivatives are found at higher levels in the dry
      samples compared with impinger-filter samplers at elevated humidity. The dry
      sampling using DBA as the reagent enables easy and robust sampling without the
      need of field extraction. 

PMID- 23960048
TI  - Withholding artificial nutrition and hydration.

PMID- 23960050
TI  - Intravitreal bevacizumab for the treatment of retinopathy of prematurity: a case
      report.
AB  - OBJECTIVE: We report the first case in Scotland of a premature infant treated for
      retinopathy of prematurity with bevacizumab. METHOD: A case report and a review
      of the literature are presented. RESULTS: Retinopathy of prematurity is a leading
      worldwide cause of childhood blindness. Conventional laser treatment results in
      destruction of the peripheral retina and does not prevent all cases of vision
      loss, particularly in Zone I disease. We present the case of a baby born at
      26(+3) weeks who developed stage 3+ disease located in Zone I of the retina. The
      patient was treated with bilateral bevacizumab injections and achieved complete
      resolution of his retinopathy. CONCLUSION: Bevacizumab therapy for the treatment
      of retinopathy of prematurity is an effective and inexpensive treatment that can
      readily and quickly be administered by a competent ophthalmologist without the
      need for specialist equipment.

PMID- 23960052
TI  - The suspected scaphoid injury: resource implications in the absence of magnetic
      resonance imaging.
AB  - INTRODUCTION: Undiagnosed and untreated scaphoid fractures have poorer outcomes
      and many patients are unnecessarily immobilised for prolonged periods of time to
      avoid missing occult injuries. Magnetic resonance imaging has a high sensitivity
      and specificity in detecting occult scaphoid fractures, but many units do not
      routinely use this imaging modality in the diagnostic pathway. We aimed to
      determine the patterns of suspected scaphoid injuries, report the process of
      care, and calculate the costs involved in their management. METHODS: We
      prospectively identified all adult patients referred to fracture clinic at the
      Royal Infirmary of Edinburgh with a scaphoid-related injury, between October 2007
      and September 2008. Clinical notes were examined retrospectively. We defined
      three injury groups: true fractures, occult fractures, and suspected scaphoid
      injuries. We analysed patient demographics, treatment timelines, and the
      treatment costs involved. RESULTS: Fracture clinic received 537 scaphoid-related
      referrals. There were 87 true fractures, 43 occult fractures, and 407 suspected
      injuries, incurring average treatment costs of L1,173, L773, and L384
      respectively. Occult fractures accounted for 33% of all confirmed scaphoid
      fractures. The majority of scaphoid-related referrals (76%) were never proven to
      have a scaphoid fracture, and many were unnecessarily immobilised. The costs
      involved in the treatment of suspected scaphoid injuries were found to be higher
      than the cost of magnetic resonance imaging (L97). CONCLUSION: In this group of
      suspected scaphoid injury, we believe the introduction of an early magnetic
      resonance imaging protocol would lead to an earlier definitive diagnosis and
      potentially a more cost-effective service.

PMID- 23960051
TI  - The effect of magnesium administration on erythrocyte transketolase activity in
      alcoholic patients treated with thiamine.
AB  - BACKGROUND AND AIMS: Chronic alcoholic patients are at increased risk of
      developing deficiencies of thiamine and magnesium. Thiamine is an essential co
      factor for a number of enzymes involved in carbohydrate metabolism and requires
      optimal levels of magnesium for biological function. However, whilst thiamine
      supplementation is well established for the treatment of alcoholic patients, the
      importance of magnesium is often overlooked. We describe the effect of concurrent
      thiamine and magnesium administration on the activity of the thiamine-dependent
      enzyme erythrocyte transketolase in a cohort of chronic alcoholic patients.
      METHODS: Baseline erythrocyte transketolase activities were measured on blood
      samples collected from 36 chronic alcoholic patients presenting acutely to the
      Accident and Emergency department. Patients received either intravenous Pabrinex
      (thiamine) supplemented with magnesium sulphate (n = 18) or Pabrinex only (n =
      18). Post-treatment bloods were collected for re-assessment of erythrocyte
      transketolase activity. The change in transketolase activities (pre-vs. post
      treatment) between the two patient groups were compared by Mann-Whitney U test.
      RESULTS: The increase in transketolase activity following treatment in the cohort
      receiving Pabrinex supplemented with magnesium sulphate was significantly greater
      (p = 0.018) than that produced in the cohort receiving Pabrinex alone.
      CONCLUSION: In the acute management of a sample of chronic alcoholic patients,
      those receiving magnesium sulphate with Pabrinex have higher increases in
      erythrocyte transketolase activity compared with those receiving Pabrinex alone.
      We conclude that concurrent magnesium administration with Pabrinex may be
      required for enabling full efficacy of Pabrinex treatment, as demonstrated by its
      positive effect on erythrocyte transketolase activity.

PMID- 23960053
TI  - The epidemiology and management of adult poisonings admitted to the short-stay
      ward of a large Scottish emergency department.
AB  - BACKGROUND AND AIMS: The emergency department of Aberdeen Royal Infirmary
      receives around 68,000 new adult admissions annually. All poisoning cases are
      admitted to a 14-bedded short-stay ward, except those admitted to intensive care
      or immediately discharged. This study aimed to analyse epidemiological trends and
      management of short-stay ward admissions for poisonings. METHOD AND RESULTS:
      Adult (>13 years) poisoning presentations admitted to the emergency department
      short-stay ward of Aberdeen Royal Infirmary from 1 January-31 December 2009 were
      retrospectively reviewed using patient discharge summaries. During 2009, there
      were 1062 poisoning cases, of which repeat episodes were responsible for 15%. The
      mean age of presentation was 33.9 years (SD 14.4) and there was a female
      preponderance (62%). Almost half of poisonings were polypharmacy, alcohol was
      involved in 40% of cases and overdoses most commonly involved paracetamol (43%).
      Management involved basic observations only (66%), N-acetylcysteine (24%),
      naloxone (4%) and activated charcoal (1%). Liaison psychiatry reviewed 84%
      presentations and admitted 9% to the psychiatric unit. CONCLUSIONS: The short
      stay ward is important for acute management of poisonings and the data gained
      from this study should help to direct patient services appropriately.

PMID- 23960054
TI  - The role of 18F-fluoro-2-deoxyglucose positron emission tomography/computed
      tomography in the management of patients with carcinoma of unknown primary.
AB  - PURPOSE: Carcinoma of unknown primary is one of the ten most frequent cancers
      worldwide. Its median survival time is less than 10 months. Detecting primary
      tumour locations and/or occult metastatic lesions may inform definitive treatment
      and improve patients' prognosis. We aimed to determine: (1) the sensitivity,
      specificity and accuracy of (18)F-fluoro-2-deoxyglucose positron emission
      tomography/computed tomography; (2) its detection rate of primary tumour
      locations and occult metastases and (3) factors associated with improved survival
      times. METHODS: We retrospectively reviewed all cases in the West of Scotland for
      the period 1 December 2007 to 31 May 2011 that met all our selection criteria:
      (1) diagnosis of carcinoma of unknown primary; (2) a thorough but negative 'work
      up' and (3) (18)F-fluoro-2-deoxyglucose positron emission tomography/computed
      tomography report. Statistical methods included frequencies, Kaplan-Meier graphs
      and log-rank tests to compare survival times. RESULTS: (18)F-fluoro-2
      deoxyglucose positron emission tomography/computed tomography detected primary
      tumour sites in 19/51 (37.3%) and occult metastases in 28/51 (54.9%) of eligible
      patients. Its sensitivity, specificity and accuracy were 79.2%, 70.4% and 74.5%,
      respectively; 20/51 (39.2%) patients died during the study period with a median
      survival of 8.4 months (range 21.4, SD +/- 6.2). The number of metastatic
      locations was strongly associated with survival (p = 0.002), but detection of a
      primary tumour site (p = 0.174) or histopathology (p = 0.301) was not.
      CONCLUSION: (18)F-fluoro-2-deoxyglucose positron emission tomography/computed
      tomography detected occult metastatic sites in the majority and a primary cancer
      location in a substantial minority of patients. Our results were comparable with
      international literature and may indicate that (18)F-fluoro-2-deoxyglucose
      positron emission tomography/computed tomography have an early role to improve
      the accuracy of cancer staging and to optimise carcinoma of unknown primary
      management.

PMID- 23960055
TI  - A systematic review of plate versus intramedullary fixation in the treatment of
      midshaft clavicle fractures.
AB  - The best method of fixation for clavicle fractures is not known. The purpose of
      this review was to examine the evidence comparing plate and intramedullary
      fixation for midshaft clavicle fractures. A search of MEDLINE in September 2011
      identified five papers that compared plate and intramedullary fixation, and
      fulfilled our eligibility criteria, consisting of; one randomised controlled
      trial, two quasi-randomised controlled trials, and two retrospective studies.
      Level of evidence was assessed using the Scottish Intercollegiate Guidelines
      Network guidance and the Cochrane Bone, Joint and Muscle Trauma Group's quality
      assessment tool. No attempt at meta-analysis was made due to the heterogeneity of
      the study populations and interventions. We found no difference between
      intramedullary fixation and plate fixation. There was a trend towards a lower
      complication rate with intramedullary fixation. On the basis of the available
      evidence, we would advocate both techniques for the treatment of midshaft
      clavicle fractures. 

PMID- 23960056
TI  - Direct access colonoscopy in primary care: is it a safe and practical approach?
AB  - BACKGROUND: Implementation of colorectal cancer screening programme and provision
      of cancer service within certain timeframe has significantly increased the
      workload on endoscopy services. Direct access colonoscopy in primary care centers
      helps offload burden on conventional colonoscopy in secondary care, thereby
      reducing waiting times. The aim of this study was to assess the safety and
      efficacy of direct access colonoscopy service. MATERIALS AND METHODS: Provision
      of colonoscopy service in our healthcare trust was analysed retrospectively
      during a two-year period. Safety and feasibility of direct access colonoscopy was
      analysed against conventional colonoscopy. The groups were compared for findings
      at colonoscopy, procedural outcomes, and complications. RESULTS: A total of 3468
      colonoscopies were analysed. Of those, 1189(34.3%) were performed as direct
      access colonoscopy and 2279(65.7%) as conventional colonoscopy. No abnormality
      was detected in 408/1189(34.3%) and 825/2279(36.2%) patients in the direct access
      colonoscopy and conventional colonoscopy groups, respectively (p = 0.52).
      Colorectal cancer detection rate was similar between the groups; conventional
      colonoscopy vs direct access colonoscopy, 3.1% (68/2279) vs 3.2% (39/1189) (p =
      0.85). However, there was significantly higher detection rate of polyps greater
      than 1 cm in conventional colonoscopy group compared to direct access colonoscopy
      group, 22.6%(518/2289) vs 12.6% (150/1189) (p = 0.02). Complication rates were
      comparable between the groups. CONCLUSION: Direct access colonoscopy in primary
      care centers is safe and feasible. Colorectal cancer detection remains comparable
      to that of conventional colonoscopy in secondary care despite relatively lower
      polyp detection rate.

PMID- 23960057
TI  - Missed opportunities for HIV diagnosis: a three-year audit in the West of
      Scotland.
AB  - BACKGROUND: National specialty guidelines for HIV testing aim to increase
      diagnosis and reduce late presentation. An audit of new HIV diagnoses in Glasgow
      was performed to assess local performance against these guidelines and estimate
      the proportion of patients presenting who had previous missed opportunities for
      diagnosis. METHODS: A retrospective case note review of 339 patients diagnosed
      from September 2008 to September 2011 was performed. Documented past medical
      history was assessed for HIV clinical indicator conditions prior to HIV diagnosis
      and prior review by medical services. RESULTS: Ninety (26%) individuals had at
      least one documented clinical indicator condition prior to HIV diagnosis, of whom
      80 had prior contact with at least one speciality. This group also had a lower
      mean nadir CD4 count (258 cells/cmm versus 393 cells/cmm, p = <0.005) and were
      more likely to be severely immunocompromised at diagnosis, with a CD4 count below
      50 cells/cmm (31% versus 9%, p = <0.005). AIDS-defining illnesses were also more
      common (31% versus 8%, p <= 0.005) as was HIV-related mortality (p <= 0.005).
      CONCLUSION: Additional support and training are required to increase adherence to
      HIV-testing guidelines within primary and secondary care in order to prevent
      ongoing late presentation with both individual clinical and public health
      implications.

PMID- 23960058
TI  - Hepatitis E: the West of Scotland experience.
AB  - BACKGROUND AND AIMS: Hepatitis E virus is traditionally regarded as a virus of
      the developing world and is emerging as a leading cause of non-A/B/C hepatitis.
      We wished to investigate locally acquired transmission of hepatitis E in the West
      of Scotland and compare our use of traditional serology versus polymerase chain
      reaction since the introduction of polymerase chain reaction in 2007. METHODS:
      Clinical details provided on specimens of blood positive for hepatitis E virus by
      serology or polymerase chain reaction were collated and analysed. RESULTS: Since
      2007, 30 samples were hepatitis E virus-positive by serology or polymerase chain
      reaction. Polymerase chain reaction positivity was generally associated with
      positive serology although four samples were polymerase chain reaction-negative
      and strongly positive by serology. Interestingly, one-quarter of cases were
      likely to represent endogenous transmission of the infection. CONCLUSIONS:
      Polymerase chain reaction is valuable in reliably diagnosing hepatitis E virus.
      However, serology is valuable for diagnosing resolved infection. There may be a
      high level of undiagnosed locally acquired hepatitis E virus in Scotland.

PMID- 23960059
TI  - Nineteenth century mortality at the Royal Hospital for Sick Children, Glasgow.
AB  - BACKGROUND AND AIMS: Since Glasgow's Royal Hospital for Sick Children opened in
      1882, significant advances have been made in child health. Our aim was to
      investigate the hospital mortality that occurred in the last decade of the 19th
      century at Royal Hospital for Sick Children. METHODS AND RESULTS: Hospital
      mortality records for the decades, 1890-1899, were collected from the Archives of
      the Royal Hospital for Sick Children. Data were extracted from the hospital
      inpatient records and the pathology records. In the decade 1890-1899, there were
      731 hospital deaths. The main cause of death at that time in the 19th Century was
      infection, particularly of the respiratory tract. The age at which death occurred
      was analysed and the recorded cause were analysed as was the distance patients
      travelled to the hospital. The ratio of boys to girls and length of inpatient
      stay was similar to that seen in the hospital currently. CONCLUSION: This study
      records the mortality in a children's hospital in a large developing industrial
      city in the 19th century as experienced in a children's hospital.

PMID- 23960060
TI  - Perceived tutor benefits of teaching near peers: insights from two near peer
      teaching programmes in South East Scotland.
AB  - BACKGROUND AND AIMS: There is little evidence about the benefits to junior
      doctors of participating in teaching, or how to train doctors as teachers. We
      explore (through South East Scotland based teaching programmes): (a) How prepared
      do junior doctors feel to teach? (b) What junior doctors consider to be the main
      challenges of teaching? (c) What motivates the junior doctors to continue
      teaching, and what is the perceived impact of teaching on their professional
      development? METHODS AND RESULTS: 'Questionnaire 1', distributed at 'tutor
      training days', explored (i) attitudes towards teaching and (ii) tutors'
      preparedness to teach. 'Questionnaire 2', distributed after completion of a
      teaching programme, evaluated the tutor experience of teaching. RESULTS: Seventy
      six per cent of tutors reported no previous teacher training; 10% were able to
      teach during allocated work hours. The strongest motivation for teaching was to
      help students with their learning and to develop teaching skills. Ninety one per
      cent of tutors felt more prepared to teach by the end of the programme. Tutors
      also improved their clinical skills from teaching. CONCLUSIONS: There is a body
      of junior doctors, who see teaching as an important part of their career,
      developing both teaching and clinical skills in the tutor. If teaching is
      expected of foundation doctors, rotas ought to be more flexible to facilitate
      both teaching and teacher training.

PMID- 23960061
TI  - The treatment of retinopathy of prematurity.

PMID- 23960062
TI  - Bilateral Morgagni hernia: operative discovery of appendix lying on superior
      pulmonary vein.
AB  - A patient presented having an acute abdomen on a background of a twelve-month
      history of worsening asthma. Computed tomography showed giant bilateral
      intrathoracic hernias extending to both thoracic apices. Our case was unusual as
      the defect was bilateral and left-sided. Surgical repair revealed each hernia sac
      measuring >20 cm and to contain the entirety of the small bowel and colon
      (including retroperitoneal bowel). The appendix was discovered adjacent to right
      superior pulmonary vein. Both sacs were excised and the defects dissected and
      transfixed in a single stage operation. In the post-operative stage, he developed
      a 6.3 cm fluid collection anterior to the right atrium and a left-sided pleural
      effusion. Morgagni hernias can escape detection and be attributed to other
      diagnoses courtesy of false localising signs on clinical examination and symptoms
      in the history. 

PMID- 23960063
TI  - Cozen's phenomenon: a reminder.
AB  - A four-year-old child attended Accident and Emergency following a fall from a
      slide with a displaced and angulated proximal tibial metaphyseal fracture.
      Treatment included closed manipulation under anaesthesia and an above knee cast
      for seven weeks. Serial radiographs over the following few months were
      satisfactory demonstrating good alignment and evidence of healing. However, at
      four-months review new-onset genu valgum with mechanical axis deviation was
      noted. No evidence of spontaneous resolution was noted over the following 12
      months and hence a corrective hemi-epiphysiodesis was performed. At 12-months
      post-operatively, there was marked clinical and radiographical improvement in
      alignment. Classically Cozen's phenomenon is described as the late-onset post
      traumatic valgus deformity associated with proximal tibial metaphyseal fractures
      in children. We want to reemphasise the early recognition of children at risk of
      this unique complication. In addition, we wish to highlight the progression of
      the late-onset valgus and its subsequent management. 

PMID- 23960064
TI  - Dipyridamole and paracetamol overdose resulting in multi-organ failure.
AB  - Dipyridamole intoxication is rare and few reports exist amongst the current
      literature. A case of dipyridamole and paracetamol overdose is described in a
      previously healthy 58-year-old woman, which resulted in multi-organ failure
      requiring dialysis, inotropic support, ventilation and extensive surgical
      intervention for small bowel ischaemia. This case highlights the dangers of an
      unusually large overdose of a commonly prescribed drug, and reviews current
      knowledge of dipyridamole intoxication. 

PMID- 23960065
TI  - Neonatal hip septic arthritis: ultrasound should not influence decision to
      aspirate.
AB  - An 18-week-old boy presented to the emergency department with 24-h history of
      fever and irritability with a painful left hip held in flexion. Blood tests
      showed an elevated ESR of 65 mm/h, but white cell count and C-reactive protein
      were in the reference range. Admission hip ultrasound identified a small effusion
      (<2 mm at the recess), not large enough to determine turbidity. Joint aspiration
      under general anaesthesia yielded frank pus and mandated open arthrotomy.
      Physicians must maintain a high index of suspicion of hip septic arthritis
      irrespective of ultrasound findings and have a low threshold for joint
      aspiration. Aspiration 'to dryness' would have left substantial pus within the
      joint and is consistent with advocating arthrotomy and washout in this age group,
      when the diagnosis of septic arthritis has been made. 

PMID- 23960066
TI  - Conservative management of laryngeal dog bite.
AB  - BACKGROUND AND AIMS: Dog bites represent an important public health issue,
      causing injuries from trivial to fatal. The true incidence is unknown due to the
      lack of national and local reporting system. School children, mostly male, are
      more commonly affected with the majority of injuries occurring in the head and
      neck area, followed by the limbs and trunk. METHODS: The conservative management
      of a 6-year-old girl who sustained a fracture of her laryngeal structure from an
      attack by her neighbours' dog is described. Only a 1 cm visible puncture wound in
      the midline of her neck with air escaping through the wound was seen at
      presentation. RESULTS: Ten days were spent in hospital including the first four
      in intubated Paediatric Intensive Care Unit. Initial microlaryngoscopy and
      bronchoscopy (MLB) showed a swelling in the right anterior subglottis not
      reducible by manipulation. She was re-intubated with progressively larger naso
      tracheal tube until the fracture was fully reduced on her 3rd MLB. Three months
      post-injury, there is no evidence of airway narrowing. CONCLUSION: The literature
      advocates early surgical management of laryngeal trauma including dog bites.
      Conservative management of laryngeal fracture from a dog bite is feasible and
      associated with a good outcome and no long-term sequela.

PMID- 23960067
TI  - Two isolated giant gastric duplication cysts in thorax in a newborn.
AB  - We report a case of a newborn with severe respiratory distress since birth with
      two giant intrathoracic and separate eneteric duplication cysts in right
      hemithorax. On day 19, the intrathoracic cysts were removed, and the baby was
      discharged on his 22nd day of life. Histologic findings confirmed the diagnosis
      of a gastric duplication cyst. This report is the first case of two isolated,
      separated and giant right intrathoracic gastric duplication cysts in literature.
      The diagnostic values of radiological evaluation and surgical and pathological
      management for precise diagnosis are discussed. 

PMID- 23960068
TI  - Acute myocardial infarction in pregnancy following unlicensed use of
      methylenedioxymethamphetamine ('Ecstasy').
AB  - Acute myocardial infarction is rare in pregnancy; however, the emerging trend
      towards advanced maternal age and the rising prevalence of obesity and diabetes
      suggest that more cases of myocardial infarction are likely to be encountered in
      pregnancy. However, there is scanty evidence on the risk of myocardial infarction
      with regard to socially misused substances in pregnancy. We describe the
      management of a case of acute myocardial infarction following unlicensed use of
      3,4-methylenedioxymethamphetamine ('Ecstasy') in pregnancy. The case highlights a
      rare but serious risk associated with substance misuse in pregnancy. 

PMID- 23960069
TI  - Improvement in symptoms of peripheral arterial disease with sildenafil therapy.
AB  - A 57-year-old man presented with symptoms of intermittent claudication and was
      diagnosed with peripheral arterial disease. He was advised to stop smoking and
      start a walking programme. He had a background history of hypercholesterolaemia
      and erectile dysfunction, for which he was taking simvastatin and
      phosphodiesterase type-5 inhibitor sildenafil, respectively. After starting his
      exercise programme, he noted that his walking distance was more than doubled on
      the mornings after taking sildenafil, and he has been using sildenafil primarily
      for shopping trips since that time. Although this single-patient self-experiment
      has the potential for placebo confounding, the patient was not led to expect this
      benefit, and there is evidence that reduced nitric oxide bioactivity plays an
      important role in the pathophysiology of peripheral arterial disease. Given the
      biological plausibility of this effect, we feel that a randomised, blinded and
      placebo-controlled clinical study is warranted to confirm the benefit of
      phosphodiesterase type-5 inhibitors in peripheral arterial disease. 

PMID- 23960070
TI  - Dynein interacts with the neural cell adhesion molecule (NCAM180) to tether
      dynamic microtubules and maintain synaptic density in cortical neurons.
AB  - Cytoplasmic dynein is well characterized as an organelle motor, but dynein also
      acts to tether and stabilize dynamic microtubule plus-ends in vitro. Here we
      identify a novel and direct interaction between dynein and the 180-kDa isoform of
      the neural cell adhesion molecule (NCAM). Optical trapping experiments indicate
      that dynein bound to beads via the NCAM180 interaction domain can tether
      projecting microtubule plus-ends. Live cell assays indicate that the NCAM180
      dependent recruitment of dynein to the cortex leads to the selective
      stabilization of microtubules projecting to NCAM180 patches at the cell
      periphery. The dynein-NCAM180 interaction also enhances cell-cell adhesion in
      heterologous cell assays. Dynein and NCAM180 co-precipitate from mouse brain
      extract and from synaptosomal fractions, consistent with an endogenous
      interaction in neurons. Thus, we examined microtubule dynamics and synaptic
      density in primary cortical neurons. We find that depletion of NCAM, inhibition
      of the dynein-NCAM180 interaction, or dampening of microtubule dynamics with low
      dose nocodazole all result in significantly decreased in synaptic density. Based
      on these observations, we propose a working model for the role of dynein at the
      synapse, in which the anchoring of the motor to the cortex via binding to an
      adhesion molecule mediates the tethering of dynamic microtubule plus-ends to
      potentiate synaptic stabilization. 

PMID- 23960071
TI  - Metal switch-controlled myosin II from Dictyostelium discoideum supports closure
      of nucleotide pocket during ATP binding coupled to detachment from actin
      filaments.
AB  - G-proteins, kinesins, and myosins are hydrolases that utilize a common protein
      fold and divalent metal cofactor (typically Mg(2+)) to coordinate purine
      nucleotide hydrolysis. The nucleoside triphosphorylase activities of these
      enzymes are activated through allosteric communication between the nucleotide
      binding site and the activator/effector/polymer interface to convert the free
      energy of nucleotide hydrolysis into molecular switching (G-proteins) or force
      generation (kinesins and myosin). We have investigated the ATPase mechanisms of
      wild-type and the S237C mutant of non-muscle myosin II motor from Dictyostelium
      discoideum. The S237C substitution occurs in the conserved metal-interacting
      switch-1, and we show that this substitution modulates the actomyosin interaction
      based on the divalent metal present in solution. Surprisingly, S237C shows rapid
      basal steady-state Mg(2+)- or Mn(2+)-ATPase kinetics, but upon binding actin, its
      MgATPase is inhibited. This actin inhibition is relieved by Mn(2+), providing a
      direct and experimentally reversible linkage of switch-1 and the actin-binding
      cleft through the swapping of divalent metals in the reaction. Using pyrenyl
      labeled F-actin, we demonstrate that acto.S237C undergoes slow and weak MgATP
      binding, which limits the rate of steady-state catalysis. Mn(2+) rescues this
      effect to near wild-type activity. 2'(3')-O-(N-Methylanthraniloyl)-ADP release
      experiments show the need for switch-1 interaction with the metal cofactor for
      tight ADP binding. Our results are consistent with strong reciprocal coupling of
      nucleoside triphosphate and F-actin binding and provide additional evidence for
      the allosteric communication pathway between the nucleotide-binding site and the
      filament-binding region. 

PMID- 23960072
TI  - Decreasing tropomyosin phosphorylation rescues tropomyosin-induced familial
      hypertrophic cardiomyopathy.
AB  - Studies indicate that tropomyosin (Tm) phosphorylation status varies in different
      mouse models of cardiac disease. Investigation of basal and acute cardiac
      function utilizing a mouse model expressing an alpha-Tm protein that cannot be
      phosphorylated (S283A) shows a compensated hypertrophic phenotype with
      significant increases in SERCA2a expression and phosphorylation of phospholamban
      Ser-16 (Schulz, E. M., Correll, R. N., Sheikh, H. N., Lofrano-Alves, M. S.,
      Engel, P. L., Newman, G., Schultz Jel, J., Molkentin, J. D., Wolska, B. M.,
      Solaro, R. J., and Wieczorek, D. F. (2012) J. Biol. Chem. 287, 44478-44489). With
      these results, we hypothesized that decreasing alpha-Tm phosphorylation may be
      beneficial in the context of a chronic, intrinsic stressor. To test this
      hypothesis, we utilized the familial hypertrophic cardiomyopathy (FHC) alpha-Tm
      E180G model (Prabhakar, R., Boivin, G. P., Grupp, I. L., Hoit, B., Arteaga, G.,
      Solaro, R. J., and Wieczorek, D. F. (2001) J. Mol. Cell. Cardiol. 33, 1815-1828).
      These FHC hearts are characterized by increased heart:body weight ratios,
      fibrosis, increased myofilament Ca(2+) sensitivity, and contractile defects. The
      FHC mice die by 6-8 months of age. We generated mice expressing both the E180G
      and S283A mutations and found that the hypertrophic phenotype was rescued in the
      alpha-Tm E180G/S283A double mutant transgenic animals; these mice exhibited no
      signs of cardiac hypertrophy and displayed improved cardiac function. These
      double mutant transgenic hearts showed increased phosphorylation of phospholamban
      Ser-16 and Thr-17 compared with the alpha-Tm E180G mice. This is the first study
      to demonstrate that decreasing phosphorylation of tropomyosin can rescue a
      hypertrophic cardiomyopathic phenotype. 

PMID- 23960073
TI  - FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits
      tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas.
AB  - The p21-activated kinases (PAKs) are immediate downstream effectors of the
      Rac/Cdc42 small G-proteins and implicated in promoting tumorigenesis in various
      types of cancer including breast and lung carcinomas. Recent studies have
      established a requirement for the PAKs in the pathogenesis of Neurofibromatosis
      type 2 (NF2), a dominantly inherited cancer disorder caused by mutations at the
      NF2 gene locus. Merlin, the protein product of the NF2 gene, has been shown to
      negatively regulate signaling through the PAKs and the tumor suppressive
      functions of Merlin are mediated, at least in part, through inhibition of the
      PAKs. Knockdown of PAK1 and PAK2 expression, through RNAi-based approaches,
      impairs the proliferation of NF2-null schwannoma cells in culture and inhibits
      their ability to form tumors in vivo. These data implicate the PAKs as potential
      therapeutic targets. High-throughput screening of a library of small molecules
      combined with a structure-activity relationship approach resulted in the
      identification of FRAX597, a small-molecule pyridopyrimidinone, as a potent
      inhibitor of the group I PAKs. Crystallographic characterization of the
      FRAX597/PAK1 complex identifies a phenyl ring that traverses the gatekeeper
      residue and positions the thiazole in the back cavity of the ATP binding site, a
      site rarely targeted by kinase inhibitors. FRAX597 inhibits the proliferation of
      NF2-deficient schwannoma cells in culture and displayed potent anti-tumor
      activity in vivo, impairing schwannoma development in an orthotopic model of NF2.
      These studies identify a novel class of orally available ATP-competitive Group I
      PAK inhibitors with significant potential for the treatment of NF2 and other
      cancers. 

PMID- 23960074
TI  - Regulation of mammalian target of rapamycin complex 1 by Bcl-2 and Bcl-XL
      proteins.
AB  - Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell
      growth and metabolism. Its activity is controlled by various types of signals,
      including growth factors, nutrients, and stresses. In this study, we show that
      changes in expression levels of two antiapoptotic proteins, Bcl-2 and Bcl-XL,
      also affect mTORC1 signaling activity. In cells overexpressing Bcl-XL, mTORC1
      activity is increased and becomes less sensitive to growth factor or nutrient
      conditions. In contrast, reduction in expression levels of the two antiapoptotic
      proteins inhibits mTORC1 signaling activity. Our results suggest that the effect
      of Bcl-2 and Bcl-XL on mTORC1 is mediated by FKBP38, an inhibitor of mTORC1. The
      two proteins compete with mTORC1 for FKBP38 binding and hence alter mTORC1
      activity. This study reveals a novel cross-talk between Bcl-2/XL and mTORC1
      signaling, which is likely to contribute to cancer development. 

PMID- 23960075
TI  - JNK3 enzyme binding to arrestin-3 differentially affects the recruitment of
      upstream mitogen-activated protein (MAP) kinase kinases.
AB  - Arrestin-3 was previously shown to bind JNK3alpha2, MKK4, and ASK1. However, full
      JNK3alpha2 activation requires phosphorylation by both MKK4 and MKK7. Using
      purified proteins we show that arrestin-3 directly interacts with MKK7 and
      promotes JNK3alpha2 phosphorylation by both MKK4 and MKK7 in vitro as well as in
      intact cells. The binding of JNK3alpha2 promotes an arrestin-3 interaction with
      MKK4 while reducing its binding to MKK7. Interestingly, the arrestin-3
      concentration optimal for scaffolding the MKK7-JNK3alpha2 module is ~10-fold
      higher than for the MKK4-JNK3alpha2 module. The data provide a mechanistic basis
      for arrestin-3-dependent activation of JNK3alpha2. The opposite effects of
      JNK3alpha2 on arrestin-3 interactions with MKK4 and MKK7 is the first
      demonstration that the kinase components in mammalian MAPK cascades regulate each
      other's interactions with a scaffold protein. The results show how signaling
      outcomes can be affected by the relative expression of scaffolding proteins and
      components of signaling cascades that they assemble. 

PMID- 23960076
TI  - An androgen receptor-microrna-29a regulatory circuitry in mouse epididymis.
AB  - MicroRNAs are involved in a number of cellular processes; thus, their
      deregulation is usually apt to the occurrence of diverse diseases. Previous
      studies indicate that abnormally up-regulated miR-29a is associated with several
      diseases, such as human acute myeloid leukemia and diabetes; therefore, the
      proper level of miR-29a is critical for homeostasis. Herein, we observed that miR
      29a was repressed by androgen/androgen receptor signaling in mouse epididymis by
      targeting a conserved androgen response element located 8 kb upstream of miR
      29b1a loci. It is well known that multiple regulatory programs often form a
      complicated network. Here, we found that miR-29a reversibly suppressed androgen
      receptor and its target genes by targeting IGF1 and p53 pathways. miR-29b1a
      overexpressing transgenic mice displayed epididymis hypoplasia partially similar
      to the phenotype of those mice with an impaired androgen-androgen receptor signal
      system. Taken together, the results demonstrated that there is a regulatory
      circuitry between the androgen signaling pathway and miR-29a in mouse epididymis
      that may be vital for epididymal development and functions. 

PMID- 23960077
TI  - Structural and functional properties of the membranotropic HIV-1 glycoprotein
      gp41 loop region are modulated by its intrinsic hydrophobic core.
AB  - The gp41 disulfide loop region switches from a soluble state to a membrane-bound
      state during the human immunodeficiency virus type 1 (HIV-1) envelope-mediated
      membrane fusion process. The loop possesses a hydrophobic core at the center of
      the region with an unusual basic residue (Lys-601). Furthermore, two loop core
      mutations, K601A and L602A, are found to inhibit HIV-1 infectivity while keeping
      wild type-like levels of the envelope, implying that they exert an inhibitory
      effect on gp41 during the membrane fusion event. Here, we investigated the mode
      of action of these mutations on the loop region. We show that the K601A mutation,
      but not the L602A mutation, abolished the binding of a loop-specific monoclonal
      antibody to a loop domain peptide. Additionally, the K601A, but not the L602A,
      impaired disulfide bond formation in the peptides. This was correlated with
      changes in the circular dichroism spectrum imposed by the K601A mutation. In the
      membrane, however, the L602A, but not the K601A, reduced the lipid mixing ability
      of the loop peptides, which was correlated with decreased alpha-helical content
      of the L602A mutant. The results suggest that the Lys-601 residue provides a
      moderate hydrophobicity level within the gp41 loop core that contributes to the
      proper structure and function of the loop inside and outside the membrane.
      Because basic residues are found between the loop Cys residues of several
      lentiviral fusion proteins, the findings may contribute to understanding the
      fusion mechanism of other viruses as well. 

PMID- 23960078
TI  - Angiopoietin-like protein 4 inhibition of lipoprotein lipase: evidence for
      reversible complex formation.
AB  - Elevated triglycerides are associated with an increased risk of cardiovascular
      disease, and lipoprotein lipase (LPL) is the rate-limiting enzyme for the
      hydrolysis of triglycerides from circulating lipoproteins. The N-terminal domain
      of angiopoietin-like protein 4 (ANGPTL4) inhibits LPL activity. ANGPTL4 was
      previously described as an unfolding molecular chaperone of LPL that
      catalytically converts active LPL dimers into inactive monomers. Our studies show
      that ANGPTL4 is more accurately described as a reversible, noncompetitive
      inhibitor of LPL. We find that inhibited LPL is in a complex with ANGPTL4, and
      upon dissociation, LPL regains lipase activity. Furthermore, we have generated a
      variant of ANGPTL4 that is dependent on divalent cations for its ability to
      inhibit LPL. We show that LPL inactivation by this regulatable variant of ANGPTL4
      is fully reversible after treatment with a chelator. 

PMID- 23960079
TI  - The N-degradome of Escherichia coli: limited proteolysis in vivo generates a
      large pool of proteins bearing N-degrons.
AB  - The N-end rule is a conserved mechanism found in Gram-negative bacteria and
      eukaryotes for marking proteins to be degraded by ATP-dependent proteases.
      Specific N-terminal amino acids (N-degrons) are sufficient to target a protein to
      the degradation machinery. In Escherichia coli, the adaptor ClpS binds an N
      degron and delivers the protein to ClpAP for degradation. As ClpS recognizes N
      terminal Phe, Trp, Tyr, and Leu, which are not found at the N terminus of
      proteins translated and processed by the canonical pathway, proteins must be post
      translationally modified to expose an N-degron. One modification is catalyzed by
      Aat, an enzyme that adds leucine or phenylalanine to proteins with N-terminal
      lysine or arginine; however, such proteins are also not generated by the
      canonical protein synthesis pathway. Thus, the mechanisms producing N-degrons in
      proteins and the frequency of their occurrence largely remain a mystery. To
      address these issues, we used a ClpS affinity column to isolate interacting
      proteins from E. coli cell lysates under non-denaturing conditions. We identified
      more than 100 proteins that differentially bound to a column charged with wild
      type ClpS and eluted with a peptide bearing an N-degron. Thirty-two of 37
      determined N-terminal peptides had N-degrons. Most of the proteins were N
      terminally truncated by endoproteases or exopeptidases, and many were further
      modified by Aat. The identities of the proteins point to possible physiological
      roles for the N-end rule in cell division, translation, transcription, and DNA
      replication and reveal widespread proteolytic processing of cellular proteins to
      generate N-end rule substrates. 

PMID- 23960080
TI  - Mechanism for recognition of an unusual mycobacterial glycolipid by the
      macrophage receptor mincle.
AB  - Binding of the macrophage lectin mincle to trehalose dimycolate, a key glycolipid
      virulence factor on the surface of Mycobacterium tuberculosis and Mycobacterium
      bovis, initiates responses that can lead both to toxicity and to protection of
      these pathogens from destruction. Crystallographic structural analysis, site
      directed mutagenesis, and binding studies with glycolipid mimics have been used
      to define an extended binding site in the C-type carbohydrate recognition domain
      (CRD) of bovine mincle that encompasses both the headgroup and a portion of the
      attached acyl chains. One glucose residue of the trehalose Glcalpha1-1Glcalpha
      headgroup is liganded to a Ca(2+) in a manner common to many C-type CRDs, whereas
      the second glucose residue is accommodated in a novel secondary binding site. The
      additional contacts in the secondary site lead to a 36-fold higher affinity for
      trehalose compared with glucose. An adjacent hydrophobic groove, not seen in
      other C-type CRDs, provides a docking site for one of the acyl chains attached to
      the trehalose, which can be targeted with small molecule analogs of trehalose
      dimycolate that bind with 52-fold higher affinity than trehalose. The data
      demonstrate how mincle bridges between the surfaces of the macrophage and the
      mycobacterium and suggest the possibility of disrupting this interaction. In
      addition, the results may provide a basis for design of adjuvants that mimic the
      ability of mycobacteria to stimulate a response to immunization that can be
      employed in vaccine development. 

PMID- 23960081
TI  - Identification of ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) as a
      regulator of N-acetylglucosaminyltransferase GnT-IX (GnT-Vb).
AB  - Our previous studies on a beta1,6-N-acetylglucosaminyltransferase, GnT-IX (GnT
      Vb), a homolog of GnT-V, indicated that the enzyme has a broad GlcNAc transfer
      activity toward N-linked and O-mannosyl glycan core structures and that its brain
      specific gene expression is regulated by epigenetic histone modifications. In
      this study, we demonstrate the existence of an endogenous inhibitory factor for
      GnT-IX that functions as a key regulator for GnT-IX enzymatic activity in Neuro2a
      (N2a) cells. We purified this factor from N2a cells and found that it is
      identical to ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3), as
      evidenced by mass spectrometry and by the knockdown and overexpression of ENPP3
      in cultured cells. Kinetic analyses revealed that the mechanism responsible for
      the inhibition of GnT-IX caused by ENPP3 is the ENPP3-mediated hydrolysis of the
      nucleotide sugar donor substrate, UDP-GlcNAc, with the resulting generation of
      UMP, a potent and competitive inhibitor of GnT-IX. Indeed, ENPP3 knockdown cells
      had significantly increased levels of intracellular nucleotide sugars and
      displayed changes in the total cellular glycosylation profile. In addition to
      chaperones or other known regulators of glycosyltransferases, the ENPP3-mediated
      hydrolysis of nucleotide sugars would have widespread and significant impacts on
      glycosyltransferase activities and would be responsible for altering the total
      cellular glycosylation profile and modulating cellular functions. 

PMID- 23960082
TI  - Tyrosine phosphorylation on spleen tyrosine kinase (Syk) is differentially
      regulated in human and murine platelets by protein kinase C isoforms.
AB  - Protein kinase C (PKC) isoforms differentially regulate platelet functional
      responses downstream of glycoprotein VI (GPVI) signaling, but the role of PKCs
      regulating upstream effectors such as Syk is not known. We investigated the role
      of PKC on Syk tyrosine phosphorylation using the pan-PKC inhibitor GF109203X
      (GFX). GPVI-mediated phosphorylation on Syk Tyr-323, Tyr-352, and Tyr-525/526 was
      rapidly dephosphorylated, but GFX treatment inhibited this dephosphorylation on
      Tyr-525/526 in human platelets but not in wild type murine platelets. GFX
      treatment did not affect tyrosine phosphorylation on FcRgamma chain or Src family
      kinases. Phosphorylation of Lat Tyr-191 and PLCgamma2 Tyr-759 was also increased
      upon treatment with GFX. We evaluated whether secreted ADP is required for such
      dephosphorylation. Exogenous addition of ADP to GFX-treated platelets did not
      affect tyrosine phosphorylation on Syk. FcgammaRIIA- or CLEC-2-mediated Syk
      tyrosine phosphorylation was also potentiated with GFX in human platelets.
      Because potentiation of Syk phosphorylation is not observed in murine platelets,
      PKC-deficient mice cannot be used to identify the PKC isoform regulating Syk
      phosphorylation. We therefore used selective inhibitors of PKC isoforms. Only
      PKCbeta inhibition resulted in Syk hyperphosphorylation similar to that in
      platelets treated with GFX. This result indicates that PKCbeta is the isoform
      responsible for Syk negative regulation in human platelets. In conclusion, we
      have elucidated a novel pathway of Syk regulation by PKCbeta in human platelets. 

PMID- 23960083
TI  - Multiple ligands of von Willebrand factor-binding protein (vWbp) promote
      Staphylococcus aureus clot formation in human plasma.
AB  - Staphylococcus aureus secretes coagulase (Coa) and von Willebrand factor-binding
      protein (vWbp) to activate host prothrombin and form fibrin cables, thereby
      promoting the establishment of infectious lesions. The D1-D2 domains of Coa and
      vWbp associate with, and non-proteolytically activate prothrombin. Moreover, Coa
      encompasses C-terminal tandem repeats for binding to fibrinogen, whereas vWbp has
      been reported to associate with von Willebrand factor and fibrinogen. Here we
      used affinity chromatography with non-catalytic Coa and vWbp to identify the
      ligands for these virulence factors in human plasma. vWbp bound to prothrombin,
      fibrinogen, fibronectin, and factor XIII, whereas Coa co-purified with
      prothrombin and fibrinogen. vWbp association with fibrinogen and factor XIII, but
      not fibronectin, required prothrombin and triggered the non-proteolytic
      activation of FXIII in vitro. Staphylococcus aureus coagulation of human plasma
      was associated with the recruitment of prothrombin, FXIII, and fibronectin as
      well as the formation of cross-linked fibrin. FXIII activity in staphylococcal
      clots could be attributed to thrombin-dependent proteolytic activation as well as
      vWbp-mediated non-proteolytic activation of FXIII zymogen. 

PMID- 23960085
TI  - New oral anticoagulants in heart failure.

PMID- 23960086
TI  - Haemodilution is a mechanism of anaemia in patients with heart failure: reply.

PMID- 23960087
TI  - Involvement of OpcR, a GbsR-type transcriptional regulator, in negative
      regulation of two evolutionarily closely related choline uptake genes in Bacillus
      subtilis.
AB  - The osmoprotectant glycine betaine can be generated intracellularly from
      conversion of the exogenous precursor choline by enzymes encoded by the gbsAB
      operon in Bacillus subtilis. Uptake of choline from outside B. subtilis cells is
      mediated through two evolutionarily closely related ATP-binding cassette
      transporters, OpuB and OpuC. Expression of the opuB operon and of the opuC operon
      is known to be osmoinducible. Here, we show that choline exerts a suppressive
      effect on opuC expression during normal growth and under osmotic stress. In the
      absence of the choline-responsive repressor GbsR, opuB expression is also
      suppressed by choline. We also report that a gene (formerly yvbF, now designated
      opcR) located immediately upstream of the opuC operon negatively regulates
      transcription of the opuC operon and, in the absence of GbsR, also that of the
      opuB operon. An inverted repeat (TTGTAAA-N8-TTTACAA) that overlaps with the -35
      hexamer of the promoters of both operons has been identified as the OpcR
      operator. OpcR belongs to the GbsR-type transcriptional regulators. Its
      orthologues with unknown function are present in some other Bacillus species.
      Moreover, deletion analyses revealed that a region located further upstream of
      the promoters of the opuB operon and the opuC operon is critical for expression
      of both operons during normal growth and under osmotic stress. Osmotic induction
      of these two operons appears not to be OpcR mediated. OpcR is not a choline
      responsive repressor. The possible biological role of OpcR is discussed. 

PMID- 23960084
TI  - Autophagy deficiency by hepatic FIP200 deletion uncouples steatosis from liver
      injury in NAFLD.
AB  - Nonalcoholic fatty liver disease is a metabolic disorder commonly associated with
      obesity. A subset of nonalcoholic fatty liver disease patients further develops
      nonalcoholic steatohepatitis that is characterized by chronic liver injury,
      inflammation, and fibrosis. Recent work has implicated the autophagy pathway in
      the mobilization and oxidation of triglycerides from lipid droplets. However,
      whether impaired autophagy in hepatocytes drives excess fat accumulation in the
      liver remains controversial. In addition, the role of autophagy in protecting the
      liver from gut endotoxin-induced injury has not been elucidated. Here we
      generated mice with liver-specific autophagy deficiency by the conditional
      deletion of focal adhesion kinase family kinase-interacting protein of 200 kDa
      (also called Rb1cc1), a core subunit of the mammalian autophagy related 1
      complex. To our surprise, mice lacking FIP200 in hepatocytes were protected from
      starvation- and high-fat diet-induced fat accumulation in the liver and had
      decreased expression of genes involved in lipid metabolism. Activation of the de
      novo lipogenic program by liver X receptor was impaired in FIP200-deficient
      livers. Furthermore, liver autophagy was stimulated by exposure to low doses of
      lipopolysaccharides and its deficiency-sensitized mice to endotoxin-induced liver
      injury. Together these studies demonstrate that hepatocyte-specific autophagy
      deficiency per se does not exacerbate hepatic steatosis. Instead, autophagy may
      play a protective role in the liver after exposure to gut-derived endotoxins and
      its blockade may accelerate nonalcoholic steatohepatitis progression. 

PMID- 23960088
TI  - Selective atrial profibrotic signalling in mice and man.

PMID- 23960090
TI  - Do we need more or better electrophysiology centres?

PMID- 23960091
TI  - Reduced forced expiratory volume is associated with increased incidence of atrial
      fibrillation: the Malmo Preventive Project.
AB  - AIMS: Reduced forced expiratory volume in one second (FEV1) and forced vital
      capacity (FVC) have been associated with increased incidence of cardiovascular
      diseases. However, whether reduced lung function is also a risk factor for
      incidence of atrial fibrillation (AF) is still unclear. We aimed to determine
      whether lung function predicted AF in the Malmo Preventive Project, a large
      population-based cohort with a long follow-up. METHODS AND RESULTS: The study
      population consisted of 7674 women and 21 070 men, mean age 44.6 years. The
      cohort was followed on average for 24.8 years, during which time 2669 patients
      were hospitalized due to AF. The incidence of AF in relationship to quartiles of
      FEV1 and FVC and per litre decrease at baseline was determined using a Cox
      proportional hazards model adjusted for age, height, weight, current smoking
      status, systolic blood pressure, erythrocyte sedimentation rate, and fasting
      blood glucose. Forced expiratory volume in one second was inversely related to
      incidence of AF (per litre reduction in FEV1) hazard ratio (HR): 1.39 [95%
      confidence interval (CI): 1.16-1.68; P = 0.001] for women, and HR: 1.20 (95% CI:
      1.13-1.29; P < 0.0001) for men. Forced vital capacity was also inversely related
      to incidence of AF (per litre reduction in FVC) HR: 1.20 (95% CI: 1.03-1.41; P =
      0.020) for women, and HR: 1.08 (95% CI: 1.02-1.14; P = 0.01) for men. This
      relationship was consistent in non-smokers as well as smokers, and among
      individuals younger than the median age of 45.8 years or normotensive subjects.
      CONCLUSION: Impaired lung function is an independent predictor of AF. This may
      explain some risk of AF that is currently unaccounted for.

PMID- 23960092
TI  - 'Green light': watch it twice...

PMID- 23960093
TI  - Development of healthcare quality indicators for rheumatoid arthritis in Europe:
      the eumusc.net project.
AB  - BACKGROUND: Eumusc.net (http://www.eumusc.net) is a European project supported by
      the EU and European League Against Rheumatism to improve musculoskeletal care in
      Europe. OBJECTIVE: To develop patient-centred healthcare quality indicators
      (HCQIs) for healthcare provision for rheumatoid arthritis (RA) patients. METHODS:
      Based on a systematic literature search, existing HCQIs for RA were identified
      and their contents analysed and categorised referring to a list of 16 standards
      of care developed within the eumusc.net. An international expert panel comprising
      14 healthcare providers and two patient representatives added topics and during
      repeated Delphi processes by email ranked the topics and rephrased suggested
      HCQIs with the preliminary set being established during a second expert group
      meeting. After an audit process by rheumatology units (including academic
      centres) in six countries (The Netherlands, Norway, Romania, Italy, Austria and
      Sweden), a final version of the HCQIs was established. RESULTS: 56 possible
      topics for HCQIs were processed resulting in a final set of HCQIs for RA (n=14)
      including two for structure (patient information and calculation of composite
      scores), 11 for process (eg, access to care, assessments, and pharmacological and
      non-pharmacological treatments) and one for outcome (effect of treatment on
      disease activity). They included definitions to be used in clinical practice and
      also by patients. Further, the numerators and the denominators for each HCQI were
      defined. CONCLUSIONS: A set of 14 patient-centred HCQIs for RA was developed to
      be used in quality improvement and bench marking in countries across Europe.

PMID- 23960094
TI  - Contribution of ATM and ATR to the resistance of glioblastoma and malignant
      melanoma cells to the methylating anticancer drug temozolomide.
AB  - The major cytotoxic DNA adduct induced by temozolomide and other methylating
      agents used in malignant glioma and metastasized melanoma therapy is O(6)
      methylguanine (O(6)-MeG). This primary DNA damage is converted by mismatch repair
      into secondary lesions, which block replication and in turn induce DNA double
      strand breaks that trigger the DNA damage response (DDR). Key upstream players in
      the DDR are the phosphoinositide 3-kinases ataxia telangiectasia mutated (ATM)
      and ataxia telangiectasia and Rad3 related (ATR). Here, we addressed the question
      of the importance of ATM and ATR in the cell death response following
      temozolomide. We show that (i) ATM- and ATR-mutated cells are hypersensitive to
      temozolomide, (ii) O(6)-MeG triggers ATM and ATR activation, (iii) knockdown of
      ATM and ATR enhances cell kill in gliobalstoma and malignant melanoma cells with
      a stronger and significant effect in ATR knockdown cells, (iv) ATR, but not ATM,
      knockdown abolished phosphorylation of H2AX, CHK1, and CHK2 in glioma cells, and
      (v) temozolomide-induced cell death was more prominently enhanced by
      pharmacologic inhibition of CHK1 compared with CHK2. The data suggest that ATM
      and, even better, ATR inhibition is a useful strategy in sensitizing cancer cells
      to temozolomide and presumably also other anticancer drugs.

PMID- 23960095
TI  - Sorafenib overcomes irinotecan resistance in colorectal cancer by inhibiting the
      ABCG2 drug-efflux pump.
AB  - Despite recent advances in the treatment of colorectal cancer (CRC), tumor
      resistance is a frequent cause of chemotherapy failure. Therefore, new treatment
      options are needed to improve survival of patients with irinotecan-refractory
      CRCs, particularly those bearing KRAS mutations that preclude the use of anti
      EGFR therapies. In this study, we investigated whether sorafenib could reverse
      irinotecan resistance, thereby enhancing the therapeutic efficacy of routinely
      used irinotecan-based chemotherapy. We used both in vitro (the HCT116, SW48,
      SW620, and HT29 colon adenocarcinoma cell lines and four SN-38-resistant HCT-116
      and SW48 clones) and in vivo models (nude mice xenografted with SN-38-resistant
      HCT116 cells) to test the efficacy of sorafenib alone or in combination with
      irinotecan or its active metabolite, SN-38. We have shown that sorafenib improved
      the antitumoral activity of irinotecan in vitro, in both parental and SN-38
      resistant colon adenocarcinoma cell lines independently of their KRAS status, as
      well as in vivo, in xenografted mice. By inhibiting the drug-efflux pump ABCG2,
      sorafenib favors irinotecan intracellular accumulation and enhances its toxicity.
      Moreover, we found that sorafenib improved the efficacy of irinotecan by
      inhibiting the irinotecan-mediated p38 and ERK activation. In conclusion, our
      results show that sorafenib can suppress resistance to irinotecan and suggest
      that sorafenib could be used to overcome resistance to irinotecan-based
      chemotherapies in CRC, particularly in KRAS-mutated tumors.

PMID- 23960096
TI  - Berbamine inhibits the growth of liver cancer cells and cancer-initiating cells
      by targeting Ca2+/calmodulin-dependent protein kinase II.
AB  - Liver cancer is the third leading cause of cancer deaths worldwide but no
      effective treatment toward liver cancer is available so far. Therefore, there is
      an unmet medical need to identify novel therapies to efficiently treat liver
      cancer and improve the prognosis of this disease. Here, we report that berbamine
      and one of its derivatives, bbd24, potently suppressed liver cancer cell
      proliferation and induced cancer cell death by targeting Ca(2+)/calmodulin
      dependent protein kinase II (CAMKII). Furthermore, berbamine inhibited the in
      vivo tumorigenicity of liver cancer cells in NOD/SCID mice and downregulated the
      self-renewal abilities of liver cancer-initiating cells. Chemical inhibition or
      short hairpin RNA-mediated knockdown of CAMKII recapitulated the effects of
      berbamine, whereas overexpression of CAMKII promoted cancer cell proliferation
      and increased the resistance of liver cancer cells to berbamine treatments.
      Western blot analyses of human liver cancer specimens showed that CAMKII was
      hyperphosphorylated in liver tumors compared with the paired peritumor tissues,
      which supports a role of CAMKII in promoting human liver cancer progression and
      the potential clinical use of berbamine for liver cancer therapies. Our data
      suggest that berbamine and its derivatives are promising agents to suppress liver
      cancer growth by targeting CAMKII. Mol Cancer Ther; 12(10); 2067-77. (c)2013
      AACR. 

PMID- 23960097
TI  - Antibiotics and their effects: what do patients know and what is their source of
      information?
AB  - BACKGROUND: The Eurobarometer 2010 report on antimicrobial resistance included a
      survey on the knowledge of Europeans about antibiotics. Austria was ranked at the
      bottom of the EU27 countries. Based on these alarming results, it was the aim of
      this study to analyse demographic characteristics of patients and general
      practitioners in Austria to assess possible predictors for this outcome as well
      as to assess the main source of information related to antibiotics. METHODS: This
      cross-sectional study was conducted within the context of the European APRES
      project. An additional 12-item questionnaire was developed asking for the
      knowledge about antibiotics, demographic data and the source of information.
      Statistical analyses included subgroup analyses and linear mixed regression
      models. RESULTS: Overall, 3280 questionnaires were analysed. On average, 2.78
      (standard deviation 1.69) out of the six knowledge questions were answered
      correctly. The main predictors for a low knowledge score were low educational
      level, age, speaking another language than German and male sex. In all, 55.6% of
      the participants marked the general practitioner as main source of information.
      However, the source was less important for the knowledge score than their highest
      educational level. CONCLUSION: The Eurobarometer report result for Austrians
      could be confirmed and important associations and predictors could be identified:
      a multifaceted and evidence informed strategy is needed to improve the situation,
      which should both focus on target-group-specific interventions at the individual
      level to increase the knowledge of people with the highest needs as well as on
      strengthening the primary health care and educational sector at the system level.

PMID- 23960098
TI  - A case of recurrent toxin-mediated perineal erythema.

PMID- 23960099
TI  - Leveraging gene co-expression networks to pinpoint the regulation of complex
      traits and disease, with a focus on cardiovascular traits.
AB  - Over the past decade, the number of genome-scale transcriptional datasets in
      publicly available databases has climbed to nearly one million, providing an
      unprecedented opportunity for extensive analyses of gene co-expression networks.
      In systems-genetic studies of complex diseases researchers increasingly focus on
      groups of highly interconnected genes within complex transcriptional networks
      (referred to as clusters, modules or subnetworks) to uncover specific molecular
      processes that can inform functional disease mechanisms and pathological
      pathways. Here, we outline the basic paradigms underlying gene co-expression
      network analysis and critically review the most commonly used computational
      methods. Finally, we discuss specific applications of network-based approaches to
      the study of cardiovascular traits, which highlight the power of integrated
      analyses of networks, genetic and gene-regulation data to elucidate the complex
      mechanisms underlying cardiovascular disease. 

PMID- 23960101
TI  - Perioperative medicine.

PMID- 23960102
TI  - What to do when your brain turns blue? Considerations during aortic arch surgery.

PMID- 23960100
TI  - Caged naloxone reveals opioid signaling deactivation kinetics.
AB  - The spatiotemporal dynamics of opioid signaling in the brain remain poorly
      defined. Photoactivatable opioid ligands provide a means to quantitatively
      measure these dynamics and their underlying mechanisms in brain tissue. Although
      activation kinetics can be assessed using caged agonists, deactivation kinetics
      are obscured by slow clearance of agonist in tissue. To reveal deactivation
      kinetics of opioid signaling we developed a caged competitive antagonist that can
      be quickly photoreleased in sufficient concentrations to render agonist
      dissociation effectively irreversible. Carboxynitroveratryl-naloxone (CNV-NLX), a
      caged analog of the competitive opioid antagonist NLX, was readily synthesized
      from commercially available NLX in good yield and found to be devoid of
      antagonist activity at heterologously expressed opioid receptors. Photolysis in
      slices of rat locus coeruleus produced a rapid inhibition of the ionic currents
      evoked by multiple agonists of the MU-opioid receptor (MOR), but not of alpha
      adrenergic receptors, which activate the same pool of ion channels. Using the
      high-affinity peptide agonist dermorphin, we established conditions under which
      light-driven deactivation rates are independent of agonist concentration and thus
      intrinsic to the agonist-receptor complex. Under these conditions, some MOR
      agonists yielded deactivation rates that are limited by G protein signaling,
      whereas others appeared limited by agonist dissociation. Therefore, the choice of
      agonist determines which feature of receptor signaling is unmasked by CNV-NLX
      photolysis. 

PMID- 23960104
TI  - Theory-based interventions to reduce prescription of antibiotics--a randomized
      controlled trial in Sweden.
AB  - BACKGROUND: Upper respiratory tract infections (URTIs) are the most common reason
      for consulting a GP and for receiving an antibiotic prescription, although
      evidence shows poor benefit but rather increasing antibiotic resistance.
      Interventions addressing physicians have to take into consideration the
      complexity of prescribing behaviour. OBJECTIVE: To study whether interventions
      based on behavioural theories can reduce the prescribing of antibiotics against
      URTIs in primary care. Setting and subjects. GPs at 19 public primary health care
      centres in southern Sweden. METHODS: We performed a randomized controlled study
      using two behavioural theory-based interventions, the persuasive communication
      intervention (PCI) and the graded task intervention (GTI), which emerged from
      social cognitive theory and operant learning theory. GPs were randomized to a
      control group or one of two intervention groups (PCI and GTI). MAIN OUTCOME
      MEASURES: Changes in the rate of prescription of antibiotics against URTIs in
      primary care patients of all ages and in patients aged 0-6 years. RESULTS: No
      significant differences were seen in the prescription rates before and after the
      interventions when patients of all ages were analysed together. However, for
      patients aged 0-6 years, there was a significant lower prescription rate in the
      PCI group (P = 0.037), but not the GTI group, after intervention. CONCLUSION:
      Theory-based interventions have limited impact on reducing the prescription of
      antibiotics against URTIs in primary care. Future studies are needed to draw firm
      conclusions about their effects.

PMID- 23960105
TI  - Application of microarray analysis of foodborne Salmonella in poultry production:
      a review.
AB  - Salmonellosis in the United States is one of the most costly foodborne diseases.
      Given that Salmonella can originate from a wide variety of environments,
      reduction of this organism at all stages of poultry production is critical.
      Salmonella species can encounter various environmental stress conditions that can
      dramatically influence their survival and virulence. Previous knowledge of
      Salmonella species genomic regulation of metabolism and physiology in relation to
      poultry is based on limited information of a few well-characterized genes.
      Consequently, although there is some information about environmental signals that
      control Salmonella growth and pathogenesis, much still remains unknown.
      Advancements in DNA sequencing technologies revolutionized the way bacteria were
      studied and molecular tools such as microarrays have subsequently been used for
      comprehensive transcriptomic analysis of Salmonella. With microarray analysis,
      the expression levels of each single gene in the Salmonella genome can be
      directly assessed and previously unknown genetic systems that are required for
      Salmonella growth and survival in the poultry production cycle can be elucidated.
      This represents an opportunity for development of novel approaches for limiting
      Salmonella establishment in all phases of poultry production. In this review,
      recent advances in transcriptome-microarray technologies that are facilitating a
      better understanding of Salmonella biology in poultry production and processing
      are discussed. 

PMID- 23960106
TI  - Correlation between broiler lameness and anatomical measurements of bone using
      radiographical projections with assessments of consistency across and within
      radiographs.
AB  - Lameness represents a major welfare and production issue in the poultry industry
      with a recent survey estimating 27% of birds lame and 3% unable to walk by 40 d
      of age. A variety of factors may induce lameness and are typically grouped into 2
      broad classes on the basis of being infectious or skeletal in nature with the
      latter accounting for the majority of cases. The current work sought to build
      upon a large body of literature assessing the anatomical properties of bone in
      lame birds. Our specific objectives sought to identify relationships between
      relevant anatomical properties of the tibia and metatarsus using digital
      quantification from radiographs of legs and a measure of walking difficulty.
      Resulting output was statistically analyzed to assess 1) observer reliability for
      consistency in placing the leg during the radiograph procedure and quantification
      of the various measures within a radiograph, 2) the relationship between the
      various measurements of anatomical bone properties and sex, bird mass, and gait
      score, and 3) the relationship between each measurement and leg symmetry. Our
      anatomical bone measures were found to be reliable (intra-rater and test-retest
      reliabilities < 0.75) within radiograph for all measures and 8 of the 10 measures
      across radiographs. Several measures of bone properties in the tibia correlated
      to difficulty walking as measured by gait score (P < 0.05), indicating greater
      angulations with increasing lameness. Of the measures that manifested a gait
      score * bird mass interaction, heavier birds appeared to exhibit less angulation
      with increasing difficulty walking with lighter birds the opposite. These
      interactions suggest possibilities for influencing effects of activity or feed
      intake on bone mineralization with the bone angulation observed. Our efforts
      agree with that of others and indicate that angulation of the tibia may be
      related to lameness, though subsequent efforts involving comprehensive measures
      of bird activity, growth rates, and internal bone structure will be needed if the
      validity of the measures are to be accepted. 

PMID- 23960107
TI  - Fear, stress, and feather pecking in commercial white and brown laying hen parent
      stock flocks and their relationships with production parameters.
AB  - Little is known about the relationship between welfare traits and production in
      laying hen parent stock (PS). In commercial laying hens and pure lines, it is
      known that aspects associated with reduced welfare such as high fear, stress, and
      feather pecking can have negative effects on production. Because PS hens are
      housed under different conditions than commercial laying hens, the relationship
      between welfare traits and production may differ. We therefore studied the fear
      response to a stationary person (SP) and novel object (NO), basal plasma
      corticosterone (CORT) and whole-blood serotonin levels (5-HT), and feather damage
      as a proxy for feather pecking in 10 Dekalb White (DW) and 10 ISA Brown (ISA)
      commercial PS flocks and related these to production data. Because the
      relationship between welfare traits and production may differ by genetic origin
      and group size, we also assessed genotype and group size effects. Dekalb White
      birds were more fearful of a SP, and had more feather damage and lower 5-HT
      levels than ISA birds. Genotypes did not differ in CORT. A large group size (n >
      5,000) was associated with low feed intake and better feed conversion for ISA
      flocks. For DW flocks, high fear of the NO was associated with low BW, low egg
      weight, and low feed intake. For ISA flocks, high fear of the SP was associated
      with high mortality. For both lines, high CORT was related to low egg weight.
      This is the first study to associate levels of fear and CORT to production in
      commercial PS flocks. Management of PS flocks should take into account breed
      differences, group size effects, and effects of human-bird interactions. Further
      research is needed to determine the effects of fear, CORT, 5-HT, and feather
      damage in commercial PS flocks on the development of their offspring. 

PMID- 23960108
TI  - Pedigree and genomic analyses of feed consumption and residual feed intake in
      laying hens.
AB  - Efficiency of production is increasingly important with the current escalation of
      feed costs and demands to minimize the environmental footprint. The objectives of
      this study were 1) to estimate heritabilities for daily feed consumption and
      residual feed intake and their genetic correlations with production and egg
      quality traits; 2) to evaluate accuracies of estimated breeding values from
      pedigree- and marker-based prediction models; and 3) to localize genomic regions
      associated with feed efficiency in a brown egg layer line. Individual feed intake
      data collected over 2-wk trial periods were available for approximately 6,000
      birds from 8 generations. Genetic parameters were estimated with a multitrait
      animal model; methods BayesB and BayesCpi were used to estimate marker effects
      and find genomic regions associated with feed efficiency. Using pedigree
      information, feed efficiency was found to be moderately heritable (h(2) = 0.46
      for daily feed consumption and 0.47 for residual feed intake). Hens that consumed
      more feed and had greater residual feed intake (lower efficiency) had a genetic
      tendency to lay slightly more eggs with greater yolk weights and albumen heights.
      Regions on chromosomes 1, 2, 4, 7, 13, and Z were found to be associated with
      feed intake and efficiency. The accuracy from genomic prediction was higher and
      more persistent (better maintained across generations) than that from pedigree
      based prediction. These results indicate that genomic selection can be used to
      improve feed efficiency in layers. 

PMID- 23960109
TI  - Higher precision level at individual laying performance tests in noncage housing
      systems.
AB  - With the Weihenstephan funnel nest box, 12 laying hen flocks were tested for
      their individual laying performance, egg quality, and nesting behavior in a
      noncage environment. During the whole observation period of 8 yr, a transponder
      based data recording system was continuously improved and resulted in a recording
      accuracy of 97%. At peak production, heritabilities for the number of eggs laid
      are in some flocks higher than expected. With improved data accuracy,
      heritability estimates on individual egg weights are more stable. Heritabilities
      for nesting behavior traits range between a low to moderate level, providing very
      useful information for laying hen selection to help improve traits that cannot be
      recorded in cages. Over the years, the benefits of the Weihenstephan funnel nest
      box for laying hen breeders have grown. This is due to higher data recording
      accuracies and extended testing capacities, which result in more reliable genetic
      parameters. 

PMID- 23960110
TI  - Genetic parameters and principal component analysis for egg production from White
      Leghorn hens.
AB  - The objectives of this study were to estimate genetic parameters for accumulated
      egg production over 3-wk periods and for total egg production over 54 wk of egg
      laying, and using principal component analysis (PCA), to explore the
      relationships among the breeding values of these traits to identify the possible
      genetic relationships present among them and hence to observe which of them could
      be used as selection criteria for improving egg production. Egg production was
      measured among 1,512 females of a line of White Leghorn laying hens. The traits
      analyzed were the number of eggs produced over partial periods of 3 wk, thus
      totaling 18 partial periods (P1 to P18), and the total number of eggs produced
      over the period between the 17 and 70 wk of age (PTOT), thus totaling 54 wk of
      egg production. Estimates of genetic parameters were obtained by means of the
      restricted maximum likelihood method, using 2-trait animal models. The PCA was
      done using the breeding values of partial and total egg production. The
      heritability estimates ranged from 0.05 +/- 0.03 (P1 and P8) to 0.27 +/- 0.06
      (P4) in the 2-trait analysis. The genetic correlations between PTOT and partial
      periods ranged from 0.19 +/- 0.31 (P1) to 1.00 +/- 0.05 (P10, P11, and P12).
      Despite the high genetic correlation, selection of birds based on P10, P11, and
      P12 did not result in an increase in PTOT because of the low heritability
      estimates for these periods (0.06 +/- 0.03, 0.12 +/- 0.04, and 0.10 +/- 0.04,
      respectively). The PCA showed that egg production can be divided genetically into
      4 periods, and that P1 and P2 are independent and have little genetic association
      with the other periods. 

PMID- 23960111
TI  - Altered pro-inflammatory cytokine mRNA levels in chickens infected with
      infectious bronchitis virus.
AB  - Infectious bronchitis virus (IBV) replicates primarily in the respiratory tract
      and grows in various organs in chickens, with or without pathological effects.
      The diversity of this virus has been verified by sequence analysis of the S1
      glycoprotein gene, but this method must be supplemented with further analysis for
      characterization of the agent. To increase our understanding of the pathogenesis
      of the disease caused by this virus, we investigated the response of chickens to
      2 IBV with different genotypes, KIIa and ChVI. The clinical signs induced by the
      viruses were observed. In addition, the mRNA levels of the pro-inflammatory
      cytokines, IL-6, IL-1beta, and lipopolysaccharide-induced tumor necrosis factor
      alpha factor and the serum levels of alpha1-acid glycoprotein, which is a major
      acute phase protein, were measured. The KIIa genotype (Kr/ADL110002/2011) induced
      clinical signs accompanied by the excessive production of pro-inflammatory
      cytokines and a higher viral load. In chickens infected with this isolate,
      simultaneous peaks in the viral copy number and cytokine production were observed
      at 7 dpi in the trachea and 9 d postinoculation in the kidney. On the other hand,
      the chickens infected with the ChVI genotype (Kr/ADL120003/2012) did not show a
      response other than a mild upregulation of cytokines at 1 d postinoculation,
      which appears to indicate the invasion of the virus. In summary, we confirmed a
      differential innate response following infection with distinct IBV. We
      hypothesize that an excessive innate response contributes to the scale of the
      pathophysiologic effect in chickens. 

PMID- 23960112
TI  - Performance, histomorphology, and toll-like receptor, chemokine, and cytokine
      profile locally and systemically in broiler chickens fed diets supplemented with
      yeast-derived macromolecules.
AB  - The turnover of intestinal epithelial cells is a dynamic process that includes
      adequate cell proliferation and maturation in the presence of microbiota and
      migration and seeding of immune cells in early gut development in chickens. We
      studied the effect of yeast-derived macromolecules (YDM) on performance, gut
      health, and immune system gene expression in the intestine of broiler chickens.
      One thousand eighty 1-d-old birds, with 60 birds per pen and 6 pens per
      treatment, were randomly assigned to 3 treatment diets; a diet containing
      monensin (control), control diet supplemented with bacitracin methylene
      disalycylate (BMD), and BMD diet supplemented with YDM. Feed intake, BW,
      mortality, ileum histomorphology, and gene expression of Toll-like receptors
      (TLR2b, TLR4, and TLR21), cytokines [interferon (IFN)-gamma, IFN-beta, IL-12p35,
      IL-1beta, IL-6, IL-10, IL-8, IL-2, IL-4, and transforming growth factor (TGF)
      beta4], and cluster of differentiation (CD)40 in the ileum, cecal tonsil, bursa
      of Fabricius, and spleen were assessed. No significant overall difference in
      performance in terms of feed intake, BW gain, and G:F was observed among
      treatments (P > 0.05). The YDM diet resulted in significantly higher villi height
      and villi height:crypt depth ratio compared with BMD and control diets (P <
      0.05). A significantly lower mortality was observed in the YDM treatment compared
      with both control and BMD treatments. Compared with the control, gene expression
      analysis in YDM treatment showed no major change in response in the ileum,
      whereas higher CD40, IFN-beta, IL-beta, IL-6, TGF-beta4, IL-2, and IL-4 in the
      cecal tonsil; TLR2b, TLR4, TLR21, and TGF-beta4 in the bursa of Fabricius; and
      TLR4, IL-12p35, IFN-gamma, TGF-beta4, and IL-4 in the spleen was observed (P <
      0.05). In conclusion, supplementation of YDM supports pro- and anti-inflammatory
      cytokine production via T helper type 1 and 2 (Th1 and Th2) cell-associated
      pathways both locally and systemically with a stronger additive effect in the
      cecal tonsil in the presence of BMD in the diet of chickens. 

PMID- 23960113
TI  - Susceptibility of 4 commercial broiler crosses to lameness attributable to
      bacterial chondronecrosis with osteomyelitis.
AB  - Growing broilers on wire flooring provides an excellent experimental model for
      exposing susceptibility to lameness attributable to bacterial chondronecrosis
      with osteomyelitis (BCO). Two independent experiments (E1, E2) were designed to
      compare the susceptibilities of broilers from 4 commercial crosses (W, X, Y, and
      Z). The standard crosses (W and Y) grow rapidly at an early age, whereas high
      yield crosses (X and Z) initially tend to grow more slowly. Chicks were obtained
      from a commercial hatchery for E1, or were hatched at the University of Arkansas
      Poultry Research Hatchery for E2. Males and females were reared together (E1; n =
      360/cross) or separately (E2; n = 390/cross) in 3 * 3 m pens on litter or wire
      flooring (wire). Necropsies revealed lesions that were pathognomonic for BCO in
      >=94% of the birds that became lame. The SigmaStat Z-test was used to compare
      cumulative lameness incidences at 8 wk of age. For birds reared on litter,
      lameness incidences were low and did not differ between crosses or sexes (range:
      2.2 to 4.6%; P >= 0.6). When males were reared on wire, their lameness incidences
      (by cross) were E1 = 52% for W(b); 42% for X(c); 69% for Y(a), and 44% for Z(bc);
      E2 = 31% for W(b); 19% for X(c); 49% for Y(a); and 25% for Z(bc). For females
      reared on wire, the lameness incidences were E1 = 40% for W(b), 30% for X(c), 49%
      for Y(a), and 28% for Z(c); E2 = 16% for W; 15% for X; 16% for Y; and 15% for Z
      (ns). Accordingly, the hierarchical ranking for BCO susceptibility by broiler
      cross was X <= Z <= W < Y for males in E1 and E2, for females in E1, and for
      males and females pooled in E1 and E2. Standard broiler crosses developed higher
      incidences of lameness than high-yield crosses, implicating an association
      between rapid early growth and susceptibility to BCO. Rearing the females
      separately on wire in E2 led to uniformly low incidences of BCO, regardless of
      cross. Stress-mediated immunosuppression contributes to the pathogenesis of BCO;
      perhaps female broilers experience less social or competitive stress when reared
      separately from their male hatch mates. 

PMID- 23960114
TI  - Detection of resistance phenotype and genotype of avian Escherichia coli in Hebei
      Province.
AB  - We investigated the resistance of avian Escherichia coli to commonly used
      clinical antibiotics in Hebei Province. It is of significance to reveal the
      extent and mechanism of drug resistance, as well as to prevent and control
      colibacillosis. We investigated the resistance of 132 E. coli isolates to 5 kinds
      of antibiotics (including beta-lactams, aminoglycosides, tetracyclines,
      sulfonamides, and chloramphenicol) using the Kirby-Bauer drug susceptibility
      test, and resistance genes were detected by PCR. The results showed that the E.
      coli had a higher resistance rate to ampicillin, cephalotin, gentamicin,
      streptomycin, tetracycline, doxycycline, sulfamethoxazole trimethoprim,
      sulfamonomethoxine, and florfenicol, but it had higher sensitive rate to
      cefepime, imipenem, spectinomycin, and minocycline. Of the resistance genes, the
      TEM, aac(3)-IIa, tetA, Sul1, Sul2, and forl had higher positive rates. Therefore,
      drug resistance of avian E. coli in Hebei Province is very serious. The
      resistance mechanisms may include structure changes of the target enzyme mediated
      by multiresistance genes, and resulting in reduced affinity and increased efflux
      of antibiotics. 

PMID- 23960115
TI  - Decay of maternal antibodies in broiler chickens.
AB  - The objective of this study was to determine the decay rate of maternal
      antibodies against major broiler chicken pathogens. A total of 30 one-day-old
      broiler chicks were obtained from a commercial hatchery and reared in isolation.
      These chicks were retrieved from a parent flock that received a routine
      vaccination program. Chicks were bled at hatch and sequentially thereafter every
      5 d through 30 d of age. Maternal antibody titers were measured by ELISA for
      avian encephalomyelitis (AEV), avian influenza virus (AIV), chicken anemia virus
      (CAV), infectious bursal disease virus (IBDV), infectious bronchitis virus (IBV),
      infectious laryngotracheitis virus (ILTV), Mycoplasma gallisepticum (MG),
      Mycoplasma synoviae (MS), and reovirus (Reo). Maternal antibody titers for
      Newcastle disease virus (NDV) were measured using a hemagglutination inhibition
      test. Half-life estimates of maternal antibody titers were 5.3, 4.2, 7, 5.1, 3.9,
      3.8, 4.9, 4.1, 6.3, and 4.7 d for AEV, AIV, CAV, IBDV, IBV, ILTV, MG, MS, NDV,
      and Reo, respectively. The statistical analysis revealed significant differences
      among half-lives of maternal antibody titers against certain pathogens.
      Furthermore, all maternal antibody titers were depleted by 10 d of age except for
      IBDV. 

PMID- 23960116
TI  - Evaluation of effects of EarlyBird associated with FloraMax-B11 on Salmonella
      Enteritidis, intestinal morphology, and performance of broiler chickens.
AB  - A posthatch fasting period of 24 to 72 h is a common and inevitable practice in
      commercial poultry production. This delay in start of feed intake has been
      reported to negatively affect yolk utilization, gastrointestinal development,
      slaughter weight, breast meat yield, performance, and to also depress
      immunological development, making the birds more susceptible to infection from
      pathogens such as Salmonella. Furthermore, public concerns regarding the
      considerable human rates of illness reported and the emergence of antibiotic
      resistant strains of Salmonella have doubled the challenge on the poultry
      industry to find alternative means of Salmonella control. In the present study,
      we evaluated the effects of a combination of early feeding with probiotic
      supplementation on morphological development of mucosa, control of Salmonella,
      and overall performance in broiler chickens. We used a blend of a commercially
      available perinatal supplement, EarlyBird (EB; Pacific Vet Group USA Inc.,
      Fayetteville, AR), and a successful probiotic supplement, FloraMax-B11 (FM;
      Pacific Vet Group USA Inc.), to evaluate the effects on gut morphology,
      Salmonella intestinal colonization, and horizontal transmission, along with its
      effects on BW and related performance in broiler chickens under simulated
      commercial hatching management and shipping conditions. Morphometric analysis
      showed increased villus height, villus width, villus to crypt ratio, and villus
      surface area index in chickens treated with EB + FM groups. Significant
      reductions in Salmonella recovery, incidence, and horizontal transmission were
      also observed among the same groups, suggesting beneficial effects of early
      feeding and competitive exclusion by probiotic bacteria. Improved gut morphology
      and Salmonella exclusion was very well supported by BW data with significantly
      lower early BW loss and overall BW gains in birds treated with EB + FM mixture.
      The results of this study demonstrated that the combination of EB and FM improved
      gut morphology, reduced the amount of Salmonella that could be recovered, as well
      as improved BW when compared with controls and each product individually. These
      data address both animal welfare and food safety concerns faced by the poultry
      industry. 

PMID- 23960117
TI  - The effects of coarse ground corn, whole sorghum, and a prebiotic on growth
      performance, nutrient digestibility, and cecal microbial populations in broilers
      fed diets with and without corn distillers dried grains with solubles.
AB  - Two experiments were conducted from 0 to 21 d of age and evaluated diets
      containing combinations of fine or coarse ground corn (557 or 1,387 MUm,
      respectively), whole sorghum, 15% corn distillers dried grains with solubles
      (DDGS), or a prebiotic-type product containing yeast cell wall, lactose, citric
      acid, and other fermentable carbohydrates. In experiment 1, feed efficiency was
      decreased (P < 0.001) after the first week of age for broilers fed diets
      containing whole sorghum, whereas broilers receiving diets with 15% DDGS had
      increased feed efficiency (P < 0.03) compared with those receiving no DDGS. In
      the second experiment, BW gain was increased (P < 0.03) after the first week of
      age for broilers fed diets containing the prebiotic and DDGS compared with their
      respective controls. In experiment 1, the diet containing sorghum yielded the
      highest AMEn value (P < 0.03). In experiment 2, diets containing the combination
      of the prebiotic + DDGS yielded higher AMEn values (P < 0.004) at 7 and 21 d
      compared with diets containing no combination. The effects of diet on amino acid
      digestibility were generally small and inconsistent in both experiments. In
      experiment 1, broilers fed the coarse corn or whole sorghum diets had increased
      (P < 0.0001) relative gizzard weights compared with broilers fed the fine corn
      diet. Also, diets containing DDGS yielded increased relative gizzard weights (P <
      0.05) compared with diets containing no DDGS. In experiment 2, there was a
      decrease (P < 0.03) in cecal Escherichia coli when the combination of the coarse
      ground corn, prebiotic, and DDGS was fed in comparison with broilers receiving no
      prebiotic or DDGS. These results indicate that diets containing coarsely ground
      corn or whole sorghum in combination with DDGS can be fed to broilers with no
      long-term adverse effects on growth performance and nutrient digestibility and
      that these ingredients can have beneficial effects on AMEn, gizzard size, and
      cecal microflora in some instances. 

PMID- 23960118
TI  - Broilers fed dietary vitamins harbor higher diversity of cecal bacteria and
      higher ratio of Clostridium, Faecalibacterium, and Lactobacillus than broilers
      with no dietary vitamins revealed by 16S rRNA gene clone libraries.
AB  - Research on the interaction between dietary vitamins and intestinal bacteria is
      poorly understood. To investigate the effect of dietary vitamins on the cecal
      bacterial communities, 2 bacterial 16S rRNA gene clone libraries were constructed
      from pooled PCR products obtained from the cecal digesta of 28-d broilers fed
      diets with vitamins (V) at the NRC level or with no vitamins (NV). The results
      showed that BW gain and average feed intake of V broilers was significantly
      higher (P < 0.01) than NV broilers, whereas the feed/gain ratio was significantly
      lower (P < 0.01) in V broilers. A total of 188 and 185 clones were sequenced for
      the NV and V broilers, respectively. Sequence identity criterion of 98% was used
      to assign sequences to operational taxonomic units (OTU). Clones from the NV
      group broilers were assigned to 14 OTU, with 33% clones affiliated with the genus
      Clostridium, 19% affiliated with the genera Escherichia/Shigella, 14% affiliated
      with the genus Bacteroides, and the remaining clones (34%) affiliated with 5
      other bacterial genera (Faecalibacterium, Parasporobacterium, Ruminococcus,
      Streptococcus, and Subdoligranulum). Clones from the V group broilers were
      assigned to 23 OTU, with 46% of the clones affiliated with the genus Clostridium,
      11% affiliated with the genus Fecalibacterium, and the remaining clones (43%)
      affiliated with 8 other genera (Anaerofilum, Lactobacillus, Anaerotruncus,
      Oscillibacter, Alistipes, Gracilibacter, Acetivibrio, and Haloplasma). Three OTU
      assigned to Clostridium, Faecalibacterium, and Ruminoccus were shared between the
      2 libraries. Shannon diversity index showed the V broilers exhibited
      significantly higher bacterial diversity (P = 0.05), and Libshuff analysis
      indicated that the community structure between the 2 groups was significantly
      different (P < 0.0001). These results suggest that lack of dietary vitamins can
      increase the ratio of facultative pathogenic bacteria and decrease the diversity
      of bacteria in the cecum of broilers. Our results provide new leads for further
      investigations on the interaction between dietary vitamin additives and the gut
      health of broilers. 

PMID- 23960119
TI  - Comparative amino acid digestibility for broiler chickens and White Pekin ducks.
AB  - A total of 608 three-week-old male broiler chickens and White Pekin ducks were
      used in a 5-d trial to compare ileal amino acid (AA) digestibility of soybean
      meal (SBM) and canola meal (CM) using the regression method. A corn-casein
      cornstarch-based diet was mixed to contain 15% CP. Cornstarch was replaced with
      test ingredient (SBM or CM) to contain 18 or 21% of CP in 4 other diets. A
      nitrogen-free diet (NFD) was used for standardization of apparent digestibility.
      Birds received a standard starter diet (23% CP) from d 0 to 14 posthatch and then
      6 experimental diets for 5 d. On d 19 posthatch, birds were asphyxiated with
      CO(2), and digesta from the distal section of ileum was collected. The ileal
      digestibility of AA from the test ingredients was assessed by multiple linear
      regression analysis using data on daily apparent ileal digestible AA and total AA
      intakes. The basal endogenous losses of N and all AA for ducks were significantly
      higher than those for broilers. For ileal AA digestibility by regression of
      apparent digestible AA intake against AA intake, there was a higher (P < 0.05)
      digestibility for Cys and Pro in ducks compared with broilers (P < 0.05). Within
      species, digestibility was not different between SBM and CM except for Lys of
      ducks, and Lys and Pro of broilers (P < 0.05). The results of this study showed
      that ducks have higher basal endogenous AA losses compared with broiler chickens
      as well as higher ileal Cys and Pro digestibility estimates derived from
      regression approach, indicating that data obtained from broilers should not be
      used to formulate diets for ducks.

PMID- 23960120
TI  - Regulation of selenoprotein P concentration and expression by different sources
      of selenium in broiler breeders and their offspring.
AB  - An 8-wk experiment using 180 Lingnan Yellow broiler breeders was conducted to
      investigate the effect of different sources of Se on the concentration and gene
      expression of selenoprotein P (SEPP1) in broiler breeders and their offspring.
      After receiving a low-Se basal diet for 8 wk, broiler breeders were randomly
      allocated to 3 treatments (6 replicates per treatment) and fed corn-soy-based
      diets supplemented with 0.15 mg/kg of Se from sodium selenite (SS), Se-enriched
      yeast (SY), and selenomethionine (SM), respectively. Fertile eggs from different
      replicates were collected during the last week of the experiment and then
      incubated in different incubator trays in the same incubator. The concentrations
      and mRNA levels of SEPP1 were determined in liver and kidney of broiler breeders
      and their offspring, as well as the serum SEPP1 concentration. Compared with SS,
      both SY and SM significantly increased (P < 0.05) the concentration and mRNA
      level of SEPP1 in 1-d-old chicks. In broiler breeders, the serum and liver SEPP1
      concentrations were notably increased by the use of organic Se (P < 0.05),
      whereas no differences were found in the kidney. Moreover, the SEPP1 mRNA level
      in the liver was remarkably elevated (P < 0.05) in organic Se treatments, but
      also no differences were observed in the kidney. Results of this study indicate
      that the use of organic Se (SY or SM) in maternal diets is very effective for
      increasing the concentration and mRNA level of SEPP1, especially in their
      offspring. No differences between SY and SM were observed. 

PMID- 23960121
TI  - Additivity of amino acid digestibility in corn and soybean meal for broiler
      chickens and White Pekin ducks.
AB  - A total of 256 broiler chickens and 208 White Pekin ducks were used in a 5-d
      trial to test additivity of the apparent (AID) and standardized ileal
      digestibility (SID) of amino acids (AA) in corn and soybean meal (SBM). A
      nitrogen-free diet was used for standardization of apparent digestibility. Two
      diets contained corn or SBM as the sole source of CP and AA. Another diet was
      prepared by mixing corn and SBM. Chromic oxide was included as an indigestible
      marker. Birds received a standard starter diet from d 1 to 21 and thereafter the
      4 experimental diets for 5 d in a randomized complete block design. On d 26,
      digesta from the distal section of the ileum was collected. To test additivity of
      digestibility values, the difference between measured values in mixed diet and
      predicted values calculated with measured values in individual ingredients was
      examined. The estimated basal endogenous losses of N and AA were higher in ducks
      compared with broilers (P < 0.05). Regardless of species, the calculated
      proportion of basal endogenous losses of CP and AA in calculating SID was higher
      (P < 0.01) in corn than that in SBM. The measured AID of His, Leu, Lys, Met, Phe,
      Glu, Pro, and Tyr in mixed diets for broilers were higher than predicted values
      (P < 0.05), whereas measured and predicted SID did not differ except for Cys. For
      ducks, the differences between the measured and predicted AID were significant (P
      < 0.05) for CP and all AA except for 8 AA (Arg, Ile, Thr, Val, Asp, Gly, Pro, and
      Tyr). Similar to the result from broiler study, there was no difference between
      the predicted and measured SID of CP and all AA except for Cys. The results
      showed that AID of some AA for corn and SBM were not additive in the mixed diet,
      but SID values were additive irrespective of the ingredients and species used.
      Moreover, extent of difference between measured and predicted values in ducks
      were higher than that in broilers. 

PMID- 23960122
TI  - Influence of dietary inclusion of Bacillus licheniformis on laying performance,
      egg quality, antioxidant enzyme activities, and intestinal barrier function of
      laying hens.
AB  - This experiment was conducted to evaluate the effects of dietary inclusion of
      Bacillus licheniformis on laying performance, egg quality, antioxidant enzyme
      activities, and intestinal barrier function of laying hens. Hy-Line Variety W-36
      hens (n = 540; 28 wk of age) were randomized into 6 groups, each group with 6
      replications (n = 15). The control group received the basal diet formulated with
      maize and soybean meal. The treatment groups received the same basal diets
      supplemented with 0.01, 0.02, 0.03, 0.06, and 0.09% Bacillus licheniformis powder
      (2 * 10(10) cfu/g) for an 8-wk trial. The results showed that dietary
      supplementation with 0.01 and 0.03% B. licheniformis significantly increased egg
      production and egg mass. However, no significant differences were observed in egg
      weight, feed consumption, and feed conversion efficiency among the 6 groups.
      Supplementation with different levels of B. licheniformis was found to be
      effective in improvement of egg quality by increasing egg shell thickness and
      strength. Compared with control, d-lactate content, diamine oxidase activity, and
      adrenocorticotropic hormone level in serum decreased significantly, and the level
      of estradiol and follicle-stimulating hormone increased significantly in plasma
      of all the experimental groups. Dietary supplementation with B. licheniformis
      increased the intestinal villus height and reduced the crypt depth. In
      conclusion, dietary inclusion of B. licheniformis could improve laying
      performance and egg quality significantly in a dose-dependent manner by
      decreasing the stress response, upregulating the growth hormone, and improving
      intestinal health. 

PMID- 23960123
TI  - Transgenic chickens expressing human urokinase-type plasminogen activator.
AB  - Urokinase-type plasminogen activator is a serine protease that is clinically used
      in humans for the treatment of thrombolytic disorders and vascular diseases such
      as acute ischemic stroke and acute peripheral arterial occlusion. This study
      explored the feasibility of using chickens as a bioreactor for producing human
      urokinase-type plasminogen activator (huPA). Recombinant huPA gene, under the
      control of a ubiquitous Rous sarcoma virus promoter, was injected into the
      subgerminal cavity of freshly laid chicken eggs at stage X using the replication
      defective Moloney murine leukemia virus (MoMLV)-based retrovirus vectors
      encapsidated with VSV-G (vesicular stomatitis virus G) glycoprotein. A total of
      38 chicks, out of 573 virus-injected eggs, hatched and contained the huPA gene in
      their various body parts. The mRNA transcript of the huPA gene was present in
      various organs, including blood and egg, and was germ-line transmitted to the
      next generation. The level of active huPA protein was 16-fold higher in the blood
      of the transgenic chicken than in the nontransgenic chicken (P < 0.05). The
      expression of huPA protein in eggs increased from 7.82 IU/egg in the G0
      generation to 17.02 IU/egg in the G1 generation. However, huPA-expressing embryos
      had reduced survival and hatchability at d 18 and 21 of incubation, respectively,
      and the blood clotting time was significantly higher in transgenic chickens than
      their nontransgenic counterparts (P < 0.05). Furthermore, adult transgenic
      rooster showed reduced (P < 0.05) fertility, as revealed by reduced volume of
      semen ejaculate, sperm concentration, and sperm viability. Taken together, our
      data suggest that huPA transgenic chickens could be successfully produced by the
      retroviral vector system. Transgenic chickens, expressing the huPA under the
      control of a ubiquitous promoter, may not only be used as a bioreactor for
      pharming of the huPA drug but also be useful for studying huPA-induced bleeding
      and other disorders. 

PMID- 23960124
TI  - Marination and packaging impact on textural properties of home-frozen broiler
      breast fillets.
AB  - Different packaging is available to consumers, and marination is widely applied.
      However, their effects on the quality of broiler breast fillets during home
      freezing are not well known to consumers. Therefore, the objective of this study
      was to evaluate the effect of packaging materials on the quality of chicken
      breast fillets after 1, 3, and 6 wk storage at -18 degrees C. A total of 256
      fillet were randomly placed in tray packs, freezer bags, butcher paper, and
      nonpackaged controls. Samples were analyzed for raw pH, color, percent moisture
      content, and TBA reactive substances (TBARS) at d 0 (only nonpackaged controls),
      wk 1, 3, and 6, and cooked texture and sensory attributes at wk 1 and 6. There
      were differences (P < 0.05) in pH, color, percent moisture content, and texture
      among the treatments by wk 6, but no differences (P < 0.05) in TBARS values and
      the sensory evaluation (tenderness, juiciness, and overall flavor) were seen.
      Consumers were not able to detect quality differences (P < 0.05) among treatments
      despite analytical differences. Experiment 2 was conducted to evaluate the
      effects of marination on the quality of chicken breast fillets after 2 wk of
      storage in a home freezer (-18 degrees C). A total of 240 fillets were used in
      the treatments: nonmarinated fresh nonfrozen, nonmarinated frozen, marinated
      fresh nonfrozen, and marinated frozen. Fillets were vacuum-tumbled in a 10%
      solution yielding a final concentration of 0.45% sodium tripolyphosphate and
      0.65% salt in the meat. Raw samples were evaluated for color, TBARS, and thaw
      loss. Cooked samples after 2 wk of storage were analyzed for cook loss, texture,
      moisture, and sensory evaluation (color, juiciness, tenderness, overall flavor,
      and preference). Both marinated samples showed better (P < 0.05) quality in terms
      of L* value, TBARS, cook loss, texture, moisture content, and better sensory
      attributes (except color) than nonmarinated samples. Quality of marinated samples
      was not negatively affected by home freezing after 2 wk. 

PMID- 23960125
TI  - Effects of genistein and hesperidin on biomarkers of heat stress in broilers
      under persistent summer stress.
AB  - This study investigated the supplemental effects of the flavonoids genistein and
      hesperidin for biomarkers of heat stress in broilers reared under persistent
      summer stress. A total of 360 one-day-old, mixed-sex broiler chickens were
      divided into 6 treatment groups: control or supplemented with 5 mg of
      genistein*kg of feed(-1), 20 mg of hesperidin*kg of feed(-1), or a mixture of
      genistein and hesperidin (1:4) at a dosage of 5 mg*kg(-1), 10 mg*kg(-1), and 20
      mg*kg(-1) of feed. Broilers were slaughtered at 42 d and samples were analyzed
      for hematological profile, creatine kinase, lactate dehydrogenase, and heat shock
      protein 70 mRNA levels. Results showed that dietary genistein and hesperidin
      improved (P < 0.05) the weekly performance of broilers particularly during the
      finisher period. The circulating heterophils and heterophil-to-lymphocyte ratios
      were found to decrease (P < 0.01) in the treated groups. Moreover, biomarkers of
      heat stress including the level of creatine kinase, lactate dehydrogenase, and
      heat shock protein 70 mRNA of breast muscle was also changed (P < 0.01)
      positively by the dietary compounds with pronounced effects of combined
      treatments. These findings suggested that genistein and hesperidin could be a
      prime strategy to ameliorate summer stress effects in broilers; and a combination
      of both compounds may lead to mutual synergistic effects. It could be suggested
      that dietary use of both genistein and hesperidin as a feed supplement may offer
      a potential nutritional strategy in tropical and subtropical regions to overcome
      the deleterious effects of persistent summer stress in broiler production. 

PMID- 23960126
TI  - Uterine fluid proteins and egg quality characteristics for 2 commercial and 2
      heritage laying hen lines in response to manipulation of dietary calcium and
      vitamin D3.
AB  - The aim of this study was to evaluate the quality of eggs from 2 selected
      commercial strains of laying hens and 2 unselected lines of chickens fed diets
      with different combinations of Ca and vitamin D and relate it to the profile of
      uterine proteins and ultrastructure of the shell. A group of 4 chickens was
      housed in each of 24 cages. The group consisted of one representative from each
      of the following breeds: Lohmann LSL- Lite, Lohmann Classic-Brown, Fayoumi, and
      Light Sussex. Six dietary combinations of Ca and vitamin D(3) (3.35%, 2,500 IU;
      4.10%, 2,500 IU (control); 4.85%, 2,500 IU; 3.35%, 200 IU; 4.10%, 200 IU; and
      4.85%, 200 IU) were randomly assigned to 4 replicate cages for 2 treatment
      periods (26-29 and 56-59 wk of age). Data were analyzed as a split-plot design
      with cage as the main plot and hen as the subplot. Egg quality traits were
      different (P < 0.0001) between commercial and heritage breeds. Lohmann Brown had
      stronger shells with higher specific gravity compared with other breeds. Both
      commercial and heritage birds responded to a drop in vitamin D3 level by marked
      reduction in shell thickness. The SDS-PAGE profiles of uterine fluid samples
      revealed a decrease (P < 0.05) in 200-, 150-, 116-, and <=6.5-kDa proteins,
      whereas proteins with molecular weight (MW) of 80, 55, 52, 45, 42, and 28 kDa
      increased with bird age. A 36- and 52-kDa protein band was most intense for
      Fayoumi compared with other breeds. Ultrastructural characteristics showed
      flattened and deeply etched mammillary caps for Lohmann Brown and the presence of
      type A and type B bodies between mammillary cones in eggshells from Fayoumi and
      Lohmann Lite. The negative correlation between ultrastructural characteristics,
      which decrease with bird age, and the 116-kDa uterine protein band could provide
      insight into reduced eggshell quality as hens age.

PMID- 23960127
TI  - Characterization of muscle fiber type in the pectoralis major muscle of slow
      growing local and commercial chicken strains.
AB  - The study aimed to characterize muscle fiber type of the pectoralis major muscle
      of slow-growing chickens belonging to the Padovana local breed, the commercial
      strain Berlanda gaina, and their cross. Forty-five chickens (both males and
      females) from the different genotypes were grown up to 180 d. Histochemical and
      morphometrical analyses were performed to characterize muscle fiber types,
      myofiber density, and myofiber size of the different genotypes. The effects of
      genotype, sex, and their interaction were estimated. Muscle samples appeared
      almost entirely made up of IIB fiber type, whereas a low percentage of area (5 to
      6%) was composed of hypercontracted fiber. Myofiber density was significantly
      higher (P < 0.05) in Padovana strains and cross-sectional area was significantly
      lower (P < 0.01) than in Berlanda strain. Muscle fiber characteristics appeared
      not to be affected by the interaction of genotype * sex. 

PMID- 23960128
TI  - Comparison of breast muscle traits and meat quality characteristics in 2
      commercial chicken hybrids.
AB  - A trial was conducted to compare muscle traits and meat quality characteristics
      of the pectoralis muscle in 2 chicken commercial hybrids having standard (SBY)
      and high breast yield (HBY), respectively. A total of 2,124 one-day-old male
      chicks, equally divided into 2 experimental groups represented by strains (SBY
      and HBY), were grown using homogenous conditions and fed the same standard diets
      until reaching live weight of 4.2 kg at 53 and 55 d for the SBY and HBY groups,
      respectively. Thirty-six birds per each genotype were randomly selected, and
      their pectoralis major muscles were used to assess meat quality properties (color
      attributes, pH, drip loss, cook loss, Allo-Kramer shear values after cooking,
      moisture, proteins, total lipids, and ashes) as well as histological traits
      (cross-sectional area, frequency of abnormal fibers, and intramuscular fat
      infiltration). As expected, HBY genotype had higher breast yield (31.0 vs. 30.0%;
      P <= 0.05). Histological evaluations showed that HBY pectoralis muscles had
      higher cross-sectional fiber area coupled with a dramatically higher (P <= 0.001)
      incidence of abnormal fibers and more abundant infiltration of intramuscular fat.
      Moreover, histopathological anomalous features such as central nuclei,
      proliferation of endomysial and perimysial collagen, inflammatory infiltrate, and
      necrosis of the fibers were also observed. As for meat quality, SBY hybrid showed
      lower ultimate pH values (5.97 vs. 6.07; P <= 0.01), whereas overall color
      parameters were not affected by genotype. Breast meat from the HBY genotype also
      exhibited significantly lower ability to retain liquid during refrigerated
      storage (drip loss, 2.46 vs. 2.06%; P <= 0.05) and cooking (26.2 vs. 21.1%; P <=
      0.05) as well as higher shear-force values (2.59 vs. 2.11 kg/g; P <= 0.001).
      Finally, with regard to chemical composition, significant differences (P <= 0.05)
      were detected in protein (22.8 vs. 23.5%) and lipid (1.65 vs. 1.82%) contents,
      which were significantly lower in the HBY hybrid, whereas moisture content tended
      (P = 0.07) to be inferior in the SBY hybrid. 

PMID- 23960129
TI  - Effects of substituting yellow corn for sorghum in geese diets on magret and foie
      gras quality.
AB  - The aim of this trial was to study the effects of substitution of yellow corn
      with sorghum during the growing-finishing (G period), overfeeding (O period), or
      both periods on magret and foie gras quality in geese. In total, 260 ganders were
      divided into 4 groups (65 birds in each) differing in the cereal (yellow corn or
      sorghum) included in the diet given during the G and the O periods, using a 2 * 2
      factorial arrangement of treatments. The groups differed in the nature of the
      cereal in the diet offered to birds between 44 and 104 d of age (G period: a diet
      containing 500 g of sorghum/kg (SS and SC groups) or a diet containing 500 g of
      yellow corn/kg (CS and CC groups). The groups differed also in the diet offered
      to birds between 105 and 120 d of age (O period): 967 g of yellow corn/kg (SC and
      CC groups) or 965 g of sorghum/kg (SS and CS groups). At the end of the O period,
      the birds were slaughtered after 10 h of fasting to measure foie gras and breast
      muscle weight, color, and chemical composition. The mortality in the SC group was
      higher (P < 0.05) than in the other 3 groups (14.29 vs. 3.58%, average of the 3
      groups). After overfeeding, birds fed with sorghum had foie gras that were
      heavier 984 vs. 885 g, in CS+SS vs. CC+SC groups, respectively; P < 0.001) and
      less yellow (18.03 vs. 23.97 for b*, in CS+SS vs. CC+SC groups, respectively, P <
      0.001) than birds fed with corn. The substitution of yellow corn with sorghum
      during the G and O periods (SS group) increased the weight of the foie gras, but
      altered its color to a paler yellow. In contrast, a substitution during the G
      period only (SC group) resulted in increased mortality during the O period. 

PMID- 23960130
TI  - Salmonella penetration through eggshells of chickens of different genetic
      backgrounds.
AB  - Eggs have been identified as a source of salmonellosis, making the transmission
      of Salmonella to eggs of great concern to the poultry industry. The goal of this
      experiment was to determine the ability of Salmonella to penetrate the eggshell
      of 5 different breeds of noncommercial chicken, Barred Plymouth Rock, White
      Leghorn, Brown Leghorn, Fayoumi, and Light Sussex, and 1 commercial Lohmann LSL
      Lite. Egg weight, breaking force, shell weight, and shell thickness measurements
      were taken for 30 eggs per breed. A 1 cm in diameter hole was cut out from the
      narrow end of 30 additional eggs per breed. The shells were filled with plate
      count agar containing tetracycline and 0.1% 2,3,5-triphenyl terazolium chloride
      and sealed with paraffin wax. Agar-filled eggs were submerged for 1 min in an
      overnight culture of tetracycline-resistant Salmonella Heidelberg and incubated
      at 37 degrees C for 40 h. Eggs were candled and visual colonies were counted and
      reported as cfu per egg and cfu per gram of shell. The SAS mixed model was used
      to evaluate differences between breeds for egg quality characteristics and the
      number of cfu per egg and per gram of shell. Commercial layers (62.6 g) and
      Barred Plymouth Rock (61.5 g) produced the largest eggs, whereas Fayoumi (47.1 g)
      produced the smallest (P < 0.05). Force to break the shell was lowest (P < 0.05)
      for Barred Plymouth Rock (3.6 kg) and greatest for the commercial (4.4 kg), White
      Leghorn (4.4 kg), and Fayoumi (4.2 kg). Bacteria penetrating the shell was lowest
      (P < 0.05) for Barred Plymouth Rock (10.7 cfu/g) and highest for Light Sussex
      (27.7 cfu/g) and Brown Leghorn (27.2 cfu/g), with other breeds intermediate.
      These results indicate that there are breed-specific influences on the ability of
      an egg to resist Salmonella, which cannot be explained by shell quality
      measurements. Further investigations are warranted to determine the contributing
      factors to shell penetration by bacteria. This study highlights the value in
      maintaining heritage chicken breeds as a genetic resource for the future. 

PMID- 23960131
TI  - Physicochemical and functional properties of gelatins extracted from turkey and
      chicken heads.
AB  - Gelatins were prepared from chicken and turkey heads in a series of batch
      extractions at 2 different temperatures (50 and 60 degrees C), and their
      composition and functional properties were evaluated. Gelatin yield from chicken
      and turkey heads was 52.29 and 62.76%, respectively, on a dry weight basis
      relative to the total collagen content in the raw materials. The gel strength of
      turkey gelatins varied from 332.7 to 368.4 g, which was significantly (P < 0.05)
      higher than that of chicken gelatins. Both chicken and turkey head gelatins had
      high solubility at acidic and alkaline pH values. However, turkey head gelatins
      showed better emulsifying and foaming properties compared with chicken gelatins. 

PMID- 23960132
TI  - Effects on performance of ground wheat with or without insoluble fiber or whole
      wheat in sequential feeding for laying hens.
AB  - Sequential feeding (SF) is an innovative system for laying hens consisting of
      nutrients separating energy, protein, and calcium supplies to fulfill nutrient
      requirements at the relevant time of day. In previous studies, hens received
      whole wheat in the morning and a balancer diet (rich in protein and calcium) in
      the afternoon. To improve SF utilization, the aim was to substitute whole wheat
      in the morning by an alternative energy supply: ground wheat and ground corn,
      with or without a proportion of whole wheat and insoluble fiber. The goal was to
      obtain the advantages observed in previous experiments with whole wheat [bigger
      gizzard, thinner hens, reduced feed conversion ratio (FCR)]. Four hundred thirty
      two ISA Brown hens were housed in collective cages from 20 to 35 wk of age
      divided into 8 different treatments: a continuous control diet, a sequential diet
      with whole wheat in the morning, 3 wheat-based diets (ground wheat, ground wheat
      and 20% whole wheat, and ground wheat with 5% insoluble fiber) and 3 ground corn
      based (ground corn, ground corn and 20% whole wheat, and ground corn with 5%
      insoluble fiber) provided in the morning. All sequential regimens received the
      same balancer diet rich in protein and calcium in the afternoon. Whole wheat SF
      gave the best results with an improved FCR compared with continuous control and
      all other SF diets. Wheat- and corn-based diets showed intermediate results
      between whole wheat SF and continuous feeding. Gizzard weight was higher and hens
      were lighter than with conventional continuous feeding, leading to an average FCR
      improvement of 3.2% compared with a continuous control. Thus, it is possible in
      SF diets to substitute, at least partially, whole wheat by ground wheat or ground
      corn with added insoluble fiber or some whole wheat, allowing more flexibility
      and economic optimization. 

PMID- 23960133
TI  - Symposium: experimental design for poultry production and genomics research.
AB  - This symposium dealt with the theoretical and practical aspects of choosing and
      evaluating experimental designs, and how experimental results may be related to
      poultry production through modeling. Additionally, recent advances in techniques
      for generating high-throughput genomic sequencing data, genomic breeding values,
      genomics selection, and genome-wide association studies have provided unique
      computational challenges to the poultry industry. Such challenges were presented
      and discussed. 

PMID- 23960134
TI  - Experimental power considerations--justifying replication for animal care and use
      committees.
AB  - A common practice in poultry science is to compare new treatments with a control
      or between treatments tested in planned experiments. The overall F-test from an
      ANOVA of the data allows the researcher to reject or not reject the null
      hypothesis. However, the correct conclusion from such analysis depends on
      sufficient replicates being included in the experiment. On the other hand,
      restrictions are imposed to reduce the number of birds used in experiments for
      welfare reasons and to save scarce resources. We review the basic concepts needed
      to determine the number of replicates before conducting an experiment. We use
      these concepts to assess the results of several real experiments and to show what
      might be done in future experiments. We describe how to do the computations in R
      software. 

PMID- 23960135
TI  - Interpreting experimental data on egg production--applications of dynamic
      differential equations.
AB  - This contribution focuses on applying mathematical models based on systems of
      ordinary first-order differential equations to synthesize and interpret data from
      egg production experiments. Models based on linear systems of differential
      equations are contrasted with those based on nonlinear systems. Regression
      equations arising from analytical solutions to linear compartmental schemes are
      considered as candidate functions for describing egg production curves, together
      with aspects of parameter estimation. Extant candidate functions are reviewed, a
      role for growth functions such as the Gompertz equation suggested, and a function
      based on a simple new model outlined. Structurally, the new model comprises a
      single pool with an inflow and an outflow. Compartmental simulation models based
      on nonlinear systems of differential equations, and thus requiring numerical
      solution, are next discussed, and aspects of parameter estimation considered.
      This type of model is illustrated in relation to development and evaluation of a
      dynamic model of calcium and phosphorus flows in layers. The model consists of 8
      state variables representing calcium and phosphorus pools in the crop, stomachs,
      plasma, and bone. The flow equations are described by Michaelis-Menten or mass
      action forms. Experiments that measure Ca and P uptake in layers fed different
      calcium concentrations during shell-forming days are used to evaluate the model.
      In addition to providing a useful management tool, such a simulation model also
      provides a means to evaluate feeding strategies aimed at reducing excretion of
      potential pollutants in poultry manure to the environment. 

PMID- 23960136
TI  - Interpreting experiments on egg production--statistical considerations.
AB  - A given data set can be analyzed many ways, but only one is the correct analysis
      based on the design actually used when running the experiment. This work gives a
      tutorial-like illustration of the effects of the presence of a regression
      variable (or covariate) on the recorded responses in an experiment set up as a
      standard factorial design and shows how the analysis results are to be adjusted
      for the presence of covariates. An underlying assumption of a factorial model is
      that each of the treatments (e.g., diets) is randomly allocated to different
      subjects (hens). When many measurements (e.g., over time) are made on the same
      subject (hen), this independence assumption is violated; in these cases, the
      design is an example from the class of repeated measures designs. The difference
      in analysis between factorial designs and repeated measures designs is also
      discussed. Then, the 2 concepts are merged wherein the results for a repeated
      measures analysis have to be adjusted for the presence of covariates. The paper
      concludes with analyses on the results of egg production responses from an
      experiment in which repeated measurements were made on the same hens and in which
      an unanticipated temperature covariate was present. 

PMID- 23960137
TI  - From data to function: functional modeling of poultry genomics data.
AB  - One of the challenges of functional genomics is to create a better understanding
      of the biological system being studied so that the data produced are leveraged to
      provide gains for agriculture, human health, and the environment. Functional
      modeling enables researchers to make sense of these data as it reframes a long
      list of genes or gene products (mRNA, ncRNA, and proteins) by grouping based upon
      function, be it individual molecular functions or interactions between these
      molecules or broader biological processes, including metabolic and signaling
      pathways. However, poultry researchers have been hampered by a lack of functional
      annotation data, tools, and training to use these data and tools. Moreover, this
      lack is becoming more critical as new sequencing technologies enable us to
      generate data not only for an increasingly diverse range of species but also
      individual genomes and populations of individuals. We discuss the impact of these
      new sequencing technologies on poultry research, with a specific focus on what
      functional modeling resources are available for poultry researchers. We also
      describe key strategies for researchers who wish to functionally model their own
      data, providing background information about functional modeling approaches, the
      data and tools to support these approaches, and the strengths and limitations of
      each. Specifically, we describe methods for functional analysis using Gene
      Ontology (GO) functional summaries, functional enrichment analysis, and pathways
      and network modeling. As annotation efforts begin to provide the fundamental data
      that underpin poultry functional modeling (such as improved gene identification,
      standardized gene nomenclature, temporal and spatial expression data and gene
      product function), tool developers are incorporating these data into new and
      existing tools that are used for functional modeling, and cyberinfrastructure is
      being developed to provide the necessary extendibility and scalability for
      storing and analyzing these data. This process will support the efforts of
      poultry researchers to make sense of their functional genomics data sets, and we
      provide here a starting point for researchers who wish to take advantage of these
      tools. 

PMID- 23960138
TI  - Experiences with a single-step genome evaluation.
AB  - Genomic selection can be implemented based on the genomic relationship matrix
      (GBLUP) and can be combined with phenotypes from nongenotyped animals through the
      use of best linear unbiased prediction (BLUP). A common method to combine both
      sources of information involves multiple steps, but is difficult to use with
      complicated models and is nonoptimal. A simpler method, termed single-step GBLUP,
      or ssGBLUP, integrates the genomically derived relationships (G) with population
      based pedigree relationships (A) into a combined relationship matrix (H) and
      allows for genomic selection in a single step. The ssGBLUP method is easy to
      implement and uses standard BLUP-based programs. Experiences with field data in
      chickens, pigs, and dairy indicate that ssGBLUP is more accurate yet much simpler
      than multi-step methods. The current limits of ssGBLUP are approximately 100,000
      genotypes and 18 traits. Models involving 10 million animals have been run
      successfully. The inverse of H can also be used in existing programs for
      parameter estimationm, but a properly scaled G is needed for unbiased estimation.
      Also, as genomic predictions can be converted to SNP effects, ssGBLUP is useful
      for genomic-wide association studies. The single-step method for genomic
      selection translates the use of genomic information into standard BLUP, and
      variance-component estimation programs become a routine. 

PMID- 23960139
TI  - Misclassification in binary responses and effect on genome-wide association
      studies.
AB  - Misclassification of dependent variables is a major issue in many areas of
      science that can arise when indirect markers are used to classify subjects or
      continuous traits are treated as categorical. In human medicine, this can have
      significant impacts on diagnostic accuracy. In animal science applications,
      misclassification can negatively affect both the accuracy of selection and the
      ability to ascertain the biological mechanisms for traits of interest. When
      dealing with traits influenced by genetic factors, genomic markers, such as SNP,
      can provide direct measurements of the underlying mechanisms controlling
      phenotypic responses. Unfortunately, in the presence of misclassification in the
      discrete dependent variables, the robustness of the analysis and the validity of
      the results could be severely compromised. To quantify the impact of
      misclassification on genome-wide association studies for binary responses, a real
      databased simulation was carried out. The simulated data consisted of 2,400
      animals genotyped for 50K SNP. A binary trait with heritability equal to 0.10 and
      prevalence of 20% was generated. A rate of 1, 5, and 10% misclassification was
      artificially introduced to the true binary responses. Using a latent-threshold
      model, 3 analyses were carried out for each misclassification rate using 1) the
      true data (M1), 2) the contaminated data and ignoring misclassification (M2), and
      3) the contaminated data and accounting for misclassification (M3). The results
      indicate that ignoring misclassification, when it exists in the data such as in
      M2, will lead to major deterioration in the performance of the model. When
      misclassification was contemplated in the model (M2), the results indicated a
      strong capacity of the procedure in dealing with potential misclassification in
      the training set. In fact, a large portion of miscoded samples in the training
      set was identified and corrected. The results of this study suggest that the
      proposed method is adequate and effective for practical genome-wide association
      studies for binary response classification. 

PMID- 23960140
TI  - Applying complex models to poultry production in the future--economics and
      biology.
AB  - The ability to determine the optimal broiler feed nutrient density that maximizes
      margin over feeding cost (MOFC) has obvious economic value. To determine optimal
      feed nutrient density, one must consider ingredient prices, meat values, the
      product mix being marketed, and the projected biological performance. A series of
      8 feeding trials was conducted to estimate biological responses to changes in ME
      and amino acid (AA) density. Eight different genotypes of sex-separate reared
      broilers were fed diets varying in ME (2,723-3,386 kcal of ME/kg) and AA (0.89
      1.65% digestible lysine with all essential AA acids being indexed to lysine)
      levels. Broilers were processed to determine carcass component yield at many
      different BW (1.09-4.70 kg). Trial data generated were used in model constructed
      to discover the dietary levels of ME and AA that maximize MOFC on a per broiler
      or per broiler annualized basis (bird * number of cycles/year). The model was
      designed to estimate the effects of dietary nutrient concentration on broiler
      live weight, feed conversion, mortality, and carcass component yield. Estimated
      coefficients from the step-wise regression process are subsequently used to
      predict the optimal ME and AA concentrations that maximize MOFC. The effects of
      changing feed or meat prices across a wide spectrum on optimal ME and AA levels
      can be evaluated via parametric analysis. The model can rapidly compare both
      biological and economic implications of changing from current practice to the
      simulated optimal solution. The model can be exploited to enhance decision making
      under volatile market conditions. 

PMID- 23960141
TI  - Ureaplasma species: role in neonatal morbidities and outcomes.
AB  - The genital mycoplasma species, Ureaplasma parvum and Ureaplasma urealyticum are
      the most common organisms isolated from infected amniotic fluid and placentas,
      and they contribute to adverse pregnancy outcomes including preterm birth and
      neonatal morbidities. In our institution, almost half of the preterm infants of
      less than 32 weeks gestation are Ureaplasma-positive in one or more compartment
      (respiratory, blood and/or cerebrospinal fluid), indicating that these organisms
      are the most common pathogens affecting this population. This review will focus
      on the compelling epidemiological and experimental evidence linking perinatal
      Ureaplasma species exposure to important morbidities of prematurity, such as
      bronchopulmonary dysplasia, intraventricular haemorrhage and necrotising
      enterocolitis. 

PMID- 23960142
TI  - Quantification of cell surface proteins with bispecific antibodies.
AB  - Flow cytometry is an established method for fast and accurate quantitation of
      cellular protein levels and requires fluorescently labeled antibodies as well as
      calibration standards. A critical step for quantitation remains the production of
      suitable detection antibodies with a precisely defined ratio of antigen-binding
      sites to fluorophores. Problems often arise as a consequence of inefficient and
      unspecific labeling which can influence antibody properties. In addition, the
      number of incorporated fluorophores necessitates a special normalization step for
      quantitation. To address these problems, we constructed different mono- and
      bivalent bispecific antibodies with binding site(s) for the cell surface
      antigens, cMET, EGFR1/HER1, ErbB2/HER2 or ErbB3/HER3 and with an additional
      digoxigenin-binding single-chain Fv fusion. The fluorophore Cy5 was covalently
      coupled to digoxigenin and quantitatively bound by the bispecific antibody. A
      panel of tumor cell lines was assessed under different culture conditions for
      absolute receptor expression levels of the indicated antigens and the data were
      set in relation to mRNA, gene count and immunoblot data. We could reproducibly
      quantify these receptors, omit the otherwise required normalization step and
      demonstrate the superiority of a 1 + 1 bispecific antibody. The same antibodies
      were also used to quantify the number of proteins in intracellular vesicles in
      confocal microscopy. The antibodies can be stored like regular antibodies and can
      be coupled with different digoxigenin-labeled fluorophores which makes them
      excellent tools for FACS and imaging-based experiments. 

PMID- 23960143
TI  - Jody Rosenblatt: to extrude apically or basally, that is the question. Interview
      by Caitlin Sedwick.

PMID- 23960144
TI  - Aurora B and Kif2A control microtubule length for assembly of a functional
      central spindle during anaphase.
AB  - The central spindle is built during anaphase by coupling antiparallel
      microtubules (MTs) at a central overlap zone, which provides a signaling scaffold
      for the regulation of cytokinesis. The mechanisms underlying central spindle
      morphogenesis are still poorly understood. In this paper, we show that the MT
      depolymerase Kif2A controls the length and alignment of central spindle MTs
      through depolymerization at their minus ends. The distribution of Kif2A was
      limited to the distal ends of the central spindle through Aurora B-dependent
      phosphorylation and exclusion from the spindle midzone. Overactivation or
      inhibition of Kif2A affected interchromosomal MT length and disorganized the
      central spindle, resulting in uncoordinated cell division. Experimental data and
      model simulations suggest that the steady-state length of the central spindle and
      its symmetric position between segregating chromosomes are predominantly
      determined by the Aurora B activity gradient. On the basis of these results, we
      propose a robust self-organization mechanism for central spindle formation. 

PMID- 23960147
TI  - Susac's syndrome: an immune mediated endotheliopathy laden with challenges and
      controversies.
AB  - Susac's syndrome is a microangiopathy of the retina, inner ear and brain
      manifesting as a triad of encephalopathy, hearing loss and branch retinal artery
      occlusion. The pathological mechanism is thought to be an immune-mediated small
      vessel vasculitis with some pathophysiological similarity to dermatomyositis.
      Awareness and early recognition of this syndrome is important as early treatment
      with immunosuppression can minimise cognitive, audiological and visual sequelae.
      We report a case of a 33-year-old woman who presented with the characteristic
      syndrome. She was treated with immunomodulatory therapy and remains well 2 years
      postpresentation with no new events. 

PMID- 23960145
TI  - The Bruchpilot cytomatrix determines the size of the readily releasable pool of
      synaptic vesicles.
AB  - Synaptic vesicles (SVs) fuse at a specialized membrane domain called the active
      zone (AZ), covered by a conserved cytomatrix. How exactly cytomatrix components
      intersect with SV release remains insufficiently understood. We showed previously
      that loss of the Drosophila melanogaster ELKS family protein Bruchpilot (BRP)
      eliminates the cytomatrix (T bar) and declusters Ca(2+) channels. In this paper,
      we explored additional functions of the cytomatrix, starting with the biochemical
      identification of two BRP isoforms. Both isoforms alternated in a circular array
      and were important for proper T-bar formation. Basal transmission was decreased
      in isoform-specific mutants, which we attributed to a reduction in the size of
      the readily releasable pool (RRP) of SVs. We also found a corresponding reduction
      in the number of SVs docked close to the remaining cytomatrix. We propose that
      the macromolecular architecture created by the alternating pattern of the BRP
      isoforms determines the number of Ca(2+) channel-coupled SV release slots
      available per AZ and thereby sets the size of the RRP. 

PMID- 23960148
TI  - Renal denervation in fibromuscular dysplasia.
AB  - Renal denervation offers novel treatment opportunities in patients with resistant
      hypertension, including cases with rare causes (fibromuscular dysplasia),
      warranting further investigation. 

PMID- 23960149
TI  - Invasive pneumococcal disease complicated by cerebral vasculitis, transient
      diabetes insipidus and spondylodiscitis.
AB  - Invasive pneumococcal disease (IPD) is a potential life-threatening situation
      that requires immediate recognition and treatment. Cerebrovascular complications
      are uncommon and have been reported less frequently in adults than in children.
      We report a case of 59-year-old man with IPD complicated by cerebral vasculitis,
      transient central diabetes insipidus and spondylodiscitis. Each of these
      complications is rare and needs specific approach. Their association is even
      rarer and to the best of our knowledge this is the first case reported. 

PMID- 23960150
TI  - Delayed postirradiation camptocormia.
AB  - Radiotherapy may cause central or peripheral nervous system complications,
      reported examples being myelopathy, brachial/lumbosacral plexopathies or
      predominantly motor lumbosacral radiculopathy. In the literature some studies
      regard camptocormia as a paravertebral myopathy and others as of neurogenic
      origin. We present a patient who developed camptocormia, 42 years after radiation
      therapy to the para-aortic and inguinal area. 

PMID- 23960152
TI  - Endometriosis of extra-pelvic round ligament, a diagnostic dilemma for
      physicians.
AB  - A 49-year-old multiparous woman presented with a swelling in the left groin of 6
      months duration. The swelling was associated with a dull aching pain. The patient
      reported increase in size of the swelling during lifting of heavy weights.
      Menstrual history was normal and there was no increase in pain over the swelling
      during menstruation. She underwent a caesarean section 20 years ago and the scar
      had healed by primary intention. She was provisionally diagnosed to have a left
      sided inguinal hernia. Ultrasonography showed a multiloculated cyst measuring
      5.3*1.5*5.2 cm within the inguinal canal. The patient had excision of the cyst
      under spinal anaesthesia. Intraoperatively the cyst was found to arise from the
      left round ligament. It measured 7*6 cm extending to the left lateral vaginal
      wall. Histopathology revealed endometriosis of the round ligament. Her
      gynaecological assessment was normal and they recommended no further treatment.
      On follow-up the patient was asymptomatic and wound had healed well. 

PMID- 23960151
TI  - Sustained antidepressant response to ketamine.
AB  - Case series outlining the treatment of three patients with ketamine, in which two
      of the patients had a sustained antidepressant effect to ketamine without the
      need for maintenance on antidepressants. These two responders have an established
      diagnosis of bipolar affective disorder with a history of response to
      electroconvulsive therapy and lithium, both of which have an influence on the
      seizure threshold as has ketamine. The mechanism of action of ketamine is yet
      unclear and although the current focus is on the N-methyl-d-aspartate and alpha
      amino-3-4-hydroxy-5methyl-4-isoxazoleproprionic acid receptors, we additionally
      recommend that its impact on the seizure threshold should be explored with a view
      to fully elucidating the mechanism of action. 

PMID- 23960153
TI  - Idiopathic acquired dacryocystocele treated with endonasal endoscopic
      dacryocystorhinostomy.
AB  - A 64-year-old woman presented with a medial canthal mass in her left eye, which
      was accompanied only by mild epiphora. There was no history of dacryocystitis,
      bloody tears, midfacial trauma or surgery. Physical examination showed a non
      inflammatory, subcutaneous, immobile mass below the level of the medial canthal
      tendon. Lacrimal irrigation demonstrated blockage at the nasolacrimal duct. A CT
      revealed a non-enhancing, low density, cystic lesion in the inferomedial aspect
      of the left orbit without bony erosion, which was compatible with an idiopathic
      acquired dacryocystocele. The patient underwent endonasal endoscopic
      dacryocystorhinostomy (DCR) and silicone intubation. Epiphora resolved
      immediately after surgery. Two years after surgery, the patient has had no
      recurrence of either the epiphora or the orbital. Idiopathic acquired
      dacryocystocele associated only with epiphora without accompanying dacryocystitis
      although rare should be considered in the differential diagnosis of acquired non
      inflammatory medial canthal masses. Endonasal endoscopic DCR represents a safe
      and effective treatment. 

PMID- 23960154
TI  - Diagnostic challenge of a complication of pneumoconiosis.

PMID- 23960155
TI  - Referral quality and the cooperation between hospital physicians and general
      practice: the role of physician and primary care factors.
AB  - AIMS: It has been shown that referral letters from GPs often are of poor quality,
      but research in this field is scarce, and few efforts have been made to
      investigate the factors that may help explain the variation in referral quality.
      METHODS: Combining a survey among 1298 Norwegian hospital physicians (response
      rate: 52%) with information on the hospitals and the communities they are
      serving, this study investigates how they view the general quality of patient
      referrals received from GPs, and the extent to which insufficient information in
      referrals and inappropriate referrals is considered a problem for cooperation
      with GPs. RESULTS: Only 15.6% of the hospital physicians perceived the quality of
      the referrals to be "usually good", and both lack of information in referrals and
      inappropriate referrals are seen as important barriers to cooperation with GPs.
      Of the individual factors, former GP practice is associated with a positive view
      on referral quality, while regular meetings between hospital physicians and GPs
      seem to reduce the problems of inappropriate and incomplete referrals.
      Furthermore, both average number of patients on GPs' lists and lack of free
      capacity in nursing and care institutions in the hospital catchment area was
      found to be negatively associated with perceived referral quality. CONCLUSIONS:
      There is a need to increase the knowledge on how contextual, institutional and
      professional factors affect coordination of care. The main contribution of this
      study lies in the attempt to address the macro and micro barriers of obtaining
      good referral care.

PMID- 23960156
TI  - A nordic charter for universal design.
AB  - AIMS: The aim of this paper is to present the result of a pioneer project; A
      Nordic Charter for Universal Design, which was initiated by the Norwegian
      Directorate for Children, Youth and Family Affairs in 2011. The purpose of the
      Charter was to present rationales that stated prerequisites for successful
      investment in Universal Design, and to establish a platform for further research
      and good practice. It was also meant to contribute to spreading of information
      and knowledge about the importance of guidance by the concept of Universal Design
      of initiatives with effects on the public arena. METHOD: A Nordic group of
      researchers and professionals in the field ended up after 8 months of work with a
      written document: "A Nordic Charter for Universal Design", which was presented at
      the International Conference in Universal Design in Oslo, Norway (UD 2012).
      RESULT: A Nordic Charter for Universal Design. CONCLUSIONS: Persons with
      disabilities often experience the public arenas environments, products and
      services as poorly-designed to fit their abilities and/or their needs. Together
      with the demographic changes in the Nordic societies with an increasing number of
      elderly people, it needs initiatives to improve independence, accessibility and
      participation in society. A strategy which aims to make design and composition of
      different environments, products, communication, information technology and
      services accessible, usable and understandable to as many as possible is
      Universal Design.

PMID- 23960157
TI  - The impact of organizational culture on the outcome of hospital care: after the
      implementation of person-centred care.
AB  - AIMS: To measure the effect of organizational culture on health outcomes of
      patients 3 months after discharge. METHODS: a quantitative study using
      Organizational Values Questionnaire (OVQ) and a health-related quality of life
      instrument (EQ-5D). A total of 117 nurses, 69% response rate, and 220 patients
      answered the OVQ and EQ-5D, respectively. RESULTS: The regression analysis showed
      that; 16% (R(2) = 0.02) of a decreased health status, 22% (R(2) = 0.05) of
      pain/discomfort and 13% (R(2) = 0.02) of mobility problems could be attributed to
      the combination of open system (OS) and Human Relations (HR) cultural dimensions,
      i.e., an organizational culture being dominated by flexibility. CONCLUSIONS: The
      results from the present study tentatively indicated an association between an
      organizational culture and patients' health related quality of life 3 months
      after discharge. Even if the current understanding of organizational culture,
      which is dominated by flexibility, is considered favourable when implementing a
      new health care model, our results showed that it could be hindering instead of
      helping the new health care model in achieving its objectives.

PMID- 23960158
TI  - Childhood poverty and blood pressure reactivity to and recovery from an acute
      stressor in late adolescence: the mediating role of family conflict.
AB  - OBJECTIVE: Childhood deprivation is inimical to health throughout the life
      course. Early experiences of stress could play a role in health inequalities. An
      important aspect of childhood poverty that has not received much attention is
      cardiovascular reactivity to and recovery from acute stressors. METHODS:
      Piecewise, multilevel growth curve regression was used to examine blood pressure
      reactivity to and recovery from a mental arithmetic task among late adolescents
      (mean [standard deviation] = 17.3 [1.0] years, n = 185) as a function of early
      childhood poverty (9 years). We also tested whether exposure to family conflict
      at age 13 years mediated expected linkages between childhood poverty and
      adolescent blood pressure reactivity and recovery to an acute stressor. RESULTS:
      Blood pressure reactivity was unaffected by household income during childhood,
      but late adolescents with lower household income during childhood showed slower
      systolic (b = -0.29, p = .004) and diastolic (b = -0.19, p = .002) recovery.
      These results include age and sex as statistical covariates. The significant
      poverty impact on systolic but not on diastolic blood pressure recovery was
      mediated by exposure to family conflict (95% confidence interval = - 0.1400 to -
      0.0012). CONCLUSIONS: We show that late adolescents who grew up in poverty have
      delayed blood pressure recovery from an acute stressor. Furthermore, childhood
      exposure to family conflict, a well-documented component of early childhood
      deprivation, accounted for some of the adverse effects of childhood poverty on
      stressor recovery among these adolescents. We discuss the importance of
      considering physiological stress accompanying early experiences of deprivation in
      thinking about health inequalities.

PMID- 23960159
TI  - The association of depressive symptoms and pulmonary function in healthy adults.
AB  - OBJECTIVE: Chronic lung disease is exacerbated by comorbid psychiatric issues and
      treatment of depression may improve disease symptoms. We sought to add to the
      literature as to whether depression is associated with pulmonary function in
      healthy adults. METHODS: In 2551 healthy adults from New York State, we studied
      the association of depression via the Center for Epidemiologic Studies Depression
      scale (CES-D) scale score and forced expiratory volume in 1 second (FEV1) and
      forced vital capacity (FVC) using general linear models and a cross-sectional
      design. RESULTS: We identified statistically significant inverse trends in FEV1,
      FVC, FEV1%, and FVC% by CES-D category, especially in ever-smokers and men. When
      adjusted for covariates, the difference in FEV1 and FEV1% for smokers with more
      than 18.5 lifetime pack-years from CES-D scores 0 to 3 to 16 or more (depressed)
      is approximately 0.25 l and 5.0% (adjusted p values for trend are <.001 and .019,
      respectively). In men, we also observed statistically significant inverse trends
      in pulmonary function with increasing CES-D. CONCLUSIONS: We identified an
      inverse association of depressive symptoms and pulmonary function in healthy
      adults, especially in men and individuals with a heavy smoking history. Further
      studies of these associations are essential for the development and tailoring of
      interventions for the prevention and treatment of chronic lung disease.

PMID- 23960160
TI  - Infection load as a predisposing factor for somatoform disorders: evidence from a
      Dutch General Practice Registry.
AB  - OBJECTIVE: Somatoform disorders (SDs) are characterized by chronic multiple
      functional somatic (FS) symptoms. It has been suggested that infections may be
      triggers for FS symptoms to occur, pointing to the immune system as a pathogenic
      factor in their development. The current study aimed to compare the prevalence of
      infections (i.e., infection load) in the history of patients with SDs with that
      of matched controls. METHODS: Samples (n = 185) were identified in the
      Psychiatric Case Register Middle Netherlands and the Julius General Practitioners
      Network. Patients with an SD diagnosis in the Psychiatric Case Register Middle
      Netherlands were compared with matched persons without somatoform complaints
      (controls) on their infection load in two periods before the date of the
      psychiatric diagnosis or a matched date for the controls (i.e., the total period
      for which data were available and a 3-year period). Infection load was defined as
      the total number of infections documented in the Julius General Practitioners
      Network. RESULTS: Patients with SD had significantly more infections than did
      controls in both periods (total period: mean [standard error] = 0.87 [0.10]
      versus 0.51 [0.06], z = -3.08, p = .002; 3-year period: 3.44 [0.47] versus 2.15
      [0.50], z = -2.91, p = .004). CONCLUSIONS: Results show that patients with SD
      have a higher infection load preceding their diagnosis as compared with matched
      controls, implicating that infection load may indeed predispose for developing FS
      symptoms. These findings emphasize the importance of further research on
      immunological mechanisms in FS symptoms. Limitations of the study are discussed.

PMID- 23960161
TI  - Effects of acute and chronic stress on the L-arginine nitric oxide pathway in
      black and white South Africans: the sympathetic activity and ambulatory blood
      pressure in Africans study.
AB  - OBJECTIVE: This study investigated the impact of stress on effectors of the L
      arginine/nitric oxide (NO) system including the endogenous inhibitor asymmetric
      dimethylarginine (ADMA). METHODS: Black (n = 168) and white (n = 206) South
      African teachers were exposed to a mental and a physical stressor for 1 minute,
      respectively. Serum samples for determination of l-arginine, NO metabolites,
      ADMA, and symmetric dimethylarginine (SDMA) were obtained at rest and during
      stress exposure. Perception of task stressfulness was assessed on a 7-point
      Likert scale, and psychological distress was estimated by the General Health
      Questionnaire. RESULTS: Black South Africans exhibited higher resting levels of
      NO metabolites (adjusted mean [standard error of the mean] = 11.3 [1.3] versus
      3.9 [1.1] MUmol/l, p < .001) but lower circulating ADMA (0.62 [0.02] versus 0.70
      [0.02] MUmol/l, p = .004) and SDMA (0.41 [0.01] versus 0.53 [0.01] MUmol/l, p <
      .001) than did white South Africans. Ethnicity-by-psychological distress
      interaction was observed for resting levels of ADMA (p = .002), SDMA (p = .038),
      and L-arginine (p = .048). Ethnic differences in responses to experimental stress
      were evident for NO metabolites (blacks versus whites: 5.94 [1.55] versus -0.74
      [1.25] MUmol/l, p = .004) and SDMA (blacks versus whites: -0.02 [0.01] versus
      0.02 [0.01] MUmol/l, p = .004). Ethnicity-by-psychological distress interaction
      for stress responses was found for l-arginine/ADMA ratio (p = .027). CONCLUSIONS:
      The l-arginine/NO system is affected by psychosocial distress with higher
      susceptibility in black South Africans. This interaction may contribute to the
      higher cardiovascular disease risk in black South Africans.

PMID- 23960162
TI  - Regulatory forum opinion piece*: pathology peer review--dilemmas of
      documentation.

PMID- 23960163
TI  - Biliary proliferative lesions in the Sprague-Dawley rat: adverse/non-adverse.
AB  - Whether biliary proliferative lesions in nonclinical species are predictive of
      potential hepatotoxicity in humans depends, at least in part, on the nature and
      severity of such changes in the nonclinical species. We reviewed published
      literature (clinical and nonclinical) and experimental data from rat toxicology
      studies conducted by GlaxoSmithKline and the National Institute of Environmental
      Health Sciences' National Toxicology Program in an effort to better characterize
      the relative risk of hepatobiliary effects in humans. Available evidence supports
      the interpretation that minimal "typical" appearing bile duct hyperplasia limited
      to the portal triads may be considered non-adverse in the rat and is of little to
      no concern to humans. The toxicological relevance of mild to moderate "typical"
      hyperplasia is less certain, and may be considered adverse in the rat and
      potentially pose a risk for humans, particularly if accompanied by evidence of
      hepatobiliary injury or functional compromise. In addition, any proliferative
      lesion that includes atypical or dysplastic epithelial changes, oval cell
      proliferation, and/or significant extension beyond the portal tracts is
      considered more ominous and may be considered adverse in the rat. 

PMID- 23960165
TI  - Regulatory forum opinion piece: what are pathology raw data?

PMID- 23960166
TI  - Regulatory forum opinion piece*: pathology peer review--to lock or not to lock,
      is that really the question?

PMID- 23960167
TI  - The 26-week Tg.rasH2 mice carcinogenicity studies: microscopic examination of
      only select tissues in low- and mid-dose groups.
AB  - A typical 26-week Tg.rasH2 mouse carcinogenicity study usually has 4 dose groups,
      composed of 25 mice/sex, which include 1 control and 3 test article-treated
      groups. In every study, there is a protocol required full tissue list of 49
      tissues which is examined microscopically in all animals of these 4 dose groups.
      Based on retrospective analysis of the historical control data collected from
      studies conducted in Tg.rasH2 mice from 2004 to 2012, we propose that a full
      tissue list be examined as usual in the control and high-dose groups; however, in
      the low- and mid-dose groups, only select tissues should be examined. The select
      tissue list is generated after analyzing common tumors, uncommon tumors seen
      grossly, uncommon tumors not seen grossly, organ weight variations with
      accountable microscopic lesions, and target organs identified in the high-dose
      groups. The proposed changes to the International Conference on Harmonization S1
      guidance may lead to an increased need for 26-week Tg.rasH2 mice studies. The
      time savings resulting from processing and evaluating a select tissue list rather
      than a full tissue list from low- and mid-dose groups of Tg.rasH2 mouse studies
      will further accelerate early completion of these studies without compromising
      the quality and integrity. 

PMID- 23960164
TI  - Toxicity and carcinogenicity studies of Ginkgo biloba extract in rat and mouse:
      liver, thyroid, and nose are targets.
AB  - Ginkgo biloba extract (GBE) is a popular herbal supplement that is used to
      improve circulation and brain function. In spite of widespread human exposure to
      relatively high doses over potentially long periods of time, there is a paucity
      of data from animal studies regarding the toxicity and carcinogenicity associated
      with GBE. In order to fill this knowledge gap, 3-month and 2-year toxicity and
      carcinogenicity studies with GBE administered by oral gavage to B6C3F1/N mice and
      F344/N rats were performed as part of the National Toxicology Program's Dietary
      Supplements and Herbal Medicines Initiative. The targets of GBE treatment were
      the liver, thyroid, and nose. These targets were consistent across exposure
      period, sex, and species, albeit with varying degrees of effect observed among
      studies. Key findings included a notably high incidence of hepatoblastomas in
      male and female mice and evidence of carcinogenic potential in the thyroid gland
      of both mice and rats. Various nonneoplastic lesions were observed beyond control
      levels in the liver, thyroid gland, and nose of rats and mice administered GBE.
      Although these results cannot be directly extrapolated to humans, the findings
      fill an important data gap in assessing risk associated with GBE use. 

PMID- 23960168
TI  - Identification of doctors at risk of recurrent complaints: a national study of
      healthcare complaints in Australia.

PMID- 23960169
TI  - Estimating risk when zero events have been observed.

PMID- 23960171
TI  - Seroprevalence study of Equine rhinitis B virus (ERBV) in Australian weanling
      horses using serotype-specific ERBV enzyme-linked immunosorbent assays.
AB  - Respiratory infections are a major burden in the performance horse industry.
      Equine rhinitis B virus (ERBV) has been isolated from horses displaying clinical
      respiratory disease, and ERBV-neutralizing antibodies have been detected in 50
      80% of horses in reported surveys. Current ERBV isolation and detection methods
      may underestimate the number of ERBV-positive animals and do not identify
      multiple serotype infections. The aim of the current study was to develop a
      serotyping ERBV antibody-detection enzyme-linked immunosorbent assay (ELISA) and
      examine the seroprevalence of ERBV in a group of Australian weanling horses.
      ELISAs with high sensitivity and specificity were developed. The seroprevalence
      of ERBV in the weanling horses was high (74-86%); ERBV-3 antibodies were most
      prevalent (58-62%) and ERBV-2 antibodies were least prevalent (10-16%). Many
      horses were seropositive to 2 or more serotypes. All 3 serotypes of ERBV were
      detected, and concurrent positivity to multiple serotypes was common. 

PMID- 23960172
TI  - Postmortem stability of S100B in the aqueous humor of northern fur seals
      (Callorhinus ursinus).
AB  - Bycatch (accidental drowning in fishing nets) is a significant problem for some
      marine mammal species, but can be difficult to diagnose as there are no
      pathognomonic gross or histological lesions. In human medicine, biomarkers such
      as S100B are increasingly being used to investigate hypoxic-ischemic syndromes,
      but, to the authors' knowledge, studies using this marker have not been reported
      for marine mammal species. The aims of the current study were to determine
      baseline postmortem S100B levels in a pinniped species, and to determine whether
      S100B levels were stable over a postmortem interval of 48 hr. Aqueous humor,
      which is simple to collect and avoids many of the problems associated with
      postmortem collection of blood, was used as a surrogate for serum. S100B was
      detected in the aqueous humor of acute deaths (<15 min) and was stable for up to
      48 hr, with a wider variation in values at the 48-hr time interval. 

PMID- 23960170
TI  - Plasticity of basal cells during postnatal development in the rat epididymis.
AB  - Our previous study has shown that basal cells sense luminal factors by forming a
      narrow body projection that can cross epithelial tight junctions. As a first step
      toward characterizing the structural plasticity of basal cells, in this study, we
      followed their appearance and morphology in the rat epididymis and vas deferens
      (VD) during postnatal development and examined their modulation by androgens in
      adulthood. Immunofluorescence labeling for cytokeratin 5 showed that basal cells
      are absent at birth. They progressively appear in a retrograde manner from the VD
      and cauda epididymis to the initial segments during the postnatal weeks PNW1-3.
      At the onset of differentiation, basal cells are in contact with the lumen and
      their nucleus is located at the same level as that of adjacent epithelial cells.
      Basal cells then position their nucleus to the base of the epithelium, and while
      some are still in contact with the lumen, others have a 'dome-shaped' appearance.
      At PNW5-6, basal cells form a loose network at the base of the epithelium, and
      luminal-reaching basal cells are rarely detected. The arrival of spermatozoa
      during PNW7-8 did not trigger the development of projections in basal cells.
      However, cells with a narrow luminal-reaching projection began to reappear
      between PNW8 and PNW12 in the corpus and the cauda. Treatment with flutamide from
      PNW10 to PNW12 significantly reduced the number of luminal-reaching basal cell
      projections. In summary, basal cells exhibit significant structural plasticity
      during differentiation. Fewer apical-reaching projections were detected after
      flutamide treatment in adulthood, indicating the role of androgens in the luminal
      sensing function of basal cells. 

PMID- 23960173
TI  - Annealing to sequences within the primer binding site loop promotes an HIV-1 RNA
      conformation favoring RNA dimerization and packaging.
AB  - The 5' untranslated region (5' UTR) of HIV-1 genomic RNA (gRNA) includes
      structural elements that regulate reverse transcription, transcription,
      translation, tRNA(Lys3) annealing to the gRNA, and gRNA dimerization and
      packaging into viruses. It has been reported that gRNA dimerization and packaging
      are regulated by changes in the conformation of the 5'-UTR RNA. In this study, we
      show that annealing of tRNA(Lys3) or a DNA oligomer complementary to sequences
      within the primer binding site (PBS) loop of the 5' UTR enhances its dimerization
      in vitro. Structural analysis of the 5'-UTR RNA using selective 2'-hydroxyl
      acylation analyzed by primer extension (SHAPE) shows that the annealing promotes
      a conformational change of the 5' UTR that has been previously reported to favor
      gRNA dimerization and packaging into virus. The model predicted by SHAPE analysis
      is supported by antisense experiments designed to test which annealed sequences
      will promote or inhibit gRNA dimerization. Based on reports showing that the gRNA
      dimerization favors its incorporation into viruses, we tested the ability of a
      mutant gRNA unable to anneal to tRNA(Lys3) to be incorporated into virions. We
      found a ~60% decrease in mutant gRNA packaging compared with wild-type gRNA.
      Together, these data further support a model for viral assembly in which the
      initial annealing of tRNA(Lys3) to gRNA is cytoplasmic, which in turn aids in the
      promotion of gRNA dimerization and its incorporation into virions. 

PMID- 23960174
TI  - Reduction in allogeneic blood products with routine use of autotransfusion in
      open elective infrarenal abdominal aortic aneurysm repair.
AB  - BACKGROUND AND OBJECTIVES: Concern about allogeneic blood product cost and
      complications has prompted interest in blood conservation techniques.
      Intraoperative autotransfusion (IAT) is currently not used routinely by vascular
      surgeons in open elective infrareanl abdominal aortic aneurysm (AAA) repair. The
      objective of this study is to review our experience with IAT and its impact on
      blood transfusion. METHODS: We retrospectively reviewed the medical records of
      consecutive patients treated electively over a 4-year period and compared 2
      strategy related to IAT, routine use IAT (rIAT) versus on-demand IAT (oIAT).
      Outcomes measured were number of units of allogeneic red blood cells and
      autologous red blood cells transfused intraoperatively and postoperatively,
      preoperative, postoperative, and discharge hemoglobin levels; postoperative
      infections; length of postoperative intensive care stay; and length of hospital
      stay. T-independent and Fisher exact test were used. RESULTS: A total of 212
      patients were included, 38 (18%) in the rIAT and 174 (82%) in the oIAT. Groups
      were similar except for an inferior creatinine and a superior mean aneurysm
      diameter for the rIAT group. Patients in the rIAT group had a lower rate of
      transfusion (26% vs 54%, P = .002) and a lower mean number of blood unit
      transfused (0.8 vs 1.8, P = .048). These findings were still more significant for
      AAA larger than 60 mm (18% rIAT vs 62% oIAT, P = .0001). Postoperative hemoglobin
      was superior in the rIAT group (107 vs 101 g/L, P = .01). Mean postoperative
      intensive care length of stay was shorter for the rIAT group (1.1 vs 1.8 days, P
      = .01). No difference was noted for infection, mortality, or hospital length of
      stay. CONCLUSION: The rIAT reduced the exposure to allogeneic blood products by
      more than 50%, in particular for patients with AAA larger than 60 mm. These
      results support the use of rIAT for open elective infrarenal AAA repair.

PMID- 23960175
TI  - Timely completion of scientifically rigorous cancer clinical trials: an
      unfulfilled priority.

PMID- 23960176
TI  - One size does not fit all in follicular lymphoma.

PMID- 23960177
TI  - Ten years of international primary CNS lymphoma collaborative group studies.

PMID- 23960178
TI  - Can erlotinib ameliorate cisplatin-induced toxicities?

PMID- 23960179
TI  - Vertebral compression fracture after spine stereotactic body radiotherapy: a
      multi-institutional analysis with a focus on radiation dose and the spinal
      instability neoplastic score.
AB  - PURPOSE: Vertebral compression fracture (VCF) is increasingly recognized as an
      adverse event after spine stereotactic body radiotherapy (SBRT). We report a
      multi-institutional study aimed at clarifying the risk and predictive factors
      associated with VCF. PATIENTS AND METHODS: A total of 252 patients with 410
      spinal segments treated with SBRT were included. The primary outcome was the
      development of VCF (a new VCF or progression of a baseline VCF). In addition to
      various patient-, treatment-, and tumor-specific factors, the Spinal Instability
      Neoplastic Scoring (SINS) system was applied to determine predictive value.
      RESULTS: The median follow-up was 11.5 months (range, 0.03 to 113 months). The
      median and mean overall survival rates were 16 and 26 months, respectively. We
      observed 57 fractures (57 of 410, 14%), with 47% (27 of 57) new fractures and 53%
      (30 of 57) fracture progression. The median time to VCF was 2.46 months (range,
      0.03 to 43.01 months), and 65% occurred within the first 4 months. The 1- and 2
      year cumulative incidences of fracture were 12.35% and 13.49%, respectively.
      Multivariable analysis identified dose per fraction (greatest risk for >= 24 Gy v
      20 to 23 Gy v <= 19 Gy), in addition to three of the six original SINS criteria:
      baseline VCF, lytic tumor, and spinal deformity, as significant predictors of
      VCF. CONCLUSION: Caution must be observed when treating with >= 20 Gy/fraction,
      in particular, for patients with lytic tumor, spinal misalignment, and a baseline
      VCF. Frequent short-term follow-up is required, as nearly two thirds of all VCF
      occurred within the first 4 months. We also conclude that SINS may have utility
      in predicting patients at high risk of SBRT-induced VCF.

PMID- 23960180
TI  - Rituximab maintenance compared with observation after brief first-line R-FND
      chemoimmunotherapy with rituximab consolidation in patients age older than 60
      years with advanced follicular lymphoma: a phase III randomized study by the
      Fondazione Italiana Linfomi.
AB  - PURPOSE: To evaluate the efficacy of rituximab maintenance in 60- to 75-year-old
      patients with advanced follicular lymphoma responding to brief first-line
      chemoimmunotherapy followed by rituximab consolidation. PATIENTS AND METHODS: A
      total of 234 treatment-naive 60- to 75-year-old patients began chemoimmunotherapy
      with four monthly courses of rituximab, fludarabine, mitoxantrone, and
      dexamethasone (R-FND) followed by four weekly cycles of rituximab consolidation.
      Of these, 210 patients completed the planned treatment, and 202 responders were
      randomly assigned to rituximab maintenance (arm A) for 8 months, once every 2
      months for a total of four doses, or to observation (arm B). RESULTS: Median ages
      in arms A and B were 66 and 65 years, respectively. After induction and
      consolidation therapy, the overall response rate was 86%, with 69% complete
      remissions (CR). After a 42-month median follow-up from diagnosis, 3-year
      progression-free survival (PFS; the primary end point) and overall survival (OS)
      were 66% (95% CI, 59% to 72%) and 89% (95% CI, 85% to 93%), respectively. After
      randomization, 2-year PFS was 81% for rituximab maintenance versus 69% for
      observation, with a hazard ratio of 0.74 (95% CI, 0.45 to 1.21; P = .226),
      although this was not statistically significant. No differences between the two
      arms were detected for OS. Overall, the regimen was well-tolerated. The most
      frequent grade 3 to 4 toxicity was neutropenia (25% of treatment courses), with
      13 infections. Two toxic deaths (0.8%) occurred during induction treatment.
      CONCLUSION: A brief R-FND induction plus rituximab consolidation achieved
      excellent results with high CR and PFS rates, supporting the feasibility of this
      regimen in patients older than 60 years. A short rituximab maintenance did not
      achieve a statistically significant PFS improvement over observation.

PMID- 23960181
TI  - Validation of prognostic scores in post-transplantation lymphoproliferative
      disorders.

PMID- 23960182
TI  - Accelerated aging, decreased white matter integrity, and associated
      neuropsychological dysfunction 25 years after pediatric lymphoid malignancies.
AB  - PURPOSE: CNS-directed chemotherapy (CT) and cranial radiotherapy (CRT) for
      childhood acute lymphoblastic leukemia or lymphoma have various neurotoxic
      properties. This study aimed to assess their impact on the maturing brain 20 to
      30 years after diagnosis, providing a much stronger perspective on long-term
      quality of life than previous studies. PATIENTS AND METHODS: Ninety-three
      patients treated between 1978 and 1990 at various intensities, with and without
      CRT, and 49 healthy controls were assessed with magnetic resonance diffusion
      tensor imaging (DTI) and neuropsychological tests. Differences in fractional
      anisotropy (FA)-a DTI measure describing white matter (WM) microstructure-were
      analyzed by using whole brain voxel-based analysis. RESULTS: CRT-treated
      survivors demonstrated significantly decreased FA compared with controls in
      frontal, parietal, and temporal WM tracts. Trends for lower FA were seen in the
      CT-treated survivors. Decreases in FA correlated well with neuropsychological
      dysfunction. In contrast to the CT group and controls, the CRT group showed a
      steep decline of FA with age at assessment. Younger age at cranial irradiation
      and higher dosage were associated with worse outcome of WM integrity. CONCLUSION:
      CRT-treated survivors show decreased WM integrity reflected by significantly
      decreased FA and associated neuropsychological dysfunction 25 years after
      treatment, although effects of CT alone seem mild. Accelerated aging of the brain
      and increased risk of early onset dementia are suspected after CRT, but not after
      CT.

PMID- 23960184
TI  - Implications of 25-year follow-up of white matter integrity and neurocognitive
      function of childhood leukemia survivors: a wake-up call.

PMID- 23960183
TI  - How do social factors explain outcomes in non-small-cell lung cancer among
      Hispanics in California? Explaining the Hispanic paradox.
AB  - PURPOSE: Hispanics in the United States have lower age-adjusted mortality
      resulting from non-small-cell lung cancer (NSCLC) compared with non-Hispanic
      whites (NHWs). The purpose of this study was to evaluate individual, clinical,
      and neighborhood factors in survival among Hispanics with NSCLC. PATIENTS AND
      METHODS: We performed a retrospective analysis of NHWs and Hispanics with NSCLC
      between 1998 and 2007 in the California Cancer Registry (follow-up to December
      2009). Kaplan-Meier curves depict survival by nativity for Hispanics with NSCLC.
      Cox proportional hazards models estimated hazard of mortality by race with
      adjustment for individual (age, sex, marital status), clinical (histologic grade,
      surgery, irradiation, chemotherapy), and neighborhood factors (neighborhood
      socioeconomic status, ethnic enclave). RESULTS: We included 14,280 Hispanic
      patients with NSCLC. Foreign-born Hispanics had 15% decreased risk of disease
      specific mortality resulting from NSCLC compared with NHWs (hazard ratio [HR],
      0.85; 95% CI, 0.83 to 0.88) after adjustment for individual, clinical, and
      neighborhood factors. After adjustment for individual factors, compared with US
      born Hispanics, foreign-born Hispanics had 10% decreased risk of disease-specific
      mortality (HR, 0.90; 95% CI, 0.87 to 0.96). Clinical and neighborhood factors
      slightly moderated the survival benefit for foreign-born patients. A modestly
      more pronounced survival advantage was seen for foreign-born Hispanics living in
      low socioeconomic and high Hispanic enclave neighborhoods as compared with US
      born Hispanics (HR, 0.86; 95% CI, 0.81 to 0.90). CONCLUSION: Foreign-born
      Hispanics with NSCLC have a decreased risk of disease-specific mortality compared
      with NHWs and US-born Hispanics with NSCLC. Neighborhood factors slightly
      moderate this survival advantage. This survival advantage is slightly more
      pronounced in lower socioeconomic and higher Hispanic enclave neighborhoods.

PMID- 23960185
TI  - Pancreatic cancer clinical trials and accrual in the United States.
AB  - PURPOSE: Pancreatic cancer clinical trials open in the United States and their
      accrual were examined to identify opportunities to accelerate progress in the
      treatment of pancreatic cancer. METHODS: Pancreatic cancer-specific clinical
      trials open in the United States in the years 2011 and 2012 were obtained from
      the Pancreatic Cancer Action Network database. Accrual information was obtained
      from trial sponsors. RESULTS: The portfolio of pancreatic cancer clinical trials
      identified by type (adenocarcinoma or neuroendocrine), phase, disease stage, and
      treatment approach is reported. More than half of trials for patients with
      pancreatic ductal adenocarcinoma applied biologic insights to new therapeutic
      approaches, and 38% focused on optimization of radiation or chemotherapy delivery
      or regimens. In 2011, pancreatic cancer trials required total enrollment of
      11,786 patients. Actual accrual to 93.2% of trials was 1,804 patients, an
      estimated 4.57% of the patients with pancreatic cancer alive in that year. The
      greatest need was for patients with resectable cancer. Trials open in 2011
      enrolled an average of 15% of their total target accrual. Physician
      recommendations greatly influenced patients' decision to enroll or not enroll
      onto a clinical trial. Matching to a clinical trial within a 50-mile radius and
      identifying trials for recurrent/refractory disease were documented as challenges
      for patient accrual. CONCLUSION: Overall trial enrollment indicates that
      pancreatic cancer trials open in 2011 would require 6.7 years on average to
      complete accrual. These results suggest that harmonizing patient supply and
      demand for clinical trials is required to accelerate progress toward improving
      survival in pancreatic cancer.

PMID- 23960187
TI  - Difference in therapeutic response between basal and nonbasal triple-negative
      breast cancers.

PMID- 23960186
TI  - beta-Catenin mutation status and outcomes in sporadic desmoid tumors.
AB  - BACKGROUND: Mutations in the gene-encoding beta-catenin, CTNNB1, are highly
      prevalent in sporadic desmoid tumors and may predict the risk for recurrence. We
      sought to determine the prevalence of CTNNB1 mutations in a large cohort of
      sporadic desmoid tumors and to determine whether CTNNB1 mutation status
      correlates with disease outcome. METHODS: Single-base extension genotyping of the
      CTNNB1 gene was performed on 145 sporadic, paraffin-embedded desmoid tumor
      specimens. Correlation of mutation status with outcome was performed on a subset
      of 115 patients who underwent macroscopically complete surgical resection.
      RESULTS: CTNNB1 mutations were detected in 106 of 145 (73%) tumor specimens and
      in 86 of 115 (75%) specimens from patients who underwent curative-intent surgical
      resection, including discrete mutations in the following codons of CTNNB1 exon 3:
      T41A (46%), S45F (25%), S45P (1.7%), and S45C (0.9%). Desmoid tumors of the
      superficial trunk were significantly less likely to harbor CTNNB1 mutations than
      tumors located elsewhere, but none of the other examined clinicopathologic
      factors were found to be associated with CTNNB1 mutation status. At a median
      follow-up of 31 months, 5-year recurrence-free survival was slightly, although
      not statistically significantly, worse for patients with beta-catenin-mutated
      tumors than for those with wild-type tumors (58% vs. 74%, respectively). The
      specific CTNNB1 codon mutation did not correlate with the risk for recurrence.
      CONCLUSION: CTNNB1 mutations are indeed common in sporadic desmoid tumors.
      However, our study did not detect a statistically significant difference in
      recurrence risk according to either the CTNNB1 mutation status or the specific
      CTNNB1 mutation.

PMID- 23960188
TI  - DNA repair genes are selectively mutated in diffuse large B cell lymphomas.
AB  - DNA repair mechanisms are fundamental for B cell development, which relies on the
      somatic diversification of the immunoglobulin genes by V(D)J recombination,
      somatic hypermutation, and class switch recombination. Their failure is
      postulated to promote genomic instability and malignant transformation in B
      cells. By performing targeted sequencing of 73 key DNA repair genes in 29 B cell
      lymphoma samples, somatic and germline mutations were identified in various DNA
      repair pathways, mainly in diffuse large B cell lymphomas (DLBCLs). Mutations in
      mismatch repair genes (EXO1, MSH2, and MSH6) were associated with microsatellite
      instability, increased number of somatic insertions/deletions, and altered
      mutation signatures in tumors. Somatic mutations in nonhomologous end-joining
      (NHEJ) genes (DCLRE1C/ARTEMIS, PRKDC/DNA-PKcs, XRCC5/KU80, and XRCC6/KU70) were
      identified in four DLBCL tumors and cytogenetic analyses revealed that
      translocations involving the immunoglobulin-heavy chain locus occurred
      exclusively in NHEJ-mutated samples. The novel mutation targets, CHEK2 and PARP1,
      were further screened in expanded DLBCL cohorts, and somatic as well as novel and
      rare germline mutations were identified in 8 and 5% of analyzed tumors,
      respectively. By correlating defects in a subset of DNA damage response and
      repair genes with genomic instability events in tumors, we propose that these
      genes play a role in DLBCL lymphomagenesis. 

PMID- 23960189
TI  - Lung dendritic cells imprint T cell lung homing and promote lung immunity through
      the chemokine receptor CCR4.
AB  - T cell trafficking into the lung is critical for lung immunity, but the
      mechanisms that mediate T cell lung homing are not well understood. Here, we show
      that lung dendritic cells (DCs) imprint T cell lung homing, as lung DC-activated
      T cells traffic more efficiently into the lung in response to inhaled antigen and
      at homeostasis compared with T cells activated by DCs from other tissues.
      Consequently, lung DC-imprinted T cells protect against influenza more
      effectively than do gut and skin DC-imprinted T cells. Lung DCs imprint the
      expression of CCR4 on T cells, and CCR4 contributes to T cell lung imprinting.
      Lung DC-activated, CCR4-deficient T cells fail to traffic into the lung as
      efficiently and to protect against influenza as effectively as lung DC-activated,
      CCR4-sufficient T cells. Thus, lung DCs imprint T cell lung homing and promote
      lung immunity in part through CCR4. 

PMID- 23960190
TI  - Lung dendritic cells induce migration of protective T cells to the
      gastrointestinal tract.
AB  - Developing efficacious vaccines against enteric diseases is a global challenge
      that requires a better understanding of cellular recruitment dynamics at the
      mucosal surfaces. The current paradigm of T cell homing to the gastrointestinal
      (GI) tract involves the induction of alpha4beta7 and CCR9 by Peyer's patch and
      mesenteric lymph node (MLN) dendritic cells (DCs) in a retinoic acid-dependent
      manner. This paradigm, however, cannot be reconciled with reports of GI T cell
      responses after intranasal (i.n.) delivery of antigens that do not directly
      target the GI lymphoid tissue. To explore alternative pathways of cellular
      migration, we have investigated the ability of DCs from mucosal and nonmucosal
      tissues to recruit lymphocytes to the GI tract. Unexpectedly, we found that lung
      DCs, like CD103(+) MLN DCs, up-regulate the gut-homing integrin alpha4beta7 in
      vitro and in vivo, and induce T cell migration to the GI tract in vivo.
      Consistent with a role for this pathway in generating mucosal immune responses,
      lung DC targeting by i.n. immunization induced protective immunity against
      enteric challenge with a highly pathogenic strain of Salmonella. The present
      report demonstrates novel functional evidence of mucosal cross talk mediated by
      DCs, which has the potential to inform the design of novel vaccines against
      mucosal pathogens. 

PMID- 23960193
TI  - Current status of neurology in Croatia.

PMID- 23960191
TI  - IL-25 simultaneously elicits distinct populations of innate lymphoid cells and
      multipotent progenitor type 2 (MPPtype2) cells.
AB  - The predominantly epithelial cell-derived cytokines IL-25, IL-33, and thymic
      stromal lymphopoietin (TSLP) can promote CD4(+) Th2 cell-dependent immunity,
      inflammation, and tissue repair at barrier surfaces through the induction of
      multiple innate immune cell populations. IL-25 and IL-33 were previously shown to
      elicit four innate cell populations, named natural helper cells, nuocytes, innate
      type 2 helper cells, and multipotent progenitor type 2 (MPP(type2)) cells, now
      collectively termed group 2 innate lymphoid cells (ILC2). In contrast to other
      types of ILC2, MPP(type2) cells exhibit multipotent potential and do not express
      T1/ST2 or IL-7Ralpha, suggesting that MPP(type2) cells may be a distinct
      population. Here, we show that IL-33 elicits robust ILC2 responses, whereas IL-25
      predominantly promotes MPP(type2) cell responses at multiple tissue sites with
      limited effects on ILC2 responses. MPP(type2) cells were distinguished from ILC2
      by their differential developmental requirements for specific transcription
      factors, distinct genome-wide transcriptional profile, and functional potential.
      Furthermore, IL-25-induced MPP(type2) cells promoted Th2 cytokine-associated
      inflammation after depletion of ILC2. These findings indicate that IL-25
      simultaneously elicits phenotypically and functionally distinct innate lymphoid-
      and nonlymphoid-associated cell populations and implicate IL-25-elicited
      MPP(type2) cells and extramedullary hematopoiesis in the promotion of Th2
      cytokine responses at mucosal surfaces. 

PMID- 23960192
TI  - White matter hyperintensities on MRI in high-altitude U-2 pilots.
AB  - OBJECTIVE: To demonstrate that U-2 pilot occupational exposure to hypobaria leads
      to increased incidence of white matter hyperintensities (WMH) with a more uniform
      distribution throughout the brain irrespective of clinical neurologic
      decompression sickness history. METHODS: We evaluated imaging findings in 102 U-2
      pilots and 91 controls matched for age, health, and education levels. Three
      dimensional, T2-weighted, high-resolution (1-mm isotropic) imaging data were
      collected using fluid-attenuated inversion recovery sequence on a 3-tesla MRI
      scanner. Whole-brain and regional WMH volume and number were compared between
      groups using a 2-tailed Wilcoxon rank sum test. RESULTS: U-2 pilots demonstrated
      an increase in volume (394%; p = 0.004) and number (295%; p < 0.001) of WMH.
      Analysis of regional distribution demonstrated WMH more uniformly distributed
      throughout the brain in U-2 pilots compared with mainly frontal distribution in
      controls. CONCLUSION: Pilots with occupational exposure to hypobaria showed a
      significant increase in WMH lesion volume and number. Unlike the healthy controls
      with predominantly WMH in the frontal white matter, WMH in pilots were more
      uniformly distributed throughout the brain. This is consistent with our
      hypothesized pattern of damage produced by interaction between microemboli and
      cerebral tissue, leading to thrombosis, coagulation, inflammation, and/or
      activation of innate immune response, although further studies will be necessary
      to clarify the pathologic mechanisms responsible.

PMID- 23960194
TI  - Nosography of the "essential": volitional palatal tremor.

PMID- 23960195
TI  - Nonmydriatic ocular fundus photography among headache patients in an emergency
      department.

PMID- 23960196
TI  - Clinicopathologic differences among patients with behavioral variant
      frontotemporal dementia.

PMID- 23960197
TI  - Opinion and special articles: electronic media in neurology education: progress,
      promise, and pitfalls.

PMID- 23960198
TI  - Teaching NeuroImages: sciatic neuropathy after heroin abuse.

PMID- 23960199
TI  - Teaching NeuroImages: concurrent hemifacial spasm and trigeminal neuralgia due to
      vertebrobasilar dolichoectasia.

PMID- 23960201
TI  - Anticipatory planning reveals segmentation of cortical motor output during action
      observation.
AB  - It has been argued that the variation in brain activity that occurs when
      observing another person reflects a representation of actions that is
      indivisible, and which plays out in full once the intent of the actor can be
      discerned. We used transcranial magnetic stimulation to probe the excitability of
      corticospinal projections to 2 intrinsic hand muscles while motions to reach and
      grasp an object were observed. A symbolic cue either faithfully indicated the
      required final orientation of the object and thus the nature of the grasp that
      was required, or was in conflict with the movement subsequently displayed. When
      the cue was veridical, modulation of excitability was in accordance with the
      functional role of the muscles in the action observed. If however the cue had
      indicated that the alternative grasp would be required, modulation of output to
      first dorsal interosseus was consistent with the action specified, rather than
      the action observed--until the terminal phase of the motion sequence during which
      the object was seen lifted. Modulation of corticospinal output during observation
      is thus segmented--it progresses initially in accordance with the action
      anticipated, and if discrepancies are revealed by visual input, coincides
      thereafter with that of the action seen.

PMID- 23960200
TI  - Differential modifications of synaptic weights during odor rule learning:
      dynamics of interaction between the piriform cortex with lower and higher brain
      areas.
AB  - Learning of a complex olfactory discrimination (OD) task results in acquisition
      of rule learning after prolonged training. Previously, we demonstrated enhanced
      synaptic connectivity between the piriform cortex (PC) and its ascending and
      descending inputs from the olfactory bulb (OB) and orbitofrontal cortex (OFC)
      following OD rule learning. Here, using recordings of evoked field postsynaptic
      potentials in behaving animals, we examined the dynamics by which these synaptic
      pathways are modified during rule acquisition. We show profound differences in
      synaptic connectivity modulation between the 2 input sources. During rule
      acquisition, the ascending synaptic connectivity from the OB to the anterior and
      posterior PC is simultaneously enhanced. Furthermore, post-training stimulation
      of the OB enhanced learning rate dramatically. In sharp contrast, the synaptic
      input in the descending pathway from the OFC was significantly reduced until
      training completion. Once rule learning was established, the strength of synaptic
      connectivity in the 2 pathways resumed its pretraining values. We suggest that
      acquisition of olfactory rule learning requires a transient enhancement of
      ascending inputs to the PC, synchronized with a parallel decrease in the
      descending inputs. This combined short-lived modulation enables the PC network to
      reorganize in a manner that enables it to first acquire and then maintain the
      rule. 

PMID- 23960202
TI  - Effects of core auditory cortex deactivation on neuronal response to simple and
      complex acoustic signals in the contralateral anterior auditory field.
AB  - Interhemispheric communication has been implicated in various functions of
      sensory signal processing and perception. Despite ample evidence demonstrating
      this phenomenon in the visual and somatosensory systems, to date, limited
      functional assessment of transcallosal transmission during periods of acoustic
      signal exposure has hindered our understanding of the role of interhemispheric
      connections between auditory cortical fields. Consequently, the present
      investigation examines the impact of core auditory cortical field deactivation on
      response properties of contralateral anterior auditory field (AAF) neurons in the
      felis catus. Single-unit responses to simple and complex acoustic signals were
      measured across AAF before, during, and after individual and combined cooling
      deactivation of contralateral primary auditory cortex (A1) and AAF neurons. Data
      analyses revealed that on average: 1) interhemispheric projections from core
      auditory areas to contralateral AAF neurons are predominantly excitatory, 2)
      changes in response strength vary based on acoustic features, 3) A1 and AAF
      projections can modulate AAF activity differently, 4) decreases in response
      strength are not specific to particular cortical laminae, and 5) contralateral
      inputs modulate AAF neuronal response thresholds. Collectively, these
      observations demonstrate that A1 and AAF neurons predominantly modulate AAF
      response properties via excitatory projections. 

PMID- 23960203
TI  - High-expanding cortical regions in human development and evolution are related to
      higher intellectual abilities.
AB  - Cortical surface area has tremendously expanded during human evolution, and
      similar patterns of cortical expansion have been observed during childhood
      development. An intriguing hypothesis is that the high-expanding cortical regions
      also show the strongest correlations with intellectual function in humans.
      However, we do not know how the regional distribution of correlations between
      intellectual function and cortical area maps onto expansion in development and
      evolution. Here, in a sample of 1048 participants, we show that regions in which
      cortical area correlates with visuospatial reasoning abilities are generally high
      expanding in both development and evolution. Several regions in the frontal
      cortex, especially the anterior cingulate, showed high expansion in both
      development and evolution. The area of these regions was related to intellectual
      functions in humans. Low-expanding areas were not related to cognitive scores.
      These findings suggest that cortical regions involved in higher intellectual
      functions have expanded the most during development and evolution. The radial
      unit hypothesis provides a common framework for interpretation of the findings in
      the context of evolution and prenatal development, while additional cellular
      mechanisms, such as synaptogenesis, gliogenesis, dendritic arborization, and
      intracortical myelination, likely impact area expansion in later childhood. 

PMID- 23960204
TI  - Abnormal retinoid and TrkB signaling in the prefrontal cortex in mood disorders.
AB  - The prefrontal cortex shows structural and functional alterations in mood
      disorders. Retinoid signaling, brain-derived neurotrophic factor (BDNF), and its
      receptor TrkB are reported to be involved in depression. Here, we found that mRNA
      levels of key elements of retinoid signaling were significantly reduced in the
      postmortem dorsolateral prefrontal cortex/anterior cingulate cortex (ACC) from
      elderly depressed patients who did not die from suicide. Decreased mRNA levels of
      BDNF and TrkB isoforms were also found. Similar alterations were observed in rats
      subjected to chronic unpredictable mild stress. Along with neurons immunopositive
      for both retinoic acid receptor-alpha (RARalpha) and TrkB, a positive correlation
      between mRNA levels of the 2 receptors was found in the ACC of control subjects
      but not of depressed patients. In vitro studies showed that RARalpha was able to
      bind to and transactivate the TrkB promoter via a putative RA response element
      within the TrkB promoter. In conclusion, the retinoid and BDNF-TrkB signaling in
      the prefrontal cortex are compromised in mood disorders, and the transcriptional
      upregulation of TrkB by RARalpha provide a possible mechanism for their
      interaction. The retinoid signaling pathway that may activate TrkB expression
      will be an alternative novel target for BDNF-based antidepressant treatment. 

PMID- 23960205
TI  - Adaptations of motor neural structures' activity to lapses in attention.
AB  - Sustained attention is fundamental for cognition and when impaired, impacts
      negatively on important contemporary living skills. Degradation in sustained
      attention is characterized by the time-on-task (TOT) effect, which manifests as a
      gradual increase in reaction time (RT). The TOT effect is accompanied by changes
      in relative brain activity patterns in attention-related areas, most noticeably
      in the prefrontal cortex (PFC) and the right parietal areas. However, activity
      changes in task-relevant motor structures have not been confirmed to date. This
      article describes an investigation of such motor-related activity changes as
      measured with 1) the time course of corticospinal excitability (CSE) through
      single-pulse transcranial magnetic stimulation; and 2) the changes in activity of
      premotor (PMC), primary motor (M1), PFC, and right parietal areas by means of
      near-infrared spectroscopy, during a sustained attention RT task exhibiting the
      TOT effect. Our results corroborate established findings such as a significant
      increase (P < 0.05) in lateral prefrontal and right parietal areas activity after
      the emergence of the TOT effect but also reveal adaptations in the form of motor
      activity changes--in particular, a significant increase in CSE (P < 0.01) and in
      primary motor area (M1) activity (P < 0.05).

PMID- 23960206
TI  - Reduced frontal cortex efficiency is associated with lower white matter integrity
      in aging.
AB  - Increased frontal cortex activation during cognitive task performance is common
      in aging but remains poorly understood. Here we explored patterns of age-related
      frontal brain activations under multiple task performance conditions and their
      relationship to white matter (WM) microstructure. Groups of younger (N = 28) and
      older (N = 33) participants completed a task-switching paradigm while functional
      magnetic resonance imaging (fMRI) was performed, and rested while diffusion
      tensor imaging was performed. Results from fMRI analyses indicated age-related
      increases in frontal brain activations under conditions of poorer performance in
      the older group (the nonswitch and switch conditions) and for a contrast in which
      behavioral performance was equated (older group nonswitch condition vs. younger
      group switch condition). Within the older adult group, higher frontal activation
      was associated with poorer behavioral performance under all task conditions. In 2
      regions in right frontal cortex, blood oxygen level-dependent (BOLD) magnitudes
      were negatively correlated with WM integrity in tracts connecting these
      structures with other task-relevant frontoparietal and striatal regions. Our
      results link age-related declines in the efficiency of frontal cortex functioning
      with lower WM integrity in aging. 

PMID- 23960208
TI  - Perilesional treatment with chondroitinase ABC and motor training promote
      functional recovery after stroke in rats.
AB  - Ischemic stroke insults may lead to chronic functional limitations that adversely
      affect patient movements. Partial motor recovery is thought to be sustained by
      neuronal plasticity, particularly in areas close to the lesion site. It is still
      unknown if treatments acting exclusively on cortical plasticity of perilesional
      areas could result in behavioral amelioration. We tested whether enhancing
      plasticity in the ipsilesional cortex using local injections of chondroitinase
      ABC (ChABC) could promote recovery of skilled motor function in a focal cortical
      ischemia of forelimb motor cortex in rats. Using the skilled reaching test, we
      found that acute and delayed ChABC treatment induced recovery of impaired motor
      skills in treated rats. vGLUT1, vGLUT2, and vGAT staining indicated that
      functional recovery after acute ChABC treatment was associated with local plastic
      modification of the excitatory cortical circuitry positive for VGLUT2. ChABC
      effects on vGLUT2 staining were present only in rats undergoing behavioral
      training. Thus, the combination of treatments targeting the CSPG component of the
      extracellular matrix in perilesional areas and rehabilitation could be sufficient
      to enhance functional recovery from a focal stroke. 

PMID- 23960207
TI  - Systematic, cross-cortex variation in neuron numbers in rodents and primates.
AB  - Uniformity, local variability, and systematic variation in neuron numbers per
      unit of cortical surface area across species and cortical areas have been claimed
      to characterize the isocortex. Resolving these claims has been difficult, because
      species, techniques, and cortical areas vary across studies. We present a
      stereological assessment of neuron numbers in layers II-IV and V-VI per unit of
      cortical surface area across the isocortex in rodents (hamster, Mesocricetus
      auratus; agouti, Dasyprocta azarae; paca, Cuniculus paca) and primates (owl
      monkey, Aotus trivigratus; tamarin, Saguinus midas; capuchin, Cebus apella);
      these chosen to vary systematically in cortical size. The contributions of
      species, cortical areas, and techniques (stereology, "isotropic fractionator") to
      neuron estimates were assessed. Neurons per unit of cortical surface area
      increase across the rostro-caudal (RC) axis in primates (varying by a factor of
      1.64-2.13 across the rostral and caudal poles) but less in rodents (varying by a
      factor of 1.15-1.54). Layer II-IV neurons account for most of this variation.
      When integrated into the context of species variation, and this RC gradient in
      neuron numbers, conflicts between studies can be accounted for. The RC variation
      in isocortical neurons in adulthood mirrors the gradients in neurogenesis
      duration in development. 

PMID- 23960209
TI  - A segregated neural pathway for prefrontal top-down control of tactile
      discrimination.
AB  - It has proven difficult to separate functional areas in the prefrontal cortex
      (PFC), an area implicated in attention, memory, and distraction handling. Here,
      we assessed in healthy human subjects whether PFC subareas have different roles
      in top-down regulation of sensory functions by determining how the neural links
      between the PFC and the primary somatosensory cortex (S1) modulate tactile
      perceptions. Anatomical connections between the S1 representation area of the
      cutaneous test site and the PFC were determined using probabilistic tractography.
      Single-pulse navigated transcranial magnetic stimulation of the middle frontal
      gyrus-S1 link, but not that of the superior frontal gyrus-S1 link, impaired the
      ability to discriminate between single and twin tactile pulses. The impairment
      occurred within a restricted time window and skin area. The spatially and
      temporally organized top-down control of tactile discrimination through a
      segregated PFC-S1 pathway suggests functional specialization of PFC subareas in
      fine-tuned regulation of information processing. 

PMID- 23960210
TI  - Human von Economo neurons express transcription factors associated with Layer V
      subcerebral projection neurons.
AB  - The von Economo neurons (VENs) are large bipolar Layer V projection neurons found
      chiefly in the anterior cingulate and frontoinsular cortices. Although VENs have
      been linked to prevalent illnesses such as frontotemporal dementia, autism, and
      schizophrenia, little is known about VEN identity, including their major
      projection targets. Here, we undertook a developmental transcription factor
      expression study, focusing on markers associated with specific classes of Layer V
      projection neurons. Using mRNA in situ hybridization, we found that VENs
      prominently express FEZF2 and CTIP2, transcription factors that regulate the fate
      and differentiation of subcerebral projection neurons, in humans aged 3 months to
      65 years. In contrast, few VENs expressed markers associated with callosal or
      corticothalamic projections. These findings suggest that VENs may represent a
      specialized Layer V projection neuron for linking cortical autonomic control
      sites to brainstem or spinal cord regions. 

PMID- 23960212
TI  - CB1 and CB2 cannabinoid receptor antagonists prevent minocycline-induced
      neuroprotection following traumatic brain injury in mice.
AB  - Traumatic brain injury (TBI) and its consequences represent one of the leading
      causes of death in young adults. This lesion mediates glial activation and the
      release of harmful molecules and causes brain edema, axonal injury, and
      functional impairment. Since glial activation plays a key role in the development
      of this damage, it seems that controlling it could be beneficial and could lead
      to neuroprotective effects. Recent studies show that minocycline suppresses
      microglial activation, reduces the lesion volume, and decreases TBI-induced
      locomotor hyperactivity up to 3 months. The endocannabinoid system (ECS) plays an
      important role in reparative mechanisms and inflammation under pathological
      situations by controlling some mechanisms that are shared with minocycline
      pathways. We hypothesized that the ECS could be involved in the neuroprotective
      effects of minocycline. To address this hypothesis, we used a murine TBI model in
      combination with selective CB1 and CB2 receptor antagonists (AM251 and AM630,
      respectively). The results provided the first evidence for the involvement of ECS
      in the neuroprotective action of minocycline on brain edema, neurological
      impairment, diffuse axonal injury, and microglial activation, since all these
      effects were prevented by the CB1 and CB2 receptor antagonists. 

PMID- 23960213
TI  - Time- but not sleep-dependent consolidation of tDCS-enhanced visuomotor skills.
AB  - Consolidation of motor skills after training can occur in a time- or sleep
      dependent fashion. Recent studies revealed time-dependent consolidation as a
      common feature of visuomotor tasks. We have previously shown that anodal
      transcranial direct current stimulation (tDCS) in combination with repeated motor
      training benefits consolidation by the induction of offline skill gains in a
      complex visuomotor task, preventing the regular occurrence of skill loss between
      days. Here, we asked 2 questions: What is the time course of consolidation
      between days for this task and do exogenously induced offline gains develop as a
      function of time or overnight sleep? We found that both the development of
      offline skill loss in sham-stimulated subjects and offline skill gains induced by
      anodal tDCS critically depend on the passage of time after training, but not on
      overnight sleep. These findings support the view that tDCS interacts directly
      with the physiological consolidation process. However, in a control experiment,
      anodal tDCS applied after the training did not induce skill gains, implying that
      coapplication of tDCS and training is required to induce offline skill gains,
      pointing to the initiation of consolidation already during training. 

PMID- 23960211
TI  - Asymmetry of the endogenous opioid system in the human anterior cingulate: a
      putative molecular basis for lateralization of emotions and pain.
AB  - Lateralization of the processing of positive and negative emotions and pain
      suggests an asymmetric distribution of the neurotransmitter systems regulating
      these functions between the left and right brain hemispheres. By virtue of their
      ability to selectively mediate euphoria, dysphoria, and pain, the MU-, delta-,
      and kappa-opioid receptors and their endogenous ligands may subserve these
      lateralized functions. We addressed this hypothesis by comparing the levels of
      the opioid receptors and peptides in the left and right anterior cingulate cortex
      (ACC), a key area for emotion and pain processing. Opioid mRNAs and peptides and
      5 "classical" neurotransmitters were analyzed in postmortem tissues from 20 human
      subjects. Leu-enkephalin-Arg (LER) and Met-enkephalin-Arg-Phe, preferential delta
      /MU- and kappa-/MU-opioid agonists, demonstrated marked lateralization to the
      left and right ACC, respectively. Dynorphin B (Dyn B) strongly correlated with
      LER in the left, but not in the right ACC suggesting different mechanisms of the
      conversion of this kappa-opioid agonist to delta-/MU-opioid ligand in the 2
      hemispheres; in the right ACC, Dyn B may be cleaved by PACE4, a proprotein
      convertase regulating left-right asymmetry formation. These findings suggest that
      region-specific lateralization of neuronal networks expressing opioid peptides
      underlies in part lateralization of higher functions, including positive and
      negative emotions and pain in the human brain. 

PMID- 23960214
TI  - Sinoatrial node reentry in a canine chronic left ventricular infarct model: role
      of intranodal fibrosis and heterogeneity of refractoriness.
AB  - BACKGROUND: Reentrant arrhythmias involving the sinoatrial node (SAN), namely SAN
      reentry, remain one of the most intriguing enigmas of cardiac electrophysiology.
      The goal of the present study was to elucidate the mechanism of SAN micro-reentry
      in canine hearts with post-myocardial infarction (MI) structural remodeling.
      METHODS AND RESULTS: In vivo, Holter monitoring revealed ventricular arrhythmias
      and SAN dysfunctions in post-left ventricular MI (6-15 weeks) dogs (n=5) compared
      with control dogs (n=4). In vitro, high-resolution near-infrared optical mapping
      of intramural SAN activation was performed in coronary perfused atrial
      preparations from MI (n=5) and controls (n=4). Both SAN macro- (slow-fast; 16-28
      mm) and micro-reentry (1-3 mm) were observed in 60% of the MI preparations during
      moderate autonomic stimulation (acetylcholine [0.1 umol/L] or isoproterenol [0.01
      0.1 umol/L]) after termination of atrial tachypacing (5-8 Hz), a finding not seen
      in controls. The autonomic stimulation induced heterogeneous changes in the SAN
      refractoriness; thus, competing atrial or SAN pacemaker waves could produce
      unidirectional blocks and initiate intranodal micro-reentry. The micro-reentry
      pivot waves were anchored to the longitudinal block region and produced both
      tachycardia and paradoxical bradycardia (due to exit block), despite an atrial
      ECG morphology identical to regular sinus rhythm. Intranodal longitudinal
      conduction blocks coincided with interstitial fibrosis strands that were
      exaggerated in the MI SAN pacemaker complex (fibrosis density: 37+/-7% MI versus
      23+/-6% control; P<0.001). CONCLUSIONS: Both tachy- and brady-arrhythmias can
      result from SAN micro-reentry. Postinfarction remodeling, including increased
      intranodal fibrosis and heterogeneity of refractoriness, provides substrates for
      SAN reentry.

PMID- 23960216
TI  - Stochastic description of delayed systems.
AB  - We study general stochastic birth and death processes including delay. We develop
      several approaches for the analytical treatment of these non-Markovian systems,
      valid, not only for constant delays, but also for stochastic delays with
      arbitrary probability distributions. The interplay between stochasticity and
      delay and, in particular, the effects of delay in the fluctuations and time
      correlations are discussed. 

PMID- 23960215
TI  - Atherosclerotic plaque composition and classification identified by coronary
      computed tomography: assessment of computed tomography-generated plaque maps
      compared with virtual histology intravascular ultrasound and histology.
AB  - BACKGROUND: Computed tomography (CT) is used routinely for coronary angiography,
      and higher-risk features of plaques can also be identified. However, the ability
      of CT to discriminate individual plaque components and classify plaques according
      to accepted histological definitions is unknown. METHODS AND RESULTS: We first
      determined CT attenuation ranges for individual plaque components using combined
      in vivo CT coregistered with virtual histology intravascular ultrasound (VH-IVUS)
      in 108 plaques from 57 patients. Comparison with contrast attenuation created
      plaque/contrast attenuation ratios that were significantly different for each
      component. In a separate validation cohort of 47 patients, these Plaque Maps
      correlated significantly with VH-IVUS-determined plaque component volumes
      (necrotic core: r=0.41, P=0.002; fibrous plaque: r=0.54, P<0.001; calcified
      plaque: r=0.59, P<0.001; total plaque: r=0.62, P<0.001). We also assessed VH-IVUS
      and CT Plaque Maps against coregistered histology in 72 (VH-IVUS) and 87 (CT)
      segments from 8 postmortem coronary arteries. The diagnostic accuracy of CT to
      detect calcified plaque (83% versus 92%), necrotic core (80% versus 65%), and
      fibroatheroma (80% versus 79%) was comparable with VH-IVUS. However, although VH
      IVUS could identify thin-cap fibroatheromas (TCFA) with a diagnostic accuracy of
      between 74% and 82% (depending on the TCFA definition used), the spatial
      resolution of CT prevented direct identification of TCFA. CONCLUSIONS: CT-derived
      Plaque Maps based on contrast-adjusted attenuation ranges can define individual
      plaque components with a similar accuracy to VH-IVUS ex vivo. However, coronary
      CT Plaque Maps could not reliably classify plaques and identify TCFA, such that
      high-risk plaques may be misclassified or overlooked.

PMID- 23960217
TI  - Slow-fast dynamics of a time-delayed electro-optic oscillator.
AB  - Square-wave oscillations exhibiting different plateau lengths have been observed
      experimentally by investigating an electro-optic oscillator. In a previous study,
      we analysed the model delay differential equations and determined an asymptotic
      approximation of the two plateaus. In this paper, we concentrate on the fast
      transition layers between plateaus and show how they contribute to the total
      period. We also investigate the bifurcation diagram of all possible stable
      solutions. We show that the square waves emerge from the first Hopf bifurcation
      of the basic steady state and that they may coexist with stable low-frequency
      periodic oscillations for the same value of the control parameter. 

PMID- 23960218
TI  - The consensus problem in networks with transmission delays.
AB  - We study discrete- and continuous-time consensus problems on networks in the
      presence of distributed time delays. We focus on information transmission delays,
      as opposed to information processing delays, so that each node of the network
      compares its current state with the past states of its neighbours. We consider
      directed and weighted networks where the connection structure is described by a
      normalized Laplacian matrix and show that consensus is achieved if and only if
      the underlying graph contains a directed spanning tree. This statement holds
      independently of the transmission delays, which is in contrast to the case of
      processing delays. Furthermore, we calculate the consensus value explicitly, and
      show that it is determined by the history of the system over an interval of time,
      unlike the case of processing delays where the consensus value depends only on
      the initial state of the system at time zero. This provides the consensus
      algorithm with improved robustness against noise. 

PMID- 23960219
TI  - Chaos in networks with time-delayed couplings.
AB  - Networks of nonlinear units coupled by time-delayed signals can show chaos. In
      the limit of long delay times, chaos appears in two ways: strong and weak,
      depending on how the maximal Lyapunov exponent scales with the delay time. Only
      for weak chaos, a network can synchronize completely, without time shift. The
      conditions for strong and weak chaos and synchronization in networks with
      multiple delay times are investigated. 

PMID- 23960220
TI  - Amplitude death in networks of delay-coupled delay oscillators.
AB  - Amplitude death is a dynamical phenomenon in which a network of oscillators
      settles to a stable state as a result of coupling. Here, we study amplitude death
      in a generalized model of delay-coupled delay oscillators. We derive analytical
      results for degree homogeneous networks which show that amplitude death is
      governed by certain eigenvalues of the network's adjacency matrix. In particular,
      these results demonstrate that in delay-coupled delay oscillators amplitude death
      can occur for arbitrarily large coupling strength k. In this limit, we find a
      region of amplitude death which already occurs at small coupling delays that
      scale with 1/k. We show numerically that these results remain valid in random
      networks with heterogeneous degree distribution. 

PMID- 23960221
TI  - An odd-number limitation of extended time-delayed feedback control in autonomous
      systems.
AB  - We propose a necessary condition for the successful stabilization of a periodic
      orbit, using the extended version of time-delayed feedback control. This
      condition depends on the number of real Floquet multipliers larger than unity and
      is therefore related to the well-known odd-number limitation in non-autonomous
      systems. We show that the period of the orbit that is induced by mismatching the
      delay time of the control scheme and the period of the uncontrolled orbit plays
      an important role in the formulation of the odd-number limitation in the
      autonomous case. 

PMID- 23960222
TI  - Complexity in electro-optic delay dynamics: modelling, design and applications.
AB  - Nonlinear delay dynamics have found during the last 30 years a particularly
      prolific exploration area in the field of photonic systems. Besides the popular
      external cavity laser diode set-ups, we focus in this article on another
      experimental realization involving electro-optic (EO) feedback loops, with delay.
      This approach has strongly evolved with the important technological progress made
      on broadband photonic and optoelectronic devices dedicated to high-speed optical
      telecommunications. The complex dynamical systems performed by nonlinear delayed
      EO feedback loop architectures were designed and explored within a huge range of
      operating parameters. Thanks to the availability of high-performance photonic
      devices, these EO delay dynamics led also to many successful, efficient and
      diverse applications, beyond the many fundamental questions raised from the
      observation of experimental behaviours. Their chaotic motion allowed for a
      physical layer encryption method to secure optical data, with a demonstrated
      capability to operate at the typical speed of modern optical telecommunications.
      Microwave limit cycles generated in similar EO delay oscillators showed
      significantly improved spectral purity thanks to the use of a very long fibre
      delay line. Last but not least, a novel brain inspired computational principle
      has been recently implemented physically in photonics for the first time, again
      on the basis of an EO delay dynamical system. In this latter emerging
      application, the computed result is obtained by a proper 'read-out' of the
      complex nonlinear transients emerging from a fixed point, the transient being
      issued by the injection of the information signal to be processed. 

PMID- 23960223
TI  - Dynamics, control and information in delay-coupled systems: an overview.

PMID- 23960224
TI  - Amplitude and phase dynamics in oscillators with distributed-delay coupling.
AB  - This paper studies the effects of distributed-delay coupling on the dynamics in a
      system of non-identical coupled Stuart-Landau oscillators. For uniform and gamma
      delay distribution kernels, the conditions for amplitude death are obtained in
      terms of average frequency, frequency detuning and the parameters of the
      coupling, including coupling strength and phase, as well as the mean time delay
      and the width of the delay distribution. To gain further insights into the
      dynamics inside amplitude death regions, the eigenvalues of the corresponding
      characteristic equations are computed numerically. Oscillatory dynamics of the
      system is also investigated, using amplitude and phase representation. Various
      branches of phase-locked solutions are identified, and their stability is
      analysed for different types of delay distributions. 

PMID- 23960225
TI  - Feedback control of unstable periodic orbits in equivariant Hopf bifurcation
      problems.
AB  - Symmetry-breaking Hopf bifurcation problems arise naturally in studies of pattern
      formation. These equivariant Hopf bifurcations may generically result in multiple
      solution branches bifurcating simultaneously from a fully symmetric equilibrium
      state. The equivariant Hopf bifurcation theorem classifies these solution
      branches in terms of their symmetries, which may involve a combination of spatial
      transformations and temporal shifts. In this paper, we exploit these spatio
      temporal symmetries to design non-invasive feedback controls to select and
      stabilize a targeted solution branch, in the event that it bifurcates unstably.
      The approach is an extension of the Pyragas delayed feedback method, as it was
      developed for the generic subcritical Hopf bifurcation problem. Restrictions on
      the types of groups where the proposed method works are given. After addition of
      the appropriately optimized feedback term, we are able to compute the stability
      of the targeted solution using standard bifurcation theory, and give an account
      of the parameter regimes in which stabilization is possible. We conclude by
      demonstrating our results with a numerical example involving symmetrically
      coupled identical nonlinear oscillators. 

PMID- 23960226
TI  - Delayed feedback control in quantum transport.
AB  - Feedback control in quantum transport has been predicted to give rise to several
      interesting effects, among them quantum state stabilization and the realization
      of a mesoscopic Maxwell's daemon. These results were derived under the assumption
      that control operations on the system are affected instantaneously after the
      measurement of electronic jumps through it. In this contribution, I describe how
      to include a delay between detection and control operation in the master equation
      theory of feedback-controlled quantum transport. I investigate the consequences
      of delay for the state stabilization and Maxwell's daemon schemes. Furthermore, I
      describe how delay can be used as a tool to probe coherent oscillations of
      electrons within a transport system and how this formalism can be used to model
      finite detector bandwidth. 

PMID- 23960227
TI  - The dynamics of genetic control in the cell: the good and bad of being late.
AB  - The expression of genes in the cell is controlled by a complex interaction
      network involving proteins, RNA and DNA. The molecular events associated with the
      nodes of such a network take place on a variety of time scales, and thus cannot
      be regarded as instantaneous. In many cases, the cell is robust with respect to
      the delay in gene expression control, behaving as if it were instantaneous.
      However, there are specific cases in which delay gives rise to temporal
      oscillations. This is the case, for example, of the expression of tumour
      suppressor protein p53, of protein Hes1, involved in the differentiation of stem
      cells, of NFkB and Wnt, in which case delay arises implicitly from the structure
      of the associated network. By means of delay rate equations, we study the
      kinetics of small regulatory networks, emphasizing the role of delay in an
      evolutionary context. These models suggest that oscillations are a typical
      outcome of the dynamics of regulatory networks, and evolution has to work to
      avoid them when not required (and not vice versa). 

PMID- 23960228
TI  - Bifurcation analysis of delay-induced patterns in a ring of Hodgkin-Huxley
      neurons.
AB  - Rings of delay-coupled neurons possess a striking capability to produce various
      stable spiking patterns. In order to reveal the mechanisms of their appearance,
      we present a bifurcation analysis of the Hodgkin-Huxley (HH) system with delayed
      feedback as well as a closed loop of HH neurons. We consider mainly the effects
      of external currents and communication delays. It is shown that typically
      periodic patterns of different spatial form (wavenumber) appear via Hopf
      bifurcations as the external current or time delay changes. The Hopf bifurcations
      are shown to occur in relatively narrow regions of the external current values,
      which are independent of the delays. Additional patterns, which have the same
      wavenumbers as the existing ones, appear via saddle-node bifurcations of limit
      cycles. The obtained bifurcation diagrams are evidence for the important role of
      communication delays for the emergence of multiple coexistent spiking patterns.
      The effects of a short-cut, which destroys the rotational symmetry of the ring,
      are also briefly discussed. 

PMID- 23960229
TI  - Two-parameter study of square-wave switching dynamics in orthogonally delay
      coupled semiconductor lasers.
AB  - We perform a detailed numerical analysis of square-wave (SW) polarization
      switching in two semiconductor lasers with time-delayed, orthogonal mutual
      coupling. An in-depth mapping of the dynamics in the two-parameter plane coupling
      strength versus frequency detuning shows that stable SWs occur in narrow
      parameter regions that are localized close to the boundary of stability of the
      pure-mode solution. In this steady state, the two coupled lasers emit orthogonal
      polarizations. We also show that there are various types of SW forms and that
      stable switching does not need the inclusion of noise or nonlinear gain in the
      model. As these narrow regions of deterministic and stable SWs occur for quite
      different combinations of parameters, they could potentially explain the
      waveforms that have been observed experimentally. However, on the other hand,
      these regions are narrow enough to be in fact considered as experimentally
      unreachable. Therefore, our results indicate that further experimental
      statistical studies are needed in order to distinguish deterministic and
      stationary square waveforms from long transients because of noise. 

PMID- 23960230
TI  - Delayed feedback control of three diffusively coupled Stuart-Landau oscillators:
      a case study in equivariant Hopf bifurcation.
AB  - The modest aim of this case study is the non-invasive and pattern-selective
      stabilization of discrete rotating waves ('ponies on a merry-go-round') in a
      triangle of diffusively coupled Stuart-Landau oscillators. We work in a setting
      of symmetry-breaking equivariant Hopf bifurcation. Stabilization is achieved by
      delayed feedback control of Pyragas type, adapted to the selected spatio-temporal
      symmetry pattern. Pyragas controllability depends on the parameters for the
      diffusion coupling, the complex control amplitude and phase, the uncontrolled
      super-/sub-criticality of the individual oscillators and their soft/hard spring
      characteristics. We mathematically derive explicit conditions for Pyragas control
      to succeed. 

PMID- 23960231
TI  - Expression of leukotriene B4 receptor-1 on CD8+ T cells is required for their
      migration into tumors to elicit effective antitumor immunity.
AB  - Leukotriene B4 (LTB4) receptor (BLT)1 is expressed on variety of immune cells and
      has been implicated as a mediator of diverse inflammatory diseases. However,
      whether biological responses initiated via this receptor generate tumor-promoting
      inflammation or antitumor immunity remains unexplored. In this study, we
      investigated the role of BLT1 in antitumor immunity using syngeneic TC-1 cervical
      cancer model, and observed accelerated tumor growth and reduced survival in BLT1
      /- mice compared with BLT1+/+ mice. Analysis of the tumor infiltrates by flow
      cytometry and confocal microscopy revealed a significant decrease in effector
      immune cells, most notably, CD8+ T cells and NK cells in the tumors of the BLT1-/
      mice. Gene expression profiling confirmed the dramatic decrease of IFN-gamma,
      granzyme B, and IL-2 in tumors growing in BLT1-/- mice. Furthermore, depletion of
      CD8+ T cells enhanced the tumor growth in BLT1+/+ but not in BLT1-/- mice.
      However, similar levels of Ag-dependent CD8+ T cell-mediated killing activity
      were observed in spleens of BLT1+/+ and BLT1-/- mice. Adoptive transfer of CD8+ T
      cells from tumor-bearing BLT1+/+ but not BLT1-/- mice significantly reduced tumor
      growth and increased the survival of Rag2-/- mice. Although the homeostatic
      proliferation and expression profiles of other chemokine receptors of adoptively
      transferred BLT1+/+ and BLT1-/- CD8+ T cells appears to be similar, BLT1+/+ T
      lymphocytes entered the tumors in greater numbers. These results suggest that
      BLT1 expression on CD8+ T cells plays an important role in their trafficking to
      tumors.

PMID- 23960233
TI  - B cells, dendritic cells, and macrophages are required to induce an autoreactive
      CD4 helper T cell response in experimental epidermolysis bullosa acquisita.
AB  - In autoimmune bullous dermatoses (AIBD), autoantibodies induce blisters on skin
      or mucous membranes, or both. Mechanisms of continued autoantibody production and
      blistering have been well characterized using AIBD animal models. Mechanisms
      leading to the initial autoantibody production, however, have not been
      investigated in detail. Epidermolysis bullosa acquisita (EBA) is an AIBD
      associated with autoantibodies to type VII collagen (COL7). The majority of EBA
      patients' sera recognize the noncollagenous domain 1, including the von
      Willebrand factor A-like domain 2 (vWFA2). In experimental EBA induced by
      immunization with GST-COL7, disease manifestation depended on the genetic
      background, a Th1 polarization, and the GST-tag. In this model, nude mice neither
      produced autoantibodies nor blisters. It has remained uncertain which APC and T
      cell subsets are required for EBA induction. We established a novel EBA model by
      immunization with vWFA2 fused to intein (lacking the GST-tag). All tested mouse
      strains developed autoantibodies, but blisters were exclusively observed in mice
      carrying H2s. In immunized mice, CD4 T cells specific for vWFA2 were detected,
      and their induction required presence of B cells, dendritic cells, and
      macrophages. Anti-vWFA2 autoantibodies located at the lamina densa bound to the
      dermal side of salt-split skin and induced blisters when transferred into healthy
      mice. Absence of CD8 T cells at time of immunization had no effect, whereas
      depletion of CD4 T cells during the same time period delayed autoantibody
      production and blisters. Collectively, we demonstrate the pathogenic relevance of
      Abs targeting the vWFA2 domain of COL7 and show the requirement of APC-induced
      CD4 T cells to induce experimental EBA. 

PMID- 23960232
TI  - IL-4 and retinoic acid synergistically induce regulatory dendritic cells
      expressing Aldh1a2.
AB  - Although activated inflammatory monocytes (IMCs) and inflammatory dendritic cells
      (IDCs) are potent T cell suppressors, nonactivated IMCs and IDCs promote T cell
      activation and Th1/Th17 cell differentiation. In this study, we investigated how
      to reduce the proinflammatory properties of IMCs and IDCs and further convert
      them into immune regulatory dendritic cells (DCs). We found that IL-4 and
      retinoic acid (RA) cotreatment of GM-CSF-differentiated IDCs synergistically
      induced the expression of aldehyde dehydrogenase family 1, subfamily A2, a rate
      limiting enzyme for RA synthesis in DCs. IL-4 plus RA-treated IDCs upregulated
      CD103 expression and markedly reduced the production of proinflammatory cytokines
      upon activation. IL-4 plus RA-treated IDCs strongly induced CD4+Foxp3+ regulatory
      T cell differentiation and suppressed Th1 and Th17 differentiation.
      Mechanistically, the transcription factors Stat6 and RA receptor beta play
      important roles in aldehyde dehydrogenase family 1, subfamily A2, induction. In
      addition, IL-4 and RA signaling pathways interact closely to enhance the
      regulatory function of treated DCs. Adoptive transfer of IL-4 plus RA-treated DCs
      significantly increased regulatory T cell frequency in vivo. Direct treatment
      with IL-4 and RA also markedly suppressed actively induced experimental
      autoimmune encephalomyelitis. Our data demonstrate the synergistic effect of IL-4
      and RA in inducing a regulatory phenotype in IDCs, providing a potential
      treatment strategy for autoimmune diseases.

PMID- 23960234
TI  - Morphine prevents lipopolysaccharide-induced TNF secretion in mast cells blocking
      IkappaB kinase activation and SNAP-23 phosphorylation: correlation with the
      formation of a beta-arrestin/TRAF6 complex.
AB  - We have previously shown that morphine pretreatment inhibits mast cell-dependent
      TNF production after LPS injection in the murine peritoneal cavity. In this
      study, we used bone marrow-derived mast cells (BMMCs) to investigate the
      molecular mechanisms of that inhibition. We found that morphine prevented LPS
      induced TNF secretion in these cells. The observed inhibition was not due to
      morphine-induced TLR4 internalization and it was related to the blockage of
      preformed TNF secretion. LPS-induced TNF exocytosis in BMMCs was dependent on
      tetanus toxin-insensitive vesicle-associated membrane proteins and calcium
      mobilization, as well as PI3K, MAPK, and IkappaB kinase (IKK) activation. TNF
      secretion was also associated to the phosphorylation of synaptosomal-associated
      protein 23 (SNAP-23), which was found forming a complex with IKK in LPS-activated
      BMMCs. Morphine pretreatment prevented TLR4-dependent ERK and IKK
      phosphorylation. Analyzing the signaling events upstream of IKK activation, we
      found diminished TGF-beta-activated kinase 1 (TAK1) phosphorylation and TNFR
      associated factor (TRAF) 6 ubiquitination in BMMCs pretreated with morphine and
      stimulated with LPS. Morphine pretreatment provoked a marked increase in the
      formation of a molecular complex composed of TRAF6 and beta-arrestin-2. Naloxone
      and a combination of MU and delta opioid receptor antagonists prevented morphine
      inhibitory actions. In conclusion, our results show that activation of MU and
      delta opioid receptors with morphine suppresses TLR4-induced TNF release in mast
      cells, preventing the IKK-dependent phosphorylation of SNAP-23, which is
      necessary for TNF exocytosis, and this inhibition correlates with the formation
      of a beta-arrestin-2/TRAF6 complex. To our knowledge, these findings constitute
      the first evidence of molecular crosstalk between opioid receptors and the TLR4
      signal transduction system in mast cells. 

PMID- 23960235
TI  - Enhanced TCR footprint by a novel glycolipid increases NKT-dependent tumor
      protection.
AB  - NKT cells, a unique type of regulatory T cells, respond to structurally diverse
      glycolipids presented by CD1d. Although it was previously thought that
      recognition of glycolipids such as alpha-galactosylceramide (alpha-GalCer) by the
      NKT cell TCR (NKTCR) obeys a key-lock principle, it is now clear this interaction
      is much more flexible. In this article, we report the structure-function analysis
      of a series of novel 6''-OH analogs of alpha-GalCer with more potent antitumor
      characteristics. Surprisingly, one of the novel carbamate analogs, alpha-GalCer
      6''-(pyridin-4-yl)carbamate, formed novel interactions with the NKTCR. This
      interaction was associated with an extremely high level of Th1 polarization and
      superior antitumor responses. These data highlight the in vivo relevance of
      adding aromatic moieties to the 6''-OH position of the sugar and additionally
      show that judiciously chosen linkers are a promising strategy to generate strong
      Th1-polarizing glycolipids through increased binding either to CD1d or to NKTCR. 

PMID- 23960237
TI  - Hepatitis C virus-infected cells downregulate NKp30 and inhibit ex vivo NK cell
      functions.
AB  - Hepatitis C virus (HCV) successfully evades the immune system and establishes
      chronic infection in ~80% of cases. Immune evasion may involve modulating NK cell
      functions. Therefore, we developed a short-term assay to assess immediate effects
      of HCV-infected cells on ex vivo NK cytotoxicity and cytokine production. Natural
      cytotoxicity, Ab-dependent cell-mediated cytotoxicity, IFN-gamma production, and
      TNF-alpha production were all significantly inhibited by short-term direct
      exposure to HCV-infected hepatoma-derived Huh-7.5 cells. Inhibition required cell
      to-cell contact and increased together with multiplicity of infection and HCV
      protein levels. Blocking potential interaction between HCV E2 and NK CD81 did not
      abrogate NK cell inhibition mediated by HCV-infected cells. We observed no change
      in expression levels of NKG2D, NKG2A, NKp46, or CD16 on NK cells exposed to HCV
      infected Huh-7.5 cells for 5 h or of human histocompatibility-linked leukocyte Ag
      E on HCV-infected compared with uninfected Huh-7.5 cells. Inhibition of ex vivo
      NK functions did correspond with reduced surface expression of the natural
      cytotoxicity receptor NKp30, and downregulation of NKp30 was functionally
      reflected in reduced anti-NKp30 redirected lysis of P815 cells. Infection of Huh
      7.5 cells with HCV JFH1(T) increased surface binding of an NKp30-IgG1 Fcgamma
      fusion protein, suggesting upregulation of an antagonistic NKp30 ligand on HCV
      infected cells. Our assay demonstrates rapid inhibition of critical NK cell
      functions by HCV-infected cells. Similar localized effects in vivo may contribute
      to establishment of chronic HCV infection and associated phenotypic and
      functional changes in the NK population.

PMID- 23960236
TI  - MiR-210 is induced by Oct-2, regulates B cells, and inhibits autoantibody
      production.
AB  - MicroRNAs (MiRs) are small, noncoding RNAs that regulate gene expression
      posttranscriptionally. In this study, we show that MiR-210 is induced by Oct-2, a
      key transcriptional mediator of B cell activation. Germline deletion of MiR-210
      results in the development of autoantibodies from 5 mo of age. Overexpression of
      MiR-210 in vivo resulted in cell autonomous expansion of the B1 lineage and
      impaired fitness of B2 cells. Mice overexpressing MiR-210 exhibited impaired
      class-switched Ab responses, a finding confirmed in wild-type B cells transfected
      with a MiR-210 mimic. In vitro studies demonstrated defects in cellular
      proliferation and cell cycle entry, which were consistent with the transcriptomic
      analysis demonstrating downregulation of genes involved in cellular proliferation
      and B cell activation. These findings indicate that Oct-2 induction of MiR-210
      provides a novel inhibitory mechanism for the control of B cells and autoantibody
      production. 

PMID- 23960238
TI  - Cutting edge: Ly49C/I- neonatal NK cells predispose newborns to autoimmune
      ovarian disease induced by maternal autoantibody.
AB  - NK cells are critical in immune responses against pathogens. However, their role
      in autoimmunity is still controversial. In this study, we demonstrate that
      neonatal NK cells render newborns more susceptible to neonatal autoimmunity
      induced by maternal autoantibodies (neonatal autoimmune ovarian disease); thus,
      neonatal but not adult NK cells are pathogenic after transfer into NK cell
      deficient pups. The inhibitory receptors Ly49C/I are expressed in ~5% of neonatal
      and ~50% of adult NK cells. In this study, we show that the presence of Ly49C/I+
      adult NK cells inhibits neonatal autoimmune ovarian disease induction. Thus, the
      ontogenetic regulation of Ly49C/I expression determines the propensity to
      autoantibody-induced autoimmunity. In summary, this study provides definitive
      evidence of a pathogenic role of NK cells in neonatal autoimmunity and also
      elucidates a novel mechanism by which neonatal NK cells render newborns more
      susceptible to autoantibody-induced autoimmunity.

PMID- 23960239
TI  - The interdependent, overlapping, and differential roles of type I and II IFNs in
      the pathogenesis of experimental autoimmune encephalomyelitis.
AB  - Type I IFNs (IFN-alpha and IFN-beta) and type II IFN (IFN-gamma) mediate both
      regulation and inflammation in multiple sclerosis, neuromyelitis optica, and in
      experimental autoimmune encephalomyelitis (EAE). However, the underlying
      mechanism for these Janus-like activities of type I and II IFNs in
      neuroinflammation remains unclear. Although endogenous type I IFN signaling
      provides a protective response in neuroinflammation, we find that when IFN-gamma
      signaling is ablated, type I IFNs drive inflammation, resulting in exacerbated
      EAE. IFN-gamma has a disease stage-specific opposing function in EAE. Treatment
      of mice with IFN-gamma during the initiation phase of EAE leads to enhanced
      severity of disease. In contrast, IFN-gamma treatment during the effector phase
      attenuated disease. This immunosuppressive activity of IFN-gamma required
      functional type I IFN signaling. In IFN-alpha/beta receptor-deficient mice, IFN
      gamma treatment during effector phase of EAE exacerbated disease. Using an
      adoptive transfer EAE model, we found that T cell-intrinsic type I and II IFN
      signals are simultaneously required to establish chronic EAE by encephalitogenic
      Th1 cells. However, in Th17 cells loss of either IFN signals leads to the
      development of a severe chronic disease. The data imply that type I and II IFN
      signals have independent but nonredundant roles in restraining encephalitogenic
      Th17 cells in vivo. Collectively, our data show that type I and II IFNs function
      in an integrated manner to regulate pathogenesis in EAE. 

PMID- 23960240
TI  - The cellular source and target of IL-21 in K/BxN autoimmune arthritis.
AB  - IL-21 is a pluripotent cytokine that regulates B cell and plasma cell
      differentiation and is thought be an autocrine factor for follicular helper T
      cell (T(FH)) and Th17 differentiation. Although IL-21 has been implicated in
      autoimmune diseases, its relevant cellular source and target cells have not been
      well characterized. We investigated this issue in the K/BxN mouse model of
      autoimmune arthritis. Adoptive transfer of KRN-transgenic CD4+ T cells into
      appropriate hosts drives germinal center (GC) formation and autoantibody
      production against glucose-6-phosphate isomerase, leading to joint inflammation
      and destruction. By comparing transfer of T or B cells deficient in IL-21 or IL
      21R, we were able to dissect the contribution of each cell type. T cells
      deficient in IL-21 did not induce GC formation or autoantibody production, but
      they went through normal T(FH) differentiation. However, T cells lacking IL-21R
      induced Ab titers, GC B cell frequency, and arthritis development similar to wild
      type T cells, suggesting that IL-21 is not required for T(FH) differentiation and
      function. IL-21 acts on B cells, because IL-21R expression on B cells was
      required to induce disease. In contrast, Th17 cells, a T cell subset that also
      produces IL-21 and can provide help to B cells, are not required for the GC
      response and arthritis. These data have implications in developing effective
      therapies for rheumatoid arthritis and other Ab-mediated autoimmune diseases.

PMID- 23960241
TI  - MicroRNA-mediated epigenetic silencing of sirtuin1 contributes to impaired
      angiogenic responses.
AB  - RATIONALE: Transforming growth factor (TGF)-beta was linked to abnormal vessel
      function and can mediate impairment of endothelial angiogenic responses. Its
      effect on microRNAs and downstream targets in this context is not known.
      OBJECTIVE: To study the role of microRNAs in TGF-beta-mediated angiogenic
      activity. METHODS AND RESULTS: MicroRNA profiling after TGF-beta treatment of
      endothelial cells identified miR-30a-3p, along with other members of the miR-30
      family, to be strongly silenced. Supplementation of miR-30a-3p restored function
      in TGF-beta-treated endothelial cells. We identified the epigenetic factor methyl
      CpG-binding protein 2 (MeCP2) to be a direct and functional target of miR-30a-3p.
      Viral overexpression of MeCP2 mimicked the effects of TGF-beta, suggesting that
      derepression of MeCP2 after TGF-beta treatment may be responsible for impaired
      angiogenic responses. Silencing of MeCP2 rescued detrimental TGF-beta effects on
      endothelial cells. Microarray transcriptome analysis of MeCP2-overexpressing
      endothelial cells identified several deregulated genes important for endothelial
      cell function including sirtuin1 (Sirt1). In vivo experiments using endothelial
      cell-specific MeCP2 null or Sirt1 transgenic mice confirmed the involvement of
      MeCP2/Sirt1 in the regulation of angiogenic functions of endothelial cells.
      Additional experiments identified that MeCP2 inhibited endothelial angiogenic
      characteristics partly by epigenetic silencing of Sirt1. CONCLUSIONS: TGF-beta
      impairs endothelial angiogenic responses partly by downregulating miR-30a-3p and
      subsequent derepression of MeCP2-mediated epigenetic silencing of Sirt1.

PMID- 23960242
TI  - Development of anthropomorphic hand phantoms for personal dosimetry in 90Y
      Zevalin preparation and patient delivering.
AB  - Anthropomorphic tissue-equivalent hand phantoms were achieved to measure the
      extremity dose involved in Zevalin (90)Y-labelling and patient delivering
      procedure for radioimmunotherapy treatment of non-Hodgkin lymphoma. The extremity
      doses to hands and wrists of operators were measured by using thermoluminescent
      detectors mounted on the developed phantoms. Measurements of chest- and lens
      equivalent doses performed on a Rando phantom are also reported. 

PMID- 23960243
TI  - Comparison of electric field exposure measurement methods under power lines.
AB  - The object of the study was to investigate extremely low frequency (ELF) electric
      field exposure measurement methods under power lines. The authors compared two
      different methods under power lines: in Method A, the sensor was placed on a
      tripod; and Method B required the measurer to hold the meter horizontally so that
      the distance from him/her was at least 1.5 m. The study includes 20 measurements
      in three places under 400 kV power lines. The authors used two commercial three
      axis meters, EFA-3 and EFA-300. In statistical analyses, they did not find
      significant differences between Methods A and B. However, in the future, it is
      important to take into account that measurement methods can, in some cases,
      influence ELF electric field measurement results, and it is important to report
      the methods used so that it is possible to repeat the measurements. 

PMID- 23960244
TI  - Recovery Champions: A Personal View on Making Recovery Happen.

PMID- 23960246
TI  - Schizophrenia, Maslow's Hierarchy, and Compassion-Focused Therapy.

PMID- 23960247
TI  - The psychotherapeutic implications of functional neuroimaging studies of anxiety
      disorders.
AB  - OBJECTIVE: To explore and discuss the psychotherapeutic implications of
      functional neuroimaging findings in anxiety disorders. CONCLUSIONS: Therapeutic
      implications of the neural system dysfunctions found in functional neuroimaging
      studies of anxiety disorders include: emotional dysregulation can probably be
      found in all anxiety disorders except obsessive compulsive disorder and needs to
      be addressed; the probable salience of enhancing implicit emotion regulation in
      improving overall treatment outcome; the importance of addressing insecure
      attachment in establishing and maintaining the therapeutic relationship; the need
      to enhance the reward-approach system especially in chronic treatment-resistant
      patients; the need to address traumatic memory in anxiety disorders other than
      PTSD among those with a traumatic history. There is likely to be a need for
      therapeutic techniques and strategies of different psychotherapy schools to be
      utilized to adequately address the various neural dysfunctions in patients with
      anxiety disorders.

PMID- 23960245
TI  - Risk of mental illness in offspring of parents with schizophrenia, bipolar
      disorder, and major depressive disorder: a meta-analysis of family high-risk
      studies.
AB  - OBJECTIVE: Offspring of parents with severe mental illness (SMI; schizophrenia,
      bipolar disorder, major depressive disorder) are at an increased risk of
      developing mental illness. We aimed to quantify the risk of mental disorders in
      offspring and determine whether increased risk extends beyond the disorder
      present in the parent. METHOD: Meta-analyses of absolute and relative rates of
      mental disorders in offspring of parents with schizophrenia, bipolar disorder, or
      depression in family high-risk studies published by December 2012. RESULTS: We
      included 33 studies with 3863 offspring of parents with SMI and 3158 control
      offspring. Offspring of parents with SMI had a 32% probability of developing SMI
      (95% CI: 24%-42%) by adulthood (age >20). This risk was more than twice that of
      control offspring (risk ratio [RR] 2.52; 95% CI 2.08-3.06, P < .001). High-risk
      offspring had a significantly increased rate of the disorder present in the
      parent (RR = 3.59; 95% CI: 2.57-5.02, P < .001) and of other types of SMI (RR =
      1.92; 95% CI: 1.48-2.49, P < .001). The risk of mood disorders was significantly
      increased among offspring of parents with schizophrenia (RR = 1.62; 95% CI: 1.02
      2.58; P = .042). The risk of schizophrenia was significantly increased in
      offspring of parents with bipolar disorder (RR = 6.42; 95% CI: 2.20-18.78, P <
      .001) but not among offspring of parents with depression (RR = 1.71; 95% CI: 0.19
      15.16, P = .631). CONCLUSIONS: Offspring of parents with SMI are at increased
      risk for a range of psychiatric disorders and one third of them may develop a SMI
      by early adulthood.

PMID- 23960251
TI  - The synergistic effect of growing older with hoarding behaviors.
AB  - Clinically significant hoarding behaviors (HB) have been defined as acquisition
      of, and failure to discard, large numbers of items, which limits the use of one's
      home and causes functional impairment or distress. HB disproportionally affect
      adults aged 55 and older, and although research on HB has accelerated in the past
      decade, few studies focus on older adults. This qualitative study, based on
      grounded theory methodology, utilized interview data from 22 older adults with HB
      to understand the dynamic interaction between HB and the aging process.
      Participants described the specific ways that their chronic HB were complicated
      by changes in their health status, social context, and home setting, resulting in
      greater functional impairment and distress. By identifying these changes that
      commonly occur with age and their synergistic relationship with HB, nurses and
      other health professionals can develop targeted interventions to improve home
      safety and support the independence of these older adults. 

PMID- 23960252
TI  - Ethnicity, smoking status, and preterm birth as predictors of maternal locus of
      control.
AB  - A woman's psychological health can affect prenatal behaviors. The purpose of this
      study was to examine the relationship between maternal beliefs, prenatal
      behaviors, and preterm birth (PTB) in a multiethnic population. This was a
      planned secondary analysis of a cross-sectional trial of postpartum women with
      singleton gestation. In all, 210 participants were given the Fetal Health Locus
      of Control (FHLC) scale to measure three primary maternal beliefs that influenced
      their prenatal behaviors (Internal Control, Chance, Powerful Others). Women who
      experienced preterm delivery and those who smoked during pregnancy scored the
      Chance category significantly higher than those who delivered term infants (p =
      .05; p = .004, respectively). This suggests those who smoked during pregnancy had
      a greater degree of belief that Chance influenced their infant's health status.
      Cultural differences also emerged specific to the impact of health care providers
      on PTB; with Hispanic women scoring Powerful Others the highest among the groups
      (p = .02). Nurses can plan a critical role in identifying at-risk women (smoking,
      strong Chance beliefs) while providing a clear message that taking action and
      modifying high-risk behaviors can reduce risk for adverse pregnancy outcome. 

PMID- 23960253
TI  - Human expression QTLs are enriched in signals of environmental adaptation.
AB  - Expression quantitative trait loci (eQTLs) have been found to be enriched in
      trait-associated single-nucleotide polymorphisms (SNPs). However, whether eQTLs
      are adaptive to different environmental factors and its relative evolutionary
      significance compared with nonsynonymous SNPs (NS SNPs) are still elusive.
      Compiling environmental correlation data from three studies for more than 500,000
      SNPs and 42 environmental factors, including climate, subsistence, pathogens, and
      dietary patterns, we performed a systematic examination of the adaptive patterns
      of eQTLs to local environment. Compared with intergenic SNPs, eQTLs are
      significantly enriched in the lower tail of a transformed rank statistic in the
      environmental correlation analysis, indicating possible adaptation of eQTLs to
      the majority of 42 environmental factors. The mean enrichment of eQTLs across 42
      environmental factors is as great as, if not greater than, that of NS SNPs. The
      enrichment of eQTLs, although significant across all levels of recombination
      rate, is inversely correlated with recombination rate, suggesting the presence of
      selective sweep or background selection. Further pathway enrichment analysis
      identified a number of pathways with possible environmental adaption from eQTLs.
      These pathways are mostly related with immune function and metabolism. Our
      results indicate that eQTLs might have played an important role in recent and
      ongoing human adaptation and are of special importance for some environmental
      factors and biological pathways. 

PMID- 23960255
TI  - Fruit and vegetable consumption with risk of abdominal aortic aneurysm.
AB  - BACKGROUND: Dietary factors affecting the risk of developing abdominal aortic
      aneurysm (AAA) are scarcely investigated. The aim of this study was to
      investigate the associations of fruit and vegetable consumption with the risk to
      develop AAA. METHODS AND RESULTS: The prospective Cohort of Swedish Men and the
      Swedish Mammography Cohort, consisting of 44,317 men and 36,109 women, 46 to 84
      years of age at the start of the 13-year follow-up (1998-2010), were used. Fruit
      and vegetable consumption was assessed at baseline with a 96-item food-frequency
      questionnaire. By linkage to the Swedish Inpatient Register and the Swedish
      Vascular Registry (Swedvasc), 1086 primary cases of AAA (222 ruptured) were
      identified. Cox proportional hazards models were used to estimate hazard ratios
      with 95% confidence intervals (CIs). Those in the highest quartile of fruit
      consumption (>2.0 servings/d), in comparison with those in the lowest quartile
      (<0.7 servings/d), had a 25% (95% CI, 9%-38%) lower risk of AAA, and a 43% (95%
      CI, 11%-64%) lower risk of ruptured AAA, specifically. Consumption of 2 fruits
      per day was associated with 31% (95% CI, 11%-47%) lower risk of nonruptured AAA,
      and 39% (95% CI, 1%-63%) lower risk of ruptured AAA, in comparison with no
      consumption of fruit. No association was observed between vegetable consumption
      and AAA risk. CONCLUSIONS: We observed an inverse association between consumption
      of fruit, but not vegetables, and the risk of AAA, with a more pronounced
      association with ruptured AAA.

PMID- 23960256
TI  - Repair of the regurgitant bicuspid or tricuspid aortic valve: background,
      principles, and outcomes.

PMID- 23960254
TI  - Phylogenomics and analysis of shared genes suggest a single transition to
      mutualism in Wolbachia of nematodes.
AB  - Wolbachia, endosymbiotic bacteria of the order Rickettsiales, are widespread in
      arthropods but also present in nematodes. In arthropods, A and B supergroup
      Wolbachia are generally associated with distortion of host reproduction. In
      filarial nematodes, including some human parasites, multiple lines of
      experimental evidence indicate that C and D supergroup Wolbachia are essential
      for the survival of the host, and here the symbiotic relationship is considered
      mutualistic. The origin of this mutualistic endosymbiosis is of interest for both
      basic and applied reasons: How does a parasite become a mutualist? Could
      intervention in the mutualism aid in treatment of human disease? Correct rooting
      and high-quality resolution of Wolbachia relationships are required to resolve
      this question. However, because of the large genetic distance between Wolbachia
      and the nearest outgroups, and the limited number of genomes so far available for
      large-scale analyses, current phylogenies do not provide robust answers. We
      therefore sequenced the genome of the D supergroup Wolbachia endosymbiont of
      Litomosoides sigmodontis, revisited the selection of loci for phylogenomic
      analyses, and performed a phylogenomic analysis including available complete
      genomes (from isolates in supergroups A, B, C, and D). Using 90 orthologous genes
      with reliable phylogenetic signals, we obtained a robust phylogenetic
      reconstruction, including a highly supported root to the Wolbachia phylogeny
      between a (A + B) clade and a (C + D) clade. Although we currently lack data from
      several Wolbachia supergroups, notably F, our analysis supports a model wherein
      the putatively mutualist endosymbiotic relationship between Wolbachia and
      nematodes originated from a single transition event. 

PMID- 23960257
TI  - Overview of the 2013 Food and Drug Administration Circulatory System Devices
      Panel meeting on the MitraClip Delivery System.

PMID- 23960258
TI  - ECG Response: August 20, 2013.

PMID- 23960259
TI  - Hypertrophic cardiomyopathy with mitral inflow obstruction and severe pulmonary
      hypertension.

PMID- 23960260
TI  - Survived sudden cardiac death in a young marathon runner: cardiac ischemic event
      attributed to an interarterial course of the right coronary artery.

PMID- 23960262
TI  - Letter by Prutkin regarding article, "Janeway lesions: an old sign revisited".

PMID- 23960263
TI  - Response to letter regarding article, "Janeway lesions: an old sign revisited".

PMID- 23960265
TI  - Pediatric hypertension: the year in review.

PMID- 23960266
TI  - CHOA concussion consensus: establishing a uniform policy for academic
      accommodations.
AB  - Concussion research generally centers on physical challenges, though aspects such
      as social functioning and returning to school also warrant attention in pediatric
      populations. Restoring academic performance postconcussion remains a challenge.
      Here we provide recommendations addressing a uniform policy for pediatric
      concussion patients in academic institutions. Tools that may minimize difficulty
      with academic re-entry include independent educational evaluations,
      individualized educational programs (IEPs), student support teams (SSTs), letters
      of academic accommodation, time off, and 504 Plans. Recognition and treatment is
      crucial for symptom relief and prevention of functional disruption, as is
      specialist referral during the acute window. We recommend early intervention with
      a letter of academic accommodation and SST and suggest that 504 Plans and IEPs be
      reserved for protracted or medically complicated cases. Students with concussion
      should be observed for anxiety and depression because these symptoms can lead to
      prolonged recovery, decreased quality of life, and other social challenges. 

PMID- 23960267
TI  - Meeting the challenge: responding to health care needs of homeless youth.
AB  - PURPOSE: This article presents a worldview of youth who are victims of
      homelessness. A view of family dynamics and how they affect the emotional,
      psychological, social, and physical health of homeless youth is presented.
      RESULTS: Homeless youth and their families are at high risk for poor health
      outcomes. Those who present for health care services are least likely to return
      to the same site for follow-up care. CONCLUSION: Understanding the dynamics of
      homelessness and its effect on youth and family will facilitate efforts to engage
      the family and increase the likelihood for follow-up with the same provider. A
      patient-centered cognitive approach when managing these youth and their family
      will improve communication, potentiate engagement, whet creative decision making,
      and facilitate continuity of care.

PMID- 23960268
TI  - The generalist-specialist interface: not a zero-sum game.

PMID- 23960269
TI  - Reorganizing the General Clinical Research Center to improve the clinical and
      translational research enterprise.
AB  - In 2010, Virginia Commonwealth University (VCU) was granted a Clinical and
      Translational Science Award which prompted reorganization and expansion of their
      clinical research infrastructure. A case study approach is used to describe the
      implementation of a business and cost recovery model for clinical and
      translational research and the transformation of VCU's General Clinical Research
      Center and Clinical Trials Office to a combined Clinical Research Services
      entity. We outline the use of a Plan, Do, Study, Act cycle that facilitated a
      thoughtful transition process, which included the identification of required
      changes and cost recovery processes for implementation. Through this process, the
      VCU Center for Clinical and Translational Research improved efficiency, increased
      revenue recovered, reduced costs, and brought a high level of fiscal
      responsibility through financial reporting. 

PMID- 23960270
TI  - Common metrics to assess the efficiency of clinical research.
AB  - The Clinical and Translational Science Award (CTSA) program was designed by the
      National Institutes of Health (NIH) to develop processes and infrastructure for
      clinical and translational research throughout the United States. The CTSA
      initiative now funds 61 institutions. In 2012, the National Center for Advancing
      Translational Sciences, which administers the CTSA Program, charged the
      Evaluation Key Function Committee of the CTSA Consortium to develop common
      metrics to assess the efficiency of clinical research processes and outcomes. At
      this writing, the committee has identified 15 metrics in six categories. It has
      also developed a standardized protocol to define, pilot test, refine, and
      implement the metrics. The ultimate goal is to learn critical lessons about how
      to evaluate the processes and outcomes of clinical research within the CTSAs and
      beyond. This article describes the work involved in developing and applying
      common metrics and benchmarks of evaluation. 

PMID- 23960271
TI  - Factor structure of the Clinical Research Appraisal Inventory (CRAI).
AB  - The Clinical Research Appraisal Inventory (CRAI) is a 92-item measure covering 10
      domains of research self-efficacy. A known behavioral antecedent, reliable and
      valid measures of self-efficacy represent a potentially useful tool in the
      evaluation of research training program efficacy. However, few formal
      psychometric studies of this instrument exist. Using exploratory factor analysis,
      we examine the CRAI's dimensional structure in a new sample of clinical research
      trainees. In contrast to the multidimensional solutions reported previously, CRAI
      responses in the present sample were unambiguously one-dimensional (as suggested
      by a dominant single Eigenvalue and parallel analysis). This discrepant finding
      may reflect sample differences in research experience, as unlike previous
      studies, participants had all already obtained a professional degree. The CRAI's
      dimensional structure may coalesce into a smaller number of factors as research
      experience is acquired, and investigators should be mindful of this possibility
      in future studies of the instrument.

PMID- 23960272
TI  - BRAF mutation is associated with the unique morphology of traditional serrated
      adenoma of the colorectum.
AB  - Traditional serrated adenoma (TSA) consists of glands with tall cells and short
      cells. Two kinds of cells alternate to give a unique serrated configuration. The
      aim of this study was to identify the relationship between the alterations of
      both Wnt and serrated pathways and the unique morphology of TSAs. The tall and
      short cells in 28 TSAs were separated by microdissection. Semi-nested polymerase
      chain reaction was performed to detect the mutations of BRAF, beta-catenin, APC,
      and KRAS. BRAF mutations were observed in 22 of 28 (78.6%) TSAs, and all
      mutations occurred at the tall cells. In conclusion, BRAF mutation is associated
      with the serrated morphology of TSAs. Genetic alterations in both the serrated
      pathway and the Wnt signaling pathway may both contribute to TSAs. 

PMID- 23960273
TI  - Corneal Langerhans cell and dry eye examinations in ankylosing spondylitis.
AB  - APCs of the ocular surface, including corneal Langerhans cells (LCs), offer the
      opportunity to gain insight into the activity of innate immunity. We examined
      corneal LCs and dry eye parameters in ankylosing spondylitis (AS). Twenty-four AS
      patients with varying degrees of disease activity and 24 healthy participants
      were enrolled. Central and peripheral LC numbers, and Langerhans cell morphology
      (LCM) were assessed with in vivo laser confocal microscopy. In addition, ocular
      surface disease index, lid parallel conjunctival folds, tear break up time, and
      Schirmer test were evaluated. LC densities and central LCM were greater in AS
      patients than in the controls. Moreover, LCM was significantly greater in
      patients with higher systemic inflammation according to elevated C-reactive
      protein (CRP). Also, tear production was greatly suppressed in patients with more
      severe onset of the systemic inflammation according to the Bath Ankylosing
      Spondylitis Disease Activity Index and elevated CRP. Greater corneal LC density
      and LCM in AS may reflect an increased activation state of the innate immune
      system of the cornea in AS, which correlates with the systemic activity of AS
      even without ocular symptoms. Nonetheless, higher systemic inflammation might
      impair tear production, and it might partly explain the dry eye mechanism. 

PMID- 23960274
TI  - Surgical management of Mason type III radial head fractures.
AB  - The evidence for optimal management of Mason type III fracture of radial head is
      unclear hence a systematic review of the published literature was performed in
      April 2012. This review includes 5 prospective studies (including 2 randomized
      trials), 4 retrospective studies and 9 case series. No study can be interpreted
      as level 1 evidence. Level 2 and 3 evidence provides some insight into the
      success of each modality through subjective and objective measurements of
      function and complication rates. Radial head replacement, open reduction internal
      fixation (ORIF) and radial head resection all provide satisfactory outcomes for
      patients in most cases. One treatment modality cannot be recommended over any
      other due to the small number of clinical trials and cases included in each
      study. Further randomized control trials are needed to evaluate the full benefits
      and shortcomings of each of the different surgical treatment modalities. 

PMID- 23960275
TI  - Reduction techniques in the management of atlantoaxial subluxation.
AB  - BACKGROUND: The traditional approach to atlantoaxial subluxation which is
      irreducible after traction is transoral decompression and reduction or odontoid
      excision and posterior fixation. Transoral approach is associated with
      comorbidities. However using a posterior approach a combination of atlantoaxial
      joint space release and a variety of manipulation procedures, optimal or near
      optimal reduction can be achieved. We analysed our results in this study based on
      above procedure. MATERIALS AND METHODS: 66 cases treated over a 5 year period
      were evaluated retrospectively. Three cases treated by occipito cervical fusion
      were not included in the study. The remaining 63 cases were classified into three
      types. All except two cases were subjected to primary posterior C1-C2 joint space
      dissection and release followed by on table manipulation which was tailored to
      treat the type of atlantoaxial subluxation. Optimal or near optimal reduction was
      possible in all cases. An anterior transoral decompression was needed only in two
      cases where a bony growth (callus) between the C1 anterior arch and the odontoid
      precluded reduction by posterior manipulation. All cases then underwent posterior
      fusion and fixation procedures. Patients were neurologically and radiologically
      evaluated at regular followups to assess fusion and stability for a minimum
      period of 6 months. RESULTS: Of the 63 cases who underwent posterior
      manipulation, 49 cases achieved optimum reduction and the remaining 14 cases
      showed near optimal reduction. Two cases expired in the postoperative period.
      None of the remaining cases showed neurological worsening after the procedure.
      Evaluation at 6 months after surgery revealed good stability and fusion in all
      except three cases. CONCLUSION: Atlantoaxial joint release and manipulation can
      be used to achieve reduction in most cases of atlantoaxial subluxation, obivating
      the need of transoral odontoid excision.

PMID- 23960276
TI  - Complications in lumbar spine surgery: A retrospective analysis.
AB  - BACKGROUND: Surgical treatment of adult lumbar spinal disorders is associated
      with a substantial risk of intraoperative and perioperative complications. There
      is no clearly defined medical literature on complication in lumbar spine surgery.
      Purpose of the study is to retrospectively evaluate intraoperative and
      perioperative complications who underwent various lumbar surgical procedures and
      to study the possible predisposing role of advanced age in increasing this rate.
      MATERIALS AND METHODS: From 2007 to 2011 the number and type of complications
      were recorded and both univariate, (considering the patients' age) and a
      multivariate statistical analysis was conducted in order to establish a possible
      predisposing role. 133 were lumbar disc hernia treated with microdiscetomy, 88
      were lumbar stenosis, treated in 36 cases with only decompression, 52 with
      decompression and instrumentation with a maximum of 2 levels. 26 patients showed
      a lumbar fracture treated with percutaneous or open screw fixation. 12 showed a
      scoliotic or kyphotic deformity treated with decompression, fusion and
      osteotomies with a maximum of 7.3 levels of fusion (range 5-14). 70 were
      spondylolisthesis treated with 1 or more level of fusion. In 34 cases a fusion
      till S1 was performed. RESULTS: Of the 338 patients who underwent surgery, 55
      showed one or more complications. Type of surgical treatment (P = 0.004), open
      surgical approach (open P = 0.001) and operative time (P = 0.001) increased the
      relative risk (RR) of complication occurrence of 2.3, 3.8 and 5.1 respectively.
      Major complications are more often seen in complex surgical treatment for severe
      deformities, in revision surgery and in anterior approaches with an occurrence of
      58.3%. Age greater than 65 years, despite an increased RR of perioperative
      complications (1.5), does not represent a predisposing risk factor to
      complications (P = 0.006). CONCLUSION: Surgical decision-making and exclusion of
      patients is not justified only by due to age. A systematic preoperative
      evaluation should always be performed in order to stratify risks and to guide
      decision-making for obtaining the best possible clinical results at lower risk,
      even for elderly patients.

PMID- 23960277
TI  - Risk factors for adjacent segment degeneration after surgical correction of
      degenerative lumbar scoliosis.
AB  - BACKGROUND: Degenerative lumbar scoliosis surgery can lead to development of
      adjacent segment degeneration (ASD) after lumbar or thoracolumbar fusion. Its
      incidence, risk factors, morbidity and correlation between radiological and
      clinical symptoms of ASD have no consensus. We evaluated the correlation between
      the occurrence of radiologic adjacent segment disease and certain imperative
      parameters. MATERIALS AND METHODS: 98 patients who had undergone surgical
      correction and lumbar/thoracolumbar fusion with pedicle screw instrumentation for
      degenerative lumbar scoliosis with a minimum 5 year followup were included in the
      study. We evaluated the correlation between the occurrence of radiologic adjacent
      segment disease and imperative patient parameters like age at operation, sex,
      body mass index (BMI), medical comorbidities and bone mineral density (BMD). The
      radiological parameters taken into consideration were Cobb's angle, angle type,
      lumbar lordosis, pelvic incidence, intercristal line, preoperative existence of
      an ASD on plain radiograph and magnetic resonance imaging (MRI) and surgical
      parameters were number of the fusion level, decompression level, floating OP
      (interlumbar fusion excluding L5-S1 level) and posterolateral lumbar interbody
      fusion (PLIF). Clinical outcomes were assessed with the Visual Analogue Score
      (VAS) and Oswestry Disability Index (ODI). RESULTS: ASD was present in 44 (44.9%)
      patients at an average period of 48.0 months (range 6-98 months). Factors related
      to occurrence of ASD were preoperative existence of disc degeneration (as
      revealed by MRI) and age at operation (P = 0.0001, 0.0364). There were no
      statistically significant differences between radiological adjacent segment
      degeneration and clinical results (VAS, P = 0.446; ODI, P = 0.531). CONCLUSIONS:
      Patients over the age of 65 years and with preoperative disc degeneration (as
      revealed by plain radiograph and MRI) were at a higher risk of developing ASD.

PMID- 23960278
TI  - Solid and hollow pedicle screws affect the electrical resistance: A potential
      source of error with stimulus-evoked electromyography.
AB  - BACKGROUND: Although stimulus evoked electromyography (EMG) is commonly used to
      confirm the accuracy of pedicle screw placement. There are no studies to
      differentiate between solid screws and hollow screws to the electrical resistance
      of pedicle screws. We speculate that the electrical resistance of the solid and
      hollow pedicle screws may be different and then a potential source of error with
      stimulus-evoked EMG may happen. MATERIALS AND METHODS: Resistance measurements
      were obtained from 12 pedicle screw varieties (6 screws of each manufacturer)
      across the screw shank based on known constant current and measured voltage. The
      voltage was measured 5 times at each site. RESULTS: Resistance of all solid
      screws ranged from 0.084 Omega to 0.151 Omega (mean =0.118 +/- 0.024 Omega) and
      hollow screws ranged from 0.148 Omega to 0.402 Omega (mean = 0.285 +/- 0.081
      Omega). There was a significant difference of resistance between the solid screws
      and hollow screws (P < 0.05). The screw with the largest diameter no matter solid
      screws or hollow screws had lower resistance than screws with other diameters. No
      matter in solid screws group or hollow screws group, there were significant
      differences (P < 0.05) between the 5.0 mm screws and 6.0 mm screws, 6.0 mm screws
      and 7.0 mm screws, 5.0 mm screws and 7.0 mm screws, 4.5 mm screws and 5.5 mm
      screws, 5.5 mm screws and 6.5 mm screws, 4.5 mm screws and 6.5 mm screws. The
      resistance of hollow screws was much larger than the solid screws in the same
      diameter group (P < 0.05). CONCLUSIONS: Hollow pedicle screws have the potential
      for high electrical resistance compared to the solid pedicle screws and therefore
      may affect the EMG response during stimulus-evoked EMG testing in pedicle screw
      fixation especially in minimally invasive percutaneous pedical screw fixation
      surgery.

PMID- 23960279
TI  - Results of Wagner SL revision stem with impaction bone grafting in revision total
      hip arthroplasty.
AB  - BACKGROUND: As the number of total hip arthroplasties (THAs) performed increases,
      so do the number of required revisions. Impaction bone grafting with Wagner SL
      Revision stem is a good option for managing bone deficiencies arising from
      aseptic osteolysis. We studied the results of cementless diaphyseal fixation in
      femoral revision after total hip arthroplasty and whether there was spontaneous
      regeneration of bone stock in the proximal femur after the use of Wagner SL
      Revision stem (Zimmer, Warsaw, IN, USA) with impaction bone grafting. MATERIALS
      AND METHODS: We performed 53 hip revisions using impaction bone grafting and
      Wagner SL Revision stems in 48 patients; (5 cases were bilateral) for variety of
      indications ranging from aseptic osteolysis to preiprosthetic fractures. The
      average age was 59 years (range 44-68 years). There were 42 male and 6 female
      patients. Four patients died after surgery for reasons unrelated to surgery. 44
      patients were available for complete analysis. RESULTS: The mean Harris Hip Score
      was 42 before surgery and improved to 86 by the final followup evaluation at a
      mean point of 5.5 years. Of the 44 patients, 87% (n=39) had excellent results and
      10% (n=5) had good results. The stem survival rate was 98% (n=43). CONCLUSION:
      Short term results for revision THA with impaction bone grafting and Wagner SL
      revision stems are encouraging. However, it is necessary to obtain long term
      results through periodic followup evaluation, as rate of complications may
      increase in future.

PMID- 23960280
TI  - Lateral malleolus hook plate for comminuted Weber A and B fractures: A
      retrospective study.
AB  - BACKGROUND: The goal of managing the comminuted fracture of lateral malleolus is
      to restore length, rotation and alignment which might be more challenging with
      extensive comminution around the area of the distal tip. The common
      osteosynthesis techniques such as the one-third tubular plate, tension band
      wiring, K-wires, screws, or intramedullary nail may be insufficient in cases with
      a comminuted lateral malleolus. The anatomical hook plate is an alternative
      implant in such cases. We present our results of the comminuted lateral malleolar
      fractures (Weber A, B), managed by open reduction and internal fixation (ORIF)
      with an anatomical hook plate of lateral malleolus (Konigsee Implant Company,
      Germany). MATERIALS AND METHODS: We retrospectively reviewed 20 patients of
      comminuted fracture of distal lateral malleolus between 2008 and 2010. There were
      12 males and 8 females, right side was involved in 18 patients and left in 2. The
      mean age was 51.9 years (range 18-75 years). The fractures were categorized by
      Denis-Weber classification type A (n=1), B1 (n=1), B2 (n=13) and B3 (n=5).
      Nineteen cases were of closed injury and one of open injury (Gustilo Anderson
      type II). These patients underwent ORIF with a lateral malleolus anatomical hook
      plate. Followup including radiographs and clinical examinations were performed.
      The American Orthopedic Foot and Ankle Society (AOFAS) ankle hindfoot scores were
      documented at followups. RESULTS: The mean followup was 21.4 months (range 16-27
      months). The average AOFAS score was 94.3 (range 78-100) points. A stable
      anatomic reduction and bony union were obtained in all the cases. The average
      time was 3.1 months (range 2.5-4 months). Four cases had complications like
      posttraumatic osteoarthritis, hardware impingement and superficial wound
      infection. CONCLUSION: A reasonably good stability can be obtained in distal most
      comminuted fractures of lateral malleolus with a lateral malleolus anatomical
      hook plate. We believe this method to be a reasonable treatment option for a
      distal lateral comminuted malleolar fracture when other common fixations are
      insufficient to fix the fragments.

PMID- 23960281
TI  - Classification of relapse pattern in clubfoot treated with Ponseti technique.
AB  - BACKGROUND: Relapse of clubfoot deformity following correction by Ponseti
      technique is not uncommon. The relapsed feet progress from flexible to rigid if
      left untreated and can become as severe as the initial deformity. No definitive
      classification exists to assess a relapsed clubfoot. Some authors have used the
      Pirani score to rate the relapse while others have used descriptive terms. The
      purpose of this study is to analyze the relapse pattern in clubfeet that have
      undergone treatment with the Ponseti method and propose a simple classification
      for relapsed clubfeet. MATERIALS AND METHODS: Ninety-one children (164 feet) with
      idiopathic clubfeet who underwent treatment with Ponseti technique presented with
      relapse of the deformity. There were 68 boys and 23 girls. Mean age at
      presentation for casting was 10.71 days (range 7-22 days). Seventy three children
      (146 feet, 80%) had bilateral involvement and 18 (20%) had unilateral clubfeet.
      The mean Pirani Score was 5.6 and 5.5 in bilateral and unilateral groups
      respectively. Percutaneous heel cord tenotomy was done in 65 children (130 feet,
      89%) in the bilateral group and in 12 children (66%) with unilateral clubfoot.
      RESULTS: Five relapse patterns were identified at a mean followup of 4.5 years
      (range 3-5 years) which forms the basis of this study. These relapse patterns
      were classified as: Grade IA: decrease in ankle dorsiflexion from15 degrees to
      neutral, Grade IB: dynamic forefoot adduction or supination, Grade IIA - rigid
      equinus, Grade IIB - rigid adduction of forefoot/midfoot complex and Grade III:
      combination of two or more deformities: Fixed equinus, varus and forefoot
      adduction. In the bilateral group, 21 children (38 feet, 28%) had Grade IA
      relapse. Twenty four children (46 feet, 34%) had dynamic intoeing (Grade IB) on
      walking. Thirteen children (22 feet, 16%) had true ankle equinus of varying
      degress (Grade IIA); eight children (13 feet, 9.7%) had fixed adduction deformity
      of the forefoot (Grade IIB) and seven children (14 feet, 10.7%) had two or more
      fixed deformities. In the unilateral group seven cases (38%) had reduced
      dorsiflexion (Grade IA), six (33%) had dynamic adduction (Grade IB), two (11%)
      had fixed equinus and adduction respectively (Grade IIA and IIB) and one (5%)
      child had fixed equinus and adduction deformity (Grade III). The relapses were
      treated by full time splint application, re-casting, tibialis anterior transfer,
      posterior release, corrective lateral closing wedge osteotomy and a comprehensive
      subtalar release. Splint compliance was compromised in both groups. CONCLUSION:
      Relapse pattern in clubfeet can be broadly classified into three distinct
      subsets. Early identification of relapses and early intervention will prevent
      major soft tissue surgery. A universal language of relapse pattern will allow
      comparison of results of intervention.

PMID- 23960282
TI  - Results of a bone splint technique for the treatment of lower limb deformities in
      children with type I osteogenesis imperfecta.
AB  - BACKGROUND: Children with osteogenesis imperfecta (OI) can suffer from frequent
      fractures and limb deformities, resulting in impaired ambulation. Osteopenia and
      thin cortices complicate orthopedic treatment in this group. This study evaluates
      the clinical results of a bone splint technique for the treatment of lower limb
      deformities in children with type I OI. The technique consists of internal
      plating combined with cortical strut allograft fixation. MATERIALS AND METHODS:
      We prospectively followed nine children (five boys, four girls) with lower limb
      deformities due to type I OI, who had been treated with the bone splint technique
      (11 femurs, four tibias) between 2003 and 2006. The fracture healing time,
      deformity improvement, ambulation ability and complications were recorded to
      evaluate treatment effects. RESULTS: At the time of surgery the average age in
      our study was 7.7 years (range 5-12 years). The average length of followup was 69
      months (range 60-84 months). All patients had good fracture healing with an
      average healing time of 14 weeks (range 12-16 weeks) and none experienced further
      fractures, deformity, or nonunion. The fixation remained stable throughout the
      procedure in all cases, with no evidence of loosening or breakage of screws and
      the deformity and mobility significantly improved after surgery. Of the two
      children confined to bed before surgery, one was able to walk on crutches and the
      other needed a wheelchair. The other seven patients could walk without walking
      aids or support like crutches. CONCLUSIONS: These findings suggest that the bone
      splint technique provides good mechanical support and increases the bone mass. It
      is an effective treatment for children with OI and lower limb deformities.

PMID- 23960283
TI  - Sideswipe injuries around the elbow: Management and functional evaluation.
AB  - INTRODUCTION: Sideswipe injuries constitute a subgroup of complex elbow trauma.
      Almost all of these are high energy open injuries. There is no fixed protocol
      that is followed in the earlier studies. The injury pattern is grotesque and ill
      managed with poor functional outcome. We report the functional outcome in our
      series of patients who sustained sideswipe injuries. MATERIALS AND METHODS:
      Thirty four patients presenting with sideswipe injuries around the elbow were
      managed and functional results evaluated. The patients were followed for 15-94
      months (mean 74 months). 32 of these were males and two were females. The
      injuries were sustained between 8 years and 48 years age group (mean 30 years).
      The right side was affected in 20 and left side was injured in 14 patients. Road
      traffic accident was the cause in all patients. Principles of management followed
      were (1) debridement and stabilization of fractures, (2) vascular repair, (3)
      redebridement, (4) nerve repair and (5) soft tissue cover. An external fixator
      was used for fracture stabilization in 20 patients with open fractures. Internal
      fixation was used as a stabilization modality in 12 patients. Primary nerve
      repair was carried out in 4 cases. In case of segmental loss, tendon transfers or
      nerve grafting was carried out at a later date once softtissue healing was
      complete. Soft tissue coverage was provided within 24-48 h of injury. Results
      were evaluated using the Mayo elbow performance score. RESULTS: The average Mayo
      elbow performance score was 70. Excellent results (score > 90) in accordance with
      Mayo elbow score were seen in 30% of the patients. Good results (score 75-89)
      were seen in 33% of the patients. CONCLUSION: Sideswipe injuries should be
      managed timely, aggressively and an algorithmic protocol should be followed to
      achieve best results. The injury pattern is distinct for which a multispecialty
      approach is needed and an orthopedic, vascular and plastic surgeon must be
      involved. Limb salvage is possible in most cases.

PMID- 23960284
TI  - Bony defect repair in rabbit using hybrid rapid prototyping polylactic-co
      glycolic acid/beta-tricalciumphosphate collagen I/apatite scaffold and bone
      marrow mesenchymal stem cells.
AB  - BACKGROUND: In bone tissue engineering, extracellular matrix exerts critical
      influence on cellular interaction with porous biomaterial and the apatite playing
      an important role in the bonding process of biomaterial to bone tissue. The aim
      of this study was to observe the therapeutic effects of hybrid rapid prototyping
      (RP) scaffolds comprising polylactic-co-glycolic acid (PLGA), beta
      tricalciumphosphate (beta-TCP), collagen I and apatite (PLGA/beta-TCP-collagen
      I/apatite) on segmental bone defects in conjunction with combination with bone
      marrow mesenchymal stem cells (BMSCs). MATERIALS AND METHODS: BMSCs were seeded
      into the hybrid RP scaffolds to repair 15 mm defect in the radius of rabbits.
      Radiograph, microcomputed tomography and histology were used to evaluate new bone
      formation. RESULTS: Radiographic analysis done from 12 to 36 weeks postoperative
      period demonstrated that new bone formed at the radial defect site and continues
      to increase until the medullary cavity is recanalized and remodelling is
      complete. The bone defect remained unconnected in the original RP scaffolds
      (PLGA/beta-TCP) during the whole study. Histological observations conformed to
      the radiographic images. In hybrid RP scaffold group, woven bone united the
      radial defect at 12 weeks and consecutively remodeled into lamellar bone 24 weeks
      postoperation and finally matured into cortical bone with normal marrow cavity
      after another 12 weeks. No bone formation but connective tissue has been detected
      in RP scaffold at the same time. CONCLUSION: Collagen I/apatite sponge composite
      coating could improve new bone formation in vivo. The hybrid RP scaffold of
      PLGA/beta-TCP skeleton with collagen I/apatite sponge composite coating is a
      promising candidate for bone tissue engineering.

PMID- 23960285
TI  - Effects of a selective cyclooxygenase-2 inhibitor (celecoxib) on fracture healing
      in rats.
AB  - BACKGROUND: Several studies suggested that celecoxib interferes with bone healing
      while others contradict these findings. This study was conducted to investigate
      the effects of celecoxib on bone healing in rats femur mold with a dose based on
      body surface area conversion. MATERIALS AND METHODS: 72 adult female Sprague
      Dawley rats were randomly divided into three groups after the internal fixation
      operation of nondisplaced transverse mid diaphyseal fractures of the right
      femurs. Each group was treated with 1% methylcellulose, celecoxib (21 mg/kg/d)
      for 1 week, or celecoxib (21 mg/kg/d) for 4 weeks after surgeries respectively.
      Bone healing scores and callus formation were evaluated by radiographs at 3, 4, 6
      weeks after surgeries. Half of these rats were sacrificed for histological
      analysis at 4 weeks after surgery. The remaining fractured femurs were evaluated
      by biomechanical tests at 6 weeks after surgery. RESULTS: The mean radiographic
      scores for fracture healing of both short and long term groups were lower than
      that of the control group and the differences among the three groups were
      statistically significant (P < 0.05) at 3, 4, 6 weeks after surgery. The mean
      bone trabecula density of both groups was smaller than that of the control group
      and the differences were also statistically significant (P < 0.05) at 4 week. The
      maximum load, total energy and stiffness in both the short term and long term
      groups were significantly decreased compared with those in the control group (P <
      0.05) at 6 week. CONCLUSION: Both short term and long term sustained use of
      celecoxib in rat models has significantly inhibitory effects on rat fracture
      healing.

PMID- 23960286
TI  - Correlation of vitamin D, bone mineral density and parathyroid hormone levels in
      adults with low bone density.
AB  - BACKGROUND: Bone mineral densiy (BMD) is known to be affected by serum 25
      hydroxyvitamin D (25(OH) D) levels, intact parathyroid hormone (iPTH) levels.
      Indian data pertinent to above observation is scant. Our study aimed to
      investigate the relationships between serum 25-hydroxyvitamin D (25(OH) D)
      levels, intact parathyroid hormone (iPTH) levels and bone mineral density (BMD)
      in a cohort of Indian patients. MATERIALS AND METHODS: Adults with or without
      fragility fractures with low BMD at the hip or lumbar spine were evaluated
      clinically along with laboratory investigations. T-scores of the hip and spine
      were derived from BMD-DEXA (dual-energy X-ray absorptiometry). Multivariate
      regression models were used to investigate the relationships between serum 25(OH)
      D, iPTH and BMD. RESULTS: Total of 102 patients (male:female = 38:64) with a mean
      age of 62.5 +/- 6.4 years were included in the study. Forty-four patients had
      osteopenia. Osteoporosis was present in 58 patients. The mean values for serum
      25(OH) D and iPTH levels were 21.3 +/- 0.5 ng/ml and 53.1 +/- 22.3 pg/ml,
      respectively. In 84.3% of patients, serum 25(OH) D levels were below 30 ng/ml
      (Normal = 30-74 ng/ml), confirming vitamin D deficiency. There was no association
      between 25(OH) D levels and BMD at the hip or lumbar spine (P = 0.473 and 0.353,
      respectively). Both at the hip and lumbar spine; iPTH levels, male gender, body
      mass index (BMI) and age were found to be significant predictors of BMD. Patients
      with higher BMI had significantly lower BMD and T-score. At levels <30 ng/ml,
      25(OH) D was negatively associated with iPTH (P = 0.041). CONCLUSION: Among our
      cohort of patients with low BMD, no direct relationship between serum 25(OH) D
      levels and BMD was observed. However, a negative correlation between iPTH and
      25(OH) D at serum 25(OH) D concentrations <30 ng/ml. Serum iPTH levels showed a
      significant negative association with BMD at the hip and lumbar spine. Our
      findings underscore the critical role of parathyroid hormone in bone metabolism
      and health.

PMID- 23960287
TI  - Ogilvie's syndrome following posterior spinal arthrodesis for scoliosis.
AB  - We report Ogilvie's syndrome following posterior spinal arthrodesis on a patient
      with thoracic and lumbar scoliosis associated with intraspinal anomalies.
      Postoperative paralytic ileus can commonly complicate scoliosis surgery.
      Ogilvie's syndrome as a cause of abdominal distension and pain has not been
      reported following spinal deformity correction and can mimic post-surgical ileus.
      12 year old female patient with double thoracic and lumbar scoliosis associated
      with Arnold-Chiari 1 malformation and syringomyelia. The patient underwent
      posterior spinal fusion from T4 to L3 with segmental pedicle screw
      instrumentation and autogenous iliac crest grafting. She developed abdominal
      distension and pain postoperatively and this deteriorated despite conservative
      management. Repeat ultrasounds and abdominal computer tomography scans ruled out
      mechanical obstruction. The clinical presentation and blood parameters excluded
      toxic megacolon and cecal volvulus. As the symptoms persisted, a laparotomy was
      performed on postoperative day 16, which demonstrated ragged tears of the colon
      and cecum. A right hemi-colectomy followed by ileocecal anastomosis was required.
      The pathological examination of surgical specimens excluded inflammatory bowel
      disease and vascular abnormalities. The patient made a good recovery following
      bowel surgery and at latest followup 3.2 years later she had no abdominal
      complaints and an excellent scoliosis correction. Ogilvie's syndrome should be
      included in the differential diagnosis of postoperative ileus in patients
      developing prolonged unexplained abdominal distension and pain after scoliosis
      correction. Early diagnosis and instigation of conservative management can
      prevent major morbidity and mortality due to bowel ischemia and perforation. 

PMID- 23960288
TI  - Conjoined legs: Sirenomelia or caudal regression syndrome?
AB  - Presence of single umbilical persistent vitelline artery distinguishes
      sirenomelia from caudal regression syndrome. We report a case of a12-year-old boy
      who had bilateral umbilical arteries presented with fusion of both legs in the
      lower one third of leg. Both feet were rudimentary. The right foot had a valgus
      rocker-bottom deformity. All toes were present but rudimentary. The left foot
      showed absence of all toes. Physical examination showed left tibia vara. The
      chest evaluation in sitting revealed pigeon chest and elevated right shoulder.
      Posterior examination of the trunk showed thoracic scoliosis with convexity to
      right. The patient was operated and at 1 year followup the boy had two separate
      legs with a good aesthetic and functional results. 

PMID- 23960289
TI  - Spontaneous resolution of postoperative lumbar pseudomeningoceles: A report of
      four cases.
AB  - Pseudomeningocele is an extradural cerebrospinal fluid collection arising from a
      dural defect, that may be congenital, traumatic, or more commonly as a result of
      postoperative complication. Majority of the postoperative pseudomeningoceles
      occurring after lumbar spine surgeries are small and resolve spontaneously.
      However, large pseudomeningoceles are rare and spontaneous resolution of such
      pseudomeningoceles has not been described. We report four cases of postoperative
      large lumbar pseudomeningoceles that presented as asymptomatic soft fluctuant
      swelling over the back which resolved spontaneously. We also reviewed the related
      literatures and operative records of these patients to find the possible
      mechanism of occurrence, their management, prevention, and reasons for
      spontaneous resolution. We conclude that nonoperative management under close
      observation can be employed for asymptomatic postoperative large lumbar
      pseudomeningoceles. Surgical exploration and repair should be reserved for
      symptomatic cases presenting with clinical features of intracranial hypotension,
      worsening neurology, external fistula or infection, thereby avoiding morbidity
      and potential complications associated with surgical treatment. 

PMID- 23960290
TI  - Replantation of a circumferentially degloved ring finger by venous
      arterializations.
AB  - Treatment of ring degloving injuries of the finger is one of the most demanding
      problems in hand surgery. Replantation has been advocated as the best solution if
      the vessels belonging to the degloved skin are not irreversibly destroyed. We
      present a case involving a ring finger with circumferentially avulsed skin.
      Debridement under microscopy showed that the peeled skin did not retain any
      arteries, but did have various superficial veins of good caliber. The
      neurovascular bundles of the finger remained in situ and did not appear to be
      disrupted. The degloved finger survived uneventfully by venous arterialization,
      retaining excellent function and appearance. 

PMID- 23960291
TI  - Posttraumatic osteonecrosis and nonunion of distal pole of scaphoid.
AB  - Posttraumatic osteonecrosis of distal pole of scaphoid is an extremely rare with
      only two reported cases so far. We present a case of a 30-year-old male with a 2
      year-old posttraumatic osteonecrosis and nonunion of distal pole of scaphoid left
      wrist. He presented with complaints of pain and restriction of movements. There
      was no evidence of radiocarpal arthritis. He was managed with open reduction and
      internal fixation with k-wires, supplemented by a pronator quadratus based muscle
      pedicle bone graft. The fracture union was achieved at 6 months. After 2 years,
      he had almost complete range of wrist motion and had returned to his preinjury
      level of functional activity. His MRI (magnetic resonance imaging) scans showed
      evidence of revascularization suggesting successful incorporation of bone graft. 

PMID- 23960292
TI  - Corrigendum.

PMID- 23960293
TI  - Outcomes of osteoporotic trochanteric fractures treated with cement - augmented
      dynamic hip screw.

PMID- 23960294
TI  - Author's reply.

PMID- 23960295
TI  - Outcome of subvastus approach in elderly nonobese patients undergoing bilateral
      simultaneous total knee arthroplasty: A randomized controlled study.

PMID- 23960296
TI  - Author's reply.

PMID- 23960297
TI  - Plastic surgery museum.

PMID- 23960298
TI  - Glimpses of a master.

PMID- 23960299
TI  - Ethics and evidence based research: Is there a conflict?

PMID- 23960300
TI  - Ethics and evidence based research: Is there a conflict?

PMID- 23960301
TI  - Ethical practice of evidence-based medicine: A review for plastic surgeons.
AB  - Last decade has witnessed a spurt in articles focused on the topic of evidence
      based medicine (EBM) and medical ethics. These articles are not only educative,
      but draw attention to the changing scenario of medical practice. Surgeons seem a
      bit less attentive to practice of EBM, more so in the developing world. The theme
      is now percolating in our realm for demonstrable incorporation of EBM in our
      practice, which is allegorical of a good physician and is also likely to become
      demanding legally. In practicing EBM, several conflicts may arise with the
      ethical vows of medicine. However, majority of these conflicting issues have
      germinated from a capitalistic approach to medical practice, where the fear of
      extraneous compulsions dictating prescriptions and procedures in the garb of
      'evidence-based practice' conflicts ethical behaviour. This review shall appraise
      the reader with important definitions of medical ethics, EBM and how to
      incorporate best evidence into ones practice. While, EBM brings objectivity to
      treatment to derive measurable outcomes it should not become regimented or
      metamorphose as a pseudonym for defensive medicine to escalate treatment costs.
      EBM also has several limitations one of which is to place the onus on the
      practicing physician to search for the best evidence and the other is the
      resource constraint of practice in the developing world. How a plastic surgery
      practice could be made to conform to evidence based (EB) procedures is proposed
      as insufficient surgical skills can pose a serious threat to not only the
      practice of EB procedures, but to ethical responsibilities as well. In
      conclusion, it is necessary to incorporate ethical temperance into EB procedures
      to withstand societal, peer and legal pressures of current times. 

PMID- 23960302
TI  - Craniosynostosis.
AB  - Craniosynostosis is a premature pathologic fusion of one or more cranial vault
      sutures that leads to abnormal shape of the skull. The fused sutures lead to
      restricted growth in some areas and compensatory bossing in other areas. The head
      may assume different shapes depending upon the site and timing of the abnormally
      fused suture. The exact cause of this suture pathology is still unknown, but the
      local dura, cranial base and the fibroblast growth factors seem to influence
      this. The diagnosis rests on clinical examination and confirmation is generally
      on the computed tomography scan. The need for surgery is both for cosmetic and
      functional reasons. Many cases may be associated with raised intracranial
      pressure with its attendant deleterious effects on vision and brain. The aim of
      treatment is to increase the cranial volume and reshape the skull. The surgery
      can be safely undertaken around 9-12 months in most of the cases. The
      conventional management is through an open surgical approach; although, some
      centres have claimed impressive results with limited endoscopic techniques in
      selected cases. The review article deals with the aetiopathogenesis, clinical
      presentations and management of the common varieties of craniosynostoses seen in
      the Indian scenario. 

PMID- 23960303
TI  - Evolution of instruments for harvest of the skin grafts.
AB  - BACKGROUND: The harvest of autologous skin graft is considered to be a
      fundamental skill of the plastic surgeon. The objective of this article is to
      provide an interesting account of the development of skin grafting instruments as
      we use them today in various plastic surgical procedures. MATERIALS AND METHODS:
      The authors present the chronological evolution and modifications of the skin
      grafting knife, including those contributions not often cited in the literature,
      using articles sourced from MEDLINE, ancient manuscripts, original quotes,
      techniques and illustrations. RESULTS: This article traces the evolution of
      instrumentation for harvest of skin grafts from free hand techniques to precise
      modern automated methods. CONCLUSIONS: Although skin grafting is one of the basic
      techniques used in reconstructive surgery yet harvest of a uniform graft of
      desired thickness poses a challenge. This article is dedicated to innovators who
      have devoted their lives and work to the advancement of the field of plastic
      surgery.

PMID- 23960304
TI  - Keystone flaps in coloured skin: Flap technology for the masses?
AB  - INTRODUCTION: Viscoelastic properties of skin in coloured ethnic groups are less
      favourable compared to Caucasians for executing Keystone flaps. Keystone flaps
      have so far been evaluated and reported only in Caucasians. The potential of
      Keystone flaps in a coloured ethnic group is yet unknown. AIM: This article
      reviews the experience to reconstruct skin defects presenting in a coloured
      ethnic group, by using Keystone flaps, with a review of existing literature.
      DESIGN: Uncontrolled case series. MATERIALS AND METHODS: This retrospective
      review involves 55 consecutive Keystone flaps used from 2009 to 2012, for skin
      defects in various locations. Patient demographic data, medical history, co
      morbidity, surgical indication, defect features, complications, and clinical
      outcomes are evaluated and presented. RESULTS: In this population group with
      Fitzpatrick type 4 and 5 skin, the average patient age was 35.73. Though 60% of
      flaps (33/55) in the series involved specific risk factors, only two flaps
      failed. Though seven flaps had complications, sound healing was achieved by
      suitable intervention giving a success rate of 96.36%. Skin grafts were needed in
      only four cases. CONCLUSIONS: Keystone flaps achieve primary wound healing for a
      wide spectrum of defects with an acceptable success rate in a coloured skin
      population with unfavorable biophysical properties. By avoiding conventional
      local flaps and at times even microsurgical flaps, good aesthetic outcome is
      achieved without additional skin grafts or extensive operative time. All
      advantages seen in previous studies were verified. These benefits can be most
      appreciated in coloured populations, with limited resources and higher proportion
      of younger patients and unfavorable defects.

PMID- 23960305
TI  - Experience with peroneus brevis muscle flaps for reconstruction of distal leg and
      ankle defects.
AB  - OBJECTIVE: Peroneus brevis is a muscle in the leg which is expendable without
      much functional deficit. The objective of this study was to find out its
      usefulness in coverage of the defects of the lower leg and ankle. PATIENTS AND
      METHODS: A retrospective analysis of the use of 39 pedicled peroneus brevis
      muscle flaps used for coverage of defects of the lower leg and ankle between
      November 2010 and December 2012 was carried out. The flaps were proximally based
      for defects of the lower third of the leg in 12 patients and distally based for
      reconstruction of defects of the ankle in 26 patients, with one patient having
      flaps on both ankles. RESULTS: Partial flap loss in critical areas was found in
      four patients requiring further flap cover and in non-critical areas in two
      patients, which were managed with a skin graft. Three of the four critical losses
      occurred when we used it for covering defects over the medial malleolus. There
      was no complete flap loss in any of the patients. CONCLUSION: This flap has a
      unique vascular pattern and fails to fit into the classification of the
      vasculature of muscles by Mathes and Nahai. The unusual feature is an axial
      vessel system running down the deep aspect of the muscle and linking the
      perforators from the peroneal artery and anterior tibial artery, which allows it
      to be raised proximally or distally on a single perforator. The flap is simple to
      raise and safe for the reconstruction of small-to moderate-sized skin defects of
      the distal third of the tibia and all parts of the ankle except the medial
      malleolus, which is too far from the pedicle of the distally based flap. The
      donor site can be closed primarily to provide a linear scar. The muscle flap
      thins with time to provide a good result aesthetically at the primary defect.

PMID- 23960306
TI  - Tensor fascia latae perforator flap: An alternative reconstructive choice for
      anterolateral thigh flap when no sizable skin perforator is available.
AB  - INTRODUCTION: The anterolateral thigh flap (ALT) is a versatile flap and very
      useful for the reconstruction of different anatomical districts. The main
      disadvantage of this flap is the anatomical variability in number and location of
      perforators. In general, absence of perforators is extremely rare. In literature,
      it is reported to be from 0.89% to 5.4%. If no sizable perforators are found, an
      alternative reconstructive strategy must be considered. Tensor fascia lata (TFL)
      perforator flap can be a good alternative in these cases: Perforator vessels are
      always present, the anatomy is more constant and it is possible to harvest it
      through the same surgical access. The skin island of the flap can be very large
      and can be thinned removing a large part of the muscle allowing its use for
      almost the same indications of the ALT flap. MATERIALS AND METHODS: We report 11
      cases of reconstruction firstly planned with the ALT flap, then converted into
      TFL perforator flap. RESULTS AND CONCLUSION: The result was always satisfactory
      in terms of the donor site morbidity and reconstructive outcome.

PMID- 23960307
TI  - Anthropomorphic and perforator analysis of anterolateral thigh flap in Indian
      population.
AB  - BACKGROUND: Anterolateral thigh (ALT) flap is one of the most common flaps in the
      reconstruction armamentarium of plastic surgeons, but there is no published data
      about the flap characteristics in the Indian population. The aim of this study is
      to analyse the anthropomorphic characteristics of the ALT flap and the perforator
      details in Indian population. MATERIALS AND METHODS: ALT flap details were
      studied in 65 patients of Indian origin comprising 45 males and 20 females. The
      study period is from August 2011 to July 2012. A prospective database of the
      Doppler findings, perforator and pedicle details and the flap morphology were
      maintained. The variables are analysed by using the SPSS, PASW statistics 18
      software IBM((r)). RESULTS: In nearly 75% of cases, the perforator was found
      within 4 cm of the pre-operative Doppler markings. The percentage of
      musculocutaneous and septocutaneous perforators was 61.8% and 38.2% respectively.
      The pedicle variation was found in 6 cases (9.23%). The average thickness of the
      thigh skin in Indians is similar to the western people, but thicker than the
      other Asian people. Flap thinning was performed in nine patients without any
      major complications. CONCLUSION: The perforator details and type in the Indian
      population are similar to the published reports from other parts of the world. We
      advise pre-operative Doppler examination in possible cases. The variation in
      pedicle anatomy should not be overlooked to avoid complications. The thickness of
      subcutaneous tissue of the flap is higher in Indians, but still can be safely
      thinned. The data of this study will serve as a guide for the ALT flap
      characteristics in Indian patients.

PMID- 23960308
TI  - Anatomical study of terminal peroneal artery perforators and their clinical
      applications.
AB  - INTRODUCTION: Peroneal artery gives off plenty of perforators that pass through
      fascial septum to supply skin and tenosynovium of peroneal muscles. AIM: The aim
      of this study was to study the anatomical basis of perforators from terminal part
      of peroneal artery axiality and to make use of this knowledge in reconstructing
      defects of posterior heel with the advantage of reducing the morbidity of
      conventional flaps. MATERIALS AND METHODS: Our study was conducted at Department
      of Plastic surgery, Madras Medical College and Rajiv Gandhi Government General
      Hospital, India. We have carried out eleven cadaver dissections (from six
      cadavers-four fresh cadavers and two preserved cadavers) and delineated all
      septocutaneous and septosynovial perforators of distal peroneal axis and studied
      their relation with short saphenous vein (SSV) and sural nerve. Using this
      anatomical knowledge we have fashioned perforator based flaps in 13 patients
      (three propeller, four V-Y advancement, six tenosynovial flaps) for
      reconstruction of defects over tendo achilles and pericalcaneal region. RESULTS:
      In all cases, SSV and sural nerve were preserved and donor site was closed
      primarily. No total flap loss was noted. CONCLUSION: Perforator based flaps from
      distal most part of peroneal artery provide a good and reliable method for
      reconstruction of pericalcaneal and tendo achilles region defects with
      preservation of SSV and sural nerve. It also avoids contour deformity of the
      grafted donor site of the classical lateral calcaneal artery axial flap.

PMID- 23960309
TI  - Tadalafil significantly reduces ischemia reperfusion injury in skin island flaps.
AB  - INTRODUCTION: Numerous pharmacological agents have been used to enhance the
      viability of flaps. Ischemia reperfusion (I/R) injury is an unwanted, sometimes
      devastating complication in reconstructive microsurgery. Tadalafil, a specific
      inhibitor of phosphodiesterase type 5 is mainly used for erectile dysfunction,
      and acts on vascular smooth muscles, platelets and leukocytes. Herein, the
      protective and therapeutical effect of tadalafil in I/R injury in rat skin flap
      model is evaluated. MATERIALS AND METHODS: Sixty epigastric island flaps were
      used to create I/R model in 60 Wistar rats (non-ischemic group, ischemic group,
      medication group). Biochemical markers including total nitrite, malondialdehyde
      (MDA) and myeloperoxidase (MPO) were analysed. Necrosis rates were calculated and
      histopathologic evaluation was carried out. RESULTS: MDA, MPO and total nitrite
      values were found elevated in the ischemic group, however there was an evident
      drop in the medication group. Histological results revealed that early
      inflammatory findings (oedema, neutrophil infiltration, necrosis rate) were
      observed lower with tadalafil administration. Moreover, statistical significance
      (P < 0.05) was recorded. CONCLUSIONS: We conclude that tadalafil has beneficial
      effects on epigastric island flaps against I/R injury.

PMID- 23960310
TI  - Microvascular free flap reconstruction for head and neck cancer in a resource
      constrained environment in rural India.
AB  - INTRODUCTION: Reconstruction with free flaps has significantly changed the
      outcome of patients with head and neck cancer. Microsurgery is still considered a
      specialised procedure and is not routinely performed in the resource-constrained
      environment of certain developing parts of India. MATERIALS AND METHODS: This
      article focuses on the practice environment in a cancer clinic in rural India.
      Availability of infrastructure, selection of the case, choice of flap, estimation
      of cost and complications associated with treatment are evaluated and the merits
      and demerits of such an approach are discussed. RESULTS: We performed 22 cases of
      free flaps in a six-month period (2008-2009). Majority (17) of the patients had
      oral cancer. Seven were related to the tongue and eight to the buccal mucosa.
      Radial forearm free flap (RFF: 9) and anterolateral thigh flap (ALT: 9) were the
      most commonly used flaps. A fibula flap (1) was done for an anterior mandible
      defect, whereas a jejunum free flap (1) was done for a laryngopharyngectomy
      defect. There were six complications with two re-explorations but no loss of
      flaps. CONCLUSION: Reconstruction with microvascular free flaps is feasible in a
      resource-constrained setup with motivation and careful planning.

PMID- 23960311
TI  - Is there an optimal resting velopharyngeal gap in operated cleft palate patients?
AB  - CONTEXT: Videofluoroscopy in operated cleft palate patients. AIMS: To determine
      the existence of an optimal resting velopharyngeal (VP) gap in operated cleft
      palate patients. SETTINGS AND DESIGN: A retrospective analysis of lateral view
      videofluoroscopy of operated cleft palate patients. MATERIALS AND METHODS: A
      total of 117 cases of operated cleft palate underwent videofluoroscopy between
      2006 and 2011. The lateral view of videofluoroscopy was utilised in the study. A
      retrospective analysis of the lateral view of videofluoroscopy of these 117
      patients was performed to analyse the resting VP gap and its relationship to VP
      closure. STATISTICAL ANALYSIS USED: None. RESULTS: Of the 117 cases, 35 had a
      resting gap of less than 6 mm, 34 had a resting gap between 6 and 10 mm and 48
      patients had a resting gap of more than 10 mm. CONCLUSIONS: The conclusive
      finding was that almost all the patients with a resting gap of <6 mm (group C)
      achieved radiological closure of the velopharynx with speech; thus, they had the
      least chance of VP insufficiency (VPI). Those patients with a resting gap of >10
      mm (group A) did not achieve VP closure on phonation, thus having full-blown VPI.
      Therefore, it can be concluded that the ideal resting VP gap is approximately 6
      mm so as to get the maximal chance of VP closure and thus prevent VPI.

PMID- 23960312
TI  - Sentinel lymph node biopsy for cutaneous melanoma: a 6 years study.
AB  - BACKGROUND: The aim of this study was to evaluate the results of sentinel lymph
      node biopsy (SLNB) in cutaneous melanoma at our institution. MATERIALS AND
      METHODS: 128 patients with primary cutaneous melanoma who underwent SLNB between
      April, 2004, and August, 2010 were studied. Univariate and multivariate analysis
      was performed to explore the effect of variables on mortality and sentinel node
      status. Survival analysis was performed using the Kaplan-Meier approach. RESULTS:
      Positive SLNB were detected in 35 (27.3%) of 128 cases. Mean Breslow depths were
      3.7 mm for SLNB positive patients and 1.99 mm for SLNB negative patients. False
      negative rate was 1%. The recurrence rate was 40% for positive patients and 6.5%
      for negative patients (odds ratio 9.7 [confidence interval 95 % 3.3-28.1]). 33
      patients (29%) had an ulcerated melanoma, 12 (10.5%) in the positive group and 21
      (18.5%) in the negative group. The disease recurred in a 48.5% of patients with
      ulcerated melanoma, but only in a 2.5% of patients with non-ulcerated melanoma.
      Upon multivariate analysis, only Breslow thickness (P = 0.005) demonstrate
      statistically significance for SLNB status. Multivariate analysis for
      clinicopathologic predictors of death demonstrate statistically significance for
      Breslow thickness (P = 0.020), ulceration (P = 0.030) and sentinel node status (P
      = 0.020). CONCLUSIONS: This study confirms that the status of the sentinel node
      is a strong independent prognostic factor with a higher risk of death and lower
      survival. Patients with ulcerated melanoma are more likely to develop recurrence,
      and also higher risk of death than patients with non-ulcerated melanoma.

PMID- 23960314
TI  - Vascular Birthmarks - Need a conceptual change in their understanding and
      managemnt.

PMID- 23960313
TI  - Surgical management of scalp arterio-venous malformation and scalp venous
      malformation: An experience of eleven cases.
AB  - AIMS: Scalp arterio-venous malformation (AVM) and scalp venous malformation (SVM)
      are rare conditions that usually need surgical treatment. Here, we have reported
      our experience of the surgical management of such lesions with a short review of
      the literature. MATERIALS AND METHODS: In this prospective study, 11 patients
      with scalp AVM and SVM, who underwent surgical excision of lesion in our hospital
      from 2006 to 2012, were included. All suspected high-flow AVM were investigated
      with the selective internal and external carotid digital subtraction angiogram
      (DSA) +/- computed tomography (CT) scan of brain with CT angiogram or magnetic
      resonance imaging (MRI) of brain with MR angiogram, and all suspected low-flow
      vascular malformation (VM) was investigated with MRI of brain + MR angiogram.
      Eight were high-flow and three were low-flow VM. RESULTS: All lesions were
      successfully excised. Scalp cosmetic aspects were acceptable in all cases. There
      was no major post-operative complication or recurrence till last follow-up.
      CONCLUSIONS: With preoperative appropriate surgical planning, scalp AVM and SVM
      can be excised without major complication.

PMID- 23960315
TI  - Haemangiomas and venous malformations of the head and neck: A retrospective
      analysis of endovascular management in 358 patients.
AB  - BACKGROUND: Haemangioma (HM) and venous malformations of the head and neck are
      formidable lesions as they cause cosmetic deformity and psychological problems.
      Their surgical excision is difficult and fraught with problems like operative
      blood loss, incomplete excision, disfigurement and recurrence. Endovascular
      techniques like sclerotherapy and embolization are increasingly being used in the
      treatment of these difficult lesions. OBJECTIVES: This study was undertaken to
      analyse the efficacy and safety of endovascular techniques in the treatment of HM
      and slow flow vascular malformations. MATERIALS AND METHODS: We retrospectively
      reviewed the records and clinical photographs of 358 patients of HM and slow flow
      vascular malformations treated in our institute by endovascular approach over a
      15 year period. Pre- and post-treatment photographs were compared and outcomes
      categorized as complete resolution (>90% reduction), considerable reduction (60
      90% reduction), partial reduction (20-60% reduction) and no change (<20%
      reduction). RESULTS: Complete resolution of the lesion was seen in 30% of the
      patients while 50% patients showed considerable reduction of the swelling.
      Complications occurred in 6.4% of patients. CONCLUSION: We conclude that
      sclerotherapy is an effective and safe treatment modality for these lesions and
      may be considered as the primary modality in the treatment of these challenging
      lesions.

PMID- 23960316
TI  - Use of body and beard donor hair in surgical treatment of androgenic alopecia.
AB  - OBJECTIVES: Follicular unit transplant is a widely used surgical treatment for
      androgenic alopecia. However, for patients with extensive hair loss (Norwood 5
      and above), scalp donor hair are not sufficient to cover all areas of baldness.
      This study aims to assess suitability of beard and body donor hair when
      transplanted to the scalp. MATERIALS AND METHODS: In 35 male patients having
      varying degrees of androgenic alopecia, body and beard donor hair were extracted
      by follicular unit extraction method (under local anesthesia). They were
      transplanted in different locations of the scalp. Follow-up was carried out at
      various intervals (6 months to 2 years). The hairs were observed for colour, curl
      and calibre. RESULTS: In all the patients, there was no change in the colour,
      curl or calibre of the transplanted body/beard hair. They maintained the same
      characteristics as in their original location. CONCLUSION: Body and beard hair
      can be used as additional donor resource for treating androgenic alopecia. These
      hairs, however, do not change their colour, curl, and shaft diameter (calibre).
      Thus, proper planning is a must when using the different types of donor hair for
      transplanting.

PMID- 23960318
TI  - Rare case of nasolacrimal duct opening into face.
AB  - Congenital anomaly of nasolacrimal duct is mostly obstructive in nature or is
      seen in oblique facial clefts. Nasolacrimal duct drain into the inferior meatus
      in the nose in a normally developed face. We report a rare case of aberrant
      opening of distal end of nasolacrimal duct into the external skin lateral to the
      ala of nose in an adult patient. The only case reported so far was in an infant.
      The patient is a 22 year young male presenting with an opening lateral to the
      left ala of nose with recurrent discharge and conjunctivitis of left eye. The
      embryology is also discussed. 

PMID- 23960317
TI  - Reconstruction of segmental defects of Achilles tendon: Is it a must in infected
      complex defects?
AB  - Loss of Achilles tendon combined with overlying soft tissue loss is a challenging
      problem. Multiple techniques like tendon graft with coverage by soft tissue flap
      or composite flaps have been used. All these options are technically demanding.
      Reports do exist whereby muscle flaps bridging the defect used as cover in course
      of time could transmit the tendon force across the defect. We are presenting a
      case where a free gracilis muscle flap used to cover the soft tissue defect at
      the Achilles tendon at 2 years follow up provided stable cover and produced
      active function of the Achilles tendon allowing the patient to stand tip toe.
      Mechanism of its action has been analysed by MRI and M-mode ultrasound. While in
      primary Achilles tendon injury reconstruction is still the recommended option, in
      complex situations mere filling of the gap with the flap without formal
      reconstruction of the tendon could give good functional outcome. This technique
      can be used in demanding situations. 

PMID- 23960319
TI  - Gluteal flap for omphalocele repair in a case of epigastric heteropagus: A novel
      approach for surgical management.
AB  - Epigastric heteropagus is an extremely rare congenital anomaly, in which there is
      asymmetrical conjoined twinning, with the parasitic twin attached to the
      epigastrium. A 2-day-old male, with epigastric heteropagus and omphalocele, was
      operated in our institution. After excision of the parasitic twin, omphalocele
      was covered with a gluteal skin flap available from the parasitic twin. Post
      operative course was uneventful, except for infection along the edges of the skin
      flaps, which was managed conservatively. Only 44 cases of epigastric heteropagus
      twins have been reported previously in world literature. We present a novel
      surgical approach for the repair of the omphalocele in a case of epigastric
      heteropagus twins, probably the 45(th) case to be reported in the world
      literature. 

PMID- 23960320
TI  - Life threatening deep scald burns in a neonate: A rare case report.
AB  - Domestic burns in neonate are rare in literature. Neonates are high risk for
      burns because of their thin and fragile skin, fluid overload or dehydration as
      the fluid balance range is small and immature immune system leading to
      septicaemia. Neonates are not small adults, owing to their different
      physiological response makes the management of neonates challenging as the
      clinical signs are different from the adults and the resuscitation protocols or
      end points are also different. We present a case of 11 days old neonate, who
      sustained 51% scald burns when the hot water bag being used by her mother
      accidentally burst, the youngest reported case of domestic scald burns with such
      high percentage. The baby was managed by fluid resuscitation, antibiotics,
      dressings, ventilatory support for septicaemia and subsequently homograft
      application. The neonate was discharged with completely healed areas after 35
      days of burns and is on regular follow up and no complications have been
      observed. 

PMID- 23960321
TI  - Retrograde vascularisation of fibula free flap in composite oro-mandibular
      reconstruction.
AB  - We present a case of composite oromandibular reconstruction with fibula free flap
      in which the vascularity to the flap was established in a retrograde direction
      through the distal end of the peroneal pedicle vessels. The flap was initially
      designed in such a way so as to anastomose with superior thyroid artery. However
      after initial good flow, the superior thyroid artery flow became insufficient.
      Therefore, an attempt was made to vascularise the flap by anastomosing the distal
      end of peroneal vessels with the facial artery and a tributary of the internal
      jugular vein so that the flap was perfused in a retrograde direction. This was
      successful and the retrograde flow was adequate to ensure flap survival. We
      believe this to be the first successful case of reverse vascular flow reported
      for composite oromandibular reconstruction with the fibula free flap. 

PMID- 23960322
TI  - Management of bi-canalicular block: A novel technique.
AB  - Medial canthal dystopia with canalicular obstruction is a common presentation
      following injury to the medial canthal region. Conjunctivodacryocystorhinostomy
      with Lester's Jones tube is considered as the standard treatment in such cases.
      Alternatively, these patients can be managed by retrograde intubation
      dacryocystorhinostomy with medial canthoplasty. We herein describe the
      modification of retrograde bicanalicular intubation, combined with medial
      canthoplasty (monopedicle flap) which gives good cosmetic results. 

PMID- 23960323
TI  - Giant median nerve in bilateral carpal tunnel syndrome.
AB  - We introduce a middle age healthy man with sequential bilateral carpal tunnel
      syndrome. At the surgery, we encountered a wide median nerve in both wrists.
      Although enlargement of median nerve in carpal tunnel has been well documented,
      25 mm width of the nerve is a rare scene, underscoring that leaving the nerve
      under the unyielding pressure would lead to a fibrous atrophic median nerve. 

PMID- 23960324
TI  - Penile replantation.
AB  - Penile amputation is rare and hence the paucity of experience and publication. We
      present our case of self-inflicted penile amputation, which was successfully
      managed with microsurgical replantation, with relevant literature review. 

PMID- 23960325
TI  - A simple and effective way of maintaining the microvascular field clean and dry
      during anastomosis.
AB  - During microvascular anastomosis, it is important to maintain the microsurgical
      field irrigated yet dry so as to achieve a good view of the vessels for
      approximation. In this method, an infant feeding tube (size 4), with its tip
      sandwiched between layers of dry gauze and a surgical glove component placed in
      the anastomotic field and the other end connected to a suction apparatus, is used
      to maintain the microsurgical field free from flooding. It also has the
      additional advantage of providing a stable platform for microvascular
      anastomosis. 

PMID- 23960326
TI  - Absence of the palmaris longus is a warning sign for avoiding the superficial
      ulnar artery 'trap'.

PMID- 23960327
TI  - Commentary: Unilaterally absent palmaris longus: A golden opportunity.

PMID- 23960328
TI  - Rare tumours of the hard palate.

PMID- 23960329
TI  - Deepithelialization of breast in reduction mammoplasty using cable tie as breast
      tourniquet.

PMID- 23960330
TI  - A rare case of epidermolysis bullosa.

PMID- 23960331
TI  - Mandibular distraction in a 75-day-old child with severe Pierre Robin sequence.

PMID- 23960332
TI  - A very large Marjolin's ulcer on back without lymph node metastasis.

PMID- 23960333
TI  - Lobster claw syndrome: A rare entity.

PMID- 23960334
TI  - Botulinum toxin in hemifacial spasm: Revisited.

PMID- 23960335
TI  - A novel technique for piercing of ear lobule suited to Indian subcontinent.

PMID- 23960336
TI  - Diet, wound healing and plastic surgery.

PMID- 23960337
TI  - Basics of kidney biopsy: A nephrologist's perspective.
AB  - The introduction of the kidney biopsy is one of the major events in the history
      of nephrology. Primary indications of kidney biopsy are glomerular
      hematuria/proteinuria with or without renal dysfunction and unexplained renal
      failure. Kidney biopsy is usually performed in prone position but in certain
      situations, supine and lateral positions may be required. Biopsy needles have
      changed with times from Vim-Silverman needle to Tru-cut needle to spring-loaded
      automatic gun. The procedure has also changed from blind bedside kidney biopsy to
      ultrasound marking to real-time ultrasound guidance to rarely computerized
      tomography guidance and laparoscopic and open biopsy. In very specific
      situations, transjugular kidney biopsy may be required. Most of the centers do
      kidney biopsy on short 1-day admission, whereas some take it as an outdoor
      procedure. For critical interpretation of kidney biopsy, adequate sample and
      clinical information are mandatory. Tissue needs to be stained with multiple
      stains for delineation of various components of kidney tissue. Many consider that
      electron microscopy (EM) is a must for all kidney biopsies, but facilities for EM
      are limited even in big centers. Sophisticated tests such as immunohistochemistry
      and in-situ hybridization are useful adjuncts for definitive diagnosis in certain
      situations. 

PMID- 23960339
TI  - The short-term impact of protocol biopsies in a live-related renal transplant
      program using tacrolimus based immunosuppression.
AB  - The aim of the study was to assess the impact of protocol biopsies in a live
      related renal transplant program using tacrolimus-based immunosuppression in the
      short term. Eighty-three live-related transplant recipients were randomly
      allocated to protocol biopsy group (Group I, n = 40) and a control group (Group
      II, n = 43). Other immunosuppressants in these groups consisted of either
      mycophenolate mofetil or azathioprine and steroids. Protocol biopsies were
      conducted in biopsy group at 1, 6, and 12 months post-transplant. The non-biopsy
      group was followed by serial serum creatinine and biopsies in them were conducted
      as and when clinically indicated. Both groups were analyzed at 12 months with
      respect to graft function and survival. The two groups were similar with respect
      to age, number of dialysis pre-operatively, tacrolimus levels, induction therapy,
      donor age, and donor glomerular filtration rate. Forty protocol biopsies were
      conducted at 1 month, 31 at 6 months, and 26 at 12 months. The prevalence of sub
      clinical rejection at 1, 6, and 12 months in these biopsies was 17.5%, 11.2%, and
      10.3%, respectively. The prevalence of calcineurin inhibitor toxicity during same
      period was 15%, 15.5%, and 14.4%, respectively. The cumulative rejection rate in
      Group I and Group II at 12-month follow-up was 10.3% and 11.3% (P = 0.78),
      respectively, and cumulative calcineurin inhibitor toxicity at 12 months was
      14.4% and 9.3% (P = 0.59), respectively, were not statistically significant.
      There was no difference in graft survival and function at 1 year. Protocol
      biopsies have a limited role in a well-matched renal transplant program with
      tacrolimus-based immunosuppression in the short term. However, the long-term
      impact of protocol biopsies needs further evaluation. 

PMID- 23960340
TI  - No detection of Helicobacter pylori in atherosclerotic plaques in end stage renal
      disease patients undergoing kidney transplantation.
AB  - Chronic infection known to be a predisposing factor for the development of
      atherosclerosis. Several studies have found a possible role of Helicobacter
      pylori in the pathogenesis of atherosclerosis. The aim of this study was to
      investigate the presence of H. pylori in atherosclerotic plaques in iliac
      arteries in 25 end stage renal disease (ESRD) patients undergoing kidney
      transplantation. Esophagogastroduodenoscopy was performed in all patients before
      transplantation. Biopsy specimens obtained from gastric antrum were sent for
      pathologic evaluation. Gastric H. pylori infection was confirmed by microscopic
      assessment and rapid urease test. Arterial specimens were obtained from iliac
      arteries during kidney transplantation. Presence of H. pylori DNA in
      atherosclerotic plaques and healthy vessel samples was evaluated by the
      polymerase chain reaction (PCR). The mean age of patients was 44.1 +/- 22.6
      years. Risk factors in patients with atherosclerosis were hypertension (68%),
      diabetes mellitus (20%), hyperlipidemia (20%), positive family history (16%).
      Atherosclerotic plaques were found in 21 (84%) patients. PCR analysis did not
      detect H. pylori in any case. There was a significant relationship of
      atherosclerosis with hypertension (P = 0.006) but not with diabetes mellitus and
      hyperlipidemia (P = 0.5). There was no significant relationship between
      atherosclerosis and gastric H. pylori infection (P = 0.6). This study revealed no
      association between the presence of H. pylori as a pathogen of vessel walls and
      atherosclerosis in ESRD. 

PMID- 23960341
TI  - Melatonin improves sleep quality in hemodialysis patients.
AB  - Disturbed sleep is common in end-stage renal disease (ESRD). Exogenous melatonin
      has somniferous properties in normal subjects and can improve sleep quality (SQ)
      in several clinical conditions. Recent studies have shown that melatonin may play
      a role in improving sleep in patients undergoing dialysis. The goal of the
      present study was to assess the effect of exogenous melatonin administration on
      SQ improvement in daytime hemodialysis patients. Lipid profile and the required
      dose of erythropoietin (EPO) are also reported as secondary outcomes. In a 6-week
      randomized, double-blind cross-over clinical trial, 3 mg melatonin or placebo was
      administered to 68 patients at bedtime. A 72-h washout preceded the switch from
      melatonin to placebo, or vice versa. SQ was assessed by the Pittsburgh sleep
      quality index (PSQI). Sixty-eight patients completed the study protocol and were
      included in the final analysis. Melatonin treatment significantly improved the
      global PSQI scores (P < 0.001), particularly subjective SQ (P < 0.001), sleep
      efficiency (P = 0.005) and sleep duration (P < 0.001). No differences in sleep
      latency and daytime sleepiness were observed. Melatonin also increased the high
      density lipoprotein (HDL) cholesterol (P = 0.003). The need for EPO prescription
      decreased after melatonin treatment (P < 0.001). We conclude that melatonin can
      improve sleep in ESRD. The modest increase in HDL cholesterol and decrease in the
      EPO requirement are other benefits associated with this treatment. 

PMID- 23960342
TI  - On dialysis, sleep and melatonin.

PMID- 23960343
TI  - Efficacy and safety of oral doxercalciferol in the management of secondary
      hyperparathyroidism in chronic kidney disease stage 4.
AB  - This study was carried out to evaluate the efficacy and safety of doxercalciferol
      as therapy for secondary hyperparathyroidism (SHPT) in patients with chronic
      kidney disease (CKD) stage 4 in a prospective clinical trial. A total of 35 CKD-4
      patients who had a baseline parathyroid hormone (iPTH) >150 pg/mL and had not
      received any vitamin D analog in the preceding 8 weeks were followed up at
      intervals of 6 weeks for 18 weeks on oral therapy with doxercalciferol. The
      starting dose was 1.5 MUg/day, and the dose was increased in steps of 1 MUg/day
      if iPTH did not decrease by at least 30% on the subsequent visit. Doxercalciferol
      was stopped temporarily if low iPTH (<70 pg/mL), hypercalcemia (>10.7 mg/dL), or
      severe hyperphosphatemia (>8.0 mg/dL) occurred, and was restarted at a lower dose
      on reversal of these abnormalities. Calcium acetate was the only phosphate binder
      used. Mean iPTH decreased by 35.4 +/- 4.4% from 381.7 +/- 31.3 pg/mL to 237.9 +/-
      25.7 pg/mL (P < 0.001). The proportion of patients who achieved 30% and 50%
      suppression of iPTH levels was 83% and 72%, respectively. Mean serum calcium,
      phosphorus, and calcium-phosphorus product values did not differ significantly
      from the baseline values. Four, two, and nine patients developed hypercalcemia,
      severe hyperphosphatemia, and high CaxP (>55), respectively. Almost all patients
      recovered to an acceptable level within 2 weeks of stopping doxercalciferol and
      adjusting the phosphate binder dose. In all, 21 patients required temporary
      stoppage of therapy. Most of them were restarted on therapy at a reduced dose
      during the study. It can, therefore, be concluded that doxercalciferol is
      effective in controlling SHPT in CKD-4 patients with an acceptable risk of
      hyperphosphatemia and hypercalcemia. 

PMID- 23960344
TI  - "Ico-Alone" single nocturnal exchange to initiate peritoneal dialysis in patients
      with residual renal function-Five year, single centre experience.
AB  - We analyzed the outcome of incremental dialysis with single nocturnal icodextrin
      exchange peritoneal dialysis (PD) as the initial treatment for end-stage kidney
      failure in patients who have significant residual renal function. All adult
      patients opting for PD as renal replacement therapy, having residual renal
      function, and urinary KT/V of 1.0 were offered incremental dialysis with single
      nocturnal icodextrin exchange as initial treatment. Adequacy of dialysis was
      calculated at 1, 3, and 6 months and then 6 monthly. Patients were shifted to
      conventional PD if short of adequacy or if clinically indicated. Median period on
      "Ico-alone," peritonitis, exit site infection rates, and patient survival, while
      on this protocol, were calculated. These outcomes were compared with the cohort
      of contemporary patients on conventional PD. Thirteen patients were initiated on
      "Ico-alone" dialysis between October 2006 and October 2011. The baseline
      characteristics were similar when compared with cohort of conventional PD
      patients, except urine volume, which was more in "Ico-alone" group (1265 +/- 316
      vs. 551 +/- 504, P = 0.000). Total KT/V at 3 months (1.63 +/- 0.6 vs. 1.7 +/-
      0.2, P = 0.6) and at 1 year (1.64 +/- 0.5 vs. 1.53 +/- 0.3, P = 0.6) was similar
      to the cohort of conventional PD patients. Median period on "Ico-alone" was 9.6
      months. Peritonitis rate was 1 episode in 56.22 vs 25.29 patient-months and exit
      site infection was 1 episode in 56.2 vs 189.71 patient-months in "Ico-alone" and
      conventional group, respectively. Patient survival was 42.84 months in "Ico
      alone" vs 25.29 months in conventional dialysis (P = 0.01). In conclusion, single
      icodextrin exchange offers adequate dialysis in patients with residual renal
      function (KT/V = 1) for a median period of 9 months. 

PMID- 23960345
TI  - Allopurinol for prevention of progression of kidney disease with hyperuricemia.
AB  - Hyperuricemia is associated with hypertension and progressive chronic renal
      disease. This is a retrospective cohort study in chronic kidney disease (CKD)
      patients with hyperuricemia from 1998 to 2008. Patients were divided into two
      groups: treatment group who received allopurinol in a dose of 100 mg/day and the
      other group remained untreated. Clinical, hematologic, biochemical parameters and
      outcome were measured at baseline and 6 months, 1 year, and 2 years of treatment.
      A total of 183 patients were enrolled. Mean age of the allopurinol group was
      50.15 +/- 14.42 years and control group was 53.23 +/- 13.86 years. Male-female
      ratios were 2.57:1 and 2.21:1 for the treatment and control groups, respectively.
      Baseline characteristics and the laboratory parameters were similar in both
      groups. Patients who received allopurinol had lower blood pressure at 6 months, 1
      year, and 2 years when compared to baseline. There was a significant decrease in
      the serum uric acid (UA) levels in the treatment group at the end of 6 months, 1
      year, and 2 years with respect to base line. An inverse correlation as noted
      between serum UA levels and the estimated glomerular filtration rate at 6 months,
      1 year, and 2 years. Allopurinol treatment decreases blood UA levels and is
      associated with better blood pressure control and decreased progression of renal
      disease in CKD patients with hyperuricemia. 

PMID- 23960346
TI  - Spectrum of lymphoproliferative disorders following renal transplantation in
      North India.
AB  - Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized, but
      uncommon complication of organ transplantation. This study was a retrospective
      analysis of 2000 patients who underwent renal transplantation over a period of 30
      years (1980-2010). Forty malignancies were diagnosed in 36 patients. Of these, 29
      patients (1.45%) had PTLD (7 females, 22 males) accounting for 72.5% of all
      malignancies after transplantation. Twenty-two (75.8%) developed non-Hodgkin
      lymphoma and seven patients (24.2%) had myeloma. Diagnosis was made by biopsy of
      the involved organ in 21 patients (72.4%) and aspiration cytology in five
      patients (17.2%). In three patients, the diagnosis was made only at autopsy. Mean
      age at the time of diagnosis of PTLD was 41.9 years (range 21-69 years). Time
      interval from transplantation to the diagnosis of PTLD ranged from 3 months to
      144 months with a median of 48 months. Only five patients (17.2%) developed PTLD
      within a year of transplantation. Twelve patients developed PTLD 1-5 years and 12
      patients 5-10 years after transplantation. Organ involvement was extra nodal in
      18 patients (82%). Thirteen (59%) patients had disseminated disease and nine
      (41%) had localized involvement of a single organ (brain-3, liver-1, allograft-1,
      perigraft node-1, retroperitoneal lymph nodes-3). Infiltration of the graft was
      noted in two patients. Patients with myeloma presented with backache,
      pathological fracture, unexplained anemia or graft dysfunction. PTLD was of B
      cell origin in 20 cases (70%). CD 20 staining was performed in 10 recent cases,
      of which 8 stained positive. Of the 26 patients diagnosed during life, 20 (69%)
      died within 1 year of diagnosis despite therapy. In conclusion, PTLD is
      encountered late after renal transplantation in the majority of our patients and
      is associated with a dismal outcome. The late onset in the majority of patients
      suggests that it is unlikely to be Epstein Barr virus related. 

PMID- 23960347
TI  - Acute renal failure as an initial manifestation of acute lymphoblastic leukemia.
AB  - Acute lymphoblastic leukemia (ALL) is the most common malignancy in children.
      Acute renal failure is a well-recognized complication of ALL after initiation of
      chemotherapy. Renal failure as the primary manifestation of ALL is rare. Here, we
      report three children who presented with acute renal failure and hyperuricemia
      and were subsequently diagnosed to have ALL. 

PMID- 23960348
TI  - Type IV renal tubular acidosis following resolution of acute kidney injury and
      disseminated intravascular coagulation due to hump-nosed viper bite.
AB  - Hump-nosed viper bite can cause acute kidney injury (AKI) and disseminated
      intravascular coagulation. In some patients, it can cause chronic kidney disease
      necessitating life-long renal replacement therapy. Lack of effective antivenom
      makes the management of these patients difficult. A 51-year-old Sri Lankan male
      was admitted with AKI and disseminated intravascular coagulation following a hump
      nosed viper bite. He made a complete recovery with blood product support and
      hemodialysis. Renal biopsy was performed as his renal recovery was prolonged
      which revealed patchy tubular atrophy and interstitial inflammation suggestive of
      subacute interstitial nephritis. Later, he presented with hyperkalemic paralysis
      and acidosis. A diagnosis of late onset type 4 renal tubular acidosis was made
      and he responded well to a course of fludrocortisone. 

PMID- 23960349
TI  - Acute oxalate nephropathy due to 'Averrhoa bilimbi' fruit juice ingestion.
AB  - Irumban puli (Averrhoa bilimbi) is commonly used as a traditional remedy in the
      state of Kerala. Freshly made concentrated juice has a very high oxalic acid
      content and consumption carries a high risk of developing acute renal failure
      (ARF) by deposition of calcium oxalate crystals in renal tubules. Acute oxalate
      nephropathy (AON) due to secondary oxalosis after consumption of Irumban puli
      juice is uncommon. AON due to A. bilimbi has not been reported before. We present
      a series of ten patients from five hospitals in the State of Kerala who developed
      ARF after intake of I. puli fruit juice. Seven patients needed hemodialysis
      whereas the other three improved with conservative management. 

PMID- 23960350
TI  - Acute renal failure secondary to ingestion of ayurvedic medicine containing
      mercury.
AB  - Several traditional medicines contain potentially toxic heavy metals. Heavy metal
      poisoning is not an uncommon cause of renal damage, although the diagnosis can be
      easily missed. We report a case of chronic ingestion of an ayurvedic medicine
      containing mercury in a 2-year-old girl, resulting in anuric renal failure due to
      acute interstitial nephritis. 

PMID- 23960352
TI  - IgG4 related interstitial nephritis: A case report and review of literature.
AB  - IgG4 interstitial nephritis is a recently described entity. A middle-aged
      gentleman with bilateral parotid enlargement, hepatosplenomegaly and generalized
      lymphadenopathy was referred to us for evaluation of renal failure. He had trace
      proteinuria and large kidneys. Kidney biopsy revealed interstitial nephritis with
      characteristic storiform fibrosis. Immunohistochemistry demonstrated intense
      staining for IgG4-secreting plasma cells in the interstitium. 

PMID- 23960351
TI  - Acute interstitial nephritis due to proton pump inhibitors.
AB  - Proton pump inhibitors (PPI) are commonly prescribed for dyspepsia and acid
      peptic disease. Acute interstitial nephritis (AIN) is an uncommon though
      important side-effect of these classes of drugs. We describe four cases: three
      females and one male. PPIs implicated were pantoprazole in two, omeprazole and
      esomeprazole in one each. AIN developed after an average period of 4 weeks of
      drug therapy. The symptoms were vomiting, loin pain, and oliguria. Minimal
      proteinuria with pyuria were seen and the mean serum creatinine was 4.95 +/- 4
      mg/dl. Two patients required hemodialysis. Renal biopsy showed interstitial
      mononuclear, plasma cell and eosinophilic infiltrates in all cases. PPI was
      stopped and steroids were started in all. Renal recovery was total in two and
      partial in two. A high index of suspicion is required to diagnose PPI induced
      AIN. Renal biopsy for confirmation followed up by prompt steroid therapy results
      in renal functional improvement. 

PMID- 23960353
TI  - Renal disease masquerading as pyrexia of unknown origin.
AB  - Pyrexia of unknown origin is a challenging clinical problem. Infections,
      malignancies, and connective tissue diseases form the major etiologies for this
      condition. We report a case of a 57-year-old diabetic male who presented with
      fever of unknown origin for several months. The course of investigations led to a
      kidney biopsy which clinched the cause of his fever as well as the underlying
      diagnosis. The light microscopy findings of expansile storiform fibrosis with a
      dense inflammatory infiltrate suggested the diagnosis which was confirmed by
      positive staining of Immunoglobulin G4, the dense lympho-plasmacytic infiltrate
      and elevated serum IgG4 concentrations. A course of steroids followed by
      mycophenolate mofetil as maintenance immunosuppression rendered the patient
      afebrile with improvement of renal function. 

PMID- 23960354
TI  - Oxalate nephropathy: An important cause of renal failure after bariatric surgery.
AB  - Obesity is a major public health issue all over the world. Bariatric surgery is
      increasingly becoming popular as a surgical treatment for morbid obesity.
      Nephrologists need to be aware of possible renal complications after bariatric
      surgery. We report a 54-year-old male patient who presented with progressive
      worsening of renal function following a duodenal switch procedure for morbid
      obesity, and he was found to have oxalate nephropathy on renal biopsy. 

PMID- 23960355
TI  - Indigo color urine in hemodialysis patient.

PMID- 23960356
TI  - An unusual cause of acute deterioration in a chronic kidney disease patient.

PMID- 23960357
TI  - Polycythemia in hepatits C seropositive end stage renal disease patients: Role of
      insulin like growth factor 1.

PMID- 23960358
TI  - Congenital mesoblastic nephroma: A rare cause of recurrent hematuria beyond
      infancy.

PMID- 23960359
TI  - Ten year follow up of erythropoietin induced autoimmune pure red cell aplasia.

PMID- 23960360
TI  - Need for parenteral pyridoxine: A clarion call.

PMID- 23960361
TI  - Clinical and radiographic factors influencing the results of revision rotator
      cuff repair.
AB  - PURPOSE: Historically, results of open revision of rotator cuff repair have been
      mixed and often poor. We reviewed the outcomes of revision rotator cuff repair
      with a detailed analysis of clinical and radiographic risk factors in order to
      improve patient selection for this type of surgery. MATERIALS AND METHODS: Thirty
      six patients (37 shoulders) underwent first-time, open revision rotator cuff
      repair between 1995 and 2005. Average follow-up was 7.0 years (range 1-14.9
      years). The tear size was small in 1 shoulder, medium in 8, large in 22 and
      massive in 6. Associations of 29 clinical and radiographic factors with the
      outcomes of pain, motion, and function were assessed. RESULTS: Satisfactory
      outcome occurred in 22 shoulders (59%): An excellent result in 2, a good result
      in 7, and a fair result in 13. Unsatisfactory, poor results occurred in 15. Pain
      was substantially reduced in 25 (68%). Median pain scores decreased to five from
      a pre-operative eight (P = 0.002). Median motion did not change from pre
      operative to post-operative. The chance of a satisfactory outcome and improved
      post-operative motion were associated with males, greater pre-operative motion,
      increased acromial humeral distance, the absence of glenohumeral arthritis, or a
      degenerative re-tear. CONCLUSIONS: Revision rotator cuff repair, although a safe
      operation, with a low re-operative rate, has very mixed overall results. By
      knowing the factors associated with success, surgeons can better counsel patients
      and with this increased knowledge, consider alternative treatment choices.

PMID- 23960362
TI  - An in-vitro study of rotator cuff tear and repair kinematics using single- and
      double-row suture anchor fixation.
AB  - PURPOSE: Double-row suture anchor fixation of the rotator cuff was developed to
      reduce repair failure rates. The purpose of this study was to determine the
      effects of simulated rotator cuff tears and subsequent repairs using single- and
      double-row suture anchor fixation on three-dimensional shoulder kinematics. It
      was hypothesized that both single- and double-row repairs would be effective in
      restoring active intact kinematics of the shoulder. MATERIALS AND METHODS:
      Sixteen fresh-frozen cadaveric shoulder specimens (eight matched pairs) were
      tested using a custom loading apparatus designed to simulate unconstrained motion
      of the shoulder. In each specimen, the rotator cuff was sectioned to create a
      medium-sized (2 cm) tear. Within each pair, one specimen was randomized to a
      single-row suture anchor repair, while the contralateral side underwent a double
      row suture anchor repair. Joint kinematics were recorded for intact, torn, and
      repaired scenarios using an electromagnetic tracking device. RESULTS: Active
      kinematics confirmed that a medium-sized rotator cuff tear affected glenohumeral
      kinematics when compared to the intact state. Single- and double-row suture
      anchor repairs restored the kinematics of the intact specimen. CONCLUSIONS: This
      study illustrates the effects of medium-sized rotator cuff tears and their
      repairs on active glenohumeral kinematics. No significant difference (P >= 0.10)
      was found between the kinematics of single- and double-row techniques in medium
      sized rotator cuff repairs. CLINICAL RELEVANCE: Determining the relative effects
      of single- and double-row suture anchor repairs of the rotator cuff will allow
      physicians to be better equipped to treat patients with rotator cuff disease.

PMID- 23960363
TI  - Management of acute displaced midshaft clavicular fractures using Herbert
      cannulated screw: Technique and results in 114 patients.
AB  - PURPOSE: A new and simple operative technique has been developed to provide
      internal fixation for midshaft clavicle fractures. This involves the use of a
      large fragment Herbert Screw that is entirely embedded within the bone. Screw
      fixation is combined with bone grafting from intramedullary reamings of the
      fracture fragments. The purpose of this report is to assess the outcomes
      following treatment of midshaft clavicular fracture using this method. MATERIALS
      AND METHODS: One hundred and fourteen patients with acute displaced midshaft
      fracture were identified between 2002 and 2007. All patients were followed until
      fracture union. Patients' medical records were reviewed. Disability of the Arm,
      Shoulder, and Hand questionnaire (DASH), and American Shoulder and Elbow Surgeons
      Elbow form (ASES) were posted to all patients. Outcome measures included union
      rate, time to union, implant removal rate, DASH, and ASES scores. RESULTS:
      Patients' median age was 29.5 years (interquartile range, 19-44 years). The most
      common injury mechanism was sports injury (28%). The median time from injury to
      surgery was 5 days (interquartile range, 2-9 days). Union occurred in an average
      of 8.8 weeks. Non-union occurred in three cases (2.6%). The re-operation rate for
      symptomatic hardware prominence screw was 1.7%. The median DASH score was 0.83
      and the median ASES was 100 (n = 35). CONCLUSIONS: Intramedullary fixation using
      cannulated Herbert screw can be used as an effective approach for operative
      management of midshaft clavicular fractures. Using this method, an appropriate
      outcome could be achieved and a second intervention for implant removal could be
      avoided in great majority of cases. LEVEL OF EVIDENCE: Level III.

PMID- 23960364
TI  - Floating shoulders: Clinical and radiographic analysis at a mean follow-up of 11
      years.
AB  - CONTEXT: The floating shoulder (FS) is an uncommon injury, which can be managed
      conservatively or surgically. The therapeutic option remains controversial. AIMS:
      The goal of our study was to evaluate the long-term results and to identify
      predictive factors of functional outcomes. SETTINGS AND DESIGN: Retrospective
      monocentric study. MATERIALS AND METHODS: Forty consecutive FS were included (24
      nonoperated and 16 operated) from 1984 to 2009. Clinical results were assessed
      with Simple Shoulder Test (SST), Oxford Shoulder Score (OSS), Single Assessment
      Numeric Evaluation (SANE), Short Form-12 (SF12), Disabilities of the Arm Shoulder
      and Hand score (DASH), and Constant score (CST). Plain radiographs were reviewed
      to evaluate secondary displacement, fracture healing, and modification of the
      lateral offset of the gleno-humeral joint (chest X-rays). New radiographs were
      made to evaluate osteoarthritis during follow-up. STATISTICAL ANALYSIS USED: T
      test, Mann-Whitney test, and the Pearson's correlation coefficient were used. The
      significance level was set at 0.05. RESULTS: At mean follow-up of 135 months
      (range 12-312), clinical results were satisfactory regarding different mean
      scores: SST 10.5 points, OSS 14 points, SANE 81%, SF12 (50 points and 60 points),
      DASH 14.5 points and CST 84 points. There were no significant differences between
      operative and non-operative groups. However, the loss of lateral offset
      influenced the results negatively. Osteoarthritis was diagnosed in five patients
      (12.5%) without correlation to fracture patterns and type of treatment.
      CONCLUSIONS: This study advocates that floating shoulder may be treated
      conservatively and surgically with satisfactory clinical long-term outcomes.
      However, the loss of gleno-humeral lateral offset should be evaluated carefully
      before taking a therapeutic option.

PMID- 23960365
TI  - Intramedullary nailing of humeral diaphyseal fractures. Is distal locking really
      necessary?
AB  - PURPOSE: Distal interlocking is regarded as an inherent part of the antegrade
      humeral nailing technique, but it exposes both the patient and surgeon to
      radiation, is time consuming, and has a potential risk of damaging neurovascular
      structures. We have presented our technique of diaphyseal humeral nailing without
      any distal interlocking in this paper. MATERIALS AND METHODS: We have presented a
      series of 64 consecutive patients (33 male and 31 female, mean age: 41.5 years)
      with humeral shaft fractures treated with antegrade rigid intramedullary nailing
      without distal interlocking following a strict intra and postoperative protocol.
      According to the AO classification, there were 36 type A fractures, 22 type B,
      and 6 type C. Nails were inserted unreamed or by using limited proximal reaming
      and they were fitted as snuggly as possible into the medullary canal. After
      impaction of the nail into the fossa, we carefully tested rotational stability of
      fixation by checking any potential external rotation when the arm was slightly
      turned externally and left to the gravity forces. We were ready to add distal
      screws, but that was not required in these cases. Follow-up assessment included
      fracture union, complications and failures, and the final clinical outcome at
      minimum 2-year follow-up using the parameters of the constant score. RESULTS: All
      fractures, except two, united between the 4(th) and 5(th) postoperative month. In
      one case, nail was exchanged with plate, and, in another, a larger nail was used
      at a second surgery. Shoulder function according to constant score, at a minimum
      of 2-year follow-up, was excellent or very good in 93.7% of the patients.
      CONCLUSIONS: Provided that some technical issues are followed, the method reduces
      intraoperative time and radiation exposure and avoids potential damage to
      neurovascular structures.

PMID- 23960366
TI  - Reverse shoulder arthroplasty in acute fractures of the proximal humerus: A
      systematic review.
AB  - The indications for surgical intervention in complex fractures of the proximal
      humerus are disputed. In elderly patients with poor bone stock it may be
      impossible to obtain satisfactory fixation of the tuberosities to a
      hemiarthroplasty (HA). In such cases primary insertion of a reverse shoulder
      arthroplasty (RSA) has been suggested. We aimed to review clinical studies
      reporting benefits and harms of RSA in acute fractures. A systematic review. We
      included 18 studies containing 430 RSA in acute fractures. We found no randomized
      clinical trials. Four studies compared outcome after RSA with a historical
      control group of HA. The median constant score was 58 (range 44-68) which is
      comparable to previous reviews of HA in 4-part fractures. Complications included
      dislocation, infection, hematoma, instability, neurological injury, reflex
      sympathetic dystrophy, intraoperative fractures, periprosthetic fractures, and
      baseplate failure. Scapular notching was reported in 11 studies with a median
      value of 25% (range 0-94). Heterogeneity of study designs and lack of primary
      data precluded statistical pooling of data. No high quality evidence was
      identified. Based on the available evidence the use of RSA in acute fractures is
      questionable. The complication rate was high and the clinical implications of
      long term scapular notching are worrying. Randomized studies with long term
      follow up using the latest techniques of tubercular reinsertion in RSA toward HA
      should be encouraged. 

PMID- 23960367
TI  - Arthroscopic fixation with a minimally invasive axillary approach for latissimus
      dorsi transfer using an endobutton in massive and irreparable postero-superior
      cuff tears.
AB  - Arthroscopically assisted latissimus dorsi transfer is a viable option for
      treatment of patients in their 50s to 70s, without arthritis of the glenohumeral
      joint, who suffer from massive rotator cuff tears that are not amendable to
      primary repair due to fatty changes in the muscle tissue, or that have failed
      previous repair attempts. This procedure offers immediate and dramatic pain
      relief and is not as technically demanding as one might think. Understanding and
      respecting the principles of tendon transfer is a key to the success of this
      procedure. 

PMID- 23960368
TI  - What's new in emergencies, trauma and shock? Pellets, rubber bullets, and
      shotguns: Less lethal or not?

PMID- 23960369
TI  - Pattern, presentation and management of vascular injuries due to pellets and
      rubber bullets in a conflict zone.
AB  - BACKGROUND: Rubber bullets and pellet guns are considered non-lethal low-velocity
      weapons. They are used to disperse a mob during street protests. The present
      study was undertaken to analyze the pattern, presentation and management of
      vascular injuries caused by these weapons. PATIENTS AND METHODS: This was a
      prospective study of patients with features of vascular injuries due to pellets
      and rubber bullets from June 2010 to November 2010. All patients with features of
      vascular injuries due to these non-lethal weapons were included in the study.
      Vascular injuries caused by other causes were excluded from the study. RESULTS: A
      total of 35 patients who presented with features of vascular injury during this
      period were studied. All of them were males. The mean age was 22 years. Fifteen
      patients were revascularized primarily, 19 patients needed reverse saphenous vein
      graft and, in one, patient lateral repair was done. There were two mortalities in
      our series. Wound infection was the most common complication. The amputation rate
      was around 6%. CONCLUSION: Pellet and rubber bullets can cause serious life
      threatening injuries. Vascular injury caused by these weapons need no different
      approach than other vascular injuries. Early revascularization and prompt
      resuscitation prevents the loss of limb or life.

PMID- 23960370
TI  - Characteristics of patients that experience cardiopulmonary arrest following
      aortic dissection and aneurysm.
AB  - AIM: The aim of this study is to investigate the characteristics of patients
      experience cardiopulmonary arrest (CPA) in the acute phase following aortic
      dissection and aneurysm (AD). MATERIALS AND METHODS: Patients who were
      transported to this department from January 2005 to December 2010 and
      subsequently diagnosed with AD were included in this study. Patients with
      asymptomatic AD or those with AD that did not develop CPA were excluded. The AD
      was classified into four categories: Stanford A (SA), Stanford B (SB), thoracic
      aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA). The frequency of
      witnessed collapse, gender, average age, past history including hypertension,
      vascular complications and diabetes mellitus, the initial complaint at the timed
      of dissection, initial electrocardiogram at scene, classification of CPA and
      survival ratio were compared among the patient groups. RESULTS: There were 24
      cases of SA, 1 case of the SB, 8 cases of ruptured TAA and 9 cases of ruptured
      AAA. The frequency of males among all subjects was 69%, the average age was 72.3
      years old and the frequency of hypertension was 47.6%. There was no ventricular
      fibrillation (VF) when the patients with AD collapsed. A loss of consciousness
      was the most common complaint. The outcome of the subjects was poor; however,
      three patients with SA achieved social rehabilitation. Two out of the three had
      cardiac tamponade and underwent open heart massage. CONCLUSION: The current study
      revealed that mortality of cardiac arrest caused by the AD remains very high,
      even when return of spontaneous circulation was obtained. VF was rare when the
      patients with AD collapsed. While some cases with CPA of SA may achieve a
      favorable outcome following immediate appropriate treatment.

PMID- 23960371
TI  - Where do I go? A trauma victim's plea in an informal trauma system.
AB  - BACKGROUND: The three pillars of a good trauma system are the prehospital care,
      definitive care, and rehabilitative services. The prehospital care is a critical
      component of the efforts to lower trauma mortality. OBJECTIVE: To study the
      prehospital profile of patients who died due to trauma, compute the time taken to
      reach our facility, find the cause of delay, and make feasible recommendations.
      MATERIALS AND METHODS: A hospital-based study was performed at a trauma center in
      Puducherry from June 2009 to August 2010. Puducherry is a union territory of
      India in the geographical terrain of the state of Tamil Nadu. A total of
      241deaths due to trauma were included. Apart from the demographic and injury
      characteristics, a detailed prehospital log was constructed regarding the time of
      incident, the referral patterns, care given in the prehospital phase, the
      distance travelled, and the total time taken to reach our center. RESULTS: The
      majority (59%) of patients were referred, with stopovers at two consecutive
      referral centers (30%), needing at least two vehicles to transport to definitive
      care (70%), clocking unnecessary distances (67%), and delayed due to non
      therapeutic intervention (87%). The majority of deaths (66%) were due to head
      injury. Only 2.96% of referred cases reached us within the first hour. Few of the
      patients coming directly to us had vehicle change due to local availability and
      lack of knowledge of predestined definitive care facility. Overall, 94.6% of
      direct cases arrived within 4 h whereas 93.3% of referred cases required up to 7
      h to arrive at definitive care. CONCLUSIONS: Seriously injured patients lose
      valuable prehospital time because there is no direction regarding destination and
      interfacility transfer, a lack of seamless transport, and no concept of initial
      trauma care. The lack of direction is compounded in geographical areas that are
      situated at the border of political jurisdictions.

PMID- 23960372
TI  - Blood levels of histone-complexed DNA fragments are associated with coagulopathy,
      inflammation and endothelial damage early after trauma.
AB  - BACKGROUND: Tissue injury increases blood levels of extracellular histones and
      nucleic acids, and these may influence hemostasis, promote inflammation and
      damage the endothelium. Trauma-induced coagulopathy (TIC) may result from an
      endogenous response to the injury that involves the neurohumoral, inflammatory
      and hemostatic systems. AIMS: To study the contribution of extracellular nucleic
      constituents to TIC, inflammation and endothelial damage. SETTING AND DESIGN:
      Prospective observational study. MATERIALS AND METHODS: We investigated histone
      complexed DNA fragments (hcDNA) along with biomarkers of coagulopathy,
      inflammation and endothelial damage in plasma from 80 trauma patients admitted
      directly to the Trauma Centre from the scene of the accident. Blood was sampled a
      median of 68 min (IQR 48-88) post injury. Trauma patients with hcDNA levels
      >median or <=median were compared. RESULTS: Trauma patients with high plasma
      hcDNA had higher Injury Severity Score (ISS) and level of sympathoadrenal
      activation (higher adrenaline and noradrenaline) and a higher proportion of
      prolonged activated partial thromboplastin time (APTT) and higher D-dimer, tissue
      type plasminogen activator (tPA), Annexin V and soluble CD40 ligand (sCD40L)
      concurrent with lower plasminogen activator inhibitor (PAI)-1) and prothrombin
      fragment (PF) 1 + 2 (all P < 0.05), all indicative of impaired thrombin
      generation, hyperfibrinolysis and platelet activation. Furthermore, patients with
      high hcDNA had enhanced inflammation and endothelial damage evidenced by higher
      plasma levels of terminal complement complex (sC5b-9), IL-6, syndecan-1,
      thrombomodulin and tissue factor pathway inhibitor (all P < 0.05). CONCLUSIONS:
      Excessive release of extracellular histones and nucleic acids seems to contribute
      to the hypocoagulability, inflammation and endothelial damage observed early
      after trauma.

PMID- 23960373
TI  - Evaluation of the relationship between pelvic fracture and abdominal compartment
      syndrome in traumatic patients.
AB  - INTRODUCTION: An increase in abdominal pressure can lead to so-called intra
      abdominal compartment syndrome (ACS). Multiple factors such as an increase in
      retroperitoneal volume due to pancreatitis, bleeding and edema as a result of
      pelvic fracture can lead to compartment syndrome. Prevention is better than cure
      in compartment syndrome. By measuring the intra-abdominal pressure (IAP) through
      the bladder, a quick and accurate assessment of abdominal pressure is achieved.
      Therefore, this study aimed to evaluate the relationship between pelvic fracture
      and ACS in traumatic patients. MATERIALS AND METHODS: This research was a
      descriptive-analytical study conducted on 100 patients referring to the Shiraz
      Nemazee Hospital in 2010. IAP was monitored every 4 h in patients suspected to be
      at high risk for ACS, e.g., those undergoing severe abdominal trauma and pelvic
      fracture. The IAP was measured via the urinary bladder using the procedure
      described by Kron et al. Data collected were analyzed using SPSS software.
      RESULTS: The findings showed that ACS occurred in 28 of 100 patients. With regard
      to the associated injuries with abdominal trauma, 19% of all patients and 46/42%
      of the patients with ACS had pelvic fracture. Chi-square test revealed a
      significant relationship between pelvic fracture and incidence rate of ACS (P <
      0.001). CONCLUSIONS: According to the collected data, pelvic fracture due to a
      trauma can be one of the important causes of an increase in IAP and ACS. In this
      lethal condition, prevention is better than cure. Therefore, serial measurement
      of IAP through the bladder in high-risk patients (those with pelvic fracture by
      trauma) is recommended to the nurses to diagnose this condition and to decrease
      the incidence of mortality.

PMID- 23960374
TI  - Coagulopathy as prognostic marker in acute traumatic brain injury.
AB  - CONTEXT: Coagulopathy frequently occurs following traumatic brain injury (TBI)
      and usually occurs 6-72 hour post-trauma. The incidence and the probable risk
      factors for development of coagulopathy and poor outcome following TBI are
      largely unknown and vary considerably. AIMS: To assess the incidence and probable
      risk factors for development of coagulopathy and to identify the risk factors for
      poor outcome in terms of median survival time following TBI. MATERIALS AND
      METHODS: In this prospective study over two years, patients of isolated moderate
      and severe traumatic brain injury (GCS<=12) admitted to trauma center had
      coagulation profile (PT, APTT, thrombin time, fibrinogen and D-dimer), arterial
      lactate and ABG analysis done on day of admission and on day three. Coagulopathy
      was defined as prothrombin time (PT) or/and activated partial thromboplastin time
      (APTT) more than 1.5 times the normal control. Incidence of in-hospital mortality
      was assessed in all cases. STATISTICAL ANALYSIS: A stepwise logistic regression
      analysis was performed to identify risk factors for coagulopathy and mortality in
      these patients. RESULTS: A total of 208 patients were enrolled in the study. The
      mean age was 32 +/- 12 years and mean GCS was 7.1 +/- 2.8. Coagulopathy was
      present in 46% (n = 96) of patients. Risk factors for development of coagulopathy
      were found out to be severity of head injury (OR: 2.81), elevated D-dimer (OR:
      3.43), low hemoglobin (OR: 3.13), and effaced cisterns in the CT scan (OR: 2.72).
      Presence of coagulopathy (OR: 2.97) and severity of head injury (OR: 5.70)
      strongly predicted poor outcome, and were associated with a decreased median
      survival time. CONCLUSIONS: There is a high incidence of coagulopathy following
      TBI. The presence of coagulopathy as well as of severity of TBI are strong
      predictors of in-hospital mortality in these patients.

PMID- 23960375
TI  - Splenectomy in a Nigerian Teaching Hospital: A comparison of sonographic
      correlation with intra-operative findings in trauma.
AB  - BACKGROUND: Missed or inappropriately-treated splenic injury is a significant
      cause of preventable trauma-related death. Physical examination and abdominal
      ultrasonography are essential tools for early diagnosis of splenic injury.
      However, some injuries may not be accurately diagnosed by ultrasonography at
      initial evaluation. AIM: The aim of this study was to audit indications for
      splenectomy at the University College Hospital, Ibadan and to compare the intra
      operative findings in trauma-related cases with the sonographic findings.
      MATERIALS AND METHODS: We retrospectively reviewed all adult (12 years and older)
      patients' records who had splenectomy between July 2003 and June 2010. The data
      extracted included patient demographics and indications for splenectomy. In
      trauma cases, the mode of injury and vital signs at presentation, sonographic
      findings, and operation findings were recorded. The intervals between injury and
      sonography and duration to surgery were also noted respectively. RESULTS: Eighty
      four patients were reviewed in the 7-year review period. The male to female ratio
      was approximately 2:1. The ages ranged from 14 to 76 years with a peak incidence
      in the third decade. Elective indications for splenectomy were 14 (16.6%), while
      70 (83.3%) were emergency cases. Forty-four of the trauma-related patients had
      pre-operative abdominal ultrasound, of which 31 (70%) was reported as
      sonographically normal prior to surgery, while the rest of the trauma-related
      cases were considered too ill for ultrasonography. CONCLUSION: Potentially
      significant injuries may be missed with screening sonography. For this reason, a
      physician must maintain a high index of suspicion and consider the patient's
      clinical status or an alternative imaging modality in excluding a diagnosis of
      splenic injury.

PMID- 23960376
TI  - Effect of cocaine use on outcomes in traumatic brain injury.
AB  - CONTEXT: Animal and molecular studies have shown that cocaine exerts a
      neuroprotective effect against cerebral ischemia. AIMS: To determine if the
      presence of cocaine metabolites on admission following traumatic brain injury
      (TBI) is associated with better outcomes. SETTINGS AND DESIGN: Level-1 trauma
      center, retrospective cohort. MATERIALS AND METHODS: After obtaining
      Institutional Review Board (IRB) approval, the trauma registry was searched from
      2006 to 2009 for all patients aged 15-55 years with blunt head trauma and non
      head AIS <3. Exclusion criteria were pre-existing brain pathology and death
      within 30 min of admission. The primary outcome was in-hospital mortality;
      secondary outcomes were hospital length of stay (LOS), and Glasgow Outcome Score
      (GOS). STATISTICAL ANALYSIS: Logistic regression was used to determine the
      independent effect of cocaine on mortality. Hospital LOS was compared with
      multiple linear regression. RESULTS: A total of 741 patients met criteria and had
      drug screens. The screened versus unscreened groups were similar. Cocaine
      positive patients were predominantly African-American (46% vs. 21%, P < 0.0001),
      older (40 years vs. 30 years, P < 0.0001), and had ethanol present more often
      (50.7% vs. 37.8%, P = 0.01). There were no differences in mortality (cocaine
      positive 1.4% vs. cocaine-negative 2.7%, P = 0.6) on both univariate and
      multivariate analysis. CONCLUSIONS: Positive cocaine screening was not associated
      with mortality in TBI. An effect may not have been detected because of the low
      mortality rate. LOS is affected by many factors unrelated to the injury and may
      not be a good surrogate for recovery. Similarly, GOS may be too coarse a measure
      to identify a benefit.

PMID- 23960377
TI  - Bedside ultrasonography by emergency physicians for anterior talofibular ligament
      injury.
AB  - OBJECTIVE: Our objective was to study the accuracy of emergency physician (EP)
      performed bedside ultrasonography (BUS) in patients with suspected anterior
      talofibular ligament (ATFL) injury. MATERIALS AND METHODS: After a 6-h training
      program, from January to December 2011, an EP used BUS to prospectively evaluate
      patients presenting to the emergency department (ED) with suspected ATFL injury.
      Then, patients underwent ankle X-ray and Magnetic Resonance (MR) imaging. Outcome
      was determined by official radiology reports of the MR imaging. BUS and MR
      imaging results were compared using Chi-square testing. RESULTS: Of the 65
      enrolled patients, 30 patients were BUS positive. Of these, MR imaging results
      agreed with the BUS findings in 30 patients. In 35 cases, BUS was negative, and
      33 of these were corroborated by MR imaging. The sensitivity, specificity,
      positive predictive value, negative predictive value, and negative likelihood
      ratio for BUS were 93.8%, 100%, 100%, 94.3%, and 0.06%, respectively. The
      diagnostic accuracy of BUS was not statistically different from MR imaging (K =
      0.938, P = 0.001). CONCLUSION: BUS for the diagnosis of ATFL injury is another
      application of BUS in the ED. EPs can diagnose ATFL injury using BUS with a high
      degree of accuracy.

PMID- 23960378
TI  - Demographic, epidemiologic and clinical profile of snake bite cases, presented to
      Emergency Medicine department, Ahmedabad, Gujarat.
AB  - AIM: Snake bite is a common medical emergency faced mainly by the rural
      populations in tropical and subtropical countries with heavy rainfall and humid
      climate. Although India is a single largest contributor of snake bite cases,
      reporting is very poor. There is hardly any publication of the same from Gujarat
      state that is developing at a good pace. Hence, we aimed to study the snake bite
      cases with particular attention to demography, epidemiology, and clinical
      profile. SETTINGS AND DESIGN: The present descriptive, observational study was
      carried out at the Emergency Medicine Department of a tertiary care center in
      Ahmedabad, Gujarat. This department is one if the firsts to get recognized by the
      Medical Council of India. MATERIALS AND METHODS: This is a cross-sectional single
      center study. Cases were entered into the prescribed form, and detailed
      information regarding demographic, epidemiologic, and clinical parameters was
      entered. STATISTICAL METHOD: Data were analyzed using Epi2000. Means and
      frequencies for each variable were calculated. RESULTS: Majority (67.4%) of the
      snake bite victims were in the age group between 15 and 45 years. Majority were
      male victims (74.2%). 71% victims of snake bite lived in rural areas. Farmers and
      laborers were the main victims. 61.2% incidents took place at night time or early
      morning (before 6 a.m.). 64% patients had bite mark on the lower limb. 40%
      victims had seen the snake. Eight patients had snake bite, but were asymptomatic.
      52% had neuroparalytic manifestation, 34% were asymptomatic, and 9.6% had
      hemorrhagic manifestation. 14% cases received treatment within 1 h of the bite
      and 64.84% within 1-6 h after the bite. First aid given was in the form of
      application of tourniquet (16.2%), local application of lime, chillies, herbal
      medicine, etc., (1%). 2.20% cases were sensitive to anti-snake venom. Only three
      patients died. CONCLUSION: In this region (Gujarat), neuroparalytic manifestation
      of snake bite is more prevalent. Cobra and krait are the commonest types of
      poisonous snakes. The time of seeking treatment has reduced because of awareness
      about snake bite treatment and better transport and ambulance facility. Mortality
      is very less in well-equipped hospitals due to early initiation of treatment with
      anti-snake venom.

PMID- 23960379
TI  - The role of allopurinol's timing in the ischemia reperfusion injury of small
      intestine.
AB  - INTRODUCTION: Allopurinol acts protectively in the ischemia reperfusion injury of
      the small intestine. The aim of this experimental study is to define the ideal
      time of administration of allopurinol, in experimental models of
      ischemia/reperfusion. MATERIALS AND METHODS: We used 46 rabbits that were divided
      into four groups. Group A was the control. In Group B allopurinol was
      administered 10 min before ischemia and in Group C 2 min before reperfusion. In
      Group D, allopurinol was administered before ischemia and before reperfusion in
      half doses. Blood samples were collected at three different moments: (t1) prior
      to ischemia, (t2) prior to reperfusion, and (t3) after the end of the
      reperfusion, in order to determine superoxide dismutase (SOD) and neopterin
      values. Specimens of the intestine were obtained for histological analysis and
      determination of malondialdehyde (MDA). RESULTS: In Group A, mucosal lesions were
      more extensive compared to those of the other three groups. Similarly, MDA, SOD
      and neopterin values were significantly higher. On the contrary, Group D showed
      the mildest mucosal lesions, as well as the lowest MDA, SOD and neopterin values.
      Finally, the lesions and the above mentioned values were bigger in Group C than
      in Group D. CONCLUSIONS: The administration of allopurinol attenuates the
      production and damage effect of free oxygen radicals during ischemia reperfusion
      of the small intestine, thus protecting the intestinal mucosa. Its maximum
      beneficial action is achieved when administered both before ischemia and before
      reperfusion of the small intestine.

PMID- 23960380
TI  - Reduction of pediatric emergency hospital admissions by a change in pediatric
      emergency department policy.
AB  - BACKGROUND: Reduction in admissions is an important aim of emergency department
      working policy to overcome the problems of a shortage of inpatient beds, rising
      costs and exhausted resources. A new policy was instituted in the pediatric
      emergency department (PED) of a hospital in Kuwait with the following components:
      (1) assigning senior doctor staff (2) implementation of new disease management
      guidelines; and (3) maximizing the use of the pediatric emergency department
      observation unit. OBJECTIVE: to evaluate the effect of change in our policy on
      the admission rate. MATERIALS AND METHODS: The effects of this policy on
      reduction of admission rates for total pediatric admissions and for some selected
      common pediatric conditions were prospectively studied over a period of 3 years
      from institution of the policy and compared with the 3-year period before the
      policy was instituted. RESULTS: There was a significant reduction in admission
      rates after institution of the new policy. The proportion of hospital admissions
      to PED observation unit cases was significantly reduced as a whole from 64.9% +/-
      5.1% to 33.2 +/- 0.6% and also for the common pediatric problems studied.
      CONCLUSION: A multidisciplinary pediatric emergency department policy, using as
      much available evidence as possible, was successful in significantly reducing
      pediatric hospital admissions.

PMID- 23960381
TI  - Images in medicine: Diagnosis and pre-surgical triage of transanal rectal injury
      using multidetector CT with water-soluble contrast enema.
AB  - Transanal rectal injuries caused by foreign body insertion, sexual abuse, or
      iatrogenic procedures represent a very uncommon surgical emergency. Morbidity may
      be further increased by patient's embarrassment and delayed presentation. Since
      management decisions largely depend on anatomic and severity assessment,
      multidetector Computed tomography with rectally administered water-soluble
      iodinated contrast medium is highly valuable to accurately depict traumatic
      rectal injuries, and to distinguish between intraperitoneal vs extraperitoneal
      injuries that require different surgical approaches. 

PMID- 23960382
TI  - Academic College of Emergency Experts in India's INDO-US Joint Working Group
      (JWG) White Paper on the Integrated Emergency Communication Response Service in
      India: Much more than just a number!
AB  - The proposal for an integrated national emergency number for India is garnering a
      lot of enthusiasm and stimulating debate. This ambitious project has a two-part
      paradigm shift to set in; the first being the integration into a single number
      and the infrastructure required for setting up and operating this number such
      that a call can be received and identified. The second is the submerged part of
      the iceberg: That of the ability to respond to a call and deliver the appropriate
      emergency service. The first part is more technical and has potential precedents
      like the 911 phone hotline, for example, to emulate. The main premise of this
      paper is that the second part is a rather subjective exercise largely determined
      by the realities of existing public infrastructure in a specific geographical
      area with respect to emergency services management, especially medical care.
      Consequently, we highlight the key areas of both precall preparedness and
      postcall execution that need to be reviewed prior to going live with an
      integrated number on a national scale. 

PMID- 23960383
TI  - Small bowel obstruction in percutaneous fixation of traumatic pelvic fractures.
AB  - The use of external fixation for the initial treatment of unstable, complex
      pelvic injuries with hemodynamic instability remains an effective treatment for
      multiply injured patients. Bowel entrapment within a pelvic fracture is a rarely
      reported, potentially fatal complication. Here, we report a polytrauma patient
      with pelvic fractures who developed an intestinal obstruction after an external
      fixation. At an explorative laparotomy, we found an ileum segment trapped in the
      sacral fracture. Reported cases of bowel entrapment in pelvic fractures,
      especially in sacral fractures, are exceedingly rare. The diagnosis is often
      delayed due to difficulty distinguishing entrapment from the more common adynamic
      ileus. In conclusion, clinicians and radiologists should be aware of this
      potentially lethal complication of pelvic fractures treatment. To exclude bowel
      entrapment, patients with persistent ileus or sepsis should undergo early
      investigations. 

PMID- 23960385
TI  - Contre-coup injury in chest: Report of two cases.

PMID- 23960384
TI  - Hypothermic overdose, not all bad?
AB  - A 51-year-old woman was brought into the Emergency Department (ED) following an
      intentional overdose of alcohol and her medication. Along with two bottles of
      wine it was estimated that she had taken 5800 mg of Quetiapine and 240 mg of
      Citalopram along with the wine. The ambient temperature in her flat was thought
      to be 10 degrees C. On arrival to the ED her GCS was 8. She had agonal
      respirations with a pulse of 56/min, hypotensive 55/35 mmHg and a temperature 24
      degrees C. The patient was intubated and was given sodium bicarbonate, magnesium
      sulphate, calcium gluconate and an adrenaline infusion. She received active and
      passive rewarming measures. She had significant ECG findings related to her
      hypothermia and polypharmacy overdose which seemed to have been cumulative. The
      patient recovered and the only neurological deficit was numbness in her left leg
      which was thought to be related to prolonged immobility. Hypothermia may have
      contributed to her good outcome as hypothermia has been shown to improve both
      cardiac and neurological outcome. 

PMID- 23960386
TI  - A unique case of non- traumatic asymmetric shoulder dislocation with four-part
      fractures of proximal humeri following seizures.

PMID- 23960387
TI  - The hair: melanocyte nexus.

PMID- 23960388
TI  - Desmogleins: hair perspective.
AB  - Desmogleins (Dsgs) are calcium-dependent, transmembrane glycoproteins belonging
      to the desmosomal cadherin superfamily, which play significant roles in selective
      calcium ions (Ca(2+)) dependent adhesion interactions between cell surfaces. Four
      subtypes of Dsg have been identified. Recent observations show the distribution
      of Dsgs can correlate with specific types of keratinization, anchorage of the
      hair, and hypotrichosis. 

PMID- 23960389
TI  - A randomized evaluator blinded study of effect of microneedling in androgenetic
      alopecia: a pilot study.
AB  - INTRODUCTION: Dermal papilla (DP) is the site of expression of various hair
      growth related genes. Various researches have demonstrated the underlying
      importance of Wnt proteins and wound growth factors in stimulating DP associated
      stem cells. Microneedling works by stimulation of stem cells and inducing
      activation of growth factors. MATERIALS AND METHODS: Hundred cases of mild to
      moderate (III vertex or IV) androgenetic alopecia (AGA) were recruited into 2
      groups. After randomization one group was offered weekly microneedling treatment
      with twice daily 5% minoxidil lotion (Microneedling group); other group was given
      only 5% minoxidil lotion. After baseline global photographs, the scalp were
      shaved off to ensure equal length of hair shaft in all. Hair count was done in 1
      cm(2) targeted fixed area (marked with tattoo) at baseline and at end of therapy
      (week 12). The 3 primary efficacy parameters assessed were: Change from baseline
      hair count at 12 weeks, patient assessment of hair growth at 12 weeks, and
      investigator assessment of hair growth at 12 weeks. A blinded investigators
      evaluated global photographic response. The response was assessed by 7- point
      scale. RESULTS: (1) Hair counts - The mean change in hair count at week 12 was
      significantly greater for the Microneedling group compared to the Minoxidil group
      (91.4 vs 22.2 respectively). (2) Investigator evaluation - Forty patients in
      Microneedling group had +2 to +3 response on 7-point visual analogue scale, while
      none showed the same response in the Minoxidil group. (3) Patient evaluation - In
      the Microneedling group, 41 (82%) patients reported more than 50% improvement
      versus only 2 (4.5%) patients in the Minoxidil group. Unsatisfied patients to
      conventional therapy for AGA got good response with Microneedling treatment.
      CONCLUSION: Dermaroller along with Minoxidil treated group was statistically
      superior to Minoxidil treated group in promoting hair growth in men with AGA for
      all 3 primary efficacy measures of hair growth. Microneedling is a safe and a
      promising tool in hair stimulation and also is useful to treat hair loss
      refractory to Minoxidil therapy.

PMID- 23960390
TI  - Trichomycosis (trichobacteriosis): clinical and microbiological experience with
      56 cases.
AB  - BACKGROUND: Trichomycosis is asymptomatic bacterial infection of the axillary
      hairs caused by Corynebacterium sp. OBJECTIVE: to bring a series of cases of
      trichomycosis, its clinical and microbiological experience. MATERIALS AND
      METHODS: This report consists in a linear and observational retrospective study
      of 15 years of cases of trichomycosis confirmed clinically and microbiologically.
      RESULTS: Fifty six confirmed cases of trichomycosis were included in this report.
      The majority were men 53/56 (94.6%), mean age was 32.5 years. The most commonly
      affected area was the axilla (92%), trichomycosis flava was the principal variant
      55/56 (98.2%) and signs and symptoms associated were hyperhidrosis (87.5%),
      hairs' texture change (57.1%) and odor (35.7%). Bacterial concretions were
      observed in all cases, and the predominant causative agent in 89.3% of all cases
      was Corynebacterium sp. Thirty patients were included in therapeutic portion of
      the study, and 28 (93.3%) of them experienced a clinical and microbiological
      cure. CONCLUSION: Trichomycosis is asymptomatic, superficial infection, which
      primarily affects axillary hairs.

PMID- 23960392
TI  - Finasteride 5 mg/day Treatment of Patterned Hair Loss in Normo-androgenetic
      Postmenopausal Women.
AB  - BACKGROUND: There is no consensus on the standard treatment options for female
      pattern androgenetic alopecia (AGA). Efficacy of finasteride in women is
      controversial. The purpose of this study was to evaluate the clinical efficacy
      and safety of 5 mg/day oral finasteride in normoandrogenic postmenopausal woman.
      MATERIALS AND METHODS: A total of 40 normoandrogenic postmenopausal women with
      AGA was enrolled in this study. They were treated with oral finasteride 5 mg/day
      for 18 months. Efficacy was evaluated by patient's satisfaction and global
      photograph assessment. All the 40 patients completed 18 months of finasteride
      treatment schedule. RESULTS: After 6 months, 22 patients referred significant
      improvement, 12 moderate improvement, and 6 no improvement. Regarding to global
      photo assessment, 8 patients showed no improvement, 16 showed moderate
      improvement and 16 showed significant improvements at the 6(th) month. A slight
      improvement was observed over time from 6 to 12 and 18 months observation.
      Maintained libido reduction was referred by four patients and liver enzymes
      increase was observed in one patient. Older patients were more prone to worse
      response. DISCUSSION: Finasteride 5 mg/day is effective and safe for the
      treatment of female AGA in postmenopausal women in the absence of clinical or
      laboratory signs of hyper-androgenism.

PMID- 23960391
TI  - Epidemiological and investigative study of premature graying of hair in higher
      secondary and pre-university school children.
AB  - BACKGROUND: Hair pigmentation is one of the most conspicuous phenotypes in humans
      ranging from black, brown, and blonde to red. Premature graying of hair occurs
      more commonly without any underlying pathology but is said to be inherited in
      autosomal dominant pattern. Premature graying has been shown to be associated
      with a few of the autoimmune disorders. A role for environmental factors and
      nutritional deficiencies has also been postulated. However, to date the exact
      etiology of premature graying has not been established. AIM: The objective of our
      study was to conduct an epidemiological and investigative study of premature
      graying of hair in higher secondary and pre-university school children of the
      semi-urban area. MATERIALS AND METHODS: A total of 35 cases and controls were
      investigated for various parameter such as Hemoglobin, total iron binding
      capacity, serum ferritin (S. Ferritin), serum calcium (S. Ca), serum iron (S.
      Iron), vitamin B12, and vitamin D3 after taking informed consent. Epidemiological
      and investigations correlation was established using the Chi-square and Mann
      Whitney test and P < 0.05 values were considered significant. RESULT: Among the
      various laboratory parameters S. Ca, S. Ferritin and vitamin D3 were low in
      patients with premature graying of hair. There was significant high number of
      vitamin D3 deficient and insufficient among the cases compared to the controls.
      CONCLUSION: According to our study S. Ca, S. Ferritin, vitamin D3 may play a role
      in premature graying of hair in our society.

PMID- 23960393
TI  - Chemical hair relaxers have adverse effects a myth or reality.
AB  - CONTEXT: Hair plays an important role in one's personality and builds confidence.
      Now-a-days, chemical hair relaxers are used very commonly in the society. We
      document the adverse effects reported by the sample that have used any one of the
      professional chemical hair relaxers. AIM: To study the adverse effects reported
      by the sample who underwent repeated chemical hair relaxing. SETTINGS AND DESIGN:
      Cross-sectional questionnaire based study done on a sample taken from a medical
      college and hospital campus in Mangalore. MATERIALS AND METHODS: The sample was
      restricted to females and to those who underwent it more than once. A
      questionnaire was given to a sample of 90, which matched our criteria.
      STATISTICAL ANALYSIS: SPSS software 17. RESULTS: Adverse effects reported by the
      sample after undergoing the procedure were found to be a high 95.56%, out of
      which the following are the common adverse effects reported; frizzy hair in 67%,
      dandruff in 61%, hair loss in 47%, thinning and weakening of hair in 40%, greying
      of hair 22%, and split ends in only 17%. CONCLUSIONS: Very few studies have been
      conducted on the adverse effects of hair straightening products in India. From
      our study, it can be stated that most of the samples had adverse effects, which
      was as high as 95.56%. Hence from the details elicited from this study, we can
      conclude that, usage of chemical hair relaxers does cause adverse effects and is
      "not a myth." Thus, it is necessary to make available a less harmful chemical
      hair relaxer to the society.

PMID- 23960394
TI  - Keratosis follicularis spinulosa decalvans: a rare cause of scarring alopecia in
      two young Indian girls.
AB  - Keratosis follicularis spinulosa decalvans (KFSD) is an X-linked xenodermatosis
      characterized by scarring alopecia and follicular hyperkeratosis. This condition
      mainly affects males with females being carriers and will have milder symptoms.
      We present two sisters with severe form of KFSD, progressing to scarring
      alopecia. 

PMID- 23960395
TI  - Bullous pilomatricoma: a rare variant resembling bouncy ball.
AB  - Pilomatricoma (pilomatrixoma) or calcifying epithelioma of Malherbe, is a tumor
      with differentiation toward hair cells, particularly hair cortex cells. It
      frequently presents as a firm, deep-seated nodule that is covered by normal skin.
      Bullous pilomatricoma is an unusual clinical variant. Reports on bullous variant
      of pilomatricoma is sparse, and only 17 cases have been reported world-wide until
      date out of which only two cases are reported from India. We present a report of
      a 17-year-old female with a solitary reddish semi-transparent blister over her
      right upper arm since 3 months resembling a bouncy ball. Histopathology revealed
      tumor nests of basophilic cells and eosinophilic shadow cells, which are
      consistent with pilomatricoma. 

PMID- 23960396
TI  - Trichothiodystrophy in a child with occult learning disorder.
AB  - Trichothiodystrophy (TTD) is an autosomal recessive condition characterized by
      brittle and sparse sulfur deficient hair. The disorder is due to a known genetic
      mutation in DNA nucleotide excision repair (NER) in up to 83% of cases. We
      describe a 13-month-old girl presenting with hair fragility and hair loss since
      age 3 months, and discuss the overlap between TTD and other NER diseases. This
      case report highlights the importance of early diagnosis of occult learning
      disorder in young children with TTD and the need for early assessment and
      involvement of multidisciplinary team to target the child's educational needs. 

PMID- 23960397
TI  - Trichotillomania in a case of vascular dementia.
AB  - Trichotillomania is a complex psychiatric disorder and occurs along with a large
      number of comorbidity. We report a case of trichotillomania associated with
      vascular dementia. Trichotillomania in our case did not resolve using mirtazapine
      or conventional medications. Trichotillomania in dementia seems to have a
      neurobiological origin that needs to be elucidated. 

PMID- 23960398
TI  - Zinc deficiency associated with hypothyroidism: an overlooked cause of severe
      alopecia.
AB  - Hypothyroidism is a common and well recognized cause of diffuse hair loss. Zinc
      and other trace elements such as copper and selenium are required for the
      synthesis of thyroid hormones, and deficiency of these can result in
      hypothyroidism. Conversely, thyroid hormones are essential for the absorption of
      zinc, and hence hypothyroidism can result in acquired zinc deficiency. The hair
      loss attributed to hypothyroidism may not improve with thyroxine unless zinc
      supplements are added, as demonstrated in our case. 

PMID- 23960399
TI  - Allergic contact dermatitis to superglue.
AB  - Wigs are commonly used to cover baldness. A 28 year old male presented with itchy
      oozy eythematous lesions on the forehead where the wig was afixed to the scalp.
      Patch testing with indian standard seies and dental series revealed positivity to
      2-hydroxy ethyl meta acrylate present in superglue. We report this case for its
      clinical rarity. 

PMID- 23960400
TI  - Short anagen hair syndrome.
AB  - Short anagen syndrome (SAS) is a condition in which hair does not grow long. It
      usually perceived by parents in children around 2-4 years of age. It is a benign
      disease of the hair cycle. The condition is relevant from the standpoint of
      differential diagnosis with loose anagen syndrome. We report a case of SAS in a
      Hispanic 3-year-old girl. 

PMID- 23960401
TI  - Alopecia areata treated with phenolisation and intravenous dexamethasone pulses.
AB  - Phenol is an aromatic hydrocarbon derived from coal tar or manufactured from
      monochlorobenzene. Alopecia areata is a common non scarring autoimmune condition
      characterised by patchy loss of hair without atrophy. Various treatment
      modalities have been proposed and used for the treatment of alopecia areata,
      which is indeed a difficult condition to treat. Variable results have been
      documented using intralesional corticosteroid injections, topical minoxidil,
      topical anthralin ointment, topical contact sensitizers like diphencyprone,
      dinitrochlorobenzene or squaric acid dibutyl ester, and oral mini pulse with
      betamethasone. The use of 88% phenol for the treatment of alopecia areata has
      been documented in literature, but it has failed to secure a place in the
      priority list. Herein we have reported a case of a young girl who was treated
      with short-time aggressive therapy using 88% phenol and dexamethasone pulse
      therapy and who responded well to the treatment with no recurrence in the last 6
      months of follow-up. 

PMID- 23960403
TI  - Monilethrix with variable expressivity.
AB  - Monilethrix is a rare autosomal dominant hair shaft disorder with variable
      expressivity. It usually presents with short broken scalp hairs and follicular
      hyperkeratosis. Light microscopy of hair reveals a beaded appearance. Here, we
      report the case of a 32-year-old male who presented with sparse hair and
      follicular keratotic papules in the absence of any family history. 

PMID- 23960402
TI  - Colocalization of vitiligo and alopecia areata: coincidence or consequence?
AB  - Both alopecia areata (AA) and vitiligo are autoimmune diseases, and their
      coexistence in the same patient is not uncommon, as vitiligo has been reported to
      occur in 4.1% of patients of AA. We present a case of a 15-year-old male child
      who had vitiligo and later developed AA over the existing lesions of vitiligo
      over face and scalp and have attempted to elucidate the current understanding of
      mechanisms of coexistence of these two diseases. Our case lends support to the
      hypothesis that AA and vitiligo share a common pathogenic pathway including
      autoimmune response against some common antigens like those derived from the bulb
      melanocytes. Stimulation of proinflammatory T-helper(Th)-1 cell mediated
      immunological response or inactivation of a suppressor T-cell mediated response
      could be the common underlying phenomenon. However, the striking rarity of
      colocalization of these two diseases has led to the recent debate over current
      understanding of their pathogenesis, and whether this association is merely a
      coincidence. As both AA and vitiligo are frequent and chronic dermatological
      disorders, it is of utmost importance to gain more understanding into their
      pathogenic mechanisms so that more definitive treatment modalities may be devised
      and the quality of life of these patients can be improved. 

PMID- 23960404
TI  - A childhood case of trichotillomania associated with body dysmorphic disorder and
      stigmatization due to outstanding red hair.

PMID- 23960405
TI  - A Descriptive Study of Alopecia Patterns and their Relation to Thyroid
      Dysfunction.

PMID- 23960406
TI  - A model road map to the practice of forensic odontology.

PMID- 23960407
TI  - Utility of cheiloscopy, rugoscopy, and dactyloscopy for human identification in a
      defined cohort.
AB  - BACKGROUND: Identification is of paramount importance in any forensic
      investigation. Positive identification of living or deceased using distinctive
      traits is a cornerstone of forensic science. The uniqueness of these patterns and
      subtle distinction between traits has offered worthy supplemental tools in
      establishing the true nature of facts. AIM: The first aim of our study was to
      determine the most common pattern of lip prints, palatal rugae, and finger prints
      in the study subjects. Secondly, to determine if any specific pattern of lip
      print, palatal rugae, or the finger print concurs in individuals, and thereby
      establish a database of these prototypes for human identification from a defined
      cohort. MATERIALS AND METHODS: The sample size comprised 100 female students of a
      dental college staying together in the hostel. Lip prints were recorded on a
      white bond sheet using lipstick, palatal rugae on dental casts, and finger prints
      using printer's blue ink. RESULTS: Our observation suggested that the reticular
      pattern of lip print, the wavy pattern of palatal rugae, and the loop pattern of
      finger prints were the predominant patterns. Correlation of the three parameters
      did not reveal significant differences. CONCLUSIONS: This approach of human
      identification utilizing conventional techniques and relevant parameters is
      pertinent in defined groups. However, larger representative sample with robust
      analytical tools may provide a necessary blueprint of human identification.

PMID- 23960408
TI  - Are teeth evidence in acid environment.
AB  - AIM: Teeth are the most durable structures that resist destruction more than
      skeletal tissue Commercially available acids can be used to destroy the body or a
      part, to mask human identification. The present study examines the effect of
      caustic acids on human dentition. MATERIALS AND METHODS: Ten upper anterior teeth
      each were immersed in 37% hydrochloric acid (conc. HCl), 65% nitric acid (conc.
      HNO3) and 96% sulfuric acid (conc. H2SO4). Teeth were retrieved, washed in
      distilled water, dried, photographed and radiographed at intervals of 15 min, 30
      min, 1 hr, 3 hr, 5 hr and 8 hr. RESULTS: Teeth placed in conc. HCl and conc. HNO3
      dissolved completely after 8 hours, while that placed in conc. H2SO4 retained its
      morphology and radiographic dimension even after 8 hours. CONCLUSION: Hence teeth
      can serve as a tool in identification (age estimation and sex determination) of
      the victim when in contact with conc. H2SO4.

PMID- 23960409
TI  - Comparison of lip prints in two different populations of India: Reflections based
      on a preliminary examination.
AB  - BACKGROUND: Dental records, fingerprint, and DNA comparisons are probably the
      most common techniques used for a person's identification, allowing fast and
      secure identification processes. However, sometimes it is necessary to apply
      different and less known techniques such as lip prints. The potential of lip
      prints to determine sex has been well exhibited and documented. However, very few
      studies have been conducted using lip prints for population identification.
      OBJECTIVE: To determine the predominant lip print patterns in males and females
      in relation to Kerala and Manipuri population and also to compare the lip print
      patterns between these populations. MATERIALS AND METHODS: The sample comprised
      of 60 subjects, which included 30 each from Kerala and Manipuri. Lipstick was
      applied evenly, and the lip print was obtained by dabbing a strip of cellophane.
      The classification scheme proposed by Tsuchihashi was used to classify the lip
      print patterns and the data were statistically analyzed using the z-test for
      proportions. RESULTS: Type 4 and Type 5 lip print patterns were predominant in
      males, whereas in females it was Type 1 and Type 1'. Type 1 pattern was most
      common in both the populations, with an incidence of 28.33%. Furthermore, Type 1
      pattern was found to be more in Kerala females and Manipuri males when compared
      to their counterparts. Type 1 was most common in upper right, upper left, and
      lower left quadrants whereas in lower right quadrant, Type 1' and Type 4 were
      predominant in Kerala and Type 5 in Manipuri population. CONCLUSION: Difference
      between the lip print patterns in two populations exists, although subtle.
      However, larger sample size is necessary to derive concrete conclusions.

PMID- 23960410
TI  - A comparative study of overlay generation methods in bite mark analysis.
AB  - AIM: To evaluate the best method of overlay generation out of the three methods,
      i.e., manual, photocopying, and computer assisted method. MATERIALS AND METHODS:
      Impressions of maxillary and mandibular arches of 25 individuals participating in
      the study were made and dental study models were prepared. Overlay production was
      done by manual, photocopying, and computer assisted methods. Finally, the
      overlays obtained by each method were compared. RESULTS: Kruskal Wallis ANOVA H
      test was used for the comparison of manual, photocopying, and computer assisted
      overlay generation methods. H value being highest in case of computer assisted
      overlays, thus, making it the best method of overlay generation out of the three
      methods. CONCLUSION: We conclude that the method of computer assisted overlay
      generation is the best among the three methods used in our study.

PMID- 23960411
TI  - Latent lip print development and its role in suspect identification.
AB  - AIMS AND OBJECTIVE: The study aims to develop latent lip prints on glass surface
      using fingerprint black powder and its comparison with standard lipstick prints
      and also determines the effectiveness of the technique. MATERIALS AND METHODS:
      This study included a total of 100 subjects, comprising of 50 males and 50
      females with age ranging from 17 to 38 years. Latent lipprint was developed by
      pressing the lips against a glass slab with lips together and the print formed
      was developed by sprinkling the black finger print powder and transferred to a
      bond sheet. Subsequently, standard lipstick print was developed from the same
      subject. All the samples were coded and graded according to the patterns
      suggested in the literature. RESULTS: Out of 100 latent prints only 29 prints
      showed lip patterns in all four quadrants. The percentage matching with self
      lipstick print of good latent prints ranged from 25% to 100% and those of random
      prints ranged from 8% to 92%. Quadrant wise matching ranged from 52.67% to
      57.67%. Statistically significant difference was observed between males and
      females. CONCLUSION: The study demonstrates the usefulness of latent lip print in
      personal identification.

PMID- 23960412
TI  - ABO blood grouping from hard and soft tissues of teeth by modified absorption
      elution technique.
AB  - BACKGROUND: Teeth have always been known as stable tissue that can be preserved
      both physically and chemically for long periods of time. Blood group substances
      have been known to be present in both the hard and soft tissues of the teeth.
      OBJECTIVES: This study aimed at detection of ABO blood group substances from soft
      and hard tissues of teeth and also to evaluate the reliability of teeth stored
      for a relatively long period as a source of blood group substances by absorption
      elution technique with some modifications. RESULTS: Blood group obtained from the
      teeth was compared with those obtained from the blood sample. Pulp showed a very
      large correlation in both fresh and long-standing teeth though it decreased
      slightly in the latter. Hard tissue showed a large correlation in both the groups
      indicating that hard tissue is quite reliable to detect blood group and that
      there is no much difference in the reliability in both the groups. However,
      combining pulp and hard tissue, correlation is moderate. Correlation of blood
      grouping with the age, sex, and jaw distribution was carried out. CONCLUSION:
      Blood group identification from hard and soft tissues of teeth aids in the
      identification of an individual.

PMID- 23960413
TI  - A study of composite restorations as a tool in forensic identification.
AB  - INTRODUCTION: Comparing ante-mortem and post-mortem dental data is a principal
      method of identification in forensic odontology. Radiographic images of amalgam
      have been used in dental forensics for identification due to their unique
      appearance. AIM: The aim of this study was to investigate whether radio-opaque
      composite restorations have a potential for identification in forensic
      odontology. MATERIALS AND METHODS: Thirty typodont mandibular first molar teeth
      were prepared with Class-II (proximo-occlusal) cavities and restored with a radio
      opaque composite (Tetric N-Ceram). Two sets of standardized radiographs were
      taken from the 30 teeth, keeping the radiological parameters constant. One set of
      these 30 radiographs was named as SET 1. Ten randomly chosen radiographs from the
      other set and two other radiographs of Class-II composite restorations in
      typodont teeth constituted SET 2. Thirty dentally trained examiners were asked to
      match the 12 radiographic images of SET 2 with those of SET 1. RESULTS: The
      results show that 15 examiners were able to correctly match all the 12 images.
      Statistical analysis was done using kappa statistical test. CONCLUSION: This
      study shows that, if the post-mortem radiographs are accurate duplicates of ante
      mortem radiographs of composite restorations, then the shape of the composite
      restoration is unique and can be used for identification.

PMID- 23960414
TI  - Assessment of morphological changes and DNA quantification: An in vitro study on
      acid-immersed teeth.
AB  - CONTEXT: Acid immersion of victim's body is one of the methods employed to
      subvert identification of the victim, and hence of the perpetrator. Being hardest
      and chemically the most stable tissue in the body, teeth can be an important
      forensic investigative medium in both living and nonliving populations. Teeth are
      also good reservoirs of both cellular and mitochondrial DNA; however, the quality
      and quantity of DNA obtained varies according to the environment the tooth has
      been subjected to. DNA extraction from acid-treated teeth has seldom been
      reported. AIMS: The objectives of the present study were to assess the
      morphological changes along with DNA recovery from acid-immersed teeth. MATERIALS
      AND METHODS: Concentrated hydrochloric acid, nitric acid, and sulfuric acid were
      employed for tooth decalcification. DNA was extracted on an hourly basis using
      phenol-chloroform method. Quantification of extracted DNA was done using a
      spectrophotometer. RESULTS: Results showed that hydrochloric acid had more
      destructive capacity compared to other acids. CONCLUSION: Sufficient quantity of
      DNA was obtainable till the first 2 hours of acid immersion and there was an
      inverse proportional relation between mean absorbance ratio and quantity of
      obtained DNA on an hourly basis.

PMID- 23960415
TI  - Digital approach for measuring dentin translucency in forensic age estimation.
AB  - BACKGROUND: Dentin translucency is best suited for age estimation not only in
      terms of accuracy but also in terms of simplicity. Conventionally, translucency
      has been measured using calipers. Computer-based methods have been proposed for
      the same, although these required the use of custom-built software programs.
      OBJECTIVES: The objectives of the study were to use a simple digital method to
      measure dentinal translucency on sectioned teeth and to compare digital
      measurements to conventionally obtained translucency measurements. MATERIALS AND
      METHODS: Fifty extracted permanent teeth were collected and were sectioned to 250
      MUm. Translucency measurements were obtained using the digital method and
      compared with those obtained using a caliper. RESULTS: Correlation coefficients
      of translucency measurements to age were statistically significant for both
      methods (P < 0.001), and marginally higher for the conventional approach (r =
      0.4671). Application of derived linear regression equations on an independent
      sample (n = 10) revealed a similar ability of both the methods to assess age to
      within +/-5 years of the actual age. CONCLUSION: The translucency measurements
      obtained by the two methods were very similar, with no clear superiority of one
      method over the other. Hence, further studies on a large scale are warranted to
      determine which method is more reliable to estimate the age.

PMID- 23960416
TI  - Determination of sex by radiographic analysis of mental foramen in North Indian
      population.
AB  - AIM: Identification and determination of sex of unknown human skeletal remains
      has been one of the most challenging tasks for forensic dentistry. The purpose of
      this study was to determine the gender from the analysis of mental foramen on
      panoramic radiographs in a north Indian population. MATERIALS AND METHODS: One
      hundred radiographs were selected for the analysis of mental foramen. Tangents
      were drawn to the superior and inferior borders of the foramen and perpendiculars
      were drawn from the tangents to the lower border of the mandible (S-L and I-L).
      The data obtained were tabulated and subjected to statistical analysis. RESULTS:
      The average values of S-L and I-L were significantly higher in males than in
      females, while the distances for the right and left sides of an individual were
      almost similar in both the male and the females group, and the results were non
      significant. CONCLUSION: The distances from the mental foramen to the lower
      border of the mandible exhibit sexual dimorphism in the north Indian population.

PMID- 23960417
TI  - Adult forensic age estimation using mandibular first molar radiographs: A novel
      technique.
AB  - OBJECTIVE: To develop an independent procedure for estimating age for Indian
      individuals using radiographs of multi-rooted posterior teeth with accuracy
      needed in forensic age prediction. MATERIALS AND METHODS: Orthopantomography
      (OPG) was obtained for 88 subjects. The subjects were divided into two sub sets;
      study subset (n = 60) which were used to find regression formula to calculate the
      age from pulp chamber height and test subset (n = 28) which were used to test the
      accuracy of this formula. RESULTS: There was a statistically significant strong
      correlation between chronological age and pulp chamber crown root trunk height
      ratio (r = -0.56; P = 0.000). The regression equation for estimating the age,
      derived from the study subset was estimated age = -100.920 (PCTHR) +55.415.
      (PCTHR is the pulp chamber crown root trunk height ratio). This equation was
      applied on the test subset and there was no significant difference between
      estimated ages and chronological ages (P = 0.639). The mean absolute error (MAE)
      was 6.96 years, which was within acceptable error limits for forensic age
      estimation (<+/-10 years). CONCLUSION: The procedure developed to estimate the
      age using height reduction in pulp chamber was found to be fairly accurate to
      perform forensic age prediction in Indian individuals.

PMID- 23960418
TI  - Denture identification using unique identification authority of India barcode.
AB  - Over the years, various denture marking systems have been reported in the
      literature for personal identification. They have been broadly divided into
      surface marking and inclusion methods. In this technique, patient's unique
      identification number and barcode printed in the patient's Aadhaar card issued by
      Unique Identification Authority of India (UIDAI) are used as denture markers.
      This article describes a simple, quick, and economical method for identification
      of individual. 

PMID- 23960419
TI  - Barr bodies in sex determination.

PMID- 23960420
TI  - Improving quality of medical education in India: The need to value and recognize
      academic scholarship.

PMID- 23960421
TI  - The metabolic syndrome and schizophrenia: A comorbidity or an association?

PMID- 23960423
TI  - N-acetyl cysteine in clomiphene citrate resistant polycystic ovary syndrome: A
      review of reported outcomes.
AB  - Clomiphene citrate (CC) has been the gold-standard drug for ovulation induction
      in polycystic ovary syndrome (PCOS), but still CC resistance is seen in
      approximately 15-40% in women with PCOS. N-acetyl cysteine (NAC), a safe and
      cheap drug available in the market many years ago as mucolytic agent, was found
      to have a role in infertility management. Recently, some reports discussed the
      possible beneficial effects of NAC on ovulation. The biological properties of the
      NAC make this drug a potential candidate for its use in the infertility
      treatment, especially in the PCOS in inducing or augmenting ovulation. An updated
      electronic search was performed through PUBMED, MEDLINE, and COCHRANE and focused
      on peer-reviewed, full text, randomized controlled trials, and observational
      cohort or case-control studies for role of NAC in CC-resistant PCOS. Thorough
      search through all the clinical studies showed mixed results. Studies with
      positive results showed improvement in induction of ovulation as compared to
      negative studies showing contrary results. More randomized clinical trials are
      still needed to establish its definitive role in CC-resistant PCOS. 

PMID- 23960424
TI  - Neuroprotective role of naringenin on carbaryl induced neurotoxicity in mouse
      neuroblastoma cells.
AB  - OBJECTIVE: Neuroprotective effect of naringenin against carbaryl toxicity was
      studied in mouse neuroblastoma cell line. MATERIALS AND METHODS: Mouse
      neuroblastoma cells (Neuro 2A) obtained from National Center for Cell Sciences,
      Pune, India were either exposed to carbaryl or pre-treated with naringenin (a
      flavonoid prepared from grape fruit) before their exposure to carbaryl. Results
      were analyzed using MTT [3-4,5-Dimethylthiazol-2-yl)-2,5-diphenltetrazolium
      bromide] assay for cell viability, FACS (fluorescence assisted cell sorting)
      analysis for apoptotic and necrotic cell populations, DCFH-DA (2',7'
      dichlorofluorescin-diacetate) assay for Reactive Oxygen Species (ROS)
      visualization, JC-1 staining for determining mitochondrial membrane potential and
      real-time PCR for quantifying pro and anti-apoptotic gene expression. RESULTS:
      Exposure to naringenin resulted in better survival of Neuro 2A cells which were
      subsequently subjected to carbaryl toxicity. Treatment with naringenin was found
      to reduce the oxidative stress by decreasing the ROS and was found to maintain
      the integrity of mitochondrial membrane potential. It was also found to
      downregulate pro-apoptotic genes (BAX and Caspase-3) while upregulating anti
      apototic gene (Bcl2). CONCLUSION: The results of this pilot study underline the
      potential of naringenin in treating carbaryl induced neurotoxicity and further
      studies are warranted to establish the effect of naringenin in vivo conditions.

PMID- 23960422
TI  - Metabolic syndrome in schizophrenia: Differences between antipsychotic-naive and
      treated patients.
AB  - Metabolic syndrome (MetS) has been recognized as a risk factor for cardiovascular
      morbidity and mortality in general population and in patients with severe mental
      illnesses like schizophrenia. This paper reviews studies on MetS in schizophrenia
      and related psychotic disorders, and assesses the contribution of antipsychotics
      toward the development of MetS. Databases of Medline (PubMed), PsycINFO, and
      Scopus were searched for MetS, psychotic disorders, and antipsychotic drugs from
      inception till present. Prevalence of MetS in patients with schizophrenia was
      found to be ranging from 3.3% to 68.0%. Prevalence in antipsychotic-naive and
      antipsychotic-treated patients ranged between 3.3-26.0% and 32.0-68.0%
      respectively, and was higher in younger patients, female gender and Hispanics,
      and lower in African-Americans and Orientals. Prevalence of metabolic
      abnormalities was higher in patients receiving second generation antipsychotics
      (SGAs), especially with clozapine, olanzapine, and risperidone, as compared to
      first generation antipsychotics (FGAs). Antipsychotic-induced changes on
      metabolic indices became evident after 2 weeks and reached maximum at 3 months of
      treatment. There is a need to sensitize the mental health professionals at all
      levels about the need of screening and monitoring for MetS in patients receiving
      antipsychotics. 

PMID- 23960425
TI  - Effects of structural analogues of apelin-12 in acute myocardial infarction in
      rats.
AB  - OBJECTIVE: To examine cardioprotective effects of Rho-terminal fragment of
      adipokine apelin-12 (A12), its novel structural analogue [MeArg(1), NLe(10)]-A12
      (I), and [d-Ala(12)]-A12 (II), a putative antagonist of APJ receptor, employing
      in vivo model of ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS:
      Peptides were synthesized by the automatic solid phase method using Fmoc
      technology. Anesthetized open-chest male Wistar rats were subjected to left
      anterior descending (LAD) coronary artery occlusion and coronary reperfusion.
      Hemodynamic variables and electrocardiogram (ECG) were monitored throughout the
      experiment. Myocardial injury was assessed by infarct size (IS), activity of
      necrosis markers in plasma, and metabolic state of the area at risk (AAR).
      RESULTS: Intravenous injection of A12, I, or II at the onset of reperfusion led
      to a transient reduction of the mean arterial pressure. A12 or I administration
      decreased the percent ratio of IS/AAR by 40% and 30%, respectively, compared with
      control animals which received saline. Both peptides improved preservation of
      high-energy phosphates, reduced lactate accumulation in the AAR, and lowered CK
      MB and LDH activities in plasma at the end of reperfusion compared with these
      indices in control. Treatment with II did not significantly affect either the
      IS/AAR, % ratio, or activities of both markers of necrosis compared with control.
      The overall metabolic protection of the AAR in the treated groups increased in
      the following rank: II < A12 < I. CONCLUSIONS: The structural analogue of apelin
      12 [MeArg(1), NLe(10)]-A12 may be a promising basis to create a new drug for the
      treatment of acute coronary syndrome.

PMID- 23960426
TI  - Audit of use of antibiotics and zinc supplement in childhood diarrhea.

PMID- 23960427
TI  - Comparison of efficacy of Saccharomyces boulardii strain in the treatment of
      acute diarrhea in children: A prospective, single-blind, randomized controlled
      clinical trial.

PMID- 23960428
TI  - Modulation of inflammatory pain in response to a CCR2/CCR5 antagonist in rodent
      model.

PMID- 23960429
TI  - An experimental spinal cord injury rat model using customized impact device: A
      cost-effective approach.
AB  - Till date, NYU MASCIS (New York University, Multicenter Animal Spinal Cord Injury
      Study) impactor and Ohio State University electromagnetic spinal cord injury
      device impactor were under use for simulating an experimental spinal cord injury
      in rodents; functional recovery being assessed through Basso, Beattie and
      Bresnahan (BBB) scoring method which is an open field behavior based scoring
      system. Although, the cited impactors are state-of-art devices, affordability to
      scientists in developing and under developed countries is questionable. Since the
      acquisition of these impact devices are expensive, we designed a customized
      impact device based on the requirement, satisfying all the parameters to
      withstand a standard animal model for contusion type of spinal cord injury at the
      thoracic level without compromising the lesion reproducibility. Here, a spinal
      cord contusion is created using a blunt-force impactor in male Wistar rats. Our
      method gave consistent lesion effects as evaluated by behavior scoring methods.
      All the animals showed equal degree of performance in tests like narrow beam,
      inclined plane and horizontal ladder and in BBB scores (open field locomotor
      test). The aim of presenting our experience is to reinstate the fact that lack of
      affordability to get sophisticated instrumentation need not be a hurdle in the
      pursuit of science. 

PMID- 23960430
TI  - Pseudocyesis: A complication of antipsychotic-induced increased prolactin levels
      and weight gain.
AB  - Pseudocyesis or phantom pregnancy is characterized by a false belief in a non
      pregnant female that she is pregnant and this belief is usually associated with
      bodily signs of pregnancy. In some of the patients, this belief is held with
      delusional conviction. In this case report, we present the case of a female
      patient who presented with delusional belief of being pregnant, which was
      associated with antipsychotic-associated increase in prolactin levels and
      metabolic syndrome. 

PMID- 23960431
TI  - Additive effect of propofol and fentanyl precipitating cardiogenic shock.
AB  - The intravenous administration of propofol and fentanyl has become a common
      practice in a variety of clinical settings including outpatient dermatologic,
      cosmetic and oral surgery. The combination provides both systematic sedation and
      analgesia with low incidence of unwanted side effects. The cardiogenic shock is
      very uncommon in healthy individuals. The cardiovascular depressive effect of
      propofol and fentanyl has been well established, but the development of
      cardiogenic shock is very rare when these drugs are used together. Hence the
      awareness of this effect is advantageous to the patients undergoing such
      surgeries. 

PMID- 23960432
TI  - Good! Is it the best???

PMID- 23960433
TI  - Reply to "Good! is it the best ???

PMID- 23960434
TI  - Choosing the target journal: do authors need a comprehensive approach?

PMID- 23960435
TI  - Global trends in medical journal publishing.

PMID- 23960436
TI  - Associations between cigarette smoking and total mortality differ depending on
      serum concentrations of persistent organic pollutants among the elderly.
AB  - There are substantial variations of relative risks (RR) in smoking-related
      mortality by country and time. We hypothesized the RRs in smoking-related
      mortality might differ depending on serum concentrations of persistent organic
      pollutants (POPs). We evaluated the associations of cigarette smoking with total
      mortality in 610 elderly (aged >= 70 yr) (702 elderly for organochlorine
      pesticides [OCPs]) after stratification by serum concentration of POPs, in the
      National Health and Nutrition Examination Survey (NHANES) 1999-2004 followed
      through 2006. Summary measures of POPs subclasses showed significant or
      marginally significant interaction with cigarette smoking on the risk of total
      mortality. P values for interaction were 0.069 for polychlorinated dibenzo-p
      dioxins (PCDDs), 0.008 for polychlorinated biphenyls (PCBs), and 0.024 for OCPs.
      The effect of smoking on total mortality showed different patterns according to
      the serum concentration of some POPs. Former or current smokers had 1.4 to 2.9
      times higher mortality rates compared with never smokers among participants with
      higher serum concentrations of POPs (2nd or 3rd tertiles). However, when the
      level of PCBs or OCPs were low (1st tertile), there were little positive
      associations between smoking and mortality. Our study suggests that the
      background exposure to several POPs may be related to variability in smoking
      related total mortality. 

PMID- 23960437
TI  - Screening of dihydropyrimidine dehydrogenase genetic variants by direct
      sequencing in different ethnic groups.
AB  - Dihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates the rate
      limiting step in pyrimidine metabolism, especially catabolism of fluorouracil, a
      chemotherapeutic agent for cancer. In order to determine the genetic distribution
      of DPYD, we directly sequenced 288 subjects from five ethnic groups (96 Koreans,
      48 Japanese, 48 Han Chinese, 48 African Americans, and 48 European Americans). As
      a result, 56 polymorphisms were observed, including 6 core polymorphisms and 18
      novel polymorphisms. Allele frequencies were nearly the same across the Asian
      populations, Korean, Han Chinese and Japanese, whereas several SNPs showed
      different genetic distributions between Asians and other ethnic populations
      (African American and European American). Additional in silico analysis was
      performed to predict the function of novel SNPs. One nonsynonymous SNP (+199381A
      > G, Asn151Asp) was predicted to change its polarity of amino acid (Asn, neutral
      to Asp, negative). These findings would be valuable for further research,
      including pharmacogenetic and drug responses studies. 

PMID- 23960438
TI  - Tofacitinib prevents radiographic progression in rheumatoid arthritis.
AB  - Tofacitinib, a novel Janus kinase inhibitor, may prevent structural damage in
      rheumatoid arthritis (RA). In this cohort study, we compared radiographic
      progression of hand joints between 21 RA patients who took tofacitinb for 18
      months in a phase IIb and its extension study and 42 patients who took
      conventional disease modifying antirheumatic drugs (DMARDs), using simple erosion
      narrowing score. For tofacitinib group, changes before and after the treatment
      were also compared. The changes of erosion and sum scores were significantly less
      in tofacitinib than DMARDs group (for erosion, -0.60 +/- 1.83 vs 0.51 +/- 1.77, P
      = 0.038; for sum, -0.50 +/- 1.72 vs 1.57 +/- 4.13, P = 0.012). Joint space
      narrowing score (JSN) was also less in tofacitinib group (0.095 +/- 0.58 vs 1.06
      +/- 2.60, P = 0.055). In tofacitinib group, yearly rates of both erosion and JSN
      were significantly decreased after administration of tofacitinib (For erosion,
      0.62 +/- 0.93 to -0.14 +/- 0.48, P = 0.009; for JSN, 0.47 +/- 0.64 to 0.03 +/-
      0.40, P = 0.032), as was change of sum score (1.09 +/- 1.27 to -0.10 +/- 0.63, P
      < 0.001). In conclusion, tofacitinib may prevent structural damage caused by RA. 

PMID- 23960439
TI  - The effects of antihypertensive drugs on bone mineral density in ovariectomized
      mice.
AB  - The effects of several antihypertensive drugs on bone mineral density (BMD) and
      micro-architectural changes in ovariectomized (OVX) mice were investigated. Eight
      week-old female C57/BL6 mice were used for this study. Three days after
      ovariectomy, mice were treated intraperitoneally with nifedipine (15 mg/kg),
      telmisartan (5 mg/kg), enalapril (20 mg/kg), propranolol (1 mg/kg) or
      hydrochlorothiazide (12.5 mg/kg) for 35 consecutive days. Uterine atrophy of all
      mice was confirmed to evaluate estrogen deficiency state. BMD and micro
      architectural analyses were performed on tibial proximal ends by micro-computed
      tomography (micro-CT). When OVX mice with uterine atrophy were compared with mice
      without atrophy, BMD decreased (P < 0.001). There were significant differences in
      BMD loss between different antihypertensive drugs (P = 0.005). Enalapril and
      propranolol increased BMD loss in mice with atrophied uteri compared with control
      mice. By contrast, thiazide increased BMD in mice with uterine atrophy compared
      with vehicle-treated mice (P = 0.048). Thiazide (P = 0.032) and telmisartan (P =
      0.051) reduced bone loss and bone fraction in mice with uterine atrophy compared
      with the control. Thiazide affects BMD in OVX mice positively. The reduction in
      bone loss by thiazide and telmisartan suggest that these drugs may benefit
      menopausal women with hypertension and osteoporosis. 

PMID- 23960440
TI  - Serum level of interleukin-33 and soluble ST2 and their association with disease
      activity in patients with Behcet's disease.
AB  - Interleukin (IL)-33 is an important mediator of innate immunity. Behcet's disease
      (BD) is an autoinflammatory disorder characterized by hyperactivity of the innate
      immune response. We measured serum levels of IL-33 and its receptor soluble ST2
      (sST2) in patients with BD to investigate their association with disease
      activity. Serum levels of both IL-33 and sST2 were higher in patients with BD
      compared with those in normal controls (IL-33: 594.48+/-175.04 pg/mL in BD and
      224.23+/-56.64 pg/mL in normal controls [P=0.048], sST2: 99.01+/-15.92 pg/mL in
      BD and 23.56+/-3.25 pg/mL in normal controls [P<0.001]). IL-33 and sST2
      expression in skin tissue, as shown by immunohistochemistry, was higher in
      patients with BD compared with that in the normal controls. Serum sST2 level
      correlated significantly with the BD currently active form (BDCAF), Iranian BD
      dynamic activity measure (IBDDAM), erythrocyte sedimentation rate and C-reactive
      protein. Multiple linear regression showed that serum sST2 was an independent
      factor associated with IBBDAM (regression coefficient, 0.374; P=0.004), and BDCAF
      (regression coefficient, 0.236; P=0.047). These results demonstrate that IL-33
      and sST2 are highly expressed in patients with BD and that serum sST2 is an
      independent factor associated with IBDDAM and BDCAF, suggesting a potential role
      for sST2 as a surrogate marker of disease activity in patients with BD. 

PMID- 23960441
TI  - 15-hydroxyprostaglandin dehydrogenase in colorectal mucosa as a potential
      biomarker for predicting colorectal neoplasms.
AB  - 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is downregulated during the early
      stages of colorectal carcinogenesis. The aim of the present study was to
      investigate the potential role of 15-PGDH in normal-appearing colorectal mucosa
      as a biomarker for predicting colorectal neoplasms. We obtained paired tumor and
      normal tissues from the surgical specimens of 32 sporadic colorectal cancer
      patients. mRNA expression of 15-PGDH was measured using a quantitative real-time
      PCR assay. We evaluated the association between 15-PGDH mRNA expression in normal
      appearing mucosa, the presence of synchronous adenoma, and the cumulative
      incidence of metachronous adenoma. The relative 15-PGDH expression of normal
      appearing mucosa in patients with synchronous adenoma was significantly lower
      than in patients without synchronous adenoma (0.71 vs 1.00, P = 0.044). The
      patients in the lowest tertile of 15-PGDH expression in normal-appearing mucosa
      were most likely to have synchronous adenoma (OR: 10.5, P = 0.024). Patients with
      low 15-PGDH expression in normal-appearing mucosa also demonstrated more advanced
      stage colorectal cancer (P = 0.045). However, there was no significant difference
      in the cumulative incidence of metachronous adenoma according to 15-PGDH mRNA
      expression in normal-appearing mucosa (P = 0.333). Hence, 15-PGDH in normal
      appearing colorectal mucosa can be a useful biomarker of field effect for the
      prediction of sporadic synchronous neoplasms. 

PMID- 23960442
TI  - An integrative model of the cardiovascular system coupling heart cellular
      mechanics with arterial network hemodynamics.
AB  - The current study proposes a model of the cardiovascular system that couples
      heart cell mechanics with arterial hemodynamics to examine the physiological role
      of arterial blood pressure (BP) in left ventricular hypertrophy (LVH). We
      developed a comprehensive multiphysics and multiscale cardiovascular model of the
      cardiovascular system that simulates physiological events, from membrane
      excitation and the contraction of a cardiac cell to heart mechanics and arterial
      blood hemodynamics. Using this model, we delineated the relationship between
      arterial BP or pulse wave velocity and LVH. Computed results were compared with
      existing clinical and experimental observations. To investigate the relationship
      between arterial hemodynamics and LVH, we performed a parametric study based on
      arterial wall stiffness, which was obtained in the model. Peak cellular stress of
      the left ventricle and systolic blood pressure (SBP) in the brachial and central
      arteries also increased; however, further increases were limited for higher
      arterial stiffness values. Interestingly, when we doubled the value of arterial
      stiffness from the baseline value, the percentage increase of SBP in the central
      artery was about 6.7% whereas that of the brachial artery was about 3.4%. It is
      suggested that SBP in the central artery is more critical for predicting LVH as
      compared with other blood pressure measurements. 

PMID- 23960443
TI  - Evaluation of cardiovascular anomalies in patients with asymptomatic turner
      syndrome using multidetector computed tomography.
AB  - Turner syndrome is well known to be associated with significant cardiovascular
      abnormalities. This paper studied the incidence of cardiovascular abnormalities
      in asymptomatic adolescent patients with Turner syndrome using multidetector
      computed tomography (MDCT) instead of echocardiography. Twenty subjects diagnosed
      with Turner syndrome who had no cardiac symptoms were included. Blood pressure
      and electrocardiography (ECG) was checked. Cardiovascular abnormalities were
      checked by MDCT. According to the ECG results, 11 had a prolonged QTc interval, 5
      had a posterior fascicular block, 3 had a ventricular conduction disorder. MDCT
      revealed vascular abnormalities in 13 patients (65%). Three patients had an
      aberrant right subclavian artery, 2 had dilatation of left subclavian artery, and
      others had an aortic root dilatation, aortic diverticulum, and abnormal left
      vertebral artery. As for venous abnormalities, 3 patients had partial anomalous
      pulmonary venous return and 2 had a persistent left superior vena cava. This
      study found cardiovascular abnormalities in 65% of asymptomatic Turner syndrome
      patients using MDCT. Even though, there are no cardiac symptoms in Turner
      syndrome patients, a complete evaluation of the heart with echocardiography or
      MDCT at transition period to adults must be performed. 

PMID- 23960444
TI  - Risk factors between patients with lone and non-lone atrial fibrillation.
AB  - Clinical factors such as tall stature, lean body mass, obstructive sleep apnea,
      alcohol or caffeine, smoking, endurance sports, and genetic factors are proposed
      as risk factors for lone atrial fibrillation (LAF). The KORAF (KORean Atrial
      Fibrillation) study is a retrospective multicenter registry that enrolled 3,570
      consecutive atrial fibrillation (AF) patients. Data on risk factors were
      available for 2,133 patients, of whom 398 (18.7%) were identified as having LAF.
      In univariate analysis, patients with LAF were more likely to be men (82.4% vs
      59.8%, P < 0.001) and current smokers (25.9% vs 15.6%, P < 0.01), alcohol
      drinkers (55.3% vs 31.2%, P < 0.01) and frequent consumers of caffeinated
      beverages (> 2 cups/day) (31.7% vs 19.3%, P < 0.01), and have a family history of
      AF (9.0% vs 2.6%, P < 0.001) than the non-LAF patients. Multivariate analysis
      showed that male gender (OR, 2.30; 95% CI, 1.61-3.27, P < 0.01), family history
      of AF (OR, 3.12; 95% CI, 1.91-5.12, P < 0.01), current alcohol use (OR, 2.01; 95%
      CI, 1.46-2.76, P < 0.01), and frequent caffeinated beverage consumption (OR,
      1.66; 95% CI, 1.20-2.29, P < 0.01) were independently associated with LAF. In
      Korean patients, LAF is more closely associated with male gender, family history
      of AF, current alcohol and frequent caffeinated beverage consumption than non
      LAF. 

PMID- 23960445
TI  - Urinary biomarkers for early detection of recovery in patients with acute kidney
      injury.
AB  - Urinary biomarkers of acute kidney injury (AKI) have been revealed recently to be
      useful for prior prediction of AKI. However, it is unclear whether these urinary
      biomarkers can also detect recovery from established AKI. Urinary biomarkers,
      including neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, were
      measured every 2 days for 8 days in 66 patients with AKI. At day 0, there were no
      significant differences in plasma creatinine, BUN, and urine cystatin C between
      AKI patients in the recovery (n = 33) and non-recovery (n = 33) groups. Plasma
      creatinine concentrations were significantly lower in the recovery group (3.0 +/-
      2.0 mg/dL) than in the non-recovery group (5.4 +/- 1.9 mg/dL) on day 4 after AKI
      diagnosis (P < 0.001). In contrast, there were significant differences in urine
      NGAL between the two groups starting on day 0 (297.2 +/- 201.4 vs 407.6 +/- 190.4
      ng/mL, P = 0.025) through the end of the study (123.7 +/- 119.0 vs 434.3 +/-
      121.5 ng/mL, P < 0.001). The multiple logistic regression analysis showed that
      urine NGAL could independently predict recovery from AKI. Conclusively, this
      prospective observational study demonstrates that urine NGAL can be a highly
      versatile marker for early detection of the recovery phase in established AKI
      patients. 

PMID- 23960446
TI  - Higher Prevalence of Klebsiella pneumoniae Extended-Spectrum beta-Lactamase in
      Patients on Renal Replacement Therapy.
AB  - The prevalence of antibiotic resistance is higher in patients undergoing renal
      replacement therapy (RRT) than in patients who did not undergo RRT. We
      investigated the presence of KP (Klebsiella pneumoniae) in patients who underwent
      RRT. All data were collected retrospectively by accessing patient medical records
      from 2004 to 2011 for the culture results of all patients who were positive for
      KP. We grouped the patients by the presence of extended-spectrum beta-lactamase
      (ESBL) into a KP ESBL(-) group (KP[-]) and a KP ESBL(+) group (KP[+]). In total,
      292 patients (23.1%) were in the KP(+) group, and 974 patients (76.9%) were in
      the KP(-) group. A greater percentage of KP(+) was found in patients who
      underwent RRT (7.5%) than in patients who did not undergo RRT (3.2%) (OR, 2.479;
      95% CI,1.412-4.352). A Cox's hazard proportional model analysis was performed,
      and for patients with pneumonia, the risk of KP(+) was 0.663 times higher in
      patients who had lower albumin levels, 2.796 times higher in patients who had an
      inserted Levin tube, and 4.551 times higher in patients who underwent RRT. In
      conclusion, RRT can be a risk factor for KP(+) in patients with pneumonia. 

PMID- 23960447
TI  - Incidence, etiology, and outcomes of rhabdomyolysis in a single tertiary referral
      center.
AB  - We have encountered numerous cases of rhabdomyolysis associated with acute
      pesticide intoxication; however, the cause, incidence, and treatment outcomes of
      rhabdomyolysis have not been studied. The current study involved 2,125 patients
      hospitalized with acute chemical poisoning. Based on clinical and laboratory
      parameters and treatment outcomes, we found that overall incidence of
      rhabdomyolysis in our hospital was 0.06% (93 of 143,830 patients admitted), but
      the incidence associated with acute pesticide intoxication was 1.8% (33 of 1,793
      cases). The incidence of rhabdomyolysis after pesticide intoxication was
      significantly higher in men than in women (P = 0.010). The amount of pesticide
      ingested was significantly higher in rhabdomyolysis patients than that in those
      who did not develop rhabdomyolysis (mean +/- SD, 114.1 +/- 79.5 mL vs 74.1 +/-
      94.2 mL, P = 0.010). Our results show that pesticide intoxication is a frequent
      cause of rhabdomyolysis and is more common among men than women. The volume of
      pesticide ingested, and not the degree of human toxicity, is the main factor
      influencing the incidence of rhabdomyolysis. 

PMID- 23960448
TI  - Systematic review and meta-analysis of pulmonary hypertension specific therapy
      for exercise capacity in chronic obstructive pulmonary disease.
AB  - Some patients with chronic obstructive pulmonary disease (COPD) have pulmonary
      hypertension (PH) that adversely affects survival. We performed a systematic
      review and meta-analysis to assess whether PH-specific therapies have an effect
      for stable COPD. Data sources were Medline, EMBASE, Cochrane Central Register of
      Controlled Trials, Korea med and references from relevant publications.
      Randomized prospective trials that compared PH specific therapy in COPD for more
      than 6 weeks with placebo were included. The outcomes were the exercise capacity
      and adverse events. Four randomized controlled trials involving 109 subjects were
      included in the analysis. Two trials involved bosentan, one sildenafil and one
      beraprost. The studies varied in duration of treatment from 3 to 18 months. In a
      pooled analysis of four trials, exercise-capacity was not significantly improved
      with PH-specific treatment for COPD (risk ratio, -5.1; 95% CI, -13.0 to 2.8).
      COPD with overt PH significantly improved the exercise capacity (mean difference,
      111.6; 95% CI, 63.3 to 159.9) but COPD with PH unknown did not (mean difference,
      26.6; 95% CI, -24.3 to 77.5). There was no significant difference in hypoxemia
      (mean difference, 2.6; 95% CI, -3.7 to 8.8). PH specific treatments have a
      significant effect in improving exercise capacity in COPD with overt PH. 

PMID- 23960449
TI  - The model for end-stage liver disease score-based system predicts short term
      mortality better than the current Child-Turcotte-Pugh score-based allocation
      system during waiting for deceased liver transplantation.
AB  - To adopt the model for end-stage liver disease (MELD) score-based system in
      Korea, the feasibility should be evaluated by analysis of Korean database. The
      aim of this study was to investigate the feasibility of the MELD score-based
      system compared with the current Child-Turcotte-Pugh (CTP) based-system and to
      suggest adequate cut-off to stratify waiting list mortality among Korean
      population. We included 788 adult patients listed in waiting list in Seoul
      National University Hospital from January 2008 to May 2011. The short-term
      survival until 6 months after registration was evaluated. Two hundred forty six
      (31.2%) patients underwent live donor liver transplantation and 353 (44.8%)
      patients were still waiting and 121 (15.4%) patients were dropped out due to
      death. Significant difference was observed when MELD score 24 and 31 were used as
      cut-off. Three-months survival of Status 2A was 70.2%. However, in Status 2A
      patients whose MELD score less than 24 (n=82), 86.6% of patients survived until 6
      month. Furthermore, patients with high MELD score (>=31) among Status 2B group
      showed poorer survival rate (45.8%, 3-month) than Status 2A group. In conclusion,
      MELD score-based system can predict short term mortality better and select more
      number of high risk patients in Korean population. 

PMID- 23960450
TI  - The impact of inosine triphosphatase variants on hemoglobin level and sustained
      virologic response of chronic hepatitis C in Korean.
AB  - TWO VARIANTS OF THE INOSINE TRIPHOSPHATASE (ITPA: rs1127354, rs7270101) gene
      cause ITPA deficiency and protect against the hemolytic toxicity of ribavirin. We
      investigated the clinical significance of ITPA variants in Korean patients
      treated with pegylated interferon (PEG-IFN) plus ribavirin. Of the 133 patients,
      108 were CC and 25 were non-CC at rs1127354 (groups A and B, respectively). On
      the other hand, at rs7270101 all 133 were AA. The mean values of Hemoglobin (Hgb)
      after 4, 8, and 12 weeks of treatment in groups A and B were 12.2 and 14.0, 11.8
      and 13.2, and 11.5 and 12.9, respectively (P=0.001, 0.036, 0.036). Sustained
      virologic response (SVR) was achieved in 67.8% (40/59) of genotype 1 patients and
      in 75% (27/36) of non-genotype 1 patients. Regarding ITPA variants, SVR was
      achieved by 66% and 80% of genotype 1 (P=0.282), and by 78% and 71% (P=0.726) of
      non-genotype 1. SVR was not significantly different in groups A and B. In
      conclusion, non-CC at rs1127354 without involvement of rs7270101 is strongly
      associated with protection from ribavirin-induced anemia, however, ITPA genotype
      is not associated with SVR.

PMID- 23960451
TI  - Optimal duration of medical treatment in superior mesenteric artery syndrome in
      children.
AB  - The aim of this study was to investigate the outcome, and optimal duration of
      medical treatment in children with superior mesenteric artery syndrome (SMAS).
      Eighteen children with SMAS were retrospectively studied. The data reviewed
      included demographics, presenting symptoms, co-morbid conditions, clinical
      courses, nutritional status, treatments, and outcomes. The three most common
      symptoms were postprandial discomfort (67.7%), abdominal pain (61.1%), and early
      satiety (50%). The median duration of symptoms before diagnosis was 68 days. The
      most common co-morbid condition was weight loss (50%), followed by growth spurt
      (22.2%) and bile reflux gastropathy (16.7%). Body mass index (BMI) was normal in
      72.2% of the patients. Medical management was successful in 13 patients (72.2%).
      The median duration of treatment was 45 days. Nine patients (50%) had good
      outcomes without recurrence, 5 patients (27.8%) had moderate outcomes, and 4
      patients (22.2%) had poor outcomes. A time limit of >6 weeks for the duration of
      medical management tended to be associated with worse outcomes (P=0.018). SMAS
      often developed in patients with normal BMI or no weight loss. Medical treatment
      has a high success rate, and children with SMAS should be treated medically for
      at least 6 weeks before surgical treatment is considered. 

PMID- 23960452
TI  - Intra-amniotic infection/inflammation as a risk factor for subsequent ruptured
      membranes after clinically indicated amniocentesis in preterm labor.
AB  - The aim of this study was to determine whether intra-amniotic
      infection/inflammation (IAI) was associated with subsequent ruptured membranes in
      women with preterm labor and intact membranes who had a clinically indicated
      amniocentesis. This retrospective cohort study included 237 consecutive women
      with preterm labor (20-34.6 weeks) who underwent amniocentesis. The clinical and
      laboratory parameters evaluated included demographic variables, gestational age,
      C-reactive protein (CRP) and amniotic fluid (AF) white blood cell, interleukin-6
      (IL-6) and culture results. IAI was defined as a positive AF culture and/or an
      elevated AF IL-6 level (>2.6 ng/mL). The primary outcome was ruptured membranes
      in the absence of active labor occurring within 48 hours of amniocentesis.
      Preterm premature rupture of membranes subsequently developed in 10 (4.2%) women
      within 48 hr of amniocentesis. Multivariate analysis demonstrated that only IAI
      was independently associated with the ruptured membranes occurring within 48 hr
      of amniocentesis. In the predictive model based on variables assessed before
      amniocentesis, only CRP level was retained. IAI is an independent risk factor for
      subsequent ruptured membranes after clinically indicated amniocentesis in preterm
      labor. Prior to amniocentesis, measurement of serum CRP level can provide a risk
      assessment for the subsequent development of ruptured membranes after the
      procedure. 

PMID- 23960453
TI  - Interfractional variation of radiation target and adaptive radiotherapy for
      totally resected glioblastoma.
AB  - This study aimed to evaluate the effects of volume adapted re-planning for
      radiotherapy (RT) after gross total resection (GTR) for glioblastoma. Nineteen
      patients with glioblastoma who underwent GTR and postoperative RT were analyzed.
      The volumes of the surgical cavity on computed tomography (CT) obtained one day
      after GTR (CT0), the first RT simulation CT (sim-CT1), and the second simulation
      CT for the boost RT plan (sim-CT2) were compared. The boost RT plan was based on
      the surgical cavity observed on the sim-CT2 (boost RTP2) and was compared with
      that based on the surgical cavity observed on the sim-CT1 (boost RTP1). The
      volume reduction ratios were 14.4%-51.3% (median, 29.0%) between CT0 and sim-CT1
      and -7.9%-71.9% (median, 34.9%) between sim-CT1 and sim-CT2 (P < 0.001). The
      normal brain volumes in boost RTP1 were significantly reduced in boost RTP2,
      especially at high dose levels. Target volume in sim-CT2 which was not covered
      with the boost RTP1, developed in five cases (26.3%). The surgical cavity volume
      was reduced following surgery in patients with glioblastoma who underwent GTR.
      The application of volume-adapted re-planning during RT could decrease the
      irradiated volume of normal brain and prevent a target miss for boost RT. 

PMID- 23960454
TI  - Antinociceptive effects of amiloride and benzamil in neuropathic pain model rats.
AB  - Amiloride and benzamil showed antinocicepitve effects in several pain models
      through the inhibition of acid sensing ion channels (ASICs). However, their role
      in neuropathic pain has not been investigated. In this study, we investigated the
      effect of the intrathecal amiloride and benzamil in neuropathic pain model, and
      also examined the role of ASICs on modulation of neuropathic pain. Neuropathic
      pain was induced by L4-5 spinal nerve ligation in male Sprague-Dawley rats
      weighing 100-120 g, and intrathecal catheterization was performed for drug
      administration. The effects of amiloride and benzamil were measured by the paw
      withdrawal threshold to a mechanical stimulus using the up and down method. The
      expression of ASICs in the spinal cord dorsal horn was also analyzed by RT-PCR.
      Intrathecal amiloride and benzamil significantly increased the paw withdrawal
      threshold in spinal nerve-ligated rats (87%+/-12% and 76%+/-14%, P=0.007 and
      0.012 vs vehicle, respectively). Spinal nerve ligation increased the expression
      of ASIC3 in the spinal cord dorsal horn (P=0.01), and this increase was inhibited
      by both amiloride and benzamil (P<0.001 in both). In conclusion, intrathecal
      amiloride and benzamil display antinociceptive effects in the rat spinal nerve
      ligation model suggesting they may present an alternative pharmacological tool in
      the management of neuropathic pain at the spinal level. 

PMID- 23960455
TI  - Effectiveness of mechanical embolectomy for septic embolus in the cerebral artery
      complicated with infective endocarditis.
AB  - There has been a controversy over data of thrombolytic and endovascular surgical
      treatment about cerebral infarction secondary to infective endocarditis. We
      report a woman who received early mechanical embolectomy as a treatment of acute
      stroke with infective endocarditis. A 35-yr-old woman was hospitalized due to
      right hemiparesis. Brain image showed cerebral infarction at the middle cerebral
      artery and echocardiography demonstrated vegetation at the mitral valve. She was
      successfully treated with embolectomy and parenteral antibiotics without any
      neurologic sequelae. This report shows that the early retrieve of septic cerebral
      emboli can be a helpful treatment of acute stroke associated with endocarditis. 

PMID- 23960456
TI  - Imatinib plasma monitoring-guided dose modification for managing imatinib-related
      toxicities in gastrointestinal stromal tumor patients.
AB  - Imatinib, the first-line treatment in patients with advanced gastrointestinal
      stromal tumors (GIST), is generally well tolerated, although some patients have
      difficulty tolerating the standard dose of 400 mg/day. Adjusting imatinib dosage
      by plasma level monitoring may facilitate management of patients who experience
      intolerable toxicities due to overexposure to the drug. We present two cases of
      advanced GIST patients in whom we managed imatinib-related toxicities through
      dose modifications guided by imatinib plasma level monitoring. Imatinib blood
      level testing may be a promising approach for fine-tuning imatinib dosage for
      better tolerability and optimal clinical outcomes in patients with advanced GIST.

PMID- 23960457
TI  - Intramedullary spinal cord metastasis in renal cell carcinoma: a case report of
      the surgical experience.
AB  - Intramedullary spinal cord metastasis (ISCM) from renal cell carcinoma (RCC) is
      rare manifestation and most of them are treated by adjuvant treatment modalities
      like radiotherapy. Despite the radio-resistance of RCC itself, focal radiotherapy
      has been preferred as the first-line treatment modality of ISCM from RCC and only
      a few cases underwent surgical treatment. We describe a case of ISCM from RCC,
      which underwent surgical excision and pathologically confirmed. A 44-yr-old man
      was presented with rapid deterioration of motor weakness during focal
      radiotherapy for ISCM from RCC. After the surgery for removal of the tumor mass
      and spinal cord decompression, his motor power was dramatically improved to
      ambulate by himself. We report the first published Korean case of ISCM from RCC
      confirmed pathologically and describe our surgical experience and his clinical
      characteristics. 

PMID- 23960458
TI  - Therapeutic hypothermia following emergent coronary artery bypass grafting after
      failed percutaneous coronary intervention in a comatose post-cardiac arrest
      patient.
AB  - We report the case of 60-yr-old female in which therapeutic hypothermia (TH) was
      successfully induced maintaining the target temperature of 34C for 12 hr despite
      a risk of hypothermia-induced coagulation abnormalities following an emergent
      coronary artery bypass grafting (CABG) due to failed percutaneous coronary
      intervention, who suffered a cardiac arrest. Emergent CABG may be a relative
      contraindication for TH in post-cardiac arrest patients because hypothermia may
      increase the risk of infection and bleeding. However, the possibility of an
      improved neurologic outcome outweighs the risk of bleeding, although major
      surgery may be a relative contraindication for TH. 

PMID- 23960460
TI  - The effect of aspirin on bleeding after extraction of teeth.
AB  - Acetylsalicylic acid (ASA) generically known as aspirin is used clinically as an
      analgesic, antipyretic, anti-inflammatory and as a medication to prevent platelet
      aggregation. Many studies have investigated bleeding associated with ASA.
      OBJECTIVE: The aim of this study was to determine if ASA was associated with
      bleeding after dental extraction. PATIENTS AND METHODS: One hundred and eighty
      nine subjects were divided into four groups. Group 1A subjects who received ASA,
      underwent simple extraction. Group 1B subjects who received ASA, underwent
      surgical extraction. Group 2A subjects who did not receive ASA, underwent simple
      extraction which served as control group. Group 2B subjects who did not receive
      ASA, underwent surgical extraction which also served as control group. RESULTS:
      The results showed that Group 1B was the only group which showed bleeding after
      24 h. All groups had similar results after 48 h and 5 days post-operatively.
      CONCLUSION: The study concluded that subjects who received 81 mg ASA daily could
      undergo dental extraction without bleeding risks.

PMID- 23960461
TI  - Attitudes of Saudi parents toward separation from their children during dental
      treatment.
AB  - OBJECTIVE: The purpose of this study was to investigate the attitudes of Saudi
      parents to being separated or not separated from their children in the dental
      office and to assess the factors affecting such attitudes. METHOD: Five hundred
      and five parents participated in the study by completing a questionnaire which
      included questions related to their sex, marital status, job, family income and
      reasons for seeking dental treatment for the child. Questions were also designed
      to determine the responses and attitudes of the parents regarding their presence
      in the dental clinic. RESULTS: Ninety-seven percent of the respondents preferred
      to stay with their children during dental treatment of their children. The main
      reason given by 83% of the parents was that the child would feel safe. More than
      72% of the parents reported that they would reduce their child's fear and comfort
      him/her during the dental treatment. CONCLUSIONS: From the parent's point of
      view, the most threatening dental procedure undergone by their children was
      dental anesthesia (87.7%) followed by the use of dental drills (55.4%). It can be
      concluded from the results that majority of Saudi parents studied preferred to
      stay with their children during treatment. Dentists should consider this when
      treating children.

PMID- 23960462
TI  - Effect of eugenol-based root canal sealers on retention of prefabricated metal
      posts luted with resin cement.
AB  - OBJECTIVE: This study evaluated the effect of two different eugenol-based root
      canal sealers on the retention of prefabricated metal posts luted with adhesive
      resin cement. MATERIALS AND METHODS: Thirty prefabricated ParaPosts randomly
      divided among three groups of 10 each were luted into extracted single-rooted
      teeth with adhesive resin cement. Two of the groups had been obturated with Gutta
      Percha and one of two eugenol-based root canal sealers (Endofil and Tubli-Seal),
      respectively. The third group was not obturated and served as the control. The
      forces required for dislodgment of posts from their prepared post spaces were
      recorded using a universal testing machine. Data were statistically analyzed
      using one-way ANOVA and Tukey's multiple range test was used to determine the
      mean differences. RESULTS: Endofil and Tubli-Seal groups demonstrated
      significantly reduced retention compared to the unobturated (control) group (P <
      0.05). CONCLUSION: Eugenol-based sealers significantly reduced the retention of
      prefabricated posts luted with adhesive resin cement.

PMID- 23960463
TI  - Granular cell tumour of tongue: A case report.
AB  - Granular cell tumour, also known as Abrikossoff tumour, is a relatively uncommon
      benign neoplasm, which is more commonly found in females in the 4th to 6th
      decades of life even though it can occur in all ages. It occurs in all areas of
      the body but about 45-65% of all lesions are reported in the head and neck
      region. Intraoral lesions represent about 70% of the granular cell tumours of the
      head and neck, and account for 1/3 of all cases affecting the whole body. Most of
      the intraoral lesions occur on the tongue, usually on the lateral aspect,
      followed by the buccal mucosa and hard palate. Although majority of granular cell
      tumours are benign, some are clinically aggressive and a few frankly malignant
      forms have been reported. Some benign lesions exhibit surface ulcerations and
      this clinical appearance, combined with the overlying pseudoepitheliomatous
      hyperplasia, seen histologically, may lead to misdiagnosis of malignancy if
      adequate biopsy material was not taken. A case of granular cell tumour which
      occurred on the midline area of the dorsum of the posterior 1/3 of the tongue is
      reported in a 20-year-old female patient. It is interesting because the patient
      was younger than the average age of occurrence and the tumour occurred in a
      similar site to that of a lingual thyroid. 

PMID- 23960464
TI  - A new device for impression transfer for non-parallel endosseus implants.
AB  - The three-dimensional orientation of dental implant is transferred to a model by
      means of transfer device and impression material. If more than one implant is
      inserted and fixtures are not perfectly parallel, the impression may become
      distorted when removed from the mouth. In this case, a transfer that can be
      disengaged from the internal implant-abutment connection and removed together
      with the tray could be useful. An impression transfer device composed of a proper
      transfer, an inner hexagon and a central screw is described. When the central
      screw and the hexagon are removed, the proper transfer is free to move
      horizontally and the tray can be removed from the mouth without distortion of the
      impression material. 

PMID- 23960466
TI  - The use of a single titanium microplate in displaced pediatric parasymphysial
      mandibular fractures.
AB  - OBJECTIVE: The objective of this study was to evaluate the use of one titanium
      microplate in the fixation of displaced pediatric parasymphysial mandibular
      fractures. MATERIALS AND METHODS: The study was conducted on 7 children in the
      mixed dentition stage with displaced parasymphysial fracture. Patients' age
      ranged between 5 years 9 months and 8 years 4 months with an average of 7 years 1
      month. Fractured bone segments were exposed, reduced and then fixed using 1.5
      linear microplates at the inferior border of the mandible using monocortical
      screws, with 1.5 mm in diameter and 5 mm in length. Stainless steel wire was used
      as a tension band by ligating the teeth around the fracture line. Patients were
      followed up for occlusion and stability clinically and radiographically
      (panoramic X-ray and CT). RESULTS: According to clinical and radiographic post
      operative follow-up, none of the patients showed displacement of the fixed bony
      segments. CONCLUSION: The present study concluded that using one microplate with
      1.5 monocortical microscrews and dental tension band by a stainless steel wire
      could be adequate for fixing displaced pediatric parasymphysial mandibular
      fractures. This technique has the following advantages: decreases the amount of
      titanium used, decreases the risk of injury of the roots and teeth buds, and
      decreases the cost and time of surgery.

PMID- 23960465
TI  - Surgical management of gingival recession: A clinical update.
AB  - Gingival recession is defined as the apical migration of the junctional
      epithelium with exposure of root surfaces. It is a common condition seen in both
      dentally aware populations and those with limited access to dental care. The
      etiology of the condition is multifactorial but is commonly associated with
      underlying alveolar morphology, tooth brushing, mechanical trauma and periodontal
      disease. Given the high rate of gingival recession defects among the general
      population, it is imperative that dental practitioners have an understanding of
      the etiology, complications and the management of the condition. The following
      review describes the surgical techniques to treat gingival recession. 

PMID- 23960467
TI  - Women in dentistry: A perspective on major universities in Saudi Arabia. Part 2:
      Analysis and statistical data.
AB  - PURPOSE AND SIGNIFICANCE: THE PURPOSES OF THIS STUDY WERE TO: (1) report the
      number of female graduates from the two oldest dental schools in Saudi Arabia;
      (2) compare the number of male and female graduates per year from these two major
      schools; and (3) compare these numbers of female dental graduates to those in the
      United States for the most recent year available, 2007. METHODS: This study was
      conducted using a descriptive non-experimental design. The study sample was the
      number of dental school graduates from the two major dental schools in Saudi
      Arabia. RESULTS: There were 1621 graduates of the College of Dentistry of King
      Saud University (KSU) since its inception up to 2007 of which 853 graduates were
      males and 768 were females, respectively. The total number of graduates from the
      Faculty of Dentistry of King Abdulaziz University (KAU) since its inception up
      till 2007 was 628 of which 264 were males and 364 were females. There was no
      statistically significant difference between the total number of male and female
      dental school graduates, although there was a significant difference between KSU
      and KAU dental schools. The proportion of female graduates from the two major
      Saudi dental schools was just over 50 % in 2007, which is slightly higher than
      the 45% female graduates from dental schools in the United States and Puerto
      Rico. CONCLUSIONS: Females currently comprise approximately half of the enrolled
      dental students at the KSU and KAU, a percentage slightly greater than that in
      the United States. The substantial enrollments suggested that women in Saudi
      Arabia consider dentistry to be an excellent career choice.

PMID- 23960468
TI  - Effect of surface treatment on the micro-shear bond strength to zirconia.
AB  - The constant quest for finding the ultimate esthetic dental restorative material
      has led to numerous alternatives. These materials, in addition to possessing
      optical properties simulating natural teeth, should also have physical properties
      that can withstand the harsh oral environment. Due to their greater toughness,
      zirconium oxide materials have been used as a core material for all-ceramic
      restorations. OBJECTIVE: The objective of this study was to evaluate the resin
      composite micro-shear bond strength to zirconia using different techniques of
      surface treatment. MATERIALS AND METHODS: Fully sintered zirconia (LAVA, 3M-ESPE,
      Seefeld, Germany) discs were used in combination with resin-composite (Filtek
      Supreme, 3M-ESPE, Seefeld, Germany) discs and divided into four groups of surface
      treatments. The micro-shear bond strength was measured by applying an axial load
      on the bonded interface until failure occurred. Failure load (N) was determined
      and the samples were examined under a SEM and the failure type was identified.
      One-way analysis of variance (ANOVA) was used to analyze the data with the level
      of significance alpha = 0.05. RESULTS: Data analysis revealed significant
      difference between the different tested surface treatments with the group using
      sandblasting and coated with an experimental primer showing the highest failure
      load and a cohesive fracture pattern. CONCLUSION: Within the limitations of this
      in vitro study the use of an experimental primer achieved a better bond strength
      in combination with air-abrasion particles.

PMID- 23960469
TI  - In vitro cariostatic effects of various iron supplements on the initiation of
      dental caries.
AB  - Previous animal and laboratory studies have shown the possible cariostatic effect
      of iron. The purpose of this study was to in vitro study the effect of different
      concentrations of four iron supplements on the initiation of dental caries.
      MATERIALS AND METHODS: Four products of iron supplements were used namely fre-in
      sol, ferotonic, feromin and ferose. Two hundred extracted teeth were distributed
      randomly into 10 groups. Eight groups were from the four iron products in two
      concentrations (100% and 50%) in addition to the positive and negative control
      groups. Mutans streptococci bacteria (6715) grown in Todd Hewitt Broth were used.
      Assessment of decalcification and cavitation was done daily for 60 days. RESULTS:
      It showed that different iron - supplement products play cariostatic effect in
      the initiation of the dental caries. With the exception of 100% and 50% ferose,
      both 100% and 50% concentrations of all supplements have cariostatic effect. The
      mean dates for decalcification varied with lowest for the positive control (12.2
      days) and the highest was for 50% feromin. Cavitation was seen in the positive
      control and 100% ferose groups with mean on the first day of cavitation of 57
      days. CONCLUSION: It was concluded that iron may have cariostatic effect on the
      in vitro development of dental caries in human teeth.

PMID- 23960470
TI  - Stability of the mandible after bilateral sagittal split osteotomy: Comparison
      between positioning screws and plate.
AB  - Relapse is one of the complications of orthognathic surgery. In this study, we
      compared the stability of mandibular bilateral sagittal split osteotomy by using
      two different methods of fixation. In Group 1, eight patients with prognathic
      mandible underwent BSSO and set back average of 6.0 mm. The method of fixation
      was positioning screws. In Group 2, eight patients with prognathic mandible
      underwent BSSO and set back average of 6.0 mm. The method of fixation was plate
      and monocortical screws. In Group 3, eight patients with retrognathic mandible
      underwent BSSO and advancement average of 6.0 mm. The method of fixation was
      positioning screws. In Group 4, eight patients with retrognathic mandible
      underwent BSSO and advancement average of 6.0 mm. The method of fixation was
      plate and monocortical screws. The results showed in terms of advancement that
      there was no significant difference between the groups after one year. However,
      in terms of set back, this study showed significant difference. 

PMID- 23960471
TI  - The use of povidone-iodine and hydrogen peroxide mixture as an adjunct to non
      surgical treatment of slight to moderate chronic periodontitis.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical effects of the
      adjunctive use of povidone-iodine with or without hydrogen peroxide as coolant
      and disinfectant during ultrasonic scaling and root planing in the treatment of
      chronic periodontitis. MATERIALS AND METHODS: Sixteen patients initially
      participated in the study. Thirteen patients (8 males and 5 females) completed
      the 3-month follow-up period. Their mean (+/-SD) age was 42.92 +/- 7.55 years. In
      each experimental subject, the mouth was split into four quadrants. A randomly
      selected quadrant was chosen to receive one of the three treatment group
      modalities which were: Group 1 - ultrasonic scaling and root planing plus
      irrigation with 1% povidone-iodine and 3.0% hydrogen peroxide mixture; Group 2 -
      ultrasonic scaling and root planing plus irrigation with 1% povidone-iodine;
      Group 3 - ultrasonic scaling and root planing plus irrigation with normal saline.
      The fourth quadrant served as a control group. RESULTS: At the 3-month
      evaluation, there was no significant difference between the three treatment
      groups in terms of probing depth reduction, clinical attachment gain, gingival
      recession increase, reduction in the bleeding upon probing or plaque score
      reduction (P > 0.05). However, the three treatment groups had statistically
      significant higher mean reduction in the probing depth, gain in the clinical
      attachment level and reduction in the bleeding upon probing than the control
      group (P < 0.05). CONCLUSION: There were no added benefits of using a mixture of
      povidone-iodine and hydrogen peroxide or povidone-iodine as disinfectants during
      ultrasonic scaling and root planing in the treatment of chronic periodontitis.

PMID- 23960472
TI  - Predoctoral dental implant education at King Abdulaziz University.
AB  - OBJECTIVE: In June 2008, a survey of freshly graduated dental students of King
      Abdulaziz University Jeddah was conducted to evaluate the extent of their
      exposure to oral implantology and their knowledge of some basic principles of
      dental implant treatment. MATERIALS AND METHODS: Multiple-choice questionnaires
      were given to the fresh graduate dental students of King Abdulaziz University
      Jeddah to answer. Sixty-six students responded out of 86, yielding a response
      rate of 76.7%. RESULTS: Majority of the students (78.8%) thought that they did
      not have enough lectures about dental implants and all of them thought that they
      did not have enough training in dental implant. Most of the students were not
      familiar with different dental implant systems (61.1%), designs (60.6%) or sizes
      (74.2%). Majority of the students were lacking the knowledge about basic
      principles of dental implant treatment. At King Abdulaziz University, Faculty of
      Dentistry, implant dentistry is taught to the students in the form of implant
      related lectures incorporated into their periodontic, oral surgery and
      prosthodontic courses with one or two lectures given on dental implant in each
      course. CONCLUSION: There is an urgent need to develop a well-structured implant
      course that includes didactic, laboratory, preclinical and clinical components at
      the undergraduate curriculum of King Abdulaziz University Faculty of Dentistry.

PMID- 23960473
TI  - Corticotomy facilitated orthodontics: Review of a technique.
AB  - Corticotomy found to be effective in accelerating orthodontic treatment. The most
      important factors in the success of this technique is proper case selection and
      careful surgical and orthodontic treatment. Corticotomy facilitated orthodontics
      advocated for comprehensive fixed orthodontic appliances in conjunction with full
      thickness flaps and labial and lingual corticotomies around teeth to be moved.
      Bone graft should be applied directly over the bone cuts and the flap sutured in
      place. Tooth movement should be initiated two weeks after the surgery, and every
      two weeks thereafter by activation of the orthodontic appliance. Orthodontic
      treatment time with this technique will be reduced to one-third the time of
      conventional orthodontics. Alveolar augmentation of labial and lingual cortical
      plates were used in an effort to enhance and strengthen the periodontium,
      reasoning that the addition of bone to alveolar housing of the teeth, using
      modern bone grafting techniques, ensures root coverage as the dental arch
      expanded. Corticotomy facilitated orthodontics is promising procedure but only
      few cases were reported in the literature. Controlled clinical and histological
      studies are needed to understand the biology of tooth movement with this
      procedure, the effect on teeth and bone, post-retention stability, measuring the
      volume of mature bone formation, and determining the status of the periodontium
      and roots after treatment. 

PMID- 23960474
TI  - The effect of mechanical and chemical polishing techniques on the surface
      roughness of denture base acrylic resins.
AB  - Smooth polished surface of dental prostheses is important to prevent bacterial
      colonization and plaque accumulation. The acrylic base of prosthodontic
      appliances needs to be adjusted by grinding which often alters the surface of the
      denture base. It is therefore important to know how different polishing
      techniques affect surface roughness of acrylic resin. OBJECTIVE: The aim of this
      study was to evaluate the effect of mechanical polishing (MP) and chemical
      polishing (CP) on the surface roughness of heat cured (HC) and auto cured (AC)
      denture base acrylic resins. MATERIALS AND METHODS: Sixty acrylic resin specimens
      (30 * 15 * 3 mm) were made for each of the two types of acrylic resins. Thirty HC
      specimens received mechanical conventional lathe polishing using cone with pumice
      slurry and soft brush with chalk powder. The other thirty HC specimens received
      chemical polishing by immersing in methyl-methacrylate monomer heated to 75 
      degrees C +/- 1  degrees C for 10 s. The sixty AC specimens received mechanical
      and chemical polishing in the same manner. Surface roughness was measured using
      surface analyzing instrument in microns. The data were statistically analyzed by
      two-way analysis of variance (ANOVA) followed by post hoc Tukey's test (alpha =
      0.05). RESULTS: THE SURFACE ROUGHNESS MEAN IN MICRONS IN ORDER OF DECREASING
      VALUES WERE: CP-HC: 1.4132 MUm; CP-AC: 1.3494 MUm; MP-AC: 0.7364 MUm and MP-HC:
      0.6333 MUm. Two-way ANOVA revealed that the MP-HC was significantly different
      from CP-HC and CP-AC (P < 0.05). The MP-AC is also significantly different from
      CP-HC and CP-AC (P < 0.05). There was no significant difference between MP and CP
      of HC and AC acrylic resin groups. CONCLUSION: It can be concluded that MP
      produced significantly smoother surfaces than CP. The surface roughness obtained
      by MP was not influenced by acrylic resin type where as this was not true for CP.

PMID- 23960475
TI  - Factors affecting utilization of dental health services and satisfaction among
      adolescent females in Riyadh City.
AB  - OBJECTIVES: This study was conducted to determine factors affecting utilization
      of dental health services among intermediate female school students in Riyadh. In
      addition to assessing their satisfaction with the dental care received during the
      last dental visit. SUBJECTS AND METHODS: Self-administered questionnaires were
      distributed among students attending eight public and four private schools. These
      schools were selected randomly to represent the four different administrative
      zones in Riyadh. RESULTS: Of 600 questionnaires distributed, 531 were complete
      and suitable for analysis. Nearly three quarters of the students visited the
      dentist more than once during the last 2 years. A bout 75% had their treatment in
      private dental clinics and 63% made their visits for routine treatment. The
      quality of dental care was found to be the most encouraging factor for
      utilization of dental services, whereas, far geographic location of the dental
      clinics was the most discouraging factor. For those who received treatment in the
      government clinics, the most discouraging factor was post operative complications
      (P < 0.0001), while the most encouraging factor was the availability of friendly
      staff (P < 0.0001). The high cost of dental care was the most discouraging factor
      for utilizing the dental services for those who visited private clinics (P <
      0.0001), while the high quality of dental care was the most encouraging factor (P
      < 0.009). Students who made their visits because of pain highly considered modern
      clinics and those recommended by friends as highly encouraging factors (P <
      0.002), while they considered the high cost of dental care as discouraging factor
      for using dental services (P < 0.038). Students who visited the dentist for
      routine treatment gave the quality of dental care as encouraging for the use of
      dental clinics (P < 0.0001). Satisfaction with dental care was found to be
      significantly associated with high quality of dental care, convenient
      appointment, friendly staff, modern dental clinics and clinics recommended by
      friends. CONCLUSION: Quality of dental care, reasonable fees for dental services
      and close location of dental clinics to students' homes are encouraging factors
      for utilization of dental services.

PMID- 23960477
TI  - The applicability of a non-anatomical soft and hard tissue centroid line (S&H
      centroid) in cephalometrics.
AB  - The applicability of a newly introduced non-anatomical soft and hard tissue
      cephalometric centroid line (S&H centroid) was investigated. The "S&H centroid"
      line established from 12" * 14" lateral cephalometric radiographs of 57 selected
      adults was used as a base to create a new cephalometric reference line "Centroid
      Nasion". The reliability and the use of the newly created "Centroid-Nasion" as a
      reference line was tested against the conventional "Sella-Nasion" cephalometric
      reference line to evaluate the sagittal and vertical maxillary and mandibular
      relationship. Pearson's correlation coefficient, one way ANOVA, and Tukey
      multiple comparison post Hoc statistical tests were used. The digitization
      technique was reliable. The "Centroid-Nasion" cephalometric reference line
      created by utilizing the "S&H centroid" line, was found to be as useful as the
      conventional "Sella-Nasion" cephalometric plane in establishing and
      differentiating between sagittal and vertical intermaxillary relationships. 

PMID- 23960476
TI  - Differential expression of c-kit and CD43 in histological subtypes of adenoid
      cystic carcinoma of salivary gland.
AB  - Adenoid cystic carcinoma (ACC) of the salivary gland is characterized by a
      prolonged but inevitably unfavorable clinical course. Recent studies have
      suggested that the transmembrane tyrosine kinase receptor, c-kit proto-oncogene
      is involved in ACC pathogenesis. CD43 is a sialoglycoprotein that is typically
      expressed by hematopoietic cells and their derivative neoplasms, although
      positivity in epithelial tumors has only been recognized recently. OBJECTIVE: The
      aim of this study was to evaluate c-kit and CD43 immunoreactivity in ACCs and to
      compare the extent of their expression in various histologically defined
      subgroups of ACC, and their probable involvement in ACC pathogenesis. STUDY
      DESIGN: Formalin-fixed paraffin-embedded sections from 35 ACCs were immunostained
      for c-kit and CD43 using monoclonal antibodies. RESULTS: Cytoplasmic and
      membranous c-kit immunoreactivity was detected in 25/35 ACCs (71.4%) with strong
      immunostaining observed in solid pattern of ACC. Cytoplasmic and membranous CD43
      immunoreactivity was detected in 18/35 (51.4%) of ACCs with strong immunostaining
      seen in the cribriform pattern. CONCLUSIONS: These results suggested that c-kit
      could be used as a prognostic marker for ACC and specific c-kit tyrosine kinase
      inhibitors such as imatinib, might be used in future therapeutic approaches
      against subgroups of ACC. CD43 appears to be preferentially expressed in salivary
      gland ACCs. Its expression decreased with cellular dedifferentiation and there
      was an inverse relationship between immunoexpression of c-kit and CD43 among ACC
      of salivary gland.

PMID- 23960478
TI  - Anterior alveolar dimensions among different classifications of sagittal jaw
      relationship in Saudi subjects.
AB  - Sound orthodontic movement of anterior teeth is delineated by the biological
      dimensions of the anterior alveolus. OBJECTIVE: To establish and compare the
      anterior alveolar dimensions among normal and abnormal sagittal maxillomandibular
      relationships in a Saudi sample. MATERIALS AND METHODS: The lateral cephalometric
      radiographs of 81 Saudi subjects (42 males and 39 females) were used to determine
      the anteroposterior and vertical dimensions of the anterior alveolus in Class I
      (N = 30), Class II (N = 24), and Class III (N = 27) cases. The anterior alveolar
      dimensions were then compared among males and females belonging to the same
      sagittal classification and between the different sagittal classifications of the
      same gender. RESULTS: Significant differences (P < 0.05) in the anterior alveolar
      dimensions between males and females were demonstrated for the same sagittal jaw
      classification. Also, significant differences (P < 0.05) were detected between
      the anterior alveolar dimensions among the different sagittal maxillomandibular
      classifications of the same gender. CONCLUSION: Both the gender and the sagittal
      maxillomandibular relationship can affect the anteroposterior and vertical
      dimensions of the anterior alveolus.

PMID- 23960479
TI  - Attitudes of Saudi mothers towards prolonged non-nutritive sucking habits in
      children.
AB  - OBJECTIVES: The purpose of the present study was to evaluate Saudi mothers'
      attitude towards non-nutritive sucking habits by their children and report the
      methods they used to stop these habits. METHODS: Across-sectional study involved
      181 mothers of preschool children currently engaged in non-nutritive sucking
      habits (digit and pacifier) were studied. The information was obtained from a
      self-administered questionnaire completed by the mothers. RESULTS: The majority
      of mothers (69.1%) were from high socio-economic families, (77%) had university
      or higher education and more than half of them (58.6%) were employed. About 75%
      of the children were pacifier users, and 25% of them habitually sucked their
      digits. Nearly half of the mothers (43.5%) thought that the reason of acquiring
      the habit was because their children cried a lot at night. The majority of
      studied mothers (88.7%) considered sucking a harmful habit to their children'
      teeth, and 69.1% never accepted the sucking habit. High percentage (80.8%) of
      mothers tried to intervene with these habits and 61.0% of them tried their
      intervention when children were one year old or less. Most proposed reasons for
      mothers' intervention with sucking habits were their concerns that the habit
      might continue until the child become older (53.3%) followed by their concern
      that the habit might affect their children's permanent teeth (45.3%). The methods
      used by mothers were mostly non-invasive procedures which included restricting
      the use of pacifier to specific times in the day (63.0%), followed by
      reinforcement of positive behaviors and using rewards (26.0%). None of the
      mothers sought advice from pediatrician while only one mother (0.6%) consulted a
      dentist about sucking habits. CONCLUSION: This study shows that Saudi mothers are
      concerned about sucking habits and recognized the harmful effect on their
      children. These mothers, however, are in great need for education about ways of
      preventing the habits in the first place as well as professional advice and help
      in treatment cessation of already established habits.

PMID- 23960480
TI  - Survey of perceived stress-inducing problems among dental students, Saudi Arabia.
AB  - OBJECTIVE: This study was conducted to assess the problems related to stress
      encountered by Saudi dental students. METHODS: One thousand and thirty
      questionnaires were distributed in four dental schools to all students from 2nd
      year level up to the internship level. The questionnaire contained 66 items
      organized into four categories: personal and administrative, theoretical,
      preclinical and clinical. The relationship between the demographic variables and
      students' academic performance with the investigated items was also assessed.
      RESULTS: The response rate was 53%. Saudi dental students showed high levels of
      perceived stress. The clinical training issues imposed the highest level of
      stress on the students. Some significant relationships between the investigated
      variables and the level of the perceived stress were found. CONCLUSIONS: Female
      students had higher mean overall problem scores compared to male students, and
      second-year students showed lower perceived problems compared to other students.

PMID- 23960481
TI  - A study of HER-2/neu expression and silver binding nucleolar organizer regions
      (Ag NORs) in perilesional normal salivary gland tissue.
AB  - Salivary gland neoplasms comprise phenotypically and biologically diverse lesions
      of uncertain histogenesis. OBJECTIVES: The present study was carried out to
      assess the immunohistochemical expression of HER-2/neu protein and of silver
      binding nucleolar organizer regions in normal salivary tissue. MATERIALS AND
      METHODS: Twenty paraffin blocks of salivary tumors containing surrounding normal
      salivary tissue were used in the study. One section was processed to investigate
      HER-2/neu protein expression and another section was stained to assess the mean
      Ag NOR counts in normal salivary tissue. RESULTS: Only two cases of the studied
      normal salivary tissue showed HER-2/neu expression (10%), which was expressed
      only in ductal cells with 4.2 +/- 2.1 mean number of reactive cells per five high
      power fields (HPFs). Statistically significant (P = 0.01) higher mean Ag NOR
      counts in ductal (2 +/- 0.83) than in acinar cells (1.2 +/- 0.01) of normal
      salivary tissue were found. CONCLUSION: It was concluded from the data of the
      present study that ductal cells of normal salivary tissue are a proliferative
      pool and an oncogenic target which plays an important role in the histogenesis of
      salivary gland tumors.

PMID- 23960482
TI  - "Booby-Trap" - Dental implants at bay.

PMID- 23960483
TI  - Congenital double upper lip: A case report and review of the literature.
AB  - Congenital double lip is a rare developmental anomaly which usually involves the
      upper lip more than the lower lip. It may occur in isolation or as a part of
      Ascher's syndrome. Sometimes upper and lower double lips occur simultaneously.
      The occurrence of double lip may result in facial deformity especially when the
      patient attempts to talk, smile or even show the teeth. It may also interfere
      with speech or mastication. Although surgery may be undertaken to facilitate
      speech and mastication, the majority of cases are operated for cosmetic reasons.
      A case of congenital double upper lip, which was surgically treated after
      orthodontic treatment, for cosmetic reasons, is reported. The different surgical
      approaches to the management of double upper lip are reviewed with a note on
      timing of surgery in patients who have concurrent orthodontic or prosthodontic
      problems. Although the majority of cases of double lip are treated by Plastic
      Surgeons and Oral and Maxillofacial Surgeons, it is important to make dentists
      aware of this condition since they may be the first clinicians to encounter
      patients with this abnormality. 

PMID- 23960484
TI  - Bi-axial flexural strength of dual-polymerizing agents cemented to human dentin
      after photo-activation with different light-curing systems.
AB  - OBJECTIVES: This study aimed to assess the bi-axial flexural strength of two dual
      polymerizing resin luting agents cemented to human dentin when photo-activated
      with different light-curing units. MATERIALS AND METHODS: Two dual-cured resin
      cements: choice (CH) and Variolink II (VL) were tested. Hybrid composite resin (Z
      250) discs (12 * 1.5 mm) were fabricated. Three types of light-curing units were
      used halogen-curing unit (QTH), light-emitting diode (LED) and plasma arc (PAC).
      Sixty dentin discs of 0.5 mm thickness were prepared from extracted human teeth.
      A circular mold (2.5 mm in height and 12 mm diameter) was utilized to create
      supporting structure for dentin, resin cement complex. The resin luting cement
      (0.5 mm) was placed on the previously prepared dentin discs and covered with the
      prefabricated composite discs. Photo-activation of cements was performed for 40 s
      with QTH and LED units and for 3 s with PAC. The specimens were divided into 12
      groups (20 specimens for each light source). Six groups were kept in distilled
      water for 24 h and the rest were stored for 6 weeks. Bi-axial flexural strength
      was determined using Instron machine. The data was analyzed using two-way ANOVA
      and Tukey test for comparison. RESULTS: The findings indicated that the bi-axial
      flexural strength values for both cements CH and VL were higher for 24 h over 6
      weeks but not statistically significant when cured with QTH. Meanwhile, when LED
      light was used for photo-activation the cements, the flexural strength values
      reported were statistically higher of 24 h over 6 weeks storage at P = 0.4(E-6)
      However, PAC light did not record any statistically significant difference
      between two duration for the CH cement although when used for polymerization of
      VL the reported value for 6 weeks were statistically significantly higher value
      than 24 h duration at P = 0.002. CONCLUSION: When high immediate flexural
      strength is preferred in clinical situation photo-activation the cements with LED
      reported the greatest value.

PMID- 23960485
TI  - A survey of root canal treatment of molar teeth by general dental practitioners
      in private practice in Saudi Arabia.
AB  - The purpose of this study was to evaluate the practice and depth of knowledge of
      root canal treatment by general dental practitioners working in private dental
      centers in different cities within the Kingdom of Saudi Arabia. A questionnaire
      was distributed to 400 general dental practitioners. Completed questionnaires
      were analyzed in term of simple summary statistics. A total of 252 (63%)
      practitioners responded. The majority of the respondents were Syrians (59%) and
      Egyptians (32%). Ninety-one per cent of the respondents indicated that they
      performed root canal treatment. Amongst those who carried out root canal
      treatment, only seven practitioners (3%) used rubber dam for isolation. More than
      half of the respondents (55%) used saline to irrigate canals during treatment.
      Forty-six per cent of practitioners used formocresol as an inter appointment
      medicament. The standardized and step-back preparation techniques were the method
      of choice for the majority of the respondents (91%). Ninety-seven per cent of the
      practitioners used stainless steel hand instruments to prepare root canals and
      the majority (92%) used gutta-percha for obturation. Seventy-four per cent of the
      respondent used cold lateral condensation. The average number of radiographs
      routinely taken for root canal treatment was four. Ninety-three per cent
      indicated that they usually completed a root canal treatment of molar teeth in
      three or more visits. Eighty-eight per cent of the practitioners preferred
      waiting for 1 or 2 weeks to restore the teeth permanently. Results of this study
      confirm that many general dental practitioners are not following quality
      guidelines for endodontic treatment. 

PMID- 23960486
TI  - The comparison of MTA, Geristore(r) and Amalgam with or without Bioglass as a
      matrix in sealing the furcal perforations (in vitro study).
AB  - AIM: The objective of this in vitro was to assess the sealing ability of MTA,
      Geristore(r), and amalgam with and without Bioglass as a matrix used to repair
      furcation perforations in mandibular molars by using dye penetration. MATERIALS
      AND METHODS: One hundred mandibular molars were randomly divided into six
      experimental groups. Five teeth with perforation were used as positive control
      while five teeth without perforation were used as negative control group. Furcal
      perforations were made in the teeth. Perforations were repaired with amalgam in
      group 1, amalgam and Bioglass in group 2, MTA in group 3, MTA and Bioglass in
      group 4, Geristore(r) in group 5, and Geristore(r) and Bioglass in group 6. All
      repairing materials were allowed to set for 72 h. Leakage at the repaired sites
      was then evaluated using dye penetration and clearing technique under
      stereomicroscope. RESULTS: The perforations repaired with MTA and Geristore(r)
      leaked significantly less than amalgam (p = 0.000). Bioglass reduced sealing
      ability of MTA and Geristore(r) significantly (p = 0.000, p = 0.019), while
      reduced the sealing ability of amalgam insignificantly (p = 0.78). CONCLUSION:
      MTA and Geristore(r) have shown acceptable sealing ability in furcal perforation
      in comparison to amalgam while Bioglass as a matrix beneath them has reduced
      their sealing ability.

PMID- 23960487
TI  - Usage of removable partial dentures in Saudi male patients after 1 year telephone
      interview.
AB  - OBJECTIVE: The success of removable partial dentures (RPDs) is partly dependent
      on patients' acceptance and compliance in using them. The purpose of this study
      was to describe the usage of removable partial dentures (RPDs) by patients 1 year
      after insertion and to evaluate the factors that influence their denture usage.
      METHODS: Forty-seven patients who received 75 new RPDs at the undergraduate
      clinic of College of Dentistry, King Saud University, were contacted by telephone
      1 year later for an interview. The questions covered denture usage, patient's
      satisfaction and reasons for non-use. RESULTS: Results showed that 36% of
      patients discarded or occasionally used their RPDs. There was no significant
      association between denture usage and RPD experience, location or Kennedy
      classification. A significantly more RPD rejection was found when it was opposed
      by natural teeth or complete denture. The most quoted reason for RPD rejection
      was pain and discomfort. CONCLUSION: Despite the short follow-up period, RPDs
      were poorly accepted by patients treated by undergraduate students.

PMID- 23960488
TI  - Levels of gingival crevicular metalloproteinases-8 and -9 in periodontitis.
AB  - Matrix metalloproteinases (MMPs), the key enzymes responsible for matrix
      degradation, are derived from polymorphonuclear leukocytes during the early
      stages of periodontitis. The aim of this study was planned to determine the
      levels of GCF (gingival crevicular fluid) matrix metalloproteinase-8 (MMP-8) and
      metalloproteinase-9 (MMP-9) patients with periodontitis and in healthy controls.
      Levels of crevicular MMP-8 and -9 were determined by ELISA in subjects with
      healthy without any periodontal disease (n = 10) and periodontitis (n = 10).
      Significantly higher crevicular MMP-8 and -9 were observed in cases of
      periodontitis compared to healthy adults. Crevicular MMP-8 and -9 may serve as
      biomarkers of periodontal disease and aid in early detection of periodontitis. 

PMID- 23960489
TI  - Orthognathic surgical norms for a sample of Saudi adults: Hard tissue
      measurements.
AB  - OBJECTIVE: The aim of the study is to establish hard tissue cephalometric norms
      for orthognathic surgery for a sample of Saudi adults. MATERIALS AND METHODS:
      Sixty-two lateral cephalometric radiographs for 31 females and 31 males, age
      range of 22-24 years, were analysed. The mean values of the hard and dental
      measurements were compared with those of European-American adults using Burstone
      analysis, as well as comparison between Saudi males and females. RESULTS: Saudi
      males had an increased cranial base length, the mandible lied more posterior to
      maxilla, increased mandibular plane angle and backward rotation of the mandible
      with less prominent chin, shorter maxillary length, and also less proclination of
      lower incisors compared to those of European Americans. Saudi females had similar
      cranial base length and shorter maxillary length than European Americans. In both
      gender; lower anterior and posterior dental heights were smaller when compared
      with the European-Americans' values. A significant difference between Saudi males
      and females was found. Saudi males showed longer cranial base length, larger
      vertical skeletal proportion, increased dental values, longer maxillary and
      mandibular length than the female group. CONCLUSION: This study may be useful in
      providing racially specific cephalometric norms for diagnosis and treatment
      planning for orthognathic surgery for a sample of Saudi adults.

PMID- 23960490
TI  - A foreign body in the floor of the mouth.
AB  - A case of unusual presentation of foreign body in the floor of mouth is reported.
      The patient presented with a history and clinical findings of sublingual ranula.
      Marsupialisation and sublingual sialadenectomy was planned. After
      marsupialisation, a foreign body (spray cover) was found between the lumen of the
      submandibular duct and the ranula. 

PMID- 23960491
TI  - Compound composite odontoma with unusual number of denticles - A rare entity.
AB  - Compound odontoma is stated to be a hamartomatous lesion rather than a true
      odontogenic tumour. It has an unknown etiology and often suspected when there are
      retained deciduous teeth in children. Early detection and surgical enucleation of
      the tumour is recommended to prevent impaction of unerupted teeth. In this index
      case, multiple denticles or rudimentary teeth, numbering 37 were enucleated from
      the maxillary anterior region of a 17-year old male, which makes this case
      unusual. Evidence of concrescence, fusion and dilaceration were observed in the
      denticles enucleated, the size of which varied from 4 mm to 12.5 mm. 

PMID- 23960492
TI  - Engipore acts on human bone marrow stem cells.
AB  - OBJECTIVES: Porous HA scaffolds are promising materials for tissue engineering
      because they offer a tridimensional support and serve as template for cell
      proliferation and at last tissue formation. Engipore provide a natural 3D
      scaffold with organic fibrous material in bone. However, how this material alters
      osteoblast activity to promote bone formation is poorly understood. MATERIALS AND
      METHODS: To study how Engipore can induce osteoblast differentiation in
      mesenchymal stem cells, the expression levels of bone related genes and
      mesenchymal stem cells marker were analyzed. RESULTS: Engipore causes a
      significant induction of osteoblast transcriptional factors like SP7 and RUNX2
      and of the bone-related gene osteocalcin (BGLAP). The expression of CD105 was not
      significantly changed in stem cells treated with Engipore with respect to
      untreated cells, while SSP1 (osteopontin) was significantly down expressed thus
      reducing osteoclast activity. CONCLUSIONS: The obtained results can be relevant
      to better understand the molecular mechanism of bone regeneration.

PMID- 23960493
TI  - Immunohistochemical analysis of P53 protein in odontogenic cysts.
AB  - The p53 is a well-known tumor suppressor gene, the mutations of which are closely
      related to the decreased differentiation of cells. Findings of studies on
      immunohistochemical P53 expression in odontogenic cysts are controversial. The
      present study was carried-out to investigate the immunohistochemical expression
      of P53 protein in odontogenic cysts. Thirty paraffin blocks of diagnosed
      odontogenic cysts were processed to determine the immunohistochemical expression
      of P53 protein. Nine of the 11 odontogenic keratocysts (81.8%) expressed P53, one
      of three dentigerous cyst cases expressed P53, while none of the 16 radicular
      cysts expressed P53 protein. The findings of the present work supported the
      reclassification of OKC as keratocystic odontogenic tumor. 

PMID- 23960494
TI  - Shear bond strength of one-step self-etch adhesives with different co-solvent
      ingredients to dry or moist dentin.
AB  - OBJECTIVE: To evaluate the shear bond strength of one-step self-etch adhesives
      with different co-solvent ingredients to dry or moist dentin. MATERIALS AND
      METHODS: A total of 60 extracted teeth were used in this study, and were divided
      according to the adhesive systems and dentin conditions into 6 groups of 10 teeth
      each [Xeno III - dry dentin, Xeno III - moist dentin, Adper Prompot L-Pop - dry
      dentin, Adper Prompot L-Pop - moist dentin, iBond - dry dentin, and iBond - moist
      dentin]. Resin composite cylinder was built up on each specimen, and then
      thermocycled. A shear load was applied to the specimens using universal testing
      (Instron machine) at a cross-head speed of 0.5 mm/min until failure occurred.
      Data were statistically analyzed by one-way ANOVA and Bonferroni multiple
      comparison test at 95% confidence level. RESULTS AND CONCLUSION: BASED ON THE
      FINDINGS OF THIS STUDY: The highest mean shear bond strength to dry dentin was
      seen when Xeno III containing ethanol co-solvent ingredient was used. The highest
      mean shear bond strength to moist dentin was seen when iBond which contains
      acetone co-solvent ingredient was used. In the absence of a co-solvent ingredient
      in self-etch adhesive (Adper Prompot L-Pop), the mean shear bond strengths to dry
      and moist dentin were low with no significant difference between them.

PMID- 23960495
TI  - Dental patients' awareness and knowledge in using dental implants as an option in
      replacing missing teeth: A survey in Riyadh, Saudi Arabia.
AB  - AIM: The purpose of this survey was to assess the level, sources, and need for
      information about dental implants among a selected sample of dental patients in
      Riyadh, Saudi Arabia. MATERIALS AND METHODS: Patients' knowledge and awareness in
      using dental implants as an option in replacing missing teeth were evaluated
      through a standardized self- explanatory questionnaire distributed in two places
      in Riyadh: Military Hospital and College of Dentistry, King Saud University
      (Darraiyah campus). The questionnaires were handed to the patients during their
      regular dental visits. A total of 379 subjects were included in this survey.
      RESULTS: The results of this study indicate that 66.4% of the subjects knew about
      dental implants. The subjects' friends and their relatives were the main source
      of information about dental implants for 31.5% of the subjects, and dentists were
      the secondary source for 28.3% of the sample. About 82.4% of the subjects need
      more information about dental implants and 85.2% of them chose the dentist to be
      the desired source for such information, followed by the internet in 28.5% of the
      cases. Almost 74.4% of those surveyed did not know if their regular dentists use
      dental implants. High cost was the major factor in preventing patients from
      choosing implants in 86.5% of the cases while the long treatment time and fear of
      surgery was the factor in 71% and 68.6% of the subjects, respectively.
      CONCLUSION: The results of this survey showed an acceptable level of awareness
      about dental implants among a selected sample of dental patients in Riyadh. It
      also showed the need for providing more general and accurate information to the
      patients about this treatment modality.

PMID- 23960496
TI  - Fluoride content of bottled drinking waters available in Riyadh, Saudi Arabia.
AB  - AIMS: This study aimed to examine the fluoride concentration of commercially
      available bottled water products in Riyadh, Saudi Arabia, and to assess the
      accuracy of the labeling of fluoride concentration on the tested brands. METHODS:
      Fifteen randomly selected commercial brands of bottled water were obtained from
      supermarkets in Riyadh, Saudi Arabia. Three bottles of each brand were purchased,
      and fluoride content was measured using a combination fluoride-ion-selective
      electrode. The average reading for each brand was estimated and also compared
      with the fluoride content printed on the label. RESULTS: The mean (+/-SD)
      fluoride content of the 12 local bottled water samples was 0.79 (+/-0.09) mg/L
      with a range from 0.5 to 0.83 mg/L. The mean fluoride concentration of the three
      imported brands was 0.67 (+/-0.02) mg/L with a narrow range of fluoride content
      (0.65-0.69). All tested samples mention the fluoride content on the label except
      two imported brands. Five samples showed a significant difference between our
      evaluation and stated content of fluoride that ranged between +0.46 and -0.2
      mg/L. CONCLUSIONS: Bottled drinking waters available in Riyadh, Saudi Arabia
      contain differing concentration of fluoride, but within a safe range for use as a
      source of systemic fluoride. In addition, the manufactures' labeling of fluoride
      content may be inaccurate.

PMID- 23960497
TI  - Assessment of OsstellTM and Periotest(r) systems in measuring dental implant
      stability (in vitro study).
AB  - OBJECTIVES: The objectives of this in vitro study were to investigate the
      sensitivity and reliability of the OsstellTM systems (Resonance Frequency
      Analysis - RFA) compared to the Periotest(r) system in implant bone simulated
      conditions. Three conditions were simulated: (1) the direct fixture-bone contact
      and fibrous tissue fixture contact, (2) The different levels of horizontal bone
      loss, and (3) The hardening implant-bone interface. MATERIALS AND METHODS: Forty
      nine dental implant fixtures were placed in the center of acrylic cubes. In Part
      I seven fixtures were placed in direct contact with acrylic and another seven
      were placed in contact with polyvinyl siloxane impression material as soft
      interface. Part II: four sets of 0, 2, 4 and 6 mm horizontally exposed fixture
      samples were made (seven fixtures in each set). Part III: seven fixtures were
      placed in contact with a thin mix of autopolymerizing resin. The stability of
      these fixtures was measured using OsstellTM and Periotest(r) systems. RESULTS:
      The mean Periotest(r) value(PTV) and OsstellTM measurements showed a significant
      difference between the direct contact and soft interface (P < 0.001). These
      values also showed statistically significant difference between the different
      levels of horizontally exposed fixture groups (P < 0.001). The level of
      horizontal fixture exposure was strongly correlated with the PTVS (r = 0.967) and
      strongly negatively correlated with Implant Stability Quotient (r = -0.946). A
      strong correlation was found between the OsstellTM readings and the change in the
      stiffness of the autopolymerizing resin fixture interface group (r = 0.986).
      CONCLUSIONS: Both OsstellTM and Periotest(r) systems proved to be sensitive in
      measuring dental implant stability in hard and in soft interfaces. OsstellTM also
      proved to be sensitive in detecting changes in the fixture interface stiffness.
      OsstellTM system proved to be more reliable compared to Periotest(r) system in
      measuring dental implant stability in hard and in soft interfaces.

PMID- 23960498
TI  - Cephalometric characteristics of Class II division 1 malocclusion in a Saudi
      population living in the western region.
AB  - OBJECTIVE: To describe and analyze the cephalometric dento-skeletal
      characteristics associated with Angle's Class II, division 1 malocclusion in
      Saudi population living in the western region. MATERIALS AND METHODS: The
      material examined included 149 lateral head radiographs comprising two series:
      (1) 85 films of children with Class II, division 1 malocclusion and (2) 62 films
      of children with "normal" occlusion. Age range of the representing children was
      10-13 years. RESULTS: In Class II division 1 subjects, the maxilla was prognathic
      in relation to anterior cranial base. The mandible was normally positioned in
      relation to anterior cranial base. Upper incisors were proclined and lower
      incisors were normally positioned. The cranial base angle was not different
      between the two groups. CONCLUSIONS: In the western region of Saudi Arabia, Class
      II division 1 malocclusion has specific characteristics. The presence of
      prognathic maxilla, in this sample, indicates that the use of head gear therapy
      might be more appropriate than functional appliances when treating Class II
      division 1 malocclusion in Saudis living in the Western region.

PMID- 23960499
TI  - Dental practitioner's knowledge, opinions and methods of management of oral
      premalignancy and malignancy.
AB  - OBJECTIVES: The present study outlines the results of a pilot study to determine
      the knowledge and awareness of a cohort of dentists in United Arab Emirates (UAE)
      regarding aetiology, clinical features and appropriate early management of oral
      premalignant and malignant lesions. MATERIALS AND METHODS: A self-administered
      questionnaire was constructed and posted to 300 UAE Dental Practitoners (DPs),
      selected randomly from the register of Emirates Dental Association. The present
      report details the responses of this cohort. RESULTS: 182 questionnaires were
      completed and returned (response rate 60.6%). One hundred and twenty-seven
      (69.8%) of the responding dentists were male and the median age of the DPs was 40
      years (range 24-75 years). The majority (84%) practised or had practised in or
      around Dubai and Sharjah, 75% had graduated from a dental school after 1980.
      Eighty-two respondents (45.0%) had attended specific courses on premalignant or
      malignant oral lesions. During their undergraduate training 70% of DPs had
      witnessed more than 10 patients with oral SCC. Only 60.4% of respondents
      indicated that the tobacco and alcohol use were the principle causes of oral SCC
      while 19.7% suggested that HIV disease was a risk factor for oral SCC. 29% of DPs
      routinely recorded the tobacco or alcohol use of their patients and only 3.8%
      offered advice to patients regarding modification of these habits. Eight-three
      percent of the respondents suggested that clinical screening was an effective
      means of reducing the frequency of premalignant and malignant oral lesions.
      CONCLUSIONS: In view of the gradual rise in oral malignancy worldwide there is an
      increased need for DPs to be able to recognize the signs and symptoms of oral
      malignancy and premalignancy, provide appropriate preventive advice and be aware
      of the appropriate early management of patients with such oral lesions.

PMID- 23960500
TI  - Canine location in different maxillomandibular relationships in Egyptians and
      Saudis.
AB  - The standards or proportions commonly used as guides for the selection of
      maxillary anterior teeth for a removable prosthesis have been developed mainly on
      Caucasian populations with normal ridge relationships. PURPOSE: This study was
      conducted to determine the canine position in relation to commissures in
      different maxillomandibular relationships among Egyptian and Saudi populations.
      MATERIAL AND METHODS: Two hundred subjects participated in this study, 100 from
      each population. The location of the corners of the mouth for each subject was
      marked on the buccal surface of a screen previously constructed on the maxillary
      cast and transferred to the casts. The distances between the corners of the mouth
      and the canines' distal aspect were measured on the casts. The measurements were
      subdivided according to their relation to the commissures: at commissures, medial
      to commissures, or distal to commissures. The data were then statistically
      analyzed. RESULTS: Coincidence between the canine distal aspects and commissures
      was recorded only within 8% of both Egyptian and Saudi populations. Additionally,
      within the Egyptian population, coincidence was recorded only at Class-I ridge
      relationship. CONCLUSION: Commissures are not a reliable landmark for
      determination of the distal aspect of the canine distal aspects of both Egyptian
      and Saudi populations.

PMID- 23960501
TI  - Initial experience with hemostatic fibrin glue as adjuvant during drainless
      parotidectomy.
AB  - OBJECTIVES: To evaluate the use of Hemostatic Fibrin Glue in parotidectomy
      without the use of surgical drains. STUDY DESIGN: Prospective cohort study of 10
      patients undergoing parotidectomy. Surgery as a one day admission without the use
      of surgical drains was planned. The complication and duration of the hospital
      stay were obtained. METHODS: Parotidectomy was undertaken by one surgeon. Prior
      to wound closure, the skin flap and wound bed were approximated using Tisseel
      tissue sealant. Data regarding the incidence of any complication and the duration
      of the hospital stay were obtained. Patients were followed to assess surgical
      outcome and document any complications. The mean follow-up period was 8 months
      (range 4-12 months). RESULTS: There were no major surgical complications. Two
      patients had facial nerve weakness due to adherence of the tumour in the facial
      nerve, in there was which complete recovery after few months. All patients were
      discharged the next day. None of the patients felt that the discharge had been
      premature. CONCLUSIONS: Parotidectomy can be undertaken safely without the need
      for surgical drains, therefore, allowing the patients to leave the hospital on
      the first postoperative day.

PMID- 23960502
TI  - Mandibular cephalometric characteristics of a Saudi sample of patients having
      impacted third molars.
AB  - OBJECTIVE: To evaluate the cephalometric characteristics of mandibles of Saudi
      patients having impacted third molars and to compare them to those of patients
      having normally erupted third molars. MATERIAL AND METHODS: One hundred and
      twenty-one Saudi adult subjects (59 females and 62 males; age: 20-40 years) were
      divided into two groups based on the status of the mandibular third molars: (1)
      impaction group and (2) normal group. Means and standard deviations of 21
      cephalometric measurements related to mandibular geometry were measured and
      compared between the two groups using the unpaired t-test. Males and females in
      the impaction group were also compared with their equivalent subgroups in the
      normal group using the unpaired t-test. RESULTS: Anteroposteriorly, space distal
      to second molar, ramal width and mandibular body length were significantly less
      in the impaction group than in the control group. In addition, posterior teeth
      were more upright in the impaction group. Vertically, posterior alveolar height
      was significantly less in the impaction group. The Y-axis was significantly
      increased in the impaction group. The significance of these measurements was
      variable between males and females. CONCLUSIONS: Third-molar impactions in the
      Saudis living in the Western region of Saudi Arabia were more likely to occur
      when inadequate retromolar space is present. This can be attributed to certain
      mandibular skeletal and dental features, among which the increased width of
      mandibular ramus and backward inclination of posterior teeth seem to be the most
      influencing factors in both sexes.

PMID- 23960503
TI  - Postgraduate specialties interest, career choices and qualifications earned by
      male dentists graduated from King Saud University.
AB  - OBJECTIVES: To study the career development of male graduates of King Saud
      University (KSU), College of Dentistry in terms of pursuit of postgraduate dental
      education, higher degrees or Board Certification, choice of universities and
      countries of study, and place of work after qualification. METHODS: A
      questionnaire survey was carried out through face to face or telephone interview
      among 666 KSU graduates of 1982-2004. RESULTS: 80% (532 graduates) response rate.
      (77%) finished postgraduate dental education. 17% specialized in Prosthodontics,
      16% in Saudi Board Advanced Restorative Dentistry, 14% in Advanced General
      Dentistry, 10.5% in Orthodontics, 10% in Oral and Maxillofacial Surgery, 8.3% in
      Pediatric Dentistry, 7.7% in Endodontics, 6% in Periodontics, 5.5% in Operative
      Dentistry, 5% in other Specialties. 61% had a Master's degree and 16% had a
      Doctorate degree. 23% had Board Certificates and 8% had a Fellowship Certificate.
      (78%) are working in the government, 15% at the university and 6% in private, and
      19% in administrative positions. CONCLUSION: Most of the dental graduates were
      motivated and eager to continue their postgraduate education to get either
      clinical specialty or academic degrees from nationally and internationally well
      recognized and known Universities and programs.

PMID- 23960504
TI  - Factors affecting efficacy of oral trimeprazine sedation for dental procedures in
      children: A retrospective study.
AB  - OBJECTIVE: To investigate the influence of factors such as age, gender and pre
      operative behavior rating on the outcome of sedation using oral trimeprazine
      during dental treatment of children. METHOD: Records of children who received
      dental treatment under sedation with oral trimeprazine between 2000 and 2007 were
      reviewed and the following data were obtained: age and weight of patient at the
      time of treatment, gender, behavior classification prior to sedation, dose of
      medication used, efficacy of sedation and treatment accomplished. Descriptive
      statistics, cross-tabulations and chi (2) analysis were done. RESULT: Forty-eight
      sedation sessions met the inclusive criteria for children whose mean age was 4.92
      (SD 1.65, range 3.0-8.0) years and mean weight was 18.23 (SD 4.82, range: 12.0
      31.0) kg. Overall, 54.2% (26/48) of the sedations were rated successful, 20.8%
      (10/48) were partially successful and 25.0% (12/48) not successful. Younger
      children 3-5 years, and those with only negative pre-operative behavior rating
      had more successful sedation sessions than older, 6-8 years or children with
      definitely negative pre-operative behavior rating (X (2) = 8.165, p = .017) and
      (X (2) = 17.258, p = .001), respectively. CONCLUSION: Variables such as patient's
      age and pre-operative behavior but not gender and type of treatment could predict
      outcome of dental sedation using trimeprazine in children.

PMID- 23960505
TI  - A morphological survey of root grooves and their influence on periodontal
      attachment loss.
AB  - Periodontal health reflects a balance between harmful and protective elements in
      the gingival marginal area. The total plaque mass, specific periodontopathogens,
      the tooth morphology, and local environmental factors may challenge this balance.
      The periodontal ligament attachment loss shifts this balance adversely toward the
      periodontal disease. OBJECTIVES: The aim of this retrospective study was to
      determine the significance of proximal root grooves as a risk factor in the
      periodontal attachment loss; the effect of their dimensions and locations has
      been evaluated. MATERIALS AND METHODS: One hundred (100) extracted formalin
      stored single rooted permanent anterior teeth were studied by staining with 0.1%
      toludine blue to visualize attached periodontal ligament remnants. On each tooth,
      the loss of attachment was measured from the cemento-enamel junction to the most
      coronal level of the stained periodontal ligament remnants. RESULTS: The
      prevalence of proximal root grooves was found to be 81% and a statistically
      significant greater loss of attachment was present on grooved than on non-grooved
      surfaces (p < 0.01). CONCLUSIONS: Generally, there was direct relationship
      between groove location, its dimensions, and maximum loss of attachment. The
      results suggest that proximal root grooves should be considered in periodontal
      diagnosis, prognosis, and treatment planning.

PMID- 23960506
TI  - Distance between implants has a potential impact of crestal bone resorption.
AB  - OBJECTIVES: Around dental implants exists a "biologic width" of few millimeters
      that have to be preserved in order to not have adverse effect on soft and hard
      tissues around implant. Because the minimum distance between adjacent implants
      has not been determined yet, we therefore, decided to perform a retrospective
      study on a series of spiral family implants (SFIs) to verify the minimum inter
      implants' distance that has an impact on crestal bone resorption. MATERIALS AND
      METHODS: Fifty-nine implants were investigated with a mean follow-up of 14
      months. Implant diameter was 3.75, 4.2, 5 and 6 mm in 11 (18.6%), 29 (49.2%), 17
      (28.8%) and 2 (3.4%) SFIs. Implant length was shorter than 13 mm, equal to 13 mm
      and 16 mm in 23 (39%), 23 (39%) and 13 (22%) SFIs. Implants were inserted to
      replace 13 incisors (22%), 7 cuspids (11.9%), 30 premolars (50.8%) and 9 molars
      (15.3%). Twenty-seven fixtures were inserted in post-extractive sockets and the
      remaining 32 in healed bone; 36 (61%) were immediately loaded. In addition to the
      above mentioned implant-related factors, several host- and surgery-factors were
      investigated. Independent samples T-test, univariate and multivariate analysis
      were used to detect those variables associated with the clinical outcome.
      RESULTS: Data were evaluated with a two steps statistical analysis (i.e.
      univariate and multivariate) after having grouped implants in two series: those
      with an implant-implant distance less of 1.8 mm and those with an implant
      implants distance greater than 1.8 mm. In univariate analysis, post-extractive
      implants and number of prosthetic units were statistically significant. In
      multivariate analysis, only post-extractive implants have a significant adverse
      effect on crestal bone resorption. CONCLUSIONS: Adjacent implants inserted with a
      distance lower and higher than 1.8 mm have difference in crestal bone resorption
      but this difference is not statistically significant in a short period follow up.
      This could due to the specific implant used that has a reverse conical neck. No
      statistical difference was detected between implant subtypes. Post-extractive
      implant insertion is the major determinant in terms of peri-implant bone
      resorption in a short period follow-up.

PMID- 23960507
TI  - Short term clinical effectiveness of a 0.07% cetylpyridinium chloride mouth rinse
      in patients undergoing fixed orthodontic appliance treatment.
AB  - OBJECTIVES: To test the short term clinical effectiveness of commercially
      available 0.07%.cetylpyridinium chloride mouth rinse in patients undergoing fixed
      orthodontic treatment as compared to a placebo mouth rinse and patients using
      toothbrush and toothpaste. METHOD: Forty-five subjects for this double blind
      study were assigned randomly into three groups of 15 each. Gingival inflammation,
      plaque accumulation, and bleeding on probing, were recorded at baseline (10 days
      after prophylaxis), and at the end of one month in all the three groups and
      compared. RESULTS: Paired t test showed significant differences in bleeding index
      for pre and post treatment recordings for cetylpyridinium group. Modified
      gingival index showed no significant difference in the cetylpyridinium group. For
      plaque index significant difference was found for cetylpyridinium and control
      groups. CONCLUSION: Cetylpyridinium mouth rinse 0.7% was found to be effective in
      reducing the bleeding and plaque index scores. It was not effective in reducing
      the modified gingival index scores. Cetylpyridinium mouth rinse 0.07% improves
      the oral hygiene of orthodontic patients when used as an adjunct to normal oral
      hygiene measures.

PMID- 23960508
TI  - The effect of locally delivered doxycycline as an adjunctive therapy to scaling
      and root planing in smokers.
AB  - BACKGROUND: Locally delivered doxycycline is found to be effective in managing
      periodontitis as an adjunct to scaling and root planing. AIM: To evaluate the
      effect of locally delivered doxycycline (10%) with scaling and root planing in
      the periodontal treatment of smokers and to compare it with scaling and root
      planing alone. METHODS: Twelve smokers with chronic periodontitis and a pocket
      depth (?5 mm) on posterior teeth that bleed on probing were selected. Patients
      were randomly assigned to scaling and root planing (SRP) or scaling and root
      planing followed by local application of doxycycline (SRP-D). Plaque, bleeding on
      probing, gingival recession, clinical attachment level (CAL), and probing depth
      (PD) were recorded at the baseline, 6 and 12 weeks. RESULTS: Both groups showed a
      significant reduction in Plaque, Bleeding on Probing and pocket depth at 6th and
      12th week from the baseline. A statistically significant gain of attachment was
      observed in both groups after treatment. Even though the doxycycline group showed
      slightly higher attachment gain it was not statistically significant compared to
      the control group. CONCLUSION: The observations of the study reveal that the
      additional benefit of topical application of doxycycline as an adjunct to scaling
      and root planing in smokers is not convincing. However, further clinical studies
      may be necessary to substantiate the present observations.

PMID- 23960510
TI  - Experience of wrong-site tooth extraction among Nigerian dentists.
AB  - OBJECTIVE: To report the experience of wrong-site tooth extraction among Nigerian
      dentists. STUDY DESIGN: A self-administered questionnaire was distributed among a
      cross-section of Nigerian dentists. Information requested included personal
      experience on wrong-site tooth/teeth extraction and its after-effect, possible
      reasons for wrong-site tooth extraction and documentation of the event in
      patients' case. Respondents were also asked if they were aware of any colleagues
      who had previously experienced wrong-site tooth extraction and possible legal
      implication of the event, and if they aware of the universal protocol for
      preventing wrong site, wrong procedure, and wrong person surgery. RESULTS: Twenty
      two (13%) of the respondents reported having extracted a wrong tooth. The event
      occurred within 5 years after graduation in most cases. Most respondents (53.6%)
      informed the patient immediately after the event. Only 68% of the respondents
      documented the event in patient's case record. Most common reasons for wrong-site
      tooth extraction were heavy workload, presence of multiple condemned teeth and
      miscommunication between dentists. Fifty-five percent of respondents were aware
      of a colleague who had extracted a wrong tooth. The most probable legal
      implication of wrong-site tooth extraction according to the respondents was
      litigation by the patient. Only 25% of dentists were aware of a universal
      protocol for preventing wrong-site surgery. CONCLUSIONS: Wrong tooth/teeth
      extraction is not an uncommon event in the studied environment. The need to be
      familiar with universal protocol on wrong-site surgery and its legal implications
      are highlighted.

PMID- 23960511
TI  - Prescribing a dental ceramic material: Zirconia vs lithium-disilicate.

PMID- 23960509
TI  - The impact of pH on cytotoxic effects of three root canal irrigants.
AB  - AIM: Cytotoxicity of root canal irrigants is important due to their close contact
      with host tissues. This study was to assess the possible impact of pH on
      cytotoxic effects of MTAD, 17% EDTA, and 2.6% NaOCl on the human gingival
      fibroblasts using MTT assay. MATERIALS AND METHODS: Human gingival fibroblasts
      were exposed to the irrigants and their viability was assessed after 1, 6, and 12
      h. The pH of the medium was measured in each interval. Light absorption values
      were measured for each culture medium using Elisa Reader device. RESULTS: NaOCl
      had significantly less cytotoxicity than EDTA and MTAD. Also irrigants
      cytotoxicity decreased in 12, 1, and 6 h, respectively. CONCLUSION: It seems that
      variation of the pH resulted in variation in the cytotoxicity of solutions; i.e.,
      it follows the pattern of the pH variation.

PMID- 23960512
TI  - Intrusive luxation in primary teeth - Review of literature and report of a case.
AB  - Luxation injuries such as intrusion are commonly seen in the primary dentition.
      Intrusion drives the tooth deeper into the alveolar socket, which results in
      damage to the pulp and peridontium. Difficulty in gaining compliance from a very
      young child and the risk of damaging the permanent tooth germ makes the
      management of these injuries challenging. Careful clinical and radiographic
      examination along with regular follow-up is essential. A case of intrusive
      luxation to the maxillary central incisor in a 3-year-old patient is reported.
      Spontaneous reeruption was noted 4 months after injury, but the tooth had
      developed an abscess and external root resorption. Hence, extraction of the tooth
      was done and an anterior esthetic fixed space maintainer was placed. Traumatic
      injuries to the primary dentition should not be ignored by the parents or by the
      dentist. The paper also includes a literature review of intrusive luxation in the
      primary dentition. 

PMID- 23960513
TI  - Accidental ingestion of foreign object: Systematic review, recommendations and
      report of a case.
AB  - One of the serious complications during a routine endodontic procedure is
      accidental ingestion/aspiration of the endodontic instruments, which can happen
      when proper isolation is not done. There are at present no clear guidelines
      whether foreign body ingestion in the gastrointestinal tract should be managed
      conservatively, endoscopically or surgically. A 5 year old boy reported to the
      Department of Pediatric and Preventive Dentistry, D.A. Pandu Memorial R.V. Dental
      College, Bangalore, India, with a complaint of pain and swelling in the lower
      right back teeth region. Endodontic therapy was planned for the affected tooth.
      During the course of treatment the child accidentally swallowed a 21 mm 15 size K
      file. Endoscopy was performed immediately but the instrument could not be
      retrieved. The instrument passed out uneventfully along with the stools 48 h
      after ingestion. Careful evaluation of the patient immediately after the accident
      helps in managing the patient effectively along with following the recommended
      guidelines. 

PMID- 23960514
TI  - Ethnic differences in dentofacial relationships of Turkish and Saudi young adults
      with normal occlusions and well-balanced faces.
AB  - OBJECTIVES: The aims of the present study were (1) to determine ethnic
      differences in craniofacial dimensions between Turkish and Saudi populations and
      (2) to identify possible gender differences between males and females, based on a
      sample of untreated young adult subjects with normal occlusions and well-balanced
      faces. METHODS: In total, 163 cephalometric radiographs were traced and evaluated
      to compare untreated adults of Turkish and Saudi ethnicity. The Turkish group
      comprised 86 subjects; 45 females and 41 males. The Saudi group comprised 77
      subjects; 39 females and 38 males. For statistical evaluation, an independent
      samples t-test was performed. RESULTS: The Turkish sample had a more retrognathic
      maxilla and mandible (p < 0.001 for SNA and SNB) and a more vertical direction of
      facial development (p < 0.001), with Turkish males having more retrusive lips (p
      < 0.001). Distinctive ethnic differences were found in craniofacial structures
      between Turkish and Saudi young adults. CONCLUSIONS: It is appropriate to
      consider these aesthetic differences when a Turkish or a Saudi patient is being
      evaluated during routine diagnosis and treatment planning.

PMID- 23960515
TI  - Evaluation of facial soft tissue parameters for Palestinians using Holdaway
      analysis.
AB  - OBJECTIVE: The aims of this study were to evaluate soft-tissue measurements for a
      Palestinian sample population with normal occlusion by Holdaway's analysis, and
      to check the applicability of Holdaway values to the Palestinian population.
      Normal Holdaway values for Palestinians will be established if their parameters
      do not match those of Holdaway. MATERIAL AND METHODS: Cephalometric radiographs
      of 93 Palestinian university students with normal occlusion (63 women, mean age:
      20.1 +/- 2.1 years; 30 men, mean age: 20.2 +/- 2.4 years) were traced and
      evaluated. Cephalometric landmarks were located according to Holdaway analysis.
      Ten linear and two angular measurements were produced on each radiograph.
      RESULTS: The soft-tissue measurements for the Palestinians were similar to the
      Holdaway norms, except for the soft-tissue convexity angle and soft-tissue chin
      thickness, which were larger than the Holdaway averages. The Palestinian sample
      had a narrower range for normal nose prominence, as well as thicker lips, deeper
      superior and inferior sulci, and thicker soft-tissue chins than the Holdaway
      values. CONCLUSIONS: We determined normal values for the Holdaway soft-tissue
      analysis for Palestinians, which are appropriate for use in orthodontic practices
      in these territories.

PMID- 23960516
TI  - Variation of pediatric and adolescents head and neck pathology in the city of
      Jeddah: A retrospective analysis over 10 years.
AB  - This study was conducted to present a comprehensive view of the most common head
      and neck pathologies among the pediatric and adolescent population of the city of
      Jeddah, Saudi Arabia. Data were collected from the oral and maxillofacial surgery
      (OMFS) records at King Abdulaziz University Hospital and King Fahad Hospital
      Jeddah (KFHJ) from the period 1998 to 2009. All patients who were 18 years of age
      and younger were included in the study. Identified lesions were classified into
      four categories: cystic, neoplastic, vascular and fibro-osseous. Age and sex
      distribution of the lesions were also calculated. A total of 155 patients were
      included in this study. Of all the lesions, 143 (92.26%) were benign and 12
      (7.74%) were malignant; 63 (40.65%) were cysts; 48 (30.97%) were neoplasms; 23
      (14.84%) were vascular and 21 (13.55%) were fibro-osseous tumors. The most common
      lesions were hemangioma (20 cases; 12.9%) followed by retention cyst (19 cases;
      12.26%) and dentigerous cyst (15 cases; 9.68%). The most common benign
      odontogenic neoplasm was odontoma (7 cases; 4.52%), of which central giant cell
      granuloma (6 cases; 3.87%) was the most frequent benign nonodontogenic tumor and
      lymphoma (6 cases; 3.87%) was the most common malignant one. Although this study
      might benefit clinicians in guiding them through differential diagnosis of
      pediatric and adolescent head and neck pathology in reference to their sex and
      age groups, governmental efforts are badly needed to establish a Saudi childhood
      pathology registry. 

PMID- 23960517
TI  - Postgraduate training in orthodontics in the UK.
AB  - This article briefly describes the postgraduate pathways in orthodontics in the
      United Kingdom. It is hoped that this will assist potential trainees who want to
      pursue postgraduate training to understand the different career pathways
      available to them. It may also add to the knowledge of some senior colleagues who
      can explain these career opportunities to their students, as not all potential
      trainees will have the opportunity to read this article. In the following pages
      we will discuss the different pathways leading to specialist qualification in
      orthodontics, in the United Kingdom. 

PMID- 23960518
TI  - Esthetic soft tissue ridge augmentation around dental implant: Case report.
AB  - The aim of this case report is to present a method to correct soft tissue ridge
      deformity around dental implant using acellular dermal matrix (ADM). A 25-year
      old female patient presented with a missing maxillary first left premolar, which
      had class I soft tissue defect. The missing tooth was replaced with single
      implant supported prosthesis and the soft tissue defect was corrected using ADM
      utilizing the envelop technique. A 5-years follow-up is presented showing the
      long-term stability of this technique and the predictability of using the ADM as
      an alternative method to connective tissue graft to correct the soft tissue
      defect around dental implant. 

PMID- 23960520
TI  - The need for a 'Patient Safety in Dentistry Initiative' in the Gulf States.

PMID- 23960519
TI  - Eagle's syndrome - A case report and review of the literature.
AB  - Eagle's syndrome (ES) occurs when an elongated styloid process or calcified
      stylohyoid ligament causes recurrent throat pain or foreign body sensation,
      dysphagia, or facial pain. Additional symptoms may include neck or throat pain
      with radiation to the ipsilateral ear. The symptoms related to this condition can
      be confused with those attributed to a wide variety of facial neuralgias. ES can
      be diagnosed radiologically and by physical examination. The treatment of ES is
      primarily surgical. The styloid process can be shortened through an intraoral or
      external approach. In this paper a case of ES exhibiting unilateral symptoms with
      bilateral elongation of styloid process is reported and the literature is
      reviewed. 

PMID- 23960521
TI  - Prevalence of orofacial clefts in Saudi Arabia and neighboring countries: A
      systematic review.
AB  - Cleft lip and/or palate are among the most common birth defects in the world. The
      prevalence of these conditions varies considerably across geographic areas and
      ethnic groups. OBJECTIVE: The aim of this study was to carry out a systematic
      review and appraisal of the literature on the prevalence of cleft lip and/or
      palate in Saudi Arabia and comparable Middle Eastern countries. MATERIALS AND
      METHODS: All published articles on orofacial clefts (OFC) in Saudi Arabia and its
      bordering countries in the Middle East with similar and comparable population
      characteristics were reviewed in July 2010. RESULTS: After reviewing the
      articles, only eight matched the inclusion criteria. Three studies were carried
      out in two regions in Saudi Arabia (Riyadh and Al-Qaseem). The other five studies
      were set in Dubai, Oman, and Jordan. The prevalence of cleft lip and/or palate
      reported in these studies varied greatly from 0.3 to 2.4 per 1000 live births.
      The birth prevalence of orofacial clefts in males was reported to be higher than
      in females. The isolated cleft palate prevalence was reported to be higher in
      females in most of the studies. CONCLUSION: The eightfold variation in the
      prevalence of orofacial clefts between highest and lowest prevalence is likely to
      be due, at least in part, to problems with ascertainment, but there may also be
      underlying genetic or environmental factors that require further investigation.

PMID- 23960522
TI  - Factors associated with hematoma of the floor of the mouth after placement of
      dental implants.
AB  - PURPOSE: The aim of this article is to determine factors associated with hematoma
      during placement of dental implants in the anterior mandible and to provide the
      dental practitioner with preventive measures to avoid such a life-threatening
      complication. METHODS: All available clinical case studies from (1986 to 2010)
      published in English or with English abstract were reviewed and analyzed.
      RESULTS: Nineteen studies have been identified and written in the literature.
      Most of the reported studies were case series and they showed that hematoma is a
      very rare complication, but general dental practitioners do not pay attention to
      the significance of the mandible anatomy in the anterior area and the possibility
      of perforation of the lingual cortex during placement of the dental implants in
      that position. CONCLUSIONS: The use of dental CT in planning the implant
      treatment coupled with accurate determination of implant length in order to
      provide detailed data about the mandible anatomy are highly recommended to avoid
      the occurrence of hematoma in the floor of the mouth and the airway obstruction
      that may lead to death during placement of dental implants in the anterior
      mandible.

PMID- 23960523
TI  - Elevation of white blood cells and platelet counts in patients having chronic
      periodontitis.
AB  - BACKGROUND AND AIM: Many risk factors that might contribute to the pathogenesis
      of atherosclerosis have been proposed, including chronic inflammation and
      infection. Furthermore, systemic inflammatory responses to periodontal bacteria
      have been suggested as a pathogenetic link between periodontal disease and
      atherosclerosis. The purpose of this study was to estimate the white blood cell
      (WBC) and platelet counts in chronic periodontitis patients. MATERIALS AND
      METHODS: Fifty patients with chronic periodontitis and 50 patients with healthy
      periodontium were included in this study. Oral hygiene status, pocket probing
      depth (PPD) and clinical attachment level (CAL) were measured. During clinical
      evaluation, venous blood samples were taken to analyze the WBC and platelet
      counts. Statistical analysis was utilized to compare differences across groups.
      RESULTS: Periodontitis patients demonstrated a significantly higher WBC count
      (7.22 +/- 1.42 * 10(9) cells/L) than that of control patients (5.64 +/- 1.56 *
      10(9) cells/L; P < 0.001). The platelet count of patients with chronic
      periodontitis (290.73 +/- 56.56 * 10(9) cells/L) was also significantly higher
      compared to the healthy group (223.37 +/- 50.27 * 10(9) cells/L; P < 0.001).
      CONCLUSION: Levels of WBCs and platelets are elevated in periodontitis patients
      compared to healthy controls.

PMID- 23960524
TI  - Shear bond strength between light polymerized hard reline resin and denture base
      resin subjected to long term water immersion.
AB  - STATEMENT OF THE PROBLEM: The effect of long-term water immersion on the shear
      bond strength between denture base resin and Triad visible-light-polymerized
      (VLP) direct hard reline resin is not known. PURPOSE: The aim of this study was
      to investigate the bonding characteristics of Triad VLP direct hard reline resin
      to heat-polymerized denture base resin subjected to long-term water immersion.
      MATERIAL AND METHODS: Ninety circular disks, 15 mm in diameter and 3 mm thick, of
      denture base resin were polymerized from a gypsum mold. Sixty specimens were
      subjected to water immersion and 30 were stored at ambient room temperature for 4
      months. Thirty water-immersed specimens were dried with gauze (group 1), while
      the other 30 water-immersed specimens were dried with a hair dryer (group 2). The
      dry specimens (n = 30) represented the control group (group 3). All specimens
      were air abraded and painted with bonding agent before packing Triad VLP direct
      hard-reline resin. Specimens in each group were subjected to thermal cycling for
      50,000 cycles between 4  degrees C and 60  degrees C water baths with 1-min dwell
      time at each temperature. The bond strength at which the bond failed under stress
      was recorded using a universal testing machine. One-way ANOVA and Tukey post hoc
      comparison were applied to find significant differences between groups (alpha =
      0.05). RESULTS: Significant differences in mean shear bond strength among the
      specimens existed because of variable water content in the denture base resin (P
      < 0.05). Group 3 (dry) was higher than group 2 (desiccated), and the lowest was
      group 1 (saturated). CONCLUSION: The shear bond strength of Triad VLP direct hard
      reline resin to denture base resin depended on the water content in the denture
      base resin. The dry denture base resin demonstrated superior bond strength
      compared with the desiccated and water-saturated denture base resins.

PMID- 23960525
TI  - Career characteristics and postgraduate education of female dentist graduates of
      the College of Dentistry at King Saud University, Saudi Arabia.
AB  - OBJECTIVES: The aims of this study were to investigate the number of female
      bachelor of dental surgery graduates who earned postgraduate education degrees
      from King Saud University, their specialties, degrees of qualification, and
      countries of graduation. METHODS: A questionnaire survey was conducted through
      face-to-face or phone interview among 677 female dentists who graduated from the
      College of Dentistry at King Saud University between 1984 and 2006. RESULTS: Five
      hundred forty-five (81%) graduate female dentists responded, of whom 54% had
      completed postgraduate dental education. In the Saudi Board, 17% had obtained
      degrees in advanced restorative dentistry, 15% in pediatric dentistry, 14% in
      advanced general dentistry, 11% in orthodontics, 10% in prosthodontics, 8% in
      operative dentistry, 5% in endodontics, 5% in periodontics, 3% in oral and
      maxillofacial surgery, and 11% in other specialties. Fifty-nine percent had
      master's degrees, 7% had doctorates, 32% had board certificates, and 2% had
      fellowship certificates. CONCLUSION: More than half (54%) the female dentists
      surveyed had pursued postgraduate education. This investigation highlighted the
      different specialties enrolled by female dentists. Orthodontic post graduate
      program displayed the highest percentage of interest. Understanding the
      unavoidable social family needs and the demand for higher education by female
      dentists provides ideas as more programs should be planned to accommodate the
      needs of Saudi female dentists. This type of study should be repeated due to the
      increasing interest of female dentists in higher education.

PMID- 23960526
TI  - An evaluation of microleakage of various glass ionomer based restorative
      materials in deciduous and permanent teeth: An in vitro study.
AB  - AIM: To evaluate the microleakage of recently available glass ionomer based
      restorative materials (GC Fuji IX GP, GC Fuji VII, and Dyract) and compare their
      microleakage with the previously existing glass ionomer restorative materials (GC
      Fuji II LC) in primary and permanent teeth. METHOD: One hundred and fifty (75 +
      75) non-carious deciduous and permanent teeth were restored with glass ionomer
      based restorative materials after making class I cavities. Samples were subjected
      to thermocycling after storing in distilled water for 24 h. Two coats of nail
      polish were applied 1 mm short of restorative margins and samples sectioned
      buccolingually after storing in methylene blue dye for 24 h. Microleakage was
      assessed using stereomicroscope. RESULT: Significant differences (P < 0.05) were
      found when inter group comparisons were done. Except when GC Fuji VII (Group III)
      was compared with GC Fuji II LC (Group II) and Dyract (Group IV), non-significant
      differences (P > 0.05) were observed. It was found that there was no
      statistically significant difference when the means of microleakage of primary
      teeth were compared with those of permanent teeth. CONCLUSIONS: GC Fuji IX GP
      showed maximum microleakage and GC Fuji VII showed least microleakage.

PMID- 23960527
TI  - Setting up of teeth in the neutral zone and its effect on speech.
AB  - Rational goals for denture construction are basically directed at the restoration
      of esthetics and masticatory function and the healthy preservation of the
      remaining natural tissues. Little concern has been given to the perfection and
      optimization of the phonetic quality of denture users. However, insertion of
      prosthodontic restorations may lead to speech defects. Most such defects are mild
      but, nevertheless, can be a source of concern to the patient. For the dental
      practitioner, there are few guidelines for designing a prosthetic restoration
      with maximum phonetic success. One of these guidelines involves the setting up of
      teeth within the neutral zone. The aim of this study was to evaluate,
      subjectively and objectively, the effect on speech of setting up teeth in the
      neutral zone. Three groups were examined: group I (control) included 10
      completely dentulous subjects, group II included 10 completely edentulous
      patients with conventional dentures, and group III included the same 10
      edentulous patients with neutral zone dentures. Subjective assessment included
      patient satisfaction. Objective assessment included duration taken for recitation
      of Al-Fateha and acoustic analysis. Subjectively, patients were more satisfied
      with their neutral zone dentures. Objectively, speech produced with the neutral
      zone dentures was closer to normal than speech with conventional dentures. 

PMID- 23960528
TI  - Orthodontic elastic band-induced periodontitis - A case report.
AB  - Periodontal problems due to the use of elastic bands have been documented in the
      past. A 9-year-old girl reported to a periodontist with complaints of bleeding
      from gums and tooth mobility of upper right central incisor. This case, reports
      the early diagnosis and treatment of an acute localized periodontitis arising
      from the incorrect use of orthodontic elastic rubber bands to close a maxillary
      midline diastema. The elastic band induced periodontitis was treated with a
      combination of surgery, splinting, antibiotics and orthodontics. Removal of the
      etiologic agent improved the condition of the tooth. 

PMID- 23960530
TI  - Engineering of dental tissues; reality or distant prospect.

PMID- 23960529
TI  - MTA resorption and periradicular healing in an open-apex incisor: A case report.
AB  - This case report describes the periradicular healing and resorption of an
      unintentional extrusion of mineral trioxide aggregate (MTA) in an open-apex
      central incisor. A 22-year old female with a symptomatic open-apex right
      maxillary central incisor associated with a periradicular lesion was referred for
      evaluation and treatment. After chemomechanical debridement, the apical third of
      the root canal was filled with MTA to create an apical plug. Postoperative
      radiographs showed the extrusion of MTA into the periradicular lesion. The tooth
      was then restored with a post and crown. At the 2-year follow-up, the tooth was
      asymptomatic and radiographs revealed complete healing of the periradicular area.
      At the 7-year follow-up, complete resorption of the extruded MTA was evident. The
      results of this case study indicate that complete resorption of extruded MTA is
      possible in the long term; however, the extrusion of MTA in open-apex tooth
      should still be avoided. 

PMID- 23960531
TI  - A review on miswak (Salvadora persica) and its effect on various aspects of oral
      health.
AB  - Plants have been used for centuries to improve dental health and to promote oral
      hygiene, and this practice persists in several communities throughout the world.
      "Miswak" is an Arabic word meaning "tooth-cleaning stick," and Salvadora persica
      miswak has a wide geographic distribution. It was used by ancient Arabs to whiten
      and polish the teeth. This review discusses the history and chemical composition
      of S. persica miswak and its influence on oral health, including the advantages
      and disadvantages of its use. 

PMID- 23960532
TI  - The efficacy of Salvadora persica extract in the elimination of the intracanal
      smear layer: A SEM study.
AB  - AIM: To evaluate the efficacy of an ethanolic Salvadora persica extract in
      removing the smear layer following a root canal procedure. METHODS: Sixty
      extracted, single-rooted human teeth were cleaned, shaped, and divided into four
      groups. Experimental groups 1 (n = 20) and 2 (n = 20) were irrigated with 1 mg/ml
      and 5 mg/ml of S. persica, respectively. The positive controls (n = 10) were
      irrigated with 17% ethylenediaminetetraacetic acid (EDTA), while the negative
      controls (n = 10) were irrigated with saline. Approximately 5 ml of the
      irrigating solution was delivered into the root canals for 5 min, and the final
      rinse was performed with 5 ml of 1% sodium hypochlorite. Scanning electron
      microscopy was used to evaluate the endodontic smear layer removal at the
      coronal, middle, and apical thirds of the specimens. RESULTS: A significant
      difference in smear layer removal between groups 1 and 2 at the coronal and
      middle thirds of the canal was observed, and no significant difference was seen
      between group 2 and the positive control at the coronal third. At the apical
      third, both concentrations of S. persica had similar effects and were less
      effective than the positive control in removing the smear layer. CONCLUSION: The
      5 mg/ml S. persica solution was significantly more effective than the 1 mg/ml
      solution. In addition, the 5 mg/ml S. persica solution was as effective as 17%
      EDTA in removing the smear layer from the coronal third of the canal wall.

PMID- 23960533
TI  - The influence of resin infiltration system on enamel microhardness and surface
      roughness: An in vitro study.
AB  - OBJECTIVE: To investigate the effect of a resin infiltrant on the surface
      microhardness and roughness of healthy enamel and, as a subsidiary aim, to
      compare it with a fissure sealant. MATERIALS AND METHODS: Twenty freshly
      extracted premolars were used. Sound enamel surfaces were treated with a resin
      infiltrant (Icon) or fissure sealant (Seal-Rite). The average roughness (R a,
      MUm) of the specimens was measured with a profilometer (Surtronic 10 Tylor
      Hobson). Surface hardness was determined by utilizing Vicker's surface hardness
      (VHN) with a Micromet II Microhardness tester. Each specimen acted as its own
      control. Data were analyzed with 2-way analysis of variance (ANOVA), and mean
      values were compared with independent t-test. All analyses were performed with
      the SPSS program version 16 (USA). Differences with a P-value of ?0.05 were
      considered statistically significant. RESULTS: Comparison of enamel surfaces
      before and after application of resin infiltrant revealed no significant
      differences in surface hardness; however, enamel surfaces treated by infiltrant
      showed significantly higher VHN (244.0 +/- 79.8) values than those treated with
      fissure sealant (37.5 +/- 14.2). Surface roughness did not differ before and
      after application of either material to sound enamel. Enamel surfaces treated
      with fissure sealant (5.3 +/- 1.4) were significantly smoother than those treated
      with infiltrant (6.9 +/- 2.0). CONCLUSION: Within the limitations of the study,
      the results showed that enamels treated with the resin infiltrant showed
      approximately the same microhardness and surface roughness as sound enamel,
      indicating that this material might be suitable for the treatment of enamel
      subsurface lesions.

PMID- 23960534
TI  - Color change of some aesthetic dental materials: Effect of immersion solutions
      and finishing of their surfaces.
AB  - OBJECTIVES: The purpose of this research was to evaluate the color change of five
      aesthetic dental materials, before and after immersion in distilled water and
      blue food color solution for 7 and 21 days, and to study the effect of finishing
      the surfaces on any color change. METHODS: Disc shaped samples of five types of
      light curing composite (A2) (n = 10 samples/composite) were prepared and all
      samples were light-cured with a Plasma Arc light cure unit for ten seconds. One
      side of each sample disc was finished and polished with a Super-Snap system all
      samples. After 24 h, color measurements of each sample were conducted using a
      digital spectrophotometer. Five sample discs from each composite group were
      immersed in 30 ml of food color solution for 7 and 21 days, while the remaining
      five sample discs were immersed in 30 ml of distilled water as a control. Color
      measurements were repeated for all samples at 7 and 21 days after immersion. The
      color changes were statistically analyzed using t-tests within the same group. A
      result was considered statistically significant at alpha = 0.05. RESULTS: The
      color differences (DeltaE) ranged from 0.4 to 4.66 and statistically significant
      differences on the finished and unfinished surfaces were observed after immersion
      in the food color solution for 7 days. No significant differences were found in
      any group after immersion in the food color solution for 21 days. The Tetric
      EvoCeram and Arabesk groups showed less color differences after 7 and 21 days
      than other composites. CONCLUSION: Finished composite surfaces showed less
      coloration than unfinished surfaces after 7 days, but all surfaces (finished and
      unfinished) were highly colored for all composite types after 21 days.

PMID- 23960535
TI  - Characterization of heat emission of light-curing units.
AB  - OBJECTIVES: This study was designed to analyze the heat emissions produced by
      light-curing units (LCUs) of different intensities during their operation. The
      null hypothesis was that the tested LCUs would show no differences in their
      temperature rises. METHODS: FIVE COMMERCIALLY AVAILABLE LCUS WERE TESTED: a
      "Flipo" plasma arc, "Cromalux 100" quartz-tungsten-halogen, "L.E. Demetron 1"
      second-generation light-emitting diode (LED), and "Blue Phase C5" and "UltraLume
      5" third-generation LED LCUs. The intensity of each LCU was measured with two
      radiometers. The temperature rise due to illumination was registered with a type
      K thermocouple, which was connected to a computer-based data acquisition system.
      Temperature changes were recorded in continues 10 and 20 s intervals up to 300 s.
      RESULTS: The Flipo (ARC) light source revealed the highest mean heat emission
      while the L.E. Demetron 1 LED showing the lowest mean value at 10 and 20 s
      exposure times. Moreover, Cromalux (QTH) recorded the second highest value for
      all intervals (12.71, 14.63, 14.60) of heat emission than Blue Phase C5 (LED)
      (12.25, 13.87, 13.69), interestingly at 20 s illumination for all intervals the
      highest results (18.15, 19.27, 20.31) were also recorded with Flipo (PAC) LCU,
      and the lowest (6.71, 5.97, 5.55) with L.E. Demetron 1 LED, while Blue Phase C5
      (LED) recorded the second highest value at the 1st and 2nd 20 s intervals (14.12,
      11.84, 10.18) of heat emission than Cromalux (QTH) (12.26, 11.43, 10.26). The
      speed of temperature or heat rise during the 10 and 20 s depends on light
      intensity of emitted light. However, the QTH LCU was investigated resulted in a
      higher temperature rise than LED curing units of the same power density.
      CONCLUSION: The PAC curing unit induced a significantly higher heat emission and
      temperature increase in all periods, and data were statistically different than
      the other tested groups (p < .05). LED (Blue Phase C5) was not statistically
      significant (p < .05) (at 10 s) than QTH units, also LED (Blue Phase C5,
      UltraLume 5) generates obvious heat emission and temperature rises than QTH units
      (at 20 s) except for those which have lower power density of LED curing units
      (first generation). Thus, the null hypothesis was rejected.

PMID- 23960536
TI  - Female sex hormones and periodontal health-awareness among gynecologists - A
      questionnaire survey.
AB  - Sex hormones play an important role in periodontal health and disease. For
      example, puberty, menses, pregnancy, menopause, and oral contraceptive use
      influence a woman's periodontal health. Periodontal infection has also been
      associated with adverse pregnancy outcomes. Subsequently, it is important that
      gynecologists are educated about hormonal effects on women's oral health. The
      current study assessed gynecologist's awareness regarding the effect of female
      sex hormones on periodontal health, preterm delivery, and maternal periodontal
      disease. METHODS: Gynecologists from the Bagalkot district of the Karnataka
      state, India, completed a questionnaire regarding female hormonal and periodontal
      health. Respondents were divided into two groups: Group A (doctors that practiced
      at a medical college or hospital) and Group B (doctors that practiced at private
      hospitals). Out of 73 gynecologists, 62 (85%) completed the survey, with 19
      (30.6%) participants in Group A and 43 (69.4%) participants in Group B. Survey
      responses were collected in the presence of the investigator, and data between
      the groups were statistically compared. RESULTS: Our findings showed that most
      gynecologists were aware and concerned about female patient's oral health during
      various hormonal phases. However, gynecologists practicing at medical colleges
      and hospitals (Group A) had significantly greater health awareness than doctors
      practicing at private hospitals (Group B). CONCLUSION: Women have special
      periodontal health care considerations, and there is a need for better oral
      health education among caregivers. Our results suggest that increasing dental
      health awareness among gynecologists would significantly improve women's health
      and pregnancy outcomes.

PMID- 23960537
TI  - Simple removable appliances to correct anterior and posterior crossbite in mixed
      dentition: Case report.
AB  - Different techniques have been used to correct anterior and posterior crossbites
      in mixed dentition. This case report illustrates the treatment of anterior and
      unilateral posterior crossbites during the mixed dentition. The patient was a 9
      year-old boy with a crossbite of the maxillary right permanent central incisor
      and a unilateral right posterior crossbite, both expressed by a functional shift
      in the sagittal and transverse dimensions. Two upper acrylic removable
      appliances, each with an expansion jackscrew, were used to correct the
      crossbites. The total active treatment time was 4 months; the treatment outcomes
      were successfully maintained for the subsequent 4 months. General and pediatric
      dentists, as well as orthodontists, may find this technique useful in managing
      crossbite cases of the mixed dentition and utilizing the discussion and
      illustrations for further clinical guidance. 

PMID- 23960538
TI  - Tongue pearl: A novel technique for treatment of an infant with median facial
      cleft and microcephaly.
AB  - This case report illustrates the presurgical treatment of a patient having a
      median facial cleft and microcephaly, using a guidance appliance. The appliance
      was custom designed and modified with a pearl-like acrylic structure attached to
      its lingual surface for pushing the extremely protruded tongue back to its normal
      position to facilitate anesthesia and surgical lip closure. Total treatment time
      was 5 weeks. Regaining normal tongue position, in turn, facilitated both
      intubation and extubation, preventing the postoperative respiratory distress the
      authors had experienced with similar cases. 

PMID- 23960539
TI  - Plagiarism reporting: My experience.

PMID- 23960540
TI  - A paradigm shift in the diagnosis & management of dentofacial deformities.

PMID- 23960541
TI  - Effect of exposure time on the accuracy and reliability of cone beam computed
      tomography in the assessment of dental implant site dimensions in dry skulls.
AB  - OBJECTIVES: To investigate the accuracy and reliability of implant site
      measurements, recorded from low-dose cone beam computed tomography (CBCT) images.
      METHODS: CBCT reformatted images of five skulls were obtained using 40, 20 and 7
      s exposure protocols. From these protocols, edentulous ridge dimensions were
      recorded by two observers and compared with measurements recorded directly from
      the bone. The measurement errors and intra- and inter-examiner reliability were
      calculated for each exposure protocol and compared with each other. RESULTS: The
      mean absolute errors from the 40, 20 and 7 s protocols were 0.50, 0.46, and 0.51
      mm, respectively. The intra-examiner reliability scores were 0.996, 0.995 and
      0.998, respectively. The inter-examiner reliability scores were 0.993, 0.998 and
      0.994, respectively. There was no significant difference in accuracy or
      reliability between the three protocols. CONCLUSIONS: In imaging of dry skulls,
      lowering the CBCT exposure time from 40 s to 20 or 7 s does not affect the
      reliability or accuracy of implant site measurements.

PMID- 23960542
TI  - Comparison of craniofacial morphology, head posture and hyoid bone position with
      different breathing patterns.
AB  - OBJECTIVES: The aim of this study was to evaluate differences in craniofacial
      morphology, head posture and hyoid bone position between mouth breathing (MB) and
      nasal breathing (NB) patients. METHODS: Mouth breathing patients comprised 34
      skeletal Class I subjects with a mean age of 12.8 +/- 1.5 years (range: 12.0-15.2
      years). Thirty-two subjects with skeletal Class I relationship were included in
      the NB group (mean 13.5 +/- 1.3 years; range: 12.2-14.8 years). Twenty-seven
      measurements (15 angular and 12 linear) were used for the craniofacial analysis.
      Additionally, 12 measurements were evaluated for head posture (eight
      measurements) and hyoid bone position (four measurements). Student's t-test was
      used for the statistical analysis. Probability values <0.05 were accepted as
      significant. RESULTS: Statistical comparisons showed that sagittal measurements
      including SNA (p < 0.01), ANB (p < 0.01), A to N perp (p < 0.05), convexity (p <
      0.05), IMPA (p < 0.05) and overbite (p < 0.05) measurements were found to be
      lower in MB patients compared to NB. Vertical measurements including SN-MP (p <
      0.01) and PP-GoGn (p < 0.01), S-N (p <0.05) and anterior facial height (p < 0.05)
      were significantly higher in MB patients, while the odontoid proses and palatal
      plane angle (OPT-PP) was greater and true vertical line and palatal plane angle
      (Vert-PP) was smaller in MB patients compared to NB group (p < 0.05 for both). No
      statistically significant differences were found regarding the hyoid bone
      position between both groups. CONCLUSIONS: The maxilla was more retrognathic in
      MB patients. Additionally, the palatal plane had a posterior rotation in MB
      patients. However, no significant differences were found in the hyoid bone
      position between MB and NB patients.

PMID- 23960543
TI  - Treatment of symptomatic oral lichen planus (OLP) with 0.1% tacrolimus powder in
      Oraguard-B - A pilot prospective study.
AB  - OBJECTIVES: The purpose of this study was to investigate the efficacy and safety
      of 0.1% tacrolimus powder in Oraguard-B for the treatment of patients with
      symptomatic oral lichen planus (OLP). METHODS: This was a nonrandomized,
      nonblinded study conducted in the outpatient department. The 20 patients with
      symptomatic OLP oral lichen planus who were asked to participate in the study
      were provided with 20-g containers of the study medication. Patients were asked
      to use the medication over the symptomatic areas three times a day until
      resolution of the lesion. Patients were recalled to assess the drug response
      every 15 days. RESULTS: The duration of treatment ranged from 30 to 183 days,
      with a mean of 81.8 +/- 44.4 days; all 20 patients reported a favourable response
      to the topical tacrolimus therapy. Eleven patients had complete resolution of
      their lesions. In 16 of 20 patients, there was marked resolution in symptoms as
      recorded by visual analogue scale. Out of 10 patients followed up for a period of
      3 months, 5 had recurrence of their lesions but with less intensity, and the
      patients were symptomless. No serious side effects were associated with the study
      medication. CONCLUSION: Topical tacrolimus 0.1% in Oraguard-B was effective and
      safe in treating patients with OLP. However, there is still a need to undertake
      more detailed and objective clinical studies to determine the exact benefit of
      tacrolimus compared with conventional therapies and examine the influence of
      different dose regimes and formulations and assess the incidence of recurrence.

PMID- 23960544
TI  - Prevalence of apical periodontitis and quality of root canal treatment in an
      adult Palestinian sub-population.
AB  - PURPOSE: The aim of this study was to determine the prevalence of apical
      periodontitis and the technical quality of root canal fillings in a Palestinian
      sub-population. METHODS: The panoramic radiographs of 258 patients (142 females,
      116 males) attending dental clinics in 2010 were examined to identify the
      presence of apical lesions associated with any remaining teeth, excluding third
      molars. The technical quality of root canal fillings was also evaluated by
      assessing apical extension from the radiographic apex. The panoramic radiographs
      were taken by a well-trained radiology assistant and evaluated by a radiologist
      and an endodontist. Statistical analysis was performed with the chi-square test
      with a significant level set at P < 0.05%. RESULTS: Of 6482 teeth examined
      radiographically, 978 (15.1%) had radiographic signs of apical periodontitis
      (AP). The prevalence of AP was 8.3% in teeth without filled roots and 59.5%
      (509/855) in root canal-treated teeth. The prevalence of AP and endodontic
      treatment increased with age and differed significantly (p < 0.05) between males
      and females. The majority (74.5%) of root canal fillings was performed
      inadequately, and most (77.2%) inadequate fillings were >2 mm short of the
      radiographic apex. The presence of AP was correlated significantly with poorly
      executed root canal fillings (p < 0.05). CONCLUSIONS: The present study found a
      high prevalence and incidence of AP in association with root-filled teeth. The
      technical quality of many root canal treatments was unacceptable.

PMID- 23960545
TI  - Effect of gravity and capillarity on human saliva penetration in coronally
      unsealed obturated root canals.
AB  - AIM: The purpose of this study was to evaluate the effect of gravity and
      capillarity on penetration of human salivary bacteria into the entire length of
      obturated root canals, and to demonstrate the dye penetration configuration.
      MATERIALS AND METHODS: Fifty single-rooted premolars were decoronated, prepared
      to a standardized length of 15 mm, instrumented, and randomly divided into two
      groups (A and B) of 25 teeth each. Each group consisted of experimental (15
      samples) and negative and positive controls (five samples each). The experimental
      groups were obturated with gutta-percha and root canal sealer. The positive
      control groups were obturated with a single cone of gutta-percha and root canal
      sealer. The outer surfaces (except for the apical 2 mm) were covered with two
      layers of nail varnish. An apparatus containing Brain Heart Infusion broth was
      designed, in which the teeth were placed. The samples in Group A were placed
      upside down, while Group B was placed normally. The coronal portions of the
      samples were placed in contact with fresh saliva. The number of days required for
      bacteria to penetrate the entire length of canals was determined. The samples
      were then immersed in India ink to determine the dye penetration configuration.
      Data were analyzed using Student's t-test. RESULTS: The extent of dye penetration
      was significantly greater in Group B compared to Group A, and they were in a
      pattern rather than linear form. CONCLUSIONS: Gravity and capillarity
      insignificantly affected bacterial leakage. Although gravity and capillarity did
      not affect bacterial penetration when applied to the coronal access of
      endodontically treated teeth, it seems that they can promote penetration of India
      ink into the canal after the bacterial test on the same tooth.

PMID- 23960546
TI  - Evaluation of light-curing units in rural and urban areas.
AB  - OBJECTIVES: To evaluate the distribution of light-curing units (LCU) used in an
      urban area (Riyadh) and a rural area (Kharj) of Saudi Arabia, and to compare
      their irradiance values. METHODS: The study involved three dental centers in
      urban areas and two in rural areas, all of which were parts of a single
      healthcare institution providing dental services. The light outputs (power mW)
      from 140 LCUs were measured by laboratory-grade spectrometry, and the irradiance
      (mW/cm(2)) was calculated from the tip area of each LCU. The minimum acceptable
      irradiance outputs for the quartz-tungsten-halogen (QTH) and light-emitting diode
      (LED) units were set at 300 and 600 mW/cm(2), respectively. The ages of these
      units and the protocol used to light-cure the resins were also determined.
      RESULTS: The total number of LCUs was 140, 112 (78%) in urban areas, and 28 (22%)
      in rural areas. In rural areas, only 7 of the 22 (32%) QTH units delivered
      irradiances greater than 300 mW/cm(2) and were therefore considered clinically
      acceptable, whereas 4 of the 6 (66.7%) LED units delivered values greater than
      600 mW/cm(2). In urban centers, 43 of 61 (70.5%) LED units and 25 of 61 (49%) QTH
      units were considered clinically acceptable. Irradiance values for both QTH (P <
      0.01) and LED (P < 0.05) units were significantly better in urban than in rural
      areas. CONCLUSIONS: Urban areas had a greater distribution of LCUs than rural
      areas. Overall, irradiance values were significantly higher in urban areas.

PMID- 23960547
TI  - Comparison between a laser fluorescence device and visual examination in the
      detection of occlusal caries in children.
AB  - Occlusal surfaces of molars are especially susceptible to the development of
      caries due to the features, such as pits and deep fissures, of their anatomical
      structure. AIM: To evaluate the efficiency of DIAGNOdent laser fluorescence
      measurements in comparison with visual examination for occlusal caries detection
      for first permanent molars in children. METHODS: The study involved 156 permanent
      molar teeth in 40 children aged 7-12 years. A relatively new technology, the
      fluorescence laser DIAGNOdent pen, was used for detecting and diagnosing caries
      on the occlusal surfaces of molars. The visual examination of fissures was based
      on the Ekstrand classification system. RESULTS: The results showed a strong
      relationship between examination with the DIAGNOdent and visual inspection.
      DIAGNOdent's sensitivity and specificity were 97% and 52%, respectively,
      indicating that the laser fluorescence DIAGNOdent pen is a reproducible and
      accurate diagnostic tool that may be very helpful in conjunction with visual
      examination in the detection of occlusal caries in permanent molars in children.

PMID- 23960548
TI  - The impact of technology on dental education.

PMID- 23960549
TI  - A systematic review of population-based dental caries studies among children in
      Saudi Arabia.
AB  - OBJECTIVE: Dental caries critically impacts the health and development of
      children. Understanding caries experience is an important task for Saudi Arabian
      policymakers to identify intervention targets and improve oral health. The
      purpose of this review is to analyze current data to assess the nationwide
      prevalence and severity of caries in children, to identify gaps in baseline
      information, and to determine areas for future research. METHODS: A search of
      published and unpublished studies in PubMed, Google, and local Saudi medical and
      dental journals was conducted for the three keywords "dental," "caries," and
      "Saudi Arabia." The inclusion criteria required that the articles were population
      based studies that assessed the prevalence of dental caries in healthy children
      attending regular schools using a cross-sectional study design of a random
      sample. RESULTS/DISCUSSION: The review was comprised of one unpublished thesis
      and 27 published surveys of childhood caries in Saudi Arabia. The earliest study
      was published in 1988 and the most recent was published in 2010. There is a lack
      of representative data on the prevalence of dental caries among the whole Saudi
      Arabian population. The national prevalence of dental caries and its severity in
      children in Saudi Arabia was estimated to be approximately 80% for the primary
      dentition with a mean dmft of 5.0 and approximately 70% for children's permanent
      dentition with a mean DMFT score of 3.5. The current estimates indicate that the
      World Health Organization (WHO) 2000 goals are still unmet for Saudi Arabian
      children. CONCLUSION: Childhood dental caries is a serious dental public health
      problem that warrants the immediate attention of the government and the dental
      profession officials in Saudi Arabia. Baseline data on oral health and a good
      understanding of dental caries determinants are necessary for setting appropriate
      oral health goals. Without the ability to describe the current situation, it is
      not possible to identify whether progress is being made toward these goals. A
      roadmap with a clear starting point, destination, and pathway is a desperately
      needed tool to improve the oral health of Saudi Arabian children.

PMID- 23960550
TI  - Perception of Saudi dentists and lay people to altered smile esthetics.
AB  - AIM: To evaluate and compare the perceptions of Saudi dentists and lay people to
      altered smile features. METHODS: Thirty-six digital smile photographs with
      altered features were used. Altered features included the following: crown
      length, width, gingival level of the lateral incisors, gingival display, midline
      diastema, and upper midline shift. The photographs were presented to a sample of
      30 dentists and 30 lay people with equal gender distribution. Each participant
      rated each picture with a visual analogue scale, which ranged from 0 (very
      unattractive) to 100 (very attractive). RESULTS: Dentists were more critical than
      lay people when evaluating symmetrical crown length discrepancies. Compared to
      lay people, Saudi dentists gave lower ratings to a crown length discrepancy of >2
      mm (P < 0.001), crown width discrepancy of ?2 mm (P < 0.05), change in gingiva to
      lip distance of ?2 mm (P < 0.01), and midline deviation of >1 mm (P < 0.01).
      There was no significant difference between dentists and lay people towards
      alterations in the gingival level of the lateral incisors or towards a space
      between the central incisors. No significant sex difference was seen across the
      groups. CONCLUSION: In this sample, Saudi dentists gave significantly lower
      attractiveness scores to crown length and crown width discrepancies, midline
      deviations, and changes in gingiva to lip distance compared to Saudi lay people.

PMID- 23960551
TI  - Effect of low pull headgear on head position.
AB  - OBJECTIVE: To evaluate changes in head position following the use of low pull
      headgear (LHG) and compare these changes with an untreated control group.
      SUBJECTS AND METHODS: The test group comprised pre-treatment and post-treatment
      lateral cephalograms of 30 males, aged 11 +/- 1.5 years, who were receiving LHG
      therapy for correction of Class II malocclusion. Pre-observation and post
      observation lateral cephalograms of 25 untreated male subjects, aged 11 +/- 1.6
      years, served as controls. The average treatment time for the treatment group was
      12 +/- 2.02 months and the average observation period for the control group was
      11 +/- 1.03 months. Four postural variables (NSL/CVT, NSL/OPT, CVT/HOR, OPT/HOR)
      were measured to evaluate the head position in all subjects pre- and post
      observations. RESULTS: There was no significant difference in all the
      measurements concerning the head position within each group (p > 0.05). The mean
      differences of pre- and post-observations of 4 postural variables in the LHG
      group were 1.43, 0.9, -1.13, and -1.08, while those of the control group were
      1.56, -0.32, -0.24, and 0.04, respectively. There was no significant difference
      between the headgear and control groups for any of the postural variables
      measured (p = 0.924, 0.338, 0.448, and 0.398, respectively). CONCLUSIONS:
      Although postural variables showed considerable variability in both groups, head
      position exhibited no significant changes over a period of 11-12 months either in
      the control or headgear group.

PMID- 23960552
TI  - Effect of different tetra pack juices on microhardness of direct tooth colored
      restorative materials.
AB  - PURPOSE: To examine the effect of apple and orange juices on the surface hardness
      of direct tooth-colored restorative materials. MATERIALS AND METHODS: The
      materials included resin-modified glass ionomer cement (Vitremer 3MTM ESPETM Core
      buildup restorative) and composite resin (FiltekTM 3MTM ESPETM Z350). A total of
      45 disks of each restorative material were prepared. The disks were divided into
      groups of 15, which were immersed for 7 days in deionized water (G1/G4, control
      group), apple juice (G2/G5), or orange juice (G3/G6). The pH of the apple juice
      was approximately 4.8 and the pH of the orange juice was approximately 4.9.
      Surface hardness tests were performed before immersion and at various times
      following immersion. Statistical analysis included two-way ANOVA with repeated
      measurement and Tukey's test. RESULTS: Exposure to juices significantly reduced
      the hardness of both materials (p < 0.05), while deionized water did not affect
      the surface hardness of either material. The ionomer cement experienced a greater
      reduction than the composite resin (p = 0.000). There was no significant
      difference in the effect of apple and orange juices. CONCLUSION: Juice box-type
      fruit juices reduced the hardness of direct tooth-colored restorative materials.
      Material selection should be considered when planning restorations in patients
      who have experienced tooth surface loss. In terms of the materials evaluated in
      this study, the composite material provides greater durability under acidic
      conditions.

PMID- 23960553
TI  - Patterns and etiology of maxillofacial fractures in Riyadh City, Saudi Arabia.
AB  - OBJECTIVE: The aim of the present study was to study the etiologies and patterns
      of maxillofacial fractures in patients treated in Riyadh City, Saudi Arabia,
      between 2007 and 2011. PATIENTS AND METHODS: Data were obtained through a
      retrospective review of 237 patients admitted to the King Saud Medical City
      Dental Department with a diagnosis of maxillofacial trauma. After excluding
      patient files with incomplete or unclear records, and cases in which computed
      tomography showed no evidence of fracture, the files of 200 patients with a
      diagnosis of maxillofacial fracture were included in the study. For each case,
      patient's sex and age, pattern of facial fractures, and cause of injury were
      recorded on a data sheet. The data were transferred to an SPSS (ver. 16.0; SPSS
      Inc., Chicago, IL, USA) spreadsheet for statistical analysis. The chi-square test
      was used to test the association between two categorical variables or factors
      (age group, cause) with p value set at p<0.05, and t-test value at <0.05 and
      independent. RESULTS: Motor vehicle accidents were the most common cause of
      maxillofacial fractures in most age groups, especially in males. Within the study
      sample, mandibular fractures were significantly more common than middle-third
      facial fractures (56.4% vs. 43.6%; p=0.006). Among mandibular fractures,
      parasymphyseal fractures were most common (47%), followed by condylar fractures
      (35.3%). Most (77.2%) middle-third facial fractures involved the zygomatic
      complex, and the incidence of such fractures differed significantly between male
      and female patients. p=0.72, not significant. CONCLUSION: Males were more prone
      to maxillofacial fractures, perhaps as a result of the conservative nature of
      Saudi society, as the rules of Saudi Arabia do not allow the females to drive.
      Motor vehicle accidents were the most common cause of maxillofacial fractures in
      patients aged 10-29 years, indicating the high demand for the application of
      stricter traffic rules to reduce the rate of such accidents.

PMID- 23960554
TI  - An indirect technique for assuring simplicity and marginal integrity of
      provisional restorations during full mouth rehabilitation.
AB  - Full mouth rehabilitation with fixed prosthodontics can be a time- and labor
      intensive process. The use of provisional restorations allows the treating
      clinician to determine the functional and esthetic requirements of the definitive
      prostheses. However, in the case of full mouth rehabilitation, the individual
      preparation of provisional restorations for multiple teeth may complicate the
      provisional phase and increase the treatment time. This article describes a
      method to simplify the indirect fabrication of provisional restorations for full
      mouth reconstruction. Provisional restorations may be easily achieved by
      splinting the provisional restorations in sextants, trimming them according to
      red pencil marks around the prepared margins as guidelines, and fitting them in
      the laboratory, utilizing a second set of solid casts for the prepared teeth. 

PMID- 23960555
TI  - Recurrent lip swelling as a late presentation of Kawasaki disease: Case report
      and review of literature.
AB  - Kawasaki Disease (KD) is an acute systemic vasculitis of unknown etiology. In
      many developed countries, KD has replaced rheumatic heart disease as the leading
      cause of acquired heart disease in children. Among the classical criteria for a
      diagnosis of KD are oral manifestations such as strawberry tongue, erythematous
      cracked lip, and oropharyngeal mucositis. We report the case of a 24-year-old
      Saudi female with a history of Kawasaki disease who presented to our oral
      medicine clinic with recurrent painless swelling of the upper lip. As lip
      swelling has not previously been reported as an oral manifestation of KD, this
      case represents a novel presentation of recurrent Kawasaki disease in an adult
      female. 

PMID- 23960556
TI  - Nanorobots: Future in dentistry.
AB  - The purpose of this paper is to review the phenomenon of nanotechnology as it
      might apply to dentistry as a new field called nanodentistry. Treatment
      possibilities might include the application of nanotechnology to local
      anesthesia, dentition renaturalization, the permanent cure for hypersensitivity,
      complete orthodontic realignment in a single visit, covalently bonded diamondized
      enamel, and continuous oral health maintenance using mechanical dentifrobots.
      Dental nanorobots could be constructed to destroy caries-causing bacteria or to
      repair tooth blemishes where decay has set in, by using a computer to direct
      these tiny workers in their tasks. Dental nanorobots might be programed to use
      specific motility mechanisms to crawl or swim through human tissue with
      navigational precision, to acquire energy, to sense and manipulate their
      surroundings, to achieve safe cytopenetration, and to use any of a multitude of
      techniques to monitor, interrupt, or alter nerve-impulse traffic in individual
      nerve cells in real time. 

PMID- 23960557
TI  - Stud attachments for the mandibular implant-retained overdentures: Prosthetic
      complications. A literature review.
AB  - A plethora of attachment systems for mandibular two-implant overdentures is
      currently available often without evidence-based support. Technical aspects are
      now parameters considered when choosing the appropriate attachment. Despite the
      increasing use of the Locator attachments, studies regarding their properties
      remain scarce. Peer reviewed articles published in English up to 2011, were
      identified through a MEDLINE search (Pubmed and Elsevier) and a hand search of
      relevant textbooks and annual publications. Emphasis was made on the technical
      complications as well as the loss of retention related to the attachments in
      implant-retained overdentures, primarily the Locator attachment. The evaluation
      of the long-term outcome of implant overdentures and complications associated
      with different attachment systems may provide useful guidelines for the clinician
      in selecting the type of attachment system and overdenture design. 

PMID- 23960558
TI  - Professional attitudes and behaviors acquired during undergraduate education in
      the College of Dentistry, King Saud University.
AB  - OBJECTIVES: The purpose of the study was to investigate and evaluate the
      professional attitudes and behaviors acquired by students and recently graduated
      dentists during undergraduate education at King Saud University. METHODS: This
      cross-sectional survey used a 27-item questionnaire covering four cumulative
      theoretical dimensions of professionalism. Questionnaires were distributed to
      fifth-year students, interns, and demonstrators in the College of Dentistry
      during the academic year 2010-2011, and 203 completed questionnaires were used in
      analyses. Descriptive statistics were used to summarize responses. Crosstab and
      chi-squared tests were used, with statistical significance set at P < 0.05.
      RESULTS: The response rate was 79.3% (43.6% of males, 94% of females). Eighty
      seven questionnaires were collected from fifth-year students, 92 from interns,
      and 24 from demonstrators. Many (59%) participants demonstrated high levels of
      professional attitudes and behaviors, whereas 40% did not comply with the
      elements of professionalism. Analyses revealed highly significant differences in
      certain responses with regard to gender, academic level, and grade point average.
      CONCLUSIONS: Although some participants did not possess all professional
      qualities, all participants possessed at least some elements of professionalism
      measured in this study. We thus recommend a strategic effort to develop targeted
      plans emphasizing professionalism at all levels of the dental school curriculum.
      High-profile role modeling, lectures, seminars, and academic ceremonies are ways
      of achieving professional development among dental students in parallel with
      their acquisition of basic scientific knowledge and clinical skills. This
      approach will formally and informally communicate that professionalism is a core
      value.

PMID- 23960559
TI  - Expression of human beta defensins (HBDs) 1, 2 and 3 in gingival crevicular fluid
      of patients affected by localized aggressive periodontitis.
AB  - AIM: To study the effect of nonsurgical periodontal therapy on the expression
      frequencies of human beta-defensin (HBD)-1, -2, and -3 in the gingival crevicular
      fluid (GCF) of patients affected by localized aggressive periodontitis. MATERIALS
      AND METHODS: Twenty patients affected by localized aggressive periodontitis (age
      range, 20-35 years) and 20 healthy subjects (age range, 21-37 years) were
      examined with clinical periodontal parameters and radiographic examination with
      the long-cone parallel technique. All periodontitis patients underwent
      nonsurgical periodontal therapy combined with doxycycline treatment and a
      maintenance program (including brushing with regular toothpaste). GCF samples
      were collected from patients and healthy control subjects at baseline as well as
      3 months after periodontal therapy for the patient group. RESULTS: In the patient
      group, the expression frequencies of HBD-1, -2, and -3 mRNA at baseline were 30%,
      85%, and 35%, respectively, which changed after periodontal therapy to 80%, 45%,
      and 85%, respectively (all P < 0.001). In the healthy control subjects, the
      expression frequencies were 95%, 40%, and 95% for HBD-1, -2, and -3,
      respectively, which were different from those of diseased patients at baseline
      (all P < 0.001). CONCLUSIONS: The appropriate expression of HBD peptides in
      health and disease may contribute to the maintenance of periodontal homeostasis,
      possibly through its antimicrobial effects and the promotion of adaptive immune
      responses.

PMID- 23960560
TI  - Minimally invasive use of coloured composite resin in aesthetic restoration of
      periodontially involved teeth: Case report.
AB  - Gingival recession causes not only aesthetic problems, but problems with oral
      hygiene, plaque accumulation, speech, and tooth sensitivity. Replacing the
      missing gingival tissue with composite resin, when indicated, can be a time- and
      cost-effective solution. Here we report the case of a 25-year-old female who
      presented with generalized gingival recession. Black triangles were present
      between the maxillary and mandibular anterior teeth due to loss of interdental
      tissues, caused by recent periodontal surgery. She also had slightly malposed
      maxillary anterior teeth. The patient elected to replace gingival tissue with
      pink composite resin and to alter the midline with composite resin veneers. The
      first treatment phase involved placement of pink gingival composite to restore
      the appearance of interdental papilla to her upper (16, 15, 14, 13, 12, 11, 21,
      22, 23, and 24) and lower (34, 33, 32, 31, 41, 42, 43, and 44) teeth. Phase two
      was to place direct composite resin bonded veneers on her upper (16, 15, 14, 13,
      12, 11, 21, 22, 23, and 24) teeth to alter the midline and achieve desired
      colour. The third treatment phase was to level the lower incisal edge shape by
      enameloplasty (31, 32, 41, and 42) to produce a more youthful and attractive
      smile. This case report and brief review attempt to describe the clinical
      obstacles and the current treatment options along with a suggested protocol. Use
      of contemporary materials such as gingival coloured composite to restore lost
      gingival tissue and improve aesthetics can be a simple and cost-effective way to
      manage patients affected by generalized aggressive periodontitis (AgP). 

PMID- 23960561
TI  - Oral manifestations of lipoid proteinosis: A case report and literature review.
AB  - Lipoid proteinosis is an uncommon autosomal recessive metabolic disorder that
      presents in early life with hoarseness and pox-like acneiform scars involving the
      skin and mucous membranes. Previous studies have attributed the prevalence of
      lipoid proteinosis to consanguineous parents. This paper reports a classical case
      of lipoid proteinosis with oral manifestations but without a history of
      consanguinity. 

PMID- 23960562
TI  - Breaking the barriers.

PMID- 23960563
TI  - Editorial.

PMID- 23960564
TI  - A resuscitation "dilemma" theory-practice-ethics. Is there a theory-practice
      ethics gap?
AB  - The theory-practice-ethics gap - a new paradigm to contemplate. Practices based
      on tradition, rituals and outdated information are placed into a nonscientific
      paradigm called the theory-practice gap. Within this paradigm there is often a
      gap between theoretical knowledge and its application in practice. This theory
      practice gap has always existed [Allmark, P., 1995. A classical view of the
      theory-practice gap in nursing. J. Adv. Nurs. 22 (1), 18-23; Hewison, A. et al.,
      1996. The theory-practice gap in nursing: a new dimension. J. Adv. Nurs. 24 (4),
      754-761]. Its creation is often sited as a culmination of theory being idealistic
      and impractical, even if practical and beneficial, are often ignored. Most of the
      evidence relating to the non integration of theory and practice makes the
      assumption that environmental factors are responsible and will affect learning
      and practice outcomes, hence the "gap". In fact, it is the author's belief, that
      to "bridge the gap" between theory and practice an additional component is
      required, called ethics. A moral duty and obligation ensuring theory and practice
      integrate. In order to effectively implement new practices, one must deem these
      practices are worthy and relevant to their role as healthcare providers.
      Otherwise, we fall victims to providing nothing more than a lip service. This
      introduces a new concept which the author refers to as the theory-practice-ethics
      gap. This theory-practice-ethics gap must be considered when reviewing some of
      the unacceptable outcomes in health care practice. The author believes that there
      is a crisis of ethics where theory and practice integrate, and as a consequence,
      malfeasance. We are failing to fulfill our duty as healthcare providers and as
      patient advocates. One practice of major concern, which the author will endeavor
      to unfold relates to adult and pediatric resuscitation. 

PMID- 23960565
TI  - Mechanical ventilation strategy following Glenn and Fontan surgeries: On going
      challenge!
AB  - The Glenn and Fontan operations put the pulmonary and systemic circulations in
      series. It has been shown that positive pressure ventilation (PPV) decreases
      pulmonary blood flow (PBF) and cardiac output (CO), and negative pressure
      ventilation (NPV) significantly improves PBF and CO. If early extubation is not
      achievable, the postoperative ventilator management strategy should aim at
      promoting PBF and CO by lowering pulmonary vascular resistance (PVR) and
      intrathoracic pressure. Multiple ventilator strategies have been evaluated to
      optimize this physiology, including high frequency ventilation, hyperventilation
      post Glenn, hypoventilation post Glenn with buffered pH, and the use of inhaled
      nitric oxide as an adjunct therapy for mechanical ventilation. In this review,
      the results of these studies will be reviewed and discussed. 

PMID- 23960566
TI  - Inhibition of Na(+)-H(+) exchange before resuscitation following hemorrhagic
      shock is cardioprotective in rats.
AB  - BACKGROUND: Stimulation of the Na(+)-H(+) exchanger during resuscitation
      following hemorrhagic shock results in myocardial injury and dysfunction.
      Inhibition of the Na(+)-H(+) exchanger appears to be a new pharmacological tool
      for myocardial protection following ischemia-reperfusion. Our lab showed that
      inhibition of the Na(+)-H(+) exchanger, using amiloride and dimethyl amiloride,
      before ex vivo resuscitation of isolated perfused hearts protected the myocardium
      and improved the post-resuscitation myocardial function. The purpose of the
      present study was to examine the myocardial protective effects of treating the
      hemorrhagic shocked rats by intra-arterial injection of 20 MUM dimethyl amiloride
      (DMA), a specific Na(+)-H(+) exchanger blocker, before in vivo resuscitation.
      METHODS: Sprague-Dawley rats were assigned to hemorrhagic treated or untreated
      groups (n = 4 per group). After 60 min of hemorrhagic shock, rats were treated or
      not by injection of 20 MUM 5-(N,N-dimethyl)-amiloride (DMA) intra-arterially.
      Rats were then resuscitated in vivo and monitored for 30 min. Then hearts were
      harvested and perfused in the Langendorff system for 60 min for measurements of
      hemodynamic function. RESULTS: Administration of DMA before in vivo resuscitation
      following 60 min of hemorrhagic shock and 30 min of in vivo resuscitation, 20 MUM
      DMA intra-arterially significantly improved post-resuscitation myocardial
      function. CONCLUSION: Our results suggest that DMA protects the heart against
      post-resuscitation myocardial injury.

PMID- 23960567
TI  - Pacing for hypertrophic obstructive cardiomyopathy does it work?
AB  - Sixty-nine years old lady presented with sudden cardiac arrest, she was found to
      have hypertrophic obstructive cardiomyopathy, she refused septal myomectomy and
      had a dual chamber ICD implanted, she was put on right ventricular apical pacing
      with short AV interval, after pacing her max pressure gradient across left
      ventricular out flow tract (LVOT) dropped from 117 mmHg to 21 mmHg and her
      symptoms much improved over a follow up period of 1 year. 

PMID- 23960568
TI  - Smoking in Saudi Arabia and its relation to coronary artery disease.
AB  - OBJECTIVES: The health hazards related to smoking are well known. Smoking is a
      recognized risk factor for coronary artery disease (CAD). Despite rejection of
      smoking by the Saudi community, we are still seeing smokers in our population.
      This study is designed to determine the prevalence of smoking in the Kingdom of
      Saudi Arabia (KSA), and to find out its relation to CAD. This study is part of
      the Coronary Artery Disease In Saudis (CADIS) study. METHODS: This health survey
      was conducted by collecting data regarding smoking status among adult Saudis aged
      between 30 and 70 years of both sexes in KSA over a five year period from 1995 up
      to 2000. The study sample was of normal distribution and representative of all
      regions of KSA. The data were analyzed to provide the prevalence of smoking and
      its relation with CAD. RESULTS: The total number of subjects was 17,350, and
      current smokers were 2217; accordingly the overall prevalence of smoking among
      Saudis was 12.8%. Males (1555) were significantly smoking more than females (662)
      with a prevalence of 18.7% and 7.3%, respectively (P < 0.0001). Smoking is more
      prevalent among Saudis living in urban, northern, western, and eastern regions
      compared to other regions of KSA. Smokers are more likely to develop CAD compared
      to non-smokers (P < 0.0001). CONCLUSIONS: Smoking is a prevalent health problem
      among Saudis that requires intervention for eradication. We found clear
      association between cigarettes smoking and CAD particularly among males.
      Persistent education of the health hazards related to smoking is recommended
      particularly at early age in-order to prevent initiation of smoking.

PMID- 23960569
TI  - The utilization of multidetector computerized tomographic angiography in the
      evaluation of double aortic arch.

PMID- 23960570
TI  - International guidelines: Adoption or adaptation by the Saudi Heart Association?

PMID- 23960571
TI  - Treatment options for transposition of the great arteries with ventricular septal
      defect complicated by pulmonary vascular obstructive disease.
AB  - The arterial switch operation is the procedure of choice for patients with
      isolated transposition of the great arteries or those with associated atrial
      and/or ventricular septal defects. After the development of pulmonary arterial
      hypertension, the surgical options for patients with a late presentation include
      either retraining the left ventricle by pulmonary artery banding followed by an
      arterial switch operation or palliative atrial or arterial switch, with or
      without medical management of pulmonary hypertension. We present a case with D
      transposition of the great arteries with ventricular septal defects and
      irreversible pulmonary arterial hypertension who improved after a palliative
      atrial switch operation. 

PMID- 23960572
TI  - Ventricular noncompaction: Over or under diagnosis?
AB  - Ventricular noncompaction (VNC) describes a cardiomyopathy characterized by
      excessive myocardial trabeculations and deep intertrabecular recesses. Detection
      rates are increasingly rising and the frequency of NVC has changed from a disease
      that is thought to be rare to that described as 'relatively common'. However,
      there had been a number of un-answered questions regarding the clinical and
      echocardiographic features of VNC. In this review we discuss the frequency of VNC
      and emphasize its distinctive clinical features and associations. 

PMID- 23960573
TI  - Changes in the saudi heart journal.

PMID- 23960574
TI  - Integrated cardiac imaging in 2009 and beyond.

PMID- 23960576
TI  - Routine leaflet augmentation of left atrioventricular valve in the repair of
      atrioventricular septal defect.
AB  - INTRODUCTION: A better understanding of the morphology of complete
      atrioventricular septal defects (CAVSD) has impacted on surgical techniques and
      results. On some occasions the leaflet tissue is deficient and repair becomes
      difficult which leads to atrioventricular valve (AVV) regurgitation following the
      surgical repair of the AVSD. OBJECTIVES: This study was conducted to evaluate a
      modified technique in which two patches where used to close the complete
      atrioventricular septal defect (CAVSD) with augmentation of the left
      atrioventricular valve (AVV) with the ventricular septal defect (VSD) patch.
      METHODS: The technique was performed on 105 infants with CAVSD at a mean age of
      11.7 +/- 23 months (median 5.7, range 1-135). Both superior and inferior bridging
      leaflets are divided routinely to expose the VSD. An autologous pericardial
      patch, sized precisely, is sutured to the ventricular septum. A 3-4 mm of extra
      patch is fashioned beyond the plane of the annulus and sutured to the divided
      leaflet of the left AVV. A second autologous pericardial atrial patch is attached
      to the body of the VSD patch at the plane of the annulus allowing 3-4 mm of the
      VSD patch to augment the left AV valve. RESULTS: There was one early death among
      these infants. At early postoperative echo all infants had no significant
      residual lesions. The contribution of the patch-augmented left AV valve to
      competency is clearly seen by two-dimensional echocardiography. At a mean follow
      up of 27 +/- 10 months there were two late deaths with normal last
      echocardiography. There were only two children who progressed to severe left AV
      valve regurgitation needing reoperations. CONCLUSIONS: This modified technique
      yields good anatomical repair. Allowing reconstruction of both AV valves
      independent of the other and is in particular helpful in cases of deficient left
      AVV tissue.

PMID- 23960575
TI  - Off-pump coronary revascularization: A potential benefit for female patients?
AB  - Coronary artery disease is one of the leading causes of illness for both men and
      women. However, women are 3 times more likely to die for coronary artery disease
      as they are of breast cancer. There are an increasing prevalence of coronary
      artery disease in women and thus facing the need for surgical revascularization.
      It has long being accepted that women carry a high risk of coronary surgery than
      men. Many investigators have suggested that female itself is predictive of poor
      outcome after on pump coronary surgery. We thought to search the litlature to
      investigate whether women who undergo off-pump surgery receive any benefits
      compared with women undergoing on-pump surgery. 

PMID- 23960577
TI  - The pattern of acute rheumatic fever in children: Experience at the children's
      hospital, Riyadh, Saudi Arabia.
AB  - BACKGROUND: The study was carried out in Riyadh City Hospital to determine the
      hospital prevalence of acute rheumatic fever (ARF), its characteristics and to
      determine the proportion of the ARF population that have recurrent attacks.
      METHODS: The study was an analysis of 83 children with ARF, admitted to the
      Children's Hospital, Riyadh, over a 10-year period (1994-2003). The diagnosis of
      ARF was based on clinical features as defined in the modified Jones criteria with
      evidence of recent streptococcal infection. The diagnosis of recurrence of
      rheumatic fever in children with rheumatic heart disease was based on the
      presence of one major criterion apart from carditis or two minor criteria, in
      addition to evidence of preceding streptococcal infection. RESULTS: The mean age
      at presentation was 9 years. In 31 (37%) cases, arthritis was the only major
      Jones criterion. In 30 (36%) others, arthritis was associated with carditis and
      in 3 (4%), with chorea. Cardiac involvement was documented in 44 (53%) cases; it
      occurred alone in 5 (6%), with arthritis in 30 (36%), and with chorea in 9 (11%)
      others. Among the 44 with carditis, the pattern of cardiac involvement was
      valvular only (mild carditis) in 30 (68%), while it was severe in the remaining
      14 (32%) cases who also had heart failure. The involvement of the mitral valve
      alone occurred in 26 (59%) cases in the form mitral regurgitation, while both
      aortic and mitral valve regurgitation were present in 11 (25%) cases, and aortic
      valve regurgitation alone in four (9%) others. Chorea was the only major
      criterion of ARF in 5 children (6%), while it occurred in association with other
      major criteria in 12 (15%) others. Nineteen (23%) children had recurrent attacks
      of ARF. CONCLUSION: ARF continues to occur in Saudi Arabia in the period (1994
      2003), despite the progress made in the socio-economic development of the
      country, and this is often associated with severe cardiac involvement.

PMID- 23960578
TI  - Recurrent supraventricular tachycardias prevalence and pathophysiology after RF
      ablation: A 5-year registry.
AB  - BACKGROUND: The introduction of technique of radiofrequency (RF) catheter
      ablation in 1990, has revolutionized management of different types of paroxysmal
      supraventricular tachycardia (PSVT). In spite of higher success rate, there were
      reported recurrences among different types of SVT. The aim of this study was to
      report the efficacy of RF ablation, its complications, recurrence rate and its
      predictors. METHODS: The material of this study (our 3rd registry) included
      patients who underwent electrophysiological study (EPS) and radiofrequency
      ablation of their supraventricular tachycardia in the past 5 years, starting from
      January 2002 to January 2007 at The Critical Care Medicine Department, Cairo
      University. RESULTS: Out of 400 pts studied, 381 (95%) had been subjected to
      radiofrequency ablation (RF) ablation while the remaining 19 pts (4.7%) refused
      ablation for fear of possible complications. Out of the 381 pts, 366 (96%) had
      their target tachycardia successfully terminated, from them 26 pts (7%)
      experienced recurrence after having successful RF ablation. Nine pts (34.6%) of
      total recurrence was reported in pts with AVNRT, 7 pts (26.9%) of total
      recurrence was reported in pts with AVRT utilizing septal accessory pathway (Rt
      AS and /or Rt PS AP), 4 pts (15.4%) was reported in pts with double AP, 2 pts
      (7.7%) of total recurrence was reported in pts with AFl, one pt (3.8%) of total
      recurrence was reported in cases of AT. Redo ablation have been carried out
      successfully in 25 pts (96.2%), and one pt (3.8%) refused ablation for fear of
      possible complications. CONCLUSIONS: Although electrophysiological study and RF
      ablation eliminated different types of SVT. However, there may be increased
      incidence of recurrence among pts with AVNRT and AVRT utilizing concealed septal
      AP and multiple APs secondary to the complexity of AVN physiology, the critical
      location of septal AP, the clinical expertise, and poor electrophysiological
      criteria for good procedural success.

PMID- 23960579
TI  - Optimizing door-to-balloon times for STEMI interventions - Results from the
      SINCERE database.
AB  - BACKGROUND: Primary angioplasty decreases mortality and improves long-term
      outcomes for patients with STEMI. To be most effective, it needs to be performed
      expediently, with door-to-balloon times (D2B) less than 90 min. METHODS: From
      January 2005 to presently, 420 short D2B STEMI interventions were performed at 5
      community hospitals by a single experienced operator creating the SINCERE (Single
      INdividual Community Experience REgistry) database. RESULTS: Median D2B time was
      78 min, median procedure time (local anesthesia to recanalization) was 13 min;
      85.2% of procedures had D2B time <90 min; 95% of the procedures were successful -
      relief of chest pain, >70% ST segment resolution, TIMI 3 flow and Myocardial
      Perfusion Grade 3. CONCLUSIONS: Primary PCI with high success rates and
      predictable short D2B times can be performed with standardized techniques in
      community hospitals.

PMID- 23960581
TI  - The role of 3D transesophageal echocardiography during percutaneous closure of
      atrial septal defect.

PMID- 23960580
TI  - Persistent fifth aortic arch diagnosed by echocardiography and confirmed by
      angiography: Case report and literature review.
AB  - Persistent fifth aortic arch is a rare congenital anomaly that can be discovered
      incidentally or at postmortem exam. It can be associated with major congenital
      heart malformations involving the systemic or the pulmonary circuits. It usually
      has no clinical significance but can be either, beneficial as in systemic outflow
      tract obstructions or cause hemodynamic compromise when associated with a
      significant left to right shunt. We report an infant with persistent fifth aortic
      arch associated with Shone's complex diagnosed accurately by transthoracic
      echocardiography and confirmed by cardiac catheterization and computed
      tomography. 

PMID- 23960582
TI  - Cardiac imaging integration in 2009 and beyond.

PMID- 23960583
TI  - Cardiac Imaging Integration in 2009 and Beyond: Cardiovascular magnetic
      resonance.
AB  - Cardiovascular magnetic resonance (CMR) is currently well recognized in clinical
      practice for the diagnosis and management of cardiovascular diseases. CMR is
      helpful in the diagnosis and prognosis of patients with myocardial infarction.
      The high spatial resolution of CMR enables accurate assessment of tissue
      characterization in various types of cardiomyopathy. In addition, CMR may play a
      complementary role with echocardiography in clinical evaluation of patients with
      valvular and congenital heart disease. 

PMID- 23960584
TI  - Developments in hybrid scanning.

PMID- 23960585
TI  - Dutch national screening and disease management program for Familial
      Hypercholesterolemia (FH) - A model for Saudi Arabia?

PMID- 23960586
TI  - Effect of oral ibuprofen on patent ductus arteriosus in premature newborns.
AB  - BACKGROUND AIM OF THE STUDY: Patent ductus arteriosus (PDA), a common finding
      among premature infants, is conventionally treated by intravenous indomethacin.
      Intravenous ibuprofen was recently shown to be as effective and to have fewer
      adverse reactions in preterm infants. If equally effective, then oral ibuprofen
      for PDA closure would have several important advantages over the intravenous
      route. This study was designed to determine whether oral ibuprofen treatment is
      efficacious and safe in closure of a PDA in premature infants. PATIENTS AND
      METHODS: Thirty-three premature group I (study group) were treated with ibuprofen
      10 mg/kg administered through a feeding tube. Thirty-three premature group II
      (control group) receive placebo the two imaging procedures were again performed
      24 h after each ibuprofen dose. When the PDA was still hemodynamically
      significant, as demonstrated by echocardiography, and there was no evidence of
      deterioration in brain ultrasonography, a second dose of ibuprofen 5 mg/kg
      (placebo for control) was administered. A third equivalent dose was given after
      another 24 h if necessary. Cranial ultrasound was repeated 1 week after the last
      ibuprofen dose and again before discharge from the ward. Hematochemical analysis
      was preformed daily in the unit during the first days of life. RESULTS: In the
      study group the rate of PDA closure was 93.9% (31 of 33 cases) while in the
      control group the rate of PDA closure was 30.3% (10 of 33 cases) with significant
      difference in between. There was no reopening of the ductus after closure had
      been achieved. No infant required surgical ligation of the ductus in study group
      while in the control group 24.2% (8 of 33 cases) were required surgical ligation
      (Table 2). Twenty-one newborns were treated with 1 dose of ibuprofen, 9 were
      treated with 2 doses, and the remaining 3 were treated with 3 doses. CONCLUSION:
      Oral ibuprofen is an effective and safe alternative to intravenous ibuprofen for
      PDA closure in premature infants.

PMID- 23960587
TI  - Early echocardiography abnormalities in obese children and adolescent and
      reversibility of these abnormalities after significant weight reduction.
AB  - BACKGROUND: Obesity is becoming an epidemic threat for the individual and
      society. The increasing prevalence of overweight children and adolescents is
      likely to have a great impact on the future cardiovascular health of these
      subjects. Obesity is a strong risk factor for cardiovascular morbidity and
      mortality. Cardiac abnormalities of obese children and adolescents include the
      echocardiographically revealed early and preclinical LV or septal hypertrophy,
      and left or right ventricular dysfunction. Most of these abnormalities, which are
      usually more pronounced in patients with morbid obesity, can be partially
      reversed after weight reduction. AIM OF THE STUDY: Evaluate early
      echocardiography changes in obese children and whether these cardiac
      abnormalities reverse with significant weight reduction in children and
      adolescents or not. METHODS: We started this study by 50 obese children and
      adolescents and 30 non obese controls matched for age and sex. BMI was
      calculated. Complete echocardiographic study was performed on each patient and
      control subject. Hematological and biochemical variables were determined in the
      obese subjects from fasting blood samples and included glucose, total
      cholesterol, triglycerides (TG), HDL cholesterol and LDL cholesterol. All our
      patients' strict dietetic regime with exercises for 6 months. After 6 months full
      examination, including all measurements and echocardiography and laboratory
      investigations were done again. RESULTS: Obese children has abnormalities of left
      ventricle structure and function (consisting of increased left ventricular wall
      dimensions and mass and alteration of diastolic function) that can be detected by
      echocardiography. Furthermore, (parameters of lipid metabolism) were found to be
      independent predictors of adverse LV remodeling and of diastolic dysfunction. As
      well as this study provides evidence that abnormalities of left ventricular wall
      dimension and mass in obese children and adolescents can improve with significant
      weight reduction. CONCLUSION: This study has demonstrated that young, obese
      children and adolescents have early significant changes in left ventricular wall
      dimensions and early diastolic filling compared with non obese and this changes
      are reversible with weight reduction.

PMID- 23960588
TI  - Hyperuricemia and its association with carotid intima-media thickness in
      hypertensive and non hypertensive patients.
AB  - Carotid intima-media thickness (C-IMT) measured noninvasively by ultrasonography
      is widely used as a marker for increased risk of cardiovascular disease. Also
      hyperuricemia (HU) is a well recognized risk factor for cardiovascular diseases.
      The study was designed to assess the relation between hyperuricemia and carotid
      intima-media thickness C-IMT in patients with and without hypertension (HTN).
      This study included 126 patients divided into four groups: (1) Group A, included
      59 hypertensive patients with hyperuricemia. (2) Group B, included 29
      hypertensive patients without hyperuricemia. (3) Group C, included 17 patients
      with hyperuricemia and normal blood pressure without history of hypertension. (4)
      Group D, included 21 control subjects. We measured carotid intima-media thickness
      by B-mode ultrasound in the common carotid and internal carotid artery. Routine
      echocardiography and uric acid level was assessed for all patients. We found that
      C-IMT was significantly higher in group A, B and C than group D; and it was
      significantly higher in group A than B. This means that C-IMT is significantly
      higher in all hypertensive groups than control group but it was significantly
      higher in hypertensive hyperuricemia (group A) than those hypertensives without
      hyperuricemia. We also observed a higher C-IMT in hyperuricemic non hypertensive
      patients than control group this means that hyperuricemia per se could be a risk
      factor for atherosclerosis. Uric acid levels among the whole number of patients
      included in the study and among the groups with hyperuricemia (group A and C)
      were positively correlated with the intimal-media thickness (IMT) while there
      were no correlations in the other two groups without hyperuricemia. We found that
      left ventricular hypertrophy (LVH) was significantly higher in hypertensive
      patients (group A&B) than normotensives (group C&D) either with or without
      hyperuricemia and this was evident in the hypertensive hyperuricemic patients
      (group A); but unexpectedly we observed the presence of LVH in the hyperuricemic
      non hypertensive patients (group C) which was significantly higher than the
      control group (group D). This means that hyperuricemia is a risk factor for
      development of LVH hypertrophy independently of hypertension. Therefore, higher
      serum uric acid levels are associated with increased C-IMT and left ventricular
      hypertrophy in hypertensive and even non hypertensive patients. So, early
      screening for hyperuricemia and lowering serum uric acid levels might be
      beneficial in slowing progression of atherogenesis. 

PMID- 23960590
TI  - Message from the President of the SHA.

PMID- 23960591
TI  - The current state of risk stratification and EuroSCORE in cardiac surgery.

PMID- 23960589
TI  - Prevalence and clinical significance of heart murmurs detected in routine
      neonatal examination.
AB  - OBJECTIVE: To determine the prevalence and clinical impact of murmurs detected
      during routine physical examination in neonates. METHODS: In a 4 years
      retrospective study, 6333 healthy newborn babies were screened for the presence
      of a heart murmur during routine neonatal physical examination. Prematures or
      those who were admitted to neonatal intensive care unit or any neonate with a
      risk factor that is known to be associated with increased incidence of congenital
      heart disease were excluded from the study. All those with murmurs underwent
      echocardiography examination and color Doppler study. RESULTS: Murmurs were
      detected in 87 neonate (1.37%) of whom 37 (42.5%) had a structural cardiac
      malformation. Ventricular septal defect (62%) was the most common diagnosis,
      followed by atrial septal defect, pulmonary stenosis and patent ductus
      arteriosus. CONCLUSION: The prevalence of heart murmur was 13.7 per 1000 neonate.
      If a murmur is heard there is a (42.5%) chance of their being underlying
      structural defects. Therefore, detection of a murmur should prompt early referral
      for investigation and diagnosis or appropriate family reassurance.

PMID- 23960592
TI  - Lessons from the SYNTAX trial.
AB  - Despite the fact that CABG is the standard of care for patients with multivessel
      coronary arteries and/or left main stem stenosis, PCI has become a rival to CABG
      in patients with multivessel coronary artery disease or left main disease.
      However, the need for repeat revascularization, in-stent stenosis and thrombosis
      remain the achilis heal of PCI. SYNTAX trial randomized patients with left main
      disease and/or three-vessel disease to PCI with TAXus stent or CABG with the
      concept that PCI is not inferior to CABG. At 1 and 2 years follow up, MACCE was
      significantly increased in PCI patients mainly attributed to increased rate of
      repeat revascularization; however, stroke was significantly more with CABG. The
      composite safety endpoint of death/stroke/MI was comparable between the 2 groups.
      Therefore the criterion for non-inferiority was not met. What we learn from
      SYNTAX is that multi disciplinary team approach should be the standard of care
      when recommending treatment in more complex coronary artery disease. SYNTAX makes
      interventionists and surgeons come together, it may set the benchmark for MVD
      revascularization. PCI and CABG should be considered complementary rather than
      competitive revascularization strategies. There is no substitute for sound
      clinical judgment that takes into account the patient's overall clinical profile,
      functionality, co-morbidities, as well as the patient's coronary anatomy. The
      SYNTAX Score should be utilized to decide on treatment of patients with LM/MVD.
      Patients with low and intermediate score can be treated with PCI or CABG with
      equal results. Those with high score do better with CABG. SYNTAX trial showed
      that 66% of patients with 3VD or LMD are still best treated with CABG. In the
      remaining 1/3 of patients with low syntax score, PCI may be considered as an
      alternative to surgery. Finally, medical treatment should be optimized in
      patients going for CABG. 

PMID- 23960593
TI  - Coronary insufficiency in children: Review of literature and report of a rare
      case with unknown aetiology.
AB  - Myocardial ischemia due to coronary artery disease is a rare condition in
      children. The reported causes of this condition include vasculitis; commonest
      being Kawasaki' disease, pre-mature atherosclerosis due to familial
      dyslipidemias, congenital coronary artery anomalies and post-operative
      complications of procedures requiring coronary artery re-implantation in
      children, e.g. arterial switch procedure and Ross procedure. Allograft
      arteriopathy after heart transplantation is a more recent addition to this list
      (Mavroudis et al., 1996). Surgical procedures required for the treatment of
      coronary artery disease in children include, but are not limited to coronary
      artery re-implantation, re-routing, augmentation of the osteum, and coronary
      artery bypass grafting (CABG). We present our experience of a rare case of triple
      vessel coronary artery disease of unknown aetiology in a child, treated with
      coronary artery bypass grafting procedure. 

PMID- 23960594
TI  - Gender differences in the surgical management and early clinical outcome of
      coronary artery disease: Single centre experience.
AB  - OBJECTIVE: To investigate the gender disparity in the distribution of patient
      related risk factors and their effect on the surgical management and clinical
      outcome of coronary artery disease in Saudi population. MATERIALS AND METHODS: We
      carried out a retrospective analysis of prospectively collected data of 971
      patients undergoing isolated coronary artery bypass grafting (CABG) at our
      institution between January 2005 and December 2008. Seven hundred and eighty
      seven patients (81%) were males and 184 patients (19%) were females. We analyzed
      gender-based difference in clinical presentation and patient-related pre
      operative risk factors and studied their impact on surgical management and
      clinical outcome. RESULTS: The mean age was 59.5 years in males and 63.4 years in
      females (p = <0.0001). Associated co-morbidities were higher in females.
      Prevalence of diabetes mellitus was 61.2% in males and 78.8% in females (p-value
      = <0.0001); hypertension 61.9% in males and 79.9% in females (p-value <0.0001);
      hyperlipidemia 66.7% in males and 77.7% in females (p-value 0.0035); morbid
      obesity 24.7% in males and 45.1% in females (p-value <0.0001); and Hypothyroidism
      2.5% in males and 13.6% in females (p-value <0.0001). Smoking was the only risk
      factor with higher prevalence in males compared to females (44.2% v/s 2.2%; p
      value <0.0001). The mean logistic euroSCORE was 3.94 in males and 5.51 in females
      (p < 0.0003). On-pump and off-pump CABG was carried out in equal numbers in two
      groups. Females required urgent surgery and less than 3 grafts more frequently
      while males underwent elective surgery and more than 3 grafts in greater numbers.
      No significant difference was present between the two gender groups in aortic
      occlusion times and bypass times. Univariant analysis revealed females gender as
      an independent risk factor for higher in-hospital mortality (1.1% versus 4.9% p =
      0.0026) and higher incidence of post-operative complications like surgical wound
      infection, need for prolonged ventilation, low cardiac output state and multi
      organ failure (p-values 0.01 or less). CONCLUSION: Female gender is an
      independent predictor of adverse outcome after isolated CABG due to significantly
      higher co-morbidities and acute presentation and independent of their peri
      operative management. Therefore, major socioeconomic education and preventive
      measures are needed to reduce the burden of major co-morbidities in females and
      to seek early cardiac advice and care.

PMID- 23960595
TI  - Early outcome of tetralogy of Fallot repair in the current era of management.
AB  - BACKGROUND: Traditional use of trans-annular patch (TAP) to release right
      ventricular outflow tract (RVOT) obstruction during tetralogy of Fallot (TOF)
      repair may lead to a harmful pulmonary regurgitation. Different approaches have
      been used to release RVOT obstruction and spare the pulmonary valve (PV)
      function. In this study, we aim to evaluate the post-operative course of patients
      who had TOF repair in the current era that emphasizes on protective strategy of
      releasing RVOT obstruction and preserving PV function. METHODS: A retrospective
      study of all TOF cases repaired in our institute between March 2002 and December
      2007 was conducted. Cases were classified into two groups; group I included
      patients that had a TAP, while group II included cases that had simple TOF repair
      without TAP. Group I was subdivided into two groups, group (A) which include
      patients who had TAP without a valve. Group (B) includes those who had TAP with a
      monocuspid valve (Contegra). We compared post-operative care and outcome of all
      groups. RESULTS: Eighty-three patients fulfilled the study criteria. There were
      64 cases (77%) in group I, and 19 cases (23%) in group II. All children tolerated
      surgical repair and did well. We observed no statistically significant difference
      in the post-operative ICU care, complications rates and morbidity between all
      groups. There was no surgical mortality in all groups. CONCLUSION: Children
      undergoing TOF repair had excellent short-term outcome with the current
      protective strategy aiming to spare valvular function, and conserving myocardial
      function. Applying a monocuspid patch technique did not show clear short-term
      benefits. Long term follow up is needed to evaluate future difference in
      different techniques.

PMID- 23960596
TI  - Dextrocardia, aortopulmonary window with transposition of the great arteries,
      case report.
AB  - Transposition of the great arteries (D-TGA) in combination with aortopulmonary
      window (APW) is a very rare entity and carries high morbidity and mortality. Only
      few cases have been reported with this association. We report the first case of D
      TGA and APW with mirror image dextrocardia which was repaired successfully. 

PMID- 23960597
TI  - Transcatheter closure of patent ductus arteriosus in infantile form of Scimitar
      syndrome with a type II Amplatzer Ductal Occluder.
AB  - We report a unique case of infantile form of Scimitar syndrome with a patent
      ductus arteriosus and pulmonary hypertension. The PDA was closed percutaneously
      using the new Amplatzer Ductal Occluder device type II. 

PMID- 23960598
TI  - Left lateral imaging position in routine myocardial perfusion practice.
AB  - Left lateral position in myocardial perfusion imaging has been described in the
      literature to reduce the incidence of diaphragmatic attenuation artifact,
      therefore improving the specificity of the test. 

PMID- 23960599
TI  - The basics of echocardiography.
AB  - Cardiac echocardiography is becoming an essential diagnostic tool for a variety
      of cardiac pathology. Acquiring the necessary knowledge will help non cardiac and
      the cardiac specialist to understand the echocardiography images and reports and
      in return will improve the care of the patients. The aim of these of publication
      is to address the basic knowledge of cardiac echocardiography and the recent
      advances of its applications. 

PMID- 23960601
TI  - Message from the president of saudi heart association.

PMID- 23960600
TI  - Health technology assessment (HTA) in cardiac field.

PMID- 23960602
TI  - The current status of percutaneous mitral valve repair.

PMID- 23960603
TI  - Moderate ischemic mitral regurgitation: Is there a case for early intervention?
AB  - Ischemic mitral regurgitation (IMR) results from left ventricular remodelling
      after myocardial infarction and severely affects cardiovascular mortality and
      morbidity. Ischemic mitral valve regurgitation also represents a negative
      prognostic factor for long-term survival in patients undergoing surgical
      myocardial revascularization. While severe mitral regurgitation should always be
      corrected during a coronary artery bypass operation, the decision making is more
      difficult in patients with a moderate degree of regurgitation. In this review, we
      wish to highlight the negative impact of IMR on long-term survival and discuss
      the available evidence for surgical correction of IMR at the time of coronary
      revascularization. 

PMID- 23960604
TI  - Current challenges and future directions in cardiac imaging.
AB  - Imaging is one of the most important accomplishments of medicine during the last
      1000 years. The contribution of modern imaging to progress in the delivery of
      health care is unquestioned. However, we need to refine our use of imaging,
      limiting its use to those occasions when it can contribute directly or indirectly
      to improving and lengthening the lives of patients. Technology prowess in imaging
      alone is not sufficient to deliver value to individuals or to society. Continued
      investment in imaging technology requires critical appraisal of its use in
      clinical decision making and patient outcomes. 

PMID- 23960606
TI  - Cardiotoxicity with adjuvant trastuzumab use in breast cancer: A single
      institution's experience.
AB  - BACKGROUND: Trastuzumab use in Her-2-neu positive breast cancer patients is the
      current standard of care. Trastuzumab is known to result in cardiotoxicity. The
      toxicity seems to be dose-dependent, and serial cardiology assessment with
      echocardiography is advised. In spite of this, patients do develop cardiotoxicity
      and identification of patients at high risk and, if possible, any preventive
      means is of paramount importance. METHODS: We performed a retrospective analysis
      of medical records of all breast cancer patients presenting at King Khalid
      University Hospital from 02/2006 to 06/2009 and receiving adjuvant trastuzumab on
      the basis of either immunohistochemistry showing Her-2-neu (3+) or FISH positive
      Her-2-neu receptor status. Patients received adjuvant trastuzumab at an 8 mg/kg
      loading dose over 90 min, followed by 6 mg/kg every 3 weeks. A repeat multigated
      acquisition scan/echocardiogram was done after every 4 courses. Patient
      characteristics, such as age, menopausal status, tumor size, lymph nodal status,
      distant metastasis at presentation, grade of tumor, estrogen and progesterone
      receptor status, comorbid conditions (diabetes, hypertension, ischemic heart
      diseases), chemotherapy received, total dose of trastuzumab, timing of
      cardiotoxicity, and number of patients having cardiotoxicity, were recorded. A
      patient was said to have cardiotoxicity if the ejection fraction dropped by 10%
      of the original value or if there was a drop in the ejection fraction below the
      normal value. RESULTS: A total number of 98 breast cancer patient records were
      analyzed in this study. A total of 11 patients developed cardiotoxicity, evident
      by a drop in the ejection fraction on an echocardiogram. Seven patients out of 11
      had a drop in ejection fraction below 10% of the baseline value, and 4 patients
      out of 11 had a drop in ejection fraction below normal values. A total of 5
      patients became symptomatic with dyspnea on exertion, with 2 being of NYC Class
      I, 2 being of NYC Class II, 1 being of NYC Class III, and none being of NYC Class
      IV. Seven patients out of 11 with cardiotoxicity had diabetes and hypertension as
      comorbid conditions. Patients receiving doxorubicin in neoadjuvant and adjuvant
      settings were associated with cardiotoxicity. The total dose of trastuzumab had a
      strong association, with the patient getting more than 60 mg/kg in a 3-weekly
      fashion being associated with cardiotoxicity. CONCLUSIONS: Trastuzumab is
      associated with significant cardiotoxicity. Asymptomatic and symptomatic
      cardiotoxicity and toxicity seem to be dose-dependent in an adjuvant setting. At
      the end of therapy, more frequent than usual monitoring of cardiac function is
      suggested to prevent this toxicity.

PMID- 23960605
TI  - Mitral balloon valvuloplasty.
AB  - Percutaneous mitral balloon valvuloplasty (MBV) was introduced in 1984 by Inoue
      who developed the procedure as a logical extension of surgical closed
      commissurotomy. Since then, MBV has emerged as the treatment of choice for severe
      pliable rheumatic mitral stenosis (MS). With increasing experience and better
      selection of patient, the immediate results of the procedure have improved and
      the rate of complications declined. When the reported complications of MBV are
      viewed in aggregate, complications occur at approximately the following rates:
      mortality (0-0.5%), cerebral accident (1-2%), mitral regurgitation (MR) requiring
      surgery (1.6-3%). These complication rates compare favorably to those reported
      after surgical commissurotomy. Several randomized trials reported similar
      hemodynamic results with MBV and surgical commissurotomy. Restenosis after MBV
      ranges from 4% to 70% depending on the patient selection, valve morphology, and
      duration of follow-up. Restenosis was encountered in 31% of the author's series
      at mean follow-up 9 +/- 5.2 years (range 1.5-19 years) and the 10, 15, and 19
      years restenosis-free survival rates were (78 +/- 2%) (52 +/- 3%) and (26 +/-
      4%), respectively, and were significantly higher for patients with favorable
      mitral morphology (MES ? 8) at 88 +/- 2%, 67 +/- 4% and 40 +/- 6%), respectively
      (P < 0.0001). The 10, 15, and 19 years event-free survival rates were (88 +/- 2%,
      60 +/- 4% and 28 +/- 7%, respectively, and were significantly higher for patients
      with favorable mitral morphology (92 +/- 2%, 70 +/- 4% and 42 +/- 7%,
      respectively (P < 0.0001). The effect of MBV on severe pulmonary hypertension,
      concomitant severe tricuspid regurgitation, left ventricular function, left
      atrial size, and atrial fibrillation are addressed in this review. In addition,
      the application of MBV in specific clinical situations such as in children,
      during pregnancy and for restenosis is discussed. 

PMID- 23960607
TI  - Paediatric cardiology programs in countries with limited resources: how to bridge
      the gap.
AB  - Establishing paediatric cardiology service in a country with limited resources
      like Sudan is a challenging task. A paediatric cardiac team was formed then the
      services in different disciplines were gradually established. Echocardiography
      (echo) clinics were founded in tertiary and peripheral hospitals. Cardiac
      catheterization (cath) was established at the Sudan Heart Centre (SHC) in 2004
      and over 400 procedures had been performed including interventional
      catheterization like pulmonary valve dilatation, patent ductus arteriosus and
      atrial septal defect device closure. Congenital heart surgery started in 2001,
      currently 200 cases are done each year including closed procedures as well as
      open heart procedures for patients weighing more than 8 kg. Cardiology-cardiac
      surgery as well as adult congenital heart disease meetings were held and
      contributed positively to the services. The cardiology-cardiac surgery scientific
      club meeting was founded as a forum for academic discussions. A fellowship
      program was established in 2004 and included seven candidates trained in
      paediatric cardiology and intensive care. Two training courses had been
      established: congenital heart disease echo and paediatric electrocardiogram
      interpretation. Links with regional and international cardiac centres had
      important roles in consolidating our program. Significant obstacles face our
      service due to the small number of trained personnel, high cost of procedures,
      the lack of regular supplies and lack of cardiac intensive care facilities for
      young infants. Bridging the huge gap needs extensive official as well as non
      governmental efforts, training more staff, supporting families and collaboration
      with regional and international centres. 

PMID- 23960608
TI  - Libman-Sacks endocarditis with an unusual presentation.
AB  - Systemic lupus erythematosus is relatively common medical disorder with female
      predominance. This disorder can affect any organ system. Cardiac involvement is
      variable which can include pericardium, myocardium and endocardium. The
      endocardial involvement commonly affects mitral and aortic valves. This report
      discusses lupus endocarditis in young man with atypical presentation. 

PMID- 23960609
TI  - Acute myocardial infarction associated with acute gouty arthritis.
AB  - The association of hyperuricemia with increased risk of atherosclerosis has been
      reported in previous studies but the link of acute gouty arthritis, hyperuricemia
      and acute myocardial infarction (MI) is not seen frequently. Here we report a 33
      year old male who presented with hyperuricemia, acute gouty arthritis and acute
      myocardial infarction. Hyperuricemia contributed not only to accelerated
      atherosclerosis but might be blamed for promoting environment for acute
      myocardial infarction. 

PMID- 23960611
TI  - What practicing cardiologists need to know about radiation exposure in cath. Lab?

PMID- 23960610
TI  - After more than 300 defibrillation shocks, patient still alive 12 years later
      refractory torsade de pointes due to polypharmacy and persistent vomiting.
AB  - Acquired torsade de pointes ventricular tachycardia (TdP) is a rare but serious
      life-threatening arrhythmia caused by an array of cardiac and non-cardiac drugs.
      It is often refractory to pharmacological therapy and may result in death or
      require frequent defibrillations. In our case study a young female patient with
      no underlying heart disease developed very frequent sustained TdP requiring
      frequent defibrillations without which she would have certainly died. The
      ventricular arrhythmia in this patient was of multifactorial origin - cisapride,
      drug-drug interaction and persistent vomiting resulting in electrolyte
      disturbance and malnutrition. The patient survived after more than 300
      defibrillation shocks over a period of 5 days and she is still alive 12 years
      later. 

PMID- 23960612
TI  - Diagnosis of coronary artery anomalies using multidetector CT angiography.

PMID- 23960613
TI  - The use of nuclear imaging to assess the myocardial viability.

PMID- 23960614
TI  - Understanding and expressing "Risk".

PMID- 23960615
TI  - Echocardiography of the mitral valve.
AB  - Mitral valve disease is the second most common valvular heart disease after the
      aortic valve worldwide. Mitral valve has historically been a structure of
      interest by pioneers in echocardiography. One of the earliest applications of
      echocardiography was in the diagnosis of valvular heart disease, particularly
      mitral stenosis. In this review we wish to take the reader through the structural
      and hemodynamic evaluation of the normal mitral valve. 

PMID- 23960616
TI  - Sha 21.

PMID- 23960617
TI  - Message from the president.

PMID- 23960618
TI  - Three dimensional imaging using 64 detector row multi-slice CT should be used
      more widely for the diagnosis and management of congenital heart disease.

PMID- 23960619
TI  - Apico-Aortic Conduit for severe aortic stenosis: Technique, applications, and
      systematic review.
AB  - Patients referred for aortic valve replacement are often elderly and may have
      increased surgical risk associated with ascending aortic calcification, left
      ventricular dysfunction, presence of coronary artery disease, previous surgery,
      and/or presence of several co-morbidities. Some of these patients may not be
      considered candidates for conventional surgery because of their high risk
      profile. While transcatheter aortic valve replacement constitutes a widely
      accepted alternative, some patients may not be eligible for this modality due to
      anatomic factors. Apico-Aortic Conduit (AAC) insertion (aortic valve bypass
      surgery) constitutes a possible option in those patients. Apico-Aortic Conduit is
      not a new technique, as it has been used for decades in both pediatric and adult
      populations. However, there is a resurging interest in this technique due to the
      expanding scope of elderly patients being considered for the treatment of aortic
      stenosis. Herein, we describe our surgical technique and provide a systematic
      review of recent publications on AAC insertion, reporting that there is continued
      use and several modifications of this technique, such as performing it through a
      small thoracotomy without the use of the cardiopulmonary bypass. 

PMID- 23960620
TI  - Immediate- and medium-term effects of balloon pulmonary valvuloplasty in infants
      with critical pulmonary stenoses during the first year of life: A prospective
      single center study.
AB  - BACKGROUND: Balloon pulmonary valvuloplasty (BPV) represents the standard of
      management for all patients with severe pulmonary stenosis (PS) irrespective of
      their age. Nevertheless neonates and infants with critical PS represent a high
      risk group that needs to be studied. METHODS: The study population included 72
      infants with severe congenital valvular PS and four infants with imperforate
      pulmonary valve (PV) who were subjected to detailed history taking, full clinical
      examination, resting 12-lead ECG, Chest roentgenogram and transthoracic
      echocardiography. BPV was attempted in all infants with a peak-to-peak gradient
      across the PV of 50 mmHg or greater at catheterization-laboratory. Full
      echocardiographic evaluation was done 24 hours after the procedure as well as 3
      and 6 months later. RESULTS: Seventy-six infants with severe PS or imperforate PV
      with a mean age of 5.63 +/- 2.99 months were subjected to BPV with or without
      wire perforation. Immediately after the procedure patients had a significant
      reduction of the right ventricular systolic pressure (RVSP) (104.69 +/- 24.98 mm
      Hg Vs 43.6 +/- 13 mm Hg, p < 0.001) and RV-PA systolic pressure gradient (PG)
      (82.5 +/- 23.76 mm Hg Vs 17.35 +/- 8.96 mm Hg, p < 0.001). The immediate success
      rate defined as the drop in the RVSP to less than or equal to 50% of the baseline
      measurement was achieved in 85% of the cases. There was a progressive drop in the
      PG across the PV by Doppler echocardiogram throughout a follow-up period of six
      months from a mean of 93.3 +/- 28.2 mm Hg to a mean of 17.4 +/- 10.42 mm Hg (p <
      0.001). There was a significant increase of the mean PV annulus diameter after
      balloon dilatation (p < 0.001). There was also a highly significant inverse
      correlation between the growth of the pulmonary annulus and the annular size at
      the baseline before dilatation (r = -0.74, p value <0.001). The incidence of PR
      significantly increased immediately after BPV to 64% followed by a progressive
      decline over a 6 months period of follow-up to 20%. There was a significant
      decrease in the incidence of tricuspid regurgitation (TR) over the same period of
      follow-up (from 55.6% at baseline to less than 20% at follow-up). CONCLUSION: BPV
      is safe and effective to relieve critical PS in infants during the first year of
      life. The balloon promotes advantageous changes in both, pulmonary annulus and PG
      across the RVOT. In addition, the Doppler gradient observations during the follow
      up support the expectation that BPV is a "curative" therapy.

PMID- 23960621
TI  - Comparison of cardiac magnetic resonance with gated SPECT for evaluation of left
      ventricular function and volumes in patients with severe and multiple myocardial
      perfusion defects.
AB  - OBJECTIVES: Gated SPECT is an accurate technique for assessment of myocardial
      perfusion (MP), left ventricular ejection fraction (LVEF), end-diastolic volume
      (EDV) and end-systolic volume (ESV). However recent studies have concluded that
      there are large discrepancies in assessment of LVEF and volumes by gated SPECT in
      patients with multiple severe myocardial perfusion defects. We sought to
      investigate the correlation between LVEF and volumes calculated by gated SPECT
      and cardiac magnetic resonance (CMR) in patients with severe multiple perfusion
      defects who are referred for CMR. METHODS: Twenty-nine patients (20 male and 9
      female, mean age: 63 years +/- 11) with multiple severe fixed perfusion defects
      (mean 5 +/- 3 segments) were referred to undergo CMR. The average time between
      CMR and SPECT was 4 weeks. LVEF, EDV, and ESV were derived automatically from
      gated SPECT. In the CMR studies, the endocardial and epicardial borders were
      delineated manually in the short axis planes to calculate the LVEF and volumes.
      RESULTS: The different parameters were compared using linear regression, and
      correlation coefficients were calculated. Substantial correlation was found
      between CMR and gated SPECT for EDV: r = 0.7, p < 0.001. Moderate correlation
      between CMR and gated SPECT for LVEF: r = 0.5, p < 0.007 and ESV r =0 .53, p <
      0.003. CONCLUSION: Our data showed that the gated SPECT correlates substantially
      with MRI for measurement of EDV and moderately for ESV and LVEF in patients with
      multiple and severe perfusion defects. Thus, when accurate measurement is
      required, cardiac MRI is recommended.

PMID- 23960622
TI  - Safe and effective use of conscious sedation for defibrillation threshold testing
      during ICD implantation.
AB  - BACKGROUND: Over a period of years general anesthesia has been a standard
      anesthetic technique for defibrillation threshold (DFT) testing at the time of
      implant. DFT testing without general anesthesia cover has gained limited
      acceptance. Use of local anesthesia combined with deep sedation for DFT testing
      might facilitate and simplify these procedures by reducing the procedural time,
      staff time, avoiding inefficient service in organizing anesthetic cover; thereby
      improving patient compliance. OBJECTIVE: The objective of this study was to
      evaluate feasibility, safety and efficacy of conscious sedation for DFT testing
      during Implantable cardioverter defibrillators (ICD) implantation. METHOD: Data
      of 87 non-selected patients who achieved adequate sedation with titrated doses of
      midazolam and pethidine were analyzed retrospectively. These medications were
      administered by a circulating nurse under the supervision of the implanting
      physicians. All hemodynamic measures, treatment and complications were monitored
      and recorded throughout the procedure. RESULTS: A retrospective analysis of data
      from 87 patients who underwent ICD implantation and DFT testing under conscious
      sedation at our center was reported. The mean dose of midazolam and pethidine
      administered was 4.9 +/- 1.8 and 47.7 +/- 20 mg, respectively. During the period
      of conscious sedation, no patient depicted episode of sustained apnea. No major
      complication or mortality was reported. CONCLUSION: Use of conscious sedation as
      an alternative to the use of general anesthesia for DFT testing during ICD
      implantation is found to be feasible, safe and effective, with an added advantage
      of reduced procedural time and improved patient compliance.

PMID- 23960623
TI  - Percutaneous coronary intervention of a saphenous vein graft ostial stenosis in a
      patient with Bentall procedure.
AB  - Composite graft replacement of the aortic root and coronary reimplantation with
      or without coronary artery bypass surgery is the standard treatment for a variety
      of aortic root pathologies. Previously, percutaneous coronary intervention of
      either reimplanted coronary arteries or left/right coronary artery through cabrol
      graft has been described in post-Bentall patients. We describe percutaneous
      coronary intervention of a saphenous vein graft ostial stenosis in a patient with
      previous Bentall procedure and a vein graft to right coronary artery, which was
      complex and challenging. 

PMID- 23960624
TI  - Stress-induced cardiomyopathy (Tako-Tsubo) in a premenopausal woman: A case
      report from Saudi Arabia.
AB  - Tako-Tsubo cardiomyopathy (TTC) is a nonischemic cardiomyopathy characterized by
      reversible left ventricular dysfunction that is seen predominantly in
      postmenopausal women (>80%). The syndrome has symptoms that are similar to acute
      myocardial infarction, such as electrocardiogram changes (ST-segment elevation
      and subsequent giant T wave inversion) and abnormal cardiac enzymes. The clinical
      prognosis is usually benign. This article reports the first case of a TTC in a
      premenopausal Saudi woman. Early diagnosis of TTC excludes the use of stents,
      thrombolytics, and long-term coronary heart disease medications. 

PMID- 23960625
TI  - Ultrasound-guided insertion of pulmonary artery catheter: Case report.
AB  - This is a case report of a 17-year old girl, who presented with aortic valve
      regurgitation and patent ductus arteriosus, and she underwent aortic valve
      replacement (AVR) and (PDA) ligation. Because of the extensive thrill and
      pulsation in the neck due to carotid artery dilatation, pulmonary artery catheter
      (PAC) was inserted under ultrasound guidance. This case report is to encourage
      the use of ultrasound for the safe puncture of internal jugular vein for the
      insertion of central line and PAC, particularly in the case of aortic valve
      regurge patients where carotid artery dilatation expected. 

PMID- 23960627
TI  - Message from the president.

PMID- 23960626
TI  - Sixty seconds of asystole after exercise in a healthy person.

PMID- 23960629
TI  - Down's syndrome and myocardial reperfusion injury.
AB  - Down syndrome is known to be an independent risk factor for mortality after
      surgical repair of congenital heart anomalies. It is also associated with
      neurodegenerative disease and accelerated aging. The mechanism of the latter
      features has been attributed to abnormal handling of oxygen-free radicals as well
      as mitochondrial dysfunction. These properties also place the child with Down
      syndrome at a risk of an exaggerated myocardial ischemia/reperfusion injury. A 6
      month old child with Down syndrome is reported who suffered from obvious clinical
      ischemia/reperfusion injury following an uncomplicated repair of complete AV
      canal. Both intraoperative as well as postoperative echocardiography documented a
      satisfactory technical repair. After resting the heart on ECMO the child's
      myocardial function returned to normal. The mechanisms by which patients with
      Down syndrome are at risk of ischemia/reperfusion injury are reviewed. Future
      studies should focus on specific approaches for myocardial protection in the
      child with Down syndrome undergoing cardiac surgery. 

PMID- 23960628
TI  - The clinical significance of cardiac troponins in medical practice.
AB  - Troponins are regulatory proteins that form the cornerstone of muscle
      contraction. The amino acid sequences of cardiac troponins differentiate them
      from that of skeletal muscles, allowing for the development of monoclonal
      antibody-based assay of troponin I (TnI) and troponin T (TnT). Along with the
      patient history, physical examination and electrocardiography, the measurement of
      highly sensitive and specific cardiac troponin has supplanted the former gold
      standard biomarker (creatine kinase-MB) to detect myocardial damage and estimate
      the prognosis of patients with ischemic heart disease. The current guidelines for
      the diagnosis of non-ST segment elevation myocardial infarction are largely based
      on an elevated troponin level. The implementation of these new guidelines in
      clinical practice has led to a substantial increase in the frequency of
      myocardial infarction diagnosis. Automated assays using cardiac-specific
      monoclonal antibodies to cardiac TnI and TnT are commercially available. They
      play a major role in the evaluation of myocardial injury and prediction of
      cardiovascular outcome in cardiac and non-cardiac causes. In this review we
      discuss the clinical applications of cardiac troponins and the interpretation of
      elevated levels in the context of various clinical settings. 

PMID- 23960630
TI  - Gender-related differences in the presentation, management, and outcomes among
      patients with acute coronary syndrome from Oman.
AB  - OBJECTIVE: To assess gender-related differences in the presentation, management,
      and in-hospital outcomes among acute coronary syndrome (ACS) patients from Oman.
      METHODS: Data were analyzed from 1579 consecutive ACS patients from Oman during
      May 8, 2006 to June 6, 2006 and January 29, 2007 to June 29, 2007, as part of
      Gulf RACE (Registry of Acute Coronary Events). Analyses were conducted using
      univariate and multivariate statistical techniques. RESULTS: In this study, 608
      (39%) patients were women with mean age 62 +/- 12 vs. 57 +/- 13 years (p <
      0.001). More women were seen in the older age groups (age <55 years: 25% vs. 43%,
      55-74 years: 60% vs. 49% and >75 years: 15% vs. 8%; p < 0.001). Women had higher
      frequencies of diabetes, hypertension, hyperlipidemia, obesity, angina, and
      aspirin use, but less history of smoking. Women were significantly less likely to
      have ischemic chest pain, ST-elevation myocardial infarction (STEMI), non-STEMI
      and were more likely to have dyspnea, unstable angina, ST depression and left
      bundle branch block. Both groups received ACS medications and cardiac
      catheterization equally; however, women received anticoagulants (88% vs. 79%; p <
      0.001), angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II
      receptor blockers (ARBs) (70% vs. 65%; p = 0.050) more and clopidogrel less (20%
      vs. 29%; p < 0.001). Women experienced more recurrent ischemia and heart failure
      but with similar in-hospital mortality (4.6% vs. 4.3%) even after adjusting for
      age (p = 0.500). CONCLUSIONS: Women admitted with ACS were older than men, had
      more risk factors, presented differently with no difference in hospital
      mortality. This is similar to Gulf RACE study except for mortality. Women
      received anticoagulants/ACEIs /ARBs more but were under-treated with clopidogrel.

PMID- 23960631
TI  - Can lung volumes and capacities be used as an outcome measure for phrenic nerve
      recovery after cardiac surgeries?
AB  - Phrenic nerve is the main nerve drive to the diaphragm and its injury is a well
      known complication following cardiac surgeries. It results in diaphragmatic
      dysfunction with reduction in lung volumes and capacities. This study aimed to
      evaluate the objectivity of lung volumes and capacities as an outcome measure for
      the prognosis of phrenic nerve recovery after cardiac surgeries. In this
      prospective experimental study, patients were recruited from Cardio-Thoracic
      Surgery Department, Educational-Hospital of College of Medicine, Cairo
      University. They were 11 patients with right phrenic nerve injury and 14 patients
      with left injury. On the basis of receiving low-level laser irradiation, they
      were divided into irradiated group and non-irradiated group. Measures of phrenic
      nerve latency, lung volumes and capacities were taken pre and post-operative and
      at 3-months follow up. After 3 months of low-level laser therapy, the irradiated
      group showed marked improvement in the phrenic nerve recovery. On the other hand,
      vital capacity and forced expiratory volume in the first second were the only
      lung capacity and volume that showed improvement consequent with the recovery of
      right phrenic nerve (P value <0.001 for both). Furthermore, forced vital capacity
      was the single lung capacity that showed significant statistical improvement in
      patients with recovered left phrenic nerve injury (P value <0.001). Study
      concluded that lung volumes and capacities cannot be used as an objective outcome
      measure for recovery of phrenic nerve injury after cardiac surgeries. 

PMID- 23960632
TI  - Do pre-adenotonsillectomy echocardiographic findings change postoperatively in
      children with severe adenotonsillar hypertrophy.
AB  - PURPOSE: Hypertrophy of adenotonsillar tissue is one of the most common problems
      in childhood age and causes upper airway obstruction and even obstructive sleep
      apnea symptoms in severe forms. The aim of this study is to evaluate the changes
      of pre-adentonsillectomy echocardiographic findings after operation. MATERIAL AND
      METHODS: From August 2007 to November 2008, 55 children with adenotonsillar
      hypertrophy and obstructive-sleep symptoms (aged 3-11 years old of which 35 were
      males and 20 females) were randomly selected. Preoperatively echocardiography was
      performed for all patients by the pediatric cardiologist. In control group 55
      children who referred to otolaryngology clinic because of non adenotonsillar
      related disease evaluated. One month and six months after operation, patients
      with positive findings were followed up and again echocardiography was performed
      separately. RESULTS: No complaints of apnea were reported. Tonsillar grades of
      all cases were type III or IV. The preoperative mean pulmonary arterial pressure
      levels of the 4 (7.3%) children were higher than normal range (25 mm Hg) and it
      decreased significantly after operation (P < 0.000) (Preoperative MPAP = 32 +/- 3
      mm Hg, and six months postoperative follow up, MPAP = 11 +/- 5 mm Hg). All the
      patients' parents complained about severe open mouth snoring, agitated sleep and
      hyperpnoea of their children. The preoperative tricuspid regurgitation pressure
      level of 7 children was higher than normal range and it decreased significantly
      after operation (P < 0.000 preoperative TR = 34 +/- 8 mm Hg postoperative TR = 19
      +/- 6 mm Hg). AC/ET in these seven patients were lower than 0.4. In control group
      echocardiography findings are normal. CONCLUSION: Severe chronic hypertrophic
      adenotonsillar tissue caused higher tricuspid regurgitation pressure and mean
      pulmonary arterial pressure.

PMID- 23960633
TI  - Coronary artery anomalies: A diagnostic challenge.
AB  - Coronary artery anomalies (CAAs) are found in approximately 1% of all patients
      undergoing coronary angiography and in 0.3% of patients undergoing autopsy
      (Roberts, 1986). CAAs may be classified into those of origin and course,
      intrinsic coronary arterial anatomy, and coronary termination (Angelini et al.
      2002). The most common malformation is abnormal origin and course, origin of a
      coronary artery from a wrong aortic sinus of Valsalva; either the right from the
      left coronary sinus or the left from the right coronary sinus; these anomalies
      must be excluded in young adults with typically ischemic- sounding chest pain or
      syncope. Anomalies coronary artery termination typically presented as coronary
      artery fistula, commonly the right coronary artery is affected, although, left
      sided coronary artery fistulae are well documented (Gandy et al. 2004). The
      anomalies of intrinsic coronary arterial anatomy, such as ostial stenosis,
      Artesia, and single, absent, or hypoplastic coronary arteries are rare but may
      have clinical importance. 

PMID- 23960634
TI  - Coronary sinus diverticulum as a cause of resistant posteroseptal pathway
      ablation.
AB  - Coronary sinus (CS) anomalies such as diverticulum, persistent left superior vena
      cava or CS ostium dilatation are predominantly found in patients with accessory
      pathway-related tachycardias. Diverticulum of the proximal CS found in 7-11% of
      patients with postero-septal or left posterior manifests accessory pathways. We
      reported a 28 year old gentleman with manifested postero-septal accessory
      pathway, who underwent repeat electrophysiological study (EPS) and radiofrequency
      ablation for previously failed ablation. Huge CS diverticulum was identified by
      angiography as a reason for resistant accessory pathway. Successful RF ablation
      was achieved at the neck of the diverticulum without complications. Other
      associated anomalies were ruled out by cardiac computerized tomography (CT) and
      trans-esophageal echocardiography. 

PMID- 23960635
TI  - Unusual cause of neonatal cyanosis.
AB  - We present a case of a full-term female neonate who presented at 6 h of age with
      severe cyanosis and was partially responsive to oxygen supplementation. An
      echocardiogram showed an isolated congenital severe tricuspid valve insufficiency
      due to rupture of the papillary muscle of the anterior tricuspid valve leaflet.
      Magnesium sulfate was infused to lower the pulmonary resistance and thus
      enhancing the antegrade pulmonary blood flow. Ductal patency was secured by
      prostaglandin infusion thus providing an additional pulmonary blood flow through
      the ductus arteriosus. The above measures were adequate to stabilize the patient
      with no further deterioration or the need for other supportive measures such as
      Nitric Oxide therapy or extracorporeal membrane oxygenation (ECMO). Therefore,
      early diagnosis and adequate measures to improve the pulmonary blood flow are
      mandatory, important pre-operative measures in the management of these patients. 

PMID- 23960636
TI  - Acute intra-coronary thrombus on cardiac CT imaging.

PMID- 23960638
TI  - Message from the president of saudi heart association.

PMID- 23960637
TI  - Echocardiography in mitral stenosis.
AB  - Echocardiography plays a major role in diagnosis, etiology and severity of Mitral
      Stenosis (MS), analysis of valve anatomy and decision-making for intervention.
      This technique has also a crucial role to assess consequences of MS and follow up
      of patients after medical or surgical intervention. In this article we review the
      role of conventional echocardiography in assessment of mitral stenosis and future
      direction of this modality using 3D echocardiography. 

PMID- 23960639
TI  - Diagnosis and management of common fetal arrhythmias.
AB  - Fetal arrhythmias are detected in at least 2% of unselected pregnancies during
      routine obstetrical scans. Most common are transient, brief episodes of a slow or
      fast heart rate or of an irregular heart rhythm. Less common are prolonged or
      persistent abnormalities such as supraventricular tachycardia and complete heart
      block which may lead to low cardiac output, fetal hydrops and demise. The
      objectives of this review are to update the reader on the diagnosis and
      management of the more common arrhythmias. 

PMID- 23960641
TI  - Nucleoside transport inhibitor, dipyridamole, induced myocardial protection
      following hemorrhagic shock in ex vivo perfused rat hearts.
AB  - INTRODUCTION: Successful protection against post-resuscitation myocardial injury
      is not available for trauma patients. Whereas intensive improvement in
      resuscitation strategies reduce myocardial injury, death among trauma patients
      are among the highest in the world due to myocardial dysfunction and multiple
      organ failure. Dipyridamole is a nucleoside transport inhibitor. Recent studies
      have shown that elevation of serum adenosine caused by dipyridamole improve
      cardiac function. The purpose of the present study was to examine the myocardial
      protective effects of dipyridamole therapy following 1 h of hemorrhagic shock.
      METHODS: Sprague-Dawley rats were used. The study consisted of three phases:
      Phase I to examine the direct effects of dipyridamole on myocardial function by
      perfusion of the isolated hearts with Krebs Henseleit buffer (KHB) + dipyridamole
      on the Langendorff apparatus. Phase II examined the protective effects of
      dipyridamole following 60 min of hemorrhagic shock (HS) by ex vivo treatment with
      dipyridimole 20 MUg/L for 5 min followed by resuscitation with KHB for 55 min.
      Phase III: 60 min HS followed by in vivo treatment by injecting 1 ml of (20
      MUg/L) dipyridamole intra-arterially, and resuscitation for 30 min. Myocardial
      protection was assessed by measuring left ventricular generated pressure (LVGP)
      and end diastolic pressures (LVEDP). RESULTS: During ex vivo resuscitation,
      hearts from dipyridamole treated animals had significantly higher LVGP, and
      significantly lower LVEDP versus controls. CONCLUSION: Dipyridamole therapy
      produces protection against post-resuscitation myocardial injury in rats.

PMID- 23960640
TI  - Evaluation of aggressive heart rate reduction in patients with stable angina.
AB  - BACKGROUND: There is a strong correlation between heart rate and myocardial
      ischemia, cardiovascular diseases, and life expectancy in general; however, heart
      rate has been neglected as an important risk factor as well as a therapeutic
      opportunity. PURPOSE: To investigate the effect of aggressive heart rate
      reduction (50 ? HR ? 60 bpm) on anti-ischemic and anti-anginal efficacy, left
      ventricular function, exercise tolerance and quality of life in patients with
      stable coronary artery disease with or without left ventricular dysfunction
      during 4 months. METHODS: A total of 159 patients presented with stable CAD
      without clinical heart failure symptoms were included in a open-label, non
      comparative, prospective clinical study between June 2009 to February 2010 in
      King Abdul Aziz Specialist Hospital, Taif, KSA, Al Hayah National Hospital,
      Khamis Mushyt, KSA and Critical care department, Cairo University, Egypt. All
      included patients were, in addition to the ant ischemic treatment, subjected to
      aggressive heart rate control starting by beta blocker titrated to the maximum
      dose as tolerated, then Ivabradine added if the target heart rate is not achieved
      or rate control started by Ivabradine if beta blockers are contraindicated.
      Exercise treadmill test (ETT) to assess exercise capacity using time to 1 mm ST
      segment depression in milliseconds, ejection fraction (EF) assessed by
      transthoracic echocardiography and frequency of angina attacks and the use of
      sublingual nitroglycerin per week during the last week were evaluated during a
      follow-up for 4 months. The patients were divided into two groups, group-I
      (patients achieved a resting heart rate between 50 and 60 bpm with heart rate
      reduction treatment) and group-II (patients with resting HR >60 bpm in spite of
      maximum treatment for heart rate reduction). RESULTS: The resting heart rate was
      significantly reduced from 77.98 +/- 8.7 at baseline to 60.68 +/- 4.34 bpm after
      4 months of treatment, P < 0.001. The frequency of angina pectoris attacks had
      been significantly reduced from 2.14 +/- 1.27 to 0.48 +/- 0.58 attacks per week,
      P < 0.001 and the highest significant reduction was observed with group-I. Also,
      the frequency of use sublingual nitrate therapy was significantly reduced from
      1.38 +/- 1.1 tablet per week at the last week before the study to 0.12 +/- 0.33
      tablet per week during the last week after 4 months of treatment, P < 0.001 and
      the reduction was more significantly with group-I. Exercise treadmill test
      demonstrated statistically significant increase in the time to 1 mm ST-segment
      depression from 357.36 +/- 66.73 at baseline to 387.96 +/- 65.19 ms. after 4
      months with P < 0.001. The degree of improvement was significantly higher for
      group-I (from 358.06 +/- 68.81 at baseline to 391.71 +/- 69.01 after 4 months
      with P < 0.001) than that of group-II (from 356.11 +/- 64.8 at baseline to 381.27
      +/- 59.08 after 4 months with P < 0.001). Ejection fraction showed a
      statistically significant increase from 59.76 +/- 6.86 at baseline to 61.04 +/-
      5.35 after 4 months with P < 0.001. CONCLUSION: This study indicates that heart
      rate reduction has been associated with an improvement in quality of life in
      patients with stable coronary artery disease, presenting new opportunities for
      treatment.

PMID- 23960642
TI  - Assessment of pulmonary function tests in cardiac patients.
AB  - This study was aimed to assess the pulmonary function tests (PFTs) in cardiac
      patients; with ischemic or rheumatic heart diseases as well as in patients who
      underwent coronary artery bypass graft (CABG) or valvular procedures. For the
      forty eligible participants, the pulmonary function was measured using the
      spirometry test before and after the cardiac surgery. Data collection sheet was
      used for the patient's demographic and intra-operative information. Cardiac
      diseases and surgeries had restrictive negative impact on PFTs. Before surgery,
      vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in the
      first second (FEV1), ratio between FEV1 and FVC, and maximum voluntary
      ventilation (MVV) recorded lower values for rheumatic patients than ischemic
      patients (P values were 0.01, 0.005, 0.0001, 0.031, and 0.035, respectively).
      Moreover, patients who underwent valvular surgery had lower PFTs than patients
      who underwent CABG with significant differences for VC, FVC, FEV1, and MVV tests
      (P values were 0.043, 0.011, 0.040, and 0.020, respectively). No definite
      causative factor appeared to be responsible for those results although mechanical
      deficiency and incisional chest pain caused by cardiac surgery are doubtful. More
      comprehensive investigation is required to resolve the case. 

PMID- 23960644
TI  - Tenecteplase in prosthetic mitral valve thrombosis.
AB  - In the few reported cases of prosthetic mitral valve thrombosis, where surgical
      intervention was considered as high risk, fibrinolytic therapy had proved life
      saving. The authors present clinical, laboratory, and imaging data from such a
      patient, with prosthetic mitral valve thrombosis and its successful management
      with tenecteplase. The use of tenecteplase as a viable fibrinolytic agent for the
      first time was justified, due to the lack of immunogenicity concerns compared to
      streptokinase. 

PMID- 23960643
TI  - A dramatic decline in university hospital admissions of acute rheumatic fever in
      the eastern region of Saudi Arabia.
AB  - BACKGROUNDS: Acute rheumatic fever (ARF) and its sequel, chronic valvular heart
      disease are the most important causes for cardiovascular morbidity and mortality
      worldwide and mainly in developing countries. However, the incidence of ARF has
      declined in developed countries during the second half of 20th century. MATERIAL
      AND METHODS: The case files of all patients admitted as new cases of ARF over ~11
      years and 8 months, both in pediatric and medical departments of a university
      hospital located in the eastern region of Saudi Arabia were reviewed. The
      demographic and clinical data and the frequency of the new cases were compared
      with the data that have been published by us 10 years ago from the same hospital
      during a similar period of time (11 years and 8 months). RESULTS: In the current
      study there was a significant decline in the frequency of admission of cases of
      ARF as compared to our previous study during a similar period of time, with a
      frequency rate of 12 cases per 100.000 hospitalizations versus 45 cases per
      100.000 hospitalizations, respectively, P < 0.001. Dyspnea and chest pain as
      clinical features of acute rheumatic carditis (ARC) were less frequent in the
      current study as compared to the previous study (35% versus 44%, P = 0.02 and 10%
      versus 28.6%, P = 0.031). The subgroup analysis revealed also a decreased
      frequency of the clinical features of ARC in pediatric age group in the current
      study as compared to our previous study. CONCLUSION: There is a significant
      decline in the frequency of new hospital admissions due to ARF. This decline was
      associated with similar decline in the frequency of the manifestations of ARC
      especially in pediatric age group (1-12 years).

PMID- 23960645
TI  - Allergic reaction to abciximab with atypical manifestations.
AB  - Abciximab (ReoPro, Eli Lilly and Company, Indianapolis, Indiana) is an
      intravenous agent that had been approved for treatment of acute coronary syndrome
      undergoing coronary interventions. It is a chimeric monoclonal antibody fragment
      that binds to the glycoprotein IIb/IIIa receptor with a potential for the
      development of an immune response to variable portions within the antigen binding
      site following its administration. We describe a 58-year-old man who developed
      sudden headache, short of breath, choking and restlessness after receiving
      Abciximab for coronary intervention. Discontinuation of abciximab and
      administration of intravenous fluids, steroid and antihistamines led to
      improvement of his symptoms gradually. 

PMID- 23960646
TI  - Drug-eluted stent fracture occurred within 3 years lead to chronic total
      occlusion and aneurysm.

PMID- 23960647
TI  - Atrial septal aneurysm and cryptogenic stroke.

PMID- 23960648
TI  - Myocardial perfusion single photon computed tomography: An Atlas.
AB  - The purpose of this Teaching Atlas is to provide the reader with both image
      recognition and an understanding of the basis for myocardial perfusion single
      photon computed tomography (SPECT) images interpretation. The objective is to
      present a wide variety of myocardial perfusion cases, both relevant and to some
      extent in-depth, to be used by nuclear cardiologist/nuclear medicine physicians
      as well as trainees in cardiology, radiology and nuclear medicine. In recent
      years, the field of nuclear cardiology has made major advances in both
      radiopharmaceuticals and instrumentation. Attenuation correction techniques have
      and will continue to improve the diagnostic accuracy of myocardial perfusion
      SPECT. Several attenuation correction aspects are included in this Atlas. 

PMID- 23960649
TI  - Message from the Editor-in-Chief.

PMID- 23960650
TI  - Clinical and microbiological profiles of infective endocarditis in a tertiary
      hospital in Aseer region, Saudi Arabia.
AB  - OBJECTIVES: We aimed to evaluate demographic data, underlying cardiac
      abnormalities, clinical profile, microbiological features, treatments and
      complications of infective endocarditis (IE) in a tertiary hospital in Aseer
      region, Saudi Arabia. METHODS: A retrospective study of all cases with the
      diagnosis of definite endocarditis according to modified Duke Criteria admitted
      to ACH between May 2002 and April 2007. Data were reviewed on demographic and
      clinical data, underlying cardiac disease, microbiological findings, treatments
      and complications of IE. RESULTS: The study included 44 patients (28 males and 16
      females; mean age 31.1 +/- 16 years; range 13-65 years). Infective endocarditis
      developed on a native valve in 31 (70.5%), a mechanical prosthetic valve in 10
      (22.7%), mitral valve prolapse in 2 (4.5%) and ventricular septal defect in 1
      (2.3%). Rheumatic heart disease in 31 cases (70.5%) was the most common
      preexisting valvular abnormality in native valve endocarditis. The mitral valve
      was the most commonly affected valve 28 (63.6%). Fever occurred in 40 (90.9%) of
      the cases. Electrocardiography was abnormal in 34 cases (77.3%). Trans-thoracic
      and/or trans-esophageal echocardiography showed a vegetation in 22 (50%).
      Staphylococci in 10 cases (22.7%) and Streptococci in 8 cases (18%) were the most
      common causative agents and cultures were negative in 20 cases (45.5%). Twenty
      two patients (50%) underwent surgical treatment. Congestive heart failure
      occurred in 16 (36.4%) cases, atrial fibrillation in 6 (13.6%) cases, and
      cerebrovascular accidents in 4 (9%) cases. CONCLUSION: Our data reflects the
      clinical and microbiological profiles of IE in a tertiary hospital in Aseer
      region, Saudi Arabia.

PMID- 23960651
TI  - Evaluation of femoral approach to coronary sinus catheterisation in
      electrophysiological and ablation procedures: Single centre experience.
AB  - BACKGROUND: It has been reported that the cannulation of coronary sinus (CS) from
      the femoral approach is safer than the traditional subclavian approach but is
      associated with a lower rate of success. We aimed to test the validity of this
      claim. METHOD: We evaluated retrospectively 1320 consecutive patients who
      underwent electrophysiological study (EPS) or ablation over a period of three
      years using a prospectively collected data. In cases requiring CS cannulation, it
      was attempted first from the femoral approach, switching if necessary to a
      subclavian approach when the femoral route failed. RESULTS: Out of 1320 patients,
      1165 (88.3%) required CS cannulation. The CS was successfully cannulated from the
      femoral approach in 99.3% of the cases in which it was attempted. One patient
      (0.09%) developed transient first degree atrioventricular block during an
      ablation procedure for AV nodal re-entrant tachycardia during cannulation of the
      CS that resolved within 3 min. Femoral access failed in 8 patients. In 4 of these
      cases, the procedure was concluded using CS cannulation via subclavian or jugular
      venous access. In the other 4 cases, the procedure was concluded successfully
      without CS cannulation, including an AF ablation in which CS cannulation proved
      impossible by either subclavian or femoral approach. CONCLUSION: Femoral access
      can be used for CS cannulation with a high rate of procedural success in the vast
      majority of patients undergoing EPS and ablation. This approach is safe, and
      associated with a high rate of procedural success.

PMID- 23960652
TI  - Assessment of cardiac involvement of hepatitis C virus; tissue Doppler imaging
      and NTproBNP study.
AB  - INTRODUCTION: Hepatitis C disease burden is substantially increasing in Egyptian
      community, it is estimated that prevalence of Hepatitis C virus (HCV) in Egyptian
      community reach 22% of total population. Recently there is a global alert of HCV
      cardiovascular complications. OBJECTIVE: To evaluate LV diastolic functions of
      HCV patients using tissue Doppler Imaging and NTPBNP. METHODS: 30 HCV patients of
      30 years, sex & BMI matched controls were evaluated by PCR, ECG, Echocardiography
      "conventional Doppler, pulsed wave tissue Doppler (PW-TD), strain rate imaging" &
      NTPBNP to assess LV diastolic functions. Mean age was 32.8 years +/- 5.1 in HCV
      group, 29.8 years +/- 6.6 in control group. Cardiovascular anomalies and
      predisposing factors were excluded. RESULTS: HCV group has shown significant
      increase in QTc interval, significant statistical increase in A wave,
      deceleration time; (p < 0.05), highly significant decrease in tissue Doppler E a
      (p < 0.001), highly significant decrease in A a (p < 0.001), highly significant
      increased E/E a ratio (p value < 0.001), significant decrease in E a/A a ratio
      and significant increase in SRa (p < 0.05). NTPBNP levels showed highly
      significant increase with mean value 222 pg/ml +/- 283 in HCV group and 32.7
      pg/ml +/- 21.2 in control group (p value < 0.001). The best cut-off value of
      NTPBNP to detect diastolic dysfunction in HCV group was 213 pg/ml. No statistical
      differences in SRe/SRa and E/SRe ratios were observed, however they had
      significant correlation with NTPBNP level and tissue Doppler parameters. The best
      cut-off value of E/SRe ratio to detect diastolic dysfunction in HCV group was
      0.91, with 75% sensitivity and 100% specificity. CONCLUSION AND RECOMMENDATION:
      This data show the first direct evidence that HCV infection causes diastolic
      dysfunction without any other predisposing factors, probably due to chronic
      inflammatory reaction with mild fibrosis in the heart. Previous studies did not
      follow strict inclusion and exclusion criteria that confirm the independent role
      of HCV to cause diastolic dysfunction. Tissue Doppler was more sensitive to
      diagnose diastolic dysfunction than conventional Doppler.

PMID- 23960653
TI  - Resting heart rate in patients with ischemic heart disease in Saudi Arabia and
      Egypt.
AB  - AIM: To assess the level of resting heart rate (RHR) in an outpatient population
      presenting with stable coronary artery disease (CAD) as well as to measure its
      association with current therapeutic management strategies for cardiovascular
      events. MATERIALS AND METHODS: A multi-center cross-sectional survey was carried
      out in Saudi Arabia and Egypt over a three month period (between January 2007 and
      April 2007). 2049 patients with CAD without clinical heart failure (HF) were
      included in this study through "cluster sampling". RHR was measured by manual
      palpitation. RESULTS: Mean age of CAD patients was 56.7 +/- 10.4 and the mean RHR
      was 78.9 +/- 13.9 b/m. 1686 patients (83.1%) were on beta-blockers for whom the
      RHR was 78.5 +/- 14.0 b/m (95.5% had RHR ? 60 b/m, which is higher than
      recommended by the guidelines). 1094 (73.5%) of patients on beta-blockers were on
      a lower dose, probably to avoid the complications associated with such a class.
      Among those not on beta-blockers (16.9%), RHR was 80.9 +/- 13.0 b/m. Moreover, 98
      patients (4.8%) were on calcium channel blocker (diltiazem or verapamil) but not
      on beta-blockers, for whom the RHR was 80.9 +/- 12.0 b/m. Finally, 163 patients
      (8.0%) were on both beta-blockers and the calcium channel blocker, and their RHR
      was 79.0 +/- 14.4 b/m. CONCLUSION: Optimal target RHR has not been achieved in a
      significant number of screened patients. Achievements of such targets are known
      to decrease mortality and to improve survival.

PMID- 23960656
TI  - Coronary computed tomography angiography in a patient with atrial fibrillation,
      case report.
AB  - Atrial fibrillation (AF) is the most common persistent arrhythmia. It is
      associated with wide range of cardiac clinical conditions. Because of variable
      duration of cardiac cycle resulting in reduced image quality, AF has been
      considered relative contraindication for performing coronary computed tomography
      angiography (CCTA). However, recent reports have suggested that newer dual source
      scanner with higher temporal resolution can be used in patients with AF (Oncel et
      al., 2007; Wolak et al., 2008; Rist et al., 2009). Image quality can be
      maintained if heart rate is lowered to less than 70 beats per minute. However,
      high heart rate can still be challenging. Mapping systolic phase with the use of
      absolute delay reconstruction algorithm has been shown to provide better image
      quality. In this article, we present a case of patient with chronic AF and in
      whom coronary examination was required before going to repair of aortic root
      dissection. CCTA, with the use of absolute delay reconstruction algorithm,
      provided diagnostic image quality of the coronary arteries. 

PMID- 23960655
TI  - The importance of utilizing 24-h Holter monitoring as a non-invasive method of
      predicting the mechanism of supraventricular tachycardia.
AB  - Despite the emergence of advanced invasive technology in identifying the various
      types of arrhythmia mechanisms, 24-h ambulatory electrocardiogram monitoring as a
      non-invasive method remains an invaluable informative tool in delineating such
      mechanisms. Furthermore, one observational study has supported the utilization of
      24-h Holter monitoring in exploring AV Node (AVN) characteristics sufficiently in
      correlation with invasive studies when limited to patients without Wolf Parkinson
      White syndrome showing a positive predictive value of 98% in their
      supraventricular tachycardia (SVT) assessment (Fukuda et al., 2005). We describe
      in this report suspected tachycardia initiation mechanism in three SVT cases
      based on 24-h Holter recordings. Premature atrial contraction with subsequent AVN
      fast pathway conduction block initiated the common type AVN re-entrant
      tachycardia (AVNRT). Dual AVN physiology was documented during the
      electrophysiological studies in all three cases and a definitive therapy was
      achieved by the AVN slow pathway modification. 

PMID- 23960654
TI  - Baseline characteristics, management practices, and in-hospital outcomes of
      patients with acute coronary syndromes: Results of the Saudi project for
      assessment of coronary events (SPACE) registry.
AB  - OBJECTIVES: The Saudi Project for Assessment of Coronary Events (SPACE) registry
      is the first in Saudi Arabia to study the clinical features, management, and in
      hospital outcomes of acute coronary syndrome (ACS) patients. METHODS: We
      conducted a prospective registry study in 17 hospitals in Saudi Arabia between
      December 2005 and December 2007. ACS patients included those with ST-elevation
      myocardial infarction (STEMI), non-ST elevation myocardial infarction and
      unstable angina; both were reported collectively as NSTEACS (non-ST elevation
      acute coronary syndrome). RESULTS: 5055 patients were enrolled with mean age +/-
      SD of 58 +/- 12.9 years; 77.4% men, 82.4% Saudi nationals; 41.5% had STEMI, and
      5.1% arrived at the hospital by ambulance. History of diabetes mellitus was
      present in 58.1%, hypertension in 55.3%, hyperlipidemia in 41.1%, and 32.8% were
      current smokers; all these were more common in NSTEACS patients, except for
      smoking (all P < 0.0001). In-hospital medications were: aspirin (97.7%),
      clopidogrel (83.7%), beta-blockers (81.6%), angiotensin converting enzyme
      inhibitors/angiotensin receptor blockers (75.1%), and statins (93.3%). Median
      time from symptom onset to hospital arrival for STEMI patients was 150 min (IQR:
      223), 17.5% had primary percutaneous coronary intervention (PCI), 69.1% had
      thrombolytic therapy, and 14.8% received it at less than 30 min of hospital
      arrival. In-hospital outcomes included recurrent myocardial infarction (1.5%),
      recurrent ischemia (12.6%), cardiogenic shock (4.3%), stroke (0.9%), major
      bleeding (1.3%). In-hospital mortality was 3.0%. CONCLUSION: ACS patients in
      Saudi Arabia present at a younger age, have much higher prevalence of diabetes
      mellitus, less access to ambulance use, delayed treatment by thrombolytic
      therapy, and less primary PCI compared with patients in the developed countries.
      This is the first national ACS registry in our country and it demonstrated
      knowledge-care gaps that require further improvements.

PMID- 23960657
TI  - Very delayed coronary stent fracture: A case report.
AB  - A stent fracture is an emerging complication of the coronary stents. There are
      numerous risk factors for stent fractures; which include forceful exaggerated
      motion in the atrioventricular groove seen in right coronary artery, long stent,
      an ostial lesion at the point of maximum curvature in a tortuous vessel, stent
      over-expansion, stent overlapping with different size stents, complex lesion
      after stenting of a totally occluded vessel, Cypher stent and a highly mobile
      segment causing high mechanical stress. Furthermore, chronic stretch at specific
      vessel sites as bends may lead to late occurrence of fracture. Here we report a
      case of 40-year-old male who had two overlapping Cypher stents (3.0 * 13 mm and
      2.75 * 18 mm) deployed at mid left anterior descending artery 2 years earlier
      presented with progressive chest pain. 

PMID- 23960658
TI  - Type B aortic injury by volume rendered CT aortogram.

PMID- 23960659
TI  - Cardiac magnetic resonance imaging: A teaching atlas with emphasizing current
      clinical indications.
AB  - Cardiovascular magnetic resonance (CMR) is an amazing technology that continues
      to provide new innovative approaches for evaluating the heart and blood vessels.
      It can assess cardiac morphology, function, perfusion, viability, coronary and
      peripheral arteries, and metabolism and tissue characterization. The basic pulse
      sequences of CMR include; Spin Echo, Gradient echo, and Steady stet free
      precision. Current clinical indications of CMR are multiple and continuously
      evolving. CMR often works in complementary fashions to other cardiac imaging
      techniques or to resolve residual diagnostic dilemma. The purpose of this
      illustrative review is to review current clinical applications of CMR and to
      provide physicians and technologists with simple, and regular CMR cases form
      daily practice. Each case discusses briefly the related clinical history,
      followed by CMR imaging findings, and simple discussion to highlight the role of
      CMR in a particular cardiovascular disorder. 

PMID- 23960660
TI  - Message from the Editor-in-Chief.

PMID- 23960661
TI  - Efficacy of a single dose intravenous heparin in reducing sheath-thrombus
      formation during diagnostic angiography: A randomized controlled trial.
AB  - BACKGROUND: Femoral arterial sheath thrombosis and distal embolization are well
      recognized complications of cardiac catheterization but the occlusion is
      extremely rare. Heparinized saline flushes are used during diagnostic coronary
      angiography to prevent thrombus formation within the sheath lumen. However, the
      use of prophylactic intravenous heparin following the femoral arterial sheath
      insertion is controversial. The aim of this study is to evaluate the
      effectiveness of 2000 units of intravenous heparin bolus in comparison to a
      saline placebo on the thrombus formation within the arterial sheath during the
      diagnostic coronary angiography. METHODS: Eligible patients were randomized to
      receive either a study drug or placebo at the time of femoral sheath insertion.
      The sheath was aspirated and flushed for any presence of thrombus after each
      catheter exchange and at the end of the procedure. Five milliliters of blood were
      extracted and visualized on clean gauze followed by a saline flush. The primary
      end-point was the effectiveness of the study drug on reducing the incidence of
      sheath-thrombus formation. RESULTS: Three hundred and twenty patients were
      randomized into two arms. Three hundred and four patients were analyzed: 147
      patients in heparin arm and 157 patients in placebo arm after exclusion of 13
      patients in heparin arm and three in placebo arm because of incomplete reports.
      The baseline characteristics were similar and sheath-thrombi formation was
      observed in 20% of the total cohort. Of the heparin arm, 12% (19 patients)
      developed sheath-thrombus formation, whereas 26% (42 patients) in the placebo
      arm, p-value = 0.002. An adjusted logistic regression model showed that the only
      predictor for the sheath-thrombus formation was the study drug (i.e. heparin).
      The odds ratio of developing a thrombus in the control arm was 2.5 (95% CI: 1.4
      4.5, p = 0.003). There were no bleeding events observed. CONCLUSION: The risk of
      thrombus formation is significant and intravenous heparin significantly reduced
      thrombus formation during diagnostic coronary angiography, with no excess
      bleeding events.

PMID- 23960662
TI  - Age and its relationship to acute coronary syndromes in the Saudi Project for
      Assessment of Coronary Events (SPACE) registry: The SPACE age study.
AB  - OBJECTIVE: To characterize risk profile of acute coronary syndrome (ACS) patients
      in different age groups and compare management provided to in-hospital outcome.
      DESIGN: Prospective multi-hospital registry. SETTING: Seventeen secondary and
      tertiary care hospitals in Saudi Arabia. PATIENTS: Five thousand and fifty-five
      patients with ACS. They were divided into four groups: ?40 years, 41-55 years, 56
      70 years and ?70 years. MAIN OUTCOME MEASURES: prevalence, utilization and
      mortality. RESULTS: Ninety-four percent of patients <40 years compared to 68% of
      patients >70 years were men. Diabetes was present in 70% of patients aged 56-70
      years. Smoking was present in 66% of those <40 years compared to 7% of patients
      >70 years. Fifty-three percent of the patients >70 years and 25% of those <40
      years had history of ischemic heart disease. Sixty percent of patients <40 years
      presented with ST elevation myocardial infarction (STEMI) while non-ST elevation
      myocardial infarction was the presentation in 49% of patients >70 years. Thirty
      four percent of patients >70 years compared to 10% of patients <40 years
      presented >12 h from symptom onset with STEMI. Fifty-four percent of patients >70
      compared to 64-71% of those <70 years had coronary angiography. Twenty-four
      percent of patients >70 compared to 34-40% of those <70 years had percutaneous
      coronary intervention. Reperfusion shortfall for STEMI was 16-18% in patients >56
      years compared to 11% in patients <40 years. Mortality was 7% in patients >70
      years compared to 1.6-3% in patients <70 years. For all comparisons (p < 0.001).
      CONCLUSIONS: Young and old ACS patients have unique risk factors and present
      differently. Older patients have higher in-hospital mortality as they are treated
      less aggressively. There is an urgent need for a national prevention program as
      well as a systematic improvement in the care for patients with ACS including a
      system of care for STEMI patients. For older patients there is a need to identify
      medical as well as social factors that influence the therapeutic management
      plans.

PMID- 23960663
TI  - Diagnostic importance of platelet parameters in patients with acute coronary
      syndrome admitted to a tertiary care hospital in southwest region, Saudi Arabia.
AB  - OBJECTIVE: Identifying risk factors for acute coronary syndrome (ACS) is
      important for both diagnostic and prognostic purposes. Abnormal platelet
      parameters, mainly platelet count (PC), mean platelet volume (MPV) and platelet
      distribution width (PDW) are thought to be among these risk factors. In this
      study, the associations between PC, MPV and PDW and ACS were investigated in
      patients admitted to the tertiary care hospital in the south west region of Saudi
      Arabia. MATERIALS AND METHODS: A retrospective cohort of 212 patients with the
      diagnosis of ACS admitted to Aseer Central Hospital during the period extending
      from February 1, 2008 to October 31, 2008 were included. The control group
      consisted of 49 matched subjects who were admitted for chest pain investigation
      and subsequently found to be non-cardiac chest pain after performing relevant
      investigations. Blood samples were taken at the time of admission for platelet
      parameters. Statistical analysis was made using SPSS software and P-values were
      considered significant if <0.05. RESULTS: A total of 212 patients with acute
      coronary syndrome (80 patients with MI and 132 patients with UA) and 49 matched
      controls were studied. The PC was not statistically different among the three
      groups (283.3 +/- 94.8 * 10(9) L(-1) for MI cases, 262 +/- 60.8 * 10(9) L(-1) for
      UA cases and 275.8 +/- 58.9 * 10(9) L(-1) for controls). The MPV was
      significantly larger in MI cases compared to controls (8.99 +/- 1.5 fl vs. 8.38
      +/- 0.51 fl, respectively, P < 0.009), similarly, the MPV was significantly
      larger in UA cases compared to controls (9.23 +/- 1.19 fl vs. 8.38 +/- 0.51 fl,
      respectively, P < 0.001). The PDW was significantly higher in MI cases compared
      to controls (15.88 +/- 1.5 fl vs. 11.96 +/- 1.8 fl, respectively, P < 0.001),
      similarly, the PDW as also significantly larger in UA cases compared to controls
      (18.1 +/- 18 fl vs. 11.96 +/- 1.8 fl, respectively, P < 0.019). CONCLUSION:
      Platelet parameters mainly MPV and PDW are readily available and relatively
      simple and inexpensive laboratory tests which we detected to be significantly
      raised in patients who have suffered an acute coronary syndrome compared with
      controls.

PMID- 23960664
TI  - Initial experience of using intracardiac echocardiography (ICE) for guiding
      balloon mitral valvuloplasty (BMV).
AB  - BACKGROUND AND AIMS: BMV is an established treatment for rheumatic mitral valve
      stenosis. The procedure is historically guided by fluoroscopy, and the role of
      intracardiac echocardiogram (ICE) guidance is not well defined. We report our
      initial experience of using ICE to guide BMV procedures. METHODS: During BMV
      procedure, ICE catheter was inserted into the right atrium from the right femoral
      vein, and the septal puncture was monitored by ICE, as well as positioning of the
      balloon in the mitral valve. Comparisons were made between ICE, transthoracic
      echocardiography (TTE), and catheterization derived hemodynamic measurements
      (cath). RESULTS: Seventeen patients with mitral stenosis underwent the procedure.
      The mean age was 44.4 +/- 21 years. The mean MV area increased from 0.9 +/- 0.1
      cm(2) to 1.7 +/- 0.2 cm(2), P < 0.0001 and the mean gradient decreased from 12.6
      +/- 5.8 mmHg to 4.9 +/- 1.8 mmHg, P < 0.001. Atrial septum puncture and guidance
      of the balloon into the MV apparatus were obtained in all patients under ICE
      guidance. Severe MR developed in one patient and was readily detected by ICE. ICE
      derived gradient measurements were comparable to those obtained by TTE, and cath.
      CONCLUSION: ICE guidance of BMV is feasible, and useful in monitoring safe septal
      puncture, optimizing balloon positioning, and in detecting complications. The
      hemodynamic measurements obtained were comparable to those obtained by TTE, and
      cath.

PMID- 23960665
TI  - Reasons for cancellation of elective cardiac surgery at Prince Sultan Cardiac
      Centre, Saudi Arabia.
AB  - The cancellation of surgery is a significant drain on health resources. However,
      a persistent problem in most hospitals is short notice cancellation of scheduled
      operations, even upto the day of surgery. In some cases, patients have been
      prepared for surgery, and the staff is assembled and expecting to operate. In UK
      8% of scheduled elective operations are cancelled within 24 hours of surgery. The
      reasons include cancellation by the patient, cancellation for poorly optimized
      medical conditions, or cancellations due to poor organization. Many of these are
      difficult to quantify. However, one relatively easily measured factor is the
      possibility that some operating lists were predictably over-booked. An operating
      list may over-run because of delayed starts, slow turnover, unanticipated
      surgical/anaesthetic problems or staff shortages. Many of these are difficult to
      quantify. BACKGROUND AND OBJECTIVE: Prince Sultan Cardiac center is one of the
      largest referral center in the Middle East and there is no published data on the
      reasons for cancellation of specifically cardiac procedures. However, an audit
      was performed to assess the reasons for the cancellation of the cases on the day
      of surgery in cardiac theatres. According to one of the studies published in an
      Australian journal the percentage of cancelled cardiothoracic cases was
      determined to be 15.8%. RESULTS: Total number of cardiac surgical patients
      including pediatric and adult during a period from June 2008 to May 2009 were
      2191. Out of those, 1681 cases were done during the study period, 510 (23.27%)
      cases were cancelled during the study period. The operation theatre was
      functional for 331 days during the study period. Cancellations done by the
      surgeons were 34% while the patient's related cancellations were 32%. The
      administrative issues contributed to 34% in overall cancellation and anaesthetist
      related cancellation were 0%. CONCLUSION: We estimated 22% of the elective
      operations which were cancelled on the day of surgery were potentially avoidable.
      There is still a need to do further research to look for the identifiable reasons
      and strategic measures to eliminate the reasons for cancellation on the day of
      surgery.

PMID- 23960666
TI  - Electrocardiographic findings in heat stroke and exhaustion: A study on Makkah
      pilgrims.
AB  - Over two million pilgrims perform annual rituals in Makkah region, which when
      coincides with summer months, exposes them to outdoor temperatures exceeding 45 
      degrees C and humidity approaching 80%. Accordingly, heat illnesses are common
      including explicit heat strokes and heat exhaustion. No previous studies
      elaborated on electrocardiographic changes among this unique cohort. OBJECTIVE:
      To compare electrocardiographic changes in three groups exposed to high outdoor
      temperatures, namely, patients with heat stroke compared to patients with heat
      exhaustion and a control group exposed to the same outdoor temperatures without
      clinical manifestations. SUBJECTS AND METHODS: Through case control design, two
      case groups of patients were selected. The first group (G1) was 34 patients
      admitted to the cooling units with clinical picture of heat stroke and the second
      group (G2) comprised 28 patients admitted with heat exhaustion. The control group
      (G3) included 31 patients selected from relatives of patients and outdoor
      workers. The outcome for comparison was 12-lead electrocardiographic changes done
      for all selected individuals. For (G1), the ECG was done while they were prepared
      for cooling or immediately when cooling was started. RESULTS: In G1, 18 were
      females and 16 males with ages of 20-76 years (59 +/- 11 years). Their heart
      rates ranged from 64 to 160 beats per minute (mean 120 +/- 24 per minute). Only
      5/34 ECGs were completely normal. Sinus tachycardia was present in 27/34 patients
      (79%), with ischemic changes in 9/34 ECGs. In G2, 24 were males and four females
      with ages of 25-80 (mean 47 +/- 15 years), the heart rate ranged from 64 to 170
      per minute (mean 97 +/- 16 per minute). Seven out of 28 ECGs were normal (25%)
      while 21/28 had some abnormalities. None had ischemic changes. Control group
      (G3), was five females and 26 males ages 18-80 years (mean 38 +/- 15 years),
      22/31 had normal ECGs (71%). All had normal sinus rhythm, 56-98 beats per minute
      (74 +/- 11). Nine patients had some electrocardiographic abnormalities but none
      had ischemic changes. CONCLUSION: We conclude that electrocardiographic
      abnormalities occur with a high frequency in patients with heat stroke and heat
      exhaustion, with sinus tachycardia and ischemic changes occurring more frequently
      in patients with heat stroke.

PMID- 23960667
TI  - The unusual hypertensive patient.
AB  - Many young patients with systemic hypertension have secondary causes which if
      identified early could lessen the cardiovascular complications associated with
      long standing hypertension. Coarctation of the aorta is one of those rare causes.
      We describe a 40 year old male with hypertension, coarctation of the aorta,
      bicuspid aortic valve, PDA and an adrenal mass. 

PMID- 23960668
TI  - Angiotensin converting enzyme inhibitor as an additive treatment after successful
      balloon dilation of a critical pulmonary valve stenosis.
AB  - A 2 days old, 2.7 kg heavy baby boy with critical pulmonary stenosis, underwent
      successful balloon dilation. After the uneventful procedure, he remained oxygen
      dependent. The baby was given oral angiotensin converting enzyme inhibitor (ACE
      inhibitor), instead of an infusion of alpha blocker. Within few hours, in the
      afternoon of the same day after administration of ACE Inhibitor, the baby could
      be weaned off oxygen, maintaining on room air, oxygen saturation between 87% and
      92%. At follow-up, two months later, his saturation was 99% on room air. We
      believe that some neonates with critical pulmonary valve stenosis who remain
      oxygen dependent despite successful balloon dilation, could benefit from such
      management. 

PMID- 23960670
TI  - Suture-less aortic valve replacement.

PMID- 23960671
TI  - Message from the Editor-in-Chief.

PMID- 23960669
TI  - Reconstruction of cavopulmonary pathway for the patient with persistent
      arteriovenous malformations due to offset flow from hepatic vein.
AB  - The hypoxemia caused by arteriovenous malformations after cavopulmonary shunt in
      patients with heterotaxy, an interrupted inferior vena cava and single ventricle
      physiology have been treated by incorporation of hepatic vein flow into the
      pulmonary circulation. However, some patients have persistent arteriovenous
      malformations because of offset hepatic venous flow to one pulmonary artery.
      Various approaches have been used to change offset flow to achieve balanced
      hepatic flow to the lungs in this patient population. This case report highlights
      the challenges that may be associated with anastomosis of the azygos vein to the
      inferior vena cava at the level of the diaphragm and illustrates an alternative
      technique to direct hepatic venous blood into an affected lung with arteriovenous
      malformations. The redirection of hepatic venous flow to the affected pulmonary
      artery resulted in resolution of symptoms within months of surgery. 

PMID- 23960672
TI  - JSHA and publication ethics.

PMID- 23960673
TI  - Gender differences in cardiovascular risk factors among adolescents in Aseer
      Region, southwestern Saudi Arabia.
AB  - OBJECTIVE: The objective of this study was to explore gender differences in the
      prevalence of silent and clinical apparent cardiovascular risk factors among
      adolescents in Aseer Region, southwestern Saudi Arabia. MATERIALS AND METHODS: A
      cross-sectional study on a stratified sample of 1869 adolescents was carried out.
      They were interviewed and examined for weight and height, systolic and diastolic
      blood pressure using standardized techniques. RESULTS: The study revealed high
      prevalence of some potential behavioral and biological cardiovascular diseases
      (CVD) risk factors among adolescent males and females in the study area.
      Behavioral risk factors included inadequate low consumption of fruits and
      vegetables, physical inactivity, and smoking. Physical inactivity was
      significantly more prevalent among females than males (42.9% and 25.7%,
      respectively). Smoking was significantly more among females than males (11.8% and
      1.3%, respectively). Biological risk factors found were family history of CVD,
      obesity and high blood pressure. Obesity was significantly prevalent among
      females (29.4%) compared to males (20.6%). Males had significantly more high
      blood pressure than females. In logistic regression analysis, being male (aOR =
      2.992, 95% CI = 1.933-4.742) and obesity (aOR = 2.995, 95% CI = 2.342-3.991) were
      found to be significant risk factors in developing high blood pressure among
      adolescents in the region. CONCLUSIONS: Presence of cardiovascular risk factors
      among adolescents is a public health problem in the region. There is a need for a
      national program in the country to prevent and control cardiovascular risk
      factors among adolescents.

PMID- 23960674
TI  - Risk modeling for ventricular assist device support in post-cardiotomy shock.
AB  - BACKGROUND: Post-cardiotomy shock (PCS) has a complex etiology. Although
      treatment with inotrops and intra-aortic balloon pump (IABP) support improves
      cardiac performance, end-organ injuries are common and lead to prolonged ICU
      stay, extended hospitalization and increased mortality. Early consideration of
      mechanical circulatory support may prevent such complications and improve
      outcome. METHODS: Between January 1997 and January 2002, 321 patients required
      IABP and inotropic support for PCS following coronary artery bypass grafting
      (CABG) at our institution. Perioperative variables including age, mixed venous
      saturation (MVO2), inotropic requirements and LV function were analyzed using
      multivariate statistical methods. All explanatory variables with a univariate p
      value <0.10 were entered into a stepwise logistic regression model to predict
      hospital mortality. Odds ratios from significant variables (p < 0.05) in the
      regression model were used to compose a risk score. RESULTS: Overall hospital
      mortality was 16%. The independent risk factors for mortality in this population
      were: MVO2 < 60% (OR = 3.2), milrinone > 0.5 MUg/kg/min (OR = 3.2), age > 75 (OR
      = 2.7), adrenaline > 0.1 MUg/kg/min (OR = 1.5). A 15-point risk score was
      developed based on the regression model. Hospital mortality in patients with a
      score >6 was 46% (n = 13/28), 3-6 was 31% (n = 9/29) and <3 was 11% (n = 29/264).
      CONCLUSIONS: A significant proportion of patients with PCS continue to face high
      mortality despite IABP and inotropic support. Advanced age, heavy inotropic
      dependency and poor oxygen delivery all predicted increased risk for death.
      Further investigation is needed to assess whether early institution of VAD
      support could improve outcome in this high-risk group of patients.

PMID- 23960675
TI  - The prognostic role of serum uric acid level in patients with acute ST elevation
      myocardial infarction.
AB  - OBJECTIVES: The role of uric acid as a prognostic factor in patients with acute
      ST elevation myocardial infarction is controversial. The purpose of this study
      was to demonstrate the relationship between serum uric acid level and mortality
      during admission period and 30-day period after admission. METHODS: We assessed
      the relation between serum uric acid level and in-hospital and short-term
      mortality rates in 184 patients admitted with acute ST elevation myocardial
      infarction. We divided the patients according to their gender and uric acid level
      measured on admission into four groups: group A1: men with uric acid ?7 mg/dl
      versus group B1: men with uric acid >7 mg/dl and group A2: women with uric acid
      ?5.6 mg/dl versus group B2: women with uric acid >5.6 mg/dl. The patients were
      followed for 30 days after admission. RESULTS: In-hospital mortality rate in
      group B1 was higher than group A1 [P value: 0.011, Relative risk: 13.33 (95%
      confidence interval: 1.55-114.7)]. Short-term all-cause mortality was
      significantly higher in group B1 patients [P value: 0.037, Relative risk: 3.3
      (95% confidence interval: 1.02-10.64)]. Multivariate logistic regression analysis
      of data showed an odds ratio of 15.23 for in-hospital mortality and odds ratio of
      3.76 for short-term mortality in male hyperuricemic patients. CONCLUSIONS: Our
      data suggest that in the acute phase of ST elevation myocardial infarction, uric
      acid has a prognostic role for in-hospital and short-term (30-day) mortality in
      men.

PMID- 23960676
TI  - Waiting time for transfer of patients with prostaglandin dependant congenital
      heart defects to tertiary cardiac centers.
AB  - Worldwide congenital heart defects (CHD) are the leading cause of infant deaths
      owing to congenital anomalies. Delay in diagnosing and operating in neonates with
      prostaglandin dependant CHD may lead to significant morbidity and mortality.
      OBJECTIVES: To assess the time interval needed for acceptance and transfer of
      patients with critical CHD to a tertiary cardiac center and the impact on the
      patient's survival. STUDY DESIGN: Retrospective database reviews of all cases
      diagnosed to have prostaglandin dependant (PG) CHD at Prince Sultan Cardiac
      Center-Qassim during a 43 months period (from May 2007 to December 2010).
      RESULTS: During the study period 104 patients were diagnosed to have PG dependant
      CHD. Patients with PG dependant systemic circulation constitute 60% of patients.
      Patients with ventricular septal defect (VSD) associated with coarctation of the
      aorta constituted 16% of patients. The mean waiting time for transfer to a
      tertiary cardiac center was 10 +/- 10 days. Twenty-two (21%) patients died while
      waiting for acceptance and transfer. Eleven patients were diagnosed with
      hypoplastic left heart syndrome (HLHS). There was no significant difference in
      the waiting time for those with or without HLHS, with a mean of 9 days for both.
      Six of our patients had infections with positive blood cultures. The mean waiting
      period for those with proved infection was 25 days compared with 8 days for those
      with no proved infection (p value < 0.005). CONCLUSION: There are a significant
      number of patients with severe CHD who die while waiting for acceptance and
      transfer to a tertiary cardiac center. The causes for delay could be the presence
      of infection, prematurity and low birth weight. The limited numbers of tertiary
      cardiac centers in Saudi Arabia as well as cardiac ICU beds are among the factors
      delaying the acceptance of patients requiring cardiac surgery.

PMID- 23960677
TI  - Relationship between HLA molecules and late restenosis after coronary stent
      placement.
AB  - OBJECTIVE: The objective of this study is to confirm whether there is relation
      between the human leucocyte antigen (HLA) locus and restenosis after percutaneous
      coronary intervention (PCI) holds in our patient population and whether it can be
      useful as a prognostic factor. METHODS: We examined the HLA phenotypes in 46
      consecutive patients (39 men, 7 women, mean age of 57 +/- 9 years) who had
      successful stent implantation in the coronary artery. Selective coronary
      arteriography was performed 6 months after coronary stenting to assess the
      presence of restenosis. The HLA phenotyping was performed for HLA-A,-B,-C
      antigens by Terasaki microlymphocytotoxicity technique and for HLA-DR alleles
      with PCR-SSP technique. RESULTS: Restenosis(R+) was present in 12 (26.1%)
      patients (11 men, 1 woman, mean age of 57 +/- 10 years). For HLA Class I antigens
      frequency of HLA-B62 and HLA-CW2 antigen was slightly higher in restenotic
      patients but did not reach statistical significance. For HLA-DR alleles
      restenotic patients had higher frequencies for HLA-DRB1(*)01(R+ %25, R- %14.7),
      and HLA-DR11(R+ %41.7, R- %20.6), without reaching statistical significance and
      lower frequencies for DR7(R+ %0, R- %17.6) and D13(R+%8.3, R- %32.4) and HLA-DR53
      (R+ %25, R- %35.3) without reaching statistical significance. CONCLUSION: In
      conclusion, results show that there was no relationship between the development
      of restenosis and HLA-subtypes.

PMID- 23960678
TI  - Ischaemic heart disease in pregnancy.
AB  - Ischaemic heart disease (IHD) in pregnancy, particularly myocardial infarction
      (MI), is a rare yet potentially fatal condition for the mother and the foetus.
      With delays in the age of conception, the changes in some social habits among
      females including cigarette and shisha smoking in addition to an increased
      prevalence of diabetes mellitus, IHD may represent a real hazard among pregnant
      women in the near future. The difficulty in the diagnosis emerges from the
      similarity of the signs and symptoms of ischaemia and infarct to some of the
      physiological adaptations that occur in a normal pregnancy. The physiological
      changes that are normal in pregnancy may aggravate pre-existing disease and may
      unmask some underlying unrecognized coronary vascular changes; therefore, the
      diagnosis requires a high index of suspicion and careful assessment of the
      underlying risk factors. The management of IHD always requires a
      multidisciplinary team approach. The management of each patient should be
      individualized according to the clinical condition, the risk factors, and the
      availability of the necessary support. Pregnancy after MI may be an acceptable
      and reasonably safe option provided the cited criteria are met. A systematic
      PubMed search was performed to identify all published data including cases
      reports, small series and systematic reviews in the existing literature. These
      publications were comprised of both retrospective and cross sectional population
      studies to maximize the number of cases considered in order to reach conclusions
      and make recommendations based on the best available evidence considering the
      rare occurrence of this event. The epidemiology, diagnosis, medical and surgical
      treatment, and prognosis of IHD in pregnancy are the subjects of the present
      review. 

PMID- 23960680
TI  - Cardiovascular disease in Hajj pilgrims.
AB  - The changing pattern of hospital admissions during Hajj, the Muslims yearly
      pilgrimage attracting millions of pilgrims from all around the globe, has
      gradually seen infectious causes of hospital admission replaced by cardiovascular
      diseases as a leading cause of both intensive care unit admission and death.
      While this trend is partly associated with the high quality of medical services
      and awareness programs targeted at reducing the spread of infections, at the same
      time it underscores an urgent need to establish a pragmatic system to manage the
      challenge of cardiovascular morbidities and mortality during Hajj. SEARCH
      STRATEGY AND INCLUSION CRITERIA: A PubMed Central (PMC) literature search without
      date restrictions was performed for articles reporting on the medical experience
      during Hajj. There were 109 articles were returned using "Hajj" and "mortality"
      as search terms. After determining relevance to the current theme based on both
      direct and indirect reference to the pattern hospital admission during Hajj, 20
      articles reporting on conducted studies were obtained. Data from these studies
      reporting on the pattern and outcome of hospitalization during Hajj were examined
      and helped in arriving at the conclusions presented in this review.

PMID- 23960681
TI  - Use of microvena snare catheter in non-ST elevation myocardial infarction due to
      saphenous vein graft occlusive thrombi.
AB  - A 75-year-old man presented with acute coronary syndrome; he had a saphenous vein
      graft thrombosis. Percutaneous coronary intervention of bypass graft vessels is
      more challenging due to a higher incidence of periprocedural distal micro
      emobilization and myocardial infarction. Current guidelines for percutaneous
      coronary intervention advocate the use of distal embolic protection devices,
      especially in patients with large thrombus burden, undergoing percutaneous
      intervention for vein graft disease. This patient was treated by manual
      aspiration of graft thrombus using a microvena catheter and successful clot
      removal was achieved. There are yet no best available therapeutic options for
      patients undergoing percutaneous coronary intervention of saphenous vein graft
      lesions. 

PMID- 23960682
TI  - The ECG role in identifying the etiology of tachycardia-induced cardiomyopathy
      (TIC).
AB  - Tachycardia-induced cardiomyopathy (TIC) is a well recognized entity of heart
      failure (HF) and various mechanisms due to tachyarrhythmias have been postulated
      to be responsible for impaired cardiac contractility. Previously reported cases
      showed reversibility of such disorders whenever stable cardiac rhythm is
      maintained adequately and we report on a 16-year-old boy who has been diagnosed
      to have TIC, which was misinterpreted initially as sinus tachycardia secondary to
      dilated cardiomyopathy and heart failure. A complete recovery of his left
      ventricular function was achieved by radiofrequency catheter ablation and
      highlights the importance of a 12-lead electrocardiogram (ECG) assessment in such
      patients. 

PMID- 23960683
TI  - Hypoplastic left heart syndrome, cor triatriatum and partial anomalous pulmonary
      venous connection: Imaging of a very rare association.
AB  - A newborn is presented with an association of hypoplastic left heart syndrome,
      cor triatriatum and partial anomalous pulmonary venous connection. The diagnosis
      was established with echocardiography and further confirmed with computed
      tomography. To our knowledge the images of such an association have never been
      reported before. 

PMID- 23960684
TI  - Simultaneous endovascular stent and renal stent placement for acute type B aortic
      dissection with malperfusion of kidney.
AB  - Acute aortic dissection frequently causes life-threatening organ ischemia. The
      optimal therapy for acute type-B aortic dissection is still controversial.
      Surgery for acute dissection with organ malperfusion is known to carry a high
      morbidity and mortality; however endovascular treatment is becoming an
      alternative form of treatment. We report a clinical case of emergency
      percutaneous thoracal aorta endovascular stenting and renal artery stenting in a
      patient who had renal malperfusion and acute renal failure due to acute type-B
      dissection. The present case is a fundamental examples of collaboration between
      the cardiologist and cardiovascular surgeon in a hybrid procedure. 

PMID- 23960685
TI  - Letter in response to the original article: "Evaluation of femoral approach to
      coronary sinus catheterisation in electrophysiological and ablation procedures:
      Single centre experience" authored by Osama Abdel Atty, Mohamed Morsy and Mark M.
      Gallagher (Journal of the Saudi Heart Association, Volume 23, Issue 4, October
      2011, pp. 213-216).

PMID- 23960686
TI  - Response to Letter by: Chase, doi: 10.1016/j.jsha.2012.01.001.

PMID- 23960679
TI  - Diastolic dysfunction and heart failure with a preserved ejection fraction:
      Relevance in critical illness and anaesthesia.
AB  - Epidemiological and clinical studies suggest that HF with a preserved ejection
      fraction will become the more common form of HF which clinicians will encounter.
      The spectrum of diastolic disease extends from the asymptomatic phase to
      fulminant cardiac failure. These patients are commonly encountered in operating
      rooms and critical care units. A clearer understanding of the underlying
      pathophysiology and clinical implications of HF with a preserved ejection
      fraction is fundamental to directing further research and to evaluate
      interventions. This review highlights the impact of diastolic dysfunction and HF
      with a preserved ejection fraction during the perioperative period and during
      critical illness. 

PMID- 23960687
TI  - Transcatheter Aortic Valve Implantation (core valve) prosthesis complicated by
      mitral stenosis.
AB  - A 90 year-old male patient, known to have severe aortic stenosis (AS), was
      admitted with chest pain, shortness of breath and swelling of both lower limbs.
      He had history of ischemic heart disease and percutaneous coronary intervention
      (PCI) of left anterior descending artery (LAD) in 2002. He also had long standing
      hypertension, primary hypothyroidism and hypercalcemia. He had a permanent
      pacemaker, chronic gastritis, gastrointestinal bleeding and bilateral knee
      osteoarthritis in 2007. Patient was treated medically for his heart failure
      symptoms. Transthoracic echocardiogram (TTE) showed normal ejection fraction >55%
      and severe aortic stenosis, aortic valve area 0.58 cm(2), mean G 64 mmHg and peak
      gradient of 118 mm Hg. In November 2010 the patient was evaluated for the
      transcatheter aortic valve implantation (TAVI) program after a multidisciplinary
      evaluation. His predicted Euro Score was 28% and both risk and benefits were
      explained to the family. A 29 mm core valve prosthesis was deployed. The TTE 4
      days later showed mitral valve (MV) area = 2.04 cm(2) and MG across MV = 6 mm Hg.
      Impingement of anterior mitral valve leaflet (AMVL) by the inflow portion of core
      valve prosthesis led to mild mitral stenosis (MS). TEE is a helpful tool to
      diagnose this phenomenon. 

PMID- 23960688
TI  - Message from the Editor-in-Chief.

PMID- 23960689
TI  - Effects of a preoperative individualized exercise program on selected recovery
      variables for cardiac surgery patients: A pilot study.
AB  - OBJECTIVE: Research on preoperative individualized exercise prescription (PIEP)
      for heart surgery patients in Taiwan is lacking. Thus, the purpose of this study
      was to examine the feasibility of a PIEP in the Taiwanese population. METHOD: A
      quasi-experimental design, using purposive sampling, was conducted. Thirty-five
      patients were recruited, of whom 15 chose to participate in the experimental
      (PIEP training plus usual care) group, and 20 chose to participate in the control
      (usual care) group. The effects of the intervention were determined by pulmonary
      complication-related parameters and quality of life. RESULTS AND CONCLUSION: The
      development and process of PIEPs suitable for cardiac patients was described in
      this study. The results reveal that the two-week exercise-training program
      contributed to a decreased peak respiratory exchange ratio (RER) after the
      surgery and earlier ambulation. The effectiveness of PIEPs in improving the
      quality of life in cardiac surgery patients was validated. This study may also
      contribute as a reference of the PIEP effect on patients to the healthcare
      providers.

PMID- 23960690
TI  - Outcome of tracheostomy after pediatric cardiac surgery.
AB  - OBJECTIVE: To investigate the incidence, timing indications and outcome of
      tracheotomy in children who underwent cardiac surgeries. METHODS: All pediatric
      cardiac patients (under 14 years of age) who underwent cardiac surgeries and
      required tracheotomy from November 2000 to November 2010 were reviewed. The data
      were collected and reviewed retrospectively. RESULTS: Sixteen children underwent
      tracheotomy after cardiac surgery. Fifteen of these cases had surgery for
      congenital heart disease, and one had surgery for an acquired rheumatic mitral
      valve disease. The mean +/- SEMs of the durations of ventilation before and after
      tracheotomy were 60.4 +/- 9.8 and 14.5 +/- 4.79 days respectively (P value
      0.0002). The means +/- SEM of the lengths of ICU stay before and after
      tracheotomy were 63.31 +/- 10.15 and 22 +/- 5.4 days respectively (P value
      0.0012). After the tracheotomy 12/16 patients (75%) were weaned from their
      ventilators and 10/16 were discharged from the PCICU. Six patients were
      discharged from the hospital and 3 were successfully decannulated. The overall
      survival rate was 9/16 (56%). CONCLUSION: Tracheostomy shortens the duration of
      mechanical ventilation and facilitates discharge from the ICU. The mortality of
      tracheotomy patients is still significant but is mainly related to the primary
      cardiac disease.

PMID- 23960691
TI  - Clinical presentation and short-term outcome of acute coronary syndrome in native
      young Saudi population.
AB  - OBJECTIVES: To investigate acute coronary syndromes (ACS) in the young Saudi
      population in Aseer Region, southwestern Saudi Arabia. MATERIALS AND METHODS: We
      retrospectively reviewed our database between January 2006 and May 2009, 924
      patients were diagnosed to have ACS. Among them 107 patients (11.6%) met our
      definition of young [66 (61.7%) male < 45 years, and 41 (38.3%) female < 55
      years]. We compared this study population to a control group of 50 elderly
      patients consecutively enrolled in a contemporary period. RESULTS: The overall
      age was 42.3 +/- 7.9 and 68.7 +/- 10.1 years in the study population and control
      respectively. 100% of the population and 92% of the control group presented with
      chest pain. Diabetes mellitus (DM) prevalence was 46.7% in the study population
      (63.4% in females), and 62% in the control group. Hypertension, smoking,
      dyslipidemia and overweight/obesity were reported in 31.8%, 25.2%, 21.5% and
      44.9% of the study population and 58%, 6%, 26% and 42% of the control group,
      respectively. Past history of coronary artery disease was documented in 16.8% of
      the study population and 38% of the control group. The discharge diagnoses were
      ST-segment elevation myocardial infarction (STEMI) in 41 (38.3%) (representing
      4.4% of the whole ACS population) and 11 (22%) patients of the study population
      and control group respectively, non-ST-segment elevation myocardial infarction in
      36 (33.6%) and 23 (46%) patients of the study population and control group,
      respectively, and unstable angina in 30 (28.0%) and 15 (30%) patients of the
      study population and control group, respectively. Coronary angiography was
      performed in 86 (80.4%) and 41 (82%) patients in the study population and control
      group respectively. In hospital, one young patient had acute ischemic stroke and
      one elderly patient died, 22.4% of the study population and 32% of control group
      were discharged with clinical diagnosis of heart failure or in need for
      diuretics. CONCLUSION: In our study, the young Saudi population with ACS had
      chest pain as the leading symptom. STEMI was the major final diagnosis and among
      one of the highest reported worldwide. There is a high prevalence of DM; however,
      they have favorable in hospital and short-term outcome.

PMID- 23960692
TI  - Visualization of patent ductus arteriosus using real-time three-dimensional
      echocardiogram: Comparative study with 2D echocardiogram and angiography.
AB  - PURPOSE: To determine the feasibility and accuracy of real time 3D
      echocardiography (RT3DE) in determining the dimensions and anatomical type of the
      patent ductus arteriosus (PDA). METHODS: The study included 42 pediatric patients
      with a mean age of 3.6 years (ranging from 2 months to 14 years) who were
      referred for elective percutaneous PDA closure. All patients underwent full 2D
      echocardiogram as well as RT3DE with off line analysis using Q lab software
      within 6 h from their angiograms. The PDA was studied as regard the anatomical
      type, length of the duct as well as the ampulla and the pulmonary end of the PDA.
      Data obtained by RT3DE was compared against 2D echocardiogram and the gold
      standard angiography. RESULTS: Offline analysis of the PDA was feasible in 97.6%
      of the cases while determination of the anatomical type using gated color flow 3D
      acquisitions was achieved in 78.5% of the cases. The pulmonary end of the duct
      was rather elliptical using 3D echocardiogram. There was significant difference
      between the pulmonary end measured by 3D echocardiogram and angiography (P <
      0.001). There was no significant difference between either the length or the
      ampulla of the PDA measured by 3D echocardiogram and that measured by angiography
      (P value = 0.325 and 0.611, respectively). There was a good agreement between
      both 2D or 3D echocardiogram and angiography in determining the anatomical type
      of the PDA (K = 0.744 and 0.773, respectively). However 3D echocardiogram could
      more accurately determine type A and type E ductus compared to 2D echocardiogram.
      CONCLUSION: 3D echocardiogram was more accurate than 2D echocardiogram in
      determining the length and the ampulla of the PDA. The morphologic assessment of
      the PDA using gated 3D color flow was achieved in 78.5% of the patients.
      Nevertheless the use of 3D echocardiogram in assessment of small vascular
      structures like PDA in children with rapid heart rates is still of limited
      clinical value.

PMID- 23960693
TI  - Ultrasonography assessment of vocal cords mobility in children after cardiac
      surgery.
AB  - OBJECTIVES: Upper airway obstruction after pediatric cardiac surgery is not
      uncommon. In the cardiac surgical population, an important etiology is vocal cord
      paresis or paralysis following extubation. In this study, we aimed to evaluate
      the feasibility and accuracy of ultrasonography (US) assessment of the vocal
      cords mobility and compare it to fiber-optic laryngoscope (FL). MATERIAL AND
      METHODS: A prospective pilot study has been conducted in Pediatric Cardiac ICU
      (PCICU) at King Abdulaziz Cardiac Center (KACC) from the 1st of June 2009 till
      the end of July 2010. Patients who had cardiac surgery manifested with
      significant signs of upper airway obstruction were included. Each procedure was
      performed by different operators who were blinded to each other report. Results
      of invasive (FL) and non-invasive ultrasonography (US) investigations were
      compared. RESULTS: Ten patients developed persistent significant upper airway
      obstruction after cardiac surgery were included in the study. Their mean +/- SEM
      of weight and age were 4.6 +/- 0.4 kg and 126.4 +/- 51.4 days, respectively. All
      patients were referred to bedside US screening for vocal cord mobility. The
      results of US were compared subsequently with FL findings. Results were identical
      in nine (90%) patients and partially different in one (10%). Six patients showed
      abnormal glottal movement while the other four patients demonstrated normal vocal
      cords mobility by FL. Sensitivity of US was 100% and specificity of 80%.
      CONCLUSION: US assessment of vocal cord is simple, non-invasive and reliable tool
      to assess vocal cords mobility in the critical care settings. This screening tool
      requires skills that can be easily obtained.

PMID- 23960694
TI  - Coronary anomaly with a left ventricular accessory chamber: Is it left
      ventricular aneurysm or diverticulum?
AB  - A 60-year-old male hypertensive was suspected to have post myocardial infarction
      left ventricular aneurysm. His transthoracic echocardiogram performed elsewhere
      reported an inferior wall left ventricular aneurysm. He was referred for coronary
      angiography. His coronary angiogram and repeat transthoracic echocardiogram
      demonstrated an accessory chamber arising from mid-inferior wall synchronously
      contracting with the left ventricle suggesting a diverticulum. In addition, he
      had anomalous coronary arteries with coronary artery disease. His
      electrocardiogram did not reveal any features suggestive of a post infarct
      aneurysm. This case illustrates the importance of a comprehensive clinical and
      echocardiographic examination with a broad differential thought process. 

PMID- 23960695
TI  - Successful management of fungal pericarditis and endocarditis in a neonate: A
      case report.
AB  - Neonatal fungal endocarditis is a rare but serious infection, which does not have
      a well-accepted management method. This is the second report of this condition in
      Saudi Arabia. A preterm, very low birth weight, female neonate presented with
      fever and shortness of breath. An echocardiogram showed moderate pericardial
      effusion and two masses in the heart, one in the right ventricle and the other in
      the inferior portion of the posterior mitral valve of the left ventricle. Blood
      and pericardial fluid cultures revealed an infection with Candida albicans. The
      patient received a 60 days course of intravenous fluconazole and amphotericin B
      lipid complex. At the conclusion of treatment, she was discharged in good
      condition with no echocardiographic evidence of pericardial effusion or fungal
      vegetations. Thus, a successful outcome to a serious case of fungal endocarditis
      was achieved through aggressive antifungal therapy with intravenous fluconazole
      and amphotericin B lipid complex. 

PMID- 23960696
TI  - Pseudoaneurysm of mitro-aortic intervalvular fibrosa during the course of mitral
      valve endocarditis with aorto-left ventricle outflow tract fistula.
AB  - The mitro-aortic intervalvular fibrosa (MAIVF) connects the anterior mitral
      leaflet to the posterior portion of the aortic annulus. The pseudoaneurysm of
      MAIVF is one of the uncommon but catastrophic complications of native or
      prosthetic aortic valve endocarditis or chest trauma. We report a case of
      infective endocarditis of mitral valve complicated by development of
      pseudoaneurysm of MAIVF, and fistulous formation causing massive shunt flow from
      the ascending aorta above the non-coronary cusp to the left ventricle outflow
      tract. 

PMID- 23960697
TI  - Caseous mitral annular calcification: Is it a benign condition?
AB  - Caseous mitral annular calcification (CMAC) is a variant of mitral annular
      calcification (MAC) with a central liquefaction necrosis. The echocardiographic
      prevalence of CMAC is approximately 0.6% in patients with MAC and 0.06-0.07% in
      large series of patients of all ages. However, the prevalence in necropsy series
      has been reported to be 2.7%, which indicates that this condition is yet under
      recognized. Furthermore CMAC is probably underappreciated as a source of
      potentially serious conditions. We report a case of recent stroke associated with
      CMAC diagnosed by trans-thoracic and confirmed by trans-esophageal echocardiogram
      (TEE). The importance of correct diagnosis of CMAC extends beyond the possible
      complications; since several misdiagnoses of CMAC as abscesses and cardiac tumors
      have been reported leading to inappropriate interventions. 

PMID- 23960698
TI  - The fate of post-myocardial infarction thrombi.
AB  - We are reporting a patient who sustained a large myocardial infarction with large
      kissing thrombi in echocardiogram that disappeared within 1 month without the
      administration of thrombolytic, anticoagulation or antiplatelet therapy. The
      patient did not manifest any embolic events. This unusual course calls for
      specific studies on the natural history of thrombi post myocardial infarction and
      the best modality to treat such thrombi. 

PMID- 23960699
TI  - Pulmonary metastatic leiomyosarcoma invading the left atrium through the
      pulmonary veins.

PMID- 23960700
TI  - G. Heiner sell distingushed lecture: american spinal injury association (Asia)
      40th anniversary: beginnings, accomplishments and future challenges.

PMID- 23960701
TI  - Baseline prevalence of heart diseases, hypertension, diabetes, and obesity in
      persons with acute traumatic spinal cord injury: potential threats in the
      recovery trajectory.
AB  - BACKGROUND: Chronic diseases impede the recovery trajectory of acutely injured
      persons with traumatic spinal cord injury (TSCI). This study compares the odds of
      prevalent heart disease, hypertension, diabetes mellitus, and obesity between
      persons with TSCI and persons with lower extremity fractures (LEF) who were
      discharged from acute care facilities. METHODS: 1,776 patients with acute TSCI
      (cases) and 1,780 randomly selected patients with LEF (controls) discharged from
      January 1, 1998, through December 31, 2009, from all nonfederal hospitals were
      identified. Data extracted from uniform billing files were compared between cases
      and controls in a multivariable logistic regression model controlling for
      sociodemographic and clinical covariables. RESULTS: Thirty percent of patients
      with acute TSCI had at least 1 of 4 conditions compared with 18% of patients with
      LEF (P < .0001). Persons with acute TSCI were 4 times more likely (odds ratio
      [OR], 4.05; 95% CI, 1.65-9.97) to have obesity, 2.7 times more likely to have
      heart disease (P < .001), 2 times more likely to have hypertension (P < .001),
      and 1.7 times more likely to have diabetes (P = .044) at the onset of TSCI.
      Disproportionately more Blacks than Whites have TSCI and chronic diseases.
      CONCLUSION: This study suggests that there is an increased burden of
      cardiovascular and cardiometabolic diseases among persons with acute TSCI
      compared with LEF trauma controls. Unattended comorbid conditions will affect
      quality of life and the recovery process. This warrants continuous monitoring and
      management of chronic diseases during the rehabilitation process.

PMID- 23960702
TI  - Cardiometabolic risk clustering in spinal cord injury: results of exploratory
      factor analysis.
AB  - BACKGROUND: Evidence suggests an elevated prevalence of cardiometabolic risks
      among persons with spinal cord injury (SCI); however, the unique clustering of
      risk factors in this population has not been fully explored. OBJECTIVE: The
      purpose of this study was to describe unique clustering of cardiometabolic risk
      factors differentiated by level of injury. METHODS: One hundred twenty-one
      subjects (mean 37 +/- 12 years; range, 18-73) with chronic C5 to T12 motor
      complete SCI were studied. Assessments included medical histories,
      anthropometrics and blood pressure, and fasting serum lipids, glucose, insulin,
      and hemoglobin A1c (HbA1c). RESULTS: The most common cardiometabolic risk factors
      were overweight/obesity, high levels of low-density lipoprotein (LDL-C), and low
      levels of high-density lipoprotein (HDL-C). Risk clustering was found in 76.9% of
      the population. Exploratory principal component factor analysis using varimax
      rotation revealed a 3-factor model in persons with paraplegia (65.4% variance)
      and a 4-factor solution in persons with tetraplegia (73.3% variance). The
      differences between groups were emphasized by the varied composition of the
      extracted factors: Lipid Profile A (total cholesterol [TC] and LDL-C), Body Mass
      Hypertension Profile (body mass index [BMI], systolic blood pressure [SBP], and
      fasting insulin [FI]); Glycemic Profile (fasting glucose and HbA1c), and Lipid
      Profile B (TG and HDL-C). BMI and SBP formed a separate factor only in persons
      with tetraplegia. CONCLUSIONS: Although the majority of the population with SCI
      has risk clustering, the composition of the risk clusters may be dependent on
      level of injury, based on a factor analysis group comparison. This is clinically
      plausible and relevant as tetraplegics tend to be hypo- to normotensive and more
      sedentary, resulting in lower HDL-C and a greater propensity toward impaired
      carbohydrate metabolism.

PMID- 23960703
TI  - Rehabilitation of patients with nontraumatic spinal cord injury in the
      Netherlands: etiology, length of stay, and functional outcome.
AB  - BACKGROUND: Patients with nontraumatic spinal cord injury (NTSCI) are different
      from patients with traumatic spinal cord injury. A better understanding of the
      characteristics of NTSCI and their influence on length of stay (LOS) and
      functional outcome might help professionals in planning rehabilitation and
      predicting outcomes in NTSCI. OBJECTIVE: To describe personal and injury
      characteristics, etiology, LOS, and functional outcome after inpatient
      rehabilitation in patients with NTSCI. METHODS: Retrospective single-center study
      including 124 patients who were discharged between 2006 and 2010 from their
      initial inpatient rehabilitation after onset of NTSCI. Information about personal
      and injury characteristics, LOS, and functional outcome was collected from
      medical files. Descriptive statistics were performed, and associations between
      etiology, LOS, and functional outcome were investigated. RESULTS: Fifty percent
      of participants were male, and mean age was 54.9 years (SD 13.7). Most lesions
      were classified as American Spinal Injury Association Impairment Scale (AIS) D
      (68.8%) and paraplegic (76.6%). The most frequent etiologies were degeneration
      (25.8%), vascular disease (21.8%), benign tumor (16.1%), and malignant tumor
      (15.3%). Discharge destination was usually a private residence (84.6%). Median
      LOS in inpatient rehabilitation was 61.0 days (interquartile range [IQR], 38.3
      111.8). Median functional status score was 47.5 (IQR, 30-70) at admission and 90
      (IQR, 75-100) at discharge. Etiology was a significant predictor of LOS and
      functional status at admission and discharge, but not of functional improvement
      during inpatient rehabilitation. CONCLUSION: Spinal degeneration, tumor, and
      vascular disease were the most common causes of NTSCI. All etiology groups
      improved during inpatient rehabilitation.

PMID- 23960704
TI  - Perceptions of gain following spinal cord injury: a qualitative analysis.
AB  - BACKGROUND: Significant research has focused on psychological difficulties
      following spinal cord injury (SCI), and there is a small prevalence of
      individuals who experience distress after injury. However, the converse is that
      many adjust well to injury and rate their quality of life highly. Despite this,
      there has been a comparative dearth of research investigating positive
      psychological outcomes after SCI, perceived by individuals living with this
      disability. OBJECTIVE: To explore individuals' perceptions of gain following the
      experience of SCI. METHODS: Participants, who had sustained an SCI between the
      ages 16 and 83, responded to an open-ended written question: "What do you think
      you have gained from the experience of spinal cord injury?" This was administered
      at 4 time points post injury: 6 weeks, 12 weeks, 1 year, and 2 years. RESULTS:
      Participants' responses were analyzed qualitatively using the framework of
      thematic analysis. Thirteen themes were identified: relationships, appreciation
      of relationships, perspective and appreciation of life, new goals or priorities,
      understanding of SCI or disability, appreciation of health or health care,
      changed personality, opportunity or challenge, knowledge of SCI or body, newly
      acquired skills, spirituality, acceptance, and nothing. Descriptive statistics
      were incorporated in the presentation of the data. CONCLUSIONS: This study
      provides evidence that a broad range of positive as well as negative
      psychological outcomes are possible following SCI. More research is needed to
      better understand the process through which these outcomes arise and to inform
      how such outcomes may be communicated to persons experiencing this type of
      injury.

PMID- 23960705
TI  - Review: indications for interventional radiology in the management of patients
      with spinal cord injuries.
AB  - OBJECTIVES: To outline a range of minimally invasive image-guided procedures that
      benefit spinal cord-injured patients and may expedite clinical care. STUDY
      DESIGN: Pictorial review. RESULTS/CONCLUSIONS: Image-guided procedures have made
      a significant impact in medical management in many specialties. These techniques
      continue to evolve rapidly and afford opportunities to reduce patient morbidity
      and in-patient length of stay.

PMID- 23960706
TI  - Seat pressure changes after eight weeks of functional electrical stimulation
      cycling: a pilot study.
AB  - BACKGROUND: Pressure ulcers (PUs) are a common secondary condition associated
      with spinal cord injury (SCI). PUs can potentially interfere with activities of
      daily living, occupational duties, and rehabilitation programs, and in severe
      cases they may threaten life. Functional electrical stimulation (FES) cycling has
      been proposed as an activity that may decrease the risk of PUs through the
      promotion of increased blood flow and thickening of the gluteus maximus. The
      purpose of this pilot study was to measure the effects of home-based FES cycling
      on the average and maximal seat pressure of wheelchair-reliant individuals with
      SCI. METHOD: Eight male veterans with C5-T6 SCI participated in FES cycling 3
      times per week. Cycling parameters were individualized depending on the comfort
      of the participants and the amount of current needed to perform the cycling
      activity. Pressure mapping was completed immediately before and after the 8 weeks
      of FES cycling with the measurement performed by a force sensitive application
      (FSA) 4 pressure mapping system. RESULTS: The mean average seat pressure
      decreased by 3.69 +/- 4.46 mm Hg (35.57 +/- 11.99 to 31.88 +/- 13.02), while the
      mean maximum seat pressure decreased by 14.56 +/-18.45 mm Hg (112 +/- 34.73 to
      98.36 +/- 25.89). Although neither measurement was statistically significant,
      there was a strong trend toward a reduction in average and maximal seat pressure
      (P = .052 and P = .061, respectively). CONCLUSION: The positive trend of
      decreased seat pressure in our study creates incentive for further investigation
      of the effects of electrical stimulation activities on seat pressure and the
      prevention of PUs.

PMID- 23960707
TI  - Calorie and protein intake in acute rehabilitation inpatients with traumatic
      spinal cord injury versus other diagnoses.
AB  - BACKGROUND: Obesity and its consequences affect patients with spinal cord injury
      (SCI). There is a paucity of data with regard to the dietary intake patterns of
      patients with SCI in the acute inpatient rehabilitation setting. Our hypothesis
      is that acute rehabilitation inpatients with SCI consume significantly more
      calories and protein than other inpatient rehabilitation diagnoses. OBJECTIVE: To
      compare calorie and protein intake in patients with new SCI versus other
      diagnoses (new traumatic brain injury [TBI], new stroke, and Parkinson's disease
      [PD]) in the acute inpatient rehabilitation setting. METHODS: The intake of 78
      acute rehabilitation inpatients was recorded by registered dieticians utilizing
      once-weekly calorie and protein intake calculations. RESULTS: Mean +/- SD calorie
      intake (kcal) for the SCI, TBI, stroke, and PD groups was 1,967.9 +/- 611.6,
      1,546.8 +/- 352.3, 1,459.7 +/- 443.2, and 1,459.4 +/- 434.6, respectively. ANOVA
      revealed a significant overall group difference, F(3, 74) = 4.74, P = .004. Mean
      +/- SD protein intake (g) for the SCI, TBI, stroke, and PD groups was 71.5 +/-
      25.0, 61.1 +/- 12.8, 57.6 +/- 16.6, and 55.1 +/- 19.1, respectively. ANOVA did
      not reveal an overall group difference, F(3, 74) = 2.50, P = .066. CONCLUSIONS:
      Given the diet-related comorbidities and energy balance abnormalities associated
      with SCI, combined with the intake levels demonstrated in this study, education
      with regard to appropriate calorie intake in patients with SCI should be given in
      the acute inpatient rehabilitation setting.

PMID- 23960708
TI  - Intersection syndrome in a handcyclist: case report and literature review.
AB  - Intersection syndrome describes a rare inflammatory condition located at the
      crossing point between the first dorsal compartment muscles and the radial wrist
      extensor muscles. It is a repetitive motion injury that affects patients who
      overuse their wrists. The present report reviews the incidence of the condition
      as well as the special populations it affects. The anatomy of the wrist is
      presented and clinical findings and physical examination techniques are reviewed
      to help the reader reach a quick but correct diagnosis. Finally, the most
      appropriate treatment approach is presented, incorporating rehabilitative methods
      designed to ensure a full and prompt functional recovery and resumption of
      physical activity. 

PMID- 23960709
TI  - An insight into the possible protective effect of pyrrolidine dithiocarbamate
      against lipopolysaccharide-induced oxidative stress and acute hepatic injury in
      rats.
AB  - Lipopolysaccharide (LPS) is a major cell wall molecule of Gram-negative bacteria
      known to stimulate the synthesis and secretion of several toxic metabolites, such
      as reactive oxygen species. In this study, the effect of pyrrolidine
      dithiocarbamate (PDTC), an antioxidant with nuclear factor-kappaB inhibitor
      activity, was evaluated in LPS-induced oxidative stress and acute hepatic injury
      in rats. Animals were pretreated for 3 consecutive days with PDTC (200 mg/kg/day,
      i.p.) or saline and animals were then challenged with LPS (6 mg/kg, i.p.) or
      saline. Six hours after LPS injection, animals were decapitated and blood and
      liver samples were collected to assess the chosen biochemical parameters. Saline
      pretreated animals challenged with LPS revealed extensive liver damage, as
      evidenced by increases in serum levels of alanine aminotransferase (ALT),
      aspartate aminotransferase (AST) and gamma glutamyl transferase (gamma-GT). Also,
      LPS treatment resulted in significant increases in serum lactate dehydrogenase
      (LDH), tumor necrosis factor-alpha (TNF-alpha) and nitrite levels. Furthermore,
      LPS challenge caused oxidative stress as indicated by an increase in hepatic
      lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS)
      and a decrease in hepatic reduced glutathione concentration (GSH) as well as
      decreased activities of superoxide dismutase (SOD) and catalase in hepatic
      tissues. The administration of PDTC prior to LPS challenge resulted in improved
      liver functions as evidenced by the decline in serum AST, ALT, gamma-GT levels
      and reduction in serum LDH, TNF-alpha and nitrite levels. Moreover, PDTC reduced
      the chosen lipid peroxidation marker, TBARS and increased GSH concentration, and
      SOD and catalase activities in hepatic tissues. These results indicate that PDTC
      may be a useful pharmacological agent in alleviating LPS-induced oxidative stress
      and acute hepatic injury. 

PMID- 23960710
TI  - Dereplication of bioactive constituents of the genus hypericum using LC-(+,-)-ESI
      MS and LC-PDA techniques: Hypericum triquterifolium as a case study.
AB  - Utilizing liquid chromatography-electro spray ionization-mass spectrometry (LC
      (+,-)-ESI-MS) and liquid chromatography-photodiode array detection (LC-PDA)
      techniques, a dereplication strategy for the analysis of the secondary
      metabolites constituents of the genus Hypericum has been developed. From the
      crude methanolic extract of the aerial parts of H. triquetrifolium (leaves,
      stems, and flowers) and on the basis of their UV-profiles, chromatographic
      retention times and (+,-)-ESI-MS (TIC and SIM) mass spectral data, seven known (1
      7) compounds were dereplicated fairly rapidly. The compounds were classified into
      three structural classes: phloroglucinols: hyperfirin and adhyperfirin;
      naphthodianthrones: hypericin, pseudo-hypericin, proto-hypericin, and protopseudo
      hypericin; and the flavonoid rutin. 

PMID- 23960711
TI  - Preparation and comparative evaluation of sustained release metoclopramide
      hydrochloride matrix tablets.
AB  - Metoclopramide hydrochloride (MCP) is commonly used for the management of
      gastrointestinal disorders. Frequent administration and the undesired side
      effects (extra pyramidal symptoms) of the drug on the central nervous system due
      to the fluctuations of its plasma concentrations may lead to patient
      incompliance, and hence, improper therapy. Therefore, the present work will be
      devoted to formulate the drug in sustained release formulations. MCP was
      incorporated in 12 formulae containing different polymers and/or different
      polymer ratios. These polymers were hydroxypropylmethyl cellulose (HPMC),
      carboxymethylcellulose (CMC) and ethyl cellulose (EC). Sodium starch glycolate
      (SSG) was added to some formulae in different amounts in order to soften and/or
      disintegrate the tablets. Both direct compression and granulation techniques were
      used to prepare the tablets. The physical properties were found to be
      satisfactory for all the formulae. The dissolution profiles of the tablets were
      constructed using the change-over method. The drug release involved a combination
      of both diffusion and polymer-chain relaxation mechanisms. The time required to
      release 50% of MCP ranged from 1.2 to more than 8 h. Direct compression and dry
      granulation techniques produced sufficient sustaining of the drug release.
      However, the pellets made by wet granulation released MCP in about 2 h, i.e.,
      pelletization spheronization technique was not effective in sustaining the drug. 

PMID- 23960712
TI  - A new spectrophotometric method for the determination of methyldopa.
AB  - A new, simple and low cost spectrophotometric method for the determination of
      methyldopa in pharmaceutical preparations was developed. The method was based on
      the coupling of methyldopa with 2,6-dichloroquinone-4-chlorimide (DCQ). The
      absorbance maximum (lambda max) of the resulted colored product was at 400 nm.
      Different buffers were used to determine the optimal pH for the reaction. About
      1% w/v acetate buffer with pH 8.0 gave the optimal pH required for the reaction.
      Of the different solvents tried, water and ethanol were found to be the most
      suitable solvents. Beer's law was obeyed in concentration range of 4-20 MUg/ml
      methyldopa. The correlation coefficient was found to be (r = 0.9975). The limit
      of detection and limit of quantification were 1.1 MUg/ml and 3.21 MUg/ml,
      respectively. The reaction ratio between methyldopa and DCQ was studied and found
      to be 1:3. The work included the study of the possible interference of
      hydrochlorothiazide found in combination with methyldopa tablets. The method was
      validated and results obtained for the assay of two different brands of
      methyldopa tablets were compared with the BP method (colorimetric). The
      repeatability and reproducibility of the developed method were evaluated and the
      obtained results quoted. The derivative formed as a result of the reaction of
      methyldopa with DCQ was isolated and its possible mechanistic pathway was
      suggested. 

PMID- 23960713
TI  - Two new imidazole alkaloids from Leucetta chagosensis sponge.
AB  - Chemical investigation of the sponge Leucetta chagosensis, has led to the
      isolation of two new imidazole alkaloids, methyldorimidazole (1), preclathridine
      B (2) along with the known compounds naamine E (3) and leucettamine C (4). The
      structures of the newly compounds (1 and 2) were elucidated by employing
      spectroscopic techniques ((1)H NMR, MS and UV). The structures of the known
      compounds 3 and 4 were determined by comparison of their (1)H NMR and Mass
      spectroscopic data with published values. 

PMID- 23960714
TI  - Antioxidant and hepatoprotective activity of Cordia macleodii leaves.
AB  - This investigation was undertaken to evaluate ethanolic extract of Cordia
      macleodii leaves for possible antioxidant and hepatoprotective potential.
      Antioxidant activity of the extracts was evaluated by four established, in vitro
      methods viz. 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging method,
      nitric oxide (NO) radical scavenging method, iron chelation method and reducing
      power method. The extract demonstrated a significant dose dependent antioxidant
      activity comparable with ascorbic acid. The extract was also evaluated for
      hepatoprotective activity by carbon tetrachloride (CCl4) induced liver damage
      model in rats. CCl4 produced a significant increase in levels of serum glutamate
      pyruvate transaminase (GPT), serum glutamate oxaloacetate transaminase (GOT),
      Alkaline Phosphatase (ALP) and total bilirubin. Pretreatment of the rats with
      ethanolic extract of C. macleodii (100, 200 and 400 mg/kg po) inhibited the
      increase in levels of GPT, GOT, ALP and total bilirubin and the inhibition was
      comparable with Silymarin (100 mg/kg po). The present study revealed that C.
      macleodii leaves have significant radical scavenging and hepatoprotective
      activities. 

PMID- 23960715
TI  - Determination of diosmin in pharmaceutical formulations using Fourier transform
      infrared spectrophotometry.
AB  - A Fourier transform infrared (FT-IR) spectrometric method was developed for the
      rapid, direct measurement of diosmin in different pharmaceutical drugs.
      Conventional KBr-spectra were compared for best determination of active substance
      in commercial preparations. The Beer-Lambert law and two chemometric approaches,
      partial least squares (PLS) and principal component regression (PCR+) methods,
      were tried in data processing. 

PMID- 23960716
TI  - Biological importance of marine algae.
AB  - Marine organisms are potentially prolific sources of highly bioactive secondary
      metabolites that might represent useful leads in the development of new
      pharmaceutical agents. Algae can be classified into two main groups; first one is
      the microalgae, which includes blue green algae, dinoflagellates, bacillariophyta
      (diatoms)... etc., and second one is macroalgae (seaweeds) which includes green,
      brown and red algae. The microalgae phyla have been recognized to provide
      chemical and pharmacological novelty and diversity. Moreover, microalgae are
      considered as the actual producers of some highly bioactive compounds found in
      marine resources. Red algae are considered as the most important source of many
      biologically active metabolites in comparison to other algal classes. Seaweeds
      are used for great number of application by man. The principal use of seaweeds as
      a source of human food and as a source of gums (phycocollides). Phycocolloides
      like agar agar, alginic acid and carrageenan are primarily constituents of brown
      and red algal cell walls and are widely used in industry. 

PMID- 23960717
TI  - Protective effect of Jasonia montana against ethinylestradiol-induced cholestasis
      in rats.
AB  - Estrogens, and particularly glucuronides such as ethinylestradiol (EE), have been
      shown to cause cholestasis in animal studies, by reducing bile acid uptake by
      hepatocytes. The aim of the present article is to investigate anticholestatic
      activity of the ethanolic extract of the aerial parts of Jasonia montana against
      liver cholestasis induced by EE in adult female rats in an attempt to understand
      its mechanism of action, which may pave the way for possible therapeutic
      applications. Subcutaneous administration of 100 MUg/kg b.w. ethinylestradiol to
      rats induced hepatocellular cholestasis with a significant decrease in serum
      cholesterol, bile acids and bilirubin levels as well as in hepatic superoxide
      dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR)
      activities and hepatic total, protein-bound and non-protein sulfhydryl groups.
      Also, treatment with EE produced significant increase in serum Pi-glutathione-s
      transferase (Pi-GST), gamma glutamyl transpeptidase (gamma-GT) and alpha
      glutathione-s-transferase (alpha-GST) activities as well as serum nitric oxide
      (NO) and tumor necrosis factor alpha (TNF-alpha) level and hepatic
      malondialdehyde (MDA) level as compare to control group. Oral administration of
      the aerial parts of ethanolic extract at a concentration of 150 mg/kg b.w. daily
      to rats treated with EE for 15 days showed a significant protection against
      induced decrease in serum cholesterol, bile acids and bilirubin levels. The
      treatment also resulted in a significant increase in hepatic SOD, GPx and GR
      activities as well as hepatic total, protein-bound and non-protein sulfhydryl
      groups. In addition, the extract could inhibit serum Pi-GST, gamma-GT and alpha
      GST activities as well as reduce serum TNF-alpha, NO and hepatic MDA as compare
      to ethinylestradiol treated rats. High content of flavonoids and phenolic
      compounds was found in ethanolic extract, which may be responsible for free
      radical activity. The results clearly suggest that the aerial parts of J. montana
      extract may effectively normalize the impaired antioxidant status in
      ethinylestradiol (EE)-cholestatic model. Thus the extract may have a therapeutic
      value in drug-induced biliary cholestasis as well as in hormonal therapy. 

PMID- 23960718
TI  - The prevalence of HCV antibodies in skin disease patients in Saudi Arabia.
AB  - BACKGROUND/AIM: Hepatitis C virus (HCV) infection is a worldwide health issue
      with about 3% of the world's population having HCV. In Saudi Arabia, prevalence
      ranges from 1.0% to 5.87%. Cutaneous diseases can indicate the presence of HCV
      infection. OBJECTIVES: The research project aims to identify prospectively the
      prevalence of HCV infection in 200 patients with various types of skin disorders
      and 50 healthy blood donors, and to quantify this association through clinical
      and laboratory investigations. METHODS: Two hundred patients with cutaneous
      manifestations who presented at the Dermatology outpatient clinics of King Khalid
      University Hospital (KKUH) and King Abdulaziz University Hospital (KAUH), Riyadh,
      and 50 healthy blood donors were prospectively studied. Patients were examined by
      a team of dermatologists and clinical data were collected through a standard
      questionnaire. Ten milliliters of venous blood were collected from fully
      consented, 8-10 h fasting patients and serum was analyzed for AST, ALT, double
      infection with HBsAg, anti-HCV antibodies, and screened for HCV-RNA-PCR. RESULTS:
      Patients from the study (n = 200) consisted of 25 (12.5%) males and 175 (87.5%)
      females, with a mean age of 42.9 +/- 15.06 years. Clinical examinations revealed
      that (35%) had urticaria, followed by pruritus (28%), lichen planus (25.5%),
      prurigo (10%), and palpable purpura (1.5%). The main serum levels of ALT and AST
      were within the normal reference ranges. Twenty-four patients (12%) tested
      positive for anti-HCV antibodies, with 15 (62.5%) being positive for the presence
      of HCV-RNA by PCR and 9 (37.5%) resulting negative for the viral RNA. Of the 24
      anti-HCV positive patients, pruritus 12 (50%), urticaria 5 (20.8%), lichen planus
      5(20.8%), and palpable purpura 2(8.3%). Five (2.5%) patients were positive for
      HBsAg, with 3 (60%) having pruritus and 2 (40%) presenting with urticaria. Of the
      50 healthy blood donors, only one (2%) tested positive for the presence of anti
      HCV antibodies, and all the donors tested negative for HBsAg. CONCLUSION: Results
      clearly indicate the prevalence of anti-HCV antibodies in 24 out of 200 patients
      (12%) with skin manifestations seen at the dermatology outpatient clinics and
      documented with HCV-RNA-PCR positivity of 15/24 (62.5%). A p-value of <0.05 was
      considered significant, therefore, it is suggested that patients presenting with
      urticaria, pruritus and LP be investigated to exclude the possibility of HCV
      infection.

PMID- 23960719
TI  - Leptin levels in relation to marital status and neuroendocrine function in Iraqi
      females with polycystic ovary syndrome.
AB  - The present study was designed to evaluate the relationship between serum leptin
      levels and the hormones related to fertility in Iraqi females with polycystic
      ovary syndrome (PCOS) and marital status. This study was conducted during the
      period from July to December 2007. Twenty-four women (12 married and 12
      unmarried) with PCOS and not maintained on any type of therapy were included in
      the study. Twelve healthy and normal ovulatory women with an age range matched
      with that of PCOS women were included. After an overnight fasting, blood samples
      were drawn from all women at random days. While in those with regular menstrual
      cycles, blood samples were obtained during the follicular phase of the cycle,
      except for samples utilized for the assay of progesterone that performed in the
      day 21 of the cycle (luteal phase). After preparation of serum, the levels of
      leptin, luteinizing hormone (LH), follicle-stimulation hormone (FSH),
      progesterone, testosterone and prolactin were analyzed. Both groups of PCOS
      patients showed significantly lower levels of serum leptin, while prolactin, LH
      and FSH and testosterone were significantly elevated compared to controls. No
      significant differences were reported among PCOS patients with different marital
      status. In conclusion, impaired plasma leptin levels in PCOS women were
      associated with impaired endocrinological parameters related to fertility. 

PMID- 23960720
TI  - Determination of mirtazapine in spiked human plasma and tablets by first
      derivative spectrofluorimetric method.
AB  - A sensitive first derivative spectrofluorimetric method ((1)D-spectrofluorimetry)
      was developed for the determination of mirtazapine. Calibration graph for
      mirtazapine determination was established using the first derivative amplitudes
      of the mirtazapine emission spectrum (lambda ex = 314 nm) in 0.1 M sulphuric acid
      measured at 375-435 nm from peak to peak, as the analytical signals. Moreover,
      the ratio of (1)D-spectrophotometric peak amplitudes at these wavelengths was
      calculated and used for the detection of the presence of interferences. Linearity
      range was found to be between 1 and 40 ng ml(-1) with correlation coefficient (r)
      = 0.9999. The limit of quantitation (LOQ) was 1.0 ng ml(-1) and the limit of
      detection (LOD) was 0.2 ng ml(-1). The proposed method was validated according to
      ICH; and it has been applied for the drug determination in human plasma without
      prior extraction and in tablets. The proposed method's accuracy, reproducibility,
      selectivity and simplicity suggest its application in quality control analysis of
      the drug. 

PMID- 23960721
TI  - Organosulfur compounds and possible mechanism of garlic in cancer.
AB  - Garlic (Allium sativum), a member of the family Liliaceae, contains an abundance
      of chemical compounds that have been shown to possess beneficial effects to
      protect against several diseases, including cancer. Evidence supports the
      protective effects of garlic in stomach, colorectal, breast cancer in humans. The
      protective effects appear to be related to the presence of organosulfur
      compounds, predominantly allyl derivatives, which also have been shown to inhibit
      carcinogenesis in forestomach, esophagus, colon, mammary gland and lung of
      experimental animals. The exact mechanisms of the cancer-preventive effects are
      not clear, although several hypotheses have been proposed. Organosulfur compounds
      modulate the activity of several metabolizing enzymes that activate (cytochrome
      P450s) or detoxify (glutathione S-transferases) carcinogens and inhibit the
      formation of DNA adducts in several target tissues. Antiproliferative activity
      has been described in several tumor cell lines, which is possibly mediated by
      induction of apoptosis and alterations of the cell cycle. Organosulfur compounds
      in garlic are thus possible cancer-preventive agents. Clinical trials will be
      required to define the effective dose that has no toxicity in humans. 

PMID- 23960723
TI  - Effect of tobacco smoking on tissue protein citrullination and disease
      progression in patients with rheumatoid arthritis.
AB  - The aim of the present work was to study the effect of tobacco smoking on disease
      progression in rheumatoid arthritis patients and its relation to anti-cyclical
      citrullinated peptide (anti-CCP) antibodies. The study included 54 patients; 20
      non-smokers, 9 ex-smokers, 14 mild to moderate smokers and 11 heavy smokers.
      Fifteen normal volunteers were also studied as controls. Disease stage was
      clinically and radiologically determined, rheumatoid factor (RF) and anti-CCP
      antibodies were measured in serum. Higher percentage of severe disease (stage
      III) was seen in heavy smoker patients than mild to moderate smokers (54.6%
      versus 35.7%) and in moderate smokers than ex-smokers (35.7% versus 33.6%).
      Lowest percentage of severe disease was seen in non-smokers (15%). RF and anti
      CCP were significantly higher in smoker than non-smoker and in heavy than mild to
      moderate smoker patients (p < 0.01, p < 0.05 and p < 0.01, p < 0.001,
      respectively). In smoker patients, both RF and anti-CCP antibodies correlated
      significantly and positively with smoking index (r = 0.581, p < 0.001; r = 0.661,
      p < 0.001). Also, smoking index and anti-CCP correlated significantly and
      positively with disease stage (r = 0.424, p < 0.05; r = 0.523, p < 0.01). It
      appears from our results that, tobacco smoking mostly play a role in progression
      of rheumatoid arthritis through tissue protein citrullination. So all rheumatoid
      arthritis patients must quit completely to achieve a good control. 

PMID- 23960722
TI  - Separation of biological proteins by liquid chromatography.
AB  - After the success of human genome project, proteome is a new emerging field of
      biochemistry as it provides the knowledge of enzymes (proteins) interactions with
      different body organs and medicines administrated into human body. Therefore, the
      study of proteomics is very important for the development of new and effective
      drugs to control many lethal diseases. In proteomics study, analyses of proteome
      is essential and significant from the pathological point of views, i.e., in
      several serious diseases such as cancer, Alzheimer's disease and aging, heart
      diseases and also for plant biology. The separation and identification of
      proteomics is a challenging job due to their complex structures and closely
      related physico-chemical behaviors. However, the recent advances in liquid
      chromatography make this job easy. Various kinds of liquid chromatography, along
      with different detectors and optimization strategies, have been discussed in this
      article. Besides, attempts have been made to include chirality concept in
      proteomics for understanding mechanism and medication of various disease
      controlled by different body proteins. 

PMID- 23960724
TI  - Utilization of date syrup as a tablet binder, comparative study.
AB  - The aim of this study was to investigate the possibility of using dates syrup as
      a tablet binder. Dates syrup (40%, 50%, 60% w/w dates syrup:water) was utilized
      for the granulation of sodium bicarbonate and calcium carbonate as examples for
      water-soluble and water-insoluble materials; correspondingly. Those two materials
      represent examples of bulky drugs as well. Starch paste (10% w/w starch in water)
      and sucrose syrup (50% w/w sucrose in water), the well-known tablet binders, were
      used in the granulation of the same materials for the sake of comparison. The
      granulations were evaluated with regard to particle size and particle size
      distribution, granule strength, bulk density, flowability, moisture content and
      compression behavior. In addition, tablets prepared and evaluated from these
      granules. Taste and flavor of the prepared tablet have been tested by seven
      healthy volunteers. Within the scope of this work, dates syrup showed excellent
      properties as a tablet binder in comparison to starch paste or sucrose syrup for
      the granulation of both water-soluble and water-insoluble materials. Also, better
      flavoring and masking taste have been noticed from an evaluation by human
      volunteers demonstrating the usefulness of the date syrup as sweetener and
      flavoring the tablets in addition to its use as binder. 

PMID- 23960725
TI  - Influence of intestinal efflux pumps on the absorption and transport of
      furosemide.
AB  - PURPOSE: Furosemide is a commonly used diuretic which is used in the treatment of
      edema, congestive heart failure, hypertension and renal failure. Its absorption
      exhibits inter- and intra-subject variability that can be attributed to many
      factors including the intestinal efflux pumps such as the P-glycoprotein (P-gp).
      This study was done due to the great disagreement between what is published in
      the literature regarding the influence of P-gp on furosemide and at the same time
      due to the importance of this drug in the treatment of different conditions as
      described above. In addition, an investigation of the effect of two of the
      commonly used pharmaceutical excipients (hydroxypropyl beta-cyclodextrin
      [HPbetaCD] and Tween 80) and also a P-gp inhibitor (verapamil hydrochloride) on
      the intestinal absorption of this drug were also done. METHODS: The study
      utilized the everted intestinal sacs technique to investigate both the effect of
      the efflux transporter (P-gp) on furosemide absorption and also the effect of the
      chosen excipients. RESULTS: The absorption of furosemide was significantly
      influenced by the P-gp as confirmed by the everted vis the non-everted sacs
      together with the verapamil study in which the transport of furosemide was
      inhibited by verapamil. In addition, Tween 80 was also shown to inhibit the P-gp
      pump whereas the HPbetaCD did not significantly influence the efflux of
      furosemide in this study. CONCLUSIONS: P-glycoprotein and some of the used
      excipients in the formulation play a very important role in the transport of
      furosemide and other drugs. Thus excipients that affect the activity of P-gp
      should be avoided when formulating drugs that are substrate for the P-gp or other
      efflux pumps.

PMID- 23960726
TI  - Normal-phase LC method for simultaneous analysis of pseudophedrine hydrochloride,
      dextromethorphan hydrobromide, chlorpheniramine maleate, and paracetamol in
      tablet formulations.
AB  - A simple, precise, and accurate method is developed and validated for the
      analysis of pseudophedrine hydrochloride, dextromethorphan hydrobromide,
      chlorpheniramine maleate, and paracetamol in tablet formulations. The method has
      shown adequate separation of the four ingredients from each other. Separation was
      achieved on a silica column (5 MUm, 125 * 4.6 mm inner diameter) using a mobile
      phase consisting of methanol/ammonium dihydrogen phosphate buffer (90:10, v/v) at
      a flow rate of 1.0 ml/min and UV detection at 220 nm. This new method is
      validated in accordance with USP requirements for new methods for assay
      determination, which include accuracy, precision, selectivity, linearity and
      range, robustness and ruggedness. The current method demonstrates good linearity
      over the range of 0.15-0.45 mg/ml of pseudophedrine hydrochloride with r (2) of
      0.996, and in the range of 0.075-0.225 mg/ml of dextromethorphan hydrobromide
      with r (2) of 0.992, and in the range of 0.01-0.03 mg/ml of chlorpheniramine
      maleate with r (2) of 0.994, and in the range of 0.25-0.75 mg/ml of paracetamol
      with r (2) of 0.991. The average recovery of the method is 99.7%, 98.6%, 98.1%,
      and 99.2% for pseudophedrine hydrochloride, dextromethorphan hydrobromide,
      chlorpheniramine maleate, and paracetamol, respectively. The degree of
      reproducibility of the results obtained as a result of small deliberate
      variations in the method parameters and by changing analytical operator has
      proven that the method is robust and rugged. 

PMID- 23960727
TI  - Cataract associated with high-dose hematopoietic colony stimulating factor, case
      report and literature review.
AB  - Granulocyte-colony stimulating factor (G-CSF) is a lineage-restricted
      hematopoietic growth factor. It induces proliferation and maturation of
      neutrophilic precursors and progenitors and activates neutrophil functions. It is
      used to ameliorate or prevent profound neutropenia and its consequences. G-CSF
      therapy in neutropenic disorders increases neutrophil count and improves
      infectious complications. However, it is not without side effects. Here, we
      discuss the case of a 2 years old patient with Kostmann's disease who developed
      cataracts following high-dose G-CSF therapy. We also review the relevant
      literature on G-CSF-related complications. 

PMID- 23960728
TI  - Role of carnitine in cancer chemotherapy-induced multiple organ toxicity.
AB  - In the last few years, cancer chemotherapy has been successfully employed in the
      treatment of different types of human tumours. Unfortunately, the optimal
      clinical usefulness of this important treatment modality is usually limited
      secondary to the development of life-threatening multiple organ toxicity. Cancer
      chemotherapy may cause these toxic effects by mechanisms not involved in their
      anticancer activity that can severely affect the life of patients and represent a
      direct cause of death. Several experimental and clinical studies have
      demonstrated that some important anticancer drugs interfere with the absorption,
      synthesis, and excretion of carnitine in non-tumour tissues, resulting in a
      secondary carnitine deficiency which is reversed by carnitine treatment without
      affecting anticancer therapeutic efficacy. Prototypes of anticancer drugs that
      alter carnitine system are doxorubicin, cisplatin, carboplatin, oxaliplatin,
      cyclophosphamide and ifosfamide. Furthermore, cachectic cancer patients are
      especially at risk for carnitine deficiency due to decreased oral intake and/or
      increased renal losses. Altered serum and urine carnitine levels have been
      reported in cancer patients with various forms of malignant diseases. Recent
      studies in our laboratory have demonstrated that carnitine deficiency constitute
      a risk factor and should be viewed as a mechanism during development of
      oxazaphosphorines-induced cardiotoxicity in rats. Similarly, inhibition of gene
      expression of heart fatty acid-binding protein and organic cation/carnitine
      transporter in doxorubicin cardiomyopathic rat model has been reported. In view
      of these facts and in view of irreplaceability of these important anticancer
      drugs, this review aimed to highlight the role of carnitine depletion and
      supplementation during development of chemotherapy-induced multiple organ
      toxicity. 

PMID- 23960729
TI  - Evaluation of the role of striatal cannabinoid CB1 receptors on movement activity
      of parkinsonian rats induced by reserpine.
AB  - It has been observed cannabinoid CB1 receptor signalling and the levels of
      endocannabinoid ligands significantly increased in the basal ganglia and
      cerebrospinal fluids of Parkinson's disease (PD) patients. These evidences
      suggest that the blocking of cannabinoid CB1 receptors might be beneficial to
      improve movement disorders as a sign of PD. In this study, a dose-response study
      of the effects of intrastriatal injection of a cannabinoid CB1 receptor
      antagonist, AM251 and agonist, ACPA, on movement activity was performed by
      measuring the catalepsy of reserpinized and non-PD (normal) rats with bar test.
      Also the effect of co-administration the most effective dose of AM251 and several
      doses of ACPA were assessed. AM251 decreases the reserpine induced catalepsy in
      dose dependent manner and ACPA causes catalepsy in normal rats in dose dependant
      manner as well. AM251 significantly reverse the cataleptic effect in all three
      groups (1, 10, 100 ng/rat) that received ACPA. These results support this theory
      that cannabinoid CB1 receptor antagonists might be useful to alleviate movement
      disorder in PD. Also continuance of ACPA induced catalepsy in rats after AM251
      injection can indicate that other neurotransmitters or receptors interfere in
      ACPA induced catalepsy. Based on the present finding there is an incomplete
      overlapping between cannabinoid CB1 receptor agonist and antagonist effects. 

PMID- 23960730
TI  - Effect of formulation design and freeze-drying on properties of fluconazole
      multilamellar liposomes.
AB  - Fluconazole-entrapped multilamellar liposomes were prepared using the thin-film
      hydration method. The effects of cholesterol molar ratio, charge-inducing agents,
      and alpha-tocopherol acetate on encapsulation efficiency values and in vitro drug
      release of multilamellar liposomes were studied. Freeze-dried liposomal products
      were prepared with or without cryoprotectants. Results showed that incorporation
      of stearylamine resulted in an increased entrapment of fluconazole, whereas
      incorporation of dicetyl phosphate decreased the drug entrapment efficiency. The
      incorporation of alpha-tocopherol acetate into fluconazole multilamellar
      liposomes resulted in the increase of entrapment efficiency of fluconazole
      liposomes. In vitro release studies revealed that incorporation of cholesterol
      into multilamellar liposomal formulations decreased drug permeability from
      formulations. Positively charged fluconazole multilamellar liposomes gave rise to
      a slow release rate compared to neutral liposomes whereas negatively charged
      fluconazole liposomes showed a rapid release rate. Physical stability studies
      showed that lyophilized cake of liposomes without cryoprotectants was compact and
      difficult to reconstitute compared to fluffy easily reconstituted cakes upon
      using cryoprotectants. Fluconazole retained in freeze-dried liposomes without
      cryoprotectants was 63.452% compared to 91.877% using three grams of trehalose as
      a cryoprotectant per gram lipid in positively charged multilamellar liposomes.
      Physical stability studies showed superior potentials of the lyophilized product
      after reconstitution in comparison with those of a solution product. 

PMID- 23960731
TI  - Measuring the rate of therapeutic adherence among outpatients with T2DM in Egypt.
AB  - BACKGROUND AND OBJECTIVE: The promotion of therapeutic adherence is considered as
      an integral component of pharmaceutical care practice and patient healthcare. It
      has been shown that despite effective methods of treatment, 50% of diabetic
      patients fail to achieve satisfactory glycemic control, which leads to
      accelerated development of complications and increased mortality. Clinical
      experience indicates that no improvement of metabolic control is possible without
      patients' adherence to medications. This study sought to examine the rate of
      medication adherence and different factors affecting it among Type 2 diabetic
      patients in Egypt. METHODS: A total of 226 Type 2 diabetic patients who fulfilled
      the inclusion criteria were recruited in the current study. Adherence to the
      treatment was evaluated during patients' hospitalization in the Outpatient
      Clinics of Internal Medicine Department at University of Mansoura, Egypt. The
      medication adherence has been assessed during a personal interview with each
      patient using a multiple-choice graded questionnaire. RESULTS: In the study
      population, the adherence rates to medication, dietary/exercise and appointment
      were observed to be suboptimal. The most important social factors that were
      significantly affecting adherence rate to the prescribed oral hypoglycemic
      agent(s) included marital status (P < 0.01), family support (P < 0.01), and socio
      economical level (P < 0.01). Other patient factors that were significantly
      affecting therapeutic adherence were patient knowledge about the disease (P <
      0.01), patients' beliefs and motivation about prescribed drugs (P < 0.01), and
      regularity of patients' self monitoring of blood glucose level (P < 0.01). Among
      drug factors which found to affect significantly the rate of medication adherence
      are the number of drugs taken (P < 0.05), complexity of drug regimen (P < 0.01),
      and the presence of drug side effects (P < 0.01). Economical factor played an
      equally important role. Direct and indirect care costs in relation to patients'
      income were significantly affecting the rate of adherence to medication (P <
      0.01). CONCLUSIONS: An improvement with the adherence to oral hypoglycemic
      agent(s) may be achieved through continuing patient education about diabetes,
      improvement of patients' economical levels as well as a reduction in the cost of
      medication. Pharmaceutical companies have to be involved and pharmacists have to
      be payed for helping chronically ill patients to take their medicines correctly
      for improving clinical outcomes.

PMID- 23960732
TI  - Development of a capillary electrophoresis method for the determination of
      orphenadrine citrate in tablets in the presence of paracetamol.
AB  - A validated method using capillary electrophoresis was developed, for the
      determination of orphenadrine citrate in its tablet formulations, in the presence
      of paracetamol. The method employs a running buffer of 30 mM pentane sulfonate
      sodium, dissolved in 20 mM MOPS buffer pH 7.7. Samples were injected using
      hydrodynamic sample injection mode (25 mbar, for 25 s), using positive polarity
      of 25 kV, at a constant temperature of 30  degrees C. Samples of orphenadrine
      citrate alone or in mixture solutions with paracetamol were exposed to various
      degradation conditions, and were electrophoresed using the recommended condition.
      The method was found to be specific, linear (r (2) = 0.994), precise, accurate,
      and robust, with an LOQ of 0.02 mg/mL. The proposed method was successfully
      applied for measurement of the percentage per label of orphenadrine citrate in
      commercially available tablets. 

PMID- 23960733
TI  - Efficacy of combined topiramate/thioctic acid therapy in migraine prophylaxis.
AB  - Migraine cannot be cured and the aim, shared with the patient, is to minimise the
      impact of the illness on the patient's life and lifestyle. The aim of prophylaxis
      is to reduce the number of migraine attacks. Prophylaxis should be considered
      when appropriately used acute management gives inadequate control of symptoms.
      The efficacy and safety of topiramate 50 mg/d and thioctic acid (alpha-lipoic
      acid) 300 mg/d either as monotherapy or in combination were investigated as
      migraine prophylactic agents. Forty secondary school migraineur girls were
      enrolled in the study. The study was conducted in two phases, a prospective
      baseline phase and 1-month treatment phase. Combined topiramate/thioctic acid
      therapy was more effective than either topiramate or thioctic acid monotherapy as
      a migraine-preventive treatment. Combined topiramate/thioctic acid therapy
      decreased the mean monthly migraine frequency from 5.86 +/- 1.2 to 2.6 +/- 0.98
      (p ? 0.05), topiramate (50 mg/d) from 5.71 +/- 1.4 to 4.75 +/- 1.5 and thioctic
      acid (300 mg/d) from 5.68 +/- 1.6 to 5.22 +/- 1.8. Reduction in mean monthly
      migraine days was also significantly greater in the group receiving combined
      topiramate/thioctic acid (from 12.32 +/- 1.85 to 5.74 +/- 1.1) compared to those
      receiving either topiramate 50 mg/d (from 12.7 +/- 1.34 to 11.85 +/- 1.35) or
      thioctic acid 300 mg/d (from 12.5 +/- 1.72 to 11.65 +/- 1.44). The responder rate
      (% of patients showing ?50% reduction in monthly migraine frequency) was 85% in
      patients receiving combined topiramate/thioctic acid therapy compared to 30% and
      20% in patients receiving either topiramate or thioctic acid, respectively. The
      incidence of adverse events was higher in patients receiving topiramate (50 mg/d)
      monotherapy. The most common adverse events were nausea, fatigue, paraesthesia
      and taste perversion. We conclude that combined topiramate/thioctic acid therapy
      is more effective and better tolerated than topiramate monotherapy. The
      combination has lower monthly medication costs compared to the traditionally used
      topiramate 100 mg monotherapy. 

PMID- 23960734
TI  - Comparative clinical evaluation of ketotifen and montelukast sodium in asthmatic
      Iraqi patients.
AB  - Asthma is a common and chronic inflammatory condition of the airways whose cause
      is not completely understood. Although many classes of drugs are used for
      management of asthma, the response is variable due to multifactor reasons. This
      study was designed to evaluate the outcome of using ketotifen or montelukast
      sodium in Iraqi asthmatic patients. Single blinded randomized clinical trial was
      utilized, in which 100 asthmatic patients were recruited from Al-Karama hospital
      and randomized into two groups; 1st group (50 patients, treated with ketotifen
      for 4 weeks) and 2nd group (50 patients treated with montelukast sodium for 4
      weeks). Asthma symptom score and wheezing were recorded at the beginning (first
      visit) and at the end of the study (after one month). Pulmonary function tests
      (PFTs) were performed by spirometry, and the patients' use of asthma drugs and
      their symptoms were evaluated at each visit. The result showed that asthma
      symptom, chest wheezing, and PFT values were significantly improved in the two
      groups at the end of the study compared to first visit (p < 0.05). All symptoms
      were significantly lower and PFT values were higher in the 2nd group compared to
      1st group (p < 0.05). In conclusion, both ketotifen and montelukast sodium showed
      significant changes in asthma symptoms and PFT after one month of treatment, but
      the changes were more significant with montelukast group (2nd group) compared
      with ketotifen group (1st group) and this indicate that montelukast was more
      effective than ketotifen in treatment of asthmatic patients. 

PMID- 23960735
TI  - Attitude and perception of patients and health care practitioners toward oral
      sustained release dosage forms in Palestine.
AB  - AIM: To evaluate the knowledge of health professionals in Palestine regarding the
      advantages of sustained release dosage forms (SRDFs) over conventional therapy.
      METHODS: Data were gathered from a questionnaire that was handed out to community
      pharmacists, physicians and patients. Pharmaceutical industry decision makers
      were enrolled in this study. Data were analyzed using the SPSS. RESULTS:
      Pharmacists (92.9%) and 89.2% of physicians thought that SRDFs improve patient
      compliance. 81.5% of pharmacists and 77% of physicians were in agreement
      regarding the capacity of SRDFs to maintain therapeutic activity during night. In
      this study, 81.5% of pharmacists and 81% of physicians believed that SRDFs
      provide further advantage with psychiatric patients who forget to take their
      medications. Pharmacists (63.1%) and only 63.5% of physicians believed that SRDFs
      yield a time saving for nurses who use SRDFs in hospital. Only 45.3% of
      physicians and 43.4% of pharmacists thought that SRDFs result in cost saving due
      to better disease management. Pharmacists (95.2%) and 95.9% of physicians agreed
      that SRDFs could be the right choice for faith patient's who must take their
      medication during the month of Ramadan. Pharmacists (66.7%) and 50.7% of
      physicians recognize that SRDFs may be unsafe if they are improperly formulated.
      Bad swallowing was also recognized as inconveniences of SRDFs by 67.9% of
      pharmacists and 57.3% of physicians. Given the above advantages, 75% of patients
      showed economical problems regarding the cost of the single course therapy of
      SRDFs and 100% of interviewed patients were enthusiastic about the advantage of
      SRDFs during Ramadan. CONCLUSION: The advantages of SRDFs are not completely
      understood by Palestinian health professionals. Pharmaceutical industries should
      pay more attention to the development and advertising of SRDFs due to the
      valuable advantages of these dosage forms.

PMID- 23960736
TI  - Tocilizumab: A new anti-rheumatic drug.

PMID- 23960737
TI  - Emerging frontiers of pharmacy education in Saudi Arabia: The metamorphosis in
      the last fifty years.
AB  - The trends in the quality of biomedical education in pharmacy schools have
      witnessed significant changes in the 21st century. With the advent of continuous
      revision and standardization processes of medical curricula throughout the world,
      the focus has been on imparting quality education. This pedagogic paradigm has
      shifted to pharmacy schools. In Saudi Arabia, the concept of "medical and
      pharmacy education" is relatively new as mainstream pharmacy curriculum and
      universities were established only half a century ago. This period has seen major
      changes in the dimension of "pharmacy education" to keep pace with the education
      systems in the United States and Europe. As our knowledge and perceptions about
      pharmaceuticals change with time, this motivates educators to search for better
      teaching alternatives to the ever increasing number of enthusiastic and budding
      pharmacists. Recently, the academic system in Saudi Arabian Pharmacy has adopted
      a more clinically-oriented Pharm. D. curriculum. This paper deals with the major
      changes from the inception of a small pharmacy faculty in 1959, the College of
      Pharmacy at the King Saud University, Riyadh, to the model of progress and a
      prototype of pharmacy colleges in Saudi Arabia. The fifty year chronological
      array can be regarded as an epitome of progress in pharmacy education in Saudi
      Arabia from its traditional curriculum to the modern day Pharm. D. curriculum
      with a high population growth and expanding health care sector, the demand for
      qualified pharmacists is growing and is projected to grow considerably in the
      future. The number of pharmacy graduates is increasing each year by many folds
      and to meet the needs the system lays stress upon a constant revising and
      updating of the current curriculum from a global perspective. 

PMID- 23960738
TI  - Once versus individualized multiple daily dosing of aminoglycosides in critically
      ill patients.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the once
      daily dosing (ODD) program in critically ill Egyptian patients compared to
      individualized multiple daily dosing (MDD) in terms of clinical and
      bacteriological efficacy. In addition, the incidence of nephrotoxicity associated
      with both regimens in this specific group of patients was assessed. METHODS:
      Fifty-two patients with suspected or confirmed bacterial infections admitted to
      the Critical Care Medicine Department, Kasr El-Aini-Cairo University Hospitals
      comprised the study population. The amikacin group (30 patients) was sub-divided
      into 14 patients receiving amikacin ODD (1 g i.v.) and 16 patients receiving
      amikacin in MDD (500 mg i.v./dose). The gentamicin group (22 patients) was sub
      divided into 10 patients receiving the drug ODD (240 mg i.v.) and 12 patients
      receiving gentamicin MDD (80 mg i.v./dose). Amikacin or gentamicin serum levels
      were determined by the enzyme multiplied immunoassay technique using Emit 2000.
      MDD regimen was adjusted based on the individual pharmacokinetic parameters using
      the Sawchuk-Zaske method. RESULTS: There was no significant difference between
      the two dosing regimens with regard to clinical and antibacterial efficacy or
      incidence of nephrotoxicity of both gentamicin and amikacin groups. In the ODD
      regimen, duration of treatment had no effect on increasing incidence of
      nephrotoxicity unlike the individualized MDD regimen. No dose adjustments were
      needed in the once daily dosing regimen since trough concentrations have never
      been above toxic level. CONCLUSIONS: The study showed that the ODD regimen is
      preferred in critically ill patients to individualized MDD as shown by comparable
      efficacy, nephrotoxicity and lesser need for therapeutic drug monitoring and
      frequent dose adjustments required in the individualized MDD regimen.

PMID- 23960739
TI  - Anti-inflammatory activity of telmisartan in rat models of experimentally-induced
      chronic inflammation: Comparative study with dexamethasone.
AB  - Recently, significant progress has been made through the application of
      peroxisome proliferator activated receptor-gamma (PPAR-gamma) agonists as anti
      inflammatory drugs that are efficacious, relatively free of side effects, and can
      be used effectively for a long time. The present study was designed to evaluate
      the dose-response relationship of the anti-inflammatory activity of telmisartan
      in rat models of chronic inflammation. The study protocol includes four stages:
      First stage: 48 rats were allocated into eight groups, each containing six rats,
      for the study of the anti-inflammatory activity of different doses of telmisartan
      in rat model of formaldehyde-induced chronic inflammation. Second stage: six rats
      were used to study the anti-inflammatory activity of telmisartan (1.5 mg/kg) in
      combination with dexamethasone (0.5 mg/kg) in the same model. Third stage: 48
      rats were allocated into eight groups, each containing six rats, for the study of
      the anti-inflammatory activity of telmisartan in rat model of cotton pellet
      induced granuloma. Fourth stage: six rats were used to study the anti
      inflammatory activity of telmisartan (1.5 mg/kg) when used as adjuvant with
      dexamethasone (0.5 mg/kg) in the same model. Telmisartan in a dose-dependent
      pattern (0.1, 0.2. 0.4, 0.6, 1.5, 3 mg/kg) significantly suppressed inflammation
      in rat models of formaldehyde-induced chronic inflammation and cotton pellet
      induced granuloma. When combined with dexamethasone, telmisartan (1.5 mg/kg body
      weight) significantly suppressed inflammation in both models, which is
      significantly higher than all of the effects produced by other approaches of
      treatment when telmisartan used alone. In conclusion, telmisartan decreased
      formaldehyde-induced chronic inflammation and cotton-pellet induced granuloma in
      rats in a dose-dependent pattern. Therefore, it may be considered as a potential
      treatment for chronic inflammatory conditions in human. 

PMID- 23960740
TI  - Hypoglycaemic and anti-diabetic activity of stem bark extracts Erythrina indica
      in normal and alloxan-induced diabetic rats.
AB  - The objective of the study is to investigate the alcoholic (AlcE) and aqueous
      (AqsE) extracts of stem bark of Erythrina indica (Papilionaceae) for
      hypoglycaemic effects in normal and diabetic rats. Diabetes was induced in rats
      by a single dose administration of alloxan (120 mg/kg, i.p.) or by injecting
      dexamethasone (10 mg/kg, i.p.) for 10 days. In normal rats, AlcE and AqsE had
      significantly decreased the blood glucose level (BGL) in a dose dependent manner
      after repeated administration for 7 days. In alloxan-induced diabetic rats, both
      the extracts decreased blood sugar levels with significant improvement in glucose
      tolerance and body weight at the end of 1st, 2nd and 3rd week after test extract
      treatment. In case of dexamethasone induced insulin resistant diabetic rats,
      repeated administration of AlcE and AqsE inhibited the increase in blood glucose
      level and improved glucose tolerance induced by dexamethasone as compared to
      dexamethasone induced diabetic rats. These results suggest that both extracts
      possess hypoglycaemic activity in normal as well as in diabetic rats. Among AlcE
      and AqsE, AqsE possesses better hypoglycaemic activity than AlcE in all the
      models. Preliminary phytochemical investigations revealed that alcoholic extracts
      contain carbohydrates, alkaloids, flavonoids, saponins, phytosterols, phenolics
      and tannins. Aqueous extract contains carbohydrates, alkaloids, flavonoids,
      glycosides, phytosterols and triterpenoids. These phytoconstituents may be
      responsible for the hypoglycaemic activity of the plant. 

PMID- 23960741
TI  - Simple and rapid HPLC method for simultaneous determination of atenolol and
      chlorthalidone in spiked human plasma.
AB  - A simple, sensitive and rapid chromatographic method was developed and validated
      for the simultaneous quantification of atenolol and chlorthalidone in human
      plasma using hydrochlorothiazide as internal standard (IS). The method utilized
      proteins precipitation with acetonitril as the only sample preparation involved
      prior to reverse phase-HPLC. The analytes were chromatographed on Shim-pack
      cyanopropyl column with isocratic elution with 10 mM KH2PO4 (pH 6.0) - methanol
      (70:30, v/v) at ambient temperature with flow rate of 1 mL min(-1) and UV
      detection at 225 nm. The chromatographic run time was less than 10 min for the
      mixture. The calibration curves were linear over the range of 0.1-10 MUg mL(-1).
      The method was validated in terms of accuracy, precision, absolute recovery,
      freeze-thaw stability, bench-top stability and re-injection reproducibility. The
      within- and between-day accuracy and precision were found to be within acceptable
      limits <15%. The analytes were stable after three freeze-thaw cycles (deviation
      <15%). The proposed method was specific for the simultaneous determination of
      atenolol and chlorthalidone in human plasma where there was no interference from
      endogenous biological substances. 

PMID- 23960742
TI  - The role of pharmacoeconomics in formulary decision making in different hospitals
      in Riyadh, Saudi Arabia.
AB  - OBJECTIVE: To assess the trend of using pharmacoeconomic information by Pharmacy
      and Therapeutics (P&T) committees when making formulary decisions. DESIGN: A
      cross-sectional study conducted in 2007, using structured survey questionnaires
      which were distributed to members of the P&T committees in 11 different hospitals
      in Riyadh, Saudi Arabia. RESULTS: A total of 100 survey questionnaires were sent
      to head of pharmacy departments of 11 different hospitals in Riyadh, Saudi
      Arabia. Out of these, 48 questionnaires were completed and returned. Of the total
      respondents participated in the study, 64.58% were medical doctors and 16.66%
      were pharmacists and 75% of the respondents said they have applied
      pharmacoeconomic evaluations in their decision making process. More than 80% of
      the respondents perceived that they had a fair knowledge of pharmacoeconomics.
      Approximately 80% of respondents expressed some degree of agreement that
      pharmacoeconomics should be applied as a decision making tool. The majority of
      decision-makers (95%) expressed the interest in attending workshops on
      pharmacoeconomics. CONCLUSION: The study showed that pharmacoeconomics can play
      an important role in the P&T committee formulary decisions. However, more
      education to health care professionals and to hospital administrators should be
      conducted to facilitate the use of such a tool. Also, hospitals should recruit
      health care professionals with pharmacoeconomic expertise to manage limited
      health resources in the best way available.

PMID- 23960743
TI  - Pattern and determinants of poisoning in a teaching hospital in Riyadh, Saudi
      Arabia.
AB  - BACKGROUND: The Drug and Poison Information Center (DPIC) at King Khalid
      University Hospital, Riyadh, Saudi Arabia, was founded in 1983. Since then it has
      responded adequately to queries from medical and non-medical callers from all
      over the Kingdom. Queries ranged from simple material identification to poisoning
      cases. OBJECTIVES: To assess the pattern and circumstances of poisoning in the
      Kingdom of Saudi Arabia through reviewing data from DPIC in King Khalid
      University hospitals. METHODS: This is a retrospective study of referred cases
      and calls received by DPIC. All records and documentation forms during the study
      period were investigated. RESULTS: This study included 1161 cases. There were
      7.9% infants, 52.9% under 5 years old, 7.2% between 6-12 years old and 32.0% more
      than 12 years old. Number of males with toxic exposure was almost equal to that
      of females. More than 92% of cases were toxic exposure through oral route. Causes
      of poisoning include drugs among 76.7% of cases followed by household chemicals
      (6.8%). Suicidal intention was reported among 25.6% of cases. Using multivariate
      regression analysis, significant predictors of suicidal attempts are more than 12
      years old, patients who were exposed to more than one toxin and patient who came
      to the hospital within 1-3 h since poisoning. RECOMMENDATIONS: Establishing and
      operating DPIC centers throughout the kingdom, in addition to implementing of
      legislations to ban over the counter selling of medications and to sell
      potentially dangerous chemicals in childproof containers.

PMID- 23960744
TI  - Phytochemical and biological studies of Adiantum capillus-veneris L.
AB  - Chromatographic fractionation of the alcoholic extract of the dried fronds of
      Adiantum capillus-veneris L. (Adiantaceae) yielded seven compounds: four
      triterpenoidal compounds belonging to adiantane and filicane groups were isolated
      from the hexane fraction and identified as isoadiantone (1); isoadiantol-B (2); 3
      methoxy-4-hydroxyfilicane (3) and 3,4-dihydroxyfilicane (4) and three flavonoids
      were isolated from the ethyl acetate fraction and identified as: quercetin (5),
      quercetin-3-O-glucoside (6) and quercetin-3-O-rutinoside (rutin) (7). The
      identification of the isolated compounds has been established through their
      physical, chemical and spectroscopic methods including IR, (1)H NMR, (13)C NMR,
      HSQC, HMBC, NOESY and MS. Biological studies of the total alcoholic extract,
      hexane fraction and some of the isolated compounds showed an anti-inflammatory
      activity while the hypoglycemic study of the total alcoholic extract showed a
      significant activity. 

PMID- 23960745
TI  - Synthesis, characterization, and antimicrobial evaluation of carbostyril
      derivatives of 1H-pyrazole.
AB  - A new series of 12 derivatives of 4-pyrazolyl-N-arylquinoline-2,5-dione (4a-l)
      were synthesized by one pot base catalyzed cyclocondensation reaction of 1-aryl-5
      chloro-3-methyl-1H-pyrazole-4-carbaldehyde (1a-c), Meldrum's acid (2) and 3
      arylamino-5,5-disubstitutedcyclohex-2-enone (3a-d). All the compounds were
      characterized by elemental analysis, FT-IR, (1)H NMR and (13)C NMR spectral data
      and were screened, against six bacterial pathogens, namely Bacillus subtilis,
      Clostridium tetani, Streptococcus pneumoniae, Salmonella typhi, Vibrio cholerae,
      Escherichia coli and antifungal activity, against two fungal pathogens
      Aspergillus fumigatus and Candida albicans, using broth microdilution MIC
      (minimum inhibitory concentration) method. Some of the compounds were found to be
      equipotent or more potent than commercial drugs, against most of the employed
      strains, as evident from the screening data. 

PMID- 23960746
TI  - Preparation of a novel floating ring capsule-type dosage form for stomach
      specific delivery.
AB  - Study objectives were to develop a unique floating ring capsule dosage form which
      combines gastric soluble and insoluble portions, and to evaluate its suitability
      for stomach specific drug delivery. New floating ring capsules were developed
      using different polymers and were compared for various parameters. The
      formulation with HPMC and sodium CMC has better floating properties. The effects
      of polymers concentration on drug release were studies by in vitro release
      studies. The interaction studies of combined drug with polymers were determined
      using FT-IR spectroscopy. The entrapped air within the gel barrier and lower
      densities of HPMC and sodium CMC resulted in better floating behavior. Steady
      slow gel formations showed prolonged drug release. The in vitro release rates
      were generally found to be faster with low concentration of carbopol showing
      release within 2 h, while formulations containing high amount of HPMC showed
      release in 8 h. In particular, the higher concentration of HPMC formulation shows
      the best drug release performance. A very low change in peak shift was observed
      only with sodium alginate formulations. Further, FT-IR measurements confirmed the
      absence of any chemical interactions. Results indicate that new floating ring
      capsule is a promise dosage form for stomach specific delivery. 

PMID- 23960747
TI  - Evaluation of starches obtained from four Dioscorea species as binding agent in
      chloroquine phosphate tablet formulations.
AB  - Starches obtained from four Dioscorea species namely Dioscorea dumetorum
      (Bitter), Dioscorea oppositifolia (Chinese), Dioscorea alata (Water), and
      Dioscorea rotundata (White) have been evaluated as binding agents in chloroquine
      phosphate tablet formulations in comparison with official corn starch. The
      compressional properties of the formulations were analyzed using density
      measurements and the Heckel and Kawakita equations. The mechanical properties of
      the tablets were assessed using tensile strength, brittle fracture index (BFI),
      and friability tests while the drug release properties of the tablets were
      assessed using disintegration and dissolution times. The results indicate that
      the four starches vary considerably in their physicochemical properties. The
      ranking for the tensile strength and the disintegration and dissolution times for
      the formulations was Chinese > Bitter > Corn > White > Water while the ranking
      was reversed for BFI and friability. The results suggest that Water, White, and
      Corn could be useful when faster disintegration time of tablets is desired while
      Chinese and Bitter could be more useful when bond strength is of concern and in
      minimizing the problems of lamination and capping in tablet formulation. 

PMID- 23960748
TI  - Beneficial effects of clopidogrel on glycemic indices and oxidative stress in
      patients with type 2 diabetes.
AB  - Objective of present study is to evaluate the possible role of clopidogrel in
      improving glycemic indices and oxidative stress in patients with type 2 diabetes.
      This study was performed on 42 uncontrolled type 2 diabetic patients at the
      specialized center for Endocrinology and Diabetes, Al-Rasafa Directorate of
      Health, Baghdad. All of the patients were treated with (glibenclamide 5 mg at
      morning) and randomized into two groups: the first group includes 22 patients
      treated with clopidogrel tablets (75 mg/day) for 2 months; the second group
      includes 20 patients treated with a placebo formula (sodium bicarbonate 200
      mg/day) for the same period. Treatment with clopidogrel produced significant
      improvement (P < 0.05) in fasting serum glucose (FSG), fasting serum insulin
      level, quantitative insulin sensitivity check index (QUICKI); and oxidative
      stress markers: serum malondialdehyde (MDA) and serum reduced glutathione (GSH)
      compared to their baseline levels. There was significant elevation (P < 0.05) in
      both FSG and fasting serum insulin and the MDA level with significant reduction
      (P < 0.05) in QUICKI of placebo group compared to their baseline levels. However,
      clopidogrel produced significant elevation (P < 0.05) in AST and ALT levels but
      placebo formula caused no significant alteration (P > 0.05) in the serum levels
      of these two enzymes. In conclusion the treatment with clopidogrel improved
      glycemic indices and reduced oxidative stress in patients with type 2 diabetes. 

PMID- 23960749
TI  - Analgesic, anti-inflammatory, antipyretic and toxicological evaluation of some
      newer 3-methyl pyrazolone derivatives.
AB  - In this paper, we described the pharmacological and toxicological studies of
      three pyrazolone derivatives namely PYZ1: 4-[4-N dimethylamino benzylidine]-3
      methyl pyrazolin-5(4H)-one, PYZ2: 4-[2-chlorobenzylidine]-3-methylpyrazolin-5(4H)
      one and PYZ3: 4-[benzylidine]-3-methylpyrazolin-5(4H)-one derivatives. Analgesic,
      anti-inflammatory and antipyretic studies of 3-methyl pyrazolone derivatives at
      400 mg/kg, p.o. have shown significant activity as compared to control. Amongst
      three pyrazolone derivatives, PYZ2 was found to be more active. Based on the
      result of pharmacological studies, PYZ2 was selected for toxicological studies.
      Acute toxicity studies revealed that methyl pyrazolone derivatives are non-toxic
      in rats up to 5000 mg/kg, p.o. The subacute toxicity study of PYZ2 showed that
      decrease in Hb content, RBC and WBC count. In biochemical analysis level of blood
      glucose and bilirubin reduced where as AST, ALT and alkaline phosphatase level
      elevated. Histopathological studies revealed that there was mild toxicity on
      liver and kidney at 1000 mg/kg, p.o. 

PMID- 23960750
TI  - Assessment of the pharmaceutical quality of marketed enteric coated pantoprazole
      sodium sesquihydrate products.
AB  - Pantoprazole sodium sesquihydrate (PSS) is a proton pump inhibitor, used in acid
      related disorders, like peptic ulcer and gastroesophageal reflux. Increasing the
      number of pantoprazole containing products in the market, raises questions of its
      efficacy and generic substitution. The pharmaceutical quality of 6 generic PSS
      enteric coated tablets in 2 local markets was assessed relative to the innovator
      product (pantozol(r)). Uniformity of dosage unit, disintegration and in vitro
      drug release were determined using United States pharmacopeia for delayed release
      tablets. The similarity factor (f2) was assessed using the FDA recommended
      approach (f2 similarity factor). The content uniformity of the innovator product
      was 98.39% of the labeled claim with RSD value of 1.08%, while the content of
      generic products ranged from 96.98% to 98.80% with RSD values of 1.24-2.19%. All
      the products showed no disintegration, cracks or swelling in 0.1 N HCl, except
      product 1, which showed complete disintegration after 20 min. However, the
      disintegration of all the products in phosphate buffer met USP requirements.
      Dissolution of tablets in 0.1 N HCl showed no drug release after 2 h except
      product 1 in which one tablet showed a drug release more than 10% at acid stage
      level A1. In addition, three tablets of this product showed dissolution of 45%,
      48% and 69% at acid stage level A2. The similarity factor f2 of the products was
      between 71 and 74 indicating the similarity in dissolution profiles of all the
      products in accordance to FDA requirements, except product 1 in which f2 value
      was 18.67. 

PMID- 23960752
TI  - Galactomannan gum coated mucoadhesive microspheres of glipizide for treatment of
      type 2 diabetes mellitus: In vitro and in vivo evaluation.
AB  - Type 2 diabetes mellitus is a heterogeneous disease of polygenic origin and
      involves both defective insulin secretion and peripheral insulin resistance.
      Studies have shown that post-meal hyperglycemic spikes are associated with
      increased cardiovascular mortality in type 2 diabetes. Over the past decade, a
      major interest in control of postprandial glucose excursion has emerged and a
      plethora of new medications that specifically target postprandial hyperglycemia
      were discovered. Despite the availability of new agents for treatment of type 2
      diabetes mellitus, oral sulfonylureas remain a cornerstone of therapy, because
      they are relatively inexpensive and are well tolerated. However, hypoglycemia is
      a major safety concern with sulfonylureas and it is one major risk factor
      requiring hospitalization. Glipizide is a potent, rapid-acting with short
      duration of action and well tolerated second-generation sulfonylurea effective in
      reducing postprandial glucose levels. However, risk of postprandial hypoglycemia
      and post-meal glucose excursions, if dose missed before meal; are always
      associated with the use of glipizide for treatment of type 2 diabetes mellitus.
      Since, the site of absorption of glipizide is from stomach thus dosage forms that
      are retained in stomach by mucoadhesion; would increase absorption, improve drug
      efficiency and decrease dose requirements. Microsphere carrier systems made by
      using polymer galactomannan having strong mucoadhesive properties and easily
      biodegradable could be an attractive strategy to formulate. The purpose of this
      research work is to formulate galactomannan coated mucoadhesive microspheres of
      glipizide and systematically evaluate its in vitro characteristics and in vivo
      performance for sustained glucose lowering effect and improvement in diabetic
      condition as compared to immediate release of glipizide. 

PMID- 23960753
TI  - Synthesis, characterization and anticancer activity of certain 3-{4-(5-mercapto
      1,3,4-oxadiazole-2-yl)phenylimino}indolin-2-one derivatives.
AB  - A series of 5- or 7-substituted 3-{4-(5-mercapto-1,3,4-oxadiazol-2
      yl)phenylimino}-indolin-2-one derivatives were synthesized by treating 5-(4
      aminophenyl)-1,3,4-oxadiazole-2-thiol with different isatin derivatives. The
      newly synthesized compounds were characterized on the basis of spectral (FT-IR,
      (1)H NMR, MS) analyses. All the synthesized derivatives were screened for
      anticancer activity against HeLa cancer cell lines using MTT assay. All the
      synthetic compounds produced a dose dependant inhibition of growth of the cells.
      The IC50 values of all the synthetic test compounds were found between 10.64 and
      33.62 MUM. The potency (IC50 values) of anticancer activity of compounds VIb-d
      was comparable with that of known anticancer agent, Cisplatin. Among the
      synthesized 2-indolinones, compounds VIb-d with halogen atom (electron
      withdrawing groups) at C5 position showed the most potent activity. These results
      indicate that C5 substituted derivatives may be useful leads for anticancer drug
      development in the future. 

PMID- 23960751
TI  - Nanoparticles: Emerging carriers for drug delivery.
AB  - The core objective of nanoparticles is to control and manipulate
      biomacromolecular constructs and supramolecular assemblies that are critical to
      living cells in order to improve the quality of human health. By definition,
      these constructs and assemblies are nanoscale and include entities such as drugs,
      proteins, DNA/RNA, viruses, cellular lipid bilayers, cellular receptor sites and
      antibody variable regions critical for immunology and are involved in events of
      nanoscale proportions. The emergence of such nanotherapeutics/diagnostics will
      allow a deeper understanding of human longevity and human ills that include
      cancer, cardiovascular disease and genetic disorders. A technology platform that
      provides a wide range of synthetic nanostructures that may be controlled as a
      function of size, shape and surface chemistry and scale to these nanotechnical
      dimensions will be a critical first step in developing appropriate tools and a
      scientific basis for understanding nanoparticles. 

PMID- 23960754
TI  - Development and validation of a stability indicating UPLC method for
      determination of ticlopidine hydrochloride in its tablet formulation.
AB  - The objective of the current study was the development of a simple, precise and
      accurate isocratic reversed-phase stability indicating Ultra Performance Liquid
      Chromatography [UPLC] assay method and validated for determination of ticlopidine
      hydrochloride in solid pharmaceutical dosage forms. Isocratic separation was
      achieved on a Zorbax SB-C18 (50 mm * 4.6 mm, 1.8 MUm) column using mobile phase
      of methanol-0.01 M ammonium acetate buffer, pH 5.0 (80:20, v/v) at a flow rate of
      0.8 ml min(-1), the injection volume was 4.0 MUl and the detection was carried
      out at 235 nm by using photo-diode array detector. The drug was subjected to
      oxidation, hydrolysis, photolysis and heat to apply stress condition. The method
      was validated for specificity, linearity, precision, accuracy, robustness and
      solution stability. The method was linear in the drug concentration range of 62.5
      375 MUg ml(-1) with a correlation coefficient of 0.9999. The precision (relative
      standard deviation - RSD) of six samples was 1.31% for repeatability and the
      intermediate precision [RSD] among six-sample preparation was 0.77%. The accuracy
      (recovery) was between 98.80% and 101.50%. Degradation products produced as a
      result of stress studies did not interfere with detection of ticlopidine
      hydrochloride and the assay can thus be considered stability indicating. 

PMID- 23960755
TI  - Evidence of carrier mediated transport of ascorbic acid through mammalian cornea.
AB  - The purpose of the present study was to evaluate the transport of ascorbic acid,
      a water soluble molecule, through a predominantly lipophilic cornea. Thus in
      vitro permeation of ascorbic acid from aqueous drops through freshly excised
      mammalian cornea was studied. Aqueous isotonic ophthalmic solutions of ascorbic
      acid of different concentrations (0.125% w/v to 2% w/v) (pH 5.4) were made.
      Further 1.0% w/v or 0.5% w/v ascorbic acid solution containing NaCl or dextrose
      as tonicity modifiers or Na(+)K(+)-ATPase inhibitors were also made. Permeation
      characteristics of drug were evaluated by putting 1 ml formulation on freshly
      excised cornea fixed between donor and receptor compartments of an all-glass
      modified Franz diffusion cell and measuring the drug permeated in the receptor by
      spectrophotometry at 265 nm, after 120 min. Statistical analysis was done by one
      way analysis of variance (ANOVA) followed by Dunnett's test or paired t-test.
      Increase in drug concentration in the formulation resulted in an increase in the
      quantity permeated but after a certain level increase in permeation with increase
      in concentration was minimal. Aqueous drops made isotonic with dextrose showed
      decreased permeation through paired cornea compared with aqueous drops made
      isotonic with NaCl from 1% w/v ascorbic acid solution suggesting likely
      involvement of Na(+) co-transporter but there was decreased permeation through
      0.5% w/v ascorbic acid solution made isotonic with NaCl as compared to solution
      made isotonic with dextrose. Further aqueous drops containing Na(+)K(+)-ATPase
      inhibitor {MAG-Mono Ammonium Glycyrrhizinate (25 MUmol)} showed decreased corneal
      permeation from 0.5% w/v ascorbic acid solution but there was not significant
      decrease from 1% ascorbic acid solution since MAG is a competitive inhibitor of
      ascorbic acid. Aqueous drops containing Na(+)K(+)-ATPase inhibitor {MAG (50
      MUmol) or Ouabain (1 mmol)} showed decreased corneal permeation of ascorbic acid
      compared with control from 1% ascorbic acid solution confirming the involvement
      of Na(+) co-transporter. 

PMID- 23960756
TI  - Protective effect of leaves of Raphinus sativus Linn on experimentally induced
      gastric ulcers in rats.
AB  - Raphinus sativus Linn (Cruciferae) commonly known as 'Radish' is a multipurpose
      herb cultivated in different parts of the world for its edible roots and leaves.
      The present study was aimed to evaluate the antiulcer activity of leaf extracts
      of R. sativus Linn on acetic acid induced chronic gastric ulcer and pylorus
      ligation induced gastric ulcer in rats. The acute oral toxicity study revealed
      that all the extracts were safe up to 2000 mg/kg per oral dose; hence one-tenth
      of this dose was selected for evaluation of antiulcer activity. In acetic acid
      induced gastric ulcer models, the ERS, CRS, EARS and AQRS have offered
      significant protection against acetic acid induced ulcers when compared to
      control group. While in pylorus ligation induced ulcer model the ERS, EARS and
      AQRS showed significant protection by decreasing the ulcer index, total acidity
      and free acidity. In conclusion the leaf extracts of R. sativus Linn are found to
      possess antiulcer property in the experimental animal models of gastric ulcers,
      which is consistent with the literature report in the folk medicine. 

PMID- 23960757
TI  - Free radical scavenging activity of silibinin in nitrite-induced hemoglobin
      oxidation and membrane fragility models.
AB  - Free radical formation in heme proteins is recognized as a factor in mediating
      the toxicity of many drugs. Xenobiotics and drug therapy-related toxicity, due to
      oxidative modification of hemoglobin (Hb), has been attributed in part to the
      uncontrolled oxidative reactions. A variety of antioxidant strategies to
      ameliorate potential oxidative damage in vivo have been suggested. The present
      study was designed to evaluate the dose-response relationship of the free radical
      scavenging properties of silibinin dihemisuccinate (SDH) in nitrite-induced Hb
      oxidation in vitro and in vivo. Different concentrations of SDH were added,
      before and after different intervals of inducing Hb oxidation in erythrocytes
      lysate, and formation of methemoglobin (MetHb) was monitored
      spectrophotometrically; the same approach was utilized to evaluate the effect of
      the same doses of SDH on the integrity of erythrocytes after induction of
      hemolysis. Moreover, the most effective dose of SDH was administered in rats
      before challenge with toxic dose of sodium nitrite, and MetHb formation was
      monitored as mentioned before. The results showed that in both in vitro and in
      vivo models, SDH successfully attenuates Hb oxidation after challenge with sodium
      nitrite; this protective effect was not related to the stage of the catalytic
      stage of Hb oxidation, though the effect was more prominent when the compound was
      administered before nitrite. In conclusion, SDH can effectively, in concentration
      dependent pattern, attenuate sodium nitrite-induced Hb oxidation and maintain
      integrity of red blood cells both in vitro and in vivo. 

PMID- 23960758
TI  - A validated HPTLC method for determination of terbutaline sulfate in biological
      samples: Application to pharmacokinetic study.
AB  - Terbutaline sulfate (TBS) was assayed in biological samples by validated HPTLC
      method. Densitometric analysis of TBS was carried out at 366 nm on precoated TLC
      aluminum plates with silica gel 60F254 as a stationary phase and chloroform
      methanol (9.0:1.0, v/v) as a mobile phase. TBS was well resolved at RF 0.34 +/-
      0.02. In all matrices, the calibration curve appeared linear (r (2) ? 0.9943) in
      the tested range of 100-1000 ng spot(-1) with a limit of quantification of 18.35
      ng spot(-1). Drug recovery from biological fluids averaged ?95.92%. In both
      matrices, rapid degradation of drug favored and the T 0.5 of drug ranged from
      9.92 to 12.41 h at 4  degrees C and from 6.31 to 9.13 h at 20  degrees C. Frozen
      at -20  degrees C, this drug was stable for at least 2 months (without losses
      >10%). The maximum plasma concentration (Cpmax) was found to be 5875.03 +/- 114
      ng mL(-1), which is significantly higher than the maximum saliva concentration
      (Csmax, 1501.69 +/- 96 ng mL(-1)). Therefore, the validated method could be used
      to carry out pharmacokinetic studies of the TBS from novel drug delivery systems.

PMID- 23960759
TI  - Inpatient prescribing errors and pharmacist intervention at a teaching hospital
      in Saudi Arabia.
AB  - BACKGROUND: Prescribing errors phenomena are very common within health care
      practice. These errors could result in adverse events and harm to patients.
      Pharmacist has an identified role in minimizing and preventing such errors.
      OBJECTIVES: To detect the incidence of prescribing errors for hospitalized
      patient, to evaluate the clinical impact of pharmacist intervention on the
      detection of these errors, and to propose a program to overcome this problem in a
      teaching hospital. METHODS: For one month period starting November until December
      2009, the inpatient medication charts and orders were identified and rectified by
      ward and practicing pharmacists within inpatient pharmacy services in a teaching
      hospital at King Khalid University Hospital (KKUH) at King Saud University,
      Riyadh, Kingdom of Saudi Arabia on routine daily activities. Data were collected
      and evaluated. The causes of this problem were identified. RESULTS: Approximately
      113 (7.1%) prescribing errors were detected during the study period out of 1580
      medication orders. Wrong strength and wrong administration frequency of the
      prescribed drug were the most errors encountered in the study, which were 35%,
      and 23%, respectively. Other errors such as wrong patient, wrong drug, and wrong
      dose were also encountered. Lack of knowledge of prescribing skill was the main
      cause of such errors. CONCLUSION: Prescribing errors in teaching hospital within
      inpatient pharmacy services were noticed. The applied method in this project
      might be implemented as part of pharmacy quality assurance program for ongoing
      detection and monitoring of such errors. Technology in prescribing process will
      support the practitioner to reduce the incidence of these errors. Forcing ongoing
      professional communication and education within the medical team about
      prescribing errors now appear warranted.

PMID- 23960761
TI  - Development and characterization of Eudragit based mucoadhesive buccal patches of
      salbutamol sulfate.
AB  - For systemic drug delivery, the buccal region offers an attractive route of drug
      administration. Salbutamol sulfate is a short-acting beta2-adrenergic receptor
      agonist used for the relief of bronchospasm in conditions such as asthma and
      chronic obstructive pulmonary disease. It's oral bioavailability is ~40% due to
      extensive first pass metabolism. Salbutamol sulfate patches were prepared using
      Eudragit L-100, HPMC, PVA and Carbopol 934 in various proportions and
      combinations using PEG-400/PG as plasticizers. Patches were laminated on one side
      with a water impermeable backing layer for unidirectional drug release. The
      thickness of medicated patches were ranged between 0.23 +/- 0.008 and 0.59 +/-
      0.007 mm and mass varied between 65.23 +/- 3.3 and 117.92 +/- 4.2 mg. Patches
      showed an increase in mass and swelling index with PEG-400 when compared with PG.
      The surface-pH of patches ranged between 6 and 7. Formulations E7 (7.5 mL
      Eudragit L-100, 15 mL HPMC K4M, 7.5 mL PVA and 2 mL PEG-400), E12 (7.5 mL
      Eudragit L-100, 7.5 mL PVA, 15 mL Carbopol and 2 mL PEG-400), F7 (7.5 mL Eudragit
      L-100, 15 mL HPMC K4M, 7.5 mL PVA and 2 mL PG), and F12 (7.5 mL Eudragit L-100,
      7.5 mL PVA, 15 mL Carbopol and 2 mL PG) showed high folding endurance. Residence
      time of the tested patches ranged between 101 and 110 min. The maximum in vitro
      release was found to be 99.93% over a period of 120 min for formulation F12. Data
      of in vitro release from patches were fitted to different kinetic models such as
      Higuchi and Korsmeyer-Peppas models to explain the release profile. Formulations
      E7 and F7 were best fitted to the non-Fickian, where as formulations E12 and F12
      showed Fickian/anomalous drug release. Stability studies indicated that there was
      no change in the chemical and physical characteristics during the test period. 

PMID- 23960760
TI  - Vaccine adjuvants - Current status and prospects on controlled release
      adjuvancity.
AB  - The strategy of World Health Organization is to develop efficient and inexpensive
      vaccine against various infectious diseases amongst children's population.
      Vaccination is considered as the most cost effective health intervention known to
      public. Since 90 years various substances have been added in vaccine formulation
      but still alum is considered as the safest adjuvant for human use licensed by
      United States Food and Drug Administration. MF 59 and ASO4 are the adjuvants were
      developed recently and approved for human use. Due to poor adjuvancity,
      conventional vaccines require multiple recall injection at approximately time
      intervals to attain optimal immune response. For past approximately two decades
      the vaccine research has been focused towards the alternation of alum type of
      adjuvant in order to increase the immunogenicity. The development of new
      vaccines, is more efficacious or easier to deliver, or both have become an area
      of research that can certainly benefit from controlled release technology.
      Especially, the conversion of multiple administration vaccine into single
      administration vaccine may represent an improved advancement towards the
      betterment of human health care and welfare. Biodegradable polymer microparticles
      have been evaluated for delivering antigens in native form, sustained release
      keeping in mind the safety aspects. In this article we review the overall concept
      of adjuvants in vaccine technology with special focus towards the prospects of
      controlled release antigens. 

PMID- 23960762
TI  - Effects of Montelukast on free radical production in whole blood and isolated
      human polymorphonuclear neutrophils (PMNs) in asthmatic children.
AB  - Montelukast is a highly selective leukotriene-receptor antagonist (LTRA). It is
      widely used in the treatment of bronchial asthma, primarily as an adjunct to
      corticosteroids. Reactive oxygen species (ROSs) play an important role in the
      pathogenesis of asthma and oxidative stress contributing to the initiation and
      worsening of inflammatory respiratory disorders, such as asthma. Antioxidant
      drugs may have a role in minimizing or preventing damage in asthmatic children.
      The aim of this study was to assess the antioxidant effect of montelukast on the
      production of free radicals in the whole blood and polymorphonuclear neutrophils
      (PMNs) in asthmatic children. A group of 48 (38 males and 10 females), apparently
      healthy asthmatic children were recruited with ages ranging between 6 and 14
      years. In asthmatic children, base line (premedication) and post medication free
      radicals activity in the whole blood and polymorphonuclear neutrophils (PMNs) was
      determined by measuring chemiluminescence (CL) response through chemiluminescence
      luminometer. Free radical productions were significantly decreased in the whole
      blood, when stimulated with Phorbol Myristate Acetate (p < 0.04) and Opsonised
      Zymosan (p < 0.05). The free radicals were also significantly decreased in
      isolated polymorphonuclear neutrophils (PMNs) when stimulated with Opsonised
      Zymosan (p < 0.05) after the post medication treatment of montelukast in
      asthmatic children. Montelukast decreased the reactive oxygen species production,
      both in the whole blood as well as isolated PMNs in asthmatic children. 

PMID- 23960763
TI  - Stability-indicating HPTLC method for simultaneous determination of nateglinide
      and metformin hydrochloride in pharmaceutical dosage form.
AB  - A stability indicating high performance thin layer chromatography (HPTLC) method
      was developed and validated for determination of two anti-diabetic drugs,
      nateglinide and metformin hydrochloride in co-formulations. Study was performed
      on pre-coated silica gel HPTLC plates using chloroform:ethyl acetate:acetic acid
      (4:6:0.1 v/v/v) as the mobile phase. A TLC scanner set at 216 nm was used for
      direct evaluation of the chromatograms in the reflectance/absorbance mode. Method
      was validated according to ICH guidelines. The correlation coefficients of
      calibration curves were found to be 0.996 and 0.995 in the concentration range of
      200-2400 and 500-3000 ng band(-1) for nateglinide and metformin, respectively.
      The method had an accuracy of 99.72% for nateglinide and 100.08% for metformin
      hydrochloride. The method had the potential to determine these drugs
      simultaneously from dosage forms without any interference of the tablets
      excipients. Nateglinide and metformin hydrochloride were also subjected to acid,
      base, oxidation, wet, heat and photo-degradation studies. The degradation
      products obtained were well resolved from the pure drugs with significantly
      different Rf values. As the method could effectively separate the drugs from its
      degradation products, it can be used for stability-indicating analysis. 

PMID- 23960764
TI  - Microwave assisted synthesis of novel pyrazolone derivatives attached to a
      pyrimidine moiety and evaluation of their anti-inflammatory, analgesic and
      antipyretic activities.
AB  - In the present research work, the motto was to develop new chemical entities as
      potential anti-inflammatory, analgesic and antipyretic agents. Various 4-(2-amino
      6-(substituted)pyrimidin-4-yl)-3-methyl-1-(substituted)-1H-pyrazol-5(4H)-one
      derivatives (5a-5j) and their Schiff bases (6a-6j) were synthesized. The newly
      synthesized compounds were characterized by TLC and spectral data. The compounds
      containing pyrazolone and amino pyrimidine as basic moieties (5a-5j), were
      screened for their anti-inflammatory, analgesic and antipyretic activities,
      compounds 5a, 5c-5f, 5h exhibited activities nearly similar to the standard. The
      pharmacological studies reveal that the presence of 4-hydroxy, 4-methoxy, 4-(N,N
      dimethylamino) or 2-hydroxy groups on phenyl ring at C6 of amino pyrimidine
      exhibits anti-inflammatory, analgesic and antipyretic activities nearly similar
      to the standard and substitutions like 4-chloro, 2-nitro, 3-nitro or 4-nitro on
      same phenyl ring lead to a decrease in activities. 

PMID- 23960765
TI  - Designing an extended release waxy matrix tablet containing nicardipine-hydroxy
      propyl beta cyclodextrin complex.
AB  - AIM: The current study aimed to prepare a sustained release tablet for a drug
      which has poor solubility in alkaline medium using complexation with
      cyclodextrin. Nicardipine hydrochloride (NC) a weak basic drug was chosen as a
      model drug for this study. METHOD: Firstly the most suitable binary system NC
      HPbetaCD was selected in order to improve drug solubility in the intestinal media
      and then embedding the complexed drug into a plastic matrix, by fusion method,
      consists of glycerol monostearate (GMS) as an inert waxy substance and
      polyethylene glycol 4000 (PEG4000) as a channeling agent, after that the final
      solid dispersion [(NC:HPbetaCD):GMS:PEG4000] which was prepared at different
      ratios was mixed with other excipients, avicel PH101, lactose, and talc, to get a
      tablet owning dissolution profile complying with the FDA and USP requirements for
      the extended release solid dosage forms. RESULTS: Infrared spectroscopy (IR),
      differential scanning colorimetry (DSC), polarized microscopy and X-ray
      diffractometry proved that the coevaporation technique was effective in preparing
      amorphous cyclodextrin complexes with NC and trapping of NC within the HPbetaCD
      cavity by dissolving both in ethanol and evaporate the solvent using a rotavapor
      at 65  degrees C. Dissolution profile of NC enhanced significantly in pH 6.8 from
      NC:HPbetaCD inclusion complex prepared by the rotavapor (t-test Student p <
      0.05). The release of NC from tablet containing [(NC:HPbetaCD):GMS:PEG4000]
      [(1):0.75:0.5] (w/w/w) solid dispersion (F8) was complying with the FDA
      dissolution requirements for extended release dosage forms, and studying the
      kinetics of the release showed that the diffusional contribution is the major
      factor controlling the drug release from that formula. CONCLUSION: The prepared
      waxy matrix tablet containing NC complexes with CD shows promising results as
      extended release tablets.

PMID- 23960766
TI  - Development of an enhanced formulation for delivering sustained release of
      buprenorphine hydrochloride.
AB  - To control the minimum effective dose, and reduce the number and quantity of
      administered potent drugs are unique features of advanced drug delivery in situ
      forming gel formulation. The efficacy, consistency, and increasing the
      application of existing injection therapies can be enhanced through optimization
      of controlled released systems by using FDA approved biodegradable PLGA (poly-d,l
      lactide-co-glycolide) polymer. The purpose of this study was to develop different
      in situ forming implant (ISFI) formulations of buprenorphine hydrochloride for
      post treatment of drug addicts, acute and chronic pains. The drug releases from
      different ISFIs membranes with and without Tween 80 were compared over a period
      of time. Kinetic equation followed the Korsmeyer-Peppas model, as the plots
      showed high linearity. The influence of this additive on polymer properties was
      investigated using differential scanning calorimetry (DSC), and the membranes
      structure was studied by X-ray diffractometry (XRD) and scanning electron
      microscope (SEM). Data revealed that Tween 80 modified the drug release pattern
      using diffusion mechanism and decreased the glass transition temperature (T g)
      significantly. The degree of crystallinity was decreased after phase inversion
      which helps the dissolution of drug from membrane. The porosity of modified
      membranes was in accordance with release profiles. These findings suggest four
      different in situ forming implant formulations which can release various dose of
      the buprenorphine hydrochloride in a prolonged time. Also this surfactant can be
      an attractive additive for modifying the release rate of drugs from PLGA-based
      membrane drug delivery systems. 

PMID- 23960767
TI  - Accuracy of the medication history at admission to hospital in Saudi Arabia.
AB  - OBJECTIVE: Inaccurate medication history at admission to hospitals leads to
      preventable adverse drug events, which in turn increase mortality, morbidity, and
      health care costs. The objective of this study was to investigate the role of
      pharmacists in identifying discrepancies in medication histories at admission to
      a tertiary referral hospital in Saudi Arabia. METHODS: We performed a prospective
      observational study in a 1200 bed tertiary hospital in Riyadh, Saudi Arabia.
      Patients were included if they were aged 16 years or older, were taking 5 or more
      medications, and were able to communicate or were accompanied by a caregiver who
      could communicate. Over 2 months in 2009, a pharmacist interviewed patients to
      ascertain all medications used prior to hospitalization, then all discrepancies
      were discussed with the admitting physician and unintended discrepancies were
      reported as errors. RESULTS: A pharmacist interviewed 60 patients who were taking
      564 medications total. Of these patients, 65% were male, and their mean age was
      62. Patients were taking an average of 9.4 medications. Twenty-two (37%) patients
      had at least one discrepancy, with the most common being omissions of medications
      (35%) and dosage errors (35%). The mean age for patients with discrepancies was
      64.6 years, and without discrepancies, 60.8 years (P = 0.37). CONCLUSION:
      Inaccurate medication history at admission to a hospital was common in Saudi
      Arabia. This has the potential to cause harm to patients if it remains
      undetected. Pharmacists could potentially play a major role in obtaining this
      medication history at the time of hospital admission.

PMID- 23960768
TI  - Toxic effect of Cadmium found in eyeliner to the eye of a 21 year old Saudi
      woman: A case report.
AB  - PURPOSE: To raise the issue of increased use of traditional medicine while the
      Tertiary care hospitals are available to provide the appropriate care for each
      clinical condition. Eyeliner (Kohl) is an Arabic word denoting a fine powder with
      a texture and appearance similar to mascara. It is usually worn on the lid
      margins or inside the conjunctival sac by Middle and Far Eastern and in East
      Africans populations for different purposes like beauty or religious and as a
      treatment for many eye diseases. SUMMARY: We report a case of a lady who put
      traditional locally prepared eyeliner in her eye that resulted in severe corneal
      edema and faint scaring. On toxicology analysis it was discovered to contain
      toxic levels of Cadmium (Cd) and Lead (Pb). CONCLUSION: Cd is a heavy toxic metal
      like Pb but has never been reported as a component of eyeliners. The most likely
      possible cause of the corneal clinical picture in our case is due to the toxic
      effect of Cd found in the traditional eyeliner (Kohl) used in Saudi Arabia.

PMID- 23960769
TI  - Study on drug related hospital admissions in a tertiary care hospital in South
      India.
AB  - BACKGROUND AND OBJECTIVES: Accidental and intentional poisonings or drug
      overdoses constitute a significant source of aggregate morbidity, mortality, and
      health care expenditure. Studies evaluating drug related hospitalization have
      estimated that approximately 5-10% of all hospital admissions are drug related.
      The present study was carried out to investigate type, nature and incidence of
      drug related admissions in our hospital settings. METHOD: A hospital based
      retrospective study was conducted in 575 cases of drug related admissions. The
      case records of patients admitted in various clinical departments of Amrita
      Institute of Medical Sciences (AIMS) Hospital during last 8 years (January 2002
      December 2009) were collected and analyzed. RESULTS: During the retrospective
      study, the total number of drug related cases reported were 575. Out of these,
      35.5% cases were induced by central nervous system (CNS) drugs, 19.8% were by
      cardiovascular system (CVS) drugs, 12.3% were by NSAIDs, 11.3% were by
      antibiotics and 9.9% were by anticoagulants, 11.3% by other drugs which includes
      hormones, cytotoxic drugs, hypolipidemics, etc. Four hundred and forty cases were
      admitted to emergency department. Common drug related problems resulting in
      hospital visits were due to intentional, accidental and overdose. The incidence
      of drug related hospital admissions was found to be 0.20%. CONCLUSION: The most
      of the accidental and suicidal cases were reported are by CNS drugs. Psychiatric
      patients intentionally taking medicines as suicidal attempt and as a part of
      their illness. As drug related problems are so significant, increased awareness
      and enhanced collaborative efforts among patients, physicians, pharmacists and
      caregivers within community and hospital have the potential to minimize the
      impact of this problem.

PMID- 23960770
TI  - Illustration of anti-rheumatic mechanism of rheumavedic capsule.
AB  - The present study was taken up to illustrate the mechanism of anti-rheumatic
      activity of 'Rheumavedic capsule', a polyherbal formulation of Vedic-bio Labs,
      Bangalore, in adjuvant induced arthritic rats. Anti-inflammatory mechanism is
      illustrated using phlogistic agents induced paw edema in rats. Analgesic
      mechanism is illustrated using Eddy's hot plate and acetic acid (0.6%v/v) induced
      writhing in mice. Histopathology of knee joint was studied. Rheumavedic showed
      inhibition of inflammation mediated through Histamine, 5-Hydroxy tryptamine, and
      Bradykinin. Rheumavedic showed protection in both acetic acid and Eddy's hot
      plate induced pain. Histopathology of knee joint of rat pre-treated with
      rheumavedic showed significant reduction in the mononuclear infiltration, pannus
      formation and adhesion molecules. The anti-rheumatic mechanism of rheumavedic is
      due to; inhibition of inflammatory mediators i.e., Histamine, 5-Hydroxy
      tryptamine and Bradykinin., protection against prostaglandins mediated pain, by
      inhibiting cyclo-oxygenase synthesis and reduction in pannus formation, by
      inhibiting mononuclear infiltration. 

PMID- 23960771
TI  - Migraine management: How do the adult and paediatric migraines differ?
AB  - Migraine is one of the common causes of severe and recurring headache. It may be
      difficult to manage in primary care settings, where it is under diagnosed and
      medically treated. Migraine can occur in children as well as in adults and it is
      three times more common in women than in men. Migraine in children is different
      from adults in various ways. Migraine management depends on the various factors
      like duration and severity of pain, associated symptoms, degree of disability,
      and initial response to treatment. The therapy of children and adolescents with
      migraines includes treatment modalities for acute attacks, prophylactic
      medications when the attacks are frequent, and biobehavioural modes of treatment
      to aid long-term management of the disorder. The long lasting outcome of
      childhood headaches and progression into adult headaches remains largely unknown.
      However, it has been suggested that adult migraine may represent a progressive
      disorder. In children, the progressive nature is uncertain and further
      investigations into longitudinal outcome and phenotypic changes in childhood
      headaches have yet to be recognized. Even though paediatric and adult migraines
      seem to be slightly different from one another, but not enough to categorize
      either as sole. 

PMID- 23960772
TI  - Upgrading wet granulation monitoring from hand squeeze test to mixing torque
      rheometry.
AB  - With over 50 years of research in granulation technology, however more research
      is required to elucidate this widely applicable technology. Wetting phenomena
      could influence redistribution of individual ingredients within a granule
      according their solubility and also could affect the drying processes. Binder
      selection for a particular system is quite often empirical and dependent on the
      skills and experience of the formulator. Hand squeeze test was and still the main
      way for determination of wet granulation end point, but it is subjected to
      individual variation. It depends mainly on operator experience, so it is not
      possible to be validated. Literature reveals a variety of advanced monitoring
      techniques following up different wet massing stages. Torque measurement has been
      proved to be the most reliable control method as its tight relation to mass
      resistance. Many reports showed successful applications of mixing torque
      rheometer (MTR) for monitoring the wet massing procedure and scale up in addition
      to some preformulation applications. MTR as a new approach allows formulators to
      select a liquid addition range where the granule growth behavior is more
      predictable. 

PMID- 23960773
TI  - Mucoadhesive buccal patches based on interpolymer complexes of chitosan-pectin
      for delivery of carvedilol.
AB  - The study was designed to develop bioadhesive patches of carvedilol hydrochloride
      using chitosan (CH) and pectin (PE) interpolymer complexes and to systematically
      evaluate their in vitro and in vivo performances. Mucoadhesive buccal patches of
      carvedilol were prepared using solvent casting method. The physicochemical
      interaction between CH and PE was investigated by FTIR and DSC studies. The
      patches were evaluated for their physical characteristics like mass variation,
      content uniformity, folding endurance, ex vivo mucoadhesion strength, ex vivo
      mucoadhesion time, surface pH, in vitro drug release, in situ release study, and
      in vivo bioavailability study. The swelling index of the patches was found to be
      proportional to the PE concentration. The surface pH of all the formulated
      bioadhesive patches was found to lie between 6.2 and 7.2. The optimized
      bioadhesive patch (C1, CH:PE 20:80) showed bioadhesive strength of 22.10 +/- 0.20
      g, in vitro release of 98.73% and ex vivo mucoadhesion time of 451 min with in a
      period of 8 h. The optimized patch demonstrated good in vitro and in vivo
      results. The buccal delivery of carvedilol in rabbits showed a significant
      improvement in bioavailability of carvedilol from patches when compared to oral
      route. 

PMID- 23960774
TI  - Development and validation of an HPLC-UV method for the quantification of
      carbamazepine in rabbit plasma.
AB  - An isocratic simple rapid assay has been developed and validated for the
      determination of carbamazepine (CBZ) in both solution form and rabbit plasma
      using propylparaben as an internal standard. The assay was performed using a MU
      Bondapak C18 (150 mm * 4.6 mm i.d) with a mobile phase consisting of methanol and
      water (50:50), the flow rate was 1 ml/min and UV detection at 285 nm. The method
      was found to be specific for CBZ, no interfering peaks were observed with an
      overall analytical run time of 15 min. Accuracy reported as % recovery were found
      to be 98.37-100.45% and 97.53-103.58% for inter-day and intra-day accuracies,
      respectively. Inter-day precision (reproducibility) was found to be 0.53-2.75%
      RSD, while intra-day precision (repeatability) was found to be 1.06-3.7% RSD for
      the samples studied. The calibration curve was found to be linear with the
      equation y = 0.2847x + 0.0138, with a correlation coefficient of 0.9999 (R (2))
      over a concentration range of 0.5-40 MUg/ml. The limit of quantitation was the
      lowest concentration. The method is simple and rapid and does not require any
      preliminary treatment of the sample. The method was fully validated. 

PMID- 23960775
TI  - Synthesis, SAR and antibacterial activity of hybrid chloro, dichloro
      phenylthiazolyl-s-triazines.
AB  - A series of hybrid novel chloro (1a-9a) and dichloro (10b-18b) phenylthiazolyl-s
      triazine were synthesized and subsequently subjected to their antibacterial
      activity against three gram positive viz. Lactobacillus casei (NCIM-2651);
      Bacillus cereus (NCIM-2458); Staphylococcus aureus (NCIM-2120) and three gram
      negative viz Salmonella typhimurium (NCIM-2501); Escherichia coli (NCIM-2065);
      Klebsiella aerogenes (NCIM-2098). The SAR studies around the lead compound
      revealed that introduction of electron withdrawing groups and amino (-NH-) and
      mercapto (-S-) linker bridge seemed more promising towards antibacterial
      activity. Moreover, the virtual Molinspiration screenings are in compliance with
      Ghose's rule. 

PMID- 23960776
TI  - Preparation and evaluation of molecularly imprinted polymer liquid chromatography
      column for the separation of Cathine enantiomers.
AB  - In this study molecular imprinting technology was employed to prepare a specific
      affinity sorbent for the resolution of Cathine, a chiral drug product. The
      molecularly imprinted polymer (MIP) was prepared by non-covalent molecular
      imprinting with either (+) or (-)-Cathine (threo-2-amino-1-hydroxy-1-phenyl
      propane; norpseudoephedrine) as the template. Methacrylic acid and ethylene
      glycol di-methacrylate were copolymerized in the presence of the template
      molecule. The bulk polymerization was carried out in chloroform with 2,2'
      azobisisobutyronitrile as the initiator, at 5  degrees C and under UV radiation.
      The resulting MIP was ground into powders, which were slurry packed into
      analytical columns. After removal of template molecules, the MIP-packed columns
      were found to be effective for the resolution of (+/-)-Cathine racemates. The
      separation factor for the enantiomers ranged between 1.5 and 2.4 when the column
      was packed with MIP prepared with (+)-Cathine as the template. A separation
      factor ranging from 1.6 to 2.9 could be achieved from the column packed with MIP,
      prepared with (-)-Cathine as the template. Although the separation factor was
      higher with that previously obtained from reversed-phase column chromatography
      following derivatization with a chiral agent, elution peaks were broader due to
      the heterogeneity of binding sites on MIP particles and the possible non-specific
      interaction. 

PMID- 23960777
TI  - Formulation and evaluation of mefenamic acid emulgel for topical delivery.
AB  - Emulgels have emerged as a promising drug delivery system for the delivery of
      hydrophobic drugs. The objective of the study was to prepare emulgel of mefenamic
      acid, a NSAID, using Carbapol 940 as a gelling agent. Mentha oil and clove oil
      were used as penetration enhancers. The emulsion was prepared and it was
      incorporated in gel base. The formulations were evaluated for rheological
      studies, spreading coefficient studies, bioadhesion strength, skin irritation
      studies, in vitro release, ex vivo release studies, anti-inflammatory activity
      and analgesic activity. Formulation F2 and F4 showed comparable analgesic and
      anti-inflammatory activity when they compared with marketed diclofenac sodium
      gel. So, it can be concluded that topical emulgel of mefenamic acid posses an
      effective anti-inflammatory and analgesic activity. 

PMID- 23960778
TI  - The association between nonsteroidal anti-inflammatory drugs and potassium
      concentrations: A pharmacoepidemiological study in Saudi Arabia.
AB  - OBJECTIVE: Several nonsteroidal anti-inflammatory drugs (NSAIDs) have been linked
      to cardiac death. The mechanism that is responsible for this adverse effect
      appears to be ischemic insult; however, another possible mechanism involves
      hyperkalemia. The objective of the present study was to determine the feasibility
      of conducting pharmacoepidemiological studies in Saudi Arabia using refill
      prescription data to investigate the association between NSAIDs and increased
      serum potassium concentrations. METHODS: This retrospective cohort study included
      patients from an academic medical center in Riyadh, Saudi Arabia. The patients
      who were recently prescribed NSAIDs were compared to a control group of
      paracetamol users, with respect to the drugs' effects on serum potassium
      concentrations. The covariates that affected the potassium concentration or the
      use of NSAIDs were controlled for in the analysis. The studied outcome was the
      first serum potassium concentration of more than 5 mEq/L. RESULTS: A total of 184
      patients were prescribed NSAIDs (n = 101) or paracetamol (n = 83) and met the
      inclusion criteria. Compared to the control group, the patients who received
      NSAIDs were more likely to be women, were less likely to use angiotensin
      converting enzyme inhibitors, and were more likely to have lower baseline serum
      creatinine concentrations. The other baseline characteristics were similar
      between the patients in the NSAID group and the patients who received
      paracetamol. Compared to the patients who were prescribed paracetamol, those who
      were prescribed NSAIDs did not have an increased risk of hyperkalemia (odds
      ratio, 1.1, 95% confidence interval, 0.17-6.7, P = 0.95). CONCLUSION: In the
      present, small feasibility study, no increase in the risk of hyperkalemia was
      associated with NSAIDs compared to paracetamol. The present study was exploratory
      and included only a small number of patients; therefore, this study may not be
      sufficiently powered to detect small differences between the groups. Future
      studies with larger sample sizes are needed to investigate the association
      between NSAIDs and hyperkalemia.

PMID- 23960779
TI  - Synthesis, characterization and biological evaluation of dihydropyrimidine
      derivatives.
AB  - A series of dihydropyrimidines containing quinoline were prepared under
      conventional heating and microwave irradiation. The structures of newly
      synthesized compounds were established based on analytical and spectral studies.
      Further these compounds were evaluated for their antioxidant, antifungal and
      antibacterial activities. Most of the compounds showed moderate to good activity
      when compared with standard. 

PMID- 23960780
TI  - Efficacy and safety of levetiracetam in pediatric epilepsy.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of Levetiracetam (LEV) as an
      adjunctive therapy in pediatric patients with different generalized epilepsies.
      DESIGN: Chart review of 22 consecutive children age 4-19 years who were treated
      with LEV for at least 1 year was observed retrospectively. The mean dose rang of
      LEV was from 250 to 2000 mg. Data were collected on epilepsy type, seizure
      frequency, concomitant antiepileptic drug and adverse effect. RESULTS: Of the 22
      patient reviewed, 13 (59%) were boys and 9 (41%) were girls. Predominant seizure
      types were generalized tonic-clonic seizures 13 (59%) and tonic seizure 6 (27%).
      Other seizure types included myoclonic seizures 2 (9%) and focal seizure 3 (5%).
      The results showed 10 (45%) had become free of seizure for almost 7 months to 1
      year. Eight of these 10 patients (80%) had normalized EEG. Seizure frequency was
      reduced in 9 (41%) patients and 3 (14%) patients still had seizure. No side
      effects were reported related to LEV treated patients except for 1 patient.
      CONCLUSION: Our results confirm that LEV may be an effective adjunctive therapy
      in treatment of childhood epilepsy, especially tonic-clonic seizure, with
      possible no evident side effect.

PMID- 23960781
TI  - Appropriateness of anemia management in hemodialysis patients.
AB  - The anemia of end stage renal disease (ESRD) is common and often severe
      complication that can be managed successfully by erythropoiesis-stimulating
      agents (ESA) administration. AIMS: To investigate current practice of anemia
      management in hemodialysis patients and to assess the appropriateness of anemia
      management by comparing observed practice to the Kidney Disease Outcomes Quality
      Initiative (KDOQI) guideline recommendations. SETTINGS AND DESIGN: The study was
      conducted at two hemodialysis centers in Riyadh, Saudi Arabia. Data on anemia
      parameters, comorbidities, ESA dosing and iron supplementation were collected.
      The data were collected for 7 months retrospectively from April to the end of May
      2008 and prospectively from June to October 2008. Patients who were over 18 years
      of age with ESRD undergoing hemodialysis were included. Patients were excluded if
      they have cancer or receiving chemotherapy or radiotherapy. RESULTS: Data were
      collected from 87 patients. Mean Hgb value for those patients was 11.16 +/- 0.97
      g/dL. Thirty-nine patients (45%) had mean Hgb values between 11.0 and 12.0 g/dL
      the target range recommended by KDOQI guideline. The mean weekly prescribed dose
      of erythropoietin was 8099 +/- 5946 IU/Week (135 +/- 99 IU/kg/Week). Information
      on ferritin concentrations was available for 48 (55%) patients. The mean serum
      ferritin concentration for those patients was 693 +/- 420.5 ng/mL. Fifty-two
      patients had transferrin saturation (TSAT) values recorded. The mean TSAT value
      was 38.5 +/- 19.7%. CONCLUSIONS: There is an opportunity to improve anemia
      management in hemodialysis patients particularly thorough evaluation of causes of
      inadequate response rate and better monitoring and management of iron status.

PMID- 23960784
TI  - 'Okra' Hibiscus esculentus L.: A study of its hepatoprotective activity.
AB  - In the present study, an attempt has been made to validate the claimed uses of
      'Okra' Hibiscus esculentus in liver diseases. The preventive action of ethanolic
      extract of okra (EEO) against liver injury was evaluated in rodents using carbon
      tetrachloride-induced hepatotoxicity model. EEO, at 250 and 500 mg/kg body
      weight, exerted significant dose-dependent hepatoprotection by decreasing the
      CCl4-induced elevation of serum SGOT, SGPT, ALP, GGT, cholesterol, triglycerides
      and malondialdehyde (MDA) non-protein sulfhydryls (NP-SH) and total protein (TP)
      levels in the liver tissue. A significant reduction was also observed in
      pentobarbital-induced sleeping time in mice. The hepatoprotective and antioxidant
      activities of the extract are being comparable to standard silymarin. These
      findings were supported by histological assessment of the liver biopsy. The
      ability of okra extract to protect chemically induced liver damage may be
      attributed to its potent antioxidant property. 

PMID- 23960783
TI  - Knowledge, attitudes and behavior regarding antibiotics use and misuse among
      adults in the community of Jordan. A pilot study.
AB  - Factors associated with antibiotic use, resistance and safety have been well
      recognized worldwide in the literature. Nevertheless, only few studies have been
      conducted in Jordan in this area. The aim of this study was to assess knowledge,
      behavior and attitude toward antibiotics use among adult Jordanians. The study
      represents a cross sectional survey using an interviewer administered
      questionnaire. Data collected from a random sample of 1141 adult Jordanians,
      recruited at different settings, regarding their knowledge about the
      effectiveness of, resistance toward, and self medications with antibiotics
      against bacterial, viral and parasitic diseases. 67.1% believed that antibiotics
      treat common cold and cough. 28.1% misused antibiotics as analgesics. 11.9% of
      females showed inadequate knowledge about the safe use of antibiotics during
      pregnancy and nursing. 28.5% kept antibiotics at home for emergency use and 55.6%
      use them as prophylaxis against infections. 49.0% use left-over antibiotics
      without physicians' consultation while 51.8% use antibiotics based on a relative
      advice. 22.9% of physicians prescribe antibiotics over the phone and >50.0%
      routinely prescribe antibiotics to treat common cold symptoms. Our findings
      indicated that young adults showed unsatisfactory knowledge of proper antibiotic
      use. Therefore, there is an urge for educational programs using all media means. 

PMID- 23960785
TI  - A validated capillary electrophoresis method for simultaneous determination of
      ezetimibe and atorvastatin in pharmaceutical formulations.
AB  - A simple, precise, and sensitive capillary electrophoresis technique coupled with
      a diode array detector has been developed for the separation and simultaneous
      determination of ezetimibe and atorvastatin in pharmaceutical formulations.
      Separation of both ezetimibe and atorvastatin was achieved utilizing fused silica
      capillary (58 cm * 75 MUm ID) and background electrolyte solution that consisted
      of phosphate buffer (2.5 mM, pH 6.7): methanol (70:30 v/v). The proposed method
      was validated by testing its specificity, linearity, precision, accuracy,
      recovery, and detection limit/quantitation limit values. The method was linear
      over the range 2.5-50 MUg/ml for ezetimibe (r = 0.9992) and 1-100 MUg/ml for
      atorvastatin (r = 0.9999). Within-day and between-day RSD for ezetimibe and
      atorvastatin were ?5.6% and ?2.9%, respectively. The detection limit was 0.07
      MUg/ml for ezetimibe and 0.06 MUg/ml for atorvastatin. The validated method was
      successfully employed for the determination of ezetimibe and atorvastatin in
      tablets with no interfering peaks from common pharmaceutical excipients. The
      percentage recoveries of the two drugs from their tablets were 99.80 +/- 1.76 and
      100.19 +/- 1.83, respectively. 

PMID- 23960782
TI  - The immunopharmacologic potential of Semaxanib and new generation directed
      therapeutic drugs: Receptor tyrosine kinase regulation with anti
      tumorigenensis/angiogenesis properties.
AB  - Molecular signaling of messages emanating from cellular membranes through
      receptor tyrosine kinases (RTKs) is a major mechanism for intercellular
      communication and transduction during development and metabolism, as well as in
      disease-associated processes. The phosphorylation status and signaling activity
      of RTKs are determined by a dynamic equilibrium of the activity of both RTKs and
      protein tyrosine phosphatases (PTPs). RTKs are essentially a class of cell
      surface receptors for growth factors and other extracellular ligands, the most
      conspicuous perhaps are members of the vascular endothelial growth factor (VEGF)
      gene family, which plays a fundamental role in the growth and differentiation of
      vascular, as well as lymphatic endothelial cells. In particular, VEGF is a major
      regulator of normal (physiologic) and abnormal (cancerous) angiogenesis,
      including that associated with tumors and cancer. Blockers/inhibitors and
      regulators of RTKs are indeed promising cancer interventions, their specific
      mechanisms are yet to be unraveled. In this cutting-edge synopsis, I elaborate on
      breakthroughs/advances and current concepts of RTK regulation, further shedding
      light on exploring the role of potential regulators, particularly the RTK
      inhibitor Semaxanib, and the mechanisms associated with tumorigenesis in an
      effort to understand a potentially alleviating pharmacologic therapeutic
      intervention. This survey also tackles the loopholes and shortcomings of the
      aforementioned inhibitory role of Semaxanib, especially its inefficacy and
      ultimate discontinuation of relevant clinical trials. 

PMID- 23960786
TI  - Synthesis, anticonvulsant and neurotoxicity evaluation of some new pyrimidine-5
      carbonitrile derivatives.
AB  - A series of 2-[2-(substituted benzylidene) hydrazinyl]-4-(4-methoxyphenyl)-6-oxo
      1,6-dihydro-pyrimidine-5-carbonitrile (3-16) were synthesized by refluxing 2
      hydrazino-4-(4-methoxy-phenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile (2)
      with different substituted aromatic aldehydes in glacial acetic acid and absolute
      alcohol mixture (8:2). The compounds were evaluated for their anticonvulsant and
      neurotoxicity effect. In MES test compounds 2-[2-(4-bromo-benzylidene)
      hydrazinyl]-4-(4-methoxyphenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile (5),
      2-[2-(4-hydroxy-benzylidene)-hydrazinyl]-4-(4-methoxyphenyl)-6-oxo-1,6-dihydro
      pyrimidine-5-carbonitrile (9), and 2-[2-(3-fluoro-benzylidene)-hydrazinyl]-4-(4
      methoxyphenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile (16) were found to be
      highly active at a dose level of 30 mgkg(-1) at 0.5 h time interval, indicating
      their ability to prevent seizure spread at a relatively low dose. 

PMID- 23960787
TI  - Portable system of programmable syringe pump with potentiometer for determination
      of promethazine in pharmaceutical applications.
AB  - A simple and fast-automated method was developed and validated for the assay of
      promethazine hydrochloride in pharmaceutical formulations, based on the oxidation
      of promethazine by cerium in an acidic medium. A portable system, consisting of a
      programmable syringe pump connected to a potentiometer, was constructed. The
      developed change in potential during promethazine oxidation was monitored. The
      related optimum working conditions, such as supporting electrolyte concentration,
      cerium(IV) concentration and flow rate were optimized. The proposed method was
      successfully applied to pharmaceutical samples as well as synthetic ones. The
      obtained results were realized by the official British pharmacopoeia (BP) method
      and comparable results were obtained. The obtained t-value indicates no
      significant differences between the results of the proposed and BP methods, with
      the advantages of the proposed method being simple, sensitive and cost effective.

PMID- 23960788
TI  - Ethosomes and ultradeformable liposomes for transdermal delivery of clotrimazole:
      A comparative assessment.
AB  - THE OBJECTIVE OF WORK WAS TO FORMULATE, EVALUATE AND COMPARE THE TRANSDERMAL
      POTENTIAL OF NOVEL VESICULAR NANOCARRIERS: ethosomes and ultradeformable
      liposomes, containing clotrimazole (CLT), an anti-fungal bioactive. The ethosomal
      formulation (ET4) and ultradeformable liposomal (UL) formulation (TT3) showed
      highest entrapment 68.73 +/- 1.4% and 55.51 +/- 1.7%, optimal nanometric size
      range 132 +/- 9.5 nm and 121 +/- 9.7 nm, and smallest polydispersity index 0.027
      +/- 0.011 and 0.067 +/- 0.009, respectively. The formulation ET4 provided
      enhanced transdermal flux 56.25 +/- 5.49 MUg/cm(2)/h and decreased the lag time
      of 0.9 h in comparison to TT3 formulation (50.16 +/- 3.84 MUg/cm(2)/h; 1.0 h).
      Skin interaction and FT-IR studies revealed greater penetration enhancing effect
      of ET4 than TT3 formulation. ET4 formulation also had the highest zone of
      inhibition (34.6 +/- 0.57 mm), in contrast to TT3 formulation (29.6 +/- 0.57 mm)
      and marketed cream formulation (19.0 +/- 1.00 mm) against candidal species.
      Results suggested ethosomes to be the most proficient carrier system for dermal
      and transdermal delivery of clotrimazole. 

PMID- 23960789
TI  - Effect of the mode of incorporation on the disintegrant properties of acid
      modified water and white yam starches.
AB  - Acid modified starches obtained from two species of yam tubers namely white yam -
      Dioscorea rotundata L. and water yam - D. alata L. DIAL2 have been investigated
      as intra- and extra-granular disintegrants in paracetamol tablet formulations.
      The native starches were modified by acid hydrolysis and employed as disintegrant
      at concentrations of 5 and 10% w/w and their disintegrant properties compared
      with those of corn starch BP. The tensile strength and drug release properties of
      the tablets, assessed using the disintegration and dissolution (t 50 and t 80 -
      time required for 50% and 80% of paracetamol to be released) times, were
      evaluated. The results showed that the tensile strength and the disintegration
      and dissolution times of the tablets decreased with increase in the concentration
      of the starch disintegrants. The acid modified yam starches showed better
      disintegrant efficiency than corn starch in the tablet formulations. Acid
      modification appeared to improve the disintegrant efficiency of the yam starches.
      Furthermore, tablets containing starches incorporated extragranularly showed
      faster disintegration but lower tensile strength than those containing starches
      incorporated intragranularly. This emphasizes the importance of the mode of
      incorporation of starch disintegrant. 

PMID- 23960790
TI  - Severe ocular injury and its management following self induced plant extracts: A
      case report.
AB  - INTRODUCTION: Homemade and folk remedies' use is widely practiced in under
      developed countries, of the used materials are plant extracts, lemon juice and
      some dried insect bodies. CASE PRESENTATION: We report a case of severe ocular
      injury and its management after self administered plants seeds in both the eyes
      of a 47-year-old man who had bilateral severe ocular damage after he put the
      seeds of a plant Lepidium Sativum (Rashad) in his eyes. He reported severe ocular
      pain and redness, conjunctival epithelial defect and symblepharon. A conjunctival
      biopsy was taken which turned out to be negative for the immunological staining
      studies for Ocular Cicatricial Pemphegoid (OCP). The patient's visual acuity
      improved from 20/40 before treatment to 20/25 after treatment with no further
      sequelae after 3 months follow-up. CONCLUSIONS: Self induced plant extracts can
      cause ocular complications. Public awareness is necessary to help in discouraging
      the use of these harmful plant extracts in human eyes.

PMID- 23960791
TI  - Anti-tuberculosis drug-induced hepatitis in renal transplant patient with
      pulmonary and extra pulmonary tuberculosis.
AB  - Hepatotoxicity is a major side-effect of the medicines used in tuberculosis
      therapy. Although the guidelines for the management of antituberculosis drug
      induced hepatitis have been published from varieties of health institutes and
      organizations, they are to a great extent highly similar, there are nevertheless
      some important differences. We report a case of hepatitis in a renal transplant
      recipient admitted with pulmonary and extra pulmonary (abdominal) tuberculosis
      and review the literature on this topic. The introduction of antimicrobial teams,
      including specialist pharmacists, microbiologists and infectious disease
      physicians, is a major factor to improve the quality of care and faces the
      overcoming of antimicrobial resistance. Reintroducing one antituberculosis drug
      at a time with close monitoring of liver enzymes seems to be the optimal approach
      in the management of antituberculosis drug induced hepatitis. With multi
      disciplinary clinical approach the patient has been successfully cured and has
      returned to normal active life. 

PMID- 23960792
TI  - The use of pharmacoeconomic evidence to support formulary decision making in
      Saudi Arabia: Methodological recommendations.
AB  - In pharmacoeconomics the costs and consequences of alternative medications are
      compared. Many countries have begun to use pharmacoeconomic evidence to support
      decisions on licensing, pricing, reimbursement, or addition to the formulary. In
      Saudi Arabia, it is not mandatory to submit cost effectiveness evidence to
      support licensing or addition to the formulary decisions however, data will be
      considered if submitted. Previous evidence suggests that the use of
      pharmacoeconomic evidence by Saudi Pharmacy and Therapeutic (P&T) committee
      members in formulary decisions making process is limited mainly because of lack
      of expertise and lack of resources. This paper intended to provide Saudi P&T
      decision makers with a clear set of best practice methodological recommendations
      to help in increasing the utilisation of pharmacoeconomic evidence in the
      formulary decisions making process. 

PMID- 23960793
TI  - Practice, awareness and opinion of pharmacists toward disposal of unwanted
      medications in Kuwait.
AB  - BACKGROUND: The disposal of unwanted medications has been a concern in many
      countries, as pharmaceutical waste enters the ecosystem, ultimately having an
      effect on human health and environment. Earlier studies in Kuwait found that the
      method of disposal by the public was by disposing in the garbage or by flushing
      down the drain. In accordance with patient preference and environment safety, it
      would be appropriate to use local government pharmacies as collection points for
      proper disposal. OBJECTIVE: To determine the practice of pharmacists, working in
      government healthcare sectors, with regard to disposal of returned unwanted
      medications by the public. This study also aims to assess pharmacists' awareness
      toward the impact of improper disposal on the environment and to investigate
      whether pharmacists agree to have their pharmacies as collection points for
      future take-back programs. METHOD: A random sample of 144 pharmacists from the
      six main governmental hospitals and 12 specialized polyclinics in Kuwait,
      completed a self-administered questionnaire about their practice of disposal,
      awareness and opinion on using pharmacies as collection points for proper
      disposal of UMs. Data were analyzed using descriptive statistics. RESULTS: A
      total of 144 pharmacists completed the survey. Throwing UMs in the trash was the
      main method of disposal by majority of the respondents (73%). Only 23 pharmacists
      disposed UMs according to the guidelines of Ministry of Health, Kuwait (MOH).
      However, about 82% are aware that improper disposal causes damage to the
      environment and 97% agree that it is their responsibility to protect the
      environment. About 86-88% of the pharmacists agree to have government hospital
      pharmacies and polyclinics as collection points for future take-back programs.
      CONCLUSION: Even though the current practice of disposal by majority of
      pharmacists is inappropriate, they are aware of the damage and acknowledge their
      responsibilities toward environment protection. Concerned authorities should
      monitor and implement proper disposal guidelines in all pharmacies. Majority of
      pharmacists support the idea of having the government pharmacies as collection
      points for safe disposal of UMs in Kuwait.

PMID- 23960794
TI  - Hospital pharmacy practice in Saudi Arabia: Prescribing and transcribing in the
      Riyadh region.
AB  - PURPOSE: The purpose of this survey is to outline pharmacy services in hospitals
      on a regional level in the Kingdom of Saudi Arabia. METHODS: A modified-American
      Society of Health-System Pharmacists (ASHP) survey questionnaire as pertinent to
      Saudi Arabia was used to conduct a national survey. After discussing with the
      pharmacy directors of 48 hospitals in the Riyadh region over the phone on the
      survey's purpose, the questionnaires were personally delivered and collected upon
      completion. The hospital lists were drawn from the Ministry of Health hospital
      database. RESULTS: Twenty-nine hospitals participated in the survey giving a
      response rate of 60.4%. Approximately 60% of the hospitals which participated in
      the survey required prior approval for the use of non-formulary medications.
      About 83.3% of hospitals reviewed compliance with clinical practice guidelines
      and 72.7% hospitals reported that pharmacists are also actively involved in these
      activities. Pharmacists in more than 95% of hospitals provided consultations on
      drug information. A staff pharmacist routinely answering questions was the most
      frequently cited (74.1%) method by which objective drug information was provided
      to prescribers. Electronic drug information resources were available in 77.7% of
      hospitals, although internet use is not widely available to hospital pharmacists,
      with only 58.6% of hospitals providing pharmacist access to the internet. About,
      34.5% of hospitals had computerized prescriber order entry (CPOE) systems with
      clinical decision-support systems (CDSSs) and 51.9% of the hospitals had
      electronic medical record (EMR) system. CONCLUSION: Hospital pharmacists are
      increasingly using electronic technologies to improve prescribing and
      transcribing of medications in Saudi Arabia.

PMID- 23960795
TI  - The usefulness and scientific accuracy of private sector Arabic language patient
      drug information leaflets.
AB  - BACKGROUND: Inadequate access to useful scientifically accurate patient
      information is a major cause of the inappropriate use of drugs resulting in
      serious personal injury and related costs to the health care system. The
      definition of useful scientifically accurate patient information for prescription
      drugs was accepted by the US Secretary of the Department of Health and Human
      Services in 1996 as that derived from or consistent with the US FDA approved
      professional product label for a drug. Previous quality content studies found
      that English language patient drug information leaflets distributed by US
      pharmacies failed to meet minimum criteria defining useful and scientifically
      accurate information. METHOD AND FINDINGS: Evaluation forms containing the
      explicit elements that define useful scientifically accurate information for
      three drugs with known serious adverse drug reactions were created based on the
      current US FDA approved professional product labels. The Arabic language patient
      drug information leaflets for celecoxib, paroxetine, and lamotrigine were
      obtained locally and evaluated using a methodology similar to that used in
      previous quality content patient drug information studies in the US. The Arabic
      leaflets failed to meet the definition of useful scientifically accurate
      information. The celecoxib leaflet contained 30% of the required information and
      the paroxetine and lamotrigine leaflets contained 24% and 20%, respectively.
      There are several limitations to this study. The Arabic leaflets from only one
      commercial North American vendor were evaluated and the evaluation included a
      limited number of drugs. A larger study is necessary to be able to generalize
      these results. CONCLUSIONS: The study results are consistent with those of
      previous quality content studies of commercially available English patient drug
      information leaflets. The results have important implications for patients as
      access to a reliable source of drug information may prevent harm or limit the
      suffering from serious adverse drug reactions.

PMID- 23960796
TI  - Evaluation of applying drug dose adjustment by physicians in patients with renal
      impairment.
AB  - OBJECTIVE: To determine whether appropriate dose adjustment was taken into
      account or not by the physicians when prescribing drugs in patients with renal
      impairment. DESIGN: A retrospective chart review was performed and included 98
      adult in-patients, diagnosed with renal impairment based on clinical evaluation
      and laboratory data, in King Abdulaziz University Hospital (KAUH), Jeddah, Saudi
      Arabia, who was admitted to the hospital from September 2005 to January 2011.
      Data of the patients were noted and recorded including baseline demographics,
      clinical data, laboratory data, renal state, treatment data and medications.
      RESULTS: The initial number of the patients was reduced to 80 where a total of
      502 drugs were investigated in the present study with an average of six drugs per
      patient. Of these 502 studied drugs, 196 (39%) required dose adjustment where 92
      (46.9%) were adjusted and 104 (53.1%) were not adjusted. It was found also that
      most of the drugs requiring dose adjustment were antibiotics (39.8%). CONCLUSION:
      The current study confirms that physicians still do not take into account
      sufficiently patients' renal function when prescribing drugs. Continuous medical
      education and collaboration with clinical pharmacist should be encouraged for
      quality improvement in patients with renal impairment.

PMID- 23960797
TI  - Use of the single cell gel electrophoresis (comet assay) for comparing apoptotic
      effect of conventional antibodies versus nanobodies.
AB  - The large molecular size of antibodies is considered one major factor preventing
      them from becoming more efficient therapeutically. It is well established that
      all camelids have unique antibodies circulating in their blood called heavy-chain
      antibodies (HcAbs). Unlike antibodies from other species, these HcAbs contain a
      single variable domain and two constant domains (CH2 and CH3). HcAbs are a novel
      type of immunoglobulin-like, antigen binding protein with beneficial
      pharmacokinetic properties that are ideally suited to targeting cellular antigens
      for molecular imaging or therapeutic purposes. Since the antigen-binding site of
      dromedary HcAb is comprised in one single domain, it was referred to as nanobody.
      In the present work, the different IgG subclasses from immunized camel (Camelus
      dromedairus) were purified employing their different affinity for protein A
      column (PA) and protein G column (PG). Characterization of IgG subclasses was
      done by using 12% SDS-PAGE under reducing conditions. Protein bands were
      visualized after staining with Coomassie Brilliant Blue, showing two bands at 50
      kDa and 30 kDa in case of IgG1 while IgG2 and IgG3 produce only one band at 46
      kDa and 43 kDa respectively. The induction of apoptosis by either conventional or
      nanobodies was evaluated on two different cell lines, Colon and Hepatic cancer
      cell (HCT116 and HepG2), using the comet assay. Induced apoptosis were confirmed
      by visualizing DNA fragmentation bands on 2% agarose gel, and the gel was
      photographed under UV light. This study demonstrates the successful targeting of
      human cancer colon cell lines by nanobodies in vitro. It may open perspectives
      for their future use as tumor target vehicle, due to their small size, soluble
      behavior and they interact with epitopes that are less antigenic for conventional
      antibodies. 

PMID- 23960798
TI  - Simultaneous determination of retinoic acid and hydroquinone in skin ointment
      using spectrophotometric technique (ratio difference method).
AB  - An innovative spectrophotometric method was developed for simultaneous
      determination of compounds with interfering spectra in binary mixtures without
      previous separation, showing significant advantages over the conventional methods
      regarding minimal data manipulation and applicability. The proposed method was
      applied for the determination of retinoic acid and hydroquinone in laboratory
      prepared mixtures with mean percentage recoveries 100.13 +/- 0.31 and 99.99 +/-
      0.04, respectively, and in their pharmaceutical formulation with mean percentage
      recoveries 100.13 +/- 0.86 and 100.07 +/- 0.58, respectively. The method was
      validated according to USP guidelines and can be applied for routine quality
      control testing. 

PMID- 23960799
TI  - Synthesis and evaluation of chitosan-graft-poly (2-hydroxyethyl methacrylate-co
      itaconic acid) as a drug carrier for controlled release of tramadol
      hydrochloride.
AB  - Chitosan-graft-poly (2-hydroxyethyl methacrylate-co-itaconic acid) has been
      synthesized for different feed ratios of 2-hydroxyethyl methacrylate and itaconic
      acid and characterized by FT-IR, thermogravimetry and swelling in simulated
      biological fluids (SBF) and evaluated as a drug carrier with model drug, tramadol
      hydrochloride (TRM). Grafting decreased the thermal stability of chitosan. FT-IR
      spectra of tablet did not reveal any molecular level (i.e. at <10 nm scale) drug
      polymer interaction. But differential scanning calorimetric studies indicated a
      probable drug-polymer interaction at a scale >100 nm level. The observed
      Korsmeyer-Peppas's power law exponents (0.19-1.21) for the in vitro release
      profiles of TRM in SBF and other drugs such as 5-fluorouracil (FU), paracetamol
      (PCM) and vanlafaxine hydrochloride (VNF) with the copolymer carriers revealed an
      anomalous drug release mechanism. The decreased release rates for the grafted
      chitosan and the enhanced release rate for the grafts with increasing itaconic
      acid content in the feed were more likely attributed to the enhanced drug-matrix
      interaction and polymer-SBF interactions, respectively. The different release
      profiles of FU, PCM, TRM and VNF with the copolymer matrix are attributed to the
      different chemical structures of drugs. The above features suggest the graft
      copolymer's candidature for use as a promising oral drug delivery system. 

PMID- 23960800
TI  - Development of Clinical Pharmacy services at King Khalid University Hospital and
      its impact on the quality of healthcare provided.
AB  - Clinical Pharmacy is a unique service provided by the leading pharmacy
      departments in the United States. The concept of Clinical Pharmacy evolved after
      the significant increase in number of pharmaceuticals in the market and the
      increasing potential of drug interactions. However, the Clinical Pharmacist is
      not merely an individual who advises on drug interactions. There are a number of
      functions which include but are not limited to; the design of appropriate drug
      therapy, such as Pharmacokinetic assessment and evaluation to optimize drug
      therapy, drug information dissemination to the physicians and other healthcare
      providers and participation as a toxicology consultant in Poison management. At
      the King Khalid University Hospital (KKUH) the first Clinical Pharmacy services
      program began in 1983. The aim of this study is to evaluate the impact of our
      Clinical Pharmacy program on the patients' care as well as its perception by the
      Medical staff that came from different parts of the world. Our Clinical
      Pharmacists were asked to record any suggestions or interventions in the form.
      The forms were all collected at the end of each day and entered into a database
      for analysis. Each intervention was analyzed in order to assess the merit of the
      action in terms of the therapeutic, financial and direct cost impact. The study
      showed a positive impact on the patients' care as well as on the economy of the
      drugs prescribed. Meanwhile, the service was very much appreciated by the Medical
      staff as well as other healthcare providers. 

PMID- 23960801
TI  - Transient synovitis of the hip as a complication of chickenpox in infant: Case
      study.
AB  - Chickenpox has many rare complications; transient synovitis is one of the very
      painful and self-limiting rare complications. This patient suffered from
      transient synovitis associated with chickenpox. After being diagnosed, it was
      managed by diclofenac sodium suppositories. Physicians must be able to correlate
      all of the possible complications of chickenpox in order to avoid misdiagnoses. 

PMID- 23960802
TI  - Increased importance of the documented development stage in process validation.
AB  - Current trends in pharmaceutical quality assurance moved when the Federal Drug
      Administration (FDA) of the USA published its new guideline on process validation
      in 2011. This guidance introduced the lifecycle approach of process validation.
      In this short communication some typical changes from the point of view of
      practice of API production are addressed in the light of inspection experiences.
      Some details are compared with the European regulations. 

PMID- 23960803
TI  - Assessment of foetal risk associated with 93 non-US-FDA approved medications
      during pregnancy.
AB  - Health care practitioners utilize the United States-Food and Drug Administration
      (US-FDA) pregnancy categorization (A, B, C, D, X) for making decision on the
      appropriateness of certain medications during pregnancy. Many non US-FDA approved
      medications are registered and marketed in Saudi Arabia. However, these
      medications do not have an assigned pregnancy risk categorization like those
      approved in the US. The objective of this review is to evaluate, report, and
      categorize the foetal risk associated with non-US-FDA approved medications
      registered by the Saudi Food and Drug Authority (S-FDA) according to the US-FDA
      pregnancy risk categorization system. We identified 109 non-US-FDA approved
      medications in the Saudi National Formulary (SNF) as of October 2007. We searched
      for data on functional or anatomical birth defects or embryocidal-associated risk
      using different databases and references. An algorithm for risk assessment was
      used to determine a pregnancy risk category for each medication. Out of 93
      eligible medications, 73% were assigned category risk C, 10 medications (11%)
      were assigned category risk D, and 12 medications (13%) were assigned category
      risk B. Only three medications were judged to be safe during pregnancy based on
      the available evidence and were assigned category risk A. Inconsistencies in
      defining and reporting the foetal risk category among different drug regulatory
      authorities could create confusion and affect prescribing. We believe that
      standardization and inclusion of this information in the medication package
      insert is extremely important to all health care practitioners. 

PMID- 23960804
TI  - Adverse drug reactions caused by methotrexate in Saudi population.
AB  - AIM: The aim of this study is to document adverse drug reactions (ARDs) of
      methotrexate (MTX) in Saudi patients. METHODS: Cross sectional study of adult
      patients on MTX, attending rheumatology drug monitoring clinics in a university
      hospital, over a period of 24 weeks. Adverse drug reactions were sought by
      patient interview, files review and laboratory abnormalities. RESULTS: Data
      collected included patients' demographics, diagnoses, co-morbidities, MTX dose
      and duration, other medications, laboratory abnormalities and adverse reactions,
      their severity, preventability, and outcome. Out of a total of 593 patients
      screened, 186 (31.4%) using MTX were interviewed. Most of the patients were
      female (88.5%). Adverse drug reactions (ADRs) were detected in 61 patients
      (32.8%). Patients with ADRs took a mean dose of 12.9 mg (2.5-22.5 mg). Ten ADRs
      (16.4% of total reactions) were preventable; they ranged between severe, moderate
      and mild. The most common ADRs were gastrointestinal (GI) (52.5%), followed by
      anemia (8.2%) and chest tightness (6.6%). The duration of the reaction ranged
      from few hours to 4 years. CONCLUSION: In conclusion our patients with adverse
      reactions were younger, took less medications and had less co-morbidities. Our
      results were different from those published in the literature relating MTX
      toxicity.

PMID- 23960805
TI  - Hospital pharmacy practice in Saudi Arabia: Dispensing and administration in the
      Riyadh region.
AB  - BACKGROUND: There is very little published data assessing hospital pharmacy
      practice in Saudi Arabia. Hence, a comprehensive survey has been undertaken to
      evaluate hospital pharmacy services of the Kingdom of Saudi Arabia. Recently, we
      published the survey results on the prescribing and transcribing steps of the
      medication use process. This paper focuses on dispensing and administration.
      METHODS: A modified-American Society of Health-System Pharmacists (ASHP) survey
      questionnaire was personally delivered to the pharmacy directors of 48 hospitals
      in the Riyadh region. Three attempted follow-ups were made within 3 months to non
      responders and the surveys were collected upon completion. The survey was
      conducted using similar methods to those of the ASHP surveys. RESULTS: Twenty
      nine hospitals participated in the survey with a response rate of 60.4%.
      Centralized distribution (74%) is the most commonly used model for inpatient
      pharmacies. Overall, 21% of hospitals routinely use bar coding technology in
      medication dispensing. None of the hospitals are using a robotic distribution
      system to automate the dispensing of unit doses. Automated dispensing cabinets
      (ADCs) are used by 21% of hospitals as part of their decentralized distribution
      model. Sixty-one percent of hospital pharmacies have IV admixture preparation
      area in their facility. In the use of safety technology for medication
      administration, only one third of hospitals are using electronic medication
      administration records (eMARs), 7.4% had bar-code-assisted medication
      administration (BCMA) and 12% had smart infusion pumps. CONCLUSION: Hospital
      pharmacies in the Riyadh region are fairly well developed in providing dispensing
      and administration services. Further improvement can be achieved by increasing
      the use of new technologies such as bar-code technology, unit dose drug
      distribution systems, pharmacy-based IV admixture services, smart infusion pumps,
      and automated medication distribution.

PMID- 23960806
TI  - The utilization of Arabic online drug information among adults in Saudi Arabia.
AB  - In Saudi Arabia, the utilization of the world wide web has become increasingly
      popular. However, the exact figure of such use is unknown. This study aimed to
      determine the percentage of, and experience with, online Arabic drug information
      by Arabic-speaking adults in Saudi Arabia. A web based questionnaire was used.
      The questionnaire language was Arabic. Public were invited to participate in the
      survey through e-mails, Twitter, WhatsApp and Facebook in March 2012. The survey
      included 17 items examining the types of accessed Arabic drug information, the
      respondent's demographics, their ability to easily find and understand Arabic
      drug-related information, and their trustfulness and dependency on such
      information websites. Of the 422 Arabic speaking adults who answered the
      questionnaire, 88% stated that they used Arabic websites to answer drug-related
      questions. Of the respondents, 50% had a bachelor's degree, 44% were young
      adults, over half were female (60%), and 72% of them have a chronic disease. The
      ease of retrieving online information was the most common reason (69%) for
      consulting such websites. Google as a search engine was the most frequently (86%)
      accessible website. Although respondents reported different drug-related topics
      in their online searching, the search for adverse effects was the most common
      (68%). Respondents claimed that they could easily find (65%) and understand (49%)
      the drug-related information. Although a good number of respondents qualified
      this type of information as good, double-checking of information on other
      websites was highly recommended. Trustfulness was one of the important parameters
      to measure and 205 respondents (55%) claimed that they only trusted half of the
      information cited. Moreover, around 48% of respondents considered that finding
      the same information on more than one website increased its trustfulness.
      Surprisingly, 54% of respondents did not depend on Arabic information websites
      when making decisions on drug use. There are a high proportion of Arabic speaking
      people in Saudi Arabia using and consulting Arabic drug information websites.
      This information is easily found and understood. However, the quality and
      trustfulness of such websites are not high enough to depend on them. A qualified
      Arabic drug information website is important to meet this need. 

PMID- 23960807
TI  - Patients' perception, views and satisfaction with pharmacists' role as health
      care provider in community pharmacy setting at Riyadh, Saudi Arabia.
AB  - OBJECTIVES: This study will provide guiding information about the population
      perception, views and satisfaction with pharmacist's performance as health care
      provider in the community pharmacy setting in Riyadh, Saudi Arabia. METHOD: The
      study was conducted in Riyadh, Saudi Arabia, from July through December 2010. A
      total of 125 community pharmacies in Riyadh city were randomly selected according
      to their geographical distribution (north, south, east, and west). They represent
      about 10-15% of all community pharmacies in the city. The questionnaire composed
      of 8 items about patients' views and satisfaction with the pharmacists' role in
      the current community pharmacy practice. The questionnaire was coded, checked for
      accuracy and analyzed using the Statistical Package for Social Sciences (SPSS)
      version 17.0 for Windows (SPSS Inc., Chicago, Illinois). RESULTS: The response
      rate was almost 85% where 2000 patients were approached and 1699 of them
      responded to our questionnaire. The majority of respondents is young adults and
      adults (82.8%), male (67.5%) and married (66.9%). Seventy one percent of
      respondents assured that community pharmacist is available in the working while
      only 37.3% of respondents perceived the pharmacist as a mere vendor. About 38%
      assured sou moto counseling by the pharmacist, 35% reported pharmacist plays an
      active role in their compliances to treatments, 43% acknowledged the role of
      pharmacist in solving medication related problems, 34% considered the pharmacist
      as a health awareness provider and 44.6% felt that pharmacist is indispensable
      and an effective part of the health care system. CONCLUSION: The image and
      professional performance of community pharmacist are improving in Saudi Arabia.
      The Saudi patients show better satisfaction, perception and appreciation of the
      pharmacists' role in the health care team. However, extra efforts should be paid
      to improve the clinical skills of the community pharmacists. Community
      pharmacists need to be able to reach out to patient, assess their hesitations and
      promptly offer solution which was appreciated by the patients as the survey
      indicates. They should play a pro-active role in becoming an effective and
      indispensable part of health care. Furthermore, they should be able to advice,
      guide, direct and persuade the patient to comply correct usage of drugs. Finally,
      community pharmacists should equip themselves with appropriate knowledge and
      competencies in order to tender efficient and outstanding pharmaceutical health
      care.

PMID- 23960808
TI  - Loss of orally administered drugs in GI tract.
AB  - The aim of this review is to provide a broad perspective on intestinal absorption
      and the impact of intestinal first-pass metabolism on both clearance and drug
      drug interaction prediction along with its historical perspectives. The review
      also considers abilities to bridge the gap between the increasing amount of
      intestinal in vitro data and the importance of intestinal first-pass metabolism
      in vivo. The significance of efflux transporters on the intestinal absorption is
      also discussed. 

PMID- 23960809
TI  - Incidence of Helicobacter pylori infection and their clarithromycin-resistant
      strains in otitis media with effusion regarding phenotypic and genotypic studies.
AB  - Helicobacter pylori (H. pylori) are pathogenic bacteria that infect a half of the
      human population, colonize gastric mucosa and can be found in gastric juice.
      Reflux of gastric juice has been suggested to be associated with glue ear in
      children. It has been suggested that tonsil and adenoid tissues are potential
      reservoirs of H. pylori infection. These observations raise the question as to
      whether H. pylori infection might have a role in otitis media with effusion (OME)
      in children. The objectives of this research were to evaluate the incidence and
      possible role of H. pylori in the pathogenesis of OME in children and to evaluate
      the clarithromycin-resistant strains. Molecular assessment was done to evaluate
      the culture results vs. molecular study. A total of 60 children, who were prone
      to ventilation tube insertion, adenoidectomy and/or tonsillectomy were included
      in the study. The control group consisted of 40 children who underwent
      adenoidectomy and/or tonsillectomy without the history of OME. Samples of the
      middle ear fluid and mucosa, adenoid tissue, tonsillar tissue and gastric lavage
      were cultured and underwent polymerase chain reaction (PCR) analysis then were
      assembled by using QIAxcel System as capillary electrophoresis for H. pylori
      detection. There was significant difference between the results of cultures and
      PCR (P < 0.05). Middle ear fluid culture was positive for H. pylori in 40% of the
      patients vs. 56.7% PCR results while middle ear mucosa culture was positive in
      20% vs. 26.7% PCR results. Gastric lavage culture was positive in 46.6% of the
      patients and PCR was positive in 63.3% of the patients. Adenoid culture and PCR
      were positive in 56.3% for each, while tonsil culture was positive in 70% and PCR
      was positive in 90%. H. pylori presence in the gastric lavage, the tonsillar and
      adenoid tissues by culture and PCR was significantly more frequent in the study
      group compared to the control group. The minimum inhibitory concentration (MIC)
      values of clarithromycin-resistant isolates ranged from 1.5 to 8 MUg/ml. This
      study showed the presence of H. pylori in around 50% of the patients with OME.
      PCR revealed its sensitivity than culture techniques. The incidence of
      clarithromycin resistance was found to be high among the isolates (39.6%). 

PMID- 23960810
TI  - Formulation, optimization and evaluation of transferosomal gel for transdermal
      insulin delivery.
AB  - The present study deals with the development of transferosomal gel containing
      insulin by reverse phase evaporation method for painless insulin delivery for use
      in the treatment of insulin dependent diabetes mellitus. The effect of
      independent process variables like ratio of lipids (soya lecithin:cholesterol),
      ratio of lipids and surfactants, and ratio of surfactants (Tween 80:sodium
      deoxycholate) on the in vitro permeation flux (MUg/cm(2)/h) of formulated
      transferosomal gels containing insulin through porcine ear skin was optimized
      using 2(3) factorial design. The optimal permeation flux was achieved as 13.50 +/
      0.22 MUg/cm(2)/h with drug entrapment efficiency of 56.55 +/- 0.37% and average
      vesicle diameter range, 625-815 nm. The in vitro insulin permeation through
      porcine ear skin from these transferosomal gel followed zero-order kinetics (R
      (2) = 0.9232-0.9989) over a period of 24 h with case-II transport mechanism. The
      in vitro skin permeation of insulin from optimized transferosomal gel by
      iontophoretic influence (with 0.5 mA/cm(2) current supply) also provided further
      enhancement of permeation flux to 17.60 +/- 0.03 MUg/cm(2)/h. The in vivo study
      of optimized transferosomal gel in alloxan-induced diabetic rat has demonstrated
      prolonged hypoglycemic effect in diabetic rats over 24 h after transdermal
      administration. 

PMID- 23960811
TI  - Preventive effect of Metformin against N-nitrosodiethylamine-initiated
      hepatocellular carcinoma in rats.
AB  - Effect of Metformin in chemically induced hepatocarcinogenesis was assessed in
      Wistar rats. Intraperitoneal administration of chemical carcinogen diethyl
      nitrosamine (DENA) (200 mg/kg) in single dose elevated the levels of serum
      glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase
      (SGPT), alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG)
      and reduced high density lipoproteins (HDL), total proteins (TPR) and blood
      glucose level in tested animals. Histopathological examinations of the liver
      tissue showed marked carcinogenicity of the chemical carcinogen. Food and water
      intake, animal weights and serum albumin (ALB) were also assessed. The animals
      exposed to DENA showed a significant decrease in the body weights and, there were
      no significant alterations found in the total bilirubin (TBR) levels and gamma
      glutamyltranspeptidase (GGTP), whereas the decreased levels of serum ALB were
      maintained by Metformin treatment. The elevated levels of serum SGOT, SGPT, ALP,
      AFP, TC and TG were restored by administration of Metformin in reduced dose (125
      mg/kg) daily for 16 weeks p.o. Physiological and biochemical analysis showed the
      beneficial effects of Metformin in the animals exposed to DENA. 

PMID- 23960812
TI  - Phytochemical and biological studies of Solanum schimperianum Hochst.
AB  - Chemical reinvestigation of the aerial parts of Solanum schimperianum Hochst led
      to the isolation of ten compounds, lupeol (1), beta-sitosterol (2), beta
      sitosterol glucoside (3), oleanolic acid (4), teferidin (5), teferin (6),
      ferutinin (7), 5-hydroxy-3,7,4'-trimethoxyflavone (8), retusin (9) and kaempferol
      3-O-beta-d-glucopyranoside (10). Compounds 5-7 were isolated for the first time
      from Solanaceae and compounds 1-4 and 8-9 for the first time from Solanum
      schimperianum. The structure elucidation of the isolated compounds was based on
      careful inspection of spectral data including 1D ((1)H and (13)C NMR), 2D ((1)H-H
      COSY, HMQC and HMBC, ROESY), UV, MS and IR, in addition to, comparison with
      literatures. The antimicrobial activity of the extracts as well as the isolated
      compounds was tested. Only hexane extract showed activity against Bacillus
      subtilus and Staphylococcus aureus. 

PMID- 23960813
TI  - The US FDAs withdrawal of the breast cancer indication for Avastin (bevacizumab).
AB  - On November 18, 2011, the US Food and Drug Administration (US FDA) announced that
      breast cancer indication for Avastin (bevacizumab) had been withdrawn after
      concluding that the drug has not been shown to be safe and effective for the
      treatment of breast cancer. The specific indication that was withdrawn was for
      the use of bevacizumab in metastatic breast cancer, with paclitaxel for the
      treatment of patients who have not received chemotherapy for metastatic HER2
      negative breast cancer. The US FDAs decision has been met with emotion and
      confusion among the public and health professionals. The purpose of this article
      is to review the regulatory history of bevacizumab for breast cancer and to
      examine the scientific evidence that led to the approval and subsequent
      withdrawal of this indication. Bevacizumab also provides the opportunity to
      illustrate the value of free publicly available US FDA reviews that may contain
      rigorously reviewed unpublished data and analyses and to contrast the decisions
      made in the US and Europe about bevacizumab and breast cancer. 

PMID- 23960814
TI  - Quinoline: A versatile heterocyclic.
AB  - Quinoline or 1-aza-naphthalene is a weak tertiary base. Quinoline ring has been
      found to possess antimalarial, anti-bacterial, antifungal, anthelmintic,
      cardiotonic, anticonvulsant, anti-inflammatory, and analgesic activity. Quinoline
      not only has a wide range of biological and pharmacological activities but there
      are several established protocols for the synthesis of this ring. The article
      aims at highlighting these very diversities of the ring. 

PMID- 23960815
TI  - Dispensing medications without prescription at Saudi community pharmacy: Extent
      and perception.
AB  - OBJECTIVE: To investigate the dispensing behavior of pharmacists in retail
      pharmacy practice and to assess their attitude toward dispensing non-OTC drugs
      and scrutinize the causes of their malpractice; if in fact was perceived. METHOD:
      Between December 2010 and January 2011 retail pharmacies in Jeddah-KSA were
      visited randomly by a number of voluntary collaborators who played the role of
      asking for one or more of the following medications without providing a
      prescription: Co-amoxiclav (Augmentin) or Cefaclor (Ceclor), Captopril (Capoten)
      and Fluoxetine (Prozac). RESULTS: A total of 60 pharmacies were randomly included
      in this study; 100% of the pharmacists working were male, 96.7% of them were non
      Saudis and only 2 (3.3%) were Saudis. In a total of 119 drug requests, almost all
      pharmacists (97.9%) handed out the antibiotic immediately, 100% dispensed
      captopril and 89.5% gave the antipsychotic simply by following the collaborator's
      request without even asking for a doctor's prescription. In the second part of
      the study (where a mini-questionnaire is administered), 85% of the pharmacists
      agreed to answer the mini-questionnaire, and 15% refused to participate. The
      highest reason given for their wrongdoing, was for that if the pharmacist did
      not, others - of neighboring pharmacies - would do the same, followed by that
      there is no available OTC list. CONCLUSION: The study confirmed that pharmacists
      are still violating the law, which is leading to a profound malpractice in retail
      pharmacies around the country. Consequently, regulations should be reviewed and
      structured educational campaigns are a must to both pharmacists and public. The
      OTC list should be generated, implemented, and monitored by Saudi regulators and
      penalize violators.

PMID- 23960816
TI  - A survey of therapeutic drug monitoring services in Malaysia.
AB  - In Malaysia, therapeutic drug monitoring (TDM) service was started in the 1980s.
      Since then, the number of hospitals that offer the service has increased. In this
      paper, we report the findings of a nationwide survey describing the practice of
      TDM in these hospitals. Questionnaires were mailed to 128 government hospitals.
      Data were collected for general characteristics of the hospitals, administrative,
      and laboratory activities related to TDM service. One hundred and twenty-one
      hospitals responded to the survey. Thirty-four hospitals (28.1%) provided the
      service with their own TDM laboratories, 44 hospitals (36.4%) provided the
      service using other hospitals' laboratories and 43 hospitals (35.5%) did not
      provide the service at all. TDM services were more likely to be offered in larger
      hospitals with various medical specialties. Since it is managed entirely by
      hospital pharmacists, these pharmacists assume an important role in ensuring
      optimum use of the TDM service. 

PMID- 23960817
TI  - Knowledge and attitude of school children in Amman/Jordan toward the appropriate
      use of medicines: A cross-sectional study.
AB  - OBJECTIVES: The aim of this study is to examine the knowledge, practice, and
      attitude toward medications of different primary school children at age group (7
      9) years. METHODS: This cross sectional study adopted the form of structured
      interviewing technique using a validated and pre-piloted questionnaire. The
      questionnaire consisted of a mixture of multiple choice and open-ended questions,
      15 USP pictograms and six dosage form demos. A randomized stratified target
      sample of 200 students (n = 100 of each gender), of the first, second and third
      grades from the four Amman Education Directorates was recruited. School children
      were interviewed regarding their knowledge, attitude and the way they think
      medicines should be used. RESULTS: The mean score value achieved by children in
      all the knowledge questions was 23.26 +/- 0.25 out of 32, which was considered as
      satisfactory knowledge by the research team. The most significant factors
      affecting children's knowledge (including: multiple choice questions, pictograms
      and dosage forms) were: age, school/area of residency, and the presence of a
      first-degree relative working in a medical job. The majority of participants
      (79%) stated that the taste of the medication was the main factor to prevent them
      from taking their medication. CONCLUSION: In general, school children in our
      sample have satisfactory knowledge and a generally positive attitude toward
      medicines. However, school curricula in Jordan should include more education
      regarding the effective and safe use of medicines.

PMID- 23960818
TI  - Stress-induced immune-related diseases and health outcomes of pharmacy students:
      A pilot study.
AB  - Stress in health sciences students has been studied extensively. Nevertheless,
      only few studies have been conducted on pharmacy students and nothing was done to
      compare stress effects on the immune responses of Pharmacy and Doctor of Pharmacy
      (PharmD) students. The aim of this pilot study was (1) to measure the self
      reported perceived stresses, immune-related diseases and health outcomes of
      pharmacy and PharmD students, (2) to investigate the relationship between
      perceived stresses, health outcomes and immune-related diseases and (3) to
      compare stress induced changes in the health and immune system of pharmacy and
      PharmD students. The study represents a cross sectional survey using an
      interviewer administered questionnaire about stress and students' health states
      during the fall semester of 2009/2010. At commence of this study, 222 of pharmacy
      and PharmD participant students (113 and 109 respectively) from the third and
      uppermost levels of study were picked up randomly. They were found to perceive
      stress related to program intensity, lack of exercise and social activities, bad
      nutritional routines and accommodation. Effects of increased study loads on
      students' health and immune-related diseases were more pronounced on PharmD
      students, while showing significant changes on Pharmacy students. In general,
      more than 50% of students of each program got ill several times, mainly during
      the midterm period, had cold/flu, were under medical care and had problems in
      skin and/or hair. Also, PharmD students reported relatively higher levels of
      perceived stress and lower emotional and satisfaction quality of life compared to
      Pharmacy students. Results may help to increase the awareness of students to get
      prepared to what they might face, and may enable them to reduce the program's
      negative effects. 

PMID- 23960819
TI  - Development and in vivo evaluation of gastroretentive delivery systems for
      cefuroxime axetil.
AB  - The purpose of this investigation was to design and develop gastroretentive
      dosage form for cefuroxime axetil using floating tablet approach with various
      grades of hydroxypropyl methyl cellulose. Cefuroxime axetil is known to have low
      bioavailability, short half-life and is absorbed largely from upper GIT. Sodium
      bicarbonate was used in the dosage form as a source of carbon-di-oxide to
      maintain buoyancy. In vitro dissolution study results indicated non-Fickian
      diffusion controlled drug release mechanism and was best fitted into Korsmeyer
      Peppas equation. In vivo radiographic studies conducted in five healthy human
      volunteers for optimized formulation indicated over 6 h retention of tablet in
      the stomach region. Reproducible physical parameters indicated that the current
      formulation could be easily scaled-up. 

PMID- 23960820
TI  - Emulsification/internal gelation as a method for preparation of diclofenac sodium
      sodium alginate microparticles.
AB  - Emulsification/internal gelation has been suggested as an alternative to
      extrusion/external gelation in the encapsulation of several compounds including
      non-steroidal anti-inflammatory drugs such as diclofenac sodium. The objective of
      the present study was a trial to formulate diclofenac sodium as controlled
      release microparticles that might be administered once or twice daily. This could
      be achieved via emulsification/internal gelation technique applying Box-Behnken
      design to choose these formulae. Box-Behnken design determined fifteen formulae
      containing specified amounts of the independent variables, which included
      stirring speed in rpm (X1), drug:polymer ratio (X2) and the surfactant span 80%
      (X3). The dependent variables studied were cumulative percent release after two
      hours (Y1), four hours (Y2) and eight hours (Y3). The prepared microparticles
      were characterized for their production yield, sizes, shapes and morphology,
      entrapment efficiency and Diclofenac sodium in vitro release as well. The results
      showed that the production yield of the prepared diclofenac sodium microparticles
      was found to be between 79.55% and 97.41%. The formulated microparticles
      exhibited acceptable drug content values that lie in the range 66.20-96.36%.
      Also, the data obtained revealed that increasing the mixing speed (X1) generally
      resulted in decreased microparticle size. In addition, scanning electron
      microscope images of the microparticles illustrated that the formula contains
      lower span concentration (1%) in combination with lower stirring speed (200 rpm)
      which showed wrinkled, but smooth surfaces. However, by increasing surfactant
      concentration, microspheres' surfaces become smoother and slightly porous.
      Kinetic treatment of the in vitro release from drug-loaded microparticles
      indicated that the zero order is the drug release mechanism for the most
      formulae. 

PMID- 23960821
TI  - Weight and content uniformity of lorazepam half-tablets: A study of correlation
      of a low drug content product.
AB  - The aim of this study was to investigate the degree of correlation between the
      weight and the content of spilt-halves of lorazepam 2.5 mg tablets. Weight
      variation and drug content of lorazepam half-tablets were evaluated according to
      the European Pharmacopoeia tests. Only one individual mass of the 30 half tablets
      was outside the limits of 85-115% of the average mass, but since it was within 75
      125% of the average mass, the product passed the test. Each individual content
      was between 85% and 115% of the average content (99.8% expressed as a percent to
      label claim) and within the limits of 75-125%, so the product passed the
      uniformity of content test. The correlation coefficient (r) between the weight
      and the content of split halves was found to be 0.994. The weights of split
      tablet halves appear to be directly correlated with their drug content even for a
      medication with a low drug content, thus it is recommended that pharmacists who
      split tablets into two halves, assure the weight uniformity of the resultant
      halves. Manufacturers should develop formulation and manufacturing procedures
      that ensure high degree of correlation between weight and content not only among
      the whole tablet but also among the obtained tablet halves. 

PMID- 23960822
TI  - Paclitaxel loaded carrier based biodegradable polymeric implants: Preparation and
      in vitro characterization.
AB  - The objective of this study was to develop paclitaxel (PTX) loaded poly(epsilon
      caprolactone) (PCL) based tiny implants. beta-Cyclodextrin (beta-CD) and
      polyethylene glycol (PEG 6000) were used to enhance solubility and release of the
      drug in the phosphate buffer saline pH 7.4. Implants were evaluated in terms of
      color, shape, thickness, surface area, weight, drug content. Developed implants
      were characterized for their surface morphology (SEM analysis), drug physical
      state by thermal analysis (DSC studies), crystalline nature (XRD studies) and
      drug excipients compatibility (FT-IR spectroscopy). Macroscopically all the tiny
      implants were white in color and cylindrical in shape with smooth surfaces. PTX
      was entrapped within implants in the polymeric amorphous form. In vitro drug
      release studies showed prolonged and controlled release of PTX with zero order
      and Korsmeyer-Peppas model being exhibited. Excipients and method of preparation
      did not affect chemical stability of PTX. 

PMID- 23960823
TI  - Box-Behnken supported validation of stability-indicating high performance thin
      layer chromatography (HPTLC) method: An application in degradation kinetic
      profiling of ropinirole.
AB  - Stability-indicating high-performance thin-layer chromatographic (HPTLC) method
      for the analysis of ropinirole HCl was developed and validated as per the ICH
      guidelines. The method employed the mobile phase and toluene-ethyl acetate-6 M
      ammonia solution (5:6:0.5, v/v/v) was optimized with the help of a design expert.
      Densitometric analysis of ropinirole HCl was carried out in the absorbance mode
      at 250 and 254 nm. Compact spots for ropinirole HCl were found at R f value of
      0.58 +/- 0.02. The linear regression analysis data for the calibration plots
      showed R (2) = 0.9989 +/- 0.0053 with a concentration range of 100-3000 ng spot(
      1). The method was validated for precision, accuracy, ruggedness, robustness,
      specificity, recovery, limit of detection (LOD) and limit of quantitation (LOQ).
      The LOD and LOQ were 12.95 and 39.25 ng spot(-1) respectively. Drug was subjected
      to acidic, alkaline, oxidative, dry heat, wet heat and photo degradation stress.
      All the peaks of degradation products were well resolved from the standard drug
      peak with significant difference of R f. The acidic and alkaline stress
      degradation kinetics of ropinirole, were found to be in first order, showing high
      stability (t 1/2, 146.37 h(-1); t 0.9, 39.11 h(-1)) in the acidic medium and low
      stability (t 1/2, 97.67 h(-1); t 0.9, 14.87 h(-1)) in the alkaline environment. 

PMID- 23960824
TI  - A validated stability-indicating LC method for estimation of etoposide in bulk
      and optimized self-nano emulsifying formulation: Kinetics and stability effects.
AB  - The present investigation was aimed to establish a validated stability-indicating
      liquid chromatographic method for the estimation of etoposide (ETP) in bulk drug
      and self-nano emulsifying formulation. ETP was successfully separated from the
      degradation products formed under stress conditions on LiChrospher 100 C18
      reverse-phase column (a 250 mm * 4.6 mm i.d., 5-MUm particle size) using 55:45
      (v/v) acetonitrile-phosphate buffer saline (pH 4.5) as the mobile phase, at a
      flow rate of 1.0 mL min(-1) and detection at 283 nm. The response was a linear
      function of analyte concentration (R(2) > 0.9997) over the concentration range of
      0.05-50 MUg mL(-1). The method was validated for precision, accuracy, robustness,
      sensitivity and specificity. The % recovery of ETP at three different levels
      (50%, 100% and 150%) ranged between 93.84% and 100.06% in optimized self-nano
      emulsifying formulation, Etosid(r) soft-gelatin capsule and Fytosid(r) injection.
      First-order degradation kinetics of ETP were observed under acidic and alkaline
      conditions. The method was also applied for the stability assessment of self-nano
      emulsifying formulation under accelerated conditions, the formulation was found
      to be stable at all storage conditions with the shelf-life of 2.37 years at 25 
      degrees C. The method holds promise for routine quality control of ETP in bulk,
      pharmaceutical formulations as well as in stability-indicating studies. 

PMID- 23960825
TI  - Gastroretentive hydrodynamically balanced systems of ofloxacin: In vitro
      evaluation.
AB  - Hydrodynamically balanced systems (HBSs) of ofloxacin were prepared using
      lactose, HPMC K4M, PVP K 30, and liquid paraffin, which may increase the mean
      residence time in the gastrointestinal tract, and may be able to provide maximum
      drug at the site of absorption to improve oral bioavailability. All these
      formulated HBS capsules were floated well over 6 h with no floating lag time.
      They also showed sustained drug release over 6 h. Time for 50% release of
      ofloxacin was within the range, 2.47 +/- 0.02 to 3.07 +/- 0.08 h. The in vitro
      drug release from these HBS capsules was dependent on HPMC K4M, PVP K 30, and
      liquid paraffin content. The drug release pattern of these HBS capsules
      containing ofloxacin followed the Higuchi model with the anomalous transport
      mechanism. 

PMID- 23960826
TI  - Isolation and screening of bioactive principle from Chaetomorpha antennina
      against certain bacterial strains.
AB  - Microbial pathogens develop resistance to a particular antibiotic after repeated
      administration during the treatment of infectious diseases. Moreover, multiple
      drug resistance is a very common problem especially in hospital acquired
      infections. Therefore, it is necessary to find out alternative antibacterial
      drugs and the present trend is focused on seaweeds. This preliminary research
      work was carried out to find out the antibacterial activity of petroleum ether
      extract of Chaetomorpha antennina. The extracts were tested against
      Staphylococcus aureus MTCC 121, Bacillus cereus MTCC 492, Bacillus subtilis MTCC
      441, Klebsiella pneumoniae MTCC 530, Escherichia coli MTCC 443 and Pseudomonas
      aeruginosa MTCC 779 by agar well diffusion technique. It was observed that
      petroleum ether extract showed prominent zone of inhibition against Escherichia
      coli, Pseudomonas aeruginosa and Staphylococcus aureus even at 50 MUg/ml
      concentration. The maximum spectrum of activity was observed against
      Staphylococcus aureus ranged from 7.3 +/- 0.8 to 18 +/- 2.4 mm at the
      concentration 50 to 500 MUg/ml, respectively. Hence the most susceptible
      bacterium was Staphylococcus aureus among the tested organisms. However,
      Escherichia coli and Pseudomonas aeruginosa are also susceptible. But the
      Bacillus cereus and Klebsiella pneumoniae are resistant against the tested
      extract. 

PMID- 23960827
TI  - Standard treatment guidelines for malaria: Challenges in its implementation in
      Islamabad (federal capital) and Rawalpindi (twin city), Pakistan.

PMID- 23960829
TI  - A study investigating the community pharmacist knowledge about the appropriate
      use of inhaler, Eastern Region AlAhsa, Saudi Arabia.
AB  - The current study aims to assess the community pharmacist's skills to make
      correct use of metered dose inhalers (MDIs). Seventy-four pharmacists were
      approached using six clusters from the most populous areas of Alahsa, Eastern
      region Saudi Arabia. Of whom n = 71, responses were taken in consideration to
      perform the statistical analysis. Scoring of pharmacist demonstration was done
      using a nine-step checklist for the appropriate use of inhaler. A simulated
      patient approach was used to assess pharmacist's skill. Majority, 98.6% of the
      pharmacists were Egyptian nationals with a mean age of 38.74 +/- SD 4.52.
      Overall, pharmacists were found to have a poor recognition (mean score = 4.2 +/-
      SD 2.08) with the steps considered while using an inhaler. However, significantly
      better knowledge differences were observed among the pharmacists aged 30-35 years
      (5.52 +/- 2.14, t = 2.851, p = 0.009(*)). In addition, job experience (3-4 years)
      was found significantly (p = 0.003(*)) associated with a better knowledge toward
      the appropriate use of inhaler. It was seen that the young pharmacists working on
      chain pharmacies have comparatively better knowledge than the other groups. 

PMID- 23960828
TI  - Prospects of pharmaceuticals and biopharmaceuticals loaded microparticles
      prepared by double emulsion technique for controlled delivery.
AB  - Several methods and techniques are potentially useful for the preparation of
      microparticles in the field of controlled drug delivery. The type and the size of
      the microparticles, the entrapment, release characteristics and stability of drug
      in microparticles in the formulations are dependent on the method used. One of
      the most common methods of preparing microparticles is the single emulsion
      technique. Poorly soluble, lipophilic drugs are successfully retained within the
      microparticles prepared by this method. However, the encapsulation of highly
      water soluble compounds including protein and peptides presents formidable
      challenges to the researchers. The successful encapsulation of such compounds
      requires high drug loading in the microparticles, prevention of protein and
      peptide degradation by the encapsulation method involved and predictable release,
      both rate and extent, of the drug compound from the microparticles. The above
      mentioned problems can be overcome by using the double emulsion technique,
      alternatively called as multiple emulsion technique. Aiming to achieve this
      various techniques have been examined to prepare stable formulations utilizing
      w/o/w, s/o/w, w/o/o, and s/o/o type double emulsion methods. This article reviews
      the current state of the art in double emulsion based technologies for the
      preparation of microparticles including the investigation of various classes of
      substances that are pharmaceutically and biopharmaceutically active. 

PMID- 23960830
TI  - Medication safety practices in hospitals: A national survey in Saudi Arabia.
AB  - BACKGROUND: Medication errors in hospitals are a worldwide concern. The World
      Health Organization has recommended the implementation of basic applications in
      healthcare systems to improve medication safety, but it is largely unknown
      whether these recommendations are adhered to by hospitals. We assessed the
      presence of core medication safety practices in Saudi Arabian hospitals. METHODS:
      We developed and validated a survey to assess medication safety practices in
      hospitals. Major headings included Look-Alike Sound-Alike (LASA) medications,
      control of concentrated electrolyte solutions, transitions in care, information
      technology, drug information and other medication safety practices. Trained
      pharmacists visited samples of hospitals from all regions of Saudi Arabia.
      RESULTS: Seventy-eight hospitals were surveyed. Only 30% of the hospitals had a
      medication safety committee and 9% of hospitals had a medication safety officer.
      Only 33% of hospitals had a list of LASA medications and 50% had a list of error
      prone abbreviations. Concentrated electrolytes were available in floor stock in
      60% of the hospitals. No hospital involved pharmacists in obtaining medication
      histories and only 37% of the hospitals provided a medication list to the
      patients at discharge. While 61% of hospitals used a computer system in their
      pharmacy to enter prescriptions, only 29% of these hospitals required entry of
      patient's allergies before entering a drug order. CONCLUSIONS: Core practices to
      improve medication safety were not implemented in many hospitals in Saudi Arabia.
      In developing countries, an effort must be made at the national level to increase
      the adoption of such practices.

PMID- 23960831
TI  - Hospital versus home treatment of deep vein thrombosis in a tertiary care
      hospital in Saudi Arabia: Are we ready?
AB  - AIM/BACKGROUND: Treatment of DVT with LMWHs has been shown recently to be as
      effective as UFH with suggested lower costs. This study was conducted to
      determine and compare the cost of in-patient hospital treatment versus outpatient
      hospital treatment of patients with DVT. METHOD: All adult patients with acute
      proximal DVT referred to the Emergency Department of King Khalid University
      Hospital, Riyadh, Saudi Arabia between August 2009 and August 2010 were invited
      to the study. An economic analysis was performed to compare the cost impact of
      outpatients versus hospital treatment. RESULTS: Sixty-one patients were included
      in the study, 31 were followed in the outpatient setting and 30 as the control
      group (inpatients). There were no significant differences in the outcome between
      the outpatient and inpatient group; three patients (9.7%) in the outpatient group
      and four patients (13.3%) in the inpatient group had recurrent DVT. Mean nursing
      cost was $55 for the outpatient group and $215 for the inpatient group, mean
      laboratory monitoring cost was $638 for outpatient group and $1511 for the
      inpatient group. Hospital stay and doctor's fees amounted to a mean of $1000 for
      outpatient treatment and $2387 for inpatient treatment, p < 0.0001. The mean
      outpatient cost was significantly lower than the inpatient cost ($1750 vs. $4338,
      p < 0.0001). CONCLUSION: Outpatient treatment of patients with DVT using LMWHs is
      cost-effective with no significant differences in the outcome of patients. OPD
      treatment of DVT is feasible in Saudi Arabia provided there is enough logistic
      support from thrombosis clinics and those involved in DVT care.

PMID- 23960832
TI  - A randomized, controlled trial of a clinical pharmacist intervention in
      microdiscectomy surgery - Low dose intravenous ketamine as an adjunct to standard
      therapy.
AB  - AIM: The hypothesis that postoperative pain would be reduced by using 1
      MUg/kg/min of ketamine, both intra- and post-operatively, for lumbar
      microdiscectomy surgery was assessed by measuring morphine consumption. Patient
      side effects were reported. METHODS: Forty-five patients undergoing
      microdiscectomy surgery were randomized under double-blind conditions into three
      groups: Group1 (G1) received normal saline, Group 2 (G2) ketamine (1 MUg/kg/min)
      intra-operatively and Group 3 (G3) ketamine (1 MUg/kg/min) both intra- and post
      operatively. Morphine consumption, pain scores, nausea and vomiting, CNS
      disorders were recorded for 24 h post surgery. This study was conducted by
      applying the concept of a clinical pharmacist intervention. RESULTS: The time for
      the first analgesia demand dose was significantly shorter (P < 0.05) in G117 +/-
      1.7 min than for G2 and G3. In G3 morphine consumption 6, 12, and 24 h after
      surgery was 3 +/- 2.26, 9.2 +/- 2.11 and 26.9 +/- 2.71 mg. Total morphine
      consumption was significantly lower for G3 than for G1 or G2 (P < 0.05). The
      visual analog scale score (VAS) values were significantly lower in G3 (P < 0.05)
      than for the other groups during the first 24 h. The rate of nausea and vomiting
      was significantly higher in G1 vs G3 (P < 0.05). No difference in drug induced
      CNS disturbances was observed among the groups. CONCLUSIONS: Using 1 MUg/kg/min
      of ketamine hydrochloride intra- and post-operatively for microdiscectomy surgery
      could be an adjunct therapy to reduce postoperative morphine consumption
      minimizing its side effects. Collaborative clinical pharmacy practice on the
      basis of pharmacology had an effective role in improving the general outcome of
      microdiscectomy surgery.

PMID- 23960833
TI  - Hybrid drug delivery system for oropharyngeal, cervical and colorectal cancer -
      in vitro and in vivo evaluation.
AB  - The present investigation was designed with the intention to formulate a
      versatile 5-fluorouracil(5-FU) matrix tablet surpassing issues associated with
      current conventional chemotherapeutic drug delivery systems. The novel 5-FU
      matrix tablet fulfills therapeutic needs by engineering matrix tablets utilizing
      chitosan-sodium alginate interpolyelectrolyte complex (IPEC). IPEC was
      characterized by Fourier transform infrared spectroscopy (FTIR), differential
      scanning calorimetry (DSC) and X-ray diffraction (XRD). The matrix tablets were
      formulated utilizing IPEC alone and in combination with chitosan, sodium alginate
      and sodium deoxycholate as permeation enhancer. Pharmaceutical properties,
      swelling studies, in vitro dissolution and diffusion studies, mucoadhesive
      studies and in vivo studies were performed for formulated 5-FU. The selected
      chitosan-sodium alginate IPEC offers pH independent 5-FU release in comparison to
      alone or physical mixture of chitosan and sodium alginate. Furthermore, novel
      matrix tablets demonstrated significantly higher bioadhesive properties with
      controlled 5-FU release without the initial burst effect and also demonstrated a
      higher permeation of 5-FU. To conclude, the developed novel 5-FU matrix tablets
      pave way as an excellent alternative for cancer treatment which could potentially
      minimize the dose dependent side effects and provide better patient compliance. 

PMID- 23960834
TI  - Attenuation of uremia by orally feeding alpha-lipoic acid on acetaminophen
      induced uremic rats.
AB  - Uremia means excess nitrogenous waste products in the blood & their toxic
      effects. An acute acetaminophen (paracetamol, N-acetyl p-aminophenol; APAP)
      overdose may result into potentially fatal hepatic and renal necrosis in humans
      and experimental animals. The aims of this present study were to investigate the
      protective effect of alpha-lipoic acid (ALA) on oxidative stress & uremia on male
      albino rats induced by acetaminophen. The study was performed by 24 albino male
      Wister strain rats which were randomly divided into four groups: Group I, control
      - receives normal food and water, Groups II, III & IV receive acetaminophen
      interperitoneally at the dose of 500 mg/kg/day for 10 days, from 11th day Groups
      III & IV were treated with ALA at the dose of 5 mg & 10 mg/100 g/day for 15 days,
      respectively. After 25 days of treatment, it was observed that there was a
      significant increase in plasma urea, creatinine, sodium and malondialdehyde (MDA)
      levels (p < 0.05) but a significant decrease in super oxide dismutase (SOD) &
      catalase activity & potassium level in uremic group is compared with control
      group & there was a significant increase in SOD & catalase (p < 0.05) & a
      significant decrease in serum urea, creatinine & Na and MDA (p < 0.05) in Group
      III & Group IV is compared with Group II & significant changes were observed in
      high ALA dose group. In conclusion it was observed that the ALA has
      nephroprotective activities by biochemical observations against acetaminophen
      induced uremic rats. 

PMID- 23960835
TI  - Evaluation of chemically modified hydrophobic sago starch as a carrier for
      controlled drug delivery.
AB  - The present investigation deals with the development of controlled release
      tablets of lamivudine using acetylated sago starch. The acetylated starch was
      synthesized with acetic anhydride in pyridine medium. The acetylated sago starch
      was tested for acute toxicity and drug-excipient compatibility study. The
      formulations were evaluated for physical characteristics like hardness, %
      friability, % drug content and weight variations. The in vitro release study
      showed that the optimized formulation exhibited highest correlation (R) value in
      the case of higuchi kinetic model and the release mechanism study proved that the
      formulation showed a combination of diffusion and erosion processes. There was a
      significant difference in the pharmacokinetic parameters (T max, C max, AUC, V d,
      T 1/2 and MDT) of the optimized formulation as compared to the marketed
      conventional tablet Lamivir(r) which proves the controlled release property of
      acetylated sago starch. 

PMID- 23960836
TI  - Formulation development and optimization of sustained release matrix tablet of
      Itopride HCl by response surface methodology and its evaluation of release
      kinetics.
AB  - The objective of this present investigation was to develop and formulate
      sustained release (SR) matrix tablets of Itopride HCl, by using different polymer
      combinations and fillers, to optimize by Central Composite Design response
      surface methodology for different drug release variables and to evaluate drug
      release pattern of the optimized product. Sustained release matrix tablets of
      various combinations were prepared with cellulose-based polymers: hydroxy propyl
      methyl cellulose (HPMC) and polyvinyl pyrolidine (pvp) and lactose as fillers.
      Study of pre-compression and post-compression parameters facilitated the
      screening of a formulation with best characteristics that underwent here
      optimization study by response surface methodology (Central Composite Design).
      The optimized tablet was further subjected to scanning electron microscopy to
      reveal its release pattern. The in vitro study revealed that combining of HPMC
      K100M (24.65 MG) with pvp(20 mg)and use of LACTOSE as filler sustained the action
      more than 12 h. The developed sustained release matrix tablet of improved
      efficacy can perform therapeutically better than a conventional tablet. 

PMID- 23960837
TI  - Enhancement of the dissolution of albendazole from pellets using MTR technique.
AB  - Albendazole (ABZ), a broad-spectrum anthelmintic agent, is poorly absorbed after
      oral administration due to its low aqueous solubility. The aim of this study was
      to improve albendazole dissolution rate by formulating avicel pellets loaded with
      10% w/w drug using extrusion/spheronization technique. In addition the wet masses
      were characterized by mix torque rheometry (MTR) prior to pelletization process.
      Different additives (i.e., lactose, Tween 80 and low molecular weight chitosan)
      were formulated with avicel to enhance the dissolution rate of ABZ from the
      produced pellets. Moreover, mix torque rheometer was used to quantitatively
      determine the suitable moisture content in the pastes before the extrusion
      process. The produced pellets were characterized for their ABZ content, particle
      size, particle shape, dissolution profile and thermal behaviors. The maximum
      consistencies (the peak torques) of the wet granules were obtained using 0.667
      1.333 ml/g of water or water containing surfactant. Also, the produced pellets
      have size range from 1036 to 1246 MUm. The calculated drug RDR30 for 10%, 30% and
      50% lactose concentrations were 1.08, 1.08 and 2.03, respectively, while that
      calculated for 10%, 30% and 50% w/w chitosan concentrations were 1.71, 3.62 and
      3.62, respectively. The results revealed also that increasing the weight ratio of
      lactose and chitosan was accompanied by a significant reduction of the peak
      torque magnitude and this was accompanied by an enhanced ABZ dissolution rate. 

PMID- 23960838
TI  - Insulin vials vs. insulin cartridges: Further cost considerations.
AB  - SCOPE: Many studies have provided evidence that favor the use of insulin pens
      over traditional insulin vials due to lower overall costs. The cost of insulin in
      the Royal Medical Services in Jordan is subject to other considerations due to
      the favorable tender prices and the process of dispensing of insulin within the
      Royal Medical Services. OBJECTIVE: To highlight further cost considerations
      associated with the wastage in the use of insulin vials and cartridges in the
      Jordanian Royal Medical Services. METHODS: Two random samples were selected from
      prescriptions dispensed for diabetic patients using insulin in January 2012 from
      the outpatient pharmacy in Al-Hussein Hospital, King Hussein Medical Center,
      Amman, Jordan. First sample was selected from prescriptions of patients using
      vials; second sample was selected from prescriptions of patients using pens and
      cartridges. Average costs for insulin and wastage were calculated per patient
      from the Royal Medical Services perspective. RESULTS: The average direct cost per
      patient using vials was JD 5.197 and for those using cartridges was JD 22.135.
      The average wasted quantity per patient in the first sample was more than ten
      times that of the second sample. The cost of the average wasted quantity per
      patient in the first sample (1.022 JD) was more than the double that in the
      second sample (0.441 JD). CONCLUSION: Although, the direct cost of insulin per
      patient by using vials was lower than cartridges, there was a substantial
      reduction in the cost of wastage by using the cartridges in the Jordanian Royal
      Medical Services outpatients.

PMID- 23960839
TI  - Embryonic signature in breast cancers; Pluripotency roots of cancer stem cells.
AB  - Drug discovery programs for preclinical oncology typically select compounds which
      have a predilection for inducing cytotoxic effects in cancer cell lines and
      subsequently, for inhibiting the growth of the transplanted cancer cells in vivo
      (Winquist et al., 2010). Unfortunately, the cytotoxic effect in vitro and
      inhibition of tumor growth in animal models are not the end story for curing
      cancer in preclinical models. The reason behind that is the exciting of small sub
      type of cells that are relatively resistance to therapy and able to repopulate in
      vivo, called cancer stem cells (CSCs). O leis et al. recently reported that the
      pluripotency gene Sox2 but not Oct4 or Nanog is expressed in early stage of
      breast tumor. Furthermore, the authors demonstrated that Sox2 downregulation,
      inhibited mammosphere formation and delayed tumor formation in xenograft tumor
      initiation models (Leis et al., 2012). In this review, we will shed the light on
      the importance of Sox2 in breast and other tissue tumorigenesis and associated
      aggressiveness. 

PMID- 23960840
TI  - Adenosine and its receptors as therapeutic targets: An overview.
AB  - The main goal of the authors is to present an overview of adenosine and its
      receptors, which are G-protein coupled receptors. The four known adenosine
      receptor subtypes are discussed along with the therapeutic potential indicating
      that these receptors can serve as targets for various dreadful diseases. 

PMID- 23960841
TI  - A study investigating the level of satisfaction with the health services provided
      by the Pharmacist at ENT hospital, Eastern Region Alahsah, Kingdom of Saudi
      Arabia.
AB  - The current study aims to evaluate the patient's level of satisfaction with
      health care services provided by the pharmacist at Aljaber ENT hospital, Eastern
      Region Alahsah, Kingdom of Saudi Arabia. A cross sectional study was planned from
      1st March 2011 until 31st May 2011. A 27 item questionnaire was used, scoring of
      the responses was done to classify the patient satisfaction into sublevels. The
      maximum possible score was 36; those scoring less than twenty were graded as poor
      satisfaction level followed by moderate satisfaction level 21-25, good
      satisfaction level 26-30 and high satisfaction level 31-36. Statistical package
      for social science version 13(r) was used to analyze data, One-way ANOVA and
      independent sample t-test were applied to see the differences in the level of
      satisfaction. Every third patient visiting pharmacy was given a chance to
      participate in this study. A total of N = 991 patients were randomized using the
      pharmacy appointment number. Of whom 657 patients have shown willingness to
      participate in this study. The response rate of this study was 66.30%, most of
      the respondents 383 (58.1%) were male ranging from the age group of 21-40 years
      with a mean age of 32 years SD 9.73. The mean score for all patients was 26.15 SD
      +/-3.4. Among all the demographic variables a significant difference in
      satisfaction level was found among in terms of age (df = 8, F = 8.36, p =
      <0.001(*)), gender (t = -4.089, df = 656, p=<0.001(*)) and race (df = 2, F =
      8.47, p = <0.001. The satisfaction level among Saudi nationals was least in
      comparison to Egyptians and others. In general, it is seen that respondents of
      age 56-60 years were most satisfied with the healthcare services provided by the
      pharmacist. In addition, the satisfaction level was higher among female patients
      in comparison to men. 

PMID- 23960842
TI  - Adverse drug reactions in hospitalized pediatric patients of Saudi Arabian
      University Hospital and impact of pharmacovigilance in reporting ADR.
AB  - OBJECTIVES: Children are more vulnerable to ADRs, and this susceptibility is
      compounded due to hospitalization. There is a lack of local data regarding the
      potential risk of ADRs in hospitalized pediatric patients. Therefore, this study
      is designed to identify the frequent nature, severity of adverse drug reactions,
      drugs implicated and factors influencing ADRs. METHODS: Intensive monitoring
      study of ADRs was done in hospitalized pediatric patients of King Abdulaziz
      University Hospital, Jeddah from January to December 2011, with an analogous
      retrospective study for the preceding year to determine incidence rate,
      demographic aspects, causality appraisal, polypharmacy, body organs/systems
      involved and drugs implicated in ADR. Comparison of the two data was done to
      determine the impact of pharmacovigilance. RESULTS: Incidence rate of ADRs in
      retrospective study was (4.50%) and (8.2%) in prospective study. ADR was more in
      patients who received 5-6 drugs, which was (15.5%) in retrospective study and
      (22.1%) in prospective study. Regarding age, it was the highest in patients of 0
      1 year of age which was (40.7%) in retrospective study and (38.8%) in prospective
      study. Anti-infective agents were the most frequently involved in ADR (40.8%) in
      prospective study and (48.2%) and retrospective study. This study also
      demonstrated that, there was high susceptibility of the skin to the ADR which was
      (37%) in retrospective study and (42.9%) in prospective study. None of the ADRs
      proved to be fatal. CONCLUSION: Well premeditated intensive monitoring approach
      in pharmacovigilance amplifies the ADR detection, which can persuade healthcare
      providers into more drug safety.

PMID- 23960843
TI  - Pharmaceutical policies used by private health insurance companies in Saudi
      Arabia.
AB  - BACKGROUND: Currently, the Council of Cooperative Health Insurance (CCHI) is the
      body responsible for regulating health insurance in the KSA. While the
      cooperative health insurance schedule (i.e., model policy for health insurance)
      is available on the CCHI web site, policies related to pharmaceuticals are
      ambiguous. AIMS: The primary objective of this study was to assess the impact of
      health insurance policies provided by health insurance companies in KSA on access
      to medication and its use. SETTINGS AND DESIGN: This study was descriptive in
      design and used a survey, which was conducted through face-to-face interviews
      with the medical managers of health insurance companies. METHODS AND MATERIAL:
      The survey took place between March and June, 2011. All 25 insurance companies
      accredited by CCHI were eligible to be included in the study. Out of these 25
      companies, three were excluded from this survey as no response was received.
      RESULTS: All the 16 companies responded "Yes" that they had a prior authorization
      policy; however, their reasons varied. Eight (50%) of the companies were
      concerned about the duration of treatment. While 10 (62.5%) did not offer
      additional coverage over the CCHI model policy, the other 6 (37.5%) reported that
      they could reconcile certain conditions. The survey also demonstrated that 10
      insurance companies allowed refilling of medication but with certain limitations.
      Six out of the 10 permitted refilling within a maximum time of three months,
      whereas the other four companies did not have any time-based limits for
      refilling. The other six companies did not allow refilling without prescription.
      CONCLUSIONS: Although this paper was primarily descriptive, the findings revealed
      a substantial scope for improvement in terms of pharmaceutical policy standards
      and regulation in the health insurance companies in KSA. Additionally, the study
      highlighted such areas to augment the overall quality use of medication, over
      prescribing and irrational use of medication. Further research, thus, is
      definitely needed.

PMID- 23960844
TI  - Intervention to reduce the use of unsafe abbreviations in a teaching hospital.
AB  - OBJECTIVES: To determine the effectiveness of a two-phase intervention designed
      to reduce the use of unsafe abbreviations. METHODS: An observational prospective
      study was conducted at the King Khalid University Hospital in Riyadh, Saudi
      Arabia during May-September 2009. A list of unsafe abbreviations was formulated
      based on the recommendations of the Institute for Safe Medication Practices. The
      first 7000 medication orders written at the beginning of each period were
      collected. Phase one of the intervention involved educating health care
      professionals about the dangers of using unsafe abbreviations. In the second
      phase of the intervention, a policy was approved that prohibited the use of
      unsafe abbreviations hospital-wide. Then, another educational campaign targeted
      toward prescribers was organized. Descriptive statistics are used in this paper
      to present the results. RESULTS: At baseline, we identified 1980 medication
      abbreviations used in 7000 medication orders (28.3%). Three months after phase
      one of the intervention, the number of abbreviations found in 7000 medication
      orders had decreased to 1489 (21.3%). Six months later, after phase two of the
      intervention, the number of abbreviations used had decreased to 710 (10%). During
      this phase, the use of all abbreviations had declined relative to the baseline
      and phase one use levels. The decrease in the use of abbreviations was
      statistically significant in all three periods (P < 0.001). CONCLUSION: The
      implementation of a complex intervention program reduced the use of unsafe
      abbreviations by 65%.

PMID- 23960845
TI  - Assessment of antibiotic prescribing at different hospitals and primary health
      care facilities.
AB  - In this study, it was aimed to investigate the utilization of antibiotics at
      various health care facilities. Photocopies of 1250 prescriptions which were
      containing antibiotics and written out in primary health care facilities (PHCFs),
      public hospitals (PHs), private hospitals and university hospitals in 10
      provinces across Turkey, were evaluated by some drug use indicators. The number
      of drugs per prescription was 3.23 +/- 0.92 and it was highest in PHCFs (3.34 +/-
      0.84), (p < 0.05). The cost per prescription was 33.3 $, being highest in PHs
      while being lowest in PHCFs (38.6 $ and 28.2 $ respectively). Antibiotic cost per
      prescription was 16.7 $ and it was also highest and lowest in PHs and PHCFs
      respectively (p < 0.05). The most commonly prescribed group of antibiotics was
      "beta-lactam antibacterials, penicillins" (29.2%) while amoxicillin/clavulanic
      acid was the most commonly prescribed antibiotic (18.1%). Sixty-one percent of
      the antibiotics prescribed for acute infections was generics; among facilities
      being highest in PHCFs (66.5%) and among diagnosis being highest in acute
      pharyngitis. In general, the duration of antibiotic therapy was approximately 7
      days for acute infections. Although much more drugs were prescribed in PHCFs than
      others, it was found to be in an inverse proportion with both the total cost of
      prescriptions and the cost of antibiotics. Broad-spectrum antibiotics, beta
      lactamase combinations in particular, were considered to be more preferable in
      all health care facilities is also notable. These results do serve as a guide to
      achieve the rational use of antibiotics on the basis of health care facilities
      and indications. 

PMID- 23960846
TI  - An approach for lacidipine loaded gastroretentive formulation prepared by
      different methods for gastroparesis in diabetic patients.
AB  - The present work deals with various attempts to prepare a gastroretentive
      formulation of lacidipine for treating gastroparesis. High density sucrose beads
      were modified by coating with certain polymers, but unfortunately sustained
      release could not be achieved. Granules were prepared by wet granulation
      technology using different combinations of polymers and a release of the drug was
      observed. The method failed to release the drug as per desired specifications.
      Polymeric coating followed by wet granulation was thought to be a better process
      to sustain the dissolution rate. The release rate can be modified by the
      incorporation of different polymeric coatings, but the mucoadhesive potential of
      granules was only 4.23% which might be due to its large size and the presence of
      other ingredients. Further, the lacidipine loaded microparticles were prepared by
      different methods such as compression, ionic gelation with TPP, ionic gelation
      with TPP and glutaraldehyde, spray drying and coacervation techniques. The
      formulations were evaluated for average particle size, surface morphology,
      entrapment efficiency, % yield and mucoadhesive potential. The microparticles
      prepared by compression method using HPMC K4M and SCMC as mucoadhesive polymers
      and BaSO4 as high density diluent showed poor bioadhesion (8.3%) and poor release
      characteristics (100% in 120 min). Ionic gelation with tripolyphosphate yielded
      microspheres with poor mechanical strength. In order to improve its mechanical
      strength, TPP ionic gelation was combined with step-wise cross-linking with
      glutaraldehyde. The additional solidification step to improve mechanical strength
      left this procedure tedious, time consuming and cytotoxic. Spray drying method
      gave a very low yield with 46.67% bioadhesion. The method using CaCl2 for
      ionotropic gelation showed the best results with regard to physical
      characteristics (well formed discrete, spherical surface microcapsule), particle
      size (88.57 +/- 0.51), in vitro bioadhesion (67.33%), yield (>85%) and loading
      (>70%). 

PMID- 23960847
TI  - Synthesis and anticancer activity of some fused pyrimidines and related
      heterocycles.
AB  - On account of the reported anticancer of pyrimidine and condensed pyrimidine, a
      new pyrimido [3,2-b]-1,2,4,5-tetrazine 3a , b , 5c , d , 6, 9, pyrimido [3,2-b]
      1,2,4-triazine 10, 11, pyrimido [3,2-b]-1,2,4-triazole 12 and pyrimidine
      derivatives 1,2a , b , 4c , d , 8, 13, 14, 15 and 16 were synthesized through
      different chemical reactions. Structures of all synthesized compounds were
      supported by spectral and elemental analyses. The obtained compounds were
      evaluated for their in vitro antitumor activity against human liver cancer cell
      line (HEPG2). 

PMID- 23960848
TI  - Development and validation of RP-HPLC method for sildenafil citrate in rat plasma
      application to pharmacokinetic studies.
AB  - Sildenafil citrate (SIL) is used in the treatment of erectile dysfunction and
      other chronic disorders. For the pharmacokinetic investigation of SIL we
      developed a simple and sensitive method for the estimation of SIL in rat plasma
      by reverse phase high-performance liquid chromatography (RP-HPLC). The drug
      samples were extracted by liquid-liquid extraction with 300 MUl of acetonitrile
      and 5 ml of diethyl ether. Chromatographic separation was achieved on C18 column
      using methanol:water (85:15 v/v) as mobile phase at a flow rate of 1 ml/min and
      UV detection at 230 nm. The retention time of SIL was found to be 4.0 min having
      a separation time less than 5 min. The developed method was validated for
      accuracy, precision, linearity and recovery. Linearity studies were found to be
      acceptable over the range of 0.1-6 MUg/ml. The method was successfully applied
      for the analysis of rat plasma sample for the application in pharmacokinetic
      study, drug interaction, bioavailability and bioequivalence. 

PMID- 23960849
TI  - A case report from Nepalese community pharmacy on levofloxacin induced severe
      abdominal pain.
AB  - A 46-year-old female patient developed severe abdominal pain shortly after taking
      levofloxacin, 1000 mg for acute bacterial sinusitis. The pain started after
      taking the first dose of levofloxacin and became worse after the second dose. The
      patient was unable to do daily physical activities. The pain resolved upon
      discontinuation of levofloxacin and symptomatic therapy. Other factors that may
      cause abdominal pain were ruled out. This case is of interest as it documents
      severe abdominal pain due to levofloxacin requiring discontinuation of therapy
      and describes its appropriate management. In addition, it highlights the vital
      role that community pharmacists could play in managing adverse drug reactions
      (ADRs) and preventing potential Drug Related Problems (DRPs). 

PMID- 23960850
TI  - Perspective: Lacrimal gland biopsy, is it important?

PMID- 23960851
TI  - Diabetic macular edema.
AB  - A variety of treatment options are available for the treatment of diabetic
      macular edema. They include laser photocoagulation, anti-VEGF drugs, intravitreal
      steroids, and vitrectomy with or without release of vitreoretinal traction. A
      full understanding of the physiological mechanisms of these treatment modalities
      allows sensible combination of treatment options. Retinal photocoagulation has
      repeatedly been shown to improve retinal oxygenation, as does vitrectomy. Oxygen
      naturally reduces VEGF production and thereby decreases leakage of plasma
      proteins from capillaries into the tissue. In addition, vitrectomy allows faster
      clearance of cytokines, such as VEGF, from the retina into the vitreous cavity.
      The VEGF-lowering effect of photocoagulation and vitrectomy can be augmented with
      anti-VEGF drugs and corticosteroids reduce the effect of VEGF on capillary
      permeability. Starling's law explains vasogenic edema, which is controlled by
      osmotic and hydrostatic gradients between vessel and tissue. It explains how VEGF
      induced vascular permeability causes plasma protein to leak into the tissue
      interstitial space, thus decreasing the osmotic pressure gradient between vessel
      and tissue, resulting in water accumulation, i.e. edema. This is reversed by
      reducing VEGF production, which is achieved with laser treatment; or by removing
      VEGF with antibodies or vitrectomy; or by reducing the permeability effect with
      steroids. At the same time, Starling's law takes into account hemodynamic changes
      that affect the hydrostatic gradient. High arterial blood pressure and hypoxic
      vasodilatation increase the hydrostatic pressure in the microcirculation, which
      increases water flux from vessel to tissue and induce edema. Treatment of
      arterial hypertension or reversal of retinal hypoxia with laser reverses this
      pathophysiology and reduces edema. Newton's third law explains, that
      vitreoretinal traction decreases hydrostatic tissue pressure in the retina,
      increases the pressure gradient between vessel and tissue, and stimulates water
      fluxes from vessel into tissue, leading to edema. Release of vitreoretinal
      traction reverses this mechanism and reduces edema. 

PMID- 23960852
TI  - Bimanual microincisional cataract surgery technique and clinical outcome.
AB  - Bimanual microincisional cataract surgery has been introduced recently as a
      technique for cataract surgery and it is gaining interest of many cataract
      surgeons in the world. Over the last few years many changes were made in the
      phacoemulsification machines and the intraocular lenses design which allowed
      bimanual microincisional cataract surgery to be safer and more efficient. The
      purpose of this review is to introduce the technique of bimanual microincisional
      cataract surgery and to review all the prospective randomized studies comparing
      bimanual microincisional cataract surgery and standard phacoemulsification in
      term of safety and efficacy parameters. 

PMID- 23960853
TI  - Uveal melanoma in the Saudi Arabian population: Two decades of management at the
      King Khaled Eye Specialist Hospital.
AB  - OBJECTIVE: To present the experience of King Khaled Eye Specialist Hospital
      (KKESH) with uveal melanoma over the last two decades in a fashion similar to the
      result of the Collaborative Ocular Melanoma Study (COMS). DESIGN: Retrospective,
      non-comparative, interventional, case series. PARTICIPANTS: All patients were
      diagnosed with uveal melanoma at the King Khaled Eye Specialist Hospital (KKESH),
      Riyadh, Saudi Arabia from June 1983 to July 2005 and met the inclusion criteria
      of the COMS. METHODS: A medical record review of clinical history, imaging
      studies, surgical procedures and treatment outcome was performed. RESULTS: Forty
      patients (24 males and 16 females) with uveal melanoma (average age 50 years;
      range 24-77 years) were included in the study; 28 (70%) were of Saudi Arabian
      descent and the remaining 12 (30%) patients were from neighboring Arab countries.
      Decreased vision was the main presenting complaint of 29 (72.5%) patients; the
      duration of this symptom was 3 months or more in 27 (67.5%) patients. The apical
      height of the tumor was 10 mm or more in nine (22.5%) of the affected eyes and
      the largest basal dimension was more than 16 mm in nine (22.5%) of the affected
      eyes. The posterior border of the tumor was 1-2 mm from the optic disc in three
      (7.5%) affected eyes. Primary enucleation was performed for 33 (82.5%) eyes,
      episcleral radiation plaque therapy for six (15%) of the eyes and endo resection
      of the uveal melanoma in one (2.5%) eye. Adjunct external beam radiation therapy
      was performed in two (5%) orbits for extrascleral extension. The
      histopathological diagnosis was available for 34 (84%) eyes in which surgery had
      been performed (33 patients underwent primary enucleation and one patient
      underwent endo resection of the uveal melanoma); 24 (70.6%) eyes had spindle cell
      and the remaining 10 (29.4%) had epithelioid or mixed cell types. Evidence of
      extraocular tumor extension was found in three eyes. The average follow-up was
      33.7 months with a median of 19 months (range 0.5 months to 10 years). Two (5%)
      patients developed metastasis after 2 years and 5 years from the initial
      treatment of large and medium-sized uveal melanomas, respectively. CONCLUSION:
      Individuals of Saudi Arabian ancestry appear to have a low incidence of uveal
      melanoma. Further studies are required to estimate the true incidence of uveal
      melanoma in the larger Arab population. Early detection is essential for
      improving the patient outcomes. Regular communication between the tertiary care
      eye centers and the local ophthalmic care providers is required to enhance the
      understanding about uveal melanoma behavior in Arab population.

PMID- 23960854
TI  - Anticardiolipin antibodies in proliferative diabetic retinopathy: An additional
      risk factor.
AB  - PURPOSE: To report the prevalence of anticardiolipin antibodies in patients with
      proliferative diabetic retinopathy (PDR) having high-risk criteria (HRC).
      METHODS: Diabetic patients having PDR with HRC and diabetics free of retinopathy
      were compared for the presence of anticardiolipin antibodies. RESULTS: Among the
      34 patients, 6 (17.7%) of diabetics having PDR with HRC were positive for
      anticardiolipin antibodies. There was no significant association of aCL
      antibodies with sex or type of diabetes. Using Pearson's correlation test, no
      significant associations of aCL antibodies with duration of diabetes or age of
      patients were found. All patients who were positive for anticardiolipin
      antibodies had PDR with HRC. The difference was statistically significant.
      CONCLUSION: Presence of anticardiolipin antibodies may represent an additional
      risk factor for PDR.

PMID- 23960855
TI  - Smallpox: An eradicated infection with persistent sequels - Case report and a
      brief on smallpox.
AB  - Sequelae of smallpox infection on the ocular surface are still seen, including
      corneal scars adherent leukoma and phthisical globes. This paper will report
      another sequel of smallpox infection causing inadvertent bleb in a 62-year-old
      diabetic female with no history of ocular surgery or trauma in either eye. The
      patient had smallpox infection during her childhood. Her follow up extended from
      May 1997 until August 2007 with a constant eye examinations including controlled
      intraocular pressure, avascular cystic inadvertent bleb, and up drown peaked
      pupil. 

PMID- 23960856
TI  - Capsular phimosis with complete occlusion of the anterior capsular opening after
      intact continuous curvilinear capsulorrhexis.
AB  - Shrinkage and whitening of the anterior capsule opening - capsular contraction
      syndrome - is a well-known complication after continuous curvilinear
      capsulorrhexis. A 72-year-old women underwent continuous curvilinear
      capsulorrhexis, phacoemulsification, and implantation of posterior chamber
      intraocular lens with polymethylmethacrylate haptics. Four months
      postoperatively, the patient reported deterioration in visual acuity that was
      resulted due to complete occlusion of anterior capsular opening by fibrotic
      tissue. The fibrous membrane was excised surgically in capsulorrhexis fashion. 

PMID- 23960857
TI  - Measurement of central corneal thickness in health and disease.

PMID- 23960858
TI  - Comparison of central corneal thickness measurements by Pentacam, noncontact
      specular microscope, and ultrasound pachymetry in normal and post-LASIK eyes.
AB  - PURPOSE: To compare central corneal thickness (CCT) measurements taken with
      Pentacam, noncontact specular microscope (NCSM), and ultrasound pachymetry (US)
      in normal and post-laser in situ keratomileusis (LASIK) eyes and to assess the
      agreement between the three devices. DESIGN: Prospective clinical trial. PATIENTS
      AND METHODS: Central corneal thickness (CCT) was measured in 94 eyes of normal
      volunteer and in 72 eyes of post-LASIK patients. Measurements were made with the
      three devices. RESULTS: In normal eyes, the mean (+/-SD) CCT taken with Pentacam,
      NCSM, and US was 552.6 +/- 36.8 MUm, 511.9 +/- 38.6 MUm, and 533.3 +/- 37.9 MUm,
      respectively. The average values of CCT taken with the three instruments were
      significantly different. In post-LASIK eyes the mean CCT with Pentacam, NCSM, and
      US was 483.02 +/- 6.03 MUm, 450.7 +/- 5.3 MUm, and 469.5 +/- 5.8 MUm,
      respectively. The average values of CCT taken were significantly different for
      Pentacam vs. NCSM (P = 0.046) and Pentacam vs. US (P = 0.02), but not significant
      for NCSM vs. US (P = 0.352). The Bland and Altman method for assessing clinical
      agreement between 3 instruments showed that in normal eyes, the mean values and
      paired differences of the three CCT devices were found to be statistically
      independent. In post-LASIK eyes, there was significant association between the
      difference and the mean of the Pentacam and NCSM, and US and NCSM. CONCLUSION:
      The three devices cannot be used interchangeably in normal and post-LASIK eyes.
      Pentacam tends to give significantly thicker reading than ultrasound pachymetry.

PMID- 23960859
TI  - Comparative study of phacoemulsification-subscleral trabeculectomy versus
      phacoemulsification-deep sclerectomy.
AB  - PURPOSE: To compare the surgical outcomes of phacoemulsification-subscleral
      trabeculectomy versus phacoemulsification-deep sclerectomy with intraoperative
      mitomycin C in open-angle glaucoma. METHODS: The study was conducted on 40
      chronic primary open-angle glaucomatous eyes with senile cataract. They were
      divided into two groups: group I (n = 20): eyes undergoing phacoemulsification
      with subscleral trabeculectomy, and group II (n = 20): eyes undergoing
      phacoemulsification with deep sclerectomy. Intraoperative mitomycin C (0.4 mg/ml
      for 3 min) was applied in both groups. Postoperative intraocular pressure (IOP),
      complications, glaucoma medications, visual outcomes, and the bleb appearance
      were assessed for 12 months. RESULTS: The mean postoperative IOP was
      significantly lower (P < 0.05) in both groups in all time intervals in comparison
      to their preoperative values. The mean postoperative IOP was 14.1 +/- 5.4 mmHg in
      group I, and 14.8 +/- 3.1 mmHg in group II. No major complications were
      encountered in either procedure, but complications such as shallow anterior
      chamber, hypotony, and delayed bleb leaks were common in group I, whereas
      intraoperative perforation of Descemet's membrane occurred in group II. No
      significant difference in visual acuity improvement, visual field changes, and
      surgical success outcome were found between both groups. CONCLUSION: There was no
      significant difference in IOP reduction, surgical complications and visual
      outcomes between subscleral trabeculectomy, or deep sclerectomy with
      intraoperative mitomycin C in combination with phacoemulsification and
      intraocular lens implantations in patients with primary open-angle glaucoma.

PMID- 23960860
TI  - Glial tumors of the retina. The 2009 King Khaled Memorial Lecture.
AB  - Retinal glial tumors and pseudotumors can be classified into astrocytic
      hamartoma, acquired retinal astrocytoma, massive gliosis, and focal nodular
      gliosis. Each has different clinical manifestations. Astrocytic hamartoma is
      usually seen patients who have some manifestations of tuberous sclerosis complex
      (TSC). It can occur as a noncalcified or calcified variety, and often a
      combination of the two, and has fairly typical features with fluorescein
      angiography, ultrasonography, and optical coherence tomography. Although it is
      generally a stationary lesion, an aggressive variant seen in very young children
      with TSC can lead to exudative retinopathy, retinal detachment, and neovascular
      glaucoma. Acquired astrocytoma general occurs in somewhat older individuals who
      do not have TSC. Like the aggressive form of astrocytic hamartoma it can lead to
      exudative retinopathy and exudative retinal detachment. Pseudoneoplastic diffuse
      retinal gliosis can occur as massive glial proliferation in eyes with prior
      trauma, Coats disease, retinal angiomatosis and other conditions and often occurs
      in blind eyes. Pseudoneoplastic focal retinal gliosis is characterized by a very
      superficial, white, noncalcified lesion in otherwise normal eye in somewhat older
      individuals. Recognition of these glial lesions is important because they can
      resemble malignant tumors and have different clinical courses and complications. 

PMID- 23960862
TI  - Periocular hidradenoma papilliferum.
AB  - Hidradenoma is a benign adnexal neoplasm originating from the apocrine sweat
      gland, and is almost exclusively detectable in the skin of the anogenital area of
      middle-aged white females after puberty. Ectopic hidradenoma papilliferum, which
      involves the skin away from the anogenital region, is exceedingly rare, and can
      also affect males. We report a female patient with a lesion (dating back to
      childhood) close to the medial end of the left eyebrow and overriding the
      anterior medial part of superior orbital rim. The lesion was completely excised
      and had not reoccurred during over four years of follow-up. 

PMID- 23960861
TI  - Deep anterior lamellar Keratoplasty.
AB  - Keratoconus is a disease causing increased steepening of the cornea resulted in
      irregular astigmatism. Treatment options are Glasses, Hard contact lenses, Cross
      linking, Intracorneal Segments insertion, Refractive surgery (Gilda et al.,
      2008), or Keratoplasty. Lamellar Keratoplasty (LKP) can be a better choice to
      manage cases of moderate and some cases of severe Keratoconus without deep
      scarring and severe thinning, also in cases of corneal scarring not involving the
      deeper layers of the cornea. LKP is a corneal graft technique consisting of
      transplantation of partial-thickness donor tissue, devoid of endothelium,
      Descemet membrane (DM), and rear stroma into a recipient healthy stromal bed
      after dissection of pathologic anterior stroma. However, deep lamellar
      Keratoplasty (DLKP) is a surgical method that completely removes pathologic
      corneal stroma tissue down to the DM, followed by transplantation of donor cornea
      without endothelium over the host bed. DLKP has a number of advantages over
      penetrating Keratoplasty (PKP). Because it does not violate the intraocular
      structures of the eye, it diminishes or eliminates the chance of postoperative
      glaucoma, cataract formation, retinal detachment, cystoids macular edema,
      expulsive choroidal hemorrhage and epithelial ingrowths. Furthermore, this
      procedure avoids the replacement of host endothelium with donor endothelium and
      thus precludes endothelial graft rejection, with comparable visual outcomes and
      low rate of chronic endothelial cell loss compared to PKP. 

PMID- 23960863
TI  - Bilateral acute angle closure glaucoma after hyperopic LASIK correction.
AB  - Acute angle closure glaucoma is unexpected complication following laser in situ
      keratomileusis (LASIK). We are reporting a 49-years-old lady that was presented
      to the emergency department with acute glaucoma in both eyes soon after LASIK
      correction. Diagnosis was made on detailed clinical history and examination, slit
      lamp examination, intraocular pressure measurement and gonioscopy. Laser
      iridotomy in both eyes succeeded in controlling the attack and normalizing the
      intraocular pressure (IOP) more than 6 months of follow-up. Prophylactic laser
      iridotomy is essential for narrow angle patients before LASIK surgery if
      refractive laser surgery is indicated. 

PMID- 23960864
TI  - Eyelid hook injury - A preventable domestic injury.
AB  - The aim of this report is to describe the presentation and management of eyelid
      injury resulting from the hook of a rubber string. A seven-year-old boy presented
      with pain of the right upper eyelid. A rubber string with metal hook ends,
      snatched his right eye from below. The hook pierced through his upper eyelid from
      the conjunctival surface and remained in situ. However, there was no globe
      laceration noted. Removal was performed by reverse-tracking of the hook through
      the wound. The wound was stitched with 6'0 Vicryl sutures. Healing was excellent
      with minimal scarring. 

PMID- 23960865
TI  - Ophthalmic Pathology: The history of a growing profession.

PMID- 23960866
TI  - Laser in situ keratomileusis for treated myopic anisometropic amblyopia in
      children.
AB  - PURPOSE: To evaluate the effects of laser in situ keratomileusis (LASIK) in
      decreasing myopic anisometropia in children with spectacles or contact lens
      intolerance and its validity in facilitating treatment of resultant myopic
      anisometropic amblyopia. PATIENTS AND METHODS: LASIK was performed in 18 eyes of
      18 children having myopic anisometropic amblyopia not successfully treated with
      the standard amblyopia treatment for 6 months. Children were followed up at 1
      week, 1, 2, 6, 12, 18 and 24 months. Postoperative amblyopia therapy was
      continued with occlusion of the dominant eye for 6 h daily for the first 3 months
      and then for 4 h per day as long as possible. RESULTS: The mean spherical
      equivalent refraction in the operated eye had reduced significantly from -9.08 +/
      1.86D preoperatively to -0.97 +/- 1.16D at 2 years postoperatively. The mean
      spherical equivalent in the non-operated fellow eye was -1.0 +/- 1.15D
      preoperatively and -2.50 +/- 1.15D at 2 years. The mean spherical equivalent
      myopic anisometropia was -7.75 +/- 2.25D preoperatively and -0.50 +/- 0.31D at 2
      years, representing a 93.5% reduction in myopic anisometropia. The mean
      regression value was -2.28 +/- 1.62D, however, 18 eyes (72%) were within 3.0D of
      the fellow eye. The mean BCVA was significantly improved from 0.72 +/- 0.13
      preoperatively to 0.47 +/- 0.17 by 2 years after LASIK with amblyopia treatment.
      CONCLUSION: LASIK is a safe and effective alternative method for correcting
      myopic anisometropic amblyopia, especially in children with spectacles or contact
      lens intolerance, with more better visual acuity and binocular vision.

PMID- 23960867
TI  - Controlled Cyclophotocoagulation with diode laser in refractory glaucoma and long
      term follow up at King Abdulaziz University Hospital, Riyadh.
AB  - PURPOSE: To evaluate the clinical efficacy and safety of controlled contact
      transscleral diode laser Cyclophotocoagulation (COCO) procedure in reducing the
      Intraocular Pressure (IOP) among patients with refractory glaucoma. METHODS:
      Thirty two patients (35 eyes) with refractory glaucoma in prospective clinical
      studies were treated with trans-sclera diode laser in a controlled manner. The
      energy power used was 5 W in adults and 3 W in children, exposure time was 0.5 s,
      a total of 16 shots were applied over ciliary body and four shots in each
      quadrant. Pre and postoperative IOP were measured at different postoperative
      visits. Snellen visual acuity, the number of anti-glaucoma medications and
      associated complications were also recorded. Student T test was used to compare
      the pre and post intervention IOPs, while Wilcoxon Signed Ranks test was used, to
      detect significance change in medication dependency. RESULTS: The mean (SD)
      follow up time was 80.2(+/-9.6) months, range (36-84) m, where the mean IOP was
      significantly reduced from 35.1 mm Hg (+/-10.7) before intervention to 18.8 mm Hg
      (+/-7.3) after intervention, in the final visit (P < 0.0001). Complete success
      was achieved in seven eyes (20%), 22 eyes (62.8%) showed qualified successes and
      complete failure was reported in six eyes (17.1%). The overall success rate was
      82.8% (95% CI: 70.4-95.3). Visual acuity improved in three eyes (8.5%), no change
      took place in 27 eyes (77.1%) and decreased in five eyes (14.2%). The number of
      anti-glaucoma medications has significantly changed between pre and post
      intervention (P < 0.0001). No cases of hypotony, phthisis bulbi or sympathetic
      ophthalmia were reported. CONCLUSION: Controlled COCO is a simple procedure, safe
      with minimal complications and fewer side effects.

PMID- 23960868
TI  - Eradicating blinding trachoma: What is working?
AB  - Trachoma remains the leading cause of preventable corneal blindness in developing
      countries. The disease is contracted in early childhood by repeated infection of
      the ocular surface by C. trachomatis. Initial clinical manifestation is a
      follicular conjunctivitis which if not treated on timely basis, may lead to
      conjunctival and eyelid scarring that may eventually result in corneal scarring
      and loss of vision. Over the past two decades, a remarkable reduction in the
      prevalence of active trachoma has occurred due to the World Health Organization's
      (WHOs) program GET 2020 for the elimination of trachoma with adoption of the SAFE
      strategy incorporating Surgery, Antibiotic treatment, Facial cleanliness and
      Environmental hygiene. However, patients who already had infection at young age
      may present with adnexal-related complications of trachomatous scarring that may
      cause corneal scarring and visual loss. These patients may present with evidence
      of trichiasis/entropion as well as eyelid retraction. Lacrimal complications may
      include nasolacrimal-duct obstruction, dacryocystitis and canaliculitis requiring
      intervention. In addition to the increased risk for corneal scarring,
      trichiasis/entropion may further increase the risks for microbial keratitis in
      patients who may have unrecognized dacryocystitis and canaliculitis. Female
      patients may have more trachomtous-related complications and may present at an
      early age. Available evidence indicates that SAFE strategy may be effective and
      on the right track towards achieving GET 2020 goal for the eradication of
      trachoma. 

PMID- 23960869
TI  - Malignant fibrous histiocytoma in a patient with history of treated
      retinoblastoma.
AB  - Retinoblastoma is one of the most important childhood tumors with genetic
      implications and necessity for family counseling and long term follow up. We are
      presenting a 22 year-old Saudi male with history of bilateral retinoblastoma, who
      was initially treated by enucleation of his left eye. The histopathology showed a
      moderately differentiated tumor with vitreous seeding and he received
      chemotherapy in addition to radiotherapy to his right eye. He presented 20 years
      later with a right orbital tumor, frozen globe and proptosis. The excisional
      biopsy of his orbital mass revealed a spindle cell sarcoma with features of
      malignant fibrous histiocytoma. His clinical and radiological findings are
      presented together with the histopathologic features of his orbital tumor and
      brief review of secondary tumors in retinoblastoma patients. 

PMID- 23960870
TI  - Subconjunctival epithelial inclusion cyst complicating strabismus surgery: Early
      excision is better.
AB  - Epithelial inclusion cysts can occur following otherwise-uncomplicated strabismus
      surgery. Because of their tendency to grow posteriorly into the orbit, they
      should be monitored closely or treated when relatively small. We report and
      discuss an illustrative case. 

PMID- 23960871
TI  - Rare presentation of definitive ocular tuberculosis in an immunocompetent young
      patient.
AB  - Ocular tuberculosis is not uncommon ocular presentation in our community
      nowadays. Rare presentations described mainly in the immunocompromised patients.
      The diagnosis of ocular TB is presumed in the vast majority of the cases of the
      intraocular TB. We are presenting a very rare presentation of definitive
      intraocular TB in a healthy 24-year-old male. 

PMID- 23960872
TI  - Orbital fractures: Timing of surgical repair.

PMID- 23960873
TI  - Three-dimensional characterization of epiretinal membrane using spectral domain
      optical coherence tomography.
AB  - PURPOSE: To describe epiretinal membrane (ERM) features using spectral domain
      optical coherence tomography "SD OCT" and to delineate the three-dimensional (3D)
      relationship in eyes with epiretinal membrane. METHODS: Fifty-two eyes of 44
      patients with ERM were classified into two groups: idiopathic ERM and secondary
      ERM. Posterior vitreous face was evaluated. Pattern of ERM attachment was divided
      into: focal and global. A 3D SD OCT system (5 MUm resolution) was used for
      scanning. Surface maps were used to study retinal topography. RESULTS: Surface
      maps revealed manner and direction of epiretinal traction, pattern of attachment
      and blood vessel involvement. In 55.8% of eyes the membrane was globally adherent
      to the retina. There was a significant association (p = 0.02%) between pattern of
      membrane attachment and etiological classification of eyes. Posterior vitreous
      detachment (PVD) was associated with both groups, but no significant difference
      in between. CONCLUSION: SPECTRAL DOMAIN OCT ALLOWED BETTER CHARACTERIZATION OF
      ERM INCLUDING: visualization, extension, cleavage plane and zones with free
      edges. Surface maps revealed the topography of ERM and retina pathology.
      Idiopathic ERM are significantly associated with global pattern. PVD plays an
      important role in the pathogenesis of primary as well as secondary ERM.

PMID- 23960874
TI  - Prevalence of refractive errors among pre-school children at King Abdulaziz
      Medical City, Riyadh, Saudi Arabia.
AB  - BACKGROUND: Vision disorders are the fourth most common disability of children
      and the leading cause of handicapping conditions in childhood. The present study
      was undertaken to identify the prevalence and pattern of refractive errors among
      the school-entrant children at King Abdul Aziz Medical City (KAMC), Riyadh city -
      Kingdom of Saudi Arabia. METHODS: The study population consisted of all the
      school-entrants (n = 1319), who attended the obligatory health examination for
      kindergarten and primary school entry during the period from March 2008 until
      October 2008. Every child was subjected to a 10 min - visual acuity test (VAT)
      and autorefractive test applied by qualified optometrist. Children with a visual
      acuity of 20/28 or worse in one or both eyes, or with eye disorder (strabismus,
      nystagmus, ptosis and others) or abnormal ocular movement, were referred for a 45
      min complete ophthalmic examination, which consists of: (1) Distance visual
      acuity (V/A), (2) cover - uncover test, and (3) non-cycloplpegic retinoscopy.
      Refractive error cut-off point was defined according to their spherical
      equivalent refractive error (SERE). RESULTS: Out of the 1319 children, 60
      children were diagnosed as having one or more refractive error, with an over-all
      prevalence of 4.5% (4.2% in boys and 4.9% in girls) with no sex difference.
      Prevalence of different refractive errors were as follows; Myopia (2.5%,
      95%CI1.7:3.3%), hyperopia (2.1%, 95%CI 1.3:2.9%), astigmatism (2.5%, 95%CI
      1.7:3.3%), amblyopia (0.5%, 95%CI 0.1:0.9%) and strabismus (0.5%, 95% CI
      0.1:0.9%). CONCLUSION: Our results raise the need for school-based program that
      provides prescription glasses when needed to students at no cost, through
      government and non-governmental collaborative fund. However, there is a need for
      further studies to evaluate the cultural beliefs towards the use of spectacles in
      Saudi communities.

PMID- 23960875
TI  - Orbital Fracture: Significance of lateral wall.
AB  - The lateral orbital wall is the strongest among other orbital walls. However, it
      is commonly fractured in the setting of severe facial trauma. The fracture
      usually occurs at the sphenozygomatic suture line. In general, patients with
      lateral wall fractures are commonly young male who may present with mid facial
      swelling and some degree of deformity. In some cases, lateral orbital wall
      fracture may be associated with visual loss or change in mental status due to
      associated intracranial injury. Imaging studies with computed tomography is
      important in the proper diagnosis and planning of the surgical intervention.
      Management of intracranial or eye injuries should be undertaken on emergent
      basis. Thereafter, significantly displaced lateral wall fractures need to be
      repaired on timely basis. Proper realignment of the plane of the lateral orbital
      wall at the sphenozygomatic suture along with the other complex articulations of
      the zygomatic bone is necessary for proper functional and aesthetic outcome. 

PMID- 23960876
TI  - Orbital alveolar soft part sarcoma: Histopathologic report of two cases.
AB  - Alveolar soft part sarcoma is considered as a distinct histopathological entity
      with rare cases reported from the orbit area. Two cases of alveolar soft part
      sarcomas occurring in the orbit of two patients along with their histopathologic
      findings are reported herewith. In both cases, the patients presented with eyelid
      swelling and proptosis. The diagnosis was made by incisional biopsies and
      histopathology. The literature is reviewed regarding occurrence of this tumor,
      its diagnosis and management. 

PMID- 23960877
TI  - Intravitreal bevacizumab for posterior capsule neovascularization.
AB  - We report a case of rapid regression of extensive posterior capsule
      neovascularization in a 67-year-old diabetic male patient, who developed
      posterior capsule opacity with neovascularization one year post cataract surgery,
      after a single injection of intravitreal bevacizumab (Avastin) followed by
      neodymium:YAG capsulotomy. Rapid regression of the posterior capsule
      neovascularization, and visual improvement was observed 9 days after the
      intervention. Posterior capsulotomy was performed successfully without bleeding.
      Prior to posterior capsulotomy, intravitreal bevacizumab can result in rapid and
      dramatic regression of posterior capsule neovascularization. 

PMID- 23960878
TI  - Image guidance surgery - Is it useful to the orbital surgeon?

PMID- 23960879
TI  - Role of Avastin in management of central serous chorioretinopathy.
AB  - PURPOSE: To evaluate the short-term safety and efficacy of intravitreal
      bevacizumab for the treatment of intraretinal or subretinal fluid accumulation
      secondary to central serous chorioretinopathy (CSC). DESIGN: Prospective
      interventional series non-comparative study. SETTING: Department of
      Ophthalmology, Al-Minya University Faculty of Medicine, Egypt. METHODS: The study
      included 20 eyes of 20 patients with central serous chorioretinopathy (CSC), Out
      of them 10 eyes with acute CSC (group I), 6 eyes with chronic CSC (defined as
      symptoms present for longer than 6 months) and four eyes with recurrent (defined
      as more than one episode of the disease) chronic and recurrent cases are
      considered in one group (group II), all patients were injected with intravitreal
      Avastin (IVA) 1.25 mg (0.05 mL) of commercially available bevacizumab [Avastin;
      Genentech, Inc., San Francisco, CA] as a primary treatment. At baseline and
      follow up visits patients had best corrected visual acuity (BCVA), IOP
      assessment, dilated fundus examination, fundus photography, fluorescein
      angiography (FA) and optical coherence tomography (OCT) imaging is used for
      measurement of central retinal thickness (CRT). Main outcome measures were the
      resolution of neurosensory detachment, improvement in visual symptoms and visual
      acuity, and resolution of leakage in FA. Secondary outcome and measures were the
      need for re-injection and the adverse effects. The mean number of injections was
      2 (range 1-3 injections) 6-8 weeks intervals and follow up for 6 months (range 5
      7 months). All finding at baseline and each follow up visit were reported and
      compared. RESULTS: The mean age of all patients was 40.3 years +/- 6.5 (range 25
      50 years), 15 males and five females patients. In acute CSC group, the mean
      baseline BCVA was 20/60 (log MAR 0.48) and improved to 20/30 (log MAR 0.18) with
      statistically significance difference change (P < 0.003) and in (chronic and
      recurrent group), the mean baseline VA was 20/80 (log MAR 0.60) and improved to
      20/40 (log MAR 0.30) with statistically significance difference change (P <
      0.002). The mean baseline CRT for all patients was 486 +/- 86 MUm (range, 386
      580), decreased to 316 +/- 56 MUm (range, 276-368) after 1 months with
      statistically significance difference change (P < 0.02) and to 272 +/- 52 MUm
      (range 220-338) at last follow up with statistically significance difference
      change from the baseline (P < 0.001). CONCLUSIONS: Intravitreal Avastin (IVA)
      injection was associated with visual improvement and reduced neurosensory
      detachment without adverse events in patients with CSC. Although these results
      are promising, further randomized controlled studies would be helpful to
      understand this therapy for patients with CSC.

PMID- 23960880
TI  - Intra-ocular lens power calculation in patients with high axial myopia before
      cataract surgery.
AB  - PURPOSE: To evaluate the accuracy of different formulas used for IOL power
      calculation in patients with high axial myopia undergoing cataract surgery.
      METHODS: A prospective clinical study was carried out on 53 eyes of 51 patients
      with an axial length from 25.5 to 31.4 mm including 21 males (41.2%) and 30
      females (58.8%). Calculation of the IOL power to be implanted was done by three
      available IOL power formulas; Haigis formula, SRK/T formula, and Holladay I
      formula. The mean error (ME) was calculated from the difference between the
      formula predicted refractive error and the actual post operative refractive
      error. RESULTS: There was no statistically significant difference between the
      mean error of the three formulas used in the overall performance or in the axial
      length subcategories. SRK/T formula caused the smallest mean error, (+0.17 D).
      Haigis formula showed a higher ME (+0.21 D) and Holladay formula caused a myopic
      postoperative refractive error (-0.20 D). CONCLUSION: The calculation of IOL
      power in patients with high axial myopia using the third or the fourth generation
      formulas help in improvement of the accuracy of the calculation and decreasing
      the post operative refractive error. SRK/T formula showed the lowest mean error,
      however, there was not statistically significant difference between the three
      formulas used, neither in the overall performance, nor in axial length
      subcategories.

PMID- 23960881
TI  - Evaluation of the role of timolol 0.1% gel in myopic regression after laser in
      situ keratomileusis.
AB  - PURPOSE: To evaluate the efficacy of the concomitant administration of
      antiglaucoma medications namely timolol 0.1% gel in cases with myopic regression
      after myopic laser in situ keratomileusis (LASIK). DESIGN: Prospective
      observational clinical trial. SUBJECTS AND METHODS: Ninty five eyes of 75
      patients were included in this study prospectively. The mean myopic regression
      was -1.29 +/- 0.83 diopters (range -0.5 to -4.62) after myopic LASIK. The eyes
      were divided into two groups: 50 eyes administrated timolol 0.1% gel once daily
      for 12 months (treated group), and 45 eyes were age matched (control group). We
      assessed the amounts of myopic regression in terms of changes in the refraction
      (spherical equivalent and astigmatism), intraocular pressure (IOP), pachymetry
      and the refractive power of the cornea measurements for all participants.
      RESULTS: The refractive error and visual acuity were similar between the two
      groups at baseline. The treated group had an improvement in spherical equivalent
      significantly from -1.29 +/- 0.83 to -0.94 +/- 1.07 diopters (P = 0.012).
      Astigmatism was changed from -0.94 +/- 0.53 to -0.86 +/- 0.60 diopters but this
      change was not statistically significant (P = 0.20). The IOP was decreased
      significantly from 12.6 +/- 1.9 to 9.0 +/- 1.1 mm Hg (P < 0.001). Central corneal
      thickness was changed from 425.6 +/- 19.86 to 429 +/- 18.1 MUm but not
      statistically significant (P = 0.56). The central corneal power decreased
      significantly from 37.2 +/- 1.8 to 36.4 +/- 1.3 diopters (P < 0.05). CONCLUSION:
      Timolol 0.1% gel was effective for reduction and improvement of myopic regression
      especially the spherical errors after myopic LASIK.

PMID- 23960882
TI  - Early Avastin management in acute retinal vein occlusion.
AB  - PURPOSE: To evaluate the safety, functional and anatomical effects of
      intravitreal Avastin (bevacizumab) in treatment of recent retinal venous
      occlusion. DESIGN: Prospective interventional series non-comparative study.
      SETTING: Department of Ophthalmology, Faculty of Medicine, El-Minia University,
      Egypt. METHODS: The study included 30 eyes of 30 patients with recent retinal
      venous occlusion of less than 3 months duration 12 eyes (40%) of patients with
      central retinal vein occlusion (CRVO) and 18 eyes (60%) with branch retinal vein
      occlusion (BRVO) were injected with intravitreal bevacizumab 1.25 mg (0.05 ml) of
      commercially available bevacizumab [Avastin; Genentech, Inc., San Francisco, CA]
      at a concentration of 25 mg/ml as a primary treatment. The mean number of
      injections was 2.7 (range, 1-6 injections) 6-8 weeks intervals and follow-up for
      12 months (range, 9-13 months). Patients underwent visual acuity testing (VA) as
      functional assessment. Anatomically, optical coherence tomography (OCT) is used
      for measurement of central retinal thickness (CRT) to detect macular edema (ME),
      fundus photography and fluorescein angiography (FA) to detect venous tortuosity,
      optic disc edema and surface wrinkling rather than ME. All finding at baseline
      and each follow-up visit were reported. RESULTS: The mean age of all patients was
      65.3 years +/- 8.5 (range, 55-82 years), 20 males and 10 females patients. The
      mean baseline VA was 20/240 (log MAR 1.08 +/- 0.52) and improved to 20/60 (log
      MAR 0.48 +/- 0.32) with statistically significance difference change (P < 0.001).
      The mean baseline CRT was 455 MUm +/- 126 (range, 386-510), decreased to 356 MUm
      +/- 118 (range, 296-416) after 1 month with statistically significance difference
      change (P < 0.02) and to 402 MUm +/- 170 (range, 338-468) after 6 months (P <
      0.067) and to 250 MUm +/- 48 (range, 200-298) at last follow-up with
      statistically significance difference change from the baseline (P < 0.001). There
      were great proportional decrease in venous tortuosity, optic disc edema and
      surface wrinkling after 1 month of injection. Neither systemic nor intraocular
      adverse events were reported. CONCLUSIONS: Intravitreal Avastin (IVA) is safe
      well tolerated, effectively improve VA, fundus picture and stabilize anterior
      segment neo-vascular activity in patients with recent retinal venous occlusion.

PMID- 23960883
TI  - Completing phaco following anterior capsular tear.
AB  - A primary tear-out of the capsulorrhexis or a later anterior capsule tear occurs
      in less than 1% of phacoemulsification procedures (Marques et al., 2006). It is a
      relatively uncommon complication but a hazardous and important one, although
      comparatively little has been published on its management. With the nucleus still
      in the bag at this stage, the surgeon is faced with the sizeable challenge of
      completing surgery without propagating a wrap-around tear to the posterior
      capsule. These are perilous conditions to face, but by using the right techniques
      the surgeon can still prevail. There is a clear set of principles that are based
      on self-knowledge of the surgeon's own skills and experience, combined with their
      understanding of how to control the forces acting on the tear and the tolerances
      of the capsular bag to surgical manipulation. Applying these principles in
      practice has enabled the development of a range of techniques now available to
      safely remove the nucleus under these challenging conditions. However, by far the
      most important principle of all is that if in doubt, not to proceed. 

PMID- 23960884
TI  - Primary orbital ganglioneuroma in a 2-year-old healthy boy.
AB  - A 2-year-old healthy child presented with progressive unilateral proptosis.
      COMPLETE WORK UP INCLUDING: general examination, detailed ophthalmic evaluation
      and radiological imaging were done. He underwent orbital exploration via anterior
      orbitotomy incision and debulking of the tumor was done. The histopathological
      examination confirmed the diagnosis of orbital ganglioneuroma. Ganglioneuroma is
      an unusual benign tumor of neuroplastic origin with extremely rare orbital
      involvement with only one prior reported case in a youth. The tumor is slow
      growing and non-metastasizing. Biopsy is necessary to differentiate it from the
      malignant neuroblastoma and excision is usually curative.

PMID- 23960885
TI  - Long-term corneal complication of retained anterior chamber-angle foreign body.
AB  - A 33-year-old patient referred to the cornea and anterior segment department to
      evaluate inferior corneal edema related to a retained intraocular foreign body
      (IOFB) in the anterior chamber-angle. The foreign body, which was a single piece
      of glass caused by an exploded light bulb twenty years back, was surgically
      removed; edema resolved and vision improved to 20/30. In the presence of an
      anterior chamber IOFB; long-term adverse effects should be considered. We would
      advise removal of the FB regardless of the inertness and location facts, as long
      as the risk and benefits of the surgical intervention are carefully evaluated. 

PMID- 23960886
TI  - Saudi genetic ophthalmology research: The local and global impact.

PMID- 23960887
TI  - Amyloid corneal deposition in corneal buttons of congenital hereditary
      endothelial dystrophy (CHED) - A clinical and histopathological case series.
AB  - PURPOSE: To determine the frequency, pathology and clinical relevance of amyloid
      deposited in corneas of CHED. METHODS: Clinical and histopathological case
      series. RESULTS: Amyloid subepithelial deposition was found in 5 (6.6%) corneal
      buttons of 75 patients with histopathologically confirmed CHED diagnosis.
      Clinical findings included history of parental consanguinity, poor vision
      (ranging from counting fingers from one foot to 3/200), corneal edema, and
      central whitish subepithelial corneal nodules in all the five cases and positive
      family history in 4 of 5 cases. The patients underwent PKP at a mean age of 15
      years (range 3-22 years). Histological findings included attenuated endothelium
      (6/6) thickened Descemet's membrane (6/6), stromal edema (2/6), and subepithelial
      amyloid deposits (6/6). All patients improved from vision point of view. To date,
      no recurrence of the amyloid has been seen in the grafts. CONCLUSION: Considering
      the consanguinity, family history, early onset, and bilaterality, this study
      supports our hypothesis that the amyloid is primary in nature in our patients and
      indicates a new subtype of autosomal recessive CHED that require further chemical
      and genetic analysis. This subtype has the same prognosis for PKP as all CHED
      patients, if not better.

PMID- 23960888
TI  - RB1 gene mutations in retinoblastoma and its clinical correlation.
AB  - PURPOSE: To find correlation between the type of mutations observed and the
      severity of the disease using multiple techniques like polymerase chain reactions
      (PCR), quantitative multiplex PCR, sequencing and RNA analysis. METHODS:
      Prospective, observational study. Patients who had been screened for mutations in
      the RB1 gene were included in the study. Patient details including demographic
      data; age and sex, laterality, international classification of intraocular
      retinoblastoma (ICIOR) staging, modality of management, histopathology high risk
      factors if the eyes were enucleated and metastasis rate were assessed. RESULTS:
      Seventy four patients were studied. Fifty three patients had bilateral and 21
      unilateral disease. Complete genetic data was analyzed for 74 patients and
      complete clinical correlation was established for all the 49 patients with
      mutations. Of the total mutations identified, 11/49 (22.4%) of patients had large
      deletions, 12/49 (24.5%) had small deletions or insertions, 14/49 (28.6%) had
      nonsense mutations, 7/49 (14.3%) had splice mutations and 5/49 (10.2%) of
      patients had missense mutations. Four cases were familial. Group E ICIOR stage at
      presentation was noted in 40% of patients with large deletions, 33% with small
      deletions whereas 38.5% with splice mutations and 44.4% of patients with missense
      mutations presented with Group B ICIOR. Twenty five percentages of eyes with
      large deletions had high risk features on histopathology and one patient among
      these developed metastasis. CONCLUSION: Current laboratory testing of RB1
      mutations may be feasible in determining the severity of the disease and patient
      counseling. The study provides a starting point for looking at correlations.

PMID- 23960889
TI  - Multifocal electroretinogram in retinal vein occlusion.
AB  - PURPOSE: To determine the effects of retinal vein occlusion (RVO) on multifocal
      electroretinogram (MF-ERG) parameters, to correlate MF-ERG and standard
      electroretinogram (ERG) and to correlate MF-ERG with findings of optical
      coherence tomography (OCT) in cases of RVO. METHODS: Both eyes of 50 patients
      with RVO and 50 eyes of 25 normal subjects were examined using MF-ERG, standard
      ERG, fluorescein angiography and OCT. The latency in millisecond (ms) and
      response density in nanovolt (nv/degenerations) were measured for each of four
      quadrant areas and central area. OCT was used to measure the foveal retinal
      thickness. Fluorescein angiography was used to measure retinal ischemia. RESULTS:
      Central retinal vein occlusion (CRVO) markedly affected all parameters of MF-ERG.
      In pathological quadrants in branch retinal vein occlusion, the response
      densities of MF-ERG were decreased and latencies of p-wave were prolonged. The MF
      ERG responses obtained from eyes with RVO were significantly different (P > 0.05)
      from derived from the fellow eyes. The amplitude of MF-ERG were abnormal in 40
      eyes and implicit times were delayed in 48 eyes compared with normal subjects.
      While 30 Hz flicker implicit were abnormal in only 24 eyes with RVO. Implicit
      times were prolonged in eyes with macular ischemia than in eyes without ischemia.
      There were significant correlation between foveal retinal thickness measured by
      OCT and P response density MF-ERG in cases of retinal vein occlusion. CONCLUSION:
      MF-ERG is more susceptible than standard ERG to eye changes of RVO due to the
      multiple frequencies of stimulation used to record MF-ERG response. MF-ERG could
      be sensitive indicator of underlying disease affecting the retinal in eyes with
      RVO. MF-ERG is useful for detecting local retinal dysfunction in patients with
      RVO and sensitive to morphological changes and functional disorders induced by
      RVO.

PMID- 23960890
TI  - Pretreatment clinical variables associated with the response to intravitreal
      bevacizumab (Avastin) injection in patients with persistent diabetic macular
      edema.
AB  - BACKGROUND: The purpose of the study is to determine whether the pre-treatment
      clinical systemic variables and optical coherence tomography (OCT) findings are
      associated with the subsequent response to the intravitreal bevacizumab (IVB) in
      eyes with persistent diabetic macular edema (DME). DESIGN: Prospective,
      interventional non-comparative case series study. METHODS: 38 Patients (45 eyes)
      with refractory diabetic macular edema; 16 females, 22 males with a mean aged
      57.5 year. All patients had persistent DME not responded to other forms of
      treatments. Complete eye examination; best corrected visual acuity (BCVA)
      (represented as LOGMAR for adequate statistical analysis), slit-lamp exam,
      intraocular pressure measurement, stereoscopic biomicroscopy of the macula, and
      morphologic patterns of diabetic macular edema demonstrated by OCT. All patients
      had intravitreal injection of 0.05 mL = 1.25 mg bevacizumab (Avastin; Genentech,
      Inc., San Francisco, CA), and were followed up for 3 months. The pre and post
      injection follow-up data were analyzed by Student-t test and Mann-Whitney test
      for two main outcome measures; visual acuity (LOGMAR) and central foveal
      thickness (CFT) changes over a period of three months, and the data included
      demographic factors, type, duration and the control of diabetes mellitus
      (HbA1C%), grade of diabetic retinopathy, renal function (serum creatinine level),
      serum cholesterol, blood pressure control and previous treatment by focal laser
      and/or intravitreal triamcinolone injection. RESULTS: The LOGMAR and central
      foveal thickness (CRT) improved in 30/45 eyes (67%) and 32/45 eyes (72%),
      respectively during a mean follow-up time of three months. The mean LOGMAR visual
      acuities were 0.64 (SD +/- 0.34), 0.61 (SD +/- 0.31) and 0.60 (SD +/- 0.32) at
      pre-injection, at 1 month post-injection and at 3 months post-injection,
      respectively; but this mean increase in vision was statistically not significant
      (P value = 0.099). The mean foveal thicknesses were 444.95 MUm (SD +/- 127.36),
      394.95 MUm (SD +/- 138.03) and 378.32 MUm (SD +/- 112.01) at pre-injection, 1
      month post-injection and 3 months post-injection, respectively, this decrease in
      the foveal thickness was statistically significant (P value <0.001). The pre and
      post-injections values of the variables for diabetic duration, diabetic control
      (HbA1c) and OCT pattern of macular edema showed significant statistical
      correlations (P < 0.05) with LOGMAR only, however the values of the variables for
      serum creatinine and cholesterol show statistical correlation (P < 0.05) with
      both LOGMAR and CFT. CONCLUSIONS: Chronicity and inadequate control of diabetes
      mellitus, nephropathy, hyperlipidemia and presence of vitreomacular attachment
      (VMA) are factors associated with poor vision progress after intravitreal
      bevacizumab injection.

PMID- 23960891
TI  - Immediate changes in pupil size following Laser in situ keratomileusis (LASIK):
      Pupillometry study.
AB  - PURPOSE: To investigate the impact of laser in situ keratomileusis (LASIK) on the
      change in pupil size immediately after the procedure. METHODS: In a prospective
      study, measurement of pupil size was assessed in 70 eyes of 35 consecutive
      patients using a hand-held pupillometer before and immediately after LASIK in
      mesopic condition at the refractive eye center, Riyadh, Saudi Arabia. RESULTS:
      The pupil showed mild dilation immediate after LASIK. Mean pupil size before
      LASIK was 4.10 +/- 0.74 and immediate after was 4.74 +/- 0.82, P value <0.0001.
      No association was found with age, sex, central corneal thickness or pre
      operative refractive measurements (CCT). CONCLUSION: There is a change in pupil
      size that immerses immediately after LASIK; postulations suggested for pupillary
      dilation include the effect of suction ring, post-operative steroid eye drops,
      dark room, pain and anxiety.

PMID- 23960892
TI  - Current concepts in intravitreal drug therapy for diabetic retinopathy.
AB  - Diabetic retinopathy (DR) is a major cause of preventable blindness in the
      developed countries. Despite the advances in understanding and management of DR,
      it remains a challenging condition to manage. The standard of care for patients
      with DR include strict metabolic control of hyperglycemia, blood pressure
      control, normalization of serum lipids, prompt retinal laser photocoagulation and
      vitrectomy. For patients who respond poorly and who progressively lose vision in
      spite of the standard of care, intravitreal administration of steroids or/and
      anti-vascular endothelial growth factor (anti-VEGF) drugs appear to be a
      promising second-line of therapy. This review discusses the current concepts and
      the role of these novel therapeutic approaches in the management of DR. 

PMID- 23960893
TI  - Regression of aggressive corneal vascularization after photodynamic therapy,
      subconjunctival Avastin injections and topical cyclosporin-A 1% drops: A case
      report.
AB  - We describe a case of significant regression of aggressive, deep and superficial
      corneal vascularization using photodynamic therapy (PDT) with verteporfin,
      repeated subconjunctival injections of Avastin(r), plus topical cyclosporin-A 1%
      drops. The area of the corneal vascularization was treated with PDT with
      verteporfin. The subconjunctival space - next to the area of vascularization -
      was injected with Avastin(r) (1.25 mg/0.05 ml), immediately after PDT, and then
      for two more times during the follow-up period. The patient was kept on topical
      cyclosporin and prednisolone acetate. The outcome was evaluated clinically and
      photographically for 13 months. Corneal vascularization regressed significantly.
      No adverse effects were observed, neither locally or systemically. PDT with
      verteporfin, repeated subconjunctival injections of Avastin(r), and topical
      cyclosporin-A drops appear to be safe and effective in treating aggressive
      corneal vascularization. 

PMID- 23960894
TI  - Metastatic Squamous Spindle Cell Carcinoma of the conjunctiva.
AB  - Conjunctival Squamous Cell Carcinoma (CSCC) is one of the important ocular
      surface tumors. It is thought to be more advanced in this part of the world such
      as in Saudi Arabia. The Squamous Spindle Cell Carcinoma (SSCC) is a more
      aggressive variant. A single case of spindle squamous cell carcinoma tumor
      related death due to bone and lung metastasis has been reported in Sweden in
      1995. We are reporting a similar case of SSCC of the conjunctiva with eventual
      death because of bilateral lung metastasis in our area. Proper identification of
      this type of tumor by ocular pathologists and the need for future detailed
      clinicopathologic studies on CSCC in Saudi Arabia is emphasized. 

PMID- 23960895
TI  - Transient unilateral ophthalmoplegia without papilledema in a child with
      intracranial hypertension.
AB  - Intracranial hypertension is usually presented with papilledema and headache.
      Complete ophthalmoplegia without papilledema is a very rare finding of
      intracranial hypertension in children. A 5-year-old male patient with unilateral
      ophthalmoplegia due to increased intracranial pressure is presented. The
      fundoscopic examination and the magnetic resonance imaging of the brain were
      normal. He underwent lumboperitoneal shunt insertion for intracranial
      hypertension and the ophthalmoplegia was resolved one month later. Complete
      ophthalmoplegia without papilledema may occur following intracranial
      hypertension. Prompt and accurate diagnosis should be done and appropriate
      treatment to reduce the pressure should be performed to save the life of the
      children. 

PMID- 23960896
TI  - Thyroid associated orbitopathy: Understanding pathophysiology.

PMID- 23960898
TI  - Thyroid-associated orbitopathy: Current insights into the pathophysiology,
      immunology and management.
AB  - Half the patients suffering from Graves' disease develop thyroid-associated
      orbitopathy (TAO). The severity of TAO varies considerably with a mild form
      characterized by dry eyes and discomfort to the severe form with sight
      threatening exposure keratopathy and optic neuropathy. The pathogenesis and
      immunologic mechanisms underlying Graves' disease and TAO is unknown, however,
      advances toward this understanding have indicated a prominent role of orbital
      fibroblasts, T cells and B cells. These advances have led to novel strategies for
      clinical treatment using immunomodulatory modalities. Initial results included
      use of infliximab and etanercept (anti-TNF agents), but currently there is an
      increasing interest in anti-B cell (Rituximab) therapy. Rituximab has shown
      promising results in progressive, sight-threatening TAO. It has also shown
      encouraging results in halting or slowing the disease process in patients
      unresponsive to corticosteroids. The primary advantage of these immunomodulatory
      agents is based upon targeting the molecular mediators of the disease and
      avoiding the potential side effects of non-specific therapies. 

PMID- 23960897
TI  - Medical management of thyroid eye disease.
AB  - Thyroid eye disease (TED) is the most common cause of orbital disease in adults.
      The immunologic pathogenesis of TED has been an area of active research and
      considerable progress has resulted in an expansion of therapeutic options.
      Although surgical intervention may be required, a majority of TED patients can be
      managed with medical therapies. Of medical therapies, glucocorticoids remain the
      agent of choice in the control of TED activity. The objective of this review is
      to discuss the paradigm and options in medical management of TED. 

PMID- 23960899
TI  - Management of preseptal and orbital cellulitis.
AB  - Orbital cellulitis describes an infection involving the soft tissues posterior to
      the orbital septum, including the fat and muscle within the bony orbit. This
      condition may be associated with severe sight and life-threatening complications.
      Despite significant advances in antimicrobial therapies and diagnostic
      technologies, the management of orbital cellulitis often remains challenging, and
      rapid diagnosis and prompt initiation of therapy are important in minimizing
      complications and optimizing outcomes. This review summarizes the distinctive
      characteristics of preseptal and orbital cellulitis, with a focus on anatomic
      considerations, predisposing conditions, approaches to evaluation, and management
      strategies. 

PMID- 23960900
TI  - Internal cantholysis for full thickness eyelid defects.
AB  - Eyelid reconstruction requires an understanding of normal eyelid anatomy and
      function. A thorough understanding of the basic anatomy, contour, and mobility of
      the eyelids is essential in restoring the tissue to its presurgical level. There
      are many different surgical options to assist in the repair of full thickness
      eyelid defects involving the margin. Direct wound closure depends on eyelid
      laxity and is often possible with smaller defects. Moderate to larger sized
      defects are often under undue wound tension if direct closure is attempted. We
      have developed a new technique for closure of eyelid defects using a
      transconjunctival cantholysis to release the lateral canthal tendon cruces,
      thereby avoiding the external incision while still allowing for eyelid mobility.
      Using this technique for defects 15 mm in horizontal eyelid margin length or
      greater, we have found positive results. Direct closure of eyelid defects
      represents the most straightforward technique to repair any full-thickness eyelid
      defect and provides maximal functional and cosmetic results. Internal cantholysis
      represents an excellent option for repairing smaller and even larger full
      thickness eyelid defects. Eyelid mobility increases by 4-10 mm, sometimes more,
      and allows for closure of defects larger than even 20 mm. 

PMID- 23960902
TI  - Muller's Muscle Conjunctival Resection Ptosis Repair in the Aesthetic Patient.
AB  - Posterior eyelid ptosis repair via the Muller's muscle-conjunctival resection
      procedure is an effective, reliable, and simple technique for periorbital
      rejuvenation in the aesthetic patient. This procedure may be performed with other
      periorbital rejuvenation techniques without sacrificing results. Appropriate
      candidates are patients with maintained levator function whose ptotic upper
      eyelid elevates close to a normal eyelid level upon instillation of phenylephrine
      drops to the superior conjunctival fornix. 

PMID- 23960901
TI  - Dacryocystorhinostomy: History, evolution and future directions.
AB  - Dacryocystorhinostomy (DCR) is a procedure of choice for nasolacrimal duct
      obstruction and chronic dacryostenosis in the setting of patent canaliculi and a
      functional lacrimal pump. Two major approaches are utilized: external, via a
      transcutaneous incision and endonasal endoscopically guided. The surgery has a
      high success rate via both approaches. We review the history, evolution, current
      techniques, complications and future directions of DCR. 

PMID- 23960903
TI  - Utility of meibography in the evaluation of meibomian glands morphology in normal
      and diseased eyelids.
AB  - PURPOSE: To study the utility of meibography for the morphology of meibomian
      glands in normal eyelids and in various eyelid diseases. DESIGN: A cross
      sectional study. METHODS: A newly designed transilluminator, fitting both the
      upper along with lower eyelids, and an infrared camera were used to obtain video
      clips of the meibomian glands for 60 asymptomatic subjects with normal eyelid
      margin. Parameters studied included, ocular surface, Schirmer test, and tear
      breakup time (TBUT). The meibomian glands of patients with meibomian glands'
      abnormality secondary to infectious, inflammatory, malignant, congenital, or post
      radiation therapy disease related etiologies were compared with normal patients.
      Still pictures were extracted from the video clips to evaluate the meibomian
      glands for gland dropout and gross morphological changes. RESULTS: In normal
      subjects, meibomian glands appeared to be thinner and longer in the upper eye
      lids than in the lower eye lids. Gland dropout occured with increased age, more
      in the lower eye lid and in females. Excessive gland drop out (> 75%) was seen in
      patients with history of trachoma, Stevens Johnson syndrome, severe blepharitis,
      and post-radiation for orbital tumors. Variable gland drop out was noticed in
      patients with floppy eyelid syndrome, and blepharitis. In patients with
      congenital distichiasis, partial or complete gland drop out at the part of the
      eyelid margins affected by distichiasis was noticed. CONCLUSIONS: The newly
      designed transilluminator permitted the examination of both upper and lower eye
      lid meibomian glands with minimal discomfort. Evaluating the anatomical changes
      involving meibomian glands with meibography may help increase our understanding
      of the meibomian gland-related diseases, monitor the effects of treatment, and
      provide helpful information for patient education.

PMID- 23960904
TI  - Reconstructive options for the medial canthus and eyelids following tumor
      excision.
AB  - General principles provide the framework for eyelid and periorbital
      reconstruction following tumor excision. Eyelid tumors involving the medial
      canthus region and/or lacrimal system add to the complexity of reconstructive
      planning. The nature of the tumor, patient and tissue factors, and surgeon
      preference guide repair design choices. Reconstructive considerations and options
      following medial canthal tumor resection are described. 

PMID- 23960905
TI  - Lower eyelid swelling as a late complication of Bio-Alcamid filler into the malar
      area.
AB  - PURPOSE: To report the late complications associated with permanent filler
      injections into the malar area for rejuvenation. METHODS: A retrospective case
      series of three patients who presented with lower eyelid swelling several years
      following injection of polyalkylimide (Bio-Alcamid) into the malar area. RESULTS:
      All patients presented with lower eyelid swelling which developed as a result of
      spontaneous migration of filler to the lower eyelid. Iatrogenic migration of the
      filler from the lower eyelid following a trial to remove resulted in an abscess
      formation which further complicated the removal. CONCLUSIONS: Lower eyelid
      swelling may be one of the late complications associated with the permanent
      fillers into the malar area. An attempt at removal of filler by aspiration or
      bimanual expression may result in late migration of the product and the
      development of eyelid swelling.

PMID- 23960906
TI  - Bilateral subepidermal calcified nodules of the eyelid.
AB  - A subepidermal calcified nodule (SCN) is an uncommon benign lesion, which usually
      develops in early childhood and is typically solitary. A rare form of this lesion
      has been reported in the eyelid. We report here a case of a 12-year-old girl with
      bilateral nodules of the right upper eyelid and a left lower eyelid simulating
      epidermal cyst. The histopathologic examination of the excised nodule confirmed
      the diagnosis. To our knowledge, this may be the first bilateral case of eyelid
      SCN reported in the literature. 

PMID- 23960907
TI  - Acute spontaneous extraconal hematic cyst of the orbit.
AB  - A 49 year old man presented with one day history of mild right eye pain and
      proptosis. There was no definite history of trauma. On examination there was
      limitation of movement in all directions of gaze and 6 mm proptosis of his right
      eye. CT scan showed extraconal lesion compressing the optic nerve and inferior
      rectus muscle. Right inferior conjunctival fornix based approach was performed
      with lateral canthotomy and inferior cantholysis and exploration revealed a cyst
      containing blood which was removed. 

PMID- 23960908
TI  - Bilateral multiple primary iridociliary cysts - A rare case report.
AB  - Iridociliary cysts are often found in patients as an incidental finding during a
      routine ophthalmic evaluation and if asymptomatic do not require any treatment
      per se. However, these are often mistaken as iris melanoma and the patient is
      managed accordingly causing a great deal of inconvenience to the patient as well
      as the doctor. CASE PRESENTATION: A 69 year old male presented to the ophthalmic
      out-patients department for routine ophthalmic evaluation. On examination, he is
      best corrected visual acuity was 6/9, N6 in both eyes. Post-mydriasis evaluation
      showed a Grade II nuclear cataract in both eyes. There was a smooth, pigmented
      mass with a rounded surface projecting from behind the iris resembling an iris
      melanoma. On further evaluation, he was found to have multiple ciliary body
      cysts. CONCLUSION: Ultrasound biomicroscopy is a valuable technique in diagnosing
      iridociliary cysts.

PMID- 23960909
TI  - Eosinophilic granuloma: Presenting as a draining fistula.
AB  - A case report of an orbital eosinophilic granuloma presenting as a fistula in a
      15-year-old boy is presented. The patient had a history of a painful right upper
      eyelid swelling which required drainage and was considered as an abscess. An
      increase in swelling occurred and a small fistula appeared in the area
      subsequently. Computed tomography scan revealed a large soft tissue lesion in
      right superolateral orbit having intracranial extradural extension with
      destruction of bony orbital margin. Fine needle aspiration biopsy of the lesion
      revealed eosinophilic granuloma. A complete excision of the lesion was performed
      by a brow incision and histopathological examination of the excised specimen
      confirmed diagnosis. Although upper eyelid area eosinophilic granuloma is known
      to occur, its presentation as a fistula is not known. 

PMID- 23960910
TI  - Changing paradigms in the treatment of diabetic retinopathy.

PMID- 23960912
TI  - Advances in the treatment of diabetic retinopathy.
AB  - Diabetic retinopathy, the most common long-term complication of diabetes
      mellitus, remains one of the leading causes of blindness worldwide. Strict
      metabolic control, tight blood pressure control, laser photocoagulation, and
      vitrectomy remain the standard care for diabetic retinopathy. Focal/grid
      photocoagulation is a better treatment than intravitreal triamcinolone acetonide
      in eyes with diabetic macular edema and should be considered as the first-line
      therapeutic option. The current evidence suggests that intravitreal triamcinolone
      acetonide or anti-vascular endothelial growth factor agents result in a temporary
      improvement of visual acuity and a short-term reduction in central macular
      thickness in patients with refractory diabetic macular edema and are an effective
      adjunctive treatments to laser photocoagulation or vitrectomy. However,
      triamcinolone is associated with risks of elevated intraocular pressure and
      cataract. Vitrectomy with the removal of the posterior hyaloid without internal
      limiting membrane peeling seems to be effective in eyes with persistent diffuse
      diabetic macular edema, particularly in eyes with associated vitreomacular
      traction. Emerging therapies include islet cell transplantation, fenofibrate,
      ruboxistaurin, pharmacologic vitreolysis, rennin-angiotensin system blockers, and
      peroxisome proliferator-activated receptor gamma agonists. 

PMID- 23960911
TI  - Diabetic retinopathy - An update.
AB  - Management of diabetes should involve both systemic and ocular aspects. Control
      of hyperglycemia, hypertension and dyslipidemia are of major role in the
      management of diabetic retinopathy. In the ocular part; laser treatment remains
      the cornerstone of treatment of diabetic macular edema (focal/grid), severe non
      proliferative and proliferative diabetic retinopathy (panretinal
      photocoagulation). There is a strong support to combination therapy. Using one or
      two intravitreal injections such as anti-VEGF and or steroid to reduce central
      macular thickness followed by focal or grid laser to give a sustained response
      may offer an alternative to treatment in diabetic macular edema. Anti-VEGF were
      found to be effective as an adjunct therapy in proliferative diabetic retinopathy
      patient who is going to have vitrectomy for vitreous hemorrhage with
      neovascularization, panretinal photocoagulation, and other ocular surgery such as
      cases with neovascular glaucoma and cataract with refractory macular edema. 

PMID- 23960913
TI  - The management of diabetic macular oedema.
AB  - Diabetic macular oedema (DMO) is a significant cause of visual loss in the
      working population. Focal/grid photocoagulation remains an effective treatment
      for DMO and the benchmark to which clinicians compare other newer treatment
      modalities. There are, however, patients who do not respond adequately or who are
      refractory to laser photocoagulation. This has led to the development of newer
      treatments such as the intravitreal injection of vascular endothelial growth
      factor (VEGF) inhibitors as well as intravitreal corticosteroid releasing
      delivery systems. Cataract formation and raised intraocular pressure remain the
      major disadvantages of corticosteroid use. There is mounting evidence that
      intravitreal VEGF inhibitors with or without combined laser photocoagulation will
      become the gold standard treatment for DMO. 

PMID- 23960914
TI  - Microperimetry in diabetic retinopathy.
AB  - Diabetic retinopathy has an enormous impact on visual function, even before
      permanent visual acuity loss. Moreover, adequate functional tests are mandatory
      to diagnose and follow diabetic patients treated for diabetic macular edema
      (DME). More precisely, the visual function safety profile of any therapy for DME
      should be accurately investigated. Microperimetry offers the possibility to
      obtain an exact fundus-related quantification of retinal sensitivity, and it is
      changing the current approach to the functional investigation of diabetic
      retinopathy. 

PMID- 23960915
TI  - Magnetic resonance imaging of the retina: A brief historical and future
      perspective.
AB  - This invited review starts with a brief introduction of retinal anatomy and
      magnetic resonance imaging techniques with contrast to optics, followed by a
      history and future perspective on MRI applications to investigate the retinas of
      rodents, non-human primates and humans. 

PMID- 23960917
TI  - Orbital retinoblastoma: Present status and future challenges - A review.
AB  - Orbital retinoblastoma is a catastrophic event traditionally carrying a dismal
      prognosis. Although its incidence is less in the developed countries it continues
      to be one of the major diagnosis at presentation in the developing world. Orbital
      retinoblastoma encompasses a wide range of distinct clinical entities with
      varying tumor load. There are no standard treatment protocols as of now but the
      current preferred management is multimodal with a combination of initial high
      dose chemotherapy, surgery, external beam radiotherapy and prolonged chemotherapy
      for twelve cycles. In spite of progress on all fronts including surgical,
      medical, diagnostic, genetic and rehabilitative with improving survival rates,
      however, lack of access to medical facilities, lack of education about the need
      for early medical attention and cultural resistance to enucleation continue to
      contribute to an epidemic of extra ocular disease at diagnosis in the developing
      world. This review introduces the various terminologies used in the spectrum of
      orbital retinoblastoma, discusses in details the clinical aspects and management
      protocols, current status and the future directions. 

PMID- 23960918
TI  - Laser refractive surgery in glaucoma patients.
AB  - Glaucoma may not be an absolute contraindication to Laser-Assisted in situ
      Keratomileusis (LASIK), but so far it is a relative one. People who are glaucoma
      suspects or who have glaucoma are just as likely as any other to seek laser
      refractive surgery. LASIK is a popular ocular procedure, relatively pain free and
      it is carried out with an extremely precise computer-controlled excimer laser
      emission. On the other hand, glaucoma is a group of diseases manifested by optic
      nerve damage with visual field changes. Patients that undergo a transient but
      significant rise in intraocular pressure during LASIK procedure have risk of
      further optic nerve damage. Furthermore, steroids which are typically used after
      refractive surgery can increase intraocular pressure (IOP) especially in steroid
      responders, who are more prevalent among glaucoma patient. Glaucoma patients
      interested in LASIK surgery may visit a glaucoma specialist or another LASIK
      surgeon who has had experience with performing LASIK in glaucoma patients. PRK
      (photorefractive keratectomy), LASEK (laser epithelial keratomileusis) are good
      alternatives for glaucoma patients. Refractive surgeons might want to consider
      giving patients a photo of their optic nerve, or a drawing, or an objective
      record of their preoperative examination. 

PMID- 23960919
TI  - Pascal laser versus conventional laser for treatment of diabetic retinopathy.
AB  - PURPOSE: To compare the safety and efficacy of Pascal laser photocoagulation in
      comparison with the conventional laser photocoagulation in the treatment of
      diabetic retinopathy. PATIENTS AND METHODS: A prospective randomized case series
      study was done on 120 procedures done in 120 patients divided into two main
      groups, group A, patients undergoing focal or modified grid macular laser and
      group B, patients undergoing panretinal photocoagulation (PRP). Each of the two
      groups were subdivided into two subgroups randomly in the first we used
      conventional laser photocoagulation (groups A1 and B1) and in the other we used
      Pascal laser photocoagulation (groups A2 and B2). RESULTS: Procedures in groups
      A1,2 and in groups B1,2 had successful outcomes. Significantly higher powers were
      required with the Pascal (groups A2 and B2) than with conventional laser (groups
      A1 and B1) (p < 0.001) in eyes that underwent PRP and focal/modified grid macular
      treatment with both systems. No adverse events were noted in all groups.
      CONCLUSION: The Pascal photocoagulator is safe, rapid, effective, with rapid
      learning and had short exposure time. Although the shorter pulse duration of the
      Pascal necessitates the use of a higher power, it is not associated with adverse
      effects.

PMID- 23960916
TI  - Predicting visual outcomes for macular disease using optical coherence
      tomography.
AB  - In recent years, the management of macular disease has undergone radical changes,
      in part because of new therapeutic approaches, but also due to the introduction
      of a new imaging modality - optical coherence tomography (OCT). The application
      of OCT imaging has clarified many aspects of chorioretinal disease
      pathophysiology and elucidated many hitherto unrecognized disease
      characteristics. From an early stage in its development, OCT has also been
      revolutionary in attempting to extract clinically useful measurements from image
      data in an automated fashion. As a result, OCT-derived measurements of retinal
      thickness have been rapidly embraced in clinical and research settings. However,
      as knowledge of OCT image analysis has developed, it has become increasingly
      clear that even accurate measurements of retinal thickness may fail to predict
      visual outcomes for many diseases. As a result, the focus of much current
      clinical imaging research is on the identification of other OCT-derived anatomic
      biomarkers predictive of visual outcomes - such biomarkers could serve as
      surrogate endpoints in clinical trials and provide prognostic information in
      clinical practice. In this review, we begin by highlighting the importance of
      accurate visual function assessment and describing the fundamentals of OCT image
      evaluation, before describing the current state-of-the-art with regard to
      predicting visual outcomes, for a variety of macular diseases, using OCT. 

PMID- 23960920
TI  - Validation of patient symptom diary in acute posterior vitreous detachment.
AB  - PURPOSE: The purpose of the study is to determine the validity of an original
      patient symptom diary in recording symptoms of posterior vitreous detachment
      (PVD). METHODS: In this prospective cohort study, all patients presenting to the
      Hotel Dieu hospital emergency eye clinic between September 2008 and July 2009
      diagnosed with acute PVD were offered enrollment in the study. Patients were
      given the Queen's University posterior vitreous detachment patient diary at the
      initial visit after detailed eye examination, assessment of risk factors for
      retinal tears and detachments and a thorough explanation of their presenting
      complaints to record their symptoms related to PVD. At a random point during
      their six-week follow up, the patients were verbally asked the same questions
      being recorded in the diary over the phone. At the six-week follow up visit, the
      diaries were collected and the verbal results were compared with the written
      results. RESULTS: There was substantial to near perfect agreement between the
      verbal questions and written answers. Cohen's kappa scores for flash frequency,
      flash intensity, floater frequency, and floater type were 0.6229, 0.6389, 0.6495,
      and 0.8603, respectively. CONCLUSIONS: The Queen's University posterior vitreous
      detachment patient diary is a useful tool for investigating the quantity, quality
      and change in symptoms of patients presenting with PVD in the first 6 weeks of
      initial presentation.

PMID- 23960921
TI  - Visual outcome and complications of pars plana vitrectomy for dislocated
      intraocular lenses.
AB  - OBJECTIVE: To report factors predicting the visual outcome and complications in
      eyes that underwent pars plana vitrectomy (PPV) to manage dislocated intraocular
      lenses (IOLs). PATIENTS AND METHODS: A retrospective chart review was performed.
      Clinical data recorded from the patient charts include, demographic,
      preoperative, intraoperative, and postoperative, with emphasis on visual acuity,
      interval between IOL dislocation and pars plana vitrectomy, surgical method and
      complications. Patients with follow-up of less than three months were excluded.
      RESULTS: Ninety-four patients were identified, 63 males and 31 females. Age
      ranged from 2 to 85 years (mean 52.6). The range of follow-up was 3 to 108 months
      (mean +/- SD 19.4 +/- 17.4 months). The final visual acuity was 20/50 or better
      in 52 (55.3%) eyes. Our analysis indicated that visual rehabilitation with IOL
      was significantly associated with better visual acuity as compared with eyes that
      were left aphakic (P = 0.0092). There was a trend toward a better visual outcome
      when PPV was performed within two weeks from the diagnosis of the dislocated IOL
      which was associated with good visual outcome (20/200 or better) in 85.7% of eyes
      compared with 78.8% of eyes. Management of IOL by interofixation was associated
      in (90.0%) of eyes with good vision (20/200 or better) compared to 76.1% eyes
      that had exchange of IOL through the limbus. Postoperative complications include
      cystoid macular edema in 9 (9.6%), glaucoma in 9 (9.6%), bullous keratopathy in 8
      (8.5%), retinal detachments in 6 (6.4%) eyes, and relapsing uveitis in 2 (2%).
      CONCLUSION: In this series, the final visual outcomes were improved and the rate
      of postoperative complications were low. Eyes that were pseudophakic had
      significantly good visual outcome compared with eyes that were left aphakic. To
      the best of our knowledge, this may be the largest study on dislocated IOL
      removal by PPV with good visual results compared to other studies.

PMID- 23960922
TI  - Intravitreal bevacizumab for pediatric exudative retinal diseases.
AB  - PURPOSE: To detect if intravitreal bevacizumab can reduce retinal exudation,
      improve visual and anatomical outcomes, and facilitate the treatment in various
      pediatric exudative retinal diseases. PATIENTS AND METHODS: Prospective, non
      randomized, case series of nine eyes of pediatric exudative retinal diseases less
      than 18 years old which included six eyes with juvenile diabetic retinopathy, two
      eyes in children with Coats' disease, and one eye with myopic choroidal
      neovascular membrane (CNV). All eyes received only intravitreal bevacizumab
      injection 1.25 mg/0.05 ml as the primary treatment. The need for adjuvant
      ablative procedures, including laser photocoagulation or cryotherapy, were
      performed and recorded. The need for supplementary intravitreal bevacizumab
      injection was recorded. The changes in pre- and post-operative best-corrected
      visual acuity (BCVA) and central macular thickness (CMT) were recorded. Serial
      optical coherent tomography (OCT) and fundus flourescein angiography (FFA) were
      performed to follow treatment efficacy. RESULTS: The study included 19 eyes of 11
      patients with age equal to or less than eighteen years with exudative retinal
      diseases including type I DM (n = sixteen eyes), Coats' disease (n = 2 eyes), and
      due to myopic CNV (n = 1 eye). Mean pre-injection log MAR for all was 0.605 +/-
      0.174 and mean post-injection for all log MAR was 0.284 +/- 0.247. While Mean pre
      injection log MAR for DR and myopic CNV patients was 0.576 + 0.152 SD and mean
      post-injection log MAR for DR and myopic CNV patients was 0.229 + 0.189 at one
      year. Serial OCT measurements showed that mean CMT for all eyes was 355.8 +/-
      35.3 MUm SD at baseline, which was decreased to 222.42 + 26.2 MUm SD. The two
      eyes of Coats' disease needed another two supplementary intravitreal bevacizumab
      injections. No ocular or systemic complications related to bevacizumab were noted
      during the entire course of follow-up. CONCLUSION: Intravitreal bevacizumab
      appears to be a well-tolerated treatment for pediatric age group with various
      exudative retinal diseases. It has the potential as an adjuvant therapy for
      ablative procedures to improve final visual and anatomical outcome.

PMID- 23960923
TI  - Choroidal osteoma with CNVM - Successful treatment with intravitreal Bevacizumab.
AB  - Twenty-seven years old healthy woman presented with complaints of sudden painless
      blurred vision in right eye for 1 week. On examination, visual acuity was 20/30
      in the right eye and 20/20 in left eye. Fundus examination OS was normal; OD
      demonstrated a flat, opaque, yellowish parapapillary choroidal lesion with
      grayish membrane associated with minimal subretinal fluid suggestive of a CNVM in
      the center. B-scan ultrasonography revealed findings consistent with a choroidal
      osteoma. Fundus fluorescein angiography of the right eye revealed a relatively
      well-defined area of hyperfluorescence that increased in size and intensity in
      the later phases suggestive of active extrafoveal CNVM. Optical coherence
      tomography confirmed the extrafoveal CNVM with subfoveal fluid. She was treated
      with intravitreal Bevacizumab OD. At the 2 weeks visit, vision OD improved to
      20/20. The FFA and OCT revealed a resolved CNVM. Intravitreal Bevacizumab may be
      an effective alternative in the management of CNVM secondary to choroidal
      osteoma. 

PMID- 23960924
TI  - An overview of penetrating ocular trauma with retained intraocular foreign body.
AB  - Penetrating trauma is one of the common causes of ocular morbidity world wide.
      Violation of the globe integrity, also known as a ruptured globe is an ocular
      emergency that universally threatens vision. Prompt recognition and management is
      prudent. Here we report a case of a 26-year-old-female, university teacher, who
      presented with pain and sudden loss of vision in the left eye of 2 h duration
      subsequent to a test tube blast in the chemical laboratory. Examinations revealed
      a ruptured globe with vitreous haemorrhage and an intraocular glass foreign body
      in the left eye. Primary repair was done with good post operative visual
      recovery. We report this case to emphasize that protective measures should be
      taken to prevent such eye traumas. 

PMID- 23960925
TI  - A 14-year-old girl who regained normal vision after bilateral visual impairment
      following hot water injury to the eyes.
AB  - A 14-year-old girl presented with bilateral visual impairment following hot water
      injury to the eyes. The patient was admitted for a week and managed with guttae
      tropicamide 0.5% 8 h, diclofenac sodium 0.1% 4 h, and fluoroquinolone 0.3% 6 h
      and ointment chloramphenicol 8 h. Also, the patient was managed with capsule
      doxycycline 100 mg 12 h for 10 days, tablet cataflam 50 mg 12 h for 7 days and
      intramuscular tetanus toxoid 0.5 mg stat and dermacine cream for facial scald.
      The visual acuities improved from 3/60 (right eye) and 6/24 (left eye) to 6/6 in
      both eyes. There were resolutions of facial/eye pain, tearing, photophobia, lid
      edema, blepharospasm, and conjunctival hyperemia. There was complete healing of
      facial wounds and corneal ulcers. She was discharged from hospital on the 7th day
      of admission. Prompt presentation, degree of scald sustained, and appropriate
      medical intervention enhanced visual recovery and wound healing in the patient. 

PMID- 23960926
TI  - Corneal ectasia following LASIK.

PMID- 23960927
TI  - Limbal stem cell disease: Treatment and advances in technology.
AB  - Anterior segment stem cell technology, due to its already well-defined corneal
      limbal stem cells with greater ease of evaluation, has been at the forefront of
      ophthalmic stem cell treatment and technology since 1997. This paper provides an
      overview of the current standard of care for treatment of limbal stem-cell
      deficient conditions and reviews recent treatment technologies using ex vivo
      expansion of cultivated limbal stem cells of the cornea. 

PMID- 23960928
TI  - Cataract surgery with femtosecond lasers.
AB  - Cataract surgery with femtosecond lasers is approaching its practical application
      in ophthalmology. These lasers, working in the near infrared wavelength (1030 nm)
      can penetrate the transparent and even opaque tissues of the anterior segment of
      the eye, with limitations related to vessels and mineral opacities. Femtosecond
      lasers, guided by image systems can precisely outline the anatomy of the anterior
      segment of the eye, acting in a very precise way, performing corneal incisions,
      capsulorhexis, softening and breaking of the nucleus, which are essential steps
      in cataract surgery. In this article we summarize the four technologies available
      and approaching commercial application in the coming future. The main differences
      between the systems are based on the diagnostic imaging techniques, which might
      either be based on optical coherence tomography or the Scheimpflug principles.
      One model (the Technolas Femtec 520 F custom lens, 20/10 Perfect Vision), offers
      the possibility of combined use in corneal and intraocular surgery. While
      clinical studies are being performed with all of them, and most probably becoming
      available on the market during 2011 and 2012, the main problem of this emerging
      technology is its practical application as the increase in costs will affect
      their availability in the market of cataract surgery. Research is needed to
      confirm the practicality and the advantages of femtosecond laser cataract surgery
      over conventional surgery. Meanwhile, a new path for the future of cataract
      surgery is opening. 

PMID- 23960929
TI  - Late onset corneal ectasia after LASIK surgery.
AB  - PURPOSE: To report late onset corneal ectasia following myopic LASIK. METHODS: A
      retrospective cohort case series. Nineteen patients with late onset corneal
      ectasia following LASIK procedure were examined at The Eye Center, Riyadh, Saudi
      Arabia. Patients underwent LASIK for myopia with spherical equivalent ranging
      from -1.4 to -13.75 diopters. Age and gender, history of systemic or local
      diseases, and time of onset of corneal ectasia were recorded. Eye examination and
      corneal topographical analyses were done before and after LASIK surgery. RESULTS:
      Nineteen patients (29 eyes) with late onset corneal ectasia were identified from
      1998 to 2008 in 13 male and six female patients. The mean follow-up period was
      108 +/- 23 months (range 72-144 months). No patient had pre-operative
      identifiable risk factors for corneal ectasia and the mean time of onset was 57
      +/- 24 months (range 24-120 months after LASIK). The pre-operative values
      included mean central pachymetry 553 +/- 25 MUm, mean keratometry reading of 42.9
      +/- 1.5 diopters, average oblique cylinder of 1.4 +/- 1.2 diopters, posterior
      surface elevation of 26 +/- 2.1 diopters, corneal flap thickness of 160 MUm, mean
      spherical equivalent of -5.6 +/- 3.6 diopters, and calculated residual corneal
      stromal bed thickness was 288 +/- 35 MUm. Three (5 eyes) patients developed
      ectasia after pregnancy. Three (4 eyes) patients developed corneal ectasia
      following severe adenoviral keratoconjunctivitis and had positive PCR for
      adenovirus type 8. CONCLUSIONS: Corneal ectasia may develop many years after
      LASIK surgery and symptoms could go undetected for some time. Pregnancy and
      adenoviral keratoconjunctivitis occurred post-operatively in six patients.

PMID- 23960930
TI  - Ocular mycosis at a referral center in Saudi Arabia: A 20-year study.
AB  - PURPOSE: To review the clinical experience of fungal keratitis cases at King
      Khaled Eye Specialist Hospital (KKESH) in Riyadh, Saudi Arabia. METHODS:
      Retrospective observational review and analysis of 124 patient charts with
      confirmed diagnosis of fungal keratitis between 1984 and 2004. RESULTS: One
      hundred and twenty four eyes of 124 patients had proven fungal infection; 101
      eyes had fungal keratitis and 23 eyes had fungal endophthalmitis complicating
      keratitis. Estimated proportion of fungal keratitis and endophthalmitis was
      10.3%. Mean age was 55 years with male predominance (79.0%). Commonly associated
      factors were previous intraocular surgery (38.7%) and trauma (20.9%). Major risk
      factor for progressing to endophthalmitis was previous intraocular surgery
      (65.2%), p < 0.001. Initial laboratory results were fungal positive only in 30.6%
      (p < 0.001). Commonest organisms isolated were Aspergillus spp. (29.8%) followed
      by Trichophyton sp. (16.1%), then Candida and Fusarium sp. Comparison of both
      phases of the study showed improvement in the rate of successfully treated cases
      from 34.6% to 58.3%, and a decline in cases progressing to endophthalmitis from
      25.0% to 13.9%. Therapeutic penetrating keratoplasty increased from 26.9% to
      73.6% (p < 0.001). Thirteen eyes required enucleation or evisceration.
      CONCLUSIONS: In contrast to other studies on fungal keratitis, Aspergillusspp.
      and Trichophyton sp. were the most commonly isolated fungal pathogens; the former
      carries the worst prognosis. Risk factors included previous intraocular surgery
      and trauma. Poor outcome was associated with Aspergillus spp., delayed
      presentation, previous intraocular surgery and late surgical intervention. This
      study recommends early surgical intervention to improve the outcome.

PMID- 23960931
TI  - Intraoperative flap complications in laser in situ keratomileusis with two types
      of microkeratomes.
AB  - PURPOSE: To determine the incidence and types of intraoperative flap
      complications in laser in situ keratomileusis (LASIK) encountered with the
      Hansatome microkeratome and the Moria microkeratome. METHODS: In this
      retrospective case series, all patients with intraoperative flap complications
      who were treated between June 1999 and July 2008 at the Eye Consultants Center in
      Riyadh, Saudi Arabia, were identified and reviewed. RESULTS: Of the 4352 subjects
      who underwent bilateral primary LASIK procedure, intraoperative microkeratome
      complications were detected in 89 eyes of 83 patients. The overall incidence of
      flap complications was 89/8704 (1.00%): incomplete flaps occurred in 53 eyes
      (0.60%), followed by buttonhole flaps in 17 eyes (0.19%), free complete flaps in
      10 eyes (0.11%), free partial flaps in 6 eyes (0.07%), sluffed epithelium in 2
      eyes (0.023%), and a splitted flap (vertical flap cut) in 1 eye (0.01%). The
      incidence rates of intraoperative flap complications with the Hansatome
      microkeratome and the Moria microkeratome were 1.21% (41/3378) and 0.90%
      (48/5326), respectively (P = 0.19). There was a statistically significant
      difference between the two microkeratomes with regard to the incidence of
      buttonhole flaps: 0.33% (11/3378) for the Hansatome microkeratome versus 0.11%
      (6/5326) for the Moria microkeratome (P = 0.04). CONCLUSION: Generally, the
      incidence rates of intraoperative flap complications with the Hansatome
      microkeratome and the Moria microkeratome were similar. However, buttonhole flaps
      occurred more often with the Hansatome microkeratome (a type of microkeratome
      that produces larger flaps). The commonest complication encountered was the
      incomplete flap, followed by the buttonhole flap and free flap.

PMID- 23960932
TI  - Glued intraocular lens implantation for eyes with defective capsules: A
      retrospective analysis of anatomical and functional outcome.
AB  - PURPOSE: To analyze the anatomical and functional outcome of glued intra ocular
      lens (IOL) implantation technique and its modifications. DESIGN: Retrospective
      observational case series. METHODS: This is a retrospective analysis of the
      patients who underwent glued intra ocular lens implantation from December 2007 to
      August 2010. Post operative uncorrected vision, best corrected visual acuity
      (BCVA), intra ocular pressure, IOL position, endothelial cells and anterior
      chamber reaction at their last follow up are analyzed from their concerned case
      sheets documentation. Subjective changes are analyzed via individual
      questionnaire. Immediate and late postoperative complications are also evaluated.
      Surgical modifications and the difference in the operated eyes are analyzed.
      RESULTS: Total 210 glued IOL eyes have been reviewed. Out of this 210, there are
      152 (PMMA glued IOL), 21 (three piece foldable IOL), 5 (multifocal foldable IOL),
      12 (pediatric glued IOL), 5 (20G sutureless vitrectomy), 2 (glued iris
      prosthesis) and 3 (transposition of posterior chamber IOL into anterior chamber).
      In combined surgeries there are, 5 (optical penetrating keratoplasty), 2
      (descemet's stripping endothelial keratoplasty) and 3 (iridoplasty). The
      modifications in glued IOL are handshake technique, injectable or foldable glued
      IOL, Multifocal glued IOL and intraoperative 23/25G trocar cannula infusion.
      Decentration (1.97%), macular edema (1.97%) and optic capture (2.63%) are the
      post operative complications encountered in rigid glued IOL. Good patient
      satisfaction is seen in the eyes with IOL repositioning, IOL exchange and
      multifocal glued IOL. There is significant improvement in BCVA in PMMA IOL (p =
      1.35 * 10(-5)) and foldable IOL (p = 0.000). CONCLUSION: Glued IOL seems to be a
      good alternative in IOL implantation in eyes with deficient capsules. The
      modifications in the existing technique decrease the learning time and risk for
      complications.

PMID- 23960933
TI  - Anterior chamber depth in normal subjects by rotating scheimpflug imaging.
AB  - PURPOSE: Anterior chamber depth (ACD) is an important preoperative parameter in
      anterior segment surgery. Several factors are known to influence ACD, including
      race and geography. Our purpose was to sample data from various countries to
      characterize differences in ACD worldwide and, if any, assess their level of
      clinical significance. SETTING: International, multicenter. METHODS: Cross
      sectional study. Using the Pentacam Eye Scanner (OCULUS GmbH, Wetzlar, Germany),
      we analyzed ACD measurements from 1077 eyes of 568 normal adults from nine
      countries spanning six continents. Differences between countries were assessed by
      comparison of 95% confidence intervals and by ANOVA. Normative thresholds were
      constructed at three standard deviations (SD) above and below the mean. RESULTS:
      Mean ACD was 3.11 mm overall, ranging from 2.91 mm (New Zealand) to 3.24 mm
      (United States). The ACD among New Zealanders was significantly shallower (P <
      .0001) than that among Chinese, Egyptians, Germans, Indians, and Americans. The
      maximum difference in the mean ACDs was 0.33 mm, between New Zealand and the
      United States. The shallowest 0.15% of normal ACD values occurred below 2.04 mm
      overall, ranging from 1.69 mm (New Zealand) to 2.42 mm (United States). The
      deepest 0.15% of normal ACD values occurred above 4.18 mm overall, ranging from
      4.03 mm (Saudi Arabia) to 4.35 mm (Brazil). CONCLUSIONS: ACD did not vary
      significantly in the countries studied, with the notable exception of New
      Zealand. Surgeons should anticipate a greater likelihood of a shallow ACD when
      evaluating patients from New Zealand. Clinical examination and direct measurement
      of ACD are recommended. Finally, deep ACD has limited clinical utility in
      screening for keratoconus.

PMID- 23960934
TI  - Femtosecond-UVA-riboflavin (FUR) cross-linking approach to penetrating
      keratoplasty and anterior lamellar keratoplasty.
AB  - PURPOSE: To introduce femtosecond laser wound design combined with
      riboflavin/ultraviolet light-A (UVA) collagen cross-linking at the wound for
      penetrating (PKP) and anterior lamellar keratoplasty (ALK). Primary outcomes were
      intraocular pressure (IOP in mmHg) at burst point for the PKP group, and tensile
      strength (kPa) until dehiscence for the ALK group. METHODS: Human corneoscleral
      rims (N = 20) were mounted on artificial anterior chambers. PKP specimens
      underwent FUR, femtosecond laser-cut without cross-linking, or conventional
      corneal transplantation. PKP maximum burst IOP with progressive suture removal
      was assessed by a digital manometer, in triplicate and by three observers. ALK
      involved whole human globes (N = 10) divided into three groups using a 200
      micron, 8 mm diameter donor lenticule, with or without cross-linking. Cross
      linked specimens were exposed to UVA light (3 mW/cm(2) irradiance, 3.4 J, 370 nm
      wavelength) for 30 min with 0.1% riboflavin (20% Dextran) applied every 2-min.
      ALK tensile strength was determined using a digital tensiometer. RESULTS: In PKP,
      burst IOP was 31.32 mmHg greater for corneas that underwent the UVA-riboflavin
      treatment than for those that did not (p < 0.05). There was no significant
      relationship (p = 0.719) established between cut design (femtosecond versus
      conventional). On multivariate analysis, there was a mean of 15.82 mmHg higher
      sustainable pressure for each stabilization suture present (p < 0.0001). In ALK,
      specimens comprised of human donor and human recipient tissue combined with UVA
      riboflavin therapy experienced the greatest level of adhesion strength (954.7 +/-
      290.4 kPa) as shown by the force required to separate the tissues, and compared
      to non-cross-linked specimens. Electron microscopy of ALK specimens showed non
      fused and fused longitudinal cross-linked collagen fibers as well as bridges,
      densities, attachment plaques and primitive plasmalemmal densities. CONCLUSIONS:
      Cross-linking effects of the FUR technique enable a stronger graft-recipient
      adhesion compared to conventional penetrating and anterior lamellar keratoplasty.
      Electron microscopy enabled visualization of cross-linked interface and potential
      bonding. The FUR approach may further lead to sutureless transplantation
      techniques in the future. SETTING/VENUE: ImagePlus Laser Eye Centre, Winnipeg,
      and University of Ottawa Eye Institute, Ottawa, Canada.

PMID- 23960935
TI  - Mushroom keratoplasty in pediatric patients.
AB  - OBJECTIVE: To report the outcome of mushroom keratoplasty for the treatment of
      full thickness corneal disease in pediatric patients with healthy endothelium.
      METHODS: A retrospective analysis of pediatric patients who underwent mushroom
      keratoplasty. The medical records of pediatric patients suffering from full
      thickness corneal stromal disease with normal endothelium who underwent mushroom
      keratoplasty at our Institution were included. A two-piece donor graft consisting
      of a large anterior stromal lamella (9.0 mm in diameter and +/-250 MUm in
      thickness) and a small posterior lamella (5-6.5 mm in diameter) including deep
      stroma and endothelium, prepared with the aid of a microkeratome had been
      transplanted in all cases. Ophthalmic examination including slit lamp
      examination, best corrected visual acuity, and corneal topography was performed
      preoperatively and at each postoperative visit on all patients. The endothelial
      cells were assessed by specular microscopy in these patients. RESULTS: Six eyes
      of six patients (five males and one female) were included. The mean age was 9.3
      years (range 5-15 years). Average follow-up was 17.8 months (range 9-48 months).
      There were no early or late complications recorded. All corneas were clear at the
      last follow up visit. Preoperative best corrected visual acuity (BCVA) was worse
      than 20/70 in all six eyes. Postoperatively, four eyes achieved BCVA of 20/40 or
      better. Endothelial cell loss (n eyes = 3 averaged 24% (range 19-31%). The mean
      endothelial cell loss was 24% (range 19-31%) among these patients. CONCLUSIONS:
      Microkeratome assisted mushroom keratoplasty is a viable surgical option for
      pediatric eyes with full thickness corneal stromal disease and healthy
      endothelium. Mushroom keratoplasty combines the refractive advantage of a large
      penetrating keratoplasty with the survival advantage of a small penetrating
      keratoplasty. Furthermore, mushroom keratoplasty exhibits the mechanical
      advantage of a shaped keratoplasty.

PMID- 23960936
TI  - Effects of advanced surface ablations and intralase femtosecond LASIK on higher
      order aberrations and visual acuity outcome.
AB  - BACKGROUND/AIMS: To study the changes in wavefront (ocular) and corneal higher
      order aberrations (HOAs) and visual acuity (VA) outcome following wavefront
      guided advanced surface ablation (ASA) techniques and intralase femtosecond LASIK
      (iLASIK) in myopia treatment. METHODS: Ocular aberration and corneal topography
      of 240 eyes in the ASA techniques (this was equally divided into a flap-on group
      where the epithelial flap was preserved and reapplied to the photoablated stromal
      bed and a flap-off group when the epithelial flap was discarded during the
      procedure), and 138 eyes in the iLASIK group were obtained before and 3 months
      following treatment. The correlation of aberrations with best spectacle-corrected
      visual acuity was analyzed. RESULTS: At 3 months, there was statistically
      significant (P < 0.001) surgically induced increase in spherical aberration (SA)
      in each of the techniques for both ocular and corneal analysis. iLASIK induced
      significantly less ocular and corneal HOAs (P < 0.001). The mean manifest
      refractive spherical equivalent was closer to attempted correction compared to
      other groups (P < 0.001). Eighty-three eyes (70%) of flap-on, 80 (67%) flap-off
      and 94 eyes (68%) in the iLASIK group achieved 20/20 uncorrected VA. Fifteen eyes
      (11%) accomplished 20/12.5 or better in iLASIK compared to 4 (3%) for flap-on and
      7 (6%) for flap-off ASA group. Only the flap-off treatment showed a consistent
      correlation between the corrected aberrations and visual performance. CONCLUSION:
      At 3 months, all procedures resulted in a significant increase in HOAs and SA.
      All had comparable 20/20 VA and 11% of iLASIK patients achieved 20/12.5 or better
      level.

PMID- 23960937
TI  - Outcomes with the Boston Type 1 Keratoprosthesis at Instituto de Microcirugia
      Ocular IMO.
AB  - PURPOSE: To report the outcomes on the Boston Type 1 Keratoprosthesis at our
      institution. DESIGN: Retrospective analysis case series. PARTICIPANTS: We
      analyzed 54 eyes of 53 patients who previously underwent Boston Type 1
      Keratoprosthesis surgery at our institution from July 2006 to March 2011.
      METHODS: Preoperative and postoperative parameters were collected and analyzed.
      MAIN OUTCOME MEASURES: Visual acuity and keratoprosthesis stability. RESULTS:
      Common preoperative diagnoses were penetrating keratoplasty failure in 49 eyes
      (90.7%), chronic keratitis in 2 eyes (3.7%), ocular cicatricial pemphigoid in 1
      eye (1.85%), Stevens Johnson syndrome in 1 eye (1.85%) and corneal
      vascularization in 1 eye (1.85%). Additionally, 40 eyes (74%) had preoperative
      glaucoma, and an Ahmed valve was implanted in 55% of them. Preoperative BCVA
      ranged from 20/200 to light perception. At an average follow-up of 20.15 months
      +/- 12.7 (range, 1-56), postoperative vision improved to ?20/200 in 18 eyes
      (33.3%) and ?20/50 in 4 eyes (7.4%). The graft retention was 96%. CONCLUSIONS:
      The Boston Type 1 keratoprosthesis is a valid option for high-risk patients. The
      design improvements in the Boston keratoprosthesis, as well as the daily
      implementation of the therapeutic methods, have notably diminished occurrence of
      the most serious complications, such as corneal necrosis and endophthalmitis. As
      such, glaucoma and its subsequent complications now stand as the most prevalent
      prognostic factor in the long term.

PMID- 23960938
TI  - Corneal graft rejection in African Americans at Howard University Hospital.
AB  - PURPOSE: There is scarcity of data in the literature on cornel graft rejection
      rate in patients exclusively of African ancestry. The purpose of this study was
      to evaluate the rejection rate of corneal transplant surgery performed at Howard
      University Hospital on such patients over a 15 year period. DESIGN: A
      retrospective evaluation was performed of the cornea graft rejection and corneal
      graft failure rate in 125 penetrating keratoplasties (PKPs) done by one corneal
      specialist at Howard University Hospital from January 1, 1990 to August 31, 2005.
      METHODS: Of the 125 patients, 62 were eliminated from the study because of re
      grafted eyes, non-African descent, primary graft failures, follow-up less than 1
      month and lack of availability of charts. This study, therefore, studied and
      recorded data from 63 penetrating keratoplasties of 63 eyes from 60 patients.
      RESULTS: Episodes of graft rejection were documented in 23 eyes (36.5% of cases).
      Nine out of the 23 graft rejections manifested to secondary graft failure (39%).
      Overall, there were nine out of the 63 PKPs (14.3%) that resulted in secondary
      graft failure over the past 15 years. The major diagnostic categories were
      bullous keratopathy 24 (38%), keratoconus 10 (15.8%), Fuch's dystrophy 4 (6.3%),
      other 20 (31.7%). Of the cases with episodes of rejection and failure, 4.3% and
      none were attributable to keratoconus, 30.4% and 22.2% for bullous keratopathy,
      and 8.7% and 22.2% for Fuch's dystrophy, respectively. Also, best visual acuity
      was looked at in patients with rejection episodes. None of the patients had a pre
      op visual acuity 20/40 or better; however, post-op PKP 2 (8.7%) of patients
      achieved 20/40 or better. Also, 4 (17.4%) of patients had a pre-op visual acuity
      between 20/50 and 20/150, but post-op PKP best visual acuity between 20/50 and
      20/150 was increased to 9 (39.1%). CONCLUSION: At 36% the prevalence of corneal
      graft rejection was one of the highest in the reported literature. But only 14%
      of those episodes resulted in graft failure which is one of the lowest in the
      published literature. This study demonstrates that patients of African ancestry
      may have a higher rejection rate which does not necessarily result in graft
      failure.

PMID- 23960939
TI  - Ocular complications of severe vernal keratoconjunctivitis (VKC) in Yemen.
AB  - OBJECTIVES: The objective of this study was to assess the ocular complications
      and visual loss among patients with severe vernal keratoconjunctivitis (VKC).
      METHODS: Four hundred and thirty-one patients with VKC seen at Ibn Al-Haitham Eye
      Center were the study group. This is a retrospective non-comparative
      observational study between 01 January 2002 and 31 December 2002. Visual acuity
      was measured with the standard Snellen visual acuity chart and for children under
      5 years of age Kay pictures were used. Visual impairment was assessed by means of
      the World Health Organization criteria for visual disabilities. Cases with severe
      VKC that developed ocular complications leading to blindness and severe visual
      impairment were analyzed. RESULTS: The majority of VKC patients were males
      (75.9%) with a male:female ratio of 3.1:1. A total of 68 (15.7%) patients (54
      boys and 14 girls) had severe VKC. The ocular findings among 20 patients with
      severe VKC that led to blindness and severe visual impairment included
      keratoconus (7); steroid-induced cataract (5), central corneal scars (5) and
      steroid-induced glaucoma (3). Two of the keratoconus cases developed acute
      hydrops. CONCLUSION: Severe VKC in developing countries including Yemen is a
      potentially blinding disease. Visual loss may be due to keratoconus and corneal
      scars, as well as complications of the unsupervised use of topically administered
      corticosteroids.

PMID- 23960940
TI  - The outcome of congenital cataract surgery in Kuwait.
AB  - AIM: Congenital cataract is the most common cause of treatable blindness in
      children and the outcome of congenital cataract surgery has not been studied in
      Kuwait, so the purpose of this study is to evaluate the visual outcome and the
      postoperative complications. METHODS: Medical records of children who underwent
      congenital cataract surgery between September 2000 and December 2008 at Al-Bahar
      Eye Center, Ministry of Health of Kuwait were retrospectively reviewed. In 100
      eyes that fill the inclusion criteria visual acuity and postoperative
      complications were recorded. The mean follow up was 3.9 +/- 1.7 years with range
      from 3 to 6 years. RESULTS: The mean age of congenital/developmental cataract
      surgery is 8.9 +/- 8.7 months for bilateral cases and it was 5.75 +/- 4.61 months
      for unilateral cases. The mean final postoperative BCVA in unilateral cases was
      1.0 (20/200) log MAR unit and it was 0.3 (20/40) log MAR unit for the bilateral
      cases. Four percent of the cases developed postoperative glaucoma and 2% of them
      developed significant opacification of the posterior capsule. CONCLUSION: Our
      findings provide evidence of recent improvement over time in the visual prognosis
      in bilateral, and to a lesser degree, unilateral cataract, in children in Kuwait.

PMID- 23960941
TI  - Spontaneous attachment of detached donor-corneal graft following Descemet's
      stripping automated endothelial keratoplasty.
AB  - This case report presents a case that had Descemet's stripping automated
      endothelial keratoplasty complicated postoperatively by detached donor grafts.
      The patient had a well centered partially detached graft that attached
      spontaneously the next day without the need to re-bubble. Postoperatively he had
      a clear cornea, improved uncorrected visual acuity with good endothelial cell
      count. It is worth waiting for a partially detached well centered graft to adhere
      spontaneously; this would lower the possible risks of repeated anterior chamber
      air injections. Cases should be selected to eliminate any mechanical factor that
      would prevent the attachment. 

PMID- 23960942
TI  - Peripheral sterile corneal infiltrate in two brothers after photorefractive
      keratectomy.
AB  - This is a report of two brothers who underwent bilateral photorefractive
      keratectomy and developed bilateral peripheral corneal infiltrate on the third
      day following surgery. The patients were treated with antibiotics and low
      concentration steroid until negative culture was reported 48 h later, when
      intensive topical steroid was started. The infiltrate resolved by day 10 with
      residual subepithelial haze that was apparent 8 months after surgery. Sterile
      infiltrate has been reported as complication of photorefractive keratectomy and
      can be managed successfully with excellent outcome. The fact that it happened in
      two brothers may raise the possibility of genetic predisposition. 

PMID- 23960943
TI  - Anterior capsule tear after laser iridotomy complicating phacoemulsification.
AB  - A 70-year-old Indian lady had a history of bilateral laser peripheral iridotomy
      (LPI) for primary angle closure. Subsequently she developed cataract in both the
      eyes. Right eye cataract surgery was complicated by an anterior capsule rupture,
      which was discovered intra-operatively at the site of the LPI. Trypan blue was
      used to stain the anterior capsule to delineate the anterior capsule defect. An
      attempt at continuous curvilinear capsulorhexis was unsuccessful, and the
      anterior capsulotomy was completed with scissors. To the best of our knowledge
      the surgical management of cataract in the presence of anterior capsule rupture
      as a result of LPI has not been reported. Awareness of this potential
      complication of LPI will aid in planning for successful phacoemulsification
      cataract surgery. 

PMID- 23960944
TI  - Glaucoma, challenges and opportunities.

PMID- 23960946
TI  - A review of canaloplasty.
AB  - Canaloplasty is a method of lowering intraocular pressure (IOP) by which a
      flexible, beacon-tipped microcatheter equipped with an ophthalmic viscosurgical
      device (OVD) delivery system is used to catheterize and introduce a suture into
      Schlemm's canal. Ligation of this suture provides tension on the canal and
      facilitates aqueous outflow. Canaloplasty is designed to be a blebless procedure
      that requires no antifibrotic agents and has been shown to safely and effectively
      lower IOP in patients with open-angle glaucoma (OAG) with minimal complications.
      Most importantly, no bleb-related adverse events are associated with this
      procedure. When contemplating surgical management of OAG, canaloplasty may be
      considered. 

PMID- 23960945
TI  - Ahmed glaucoma valve in children: A review.
AB  - Pediatric glaucoma is potentially a blinding disease. Although goniotomy and
      trabeculotomy are associated with good early success rates, eventually 20% of
      these procedures fail and many children will require additional surgery to
      control the IOP in the long-term. In this review, we reported that adequate IOP
      control can be achieved with the placement of Ahmed glaucoma valve and can last 5
      or more years. However, most patients will need one or more glaucoma medications
      at some point after surgery. In addition, the implants may be associated with
      pupillary irregularities, lenticular opacification as well as tube-related
      complications, particularly in the first year of life, as the globe is enlarging
      with age. 

PMID- 23960947
TI  - Primary lens extraction for glaucoma management: A review article.
AB  - Recently, primary lens extraction alone gained more acceptance as an alternative
      surgical approach for glaucoma management. This view was supported by the
      advances in phacoemulsification and intraocular lenses with greater safety and
      visual recovery, in addition to a substantial reduction of intraocular pressure
      and deepening of the anterior chamber and filtration angle. The decrease in IOP
      after cataract surgery in primary open-angle glaucoma (POAG) is mild, less
      predictable, related to baseline levels, and may return to presurgical values
      after an initial period of reduction. Therefore, the IOP-lowering effect of
      primary cataract extraction in POAG may be insufficient to achieve adequate IOP
      control. The IOP reduction after lens extraction is consistently greater in eyes
      with primary angle closure glaucoma (PACG) than in eyes with POAG. Primary lens
      extraction in acute PACG eliminates, or at least, reduces the risk of recurrence
      of acute attacks and deepens the anterior chamber and widens the angle which
      reduces the risk of progression of peripheral anterior synechiae and development
      of chronic PACG. Primary lens extraction may be more preferable to glaucoma
      incisional surgery in mild to moderate PACG eyes with appositional angle closure.
      The decision to do lens extraction as a primary treatment for glaucoma should be
      individualized based upon several factors other than the effect on IOP. These
      factors include patients' characteristics, surgeons' skills and preferences,
      status of glaucoma control, type of cataract and intraocular lens implanted, and
      potential harm of laser treatment for late capsular opacification and fibrosis. 

PMID- 23960948
TI  - Review: The role of LOXL1 in exfoliation syndrome/glaucoma.
AB  - Exfoliation syndrome is a common cause of open-angle glaucoma. It is
      characterized by microscopic flakes of protein-rich material being deposited in
      both ocular and non-ocular tissues. While its mechanism is poorly understood,
      family- and population-based studies have established that the disorder has a
      strong genetic component. A further understanding of the relevant gene variants
      might help reveal the molecular mechanism behind exfoliation. The most-strongly
      associated genetic variants are found in the lysyl oxidase-like 1 (LOXL1) gene.
      However, two major risk alleles in the LOXL1 coding region are reversed between
      ethnic groups. It now appears the strong association between LOXL1 and XFS is due
      to non-coding variants that have not yet been identified. Such variants might
      alter LOXL1 expression, which is decreased in the late stages of exfoliation
      syndrome/glaucoma. Here we discuss LOXL1 as a risk gene for exfoliation syndrome
      and glaucoma. 

PMID- 23960949
TI  - Gene therapy strategies in glaucoma and application for steroid-induced
      hypertension.
AB  - Gene therapy of the eye has a high potential of becoming the preferred treatment
      of a number of eye diseases. Because of its easy accessibility, all the tissues
      of the eye can be reached and genetically manipulated with nowadays standard gene
      delivery technologies. Gene therapy offers the possibility to do both, correct a
      genetic defect by replacing the mutated or missing gene and that of using genes
      as drugs. Gene drugs would be more specific and would have a longer duration of
      action and less toxicity than conventional drugs. Examples of both applications
      are beginning to emerge. Using gene replacement, vision has been restored in
      several patients of Leber congenital amaurosis (Maguire et al., 2009). Some gene
      drugs, such as siRNA, are currently in clinical trials to silence angiogenic
      factors in macular degeneration (Campa and Harding, 2011). In this manuscript we
      first give a short overview of the basics of gene therapy in the eye and then
      review the ongoing preclinical studies in our laboratory for the gene-drug
      treatment of steroid-induced ocular hypertension. 

PMID- 23960950
TI  - High resolution in vivo imaging of the lamina cribrosa.
AB  - The lamina cribrosa (LC) is considered to be the principal site of retinal
      ganglion cell axon injury in glaucoma. Imaging technology has steadily improved
      in recent years, allowing greater resolution of fine details of laminar
      structure. Histological studies have elucidated the details of LC structure, both
      in normal and glaucomatous eyes, but such studies are limited by smaller sample
      size, greater difficulty of conducting prospective studies, and possibility of
      altered tissue architecture during histologic processing. We reviewed the
      literature describing the LC in primate and human eyes using in vivo imaging
      devices and provided a brief explanation of the imaging technology and main
      results of the articles. We also discuss the advantages and limitations of each
      imaging modality described, including optic disk photography, confocal scanning
      laser ophthalmoscopy (CSLO) and optical coherence tomography (OCT). These
      modalities provide en face and/or cross-sectional images of the LC in vivo.
      Enhanced depth imaging OCT has recently led to important advances in imaging
      deeper structures of the posterior segment, including the LC. Adaptive optics has
      been adopted in CSLO and OCT imaging to correct for ocular aberration and has
      improved resolution and contrast of the LC images. Post-image processing
      techniques to compensate for light attenuation and enhance contrast in OCT images
      enabled better visualization of the LC beneath the neuroretinal rim, vascular
      structures, and scleral rim. Long-wavelength probe OCT has shown good
      visualization of the LC with improved penetration when combined with swept-source
      OCT. Contrast agents for enhanced visualization of selective target structures in
      OCT have been developed. All these technologies hold great promise for improved
      in vivo imaging of the LC and require further investigation. 

PMID- 23960951
TI  - The profile of glaucoma in a Tertiary Ophthalmic University Center in Riyadh,
      Saudi Arabia.
AB  - PURPOSE: To report the pattern of glaucoma among Saudi patients who were
      presented to King Abdul Aziz University Hospital (KAUH). METHODS: All glaucoma or
      glaucoma suspect patients who were presented to KAUH from 2006 to 2008 were
      included; medical files of all patients were retrieved and evaluated through
      standardized international guidelines. Collected data included: age, sex,
      laterality, intraocular pressure, and cup/disk ratio. Prevalence of different
      glaucoma types (including 95% CI) was calculated, ANOVA and post hoc tests were
      applied to evaluate the difference in indices across different types. RESULTS: A
      total of 2296 eyes of 1236 patients were included. Primary angle closure glaucoma
      (PACG) was the predominant type (46.6%) followed by primary angle closure (PAC)
      (17.2%), then primary open angle glaucoma (POAG) (12.8%), and secondary glaucoma
      (13%). Other types including (normal tension glaucoma (5.9%), childhood glaucoma
      (2.6%), and juvenile glaucoma (1.9%)) were also present but of lower prevalence.
      CONCLUSION: Primary angle closure glaucoma was the predominant form of glaucoma
      followed by PAC, and POAG suggesting that the pattern in Saudi Arabia could be
      quite different from that reported for primary glaucomas in the Western
      literature. In addition, pseudoexfoliation was the most common form of secondary
      open and closed angle glaucoma. These results indicate the need for a national
      intervention program for early detection and referral of glaucoma cases in order
      to prevent significant visual loss. There is also a need for a community based
      assessment to determine the prevalence of glaucoma as a baseline for future
      intervention.

PMID- 23960952
TI  - The disc as the basis of treatment for glaucoma.
AB  - The goal of the treatment of patients with glaucoma is to prevent disability or,
      if disability already exists, to repair the disability or at the least to prevent
      further disability from developing. To achieve these goals requires knowing what
      will happen if there is no treatment and what will happen if there is treatment.
      That is, one must know the possible benefits from the therapy in comparison to
      the damage caused by the therapy. As we will demonstrate, the classic risk
      factors do not provide accurate estimates of the development of disability and do
      not answer these two questions. The most helpful clues are provided by what the
      patient says, by whether the disc is damaged and by whether the disc is
      deteriorating. The severity of disease is best estimated by the nature of the
      optic disc and how it changes. This report is primarily focused on increasing the
      skill of the physician in being able to estimate the nature of the optic disc and
      how that changes. This does not, however, lessen the tremendous importance of
      careful history-taking and of gonioscopy. In this report, however, we focus on
      the evaluation of the disc. Currently disc evaluation is often not adequate
      because of poor examination techniques, reliance on cup/disc ratios, and reliance
      on the results of image analyzers. We will present here the Disc Damage
      Likelihood Scale, which is a user-friendly method which correlates accurately
      with visual field changes. 

PMID- 23960953
TI  - Antiglaucoma drugs: The role of preservative-free formulations.
AB  - Hypersensitive reactions to eyedrops are a common finding in clinical practice
      and represent a frequent cause of discontinuation of the therapy. Moreover,
      experimental and clinical studies show that long term use of topical drugs may
      induce ocular surface changes causing discomfort and potentially negatively
      affecting the compliance to the treatment as well as the success rate of
      filtering procedures. The exact mechanism involved and the roles of the active
      compound and the preservatives in inducing such detrimental effects of ophthalmic
      solutions are unclear. During the last years several antiglaucoma agents have
      been marketed as either preservative-free or benzalkonium chloride-free
      formulations in an attempt to reduce the adverse effects related to
      preservatives. This paper summarizes the body of evidence from existing studies
      about preservatives in antiglaucoma eyedrops, focusing on the latest compounds
      commercially available. A systematic review of the literature was performed.
      Current research is focusing not only on the efficacy of the drugs but also on
      their tolerability. Based on the existing data, there is a rationale to support
      the use of benzalkonium-free solutions whenever possible, especially in patients
      suffering from concomitant ocular surface diseases, experiencing local side
      effects and in those expected to need multiple and prolonged topical treatments. 

PMID- 23960954
TI  - Mitochondrial DNA abnormalities in ophthalmological disease.
AB  - Mitochondrial disorders are a group of clinically heterogeneous diseases,
      commonly defined by lack of cellular energy due to genetic defects of oxidative
      phosphorylation (OXPHOS). Ocular involvement is a prominent clinical feature of
      mitochondrial disease. This can manifest as optic nerve dysfunction specifically
      involving retinal ganglion cells as typified by Leber hereditary optic neuropathy
      (LHON), or progressive external ophthalmoplegia (PEO) and ptosis involving the
      extraocular muscles which is commonly associated with either primary
      mitochondrial DNA (mtDNA) mutations or acquired mtDNA defects secondary to a
      nuclear genetic disorder of mtDNA maintenance. In this short review, we will
      outline the unique characteristics of mitochondrial genetic disease and its
      investigation with reference to the clinical features and molecular genetic
      abnormalities underlying mitochondrial ophthalmological disease. 

PMID- 23960955
TI  - Unilateral amblyopia: Optical coherence tomography findings.
AB  - PURPOSE: This study was performed to measure the macular and the retinal nerve
      fiber layer (RNFL) thicknesses using optical coherence tomography (OCT) in
      patients with unilateral amblyopia. METHODS: Measurement of the Retinal nerve
      fiber layer and Macular Retinal Layer thickness for both amblyopic and normal
      fellow eyes by (OCT) was carried out at king Abdulaziz University Hospital,
      Riyadh, Saudi Arabia. RESULTS: Ninety-three patients with unilateral amblyopia
      between the ages of 5 years and 12 years were included. The macular retinal
      thickness and the RNFL thickness were measured using OCT. The mean macular
      retinal thickness was 259.3 MUm and 255.6 MUm, and the mean RNFL thickness was
      112.16 MUm and 106 MUm, in the amblyopic eye and the normal eye, respectively.
      OCT assessment of RNFL thickness revealed a significantly thicker RNFL in
      amblyopic eye (P < 0.0001), but no statistically significant difference was found
      in macular retinal thickness (P = 0.195). CONCLUSION: The amblyopic process may
      involve the RNFL, but not the macula. However, further evaluation is needed.

PMID- 23960956
TI  - The recurrence of pterygium after different modalities of surgical treatment.
AB  - PURPOSE: To assess and compare the recurrence rate of pterygium after limbal stem
      cell transplantation versus amniotic membrane transplantation (AMT) as ocular
      surface reconstructing measures in recurrent pterygium, also evaluation of the
      use of antimetabolite drugs as adjunctive therapy for AMT. PATIENTS AND METHODS:
      Prospective randomized comparative study included 60 eyes of 48 patients with
      recurrent pterygia. Informed consents were taken from all patients. Primary
      pterygium excision was performed 6-15 months ago; the cases were divided randomly
      into three equal groups: Group 1: included 20 eyes with excision of the pterygium
      and application of limbal stem cell transplantation with conjunctival autograft,
      group 2: included 20 eyes with excision of the pterygium followed by AMT and
      group 3: included 20 eyes in which surgical excision of pterygium was followed by
      intra-operative application of low-dose of MMC (0.05%) for 3 min then using AMT.
      RESULTS: The study included 36 males and 12 females of age ranged from 28 to 52
      years. The recurrence rate was 2 eyes in group 1 (10%) (limbal stem cell
      transplantation + conjunctival autograft), 6 eyes in group 2 (30%) (AMT) and 4
      eyes (20%) in group 3 (MMC + AMT). The rate of recurrence was significantly
      different between the three groups (P < 0.001). CONCLUSIONS: Limbal stem cell
      transplantation together with conjunctival autografting proved to be more
      effective in prevention of pterygium recurrence and in rapid restoration of
      normal epithelial morphology. MMC in addition to AMT decreases the incidence of
      recurrence.

PMID- 23960957
TI  - The distinguishing anthropometric features of the Saudi Arabian eyes.
AB  - PURPOSE: Identifying the peri-ocular anthropometric measurements characteristic
      of Saudi Arabian eyes. METHODS: A prospective, cohort, hospital-based study.
      RESULTS: Measurements were made on 668 subjects (mean age 33.8 years; 58.7%
      female). The horizontal palpebral aperture was 30.1 +/- 2.9 mm (mean +/- SD),
      vertical palpebral aperture was 10.1 +/- 0.85 mm, upper lid skin fold height was
      3.6 +/- 1.9 mm, upper lid crease height was 9.6 +/- 0.8 mm, eyebrow height was
      10.2 +/- 2.7 mm, and intercanthal distance was 32 +/- 2.7 mm. There was a
      statistically significant correlation between gender and eyebrow height (P =
      0.001) and gender and horizontal palpebral aperture (P = 0.016), but no
      significant correlations were noted between any measurement and age. CONCLUSIONS:
      Saudi Arabian eyes are unique in exhibiting a higher upper lid skin fold, higher
      lid crease.

PMID- 23960958
TI  - Airbag induced facial and bilateral ocular injuries in a 14-year-old child.
AB  - Although air bags have reduced the incidence of fatal and severe injuries in
      automobile collisions, they have been shown to carry a risk of injury themselves.
      Ocular injury in particular can often be a direct consequence of air bag
      deployment. We report a 14-year-old child who sustained facial burn and bilateral
      ocular injuries affecting both the anterior and posterior segments due to an
      inflated air bag in a low speed motor vehicle accident. 

PMID- 23960959
TI  - Symptomatic osteoma originated from lamina papyracea.
AB  - We describe a 74-year-old woman with osteoma of the lamina papyracea who only
      presented with 4-month history of an unspecific compression and pain in the
      medial canthal area of the left eye. The patient reported prompt relief from her
      pain after resection of the osteoma by endoscopic sinus surgery and she was free
      of pain clinically with no evidence of recurrence at 12 months followup. Also, we
      reviewed the literature relevant to the pathophysiology of the osteoma pain. 

PMID- 23960960
TI  - Cataract update.

PMID- 23960961
TI  - Childhood cataract in sub-Saharan Africa.
AB  - Investment by organizations and agencies has led to a growing body of evidence
      and information to assist ophthalmologists and others to meet the needs of
      children with cataract in Africa. The geographic distribution of research,
      training, and programme development across Africa has been uneven; investment has
      been greatest in eastern and southern Africa. Population based surveys (using key
      informants) suggest that 15-35% of childhood blindness is due to congenital or
      developmental cataract. There may be up to 82,000 children with non-traumatic
      cataract in Africa, with approximately 19,000 new cases each year. Effective
      strategies to find and refer children are those that engage the community in case
      detection. Identification and referral does not automatically mean surgical
      intervention with distance to the surgical facility being the most common reason
      for failure to seek care. Surgical management has become more specialized and a
      team based approach has been adopted by many paediatric ophthalmologists and
      their programmes. Although many children still present late for surgery, outcomes
      of surgery are much improved from previous experiences. Research suggests that
      post-operative follow up, still a challenge, can be improved through adoption of
      specific strategies. There has been limited success in ensuring that children are
      placed in appropriate educational settings. While eye care professionals may feel
      their responsibility ends with clinical care, it is important for the paediatric
      eye care team to be engaged with educational and rehabilitation services. 

PMID- 23960962
TI  - Challenges and approaches in modern biometry and IOL calculation.
AB  - The introduction of new intraocular lenses (IOLs), industry marketing to the
      public and patient expectations has warranted increased accuracy of IOL power
      calculations. Toric IOLs, multifocal IOLs, aspheric IOLs, phakic lenses,
      accommodative lenses, cases of refractive lens exchange and eyes that have
      undergone previous refractive surgery all require improved clinical measurements
      and IOL prediction formulas. Hence, measurement techniques and IOL calculation
      formulas are essential factors that affect the refractive outcome. Measurement
      with ultrasound has been the historic standard for measurement of ocular
      parameters for IOL calculation. However the introduction of optical biometry
      using partial coherence interferometry (PCI) has steadily established itself as
      the new standard. Additionally, modern optical instruments such as Scheimpflug
      cameras and optical coherence tomographers are being used to determine corneal
      power that was normally the purview of manual keratometry and topography. A
      number of methods are available to determine the IOL power including the
      empirical, analytical, numerical or combined methods. Ray tracing techniques or
      paraxial approximation by matrix methods or classical analytical 'IOL formulas'
      are actively used in for the prediction of IOL power. There is no universal
      formula for all cases - phakic and pseudophakic cases require different
      approaches, as do short eyes, long eyes, astigmatic eyes or post-refractive
      surgery eyes. Invariably, IOLs are characterized by different methods and lens
      constants, which require individual optimization. This review describes the
      current methods for biometry and IOL calculation. 

PMID- 23960963
TI  - Axial length measurement techniques in pediatric eyes with cataract.
AB  - Globe axial length (AL) in children is commonly measured using either contact or
      immersion technique. Office measurement of AL can be difficult in young children
      and infants and must often be done under anesthesia in an eye that is unable to
      cooperate with precise fixation and centration. Contact A-scan measurements yield
      shorter AL, on average, than immersion A-scan measurements in pediatric eyes.
      This difference is mainly the result of the anterior chamber depth rather than
      the lens thickness value. During intraocular lens power calculation, if globe
      axial length is measured by the contact technique, it will result in the use of
      an average 1-D stronger IOL power than is actually required. This can lead to
      induced myopia in the postoperative refraction. In our studied patients, there
      was a significant difference in prediction error between contact A-scan biometry
      and immersion A-scan biometry. The immersion A-scan technique is recommended for
      pediatric IOL power calculation. We also provide a review of biometry in
      pediatric eyes. The overall mean AL of pediatric cataractous eyes is
      significantly different than the mean AL of non cataractous eyes. More
      importantly, the standard deviation is higher in eyes with cataract than in those
      without. Three phases of eye growth in children have been documented: A rapid,
      postnatal phase from birth to 6 months of age, followed by a slower, infantile
      phase from 6 to 18 months of age, and finally a slow, juvenile phase from 18
      months forward. In our study, girls had shorter ALs than boys and African
      American subjects had longer ALs than Caucasians. Eyes with unilateral cataract
      had shorter ALs than eyes with bilateral cataract during the earlier years, but
      had longer ALs during later childhood. 

PMID- 23960964
TI  - Intraocular lens power calculation after myopic and hyperopic laser vision
      correction using optical coherence tomography.
AB  - PURPOSE: To use optical coherence tomography (OCT) to measure corneal power and
      calculate intraocular lens (IOL) power in cataract surgeries after myopic and
      hyperopic laser vision correction (LVC). METHODS: Patients with previous LVC were
      enrolled in this prospective study at two centers (Doheny Eye Institute, Los
      Angeles, CA, USA and Cullen Eye Institute, Houston, TX, USA). Corneal power was
      measured with a Fourier-domain OCT system. The intravisit repeatability of OCT
      corneal power measurement was evaluated by the pooled standard deviation of
      repeat scans. Axial length, anterior chamber depth, and automated keratometry
      were measured with the IOLMaster. An OCT-based IOL formula was developed. The
      mean absolute error (MAE) of refractive prediction for OCT-based IOL formula was
      calculated. The results were compared with the MAE for Haigis-L formula. RESULTS:
      A total of 31 eyes of 24 subjects who had uncomplicated cataract surgery with
      monofocal IOL implantation were enrolled in the two sites. Twenty-two eyes of 16
      subjects had previous myopic LVC that ranged from -12.46 D to -0.88 D. Nine eyes
      of 8 subjects had previous hyperopic LVC that ranged from 0.66 D to 5.52 D. The
      intravisit repeatability of OCT corneal power measurement was 0.24 D. For the
      myopic LVC group, the OCT formula had a MAE of 0.57 D compared to an MAE of 0.73
      D for the Haigis-L formula (p = 0.19). For the hyperopic LVC group, the MAE for
      OCT and Haigis-L formula was 0.26 D and 0.54 D, respectively (p > 0.05).
      CONCLUSIONS: Corneal power can be precisely measured with OCT. The predictive
      accuracy of OCT-based IOL power calculation is equal to current standards for
      post-LVC eyes.

PMID- 23960965
TI  - Clinical applications of Scheimpflug imaging in cataract surgery.
AB  - Since the Scheimpflug principle was first described over a century ago, there has
      been a great interest among ophthalmologists for the use of Scheimpflug camera in
      anterior segment imaging. Scheimpflug imaging has since advanced significantly
      and modern day instruments provide comprehensive imaging and topographic data of
      the anterior segment. In this article the clinical applications and limitations
      of Scheimpflug imaging in modern cataract surgery patients are discussed. This
      article reviews recent work on assessment of lens transparency for cataract
      grading and integrity, using preoperative lens density measurements to help
      predict phacoemulsification parameters, its utility in challenging situations
      like capsular bag distension syndrome and traumatic cataract and assessment of
      density of the posterior capsule for objectively quantifying posterior-capsule
      opacification. 

PMID- 23960966
TI  - Capsulorhexis: Pearls and pitfalls.
AB  - A critical step in phacoemulsification (as well as extracapsular cataract
      extraction) is making a window in anterior capsule wall (i.e. anterior
      capsulotomy). Continuous Curvilinear Capsulorhexis (CCC) has become recognized as
      the standard method of anterior capsulectomy. Techniques employed for CCC have
      undergone sustained evolution. The present review evaluates elementary principles
      of CCC. Management of CCC in the presence of small pupil and pseudoexfoliation
      syndrome is discussed. Main differences of pediatric CCC from its adult-style
      counterpart and finally several techniques of rescue of an extending
      capsulorhexis are also reviewed. 

PMID- 23960967
TI  - Posterior polar cataract: A review.
AB  - Posterior polar cataract is a rare form of congenital cataract. It is usually
      inherited as an autosomal dominant disease, yet it can be sporadic. Five genes
      have been attributed to the formation of this disease. It is highly associated
      with complications during surgery, such as posterior capsule rupture and nucleus
      drop. The reason for this high complication rate is the strong adherence of the
      opacity to the weak posterior capsule. Different surgical strategies were
      described for the handling of this challenging entity, most of which emphasized
      the need for gentle maneuvering in dealing with these cases. It has a unique
      clinical appearance that should not be missed in order to anticipate, avoid, and
      minimize the impact of the complications associated with it. 

PMID- 23960968
TI  - Approaches to a posterior polar cataract.
AB  - Posterior polar cataracts present special challenges to the cataract surgeon.
      These are often associated with weakness/dehiscence of the posterior capsule and
      thus have a higher rate of intraoperative posterior capsule rupture. The surgeon
      needs to adhere to special surgical strategies to minimize the risk of a
      posterior capsule rupture. These include, adhering to the principles of closed
      chamber technique, avoiding hydrodissection - instead performing 'inside-out'
      hydrodelineation and using modest to low phaco parameters and reducing these
      stepwise. This article provides important pearls on how to approach a posterior
      polar cataract. 

PMID- 23960969
TI  - Cataract surgery in patients with history of uveitis.
AB  - Cataract surgery in patients with uveitis is not as simple as any senile cataract
      surgery. Recent evidence suggests that useful visual outcome can be achieved in
      most of the cases if they are handled meticulously. Key factors leading to
      improved visual outcome are absolute control of preoperative inflammation with
      diligent use of immunomodulatory drugs, meticulous surgery along with early
      detection and care of postoperative complications. Modern technologies in the
      intraocular lens designs and materials have contributed to the success. In this
      article, we review the literature on this subject with emphasis on the importance
      of the use of immunomodulatory drugs to control preoperative and postoperative
      intraocular inflammation and avoid complications. 

PMID- 23960970
TI  - Spontaneous dislocation of posterior chamber intraocular lenses (PC IOLs) in
      patients with retinitis pigmentosa - Case series.
AB  - PURPOSE: To report the outcomes of intraocular lens (IOL) dislocation management
      in 6 cases with Retinitis Pigmentosa (RP). SETTING: Private practice, Los
      Angeles, USA. DESIGN: Retrospective interventional case series. METHODS: The
      medical reports of six eyes of four RP patients with capsule bag fixated
      posterior chamber IOL dislocation were retrospectively reviewed. Pre-operative
      data included demographics, systemic or ocular disorders, history of trauma,
      previous intraocular surgery and pre-operative visual acuity. Outcome measures
      included the type of surgery, surgical complications, elevation of intraocular
      pressure (IOP), ocular inflammation, cystoid macular edema (CME) and IOL
      dislocation at 3 months or greater post-operatively. RESULTS: The medical records
      of six eyes of four patients operated on between December 2009 and May 2011 were
      evaluated. In four cases, dislocated PC IOL implants were sutured to the sclera.
      In two eyes of one patient anterior chamber IOLs (AC IOLs) were implanted after
      PC IOLs were explanted. One eye developed CME during the follow-up period.
      Despite modest tilt in one case and modest decentration in another, stability and
      centration of the IOLs was excellent during the follow-up period. No eyes had
      intraocular inflammation requiring long term medical treatment, new onset
      glaucoma or retinal detachment. Mean follow-up time was 6.9 months (range 3-20).
      CONCLUSIONS: Cataract surgeons should be aware of the increased risk for
      decentration and malposition of PC IOLs in patients with RP. Satisfactory results
      can be achieved by fixation of the PC IOL or AC IOL implantation.

PMID- 23960971
TI  - Hereditary pediatric cataract on the Arabian Peninsula.
AB  - Hereditary pediatric cataract on the Arabian Peninsula does not follow the same
      epidemiological patterns as described for Western populations. This article
      describes selected genetic causes for inherited pediatric cataract in the region.

PMID- 23960972
TI  - Femtosecond cataract surgery: A review of current literature and the experience
      from an initial installation.
AB  - Cataract surgery remains the most widely performed intraocular procedure
      throughout the world. Safety and accuracy of the procedure are paramount and
      techniques should remain under constant review. Recently, the introduction of the
      femtosecond laser to assist cataract surgery has provided ophthalmologists with
      an exciting tool that may further improve outcomes. We review the existing
      literature and discuss the installation and initial experience of a femtosecond
      laser into our practice. 

PMID- 23960973
TI  - Histopathological findings of failed grafts following Descemet's stripping
      automated endothelial keratoplasty (DSAEK).
AB  - PURPOSE: To study the histopathological findings of the early cases of failed
      DSAEK grafts and to analyze the causes of graft failure. METHODS: Retrospective
      study of 13 failed DSAEK grafts (four grafts submitted alone with no host cornea)
      of 12 patients. The histopathologic features are correlated with the clinical and
      operative findings. RESULTS: Significant attenuation of the endothelial cells
      found in 10/13 cases (77%), retained recipient Descemet's membrane in 7/13 (54%),
      variability of graft thickness in 5/13 (38%) and two of these had stromal
      irregularity. Retrocorneal fibrous membrane along the donor's Descemet's membrane
      was found in 4/13 (31%) resulting in endothelial detachment in one case. Eight of
      the nine host cornea-graft specimens were found to have: total graft-cornea
      detachment (in one), subtotal in four and partial (?50% of graft length) in
      three. The detached flaps showed infection at the interface of the graft-host
      cornea in two, epithelial ingrowth and fibrous proliferation along the anterior
      stromal surface of the graft (one case each). An additional histopathological
      finding was secondary amyloid deposition within the host stroma (in one).
      CONCLUSION: Irregular or thick graft, graft-host interface fibrous/epithelial
      ingrowth, and infection all predispose to DSAEK failures related to graft
      detachment. Endothelial cells attenuation and retrocorneal fibrous membrane are
      major causes for primary graft failure.

PMID- 23960974
TI  - Percaruncular single injection peribulbar anaesthesia in patients with axial
      myopia for phacoemulsification.
AB  - BACKGROUND: Myopia has been identified as a risk factor for globe perforation
      during regional anaesthesia for cataract surgery. We conducted this study to
      evaluate efficacy of single injection percaruncular peribulbar anaesthesia for
      phacoemulsification in patients with axial myopia. METHODS: Eighty patients with
      axial myopia received percaruncular peribulbar anaesthesia and were evaluated for
      incidence of major or minor complications. Also surgeon and patients'
      satisfaction and their comment on operative conditions were noted. RESULTS: Of
      the 80 patients 51 patients had posterior staphylomas. About three quarters of
      the patients developed adequate akinesia in 10 min. Remaining 25% received second
      injection with the same technique but with less volume after which the percent of
      patients with adequate akinesia rose to 91%. Adequate analgesia developed in
      almost all patients and only in one patient, intravenous analgesia was necessary
      to complete the operation. All operations were completed uneventfully. No
      perforations or penetrations were recorded and no other major complications were
      encountered. About 97% of the surgeons and 96% of the patients found the
      operative conditions satisfactory. CONCLUSION: Using single injection
      percaruncular peribulbar local anaesthesia for phacoemulsification in patients
      with axial myopia is an effective technique.

PMID- 23960975
TI  - Electrophysiological study of myopia.
AB  - PURPOSE: To investigate the characteristics of retinal function in myopia using
      full-field electroretinogram (ERG) and multifocal ERG (MF-ERG) and to determine
      the correlation among MF-ERG, ocular axis length, retinal thickness and degree of
      myopia. METHODS: Twenty emmetropes (20) and sixty-eight myopes (68) underwent
      manifest refraction, A- and B-scan, fundus examination, fluorescein angiography
      (FA), optical coherence tomography (OCT), full field ERG and MF-ERG. The
      amplitudes and implicit times of ERG were determined. The results were further
      analyzed by comparing ocular axis length, refraction, retinal thickness, and
      macular function detected by ERG parameters. RESULTS: There was a significant
      difference in implicit times of MF-ERG of an emmetrope and a moderate and high
      myopia whereas implicit times of mild myopia patients and emmetropes were
      similar. There was a statistically significant difference in amplitude densities
      of first positive peak of MF-ERG P1 wave between an emmetrope and a moderate and
      high myopia. In central ring and four quadrants, amplitude densities showed
      negative correlation to ocular axis length and diopter of myopia. There was no
      statistically significant difference between the average retinal thickness in
      emmetropic and physiological myopic eyes (low, medium, high), but there was
      significant difference between physiological and pathological myopia. CONCLUSION:
      Decreased foveal function as determined by MF-ERG is associated with high degree
      of myopia. Retinal function impairment is correlated with increase in the diopter
      of myopia, decrease of corrected visual acuity (VA), elongation of ocular axis
      and increased macular degeneration.

PMID- 23960976
TI  - Effect of anterior capsular polishing on the rate of posterior capsule
      opacification: A retrospective analytical study.
AB  - AIM: To determine whether anterior capsule polishing during cataract surgery done
      by phacoemulsification has any effect on the rate of posterior capsule
      opacification. MATERIALS AND METHODS: We conducted a 3 year retrospective
      analytical study at our hospital. The medical records of patients who underwent
      cataract extraction by phacoemulsification with foldable square edge hydrophilic
      PCIOL between April 2007 and March 2010 were reviewed. The study included 1009
      eyes of 950 patients who underwent phacoemulsification with foldable square edge
      hydrophilic IOL in the bag implantation with anterior capsular polishing. The
      control group included 981 eyes of 957 patients in whom anterior capsular
      polishing was not done. Patients in the age group of 45-65 years with well
      dilating pupils were included in the study. They were evaluated at 1 week, 1
      month and 1 year post-operatively. Exclusion criteria included glaucoma, shallow
      anterior chamber, uveitis, high myopia, pseudoexfoliation, diabetes mellitus,
      traumatic cataracts, posterior polar cataract, subluxated cataracts, previous
      ocular surgeries, patients allergic to dilating drops, and steroid intake.
      Intraoperatively, the exclusion criteria were not achieving the total anterior
      capsule cover on the IOL optic, sulcus fixated IOL, and any intraoperative
      complications like posterior capsule rupture. After bimanual
      irrigation/aspiration, all enrolled patients were randomly assigned to receive
      either 360 degree anterior capsular polishing or No anterior capsular polishing
      and results were studied. RESULTS: The rate of posterior capsule opacification in
      the study group and in the control group was not statistically significant.
      CONCLUSION: Though it was thought that anterior capsular polishing will lead to
      reduced rate of PCO formation, our study showed that there was no significant
      difference in PCO formation between the two groups. However, it was seen that the
      rate of anterior capsule opacification and capsular phimosis showed a significant
      reduction in cases in which anterior capsular polishing was done.

PMID- 23960977
TI  - Polymethyl methacrylate intraocular lens opacification 20 years after cataract
      surgery: A case report in a tertiary eye hospital in Saudi Arabia.
AB  - Snowflake degeneration is a slow progressive opacification of polymethyl
      methacrylate (PMMA) intraocular lenses (IOLs). This late postoperative
      complication can occur a decade or later after implantation. The deposits are
      composed of IOL materials that tend to aggregate centrally. There is a relative
      paucity of the literature on snowflake degeneration of IOLs. Symptoms can range
      from mild visual disturbance to significant loss of visual acuity. In cases of
      opacification after IOL implantation, the different diagnosis should include
      snowflake degeneration to prevent surgical intervention such as lens exchange or
      explantation unless clinically warranted. We report a case of late optical
      opacification of a PMMA IOL, the clinical diagnosis and treatment that increased
      best corrected vision. 

PMID- 23960978
TI  - Pigment deposits on hydrophilic intraocular lenses after phacoemulsification
      cataract surgery.
AB  - A heterogeneous group of conditions can cause changes to the intraocular lens
      (IOL) during or after implantation in uneventful cataract surgery. We describe a
      series of 5 patients presenting distinctive deposits on the surface of
      hydrophilic intraocular lenses, implanted during routine cataract surgery, with a
      follow-up of 1 to 24 months. Disposable forceps were found to be the source of
      the pigmented marks when used to hold the lens during the injector loading
      process. At the slit-lamp examination, the pigments were located in the centre of
      the lens optic, easily detectable. Although involving the visual axis, none of
      the patients were visually affected. To our knowledge, this is the first time
      such unusual occurrence has been described. The reported case-series shows the
      importance of in-house follow-up after cataract surgery. 

PMID- 23960980
TI  - [Not Available].

PMID- 23960979
TI  - To avoid post-operative refractive error in cataract surgery.
AB  - One of the greatest issues facing the cataract surgeon today is accurate
      prediction of post-operative refractive error. With use of intraoperative
      autorefractometry (IOAR), such errors can be detected and post-operative
      refractive errors avoided. An 83-year-old woman was admitted for right eye
      phacoemulsification, with aimed at -1.78D with Sanders/Retzlaff/Kraff/T (SRK/T)
      formula implantation under local anesthesia. IOAR was performed after IOL
      insertion. The first estimate was +1.1D, indicating hyperopia, and far from the
      desired refraction above 2D. IOL exchange to +11.5D was, therefore, performed.
      The second estimate was -0.13D and the operation was completed. The final
      refraction (3 years after operation) was -0.25D. With IOAR, we were able to avoid
      the unpleasant surprise of a mistaken intraocular lens power. Intraoperative
      autorefractometry is useful for avoiding errors in IOL power. 

PMID- 23960981
TI  - Fine needle aspiration biopsy of ophthalmic tumors.
AB  - A majority of intraocular tumors can be diagnosed based on clinical examination
      and ocular imaging studies, which obviate the need for diagnostic ophthalmic fine
      needle aspiration biopsy (FNAB). Overall, diagnostic accuracy of ophthalmic FNAB
      is high but limited cellularity can compromise the diagnostic potential of
      ophthalmic aspirate samples. The role of ophthalmic FNAB is limited in retinal
      tumors. Orbital FNAB should be considered in the evaluation of lacrimal gland
      tumors, orbital metastasis, and lymphoproliferative lesions. Negative cytologic
      diagnosis of malignancy should not be considered unequivocal proof that an
      intraocular malignancy does not exist. With improved understanding of genetic
      prognostic factors of uveal melanoma, ophthalmic FNAB is gaining popularity for
      prognostic purposes in combination with eye conserving treatment of the primary
      tumor. In special clinical indications, ancillary studies such as
      immunohistochemistry and FISH can be performed on ophthalmic FNAB samples.
      Assistance of an experienced cytopathologist cannot be overemphasized. 

PMID- 23960982
TI  - Transitional neoplasms of the naso-lacrimal system: A review of the
      histopathology and histogenesis.
AB  - Transitional papilloma (inverted papilloma, Schneiderian papilloma) is a
      relatively common, benign epithelial neoplasm of the sinonasal tract that also
      occurs in the lacrimal drainage system. The name transitional papilloma is
      recommended because it reflects the key histological features required for
      pathological diagnosis, as well as the histogenesis of the tumour. The
      histogenesis of the tumour is reviewed, together with its natural history, which
      is characterized by bone remodelling and destruction, a tendency to recur and to
      undergo malignant transformation. Biomarkers associated with these features have
      been identified in the sinonasal tumours and may also be of relevance to the
      lacrimal sac tumours, although the necessary studies have not yet been
      undertaken. 

PMID- 23960983
TI  - Update on lacrimal gland neoplasms: Molecular pathology of interest.
AB  - Lacrimal gland neoplasms are rare and much of our knowledge of the behavior and
      molecular pathogenesis of these tumors comes from study of the similar, but more
      numerous salivary gland neoplasms. After briefly discussing the classification of
      lacrimal gland neoplasms, I review three areas of emerging knowledge in the
      pathogenesis of these neoplasms: (1) the concept of adenoid cystic carcinoma with
      high-grade transformation and the associated cytogenetic changes; (2) recent
      analysis of the MYB-NFIB gene fusion in adenoid cystic carcinoma, and; (3)
      overexpression of HER2 in malignant salivary and lacrimal neoplasms. 

PMID- 23960984
TI  - Ocular melanoma.
AB  - Ocular melanomas comprise uveal and conjunctival sub-types, which are very
      different from each other. A large majority of uveal melanomas involve the
      choroid, with less than 10% being confined to the ciliary body and iris. They
      tend to metastasize haematogenously, almost always involving the liver.
      Therapeutic methods include various forms of radiotherapy, surgical resection and
      phototherapy, which are often used in combination. Conjunctival melanomas show
      many similarities to their cutaneous counterparts, often metastasizing by
      lymphatic spread. Treatment consists of excision of invasive melanoma with
      adjunctive radiotherapy and/or cryotherapy and topical chemotherapy for intra
      epithelial disease. The management of patients with ocular melanomas demands a
      good understanding of the pathology of these tumours. Pathological examination of
      the tumour indicates the prognosis and hence the need for further investigation
      and treatment. The scope of the pathologist is enhanced thanks to advances in
      molecular biology. 

PMID- 23960985
TI  - Uveal melanoma: Ocular and systemic disease.
AB  - Although rare, uveal melanoma is the most common intraocular tumor in adults.
      Most cases arise from the choroidal layer of the uvea, displaying a discoid,
      collar-button, or mushroom shaped growth. Histopathologically, neoplasms are
      classified by the dominant cell type: spindle, epithelioid or mixed spindle cell
      type. The most important prognostic factors are cell type, nucleolar size,
      largest tumor dimension, and mitotic figures. Patient prognosis is poor when
      metastases occur in the liver, one of the main reasons that despite advances in
      the diagnosis and treatment of uveal melanoma, the mortality rate has not change
      significantly since 1973. 

PMID- 23960986
TI  - Conjunctival malignant melanoma: A rare variant and review of important
      diagnostic and therapeutic considerations.
AB  - Malignant melanoma of the conjunctiva is a relatively infrequent neoplasm that
      can be associated with significant morbidity and cause diagnostic difficulty to
      both the ophthalmologist and pathologist. We herein describe the first reported
      case in North American and European databases of a rare variant-signet ring cell
      melanoma - arising in the background of primary acquired melanosis (PAM) and use
      this case as a review of important diagnostic and therapeutic considerations when
      faced with this condition. 

PMID- 23960987
TI  - "Retinoblastoma survival disparity": The expanding horizon in developing
      countries.
AB  - The patients' survival for the most common intraocular tumor in children,
      retinoblastoma, has a wide spectrum among the world countries. This study was
      conducted to provide an overview of the retinoblastoma survival disparity
      worldwide by discussing the trends of patients' survival, as well as recent
      advances in the management of retinoblastoma. The design of this study was
      literature review and commentary. Selected articles from PubMed (except one)
      including both developing and developed countries regarding the patients'
      survival in retinoblastoma were considered and reviewed critically. An analysis
      of 47 articles was performed. In conclusion, in spite of an obvious contrast of
      retinoblastoma survival disparity in the world, the expanding horizons in
      developing countries are promising and continuing on all fronts and results are
      hope-inspiring. 

PMID- 23960988
TI  - Retinoblastoma major review with updates on Middle East management protocols.
AB  - Many advances in the field of management of retinoblastoma emerged in the past
      few years. Patterns of presentation of retinoblastoma in the Middle East region
      differ from Western community. The use of enucleation as a radical method of
      eradicating advanced disease is not easily accepted by patient's family. We still
      do see stage E, failed or resistant retinoblastoma and advanced extraocular
      disease ensues as a result of delayed enucleation decision. In this review, we
      discuss updates in management of retinoblastoma with its implication on patients
      in our part of the world. Identifying clinical and high risk characteristics is
      important prognostically and are discussed for further management of
      retinoblastoma cases. 

PMID- 23960989
TI  - Orofacial granulomatosis presenting as bilateral eyelid swelling.
AB  - Orofacial granulomatosis (OFG) is an uncommon but increasingly recognized disease
      of unknown etiology. The typical presentation is chronic swelling of the perioral
      soft tissue, but eyelid edema can be the sole manifestation. Terminology of this
      disease can be confusing as it may also be referred to as granulomatous cheilitis
      and a monosymptomatic presentation of Melkersson-Rosenthal syndrome (MRS).
      Crohn's disease and sarcoidosis should also be considered in the differential as
      the histopathology can be similar. Corticosteroids are the mainstay of treatment
      but can lack efficacy. Atypical presentations and the possibility of systemic
      disease involvement can further challenge the management. We describe an unusual
      case in which OFG manifests solely as chronic eyelid swelling. This 69-year old
      Asian female patient had a delayed diagnosis that responded well to intralesional
      corticosteroid injection with surgical skin reduction. In addition to describing
      this unusual presentation of OFG, we review the relevant literature and evaluate
      the current terminology used to describe this entity. 

PMID- 23960990
TI  - Endophthalmitis: A review of recent trends.
AB  - Endophthalmitis is a feared complication of trauma, surgical procedures and
      septicemia. Although uncommon, its potential for significant visual loss is well
      recognized. Especially over the past decade, complicated surgeries and medical
      techniques have increased and seriously ill patients are being sustained in ever
      increasing numbers. New pathogens are being recognized and known ones
      reclassified thanks to advances in molecular analysis. Continuously evolving PCR
      methodologies also add a new dimension to the diagnosis of infectious
      endophthalmitis. As well, medical literature is now truly international,
      encompassing studies from around the world that expand our understanding of
      ocular infectious disease. This report reviews some of these changes as they
      relate to endophthalmitis and particularly to the spectrum of organisms involved.

PMID- 23960991
TI  - Non-viral microbial keratitis in children.
AB  - Microbial (non-viral) keratitis is a serious vision-threatening condition. The
      management of microbial keratitis in children is particularly complicated by the
      children's inability to cooperate during examinations and the lack of information
      prior to presentation. Predisposing factors vary according to geographical
      location and age. Corneal trauma is the leading cause for microbial keratitis in
      children, followed by systemic and ocular disease. Etiologic agents are most
      frequently Gram-positive and Gram-negative bacteria commonly found in contact
      lens-related microbial keratitis. Mycotic keratitis is a major risk factor in
      tropical weather conditions, particularly when associated with agricultural
      trauma. Early diagnosis, intensive drug treatment, and timely planned surgical
      intervention may effectively improve the outcome of pediatric microbial
      keratitis. 

PMID- 23960993
TI  - Histochemical analysis and immunohistochemical profile of mucoepidermoid
      carcinoma of the conjunctiva.
AB  - PURPOSE: To elucidate the distinct histochemical and immunohistochemical profile
      of mucoepidermoid carcinoma of the conjunctiva (MECC) and to determine which
      combination of stains is most useful in diagnosing MECC and differentiating it
      from squamous cell carcinoma of the conjunctiva (SCC) in cases where the clinical
      or cytological findings are not definitive. METHODS: Eight specimen of MECC from
      4 patients and 4 specimens of SCC from 4 patients were examined using a variety
      of special stains and immunohistochemical markers. The results were then analyzed
      for usefulness in diagnosing MECC. RESULTS: The most useful markers in diagnosing
      MECC and differentiating it from SCC are mucicarmine, colloidal iron, and alcian
      blue all with sensitivities of 88%, and a specificity of 100%; CEA with a
      sensitivity of 83% and a specificity of 75%; and, mucin-1 with a sensitivity of
      100% and a specificity of 25%, but which showed a distinct pattern of staining of
      MECC when compared to SCC. In our series, the sensitivity of the CK7+/CK20-
      combination for MECC was only 38%. CONCLUSIONS: The most useful stains in ruling
      out SCC in a suspected case of MECC were shown to be mucicarmine and the
      glycosaminoglycan (GAG) stains. However, in cases where mucicarmine and the GAG
      stains are negative or difficult to interpret and there is suspicion of a
      diagnosis of MECC, CEA and mucin-1 may be helpful for this diagnosis. The
      findings of CK7+/CK20- also may be of assistance, but are not as sensitive when
      compared to analogous salivary gland lesions, when differentiating MECC from SCC.

PMID- 23960992
TI  - Microsporidial keratitis: Literature review and report of 2 cases in a tertiary
      eye care center.
AB  - Microsporidia are getting more recognized as causative organism of ocular,
      gastrointestinal, renal, pulmonary, and sinus diseases, in both immunocompetent
      and immunosuppressed patients. Ocular microsporidiosis can be isolated or may
      present as part of systemic infection. Recent reports showed increasing number of
      cases of ocular microsporidiosis in immunocompetent individuals. The ocular type
      occurs mainly in two forms: keratoconjunctivitis form which is mostly seen in
      immunocompromised individuals and stromal keratitis form seen in immunocompetent
      individuals. The ocular cases which present with superficial keratitis in
      acquired immune deficiency syndrome (AIDS) patients differ from the cases seen in
      immunocompetent individuals which present mainly as deep stromal keratitis. We
      are presenting the only two documented cases of microsporidial keratitis
      diagnosed over 25 years of practice in our institution. The cases are diagnosed
      by identification of the Acid-fast organisms. Ultrastructure and additional
      information on species identification in one of the cases. Both cases are
      eventually managed by therapeutic PKP. Diagnosis and treatment modalities are
      discussed based on a comprehensive literature review. 

PMID- 23960994
TI  - Epidemiology of benign eyelid lesions in patients presenting to a teaching
      hospital.
AB  - PURPOSE: This study evaluates the relative frequency of benign eyelid lesions
      presented to a teaching hospital in Saudi population. PATIENTS AND METHODS:
      Charts of patients with benign eyelid lesions were retrospectively reviewed from
      January 2003 to December 2008. Clinical details included demographic data,
      symptoms and signs, surgical findings, primary diagnosis, and indication for
      biopsy were analyzed in a histopathologically confirmed benign eyelid lesions.
      Eyelid lesions were arranged according to their order of frequencies. RESULTS: A
      total of 222 biopsies were evaluated from 181 patients (male 39.2% and female
      60.8%). The age of the patient at the time of biopsy ranged from 2 to 87 years
      old. The most common benign eyelid lesion encountered in our practice was sweat
      gland hidrocystoma followed by chalazion, skin tag, epidermal cyst, nevus,
      seborrheic keratosis, xanthelasma, and molluscum contagiosum respectively.
      Histopathological studies confirmed the clinical diagnosis in 95.9% (213/222) of
      specimens and was different from the clinical diagnosis in 4.1% (9/222) of the
      lesions which included seborrheic keratosis (n = 3), pilomatrixoma,
      steatocystoma, hemangioendothelioma, juvenile xanthogranuloma, calcinosis cutis,
      and syringocystadenoma papilliferum. No malignant lesion was labeled as benign.
      CONCLUSION: Epidemiology of benign eyelid lesions in Saudi population is
      different from Far East or Western populations. Sweat gland hidrocystoma with
      classical clinical features and straightforward diagnosis is the most frequent
      lesion in our series which could be due to characteristic dry climate.

PMID- 23960996
TI  - Value of microbiology study in congenital nasolacrimal duct obstruction.
AB  - PURPOSE: Evaluation of the effect of different microorganisms on congenital
      nasolacrimal duct obstruction (CNLDO) tightness and whether probing or silastic
      intubation is likely to fail in a particular microorganism infection. METHODS:
      The culture and sensitivity results of lacrimal drainage system (LDS) discharge
      samples from patients with CNLDO were reviewed. Different microorganisms were
      correlated with the severity of nasolacrimal duct (NLD) obstruction observed
      during surgical intervention. The success rates of probing and silastic
      intubation as a primary procedure for each identifiable microorganism were
      documented. Statistical analysis was conducted to correlate the type of
      microorganism with the tightness of CNLDO and treatment failure. RESULTS: Out of
      181 specimens, 22 had no growth (12.1%). LDS with positive culture had 76.6%
      successful probing (n = 49) and 82.1% successful silastic intubation (n = 78).
      Gram-positive and Gram-negative species were almost equally detected. The most
      prevalent organisms were Streptococcus pneumoniae and Hemophilus influenzae
      (48.1% and 39.2%, respectively). Tight CNLDO was more prevalent in Serratia
      marcescens (n = 2; 100%) and Staphylococcus aureus (n = 4; 33.3%) infections with
      a 7.75 Odds ratio [95% confidence interval (CI), 1.67-34.63]. Staphylococcus
      aureus had 37.5% successful probing; however, success was achieved in all cases
      with silastic intubation. Serratia marcescens infections had 100% successful
      silastic intubation. CONCLUSION: Microbiology study can predict tight CNLDO and
      helps in choosing the most successful treatment option. CNLDO with Staphylococcus
      infection and Serratia marcescens were likely to have tight NLD obstruction and
      silastic intubation had better outcomes.

PMID- 23960995
TI  - Incidence and microbiological profile of mycotic keratitis in a tertiary care eye
      hospital: A retrospective analysis.
AB  - PURPOSE: To determine the incidence and microbiological profile of mycotic
      keratitis seen at a tertiary care eye hospital. MATERIALS AND METHODS: A
      retrospective review of microbiology records of patients presenting with
      suspected microbial keratitis seen between January 2006 and December 2009 was
      performed. Patients with positive fungal cultures were further analyzed for the
      type of fungus isolated and associated bacterial pathogens. RESULTS: Microbiology
      records of 2300 patients with suspected microbial keratitis were reviewed. A
      microbiological diagnosis of mycotic keratitis was established in 87 (3.8%)
      patients over a four year period based on positive fungal cultures. The yearly
      incidence of mycotic keratitis was 3.2% (2006), 4.9% (2007), 3.3% (2008) and 3.6%
      (2009). Filamentous fungi were isolated more often than yeasts. Aspergillus
      species followed by Fusarium species and Trichophyton species were the commonest
      filamentous fungi isolated while Candida albicans was the most frequently
      encountered yeast. Mixed infections due to fungal and bacterial pathogens were
      seen in 25/87 (28.7%) patients. CONCLUSION: Cumulative incidence of mycotic
      keratitis was 3.8% over a four year period. Aspergillus species and Candida
      albicans were the most frequent pathogenic organisms causing mycotic keratitis in
      this part of the world. Mixed infections were seen in 28.7% of the patients.
      Knowledge of the "local" etiology within a region may be valuable in the
      management of mycotic keratitis in instituting an empirical therapy, especially
      when facilities for microscopy, cultures and antifungal susceptibility are not
      readily available. The baseline information presented will also be helpful in the
      planning of a corneal ulcer management strategy and for future studies on mycotic
      keratitis.

PMID- 23960997
TI  - Familial bilateral combined hamartoma of retina and retinal pigment epithelium
      associated with neurofibromatosis 1.
AB  - We report a family of three siblings followed between 2005 and 2011 with
      bilateral combined hamartoma of the retina and retinal pigment epithelium, with
      the age of diagnosis ranging from 7 to 13 years. The main reason for consultation
      was reduction of vision and squint. The diagnosis was determined based on the
      clinical findings on fundus examination: increased pigmentation at the macula
      with slightly elevated, gray-white macular lesion, tortuosity of perimacular
      blood vessels and glial epiretinal membrane. The elder brother was found to have
      left posterior subcapsular cataract. He was also confirmed to have
      neurofibromatosis type 1, the youngest sister fit in the diagnostic criteria for
      neurofibromatosis type 1, while the middle sister was presumed to have
      neurofibromatosis type 1. Follow-up showed stability of the retinal lesion in the
      three cases, with the progression to develop right posterior subcapsular cataract
      in the elder sister. This report is aimed to demonstrate that the occurrence of
      bilateral combined hamartoma of the retina and retinal pigment epithelium could
      raise the possibility of associated neurofibromatosis. 

PMID- 23960998
TI  - Diffuse large B-cell lymphoma of the orbit: A tertiary eye care center experience
      in Saudi Arabia.
AB  - Primary Diffuse Large B-cell Lymphoma (DLBCL) represents the 2nd most common
      lymphoma occurring in the orbit, after Mucosal Associated Lymphoid Tissue (MALT)
      lymphoma. A total of 5 cases of ocular adnexal DLBCL were diagnosed over 25 years
      of experience at our tertiary eye care center. Two cases involved the lacrimal
      sac and one case involved the lacrimal gland. In this paper we are presenting the
      remaining 2 non-lacrimal cases of DLBCL. The first case is a 32 year old male who
      was referred with a slowly growing, painless mass involving the left medial
      canthal area as a case of dacryocystitis. The mass was found to be extending into
      the orbit inferiorly with upward displacement of the left globe. The second case
      is a 65 year-old lady who presented with unilateral proptosis as a result of a
      right orbital mass extending to the orbital apex. Histopathologic examination and
      immunohistochemical analysis of the incisional biopsy in both cases confirmed the
      diagnosis of Diffuse Large B-cell Lymphoma (DLBCL). 

PMID- 23960999
TI  - Unilateral eyelid swelling, proptosis and diplopia as initial manifestation of
      acute myeloid leukemia.
AB  - Myeloid sarcoma is a tumor of immature myeloid cells occurring in many
      extramedullary sites, orbit being one of them where the tumor may occur prior to
      or after the diagnosis of underlying disease. We report a case of a 17-year-old
      male who presented with upper eyelid swelling, proptosis and diplopia after
      presumed blunt trauma without any other clinical signs and symptoms. Initial
      imaging suggested possibility of subperiosteal hematoma. Magnetic resonance
      imaging studies demonstrated a solid tumor. Complete excision of the tumor and
      histopathologic diagnosis revealed evidence of acute myeloid leukemia (AML).
      There were no other sites indicating any tumoral process; however, bone marrow
      aspirate revealed an evidence of systemic disease. After chemotherapy and
      allogenic bone marrow transplant, the patient had complete remission of his
      disease. An episode of graft vs host reaction resulting in severe dry eyes along
      with skin eruptions was treated successfully by immunosuppression and topical
      lubrication without any visual or systemic sequela. This case emphasizes on the
      need for an aggressive work-up for any unusual orbital lesion in the absence of
      any explainable etiology. Further, AML may be suspected in the cases of orbital
      tumors even in the absence of systemic manifestations of leukemia at any age. 

PMID- 23961000
TI  - Healed corneal ulcer with keloid formation.
AB  - We are reporting a 34-year-old Arabic white female patient who presented with a
      white mass covering her left cornea following multiple ocular surgeries and
      healed corneal ulcer. The lesion obscured further view of the iris, pupil and
      lens. The patient underwent penetrating keratoplasty and the histopathologic
      study of the left corneal button showed epithelial hyperplasia, absent Bowman's
      layer and subepithelial fibrovascular proliferation. The histopathologic
      appearance was suggestive of a corneal keloid which was supported by further
      ultrastructural study. The corneal graft remained clear 6 months after surgery
      and the patient was satisfied with the visual outcome. Penetrating keratoplasty
      may be an effective surgical option for corneal keloids in young adult patients. 

PMID- 23961001
TI  - Choroidal metastasis as the presenting feature in a case of testicular
      choriocarcinoma.
AB  - A twenty-six year old male with decreased vision in right eye was diagnosed with
      non-rhegmatogenous retinal detachment. Further evaluation revealed a yet
      undiagnosed left testicular mass found to be choriocarcinoma on histopathology.
      Chemotherapy resulted in complete remission; however, there was no improvement in
      vision. There is a substantial risk of visual loss in the presence of ocular
      metastatic lesions. Early detection and treatment is highly effective in terms of
      tumor control and a more favorable survival and visual outcome. The onus of the
      ocular diagnosis lies on the ophthalmologist. The presence of a testicular origin
      tumor must be considered in a young male with intraocular metastasis. 

PMID- 23961002
TI  - Pediatric Ophthalmology: Changing with the times.

PMID- 23961003
TI  - Evaluation and management of pediatric rhegmatogenous retinal detachment.
AB  - Pediatric rhegmatogenous retinal detachments are rare, accounting for less than
      ten percent of all rhegmatogenous retinal detachments. While most retinal
      detachments in the adult population are related to posterior vitreous detachment,
      pediatric retinal detachment are often related to trauma or an underlying
      congenital abnormalities or genetic syndrome. The anatomy of pediatric eyes, the
      often late presentation of the disease, and the high incidence of bilateral
      pathology in children all pose significant challenges in the management of these
      patients. We discuss the epidemiology of pediatric rhegmatogenous retinal
      detachment, review the genetic syndromes associated with a high incidence of
      retinal detachment, and examine other common causes of retinal detachment in this
      age group. We then outline an approach to evaluation and management and describe
      the expected outcomes of repair of retinal detachment in the pediatric
      population. 

PMID- 23961004
TI  - Comitant strabismus: Perspectives, present and future.
AB  - Comitant strabismus is a common condition affecting infants, children and adults.
      Its impact on the affected patient may be severe resulting in visual loss, lack
      of binocularity, diplopia, social stigma and multiple corrective surgeries within
      the affected individual's lifespan. It is therefore important that this prevalent
      disorder should be better understood. We review the current understanding of the
      demographics and what is known of the etiology, risk factors and genetics of
      strabismus. We stress the importance of careful clinical assessment in
      classifying strabismus, and the common pitfalls in the measurement and pre
      operative sensory work-up of the strabismic patient. The fact strabismus is
      comitant does not indicate it is benign: acute onset of comitant esotropia may be
      a presenting sign of pontine or cerebellar tumor. Lastly, we review the impact of
      genetics on our understanding of strabismus. While the causes of many types of
      congenital incomitant strabismus have been elucidated through careful observation
      and genetic screening, the genetics of comitant strabismus are more complex and
      multifactorial. Only through careful study and recruitment of large groups of
      affected individuals and families can we start to answer the question: why is
      this group of patients pre-disposed to develop strabismus. Doing so will help
      identify patients at risk, to spare them from the significant morbidity
      associated with this common disorder. 

PMID- 23961005
TI  - Update of intraocular lens implantation in children.
AB  - Cataract is a common problem that affects the vision in children and a major
      cause of amblyopia in children. However, the management of childhood cataract is
      tenuous and requires special considerations especially with regard to intraocular
      lens (IOL) implantation. Age at which an IOL can be implanted is a controversial
      issue. Implanting an IOL in very young children carries the risk of severe
      postoperative inflammation and posterior capsule opacification that may need
      other surgeries and may affect the vision permanently. Accuracy of the calculated
      IOL power is affected by the short eyes and the steep keratometric values at this
      age. Furthermore, choosing an appropriate IOL power is not a straight forward
      decision as future growth of the eye affects the axial length and keratometry
      readings which may result in an unexpected refractive error as children age. The
      aim of this review is to cover these issues regarding IOL implantation in
      children; indications, timing of implantation, types of IOLs, site of
      implantation and the power calculations. 

PMID- 23961006
TI  - Orbital trapdoor fractures.
AB  - Orbital trapdoor fractures are commonly encountered in children. Awareness of
      trapdoor fractures is of particular importance. This is because early recognition
      and treatment are necessary to prevent permanent motility abnormities. In this
      article, we will provide a brief overview of orbital fractures. The clinical and
      radiographic features of trapdoor fractures will then be reviewed, followed by a
      discussion on their proper management. 

PMID- 23961007
TI  - Infantile hemangiomas: A review.
AB  - Infantile hemangiomas (IH) are the most common eyelid and orbital tumors of
      childhood. Although they are considered benign lesions that have a generally self
      limited course, in the periocular region, they have the potential to cause
      amblyopia, strabismus, and severe disfigurement. The decision for treatment can
      be a source of anxiety for patients, parents, and physicians alike. There are
      numerous treatment modalities, including emerging therapies that may make
      treatment safer and more effective than ever before. This review discusses our
      current understanding of this disease, its management, and future therapies. 

PMID- 23961008
TI  - Juvenile myopia progression, risk factors and interventions.
AB  - The development and progression of early onset myopia is actively being
      investigated. While myopia is often considered a benign condition it should be
      considered a public health problem for its visual, quality of life, and economic
      consequences. Nearly half of the visually impaired population in the world has
      uncorrected refractive errors, with myopia a high percent of that group.
      Uncorrected visual acuity should be screened for and treated in order to improve
      academic performance, career opportunities and socio-economic status. Genetic and
      environmental factors contribute to the onset and progression of myopia. Twin
      studies have supported genetic factors and research continues to identify myopia
      genetic loci. While multiple myopia genetic loci have been identified
      establishing myopia as a common complex disorder, there is not yet a genetic
      model explaining myopia progression in populations. Environmental factors include
      near work, education levels, urban compared to rural location, and time spent
      outdoors. In this field of study where there continues to be etiology
      controversies, there is recent agreement that children who spend more time
      outdoors are less likely to become myopic. Worldwide population studies, some
      completed and some in progress, with a common protocol are gathering both genetic
      and environmental cohort data of great value. There have been rapid population
      changes in prevalence rates supporting an environmental influence. Interventions
      to prevent juvenile myopia progression include pharmacologic agents, glasses and
      contact lenses. Pharmacological interventions over 1-2 year trials have shown
      benefits. Peripheral vision defocus has been found to affect the emmetropization
      process and may be affected by wearing glasses or contacts. Accommodation
      accuracy also has been implicated in myopia progression. Further research will
      aim to assess both the role and interaction of environmental influences and
      genetic factors. 

PMID- 23961009
TI  - Long term visual outcomes in laser treated threshold retinopathy of prematurity
      in Central Saudi Arabia.
AB  - PURPOSE: To assess the long term visual outcomes and refractive status of
      patients who underwent diode laser for threshold retinopathy of prematurity (ROP)
      and to investigate the risk factors leading to poor visual outcomes. METHODS:
      Fifty-seven patients (114 eyes) with threshold ROP who underwent laser therapy
      were contacted for reassessment. A chart review was performed for all patients to
      collect data on visual acuity, retinal status and strabismus. A favorable visual
      outcome was defined as ?20/160 (Snellen acuity) for young adults (cooperative
      patients), and ?CSM for children (uncooperative patients) while unfavorable
      visual outcome was defined as <20/160 or <CSM. Vision in uncooperative children
      was graded as central, steady, maintain. Descriptive and inferential analyses
      were conducted. Chi(2) and odds ratios were calculated whenever appropriate. A P
      value <0.05 was considered as statistically significant. RESULTS: The mean age at
      reassessment was 5.2 +/- 2.5 years (range, 1-10 years) where 36 (63.2%) patients
      were males and 21 (36.8%) were females. Out Of the 114 laser treated eyes, 73
      (64%) were myopic, with mean spherical equivalent (SE) of -6.69 (5.9), range (
      0.25 to -21) diaopters, 8 (7%) were emmetrope, while other 33 (29%) were
      hyperopic with mean SE of +2.43 (3.04), range (+0.25 to +17) diaopters.
      Strabismus was present in 31 patients (54.4%) of whom 81% (25/31) were esotropic.
      Retina was found to be normal in 77.1% of the examined eyes, while the remaining
      eyes had either macular dragging or retinal detachment. Almost 70% of the eyes
      with a normal retinal examination had favorable visual outcome. Thirteen (11.4%)
      eyes had zone 1 retinopathy, 83 (72.8%) eyes had zone 2 retinopathy and 2 (1.8%)
      eyes had zone 3 retinopathy. Vitreous hemorrhage was present in 7 (6.1%) eyes
      prior to laser treatment. The relationship between final retinal status and
      visual outcome was statistically significant (P < 0.0001). There was no
      statistically significant correlation between visual outcome and the zone of the
      retinopathy (P = 0.448). CONCLUSION: The majority of patients who underwent diode
      laser therapy for threshold ROP had favorable anatomical and visual outcomes.
      However, high refractive error and strabismus may be clinically the pertinent
      causes of visual impairment.

PMID- 23961010
TI  - Compliance to patching in the treatment of amblyopia.
AB  - PURPOSE: To evaluate compliance of amblyopic patients to patching, and to
      identify reasons of poor compliance and suggest methods to overcome the problem.
      METHODS: We conducted a cross-sectional, retrospective study that included 37
      families with a child diagnosed with unilateral amblyopia (age range 3-16 years)
      and attending the Pediatrics Ophthalmology clinic at the King Abdulaziz
      University Hospital (a tertiary eye hospital). Data were collected through
      interviews and from hospital charts. In the interviews we asked questions that
      sought information with regard to four aspects (domains); knowledge, attitude,
      insight and community's effect. A score representing each domain was given to
      every family then we correlated these scores with family's compliance percentage.
      RESULTS: When correlated with compliance, the insight and attitude domains showed
      a statistically significant correlation; p-value 0.002 and 0.004, respectively.
      However, the knowledge and community's effect domains were not; p-value 0.084 and
      0.114, respectively. Other qualitative factors affecting compliance were
      identified with open questions. Quotes from families of what they think can
      improve compliance are shown. CONCLUSION: To improve compliance, merely educating
      patients is not sufficient and more efforts should be undertaken toward ensuring
      true sense of the problem and its impact. Factors affecting compliance due to the
      physical properties in the patch itself should be addressed too (heat,
      irritation, poor adhesive material and design).

PMID- 23961011
TI  - Descemet stripping automated endothelial keratoplasty in pediatric age group.
AB  - PURPOSE: To report the outcomes of DSAEK surgery performed in pediatric patients.
      DESIGN: Noncomparative interventional case series. SUBJECTS AND METHODS: All
      pediatric patients (age up to 16 years) undergoing Descemet automated stripping
      endothelial keratoplasty (DSAEK) at our Institution since January 2008 have been
      enrolled in a prospective study. A standard DSAEK, involving delivery of an 8.5
      9.5 mm graft by Busin glide, was performed under general anesthesia in 19 eyes of
      11 pediatric patients (congenital hereditary endothelial dystrophy n = 13;
      congenital glaucoma n = 2; posterior polymorphous dystrophy n = 2, and failed
      penetrating keratoplasty n = 2). Slit-lamp examination, refraction and visual
      acuity as well as endothelial cell density were evaluated preoperatively as well
      as 1, 3, 6, 12, and 18 months postoperatively. RESULTS: All surgical procedures
      were uneventful. Graft detachment occurred in 4 cases and was managed
      successfully with repeat air injection. All corneas cleared within a week from
      surgery. Follow-up was 3-18 months. At last follow-up examination, best-corrected
      visual acuity (BCVA) was better than 20/40 in 8 of the 13 cases of patients old
      enough to assess vision. A graft rejection episode was seen in 1 case within 3
      months from surgery but was reverted with steroidal treatment. No graft failures
      were observed. CONCLUSIONS: DSAEK is an appropriate surgical intervention for
      children with corneal endothelial failure. In contrast to penetrating
      keratoplasty (PK), DSAEK is performed under "closed system" conditions, thus
      minimizing intraoperative risks. Finally, healing is much faster than with PK and
      all sutures can be removed within 2-4 weeks from surgery, thus allowing fast
      visual recovery and prompt starting of amblyopia treatment.

PMID- 23961012
TI  - Surgical management of non-traumatic pediatric ectopia lentis: A case series and
      review of the literature.
AB  - PURPOSE: To report a small series of pediatric patients with ectopia lentis that
      underwent limbal-approach lensectomy and vitrectomy and scleral-fixated
      intraocular lens implantation and to review the literature on the topic of
      surgical management of ectopia lentis. METHOD: A retrospective review of 13 eyes
      of seven patients that underwent lensectomy, vitrectomy, and scleral-fixated
      intraocular lens implantation and a review of the ophthalmic literature. RESULTS:
      In our series, the average age at surgery was 70.3 +/- 13.8 months and the
      average length of follow-up was 23.8 +/- 5.9 months. The mean pre-operative
      visual acuity was 0.86 +/- 0.17 which improved to 0.23 +/- 0.09 post-operatively
      (p < 0.001). No complications were encountered in our series. A review of the
      literature found that amblyopia was the biggest vision-limiting factor. In
      general, the literature suggested that a higher percentage of eyes that were left
      aphakic achieved better vision than those implanted with a scleral-fixated
      intraocular lens. However, there may be selection bias in that more eyes
      receiving an intraocular lens may have pre-existing amblyopia. The complication
      rates for lensectomy or scleral-fixated intraocular lens implantation were low in
      the literature. In the latter group, suture breakage and resultant intraocular
      lens dislocation is a worrisome late complication. CONCLUSION: Surgical
      intervention for ectopia lentis via vitrectomy techniques yields good result. In
      cases of unilateral aphakia or in settings where compliance with aphakic
      refractive correction is questionable and amblyopia is a constant threat, scleral
      fixated intraocular lens implantation is highly encouraged. However, long-term
      follow-up is required due to the risk of suture breakage and resultant
      intraocular lens dislocation over time.

PMID- 23961013
TI  - Long term comparison between single stage Baerveldt and Ahmed glaucoma implants
      in pediatric glaucoma.
AB  - PURPOSE: To compare the long term intraocular pressure control in pediatric
      glaucoma patients who underwent single stage Baerveldt glaucoma valve and Ahmed
      glaucoma valve S2 implantation. STUDY DESIGN: A retrospective study was conducted
      to analyze the data of patients with single stage Baerveldt glaucoma valve and
      Ahmed valve implantation at Children Hospital Los Angeles. METHODS: Medical
      records of patients were reviewed retrospectively and divided into two groups.
      All cases received single stage valve implantation in which the tube was inserted
      primarily into the anterior chamber. In cases with Baerveldt implants, the
      silicone tube was ligated near its plate location with a single absorbable
      suture. Group 1 included patients with Baerveldt glaucoma implant model BG 101
      350, while group 2 included patients with Ahmed valve implant model S-2.
      Patients' data collected ranged over the period from 2001 to 2008. The minimum
      follow up period was 6 month; maximum follow up period was 8 years. All patients
      were below 18 years of age. Success was considered if last postoperative IOP was
      between 8 and 24 mm Hg (with or without medications), no additional glaucoma
      surgery after valve implantation, and absence of visually significant
      complications. RESULTS: Group 1 included 20 cases and group 2 included 11 cases.
      Long term success rate based on criterion defined was 80% for group 1 (Baerveldt)
      with average IOP postoperatively on last follow-up of 19.6 mm Hg. In group 2
      (Ahmed), average postoperative pressure was 24 mm Hg with 6 out of 11 considered
      successful based on criterion giving 54.5% success rate. CONCLUSION: In the long
      term, single stage Baerveldt implantation appears to control pressure well in
      pediatric glaucoma.

PMID- 23961015
TI  - A case of bilateral uveitis and optic disc swelling with Chiari I malformation.
AB  - We report a case of bilateral uveitis and optic disc swelling with Chiari I
      malformation. A 16-year-old girl was admitted to our clinic due to conjunctival
      hyperaemia and blurred vision in her right eye. Ophthalmologic and systemic
      examinations were performed. Visual acuity was 0.7 (OD) and 1.0 (OS). Bilateral
      optic disc swelling was observed. Fluorescein angiography demonstrated bilateral
      retinal vasculitis as well as optic disc hyperflourescence due to leakage.
      Laboratory examinations were within normal limits. Cranial magnetic resonance
      venography imaging revealed neither cranial mass nor cerebral venous thrombosis
      but a Chiari I malformation. The patient was started oral cetazolamid, topical
      and oral corticosteroids. After six months follow-up, bilateral optic disc
      swelling was resolved completely and visual acuity was 1.0 in both eyes. Optic
      disc swelling may be associated with intraocular inflammation; however, patients
      with bilateral optic disc swelling should be suspected of having an accompanying
      intracranial pathology. 

PMID- 23961014
TI  - Pattern of ocular injuries in stone pelters in Kashmir valley.
AB  - PURPOSE: To describe the pattern and types of ocular injuries in stone pelters in
      Kashmir valley during recent turmoil. DESIGN: Cross sectional study. METHODS:
      Sixty patients with different types of eye injuries were assessed between June
      September 2010 and initial visual acuity was recorded. The injuries were
      classified according to Systems for Classifying Ocular Injuries (OTCS) and Ocular
      Trauma Score (OTS) was calculated in order to estimate the probability of follow
      up visual acuity range. RESULTS: Most of the victims (75%) were young boys
      between 16-26 years with a mean age of 20.95, 95% of cases were males. The main
      cause of injury was stones (48.3%) and pellets (30%) besides rubber bullets,
      sling shots and tear gas shells. Most of the open-globe injuries due to stones
      were of Type B and A, Grade E, Zone II and III with Afferent Pupillary Defect
      (APD) in 30% of the cases. Closed-globe injuries were mostly of Type A, Grade C
      and D and Zone II and III. Most of the open-globe injuries due to pellets were of
      Type D, Grade D, Zone II and APD in 33.3%. Pellets Intra Ocular Foreign Body
      (IOFB) was in 41.6%. Most of the closed-globe injuries were of Type A, Grade D
      and E and of Zone III. Overall OTS of 1 was calculated in 16.6% and 3 in 53.3% of
      the cases. CONCLUSION: In stone pelting demonstrations eye injuries can result in
      visually significant trauma. Injuries due to pellets are mostly perforating and
      pellet IOFB, and both tend to have a very poor prognosis. OTS can be used to
      estimate visual prognosis.

PMID- 23961016
TI  - Asthenopia as the presenting symptom in advance allergic fungal sinusitis.
AB  - A 14-year-old male presented to the ophthalmology clinic with a history of
      asthenopia. Laboratory, radiological and histopathological studies confirmed the
      diagnosis of allergic fungal sinusitis resulting in lateral displacement of the
      medial rectus muscles. Symptoms improved and near point of convergence recovered
      after surgical endoscopic decompression of the ethmoidal and maxillary sinuses. 

PMID- 23961017
TI  - Spontaneous closure of traumatic macular hole.
AB  - Macular hole formation is a well-known complication following ocular trauma. Less
      commonly recognised is the spontaneous closure of such holes. A 27-year-old man
      presented with a history of blunt trauma to his left eye. Eye evaluation showed
      conjunctival laceration, diffuse retinal oedema and multiple retinal haemorrhages
      in that eye. A month later, he developed a full thickness macular hole. Two
      months later, there was spontaneous complete closure of the full-thickness
      macular hole in the left eye as confirmed on optical coherence tomography.
      Spontaneous closure of hole is not uncommon. Observation for a period of up to 12
      months is a reasonable management option. Macular hole surgery for traumatic
      macular holes may be delayed in such cases. 

PMID- 23961018
TI  - Update in oculoplastic imaging.

PMID- 23961020
TI  - Update on imaging techniques in oculoplastics.
AB  - Imaging is a beneficial aid to the oculoplastic surgeon especially in orbital and
      lacrimal disorders when the pathology is not visible from outside. It is a
      powerful tool that may be benefited in not only diagnosis but also management and
      follow-up. The most common imaging modalities required are CT and MRI, with CT
      being more frequently ordered by oculoplastic surgeons. Improvements in
      technology enabled the acquisition times to shorten incredibly. Radiologists can
      now obtain images with superb resolution, and isolate the site and tissue of
      interest from other structures with special techniques. Better contrast agents
      and 3D imaging capabilities make complicated cases easier to identify. Color
      Doppler imaging is becoming more popular both for research and clinical purposes.
      Magnetic resonance angiography (MRA) added so much to the vascular system imaging
      recently. Although angiography is still the gold standard, new software and
      techniques rendered MRA as valuable as angiography in most circumstances.
      Stereotactic navigation, although in use for a long time, recently became the
      focus of interest for the oculoplastic surgeon especially in orbital
      decompressions. Improvements in radiology and nuclear medicine techniques of
      lacrimal drainage system imaging provided more detailed analysis of the system. 

PMID- 23961019
TI  - Meibography: A review of techniques and technologies.
AB  - Meibomian glands play a significant role in tear production by contributing
      lipids to the superficial tear film.(1) Dysfunction of the meibomian glands
      destabilizes tears resulting in evaporative dry eye.(2,3) Historically, the
      meibomian glands were assessed in an ex vivo fashion through histologic studies.
      However, innovations in ocular imaging have advanced significantly in recent
      decades to include meibography. Meibography is an imaging study developed 35
      years ago exclusively for the purpose of observing the morphology of meibomian
      glands in vivo.(4,5) In this review of meibography, we briefly describe the
      etiology of meibomian gland dysfunction and then discuss various meibography
      techniques, technologies, and methods of image analysis. We close with a review
      of the literature, crediting various studies for the significant contributions
      made toward our current understanding of the meibomian glands. 

PMID- 23961021
TI  - Value of positron emission tomography/computed tomography in diagnosis and
      staging of primary ocular and orbital tumors.
AB  - Accurate and reliable staging methods are crucial for optimal care of patients
      with ocular and orbital malignancies. Positron emission tomography/computed
      tomography (PET/CT) has recently emerged as a staging tool in the field of
      ophthalmic oncology. For detecting primary ocular or orbital lesions, PET/CT does
      not seem to provide an advantage over clinical ophthalmologic examination or
      conventional imaging studies such as CT or magnetic resonance imaging of the
      orbit. However, PET/CT may detect distant metastatic lesions that conventional
      imaging studies miss. For orbital and ocular adnexal lymphoma, use of PET/CT has
      been proven to be feasible and is now accepted both as a standard part of the
      initial staging work-up and for the assessment of response to therapy. For other
      ophthalmic tumors, PET/CT seems most appropriate for advanced metastatic tumors
      of the orbit, eyelid, and eye, for which the detection of distant metastasis with
      1 comprehensive study may be preferable to performing multiple CT scans with
      contrast. 

PMID- 23961022
TI  - Orbital masses: CT and MRI of common vascular lesions, benign tumors, and
      malignancies.
AB  - A wide variety of space occupying lesions may be encountered in the orbit. CT and
      MR imaging frequently help confirm the presence of a mass and define its extent.
      Characteristic imaging features may help distinguish among lesions that have
      overlapping clinical presentations. This review focuses on some of the common
      orbital masses. Common vascular lesions that are reviewed include: capillary
      (infantile) hemangioma, cavernous hemangioma (solitary encapsulated venous
      lymphatic malformation), and lymphangioma (venous-lymphatic malformation). Benign
      tumors that are reviewed include: optic nerve sheath meningioma, schwannoma, and
      neurofibroma. Malignancies that are reviewed include: lymphoma, metastasis,
      rhabdomyosarcoma, and optic glioma. Key imaging features that guide radiological
      diagnosis are discussed and illustrated. 

PMID- 23961024
TI  - Recent advances in MRI technology: Implications for image quality and patient
      safety.
AB  - Recent advances in MRI technology are presented, with emphasis on how this new
      technology impacts clinical operations (better image quality, faster exam times,
      and improved throughput). In addition, implications for patient safety are
      discussed with emphasis on the risk of patient injury due to either high local
      specific absorption rate (SAR) or large cumulative energy doses delivered during
      long exam times. Patient comfort issues are examined as well. 

PMID- 23961023
TI  - Update on advanced imaging options for thyroid-associated orbitopathy.
AB  - Thyroid-associated orbitopathy (TAO) is a diverse spectrum of signs and symptoms
      that appears to have immunologic and pathologic causative factors as diverse as
      its clinical presentations. Lymphocytes, hormones, and cytokines affect orbital
      fibroblasts and other similar cells, which exert their effects on orbital
      tissues, including the extraocular muscles, orbital fat, and optic nerve. This
      complicated inflammatory cascade and the myriad of clinical findings that result
      contributes to the active phase of TAO. The distinction between the active and
      inactive phases of TAO is an important one, as the proper treatment will depend
      on the disease phase and degree thereof. Several clinical grading scales and
      scores have been established to help qualify and quantify the disease severity.
      Aiding clinical exam and acumen, proper and reproducible imaging of the orbit and
      ocular adnexa is incredibly important to the management of TAO. Orbital
      ultrasound, computed tomography, magnetic resonance imaging, and scintigraphy
      each have unique abilities, including quantifying orbital changes, assessing
      disease activity, correlating orbital findings with clinical changes, guiding
      appropriate treatment, and monitoring therapeutic responses. Further, study ease,
      accessibility, cost, sensitivity, specificity, reproducibility, and risks are all
      important considerations in picking the right test with which to diagnose and
      follow TAO. This analysis will provide a review of orbital imaging for TAO,
      including the mechanism of each imaging technique as well as their rationales,
      advantages, disadvantages, and utilities. 

PMID- 23961025
TI  - Neuroimaging in ophthalmology.
AB  - In the past three decades, there have been countless advances in imaging
      modalities that have revolutionized evaluation, management, and treatment of
      neuro-ophthalmic disorders. Non-invasive approaches for early detection and
      monitoring of treatments have decreased morbidity and mortality. Understanding of
      basic methods of imaging techniques and choice of imaging modalities in cases
      encountered in neuro-ophthalmology clinic is critical for proper evaluation of
      patients. Two main imaging modalities that are often used are computed tomography
      (CT) and magnetic resonance imaging (MRI). However, variations of these
      modalities and appropriate location of imaging must be considered in each
      clinical scenario. In this article, we review and summarize the best neuroimaging
      studies for specific neuro-ophthalmic indications and the diagnostic radiographic
      findings for important clinical entities. 

PMID- 23961026
TI  - Computed tomography of the orbit - A review and an update.
AB  - Computed tomography (CT) and magnetic resonance imaging (MRI) of the orbit have
      been competing for the hearts and minds of health care providers for well over 2
      decades. While several drawbacks pertaining to CT have been outlined since the
      introduction of MRI, CT remains the standard diagnostic test for evaluating cross
      sectional, 2 or 3-dimensional images of the body. 

PMID- 23961027
TI  - Fungal rhinosinusitis and imaging modalities.
AB  - This report provides an overview of fungal rhinosinusitis with a particular focus
      on acute fulminant invasive fungal sinusitis (AFIFS). Imaging modalities and
      findings that aid in diagnosis and surgical planning are reviewed with a
      pathophysiologic focus. In addition, the differential diagnosis based on imaging
      suggestive of AFIFS is considered. 

PMID- 23961029
TI  - Glaucoma masqueraders: Diagnosis by spectral domain optical coherence tomography.
AB  - BACKGROUND: Advances in optic nerve and retinal imaging have dramatically changed
      the care of glaucoma patients, complementing the importance of the clinical exam
      of the optic nerve and automated perimetry in making the diagnosis of glaucoma.
      Computerized imaging, however, does not replace the clinical exam, as there can
      be overlap in the appearance of non-glaucomatous optic neuropathies with
      glaucoma. METHODS: The spectral domain optic coherence tomography (SD-OCT) images
      of five patients with non-glaucomatous optic nerve pathology are presented.
      CASES: The first patient had bilateral temporal thinning on OCT imaging and
      subsequent positive syphilis testing. The second patient had a glaucomatous
      appearing inferior arcuate scotoma and associated superior thinning on OCT; these
      findings were due to buried optic nerve head drusen, clearly appreciated on OCT
      of the optic nerve head. Bilateral diffuse macular thinning, with preservation of
      the superior and inferior fiber bundles, was seen in the third patient, who had
      multiple sclerosis, with no clinical history of optic neuritis. Dense and marked
      thinning of a macular half, respecting the horizontal meridian, is seen in two
      patients, one patient with non-arteritic anterior ischemic optic neuropathy and
      lastly, in a patient with hemi-retinal vein occlusion. CONCLUSION: SD-OCT of the
      optic nerve and retina complements the essential clinical examination of patients
      with glaucomatous and non-glaucomatous optic neuropathies.

PMID- 23961028
TI  - Imaging in orbital trauma.
AB  - Orbital trauma is one of the most common reasons for ophthalmology specialty
      consultation in the emergency department setting. We survey the literature from
      1990 to present to describe the role of computed tomography (CT), magnetic
      resonance imaging (MRI) and their associated angiography in some of the most
      commonly encountered orbital trauma conditions. CT orbit can often detect certain
      types of foreign bodies, lens dislocation, ruptured globe, choroidal or retinal
      detachments, or cavernous sinus thrombosis and thus complement a bedside
      ophthalmic exam that can sometimes be limited in the setting of trauma. CT
      remains the workhorse for acute orbital trauma owing to its rapidity and ability
      to delineate bony abnormalities; however MRI remains an important modality in
      special circumstances such as soft tissue assessment or with organic foreign
      bodies. 

PMID- 23961030
TI  - Imaging of eyelid lymphatic drainage.
AB  - PURPOSE: Traditional descriptions of lymphatic drainage show eyelids emptying
      into the submandibular or preauricular basin. However recent studies based on in
      vivo lymphatic imaging show a possible predilection for the preauricular basin.
      We describe lymphoscintigraphy and report findings in patients with eyelid
      malignancies undergoing sentinel lymph node biopsy (SLNB). METHODS: Retrospective
      chart review of 15 consecutive patients at a single institution with eyelid
      carcinoma undergoing SLNB. The primary outcome measure was primary facial
      lymphatic drainage site from the eyelid as determined by lymphoscintigraphy.
      RESULTS: The preauricular basin was the site of focal radioactive uptake in all
      15 patients. The location of the primary tumor was as follows: medial upper
      eyelid (1), medial canthus (3), medial lower eyelid (3), lateral upper eyelid
      (3), and lateral lower eyelid (5). The types of tumor were: invasive squamous
      cell carcinoma (7), malignant melanoma (3), and sebaceous cell carcinoma (2),
      Merkel cell carcinoma (2), and conjunctival spindle cell carcinoma (1).
      CONCLUSIONS: Lymphoscintigraphy is increasingly used in the context of SLNB for
      periocular malignancy. The recent literature suggests that the preauricular lymph
      node basin may be the primary site of eyelid lymphatic drainage and this is
      corroborated by our series. Further data will elucidate the biology of eyelid
      lymphatic channels in humans but the preauricular basin may be the prime
      lymphatic metastastic site in eyelid malignancies.

PMID- 23961031
TI  - Papilledema and optic disc pit: The association of two pathologies in one
      patient.
AB  - Histologically, optic disc pit (ODP) is described as a small congenital defect in
      the cribriform plate where a herniation of the dysplastic retina extends to the
      subarachnoid space in the optic nerve, which is surrounded by a layer of collagen
      rich tissue. Approximately 25-75% of cases are complicated by optic disc pit
      maculopathy (ODPM). The pathogenesis of maculopathies associated with ODP has not
      been fully elucidated. We present an unusual case of a patient with a history of
      papilledema secondary to a fronto-temporal meningioma. The patient underwent a
      successful surgical intervention with resolution of the papilledema 15 years
      before the detection of an ODP that was associated with retinal detachment in the
      macular region. Several studies have reported on the importance of intracranial
      pressure in the development of maculopathies associated with ODP. During the
      period of intracranial hypertension and papilledema in our patient, the hernia
      sac that was associated with ODP may have been small, which would have decreased
      the chances of developing a maculopathy that was associated with OPD. 

PMID- 23961032
TI  - Unilateral optic neuritis, scleritis and exudative retinal detachment due to
      recurrent orbital pseudotumor.
AB  - Idiopathic orbital inflammation, also known as orbital pseudotumor, describes a
      spectrum of idiopathic, non-neoplastic, non-infectious, space-occupying orbital
      lesions without identifiable local or systemic cause. The condition occurs mainly
      in young adults who may present with acute pain, proptosis, chemosis and
      limitations of extraocular movements. Decreased vision due to optic nerve
      infiltration and macular edema as a result of scleritis is less common sequel of
      orbital pseudotumor. Herein, we present a case of unilateral orbital pseudotumor
      in a young male who presented with chief complaints of painful decreased vision
      which was attributed to optic neuritis and macular edema as a result of
      scleritis. Imaging studies were helpful in the establishment of the correct
      diagnosis and patient's complaints improved with administration of systemic
      corticosteroids. 

PMID- 23961033
TI  - Slow-growing large pleomorphic adenoma of ectopic lacrimal gland tissue in the
      upper eyelid.
AB  - A few cases of pleomorphic adenoma of an ectopic lacrimal gland involving the
      deep orbit and lateral canthus have been previously reported. A 75-year-old
      female with a slow-growing, large pleomorphic adenoma arising from ectopic
      lacrimal gland tissue in the left upper eyelid is described in the present case
      report. 

PMID- 23961034
TI  - Orbital cysticercosis: A case report.
AB  - A 22 years old male presented to us with a history of lid swelling and chemosis
      of conjunctiva since 2 days. The patient had a history of convulsions 4 days back
      and 2 months back. The patient had undergone a CT scan which showed granulomas in
      temporal and parietal lobes. The patient was started on Anti tuberculosis
      treatment by the Physician. The Patient underwent USG B scan which revealed
      cysticercosis cyst in the anterior orbit inferiorly .The patient was treated with
      albendazole and wysolone for a month. The patient was reviewed after 1 month .The
      lesion resolved with the treatment both clinically and on USG. 

PMID- 23961035
TI  - Sphenoidal mucocele presenting as acute cranial nerve palsies.
AB  - Sphenoidal sinus mucoceles are indolent lesions that, when sufficiently large,
      can compress on the optic canal or superior orbital fissure, rapidly causing loss
      of vision, optic neuropathy, ptosis, pain, ophthalmoplegia, and diplopia. We
      herein report a 72-year-old gentleman who presented acutely with Cranial Nerve
      II, III, and IV palsies secondary to a sphenoidal sinus mucocele that was
      confirmed on magnetic resonance imaging and successfully treated with endoscopic
      drainage. This cause of orbital apex syndrome is important for clinicians to know
      as early diagnosis and treatment is critical in recovering visual potential. 

PMID- 23961036
TI  - Biological effects of some natural and chemical compounds on the potato tuber
      moth, Phthorimaea operculella Zell. (Lepidoptera:Gelechiidae).
AB  - The olfactory reaction of larvae and moths was investigated towards 18 oils (6
      natural oils and 12 commercial chemical oils). Some of these oils such as
      peppermint and camphor (natural oils) and eugenol and camphene (commercial oils)
      were repellent to both larvae and moths. Other oils such as strawberry and d
      limonene were attractive to both larvae and moths. Some of the repellent oils
      were, therefore, tested for their effect on certain biological aspects of the
      insects. Eugenol and peppermint oils, each at the 0.01% conc., caused a
      significant depression in the fecundity of moth and decreased the percentage of
      egg hatchability. Eugenol oil was much more effective than peppermint oil at 1%.
      Dried (leaves, fruits or seeds) powder of 14 different plants species were tested
      in different concentrations with talcum powder (carrier material) against egg
      deposition. The results indicated that dried powders of Allium cepa, Curcuma
      longa, Colocasia antiqurum, Ocimum basilicum. Dodonaea viscose and Thuja
      orientalis played a highly significant role in reducing egg deposition. The most
      impressive effect was displayed by powders of D. viscose and A. cepa, which
      caused the highest depression in egg deposition as well as in the emerging
      offsprings. Ethanolic extracts of 11 plants indicated that extracts of
      Pithuranthos tortosus and Iphiona scabra caused the maximum inhibition of egg
      hatchability, followed by C. longa, Citrullus colocynthia and T. orientalis.
      Ethanolic extracts of Schinus terebenthiflius (leaves) and I. scabra caused the
      highest depression in the deposited eggs, as they played a remarkable role as
      ovipositor deterrents. The majority of the plant extracts at 1% conc. could
      protect potato tubers at different intervals according to the calculated tuber
      damage index as follows: Iphiopna > Pithuranthos > Curcuma > Schinus (fruits)
      Thuja > Schinus (leaves) > Dodonaea > Citrullus. 

PMID- 23961037
TI  - Differential induction of chitinase in Piper colubrinum in response to
      inoculation with Phytophthora capsici, the cause of foot rot in black pepper.
AB  - Plant chitinases have been of particular interest since they are known to be
      induced upon pathogen invasion. Inoculation of Piper colubrinum leaves with the
      foot rot fungus, Phytophthora capsici leads to increase in chitinase activity. A
      marked increase in chitinase activity in the inoculated leaves was observed, with
      the maximum activity after 60 h of inoculation and gradually decreased
      thereafter. Older leaves showed more chitinase activity than young leaves. The
      level of chitinase in black pepper (Piper nigrum L.) upon inoculation was found
      to be substantially high when compared to P. colubrinum. RT-PCR using chitinase
      specific primers revealed differential accumulation of mRNA in P. colubrinum
      leaves inoculated with P. capsici. However, hyphal extension assays revealed no
      obvious differences in the ability of the protein extracts to inhibit growth of
      P. capsici in vitro. 

PMID- 23961038
TI  - Morphological characterization of the antennal sensilla of t he earwig Anisolabis
      maritima (Dermaptera: Carcinophoridae) with reference to their probable
      functions.
AB  - The earwig, Anisolabis maritima (Dermaptera: Carcinophoridae), is one of the most
      significant insects in KSA because, it was recorded in Saudi Arabia as a
      beneficial predator on eggs and newly hatched larvae of the red palm weevil,
      Rhyncophorus ferrugineus. We examined the external morphology of the antennal
      sensilla of males and females of A. maritima using scanning electron microscopy
      (SEM). The filiform antennae of A. maritima were of the conventional type
      comprising a basal scape, pedicle and a long, thread-like flagellum, which was
      composed of 12 flagellomeres of males and 16 flagellomeres of females. Six
      morphologically unique sensillar types were found and described on the antennae
      of males and females of A. maritima. Of those identified, there were three types
      of porous trichoid sensilla (long, curved and arcuate), and two types of
      basiconic sensilla (short and curved), and one type of aporous trichoid sensilla.
      The shape, external morphology and array of sensilla on the antennae of males and
      females of A. maritima were similar. 

PMID- 23961039
TI  - Chemical composition and antioxidant activities of Jeddah corniche algae, Saudi
      Arabia.
AB  - The increased use of natural product in the pharmaceutical industry has led to an
      increase in demand for screening for bioactive compounds in marine algae. An
      important economic algae, through chemical composition analysis and their
      antioxidant activities were investigated in this study. Chemical composition
      analysis of three algal samples from the Chlorophyta Ulva lactuca (U), Phaeophyta
      Sargassum crassifolia (S) and Rhodophyta Digenea simplex (D) was tested. Main
      components were sugars (57.40-185.13 mg/g dry weight), uronic acids (29.3-45.26
      mg/g dry weight), sulfate (94.7-181.2 mg/g dry weight), amino acids (7.6-16.7
      mg/g dry weight) and small amounts of betaines (2.38-8.47 mg/g dry weight).
      Hydrolyzed chemical composition analysis fractions of algal extract was shown a
      great proportion of sugars plus sulfate (as polysaccharide composed) ranges
      between 332 and 538.2 mg/g dry weight with trace amounts of uronic acids (?9%).
      All three algal extract showed antioxidant activities on lipoxygenase, DPPH and
      on Ames test. Two of aqueous extracts (U and D) inhibited lipoxygenase activity
      by less than 50%, where as the methanolic extract (S) caused 76% inhibition of
      the control. In all cases, the methanolic extract were more inhibitory than the
      aqueous extract. The (S) showed the highest antioxidant activity with DPPH (69%)
      in aqueous extract and in methanol extract with Ames test (85%). Both U and D
      showed antioxidant activity with DPPH in hexane by less of 25% where as in both
      aqueous and methanolic extracts by less than 50% of the control. Aqueous and
      methanolic extracts of U and D showed high inhibition by Ames test which caused
      70% and 75% respectively. IR spectra of algal extracts (U; D and S) range from
      1450 to 750 cm(-1) were very similar absorption band at 1430, 1370, 1250, 1130,
      1110, 1050 and 1020 cm(-1). Absorption bands were due to uronic acids, glucosides
      and sulfate. The presence of sulfated polysaccharide material in the fractions
      UF2, DF2 and SF2 were found as cell wall storage of marine algae, confirmed by
      (13)C NMR spectroscopy. It is concluded that the algal species probably have a
      different components and can be used in the activities of antioxidant enzymes as
      reduced the risks of enzymes. But the correlation between the chemical
      composition and antioxidant activities of algal extracts needs further
      investigation. 

PMID- 23961040
TI  - Effect of chlorpyrifos on healing of cutaneous leishmaniasis lesions after
      treatment with Pentostam((r)).
AB  - The insecticide chlorpyrifos (CPF) is widely used in the Kingdom of Saudi Arabia
      (KSA) to control agricultural pests. The present work is a preliminary
      investigation of the effect of CPF on healing of cutaneous leishmaniasis (CL)
      lesions, caused by Leishmania major in farmers exposed to this insecticide, after
      treatment with Pentostam((r)). Lesion diameters were measured and CPF
      concentrations in the blood plasma of farmer and non-farmer CL patients in Al
      Ahsa were detected by gas chromatography/mass spectrometry/mass spectrometry
      before and 6 weeks after treatment with Pentostam((r)). CPF concentrations in the
      blood of farmer patients ranged between 4.570 and 7.096 ng/MUl (mean = 6.19 +/-
      0.881 ng/MUl) before and after treatment with Pentostam((r)). The mean lesion
      diameter in these patients decreased by a factor of 2.21 after treatment with
      Pentostam((r)); they measured 1.85-11.75 mm, (mean = 6.165 +/- 3.500 mm) before
      treatment and 0.22-6.10 mm (mean = 2.796 +/- 2.102 mm) after treatment. Lesion
      diameter increased exponentially with the increase of CPF concentration in the
      patients' blood. CPF was not detected in the non-farmer patients before or after
      treatment. Their mean lesion diameter decreased by a factor of 6.86 after
      treatment with Pentostam((r)); they measured 1.33-7.10 mm (mean = 2.882 +/- 1.764
      mm) before treatment and 0.11-0.92 mm (mean = 0.425 +/- 0.277 mm) after
      treatment. The mean lesion diameter in farmer patients was much greater than that
      of non-farmer patients both before (2.14*) and after (6.657*) treatment with
      Pentostam((r)). Chronic exposure to low levels of the pesticide aggravates the
      development and delays the healing of CL lesions due to immunotoxicity and/or
      peripheral neurotoxicity caused by CPF. Further detailed studies would assess CPF
      effect on the severity of infection with CL in agricultural workers continuously
      exposed to this insecticide in different areas of KSA in conformity of their
      finding. 

PMID- 23961041
TI  - Phage typing, PCR amplification for mecA gene, and antibiotic resistance patterns
      as epidemiologic markers in nosocomial outbreaks of methicillin resistant
      Staphylococcus aureus.
AB  - Staphylococcus aureus is one of the major causes of community and hospital
      acquired infections. Bacteriophage considered as a major risk factor acquires S.
      aureus new virulence genetic elements. A total number of 119 S. aureus isolated
      from different specimens obtained from (RKH) were distinguished by susceptibility
      to 19 antimicrobial agents, phage typing, and PCR amplification for mecA gene.
      All of MRSA isolates harbored mecA gene, except three unique isolates. The
      predominant phage group is belonging to the (mixed group). Phage group (II)
      considered as an epidemiological marker correlated to beta-lactamase hyper
      producer isolates. MRSA isolates indicated high prevalence of phage group (II)
      with highly increase for phage types (O3A), which were correlated to the skin.
      Phage types (O80/O81) played an important roll in Community Acquired Methicillin
      Resistant S. aureus (CAMRSA). Three outpatients MRSA isolates had low
      multiresistance against Bacitracin (Ba) and Fusidic acid (FD), considered as
      CAMRSA isolates. It was detected that group I typed all FD-resistant MSSA
      isolates. Phage groups (M) and (II) were found almost to be integrated for
      Gentamycin (GN) resistance especially phage type (O95) which relatively increased
      up to 20% in MRSA. Tetracycline (TE) resistant isolates typed by groups (II) and
      (III) in MSSA. Only one isolate resistant to Sulphamethoxazole/Trimethoprim (SXT)
      was typed by (III/V) alone in MSSA. MRSA isolates resistant to Chloramphenicol
      (C) and Ba were typed by all groups except (V). It could be concluded that
      (PERSA) S. aureus isolates from the wound that originated and colonized, and
      started to build up multi-resistance against the topical treatment antibiotics.
      In this study, some unique sporadic isolates for both MRSA and MSSA could be used
      as biological, molecular and epidemiological markers such as prospective tools. 

PMID- 23961042
TI  - Histochemical changes of carbohydrate and protein contents in the digestive gland
      cells of the land snail Monacha cartusiana following starvation.
AB  - The present study was designed to investigate histochemically the detection of
      carbohydrate and protein in the normally feeding snails and after 15 and 30 days
      of starvation. Generally, abundant carbohydrate and protein materials were
      detected in the component cells of the digestive gland of normally feeding
      snails. The results of this investigation revealed a pronounced decline of
      carbohydrates in the digestive gland cells of Monacha cartusiana snails after
      starvation. Severe decline in carbohydrate content was observed especially after
      30 days of starvation. Moreover, protein inclusions have exhibited a week
      stainability in the digestive gland cells of these snails as a consequence of
      starvation. 

PMID- 23961043
TI  - Application of simple sequence repeat (SSR) markers for molecular diversity and
      heterozygosity analysis in maize inbred lines.
AB  - There is an important role of understanding the genetic diversity among and
      within inbred lines at the molecular level for maize improvement in different
      breeding programs. The present study was devoted to estimate the level of genetic
      diversity among the inbred lines of maize using the simple sequence repeat
      analysis (SSR). The application of six different SSR markers successfully
      provided the information on similarity or diversity as well as the heterozygosity
      of the allelic loci for all the eight inbred line of maize. 

PMID- 23961044
TI  - Blood parasites of livestock in certain Regions in Saudi Arabia.
AB  - Blood samples from camels, sheep, goats and cattle from six Regions in Saudi
      Arabia were examined for blood parasites. Asir Region camels were disinfected
      while those of the Eastern, Jazan, Northern Frontiers, Riyadh and Tabouk Regions
      were infected with Trypanosoma evansi (5-40%), those of Riyadh and the Eastern
      Regions were infected with Dipetalonema evansi (1-6%) and those of the Eastern,
      Jazan and Riyadh Regions were infected with Eperythrozoon species (8-20%). Sheep
      and goats of all tested regions were infected with Theilaria hirci (4-20% and 6
      14%, respectively), Theilaria ovis (5-19% and 6-24%, respectively) and
      Eperthrozoon ovis (2-9% and 2-8%, respectively). Sheep of the Eastern and
      Northern Frontiers Regions were also infected with Anaplasma ovis (2%) and also
      those of the Eastern Region were infected with Babesia motasi (4%) as well.
      Cattle of Asir and Eastern Regions were infected with Anaplasma marginale (1
      3.4%) and those of the Eastern, Jazan and Riyadh Regions were infected with
      Theileria annulata (11.3-25%) and Eperthrozoon wenyoni (1-4%). Moreover, Jazan
      cattle were infected with Babesia bigemina (6%) and a benign Theileria species
      (27%). Some of these parasites are recorded in new localities indicating that
      they are spreading in the country. Also, this is the first report in Saudi Arabia
      of D. evansi in camels, A. ovis and B. motasi in sheep and A. marginale and B.
      bigemina in cattle. These parasites may be introduced into the country with
      infected livestock infested with the vectors of these parasites. The suspected
      vectors of the detected parasites in Saudi Arabia is discussed. Follow up surveys
      of blood parasites are recommended to assess their distribution and infection
      rates in the livestock of all Regions of Saudi Arabia, to make plans for control
      measures against their vectors. 

PMID- 23961045
TI  - Effect of azadirachtin of neemix-4.5 on SWR/J mice.
AB  - Inbred normal SWR/J male and female mice, 8-10 weeks old and weighing 22.55-26.72
      g, were used throughout the study. A total of 100 males and 100 females were used
      and were divided into 20 groups, 10 animals in each group. Azadirachtin of neemix
      4.5, a commercial botanical pesticide derived from the neem tree, orally
      administered to male and female SWR/J mice at a dose level 9.0 mg/kg (1/10 LD50)
      for different treatment periods (2, 4, 6, 8 or 11.5 weeks) has produced signs of
      toxicity, mortality and changes in body and tissue weights of both sexes at
      almost all treated periods used in the present study. Moreover the oral
      administration of this dose level for 11.5 weeks has also resulted in some
      histopathological changes in the livers, kidneys and testes of treated animals
      compared with the control group, and the degree of these changes ranged from mild
      to severe in these organs of treated males. However, conflicting results have
      been reported concerning the toxicity of azadirachtin in mammalian species using
      different formulations of neem-based pesticides. It appears, therefore, that the
      toxicity produced by neemix-4.5 in the present study may be due to factors other
      than azadirachtin in this formulation. 

PMID- 23961046
TI  - Tabanidae (Diptera) of saudi arabia.
AB  - Samples were collected from southern, central and eastern regions of Saudi Arabia
      using Malaise traps and sweep nets. Nine species of Tabanidae were identified,
      two for the first time from Saudi Arabia, Hybomitra peculiaris (Szilady) and
      Atylotus pulchellus (Loew). Therefore, the total number of Tabanidae in Saudi
      Arabia is 31 species. Remarks of the species recorded in this study were given. A
      key to the genera of Tabanidae occurring in the Arabian Peninsula is also
      provided. Available literature for Saudi Arabian Tabanidae is summarized and
      provided. It is concluded that the tabanid fauna of Saudi Arabia is more similar
      to that of the Palaearctic region than to the Afrotropical region. 

PMID- 23961047
TI  - Changes induces by haloperidol (antidepressant drug) on the developing retina of
      the chick embryo.
AB  - Morphological and histological studies were done on the retina of chick embryos
      of 6th, 10th and 16th days of incubation by a single dose of haloperidol (0.25
      mg/egg), injected on day zero and 5 of incubation. To get an idea about the
      extent of the teratogenic effect of this drug on the development retina. Sign of
      malformation in the chick embryo after administration of haloperidol were seen as
      absent of the ear vesicles, eyes or decreased size of them. Retardation of growth
      of the retina at 6th, 10th and 16th days treated chick embryo were observed as
      evidenced of reduction of the size of the retina, associated with sign of
      degeneration of the retina cells. CONCLUSION: The injection of haloperidol drug
      give rise to several side effects as retardation of growth and degeneration of
      the cells. The decrease of the thickness of the layers and less density of the
      cells was related to direct effect of the drug on the cells of this organ. Also
      on the DNA formation and on the retardation of cellular mitotic activates,
      therefore the retina appeared decrease in thickness and less cell density with
      degeneration its cells.

PMID- 23961048
TI  - Efficacy of leaves extract of Calotropis procera Ait. (Asclepiadaceae) in
      controlling Anopheles arabiensis and Culex quinquefasciatus mosquitoes.
AB  - The present study aimed to investigate, the larvicidal, adult emergence
      inhibition and oviposition deterrent activity of aqueous leaves extract of
      Calotropis procera against Anopheles arabiensis and Culex quinquefasciatus as
      natural mosquito larvicide. The larvicidal activity was monitored against 2nd,
      3rd and 4th instar larvae of each mosquito species 24 h post-treatment. Adult
      emergence inhibition activity was tested by exposing 3rd instar larvae of each
      mosquito species to different concentrations of extracts (200, 400, 600, 800 and
      1000 ppm for An. arabiensis and 100, 200, 300, 400, 500 and 600 ppm for Cx.
      quinquefasciatus). Probit analysis was used to analyze data from bioassay
      experiments. The oviposition deterrent activity was tested by using three
      different concentrations of extracts (1000, 500 and 200 for An. arabiensis, and
      1000, 500 and 100 for Cx. quinquefasciatus) that caused high, moderate and low
      larval mortality in the larvicidal experiment against 3rd instar larvae. It was
      found that, LC50-LC90 values calculated were 273.53-783.43, 366.44-1018.59 and
      454.99-1224.62 ppm for 2nd, 3rd and 4th larval instars, respectively, of An.
      arabiensis and 187.93-433.51, 218.27-538.27 and 264.85-769.13 ppm for 2nd, 3rd
      and 4th larval instars, respectively, of Cx. quinquefasciatus. Fifty percent of
      adult emergence inhibition (EI50) was shown at 277.90 and 183.65 ppm for An.
      arabiensis and Cx. quinquefasciatus, respectively. The pupal stage was not
      affected till a concentration of 5000 ppm. The extract showed oviposition
      deterrence and effective repellence against both mosquito species at different
      concentrations, with the observation on that maximal eggs were laid in low
      concentration of extract. These results suggest that the leaves extract of C.
      procera possess remarkable larvicidal, adult emergence inhibitor, repellent and
      oviposition deterrent effect against both An. arabiensis and Cx.
      quinquefasciatus, and might be used as natural biocides for mosquito control. 

PMID- 23961049
TI  - Effect of nitrogen supply and Azospirillum brasilense Sp-248 on the response of
      wheat to seawater irrigation.
AB  - Response of wheat to Azospirillum brasilense Sp-248 inoculation with different N
      fertilizer levels using seawater irrigation was investigated. All inoculated
      treatments increased plant height, shoot and root dry weight, and tiller number
      in compared with uninoculated treatments. Yield parameters measured were also
      increased due to the inoculation. In terms of the effect of saline irrigation,
      there were no significant differences in growth and yield parameters in plants
      treated with tap water and others irrigated with 8.0% seawater concentration.
      This would indicate a relatively high tolerance of A. brasilense to saline
      irrigation and its ability to reduce the deleterious effects of saline on growth
      by increasing the plant's adaptation. However, increasing the seawater
      concentration in the irrigation water to 16.0% significantly decreased all tested
      parameters. Inoculation treatments generally increased NPKCa contents and
      decreased sodium ratio of the grains in compared with the uninoculated
      treatments. Overall results clearly revealed that the Azospirillum inoculation
      saved about 20 units of N-fertilizer and that saving was made economically
      feasible by decreasing the chemical fertilizers needed, improving the nitrogen
      content and counteracting the effects of salinity. 

PMID- 23961050
TI  - A report on the association of influenza B virus with respiratory tract infection
      of hospitalized children in Saudi Arabia.
AB  - Influenza viruses are recognized as one of the major causes of respiratory tract
      infection in young children and elderly people throughout the world. In this
      report, influenza B virus was detected when 200 clinical samples of
      nasopharyngeal aspirates, collected from hospitalized children aged from one
      month to three years with respiratory tract infections, were tested by Reverse
      Transcription Polymerase Chain Reaction (RT-PCR). PCR products on the conserved
      regions sequence of the non-structural gene identified the presence of influenza
      B virus in the clinical samples. This finding is important and it may become a
      real threat if not well considered. Due to massive mutations that influenza virus
      type B undergone, high protective measured should be taken. Therefore, further
      characterization and isolation of the virus are essentially needed. 

PMID- 23961051
TI  - Audit of stool analysis results to ensure the prevalence of common types of
      intestinal parasites in Riyadh region, Saudi Arabia.
AB  - The objective of the current study was to determine the incidence of common types
      of parasites encountered in the Central Region of Saudi Arabia. The current study
      is a retrospective study which includes the results of 10427 stool sample and
      occult blood sample. The results obtained during last two years (2005-2007), were
      compared to the earlier reports on parasites in the Central as well as other
      regions of Saudi Arabia. Attempts were made to find out the cases of increasing
      and/or decreasing trend of parasite incidence and to locate any differences
      between the current study results and the earlier reports. 

PMID- 23961052
TI  - Breeding biology aspects of spotted flapshell Turtle, Lissemys punctata (Lacepede
      1788), in Bangladesh.
AB  - This study was conducted to determine the breeding season, gonadal development,
      egg laying period, clutch size and other biological aspects of spotted flapshell
      turtle, Lissemys punctata, of Bangladesh between January 1997 and December 2001.
      The egg laying period of L. punctata, was found between August and March. The
      nesting sites were elevated fallow lands in secluded areas. The female turtle
      laid all the mature eggs at a time for each clutch at night. A gravid female
      turtle laid three clutches of eggs in each year and the mean clutch size was 13.0
      +/- 1.9 eggs and mean weight of each egg was 10.3 +/- 1.3 g. The eggs are
      spherical in shape and whitish in color. The mean incubation period was 173 +/-
      34 days (range 119-225 days). The incubation period of first clutch was the
      longest than the second and third clutches. Hatching success was found 41%.
      Maximum hatching was observed in June. The present investigation was made to
      explore the possibility to raise turtle farming in captive condition. The
      findings would, hopefully, help to rear the species and to assess the commercial
      potentiality of turtle farming in captive condition, that is, in the eco-climatic
      condition of Bangladesh. 

PMID- 23961053
TI  - Sporophyte and gametophyte development of Platycerium coronarium (Koenig) Desv.
      and P. grande (Fee) C. Presl. (Polypodiaceae) through in vitro propagation.
AB  - The sporophyte and gametophyte development of Platycerium coronarium and P.
      grande were compared through ex situ propagation using in vitro culture technique
      and under greenhouse and field conditions. The morphology of the sporophyte and
      gametophyte, type of spore germination and prothallial development of P.
      coronarium and P. grande were documented. Gametophytes of P. coronarium and P.
      grande were cultured in vitro using different media. The gametophytes were then
      transferred and potted in sterile chopped Cyathea spp. (anonotong) roots and
      garden soil for sporophyte formation. Sporophytes (plantlets) of the two
      Platycerium species were attached on the slabs of anonotong and on branches and
      trunks of Swietenia macrophylla (mahogany) under greenhouse and field conditions.
      Sporophyte morphology of P. coronarium and P. grande varies but not their
      gametophyte morphology. P. coronarium and P. grande exhibited rapid spore
      germination and gametophyte development in both spore culture medium and Knudson
      C culture medium containing 2% glucose. Gametophytes of P. coronarium and P.
      grande transferred to potting medium produced more number of sporophytes while
      the gametophytes inside the culture media did not produce sporophytes.
      Sporophytes of P. grande attached on mahogany branches produced more number of
      leaves with bigger leaf area than those attached on anonotong slabs. Likewise,
      sporophytes of P. coronarium attached on mahogany branches and anonotong slabs
      did not develop new leaves during two weeks monitoring and are still in a period
      of adjustment to its environment. Sporophytes of P. grande grown or attached on
      the trunk of mahogany trees in the field and under shaded environment favored
      their growth. 

PMID- 23961054
TI  - Effect of samh seeds supplementation (Mesembryanthemum forsskalei Hochst) on
      liver enzymes and lipid profiles of streptozotocin (STZ)-induced diabetic Wistar
      rats.
AB  - Thirty streptozotocin (STZ)-induced diabetic of Wistar Albino rats were divided
      into five groups. The rat groups received different food (natural diet or high
      fat content diet) supplemented with 10% or 15% of samh seeds for 6 weeks. At the
      end of the study, aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), alkaline phophatase (ALP) and lactate dehydrogenase (LDH) enzymes have
      been measured in diabetic rats liver. In addition, liver lipid profile (total
      cholesterol (TC), triglyceride (TAG), lipid peroxide production malondialdehyde
      (MDA)) and reduced glutathione (GSH) in have been measured in diabetic rats
      liver, and the levels of superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase (GPX) were also determined. The samh seeds diet
      supplemented with cholesterol significantly increase (P < 0.05) the levels of
      liver peroxide production MDA, TC and TG in diabetic rats comparing to the samh
      diet not supplemented with the cholesterol. However, the samh seeds significantly
      decrease (P < 0.05) the level of GSH. These data suggest that the samh seeds diet
      not supplemented with the cholesterol regulated C and TG metabolism and decrease
      the lipid peroxidation in the diabetic rats. 

PMID- 23961055
TI  - The role of caspase activation and mitochondrial depolarisation in cultured human
      apoptotic eosinophils.
AB  - Caspases are key intracellular molecules in the control of apoptosis, but little
      is known concerning their relative contribution to the cascade of events leading
      to eosinophil apoptosis. We examined caspase-3, -8, and -9 activities in receptor
      ligation dependent apoptosis induction in the cultured eosinophils (CE). CE
      cultured alone for 48 hours exhibited constitutive apoptosis (12% +/- 1.2).
      Significant (P < 0.05) enhancement of eosinophil apoptosis was observed following
      monoclonal antibody (Mab) treatment with CD45 (40% +/- 0.7), CD95 (36% +/- 1.6),
      or CD69 (34% +/- 0.2). Caspase activity was analysed using the novel CaspaTagTM
      technique and flow cytometry. CE ligated with CD45 (Bra55), CD95 (Fas) and CD69
      Mab resulted in caspase-3 and -9 activation after 16 hours post-ligation. This
      trend in caspase-3 and -9 activation continued to increase significantly through
      to the 20 and 24 hours time points when compared to isotype control. Activated up
      stream caspase-8 was detected 16 and 20 hours after treatment with CD45, CD95 and
      CD69 Mab followed by a trend toward basal levels at 24 hours. Ligation of CD95
      was followed by mitochondrial permeabilization, as demonstrated by marked
      increase in mitochondrial transmembrane potential ([Formula: see text]) at all
      time points. However, ligation with CD45 and CD69 failed to induce a change in
      [Formula: see text] at 16 hours post-treatment compared to isotype control even
      though there was an alteration in mitochondrial downstream-caspase activity
      following ligation with these Mab(s) at this time point. At 20 and 24 hours post
      ligation, CD45 or CD69 induce significantly altered levels of [Formula: see
      text]. Thus, the intrinsic and extrinsic caspase pathways are involved in
      controlling receptor ligation-mediated apoptosis induction in human eosinophils,
      findings that may aid the development of a more targeted, anti inflammatory
      therapy for asthma. 

PMID- 23961056
TI  - Safety and quality of some chicken meat products in Al-Ahsa markets-Saudi Arabia.
AB  - One hundred samples of 10 poultry meat products were collected from AL-Ahsa
      markets (Kingdom of Saudi Arabia). The samples were ranked from carcass cuts
      (chilled, frozen, fillet and thigh) to minced meat or further processed products
      as burger, nuggets, frankfurter and meat paste loaf. Samples were collected in
      triplicate for sensory, chemical and microbiological analysis to assure their
      quality and safety. The obtained results revealed variation in chemical
      composition; some products with high fat percentage had a high thiobarbituric
      acid value, which resulted in the appearance of an unacceptable flavor.
      Bacteriological analysis revealed that the mean total bacterial count was ranged
      from 2.7 * 10(4) cfu/g for nuggets(A) to 3.3 * 10(7) cfu/g for burger(B) and the
      other products in the range of 10(5)-10(6) cfu/g. While Staphylococcus aureus
      mean count ranged from less than 10(2) cfu/g for all samples, accept 10(4) and
      10(6) cfu/g for mince(B) and frankfurter samples, respectively. Escherichia coli
      isolated from 70% of the samples and Salmonella arizona was isolated at once from
      thigh samples. Thirty percentages of samples not comply with Saudi Standards due
      to sensory unacceptability and 21% of samples nonconforming with bacteriological
      specifications. 

PMID- 23961057
TI  - Phylogenetic analyses of peanut resistance gene candidates and screening of
      different genotypes for polymorphic markers.
AB  - The nucleotide-binding-site-leucine-rich-repeat (NBS-LRR)-encoding gene family
      has attracted much research interest because approximately 75% of the plant
      disease resistance genes that have been cloned to date are from this gene family.
      Here, we describe a collection of peanut NBS-LRR resistance gene candidates
      (RGCs) isolated from peanut (Arachis) species by mining Gene Bank data base. NBS
      LRR sequences assembled into TIR-NBS-LRR (75.4%) and non-TIR-NBS-LRR (24.6%)
      subfamilies. Total of 20 distinct clades were identified and showed a high level
      of sequence divergence within TIR-NBS and non-TIR-NBS subfamilies. Thirty-four
      primer pairs were designed from these RGC sequences and used for screening
      different genotypes belonging to wild and cultivated peanuts. Therefore, peanut
      RGC identified in this study will provide useful tools for developing DNA markers
      and cloning the genes for resistance to different pathogens in peanut. 

PMID- 23961058
TI  - The protective role of parsley extract against vincristine mutagenicity in
      Drosophila melanogaster.
AB  - In this study, Drosophila melanogaster males were treated with parsley plant
      extract and the anticancer drug vincristine (VCR) singly and in combined
      treatments (pre, co and post-treatments) to detect the mutagenic effects by using
      sex-linked recessive lethal test (SLRL) and estimation of cholinesterase enzyme
      (ChE) activities in order to compare the sensitivity of the two test systems. A
      wild type strain Oregon-R (Or-R) male flies of D. melanogaster were reared on a
      medium containing one concentration of each of VCR and parsley (4 ml/100 ml
      medium) in each single and combined treatment. Also the activity of ChE was
      estimated in some insects of the two generations: F1 females, F2 bar eye females
      (heterozygous) and F2 wild types males. The results indicate that both of parsley
      and vincristine did not cause significant increases of SLRL test in either the
      single or combined treatments. In contrast, estimation of ChE activities showed
      significant increase in all the broods within single and combination treatments,
      except female of the second generation of spermatid brood which treated with
      parsley and VCR at the same time. It is concluded that enzyme estimation is more
      sensitive than SLRL test for detection the mutagenic effect for parsley's extract
      and vincristine. 

PMID- 23961059
TI  - Antimicrobial activity and phytochemical analyses of Polygonum aviculare L.
      (Polygonaceae), naturally growing in Egypt.
AB  - Polygonum aviculare (Polygonaceae) is an herb commonly distributed in
      Mediterranean coastal regions in Egypt and used in folkloric medicine. Organic
      and aqueous solvent extracts and fractions of P. aviculare were investigated for
      antimicrobial activities on several microorganisms including bacteria and fungi.
      Phytochemical constituents of air-dried powered plant parts were extracted using
      aqueous and organic solvents (acetone, ethanol, chloroform and water).
      Antimicrobial activity of the concentrated extracts was evaluated by
      determination of the diameter of inhibition zone against both Gram-negative and
      Gram-positive bacteria and fungi using paper disc diffusion method. Results of
      the phytochemical studies revealed the presence of tannins, saponins, flavonoids,
      alkaloids and sesquiterpenes and the extracts were active against both Gram
      negative and Gram-positive bacteria. Chloroform extract gave very good and
      excellent antimicrobial activity against all tested bacteria and good activity
      against all tested fungi except Candida albicans. Structural spectroscopic
      analysis that was carried out on the active substances in the chloroform extract
      led to the identification of panicudine (6-hydroxy-11-deoxy-13 dehydrohetisane).
      Evaluation of the antimicrobial activity of panicudine indicated significant
      activity against all tested Gram-negative and Gram-positive organisms. Panicudine
      displayed considerable activity against the tested fungi with the exception of C.
      albicans. Antimicrobial activity of the extracts was unaffected after exposure to
      different heat treatments, but was reduced at alkaline pH. Studies of the minimum
      inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of
      panicudine on the tested organisms showed that the lowest MIC and the MBC were
      demonstrated against Salmonella paratyphi, Bacillus subtilis and Salmonella typhi
      and the highest MIC and MBC were against Staphylococcus aureus. 

PMID- 23961060
TI  - Effects of hyperoxia periodic training on free radicals production, biological
      antioxidants potential and lactate dehydrogenase activity in the lungs of rats,
      Rattus norvigicus.
AB  - Oxygen therapy has been widely used in lung injury (Li), adult respiraotory
      syndrome (ARDS) and inflammatory lung diseases as well as in mechanical
      ventilation in intensive care units. Exposure to hyperoxia is known to induct the
      production of reactive oxygen species (ROS) by mitochondria. Despite decades of
      research, the role of hyperoxia training in oxidative stress and ROS formation in
      the lungs is not known. The purpose of this study was to examine the effects of
      periodic-hyperoxia training on biological antioxidants (BAP) and lactate
      dehydrogenase (LDH) activities and free radicals (FR) production. Thirty adult
      male rats, matched with age and body weigh, were randomly assigned to three
      groups. The first group served as control (C) and the second (HP) was exposed to
      hyperoxia for 48. Animals in the third group (HP-T) were trained on hyperoxia for
      1.5 h daily for three weeks. Following the exposure period for each group animals
      were sacrificed and lungs tissues were homogenized for BAP, LDH and FR
      determinations. LDH activity was determined by Randox protocol (Randox - UK). BAP
      and FR were determined using dROM method (H&D - Italy). Results showed that mean
      (+/-SD) BAP activity increased significantly (p < 0.05) from the baseline control
      of 7105.88 +/- 2021.49 to 8611.20 +/- 1245.26 (U/L) after hyperoxia training;
      then dropped to 6784.00 +/- 1879.50 during hyperoxia exposure for 48 h. Whereas
      mean (+/-SD) FR production increased significantly (p < 0.05) from the baseline
      control of 262.50 +/- 67.52 to 339.90 +/- 64.84 during HP exposure for 48 h, then
      dropped to 211.13 +/- 52.05 (Carr), during HP training. Similarly, LDH activity
      increased significantly (p < 0.05) from the baseline control of 210.31 +/- 70.93
      to 339.90 +/- 64.84 during HP exposure for 48 h, then dropped to 159.30 +/-
      20.61(U/L), following HP-periodic training. Furthermore, the correlation (r =
      0.67*) of LDH on FR was significant (p < 0.05), implying that reduction in ROS
      generation induced by HP-periodic training is related to reduced rate of cell
      apoptosis caused oxidative stress. Based on the results of the present study HP
      periodic training is recommended in order to resist oxidative damage in the
      lungs. 

PMID- 23961061
TI  - Implications of fungal infections and mycotoxins in camel diseases in Saudi
      Arabia.
AB  - Natural feed ingredients (corn, barley and wheat bran) and compound feed
      (manufactured pellet) are two types of fodder used for animal feeding, especially
      camel in Saudi Arabia. Twenty samples of each type of fodder were collected from
      seven different regions and screened for the presence of fungi, aflatoxins,
      ochratoxin and zearalenone. Fungal isolation of natural feed ingredients yielded
      10 genera and 38 species of different fungi. Compound fodder samples were
      contaminated with 16 genera and 32 species of fungi. Total counts of Aspergillus,
      Penicillium and Fusarium in the animal feed samples were ranged from 54 to 223 *
      10(3), 31.9 to 60 * 10(3) and 18 to 29 * 10(3) CFU/g, respectively. These
      isolates when tested for aflatoxin, ochratoxin and zearalenone producing ability,
      revealed this property in only four isolate, identified as Aspergillus flavus, A.
      parasiticus, A. ochraceus and Fusarium graminaerum. The percentage of toxigenic
      fungi was ranged from 5.5% to 30% for natural feed ingredients and from 4.5% to
      20% for compound feed. The incidence of aflatoxins (AFT) in samples of natural
      feed ingredients was found to be ranged from 1 to 24.8 ppb, ochratoxin A (OTA)
      ranged from 1 to 44 ppb and zearalenone (ZON) ranged from 1 to 23 ppb.
      Contamination of compound feed with aflatoxin and ochratoxin A was ranged from 1
      to 6.4 ppb and 1 to 4.7 ppb, respectively. All samples collected were found
      contaminated with fungi or their toxins and natural feed samples were more
      contaminated compared to compound feed samples. The concentrations detected were
      in the allowed limit (<20 ppb) except four samples of natural feed ingredients
      which were above the allowed limit of the tested mycotoxins. In conclusion, feed
      samples were contaminated with fungi and some toxigenic isolates which were
      responsible about mycotoxin production. Some samples had exceeded amount of AFT,
      OTA and ZON and may be contaminated with other mycotoxins which mean implication
      of fungi in camel health problems and death in Saudi Arabia. 

PMID- 23961062
TI  - Effect of diets on growth, digestibility, carcass and meat quality
      characteristics of four rabbit breeds.
AB  - The current study was conducted to evaluate three diets using four rabbit breeds.
      A total of 320 male weaned rabbits representing four breeds named V-line, Saudi
      1, Saudi-2 and Saudi-3 were randomly distributed into three comparable dietary
      treatments. Three levels of indigenous feedstuffs (IFS) of 42.5%, 65% or 87.5%
      (alfalfa hay, barley and wheat bran) were substituted for the same levels of non
      indigenous feedstuffs in the diet (corn grain, soybean, molasses, and limestone)
      to form three diets named D1, D2 and D3, respectively. These dietary treatments
      were used to evaluate post-weaning growth performance, feed intake, feed
      conversion, carcass and lean composition, and nutrients digestibility in four
      rabbit breeds. Partial replacement of IFS with non-indigenous feedstuffs attained
      significant increase in growth performance. The diet containing 87.5% IFS led to
      significant increase in daily weight gains by 8.4, 4.0, 8.1, 6.2 and 6.7 g at age
      intervals of 5-6, 7-8, 9-10, 10-11 and 11-12 weeks compared to the control diet,
      respectively. The diet containing 87.5% IFS showed a significant reduction in
      feed conversion ratio compared to control diet during the experimental periods.
      The diet containing 65% IFS showed significant increases in pre-slaughter weight
      (112 g) and hot carcass weight (89 g), while dressing percent, offal weight and
      percent, and non-carcass weights and percentages (head, fur, legs + tail,
      viscera) were not significantly different. The diet containing 87.5% IFS gave an
      increase of 1.1%, 6.4%, 8.8%, 17.9%, 7.4%, and 19.6% in digestibility
      coefficients of organic matter (OM), crude protein (CP), neutral detergent fibre
      (NFD), acid detergent fiber (ADF), hemi-cellulose (HC) and cellulose (C) compared
      to control diet, respectively. Feed intakes were moderate and ranged from 69 to
      124 g for V-line, 77 to 128 g for Saudi-1, 79 to 130 g for Saudi-2, and 76 to 119
      g for Saudi-3 along with moderate ratios of feed conversion ranging from 2.65 to
      3.80, 2.45 to 3.90, 2.46 to 3.79 and 2.63 to 3.65, respectively. Pre-slaughter
      weight, hot carcass weight, and offal weight were in favour of Saudi-2 rabbits
      compared to the other groups. Both Saudi-1 and Saudi-2 rabbits were slightly
      higher than Saudi-3 in weights and percentages of head, fur, viscera and legs +
      tail. Lean and bone weights and percentages and meat to bone ratio in Saudi-2
      carcasses were slightly higher than those recorded in the other groups, while
      moisture, DM, CP, EE and ash contents in the lean have shown little differences
      between groups. Rabbits of Saudi-1 were ranked the first in digestibility
      coefficients of OM, CP, NDF, ADF, HC, C and cell count compared to other groups.
      Rabbits of Saudi-2 fed diet containing 87.5% IFS recorded the heaviest body
      weights and gains since this class showed considerable deviations in body weights
      of 345, 341, 269, 307, 321, 345 and 347 g at 6, 7, 8, 9, 10, 11 and 12 weeks of
      age, respectively, in comparison with the lightest class. Both Saudi-2 and Saudi
      3 rabbits fed the diet containing 87.5% IFS had favourable estimates of feed
      conversions ranging from 2.1 to 3.4, while rabbits of Saudi-1 fed the diet
      containing 87.5% IFS recorded the best digestibility coefficients. 

PMID- 23961063
TI  - Insecticide resistance of Culex pipiens (L.) populations (Diptera: Culicidae)
      from Riyadh city, Saudi Arabia: Status and overcome.
AB  - Three field populations of Cx. pipiens (L.) mosquitoes were collected from three
      different localities in Riyadh city. They were tested for developing resistance
      against commonly used insecticides to control mosquitoes in Riyadh. Two
      populations from Wadi Namar (WN1 and WN2) were highly resistant to deltamethrin
      (187.1- and 161.4-folds respectively). The field population from AL-Wadi district
      (AL-W) showed low resistance to lambda-cyhalothrin (3.8-folds) and moderate
      resistance to beta-cyfluthrin and bifenthrin (14- and 38.4-folds respectively).
      No resistance to fenitrothion was observed in WN1 population. Fenitrothion
      concentrations required to inhibit 50% of Acetylcholinesterase (AChE) activity in
      both WN1 population and the laboratory susceptible strain (S-LAB) were 0.073 and
      0.078 ppm respectively. Piperonyl butoxide suppressed resistance to pyrethroid
      insecticides (>90%) in field populations indicating that oxidases and/or
      esterases play an important role in the reduction of pyrethroids toxicity. These
      results should be considered in the current mosquitoes control programs in
      Riyadh. 

PMID- 23961064
TI  - Effect of endotoxin administration in pregnant camels.
AB  - Intravenous administration of Escherichia coli endotoxin at a dose of 0.05 MUg/kg
      bodyweight to pregnant camels resulted in abortion. The injection of endotoxin
      caused significant increases in the plasma concentration of 13,14-dihydro-15
      prostaglandin F2alpha, the metabolite of prostaglandin F2alpha (PG F2alpha) and
      cortisol and a significant decrease in the concentration of progesterone. It is
      suggested that endotoxin caused abortion in camels was a consequence of endotoxin
      induced PG F2alpha secretion resulting in luteal regression and decreased
      progesterone concentration. 

PMID- 23961065
TI  - Acute Taxol nephrotoxicity: Histological and ultrastructural studies of mice
      kidney parenchyma.
AB  - Taxol is a microtubule inhibitor drug widely used in treatment of many types of
      cancer. Nephrotoxicity is the most hazardous effect complicating chemotherapy in
      general and kidney functions must be monitored early during any chemotherapeutic
      course. The main objective of the present study was to investigate the effect of
      acute Taxol nephrotoxicity in mice. In the present study Taxol at different
      doses; MD, ID and MTD (0.6, 1.15 and 1.7 mg/kg), respectively, was given by intra
      peritoneal route to 54 adult male mice with an average body weight of 20-25 g.
      Kidney samples was taken 6, 24, 48 h following administration, fixed in 10%
      neutral buffered formalin, paraffin sections 5 MUm thick were stained by
      haematoxylin and eosin and PAS and then examined for histological changes.
      Samples from animals treated by the maximum dose (MTD = 1.7 mg/kg) for 48 h were
      fixed in 3% gluteraldehyde in phosphate buffer (pH 7.4) and processed for
      transmission electron microscope. Taxol given for short duration was found to
      produce marked degenerative changes in kidney parenchyma even in minimum
      tolerated dose (MD = 0.6 mg/kg). Individual variations were observed regarding
      the degree of nephrotoxicity. There was marked loss of renal tubules epithelial
      lining, damage of brush border and formation of hyaline casts within the damaged
      tubules. The alterations were in the form of both necrotic and apoptotic changes
      in the kidney tubules. Focal atrophy of glomerular tufts was also observed.
      Vascular congestion and degenerative changes in renal blood vessels were
      occasionally evident in some samples. Ultrastructure study revealed damage of
      glomerular membrane. Proximal tubule showed loss of basal infoldings, damage of
      brush border, mitochondrial degeneration and nuclear changes. Distal tubules also
      showed demarked degenerative changes. Increased frequency of micronuclei proved
      that Taxol had genotoxic effects in mice bone marrow cells. In conclusion Taxol
      had nephrotoxic effect on mice kidney that must be considered during its use as a
      chemotherapeutic agent in human. 

PMID- 23961066
TI  - Patient dose levels for seven different radiographic examination types.
AB  - This study was carried out as a part of a comprehensive project to establish a
      national diagnostic reference level (NDRL), for the first time, in Saudi Arabia.
      Seven of the most common X-ray examinations (10 projections) were included. This
      study consisted of 200 patients who were referred for X-ray examinations at King
      Khalid University Hospital (KKUH). The selected X-ray examinations were skull
      (PA), kub (AP and LAT), ankle (AP and LAT), foot (AP/OBL and LAT/OBL), hib (AP
      and LAT) and sinuses paranasal (AP). Mean patient information and exposure
      parameters for these seven radiographic examinations were recorded at KKUH. Some
      of these radiographic examinations were compared with their corresponding values
      at other national places [Security Forces Hospital (SFH); King Abdulaziz City for
      Science and Technology (KACST)] in Saudi Arabia. We found that the patient mean
      dose values recorded at KKUH were varied from those recorded at other national
      places. Wide variations in patient dose arising from a specific type of X-ray
      examination at different national places suggests that significant reductions in
      patient dose would be possible without affecting image quality. Furthermore,
      variations in patient dose may emerge from the examination technique, clinical
      condition, radiologist skill, tube current, tube potential and focus to film
      distance. The data of this study will be useful for the formulation of NDRLs, and
      it is also provides local diagnostic reference levels for some diagnostic X-ray
      examinations at KKUH and other national places in Saudi Arabia. 

PMID- 23961067
TI  - Floristic composition and vegetation analysis in Hail region north of central
      Saudi Arabia.
AB  - In this study, 19 sites representing different habitats in Hail region were
      regularly visited for two years, in each site 2-5 stands were selected for
      investigating floristic composition and vegetation types in the area. A total of
      124 species representing 34 families were recorded. The family Asteraceae is
      represented by the highest number of species (21 species) followed by the Poaceae
      (17 species) and the Brassicaceae (10 species) whereas, 15 families including
      Acanthaceae, Convolvulaceae, Moraceae, Nyctaginaceae and Primulaceae, are
      represented by a single species each. Chronological analysis of the vegetation in
      the area revealed the domination of Saharo-Sindian elements in the wild
      vegetations and of weedy species in the cultivated plots. Therophytes and
      chamaephytes are the dominating life forms of the vegetation spectra; therophytes
      represent 49.20% and chamaephytes represent 29.00% of the total species in the
      study area. Application of TWINISPAN and DECORANA classification and ordination
      techniques to the data produced seven vegetation groups. Ruderal habitats
      comprised two small groups A and F dominated by Phragmites australis and Imperata
      cylindrical (A), Euphorbia peplus and Sisymbrium irio (F), respectively. Two
      vegetation groups (B and G) have been recognized in the mountains and slopes
      dominated by Launaea mucronata, Trigonella stellata (B) and Ficus palmate and
      Fagonia bruguieri (G). Other two groups (C and E) inhabit the desert and
      mountainous wadies; these are represented by Gymnocarpos decandrus and Ochradenus
      baccatus (C) and Senecio glaucus subsp. coronopifolius and Rumex equisetiforme
      (E). On the other hand, one group (D) inhabits the cultivated plots and is
      represented by Plantago albicans and Rumex vesicarius, the last group also
      includes species restricted to the sand dune habitat of the Al-Nafud desert north
      of Hail city and represented by Calligonum polygonoides and Halyxolon
      salicornicum. The vegetation analysis indicated the invasion of Hail Flora by
      some foreign weeds such as Solanum nigrum, Lactuca serriola and Amaranthus
      lividus. The presence of these weeds points out the need to monitor the
      vegetation change in Hail region, and also other regions of Saudi Arabia, in
      order to elucidate the human impact on the wild plants diversity as human
      activities change with the fast development in the kingdom. 

PMID- 23961068
TI  - Hepatic tissue damage induced in Meriones ungliculatus due to infection with
      Babesia divergens-infected erythrocytes.
AB  - Babesia divergens is an intraerythrocytic parasite which is capable of infecting
      a wide range of vertebrates causing huge economic losses. Histopathological,
      hematological and biochemical changes during B. divergens infection in female
      Meriones ungliculatus were reported. Animals were challenged with 5 * 10(6) B.
      divergens-infected erythrocytes. Parasitemia were maximum at day 5 postinfection
      where all gerbils died. Infection of gerbils with Babesia induced a significant
      decrease in erythrocytic count as well as the hemoglobin concentration and
      hematocrit percentage but leucocytes were increased significantly when compared
      to uninfected gerbils. Liver enzymes aspartate aminotransferase (AST) and aniline
      aminotransferase (ALT) were significantly increased while albumin and total
      bilirubin were significantly decreased at day 5 postinfection with B. divergens
      infected erythrocytes. Histopathological scores of inflammation after infection
      of gerbils were done using Ischak's activity index and indicated that the liver
      was severely affected. In conclusion, the study indicated that the course of
      infection by B. divergens-induced alternations in hematology, biochemistry and
      histopathology of the hepatic tissue. 

PMID- 23961069
TI  - Genetic diversity among late blight resistant and susceptible potato genotypes.
AB  - RAPD polymerase chain reaction analysis was used to study the genetic diversity
      among a wild potato variety Solanum demissum (very resistant to late blight) and
      six potato cultivars (Hanna, Lady-Olympia, Lady-Rosetta, Spunta, Diamant and
      Cara) varied in their resistance to Phytophthora infestans. Cluster analysis of
      six potato genotypes showed that, all tested genotypes were separated into two
      clusters (1 and 2). Cluster 1, included only the wild potato variety (S.
      demissum), whereas cluster 2 divided into two groups (G1 and G2). Late blight
      high resistant cultivars Hanna and Cara were grouped in G1. Group 2 included the
      moderate resistant cultivar Spunta and the susceptible cultivars Diamant, Lady
      Rosetta and Lady-Olympia. The potato cultivars that showed highest genetic
      similarity to the wild potato variety were the resistant cultivars Hanna and
      Cara. Lowest genetic similarity was obtained with the susceptible cultivars Lady
      Rosetta, Diamant and Lady-Olympia. RAPD primer K17 yielded a band with molecular
      weight of 936 bp found in all susceptible potato cultivars (Lady-Rosetta, Lady
      Olympia and Diamant). On the other hand, band with molecular weight of 765 bp
      were detected in the wild potato and the resistant cultivars Hanna and Cara.
      Results of this study suggested that, the RAPD marker technique could be
      beneficial for revealing the genetic variability of different genotypes of potato
      varied in their resistibility to late blight. 

PMID- 23961070
TI  - Effect of Commiphora molmol on leukocytes proliferation in relation to
      histological alterations before and during healing from injury.
AB  - Myrrh, Commiphora molmol has been used as anti-inflammatory and wound healing
      commercial product. Leukocyte count had been reliable indicator for clinicians to
      monitor progress of healing for their patients. We hypothesized that myrrh
      supplement participate in the activation of leukocyte proliferation pathway prior
      and post skin injury and gastric ulcer. The purpose of the present study was to
      examine long-term effect of myrrh on leukocytes proliferation before injury and
      during different stages of healing. Results showed that all types of leukocytes
      were significantly (p < 0.05) higher in the myrrh-treated groups before and
      during healing. The pretreatment with myrrh offered a time-dependent rise in
      leukocytes proliferation. Microscopic examination of blood smear from myrrh
      treated rats with skin injury, showed an elevated count of middle-sized
      lymphocytes and neutrophils that were characterized with well-defined nuclear
      lobules and rich-granules cytoplasm. Furthermore, the microscopic examinations of
      the spleen and lymph nodes of myrrh-treated rats with skin injury, showed an
      increased thickness of lymphatic sheath around the arterioles in the white pulp
      that was associated with high density of the medium-sized lymphocytes in the
      secondary lymphoid follicles in the lymph nodes with engorged sinusoids. As myrrh
      enhanced leukocytes proliferation before injury, it can be concluded that myrrh
      posse's antigenic-driven responses and that indicated some foreignness or
      toxicity of some constituents of myrrh. Because myrrh helped to maintain the
      relative rise of leukocytes counts throughout healing period and that implied it
      activated late steps of both proliferation and differentiation pathways for all
      types of leukocytes during effective phase of the specific immune responses. 

PMID- 23961071
TI  - Genetical and biological control of cotton ashy stem caused by Macrophomina
      phaseolina in outdoor pot experiment.
AB  - Two outdoor pot experiments were carried out to evaluate the reaction of 11
      commercial Egyptian cotton cultivars Macrophomina phaseolina, the incitant of
      ashy stem in cotton and to evaluate the antagonistic ability of 27 isolates of
      Trichoderma sp. against pathogen cotton cultivars Giza 85, Giza 87, Giza 89 and
      Giza 90 were resistant to M. phaseolina because both survival and plant height of
      these cultivars was not affected when the soil was infested with the pathogen.
      None of the cultivars were found to be immune to highly pathogenic of M.
      phaseolina isolate. Of the 27 isolate's of Trichoderma that were evaluated, the
      best antagonistic performance was given by isolates nos. 2, 10, and 16 were
      promising for commercialization because they significantly increased survival and
      improved plant height and dry weight of the surviving cotton seedlings. 

PMID- 23961072
TI  - In vitro antagonism of cotton seedlings fungi and characterization of chitinase
      isozyme activities in Trichoderma harzianum.
AB  - The antagonistic fungus Trichoderma harzianum is widely recognized as a potential
      biocontrol agent against several soil-borne plant pathogens. T. harzinum is rich
      source of chitinoltic enzymes. In vitro screening of 5 isolates of T. harzinum,
      one isolate of Chaetomium globosum and one isolate of Conetherium mentance,
      revealed that all of them had reduced growth area of Macrophomina phaseolina,
      Fusarium solani and Rhizoctonia solani on PDA medium, significantly. The
      inhibition percentage ranged from 77.9 % to 55.9% for M. phaseolina and 59.2% to
      40.4% for R. solani by T. harzinum and C. mentance, respectively. Inhibition for
      F. solani ranged from 76.5% to 55.7% by T. harzinum and C. globosum,
      respectively. Isozyme gel electrophoresis was used to assess chitinase activity
      secreted by selected isolates of T. harzinum under different pH degrees and
      temperatures. Obtained results indicated that activity of chitinase isozyme
      produced at 30  degrees C was higher than 15-20  degrees C for all tested
      isolates and activity of chitinase produced by isolates No. 4 and 5 of T.
      harzinum at pH (7-7.5) was higher than at pH 6, respectively. 

PMID- 23961073
TI  - Antigenotoxic and anticytotoxic effect of camel milk in mice treated with
      cisplatin.
AB  - Camel milk (CM) has good nutritive value, in addition to its antigenotoxic and
      anticytotoxic effects. Therefore the aim of this investigation was to evaluate
      the capacity of CM to inhibit the micronucleated polychromatic erythrocytes
      (MnPCEs) in the bone marrow and improve the mitotic activity produced by
      cisplatin. Cisplatin is one of the most widely used antineoplastic drugs in the
      treatment of cancer. The 70 adult male Swiss albino mice were divided into seven
      groups:Gr. I: treated with distilled water and considered as a control group.Gr.
      II: treated with camel milk (33 ml/kg, b.w).Gr. III: treated previously with
      cisplatin (0.5 mg/kg, b.w).Gr. IV: treated with camel milk and followed after 2
      h. with cisplatin (33 ml/kg -> 0.5 mg/kg, b.w).Gr. V: treated with camel milk and
      cisplatin at the same time (33 ml/kg + 0.5 mg/kg, b.w).Gr. VI: treated with an
      acute single dose of cisplatin (2.5 mg/kg, b.w).Gr. VII: treated with camel milk
      prior and followed with an acute single dose of cisplatin (33 ml/kg -> 2.5 mg
      /kg, b.w). The animals were sacrificed 24 h after cisplatin injection. The
      pretreatment with CM dose caused a significant decrease (P < 0.001) in the
      frequency of MnPCEs and increase (P < 0.001) in the mitotic index (MI) induced by
      cisplatin when compared with the groups treated with cisplatin alone. The
      possible explanation for the antigenotoxic and anticytotoxic effects observed in
      the pretreatment with CM is ascribed to its contents. In conclusion, from the
      findings we suggest that this milk has some antioxidant effect, and the
      antigenotoxic mechanism of this milk needs to be explored further before their
      use during cisplatin chemotherapy. 

PMID- 23961074
TI  - Contamination of common spices in Saudi Arabia markets with potential mycotoxin
      producing fungi.
AB  - Fifteen spices obtained from common markets were examined for their mould
      profile. A total of 520 fungal isolates, representing 57 species, were recovered
      and identified from dried and ground spice samples on three different media using
      standard dilution plate method. The most heavily contaminated spice samples
      examined were observed in ginger in order of magnitude of 5325-6800 cfu/g. The
      most predominant fungal genera encountered were Aspergillus, Penicillium, and
      Rhizopus. Relative occurrence values of taxa disclosed ranged between 80% for
      Aspergillus flavus, Aspergillus niger and Penicillium arenicola, and 10% for some
      species. Samples obtained from sumac encountered very rare colony counts
      indicating its antifungal prosperities. The present magnitude of contamination
      and spectra of mycobiota approximate those reported for similar spice samples.
      Several potentially mycotoxigenic fungi were isolated from the majority of
      samples. The present study attracts the attention to potential risk for
      mycotoxins contamination may be caused as a result of using these spices,
      especially in great quantities. The study strongly recommends reduction in
      application of heavily contaminated spices like ginger in food processing and
      using some others like clove and sumac due to their antimicrobial properties. 

PMID- 23961075
TI  - Morphology of the egg shell and the developing embryo of the Red Palm Weevil,
      Rhynchophorus ferrugineus (Oliver).
AB  - The harvested eggs of Rhynchophorus ferrugineus are ovo-cylindrical shaped,
      averaged 1.09 mm in length and 0.43 mm in width, with ratio of [Formula: see
      text] 4.42. The chorionic layer of electron dense material is seen covering the
      exochorion structure of the eggs. The egg main body chorion exhibits a polygonal
      pattern and architecture surface of the egg is supported by a system of irregular
      interconnecting grooves. The micropylar apparatus of the eggs of the Red Palm
      Weevil, R. ferrugineus is described in the present study for the first time. Two
      micropylar openings are found closed to the center of the posterior wide pole of
      the egg. Each micropylar opening presents a single small orifice and its
      surrounding chorion is porous and densely set with tiny projections allowing the
      spermatozoa to penetrate the egg. Respiratory aeropyles are distributed on the
      borders of reticulations in the area chorionic surface of egg capsule. The
      hatching region is detected on the anterior part at the opposite side of the egg.
      Changes in the appearance and shape of R. ferrugineus eggs as well as the
      incidence of embryonic development are observed. 

PMID- 23961077
TI  - The origin of species without Darwin and Wallace.

PMID- 23961078
TI  - Estimation of BTEX in groundwater by using gas chromatography-mass spectrometry.
AB  - Advanced analytical modern technology such as coupling a gas chromatography to a
      mass spectrometric technique provides sufficient information to the environmental
      and analytical chemists to identify the presence of a variety of components of
      the specific volatile organic product, determine the degree of the product
      weathering and in some instances estimate the age of the product as well in the
      testing sample. In this study, we estimated BTEX in groundwater sample by using
      gas chromatography-mass spectrometry (GC-MS) after standardization of this
      technique for advancement towards purification check of water samples in the
      petro-polluted regions of the soil. 

PMID- 23961079
TI  - Correlation and Identification of Variable number of Tandem repeats of eNOS Gene
      in Coronary artery disease (CAD).
AB  - Endothelium-derived nitric oxide (NO) is synthesized from l-arginine by
      endothelial nitric oxide synthase (eNOS) encoded by the NOS3 gene on chromosome7.
      Since reduced NO synthesis has been implicated in the development of coronary
      atherosclerosis; polymorphisms of NOS gene might be associated with increased
      susceptibility to coronary artery disease (CAD). We therefore undertook this
      study to determine the association between the occurrence of CAD and eNOS4 b/a
      polymorphism in South Indian patients. We investigated the polymorphisms in the
      27 base-pair tandem repeats in intron4 of the eNOS gene in 100 unrelated CAD
      patients with positive coronary angiograms and 100 age and sex matched control
      subjects without any history of symptomatic CAD. The eNOS gene intron4 b/a VNTR
      polymorphism was analyzed by polymerase chain reaction. The plasma lipids levels
      and other risk factors were also determined. The genotype frequencies for
      eNOS4b/b, eNOS4a/b and eNOS4a/a were 63, 26 and 11 per cent in CAD subjects, and
      72, 20 and 8 per cent in control subjects, respectively. The genotype frequencies
      did not differ significantly between the two groups. The frequency of the a
      allele was 0.24 per cent in CAD subjects and 0.18 per cent in control subjects
      and no significant association was found between patients and control group (P =
      0.57, Odds ratio = 3.62). Plasma lipids, glucose and creatinine levels were
      significantly increased in CAD group. The genotypic frequencies and the allele
      frequency did not differ significantly between the CAD patients and controls
      indicating that this polymorphism was not an independent risk factor for the
      development of CAD in South Indian patients. 

PMID- 23961080
TI  - Thiocyclam does not induce structural chromosome aberrations in human lymphocytes
      in vitro.
AB  - Thiocyclam (trade name Evisect) is a broad-spectrum nereistoxin analogue
      insecticide used widely for agricultural applications. The aim of this
      investigation was to determine its genotoxic effects in the chromosome aberration
      (CA) test and determining of mitotic index (MI), using lymphocytes from
      peripheral blood samples of healthy human donors. A negative and a positive
      control (MMC) were also included. Chromosomal analyses of the metaphase plates of
      the samples treated with 14 different concentrations (from 0.1 to 120 MUg/ml) of
      thiocyclam, indicating the lack effect on chromosomes. Thus thiocyclam is not
      genotoxic but highly toxic on cell proliferation in human lymphocytes. 

PMID- 23961081
TI  - Influence of probiotic supplementation on blood parameters and growth performance
      in broiler chickens.
AB  - Effects of commercial probiotic (Bactocell(r)) on growth performance and blood
      parameters were evaluated. A total of 800 one day-old Ross broiler chicks were
      raised over 42 days. Chicks were wing-banded, weighed individually and randomly
      allocated into four equally major groups each having two replicates. Chicks of
      group 1 (control group) were fed the starter and finisher diets that did not
      supplemented with probiotic. The chicks of groups 2, 3, and 4 were fed the
      control starter and finisher diets supplemented with 1.6 g, 1 g and 0.8 g of
      probiotic per kg feed, respectively. Weekly body weight, feed consumption and
      feed conversion were measured. Blood parameters at 1, 4 and 6 weeks of age
      including packed cell volume (PCV), haemoglobin (Hb), total protein, albumin,
      total lipid and cholesterol were determined. All birds were kept under similar
      environmental, managerial and hygienic conditions. The results of the current
      study revealed that there was no significant change for Hb and PCV concentrations
      among different groups at all studied times. Also, total protein, lipids and
      albumin concentrations were not affected by probiotic supplementation. Chicken
      fed a diet containing various levels of probiotic showed a significant decrease
      (p ? 0.05) in cholesterol concentration compared to control group. Probiotic
      supplementation significantly increased the body weight and daily weight gain of
      broiler chicks at late ages (3-6 weeks). Also, the birds fed on probiotic levels
      1 and 0.8 g/kg diet exhibited higher body weight among chicken groups at 6 weeks
      of age. Improved feed conversion was noticed in birds fed a diet supplemented
      with probiotic. There was no significant difference in mortality rate among
      groups. We concluded that use of selected commercial probiotic resulted in
      improved performance parameters and reduced serum cholesterol in broiler
      chickens. Moreover, supplementation of the probiotic to broilers in the levels of
      1 and 0.8 g/kg diet was found to be better than control and 1.6 g/kg level
      indicating that increasing dietary probiotic level does not has the best
      performance. 

PMID- 23961082
TI  - Effect of age, pubertal stage and season on testosterone concentration in male
      dromedary camel.
AB  - The present study was conducted in the Laboratory of Animal Physiology and
      Biotechnology, Department of Animal Production, Faculty of Agriculture, Mansoura
      University, Egypt. The present investigation aimed at studying effects of ages,
      pubertal stages and seasons of the year on testosterone concentrations in blood
      plasma and tissue homogenate of the testes. The testes used in the current study
      were collected from a total of 104 one-humped male camels (Camelus dromedarius).
      Samples were taken from pre (1-3.5 years) and post (3.5-13 years) pubertal
      camels. Testes were studied for a two consecutive seasons. The freshly prepared
      homogenate of the testicular tissue and blood plasma were used for determining
      the concentrations of testosterone in plasma and testicular extract. The
      concentrations of testosterone in blood plasma and testicular tissue were
      significantly increased during the breeding season compared with that of non
      breeding season; the concentration of testosterone was higher in testicular
      tissue than in blood plasma. Testosterone concentrations in plasma and testicular
      tissue were increased in breeding than in non-breeding season. In addition, the
      testosterone concentrations were closely related with seasonal changes, stage of
      puberty and advancing age. 

PMID- 23961083
TI  - Effect of ovary preservation period on recovery rate and categories of dromedary
      camel oocytes.
AB  - The aim of this study was to evaluate the effect of different periods of ovary
      preservation at 25-30  degrees C for 5, 6, 7, 9, 12 and 24 h on recovery rate and
      oocyte categories of dromedary camel oocytes. Camel ovaries were collected from
      El-Bassatein slaughterhouse, Cairo. The collected ovaries were placed immediately
      after slaughtering into thermos in saline solution (0.9% NaCl) supplemented with
      antibiotics (100 IU penicillin and 100 MUg streptomycin/ml) at 25-30  degrees C
      and transported to the laboratory within 4-5 h. Ovaries were washed three times
      with warmed (30  degrees C) phosphate buffer solution (PBS) and one time with
      ethanol (70%). All visible follicles on the ovarian surface (2-8 mm in diameter)
      were counted. Oocytes were aspirated using a 20-gauge hypodermic needle. Oocyte
      yield was recorded and the number of oocytes/ovary was calculated. Oocytes were
      classified into five categories (compact, partial denuded, denuded, shrunken and
      cleaved oocytes). Results show that average number of follicles on each ovary was
      not significantly affected by preservation period, although tended to reduce only
      after 5 h of ovary preservation. However, this number was insignificantly reduced
      by increasing period of ovary preservation more than 5 up to 24 h. Average number
      of oocytes on each ovary was significantly (P < 0.05) reduced only between 5 and
      6 h of ovary preservation. Average number of oocytes showed higher reduction rate
      between 5 and 6 h from 12.4 to 9.3/ovary as well as between 9 and 12 h. Oocyte
      recovery rate showed insignificant decrease from 88.1% at 5 h to 78.6% at 9 h of
      preservation. However, it showed significant (P < 0.05) reduction to 62.0%
      between 9 and 12 h, then insignificantly decreased to 58.6 at 24 h of
      preservation of the ovaries. Frequency distribution and recovery rate of each
      category was the highest for compact oocytes and the lowest for cleaved oocytes
      at all periods of preservation. Increasing preservation period significantly (P <
      0.05) decreased frequency distribution of compact and cleaved oocytes, while
      increased frequency distribution of partial denuded, denude and shrunken oocytes.
      It might be concluded from the present results that the preservation of dromedary
      camel ovaries at 25-30  degrees C for 5-6 h was effective for maintaining the
      oocytes quality and recovery rate compared with the other preservation periods. 

PMID- 23961084
TI  - Deletion mutations in Duchenne muscular dystrophy (DMD) in Western Saudi
      children.
AB  - Duchenne and Becker muscular dystrophy (DMD and BMD) are caused, in the majority
      of cases, by deletions in the dystrophin gene (DMD). The disease is an X-linked
      neuromuscular diseases typically caused by disrupting (DMD) or non-disrupting
      (BMD) the reading frame in the dystrophin (DMD) gene. In the present study,
      amplifications of the genomic DNAs of unrelated 15 Saudi DMD males were carried
      out using multiplex polymerase chain reaction (PCR) for nine-hotspot regions of
      exons 4, 8, 12, 17, 19, 44, 45, 48 and 51. We detected six Saudi patients having
      deletions in a frequency of 40%. The frequency of deletions in exon 51 (20%) was
      the most common deletion frequently associated with our Saudi sample males. Exons
      19, 45, and 48 were present in a frequency of 6.7% each. All deletions were
      recognized as an individual exonic deletions, while no gross deletion where
      detected. Finally, the molecular deletions in the Saudi males was expected to be
      characterized by a moderate frequency among different populations due to the
      geographical KSA region, which it is in the crossroad of intense migrations and
      admixture of people coming from continental Asia, Africa, and even Europe. In
      conclusion, attempts to include an extra DNA samples might reflect a valid vision
      of the deletions within the high frequency deletion regions (HFDR's) in the DMD
      gene mutations in KSA. 

PMID- 23961085
TI  - Effect of different stress factors on some physiological parameters of Nile
      tilapia (Oreochromis niloticus).
AB  - This study was conducted to determine the effect of different stress factors on
      some physiological measurements of Nile tilapia (Oreochromis niloticus). A total
      number of 160 Nile tilapia, the body weight ranging between 100 and 120 g, were
      exposed to three stress factors of hypoxia, overcrowding and starvation for
      different periods 24, 72 and 144 h. The results of cortisol level were 134.15,
      144.27, 154.12 ng/ml and 140.18 ng/ml for control, hypoxia, overcrowding and
      starvation, respectively, while after 144 h did not show significant difference
      among treatments compared with control group. In contrast, the values of T3 and
      T4 observed reduction with significant difference that T3 ranged between the
      highest value 122.12 ng/ml for control group to lowest value of starvation group
      94.35, 93.81 and 88.46 ng/ml after 24, 72 and 144 h. Also, similar trend of
      results observed in T4 and blood glucose among treatments. And the enzymatic
      activity of lactate dehydrogenise (LDH) increased in hypoxic group, while a
      significant reduction appeared in overcrowding and starved fish compared to
      control group. The pyruvate kinase (PK) activity decreased in hypoxic group but
      increased in other group. 

PMID- 23961086
TI  - Development and hatching mechanism of Fasciola eggs, light and scanning electron
      microscopic studies.
AB  - Both light microscopy and scanning electron microscopy were used in the
      description. There were variable measurements of eggs from the same fluke and
      there was no relationship between the size of the fluke and size of eggs. Light
      microscopy revealed that the operculum has different shapes in Fasciola gigantica
      and F. hepatica. Under normal laboratory conditions of temperature (26 +/- 1 
      degrees C), miracidia of F. gigantica developed within 12-16 days period, but
      those of F. hepatica developed within a period of 13-15 days. The miracidia of F.
      gigantica measured 110 * 70 MUm and that of F. hepatica measured 136 * 74 MUm.
      The life span of the miracidium in F. gigantica ranged between 9 and 12 h, while
      in F. hepatica the life span did not exceed 10 h. Miracidial epidermal plates in
      miracidium of F. gigantica were found to be 20 plates arranged in four tiers of
      six, four, six and four. Hatching process was recorded using scanning electron
      microscope, and it indicated partially opened operculum. 

PMID- 23961087
TI  - Effect of water stress by Polyethylene Glycol 8000 and Sodium Chloride on
      germination of Ephedra alata Decne seeds.
AB  - Ephedra alata Decne is a perennial shrub and it is a very effective sand-binder.
      In Saudi Arabia, the species is associated with sand dunes formation, especially
      the mobile, non-saline and low moisture content ones. Its geographical
      distribution in Saudi Arabia includes the Northern, Eastern and Central regions.
      The aims of this study were to determine the effects of temperature, water
      potential and Sodium Chloride on germination of E. alata. Seeds were collected
      from King Khalid Centre of Wildlife Research and Development at Thumama (80 km
      north east of Riyadh), Saudi Arabia. Seeds were germinated at four alternating
      temperature regimes (8/22; 9/23; 13/27 and 18/35  degrees C). Seeds were also
      germinated under stress of aqueous Polyethylene Glycol (PEG) solutions mixed to
      create water potentials of 0; -0.3; -0.6; -1.2 and -1.5 MPa. Seed were also
      germinated in Sodium Chloride solutions of 0, 0.05, 0.1, 0.2 and 0.3 mol l(-1).
      Optimum germination was attained at 13/28  degrees C that corresponds to
      temperatures prevailing during spring time. Seeds germinated in Polyethylene
      Glycol solutions exhibited significantly lower germination than control
      especially when water potential fell below -0.3 MPa. Germination was also
      negatively affected by 0.1 mol l(-1) Sodium Chloride solution or above. Results
      indicated that the germination temperature responses of the nondormant seeds
      synchronize the event of germination with the season when environmental
      conditions are more favorable for subsequent growth and seedling establishment.
      Germination was also sensitive to both water potential and salinity. 

PMID- 23961088
TI  - Effect of breeding season and pregnancy status on serum progesterone, sodium,
      potassium, copper and iron of estrous synchronized Aradi goat does.
AB  - Eighteen out of 88 estrous synchronized Aradi goat does were randomly chosen to
      be bled during May-July (Out breeding season, n = 9) and during September
      December (Within breeding season, n = 9). Estrous synchronization was applied by
      using a control internal drug release (CIDR) as a reproductive management regimen
      throughout the year. Nineteen days after CIDR insertion, a 500 IU eCG was
      injected (i.m.) and CIDR was removed. Does were subjected to fertile bucks 48-60
      h after CIDR removal. Jugular blood samples were collected in non-heparinized
      Vacutainer tubes at 0 h just before CIDR insertion, every 3 days during CIDR
      insert, at day of CIDR removal, at incidence of estrus and mating, at day 1, 8
      and 30 post mating. Data on pregnancy were recorded and serum levels of
      progesterone (P), sodium (Na), potassium (K), copper (Cu) and iron (Fe) were
      determined. Progesterone concentration was higher (p < 0.05) within (2.85 +/-
      0.15 ng/ml) than outside (2.37 +/- 0.13 ng/ml) the breeding season. Pregnant does
      exhibited higher (p < 0.05) levels of progesterone (2.76 +/- 0.17 ng/ml) than non
      pregnant does (2.37 +/- 0.10 ng/ml). No significant interaction was found between
      season and pregnancy status on progesterone concentration. A typical progesterone
      profile was found during treatment days, as levels of P increased during CIDR
      insertion and declined at CIDR removal and thereafter. Neither breeding season
      nor pregnancy status affected Na(+) concentration. Contrariwise, mean levels of
      K(+) was higher (p < 0.05) outside (148.34 +/- 3.91 mg/L) than within (136.27 +/-
      3.91 mg/L) the breeding season. Pregnancy status did not influence K
      concentration. Sodium/potassium (Na(+)/K(+)) ratio was significantly (p < 0.01)
      higher within (30.29 +/- 0.44) than outside (27.62 +/- 0.44) the breeding season.
      On the contrary, pregnancy status did not affect this ratio. Iron concentrations
      neither affected by season nor pregnancy. Likewise, Cu concentrations were not
      affected by season, however Cu levels were higher (p < 0.05) in pregnant (147.75
      +/- 7.24 MUg/L) than in non-pregnant (127.31 +/- 5.03 MUg/L) does. 

PMID- 23961089
TI  - Dissolved nitrogen in drinking water resources in Al-Mahareth village of Assir -
      Saudi Arabia.
AB  - A water quality study was carried out on ground water wells, which serve as
      drinking water sources in farming communities in Al-Mahareth village of Assir
      region of the Kingdom of Saudi Arabia. The objective of this research was to
      determine concentrations of different forms of nitrogen in drinking water
      samples. Water samples were collected from these sources every 3 months (from
      January to December 2008) and analyzed for ammonia, nitrate and nitrite using the
      Plaintest Photometer Method. Results indicated that the annual mean concentration
      of nitrate, nitrite and ammonia varied from 23.09 to 25.06 mg/l, 0.006 to 0.36
      mg/l and 0.008 to 0.179 mg/l, respectively. An important observation was that, in
      general, higher nitrate and nitrite concentrations were found during the rainy
      season compared to the dry season. Concentrations of these potentially toxic
      substances were below WHO acceptable limits for surface and ground waters,
      indicating that these water resources appear safe for drinking from a dissolved
      nitrogen perspective. 

PMID- 23961090
TI  - Neurophysiological study on possible protective and therapeutic effects of Sidr
      (Zizyphus spina-christi L.) leaf extract in male albino rats treated with
      pentylenetetrazol.
AB  - In this study, anti-convulsant effect of Sidr leaf extract was examined by using
      pentylenetetrazol (PTZ) model on male albino rat by evaluating the changes in
      norepinephrine (NE), dopamine (DA) and serotonin (5-HT) contents in different
      brain regions (cerebellum, brainstem, striatum, cerebral cortex, hypothalamus and
      hippocampus). The administration of subconvulsive dose of PTZ (40 mg/kg i.p.)
      every other day for 9 days caused a significant decrease in monoamine content in
      different brain areas, this is may be due to the increase in nitric oxide levels,
      although antagonized the GABAA receptors which led to neurotransmitter release so
      the content is decreased. Administration of PTZ after treatment with Sidr (50
      mg/kg i.p.) leaf extract for 3 weeks as a protective group and administration of
      Sidr leaf extract for 3 weeks after treatment of PTZ as a therapeutic group
      caused significant increase in NE, DA, and 5-HT contents in all tested brain
      regions at most of the time intervals studied. This may be due to the presence of
      peptide and cyclopeptide alkaloids in the extract which inhibit neurotransmitter
      activity which led to the inhibition of neurotransmitter release. From these
      results, we can say that the Sidr leaf extract has neuroprotective and
      therapeutic roles against pentylenetetrazol convulsant effect. 

PMID- 23961091
TI  - Effect of Sclerotinia sclerotiorum on the disease development, growth, oil yield
      and biochemical changes in plants of Mentha arvensis.
AB  - Experiment was carried out to determine the effect of Sclerotinia sclerotiorum on
      the disease development, growth, oil yield and biochemical changes in the plants
      of Mentha arvensis. With the increase in initial inoculum levels of S.
      sclerotiorum a corresponding decrease in plant fresh and dry weights were
      recorded. The maximum reduction in the shoot-roots/suckers fresh weight and shoot
      roots/suckers dry weights (39.8%, 43.6%, 40.3% and 42.9%), respectively, was
      observed at the highest initial inoculum level of 12 g fungal mycelium/5 kg soil
      as compared to uninoculated control. The infection of roots and suckers due to S.
      sclerotiorum increased with increasing initial inoculum levels. At the lowest
      initial inoculum (1.0 g mycelium/5 kg soil), infection was observed 18.0% and at
      the highest (12 g mycelium/5 kg soil), it was 80.2%. Significant (P ? 0.01)
      reduction in oil yield, total chlorophyll, total phenol and total sugar content
      of M. arvensis plants was observed at the lowest inoculum level as compared to
      uninoculated control. 

PMID- 23961092
TI  - Influences of crude extract of tea leaves, Camellia sinensis, on streptozotocin
      diabetic male albino mice.
AB  - Natural remedies from medicinal plants are considered to be effective and safe
      alternative treatment for diabetes mellitus. The aim of the present study was to
      investigate the hypoglycemic activity of the crude tea leaves extract on
      streptozotocin (STZ)-induced diabetic mice. The average body weight of animals
      with diabetes and their percentage changes of body weight gain after 15 and 30
      days were significantly lower than that of the normal control mice. In diabetic
      mice, supplementation with tea leaves extract decreased the loss of body weight.
      After 15 and 30 days, significant increases in the levels of serum glucose,
      triglycerides, cholesterol, creatinine, urea, uric acid, glutamic pyruvic acid
      transaminase (GPT) and glutamic oxaloacetic acid transaminase (GOT) were noted in
      STZ-diabetic mice fed with normal diet. Also, the values of total protein in this
      group were statistically declined after 15 and 30 days. The levels of serum
      glucose and GPT were significantly elevated after 15 and 30 days in diabetic mice
      supplemented with tea leaves extract. Moreover, the level of serum GOT was
      notably increased after 30 days. Insignificant alterations were observed in the
      levels of serum triglycerides, cholesterol, total protein, creatinine, urea and
      uric acid in diabetic mice supplemented with tea leaves extract. Thus, the
      present results have shown that tea leaves extract has the antihyperglycemic,
      antihyperlipidemic, and antihyperproteinemic effects and consequently may
      alleviate liver and kidney damage associated with STZ-induced diabetes in mice. 

PMID- 23961093
TI  - Lack of micronuclei formation in bone marrow of rats after oral exposure to
      thiocyclam insecticide.
AB  - In this study, a nereistoxin analogue insecticide, thiocyclam, was administered
      to adult male albino rats by gavage dose of 135, 270 and 540 mg/kg b.w. repeated
      for 5 days at 24 h intervals. Control animals received only water. Thiocyclam was
      tested for its potential to cause genotoxic effects in rat bone marrow cells
      using an in vivo micronucleus assay. After 24 h of the last treatment, rats from
      all dose levels were sacrificed. Bone marrow cells were collected and assayed for
      the presence of micronuclei. Thiocyclam did not cause any increase in the
      incidence of micronucleated polychromatic erythrocytes in rats bone marrow at any
      of the dose levels. The polychromatic erythrocytes/normochromatic erythrocytes
      (PCE:NCE) ratio was found to be in the range from 0.50 +/- 0.11 to 0.55 +/- 0.02.
      The results of this study demonstrate that the effect of thiocyclam is not
      significant in the rat in vivo micronucleus assay. 

PMID- 23961094
TI  - Cytogenetic effects of sildenafil citrate (Viagra) on SWR/J mouse bone marrow
      cells.
AB  - The present study was conducted to investigate the cytogenetic effects of
      sildenafil citrate in SWR/J mouse bone marrow cells. Thirty-six males and 36
      females were used and divided into four groups. Each group contained 18 animals
      (9 males and 9 females), weighing 30-35 g. These animals were orally administered
      with a single dose of 13, 26 or 40 mg/kg sildenafil citrate solution. A control
      group received normal saline in an identical condition. The animals were
      sacrificed at 12, 24 or 48 h, after the treatment. Chromosome aberrations were
      investigated in 50 metaphases per animal. No significant differences in the
      percentages of mitotic indices or in the frequencies of chromosome aberrations
      were observed between treated male and female mice at any doses or at any time
      intervals used, therefore, data from the two sexes were pooled when analyzed
      statistically. No significant (p < 0.05) differences in the percentages of
      mitotic indices or in the frequencies of chromosome aberrations were observed
      between sildenafil citrate-treated groups and the control group at any doses or
      at any time intervals used. However, the percentages of centromeric adhesions
      increased significantly (p < 0.01) in treated groups as compared with the control
      group at all doses and at all time intervals used. In conclusion, the results of
      the present study suggest that sildenafil citrate does not have cytogenetic
      effects on mouse bone marrow cells, but the centromeric adhesions induced by this
      drug need further studies to confirm them and to investigate the possible
      mechanism(s) responsible for such effect. 

PMID- 23961095
TI  - Cultivation of different strains of king oyster mushroom (Pleurotus eryngii) on
      saw dust and rice straw in Bangladesh.
AB  - Pleurotus eryngii is a popular mushroom due to its excellent consistency of cap
      and stem, culinary qualities and longer shelf life. In Bangladesh, where
      Pleurotus mushrooms are very popular, P. eryngii may take position among the
      consumers, but currently this mushroom is not cultivated in large scale there. In
      this study, 3 strains of P. eryngii such as Pe-1 (native to Bangladesh), Pe-2
      (germplasm collected from China) and Pe-3 (germplasm collected from Japan) were
      cultivated on saw dust and rice straw and their growth and yield parameters were
      investigated. Pe-1 on saw dust showed the highest biological yield and efficiency
      (73.5%) than other strains. Also, the mycelium run rate and number of fruiting
      bodies were higher in Pe-1 than other two strains. The quality of mushroom
      strains was near about similar. On saw dust, the yield and efficiency were better
      than those cultivated on rice straw, however, on straw; the mushroom fruiting
      bodies were larger in size. This study shows the prospects of P. eryngii
      cultivation in Bangladesh and suggests further study in controlled environment
      for higher yield and production. 

PMID- 23961096
TI  - Two pathogenic species of Pythium: P. aphanidermatum and P. diclinum from a wheat
      field.
AB  - During a survey of pathogenic and non-pathogenic Pythium spp. in different
      localities in Egypt, several isolates of Pythia were obtained and maintained on
      corn meal agar. Among these isolates, Pythium aphanidermatum and Pythium diclinum
      were obtained from rhizosphere of wheat plants grown in Dear Attia village,
      Minia, Egypt. Identification was made using morphological and molecular analyses.
      P. aphanidermatum and P. diclinum were able to cause reductions in emergence and
      adulating in wheat in laboratory scale. P. aphanidermatum appeared to be the most
      aggressive parasite under agar and pot experimental conditions. 

PMID- 23961097
TI  - In vitro alpha-amylase inhibition and in vivo antioxidant potential of Amaranthus
      spinosus in alloxan-induced oxidative stress in diabetic rats.
AB  - Amaranthus spinosus Linn. (Amaranthaceae), commonly known as "Mulluharivesoppu"
      in Kannada, is used in the Indian traditional system of medicine for the
      treatment of diabetes. The present study deals with the scientific evaluation of
      alpha amylase and the antioxidant potential of methanol extract of A. spinosus
      (MEAS). The aim of this study was to investigate in vitro alpha-amylase enzyme
      inhibition by CNPG3 (2-chloro-4-nitrophenol alpha-d-maltotrioside) and in vivo
      antioxidant potential of malondialdehyde (MDA), glutathione (GSH), catalase (CAT)
      and total thiols (TT) in alloxan-induced diabetic rats of a methanolic extract of
      A. spinosus. Blood sugar was also determined in MEAS-treated alloxan-induced
      diabetic rats. MEAS showed significant inhibition of alpha-amylase activity and
      IC50 46.02 MUg/ml. Oral administration of MEAS (200 and 400 mg/kg) for 15 days
      showed significant reduction in the elevated blood glucose, MDA and restores GSH,
      CAT and TT levels as compared with a diabetic control. The present study provides
      evidence that the methanolic extract of A. spinosus has potent alpha amylase,
      anti-diabetic and antioxidant activities. 

PMID- 23961098
TI  - Hamiguitan Range: A sanctuary for native flora.
AB  - Hamiguitan Range is one of the wildlife sanctuaries in the Philippines having
      unique biodiversity resources that are at risk due to forest degradation and
      conversion of forested land to agriculture, shifting cultivation, and over
      collection. Thus, it is the main concern of this research to identify and assess
      the endemic and endangered flora of Hamiguitan Range. Field reconnaissance and
      transect walk showed five vegetation types namely: agro-ecosystem, dipterocarp,
      montane, typical mossy and mossy-pygmy forests. Inventory of plant species
      revealed 163 endemic species, 35 threatened species, and 33 rare species.
      Assessment of plants also showed seven species as new record in Mindanao and one
      species as new record in the Philippines. Noteworthy is the discovery of
      Nepenthes micramphora, a new species of pitcher plant found in the high altitudes
      of Hamiguitan Range. This species is also considered site endemic, rare, and
      threatened. The result of the study also showed that the five vegetation types of
      Mt. Hamiguitan harbor a number of endangered, endemic, and rare species of
      plants. Thus, the result of this study would serve as basis for the formulation
      of policies for the protection and conservation of these species and their
      habitats before these plants become extinct. 

PMID- 23961099
TI  - Determination of sugars in honey by liquid chromatography.
AB  - Honey is a rich conventional natural resource of sweetness and energy for human
      beings. A protocol for the determination of two important monosaccharide sugars
      (fructose and glucose) in honey was established in the current study by using
      normal phase partition liquid chromatography and 1-5% combined working standard
      of glucose, fructose and sucrose. 

PMID- 23961100
TI  - Bioefficacy of Aristolochia tagala Cham. against Spodoptera litura Fab.
      (Lepidoptera: Noctuidae).
AB  - Bioefficacy of leaf and root extracts of Aristolochia tagala Cham. at different
      concentrations was evaluated at room temperature against Spodoptera litura Fab.
      Effects on feeding, larvicidal and pupicidal activities and larval-pupal duration
      were studied. Higher antifeedant activity (56.06%), lethal concentration for
      feeding inhibition (3.69%), larvicidal (40.66%), pupicidal (28%), total mortality
      (68.66%) and prolonged larval-pupal duration (12.04-13.08 days) were observed in
      ethyl acetate leaf extract at 5.0% concentration. Dose dependant effect of test
      extracts was observed. This plant could be used to isolate active principles and
      to develop a new botanical formulation in pest management programmes. 

PMID- 23961102
TI  - Synergistic effect of kinetin and spermine on some physiological aspects of
      seawater stressed Vigna sinensis plants.
AB  - The effect of kinetin, spermine and their combination on growth vigor,
      photosynthetic pigments, some metabolites, some enzymes, polyamines and
      productivity of salt-stressed Vigna sinensis plants was investigated. Salt stress
      reduced all evaluated growth criteria and yield components of used plants.
      Chlorophyll (CHL (a, b, carotenoids, carbohydrates, protein, spermidine and
      spermine level as well as and amylase activity were also decreased in response to
      salinity. On the other hand, proline, K(+), Na(+) and putrescine concentration,
      and peroxidase activity were increased in the salt-stressed plants. Exogenous
      application of kinetin and spermine mitigated the deleterious effects of salinity
      stress on growth and yield of the used plants. Conversely, the combined treatment
      of kinetin and spermine induced additional reduction in growth and yield of the
      stressed plants, and the effect appeared to be constitutive. The protective
      effect of kinetin and spermine on V. sinensis plants appeared mainly due to the
      enhancement effect of these growth regulators on chlorophylls and protein content
      and polyamines titer. 

PMID- 23961101
TI  - Protective effect of l-carnitine against acrylamide-induced DNA damage in somatic
      and germ cells of mice.
AB  - Recent findings of acrylamide (AA) in many common foods have sparked renewed
      interest in assessing human health hazards. AA was evaluated by the International
      Agency for Research on Cancer as probably carcinogenic to humans. For this
      reason, the aim of this study is to evaluate the potential genotoxic effect of AA
      using chromosomal aberration analysis and micronucleus (MN) test in mouse bone
      marrow cells and morphological sperm abnormalities. The result of the present
      work indicated that treatment with a single dose of 10, 20, or 30 mg/kg b.wt. of
      AA for 24 h and the repeated dose of 10 mg/kg b.wt. for 1and 2 weeks induced a
      statistically significant increase in the percentage of chromosomal aberrations
      and micronuclei in bone- marrow cells. These percentages reduced significantly in
      all groups treated with AA and the protective agent l-carnitine. Also the results
      indicated that the dose 10, 20 and 30 mg/kg b.wt. of AA induced a statistically
      significant percentage of morphological sperm abnormalities compared with the
      control group. Such effect reached its maximum (7.24 +/- 0.61) with the highest
      tested dose which reduced to (4.02 +/- 0.58) in the group treated with the same
      dose of AA and l-carnitine. In conclusion, the results confirm the protective
      role of LC against the mutagenicity of AA. 

PMID- 23961103
TI  - Performance evaluation of three different types of local evaporative cooling pads
      in greenhouses in Sudan.
AB  - This study was conducted in Date Palm Technology Company Limited, Shambat,
      Khartoum State. To evaluate performance of three types of evaporative cooling
      pads for greenhouses (celdek pads, straw pads and sliced wood pads), as compared
      to the conditions outside the greenhouses (control), for pads. Performance
      evaluation includes environmental parameters (temperature and relative humidity
      at 8 am, 1 pm and 6 pm) and crop parameters (length and stem diameter, leaves
      number and width, fruit length and diameter, fruit weight and dry matter and
      yield). The results obtained for the temperature at 8 am showed that there was no
      significant difference (0.05) inside the greenhouses, while a high significant
      difference between the conditions inside and outside of the greenhouses was
      found. Significant differences were found at 1 pm and 6 pm between all treatments
      as compared to the conditions outside the greenhouses, and the results obtained
      for relative humidity showed high significant differences at 8 am and 1 pm inside
      the greenhouses and between inside and outside the greenhouse, respectively,
      while there was no significant difference at 6 pm inside the greenhouses and
      between inside and outside the greenhouses. On the other hand, the results
      obtained for crop parameters showed that there were significant differences
      between all parameters inside the greenhouses and outside the greenhouses;
      however, the greenhouses with sliced wood pads gave the highest yield and the
      greenhouses with straw pads gave the least and conditions outside gave the
      lowest. This study indicated that the sliced wood pads are better than the other
      evaporative cooling pads. 

PMID- 23961104
TI  - Economically and ecologically important plant communities in high altitude
      coniferous forest of Malam Jabba, Swat, Pakistan.
AB  - A study on the economically important plant communities was carried out during
      summer 2008 in various parts of Malam Jabba valley, Swat. The principal aim of
      the study was phytosociological evaluation with special reference to the
      occurrence of commercially important medicinal plant species in coniferous forest
      of the study area. Secondly to prepare ethnobotanical inventory of the plant
      resources of the area, as well as to evaluate the conservation status of
      important medicinal and aromatic plants (MAPs) through rapid vulnerable
      assessment (RVA) procedure. The study documented 90 species of ethnobotanical
      importance, out of these 71 spp used as medicinal plant, 20 spp fodder plant, 10
      spp vegetables, 14 spp wild fruit, 18 spp fuel wood, 9 spp furniture and
      agricultural tools, 9 spp thatching, fencing and hedges, 4 spp honey bee, 2 spp
      evil eyes, 2 spp religious and 3 spp as poison. Phytosociologically six plant
      communities were found, comprising five herbs-shrubs-trees communities and one
      meadow community. Further study is, therefore, required to quantify the
      availability of species and to suggest suitable method for their production and
      conservation. Recommendations are also given in the spheres of training in
      identification, sustainable collection, value addition, trade monitoring and
      cooperative system of marketing. 

PMID- 23961106
TI  - Consumption rate of some proteinic diets affecting hypopharyngeal glands
      development in honeybee workers.
AB  - The experiment was carried out under laboratory condition to study the
      consumption of some proteinic diets and their effect on hypopharyngeal glands
      (HPG) development during nursing period. The results showed that the bee bread
      and the pollen loads mixture with sugar (1:1) were more consumed by honeybee
      workers followed by Nectapol(r) and Yeast-Gluten mixture. The lowest consumption
      amount was recorded with traditional substitute. Clear differences were found in
      HPG development under feeding with different diets. The maximum development
      degree was observed when fed with bee bread followed by pollen loads and mixture
      from Yeast, Gluten and sugar (1:1:2). The acinal surface of HPG showed clear
      difference under feeding with difference diets. The largest area was recorded
      when honeybee workers fed on bee bread followed by Yeast-Gluten-sugar mixture
      (diet,4) and pollen loads(diet,2). 

PMID- 23961105
TI  - Antioxidant effect of vitamin E treatment on some heavy metals-induced renal and
      testicular injuries in male mice.
AB  - Toxic heavy metals in water, air and soil are global problems that are a growing
      threat to humanity. Heavy metals are widely distributed in the environment and
      some of them occur in food, water, air and tissues even in the absence of
      occupational exposure. The antioxidant and protective influences of vitamin E on
      a mixture of some heavy metals (Pb, Hg, Cd and Cu)-induced oxidative stress and
      renal and testicular injuries were evaluated in male mice. Exposure of mice to
      these heavy metals in drinking water for seven weeks resulted in statistical
      increases of plasma creatinine, urea and uric acid concentrations. The levels of
      glutathione (GSH) and superoxide dismutases (SOD) in kidney and testis tissues
      were significantly declined. Moreover, the histopathological evaluation of kidney
      and testis showed severe changes in mice treated with these heavy metals.
      Administration of vitamin E protected the kidney and testis of mice exposed to
      heavy metals as evidenced by appearance of normal histological structures,
      insignificant changes in the values of plasma creatinine, urea and uric acid, and
      the levels of kidney GSH and SOD, while the levels of testis GSH and SOD were
      notably decreased. These data suggest that the administration of vitamin E
      protects against heavy metals-induced renal and testicular oxidative stress and
      injuries. 

PMID- 23961107
TI  - Effect of ultraviolet radiation on chlorophyll, carotenoid, protein and proline
      contents of some annual desert plants.
AB  - Investigation was carried out to find whether enhanced ultraviolet radiation
      influences the Malva parviflora L., Plantago major L., Rumex vesicarius L. and
      Sismbrium erysimoids Desf. of some annual desert plants. The seeds were grown in
      plastic pots equally filled with a pre-sieved normal sandy soil for 1 month. The
      planted pots from each species were randomly divided into equal groups (three
      groups). Plants of the first group exposed to white-light tubes (400-700 nm) 60 w
      and UV (365 nm) 8 w tubes. The second group was exposed to white-light tubes (400
      700 nm) 60 w and UV (302 nm) 8 w tubes. The third group was exposed to white
      light tubes (400-700 nm) 60 w and UV (254 nm) 8 w tubes, respectively, for six
      days. The results indicated that the chlorophyll contents were affected by
      enhanced UV radiation. The chlorophyll a, b, and total contents were decreased
      compared with the control values and reduced with the enhanced UV radiation, but
      the carotenoid was increased compared with the control and also reduced with the
      enhanced UV radiation. So, the contents of chlorophylls varied considerably. M.
      parviflora showed the highest constitutive levels of accumulated chlorophyll a,
      b, and total chlorophyll (0.463, 0.307 and 0.774 mg g(-1) f w) among the
      investigated plant species. P. major showed the lowest constitutive levels of the
      chloroplast pigments, 0.0036, 0.0038 and 0.0075 mg g(-1) f w for chlorophyll a,
      b, and total chlorophyll at UV-365 nm, respectively. The protein content was
      decreased significantly in both root and shoot systems compared with the control
      values but, it was increased with increasing wave lengths of UV-radiation of all
      tested plants. R. vesicarius showed the highest protein contents among the
      investigated plants; its content was 3.8 mg g(-1) f w at UV-365 nm in shoot
      system. On the other hand, decreasing ultraviolet wave length induced a highly
      significant increase in the level of proline in both root and shoot of all tested
      plants. From the results obtained, it is suggested that proline can protect cells
      against damage induced by ultraviolet radiation. Statistically, the variations of
      the studied metabolic activities were significant due to UV radiation treatment
      in shoot and root system of all investigated plant species. 

PMID- 23961108
TI  - Taxonomic significance of trichomes micromorphology in cucurbits.
AB  - Studies on trichomes micromorphology using Scanning Electron Microscope (SEM)
      were undertaken in 23 species with one variety under 13 genera of the family
      Cucurbitaceae (viz., Benincasa hispida (Thunb.) Cogn., Citrullus lanatus (Thunb.)
      Matsum. & Nakai, Cucumis melo var. agrestis Naudin, Cucumis sativus L.,
      Diplocyclos palmatus (L.) C. Jeffrey, Edgaria dargeelingensis C.B. Clarke,
      Gynostemma burmanicum King ex Chakr., Gynostemma pentaphyllum (Thunb.) Makino,
      Gynostemma pubescens (Gagnep.) C.Y. Wu, Hemsleya dipterygia Kuang & A.M. Lu,
      Lagenaria siceraria (Molina) Standl., Luffa acutangula (L.) Roxb., Luffa
      cylindrica M. Roem., Luffa echinata Roxb., Melothria heterophylla (Lour.) Cogn.,
      Melothria leucocarpa (Blume) Cogn., Melothria maderspatana (L.) Cogn., Sechium
      edule (Jacq.) Sw., Thladiantha cordifolia (Blume) Cogn., Trichosanthes cucumerina
      L., T. cucumerina var. anguina (L.) Haines, Trichosanthes dioica Roxb.,
      Trichosanthes lepiniana (Naudin) Cogn. and T. tricuspidata Lour.). The trichomes
      in the family Cucurbitaceae vary from unicellular to multicellular, conical to
      elongated, smooth to ridges, with or without flattened disk at base and
      cyctolithic appendages, thin to thick walled, curved at apices to blunt.
      Trichomes micromorphology in the family Cucurbitaceae was found significant
      taxonomically. 

PMID- 23961109
TI  - Alleviation of drought stress of marigold (Tagetes erecta) plants by using
      arbuscular mycorrhizal fungi.
AB  - The effect of an arbuscular mycorrhizal fungus "AMF" (Glomus constrictum Trappe)
      on growth, pigments, and phosphorous content of marigold (Tagetes erecta) plant
      grown under different levels of drought stress was investigated. The applied
      drought stress levels reduced growth vigor (i.e. plant height, shoot dry weight,
      flower diameter as well as its fresh and dry weights) of mycorrhizal and non
      mycorrhizal plant as compared to control plant (non-drought stressed plant). The
      presence of mycorrhizal fungus, however, stimulated all growth parameters of the
      treated plant comparing to non-mycorrhizal treated plant. The photosynthetic
      pigments (carotene in flowers and chlorophylls a and b in leaves) were also
      stimulated by the mycorrhizal fungi of well-watered as well as of water-stressed
      plants. The total pigments of mycorrhizal plants grown under well-watered
      conditions were higher than those of non-mycorrhizal ones by 60%. In most cases,
      drought-stressed mycorrhizal plants were significantly better than those of the
      non-mycorrhizal plants. So, the overall results suggest that mycorrhizal fungal
      colonization affects host plant positively on growth, pigments, and phosphorous
      content, flower quality and thereby alleviates the stress imposed by water with
      holding. 

PMID- 23961110
TI  - Effects of Melothria maderaspatana leaf extract on antioxidant status in sham
      operated and uninephrectomized DOCA-salt hypertensive rats.
AB  - The present study was designed to investigate the antihypertensive and
      antioxidant effect of Melothria maderaspatana leaf extract (MME) on sham-operated
      and DOCA-salt (deoxycorticosterone acetate) induced hypertensive rats.
      Administration of DOCA-salt significantly increased the systolic (from 127 to 212
      mm Hg) and diastolic (from 91 to 174 mm Hg) blood pressure compared to sham
      operated control rats, while treatment with MME significantly reduced the
      systolic (from 212 to 135 mm Hg) and diastolic (from 174 to 96 mm Hg) blood
      pressure compared to hypertensive control. In DOCA-salt rats, the plasma and
      tissue concentration of thiobarbituric acid reactive substances (TBARS) and lipid
      hydroperoxide (LOOH) significantly increased and administration of MME
      significantly reduced these parameters towards the levels in sham-operated
      control. In hypertensive rats, activities of the enzymatic antioxidants such as
      superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and
      levels of non-enzymatic antioxidants such as vitamin C, vitamin E and reduced
      glutathione (GSH) decreased significantly in the plasma and tissues.
      Administration of MME returned the enzymatic and non-enzymatic antioxidants
      towards sham-operated control. MME shows both antihypertensive and antioxidant
      properties in DOCA-salt hypertensive rats and, among the three different doses
      tested, 200 mg/kg caused the maximum effect. 

PMID- 23961111
TI  - Association between beta+252 tumour necrosis factor polymorphism and asthma in
      western Saudi children.
AB  - There is strong evidence that supports the role of tumour necrosis factors (TNF
      alpha/beta) as common genetic factors, located on 6p21.1-6p21.3 loci, in the
      pathogenesis of asthma disease. In this study, we extended our research work on
      TNFA to include the genotyping of Saudi asthmatic children as regards to TNFB
      gene (namely as lymphotoxin-alpha, LTA). We examined 60 asthmatic Saudi children
      compared to 56 healthy non-asthmatics using the PCR-RFLP analyses to identify the
      polymorphism +252A>G in intron 1 in lymphotoxin-alpha gene. We identified 55% of
      the allele A of the LTA*NcoI polymorphism in subjects with asthma disease, and
      45% of the allele G. In this study, the frequency of the LTA*NcoI-A/A genotype
      was 40% preferably to the LTA*NcoI-G/A and LTA*NcoI-G/G genotypes. In addition,
      the severe persistent asthmatic cases were associated with the LTA*NcoI-AA
      genotype at a frequency of 80%, while the genotype LTA*NcoI-GG are associated
      with the mildest form of the disease. Consequently, one could predict the
      severity of asthma and hence the polymorphism of the LTA*NcoI. Herein, we stated
      that more than 93% of Saudi children under investigation lived in the randomized
      areas of western regions of Saudi Arabia. In conclusion, genotype frequencies for
      the LTA+252 polymorphisms were significantly different from the controls. These
      findings may have implications for future early intervention studies by helping
      to identify infants at increased risk for wheezing and childhood asthma. 

PMID- 23961112
TI  - Effect of honeybee race and worker age on development and histological structure
      of hypopharyngeal glands of honeybee.
AB  - Development of hypopharyngeal glands (HPG) of native honey bee workers (Apis
      mellifera jemenitica) and Carniolan hybrid bees reared under normal constipations
      was studied. The HPG development degree and acini surface were influenced with
      age. The development degrees increased gradually. The maximum developmental
      degree was recorded at 9-days old in both two races. The development decreased
      after 12 days. The HPG development degree and acini surface of all ages in native
      bees were significantly less than Carniolan hybrid bees. Histological studies on
      HPG showed that there were some differences between the glands of the two races
      at the maximum developmental stage (9-days). The staining of cell cytoplasm by
      haematoxylin and eosin was similar. However secretory cells numbers were more in
      Carniolan hybrid than the native one. 

PMID- 23961113
TI  - Keratinolytic activity of purified alkaline keratinase produced by Scopulariopsis
      brevicaulis (Sacc.) and its amino acids profile.
AB  - Sodium dodecyl sulfate-polyacrlyamide gel electrophoresis (SDS-PAGE) was used to
      assess the purity and molecular weight of the previously purified alkaline
      keratinase enzyme of Scopulariopsis brevicaulis. The enzyme was homogenous, as
      seen by a single band of protein, and had an apparent molecular weight of 28.5
      kDa. Amino acid profile of the purified keratinase revealed that it was composed
      of 14 different amino acids with high proportions of glutamic acid (20.86%),
      alanine (14.52%), glycine (14.21%), leucine (8.59%) and serine (7.81%). The
      enzyme contained moderate amounts of valine (6.01%), threonine (5.58%) and phenyl
      alanine (5.22%). The purified enzyme of S. brevicaulis exerted a potent
      keratinolytic activity and was capable to hydrolyze different keratinaceous
      materials with highest activity on chicken feathers followed by human nails and
      human hair. 

PMID- 23961114
TI  - Studies on genetic diversity among populations of Persicaria barbata (L.) H. Hara
      from India based on internal transcribed spacer sequences of nuclear ribosomal
      DNA.
AB  - Internal transcribed spacer (ITS) region of nuclear ribosomal DNA from 16
      populations of Persicaria barbata (L.) H. Hara (Polygonaceae) belonging to five
      geographical locations of India (Arunachal Pradesh, Himachal Pradesh, Bihar,
      Karnataka and Andaman Island) was sequenced. Analysis of nucleotide sequences
      reveals polymorphism among the populations. UPGMA analysis conducted on the ITS
      datasets shows that the sampled populations of P. barbata are grouped according
      to their geographic locations and are supposed to be evolved under reproductive
      isolation which most probably are due to the long distance distribution and
      population fragmentation. 

PMID- 23961115
TI  - Antifeedant and larvicidal activities of Rhein isolated from the flowers of
      Cassia fistula L.
AB  - Antifeedant and larvicidal activities of rhein (1,8-dihydroxyanthraquinone-3
      carboxylic acid) isolated from the ethyl acetate extract of Cassia fistula flower
      were studied against lepidopteron pests Spodoptera litura and Helicoverpa
      armigera. Significant antifeedant activity was observed against H. armigera
      (76.13%) at 1000 ppm concentration. Rhein exhibited larvicidal activity against
      H. armigera (67.5), S. litura (36.25%) and the LC50 values was 606.50 ppm for H.
      armigera and 1192.55 ppm for S. litura. The survived larvae produced malformed
      adults. 

PMID- 23961116
TI  - Developmental toxicity of orally administered sildenafil citrate (Viagra) in
      SWR/J mice.
AB  - Normal adult inbred SWR/J mice were used to investigate the teratogenic and other
      possible toxic effects of various dose levels of sildenafil citrate (Viagra) on
      fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of
      sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3,
      4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into
      pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy,
      all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity)
      and for external, internal and skeletal malformations. A total of 285 pregnant
      mice were used in the present study. None of the dams treated with sildenafil
      citrate at any of the oral dose levels used in the present study died during the
      experimental period and all dams treated with the drug failed to reveal overt
      signs of maternal toxicity. Moreover, the results of the present study clearly
      demonstrate that none of the multiple oral dose levels of the drug at any time
      interval used has induced any external, internal or skeletal malformations in the
      fetuses obtained from treated females. However, the dose level of 40 mg/kg body
      weight of sildenafil citrate has a growth suppressing effect on alive fetuses
      when it was administered at all the time intervals used in the present study.
      Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo
      fetal toxicity when the drug is applied on days 13-15 of gestation. The possible
      mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing
      effects of sildenafil citrate were discussed. The results of this study have
      important implications for the widespread use of this drug. 

PMID- 23961117
TI  - Assessment of local management practices on the population ecology of some
      medicinal plants in the coniferous forest of Northern Parts of Pakistan.
AB  - A study on the assessment of local management practices on the population of
      three medicinal plants viz.: Persicaria amplexicaule. D. Don., Valeriana
      jatamansi Jones and Viola serpens Wall ex Roxb was conducted during 2002-2004 in
      the coniferous forest of Northern Parts of Pakistan. The objective of the study
      was to know the impact of current management practices on the population size of
      targeted plants. The study showed that the involvement of locals in the gathering
      of targeted plants varied with the change in elevation. Among the targeted plants
      V. serpens was collected by large majorities of people (83.3%) at 2700 m followed
      by 72% at 2300 m and 37% at 1900 m. V. jatamansi was harvested by a small number
      of people (18.1%) at 1900 and 2300 m each, followed by 8.3% at 2700 m. While P.
      amplexicaule was harvested by a few collectors (9.1%) at 1900 m and 9.6% at 2300
      m followed by 8.3% at 2700 m. The study concluded that these species have been
      extracted so heavily in the past that they are found now sparsely in some sites
      of the study area. Secondly, due to loss of its habitat by deforestation and
      encroachment of land for cultivation its population is on the decline towards
      extinction. Therefore, the current study recommends the conservation of the
      remaining populations of targeted plants through active participation of local
      communities. 

PMID- 23961118
TI  - Toxoplasma gondii: Ultrastructure study of the entry of tachyzoites into
      mammalian cells.
AB  - Toxoplama gondii (Apicomplexa: Coccidia), an obligatory intracellular parasite
      with a unique capacity to invade virtually all nucleated cell type from warm
      blooded vertebrate hosts. Despite the efficiency with which Toxoplasma enters its
      host cell, it remains unresolved if invasion occurs by direct penetration of the
      parasite or through phagocytosis. In the present work, electron microscopic study
      was designed to examine the entry process of Toxoplasma (RH strain) into
      macrophages and non phagocytic-host cells (Hela cells) and to observe the
      ultrastructure changes associated with intracellular parasitism. The results
      showed that both active invasion and phagocytosis were occurred and revealed that
      invasion is an ordered process that initiates with binding of the parasite at its
      apical end followed by tight-fitting invagination of the host cell membrane and a
      prominent constriction in the parasite at the site of penetration. The process
      ended by the professional parasitophorous vacuole that is distinct at the outset
      from those formed by phagocytosis in which once Toxoplasma triggered, phagocytic
      uptake can proceed by capture of the parasite within a loose fitting vacuole
      formed by localized membrane ruffling. The cytopathic effects of the parasite on
      macrophages and Hela cells were demonstrated within 5-15 h post-inoculation in
      the form of degenerative mitochondria, swelling Golgi apparatus and widening of
      endoplasmic reticulum indicating intracellular oedema. These changes were
      exaggerated and several cells were found dead after 48-72 h. 

PMID- 23961119
TI  - Bioreduction of Cr(VI) by alkaliphilic Bacillus subtilis and interaction of the
      membrane groups.
AB  - Detoxification of Cr(VI) under alkaline pH requires attention due to the alkaline
      nature of many effluents. An alkaliphilic gram-positive Bacillus subtilis
      isolated from tannery effluent contaminated soil was found to grow and reduce
      Cr(VI) up to 100% at an alkaline pH 9. Decrease in pH to acidic range with growth
      of the bacterium signified the role played by metabolites (organic acids) in
      chromium resistance and reduction mechanism. The XPS and FT-IR spectra confirmed
      the reduction of Cr(VI) by bacteria into +3 oxidation state. Chromate reductase
      assay indicated that the reduction was mediated by constitutive membrane bound
      enzymes. The kinetics of Cr(VI) reduction activity derived using the monod
      equation proved (K s = 0.00032) high affinity of the organism to the metal. This
      study thus helped to localize the reduction activity at subcellular level in a
      chromium resistant alkaliphilic Bacillus sp. 

PMID- 23961120
TI  - Histological alterations and biochemical changes in the liver of sheep following
      Echis coloratus envenomation.
AB  - Snake envenoming is a major problem in Al-Jouf Province of Saudi Arabia where
      most of these envenoming are caused by Echis coloratus which is the highest risk
      to human and animals in this Province. Little, if any, has been carried out on
      the histological alterations and biochemical changes in the liver of sheep
      following snake envenomation. Healthy adult male Ovis orientalis sheep were
      subjected to E. coloratus envenomation in an attempt to evaluate the histological
      alterations and biochemical changes in the liver. E. coloratus venom elevated
      glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      triglyceride and total bilirubin while cholesterol was reduced. The histological
      alterations were mainly pyknosis, karyorrhexis, cytoplasmic vacuolation,
      necrosis, fatty changes and hepatocytes atrophy. Sinusoidal dilatation, Kupffer
      cell activation, amyloidosis, portal vein thrombosis, partial glycogen depletion
      and hepatic architecture distortion were also detected. The findings revealed
      that E. coloratus venom produced biochemical changes and histological alterations
      in the liver of the envenomated sheep that might affect the functions of this
      organ severely. 

PMID- 23961121
TI  - Determination of heavy metals in the fruit of date palm growing at different
      locations of Riyadh.
AB  - Exposure of heavy metals to human beings has risen dramatically in the last 50
      years. In today's urban and industrial society, there is no escaping from
      exposure to toxic chemicals and heavy metals. Humans are more likely to be
      exposed to heavy metal contamination from the dust that adheres to edible plants
      than from bioaccumulation. This is because it is very difficult to wash off all
      the dust particles from the plant material before ingesting them. The objectives
      of this experiment were to determine the concentrations of lead (Pb) and cadmium
      (Cd) in washing residues and in the tissues of fruits of date palm growing in 14
      sites of Riyadh and also to assess whether the fruits were safe for human
      consumption. The washing residues and tissue of date palm fruits collected from
      different sites showed the presence of significant amounts of the Pb and Cd. The
      concentration of Pb in the dust and fruit tissue increased with increasing
      anthropogenic sources. Therefore, fruits of date palm might be used as a
      pollution indicator; it might be recommend that fruits of date palm could be safe
      for human consumption after washing. The mean concentration of Pb and Cd in all
      the samples collected from different sites is within the safe limits recommended
      by FAO/WHO. 

PMID- 23961122
TI  - Protection of human erythrocyte using Crinum asiaticum extract and lycorine from
      oxidative damage induced by 2-amidinopropane.
AB  - The intention of this investigation was to evaluate the free radical scavenging
      activity and erythrocyte protective activity of ethanolic extract of Crinum
      asiaticum (L) and lycorine. The ethanolic extract of C. asiaticum (L) and
      lycorine were found to have different levels of antioxidant properties in the
      test models. Both ethanolic extract of C. asiaticum (L) (0.5-2.5 mg/ml) and
      lycorine (0.010 mg-0.050 mg/ml) increases the percentage of lipid peroxidation
      inhibition (26.25 +/- 0.23% and 19.25 +/- 0.23%) and enhances the free radical
      scavenging activity (20.92 +/- 0.22% and 20.52 +/- 0.22%), scavenging of hydrogen
      peroxide (25.67 +/- 0.17% and 23.07 +/- 0.3%) superoxide anion scavenging
      activity (27.69 +/- 0.16% and 16.09 +/- 0.7%) at concentration of 2.5 and 0.050
      mg of C. asiaticum (L) and lycorine, respectively. But compared with tocopherol
      (P < 0.05) less activity was observed by C. asiaticum (L) and lycorine. The
      ethanolic extract of C. asiaticum (L) and lycorine were normalized to reduce the
      level of glutathione and also to sustain the status of protein in erythrocytes
      during the peroxyl radical [2,2-azobis (2-amidinopropane) dihydrochloride (AAPH)]
      induced oxidative damage in ex vivo model. The present results of the
      investigations demonstrated that protective nature of the C. asiaticum (L) and
      lycorine will be considered as a significant natural antioxidant source. 

PMID- 23961123
TI  - Identifying frankincense impact by biochemical analysis and histological
      examination on rats.
AB  - Frankincense (Gum Olibanum), made from resins of Burseraceae family, grows in
      Somalia, India and Yemen. Many years ago the oldest doctors used this plant for
      treatment of many diseases. This study identifies frankincense impact by
      biochemical analysis and histological examination on rats. In this study, forty
      male Wister Albino rats weighing 70-100 g were maintained in clean cages. The
      rats were divided into 2 groups, each group contained 20 rats. Frankincense
      extract was prepared by heating distilled water (400 ml) to 80  degrees C and
      soaking 20 g of herbs for about 60 min. After cooking at room temperature the
      dose was given orally through special drinking bottles daily. The first group
      acted as control drinking water. The second group served as treated group and was
      given frankincense in the drinking water during the whole duration of the
      experiment. After 15 and 30 days of treatment, the rats were anesthetized with
      ether, and blood was collected from the livers and kidneys; some biochemical
      analyses were performed including aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), alkaline phosphatase (ALP) and non-bilirubin, urea, uric
      acid, and creatinine. Rats were killed by cervical decapitation of livers and
      kidneys. Each group was divided into 2 parts. The first part was used for the
      determination of glutathione (GSH), glucose 6 phosphate dehydrogenase (G6PDH),
      xanthine oxidase (XO), malonyldealdehyde (MDA), nitric oxide (NO), and xanthine
      oxidase (XO). The second part of livers and kidneys was kept in formalin solution
      (10%) and stained by Hematoxylin and Eosin (H & E), to be used for histological
      examination. I demonstrated in the biochemical analysis in the serum, tissue and
      histological examination, different impact between group (B) and group (A), and
      that frankincense is not absolutely safe and that precautions must be taken
      during it's us as a traditional medicine and that increase the awareness with
      safety and health hazards of many other traditional medicine is critically
      needed. 

PMID- 23961124
TI  - Effect of protease and helicase mutations on HCV NS3 activity.
AB  - Hepatitis C virus (HCV) causes serious infections in the liver which may lead to
      liver cirrhosis and hepatocellular carcinoma. Non structural 3 (NS3) protein is
      one of the most important proteins of the virus which has protease and helicase
      activities. Protease activity has a crucial role in the replication and
      persistence of the virus. Site directed mutation was carried out in the protease
      region of one NS3 and another site directed mutation in the helicase region of
      another NS3. The expression of both mutated NS3 was compared with wild NS3.
      Expression of the three different NS3 types was confirmed by in situ staining and
      western blotting using an anti-NS3 antibody and correlated with a reduced
      antiviral response after treatment with interferon-alpha. Mutation analysis
      showed that the NS3 protease activity andnot the NS3 helicase was essential for
      the inhibition of the interferon-alpha response. 

PMID- 23961125
TI  - Usage of sewage effluent in irrigation of some woody tree seedlings. Part 3:
      Swietenia mahagoni (L.) Jacq.
AB  - A pot experiment was investigated to study the effect of sewage irrigation
      treatments (primary and secondary effluents) compared with tap water on the
      growth and chemical constituents of mahogany seedlings (Swietenia mahagoni (L.)
      Jacq.) as well as soil chemical properties. The experiment was conducted at a
      greenhouse in the nursery of Timber Trees Research Department of Sabahia,
      Horticultural Research Station in Alexandria, Egypt, from June 2003 to December
      2004 for three irrigation periods (6, 12 and 18 months). The sewage effluent
      waters were taken from oxidation ponds located in New Borg EL-Arab city and used
      directly for irrigation. The primary effluent treatment was superior than other
      treatments in improving the growth parameters (plant height, stem diameter, leaf
      area, leaves number, fresh and dry weights of leaves, shoots and roots and
      shoot/root ratio) and showed the highest concentration and total uptake of N, P,
      K, Cd, Ni, Pb and Fe in plant parts, followed by secondary effluent then tap
      water. The data revealed that soil salinity in terms of electrical conductivity
      of saturated paste (EC), CaCO3%, organic matter% and soluble anions and cations
      were influenced significantly by primary or secondary effluent treatment. The
      data also showed that the use of sewage effluent for irrigation increased N, P, K
      and DTPA-extractable-heavy metals (Cd, Cu, Ni, Pb, Fe, Mn and Zn). The effects of
      sewage effluent on growth parameters and elements content in plant parts and
      treated soil were more pronounced as water treatments were used for long period.
      The results suggested that the use of sewage effluent in irrigating mahogany
      trees grown on calcareous sandy loam soil was an important agriculture practice
      for improving soil properties, increasing fuel and timber production, and is an
      economic and safe way to dispose wastewaters. 

PMID- 23961126
TI  - Quantitative analysis of nerve growth factor in the amniotic fluid during chick
      embryonic development.
AB  - Nerve growth factor (NGF) and most neurotrophic factors support the proliferation
      and survival of particular types of neurons. Besidesthe pivotal role of NGF in
      the development of neuronal cells, it also has important functions on non
      neuronal cells. The amnion surrounds the embryo, providing an aqueous environment
      for the embryo. A wide range of proteins has been identified in human amniotic
      fluid (AF). In this study, total protein concentration (TPC) and NGF level in AF
      samples from chick embryos were measured using a Bio-Rad protein assay, enzyme
      linked immunosorbent assay (ELISA) and Western blot. TPC increased from days E10
      to day E18. There was a rapid increase in AF TPC on day E15 when compared to day
      E16. No significant changes in NGF levels have been seen from day E10 to day E14.
      There was a rapid increase in NGF content on days E15 and E16, and thereafter the
      levels decreased from day E16 to day E18. Since, NGF is important in brain
      development and changes in AF NGF levels have been seen in some CNS
      malformations, changes in the TPC and NGF levels in AF during chick embryonic
      development may be correlated with cerebral cortical development. It is also
      concluded that NGF is a constant component of the AF during chick embryogenesis. 

PMID- 23961127
TI  - Subgenomic HCV RNA replication and its localization in the nucleus of the
      infected cells.
AB  - Cell culture systems have been established, where a hepatitis C virus (HCV)
      subgenomic replicon was efficiently replicated and maintained for a long period.
      It is known that HCV contains proteins which interact with host cell proteins. To
      see whether a HCV RNA replicon can interact in the same way with host cell
      proteins, HCV RNA replicon was transfected in Huh7 cells. In most infected cells,
      HCV replicon is present in the cytoplasm; however, in a minority of HCV-infected
      cells, both the cytoplasm and the nucleus or the nucleus on its own is positive
      for NS3. The presence of NS3 in the nuclei of Huh7 cells indicates that the
      protein may play a role other than in virus replication, such as in persistence
      of HCV infection. 

PMID- 23961128
TI  - DNA marker technology for wildlife conservation.
AB  - Use of molecular markers for identification of protected species offers a greater
      promise in the field of conservation biology. The information on genetic
      diversity of wildlife is necessary to ascertain the genetically deteriorated
      populations so that better management plans can be established for their
      conservation. Accurate classification of these threatened species allows
      understanding of the species biology and identification of distinct populations
      that should be managed with utmost care. Molecular markers are versatile tools
      for identification of populations with genetic crisis by comparing genetic
      diversities that in turn helps to resolve taxonomic uncertainties and to
      establish management units within species. The genetic marker analysis also
      provides sensitive and useful tools for prevention of illegal hunting and
      poaching and for more effective implementation of the laws for protection of the
      endangered species. This review summarizes various tools of DNA markers
      technology for application in molecular diversity analysis with special emphasis
      on wildlife conservation. 

PMID- 23961129
TI  - Effects of Riyadh cement industry pollutions on some physiological and
      morphological factors of Datura innoxia Mill. plant.
AB  - Cement factory emissions into air cause serious air pollution and affect the
      plant and animal life in the environment. Herein, we report the effects of cement
      industry emissions (O3, SO2 and NO2) in air, as pollutants, at Riyadh City on
      Datura innoxia Mill. plant. Morphological characters including plant height,
      leaves area and number, fresh and dry weight of shoot and root systems of D.
      innoxia showed a significant reduction from their normal control plants as a
      response to exposure to pollutant emissions. Chlorophyll and carotenoid contents
      recorded reductions in values compared to control plant, and the lowest values of
      chlorophyll A, B, total chlorophyll, carotenoids and total pigments were 0.431,
      0.169, 0.60, 0.343 and 0.943 mg/g respectively at a distance of 1-5 m from the
      cement factory in fruiting stage. These changes in values may be attributed to a
      probable deceleration of the biosynthetic process rather than degradation of
      pigments. Further D. innoxia showed a significant (P < 0.01) reduction in non
      reducing and total sugars, protein and total lipid contents compared with the
      control plant. The root system recorded the lowest values of reducing sugars
      (0.350 mg/g f. wt.), non-reducing sugars (0.116 mg/g f. wt.), total sugars (0.466
      mg/g f. wt.), protein content (0.931 mg/g f. wt.) and total lipids content (0.669
      mg/g f. wt.) in fruiting stage at a distance of 1-5 m from the cement factory.
      The peroxidase activity of shoot and root systems of the studied plant was also
      significantly higher than those of control plant. Thus a highest value of (29.616
      units/g f. wt.) peroxidase activity was recorded in vegetative stage of shoot
      system at a distance 1-5 m from the cement factory. Results of the study
      indicated that cement industry emission strongly influence the physiology and
      morphology of date palm D. innoxia which contribute date fruits, a staple food in
      the Arab world. 

PMID- 23961130
TI  - Phytophagous and predaceous mites associated with vegetable crops from Riyadh,
      Saudi Arabia.
AB  - This study was conducted to investigate phytophagous and predatory mites
      associated with vegetable plants in Riyadh, Saudi Arabia. Eight phytophagous and
      10 predacious mites were collected from 14 species of vegetable crops covering
      five major production localities. Out of these 18 mite species, 13 species are
      new to the mite fauna of Saudi Arabia. In addition, the two species, Tenuipalpus
      punicae and Agistemus exsertus, are reported for the first time on vegetable
      crops in Saudi Arabia. For each mite species found, notes on host plant
      association and occurrence period are given. An illustrated key for the
      identification of the 18 mite species reported in this study is provided and this
      can be used to improve the IPM programs by applying the local natural predatory
      mites in controlling mite pests in Saudi Arabia. 

PMID- 23961131
TI  - Short-term temporal variation in sporulation dynamics of arbuscular mycorrhizal
      (AM) fungi and physico-chemical edaphic properties of wheat rhizosphere.
AB  - In this study, we investigated the pattern of short-term temporal variation in
      the arbuscular mycorrhizal (AM) fungi and physico-chemical edaphic properties of
      some wheat growing areas of the Bundelkhand region, Central India. Rhizospheric
      soil samples were collected every month from December 2007 to May 2008 from four
      wheat growing sites around Jhansi (Bundelkhand region). AM fungal root
      colonization, sporulation and physico-chemical edaphic properties during this
      period were determined and compared to evaluate the dynamics of response of wheat
      towards the AMF along crop maturation. Maximum AMF root colonization recorded was
      54.3% indicating that AMF, particularly in low phosphorus (P) soils, can be
      important even in case of less responsive crop like wheat. In the two out of four
      sites studied, the AMF spore density increased with the increase in soil
      temperature. Absence of this type of pattern in remaining two sites indicated
      that site-specific environmental and agricultural conditions may affect the
      degree of wheat response to AMF. It also suggested that AMF communities
      inhabiting agroecosystems may exhibit considerable temporal sporulation patterns.
      The maximum AMF colonization was observed during February-March 2008, whereas
      maximum AMF sporulation was noticed during March-April 2008. Statistically
      significant negative correlation of AMF spore density with pH, organic carbon
      (OC) and available P was observed in the one of the sites studied. Overall
      assessment of the data indicated that season and location significantly affected
      the interaction of AM fungi with winter wheat necessitating the further need to
      understand the ecology of AMF populations with reference to specific host species
      under different micro-climatic conditions of Bundelkhand region. 

PMID- 23961132
TI  - Factors influencing seed germination of medicinal plant Salvia aegyptiaca L.
      (Lamiaceae).
AB  - Salvia aegyptiaca is a xerophytic perennial herb belongs to the Lamiaceae family
      commonly used for medicinal purposes. Laboratory experiments were carried out to
      assess the effects of temperature and salinity on seed germination and recovery
      responses after transferring to distilled water. Temperatures between 10 and 40 
      degrees C seem to be favourable for the germination of this species. Germination
      was inhibited by either an increase or decrease in temperature from the optimum
      (30  degrees C). The highest germination percentages were obtained at 0 mM NaCl;
      however, the increase of solution osmolalities progressively inhibited seed
      germination. The germination rate decreased with an increase in salinity for most
      of tested temperatures, but comparatively higher rates were obtained at 30 
      degrees C. Salt stress decreased both the percentage and the rate of germination.
      An interaction between salinity and temperature yielded no germination at 300 mM
      NaCl. By experimental transfer to distilled water, S. aegyptiaca seeds that were
      exposed to moderately saline conditions recovered and keep their ability to
      germinate mostly at low temperatures. At 300 mM NaCl, germination recovery
      decreased with increasing temperature and it was completely inhibited at 40 
      degrees C. 

PMID- 23961133
TI  - Administration of anti-c-kit antibody into the cerebrospinal fluid leads to
      increased cell death in the developing cerebral cortex.
AB  - It is generally believed that during development, neurons are usually produced in
      excess. Cell death occurs in the developing nervous system. The survival of the
      developing neurons depends on many factors derived from the target sites, of
      which the neuronal trophic factors are by far the best known. Stem cell factor
      (SCF) and its receptor, c-kit, is expressed in cells of nervous system during
      development and adulthood. Although the role of SCF/c-kit in the nervous system
      is so far not clear, in vitro studies indicate that SCF/c-kit is trophic to
      certain neurons derived from neural crest and cerebral cortex. In this study the
      effects of anti-c-kit antibody on cell death in the newborn chick cerebral cortex
      have been investigated. Injection of anti-c-kit antibody into the cisterna magnum
      increased the number of cell death and resulted in thinning of the cerebral
      cortex as compared to that from the control group. It is concluded that SCF/c-kit
      is essential for cortical progenitor cell survival in the cerebral cortex.
      Moreover, this method may be applied to the other factors and different CNS
      regions, allowing identification of factors involved in cell death. It
      additionally re-emphasizes the importance of further investigations into the
      potential roles of SCF/c-kit signaling in neurodegenerative diseases. 

PMID- 23961134
TI  - Effect of sowing dates and vernalization on Beta vulgaris L. cv. Univers C-leaf
      structure.
AB  - This research was conducted to study the effect of three different sowing dates
      (15th October, 15th November and 15th December) and two vernalization treatments
      (5  degrees C and -20  degrees C) on leaf structure of Beta vulgaris L. cv.
      Univers. The obtained data are summarized as follows: The maximum values of the
      most studied parameters; lower epidermis + spongy tissue thickness, midrib,
      mesophyll tissue, vascular bundle, collenchymatous tissue and number of xylem
      vessels per arm were found as a result of 15th October sowing date treatment
      compared with the two other sowing dates. Furthermore, effect of the cooling
      treatments varied according to the recorded character, sowing date and cooling
      degree. Most of the vernalization treatments at early sowing dates increased the
      mesophyll tissue, midrib, number of vascular bundles per transverse section,
      vascular bundle thickness and number of xylem arms per transverse section. The
      two studied cooling treatments at 15th October sowing date increased both
      stomatal index and average number of stomata: average number of epidermis cells
      compared with the control. Furthermore, 15th October under -20  degrees C
      treatment led to small epidermal cells and stomata formation, straight epidermal
      cell walls and closed stomata in comparison to the control. 

PMID- 23961135
TI  - Protease inhibitor from Moringa oleifera with potential for use as therapeutic
      drug and as seafood preservative.
AB  - Protease inhibitors are well known to have several applications in medicine and
      biotechnology. Several plant sources are known to return potential protease
      inhibitors. In this study plants belonging to different families of Leguminosae,
      Malvaceae, Rutaceae, Graminae and Moringaceae were screened for the protease
      inhibitor. Among them Moringa oleifera, belonging to the family Moringaceae,
      recorded high level of protease inhibitor activity after ammonium sulfate
      fractionation. M. oleifera, which grows throughout most of the tropics and having
      several industrial and medicinal uses, was selected as a source of protease
      inhibitor since so far no reports were made on isolation of the protease
      inhibitor. Among the different parts of M. oleifera tested, the crude extract
      isolated from the mature leaves and seeds showed the highest level of inhibition
      against trypsin. Among the various extraction media evaluated, the crude extract
      prepared in phosphate buffer showed maximum recovery of the protease inhibitor.
      The protease inhibitor recorded high inhibitory activity toward the serine
      proteases thrombin, elastase, chymotrypsin and the cysteine proteases cathepsin B
      and papain which have more importance in pharmaceutical industry. The protease
      inhibitor also showed complete inhibition of activities of the commercially
      available proteases of Bacillus licheniformis and Aspergillus oryzae. However,
      inhibitory activities toward subtilisin, esperase, pronase E and proteinase K
      were negligible. Further, it was found that the protease inhibitor could prevent
      proteolysis in a commercially valuable shrimp Penaeus monodon during storage
      indicating the scope for its application as a seafood preservative. This is the
      first report on isolation of a protease inhibitor from M. oleifera. 

PMID- 23961136
TI  - Hormonal regulatory role of eyestalk factors on growth of heart in mud crab,
      Scylla serrata.
AB  - The present study was attempted to know the growth regulation of eyestalk factors
      on the growth of heart in Scylla serrata using eyestalk extractions and bilateral
      eyestalk ablations. The bilateral eyestalk ablation led to the maximum growth
      indices of the heart ((H) indices) to 0.162 and 0.158 in ablated male and female,
      respectively, in comparison to 0.153 and 0.167 in the control male and female and
      0.147 and 0.157 in injected male and female, respectively. The data have shown
      that the heart of male crabs grows faster than female crabs. The study has also
      shown that bilateral eyestalk ablation resulted in a significant increase in the
      heart indices in males and has least effect on the growth of the female heart.
      The results presented strongly support a potential role of the eyestalk factors
      and molting hormone regulating the growth of the heart in S. serrata. 

PMID- 23961137
TI  - Authentication of the medicinal plant Senna angustifolia by RAPD profiling.
AB  - In this study "RAPD" molecular marker was employed for the identification of
      Senna angustifolia, Senna acutifolia, Senna tora and Senna sophera. Total 32
      decamer primers were screened in amplification with genomic DNA extracted from
      all species, of which 6 primers yielded species-specific reproducible bands. Out
      of 42 loci detected, the polymorphic, monomorphic and unique loci were 24, 2 and
      16, respectively. Based on dendrogram and similarity matrix, 4 species were
      differentiated from each other and showed more divergence. Thus, this technique
      may prove and to contribute the identification of these species of Senna having
      similar morphology sold in the local markets. 

PMID- 23961138
TI  - Purification and characterization of membrane-bound peroxidase from date palm
      leaves (Phoenix dactylifera L.).
AB  - Peroxidase from date palm (Phoenix dactylifera L.) leaves was purified to
      homogeneity and characterized biochemically. The enzyme purification included
      homogenization, extraction of pigments followed by consecutive chromatographies
      on DEAE-Sepharose and Superdex 200. The purification factor for purified date
      palm peroxidase was 17 with 5.8% yield. The purity was checked by SDS and native
      PAGE, which showed a single prominent band. The molecular weight of the enzyme
      was approximately 55 kDa as estimated by SDS-PAGE. The enzyme was characterized
      for thermal and pH stability, and kinetic parameters were determined using
      guaiacol as substrate. The optimum activity was between pH 5-6. The enzyme showed
      maximum activity at 55  degrees C and was fairly stable up to 75  degrees C, with
      42% loss of activity. Date palm leaves peroxidase showed K m values of 0.77 and
      0.045 mM for guaiacol and H2O2, respectively. These properties suggest that this
      enzyme could be a promising tool for applications in different analytical
      determinations as well as for treatment of industrial effluents at low cost. 

PMID- 23961139
TI  - Prevalence of non-strongyle gastrointestinal parasites of horses in Riyadh region
      of Saudi Arabia.
AB  - This study aimed to provide recent data on the occurrence of non-strongyle
      intestinal parasite infestation in horses in the Riyadh region of Saudi Arabia as
      a basis for developing parasite control strategies. We conducted necropsy for 45
      horses from September 2006 to November 2007 in the Riyadh region, Saudi Arabia.
      39 out of 45 horses were infected with intestinal parasites with an infestation
      rate of 86.6%. Infestations with seven nematode species and two species of
      Gasterophilus larva were found. The most prevalent parasites were Strongyloides
      westeri (64.4%) and Parascaris equorum (28.8%) followed by Habronema muscae
      (22.2%). Trichostrongylus axei and Oxyuris equi were less common at (11.1%) and
      (8.8%), respectively. Habronema megastoma and Setaria equine were found in two
      horses only (4.4%). Gasterophilus intestinalis larvae were recovered from 39
      horses (86.6%) and Gasterophilus nasalis larvae were found in 17 horses (37.7%).
      Season had a significant effect on the prevalence of P. equorum and G. nasalis,
      while age of horses had a significant effect only on the prevalence of P.
      equorum. The husbandry in Saudi Arabia appears to be conductive to parasites
      transmitted in stables or by insects rather than in pasture. 

PMID- 23961140
TI  - Protein intake and stress levels in nurses and housewives of Pakistan.
AB  - Stress has many biological effects on human daily life. In the present study,
      dietary protein intake was correlated with the investigated stress levels of
      nurses and housewives of the targeted urban population. Age group ranged from 30
      to 45 years and both the groups belonged to middle socioeconomic status. After
      calculations of environmental, psychological and physiological stresses, it was
      observed that the levels of stress in housewives were significantly higher than
      those of nurses. Recommended dietary allowances, RDA and actual protein intakes,
      API were also compared in both the groups. The found protein intake was less in
      housewives as compared to that of nurses. 

PMID- 23961141
TI  - The story of a largely unknown evolution - Germ theory hoax.
AB  - The Piltdown Man debacle provides us with the most infamous forgery in science.
      However, another equally intriguing story exists concerning a document by a
      Bostonian called George Sleeper, which purported to be a pre-Darwin-Wallace
      anticipation of evolution and an equally convincing account of the germ theory
      published before Louis Pasteur's famous studies on this subject. The story
      involves two giants in the world of evolutionary theory, Alfred Russel Wallace
      and E.B. Poulton. While Wallace was convinced that the Sleeper document was
      genuine, Poulton's detailed investigations showed that it was a fake and a hoax.
      Despite this conclusion, doubts still exist about the authenticity of the Sleeper
      document. 

PMID- 23961142
TI  - Effect of sewage water on mineral nutritive potential of six fodder species grown
      under semiarid conditions.
AB  - Investigation was performed to assess the effect of different sewage water
      treatments on the metal status of different fodder species consumed by ruminants
      under semi-arid conditions. Five samples each of six fodder species viz.,
      Trifolium alexandrinum, Cichorium intybus, Avena sativa, Medicago polymorpha,
      Brassica campestris and Medicago sativa were collected from three fields
      irrigated with canal water, mix water (canal water and sewage water) and sewage
      water, respectively. Fodder samples were analyzed to determine the Mg, Co and Zn
      concentrations in shoots. Higher values of these metals were found in fodder
      species irrigated with sewage water relatively. Mg and Zn concentrations in all
      the fodder species were found to be below the critical level among all
      treatments. Whereas, concentrations of Co in the different fodder species were
      significantly different (p < 0.05) and above the critical level. Consequently,
      ruminants feeding on these fodder species need continued mineral supplementation
      of Zn and Mg elements to prevent diseases caused by the deficiency of these
      elements, and to support optimum animal productivity. 

PMID- 23961143
TI  - Effects of different levels of wheat bran, rice bran and maize powder
      supplementation with saw dust on the production of shiitake mushroom (Lentinus
      edodes (Berk.) Singer).
AB  - The cultivation of shiitake mushroom (Lentinus edodes) is increasing rapidly in
      Bangladesh due to its nutritional and medicinal importance with excellent flavor
      and longer shelf life. With the aim of increased production, we have cultivated
      L. edodes on saw dust (SD) supplemented with different levels (10%, 15%, 20%,
      25%, 30%, 35% and 40%) of wheat bran (WB), rice bran (RB), maize powder (MP) and
      their combination (WB+RB+MP = 1:1:1) to investigate the growth, yield and quality
      of this mushroom. Most of the growth, yield and quality parameters varied
      significantly when mushrooms were cultivated with different levels of
      supplementation. The yield of mushroom was increased with the level of each
      supplementation upto a certain level, and then decreased. SD supplemented with
      25% WB produced the highest number of fruiting bodies (34.8/500 g packet),
      highest biological yield (153.3/500 g packet), and biological efficiency (76.6%)
      of L. edodes. But the yield of the best quality mushroom was observed on SD with
      40% WB supplementation; however, the qualities were not always supplementation
      dose dependent. In this study, we report that 25% WB supplementation with SD may
      be very effective for higher yield and 40% WB supplementation for better quality
      of L. edodes. 

PMID- 23961144
TI  - Insecticidal compound isolated from Syzygium lineare Wall. (Myrtaceae) against
      Spodoptera litura (Lepidoptera: Noctuidae).
AB  - A new crystal compound 2,5-diacetoxy-2-benzyl-4,4,6,6-tetramethyl-1,3
      cyclohexanedione was isolated from the leaves of Syzygium lineare. The
      insecticidal activity of the compound was assessed against fourth instar larvae
      of Spodoptera litura. Its activity was better than the positive control
      azadirachtin. The compound was responsible for growth inhibition on S. litura. It
      induced larval, pupal and adult deformities even at low concentration. The
      compound may be useful as a botanical pesticide. 

PMID- 23961146
TI  - Molecular characterization of pathogenic Fusarium species in cucurbit plants from
      Kermanshah province, Iran.
AB  - Fusarium is one of the important phytopathogenic genera of microfungi causing
      serious losses on cucurbit plants in Kermanshah province, the largest area of
      cucurbits plantation in Iran. Therefore, the objectives in this study were to
      isolate and identify disease-causing Fusarium spp. from infected cucurbit plants,
      to ascertain their pathogenicity, and to determine their phylogenetic
      relationships. A total of 100 Fusarium isolates were obtained from diseased
      cucurbit plants collected from fields in different geographic regions in
      Kermanshah province, Iran. According to morphological characters, all isolates
      were identified as Fusarium oxysporum, Fusarium proliferatum, Fusarium equiseti,
      Fusarium semitectum and Fusarium solani. All isolates of the five Fusarium spp.
      were evaluated for their pathogenicity on healthy cucumber (Cucumis sativus) and
      honeydew melon (Cucumis melo) seedlings in the glasshouse. F. oxysporum caused
      damping-off in 20-35 days on both cucurbit seedlings tested. Typical stem rot
      symptoms were observed within 15 days after inoculation with F. solani on both
      seedlings. Based on the internal transcribed spacer (ITS) regions of ribosomal
      DNA (rDNA) restriction fragment length polymorphism (RFLP) analysis, the five
      Fusarium species were divided into two major groups. In particular, isolates
      belonging to the F. solani species complex (FSSC) were separated into two RFLP
      types. Grouping among Fusarium strains derived from restriction analysis was in
      agreement with criteria used in morphological classification. Therefore, the PCR
      ITS-RFLP method provides a simple and rapid procedure for the differentiation of
      Fusarium strains at species level. This is the first report on identification and
      pathogenicity of major plant pathogenic Fusarium spp. causing root and stem rot
      on cucurbits in Iran. 

PMID- 23961145
TI  - Improvement of lipid profile and antioxidant of hypercholesterolemic albino rats
      by polysaccharides extracted from the green alga Ulva lactuca Linnaeus.
AB  - Sulfated polysaccharides from Ulva lactuca were extracted in hot water and
      precipitated by ethanol then orally gavaged to rats fed on a hypercholesterolemic
      diet for 21 days to evaluate the antihypercholesterolemic and antioxidant
      actions. Atorvastatine Ca (Lipitor) was used as a reference drug. The
      intragastric administration of U. lactuca extract to hypercholesterolemic rats
      caused significant decrease of serum total lipids, triglycerides, total
      cholesterol, LDL-cholesterol and vLDL-cholesterol levels. Whereas, HDL
      cholesterol concentration was markedly increased by 180%. Aqueous extract showed
      a significant ameliorative action on elevated atherogenic index, creatine kinase
      and lactate dehydrogenase activities of hypercholesterolemic group. Furthermore,
      serum activities of transaminases and alkaline phosphatase were also improved.
      High fat diet intake caused a highly significantly elevated serum urea,
      creatinine concentration. These effects were reversed by oral administration of
      U. lactuca extract. Sulfates polysaccharides extract of U. lactuca ameliorate
      hepatic enzymatic (catalase, glutathione peroxidase and superoxide dismutase),
      non-enzymatic (reduced glutathione & total thiol) antioxidant defenses and
      thiobarbituric acid reactive substances. In conclusion, the tested U. lactuca
      polysaccharides extract has potent hypocholesterolemic and antioxidant effects in
      experimentally-induced hypercholesterolemic animal model. 

PMID- 23961147
TI  - Effect of Lawsonia inermis on tumor expression induced by Dalton's lymphoma
      ascites in Swiss albino mice.
AB  - The purpose of this study was investigating experimentally the possible antitumor
      effect of ethanol extract of root of Lawsonia inermis against Dalton's lymphoma
      ascites (DLA) bearing mice. Mice were administered with L. inermis at a dosage of
      180 mg/kg of body weight for 15 days after 24 h of DLA inoculation. The ethanolic
      root extract of L. inermis reverted the increased number of the WBC count,
      platelets and lymphocytes and decreased the number of the RBC count, hemoglobin
      content and monocytes. The effect of root extract of L. inermis also increased
      the pathophysiological marker enzyme, lipid profile and decreased the enzymic and
      non enzymic antioxidants. A histopathological result shows the loss of liver
      hepatocytes and kidney architecture in DLA bearing mice. However, mice treatment
      with L. inermis extract improves the liver and kidney function and rearranges
      more or less normal architecture. The present work indicates that the ethanol
      extract of L. inermis exhibited significant antitumor activity. 

PMID- 23961148
TI  - Green tea (Camellia sinesis) ameliorates female Schistosoma mansoni-induced
      changes in the liver of Balb/C mice.
AB  - This study was designed to assess the effect of green tea, an aqueous extract of
      Camellia sinensis, on the oxidative stress, antioxidant defense system and liver
      pathology of Schistosoma mansoni-infected mice. Green tea at concentration of 3%
      (w/v) was given orally to treated mice as sole source of drinking water from the
      end of the 4th week to the end of 10th week post-infection; untreated mice were
      allowed to drink normal water. The data of the studied S. mansoni-infected mice
      exhibited a suppression of hepatic total antioxidant capacity, superoxide
      dismutase (SOD), catalase (CAT) activity and glutathione content. The liver lipid
      peroxidation was deleteriously elevated in S. mansoni-infected mice. The hepatic
      total protein content, AST and ALT activities were profoundly decreased in the S.
      mansoni-infected mice. Most hepatocytes were damaged and showed abnormal
      microscopic appearance with aggressive necrosis. Both total protein and glycogen
      levels have been greatly reduced as indicated by histochemical examination. The
      treatment of S. mansoni-infected mice with green tea succeeded to suppress
      oxidative stress by decreasing the lipid peroxides but failed to significantly
      enhance the antioxidant defense system and deteriorated changes owing to liver
      damage and necrosis. In consistence with biochemical data, histopathological and
      histochemical data indicated that treatment of S. mansoni-infected mice with
      green tea could ameliorate hepatocytes thus reduce cellular necrosis and
      partially restore both total protein and glycogen levels. Thus, the study
      concluded that the green tea suppresses the oxidative stress through its
      constituent with free radicals scavenging properties rather than through the
      endogenous antioxidant defense system. 

PMID- 23961149
TI  - Somatic embryogenesis, scanning electron microscopy, histology and biochemical
      analysis at different developing stages of embryogenesis in six date palm
      (Phoenix dactylifera L.) cultivars.
AB  - An efficient somatic embryogenesis system has been established in six date palm
      (Phoenix dactylifera L.) cultivars (Barhee, Zardai, Khalasah, Muzati, Shishi and
      Zart). Somatic embryogenesis (SE) was growth regulators and cultivars dependent.
      Friable embryogenic callus was induced from excised shoot tips on MS medium
      supplemented with various auxins particularly 2,4-dichlorophenoxyacetic acid (2,4
      D, 1.5 mg 1(-l)). Suspension culture increased embryogenesis potentiality. Only a
      naphthaleneacetic acid (NAA, 0.5 mg 1(-1)) produced somatic embryos in culture.
      Somatic embryos germinated and converted into plantlets in N(6)-benzyladenine
      (BAP, 0.75 mg 1(-l)) added medium following a treatment with thidiazuron (TDZ,
      1.0 mg 1(-l)) for maturation. Scanning electron microscopy showed early stages of
      somatic embryo particularly, globular types, and was in masses. Different
      developing stages of embryogenesis (heart, torpedo and cotyledonary) were
      observed under histological preparation of embryogenic callus. Biochemical
      screening at various stages of somatic embryogenesis (embryogenic callus, somatic
      embryos, matured, germinated embryos and converted plantlets) of date palm
      cultivars has been conducted and discussed in detail. The result discussed in
      this paper indicates that somatic embryos were produced in numbers and converted
      plantlets can be used as a good source of alternative propagation. Genetic
      modification to the embryo precursor cell may improve the fruit quality and yield
      further. 

PMID- 23961150
TI  - Effects of short term exposure of eggs to magnetic field before incubation on
      hatchability and post-hatch performance of meat chickens.
AB  - The effects of exposing meat-type breeder eggs to magnetic field (MF) before
      incubation on hatchability traits (percents of hatchability and hatchability
      failures of eggs), chick weight at hatch, and post-hatch performance (weight
      gain, feed intake, and feed conversion ratio (FCR)) from 1 to 39 d of age were
      investigated. Eggs from a Ross flock at 38 weeks of age were exposed to MF of 18
      Gauss (1.8 mT) at 50 Hz for 0, 15, 30, 45, 60, and 75 min (MF0, MF15, MF30, MF45,
      MF60, and MF75) before incubation. Exposing eggs to MF did not influence
      hatchability of eggs and chick weight at hatch. However, chickens of MF60 and
      MF75 treatments had lower weight gain and feed intake than those of the non
      exposed treatment at 39 d of age. MF exposure of eggs did not influence FCR of
      chickens between 1 and 21 d of age, but tended to increase FCR, albeit non
      significantly, between 22 and 39 d of age. It is concluded that exposing meat
      type breeder eggs to MF of 18 Gauss (1.8 mT) at 50 Hz for up to 75 min did not
      influence hatchability traits and chick weight at hatch. However, MF exposure of
      eggs for 60 and 75 min reduced body weight gain and feed intake of chickens over
      the 39-d experimental period. 

PMID- 23961151
TI  - Xerophilic aflatoxigenic black tea fungi and their inhibition by Elettaria
      cardamomum and Syzygium aromaticum extracts.
AB  - Black tea is consumed worldwide and is believed to play a role in cancer
      prevention. Xerophilic aflatoxigenic fungi are highly hazardous contaminants of
      tea since they are associated with tea quality impairment and human health risk.
      The present study reports isolation of such xerophilic and aflatoxigenic fungi
      associated with marketed tea. Twenty different tea samples collected from the
      local markets of Tamilnadu, India were investigated for fungal contamination. The
      results indicated contamination by 0.38% Aspergillus flavus. Other common
      contaminant fungi including Penicillium spp. (0.30%), Pacelomyces spp. (0.14%),
      and Mucor spp. (0.19%) were also isolated. Amongst the fungi isolated Aspergillus
      niger ML01 and A. flavus ML02 were found to be xerophilic aflatoxigenic
      mycoflora. Phylogenetic analysis based on 28S rRNA revealed their close ancestry.
      The chloroform and acetone extracts of spices Elettaria cardamomum and Syzygium
      aromaticum exhibited antifungal inhibitory activity on growth and toxin
      elaboration of both these xerophilic tea contaminants A. niger ML01 and A. flavus
      ML02. The results advocate the use of these spices plant or their extracts as
      novel antimicrobials which may add preservation and flavour in marketed tea. 

PMID- 23961152
TI  - Vitamin E attenuates liver injury induced by exposure to lead, mercury, cadmium
      and copper in albino mice.
AB  - Water pollution is the contamination of water resources by harmful wastes or
      toxins. Both community and private sources of drinking water are susceptible to a
      myriad of chemical contaminants. Heavy metals pollution of surface water can
      create health risks. The present study was aimed to investigate the effect of
      vitamin E supplementation on male mice exposed to a mixture of some heavy metals
      (lead, mercury, cadmium and copper) in their drinking water for seven weeks.
      Significant increases of blood alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase
      (GGT) were detected in heavy metals-treated mice. Histopathologically, the liver
      sections from heavy metals-treated mice showed severe changes including
      disarrangement of hepatic strands, rupture in hepatocytes, advanced
      hepatocellular necrosis, dilation and congestion of blood vessels with
      hemorrhage, dense lymphocytic infiltration round the central vein and dark
      stained hepatocytic nuclei indicating cell pycnosis. Administration of vitamin E
      at a dose of 50 IU/kg body weight, five times weekly improved the observed
      biochemical and histopathological changes induced by these heavy metals
      intoxication. Hence, the results of this study suggest that vitamin E protects
      against these heavy metals-induced liver injury and the attenuating effect of
      vitamin E may be due to its antioxidant activity. 

PMID- 23961153
TI  - Dietary effect of Pleurotus eryngii on biochemical function and histology in
      hypercholesterolemic rats.
AB  - This work was conducted to investigate diet supplement of king oyster mushroom
      fruiting bodies on biochemical and histological changes in hypercholesterolemic
      rats. Six-week old female Sprague-Dawley albino rats were divided into three
      groups of 10 rats each. The feeding of 5% powder of the fruiting bodies of
      Pleurotus eryngii to hypercholesterolemic rats reduced their plasma total
      cholesterol, triglyceride, low-density lipoprotein, total lipid, phospholipids,
      and LDL/HDL ratio by 24.05%, 46.33%, 62.50%, 24.63%, 19.22%, and 57.14%,
      respectively. Mushroom also significantly reduced body weight in
      hypercholesterolemic rats. However, it had no adverse effects on plasma albumin,
      total bilirubin, direct bilirubin, creatinine, blood urea nitrogen, uric acid,
      glucose, total protein, calcium, sodium, potassium, chloride, inorganic
      phosphate, magnesium, and enzyme profiles. Feeding mushroom increased total lipid
      and cholesterol excretion in feces. The plasma lipoprotein fraction, separated by
      agarose gel electrophoresis, indicated that P. eryngii significantly reduced
      plasma beta and pre-beta-lipoprotein, while increased alpha-lipoprotein. A
      histological study of hepatic cells by conventional hematoxylin-eosin and oil red
      O staining showed normal findings for mushroom-fed hypercholesterolemic rat. The
      present study suggests that 5% P. eryngii diet supplement provided health
      benefits by acting on the atherogenic lipid profile in hypercholesterolaemic
      rats. Therefore, king oyster mushroom could be recommended as a natural
      cholesterol lowering substance within the human diet. 

PMID- 23961154
TI  - The Influence of histamine H1-receptor on liver functions in immunized rabbits.
AB  - This study was designed to investigate the functional roles of histamine and
      histamine H1-receptor agonist and antagonist in the development of liver function
      impairment in immunized rabbits. The study comprised of six groups containing 18
      rabbits each. Group III-VI received histamine (100 MUg/kg, s.c.), H1R-agonist
      (HTMT, 10 MUg/kg, s.c.), H1R-antagonist (pheniramine, 10 mg/kg, i.m.), and H1R
      antagonist (pheniramine, 10 mg/kg, i.m.) plus histamine (100 MUg/kg, s.c.),
      respectively, b.i.d. for 10 days. Group I (negative control) and group II
      (positive control) received sterile distilled water intramuscularly b.i.d. for 10
      days. Groups II-VI were immunized on day 3 with intravenous injection of SRBC (1
      * 10(9) cells/ml). Blood samples were collected on pre-immunization day 0, as
      well as on days 7-, 14-, 21-, 28-, and 58-post-immunization. Biochemical
      parameters AST, ALT, alkaline phosphatase and bilirubin [total bilirubin (TB),
      direct bilirubin (DB), and indirect bilirubin (IB)] were determined. On each
      experimental day, the mean values of serum enzymes and bilirubin in group I and
      group II showed no significant changes while in group III, IV, V, and VI, these
      enzymes and bilirubin levels showed significant changes (p < 0.05), when compared
      with their experimental values within the group. The levels of serum enzymes and
      bilirubin showed significant difference (p < 0.05) in group III, IV, V, and VI on
      each experimental day, when compared with the corresponding values of each other,
      and also compared with the corresponding values of group I and II. Histamine,
      HTMT, pheniramine, and combination of histamine + pheniramine cause hepatic
      function impairment in terms of altered serum enzymes and bilirubin levels. The
      present findings suggest that HTMT causes moderate liver function impairment
      while others show mild impairment. 

PMID- 23961155
TI  - Biotechnological approaches for conservation and improvement of rare and
      endangered plants of Saudi Arabia.
AB  - Genetic variation is believed to be a prerequisite for the short-and long-term
      survival of the plant species in their natural habitat. It depends on many
      environmental factors which determine the number of alleles on various loci in
      the genome. Therefore, it is important to understand the genetic composition and
      structure of the rare and endangered plant species from their natural habitat to
      develop successful management strategies for their conservation. However, rare
      and endangered plant species have low genetic diversity due to which their
      survival rate is decreasing in the wilds. The evaluation of genetic diversity of
      such species is very important for their conservation and gene manipulation.
      However, plant species can be conserved by in situ and in vitro methods and each
      has advantages and disadvantages. DNA banking can be considered as a means of
      complimentary method for the conservation of plant species by preserving their
      genomic DNA at low temperatures. Such approach of preservation of biological
      information provides opportunity for researchers to search novel genes and its
      products. Therefore, in this review we are describing some potential
      biotechnological approaches for the conservation and further manipulation of
      these rare and endangered plant species to enhance their yield and quality
      traits. 

PMID- 23961156
TI  - Phyllosticta ophiopogonis sp. nov. from Ophiopogon japonicus (Liliaceae).
AB  - A leaf spotting disease of an ornamental variety of Ophiopogon japonicus was
      discovered at several locations in northern Thailand. In all cases a species of
      Phyllosticta was associated with the lesions. Phyllosticta ophiopogonis sp. nov.
      is distinguished from Phyllosticta species from Liliaceae in conidia size,
      mucilaginous sheath and appendage thus the species is introduced as new in this
      paper. The new species which causes unsightly lesions on this ornamental plant is
      described, illustrated and compared with other similar Phyllosticta species. 

PMID- 23961157
TI  - Control of wild oat (Avena fatua) using some phenolic compounds I - Germination
      and some growth parameters.
AB  - The percentage of germination of wild oat was significantly inhibited by
      increasing the concentrations of phenolic compounds. Ferulic acid was the most
      effective compound which completely inhibited germination at a concentration of
      3.0 mM. At the same time, wheat and barley were slightly affected with different
      concentrations of the four phenolic compounds. The percentage of germination of
      wheat significantly decreased with increasing of ferulic acid reaching a maximum
      inhibition at 3.0 mM concentration. On the other hand, the germination of wheat
      was not affected with the other three phenolic compounds. The percentage of
      germination of barley was not affected with all phenolic compounds except for
      hydroxy phenolic acetic acid which has significant effect at a concentration of
      3.0 mM. Salicylic acid significantly inhibited the growth parameters gradually in
      wild oat, wheat and barley. The shoot/root ratio was decreased in wild oat and
      barley, while the ratio increased in wheat. The growth parameters were completely
      inhibited at 3.0 mM of ferulic acid for both wild oat and wheat but slightly
      inhibited for barley. The shoot/root ratio was increased in all concentrations of
      ferulic acid except at 3.0 mM which was completely inhibited for both wild oat
      and wheat, while the ratio was increased in all treatments of ferulic acid in the
      case of barley. The growth parameters were highly significant and decreased in
      wild oat, wheat and barley with increasing the concentrations of hydroxybenzoic
      acid and hydroxyphenyl acetic acid. The shoot/root ratio was not changed in all
      concentrations except at 3.0 mM in the case of wild oat, the ratio was decreased
      at 2.0 and 3.0 mM in the case of wheat, while the ratio increased in most of
      hydroxybenzoic acid concentrations in the case of barley. The shoot/root ratio
      was increased with increasing of the hydroxyphenyl acetic acid concentrations. 

PMID- 23961158
TI  - Growth, root colonization and nutrient status of Helianthemum sessiliflorum Desf.
      inoculated with a desert truffle Terfezia boudieri Chatin.
AB  - This study aims to investigate the effects of inoculation using Terfezia boudieri
      Chatin ascospores (ectomycorrhizal fungus) on growth, root colonization and
      nutrient status of Helianthemum sessiliflorum Desf. seedlings grown in pots on
      two-soil types (gypseous and sandy loam). Mycorrhizal seedlings had significantly
      increased their height and leaf number compared to non-mycorrhizal ones.
      Regardless of mycorrhizal inoculation treatments, the plants growing on gypseous
      soil showed higher growth as compared to sandy loam one. It appears that
      inoculation with T. boudieri changed root morphology, increasing branching of
      first-order lateral roots of H. sessiliflorum seedlings. The highest root
      mycorrhizal colonization was recorded in inoculated seedlings on sandy loam soil
      (89%) when compared to gypseous one (52%). N, P and K concentrations in
      mycorrhizal seedlings were significantly improved by fungal inoculation. It can
      be concluded that inoculation of H. sessiliflorum with T. boudieri increased
      growth attributes and improved plant nutritional status. 

PMID- 23961159
TI  - Exogenous and endogenous stages of Eimeria perforans naturally infected domestic
      rabbit (Oryctolagus cuniculus) in Saudi Arabia: Light microscopic study.
AB  - Exogenous and endogenous stages of Eimeria perforans naturally infected rabbits
      in Saudi Arabia were described. The prevalence of infection was 75%. Oocysts were
      ovoid to elliptical and measured 16 * 10 MUm. The four dizoic sporocysts were
      ovoid and measured 7 * 5 MUm. Endogenous stages were restricted to the duodenum.
      Meronts, microgamonts, macrogamonts and young oocysts were recorded and
      described. 

PMID- 23961160
TI  - Viral and bacterial infections associated with camel (Camelus dromedarius) calf
      diarrhea in North Province, Saudi Arabia.
AB  - Diarrhea and deaths in new-born camel calves were noticed by veterinary
      investigators and pastoralist in Saudi Arabia to be very high. Hence, it is
      thought to be necessary to investigate this problem from the virological and
      bacteriological point of view. The role of pathogenic bacteria and viruses in six
      different towns of North Province (Al-Assafia, Arar, Domat Aljandal, Hail, Skaka
      and Khoa) in Saudi Arabia was studied. Survey was conducted in diarrheic camel
      calves aged 12 months or younger. In our study calf diarrhea was reported in 184
      out of 2308 camels examined clinically during one year, the prevalence of
      diarrhea was found to be 8.0% in calves ranging from one month to one year. In
      the present study group A rotavirus and Brucella abortus were detected in 14.7%
      and 8.98%, respectively, using ELISA technique. Escherichia coli was isolated
      from diarrheic calf camel (58.2%) 99/170 samples during dry and wet season.
      Salmonella spp. and Enterococcus spp. were detected in 12% and 8.8% of the
      specimens, respectively. In this study enterotoxogenic E. coli (ET E. coli) was
      isolated from 7% of diarrheic camel, which indicates the strong correlation
      between the camel calf diarrhea and the detection of enterotoxogenic E. coli.
      This study represented the first report for the detection of group A rotavirus
      and B. abortus antigen and antibodies in calf camels in Saudi Arabia. It is
      recommended that the disease should be controlled by vaccination in calf camels. 

PMID- 23961161
TI  - RETRACTED: Vegetation analysis of Wadi Al-Jufair, a hyper-arid region in Najd,
      Saudi Arabia.
AB  - THIS ARTICLE HAS BEEN RETRACTED: please see Elsevier Policy on Article Withdrawal
      (http://www.elsevier.com/locate/withdrawalpolicy). This article has been
      retracted at the request of the Editor-in-Chief and Author. Data processing
      errors have resulted in misleading conclusions. The scientific community in King
      Saud University has serious concerns regarding the results and the article will
      be resubmitted for publication after reprocessing of the data.

PMID- 23961162
TI  - Impact of rock materials and biofertilizations on P and K availability for maize
      (Zea Maize) under calcareous soil conditions.
AB  - The present work evaluated the synergistic effects of soil fertilization with
      rock P and K materials and co-inoculation with P and K-dissolving bacteria [PDB
      (Bacillus megaterium var. phosphaticum) and KDB (Bacillus mucilaginosus and B.
      subtilis)] on the improvement of P and K uptake, P and K availability and growth
      of maize plant grown under limited P and K soil conditions (calcareous soil). The
      experiment was establishment with eight treatments: without rock P and K
      materials or bacteria inoculation (control), rock P (RP), rock K (RK), RP + PDB,
      RK + KDB and R(P + K)+(P + K)DB. Under the same conditions of this study, co
      inoculation of PDB and KDB in conjunction with direct application of rock P and K
      materials (R(P + K)) into the soil increased P and K availability and uptake, and
      the plant growth (shoot and root growth) of maize plants grown on P and K limited
      soils. 

PMID- 23961163
TI  - Superparasitism in Cotesia glomerata does not benefit the host plant by reduction
      of herbivory caused by Pieris brassicae.
AB  - Superparasitism occurs in Cotesia glomerata L. (Hymenoptera: Braconidae), a
      gregarious endoparasitoid of Pieris spp. (Lepidoptera: Pieridae). The responses
      of Pieris brassicae L. larvae to superparasitism were examined in order to
      elucidate the ecological significance of this behaviour. Models of tritrophic
      interactions often imply that attraction of herbivore natural enemies by the
      plant constitutes a defence. Parasitoid attack on herbivores is assumed to result
      in a reduction in herbivory and or an increase in plant fitness. Coupled with the
      active involvement of the plant in producing signals, this can be seen as an
      indirect mediation of wound induced defence. The results show that
      superparasitism of P. brassicae by the parasitoid C. glomerata reduced
      survivorship but increased food consumption and weight growth in P. brassicae
      larvae. The duration of host larval development was found prolonged as the number
      of oviposition increased and superparasitized larvae (three to five time
      parasitized) grew slower than unparasitized larvae or larvae parasitized one or
      two times. 

PMID- 23961164
TI  - Dietary effects of harmine, a beta-carboline alkaloid, on development, energy
      reserves and alpha-amylase activity of Plodia interpunctella Hubner (Lepidoptera:
      Pyralidae).
AB  - The physiological and developmental effects of harmine, a beta-carboline
      alkaloid, on the insect pest Plodia interpunctella have been analyzed. When added
      at the larval diet, harmine induced a strong reduction of larvae weight,
      cannibalism between larvae, in addition to significant mortality. On the other
      hand, it caused a remarkable development disruption, manifested by both delay and
      reduction of pupation and adult emergence. Using spectrophotometric assays, we
      have shown that harmine ingestion provoked a severe reduction in protein,
      glycogen and lipid contents. Beside, when larvae fed harmine, the activity of the
      digestive enzyme alpha-amylase was strongly reduced. In conclusion, our
      experiments clearly show the susceptibility of P. interpunctella to harmine
      ingestion revealing the potent bioinsecticidal effect of harmine. 

PMID- 23961165
TI  - Cytotoxicity and antioxidant activity of 5-(2,4-dimethylbenzyl)pyrrolidin-2-one
      extracted from marine Streptomyces VITSVK5 spp.
AB  - The aim of the present study was to evaluate the cytotoxicity and antioxidant
      activity of 5-(2,4-dimethylbenzyl)pyrrolidin-2-one (DMBPO) extracted from marine
      Streptomyces VITSVK5 spp. The strain was isolated from sediment samples collected
      at the Marakkanam coast of Bay of Bengal, India. Systematic screening of isolates
      for anti-Aspergillus activity resulted in the identification of Streptomyces
      species designated as Streptomyces VITSVK5 spp. Bioactivity guided extraction and
      purification yielded a compound 5-(2,4-dimethylbenzyl)pyrrolidin-2-one (DMBPO)
      and was tested for cytotoxicity and antioxidant activity. The structure of the
      extracted compound was established by spectroscopic studies and identified as 5
      (2,4-dimethylbenzyl)pyrrolidin-2-one (DMBPO). DMBPO exhibited cytotoxic activity
      on HEP 2 and Hep G2 cell lines with the IC50 value of 2.8 MUg/ml and 8.3 MUg/ml,
      respectively, as compared to Vero cell line (22.6). DMBPO showed the hemolytic
      EC50 value of 288 MUg/ml on human erythrocytes. DMBPO treatment showed fewer
      (31.7%) aberrations, gaps and chromatid breaks as compared to untreated controls
      (27.8%) of human chromosomes. DMBPO also exhibited significant (44.13% at 5
      MUg/ml DMBPO) DPPH radical scavenging activity and total antioxidant activity
      (50.10% at 5 MUg/ml DMBPO). The results of this study showed that DMBPO is
      cytotoxic to cancer cells and possesses antioxidant property. 

PMID- 23961166
TI  - Antibacterial and phytochemical studies on Calotropis gigantia (L.) R. Br. latex
      against selected cariogenic bacteria.
AB  - In vitro antibacterial potential of the chloroform, ethyl acetate, hexane,
      methanol and aqueous extracts of Calotropis gigantia (L.) R. Br. was evaluated by
      using five cariogenic bacteria, Actinomyces viscosus, Lactobacillus acidophilus,
      Lactobacillus casei, Streptococcus mitis and Streptococcus mutans. Agar well
      diffusion method and minimum inhibitory concentration (MIC) were used for this
      purpose. The chloroform extracted fraction of latex showed inhibitory effect
      against S. mutans and L. acidophilus with MIC value of 0.032 and 0.52 mg/mL,
      respectively. Qualitative investigation on structure elucidation of bioactive
      compound using IR, NMR and GC-MS techniques revealed the presence of methyl
      nonanoate, a saturated fatty acid. 

PMID- 23961167
TI  - Acute exposure to Catha edulis depresses contractility and induces myocardial
      infarction in spontaneously contracting, isolated rabbit's heart.
AB  - Khat chewing is a recreational habit known to pose major socio-economic and
      medical problems in countries of Southern Arabia and the Horn of Africa. Among
      other adverse health effects, khat chewing has been associated with an increased
      risk of myocardial infarction (MI) in heavy consumers. This study was carried out
      to examine the direct effects of Catha edulis extract on contractility of
      spontaneously contracting, isolated rabbit heart and to investigate its mechanism
      of action. Isolated six rabbit's hearts attached to a Langendorff apparatus were
      perfused with extract at a constant flow rate and continuously bubbled with a 95%
      O2/5% CO2 gas mixture. Each heart served as its own control, as responses were
      recorded before and after administration of C. edulis extract. Varying
      concentrations of extract (50, 100 and 250 mg/ml) were loaded in the perfusate,
      their effects recorded and effluent fluid collected for assay of cardiac enzymes.
      Histological examination of the cardiac tissue was performed at the end of
      perfusion with 250 mg/ml extract. This study revealed that acute exposure to C.
      edulis extract exerted negative inotropic and chronotropic effects on isolated
      hearts. The extract also had a vasoconstrictor effect on coronary vessels,
      independent of alpha1 adrenergic receptor stimulation. Histological examination
      of hearts perfused with 250 mg/ml C. edulis extract revealed the presence of
      histological changes unique to myocardial infarction, a finding consistent with
      observed increased levels of cardiac enzymes in perfusates. Thus, we have
      demonstrated experimentally a direct cardiac depressant- and MI inducing effects
      of C. edulis extract. These results are consistent with the earlier reported
      deleterious effects of khat on cardiovascular function among khat chewers. 

PMID- 23961168
TI  - Blood chemical changes and renal histological alterations induced by gentamicin
      in rats.
AB  - Gentamicin is an effective widely used antibiotic, but the risk of nephrotoxicity
      and oxidative damage limit its long-term use. Hence, the current study aims to
      elucidate such hazardous effects. To achieve the study aim male Wistar albino
      rats (Rattus norvegicus) were exposed to gentamicin to investigate the resultant
      blood chemical changes and renal histological alterations. In comparison with
      control rats, gentamicin produced outstanding tubular, glomerular and
      interstitial alterations that included degeneration, necrosis, cytolysis and
      cortical tubular desquamation together with mesangial hypercellularity,
      endothelial cell proliferation and blood capillary congestion. Compared with
      control animals significant blood chemical changes (P < 0.05) including free
      radicals, ALT, AST, ALP, serum creatinine and serum urea were recorded in
      gentamicin-injected animals. The findings revealed that exposure to gentamicin
      can induce significant histological alterations in the kidney as well as
      remarkable blood chemical changes that might indicate marked renal failure. 

PMID- 23961169
TI  - Consequence of the antioxidant activities and tyrosinase inhibitory effects of
      various extracts from the fruiting bodies of Pleurotus ferulae.
AB  - This study was initiated to screen the antioxidant activities, tyrosinase
      inhibitory effects on the fruiting bodies of Pleurotus ferulae extracted with
      acetone, methanol and hot water. The antioxidant activities were performed on
      beta-carotene-linoleic acid, reducing power, DPPH, ferrous ions chelating
      abilities, and xanthine oxidase. In addition to this, phenolic compounds were
      also analyzed. The methanolic extract showed the strongest beta-carotene-linoleic
      acid inhibition and high reducing power as compared to other extracts. The
      scavenging effects on DPPH radicals, the acetonic and methanolic extracts were
      more effective than hot water extracts. The strongest chelating effect was
      obtained from the methanolic extract as compared to the tested synthetic
      antioxidant. Gallic acid, protocatechuic acid, caffeic acid, vanillin, ferulic
      acid, naringin, resveratrol, naringenin, hesperetin, formononetin and biochanin-A
      were detected from acetonitrile and hydrochloric acid (5:1) solvent extract.
      Xanthine oxidase and tyrosinase inhibitory activities of acetonic, methanolic,
      and hot water extracts of P. ferulae increased with increasing concentration. The
      results suggested that consumption of P. ferulae might be beneficial to the
      antioxidant, xanthine oxidase, and tyrosinase protection system of the human body
      against oxidative damage and others complications. 

PMID- 23961171
TI  - Climate change and animals in Saudi Arabia.
AB  - Global warming is occurring at an alarming rate and predictions are that air
      temperature (T a) will continue to increase during this century. Increases in T a
      as a result of unabated production of greenhouse gases in our atmosphere pose a
      threat to the distribution and abundance of wildlife populations worldwide.
      Although all the animals worldwide will likely be affected by global warming,
      diurnal animals in the deserts will be particularly threatened in the future
      because T as are already high, and animals have limited access to water. It is
      expected that Saudi Arabia will experience a 3-5  degrees C in T a over the next
      century. For predicting the consequences of global warming for animals, it is
      important to understand how individual species will respond to higher air
      temperatures. We think that populations will not have sufficient time to make
      evolutionary adjustments to higher T a, and therefore they will be forced to
      alter their distribution patterns, or make phenotypic adjustments in their
      ability to cope with high T a. This report examines how increases in T a might
      affect body temperature (T b) in the animals of arid regions. We chose three
      taxonomic groups, mammals, birds, and reptiles (Arabian oryx, Arabian spiny
      tailed lizard, vultures, and hoopoe larks) from Saudi Arabia, an area in which T
      a often reaches 45  degrees C during midday in summer. When T a exceeds T b,
      animals must resort to behavioral and physiological methods to control their T b;
      failure to do so results in death. The observations of this study show that in
      many cases T b is already close to the upper lethal limit of around 47 degrees  C
      in these species and therefore allowing their T b to increase as T a increases
      are not an option. We conclude that global warming will have a detrimental impact
      on a wide range of desert animals, but in reality we know little about the
      ability of most animals to cope with change in T a. The data presented should
      serve as base-line information on T b of animals in the Kingdom for future
      scientists in Saudi Arabia as they explore the impact of global warming on animal
      species. 

PMID- 23961173
TI  - Bismuth-inhibitory effects on bacteria and stimulation of fungal growth in vitro.
AB  - Bismuth salicylate was found to inhibit the growth of a range of bacteria and
      yeast, "Candida albicans". In general the growth of bacteria did not result in
      increase in bismuth solubilisation, in contrast, bismuth solubilisation increased
      following the growth of C. albicans. A significant increase in the biomass (dry
      weight) of Aspergillus niger and Aspergillus oryzae occurred in vitro when these
      fungi were grown in the presence of bismuth salicylate. Biomass increase occurred
      over a range of bismuth compound additions, which in the case of A. oryzae was
      associated with increase in the solubilisation of the insoluble bismuth
      compounds. 

PMID- 23961174
TI  - Rapid diagnosis of leptospirosis in patients with different clinical
      manifestations by 16S rRNA gene based nested PCR.
AB  - Leptospirosis, a zoonosis of global importance and it is underreported in India
      and more than 50,000 severe cases are reported each year. Here we present the
      evaluation of 16S rRNA based nested PCR assay for the rapid identification of
      human leptospires using serum and urine samples. The study includes 261 suspected
      cases for leptospirosis with different clinical manifestations. 16S rRNA based
      nested PCR assay was compared and evaluated against the conventional serological
      methods such as MAT and ELISA. The technique enabled amplification of a 289 bp
      product with notable percentage of positivity in all sample groups including 94.8
      in pediatric cases, 93 in pregnant women, 94.2 in renal failure, 87.8 in jaundice
      and 94.6 in common febrile cases. The sensitivity and specificity was 94.4% and
      100%, respectively. The technique proved to be prompt and effective for the
      diagnosis of leptospiral infection at the acute phase of the disease. PCR based
      approach detects leptospiral DNA from the clinical samples both at the acute and
      leptospiruria phase on comparison with its counter parts where detection is made
      possible only after 7 days or 7-30 days post-infection. In this regard PCR based
      diagnosis of leptospirosis should be made available for clinicians for the early
      diagnosis and prompt treatment of the disease. 

PMID- 23961175
TI  - Combined inoculation with Glomus intraradices and Rhizobium tropici CIAT899
      increases phosphorus use efficiency for symbiotic nitrogen fixation in common
      bean (Phaseolus vulgaris L.).
AB  - This study compared the response of common bean (Phaseolus vulgaris L.) to
      arbuscular mycorrhizal fungi (AMF) and rhizobia strain inoculation. Two common
      bean genotypes i.e. CocoT and Flamingo varying in their effectiveness for
      nitrogen fixation were inoculated with Glomus intraradices and Rhizobium tropici
      CIAT899, and grown for 50 days in soil-sand substrate in glasshouse conditions.
      Inoculation of common bean plants with the AM fungi resulted in a significant
      increase in nodulation compared to plants without inoculation. The combined
      inoculation of AM fungi and rhizobia significantly increased various plant growth
      parameters compared to simple inoculated plants. In addition, the combined
      inoculation of AM fungi and rhizobia resulted in significantly higher nitrogen
      and phosphorus accumulation in the shoots of common bean plants and improved
      phosphorus use efficiency compared with their controls, which were not dually
      inoculated. It is concluded that inoculation with rhizobia and arbuscular
      mycorrhizal fungi could improve the efficiency in phosphorus use for symbiotic
      nitrogen fixation especially under phosphorus deficiency. 

PMID- 23961172
TI  - Agaricus subrufescens: A review.
AB  - Medicinal mushrooms have currently become a hot issue due to their various
      therapeutic properties. Of these, Agaricus subrufescens, also known as the
      "almond mushroom", has long been valued by many societies (i.e., Brazil, China,
      France, and USA). Since its discovery in 1893, this mushroom has been cultivated
      throughout the world, especially in Brazil where several strains of A.
      subrufescens have been developed and used as health food and alternative
      medicine. This article presents up-to-date information on this mushroom including
      its taxonomy and health promoting benefits. Medicinal properties of A.
      subrufescens are emphasized in several studies which are reviewed here. In
      addition, safety issues concerning the use of this fungus will be discussed. 

PMID- 23961176
TI  - In vivo therapeutic potentiality of red seaweed, Asparagopsis (Bonnemaisoniales,
      Rhodophyta) in the treatment of Vibriosis in Penaeus monodon Fabricius.
AB  - The crude extract of the red seaweed, Asparagopsis sp. was evaluated for in vivo
      antibacterial activity against the shrimp vibrio pathogens. The algal extract was
      rationalized with commercial shrimp feed and orally administered for different
      duration of time followed by the artificial bacterial challenge experiment. In
      dose titration experiments, the oral administration of Asparagopsis sp. at a
      dosage of 850 mg kg(-1) of biomass was highly efficacious in the treatment of
      natural infestations of Vibriosis in Penaeus monodon. The results of the
      confirmatory dose experiment revealed that the prophylactic treatment with
      moderate dose of 850 mg kg(-1) of biomass day(-1) for four weeks followed by 14
      days of post infection therapy was highly effective in controlling Vibrio
      infection in shrimps. Moreover, results of the percent survival index and
      microbiological analysis clearly show that Asparagopsis extract incorporated
      medicated feed had broad therapeutic potential for managing shrimp Vibriosis. In
      addition, in vivo trials and results obtained in this work are based on the crude
      organic extract sourced from an unidentified Asparagopsis cryptic lineage,
      therefore further molecular analysis to identify the species will be required. 

PMID- 23961177
TI  - Amino acids content and electrophoretic profile of camel milk casein from
      different camel breeds in Saudi Arabia.
AB  - This study aimed to evaluate amino acids content and the electrophoretic profile
      of camel milk casein from different camel breeds. Milk from three different camel
      breeds (Majaheim, Wadah and Safrah) as well as cow milk were used in this study.
      Results showed that ash and moisture contents were significantly higher in camel
      milk casein of all breeds compared to that of cow milk. On the other hand, casein
      protein of cow milk was significantly higher compared to that of all camel milk
      breeds. Molecular weights of casein patterns of camel milk breeds were higher
      compared to that of cow milk. Essential (Phe, Lys and His) and non-essential
      amino acids content was significantly higher in cow milk casein compared to the
      casein of all camel milk breeds. However, there was no significant difference for
      the other essential amino acids between cow casein and the casein of Safrah breed
      and their quantities in cow and Safrah casein were significantly higher compared
      to the other two breeds. Non-essential amino acids except Arg and the essential
      amino acids (Met, Ile, Lue and Phe) were also significantly higher in cow milk
      alpha-casein compared to alpha-casein from all camel breeds. Moreover, essential
      amino acids (Val, Phe and His) and the non-essential amino acids (Gly and Ser)
      content was significantly higher in cow milk beta-casein compared to the beta
      casein of all camel milk breeds and the opposite was true for Lys, Thr, Met and
      Ile. However, Met, Ile, Phe and His were significantly higher for beta-casein of
      Majaheim compared to the other two milk breeds. The non-essential amino acids
      (Gly, Tyr, Ala and Asp) and the essential amino acids (Thr, Val and Ile) were
      significantly higher in cow milk kappa-casein compared to that for all camel milk
      breeds. There was no significant difference among all camel milk breeds in their
      kappa-casein content of most essential amino acids. Relative migration of casein
      bands of camel milk casein was not identical. The relative migration of alphas-,
      beta- and kappa-casein of camel casein was slower than those of cow casein. The
      molecular weights of alphas-, beta- and kappa-casein of camel caseins were 27.6,
      23.8 and 22.4 KDa, respectively. More studies are needed to elucidate the
      structure of camel milk. 

PMID- 23961178
TI  - Evaluation of low-intensity laser radiation on stimulating the cholesterol
      degrading activity: Part I. Microorganisms isolated from cholesterol-rich
      materials.
AB  - A survey was performed to isolate bacteria and fungi from cholesterol-rich
      sources including chicken liver, turkey giblets, salmon, lamb, egg yolk, beef
      brain and shrimps. A total of 34 bacterial and 22 fungal isolates were recovered
      from the tested sources. The highest count of isolates was recovered from the
      soil (12 isolates/g), followed by turkey giblets and egg yolk (8 isolates/g, for
      each). Out of 34 bacterial isolates, five induced the highest level in
      cholesterol degradation. The most potent bacterial isolate was recovered from
      turkey giblets and was identified as Streptomyces fradiae. In a trial to increase
      the cholesterol decomposing potentiality of S. fradiae, low intensity Nd-YAG
      laser irradiation was evaluated. The exposure of the chlorophyllin -
      photosensitized bacterium to 210 mW Nd-YAG laser for 8 min induced significant
      increase in cholesterol degrading activity reaching 73.8% as compared with 54.2%
      in the case of non-irradiated, non-photosensitized culture. Under the same
      conditions but using the reaction mixture containing cholesterol as a substrate
      and extracellular crude enzyme, the percent decomposition reached 53.7% for the
      irradiated culture as compared to 28.3% in the case of the control. Our data
      indicate the importance of the photosensitizer in enhancement of laser radiation
      to stimulate cholesterol decomposition of S. fradiae. 

PMID- 23961179
TI  - Evaluation of several holding solutions for prolonging vase-life and keeping
      quality of cut sweet pea flowers (Lathyrus odoratus L.).
AB  - Cut spikes of sweet pea (Lathyrus odoratus L.) were kept in 2% sucrose, 200 ppm 8
      hydroxyquinoline sulfate (8-HQS), pulsing treatment with 200 ppm 8-HQS in
      combination with 2% sucrose for 12 h, pulsing the spikes with 0.2 mM silver
      thiosulfate (STS) for 1 h and pulsing with 0.2 mM STS for 1 h followed by 2%
      sucrose solution. Therefore, this study aimed to see their effects on keeping
      quality and vase-life of the cut flowers. A control (deionized water) and a
      standard preservative were also included in the experiment. The results showed
      that all treatments had improved the keeping quality and vase-life of the cut
      flowers comparing to control ones. Among all these treatments, the 8-HQS combined
      with 2% sucrose showed the best water uptake, water balance, percentage of
      maximum increase in fresh weight of the cut flower stems and vase-life which was
      extended up to 17 days. Moreover, this keeping solution retarded the chlorophyll
      as well as carbohydrate degradation. However, anthocyanin concentrations were
      increased by treatments with sucrose alone or STS followed by sucrose during the
      postharvest life. It has been concluded that 200 ppm 8-HQS combined with 2%
      sucrose solution has the potential to be used as a commercial cut flower
      preservative solution to delay flower senescence, enhance post harvest quality
      and prolong the vase-life of sweet pea cut flowers. 

PMID- 23961180
TI  - Histological and histochemical alterations in the liver induced by lead chronic
      toxicity.
AB  - Adult males of the Wistar albino rats (Rattus norvegicus) were exposed to lead
      acetate trihydrate in drinking water (0.0%, 0.25%, 0.5%, 1% and 2% for 1-12
      months) to investigate histological and histochemical alterations induced by lead
      intoxication in the liver. Chronic exposure to subtoxic concentrations of lead
      produced changes in the hepatocytes, portal triads and the sinusoids. The
      alterations in the hepatocytes were mainly anisokaryosis, nuclear vesiculation,
      binucleation, cytoplasmic inclusions, cytoplasmic swelling, hydropic
      degeneration, necrosis and reduction in glycogen content. In addition, portal
      triads mild chronic inflammation, Kupffer cells hyperplasia and occasional fatty
      change were seen together with hemosiderosis. No portal fibrosis or cirrhosis was
      detected due to chronic subtoxic doses of lead exposure in the liver of any
      member of the dose groups over the entire period of the study. Chronic lead
      exposure also increased the activities of alkaline phosphatase and alpha
      glycerophosphate-dehydrogenase which might be an adaptation to the metabolic,
      structural and functional changes in the organelles of hepatic cells due to lead
      intoxication. The findings revealed that chronic exposure to lead produced
      significant histological and histochemical changes in the liver of the Wistar
      albino rats. 

PMID- 23961181
TI  - Soil seed bank in different habitats of the Eastern Desert of Egypt.
AB  - The floristic composition and species diversity of the germinable soil seed bank
      were studied in three different habitats (desert salinized land, desert wadi, and
      reclaimed land) in the Eastern Desert of Egypt. Moreover, the degree of
      similarity between the seed bank and the above-ground vegetation was determined.
      The seed bank was studied in 40 stands representing the three habitats. Ten soil
      samples (each 25 * 20 cm and 5 cm depth) were randomly taken per stand. The seed
      bank was investigated by the seedling emergence method. Some 61 species belonging
      to 21 families and 54 genera were identified in the germinable seed bank. The
      recorded species include 43 annuals and 18 perennials. Ordination of stands by
      Detrended Correspondence Analysis (DCA) indicates that the stands of the three
      habitats are markedly distinguishable and show a clear pattern of segregation on
      the ordination planes. This indicates variations in the species composition among
      habitats. The results also demonstrate significant associations between the
      floristic composition of the seed bank and edaphic factors such as CaCO3,
      electrical conductivity, organic carbon and soil texture. The reclaimed land has
      the highest values of species richness, Shannon-index of diversity and the
      density of the germinable seed bank followed by the habitats of desert wadi and
      desert salinized land. Motyka's similarity index between the seed bank and the
      above-ground vegetation is significantly higher in reclaimed land (75.1%)
      compared to desert wadi (38.4%) and desert salinized land (36.5%). 

PMID- 23961182
TI  - Possible recovery from an acute envenomation in male rats with LD50 of Echis
      coloratus crude venom: I-A seven days hematological follow-up study.
AB  - The effect of an acute LD50 dose of Echis coloratus crude venom in male albino
      rats was tested on blood parameters: white blood cells (WBCs), red blood cells
      (RBCs), platelets count, hemoglobin, hematocrit, mean cell volume (MCV), mean
      cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC), also serum
      glucose, total protein, triglycerides with alanine transaminase (ALT), aspartate
      transaminase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase
      (GGT) enzyme activities. The effect of the LD50 dose was monitored over a period
      of seven days, with time intervals of 1, 3, 6, 12, 24, 72 h. All of the tested
      parameters show fluctuations with time and with tendency to regain normal control
      level after 12 h. At 12-24 h it seems to be crucial for the process of
      physiological recovery, in spite of the irreversible damage and tissue
      distraction. The process of physiological adaptation and recovery from the lethal
      destructive venom effect seems to stabilize after one week, leaving the animal
      alive with several biochemical altered metabolisms and disturbed physiological
      profile. 

PMID- 23961183
TI  - Protective effect of Piper betle leaf extract against cadmium-induced oxidative
      stress and hepatic dysfunction in rats.
AB  - The present study was undertaken to examine the attenuative effect of Piper betle
      leaf extract (PBE) against cadmium (Cd) induced oxidative hepatic dysfunction in
      the liver of rats. Pre-oral supplementation of PBE (200 mg/kg BW) treated rats
      showed the protective efficacy against Cd induced hepatic oxidative stress. Oral
      administration of Cd (5 mg/kg BW) for four weeks to rats significantly (P > 0.05)
      elevated the level of serum hepatic markers such as serum aspartate transaminase
      (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate
      dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), bilirubin (TBRNs),
      oxidative stress markers viz., thiobarbituric acid reactive substances (TBARS),
      lipid hydroperoxides (LOOH), protein carbonyls (PC) and conjugated dienes (CD)
      and significantly (P > 0.05) reduced the enzymatic antioxidants viz., superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S
      transferase (GST), glutathione reductase (GR) and glucose-6-phosphate
      dehydrogenase (G6PD) and non-enzymatic antioxidants Viz., reduced glutathione
      (GSH), total sulfhydryls (TSH), vitamin C and vitamin E in the liver. Pre-oral
      supplementation of PBE (200 mg/kg BW) in Cd intoxicated rats, the altered
      biochemical indices and pathological changes were recovered significantly (P >
      0.05) which showed ameliorative effect of PBE against Cd induced hepatic
      oxidative stress. From the above findings, we suggested that the pre
      administration of P. betle leaf extract exhibited remarkable protective effects
      against cadmium-induced oxidative hepatic injury in rats. 

PMID- 23961184
TI  - Optimization of date syrup for enhancement of the production of citric acid using
      immobilized cells of Aspergillus niger.
AB  - Date syrup as an economical source of carbohydrates and immobilized Aspergillus
      niger J4, which was entrapped in calcium alginate pellets, were employed for
      enhancing the production of citric acid. Maximum production was achieved by pre
      treating date syrup with 1.5% tricalcium phosphate to remove heavy metals. The
      production of citric acid using a pretreated medium was 38.87% higher than an
      untreated one that consumed sugar. The appropriate presence of nitrogen,
      phosphate and magnesium appeared to be important in order for citric acid to
      accumulate. The production of citric acid and the consumed sugar was higher when
      using 0.1% ammonium nitrate as the best source of nitrogen. The production of
      citric acid increased significantly when 0.1 g/l of KH2PO4 was added to the
      medium of date syrup. The addition of magnesium sulfate at the rate of 0.20 g/l
      had a stimulating effect on the production of citric acid. Maximum production of
      citric acid was obtained when calcium chloride was absent. One of the most
      important benefits of immobilized cells is their ability and stability to produce
      citric acid under a repeated batch culture. Over four repeated batches, the
      production of citric acid production was maintained for 24 days when each cycle
      continued for 144 h. The results obtained in the repeated batch cultivation using
      date syrup confirmed that date syrup could be used as a medium for the industrial
      production of citric acid. 

PMID- 23961185
TI  - Spectrophotometric estimation of cobalt with ninhydrin.
AB  - A violet coloured complex was developed when cobalt metal reacts with ninhydrin
      at pH 8.2, using sodium acetate buffer solution. Absorbance of the complex was
      measured at 395 nm. Various factors, such as volume of the ligand used, solution
      pH, stability of the complex with time and interference of other metals, which
      effect the complex formation have been studied in detail. Present developed
      method can be used for the spectrophotometric estimation of cobalt with ninhydrin
      complex. The method is simple, selective and cheap for the determination of
      cobalt in very less time. 

PMID- 23961186
TI  - Assessment of mutagenicity induced by MMS and DES in Capsicum annuum L.
AB  - Seeds of Capsicum annuum L. var. G4 were subjected to different concentrations of
      methyl methane sulphonate (MMS) and diethyl sulphate (DES). The effects of
      different mutagenic treatments on meiosis, chiasma frequency, and pollen
      fertility have been studied in M1 generation. Various types of meiotic
      aberrations such as univalent, multivalent, stickiness, bridge, laggards,
      cytomixis etc. were observed in all the treatments. However, the MMS treatments
      proved to be more effective in inducing meiotic aberrations as compared to DES.
      Moreover, the frequency of meiotic aberrations was at its maximum at metaphase
      followed by anaphase and telophase stages. As the concentrations increase,
      reduction in chiasma frequency and pollen fertility was observed in all the
      treatments and, MMS again was found to be more effective than DES treatments. 

PMID- 23961187
TI  - Cell wall glycosidase activities and protein content variations during fruit
      development and ripening in three texture contrasted tomato cultivars.
AB  - Excessive softening is the main factor limiting fruit shelf life and storage. It
      is generally acceptable now that softening of fruit which occurs during the
      ripening is due to synergistic actions of several enzymes on cell wall
      polysaccharides. As a subject for this study, we have assayed some glycosidase
      activities using three tomato species (Lycopersicon esculentum) contrasted for
      their texture phenotypes; the cherry tomato line Cervil (Solanum lycopersicum
      var. cerasiforme), a common taste tomato line Levovil (S. lycopersicum Mill.) and
      VilB a modern line, large, firmer and with good storage capability. Four
      glycosidase activities namely alpha-galactosidase, beta-galactosidase, beta
      mannosidase and beta-glucosidase were extracted from tomato's cell wall of the
      three species. Cell wall protein from fruits pericarp was extracted and compared
      among the three cultivars at the following stages; 14 days post anthesis (14DPA)
      fruit; 21 days post anthesis (21DPA), turning (breaker), red and over ripe. When
      glycolytic activities were also compared among these cultivars at the precited
      development stages, gross variations were noticed from stage to stage and also
      from species to species in accordance with the fruit firmness status.
      Interestingly, VilB cultivar, the firmer among the other two, though possessed
      the highest total protein content, exhibited the lowest enzymatic activities.
      Taken together, these results may therefore allow us to conclude that studies of
      glycolytic activities in a single tomato cultivar cannot be generalized to all
      species. On the other hand, relating fruit development to glycosidase activities
      should logically be coupled to these enzymes from cell wall compartment. 

PMID- 23961188
TI  - In vitro regulation of sheep ovarian surface epithelium (OSE) proliferation by
      local ovarian factors.
AB  - The ovarian surface epithelium (OSE) forms a lining around the entire ovary and
      actively participates in the ovulatory cycle. To investigate how specific growth
      factors and hormones affect OSE proliferation, the present study used sheep as a
      model to examine the effects of follicular and luteal products on the
      proliferation of sheep OSE cells in culture, and to analyse the influences of
      large antral follicles and corpora lutea (CL) on the expression of gonadotrophin
      receptors (FSHR and LHR) in the OSE. In the present study, follicular fluids from
      medium and large follicles, and extracts of corpora lutea stimulated the growth
      of OSE cells. The results of the present study showed that factors in the
      follicular fluid can induce OSE proliferative activity, and this stimulation
      effect could not be attributed to steroids in the follicular fluid since
      oestrogen and progesterone treatments failed to stimulate OSE cells. The
      expression of LH and FSH receptors over large follicles (5 mm or larger) was two
      and four times higher than those over stroma and CL, respectively. In conclusion,
      OSE proliferation in cycling sheep is associated with underlying developing
      follicles and CL, mediated by, at least in part, the up-regulation of
      gonadotrophin receptors, and facilitated by the action of mitogenic glycopeptides
      and growth factors, but not steroids. 

PMID- 23961189
TI  - Antioxidants protect against increased risk of atherosclerosis induced by
      exposure to cigarette smoke: Histological and biochemical study.
AB  - BACKGROUND AND OBJECTIVES: This study aimed to assess the dose-dependent effect
      of antioxidants in protection against cardiovascular changes induced by exposure
      to cigarette smoke. DESIGN AND SETTING: This was an experimental study, conducted
      at King Fahd Medical Research Center, King Abdulaziz University. MATERIALS AND
      METHODS: This study was carried out on 57 male albino rats divided into nine
      groups. Rats of experimental groups were exposed to cigarette smoke from a total
      of 100 cigarettes per week for four weeks in a specially designed chamber. The
      antioxidants used (vitamin C, E, and B-carotene) were administrated at low (9,
      7.2, and 0.27 mg/day) and high doses (18, 14.4, and 0.54 mg/day), respectively,
      through gastric feeding tubes. The lipid profile was estimated, and the carotids
      and heart were removed, weighed, and then processed, and the carotid intima-media
      thickness was measured. Statistical analysis was performed using the Statistical
      Package for Social Sciences. RESULTS: The lipid profile was significantly
      improved in all groups treated with low or high doses of antioxidants after or
      during the exposure to cigarette smoke. Improvement was marked in the group
      treated with a high dose of antioxidants. The histological changes, as well as
      the intima-medial thickness of the carotid artery induced by exposure to
      cigarette smoke, have been improved by treatment with antioxidants (at either low
      or high doses), either after or during exposure to cigarette smoke. Improvement
      was marked in the group treated with a low dose of antioxidant. Treatment with
      antioxidants could not improve degenerated cardiac muscle fibers, while they
      could reduce the thickness of the branches of the coronary vessels. CONCLUSION:
      These results indicated that antioxidants ameliorated the cigarette smoke
      contribution to atherosclerosis, but they could not completely reverse the
      changes induced by cigarette smoke. Simultaneous intake of antioxidants could
      ameliorate the cigarette-smoke-induced changes apart from those of the heart.

PMID- 23961190
TI  - Agaricus blazei Murill as an efficient hepatoprotective and antioxidant agent
      against CCl4-induced liver injury in rats.
AB  - Agaricus blazei Murill is one of the very popular edible medicinal mushrooms. The
      present study investigated the protective effect of this biologically active
      mushroom on the tissue peroxidative damage and abnormal antioxidant levels in
      carbon tetrachloride induced hepatotoxicity in male albino rats. Male albino rats
      of Sprague-Dawley strain weighting (120-150 g) were categorized into five groups.
      The first group served as the normal control, the second and the third groups
      were treated with Agaricus blazei Mushroom extract and carbon tetrachloride dose,
      respectively. Fourth group (protective group) was first treated with Agaricus
      blazei Mushroom extract followed by carbon tetrachloride treatment and fifth
      (therapeutic group) with carbon tetrachloride first followed by Agaricus blazei
      Mushroom treatment. The wet fruiting bodies of mushroom Agaricus blazei Murill,
      crushed and suspended in distilled water was administered orally to the treated
      groups of male albino rats. The activities of various enzymes (aspartate and
      alanine transaminase, lactate dehydrogenase, glutathione reductase), levels of
      non-enzymatic antioxidants (glutathione, vitamin C, vitamin E) and level of lipid
      peroxidation (malondialdehyde) were determined in the serum of all the
      experimental animals. Decrease in all the enzymes and non-enzymatic antioxidant,
      along with an increase in the lipid peroxidative index (malondialdehyde) was
      found in all the carbon tetrachloride treated rats as compared with normal
      controls. Also increase level of non-enzymatic antioxidant along with the
      decrease level in malondialdehyde was found in all experimental animals which
      were treated with Agaricus blazei Mushroom extract as compared with normal
      controls. The findings indicate that the extract of Agaricus blazei Murill can
      protect the liver against carbon tetrachloride induced oxidative damage in rats
      and is an efficient hepatoprotective and antioxidant agent against carbon
      tetrachloride induced liver injury. 

PMID- 23961191
TI  - Integrating spatial data and shorebird nesting locations to predict the potential
      future impact of global warming on coastal habitats: A case study on Farasan
      Islands, Saudi Arabia.
AB  - One of the expected effects of the global warming is changing coastal habitats by
      accelerating the rate of sea level rise. Coastal habitats support large number of
      marine and wetland species including shorebirds (plovers, sandpipers and allies).
      In this study, we investigate how coastal habitats may be impacted by sea level
      rise in the Farasan Islands, Kingdom of Saudi Arabia. We use Kentish plover
      Charadrius alexandrinus - a common coastal breeding shorebird - as an ecological
      model species to predict the influence of sea level rise. We found that any rise
      of sea level is likely to inundate 11% of Kentish plover nests. In addition, 5%
      of the coastal areas of Farasan Islands, which support 26% of Kentish plover
      nests, will be flooded, if sea level rises by one metre. Our results are
      constrained by the availability of data on both elevation and bird populations.
      Therefore, we recommend follow-up studies to model the impacts of sea level rise
      using different elevation scenarios, and the establishment of a monitoring
      programme for breeding shorebirds and seabirds in Farasan Islands to assess the
      impact of climate change on their populations. 

PMID- 23961192
TI  - Bacillus subtillis RTSBA6 6.00, a new strain isolated from gut of Helicoverpa
      armigera (Lepidoptera: Noctuidae) produces chymotrypsin-like proteases.
AB  - Exploring bacterial communities with proteolytic activity from the gut of the
      Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae) insect pests was the
      purpose of this study. As initial efforts to achieve this goal here we report the
      isolation of new Bacillus subtillis RTSBA6 6.00 strain from the gut of H.
      armigera and demonstrated as proteases producer. Zymographic analysis revealed 12
      proteolytic bands with apparent molecular weights ranging from 20 to 185 kDa.
      Although some activity was detected at acidic pH, the major activity was observed
      at slight alkaline pH (7.8). The optimum temperature was found to be 35  degrees
      C with complete loss of activity at 70  degrees C. All proteases were completely
      inactivated by PMSF (phenylmethylsulfonyl fluoride) and TPCK (N-tosyl-l
      phenylalanine chloromethyl ketone), suggesting that proteases secreted by B.
      subtillis RTSBA6 6.00 belong to serine proteases class with chymotrypsin-like
      activity. The occurrence of protease producing bacterial community in the gut of
      the H. armigera advocates its probable assistance to insect in proteinaceous food
      digestion and adaptation to protease inhibitors of host plants. 

PMID- 23961193
TI  - Foliar spray of brassinosteroid enhances yield and quality of Solanum
      lycopersicum under cadmium stress.
AB  - The presence of cadmium in the soil above a particular level is proposed to check
      not only plant growth but also productivity and fruit quality. Therefore, in the
      present study investigations are directed to evaluate the effect of four levels
      of cadmium (3, 6, 9, 12 mg kg(-1)) in interaction with two analogs of
      brassinosteroids on the growth, fruit yield and quality of tomato. Under
      greenhouse conditions plants were analyzed for antioxidant system activity and
      photosynthetic assimilation efficiency. Cd stressed plants exhibited poor growth
      and biological yield. The metal also had a negative impact on the antioxidant
      system of the resulting fruits. However, the follow up application of BRs (10(-8)
      M) neutralized the damaging effects of the metal on the plants. 

PMID- 23961194
TI  - Comparisons of direct extraction methods of microbial DNA from different paddy
      soils.
AB  - Molecular analyses for the study of soil microbial communities often depend on
      the direct extraction of DNA from soils. The present work compares the
      effectiveness of three different methods of extracting microbial DNA from seven
      different paddy soils. Comparison among different DNA extraction methods against
      different paddy soil samples revealed a marked variation in DNA yields from 3.18
      20.17 MUg DNA/g of dry soil. However, irrespective of the soil samples and
      extraction methods the DNA fragment size was >10 kb. Among the methods evaluated,
      method-C (chemical-enzymatic-mechanical) had better cell lysis efficiency and DNA
      yield. After purification of crude DNA by Purification Kit, A260/A230 and
      A260/A280 ratios of the DNA obtained by method-C reached up to 2.27 and 1.89,
      respectively, sustaining the efficacy of this technique in removing humic acid,
      protein and other contaminants. Results of the comprehensive evaluation of DNA
      extraction methods suggest that method-C is superior to other two methods
      (chemical-enzymatic and chemical-mechanical), and was the best choice for
      extraction of total DNA from soil samples. Since soil type and microbial
      community characteristics influence DNA recovery, this study provides guidance
      for choosing appropriate extraction and purification methods according to
      experimental goals. 

PMID- 23961195
TI  - Characterization, feasibility and optimization of Agaricus subrufescens growth
      based on chemical elements on casing layer.
AB  - The aim of this study was to analyze yields, biological efficiency, earliness
      (expressed as days to first harvest), and precociousness and establish models for
      the mushroom growing according to these parameters. The experiment followed a
      double factorial design with four sources of calcium (calcitic limestone,
      calcitic limestone + gypsum, dolomitic limestone and dolomitic limestone +
      gypsum) and 2 application times (25 days before casing and at the moment of
      casing), with 4 replicates for each treatment. Different calcium sources
      influenced differently Agaricus subrufescens production, especially as regards
      earliness, which showed significantly higher values when dolomitic limestone with
      gypsum was applied. Yield and biological efficiency were negatively correlated
      with H + AL, organic matter and Mg amount. Furthermore, earliness was positively
      correlated with H + Al, organic matter, and the amount of Mg and Fe. Finally,
      negative correlations were observed between precociousness and the amount of Ca,
      SB (sum of base), CEC (cation exchange capacity) and V% (percentage of base
      saturation). The models presented in this work are extremely important for
      predicting the agronomic performance of Agaricus subrufescens on the basis of
      chemical analysis provided by the casing soil. 

PMID- 23961196
TI  - Antioxidant activity of polyphenolic extracts of Ichnocarpus frutescens.
AB  - In the present study antioxidant activities by (1,1-diphenyl-2-picrylhydrazyl
      radical (DPPH), hydrogen peroxide, hydroxyl radical inhibition, hemolysis by
      hydrogen peroxide assay, reducing power and total antioxidant activities of
      polyphenolic extract of Ichnocarpus frutescens leaves were investigated. The
      flavonoids and total polyphenolic contents of the extract were also determined
      using standard methods. Phytochemical analyses revealed the presence of
      flavonoids, polyphenols, anthocyanins and simple phenolic acids. The results of
      antioxidant activities of polyphenol extract obtained by different in vitro
      methods were varied depending on the method used. Nevertheless, polyphenol
      extract showed significant inhibitory activities in all in vitro reactive oxygen
      species scavenging, might be attributed due to the high level of polyphenolic
      compound. Also, these various antioxidant activities were compared to alpha
      tocopherol and l-ascorbic acid as reference antioxidant compounds. These findings
      provide evidence that the polyphenolic extract of I. frutescens is a natural
      source of antioxidant against oxidative damage. 

PMID- 23961197
TI  - Vegetation analysis of Wadi Al-Jufair, a hyper-arid region in Najd, Saudi Arabia.
AB  - Wadi Al-Jufair, a tributary of Wadi Nisah, is one of the important wadis of Najd
      region (Saudi Arabia) sheltering a rich diversity of higher plants. The study
      area is extended into approximately 15 km(2) encompassing the commonest
      geomorphological features encountered in desert wadis. The wadi supports several
      rare plants, including Maerua crassifolia Forssk., a regionally endangered tree,
      and Acacia oerfota (Forssk.) Schweinf., a rare shrub with restricted
      distribution. The present study aims to analyze the vegetation of wadi Al-Jufair
      and propose its designation as an important plant reserve. The vegetation type is
      fundamentally of chamaephytic nature with some phanerophytes, and distinguished
      into associations where the dominant perennial species give the permanent
      character of plant cover in each habitat. Four vegetation groups were identified
      with the application of TWINSPAN, DCA and CCA programs and named after the
      characteristic species as follows: Lycium shawii; A. oerfota; Acacia raddiana
      Rhazya stricta and Artemisia monosperma. These plant associations demonstrate
      significant variation in soil texture, moisture, organic matter, pH, EC, and
      minerals of Wadi Al-Jufair.

PMID- 23961198
TI  - Composition and diversity of weed communities in Al-Jouf province, northern Saudi
      Arabia.
AB  - The aim of this study was to identify the main weed communities in Al-Jouf
      province in northern Saudi Arabia. Moreover, the composition and diversity of
      these communities were studied in relation to soil variables and crop type. Some
      54 stands representing olive orchards, date palm orchards, wheat crop and
      watermelon crop were studied, using ten quadrats (1 * 1 m) per stand. A total of
      71 species belonging to 22 families and 61 genera were observed. The
      classification of vegetation using the Two Way Indicator Species Analysis
      (TWINSPAN) resulted in the recognition of four vegetation groups representing
      wheat crop, orchards in winter season, orchards in summer season and watermelon
      crop. These results suggested the importance of both crop and season for the
      formation of weed community. Detrended Correspondence Analysis (DCA) showed that
      these groups are clearly distinguished by the first two DCA axes. The species
      richness was higher in both olive and date palm orchards than in wheat and
      watermelon crops. This pattern of species richness could be related to farm
      management practices and habitat micro-heterogeneity. Soil electrical
      conductivity, organic carbon and soil texture showed significant correlations
      with species richness and the cover values of some dominant species, suggesting
      the significant role of soil characteristics in weed community structure and
      diversity. 

PMID- 23961199
TI  - Contrasting soil microbial responses to fertilization and tillage systems in
      canola rhizosphere.
AB  - Information regarding the simultaneous evaluation of tillage and fertilization on
      the soil biological traits in canola production is not available. Therefore,
      field experiments were conducted in 2007-2010 in a split plot based on randomized
      complete block design with three replications. Main plots consisted of
      conventional tillage (CT); minimum tillage (MT) and no tillage (NT). Six
      strategies of fertilization including (N1): farmyard manure (cattle manure);
      (N2): compost; (N3): chemical fertilizers; (N4): farmyard manure + compost; (N5):
      farmyard manure + compost + chemical fertilizers and (N6): control, were arranged
      in sub plots. Results showed that the addition of organic manure increased the
      soil microbial biomass. No tillage system increased microbial biomass compared to
      other tillage systems. The activities of all enzymes were generally higher in the
      N4 treatment. The activity of phosphatase and urease tended to be higher in the
      no tillage treatment compared to the CT and MT treatments. 

PMID- 23961200
TI  - Biochemical and histological impact of Vernonia amygdalina supplemented diet in
      obese rats.
AB  - This study was carried out to evaluate the anti-obesity effect of Vernonia
      amygdalina Del. (VA) supplemented diet. VA leaf powder was fed at 5% and 15% to
      diet-induced obese rats for 4 weeks and its effect compared with orlistat (5.14
      mg/kg p.o.), an anti-obesity drug. Food intake, body and organ weights, total
      body fat, some lipid components and amino transaminase activities in serum,
      hepatocytes and brain; as well as serum glucose, were measured during or at end
      of the study. Result showed respective decrease of 12.78% and 38.51% in body
      weight gain, of VA fed rats against 17.45% of orlistat at end of study (P <
      0.05); but with no effect on food intake. Total body fat was lowered by 28.04%
      and 30.02% vs. obese control rats (CDC) (P < 0.05). Furthermore, serum
      triacylglycerol (TG), serum and brain total cholesterol (TCHOL), were down
      regulated at 15% VA supplementation (P < 0.05). Serum glucose which increased in
      obese rats by 46.26% (P < 0.05) vs. NC, indicating intolerance, was restored by
      VA (38.75% and 34.65%) and orlistat (31.80%) vs. CDC (P < 0.05). VA diet also
      exerted hepato-protection, via lowering serum alanine amino transaminase (ALT)
      (41.35% and 27.13%) and aspartate amino transaminase (AST) (17.09% and 43.21%)
      activities (P < 0.05). Orlistat had no effect on these enzymes. Histology of
      adipose tissue corroborated the changes on total body fat. We concluded that,
      diet supplemented with VA can attenuate dietary obesity as well as ameliorates
      the potential risks of hepato-toxicity and glucose intolerance associated with
      obesity. 

PMID- 23961201
TI  - Retraction notice "Vegetation analysis of Wadi Al-Jufair, a hyper arid region in
      Najd, Saudi Arabia" [Saudi Journal of Biological Sciences 19 (1) (2012) 43-54].
AB  - [This corrects the article DOI: 10.1016/j.sjbs.2011.09.004.][This corrects the
      article DOI: 10.1016/j.sjbs.2012.04.003.]. 

PMID- 23961202
TI  - RNA interference: A futuristic tool and its therapeutic applications.
AB  - RNA interference is a post transcriptional gene silencing mechanism that is
      triggered by double-stranded RNA (dsRNA). Various attributes of the 3' end
      structure, including overhang length and sequence composition, plays a primary
      role in determining the position of the Dicer cleavage in both dsRNA and
      unimolecular, short hairpin RNA (shRNA). The specificity and robustness of RNAi
      have triggered an immense interest in using RNAi as a tool in various settings.
      RNAi is a mechanism for controlling normal gene expression which has recently
      began to be employed as a potential therapeutic agent for a wide range of
      disorders, including cancer, infectious diseases and metabolic disorders.
      Clinical trials with RNAi have now begin, but major obstacles, such as off-target
      effects, toxicity and unsafe delivery methods, have to be overcome before RNAi
      can be considered as a conventional drug. It is also used as a tool to improve
      crops by providing resistance against parasites and modified versions of siRNA
      that are directed against disease causing genes are being developed, some of
      which are already tested in clinical trials. In this paper, we first reviewed the
      RNAi mechanism and then focussed on some of its applications in biomedical
      research such as treatment for HIV, viral hepatitis and several other diseases. 

PMID- 23961204
TI  - Biodegradation of microcystin-RR by Bacillus flexus isolated from a Saudi
      freshwater lake.
AB  - A bacterium capable of degrading microcystin-RR (MC-RR) was isolated from a Saudi
      eutrophic lake which was previously reported to have microcystin-producing
      cyanobacteria. Based on the analysis of the 16S rRNA gene sequence, the isolated
      strain SSZ01, most likely belong to the genus Bacillus with a highest sequence
      similarity (99%) with Bacillus flexus strain EMGA5. It was found that B. flexus
      strain SSZ01, possesses an mlrA gene encoding the most important enzyme for MC
      degradation. This strain was capable of degrading MC-RR, at a concentration of 10
      mg l(-1), in batch experiments under environmentally relevant conditions. The
      degradation of MC-RR was completely removed within 4 d. The degradation of MC-RR
      by this strain occurred in a rich medium nutrient broth (NB), indicating that
      this could likely occur along with other organic compounds found in the
      environment. Therefore, the coexistence of such bacteria with MCs in the same
      environment can contribute to the self-purification of the ecosystem from such
      potent toxins. This is the first study to report that B. flexus can degrade MCs. 

PMID- 23961205
TI  - Effects of raw and diluted municipal sewage effluent with micronutrient foliar
      sprays on the growth and nutrient concentration of foxtail millet in southeast
      Iran.
AB  - In this study, the effect of irrigation with raw or diluted municipal sewage
      effluent accompanied by foliar micronutrient fertilizer sprays was examined on
      the growth, dry matter accumulation, grain yield, and mineral nutrients in
      foxtail millet plants. The experimental design was a split plot with three
      irrigation sources: raw sewage, 50% diluted sewage, and well water comprising the
      main treatments, and four combinations of Mn and Zn foliar sprays as sub
      treatments that were applied with four replications. The experiment was conducted
      in 2009 at the Zabol University research farm in Zabol, south Iran. The applied
      municipal sewage effluent contained higher levels of micronutrients and
      macronutrients and exhibited greater degrees of electrical conductivity compared
      to well water. Because of the small scale of industrial activities in Zabol, the
      amount of heavy metals in the sewage was negligible (below the limits set for
      irrigation water in agricultural lands); these contaminants would not be severely
      detrimental to crop growth. The experimental results indicated that irrigation of
      plants with raw or diluted sewage stimulates the measured growth and productivity
      parameters of foxtail millet plants. The concentrations of micronutrients and
      macronutrients were also positively affected. These stimulations were attributed
      to the presence of high levels of such essential nutrients as N, P, and organic
      matter in wastewater. Supplied in sewage water alone, Mn and Zn were not able to
      raise the productivity of millet to the level obtained using fertilizers at the
      recommended values; this by itself indicated that additional nutrients from
      fertilizers are required to obtain higher levels of millet productivity with
      sewage farming. Despite the differences in nutrient concentrations among the
      different irrigation water sources, the micronutrient foliar sprays did not
      affect the concentrations of micronutrients and macronutrients in foxtail millet
      plants. These results suggested that municipal sewage effluent could be utilized
      efficiently as an important source of water, and that the nutrients used in
      growing foxtail millet with sewage water irrigation did not have any significant
      harmful effect on crop productivity. In contrast, the nutrients proved beneficial
      to soil fertility and millet productivity and quality. 

PMID- 23961203
TI  - Fungal pollution of indoor environments and its management.
AB  - Indoor environments play important roles in human health. The health hazards
      posed by polluted indoor environments include allergy, infections and toxicity.
      Life style changes have resulted in a shift from open air environments to air
      tight, energy efficient, environments, in which people spend a substantial
      portion of their time. Most indoor air pollution comes from the hazardous non
      biological agents and biological agents. Fungi are ubiquitous in distribution and
      are a serious threat to public health in indoor environments. In this
      communication, we have reviewed the current status on biotic indoor air
      pollution, role of fungi as biological contaminants and their impact on human
      health. 

PMID- 23961206
TI  - Alleviation of fungicide-induced phytotoxicity in greengram [Vigna radiata (L.)
      Wilczek] using fungicide-tolerant and plant growth promoting Pseudomonas strain.
AB  - This study was designed to explore beneficial plant-associated rhizobacteria
      exhibiting substantial tolerance against fungicide tebuconazole vis-a-vis
      synthesizing plant growth regulators under fungicide stressed soils and to
      evaluate further these multifaceted rhizobacteria for protection and growth
      promotion of greengram [Vigna radiata (L.) Wilczek] plants against phytotoxicity
      of tebuconazole. Tebuconazole-tolerant and plant growth promoting bacterial
      strain PS1 was isolated from mustard (Brassica compestris) rhizosphere and
      identified as Pseudomonas aeruginosa following 16S rRNA gene sequencing. The P.
      aeruginosa strain PS1 solubilized phosphate significantly and produced indole
      acetic acid, siderophores, exo-polysaccharides, hydrogen cyanide and ammonia even
      under tebuconazole stress. Generally, tebuconazole at the recommended, two and
      three times the recommended field rate adversely affected the growth, symbiosis,
      grain yield and nutrient uptake in greengram in a concentration dependent manner.
      In contrast, the P. aeruginosa strain PS1 along with tebuconazole significantly,
      increased the growth parameters of the greengram plants. The inoculant strain PS1
      increased appreciably root nitrogen, shoot nitrogen, root phosphorus, shoot
      phosphorus, and seed yield of greengram plants at all tested concentrations of
      tebuconazole when compared to the uninoculated plants treated with tebuconazole.
      The results suggested that the P. aeruginosa strain PS1, exhibiting novel plant
      growth regulating physiological features, can be applied as an eco-friendly and
      plant growth catalyzing bio-inoculant to ameliorate the performance of greengram
      in fungicide stressed soils. 

PMID- 23961207
TI  - Effect of gold nanoparticles on glutathione and malondialdehyde levels in liver,
      lung and heart of rats.
AB  - We studied the effect of gold nanoparticles (NPs) on oxidative stress markers
      including reduced glutathione (GSH) and malondialdehyde (MDA) in different organs
      of rats. Adult male Wistar-Kyoto rats were randomly divided into 3 groups of 5
      animals each. One group served as control and received vehicle only. The
      remaining two groups were treated with 50 MUl of 10 nm sized gold NPs, daily for
      3 and 7 days, respectively. The rats were sacrificed 24 h after the last
      injection of NPs. Administration of gold NPs did not cause any significant change
      in GSH levels in liver, lung and heart on day 3 or day 7. There was no
      significant effect of gold NPs on MDA levels in lung and heart whereas
      significant increases in MDA levels were found in the liver of rats treated with
      gold nanoparticles on both 3 and 7 days post-dosing (ANOVA F = 7.113, P = 0.010).
      In conclusion, the findings of this preliminary study suggest that gold NPs of 10
      nm diameter produce significant lipid peroxidation in rat liver however lungs and
      heart do not show any oxidative stress. Further studies are warranted to examine
      the effects of a broader dose range of gold NPs on the levels of free radical
      indices in different organs of rats. 

PMID- 23961208
TI  - Bionanotechnology approach for FAD-dependent enzymes with nanomaterials sensor.
AB  - We have reported the modification of biomolecule with nanomaterials. In this
      paper, the electrochemical response of different FAD-dependent enzymes at carbon
      nanomaterials modified electrode. The modified electrode also exhibits a
      promising enhanced electrocatalytic activity toward the oxidation of substrate.
      Different methods were used for fabrication of modified electrode. The presence
      of nanomaterials enhances the enzyme loading and stability. Cyclic voltammograms
      (CVs) were used for the determination of substrate and the apparent coefficient
      values for these compounds at different electrodes. Finally, we have studied the
      surface morphology of the modified electrode using scanning electron microscopy
      (SEM), which revealed that enzyme is coated on nanomaterials. 

PMID- 23961209
TI  - High temperature combined with drought affect rainfed spring wheat and barley in
      South-Eastern Russia: I. Phenology and growth.
AB  - Heat stress, when combined with drought, is one of the major limitations to food
      production worldwide, especially in areas that use rainfed agriculture. As the
      world population continues to grow, and water resources for the crop production
      decline and temperature increases, so the development of heat- and drought
      tolerant cultivars is an issue of global concern. In this context, four barley
      and two wheat genotypes were evaluated in south-eastern Russia to identify heat-
      and drought-tolerant genotypes for future breeding programmes by identifying
      suitable sowing times for specific genotypes. High temperature stress, when
      combined with drought during late sowing, decreased the days to visible awns,
      days to heading and days to ripe harvest, finally negatively affecting the growth
      and development of plants and resulting in a lower plant population m(-2),
      tillers plant(-1), plant height and dry matter production m(-2). On the other
      hand, low temperature in combination with early sowing increased the number of
      days to germination, reduced seedling stand establishment and tillering capacity,
      finally affecting the growth and development of the crops. Compared to overall
      performance and optimum sowing date, barley genotypes 'Zernograd.770' and
      'Nutans', and wheat genotype 'Line4' performed best in both late (high
      temperature with drought) and early (low temperature) stress conditions. 

PMID- 23961210
TI  - Starvation induced cholesterogenesis in hepatic and extra hepatic tissues of
      climbing Perch, Anabas testudineus (Bloch).
AB  - Cholesterol is a structural lipid, which may be differentially utilized or
      synthesized in response to stress or during insulin deficient states such as
      starvation. In the present investigation we estimated the levels of cholesterol
      in Anabas testudineus, which was subjected to brief (15 days) and prolonged
      fasting (60 days). Tissues such as liver, kidney, brain, accessory respiratory
      organ, pectoral and lateral line muscle were selected for the study. Cholesterol
      content was estimated by the Crawford method (1958). Both the starvation regimes
      showed a significant increase in cholesterol levels in almost all the tissues,
      but for liver, which strangely showed an insignificant decline during the short
      term starvation. This overall upsurge in cholesterol levels observed in all extra
      hepatic tissues may be attributed to the synthesis of stress hormones such as
      glucocorticoids, which may promote gluconeogenesis and adrenocorticoids, which
      may help the animal to combat the stressful condition of starvation. Anabas
      adapted well to starvation stress and survived all throughout the experimental
      period. 

PMID- 23961211
TI  - Neuronal activation and plasticity in Schistosoma mansoni infected mice.
AB  - Schistosomiasis leads to structural and functional changes which may result from
      unbalanced release of some inflammatory mediators. The aim of the study was to
      investigate the effect of intestinal parasitic infection on nitric oxide release
      and to evaluate the neural plasticity that leads to motility disturbance.
      Experiments were performed in Swiss mice 8- and 12-weeks following infection with
      Schistosoma mansoni compared to untreated controls. Jejunal motility was assessed
      using a Trendelenburg preparation to study aboral directed peristaltic pressure
      waves. Histological examination was used to determine the pathological
      characteristics of inflammation. Parasitic infection produces diffuse
      inflammatory infiltrate in both 8- and 12-weeks infected animals. Inflammation
      had significant effect on peristaltic pressure waves amplitude and intervals at 8
      weeks compared to control; whereas, in 12-weeks post infection there was a
      significant decrease in peristaltic pressure waves amplitude and interval
      compared to 8- weeks and control. Nitric oxide synthase inhibitor (L-NAME 100
      MUM) induced a significant increase in amplitude and decrease in intervals in
      control, 8- and 12- weeks infected animals. In conclusion, parasitic infection
      leads to disturbance in the release of the inflammatory mediators. This study
      indicated the role of nitric oxide in developing granulomatous inflammation and
      participating in motility disturbance. 

PMID- 23961212
TI  - Mosquito larvicidal activity of Aloe vera (Family: Liliaceae) leaf extract and
      Bacillus sphaericus, against Chikungunya vector, Aedes aegypti.
AB  - The bio-efficacy of Aloe vera leaf extract and bacterial insecticide, Bacillus
      sphaericus larvicidal activity was assessed against the first to fourth instars
      larvae of Aedes aegypti, under the laboratory conditions. The plant material was
      shade dried at room temperature and powdered coarsely. A. vera and B. sphaericus
      show varied degrees of larvicidal activity against various instars larvae of A.
      aegypti. The LC50 of A. vera against the first to fourth instars larvae were
      162.74, 201.43, 253.30 and 300.05 ppm and the LC90 442.98, 518.86, 563.18 and
      612.96 ppm, respectively. B. sphaericus against the first to fourth instars
      larvae the LC50 values were 68.21, 79.13, 93.48, and 107.05 ppm and the LC90
      values 149.15, 164.67, 183.84, and 201.09 ppm, respectively. However, the
      combined treatment of A. vera + B. sphaericus (1:2) material shows highest
      larvicidal activity of the LC50 values 54.80, 63.11, 74.66 and 95.10 ppm; The
      LC90 values of 145.29, 160.14, 179.74 and 209.98 ppm, against A. aegypti in all
      the tested concentrations than the individuals and clearly established that there
      is a substantial amount of synergist act. The present investigation clearly
      exhibits that both A. vera and B. sphaericus materials could serve as a potential
      larvicidal agent. Since, A. aegypti is a container breeder vector mosquito this
      user and eco-friendly and low-cost vector control strategy could be a viable
      solution to the existing dengue disease burden. Therefore, this study provides
      first report on the mosquito larvicidal activity the combined effect of A. vera
      leaf extract and B. sphaericus against as target species of A. aegypti. 

PMID- 23961213
TI  - Soil cadmium enrichment: Allocation and plant physiological manifestations.
AB  - Cadmium (Cd) in soil is enriched through several leaky management agricultural
      practices and natural resources. Cd enriched soil is inevitable cause of
      nutritional stress besides Cd induced toxicity symptoms and physiological
      malfunctions. Redox signals shift toward oxidative stress which accelerates
      cellular damage and elicits defense mechanism at the cost of growth. Plants get
      enriched with this toxic, abundant and undesirable element through 'mineral
      uptake system' non-specifically. Different components and pathways have been
      marked cooperating in cellular sequestration and systemic localization of Cd,
      escaped from avoidance and efflux. Cd induced metabolic alteration led to
      electron leakage as ROS, reduced photosynthesis and carbon fixation. Compromised
      primary metabolism negatively feedbacks the plant growth, result into loss of
      potential crop yield. 

PMID- 23961214
TI  - Biological nutrient removal with limited organic matter using a novel anaerobic
      anoxic/oxic multi-phased activated sludge process.
AB  - An anaerobic-anoxic/oxic (A2/O) multi-phased biological process called "phased
      isolation tank step feed technology (PITSF)" was developed to force the
      oscillation of organic and nutrient concentrations in process reactors. PITSF can
      be operated safely with a limited carbon source in terms of low carbon
      requirements and aeration costs whereas NAR was achieved over 95% in the last
      aerobic zone through a combination of short HRT and low DO levels. PCR assay was
      used for XAB quantification to correlate XAB numbers with nutrient removal. PCR
      assays showed, high NAR was achieved at XAB population 5.2 * 10(8) cells/g MLVSS
      in response to complete and partial nitrification process. It was exhibited that
      low DO with short HRT promoted XAB growth. Simultaneous nitrification and
      denitrification (SND) via nitrate were observed obviously, SND rate was between
      69-72%, at a low DO level of 0.5 mg/l in the first aerobic tank during main
      phases and the removal efficiency of TN, [Formula: see text], COD, TP was 84.7
      .97, 88.3 and 96% respectively. The removal efficiencies of TN, [Formula: see
      text], and TP at low C/N ratio and DO level were 84.2, 98.5 and 96.9%
      respectively which were approximately equal to the complete nitrification
      denitrification with the addition of external carbon sources at a normal DO level
      of (1.5-2.5 mg/l). 

PMID- 23961215
TI  - Construction of a new GFP vector and its use for Fusaruim oxysporum
      transformation.
AB  - In this study, the gfp fragment as a reporter gene had integrated into the form
      plasmid vector pBC-hygro which contains an expressive promoter of the fungus to
      facilitate the transformation of Fusarium oxysporum. The resultant plasmid pBC
      hygro-GFP was identified by digestion with enzymes. Binary plasmids pBC-hygro-GFP
      were transformed into F. oxysporum by using the PEG-CaCl2 mediated transformation
      technique. Results show that the recombinant plasmid pBC-hygro-GFP was
      constructed correctly. The gfp gene was stably maintained and did not convey any
      significant loss of phenotype which would affect the survival and behaviour of
      the tagged strains. Introduction of the gfp gene into F. oxysporum provides a
      simple, specific and cost-effective method of strain identification for
      ecological studies. Transcriptional reporter vectors were constructed for using
      the green fluorescent protein (GFP) reporter. 

PMID- 23961216
TI  - Effect of lead stress on mineral content and growth of wheat (Triticum aestivum)
      and spinach (Spinacia oleracea) seedlings.
AB  - Lead (Pb) is the most common heavy metal contaminant in the environment. Pb is
      not an essential element for plants, but they absorb it when it is present in
      their environment, especially in rural areas when the soil is polluted by
      automotive exhaust and in fields contaminated with fertilizers containing heavy
      metal impurities. To investigate lead effects on nutrient uptake and metabolism,
      two plant species, spinach (Spinacia oleracea) and wheat (Triticum aestivum),
      were grown under hydroponic conditions and stressed with lead nitrate, Pb(NO3)2,
      at three concentrations (1.5, 3, and 15 mM). Lead is accumulated in a dose
      dependent manner in both plant species, which results in reduced growth and lower
      uptake of all mineral ions tested. Total amounts and concentrations of most
      mineral ions (Na, K, Ca, P, Mg, Fe, Cu and Zn) are reduced, although Mn
      concentrations are increased, as its uptake is reduced less relative to the whole
      plant's growth. The deficiency of mineral nutrients correlates in a strong
      decrease in the contents of chlorophylls a and b and proline in both species, but
      these effects are less pronounced in spinach than in wheat. By contrast, the
      effects of lead on soluble proteins differ between species; they are reduced in
      wheat at all lead concentrations, whereas they are increased in spinach, where
      their value peaks at 3 mM Pb. The relative lead uptake by spinach and wheat, and
      the different susceptibility of these two species to lead treatment are
      discussed. 

PMID- 23961217
TI  - An avifaunal survey of mesic manmade ecosystems "Oases" in algerian hot-hyperarid
      lands.
AB  - Man made ecosystems of dry lands are key habitats due to their ecological
      characteristics to survey biodiversity. This study investigated bird diversity in
      three oases of the Northern Algerian Sahara (i.e., Biskra in 2006, Oued Souf in
      2008 and Ouargla in 2009), by using the spot-mapping method. Bird density "D"
      (pairs/10 ha), species richness "S" (number species), diversity (Shannon index)
      "H'" (in bits), and evenness "E" varied from one oasis to another (Biskra: D =
      98.5, S = 47, H' = 4.49, E = 0.81; Oued Souf: D = 96, S = 33, H' = 3.9, E = 0.77;
      Ouargla: D = 91.5, S = 44, H' = 4.39, E = 0.80). Differences in bird diversity
      between the monitored palm groves are due to the ecological characteristics of
      each environment. Documented literature outlined close taxonomic similarities
      between bird assemblages of the study area with many Northern Saharan oases. The
      Hybrid Sparrow Passer domesticus x Passer. hispaniolensis and some Columbidae
      species including Columba livia, Streptopelia turtur, Streptopelia senegalensis,
      and Streptopelia decaocto were the abundant species throughout surveyed oases in
      which they represented more than half (55.6%) of the sum of species densities (D
      = 286 pairs/10 ha). These synthropic species have known a huge expansion of their
      distribution range throughout Algerian oases. The correspondence analysis allowed
      the aggregation of both families and species into oasis they belong to. One-way
      ANOVA was tested to analyse variations of both family and species densities
      between studied oases. The ANOVA revealed there was no significant variation
      either in family densities (p = 0.937) or in bird densities (p = 0.622) between
      the surveyed oases because of the small size of bird populations. 

PMID- 23961218
TI  - Evidence of apoptosis in some cell types due to pentachlorophenol (PCP) in
      Heteropneustes fossilis.
AB  - The study aimed to clarify the role of apoptosis in pentachlorophenol (PCP)
      induced testicular, ovarian and renal cell genotoxicity of Heteropneustes
      fossilis. It was further intended to find the target germ cell type and assess
      the cellular and nuclear damage. Treatment of PCP was used for multiduration on
      the germinal tissues and they were processed to detect structural changes by
      light and electron microscopic evaluation and kidney cells for subsequent
      detection of DNA fragmentation by agarose gel electrophoresis. Findings suggest
      functional and morphological changes in the tissues are due to apoptosis, as
      evidenced by some biochemical and cytological signs. Histological observation on
      germinal epithelium reveals cell suicidal symptoms such as vacuolization,
      liquefied regions in the cytoplasm of oocytes, margination of nuclei, clumping of
      chromatin, and compaction of cytoplasmic organelle. Biochemical manifestation
      concurrent to this, is; cleavage of kidney cell DNA into low molecular weight
      fragments confirming apoptosis. Subsequently, it is further cleaved into
      nucleosome size fragments or its multiples. Ultra-structural histopathology and
      DNA studies conclusively lead to the PCP induced apoptosis in the exposed cell
      types. Results further support the usefulness of this assay in the related
      studies and its feasibility in generating a base line data. 

PMID- 23961219
TI  - Detection of Fusarium wilt pathogens of Psidium guajava L. in soil using culture
      independent PCR (ciPCR).
AB  - Traditional culturing methods take a long time for identification of pathogenic
      isolates. A protocol has been developed for the detection of Fusarium from soil
      samples in the early stage of infection. Seventeen soil samples from different
      locations were collected before the onset of rains to find out the presence of
      Fusarium spp. population present in the soil of guava orchards and to correlate
      its presence with incidence of wilt. A PCR based method was developed for the
      molecular characterization of Fusarium using Fusarium spp. specific primer. DNA
      extracted by this method was free from protein and other contaminations and the
      yield was sufficient for PCR amplification. The primer developed in this study
      was amplifying ~230 bp in all infected samples while not in healthy soil. The
      specificity and sensitivity of primer were tested on several Fusarium spp. and
      found that this primer was amplifying 10(-6) dilution of the fungal DNA. The
      present study facilitates the rapid detection of Fusarium spp. from infected soil
      samples of guava collected from different agroclimatic regions in India. A rapid
      detection method for pathogens and a diagnostic assay for disease would
      facilitate an early detection of pathogen and lead to more effective control
      strategies. 

PMID- 23961220
TI  - Influence of inoculation with plant growth promoting rhizobacteria (PGPR) on
      tomato plant growth and nematode reproduction under greenhouse conditions.
AB  - Numerous species of soil bacteria which flourish in the rhizosphere of plants or
      around plant tissues stimulate plant growth and reduce nematode population by
      antagonistic behavior. These bacteria are collectively known as PGPR (plant
      growth promoting rhizobacteria). The effects of six isolates of PGPR Pseudomonas
      putida, Pseudomonas fluorescens, Serratia marcescens, Bacillus amyloliquefaciens,
      Bacillus subtilis and Bacillus cereus, were studied on tomato plant growth and
      root knot nematode reproduction after 45 days from nematode infection. The
      highest number of shoot dry weight/g (43.00 g) was detected in the plant treated
      with S. marcescens; then P. putida (34.33 g), B. amyloliquefaciens (31.66 g), P.
      fluorescens (30.0 g), B. subtilis (29.0 g), B. cereus (27.0 g) and nematode alone
      (untreated) 20 g/plant. While the highest number of plant height was observed
      when plant was treated with S. marcescens, P. fluorescens, P. putida, B.
      amyloliquefaciens and P. putida 52.66, 50.66, 48 and 48 cm respectively. No
      significant differences were seen between previous treatments but only had
      significant differences compared with untreated plant. The highest number of
      fruit/plant was observed when plants were treated with S. marcescens (10.66),
      then B. amyloliquefaciens (8.66), P. putida (8), P. fluorescens (8) and B. cereus
      (7.66). No significant differences between the last 4 treatments, but all had
      significant differences compared with untreated plants. The highest weight of
      plant yield (g) was observed with S. marcescens (319.6 g/plant) and the lowest
      weight of plant yield was observed in plants treated with nematode alone
      (untreated). On the other hand, the lowest numbers of J2/10 g of soil (78),
      galls/root, (24.33) galls/root, egg masses/root (12.66) and egg/egg masses were
      observed in the plants treated with S. marcescens. 

PMID- 23961221
TI  - In vitro micropropagation of Dracaena sanderiana Sander ex Mast: An important
      indoor ornamental plant.
AB  - A protocol has been developed for in vitro plant regeneration from a nodal
      explant of Dracaena sanderiana Sander ex Mast. Nodal explant showed high callus
      induction potentiality on MS medium supplemented with 6.78 MUM 2,4
      dichlorophenoxyacetic acid (2,4-D) followed by 46.5 MUM chlorophenoxy acetic acid
      (CPA). The highest frequency of shoot regeneration (85%) and number of shoots per
      explant (5.6) were obtained on medium supplemented with 7.84 MUM N(6)
      benzylaminopurine (BA). Rooting was high on MS solid compared to liquid medium
      when added with 7.38 MUM indole-3-butyric acid (IBA). Fifty percent of the roots
      were also directly rooted as microcuttings on soil rite, sand and peat mixture
      (1:1:1). In vitro and ex vitro raised plantlets were used for acclimatization.
      More than 90% of the plantlets was successfully acclimatized and established in
      plastic pots. Ex vitro transferred plantlets were normal without any phenotypic
      aberrations. 

PMID- 23961222
TI  - Anticariogenic and phytochemical evaluation of Eucalyptus globules Labill.
AB  - In the present study, in vitro anticariogenic potential of ethyl acetate, hexane
      and methanol and aqueous extracts of plant leaves of Eucalyptus globules Labill.
      were evaluated by using four cariogenic bacteria, Lactobacillus acidophilus,
      Lactobacillus casei, Staphylococcus aureus and Streptococcus mutans. Agar well
      diffusion method and minimum inhibitory concentration (MIC) were used for this
      purpose. The ethyl acetate extracted fraction of plant leaves showed good
      inhibitory effects against all selected bacteria. In Eucalyptus globules, hexane
      and ethyl acetate extracts found highly effective against, Lactobacillus
      acidophilus with MIC value of 0.031 and 0.062 mg/mL, respectively. Qualitative
      phytochemical investigation of above extracts showed the presence of alkaloids,
      phenolic compounds, steroids, cardiac glycosides and terpenes. Based on the MIC
      value and bioautography, ethyl acetate of plant leaf was selected for further
      study. Further investigation on the structure elucidation of the bioactive
      compound using IR, GC-MS and NMR techniques revealed the presence of alpha
      farnesene, a sesquiterpene. Eucalyptus globules plant leaf extracts have great
      potential as anticariogenic agents that may be useful in the treatment of oral
      disease. 

PMID- 23961223
TI  - Prevalence of Helicobacter pylori infection and the incidence of ureA and
      clarithromycin resistance gene 23S rRNA genotypes status in Saudi Arabia.
AB  - OBJECTIVES: To determine the prevalence of Helicobacter pylori ureA and
      clarithromycin resistance gene 23S rRNA genotypes among H. pylori in Saudi
      Arabia. METHODS: A total of 100 serum and fecal samples from 70 patients and 30
      healthy volunteers, from patients who presented with symptoms suggestive of
      gastritis or peptic ulcer disease, were taken from the main hospital in the
      Southern region of Saudi Arabia from September 2010 C.E. to March 2011 C.E.
      corresponding to Shawwal 1431 A.H. to Rabi Al-Thani 1432 A.H. We cultured the
      samples for H. pylori and a polymerase chain reaction was carried out to check
      for the presence or absence of ureA gene and clarithromycin resistance gene 23S
      rRNA genotypes. RESULTS: Among the 70 suspected patients, the suspected bacteria
      isolated from the fecal samples of 60, (85.7%) were positive using the culture
      techniques. The presence of ureA gene and clarithromycin resistance gene 23S rRNA
      was determined by using the polymerase chain reaction, Among the 100 fecal
      specimens, 65 fecal specimens from 70% patients showed positive results to
      clarithromycin resistance gene 23S rRNA (sensitivity, 93%; Specificity, 100% and
      Accuracy, 95%), Only 60 fecal specimens were positive with ureA gene
      (sensitivity, 86%; Specificity, 100% and Accuracy, 90%). CONCLUSION: 23S rRNA
      gene was associated with clarithromycin resistance in H. pylori. There was a high
      prevalence of H. pylori resistance to clarithromycin in Saudi Arabia. H. pylori
      is a neutrophilic bacteria that has been able to colonize the human stomach by
      using a variety of acid-adaptive mechanisms as Urease activity that hydrolyzed
      the Urea producing 2 NH3 and H2CO3.

PMID- 23961224
TI  - In vitro trials of some antimicrobial combinations against Staphylococcus aureus
      and Pseudomonas aeruginosa.
AB  - Staphylococcus aureus and Pseudomonas aeruginosa are rapidly increasing as
      multidrug resistant strains worldwide. In nosocomial settings because of heavy
      exposure of different antimicrobials, resistance in these pathogens turned into a
      grave issue in both developed and developing countries. The aim of this study was
      to investigate in vitro antibiotic synergism of combinations of beta-lactam-beta
      lactam and beta-lactam-aminoglycoside against clinical isolates of S. aureus and
      P. aeruginosa. Synergy was determined by checkerboard double dilution method. The
      combination of amoxicillin and cefadroxil was found to be synergistic against 47
      S. aureus isolates, in the FICI range of 0.14-0.50 (81.03%) followed by the
      combination of streptomycin and cefadroxil synergistic against 44 S. aureus
      isolates in the FICI range of 0.03-0.50 (75.86%). The combination of streptomycin
      and cefadroxil was observed to be synergistic against 39 P. aeruginosa isolates
      in the FICI range of 0.16-0.50 (81.28%). Further actions are needed to
      characterize the possible interaction mechanism between these antibiotics.
      Moreover, the combination of streptomycin and cefadroxil may lead to the
      development of a new and vital antimicrobial against simultaneous infections of
      S. aureus and P. aeruginosa. 

PMID- 23961225
TI  - Antibiofilm activity of coconut (Cocos nucifera Linn.) husk fibre extract.
AB  - In this study, antibiofilm activity of coconut husk extract (CHE) was tested by
      various assays in the laboratory. The effects of CHE on extracellular polymeric
      substance (EPS) production, hydrophobicity and adhesion ability of Pseudomonas
      sp., Alteromonas sp. and Gallionella sp. and the antimicrobial activity of the
      extract against these bacteria were assessed. CHE was found to possess
      antibacterial activity against all the bacterial strains and affected the EPS
      production. The CHE affected the growth of the biofilm-forming bacteria in a
      culture medium. The hydrophobicity of the bacterial cells was also changed due to
      the CHE treatment. The active compound of the CHE was characterised by thin-layer
      chromatography (TLC), high performance liquid chromatography (HPLC) and fourier
      transform infrared (FT-IR) analysis. HPLC spectrum showed a single peak and the
      FT-IR spectrum indicated the presence of an OH-group-containing compound in the
      extract. In conclusion the CHE could be used as a source for the isolation of
      antifouling compounds. 

PMID- 23961226
TI  - Molt cycle related changes and effect of short term starvation on the biochemical
      constituents of the blue swimmer crab Portunus pelagicus.
AB  - Synthesis and hardening of a new exoskeleton are essential to the arthropod
      molting process. The present study emphasizes the variations in the levels of
      hemolymph total free sugars, hepatopancreas glycogen and cuticular proteins
      during the molting stages of Portunus pelagicus. It also reports the effect of
      short-term starvation conditions on the biochemical constituents of the
      hemolymph. Intermolt crabs were subjected to 6 days of starvation and hemolymph
      samples were taken. Standard biochemical procedures were followed toward the
      quantification of total proteins, total free sugars and total lipids. The total
      free sugar level in the hemolymph of P. pelagicus was observed to increase during
      early premolt D0 (3.108 +/- 0.032 g/ml) and a gradual decrease till late postmolt
      B stage (0.552 +/- 0.124 g/ml), suggesting the need for total free sugars to
      provide energy for the apolysis process. Increase in the levels of hepatopancreas
      glycogen was observed from 1225 +/- 0.04 MUg/mg in early premolt D0 to 1700 +/-
      0.3 MUg/mg in late premolt D2-3. This is in correlation with the decreased levels
      of free sugars during premolt stages, suggesting an increase in the storage of
      glycogen reserves in the hepatopancreas. Cuticular proteins increased during
      stage B (2.702 +/- 0.093 g/ml) and stage C (3.065 +/- 0.012 g/ml), indicating
      exoskeleton hardening and mineralization. Results of the starvation studies
      clearly showed a steady decline in the level of total free sugars till day 6
      (0.099 +/- 0.00 g/ml) when compared to the control (8.646 +/- 0.08 g/ml). Gradual
      decrease of total lipids was also observed from the first day of the experiment
      (6.088 +/- 2.44 g/ml) to the last day of the study (0.401 +/- 0.20 g/ml) which
      was 85% lesser than the control (8.450 +/- 0.49 g/ml)suggesting the efficient
      usage of total sugars to consolidate the loss of energy reserves during
      starvation. The knowledge of Molt-cycle events can be used as a tool for the
      evaluation of the developmental state providing a morphological reference system
      for physiological and biochemical studies related to crab aquaculture. Starvation
      studies enlightens that increasing carbohydrate levels in crab feed together with
      good protein content could alleviate the natural effects of starvation, improve
      farm productivity and reduce the deleterious impact of nitrogen pollution
      generated by rich-protein feeds used in crab farming. 

PMID- 23961227
TI  - Valorization of date palm (Phoenix dactylifera) fruit processing by-products and
      wastes using bioprocess technology - Review.
AB  - The date palm Phoenix dactylifera has played an important role in the day-to-day
      life of the people for the last 7000 years. Today worldwide production,
      utilization and industrialization of dates are continuously increasing since date
      fruits have earned great importance in human nutrition owing to their rich
      content of essential nutrients. Tons of date palm fruit wastes are discarded
      daily by the date processing industries leading to environmental problems. Wastes
      such as date pits represent an average of 10% of the date fruits. Thus, there is
      an urgent need to find suitable applications for this waste. In spite of several
      studies on date palm cultivation, their utilization and scope for utilizing date
      fruit in therapeutic applications, very few reviews are available and they are
      limited to the chemistry and pharmacology of the date fruits and phytochemical
      composition, nutritional significance and potential health benefits of date fruit
      consumption. In this context, in the present review the prospects of valorization
      of these date fruit processing by-products and wastes' employing fermentation and
      enzyme processing technologies towards total utilization of this valuable
      commodity for the production of biofuels, biopolymers, biosurfactants, organic
      acids, antibiotics, industrial enzymes and other possible industrial chemicals
      are discussed. 

PMID- 23961228
TI  - Apoptosis and necrosis of human breast cancer cells by an aqueous extract of
      garden cress (Lepidium sativum) seeds.
AB  - Conventional treatments for breast cancer are costly and have serious side
      effects. Non-conventional natural treatments have gained wide acceptance due to
      their promise of a cure with minimal or no side effects, but little scientific
      evidence exists. One such common remedy is the seed of the Lepidium sativum
      plant. Presented here is the first reported use of the aqueous extract of
      Lepidium sativum seeds on breast cancer cells. The ability of the extract to
      induce apoptosis and necrosis in the human breast cancer cell line MCF-7,
      compared to normal human skin fibroblasts (HFS), was determined by morphological
      changes in the cells using light microscopy, DNA fragmentation assay, and
      florescent stains (Annexin V and propidium iodide) using flow cytometry and
      fluorescent microscopy. Apoptosis was induced in both cells, and more in MCF-7,
      when they were treated with 25% and 50% extract, while necrosis was observed
      mainly after exposure to elevated extract concentrations (75%). DNA fragmentation
      resulted for both cells, in a time and dose-dependent manner. Both cells, at all
      extract concentrations, showed no significant differences in the number of
      living, dead, apoptotic, and necrotic cells. Finally, the results may indicate
      that apoptotic changes in MCF-7 may be independent of caspase-3, which is
      involved in apoptosis and is lacking in MCF-7 cells. 

PMID- 23961229
TI  - Effect of GA3 and 2,4-D foliar application on the anatomy of date palm (Phoenix
      dactylifera L.) seedling leaf.
AB  - Two concentrations (10-5M and 10-3M) of both GA3 and 2,4-D were used as foliar
      spray to evaluate the response of date palm (Phoenix dactylifera L.) cv. Khedri
      seedlings. They affected some of the anatomical characteristics of the first leaf
      emerging after the beginning of the spray. The high concentration of GA3
      increased the size of the midrib and its vascular bundle numbers. Both low and
      high concentrations of 2,4-D inhibited the formation of the midrib. 2,4-D in both
      low and high concentrations decreased the number of vessels in both protoxylem
      and metaxylem and also decreased their diameters, where as GA3 in low and high
      concentrations have less effect on the number of vessels and its diameters. GA3
      in high concentration increased the number of vascular bundles in 1mm long of the
      leaf blade, while 2,4-D in low and high concentrations decreased their numbers.
      10-3M of 2,4-D increased the size and layers of special hypodermal cells. 

PMID- 23961230
TI  - Bioconversion of garden waste, kitchen waste and cow dung into value-added
      products using earthworm Eisenia fetida.
AB  - Solid waste management is a worldwide problem and it is becoming more and more
      complicated day by day due to rise in population, industrialization and changes
      in our life style. Transformation of industrial sludges into vermicompost is of
      double interest: on the one hand, a waste is converted into value added product,
      and, on the other, it controls a pollutant that is a consequence of increasing
      industrialization. Garden waste, kitchen waste and cow dung were subjected to
      recycle through vermicomposting by using the epigeic earthworm Eisenia fetida
      under field conditions. The pH, moisture content, total organic carbon, humus,
      nitrogen, phosphorous and potassium in vermicompost was analysed. It was found
      that moisture content, total organic carbon, humus, nitrogen, phosphorous and
      potassium was high in cow dung, followed by kitchen waste and garden waste. This
      study clearly indicates that vermicomposting of garden waste, kitchen waste and
      cow dung can not only produce a value added produce (vermicomposting) but at the
      same time reduce the quantity of waste. 

PMID- 23961232
TI  - gamma Actinorhodin a natural and attorney source for synthetic dye to detect acid
      production of fungi.
AB  - Colors from natural sources are gaining popularity because synthetic colors are
      carcinogenic. Natural colors are obtained from plants or microorganisms. Pigments
      produced by microorganisms have advantages over plant pigments, due to their ease
      of use and reliability. In the present study, a blue pigment producing
      actinomycete klmp33 was isolated from the Gulbarga region in India. The isolate
      was identified based on morphologic, microscopic, and biochemical
      characterization, and 16S rRNA sequencing. Phylogenetic analysis of the isolates
      showed a close relationship with Streptomyces coelicolor. Pigment produced by the
      isolate was analyzed using UV-visible spectroscopy, thin-layer chromatography,
      Fourier transform infrared and liquid chromatography/mass spectroscopy analysis,
      and was identified as gamma actinorhodin. gamma-Actinorhodin is used as a pH
      indicator which deviates from acid to non-acid. Moreover, it subrogates synthetic
      dye. 

PMID- 23961231
TI  - Protective effects of curcumin against lithium-pilocarpine induced status
      epilepticus, cognitive dysfunction and oxidative stress in young rats.
AB  - Status epilepticus (SE), one of the most severe forms of epilepsy is regarded a
      medical emergency with considerable morbidity and mortality. Due to the limited
      efficacy and enormous side effects of currently available drugs, a search for new
      safe and effective therapeutic agents is critical using experimentally induced SE
      in animals. The lithium-pilocarpine (Li-Pc) model of SE is most suitable and
      frequently used for pathophysiological and management strategies of SE. Recent
      studies have shown significant potential of pharmacological, prophylactic or
      therapeutic use of curcumin (Cur) in many beneficial activities in the body
      including neuroprotection in neurodegenerative diseases and antioxidant
      properties. The present study describes anticonvulsive effects of Cur in Li-Pc
      induced SE in young rats. The effect of Cur was examined on the intensity and
      frequency of SE, cognitive behavior in water maze as well as on oxidative stress
      related enzymes in the brain. Besides its anticonvulsant effect, Cur
      significantly ameliorates SE-induced cognitive dysfunction and oxidative damages
      in the hippocampus and striatum areas of the brain. Possible therapeutic
      application of Cur as an anticonvulsant and as an antioxidant for the treatment
      of SE has a great potential and warrants further studies. 

PMID- 23961233
TI  - Performance study of biofilter developed to treat H2S from wastewater odour.
AB  - Biofiltration is an efficient biotechnological process used for waste gas
      abatement in various industrial processes. It offers low operating and capital
      costs and produces minimal secondary waste streams. The objective of this study
      was to evaluate the performance of a pilot scale biofilter in terms of
      pollutants' removal efficiencies and the bacterial dynamics under different inlet
      concentrations of H2S. The treatment of odourous pollutants by biofiltration was
      investigated at a municipal wastewater treatment plant (WWTP) (Charguia, Tunis,
      Tunisia). Sampling and analyses were conducted for 150 days. Inlet H2S
      concentration recorded was between 200 and 1300 mg H2S.m(-3). Removal
      efficiencies reached 99% for the majority of the running time at an empty bed
      retention time (EBRT) of 60 s. Heterotrophic bacteria were found to be the
      dominant microorganisms in the biofilter. The bacteria were identified as the
      members of the genus Bacillus, Pseudomonas and xanthomonadacea bacterium. The
      polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP)
      method showed that bacterial community profiles changed with the H2S inlet
      concentration. Our results indicated that the biofilter system, containing peat
      as the packing material, was proved able to remove H2S from the WWTP odourous
      pollutants. 

PMID- 23961234
TI  - The gold nanoparticle size and exposure duration effect on the liver and kidney
      function of rats: In vivo.
AB  - Nanoparticles (NPs) offer a great possibility for biomedical application, not
      only to deliver pharmaceutics, but also to be used as novel diagnostic and
      therapeutic approaches. Currently, there are no data available regarding to what
      extent the degree of the toxicity and the accumulation of gold nanoparticles
      (GNPs) are present in in vivo administration. This study aimed to address the GNP
      size and exposure duration effect on the liver and kidney function of rats: in
      vivo. METHODS: A total of 30 healthy male Wistar-Kyoto rats of the same age (12
      weeks old) and weighing 220-240 g of King Saud University colony were used.
      Animals were randomly divided into groups, two GNP-treated rat groups and one
      control group (CG). The 50 MUl of 10 and 50 nm GNPs was intraperitoneally
      administered in rats for exposure duration of 3 days. Then, several biochemical
      parameters such as aspartate aminotransferase (AST), gamma-glutamyl transferase
      (GGT), alanine transaminase (ALT), alkaline phosphatase (ALP), urea (UREA) and
      creatinine (CREA) were evaluated. RESULTS: In this study, the AST values
      increased with the administration of 10 and 50 nm GNPs compared with the control.
      The AST values significantly increased with 10 nm GNPs compared with 50 nm GNPs
      and control. The GGT and ALT values decreased with the administration of 10 and
      50 nm GNPs compared with the control. The GGT and ALT values significantly
      decreased with 50 nm GNPs compared with 10 nm GNPs and control. The ALP values
      significantly decreased with the administration of 10 and 50 nm GNPs compared
      with the control. The decrease in ALP values with 10 nm GNPs was higher than
      those compared with 50 nm GNPs. In this study, the levels of UREA and CREA values
      increased in a non significant manner after the administration of 10 and 50 nm
      GNPs compared with the control. CONCLUSIONS: This study demonstrates that the
      increase in the enzymes AST and the decrease in ALP are smaller GNPs (10 nm) size
      dependent for exposure duration of 3 days; while the decrease in the enzymes GGT
      and ALT are bigger GNPs (50 nm) size-dependent. The levels of UREA and CREA
      values indicated no significant changes with the administration of 10 and 50 nm
      GNPs for exposure duration of 3 days compared with the control. The
      administration of 10 and 50 nm GNPs for short exposure duration of 3 days induced
      only significant variations with some liver enzymes while kidney showed no
      significant variations. This study suggests that synthesis and metabolism of GNPs
      as well as the protection of the liver will be more important issues for medical
      applications of gold-based nanomaterials in future.

PMID- 23961235
TI  - Salt-induced modulation in growth, photosynthesis and antioxidant system in two
      varieties of Brassica juncea.
AB  - The present study was carried out to examine salt-induced modulation in growth,
      photosynthetic characteristics and antioxidant system in two cultivars of
      Brassica juncea Czern and Coss varieties (Varuna and RH-30). The surface
      sterilized seeds of these varieties were sown in the soil amended with different
      levels (2.8, 4.2 or 5.6 dsm(-1)) of sodium chloride under a simple randomized
      block design. The salt treatment significantly decreased growth, net
      photosynthetic rate and its related attributes, chlorophyll fluorescence, SPAD
      value of chlorophyll, leaf carbonic anhydrase activity and leaf water potential,
      whereas electrolyte leakage, proline content, and activity of catalase,
      peroxidase and superoxide dismutase enzymes increased in both the varieties at 30
      d stage of growth. The variety Varuna was found more resistant than RH-30 to the
      salt stress and possessed higher values for growth, photosynthetic attributes and
      antioxidant enzymes. Out of the graded concentrations (2.8, 4.2 or 5.6 dsm(-1))
      of sodium chloride, 2.8 sm(-1) was least toxic and 5.6 dsm(-1) was most harmful.
      The variation in the responses of these two varieties to salt stress is
      attributed to their differential photosynthetic traits, SPAD chlorophyll value
      and antioxidant capacity, which can be used as potential markers for screening
      mustard plants for salt tolerance. 

PMID- 23961236
TI  - Investigation on Plasmodium falciparum and Plasmodium vivax infection influencing
      host haematological factors in tribal dominant and malaria endemic population of
      Jharkhand.
AB  - The study was undertaken to elucidate the association of host haematological and
      biochemical indices in Plasmodium falciparum and Plasmodium vivax malaria in
      order to explore whether these parameters are unique to disease or act as a
      potential diagnostic marker. Haematological and biochemical parameters in 106
      malarial patients and 33 healthy subjects were evaluated. Following parameters
      were significantly lower in all infection types (P. vivax, P. falciparum and
      mixed infection); haemoglobin, blood sugar, PCV and blood urea, while ESR is
      significantly higher in all types of infection whereas serum bilirubin and
      creatinine are significantly higher except mixed and vivax infection,
      respectively. Interestingly, parasitaemia, temperature and age are significantly
      correlated with blood urea, blood sugar and ESR respectively in vivax infection
      whereas parasitaemia with PCV and blood sugar and age with PCV in falciparum
      infection. Malaria infected subjects exhibited alterations in some haematological
      parameters with low haemoglobin, blood sugar and PCV whereas elevated ESR and
      serum bilirubin being the important findings observed in our study. These
      evaluations could be considered to be reliable clinical and biochemical markers
      for promising diagnostic potential during clinical malarial infection in
      combination with other genetic and classical microscopic parameters.
      Haematological evaluation could help in prompt and accurate diagnosis and prevent
      disease progression by facilitating physicians in clinical correlation for better
      drug regime. 

PMID- 23961237
TI  - Halocin SH10 production by an extreme haloarchaeon Natrinema sp. BTSH10 isolated
      from salt pans of South India.
AB  - Halobacteria, members of the domain Archaea that live under extremely halophilic
      conditions, are often considered as dependable source for deriving novel enzymes,
      novel genes, bioactive compounds and other industrially important molecules.
      Protein antibiotics have potential for application as preserving agents in food
      industry, leather industry and in control of infectious bacteria. Halocins are
      proteinaceous antibiotics synthesized and released into the environment by
      extreme halophiles, a universal characteristic of halophilic bacteria. Herein, we
      report the production of halocin (SH10) by an extremely halophilic archeon
      Natrinema sp. BTSH10 isolated from salt pan of Kanyakumari, Tamilnadu, India and
      optimization of medium for enhanced production of halocin. It was found that the
      optimal conditions for maximal halocin production were 42  degrees C, pH 8.0, and
      104 h of incubation at 200 rpm with 2% (V/V) inoculum concentration in Zobell's
      medium containing 3 M NaCl, Galactose, beef extract, and calcium chloride as
      additional supplements. Results indicated scope for fermentation production of
      halocin for probable applications using halophilic archeon Natrinema sp. BTSH10. 

PMID- 23961238
TI  - Antioxidative, antimicrobial and cytotoxic effects of the phenolics of Leea
      indica leaf extract.
AB  - This study investigated the phytochemical, antioxidative, antimicrobial and
      cytotoxic effects of Leea indica leaf ethanol extract. Phytochemical values
      namely total phenolic and flavonoid contents, total antioxidant capacity, DPPH
      radical scavenging effect, FeCl3 reducing power, DMSO superoxide scavenging
      effect and Iron chelating effects were studied by established methods.
      Antibacterial, antifungal and cytotoxic effects were screened by disk diffusion
      technique, food poison technique and brine shrimp bioassay, respectively. Results
      showed the total phenolic content 24.00 +/- 0.81 g GAE/100 g, total flavonoid
      content 194.68 +/- 2.43 g quercetin/100 g and total antioxidant capacity 106.61
      +/- 1.84 g AA/100 g dry extract. Significant (P < 0.05) IC50 values compared to
      respective standards were recorded in DPPH radical scavenging (139.83 +/- 1.40
      MUg/ml), FeCl3 reduction (16.48 +/- 0.64 MUg/ml), DMSO superoxide scavenging
      (676.08 +/- 5.80 MUg/ml) and Iron chelating (519.33 +/- 16.96 MUg/ml) methods. In
      antibacterial screening, the extract showed significant (P < 0.05) zone of
      inhibitions compared to positive controls Ampicillin and Tetracycline against
      Gram positive Bacillus subtilis, Bacillus cereus, Bacillus megaterium, and
      Staphylococcus aureus and Gram negative Salmonella typhi, Salmonella paratyphi,
      Pseudomonas aeroginosa, Shigella dysenteriae, Vibrio cholerae, and Escherichia
      coli. Significant minimum inhibitory concentrations compared to tetracycline were
      obtained against the above organisms. In antifungal assay, the extract inhibited
      the growth of Aspergillus flavus, Candida albicans and Fusarium equisetii by
      38.09 +/- 0.59, 22.58 +/- 2.22, and 22.58 +/- 2.22%, respectively. The extract
      showed a significant LC50 value compared to vincristine sulfate in cytotoxic
      assay. The results evidenced the potential antioxidative, antimicrobial and
      cytotoxic capacities of Leea inidica leaf extract to be processed for
      pharmaceutical use. 

PMID- 23961239
TI  - Evaluation of in vitro free radical scavenging potential of Streptomyces sp. AM
      S1 culture filtrate.
AB  - The present study was carried out to determine the free radical scavenging
      potential of culture filtrate of Streptomyces sp. AM-S1. Antioxidant activity of
      culture filtrate, lyophilized culture filtrate and ethyl acetate extract of
      Streptomyces sp. AM-S1 was determined by various in vitro assays such as ferric
      reducing power assay, phosphomolybdenum reduction, DPPH and ABTS radical
      scavenging activities. The results revealed that the culture filtrate of
      Streptomyces sp. AM-S1 effectively scavenged DPPH (IC50 90.2 MUl/ml) and ABTS
      (IC50 13.2 MUl/ml) radicals in a concentration dependent manner. In all the
      assays, ethyl acetate extract registered higher antioxidant activity when
      compared with the lyophilized culture filtrate (LCF). In addition, ethyl acetate
      extract (1123.4 MUmole Fe(II)/mg extract) exhibited higher ferric reducing
      activity than the standard BHA (814.4 MUmole Fe(II)/mg extract). Further works
      are needed on the isolation and identification of antioxidant molecules from the
      ethyl acetate extract of Streptomyces sp. AM-S1 culture filtrate. 

PMID- 23961240
TI  - Free radical scavenging activity, total phenolic content, total antioxidant
      status, and total oxidant status of endemic Thermopsis turcica.
AB  - Thermopsis turcica, endemic to Turkey, is in danger of extinction. Studies on
      this species are very few due to the fact that it was only discovered in 1983 and
      grows in a small circumscribed area in Turkey. In this study, free radical
      scavenging activity, total phenolic content, total oxidant status (TOS), and
      total antioxidant status (TAS) of methanol (TTM) and acetone (TTA) extracts of T.
      turcica were measured spectroscopically. Free radical scavenging activity was
      determined according to the elimination of DPPH radicals and total phenol content
      was determined by the Folin-Ciocalteu reaction. Total oxidant status (TOS) and
      total antioxidant status (TAS) were measured with commercially available kits.
      Methanol and acetone extracts of T. turcica were found to have a specific radical
      scavenging effect. This effect was found to be related to the total phenolic
      content of the extracts. Since the TTA had a higher phenolic content than the
      methanol extract, it had a stronger radical scavenging effect. In addition, the
      total antioxidant capacity of the methanol extract was observed to be higher than
      that of its acetone counterpart. As a result, due to its antioxidative
      properties, T. turcica is thought to be a natural source of antioxidants. 

PMID- 23961241
TI  - Development of permethrin resistance in Culex quinquefasciatus Say in Kuala
      Lumpur, Malaysia.
AB  - The resistance status towards permethrin among the laboratory strain, the
      permethrin-selected strain and four field strains of Culex quinquefasciatus
      collected in Kuala Lumpur, Malaysia was determined using three standard
      laboratory methods: WHO larval bioassay, WHO adult bioassay and biochemical
      microplate assay. Cx. quinquefasciatus permethrin-selected strain larvae were the
      least susceptible to permethrin with a resistance ratio of 47.28-folds, whereas
      all field strain larvae of the same species were tolerant to permethrin with
      resistance ratios of more than 3-folds. In contrast, in adult stage, the
      permethrin exposed permethrin-selected strain (resistance ratio = 1.27) was found
      to be more susceptible to permethrin than all permethrin-exposed field strains
      (resistance ratios = 2.23-2.48). Complete mortalities for all strains of Cx.
      quinquefasciatus adults proved the effectiveness of the synergist; piperonyl
      butoxide (PBO). For the biochemical microplate assay, the reduction of the mean
      optical density of elevated oxidase activity of three field strains upon exposure
      to PBO confirmed the association between oxidase activity and permethrin
      tolerance. On the other hand, irregular patterns of the mean optical density of
      elevated oxidase activity in the laboratory strain, permethrin-selected strain
      and Jalan Fletcher strain illustrated the gene variation within these mosquito
      colonies as well as the involvement of other enzyme activities in the permethrin
      resistance occurred. 

PMID- 23961242
TI  - Optimization of multiple shoot induction and plant regeneration in Indian barley
      (Hordeum vulgare) cultivars using mature embryos.
AB  - Barley is the fourth most important crop in the world. Development of a
      regeneration system using immature embryos is both time consuming and laborious.
      The present study was initiated with a view to develop a regeneration system in
      six genotypes of Indian barley (Hordeum vulgare) cultivars as a prerequisite to
      transformation. The mature embryos were excised from seeds and cultured on MS
      medium supplemented with high and low concentrations of cytokinins and auxins
      respectively. The MS medium containing 3 mg/L N(6)-benzylaminopurine (BA) and 0.5
      mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) was found to be the most effective
      for multiple shoot formation in HOR7231 cultivar that could produce 12 shoots per
      explant. The other cultivars HOR4409 and HOR3844 produced a minimum number of
      adventitious shoots (1.33 and 1.67 respectively) on MS medium supplemented with 1
      mg/L BA and 0.3 mg/L 2,4-D. The elongated shoots were separated and successfully
      rooted on MS medium containing 1 mg/L indole-3-acetic acid (IAA). The response of
      different barley cultivars was found to be varying with respect to multiple shoot
      production. This is the first report of multiple shoot induction and plantlet
      regeneration in Indian cultivar of barley which would be useful for genetic
      transformation. 

PMID- 23961243
TI  - Comparative assessment of growth and biodegradation potential of soil isolate in
      the presence of pesticides.
AB  - In Pakistan, to increase agricultural production, higher amounts of fertilizers
      and pesticides are being used. The residues of the applied pesticides stay in the
      environment and therefore causing contamination of air, water and land. Moreover,
      agricultural industries are also contributing relatively high quantities of toxic
      pesticides into the environment. Since most of them have no treatment facilities.
      These pesticides may be toxic, mutagenic or carcinogenic. They may be
      bioaccumulated or biomagnified by the biota. Therefore its removal from
      environmental systems needs special attention. In this study, bacterial isolate,
      Pseudomonas, designated as IES-Ps-1, was used to assess its potential for
      pesticide removal from industrial wastewater using the biosimulator (activated
      sludge process). During experimental studies conducted in the flask as well as in
      biosimulator, it was observed that IES-Ps-1 grows normally at low concentrations
      of added insecticides when compared with the control test (without pesticide).
      However, at high concentrations the microbial count decreased but no death
      occurred and the culture remained in lag phase. In many cases, the growth of
      organisms in the presence of the particular substrate serves as an indication
      about its metabolic potential. However, to confirm these results, chemical oxygen
      demand (COD) and HPLC analysis were performed. Under aerobic culture conditions
      using mechanical aerators in biosimulator, almost complete removal of
      Cypermethrin at 20 mg/L dose occurred during 48 h. The study findings indicate
      that IES-Ps-1 strain, can be used for the treatment of the pesticide contaminated
      environment. Such study may be valuable to scientist and engineers, who are
      trying to develop methods for the treatment of toxic organic waste using the
      biological treatment process. 

PMID- 23961245
TI  - In vivo and in vitro studies on apoptosis in OSE cells and inclusion cysts of
      pregnant heifers.
AB  - Elevated progesterone concentration during pregnancy and use of progesterone-like
      contraceptives are known to reduce ovarian cancers. This study was undertaken to
      decipher whether or not there is any relationship between progesterone (also
      oestrogen)-mediated ovarian surface epithelium (OSE) apoptosis and expression of
      p53, a cell-cycle arresting protein and potential tumour suppressor.
      Immunohistochemical staining with cytokeratin confirmed epithelial nature of the
      cells in the OSE layer and inclusion cysts that invaginate inside stroma after
      ovulation takes place. The in situ apoptosis index was determined during oestrus,
      and at mid and late-pregnancy stages in heifers. Epithelia of both tissues
      exhibited significantly high nuclear staining, suggesting that these cells are
      aiming to apoptotic destruction. To further establish a role of progesterone, the
      OSE cells were exposed in vitro to two concentrations of oestrogen and
      progesterone. It was revealed that progesterone at both concentrations and
      oestrogen only at high concentration converted a large proportion of these cells
      apoptotic. The stimulatory effect of progesterone (and to some extent oestrogen)
      was also seen on p53 expression in the same cultivated OSE cells. The steroid
      dosage dependence for apoptosis and p53 expression was also somewhat similar.
      Assuming that progesterone action is mediated through p53-caused apoptosis as a
      mechanism to evade malignant transformation of OSE cells, p53 expression at mRNA
      and protein level was investigated in the OSE layer in proximity to stroma,
      antrum and corpus luteum (CL). In cycling animals CL produces a large amount of
      progesterone and also oestrogen to maintain the post-ovulatory cycle and to
      suppress the gonadotropin production. Hence, cells undergoing re
      epithelialization and which are in contact with CL were expected to undergo
      maximum apoptotic modification. Indeed we got the maximum p53/p53 gene expression
      in these cells. We conclude that progesterone during cycling and pregnancy may
      reduce the risk of developing ovarian cancer by ceasing cell cycle and diverting
      damaged and mutagenized OSE cells for apoptosis, and the process may be mediated
      through elevated p53 synthesis. However, it is also possible that progesterone
      and p53-induced apoptosis may be entirely different cancer suppressive actions
      but coincidently happening together. 

PMID- 23961244
TI  - Histopathology and cytotoxicity as biomarkers in treated rats with cadmium and
      some therapeutic agents.
AB  - The present study aimed to investigate the protective role of ascorbic acid
      (vitamin C) and zinc (Zn) against cadmium (Cd) induced histopathological changes
      in tissues of liver, kidney, lung and testis of rats as well as chromosomal
      aberrations. For this purpose, 60 male albino rats were divided into six groups;
      each group contained 10 animals. The first group served as control and was given
      only distilled water. The second and third groups received distilled water
      supplemented with 2 g ascorbic acid/l and 500 mg Zn/l, respectively. The fourth
      group received a daily oral dose containing 3 mg Cd/kg b.w. (1/30 LD50). The
      fifth group received Cd + ascorbic acid (3 mg Cd/kg b.w. + 2 g ascorbic acid/l),
      while the sixth group received Cd + Zn (3 mg Cd/kg b.w. +500 mg Zn/l). The
      treatment in all groups lasted for 90 consecutive days. Rats exposed to cadmium
      showed severe histopathological changes in the liver, kidney, lung and testicular
      tissues as well as chromosomal aberrations such as: break, ring, centromeric
      separation and polyploidy. Co-treatment with zinc partially improved the
      histopathological changes and chromosomal aberrations while co-treatment with
      vitamin C exhibited a more protective role and markedly reduced tissues damage
      induced by Cd. 

PMID- 23961246
TI  - Weed vegetation ecology of arable land in Salalah, Southern Oman.
AB  - This paper applies multivariate statistical methods to a data set of weed releves
      from arable fields in two different habitat types of coastal and mountainous
      escarpments in Southern Oman. The objectives were to test the effect of
      environmental gradients, crop plants and time on weed species composition, to
      rank the importance of these particular factors, and to describe the patterns of
      species composition and diversity associated with these factors. Through the
      application of TWINSPAN, DCA and CCA programs on data relating to 102 species
      recorded in 28 plots and farms distributed in the study area, six plant
      communities were identified: I- Dichanthium micranthum, II- Cynodon dactylon-D.
      micranthum, III- Convolvulus arvensis, IV- C. dactylon-Sonchus oleraceus, V-
      Amaranthus viridis and VI- Suaeda aegyptiaca-Achyranthes aspera. The ordination
      process (CCA) provided a sequence of plant communities and species diversity that
      correlated with some anthropogenic factors, physiographic variables and crop
      types. Therefore, length of time since farm construction, disturbance levels and
      altitude are the most important factors related to the occurrence of the species.
      The perennial species correlated with the more degraded mountain areas of new
      farm stands, whereas most of the annuals correlated with old lowland and less
      disturbed farms. 

PMID- 23961247
TI  - Good bye general.

PMID- 23961248
TI  - Left Ventricular Dyssynchrony Parameters Measured by Phase Analysis of Post
      stress and Resting Gated SPECT Myocardial Perfusion Imaging.
AB  - Phase analysis has been validated to measure left ventricular (LV) dyssynchrony
      from resting gated SPECT myocardial perfusion imaging (MPI). In 1-day rest/stress
      protocols, often only post-stress gated data are acquired. The purpose of this
      study was to determine whether LV dyssynchrony parameters measured at post-stress
      significantly differ from those measured at rest. Sixty normal subjects, 40
      patients with stress-induced ischemia but normal LV function, and 29 patients
      with LV dysfunction were included in this study. All patients were scanned using
      a 2-day Technetium-99m sestamibi (MIBI) MPI protocol, where gated SPECT data were
      acquired at 60 min post injection of the radiotracer. LV dyssynchrony parameters
      at post-stress and at rest were calculated and compared using paired t-test.
      There were no significant differences in the LV dyssynchrony parameters between
      post-stress and resting in all cohorts. No patient showed differences in the LV
      dyssynchrony parameters between the post-stress and resting scans significantly
      greater than the reported variations in these parameters between serial resting
      scans. There was no significant difference in dyssynchrony parameters measured at
      rest and 60 min after stress on MPI gated images. 

PMID- 23961249
TI  - (99m)Tc-MIBI Whole Body Scan: A Potentially Useful Technique for Evaluating
      Metabolic Bone Disease.
AB  - Metabolic bone disease due to hyperparathyroidism is characterized by increased
      bone resorption and new bone formation. (99m)Tc- hexakis-2
      methoxyisobutylisonitrile ((99m)Tc MIBI) accumulation is controlled by metabolic
      function and cell viability. To investigate, for the first time, the potential of
      whole body (99m)Tc MIBI scan for detecting, visually and with the aid of
      quantitative analysis, bony changes associated with hyperparathyroidism. Eighty
      six patients with hyperparathyroidism, referred routinely for parathyroid
      localization, were included in this case-control prospective study. Each patient
      was injected with 20-25 mCi of (99m)Tc MIBI. Routine anterior cervico-thoracic
      images were obtained for parathyroid localization. Two extra whole body images
      were acquired and assessed visually and by drawing regions of interest over the
      mandible, sternum, femur, humeri, spine, and the soft tissue adjacent to the
      bone. The ratios of bone to soft tissue were calculated and compared to ratios
      drawn in a control group routinely referred for cardiac imaging and injected with
      (99m)Tc MIBI, after confirming the absence of any bone disease. The visual
      interpretation of the scans showed 48 patients to have increased bone uptake.
      Quantitative assessment showed significant difference between the mean ratios of
      the case and control groups. The Kruskal-Wallis test showed significant agreement
      between visual and quantitative ratios drawn from delayed right and left femora
      and left humerus images (P < 0.05). (99m)Tc MIBI whole body imaging is a
      potentially useful technique for assessing metabolic bone disease associated with
      hyperparathyroidism. Quantitative analysis helped in confirming the visual
      findings. 

PMID- 23961250
TI  - Optimal timing of bisphosphonate administration in combination with samarium-153
      oxabifore in the treatment of painful metastatic bone disease.
AB  - While bisphosphonates are indicated for prevention of skeletal-related events,
      radionuclide therapy is widely used for treatment of painful bone metastases.
      Combined radionuclide therapy with bisphosphonates has demonstrated improved
      effectiveness in achieving bone pain palliation in comparison to mono therapy
      with radionuclides or bisphosphonates alone. However, there are conflicting
      reports as to whether bisphosphonates adversely influence skeletal uptake of the
      bone-seeking radiotracers used for therapy. Recent studies analyzing influence of
      Zoledronic acid on total bone uptake of Samarium-153 EDTMP (Sm-153 EDTMP) by
      measuring cumulative urinary activity of Sm-153 on baseline study, as well as in
      combination with bisphosphonates (administrated 48 hours prior to Sm-153) did not
      provide any statistically significant difference in urinary excretion of Sm-153
      between the two groups. It may be noted that the exact temporal sequence of
      bisphosphonate administration vis a vis radionuclide therapy has not yet been
      studied. One of the side effects of bisphosphonates is transient flare effect on
      bone pain. Radionuclide therapy may also have similar side effect. Keeping in
      view the above the current study was designed with the main objective of
      determining the exact timing of bisphosphonate administration in patients
      receiving combined therapy so as to achieve optimal efficacy of bone pain
      palliation. Ninety-three patients suffering from metastatic bone pain who
      received combination therapy with Sm-153 oxabifore (an analog of Sm-153 EDTMP)
      and Zoledronic acid were divided into three groups according to the timing of
      Zoledronic acid administration: Group I: 39 patients who received Zoledronic acid
      7 or more days prior to Sm-153 oxabifore treatment; Group II: 32 patients who
      received Zoledronic acid 48-72 hours prior to Sm-153 oxabifore treatment and
      Group III: 22 patients who received Zoledronic acid 7 days after Sm-153 oxabifore
      treatment. Sm-153 oxabifore was administered to all patients at the standard bone
      palliation dose of 37 MBq/kg body weight. All patients received Zoledronic acid
      before and after treatment in standard dosage of 4 mg every 28 days. WB bone
      scan, CT, and MRI were performed before treatment in all patients to exclude cord
      compression and vertebral fractures. Pain scores and quality of life (QOL)
      measurements were recorded meticulously in all patients. In groups I, II, and
      III, pain relief occurred in 10.4 +/- 3.1 (Range = 5-15); 3.1 +/- 1.1 (Range = 1
      5) and 22 +/- 5.1 (Range = 15-35) days, respectively, following radionuclide
      therapy. There was statistically significant difference between pain score in all
      groups before and after treatment as well as statistically significant difference
      in time to pain relief onset between Group II and other groups of patients (P <
      0.0001). Based on our results we concluded that administration of Zoledronic acid
      48-72 hours prior to Sm-153 oxabifore treatment helps in achieving better pain
      relief, as well as at the shortest time interval from the start of therapy. 

PMID- 23961251
TI  - Effectiveness of bone metastases treatment by sm-153 oxabifore in combination
      with monoclonal antibody denosumab (xgeva): first experience.
AB  - Breast and prostate cancer have a propensity to metastasize to bones and cause
      osteolysis and abnormal new bone formation. Metastases locally disrupt normal
      bone remodeling. Although metastases from prostate cancer have been classified as
      osteoblastic based on the radiographic appearance of the lesion, data gleaned
      from a rapid autopsy program indicate that the same prostate cancer patient may
      have evidence of both osteolytic and osteoblastic disease as shown by histologic
      examinations. Thus, bone metastases are heterogeneous, requiring combined
      treatment targeting on both osteolytic and osteoblastic lesions. While Samarium
      153 (Sm-153) oxabifore treatment is widely used for the relief of pain in
      patients with osteoblastic metastatic bone lesions, Xgeva (Denosumab) is
      indicated for the prevention of skeletal-related events in patients with bone
      metastases from solid tumors. It is a fully human monoclonal antibody that has
      been designed to target receptor activator of nuclear factor-kB ligand (RANKL), a
      protein that acts as the primary signal to promote bone removal. In many bone
      loss conditions, RANKL overwhelms the body's natural defense against bone
      destruction. The main objectives of the current pilot study were to estimate the
      effectiveness of bone metastases treatment by a combination of Sm-153 oxabifore
      and Xgeva (Denosumab). Five patients (four female and one male, aged 35-64, mean
      age 50.8) with multiple skeletal metastases from prostatic carcinoma (1) and
      breast carcinoma (4) were studied. Their mean objective pain score according to
      visual analog scoring system on a 1-10 scoring system was 7.8 +/- 0.5 (range 6
      9). Sm-153 oxabifore was administered at the standard bone palliation dose of 37
      MBq/kg body weight. Xgeva (Denosumab) was administered at a dosage of 120 mg
      every 4 weeks, with the monitoring of calcium level and administration of
      calcium, magnesium, and vitamin D. Whole body (WB) bone scan was performed before
      and 3 months after treatment in all patients. After Sm-153 oxabifore
      administration, pain relief occurred within 4.4 +/- 1.25 days (range 2-9 days)
      and the objective pain score decreased to 0.2 +/- 0.2 (range 0-1). There was
      statistically significant difference found, according to the pain score system,
      before and after treatment (P < 0.0001). WB bone scan showed that in one patient,
      there was significant reduction in the number and intensity of bone metastases,
      and in four patients, there was no evidence of bone metastases found. Based on
      our first experience, combined treatment of bone metastases with Sm-153 oxabifore
      and Denosumab is effective and safe. 

PMID- 23961252
TI  - Development of nanoradiopharmaceuticals by labeling polymer nanoparticles with tc
      99m.
AB  - Nanomedicine is considered as the future of modern medicine. Hence, serious
      global efforts are being made for the development of nanopharmaceuticals. Among
      all the nanopharmaceuticals developed so far, radiopharmaceuticals constitute
      only a very small portion, as noted in the published literature. The procedures
      for development of nanoradiopharmaceuticals are complex. In this paper we discuss
      the results of a research directed at developing nanoradiopharmaceuticals based
      on three different types of nanopharmaceuticals as alternative drug delivery
      systems. 

PMID- 23961253
TI  - Labeling and Biological Evaluation of (99m)Tc-HYNIC-Trastuzumab as a Potential
      Radiopharmaceutical for In Vivo Evaluation of HER2 Expression in Breast Cancer.
AB  - The amplification of HER2 gene has been described in several tumor types, mainly
      breast cancer with a subsequent increase in HER2 protein expression. Trastuzumab
      is a humanized monoclonal antibody that recognizes selectively the HER2
      extracellular domain. The objective of the present work was to standardize the
      conjugation of Trastuzumab with Succinimidyl-hydrazinonicotinamide (HYNIC) and
      labeling with (99m)Tc to obtain (99m)Tc-HYNIC-Trastuzumab for use as in vivo
      tracer of the HER2 expression in breast cancer. The labeling procedure involved
      derivatization of 0.067 MUmol of Trastuzumab with 0.33 MUmols of HYNIC in
      dimethyl sulfoxide (DMSO). The mixture was incubated for 30 min. A mixture of
      Tricine and SnCl2.2H2O was prepared by add a solution of 44.6 MUmols Tricine in
      0.05 mL HCl 2.0 M and a similar volume of another solution containing 44.3 MUmols
      SnCl2.2H2O in 0.5 mL HCl 2.0 M. Then, 0.05 mL of this mixed was added to the
      conjugated with 296 MBq of 99mTcO-4. The final mixture was incubated at room
      temperature (18-25 degrees C) for 30 min. Radiochemical purity of the labeled
      solution was studied by chromatography, to evaluate (99m)Tc-Tricine,
      (99m)TcO2.H2O, and free (99m)TcO4 (-). Radiochemical purity was also evaluated by
      HPLC. Stability studies were tested in solution at 4 degrees C and lyophilized at
      4 degrees C. Biodistribution studies were performed in healthy CD-1 female mice
      at 2, 5, and 24 h (n = 3) and CD-1 female mice spontaneous breast adenocarcinoma
      (n = 3). Scintigraphic images of spontaneous breast adenocarcinoma in female CD-1
      mice were acquired in a gamma camera at 2, 5, and 24 h post-injection. Labeling
      was easily performed with high yields (>90%) and radiopharmaceutical stability
      for 24 h post-labeling. Stability studies revealed that antibody derivative must
      be lyophilized for undamaged storage. Biodistribution studies and imaging
      revealed excellent uptake in the tumor. Based on the results it was concluded
      that (99m)Tc-HYNIC-Trastuzumab could be a promising radiopharmaceutical for in
      vivo diagnosis of the HER2 status in breast with impact on treatment planning. 

PMID- 23961254
TI  - Potential requirement of positron emission tomography apparatuses in Asia and
      latin america including Mexico.
AB  - The number of positron emission tomography (PET) machines has been increasing in
      regions of East-, Southeast-, and South-Asia as well as in Latin America
      including Mexico. This study was performed to assess the potential requirement of
      PET machines in 19 countries which already use PET in the aforementioned regions.
      Data on the number of PET machines and internationally available characteristics
      of the restrictive countries such as the land area, the total population, the
      gross national income (GNI), and the average life span of inhabitants were
      obtained from IAEA, UN, WB, and WHO. Correlation between the number of PET
      machines and the characteristics of each country was evaluated. The potentially
      required number of PET machines, which was obtained by adjusting the number of
      PET machines with statistically significant, correlative characteristics of each
      country, standardized on the state of Japan, were compared. The number of PET
      machines could be significantly correlated to the GNI of a country and the
      average life span of its inhabitants (P < 0.05). Based on Japan, most of the
      countries in the regions would require considerably more PET machines. With
      installation of the potentially required number of PET machines in each of the
      countries, the number of PET machine per 10(6) population would increase by 1.1-
      to 12-fold, in comparison with the current situation. With regards to the
      potentially required number of PET machines, most of the countries in these
      regions may require a considerable increase of PET machines. Nevertheless, some
      countries in the Asia seem to require outside assistance such as international
      support in order to introduce PET and enhance the efficacy of their health
      services. 

PMID- 23961255
TI  - Focal FDG Uptake in Lung Parenchyma Without Structural Alterations on CT.
AB  - Transient visualization of a FDG avid abnormality in the lungs without any
      structural lesion is reported in a case of iatrogenic pulmonary microembolism. 

PMID- 23961256
TI  - A rare case of suprahepatic gall bladder with phocomelia and pancytopenia:
      detected by tc-99m mebrofenin scintigraphy.
AB  - The possibility of an ectopic gallbladder should always be considered whenever
      there is a failure to localize it in its normal anatomical position on routine
      imaging. Although a very rare entity, the anomalous position of gallbladder can
      result in misinterpretation of imaging findings and create clinical confusion.
      Awareness of such an anomaly facilitates proper diagnosis and subsequent
      management. The authors report a very rare case of suprahepatic gallbladder
      associated with phocomelia, pancytopenia, and splenomegaly in a young 25-year-old
      female. The suprahepatic gallbladder was initially visualized on Technetium-99m
      (Tc-99m) Mebrofenin radionuclide hepatobiliary scintigraphy. Subsequent magnetic
      resonance cholecystopancreatography (MRCP) was also done to confirm the
      diagnosis. 

PMID- 23961257
TI  - (18)F-FDG PET-CT for Staging of Conjunctival Melanoma.
AB  - The value of F-18 fluorodeoxyglucose positron emission tomography/computed
      tomography ((18)F-FDG PET-CT) for the evaluation of cutaneous melanoma has been
      demonstrated previously. However, there are few reports regarding the use PET-CT
      for the staging of conjunctival melanoma (CM). We report here a case, a 34-year
      old male with a six-month history of a pigmented nodule at the palpebral
      conjunctiva of the left eye, and a firm left preauricular lymph node detected on
      physical examination. Biopsy of the ocular lesion confirmed CM, and fine needle
      aspiration cytology of the preauricular node was positive for malignancy. CT
      showed three pulmonary nodules. An (18)F-FDG PET-CT was performed to restage the
      patient. The study showed hypermetabolic lesions in the left eye, and in the left
      preauricular node. The scan was negative for metastasis. These findings were
      important in guiding management of the disease in this patient. Future
      prospective studies should further evaluate the role of (18)F-FDG PET-CT for the
      staging of CM. 

PMID- 23961258
TI  - Excessive Hepatic Arterial-portal Venous Shunting May Predict Failure of
      Microparticle Localization in Hepatocellular Carcinomas.
AB  - Locoregional treatment of hepatocellular carcinomas using yttrium-90 (Y-90)
      microspheres is an emerging modality, and involves the administration of such
      radioactive particles directly into the hepatic arterial vasculature. We present
      the case of a 58-year-old gentleman undergoing evaluation for Y-90 microsphere
      therapy for hepatocellular carcinoma, in which our findings suggest that
      significant hepatic arterial portal venous shunting detected during the angiogram
      maybe a predictor of poor localization of microspheres in the turmor, and that
      centers that utilize body surface area (BSA) approaches for dosimetry should take
      note of such findings. 

PMID- 23961259
TI  - Epidermal growth factor receptor mutation in lung adenocarcinoma in India: A
      single center study.
AB  - BACKGROUND: Adenocarcinoma, a subgroup of non-small cell lung cancer, is the most
      frequent form occurring in the non-smokers. Mutation in tyrosine kinase domain of
      epidermal growth factor receptor (EGFR) has been a common feature observed in
      lung adenocarcinoma. The study was carried out to detect the prevalence of EGFR
      mutation in lung adenocarcinoma. MATERIALS AND METHODS: EGFR mutation status in
      166 lung adenocarcinoma patients was obtained retrospectively. Mutation tests
      were performed on paraffin embedded tissue blocks as a routine diagnostic
      procedure by polymerase chain reaction followed by direct nucleotide sequencing.
      Patient's demographics and other clinical details were obtained from the medical
      records. RESULTS: EGFR mutation was detected in 43/166 (25.9%) patients. Gender
      wise mutation was observed as 18/55 (32.7%) in females and 25/111 (22.5%) in
      males. Overall, EGFR mutation was correlated with never smokers and distant
      metastasis (P < 0.05), but not associated with the gender, disease stage and
      pleural effusion. Exon 19 deletions were significantly correlated with females,
      never smokers, pleural effusion and distant metastasis (P < 0.05). However, point
      mutation on exon 21 did not show any statistical association with the above
      variables. Median overall survival was 22 months (95% confidence interval, 15.4
      28.6). Female sex, EGFR mutation and absence of metastasis are associated with
      good prognosis. CONCLUSION: EGFR mutation in lung adenocarcinoma was higher in
      never smokers, females and patients with distant metastasis. However, it was not
      linked with tobacco smoking. The prevalence of EGFR mutation observed is in range
      with the previously published reports from the Asian countries.

PMID- 23961260
TI  - Mapping cancer cell metabolism with(13)C flux analysis: Recent progress and
      future challenges.
AB  - The reprogramming of energy metabolism is emerging as an important molecular
      hallmark of cancer cells. Recent discoveries linking specific metabolic
      alterations to cancer development have strengthened the idea that altered
      metabolism is more than a side effect of malignant transformation, but may in
      fact be a functional driver of tumor growth and progression in some cancers. As a
      result, dysregulated metabolic pathways have become attractive targets for cancer
      therapeutics. This review highlights the application of(13)C metabolic flux
      analysis (MFA) to map the flow of carbon through intracellular biochemical
      pathways of cancer cells. We summarize several recent applications of MFA that
      have identified novel biosynthetic pathways involved in cancer cell proliferation
      and shed light on the role of specific oncogenes in regulating these pathways.
      Through such studies, it has become apparent that the metabolic phenotypes of
      cancer cells are not as homogeneous as once thought, but instead depend strongly
      on the molecular alterations and environmental factors at play in each case. 

PMID- 23961261
TI  - Cancer metabolism meets systems biology: Pyruvate kinase isoform PKM2 is a
      metabolic master regulator.
AB  - Pyruvate kinase activity is controlled by a tightly woven regulatory network. The
      oncofetal isoform of pyruvate kinase (PKM2) is a master regulator of cancer
      metabolism. PKM2 engages in parallel, feed-forward, positive and negative
      feedback control contributing to cancer progression. Besides its metabolic role,
      non-metabolic functions of PKM2 as protein kinase and transcriptional coactivator
      for c-MYC and hypoxia-inducible factor 1-alpha are essential for epidermal growth
      factor receptor activation-induced tumorigenesis. These biochemical activities
      are controlled by a shift in the oligomeric state of PKM2 that includes
      acetylation, oxidation, phosphorylation, prolyl hydroxylation and sumoylation.
      Metabolically active PKM2 tetramer is allosterically regulated and responds to
      nutritional and stress signals. Metabolically inactive PKM2 dimer is imported
      into the nucleus and can function as protein kinase stimulating transcription. A
      systems biology approach to PKM2 at the genome, transcriptome, proteome,
      metabolome and fluxome level reveals how differences in biomolecular structure
      translate into a global rewiring of cancer metabolism. Cancer systems biology
      takes us beyond the Warburg effect, opening unprecedented therapeutic
      opportunities. 

PMID- 23961262
TI  - Restoration of the methylation status of hypermethylated gene promoters by
      microRNA-29b in human breast cancer: A novel epigenetic therapeutic approach.
AB  - It is well established that transcriptional silencing of critical tumor
      suppressor genes by DNA methylation is a fundamental component in the initiation
      of breast cancer. However, the involvement of microRNAs (miRNAs) in restoring
      abnormal DNA methylation patterns in breast cancer is not well understood.
      Therefore, we investigated whether miRNA-29b, due to its complimentarity to the
      3'- untranslated region of DNA methyltransferase 3A (DNMT3A) and DNMT3B, could
      restore normal DNA methylation patterns in human breast cancers and breast cancer
      cell lines. We demonstrated that transfection of pre-miRNA-29b into less
      aggressive MCF-7 cells, but not MDA-MB-231 mesenchymal cells, inhibited cell
      proliferation, decreased DNMT3A and DNMT3B messenger RNA (mRNA), and decreased
      promoter methylation status of ADAM23 , CCNA1, CCND2, CDH1, CDKN1C, CDKN2A, HIC1,
      RASSF1, SLIT2, TNFRSF10D, and TP73 tumor-suppressor genes. Using methylation
      polymerase chain reaction (PCR) arrays and real-time PCR, we also demonstrated
      that the methylation status of several critical tumor-suppressor genes increased
      as stage of breast disease increased, while miRNA-29b mRNA levels were
      significantly decreased in breast cancers versus normal breast. This increase in
      methylation status was accompanied by an increase in DNMT1 and DNMT3B mRNA in
      advanced stage of human breast cancers and in MCF-7, MDA-MB-361, HCC70, Hs-578T,
      and MDA-MB-231 breast cancer cells as compared to normal breast specimens and MCF
      10-2A, a non-tumorigenic breast cell line, respectively. Our findings highlight
      the potential for a new epigenetic approach in improving breast cancer therapy by
      targeting DNMT3A and DNMT3B through miRNA-29b in non-invasive epithelial breast
      cancer cells. 

PMID- 23961263
TI  - Letter from the editor.

PMID- 23961266
TI  - Advanced endoscopic training.

PMID- 23961264
TI  - Postinfectious functional gastrointestinal disorders: a focus on epidemiology and
      research agendas.
AB  - Epidemiologic research is fundamental and complementary to our understanding of
      disease and development of primary, secondary, and tertiary interventions. To put
      the current evidence into context and identify gaps and research priorities in
      the areas of disease attribution, burden of disease, clinical characterization,
      and management of postinfectious functional gastrointestinal disorders (PI-FGDs),
      we took a multidisciplinary approach from the domains of infectious disease,
      gastroenterology, epidemiology, and public health. Our review of data from these
      disciplines found that, despite a complete understanding of pathoetiology,
      studies continue to accumulate and point toward evidence of a causal association
      for FGD. For some FGDs, Bradford Hill's criteria for causality yield more
      certainty than other criteria. In addition, the growing recognition of the impact
      of acute foodborne illness on economics and society is leading to exploration of
      the potential long-term health effects and disease burden of PI-FGDs, although a
      paucity of data exist in terms of pathogen-specific risk, disability duration,
      and relevant disability weights. Lastly, the understanding of PI-FGDs is changing
      the way research is approached and suggests a need for a more expansive
      exploration of biologic mechanisms and how FGDs are categorized. Areas of
      research priorities are catalogued in this paper and will hopefully provide
      inspiration for future studies and contributions to the field of
      gastroenterology. 

PMID- 23961267
TI  - Epidemiologic concerns and advances in knowledge on hepatitis E.

PMID- 23961265
TI  - Computed tomography colonography for colorectal cancer screening.
AB  - Colorectal cancer screening has been shown to help prevent cancer-related death.
      Concerns about suboptimal adherence to conventional colonoscopy has led to the
      search for alternative screening modalities. Computed tomography colono-graphy
      (CTC) is a highly sensitive and minimally invasive alternative modality. The
      American College of Radiology has established a standardized reporting system for
      CTC. The advantages of CTC include complete colonic examination and extraluminal
      imaging in a single breath hold time. Lack of sensitivity in the evaluation of
      flat lesions and radiation exposure are the main concerns with this modality.
      Although the usefulness of CTC has been demonstrated in academic centers, larger
      studies in community settings are needed to facilitate its adoption by healthcare
      services. 

PMID- 23961268
TI  - Prevention, detection, and treatment of osteopenia and osteoporosis.

PMID- 23961269
TI  - Management of bile reflux.

PMID- 23961270
TI  - Mucosal schwann cell hamartoma of the colon in a patient with ulcerative colitis.

PMID- 23961271
TI  - Mucosal schwann cell hamartoma in ulcerative colitis: diagnosis and clinical
      relevance.

PMID- 23961272
TI  - Psychosocial and Behavioral Issues in Children and Adolescents with IBD: Clinical
      Implications.

PMID- 23961273
TI  - An unusual cause of abdominal pain: duodenal cystic lymphangioma.

PMID- 23961274
TI  - Toward an understanding of lymphatic malformations.

PMID- 23961275
TI  - Enalapril protects endothelial cells against induced apoptosis in Alzheimer's
      disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease
      in which endothelial cell (EC) can be affected. In brain, functional changes in
      ECs contribute to reductions in resting blood flow. Furthermore, angiotensin
      converting enzyme inhibitors (ACE-I) have beneficial effects on endothelial
      dysfunction. This is the first study that presents direct experimental evidence
      associating endothelial apoptosis as a basis of AD pathogenesis and response to
      an ACE-I therapy. MATERIALS AND METHODS: Human umbilical vein ECs (HUVECs) were
      treated with sera from AD patients and sera from healthy volunteers (each group,
      n = 10). Apoptosis was determined by annexin V-propidium iodide staining and cell
      death detection kit. The effect of 50 MUM enalapril on endothelial apoptosis was
      assessed. Nitrite (NO2 (-)) levels were determined in the culture supernatants.
      RESULTS: Enalapril suppressed the induction of apoptosis by the serum of patients
      only when used before treating HUVECs with the sera of AD. Mean +/- SD of
      apoptosis induction in the control group was 6.7 +/- 3.69; in the group treated
      with sera of AD for 24 h was 47.78 +/- 0.65; in the group wherein sera from AD
      was added (pretreatment) after exposure of HUVECs by 50 MUM enalapril for 24 h
      was 26.6 +/- 2.63; and in the group wherein HUVECs were exposed in the sera of AD
      for 24 h and then 50 MUM enalapril was added to these cells for another 24 h
      (post-treatment) was 56.87 +/- 5.51. Also, the mean +/- SD of NO2 (-)
      concentration showed significantly greater levels of dissolved NO2/NO3 metabolite
      in the culture media of untreated HUVECs by enalapril (1.03 +/- 0.06) as compared
      with control (0.26 +/- 0.13; P < 0.05), while the rate of nitric oxide (NO)
      significantly decreased when enalapril was presented in culture both in the
      pretreatment (0.07 +/- 0.003) and in the post-treatment group (0.06 +/- 0.005; P
      < 0.05). CONCLUSION: It could be concluded that EC treated with sera from AD
      patients activates apoptosis in HUVECs; this effect was reversed by enalapril
      pretreatment. This can be proposed as a therapeutic approach for Alzheimer's
      patients.

PMID- 23961276
TI  - Thr698Thr (nt2369) polymorphism on CACNA1A gene and head pain severity in
      familial migraine.
AB  - BACKGROUND: Migraine is a common neurological disorder with a significant genetic
      component. Less information is known about the contribution of minor genetic
      variations, such as single nucleotide polymorphism (SNP) on the migraine process.
      In the present study, we aim to investigate the role of CACNA1A gene polymorphism
      on severity and related factors in family positive migraine patients. MATERIALS
      AND METHODS: We included 74 common migraine patients consequently. Headache
      severity was evaluated according to Headache Impact Test (HIT6) questionnaire and
      quality of life of patients was investigated according to MSQ (Migraine-Specific
      Quality of Life Questionnaire v2.1) questionnaire. Thirty patients with positive
      family history of migraine were selected and sequencing analysis after DNA
      extraction was performed. RESULTS: Direct sequencing revealed a known SNP G to A
      transition in the exon 16 (nt2369, G -> A) in 9 patients. There was no
      significantly correlation between polymorphism and type of migraine, severity,
      frequency, duration and quality of life in family positive migraine. Evaluated
      migraine severity by HIT6 questioner couldn't act as a risk factor for this
      polymorphism (OR: 0.93, CI%95 0.82-1.06 P = 0.3). CONCLUSION: In Iranian
      population no significant association was seen between Thr698Thr (nt2369)
      polymorphism and head pain severity in familial migraine. Confirmation of this
      hypothesis needs further investigation.

PMID- 23961277
TI  - Malnutrition is associated with depression in rural elderly population.
AB  - BACKGROUND: Aging induces physiological changes and affects all of organs.
      Nutritional status and mental health deteriorate with aging. As malnutrition and
      depression are main problem in elderly this study was performed to assess the
      association between malnutrition and depression among rural elderly. MATERIALS
      AND METHODS: Three hundred and seventy rural elderly aged over 60 years were
      examined in a cross-sectional study by systematic sampling method and using mini
      nutritional assessment (MNA), which is a standard questionnaire for evaluating
      nutrition status. Depression was evaluated by a validated questionnaire in the
      elderly. Correlation between Socio-demographic characteristic, diseases, and
      nutrition status was obtained by t-test, Chi-square test and logistic regression
      in elderly population. RESULTS: Mean +/- SD age was 70.6 +/- 7.3 years. Frequency
      of malnutrition was similar in both genders. According to MNA, 3.8% of subjects
      suffered from malnutrition, 32.7% were at risk of malnutrition and 63.5% were
      well-nourished. Nutrition status correlated with body mass index (P = 0.028) and
      depression (P = 0.001). The risk of severe depression in patients with
      malnutrition was 15.5 times higher than non-depressed persons (odd ratio: 15.5;
      95% CI: 2.9-82.5). CONCLUSION: Depression could act as a powerful risk for
      malnutrition in elderly population that it should be controlled by physicians.

PMID- 23961278
TI  - Evaluation of neural gene expression in serum treated embryonic stem cells in
      Alzheimer's patients.
AB  - BACKGROUND: Previous studies confirmed that neural gene expression in embryonic
      stem cells (ESC) could influence by chemical compounds through stimulating
      apoptotic pathway. We aimed to use ESCs-derived neural cells by embryoid body
      formation as an in vitro model for determination of neural gene expression
      changes in groups that treated by sera from Alzheimer's patients and compare with
      healthy individuals. MATERIALS AND METHODS: ESC line which was derived from the
      C57BL/6 mouse strain was used throughout this study. ESC-derived neural cells
      were treated with serum from Alzheimer's patient and healthy individual. Neural
      gene expression was assessed in both groups by quantitative real-time polymerase
      chain reaction analysis. The data was analyzed by SPSS Software (version 18).
      RESULTS: Morphologically, the reducing in neurite out-growth was observed in
      neural cells in group, which treated by serum from Alzheimer's patient, while
      neurite growth was natural in appearance in control group. Microtubule-associated
      protein 2 and glial fibrillary acidic protein expression significantly reduced in
      the Alzheimer's patient group compared with the control group. Nestin expression
      did not significantly differ among the groups. CONCLUSION: Neural gene expression
      could be reduced in serum treated ESC in Alzheimer's patients.

PMID- 23961279
TI  - Prevalence and clinical characteristics of headache among medical students,
      Isfahan, Iran.
AB  - BACKGROUND: Headache is one of the most common complaints during medical
      curriculum and it occurs due to numerous psychological and physical stressors,
      which are more common in medical students than general population. The purpose of
      this study was to evaluate the frequency of different types of headache and
      associated factors. MATERIALS AND METHODS: This cross-sectional study was
      conducted in Isfahan University of Medical Sciences, from September 2011 to
      January 2012. First- to seven-year medical students who have experienced some
      forms of headache in their life and had headache attacks during the past 6 months
      were included in this study. All medical students completed a structured check
      list, which consisted of demographics data, associated factors, and headache
      characteristics. RESULTS: A total of 480 (258 [53.8%] males and 222 [46.2%]
      females) students (93.7%) were evaluated. The prevalence of headache was 58.7%,
      the prevalence of migraine, and tension-type headache was 14.2% (10.5% in male
      vs. 18.5% in female, P = 0.08) and 44.2% (49.2% in male vs. 39.2% in female, P =
      0.006), respectively. A family positive history was found in 9.5% of students
      with headache. The lower socio-economic status, year of study (3(rd) and 5(th)
      year students), was seemed to had higher prevalence in students with headache.
      There was no significant difference between headache and concomitant disease.
      CONCLUSION: The results demonstrate that prevalence of headache is high among
      medical student. Socio-economic and the year of study might be significant
      factors in the prevalence of headache. Further multicenter studies would be
      necessary to evaluate headache epidemiology among medical students in the whole
      country.

PMID- 23961280
TI  - Transcranial sonography on Parkinson's disease and essential tremor.
AB  - BACKGROUND: The study on transcranial sonocraphy (TCS) as a diagnostic test for
      Parkinson's disease (PD) has been neglected in some hospitals. The current study
      was conducted as the first study to investigate the utility of TCS for diagnosis
      of PD and its ability to distinguish PD from essential tremor (ET) in an Iranian
      population. MATERIALS AND METHODS: TCS of substantia nigra (SN) was performed on
      50 PD, 48 ET, and 50 healthy controls by two blinded investigators. RESULTS:
      Bilateral SN margin over 0.20 cm(2) was found in 39 (90%) and 7 (15%) in PD and
      ET patients, respectively. Furthermore, 4 (8%) of healthy control displayed this
      particular echo feature as well (false positives). SN hyperechogenicity >=0.20
      cm(2) was considered as a cut-off point to detected PD. Accordingly, TCS proved
      90% (95% confidence interval [CI]: 77.85-97.35) sensitive and 92% (95% CI: 80.75
      97.73)specific for the detection of PD by visualizing the SN. CONCLUSION: SN
      hyperechogenicity >=20 cm(2) is a specific feature of PD. Since, the symptoms of
      PD and ET might be overlapping; this method seems to be reliable to confirm PD
      diagnosis in doubtful clinical cases. Further studies in years to come are
      warranted to shed light on standardized data for Iranian to enhance the validity
      of TCS.

PMID- 23961281
TI  - Electrocardiographic changes in patients with refractory epilepsy.
AB  - BACKGROUND: Epilepsy is the second most common type of chronic neurological
      disease. Its diagnosis carries an excess mortality, which is 2-3 times higher
      than that of general population. Mortality rates are increased among patients
      with uncontrolled seizures. The aim of this study was to characterize the
      electrocardiogram (ECG) changes during pre-ictal, ictal and post-ictal states in
      pharmaco-resistant epilepsy patients. MATERIALS AND METHODS: This retrospective
      study conducted by Department of Neurology and Department of Cardiology of
      Isfahan Medical University from September 2008 to December 2012, patients with
      medically refractory epilepsy who underwent standard pre-surgical assessment from
      Epilepsy ward of Kashani hospital in Isfahan city were recruited in this study.
      RESULTS: The heart rate (HR) varied significantly throughout the record.
      Significant difference in HR was identified between ictal and pre-ictal periods
      (P = 0.000), furthermore, the difference between ictal and pre-ictal HR {mean =
      63.867 +/- 0.061, P = 0.000}, ictal and post-ictal HR {mean = 38.833 +/- 0.067, P
      = 0.003}, and between pre- and post-ictal HR {mean = 25.033 +/- 0.089, P =
      0.000}, was significant. CONCLUSION: ECG monitoring should be a part video-
      (electroencephalography) EEG monitoring to identify serious cardiac
      abnormalities, particularly in patients with refractory epilepsy.

PMID- 23961282
TI  - The value of provocative tests in diagnosis of cervical radiculopathy.
AB  - BACKGROUND: This study was aimed at assessing the accuracy of provocative tests
      in diagnosis of acute or chronic Cervical Radiculopathy (CR) based on an
      electrodiagnostic reference criterion. MATERIALS AND METHODS: Shoulder Abduction
      Test (SAT), Spurling Test (ST), Upper Limb Tension Test (ULTT), and
      electromyography were done on 97 patients who referred to Electrodiagnostic
      center in the university hospital from January 2010 to March 2011. All of the
      participants had neck and radicular pain for at least 3 weeks. They were
      classified according to electrodiagnostic findings. Then diagnostic values of
      provocative tests were assessed in diagnosis of acute or chronic CR on the basis
      of reference criterion. RESULTS: SAT and ST were more specific (85%) compared to
      ULTT, while ULTT was more sensitive (60.46% in acute and 35.29% in chronic) than
      the other two. SAT and ST had a significant accuracy for comparison between acute
      and chronic CR (P < 0.05). CONCLUSION: ULTT is suitable for screening of CR,
      while SAT and ST can support diagnosis. SAT and ST are good diagnostic tests for
      comparison between acute and chronic CR.

PMID- 23961283
TI  - Association between serum biochemical levels, related to bone metabolism and
      Parkinson's disease.
AB  - BACKGROUND: Vitamin D insufficiency and serum calcium disturbance have been
      reported to be more common in Parkinson's disease (PD) patients than in healthy
      control subjects, which may be due to a chronic disease or reduced mobility
      contributes to these relatively disturbances. Because of the high-vitamin D
      insufficiency in our population, we aimed to compare a biochemical levels which
      are related to bone metabolism, in PD patients in comparison with age-matched
      healthy controls, for the 1(st) time in a Middle East population. MATERIALS AND
      METHODS: This case-control study was involved 105 (20 were excluded) PD patients,
      who were age- and -sex matched with 112 controls. 25-hydroxyvitamin D (25OHD) and
      parathyroid hormone analyzed by enzyme immunoassay; another laboratory data
      including, calcium, phosphorous, and alkaline phosphatase were performed by
      spectrophotometric methods. RESULTS: There was no significant difference in 25OHD
      between PD patients and control group (P = 0.071). 25OHD level was not
      significantly different in PD patients compared to controls {odds ratio 1.003,
      (confidence interval [CI], 0.98-1.02), P value 0.793}. None of the other
      biochemical levels did not induce more chance for PD, only we observed in men has
      more risk of PD than women (odds ratio 2.53, [CI, 1.27-5.03], P value 0.008).
      CONCLUSION: Our data do not support a possible role of vitamin D insufficiency in
      PD. Regarding to variable changes in biochemical markers in PD patients than in
      controls; further studies are suggested to determine any plausibility role of
      them as a causal relationship or as an outcome of PD.

PMID- 23961284
TI  - Oral prednisolone in the treatment of cervical radiculopathy: A randomized
      placebo controlled trial.
AB  - BACKGROUND: Steroids are commonly used in the treatment of cervical radiculopathy
      (CR), but there is limited information in this regard. We evaluated the efficacy
      of oral prednisone in the treatment of CR. MATERIALS AND METHODS: This
      randomized, double-blinded, placebo-controlled trial was conducted on adult
      patients with neck/shoulder pain for at least 1 month with no alarm
      symptoms/sings of malignancy, infection, or severe myelopathy, and no
      contraindication for corticosteroid use. Patients were allocated to receive
      prednisolone 50 mg/day for 5 days that was tapered within the following 5 days,
      or placebo. All patients also received acetaminophen 325 mg three times a day and
      ranitidine 150 mg two times a day. Neck disability index (NDI) and the verbal
      rating scale (VRS) were used to evaluate the outcomes. RESULTS: A total of 59
      patients (31 female, mean +/- SD age = 46.2 +/- 9.0 years) completed the study. A
      significant decrease was observed regarding the NDI and VAS scores from baseline
      to the end of study in both groups (P < 0.001). However, for both the NDI (35.7
      +/- 21.4 vs. 12.9 +/- 10.2) and VRS (4.4 +/- 2.7 vs. 1.6 +/- 1.2), the amount of
      decrease was greater in the prednisone compared with the placebo group (P <
      0.001). Based on the clinically important change in NDI, pain was improved in
      75.8% (22/29) of the prednisolone and 30% (9/30) of the placebo group (P <
      0.001). CONCLUSION: A short course of oral steroid therapy with prednisolone is
      highly effective in reducing pain in patients referring with uncomplicated CR.
      Further studies are warranted on dosing, duration, and long-term efficacy and
      safety of oral steroid therapy, compared with injection approach.

PMID- 23961285
TI  - Evaluation of vasomotor reactivity in systemic lupus erythematosus patients and
      its comparison with the control group.
AB  - BACKGROUND: Neuropsychiatric abnormalities are among the most common
      manifestations of systemic lupus erythematosus (SLE). They have been proposed to
      be associated with impaired cerebral blood flow (CBF). Cerebral vasomotor
      reactivity (VMR) is a hemodynamic parameter effective in the autoregulation of
      CBF. The aim of the present study is to determine and compare the VMR of women
      with stable SLE and normal women. MATERIALS AND METHODS: According to the study
      criteria 60 women in each group entered the study. VMR was evaluated with
      Transcranial Doppler (TCD) at rest and after one minute of breath holding.
      RESULTS: There was no significant difference in the mean of age between two
      groups (31.76 +/- 7.50 years in the SLE group versus 32.43 +/- 4.55 years in the
      control group, P value: 0.64). The mean duration of SLE in the case group was
      5.40 +/- 3.60 years. The means of the Breath-Holding Index (BHI) in the SLE and
      control groups were 0.842 +/- 0.72% and 0.815 +/- 0.26%, respectively, which was
      not significantly different (P value: 0.82). CONCLUSION: This study indicates
      that the VMR of women with stable SLE is not significantly different from the age
      and sex-matched normal population. However, further investigations on patients
      with longer SLE duration and more neuropsychological abnormality rates are
      suggested.

PMID- 23961286
TI  - Protein consumptions in stroke patients.
AB  - BACKGROUND: Stroke is one of the most common causes of disabilities and death all
      over the world. The mortality rate of stroke is predicted to be doubled by 2030
      in the Middle East countries. Nutrition is an effective strategy in prevention
      and management of stroke. This study assessed the relationship between various
      protein types and stroke risk. MATERIALS AND METHODS: This hospital-based case
      control study was performed in a University hospital. The data regarding
      consumption of usual food intake of 69 cases (46 men and 23 women) and 60
      controls (30 men and 30 women) was collected with a food frequency questionnaire
      (FFQ). The mean consumption of red and white meat and vegetable and processed
      proteins consumption were compared between two groups. RESULTS: The percent of
      total of daily protein intake were lower in patients with stroke in both sexes
      (25.92% vs 30.55% in men and 30.7% vs 31.14% in women). CONCLUSION: Lower protein
      consumption may be observed in patients with stroke patients in both sex.

PMID- 23961287
TI  - Dietary intake of minerals in the patients with stroke.
AB  - BACKGROUND: Experimental studies provide evidence of a relationship between
      stroke and mineral intake but this information in human are still limited and
      inconsistent. The purpose of this study was to investigate sodium, calcium and
      iron intake and stroke in Iranian patient and control population. MATERIALS AND
      METHODS: In a case-control study with 46 stroke men (aged 56 +/- 18 years) and
      stroke women (aged 52 +/- 7 years) and 60 healthy people, we investigated the
      sodium, calcium and iron intake inthe patients. RESULTS: After adjustment for
      age, sex and cardiovascular disease we found that a high sodium intake was
      associated with a statistically significant higher risk of stroke (P < 0/05). We
      saw a significant association between iron intakes in men (P < 0/05). And calcium
      was not significant associated with risk of stroke (P for trend >0/05).
      CONCLUSION: These findings in men and women suggest that a low sodium intake may
      play a role in primary prevention of stroke.

PMID- 23961288
TI  - Comparison of fat intake between patients with stroke and normal population.
AB  - BACKGROUND: Stroke happens when blood flow to parts of brain stops. Stroke is
      sometimes called "brain attack." Risk factor is something that increases the
      chance of getting a disease. Some risk factors for stroke cannot be changed, but
      some can be altered. The chance of stroke is higher in people who live an
      unhealthy lifestyle by: Being overweight as a result of over-eating, eating too
      much fat, smoking, etc., Therefore, we compared the fat intake between patients
      with stroke and normal population. MATERIALS AND METHODS: Sixty nine patients
      with stroke (46 men and 23 women) as cases and 60 subjects (30 men and 30 women)
      as controls during April 2009 and May 2010 from Alzzahra hospital, Isfahan, Iran
      were evaluated. Dietary intakes were collected using a food frequency
      questionnaire (FFQ) through their close relatives such as spouse, daughter or
      mother. Also, anthropometry measurements such as weight, height and waist
      extracted from their medical files, however, body mass index (BMI) and waist to
      hip ratio (WHR) were calculated. RESULT: The intake of saturated fatty acids
      (SFA) and monounsaturated fatty acids (MUFA) both in men and women with stroke
      were significantly higher than controls (P = 0.04 and P = 0.03 for men and P =
      0.05 and P = 0.02 for women, respectively). Also, the mean intake of hydrogenated
      fats, butter, cream, mayonnaise sauce and nuts were higher in men with stroke
      with respect in control group; while, women with stroke consumed more
      hydrogenated fats, vegetable oils, cream and mayonnaise sauce than controls.
      CONCLUSION: Increased fat intake was observed in patients with stroke compared
      with normal population.

PMID- 23961289
TI  - Mutation analysis of CACNA1A gene in Iranian migrainous and review literatures.
AB  - BACKGROUND: There are contrary results about the role of CACNA1A gene in the
      causation of common migraine in different populations. However, migraine may be
      genetically heterogeneous and more studies in different families and populations
      are required for a definite conclusion. The aim of this study was to surveyed
      leukocyte genomic DNA mutation of CACNA1A in Iranian migraine patients with [MA]
      and without aura [MO] who has family history of migraine and we performed a
      narrative review of all studies that evaluated CACNA1A gene, non-hemiplegic
      migraine [MA and MO] and FHM [familial hemiplegic migraine]. MATERIALS AND
      METHODS: The 30 patients with family history of migraine were selected for
      mutations analysis for CACNA1A gene by PCR method. For review, we searched
      MEDLINE-PUBMED, ISI, Scopus and Cochrane databases up to December 2012. RESULTS:
      Mutation analysis of the 4 exons of the CACNA1A gene in these patients revealed
      no mutations in this gene. Direct sequencing revealed a polymorphism previously
      reported G to A transition in the exon 16 [nt2369, G->A] in 9 patients. In
      review, the correlation of FHM loci [CACNA1A gene] with MA and MO has been showed
      in different population and only small population from Caucasians presented this
      correlation. CONCLUSION: CACNA1A is most likely not a major susceptibility gene
      for common migraine in Iranian maigrainous. It's essential to study more on
      larger series and covering all 47 exons of the CACNA1A gene to confirm this
      hypothesis.

PMID- 23961290
TI  - Cow's milk allergy in multiple sclerosis patients.
AB  - BACKGROUND: Exposure to some environmental agent such as different nutrition and
      contact with allergens may have a role in developing multiple sclerosis (MS). The
      present study was aimed to evaluate the cow's milk allergy (CMA) in MS patients
      compared to healthy controls. MATERIALS AND METHODS: Between March 2012 and July
      2012, 48 MS patients were selected and compared with 48 healthy subjectsto assess
      the frequency of CMA in MS patients compared to healthy control. Cow's milk
      specific immunoglobin E (IgE) was determined by Immuno CAP. Sex and the frequency
      of CMA were compared between study groups by Chi-square test. RESULTS: Total of
      96 subjects were assessed (22% male and 78% female). The mean age of the study
      subjects was 30.8 +/- 6.6 years. Mean age of case and control groups was 30.7 (+/
      6.9) versus 30.9 +/- 6.3, respectively (P value = 0.83). There were no detection
      of cow's milk specific IgE in serum of MS patients and healthy subjects.
      CONCLUSION: There was no difference between MS and healthy subjects regarding
      CMA.

PMID- 23961291
TI  - The relationship between serum levels of vitamin D and migraine.
AB  - BACKGROUND: Migraine is common worldwide. In recent years, vitamin D deficiency
      has been determined as a global health problem. A few studies have shown inverse
      relationship between serum vitamin D levels and headache. Thus, in this study, we
      assessed relationship between serum vitamin D levels with migraine. MATERIALS AND
      METHODS: The present study was a cross-sectional. Seventy-six migraine patients
      aged 10-61 years were included. The multiple linear regression was used to show
      association between serum 25-0H-D3 and migraine. Adjustments were performed for
      age, sex, waist circumference, body mass index (BMI), number of chronic diseases,
      and education level. RESULTS: The positive weak relationship was observed between
      serum vitamin D and headache diary result (P = 0.042, r = 0.19). But, no
      significant relationship was observed between serum vitamin D and migraine
      severity (P = 0.741). CONCLUSION: High levels of serum 25-OH-D3 was related to
      higher headache diary result. After adjustment for confounding variables, this
      significant association remained. No significant relationship was shown between
      serum vitamin D and migraine severity.

PMID- 23961292
TI  - Circadian rhythm sleep disorders in patients with multiple sclerosis and its
      association with fatigue: A case-control study.
AB  - BACKGROUND: Circadian rhythm sleep disorders are a presentation of sleep
      disorders in patients with multiple sclerosis (MS). This study aims to compare
      this problem in MS patients with healthy people and to determine its association
      with chronic fatigue in MS patients. MATERIALS AND METHODS: A case-control study
      was performed on 120 MS patients and 60 healthy subjects matched for age and sex,
      in 2009 in MS Clinic Alzahra Hospital. Sleep quality, rhythm and fatigue severity
      were assessed using PSQI (Pittsburgh sleep quality index) and FSS (Fatigue
      severity Scale) questionnaires, respectively. Its reliability and validity has
      been confirmed in several studies (Cronbach's alpha = 0.83). This index has seven
      sections including patient's assessment of his/her sleep, sleep duration,
      efficacy of routine sleep, sleep disorders, use of hypnotic medication, and
      dysfunction in daily activities. RESULTS: Circadian rhythm sleep disorder was
      more frequent in MS patients relative to healthy subjects (P: 0.002). It was
      higher in MS patients with severe fatigue relative to MS patients with mild
      fatigue (P: 0.05). Fatigue severity was 49.9 +/- 8.2 and 22.5 +/- 7.4 in the
      first and second group, respectively. PSQI index was 7.9 +/- 4.5 in patients with
      severe fatigue and 5.9 +/- 4.5 in patients with mild fatigue and 4.5 +/- 2.4 in
      the control group (P: 0.0001). CONCLUSION: Circadian rhythm sleep disorders are
      more frequent in MS patients and those with fatigue. Recognition and management
      of circadian rhythm sleep disorders in MS patients, especially those with fatigue
      may be helpful in improving care of these patients.

PMID- 23961293
TI  - Seizure characteristics in multiple sclerosis patients.
AB  - BACKGROUND: To evaluate seizure characteristic among multiple sclerosis patients
      with coexistent seizure activity compared to control group. MATERIALS AND
      METHODS: This study is a cross-sectional study which was conducted by reviewing
      the clinical records of patients with definite diagnosis of MS according to
      McDonald's criteria from March 2007 to June 2011, who referred to the MS clinic
      of the university. RESULTS: A total of 920 patients with a diagnosis of MS were
      identified, among whom 29 patients (3.15%) with seizure activity (case) due to MS
      with the mean age of 32.6 +/- 6.23 years were analyzed. Also, fifty MS patients
      without any seizure occurrence with the mean age of 33.7 +/- 7.4 years were used
      as our control group. In case group, seizure was general tonic clonic in 23
      patients (79.3%), complex partial in four (13.8%), and simple partial in two
      (5.9%). The 26 available interictal EEGs in MS patients showed abnormal EEG
      pattern in 22 (84.6%) of them, including focal epileptic form discharge or focal
      slowing in 10 (38.5%), generalized discharge (spike-wave, polyspike, or general
      paroxysmal fast activity) in 10 (38.5%), and general slowing activity in 10
      record (38.5%). MRI reviews of the 26 available brain MRIs showed subcortical
      white mater lesions in 22 (84.6%) of patients with seizure. All MRIs were
      performed within one month after the first seizure episode. Amongst 48 available
      MRIs in our control group, 91.7% (44 cases) showed periventricular lesions and in
      8.3% (4 cases) subcortical white matter lesions were reported. CONCLUSION: The
      result of this study demonstrated the higher rate of subcortical whit matter
      lesion in MS patients with seizure occurrence compared to control group.

PMID- 23961294
TI  - Does levetircetam decrease of the rubral tremor in patients with multiple
      sclerosis.
AB  - BACKGROUND: One of the frequent symptoms of Multiple Sclerosis (MS) is tremor
      which can severely cause disability. Treatment of tremor in MS patients is still
      very challenging to manage. In this study, we sought to determine the efficacy of
      Levetiracetam on treatment of MS-related tremor. MATERIALS AND METHODS: This
      clinical trial study was conducted among 22 patients from July 2012 to April 2012
      in Alzahra-Hospital, Isfahan, Iran. Patients were given 500 mg Levetiracetam
      twice a day for 1 week. The drug dosage increased 1000 mg per week until reaching
      the peak dose of 50 mg/kg. After a 2 week period of washout, first phase was
      repeated. The subjects were assessed at baseline, after first intervention, after
      wash-out period, and after second intervention. RESULTS: A total of 20 patients
      (17 females and 3 males) were enrolled in our study. There was a significant
      difference among tremor rate before and after intervention (P = 0.001). The drug
      was well tolerated and without any serious side effect during follow-up.
      CONCLUSION: Our findings suggest that although Levetiracetam caused a decrease
      tremor rate in MS it surged again after washout period.

PMID- 23961296
TI  - Spinal subarachnoid hemorrhage accompanied with intraventricular hemorrhage.
AB  - Spinal hematoma is a rare and usually severe neurological disorder that, without
      adequate treatment, often leads to death or permanent neurological deficit.
      Epidural as well as subdural and subarachnoid hematomas have been investigated in
      some studies. A 66-year-old man referred to our hospital because of acute onset
      paraplegia and incontinency started 3 h before admission. With impression of
      spinal hemorrhage, emergent cervicothoracic spinal MRI performed. On magnetic
      resonance imagination (MRI) mixed hyper/iso intense lesion in anterior
      subarachnoid space from C7 to T5 was seen. On brain A computerised tomography
      (CT) scan, subarachnoid hemorrhage and intraventricular hemorrhage in posterior
      parts of brain was seen. Unfortunately, the patient died 10 days later. About our
      patient, severe back pain accompanying by immediate paraplegia, sphincter
      disturbances, sensory level, and prominent meningeal signs guided us clinically
      to spinal subarachnoid hemorrhage. Further brain CT scan revealed diffusion of
      blood to brain subarachnoid space and ventricles. An outstanding finding on brain
      CT was the presence of blood only in posterior horn of lateral ventricles and
      dorsal fissures of brain supporting our theory that blood has diffused from
      spinal subarachnoid space to dorsal subarachnoid space of brain because of supine
      position of patient. In this patient anticoagulation may be the only sinister
      factor for developing complications. 

PMID- 23961295
TI  - A quick review of carbamazepine pharmacokinetics in epilepsy from 1953 to 2012.
AB  - BACKGROUND: Carbamazepine has been used as AEDs since 1965, and is most effective
      against partial seizures. Two basic mechanisms of action have been proposed: 1)
      enhancement of sodium channel inactivation by reducing high-frequency repetitive
      firing of action potentials, 2) and action on synaptic transmission. The aim of
      this study was to provide a review of carbamazepine pharmacokinetics and its
      management guidelines in Iranian epileptic population. MATERIALS AND METHODS:
      Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA
      (EBSCO), Web of Science were searched; 1600, 722 and 167 research and review
      articles relevant to the topics; carbamazepine pharmacokinetics, carbamazepine
      pharmacokinetics in epilepsy and review on carbamazepine pharmacokinetics in
      epilepsy were found, respectively. RESULTS: Carbamazepine is highly bound to
      plasma proteins. In patients the protein-bound fraction ranged from 75-80% of the
      total plasma concentration. Bioavailability ranges from 75-85%. The rate or
      extent of absorption was not be affected by food. It is completely metabolized
      and the main metabolite is carbamazepine-epoxide (CBZ-E). Carbamazepine induces
      its own metabolism, leading to increased clearance, shortened serum half-life,
      and progressive decrease in serum levels. Increases in daily dosage are necessary
      to maintain plasma concentration. Severe liver dysfunction may cause disordered
      pharmacokinetics. In cardiac failure, congestion of major vital organs, including
      kidneys, may result in abnormally slow absorption and metabolism. CONCLUSION:
      Carbamazepine shows variability due to its narrow therapeutic window. Therefore
      clinical management in a3n Iranian epileptic population should focus on results
      derived from therapeutic drug monitoring in order to reduce inter and intra-
      individual variability in plasma drug concentrations.

PMID- 23961297
TI  - Jacksonian seizure as the relapse symptom of multiple sclerosis.
AB  - Epilepsy is more common in patients with multiple sclerosis (MS) than in the
      general population, occurring in 2-3% of patients. Convulsions may be either
      tonic-clonic in nature or partial complex. In these individuals, seizures most
      likely result from lesions present in the cerebral cortex and subcortical white
      matter. A Jacksonian seizure is a type of simple partial seizure characterized by
      abnormal movements that begin in one group of muscles and progress to adjacent
      groups of muscles. We describe a case of Jacksonian seizure as the relapse
      symptom of MS. Focal motor seizures of this patient have been observed before and
      presumably marking the clinical onset or during acute bouts of MS. In this case,
      Jacksonian seizures appear to be the sign of a flare of MS, while the majority of
      seizures had been reported occur unrelated to MS relapses. 

PMID- 23961298
TI  - Brain radiation and possible presentation of multiple sclerosis.
AB  - Radiation therapies are commonly used for malignant or metastatic brain tumors
      for curative and palliative use. The radiation-induced neurotoxicity includes
      both parenchymal and vascular damage. Here we report the case of a 43-year-old
      woman who developed Multiple sclerosis (MS) 9 months after she underwent the last
      session of radiotherapy for the diagnosed meningioma. Conventional doses of
      radiation might trigger MS. 

PMID- 23961299
TI  - Lumped Element Electrical Model based on Three Resistors for Electrical Impedance
      in Radiofrequency Cardiac Ablation: Estimations from Analytical Calculations and
      Clinical Data.
AB  - The electrical impedance measured during radiofrequency cardiac ablation (RFCA)
      is widely used in clinical studies to predict the heating evolution and hence the
      success of the procedure. We hypothesized that a model based on three resistors
      in series can mimic the total electrical impedance measured during RFCA. The
      three resistors or impedances are given by: impedance associated with the tissue
      around the active electrode (myocardium and circulating blood) (Z-A), that
      associated with the tissue around the dispersive electrode (Z-DE) and that
      associated with the rest of the body (Z-B). Our objective was to quantify the
      values associated with these three impedance types by an analytical method, after
      which the values obtained would be compared to those estimated from clinical data
      from previous studies. The results suggest that an RFCA using a 7 Fr 4-mm
      electrode would give a Z-A of around 75 ohms, a Z-DE around 20 ohms, and Z-B
      would be 15+/-10 ohms (for body surface area variations between 1.5 and 2.5 m^2).
      Finally, adaptations of the proposed model were used to explain the results of
      previous clinical studies using a different electrode arrangement, such as in
      bipolar ablation of the ventricular septum. 

PMID- 23961300
TI  - Disc height and sagittal alignment in operated and non-operated levels in the
      lumbar spine at long-term follow-up: a case-control study.
AB  - PURPOSE: To compare lumbar disc degeneration at 9-year follow-up in patients with
      chronic low back pain who had instrumented lumbar fusion or no fusion. MATERIAL
      AND METHODOLOGY: The main outcomes were disc height and sagittal alignment
      measured by Distortion Compensated Roentgen Analysis (DCRA). Secondary outcome
      included the Oswestry Disability Index and VAS back pain. RESULTS: Forty-eight
      patients with baseline and 9-year radiographs from L2- S1 were included. Twenty
      three had lumbar fusion and 25 had no fusion. Disc height was reduced at all
      levels independent of fusion. No difference in disc height and sagittal alignment
      was observed between patients fused and not fused. There were weak correlations,
      ranging from 0.04 to 0.36, between clinical and radiological parameters.
      CONCLUSION: Lumbar disc degeneration increased at all measured levels independent
      of fusion and correlated poorly with clinical outcome.

PMID- 23961301
TI  - A complication during femoral broaching in total hip arthroplasty: a case report.
AB  - Press-fit component fixation is one of the primary goals in uncemented total hip
      arthroplasty. When aiming at proximal load transfer, the stem size has to be
      selected with regard to the shape of the proximal femoral canal. This can be
      challenging in patients with 'champagne flute' femurs with a relatively narrow
      diaphysis, especially when a long stem femoral component is used. The present
      case report describes a complication during femoral broaching for a primary
      uncemented femoral component. Because of the narrow diaphysis, the distal portion
      of the broach got caught in the narrow canal and it became impossible to remove
      the broach with conventional techniques. Via a second distal incision, the femur
      was split from the distal tip of the broach to approximately 5 cm distal of the
      femoral neck cut along the posterior aspects of the femur. This loosened the
      broach enough to allow for an uncomplicated removal. The longitudinal split was
      secured with cables before a similar size primary implant was press fitted into
      the femoral canal. 

PMID- 23961302
TI  - Inhibition of HIV-1 Replication by Secondary Metabolites From Endophytic Fungi of
      Desert Plants.
AB  - Most antiretroviral drugs currently in use to treat an HIV-1 infection are
      chemically synthesized and lead to the development of viral resistance, as well
      as cause severe toxicities. However, a largely unexplored source for HIV-1 drug
      discovery is endophytic fungi that live in a symbiotic relationship with plants.
      These fungi produce biologically active secondary metabolites, which are natural
      products that are beneficial to the host. We prepared several hundred extracts
      from endophytic fungi of desert plants and evaluated the inhibitory effects on
      HIV-1 replication of those extracts that showed less than 30% cytotoxicity in T
      lymphocytes. Those extracts that inhibited viral replication were fractionated in
      order to isolate the compounds responsible for activity. Multiple rounds of
      fractionation and antiviral evaluation lead to the identification of four
      compounds, which almost completely impede HIV-1 replication. These studies
      demonstrate that metabolites from endophytic fungi of desert plants can serve as
      a viable source for identifying potent inhibitors of HIV-1 replication. 

PMID- 23961303
TI  - Morphology of optic disc through heidelberg retina tomograph in retinal vein
      occlusions alone or in combination with primary open angle glaucoma.
AB  - PURPOSE: To evaluate the morphology of optic discs in eyes suffering from retinal
      vein occlusion (RVO) alone or in combination with primary open-angle glaucoma
      (POAG). METHODS: Prospective, observational study. 48 consecutive patients were
      enrolled, 30 with unilateral RVO diagnosis, 18 with unilateral retinal vein
      occlusion (RVO) associated with POAG. We divided RVOs on the basis of occlusion
      site: arterio-venous crossing (AV-RVO), optic cup (OC-RVO), optic nerve (ON-RVO)
      with head nerve swelling (ONHS-RVO) or without it (NONHS-RVO). A control group of
      25 patients who were sex and age matched was selected. RESULTS: Comparing the
      fellow eyes of the patients with RVO and control healthy eyes, no differences
      emerged in cup/disc ratio but they came out for the HRT values in Rim Area, cup
      shape measure and height variation contour (p<0.05). The most frequent occlusion
      site was at the level of an arteriovenous crossing in patients not suffering from
      POAG (36.7%) and at the level of the optic cup in patients with RVO and POAG
      (50%). In the RVO group without POAG, the OC-RVO subgroup has shown an higher cup
      area (0.366+/-0.094) and cup/disc area ratio (0.184+/-0.063), a lower rim volume
      (0.374+/-0.021) and a different cup shape measure (-0.221+/-0.066) (p<0.05)
      compared with the AV and NONHS sites. Compared with NONHS group differences
      emerged also for the fibres parameters and in the height variation contour
      (0.346+/-0.081). Also in the RVO group with POAG significant differences (p<0.05)
      have been surveyed between OC-RVO and other occlusion sites in cup area (0.119+/
      0.029), cup/disc area ratio (0.532+/-0.09), rim volume (0.374+/-0.07), cup/shape
      measure (-0.079+/-0.013). CONCLUSIONS: Classification of the analyzed parameters
      on the basis of the occlusion site provides a basis for which clinical decisions
      and research on causal factors in future studies can be based on.

PMID- 23961304
TI  - A case report of xanthogranulomatous osteomyelitis of the distal ulna mimicking a
      malignant neoplasm.
AB  - PATIENT: Male, 59 FINAL DIAGNOSIS: Xanthogranulomatous osteomyelitis Symptoms:
      Painful swelling in the wrist Medication: Drug history of antifulgal agents
      Clinical Procedure: Excisional biopsy Specialty: Radiology. OBJECTIVE: Rare
      disease. BACKGROUND: Xanthogranulomatous inflammation is a chronic inflammatory
      disease in which bone involvement is extremely rare. Bone involvement of
      xanthogranulomatous inflammation, termed xanthogranulomatous osteomyelitis (XO),
      often presents as a mass-like lesion extending to adjacent structures, which can
      mimic infiltrative carcinoma. CASE REPORT: We present a case of XO in the ulna,
      which mimicked a neoplasm. A 59-year-old man presented with a 2-month history of
      painful swelling in the right wrist. Plain radiography and CT showed an
      osteolytic lesion at the distal ulna. MRI revealed a soft-tissue mass with
      lobulated margins and contrast enhancement. Intense uptake in bone scan and PET
      suggested malignancy. An excisional biopsy from the representative area resulted
      in a pathology diagnosis of XO. CONCLUSIONS: Gross and radiologic manifestations
      of XO can mimic neoplasm. XO generally has benign prognosis, contrary to
      malignant bone tumor. Therefore, biopsy and histopathological confirmation are
      necessary for proper management.

PMID- 23961305
TI  - Posttraumatic persistent shoulder pain: Superior labrum anterior-posterior (SLAP)
      lesions.
AB  - PATIENT: Male, 57 FINAL DIAGNOSIS: Typ 2 Superior labrum anterior-posterior
      lesion Symptoms: Shoulder pain after trauma Medication: - Clinical Procedure: -
      Specialty: Orthopedics and Traumatology * Emergency Medicine. OBJECTIVE: Rare
      disease. BACKGROUND: Due to the anatomical and biomechanical characteristics of
      the shoulder, traumatic soft-tissue lesions are more common than osseous lesions.
      Superior labrum anterior-posterior (SLAP) lesions are an uncommon a cause of
      shoulder pain. SLAP is injury or separation of the glenoid labrum superior where
      the long head of biceps adheres. SLAP lesions are usually not seen on plain
      direct radiographs. Shoulder MRI and magnetic resonance arthrography are useful
      for diagnosis. CASE REPORT: A 57-year-old man was admitted to the emergency
      department due to a low fall on his shoulder. In physical examination, active and
      passive shoulder motion was normal except for painful extension. Anterior
      posterior shoulder x-ray imaging was normal. The patient required orthopedics
      consultation in the emergency observation unit due to persistent shoulder pain.
      In shoulder MRI, performed for diagnosis, type II lesion SLAP was detected. The
      patient was referred to a tertiary hospital due to lack of arthroscopy in our
      hospital. CONCLUSIONS: Shoulder traumas are usually soft-tissue injuries with no
      findings in x-rays. SLAP lesion is an uncommon cause of traumatic shoulder pain.
      For this reason, we recommend orthopedic consultation in post-traumatic
      persistent shoulder pain.

PMID- 23961306
TI  - L-asparaginase fatal toxic encephalopathy during consolidation treatment in an
      adult with acute lymphoblastic leukemia.
AB  - PATIENT: Male, 51 FINAL DIAGNOSIS: Encephalopaty toxic Symptoms: Confusion *
      disorientation * drowsiness * fever MEDICATION: L-asparaginase Clinical
      Procedure: - Specialty: Oncology. OBJECTIVE: Unknown ethiology. BACKGROUND: Novel
      therapies have improved survival in malignancies of lymphoid origin. This
      improvement, however, has been at the cost of chemotherapy-related toxicities. L
      asparaginase is frequently included in combination chemotherapies for acute
      lymphoblastic leukemia. Its use is frequently limited by significant adverse
      effects, such as coagulation abnormalities and cerebrovascular complications. L
      asparaginase-associated encephalopathy is most often observed during the
      induction phase of chemotherapy and usually carries a favorable prognosis. CASE
      REPORT: We describe the profile of an adult with acute lymphoblastic leukemia
      treated with L-asparaginase, who developed toxic leukoencephalopathy during the
      second phase of consolidation treatment. He presented with decreased level of
      consciousness, which progressed to deep coma and finally brain death. MRI
      disclosed extensive lesions, consistent with toxic encephalopathy. CONCLUSIONS:
      Even mild neurological symptoms should raise suspicion of these possibly fatal
      chemotherapy related toxicities.

PMID- 23961307
TI  - Non-contiguous finished genome sequence and description of Brevibacillus
      massiliensis sp. nov.
AB  - Brevibacillus massiliensis strain phR(T) sp. nov. is the type strain of B.
      massiliensis sp. nov., a new species within the genus Brevibacillus. This strain
      was isolated from the fecal flora of a woman suffering from morbid obesity. B.
      massiliensis is a Gram-positive aerobic rod-shaped bacterium. Here we describe
      the features of this organism, together with the complete genome sequence and
      annotation. The 5,051,018 bp long genome (1 chromosome but no plasmid) contains
      5,051 protein-coding and 84 RNA genes, and exhibits a G+C content of 53.1%. 

PMID- 23961308
TI  - Complete genome sequence of Coriobacterium glomerans type strain (PW2(T)) from
      the midgut of Pyrrhocoris apterus L. (red soldier bug).
AB  - Coriobacterium glomerans Haas and Konig 1988, is the only species of the genus
      Coriobacterium, family Coriobacteriaceae, order Coriobacteriales, phylum
      Actinobacteria. The bacterium thrives as an endosymbiont of pyrrhocorid bugs,
      i.e. the red fire bug Pyrrhocoris apterus L. The rationale for sequencing the
      genome of strain PW2(T) is its endosymbiotic life style which is rare among
      members of Actinobacteria. Here we describe the features of this symbiont,
      together with the complete genome sequence and its annotation. This is the first
      complete genome sequence of a member of the genus Coriobacterium and the sixth
      member of the order Coriobacteriales for which complete genome sequences are now
      available. The 2,115,681 bp long single replicon genome with its 1,804 protein
      coding and 54 RNA genes is part of the G enomic E ncyclopedia of Bacteria and
      Archaea project. 

PMID- 23961309
TI  - Complete genome sequence of the bile-resistant pigment-producing anaerobe
      Alistipes finegoldii type strain (AHN2437(T)).
AB  - Alistipes finegoldii Rautio et al. 2003 is one of five species of Alistipes with
      a validly published name: family Rikenellaceae, order Bacteroidetes, class
      Bacteroidia, phylum Bacteroidetes. This rod-shaped and strictly anaerobic
      organism has been isolated mostly from human tissues. Here we describe the
      features of the type strain of this species, together with the complete genome
      sequence, and annotation. A. finegoldii is the first member of the genus
      Alistipes for which the complete genome sequence of its type strain is now
      available. The 3,734,239 bp long single replicon genome with its 3,302 protein
      coding and 68 RNA genes is part of the G enomic E ncyclopedia of Bacteria and
      Archaea project. 

PMID- 23961310
TI  - High-quality-draft genome sequence of the yellow-pigmented flavobacterium
      Joostella marina type strain (En5(T)).
AB  - At present, Joostella marina Quan et al. 2008 is the sole species with a validly
      published name in the genus Joostella, family Flavobacteriacae, phylum
      Bacteriodetes. It is a yellow-pigmented, aerobic, marine organism about which
      little has been reported other than the chemotaxonomic features required for
      initial taxonomic description. The genome of J. marina strain En5(T) complements
      a list of 16 Flavobacteriaceae strains for which complete genomes and draft
      genomes are currently available. Here we describe the features of this bacterium,
      together with the complete genome sequence, and annotation. This is the first
      member of the genus Joostella for which a complete genome sequence becomes
      available. The 4,508,243 bp long single replicon genome with its 3,944 protein
      coding and 60 RNA genes is part of the G enomic E ncyclopedia of Bacteria and
      Archaea project. 

PMID- 23961311
TI  - Complete genome sequence of the moderate thermophile Anaerobaculum mobile type
      strain (NGA(T)).
AB  - Anaerobaculum mobile Menes and Muxi 2002 is one of three described species of the
      genus Anaerobaculum, family Synergistaceae, phylum Synergistetes. This anaerobic
      and motile bacterium ferments a range of carbohydrates and mono- and dicarboxylic
      acids with acetate, hydrogen and CO2 as end products. A. mobile NGA(T) is the
      first member of the genus Anaerobaculum and the sixth member of the phylum
      Synergistetes with a completely sequenced genome. Here we describe the features
      of this bacterium, together with the complete genome sequence, and annotation.
      The 2,160,700 bp long single replicon genome with its 2,053 protein-coding and 56
      RNA genes is part of the G enomic E ncyclopedia of Bacteria and Archaea project. 

PMID- 23961312
TI  - Complete genome sequence of Desulfocapsa sulfexigens, a marine
      deltaproteobacterium specialized in disproportionating inorganic sulfur
      compounds.
AB  - Desulfocapsa sulfexigens SB164P1 (DSM 10523) belongs to the deltaproteobacterial
      family Desulfobulbaceae and is one of two validly described members of its genus.
      This strain was selected for genome sequencing, because it is the first marine
      bacterium reported to thrive on the disproportionation of elemental sulfur, a
      process with a unresolved enzymatic pathway in which elemental sulfur serves both
      as electron donor and electron acceptor. Furthermore, in contrast to its
      phylogenetically closest relatives, which are dissimilatory sulfate-reducers, D.
      sulfexigens is unable to grow by sulfate reduction and appears metabolically
      specialized in growing by disproportionating elemental sulfur, sulfite or
      thiosulfate with CO2 as the sole carbon source. The genome of D. sulfexigens
      contains the set of genes that is required for nitrogen fixation. In an acetylene
      assay it could be shown that the strain reduces acetylene to ethylene, which is
      indicative for N-fixation. The circular chromosome of D. sulfexigens SB164P1
      comprises 3,986,761 bp and harbors 3,551 protein-coding genes of which 78% have a
      predicted function based on auto-annotation. The chromosome furthermore encodes
      46 tRNA genes and 3 rRNA operons. 

PMID- 23961313
TI  - Genome analysis of Desulfotomaculum kuznetsovii strain 17(T) reveals a
      physiological similarity with Pelotomaculum thermopropionicum strain SI(T).
AB  - Desulfotomaculum kuznetsovii is a moderately thermophilic member of the
      polyphyletic spore-forming genus Desulfotomaculum in the family Peptococcaceae.
      This species is of interest because it originates from deep subsurface thermal
      mineral water at a depth of about 3,000 m. D. kuznetsovii is a rather versatile
      bacterium as it can grow with a large variety of organic substrates, including
      short-chain and long-chain fatty acids, which are degraded completely to carbon
      dioxide coupled to the reduction of sulfate. It can grow methylotrophically with
      methanol and sulfate and autotrophically with H2 + CO2 and sulfate. For growth it
      does not require any vitamins. Here, we describe the features of D. kuznetsovii
      together with the genome sequence and annotation. The chromosome has 3,601,386 bp
      organized in one contig. A total of 3,567 candidate protein-encoding genes and 58
      RNA genes were identified. Genes of the acetyl-CoA pathway, possibly involved in
      heterotrophic growth with acetate and methanol, and in CO2 fixation during
      autotrophic growth are present. Genomic comparison revealed that D. kuznetsovii
      shows a high similarity with Pelotomaculum thermopropionicum. Genes involved in
      propionate metabolism of these two strains show a strong similarity. However,
      main differences are found in genes involved in the electron acceptor metabolism.

PMID- 23961315
TI  - Meeting report: 1st international functional metagenomics workshop may 7-8, 2012,
      st. Jacobs, ontario, Canada.
AB  - This report summarizes the events of the 1(st) International Functional
      Metagenomics Workshop. The workshop was held on May 7 and 8, 2012, in St. Jacobs,
      Ontario, Canada and was focused on building an international functional
      metagenomics community, exploring strategic research areas, and identifying
      opportunities for future collaboration and funding. The workshop was initiated by
      researchers at the University of Waterloo with support from the Ontario Genomics
      Institute (OGI), Natural Sciences and Engineering Research Council of Canada
      (NSERC) and the University of Waterloo. 

PMID- 23961314
TI  - Genome sequence of the thermophilic fresh-water bacterium Spirochaeta caldaria
      type strain (H1(T)), reclassification of Spirochaeta caldaria, Spirochaeta
      stenostrepta, and Spirochaeta zuelzerae in the genus Treponema as Treponema
      caldaria comb. nov., Treponema stenostrepta comb. nov., and Treponema zuelzerae
      comb. nov., and emendation of the genus Treponema.
AB  - Spirochaeta caldaria Pohlschroeder et al. 1995 is an obligately anaerobic, spiral
      shaped bacterium that is motile via periplasmic flagella. The type strain, H1(T),
      was isolated in 1990 from cyanobacterial mat samples collected at a freshwater
      hot spring in Oregon, USA, and is of interest because it enhances the degradation
      of cellulose when grown in co-culture with Clostridium thermocellum. Here we
      provide a taxonomic re-evaluation for S. caldaria based on phylogenetic analyses
      of 16S rRNA sequences and whole genomes, and propose the reclassification of S.
      caldaria and two other Spirochaeta species as members of the emended genus
      Treponema. Whereas genera such as Borrelia and Sphaerochaeta possess well
      distinguished genomic features related to their divergent lifestyles, the
      physiological and functional genomic characteristics of Spirochaeta and Treponema
      appear to be intermixed and are of little taxonomic value. The 3,239,340 bp long
      genome of strain H1(T) with its 2,869 protein-coding and 59 RNA genes is a part
      of the G enomic E ncyclopedia of Bacteria and Archaea project. 

PMID- 23961316
TI  - The Hospital Microbiome Project: Meeting Report for the 1st Hospital Microbiome
      Project Workshop on sampling design and building science measurements, Chicago,
      USA, June 7th-8th 2012.
AB  - This report details the outcome of the 1st Hospital Microbiome Project workshop
      held on June 7th-8th, 2012 at the University of Chicago, USA. The workshop was
      arranged to determine the most appropriate sampling strategy and approach to
      building science measurement to characterize the development of a microbial
      community within a new hospital pavilion being built at the University of Chicago
      Medical Center. The workshop made several recommendations and led to the
      development of a full proposal to the Alfred P. Sloan Foundation as well as to
      the creation of the Hospital Microbiome Consortium. 

PMID- 23961317
TI  - Meeting report: fungal its workshop (october 2012).
AB  - This report summarizes a meeting held in Boulder, CO USA (19-20 October 2012) on
      fungal community analyses using ultra-high-throughput sequencing of the internal
      transcribed spacer (ITS) region of the nuclear ribosomal RNA (rRNA) genes. The
      meeting was organized as a two-day workshop, with the primary goal of supporting
      collaboration among researchers for improving fungal ITS sequence resources and
      developing recommendations for standard ITS primers for the research community. 

PMID- 23961318
TI  - Status of autoimmune diabetes 20-year after generation of BDC2.5-TCR transgenic
      non-obese diabetic mouse.
AB  - Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction
      of insulin-producing beta cells by autoreactive T cells, leading to lifelong
      dependency on insulin therapy and increased risk of long-term cardiovascular
      complications. Here we take the opportunity of the 20(th) anniversary of the
      generation of the BDC2.5 TCR transgenic non-obese diabetic (NOD) mouse model, to
      provide a brief overview of the significant progress that has been made in
      understanding the role of T cells in the disease pathogenesis period. This
      included development of hundreds of reagents that block or even reverse new-onset
      disease by directly or indirectly controlling T cells. We also reflect on the
      sobering fact that none of these strategies has shown significant efficacy in
      clinical trials and discuss potential reasons hindering translation of the
      preclinical findings into successful therapeutic strategies and potential ways
      forward. 

PMID- 23961319
TI  - Trace elements in diabetic cardiomyopathy: An electrophysiological overview.
AB  - There is a growing body of evidence that Diabetes Mellitus leads to a specific
      cardiomyopathy apart from vascular disease and bring about high morbidity and
      mortality throughout the world. Recent clinical and experimental studies have
      extensively demonstrated that this cardiomyopathy causes impaired cardiac
      performance manifested by early diastolic and late systolic dysfunction. This
      impaired cardiac performance most probably have emerged upon the expression and
      activity of regulatory proteins such as Na(+)/Ca(2+) exchanger, sarcoplasmic
      reticulum Ca(2+)-ATPase, ryanodine receptor and phospholamban. Over years many
      therapeutic strategies have been recommended for treatment of diabetic
      cardiomyopathy. Lately, inorganic elements have been suggested to have anti
      diabetic effects due to their suggested ability to regulate glucose homeostasis,
      reduce oxidative stress or suppress phosphatases. Recent findings have shown that
      trace elements exert many biological effects including insulin-mimetic or
      antioxidant activity and in this manner they have been recommended as potential
      candidates for treatment of diabetes-induced cardiac complications, an effect
      based on their modes of action. Some of these trace elements are known to play an
      essential role as component of enzymes and thus modulate the organ function in
      physiological and pathological conditions. Besides, they can also manipulate
      redox state of the channels via antioxidant properties and thus contribute to the
      regulation of [Ca(2+)]i homeostasis and cardiac ion channels. On account of
      little information about some trace elements, we discussed the effect of
      vanadium, selenium, zinc and tungstate on diabetic heart complications. 

PMID- 23961320
TI  - Biomolecular basis of the role of diabetes mellitus in osteoporosis and bone
      fractures.
AB  - Osteoporosis has become a serious health problem throughout the world which is
      associated with an increased risk of bone fractures and mortality among the
      people of middle to old ages. Diabetes is also a major health problem among the
      people of all age ranges and the sufferers due to this abnormality increasing day
      by day. The aim of this review is to summarize the possible mechanisms through
      which diabetes may induce osteoporosis. Diabetes mellitus generally exerts its
      effect on different parts of the body including bone cells specially the
      osteoblast and osteoclast, muscles, retina of the eyes, adipose tissue, endocrine
      system specially parathyroid hormone (PTH) and estrogen, cytokines, nervous
      system and digestive system. Diabetes negatively regulates osteoblast
      differentiation and function while positively regulates osteoclast
      differentiation and function through the regulation of different intermediate
      factors and thereby decreases bone formation while increases bone resorption.
      Some factors such as diabetic neuropathy, reactive oxygen species, Vitamin D, PTH
      have their effects on muscle cells. Diabetes decreases the muscle strength
      through regulating these factors in various ways and ultimately increases the
      risk of fall that may cause bone fractures. 

PMID- 23961321
TI  - Genetics of type 2 diabetes.
AB  - Type 2 diabetes (T2D) is the result of interaction between environmental factors
      and a strong hereditary component. We review the heritability of T2D as well as
      the history of genetic and genomic research in this area. Very few T2D risk genes
      were identified using candidate gene and linkage-based studies, but the advent of
      genome-wide association studies has led to the identification of multiple genes,
      including several that were not previously known to play any role in T2D. Highly
      replicated genes, for example TCF7L2, KCNQ1 and KCNJ11, are discussed in greater
      detail. Taken together, the genetic loci discovered to date explain only a small
      proportion of the observed heritability. We discuss possible explanations for
      this "missing heritability", including the role of rare variants, gene
      environment interactions and epigenetics. The clinical utility of current
      findings and avenues of future research are also discussed. 

PMID- 23961322
TI  - Diabetic nephropathy: Treatment with phosphodiesterase type 5 inhibitors.
AB  - The importance of nitric oxide (NO) in vascular physiology is irrefutable; it
      stimulates the intracellular production of cyclic guanosine monophosphate (cGMP),
      initiating vascular smooth muscle relaxation. This biochemical process increases
      the diameter of small arteries, regulating blood flow distribution between
      arterioles and the microvasculature. The kidney is no exception, since NO
      predominantly dilates the glomerular afferent arterioles. It is now evident that
      the vascular production of cGMP can be augmented by inhibitors of
      phosphodiesterase type 5 (PDE 5), the enzyme which breakdowns this cyclic
      nucleotide. This has clinical relevance, since diabetic nephropathy (DN) a major
      microvascular complication of diabetes mellitus and the most common cause of end
      stage renal disease, increases intraglomerular capillary pressure, leading to
      glomerular hypertension. PDE 5 inhibitors may have, therefore, the potential to
      reduce glomerular hypertension. This review describes the use of PDE 5 inhibitors
      to improve the metabolic, haemodynamic and inflammatory pathways/responses, all
      of which are dysfunctional in DN. 

PMID- 23961323
TI  - Type 1 diabetes and celiac disease: The effects of gluten free diet on metabolic
      control.
AB  - Type 1 diabetes mellitus is associated with celiac disease, with a prevalence
      that varies between 0.6% and 16.4%, according to different studies. After a
      diagnosis of celiac disease is confirmed by small bowel biopsy, patients are
      advised to commence a gluten-free diet (GFD). This dietary restriction may be
      particularly difficult for the child with diabetes, but in Europe (and in Italy)
      many food stores have targeted this section of the market with better labeling of
      products and more availability of specific GFD products. Treatment with a GFD in
      symptomatic patients has been shown to improve the symptoms, signs and
      complications of celiac disease. However, the effects of a GFD on diabetic
      control are less well established. Initial reports of improved hypoglycemic
      control were based on children who were diagnosed with celiac disease associated
      with malabsorption, but there have subsequently been reports of improvement in
      patients with type 1 diabetes with subclinical celiac disease. There are other
      studies reporting no effect, improved control and an improvement of hypoglycemic
      episodes. Moreover, in this review we wish to focus on low glycemic index foods,
      often suggested in people with type 1 diabetes, since they might reduce
      postprandial glycemic excursion and enhance long-term glycemic control. In
      contrast, GFD may be rich in high glycemic index foods that can increase the risk
      of obesity, insulin resistance and cardiovascular disease, worsening the
      metabolic control of the child with diabetes. Hence, it is important to evaluate
      the impact of a GFD on metabolic control, growth and nutritional status in
      children with type 1 diabetes. 

PMID- 23961324
TI  - Association of comorbidities with increasing severity of peripheral neuropathy in
      diabetes mellitus.
AB  - AIM: To analyze a large population of patients with diabetes and peripheral
      neuropathy (PN) to determine other meaningful comorbid etiologies for PN.
      METHODS: Peripheral Neuropathy is a common complication of type 1 and 2 diabetes
      mellitus; however, other potential causes for PN may be co-existing in patients
      with diabetes. A prospective cohort study was performed to assess patients with
      diabetes and PN. We compared patients having PN due solely to diabetes with
      patients possessing co-existing comorbidities, performing clinical (Toronto
      Clinical Scoring System and the Utah Early Neuropathy Scale), laboratory and
      electrophysiological assessments in all patients. RESULTS: Patients with either
      type 1 or 2 diabetes mellitus and co-existing comorbidities did not have more
      severe clinical or electrophysiological PN phenotypes overall. However, in
      patients with type 1 diabetes, presence of a lipid disorder was associated with
      greater PN severity. In type 2 diabetes patients, both a lipid disorder and
      cobalamin deficiency were associated with greater PN severity. There was no
      additive effect upon PN severity with presence of three or more comorbid
      etiologies. CONCLUSION: The presence of specific, and not general, comorbidities
      in patients with type 1 or 2 diabetes corresponds with greater PN severity.

PMID- 23961325
TI  - Diabetes-related impairment in bone strength is established early in the life
      course.
AB  - AIM: To evaluate properties of bone quantity/quality using young non-obese Type 1
      (T1D)-diabetic (NOD) prone and syngenic non-diabetic (NOD.scid) mice. METHODS:
      Quantitative bone assessment of tibia was conducted using dual-energy X-ray
      absorptiometry (DXA) for the evaluation of body mass, bone mineral content, body
      fat mass and lean mass. Qualitative assessment was accomplished by three-point
      breakage for assessment of force to failure and micro-computed tomography for
      evaluation of trabecular and cortical properties of bone. In addition, fasting
      blood was evaluated prior to sacrifice at week eleven and fifteen to evaluate and
      compare glucose homeostasis between the strains of mice. RESULTS: Our findings
      support a perturbation in the relationship between bone quantity, quality, and
      subsequently, the association between structure and strength. There were no
      differences in DXA-assessed body composition (body fat, % fat mass and lean mass)
      and bone composition (bone mineral content and bone mineral density) between
      strains. However, relative to NOD.scid, NOD mice had lower trabecular bone
      volume, relative trabecular bone volume, trabecular number and trabecular total
      material density (P < 0.05). Conversely, NOD mice had greater cortical total mean
      volume (P < 0.05). General linear models analysis adjusted for body weight
      revealed a significant contribution of T1D to bone health as early as 5 wk.
      CONCLUSION: It is well-established that diabetes is a significant risk factor for
      increased fractures, although the underlying mechanisms are not fully understood.
      Investigation of bone parameters encompassing strength and structure early in the
      life course will facilitate the elucidation of the pathogenesis of impaired bone
      integrity.

PMID- 23961326
TI  - Vildagliptin-insulin combination improves glycemic control in Asians with type 2
      diabetes.
AB  - AIM: To assess the efficacy and safety of vildagliptin 50 mg bid as add-on
      therapy to insulin in Asian patients with type 2 diabetes mellitus (T2DM).
      METHODS: This was a post hoc analysis of a subgroup of Asian patients from a
      multicenter, randomized, double-blind, placebo-controlled, parallel-group study
      in T2DM patients inadequately controlled by stable insulin therapy, with or
      without metformin. A total of 173 patients were randomized 1:1 to receive
      treatment with vildagliptin 50 mg bid (n = 87) or placebo (n = 86) for 24 wk.
      Changes in HbA1c and fasting plasma glucose (FPG), from baseline to study
      endpoint, were analyzed using an analysis of covariance model. Change from
      baseline to endpoint in body weight was summarized by treatment. Safety and
      tolerability of vildagliptin was also evaluated. RESULTS: After 24 wk, the
      difference in adjusted mean change in HbA1c between vildagliptin and placebo was
      0.82% (8.96 mmol/mol; P < 0.001) in Asian subgroup, 0.85% (9.29 mmol/mol; P <
      0.001) in patients also receiving metformin, and 0.73% (7.98 mmol/mol; P < 0.001)
      in patients without metformin, all in favor of vildagliptin. There was no
      significant difference in the change in FPG between treatments. Weight was stable
      in both treatment groups (+0.3 kg and -0.2 kg, for vildagliptin and placebo,
      respectively). Overall, vildagliptin was safe and well tolerated with similarly
      low incidences of hypoglycemia (8.0% vs 8.1%) and no severe hypoglycemic events
      were experienced in either group. CONCLUSION: In Asian patients inadequately
      controlled with insulin (with or without concomitant metformin), insulin
      vildagliptin combination treatment significantly reduced HbA1c compared with
      placebo, without an increase in risk of hypoglycemia or weight gain.

PMID- 23961328
TI  - We Should Have Concerns about Risk Transfer.

PMID- 23961327
TI  - Effect of treatment of overt hypothyroidism on insulin resistance.
AB  - AIM: To investigate the impact of hypothyroidism and thyroxine therapy on insulin
      sensitivity in patients with overt hypothyroidism. METHODS: The study included
      twenty seven overtly hypothyroid and fifteen healthy euthyroid South Western
      Asian females. Both groups had matching age and body mass index. Physiological
      and pathological conditions as well as medications that may alter thyroid
      function, glucose homeostasis or serum lipids were ruled out. Serum thyrotropin
      (TSH), free tetraiodothyronine (FT4), free triiodothyronine (FT3), fasting
      insulin (FI), fasting plasma glucose (FPG), total cholesterol and triglycerides
      were measured before and six months after initiating thyroxine therapy for
      hypothyroid patients and once for the control group. Insulin resistance (IR) was
      estimated using homeostasis model assessment (HOMA-IR) and Body mass index (BMI)
      was calculated. RESULTS: Both study groups, hypothyroid patients and euthyroid
      control subjects, had matching age and body mass index (P-value 0.444, 0.607
      respectively). No significant difference was found between the hypothyroid
      patients and the euthyroid control group regarding fasting plasma glucose,
      fasting insulin, insulin resistance, total cholesterol and triglycerides (P
      values 0.432, 0.621, 0.883, 0.586, 0.05 respectively). In the hypothyroid
      patients, triglycerides showed direct correlation to TSH and inverse correlation
      to FT3. Similarly total cholesterol inversely correlated to FT3 but its direct
      correlation to TSH did not reach statistical significance. After thyroxine
      replacement and reaching an euthyroid state as confirmed by clinical and
      laboratory data, there was no significant change in fasting plasma glucose,
      insulin resistance or triglyceride level (P-value 0.216, 0.204, 0.175
      respectively) while total cholesterol significantly decreased (P-value 0.043) and
      fasting insulin significantly increased (P-value 0.047). CONCLUSION:
      Hypothyroidism has no impact on insulin sensitivity. Correction of hypothyroidism
      is not associated with a significant change of insulin sensitivity or
      triglycerides, but with a significant reduction of total cholesterol.

PMID- 23961329
TI  - Essential Occupational Safety and Health Interventions for Low- and Middle-income
      Countries: An Overview of the Evidence.
AB  - There is still a considerable burden of occupational diseases and injuries in the
      world. It is not well known which interventions can effectively reduce the
      exposures at work that cause this burden. The objective of this article is to
      summarize evidence from systematic reviews of interventions to prevent
      occupational diseases and injuries. We included systematic reviews of
      interventions to reduce the incidence of work-related cancer, dust-related
      diseases, occupational asthma, chronic obstructive pulmonary disease,
      noiseinduced hearing loss, back pain, and occupational injuries. We searched
      Medline and Embase with predefined search strategies to locate systematic reviews
      of these interventions. We found 23 systematic reviews of which the results are
      also applicable to low- and middle income countries. Effective measures to reduce
      exposure leading to work-related cancer, dust-related diseases, asthma, chronic
      obstructive pulmonary disease, noise, and injuries are available. However, better
      implementation of these measures is needed. Regulation, enforcement of
      regulation, and incentives for employers are effective interventions to achieve
      this goal. There is evidence that feedback and rewards for workers help in
      reducing occupational injuries. There is no evidence in many studies that back
      pain can be prevented. Personal protective equipment technically has the
      potential to reduce exposure but this is difficult to put into effect. There is
      no evidence in the studies regarding the effectiveness of education and training,
      preventive drugs, or health examinations. There is evidence that the
      implementation of technical measures enforced by regulation can prevent
      occupational diseases and injuries. For other interventions such as education or
      health examinations, there is no evidence that supports their effectiveness. More
      systematic reviews are needed in the area of injury prevention. 

PMID- 23961330
TI  - Awareness of Asbestos and Action Plans for Its Exposure can Help Lives Exposed to
      Asbestos.
AB  - Despite the fact that asbestos is a known carcinogen to humans, it is still used
      in industrialized countries, especially Asian countries. The global incidence of
      asbestos-related diseases (ARDs) due to the past use of asbestos, continues to
      increase, although many countries have adopted a total ban on asbestos use. The
      implementation of effective strategies to eliminate ARDs is therefore an
      important challenge in Asia, where asbestos is still mined and consumed.
      Collaborative efforts and strategies at the local and international levels are
      vital, in the pursuit toward the elimination of ARDs in this region. 

PMID- 23961331
TI  - Psychosocial risks: is risk management strategic enough in business and policy
      making?
AB  - BACKGROUND: In times of continuous change and volatile markets, organizations are
      increasingly characterized by downsizing, work intensification, and resource
      rationalization. This has resulted in diversification, and the emergence of new
      risks within the field of occupational health and safety, with an important
      impact. This paper focuses on one such type of risk in the modern workplace
      psychosocial risks. The current study aimed to explore stakeholder perspectives,
      regarding the extent to which psychosocial risks are incorporated into strategic
      risk management practices, at both the business and policy level. METHODS: Semi
      structured interviews were conducted with 14 professionals, representing
      employer, expert, policy maker, and trade union stakeholder perspectives.
      RESULTS: It was found that the majority of organizations do not sufficiently, if
      at all, understand and incorporate psychosocial risks into strategic decision
      making, whereby the key barrier related to practical difficulties of not knowing
      how to manage psychosocial risks adequately. CONCLUSION: The study found that
      there is a need to close the gap between policy and practice on a number of
      levels. Future recommendations comprise a policy framework and infrastructure
      underpinned by educational initiatives, partnerships, and networks to drive a
      shift in attitudes toward recognizing the duality of the concept of risk
      (including both potential negative and positive outcomes) and moving beyond
      simple regulatory compliance.

PMID- 23961332
TI  - Work-related stress risk assessment in Italy: a methodological proposal adapted
      to regulatory guidelines.
AB  - BACKGROUND: Work-related stress is one of the major causes of occupational ill
      health. In line with the regulatory framework on occupational health and safety
      (OSH), adequate models for assessing and managing risk need to be identified so
      as to minimize the impact of this stress not only on workers' health, but also on
      productivity. METHODS: After close analysis of the Italian and European reference
      regulatory framework and work-related stress assessment and management models
      used in some European countries, we adopted the UK Health and Safety Executive's
      (HSE) Management Standards (MS) approach, adapting it to the Italian context in
      order to provide a suitable methodological proposal for Italy. RESULTS: We have
      developed a work-related stress risk assessment strategy, meeting regulatory
      requirements, now available on a specific web platform that includes software,
      tutorials, and other tools to assist companies in their assessments. CONCLUSION:
      This methodological proposal is new on the Italian work-related stress risk
      assessment scene. Besides providing an evaluation approach using scientifically
      validated instruments, it ensures the active participation of occupational health
      professionals in each company. The assessment tools provided enable companies not
      only to comply with the law, but also to contribute to a database for monitoring
      and assessment and give access to a reserved area for data analysis and
      comparisons.

PMID- 23961333
TI  - Biorisk assessment of medical diagnostic laboratories in Nigeria.
AB  - BACKGROUND: The aim of this study was to assess public and private medical
      diagnostic laboratories in Nigeria for the presence of biosafety equipment,
      devices, and measures. METHODS: A total of 80 diagnostic laboratories in
      biosafety level 3 were assessed for the presence of biosafety equipment, devices,
      and compliance rate with biosafety practices. A detailed questionnaire and
      checklist was used to obtain the relevant information from enlisted laboratories.
      RESULTS: The results showed the presence of an isolated unit for microbiological
      work, leak-proof working benches, self-closing doors, emergency exits, fire
      extinguisher(s), autoclaves, and hand washing sinks in 21.3%, 71.3%, 15.0%, 1.3%,
      11.3%, 82.5%, and 67.5%, respectively, of all laboratories surveyed. It was
      observed that public diagnostic laboratories were significantly more likely to
      have an isolated unit for microbiological work (p = 0.001), hand washing sink (p
      = 0.003), and an autoclave (p <= 0.001) than private ones. Routine use of hand
      gloves, biosafety cabinet, and a first aid box was observed in 35.0%, 20.0%, and
      2.5%, respectively, of all laboratories examined. Written standard operating
      procedures, biosafety manuals, and biohazard signs on door entrances were
      observed in 6.3%, 1.3%, and 3.8%, respectively, of all audited laboratories. No
      biosafety officer(s) or records of previous spills, or injuries and accidents,
      were observed in all diagnostic laboratories studied. CONCLUSION: In all
      laboratories (public and private) surveyed, marked deficiencies were observed in
      the area of administrative control responsible for implementing biosafety.
      Increased emphasis on provision of biosafety devices and compliance with standard
      codes of practices issued by relevant authorities is strongly advocated.

PMID- 23961334
TI  - The effect of lifting speed on cumulative and peak biomechanical loading for
      symmetric lifting tasks.
AB  - BACKGROUND: To determine the influence of lifting speed and type on peak and
      cumulative back compressive force (BCF) and shoulder moment (SM) loads during
      symmetric lifting. Another aim of the study was to compare static and dynamic
      lifting models. METHODS: Ten male participants performed a floor-to-shoulder,
      floor-to-waist, and waist-to-shoulder lift at three different speeds [slow (0.34
      m/s), medium (0.44 m/s), and fast (0.64 m/s)], and with two different loads
      [light (2.25 kg) and heavy (9 kg)]. Two-dimensional kinematics and kinetics were
      determined. A three-way repeated measures analysis of variance was used to
      calculate peak and cumulative loading of BCF and SM for light and heavy loads.
      RESULTS: Peak BCF was significantly different between slow and fast lifting
      speeds (p < 0.001), with a mean difference of 20% between fast and slow lifts.
      The cumulative loading of BCF and SM was significantly different between fast and
      slow lifting speeds (p < 0.001), with mean differences >=80%. CONCLUSION: Based
      on peak values, BCF is highest for fast speeds, but the BCF cumulative loading is
      highest for slow speeds, with the largest difference between fast and slow lifts.
      This may imply that a slow lifting speed is at least as hazardous as a fast
      lifting speed. It is important to consider the duration of lift when determining
      risks for back and shoulder injuries due to lifting and that peak values alone
      are likely not sufficient.

PMID- 23961335
TI  - The validity and reliability of the second korean working conditions survey.
AB  - BACKGROUND: The aim of this study was to evaluate the quality of the Second
      Korean Working Conditions Survey (KWCS), focusing on its validity and
      reliability. METHODS: The external validity was evaluated by the assessment of
      sampling procedures and the response rate, in order to investigate the
      representativeness of the sample. The content validity was evaluated by the
      assessment of the development of the questionnaire, and the consistency of
      questions for the selected construct. The test-retest method was used to evaluate
      the reliability by means of a phone call survey of 30% of the respondents, who
      were randomly selected. The respondents' satisfaction regarding the survey
      procedures and interview time were analyzed to evaluate the quality of survey
      data. RESULTS: The external validity was assured by an acceptable sampling
      procedure, rigid multi-stage stratified cluster random sampling. The content
      validity was also guaranteed by a reasonable procedure for the development of the
      questionnaire with a pretest. The internal consistency of the questions for work
      autonomy was maintained, with 0.738 of Cronbach's alpha. The response rate of 36%
      was lower than that of the European Working Conditions Survey (EWCS), with a
      contact rate of 66%, compared to 76% for the EWCS. The matching rates of the five
      retested questions were more than 98% reliable. CONCLUSION: The quality of the
      second KWCS was assured by the high external and content validity and
      reliability. The rigid sampling procedure and development of the questionnaire
      contributed to quality assurance. The high level of reliability may be guaranteed
      by the sophisticated field survey procedures and the development of a technical
      manual for interviewers. The technical strategies for a high response rate should
      be developed for future surveys.

PMID- 23961336
TI  - Asbestos and Asbestos-related Diseases in Vietnam: In reference to the
      International Labor Organization/World Health Organization National Asbestos
      Profile.
AB  - This paper describes progress on formulating a national asbestos profile for the
      country of Vietnam. The Center of Asbestos Resource, Vietnam, formulated a
      National Profile on Asbestos-related Occupational Health, with due reference to
      the International Labor Organization/World Health Organization National Asbestos
      Profile. The Center of Asbestos Resource was established by the Vietnamese Health
      Environment Management Agency and the National Institute of Labor Protection,
      with the support of the Australian Agency for International Development, as a
      coordinating point for asbestos-related issues in Vietnam. Under the National
      Profile on Asbestos-related Occupational Health framework, the Center of Asbestos
      Resource succeeded in compiling relevant information for 15 of the 18 designated
      items outlined in the International Labor Organization/World Health Organization
      National Asbestos Profile, some overlaps of the information items
      notwithstanding. Today, Vietnam continues to import and use an average of more
      than 60,000 metric tons of raw asbestos per year. Information on asbestos-related
      diseases is limited, but the country has begun to diagnose mesothelioma cases,
      with the technical cooperation of Japan. As it stands, the National Profile on
      Asbestos-related Occupational Health needs further work and updating. However, we
      envisage that the National Profile on Asbestos-related Occupational Health will
      ultimately facilitate the smooth transition to an asbestos-free Vietnam. 

PMID- 23961337
TI  - Two task-specific dystonias in one hand.
AB  - BACKGROUND: Dystonia is characterized by involuntary muscle contractions that
      lead to abnormal postures and/or repetitive movements. Task-specific dystonia
      only manifests during a specific activity. CASE REPORT: We report a case of a
      female with writer's cramp who developed a second task-specific hand dystonia
      (tremor and abnormal posturing of the hand while using a computer mouse) many
      years after the initial onset. DISCUSSION: This observation is in agreement with
      the concept that task-specific hand dystonia is induced by repetitive, skilled
      hand movements in those who have an intrinsic vulnerability towards developing
      "dystonic" motor programs.

PMID- 23961338
TI  - A Safer Formulation Concept for Flame-Generated Engineered Nanomaterials.
AB  - The likely success or failure of the nanotechnology industry depends on the
      environmental health and safety of engineered nanomaterials (ENMs). While efforts
      toward engineering safer ENMs are sparse, such efforts are considered crucial to
      the sustainability of the nanotech industry. A promising approach in this regard
      is to coat potentially toxic nanomaterials with a biologically inert layer of
      amorphous SiO2. Core-shell particles exhibit the surface properties of their
      amorphous SiO2 shell while maintaining specific functional properties of their
      core material. A major challenge in the development of functional core-shell
      particles is the design of scalable high-yield processes that can meet large
      scale industrial demand. Here, we present a safer formulation concept for flame
      generated ENMs based on a one-step, in flight SiO2 encapsulation process, which
      was recently introduced by the authors as a means for a scalable manufacturing of
      SiO2 coated ENMs. Firstly, the versatility of the SiO2-coating process is
      demonstrated by applying it to four ENMs (CeO2, ZnO, Fe2O3, Ag) marked by their
      prevalence in consumer products as well as their range in toxicity. The ENM
      dependent coating fundamentals are assessed and process parameters are optimized
      for each ENM investigated. The effects of the SiO2-coating on core material
      structure, composition and morphology, as well as the coating efficiency on each
      nanostructured material, are evaluated using state-of-the-art analytical methods
      (XRD, N2 adsorption, TEM, XPS, isopropanol chemisorption). Finally, the
      biological interactions of SiO2-coated vs. uncoated ENMs are evaluated using
      cellular bioassays, providing valuable evidence for reduced toxicity for the SiO2
      coated ENMs. Results indicate that the proposed 'safer by design' concept bears
      great promise for scaled-up application in industry in order to reduce the
      toxicological profile of ENMs for certain applications.

PMID- 23961339
TI  - Unified approach to growth and aging in biological, technical and biotechnical
      systems.
AB  - Complex systems, in many different scientific sectors, show coarse-grain
      properties with simple growth laws with respect to fundamental microscopic
      algorithms. We propose a classification scheme of growth laws which includes
      human aging, tumor (and/or tissue) growth, logistic and generalized logistic
      growth and the aging of technical devices. The proposed classification permits to
      evaluate the aging/failure of combined new bio-technical "manufactured products",
      where part of the system evolves in time according to biological-mortality laws
      and part according to technical device behaviors. Moreover it suggests a direct
      relation between the mortality leveling-off for humans and technical devices and
      the observed small cure probability for large tumors. 

PMID- 23961340
TI  - Root anoxia effects on physiology and emissions of volatile organic compounds
      (VOC) under short- and long-term inundation of trees from Amazonian floodplains.
AB  - Volatile organic compound (VOC) emissions are affected by a variety of biotic and
      abiotic factors such as light intensity, temperature, CO2 and drought. Another
      stress factor, usually overlooked but very important for the Amazon region, is
      flooding. We studied the exchange of VOCs in relation to CO2 exchange and
      transpiration of 8 common tree species from the Amazonian floodplain forest grown
      up from seeds using a dynamic enclosure system. Analysis of volatile organics was
      performed by PTR-MS fast online measurements. Our study confirmed emissions of
      ethanol and acetaldehyde at the beginning of root anoxia after inundation,
      especially in less anoxia adapted species such as Vatairea guianensis, but not
      for Hevea spruceana probably due to a better adapted metabolism. In contrast to
      short-term inundation, long-term flooding of the root system did not result in
      any emission of ethanol or/and acetaldehyde. Emission of other VOCs, such as
      isoprenoids, acetone, and methanol exhibited distinct behavior related to the
      origin (igapo or varzea type of floodplain) of the tree species. Also
      physiological activities exhibited different response patterns for trees from
      igapo or varzea. In general, isoprenoid emissions increased within the course of
      some days of short-term flooding. After a long period of waterlogging, VOC
      emissions decreased considerably, along with photosynthesis, transpiration and
      stomatal conductance. However, even under long-term testing conditions, two tree
      species did not show any significant decrease or increase in photosynthesis. In
      order to understand ecophysiological advantages of the different responses we
      need field investigations with adult tree species. 

PMID- 23961341
TI  - Three novel F8 mutations in sporadic haemophilia A cases.

PMID- 23961342
TI  - Development and initial evaluation of a smartphone application based on
      acceptance and commitment therapy.
AB  - BACKGROUND: An intervention, consisting of an ACT-based smartphone-application
      and a web-based psychoeducation, has been developed. The smartphone-application,
      together with the psychoeducation, aims to function as a self-help intervention
      for living consistently with one's values. The study is an exploratory
      investigation of this new smartphone-based tool. CASE DESCRIPTION: Primarily, the
      study aims at investigating a new field, providing a basis for generating
      hypotheses for further research. The first aim of this initial, exploratory study
      was to examine if this intervention had an effect on the variables of: valued
      actions, psychological flexibility, and life satisfaction as well as the states
      of depression, anxiety and stress, for a non-clinical sample of 11 Swedish Iphone
      users. This was made with a quasi-experimental pretest-posttest design without
      control group. The second aim was to investigate how the participants experienced
      the intervention, as measured by a qualitative questionnaire. DISCUSSION AND
      EVALUATION: The group analyses showed that the participants increased their
      valued action and psychological flexibility significantly during the
      intervention. Furthermore, value-based actions and psychological flexibility
      showed small effect sizes when comparing pretest and posttest score. However, the
      design of the study makes it impossible to draw any certain conclusions. The
      qualitative questionnaire showed a general positive experience of the
      intervention. CONCLUSIONS: The results from the present study indicated that the
      intervention should be studied further. The findings also generated a number of
      hypotheses that could be investigated in further research.

PMID- 23961343
TI  - A gating mechanism for border node assisted association of wireless personal area
      networks.
AB  - IEEE 802.15.4 based Wireless Personal Area Networks (WPANs) are envisioned to
      play a vital role in the application centric ubiquitous networks. In IEEE802.15.4
      networks, the use of non-interfering logical channels in multiple PANs, operating
      in a Personal Operating Space (POS) ensures to control the scope of PAN-directed
      broadcasts, reduce received energy per PAN device, and minimize interference at
      the physical layer. At the downside the inter-PAN communication is not possible
      with this setup as PANs in the same region remain unaware of each other's
      presence. This situation hinders sharing information of common interest amongst
      PANs and accessing infrastructure networks hopping through multiple PANs. In this
      paper, we present a comprehensive architecture enables neighboring PANs to
      communicate by diffusing into each other through border nodes. The basic idea is
      to time share logical channels to perform a gating operation by border nodes. Our
      contribution includes detection of border nodes, discovery of neighboring PAN(s),
      a common channel based gating protocol, interest diffusion and inter-PAN data
      transfer. We mathematically analyze the proposed architecture and carry out
      simulations in Network Simulator (ns2) for performance evaluation. Our
      simulations show that the proposed architecture gives optimal performance when
      multiple border nodes are able to perform gating. 

PMID- 23961344
TI  - Purification and characterization of a novel plant lectin from Pinellia ternata
      with antineoplastic activity.
AB  - A novel Pinellia ternata lectin was purified from the bulbs of a Chinese herb
      Pinellia ternata using a combination of hydrophobic chromatography and DEAE-ion
      exchange chromatography. The lectin was found to be a homodimer of 12093.3 Da
      subunits as determined by gel filtration and MS. Biochemical characterization of
      the lectin revealed the existence of a glycoprotein, which contains 3.22% neutral
      sugars. The N-terminal 10-amino acid sequence of the lectin, QGVNISGQVK, has not
      been reported for other lectins. The lectin had a special agglutinating activity
      with mouse erythrocytes at a minimum concentration of 8.0 ug/ml. The lectin was
      stable in the pH range of pH 5-12 and temperatures up to 80 degrees C for 30 min.
      The results of MTT experiment showed that the lectin had significant effect
      towards tumor cells, the maximum inhibition of cell proliferation with Sarcoma
      180, HeLa and K562 cell line were 85.2%, 74.6% and 59.4% respectively.
      Experimental therapy in vivo also showed that PTL apparently inhibited
      transplanted tumor in mice. Flow cytometric analysis demonstrated that PTL
      inhibited the proliferation of Sarcoma 180 in a time- and dose-dependent manner
      through inhibiting the transition of G1/S and subsequently inducing G0/G1 cell
      cycle arrest. Thus, Pinellia ternata lectin displays a high potential for
      antitumor activity. 

PMID- 23961345
TI  - A rugged, precise and accurate new gravimetry method for the determination of
      gold: an alternative to fire assay method.
AB  - A new, rugged, precise, accurate and fast primary method of measurement has been
      proposed for the determination of gold in various gold articles. Precise and
      accurate measurement of gold is the primary requirement for hall marking and to
      trade gold internationally, as billions of dollars of gold are trading world wide
      for the various applications. At present Fire Assay ASTM E 1335-08 is the only
      Standard Test Method for the determination of Gold, which is accepted
      internationally. But the method is time consuming, cumbersome and required
      expertise to perform the test. In the present investigation, a method has been
      developed gravimetry based on direct determination of gold after reducing gold in
      zero-valent state by hydroxylamine hydrochloride. Gravimetry is the most reliable
      technique and having highest metrological qualities in comparison to titremetry
      and instrumental method and the results of gravimetry are directly traceable to
      SI unit. The results of gravimetric method are accepted without reference to a
      standard of the same quantity. Several experiments were carried out with and
      without impurities and it has been concluded that gold can be determined
      accurately and precisely in presence of several impurities. Five replicates of
      approximate 0.2 g gold samples were analyzed following method proposed and
      percentage purity were found to be 99.993 +/- 0.0056 with 95% confidence level (k
      = 2). The combined uncertainty in gold measurement has also been evaluated using
      potential sources of the method according to the EURACHEM/GUM guidelines. 

PMID- 23961346
TI  - General Didactics and Instructional Design: eyes like twins A transatlantic
      dialogue about similarities and differences, about the past and the future of two
      sciences of learning and teaching.
AB  - Although General Didactics (GD) and Instructional Design (ID) have not shown many
      points of contact in the past, there are some obvious parellels from the
      perspective of their historical development. This will be examined in detail in
      this article. More specifically, we speak about model building, which has
      characterized General Didactics and Instructional Design for some decades.
      However, the models of General Didactics and Instructional Design are not problem
      free with regard to the continuity and advancement of both disciplines. First, we
      will describe the historical roots of both disciplines and examine which elements
      of theory are of central importance. Second, we will try to answer the question
      of which kind of model building could be considered as predominant and what
      problems result from this predominance. In order to do this, we will describe
      empirical studies on the use of instructional models and discuss these studies
      from the perspective of the philosophy of science. Third, we will draw inferences
      for future processes of model building in order to prevent the same problems that
      happened in the past from happening again. Finally, we will discuss the issue of
      what General Didactics can learn from Instructional Design and vice versa. 

PMID- 23961347
TI  - Calcium/calmodulin-dependent protein kinases in the carotid body: an
      immunohistochemical study.
AB  - We determined the presence of Ca(2+)/calmodulin-dependent protein kinases
      (CaMKs), a family of multifunctional proteins engaged in Ca(2+)-linked signaling,
      in carotid body chemoreceptor cells which are critical for the hypoxia-sensing.
      Carotid bodies were dissected from anesthetized normoxic adult Wistar rats and
      were double stained for individual CaMKs and for tyrosine hydroxylase (TH), a
      marker of chemoreceptor cells. Immunofluorescence was examined by confocal laser
      scanning microscopy. We found that CaMKI and CaMKII were expressed in
      chemoreceptor cells, but their distribution and intensity varied. CaMKI
      immunoreactivity was distributed throughout the cytoplasm, whereas that of CaMKII
      was localized in the cytoplasmic periphery of chemoreceptor cells. An overlap of
      CaMKI or CaMKII fluorescent probes with TH affirmed the presence of either
      protein in the chemoreceptor cells. CaMKIV could not be conclusively visualized
      by the used method. The study shows the expressions of CaMKI and CaMKII in
      chemoreceptor cells, which raises the plausibility of CaMKs' role in carotid body
      function. 

PMID- 23961348
TI  - Meiotic restitution mechanisms involved in the formation of 2n pollen in Agave
      tequilana Weber and Agave angustifolia Haw.
AB  - A cytological analysis of the microsporogenesis was carried out in the Agave
      tequilana and A. angustifolia species. Several abnormalities such as chromosomal
      bridges, lagging chromosomes, micronuclei, monads, dyads and triads were found.
      The morphological analysis of the pollen, together with the above-mentioned 2n
      microspores, allowed us to confirm the presence of 2n pollen as well as its
      frequency. In both A. tequilana and A. angustifolia two different mechanisms were
      observed: the first mechanism, a failure in the cytokinesis in meiosis II caused
      the formation of dyads with two 2n cells and triads containing two n cells and
      one 2n cell; the second mechanism, involves an abnormal spindle, which caused the
      formation of triads with two n cells and one 2n cell. Likewise, the presence of
      monads was detected in both species, these, might be caused by a failure of the
      cytokinesis in both meiotic divisions. This is the first report about the
      presence of a Second Division Restitution mechanism (SDR) which causes the
      formation of 2n pollen in the genus Agave. The genetic implications of the
      presence of 2n pollen in the genus Agave are discussed. 

PMID- 23961349
TI  - The antifungal effect of cellobiose lipid on the cells of Saccharomyces
      cerevisiae depends on carbon source.
AB  - The cellobiose lipid of Cryptococcus humicola, 16-(tetra-O-acetyl-beta
      cellobiosyloxy)-2-hydroxyhexadecanoic acid, is a natural fungicide. Sensitivity
      of the cells of Saccharomyces cerevisiae to the fungicide depends on a carbon
      source. Cellobiose lipid concentrations inducing the leakage of potassium ions
      and ATP were similar for the cells grown in the medium with glucose and ethanol.
      However, the cells grown on glucose and ethanol died at 0.05 mg ml(-1) and 0.2 mg
      ml(-1) cellobiose lipid, respectively. Inorganic polyphosphate (PolyP) synthesis
      was 65% of the control with 0.05 mg ml(-1) cellobiose lipid during cultivation on
      ethanol. PolyP synthesis was not observed during the cultivation on glucose at
      the same cellobiose lipid concentration. The content of longer-chain polyP was
      higher during cultivation on ethanol. We speculate the long-chained polyP
      participate in the viability restoring of ethanol-grown cells after treatment
      with the cellobiose lipid. 

PMID- 23961351
TI  - Evidence for conservation and sustainable use in a fragment of the Atlantic
      forest in southeastern Brazil by a traditional human group.
AB  - The use of forest resources by a rural community adjacent to a Biological Reserve
      was examined using quantitative methods based on the consensus of six local
      specialists. Plants with trunk diameters at 1.3 m above soil level (DBH) >= 5 cm
      were sampled in 0.5 ha of forest and their use-value (UV) were calculated and
      associated with their structural descriptors. A total of 129 species were
      identified, and 69 of them having known uses. The species with largest UV were:
      Xylopia sericea, Lecythis lanceolata and Guarea macrophylla. The results
      demonstrated that neither the degree of recognition of taxa by the local
      specialists nor their use-versatility depended on their abundance in nature. The
      results corroborate the hypothesis that richness of a plant family is a
      predictive character of its cultural importance and the community recognizes the
      value of conserving the forest remnants. 

PMID- 23961350
TI  - BRCA1 And BRCA2 analysis of Argentinean breast/ovarian cancer patients selected
      for age and family history highlights a role for novel mutations of putative
      south-American origin.
AB  - BACKGROUND: The spectrum of BRCA1/2 genetic variation in breast-ovarian cancer
      patients has been scarcely investigated outside Europe and North America, with
      few reports for South America, where Amerindian founder effects and recent
      multiracial immigration are predicted to result in high genetic diversity. We
      describe here the results of BRCA1/BRCA2 germline analysis in an Argentinean
      series of breast/ovarian cancer patients selected for young age at diagnosis or
      breast/ovarian cancer family history. METHODS: The study series (134 patients)
      included 37 cases diagnosed within 40 years of age and no family history (any
      ethnicity, fully-sequenced), and 97 cases with at least 2 affected relatives (any
      age), of which 57 were non-Ashkenazi (fully-sequenced) and 40 Ashkenazi (tested
      only for the founder mutations c.66_67delAG and c.5263insC in BRCA1 and
      c.5946delT in BRCA2). DISCUSSION: We found 24 deleterious mutations (BRCA1:16;
      BRCA2: 8) in 38/134 (28.3%) patients, of which 6/37 (16.2%) within the young age
      group, 15/57 (26.3%) within the non-Ahkenazi positive for family history; and
      17/40 (42.5%) within the Ashkenazi. Seven pathogenetic mutations were novel, five
      in BRCA1: c.1502_1505delAATT, c.2626_2627delAA c.2686delA, c.2728 C > T,
      c.3758_3759delCT, two in BRCA2: c.7105insA, c.793 + 1delG. We also detected 72
      variants of which 54 previously reported and 17 novel, 33 detected in an
      individual patient. Four missense variants of unknown clinical significance,
      identified in 5 patients, are predicted to affect protein function. While global
      and European variants contributed near 45% of the detected BRCA1/2 variation, the
      significant fraction of new variants (25/96, 26%) suggests the presence of a
      South American genetic component. This study, the first conducted in Argentinean
      patients, highlights a significant impact of novel BRCA1/2 mutations and genetic
      variants, which may be regarded as putatively South American, and confirms the
      important role of founder BRCA1 and BRCA2 mutations in Argentinean Ashkenazi
      Jews.

PMID- 23961352
TI  - Folate receptor alpha (FRA) expression in breast cancer: identification of a new
      molecular subtype and association with triple negative disease.
AB  - Given that several targeted therapies directed towards folate receptor alpha
      (FRA) are in late stage clinical development, the sensitive and robust detection
      of FRA in tissues is of paramount importance relative to patient selection,
      prognosis and prediction. In the present study we undertook an
      immunohistochemical evaluation of expression of FRA in breast cancer samples
      using formalin-fixed, paraffin-embedded (FFPE) tissues, primarily invasive ductal
      carcinomas, using a newly described monoclonal antibody, 26B3. Samples assessed
      included both tissue microarrays (TMA) and whole tissue sections from archival
      tissue blocks. Normal breast shows a highly restricted expression of FRA to
      luminal membrane staining of secretory ductal cells, consistent with FRA
      secretion into milk. In early stage (stages I-III) invasive ductal carcinomas,
      FRA staining was observed in approximately 30% of all samples, independent of
      molecular subtype (estrogen receptor (ER)/progesterone receptor (PR)/human
      epidermal growth factor receptor type 2 (Her2)). However, FRA expression was
      shown to associate with ER/PR negative tumors relative to ER/PR positive tumors
      (p = 0.012) and perhaps more importantly, with triple negative breast cancers
      (TNBC; p < 0.0001). FRA immunoreactivity was also shown to be retained in stage
      IV metastatic breast cancer samples from diverse anatomic sites including lymph
      node and bone. In metastatic breast cancer, FRA was shown to be expressed in 86%
      of TNBC patients. Taken together, these data suggest that FRA expressing breast
      cancer represents a novel molecular subtype and, further, may represent a new
      therapeutic target for this devastating disease. 

PMID- 23961353
TI  - Zoning for management in wetland nature reserves: a case study using Wuliangsuhai
      Nature Reserve, China.
AB  - BACKGROUND: Zoning is a fundamental tool for the effective management of nature
      reserves. A three-zone model (core zone, buffer zone, and experimental zone) has
      been applied to nature reserves in China since 1980s; however, this model appears
      not fit for all types of nature reserves, especially wetlands. CASE DESCRIPTION:
      Wuliangsuhai is such a typical wetland reserve, which can represent most of the
      other wetland reserves in China, for both its human utilization, and for its
      function as the bird habitat. The "Component-Process-Service" (CPS) framework of
      the Convention on Wetlands allows a determination of the "ecological character"
      of the wetland and also allows identification of potential threats, providing
      thus a perspective for management opportunities and challenges. DISCUSSION AND
      EVALUATION: Applying the CPS framework to Wuliangsuhai wetland nature reserve, we
      have had a better understanding of the ecosystem services and its relationship
      with the ecological process and components of the wetland. A comparison of
      effectiveness in maintaining ecosystem services by the two zoning models (the
      existing three-zone model, and the new zoning model) was made. CONCLUSIONS: The
      study suggested introducing an additional risk-control zone to be more effective
      in managing and alleviating threats to the ecological character than the standard
      3-zone system. Furthermore, a "dynamic" zoning that takes into account the annual
      variation in habitat and avifauna distribution, as an elaboration of the Four
      zone structure, may achieve the desired conservation objectives in an even more
      effective manner. The proposed zonation structure has the added benefit of
      promoting harmonization between nature conservation and local sustainable
      development.

PMID- 23961354
TI  - Breast cancer patients' recall of receiving patient assistance services.
AB  - BACKGROUND: The objective of this study was to assess factors that affect breast
      cancer patients' recall of patient assistance services. METHODS: We surveyed
      newly-diagnosed breast cancer patients and compared recall of receiving patient
      assistance services at 2 weeks and 6 months in a patient-assistance randomized
      controlled trial aimed to connect women to such programs. The intervention group
      received information about assistance programs targeted to their practical,
      psychosocial, and/or informational needs; the control group received a Department
      of Health pamphlet about breast cancer and its treatment, including a list of
      patient assistance services. FINDINGS: Of 333 women, 210 (63%) reported
      informational, 183 (55%) psychosocial and 177 (53%) practical needs. At 2 weeks,
      96% (202/210) of women with informational needs reported receiving informational
      material but at 6 months, recall dropped to 69% (140/210). All women whose
      informational needs were met recalled receiving information, compared to 31%
      whose needs were unmet (p < 0.0001). Of 109 intervention patients with
      psychosocial or practical needs, 77% (79) contacted a program specified in their
      action plan at 2 weeks. However, at 6 months, only 39% (31/79) recalled
      contacting a program. Women without recall were less likely to report having
      their needs met (6% vs. 58%; p < 0.001). CONCLUSIONS: Recall of patient
      assistance services is strongly related to having needs met. Use of patient
      surveys to evaluate utilization or impact of such programs should be used with
      caution due to poor patient recall. CLINICAL TRIALS # NCT00233077:
      http://www.clinicaltrials.gov/ct2/show/NCT00233077?term=Nina+Bickell&rank=2.

PMID- 23961355
TI  - Contributions of vulnerable hydrogeomorphic habitats to endemic plant diversity
      on the Kas Plateau, Western Ghats.
AB  - BACKGROUND: The Western Ghats of India are known to be a major biological hotspot
      that supports plant diversity and endemism. On the Kas Plateau, a lateritic
      plateau of the northern Western Ghats, we examined mesoscale distributions of
      endemic, rare, or locally significant plant species in forest habitats or on the
      plateau and its escarpments, and assessed the edaphic and hydrological parameters
      of seasonal plateau microhabitats. FINDINGS: Almost two thirds of over 100
      phytogeographically significant species occur on the plateau top; these represent
      26 plant families and 43 genera. About 80% of the species are restricted to the
      upper plateau and its escarpments. CONCLUSION: Since botanically critical plateau
      habitats are generally small, dependent on seasonal monsoon moisture, and
      determined by drainage-related parameters that can be altered by anthropogenic
      activities, they are highly vulnerable. Maintenance of appropriate microhabitats
      should be a key consideration for conservation of regionally significant plant
      biota.

PMID- 23961356
TI  - Microbial diversity of vermicompost bacteria that exhibit useful agricultural
      traits and waste management potential.
AB  - Vermicomposting is a non-thermophilic, boioxidative process that involves
      earthworms and associated microbes. This biological organic waste decomposition
      process yields the biofertilizer namely the vermicompost. Vermicompost is a
      finely divided, peat like material with high porosity, good aeration, drainage,
      water holding capacity, microbial activity, excellent nutrient status and
      buffering capacity thereby resulting the required physiochemical characters
      congenial for soil fertility and plant growth. Vermicompost enhances soil
      biodiversity by promoting the beneficial microbes which inturn enhances plant
      growth directly by production of plant growth-regulating hormones and enzymes and
      indirectly by controlling plant pathogens, nematodes and other pests, thereby
      enhancing plant health and minimizing the yield loss. Due to its innate
      biological, biochemical and physiochemical properties, vermicompost may be used
      to promote sustainable agriculture and also for the safe management of
      agricultural, industrial, domestic and hospital wastes which may otherwise pose
      serious threat to life and environment. 

PMID- 23961357
TI  - Isolation of a novel strain of Candida shehatae for ethanol production at
      elevated temperature.
AB  - Considering the cost-effectiveness of bioethanol production, there is a need for
      a yeast strain which can convert glucose and xylose into ethanol at elevated
      temperatures. We succeeded in isolating a yeast strain, designated strain ATY839,
      which was capable of ethanolic fermentation at temperatures above those
      previously reported for yeasts able to ferment both glucose and xylose. Strain
      ATY839 was capable of producing a substantial amount of ethanol at up to 37
      degrees C from 2% glucose or 2% xylose. The results of a phylogenetic analysis
      suggest that strain ATY839 belongs to Candida shehatae. In additional, ethanol
      production from rice straw by strain ATY839 was examined. Compared with the
      control strains (Saccharomyces cerevisiae NBRC 0224, Scheffersomyces stipitis
      NBRC 10063, and C. shehatae ATCC 22984), strain ATY839 produced more ethanol in
      SSF even at 37 degrees C. The theoretical maximum yield of strain ATY839 was
      71.6% at 24 h. Thus, strain ATY839 is considered to be the most tolerant to high
      temperature of the C. shehatae strains. 

PMID- 23961358
TI  - Marketing technology in macroeconomics.
AB  - In this paper, we incorporate a marketing technology into a dynamic stochastic
      general equilibrium model by assuming a matching friction for consumption. An
      improvement in matching can be interpreted as an increase in matching technology,
      which we call marketing technology because of similar properties. Using a
      simulation analysis, we confirm that a positive matching technology shock can
      increase output and consumption. 

PMID- 23961359
TI  - Expression of human papillomavirus 6b L1 protein in silkworm larvae and enhanced
      green fluorescent protein displaying on its virus-like particles.
AB  - Human papillomavirus (HPV) 6b L1 capsid protein was expressed using the Bombyx
      mori nucleopolyhedrovirus (BmNPV) bacmid expression system in silkworm larvae.
      Two constructs, full-length L1 (500 a.a) and C-terminal-deleted short L1 (479
      a.a), and three PCR-manipulated antigenic loops at amino acids 55-56, 174-175,
      and 348-349 regions were incorporated with whole enhanced green fluorescent
      protein (EGFP). Expressed in full, short L1 proteins and variants were purified
      in heparin affinity column chromatography and confirmed by SDS-PAGE and western
      blot. The presence of self-assembled virus-like particles (VLPs) and EGFP
      incorporation on the surface of VLPs were confirmed by the observation of
      transmission electron and immunoelectron microscopies, respectively. HPV 6b L1
      major capsid protein was successfully expressed in silkworm, and effective
      manipulation on the antigenic regions showed the path to versatile vaccine
      development based on HPV L1-VLPs. 

PMID- 23961360
TI  - Finding the undiscovered roles of genes: an approach using mutual ranking of
      coexpressed genes and promoter architecture-case study: dual roles of thaumatin
      like proteins in biotic and abiotic stresses.
AB  - Regarding the possible multiple functions of a specific gene, finding the
      alternative roles of genes is a major challenge. Huge amount of available
      expression data and the central role of the promoter and its regulatory elements
      provide unique opportunely to address this issue. The question is that how the
      expression data and promoter analysis can be applied to uncover the different
      functions of a gene. A computational approach has been presented here by analysis
      of promoter regulatory elements, coexpressed gene as well as protein domain and
      prosite analysis. We applied our approach on Thaumatin like protein (TLP) as
      example. TLP is of group 5 of pathogenesis related proteins which their
      antifungal role has been proved previously. In contrast, Osmotin like proteins
      (OLPs) are basic form of TLPs with proved role only in abiotic stresses. We
      demonstrated the possible outstanding homolouges involving in both biotic and
      abiotic stresses by analyzing 300 coexpressed genes for each Arabidopsis TLP and
      OLP in biotic, abiotic, hormone, and light microarray experiments based on mutual
      ranking. In addition, promoter analysis was employed to detect transcription
      factor binding sites (TFBs) and their differences between OLPs and TLPs. A
      specific combination of five TFBs was found in all TLPs presenting the key
      structure in functional response of TLP to fungal stress. Interestingly, we found
      the fungal response TFBs in some of salt responsive OLPs, indicating the possible
      role of OLPs in biotic stresses. Thirteen TFBS were unique for all OLPs and some
      found in TLPs, proposing the possible role of these TLPs in abiotic stresses.
      Multivariate analysis showed the possibility of estimating models for
      distinguishing biotic and abiotic functions of TIPs based on promoter regulatory
      elements. This is the first report in identifying multiple roles of TLPs and OLPs
      in biotic and abiotic stresses. This study provides valuable clues for screening
      and discovering new genes with possible roles in tolerance against both biotic
      and abiotic stresses. Interestingly, principle component analysis showed that
      promoter regulatory elements of TLPs and OLPs are more variable than protein
      properties reinforcing the prominent role of promoter architecture in determining
      gene function alteration. 

PMID- 23961361
TI  - Kinetics of improved 1,4-alpha-D-glucan glucohydrolase biosynthesis from a newly
      isolated Aspergillus oryzae IIB-6 and parameter significance analysis by 2
      factorial design.
AB  - Sixteen different mould cultures viz. Aspergillus, Alternaria, Arthroderma,
      Trichoderma, Fusarium, Penicillium, Rhizopus and Chochliobolus were isolated from
      the soil samples of Qatar by serial dilution method. The preliminary screening of
      isolates was done by selecting initial colonies showing relatively bigger zones
      of starch hydrolysis on nutrient agar plates. The isolates were then subjected to
      secondary screening by submerged fermentation (SmF). The 1,4-alpha-D-glucan
      glucohydrolase (GGH) activity ranged from 1.906-12.675 U/ml/min. The product
      yield was analysed in dependence of mycelial morphology, biomass level and
      protein content. The isolate Aspergillus oryzae llB-6 which gave maximum enzyme
      production was incubated in M3 medium containing 20 g/l starch, 10 g/l lactose,
      8.5 g/l yeast extract, 6 g/l corn steep liquor (CSL), 1.2 g/l MgSO4.7H2O, 1.3 g/l
      NH4Cl, 0.6 g/l CaCl2.2H2O, pH 5 at 30+/-2 degrees C and 200 rpm. On the basis of
      kinetic variables, notably Qp (0.058+/-0.01(a) U/g/h), Yp/s (0.308+/-0.03(ab)
      U/g) and qp (0.210+/-0.032(abc) U/g fungal biomass/h), A. oryzae IIB-6 was found
      to be a hyper producer of GGH (LSD 0.0345) compared to A. kawachii IIB-2. A
      noticeable enhancement in enzyme activity of over 30% was observed (13.917+/-1.01
      U/ml/min) when the process parameters viz. cultural conditions (pH 5, incubation
      period 72 h) and nutritional requirements (6 g/l CSL, 9.5 g/l yeast extract, 10
      g/l starch, 20 g/l lactose) were further optimized using a 2-factorial Plackett
      Burman design. The model terms were found to be highly significant (HS, p<=0.05),
      indicating the potential utility of the culture (dof~3). 

PMID- 23961362
TI  - Biochemical modulation of growth, lipid quality and productivity in mixotrophic
      cultures of Chlorella sorokiniana.
AB  - The genus Chlorella is a widely employed microalga for biodiesel, as it can be
      grown using photo/mixo/heterotrophic mode of cultivation. The present
      investigation was undertaken with the hypothesis that addition of different
      substrates (amino acids, carbon sources, vitamins) along with reducing agents may
      aid in diverting Acetyl CoA to malonyl CoA or fatty acid biosynthesis, under
      mixotrophic conditions in Chlorella sorokiniana. Preliminary investigations
      undertaken with two reducing agents individually (sodium thiosulphate and methyl
      viologen) along with selected substrates revealed the promise of sodium
      thiosulphate (1%) in enhancing lipid accumulation significantly. Further, the
      role of inclusion of twelve substrates and sodium thiosulphate revealed that
      supplementation with tryptophan (0.1%) recorded 57.28% enhancement in lipid
      productivity on 4(th) day. Highest values of lipid productivity of 33% were
      recorded on 8(th) day in 0.1% glucose supplemented medium containing sodium
      thiosulphate. Fatty Acid Methyl Ester (FAME) profiles generated revealed
      significant reduction in the content of Poly unsaturated fatty acids (PUFA) and
      enhanced Mono unsaturated fatty acids (MUFA) (especially oleic acid) in the
      treatments involving tryptophan, Vitamin B12, sodium pyruvate and glucose. This
      study reveals the promise of using sodium thiosulphate along with selected
      substrate for enriching the quality and quantity of lipids, which can be valuable
      for exploiting algae as a source of biodiesel. 

PMID- 23961363
TI  - Prevalence of poor and rapid metabolizers of drugs metabolized by CYP2B6 in North
      Indian population residing in Indian national capital territory.
AB  - Identification of poor and rapid metabolizers for the category of drugs
      metabolized by cytochrome P450 2B6 (CYP2B6) is important for understanding the
      differences in clinical responses of drugs metabolized by this enzyme. This study
      reports the prevalence of poor and rapid metabolizers in North Indian population
      residing in the National Capital Territory. The prevalence of poor and rapid
      metabolizers was determined in the target population for the category of drugs
      metabolized by CYP2B6 by measuring plasma bupropion, a drug metabolized by
      CYP2B6, and its metabolite. Bupropion (75 mg) was administered to 107 volunteers,
      and the drug (bupropion) and its metabolite (hydroxybupropion) were determined
      simultaneously by LCMS/MS in the plasma. CYP2B6 activity was measured as
      hydroxybupropion/bupropion ratio, and volunteers were categorized as rapid or
      poor metabolizers on the basis of cutoff value of log
      (hydroxybupropion/bupropion). Significant differences were observed between the
      mean metabolite/drug ratio of rapid metabolizers (Mean = 0.59) and poor
      metabolizers (Mean = 0.26) with p<0.0001. Results indicate that 20.56%
      individuals in the target population were poor metabolizers for the category of
      drugs metabolized by CYP2B6. Cutoff value defined in this study can be used as a
      tool for evaluating the status of CYP2B6 using bupropion as a probe drug. The
      baseline information would be clinically useful before administering the drugs
      metabolized by this isoform. 

PMID- 23961364
TI  - Presence of chelonid fibropapilloma-associated herpesvirus in tumored and non
      tumored green turtles, as detected by polymerase chain reaction, in endemic and
      non-endemic aggregations, Puerto Rico.
AB  - Fibropapillomatosis (FP), a transmissible neoplastic disease of marine turtles
      characterized by a likely herpesviral primary etiology, has emerged as an
      important disease in green sea turtles (Chelonia mydas) over the past three
      decades. The objectives of this study were to determine the suitability of three
      different chelonid fibropapilloma-associated herpesvirus (CFPHV) gene targets in
      polymerase chain reaction (PCR) assays of affected tissues; to explore the
      presence of CFPHV in non-affected skin from turtles with and without tumors; and
      to better understand tissue localization of the CFPHV genome in a tumor-free
      turtle by evaluating CFPHV presence in microanatomic tissue sites. Two
      aggregations of green sea turtles (Chelonia mydas) in Puerto Rico were evaluated,
      with six sampling intervals over the three-year period 2004-2007. Primary and
      nested PCR for three different herpesviral gene targets- DNA polymerase, capsid
      maturation protease, and membrane glycoprotein B- were performed on 201 skin
      biopsies taken from 126 turtles with and without external tumors. Laser capture
      microdissection and nested PCR were used to identify tissue localizations of
      CFPHV in skin from a normal turtle. Of the turtles sampled in Manglar Bay, 30.5%
      had tumors; at the relatively more pristine Culebrita, 5.3% of turtles sampled
      had tumors. All three PCR primer combinations successfully amplified CFPHV from
      tumors, and from normal skin of both tumored and tumor-free turtles. Via nested
      PCR, the polymerase gene target proved superior to the other two gene targets in
      the positive detection of CFPHV DNA. CFPHV infection may be common relative to
      disease incidence, supporting the idea that extrinsic and/or host factors could
      play a transforming role in tumor expression. Laser capture microdissection
      revealed CFPHV in skin from a tumor-free turtle, harbored in both epidermal and
      dermal tissues. Identification of CFPHV harbored in a non-epidermal site (dermis)
      of a tumor-free turtle indicates that virus is latent in a non-tumored host. 

PMID- 23961365
TI  - A BCL2 promoter polymorphism rs2279115 is not associated with BCL2 protein
      expression or patient survival in breast cancer patients.
AB  - The B-cell CLL/lymphoma 2 (BCL2) gene family encodes pro- and anti-apoptotic
      proteins that are critical regulators of programmed cell death. Higher levels of
      BCL2 expression in breast tumours have been shown to be an independent prognostic
      factor for improved survival from breast cancer. The promoter single nucleotide
      polymorphism (SNP) rs2279115 has been associated with both BCL2 expression and
      patient survival. The aim of this study was to attempt to replicate these
      observations in a cohort of 1015 UK women with breast cancer, and to compare
      genotype frequencies in cases and controls. In this study, 1015 breast cancer
      cases and 1034 control subjects were genotyped for the rs2279115 SNP by 5'
      nuclease PCR. Paraffin embedded tumour tissue for 342 case subjects was assembled
      into tissue microarrays, and the level of expression of BCL2 was established by
      immunohistochemistry. Kaplan Meier survival curves and Cox Proportional Hazards
      models were used to examine the effect of genotype on patient survival. The
      effect of SNP genotype on tumour BCL2 protein levels and breast cancer
      susceptibility was assessed by logistic regression. In this study higher BCL2
      expression was significantly associated with improved survival from breast cancer
      (p = 0.015), in keeping with previous reports. The SNP rs2279115 was not found to
      be associated with tumour expression of BCL2, (p = 0.77), and neither was it
      associated with case/control status (p = 0.25). There was no significant
      association between the SNP and overall survival (p = 0.75). In conclusion, we
      found that higher tumour BCL2 expression is associated with improved survival
      from breast cancer, in keeping with previous studies. However, in contrast to a
      previous report, the promoter SNP rs2279115 was not associated with BCL2
      expression or overall survival from breast cancer. 

PMID- 23961366
TI  - Tracing contacts of TB patients in Malaysia: costs and practicality.
AB  - Tuberculin skin testing (TST) and chest X-ray are the conventional methods used
      for tracing suspected tuberculosis (TB) patients. The purpose of the study was to
      calculate the cost incurred by Penang General Hospital on performing one contact
      tracing procedure using an activity based costing approach. Contact tracing
      records (including the demographic profile of contacts and outcome of the contact
      tracing procedure) from March 2010 until February 2011 were retrospectively
      obtained from the TB contact tracing record book. The human resource cost was
      calculated by multiplying the mean time spent (in minutes) by employees doing a
      specific activity by their per-minute salaries. The costs of consumables,
      Purified Protein Derivative vials and clinical equipment were obtained from the
      procurement section of the Pharmacy and Radiology Departments. The cost of the
      building was calculated by multiplying the area of space used by the facility
      with the unit cost of the public building department. Straight-line deprecation
      with a discount rate of 3% was assumed for the calculation of equivalent annual
      costs for the building and machines. Out of 1024 contact tracing procedures, TST
      was positive (>=10 mm) in 38 suspects. However, chemoprophylaxis was started in
      none. Yield of contact tracing (active tuberculosis) was as low as 0.5%. The
      total unit cost of chest X-ray and TST was MYR 9.23 (2.90 USD) & MYR 11.80 (USD
      3.70), respectively. The total cost incurred on a single contact tracing
      procedure was MYR 21.03 (USD 6.60). Our findings suggest that the yield of
      contact tracing was very low which may be attributed to an inappropriate
      prioritization process. TST may be replaced with more accurate and specific
      methods (interferon gamma release assay) in highly prioritized contacts; or TST
      positive contacts should be administered 6H therapy (provided that the chest
      radiography excludes TB) in accordance with standard protocols. The unit cost of
      contact tracing can be significantly reduced if radiological examination is done
      only in TST or IRGA positive contacts. 

PMID- 23961367
TI  - An approach to predict the risk of glaucoma development by integrating different
      attribute data.
AB  - Primary open-angle glaucoma (POAG) is one of the major causes of blindness
      worldwide and considered to be influenced by inherited and environmental factors.
      Recently, we demonstrated a genome-wide association study for the susceptibility
      to POAG by comparing patients and controls. In addition, the serum cytokine
      levels, which are affected by environmental and postnatal factors, could be also
      obtained in patients as well as in controls, simultaneously. Here, in order to
      predict the effective diagnosis of POAG, we developed an "integration approach"
      using different attribute data which were integrated simply with several machine
      learning methods and random sampling. Two data sets were prepared for this study.
      The one is the "training data set", which consisted of 42 POAG and 42 controls.
      The other is the "test data set" consisted of 73 POAG and 52 controls. We first
      examined for genotype and cytokine data using the training data set with general
      machine learning methods. After the integration approach was applied, we obtained
      the stable accuracy, using the support vector machine method with the radial
      basis function. Although our approach was based on well-known machine learning
      methods and a simple process, we demonstrated that the integration with two kinds
      of attributes, genotype and cytokines, was effective and helpful in diagnostic
      prediction of POAG. 

PMID- 23961368
TI  - Efficient production of polymer-grade L-lactic acid from corn stover hydrolyzate
      by thermophilic Bacillus sp. strain XZL4.
AB  - Lactic acid has been identified as one of the top 30 potential building-block
      chemicals from biomass. Therefore, the search for cheap raw materials is an
      objective to reduce the production costs. Efficient polymer-grade L-lactic acid
      production was achieved in this report by a thermophilic strain Bacillus sp. XZL4
      using corn stover hydrolyzate as sole carbon source. High L-lactic acid
      concentration (81.0 g L(-1)) was obtained from 162.5 g L(-1) concentrated corn
      stover hydrolyzate (total reducing sugar of 83.0 g L(-1)) with a volumetric
      productivity of 1.86 g L(-1) h(-1) (0-36 h) and a product yield of 0.98 g g(-1)
      total reducing sugars. This is the highest L-lactic acid concentration and yield
      reported from corn stover hydrolyzate. And the high optical purity of L-lactic
      acid obtained in this study also indicated that Bacillus sp. XZL4 is a promising
      polymer-grade L-lactic-acid producer from cellulosic biomass. 

PMID- 23961370
TI  - Triggers of migraine in children at a public hospital in India.
AB  - We conducted a descriptive study of children presenting with recurrent headaches
      to the general pediatric services of a tertiary-care, public hospital in northern
      India. This paper reports on the triggering factors of migraine in this
      population. 43 children, 3-18 year old (23 females, median age 10 years),
      presenting with recurrent headache from April, 2011 to January, 2012, were
      enrolled. History, clinical examination and follow-up were done using a
      structured proforma. Headache diagnosis was made on the basis of International
      Classification of Headache Disorders, 2nd edition (ICHD-II). 26 patients (60.5%)
      had headache with migraine features (11 had Tension type headache and 4 had non
      specific headaches). Stress (both physical and emotional) was identified by the
      majority of children (46.1%) as the trigger for the headache. The triggers
      reported were different from those reported from other settings in India. We wish
      to highlight that the relative contribution of triggers in pediatric migraine may
      not be similar across regions/populations. 

PMID- 23961369
TI  - Transdifferentiation of MALME-3M and MCF-7 Cells toward Adipocyte-like Cells is
      Dependent on Clathrin-mediated Endocytosis.
AB  - Enforced cell transdifferentiation of human cancer cells is a promising
      alternative to conventional chemotherapy. We previously identified albumin
      associated lipid- and, more specifically, saturated fatty acid-induced
      transdifferentiation programs in human cancer cells (HCCLs). In this study, we
      further characterized the adipocyte-like cells, resulting from the
      transdifferentiation of human cancer cell lines MCF-7 and MALME-3M, and proposed
      a common mechanistic approach for these transdifferentiating programs. We showed
      the loss of pigmentation in MALME-3M cells treated with albumin-associated
      lipids, based on electron microscopic analysis, and the overexpression of
      perilipin 2 (PLIN2) by western blotting in MALME-3M and MCF-7 cells treated with
      unsaturated fatty acids. Comparing the gene expression profiles of naive melanoma
      MALME-3M cells and albumin-associated lipid-treated cells, based on RNA
      sequencing, we confirmed the transcriptional upregulation of some key adipogenic
      gene markers and also an alternative splicing of the adipogenic master regulator
      PPARG, that is probably related to the reported up regulated expression of the
      protein. Most importantly, these results also showed the upregulation of genes
      responsible for Clathrin (CLTC) and other adaptor-related proteins. An increase
      in CLTC expression in the transdifferentiated cells was confirmed by western
      blotting. Inactivation of CLTC by chlorpromazine (CHP), an inhibitor of CTLC
      mediated endocytosis (CME), and gene silencing by siRNAs, partially reversed the
      accumulation of neutral lipids observed in the transdifferentiated cells. These
      findings give a deeper insight into the phenotypic changes observed in HCCL to
      adipocyte-like transdifferentiation and point towards CME as a key pathway in
      distinct transdifferentiation programs. DISCLOSURES: Simon C and Aguilar-Gallardo
      C are co-inventors of the International Patent Application No. PCT/EP2011/004941
      entitled "Methods for tumor treatment and adipogenesis differentiation".

PMID- 23961371
TI  - Acute exercise exacerbates ischemia-induced diastolic rigor in hypertensive
      myocardium.
AB  - Previous studies have shown that acute exercise preconditions the myocardium from
      ischemic injury. The purpose of this study was to test whether acute exercise
      protects the hypertensive myocardium from ischemia-induced diastolic rigor, and
      to compare the response between normotensive and uncompensated hypertensive
      hearts. Hearts harvested from female Wistar-Kyoto (WKY; n = 24) and spontaneously
      hypertensive rats (SHR; n = 27) (age:10-12 weeks) were exposed to ischemia
      (Langendorff isovolumic preparation; 22 minutes of no flow ischemia and studied
      following prior conditions of: 1) no exercise (WKY-CON, n=8; SHR-CON, n=8); 2)
      ischemia initiated one hour post-acute exercise (WKY-1HR, n = 8; SHR-1HR, n =
      11); and 3) ischemia initiated 24 hours post-acute exercise (WKY-24HR; n = 8; SHR
      24HR, n = 8). Acute exercise consisted of one bout of treadmill running at 25
      m/min for 60 minutes. Heart weight was similar between WKY and SHR despite
      elevated in vivo resting systolic blood pressure and rate pressure product in SHR
      (P<0.05). During normoxic perfusion, left ventricular (LV) Langendorff
      performance was similar between WKY and SHR over the post-exercise time course.
      However, during ischemia, LV diastolic rigor was less in WKY vs. SHR (P<0.05).
      Acute exercise augmented ischemia-induced LV dysfunction one hour post-exercise
      in SHR (P<0.05), with gradual recovery by 24 hours post-exercise. These data
      suggest that acute exercise promotes ischemic diastolic rigor in SHR, even prior
      to the development of cardiac hypertrophy. 

PMID- 23961372
TI  - Allozyme variability in populations of trout (Salmo trutta) from the rivers of
      Russia and Iran.
AB  - For the first time, an analysis was carried out of allozyme variability in trout
      (Salmo trutta) from three rivers of Iran. We studied 23 gene loci coding enzymes:
      glycerol-3-phosphate dehydrogenase (G3PDH), aspartate aminotransferase (AAT),
      malate dehydrogenase (MDH), lactate dehydrogenase (LDH), creatine kinase (CK),
      malic enzyme [NADP-dependent MDH] (MEP), superoxide dismutase (SOD), esterase
      (EST), and esterase D (EST-D). The obtained data demonstrate the similarity
      between the trout samples from different rivers of Iran according to genetic
      characteristics. Taking into account the differences by allozyme markers of
      allele frequencies and allele composition of some loci, we should expect that
      Iranian trout diverges significantly in genetics from the other trout populations
      of the Caspian Sea. 

PMID- 23961373
TI  - Production of the Bacillus licheniformis SubC protease using Lactococcus lactis
      NICE expression system.
AB  - In this work the subC gene from Bacillus licheniformis encoding subtilisin was
      cloned into the nisin-controlled expression (NICE) vectors (pNZ8048 and pNZ8148)
      with or without the signal peptide SP Usp45 directing extracellular secretion via
      Sec machinery. Extracellular protease production and activity was tested using
      Lactococcus lactis NZ9000 as host, which could be used for rennet production. The
      efficiency of protein production was tested using purified nisin and the
      supernatant of L. lactis NZ970 nisin producer. Similar results were obtained for
      1 ng/ml nisin and 10 000 diluted supernatant. SP Usp45 signal peptide effectively
      directed extracellular localization of active and stable protease. SubC signal
      for extracellular localization in B. licheniformis, was also recognized by L.
      lactis Sec pathway, although with lower efficiency, as shown by a 3-fold lower
      protease activity in the medium. Protease production and activity was optimized
      using parameters such as induction time, nutrients (glucose, casitone)
      supplementation during growth or protease stabilization by calcium ions. The
      results were also verified in fed-batch bioreactor for further scale-up of the
      expression system. 

PMID- 23961374
TI  - Alteration of non-protein respiratory quotient after hepatocellular carcinoma
      treatment can be related to des-gamma-carboxy prothrombin before treatment.
AB  - BACKGROUND: Transcatheter arterial chemoembolization (TACE) is an effective
      treatment for hepatocellular carcinoma (HCC) that would occasionally lead to
      energy malnutrition through therapeutic hypoxic stress. We aimed to clarify the
      correlation between the energy malnutrition after TACE and low tolerability for
      hypoxia of non-tumoral liver before TACE. FINDINGS: We performed a prospective
      cohort study involving 100 HCC patients who underwent TACE at Kobe University
      Hospital. Indirect calorimetry was performed before and 7 days after TACE, and
      non-protein respiratory quotient (npRQ) as an indicator of the energy
      malnutrition was measured. Blood biochemical examinations were also performed
      before TACE. As an indicator of hypoxic marker, des-gamma-carboxy prothrombin
      (DCP) was measured before TACE. The correlation between npRQ ratio (7 days
      after/before TACE) and DCP (before TACE) was statistically examined. Spearman's
      correlation coefficient test showed that npRQ ratio (Day 7/Day 0) was
      significantly related to DCP (Day 0) (p=0.0481, r=-0.2033). On the other hand,
      npRQ ratio (Day 7/Day 0) was not related to alpha fetoprotein (Day 0) (p=0.6254,
      r=-0.0494). CONCLUSIONS: The npRQ reduction after TACE was related to a high
      value of DCP before TACE. The energy malnutrition after TACE would originate from
      low tolerability for hypoxia of non-tumoral liver. The HCC patients with a high
      value of DCP before TACE would clinically have a high risk of the energy
      malnutrition after TACE.

PMID- 23961375
TI  - Cow dung: a potential biomass substrate for the production of detergent-stable
      dehairing protease by alkaliphilic Bacillus subtilis strain VV.
AB  - Cow dung, a cheap and easily available source of energy, was used as the
      substrate for the production of alkaline protease by solid-state fermentation
      using the Bacillus subtilis strain VV. In order to achieve the maximum yield of
      this enzyme, the following optimum process parameters are needed: fermentation
      period (72 h), pH (10.0), moisture content (140%), inoculum (25%), temperature
      (30-40 degrees C), carbon source (2% (w/w) maltose) and nitrogen source (1% (w/w)
      urea). The protease was stable over a broad temperature range (30-50 degrees C)
      and pH (8.0-10.0), with maximum activity at 50 degrees C and pH 10.0. Among the
      divalent ions tested, Ca(2+) (0.01 M) increased enzyme activity. The purified
      protease, after being subjected to sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis, was found to have a molecular mass of 38.5 kDa. The enzyme was
      solvent-and surfactant-stable and showed activity even after 24 h incubation
      along with various commercially available detergents. This enzyme possessed
      dehairing properties for animal hide after 16 h of incubation at room
      temperature. From these results it is evident that cow dung is a potential
      substrate for the production of a detergent-stable, dehairing protease by B.
      subtilis. This enzyme has a lot of potential applications in the detergent and
      leather-processing industries. 

PMID- 23961376
TI  - Solving Cauchy reaction-diffusion equation by using Picard method.
AB  - In this paper, Picard method is proposed to solve the Cauchy reaction-diffusion
      equation with fuzzy initial condition under generalized H-differentiability. The
      existence and uniqueness of the solution and convergence of the proposed method
      are proved in details. Some examples are investigated to verify convergence
      results and to illustrate the efficiently of the method. Also, we obtain the
      switching points in examples. 

PMID- 23961377
TI  - Haliscosamine: a new antifungal sphingosine derivative from the Moroccan marine
      sponge Haliclona viscosa.
AB  - In the aim of searching for new antifungal products from marine origin, we have
      isolated a sphingosine derivative, (9Z)-2-amino-docos-9-ene-1,3,13,14-tetraol
      (Haliscosamine) from the Moroccan sea sponge Haliclona viscosa using bio-guided
      (antifungal) HPLC methods. The molecular structure of this compound was
      elucidated by spectrometric techniques IR, UV, MS and NMR. The isolated
      metabolite showed a significant antifungal activity against Cryptococcus and
      Candida species and a weak general toxicity in the brine shrimp lethality test.
      Further research is needed to study its in vivo activity, as well as to elucidate
      the mechanism underlying its activity in the hope of a future use in medical
      mycology. 

PMID- 23961378
TI  - A CMMI-based approach for medical software project life cycle study.
AB  - In terms of medical techniques, Taiwan has gained international recognition in
      recent years. However, the medical information system industry in Taiwan is still
      at a developing stage compared with the software industries in other nations. In
      addition, systematic development processes are indispensable elements of software
      development. They can help developers increase their productivity and efficiency
      and also avoid unnecessary risks arising during the development process. Thus,
      this paper presents an application of Light-Weight Capability Maturity Model
      Integration (LW-CMMI) to Chang Gung Medical Research Project (CMRP) in the
      Nuclear medicine field. This application was intended to integrate user
      requirements, system design and testing of software development processes into
      three layers (Domain, Concept and Instance) model. Then, expressing in structural
      System Modeling Language (SysML) diagrams and converts part of the manual effort
      necessary for project management maintenance into computational effort, for
      example: (semi-) automatic delivery of traceability management. In this
      application, it supports establishing artifacts of "requirement specification
      document", "project execution plan document", "system design document" and
      "system test document", and can deliver a prototype of lightweight project
      management tool on the Nuclear Medicine software project. The results of this
      application can be a reference for other medical institutions in developing
      medical information systems and support of project management to achieve the aim
      of patient safety. 

PMID- 23961379
TI  - Development, inheritance and breeding potential of a recessive genic male sterile
      line D248A in Sesame (Sesamum indicum L.).
AB  - Genic male sterility (GMS) has great potential for heterosis exploitation in
      sesame (Sesamum indicum L.). Two spontaneous male-sterile plants were discovered
      in a Chinese sesame cultivar (Zhuzhi 4) in 2006. By consecutive sib mating with
      fertile plants from Zhuzhi 4, a new sterile line, D248A, was developed. Anatomy
      studies showed that D248A has thin, small and greenish anthers on which there are
      no or little pollen grains. The pollens are irregularly shaped and completely
      aborted, resulting in no germination and no formation of pollen tubes as revealed
      by acetocarmine stain or semi-solid suspension culture. Furthermore, D248A has a
      better performance in growth vigor, bloom duration and yield per plant than the
      other GMS lines (i.e. 95 ms-2A and 95 ms-5A). To investigate the inheritance mode
      of fertility, D248A was crossed and backcrossed with six varieties, and a
      segregating ratio of 3:1 and 1:1 for fertile and sterile plants was observed in
      F2 and BC1 populations, respectively. These results suggested that D248A is
      controlled by a recessive GMS gene. The average yield of four D248A-derived F1
      hybrids is as high as 1695 kg.ha(-1), which is almost twice of that of 95 ms-5A
      derived F1 hybrids. These results indicated that this newly developed recessive
      GMS line has great potential in sesame hybrid breeding. 

PMID- 23961380
TI  - Is the sentinel lymph node biopsy more sensitive for the identification of
      positive lymph nodes in breast cancer than the axillary lymph node dissection?
AB  - Since the routine clinical use of the sentinel lymph node (SLN) procedure,
      questions have been raised concerning an increase in the overall percentage of
      node-positive patients. The goal of our study was to compare the sensitivity of
      the SLN procedure and the axillary lymph node dissection (ALND) for the
      identification of positive lymph nodes in breast cancer. The incidence of
      axillary node metastasis in SLNB and ALND specimens from patients undergoing
      operative treatment of a primary breast carcinoma was compared retrospectively.
      Logistic regression models were used to analyze the effect of various predictors
      on the presence of positive lymph nodes. We constructed a multivariate model
      including the procedure and these predictors that have shown to be related to
      lymph node involvement in univariate analysis. The probability of finding
      positive lymph nodes was thus calculated in both groups correcting for relevant
      predictors of lymph node involvement. The SLNB group included 830 patients, the
      ALND group 320. In a multivariate analysis, adjusting for the number of foci,
      tumor location in the breast, tumor size, LVI, ER, PR, tumor grade and
      histological subtype, the probability of finding positive lymph nodes was higher
      with SLNB procedure than with an ALND. However, this difference was not
      statistically significant (OR 0.7635; CI 0.5334-1.0930, p 0.1404). For comparable
      tumors, SLNB procedure is at least as sensitive as ALND for detecting positive
      lymph nodes. 

PMID- 23961382
TI  - What is the accordion effect?: harmonizing Bratman's principles F and D.
AB  - In an article about the accordion effect Michael Bratman pointed out some
      difficulties in Joel Feinberg's original description of it, which he calls
      "language relativity". In this comment I do not contend any of Bratman's
      conclusions, but try to resolve the tension noted by Bratman. I believe that his
      analysis of Feinberg and Davidson is detrimental to the study of the accordion
      effect since the difficulties he mentions can be explained by the context in
      which Feinberg gives his account of the accordion effect. Because of the focus of
      his essay, Feinberg is using the accordion effect not, as most scholars after him
      have done, to redescribe actions to include their consequences, but to
      disassemble action sentences to find forms of causality "hidden" in them. Such a
      reading of Feinberg explains the odd features of his description, aligns it with
      later work on the topic and enables a uniform understanding of the phenomenon. 

PMID- 23961381
TI  - Performance of breast cancer screening methods and modality among Chinese women:
      a report from a society-based breast screening program (SBSP) in Shanghai.
AB  - To evaluate the screening performance of individual and combined use of clinical
      breast examination, ultrasonography and mammography in Chinese women, we
      conducted a biennial breast cancer screening program among 14,464 women aged 35
      to 74 years old who lived in Qibao County, Minhang district of Shanghai, China,
      between May 2008 and Sept 2012. All participants were submitted to clinical
      breast examination, and then women with positive results and all women at age of
      45-69 years old were preformed breast ultrasonography and mammography. The
      examination results were compared against pathological findings as the gold
      standard of reference. A total of 66 women were diagnosed with breast cancer in
      the two rounds of the screening, yielding an incident rate of 194 per 100,000
      person-years. The sensitivity of clinical breast examination, ultrasonography and
      mammography alone were 61.4%, 53.7% and 67.3%, respectively. While mammography
      performed better in elder age groups and hormone receptor positive disease
      groups, ultrasonography had a higher sensitivity in younger age group and did not
      differ in sensitivity by estrogen receptor or progesterone receptor status.
      Combined use of the two imaging examinations increased the sensitivity in almost
      all age groups, but had a higher sensitivity in hormone receptor positive cancers
      than in those negative. Our results suggest that the Qibao modality is an
      effective strategy for breast cancer screening among Chinese women, especially
      for early detection of elder and hormone receptor positive breast cancer. 

PMID- 23961383
TI  - Effects of concentration, temperature and solvent composition on density and
      apparent molar volume of the binary mixtures of cationic-anionic surfactants in
      methanol-water mixed solvent media.
AB  - The accurate measurements on density of the binary mixtures of
      cetyltrimethylammonium bromide and sodium dodecyl sulphate in pure water and in
      methanol(1) + water (2) mixed solvent media containing (0.10, 0.20, and 0.30)
      volume fractions of methanol at 308.15, 318.15, and 323.15 K are reported. The
      concentrations are varied from (0.03 to 0.12) mol.l(-1) of sodium dodecyl
      sulphate in presence of ~ 5.0*10(-4) mol.l(-1) cetyltrimethylammonium bromide.
      The results showed almost increase in the densities with increasing surfactant
      mixture concentration, also the densities are found to decrease with increasing
      temperature over the entire concentration range, investigated in a given mixed
      solvent medium and these values are found to decrease with increasing methanol
      content in the solvent composition. The concentration dependence of the apparent
      molar volumes appear to be negligible over the entire concentration range,
      investigated in a given mixed solvent medium and the apparent molar volumes
      increase with increasing temperature and are found to decrease with increasing
      methanol content in the solvent composition. 

PMID- 23961384
TI  - A collaborative working environment for small group meetings in Second Life.
AB  - This paper presents the SLMeetingRoom, a virtual reality online environment to
      support group meetings of geographically dispersed participants. A prototype was
      developed to demonstrate the feasibility of the approach using the Second Life
      platform. Ten additional components had to be added to Second Life environment to
      support group work essential activities such as participants' communication,
      tasks' and participants' coordination, participants' collaboration and work
      evolution's perception. Empirical studies, both pilot and experiment, were
      developed comparing four different meeting settings: face-to-face,
      videoconference, stand Second Life and SLMeetingRoom. The study involved graduate
      students enrolled in the Interface and Multimedia discipline at the Fluminense
      Federal University (UFF) in Brazil. Results indicated that groups working within
      SLMeetingRoom environment presented similar results as face-to-face meeting as
      far as sense of presence is concerned and with low cognitive effort. Task
      completion and degree of participation were not affected by the meeting set up.
      It was concluded that Second Life, in conjunction with the SLMeetingRoom
      components, is a good tool for holding synchronous remote meetings and coexists
      with other electronic meeting technologies. 

PMID- 23961385
TI  - Maternal factors contributing to under-five mortality at birth order 1 to 5 in
      India: a comprehensive multivariate study.
AB  - The objective of the study is to assess maternal factors contributing to under
      five mortality at birth order 1 to 5 in India. Data for this study was derived
      from the children's record of the 2007 India National Family Health Survey, which
      is a nationally representative cross-sectional household survey. Data is
      segregated according to birth order 1 to 5 to assess mother's occupation,
      Mother's education, child's gender, Mother's age, place of residence, wealth
      index, mother's anaemia level, prenatal care, assistance at delivery , antenatal
      care, place of delivery and other maternal factors contributing to under-five
      mortality. Out of total 51555 births, analysis is restricted to 16567 children of
      first birth order, 14409 of second birth order, 8318 of third birth order, 5021
      of fourth birth order and 3034 of fifth birth order covering 92% of the total
      births taken place 0-59 months prior to survey. Mother's average age in years for
      birth orders 1 to 5 are 23.7, 25.8, 27.4, 29 and 31 years, respectively. Most
      mothers whose children died are Hindu, with no formal education, severely anaemic
      and working in the agricultural sector. In multivariate logistic models, maternal
      education, wealth index and breastfeeding are protective factors across all birth
      orders. In birth order model 1 and 2, mother's occupation is a significant risk
      factor. In birth order models 2 to 5, previous birth interval of lesser than 24
      months is a risk factor. Child's gender is a risk factor in birth order 1 and 5.
      Information regarding complications in pregnancy and prenatal care act as
      protective factors in birth order 1, place of delivery and immunization in birth
      order 2, and child size at birth in birth order 4. Prediction models demonstrate
      high discrimination that indicates that our models fit the data. The study has
      policy implications such as enhancing the Information, Education and
      Communication network for mothers, especially at higher birth orders, in order to
      reduce under-five mortality. The study emphasises the need of developing
      interventions to address the issues of anaemia, mothers working in the
      agricultural sector and improving relevant literacy among mothers. 

PMID- 23961386
TI  - Clinicopathological features and immunohistochemical detection of antigens in
      acute experimental Streptococcus agalactiae infection in red tilapia (Oreochromis
      spp.).
AB  - This study investigates the clinicopathological features of acute experimental
      streptococcosis in red tilapia using various routes of infection; intraperitoneal
      (IP), immersion (IM) and immersion cut (IC). Twenty four red tilapia in
      duplicates were inoculated intraperitoneally with 10(9) CFU/ml of S. agalactiae
      while another sets: intact, one with sharp cut at the tail end were exposed to
      bacterial inoculums 10(9) CFU/ml diluted in water while two groups of control
      fish were similarly manipulated. Clinical signs were recorded; samples from the
      gills, brain, eyes and kidneys were also taken for bacterial isolation and
      histopathology. Immunohistochemistry (IHC) and polymerase chain reaction (PCR)
      were employed to detect the antigen. The diseased fish showed skin, fin
      haemorrhages and exophthalmia with obvious signs in IP at 2 hpc followed by IC
      and IM at 4 hpc. The lesions were noticed earlier in the kidney and most severe
      in IP. IHC detected antigen as early as PCR and isolation with intense staining
      in blood vessel lumen and wall, macrophages in choroid, focal haemorrhage in the
      renal interstitium and meninges especially in IP followed by IC and IM. The
      immunolocalisation of the antigen described for the first time further explain
      the pathogenesis of streptococcosis in red tilapia. 

PMID- 23961387
TI  - Antimicrobial susceptibility pattern of clinical isolates from cases of ear
      infection using amoxicillin and cefepime.
AB  - The aim of the present study was to determine the sensitivity pattern of clinical
      isolates of otitis media. During the last few decades, the occurrence of otitis
      media seems to have been rising probably because of prevalence of multidrug
      resistant Pseudomonas aeruginosa and beta-lactamase producing Staphylococcus
      aureus in the pathogenesis of otitis media. Pseudomonas aeruginosa and
      Staphylococcus aureus were the most common causative microorganisms of ear
      infection. Keeping in view the importance of these pathogens, the present study
      had been designed to determine the sensitivity pattern of clinical isolates of
      otitis media. These isolates were collected from different hospitals and
      pathological laboratories of Karachi and their sensitivity against cefepime and
      amoxicillin were determined by using disk diffusion method. The results have
      shown that Pseudomonas aeruginosa was the most common causative microorganism of
      ear infection. Cefepime, a fourth generation cephalosporin appeared to be an
      effective antibiotic against Pseudomonas aeruginosa and Staphylococcus aureus. 

PMID- 23961388
TI  - Integrated electronic prescribing and robotic dispensing: a case study.
AB  - INTRODUCTION: To quantify the benefits of electronic prescribing directly linked
      to a robotic dispensing machine. CASE DESCRIPTION: Quantitative case study
      analysis is used on a single case. Hospital A (1,000 beds) has used an integrated
      electronic prescribing system for 10 years, and in 2009 linked two robotic
      dispensing machines to the system. The impact on dispensing error rates (quality)
      and efficiency (costs) were assessed. EVALUATION AND DISCUSSION: The
      implementation delivered staff efficiencies above expectation. For the out
      patient department, this was 16% more than the business case had suggested. For
      the in-patients dispensary, four staff were released for re-deployment.
      Additionally, L500,000 in stockholding efficiency above that suggested by the
      business case was identified. Overall dispensing error rates were not adversely
      affected and products dispensed by the electronic prescribing - robot system
      produced zero dispensing errors. The speed of dispensing increased also, as the
      electronic prescribing - robot combination permitted almost instantaneous
      dispensing from the point of a doctor entering a prescription. CONCLUSION: It was
      significant that the combination of electronic prescribing and a robot eliminated
      dispensing errors. Any errors that did occur were not as a result of the
      electronic prescribing - robotic system (i.e. the product was not stocked within
      the robot). The direct linking of electronic prescribing and robots as a
      dispensing system together produces efficiencies and improves the quality of the
      dispensing process.

PMID- 23961389
TI  - Automatic topic identification of health-related messages in online health
      community using text classification.
AB  - To facilitate patient involvement in online health community and obtain
      informative support and emotional support they need, a topic identification
      approach was proposed in this paper for identifying automatically topics of the
      health-related messages in online health community, thus assisting patients in
      reaching the most relevant messages for their queries efficiently. Feature-based
      classification framework was presented for automatic topic identification in our
      study. We first collected the messages related to some predefined topics in a
      online health community. Then we combined three different types of features, n
      gram-based features, domain-specific features and sentiment features to build
      four feature sets for health-related text representation. Finally, three
      different text classification techniques, C4.5, Naive Bayes and SVM were adopted
      to evaluate our topic classification model. By comparing different feature sets
      and different classification techniques, we found that n-gram-based features,
      domain-specific features and sentiment features were all considered to be
      effective in distinguishing different types of health-related topics. In
      addition, feature reduction technique based on information gain was also
      effective to improve the topic classification performance. In terms of
      classification techniques, SVM outperformed C4.5 and Naive Bayes significantly.
      The experimental results demonstrated that the proposed approach could identify
      the topics of online health-related messages efficiently. 

PMID- 23961390
TI  - Juvenile growth and survival of the apple snail Pomacea canaliculata
      (Caenogastropoda: Ampullariidae) reared at different constant temperatures.
AB  - BACKGROUND: Pomacea canaliculata is a freshwater snail that cultured under
      certain conditions could provide interesting rewards in research and aquaculture.
      P. canaliculata is usually reared at 25 degrees C, though the optimal temperature
      for culturing this species, that balances growth and survival rates, is so far
      unknown. In this work we present results of growth and survival of cohorts reared
      in the laboratory at different constant water temperatures (15, 20, 25, 30 and 35
      degrees C) during the pre-reproductive period. FINDINGS: Two different groups
      were recognized among the five treatments: the two lower temperatures (15 and 20
      degrees C) that showed no mortality but with very low growth rates and the
      treatments of 25, 30 and 35 degrees C in which snails grew faster but displayed a
      reduction in survival as temperature increases. After 10 weeks, the mean shell
      lengths attained at 30 and 35 degrees C were only 2-3 mm higher than that of the
      treatment of 25 degrees C and were not statistically different. CONCLUSIONS: Our
      results support using water temperatures of 25 degrees C for the rearing of
      cohorts when the objective is to quickly obtain numerous large snails.
      Temperatures of 15 and 20 degrees C may be appropriate if the aim is to preserve
      juveniles for long periods with a very low risk of mortality. The results
      reported here will be useful to the scheduling of laboratory trials intended for
      basic research, snail control or mass rearing for different applications of this
      species.

PMID- 23961391
TI  - Gravity inversion of a fault by Particle swarm optimization (PSO).
AB  - Particle swarm optimization is a heuristic global optimization method and also an
      optimization algorithm, which is based on swarm intelligence. It comes from the
      research on the bird and fish flock movement behavior. In this paper we introduce
      and use this method in gravity inverse problem. We discuss the solution for the
      inverse problem of determining the shape of a fault whose gravity anomaly is
      known. Application of the proposed algorithm to this problem has proven its
      capability to deal with difficult optimization problems. The technique proved to
      work efficiently when tested to a number of models. 

PMID- 23961392
TI  - Controlled root targeted delivery of fertilizer using an ionically crosslinked
      carboxymethyl cellulose hydrogel matrix.
AB  - AIMS: The recent increases in food prices caused by the corresponding increases
      in fertilizer costs have highlighted the demand for reducing the overuse of
      fertilizers in industrial agriculture. There has been increasing interest in
      developing plant root-targeted delivery (RTD) of fertilizers in order to address
      the problem of inefficient fertilizer use. The aim of this study is to develop a
      low cost controlled release device to deliver fertilizers to plant roots and
      thereby increase fertilizer use efficiency. METHODS: The Root Targeted Delivery
      Vehicle (RTDV) is formed by dissolving Carboxymethyl Cellulose (CMC) chains in
      water, mixing it with liquid fertilizer and crosslinking using iron and calcium
      salts. Basic measurements quantifying nutrient release and green house growth
      trials were carried out to evaluate fertilizer use efficiency on wheat growing in
      nutrient depleted soil media. RESULTS: Growing wheat in nutrient depleted media
      showed that the RTDV permits a 78% reduction in the amount of fertilizer needed
      to achieve similar levels of plant yield in these conditions. Quantifying the
      losses associated with the RTDV synthesis showed that optimizing manufacturing
      could possibly increase this value as high as 94%. Furthermore, the delivery
      device showed a similar lifetime in soil to the plant's growth cycle, delivering
      fertilizer over the course of the plant's growth before removal from soil by
      degradation. CONCLUSIONS: These results illustrate the importance of fertilizer
      delivery in facilitating absorption and may have potential to vastly increase the
      use efficiency of fertilizers in soil, resulting in a significant reduction of
      costs and environmental damage. With more in depth study to quantify the
      fertilizer release and refine the device, there is great potential for the use of
      the RTDV as an effective means to increase fertilizer use efficiency in
      agriculture.

PMID- 23961393
TI  - How Transcranial Doppler can assess the effect of hyperosmolar therapy and the
      degree of circulatory compromise in acute brain herniation.
AB  - Patients in acute neurological extremes secondary to refractory intracranial
      hypertension are challenging because of the complex management options available
      to them, especially when compounded with signs of brainstem compromise. Objective
      evidence of cerebral circulatory compromise is often lacking. We present a case
      in which an objective evaluation of a cerebral circulatory compromise was
      documented using transcranial Doppler as well as its resolution with hyperosmolar
      therapy. 

PMID- 23961394
TI  - Barriers and facilitators to self-care in chronic heart failure: a meta-synthesis
      of qualitative studies.
AB  - Chronic heart failure (CHF) is a costly condition that places large demands on
      self-care. Failure to adhere with self-care recommendations is common and
      associated with frequent hospitalization. Understanding the factors that enable
      or inhibit self-care is essential in developing effective health care
      interventions. This qualitative review was conducted to address the research
      question, "What are the barriers and facilitators to self-care among patients
      with CHF?" Electronic databases including Medline, EMBASE, CINAHL, Web of
      Science, Scopus and Google scholar were searched. Articles were included if they
      were peer reviewed (1995 to 2012), in English language and investigated at least
      one contextual or individual factor impacting on self-care in CHF patients >
      18years. The criteria defined by Kuper et al. including clarity and
      appropriateness of sampling, data collection and data analysis were used to
      appraise the quality of articles. Twenty-three articles met the inclusion
      criteria. Factors impacting on self-care were included factors related to
      symptoms of CHF and the self-care process; factors related to personal
      characteristics; and factors related to environment and self-care system.
      Important factors such as socioeconomic situation and education level have not
      been explored extensively and there were minimal data on the influence of age,
      gender, self-confidence and duration of disease. Although there is an emerging
      literature, further research is required to address the barriers and facilitators
      to self-care in patients with CHF in order to provide an appropriate guide for
      intervention strategies to improve self-care in CHF. 

PMID- 23961395
TI  - Pediatric robotic assisted laparoscopic nephropexy: case study.
AB  - We describe pediatric robotic assisted laparoscopic left nephropexy in a 12-year
      old female for symptomatic nephroptosis after partial nephroureterectomy. 

PMID- 23961396
TI  - Non-conventional induction strategies for production of subunit swine erysipelas
      vaccine antigen in rE. coli fed-batch cultures.
AB  - In spite of the large number of reports on fed-batch cultivation of E. coli,
      alternative cultivation/induction strategies remain to be more deeply exploited.
      Among these strategies, it could be mentioned the use of complex media with
      combination of different carbon sources, novel induction procedures and feed flow
      rate control matching the actual cell growth rate. Here, four different carbon
      source combinations (glucose, glycerol, glucose + glycerol and auto-induction) in
      batch media formulation were compared. A balanced combination of glucose and
      glycerol in a complex medium formulation led to: fast growth in the batch-phase;
      reduced plasmid instability by preventing early expression leakage; and protein
      volumetric productivity of 0.40 g.L(-1).h(-1). Alternative induction strategies
      were also investigated. A mixture of lactose and glycerol as supplementary medium
      fully induced a high biomass population, reaching a good balance between specific
      protein production (0.148 gprot.gDCW (-1)) and volumetric productivity (0.32 g.L(
      1).h(-1)). The auto-induction protocol showed excellent results on specific
      protein production (0.158 gprot.gDCW (-1)) in simple batch cultivations. An
      automated feed control based on the on-line estimated growth rate was
      implemented, which allowed cells to grow at higher rates than those generally
      used to avoid metabolic overflow, without leading to acetate accumulation. Some
      of the protocols described here may provide a useful alternative to standard
      cultivation and recombinant protein production processes, depending on the
      performance index that is expected to be optimized. The protocols using glycerol
      as carbon source and induction by lactose feeding, or glycerol plus glucose in
      batch medium and induction by lactose pulse led to rSpaA production in the range
      of 6 g.L(-1), in short fed-batch processes (16 to 20 h) with low accumulation of
      undesired side metabolites. 

PMID- 23961397
TI  - Fabrication of hollow PbS nanospheres and application in phenol release.
AB  - This article demonstrates a versatile method to prepare the hollow PbS
      nanospheres via the template method. First, the latex poly (vinyl benzyl
      chloride) (PVBC) nanoparticles were synthesized by the radical polymerization,
      followed by the atom transfer reversible polymerization of lead (II)
      dimethacrylate (Pb (MA)2) on the surfaces of the latex nanoparticles. Then, the
      ethanethioamide was reacted with the nanoparticles to afford the PbS. By
      calcination at 600 degrees C for 6 h, the template was removed to obtain the
      hollow PbS nanospheres. The structure, morphology and optical properties of the
      hollow PbS nanospheres were carefully investigated. The received hollow PbS
      nanospheres could be used for the controlled release of phenol after absorbing
      phenol solution. 

PMID- 23961398
TI  - Computational modeling of the p7 monomer from HCV and its interaction with small
      molecule drugs.
AB  - Hepatitis C virus p7 protein is a 63 amino acid polytopic protein with two
      transmembrane domains (TMDs) and one of the prime targets for anti HCV drug
      development. A bio-inspired modeling pathway is used to generate plausible
      computational models of the two TMDs forming the monomeric protein model. A
      flexible region between Leu-13 and Gly-15 is identified for TMD11-32 and a region
      around Gly-46 to Trp-48 for TMD236-58. Mutations of the tyrosine residues in
      TMD236-58 into phenylalanine and serine are simulated to identify their role in
      shaping TMD2. Lowest energy structures of the two TMDs connected with the loop
      residues are used for a posing study in which small molecule drugs BIT225,
      amantadine, rimantadine and NN-DNJ, are identified to bind to the loop region.
      BIT225 is identified to interact with the backbone of the functionally important
      residues Arg-35 and Trp-36. 

PMID- 23961400
TI  - Assessment of the further improved (G'/G)-expansion method and the extended tanh
      method in probing exact solutions of nonlinear PDEs.
AB  - The (G'/G)-expansion method is one of the most direct and effective method for
      obtaining exact solutions of nonlinear partial differential equations (PDEs). In
      the present article, we construct the exact traveling wave solutions of nonlinear
      evolution equations in mathematical physics via the (2 + 1)-dimensional breaking
      soliton equation by using two methods: namely, a further improved (G'/G)
      expansion method, where G(xi) satisfies the auxiliary ordinary differential
      equation (ODE) [G'(xi)](2) = p G (2)(xi) + q G (4)(xi) + r G (6)(xi); p, q and r
      are constants and the well known extended tanh-function method. We demonstrate,
      nevertheless some of the exact solutions bring out by these two methods are
      analogous, but they are not one and the same. It is worth mentioning that the
      first method has not been exercised anybody previously which gives further exact
      solutions than the second one. PACS numbers 02.30.Jr, 05.45.Yv, 02.30.Ik. 

PMID- 23961399
TI  - Reasons of not having breast reconstruction: a historical cohort of 1937 breast
      cancer patients undergoing mastectomy.
AB  - BACKGROUND: The aims of the study were to investigate the factors associated with
      not having breast reconstruction following mastectomy and to assess patient
      satisfaction with information on reconstruction. PATIENTS AND METHODS: We
      analysed a historical cohort of 1937 consecutive patients who underwent
      mastectomy at Institut Curie between January 2004 and February 2007. Their
      sociodemographic and clinicobiological characteristics were recorded in a
      prospective database. A questionnaire was sent to 10% of nonreconstructed
      patients. RESULTS: The proportion of patients with invasive cancer was 82.7%. The
      rate of nonreconstruction in patients with in situ and invasive cancer was 34.6%
      and 74.9%, respectively. On multivariate analysis, only employment outside the
      home was associated with reconstruction in patients with in situ cancer (p <
      0.001). In patients with invasive cancer, employment status (p < 0.001) and
      smoking (p = 0.045) were associated with reconstruction, while age > 50, ASA
      score >1, radiotherapy (p < 0.0001) and metastatic status (p = 0.018) were
      associated with nonreconstruction. For 80% of questionnaire responders,
      nonreconstruction was a personal choice, mainly for the following reasons:
      refusal of further surgery, acceptance of body asymmetry, risk of complications
      and advanced age. Information on reconstruction was entirely unsatisfactory or
      inadequate for 62% of patients. CONCLUSION: Better understanding the factors that
      influence decision of nonreconstruction can help us adapt the information to
      serve the patient's personal needs.

PMID- 23961401
TI  - Effect of tetracycline administration on serum amylase activity in calves.
AB  - Tetracycline and related compounds are used extensively as broad spectrum
      antibiotics in the treatment of bacterial infections in ruminants. Tetracycline
      may cause acute pancreatitis which may result in increased serum amylase
      activity. However, it has been shown that administration of oxytetracycline in
      human results in decrease serum amylase activity. In this study changes in serum
      amylase activity were measured in 20 clinically healthy calves following
      intravenous injection of oxytetracycline hydrochloride at 10 mg/kg of body
      weight. Blood samples were collected at 30, 60, and 120 minutes after
      oxytetracycline injection. Serum amylase activity was measured using the
      amyloclastic assay. The activity of serum amylase was increased significantly (P
      < 0.05) at 30 (40.5%), 60 (35.1%), and 120 (39.3%) minutes after oxytetracycline
      hydrochloride administration. To the authors' knowledge this is the first study
      on the acute effect of tetracycline administration on serum amylase activity in
      calves. 

PMID- 23961402
TI  - Hip structural analysis: a comparison of DXA with CT in postmenopausal Japanese
      women.
AB  - Geometry of the proximal femur is one determinant of fracture risk, and can be
      analyzed by a simple method using dual-energy X-ray absorptiometry (DXA). The aim
      of the present study was to investigate the accuracy of hip structural analysis
      (HSA) using clinical data in postmenopausal Japanese women. A total of 184
      postmenopausal women aged 51-88 years (mean, 70.5 +/- 8.7 years) who underwent
      artificial joint replacement surgery for osteoarthrosis of the hip or knee joint
      were included. Computed tomography (CT) data from preoperative assessment were
      utilized for analysis of proximal femoral geometry (CT-HSA) using QCTPro Software
      (Mindways Software Inc., Austin, TX) and compared with HSA results based on DXA
      (DXA-HSA). The results of femoral geometry were further compared with a CT-based
      finite-element method (CT/FEM). There was moderate to high correlation between
      DXA-HSA and CT-HSA (r=0.60-0.90, p<0.001), except for the buckling ratio in the
      intertrochanteric region. Moreover, the correlation of HSA with CT/FEM was
      similar between DXA-HSA and CT-HSA. The present results suggest that the geometry
      of proximal femoral cross sections can be reasonably well characterized using
      DXA. 

PMID- 23961403
TI  - Translation, cross-cultural adaptation and validation of the Portuguese version
      of the DYMUS questionnaire for the assessment of dysphagia in multiple sclerosis.
AB  - Translation, cross-cultural adaptation and validation of the DYMUS questionnaire
      for the assessment of dysphagia in multiple sclerosis. The original English
      version of the DYMUS was translated using the forward-backward technique, cross
      culturally adaptated, pilot-tested in 40 patients, and then applied to 100
      multiple sclerosis patients to assess the reliability and construct validity.
      Construct validity was assessed by Mann-Whitney test and Spearman's correlation
      coefficient (rs). The internal consistency of the questionnaire was evaluated
      using Cronbach's alpha coefficient and inter-item correlation. DYMUS-BR internal
      consistency was high (Cronbach's alpha= 0.72); Cronbach's alpha was 0.65 for the
      'dysphagia for solids' subscale and 0.67 for the 'dysphagia for liquids' subscale
      and positive inter-item correlations was found between all items, except for
      weight loss question. Significant association (p<0.001) and correlation (rs =
      0,357; p = 0.01) was found between DYMUS-BR and dysphagia self-assessment. The
      DYMUS-BR questionnaire maintained the characteristics of that originally
      described, demonstrating to be a reliable, valid, easy and consistent tool to be
      used by health professionals for preliminary selection of Brazilian MS patients
      who need more specific instrumental analyses of swallowing. 

PMID- 23961404
TI  - Culture transition, acculturation and intimate partner homicide.
AB  - This article suggests an up-to-date, integrative theoretical/empirical model to
      explain IPH against Ethiopian women, as an example of IPH against women from
      patriarchal cultures in general, emphasizing the fact that psychological
      explanations, as well as socio-cultural ones alone, are insufficient for an
      understanding of this phenomenon. A full analysis requires the combination of the
      different points of view of all the parties involved. Only an integrative model,
      incorporating these different mindsets, can clarify the complex phenomenon of IPH
      among Ethiopian immigrants. Following a comprehensive review of the original
      characteristics of Ethiopian culture and its transformation after immigration to
      Israel, this article introduces the risk factors and triggers for IPH against
      Ethiopian women. 

PMID- 23961405
TI  - Modeling and prediction of cytotoxicity of artemisinin for treatment of the
      breast cancer by using artificial neural networks.
AB  - While artemisinin is known as anticancer medication with favorable remedial
      effects, its side effects must not be neglected. In order to reduce such side
      effects and increase artemisinin therapeutic index, nano technology has been
      considered as a new approach. Liposome preparation is supposed to be one of the
      new methods of drug delivery. To prepare the desired nanoliposome, certain
      proportions of phosphatidylcholine, cholesterol and artemisinin are mixed
      together. Besides, in order to achieve more stability, the formulation was
      pegylated by polyethylene glycol 2000 (PEG 2000). Mean diameter of nanoliposomes
      was determined by means of Zeta sizer. Encapsulation was calculated 96.02% in
      nanoliposomal and 91.62% in pegylated formulation. Compared to pegylated
      formulation, the percent of released drug in nanoliposomal formulation was more.
      In addition, this study reveals that cytotoxicity effect of pegylated
      nanoliposomal artemisinin was more than nanoliposomal artemisinin. Since
      artificial neural network shows high possibility of nonlinear modulation, it is
      used to predict cytotoxicity effect in this study, which can precisely indicate
      the cytotoxicity and IC50 of anticancer drugs. 

PMID- 23961406
TI  - Probing horseradish peroxidase catalyzed degradation of azo dye from tannery
      wastewater.
AB  - Biocatalysis based effluent treatment has outclassed the presently favored
      physico-chemical treatments due to nil sludge production and monetary savings.
      Azo dyes are commonly employed in the leather industry and pose a great threat to
      the environment. Here, we show the degradation of C. I. Acid blue 113 using
      horseradish peroxidase (HRP) assisted with H2O2 as a co-substrate. It was
      observed that 0.08 U HRP can degrade 3 mL of 30 mg/L dye up to 80% within 45 min
      with the assistance of 14 MUL of H2O2 at pH 6.6 and 30 degrees C. The feasibility
      of using the immobilized HRP for dye degradation was also examined and the
      results show up to 76% dye degradation under similar conditions to that of free
      HRP with the exception of longer contact time of 240 min. Recycling studies
      reveal that the immobilized HRP can be recycled up to 3 times for dye
      degradation. Kinetics drawn for the free HRP catalyzed reaction marked a lower K
      m and higher V max values, which denotes a proper and faster affinity of the
      enzyme towards the dye, when compared to the immobilized HRP. The applicability
      of HRP for treating the actual tannery dye-house wastewater was also
      demonstrated. 

PMID- 23961407
TI  - Influence of cheek support on respiratory impedance measured by forced
      oscillation technique.
AB  - The forced oscillation technique (FOT) is a useful tool to assess respiratory
      resistance and reactance during tidal breathing in patients with respiratory
      diseases, specifically asthma and chronic obstructive pulmonary disease. Although
      the FOT has been clinically used, results of respiratory impedance can be
      affected by various factors such as upper airway artifact. We investigated the
      effects of cheek support on respiratory resistance and reactance measured by a
      commercially available FOT equipment MostGraph-01. Respiratory resistance at 20
      Hz (R20) with support of the cheeks was significantly higher than those without
      the cheek support in healthy subjects. Two different cheek support protocols,
      support of the cheeks by subjects themselves and an operator, were compared in
      healthy volunteers and patients with respiratory diseases. The cheek support
      protocols significantly affected respiratory resistance at 5 Hz (R5) and
      reactance at 5 Hz (X5) in the patient group but not in the healthy subjects.
      Moreover, for X5, there was a significant interaction between cheek support
      protocols (by a subject or operator) and groups (healthy or diseased). In
      conclusion, during impedance measurements using the FOT, application of cheek
      support either by subjects or the operator is recommended to reduce upper airway
      artifacts, however, results obtained by two protocols may be different in
      patients with respiratory diseases. Contribution of the chest wall and position
      of the arms to the mechanical properties should be carefully considered in
      physiological studies in which the FOT is attempted. 

PMID- 23961408
TI  - Effect of gene polymorphisms on the mechanical properties of human tendon
      structures.
AB  - Recent studies showed that polymorphisms in alpha 1 chains of types I (COL1A1)
      and V (COL5A1) collagen, growth and differentiation factor 5 (GDF5), and matrix
      metalloproteinase 3 (MMP3) genes were associated with injuries in tendons and
      ligaments (e.g., September et al. (Br J Sports Med 43: 357-365 2009)). In the
      present study, we aimed to investigate the effects of injury-associated
      polymorphisms within these four genes on the mechanical properties of human
      tendon structures in vivo. One hundred Japanese males participated in this
      experiment. The mechanical properties of tendon structures in knee extensors and
      plantar flexors were measured using ultrasonography. All subjects were genotyped
      for COL1A1 rs1800012, COL5A1 rs12722, GDF5 rs143383, and MMP3 rs679620 single
      nucleotide polymorphisms. For COL1A1, all subjects had a GG genotype. For COL5A1,
      maximal tendon elongation and strain of individuals with a CC genotype were
      significantly greater than individuals with other genotypes (combined TT and CT)
      for knee extensors, but not for plantar flexors. For GDF5 and MMP3, there were no
      differences in the mechanical properties of tendon structures in knee extensors
      and plantar flexors among the three genotypes. The present study demonstrated
      that subjects with a CC genotype of the COL5A1 gene had more extensible tendon
      structures than those of subjects with other genotypes (combined TT and CT) for
      knee extensors, but not for plantar flexors. The results presented in this study
      need to be confirmed in a larger cohort of subjects. 

PMID- 23961409
TI  - Imipenem/cilastatin sodium (IPM/CS) as an embolic agent for transcatheter
      arterial embolisation: a preliminary clinical study of gastrointestinal bleeding
      from neoplasms.
AB  - PURPOSE: To evaluate the feasibility and usefulness of imipenem/cilastatin sodium
      (IPM/CS) as an embolic agent for intestinal bleeding from neoplasms. MATERIALS
      AND METHODS: Seven patients who underwent 11 transarterial embolisations (TAEs)
      using IPM/CS as an embolic material for duodenal or small/large intestinal tumour
      bleeding from January 2004 to December 2011 were retrospectively evaluated. A
      mixture of IPM/CS and contrast medium was introduced through the microcatheter
      positioned at the feeding artery to the tumour until extravasation disappeared or
      stasis of blood flow to the tumour staining was observed. RESULTS: Haemostasis
      was obtained in all patients. Therefore, the technical success rate was 100%.
      Rebleeding was observed in four patients. All of them underwent repeat TAE using
      IPM/CS, and haemostasis was obtained successfully. No complication was identified
      following laboratory and clinical examinations. No haemorrhagic death occurred.
      Haemorrhagic parameters, including blood haemoglobin and the amount of blood
      transfusion, improved after TAE. CONCLUSION: The safety, feasibility, and
      effectiveness of TAE using IPM/CS as an embolic material for intestinal bleeding
      from neoplasms were suggested by this study. The mild embolic effect of IPM/CS
      may be adequate for oozing from tumours. Although rebleeding may occur after
      embolotherapy using IPM/CS, repeat embolisation is effective as treatment for
      rebleeding.

PMID- 23961410
TI  - A comparative survey of genetic diversity among a set of Caricaceae accessions
      using microsatellite markers.
AB  - A preliminary survey of genetic diversity among 34 commercially popular Carica
      papaya cultivars from India and abroad, 6 accessions of Vasconcellea species and
      1 accession of Jacaratia spinosa, was done using 20 simple sequence repeat (SSR)
      markers. The SSR profiles were used to find out total number of alleles, null and
      rare alleles, Polymorphism Information Content (PIC) values and to calculate
      similarity matrix using Jaccard's coefficient. The subsequent dendrogram was made
      by unweighted pair-group method of arithmetic average (UPGMA) and neighbor
      joining method. Based on these parameters a comparison was made between the
      Indian papaya cultivars and the rest of the accessions. All the markers showed
      polymorphism and a total of 140 alleles were identified. The average number of
      alleles was 7 alleles/locus. Categorically the Vasconcellea and Jacaratia species
      had 54 alleles, the 7 non-Indian Carica papaya accessions had 70 and the 27
      Indian accessions had 102 alleles. The average PIC value was 0.735 per marker. A
      total of 37 rare alleles were identified. Jacaratia spinosa had 17 rare alleles.
      Nineteen null alleles were detected among the Carica papaya accessions. A Carica
      papaya accession from South Africa, Hortus Gold had 5 null alleles. The genetic
      similarity among the accessions ranged from 7% to 67%. In the dendrogram, the
      Vasconcellea and Jacaratia spinosa accessions separated as a distinct cluster
      from the rest of the Carica papaya accessions. The study indicated that the
      accessions of Indian Carica papaya cultivars included in this survey are
      genetically more diverse than the non-Indian Carica papaya cultivars. 

PMID- 23961411
TI  - Enzymatic and toxigenic ability of opportunistic fungi contaminating intensive
      care units and operation rooms at Assiut University Hospitals, Egypt.
AB  - Total of 110 isolates belonging to 8 fungal species collected from intensive care
      units (ICUs) and operation rooms (ORs) at Assiut University hospitals were
      examined for their ability to produce some extracellular enzymes and mycotoxins
      which are considered as important factors involved in for fungal pathogenicity.
      The results revealed that 73, 92 and 78 out of the 110 tested isolates produced
      protease, lipase and urease respectively; meanwhile, 77 of the tested isolates
      exhibited some hemolytic activities. Chromatographic analysis (TLC) of the crude
      extract of the fungal isolates tested revealed that 79 isolates of them had the
      ability to produce at least one of these mycotoxic compounds (aflatoxins B1, B2,
      G1, gliotoxin, fumigillin, T-2, zearalenone, roridin A & E, verrucarin A & J,
      trichoveroids, satratoxin H & E). These results demonstrate that the
      opportunistic fungal species isolated from (ICUs) and (ORs) and tested exhibited
      some enzymatic and mycotoxic ability which are the most effective virulence
      factors contributing to fungal pathogenicity indicating that the management of
      infection control unit at Assiut University hospitals must be aware of not only
      bacterial but also fungal contamination. 

PMID- 23961412
TI  - Hybrid procedure using perineal and abdominal approaches for radical
      prostatocystectomy: initial experience with 16 select cases.
AB  - OBJECTIVES: To validate the feasibility and implications of a hybrid procedure
      using perineal and abdominal approaches for a radical prostatocystectomy.
      METHODS: Between March 2007 and May 2012, we performed 16 prostatocystectomy and
      simultaneous urethrectomy under a hybrid procedure using perineal and abdominal
      approach for advanced bladder cancer. The hybrid procedure was selected in each
      case, because of prostatic urethra involvement in 13 and prior treatment in 3
      (irradiation, radical retropubic prostatectomy, and sigmoidectomy, respectively).
      Two surgical teams, one responsible for the perineal approach and the other for
      the abdominal portion, performed the operation. RESULTS: The median operation
      time for the prostatocystectomy procedure was 207 minutes and median
      intraoperative blood loss was 1665 ml. The en bloc removal of the specimen was
      perfectly performed and no intraoperative difficulties and intraoperative
      complications such as rectal injury were recognized in all cases. As for
      postoperative complications associated with the exaggerated lithotomy position,
      neurologic complications and rhabdomyolysis which could be treated conservately
      were found in 1 case. Although 5 patients died from distant metastasis, local
      recurrence was not seen in any of the 16 patients during the follow-up period.
      CONCLUSION: The hybrid procedure using perineal and abdominal approach for
      radical prostatocystectomy is a well-organized procedure that can provide good
      visualization of the surgical structure around the prostate, leading to a
      reduction in or prevention of local recurrence and surgical complications even in
      the selected patient.

PMID- 23961413
TI  - Impact of environmental factors on the population dynamics, density and foraging
      activities of Odontotermes lokanandi and Microtermes obesi in Islamabad.
AB  - Affect of different environmental factors i.e., temperature, relative humidity
      and precipitation on population dynamics, density and foraging activities of
      Microtermes obesi Holmgren and Odontotermes lokanandi Chatarjee and Thakur
      (Isoptera: Termitidae) were studied from March 2010 to July 2012 in Islamabad. A
      total of 1200 poplar wooden stakes was used for monitoring the termite activities
      in Islamabad. The results showed that 65 out of 1200 poplar wooden stakes were
      found infested by both species i.e. M. obesi and O. lokanandi. Both species were
      interacting with each other in the experimental field and O. lokanandi was found
      significantly dominant. Mean yield per trap ranged from 0.83 +/- 0.20 gm to 1.12
      +/- 0.28 gm and 0.35 +/- 0.09 gm to 0.82 +/- 0.19 gm for M. obesi and O.
      lokanandi in the field, respectively. M. obesi and O. lokanandi in 1.0 gm sample
      ranged from 539.83 +/- 2.21 to 567.83 +/- 9.41 and 407.67 +/- 4.75 to 424.5 +/-
      1.15 individuals, respectively. Population of workers ranged from 93.53 +/- 1.73
      to 97.68 +/- 0.40 and 91.69 +/- 1.42 to 98.41 +/- 0.50 percent for M. obesi and
      O. lokanandi, respectively. Positive and significant correlation was found among
      atmospheric temperature, precipitation and both subterranean termite species
      i.e., M. obesi and O. lokanandi; however, the correlation was found non
      significant and negative between relative humidity and foraging activities of
      both termite species. Moreover, correlation was found positive and significant
      between atmospheric temperature and percent workers of M. obesi; while negative
      and non-significant between atmospheric temperature and percent workers of O.
      lokanandi. Negative and significant correlation was noted between relative
      humidity and percent workers of M. obesi; whereas, positive and significant
      correlation was recorded between relative humidity and percent workers of O.
      lokanandi. Positive and non-significant correlation was recorded between
      precipitation and percent workers of M. obesi; while positive and significant
      correlation was observed between precipitation and percent workers of O.
      lokanand. 

PMID- 23961414
TI  - Accuracy of axillary ultrasound in preoperative nodal staging of breast cancer -
      size of metastases as limiting factor.
AB  - Since the performance of surgical procedures of the axilla in the treatment of
      early breast cancer is decreasing, the role of axillary ultrasound (AUS) as
      staging procedere has newly to be addressed. The aim of this study was to
      determine which patient or histopathological characteristics are related to false
      negative AUS. In a retrospective study design data of 470 women with primary
      breast cancer were collected from patient charts and imaging and pathology
      records were reviewed. True positive and false negative axillary ultrasound
      groups were compared in terms of tumor size, histological subtype, grade,
      estrogen receptor (ER) and HER2 status, proliferation index, number and size of
      nodal metastases, extracapsular extension (ECE) and lymphovascular invasion
      (LVI). Of 470 patients, 166 (35%) were node positive, 79 of them with suspicious
      AUS. Factors associated with false negative AUS by univariate analysis were
      included in a multivariate model. By multivariate analysis, only size of nodal
      metastases was an independent factor for false negative AUS. In the sentinel
      lymph node biopsy (SLNB) subgroup, 45% of patients had nodal metastasis size less
      than or equal to 5 mm. In conclusion, AUS in preoperative staging of early stage
      breast cancer is limited by small size of metastases in a substantial number of
      patients. Prospective studies have to show whether small metastatic deposits
      leaving in patients in case of no axillary surgery have no negative effect on
      disease free and overall survival. 

PMID- 23961415
TI  - Computed tomographic lymphography for sentinel lymph node biopsy in male breast
      cancer: report of two cases.
AB  - Male breast cancer is rare, accounting for less than 1% of breast cancers.
      Because of its rarity evidence of the usefulness sentinel lymph node biopsy
      (SLNB) for male breast cancer has not been established. Moreover, a navigation
      system which can easily determine the incision site of SLNB is needed because a
      second incision for SLNB is necessary in most cases. We report successful
      computed tomographic lymphography (CTLG)-guided SLNB in two male breast cancer
      cases: the first patient was a 79-year-old man and the second was a 64-year-old
      man. Both had presented with a lump behind the nipple. Clinical diagnoses were
      early breast carcinoma in both cases. The second patient took tamoxifen 20 mg
      daily as neoadjuvant endocrine therapy. SLNs were clearly visualized by CTLG,
      allowing mastectomies with SLNB to be performed. Both SLNB were negative, such
      that axillary lymph node dissection was not needed. Preoperative CTLG is useful
      for visualizing lymph flow and detecting SLN in male breast cancer. 

PMID- 23961416
TI  - Energy intake, nutritional status and weight reduction in patients one year after
      laparoscopic sleeve gastrectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is increasingly popular due to
      its efficiency in reducing excess weight, however little is known about the
      nutritional status in patients after surgery. PURPOSE: To investigate how LSG
      affects energy intake, nutritional status and body weight one year after surgery.
      METHODS: A total of 150 patients (116 women) were enrolled in the study. Data on
      body weight, waist circumference and blood samples were registered preoperatively
      and after surgery. Food intake was reported 3 and 12 months postoperatively.
      RESULTS: The preoperative median BMI was 44.3 (inter quartile range 41.4-47.1),
      and was significantly reduced to 35.4 (32.6-38.6) after 3 months and further
      reduced to 30.5 (27.4-33.8) 12 months after surgery (p < 0.05). The median post
      surgery daily energy intake was significantly increased from 2971 (1982-3687) kJ
      after three months to 3840 (3046-4625) kJ twelve months postoperatively. One year
      after surgery, serum levels of folate, cobalamin, PTH and HDL cholesterol were
      significantly increased, whereas calcium, albumin, haemoglobin, creatinine, uric
      acid, CRP, glucose, insulin, insulin c-peptide, HOMA-IR, HbA1c and
      triacylglycerol were significantly decreased. Serum levels of vitamins E and D
      were unchanged after one year. The prevalence of patients with medically
      regulated type 2 diabetes was significantly reduced one year post surgery however
      no changes were seen in the prevalence of patients taking lipid lowering drugs or
      thyroxin. CONCLUSION: Based on the data obtained 12 months after surgery, LSG
      appears to be an effective treatment of morbid obesity without worsening the
      nutritional status despite the very low energy intake.

PMID- 23961417
TI  - An in silico evaluation of the ADMET profile of the StreptomeDB database.
AB  - BACKGROUND: Computer-aided drug design (CADD) often involves virtual screening
      (VS) of large compound datasets and the availability of such is vital for drug
      discovery protocols. This paper presents an assessment of the "drug-likeness" and
      pharmacokinetic profile of > 2,400 compounds of natural origin, currently
      available in the recently published StreptomeDB database. METHODS: The evaluation
      of "drug-likeness" was performed on the basis of Lipinski's "Rule of Five", while
      46 computed physicochemical properties or molecular descriptors were used to
      predict the absorption, distribution, metabolism, elimination and toxicity
      (ADMET) of the compounds. RESULTS: This survey demonstrated that, of the computed
      molecular descriptors, about 28% of the compounds within the StreptomeDB database
      were compliant, having properties which fell within the range of ADMET properties
      of 95% of currently known drugs, while about 44% of the compounds had <= 2
      violations. Moreover, about 50% of the compounds within the corresponding "drug
      like" subset showed compliance, while >83% of the "drug-like" compounds had <= 2
      violations. CONCLUSIONS: In addition to the previously verified range of measured
      biological activities, the compounds in the StreptomeDB database show interesting
      DMPK profiles and hence could represent an important starting point for hit/lead
      discovery from natural sources. The generated data are available and could be
      highly useful for natural product lead generation programs.

PMID- 23961418
TI  - Association of the HLA locus and TNF with type I autoimmune hepatitis
      susceptibility in New Zealand Caucasians.
AB  - PURPOSE: The precise etiology of autoimmune hepatitis (AIH) remains unknown,
      although a number of genetic loci have been implicated in the susceptibility of
      type 1 AIH. The purpose of this study was to test for association of these loci
      with type 1 AIH in New Zealand Caucasians. METHODS: 77 AIH patients and 485
      healthy controls were genotyped for the SNPs rs2187668 (HLA-DRB*03:01), rs660895
      (HLA-DRB*04:01), rs3749971 (HLA-A1-B8-DR3), rs231775 (CLTLA4), rs1800629 (TNF),
      and rs1800682 (FAS) using predesigned TaqMan SNP genotyping assays. Chi square
      analysis was used to test for association of allele and genotype with overall
      AIH, and with severe fibrosis and ALT levels at 6 months. RESULTS: Significant
      risk of AIH was conferred by the minor alleles of rs2187668 (OR = 2.45, 95% CI
      1.65-3.61, p < 0.0001), rs3749971 (OR = 1.89, 95% CI 1.21-2.94, p = 0.004) and
      rs1800629 (OR = 2.06, 95% CI 1.41-3.01, p = 0.0001). Multivariate analysis showed
      that rs2187668 was independently associated with type 1 AIH susceptibility (OR =
      2.40, 95% CI 1.46-3.93, p = 0.001). The C allele of FAS SNP rs1800682 was
      associated with increased risk of severe fibrosis at diagnosis (OR = 2.03, 95% CI
      1.05-3.93, p = 0.035) and with incomplete normalization of ALT levels at 6 months
      post-diagnosis (OR = 3.94, 95% CI 1.62-9.54, p = 0.0015). CONCLUSIONS: This is
      the first population-based study to investigate genetic risk loci for type 1 AIH
      in New Zealand Caucasians. We report significant independent association of HLA
      DRB1*03:01 with overall susceptibility to type 1 AIH, as well as FAS with a more
      aggressive disease phenotype.

PMID- 23961419
TI  - Factors associated with compliance to adjuvant hormone therapy in Black and White
      women with breast cancer.
AB  - BACKGROUND: Studies have demonstrated lower rates of breast cancer survival for
      Black versus White women. Factors implicated include later stages at diagnosis,
      differences in tumor biology, and lower compliance rates to adjuvant hormone
      therapy (AHT) among Black women with hormone sensitive breast cancer. We examined
      factors associated with compliance to AHT among Black and White women with
      invasive breast cancer. METHODS: Women with estrogen receptor positive (ER+), non
      metastatic breast cancer were identified by the cancer registry at the University
      of Chicago Hospital and asked to complete a mail-in survey. Compliance was
      defined by self-reported adherence to AHT >=80% at the time of the survey plus
      medical record verification of persistence (completion of 5 years of AHT).
      Logistic regression was used to determine factors associated with compliance to
      AHT. RESULTS: 197 (135 White and 62 Black) women were included in the analysis.
      97.4% of patients reported adherence to therapy. 87.4% were found to be
      persistent to therapy. Overall compliance was 87.7% with no statistically
      significant racial difference seen (87.9% in White and 87.0% in Black, P = 0.87).
      For both Black and White women, compliance was strongly associated with both
      perceived importance of AHT (OR =2.1, 95% CI:1.21-3.68,P = 0.009) and the value
      placed on their doctor's opinion about the importance of AHT (OR = 4.80, 95% CI:
      2.03-11.4, P < 0.001). CONCLUSIONS: In our cohort of Black and White women,
      perceived importance of AHT and the degree to which they valued their doctor's
      opinion correlated with overall compliance. This suggests that Black and White
      women consider similar factors in their decision to take AHT.

PMID- 23961420
TI  - Perihematomal glutamate level is associated with the blood-brain barrier
      disruption in a rabbit model of intracerebral hemorrhage.
AB  - OBJECTIVE: To observe the relationship between the perihematomal glutamate levels
      and the blood-brain barrier (BBB) permeability in a rabbit model of intracerebral
      hemorrhage (ICH). METHODS: Seventy-two rabbits were randomly divided into an
      intracerebral hemorrhage (ICH) model group and a normal control (NC) group, and
      each group of 36 rabbits was subsequently divided into 6, 12, 18, 24, 48 and 72 h
      groups (n = 6 each). An ICH model was induced by stereotactic injection of
      autologous, arterial, non-anticoagulated blood into rabbit basal ganglia. The
      same procedures were performed in the NC group, but blood was not injected. The
      rabbits were sacrificed at specific time points after the experiment began
      depending on their group. Perihematomal brain tissues were collected to determine
      glutamate levels, BBB permeability and brain water content (BWC). RESULTS: All of
      the assessed parameters were increased 6 hour after blood infusion and continued
      to gradually increase, peaking at 48 hours. Differences were observed when ICH
      values were compared with those of the NC group (p < 0.05). CONCLUSIONS:
      Perihematomal glutamate increased significantly after ICH. High levels of
      glutamate are closely associated with BBB disruption and the brain edema.
      Therefore, glutamate may play an important role in the pathogenesis of secondary
      brain injury after (ICH).

PMID- 23961421
TI  - Genetic diversity and relationship of cattle populations of East India:
      distinguishing lesser known cattle populations and established breeds based on
      STR markers.
AB  - India has 34 recognized breeds of cattle in addition to many more not
      characterized and accredited so far. It is imperative to characterize all the
      cattle germplasm of the country so as to have better breeding and conservation
      options. Thus, present study was planned for assessing genetic diversity and
      relationship between three local cattle populations (Gangatiri, Shahabadi and
      Purnea) and two established cattle breeds (Bachaur and Siri) of eastern India by
      using 21 FAO and ISAG recommended microsatellite markers. A total of 243
      unrelated DNA samples of five cattle populations were collected from respective
      habitats. A total of 304 microsatellite alleles were identified with number of
      alleles at one locus ranging from 5 to 29. The average observed heterozygosity
      lie within the narrow range of 0.681 +/- 0.04 in Purnea to 0.721 +/- 0.03 in
      Siri. Mean estimates of observed and expected heterozygosity over all loci and
      breeds were 0.704 +/- 0.02 and 0.720 +/- 0.01, respectively. In the overall
      population, the homozygote excess (FIT) of 0.073 +/- 0.02, was partly due to the
      homozygote excess within breeds (FIS = 0.026 +/- 0.02) and to a larger extent due
      to genetic differentiation among breeds (FST = 0.048 +/- 0.01). The genetic
      distance, STRUCTURE and Principal Component Analyses concluded that the Siri
      cattle are most distinct among the investigated cattle populations. Furthermore
      the analysis of genetic structure indicated that the most probable number of
      clusters is four. All analysis showed that a significant amount of genetic
      variation is maintained in local cattle populations of which Shahabadi and Purnea
      are distinct from the recognized breeds of the area and needs recognition as
      breeds. 

PMID- 23961422
TI  - Proposing and developing a National Institute for Forensic Toxicology in Ireland 
      transformation through education.
AB  - Toxicology for coroners is an important minority service whose quality is central
      to the validity and integrity of the death certification system.
      Multidisciplinary case conferences are routine practice in the major medical
      specialties. In conventional practice for the coroners' courts, the dissecting
      pathologist is often relied upon to interpret toxicological data usually without
      specialist training. In Ireland the service is fragmented and there is at present
      no medically trained toxicologist directly involved in the direction or reporting
      of cases even where multiple drugs are found in blood at various levels and drug
      drug interaction may be possible or likely. To encourage both medical
      professionals and political administration to confront the issues, the education
      literature on action research and critical incident methodology is reviewed to
      develop a strategy for change in this service. An example of action research
      being applied to medicine is used as an indicator that an action research
      template could be used to advocate for a new National Institute for Forensic
      Toxicology in Ireland. The main participant groups are identified and the
      development cycle outlined. 

PMID- 23961423
TI  - Biodiversity baseline of the French Guiana spider fauna.
AB  - The need for an updated list of spiders found in French Guiana rose recently due
      to many upcoming studies planned. In this paper, we list spiders from French
      Guiana from existing literature (with corrected nomenclature when necessary) and
      from 2142 spiders sampled in 12 sites for this baseline study. Three hundred and
      sixty four validated species names of spider were found in the literature and
      previous authors' works. Additional sampling, conducted for this study added
      another 89 identified species and 62 other species with only a genus name for
      now. The total species of spiders sampled in French Guiana is currently 515. Many
      other Morphospecies were found but not described as species yet. An accumulation
      curve was drawn with seven of the sampling sites and shows no plateau yet.
      Therefore, the number of species inhabiting French Guiana cannot yet be
      determined. As the very large number of singletons found in the collected
      materials suggests, the accumulation curve indicates nevertheless that more
      sampling is necessary to discover the many unknown spider species living in
      French Guiana, with a focus on specific periods (dry season and wet season) and
      on specific and poorly studied habitats such as canopy, inselberg and cambrouze
      (local bamboo monospecific forest). 

PMID- 23961424
TI  - Characterization of leptospira isolates from animals and humans: phylogenetic
      analysis identifies the prevalence of intermediate species in India.
AB  - In this study, 191 culture isolates were recovered from suspected samples of
      animals and humans in Ellinghausen McCullough Johnson and Harris (EMJH) medium
      and assessed for its morphological features by dark field microscopy. Extracted
      DNA from individual culture was subjected to different PCR assays for
      identification and characterization of leptospira. Out of 99 positive leptospira
      cultures, 52 pathogenic leptospira isolates were characterized at species level
      by using partial RNA polymerase beta-subunit (rpoB) gene sequences. Phylogenetic
      analysis of the nucleotide sequences revealed that 30, 8, and 14 isolates belong
      to L. borgpetersenii / L. interrogans, L. kirschneri, and Leptospira intermediate
      species, respectively. Based on analysis of 99 leptospira isolates, the prevalent
      Leptospira species were L. borgpetersenii or L. interrogans (30.30%), L.
      kirschneri (8%) and Leptospira intermediate species (14.14%) in animals and
      humans. To the best of authors knowledge, this is the first study to use rpoB
      gene nucleotide sequence based phylogenetic analysis to identify/detect
      Leptospira intermediate species (L. wolffii) in animals and humans in India.
      Hence, the prevalence of this species will surely emphasize the importance of
      consideration of Leptospira intermediate species and formulate a way for further
      studies especially in understanding the newly emerging Leptospira in animals and
      humans and to combat the problem associated with the disease conditions. 

PMID- 23961425
TI  - Antibacterial activities of the methanol extracts of seven Cameroonian dietary
      plants against bacteria expressing MDR phenotypes.
AB  - The morbidity and mortality caused by bacterial infections significantly
      increased with resistance to commonly used antibiotics. This is partially due to
      the activation of efflux pumps in Gram-negative bacteria. The present work
      designed to assess the in vitro antibacterial activities of seven Cameroonian
      dietary plants (Sesamum indicum, Sesamum radiatum, Cinnamomum zeylanicum,
      Corchous olitorius, Cyperus esculentus, Adansonia digitata, Aframomum
      kayserianum), against multidrug resistant (MDR) Gram-negative bacteria over
      expressing active efflux pumps. The standard phytochemical methods were used to
      detect the main classes of secondary metabolites in the extracts. The
      antibacterial activities of the studied extracts in the absence or presence of an
      efflux pump inhibitor (PAbetaN) were evaluated using liquid microbroth dilution
      method. The results obtained indicated that apart from the extract of C.
      esculentus, all other samples contained alkaloids, phenols and polyphenols
      meanwhile other classes of chemicals were selectively present. The studied
      extracts displayed antibacterial activities with minimal inhibitory
      concentrations (MICs) values ranged from 64 to 1024 MUg/mL on the majority of the
      27 tested microbial strains. The extract of S. indicum was active against 77.77%
      of the tested microorganisms whilst the lowest MIC value (64 MUg/mL) was recorded
      with that of A. kayserianum against E. aerogenes EA294. The results of the
      present work provide baseline information on the possible used of the tested
      Cameroonian dietary plants in the treatment of bacterial infections including
      multi-drug resistant phenotypes. 

PMID- 23961426
TI  - Barriers and challenges in integration of anthroposophic medicine in supportive
      breast cancer care.
AB  - In the last decade, more and more oncology centers are challenged with
      complementary medicine (CM) integration within supportive breast cancer care.
      Quality of life (QOL) improvement and attenuation of oncology treatment side
      effects are the core objectives of integrative CM programs in cancer care. Yet,
      limited research is available on the use of specific CM modalities in an
      integrative setting and on cancer patients' compliance with CM consultation.
      Studies are especially warranted to view the clinical application of researched
      CM modalities, such as anthroposophic medicine (AM), a unique CM modality
      oriented to cancer supportive care. Our objective was to characterize
      consultation patterns provided by physicians trained in CM following oncology
      health-care practitioners' referral of patients receiving chemotherapy. We aimed
      to identify characteristics of patients who consulted with AM and to explore
      patients' compliance to AM treatment. Of the 341 patients consulted with
      integrative physicians, 138 were diagnosed with breast cancer. Following
      integrative physician consultation, 56 patients were advised about AM treatment
      and 285 about other CM modalities. Logistic multivariate regression model found
      that, compared with patients receiving non-anthroposophic CM, the AM group had
      significantly greater rates of previous CM use [EXP(B) = 3.25, 95% C.I. 1.64
      6.29, p = 0.001] and higher rates of cancer recurrence at baseline (p = 0.038).
      Most AM users (71.4%) used a single AM modality, such as mistletoe (viscum album)
      injections, oral AM supplements, or music therapy. Compliance with AM modalities
      following physician recommendation ranged from 44% to 71% of patients. We
      conclude that AM treatment provided within the integrative oncology setting is
      feasible based on compliance assessment. Other studies are warranted to explore
      the effectiveness of AM in improving patients' QOL during chemotherapy. 

PMID- 23961427
TI  - Obstacles encountered during transradial angiography from after Radial Artery
      puncture to the aortic arch.
AB  - OBJECTIVE: To elucidate the key points for safe performance of transradial
      angiography. CONCLUSIONS: Transradial angiography can be performed safely if
      attention is paid to the following points from after radial artery puncture to
      reaching the aortic arch: resistance during guide wire operation for sheath
      insertion after puncture; confirmation of the superficial brachial artery; guide
      wire resistance while guiding the catheter to the aortic arch; and aortic arch
      anomalies.

PMID- 23961429
TI  - The efficacy of contrast protocol in hepatic dynamic computed tomography:
      multicenter prospective study in community hospitals.
AB  - PURPOSE: To investigate four different contrast protocols to detect hypervascular
      hepatocellular carcinoma (HCC) most adaptable for patients at any body weight
      (BW) in clinical practice. MATERIALS AND METHODS: A post-marketing surveillance
      of liver dynamic CT was prospectively performed by four different protocols in
      415 patients: Protocol-A, BW-tailored dose of contrast media (CM: iohexol 300
      mgI/mL), fixed injection duration (30s), fixed scan timing at arterial phase
      (AP); Protocol-B, BW-tailored dose of CM, fixed injection duration (30s), by
      bolus tracking; Protocol-C, BW-tailored dose of CM, fixed injection flow rate, by
      bolus tracking; Protocol-D, 100 mL constant of CM at any BW, fixed scan timing.
      Scan timing and tumor conspicuity at AP was scored qualitatively. The
      quantitative CT values of aorta and tumor liver contrast (TLC) were obtained.
      RESULTS: The qualitative rate assessed "good" as scan timing of AP in Protocol-C
      was significantly lower than those in Protocols A and D (difference:16.6%, 17.4%,
      P = 0.0069, P = 0.0140, respectively). Scatter plot of Protocol-D (R(2) = 0.1283)
      at AP showed significant inverse relationship between TLC and BW (P =0.0053),
      although not significant in Protocols A, B, C. CONCLUSION: In patients with
      higher BW, protocols of BW-tailored dose of CM and/or fixed injection duration
      have no dependence on BW to diagnose hypervascular HCCs.

PMID- 23961430
TI  - Individual differences effects on the psychological refractory period.
AB  - The goal of this study was to assess the impact of individual neuropsychological
      differences on the ability to share attention between concurrent tasks.
      Participants (n = 20) were trained on six single task practice sessions and dual
      task was assessed with reaction time performance on a psychological refractory
      period (PRP) paradigm. Neuropsychological test scores were also acquired.
      Furthermore, one of the known variables that can influence performances on
      neuropsychological tests is gender, which was added as a potential predictor.
      Results show that the small PRP group was associated with better performances in
      processing speed, inhibition, flexibility and working memory on
      neuropsychological tests. Gender also had an impact on the PRP, males having a
      lower PRP than females. A multiple regression was performed to determine which
      variables explained the most PRP duration, which showed that 49.1% of the
      variance of the PRP length could be explained by gender, reaction times of the
      PRP practice trials at the sixth session, the denomination and flexibility
      conditions of the Modified Stroop Task as well as results on the Symbol Search
      Test. Gender was the variable that explained the PRP variance the most (23%).
      Processing speed also seemed to be a great determinant of the PRP as well as the
      ability to alternate between task-sets as assessed by the Flexibility condition
      of the Modified Stroop Task. Thus, this study reveals that good performances on
      certain neuropsychological tests could predict one's ease to manage two tasks
      simultaneously with a higher chance for males to perform better. 

PMID- 23961428
TI  - Is Age-targeted full-field digital mammography screening cost-effective in
      emerging countries? A micro simulation model.
AB  - OBJECTIVE: The present paper estimates the cost-effectiveness of population-based
      breast cancer (BC) screening strategies in Brazil for women under 50 years from
      the perspective of the Brazilian public health system. METHODS: A Markov model,
      simulating the natural history of female BC sufferers in Brazil, was developed.
      This model compares the lifetime effects, costs, and cost-effectiveness of seven
      BC screening strategies in women between 40 to 49 years: (A) usual care; (B)
      annual screen-film mammography (SFM); (C) SFM every 2 years; (D) annual full
      field digital mammography (FFDM); (E) FFDM every 2 years; and (F and G) age
      targeted options, with FFDM annually until 49 years and SFM annually (or
      biannually) from 50 to 69 years. RESULTS: Adopting SFM every 2 years (Strategy C)
      was found to be slightly more costly but also more effective in terms of quality
      adjusted life years (QALYs), yielding an incremental cost-effectiveness ratio
      (ICER) of R$ 1,509 per QALY gained. Annual SFM (Strategy B) was the next best
      option at an additional R$ 13,131 per QALY gained. FFDM annual screening
      (Strategy E) was dominated by Strategy F, the age-targeted option. For younger
      women, the age-based strategy had an ICER of R$ 30,520 per QALY gained. In the
      sensitivity analysis, the ICERs ranged from R$ 15,300 to R$ 257,899 in different
      regions of the country, depending on BC incidence, population age distribution,
      and mammography coverage. CONCLUSIONS: SFM every 2 years for all women starting
      between the ages of 40 and 49 would be a cost-effective strategy. Taking into
      account regional specificities, age-targeted FFDM is one option to improve the
      outcomes of BC patients in an emerging country.

PMID- 23961431
TI  - Antimicrobial activity of amazonian medicinal plants.
AB  - OBJECTIVES: The aqueous extracts of currently utilized Amazonian medicinal plants
      were assayed in vitro searching for antimicrobial activity against human and
      animal pathogenic microorganisms. METHODS: Medium resuspended lyophilized aqueous
      extracts of different organs of Amazonian medicinal plants were assayed by in
      vitro screening for antimicrobial activity. ATCC and standardized microorganisms
      obtained from Oswaldo Cruz Foundation/Brazil were individually and homogeneously
      grown in agar plate, and holes previously perforated in the gel were filled with
      diluted plant aqueous extracts. Inhibition halos were evaluated and controlled by
      the use of the fluoroquinolone ciprofloxacin. RESULTS: The Amazonian medicinal
      plants, Hymenelobium petraeum showed inhibitory activity over Staphylococcus
      aureus, Enterococcus faecalis, Salmonella enterica serovar Typhi, Acinetobacter
      baumannii and Candida albicans, while Vatairea guianensis and Symphonia
      globulifera presented inhibitory activity exclusively for Staphylococcus aureus.
      Also, Ptychopetalum olacoides and Pentaclethra macroloba inhibited the growth of
      Klebsiella ozaenae and Acinetobacter baumannii. CONCLUSION: The aqueous botanic
      extracts that showed activity against microroganisms of ATTC and Osvaldo Cruz
      strains had at least 40% of antimicrobial activity when compared to halo
      inhibition produced by the commercial antibiotic ciprofloxacin utilized as a
      control. Of all plants extracts assayed, the Hymenelobium petraeum had the best
      performance, sometimes exhibiting higher activity than ciprofloxacin. It is not
      well-defined by the physicians the exact indication of the majority of medicinal
      plants in the Amazon area in Brazil. Natives utilize the plants according to
      their symptoms, based on the traditional knowledge transmitted orally from
      generation to generation, among Amerindians, Afrodescendents and ethnic mixed
      populations. A significant number of Amazonian medicinal plants are totally
      unknown related to their medicinal properties including mechanism of action and
      therapeutic effects, as very few information is reported in the scientific
      literature. A tiny amount of data is presented, as the preliminary antimicrobial
      properties of the medicinal plants here accessed, under the urgent necessity of
      new antibiotics in the market and in face of the increased resistance of
      infectious microorganisms to antimicrobials.

PMID- 23961432
TI  - Copper content of staple seeds and grains grown in Kanam local government area,
      Nigeria.
AB  - Copper is a trace mineral that plays an important role in human metabolism,
      largely because it allows many critical enzymes to function properly. Little is
      known of copper content of Nigerian foods. In this paper, copper contents of
      several typical Nigerian foods were determined. The samples were collected from
      Kanam of Plateau State in central region of Nigeria. The samples were wet-ashed
      according to the protocol of Hill et al. (Anal Chem 55:2340-2342,
      1986).Concentrations of copper in the samples was determined using inductively
      coupled-mass spectrophotometry. There is, for each crop, a wide variation in
      copper content. The highest copper content was found in cowpea, Vigna unguiculata
      (16.95 MUg/g of dry weight). Lowest copper content was found in white maize and
      in yellow maize (Zea mays), with values 1.23 MUg/g and 1.38 MUg/g of dry weights,
      respectively. Other foods, such as white sorghum, red sorghum (Sorghum bicolor),
      millet (Pennisetum glaucum), and groundnuts (Arachis hypogea) had copper contents
      varying from 2.22 to 11.81 MUg/g. These values are well below the supplemental
      values of 50 mg/day that could interfere with zinc absorption. Thus, among the
      staple foodstuffs of the areas sampled, cowpea appears to be the richest source
      of dietary copper followed by groundnut while the two maize varieties are the
      poorest. 

PMID- 23961433
TI  - Blastocystis: Status of its pathogenicity.

PMID- 23961435
TI  - Ethics of involving animals in research.
AB  - Use of animals in research is a highly debatable topic. Though their use has led
      to several discoveries and understanding of many aspects of science but their use
      in certain sectors needs to be justified. There are national and international
      laws which govern the use of animals in research, all of which are based on the
      principles of the 4Rs - replacement, reduction and refinement and the
      rehabilitation of the use of animals in research. It is mandatory that all
      institutions involved in animal research develop and abide by the ethical review
      processes which promote good animal welfare practices by ensuring that the use of
      animals at the designated establishment is justified. With the availability of
      many alternatives, the lives of many animals can now be secure. 

PMID- 23961434
TI  - Human dirofilariasis: An emerging zoonosis.

PMID- 23961436
TI  - Current laboratory diagnosis of opportunistic enteric parasites in human
      immunodeficiency virus-infected patients.
AB  - Diarrhea is a major cause of morbidity and mortality in human immunodeficiency
      virus (HIV)-infected individuals. Opportunistic enteric parasitic infections are
      encountered in 30-60% of HIV seropositive patients in developed countries and in
      90% of patients in developing countries. Once the CD4(+) cell count drops below
      200 cells/MUl, patients are considered to have developed acquired
      immunodeficiency syndrome (AIDS), with the risk of an AIDS-defining illness or
      opportunistic infection significantly increasing. Opportunistic enteric parasites
      encountered in these patients are Cryptosporidium, Isospora, Cyclospora, and
      microsporidia; as well as those more commonly associated with gastrointestinal
      disease, for example, Giardia intestinalis, Entamoeba histolytica, Strongyloides
      stercoralis, and also rarely Balantidium coli. In view of AIDS explosion in
      India, opportunistic enteric parasites are becoming increasingly important and it
      has to be identified properly. Apart from wet mounts, concentration methods for
      stool samples and special staining techniques for identification of these
      parasites, commercially available fecal immunoassays are widely available for the
      majority of enteric protozoa. Molecular methods such as polymerase chain reaction
      (PCR), PCR-restriction fragment length polymorphism, flow cytometry, and sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), have also come in
      the pipeline for early diagnosis of these infections. Proper disposal of the
      feces to prevent contamination of the soil and water, boiling/filtering drinking
      water along with improved personal hygiene might go a long way in preventing
      these enteric parasitic infections. 

PMID- 23961437
TI  - Blastocystis: Taxonomy, biology and virulence.
AB  - The unicellular protist Blastocystis has long been an unsolved puzzle for
      taxonomists, microbiologists and clinicians. Over the years, the organism has
      been bounced on and off the different branches of the tree of life due the
      possession of unique phenotypic characters intermediary to different organisms.
      The organism is polymorphic with only few of forms such as vacuolar, granular,
      amoeboid, and the cyst form being commonly known. However it could exist in other
      forms much more frequently than the widely known forms which could be missed by
      the unaware observer. Certain older concepts in the life cycle of Blastocystis
      although has been proven wrong are still being followed in various textbooks and
      other trustworthy internet sources. The causal role of Blastocystis in human
      disease has long been a subject of controversy. It is widely believed that
      certain subtypes of the organism are virulent. But this is not so as other
      factors are also involved in the clinical outcome of the infection. In these
      contexts, this review intends to shed light on the past misconceptions and the
      recent findings on the taxonomy, biology and the virulence of this organism. 

PMID- 23961439
TI  - Blastocystis: Consensus of treatment and controversies.
AB  - Blastocystis is a highly controversial protozoan parasite. It has been variably
      regarded as a commensal and pathogen. Scientists have for decades wondered
      whether it is truly an enteropathogen and if it is observed in symptomatic
      patients whether treatment is required because patient recovery and improvement
      has been noted even without any treatment. Though associated with self-limiting
      infection, treatment is warranted in many patients due to persistence of
      symptoms. This particularly holds true for children and adults who are immuno
      compromised. Several drugs have been used to treat Blastocystis but each one of
      them has produced widely variable rates of clinical cure and eradication of the
      parasite from the feces. Based on the studies carried out in vitro and clinical
      responses obtained in patients, metronidazole appears to be the most effective
      drug for Blastocystis infection. However, the therapy is complicated due to
      different dosages and regimens adopted and the unresponsiveness to treatment
      observed in several sections of the population studied. Recently, the finding of
      different subsets of Blastocystis exhibiting resistance to metronidazole and
      associated with variable degrees of symptoms has underscored the importance of
      typing the subsets of the parasite in order to foretell the clinical response and
      the need to treat. Till date, the mode of action of the drugs used and the
      mechanism of resistance is not entirely known and is a topic of speculation.
      Other drugs with anti Blastocystis activity and used in therapy includes
      trimethoprim sulfamethoxazole and nitazoxanide. Several other compounds have also
      been evaluated for the treatment either alone or in combination with the first or
      second line drugs. A lot of interest has also been generated on the role of
      probiotics particularly Saccharomyces boularrdii and other natural food compounds
      on eradication of the parasite. This review provides a comprehensive overview of
      antimicrobials used to target Blastocystis and discusses the issues pertaining to
      drug resistance, treatment failure, reinfection, and the current views on
      treatment modalities. 

PMID- 23961438
TI  - Blastocystis: Genetic diversity and molecular methods for diagnosis and
      epidemiology.
AB  - Blastocystis, an unusual anaerobic, single-celled stramenopile, is a remarkably
      successful intestinal parasite of a vast array of host species including humans.
      Fecal Deoxyribonucleic acid (DNA) analysis by nucleic-acid based methods in
      particular has led to significant advances in Blastocystis diagnostics and
      research over the past few years enabling accurate identification of carriers and
      molecular characterization by high discriminatory power. Moreover, Blastocystis
      comprises a multitude of subtypes (STs) (arguably species) many of which have
      been identified only recently and molecular epidemiological studies have revealed
      a significant difference in the distribution of STs across host species and
      geographical regions. Having a cosmopolitan distribution, the parasite is a
      common laboratory finding in the stools of individuals with and without
      intestinal symptoms across the entire globe and while the parasite remains
      extremely difficult to eradicate and isolate in culture, appropriate molecular
      tools are now available to resolve important questions such as whether the
      clinical outcome of colonization is linked to ST and whether Blastocystis is
      transmitted zoonotically. This review summarizes some of the recent advances in
      the molecular diagnosis of Blastocystis and gives an introduction to Blastocystis
      STs, including a recommendation of subtyping methodology based on recent data and
      method comparisons. A few suggestions for future directions and research areas
      are given in the light of relevant technological advances and the availability of
      mitochondrial and nuclear genomes. 

PMID- 23961440
TI  - The merits of designed ELISA avidity kit in detection of Toxoplasma gondii IgG
      antibody in laboratory conditions.
AB  - BACKGROUND: Toxoplasmosis is a parasitic disease which may cause some laboratory
      symptoms in infected individuals. One of the main ways to transmit this organism
      is placenta to the fetus pathway. If this transmission occurs in the 3(rd) month
      of pregnancy, the abortion, central nerve system and ocular disorder will happen.
      Because of this issue, the precise technique for the detection of Toxoplasma
      antibodies such as immunoglobulin G (IgG) and immunoglobulin M IgM are important,
      as they contain ELISA and ELISA avidity. MATERIALS AND METHODS: In this survey,
      the main samples are serum and amniotic fluid that were collected from 48
      pregnant women infected with Toxoplasma gondii in Shariaty hospital. This survey
      is attempted to design ELISA avidity kit in Tarbiat Modates University. RESULTS:
      The results from this survey show that, in these total pregnant women the
      infection by T. gondii has occurred and many of them are infected currently.
      CONCLUSIONS: In the simple ELISA technique, the only antibody that can be
      detected precisely is IgM; however, using this technique the IgG antibody can
      also be detected. In this new technique or ELISA avidity, in addition to
      detection of IgG antibody against T. gondii, the month of transmission of
      Toxoplasma is also interpreted.

PMID- 23961441
TI  - Immunodiagnosis of fascioliasis using sandwich enzyme-linked immunosorbent assay
      for detection of Fasciola gigantica paramyosin antigen.
AB  - BACKGROUND: Many immunological techniques have been developed over years using
      the different Fasciola antigens for diagnosis of parasitic infection and to
      replace the parasitological techniques, which are time consuming and usually lack
      sensitivity and reproducibility. MATERIALS AND METHODS: In this study, Fasciola
      gigantica paramyosin (Pmy) antigen was early detected in cattle sera using
      sandwich enzyme-linked immunosorbent assay (ELISA), to evaluate the Pmy antigen
      performance in diagnosis. This work was conducted on 135 cattle blood samples,
      which were classified according to parasitological investigation into, healthy
      control (30), fascioliasis (75), and other parasites (30) groups. RESULTS: The
      sensitivity of Sandwich ELISA was 97.33%, and the specificity was 95%, in
      comparison with parasitological examination, which recorded 66.66% sensitivity
      and 100% specificity, respectively. CONCLUSIONS: It was clear that the native F.
      gigantica Pmy is considered as a powerful antigen in early immunodiagnosis of
      fascioliasis, using a highly sensitive and specific sandwich ELISA technique.

PMID- 23961442
TI  - Clinico-laboratory profile of severe Plasmodium vivax malaria in a tertiary care
      centre in Kolkata.
AB  - BACKGROUND: Vivax malaria is the most widely distributed human malaria and is
      responsible for up to 400 million infections every year. Recently, it has become
      evident that Plasmodium vivax monoinfection could also result in multiple organ
      dysfunction and severe life-threatening disease as seen in Plasmodium falciparum
      infection. MATERIALS AND METHODS: The aim of this study was to note the different
      clinical and biochemical profiles of adult patients with the severe vivax malaria
      with regards to complications and outcome. This was a prospective observational
      study carried out at a tertiary care hospital in Kolkata over 9 month's period.
      Detailed history and examination findings were noted in all patients. Their
      clinical presentations, complications, course in ward until discharge or death
      was noted. RESULTS: A total of 900 cases of vivax malaria were included in the
      study. Severe disease was present in 200 (22.2%) cases of malaria. There were 108
      (54%) patients with single complication (SC) and 92 (46%) patients with the
      multiple complications (MC). Patients with SC had jaundice (48.1%) followed by
      cerebral involvement (25.9%), renal failure (7.4%), and pulmonary involvement
      (3.7%). The MC was found in various combinations and the majority (47.8%) had
      constellation of two different complications. The mortality rate of patients with
      the SC and MC was 7.4% and 34.8%. The overall mortality observed in severe vivax
      malaria was 20% (40/200). CONCLUSIONS: In recent years, the clinical pattern of
      vivax malaria has changed. Severe vivax malaria is now very common with
      increasing mortality. Not only the number, but also the type of complication
      influences the outcome of complicated malaria.

PMID- 23961443
TI  - Study of thrombocytopenia in patients of malaria.
AB  - BACKGROUND: Malaria is a Protozoal disease caused by infection with parasites of
      the genus Plasmodium and transmitted to man by certain species of infected female
      Anopheline mosquito. In 2008 there were 1.52 million cases of malaria in India,
      out of which 0.76 million case of Plasmodium falciparum, comprising 50% of total
      malaria cases. There were 924 deaths from malaria. Hematological abnormalities
      have been observed in patients with malaria, with anemia, and thrombocytopenia
      being the most common. MATERIALS AND METHODS: We conducted this study to find out
      the frequency and the degree of thrombocytopenia in patients with malaria. In our
      study, 230 patients with malaria positive were investigated with platelet count.
      RESULTS: In the study group of 230 patients: 130 (56.51%) were positive for
      Plasmodium vivax, 90 (39.13%) were positive for P. falciparum and 10 (4.34%) had
      mixed infection with both P. vivax and P. falciparum. Out of 130 cases detected
      with vivax malaria, 100 cases had thrombocytopenia. Out of 90 cases detected with
      falciparum malaria, 70 cases had thrombocytopenia. Among 10 cases of mixed
      infection, 9 cases had thrombocytopenia. CONCLUSIONS: Presence of
      thrombocytopenia in a patient with acute febrile illness in the tropics increases
      the possibility of malaria. The above finding can have therapeutic implications
      in context of avoiding unnecessary platelet infusion in malaria patients.

PMID- 23961444
TI  - Seroprevalence of toxoplasmosis in antenatal women with bad obstetric history.
AB  - BACKGROUND: The occurrence of fetal death is one of the tragedies that confront
      the physician providing obstetric care. Among the various agents associated with
      infections of pregnancy, viruses are the most important followed by bacteria and
      protozoa. Among protozoal infections in pregnancy, toxoplasmosis is reported to
      have a high incidence, sometimes causing fetal death. The study was intended to
      observe the seroprevalence of Toxoplasmosis in pregnant women presenting with bad
      obstetric history (BOH). MATERIALS AND METHODS: A total of 92 antenatal women
      were included in the study (80 in the study group and 12 in control group). The
      study group comprised of antenatal women with BOH in the age group of 20-35
      years. Antenatal women with Rh incompatibility, pregnancy induced hypertension,
      diabetes mellitus, renal disorders and syphilis were not included in the study.
      The control group included women in reproductive age group without BOH. All the
      samples were screened by enzyme linked immuno sorbent assay (ELISA) for
      Toxoplasma specific Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibodies.
      RESULTS: Of the 80 antenatal women in the study group, 36 (45%) were seropositive
      for Toxoplasma specific IgG antibodies (P < 0.005), 16 (20%) were seropositive
      for Toxoplasma specific IgM antibodies (P < 0.005) and 8 (10%) were seropositive
      for both IgG and IgM antibodies (P < 0.005). Various predisposing factors for
      acquiring Toxoplasmosis such as contact with cats, contact with soil, food
      habits, illiteracy, socio-economic status and residential status were also
      studied. CONCLUSIONS: We conclude that toxoplasmosis during pregnancy causes
      congenital fetal infection with possible fetal loss. ELISA was found to be a
      sensitive serological test for diagnosis of Toxoplasmosis in pregnant women with
      BOH. Major cause of fetal loss in BOH cases in the study group was abortion.

PMID- 23961445
TI  - Mass drug administration for elimination of lymphatic filariasis: Recent
      experiences from a district of West Bengal, India.
AB  - BACKGROUND: Annual mass drug administration (MDA) with diethyl carbamazine (DEC)
      and Albendazole is the most cost-effective strategy to control lymphatic
      filariasis (LF). MATERIALS AND METHODS: The aim of the present study was to
      assess the coverage and the compliance of MDA, to elicit factors that influenced
      compliance, to document side-effects reported and to assess the awareness of the
      community regarding the disease and MDA program in Bankura district, West Bengal
      after 2012 round of MDA. Multistage cluster sampling method was adopted. Total
      four clusters; three villages and one urban municipality ward were selected. In
      each cluster, minimum 30 families were randomly selected and the head or any
      responsible family member was interviewed using a pre-designed, pre-tested
      schedule after taking written informed consent. Data were compiled and analyzed
      using SPSS 19.0. RESULTS: Total eligible population was 683 among which 98.8%
      received both the drugs. About 5% of the recipients took none of the drugs. More
      than two-thirds of the families took unsupervised dose. Drug compliance rate was
      significantly lower in urban (90.7%) than in the rural clusters (95.7%) (z =
      2.46, P < 0.05). Effective coverage rate was significantly lower in urban than in
      the rural clusters (87.4% vs. 95.3%; z = 3.57, P < 0.01). Coverage compliance gap
      was higher in urban (5.7%) than in rural cluster (3.9%). Fear of side-effects was
      the main reason for non-compliance. Reported side-effects were few, mild, and
      transient. Around 60% of the surveyed families were aware about the MDA program
      whereas, 67% of them heard about LF. Only 41% families were provided information,
      education, and communication in last 15 days before MDA. Major sources of
      information for the surveyed families were leaflets (20.3%) and poster (9.8%).
      CONCLUSIONS: Widespread rural urban variation in performance status, poor social
      mobilization activities, lack of supervised dosing, and lack of knowledge of the
      community about the disease and the program are the major areas of concern.

PMID- 23961446
TI  - Use of polymerase chain reaction: Restriction fragment length polymorphism to
      detect acaricidal resistance to synthetic pyrethroids in Boophilus microplus
      ticks of South India.
AB  - BACKGROUND: Boophilus microplus is an important ectoparasite of livestock. Apart
      from transmitting diseases, heavy tick burden can decrease production and damage
      hides. The synthetic pyrethroids which are advantageous over other acaricides for
      treatment of this infestation are now losing their efficacy due to development of
      resistant strains of ticks. MATERIALS AND METHODS: Boophilus microplus ticks with
      a previous history of acaricidal treatment especially synthetic pyrethroids (SP)
      such as cypermethrin, deltamethrin and flumethrin were randomly collected from
      different pockets of four Southern States of India namely Tamil Nadu, Kerala,
      Karnataka, Andhra Pradesh, and Puducherry from cattle. Deoxyribonucleic acid
      extracted from pooled adult B. microplus tick from each State was subjected to
      polymerase chain reaction-restriction fragment length polymorphism to detect
      point mutation in carboxyl esterase gene. RESULTS: A product size of 372 bp was
      obtained for cattle tick samples collected from all over Southern States of
      India. CONCLUSIONS: B. microplus ticks found in Southern part of India are not
      resistant to commonly used SP.

PMID- 23961447
TI  - Human subcutaneous dirofilariasis in Assam.
AB  - Human subcutaneous dirofilariasis is caused by filarial worms of the genus
      Dirofilaria. The parasites are transmitted to man by mosquitoes. We report three
      cases of human subcutaneous dirofilarias caused by Dirofilaria repens from
      Dibrugarh, Assam, north east India. The cases presented as subcutaneous nodules,
      on the chest, cheek and the anterior abdominal wall. Noting the frequency of the
      cases reported within 6 months, it is emphasized that subcutaneous dirofilariasis
      is a potentially emerging zoonosis in Assam and should be included in the
      differential diagnosis of patients presenting with subcutaneous nodules in Assam.

PMID- 23961448
TI  - Post-partum pyogenic abscess containing Ascaris lumbricoides.
AB  - We report an unusual case of multiple pyogenic liver abscesses containing
      Ascariasis lumbricoides in a 35-year-old post-partum female who had delivered 1
      month back. Open drainage of liver abscess along with liver worm was done.
      Patient did well post-operatively. 

PMID- 23961449
TI  - Intraocular gnathostomiasis from coastal part of Maharashtra.
AB  - Intraocular infestation by live Gnathostoma spinigerum is a rare occurrence in
      humans. Most of the published reports are from South-East Asia. We report a case
      of ocular gnathostomiasis from Western Maharashtra, where the worm was removed
      live from the anterior chamber of the left eye. Identification of the worm was
      confirmed by light microscopy. 

PMID- 23961450
TI  - Chronic diarrhea due to Cyclospora spp. infection.

PMID- 23961452
TI  - An interview with Dr. M. C. Agrawal.

PMID- 23961451
TI  - Keratitis due to Staphylococcus aureus and Acanthamoeba species following injury.

PMID- 23961453
TI  - What's New in Critical Illness and Injury Science? The challenge of verifying
      tracheal airway placement: Solving the puzzle one piece at a time.

PMID- 23961454
TI  - Intubation of patients with angioedema: A retrospective study of different
      methods over three year period.
AB  - BACKGROUND: Angioedema (AE) is edema of the skin, subcutaneous tissue and/or
      submucosal tissues, resulting from extravasation of intravascular fluid. Swelling
      of the supraglottic mucosa can lead to airway obstruction with consequent
      hypoxia, brain damage and death. To date, fiberoptic bronchoscope (FOB)
      intubation of the spontaneously breathing patient is the preferred method for an
      anticipated difficult intubation. However, other alternative devices can be
      utilized to intubate angioedema successfully. MATERIALS AND METHODS: A
      retrospective chart review was performed over a three-year period (2008-2010) of
      all patients with angioedema that required airway intervention. We hypothesized
      that fiberoptic intubation would have a higher success rate for intubation
      attempts; however, would take longer to perform when compared to
      videolaryngoscopic (VL) intubation. Outcomes for FOB versus VL intubations were
      reviewed, along with alternative miscellaneous methods of tracheal intubation in
      the setting of angioedema. RESULTS: Thirty-three patients were grouped, according
      to the chosen method of intubation into FOB (n=12), VL (n=11), and miscellaneous
      (n=10) groups. No significant difference was found in first intubation attempts
      or number of intubation attempts between the three groups. Duration of time to
      perform successful intubation revealed a significantly shorter intubation time
      (P<0.05) in the VL group (6.9+/-0.9 min) and miscellaneous group (9.1+/-2.0 min)
      than that of the FOB group (10.4+/-0.7 min). CONCLUSION: This retrospective
      review of intubation methods showed that VL could be performed faster than FOB
      without an increase in adverse events.

PMID- 23961455
TI  - Secondary confirmation of endotracheal tube position by diaphragm motion in right
      subcostal ultrasound view.
AB  - AIMS: To assess the sensitivity and specificity of right subcostal ultrasound
      view to confirm correct endotracheal tube intubation (ETT). MATERIALS AND
      METHODS: In this prospective study, apneic or paralyzed patients who had an
      indication of intubation were selected. Intubation and ventilation with bag were
      performed by the skilled third-year emergency medicine residents. The residents,
      following a brief training course of ultrasonography, interpreted the diaphragm
      motion, and identified either esophageal or tracheal intubation. The confirmation
      of ETT placement was done by the sonographer. Sensitivity, specificity, positive
      predictive value, negative predictive value, and accuracy were calculated for
      tracheal versus esophageal intubation. RESULTS: A total of 57 patients aged 59 +/
      5 who underwent ETT insertion were studied. Thirty-four of them were male (60%).
      Ultrasound correctly identified 11 out of 12 esophageal intubations for a
      sensitivity of 92% (95% CI = 62-100), but misidentified one esophageal intubation
      as tracheal. Sonographers correctly identified 43 out of 45 (96%) tracheal
      intubations for a specificity of 96% (95% CI = 85-99), but misdiagnosed two
      tracheal intubations as esophageal. CONCLUSIONS: This study suggests that
      diaphragm motion in right subcostal ultrasound view is an effective adjunct to
      diagnose ETT place in patients undergoing intubation in emergency department.

PMID- 23961456
TI  - Non-operative management of blunt liver trauma in a level II trauma hospital in
      Saudi Arabia.
AB  - BACKGROUND: To evaluate our experience with non-operative management of blunt
      liver trauma at a level II trauma hospital in the Kingdom of Saudi Arabia.
      MATERIALS AND METHODS: We prospectively evaluated 56 patients treated for blunt
      liver trauma at our hospital over a 4-year period (April 2008 to April 2012).
      Patients who were hemodynamically stable [non-operative group I (NOP)] were
      treated conservatively in the intensive or intermediate care unit (ICU or IMCU).
      Patients who were hemodynamically unstable or needed laparotomy for other
      injuries were treated by urgent laparotomy [operative group II (OP)]. All NOP
      group patients had computed tomography (CT) of the abdomen with oral and
      intravenous contrast. Injuries grades were classified according to the American
      Association for the Surgery of Trauma (AAST). Follow-up CT of the abdomen was
      performed after 2 weeks in some cases. RESULTS: A total of 56 patients were
      treated over a 4-year period. Twenty patients (35.7%) were treated by immediate
      surgery. NOP group of 36 patients (64.3%) were managed in the ICU by close
      monitoring. Surgically treated group had more patients with complex liver injury
      (90% versus 58.3%), required more units of blood (6.05 versus 1.5), but had a
      longer hospital stay (16.6 days versus 15.1 days). None of the patients from the
      non-operated group developed complications nor did they need operation. The only
      mortality (in two patients) was in the operated group. CONCLUSION: The NOP
      treatment is a safe and effective method in the management of hemodynamically
      stable patients with blunt liver trauma. The NOP treatment should be the
      treatment of choice in such patients whenever CT and ICU facilities are
      available.

PMID- 23961457
TI  - Frequency of hypoxic events in patients on a mechanical ventilator.
AB  - BACKGROUND: Mechanical ventilation is an important tool in the management of
      respiratory failure in the critically ill patient. Although mechanical
      ventilation can be a life-saving intervention, it is also known to carry several
      side-effects and risks. Adequate oxygenation is one of the primary goals of
      mechanical ventilation. However, while on mechanical ventilation, patients
      frequently experience hypoxic events resulting from various causes, which need to
      be properly evaluated and treated. MATERIALS AND METHODS: Data were obtained by
      prospectively reviewing all intensive care admissions during the period from
      March 2009 to March 2010 at a 651-bed urban medical center. Patients who
      developed hypoxemia (oxygen saturation <=88% and a PaO2<=60 torrs) while on
      mechanical ventilation were investigated for the cause of hypoxic event. RESULTS:
      During the study period, 955 patients required mechanical ventilation from which
      79 developed acute hypoxia. The causes of acute hypoxia in decreasing order of
      occurrences were pulmonary edema, atelectasis, pneumothorax, pneumonia, ARDS,
      endotracheal tube malfunction, airway bleeding, and pulmonary embolism.
      CONCLUSIONS: Appropriate evaluation of all hypoxic events must begin at the
      bedside. A step-by-step approach must include a thorough physical examination.
      Evaluation of the endotracheal tube can immediately reveal dislodgement,
      bleeding, and secretions. Correlation of physical examination findings with those
      on chest radiograph is essential. Each hypoxic event requires a different
      intervention depending on its etiology. Instead of simply increasing the fraction
      of oxygen in the inspired air to overcome hypoxia, a concerted effort in
      appropriate problem solving can reduce the likelihood of an incorrect diagnosis
      and management response.

PMID- 23961458
TI  - Wind disasters: A comprehensive review of current management strategies.
AB  - Wind disasters are responsible for tremendous physical destruction, injury, loss
      of life and economic damage. In this review, we discuss disaster preparedness and
      effective medical response to wind disasters. The epidemiology of disease and
      injury patterns observed in the early and late phases of wind disasters are
      reviewed. The authors highlight the importance of advance planning and adequate
      preparation as well as prompt and well-organized response to potential damage
      involving healthcare infrastructure and the associated consequences to the
      medical response system. Ways to minimize both the extent of infrastructure
      damage and its effects on the healthcare system are discussed, focusing on
      lessons learned from recent major wind disasters around the globe. Finally,
      aspects of healthcare delivery in disaster zones are reviewed. 

PMID- 23961459
TI  - Prophylaxis and treatment of venous thromboembolism in the critically ill.
AB  - Venous thromboembolism (VTE) is a frequent complication in critically ill
      patients and is associated with increased rates of morbidity and mortality. The
      use of thromboprophylaxis to reduce the risk of VTE in this patient population is
      the standard of care. This review will summarize the recommendations set forth in
      consensus guidelines for the prevention and treatment of VTE across subgroups
      within the critically ill patient population. In addition, the drug properties of
      the recommended pharmacologic agents for thromboprophylaxis will be highlighted
      including their pharmacokinetics, dosing and complications. The critical care
      practitioner may also encounter novel oral anticoagulants with increasing
      frequency. These agents will be briefly reviewed in terms of their approved and
      investigational indications and the clinical concerns related to their use will
      also be discussed. 

PMID- 23961460
TI  - Anaphylaxis due to spontaneous rupture of primary isolated splenic hydatid cyst.
AB  - Echinococcosis is a helminthic zoonosis mainly caused by Echinococcus granulosus
      and commonly encountered in endemic areas. The liver and lung are the most
      frequently involved organs. A primary isolated hydatid cyst of spleen is an
      extremely rare disease even in endemic areas. Anaphylactic reaction is a known
      complication of cystic hydatid disease, a parasitic infestation caused by the
      larval/cyst stage of E. granulosus that usually occurs after trauma or during
      interventions. To the best of our knowledge, anaphylaxis with spontaneous rupture
      of primary isolated splenic hydatidoses had not been reported previously. The
      main purpose of this report is to highlight life-threatening complications such
      as anaphylactic shock that should be considered due to primary isolated splenic
      cyst hydatid rupture in especially endemic regions. 

PMID- 23961461
TI  - Traumatic pulmonary pseudocyst.
AB  - Blunt thoracic trauma manifests in various ways, depending on the structures
      injured and type of injury. Commonly manifested as parenchymal contusion, at
      times, pseudacavitation may also been seen on the chest X ray. They are to be
      differentiated from other causes of pulmonary cavitations which are often done
      based on history. The so called pulmonary pseudo cysts usually have a benign
      course and needs only observation. 

PMID- 23961462
TI  - Polyuria following an overdose.
AB  - Case report detailing the occurrence of diabetes insipidus in a 42-year-old man
      admitted to the intensive treatment unit (ITU) following an overdose. Whilst on
      ITU, he was sedated with propofol. Cessation of treatment with propofol coincided
      with resolution of the polyuria. Animal studies suggest a theoretical mechanism
      for propofol as the causative agent, but this phenomenon is not commonly seen in
      humans. 

PMID- 23961463
TI  - Is normal saline really 'normal'?

PMID- 23961464
TI  - Intrapulmonary malposition of a chest drain.

PMID- 23961465
TI  - Considering multidrug resistant nosocomial sinusitis in intensive care unit
      patients as a cause of pyrexia.

PMID- 23961466
TI  - Critical issues in a parturient with pre-existing neurological deficits with
      severe anaemia: A clinical challenge to anaesthesiologist and intensivist!

PMID- 23961467
TI  - Height outcome of patients with congenital adrenal hyperplasia due to 21
      hydroxylase deficiency: Evidence from recent data.

PMID- 23961468
TI  - Trends in endocrine onomastics: The case of polycystic ovarian syndrome.

PMID- 23961469
TI  - South Asian women with diabetes: Psychosocial challenges and management:
      Consensus statement.
AB  - Diabetes is the ninth leading cause of death in women globally. In South Asians
      mortality in women with diabetes stands second highest. There is a marked gender
      discrimination which is faced by women across South Asia esp in access to
      services and support for diabetes, resulting in high rates of morbidity and
      mortality in women with diabetes. The most important risk factor identified for
      the diabetes epidemic is obesity along with genetic susceptibility. Lack of
      health care, social and cultural disparity, discrimination at work, disparity in
      marriage, restricted medical facilities are prevalent. Diabetes and depression
      are common in women. Increasing age, low level of education, low socioeconomic
      conditions, difficulties posed in finding partners, frequent divorce and family
      history of psychiatric illness are significant risk factors for diabetes and
      depression. Such patients usually have poor metabolic control, higher
      complication rates, increased healthcare costs, lost productivity, lower quality
      of life as well as increased risk of death. Preconception counseling should be
      incorporated in the routine diabetes clinic visit for all women of childbearing
      potential. Women with diabetes should have information and access to
      contraception. Proper family planning counseling and psychological support can
      help stop practices such as female foeticide and multiple pregnancies.
      Psychological support to patients and their families are needed to break the
      barrier. There is emerging evidence that women with diabetes are more prone to
      untoward outcomes as compared to men. Central obesity, metabolic syndrome and the
      polycystic ovary syndrome show ethnic specific differences in South Asian women.
      Optimal sexuality is an integral part of holistic health. Shortage of trained
      female health care professionals, lack of privacy in over-crowded health care
      facilities, a social taboo attached to such matters, and lack of confidence in
      patients contribute to the neglect of sexual issues in women attending diabetes
      clinics across South Asia. Guidelines for counselling in female sexual
      dysfunction, written in culturally appropriate manner for South Asia, are needed.
      Diabetes affects women more severely because of their unique biological, cultural
      and socioeconomic circumstances. Women have limited access to health care
      facilities because of illiteracy, ignorance and negative social customs.
      Transcending the gender hierarchy and inequality is a formidable challenge.
      Sensitising men, empowering women on self care and providing peer support maybe
      the answer to this challenge. It is essential for health care providers to use
      appropriate coping mechanism such as building psychological contact with the
      patient, including family and friends as part of social support and empower
      patient with complete process of managing diabetes. Increasing awareness through
      the media, seminars, posters, group discussions and education, regular monitoring
      and consulting the doctor, support group for women and facilities for aerobic
      exercises are recommended. The health care systems should consider custom
      designed prevention and control programs tailored for women based on local and
      regional attitudes on health care, cultural beliefs, and available social support
      systems. Policies that empower adolescent girls and young women to take control
      of their metabolic management must be encouraged. Provision of gender specific
      diabetes education with a holistic life-cycle approach is recommended. 

PMID- 23961470
TI  - Acromegaly: Beyond surgery.
AB  - Acromegaly is characterized by chronic, excess secretion of growth hormone (GH)
      from a pituitary adenoma, and elevated hepatic insulin-like growth factor 1 (IGF
      1) levels. Significant progress has been made in the development of medical
      therapies to achieve biochemical and symptomatic control in acromegaly. In this
      review we discuss the three currently available medical therapies, which include
      somatostatin analogs, dopamine agonists and pegvisomant. We describe a step-wise
      approach in which a somatostatin analog is followed by the addition of a dopamine
      agonist, and then if required the addition of or replacement by pegvisomant. New
      somatostatin agonists such as pasireotide, and the introduction of new orally
      acting somatostatin agonists, should increase the therapeutic choices available
      in the near future. 

PMID- 23961471
TI  - Fetal endocrinology.
AB  - Successful outcome of pregnancy depends upon genetic, cellular, and hormonal
      interactions, which lead to implantation, placentation, embryonic, and fetal
      development, parturition and fetal adaptation to extrauterine life. The fetal
      endocrine system commences development early in gestation and plays a modulating
      role on the various physiological organ systems and prepares the fetus for life
      after birth. Our current article provides an overview of the current knowledge of
      several aspects of this vast field of fetal endocrinology and the role of
      endocrine system on transition to extrauterine life. We also provide an insight
      into fetal endocrine adaptations pertinent to various clinically important
      situations like placental insufficiency and maternal malnutrition. 

PMID- 23961472
TI  - Impact of alcohol use on thyroid function.
AB  - Alcohol is one of the commonest illicit psychoactive substances consumed globally
      and is the world's third largest risk factor for disease and disability. It has
      been reported to have multiple effects on the hypothalamo-pituitary-thyroid axis
      and the functioning of the thyroid gland. It has been reported to cause direct
      suppression of thyroid function by cellular toxicity, and indirect suppression by
      blunting thyrotropin-releasing hormone response. It causes a decrease of
      peripheral thyroid hormones during chronic use and in withdrawal. Alcohol use may
      also confer some protective effect against thyroid nodularity, goiter, and
      thyroid cancer. This article presents a review of the clinically relevant effects
      of alcohol on the functioning of the thyroid gland and also discusses the effect
      of medication used in treatment of alcohol dependence on thyroid function. 

PMID- 23961473
TI  - Renal glucose handling in diabetes and sodium glucose cotransporter 2 inhibition.
AB  - The kidneys play a major role in glucose homeostasis through its utilization,
      gluconeogenesis, and reabsorption via sodium glucose cotransporters (SGLTs). The
      defective renal glucose handling from upregulation of SGLTs, mainly the SGLT2,
      plays a fundamental role in the pathogenesis of type 2 diabetes mellitus. Genetic
      mutations in a SGLT2 isoform that results in benign renal glycosuria, as well as
      clinical studies with SGLT2 inhibitors in type 2 diabetes support the potential
      of this approach. These studies indicate that inducing glycosuria by suppressing
      SGLT2 can reduce plasma glucose and A1c levels, as well as decrease weight,
      resulting in improved beta-cell function and enhanced insulin sensitivity in
      liver and muscle. Because the mechanism of SGLT2 inhibition is independent of
      insulin secretion and sensitivity, these agents can be combined with other
      antidiabetic agents, including exogenous insulin. This class represents a novel
      therapeutic approach with potential for the treatment of both type 2 and type 1
      diabetes. 

PMID- 23961474
TI  - Barriers and solutions to diabetes management: An Indian perspective.
AB  - India, with one of the largest and most diverse populations of people living with
      diabetes, experiences significant barriers in successful diabetes care.
      Limitations in appropriate and timely use of insulin impede the achievement of
      good glycemic control. The current article aims to identify solutions to barriers
      in the effective use of insulin therapy viz. its efficacy and safety, impact on
      convenience and life-style and lack of awareness and education. Therapeutic
      modalities, which avoid placing an undue burden on patients' life-style, must be
      built. These should incorporate patient-centric paradigms of diabetes care, team
      based approach for life-style modification and monitoring of patients' adherence
      to therapy. To address the issues in efficacy and safety, long-acting, flat
      profile basal insulin, which mimics physiological insulin and show fewer
      hypoglycemic events is needed. In addition, therapy must be linked to monitoring
      of blood glucose to enable effective use of insulin therapy. In conjunction, wide
      ranging efforts must be made to remove negative perception of insulin therapy in
      the community. Patient- and physician - targeted programs to enhance awareness in
      various aspects of diabetes care must be initiated across all levels of health
      care ensuring uniformity of information. To successfully address the challenges
      in facing diabetes care, partnerships between various stakeholders in the care
      process must be explored. 

PMID- 23961475
TI  - Extraskeletal effects and manifestations of Vitamin D deficiency.
AB  - The actions of vitamin D are not confined to bone. Vitamin D receptors are
      present in nearly all the nuclei and its actions are manifold. Populations
      deficient in vitamin D are at higher risk of developing autoimmune diseases,
      diabetes, cancer, infections, allergies and other chronic illnesses. 

PMID- 23961476
TI  - Glycemic variability: Clinical implications.
AB  - Glycemic control and its benefits in preventing microvascular diabetic
      complications are convincingly proved by various prospective trials. Diabetes
      control and complications trial (DCCT) had reported variable glycated hemoglobin
      (HbA1C) as a cause of increased microvascular complications in conventional
      glycemic control group versus intensive one. However, in spite of several
      indirect evidences, its link with cardiovascular events or macrovascular
      complications is still not proved. Glycemic variability (GV) is one more tool to
      explain relation between hyperglycemia and increased cardiovascular risk in
      diabetic patients. In fact GV along with fasting blood sugar, postprandial blood
      sugar, HbA1C, and quality of life has been proposed to form glycemic pentad,
      which needs to be considered in diabetes management. Postprandial spikes in blood
      glucose as well as hypoglycemic events, both are blamed for increased
      cardiovascular events in Type 2 diabetics. GV includes both these events and
      hence minimizing GV can prevent future cardiovascular events. Modern diabetes
      management modalities including improved sulfonylureas, glucagon like peptide-1
      (GLP-1)-based therapy, newer basal insulins, and modern insulin pumps address the
      issue of GV effectively. This article highlights mechanism, clinical
      implications, and measures to control GV in clinical practice. 

PMID- 23961477
TI  - Renal phosphate handling: Physiology.
AB  - Phosphorus is a common anion. It plays an important role in energy generation.
      Renal phosphate handling is regulated by three organs parathyroid, kidney and
      bone through feedback loops. These counter regulatory loops also regulate
      intestinal absorption and thus maintain serum phosphorus concentration in
      physiologic range. The parathyroid hormone, vitamin D, Fibrogenic growth factor
      23 (FGF23) and klotho coreceptor are the key regulators of phosphorus balance in
      body. 

PMID- 23961478
TI  - Journey in guidelines for lipid management: From adult treatment panel (ATP)-I to
      ATP-III and what to expect in ATP-IV.
AB  - Adult Treatment Panel (ATP), an expert panel to supervise cholesterol management
      was set up under the aegis of National Cholesterol Education Program (NCEP) in
      1985. Since then NCEP-ATP has been revising and framing guidelines to enable
      clinician to deliver better treatment to cardiovascular patients and to educate
      general people. As a result, considerable reduction in cardiovascular related
      deaths has been observed in recent times. All three ATP guidelines viz. ATP-I,
      ATP-II and ATP-III have targeted low density lipoprotein as their primary goal.
      The ATP-III guideline was updated in the light of evidences from 5-major clinical
      trials and was released in 2004. It added therapeutic lifestyle changes, concept
      of risk equivalents, Framingham CHD-risk score non-high density lipoprotein
      cholesterol (non-HDL-C) as secondary target and gave strong emphasis on metabolic
      risk factors. The earlier treat-to-target paradigm faced fierce criticism from
      clinicians across the globe because of insufficient proof of safety and benefits
      of treating patients with respect to an individual's low density lipoprotein
      (LDL) level. Further, demonstration of non-HDL-C and total cholesterol/HDL-C
      ratio as strong predictors of overall cardiovascular risk foresees new
      guidelines. A tailored-treatment approach was suggested instead of LDL-C target
      based treatment approach which was soundly based on direct clinical trials
      evidences and proposes treatment based on individual's overall 5- to 10-year
      cardiovascular risk irrespective of LDL-C level, leading to lower number of
      people on high dose/s of statins. Recent report of the Cholesterol Treatment
      Trialist's Collaborators meta-analysis strongly supported primary prevention of
      LDL with statins in low risk individuals and showed that its benefits completely
      outweighed its known hazards. Markers other than LDL-C like apolipoprotein B, non
      HDL-C and total cholesterol/HDL-C ratio would take precedence in the risk
      assessment and strong emphasis would be given on tailored-treatment approach in
      the upcoming ATP-IV guideline. 

PMID- 23961481
TI  - Community based diabetes risk assessment in Ogun state, Nigeria (World Diabetes
      Foundation project 08-321).
AB  - OBJECTIVE: The study assessed the risk of developing type 2 diabetes Mellitus in
      Ogun State, Nigeria. MATERIALS AND METHODS: Finnish Medical Association diabetes
      risk score was administered across 25 communities facilitated by non-communicable
      disease clinics established under a World Diabetes Foundation project. Subjects
      in the high risk group had blood glucose estimated. RESULTS: 58,567 respondents
      included 34,990 (59.6%) females and 23,667 (40.3%) males. Majority (61.2%) were
      between 25 years and 54 years. Considering waist circumference, 34,990 (38.1%)
      females and 23,667 (5.3%) males had values above 88 cm and 102 cm respectively.
      Overall, 11,266 (19.2%) were obese and 28.9% overweight using body mass index
      (BMI). More females had elevated BMI than males. Mean systolic blood pressure
      (SBP) and diastolic blood pressure (DBP) of all subjects were 129.54 mm Hg +/-
      23.5 mm Hg and 76.21 mm Hg +/- 15.5 mm Hg respectively. Prevalence of
      hypertension (Joint National Committee VII classification) was 27.7%. More
      subjects had normal DBP than SBP (68.2% vs. 42.5% P < 0.05). Mean fasting blood
      glucose (FBG) of all subjects was 5.5 mmol/L +/- 0.67 mmol/L. Using a casual
      blood glucose >11.1 mmol/L and/or FBG >7 mmol/L, the total yield of subjects
      adjudged as having diabetes was 2,956 (5.05%). Mean total risk score was 5.60 +/-
      3.90; this was significantly higher in females (6.34 +/- 4.16 vs. 4.24 +/- 3.71,
      P < 0.05). A total of 2,956 (5.05%) had high risk of developing DM within 10
      years. CONCLUSION: The risk of developing DM is high in the community studied
      with females having a higher risk score. There is urgent need to implement
      diabetes prevention strategies.

PMID- 23961479
TI  - Safety of statins.
AB  - Statins are an established class of drugs with proven efficacy in cardiovascular
      risk reduction. The concern over statin safety was first raised with the
      revelation of myopathy and rhabdomyolysis with the use of now withdrawn
      cerivastatin. Enhanced understanding of the mechanisms behind adverse effects of
      statins including an insight into the pharmacokinetic properties have minimised
      fear of statin use among clinicians. Studies reveal that occurrence of myopathy
      and rhabdomyolysis are rare 1/100000 patient-years. The risk of
      myopathy/rhabdomyolysis varies between statins due to varying pharmacokinetic
      profiles. This explains the differing abilities of statins to adverse effects and
      drug interaction potentials that precipitate adverse effects. Higher dose of
      rosuvastatin (80 mg/day) was associated with proteinuria and hematuria while
      lower doses were devoid of such effects. Awareness of drugs interacting with
      statins and knowledge of certain combinations such as statin and fibrates
      together with monitoring of altered creatine kinase activity may greatly minimise
      associated adverse effects. Statins also asymptomatically raise levels of hepatic
      transaminases but are not correlated with hepatotoxicity. Statins are safe and
      well tolerated including more recent potent statins such as, rosuvastatin. The
      benefits of intensive statin use in cardiovascular risk reduction greatly
      outweigh risks. The present review discusses underlying causes of statin
      associated adverse effects including management in high risk groups. 

PMID- 23961480
TI  - Prevalence of hypothyroidism in adults: An epidemiological study in eight cities
      of India.
AB  - BACKGROUND: Hypothyroidism is believed to be a common health issue in India, as
      it is worldwide. However, there is a paucity of data on the prevalence of
      hypothyroidism in adult population of India. MATERIALS AND METHODS: A cross
      sectional, multi-centre, epidemiological study was conducted in eight major
      cities (Bangalore, Chennai, Delhi, Goa, Mumbai, Hyderabad, Ahmedabad and Kolkata)
      of India to study the prevalence of hypothyroidism among adult population.
      Thyroid abnormalities were diagnosed on the basis of laboratory results (serum
      FT3, FT4 and Thyroid Stimulating Hormone [TSH]). Patients with history of
      hypothyroidism and receiving levothyroxine therapy or those with serum free T4
      <0.89 ng/dl and TSH >5.50 MUU/ml, were categorized as hypothyroid. The prevalence
      of self reported and undetected hypothyroidism, and anti-thyroid peroxidase (anti
      TPO) antibody positivity was assessed. RESULTS: A total of 5376 adult male or non
      pregnant female participants >=18 years of age were enrolled, of which 5360 (mean
      age: 46 +/- 14.68 years; 53.70% females) were evaluated. The overall prevalence
      of hypothyroidism was 10.95% (n = 587, 95% CI, 10.11-11.78) of which 7.48% (n =
      401) patients self reported the condition, whereas 3.47% (n = 186) were
      previously undetected. Inland cities showed a higher prevalence of hypothyroidism
      as compared to coastal cities. A significantly higher (P < 0.05) proportion of
      females vs. males (15.86% vs 5.02%) and older vs. younger (13.11% vs 7.53%),
      adults were diagnosed with hypothyroidism. Additionally, 8.02% (n = 430) patients
      were diagnosed to have subclinical hypothyroidism (normal serum free T4 and TSH
      >5.50 MUIU/ml). Anti - TPO antibodies suggesting autoimmunity were detected in
      21.85% (n = 1171) patients. CONCLUSION: The prevalence of hypothyroidism was
      high, affecting approximately one in 10 adults in the study population. Female
      gender and older age were found to have significant association with
      hypothyroidism. Subclinical hypothyroidism and anti-TPO antibody positivity were
      the other common observations.

PMID- 23961482
TI  - Skin, a mirror reflecting diabetes mellitus: A longitudinal study in a tertiary
      care hospital in Gujarat.
AB  - CONTEXT: Diabetes mellitus (DM) is the most common of the endocrine disorders.
      Mucocutaneous manifestations of diabetes mellitus are many and vary from trivial
      to life-threatening. Sometimes, mucocutaneous disorders may herald the onset of
      diabetes. AIMS: To study the pattern of mucocutaneous manifestations in diabetics
      and role of it in diagnosing diabetes mellitus and its complications. SETTINGS
      AND DESIGN: It was a longitudinal observational study of patients having diabetes
      with skin complaints attending skin outdoor department or admitted in wards for
      any reason in a tertiary care hospital. MATERIALS AND METHODS: Total 300 patients
      were included in the study. Detailed history, clinical examination, and relevant
      investigations were done to diagnose the mucocutaneous disorders, diabetes, and
      diabetic complications. STATISTICAL ANALYSIS USED: The data was analyzed by using
      Epi info software. RESULTS: Demographic profile shown majority of cases (78.66%)
      in more than 40 years of age with almost equal male and female preponderance.
      Mucocutaneous manifestations as presenting feature of diabetes were observed in
      21.67% cases. Infections were most common in 119 (39.66%) cases, followed by
      acanthosis nigricans in 46 (15.33%) cases. Various associated complications like
      hypertension, retinopathy, hyperlipidemia, coronary artery disease, neuropathy,
      nephropathy, and diabetic ketoacidosis were observed in 160 (53.3%). CONCLUSIONS:
      Skin is the mirror, which reflects internal diseases; this aptly applies to skin
      and diabetes mellitus. Through awareness about cutaneous manifestations of DM,
      dermatologist can not only take credit for detecting DM but also facilitate early
      diagnosis of systemic complications of DM. This is immensely beneficial to
      patients in long run.

PMID- 23961483
TI  - Clinicopathological characteristics and metabolic profiles of non-alcoholic fatty
      liver disease in Indian patients with normal body mass index: Do they differ from
      obese or overweight non-alcoholic fatty liver disease?
AB  - BACKGROUND: Obesity is an important risk factor for non-alcoholic fatty liver
      disease (NAFLD); however, NAFLD does occur in lean subjects. This study was aimed
      to evaluate the magnitude, clinical, pathological, and metabolic profiles of
      NAFLD in normal body mass index (BMI) subjects (defined as lean NAFLD) in
      comparison to overweight or obese NAFLD and lean healthy control. MATERIALS AND
      METHODS: 336 subjects (205 consecutive NAFLD, and 131 healthy controls) were
      studied. RESULTS: Among 205 NAFLD patients, 27 (13.2%) were lean, while 141
      (68.8%) and 37 (18%) patients were obese and overweight, respectively. The lean
      NAFLD compared to obese NAFLD had significantly lesser degree of fasting
      hyperinsulinemia (P < 0.001), homeostasis model assessment insulin resistance
      (HOMA-IR, P < 0.001), and lower prevalence of diabetes mellitus (P = 0.01) and
      metabolic syndrome (P < 0.001). The profiles of serum lipids were similar between
      all 3 BMI categories, and 89% of lean NAFLD were dyslipidemic. Compared to obese
      subjects, patients with lean NAFLD had less hepatic necro-inflammation (P = 0.05)
      and fibrosis (P < 0.001). However, the proportion of steatohepatitis and advanced
      fibrosis were similar between all BMI categories. The profiles of overweight
      NAFLD were similar to those of lean NAFLD, except for higher HOMA-IR, uric acids
      and male gender in overweight group. Despite being lean, the mean BMI of lean
      NAFLD were still higher than unselected lean healthy controls (P = 0.02).
      CONCLUSIONS: Lean NAFLD patients have less severe disease, minor, or no insulin
      resistance, but are frequently dyslipidemic and have BMI higher than lean healthy
      control.

PMID- 23961484
TI  - Anthropometric characteristics and dietary pattern of women with polycystic ovary
      syndrome.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder
      among women of reproductive age. PCOS is considered to be not only a reproductive
      endocrinopathy, but also a metabolic disorder. The objective of the present study
      was to characterize the anthropometric and dietary profile of women with PCOS and
      to compare it with that of healthy age-matched women. DESIGN: In this case
      control study, 65 women with PCOS served as cases. The control group consisted of
      65 age-matched healthy women. For each participant, demographic, anthropometric
      and dietary intake data were gathered and compared between the two groups.
      RESULTS: There was no significant difference between the mean of the body mass
      index of the two groups, but the mean of waist circumference was significantly
      higher in the PCOS group, than the control group (P = 0.016). Compared to the
      normal weight PCOS patients, a significantly higher percentage of overweight
      patients had hirsutism (P = 0.009). In dietary analysis, women with PCOS consumed
      more calories and more fat than healthy women (P = 0.001 and P = 0.019,
      respectively). CONCLUSION: It is concluded that in PCOS patients, android obesity
      is a common feature and this abdominal adiposity may be related to the syndrome's
      complications. PCOS symptoms were more severe in overweight patients than the
      normal weight. Regarding the dietary pattern, it was indicated that patients with
      PCOS consume more calories and more fat in their diets and this might have been
      correlated to their disease.

PMID- 23961485
TI  - Prevalence of gestational diabetes mellitus and its outcome in western Rajasthan.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disorder defined
      as glucose intolerance with the onset or first recognition during pregnancy.
      Women with GDM are at increased risk for adverse obstetric and perinatal outcome.
      Hence, it is imperative that an early detection and management of the disease is
      done to ensure better maternal and fetal outcomes. AIMS: This study was done to
      evaluate the prevalence of gestational diabetes using diabetes in pregnancy Study
      Group India (DIPSI) criteria and further assess its feto-maternal outcome in
      western Rajasthan. MATERIALS AND METHODS: This study was carried out in 500
      patients between 24 and 28 weeks of gestation, attending the antenatal outdoor.
      These patients were given 75 g oral glucose irrespective of the meals and their
      plasma glucose was estimated at 2 h. Patients with plasma glucose values ?140
      mg/dl were labeled as GDM and the rest as the control or the non-GDM group. All
      GDM patients were followed up and treated with diet and/or insulin therapy till
      delivery to know maternal and fetal outcomes. RESULTS: The prevalence of GDM in
      this study was 6.6%. Maternal and fetal complications in the GDM group were much
      higher than in the non-GDM group. Hypertension, vaginal candidiasis, and abruptio
      placentae were the common maternal complications, while macrosomia and
      stillbirths occurred in the fetuses. CONCLUSION: GDM as a disease entity
      adversely affects maternal and fetal outcomes. This also builds a strong case for
      following DIPSI guidelines in diagnosis and management of GDM.

PMID- 23961486
TI  - Proportion of depression and its determinants among type 2 diabetes mellitus
      patients in various tertiary care hospitals in Mangalore city of South India.
AB  - BACKGROUND: Depression is found to be common among patients with diabetes and it
      is associated with poor outcomes in disease control. This study was carried out
      to find out the proportion and determinants associated with depression among
      patients with established type 2 diabetes mellitus (T2DM) in various tertiary
      care hospitals in Mangalore city of south India. MATERIALS AND METHODS: This
      study was conducted in one government and three private tertiary care hospitals
      in Mangalore in December 2010. All consenting patients with confirmed diagnosis
      of T2DM were interviewed and screened for depression by administering the 9-item
      PRIME-MD Patient Health Questionnaire (PHQ-9). RESULTS: Of the 230 T2DM patients,
      119 (51.7%) were males. The mean age of all participants was 53.61 +/- 10.7
      years. The median duration of T2DM was found to be 12.1 +/- 7.35 years. Among the
      participants, 71 (30.9%) met the criteria for moderate depression, 33 (14.3%) for
      severe depression, and the remaining 126 (54.8%) had no clinically significant
      depression. Only 26 (11.3%) patients were already aware that they were depressed,
      of whom just 3 had taken medical consultation. Among the risk factors, depression
      was found to be significantly associated with older age, female gender, low
      socioeconomic status, unskilled and retired employment status, having
      complications due to T2DM or comorbidities like hypertension and coronary artery
      disease, being overweight and being on insulin syringe injections. CONCLUSION:
      This study found a high proportion of depression among patients with T2DM.
      Therefore the care of individuals with diabetes mellitus (DM) should include the
      screening and possible treatment of depression in order to achieve and sustain
      treatment goals.

PMID- 23961487
TI  - Effect of low glycemic load diet with and without wheat bran on glucose control
      in gestational diabetes mellitus: A randomized trial.
AB  - BACKGROUND: A low-glycemic index diet is effective in blood glucose control of
      diabetic subjects, reduces insulin requirement in women with gestation diabetes
      mellitus (GDM) and improves pregnancy outcomes when used from beginning of the
      second trimester. However there are limited reports to examine the effect of low
      glycemic load (LGL) diet and fiber on blood glucose control and insulin
      requirement of women with GDM. Therefore, the aim of this study was to examine
      the effect of low glycemic load diet with and without fiber on reducing the
      number of women with GDM requiring insulin. MATERIALS AND METHODS: All GDM women
      (n = 31) were randomly allocated to consume either a LGL diet with Fiber or LGL
      diet. RESULTS: We found that 7 (38.9%) of 18 women with GDM in Fiber group and 10
      (76.9%) in "Without Fiber" group required insulin treatment. CONCLUSION: The LGL
      diet with added fiber for women with GDM dramatically reduced the number needing
      for insulin treatment.

PMID- 23961488
TI  - The 1 MUg cosyntropin test in normal individuals: A reappraisal.
AB  - BACKGROUND: The 1MUg cosyntropin test has some advantages over the 250MUg test as
      a test of adrenal function. One of the concerns regarding the 1 MUg test includes
      stability of the cosyntropin when reconstituted and stored. Classically the 5(th)
      percentile responses to cosyntropin in normal individuals have been used to
      define a normal response. Recent studies have shown that these normative values
      should be determined for individual assays. MATERIALS AND METHODS: We performed a
      1MUg cosyntropin test using reconstituted and refrigerated (4-8( degrees ) C)
      cosyntropin in saline solution in 49 non pregnant adults who were apparently
      healthy and had no exposure to exogenous glucocorticoids. The cosyntropin
      solution was stored for up to 60 days following reconstitution. We analysed the
      data for any association between duration of cosyntropin solution storage and the
      cortisol responses to cosyntropin administration. RESULTS: The mean +/- SD
      cortisol level at baseline, 30 and 60 min were-12.19 +/- 3 MUg/dl, 20.72 +/- 2.63
      MUg/dl, 16.86 +/- 3.33 MUg/dl. The 5(th) percentile cortisol response at 30 min
      was 16.5 MUg/dl (16.33 MUg/dl rounded off). The correlation coefficients between
      number of days of cosyntropin solution storage and the cortisol responses at 30
      and 60 min were (Spear mans rho = 0.06,-0.24 respectively) (P = 0.69 and 0.41).
      There were no differences in cortisol values whether the storage was for less
      than 30 days or more than 30 days (mean difference 0.25 MUg/dl P = 0.44).
      CONCLUSION: The 5(th) percentile normative values determined for our assay is
      lower than what is currently being used clinically and in research publications.
      Prolonged refrigerated storage of cosyntropin solution does not affect the
      validity of the 1 MUg cosyntropin test.

PMID- 23961490
TI  - Knowledge of diabetes mellitus in tuberculosis amongst healthcare workers in
      Nigeria.
AB  - BACKGROUND: There is a World Diabetes Foundation funded research on detection of
      diabetes mellitus (DM) in tuberculosis (TB) which is currently being carried out
      in 56 TB centers in Lagos State Nigeria and against this background, we decided
      to evaluate the knowledge of DM and (TB) amongst the health workers from these
      facilities. MATERIALS AND METHODS: We employed the use of self-administered
      questionnaires comprising questions to determine participant's knowledge on risk
      factors, clinical presentation and complications of DM, diagnosis, management of
      DM, and presentation and management of TB. We documented and also compared
      responses that differed in a statistically significant manner amongst the various
      cadres of health worker and the three tiers of healthcare facilities. RESULTS: A
      total of 263 health care workers responded, out of which medical doctors
      constituted 72 (27.4%) while nurses and other categories of health care workers
      constituted 191 (72.6%). All the respondents knew that TB is a communicable
      disease and a large majority- 86% knew that DM is a chronic disorder that as of
      now has no cure. One hundred and eighty one (71%) respondents gave a correct
      response of a fasting plasma glucose level of 9mmol/L, which is in the range for
      diagnosis of DM. About a third-90-of the health workers, however, stated that DM
      may be diagnosed solely on clinical symptoms of DM. However, 104 (46%) of the
      Study participants stated that urine may be employed for objectively diagnosing
      DM. All respondents had hitherto not had patients with TB who had been routinely
      screened for DM. There was insufficient knowledge on the non-pharmacological
      management with over half of the respondents, irrespective ofstatus, maintained
      that all persons diagnosed with DM should be made to lose weight and carbohydrate
      should make up less than 30% of the component of their meals. CONCLUSION: There
      remains largely inadequate knowledge on diagnosing and non-pharmacological
      management of DM among the health workers in our TB facilities.

PMID- 23961489
TI  - Clinical, biochemical, and radiological manifestations of vitamin D deficiency in
      newborns presented with hypocalcemia.
AB  - INTRODUCTION: The Clinical and radiological manifestations of newborns with
      severe VDD have not been studied well. MATERIALS AND METHODS: We studied the
      clinical, biochemical, and radiological manifestations of 10 full-term (FT)
      newborns (6: M, 4: F) infant presented to with symptomatic hypocalcemia (seizure)
      secondary to vitamin D deficiency (VDD) during the first 10 days of life are
      described. All were exclusively breastfed since birth. All their mothers have low
      25 hydroxy vitamin D (25OHD) level <10 ng/mL and were not taking vitamin
      supplements during pregnancy. RESULTS: FT newborns with hypocalcemia secondary to
      VDD presented with generalized convulsions (10/10) and craniotabes (8/10), but
      none had rachitic chest rosaries or joint broadening. Cranial ultrasonographic
      evaluation was normal. Serum 25OHD concentrations were low in these newborns
      (13.2 +/- 3.8 ng/mL) and their mothers (8.1 +/- 1.5 ng/mL). A total of 60% of
      them had increased parathormone (PTH) concentrations (>60 ng/mL) and 60% had
      decreased magnesium (Mg) concentrations (<0.7 mmol/L). Their alkaline phosphatase
      (ALP) concentrations were significantly higher than normal newborns. All other
      laboratory results (liver function tests, urea and electrolytes, C reactive
      protein, lumbar puncture, blood culture, and lactate) were normal. In all
      patients, seizures ceased within 2 days of starting treatment with alphacalcidol
      and calcium. Radiological manifestations included metaphyseal band of relative
      lucency (osteopenia), just under the line of provisional calcification, within
      distal radius (7/10), femur (4/10), and tibia (3/10), mild cupping and haziness
      of distal radius (2/10). DISCUSSION: Newborns with VDD had significantly lower
      serum calcium, ALP and PTH and higher phosphate concentrations, compared to older
      infants with VDD rickets. In newborns with VDD, serum calcium levels were
      correlated significantly with 25OHD (r = 0.597, P < 0.001), Mg concentrations (r
      = 0.436, P < 0.001) and negatively with ALP concentrations (r = -0.451, P <
      0.001). Serum PTH concentrations were correlated significantly with serum Mg (r =
      0.78, P < 0.0001) but not with serum calcium (r = -0.103, P = 0.3) or 25OHD (r = 
      0.03, P = 0.7) concentrations. CONCLUSION: The clinical, biochemical, and
      radiological manifestations of VDD in newborns indicate that they are less
      adapted to VDD compared to older infants. VD supplementation for mothers and
      newborns should be considered to avoid short-term complications of VDD in the
      neonatal period and on the growing infants especially in countries with high
      prevalence of VDD.

PMID- 23961491
TI  - Efficacy and safety of pioglitazone in type 2 diabetes in the Indian patients:
      Results of an observational study.
AB  - OBJECTIVE: This study was undertaken to assess the efficacy and safetyof
      pioglitazone in combination with other oral antidiabetics (OADs) in Indian
      patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This was an
      openlabel, prospective, no-randomized, single-center observational study
      conducted at a single center in India. A total of 958 adult patients with T2DM on
      OADs, with uncontrolled fasting (FBG) or postprandial blood glucose (PPG), were
      enrolled. Pioglitazone (7.5/15/30 mg) was added to existing therapy as a
      combination treatment with other OAD. Body weight (BW), body mass index (BMI),
      FBG and postprandial plasma glucose (PPPG) and glycosylated hemoglobin (HbA1c)
      were measured at the beginning (week 0) and at every follow-up treatment visit,
      i.e., 6 months (week 24), 1 year (week 48) and 2 years (week 96). Changes from
      baseline to each visit were analyzed using the Wilcoxon test. All patients also
      went through a urinalysis at baseline, and after 6 months, 1 year and 2 years of
      treatment, to assess for any abnormalities in the urine (pH, pus or protein),
      suggestive of bladder abnormalities. RESULTS: The combined analysis was carried
      out on 958 completed patients in this study who were treated with pioglitazone
      7.5 mg, 15 mg and 30 mg tablet and other OADs. The difference in mean value of
      FBG showed a highly significant decrease (P < 0.0001) from baseline to end of
      treatment, i.e., from 167.0, (59.16) 172.6 (58.51) and 171.0 (39.47) to 140.2,
      (26.46) 143.8 (22.04) and 138.5 (27.82) mg/dL. Similarly, PPG showed a
      significant (P < 0.0001, 0.002 and 0.008) decrease from baseline to end of the
      treatment, i.e., from 256.0, (61.79) 222.9 (67.88) and 223.6 (69.11) to 195.9,
      (46.92) 204.0 (48.03) and 187.6 (53.36) mg/dL, and there was a highly significant
      (P < 0.0001) decrease in HbA1c levels, i.e., from 8.46, 8.34 and 8.42% to 7.781,
      7.78 and 7.73%, respectively. However, gain in mean BW was also observed from
      baseline to end of the treatment, i.e., from 69.90, (9.44) 68.29 (8.62) and 67.64
      (7.75) kg to 71.69, (8.35) 70.08 (7.96) and 69.70 (7.99) kg, respectively, and
      BMI increased from 26.74 (14.18-53.04) kg/m(2) at baseline to 27.45 (12.87-53.73)
      kg/m(2) at the end of the treatment, respectively (P < 0.0001). No significant
      changes were found in urine in patients even after 2 years of treatment with
      pioglitazone. There was little variation in pH or presence of pus and proteins in
      the urine, indicating no increased risk of bladder-related abnormalities across
      all treated age groups even after 2 years of treatment with pioglitazone.
      CONCLUSION: Pioglitazone in combination with other OADs in Indian patients was an
      effective treatment protocol in glycemic control, reduction in FBG, PPPG and
      HbA1c and also helps in controlling weight gain in patients with T2DM. In this
      patient population, there was no increased risk of bladder-related abnormalities.
      Pioglitazone was therefore found to be a safe and efficacious addition to
      treatment in patients with poorly controlled diabetes.

PMID- 23961492
TI  - Carotid intima media thickness in type 2 diabetes mellitus with ischemic stroke.
AB  - BACKGROUND: Diabetes mellitus is associated with high cardiovascular risk.
      Carotid intima media thickness (CIMT) is used commonly as a noninvasive test for
      the assessment of degree of atherosclerosis. The objective of this study was to
      find out the cut-off point for CIMT for ischemic stroke in patients with type 2
      diabetes mellitus (T2DM) and to correlate CIMT with various parameters like
      smoking, hypertension, lipid profile and duration of T2DM. MATERIALS AND METHODS:
      A total of 80 subjects in the age group of 30-75 years (M:F = 57:23) were
      selected and divided into three groups, i.e. diabetes with ischemic stroke,
      diabetes and healthy subjects. All the participants were subjected to B-mode
      ultrasonography of both common carotid arteries to determine CIMT, along with
      history taking, physical examination and routine laboratory investigations
      including included fasting and 2-hour postprandial blood sugar, blood urea, serum
      creatinine, lipid profile, glycated hemoglobin, and microalbuminuria. RESULTS:
      Patients with T2DM with or without ischemic stroke were found to have
      significantly higher prevalence of increased CIMT and a value greater than 0.8 mm
      was found to be associated with the occurrence of stroke. The mean carotid IMT of
      the group as a whole was 0.840 +/- 0.2 mm. The mean carotid IMT was not
      significantly different between T2DM patients with or without ischemic stroke
      (1.06 +/- 0.2 vs. 0.97 +/- 0.26 mm, P = 0.08). However, the mean CIMT was
      significantly higher in diabetic subjects compared to healthy subjects (1.01 +/-
      0.28 mm vs. 0.73 +/- 0.08, P = 0.006). Other parameters like higher age, smoking,
      hypertension, hyperlipidemia, low HDL cholesterol, the glycemic parameters and
      the duration of diabetes were independently and significantly related to CIMT.
      CONCLUSION: A high CIMT is a surrogate and reliable marker of higher risk of
      ischemic stroke amongst type 2 diabetic patients. Our study demonstrates the
      utility of carotid IMT as a simple non-invasive screening test for the assessment
      of atherosclerosis risk/prognosis in type 2 diabetics.

PMID- 23961493
TI  - Prevalence of metabolic syndrome among newly diagnosed hypertensive patients in
      the hills of Himachal Pradesh, India.
AB  - To study the prevalence of metabolic syndrome (MS) among newly diagnosed
      hypertensive patients in a tertiary care hospital in the northern hilly state of
      Himachal Pradesh, India, located in western Himalayas at a moderate altitude of
      2200 m above mean sea level. One hundred and eighteen newly diagnosed
      hypertensive patients above the age of 20 years were studied in a hospital-based
      cross-sectional study. MS prevalence was estimated by International Diabetes
      Federation (IDF) criteria and modified National Cholesterol Education Program
      Adult Treatment Panel III (NCEP-ATP III) criteria. Student's t-test was used to
      compare the mean of the continuous variables. Chi-square test was used to compare
      discrete variables. The prevalence of MS in hypertensive patients was 68.6%
      (modified NCEP-ATP III) and 63.6% (IDF criteria). The most common phenotype of MS
      with the component of hypertension was the coexistence of waist circumference
      (90.1%), low high-density lipoprotein (HDL; 70.4%), and high triglycerides
      (67.9%) as per the modified NCEP-ATP III criteria, and low HDL (76.2%) and high
      triglycerides (66.4%) as per the IDF criteria. Fasting blood glucose (33.2% as
      per the modified NCEP-ATP III criteria and 32.6% as per the IDF criteria) was the
      least significant factor having an association with MS. The prevalence of MS
      among hypertensive patients was high and indicates the need for metabolic
      screening in all hypertensive patients at the first diagnosis. 

PMID- 23961494
TI  - Correlations between anthropometry and lipid profile in type 2 diabetics.
AB  - Over a period of time, anthropometric parameters have evolved into reliable
      indicators for predicting the incidence of diabetes mellitus. A number of studies
      have shown correlations between anthropometry and lipid profiles in healthy
      volunteers. This study examined correlations between anthropometry and lipid
      profile in type 2 diabetics. The limited observations made in this study reveal
      that anthropometric parameters are not ideal for predicting lipid profile
      abnormalities in type 2 diabetics. 

PMID- 23961495
TI  - Severe gynecomastia due to anti androgens intake: A case report and literature
      review.
AB  - Gynecomastia is the most bothersome side effect in men taking antiandrogens. It
      is exceptionally severe and distressing physically and mentally as in the
      reported case. A man, aged 63, with a history of a well-treated
      macroprolactinoma, was referred in 2004 for gynecomastia that appeared after
      treatment by microsurgery, radiotherapy and flutamide for a lesion suspected to
      be prostate cancer. Clinical examination was normal except for huge enlargement
      of the breasts. Mammography and breasts MRI did not show any tumor. There was not
      any metastasis of the supposed prostate cancer and prostatic acid phosphates were
      within normal ranges. Hormonal exploration showed subclinical hypogonadism
      [testosterone: 7.4 ng/ml (n: 3-9), FSH: 14.9 mu/ml (n: 0.7-11) and LH: 9.7 mu/ml
      (n: 0.8-7.6)]. Testes ultrasounds were normal. Radiological and hormonal adrenal
      explorations were normal [Cortisol: 76 ng/ml (n: 50-250), DHEA-S: 59 MUg/ml (n:
      50-560), E2:40.2 pg/ml (n < 50)]. Body scan was normal too. The discussed
      etiologies were post radiation subclinical hypogonadism, and treatment with anti
      androgens. After flutamide withdraw, there was not any sign of prostate cancer
      recurrence, and gynecomastia decreased significantly, but did not disappear
      probably because of fibrosis. 

PMID- 23961496
TI  - Catecholamine induced cardiomyopathy in pheochromocytoma.
AB  - Catecholamine induced cardiomyopathy in the setting of pheochromocytoma is an
      unusual clinical entity. Earlier studies have reported left ventricular
      dysfunction in around 10% of subjects with pheochromocytoma.[1] Catecholamine
      induced vasoconstriction, direct toxic effect of byproducts of catecholamine
      degradation and direct receptor-mediated mechanisms are thought to contribute to
      cardiomyopathy in subjects with pheochromocytoma. The presentation remains a
      diagnostic challenge as patients may already have hypertensive heart disease and
      acute coronary syndrome on account of uncontrolled secondary hypertension. We
      report a case of a 42-year-old male, who presented with features of
      pheochromocytoma induced cardiomyopathy. 

PMID- 23961497
TI  - Hashimoto's thyroiditis associated Evans syndrome: A rare case report on the
      clustered autoimmune disease triad.
AB  - Evans syndrome is a rare combination of autoimmune hemolytic anemia and immune
      thrombocytopenia. Their association with autoimmune thyroid diseases has been
      reported by few authors; however, a sequential development of the Evans syndrome
      in cases of Hashimoto's thyroiditis is extremely rare. The clustering of these
      autoimmune diseases might share a common pathogenic pathway. We present the
      fourth such case in world literature, of a 34-year-old female diagnosed with
      Hashimoto's thyroiditis in 2006, who has been taking synthetic thyroid hormone
      since then. Her condition is now clinically complicated with the development of
      the Evans syndrome. 

PMID- 23961498
TI  - Mazabraud syndrome.
AB  - A 25 year old lady presented with pain and swelling of left thigh. On examination
      she was found to have tenderness of left femur with a separate soft tissue
      swelling within the thigh muscle. Further evaluation revealed expansile bony
      lesion on X-ray of left tibia and multiple hot spots on bone scan suggestive of
      fibrous dysplasia. The soft tissue swelling on excision and histopathological
      examination was found to be intramuscular myxoma. The combination of the above
      two, called Mazabraud syndrome is being reported. 

PMID- 23961499
TI  - Rapid development of thymic neuroendocrine carcinoma despite transcervical
      thymectomy in a patient with multiple endocrine neoplasia type 1.
AB  - Thymic neuroendocrine (NE) tumors are a rare manifestation of multiple endocrine
      neoplasia syndrome type 1 (MEN-1). They are malignant and aggressive tumors and
      form a major cause of mortality in MEN-1. Transcervical thymectomy (TCT) at the
      time of parathyroid surgery for primary hyperparathyroidism (PHPT) in MEN-1
      usually prevents thymic NE tumors. We report a 56-year-old nonsmoker male with
      sporadic MEN-1 who presented with thymic NE carcinoma developing rapidly within a
      span of 8 months after subtotal parathyroidectomy and TCT for PHPT. We present a
      brief review of literature on this rare NE malignancy, focusing on its occurrence
      despite TCT. This case highlights the fact that thymic NE carcinoma may develop
      even after TCT in MEN-1. Regular surveillance for these aggressive thymic NE
      tumors is mandatory even after TCT in MEN-1 setting. 

PMID- 23961500
TI  - Hypertensive emergency: A unique manifestation of a pituitary disorder.
AB  - Acromegaly a common pituitary disorder has significant adverse effects on well
      being and survival. The slight increase in the prevalence of hypertension in
      acromegaly is well known and is proposed to be the direct effects of growth
      hormone. The hypertension for calculating the prevalence in most series was
      defined as diastolic more than 100 mmHg, but hypertensive emergency is rarely
      ever described in the literature. Growth hormone excess has been associated with
      renal manifestations such as hypercalciuria and nephrolithiasis, but never with
      renal failure. We present a case referred to a tertiary care nephrology center
      with malignant hypertension. This is the first case of a patient of acromegaly
      presenting with hypertensive emergency progressing to malignant nephrosclerosis
      and renal failure. 

PMID- 23961501
TI  - Simultaneous presentation of giant pheochromocytoma, primary hyperparathyroidism,
      and mixed-medullary-papillary thyroid cancer in MEN 2A.
AB  - The aim of this study was to describe a young man with probably the largest
      pheochromocytoma associated with MEN 2A, described till date. The patient, a non
      vegetarian, fifth of eight siblings, married, having five children, presented
      with episodes of difficult-to-control hypertension requiring over five
      antihypertensives. He was referred to us with an abdominal CT scan that revealed
      a 16 cm left-sided adrenal mass. Biochemical testing confirmed a catecholamine
      secreting pathology. Histopathology confirmed the mass as a pheochromocytoma
      weighing 1.8 kg. Further evaluation suggested a parathormone-dependent
      hypercalcemia and a left-sided thyroid mass. Histopathology confirmed parathyroid
      hyperplasia and medullary carcinoma of the thyroid mixed with papillary carcinoma
      of thyroid. Putting all the findings together showed that the patient was
      suffering from multiple endocrine neoplasia 2. Multiple endocrine neoplasia 2A is
      a rare syndrome. The case is unique in the way it presented, with all the three
      tumors at the same time. The management was bold and addressed all the three
      lesions in the same hospital admission. We are also reporting the largest
      described case of pheochromocytoma from India. 

PMID- 23961502
TI  - A case of hemiagenesis of thyroid with double ectopic thyroid tissue.
AB  - Developmental abnormalities of the thyroid gland are very rare. The most common
      abnormalities include ectopic thyroid tissues that are commonly seen in lingual
      or sublingual location, agenesis, and hemiagenesis of the thyroid gland. These
      developmental defects may or may not be associated with thyroid dysfunction. Our
      case is an 18-year-old male who presented with swelling in the neck of 4-year
      duration. Clinical examination revealed an oval-shape swelling in the left side
      of the thyroid gland. The ultrasound and the nuclear scan report revealed the
      presence of thyroid hemiagenesis of the right lobe with isthmus along with double
      ectopic thyroid tissue at suprahyoid and infrahyoid region. His thyroid function
      test showed elevated thyroid-stimulating hormone (TSH) and normal free T4. We
      report a very rare case of thyroid hemiagenesis with double ectopic thyroid
      tissue; and to the best of our knowledge, this is the first report in the world
      literature. 

PMID- 23961503
TI  - Pituitary oncocytoma presenting as Cushing's disease.
AB  - A 19-year-old girl presented with classical features of Cushing's syndrome.
      Endocrinal evaluation was consistent with pituitary source of ACTH; but imaging
      showed normal pituitary. Bilateral inferior petrosal sinus sampling confirmed the
      diagnosis. A successful remission was achieved after adenomectomy by
      transphenoidal route. Histopathological examination was consistent with pituitary
      oncocytoma and immunohistochemistry was positive for synaptophysin, chromogranin,
      neuron specific enolase, S-100, ACTH, prolactin, and GH. 

PMID- 23961504
TI  - Cornelia de Lange syndrome.

PMID- 23961505
TI  - Mauriac syndrome: A rare complication of type 1 diabetes mellitus.

PMID- 23961506
TI  - Positive (68)Ga-DOTANOC PET/CT with negative (131)I- metaiodobenzylguanidine scan
      in a case of Glomus Jugulare.

PMID- 23961507
TI  - Gaucher disease in a 53-year-old Iranian man.

PMID- 23961508
TI  - Chronic disease: Working together.

PMID- 23961509
TI  - Prayer sign in diabetes mellitus.

PMID- 23961510
TI  - Growth hormone secreting pituitary macroadenoma and meningioma: An association or
      coincidence?

PMID- 23961511
TI  - A comment on peer support as a strategy for effective management of diabetes in
      India.

PMID- 23961512
TI  - Comment on: Shriraam et al., awareness of gestational diabetes mellitus among
      women in a primary health center in south India.

PMID- 23961513
TI  - Insulin lipodystrophy and lipohypertrophy.

PMID- 23961514
TI  - Approaching a collaborative research agenda for health systems performance in
      circumpolar regions.

PMID- 23961515
TI  - Basic dermoscopy for the resident.

PMID- 23961516
TI  - Dermatology at the University of Maryland.

PMID- 23961517
TI  - Molecular mechanisms of melanoma.

PMID- 23961518
TI  - Probiotics in acne and rosacea.

PMID- 23961519
TI  - Dermatopathology in clinical practice: avoiding abuse of self-referral and client
      billing.

PMID- 23961520
TI  - A brief primer on acne therapy for adolescents with skin of color.
AB  - The majority of adolescents with skin of color in the United States and other
      westernized civilizations develop acne vulgaris. Indigenous populations of
      children and teenagers with skin of color may not develop acne when raised on a
      paleolithic diet, suggesting the Western diet is the rudiment of acne vulgaris.
      Differences exist in the presentation of and therapy for acne in teenagers with
      skin of color, largely due to the increased risk for hyperpigmentation, scarring,
      and keloid formation, as well as style- and skin care-related exacerbating
      factors. The primary goal of acne therapy in adolescents with skin of color is
      the prevention of long-term sequelae such as keloid formation. This article
      provides a brief overview of the treatment of acne vulgaris in adolescents with
      skin of color. 

PMID- 23961521
TI  - Resolution of radiation-induced acneform eruption following treatment with
      tretinoin and minocycline: a case report.
AB  - Postradiation comedogenesis is an uncommon side effect of radiation therapy, with
      few cases reported in the medical literature. The proposed etiology of this
      reaction is alteration of pilosebaceous unit secretions and retention of
      proliferating ductal keratinocytes due to stricture and scarring. We report a
      case of a 48-year-old woman who had been treated for infiltrating ductal
      carcinoma of the right breast with lumpectomy and radiation therapy. She
      subsequently developed open and closed comedones as well as tender inflammatory
      papules and papulopustules in the irradiated area. Our patient was treated with
      tretinoin cream and oral minocycline, with rapid improvement in symptoms and
      complete resolution of lesions after 2 months of therapy. We review the
      literature on the pathogenesis, clinical features, and treatment of postradiation
      acne, and discuss rapid resolution of a radiation-induced acneform eruption after
      combination treatment with tretinoin and minocycline. 

PMID- 23961522
TI  - Rosacea fulminans.
AB  - We review rosacea fulminans, a rare condition that may cause facial scarring and
      disfigurement. All physicians and health care professionals must be aware of this
      form of rosacea to treat or refer the patient. Early treatment of rosacea
      fulminans is essential to avoid scarring. 

PMID- 23961523
TI  - Isotretinoin-induced skin fragility in a teenaged athlete: a case report.
AB  - Isotretinoin is approved by the US Food and Drug Administration for the treatment
      of severe recalcitrant nodular acne. Mucocutaneous toxicity is the most commonly
      observed side effect of isotretinoin use. Because atrophy and skin fragility may
      occur while taking isotretinoin, most warnings recommend avoidance of cosmetic
      procedures, such as dermabrasion, laser treatments, waxing, and chemical peels.
      We report a case of isotretinoin-induced skin fragility in a 16-year-old
      adolescent boy who presented with an unusual amount of skin erosions and
      excoriations on his face during wrestling season. We propose that it may be
      prudent to advise athletes who are involved in contact sports that skin fragility
      and increased erosions may occur during or after their course of treatment with
      isotretinoin. 

PMID- 23961524
TI  - Squamous cell carcinoma of the lip associated with adalimumab therapy for
      ankylosing spondylitis: a case report and review of TNF-alpha inhibitors and
      cutaneous carcinoma risk.
AB  - Adalimumab is an anti-tumor necrosis factor alpha (TNF-alpha) agent approved for
      the treatment of ankylosing spondylitis (AS); psoriatic arthritis; and moderate
      to severe cases of rheumatoid arthritis (RA), plaque psoriasis, Crohn disease,
      ulcerative colitis, and polyarticular juvenile idiopathic arthritis. Evidence
      suggests that anti-TNF-alpha agents may increase a patient's risk for some types
      of cancers, including cutaneous squamous cell carcinoma (SCC). Cutaneous
      nonmelanoma skin cancers (NMSCs) have occurred during treatment with etanercept,
      infliximab, and adalimumab in the setting of RA and psoriasis, but data related
      to AS are less clear. We report the case of a 29-year-old woman with AS treated
      with adalimumab for 2 years who developed invasive SCC of the lower lip. We
      advocate increased NMSC surveillance in patients undergoing treatment with anti
      TNF-alpha agents. 

PMID- 23961525
TI  - Infectious eccrine hidradenitis associated with intense sun exposure.
AB  - Infectious eccrine hidradenitis (IEH), which usually manifests as singular or
      multiple erythematous papules or plaques, is a rare dermatosis involving an
      infectious agent and histologic findings identical to that of neutrophilic
      eccrine hidradenitis (NEH). We report a case of IEH in a 24-year-old woman who
      developed a pruritic, erythematous, papular rash after a sunburn. A culture of a
      pustule revealed methicillin-sensitive Staphylococcus aureus. Our patient had
      complete resolution of her rash within 2 weeks of starting amoxicillin and
      clavulanate. This case of IEH and NEH related to both intense sun exposure and
      infection supports the hypothesis that NEH is a response to nonspecific stimuli
      and may occur in many different clinical settings. 

PMID- 23961526
TI  - Minocycline-induced hyperpigmentation involving the oral mucosa after short-term
      minocycline use.
AB  - Minocycline is a semisynthetic broad-spectrum tetracycline used for its
      bacteriostatic and anti-inflammatory properties in the treatment of moderate to
      severe acne vulgaris. Minocycline-induced hyperpigmentation (MIH) is a well
      recognized phenomenon documented to involve a wide array of anatomic locations
      including the skin and nails, the sclera and conjunctiva, the oral cavity, and
      the skeleton and cartilage, as well as within viscera and body fluids. Oral
      involvement typically includes the hard tissues (eg, alveolar bone, roots, crowns
      of teeth). We present a case of MIH of the labial, gingival, and lingual oral
      mucosa after only 2 weeks of treatment. Our case is unique because of the short
      course of minocycline treatment. 

PMID- 23961527
TI  - Treating acne scars in patients with Fitzpatrick skin types IV to VI using the
      1450-nm diode laser.
AB  - Individuals with Fitzpatrick skin types IV to VI are becoming a larger proportion
      of our patient base. Although acne scarring can be difficult to treat in all skin
      types, it presents a greater challenge in darker skin types due to an increased
      risk for scarring and postinflammatory hyperpigmentation (PIH). Few studies have
      focused on infrared laser treatment of acne scarring in darker skin types. In
      this study, we assess the efficacy and side-effect profile of a 1450-nm diode
      laser for the treatment of acne scars in participants with Fitzpatrick skin types
      IV to VI. Our findings show the nonablative 1450-nm diode laser to be safe and
      effective in improving the appearance of atrophic acne scars in darker skin
      types. Postinflammatory hyperpigmentation was a common occurrence. 

PMID- 23961528
TI  - Lichen planopilaris.

PMID- 23961529
TI  - What is your diagnosis? Angiolymphoid hyperplasia with eosinophilia.

PMID- 23961530
TI  - Sweet syndrome preceding a carcinoid lung tumor and multiple myeloma.

PMID- 23961531
TI  - Disappearance of seborrheic keratoses following treatment with methotrexate.

PMID- 23961532
TI  - Papular elastorrhexis.

PMID- 23961533
TI  - A basic approach to wound care.

PMID- 23961534
TI  - Identification of Dactylopius cochineal species with high-performance liquid
      chromatography and multivariate data analysis.
AB  - Identification of American cochineal species (Dactylopius genus) can provide
      important information for the study of historical works of art, entomology,
      cosmetics, pharmaceuticals and foods. In this study, validated species of
      Dactylopius, including the domesticated cochineal D. coccus, were analysed by
      high-performance liquid chromatography with a diode array detector (HPLC-DAD) and
      submitted to multivariate data analysis, in order to discriminate the species and
      hence construct a reference library for a wide range of applications. Principal
      components analysis (PCA) and partial least squares discriminant analysis (PLSDA)
      models successfully provided accurate species classifications. This library was
      then applied to the identification of 72 historical insect specimens of
      unidentified species, mostly dating from the 19th century, and belonging to the
      Economic Botany Collection, Royal Botanic Gardens, Kew, England. With this
      approach it was possible to identify anomalies in how insects were labelled
      historically, as several of them were revealed not to be cochineal. Nevertheless,
      more than 85% of the collection was determined to be species of Dactylopius and
      the majority of the specimens were identified as D. coccus. These results have
      shown that HPLC-DAD, in combination with suitable chemometric methods, is a
      powerful approach for discriminating related cochineal species. 

PMID- 23961535
TI  - A GFP-tagged nucleoprotein-based aggregation assay for anti-influenza drug
      discovery and antibody development.
AB  - Influenza is a viral pandemic that affects millions of people worldwide. Seasonal
      variations due to genetic shuffling and antigenic drifts in the influenza viruses
      have necessitated continual updating of therapeutics. The growing resistance to
      current influenza drugs has increased demand for new antivirals. The highly
      conserved nature of NP, a multi-functional viral protein that is serotypically
      distinct and abundantly expressed during infection, has led to its use in
      developing universal biotherapeutics and vaccines that could be effective against
      the virus, irrespective of its strain variations. Compounds causing aggregation
      of NP have recently been shown to be potent antivirals but require the
      development of new high-throughput assays capable of screening compounds with
      similar modes of action. Here, we describe the development of a new bioassay for
      the Influenza A nucleoprotein (NP). The assay was developed to quantify ligand
      induced aggregation of a GFP-tagged NP and was validated with aggregation
      inducing compounds such as nucleozin and a NP-specific antibody. The new NP-GFP
      aggregation assay can be performed with partially purified or mixtures of
      proteins and is amenable to a high-throughput format. Using this assay, we
      demonstrate the potential of a new anti-NP polyclonal antibody that we have
      obtained from chicken. This cost-effective high-yield source of anti-NP IgY has
      potential for large-scale production and development of therapeutic antibodies.
      The simplicity, speed and flexibility of this assay make it an invaluable tool
      for timely development of effective antivirals that can help to control future
      epidemics. 

PMID- 23961536
TI  - A highly specific BODIPY-based probe localized in mitochondria for HClO imaging.
AB  - An oxime containing fluorescent probe based on a BODIPY scaffold was successfully
      designed and used for HClO determination with rapid response, low detection
      limits and high selectivity. Confocal fluorescence microscopy demonstrated that
      the probe could permeate the mitochondria and made possible the fast fluorescent
      imaging of endogenous HClO. 

PMID- 23961537
TI  - Convenient detection of E. coli in Ringer's solution.
AB  - An easy and inexpensive detection method for DNA hybridization assays combining
      magnetic beads and enzymatically generated silver nanoparticles is introduced.
      The main advantage of this approach is the possibility to distinguish between
      positive and negative test results with the naked eye. In the case of
      complementary DNA sequences the sample will turn black within a few minutes,
      allowing readout without any hardware. In order to illustrate the applicability
      of the assay genomic DNA isolated from E. coli contaminated Ringer's solution was
      used for testing the sensitivity as well as specificity. 

PMID- 23961538
TI  - Ru-catalyzed 1,4-addition of arylboronic acids to acrylic acid derivatives in the
      presence of phenols.
AB  - [Ru(p-cymene)Cl2]2-catalyzed 1,4-addition reactions between arylboronic acids and
      butyl acrylate and acrylamide in the presence of phenols were investigated, good
      to excellent yields were obtained. The addition of phenols remarkably promoted
      the protonolysis and inhibited the beta-H elimination of the 1,4-addition
      intermediates, and also efficiently suppressed the protonolysis of arylboronic
      acids. 

PMID- 23961539
TI  - SHIfT: Ivabradine's additional clinical benefits regardless of background beta
      blocker dose.

PMID- 23961540
TI  - Creeping epidemic of obesity hits Asia Pacific  region.

PMID- 23961541
TI  - Strengths and limitations of the health-care system of Italy.

PMID- 23961542
TI  - Insomnia linked to increased risk of heart failure.

PMID- 23961543
TI  - 'Organised crime and drugs in sport': did they teach us about that in medical
      school?

PMID- 23961544
TI  - Magnet ingestion in children.

PMID- 23961545
TI  - Magnet-related injury rates in children: a single hospital experience.
AB  - BACKGROUND AND OBJECTIVE: The ingestion of multiple magnets simultaneously or the
      placement of magnets in both nares can lead to serious injury resulting from the
      attraction of the magnets across the tissues. The impact of mandatory standards
      for toys containing magnets has not been thoroughly investigated. The aim of the
      present study was to describe the emergency department (ED) visit rate for magnet
      related injuries. METHODS: We performed a retrospective study of children
      evaluated for magnet-related injuries from 1995 to 2012 in an urban tertiary care
      pediatric ED. We identified cases using a computerized text-search methodology
      followed by manual chart review. We included children evaluated for magnet
      ingestion or impaction in the ears, nose, vagina, or rectum. We assessed the type
      and number of magnets as well as management and required interventions. A Poisson
      regression model was used to analyze rates of injury over time. RESULTS: We
      identified 112 cases of magnet injuries. The median patient age was 6 years (IQR
      3.5, 10), and 54% were male. Compared to before 2006, the rate for all magnet
      related injuries in 2007-2012 (incidence rate ratio 3.44; 95% confidence interval
      2.3-5.11) as well as multiple magnet-related injuries (incidence rate ratio 7.54;
      95% confidence interval 3.51-16.19) increased. Swallowed magnets accounted for
      86% of the injuries. Thirteen patients had endoscopy performed for magnet removal
      (12%), and 4 (4%) had a surgical intervention. Magnets from toys account for the
      majority of the injuries. CONCLUSIONS: The number of ED visits for magnet-related
      injuries in children may be rising and are underreported, with an increase in the
      proportion of multiple magnets involvement. In our case series, mandatory
      standard for toys had no mitigating effect.

PMID- 23961547
TI  - Retraction statement. Effect of chemical disinfectants and repair materials on
      the transverse strength of repaired heat-polymerized acrylic resin.

PMID- 23961548
TI  - Authors' response.

PMID- 23961546
TI  - Burden of illness and use of health care services before and after celiac disease
      diagnosis in children.
AB  - OBJECTIVES: Prevalence of celiac disease in children is approximately 1%, but
      most patients remain unrecognized by reason of variable clinical presentation.
      Undetected patients may have an increased burden of illness and use of health
      care services because of nonspecific complaints. We investigated these issues
      prospectively in newly detected patients with celiac disease before and after
      diagnosis in a large nationwide cohort of children. METHODS: A validated
      questionnaire was sent to consecutive families whose children had been diagnosed
      as having celiac disease within 1 year. The survey contained questions about the
      use of medical consultations, on-demand drugs, vitamins and herbal products,
      children's absenteeism from day care or school and, parents' work absenteeism. A
      follow-up questionnaire was sent after 1 year of receiving a gluten-free diet.
      RESULTS: A total of 132 families responded. A total of 44 children were diagnosed
      because of gastrointestinal and 88 because of extraintestinal symptoms or by risk
      group screening. On treatment, outpatient visits to primary health care decreased
      from a mean of 3.0 to 1.3 visits per year (P < 0.001), the number of
      hospitalizations from 0.2 to 0.1 (P = 0.008), and antibiotic prescriptions from
      1.0 to 0.5/year (P < 0.001). Visits to secondary and tertiary health care
      increased from 0.6 to 1.4 (P < 0.001), mostly for celiac surveillance. Use of
      vitamins, micronutrients, and herbal products increased from 7.3 to 10.2 pills
      per month (P = 0.028). CONCLUSIONS: Implementation of a gluten-free diet resulted
      in reduced use of health care services and antibiotic prescriptions in children.
      Our findings support active case-finding and risk-group screening for celiac
      disease.

PMID- 23961549
TI  - Obama Administration races to meet key ACA deadline.

PMID- 23961550
TI  - Malaria and malnutrition: Niger's twin crises.

PMID- 23961551
TI  - A commitment to serve: in remembrance of Richard R. Rubin, PhD, CDE (1943-2013)
      and Harry Keen, MD (1925-2013).

PMID- 23961552
TI  - Vitamin A supplementation in Indian children.

PMID- 23961553
TI  - Spin and bias: the tip of the iceberg.

PMID- 23961554
TI  - Peter James Francis Foley.

PMID- 23961556
TI  - Life sciences: industrial immunology.

PMID- 23961557
TI  - Beyond headscarf symbolism.

PMID- 23961555
TI  - Migraine-related symptoms in childhood.
AB  - Periodic disorders of childhood often represent precursors of migraine. As we
      advance our knowledge of migraine and its complicated phenotypic presentation in
      childhood, we have noted the similarities in overlapping symptoms of children
      presenting with childhood periodic syndromes. There is often a positive family
      history of migraine in children that present with periodic syndromes. There is a
      known transformation of periodic syndromes from childhood into adult migraine
      with and without aura phenotype. There has been an evolution of our understanding
      of what was initially referred to as periodic symptoms of childhood and more
      recently been called childhood periodic syndromes and is now evolving into the
      terminology of episodic symptoms that are associated with migraine. International
      classification of headache disorders has been instrumental in the evolution of
      the classification of headache and children adults. The most recent
      classification utilizes and replaces the periodic symptom terminology with
      episodic symptoms that will no longer be limited to just childhood. This article
      will address the evolution of our understanding of the diagnostic criteria,
      pathophysiology and management of the episodic syndromes that may be associated
      with migraine.

PMID- 23961558
TI  - In addition.

PMID- 23961559
TI  - Response to letters regarding article, "Randomized comparison of sevoflurane
      versus propofol to reduce perioperative myocardial ischemia in patients
      undergoing noncardiac surgery".

PMID- 23961560
TI  - The authors respond to: Physician-ordered aerosol therapy versus respiratory
      therapist-driven aerosol protocol: effect on resource utilization.

PMID- 23961561
TI  - The authors respond to: Practice of excessive FIO2 and effect on pulmonary
      outcomes in mechanically ventilated patients with acute lung injury,.

PMID- 23961562
TI  - Uriniferous tubule: structural and functional organization.
AB  - The uriniferous tubule is divided into the proximal tubule, the intermediate
      (thin) tubule, the distal tubule and the collecting duct. The present chapter is
      based on the chapters by Maunsbach and Christensen on the proximal tubule, and by
      Kaissling and Kriz on the distal tubule and collecting duct in the 1992 edition
      of the Handbook of Physiology, Renal Physiology. It describes the fine structure
      (light and electron microscopy) of the entire mammalian uriniferous tubule,
      mainly in rats, mice, and rabbits. The structural data are complemented by recent
      data on the location of the major transport- and transport-regulating proteins,
      revealed by morphological means(immunohistochemistry, immunofluorescence, and/or
      mRNA in situ hybridization). The structural differences along the uriniferous
      tubule strictly coincide with the distribution of the major luminal and
      basolateral transport proteins and receptors and both together provide the basis
      for the subdivision of the uriniferous tubule into functional subunits. Data on
      structural adaptation to defined functional changes in vivo and to genetical
      alterations of specified proteins involved in transepithelial transport
      importantly deepen our comprehension of the correlation of structure and function
      in the kidney, of the role of each segment or cell type in the overall renal
      function,and our understanding of renal pathophysiology.

PMID- 23961563
TI  - Testing.  CDC launches campaign targeting gay Latino men.

PMID- 23961564
TI  - Programs help HIV-positive locate, receive appropriate treatment.

PMID- 23961565
TI  - Transmission.  HIV continues to spread in Europe's marginalized individuals.

PMID- 23961566
TI  - Food insecurity increases death.

PMID- 23961567
TI  - Transgender receiving proper care.

PMID- 23961568
TI  - Prisons.  HIV-positive inmate may proceed as pauper with diet charge.

PMID- 23961569
TI  - Insurance.  No indemnification for insurer sued by HIV-positive couple.

PMID- 23961570
TI  - Criminal.  Court reverses decision to dismiss unlawful sex charge.

PMID- 23961571
TI  - SSI.  Court affirms denial of disability benefits for man with HIV.

PMID- 23961572
TI  - The authors respond.

PMID- 23961574
TI  - Breast cancer surgery in Canada.

PMID- 23961573
TI  - Flap prefabrication using high-density porous polyethylene in an animal model -
      an experimental study.
AB  - BACKGROUND: The search for new surgical flap techniques and modifications of
      already existing ones is gaining increasing popularity. Progress in flap
      designing and harvesting have improved the functional and aesthetic results,
      especially in head and neck reconstruction. MATERIAL/METHODS: Ten pigs were used
      in this study. In the first operation, high-density porous polyethylene
      prefabrication was performed bilaterally in all pigs. After 8 weeks, each
      prefabricated complex was explored, resected, and macroscopically evaluated.
      RESULTS: All of 20 prefabricated flaps survived. No serious surgical
      complications were observed. In 2 cases there was chronic inflammation and in 4
      cases there was instability of the implant. CONCLUSIONS: After this experimental
      study, we believe that the use of high-density porous polyethylene in flap
      prefabrication may be a good option for reconstruction of 3-dimensional defects,
      especially in patients with limited donor tissues.

PMID- 23961575
TI  - An interview with Professor Yasumasa Akagawa. Interview by Yoshinobu Maeda and
      Kiyoshi Koyano.

PMID- 23961576
TI  - Inappropriate continuation of stress ulcer prophylaxis beyond the intensive care
      setting.
AB  - OBJECTIVE: To determine how frequently stress ulcer prophylaxis (SUP) medications
      prescribed in the intensive care unit are inappropriately continued on the ward
      and on hospital discharge. DESIGN: Retrospective cohort study; chart review.
      SETTING: Two Australian ICUs: one tertiary centre and one metropolitan centre.
      PARTICIPANTS: We included 387 adult, non-pregnant patients who were admitted to
      the ICU between 1 February 2011 and 31 March 2011 and who survived to hospital
      discharge. MAIN OUTCOME MEASURES: Rate of unnecessary continuation of ICU
      prescribed SUP medications on the ward and on discharge from hospital. RESULTS:
      While in the ICU, 329 of the 387 patients (85%) were prescribed SUP medications.
      Of the 233 patients who had not been taking acid-suppressive medications before
      admission to the ICU, 190 were prescribed SUP medications in the ICU. Of these
      190 patients, most (63%) had their SUP continued in the ward without any obvious
      indication, and many (39%) had their SUP medications inappropriately continued on
      discharge from hospital. CONCLUSIONS: SUP medications commenced in ICU are
      frequently continued unnecessarily, both in the wards and hospital discharge.

PMID- 23961577
TI  - Current world literature. Neuroendocrinology.

PMID- 23961578
TI  - GI jobs: states are helping veterans find good jobs based on the training and
      education they received in the military.

PMID- 23961579
TI  - TMI? not in today's health care world.
AB  - Everybody wants health care providers to better engage patients and their
      families. But wanting it to happen and making it happen are two different things.

PMID- 23961580
TI  - A high-value network for Medicare.

PMID- 23961582
TI  - In the game. Making a game of improving health and wellness.

PMID- 23961581
TI  - Getting the word out. Ramping up for the Oct. enrollment push.

PMID- 23961583
TI  - Mayo Clinic offers hockey rehab and training.

PMID- 23961584
TI  - mHealth: Managing data on the go.

PMID- 23961585
TI  - Keeping costs down. Massachusetts trying to force costs lower.

PMID- 23961586
TI  - 2013 most wired.
AB  - H&HN's 15th annual survey shows U.S. hospitals have made big strides in laying
      the foundation for robust clinical information systems. The next step: harnessing
      IT for the real work of improving care delivery.

PMID- 23961587
TI  - Challenging the community. Interview by Marty Stempniak.

PMID- 23961588
TI  - New blood for your board.
AB  - Baby boomers dominate hospital boards today. Here's how CEOs and board leaders
      are attracting younger trustees, who can offer fresh perspectives and maintain
      continuity when older members leave.

PMID- 23961589
TI  - Hospitals to docs and moms: don't rush the baby.
AB  - Hospitals are working to reduce early elective deliveries and cut the chance for
      harm to infants and mothers. Convincing physicians and women can be difficult;
      some hospitals have gone so far as to implement "hard stops.

PMID- 23961591
TI  - Cow costume not (always) required.

PMID- 23961590
TI  - Patient-centered care.

PMID- 23961592
TI  - Transforming clinical purchasing.

PMID- 23961593
TI  - When diabetes hits home.

PMID- 23961595
TI  - Cooking 101: low-sodium cooking.

PMID- 23961594
TI  - Probiotics: a new tool for oral health.

PMID- 23961596
TI  - Resolving diabetes-related bladder problems.

PMID- 23961597
TI  - Canagliflozin: a new drug for type 2.

PMID- 23961598
TI  - Diabetes quiz. How much do you know about protein?

PMID- 23961599
TI  - Avoiding medical identity theft.

PMID- 23961600
TI  - What your doctor is reading.

PMID- 23961601
TI  - Supermarket smarts. Bread spreads.

PMID- 23961602
TI  - [Surgical treatment of shoulder instability].
AB  - Most commonly, shoulder instability results from a traumatic dislocation of the
      shoulder joint, usually happening to men under the age of 30. The first
      uncomplicated dislocation is treated conservatively. Instability refers to
      symptomatic instability of the shoulder joint, i.e. recurrent dislocations or
      fear of dislocation. Clinical examination and X-ray are usually sufficient for
      diagnosis. While mechanical instability of the shoulder joint is an indication
      for surgery, the operative technique should be selected in a patient-specific
      manner.

PMID- 23961603
TI  - [Diffusion tensor imaging and sequel of brain injury].
AB  - By observing the magnitude and direction of thermal motion of water molecules,
      diffusion tensor imaging (DTI) allows the study of the internal structure and
      disturbances of the white matter tracts. For instance in neurosurgery, the
      relation of the corticospinal tract to the tumor to be operated can be defined in
      this manner when planning the operation. It is hoped that DTI will be beneficial
      for patients who are not recovering from brain injury in an expected manner,
      although conventional imaging methods do not reveal any brain damage. Indeed, DTI
      is able to distinguish brain-damaged patients from healthy controls also in cases
      of a normal MRI finding.

PMID- 23961604
TI  - [Multiple sclerosis and pregnancy].
AB  - Multiple sclerosis will usually calm down during pregnancy, but the number of
      relapses again increases immediately after childbirth. Among the conventional
      immunomodulatory drugs, there is experience already for over 15 years of the use
      of interferon-beta and glatiramer. No indications of harmful effects on the fetus
      have been noted, and interferon-beta and glatiramer can very likely be safely
      used until the beginning of pregnancy. Fingolimod is suspected to be harmful for
      fetal development, and the use of this drug should be stopped no later than two
      months before discontinuing the contraception.

PMID- 23961605
TI  - [Takotsubo cardiomyopathy].
AB  - Takotsubo cardiomyopathy resembles cardiac infarction in its clinical picture,
      but without the presence of coronary artery stenosis. Most patients are
      postmenpausal women. Dysfunction of the autonomic nervous system and an excess of
      catecholamines - most likely adrenaline - are considered to be the cause of the
      syndrome. A contrast examination is essential to exclude coronary artery disease,
      and it will actually reveal a motion disturbance typical of takotsubo
      cardiomyopathy. Beta blocker medication is preserved, although it will not
      completely protect form relapse. The prognosis is good, and the cardiac motion
      disturbance usually recedes in 4 to 6 weeks.

PMID- 23961606
TI  - [Beta-hemolytic streptococcal bacteremia in adults].
AB  - The serogroups A (Streptococcus pyogenes), B (Streptococcus agalactiae) and S.
      dysgalactiae subsp. equisimilis (group C and G) are generally defined as beta
      hemolytic streptococci. Beta-hemolytic streptococci cause a variety of infections
      ranging from skin and soft-tissue infections to severe invasive infections such
      as necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS). The
      case fatality rate due to bacteremias caused by beta-hemolytic streptococci is
      15%. The use of clindamycin in combination with benzylpenicillin has been shown
      to be of benefit. The use of intravenous immunoglobulin is suggested in STSS in
      combination with antibiotics and surgery.

PMID- 23961607
TI  - [Biliary atresia].
AB  - Biliary atresia is a rare, neonatal, progressive cholestatic liver disease caused
      by fibroinflammatory obstruction of the biliary tree. Typical symptoms include
      prolonged neonatal jaundice, pale stools, and conjugated hyperbilirubinemia.
      Treatment starts with portoenterostomy, where fibrotic remnants of the extra
      hepatic bile ducts are replaced with small intestine. Best operative results are
      achieved among the youngest patients treated in specialized centres. Despite
      clearance of jaundice after a successful operation, fibrotic change of the liver
      continues in most. Liver transplantation serves as a salvage procedure if the
      portoenterostomy fails, or complications of liver cirrhosis develop after an
      initially successful portoenterostomy. In Finland, biliary atresia treatment was
      centralized in 2005. Of the patients treated thereafter, 90% are alive and over
      80% with their native livers.

PMID- 23961608
TI  - [Bilateral failure of the vestibular system of the inner ear underlying an
      equilibrium disturbance].
AB  - Bilateral vestibular failure is a fairly rare, though possible cause underlying
      the symptoms of a dizzy patient. A recognizable oscillopsia symptom makes the
      diagnosis easier, though confirmation of the diagnosis requires a more precise
      measurement. The prognosis for recovery is not good, and curative treatment is
      not available. Diagnosis is nevertheless important with regard to rehabilitation
      and maintaining of functional capacity.

PMID- 23961609
TI  - [Lobotomy].
AB  - Lobotomy was the first psychosurgical method which aroused interest. It was
      developed by Antonio Egas Moniz in 1935. Lobotomy was understood to be a
      promising treatment in schizophrenia and in 1940-ies and -50-ies about 1600
      patients were operated in Finland. In 1960-ies psychopharmacas set aside the
      operation. The lobotomized brain, radiological and neuropathological documents of
      the operation are destined to disappear.

PMID- 23961610
TI  - Center of Cleft Lip-Cleft Palate and Craniofacial Deformities, Khon Kaen
      University in association with "Tawanchai Project" and Faculty of Medicine, Khon
      Kaen University. Foreword.

PMID- 23961611
TI  - Factors related to tooth loss due to dental caries among workers in an industrial
      estates in Thailand.
AB  - OBJECTIVE: The present study aimed to evaluate the prevalence and factors related
      to tooth loss due to dental caries among workers in industrial estates in
      Pathumthani and Phranakhorn Si Ayutthaya provinces in central Thailand. MATERIAL
      AND METHOD: The present study utilized quantitative and qualitative
      methodologies. A quantitative study was done using a cross-sectional analytic
      method with a sample group of 457 adults (283 males; 174 females) between 19 and
      53 years. Data were obtained through an oral examination and oral health behavior
      questionnaire. Data analyses were done using descriptive, bivariate and
      multivariable logistic regression statistics. In-depth interviews were used to
      collect qualitative data from 11 subjects. RESULTS: Most (62.2%) participants had
      tooth loss due to caries and findings from the final multivariable logistic
      regression model revealed that such loss was associated with education,
      residency, use of social security welfare, decayed teeth and filled teeth.
      Relatedly, the in-depth interview confirmed that tooth loss due to dental caries
      was related to (1) lack of time to visit a dentist (2) have a negative attitude
      toward or a phobia regarding dental treatment (3) inability to afford the high
      cast of dental treatment (4) lack of knowledge in regarding dental caries
      prevention, root canal treatment and the harmful effects of losing teeth (5)
      choosing to get an extraction upon having caries exposed pulp and (6) lack of
      oral health promotion programs provided by either the government or private
      sectors. CONCLUSION: The government and non-government organizations should
      promote oral health in an industrial estates and provide services and welfare for
      dental health of workers in an industrial estate appropriate to their socio
      economic needs.

PMID- 23961612
TI  - Laparoscopic appendectomy: results of a new technique for stump management.
AB  - OBJECTIVE: The purpose of the present study was to review a new laparoscopic
      technique for treatment of appendicitis. An earlier pilot study indicated the
      safety of the technique in addition to saved time and cost. MATERIAL AND METHOD:
      The electronic records were analyzed on appendix surgeries performed at our
      hospital between January 1, 2007 and December 31, 2011. RESULTS: The 91 patients
      who had an appendiceal stump closure using clips (viz., the Hem-o-lock clip) had
      a significantly shorter surgery and hospitalization than those whose appendiceal
      stump was closed using the standard loop strap (Endo-loop). CONCLUSION: The
      complications between groups were not significantly different and were treated in
      both groups using conservative management.

PMID- 23961613
TI  - Laparoscopic vesicovaginal fistula repair: a novel approach.
AB  - BACKGROUND: Vesicovaginal fistula (VVF) is a common consequence of gynecologic
      procedures. Treatments include transabdominal, transvaginal and laparoscopic
      surgery. New methods for laparoscopic VVF repair aim to improve treatment
      outcomes and reduce post-operative complications. OBJECTIVE: To report a novel
      approach for laparoscopic VVF repair. MATERIAL AND METHOD: Medical records were
      reviewed of 5 patients who underwent a novel approach for laparoscopic VVF repair
      for benign fistula between October 2008 and December 2010. None had previously
      undergone operative repair Preoperative cystoscopy revealed supratrigonal VVFs in
      all patients. Each patient was placed in the lithotomy position and four or five
      trocars used. Cystoscopy combined with laparoscopy was performed to identify the
      site of the fistula. Limited cystotomy was done and the fistula tract excised.
      The bladder and vagina were closed independently and the omentum interposed
      between them. RESULTS: All cases were successfully managed using the laparoscopic
      technique. The respective mean operative time and length of hospital stay was 229
      min (range, 150-300) and mean 4.4 days (range, 4-6). All patients were able to
      take food and drink within a day of surgery. The post-procedural cystogram showed
      no leakage. The urethral catheter was removed after 24.4 days (range, 18-34
      days). CONCLUSION: Laparoscopic transperitoneal repair of VVF is a feasible and
      safe technique, Cystoscopy combined with laparoscopy simplifies limited
      cystotomy.

PMID- 23961614
TI  - Quality of life after donor nephrectomy for living donor kidney transplantation
      at Srinagarind Hospital.
AB  - OBJECTIVE: To determine the quality of life (QoL) of donors who have undergone
      nephrectomy for living donor kidney transplantation at Srinagarind Hospital,
      using the Thai version of the Short-Form, 36-item, health survey (SF-36).
      MATERIAL AND METHOD: The SF-36 questionnaires were sent by mail to 93 living
      donors who underwent nephrectomy between Jan 1, 1990 and Dec 31, 2008. The first
      part collected demographic data and the donor/recipient relationship, the second
      surveyed QoL, and the third asked about decision-making, donation-related stress
      and feedback. RESULTS: Forty-nine questionnaires were returned completed (30
      women; 19 men: mean age 44.2 +/- 9.5 (range, 28-65) years). Thirty-one
      participants (61%) were siblings of the recipients. The QoL scores were not
      significantly different from the general Thai population; albeit nominally higher
      for mental health and social function. Upon reflection, only 5 (10%) had second
      thoughts. CONCLUSION: Donor nephrectomy did not affect QoL; thus, from that
      perspective living kidney transplantation is a suitable procedure for donors.

PMID- 23961615
TI  - Laparoscopic simple nephrectomy: perioperative outcomes at Srinagarind Hospital.
AB  - BACKGROUND: Laparoscopic urology is a minimally invasive alternative to open
      surgery, especially laparoscopic simple nephrectomy for benign disease such as
      KUB stone. OBJECTIVE: To evaluate the efficacy and perioperative outcomes of
      laparoscopic simple nephrectomy at Srinagarind Hospital. MATERIAL AND METHOD:
      Analyzed the demographic and perioperative data of 78 consecutive patients who
      underwent laparoscopic simple nephrectomy. RESULTS: Mean age was 54.1. The
      indications included non-functioning kidney (64) and infection (14). Surgery
      averaged 118.37 minutes. In 38 and 40 respective cases, a transperitoneal and
      retroperitoneal approach was used. Intraoperative complications (13; 16.7%)
      included 10 bleeding, 2 diaphragmatic injuries and 1 pancreatic injury. Six cases
      (10.3%) were converted to open surgery: 5 for massive adhesion and 1 for
      uncontrolled bleeding. Mean estimated blood loss was 170.99 ml. Post-operative
      complications included: 8 cases of prolonged ileus and 5 wound infections. Mean
      post-operative analgesia was 14.0 mg morphine: mean pain score at post-operative
      day 1 6.20. Mean time to oral intake was 1.48 days, and post-operative period
      4.63 days. Retroperitoneal access was associated with: shorter operative time
      (103.83 vs. 133.68 minutes, p = 0.008); a better result vis-a-vis post-operative
      ileus (1 vs. 7, p = 0.021); and shorter time to oral intake than transperitoneal
      route (1.20 vs. 1.79 days, p = 0.004). CONCLUSION: Vis-a-vis reducing pain,
      faster recovery and improved cosmetics laparoscopic nephrectomy by a skilled
      surgeon via retroperitoneal approach is preferred for benign diseases.

PMID- 23961616
TI  - A comparison of the Acute Physiology and Chronic Health Evaluation (APACHE) II
      score and the Trauma-Injury Severity Score (TRISS) for outcome assessment in
      Srinagarind Intensive Care Unit trauma patients.
AB  - OBJECTIVE: To assess the ability of the Acute Physiology and Chronic Health
      Evaluation (APACHE II) system and Trauma-Injury Severity Scoring (TRISS) system
      in predicting group mortality in intensive care unit (ICU) trauma patients.
      MATERIAL AND METHOD: The trauma patients admitted to ICU at Srinagarind Hospital
      between June 2008 and December 2010 were studied. For each patient, demographic
      data, mechanism of injury and surgical status were collected. The probability of
      death was calculated for each patient based on the APACHE II and TRISS equations.
      The ability to predict group mortality for APACHE II and TRISS was assessed by
      receiver operating characteristic curve analysis, two by two decision matrices
      and calibration curve analysis. RESULTS: One hundred and thirty-two trauma
      patients were admitted to the ICU. Twenty-seven (20%) patients died and hundred
      and five (80%) survived. There were significant differences between survivors and
      non-survivors in Glasgow Coma Scale, Revised Trauma Score, Injury Severity Score
      and APACHE II score. By receiver operating characteristic (ROC) curve analysis,
      the areas under the curves (+/- SEM) of APACHE II and TRISS were 0.89 +/- 0.04
      and 0.83 +/- 0.04, respectively. Using two by two decision matrices with a
      decision criterion of 0.5, the sensitivities, specificities and percentages
      correctly classified were 44.4%, 98.1% and 87.1%, respectively for APACHE II and
      25.9%, 98.1% and 83.3%, respectively, for TRISS. From the calibration curves, the
      r2 value was 0.99 (p = 0.0001) for APACHE II and 0.98 (p = 0.0001) for TRISS.
      CONCLUSION: Both APACHE II and TRISS scores were shown to accurately predict
      group mortality in ICU trauma patients. APACHE II and TRISS may be utilized for
      quality assurance in ICU trauma patients. However, neither APACHE II nor TRISS
      provides sufficient confidence for prediction of outcome of individual patients.

PMID- 23961617
TI  - Laparoscopic nephrectomy in children: experience at Srinagarind Hospital, Khon
      Kaen University.
AB  - BACKGROUND: Laproscopic nephrectomy has become a popular procedure since first
      being introduced in 1990. OBJECTIVE: Evaluate the feasibility and efficacy of
      laparoscopic pediatric nephrectomy. MATERIAL AND METHOD: The authors reviewed the
      in-patient medical records at Srinagarind Hospital, Khon Kean University between
      2007 and 2011. Laparoscopic nephrectomy was performed on 9 pediatric patients.
      The demographic data, indications for surgery, route of approach and peri
      operative outcomes were analyzed. RESULTS: Ten nephrectomies (6 L; 4 R) were
      performed on the nine patients (mean age 8.8 years: 7 males; 2 females). One
      patient underwent a bilateral nephrectomy at a different time. A trans-and retro
      peritoneal approach was used on 1 and 9 cases, respectively. The respective mean
      operative time and hospital stay was 108.8 minutes and 5.8 days. The mean
      estimated blood loss was 31.8 ml (minimal-100 ml): no blood transfusion was
      required. Post-operatively, there were no major complications and the mean pain
      score was 2.3 (0-5). Only one patient was converted to an open nephrectomy and
      that due to massive adhesion. CONCLUSION: Laparoscopic pediatric nephrectomy has
      been a feasible and safe procedure at our institution.

PMID- 23961618
TI  - Prevalence of prostate cancer in northeastern Thailand.
AB  - BACKGROUND: Prostate cancer is a major problem and the prostatic specific antigen
      (PSA) blood test is the most effective test for early detection. There is,
      however, a paucity of confirmatory prevalence data for the Thai population.
      OBJECTIVE: To determine the prevalence of prostate cancer in the northeastern
      region of Thailand. MATERIAL AND METHOD: This was a cross-sectional study at the
      Health Check-up Clinic of Srinagarind Hospital between July 2008-2009. Recruits
      included 129 patients > 45 years of age. Prostatic specific antigen (PSA) was
      measured and patients with a high PSA level were counseled to undergo a
      transrectal ultrasound (TRUS)-guided biopsy. The cancer detection rate was
      calculated and the specificity of the diagnostic test determined using the ROC
      curve. The Spearman correlation between the PSA level and the Gleason score was
      established. RESULTS: The respective mean age and PSA level was 61 and 2.3 ng/ml.
      Thirteen patients had a PSA level > 4 ng/ml; all of whom underwent TRUS-guided
      biopsy; eight were positive for prostate adenocarcinoma. The prevalence of
      prostate cancer was thus 6.2% (8/129 patients). The specificity of the cut-off
      PSA level at 4 ng/ml as per the ROC curve was 40%. There was no correlation
      between the PSA level and the Gleason score. CONCLUSION: The prevalence of
      prostate cancer was 6.2%. According to the ROC curve, a cut-off PSA level of 4
      ng/ml would be an appropriate for prostate cancer screening among Thai males.

PMID- 23961619
TI  - Growth modification in unilateral cleft lip and palate patients with face mask.
AB  - The intended aim of treatment in cleft lip and palate patients with growth
      modification is to improve the relation of jaws by advance the maxilla, restrict
      the mandible or combination of these. The appliances usually used are face mask
      or protraction headgear (Delaire and Petit types). Modification of growth is
      advocated to be applied before the end of adolescent growth spurt and long-term
      and permanent improvement cannot be guaranteed. Achieving the aim of growth
      modification is still controversial since most reported results of this treatment
      are dento-alveolar changes and backward rotation of the mandible that would not
      be considered to be growth modification.

PMID- 23961620
TI  - Nursing care system development for patients with cleft lip-palate and
      craniofacial deformities at Srinagarind Hospital.
AB  - BACKGROUND: A holistic nursing care system for patients with cleft lip-palate
      (CLP) and/or craniofacial deformities was arranged by the Nursing Department,
      Srinagarind Hospital, which provides tertiary nursing care. The nursing care
      system was developed as per system theory via participating management with
      action research following the Deming Cycle (PDCA) divided into 3 phases.
      Participants included 117 nurses from 8 divisions caring for patients with CLP
      and 128 parent caregivers. The research instruments included: 1) situation
      analysis, 2) meeting and planning and 3) self-administered questionnaire. Groups
      were divided according to the age, physical and mental aspects of the patients.
      RESULTS: 1) The nursing care system under study comprised psychosocial care,
      breastfeeding, counseling, providing assistance in various ways in order to
      respond to problems of patients/families by the multidisciplinary team. There was
      also follow-up to evaluate the results and in order to give patients/families
      longitudinal and continuing care. 2) Minor research of 4 nursing sections was
      initiated. 3) Nursing care standards, manuals, regulations and innovations for
      the organization of eight nursing sections were created and implemented.
      CONCLUSION: The present study on developing a nursing care system for patients
      with CLP helped the team to (a) understand the overall nursing care system (b) to
      develop the organization of nurses by conducting research and (c) to create 12
      works for developing care. The latter aimed to establish or create standards,
      nursing manuals, caring manuals, regulations, innovations, CDs, portfolios and
      informative cartoons to be applied systematically and shared across and between
      communities. The model for nursing care for patients with CLP in tertiary
      hospitals was clearly demonstrated.

PMID- 23961621
TI  - The development of the nursing care system for patients with cleft lip-palate and
      craniofacial deformities at Tawanchai Cleft Center, Srinagarind Hospital, Khon
      Kaen, Thailand.
AB  - BACKGROUND: The highest incidence of cleft lip-palate and craniofacial
      deformities in Thailand occur in the Northeastern Region. There is the necessity
      for an interdisciplinary care team as well as the specialized care center with
      systematic coordinated care, thus "Tawanchai Cleft Center" is becoming a superior
      medical center for patients with cleft lip-palate and craniofacial deformities.
      Therefore, the development of the nursing care system for patients with cleft lip
      palate and craniofacial deformities at Tawanchai Cleft Center, Srinagarind
      Hospital is extremely important and necessary. OBJECTIVE: To develop the nursing
      care system appropriate for a super tertiary hospital (Tawanchai Cleft Center).
      MATERIAL AND METHOD: It is a participation study which has 3 steps as follows, 1)
      Analyzing the situations and collecting the opinions of the 22 Out-patient
      Surgery Department staff and Tawanchai Cleft Center staff by using 6 questions,
      2) Summarizing of the situation analysis from the meetings and the
      questionnaires, then using such summary as the guidelines for developing the
      nursing care system from January 2011 onwards, 3) evaluating the satisfaction
      after the 4 month development period (May-August 2011) with 106 caregivers by
      using 8 questions and being analyzed by the average value, percentage and
      standard deviation. RESULTS: 1) The nursing care system consisted of psychosocial
      care, breast feeding, counseling and other assistance as required. This various
      assistance responded to the patient/family problems by following the treatment
      guideline of the multidisciplinary team which uses the continuous evaluation
      processes for the holistic patient/family care. 2) The patients with complete
      cleft lip-palate were the most common type, found in 44 cases or 41.53 percent.
      The highest number of caregivers were mothers which were 68 percent; the average
      age of those mothers was 36 years old. The highest number of them finished
      elementary school at 43 percent and 40 percent were farmers. The satisfaction for
      the services of Tawanchai Cleft Center showed the average for each satisfaction
      subject all at very good level (x = 3.56, SD = 0.13). CONCLUSION: The care for
      patients with CLP and craniofacial deformities at Tawanchai Cleft Center
      Srinagarind Hospital has been developed in order to have the appropriate nursing
      care system to provide superior quality care, which provides patient-holistic
      care, as well as improving effective accessibility to the services. Thus, the
      patients/caregivers who are satisfied with given services, get continuing
      monitoring and treatment and are able to live their lives in the society happily.

PMID- 23961622
TI  - Nursing outcome in patients with craniofacial anomalies who underwent operation.
AB  - BACKGROUND: The Northeast of Thailand has patients with craniofacial anomalies
      about 2.5: 1,000 children birth. Ward 3C Srinagarind Hospital has about 150-200
      cases of patients with craniofacial anomalies each year. Some of them have an
      operation about 10 times. When the patients go to hospital to undergo operation,
      patients and families experience fear and anxiety. They need information about
      their disease, operation, feeding and wound care. Nurses who work continuously
      and closely with the patients need to have ability to support patients needs by
      using nursing process. Nursing outcome will help nurses to measure the quality of
      nursing care. OBJECTIVE: To study nursing outcome in the patients with
      craniofacial anomalies who were admitted in 3C ward. MATERIAL AND METHOD: The
      present study is retrospective descriptive study. Data was collected from medical
      records of 27 patients with craniofacial anomalies who were admitted in 3C ward
      Srinagarind Hospital between June 2010 to May 2011. Medical records were
      purposively selected for the study and recorded with a data collection form.
      RESULTS: The authors found that 2.36% of patients had wound infection. 100% of
      parents received information about disease, medication, self care but some
      information was not received or was received but not understand. 1 case of
      patients unplanned readmit. Length of stay of patient 2.74 days. Parents
      satisfaction is 91.81%. CONCLUSION: Patients had wound infection when back home
      because care giver cannot clean patients wound correctly, parents and care giver
      did not receive enough information or did not understand all information.

PMID- 23961623
TI  - Comparison of the reliability of parental reporting and the direct test of the
      Thai Speech and Language Test.
AB  - OBJECTIVE: To find reliability of parental or caregiver's report and testing of
      the Thai Speech and Language Test for Children Aged 0-4 Years Old. MATERIAL AND
      METHOD: Five investigators assessed speech and language abilities from video both
      contexts: parental or caregivers' report and test forms of Thai Speech and
      Language Test for Children Aged 0-4 Years Old. Twenty-five normal and 30 children
      with delayed development or risk for delayed speech and language skills were
      assessed at age intervals of 3, 6, 9, 12, 15, 18, 24, 30, 36 and 48 months.
      RESULTS: Reliability of parental or caregivers' testing and reporting was at a
      moderate level (0.41-0.60). Inter-rater reliability among investigators was
      excellent (0.86-1.00). CONCLUSION: The parental or caregivers' report form of the
      Thai Speech and Language test for Children aged 0-4 years old was an indicator
      for success at a moderate level. Trained professionals could use both forms of
      this test as reliable tools at an excellent level.

PMID- 23961624
TI  - Reliability of perceptual assessment for resonance disorders in patients with
      cleft palate.
AB  - OBJECTIVE: Determine reliabilities of perceptual assessment of resonance
      disorders in people with cleft palate. MATERIAL AND METHOD: A prospective study
      of inter- and intra-rater reliability of perceptual screening assessment of
      resonance disorders with 6-scale and 2-scale criteria among 19 speech and
      language pathologists (SLPs) from 30 connected speech samples of children with
      cleft palate aged 4-17 years via video recorder when compared to principle
      investigators. RESULTS: The percentage of agreement of inter-rater ranged from
      23.33-100.00 while Kappa's coefficients was 0.08-0.67. For intra-rater
      reliability, the present study showed the percentage of agreement ranged from
      46.67-100, Kappa's coefficient was 0.17-1. It seems that the more number of years
      experiences as an SLP, the better listening skill. CONCLUSION: Reliabilities of
      perceptual assessment of resonance varied widely but it appears that listening
      skill might be directly related to experiences. Training programs for critical
      listening skills are needed.

PMID- 23961625
TI  - Development of speech services for people with cleft palate in Thailand: lack of
      professionals.
AB  - Cleft lip/palate is one of the most common birth defects and has a high incidence
      in Thailand. Most children with cleft still have social stigma from speech and
      language defects after surgical treatment. Speech and language therapies are
      required at an early age and require long-term care until teenager or adult.
      Unfortunately, there are insufficient speech services for cleft because of a lack
      of qualified speech and language pathologists in Thailand. Development consisted
      of two remedy modalities of bottom-up and top-down models, Community-Based Speech
      Therapy Model for people with Cleft Lip Cleft Palate including networking and
      standard assessments of both subjective and objective measurements. That might be
      the best and most suitable way to solve problems of lacking speech services in
      Thailand or developing countries which have similar contexts.

PMID- 23961626
TI  - Development outcomes of Thai children with cleft lip/palate at 5-years-old.
AB  - OBJECTIVE: To measure the development outcomes among Thai children with non
      syndromic cleft lip and/or palate (CLP) treated at the Tawanchai Center 5 years
      after birth. MATERIAL AND METHOD: Using a developmental screening test, Thai
      children with CLP were followed-up at the center. RESULTS: Nearly two-thirds
      (62.5%) of 24 Thai children with CLP had delayed development. Eight of the
      children had more than one delayed category and 13 both "delayed" and "caution".
      Delayed language, personal, social and fine motor skills occurred in 54.2%, 20.8%
      (5/24) and 20.8% (5/24) of cases, respectively. CONCLUSION: An understanding of
      the incidence of the different types of delays will help our center to improve
      our treatment standards and place more emphasis on psychosocial and development
      outcomes.

PMID- 23961627
TI  - Audiological status in patients with cleft lip and palate at Srinagarind
      Hospital.
AB  - OBJECTIVE: To determine the audiological status in patients with cleft lip and
      palate. STUDY DESIGN: A descriptive retrospective study. MATERIAL AND METHOD:
      Data were retrieved from hospital records of 234 patients with cleft lip and
      palate and cleft palate who underwent hearing assessment between June 2007 and
      September 2010 at Srinagarind Hospital, Khon Kaen University. Descriptive data of
      the audiological evaluation were presented. RESULTS: Unilateral or bilateral
      hearing loss at the first hearing assessment was encountered among 186 patients
      (79.49%). Among these, 165 (88.71%) had bilateral conductive hearing loss and 16
      (8.6%) had unilateral conductive hearing loss. The degree of hearing loss was
      greatest to a moderate degree in 181 (50.84%) ears. Most tympanometric
      evaluations presented with type B (335 ears or 72.67%). The age of the patient
      was significantly correlated with audiological status. CONCLUSION: The current
      study showed that there is a high prevalence of hearing impairment among patients
      with cleft lip and palate and cleft palate. Therefore, routine audiological
      assessment should be performed as early as possible, especially among children.
      Further prospective investigation of the prevalence of hearing loss in children
      with cleft lip and palate and cleft palate should be considered, and endorsed as
      a national healthcare policy priority in order to raise awareness and to prevent
      hearing loss among these children.

PMID- 23961628
TI  - Relationship of perceptual evaluation for resonance disorders to nasalance scores
      in children with cleft palate.
AB  - OBJECTIVE: To determine relationship between screening perceptual assessment for
      resonance disorders and nasalance scores. MATERIAL AND METHOD: Screening
      perceptual assessment of 115 children with cleft palate with or without lip was
      performed to determine its relationship to nasalance sores. The perceptual
      assessment 3-scale (-1: hyponasality; 0: normal; +1: hypernasality) was compared
      to nasalance scores based on nasometry. To find the weight of Kappa, nasalance
      scores were converted to a 3-ordinal scale with 3 criteria for cut-off points (
      1: nasalance score -1, -1.5 and-2 SD lower than the mean, 0: nasalance score +/-
      1 SD, +/- 1.5 and +/- 2 SD of the mean; and + 1: nasalance score + 1 SD, + 1.5,
      and + 2 SD greater that the mean). RESULTS: Correlations between screening
      perceptual assessment and nasalance scores were good to excellent. The percentage
      of agreement was good, the Kappa reliability was fair to moderate in passages of
      a mixture of oral and nasal consonants (My House) and devoid of nasal consonants
      (Laying Hen). A weak relationship was found for the nasal passage (Winter).
      CONCLUSION: The relationship of speech assessments in the present study varied,
      as it depended on the different variables and analysis. To ensure a strong
      relationship, further prospective study is needed.

PMID- 23961629
TI  - Temporomandibular joint growth adaptation and articular disc positional changes
      in functional orthopedic treatment: magnetic resonance imaging investigation.
AB  - Functional orthopedic appliances have been proposed for the correction of Class
      II malocclusion due to a retrognathic mandible. The aim of using this appliance
      is to stimulate mandibular growth by forward positioning of the mandible in order
      to achieve normal jaw relationship. However, the modes of action using this
      appliance are still inconclusive. Also the effects of this therapy on the
      temporomandibular joint (TMJ) are still subject to doubts and discussion.
      Magnetic resonance imaging (MRI), the gold standard for assessing the soft tissue
      and position of the TMJ articular disc, therefore, was used to help clarify the
      effect of this appliance on the TMJ. The aims of this article are to provide a
      literature review of the methods that are used to assess changes in the TMJ, as
      seen on MRIs, from functional orthopedic appliances which include condylar and
      glenoid fossa remodeling assessment, condyle-fossa relationship assessment and
      articular disc assessment and to review clinical studies using MRI to investigate
      the effects of functional orthopedic treatment on the TMJ.

PMID- 23961630
TI  - Nursing outcome in patients with cleft lip and palate who underwent operation:
      follow-up cases.
AB  - BACKGROUND: Cleft lip and cleft palate are the most common craniofacial anomalies
      affecting approximately 2.5 of every 1,000 children born in North East of
      Thailand. Srinagarind Hospital has 150-200 cases of cleft lip and palate each
      year. The lengthy treatment process of care, requires continuity of care
      involving a multidisciplinary team. The holistic and interdisciplinary care is
      very important to patients, family, health care professionals and the health care
      system. After operation patients stay in hospital about 2-3 days, during this
      time they will receive information regarding how to take care of the
      wound,feeding and details about activities to avoid. Before patients leave
      hospital the nurse will confirm if parents can take care of patients wound,
      feeding, know about avoiding activities. The Nurses or health care professional
      can check patients progress again when they come back to hospital for follow-up.
      OBJECTIVE: To promote continuity care and resolve any problems for developing
      quality of care. MATERIAL AND METHOD: The present study is retrospective
      descriptive study. Data was collected from follow-up case forms using 205 medical
      records of patients with cleft lip and palate who were admitted in 3c ward
      Srinagarind Hospital between June 2010 to May 2011. The records were purposively
      selected for the study and recorded with a data collection form. RESULTS: 95.12%
      of patients with cleft lip and palate came back for follow-up. 2.44% of patients
      had wound infection. 7.69% of patients have flap separation. The authors also
      found that some care givers could not take care of the patients correctly and
      were not concerned about follow-up. CONCLUSION: To contracts the patients and
      family when they visit hospital for follow-up can make health care professional
      ensure the patients understand what they need to know and do, also can find any
      uncomfortable points/problem of patients/ family then can develop the strategies
      or system to solve the problem.

PMID- 23961631
TI  - Cerebral angiographic findings in patients with non-traumatic subarachnoid
      hemorrhage.
AB  - BACKGROUND: Even though ruptured intracranial aneurysm is a major cause of non
      traumatic subarachnoid hemorrhage (SAH), non-aneurysmal SAH has a good prognosis
      with few neurologic complications. The gold standard for detecting the vascular
      pathology is digital subtraction cerebral angiography (DSA). OBJECTIVE: The
      primary objective of the present study was to clarify cerebral angiographic
      findings in patients with non-traumatic subarachnoid hemorrhage (SAH); to define
      the incidence of nonaneurysmal SAH. The secondary aim was to review the clinical
      data of all of the patients diagnosed with non-traumatic SAH in order to
      determine the associated etiology. MATERIAL AND METHOD: This retrospective,
      descriptive study, was conducted at Srinagarind Hospital, Faculty of Medicine,
      Khon Kaen University, between January 2005 and November 2010. The authors
      reviewed the medical records, cranial computed tomography (CT) and DSA of
      patients with non-traumatic SAH. The DSA findings were assessed and the
      correlation with clinical data and CT pattern determined. RESULTS: The author
      included and analyzed the records of 118 non-traumatic SAH patients (66 females,
      52 males). The DSA discovered vascular lesions in 62.6% of cases (57.6% aneurysm,
      4.2% arteriovenous malformation (AVM) and 0.8% Moyamoya disease). A total of 76
      aneurysms were found in 68 cases. The location of the aneurysms included: 35.5%
      anterior communicating artery, 17.1% posterior communicating artery, 15.7% middle
      cerebral artery, 11.8% internal carotid artery 2.6% basilar artery, 1.3%
      vertebrobasillar junction and 10.5% others. The prevalence of nonaneurysmal SAH
      was 42.4% (50/118). In the multivariate analysis, hypertension was the factor
      most strongly associated with aneurysmal SAH on the DSA (p = 0.029). The location
      of SAH on Sylvian fissure was most frequently associated with the cause of
      aneurysms. In another way, tentorial cerebelli SAH was most commonly associated
      with a non-aneurysm cause. CONCLUSION: The present study revealed that the major
      cause of non-traumatic SAH is cerebral aneurysm. The factors associated with
      aneurysmal SAH included: hypertension and Sylvian fissure SAH. Tentorial
      cerebelli SAH was most commonly associated with a non-aneurysm cause.

PMID- 23961632
TI  - Frontal sinus drainage in Thai adult skulls.
AB  - OBJECTIVE: To study the pattern of the nasofrontal drainage in relation to the
      neighboring anatomical structures in adult Thai cadavers. MATERIAL AND METHOD:
      The anterior aspect of the frontal bone of the embalmed half-head was drilled to
      identify the presence of the frontal sinus i.e. 40 from only one side of each
      cadaver were chosen. A silicone base and catalyst were combined then injected
      into the frontal sinus, which flowed into the nasal cavity through its natural
      ostium, thereby creating a cast of the nasofrontal connection(s). After allowing
      five minutes for the silicone to set, the total vertical lamella of the middle
      turbinate was removed, so the cast could be measured, the connections
      meticulously dissected and the surrounding structures observed RESULTS: The
      investigation revealed five patterns of nasofrontal drainage. The most (60%)
      common pathway was directly through the frontal recess, while the other pathways
      12.5, 10, 10 and 7.5 percent were drained directly into the ethmoid infundibulum,
      through the agger nasi cell and then into the ethmoid infundibulum, into both the
      agger nasi cell, the ethmoid infundibulum and the suprabullar recess,
      respectively. The average sizes of the anteroposterior and mediolateral diameters
      of the frontal sinus ostium were 6.5 and 5.5 mm, respectively. The agger nasi
      cell was present in every cadaver with a frontal sinus and was always superior to
      the ventral attachment of the middle turbinate. CONCLUSION: The agger nasi cell
      is the key structure vis-a-vis planning and performing frontal sinus surgery. In
      preparation for endoscopic intranasal frontal sinus surgery, it is practical to
      extend the infundibulotomy superiorly into the agger nasi cell, then remove its
      medial, posterior and superior wall.

PMID- 23961633
TI  - The treatment of 4-5 year-old patients with cleft lip and cleft palate in
      Tawanchai Center: follow-up.
AB  - BACKGROUND: The highest incidence of cleft lip and cleft palate in Thailand
      occurs in the Northeast Region. Tawanchai Center was set up 10 years ago to be a
      specialized medical care center where an interdisciplinary team provides care for
      cleft lip and cleft palate patients. There has never previously been a study
      about 4-5 year old patients treated and followed-up by the multidisciplinary
      team. OBJECTIVE: To study the 4-5 year old patient's with cleft lip and cleft
      palate who received treatment and follow-up in Tawanchai Center, Srinagarind
      Hospital. MATERIAL AND METHOD: This retrospective study was conducted using data
      from every 4-5 years old cleft lip and cleft palate patients' medical record of
      the patients who had the continuous multidisciplinary treatment care at Tawanchai
      Center, Srinagarind Hospital, Faculty of Medicine and Faculty of Dentistry, Khon
      Kaen University. The 123 case samples were collected during the 3 months of April
      June 2012. The research instrument was a form for general data record and follow
      up data record and then the data were analyzed by statistic and percentage.
      RESULTS: From the 123 cases of the 4-5 years old patients with cleft lip and
      cleft palate who received treatment at Tawanchai Center Srinagarind Hospital, it
      was found that 120 cases or 97.56 percent had an operation, 20 cases (16.26
      percent) were found where patients came from Khon Kaen Province, 10 cases of each
      male and female. For this treatment, the majority (108 cases) used government
      insurance cards. The patients with cleft lip and cleft palate were most common
      and found to be 74 cases consisted of 44 male and 30 female. The diagnosis and
      follow-up of cleft lip and cleft palate patients were classified into 18 age
      ranges, with a total of 2,269 follow-up visits. The most common follow-up was for
      the 2-3 year old patients, which consisted of 410 times or 18.07 percent which
      consisted of 220 male and 190 female. Regarding the age range of the patients for
      the first diagnosis, the highest amount was 38 cases or 30.89 percent of 0-1
      month newborn which were 22 males and 16 females. Regarding examination rooms
      used, the highest number of patients attended the out-patient surgical
      examination room (969 times, 30.66 percent), of which 526 times were male and 443
      times female. The second highest number of patients attended the ENT room, 706
      times or 22.33 percent of which 411 times were male and 295 female. The 2
      patients with the highest number of follow-up were 87 and 65 times respectively.
      CONCLUSION: 123 cases of the 4-5 years patients had been continuously treated by
      the multidisciplinary team at Tawanchai Center Srinagarind Hospital. The highest
      number of visits was 87 or more than once per month, so it was a good opportunity
      for such a team to improve the efficiency and for developing the follow-up system
      and the diagnosis process for a baby with cleft lip and cleft palate before birth
      by use of ultrasound checking during pregnancy. Such a development was helpful
      for providing counseling towards mothers and families' preparation in order to
      give the most suitable age related treatment and full co-operative support to the
      children with cleft lip-cleft palate and family.

PMID- 23961634
TI  - Tawanchai Cleft Center quality of life outcomes: one of studies of patients with
      cleft lip and palate in Thailand and the Asia Pacific Region.
AB  - BACKGROUND: The needs and quality of life (QOL) of children with cleft lip and
      palate (CLP) after being processed through the healthcare system are important in
      order to understand how to improve the standards of care. The Tawanchai Cleft
      Center of Thailand in collaboration with Cleft Lip and Palate Care Center of the
      Asia Pacific Region, conducted a number of studies on various aspects of
      treatment outcomes as an indication of its performance. This paper presents the
      outcome effects on QOL. OBJECTIVE: To determine (a) the QOL of children with CLP
      in Northeast Thailand registered and followed-up at the Tawanchai Centre, (b)
      their ongoing care needs and (c) the mental health of their parents when the
      children reach 5 years of age. MATERIAL AND METHOD: Using the Need, Satisfaction,
      QOL and GHQ-12 questionnaires, the authors evaluated 36 five-year-old children
      with CLP, living in Northeast Thailand, registered at birth for treatment at the
      Tawanchai Cleft Center. RESULTS: The aspects most needing attention were: dental,
      speech therapy and local healthcare service. The QOL was low in the economic,
      child relationships and psychological domains. The parents need more training on
      how to raise children with CLP most appropriately. According to the GHQ-12, none
      of the families identified any mental problems. CONCLUSION: Children with CLP at
      five years of age under the care of the Tawanchai Cleft Center by their own self
      assessment have satisfactory outcomes in most domains. Notwithstanding, there is
      need to improve parent training and access to dental care, speech therapy and
      local healthcare services.

PMID- 23961635
TI  - Medical care for 4- to 5-year-olds with cleft lip/palate at the Tawanchai Center:
      geoinformatics study.
AB  - BACKGROUND: The incidence of cleft lip and cleft palate in Thailand is based on
      reports from three hospitals in Northeastern Thailand. There are 2.49 new babies
      born with cleft lip and cleft palate and craniofacial deformities for every 1,000
      babies the highest incidence in the world. Area 7 Office of the National Health
      Security Office (NHSO) comprises Khon Kaen, Roi Et, Mahasarakam and Kalasin. The
      number of newborns with cleft lip and palate is an estimated 114 cases/year. A
      retrospective geoinformatics study was conducted using the medical records of 4-
      to 5-year-olds with cleft lip and cleft palate registered with the Tawanchai
      Center Srinagarind Hospital. OBJECTIVE: To study the distribution of 4- to 5-year
      olds with cleft lip and palate using geoinformatics. MATERIAL AND METHOD: This
      retrospective study was conducted using data from the medical records, which
      contains the records of 4- to 5-year-olds with cleft lip and cleft palate
      admitted to Srinagarind Hospital. The 54-patient sample groups were registered at
      the Tawanchai Center Faculty of Medicine, Khon Kaen University, under the aegis
      of the NHSO (Area 7-Khon Kaen). The data were collected using self-administered
      questionnaires between May and June 2012 and geoinformatics, to study the
      distribution of patients' vis-a-vis the various parameters. RESULTS: Among the 27
      male and 27femalepatients, 51.85% had cleft lip with cleft palate. Most of the
      cleft lip patients (7 cases; 41.18%) were in Khon Kaen, while 4 (44.44%) of the
      cleft palate patients were in Roi-Et and 11 (39.29%) of the cleft lip with palate
      patients were in Khon Kaen. Most cleft lip patients were in Roi-Et province: 1
      case in each of four districts. Similarly, most cases of cleft palate were in Roi
      Et province: 1 case in each of four districts. Finally, most cases (5; 50%) of
      cleft lip with cleft palate were found in Roi-Et province, mostly in the central
      (Muang) district. CONCLUSION: The use of Arc View software as an instrument for
      geoinformatics, spatial data collection helped to clarify the district level
      distribution of patients with CLP; this information is needed for policy planning
      and resource allocation.

PMID- 23961636
TI  - Landmark of ethmoid arteries in adult Thai cadavers: application for sinus
      surgery.
AB  - BACKGROUND: Ethmoid arteries, branches of the ophthalmic artery, are crucial
      structures supplying ethmoid mucosa. Its locations are important during ethmoid
      sinus surgery. There has been no study in Thais before. OBJECTIVE: To determine
      the number and locations of ethmoid arteries in relation to important surrounding
      structures. MATERIAL AND METHOD: A prospective, descriptive study in 42 Thai
      cadaveric adult half-heads was conducted at departments of Otorhinolaryngology
      and Anatomy, Faculty of Medicine, Khon Kaen University, Thailand. Meticulous
      dissections were performed to identify number of ethmoid arteries branching from
      ophthalmic artery and site of entrance of the arteries into ethmoid sinus.
      Relationships of these arteries with anterior ethmoid crest, optic foramen, bulla
      lamella and middle third of basal lamella of middle turbinate were studied.
      OUTCOMES: Types of ethmoid arteries, distances between ethmoid arteries and their
      relations to important surrounding structures: anterior lacrimal crest, optic
      foramen, superior aspects of bulla lamella, middle third of basal lamella of
      middle turbinate and the superior aspect of anterior wall of sphenoid sinus.
      RESULTS: All specimens had anterior and posterior ethmoid arteries. The
      prevalence of tertiary ethmoid artery was 36% (95% CI22-52%). The mean distance
      between the anterior ethmoid artery and anterior lacrimal crest, anterior ethmoid
      artery and posterior ethmoid artery and the distance between posterior ethmoid
      artery and optic foramen were 24.3, 13.5 and 6.4 millimeters respectively. Most
      of the entry of anterior ethmoid artery into the ethmoid sinus was in the
      posterior half of the distance between the bulla lamella and middle third of
      basal lamella of middle turbinate, 85.7%. CONCLUSION: This is the first study of
      location of ethmoid arteries in Thai adult cadavers. The information of the
      present study may be useful for sinus surgeon.

PMID- 23961637
TI  - Development of community based model of Tawanchai Center: sufficiency economy
      principles for community Development an applicability at Bankhambong Community,
      Sa-ard Sub-district, Nampong District, Khon Kaen Province, Thailand.
AB  - The objectives of the present study are 1) to study the application of
      sufficiency economy philosophy in community development as a model for future
      application of community health care program of Tawanchai Center, 2) study the
      administrative model for self sufficiency economy community in Bankhambong
      Community, Sa-ard Sub-district, Nampong District, Khon Kaen Province. The
      integrated study model included qualitative research by collecting data from
      documents, textbook, article, report, theory concept, researches and interviewing
      of relevant persons and the quantitative research by collecting data from
      questionnaires. The findings of study included objectives for development model
      of sufficiency economy for understanding of people, and use the philosophy of
      sufficiency economy model which compose of decrease expenditure, increase income
      activities, saving activities, learning activities and preservation of
      environment and sustainable natural resources activities. Decrease in expenditure
      activities included household gardening, and no allurements leading to ruin.
      Increase in income activities included supplement occupation and appropriate use
      of technology. Saving activities included creating saving group in household and
      community level. Learning activities included community use of local wisdom, and
      household learnt philosophy of sufficiency economy in daily living. Preservation
      of environment and sustainable natural resources activities included the use of
      sustainable raw materials in occupation. The generosity of one another activities
      included helping each other and solving problems for the poor and disable
      persons. The community development at in Bankhambong Community, Sa-ard Sub
      district, Nampong District, Khon Kaen Province followed all of the above scope
      and guidelines and is the model for application of sufficiency community
      philosophy. We recommended method for successful implementation, including the
      starting from group process with capability of learning to create strong and
      adequate knowledge to apply sufficiency economy model and cover health care.

PMID- 23961638
TI  - Modified bilateral neurovascular cheek flaps: a new technique for reconstruction
      of difficult and extensive lower lip defect.
AB  - The reconstruction of the extensive lip defects after surgical resection of
      tumors is challenging. Various methods have been used for reconstruction of these
      defects, however, the ideal functional reconstruction of these lip defects are
      difficult to achieve. The author describes a modified bilateral neurovascular
      flaps technique which provide a satisfactory cosmetic appearance and good
      functional results.

PMID- 23961639
TI  - Two-hole trephination (Muntarbhorn) technique for a large frontal sinus osteoma:
      a case report.
AB  - OBJECTIVE: To present an alternative surgical option for frontal sinus osteoma.
      MATERIAL AND METHOD: A woman presented with a symptomatic large osteoma in right
      frontal sinus. Two-hole trephination was planned to remove the osteoma using
      nasal endoscope and a drill in each hole. RESULTS: The osteoma was drilled and
      removed transnasally. Two months later, two small fragments of osteoma were
      detected remaining in the lateral aspect of the sinus. The fragments were removed
      successfully with the same technique. The patient was asymptomatic six months
      postoperatively. CONCLUSION: Two-hole trephination technique or Muntarbhorn
      technique is an attractive option for frontal sinus osteoma.

PMID- 23961640
TI  - Surgery first orthognathic approach for skeletal Class III malocclusion
      corrections--a literature review.
AB  - Management for patients with skeletal Class III malocclusion is orthognathic
      surgery which involves both orthodontics and surgery. Nowadays, there are two
      approaches for orthognathic surgery: orthodontics-first and surgery-first
      approaches. The orthodontics-first approach, or presurgical orthodontics
      treatment, causes longer treatment time and worsens facial appearance before
      surgery compared with a surgery-first approach. Conversely, with the surgery
      first approach or the surgery-first-orthognathic-approach (SFOA), correction can
      be resolved more rapidly. SFOA needs high level skill of orthodontist and surgeon
      and also needs good cooperation between them to accomplish best results. The
      purpose of this article is to review the concept, indications, contraindications,
      the stages of treatment and advantages, and disadvantages of SFOA.

PMID- 23961642
TI  - [Still far too many persons become infected also in Germany with HIV (interview
      by Peter Leiner)].

PMID- 23961641
TI  - [HIV positive for years: now weight loss and nodules on the face. Disseminated
      histoplasmosis].

PMID- 23961643
TI  - [Therapy of hepatitis C: new inhibitors as hammers against HCV].

PMID- 23961644
TI  - [AIDS: no longer a fatal epidemic].

PMID- 23961645
TI  - [History of 25 years antiretroviral therapy].

PMID- 23961646
TI  - [History of the "Berlin patient" and the promise of a zinc-finger based HIV gene
      therapy].

PMID- 23961647
TI  - [ First integrase inhibitor based single tablet regimen].

PMID- 23961648
TI  - [Revolutionizing HIV-therapy by Tre-Recombinase? Initial observations and current
      state of development].

PMID- 23961649
TI  - [The concept of the new ERA study].

PMID- 23961650
TI  - [The skin is itching: is HIV the cause?].

PMID- 23961651
TI  - [Raltegravir - long lasting effectiveness, well tolerated and well combined].

PMID- 23961652
TI  - [Better prognosis: when and which screening methods and immunizations in HIV
      infected people].

PMID- 23961653
TI  - [Development of a vaccine against HIV: is this aim accomplishable?].

PMID- 23961654
TI  - [Striving for individual therapy].

PMID- 23961655
TI  - [Interview with Dr. med. Nazifa Qurishi, Koln, and with Siegfried Schwarze,
      Berlin. HIV therapy from the viewpoint of a physician and of a patient].

PMID- 23961656
TI  - [PrEP approved in the USA: facts and discussion - permanent chemoprophylaxis for
      healthy people].

PMID- 23961657
TI  - [Mechanism of bone destruction in rheumatoid arthritis].

PMID- 23961658
TI  - [Paradigm shift and future perspectives in rheumatoid arthritis].
AB  - Introduction of methotrexate (MTX) and biologic agents caused a paradigm shift in
      the treatment of rheumatoid arthritis(RA). Development of new classification
      criteria for RA was established in 2010, which makes early diagnosis of RA
      possible. Treating to target (T2T) by setting treatment goal avoids irreversible
      joint damage and disability in RA. Remission, thus became a realistic goal with
      early diagnosis and intervention. Consequently, not only clinical but also
      structural and functional remission can be achieved with the current treatment.
      However, risk managements with the use of these agents are also of importance. In
      addition, there remains unmet needs in RA treatment.

PMID- 23961659
TI  - [Pathological mechanisms in rheumatoid arthritis].
AB  - Rheumatoid arthritis(RA) is a representative autoimmune disease characterized by
      systemic, chronic, destructive inflammatory synovitis and multiple organ
      manifestations, resulting in severe disability and mortality rates. Immune cells
      such as T cells, B cells, dendritic cells and macrophages and cellular
      interaction among them through cytokines and cell surface molecules plays a
      pivotal role in the pathological processes of RA. The accumulation of
      inflammatory cells, the self-perpetuation of inflammation and induction and/or
      activation of osteoclasts lead to cartilage and bone destruction and multiple
      organ manifestations. The importance of immune systems in the pathogenesis of RA
      has become apparent based on the clinical efficacy of biologic agents TNF, IL-6,
      CD28 and CD20. The research translation between bench and bedside would bring
      enormous progress in the treatment of RA.

PMID- 23961660
TI  - [Genetic analyses of rheumatoid arthritis].
AB  - The etiology of rheumatoid arthritis (RA) is unknown and genetic information is
      important for understanding the mechanisms of the disorder. In order to identify
      diseases-associated genes, genome wide association study (GWAS) has been
      performed. Through GWAS, many RA associated genes have been reported. Several
      genes are related to T cell differentiation, signaling in the immune cells,
      innate immunity and TNF signaling. Some of these polymorphisms are shared by
      several autoimmune diseases. On the other hands, it is important to know that
      there are ethnic differences in these autoimmune related genes. We reported
      functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine
      deiminase 4, are associated with RA. We also identified an RA associated
      polymorphism in the promoter region of FCRL3, a member of the Fc receptor-like
      family. Through these studies, we believe that we could obtain further insights
      into the disease mechanisms, develop novel therapies and make personalized
      medicine possible based on the individual's genetics.

PMID- 23961661
TI  - [An important aspect of the 2010 American College of Rheumatology/European League
      Against Rheumatism classification criteria for the diagnosis of rheumatoid
      arthritis].
AB  - Remission has become a realistic goal in the management of rheumatoid
      arthritis(RA). The 2010 American College of Rheumatology/European League Against
      Rheumatism (ACR/EULAR) classification criteria focus on early-stage RA, and were
      specifically designed to address the deficiencies in the 1987 criteria, primarily
      a lack of sensitivity. However, these criteria are not intended for diagnosis in
      routine clinical care. RA should be suspected in the patient who presents with
      inflammatory polyarthritis. Initial evaluation of such patients requires a
      careful history and physical examination, along with select laboratory testing to
      identify features that are characteristic of RA or that suggest an alternative
      diagnosis. Radiographs should also be performed. Further research will eventually
      lead to more reliable diagnostic and classification criteria for new-onset RA.

PMID- 23961662
TI  - [Pharmacological management of rheumatoid arthritis: the state of the art and the
      future perspective].
AB  - Pharmacological management of rheumatoid arthritis (RA) has been rapidly
      progressed in recent years, which is appeared in the "treat to target" movement
      and the recommendations developed by some established international/domestic
      rheumatology associations. The baseline evaluation of poor prognostic factors as
      well as disease activity with composite measures is necessary for a personalized
      management. Methotrexate is currently the anchor drug, and other conventional or
      biological antirheumatic drugs should be added to it for refractory patients. The
      development of various novel agents including signal transduction inhibitors
      should promote further advances in the management of RA and other systemic
      autoimmune and/or inflammatory diseases.

PMID- 23961663
TI  - [A focus on the diagnosis of early rheumatoid arthritis].
AB  - The need for early initiation of treatment in rheumatoid arthritis (RA) has been
      established. The 1987 RA classification criteria are not suitable for this
      strategy. Therefore, as a collaboration of ACR and EULAR, new classification
      criteria for RA were published in 2010. Several studies assessed agreement
      between 1987 and 2010 criteria and the potential source of discordance. This
      review will describe the current evidence evaluating the 2010 criteria, and show
      some important questions regarding the criteria.

PMID- 23961664
TI  - [Hematologic, biochemical, and immunological tests in clinical practice of
      rheumatoid arthritis].
AB  - In clinical practice of rheumatoid arthritis (RA), various kinds of laboratory
      tests are required for diagnosis, assessment of the disease activity, assessment
      of complications and risk factors before starting therapy, and assessment of
      adverse effects during the therapy. Anemia, thrombocytosis, and leukocytosis are
      common in active RA. During RA therapies, liver function tests (including ALT and
      AST) and renal function tests (including serum creatinine and urinalysis) should
      be performed. Anti-CCP antibody is an especially useful marker for diagnosis of
      RA, and the presence of the antibody has been included in ACR/EULAR 2010 RA
      classification criteria. Reactivation of hepatitis B virus (HBV) after
      immunosuppressive therapies is a potentially serious complication. HBc and/or HBs
      antibodies should be measured before starting the therapies even if HBs antigen
      is negative, and appropriate interventions including measurement of HBV-DNA and
      starting prophylaxis (entecavir is recommended) should be performed.

PMID- 23961665
TI  - [Evaluation of joint damage with conventional radiograph and synovitis with
      musculoskeletal ultrasonography in rheumatoid arthritis].
AB  - Conventional radiograph has been and still is the gold standard measure to
      evaluate the joint damage of rheumatoid arthritis (RA), visualizing the features
      characteristic to RA such as bone erosion and joint space narrowing. The Larsen
      grade is utilized in the evaluation of large joints, whereas the Sharp score and
      its modified versions are commonly used in clinical trials to quantify the joint
      damage progression. Ultrasound, on the other hand, can visualize both synovial
      inflammation and the subsequent structural damage, which shifted the paradigm of
      imaging in RA. Our data indicate that the evaluation of synovial inflammation
      with ultrasound improves the accuracy of diagnosis and disease activity
      assessment of RA.

PMID- 23961666
TI  - [Imaging of rheumatoid arthritis: role of MR imaging and CT].
AB  - An increasing aggressive therapeutic strategy has attracted growing attention to
      the potentials of MR imaging in the diagnosis, prognostication, and outcome
      measure of rheumatoid arthritis (RA). In the diagnosis of RA, skeletal
      destructions are the key to the diagnosis and assessment of long-term prognosis
      in RA. Marginal bone erosion is still recognized as an important finding in the
      2010 RA criteria, and erosions typical of RA are deemed to have prima facie
      evidence of RA. MR imaging can detect erosions better than radiolography. In this
      regard, erosions detected by CT are considered to be reference standard to
      evaluate diagnostic accuracy of erosion in MR imaging and other imaging
      modalities. Further, to assess therapeutic effect of therapeutic agents involving
      the control of bone remodeling, CT may be used to evaluate bone formation and
      improvement of osteoporosis.

PMID- 23961667
TI  - [DMARDs (disease-modifying antirheumatic drugs)].
AB  - Disease-modifying antirheumatic drugs (DMARDs) have largely contributed to recent
      paradigm shift of rheumatoid arthritis (RA) treatment strategy. DMARDs can be
      indicated for all RA patients and early use of DMARDs after diagnosis of RA is
      recommended. Individual DMARDs have common characteristics. Understanding these
      characteristics is very important in treating RA. As for safety, the pattern of
      adverse reactions (ADRs) associated with DMARDs has been generally understood. It
      is necessary to select DMARDs and follow up patients with recognition of the
      pattern of ADRs. Regular monitoring is also essential to ensure the safety of
      DMARDs. This chapter deals with some major DMARDs in Japan, including
      methotrexate, which is indispensable in current RA treatment; salazosulfapyridine
      and bucillamine; tacrolimus, which is recently increasing in use; and iguratimod,
      which became available in 2012.

PMID- 23961668
TI  - [Efficacy and adverse reactions of the TNFalpha inhibitor infliximab in
      rheumatoid arthritis].
AB  - Abundant evidence of infliximab (tumor necrosis factor inhibitor) has been
      collected in rheumatoid arthritis. Infliximab is effective not only for resolving
      the clinical symptoms, but also for preventing joint destruction. It has also
      been reported that discontinuation of this drug is possible after attaining low
      disease activity. This is one of the characteristics of infliximab. However,
      patients should be adequately cautioned against the development of adverse
      reactions, such as infections. It is essential to carefully select patients
      eligible for treatment with infliximab based on the guidelines established by the
      Japan College of Rheumatology, and adverse reactions to the drug should be
      prevented or detected early and treated promptly.

PMID- 23961669
TI  - [Etanercept].
AB  - Etanercept (ETN) is a fusion protein of the receptor (CD120b) for tumor necrosis
      factor (TNF) and the Fc portion of IgG1. A phase III trail and the JESMR study,
      both performed in Japan, implicated the importance of concomitant methotrexate
      (MTX) use in the treatment of rheumatoid arthritis (RA). Further evidences,
      including the TEAR study and the PRESERVE study, supported the recent treatment
      strategy for RA, being divided into at least two phases: remission induction
      phase(step-up or initial combination) and its maintenance phase (step-down).
      Thus, optimization of RA treatment chiefly based on MTX and anti-TNF biological
      agents is in progress.

PMID- 23961670
TI  - [Adalimumab].
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by
      inflammation of the synovial joints, and eventual destruction of cartilage and
      bone, as well as various extra-articular signs and symptoms. The TNF-alpha
      blocker adalimumab (ADA) is a fully human IgG1 monoclonal antibody that
      neutralizes both soluble and membrane-bound TNF in humans. Several clinical
      trials have provided compelling evidence of the safety and clinical efficacy of
      ADA for both the induction and maintenance of remission in RA. Moreover, the
      beneficial effects of ADA on bone destruction seen in the joint of RA have been
      demonstrated by recent clinical investigation. This review will discuss the
      clinical efficacy and utility of ADA in the management of RA.

PMID- 23961671
TI  - [Golimumab].
AB  - Golimumab is one of the TNF-inhibitors, having an efficacy and safety profile
      comparable to other TNF-inhibitors. In addition, golimumab is a fully human
      monoclonal antibody, has several unique features, such as neutralizing antibodies
      are difficult to generate. In clinical trials carried out in Japan, the efficacy
      and safety of administration of golimumab 100 mg every 4 weeks is shown, and
      golimumab blood concentration related to efficacy have been pointed out. From
      these, golimumab is considered a useful drug in every step of the treatment of
      rheumatoid arthritis. This section reviews the clinical trials of golimumab, and
      consider the useful use of golimumab.

PMID- 23961672
TI  - [Abatacept].
AB  - Rheumatoid arthritis (RA) is an autoimmune disease that targets synovial joints
      and leads to bone destruction and joint deformity. T cell activations were shown
      to be involved in the onset of RA. T cells may control downstream inflammatory
      mediators reaching the synovium, where inflammation leads to joint destruction.
      However the treatment of RA has improved considerably in recent years through the
      introduction of DMARDs such as MTX, and anti-tumor necrosis factor therapy, there
      is still unmet medical need. Not a few patients experience an inadequate response
      to these therapies. Abatacept, a fusion protein of the extracellular domain of
      CTLA4 (a molecule inhibits the costimulatory pathway in T cell activation) and
      the Fc domain of human IgG1, was developed for the treatment of RA. Abatacept has
      shown long-term efficacy and safety in RA patients who were inadequate to MTX
      and/or anti-tumor necrosis factor therapy.

PMID- 23961673
TI  - [Tocilizumab].
AB  - IL-6 plays a pivotal role in the pathogenesis of RA. Tocilizumab (TCZ) is a
      humanized monoclonal antibody to IL-6 receptor, and is now the only biological
      agent targeting IL-6. The main indication of TCZ for RA patients is those who has
      been resistant to DMARDs including MTX. TCZ may be also effective for anti-TNF
      therapy resistant RA. In addition, TCZ can be used effectively as monotherapy.
      The following screening tests for opportunistic infections should be done before
      starting TCZ; chest X-ray and tuberculin test or interferon-gamma releasing assay
      for detecting latent tuberculosis, HBs antigen and HBc antibody for detecting HBV
      carrier, beta-D-glucan for screening fungal and pneumocystis infection, etc.
      After starting TCZ, we should be careful for symptoms and signs of infections and
      allergic reactions, and monitor white blood cell count, liver funtion test and
      serum lipds.

PMID- 23961674
TI  - [JAK inhibitor].
AB  - Biologics targeting inflammatory cytokine has become a standardized tool for
      remission induction in rheumatoid arthritis (RA). However, it is handled under
      restricted conditions and their cost of acquisition is high. Small molecule drugs
      targeting Janus kinase (JAK), a molecule involved in intracellular signaling
      pathway has shown similar treatment effect as biologics. Moreover, inhibitory
      effect on bone destruction has been demonstrated and has been approved in 2012 as
      a new disease modifying anti-rheumatic drug in USA. However, since the inhibition
      of JAK results in inhibition of multiple cytokine signaling pathways, the
      clinical studies have also shown adverse events differing from biologics.

PMID- 23961675
TI  - [Syk inhibitors].
AB  - Non-receptor type of protein-tyrosine kinase Syk (spleen tyrosine kinase) was
      isolated in the University of Fukui in 1991. Syk is known to be essential for the
      various physiological functions, especially in hematopoietic lineage cells.
      Moreover, ectopic expression of Syk by epigenetic changes is reported to cause
      retinoblastoma. Recently, novel Syk inhibitors were developed and its usefulness
      has been evaluated in the treatment of allergic rhinitis, rheumatoid arthritis,
      and idiopathic thrombocytopenic purpura. In this review, we will summarize the
      history, structure, and function of Syk, and then describe the novel Syk
      inhibitors and their current status. Furthermore, we will introduce our findings
      of the adaptor protein 3BP2 (c-Abl SH3 domain-binding protein-2), as a novel
      target of Syk.

PMID- 23961676
TI  - [Anti-cytokine treatment, newly developed].
AB  - Rheumatoid arthritis (RA) is characterized by chronic inflammatory synovitis that
      causes pain, loss of function and disability, and can significantly reduce health
      related quality of life. Improved understanding of the pathogenesis has led to
      the development of new biologic treatments that target specific cytokines. Large
      randomized controlled trials (RCTs) have been conducted to show the efficacy of
      anti-TNF and IL-6. However, despite these treatments, some patients fail to
      respond to these therapies. Recently other anti-ctyokine treatments had been
      developed and introduced. Here, we discuss about new anti-cytokine treatments for
      RA.

PMID- 23961677
TI  - [Glucocorticoids].
AB  - The established evidence of the rapid effects, along with the growing recognition
      of their disease-modifying properties has led us to reconsider the potential of
      glucocorticoids in the treatment of rheumatoid arthritis. Given their acceptable
      safety profile, especially when used at low dosages, several glucocorticoid-based
      therapeutic approaches have been explored in order to optimize their clinical
      benefits, while limiting the adverse effects. Encouraging results on the clinical
      and sub-clinical effects of low dosages are going to lead to a shift in usual
      daily practice. Optimizing the use of key non-biologic drugs including
      glucocorticoids may prolong disease control, thereby delaying the need for costly
      biologic therapies.

PMID- 23961678
TI  - [Arthroscopic synovectomy for rheumatoid arthritis].
AB  - Even though the paradigm shift was occurred in treatments for rheumatoid
      arthritis (RA), some patients are not well controlled with several treatments.
      Because arthroscopic techniques advanced remarkably, effectiveness of
      arthroscopic synovectomy is reconsidered, especially for residual synovitis in
      biologics unresponders. A combined therapy with biologics and arthroscopic
      synovectomy leads to improvement of composite measures such as DAS28.
      Arthroscopic synovectomy can be a powerful tool for the tight control in RA
      treatments. In addition with progressions of ultrasonography, ultrasound-guided
      regional anesthesia became popular recently. Using this technique, we can expand
      indication of surgical intervention even in patients with severe lung problems.

PMID- 23961679
TI  - [Total joint arthroplasty].
AB  - Control of the disease activity is enabled due to the progress of drug therapy
      for rheumatoid arthritis. However, surgical treatments are necessary for
      unresponsive cases to the drug or for achieving higher QOL, and we can attain
      more tight control or cure by combination of drug therapy and surgical
      treatments. Total joint arthroplasty provides indolence, mobility, stability and
      is an useful joint reconstruction method. Shoulder and elbow joint work as a
      reach function together, and total joint arthroplasty become adaptation when
      extensive joint destruction or severe pain occurrs. With the usage of biologic
      agents joint repair is possible in small joints, but if the joint destruction
      progress in weight-bearing joints, repair is impossible and total joint
      arthroplasty can be required.

PMID- 23961680
TI  - [Surgical reconstruction of joint function].
AB  - In recent years a concept of "treat to target" is introduced into a medical
      treatment of RA, and tight control is recommended from the early stage of the
      disease. However, it is difficult to relieve all patients in a true remission.
      Nowadays, disease activity is controlled well and a reconstructive surgery is
      performed at a limited number of the damaged joints in a state of good remaining
      of bone and soft tissue structures. The patients are highly motivated, and a
      newly developed disorder at the non-surgically treated joints is uncommon.
      Therefore, an aggressive rehabilitation is possible. Combined with a medical
      treatment of RA, a surgical intervention enables to acquire a higher level of ADL
      and an improved QOL (Japanese T2T).

PMID- 23961681
TI  - [Rehabilitation therapy according to the disease condition and functional status
      of the patients with rheumatoid arthritis].
AB  - Rehabilitation for the patients with rheumatoid arthritis(RA), such as exercise
      therapy, application of splints and patient education, has contributed to the
      improvement in both impairments and disabilities due to the dysfunction of
      locomotive systems. Recent progress in drug therapy has influenced the
      rehabilitation approach toward the RA, because an effective pain management by
      itself facilitates ease of movement and improves the deteriorated locomotive
      functions. Early initiation of exercise therapy is reported to prevent a
      reduction in grip power under the conventional drug-therapy. Moreover, it is also
      reported that the exercise in addition to the biologics have shown better effects
      in the functional recovery of upper extremities in comparison with the regimen of
      biologics alone. While many patients have benefited from the recent advances in
      drug therapy, several patients still suffer impairments and disabilities without
      benefits of biologics due to long disease durations before biologics treatment,
      adverse effects of drugs and financial problems. The suggestions by EULAR, 'treat
      to target (T2T)' proposed that the goal of RA treatment should be to maximize
      long-term health-related quality of life through control of symptoms, prevention
      of structural damage, normalization of function and social participation. This is
      in the same way of rehabilitation. Though the objectives and methods of
      rehabilitation vary for individual patients, it should be appropriately
      prescribed for every individual patient based on evaluation of the patients'
      disabilities in order to enhance their QOL as well as ADL.

PMID- 23961682
TI  - [Social security system for patients with rheumatoid arthritis in Japan].
AB  - Support system for patients with rheumatoid arthritis (RA) is a wide variety,
      such as the health care, the medical economy, the environment, and mental
      activity. Among these measures, the laws called the social security system are
      defined. These systems consist of social insurance (medical insurance, long-term
      care insurance, pension insurance), social welfare (welfare for the disabled) and
      public health (measures for intractable diseases). As social support under total
      management of RA, patients can receive mitigation measures and subsidies
      (physically disabled person's certificate, high-cost medical care, etc.) for high
      medical expenses at use of biological products, hospitalization and surgery.
      Furthermore long-term care insurance and disability pension can be used as a
      further support of home care.

PMID- 23961683
TI  - [Post-ischemic innate immunity and its application for novel therapeutic strategy
      targeting brain inflammation].
AB  - Stroke or brain ischemia is one of the major causes of death and disability
      worldwide. Post-ischemic inflammation is an essential step in the progression of
      brain ischemia-reperfusion injury. In a mouse stroke model, we have reported that
      IL-23 produced from infiltrating macrophages induces IL-17 producing T cells. IL
      17 is mainly produced from gammadeltaT cells and promotes delayed (day 3-4)
      ischemic brain damage. We also demonstrated that peroxiredoxin (Prx) family
      proteins released extracellularly from necrotic brain cells induce expression of
      inflammatory cytokines including IL-23 in macrophages through activation of Toll
      like receptor 2(TLR2) and TLR4, thereby promoting neural cell death. We thus
      propose that regulation of the IL-23-IL-17 axis including gammadeltaT cells,
      macrophages, and extracellular Prxs could be a potent neuroprotective tool.

PMID- 23961684
TI  - [Strategy of liver resection during chemotherapy for otherwise unresectable
      colorectal metastases].
AB  - With multidisciplinary management of patients with effective chemotherapy that
      can downstage metastases, more patients with previously inoperable disease can
      benefit from surgery. Surgery in isolation may be approaching technical limits,
      but now is likely to help more patients because of success of complementary
      strategies, particularly newer chemotherapy and targeted therapy. Leaving behind
      disappearing metastases after chemotherapy, margin-positive resection, staged
      liver resection, and liver-first reversed management permit potentially curative
      surgery for patients previously unable to survive resection. Further, survival
      benefit from maximum debulking surgery, like ovarian cancer, for colorectal liver
      metastases is uncertain at present, but likely. Individualized multidisciplinary
      treatment planning using such strategies is essential.

PMID- 23961685
TI  - On implementation of an endodontic program.
AB  - It is widely accepted that the uptake of research findings by practitioners is
      unpredictable, yet until they are adopted, advances in technology and clinical
      research cannot improve health outcomes in patients. Despite extensive research
      there is limited knowledge of the processes by which changes occur and ways of
      measuring the effectiveness of change of practice. The overall aim of this thesis
      was to investigate aspects of an educational intervention in clinical endodontic
      routines and new instrumentation techniques in a Swedish County Public Dental
      Service. Special reference was made to the establishment of changed behaviour in
      practice, the process of change, and the clinical effects. Although a high level
      of competence in root canal treatment procedures is required in general dental
      practice, a number of Swedish studies have revealed inadequate root-fillings
      quality and associated periapical inflammation in general populations. It is
      suggested that the adoption of the nickel-titanium rotary instrumentation (NiTiR)
      technique would improve the cleaning and shaping of root canals and the quality
      of the root-filling. However, there is limited knowledge of the effectiveness of
      the technique when applied in general dental practice. In two of four consecutive
      studies, the subjects were employees of a county Public Dental Service. The aim
      was to investigate the rate of adoption of clinical routines and the NiTiR
      technique: the output, and the qualitative meaning of successful change in
      clinical practice. In the other two studies the aim was to investigate treatment
      effect and the cost-effectiveness of root canal treatment in a general
      population: the outcome. Four hundred employees (dentists, dental assistants,
      administrative assistants and clinical managers) of a Swedish County Public
      Dental Service were mandatorily enrolled in an educational and training program
      over two years. Change of practice was investigated in a post-education survey.
      The NiTiR technique was adopted by significantly more dentists in the
      intervention county compared to a control county (77% and 6% respectively).
      Dentists in the intervention county completed root canal instrumentation in
      significantly fewer sessions than the dentists in the control county. Eight in
      depth interviews, two with each participant, (dentist, dental assistant,
      receptionist, clinical manager), were strategically selected for a
      phenomenological analysis. Four factors were identified as necessary for
      successful change: 1) disclosed motivation, 2) allowance for individual learning
      processes, 3) continuous professional collaboration, and 4) a facilitating
      educator. A random sample of 850 performed root canal treatments was used for a
      study of treatment outcome; 425 before and 425 after the education and adoption
      of the NiTiR technique. Root-filling quality, periapical status and tooth
      survival were assessed on radiographs taken at treatment and at follow-up, > or =
      4 years later. Apical periodontitis was found in 34% of the teeth root-filled
      before the education compared to 33%, after. After the education, root-filling
      quality improved significantly, tooth survival was significantly higher, however,
      without a subsequent improvement in success rate post-education; 68% vs. 67%. A
      micro-costing model was used to calculate the costs of root canal
      instrumentation, pre- and post-education, in the same sample used in the study of
      treatment outcome. Costs were lower post-education: by SEK 264 for teeth with one
      canal and SEK 564 for teeth with three or more canals. A reason for lower costs
      was that the NiTiR technique dominated after the education and required
      significantly fewer instrumentation sessions. A cost-minimization analysis
      disclosed that root canal treatments undertaken post-education were more cost
      effective. In conclusion, there was only a partial relationship between output
      and outcome. Although root-filling quality improved significantly, the study did
      not show any association between the more frequent use of NiTiR and an
      improvement in remaining teeth with normal periapical status or success rate.
      However, the use of NiTiR was more cost-effective. These results are in
      accordance with previous findings of the so called efficacy-effectiveness gap in
      clinical practice: a high output is not predictive of a high outcome. The overall
      conclusion to be drawn from these studies is that further research is warranted
      to identify factors associated with improvement of the quality of endodontic
      care. The general interpretation of the findings of these implementation studies
      is as important as the effects of the change in endodontic instrumentation: a
      clinically relevant and applicable intervention, introduced by experienced
      expertise under allowing learning and collaborating circumstances, disclosed
      clinicians' motivation and facilitated implementation. The finding of qualitative
      differences between the questionnaire responses and the in-depth interviews
      suggest that a critical approach is warranted when comparing surveys and
      qualitative methods aimed at investigating qualitative experiences of change, due
      to their different epistemological premises.

PMID- 23961686
TI  - Managing uncertainty in the academy and the courtroom: normal arsenic and
      nineteenth-century toxicology.
AB  - This essay explores how the enhanced sensitivity of chemical tests sometimes
      produced unforeseen and puzzling problems in nineteenth-century toxicology. It
      focuses on the earliest uses of the Marsh test for arsenic and the controversy
      surrounding "normal arsenic"--that is, the existence of traces of arsenic in
      healthy human bodies. The essay follows the circulation of the Marsh test in
      French toxicology and its appearance in the academy, the laboratory, and the
      courtroom. The new chemical tests could detect very small quantities of poison,
      but their high sensitivity also offered new opportunities for imaginative defense
      attorneys to undermine the credibility of expert witnesses. In this context,
      toxicologists had to dispel the uncertainty associated with the new method and
      come up with arguments to refute the many possible criticisms of their findings,
      among them the appeal to normal arsenic. Meanwhile, new descriptions of animal
      experiments, autopsies, and cases of poisoning produced a steady flow of
      empirical data, sometimes supporting but in many cases questioning previous
      conclusions about the reliability of the chemical tests. This challenging
      scenario provides many clues about the complex interaction between science and
      the law in the nineteenth century, particularly how expert authority,
      credibility, and trustworthiness were constructed, and frequently challenged, in
      the courtroom.

PMID- 23961687
TI  - The in/visible women: Mariangela Ardinghelli and the circulation of knowledge
      between Paris and Naples in the eighteenth century.
AB  - Mariangela Ardinghelli (1730-1825) is remembered as the Italian translator of two
      texts by the Newtonian physiologist Stephen Hales, Haemastaticks and Vegetable
      Staticks. This essay shows that her role in the Republic of Letters was by no
      means limited to such work. At a time of increasing interest in the natural
      history of the areas around Naples, she became a reliable cultural mediator for
      French travelers and naturalists. She also acted as an informal foreign
      correspondent for the Paris Academy of Sciences, connecting scientific
      communities in Naples and France. Unlike other learned women of the time,
      Ardinghelli was neither an aristocrat nor a member of the ascendant middle class.
      The essay discusses the strategies she devised to build her authority and her
      choice of anonymity at the apex of her popularity, when she translated scientific
      texts by contemporary celebrities such as the abbe Nollet and the comte de
      Buffon. It argues that, in spite of Ardinghelli's historical invisibility, for
      her contemporaries she never became an "invisible assistant": she constructed
      layers of selective visibility that allowed her authorship to be identified by
      specific audiences, while protecting herself from social isolation or derision.

PMID- 23961688
TI  - Botanical smuts and hermaphrodites: Lydia Becker, Darwin's botany, and education
      reform.
AB  - In 1868, Lydia Becker (1827-1890), the renowned Manchester suffragist, announced
      in a talk before the British Association for the Advancement of Science that the
      mind had no sex. A year later, she presented original botanical research at the
      BAAS, contending that a parasitic fungus forced normally single-sex female
      flowers of Lychnis diurna to develop stamens and become hermaphroditic. This
      essay uncovers the complex relationship between Lydia Becker's botanical research
      and her stance on women's rights by investigating how her interest in
      evolutionary theory, as well as her correspondence with Charles Darwin,
      critically informed her reform agendas by providing her with a new vocabulary for
      advocating for equality. One of the facts that Becker took away from her work on
      Lychnis was that even supposedly fixed, dichotomous categories such as biological
      sex became unfocused under the evolutionary lens. The details of evolutionary
      theory, from specific arguments on structural adaptations to more encompassing
      theories on heredity (i.e., pangenesis), informed Becker's understanding of human
      physiology. At the same time, Becker's belief in the fundamental equality of the
      sexes enabled her to perceive the distinction between inherent, biological
      differences and culturally contingent ones. She applied biological principles to
      social constructs as she asked: Do analogous evolutionary forces act on humans?

PMID- 23961689
TI  - A natural history of mathematics: George Peacock and the making of English
      algebra.
AB  - In a series of papers read to the Cambridge Philosophical Society through the
      1820s, the Cambridge mathematician George Peacock laid the foundation for a
      natural history of arithmetic that would tell a story of human progress from
      counting to modern arithmetic. The trajectory of that history, Peacock argued,
      established algebraic analysis as a form of universal reasoning that used
      empirically warranted operations of mind to think with symbols on paper. The
      science of counting would suggest arithmetic, arithmetic would suggest
      arithmetical algebra, and, finally, arithmetical algebra would suggest symbolic
      algebra. This philosophy of suggestion provided the foundation for Peacock's
      "principle of equivalent forms," which justified the practice of nineteenth
      century English symbolic algebra. Peacock's philosophy of suggestion owed a
      considerable debt to the early Cambridge Philosophical Society culture of natural
      history. The aim of this essay is to show how that culture of natural history was
      constitutively significant to the practice of nineteenth-century English algebra.

PMID- 23961690
TI  - Insect control in socialist China and the corporate United States: the act of
      comparison, the tendency to forget, and the construction of difference in 1970s
      U.S.-Chinese scientific exchange.
AB  - In 1975, a delegation of U.S. entomologists traveled to socialist China to
      observe Chinese insect control science. Their overwhelmingly positive reports
      highlighted in relief the pernicious effects of pesticide corporations on U.S.
      agriculture; some entomologists hoped this would goad the United States to catch
      up to China in environmentally sensible insect control practices. Of course,
      insect control in socialist China carried its own political baggage, some of
      which-for example, mass mobilization and self-reliance--the state made highly
      visible to visitors, and some of which--for example, harsh treatment of
      scientists--it sought to obscure. For both the U.S. and the Chinese participants,
      the act of comparison itself was of primary significance in the exchange,
      allowing them to construct socialist Chinese science as refreshingly different
      from U.S. science. At the same time, however, this construction of difference
      meant forgetting the much longer transnational history in which U.S. and Chinese
      entomology had been intertwined.

PMID- 23961691
TI  - Focus: science, history, and modern India. Introduction.
AB  - Histories of science in India are revisitations of the colonial question. Science
      is ideology to be unraveled and exposed--as modernity and progress making or
      violence and oppression making--depending on where you stand on the interpretive
      spectrum. It has been seen as ideologically driven practice, as a mode of
      knowledge production whose history is inseparable from the social and political
      uses to which it is tethered. In the colonial as well as the postcolonial
      context, science and technology have been seen as the "ideology of empire,"
      "tools of empire," "tentacles of progress," and "reasons of state." Yet science
      and technology are practices and bodies of knowledge that inhabitants of the
      subcontinent have engaged with enthusiasm, that they have used to invent
      themselves in their global, national, and individual lives. We know remarkably
      little about the histories of these complex engagements. A departure from current
      historiographical preoccupations is called for to map and explain the lives,
      institutions, practices, and stories of science on the subcontinent as they
      connect with, and where they break away from, the world at large.

PMID- 23961692
TI  - Beyond postcolonialism ... and postpositivism: circulation and the global history
      of science.
AB  - This essay traces the parallel, but unrelated, evolution of two sets of reactions
      to traditional idealist history of science in a world-historical context. While
      the scholars who fostered the postcolonial approach, in dealing with modern
      science in the non-West, espoused an idealist vision, they nevertheless stressed
      its political and ideological underpinnings and engaged with the question of its
      putative Western roots. The postidealist history of science developed its own
      vision with respect to the question of the global spread of modern science,
      paying little heed to postcolonial debates. It then proposes a historiographical
      approach developed in large part by historians of South Asian politics,
      economics, and science that, without compromising the preoccupations of each of
      the two groups, could help construct a mutually comprehensible and connected
      framework for the understanding of the global workings of the sciences.

PMID- 23961693
TI  - Well-ordered science and Indian epistemic cultures: toward a polycentered history
      of science.
AB  - This essay defends the view that "modern science," as with modernity in general,
      is a polycentered phenomenon, something that appears in different forms at
      different times and places. It begins with two ideas about the nature of rational
      scientific inquiry: Karin Knorr Cetina's idea of "epistemic cultures," and Philip
      Kitcher's idea of science as "a system of public knowledge," such knowledge as
      would be deemed worthwhile by an ideal conversation among the whole public under
      conditions of mutual engagement. This account of the nature of scientific
      practice provides us with a new perspective from which to understand key elements
      in the philosophical project of Jaina logicians in the seventh, eighth, and ninth
      centuries C.E. Jaina theory seems exceptionally well targeted onto two of the key
      constituents in the ideal conversation--the classification of all human points of
      view and the representation of end states of the deliberative process. The
      Buddhist theory of the Kathavatthu contributes to Indian epistemic culture in a
      different way: by supplying a detailed theory of how human dialogical standpoints
      can be revised in the ideal conversation, an account of the phenomenon Kitcher
      labels "tutoring." Thus science in India has its own history, one that should be
      studied in comparison and contrast with the history of science in Europe. In
      answer to Joseph Needham, it was not 'modern science' which failed to develop in
      India or China but rather non-well-ordered science, science as unconstrained by
      social value and democratic consent. What I argue is that this is not a deficit
      in the civilisational histories of these countries, but a virtue.

PMID- 23961694
TI  - Nehruvian science and postcolonial India.
AB  - This essay uses the seminal figure of Jawaharlal Nehru to interrogate the nature
      and representation of science in modern India. The problem posed by Nehruvian
      science--the conflict between (yet simultaneity of) science as both universal
      phenomenon and local effect--lies at the heart of current debates about what
      science means for the non-West. The problematic of Nehruvian science can be
      accessed through Nehru's own speeches and writings, but also through the wider
      project of science with which he identified--critiquing colonialism, forging
      India's place in the modern world, marrying intellectual endeavor with practical
      nation building. The essay makes a case for looking at Nehruvian science as a way
      of structuring the problem of postcolonial science, particularly in relation to
      understanding the authority of science and its evaluation in terms of its
      capacity to deliver socioeconomic change.

PMID- 23961695
TI  - A historian among scientists: reflections on archiving the history of science in
      postcolonial India.
AB  - How might we overcome the lack of archival resources while doing the history of
      science in India? Offering reflections on the nature of archival resources that
      could be collected for scientific institutions and the need for new
      interpretative tools with which to understand these resources, this essay argues
      for the use of oral history in order to understand the practices of science in
      the postcolonial context. The oral history of science can become a tool with
      which to understand the hidden interactions between the world of scientific
      institutions and the larger world of the postcolonial nation.

PMID- 23961696
TI  - The scholastic impetus theory: interpretations of modern scholars.

PMID- 23961698
TI  - Molecularly imprinted polymer microspheres containing photoswitchable spiropyran
      based binding sites.
AB  - A versatile approach for the preparation of photoswitchable molecularly imprinted
      polymers (MIPs) is proposed where the selective recognition and the
      photoresponsive function are assumed by two different monomers. As a proof of
      concept, MIP microspheres were synthesized by precipitation polymerization for
      recognizing terbutylazine, a triazine-type herbicide. Formation of the selective
      binding sites was based upon H-bonding interactions between the template and the
      functional monomer methacrylic acid, whereas a polymerizable spiropyran unit was
      incorporated into the polymer matrix to provide light-controllable
      characteristics. A trifunctional monomer, trimethylolpropane trimethacrylate, was
      used as a cross-linker. The imprinted particles exhibited considerable
      morphological differences compared to their nonimprinted counterparts as observed
      by scanning electron microscopy. The imprinting effect was confirmed by
      equilibrium rebinding studies. The photoresponsiveness of the polymer particles
      was visualized by fluorescence microscopy and further characterized by
      spectroscopy. The template binding behavior could be regulated by alternating UV
      and visible light illumination when analyte release and uptake was observed,
      respectively. Binding isotherms fitted by the Freundlich model revealed the
      photomodulation of the number of binding sites and their average affinity. This
      facile synthetic approach may give an attractive starting point to endow
      currently existing highly selective MIPs with photoswitchable properties, thereby
      extending the scope of spiropyran-based photoresponsive smart materials. 

PMID- 23961697
TI  - Induction of 8,5'-cyclo-2'-deoxyadenosine and 8,5'-cyclo-2'-deoxyguanosine in
      isolated DNA by Fenton-type reagents.
AB  - Exposure of aqueous solutions of DNA to X- or gamma-rays, which induces the
      hydroxyl radical as one of the major reactive oxygen species (ROS), can result in
      the generation of a battery of single-nucleobase and bulky DNA lesions. These
      include the (5'R) and (5'S) diastereomers of 8,5'-cyclo-2'-deoxyadenosine (cdA)
      and 8,5'-cyclo-2'-deoxyguanosine (cdG), which were also found to be present at
      appreciable levels in DNA isolated from mammalian cells and tissues. However, it
      remains unexplored how efficiently the cdA and cdG can be induced by Fenton-type
      reagents. By employing HPLC coupled with tandem mass spectrometry (LC-MS/MS/MS)
      with the use of the isotope-dilution technique, here we demonstrated that
      treatment of calf thymus DNA with Cu(II) or Fe(II), together with H2O2 and
      ascorbate, could lead to dose-responsive formation of both the (5'R) and (5'S)
      diastereomers of cdA and cdG, though the yields of cdG were 2-4 orders of
      magnitude lower than that of 8-oxo-7,8-dihydro-2'-deoxyguanosine. This result
      suggests that the Fenton reaction may constitute an important endogenous source
      for the formation of the cdA and cdG. Additionally, the (5'R) diastereomers of
      cdA and cdG were induced at markedly higher levels than the (5'S) counterparts.
      This latter finding, in conjunction with the previous observations of similar or
      greater levels of the (5'S) than (5'R) diastereomers of the two lesions in
      mammalian tissues, furnishes an additional line of evidence to support the more
      efficient repair of the (5'R) diastereomers of the purine cyclonucleosides in
      mammalian cells. 

PMID- 23961699
TI  - Axial-site modifications of paddlewheel diruthenium(II, II) complexes supported
      by hydrogen bonding.
AB  - The reactions of paddlewheel-type diruthenium(II, II) complexes, [Ru2(II,II)(x
      FPhCO2)4(THF)2] (x-FPhCO2(-) = x-fluorobenzoate with x- = o-, m-, p-), with 2,6
      diaminopyridine (dapy) and 7-azaindole (azain) afford axially capped discrete
      compounds, [Ru2(II,II)(x-FPhCO2)4(dapy)2] (x = o-, 1; m-, 2; p-, 3) and
      [Ru2(II,II)(o-FPhCO2)4(azain)2] (4), respectively. In these compounds,
      intramolecular hydrogen bonds are observed between NH2 groups for 1-3 or imine NH
      groups for 4 and oxygen atoms of carboxylate groups. In addition, hydrogen bonds
      of NH2...F are also observed for 1 and 4 with an o-positioned F atom on benzoate.
      This coordination mode, i.e., a dual bonding mode with sigma-bonding and hydrogen
      bonding, should assist ligand coordination to the axial position of the [Ru2]
      unit. The Ru-N bond distance in 1-4 is shorter than that observed in related
      compounds reported previously. In a similar fashion, reactions with planar M(II)
      dithiobiuret (dtb) complexes, [M(II)(dtb)2] (M(II) = Pd(II) and Pt(II)), were
      carried out. One-dimensional alternating chains, [{Ru2(II,II)(o
      FPhCO2)4}{M(II)(dtb)2}] (M(II) = Pd(II), 5; Pt(II), 6), were obtained, in which
      the hydrogen-bonding modes of NH2...O and NH2...F are present, as expected. DFT
      calculations for the [M(II)(dtb)2] unit revealed that the LUMO of [M(II)(dtb)2]
      lies at -2.159 and -1.781 eV for M = Pd and Pt, respectively, which is much
      higher than HOMO energy at -4.184 eV calculated for [Ru2(II,II)(o-FPhCO2)(THF)2],
      proving that the respective units are essentially electronically isolated in the
      chains. 

PMID- 23961700
TI  - pH effects on the molecular structure of beta-lactoglobulin modified air-water
      interfaces and its impact on foam rheology.
AB  - Macroscopic properties of aqueous beta-lactoglobulin (BLG) foams and the
      molecular properties of BLG modified air-water interfaces as their major
      structural element were investigated with a unique combination of foam rheology
      measurements and interfacial sensitive methods such as sum-frequency generation
      and interfacial dilatational rheology. The molecular structure and protein
      protein interactions at the air-water interface can be changed substantially with
      the solution pH and result in major changes in interfacial dilational and foam
      rheology. At a pH near the interfacial isoelectric point BLG molecules carry zero
      net charge and disordered multilayers with the highest interfacial dilatational
      elasticity are formed at the air-water interface. Increasing or decreasing the pH
      with respect to the isoelectric point leads to the formation of a BLG monolayer
      with repulsive electrostatic interactions among the adsorbed molecules which
      decrease the interfacial dilational elasticity. The latter molecular information
      does explain the behavior of BLG foams in our rheological studies, where in fact
      the highest apparent yield stresses and storage moduli are established with foams
      from electrolyte solutions with a pH close to the isoelectric point of BLG. At
      this pH the gas bubbles of the foam are stabilized by BLG multilayers with
      attractive intermolecular interactions at the ubiquitous air-water interfaces,
      while BLG layers with repulsive interactions decrease the apparent yield stress
      and storage moduli as stabilization of gas bubbles with a monolayer of BLG is
      less effective. 

PMID- 23961702
TI  - The effect of strenuous and exhaustive exercise on learning.
AB  - In view of reported effects of strenuous and exhaustive exercise on CNS activity,
      it was hypothesized that "fatiguing" exercise may influence learning
      retroactively as predicted by consolidation theory. Prelimary findings from two
      animal experiments are reported followed by a discussion of implications for
      future research. 

PMID- 23961703
TI  - Temporary fatigue effects in a gross motor skill.
AB  - 75 male college Ss were randomly assigned to one of three treatment groups to
      investigate the comparative effects of initial and initial-plus-interpolated
      total-body physical fatigue upon learning and performance of a gross motor skill.
      Each S was tested on the Mirror Target Toss Test before and after the appropriate
      experimental condition allotted to his group: initial, initial-plus-interpolated,
      and rest. The data were transformed into learning scores by the percent of
      possible improvement method and analyzed by a simple analysis of variance.
      Despite substantial effects on the performance curves, neither initial nor
      interpolated fatigue had any permanent effect on the acquisition of skill. 

PMID- 23961701
TI  - A mixed methods multiple case study of implementation as usual in children's
      social service organizations: study protocol.
AB  - BACKGROUND: Improving quality in children's mental health and social service
      settings will require implementation strategies capable of moving effective
      treatments and other innovations (e.g., assessment tools) into routine care. It
      is likely that efforts to identify, develop, and refine implementation strategies
      will be more successful if they are informed by relevant stakeholders and are
      responsive to the strengths and limitations of the contexts and implementation
      processes identified in usual care settings. This study will describe: the types
      of implementation strategies used; how organizational leaders make decisions
      about what to implement and how to approach the implementation process;
      organizational stakeholders' perceptions of different implementation strategies;
      and the potential influence of organizational culture and climate on
      implementation strategy selection, implementation decision-making, and
      stakeholders' perceptions of implementation strategies. METHODS/DESIGN: This
      study is a mixed methods multiple case study of seven children's social service
      organizations in one Midwestern city in the United States that compose the
      control group of a larger randomized controlled trial. Qualitative data will
      include semi-structured interviews with organizational leaders (e.g.,
      CEOs/directors, clinical directors, program managers) and a review of documents
      (e.g., implementation and quality improvement plans, program manuals, etc.) that
      will shed light on implementation decision-making and specific implementation
      strategies that are used to implement new programs and practices. Additionally,
      focus groups with clinicians will explore their perceptions of a range of
      implementation strategies. This qualitative work will inform the development of a
      Web-based survey that will assess the perceived effectiveness, relative
      importance, acceptability, feasibility, and appropriateness of implementation
      strategies from the perspective of both clinicians and organizational leaders.
      Finally, the Organizational Social Context measure will be used to assess
      organizational culture and climate. Qualitative, quantitative, and mixed methods
      data will be analyzed and interpreted at the case level as well as across cases
      in order to highlight meaningful similarities, differences, and site-specific
      experiences. DISCUSSION: This study is designed to inform efforts to develop more
      effective implementation strategies by fully describing the implementation
      experiences of a sample of community-based organizations that provide mental
      health services to youth in one Midwestern city.

PMID- 23961704
TI  - Transfer of work decrement in motor learning.
AB  - Two experiments tested the hypothesis that the decremental effects of massed
      practice are due to the development of a negative drive (Hull's Ir). The results
      indicated that the decremental effects of massed practice on either the pursuit
      rotor or the two-hand coordinator do not transfer to depress performance or
      reminiscence on the other task. The results did not support Hull's drive
      interpretation but were explained by theories attributing decrement to a
      decreased level of arousal. 

PMID- 23961705
TI  - Performance criteria for stabilometer learning.
AB  - A method for collecting multiple dependent variables (DVs) on stabilometer
      performance is described. The relative sensitivity of 6 measures of stabilometer
      performance was determined within a 2 * 2 * 2 * 6 (blocks of 5 trials) factorial
      design. Two levels each of Plane of Balance, KR, and Starting Position were
      independent variables. Ss (N=80) performed 30 trials with a 30-sec. intertrial
      rest. Univariate ANOVA revealed significant changes across blocks on four of the
      six DVs measured. Multivariate ANOVA of the three treatment effects revealed KR
      significant, p<.01. Discriminant function analysis indicated a measure of S's
      variability about a chosen balance point as the best discriminator for the KR
      factor. Recording continuous analog information of S's response revealed the
      stabilometer sensitive to S's learning. Results were discussed in terms of the
      role of KR, task criterion manipulations, and the use of the stabilometer as a
      motor task within theoretical frameworks. 

PMID- 23961706
TI  - Bilateral reminiscence in inverted-reversed printing.
AB  - Reported is a study of bilateral reminiscence in printing inverted-reversed
      alphabetic letters. Independent variables were the printing-Hand Sequence (left
      to-right vs. right-to-left), and the Interpolated Activity (control vs. upright
      reading vs. inverted reading). These variables were factorially combined in a 2 *
      3 design with 30 Ss per cell. On second-hand performance, the upright groups were
      found to be superior to the combined inverted and control groups under both
      sequence conditions. However, the inverted group was superior to the control
      group only in the left-to-right condition and not in the right-to-left condition.
      This latter result was discussed as possibly being due to the specialization of
      the cerebral hemispheres for certain types of processing activities. Implications
      of this hypothesis were pointed out for further research, and for possible
      mechanisms producing reactive inhibition in the central nervous system. 

PMID- 23961707
TI  - Latency and response complexity.
AB  - Two experiments were conducted in which the latency of movement responses of
      varying complexity was investigated. The complexity of an arm sweep movement was
      varied by (a) increasing the extent of movement from 6 in. to 18 in., (b)
      reversing the movement, and (c) by making two or three pauses in an on-going
      movement. The results only partially supported the hypothesis that the latency of
      a response is related to the complexity of the movement pattern. Specifically RT
      was longer when the response involved significant changes in the temporal
      organization of the movement pattern. 

PMID- 23961708
TI  - Effects of classically differentiated supplementary feedback cues on tracking
      skill.
AB  - Although previous studies had shown that classical predifferentiation of green
      (CS-j and red (CS+) cues enabled them to facilitate tracking performance when
      used as supplementary indicators of correct and incorrect responses respectively,
      the studies were inconclusive concerning specific conditional properties versus
      nonspecific arousal consequences of the cues. A sample of 108 Ss was exposed to
      the same predifferentiation procedure, but then were subgrouped in terms of the
      kind of feedback signal received in tracking (no signal, red only, green only,
      both signals). A nonspecificity theory predicts subgroup equality of tracking
      performances while specificity theory predicts the dependence of performance
      level on the kind of signal received. Results corroborated previous findings and
      the view that tracking effects were reasonably attributable to the transfer of
      specific stimulus functions generated in the differentiation trials. 

PMID- 23961709
TI  - Effector organization and "gradation" of effort.
AB  - It is proposed that an aspect of the effector organization process is the
      gradation of the response. Gradation was investigated in a hand cranking task by
      using strain-gauge and electromyographic recording techniques. Criteria of
      gradation were related to (a) the impulsive force at a particular point in the
      cycle of movement, (b) an index of the work done per unit of time, (c) the degree
      of muscle activity in each of the 6 muscles analyzed, and (d) an index of muscle
      activity based on the pen deflection of an EMG record. Further, two criteria of
      the organization of the force were employed - the force range and the consistency
      of the force range. None of the criteria of gradation was closely related to
      speed of performance, but the organizational criteria showed a trend toward being
      related to speed. The implications of these findings are discussed. 

PMID- 23961711
TI  - Histologic changes in the adrenal gland reflect fetal distress in hydrops
      fetalis.
AB  - The distribution of lipid in the fetal adrenal cortex is reported to correlate
      with the duration of hypoxia and degree of fetal stress. The original studies
      were based on Oil Red O staining, requiring frozen tissue that is often not
      available. To investigate the reliability of these observations, the distribution
      of lipid in the fetal adrenal cortex was studied in hydrops fetalis (HF) of
      different etiologies, using immunostaining for adipophilin on formalin-fixed
      material. Twenty cases of HF due to hemoglobin (Hb) Bart were compared to 34
      cases of HF due to other causes. In the fetal zone, lipid distribution was more
      diffuse in Hb Bart HF compared to other causes of HF, including those due to
      anemia, supporting the concept that increased lipid in the fetal zone is
      associated with severity of hypoxia. A more diffuse distribution of lipid
      correlated with adrenal cytomegaly (P < 0.01) and extramedullary hematopoiesis (P
      < 0.01) but not Hb level (P  =  0.68) nor compact cell change (P  =  0.7) or
      cystic degeneration (P  =  0.07) in the definitive zone. A greater degree of
      cystic degeneration correlated with lower gestational age, rather than the
      specific etiology of HF. Thus, cystic degeneration is more a reflection of the
      onset of fetal stress than severity. The combined histologic changes in the fetal
      and definitive zones of the adrenal gland provide complementary information about
      fetal status in HF. Immnunostaining for adipophilin circumvents the need for
      frozen tissue for assessing lipid content by Oil Red O staining, facilitating
      studies based on archival material.

PMID- 23961710
TI  - Global expression profiling reveals genetic programs underlying the developmental
      divergence between mouse and human embryogenesis.
AB  - BACKGROUND: Mouse has served as an excellent model for studying human development
      and diseases due to its similarity to human. Advances in transgenic and knockout
      studies in mouse have dramatically strengthened the use of this model and
      significantly improved our understanding of gene function during development in
      the past few decades. More recently, global gene expression analyses have
      revealed novel features in early embryogenesis up to gastrulation stages and have
      indeed provided molecular evidence supporting the conservation in early
      development in human and mouse. On the other hand, little information is known
      about the gene regulatory networks governing the subsequent organogenesis.
      Importantly, mouse and human development diverges during organogenesis. For
      instance, the mouse embryo is born around the end of organogenesis while in human
      the subsequent fetal period of ongoing growth and maturation of most organs spans
      more than 2/3 of human embryogenesis. While two recent studies reported the gene
      expression profiles during human organogenesis, no global gene expression
      analysis had been done for mouse organogenesis. RESULTS: Here we report a
      detailed analysis of the global gene expression profiles from egg to the end of
      organogenesis in mouse. Our studies have revealed distinct temporal regulation
      patterns for genes belonging to different functional (Gene Ontology or GO)
      categories that support their roles during organogenesis. More importantly,
      comparative analyses identify both conserved and divergent gene regulation
      programs in mouse and human organogenesis, with the latter likely responsible for
      the developmental divergence between the two species, and further suggest a novel
      developmental strategy during vertebrate evolution. CONCLUSIONS: We have reported
      here the first genome-wide gene expression analysis of the entire mouse
      embryogenesis and compared the transcriptome atlas during mouse and human
      embryogenesis. Given our earlier observation that genes function in a given
      process tends to be developmentally co-regulated during organogenesis, our
      microarray data here should help to identify genes associated with mouse
      development and/or infer the developmental functions of unknown genes. In
      addition, our study might be useful for invesgtigating the molecular basis of
      vertebrate evolution.

PMID- 23961713
TI  - A new pentacyclic triterpenoid from the leaves of Lantana montevidensis (Spreng.)
      Briq.
AB  - A new pentacyclic triterpenoid, 3beta,25-epoxy-3alpha,22beta,23alpha-trihydroxy
      olean-12-en-28-oic acid (1), together with seven known compounds, including five
      triterpenoids, beta-amyrin (2), lantadene B (3), lantanilic acid (4), lantanolic
      acid (5) and ursolic acid (6) in addition to beta-sitosterol (7) and benzoic acid
      (8) has been isolated from the leaves of Lantana montevidensis. Their chemical
      structures were elucidated by spectroscopic analysis and by comparison with the
      literature data and/or authentic samples. Compound 1 showed moderate to weak
      antibacterial activity against Staphylococcus aureus and Escherichia coli. 

PMID- 23961712
TI  - Chronotype and breast cancer risk in a cohort of US nurses.
AB  - The aim of this study was to examine the relation between chronotype and breast
      cancer risk. We analyzed the association between chronotype (definite morning
      type, probable morning type, probable evening type, definite evening type, or
      neither morning nor evening type) and breast cancer risk among 72 517 women in
      the Nurses' Health Study II (NHS II). Chronotype was self-reported in 2009, and
      1834 breast cancer cases were confirmed among participants between 1989 and 2007;
      a 2-yr lag period was imposed to account for possible circadian disruptions
      related to breast cancer diagnosis. Age- and multivariable-adjusted logistic
      regression was used to estimate odds ratios (ORs) and 95% confidence intervals
      (CIs). Participants who self-reported as neither morning nor evening type had a
      27% increased risk of breast cancer (multivariable-adjusted OR = 1.27, 95% CI =
      1.04-1.56), compared with definite morning types. None of the other chronotypes
      were significantly associated with breast cancer risk (multivariable-adjusted OR
      = 0.99, 95% CI = 0.87-1.12 for probable morning versus definite morning types; OR
      = 0.96, 95% CI = 0.84-1.09 for probable evening versus definite morning types;
      and OR = 1.15, 95% CI = 0.98-1.34 for definite evening versus definite morning
      types). Overall, chronotype was not associated with breast cancer risk in our
      study. A modestly increased risk among neither morning nor evening types may
      indicate circadian disruption as a potentially underlying mechanism; however,
      more studies are needed to confirm our results. 

PMID- 23961714
TI  - Facile one-pot assembly of imidazotriazolobenzodiazepines via indium(III)
      catalyzed multicomponent reactions.
AB  - An operationally simple, one-pot multicomponent reaction has been developed for
      the assembly of 9H-benzo[f]imidazo[1,2-d][1,2,3]triazolo[1,5-a][1,4]diazepines
      adorned with three diversification points via an atom-economical transformation
      incorporating alpha-diketones, o-azidobenzaldehydes, propargylic amines, and
      ammonium acetate. This process involves tandem InCl3-catalyzed cyclocondensation
      and intramolecular azide-alkyne 1,3-dipolar cycloaddition reactions; optimization
      data, substrate scope, and mechanistic insights are discussed. 

PMID- 23961715
TI  - Prognostic role of plasma von Willebrand factor and soluble E-selectin levels for
      future cardiovascular events in a 'real-world' community cohort of patients with
      atrial fibrillation.
AB  - BACKGROUND: Endothelial damage/dysfunction may contribute to a prothrombotic
      state in patients with atrial fibrillation (AF) and the increased risk of
      thromboembolism and cardiovascular events. Raised plasma von Willebrand factor
      (vWf), an established marker of endothelial damage/dysfunction, has been
      associated with stroke and vascular events, at least in a clinical trial
      population. Soluble E-selectin (sE-sel) is another biomarker of endothelial
      activation/dysfunction, with more limited data on prognostic outcomes in AF.
      OBJECTIVE: To assess the relationship between the levels of vWf, sE-sel and
      clinical adverse outcomes (including stroke, MI and all-cause mortality) in a
      'real-world' community cohort of patients with AF. METHODS: We studied 423
      patients (mean age 72.7 +/- 8.4 years, 55.6% male) with nonvalvular AF, with a
      median follow-up of 19 (9-31) months. Plasma vWf and sE-sel levels were measured
      using enzyme-linked immunosorbent assay (ELISA). RESULTS: There were 94 clinical
      adverse events (22.2%) observed during a median follow-up of 19 months. Patients
      with clinical events had significantly higher vWf (P < 0.001) and sE-sel levels
      at baseline (P < 0.001) compared with those who were event free. Kaplan-Meir
      analyses demonstrated that more clinical adverse events occurred in the upper
      tertile of vWf [upper vs. lowest tertile, RR 3.8, 95% CI (2.63-5.57), P < 0.001;
      upper vs. middle tertile, RR 10.5, 95% CI (5.33-20.60), P < 0.001]. Similarly,
      the highest tertile of sE-sel was associated with more adverse events [upper vs.
      lowest tertile, RR 3.7, 95% CI (2.51-5.31), P < 0.001; upper vs. middle tertile,
      RR 6.5, 95% CI (3.56-11.91), P < 0.001]. CONCLUSION: High plasma vWf and soluble
      E-selectin levels are associated with an increased risk of clinical adverse
      events (acute myocardial infarction, ischaemic stroke and all-cause mortality) in
      'real-world' patients with AF. These soluble biomarkers may potentially aid
      clinical risk stratification in this common arrhythmia.

PMID- 23961716
TI  - The effect of simvastatin on lipid droplets accumulation in human embryonic
      kidney cells and pancreatic cancer cells.
AB  - BACKGROUND: Statins (HMG-CoA reductase inhibitors) represent a major class of
      compounds for the treatment of hypercholesterolemia due to their ability to
      inhibit de novo cholesterol synthesis. In addition to their hypolipidemic
      effects, chemoprotective properties have been attributed to statins as well.
      These effects involve multiple mechanisms, which, however, are not known in
      detail. The aim of our study was to assess in non-malignant as well as cancer
      cells the impact of simvastatin on the amount of cytosolic lipid droplets (LDs)
      implicated in many biological processes including proliferation, inflammation,
      carcinogenesis, apoptosis, necrosis or growth arrest. METHODS: Human embryonic
      kidney cells HEK-293T and human pancreatic cancer cells MiaPaCa-2 were treated
      with simvastatin (6 and 12 MUM) for 24 and 48 hours respectively. Neutral lipid
      probe Nile Red was used for detection of LDs by fluorescence microscopy. Cellular
      cholesterol content was determined by HPLC. Changes in expression of genes
      related to lipid metabolism in simvastatin-treated MiaPaCa-2 cells were examined
      by DNA microarray analysis. Validation of gene expression changes was performed
      using quantitative RT-PCR. RESULTS: The treatment of the cells with simvastatin
      increased their intracellular content of LDs in both non-malignant as well as
      cancer cells, partially due to the uptake of cholesterol and triacylglyceroles
      from medium; but in particular, due to enhanced synthesis of triacylglyceroles as
      proved by significant overexpression of genes related to de novo synthesis of
      triacylglyceroles and phospholipids. In addition, simvastatin also markedly
      influenced expression of genes directly affecting cell proliferation and
      signaling. CONCLUSIONS: Simvastatin treatment led to accumulation of cytosolic
      LDs within the examined cells, a phenomenon which might contribute to the
      antiproliferative effects of statins.

PMID- 23961717
TI  - Discontinued drugs in 2012: endocrine and metabolic.
AB  - INTRODUCTION: This perspective summarizes 42 drug projects in the general areas
      of endocrine and metabolic diseases that were reported discontinued during 2012.
      AREAS COVERED: These programs include development projects against diabetes,
      metabolic complications (including kidney and liver disease), as well as projects
      that can be described as approaches to treatment of obesity/anorexia, lipids and
      various inflammatory diseases. Candidates were identified from a search by
      Informa Healthcare including data available on TreasureTrove as provided by EOID.
      Additional information was sought using Google, PubMed, HighWire and
      ClinicalTrials.gov. EXPERT OPINION: The summary of discontinued projects in this
      area for 2012 provides little in the way of specific guidance especially since
      details of the fate of most projects are often lacking. Nonetheless, it seems
      clear that none of these projects has hit upon the key aspects of the
      pathophysiology of the disorders that they were intended to treat, and the most
      likely cause of failure is the lack of the ability to produce compelling evidence
      to support the respective business case in the sense of efficacy/potential
      therapeutic profile.

PMID- 23961718
TI  - Correction: Functional disruption of macrophage migration inhibitory factor (MIF)
      suppresses proliferation of human h460 lung cancer cells by caspase-dependent
      apoptosis.

PMID- 23961720
TI  - Allostery and folding of the N-terminal receiver domain of protein NtrC.
AB  - The N-terminal receiver domain of protein NtrC (NtrC(r)) exhibits allosteric
      transitions between the inactive (unphosphorylated) and active (phosphorylated)
      state on the microsecond time scale. Using a coarse-grained variational model
      with coupled energy basins, we illustrate that significant loss of conformational
      flexibility is the key determinant of the inactive (I) -> active (A) state
      transition mechanism of NtrC(r). In particular, our results reveal that the
      rearrangements of the native contacts involving the regulatory helix-alpha4 and
      the flexible beta3-alpha3 loop upon activation play a crucial role in the
      activation mechanism. Interestingly, we find that the beta3-alpha3 loop exhibits
      a gradual decrease in flexibility throughout the activation transition, while
      helix-alpha4, in contrast, becomes more rigid abruptly near the free energy
      barrier separating the two states. To gain further insight into role these
      flexible regions play in the transition mechanism, we consider folding of NtrC(r)
      to both states using a similar model. Our calculated folding routes suggest that
      helix-alpha4 becomes structured later when folding to the I state compared to
      folding of the A state, a result consistent with it is relative conformational
      flexibility in the two states. Finally, we find a good qualitative agreement
      between our predicted I -> A transition mechanism and the measured backbone
      dynamics from nuclear magnetic resonance experiments. 

PMID- 23961719
TI  - Incremental value of rare genetic variants for the prediction of multifactorial
      diseases.
AB  - BACKGROUND: It is often assumed that rare genetic variants will improve available
      risk prediction scores. We aimed to estimate the added predictive ability of rare
      variants for risk prediction of common diseases in hypothetical scenarios.
      METHODS: In simulated data, we constructed risk models with an area under the ROC
      curve (AUC) ranging between 0.50 and 0.95, to which we added a single variant
      representing the cumulative frequency and effect (odds ratio, OR) of multiple
      rare variants. The frequency of the rare variant ranged between 0.0001 and 0.01
      and the OR between 2 and 10. We assessed the resulting AUC, increment in AUC,
      integrated discrimination improvement (IDI), net reclassification improvement
      (NRI(>0.01)) and categorical NRI. The analyses were illustrated by a simulation
      of atrial fibrillation risk prediction based on a published clinical risk model.
      RESULTS: We observed minimal improvement in AUC with the addition of rare
      variants. All measures increased with the frequency and OR of the variant, but
      maximum increment in AUC remained below 0.05. Increment in AUC and NRI(>0.01)
      decreased with higher AUC of the baseline model, whereas IDI remained constant.
      In the atrial fibrillation example, the maximum increment in AUC was 0.02 for a
      variant with frequency = 0.01 and OR = 10. IDI and NRI showed at most minimal
      increase for variants with frequency greater than or equal to 0.005 and OR
      greater than or equal to 5. CONCLUSIONS: Since rare variants are present in only
      a minority of affected individuals, their predictive ability is generally low at
      the population level. To improve the predictive ability of clinical risk models
      for complex diseases, genetic variants must be common and have substantial effect
      on disease risk.

PMID- 23961721
TI  - Cluster size effects in the photocatalytic hydrogen evolution reaction.
AB  - The photocatalytic water reduction reaction on CdS nanorods was studied as
      function of Pt cluster size. Maximum H2 production is found for Pt46. This effect
      is attributed to the size dependent electronic properties (e.g., LUMO) of the
      clusters with respect to the band edges of the semiconductor. This observation
      may be applicable for the study and interpretation of other systems and
      reactions, e.g. H2O oxidation or CO2 reduction. 

PMID- 23961722
TI  - Signal peptide etiquette during assembly of a complex respiratory enzyme.
AB  - Salmonella enterica serovar Typhimurium is a Gram-negative pathogen capable of
      respiration with a number of terminal electron acceptors. Tetrathionate reductase
      is important for the infection process and is encoded by the ttrBCA operon where
      TtrA and TtrB are metallocofactor-containing proteins targeted to the periplasmic
      side of the membrane by two different Tat targeting peptides. In this work, the
      inter-relationship between these two signal peptides has been explored. Molecular
      genetics and biochemical approaches reveal that the processing of the TtrB Tat
      signal peptide is dependent on the successful assembly of its partner protein,
      TtrA. Inactivation of either the TtrA or the TtrB Tat targeting peptides
      individually was observed to have limited overall effects on assembly of the
      enzyme or on cellular tetrathionate reductase activity. However, inactivation of
      both signal peptides simultaneously was found to completely abolish physiological
      tetrathionate reductase activity. These data suggest both signals are normally
      active during assembly of the enzyme, and imply a code of conduct exists between
      the signal peptides where one can compensate for inactivity in the other. Since
      it appears likely that tetrathionate reductase presents itself for export as a
      multi-signal complex, these observations also have implications for the mechanism
      of the bacterial Tat translocase. 

PMID- 23961723
TI  - NMR of short-chain hydrocarbons in nematic and smectic a liquid crystals.
AB  - The proton NMR spectra of ethane, propane, and n-butane codissolved and
      orientationally ordered in two liquid-crystal solvents that exhibit both nematic
      (N) and smectic A (SmA) phases (one of which also has a reentrant nematic (RN)
      phase) are analyzed using CMA-ES (covariance-matrix adaptation evolution
      strategy). To deal with problems arising from the broad liquid-crystal background
      signal, a smoothed experimental spectrum is fitted to a smoothed calculated
      spectrum. The ethane and propane dipolar couplings and anisotropic energy
      parameters scale with each other, and the n-butane couplings are assumed to
      behave likewise. This restriction on the relative values of the n-butane energy
      parameters facilitates a fit to the temperature dependence of the n-butane
      dipolar couplings, in which the six n-butane energy parameters (three for trans
      and three for gauche), the isotropic trans-gauche energy difference E(tg), and
      its temperature coefficient E(tg)', and the methyl CCH angle decrease are
      obtained. Unlike earlier studies, the fit does not employ a model for the
      anisotropic intermolecular potential. The nematic potential in the SmA phase of
      the liquid-crystal mixture 6OCB/8OCB is estimated by interpolated values obtained
      from the ethane spectra for the N and RN regions. Analysis of results for the SmA
      phase involves adding a nematic-smectic coupling prefactor and a smectic
      prefactor. Spectra obtained in the liquid-crystal 8OCB are calculated with no
      adjustable parameters, scaling the potentials using the ethane values, and the
      agreement between experiment and calculation is outstanding. Conformer
      populations are affected by the environment, and the isotropic solute-solvent
      interactions result in increased gauche populations, whereas anisotropic
      interactions increase the trans probability. The trans probability in the SmA
      phase is slightly lower than expected from the nematic results.

PMID- 23961724
TI  - Genetic variation in yield under hot ambient temperatures spotlights a role for
      cytokinin in protection of developing floral primordia.
AB  - Unusually hot ambient temperatures (HAT) can cause pre-anthesis abortion of
      flowers in many diverse species, limiting crop production. This limitation is
      becoming more substantial with climate change. Flower primordia of passion fruit
      (Passiflora edulis Sims) vines exposed to HAT summers, normally abort. Flower
      abortion can also be triggered by gibberellin application. We screened for, and
      identified a genotype capable of reaching anthesis during summer as well as
      controlled HAT conditions, and also more resistant to gibberellin. Leaves of this
      genotype contained higher levels of endogenous cytokinin. We investigated a
      possible connection between higher cytokinin levels and response to gibberellin.
      Indeed, the effects of gibberellin application were partially suppressed in
      plants pretreated with cytokinin. Can higher cytokinin levels protect flowers
      from aborting under HAT conditions? In passion fruit, flowers at a specific stage
      showed more resistance in response to HAT after cytokinin application. We further
      tested this hypothesis in Arabidopsis. Transgenic lines with high or low
      cytokinin levels and cytokinin applications to wild-type plants supported a
      protective role for cytokinin on developing flowers exposed to HAT. Such findings
      may have important implications in future breeding programmes as well as field
      application of growth regulators. 

PMID- 23961725
TI  - Identification of psoriatic patients at risk of high quality of life impairment.
AB  - Psoriasis is a systematic chronic disease with large influence on patients'
      quality of life (QoL). The aim of this study was to assess the QoL of patients
      with psoriasis using generic, dermatology-specific and psoriasis-specific
      instruments simultaneously, to investigate the relationships between dimensions
      or subscales of the questionnaires and to identify categories of patients at risk
      of a high QoL impairment. The study comprised 100 consecutive patients with
      psoriasis treated at the Department of Dermatology, Clinical Center "Zvezdara",
      Belgrade, from January to December 2011. Three QoL questionnaires were
      administered: the EuroQol-5D (EQ-5D), the Dermatological Life Quality Index
      (DLQI) and the Psoriasis Disability Index (PDI). The Psoriasis Area and Severity
      Index was used in evaluating disease severity. According to our results the QoL
      of psoriatic patients was impaired (the overall DLQI and PDI scores were 10.5 +/-
      7.2 and 13.4 +/- 8.7, respectively, while EQ visual analog scale score was 48.8
      +/- 25.1). The most predictive factor of QoL impairment was disease severity,
      followed by sole and nail involvement. Psoriatic arthritis and bleeding were also
      associated with impaired QoL. Significant correlations between the instruments
      used in this study were in the expected directions. Mainly strong and moderate
      significant correlations ranging 0.26-0.84 were seen between DLQI and PDI
      instruments. A detailed approach to QoL assessment may give to the dermatologist
      useful information that could be of help in identifying patients belonging to
      categories at risk of high QoL impairment due to psoriasis, thus guiding them in
      clinical practice.

PMID- 23961727
TI  - Scene-specific memory for objects: a model of episodic memory impairment in
      monkeys with fornix transection.
AB  - Abstract A series of five experiments investigated the relationship between
      object memory and scene memory in normal and fornix-transected monkeys. An
      algorithm created formally defined background and objects on a large visual
      display; the disposition of some particular objects in particular places in a
      particular background constitutes a formally defined scene. The animals learned
      four types of discrimination problem: (1) object-in-place discrimination
      learning, in which the correct (rewarded) response was to a particular object
      that always occupied the same place in a particular unique background, (2) place
      discrimination learning, in which the correct response was to a particular place
      in a unique background, with no distinctive object at that place, (3) object
      discrimination learning in unique backgrounds, in which the correct response was
      to a particular object that could occupy one or the other of two possible places
      in a unique background, and (4) object discrimination learning in varying
      backgrounds, in which the correct response was to a particular object that could
      appear at any place in any background. The severest impairment produced by fornix
      transection was in object-in-place learning. Fornix transection did not impair
      object discrimination learning in varying backgrounds. The results from the other
      two types of learning task showed intermediate severity of impairment in the
      fornix-transected animals. The idea that fornix transection in the monkey impairs
      spatial memory but leaves object memory intact is thus shown to be an
      oversimplification. The impairments of object memory in the present experiments
      are analogous to the impairments of episodic memory seen in human amnesic
      patients. 

PMID- 23961728
TI  - Dissociation of motor hyperactivity and spatial memory deficits by selective
      hippocampal lesions in the neonatal rat.
AB  - Abstract Hippocampal lesions can disrupt the acquisition of new memories and tend
      to increase motor activity. Although hyperactivity may affect exploration, it is
      unclear how these performance variables contribute to the learning deficit and it
      is also not known which brain structures are involved. The present study provides
      evidence for a dissociation between activity and memo?. Following unilateral or
      bilateral electrolytic lesions of the hippocampus in neonatal rats, we assessed
      open field behavior and performance of discrete trials alternation in a T-maze.
      When tested 6 and 20 weeks postoperatively, rats subjected to bilateral lesions
      were hyperactive. Their performance in the discrete trials alternation task was
      impaired. In contrast, rats subjected to unilateral lesions did not display an
      increase in motor activity, but were still deficient in performance on the T
      maze. To define whether these behavioral changes were accompanied by secondary
      changes in structures that project to the hippocampus, we studied the function of
      the septum and locus coeruleus after the lesions. Septal choline acetyltrans
      ferase (CAT, the acetylcholine-synthesizing enzyme) activity was reduced and
      tyrosine hydroxylase (TH, the rate-limiting enzyme in catecholamine biosynthesis)
      activity in noradrenergic lc neurons was increased after both the unilateral and
      bilateral lesion. Therefore, these changes may contribute to the memory
      impairment but are not necessarily related to motor hyperactivity. We conclude
      that a deficit in spatial memory is not attributable to altered performance
      variables such as activity. Furthermore, spatial memory deficits in both the
      unilateral and bilateral lesion paradigms may be associated with changes in
      septal and lc function. 

PMID- 23961726
TI  - Treatment retention among patients randomized to buprenorphine/naloxone compared
      to methadone in a multi-site trial.
AB  - AIMS: To examine patient and medication characteristics associated with retention
      and continued illicit opioid use in methadone (MET) versus buprenorphine/naloxone
      (BUP) treatment for opioid dependence. DESIGN, SETTINGS AND PARTICIPANTS: This
      secondary analysis included 1267 opioid-dependent individuals participating in
      nine opioid treatment programs between 2006 and 2009 and randomized to receive
      open-label BUP or MET for 24 weeks. MEASUREMENTS: The analyses included measures
      of patient characteristics at baseline (demographics; use of alcohol, cigarettes
      and illicit drugs; self-rated mental and physical health), medication dose and
      urine drug screens during treatment, and treatment completion and days in
      treatment during the 24-week trial. FINDINGS: The treatment completion rate was
      74% for MET versus 46% for BUP (P < 0.01); the rate among MET participants
      increased to 80% when the maximum MET dose reached or exceeded 60 mg/day. With
      BUP, the completion rate increased linearly with higher doses, reaching 60% with
      doses of 30-32 mg/day. Of those remaining in treatment, positive opioid urine
      results were significantly lower [odds ratio (OR) = 0.63, 95% confidence interval
      (CI) = 0.52-0.76, P < 0.01] among BUP relative to MET participants during the
      first 9 weeks of treatment. Higher medication dose was related to lower opiate
      use, more so among BUP patients. A Cox proportional hazards model revealed
      factors associated with dropout: (i) BUP [versus MET, hazard ratio (HR) = 1.61,
      CI = 1.20-2.15], (ii) lower medication dose (<16 mg for BUP, <60 mg for MET; HR =
      3.09, CI = 2.19-4.37), (iii) the interaction of dose and treatment condition
      (those with higher BUP dose were 1.04 times more likely to drop out than those
      with lower MET dose, and (iv) being younger, Hispanic and using heroin or other
      substances during treatment. CONCLUSIONS: Provision of methadone appears to be
      associated with better retention in treatment for opioid dependence than
      buprenorphine, as does use of provision of higher doses of both medications.
      Provision of buprenorphine is associated with lower continued use of illicit
      opioids.

PMID- 23961729
TI  - Temporal integration in sensorimotor synchronization.
AB  - Abstract The concept of a temporal integration process in the timing mechanisms
      in the brain, postulated on the basis of experimental observations from various
      paradigms (for a review see P$oUppel, 1978), has been explored in a sensorimotor
      synchronization task. Subjects synchronized their finger taps to sequences of
      auditory stimuli with interstimulus-onset intervals (ISIs) between 300 and 4800
      msec in different trials. Each tonal sequence consisted of 110 stimuli; the tones
      had a frequency of 500 Hz and a duration of 100 msec. As observed previously,
      response onsets preceded onsets of the stimuli by some tens of milliseconcls for
      ISIs in the range from about 600 to 1800 msec. For ISIs longer than or equal to
      2400 msec, the ability to time the response sequence in such a way that the
      response 5 were placed right ahead of the stimuli started to break clown, i.e.,
      the task was fulfilled by reactions to the stimuli rather than by advanced
      responses. This observation can he understood within the general framework of a
      temporal integration puce 55 that is supposed to have a maximal capacity
      (integration interval) of approximately 3 sec. Only if successive stimuli fall
      within one integration period, can motor programs be initiated properly by a
      prior stimulus and thus lead to an appropriate synchronization between the
      stimulus sequence and corresponding motor acts. 

PMID- 23961730
TI  - Neural Representations for Sensorimotor Control. III. Learning a Body-Centered
      Representation of a Three-Dimensional Target Position.
AB  - Abstract A neural model is described of how the brain may autonomously learn a
      body-centered representation of a three-dimensional (3-D) target position by
      combining information about retinal target position, eye position, and head
      position in real time. Such a body-centered spatial representation enables
      accurate movement commands to the limbs to be generated despite changes in the
      spatial relationships between the eyes, head, body, and limbs through time. The
      model learns a vector representation-otherwise known as a parcellated distributed
      representation-of target vergence with respect to the two eyes, and of the
      horizontal and vertical spherical angles of the target with respect to a
      cyclopean egocenter. Such a vergence-spherical representation has been reported
      in the caudal midbrain and medulla of the frog, as well as in psychophysical
      movement studies in humans. A head-centered vergence-spherical representation of
      foveated target position can be generated by two stages of opponent processing
      that combine corollary discharges of outflow movement signals to the two eyes.
      Sums and differences of opponent signals define angular and vergence coordinates,
      respectively. The head-centered representation interacts with a binocular visual
      representation of nonfoveated target position to learn a visuomotor
      representation of both foveated and nonfoveated target position that is capable
      of commanding yoked eye movements. This head-centered vector representation also
      interacts with representations of neck movement commands to learn a body-centered
      estimate of target position that is capable of Commanding coordinated arm
      movements. Learning occurs during head movements made while gaze remains fixed on
      a foveated target. An initial estimate is stored and a VOR-mediated gating signal
      prevents the stored estimate from being reset during a gaze-maintaining head
      movement. As the head moves, new estimates are compared with the stored estimate
      to compute difference vectors which act as error signals that drive the learning
      process, as well as control the on-line merging of multimodal information. 

PMID- 23961731
TI  - A model of the learning of arm trajectories from spatial deviations.
AB  - Abstract Unconstrained point-to-point reaching movements performed in the
      horizontal plane tend to follow roughly straight hand paths with smooth, bell
      shaped velocity profiles. The objective of the research reported here was to
      explore the hypothesis that these data reflect an underlying learning process
      that prefers simple paths in space. Under this hypothesis, movements are learned
      based only on spatial errors between the actual hand path and a desired hand
      path; temporally varying targets are not allowed. We designed a neural network
      architecture that learned to produce neural commands to a set of muscle-like
      actuators based only on information about spatial errors. Following repetitive
      executions of the reaching task, the network was able to generate point-to-point
      horizontal arm movements and the resulting muscle activation patterns and hand
      trajectories were found to be similar to those observed experimentally for human
      subjects. The implications of our results with respect to current theories of
      multijoint limb movement generation are discussed. 

PMID- 23961732
TI  - Mechanisms of spatial attention: the relation of macrostructure to microstructure
      in parietal neglect.
AB  - Abstract Parietal-damaged patients respond abnormally slowly to targets presented
      in the affected hemifield when preceded by cues in the intact hemifield. This
      inability to disengage attention from the ipsilesional field to reengage it in
      the contralesional field has been interpreted as evidence for a distinct
      "disengage" mechanism, localized in parietal cortex. We present a computational
      model that accounts for normal attentional effects by interactivity and
      competition among representations of different locations in space, without a
      dedicated "disengage" mechanism. We show that when the model is lesioned, it
      produces the "disengage deficit" shown by parietal-damaged patients. This
      suggests that the deficit observed in such patients can be understood as an
      emergent property of interactions among the remaining parts of the system, and
      need not imply the existence of a dedicated "disengage" mechanism in the normal
      brain. 

PMID- 23961733
TI  - ERP Evidence for a Shifting Attention Deficit in Patients with Damage to the
      Cerebellum.
AB  - Abstract In a previous study, we found that patients with damage to the
      neocerebellum were significantly impaired in the ability to rapidly shift their
      attention between ongoing sequences of auditory and visual stimuli (Akshoomoff &
      Courchesne, 1992). In the present study, young patients with damage to the
      neoccrebelluni were found to be impaired in rapidly shifting their mention
      between visual stimuli that occurred within a single location. Event-related
      potentials recorded during the shifting attention experiment suggested that this
      reflects a deficit in the. covert ability to selectively activate and deactivate
      attention. These results lend Further support to the hypothesis that the
      neocerebellum plays a role in the ability to rapidly shift attention. 

PMID- 23961734
TI  - Endogenously generated and visually guided saccades after lesions of the human
      frontal eye fields.
AB  - Abstract Nine patients with chronic, unilateral lesions of the dorso-lateral
      prefrontal cortex including the frontal eye fields (FEF) made saccades toward
      contralesional and ipsilesional fields. The saccades were either voluntarily
      directed in response to arrows in the center of a visual display, or were
      reflexively summoned by a peripheral visual signal. Saccade latencies were
      compared to those made by seven neurologic control patients with chronic,
      unilateral lesions of dorsolateral prefrontal cortex sparing the FEF, and by 13
      normal control subjects. In both the normal and neurologic control subjects,
      reflexive saccades had shorter Latencies than voluntary saccades. In the FEF
      lesion patients, voluntary saccades had longer latencies toward the
      contralesional field than toward the ipsilesional field. The opposite pattern was
      found for reflexive saccades: latencies of saccades to targets in the
      contralesional field were shorter than saccades summoned to ipsilesional targets.
      Reflexive saccades toward the ipsilesional field had abnormally prolonged
      latencies; they were comparable to the latencies observed for voluntary Saccades.
      The effect of FEF lesions on saccacles contrasted with those observed in a second
      experiment requiring a key press response: FEF lesion patients were slower in
      making key press responses to signals detected in the contralesional field. To
      assess covert attention and preparatory set the effects of precues providing
      advance information were measured in both saccade and key press experiments.
      Neither patient group showed any deficiency in using precues to shift attention
      or to prepare saccades. The FEF facilitates the generation of voluntary saccatles
      and also inhibits reflexive saccades to exogenous signals. FEF lesions may
      disinhibit the ipsilesional midbrain which in turn may inhibit the opposite
      colliculus to slow reflexive saccades toward the ipsilesional field. 

PMID- 23961735
TI  - A dynamic systems approach to development: applications.

PMID- 23961736
TI  - When should women be recruited to intrapartum research projects? A retrospective
      review.
AB  - OBJECTIVE: To review and describe the impact of varied recruitment processes in
      two intrapartum studies. DESIGN: Retrospective review of one prospective cohort
      study and one pilot randomized controlled trial. SETTING: Australian tertiary
      referral hospital. POPULATION: Women with term, cephalic singleton pregnancies.
      METHODS: Recruitment processes in one observational and one interventional study
      examining the management of occipitoposterior position in labor were reviewed.
      Data concerning recruitment and serial attrition for these studies were
      collected. The value of allowing consent in early labor in addition to consent in
      the antenatal period was assessed. MAIN OUTCOME MEASURE: Relative proportions of
      women participating compared with the numbers approached and recruited. RESULTS:
      One in 48 women approached about the observational study agreed to participate
      and then had a fetus in occipitoposterior position. One in 33 women in the
      intervention study were eventually randomized. Women approached in early labor
      were more likely to agree to participate (77% vs. 58%; p < 0.0001), more likely
      to have an ultrasound scan during labor (40% vs. 15%; p < 0.0001) and more likely
      to be randomized to intervention (4% vs. 1.5%; p = 0.02). CONCLUSION: Intrapartum
      research is associated with low rates of recruitment and these rates may be
      improved by asking women to provide informed consent during labor rather than the
      antenatal period. It is important to consider ways to facilitate randomized
      controlled trials involving women in labor to advance evidence-based care in this
      environment. This should include prospective research that seeks to define the
      best approach to patient recruitment.

PMID- 23961737
TI  - Using a standardized method for laparoscopic cholecystectomy to create a concept
      operation-specific checklist.
AB  - OBJECTIVES: Prevalences of bile duct injury (BDI) following laparoscopic
      cholecystectomy (LC) remain unacceptably high. There is no standardized method
      for performing an LC. This study aims to describe a standardized technique for LC
      that will allow for the development of a concept LC checklist, the use of which,
      it is hoped, will decrease the prevalence of BDI. METHODS: A standardized method
      for LC was developed based on previously published expert analysis supplemented
      by video error analysis of operations in which BDI occurred. Established
      checklist methodology was then used to construct an LC-specific concept
      checklist. RESULTS: A five-step technique for the safe establishment of the
      critical view was created to guide the development of the checklist. The five
      steps are: (i) confirm the gallbladder lies in the hepatic principal plane and is
      retracted to the 10 o'clock position; (ii) confirm Hartmann's pouch is lifted up
      and toward the segment IV pedicle; (iii) identify Rouviere's sulcus; (iv) confirm
      the release of the posterior leaf of the peritoneum covering the hepatobiliary
      triangle, and (v) confirm the critical view with or without intraoperative
      cholangiography. CONCLUSIONS: A standardized approach to LC would allow for the
      creation of an LC-specific checklist that has the potential to lower the
      prevalence of BDI.

PMID- 23961738
TI  - Role of infection control in prevention of hepatitis B virus (HBV) in
      hemodialysis (HD) patients.
AB  - Hemodialysis (HD) patients are particularly vulnerable to Hepatitis B virus (HBV)
      and have less sustained and lower antibody response to HBV vaccination. Among
      blood-borne pathogens, HBV can stay alive on environmental surfaces for over a
      week. The incidence of HBV was extremely high among HD patients. HBV vaccination,
      screening of blood products and infection control measures lead to significant
      decrease of HBV among HD patients. The infection control measures include;
      Medication safety and injection practices, environmental cleaning and
      disinfection, reuse of dialyzers for same patients, hand hygiene, isolation and
      barrier precautions, HBV vaccination and routine serology checking, assuring HBV
      immune status for HD unit staff, transmission based precautions and outbreak
      management. 

PMID- 23961739
TI  - Role of ultraviolet (UV) disinfection in infection control and environmental
      cleaning.
AB  - Ultraviolet (UV) radiation is capable of disinfecting surfaces, water and air.
      The UV technology was used for many years. However, safer and more effective
      delivery systems of UV radiation, make it a very useful option for disinfection.
      Effective disinfection of environmental surfaces is a key step in the prevention
      of spread of infectious agents. The traditional manual cleaning is essential in
      assuring adequate elimination of contamination. However, terminal cleaning is
      frequently suboptimal or unpredictable in many circumstances. UV&#45;C radiation
      is an adjunctive disinfectant new technology that could kill a wide array of
      microorganisms including both vegetative and spore forming pathogens. The
      technology is getting more affordable and has produced consistent reproducible
      significant reduction of bacterial contamination. 

PMID- 23961740
TI  - Opening Pandora's (tool) Box: health care construction and associated risk for
      nosocomial infection.
AB  - There are approximately 5,700 hospitals in the United States, 3,000-4,000 that
      are antiquated or obsolescing. To meet increased service demands, remain
      financially viable; meet needs to upgrade aging infrastructure and incorporate
      medical and technology advancements, healthcare facilities are in a perpetual
      state of construction. Outbreaks of nosocomial infections have historically been
      documented in association with construction and renovation actives within health
      care facilities. For most healthy individuals, environmental exposures to
      etiological agents, results in no adverse effects but in immune-compromised
      patient, they are left susceptible to inadvertent exposures during construction
      to opportunistic bacteria, fungi and viruses. Evidence scientifically linking
      construction work and nosocomial infections as well as the efficacy and clinical
      relevance of infection control precautions is somewhat lacking but the empirical
      evidence and recommendations to support protective measures is steadily growing.
      Opening a "Pandora's Box" during construction can unleash unintended consequences
      therefore; it is imperative that a thorough, multidisciplinary approach towards
      an infection control plan is put clearly and firmly in place allowing health care
      construction projects to move forward with confidence that patient safety is the
      first specification. 

PMID- 23961741
TI  - Monochloramine use for prevention of Legionella in hospital water systems.
AB  - Eradication of Legionella species from water distribution systems especially in
      hospital settings has proven to be challenging. Legionella species causes
      Legionnaire's disease that is a potentially fatal respiratory disease often
      acquired through the aerosolization of contaminated water. Monochloramine has
      been used successfully in the municipal water systems to eradicate Legionella and
      there is currently limited data to support its use in the hospital setting. This
      technology appears to be affordable, safe and effective at penetrating biofilm in
      water distribution systems. 

PMID- 23961742
TI  - Simulation-based assessment of paramedics and performance in real clinical
      contexts.
AB  - OBJECTIVE: The objective of this study was to seek validity evidence for
      simulation-based assessments (SBA) of paramedics by asking to what extent the
      measurements obtained in SBA of clinical competence are associated with
      measurements obtained in actual paramedic contexts, with real patients. METHODS:
      This prospective observational study involved analyzing the assessment of
      paramedic trainees at the entry-to-practice level in both simulation- and
      workplace-based settings. The SBA followed an OSCE structure involving full
      clinical cases from initial patient contact to transport or transfer of care. The
      workplace-based assessment (WBA) involved rating samples of clinical performance
      during real clinical encounters while assigned to an emergency medical service.
      For each candidate, both assessments were completed during a 3-week period at the
      end of their training. Raters in the SBA and WBA settings used the same paramedic
      specific seven-dimension global rating scale. Reliability was calculated and
      decision studies were completed using generalizability theory. Associations
      between settings (overall and by dimension) were calculated using Pearson's
      correlation. RESULTS: A total of 49 paramedic trainees were assessed using both a
      SBA and WBA. The mean score in the SBA and WBA settings were 4.88 (SD = 0.68) and
      5.39 (SD = 0.48), respectively, out of a possible 7. Reliability for the SBA and
      WBA settings reached 0.55 and 0.49, respectively. A decision study revealed 10
      and 13 cases would be needed to reach a reliability of 0.7 for the SBA and WBA
      settings. Pearson correlation reached 0.37 (p = 0.01) between settings, which
      rose to 0.73 when controlling for imperfect reliability; five of seven dimensions
      (situation awareness, history gathering, patient assessment, decision making, and
      communication) reaching significance. Two dimensions (resource utilization and
      procedural skills) did not reach significance. CONCLUSION: For five of the seven
      dimensions believed to represent the construct of paramedic clinical performance,
      scores obtained in the SBA were associated with scores obtained in real clinical
      contexts with real patients. As SBAs are often used to infer clinical competence
      and predict future clinical performance, this study contributes validity evidence
      to support these claims as long as the importance of sampling performance broadly
      and extensively is appreciated and implemented.

PMID- 23961743
TI  - Teacher versus peer models.
AB  - Female Ss (N=80) observed either a teacher or a peer model (M) demonstrate a
      motor task with either high or low performance ability. The effects' of viewing
      these live performances on S's subsequent motor performances were examined. After
      the observation of M, S's performance in the presence or absence of the observed
      M was investigated. A Control Group consisting of 20 Ss, viewing no M, was
      compared to ail other groups for analysis. Results of the M Type * M's Ability
      Level * M Presence design indicated that those in the Control Group had
      significantly lower performances than all other groups on all blocks of trials.
      In addition, across all trial blocks, S's performances were enhanced subsequent
      to having viewed a skillful teacher M. Upon observing M's demonstration, Ss
      exhibited increased matching responses and better performances when performing in
      the presence of M. 

PMID- 23961744
TI  - Absolute error.
AB  - School of Physical Education and Recreation The University of British Columbia
      The purpose of this investigation was to re-examine the measures of algebraic
      error (CE), absolute error (AE), and within-S variance (VE). in an attempt to
      arrive at unambiguous definitions regarding the statistical and logical meanings
      of these three performance variables. Under the assumption of a normal
      distribution, the statistic AE is completely dependent on CE and VE and thus can
      be predicted from them. This shows that all information contained in the term AE
      is contained in either CE (when the ratio C E / V E   >   2 .0 ), or in VE (when
      CE ? 0.0) or in a weighted combination of both CE and VE (when 0 < C E / V E <  
      2.0 ). Examples are provided to show the type of errors made in interpreting
      significant findings when AE is the dependent variable. 

PMID- 23961745
TI  - Further tests of adams' closed-loop theory.
AB  - To test Adams' closed-loop theory of motor learning, which postulates a memory
      trace for response production and a perceptual trace for response evaluation, Ss
      in two experiments performed a ballistic manual response wherein a 26-in.
      movement was attempted in exactly 200 msec. Feedback (presence or absence of
      vision and audition on all trials) and KR (presence or absence of KR from E on
      Trials 20-45) were manipulated in a 2*2 design. KR withdrawal produced marked
      decrements in performance, with greater decrements for the limited feedback
      condition. The error detection mechanism developed over trials but was not
      dependent upon vision and audition. Findings provided mixed support for Adams'
      closed-loop theory. 

PMID- 23961746
TI  - The temporal placement of interpolated movements in short-term motor memory .
AB  - Directional response biasing as a function of the recency of an interpolated act
      was examined on a lever device in a within-S design. The temporal occurrence of
      an interpolated act was systematically varied (5, 30, or 55 sec. after the
      criterion act) for three retention intervals (15, 40, and 65 sec.), and the
      location of the interpolated movement was held constant +/- 40 deg. from the
      criterion position. Analysis of constant errors showed significant positive
      directional biasing for interpolated acts greater than criterion positions.
      Further analyses at the 40-and 65-sec. retention intervals supported a recency
      interpretation. As the retention interval increased, the positive constant error
      was maintained for interpolated acts with the same post-biasing interval, whereas
      constant error became increasingly negative as the post-biasing interval
      increased. Examination of variable error revealed a slight increase over time and
      no significant differences between directional conditions. The recency findings
      were discussed in terms of the view that reproduction of a criterion act is
      dependent on the relative decay states between the interpolated and criterion
      traces. 

PMID- 23961747
TI  - Movement time in an underwater environment.
AB  - The effect of an underwater environment on the human motor capacity, as measured
      by Fitts' Law, was determined. Five Ss performed a reciprocal tapping task both
      on land and underwater. The results showed that movement time (MT) was
      significantly slower (p < 01) underwater than on land. Underwater the amplitude
      of the movement was found to have a greater influence on MT than the required
      precision of the movement. On land the reverse was found to be true with movement
      precision having a greater influence on MT. 

PMID- 23961748
TI  - Length of time necessary to view a ball while catching it.
AB  - College women (N=65) attempted to catch a tennis ball rebounding from a wall to
      which the ball was projected from a pitching machine. Ss were permitted to see
      the ball at the end of flight for 0.5, 0.4, 0.3, 0.25, or 0.2 sec. There were
      significant differences among each of the conditions, with increased viewing time
      yielding increased catching success. The correlation coefficients between a
      measure of simple reaction time and catching success during these five conditions
      ranged from .04 to -.68. 

PMID- 23961749
TI  - Involuntary rest pauses (irps) in schizophrenics and normals.
AB  - Normal and schizophrenic Ss (N=24 each) performed a simple tapping task. The
      prediction that more involuntary rest pauses would be produced by schizophrenics
      than by normals was borne out. A discussion is given of the relation of these
      results to the interpretation of schizophrenia in terms of "arousal". 

PMID- 23961750
TI  - Do rats have prefrontal cortex? The rose-woolsey-akert program reconsidered.
AB  - Abstract Primates are unique among mammals in possessing a region of dorsolateral
      prefrontal cortex with a well-developed internal granular layer. This region is
      commonly implicated in higher cognitive functions. Despite the histological
      distinctiveness of primate dorsolateral prefrontal cortex, the work of Rose,
      Woolsey, and Akert produced a broad consensus among neuroscientists that
      homologues of primate granular frontal cortex exist in nonprimates and can be
      recognized by their dense innervation from the mediodorsal thalamic nucleus (MD).
      Additional characteristics have come to be identified with dorsolateral
      prefrontal cortex, including rich dopaminergic innervation and involvement in
      spatial delayed-reaction tasks. However, recent studies reveal that these
      characteristics are not distinctive of the dorsolateral prefrontal region in
      primates: MD and dopaminergic projections are widespread in the frontal lobe, and
      medial and orbital frontal areas may play a role in delay tasks. A reevaluation
      of rat frontal cortex suggests that the medial frontal cortex, usually considered
      to be homologous to the dorsolateral prefrontal cortex of primates, actually
      consists of cortex homologous to primate premotor and anterior cin-date cortex.
      The lateral MD-projection cortex of rats resembles portions of primate orbital
      cortex. If prefrontal cortex is construed broadly enough to include orbital and
      cingulate cortex, rats can be said to have prefrontal cortex. However, they
      evidently lack homologues of the dorsolateral prefrontal areas of primates. This
      assessment suggests that rats probably do not provide useful models of human
      dorsolateral frontal lobe function and dysfunction, although they might prove
      valuable for understanding other regions of frontal cortex. 

PMID- 23961751
TI  - Central auditory system plasticity associated with speech discrimination
      training.
AB  - Abstract A passively elicited cortical potential that reflects the brain's
      discrimination of small acoustic contrasts was measured in response to two
      slightly different speech stimuli in adult human subjects. Behavioral training in
      the discrimination of those speech stimuli resulted in a significant change in
      the duration and magnitude of the cortical potential. The results demonstrate
      that listening training can change the neurophysiologic responses of the central
      auditory system to just-perceptible differences in speech. 

PMID- 23961752
TI  - Semantic facutation in aphasia: effects of time and expectancy.
AB  - Abstract Two auditory lexical decision semantic priming experiments were
      conducted to examine the extent to which the automaticcontrolled processing
      dichotomy can characterize lexical access deficits in Broca's and Wernicke's
      aphasics. In Experiment 1, prime-target predictability was varied while the
      interval between prime and target (ISI) was held constant. In Experiment 2, ISI
      was varied while prime-target predictability was held constant. The pattern of
      semantic facilitation and inhibition results for Experiment 1 showed that Broca's
      aphasics were influenced by prime-target predictability, whereas Wernicke's
      aphasics were not. In contrast in hperiment 2, manipulations of ISI at 150 and
      2000 msec did not affect patterns of semantic facilitation for either Broca's or
      Wernicke's aphasics. Taken together, the results of these two experiments suggest
      that Broca's aphasics use heuristic strategies more so than old and young normal
      subjects. In addition, they seem to have an automatic processing deficit
      affecting the level of activation of lexical entries, with a spared time course
      of activation. Wernicke's aphasics show a pattern of results consistent with the
      view that automatic processing is unimpaired in these patients, while they fail
      to use heuristic strategies in these tasks. 

PMID- 23961753
TI  - Distinct Cortical Activation Patterns during Long-Term Memory Retrieval of
      Verbal, Spatial, and Color Information.
AB  - Abstract Slow, DC-like event-related brain potentials (ERPs) were recorded from
      the scalp of 30 healthy young adults to test the hypothesis that distinct
      cortical areas are activated when different types of information are retrieved
      from long-term memory. Three groups of 10 subjects each were first trained with
      associations between either pictures and spatial positions (spatial condition),
      pictures and color patches (color condition), or nouns and nouns (verbal
      condition). All three experimental conditions were completely analogous with
      respect to the established associative structure, the learning procedure, the
      performance criterion, and the retrieval test that followed 1 day after learning.
      Slow event-related brain potentials being recorded during retrieval had a
      significantly distinct topography. The maximum of a DC-like negative wave was
      found in the verbal condition over the left frontal, in the spatial condition
      over the parietal, and in the color condition over the right occipital to
      temporal cortex. These results are consistent with the idea that memory
      representations are either "down-loaded" into or directly reactivated within
      those cortical processing modules in which the same material was handled during
      perception. Response times, on the other hand, revealed no difference between the
      three retrieval conditions. In each case RT increased monotonically, if more
      items had to be scanned. Thus, while the ERPs suggest the involvement of
      different cortical processors during memory search the response times suggest
      that a sequentially operating scanning mechanism applies to all of them. 

PMID- 23961754
TI  - Memory representations in natural tasks.
AB  - Abstract The very limited capacity of short-term or working memory is one of the
      most prominent features of human cognition. Most studies have stressed delimiting
      the upper bounds of this memory in memorization tasks rather than the performance
      of everyday tasks. We designed a series of experiments to test the use of short
      term memory in the course of a natural hand-eye task where subjects have the
      freedom to choose their own task parameters. In this case subjects choose not to
      operate at the maximum capacity of short-term memory but instead seek to minimize
      its use. In particular, reducing the instantaneous memory required to perform the
      task can be done by serializing the task with eye movements. These eye movements
      allow subjects to postpone the gathering of task-relevant information until just
      before it is required. The reluctance to use short-term memory can be explained
      if such memory is expensive to use with respect to the cost of the serializing
      strategy. 

PMID- 23961755
TI  - The nature of preattentive storage in the auditory system.
AB  - Abstract Event-related potentials were recorded to tones that subjects ignored
      while reading a book of their choosing. In all conditions, 90% of the tones were
      100 msec in duration and 10% of the tones were 170 msec in duration. In a control
      condition, a customary oddball paradigm was used in which all of the tones were
      identical except for the longer duration tones. In two conditions, the tones
      varied over a wide range of tonal frequencies from 700 to 2050 Hz in 10 steps of
      150 Hz. In another condition, the tones varied over the same frequencies but also
      varied in intensity from about 60 to 87 dB in steps of 3 dB. Thus, there was no
      "standard" tone in the sense of a frequently presented tone that had identical
      stimulus features. A mismatch negativity (MMN) was elicited in all conditions.
      The data are discussed in terms of the storage of information in the memory upon
      which the MMN is based. 

PMID- 23961756
TI  - On neural codes and perception.
AB  - Abstract Bill Newsome is a professor in the Department of Neurobiology at the
      Stanford University School of Medicine. He received his B.S. in physics from
      Stetson University in 1974 and his Ph.D. in biology from Caltech in 1980.
      Following postdoctoral work at MH, he served on the faculty at SUNY Stony Brook
      before joining the Stanford faculty in 1988. His research has focused on the
      neural mechanisms underlying visual perception and visually guided behavior. Bill
      was a corecipient of the Rank Prize in optoelectronics in 1992, and received the
      Minerva Foundation's Golden Brain Award in the same year. This fall he received
      the Spencer Award, granted yearly by the College of Physicians and Surgeons at
      Columbia University for highly original contributions to research in
      neurobiology. In addition, he won the Kaiser Award for excellence in preclinical
      teaching granted annually by the Stanford School of Medicine. 

PMID- 23961757
TI  - A Dynamic Systems Approach to Development: Applications; The Language
      InstinctPatterns in the Mind. Language and Human Nature The Language Instinct.

PMID- 23961759
TI  - Superior properties of silica thin films prepared from perhydropolysilazane
      solutions at room temperature in comparison with conventional alkoxide-derived
      silica gel films.
AB  - Preparation of silica thin films from perhydropolysilazane (PHPS) at room
      temperature has attracted much attention because it provides a new way to realize
      silica thin films in a variety of technologies where any high temperature
      processes should be avoided. Although silica gel films can also be prepared from
      alkoxides at room temperature by conventional sol-gel method, they are believed
      to have low mechanical and chemical durability. However, even such alkoxide
      derived silica gel films have possibilities to become more durable via
      condensation reaction and densification when aged at room temperature. In order
      to clarify whether or not PHPS-derived silica thin films have critical
      superiority on properties, the hardness and chemical durability were compared
      between PHPS- and alkoxide-derived silica thin films, where PHPS films were
      exposed to the vapor from aqueous ammonia at room temperature for PHPS-to-silica
      conversion. Alkoxide-derived silica gel films were found to be densified and
      hardened when stored in air at room temperature, which resulted in pencil
      hardness even higher than 9H on Si(100) substrates. However, the ultra
      microindentation tests demonstrated that the PHPS-derived films are definitely
      harder than the alkoxide-derived ones. The PHPS-derived films were also found to
      have higher chemical durability in water and in aqueous ammonia. Such higher
      mechanical and chemical durability of the PHPS-derived films was ascribed to
      their higher density, i.e., more highly condensed states, which was evidenced in
      infrared absorption spectra. Hard coating performance on plastic substrates was
      also studied, and the PHPS-derived films were demonstrated to have much higher
      adhesive strength on polymethylmethacrylate substrates. The in-plane stress
      measurement demonstrated that the PHPS-derived films have much lower or even
      negligible tensile stress, which may be one of the causes for such higher
      adhesive strength. 

PMID- 23961760
TI  - The preparation of trisubstituted alkenyl nucleoside phosphonates under
      ultrasound-assisted olefin cross-metathesis.
AB  - Intermolecular ultrasound-assisted olefin cross-metathesis is reported. This
      approach allows an easy access to challenging trisubstituted alkenyl nucleoside
      phosphonates. Regioselective chemoenzymatic deacetylation and Mitsunobu coupling
      are also described. 

PMID- 23961761
TI  - Interplay between chemical composition and cation ordering in the magnetism of
      Ni/Fe layered double hydroxides.
AB  - We report the synthesis of a family of ferrimagnetic NiFe layered double
      hydroxides (LDHs) with a variable Ni(2+)/Fe(3+) in-plane composition of [Ni(1
      x)Fe(x)(OH)2](CO3)(x/2).yH2O (x = 0.20, 0.25, and 0.33) by following a modified
      homogeneous precipitation. These layered magnets display high crystallinity,
      homogeneous hexagonal morphologies, and micrometric size that enable their
      quantitative exfoliation into single layers by sonomechanical treatment of the
      solids in polar solvents. This was confirmed by dynamic light scattering, UV-vis
      spectroscopy, high-resolution transmission electron miscroscopy, and atomic force
      microscopy methodologies to study the resulting steady suspensions. Our magnetic
      study reflects that the iron content in the LDH layers controls the overall
      magnetism of these lamellae. Hence, the gradual replacement of Ni(2+) with Fe(3+)
      centers introduces a larger amount of antiferromagnetically coupled Fe-OH-Fe
      pairs across the layers, provoking that the compound with the highest Fe/Ni ratio
      displays spontaneous magnetization at higher temperatures (T(irr) = 15.1 K) and
      the hardest coercive field (3.6 kG). Mossbauer spectroscopy confirms that the
      cation distribution in the layers is not random and reflects the occurrence of Fe
      clustering due to the higher affinity of Fe(3+) ions to accommodate other
      homometallic centers in their surroundings. In our opinion, this clarifies the
      origin of the glassy behavior, also reported for other magnetic LDHs, and points
      out spin frustration as the most likely cause.

PMID- 23961762
TI  - Toward understanding the influence of intermolecular interactions and molecular
      orientation on the chemical enhancement of SERS.
AB  - Implementation of SERS as an analytical technique is limited because the factors
      that govern the enhancement of individual vibrational modes are not well
      understood. Although the chemical effect only accounts for up to two orders of
      magnitude enhancement, it can still have a significant impact on the consistency
      of chemical spectral signatures. We report on a combined theoretical and
      experimental study on the benzenethiol on silver and 4-mercaptophenol on silver
      systems. The primary and unique finding was that for the benzenethiol on silver
      system the inclusion of interaction between multiple benzenethiol analyte
      molecules was essential to account for the relative enhancements observed
      experimentally. An examination of the molecular orbitals showed sharing of
      electron density across the entire model of multiple benzenethiol molecules
      mediated by the metal atoms. The addition of multiple 4-mercaptophenol molecules
      to the theoretical model had little effect on the predicted spectra, and we
      attribute this to the fact that a much larger model is necessary to replicate the
      networks of hydrogen bonds. Molecular orientation was also found to affect the
      predicted spectra, and it was found that an upright position improved agreement
      between theoretical and experimental spectra. An analysis of the vibrational
      frequency shifts between the normal Raman spectrum of the neat compound and the
      SERS spectrum also suggests that both benzenethiol and 4-mercaptophenol are in an
      upright position. 

PMID- 23961763
TI  - Prof. Keith Campbell: a personal perspective of a friend and colleague.

PMID- 23961764
TI  - Pluripotent stem cells from maturing oocytes.
AB  - Embryonic stem cells are mostly derived from mature oocytes that were either
      fertilized or activated parthenogenetically and then reached the blastocyst
      stage. From the cell cycle perspective, fertilization or activation induces the
      exit from meiosis, decondensation of oocyte chromosomes, and the entry into
      mitosis. Decondensation of oocyte chromatin with subsequent formation of nuclei
      can be, however, induced at any postgerminal vesicle breakdown meiotic maturation
      stage. In this article, we discuss the possibility of cleavage of transformed
      maturing oocytes and whether they can reach the blastocyst stage, from which
      pluripotent stem cell lines could be derived.

PMID- 23961765
TI  - DNA aneuploidy in porcine bone marrow-derived mesenchymal stem cells undergoing
      osteogenic and adipogenic in vitro differentiation.
AB  - In this study, we estimated the distribution of DNA diploidy and aneuploidy in
      porcine mesenchymal stem cells (pMSCs) that were subjected to
      osteoblast/osteocyte and adipocyte differentiation to determine the impact of
      long-term in vitro culture and differentiation on the cell cycle distribution and
      nuclear DNA profile. This determination could be helpful to confirm or exclude
      the suitability of physico-chemical culture conditions for the purposes of both
      the maintenance of an undifferentiated state and to promote differentiation in
      pMSCs. Flow cytometry was applied to analyze the cell cycle and occurrence of
      aneuploidy/diploidy, and real-time PCR was used to quantify aP2 and osteocalcin,
      markers of adipocytes and osteocytes, respectively. The chi-squared test was used
      to compare the total rates of G0/G1-, S-, and G2/M-phase cell fractions with
      diploid and aneuploid DNA and the DNA index ratios between three experimental
      groups of pMSCs. Five weeks of in vitro culture under differentiating conditions
      resulted in a considerable reduction of DNA stability and a remarkable increase
      in the rate of cells exhibiting an aneuploid DNA stem line; however, a similar
      dependence was not found in the nondifferentiated MSCs. Furthermore, the cell
      fraction rates in each phase of the mitotic cycle and the DNA index (DI) were
      calculated. The results of real-time PCR for aP2 and osteocalcin proved positive
      MSC differentiation toward adipocytes and osteocytes. In terms of the possible
      use of differentiated MSC lines in tissue engineering and regenerative medicine,
      we propose cytokinetic diagnostics using flow cytometry as an objective and
      useful method for screening the tumor-forming capacity and malignancy potential
      of both in vitro long-term cultured MSCs and MSCs subjected to ectopic
      differentiation.

PMID- 23961766
TI  - He was my mentor.

PMID- 23961767
TI  - Alternating current electric fields of varying frequencies: effects on
      proliferation and differentiation of porcine neural progenitor cells.
AB  - Application of sinusoidal electric fields (EFs) has been observed to affect
      cellular processes, including alignment, proliferation, and differentiation. In
      the present study, we applied low-frequency alternating current (AC) EFs to
      porcine neural progenitor cells (pNPCs) and investigated the effects on cell
      patterning, proliferation, and differentiation. pNPCs were grown directly on
      interdigitated electrodes (IDEs) localizing the EFs to a region accessible
      visually for fluorescence-based assays. Cultures of pNPCs were exposed to EFs (1
      V/cm) of 1 Hz, 10 Hz, and 50 Hz for 3, 7, and 14 days and compared to control
      cultures. Immunocytochemistry was performed to evaluate the expression of neural
      markers. pNPCs grew uniformly with no evidence of alignment to the EFs and no
      change in cell numbers when compared with controls. Nestin expression was shown
      in all groups at 3 and 7 days, but not at 14 days. NG2 expression was low in all
      groups. Co-expression of glial fibrillary acidic protein (GFAP) and TUJ1 was
      significantly higher in the cultures exposed to 10- and 50-Hz EFs than the
      controls. In summary, sinusoidal AC EFs via IDEs did not alter the alignment and
      proliferation of pNPCs, but higher frequency stimulation appeared to delay
      differentiation into mature astrocytes.

PMID- 23961769
TI  - Directed nickel-catalyzed negishi cross coupling of alkyl aziridines.
AB  - Herein we report a nickel-catalyzed C-C bond-forming reaction between simple
      alkyl aziridines and organozinc reagents. This method represents the first
      catalytic cross-coupling reaction employing a nonallylic and nonbenzylic Csp(3)-N
      bond as an electrophile. Key to its success is the use of a new N-protecting
      group (cinsyl or Cn) bearing an electron-deficient olefin that directs oxidative
      addition and facilitates reductive elimination. Studies pertinent to elucidation
      of the mechanism of cross coupling are also presented. 

PMID- 23961768
TI  - Imprinted genes and satellite loci are differentially methylated in bovine
      somatic cell nuclear transfer clones.
AB  - In mammals, genome-wide epigenetic reprogramming systems exist in primordial germ
      cells and zygotes. These reprogramming systems play crucial roles in regulating
      genome functions during critical stages of embryonic development, and they confer
      the stability of gene expression during mammalian development. The frequent
      unexpected loss of progeny from somatic cell nuclear transfer (SCNT) is an
      ongoing problem. In this study, we used six cloned bovines (named NT-1 to NT-6),
      which were created by ear fibroblast nuclear transfer and displayed short life
      spans with multiple organ defects, as an experimental model. We focus here on
      three imprinted genes (IGF2, H19, and XIST) and four satellite loci (Satellite I,
      Satellite II, Art2, and VNTR) to investigate their methylation changes. The
      results revealed that aberrant methylation frequently occurred in the analyzed
      imprinted genes, but not in the satellite loci, of the cloned bovines. After the
      bovine fibroblast cells were treated with the 5-aza-2(')-deoxycytidine (5-Aza-dc)
      demethylation agent, the methylation percentages of the XIST and H19 putative
      differentially methylated region (DMR) were significantly decreased (XIST,
      p<0.01; H19, p<0.05) followed by an increase in their mRNA expression levels
      (p<0.01). Furthermore, we found that five short-lived cloned bovines (NT-1 to NT
      5) exhibited more severe aberrant methylation changes in the three imprinted
      genes examined than the little longer-lived clone (NT-6) compared with wild-type
      (WT) cows. Our data suggest that the reprogramming of the methylation-controlled
      regions between the imprinted genes and satellite loci are differences and may be
      involved with additional mechanisms that need further elucidation.

PMID- 23961770
TI  - Pharmacokinetic evaluation of pomalidomide for the treatment of myeloma.
AB  - INTRODUCTION: Multiple myeloma (MM) patients who relapse, or become refractory to
      currently available novel agents, have limited treatment options with poor
      outcomes. The introductions of the newer proteasome inhibitor carfilzomib and the
      immunomodulatory agent pomalidomide have provided new treatment strategies within
      the relapse setting. Pomalidomide, a novel 4-amino derived from thalidomide, was
      recently introduced for the treatment of MM. In addition to being immune-adjuvant
      with anti-inflammatory properties, pomalidomide has shown several biological
      activities that directly and indirectly inhibit MM cells. AREAS COVERED: Herein,
      the authors review the chemistry, the mechanism of action and the pharmacokinetic
      properties of pomalidomide. The data reviewed within this article based on the
      relevant literature pertaining to pomalidomide's Phase I, II and III clinical
      trials. EXPERT OPINION: Pomalidomide has shown to be a safe and active agent,
      both alone and in combination with dexamethasone, in heavily pretreated patients.
      Furthermore, pomalidomide represents an effective treatment option for
      relapsed/refractory patients. Results from the ongoing trials evaluating the
      synergistic activity of pomalidomide combined with conventional chemotherapy or
      novel agents look promising and may prove to be viable treatment options in the
      future.

PMID- 23961771
TI  - Synthesis and evaluation of bifunctional sGC regulators: optimization of a
      connecting linker.
AB  - Hybrid molecules composed of PpIX and cobyrinic acid derivatives conjugated
      through linkers of varying length and composition were prepared via 1,3-dipolar
      cycloaddition (CuAAC) or amidation/esteryfication reactions. They were tested for
      activation of soluble guanylyl cyclase (sGC), a key enzyme in the NO/cGMP
      signaling pathway, by an in vitro GTP->cGMP conversion assay. Using purified heme
      deficient sGC and truncated sGC variants lacking a heme-binding domain, we
      demonstrated that such hybrid molecules may activate sGC by targeting heme
      binding and/or catalytic domain. While all conjugates activated sGC, only
      selected compounds served as bifunctional regulators and were capable of
      simultaneous targeting both heme and catalytic domains of sGC. The length and
      type of a linker connecting both components had a profound effect on the extent
      of sGC activation, indicating that the linker's type is crucial for their binding
      affinities with regulatory and catalytic domains. Only hybrids with the
      conjugated linker of 13-16 atom length synergistically target both domains and
      displayed the lowest EC50 and highest activating potency. Compounds with shorter
      connecting linkers were much less potent and were no more active than the
      cobyrinic acid component alone. The most active conjugate, which showed a 60-fold
      activation of sGC, was compound 11, in which PpIX and cobyrinic acid components
      are separated by 11 atoms chain with the triazole moiety in between. 

PMID- 23961772
TI  - Not all errors are created equally: specific ERN responses for errors originating
      from distractor-based response retrieval.
AB  - The binding of stimulus (S) and response (R) features into S-R episodes or 'event
      files' is a basic process for the regulation of behavior. Recent studies have
      shown that even irrelevant information is bound into event files. Associating
      distractors with responses leads to more efficient behavior if irrelevant and
      relevant stimuli are correlated, but leads to erroneous or inadequate behavior if
      irrelevant stimuli do not predict relevant ones. In this study, we investigated a
      control mechanism that is triggered by errors resulting from distractor-based
      response retrieval. We tested whether the error-related negativity (ERN) differs
      depending on the error source. In particular, we compared errors due to
      distractor-based response retrieval with random errors. Errors originating from
      distractor-based response retrieval elicited a stronger (more negative) ERN than
      did other types of errors, suggesting that the cognitive system responds in a
      unique way to this kind of error. This control mechanism is adaptive because it
      prevents the emergence of inadequate response routines. 

PMID- 23961773
TI  - Intra-individual variability of normal and educable mentally retarded children on
      a coincidence timing task.
AB  - A visual coincidence timing task was used to compare the level of performance
      (constant error) and the intra-individual variability of 100 normal and 100
      educable mentally retarded children. The mean performance of the intellectually
      normal children on this task was significantly superior to that of the retarded
      children, and the intra-individual variability of the latter was significantly
      greater than that of the former. The hypothesis that high intra-individual
      variability and depressed level of performance are closely associated was not
      supported. 

PMID- 23961774
TI  - Effects of s-R compatibility and task difficulty on unimaimual movement time.
AB  - Using a system in which S controlled a cursor on an oscilloscope screen by moving
      a lever, the S-R relationship on either hand could be reversed. This system was
      used in two experiments designed to investigate the effect on unimanual movement
      time of varying S-R compatibility, and task difficulty as defined by Fitts
      (1954). The results indicated the necessity of specifying task difficulty in an
      investigation of S-R compatibility. Further, it was found that as task difficulty
      increased the difference in performance between the right and left hands became
      more marked. 

PMID- 23961775
TI  - The effects of changes in direction, load, and amplitude of movement on gradation
      of effort.
AB  - Gradation of a response is a form of amplification control which determines that
      the response as a whole is appropriately graded in effort. The present study is
      an investigation of the effects of changes in resistance to cranking, amplitude
      of movement, and direction of movement on the gradation of the response in hand
      cranking. Criteria of gradation were derived from strain gauge and EMG records. A
      modification in gradation occurred principally when the resistance to movement
      changed appreciably. The findings are discussed in terms of one basic pattern of
      organization that is used, despite variations in task conditions. 

PMID- 23961776
TI  - Feedback and practice as variables in error detection and correction.
AB  - Adams' (1971) closed-loop theory has response-produced feedback and practice as
      determinants of the internal reference that is the learned basis of error
      detection and correction. Two experiments were conducted on error detection and
      correction in test of this assumption, using a linear displacement task. Amounts
      of feedback and practice were variables, and both were found to be effective in
      error detection and correction. The discussion was mainly in terms of the
      informativeness of feedback channels and what it means for motor behavior. 

PMID- 23961777
TI  - Perceptual Delay of the Second of two Adjacent Stimuli in a Large Body Movement.
AB  - Conscious perception of the apparent time of occurrence of the second of two
      closely spaced stimuli was examined using an' extended movement A considerable
      perceptual delay was found whether or not the response to the second stimulus
      curtailed the primary response. This delay was found whether the second stimulus
      occurred during the movement response to the first stimulus or during the
      reaction time to the first stimulus. At present there appears to be no
      satisfactory explanation of the phenomenon. 

PMID- 23961778
TI  - The relationship among motor tasks for preschool children.
AB  - The relationship among motor tasks on the Whitener Motor Performance Battery of
      Tests was determined. The sample included 208 preschool children from white,
      middle and upper socio-economic class families. Factor analyses revealed
      relationships among the tasks of the Whitener Motor Performance Battery of Tests
      for two age groups. Four factors extracted for the 3-and 4-yr. age group were
      "Total Body Strength and Leg Power," "Arm and Shoulder Power and Gross
      Coordination," "Rhythmic Coordination," and an "Unknown" factor. For the 5-and 6
      yr. age group, five factors were named: "Rhythmic Coordination," "Arm and Total
      Body Strength," "Speed of Movement and Power," "Gross Motor Coordination" and
      "Dynamic Balance." 

PMID- 23961779
TI  - Effects of concurrent negative feedback on performance of two motor tasks.
AB  - The effects of stress on state anxiety and on HR of male high school Ss were
      investigated using two psychomotor tasks. In the Stress Condition, Ss received
      negative feedback about performance; Ss in the Nonstress Condition were given
      rest intervals. Ss in the two conditions showed similar pretask, p> .05, A-State
      and HR measures. However, during the tasks the groups showed differing regression
      lines. The Nonstress Group maintained the same A-State level across the tasks
      with increased HR occurring as a result of the motor task. The Stress Group
      increased in A-State and HR measures. The two groups were significantly
      different, p<.01, in all within-task measures. The Stress Group performed better
      on the two motor skill tasks. 

PMID- 23961780
TI  - Retention characteristics of motor short-term memory cues.
AB  - The retention characteristics of several cues thought to underlie movement
      reproduction ability were examined and the results were discussed in terms of two
      models of motor short-term memory (Laabs, 1973; Pepper & Herman, 1970). Trace
      decay was indexed by constant error and not variable error. It appeared that the
      movement cues studied all had access to the central processing capacity in that
      forgetting did not occur until rehearsal was blocked by the introduction of a
      secondary task. However, there was some evidence to indicate that different cues
      are centrally represented in varying degrees of exactness. In this respect
      reliance on active movement cues and location cues produced better reproduction
      than passive movement and distance cues, respectively. The existence of an
      adaptation level established from the range of movement utilized was supported,
      and short movements were more dependent on central processing capacity than were
      long movements. 

PMID- 23961781
TI  - Validation of Italian version of Brace Questionnaire (BrQ).
AB  - BACKGROUND: Brace questionnaire (BrQ) is a tool used to evaluate Health Quality
      of Life (HRQoL) in patients with Adolescent Idiopathic Scoliosis (AIS) that
      undergo bracing treatment. The BrQ has not been translated and validated for
      Italian-speaking patients with AIS. The aim of the study was to perform a trans
      cultural validation of BrQ to be used in an Italian speaking population. METHODS:
      Translation into Italian (I-BrQ) and back translation to the original Greek (G
      BrQ) was performed. The final I-BrQ was then analyzed for Italian cultural
      characteristics and no inconsistencies were found. After that, construct validity
      was measured analyzing the I-BrQ relationship with 1) Scoliosis Research Society
      22 patient Questionnaire (SRS-22), in order to evaluate the relationship with
      another patient-oriented questionnaire not focused on brace therapy; 2) Cobb
      degree scale, in order to evaluate the relationship with the magnitude of the
      curve. Reproducibility was also tested. RESULTS: Translation of the G-BrQ into
      Italian was successful and back-translation to Greek corresponded well with the
      original Greek version.Global I-BrQ correlated strongly with SRS-22 (r = 0.826; p
      < 0.001). Almost all sub scores from each I-BrQ domain strongly correlated with
      the single domain scores of SRS-22. Only two I-BrQ sub scores weakly inversely
      correlated with Cobb degree value.Reproducibility was good (Spearman-Brown
      coefficient value was 0.943; p < 0.05). CONCLUSIONS: Trans-cultural validation in
      Italian language showed the validity and reliability of the I-BrQ.

PMID- 23961782
TI  - An audit of sample sizes for pilot and feasibility trials being undertaken in the
      United Kingdom registered in the United Kingdom Clinical Research Network
      database.
AB  - BACKGROUND: There is little published guidance as to the sample size required for
      a pilot or feasibility trial despite the fact that a sample size justification is
      a key element in the design of a trial. A sample size justification should give
      the minimum number of participants needed in order to meet the objectives of the
      trial. This paper seeks to describe the target sample sizes set for pilot and
      feasibility randomised controlled trials, currently running within the United
      Kingdom. METHODS: Data were gathered from the United Kingdom Clinical Research
      Network (UKCRN) database using the search terms 'pilot' and 'feasibility'. From
      this search 513 studies were assessed for eligibility of which 79 met the
      inclusion criteria. Where the data summary on the UKCRN Database was incomplete,
      data were also gathered from: the International Standardised Randomised
      Controlled Trial Number (ISRCTN) register; the clinicaltrials.gov website and the
      website of the funders. For 62 of the trials, it was necessary to contact members
      of the research team by email to ensure completeness. RESULTS: Of the 79 trials
      analysed, 50 (63.3%) were labelled as pilot trials, 25 (31.6%) feasibility and 14
      were described as both pilot and feasibility trials. The majority had two arms (n
      = 68, 86.1%) and the two most common endpoints were continuous (n = 45, 57.0%)
      and dichotomous (n = 31, 39.2%). Pilot trials were found to have a smaller sample
      size per arm (median = 30, range = 8 to 114 participants) than feasibility trials
      (median = 36, range = 10 to 300 participants). By type of endpoint, across
      feasibility and pilot trials, the median sample size per arm was 36 (range = 10
      to 300 participants) for trials with a dichotomous endpoint and 30 (range = 8 to
      114 participants) for trials with a continuous endpoint. Publicly funded pilot
      trials appear to be larger than industry funded pilot trials: median sample sizes
      of 33 (range = 15 to 114 participants) and 25 (range = 8 to 100 participants)
      respectively. CONCLUSION: All studies should have a sample size justification.
      Not all studies however need to have a sample size calculation. For pilot and
      feasibility trials, while a sample size justification is important, a formal
      sample size calculation may not be appropriate. The results in this paper
      describe the observed sample sizes in feasibility and pilot randomised controlled
      trials on the UKCRN Database.

PMID- 23961783
TI  - Possible association of hepatitis C virus infection with late-onset psoriasis: a
      hospital-based observational study.
AB  - Psoriasis is a chronic inflammatory disease mainly involving the skin and joints,
      mediated by pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha. In
      hepatitis C, continuous inflammation mediated by TNF-alpha leads to liver
      cirrhosis and diabetes mellitus. Hence, psoriasis and hepatitis C have
      pathophysiological factors in common. An epidemiological association between the
      two conditions has been reported, but no detailed research has yet been
      performed. Frequency of hepatitis C virus (HCV) infection was assessed in 717
      patients with psoriasis and 38 057 with all other dermatological diseases who
      visited Fukuoka University Hospital in 1998-2011. HCV+ and HCV- psoriatic
      patients were further compared. Frequency of HCV infection was significantly
      higher in psoriasis (7.5%) than in controls (3.3%) in overall ages. When
      stratified by age at the first visit, the frequency was significantly higher in
      patients with psoriasis than in controls aged in their 60s (11.8% vs 6.6%,
      respectively, P = 0.0215) and 70s (19.5% vs 7.3%, P < 0.0001). HCV+ psoriatic
      patients were significantly older at onset than HCV- ones (median, 54 vs 39
      years), stronger male predominance (male/female ratio, 4.4:1), similar family
      history of psoriasis, higher association of diabetes mellitus and hypertension,
      and significantly lower body mass index (22.4 +/- 2.73 vs 24.2 +/- 4.61), in age
      stratified (>= 40 years) analysis. HCV+ psoriatic patients were less obese, but
      still had a higher frequency of diabetes mellitus and hypertension, possibly due
      to chronic inflammation in the liver and other organs. HCV infection may trigger
      psoriasis, especially late-onset psoriasis, possibly via overproduction of TNF
      alpha, a common mediator of the two conditions.

PMID- 23961784
TI  - Serum Fetuin-A levels, insulin resistance and oxidative stress in women with
      polycystic ovary syndrome.
AB  - This study was designed to determine serum Fetuin-A levels and establish whether
      serum Fetuin-A level is related with insulin resistance, oxidative stress,
      ovarian hyperandrogenism and dyslipidemia in women with polycystic ovary syndrome
      (PCOS). Twenty-two patients with PCOS and twenty-one healthy control women were
      evaluated in this controlled clinical study. Serum Fetuin-A, lipid fractions,
      glucose, insulin, malondialdehyde (MDA), myeloperoxidase (MPO), glutathione
      (GSH), superoxide dismutase (SOD) and other hormone (gonadotropins, androgens)
      levels were measured. The estimate of insulin resistance was calculated by
      homeostasis model assessment (HOMA-R). The women with PCOS had significantly
      higher serum fasting glucose, insulin, luteinizing hormone (LH), MDA, Fetuin-A
      levels, and LH/follicle-stimulating hormone (FSH) ratio, free androgen index
      (FAI), HOMA-IR than healthy women. However, sex hormone-binding globulin (SHBG)
      and GSH levels were significantly lower in patients with PCOS compared with
      controls. Fetuin-A was positively correlated with insulin, HOMA-IR and FAI.
      Multiple regression analysis revealed that FAI was strong predictor of serum
      Fetuin-A level. Serum Fetuin-A level was related with insulin resistance and
      ovarian hyperandrogenism in women with PCOS. These results suggest that Fetuin-A
      may have a role in triggering the processes leading to insulin resistance and
      androgen excess in PCOS.

PMID- 23961785
TI  - The ageing of the nursing workforce: what lies ahead and what we can do.

PMID- 23961786
TI  - In the footsteps of nurse editors and scholars: ideas, information and
      inspiration.

PMID- 23961787
TI  - We must take a critical look at nursing education.

PMID- 23961788
TI  - Having an impact on global health: the power of one, the power of many.

PMID- 23961790
TI  - Collaboration between hospital physicians and nurses: an integrated literature
      review.
AB  - BACKGROUND: Ineffective physician-nurse collaboration has been shown to cause
      work dissatisfaction among physicians and nurses and compromised the quality of
      patient care. AIM: The review sought to explore: (1) attitudes of physicians and
      nurses toward physician-nurse collaboration; (2) factors affecting physician
      nurse collaboration; and (3) strategies to improve physician-nurse collaboration.
      METHODS: A literature search was conducted in the following databases: CINAHL,
      PubMed, Wiley Online Library and Scopus from year 2002 to 2012, to include papers
      that reported studies on physician-nurse collaboration in the hospital setting.
      FINDINGS: Seventeen papers were included in this review. Three of the reviewed
      articles were qualitative studies and the other 14 were quantitative studies.
      Three key themes emerged from this review: (1) attitudes towards physician-nurse
      collaboration, where physicians viewed physician-nurse collaboration as less
      important than nurses but rated the quality of collaboration higher than nurses;
      (2) factors affecting physician-nurse collaboration, including communication,
      respect and trust, unequal power, understanding professional roles, and task
      prioritizing; and (3) improvement strategies for physician-nurse collaboration,
      involving inter-professional education and interdisciplinary ward rounds.
      CONCLUSION: This review has highlighted important aspects of physician-nurse
      collaboration that could be addressed by future research studies. These include:
      developing a comprehensive instrument to assess collaboration in greater depth;
      conducting rigorous intervention studies to evaluate the effectiveness of
      improvement strategies for physician-nurse collaboration; and examining the role
      of senior physicians and nurses in facilitating collaboration among junior
      physicians and nurses. Other implications include inter-professional education to
      empower nurses in making clinical decisions and putting in place policies to
      resolve workplace issues.

PMID- 23961791
TI  - Defining nurse regulation and regulatory body performance: a policy Delphi study.
AB  - CONTEXT: Professional self-regulation is a privilege and needs to deliver against
      the underpinning social contract between the professional and citizens who are
      receiving care and services. AIMS: The aims of this study were to generate,
      international consensus on a contemporary definition of professional nurse
      regulation; and to articulate the key features of a highly performing regulatory
      body, and postulate which regulatory model and administrative arrangements are
      best suited to attain the key features. METHOD: A highly diverse and globally
      recruited random stratified sample of 75 experts was approached to participate in
      a classic three-round policy Delphi study. Quantitative and qualitative data were
      generated and subjected to thematic and statistical analysis. Both non-parametric
      and descriptive statistical techniques were used in relation to quantitative
      data. RESULTS: Consensus on a revision of the current International Council of
      Nurses definition of professional nurse regulation was developed and a set of 47
      key features of high-performing regulatory bodies was agreed. Although a strong
      preference for the delegated self-regulatory model (43%) and single-board
      administrative approach (48%) was expressed the underlying rationale for such a
      preference was unclear. CONCLUSION: The research makes an important contribution
      to an underdeveloped field of study. The case for conducting more quantitative
      investigations to ascertain the best regulatory model and associated
      administrative approach has been made.

PMID- 23961792
TI  - Nurses' preferred end-of-life treatment choices in five countries.
AB  - BACKGROUND: Previous research has focused on physician's perspectives of end-of
      life (EOL) decision making as well as patient and family EOL decision making.
      There is a lack of research pertaining to the EOL treatment preferences of nurses
      and especially nurses working in a variety of care settings. AIM: The aim of this
      study was to compare nurses' EOL treatment preferences in Hong Kong, Ireland,
      Israel, Italy and the USA. METHODS: A comparative descriptive design was used
      with a convenience sample of nurses (n = 1089). A survey questionnaire using EOL
      hypothetical clinical case scenarios was used to collect data between June 2011
      and July 2012. RESULTS: Nurses in every country consistently chose a more
      aggressive option for patients than for themselves or for a parent. The treatment
      preferences of nurses varied from country to country. Lack of knowledge of
      patients' wishes and duty of care were the main influencing factors on treatment
      preferences. STUDY LIMITATIONS: The study was limited to the hypothetical nature
      of the scenarios; however, the study highlights numerous future research
      questions. CONCLUSIONS: This study is the first to examine and compare nurses'
      preferred EOL treatment choices in five countries from three different
      continents. The findings of this study raise several important questions for
      healthcare researchers, for policy development, and highlight the need for
      further international collaboration.

PMID- 23961793
TI  - Nurses' perceptions about health sector privatization in Turkey.
AB  - AIM: The aim of this study is to identify the perceptions of the nurses about the
      privatization implementation, as it pertains to privatization, health services
      privatization and the impact of privatization on nursing in Turkey. BACKGROUND:
      Turkey is taking important steps in health services privatization but the related
      choices made in political arena are not shared with the employees of the health
      institutions where the privatization implementations are to take place. METHODS:
      The study was conducted among nurses who are working for the state health
      institutions and the members of professional organizations of healthcare workers,
      which are operating in Istanbul in Turkey. Data were collected via Nurses'
      Privatization Perception Scale in 2009 and were analysed using mean calculations,
      analysis of variance, Mann-Whitney U-test, t-test, Kruskal-Wallis test and
      Cronbach's alpha analyses. FINDINGS: Nurses' perceptions of privatization in
      general, health services privatization and the impact of privatization on nursing
      were found to be negative in all of the three sub-domains of the scale, as well
      as their perceptions of privatization implementations measured throughout the
      scale. The conducted comparisons showed that nurses' perceptions of the
      privatization implementations varied in accordance with independent variables.
      CONCLUSIONS: The privatization implementations put in place in health services
      are perceived negatively by nurses. Policy makers in relevant fields are
      recommended to take the findings of this study into consideration.

PMID- 23961794
TI  - Evaluation of registered nurses' knowledge and practice of documentation at a
      Jamaican hospital.
AB  - BACKGROUND: Documentation is central to the management of patients in hospitals.
      Nurses are trained to follow the Ministry of Health Jamaica's policy on
      documentation, which is available in all public hospitals. AIM: Audit of
      documentation practices by registered nurses at a referral hospital. METHODS:
      Ninety patient records from three medical wards were audited for documentation
      practices using an approved Jamaican Ministry of Health tool. Qualitative data
      regarding the nurses' experience with documentation were gathered from a focus
      group discussion of 12 nurses assigned to the audited wards. FINDINGS: Most
      nurses (98%) followed documentation guidelines for admission by recording
      patients' past complaints, medical history and assessment data; used authorized
      abbreviations only (97%); documented nursing actions taken after identification
      of a problem and a provided a summary of the patients' condition at the end of
      the shift (98%). However, only 26% of the records had nursing diagnosis, which
      corresponded to the current medical diagnosis and 48% had documented evidence of
      discharge planning. Eighty-seven per cent had no evidence of patient teaching.
      The main reported factors affecting documentation practices were workload and
      staff/patient ratios. Participants believed that nursing documentation could be
      improved with better staffing, improved peer guidance and continuing education.
      CONCLUSIONS: The study showed high levels of accurate documentation by nurses at
      a referral hospital in Western Jamaica and the nurses appeared to be familiar
      with the required documentation guidelines with policy manuals available on each
      ward. Weaknesses in discharged planning and patient teaching were identified,
      which should be addressed by targeted continuing nursing.

PMID- 23961795
TI  - Patterns and predictors of non-use of family planning methods in Ethiopian women:
      a panel survey.
AB  - PURPOSE: Family planning (FP) is a key global health issue for achieving
      millennium development goals by 2015. The aim of this study was to identify
      predictors of changes in FP practice before and after interventions among
      Ethiopian women of reproductive age in a rural area. METHODS: This study used a
      panel survey to identify predictors that placed women at greater risk for non-use
      of FP methods. The sample consisted of 407 women aged 19-49 years old living in a
      rural community of Ethiopia who completed both a baseline and follow-up survey.
      Trained local enumerators conducted face-to-face interviews during home visits.
      Patterns of FP practice were categorized into four groups: FP use at both
      baseline and follow-up; use at baseline but non-use at follow-up; non-use at
      baseline but use at follow-up; non-use at both baseline and follow-up. Logistic
      regression and classification and regression tree analyses were used. RESULTS: In
      a binary logistic regression, women over 35 years old with a negative attitude
      towards FP and resided in the Sibu area were less likely to start FP practice.
      Women over 35 years who were in poor health and resided in Sibu were less likely
      to continue FP practice. For the decision tree, age was the primary node for FP
      non-users at baseline while area of residence was the primary node for FP users
      at baseline. CONCLUSION: Age, health status, attitude towards FP, and area of
      residence are the primary considerations when developing FP interventions for
      Ethiopian women in a resource-limited rural area.

PMID- 23961796
TI  - Support needs of caregivers: case studies in South Africa.
AB  - BACKGROUND: Limpopo is one of the poorest provinces in South Africa with limited
      resources to support caregivers and individuals who are learning disabled.
      Offering support and care to children with learning disabilities can be a complex
      and difficult task to achieve. Caregivers carry great responsibility for ensuring
      the needs of children in their care are met. Such responsibility can generate
      great amounts of stress that may negatively impact caregivers' day-to-day
      functioning. Yet, research concerning how to support caregivers in meeting the
      needs of this group of children in Limpopo has never before been carried out.
      AIM: To investigate the support needs of caregivers caring for children with
      learning disabilities. METHODS: A case study design of three families of children
      with learning disabilities was used. Data were generated in two phases using a
      semi-structured interview format. In phase 1, participants were interviewed in
      their homes. Phase 2 relates to follow-up interviews of participants in a
      community clinic. All data were analysed using Interpretative Phenomenological
      Analysis. FINDINGS: The study identified a range of support needs for caregivers.
      Examples of these include financial, emotional, practical support, training,
      respite care, affiliate stigma and partnership working. DISCUSSION: Caring for
      children with learning disabilities was perceived as difficult and frustrating,
      yet rewarding. This difficulty was noted to be compounded by caregivers' lack of
      skills and knowledge of caring for these children. They also had experiences of
      stigma, which sometimes involves overt acts of discrimination and social
      exclusion that further added to their frustration. CONCLUSIONS: The study
      findings have implications for practice and policy. Regular training and support
      should be offered to caregivers in order to broaden their understanding of
      learning disabilities and enhance their caring ability. Nurses are the main
      source of training and support and offer these during clinic-based engagement and
      home visits.

PMID- 23961797
TI  - Screening for breast cancer among young Jordanian women: ambiguity and
      apprehension.
AB  - AIMS: The goal of this study was to understand young Jordanian women's attitudes
      towards breast cancer screening practices in order to improve young women's
      uptake of screening and early detection. BACKGROUND: The incidence of breast
      cancer is increasing annually among younger Jordanian women; however, little is
      known about their attitudes towards breast cancer and associated screening
      practices. Young women's attitudes towards breast cancer must be taken into
      account when designing screening strategies and interventions specifically for
      this age group. Screening strategies must also acknowledge young women's cultural
      context; however, little is known about how culture shapes their understandings
      and practices. METHODS: A qualitative interpretive approach was utilized to
      interview 45 young educated women about their breast cancer views and screening
      practices. Data were analysed thematically. FINDINGS AND DISCUSSION: Four
      overlapping themes emerged: (i) young women should not think about it, (ii)
      absence of a role model, (iii) cultural shame of breast cancer, and (iv) cancer
      means death and disability. The study found high levels of apprehension and
      ambiguity related to breast cancer. This was associated with the perceived impact
      of a cancer diagnosis on a young woman's social status and family role. Family
      support was perceived to be a necessary prerequisite for seeking treatment or
      screening. CONCLUSIONS: Understanding young women's perception about screening
      and early detection of breast cancer is essential for policy makers and
      healthcare providers to design culturally appropriate and age-appropriate health
      promotion campaigns and services.

PMID- 23961798
TI  - Motives for self-harm: views of nurses in a secure unit.
AB  - BACKGROUND: Self-harm is a widespread behaviour among people with mental health
      problems. Although guidance on how to manage self-harm is offered, it is still a
      behaviour that is misunderstood by many nurses. Such misunderstanding is
      generally attributed to the perceived motives for self-harm and lack of
      specialized education to manage the behaviour. As a consequence, the care
      provided is usually inadequate and inappropriate. Yet, research concerning
      nurses' reasons of users' self-harming behaviours is limited. AIM: This paper
      reports on a study that explores nurses' explanations of the motives for self
      harm in a secure adolescent unit in England. METHODS: The study utilized a
      phenomenological methodology with semi-structured individual interviews (n = 25).
      The data were analysed thematically using interpretative phenomenological
      analysis. RESULTS: The findings indicate that the behaviour of self-harm has
      multiple motives. Examples of these include affect regulation, coping with
      distress, averting death, regaining control and attention seeking. DISCUSSION:
      Self-harm is a complex behaviour commonly experienced in secure environments.
      Nurses assume that users who self-harm are motivated by a desire to seek
      attention and manipulate others. Users may find these beliefs humiliating. Such
      feelings may increase users' risks for further self-harm. Most adolescents who
      self-harm experience unbearable emotions because of their past sexual abusive
      encounters. They self-harm to regulate these emotions. These affect regulatory
      functions may act as reinforcers of self-harming behaviours. CONCLUSIONS:
      Improved understanding of self-harm and its motives may result in improved nurse
      user relationships and thus safer and more effective care provision.

PMID- 23961799
TI  - HIV knowledge and condom intention among sexually abstinent Chinese students.
AB  - AIMS: To (a) assess the HIV/AIDS knowledge and sources of HIV/sexually
      transmitted infection (STI) information among sexually abstinent college students
      in China; (b) examine whether constructs from the transtheoretical model (TTM)
      are applicable to this study population regarding condom use intention; and (c)
      evaluate the association between genders and TTM constructs, and HIV/AIDS
      knowledge. BACKGROUND: Chinese college students are vulnerable to HIV and other
      STIs. Strategies targeting abstinent students are more cost-effective than
      providing treatment for diseases. METHODS: We surveyed 390 students enrolled in
      two universities in China. Data were collected from June 2009 to March 2010.
      RESULTS: Only 11% and 24% were aware of HIV spread by infected semen and of the
      protective effects of condom use against HIV. The mass media were major sources
      of HIV/STI information. Individuals who had higher levels of self-efficacy and
      reported more perceived benefits and fewer perceived barriers were more likely to
      be in TTM contemplation stage of condom use than those in precontemplation.
      Females were less likely to discuss HIV/STIs through online chat or email with
      strangers than males. Individuals who had higher levels of self-efficacy and
      reported more perceived benefits and fewer perceived barriers were more likely to
      be in TTM contemplation stage of condom use than those in precontemplation.
      CONCLUSION: Sexually abstinent college students in China may be more likely to
      transition from precontemplation to contemplation if they know the benefits of
      condom use for the prevention of HIV/STIs and if they learn to successfully
      minimize potential barriers related to condom use.

PMID- 23961800
TI  - Health promotion practice and its implementation in Swedish health care.
AB  - INTRODUCTION: Health promotion practice is an important work assignment within
      the entire health and medical care sector. Nurses are important for the
      development and implementation of health promotion in clinical practice. AIM: The
      aim was to describe how district nurses view health promotion practice and how it
      was implemented in clinical practice following a training initiative. DESIGN: The
      study has a descriptive design and a qualitative method. METHODS: The sample
      consisted of three focus groups with 16 participants. The interviews were
      conducted as a conversation with focus on the district nurses view of health
      promotion and its implementation in clinical practice. The data have been
      processed using manifest qualitative content analysis. RESULTS: Three categories,
      titled Training as motivation, Lack of grounding and Lack of scope were
      identified. The result demonstrated that training provides motivation, but also
      the importance of grounding in the organization and the need for scope in
      performing health promotion practice. DISCUSSION: Our results show that the
      training initiative has contributed positively to the district nurses' view of
      health promotion practice, but that they also feel that there are obstacles. The
      district nurses in our study suggest that health promotion practice should be
      more visible, and not something that is done when time permits. CONCLUSION: The
      district nurses feel motivated and have an enthusiasm for health promotion
      practice but more time and resources are required to design successful health
      promoting initiatives. Before implementing a major training initiative for
      healthcare personnel in health promotion, it is essential to examine whether the
      conditions for this exist in the organization.

PMID- 23961801
TI  - Using a knowledge utilization framework to explore how findings from one study
      can be applied to other nursing contexts.
AB  - AIM: To discuss the complexities of moving research into practice and through a
      case example, explore how empirical findings from one specific study could be
      applied to nursing in other contexts. BACKGROUND: The processes of moving
      research findings into practice are complex and multidimensional. In this paper,
      an innovative approach to social support, network-focused nursing (NFN), is used
      as a case example to illustrate these complexities. Social support is associated
      with better recovery and survival after illness and based on this, a NFN
      programme was developed in a Danish oncology youth unit. Subsequently, a research
      study was undertaken to investigate the programme and based on the findings, the
      concept NFN was developed. METHODS: A knowledge utilization framework is used to
      explore how empirical findings from the NFN study could be applied to nursing
      more generally. Aligned with this, the specific considerations for implementing
      NFN are explicated. DISCUSSION: Strong leadership, education, management support
      and effective communication are critical factors for research utilization. Moving
      research into practice requires openness to new ideas. Nursing and healthcare
      policies therefore need to support environments in which creativity and
      innovation can flourish. NFN was developed in teenager and young adult cancer
      care, but its principles may be transferable to other clinical environments.
      CONCLUSIONS: It is important that nurse managers and policy makers ensure that
      support and education are available to nurses to facilitate moving research into
      practice. Moreover, resources need to be considered, particularly in countries
      where financial and organizational infrastructures may be weak.

PMID- 23961802
TI  - Validation of the Staff Attitudes to Nutritional Nursing Care Geriatric scale in
      Italian.
AB  - AIM: To validate the Staff Attitudes to Nutritional Nursing Care Geriatric scale
      in Italian, a tool created in Sweden to measure nurses' attitudes towards
      nutritional care in older people. BACKGROUND: Malnutrition in institutionalized
      older people is a serious problem having negative impact on patient outcomes. It
      is reported in the literature that nurses have negative attitudes towards
      nutritional care. METHODS: Forward and back-translation were carried out to build
      the Italian version of the tool. Content and face validity were then examined by
      pilot study. Test-retest reliability with Spearman's rho (rs) correlation,
      intraclass correlation (ICC) and internal consistency reliability with Cronbach's
      alpha were assessed. Differences between test-rest were assessed by t-test.
      RESULTS: Linguistic and semantic adaptation of the tool into Italian was
      successful. Thirty-three nurses skilled in caring for older patients did pilot
      testing and 46 test-retesting. SANN-G GITA-scale achieved good content and face
      validity, good internal consistency reliability (Cronbach's alpha = 0.85) and
      acceptable stability [rs = 0.75, P = 0.001; ICC = 0.76, 95% confidence interval
      (CI) 0.63-0.86; P = 0.001]. The t-test showed no significant difference between
      test and retest results, confirming stability of the tool (t(64) = -0.98; P =
      0.33). DISCUSSION: The process of adaptation of the scale from Swedish to Italian
      language was successful. Thus, the SANN-GITA scale can be useful to assess
      attitudes of nursing staff to nutritional care in the Italian context.
      CONCLUSIONS: This tool will allow the identification of areas where Italian
      nurses have negative attitudes and where to implement strategies to improve
      overall nutritional care.

PMID- 23961803
TI  - The experiences of internationally educated nurses in the southeastern United
      States of America.
AB  - BACKGROUND: US healthcare facilities have addressed nursing shortages in part by
      recruiting internationally educated nurses (IENs), and studies suggest IENs may
      make up a significant percentage of the nursing workforce in urban hospitals.
      Despite the economic recession of 2008-2012, international nurse migration is
      expected to continue. Little is known about IENs in the southeastern USA, and no
      studies have compared their perspectives to those of their US counterparts.
      OBJECTIVE: The purpose of this study was to gain a deeper understanding about the
      experiences of IENs compared to those of US registered nurses (RNs) practising in
      two urban hospitals in southeastern USA. METHODS: This study involved two rounds
      of semi-structured interviews of 82 IENs and US RNs. Interviews focused on themes
      relating to education, barriers to practice, intent to stay in nursing and IENs'
      migration experiences. FINDINGS AND DISCUSSION: Most IENs interviewed migrated to
      the USA after 1990 to join their family and do not plan to return to their home
      countries to practise. Most IENs initially received their Associate Degree in
      Nursing; many have obtained their Bachelor of Science in Nursing degree. IENs and
      newly licensed US RNs faced similar barriers when they began practising in the
      USA, but IENs faced additional challenges adjusting to the attitudes of US
      patients, the perceived lack of respect for nurses and delivering total patient
      care. CONCLUSIONS: IENs would benefit from orientation regarding the cultural
      differences in the USA. In other ways, their challenges are similar to those of
      US RNs; policies regarding education, recruitment and retention could target both
      groups together.

PMID- 23961804
TI  - An analysis of the factors affecting the transition period to professional roles
      for newly graduated nurses in Turkey.
AB  - BACKGROUND: For the majority of newly graduated nurses, the transition to
      professional roles in their lives may be stressful. Common reasons for this
      include feelings of insufficiency with regard to clinical skills, fears of making
      mistakes, increased responsibilities and insufficient guidance. AIM: To identify
      the factors affecting the transition period of newly graduated nurses. METHODS:
      This study was designed and carried out as a descriptive and a cross-sectional
      study of three cohorts of newly graduated students. The study was implemented at
      a military education and research hospital in Ankara, Turkey. The population
      consisted of 234 (89%) of newly graduated nurses. For evaluating data, the SPSS
      15.0 program was used. The paired samples t-test and the Mann-Whitney U-test were
      employed to compare the participants' perceptions about the transition period
      based on certain variables. RESULTS: It is found that 54.7% of nurses surveyed
      have the intent to quit the profession. More than half of the participants stated
      that their expectations were met through working with a preceptor nurse (58.73%).
      Furthermore, almost half of the newly graduated nurses experienced and expressed
      disappointment in the first year of their professional lives. CONCLUSIONS: The
      findings indicate that newly graduated nurses experience some difficulty during
      this period of transition, but assistance from experienced nurses facilitates the
      transition period. IMPLICATIONS FOR NURSING PRACTICE AND RESEARCH: In order to
      increase work quality and satisfaction levels of new graduates, support programs
      must be initialized and their effectiveness must be evaluated regularly by
      clinical administrators and educators.

PMID- 23961806
TI  - Stress echocardiography: safety and tolerability.
AB  - BACKGROUND: Stress echocardiography is a valuable tool for the noninvasive
      diagnosis of ischemic heart disease. Despite its widely use in the clinical
      practice, safety and side effects profile have never been evaluated in Moroccans.
      THE AIM: To assess the safety and tolerability of the two stress echo modalities
      in Moroccans. METHODS: The study was made by 311 patients with known or suspected
      coronary artery disease, 203 underwent exercise echocardiography and 108
      underwent dobutamine echocardiography, major and minor rhythmic complications and
      side effects were recorded for the two groups. RESULTS: We registered 3 (2, 8%)
      major rhythmic events in the dobutamine group (2 sustained supraventricular
      tachycardia and 1 sustained ventricular tachycardia), there was no major rhythmic
      events in the exercise group. Minor rhythmic events were frequent (43, 5% in the
      dobutamine group and 19, 2% in the exercise group with a p = 0, 0001). Severe
      hypotension occurs in 4 (3, 7%) patients during a dobutamine stress, there was no
      significant drop in the blood pressure during exercise stress procedures. Non
      cardiac side effects were more common among patients who underwent a dobutamine
      stress echo (13, 9% vs. 3, 4% with p = 0,001). CONCLUSION: Exercise is safer than
      dobutamine stress echocardiography, complications and adverse effects with the
      use of dobutamine are usually minor and self-limiting.

PMID- 23961807
TI  - Hypercalcaemia: an unusual presenting feature of childhood acute lymphoblastic
      leukaemia.

PMID- 23961805
TI  - MtZR1, a PRAF protein, is involved in the development of roots and symbiotic root
      nodules in Medicago truncatula.
AB  - PRAF proteins are present in all plants, but their functions remain unclear. We
      investigated the role of one member of the PRAF family, MtZR1, on the development
      of roots and nitrogen-fixing nodules in Medicago truncatula. We found that MtZR1
      was expressed in all M. truncatula organs. Spatiotemporal analysis showed that
      MtZR1 expression in M. truncatula roots was mostly limited to the root meristem
      and the vascular bundles of mature nodules. MtZR1 expression in root nodules was
      down-regulated in response to various abiotic stresses known to affect nitrogen
      fixation efficiency. The down-regulation of MtZR1 expression by RNA interference
      in transgenic roots decreased root growth and impaired nodule development and
      function. MtZR1 overexpression resulted in longer roots and significant changes
      to nodule development. Our data thus indicate that MtZR1 is involved in the
      development of roots and nodules. To our knowledge, this work provides the first
      in vivo experimental evidence of a biological role for a typical PRAF protein in
      plants. 

PMID- 23961809
TI  - Solvent-dependent two-photon photoluminescence and excitation dynamics of gold
      nanorods.
AB  - PEG-SH-capped gold nanorods (Au NRs) well dispersed in various organic solvents
      have been prepared to study the solvent effects on the two-photon
      photoluminescence (TPPL) properties and ultrafast excitation dynamics of Au NRs.
      The TPPL intensities of Au NRs in different organic solvents including DMF, DEG,
      CH3OH, C2H5OH, CH3CN, DMSO, and THF were found to be significantly quenched
      compared to that of Au NRs in H2O. Ultrafast time-resolved transient absorption
      and pump-probe measurements have been performed on Au NRs in H2O, DMF, and DEG to
      understand the corresponding quenching mechanisms. Different from the excitation
      decay behaviors of Au NRs in H2O, an additional transient species was observed in
      Au NRs in DMF or DEG upon photoexcitation. This intermediate state is ascribed to
      the charge-separated species, which serves as direct evidence to support that the
      observed TPPL quenching in various organic solvents is due to electron transfer
      from electron-donating solvents to the excited Au NRs. The charge-transfer
      mechanism was further supported by the observation that the TPPL intensity of Au
      NRs in H2O was found to be quenched by nearly 5.0-fold in the presence of S(2-).
      These studies provide useful information on fundamental understanding of the TPPL
      properties as well as development of various potential biological applications of
      gold nanoparticles. 

PMID- 23961808
TI  - Disrupting the CXCL12/CXCR4 axis disturbs the characteristics of glioblastoma
      stem-like cells of rat RG2 glioblastoma.
AB  - BACKGROUND: Glioblastoma stem-like cells (GSC) have been shown to promote tumor
      growth, tumor-associated neovascularization, therapeutic resistance, and
      metastasis. CXCR4 receptors have been found involved in the proliferation,
      metastasis, angiogenesis, and drug-resistant characteristics of glioblastoma.
      However, the role of CXCR4 in modulating the stem-like cell properties of rat
      glioblastoma remains ambiguous. METHODS: To explore the role of the CXCL12/CXCR4
      axis in maintaining rat GSC properties, we disrupted the CXCR4 signaling by using
      small hairpin interfering RNA (shRNA). To investigate the role of the
      CXCL12/CXCR4 axis in maintaining rat GSC properties, we used a spheroid formation
      assay to assess the stem cell self-renewal properties. A western blot analysis
      and PCR arrays were used to examine the genes involved in proliferation, self
      renewal, and cancer drug resistance. Finally, DNA content and flow cytometry, an
      immunohistochemical analysis, and methylcellulose colony formation, in vitro
      invasive and intracranial injection xenograft assays were employed to examine the
      disruptive effect of CXCR4 on the characteristics of GSCs of the RG2 cell line.
      RESULTS: Disrupting CXCR4 inhibited the proliferation of RG2 cells both in vitro
      and in vivo. The spheroid formation assay indicated that CXCR4 was vital for the
      self-renewal of RG2 GSCs. Disrupting the CXCL12/CXCR4 pathway also reduced the
      expression of GSC cell markers, including Nestin, ABCG2, and musashi (Msi), and
      the expression of genes involved in regulating stem cell properties, including
      Oct4, Nanog, maternal embryonic leucine zipper kinase (MELK), MGMT, VEGF, MMP2,
      and MMP9. CONCLUSION: The chemokine receptor CXCR4 is crucial for maintaining the
      self-renewal, proliferation, therapeutic resistance, and angiogenesis of GSCs of
      rat RG2 glioblastoma.

PMID- 23961810
TI  - Phytophthora database 2.0: update and future direction.
AB  - The online community resource Phytophthora database (PD) was developed to support
      accurate and rapid identification of Phytophthora and to help characterize and
      catalog the diversity and evolutionary relationships within the genus. Since its
      release in 2008, the sequence database has grown to cover 1 to 12 loci for ~2,600
      isolates (representing 138 described and provisional species). Sequences of
      multiple mitochondrial loci were added to complement nuclear loci-based
      phylogenetic analyses and diagnostic tool development. Key characteristics of
      most newly described and provisional species have been summarized. Other
      additions to improve the PD functionality include: (i) geographic information
      system tools that enable users to visualize the geographic origins of chosen
      isolates on a global-scale map, (ii) a tool for comparing genetic similarity
      between isolates via microsatellite markers to support population genetic
      studies, (iii) a comprehensive review of molecular diagnostics tools and relevant
      references, (iv) sequence alignments used to develop polymerase chain reaction
      based diagnostics tools to support their utilization and new diagnostic tool
      development, and (v) an online community forum for sharing and preserving
      experience and knowledge accumulated in the global Phytophthora community. Here
      we present how these improvements can support users and discuss the PD's future
      direction.

PMID- 23961811
TI  - Surgical portosystemic shunts in the era of TIPS and liver transplantation are
      still relevant.
AB  - BACKGROUND: The surgical portosystemic shunts (PSS) are a time-proven modality
      for treating portal hypertension. Recently, in the era of liver transplantation
      and the transjugular intrahepatic portosystemic shunts (TIPS), use of the PSS has
      declined. OBJECTIVES: This study was conducted to evaluate changes in practice,
      referral patterns, and short- and longterm outcomes of the use of the surgical
      PSS before and after the introduction of the Model for End-stage Liver Disease
      (MELD). METHODS: A retrospective analysis of 47 patients undergoing PSS between
      1996 and 2011 in a single university hospital was conducted. RESULTS: Subgroups
      of patients with cirrhosis (53%), Budd-Chiari syndrome (13%), portal vein
      thrombosis (PVT) (26%), and other pathologies (9%) differed significantly with
      respect to shunt type, Child-Pugh class, MELD score and perioperative mortality.
      Perioperative mortality at 60 days was 15%. Five-year survival was 68% (median:
      70 months); 5-year shunt patency was 97%. Survival was best in patients with PVT
      and worst in those with Budd-Chiari syndrome compared to other subgroups. Patency
      was better in the subgroups of patients with cirrhosis and other pathologies
      compared with the PVT subgroup. Substantial changes in referral patterns
      coincided with the adoption of the MELD in 2002, with decreases in the incidence
      of cirrhosis and variceal bleeding, and increases in non-cirrhotics and
      hypercoagulopathy. CONCLUSIONS: Although the spectrum of diseases benefiting from
      surgical PSS has changed, surgical shunts continue to constitute an important
      addition to the surgical armamentarium. Selected subgroups with variceal bleeding
      in well-compensated cirrhosis and PVT benefit from the excellent longterm patency
      offered by the surgical PSS.

PMID- 23961812
TI  - [Warfarin - its synthesis and properties in a twenty-year retrospective*].
AB  - The review paper deals with some aspects of warfarin history and its use, at the
      beginning as a rodenticide and later as an anticoagulant. It describes its
      principal physical-chemical properties and it analyzes schematically the
      possibilities of its preparation by both selective and non-selective synthesis
      from coumarin derivatives. A survey of syntheses and its results are tabulated,
      including the literary references, and the paper is concluded with an evaluation
      of the prospects of this agent in comparison with alternative anticoagulants and
      its advantages, disadvantages and prospects.

PMID- 23961813
TI  - Influence of formulation and process parameters on the characteristics of PLGA
      based microparticles with controlled drug release.
AB  - PLGA microparticles for sustained release of ibuprofen as the model drug were
      prepared by the O/W solvent evaporation method under altering stirring speed
      (600, 1000 rpm), emulsifier concentration (PVA concentration 0.1%, 1%) and
      organic solvent selection (dichloromethane, ethyl acetate). The obtained results
      confirmed the effect of selected formulation and process parameters on the
      properties of prepared PLGA-based microparticles. An influence on encapsulation
      efficiency, yield, morphological properties, mean size and drug release was
      observed. Increased stirring speed within the solvent evaporation process
      resulted in a decrease of encapsulation efficiency, yield and mean size but the
      incorporated drug was released faster. Increased PVA concentration in the
      external emulsion phase brought the same results except the ibuprofen release
      rate. Microparticles prepared with dichloromethane as the organic solvent
      exhibited higher sphericity, a more regular shape with a smooth surface, and thus
      dichloromethane was considered to be a more suitable organic solvent in
      comparison with ethyl acetate for this purpose.

PMID- 23961814
TI  - A study of a new co-processed dry binder based on spray-dried lactose and
      microcrystalline cellulose.
AB  - The paper studies the compressibility and disintegration time of tablets from the
      co-processed dry binder DisintequikTM MCC in combination with two lubricants at
      two concentrations in dependence on compression force. It also compares identical
      parameters in the physical mixtures of the spray-dried lactose Flowlac(r) 100 and
      the microcrystalline cellulose Microcel(r) MC-102 in the ratios of 9 : 1, 8 : 2
      and 7 : 3, again in combination with two lubricants of two concentrations at one
      compression force. The lubricants employed are magnesium stearate and poloxamer
      407 in concentrations of 1% and 2%. Compressibility is evaluated by means of
      energy balance of compression and tensile strength of tablets. DisintequikTM MCC
      shows higher values of total energy of compression due to higher values of the
      energy accumulated by the tablet, higher plasticity, higher strength and a longer
      disintegration time of tablets than the physical mixture of spray-dried lactose
      and microcrystalline cellulose of a corresponding content. .

PMID- 23961815
TI  - Study of local anaesthetics: part 201. Determination of the critical micellar
      concentration of pentacaine hydrochloride from the measurements of UV absorption
      of pyrene in methanol solutions.
AB  - The formation of micelles of the local anaesthetic pentacaine hydrochloride (K
      1902) in methanol solutions at two concentrations was investigated by measuring
      the absorbance of pyrene in surfactant solution. The absorbance vs. surfactant
      concentration profiles for all the major UV spectral peaks of pyrene have been
      found to be sigmoidal in nature which were analyzed according to Sigmoidal
      Boltzmann equation to evaluate the cmcs values of the studied systems. The
      influence of the methanol concentration on the critical micellar concentration
      was studied. The observed critical micellar concentration rises with an
      increasing of alcohol.

PMID- 23961816
TI  - HPLC determination of saccharides after pre-column derivatization in honey
      samples.
AB  - The work is focused on the quality evaluation of Slovak honey samples on the
      basis of minor saccharide contents. The samples included unifloral and
      multifloral types of honeys. The saccharide contents were determined by HPLC with
      fluorescence detection. Derivatization of sugars with dansylhydrazine was used to
      increase detection sensitivity. The C18 type stationary phase was used for the
      separation of analytes and the mixture of acetonitrile and acetic acid was used
      as the mobile phase. The determined carbohydrates were saccharose, maltose,
      turanose, and also the main sugars glucose and fructose. Limits of detection were
      in the range from 15 to 100 MUg.ml-1 and suggest that low quantities of all
      studied compounds can be detected. Differences in saccharide contents between
      Slovak samples and samples from different geographical regions (France, Croatia)
      for maltose, turanose and also for saccharose were obtained. Using multivariate
      statistical treatment, Slovak honeys can be distinguished from other tested
      honeys using the saccharide profiles.

PMID- 23961817
TI  - [Use of human medicinal preparations in veterinary medicine].
AB  - The paper aims to analyze the development of the consumption of human and
      veterinary medicinal preparations used in veterinary practice in the Czech
      Republic and the dynamics of the individual ATC groups in the years 2001-2008. In
      human ATC groups, 14 ATC were examined. The researchers examined trading both
      from the view of the number of items and their volume. A set of 15 veterinary ATC
      groups was analogically analyzed. In the set of human ATC groups, in most cases a
      gradual increase in the number of sold packages and items was observed, in the
      case of veterinary ATC groups this trend was not observed excepting the ATC
      groups QC03 - cardiovascular system, QP09 - antiparasitics and QV20 - various.
      One of the elements under study was the determination of the number of active
      ingredients in the selected ATC group A - the digestive tract and metabolism. In
      this largest ATC group of the comparative sets, the numbers of active ingredients
      in the given time axis as well as the number of medicinal preparations containing
      these ingredients were determined. The set included only the preparations with
      one active ingredient and when looking at their development in the course of time
      it can be stated that of the original 51 preparations 145 items were traded at
      the end of the monitored period and the number of active ingredients was extended
      from 31 to 59. It results from the analysis that in the course of years there
      occurs an increase in the number of human medicinal preparations employed for
      pharmacotherapy in veterinary medicine.

PMID- 23961819
TI  - Separate representation of stimulus frequency, intensity, and duration in
      auditory sensory memory: an event-related potential and dipole-model analysis.
AB  - Abstract The present study analyzed the neural correlates of acoustic stimulus
      representation in echoic sensory memory. The neural traces of auditory sensory
      memory were indirectly studied by using the mismatch negativity (MMN), an event
      related potential component elicited by a change in a repetitive sound. The MMN
      is assumed to reflect change detection in a comparison process between the
      sensory input from a deviant stimulus and the neural representation of repetitive
      stimuli in echoic memory. The scalp topographies of the MMNs elicited by pure
      tones deviating from standard tones by either frequency, intensity, or duration
      varied according to the type of stimulus deviance, indicating that the MMNs for
      different attributes originate, at least in part, from distinct neural
      populations in the auditory cortex. This result was supported by dipole-model
      analysis. If the MMN generator process occurs where the stimulus information is
      stored, these findings strongly suggest that the frequency, intensity, and
      duration of acoustic stimuli have a separate neural representation in sensory
      memory. 

PMID- 23961818
TI  - Analysis of the consumption of sedative and hypnotic drugs in Yemen and the Czech
      Republic.
AB  - The aim of this project is to analyze the consumption and reasons for the use of
      sedative and hypnotic drugs (ATC: N05B and N05C) (SHD) in Yemen (YEM) and to
      compare this with the consumption of SHD in the Czech Republic (CZ) and in YEM,
      in the years 2000-2005. In 2005 the consumption of SHD in YEM and in CZ was 0.20
      and 6.9 USD/1000 citizens/day, respectively. The consumption of SHD in YEM and in
      CZ increased after 2000 by 637% and 85%, respectively. A pilot questionnaire
      tested the factors influencing the consumption of SHD in YEM. 72% of respondents
      were male; 48% had obtained SHD the first time without a prescription; 90% had
      engaged in the long term use of SHD; 43% did not know the risks of SHD and the
      majority of users are most likely young people. The increasing consumption of SHD
      may be caused by the frequent prescribing of drugs for off-label use, obtaining
      SHD in the pharmacy without prescription and the common chewing of qat and the
      lack of warnings about long term risks.

PMID- 23961820
TI  - Susceptibility to Memory Interference Effects following Frontal Lobe Damage:
      Findings from Tests of Paired-Associate Learning.
AB  - Abstract Patients with frontal lobe lesions were adminstered tests of paired
      associate learning in which cue and response words are manipulated to increase
      interference across two study lists. In one test of paired-associate learning (AB
      AC test), cue words used in one list are repeated in a second list but are
      associated with different response words (e.g., LION-HUNTER, LION-CIRCUS). In
      another test (AB-ABr test), words used in one list are repeated in a second list
      but are rearranged to form new pairs. Compared to control subjects, patients with
      frontal lobe lesions exhibited disproportionate impairment of second-list
      learning as a result of interference effects. In particular, patients exhibited
      the poorest performance during the initial trial of the second list, a trial in
      which interference effects from the first list would be most apparent. These
      findings suggest that the on-line control of irrelevant or competing memory
      associations is disrupted following frontal lobe lesions. This disruption may be
      indicative of an impaired gating or filtering mechanism that affects not only
      memory function but other cognitive function as well. 

PMID- 23961821
TI  - ERP Measures Assay the Degree of Expectancy Violation of Harmonic Contexts in
      Music.
AB  - Abstract Expectancy violations of a highly constrained musical context were
      studied by presenting subjects with a chord sequence (I, IV, V) that generated a
      strong expectancy for a specific final chord, and then completing the sequence
      with either a "best-possible" (Tonic), harmonically plausible (Minor), or
      harmonically implausible (Dissonant) resolution. Subjects determined whether it
      was the best-possible resolution, and in one-half of the trials made their
      decision known with an overt response. Several ERP waveform components showed
      differences among resolution types, response conditions, and electrode locations.
      Among the affected components were two subclasses of the P300, the first of which
      (P3a) was largest in response to the Dissonant in both response conditions at all
      electrode sites. The area and peak amplitude of the P3b varied at several
      electrode sites as a function of the degree of expectancy violation represented
      by the resolutions. The peak latency of the P3b component reflected the
      behavioral response time measurement in which the Tonic and Dissonant were
      identified 300 msec more quickly than the Minor. A comparison between frequency
      and timedomain data analyses demonstrates several parallels, and it is concluded
      that both can serve to investigate the perception and processing of the
      probability structure underlying musical events and contexts. 

PMID- 23961822
TI  - Agrammatism: behavioral description and neurobiological explanation.
AB  - Abstract Subjects with brain damage resulting in agrammatic aphasia frequently
      omit or substitute function items (function words and inflectional affixes).
      However, they show only mild deficits in using meaningful content words.
      Agrammatics' performance on comprehension tests reveals a rather complex pattern.
      They usually understand active sentences correctly, but perform on chance level
      on passives. The same contrast is observed for more complex sentence types, such
      as subject vs. object clefts or relatives. This complex comprehension pattern
      suggests that agrammatism is a syntactic disturbance that selectively affects
      particular sentence structures. Nevertheless, it is possible that both the
      production and comprehension patterns go back to an access problem for
      grammatical morphemes. If an agrammatic aphasic comprehends only 50% of these
      morphemes, she or he may well be problem-free in understanding the resulting
      "pruned" active sentences in which some of the grammatical morphemes are missing.
      In contrast, she or he is likely to arrive at the wrong meaning when confronted
      with "pruned" passives. This hypothesis raises the question of how fully
      competent speakers interpret ungrammatical "pruned" strings derived from well
      formed sentences by systematically deleting function items. Experimental data
      demonstrate that competent speakers approximate the agrammatic comprehension
      pattern when being presented with "pruned" strings. This argues that agrammatism
      can, indeed, be viewed as a deficit in processing function words and inflectional
      affixes, which may manifest itself in production and/or comprehension tasks.
      Assuming that cortical cell assemblies with distinct topographies correspond to
      content words and grammatical morphemes, it is possible to explain agrammatism in
      terms of lesions to these neuronal networks. This neurobiological model can
      explain additional aspects of agrammatics' performance. 

PMID- 23961823
TI  - Frames of reference for hand orientation.
AB  - Abstract In reaching and grasping movements, information about object location
      and object orientation is used to specify the appropriate proximal arm posture
      and the appropriate positions for the wrist and fingers. Since object orientation
      is ideally defined in a frame of reference fixed in space, this study tested
      whether the neural control of hand orientation is also best described as being in
      this spatial reference frame. With the proximal arm in various postures, human
      subjects used a handheld rod to approximate verbally defined spatial
      orientations. Subjects did quite well at indicating spatial vertical and spatial
      horizontal but made consistent errors in estimating 45 degrees  spatial slants.
      The errors were related to the proximal arm posture in a way that indicated that
      oblique hand orientations may be specified as a compromise between a reference
      frame fixed in space and a reference frame fixed to the arm. In another
      experiment, where subjects were explicitly requested to use a reference frame
      fixed to the arm, the performance was consistently biased toward a spatial
      reference frame. The results suggest that reaching and grasping movements may be
      implemented as an amalgam of two frames of reference, both neurally and
      behaviorally. 

PMID- 23961824
TI  - Is there a social module? Language, face processing, and theory of mind in
      individuals with williams syndrome.
AB  - Abstract Many species can respond to the behavior of their conspecifics. Human
      children, and perhaps some nonhuman primates, also have the capacity to respond
      to the mental states of their conspecifics, i.e., they have a "theory of mind."
      On the basis of previous research on the theory-of-mind impairment in people with
      autism, together with animal models of intentionality, Brothers and Ring (1992)
      postulated a broad cognitive module whose function is to build representations of
      other individuals. We evaluate the details of this hypothesis through a series of
      experiments on language, face processing, and theory of mind carried out with
      subjects with Williams syndrome, a rare genetic neurodevelopmental disorder
      resulting in an uneven lin-guisticocognitive profile. The results are discussed
      in terms of how the comparison of different phenotypes (e.g., Williams syndrome,
      Down syndrome, autism, and hydrocephaly with associated myelomeningocele) can
      contribute both to understanding the neuropsychology of social cognition and to
      current thinking about the purported modularity of the brain. 

PMID- 23961825
TI  - Word and nonword repetition within- and across-modality: an event-related
      potential study.
AB  - Abstract The effects on event-related potentials (ERPs) of within- and across
      modality repetition of words and nonwords were investigated. In Experiment 1,
      subjects detected occasional animal names embedded in a series of words. AU items
      were equally likely to be presented auditorily or visually. Some words were
      repetitions, either within- or across-modality, of words presented six items
      previously. Visual-visual repetition evoked a sustained positive shift, which
      onset around 250 msec and comprised two topographically and temporally distinct
      components. Auditory-visual repetition modulated only the later of these two
      components. For auditory EMS, within- and across-modality repetition evoked
      effects with similar onset latencies. The within-modality effect was initially
      the larger, but only at posterior sites. In Experiment 2, critical items were
      auditory and visual nonwords, and target items were auditory words and visual
      pseudohomophones. Visual-visual nonword repetition effects onset around 450 msec,
      and demonstrated a more anterior scalp distribution than those evoked by auditory
      visual repetition. Visual-auditory repetition evoked only a small, late-onsetting
      effect, whereas auditory-auditory repetition evoked an effect that, at parietal
      sites only, was almost equivalent to that from the analogous condition of
      Experiment 1. These findings indicate that, as indexed by ERF's, repetition
      effects both within- and across-modality are influenced by lexical status.
      Possible parallels with the effects of word and nonword repetition on behavioral
      variables are discussed. 

PMID- 23961826
TI  - Inducing Agrammatic Profiles in Normals: Evidence for the Selective Vulnerability
      of Morphology under Cognitive Resource Limitation.
AB  - Abstract The selective vulnerability of morphology in agrammatic aphasia is often
      interpreted as evidence that closedclass items reside in a particular part of the
      brain (i.e., Broca's area); thus, damage to a part of the language processor maps
      onto behavior in a transparent fashion. We propose that the selective
      vulnerability of grammatical morphemes in receptive processing may be the result
      of decrements in overall processing capacity, and not the result of a selective
      lesion. We demonstrate agrammatic profiles in healthy adults who have their
      processing capacity diminished by engaging in a secondary task during testing.
      Our results suggest that this selective profile does not necessarily indicate the
      existence of a distinct subsystem specialized for the implicated aspects of
      syntax, but rather may be due to the vulnerability of these forms in the face of
      global resource diminution, at least in grammaticality judgment. 

PMID- 23961827
TI  - Recognition of CVC Syllables from LVF, RVF, and Central Locations: Hemispheric
      Differences and Interhemispheric Interaction.
AB  - Abstract In each of two experiments, subjects were required to identify consonant
      vowel-consonant nonsense syllables projected to the left visual fiel/right
      hemisphere (LVF/RH), right visual field/left hemisphere (RVF/LH), or to the
      CENTER of the visual field. There were fewer errors on RVF/LH than on LVF/RH
      trials and the pattern of errors was qualitatively different on RVF/LH and LVF/RH
      trials. The pattern of errors was consistent with the hypothesis that attention
      is distributed across the three letters in a relatively slow serial fashion on
      LVF/RH trials whereas attention is distributed more rapidly and evenly across the
      three letters on RVF/LH trials. Despite the large RVF/LH advantage, the
      qualitative pattern of errors on CENTER trials (when viewing conditions do not
      favor one hemisphere or the other) was very similar to the pattern obtained on
      LW/RH trials. Implications of this counterintuitive finding are considered for
      the nature of interhemispheric interaction. 

PMID- 23961828
TI  - Intermediate-level visual representations and the construction of surface
      perception.
AB  - Abstract Visual processing has often been divided into three stages-early,
      intermediate, and high level vision, which roughly correspond to the sensation,
      perception, and cognition of the visual world. In this paper, we present a
      network-based model of intermediate-level vision that focuses on how surfaces
      might be represented in visual cortex. We propose a mechanism for representing
      surfaces through the establishment of "ownership"-a selective binding of contours
      and regions. The representation of ownership provides a central locus for visual
      integration. Our simulations show the ability to segment real and illusory images
      in a manner consistent with human perception. In addition, through ownership,
      other processes such as depth, transparency, and surface completion can interact
      with one another to organize an image into a perceptual scene. 

PMID- 23961829
TI  - Surface area of human cerebral cortex and its gross morphological subdivisions:
      in vivo measurements in monozygotic twins suggest differential hemisphere effects
      of genetic factors.
AB  - Abstract We measured the surEdce area of the cerebral cortex and its gross
      morphological subdivisions in 10 pairs of monozygotic twins. Cortical surface
      area was estimated in vivo using magnetic resonance imaging and threedimensional
      computer models of the intra- and extrasulcal pial surface. The means and
      standard deviations of regional (e.g., gyral), lobar, hemisphere, and total
      cortical surface area were tabulated for the entire population of 20 young, right
      handed adults (10 females, 10 males). To determine whether genotypic differences
      were associated with morphometric differences, analyses of variance were carried
      out on each measure across unrelated twin pairs (genotype factor) and within co
      twins (birth order factor). Across unrelated pairs, there was wide variation in
      regional cortical surface area for the left hemisphere (normalized by total
      cortical surface area, p <= 0.0001) but not for the right hemisphere (normalized,
      p = 0.12). More variation in lobar surface area was also observed for the left
      hemisphere (normalized, p = 0.05) than for the right (normalized, p = 0.48).
      Within co-twins, no signifcant variation in regional surface area or lobar
      surface area was found for the left or right hemisphere. Although normalized
      regional and lobar surface area in the left hemisphere differed across unrelated
      pairs, overall left hemisphere surface area normalized by total cortical surface
      area did not (p = 0.73). Total cortical surface area normallzed by body weight
      varied across unrelated pairs (p = 0.001) but not within co-twins (p = 0.39). The
      effects observed across unrelated pairs were not attributable to sex differences.
      These results suggest: 1) both the total area and folding of the cortical surface
      are heavily influenced by genetic factors in humans; and 2) the cerebral
      hemispheres may be differentially affected by genetic influences on cortical
      morphogenesis, with the languagedominant left cerebral cortex under stronger
      genetic control than the right. 

PMID- 23961830
TI  - Interview with alfonso caramazza.
AB  - Abstract Alfonso Caramazza is the David T. McLaughlin Distinguished Professor at
      Dartmouth College. He received the B.A. degree in psychology from McGill
      University in 1970 and the Ph.D. from Johns Hopkins University in 1974. He joined
      the Hopkins faculty in 1974 and taught there first in the Psychology Department
      and then in the Cognitive Science Department, which he helped create. In 1993 he
      joined the faculty at Dartmouth College. Although his research has focused
      primarily on the neuropsychology of language processes, he has also made
      contributions in the areas of normal psycholinguistics, naive physics, and, more
      recently, perception and attention. Caramazza has been the recipient of a Javits
      Neuroscience Award and an honorary doctorate from the Catholic University of
      buvain. 

PMID- 23961831
TI  - Investigation of the rat model for preclinical evaluation of pH-dependent oral
      absorption in humans.
AB  - Many pharmaceutically active compounds are weak electrolytes and are ionizable in
      the pH range experienced throughout the gastrointestinal tract. Changes in
      protonation state due to pH changes in the gut can have dramatic effects on
      solubility, dissolution, and permeation through biological barriers. Preclinical
      assessment of the pH-dependence of oral absorption is critical for compounds
      possessing pH-dependent solubility. Here we examine pH-dependent solubility and
      oral exposure in rat for three model compounds, dasatinib, ketoconazole, and
      mefenamic acid. Dasatinib and ketoconazole are both weak bases, while mefenamic
      acid is a carboxylic acid. The effects of gastric pH modulators, pentagastrin and
      famotidine, were investigated in rat PK studies to assess the applicability of
      using the rat to evaluate the risk of pH-dependent oral exposure for ionizable
      compounds. Dasatinib showed similar exposure between control and pentagastrin
      pretreated groups, and 4.5-fold lower AUC in famotidine-pretreated rats.
      Ketoconazole showed a 2-fold increase in AUC in pentagastrin-treated rats
      relative to control, and 4.5-fold lower AUC in famotidine treated rats, relative
      to the pentagastrin group. Mefenamic acid showed highly similar exposures among
      control, pentagastrin-pretreated, and famotidine-pretreated groups. The rat model
      was shown to be useful for compounds displaying pH-dependent solubility and oral
      absorption that may be affected by gastric pH modulators. 

PMID- 23961832
TI  - Electrocatalytic O2 reduction reaction by synthetic analogues of cytochrome P450
      and myoglobin: in-situ resonance Raman and dynamic electrochemistry
      investigations.
AB  - Bioinspired electrodes have been constructed by physiabsorption of two air stable
      iron porphyrin complexes, one bearing an imidazole coordination and the other
      bearing a thiolate coordination. To control the electron transfer (ET) rate to
      these O2 reducing electrocatalysts, the complexes were immobilized on edge plane
      graphite electrode and alkyl thiol self-assembled monolayer (SAM) modified Au
      electrodes with varying chain lengths of the thiols. Catalyst immobilized SAM
      modified surfaces were characterized using surface enhanced resonance Raman
      spectroscopy (SERRS), and their electrocatalytic O2 reduction properties were
      investigated using rotating ring disc electrochemistry (RRDE). While the
      imidazole bound complex showed increase in partially reduced oxygen species
      (PROS) on decreasing ET rate, the thiolate bound complex showed the opposite
      trend, that is, the value of PROS reduced on decreasing the ET rate. SERRS
      coupled to rotating disc electrochemistry (SERRS-RDE) technique helps gain
      insight into the O2 reduction mechanism. The results obtained indicate that while
      the imidazole bound iron porphyrin complex reduces O2 through an inner sphere
      mechanism using a high-spin (HS) Fe(II) species, the thiolate ligated complex
      shows an inner sphere as well as outer sphere mechanism using a HS Fe(II) and low
      spin (LS) Fe(II) species, respectively. The PROS formation by a HS Fe(II) species
      of this thiolate bound complex increases with decreasing ET rates while that of a
      LS Fe(II) species decreases with decreasing ET rates. 

PMID- 23961833
TI  - Cost-effectiveness analysis of Recovery Management Checkups (RMC) for adults with
      chronic substance use disorders: evidence from a 4-year randomized trial.
AB  - AIMS: This study performs the first cost-effectiveness analysis (CEA) of Recovery
      Management Checkups (RMC) for adults with chronic substance use disorders.
      DESIGN: Cost-effectiveness analysis of a randomized clinical trial of RMC.
      Participants were assigned randomly to a control condition of outcome monitoring
      (OM-only) or the experimental condition OM-plus-RMC, with quarterly follow-up for
      4 years. SETTING: Participants were recruited from the largest central intake
      unit for substance abuse treatment in Chicago, Illinois, USA. PARTICIPANTS: A
      total of 446 participants who were 38 years old on average, 54% male, and
      predominantly African American (85%). MEASUREMENTS: Data on the quarterly cost
      per participant come from a previous study of OM and RMC intervention costs.
      Effectiveness is measured as the number of days of abstinence and number of
      substance use-related problems. FINDINGS: Over the 4-year trial, OM-plus-RMC cost
      on average $2184 more than OM-only (P < 0.01). Participants in OM-plus-RMC
      averaged 1026 days abstinent and had 89 substance use-related problems. OM-only
      averaged 932 days abstinent and reported 126 substance use-related problems. Mean
      differences for both effectiveness measures were statistically significant (P <
      0.01). The incremental cost-effectiveness ratio for OM-plus-RMC was $23.38 per
      day abstinent and $59.51 per reduced substance-related problem. When additional
      costs to society were factored into the analysis, OM-plus-RMC was less costly and
      more effective than OM-only. CONCLUSIONS: Recovery Management Checkups are a cost
      effective and potentially cost-saving strategy for promoting abstinence and
      reducing substance use-related problems among chronic substance users.

PMID- 23961834
TI  - The potential for measuring ethnicity and health in a multicultural milieu--the
      case of type 2 diabetes in Australia.
AB  - OBJECTIVE: Ethnicity influences health in many ways. For example, type 2 diabetes
      (T2DM) is disproportionately prevalent among certain ethnic groups. Assessing
      ethnicity is difficult, and numerous proxy measures are used to capture its
      various components. Australian guidelines specify a set of variables for
      measuring ethnicity, and how such parameters should be categorised. Using T2DM
      data collections as an illustrative example, this study sought to examine how
      ethnicity is measured in Australian health databases and, by comparing current
      practice with Australia's existing benchmark recommendations, to identify
      potential areas for improvement of the health data landscape. DESIGN: We
      identified databases containing information from which ethnic group-specific
      estimates of T2DM burden may be gleaned. For each database, details regarding
      ethnicity variables were extracted, and compared with the Australian guidelines.
      RESULTS: Data collection instruments for 32 relevant databases were reviewed.
      Birthplace was recorded in 27 databases (84%), but mode of birthplace assessment
      varied. Indigenous status was commonly recorded (78%, n=25), but only nine
      databases recorded other aspects of self-perceived race/ethnicity. Of 28
      survey/audit databases, 14 accommodated linguistic preferences other than
      English, and 11 either excluded non-English speakers or those for whom a
      translator was not available, or only offered questionnaires in English.
      CONCLUSIONS: Considerable variation exists in the measurement of ethnicity in
      Australian health data-sets. While various markers of ethnicity provide
      complementary information about the ethnic profile within a data-set, non-uniform
      measurement renders comparison between data-sets difficult. A standardised
      approach is necessary, and identifying the ethnicity variables that are
      particularly relevant to the health sector is warranted. Including self
      identified ethnicity in Australia's set of recommended indicators and as a core
      component of the national census should be considered. Globalisation and
      increasing migration mean that these findings have implications internationally,
      including for multi-ethnic countries throughout North America and Europe.

PMID- 23961835
TI  - Australian general practitioner perceptions of the detection and screening of at
      risk drinking, and the role of the AUDIT-C: a qualitative study.
AB  - BACKGROUND: At-risk drinking is common in Australia. Validated screening tools
      such as the AUDIT-C have been promoted to general practitioners (GPs), but appear
      rarely used and detection of at-risk drinking in primary care remains low. We
      sought to describe Australian GP perceptions of the detection and screening of at
      risk drinking; to understand their low uptake of alcohol screening
      questionnaires, and in particular, their attitude to the adoption of the AUDIT-C.
      METHODS: Semi-structured focus group interviews of four groups of GPs and GP
      trainees were conducted in metropolitan Sydney between August and October 2011.
      Audio recordings were transcribed and analysed using grounded theory methodology.
      RESULTS: We identified four main themes: there was consensus that detecting at
      risk drinking is important but difficult to do, social and cultural attitudes to
      alcohol consumption affect willingness to ask questions about its use, the
      dynamics of patient-doctor interactions are important, and alcohol screening
      questionnaires lack practical utility. Analysis suggests that the conceptual
      barriers to detecting at-risk drinking were: community stigma and stereotypes of
      "problem drinking", GP perceptions of unreliable patient alcohol use histories,
      and the perceived threat to the patient-doctor relationship. CONCLUSION: This
      small exploratory study found that the practice of, and barriers to, detecting at
      risk drinking appear to be inextricably linked to the sociocultural beliefs
      surrounding alcohol use. Screening questionnaires such as the AUDIT-C are not
      designed to address these issues. In the current context, it is unlikely that
      approaches that focus on the use of these tools will be effective at improving
      detection of at-risk drinking by GPs.

PMID- 23961836
TI  - An operational analysis of a one-handed catching task using high speed
      photography.
AB  - A standardized one-handed catching task was set up in the laboratory and
      performances of four competent Ss were recorded using a high speed photographic
      technique. Motor performance could be described in two sequential parts:
      orientation of the catching hand followed by a ballistic grasping movement.
      Successful performance of the task appeared to depend upon accurate organization
      of both these components, but emphasis lay upon spatial and temporal elements,
      respectively. The control of both phases involved prediction of the ball's motion
      from flight information sampled relatively early in the trajectory. 

PMID- 23961837
TI  - Effects of number of alternatives on the psychological refractoriness of an
      extended movement .
AB  - The single-channel prediction that delays in RT2 should be proportional to RT1
      was examined by varying the number of alternatives (one, two, or three) in the
      primary response which was an extended arm swing at maximal speed. The second
      response was a thumb key release. Foreperiods were 2, 3, or 4 sec., and
      interstimulus intervals (ISIs) ranged from .10:50 sec. in .10-sec. steps. General
      support for the single-channel model was found in that RT2 paralleled changes in
      RT1. However, RT2 was greater than predicted when the second signal (S2) occurred
      during the execution of the primary response. In addition, while delays in RT2 as
      a function of ISI - RT1 showed corresponding differences between choice
      conditions, most values were greater than predicted. The deviations from the
      single-channel model appeared to be explained best in terms of a decrease in
      readiness to respond to the second signal as ISI lengthened. 

PMID- 23961838
TI  - Recall and recognition in motor learning.
AB  - An attempt was made to manipulate motor recognition but not recall as a test of
      Adams' (1971) two-process closed-loop theory of motor learning: Ss (N = 60) wre
      given 70 KR acquisition trials of a rapid linear timing task prior to performing
      40 KR withdrawal trials under a 2(vision) * 2(audition) design where the feedback
      variables each had two levels of feedback present or absent. Feedback withdrawal
      produced a decrement in response recognition but not recall during the initial
      phase of KR withdrawal. Thereafter the recognition and recall processes tended to
      operate in unison. The discussion focused on the relationship between these
      processes which, as the present data suggest, may reflect fundamentally different
      underlying mechanisms. 

PMID- 23961839
TI  - The development of perceptual motor sequencing ability.
AB  - The purposes of this study were (a) to investigate the possibility that short
      term memory may be a limiting factor in the development of perceptual-motor
      sequencing ability, (b) to determine whether sex differences exist in sequencing
      ability, (c) to determine whether organized information facilitates serial
      recall, and (d) to ascertain whether the recall of serial perceptual-motor
      responses results in a bow-shaped serial-position curve. A 2 * 2 * 3 factorial
      design was used to analyze the independent variables of age, sex, and pattern
      organization. Further, an age * serial position ANOVA was performed to
      investigate the serial-position curve. Serial recall improved with age; however
      young children experienced difficulty in recalling a complex task. The poor
      recall performance of 5-yr.-old children was discussed in terms of the
      possibility that young children fail to use labeling strategies to facilitate
      recall. No sex differences were found. A primacy effect was obtained on the
      complex task. 

PMID- 23961840
TI  - Response programming in simple and choice reactions.
AB  - Changing the nature of a motor response can produce a reliable change in choice
      reaction time, while the corresponding effect for simple reaction time is
      unreliable, and disappears with appropriate instructions and practice. The
      reliable effect for choice reactions was attributed to a component of the
      reaction time in which the response is programmed. This programming can be done
      in advance of the simple reaction-time interval thereby eliminating this
      component from the measured simple reaction time, although S may not necessarily
      take advantage of this possibility. According to this analysis, the Henry and
      Rogers "memory drum theory(") applies to choice reactions but not necessarily to
      the simple reactions which have been the primary basis for previous
      demonstrations. 

PMID- 23961841
TI  - Differential errors of kinesthesis produced by previous limb positions.
AB  - Reports of kinesthetic after-effects indicate that the position sense of the limb
      is labile. It was hypothesized that varying the starting positions of a limb
      would be an important factor in determining the post-treatment accuracy of
      kinesthesia. An experiment is described in which the right arm was horizontally
      abducted to one of two treatment positions. The effect of exposure time at each
      of these positions was assessed for a set of testing positions by measuring
      subsequent accuracy of visual localization of the unseen finger tip. There was a
      marked unidirectional shift in registered position of the treated limb, which was
      to the left following postures on the right. The magnitude of this change in
      kinesthesis was significantly greater when the treatment position was farthest
      from the test position. Exposure time affected only the nearer treatment
      position. 

PMID- 23961842
TI  - The effect of interpolated motor activity on the short-term retention of movement
      distance and end-location.
AB  - The effect of an interpolated movement on the recall of a blind, lever
      positioning movement was assessed separately for the reproduction cues of
      distance and end-location. Both cues showed the context effect of assimilation,
      that is, the end-location of the interpolated movement caused directional biasing
      of the algebraic or constant error (CE) for location reproduction while the
      length of the interpolated movement caused similar directional biasing for
      distance reproduction. Variability about algebraic error (VE) was used to assess
      forgetting. There was no change in VE for location reproduction, and an increase
      in VE for distance reproduction was limited to the relatively large movements.
      Thus, an interpolated movement that does not have to be remembered does not cause
      interference with the retention of location information, but does cause some
      interference with the retention of distance information. The findings are
      discussed in relation to a model of motor short-term memory which incorporates
      both CE and VE. 

PMID- 23961843
TI  - An alternative test of the adams-creamer decay hypothesis in timing motor
      responses.
AB  - Ss were randomly assigned to either a vestibular proprioception (VP) group (N =
      30) or a no vestibular proprioception (NVP) group (N = 30). The VP group was
      tested while supine on a table rotated 60 deg. in the vertical plane and, at the
      cessation of rotation, Ss estimated a 2-sec. interval. Procedures were identical
      for the NVP group with the exception that they received no body rotation. All Ss
      received 40 trials and knowledge of results was given during a 20-sec. intertrial
      interval. The VP group had significantly smaller mean absolute and algebraic
      error scores than the NVP group. The difference between the mean variable error
      scores of the two groups was not significant. Results supported the Adams-Creamer
      decay hypothesis in terms of absolute error scores and algebraic error scores,
      but did not support the hypothesis in terms of variable error scores. 

PMID- 23961844
TI  - Absolute error.
AB  - The position that a composite error score is not an interpretable indicator of
      motor performance is supported and expanded. It is shown that Henry's E(2)
      statistic possesses the same deficiencies as A (2), and thus is equally invalid.
      Responses are made to a number of specific criticisms of the Schutz and Roy paper
      made by Henry. 

PMID- 23961845
TI  - A new link between stress response and nucleolar function during pollen
      development in Arabidopsis mediated by AtREN1 protein.
AB  - Heat shock transcription factors (Hsfs) are involved in multiple aspects of
      stress response and plant growth. However, their role during male gametophyte
      development is largely unknown, although the generative phase is the most
      sensitive and critical period in the plant life cycle. Based on a wide screen of
      T-DNA mutant lines, we identified the atren1 mutation (restricted to nucleolus1)
      in early male gametophytic gene At1g77570, which has the closest homology to
      HSFA5 gene, the member of a heat shock transcription factor (HSF) gene family.
      The mutation causes multiple defects in male gametophyte development in both
      structure and function. Because the mutation disrupts an early acting (AtREN1)
      gene, these pollen phenotype abnormalities appear from bicellular pollen stage to
      pollen maturation. Moreover, the consequent progamic phase is compromised as well
      as documented by pollen germination defects and limited transmission via male
      gametophyte. In addition, atren1/- plants are defective in heat stress (HS)
      response and produce notably higher proportion of aberrant pollen grains. AtREN1
      protein is targeted specifically to the nucleolus that, together with the
      increased size of the nucleolus in atren1 pollen, suggests that it is likely to
      be involved in ribosomal RNA biogenesis or other nucleolar functions. 

PMID- 23961846
TI  - The structure of pedicle and hard antler bone in the European roe deer (Capreolus
      capreolus): a light microscope and backscattered electron imaging study.
AB  - Deer antlers are deciduous bony structures that develop from permanent frontal
      outgrowths, the pedicles. While growth and bone architecture of antlers have been
      studied in greater detail, information on pedicle formation and structure is
      scarce. The present study provides information on the structure of pedicle and
      hard antler bone in the European roe deer. A pronounced seasonal variation in
      pedicle architecture was observed, with high porosity around antler casting and a
      very compact bone structure during the hard antler stage. These observations
      suggest a corresponding marked variation also in the biomechanical properties of
      the pedicles. The seasonally alternating extensive resorption and formation
      processes make the pedicles of older deer heavily remodeled structures. Pedicles
      increase in thickness by apposition of primary bone that subsequently becomes
      replaced by secondary osteons. The antler cortex of roe deer is largely composed
      of a tubular framework of woven bone trabeculae with some remnants of mineralized
      cartilage, and primary osteons that have filled in the intertrabecular spaces.
      Secondary osteons are scarce, denoting little remodeling in antlers, which can be
      related to their short lifespan. The occurrence of cement lines around primary
      osteons indicates resorption on the trabecular scaffold prior to infilling of the
      intertrabecular spaces. The outer cortex showed a higher autofluorescence and a
      more immature structure than the main cortex, suggesting that it was secondarily
      formed by periosteal activity. Pedicles and antlers constitute a functional
      entity, and future histological and/or biomechanical studies should therefore
      consider both components of the cranial appendages. 

PMID- 23961848
TI  - Goal or movement? Action representation within the primary motor cortex.
AB  - Although facilitation of the cortico-spinal system during action observation is
      widely accepted, it remains controversial whether this facilitation reflects a
      replica of the observed movements or the goal of the observed motor acts. In the
      present transcranial magnetic stimulation study, we recorded motor evoked
      potentials from two hand muscles (first dorsal interosseous and abductor digiti
      minimi) while 22 healthy participants observed a hand reaching towards and
      grasping a bottle. To test for alternative coding levels (goal vs. movement),
      three relevant aspects were systematically manipulated: the type of observed
      movement (precision grip or whole hand grasping), situational context (bottle
      positioned in front of or behind a wall-like barrier), and processing stage
      (transcranial magnetic stimulation pulse delivered at the onset of the movement
      or at the moment of contact between the fingers and the object). At movement
      onset, motor evoked potential responses reflected the program necessary to
      achieve the action goal within the situational context. During movement
      observation, however, the type of observed movement was taken into account and a
      transition towards a movement-related modulation was observed. These results
      suggest that, rather than being exclusive alternatives, goal coding and movement
      coding may relate to different processing stages. 

PMID- 23961849
TI  - Interpretive habit is strengthened by cognitive bias modification.
AB  - We investigated the nature of the memory mechanisms underlying cognitive bias
      modification by applying Jacoby's (1991) process-dissociation procedure to
      responses during the transfer task. In the two training conditions (negative and
      benign), students imagined themselves in 100 ambiguous scenarios, most with
      potentially negative resolutions; the ambiguity was resolved in a consistently
      negative or benign direction by completing the fragment of a final word. Control
      participants completed non-ambiguous, non-emotional scenarios. Next all
      participants responded on a final training block, where half of the scenarios
      were completed negatively and half benignly. Transfer was assessed by examining
      choices in the completion of test scenarios when participants were instructed to
      respond in the same way as they had to a final-block training scenario that was
      situationally similar. Benign training facilitated correct responding to benign
      analogues and impaired correct responding to negative analogues. Performance in
      the negative-training and control conditions was similar. Process-dissociation
      procedures revealed that this newly established habit and not controlled
      recollection provided the basis for transfer.

PMID- 23961847
TI  - The current status of biomarkers for predicting toxicity.
AB  - INTRODUCTION: There are significant rates of attrition in drug development. A
      number of compounds fail to progress past preclinical development due to limited
      tools that accurately monitor toxicity in preclinical studies and in the clinic.
      Research has focused on improving tools for the detection of organ-specific
      toxicity through the identification and characterization of biomarkers of
      toxicity. AREAS COVERED: This article reviews what we know about emerging
      biomarkers in toxicology, with a focus on the 2012 Northeast Society of
      Toxicology meeting titled 'Translational Biomarkers in Toxicology.' The areas
      covered in this meeting are summarized and include biomarkers of testicular
      injury and dysfunction, emerging biomarkers of kidney injury and translation of
      emerging biomarkers from preclinical species to human populations. The authors
      also provide a discussion about the biomarker qualification process and possible
      improvements to this process. EXPERT OPINION: There is currently a gap between
      the scientific work in the development and qualification of novel biomarkers for
      nonclinical drug safety assessment and how these biomarkers are actually used in
      drug safety assessment. A clear and efficient path to regulatory acceptance is
      needed so that breakthroughs in the biomarker toolkit for nonclinical drug safety
      assessment can be utilized to aid in the drug development process.

PMID- 23961851
TI  - Bullous mycosis fungoides: report of a case complicated by Kaposi's varicelliform
      eruption.
AB  - Vesiculobullous eruptions in mycosis fungoides (MF) are extremely rare. Here, we
      report a case of a 62-year-old woman presenting with erythematous patches and
      plaques of 2 years in duration, who had recently developed vesicles on
      erythematous MF plaques. Histopathological examination showed intra-subepidermal
      blisters, and infiltration of the epidermis by atypical lymphoid cells, forming
      Pautrier's microabscesses. Negative immunofluorescence excluded autoimmune
      blistering diseases. Immunohistochemistry revealed a CD4+ T-cell phenotype and
      gene rearrangement study confirmed a clonal T-cell proliferation. Kaposi's
      varicelliform eruption (KVE) developed in the patient 1 week after initiation of
      systemic corticosteroids and immunotherapy. Cluster of vesicles and erosions
      arising on the pre-existing plaque and a positive immunofluorescence test for
      Herpes simplex virus and histopathological examination confirmed the diagnosis of
      cutaneous herpes infection. This is the first case report on bullous MF
      complicated by KVE in the published work.

PMID- 23961850
TI  - Effectiveness and tolerability of second-line therapy with vildagliptin vs. other
      oral agents in type 2 diabetes: a real-life worldwide observational study (EDGE).
AB  - AIM: Real-life studies are needed to confirm the clinical relevance of findings
      from randomised controlled trials (RCTs). This study aimed to assess the
      effectiveness and tolerability of vildagliptin add-on vs. other oral
      antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting,
      and to explore the advantages and limitations of large-scale 'pragmatic' trials.
      METHODS: EDGE was a prospective, 1-year, worldwide, real-life observational study
      in which 2957 physicians reported on the effects of second-line OADs in 45,868
      patients with T2DM not reaching glycaemic targets with monotherapy. Physicians
      could add any OAD, and patients entered either vildagliptin or (pooled)
      comparator cohort. The primary effectiveness and tolerability end-point (PEP)
      evaluated proportions of patients decreasing HbA(1c) > 0.3%, without
      hypoglycaemia, weight gain, peripheral oedema or gastrointestinal side effects.
      The most clinically relevant secondary end-point (SEP 3) was attainment of end
      point HbA(1c) < 7% without hypoglycaemia or >= 3% increase in body weight.
      RESULTS: In this large group of T2DM patients, a second OAD was added at mean
      HbA(1c) of 8.2 +/- 1.3%, with no baseline HbA(1c) difference between cohorts.
      Second-line OAD therapy attained the PEP in the majority of patients, with higher
      attainment in those prescribed a vildagliptin-based regimen. The adjusted odds
      ratio was 1.49 (95% CI: 1.42, 1.55; p < 0.001). In patients with baseline HbA(1c)
      >= 7%, SEP 3 was achieved by 35% of patients on a vildagliptin-based combination
      and by 23% of those receiving comparator combinations. The adjusted odds ratio
      was 1.96 (95% CI: 1.85, 2.07; p < 0.001). Safety events were reported
      infrequently and safety profiles of vildagliptin and other OADs were consistent
      with previous data. CONCLUSION: EDGE demonstrates that in a 'real-life' setting,
      vildagliptin as second OAD can lower HbA(1c) to target without well-recognised
      OAD side effects, more frequently than comparator OADs. In addition, EDGE
      illustrates that conducting large-scale, prospective, real-life studies poses
      challenges but yields valuable clinical information complementary to RCTs.

PMID- 23961852
TI  - [What was the ASCO 2013].

PMID- 23961853
TI  - [Modern imaging techniques for anthracycline cytostatics -  review of the
      literature].
AB  - Anthracycline cytostatics can be observed at the level of organelles, cells and
      whole organisms due to their fluorescent properties. Imaging techniques based on
      detection of fluorescence can be used not only for observation of drug
      interaction with tumor cells, but also for targeting therapy of tumors with
      nanoparticles containing anthracycline cytostatics. Doxorubicin and daunorubicin,
      enclosed in liposomes, as representatives of nanoparticles suitable for targeted
      therapy, are used in clinical practice. The main advantage of liposomal drugs is
      to reduce the side effects due to differences in pharmacokinetics and
      distribution of the drug in the body. Due to the fact that all biological
      mechanisms of action of anthracycline drugs are not still fully understood,
      modern imaging techniques offer tool for in vivo studies of these mechanisms.

PMID- 23961854
TI  - [Contemporary trends of the adjutant chemotherapy in non-small cell lung cancer].
AB  - BACKGROUND: Adjuvant chemotherapy became a standard of treatment in completely
      resected non-small cell lung cancer (NSCLC) based on results of big trials meta
      analyses, which proved its influence on the decrease of relative mortality risk
      and absolute improvement of survival. Adjuvant chemotherapy is routinely used
      according to tumor stage evaluation, performance status (PS) and age of the
      patients. It is indicated in stage II and IIIA of NSCLC- in frame of clinical
      studies also in stage IB, in PS 0-1 and in patients under 75 years. Therapy with
      cisplatin and vinorelbine is a preferred regimen, as well as other drugs, such as
      paclitaxel, docetaxel, gemcitabine and pemetrexed. The problem is a relatively
      small dose intensity applied, due to toxic side effects. AIM: The present work is
      evaluating contemporary trends of adjuvant therapy in NSCLC according to latest
      clinical studies, which are finished or running. Efforts are directed to the
      improvement of treatment effectiveness, decrease of side effects and refinement
      of patients selection. Potential treatment benefit of better tolerable
      carboplatin is verified and results of trials with biologically targeted therapy
      are expected. Large clinical studies are evaluating the effect of tyrosine kinase
      inhibitors and angiogenesis inhibitors used either in various combinations with
      chemotherapy or as monotherapy. Application of vaccines is tested. CONCLUSION:
      Contemporary trend of adjuvant therapy is leading to the appropriate patient
      selection with regard to analysis of several prognostic and predictive
      biomarkers; it is proposed that future adjuvant therapy will be more and more
      personalized.

PMID- 23961855
TI  - [Degradation of proteins by ubiquitin proteasome pathway].
AB  - All intracellular and some extracellular proteins are continually degraded and
      replaced by synthesis of new proteins. Both these processes need to stay in
      equilibrium since their balance may lead to emergence of diseases. Cells contain
      many proteolytic systems that ensure highly specific and controlled degradation
      of proteins. One of these systems is the proteasome, a very complex molecular
      engine allowing degradation of proteins conjugated to ubiquitin. Since the first
      isolation of proteasome in 1968, many details about its function have been
      uncovered. In 2004, Nobel Prize for chemistry was awarded for these discoveries.
      In our review article, we aimed to summarize information about the mechanism of
      highly selective degradation of proteins by the ubiquitin proteasome pathway.
      Individual parts of the paper summarize current knowledge about highly selective
      degradation of proteins by the ubiquitin proteasome system, mechanisms of protein
      degradation regulation and bio-logical effects of proteasome inhibitors.

PMID- 23961856
TI  - [Pancreatic cancer and lifestyle factors].
AB  - BACKGROUND: Pancreatic cancer is a serious cancer with unfavorable prognosis. Due
      to differences in the incidence of pancreatic cancer in different regions, it is
      clear that factors associated with lifestyle play an important role in the
      etiology. The aim of this study was to evaluate the impact of selected lifestyle
      factors in relation to pancreatic cancer. MATERIALS AND METHODS: The study
      included a total of 529 subjects, including 309 cases and 220 control subjects.
      Cases of newly diagnosed patients with pancreatic cancer who lived in the region
      were selected in hospitals in three centers (University Hospital Olomouc,
      University Hospital Ostrava, Hospital Ceske Budejovice). The control group was
      obtained in cooperation with selected general practitioners for adults, and it is
      a population control group. RESULTS: Analyses compared persons who reported
      consuming alcohol with those who do not consume alcohol. Results showed a
      statistically significant inverse association, even after adjustment for the
      other studied factors (OR = 0.57, 95% CI 0.36 to 0.89). When assessing leisure
      time physical activity, results showed statistically significant inverse
      association and 35% decrease in the risk (crude OR = 0.65, 95% CI 0.45 to 0.93),
      and this inverse association was confirmed after adjustment for other studied
      factors although the result is on the border of statistical significance
      (adjusted OR = 0.68, 95% CI 0.44 to 1.04). Drinking coffee and tea has only a
      marginal impact on the occurrence of pancreatic cancer, although the medium and
      high consumption of black tea was found increased risk by 90 or 44%,
      respectively. Smoking is considered a causal risk factor for pancreatic cancer,
      but in this study, a positive association was not found. The study found no
      statistically significant association between overweight and obesity. CONCLUSION:
      Physical activity, dietary measures that will lead to weight loss and education
      to non-smoking can have a significant impact on the primary prevention of cancer.

PMID- 23961857
TI  - [Chromosome banding analysis of peripheral blood lymphocytes stimulated with IL2
      and CpG oligonucleotide DSP30 in patients with chronic lymphocytic leukemia].
AB  - BACKGROUND: Chromosomal aberrations play an important role as prognostic factors
      in chronic lymphocytic leukemia (CLL). These aberrations are mostly detected by
      fluorescent in situ hybridization (FISH), as chromosomal banding analysis has
      been scarce due to low proliferative activity of malignant B-lymphocytes in
      vitro. In 2006, a new method using stimulation with IL-2 and CpG oligonucleotide
      DSP30 for metaphase generation in CLL was published [1]. The objective of our
      study was to verify the efficacy of stimulation and to evaluate if the method is
      suitable for routine diagnostics. PATIENTS AND METHODS: In total, peripheral
      blood samples of 369 CLL patients were analyzed in parallel by chromosomal
      banding analysis and by FISH probes for 13q14, 11q22-23, CEP12 and 17p13.
      RESULTS: Out of 369 patients, 307 (83%) were successfully stimulated for
      metaphase generation. Chromosomal aberrations were detected in 243 (79%) out of
      307 patients evaluated by chromosomal banding analysis. Other aberrations that
      are not included into standard FISH panel were detected in patients karyotypes,
      e.g. del(6q), del(14q), t(14;18)(q32;q21), t(11;14)(q13;q32) and
      t(18;22)(q21;q11). One hundred and three (42%) patients showed complex aberrant
      karyotype not detected by FISH analysis. CONCLUSION: Stimulation with IL-2 and
      oligonucleotide DSP30 is an efficient method how to induce proliferation of
      malignant B-lymphocytes and allows detection of a substantial number of
      chromosomal aberrations in addition to those detected by standard FISH panel.
      Using this method in routine diagnostics is helpful particularly in
      identification of patients with complex aberrant karyotype.

PMID- 23961858
TI  - [Registry of neuroendocrine tumors (NET) in Czech Republic after three years of
      data collection].
AB  - BACKGROUND: Neuroendocrine tumors are traditionally considered to be "rare"
      diseases. On contrary, the prevalence of neuroendocrine tumors is high.
      Therefore, the diagnostics, treatment and follow-up of neuroendocrine tumors are
      subjected to an evolving interest. There are various specifics of neuroendocrine
      tumors requiring an appropriate feedback of each intervention i.e. data
      collection and central data evaluation. The "Cooperative Group for Neuroendocrine
      Tumors" (KSPNN) has been conducting a nationwide neuroendocrine tumors registry
      since June 2009. The first data summary after three years is aimed at evaluation
      of feasibility and data utility. MATERIAL AND METHODS: The anonymous data on
      diagnostics, therapy and follow up of patients with neuroendocrine tumors of any
      primary site are collected in the registry. The contribution is conditioned by
      morphologically proven diagnosis according to the current WHO 2010
      classification, in earlier cases WHO 2000 classification. The registry is
      operated by the Institute of Biostatistics and Analyses, Masaryk University
      (Brno). The initial analysis includes data from June 2009 to October 2012.
      RESULTS: Data of a substantial share of neuroendocrine tumor carriers have been
      collected -  742 subjects with a valid record, i.e. about 14% of presumed
      prevalence. Moreover, the registry covers nearly one fourth of incidence in the
      period 2009- 2011. The morphological diagnoses with the sign of nonspecific
      "neuroendocrine tumors" comprise the majority of records (75%); the most frequent
      is "carcinoid tumor neuroendocrine tumors". This results in a clear requirement
      for more detailed specifications of morphology as well as separation of small
      cell (neuroendocrine) carcinoma possessing principal bio-logic differences to
      neuroendocrine tumors itself. There is an apparent polarity of recorded clinical
      stages. Both stage I and stage IV comprise 30% of the records. This result is
      presumably related to how the diagnosis is established, either early and
      incidentally in initial stage or late with a developed endocrine symptomatology,
      in advanced stage. There is an evident selection bias. The treatment data reflect
      current trends, dominance of surgical therapy including reasonable cytoreductive
      surgery, vast use of somatostatine analogues in advanced disease and persistent
      position of chemotherapy for high grade tumors. The distribution of treatment
      modalities in the records documents a certain adherence to international
      treatment standards (ENETS, ESMO, NCCN). CONCLUSION: The dynamics of data
      contributions confirm feasibility of data collection in the registry. The
      registry reveals a clear requirement for more detailed analyses of biopsies and
      more detailed disease morphology classification. In the near future, the registry
      is aimed to maintain the increasing volume of collected data and to cover the
      majority of neuroendocrine tumors incidence.

PMID- 23961859
TI  - Synchronous bilateral testicular germ cell tumour: case report and review of the
      literature.
AB  - We report a case of a 30 years old male affected by synchronous bilateral germ
      cell tumor with a history of unilateral cryptorchidism; the patient underwent
      surgical treatment followed by adjuvant radiotherapy on paraaortic and iliac
      lymphnodes. Patients with synchronous tumors usually present with a higher stage
      disease in contrast to those with unilateral testicular carcinoma, yet the
      prognosis remains equally favorable.

PMID- 23961860
TI  - [Is the same tyrosine kinase inhibitor still effective after development of brain
      metastases? A Case report].
AB  - There is a new era of treatment options since introduction of new biological
      targeted therapies (tyrosine kinase inhibitors (TKIs) and mammalian target of
      rapamycin (mTOR) inhibitors) in renal cell cancer. However, in patients who
      developed brain metastases, there is still treatment dilemma about an optimal
      therapeutic scenario, particularly in the subgroup of patients with-out disease
      progression outside the central nervous system. The objective of this case report
      is to present that it is possible to continue the same targeted therapy after
      development of brain metastasis after application of local whole brain
      irradiation with meaningful overall survival.

PMID- 23961863
TI  - Giant metastatic testicular tumor.

PMID- 23961864
TI  - A model of corticostriatal plasticity for learning oculomotor associations and
      sequences.
AB  - We present models that learn context-dependent oculomotor behavior in (1)
      conditional visual discrimination and (2) sequence reproduction tasks, based on
      the following three principles: (1) Visual input and efferent copies of motor
      output produce patterns of activity in cortex. (2) Cortex influences the saccade
      system in part via corticostriatal projections. (3) A reinforcement learning
      mechanism modifies corticostriatal synapses to link patterns of cortical activity
      to the correct saccade responses during trial-and-error learning. Our conditional
      visual discrimination model learns to associate visual cues with the
      corresponding saccades to one of two left-right targets. A visual cue produces
      patterns of neuronal activity in inferotemporal cortex (IT) that projects to the
      oculomotor region of the striatum. Initially random saccadic "guesses," when
      directed to the correct target for the current cue, result in increased synaptic
      strength between the cue-related IT cells and the striatal cells that participate
      in the correct saccade, increasing the probability that this cue will later
      elicit the correct saccade. We show that the model generates "inhibitory
      gradients" on the striatum as the substrate for spatial generalization. Our
      sequence reproduction model learns, when presented with temporal sequences of
      spatial targets, to reproduce the corresponding sequence of saccades. At any
      point in the execution of a saccade sequence, the current pattern of activity in
      pre-frontal cortex (PFC), combined with visual input and the motor efferent copy
      of the previous saccade, produces a new pattern of activity in PFC to be
      associated with the next saccade. Like IT, PFC also projects to the oculomotor
      region of the striatum. Correct guesses for the subsequent saccade in the
      sequence results in strengthening of corticostriatal synapses between active PFC
      cells and striatal cells involved in the correct saccade. The sequence is thus
      reproduced as a concatenation of associations. We compare the results of this
      model with data previously obtained in the monkey and discuss the nature of
      cortical representations of spatiotemporal information. 

PMID- 23961865
TI  - Spatial versus Object Working Memory: PET Investigations.
AB  - We used positron emission tomography (PET) to answer the following question: Is
      working memory a unitary storage system, or does it instead include different
      storage buffers for different kinds of information? In Experiment 1, PET measures
      were taken while subjects engaged in either a spatial-memory task (retain the
      position of three dots for 3 sec) or an object-memory task (retain the identity
      of two objects for 3 sec). The results manifested a striking double dissociation,
      as the spatial task activated only right-hemisphere regions, whereas the object
      task activated primarily left-hemisphere regions. The spatial (right-hemisphere)
      regions included occipital, parietal, and prefrontal areas, while the object
      (left-hemisphere) regions included inferotemporal and parietal areas. Experiment
      2 was similar to Experiment 1 except that the stimuli and trial events were
      identical for the spatial and object tasks; whether spatial or object memory was
      required was manipulated by instructions. The PET results once more showed a
      double dissociation, as the spatial task activated primarily right-hemisphere
      regions (again including occipital, parietal and prefrontal areas), whereas the
      object task activated only left-hemisphere regions (again including
      inferotemporal and parietal areas). Experiment 3 was a strictly behavioral study,
      which produced another double dissociation. It used the same tasks as Experiment
      2, and showed that a variation in spatial similarity affected performance in the
      spatial but not the object task, whereas a variation in shape similarity affected
      performance in the object but not the spatial task. Taken together, the results
      of the three experiments clearly imply that different working-memory buffers are
      used for storing spatial and object information. 

PMID- 23961866
TI  - PET Studies of Auditory and Phonological Processing: Effects of Stimulus
      Characteristics and Task Demands.
AB  - Positron emission tomography (PET) was used to investigate the functional anatomy
      of auditory and phonological processing. Stimulus sets were designed to determine
      areas of the brain significantly activated during speech and nonspeech acoustic
      processing for stimuli with or without rapidly changing acoustic cues.
      Performance of auditory target detection tasks using these stimulus sets produced
      increased activation in superior temporal, frontal opercular, and medial frontal
      (SMA) cortices, relative to a visual fixation control task. While the medial
      frontal and superior temporal changes are best explained by motor and sensory
      components of the task, respectively, the frontal opercular changes were
      dependent upon the task performed upon the auditory input (mere presentation of
      the stimuli did not result in significant activation). On the left, the frontal
      opercular increases were larger when subjects performed an auditory detection
      task upon stimuli that incorporated rapid temporal changes (words, syllables, and
      tone sequences) than steady-state vowels. A converging study involving
      performance of orthographic (ascending letter) and phonological (long vowel
      sound) word discrimination tasks supports anatomical and behavioral evidence
      suggesting the left frontal opercular region is important for certain types of
      auditory/temporal analysis, as well as high-level articulatory coding. In
      addition to the activation increases associated with performance of auditory
      target detection tasks, decreases in activation were observed bilaterally along
      the intraparietal sulcus and superior parietal cortex, in the Rolandic sulcus,
      and the posterior cingulate; these decreases may reflect an attentional shift
      away from areas involved in the fixation task during the performance of a
      difficult auditory task. These results demonstrate that focusing more closely on
      basic neural processing differences (such as temporal integration rates) may lead
      to a better understanding of the specific neural processes that underlie complex
      phonological tasks. 

PMID- 23961867
TI  - Who Did What and When? Using Word- and Clause-Level ERPs to Monitor Working
      Memory Usage in Reading.
AB  - ERPs were recorded from 24 undergraduates as they read sentences known to differ
      in syntactic complexity and working memory requirements, namely Object and
      Subject Relative sentences. Both the single-word and multiword analyses revealed
      significant differences due to sentence type, while multiword ERPs also showed
      that sentence type effects differed for Good and Poor comprehenders. At the
      single-word level, ERPs to both verbs in Object Relative sentences showed a left
      anterior negativity between 300 and 500 msec postword-onset relative to those to
      Subject Relative verbs. At the multiword level, a slow frontal positivity
      characterized Subject Relative sentences, but was absent for Object Relatives.
      This slow positivity appears to index ease of processing or integration. and was
      more robust in Good than in Poor comprehenders. 

PMID- 23961868
TI  - Representation of grammatical categories of words in the brain.
AB  - We report the performance of a patient who, as a consequence of left frontal and
      temporoparietal strokes, makes far more errors on nouns than on verbs in spoken
      output tasks, but makes far more errors on verbs than on nouns in written input
      tasks. This double dissociation within a single patient with respect to
      grammatical category provides evidence for the hypothesis that phonological and
      orthographic representations of nouns and verbs are processed by independent
      neural mechanisms. Furthermore, the opposite dissociation in the verbal output
      modality, an advantage for nouns over verbs in spoken tasks, by a different
      patient using the same stimuli has also been reported (Caramazza & Hillis, 1991).
      This double dissociation across patients on the same task indicates that results
      cannot be ascribed to "greater difficulty" with one type of stimulus, and
      provides further evidence for the view that grammatical category information is
      an important organizational principle of lexical knowledge in the brain. 

PMID- 23961870
TI  - Image and brain: the resolution of the imagery debate.

PMID- 23961869
TI  - Interview with daniel C. Dennett.
AB  - Daniel Dennett was educated at Harvard and Oxford, receiving his D.Phil. in 1965.
      After six years at University of California Irvine, he moved to Tufts, where he
      is Distinguished Professor of Arts and Sciences and Director of the Center for
      Cognitive Studies. It is the author of articles on many issues in artificial
      intelligence, psychology, and cognitive ethology, as well as in philosophy. His
      books are Content and Consciousness (1969), Brainstorms (1978), The Mind's I
      (with Douglas Hofstadter, 1981). Elbow Room (1984), The Intentional Stance
      (1987), and Consciousness Explained (1991). His new book, Darwin's Dangerous
      Idea, will be published by Simon & Schuster in spring, 1995. 

PMID- 23961871
TI  - Contrast sensitivity.

PMID- 23961872
TI  - Synaptic plasticity-molecular, cellular, and functional aspects.

PMID- 23961873
TI  - Erratum.

PMID- 23961874
TI  - Cryopreservation of glucose-6-phosphate dehydrogenase activity inside red blood
      cells: developing a specimen repository in support of development and evaluation
      of glucose-6-phosphate dehydrogenase deficiency tests.
AB  - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human
      enzyme deficiency. It is characterized by abnormally low levels of G6PD activity.
      Individuals with G6PD deficiency are at risk of undergoing acute haemolysis when
      exposed to 8-aminoquinoline-based drugs, such as primaquine. For this reason it
      is imperative to identify individuals with G6PD deficiency prior to administering
      these anti-malarial drugs. There is a need for the development and evaluation of
      point-of-care G6PD deficiency screening tests suitable for areas of the
      developing world where malarial treatments are frequently administered. The
      development and evaluation of new G6PD tests will be greatly assisted with the
      availability of specimen repositories. METHODS: Cryopreservation of erythrocytes
      was evaluated as a means to preserve G6PD activity. Blood specimens from 31
      patients including ten specimens with normal G6PD activity, three with
      intermediate activity, and 18 with deficient activity were cryopreserved for up
      to six months. RESULTS: Good correlation in G6PD activity between fresh and
      cryopreserved specimens (R2 = 0.95). The cryopreserved specimens show an overall
      small drop in mean G6PD activity of 0.23 U/g Hb (P=0.23). Cytochemical staining
      showed that intracellular G6PD activity distribution within the red blood cell
      populations is preserved during cryopreservation. Furthermore, the mosaic
      composition of red blood cells in heterozygous women is also preserved for six
      months or more. The fluorescent spot and the BinaxNOW qualitative tests for G6PD
      deficiency also showed high concordance in G6PD status determination between
      cryopreserved specimens and fresh specimens. CONCLUSIONS: A methodology for
      establishing a specimen panel for evaluation of G6PD tests is described. The
      approach is similar to that used in several malaria research facilities for the
      cryopreservation of parasites in clinical specimens and axenic cultures.
      Specimens stored in this manner will aid both the development and evaluation of
      current and emerging G6PD tests. The availability of G6PD tests is a critical
      bottleneck to broader access to drugs that confer radical cure of Plasmodium
      vivax, a requirement for elimination of malaria.

PMID- 23961875
TI  - Promoter methylation patterns in Richter syndrome affect stem-cell maintenance
      and cell cycle regulation and differ from de novo diffuse large B-cell lymphoma.
AB  - In a fraction of patients, chronic lymphocytic leukaemia (CLL) can transform to
      Richter syndrome (RS), usually a diffuse large B-cell lymphoma (DLBCL). We
      studied genome-wide promoter DNA methylation in RS and clonally related CLL
      phases of transformed patients, alongside de novo DLBCL (of non-germinal centre B
      type), untransformed-CLL and normal B-cells. The greatest differences in global
      DNA methylation levels were observed between RS and DLBCL, indicating that these
      two diseases, although histologically similar, are epigenetically distinct. RS
      was more highly methylated for genes involved in cell cycle regulation. When RS
      was compared to the preceding CLL-phase and with untransformed-CLL, RS presented
      a higher degree of methylation for genes possessing the H3K27me3 mark and PRC2
      targets, as well as for gene targets of TP53 and RB1. Comparison of the
      methylation levels of individual genes revealed that OSM, a stem cell regulatory
      gene, exhibited significantly higher methylation levels in RS compared to CLL
      phases. Its transcriptional repression by DNA methylation was confirmed by 5-aza
      2'deoxycytidine treatment of DLBCL cells, determining an increased OSM
      expression. Our results showed that methylation patterns in RS are largely
      different from de novo DLBCL. Stem cell-related genes and cell cycle regulation
      genes are targets of DNA methylation in RS. 

PMID- 23961876
TI  - Large molecular weight nitroxide biradicals providing efficient dynamic nuclear
      polarization at temperatures up to 200 K.
AB  - A series of seven functionalized nitroxide biradicals (the bTbK biradical and six
      derivatives) are investigated as exogenous polarization sources for dynamic
      nuclear polarization (DNP) solid-state NMR at 9.4 T and with ca. 100 K sample
      temperatures. The impact of electron relaxation times on the DNP enhancement
      (epsilon) is examined, and we observe that longer inversion recovery and phase
      memory relaxation times provide larger epsilon. All radicals are tested in both
      bulk 1,1,2,2-tetrachloroethane solutions and in mesoporous materials, and the
      difference in epsilon between the two cases is discussed. The impact of the
      sample temperature and magic angle spinning frequency on epsilon is investigated
      for several radicals each characterized by a range of electron relaxation times.
      In particular, TEKPol, a bulky derivative of bTbK with a molecular weight of 905
      g.mol(-1), is presented. Its high-saturation factor makes it a very efficient
      polarizing agent for DNP, yielding unprecedented proton enhancements of over 200
      in both bulk and materials samples at 9.4 T and 100 K. TEKPol also yields
      encouraging enhancements of 33 at 180 K and 12 at 200 K, suggesting that with the
      continued improvement of radicals large epsilon may be obtained at higher
      temperatures. 

PMID- 23961877
TI  - Short-term effects of neoadjuvant chemoradiation therapy on anorectal function in
      rectal cancer patients: a pilot study.
AB  - BACKGROUND: Neoadjuvant chemoradiation therapy followed by curative surgery has
      gained acceptance as the therapy of choice in locally advanced rectal cancer.
      However, deterioration of anorectal function after long-course neoadjuvant
      chemoradiation therapy combined with surgery for rectal cancer is poorly defined.
      The aim of this study was to evaluate the physiological and clinical change of
      anorectal function after neoadjuvant chemoradiation therapy for rectal cancer.
      METHODS: We analyzed 30 patients on whom preoperative anorectal manometry data
      were available both before and after chemoradiation from October 2010 to
      September 2011. All patients underwent long-course neoadjuvant chemoradiation
      therapy. We compared manometric parameters between before and after neoadjuvant
      chemoradiation therapy. RESULTS: Of 30 patients, 20 were males and 10 females.
      The mean age was 64.9 +/- 9.9 years (range, 48-82). Before nCRT, the rectal
      compliance was higher in patients with ulceroinfiltrative type (P = 0.035) and
      greater involvement of luminal circumference (P = 0.017). However, there was the
      tendency of increased rectal sensory threshold for desire to defecate when the
      patient had decreased circumferential ratio of the tumor (P = 0.099), down-graded
      T stage (P = 0.016), or reduced tumor volume (P = 0.063) after neoadjuvant
      chemoradiation. CONCLUSIONS: Neoadjuvant chemoradiation therapy did not
      significantly impair overall sphincter function before radical operation. The
      relationship between tumor response of chemoradiation and sensory threshold for
      desire to defecate may suggest that neoadjuvant chemoradiation may be helpful for
      defecatory function as well as local disease control, at least in the short-term
      period after the radiation in locally advanced rectal cancer patients.

PMID- 23961878
TI  - Identification and optimization of pteridinone Toll-like receptor 7 (TLR7)
      agonists for the oral treatment of viral hepatitis.
AB  - Pteridinone-based Toll-like receptor 7 (TLR7) agonists were identified as potent
      and selective alternatives to the previously reported adenine-based agonists,
      leading to the discovery of GS-9620. Analogues were optimized for the
      immunomodulatory activity and selectivity versus other TLRs, based on
      differential induction of key cytokines including interferon alpha (IFN-alpha)
      and tumor necrosis factor alpha (TNF-alpha). In addition, physicochemical
      properties were adjusted to achieve desirable in vivo pharmacokinetic and
      pharmacodynamic properties. GS-9620 is currently in clinical evaluation for the
      treatment of chronic hepatitis B (HBV) infection. 

PMID- 23961879
TI  - Additional value of lateral tissue Doppler imaging in the assessment of diastolic
      dysfunction among subjects with pseudonormal pattern of mitral inflow.
AB  - BACKGROUND: There has been a lack of research on further stratification of
      subjects who have pseudonormal pattern of mitral inflow. The study aim was to
      clarify 2 different groups with different diastolic function grades among these
      subjects using lateral tissue Doppler imaging (TDI). METHODS: A total of 122
      consecutive subjects showing pseudonormal pattern of mitral inflow (E/A >= 1 and
      septal e'/a' < 1) without structural abnormality were prospectively recruited.
      TDI measurements were performed from both septal and lateral mitral annuli.
      RESULTS: Study subjects were stratified according to lateral TDI pattern (e'/a' <
      1 [n = 50] versus e'/a' >= 1 [n = 72]). Subjects with lateral e'/a' < 1 had
      higher values of left atrial volume index (LAVI) and E/e' compared to those for
      lateral e'/a' >= 1 (p < 0.001 for each). Among subjects with lateral e'/a' >= 1,
      only 9.3% of subjects had grade II diastolic dysfunction, whereas among subjects
      with lateral e'/a' < 1, majority of subjects (64.1%) had grade II diastolic
      dysfunction (p < 0.001). Multiple linear regression analysis showed that lateral
      e'/a' was independently associated with LAVI (beta = -0.484, p < 0.001), even
      after adjusting for potential confounders including age, sex, body mass index,
      hypertension and diabetes. CONCLUSIONS: In subjects without structural
      abnormality showing E/A >= 1 and septal e'/a' < 1, lateral TDI measurement is
      useful in the assessment of diastolic dysfunction. Lateral e'/a' >= 1 is a
      valuable indicator of early diastolic dysfunction but not of advanced diastolic
      dysfunction in this population.

PMID- 23961881
TI  - Causes of death in a cohort treated for opioid dependence between 1985 and 2005.
AB  - AIMS: To examine changes in causes of death in a cohort treated for opioid
      dependence, across time and age; quantify years of potential life lost (YPLL);
      and identify avoidable causes of death. DESIGN: People in New South Wales (NSW)
      who registered for opioid substitution therapy (OST), 1985-2005, were linked to a
      register of all deaths in Australia. SETTING: NSW, Australia. MEASUREMENTS: Crude
      mortality rates (CMRs), age-sex-standardized mortality rates (ASSRs) and
      standardized mortality ratios (SMRs) across time, sex and age. Years of potential
      life lost (YPLL) were calculated with reference to Australian life tables and by
      calculating years lost before the age of 65 years. FINDINGS: There were 43 789
      people in the cohort, with 412 216 person-years of follow-up. The proportion of
      the cohort aged 40+ years increased from 1% in 1985 to 39% in 2005. Accidental
      opioid overdoses, suicides, transport accidents and violent deaths declined with
      age; deaths from cardiovascular disease, liver disease and cancer increased.
      Among men, 89% of deaths were potentially avoidable; among women, 86% of deaths
      were avoidable. There were an estimated 160 555 YPLL in the cohort, an average of
      44 YPLL per decedent and an average of 29 YPLL before age 65 years. CONCLUSIONS:
      Among a cohort of opioid-dependent people in New South Wales, 1985-2005, almost
      nine in 10 deaths in the cohort were avoidable. There is huge scope to improve
      mortality among opioid-dependent people.

PMID- 23961882
TI  - Perceptions of obstetrical interventions and female genital cutting: insights of
      men in a Somali refugee community.
AB  - OBJECTIVES: Somali women are at increased risk of adverse pregnancy outcomes.
      Anxiety and perceived stigmatization toward female genital cutting (FGC) further
      fuels an atmosphere of miscommunication and distrust, contributing to poorer
      health outcomes. While the attitudes and experiences of Somali refugee women
      toward healthcare are widely known, the views of Somali refugee men are largely
      unknown. This study examines the perspectives of Somali men toward FGC and
      women's childbirth experiences in one refugee community in the USA. DESIGN:
      Community-based participatory research partnerships with key stakeholders within
      the Somali refugee community incorporated qualitative methods comprising semi
      structured focus groups and individual interviews to elicit male participants'
      perspectives on FGC, experiences during childbirth, and the perception of
      increased cesarean deliveries among Somali women. Qualitative analyses involved a
      framework and team-based approach using grounded theory and conventional content
      analysis. RESULTS: Acculturation influenced changes in traditional gender roles
      fostering new dynamics in shared decision-making within the household and during
      childbirth. Participants were aware of FGC-related morbidity, ongoing matriarchal
      support for FGC, and were generally not supportive of FGC. They perceived health
      care providers as being unfamiliar with caring for women with FGC fueling
      profound aversion to cesarean deliveries, miscommunication, and distrust of the
      health-care system. CONCLUSION: Our work yields new insights into Somali
      reproductive healthcare through Somali men, namely: strong matriarchal support of
      FGC, discomfort in men's presence during delivery, and a strong aversion to
      cesarean delivery. Our findings support the need for advocacy to engage Somali
      women, their partners/spouses, and health-care providers in facilitating greater
      continuity of care, building greater trust as men become engaged throughout the
      spectrum of care in the decision-making process while respecting traditional
      norms. Cultural health navigators should bridge communication and support between
      providers and patients. Our work provides foundational knowledge to inform
      culturally appropriate health interventions within a Somali refugee community.

PMID- 23961883
TI  - Treatment of children and adolescents with ulcerative colitis by adsorptive
      depletion of myeloid lineage leucocytes as monotherapy or in combination with low
      dose prednisolone after failure of first-line medications.
AB  - BACKGROUND: Currently available drugs for the treatment of ulcerative colitis
      (UC) include salicylates, thiopurines, corticosteroids and new anti-tumour
      necrosis factor (TNF)-alpha biologics. Among these medications, corticosteroids
      in children and adolescents may adversely affect the patients' growth and
      development. Further, UC patients have elevated and activated myeloid lineage
      leucocytes including the CD14 + CD16+ monocytes, which release TNF-alpha as a
      significant exacerbating factor. Accordingly, depletion of these cells by
      granulocyte/monocyte adsorption (GMA) should alleviate inflammation and promote
      UC remission. The objective of this study was to evaluate the efficacy of GMA in
      children and adolescents in whom conventional first-line medications had failed
      to induce remission. METHODS: In a single centre setting, between 2007 and 2012,
      a total of 24 consecutive children and adolescents, age 11-19 years were given
      mesalazine or sulphasalazine as a first-line medication. Seventeen patients
      relapsed or did not respond to the first-line medications, and received GMA with
      the Adacolumn, 2 sessions in the first week, and then weekly, up to 11 sessions.
      Patients who achieved a decrease of >=5 in the clinical activity index (CAI) were
      to continue with GMA, while non-responders were to receive 0.5 to 1.0 mg/kg/day
      prednisolone (PSL) plus additional GMA sessions similar to GMA responder cases.
      At entry and week 12, patients were clinically and endoscopically evaluated,
      allowing each patient to serve as her/his own control. RESULTS: Seven patients
      achieved remission with the first-line medications and did not receive GMA. Five
      patients did not respond to the first 5 GMA sessions and received PSL plus GMA,
      while 12 patients responded to the first 5 GMA sessions and received additional
      sessions. At entry, the average CAI was 12.7 +/- 2.5, range 8-17, and the average
      endoscopic index was 8.5 +/- 1.5, range 7-11. The corresponding values at week 12
      were 2.1 +/- 0.2, range 1-4 (P < 0.001) and 2.4 +/- 0.2, range 1-4 (P < 0.001).
      PSL was tapered to 0 mg within 3 months. CONCLUSIONS: With the strategy we
      applied in this study, all 24 consecutive patients achieved remission. In growing
      patients with active UC refractory to first-line medications, GMA was associated
      with clinical remission and mucosal healing, while in non-responders to GMA
      monotherapy, addition of a low dose PSL enhanced the efficacy of GMA and tapering
      of the PSL dose soon after remission was not associated with UC relapse.
      Therefore, the majority of young corticosteroid naive UC patients in whom first
      line salicylates have failed may respond to GMA and be spared from additional
      drug therapy. Avoiding corticosteroids at an early stage of UC should ensure
      better long-term clinical course.

PMID- 23961884
TI  - The metabolic acclimation of Arabidopsis thaliana to arsenate is sensitized by
      the loss of mitochondrial LIPOAMIDE DEHYDROGENASE2, a key enzyme in oxidative
      metabolism.
AB  - Mitochondrial lipoamide dehydrogenase is essential for the activity of four
      mitochondrial enzyme complexes central to oxidative metabolism. The reduction in
      protein amount and enzyme activity caused by disruption of mitochondrial
      LIPOAMIDE DEHYDROGENASE2 enhanced the arsenic sensitivity of Arabidopsis
      thaliana. Both arsenate and arsenite inhibited root elongation, decreased
      seedling size and increased anthocyanin production more profoundly in knockout
      mutants than in wild-type seedlings. Arsenate also stimulated lateral root
      formation in the mutants. The activity of lipoamide dehydrogenase in isolated
      mitochondria was sensitive to arsenite, but not arsenate, indicating that
      arsenite could be the mediator of the observed phenotypes. Steady-state
      metabolite abundances were only mildly affected by mutation of mitochondrial
      LIPOAMIDE DEHYDROGENASE2. In contrast, arsenate induced the remodelling of
      metabolite pools associated with oxidative metabolism in wild-type seedlings, an
      effect that was enhanced in the mutant, especially around the enzyme complexes
      containing mitochondrial lipoamide dehydrogenase. These results indicate that
      mitochondrial lipoamide dehydrogenase is an important protein for determining the
      sensitivity of oxidative metabolism to arsenate in Arabidopsis. 

PMID- 23961885
TI  - Reminiscence.
AB  - In order to refute the reported relationships between reminiscence and other
      organismic variables, Peters (1972) denies the existence of individual
      differences in reminiscence. His conclusions are based upon the factor analysis
      of Eysenck's (1960 a,b) data from a one-group study featuring multiple rests on a
      motor task. Present results from a traditionally designed single rest experiment
      indicate that the rest produces a reliable alteration in the pattern of
      individual differences. Criticisms of the single group, multiple rest design are
      offered along with some methodological suggestions for those who would relate
      individual differences in reminiscence to other organismic variables. 

PMID- 23961886
TI  - Differential effects of a foreperiod countdown procedure on simple and choice
      reaction time.
AB  - Subjects responded to the onset of a red or green stimulus light by pressing a
      key. In a simple reaction time (RT) block, they responded to the light onset
      without regard to its color. In a choice RT block, they pressed a left or right
      key depending on the stimulus color. Within each block, half of the trials were
      "countdown trials,"; i.e., a sequence of lights provided precise information
      concerning the passage of time during a constant 2-sec foreperiod. The other half
      of the trials involved the identical constant foreperiod, but no countdown
      information was presented. Data analysis revealed significantly faster reactions
      on countdown trials, with choice RT shortened more than simple RT. Results
      reflect subjects' imperfect timekeeping ability and suggest that readiness
      affects the central-processing phase of information processing. 

PMID- 23961887
TI  - Processing demands during movement.
AB  - Subjects made a speeded stylus movement along a track to a stop and
      simultaneously performed a simple reaction-time task designed to assess the
      processing demands of the movement task. Movement task variables were: (a) number
      of alternative ending positions - either one or two - with the choice executed
      during movement, and (b) presentation time for the endpoint signals in the two
      choice conditions, either prior to movement initiation (immediate) or during
      movement execution (delay). Processing demands were higher during all movement
      conditions than in a control condition that did not require movement. Processing
      demands during execution of the one-and two-choice movement with immediate
      signals did not differ. However, processing demands during the two-choice
      movements with delayed signals were higher than demands during the two-choice
      movement with immediate signals. 

PMID- 23961888
TI  - The effect of failure and the nature of the audience on performance of a complex
      motor task.
AB  - Social facilitation theory states that an audience functions as a conditioned
      stimulus for generalized drive and that this drive effect is learned through
      classical conditioning. In the present study an attempt was made to classically
      condition an aversive drive to an audience by having a subject fail a task in
      front of an audience. A sample of 72 subjects (12 per group) took part in a 3 * 2
      factorial design. Half of the subjects were exposed to failure in front of an
      audience on a first task. These subjects then performed a second complex motor
      task in front of the same audience who were described as either experts on this
      second task or as students who were interested in the task (non-expert audience).
      No differences in performance were found between those groups that had failed a
      first task and those that had not. However, significant differences in
      performance were found between the no-audience control, non-expert audience, and
      expert audience conditions. 

PMID- 23961889
TI  - A motor performance typology of boys and girls in the age range 6 to 10 years.
AB  - A motor performance typology of boys and girls (ages 6-10 years) was developed
      based on four factors extracted by factor analysis from data on 47 physical
      growth and motor performance variables. Nineteen variables which best described
      the four factor-defined components were used in formulating the person-clusters
      (typologies) following Tryon's condensation method. Eleven person-clusters
      emerged, which included 137 of the 146 children tested, or 95% of the group. The
      five personclusters that accounted for the majority of girls (73%) accounted for
      only 16% of the boys. The six person-clusters that accounted for the majority of
      boys (84%) accounted for only 27% of the girls. 

PMID- 23961890
TI  - The effects of task coherency, preview, and speed-stress on timing and
      anticipation.
AB  - High levels of skill displayed in perceptual-motor tasks can only be obtained by
      accurate timing and anticipation. Recent evidence indicates that task
      characteristics that change or alter the predictability of stimulus events are
      potent determiners of performance. The effects of stimulus predictability on
      timing and anticipation were investigated in a series of studies where subjects
      responded to moving stimuli that entered critical zones on each of three visual
      displays. Specific task characteristics that changed the predictability of the
      stimulus sequence and significantly affected performance in the studies included
      task coherency, preview, speed-, and load-stress. 

PMID- 23961891
TI  - The effect of unimanual performance on speed of verbalization.
AB  - Male college students (N = 20) named colors under two levels of difficulty while
      turning a wheel with one hand. The hand used was found to be unrelated to naming
      time. In a second experiment, 24 male college students performed a dowel
      balancing task while repeating a simple sentence and while remaining silent.
      Verbalization was found to be unrelated to hand used while dowel-balancing. The
      results failed to replicate and extend earlier findings. 

PMID- 23961892
TI  - The effect of overt rehearsal on motor short-term memory.
AB  - The effects of different types of rehearsal on the recall of a blind motor
      movement were explored. Immediate recall and delayed recall (covert rehearsal)
      were compared to recall after the overt rehearsal of either movement distance or
      end-location. Spontaneous decay was evident in a large increase in variable error
      (VE) for all rehearsal conditions even though the location cue was reliable.
      Massed distance rehearsals yielded less VE than spaced, and VE increased with
      successive rehearsals, providing further support for spontaneous decay. Constant
      error showed a central tendency effect and decreased in overshooting over time.
      Longer movements yielded more VE than shorter, and the increase in VE over time
      was greater for longer movements, suggesting that retention characteristics may
      differ as a function of movement length. 

PMID- 23961893
TI  - Experimenter Effects on Children's Motor Performance.
AB  - In order to evaluate the effects of the amount of previous experimenter-subject
      contact on two motor tasks, male and female subjects (N=75, aged 3-5 yr.) were
      assigned to one of five treatment conditions (zero, one, three, or five contact
      periods, or tested by the teacher). The design was counterbalanced so that the
      effects of experimenter sex could be determined. Experimenter effects were not
      shown in these motor performances, and neither the amount of previous
      experimenter-subject contact nor the subject's sex produced differences in motor
      performance. This result might be due to the type of motor task used as
      contrasted to the type of cognitive task in which experimenter effects are often
      noted. 

PMID- 23961894
TI  - A priori probability effects on simple reaction time.
AB  - Three factors - immediate foreperiod (1.0 and 4.0 sec), previous foreperiod (1.0
      and 4.0 sec) and a priori probability (0.8 and 0.2) - were employed in a variable
      foreperiod simple RT design. The possibility was examined that a priori
      probability functioned independently of the previous foreperiod effect, an
      hypothesis advanced as an explanation for the inverse relationship between simple
      RT and foreperiod length. This possibility was confirmed in the present
      investigation. In addition, the results supported the contention that it is what
      the subject knows, not what he does not know, which controls simple RT. 

PMID- 23961895
TI  - Food proteins from different allergen families sensitize Balb/c mice to family
      specific immune responses.
AB  - The classification of food allergens based on the structure and function of
      proteins contributes to the study of the relationship between bioinformatics and
      potential allergenicity of allergens. Food allergens always share sequence
      similarity with the allergens in the same allergen families. For that reason,
      food proteins from different allergen families may induce different patterns of
      immune responses in animal models. Female Balb/c mice (3-4-weeks-old) were
      sensitized with food proteins once per week for 4 weeks, and then challenged 2
      weeks later (on Day 42 of study). Blood was collected (to obtain serum levels of
      histamine and protein-specific IgG1 and IgE antibodies) and measures of vascular
      permeability were performed 20 min after the challenge. Five food proteins (11S
      globulin, OVA [ovalbumin], HAS [human serum albumin] and LRP [lysine-responsive
      storage protein] of different allergen families, and Cry 1Ab/Ac [crystal
      protein]) were used to assess patterns of immune responses for each allergen
      family and then bioinformatics and digestive stability in simulated gastric fluid
      were employed to assess the overall utility of the Balb/c. The assay results
      indicated that, in this model, histamine and protein-specific IgE antibody levels
      and vascular permeability could be used to identify allergenicity of 11S
      globulin, OVA, and PAP (potato acid phosphatase) only. However, the results of
      the protein-specific IgG1 measures could only distinguish allergic food proteins
      with negative control. Based on bioinformatic analyses, the five different food
      proteins clearly induced distinct patterns of immune responses in the Balb/c
      model.

PMID- 23961897
TI  - Analysis of duodenojejunal flexure formation in mice: implications for
      understanding the genetic basis for gastrointestinal morphology in mammals.
AB  - The mammalian gut undergoes morphological changes during development. We studied
      the developing mouse duodenojejunal flexure (DJF) to elucidate the mechanism of
      formation. During embryonic days 10.75-13.75, DJF formation was morphologically
      classified into three stages: the expansion stage, flexure formation stage, and
      flexure elongation stage. From the expansion to the flexure formation stages, the
      DJF wall showed asymmetric morphology and proliferation along the left-right
      intestinal axis. From the flexure formation to the flexure elongation stage, the
      DJF started to bend dorsally with counterclockwise rotation along the antero
      caudal intestinal axis, indicating that the original right side of the duodenum
      was rotated towards the dorsal body wall during development of the DJF. The
      direction of attachment of the dorsal mesentery to the DJF did not correspond to
      the bending direction of the DJF during flexure formation, and this finding
      indicated that the dorsal mesentery contributed very little to DJF formation.
      During DJF formation, Aldh1a2 and hedgehog mRNAs were detected at the DJF, and
      their expression levels differed along the bending axis. In conclusion, DJF
      formation might be triggered by asymmetric morphology and proliferation along the
      left-right intestinal axis under the control of retinoic acid and hedgehog
      signaling. 

PMID- 23961896
TI  - T-cell-dependent antibody responses in the rat: forms and sources of keyhole
      limpet hemocyanin matter.
AB  - The T-cell-dependent antibody response (TDAR) is a functional assay used in
      immunopharmacology and immunotoxicology to assess ability to mount an antibody
      response to immunization. Keyhole limpet hemocyanin (KLH) is extensively used as
      the immunogen of choice in non-clinical and clinical settings. Native KLH is
      comprised of high molecular weight (HMW; 4-8 MDa) assemblies of KLH subunit
      dimers (> 600-800 kDa). It is not known how the different forms (HMW vs subunit)
      and manufacturing processes (commercial sources) may impact the nature of anti
      KLH immune responses (e.g. magnitude and inter-animal variability). Anti-KLH IgM
      and IgG responses were studied in Sprague-Dawley rats immunized with different
      forms and commercial sources of KLH: 100 ug of HMW KLH from two different sources
      or subunit KLH from three different sources. Biophysical and biochemical analyses
      were conducted to characterize the KLH formulations. Anti-KLH IgM and IgG
      responses were measured using a proprietary indirect quantitative
      electrochemiluminescence immunoassay. The HMW KLH preparations showed a greater
      number of sub-visible particles (2-150 um size range) than the subunit KLH
      preparations. All HMW KLH and all subunit KLH were equivalent on SEC
      (hydrodynamic volume), PAGE (size and charge), and SDS-PAGE (molecular radius).
      Robust primary and secondary anti-KLH responses were detected for both sources of
      HMW KLH. The subunit KLH immunizations resulted in lower IgG and IgM responses
      compared to the HMW KLH, with the exception of Stellar Biotechnologies subunit
      KLH that produced both robust primary and secondary responses, which approached
      the HMW KLH responses. Inter-animal variability for IgM and IgG responses was
      lower with HMW KLH than with subunit KLH. In conclusion, different forms and
      commercial sources of KLH were associated with different magnitudes and inter
      animal variability in IgM and IgG responses, a critical finding to take into
      consideration when designing TDAR studies for robust immunotoxicology or
      immunopharmacology testing.

PMID- 23961898
TI  - Giant vascular eccrine spiradenoma mimicking calcifying epithelioma.

PMID- 23961899
TI  - Saturated hydrogen saline attenuates endotoxin-induced acute liver dysfunction in
      rats.
AB  - To determine the effect of saturated hydrogen saline on lipopolysaccharide (LPS)
      induced acute liver dysfunction, rats were divided into control, LPS, and LPS
      plus saturated hydrogen saline (LPS+H(2)) groups. Treatment with saturated
      hydrogen saline prolonged the median survival time and reduced liver dysfunction.
      Moreover, saturated hydrogen saline significantly reduced pathological
      alterations in liver tissues, the number of ballooned hepatocytes, serum tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-6 levels, and myeloperoxidase
      (MPO) and malondialdehyde (MDA) levels in liver tissues (P<0.05). Cell apoptosis
      was detected in liver tissues after LPS treatment, and attenuated by saturated
      hydrogen saline treatment. Saturated hydrogen saline also decreased
      phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated Jun
      kinase (p-JNK), nuclear factor-kappa B (NF-kappaB), and second mitochondria
      derived activator of caspase (Smac) levels, and increased p38 activation
      (P<0.05). Thus, saturated hydrogen saline may attenuate LPS-induced acute liver
      dysfunction in rats, possibly by reducing inflammation and cell apoptosis.
      Mitogen-activated protein kinase (MAPK), NF-kappaB, and Smac may contribute to
      saturated hydrogen saline-mediated liver protection. 

PMID- 23961900
TI  - Rational design of chemical ligands for selective mitochondrial targeting.
AB  - The rational design of molecules with selective intracellular targeting is a
      great challenge for contemporary chemistry and life sciences. Here, we
      demonstrate a rational approach to development of compartment-specific
      fluorescent dyes from the gamma-aryl substituted pentamethine family. These novel
      dyes exhibit an extraordinary affinity and selectivity for cardiolipin in inner
      mitochondrial membrane and possess excellent photostability, fluorescent
      properties, and low phototoxicity. Selective imaging of live and fixed
      mitochondria was achieved in various cell lines using nanomolar concentrations of
      these dyes. Their high localization specificity and low toxicity enables study of
      morphological changes, structural complexity, and dynamics of mitochondria
      playing a pivotal role in many pathological diseases. These far-red emitting dyes
      could also serve in a variety of biomedical applications. 

PMID- 23961901
TI  - Multivalency of non-peptide integrin alphaVbeta3 antagonist slows tumor growth.
AB  - Multivalency is a powerful strategy for achieving high-affinity molecular binding
      of compounds to increase their therapeutic potency or imaging potential. In our
      study, multivalent non-peptide integrin alphavbeta3 antagonists (IA) were
      designed for antitumor therapy. Docking and molecular dynamics were employed to
      explore the binding modes of IA monomer, dimer, and trimer. In silico, one IA
      unit binds tightly in the active site with similar pose to native ligand RGD and
      other parts of dimer and trimer contribute extra binding affinities by
      interacting with residues in vicinity of the original site. In vitro studies
      demonstrated that increasing valency results in increasing antiproliferative and
      antiorganizational effects against endothelial cells (HUVECs), and a much weaker
      effect on melanoma B16F10 cells. The antitumor efficacies of the IA multivalent
      compounds were evaluated in subcutaneous B16F10 melanoma tumor-bearing mice. At
      30 mg/kg dose, the mean masses of tumors harvested 18 days after inoculation were
      significantly reduced (p<10(-7)) by 36+/-9%, 49+/-8%, and 71+/-7% for the IA
      monomer, dimer, and trimer groups, relative to control. The importance of
      multivalency was demonstrated to be highly significant beyond the additive effect
      of the extra pharmacological sites (p=0.00011). These results suggest that the
      major target of these anti-alphavbeta3 compounds is the neovasculature rather
      than the cancer cells, and the success of a multivalent strategy depends on the
      details of the components and linker. This is the first integrin alphavbeta3
      multivalent ligand showing clear enhancement in antitumor effectiveness.

PMID- 23961902
TI  - Double Dissociation between Overt and Covert Face Recognition.
AB  - Some patients with face agnosia (prosopagnosia) caused by occipitotemporal damage
      produce discriminatory covert responses to the familiar faces that they fail to
      identify overtly. For example, their average skin conductance responses (SCRs) to
      familiar faces are significantly larger than average SCRs to unfamiliar faces. In
      this study we describe the opposite dissociation in four patients with bilateral
      ventromedial frontal damage: The patients recognized the identity of familiar
      faces normally, yet failed to generate discriminatory SCRs to those same familiar
      faces. Taken together, the two sets of results constitute a double dissociation:
      bilateral occipitotemporal damage impairs recognition but allows SCR
      discrimination, whereas bilateral ventromedial damage causes the opposite. The
      findings suggest that the neural systems that process the somatic-based valence
      of stimuli are separate from and parallel to the neural systems that process the
      factual, nonsomatic information associated with the same stimuli. 

PMID- 23961903
TI  - A positron emission tomography study of visual and mental spatial exploration.
AB  - We measured normalized regional cerebral blood flow (NrCBF) using positron
      emission tomography (PET) and oxygen-15-labeled water in eight young right-handed
      healthy volunteers selected as high-imagers. during 2 runs of 3 different
      conditions: 1, rest in total darkness 2; visual exploration of a map 3; mental
      exploration of the same map in total darkness. NrCBF images were aligned with
      individual magnetic resonance images (MRI), and NrCBF variations between pairs of
      measurements (N = 15) were computed in regions of interest having anatomical
      boundaries that were defined using a three-dimensional (3-D) reconstruction of
      each subject MRI. During visual exploration, we found bilateral activations of
      primary visual areas, superior and inferior occipital gyri, fusiform and lingual
      gyri, cuneus and precuneus, bilateral superior parietal, and angular gyri. The
      right lateral premotor area was also activated during this task while superior
      temporal gyri and Broca's area were deactivated. By contrast, mental exploration
      activated the right superior occipital cortex, the supplementary motor area, and
      the cerebellar vermis. No activation was observed in the primary visual area.
      These results argue for a specific participation of the superior occipital cortex
      in the generation and maintenance of visual mental images. 

PMID- 23961904
TI  - Rapid changes of optical parameters in the human brain during a tapping task.
AB  - Measures of parameters of the migration of near-infrared photons through the head
      (attenuation, or intensity, and time-of-flight, or delay) have been proposed as a
      way of assessing noninvasively and in a quasicontinuous fashion changes in the
      scattering and absorption properties of brain tissue. These, in turn, may reflect
      functional changes associated with behavioral tasks. To test this hypothesis, we
      measured changes of photon migration parameters from scalp locations proximal to
      the motor cortex from four human subjects, tapping at a rate of 0.8 Hz with their
      left or right hand, or with their left or right foot. Tapping produced both slow
      effects (requiring several seconds) and fast effects (tracking the tapping
      frequency). Slow effects were characterized by increase and delay of the light
      passing through the hemisphere contralateral to the tapping hand. Fast effects
      consisted of changes in the light delay during hand tapping. Monte Carlo
      simulations based on layer models of the brain indicated that fast effects are
      consistent with changes in deep layers of the head (presumably in the cortex),
      and that slow effects are consistent with either a shift of absorbing material
      toward deeper layers or a reduction in scattering. These results suggest that
      optical parameters can monitor rapid changes of brain activity, matching the
      contralateral organization of the motor cortex. 

PMID- 23961905
TI  - Cognitive and neural mechanisms underlying visual and semantic processing:
      implications from "optic aphasia".
AB  - We report detailed analyses of the performance of a patient, DHY, who as a
      consequence of strokes in the left occipital lobe and the periventricular white
      matter in the region of the spleniuni, showed severely impaired naming of visual
      stimuli despite spared recognition of visual stimuli and spared naming in other
      modalities. This pattern of performance-labeled "optic aphasia"-has been
      previously interpreted as support for the hypothesis that there are independent
      semantic systems, either a visual and a verbal semantic store (Beauvois, 1982;
      Lhermitte & Beauvois, 1973) or a right hemisphere and a left hemisphere semantic
      system (Coslett & Saffran, 1989, l092), which are "disconnected" in these
      patients. We provide evidence that DHY shows precisely the types of performance
      across a variety of verbal and visual tasks that have been used to support these
      claims of separate semantic systems: (1) good performance in naming to definition
      and naming objects presented for tactile exploration (which has been interpreted
      as evidence of spared verbal or left hemisphere semantic processing), and (2)
      good performance on various "semantic" tasks that do not require naming (which
      has been interpreted as access to spared visual or right hemisphere semantic
      processing). Nevertheless, when nonverbal semantic tasks were modified such that
      they required access to more detailed semantic information for accurate
      performance, DHY was Par less accurate, indicating that she did not access
      complete semantic information about objects in the visual modality. We argue that
      these data undermine the claim that cases of optic aphasia can be explained only
      by proposing multiple semantic systems. We propose an alternative account for
      this pattern of performance, within a model of visual object naming that
      specifies a single, modality-independent semantic system. We show that the
      performance of DHY and other "optic aphasic" patients can be explained by
      proposing a deficit in accessing a complete, modality-independent, lexical
      semantic representation from an intact stored, structural description of the
      object. We discuss the implications of these conclusions for claims about the
      neuroanatomical correlates of semantic and visual object processing. 

PMID- 23961906
TI  - A neural network simulation of hallucinated "voices" and associated speech
      perception impairments in schizophrenic patients.
AB  - The mechanism of hallucinated speech, a symptom commonly reported by
      schizophrenic patients, is unknown. The hypothesis that these hallucinations
      arise from pathologically altered working memory underlying speech perception was
      explored. A neural network computer simulation of contextually guided sequential
      word detection based on Elman (1990a,b) was studied. Pruning anatomic connections
      or reducing neuronal activation in working memory caused word "percepts" to
      emerge spontaneously (i.e., in the absence of external "speech inputs"), thereby
      providing a model of hallucinated speech. These simulations also demonstrated
      distinct patterns of word detection impairments when inputs were accompanied by
      varying levels of noise. In a parallel human study, the ability to shadow
      noisecontaminated, connected speech was assessed. Schizophrenic patients
      reporting hallucinated speech demonstrated a pattern of speech perception
      impairments similar to a simulated neural network with reduced anatomic
      connectivity and enhanced neuronal activation. Schizophrenic patients not
      reporting this symptom did not demonstrate these speech perception impairments.
      Neural network simulations and human empirical data, when considered together,
      suggested that the primary cause of hallucinated "voices" in schizophrenia is
      reduced neuroanatomic connectivity in verbal working memory. 

PMID- 23961907
TI  - Functional mapping of sequence learning in normal humans.
AB  - The brain localization of motor sequence learning was studied in normal subjects
      with positron emission tomography. Subjects performed a serial reaction time
      (SRT) task by responding to a series of stimuli that occurred at four different
      spatial positions. The stimulus locations were either determined randomly or
      according to a 6-element sequence that cycled continuously. The SRT task was
      performed under two conditions. With attentional interference from a secondary
      counting task there was no development of awareness of the sequence. Learning
      related increases of cerebral blood flow were located in contralateral motor
      effector areas including motor cortex, supplementary motor area, and putamen,
      consistent with the hypothesis that nondeclarative motor learning occurs in
      cerebral areas that control limb movements. Additional cortical sites included
      the rostral prefrontal cortex and parietal cortex. The SRT learning task was then
      repeated with a new sequence and no attentional interference. In this condition,
      7 of 12 subjects developed awareness of the sequence. Learning-related blood flow
      increases were present in right dorsolateral prefrontal cortex, right premotor
      cortex, right ventral putamen, and biparieto-occipital cortex. The right
      dorsolateral prefrontal and parietal areas have been previously implicated in
      spatial working memory and right prefrontal cortex is also implicated in
      retrieval tasks of verbal episodic memory. Awareness of the sequence at the end
      of learning was associated with greater activity in bilateral parietal, superior
      temporal, and right premotor cortex. Motor learning can take place in different
      cerebral areas, contingent on the attentional demands of the task. 

PMID- 23961908
TI  - Longterm potentiation, vol. 2.

PMID- 23961909
TI  - A dynamic systems approach to the development of cognition and action.

PMID- 23961910
TI  - The cognitive neurosciences.

PMID- 23961913
TI  - Trophic collapse.

PMID- 23961912
TI  - Heart failure patients' descriptions of participation in structured home care.
AB  - BACKGROUND: To strengthen the patient's position in health care, patient
      participation has been decreed in policy documents and legalizations. For
      patients suffering from heart failure, self-care is an important part of disease
      management and participation is crucial to succeed with this. OBJECTIVE: To
      examine how heart failure patients receiving structured home care described
      participation in the care. DESIGN: Qualitative study. SETTING AND PARTICIPANTS:
      Thirteen men and six women, aged between 63 and 90 years, were interviewed. The
      informants received structured home care at four home care units in Sweden. The
      interviews were analysed using qualitative content analysis. RESULTS: Five
      categories with associated subcategories describing participation in care were
      identified: communication between patients and health-care professionals (HCPs)
      including time and space for dialogue and exchange of care-related information,
      accessibility to care through awareness of the plan for home visits or
      feasibility to initiate home visits, active involvement in care by engaging in
      self-care and collaboration with HCPs, trustful relation with HCPs, with
      confidence in competence and individually adapted care, options for decision
      making, by making decisions or entrusting decisions. CONCLUSIONS: Patient
      participation could be strengthened through structured home care. Participation
      was facilitated when there was a balance between the patient's own preferences to
      influence care and the health-care professional's actions and values and the
      organization of care. Barriers to participation could depend on the health-care
      organization, lack of continuity and confidence in HCPs.

PMID- 23961914
TI  - Ranolazine: effects on ischemic heart.
AB  - Coronary artery disease is the major cause of mortality and morbidity in the
      industrialized countries; in the United States of America and in Europe, it is
      responsible for one of every six deaths per year. In the setting of ischemic
      heart disease, angina pectoris and chest pain, in particular, are the major
      causes of emergency department accesses. Angina pectoris is a clinical syndrome
      characterized by discomfort typically in the chest, neck, chin and left arm
      induced by physical exertion, emotional stress and cold and is relieved by rest
      or by taking of nitrates. The main targets of treatment of angina pectoris are to
      improve quality of life by reducing the frequency and the severity of symptoms,
      to increase functional capacity and to improve prognosis. Ranolazine is a recent
      antianginal drug with unique methods of action. It was approved by the US Food
      and Drug Administration in 2006 as add-on therapy in patients symptomatic for
      stable angina. With the inhibition of the late sodium current, Ranolazine
      protects against ion deregulation, prevents cellular calcium overload and the
      subsequent increase in diastolic tension without impacting heart rate and blood
      pressure. Short term clinical trials and patent research show that add on therapy
      with Ranolazine in patients with chronic stable angina significantly improves
      exercise duration, exercise time to angina and reduces the use of nitro
      glycerine. Long term clinical trials showed no significant differences in the
      rate of cardiovascular death and myocardial infarction in patients with non-ST
      segment elevation acute coronary syndromes but a reduction in terms of recurrent
      ischemia. Ranolazine is generally well tolerated and even if it increases the
      duration of QTc interval it is not associated with atrial and ventricular
      arrhythmias. Therefore Ranolazine represents a good therapeutic approach in
      patients with chronic stable angina still symptomatic, while on optimal anti
      ischemic therapy, or intolerant to traditional anti-ischemic drugs. 

PMID- 23961915
TI  - Identification of piggyBac-mediated insertions in Plasmodium berghei by next
      generation sequencing.
AB  - BACKGROUND: The piggyBac transposon system provides a powerful forward genetics
      tool to study gene function in Plasmodium parasites via random insertion
      mutagenesis and phenotypic screening. The identification of genotype of piggyBac
      mutants in the Plasmodium genome is thus an indispensable step in forward genetic
      analysis. Several PCR-based approaches have been used to identify the piggyBac
      insertion sites in Plasmodium falciparum and Plasmodium berghei, but all are
      tedious and inefficient. Next generation sequencing can produce large amounts of
      sequence data and is particularly suitable for genome-wide association studies.
      In this study, the Next generation sequencing technology was employed to
      efficiently identify piggyBac insertion sites in the genome of P. berghei.
      METHODS: Plasmodium berghei parasites were co-transfected with piggyBac donor and
      helper plasmids. Initially, the classical inverse PCR method was used to identify
      the existence of piggyBac insertions in the P. berghei genome. The whole genome
      of post-transfection parasites was subsequently sequenced with a PCR-free paired
      end module using the Illumina HiSeq sequencing system. The two distinct methods
      ('BLAST method' and 'SOAP method') were employed to identify piggyBac insertion
      sites in the P. berghei genome with Illumina sequencing data. All the identified
      piggyBac insertions were further tested by half-nested PCR. RESULTS: The inverse
      PCR method resulted in a very low yield of ten individual insertions identified.
      Conversely, 47 piggyBac insertions were identified from about 1 Gb of Illumina
      sequencing data via the two distinct analysis methods. The majority of identified
      piggyBac insertions were confirmed by half-nested PCR. In addition, 1,850 single
      nucleotide polymorphisms were identified through alignment of the Illumina
      sequencing data of the P. berghei ANKA strain used in this study with the
      reference genome sequences. CONCLUSION: This study demonstrates that a high
      throughput genome sequencing approach is an efficient tool for the identification
      of piggyBac-mediated insertions in Plasmodium parasites.

PMID- 23961917
TI  - Absolute monocyte count at diagnosis and survival in mantle cell lymphoma.

PMID- 23961916
TI  - How to deal with low-resolution target structures: using SAR, ensemble docking,
      hydropathic analysis, and 3D-QSAR to definitively map the alphabeta-tubulin
      colchicine site.
AB  - alphabeta-Tubulin colchicine site inhibitors (CSIs) from four scaffolds that we
      previously tested for antiproliferative activity were modeled to better
      understand their effect on microtubules. Docking models, constructed by
      exploiting the SAR of a pyrrole subset and HINT scoring, guided ensemble docking
      of all 59 compounds. This conformation set and two variants having progressively
      less structure knowledge were subjected to CoMFA, CoMFA+HINT, and CoMSIA 3D-QSAR
      analyses. The CoMFA+HINT model (docked alignment) showed the best statistics:
      leave-one-out q(2) of 0.616, r(2) of 0.949, and r(2)pred (internal test set) of
      0.755. An external (tested in other laboratories) collection of 24 CSIs from
      eight scaffolds were evaluated with the 3D-QSAR models, which correctly ranked
      their activity trends in 7/8 scaffolds for CoMFA+HINT (8/8 for CoMFA). The
      combination of SAR, ensemble docking, hydropathic analysis, and 3D-QSAR provides
      an atomic-scale colchicine site model more consistent with a target structure
      resolution much higher than the ~3.6 A available for alphabeta-tubulin.

PMID- 23961919
TI  - A quantitative definition of scaphoid union: determining the inter-rater
      reliability of two techniques.
AB  - BACKGROUND: Despite extensive literature supporting the use of computerized
      tomography (CT) scans in evaluating scaphoid fractures, there has not been a
      consensus on the methodology for defining and quantifying union. The purpose of
      this study was to test the inter-observer reliability of two methods of
      quantifying scaphoid union. METHODS: The CT scans of 50 non-operatively treated
      scaphoid fractures were reviewed by four blinded observers. Each was asked to
      classify union into one of three categories, united, partially united, or
      tenuously united, based on their general impression. Each reviewer then carefully
      analyzed each CT slice and quantified union based on two methods, the mean
      percentage union and the weighted mean percentage union. The estimated percentage
      of scaphoid union for each scan was recorded, and inter-observer reliability for
      both methods was assessed using a Bland-Altman plot to calculate the 95% limits
      of agreement. Kappa statistic was used to measure the degree of agreement for the
      categorical assessment of union. RESULTS: There was very little difference in the
      percentage of union calculated between the two methods (mean difference between
      the two methods was 1.2 +/- 4.1%), with each reviewer demonstrating excellent
      agreement between the two methods based on the Bland-Altman plot. The kappa score
      indicated very good agreement (Kappa = 0.80) between the consultant hand surgeon
      and the musculoskeletal radiologist, and good agreement (Kappa = 0.62) between
      the consultant hand surgeon and the hand fellow for the categorical assessment of
      union. CONCLUSIONS: This study describes two methods of quantifying and defining
      scaphoid union, both with a high inter-rater reliability. This indicates that
      either method can be reliably used, making it an important tool for both for
      clinical use and research purposes in future studies of scaphoid fractures,
      particularly those which are using union or time to union as their endpoint.
      LEVEL OF EVIDENCE: Diagnostic, level III.

PMID- 23961920
TI  - Human resource development for a community-based health extension program: a case
      study from Ethiopia.
AB  - INTRODUCTION: Ethiopia is one of the sub-Saharan countries most affected by high
      disease burden, aggravated by a shortage and imbalance of human resources,
      geographical distance, and socioeconomic factors. In 2004, the government
      introduced the Health Extension Program (HEP), a primary care delivery strategy,
      to address the challenges and achieve the World Health Organization Millennium
      Development Goals (MDGs) within a context of limited resources. CASE DESCRIPTION:
      The health system was reformed to create a platform for integration and
      institutionalization of the HEP with appropriate human capacity, infrastructure,
      and management structures. Human resources were developed through training of
      female health workers recruited from their prospective villages, designed to
      limit the high staff turnover and address gender, social and cultural factors in
      order to provide services acceptable to each community. The service delivery
      modalities include household, community and health facility care. Thus, the most
      basic health post infrastructure, designed to rapidly and cost-effectively scale
      up HEP, was built in each village. In line with the country's decentralized
      management system, the HEP service delivery is under the jurisdiction of the
      district authorities. DISCUSSION AND EVALUATION: The nationwide implementation of
      HEP progressed in line with its target goals. In all, 40 training institutions
      were established, and over 30,000 Health Extension Workers have been trained and
      deployed to approximately 15,000 villages. The potential health service coverage
      reached 92.1% in 2011, up from 64% in 2004. While most health indicators have
      improved, performance in skilled delivery and postnatal care has not been
      satisfactory. While HEP is considered the most important institutional framework
      for achieving the health MDGs in Ethiopia, quality of service, utilization rate,
      access and referral linkage to emergency obstetric care, management, and
      evaluation of the program are the key challenges that need immediate attention.
      CONCLUSIONS: This article describes the strategies, human resource developments,
      service delivery modalities, progress in service coverage, and the challenges in
      the implementation of the HEP. The Ethiopian approach of revitalization of
      primary care through innovative, locally appropriate and acceptable strategies
      will provide important lessons to other poorly resourced countries. It is hoped
      that the approaches and strategies described in this paper will aid in that
      process.

PMID- 23961921
TI  - Ecological and genetic factors influencing the transition between host-use
      strategies in sympatric Heliconius butterflies.
AB  - Shifts in host-plant use by phytophagous insects have played a central role in
      their diversification. Evolving host-use strategies will reflect a trade-off
      between selection pressures. The ecological niche of herbivorous insects is
      partitioned along several dimensions, and if populations remain in contact,
      recombination will break down associations between relevant loci. As such,
      genetic architecture can profoundly affect the coordinated divergence of traits
      and subsequently the ability to exploit novel habitats. The closely related
      species Heliconius cydno and H. melpomene differ in mimetic colour pattern,
      habitat and host-plant use. We investigate the selection pressures and genetic
      basis underlying host-use differences in these two species. Host-plant surveys
      reveal that H. melpomene specializes on a single species of Passiflora. This is
      also true for the majority of other Heliconius species in secondary growth forest
      at our study site, as expected under a model of interspecific competition. In
      contrast, H. cydno, which uses closed-forest habitats where both Heliconius and
      Passiflora are less common, appears not to be restricted by competition and uses
      a broad selection of the available Passiflora. However, other selection pressures
      are likely involved, and field experiments reveal that early larval survival of
      both butterfly species is highest on Passiflora menispermifolia, but most
      markedly so for H. melpomene, the specialist on that host. Finally, we
      demonstrate an association between host-plant acceptance and colour pattern
      amongst interspecific hybrids, suggesting that major loci underlying these
      important ecological traits are physically linked in the genome. Together, our
      results reveal ecological and genetic associations between shifts in habitat,
      host use and mimetic colour pattern that have likely facilitated both speciation
      and coexistence. 

PMID- 23961922
TI  - Endocrine phenotype, reproductive success and survival in the great tit, Parus
      major.
AB  - A central goal in evolutionary ecology is to characterize and identify selection
      patterns on the optimal phenotype in different environments. Physiological
      traits, such as hormonal responses, provide important mechanisms by which
      individuals can adapt to fluctuating environmental conditions. It is therefore
      expected that selection shapes hormonal traits, but the strength and the
      direction of selection on plastic hormonal signals are still under investigation.
      Here, we determined whether, and in which way, selection is acting on the
      hormones corticosterone and prolactin by characterizing endocrine phenotypes and
      their relationship with fitness in free-living great tits, Parus major. We
      quantified variation in circulating concentrations of baseline and stress-induced
      corticosterone and in prolactin during the prebreeding (March) and the breeding
      season (May) for two consecutive years, and correlated these with reproductive
      success (yearly fledgling number) and overwinter survival in female and male
      individuals. In both years, individuals with high baseline corticosterone
      concentrations in March had the highest yearly fledgling numbers; while in May,
      individuals with low baseline corticosterone had the highest yearly reproductive
      success. Likewise, individuals that displayed strong seasonal plasticity in
      baseline corticosterone concentrations (high in March and low in May) had the
      highest reproductive success in each year. Prolactin concentrations were not
      related to reproductive success, but were positively correlated to the proximity
      to lay. Between-year plasticity in stress-induced corticosterone concentrations
      of males was related to yearly variation in food abundance, but not to overall
      reproductive success. These findings suggest that seasonally alternating
      directional selection is operating on baseline corticosterone concentrations in
      both sexes. The observed between-year consistency in selection patterns indicates
      that a one-time hormone sample in a given season can allow the prediction of
      individual fitness. 

PMID- 23961923
TI  - The impact of reproductive investment and early-life environmental conditions on
      senescence: support for the disposable soma hypothesis.
AB  - Several hypotheses have been put forward to explain the evolution of senescence.
      One of the leading hypotheses, the disposable soma hypothesis, predicts a trade
      off, whereby early-life investment in reproduction leads to late-life declines in
      survival (survival senescence). Testing this hypothesis in natural populations is
      challenging, but important for understanding the evolution of senescence. We used
      the long-term data set from a contained, predator-free population of individually
      marked Seychelles warblers (Acrocephalus sechellensis) to investigate how age
      related declines in survival are affected by early-life investment in
      reproduction and early-life environmental conditions. The disposable soma
      hypothesis predicts that higher investment in reproduction, or experiencing harsh
      conditions during early life, will lead to an earlier onset, and an increased
      rate, of senescence. We found that both sexes showed similar age-related declines
      in late-life survival consistent with senescence. Individuals that started
      breeding at a later age showed a delay in survival senescence, but this later
      onset of breeding did not result in a less rapid decline in late-life survival.
      Although survival senescence was not directly related to early-life environmental
      conditions, age of first breeding increased with natal food availability.
      Therefore, early-life food availability may affect senescence by influencing age
      of first breeding. The disposable soma hypothesis of senescence is supported by
      delayed senescence in individuals that started breeding at a later age and
      therefore invested less in reproduction. 

PMID- 23961925
TI  - Association of chiropractic colleges educational conference and research agenda
      conference 2013.

PMID- 23961927
TI  - On processing the information from knowledge of results.
AB  - A basic assumption of cognitive theories of learning is that subjects actively
      operate upon the knowledge of results (KR) they receive. Tests of this assumption
      in motor skills contexts, however, have yielded conflicting data. The relevant
      studies are critically examined. A number of methodological problems are
      discussed which may have contributed to the equivocality of the extant data on
      the processing of KR during the post-KR period. 

PMID- 23961926
TI  - Effects of baclofen on mechanical noxious and innocuous transmission in the
      spinal dorsal horn of the adult rat: in vivo patch-clamp analysis.
AB  - The effects of a GABAB agonist, baclofen, on mechanical noxious and innocuous
      synaptic transmission in the substantia gelatinosa (SG) were investigated in
      adult rats with the in vivo patch-clamp technique. Under current-clamp
      conditions, perfusion with baclofen (10 MUm) on the surface of the spinal cord
      caused hyperpolarisation of SG neurons and a decrease in the number of action
      potentials elicited by pinch and touch stimuli applied to the receptive field of
      the ipsilateral hindlimb. The suppression of action potentials was preserved
      under blockade of postsynaptic G-proteins, although baclofen-induced
      hyperpolarisation was completely blocked. These findings suggest presynaptic
      effects of baclofen on the induced action potentials. Under voltage-clamp
      conditions, application of baclofen reduced the frequency, but not the amplitude,
      of miniature excitatory postsynaptic currents (mEPSCs), whereas the GABAB
      receptor antagonist CGP55845 increased the frequency of mEPSCs without affecting
      the amplitude. Furthermore, application of a GABA uptake inhibitor, nipecotic
      acid, decreased the frequency of mEPSCs; this effect was blocked by CGP55845, but
      not by the GABAA antagonist bicuculline. Both the frequency and the amplitude of
      the pinch-evoked barrage of excitatory postsynaptic currents (EPSCs) were
      suppressed by baclofen in a dose-dependent manner. The frequency and amplitude of
      touch-evoked EPSCs was also suppressed by baclofen, but the suppression was
      significantly smaller than that of pinch-evoked EPSCs. We conclude that
      mechanical noxious transmission is presynaptically blocked through GABAB
      receptors in the SG, and is more effectively suppressed than innocuous
      transmission, which may account for a part of the mechanism of the efficient
      analgesic effects of baclofen. 

PMID- 23961928
TI  - On the genesis of human handedness.
AB  - The evidence for genetic, learning, and pathological antecedents of human
      handedness was reviewed. There is direct evidence for a genetic component in
      handedness. In addition, there is a great deal of incidental evidence that is
      consistent with a genetic hypothesis. There is also some evidence for
      pathological left-handedness in a small minority of people. Little evidence
      supports the hypothesis that handedness is learned. 

PMID- 23961929
TI  - Motivational effects of outcome feedback on motor performance.
AB  - This study examined the effects of success and failure feedback on subsequent
      motor performance. Based upon the general motivation (or level-of-aspiration)
      hypothesis, initial success should lead to better subsequent performance than
      does initial failure, while the reverse prediction was derived from the cognitive
      dissonance theory. To test these rival hypotheses, two experiments were conducted
      on undergraduate male students (n =120) performing a motor maze task. Initial
      failure improved subjects' subsequent performance, thus supporting the dissonance
      theory. However, this effect was observed only under low-ego-involving
      conditions, thereby suggesting that the effects of dissonance and ego involvement
      are interdependent. The findings were discussed in terms of motivational and
      informational/attributional effects of outcome feedback on motor performance. 

PMID- 23961924
TI  - All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS)
      compared with the general population: 1997-2010.
AB  - BACKGROUND: Combination antiretroviral therapy (cART) has produced significant
      changes in mortality of HIV-infected persons. Our objective was to estimate
      mortality rates, standardized mortality ratios and excess mortality rates of
      cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the
      general population. METHODS: We analysed data of CoRIS-MD and CoRIS cohorts from
      1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized
      mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100
      person-years (py) of follow-up, comparing all-cause mortality with that of the
      general population of similar age and gender. RESULTS: Between 1997 and 2010,
      8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761
      (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was
      1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess
      mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in
      patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD
      cohort (1997-2003). CONCLUSION: Mortality among HIV-positive persons remains
      higher than that of the general population of similar age and sex, with
      significant differences depending on the history of AIDS or HCV coinfection.

PMID- 23961930
TI  - The effects on skill acquisition of an interpolated motor short-term memory task
      during the kr-delay interval.
AB  - The effects of an interpolated motor short-term memory task during the KR-delay
      interval on skill acquisition was investigated. On each trial subjects estimated
      two positions on a linear-positioning apparatus. One group of subjects was
      presented two biasing movements, which they immediately recalled, during the KR
      delay interval. The interpolated motor short-term memory task interfered with
      skill acquisition and retention. 

PMID- 23961931
TI  - Measuring change in motor memory.
AB  - While research into the processes underlying motor memory has burgeoned in the
      past decade, issues as to what dependent measure(s) to use (i.e., AE, E, CE, or
      VE) have not been adequately resolved. Does one use a single (composite) meausre
      (i.e., AE or E) or its components (i.e., CE and VE)? If one decides to use a
      single measure, either AE or E, which is more appropriate? A cursory examination
      of the reported literature dealing with motor memory reveals a decided lack of
      cross-experimental consistency in the use of dependent measures that can only
      serve to impede a clear understanding of memory processes. It is argued here that
      in order to improve cross-experimental comparison and to facilitate a clearer
      understanding of what each of these measures mean in terms of memory processes
      all three (i.e., AE or E, CE, and VE) should be reported. 

PMID- 23961932
TI  - Smallest-space analysis of visual pursuit in children.
AB  - A three-dimensional model of visual pursuit was tested using data of Roach and
      Kephart (1966) for 200 elementary school children and the recently developed
      nonmetric multidimensional scaling procedure of smallest-space analysis. The
      latter technique was briefly reviewed and contrasted with traditional factor
      analysis. Two dimensions were clearly identified by smallest-space analysis as
      Monocular-Binocular Tracking and Laterality; a third dimension, Direction of
      Pursuit, was less well identified. The usefulness of smallest-space analysis in
      identifying the dimensionality of such multivariate data gathered under
      naturalistic conditions, where metrical assumptions may not always be met, was
      argued. That the dimensionality may be influenced by experimental factors, as
      well as perhaps age, sex, organicity, etc., was mentioned, and suggestions for
      further research were made. Requests for reprints should be sent to Frank H.
      Farley, 1025 W. Johnson Street, University of Wisconsin, Madison, Wisconsin
      53706. 

PMID- 23961933
TI  - The effects of initial habit strength differences upon performance in a coaction
      situation.
AB  - The present investigation examined the effects of initial habit strength
      differences upon performance in a coaction situation. During a training session,
      a habit-strength hierarchy was developed in each of three groups through the
      establishment of a differential response expectancy for each of four alternative
      responses. In a subsequent test session, both performance and consistency of
      performance were affected by the pretraining on the correct habit. However, there
      was no statistical support for the hypothesis that coaction would interact with
      the habit-strength condition resulting in an improvement in the coaction/habit
      correct group and a decrement in the coaction/habit-incorrect group. Similarly,
      no differences were found between the coaction and alone conditions. 

PMID- 23961934
TI  - Distribution of practice as a factor affecting learning and/or performance.
AB  - Earlier studies considering distribution of practice as a factor affecting
      learning and/or performance have employed a transfer design and consequently have
      failed to provide the means for refuting the contention that postrest performance
      was the manifestation of extended practice, a temporary performance variation, or
      some form of the "Hawthorne effect" rather than the result of the independent
      variable. The present experiment provided adequate control, and results indicated
      that distribution of practice was a factor affecting performance rather than
      learning. 

PMID- 23961935
TI  - Feedback in response recognition and production.
AB  - The role of feedback in the development of recognition memory was examined by
      testing pairs of subjects; one subject performed the movement while the other
      listened to the movement in an adjacent room. Both groups of subjects developed
      recognition memory during training with KR, and recognition performance was
      virtually identical for both groups. In addition, previous experience with the
      sensory consequences of the movement led to improved response production during
      initial trials. A possible mechanism to account for this finding is proposed.
      Appreciation is extended to Richard A. Schmidt and Anne Marie Bird for helpful
      comments in earlier drafts of this paper. 

PMID- 23961936
TI  - A note concerning the effect of a kinesthetic memory load on the retention of
      movement end-location.
AB  - Remembering the distance or end-location of an interpolated movement interfered
      equally with the retention of criterion movement end-location. Interpolated
      distances were recalled less well than interpolated locations. These results were
      interpreted as evidence of capacity interference rather than structural
      interference with a visual/kinesthetic integrated store. 

PMID- 23961937
TI  - Surgical site infections in skin surgery: a single center experience.
AB  - The main interests covered in this article are the determination of risk factors
      and incidence of surgical site infections in dermatosurgery and suggestions for
      rational use of antibiotic prophylaxis. A total of 3284 consecutive
      dermatosurgical interventions in 1088 patients were performed in our
      dermatosurgery department. Data regarding patient characteristics and
      perioperative course were prospectively collected and retrospective analysis of
      this data was performed. Association of perioperative parameters and
      postoperative surgical site infections was assessed by chi(2) -test. Rate of
      postoperative infections in our study was low (1.9%). Purulent surgical sites
      showed the highest incidence of severe postoperative infections (4.7%; P <
      0.001). The lowest incidence of mild infections was seen in preoperatively clean
      surgical sites (0.8%; P < 0.001). All patients with severe infections and 68%
      patients with mild infections were older than 70 years. The head and neck and
      acral regions were the groups mostly affected by mild postoperative conditions
      (2.4% and 1.7%, respectively; P = 0.006). The frequency of mild and severe
      infections in procedures performed by experienced surgeons was lower than in
      procedures performed by less experienced surgeons (0.6% vs 3.1% in mild
      infections, 0.1 vs 0.8 in severe infections; P < 0.001). The main risk factors
      for postoperative infections were wounds in the head and neck region, lips and
      oral mucosa or acral regions, older age of patients, worse preoperative state of
      surgical sites and less experienced surgeons. In the majority of cases where risk
      factors were missing there was no need of antibiotic prophylaxis.

PMID- 23961938
TI  - Automatic nuclear bud detection using ellipse fitting, moving sticks or top-hat
      transformation.
AB  - Micronucleus assays are extensively used by biologists to assess genotoxicity and
      to monitor human exposure to genotoxic materials. As recent studies suggested
      that nuclear buds can be a new source of micronuclei formed in interphase, the
      quantification of nuclear buds, which are micronucleus like objects that are
      attached to the nuclei in interphase, in normal and control group is needed.
      Three automatic nuclear bud detection algorithms fit for different situations are
      proposed in this paper. One is based on ellipse fitting, one is based on a stick
      model and the other is based on the top-hat transform. Comparison of the three
      methods is also given in this paper. Experimental results showed that the
      proposed algorithms are all effective and efficient for nuclear bud detection. 

PMID- 23961939
TI  - Salicylic acid-dependent and -independent impact of an RNA-binding protein on
      plant immunity.
AB  - Plants overexpressing the RNA-binding protein AtGRP7 (AtGRP7-ox plants)
      constitutively express the PR-1 (PATHOGENESIS-RELATED-1), PR-2 and PR-5
      transcripts associated with salicylic acid (SA)-mediated immunity and show
      enhanced resistance against Pseudomonas syringae pv. tomato (Pto) DC3000. Here,
      we investigated whether the function of AtGRP7 in plant immunity depends on SA.
      Endogenous SA was elevated fivefold in AtGRP7-ox plants. The elevated PR-1, PR-2
      and PR-5 levels were eliminated upon expression of the salicylate hydroxylase
      nahG in AtGRP7-ox plants and elevated PR-1 levels were suppressed by sid
      (salicylic acid deficient) 2-1 that is impaired in SA biosynthesis. RNA
      immunoprecipitation showed that AtGRP7 does not bind the PR-1 transcript in vivo,
      whereas it binds PDF1.2. Constitutive or inducible AtGRP7 overexpression
      increases PR-1 promoter activity, indicating that AtGRP7 affects PR-1
      transcription. In line with this, the effect of AtGRP7 on PR-1 is suppressed by
      npr (non-expressor of PR genes) 1. Whereas AtGRP7-ox plants restricted growth of
      Pto DC3000 compared with wild type (wt), sid2-1 AtGRP7-ox plants allowed more
      growth than AtGRP7-ox plants. Furthermore, we show an enhanced hypersensitive
      response triggered by avirulent Pto DC3000 (AvrRpt2) in AtGRP7-ox compared with
      wt. In sid2-1 AtGRP7-ox, an intermediate phenotype was observed. Thus, AtGRP7 has
      both SA-dependent and SA-independent effects on plant immunity. 

PMID- 23961940
TI  - Effectiveness of t'ai chi and qigong on chronic obstructive pulmonary disease: a
      systematic review and meta-analysis.
AB  - PURPOSE: The purpose of this study is to determine the effects of Chinese
      traditional exercise such as t'ai chi and qigong (TCQ) on patients with chronic
      obstructive pulmonary disease (COPD). METHODS: All prospective, randomized,
      controlled clinical trials, published in English or Chinese and involving the use
      of TCQ by patients with COPD, were searched in 10 electronic databases from their
      respective inceptions to July 2012. The methodological quality of all studies was
      assessed using the Jadad score. The selection of studies, data extraction, and
      quality assessment were performed independently by two raters. RESULTS: In the
      results, 10 trials met the inclusion criteria and were reviewed. The meta
      analysis demonstrated that compared with no exercise, TCQ had significant effects
      on 6-minute walk distance, forced expiratory volume in 1 second (FEV1), predicted
      FEV1 percentage, and St. George's Respiratory Questionnaire score. There were no
      significant differences in all outcomes between TCQ and other exercise training
      except 6-minute walk distance. CONCLUSIONS: In conclusion, TCQ might be
      beneficial with respect to physical performance, lung function, remission of
      dyspnea, and quality of life in patients with COPD; however, caution is needed to
      draw a firm conclusion because of the low methodological quality of the included
      trials.

PMID- 23961942
TI  - Impact of alternative solid state forms and specific surface area of high-dose,
      hydrophilic active pharmaceutical ingredients on tabletability.
AB  - In order to investigate the effect of using different solid state forms and
      specific surface area (TBET) of active pharmaceutical ingredients on
      tabletability and dissolution performance, the mono- and dihydrated crystalline
      forms of chlorothiazide sodium and chlorothiazide potassium (CTZK) salts were
      compared to alternative anhydrous and amorphous forms, as well as to amorphous
      microparticles of chlorothiazide sodium and potassium which were produced by
      spray drying and had a large specific surface area. The tablet hardness and
      tensile strength, porosity, and specific surface area of single-component, convex
      tablets prepared at different compression pressures were characterized. Results
      confirmed the complexity of the compressibility mechanisms. In general it may be
      concluded that factors such as solid-state form (crystalline vs amorphous), type
      of hydration (presence of interstitial molecules of water, dehydrates), or
      specific surface area of the material have a direct impact on the tabletability
      of the powder. It was observed that, for powders of the same solid state form,
      those with a larger specific surface area compacted well, and better than powders
      of a lower surface area, even at relatively low compression pressures. Compacts
      prepared at lower compression pressures from high surface area porous
      microparticles presented the shortest times to dissolve, when compared with
      compacts made of equivalent materials, which had to be compressed at higher
      compression pressures in order to obtain satisfactory compacts. Therefore,
      materials composed of nanoparticulate microparticles (NPMPs) may be considered as
      suitable for direct compaction and possibly for inclusion in tablet formulations
      as bulking agents, APIs, carriers, or binders due to their good compactibility
      performance. 

PMID- 23961943
TI  - Spatial selective attention affects early extrastriate but not striate components
      of the visual evoked potential.
AB  - Abstract The effects of spatial selective attention on sensory processing in
      visual cortical areas were investigated by means of visual evoked potential (VEP)
      recordings and source localization techniques. Patterned stimuli were rapidly
      presented in random order to the left and right visual fields while subjects
      maintained central fixation and attended to one visual field at a time. Attended
      stimuli evoked enhanced P1 (100-130 msec) and N1 (120-200 msec) components of the
      VEP, whereas no effects of attention were observed on the C1 (50-100 msec) or P2
      (200-240 msec) components. Spatiotemporal dipole modeling of the early VEP
      sources was carried out in relation to MRI-defined cortical anatomy. The dipolar
      generator of the C1 component was found to lie in calcarine cortex, the human
      homologue of area V1, whereas the attention-sensitive P1 generator was localized
      to ventral-lateral occipital cortex, within extrastriate area 19. These results
      support the hypothesis that spatial attention does not affect the initial
      activity evoked in area V1 but rather produces an enhancement within extrastriate
      visual areas of sensory signals arising from stimuli at attended locations. 

PMID- 23961941
TI  - Use of electron paramagnetic resonance to solve biochemical problems.
AB  - Electron paramagnetic resonance (EPR) spectroscopy is a very powerful biophysical
      tool that can provide valuable structural and dynamic information about a wide
      variety of biological systems. The intent of this review is to provide a general
      overview for biochemists and biological researchers of the most commonly used EPR
      methods and how these techniques can be used to answer important biological
      questions. The topics discussed could easily fill one or more textbooks; thus, we
      present a brief background on several important biological EPR techniques and an
      overview of several interesting studies that have successfully used EPR to solve
      pertinent biological problems. The review consists of the following sections: an
      introduction to EPR techniques, spin-labeling methods, and studies of naturally
      occurring organic radicals and EPR active transition metal systems that are
      presented as a series of case studies in which EPR spectroscopy has been used to
      greatly further our understanding of several important biological systems. 

PMID- 23961944
TI  - Interactions between Transient and Long-Term Auditory Memory as Reflected by the
      Mismatch Negativity.
AB  - Abstract The mismatch negativity (MMN) event-related potential (ERP) component is
      elicited by any discriminable change in series of repetitive auditory stimuli.
      MMN is generated by a process registering the deviation of the incoming stimulus
      from the trace of the previous repetitive stimulus. Using MMN as a probe into
      auditory sensory memory, the present study addressed the question of whether the
      sensory memory representation is formed strictly on the basis of an automatic
      feature analysis of incoming sensory stimuli or information from long-term memory
      is also incorporated. Trains of 6 tone bursts (standards with up to 1 deviant per
      train) separated by 9.5-sec intertrain intervals were presented to subjects
      performing a visual tracking task and disregarding the auditory stimuli. Trains
      were grouped into stimulus blocks of 20 trains with a 2-min rest period between
      blocks. In the Constant-Standard Condition, both standard and deviant stimuli
      remained fixed across the session, encouraging the formation of a long-term
      memory representation. To eliminate the carryover of sensory storage from one
      train to the next, the first 3.6 sec of the intertrain interval was filled with 6
      tones of random frequencies. In the Roving-Standard Condition, the standard
      changed from train to train and the intervening tones were omitted. It was found
      that MMN was elicited by deviants presented in Position 2 of the trains in the
      Constant-Standard Condition revealing that a single reminder of the constant
      standard reactivated the standard-stimulus representation. The MMN amplitude
      increased across trials within each stimulus block in the Constant- but not in
      the Roving-Standard Condition, demonstrating long-term learning in that condition
      (i.e., the standard-stimulus trace indexed by the MMN amplitude benefitted from
      the presentations of the constant standard in the previous trains). The present
      results suggest that the transient auditory sensory memory representation
      underlying the MMN is facilitated by a longer-term representation of the
      corresponding stimulus. 

PMID- 23961945
TI  - Long-term retention deficits in two cases of disproportionate retrograde amnesia.
AB  - Abstract The status of very long-term retention, together with detailed brain
      imaging correlates, is presented in two patients with disproportionately dense
      retrograde amnesia. The first patient suffered a severe closed head injury and
      was left with dense autobiographical amnesia for events that she had experienced
      prior to her injury. She showed relatively mild, patchy memory impairment on
      standard anterograde memory tests. Postinjury autobiographical memory was
      relatively spared. However, postinjury long-term knowledge acquisition was
      significantly impaired. The second patient also suffered a severe head injury and
      was left with marked retrograde amnesia for events that she had experienced prior
      to her injury. She also showed relatively mild, patchy impairment on standard
      anterograde memory tests. Using specially designed tests, this patient showed
      normal immediate learning and delayed recall using a range of materials, but
      displayed significantly faster rate of forgetting over a period of 6 weeks than
      control subjects who were matched on initial delayed levels of retention. In both
      cases, there was major pathology in the region of the left temporal lobe, with
      lateral structures being more affected than medial structures. Our findings
      provide further evidence relating to the independence of certain anterograde and
      retrograde memory mechanisms, and support recent observations (De Renzi &
      Lucchelli, 1993) that link some instances of retrograde amnesia to impairment in
      very long-term retention. The possibility is raised that some forms of retrograde
      amnesia, such as the present cases, represent a type of "disconnection syndrome,"
      whereby visual-semantic and other associations are disconnected from verbal
      representations of such associations. Lesions to intrahemispheric fasciculi or
      similar association fibers, in combination with lesions to critical anterior or
      posterior cerebral structures, may play an important role in such a
      disconnection. 

PMID- 23961946
TI  - The effects of adapting to complex motions: position invariance and tuning to
      spiral motions.
AB  - Abstract Recent neurophysiological evidence (e.g., Graziano, Andersen, & Snowden,
      1994) suggested that some cells in the medial superior temporal area (MST) of the
      Old World monkey are sensitive to complex motions such as those brought about by
      a surface moving in depth or rotating. Two important findings were that these
      cells show position invariance (i.e., their preferred stimulus does not change
      across the receptive field), and that some cells were selective for "spiralling"
      stimuli rather than pure rotations or pure expansion/contractions. This paper
      attempts to provide evidence for similar processes in the human visual system by
      employing the technique of selective adaptation. We have simulated surfaces
      undergoing a motion in depth (div) or a rotation (curl), but have removed any
      cues that are not related to global motion. After adapting to a large pattern
      undergoing, say, an expansion, an aftereffect that contained an element of
      contraction could be elicited by placing small test patterns anywhere in the
      adapted area. This suggests that the global structure of the motion field must
      have been encoded as well as the local motion. Likewise thresholds for detecting
      motions similar to the adapting motion were elevated across the adapted area,
      while thresholds for other motions were not. Hence the effects of adaptation are
      both selective and show a degree of position invariance. Adaptation to pure div
      or pure curl stimuli was compared with adaptation to spiralling stimuli.
      Threshold elevation was always selective for the adapting motion and the shape
      and broadness of tuning did not vary. In simulations we could not reproduce our
      results using a model that had only div and curl detectors, but we could
      reproduce them if we allowed for detectors tuned for a broad range of spiral
      pitches. Our results suggest that humans encode the complex motion of surfaces by
      detectors tuned to many different types of motion and that the detectors are
      invariant across space in their properties. 

PMID- 23961947
TI  - Dissociations in the processing of "what" and "where" information in working
      memory: an event-related potential analysis.
AB  - Abstract Based on recent research that suggests that the processing of spatial
      and object information in the primate brain involves functionally and
      anatomically different systems, we examined whether the encoding and retention of
      object and spatial information in working memory are associated with different
      ERP components. In a study-test procedure subjects were asked to either remember
      simple geometric objects presented in a 4 by 4 spatial matrix irrespective of
      their position (object memory task) or to remember spatial positions of the
      objects irrespective of their forms (spatial memory task). The EEG was recorded
      from 13 electrodes during the study phase and the test phase. Recognition
      performance (reaction time and accuracy) was not different for the two memory
      tasks. PCA analyses suggest that the same four ERP components are evoked in the
      study phase by both tasks, which could be identified as N100, P200, P300, and
      slow wave. ERPs started to differ as a function of memory task 225 msec after
      stimulus onset at the posterior recording sites: An occipital maximal P200
      component, lateralized to the right posterior temporal recording site, was
      observed for the object memory but not for the spatial memory task. Between-tasks
      differences were also obtained for P300 scalp distribution. Moreover, ERPs evoked
      by objects that were remembered later were more positive than ERPs to objects
      that were not remembered, starting at 400 msec postsimulus. The PCA analysis
      suggest that P300 and a slow wave following P300 at the frontal recordings
      contribute to these differences. A similar differential effect was not found
      between positions remembered or not remembered later. Post hoc analyses revealed
      that the absence of such effects in the spatial memory task could be due to less
      elaborated mnemonic strategies used in the spatial task compared to the object
      memory task. In the face of two additional behavioral experiments showing that
      subjects exclusively encode object features in the object memory task and spatial
      stimulus features in the spatial memory task, the present data provide evidence
      that encoding and rehearsal of object and spatial information in working memory
      are subserved by functionally and anatomically different subsystems. 

PMID- 23961948
TI  - Interview with robert g. Shulman.
AB  - Robert G. Shulman is the Sterling Professor of Molecular Biophysics and
      Biochemistry at Yale University. He received his B.A. and Ph.D. degrees at
      Columbia in physical chemistry, with an intervening period as Lt(jg) USNR. Soon
      after graduate studies with C. H. Townes in microwave spectroscopy, he went to
      Bell Telephone Laboratories, where he started Nuclear Magnetic Resonance research
      on antiferromagnetics; superconductors; semiconductors; and, eventually,
      biomolecules. A year working with F. H. C. Crick and S. Brenner on phage genetics
      solidified his interest in biophysics. He started and led biophysics research at
      Bell Labs, where he studied a variety of biomolecules by NMR. This led him to in
      vivo NMR, at first in microorganisms; then animals; and, finally, humans. Since
      1979 he has been at Yale University, where he has been following metabolism in
      vivo by magnetic resonance in brain and muscle measuring changes during
      activation. He is a member of the National Academy of Sciences and Institute of
      Medicine. 

PMID- 23961949
TI  - Errata.

PMID- 23961950
TI  - Surveillance transbronchial biopsies in infant lung and heart-lung transplant
      recipients.
AB  - There are limited published data on surveillance TBB for the identification of
      allograft rejection in infants after lung or heart-lung transplantation. We
      performed a retrospective review of children under one yr of age who underwent
      lung or heart-lung transplant at our institution. Since 2005, four infants were
      transplanted (three heart-lung and one lung). The mean age (+/-s.d.) at the time
      of transplant was 5.5 +/- 2.4 (range 3-8) months. A total of 16 surveillance TBB
      procedures were completed in both inpatient and outpatient settings, with a range
      of 3-7 performed per patient. A minimum of five acceptable tissue pieces with
      expanded alveoli were obtained in 81% (13/16) of TBB procedures and a minimum of
      three pieces in 88% (14/16). There was no evidence of acute allograft rejection
      in 88% (14/16) of TBB procedures. One TBB procedure yielded two tissue specimens
      demonstrating A2 acute allograft rejection. One TBB procedure failed to yield
      tissue with sufficient alveoli. Additionally, B-grade assessment identified B0 in
      50% (8/16), B1R in 12% (2/16), and BX (ungradeable or insufficient sample) in 38%
      (6/16) of biopsy procedures, respectively. In conclusion, TBB may be safely
      performed as an inpatient and outpatient procedure in infant lung and heart-lung
      transplant recipients and may provide adequate tissue for detecting acute
      allograft rejection and small airway inflammation. 

PMID- 23961951
TI  - Laparoendoscopic single-site surgery with a single channel versus conventional
      laparoscopic varicocele ligation: a prospective randomized study.
AB  - PURPOSE: The objective of this study was to evaluate the safety and feasibility
      of single channel laparoscopy in the treatment of patients with varicocele.
      PATIENTS AND METHODS: Ninety patients with clinically palpable varicoceles were
      randomly assigned to receive laparoendoscopic single-site with a single channel
      varicocele ligation (LESS[sc]-VL) (n=45) or conventional transperitoneal
      laparoscopic varicocele ligation (CTL-VL) (n=45). Patient characteristics,
      perioperative details, total procedural cost, time to return to work, visual
      analogue scale (VAS) pain score, semen parameters, and cosmetic results were
      recorded. RESULTS: There were no differences in operative time (P=0.102),
      postoperative hospitalization time (P=0.130), total cost (P=0.112), or
      postoperative complications (P>0.05) between the two groups. Time to return to
      normal activities was shorter in the LESS(sc)-VL group than that in the CTL-VL
      group (P=0.018). The mean of all semen parameters were improved statistically 3
      months after ligation (P<0.001). The VAS incision pain score was significantly
      lower 6 and 24 hours after surgery in patients who underwent LESS(sc)-VL(P<0.05).
      Patients who underwent LESS(sc)-VL had a better cosmetic result, reflected by
      both the verbal response scale and the numeric scale (P=0.008 and P=0.005,
      respectively). CONCLUSIONS: LESS(sc)-VL is a safe and effective minimally
      invasive surgical alternative for varicocelectomy. Compared with CTL-VL, LESS(sc)
      VL may decrease postoperative pain and hide the surgical incision better within
      the umbilicus.

PMID- 23961952
TI  - Multimorbidity and equity in health.

PMID- 23961953
TI  - Screening and evaluation of small organic molecules as ClpB inhibitors and
      potential antimicrobials.
AB  - Inhibition of ClpB, the bacterial representative of the heat-shock protein 100
      family that is associated with virulence of several pathogens, could be an
      effective strategy to develop new antimicrobial agents. Using a high-throughput
      screening method, we have identified several compounds that bind to different
      conformations of ClpB and analyzed their effect on the ATPase and chaperone
      activities of the protein. Two of them inhibit these functional properties as
      well as the growth of Gram negative bacteria (E. coli), displaying antimicrobial
      activity under thermal or oxidative stress conditions. This activity is abolished
      upon deletion of ClpB, indicating that the action of these compounds is related
      to the stress cellular response in which ClpB is involved. Moreover, their
      moderate toxicity in human cell lines suggests that they might provide promising
      leads against bacterial growth. 

PMID- 23961954
TI  - The use of novel TherakosTM Cellex(r) for extracorporeal photopheresis in
      treatment of graft-versus-host disease in paediatric patients.
AB  - Extracorporeal photopheresis (ECP) is an established second line treatment option
      for graft-versus-host disease (GVHD) post-haematopoietic progenitor cell
      transplant. At our centre, the TherakosTM Cellex((r)) has replaced the TherakosTM
      UVAR-XTSTM machine for ECP since 2009. We reviewed the records of 385 procedures
      using the TherakosTM Cellex((r)) for safety and tolerability. Nine patients
      underwent ECP for GVHD. The median age was 13.5 years (range 3.7-24) and weight
      was 49.2 kg (range 18.5-86.3). The mean duration per procedure was 106 min (range
      60-205). Fifteen (3.9%) procedures were cancelled and 10 (2.6%) were delayed,
      with central venous line (CVL) issues being the most frequent problem. With the
      use of prophylactic tissue plasminogen activator, fewer CVL-related occlusions
      were observed (4.7% vs. 2.3%). There was one episode of a CVL-associated
      thrombosis and one episode of delayed bleeding. There were four episodes of viral
      reactivation, four CVL-associated infections (1142 catheter days) and one episode
      of systemic inflammatory response syndrome. No patient experienced symptomatic
      hypotension. This is the first report outlining the safety and tolerability of
      the TherakosTM Cellex((r)) device for ECP in children and young adults. 

PMID- 23961955
TI  - 'Maternity migration' and the increased sex ratio at birth in Hong Kong SAR.
AB  - The sex ratio at birth (SRB) in Hong Kong SAR (Special Administrative Region) has
      recently increased dramatically. Using a data set (N = 850,331) of all recorded
      births in Hong Kong between 1995 and 2009, we calculated SRBs by parity and
      immigrant status. The findings indicate a strong son preference among Mainland
      Chinese who have travelled to Hong Kong to give birth, especially at parity two
      or above. Logistic regression models show that this tendency is significantly
      greater among more affluent couples and remains strong even among Mainland
      Chinese women resident in Hong Kong for any length of time. The SRB of Hong Kong
      born couples, though elevated at higher parities, is less skewed. Hong Kong has
      been serving as an outlet for 'elite' Mainland couples to circumvent family
      planning restrictions. The analysis also suggests the advantages of a wider set
      of immigrant variables over a binary construct. 

PMID- 23961956
TI  - Promoting universal financial protection: evidence from the Rashtriya Swasthya
      Bima Yojana (RSBY) in Gujarat, India.
AB  - BACKGROUND: India's health expenditure is met mostly by households through out-of
      pocket (OOP) payments at the time of illness. To protect poor families, the
      Indian government launched a national health insurance scheme (RSBY). Those below
      the national poverty line (BPL) are eligible to join the RSBY. The premium is
      heavily subsidised by the government. The enrolled members receive a card and can
      avail of free hospitalisation care up to a maximum of US$ 600 per family per
      year. The hospitals are reimbursed by the insurance companies. The objective of
      our study was to analyse the extent to which RSBY contributes to universal health
      coverage by protecting families from making OOP payments. METHODS: A two-stage
      stratified sampling technique was used to identify eligible BPL families in Patan
      district of Gujarat, India. Initially, all 517 villages were listed and 78 were
      selected randomly. From each of these villages, 40 BPL households were randomly
      selected and a structured questionnaire was administered. Interviews and
      discussions were also conducted among key stakeholders. RESULTS: Our sample
      contained 2,920 households who had enrolled in the RSBY; most were from the
      poorer sections of society. The average hospital admission rate for the period
      2010-2011 was 40/1,000 enrolled. Women, elderly and those belonging to the lowest
      caste had a higher hospitalisation rate. Forty four per cent of patients who had
      enrolled in RSBY and had used the RSBY card still faced OOP payments at the time
      of hospitalisation. The median OOP payment for the above patients was US$ 80
      (interquartile range, $16-$200) and was similar in both government and private
      hospitals. Patients incurred OOP payments mainly because they were asked to
      purchase medicines and diagnostics, though the same were included in the benefit
      package. CONCLUSIONS: While the RSBY has managed to include the poor under its
      umbrella, it has provided only partial financial coverage. Nearly 60% of insured
      and admitted patients made OOP payments. We plea for better monitoring of the
      scheme and speculate that it is possible to enhance effective financial coverage
      of the RSBY if the nodal agency at state level would strengthen its stewardship
      and oversight functions.

PMID- 23961957
TI  - Hydrogen ion concentration and coronary artery bypass graft surgery with and
      without cardiopulmonary bypass.
AB  - BACKGROUND: Acidosis during cardiopulmonary bypass (CPB) has been related to the
      strong ion difference (SID) and the composition of intravascular fluids that are
      administered. Less intravascular fluids tend to be administered during off- than
      on-pump CABG and should influence the degree of acidosis that develops. This
      study aimed to explore the role of CPB in the development of acidosis by
      comparing changes in hydrogen ion concentration ([H+]) and electrolytes in
      patients undergoing on- and off-pump coronary artery bypass graft (CABG) surgery.
      METHODS: Eighty two patients had arterial blood gas measurements pre-operatively,
      following CABG and at approximately 0600 h the morning after surgery. Carbon
      dioxide tension (PaCO2) and concentrations of sodium, potassium, chloride, [H+],
      bicarbonate and haemoglobin were measured and strong ion difference calculated.
      Data was analysed using mixed repeated-measures analysis of variance. RESULTS:
      Intra-operatively, mean SID decreased more in the on- compared to the off-pump
      group (4.0 mmol/L, 95% confidence interval 2.8-5.3 mmol/L, p < 0.001). Neither
      [H+] or PaCO2 changed significantly and there were no significant difference
      between the groups. By the morning following surgery, [H+] and PaCO2 had both
      increased (p < 0.001) and difference in SID had disappeared (p = 0.17).
      CONCLUSION: Despite significant differences in changes in SID, there were no
      differences in [H+] between patients during or after CABG surgery whether
      performed on- or off-pump. This may be have been the result of greater
      haemodilution in the on- compared to the off-pump group, compensating for change
      in SID by reducing the concentration of weak acids. Although it was associated
      with significantly greater decrease in SID, CPB was not associated with any
      significant increased risk of acidosis.

PMID- 23961959
TI  - Virtual reality Stroop task for assessment of supervisory attentional processing.
AB  - The current project is a preliminary attempt at assessing the potential of a
      three-dimensional virtual reality Stroop task (VRST) for investigation of
      supervisory attentional processing. The VRST was compared with paper-and-pencil
      and computer automated (two-dimensional) versions of the Stroop.
      Psychophysiological measures were also used to assess varying levels of user
      arousal. The three versions of the Stroop task were conducted with a sample of 50
      healthy university students, between the ages of 18 and 28 years, which included
      equivalent distributions of men and women from ethnically diverse populations. No
      significant differences were found for age, gender, or education. Results
      indicated that the typical Stroop effect pattern found in the Delis-Kaplan
      Executive Function System (D-KEFS) and Automated Neuropsychological Assessment
      Metrics (ANAM) occurs in the VRST; the complexity condition of the VRST offers
      potential for assessment of exogenous and endogenous attentional processing; the
      two single-item presentation formats of the Stroop are comparable; there is a
      psychophysiological difference in arousal between low- and high-threat zones; and
      while there is a learning effect present in the VRST across conditions, it is
      limited by the arousal conditions in the high-threat zones. Additionally, no
      negative side effects were associated with use of the virtual environment. We
      conclude that the VRST has the potential to offer a novel approach to assessment
      of supervisory attentional processing within an ecologically relevant
      environment. 

PMID- 23961958
TI  - Proteomic analysis of extremely severe hand, foot and mouth disease infected by
      enterovirus 71.
AB  - BACKGROUND: To clarify the molecular mechanisms that participate in the severe
      hand, foot and mouth disease (HFMD) infected by Enterovirus 71 and to detect any
      related protein biomarkers, we performed proteomic analysis of protein extracts
      from 5 extremely severe HFMD children and 5 healthy children. METHODS: The
      protein profiles of them were compared using two-dimensional electrophoresis.
      Differentially expressed proteins were identified using mass spectrometry.
      Functional classifications of these proteins were based on the PANTHER. The
      interaction network of the differentially expressed protein was generated with
      Pathway Studio. RESULTS: A total of 38 differentially expressed proteins were
      identified. Functional classifications of these proteins indicated a series of
      altered cellular processes as a consequence of the severe HFMD. These results
      provided not only new insights into the pathogenesis of severe HFMD, but also
      implications of potential therapeutic designs. CONCLUSIONS: Our results suggested
      the possible pathways that could be the potential targets for novel therapy:
      viral protection, complement system and peroxide elimination.

PMID- 23961960
TI  - Cancer in Australia: Actual incidence data from 1991 to 2009 and mortality data
      from 1991 to 2010 with projections to 2012.
AB  - AIMS: The Australian Institute of Health and Welfare (AIHW) is a major national
      agency established by the Australian government to provide information and
      statistics on Australia's health and welfare. The AIHW and the Australasian
      Association of Cancer Registries collaborate every year to provide updated
      information on cancer occurrences and trends in Australia. METHOD: Actual number
      of cases and deaths is presented together with age-standardized rates for all
      cancers combined and selected cancer sites from 1991 to 2009 for incidence and
      from 1991 to 2010 for mortality, with projections to 2012. Differences in
      incidence and mortality rates according to age, Indigenous status and remoteness
      areas are also provided. In addition, information on hospitalizations due to
      cancer, palliative care and participation in Australia's national screening
      programs for breast, cervical and bowel cancer is presented. RESULTS: In 2012, it
      was estimated that 120 710 new cases of cancer (excluding basal and squamous cell
      carcinoma of the skin) were diagnosed. Prostate cancer was estimated to be the
      most commonly diagnosed cancer in males, while breast cancer was estimated to be
      the most commonly diagnosed cancer in females. In 2010, more than 42 800 deaths
      from cancer occurred in Australia. Lung cancer was by far the most common cause
      of cancer death in both males and females. CONCLUSION: In the last decade, cancer
      incidence rates increased in males and stabilized in females, while mortality
      rates decreased steadily. The overall incidence and mortality rates of cancer for
      Indigenous Australians were higher than for non-Indigenous Australians.

PMID- 23961961
TI  - Calculating sample size estimates for RNA sequencing data.
AB  - BACKGROUND: Given the high technical reproducibility and orders of magnitude
      greater resolution than microarrays, next-generation sequencing of mRNA (RNA-Seq)
      is quickly becoming the de facto standard for measuring levels of gene expression
      in biological experiments. Two important questions must be taken into
      consideration when designing a particular experiment, namely, 1) how deep does
      one need to sequence? and, 2) how many biological replicates are necessary to
      observe a significant change in expression? RESULTS: Based on the gene expression
      distributions from 127 RNA-Seq experiments, we find evidence that 91% +/- 4% of
      all annotated genes are sequenced at a frequency of 0.1 times per million bases
      mapped, regardless of sample source. Based on this observation, and combining
      this information with other parameters such as biological variation and technical
      variation that we empirically estimate from our large datasets, we developed a
      model to estimate the statistical power needed to identify differentially
      expressed genes from RNA-Seq experiments. CONCLUSIONS: Our results provide a
      needed reference for ensuring RNA-Seq gene expression studies are conducted with
      the optimally sample size, power, and sequencing depth. We also make available
      both R code and an Excel worksheet for investigators to calculate for their own
      experiments.

PMID- 23961962
TI  - Worldwide relation between the number of McDonald's restaurants and the
      prevalence of obesity.

PMID- 23961963
TI  - Erratum.

PMID- 23961964
TI  - Learning the direction and extent of a movement.
AB  - The hypotheses (a) that the memory trace and perceptual trace are independent
      memory states and (b) that they develop as a positive function of the amount of
      practice on the criterion movement were tested. The criterion movement studied
      was a linear displacement of a stylus in two dimensions (direction and extent) in
      the horizontal plane. The experiment had two phases: 92 acquisition trials with
      knowledge of results (KR) and 20 transfer trials without KR. Four groups of 10
      male and female college students performed the acquisition trials under one of
      four movement conditions: (a) criterion extent and criterion direction, (b)
      criterion extent and varied direction, (c) varied extent and criterion direction,
      and (d) varied extent and varied direction. The data, showing support for the
      assumption and the hypothesis under test, were interpreted as evidence in favor
      of Adams' (1971) closed-loop theory of motor learning. 

PMID- 23961965
TI  - The performance of intellectually normal and educable mentally retarded boys on
      tests of throwing accuracy.
AB  - Educable retarded (n =71) and intellectually normal (n =71) boys were measured
      for both vertical and horizontal errors on an overarm throwing task. The accuracy
      of throwing errors in terms of the total variance about the target of the
      intellectually normal boys was superior to that of the retarded boys. Variable
      errors and constant errors (absolute values) of the retarded boys were greater
      than those measures for the normals. The relative contributions of variable error
      to the total variance of the retarded boys were not substantially greater on
      either horizontal or vertical measures than were those for the normals. These
      findings did not support the variability hypothesis (Baumeister, 1968) which
      states that variable error contributes more to the performance levels of retarded
      than of normals. 

PMID- 23961966
TI  - Interaction of sex and task differences in reminiscence.
AB  - Reminiscence values obtained from 84 subjects on two tracking tasks were examined
      for their dependence upon sex, task, task order, and repeated measurement within
      tasks. Females reminisced more than males on both tasks, while task differences
      were significant only for males. These effects (a) show that reminiscence is a
      more complexly determined phenomenon than most writers have assumed, and (b)
      argue for a broadcast empirical examination of other possible dependencies. 

PMID- 23961967
TI  - Planning and efferent components in the coding of movement.
AB  - Two experiments were carried out to assess the cognitive contribution of a
      movement plan and its relationship to efferent-command information in explaining
      the superior accuracy of preselected movement. Subjects performed under
      conditions which differed with regard to efferent information (active versus
      passive) and the availability of a movement plan (preselected, subject defined
      vs. constrained, experimenter defined). In both experiments active preselection
      had significantly smaller reproduction errors than any other combination,
      indicating that the planning process in itself was insufficient to facilitate
      movement coding. The findings were interpreted in terms of the sometimes
      synonymously viewed concepts of central monitoring of efference, efference copy,
      and corollary discharge. The latter notion, that a central signal occurs prior to
      movement which acts to facilitate the processing of information, seemed to
      provide the most appropriate account of the present data. The experiments
      reported here are a portion of a Ph.D. dissertation submitted to the University
      of Wisconsin-Madison under the supervision of George E. Stelmach, to whom
      appreciation is extended. Support for the research was provided by Grant MH 22081
      01 from the National Institute of Mental Health and by Grant NE-G-3-0009 from the
      National Institute of Education. However, the opinions expressed herein do not
      necessarily reflect the position or policies of the above granting agencies and
      no official endorsement of them should be inferred. The author would like to
      thank Shelley Smith who assisted with data collection in these experiments. 

PMID- 23961968
TI  - The relationship between the sequencing and timing components of a skill.
AB  - The relationship between the sequencing and timing components of a skill was
      investigated in a serial reaction-time task. Two groups received extensive
      training on an identical sequence of events. For one group there was a constant
      timing interval between events, while in the other group the length of the timing
      interval varied from trial to trial. Following training, the sequence was
      occasionally broken by an event occurring out of its proper order or time.
      Although there was no difference between the two groups in the speed of
      responding to unexpected events, the group for which timing was an integral part
      of the skill showed higher error rates to certain types of unpredictable event.
      The results suggest that relative timing is an integral part of the motor program
      representation. The research reported in this paper is part of a Ph.D. thesis
      submitted to the University of Oregon under the direction of S. W. Keele,
      supported by an Office of Naval Research Contract No. N00014-67-A-0446-004 to
      S.W. Keele. 

PMID- 23961969
TI  - Release from proactive and retroactive interference in motor short-term memory.
AB  - Six groups of 12 subjects participated in an experiment designed to test whether
      proactive and retroactive interference could be developed in a linear ' arm
      positioning task. The experiment also investigated the possibility of a release
      from these interfering sources as a result of a change in the direction of
      movement. The results supported the hypotheses that these forms of interference
      are produced by interpolated or preceding movement experience, and that a release
      from interference can occur with a change of direction of movement. The results
      were interpreted as producing an alternative method for identifying relevant
      encoding characteristics in motor short-term memory. 

PMID- 23961970
TI  - Timing and anticipation.
AB  - The present study examined the development of timing and coincident anticipation,
      whereby subjects moved a slide control to direct a cursor to intercept a target.
      An equal number of males and females (N=120 each) comprised the following age
      groups: 6-7, 8-9, 10-11, 12-13, 14-15, and 18-19 yr. Age, sex, and trials
      constituted the independent variables, with dependent measures of absolute,
      constant, and variable error. Each person completed60 trials, with complete
      target view present in the first 40 trials. The target disappeared from view
      shortly after initial movement in Trials 41-60. Each older age group performed,
      with less error than the next younger age group, with the exception of the equal
      skill level of the two oldest groups. Males outperformed females, and target
      masking resulted in significant decrements in performance. Information processing
      mechanisms that may be responsible are discussed. 

PMID- 23961971
TI  - A Developmental Explanation For Children's Motor behavior.
AB  - Two experiments were conducted to test the application of Pascual-Leone's (1970)
      neo-Piagetian theory for explaining children's acquisition of skill in a
      curvilinear positioning task. Two groups of children (late pre-operational 6 yr
      olds and early concrete 8 yr olds) were identified and from each group 10 low M
      processors and 10 high M-processors were selected (total n=40) through use of the
      Children's Embedded Figures Test. The 6 yr olds were administered 2-and 3-scheme
      curvilinear positioning tasks while the 8 yr olds performed 3-and 4-scheme tasks.
      The difference between the two experiments was the nature of the positioning
      tasks, i.e., one task allowed visual processing of information, while the other
      did not. Both experiments supported the neo-Piagetian predictions of structural
      mental space as explaining the developmental nature of motor skill acquisition,
      and functional mental space as explaining individual differences within stages in
      children's performance. 

PMID- 23961972
TI  - Influence of response similarity on interference in perceptual motor learning.
AB  - Motor interference was measured in terms of average response time in sorting 15
      pairs of cards, each pair containing words which were either unrelated or
      identical but printed in different colors. The two words of each pair were used
      in labeling two cubicles in such a way that they were apart by 0, 1, 2, or 3
      intervening cubicles in quasirandomly chosen directions. Interference was
      inversely related to response similarity, but this relationship may not appear in
      the absence of sufficient stimulus similarity. The findings are interpreted in
      the light of a hypothesis which views motor interference as a tendency for
      responses to deflect from their own courses and be pulled towards those of other
      responses with which they are at conflict. 

PMID- 23961974
TI  - Social network analysis as a metric for the development of an interdisciplinary,
      inter-organizational research team.
AB  - The development of an interdisciplinary and inter-organizational research team
      among eight of Canada's leading emergency, geriatric medicine and rehabilitation
      researchers affiliated with six academic centers has provided an opportunity to
      study the development of a distributed team of interdisciplinary researchers
      using the methods of social network theory and analysis and to consider whether
      these methods are useful tools in the science of team science. Using traditional
      network analytic methods, the team of investigators were asked to rate their
      relationships with one another retrospectively at one year prior to the team's
      first meeting and contemporaneously at two subsequent yearly intervals. Using
      network analytic statistics and visualizations the data collected finds an
      increase in network density and reciprocity of relationships together with more
      distributed centrality consistent with the findings of other researchers. These
      network development characteristics suggest that the distributed research team is
      developing as it should and supports the assertion that network analysis is a
      useful science of team science research tool.

PMID- 23961973
TI  - Plasmonic photothermal heating of intraperitoneal tumors through the use of an
      implanted near-infrared source.
AB  - Plasmonic nanomaterials including gold nanorods are effective agents for inducing
      heating in tumors. Because near-infrared (NIR) light has traditionally been
      delivered using extracorporeal sources, most applications of plasmonic
      photothermal therapy have focused on isolated subcutaneous tumors. For more
      complex models of disease such as advanced ovarian cancer, one of the primary
      barriers to gold nanorod-based strategies is the adequate delivery of NIR light
      to tumors located at varying depths within the body. To address this limitation,
      a series of implanted NIR illumination sources are described for the specific
      heating of gold nanorod-containing tissues. Through computational modeling and ex
      vivo studies, a candidate device is identified and validated in a model of
      orthotopic ovarian cancer. As the therapeutic, imaging, and diagnostic
      applications of plasmonic nanomaterials progress, effective methods for NIR light
      delivery to challenging anatomical regions will complement ongoing efforts to
      advance plasmonic photothermal therapy toward clinical use. 

PMID- 23961975
TI  - Narrowband ultraviolet B irradiation increases the serum level of vitamin D3 in
      patients with neurofibromatosis 1.
AB  - The serum vitamin D3 levels in patients with neurofibromatosis 1 has been
      reported to be significantly lower than that in control subjects, and the level
      of vitamin D3 reversely correlates with the severity of neurofibroma formation.
      We found that narrowband ultraviolet B (NB-UVB) irradiation increased the serum
      level of 1,25(OH)2 vitamin D3 in patients with neurofibromatosis 1. The
      difference in the 1,25(OH)2 vitamin D3 levels between patients who had received
      irradiation for more than 18 months and those who had no irradiation was highly
      significant. Time-course analyses of the serum vitamin D3 levels in the patients
      who were enrolled after informed consent revealed that the levels became higher
      significantly after 6 months of irradiation. It is suggested that NB-UVB
      irradiation is effective for increasing the serum level of vitamin D3 in patients
      with neurofibromatosis 1, which may be of benefit for skin symptoms such as
      pigmented macules or neurofibromas.

PMID- 23961976
TI  - Efficient 3D porous microstructure reconstruction via Gaussian random field and
      hybrid optimization.
AB  - Obtaining an accurate three-dimensional (3D) structure of a porous microstructure
      is important for assessing the material properties based on finite element
      analysis. Whereas directly obtaining 3D images of the microstructure is
      impractical under many circumstances, two sets of methods have been developed in
      literature to generate (reconstruct) 3D microstructure from its 2D images: one
      characterizes the microstructure based on certain statistical descriptors,
      typically two-point correlation function and cluster correlation function, and
      then performs an optimization process to build a 3D structure that matches those
      statistical descriptors; the other method models the microstructure using
      stochastic models like a Gaussian random field and generates a 3D structure
      directly from the function. The former obtains a relatively accurate 3D
      microstructure, but computationally the optimization process can be very
      intensive, especially for problems with large image size; the latter generates a
      3D microstructure quickly but sacrifices the accuracy due to issues in numerical
      implementations. A hybrid optimization approach of modelling the 3D porous
      microstructure of random isotropic two-phase materials is proposed in this paper,
      which combines the two sets of methods and hence maintains the accuracy of the
      correlation-based method with improved efficiency. The proposed technique is
      verified for 3D reconstructions based on silica polymer composite images with
      different volume fractions. A comparison of the reconstructed microstructures and
      the optimization histories for both the original correlation-based method and our
      hybrid approach demonstrates the improved efficiency of the approach. 

PMID- 23961977
TI  - An investigation of the genetic diversity of the Kerkennah islands and Mahdia
      (Tunisia) using biparental markers.
AB  - BACKGROUND: Kerkennah is one of the main inhabited islands of Tunisia. The origin
      of the population of Kerkennah has not been established and no well-defined
      ethnic groups have been identified nor are genetic studies available. Mahdia, a
      Tunisian coastal city, has a long history dating back to ancient times. AIM: To
      discover the genetic diversity of the two studied populations and analyse their
      relationships with other Mediterranean populations. SUBJECT AND METHODS: Seven
      human-specific Alu insertion polymorphisms were typed in 99 individuals born in
      Kerkennah and Mahdia. RESULTS: A neighbour-joining tree and MDS multidimensional
      scaling analysis showed that these Tunisian populations are scattered amongst
      North African and Europeans populations, indicating their high genetic diversity
      and mosaic aspect. The important finding of this study was the proximity of
      Kerkennah to Moroccans. Hence, the actual gene pool of this insular population
      may descend from the ancestral population known to be of Moroccan origin.
      Concerning Mahdia, its closeness to Eurasian populations and some Tunisian groups
      reflected a high Eurasian genetic component for North African populations and
      confirmed their heterogeneity. CONCLUSION: The strategic location of the two
      studied populations and their fortifications have allowed them to play a leading
      role in the Mediterranean basin.

PMID- 23961978
TI  - Hot melt extrusion for amorphous solid dispersions: temperature and moisture
      activated drug-polymer interactions for enhanced stability.
AB  - Hot melt extrudates (HMEs) of indomethacin (IND) with Eudragit EPO and Kollidon
      VA 64 and those of itraconazole (ITZ) with HPMCAS-LF and Kollidon VA 64 were
      manufactured using a Leistritz twin screw extruder. The milled HMEs were stored
      at controlled temperature and humidity conditions. The samples were collected
      after specified time periods for 3 months. The stability of amorphous HMEs was
      assessed using moisture analysis, thermal evaluation, powder X-ray diffraction,
      FTIR, HPLC, and dissolution study. In general, the moisture content increased
      with time, temperature, and humidity levels. Amorphous ITZ was physically
      unstable at very high temperature and humidity levels, and its recrystallization
      was detected in the HMEs manufactured using Kollidon VA 64. Although physical
      stability of IND was better sustained by both Eudragit EPO and Kollidon VA 64,
      chemical degradation of the drug was identified in the stability samples of HMEs
      with Eudragit EPO stored at 50  degrees C. The dissolution rates and the
      supersaturation levels were significantly decreased for the stability samples in
      which crystallization was detected. Interestingly, the supersaturation was
      improved for the stability samples of IND:Eudragit EPO and ITZ:HPMCAS-LF, in
      which no physical or chemical instability was observed. This enhancement in
      supersaturation was attributed to the temperature and moisture activated
      electrostatic interactions between the drugs and their counterionic polymers. 

PMID- 23961980
TI  - Can we lose memory for music? A case of music agnosia in a nonmusician.
AB  - Abstract A follow-up study of a patient, C.N., with a severe auditory agnosia
      limited to music is reported. After bilateral temporal lobe damage, C.N., whose
      cognitive and speech functions are otherwise normal, is totally unable to
      identify or to experience a sense of familiarity with musical excerpts that were
      once highly familiar to her. However, she can recognize the lyrics that usually
      accompany the songs. She can also identify familiar sounds, such as animal cries.
      Thus, her agnosia appears highly specific to music. The functional nature of her
      deficit has been investigated through various perceptual tasks. She was initially
      severely impaired in processing pitch sequential structure but has always enjoyed
      normal processing of temporal structure. This selective disturbance for
      sequential pitch information can hardly account for her tune agnosia since
      processing of pitch variations has dramatically improved over the years. This
      recovery was not accompanied by any signs of improvement in music recognition,
      which remains extremely poor. Moreover, the fact that she has never been able to
      hum tunes from memory argues for a basic memory disturbance. Thus, she was tested
      here with a series of tests aiming at assessing her memory for familiar and
      unfamiliar music. The results show that C.N. has now recovered most perceptual
      skills and that despite a transient ability to exhibit knowledge of familiar
      music under restricted circumstances, she is markedly impaired at naming a tune
      and at judging its familiarity, as well as at memorizing familiar as well as
      novel music. This deficit was found to be not only modality-specific but music
      specific as well. The findings suggest the existence of a perceptual memory that
      is specialized for music and that can be selectively damaged so as to prevent
      most forms of recognition ability. 

PMID- 23961979
TI  - Neurocognitive outcomes at kindergarten entry after liver transplantation at <3
      yr of age.
AB  - This prospective inception cohort study determines kindergarten-entry
      neurocognitive abilities and explores their predictors following liver
      transplantation at age <3 yr. Of 52 children transplanted (1999-2008), 33 (89.2%)
      of 37 eligible survivors had psychological assessment at age 54.7 (8.4) months:
      21 with biliary atresia, seven chronic cholestasis, and five acute liver failure.
      Neurocognitive scores (mean [s.d.], 100 [15]) as tested by a pediatric
      experienced psychologist did not differ in relation to age group at transplant
      (<=12 months and >12 months): FSIQ, 93.9 (17.1); verbal (VIQ), 95.3 (16.5);
      performance (PIQ), 94.3 (18.1); and VMI, 90.5 (15.9), with >70% having scores
      >=85, average or above. Adverse predictors from the pretransplant, transplant,
      and post-transplant (30 days) periods using univariate linear regressions for
      FSIQ were post-transplant use of inotropes, p = 0.029; longer transplant warm
      ischemia time, p = 0.035; and post-transplant highest serum creatinine, (p =
      0.04). For PIQ, they were pretransplant encephalopathy, p = 0.027; post
      transplant highest serum creatinine, p = 0.034; and post-transplant inotrope use,
      p = 0.037. For VMI, they were number of post-transplant infections, p = 0.019;
      post-transplant highest serum creatinine, p = 0.025; and lower family
      socioeconomic index, p = 0.039. Changes in care addressing modifiable predictors,
      including reducing acute post-transplant illness, pretransplant encephalopathy,
      transplant warm ischemia times, and preserving renal function, may improve
      neurocognitive outcomes. 

PMID- 23961981
TI  - Enhancement of perceived visual intensity by auditory stimuli: a psychophysical
      analysis.
AB  - Abstract Judgments of the intensity of a stimulus are dependent on the level of
      central nervous system activity it generates. Generally, it is assumed that such
      judgments are based on activity along modality-specific pathways. Thus, visual
      intensity judgments would be based on unimodal visual activity. However, many
      neurons do not fit neatly within modality-specific categories, but can be
      influenced by more than one sensory modality. Often the "multisensory" effect is
      quite pronounced. If these multisensory neurons participate in such fundamental
      functions as perceived intensity, the presence of a nonvisual (i.e., auditory)
      cue may have a significant effect on the perceived intensity of a visual cue. The
      results of the present study were consistent with such a hypothesis. A brief,
      broad-band auditory stimulus was found to significantly enhance the perceived
      intensity of an LED. The effect was most pronounced at the lowest visual
      intensities, and was evident regardless of the location of the auditory cue.
      However, it was present only at the location of visual fixation. Yet, despite the
      significant influence of the auditory cue, and its differential effect at
      different visual intensities, a power function that maintains the proportionality
      among perceived visual intensities was retained. 

PMID- 23961982
TI  - On the language specificity of the brain response to syntactic anomalies: is the
      syntactic positive shift a member of the p300 family?
AB  - Abstract Event-related brain potentials (ERPs) were recorded from 13 scalp
      electrodes while subjects read sentences, some of which contained either a verb
      that disagreed in number with the subject noun (syntactic anomaly) or a word in
      uppercase letters (physical anomaly). Uppercase words elicited the P300 complex
      of positivities, whereas agreement violations elicited a late positive shift with
      an onset around 500 msec and a duration of several hundred msec. These effects
      differed in their morphology, temporal course, amplitude, and scalp distribution.
      Furthermore, manipulations of the probability-of-occurrence and task relevance of
      the anomalies had robust effects on the response to uppercase words, but not on
      the response to agreement violations. Finally, these anomalies had additive
      effects when agreement-violating uppercase (doubly anomalous) words were
      presented. These results are taken to be an initial indication that the positive
      shift elicited by agreement violations is distinct from the P300 response to
      unexpected, task-relevant anomalies that do not involve the violation of a
      grammatical rule. 

PMID- 23961983
TI  - A neural mechanism for involuntary attention shifts to changes in auditory
      stimulation.
AB  - Abstract Involuntary switching to task-irrelevant sound change was studied by
      measuring event-related brain potentials (ERPs) and behavioral performance in a
      dichotic listening paradigm. Pairs of tones (S1 and S2) were presented and
      subjects were instructed to ignore S1 (delivered to the left ear) and to make a
      go/no-go response to the subsequent S2 (delivered to the right ear). On most
      trials, the task-irrelevant S1 was of standard frequency, but occasionally it
      deviated from the standard frequency either by a small or large amount. It was
      predicted that deviant stimuli were automatically detected and that they could
      involuntarily capture attention. If they lead to attention switching, less
      capacity should be available for the processing of target tones resulting in
      impaired processing of S2. As in many previous studies, deviant tones elicited
      the mismatch negativity (MMN), which is a component of the ERP indicating
      automatic change detection. Furthermore, targets preceded by a deviant tone
      elicited a smaller N1 wave and were detected less effectively than targets
      preceded by a standard tone. This impaired processing of targets following task
      irrelevant changes occurred only with short S1-S2 intervals (Experiment I) but
      not with long ones (Experiment II). The results support a model claiming that the
      auditory system possesses a change detection system that monitors the acoustic
      input and may produce an attentional "interrupt" signal when a deviant occurs.
      The involuntary attentional capture caused by this signal leads to impoverished
      processing of closely succeeding stimuli. 

PMID- 23961984
TI  - Object-centered attentional biases in the intact brain.
AB  - Abstract By simulating neglect-like effects in neurologically intact observers,
      we evaluated whether normal attentional allocation can be object centered. In a
      series of three experiments, observers detected a small gap on the left or right
      side of a configuration presented in either the left of right visual field. The
      figures were positioned so that on different trials, the left and right sides
      would fall in the same retinotopic, hemispatial, and environmental location.
      Thus, only the location with respect to an object-centered frame varied. We found
      opposite patterns of bias within each visual field: For figures in the left
      visual field, left gaps were detected better than right gaps, whereas in the
      right visual field the opposite pattern was evident. Control conditions indicate
      that these biases are not due to masking from eccentric contours and depend on
      the left and right segments being united into a single form. These results
      indicate that opposing orientational biases of the left and right hemispheres can
      operate within an object-centered frame in the normal brain. This evidence
      converges with patient studies and single-unit electrophysiology to reveal the
      importance of a relatively late, abstract locus for visual selection. 

PMID- 23961985
TI  - MRI-Based Topographic Parcellation of Human Neocortex: An Anatomically Specified
      Method with Estimate of Reliability.
AB  - Abstract We describe a system of parcellation of the human neocortex, based upon
      magnetic resonance images, that conserves the topographic uniqueness of the
      individual brain. Subdivision of the neocortex, according to this system, is
      based entirely upon the configuration of a specified set of cerebral landmarks,
      principally neocortical fissures. These are present but unique in the details of
      their configurations in each individual brain. We introduce here a computer
      assisted algorithm that ensures that a skilled investigator can execute the
      parcellation routine in a manageable period of time. Secondly, we outline a
      comprehensive set of conventions that specify how the boundaries of parcellation
      units are defined by anatomic landmarks. The average interobserver agreement in
      voxel assignment to parcellation units within the overall neocortex was 80.2%. 

PMID- 23961986
TI  - A specific role for the right parahippocampal gyrus in the retrieval of object
      location: a positron emission tomography study.
AB  - Abstract A plethora of studies, across many species, have now demonstrated that
      the hippocampal region plays a critical role in memory for spatial location. In
      spite of this compelling evidence, a number of important neuropsychological and
      neuroanatomical issues remain unresolved. In the present study, the functional
      anatomy of object-location memory was investigated using positron emission
      tomography (PET) with magnetic resonance imaging (MRI). Regional cerebral blood
      flow (rCBF) was measured while normal volunteers encoded, and then retrieved, the
      locations of eight familiar objects presented on a computer screen. In two
      analogous conditions, designed to fractionate object-location memory into its
      component processes, the subjects were simply required to encode, and then to
      retrieve, eight distinct locations represented by identical white boxes on the
      screen. An increase in rCBF was observed in the region of the right
      parahippocampal gyrus corresponding to entorhinal cortex when the Retrieving
      Location condition was subtracted from the Retrieving Object-Location condition.
      In contrast, when the Encoding Location condition was subtracted from the
      Encoding Object-Location condition, no significant rCBF changes were observed in
      the hippocampal region although significant activation was observed, bilaterally,
      in the anterior fusiform gyrus. In addition, the two encoding conditions
      activated left-hemisphere regions preferentially, whereas the two retrieval
      conditions activated right-hemisphere regions. Together, these findings suggest
      that the human right hippocampal region is critically involved in retrieving
      information that links object to place. The secondary finding that encoding and
      retrieval appear to be lateralized to the left and right hemispheres
      respectively, is discussed with reference to current models of episodic memory,
      and alternative hypotheses are considered. 

PMID- 23961988
TI  - Editor's note.

PMID- 23961987
TI  - The role of neuronal synchronization in response selection: a biologically
      plausible theory of structured representations in the visual cortex.
AB  - Abstract Recent experimental results in the visual cortex of cats and monkeys
      have suggested an important role for synchronization of neuronal activity on a
      millisecond time scale. Synchronization has been found to occur selectively
      between neuronal responses to related image components. This suggests that not
      only the firing rates of neurons but also the relative timing of their action
      potentials is used as a coding dimension. Thus, a powerful relational code would
      be available, in addition to the rate code, for the representation of perceptual
      objects. This could alleviate difficulties in the simultaneous representation of
      multiple objects. In this article we present a set of theoretical arguments and
      predictions concerning the mechanisms that could group neurons responding to
      related image components into coherently active aggregates. Synchrony is likely
      to be mediated by synchronizing connections; we introduce the concept of an
      interaction skeleton to refer to the subset of synchronizing connections that are
      rendered effective by a particular stimulus configuration. If the image is
      segmented into objects, these objects can typically be segmented further into
      their constituent parts. The synchronization behavior of neurons that represent
      the various image components may accurately reflect this hierarchical clustering.
      We propose that the range of synchronizing interactions is a dynamic parameter of
      the cortical network, so that the grain of the resultant grouping process may be
      adapted to the actual behavioral requirements. It can be argued that different
      aspects of purposeful behavior rely on separable processes by which sensory input
      is transformed into adjustments of motor activity. Indeed, neurophysiological
      evidence has suggested separate processing streams originating in the primary
      visual cortex for object identification and sensorimotor coordination. However,
      such a separation calls for a mechanism that avoids interference effects in the
      presence of multiple objects, or when multiple motor programs are simultaneously
      prepared. In this article we suggest that synchronization between responses of
      neurons in both the visual cortex and in areas that are involved in response
      selection and execution might allow for a selective routing of sensory
      information to the appropriate motor program. 

PMID- 23961989
TI  - Multi-morbidity of non communicable diseases and equity in WHO Eastern
      Mediterranean countries.
AB  - INTRODUCTION: Non communicable diseases are the biggest cause of death worldwide.
      Beside mortality, these diseases also cause high rates of morbidity and
      disability. Their high prevalence is generally associated to multi-morbidity.
      Because they need costly prolonged treatment and care, non communicable diseases
      have social and economical consequences that affect individuals, households and
      the whole society. They raise the equity problem between and within countries.
      METHODS AND LIMITATIONS: This annotated bibliography is a systematic review on
      multimorbidy of non communicable diseases and health equity in WHO Eastern
      Mediterranean countries. Medline/PubMed, EMBASE and other sources were used to
      get peer reviewed papers dealing with the review theme. The words/strings used
      for search and inclusion criteria were: multimorbidity, comorbidity, equity, non
      communicable diseases, chronic diseases, WHO Eastern Mediterranean and Arab
      countries. BIBLIOGRAPHY WITH ANNOTATIONS: According to the inclusion criteria, 26
      papers were included in the present review. Generally, lack or paucity of
      publications was encountered in themes like headache, cancer and respiratory
      diseases. Of the 26 contributions selected, twelve dealt with comorbidity of
      depression and mental disorders with other chronic diseases. Another set of 11
      publications was devoted to multimorbidity of diabetes, cardiovascular diseases
      (CVDs), hypertension, metabolic syndrome and obesity. Considering association of
      multimorbidity and social determinants, this review shows that female gender, low
      income, low level of education, old age and unemployed/retired are the most
      exposed to multimorbidity. It should also be stressed that, geographically, no
      contribution was issued from North African countries.Non communicable diseases
      are one of the biggest challenges facing health decision makers in WHO Eastern
      Mediterranean countries where the multidimensional transition is boosting
      increases in multimorbidity of depression and mental diseases, cardiovascular
      diseases, diabetes, cancer and respiratory diseases among the whole population
      but with the highest burden among the least disadvantaged individuals or
      subpopulations. Health ministries in WHO Eastern Mediterranean countries should
      pay a particular attention to the association between equity and multimorbidity
      and opt for cost effective strategies based on early diagnosis and sensitisation
      for healthy diet, physical activity, no smoking and no alcohol.

PMID- 23961990
TI  - Developments around the bioactive diketopiperazines: a patent review.
AB  - INTRODUCTION: 2,5-Diketopiperazines (DKPs) are cyclic dipeptides from two amino
      acids with or without further structural modifications in DKP nucleus. These DKPs
      demonstrated attractive bioactive diversity and potential in drug discovery.
      AREAS COVERED: This review summarized those bioactive DKPs in patents, and
      provided the analysis of the structure types (N-substitution, secondary
      cyclization, isopentenylation, S-substitution, dehydrogenation, and dimerization)
      and bioactivities including anti-tumor, neuroprotective, immune and metabolic
      regulatory, oxytocin inhibitory and anti-inflammatory effects, antibiotic
      activity, PAF inhibition, inhibition of plasminogen activator and T-cell mediated
      immunity, and insecticidal activity, etc. EXPERT OPINION: Though DKPs did not
      show very complicated chemical structures, their rigid structure, chiral nature
      and varied side chains led to their various medicinal applications.

PMID- 23961991
TI  - Additional cytotoxic pyridoacridine alkaloids from the ascidian Cystodytes
      violatinctus and biogenetic considerations.
AB  - The extraction and purification of the bioactive extract of Cystodytes
      violatinctus (Solomon Islands) led to the isolation and identification of six
      pyridoacridine alkaloids. The structures of four new members of this family,
      shermilamine F (1), dehydrokuanoniamine F (2), and arnoamines C (3) and D (4),
      were elucidated on the basis of NMR and MS data and by comparison with data of
      known compounds isolated from this genus. A general hypothetical biogenetic
      pathway is then proposed for pyridoacridine alkaloids that contain a fused
      pyrrole ring. Comparison of the biological properties of the isolated alkaloids
      is also discussed. 

PMID- 23961992
TI  - Asian-type intravascular large B-cell lymphoma of the spleen and bone marrow with
      Hodgkin-like morphology and immunophenotype.

PMID- 23961993
TI  - Regulation of the transcriptional activation of the androgen receptor by the UXT
      binding protein VHL.
AB  - Loss and/or inactivation of the VHL (von Hippel-Lindau) tumour suppressor causes
      various tumours. Using a yeast two-hybrid system, we have identified the AR
      (androgen receptor) co-activator UXT (ubiquitously expressed transcript), as a
      VHL-interacting protein. GST pull-down and co-immunoprecipitation assays show
      that UXT interacts with VHL. In addition, UXT recruits VHL to the nucleus. VHL
      associates with the DBD (DNA-binding domain) and hinge domains of the AR and
      induces AR ubiquitination. Moreover, VHL interaction with the AR activates AR
      transactivation upon DHT (dihydrotestosterone) treatment. VHL knockdown inhibits
      AR ubiquitination and decreases transcriptional activation of the AR. Our data
      suggest that the VHL-UXT interaction and VHL-induced ubiquitination of AR
      regulate transcriptional activation of the AR. 

PMID- 23961994
TI  - Targeting therapy of hepatocellular carcinoma with doxorubicin prodrug PDOX
      increases anti-metastatic effect and reduces toxicity: a preclinical study.
AB  - BACKGROUND: This study was to investigate the effects and safety of cathepsin B
      cleavable doxorubicin (DOX)-prodrug (PDOX) for targeting therapy of metastatic
      human hepatocellular carcinoma (HCC) using DOX as a positive control drug.
      METHODS: The orthotopic nude mice model of highly metastatic HCC was established
      and the animals were randomized and treated with PDOX, DOX and saline,
      respectively. Hematology, biochemistry and tumor markers were studied. At
      autopsy, liver tumor weight and size, ascites, abdominal lymph nodes metastases,
      experimental peritoneal carcinomatosis index (ePCI), and tumor-host body weight
      ratio were investigated. Immunohistochemical studies and western blotting were
      done to investigate key molecules involved in the mechanism of action. RESULTS:
      Compared with Control, both PDOX and DOX could similarly and significantly reduce
      liver tumor weight and tumor volume by over 40%, ePCI values, retroperitoneal
      lymph node metastases and lung metastases and serum AFP levels (P < 0.05). The
      PDOX group had significantly higher WBC than the DOX group (P < 0.05), and higher
      PLT than Control (P < 0.05). Serum BUN and Cr levels were lower in the PDOX group
      than DOX and Control groups (P < 0.05). Compared with Control, DOX increased CK
      and CK-MB; while PDOX decreased CK compared with DOX (P < 0.05). Multiple spotty
      degenerative changes of the myocardium were observed in DOX-treated mice, but not
      in the Control and PDOX groups. PDOX could significantly reduce the Ki-67
      positive rate of tumor cells, compared with DOX and Control groups. PDOX produced
      the effects at least via the ERK pathway. CONCLUSION: Compared with DOX, PDOX may
      have better anti-metastatic efficacy and reduced side effects especially cardio
      toxicities in this HCC model.

PMID- 23961996
TI  - A catalase promoter variant rs1001179 is associated with visual acuity but not
      with primary angle closure glaucoma in Saudi patients.
AB  - BACKGROUND: To Investigate whether the g.4760C>T polymorphism in the promoter
      region of the catalase gene (CAT) is a risk factor for primary angle closure
      glaucoma (PACG) in the Saudi population. METHODS: 138 unrelated PACG patients and
      403 unrelated control subjects from Saudi Arabia were genotyped for a single
      nucleotide polymorphism (SNP; rs1001179; g.4760C>T) utilizing Taq-Man((r)) assay.
      The association between different genotypes and various clinical indices
      important for PACG was also investigated. RESULTS: The distribution of different
      genotypes was comparable between both study groups. The genotype "C/C" was
      predominant among cafses; 94 (68.1%) and controls; 289 (71.7%). Heterozygous
      genotype "C/T", was present in 41 (29.7%) of cases and 103 (25.6%) of controls,
      where the homozygous variant genotype was present in only 3 (2.2%) of cases and
      11 (2.7%) of the controls. The distribution of variant allele was similar in both
      study groups (p= 0.568). Interestingly, there was a trend of association between
      the type of the variant (homozygous variant, heterozygous and wildtype genotype)
      and one important parameter for PACG, which is visual acuity. The visual acuity
      increase was; 0.62 (+/-0.74), 0.88 (+/-0.88) and 1.27 (+/-0.95) in patients
      carrying the "C/C", "C/T" and "T/T" genotypes respectively, which was
      statistically significant in both ANOVA and pairwise individual T tests (p =
      0.022, 0.031 and 0.039) when compared to controls. CONCLUSIONS: This variant is
      possibly associated with visual acuity in PACG patients and thus had the
      potential to be used as a parameter for assessing PACG severity.

PMID- 23961995
TI  - Synaptic protein and pan-neuronal gene expression and their regulation by Dicer
      dependent mechanisms differ between neurons and neuroendocrine cells.
AB  - BACKGROUND: Neurons in sympathetic ganglia and neuroendocrine cells in the
      adrenal medulla share not only their embryonic origin from sympathoadrenal
      precursors in the neural crest but also a range of functional features. These
      include the capacity for noradrenaline biosynthesis, vesicular storage and
      regulated release. Yet the regulation of neuronal properties in early
      neuroendocrine differentiation is a matter of debate and the developmental
      expression of the vesicle fusion machinery, which includes components found in
      both neurons and neuroendocrine cells, is not resolved. RESULTS: Analysis of
      synaptic protein and pan-neuronal marker mRNA expression during mouse development
      uncovers profound differences between sympathetic neurons and adrenal chromaffin
      cells, which result in qualitatively similar but quantitatively divergent
      transcript profiles. In sympathetic neurons embryonic upregulation of synaptic
      protein mRNA follows early and persistent induction of pan-neuronal marker
      transcripts. In adrenal chromaffin cells pan-neuronal marker expression occurs
      only transiently and synaptic protein messages remain at distinctly low levels
      throughout embryogenesis. Embryonic induction of synaptotagmin I (Syt1) in
      sympathetic ganglia and postnatal upregulation of synaptotagmin VII (Syt7) in
      adrenal medulla results in a cell type-specific difference in isoform prevalence.
      Dicer 1 inactivation in catecholaminergic cells reduces high neuronal synaptic
      protein mRNA levels but not their neuroendocrine low level expression. Pan
      neuronal marker mRNAs are induced in chromaffin cells to yield a more neuron-like
      transcript pattern, while ultrastructure is not altered. CONCLUSIONS: Our study
      demonstrates that remarkably different gene regulatory programs govern the
      expression of synaptic proteins in the neuronal and neuroendocrine branch of the
      sympathoadrenal system. They result in overlapping but quantitatively divergent
      transcript profiles. Dicer 1-dependent regulation is required to establish high
      neuronal mRNA levels for synaptic proteins and to maintain repression of
      neurofilament messages in neuroendocrine cells.

PMID- 23961998
TI  - Mefloquine-oxazolidine derivatives: a new class of anticancer agents.
AB  - A series of 23 racemic mefloquine-oxazolidine derivatives, 4-[3
      (aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8
      bis(trifluoromethyl)quinolines, derived from (R*, S*)-(+/-)-mefloquine and
      arenealdehydes, have been evaluated for their activity against four cancer cell
      lines (HCT-8, OVCAR-8, HL-60, and SF-295). Good cytotoxicities have been
      determined with IC50 values ranging from 0.59 to 4.79 MUg/mL. In general
      compounds with aryl groups having strong electron-releasing substituents, such as
      HO and MeO, or electron-rich heteroaryl groups, for example imidazol-2-y-l, are
      active. However, other factors such as steric effects may play a role. As both
      the active and non-active conformations of the mefloquine-oxazolidine derivatives
      are similar, it is concluded that molecular conformations do not play a
      significant role either. This study is the first to evaluate mefloquine
      derivatives as antitumor agents. The mefloquine-oxazolidine derivatives are
      considered to be useful leads for the rational design of new antitumor agents. 

PMID- 23961997
TI  - A history of low birth weight alters recovery following a future head injury: a
      case series.
AB  - OBJECTIVE: Low birth weight (LBW; below 2500 grams) is a general risk factor for
      a variety of neurodevelopmental difficulties. However, these children may remain
      more vulnerable to neurologic and environmental insults occurring years later.
      This prospective case series reports on children who sustained a mild, moderate,
      or severe traumatic brain injury (TBI) in middle childhood but who had also been
      born with birth weights below 2500 grams. PARTICIPANTS: PARTICIPANTS were 14
      children with mild, moderate, or severe traumatic brain injury (TBI), 5 of whom
      had birth weights under 2500 grams (LBW) and 9 children with normal birth weight
      (NBW). All participants were drawn from a larger study on the long-term cognitive
      and behavioral impact of pediatric TBI and were matched on age, estimated
      socioeconomic status (SES), and severity of TBI (with NBW children actually
      having a slightly worse overall injury severity). RESULTS: At baseline, both
      groups exhibited similar scores on WJ-R Letter Word Identification and
      Calculations, Tower of London number solved, and CVLT-C total correct. Baseline
      group differences were observed on the CELF-III Formulated Sentences (NBW > LBW)
      and on the VABS Adaptive Behavior Composite and Socialization subdomain (LBW >
      NBW). Over 2 years, relative to the NBW group, the LBW group evidenced declines
      on both WJ-R subtests, CVLT-C total correct, CELF-III Formulated Sentences, and
      VABS Adaptive Behavior Composite and Socialization. CONCLUSIONS: Although
      preliminary in nature due to small sample size, findings suggest a history of LBW
      influences the recovery trajectory following childhood TBI. Academic and adaptive
      functioning and verbal memory appeared particularly affected.

PMID- 23961999
TI  - Comparative proteomic and metabolomic analysis of Staphylococcus warneri SG1
      cultured in the presence and absence of butanol.
AB  - The complete genome of the solvent tolerant Staphylococcus warneri SG1 was
      recently published. This Gram-positive bacterium is tolerant to a large spectrum
      of organic solvents including short-chain alcohols, alkanes, esters and cyclic
      aromatic compounds. In this study, we applied a two-dimensional liquid
      chromatography (2D-LC) mass spectrometry (MS) shotgun approach, in combination
      with quantitative 2-MEGA (dimethylation after guanidination) isotopic labeling,
      to compare the proteomes of SG1 grown under butanol-free and butanol-challenged
      conditions. In total, 1585 unique proteins (representing 65% of the predicted
      open reading frames) were identified, covering all major metabolic pathways. Of
      the 967 quantifiable proteins by 2-MEGA labeling, 260 were differentially
      expressed by at least 1.5-fold. These proteins are involved in energy metabolism,
      oxidative stress response, lipid and cell envelope biogenesis, or have chaperone
      functions. We also applied differential isotope labeling LC-MS to probe
      metabolite changes in key metabolic pathways upon butanol stress. This is the
      first comprehensive proteomic and metabolomic study of S. warneri SG1 and
      presents an important step toward understanding its physiology and mechanism of
      solvent tolerance. 

PMID- 23962000
TI  - Mycobacterium bovis BCG killed by extended freeze-drying induces an
      immunoregulatory profile and protects against atherosclerosis.
AB  - OBJECTIVES: Atherosclerosis is an inflammatory disease of the arterial wall that
      leads to myocardial infarction and stroke. Regulatory T cells (Tregs) and IL-10
      exert significant anti-atherogenic effects in experimental models of
      atherosclerosis by modulating vascular inflammation. We have previously shown
      that Mycobacterium bovis BCG killed by extended freeze-drying (EFD BCG) decreases
      lung and colon inflammation by recruiting IL-10-producing Tregs. Therefore, the
      aim of this study was to investigate the effect of EFD BCG on the development of
      atherosclerosis. DESIGN: We used two strains of atherosclerosis-prone mice: Ldlr(
      /-) (four or six EFD BCG injections) and Apoe(-/-) (six injections). RESULTS: In
      both models, EFD BCG significantly reduced the size of atherosclerotic lesions,
      increased IL-10 production and reduced the serum levels of pro-inflammatory
      cytokines (IL-6, IL-13, KC and tumour necrosis factor-alpha). Shortly after
      treatment with EFD BCG, the number of plasmacytoid dendritic cells (pDCs) and
      Foxp3(+) Tregs in the draining lymph nodes increased. EFD BCG also led to
      accumulation of Tregs, but not of pDCs in the spleen, and reduced activity of NF
      kappaB and increased activity of PPAR-gamma in both the spleen and vascular
      tissue of treated mice. CONCLUSION: EFD BCG has atheroprotective effects through
      IL-10 production and Treg expansion. These findings support a novel approach to
      the prevention and treatment of atherosclerosis.

PMID- 23962002
TI  - Hepatitis C virus NS5A protein modulates IRF-7-mediated interferon-alpha
      signaling.
AB  - Hepatitis C virus (HCV) establishes chronic infection in a large number of
      infected individuals. We have previously shown that HCV infection in hepatocytes
      blocks poly (I-C) or interferon (IFN)-alpha-mediated IRF-7 nuclear translocation
      (Raychoudhuri and others 2010). However, the mechanism of IRF-7 regulation by HCV
      remained unknown. In this study, we have observed that HCV NS5A physically
      associates with IRF-7. A subsequent study suggested that the HCV NS5A protein
      blocks IRF-7-mediated IFN-alpha14 promoter activation. Further analyses
      demonstrated that site-specific mutagenesis of the 2 basic arginine residues
      (amino acids Arg(216) and Arg(217)) in the NS5A is critical for IRF-7-mediated
      IFN-alpha14 promoter regulation. Together, our results suggested that the HCV
      NS5A protein limits the IFN-alpha-signaling pathway in association with IRF-7,
      and may, in part, be responsible for the establishment of chronic infection. 

PMID- 23962003
TI  - Site-specific PEGylation enhances the pharmacokinetic properties and antitumor
      activity of interferon beta-1b.
AB  - Interferon beta (IFN-beta) is widely used to ameliorate disease progression in
      patients with Multiple Sclerosis. IFN-beta has a short half-life in humans,
      necessitating frequent administration for optimum effectiveness. Covalent
      modification of IFN-beta with polyethylene glycol (PEG) improves the
      pharmacokinetic properties of the protein, but can adversely affect the protein's
      in vitro bioactivity. Random modification of lysine residues in IFN-beta with
      amine-reactive PEGs decreased the in vitro bioactivity of the protein 50-fold,
      presumably due to modification of lysine residues near critical receptor binding
      sites. PEGylated IFN-beta proteins that retained high in vitro bioactivity could
      be obtained by selective modification of the N-terminus of the protein with PEG.
      Here we use site-specific PEGylation technology (targeted attachment of a
      cysteine-reactive-PEG to an engineered cysteine residue in IFN-beta) to identify
      several additional amino acid positions where PEG can be attached to IFN-beta
      without appreciable loss of in vitro bioactivity. Unexpectedly, we found that
      most of the PEG-IFN-beta analogs showed 11- to 78-fold improved in vitro
      bioactivities relative to their unPEGylated parent proteins and to IFN-beta-1b.
      In vivo studies showed that a lead PEG-IFN-beta protein had improved
      pharmacokinetic properties compared to IFN-beta and was significantly more
      effective than IFN-beta at inhibiting growth of a human tumor xenograft in
      athymic mice. 

PMID- 23962005
TI  - Superior gluteal lymph node metastasis of melanoma.

PMID- 23962004
TI  - Microbial activation of gut dendritic cells and the control of mucosal immunity.
AB  - Current data support a role for gut colonization in maintaining balanced mucosal
      and systemic immune responses and have suggested aberrant innate immune
      recognition of enteric bacteria as an initiator of the adaptive immune damage
      associated with inflammatory bowel disease (Crohn's disease and ulcerative
      colitis). In fact, data from human studies and experimental mouse models have
      implicated transformation of the gut microbiota from a beneficial symbiotic state
      to one of imbalance or "dysbiosis" in the pathogenesis of several
      autoinflammatory diseases, including allergic skin and respiratory disorders,
      rheumatoid arthritis, type I diabetes, and colorectal cancer. The host has
      evolved to co-exist and maintain a mutualistic relationship with the commensal
      microbes of the gut, and it is the function of the host innate immune system to
      initiate and maintain this homeostasis, while retaining the ability to respond
      appropriately to pathogenic organisms. In this review, we discuss the molecular
      and cellular interactions of the mucosal immune system that decide this delicate
      balance of mutualism. Furthermore, we will highlight the role of dendritic cells
      in preserving this precarious balance and how gene products of commensal microbes
      may play an integral role in re-establishing this balance once it has gone awry. 

PMID- 23962006
TI  - Cell tracking using phase-adaptive shape prior.
AB  - Automated tracking of cell population is very crucial for quantitative
      measurements of dynamic cell-cycle behaviour of individual cells. This problem
      involves several subproblems and a high accuracy of each step is essential to
      avoid error propagation. In this paper, we propose a holistic three-component
      system to tackle this problem. For each phase, we first learn a mean shape as
      well as a model of the temporal dynamics of transformation, which are used for
      estimating a shape prior for the cell in the current frame. We then segment the
      cell using a level set-based shape prior model. Finally, we identify its phase
      based on the goodness-of-fit of the data to the segmentation model. This phase
      information is also used for fine-tuning the segmentation result. We evaluate the
      performance of our method empirically in various aspects and in tracking
      individual cells from HeLa H2B-GFP cell population. Highly accurate validation
      results confirm the robustness of our method in many realistic scenarios and the
      essentiality of each component of our integrating system. 

PMID- 23962007
TI  - Role of copper in photochemical damage to hair.
AB  - OBJECTIVE: The objective of this work was to identify whether low levels of redox
      metals such as copper will accelerate damage to hair on exposure to UV
      irradiation and whether this damage can be prevented. METHODS: The methods used
      were proteomics to measure the protein damage via protein loss after different
      periods of exposure and mass spectroscopy methods to identify specific marker
      peptides that are specifically created by this type of damage. RESULTS: In this
      work, we have developed new insights into the mechanism of UV damage using these
      proteomic methods. A marker fragment in the hair protein loss extract was
      identified (m/z = 1279) that is unique to UV exposure and increases with time of
      UV exposure. We have also identified for the first time in hair the role of
      exogenous copper in increasing UV damage both in terms of total protein
      degradation and also increased formation of the marker fragment and proposed a
      mechanism of action. It has been demonstrated that shampoo treatment containing a
      chelant such as N,N'-ethylenediamine disuccinic acid (EDDS) reduced copper
      accumulation in hair. CONCLUSION: This work provides evidence for the role of
      copper in UV-induced damage to hair and strategies to reduce copper levels in
      hair using a chelant such as EDDS.

PMID- 23962008
TI  - Intergenerational changes in birth parameters in Krakow (Poland) in the context
      of socio-economic transformation from 1985-2010.
AB  - BACKGROUND: Analyses of birth parameters worldwide reveal relatively high
      variability over time, often related to socioeconomic factors. AIM: The aim was
      to determine the existence of inter-generational changes in birth parameters in
      Krakow (Poland) in recent years and factors responsible. SUBJECTS AND METHODS:
      This research analysed data on 7800 newborns (e.g. body length and weight) and
      their parents in the years 1985-2010. The significance of differences was
      calculated using ANOVA. To examine the potential effect of environmental factors,
      MANOVA were used. RESULTS: In the case of birth weight no significant changes
      were observed. A significant decreasing tendency in birth length from the
      beginning of the 21st century was shown - this observation is quite rare.
      Accordingly, BMI increased significantly in the 2000s. A decreasing tendency was
      observed for head circumference. CONCLUSION: In the analysed period Poland
      experienced significant socio-economic changes, which could have partly
      contributed to the observed changes. Some of the observed trends in birth
      parameters are recent phenomena and it seems necessary to continue the research
      to confirm if these changes form a steady trend or are only temporary. Tracking
      any phenomena related to the development is important for the determination of
      disruptive factors and the reduction of their adverse effects.

PMID- 23962009
TI  - Vitamin D deficiency and insufficiency after pediatric liver transplantation.
AB  - Vitamin D deficiency and insufficiency are increasingly recognized in the general
      population, including healthy children. There is also an increasing emphasis on
      the importance of vitamin D status following pediatric liver transplantation and
      specifically its relationship to metabolic bone disease and growth retardation.
      Vitamin D insufficiency has also been associated with multiple immunological and
      metabolic disorders in adults. To our knowledge, this has not been systematically
      evaluated in children undergoing liver transplantation to date. Between October
      2004 and August 2008, serum 25-(OH)-vitamin D levels were measured in 199
      children who had undergone liver transplantation at Birmingham Children's
      Hospital. Potential factors contributing to vitamin D levels were evaluated.
      Additionally, we evaluated a possible relationship between vitamin D levels and
      immunological phenomena and metabolic complications. Median 25-(OH)-vitamin D
      level was 19.5 ng/mL (range: 4.4-71.4 ng/mL). A total of 105 children (53%) had
      insufficient vitamin D levels and 28 children (14%) showed vitamin D deficiency.
      The only factors found to be associated with vitamin D deficiency were season of
      sample, ethnicity, and PTH levels. Vitamin D deficiency was more prevalent during
      the first year after transplantation. We did not find a significant relationship
      between vitamin D levels and graft function or any other immunological and
      metabolic complications. Vitamin D insufficiency and deficiency are common in
      children after liver transplantation, especially in winter and spring and in non
      white patients. Initial post-transplant period and high PTH are significantly
      associated with vitamin D deficiency. Vitamin D status should be monitored
      following pediatric liver transplantation and vitamin D supplementation provided
      as required. 

PMID- 23962010
TI  - The end of the line for a brain-damaged model of unilateral neglect.
AB  - For more than a century, it has been known that damage to the right hemisphere of
      the brain can cause patients to be unaware of the contralesional side of space.
      This condition, known as unilateral neglect, represents a collection of
      clinically related spatial disorders characterized by the failure in free vision
      to respond, explore, or orient to stimuli predominantly located on the side of
      space opposite the damaged hemisphere. Recent studies using the simple task of
      line bisection, a conventional diagnostic test, have proven surprisingly
      revealing with respect to the spatial and attentional impairments involved in
      neglect. In line bisection, the patient is asked to mark the midpoint of a thin
      horizontal lie on a sheet of paper. Neglect patients generally transect far to
      the right of the center. Extensive studies of line bisection have been conducted,
      manipulating-among other factors-line length, orientation, and position. We have
      simulated the pattern of results using an existing computational model of visual
      perception and selective attention called MORSEL (Mozer, 1991). MORSEL has
      already been used to model data in a related disorder, neglect dyslexia (Mozer &
      Behrmann, 1990). In this earlier work, MORSEL was "lesioned" in accordance with
      the damage we suppose to have occurred in the brains of neglect patients. The
      same model and lesion can simulate the detailed pattern of performance on line
      bisection, including the following observations: (1) no consistent across-subject
      bias is found in normals; (2) transection displacements are proportional to line
      length in neglect patients; (3) variability of displacements is proportional to
      line length, in both normals and patients; (4) position of the lines with respect
      to the body or the page on which they are drawn has little effect; and (5) for
      lines drawn at different orientations, displacements are proportional to the
      cosine of the orientation angle. MORSEL fails to account for one observation:
      across patients, the variability of displacements for a particular line length is
      roughly proportional to mean displacement. Nonetheless, the overall fit of the
      model is sufficiently good that we believe MORSEL can be used as a diagnostic
      tool to characterize the specific nature of a patient's deficit, and thereby has
      potential down the line in therapy. 

PMID- 23962011
TI  - Residual Vision in Multiple Retinal Locations within a Scotoma: Implications for
      Blindsight.
AB  - There is an important new proposal that "blindsight"-the ability to detect and
      identify visual stimuli by forcedchoice guessing and in the absence of conscious
      awareness when they fall in blind regions of the visual field-is a function of
      residual "islands" of undamaged visual cortex. This stands in contrast to the
      widely accepted view that blindsight is exclusively a function of secondary
      visual pathways. According to the new view, residual vision in blindsight should
      be patchy. Thus, when apparently wide areas of residual vision in blindsight are
      found, these may be due to eye-movements that allow stimuli to pass over retinal
      locations corresponding to islands of sparing. We tested this hypothesis by
      examining the distribution of residual vision in blindsight when the effects of
      eye movements on the retinal location of stimuli were minimized. We report a
      series of experiments that examined twealternate forcedchoice discrimination in
      the blind field of the subject GY. Using a dual-Purkinje image eye-tracker we
      applied three methods of minimizing the effects of retinal slippage due to eye
      movements on discrimination performance: fixation stability-dependent trials,
      software image stabilization, and post hoc rejection of trials in which saccadic
      eye-movements were detected. In the first experiment, GY's discrimination
      performance was significantly above chance in 8 of 15 locations tested. In the
      subsequent experiments the subject knew the location of the target in each block
      of trials, and this resulted in improvements to performance in a further three
      locations. Increasing the luminance of the stimulus display (while maintaining
      95% target contrast), and increasing the temporal discriminability of the forced
      choice produced performance above chance in all but two of the locations tested.
      The consistent chance performance observed in two locations in the lower visual
      field nevertheless implies that GY's blindsight does not extend over the whole of
      his scotoma. Nevertheless, abolishing, or minimizing, the effects of eye
      movements did not result in a loss of detection in all the widely separated
      regions tested, and we thus conclude that GY's blindsight cannot adequately be
      explained in terms of islands of spared vision. Islands may account for residual
      vision in scotomata in some patients, but cannot be a universal account of the
      phenomenon of blindsight. 

PMID- 23962012
TI  - Islands of residual vision in hemianopic patients.
AB  - Following damage to primary visual cortex, some patients our initial findings.
      The data reveal a patchy distribution of redemonstrate a limited ability to
      respond to stimuli they do not sidual visual abilities in the absence of
      acknowledged awareness. acknowledge seeing. This residual vision, which has been
      referred to as "blindsight," has been attributed to secondary visual pathways. We
      previously reported an isolated island of blindsight in one patient and argued it
      was a likely consequence of cortical sparing in V1. We now report an extension of
      our initial findings. The data reveal a patchy distribution of residual visual
      abilities in the absence of acknowledged awareness. Variable patterns of cortical
      sparing appear to be the most parsimonious way to account for this outcome,
      suggesting that blindsight is generally mediated by the primary visual pathway. 

PMID- 23962013
TI  - Spatial transformations in the parietal cortex using basis functions.
AB  - Sensorimotor transformations are nonlinear mappings of sensory inputs to motor
      responses. We explore here the possibility that the responses of single neurons
      in the parietal cortex serve as basis functions for these transformations. Basis
      function decomposition is a general method for approximating nonlinear functions
      that is computationally efficient and well suited for adaptive modification. In
      particular, the responses of single parietal neurons can be approximated by the
      product of a Gaussian function of retinal location and a sigmoid function of eye
      position, called a gain field. A large set of such functions forms a basis set
      that can be used to perform an arbitrary motor response through a direct
      projection. We compare this hypothesis with other approaches that are commonly
      used to model population codes, such as computational maps and vectorial
      representations. Neither of these alternatives can fully account for the
      responses of parietal neurons, and they are computationally less efficient for
      nonlinear transformations. Basis functions also have the advantage of not
      depending on any coordinate system or reference frame. As a consequence, the
      position of an object can be represented in multiple reference frames
      simultaneously, a property consistent with the behavior of hemineglect patients
      with lesions in the parietal cortex. 

PMID- 23962014
TI  - Are the same attentional mechanisms used to detect visual search targets defined
      by color, orientation, and motion?
AB  - Motion information tends to be segregated from color and form information in the
      visual system, both perceptually and neuroanatomically, and it is therefore
      possible that different mechanisms of attention are used to select targets
      defined by these different feature types during visual search. To test this
      hypothesis, we recorded the N2pc component of the event-related potential
      waveform during visual search tasks with color, orientation, and motion targets.
      The N2pc component has previously been shown to reflect a specific attentional
      mechanism that is present for color and form targets, and we sought to determine
      whether this component would also be present for motion targets. The N2pc
      component was indeed observed for motion targets as well as color and orientation
      targets, consistent with the use of a common attentional mechanism across feature
      types. In addition, we found that motion singletons (i.e., individual items that
      moved in the opposite direction from the other items in the army) elicited an
      N2pc component even when they were task-irrelevant, indicating that motion
      discontinuities may produce an automatic orienting of attention. 

PMID- 23962015
TI  - Functional Neuroanatomy of Recall and Recognition: A PET Study of Episodic
      Memory.
AB  - The purpose of this study was to directly compare the brain regions involved in
      episodic-memory recall and recognition. Changes in regional cerebral blood flow
      were measured by positron emission tomography while young healthy test persons
      were either recognizing or recalling previously studied word pairs. Reading of
      previously nonstudied pairs served as a reference task for subtractive
      comparisons. Compared to reading, both recall and recognition were associated
      with higher blood flow (activation) at identical sites in the right prefrontal
      cortex (areas 47, 45, and 10) and the anterior cingulate. Compared to
      recognition, recall was associated with higher activation in the anterior
      cingulate, globus pallidus, thalamus, and cerebellum, suggesting that these
      components of the cerebello-frontal pathway play a role in recall processes that
      they do not in recognition. Compared to recall, recognition was associated with
      higher activation in the right inferior parietal cortex (areas 39, 40, and 19),
      suggesting a larger perceptual component in recognition than in recall. Contrary
      to the expectations based on lesion data, the activations of the frontal regions
      were indistinguishable in recall and recognition. This finding is consistent with
      the notion that frontal activations in explicit memory tasks are related to the
      general episodic retrieval mode or retrieval attempt, rather than to specific
      mechanisms of ecphory (recovery of stored information). 

PMID- 23962016
TI  - A Neural Dissociation within Language: Evidence that the Mental Dictionary Is
      Part of Declarative Memory, and that Grammatical Rules Are Processed by the
      Procedural System.
AB  - Language comprises a lexicon for storing words and a grammar for generating rule
      governed forms. Evidence is presented that the lexicon is part of a temporal
      parietalhnedial-temporal "declarative memory" system and that granlmatical rules
      are processed by a frontamasal-ganglia "procedural" system. Patients produced
      past tenses of regular and novel verbs (looked and plagged), which require an -ed
      suffixation rule, and irregular verbs (dug), which are retrieved from memory.
      Word-finding difficulties in posterior aphasia, and the general declarative
      memory impairment in Alzheimer's disease, led to more errors with irregular than
      regular and novel verbs. Grammatical difficulties in anterior aphasia, and the
      general impairment of procedures in Parkinson's disease, led to the opposite
      pattern. In contrast to the Parkinson's patients, who showed sup pressed motor
      activity and rule use, Huntington's disease patients showed excess motor activity
      and rule use, underscoring a role for the basal ganglia in grammatical
      processing. 

PMID- 23962017
TI  - Functional Neuroimaging of Cortical Dysfunction in Alcoholic Korsakoff's
      Syndrome.
AB  - Many neuropsychological investigations of human memory have focused on the
      amnesic deficits of alcoholic Korsakoff's syndrome. Structural neuroimaging
      suggests that the syndrome results from midline diencephalic damage, but
      functional neuroimaging has the potential to reveal additional neuropathology
      that may be responsible for cognitive dysfunction. Accordingly, high-resolution
      positron emission tomography (PET) was used to measure regional cerebral
      metabolic rates for glucose utilization in five alcoholic Korsakoff patients and
      nine alcoholic control subjects. Results from a continuous recognition test
      administered during the radiotracer uptake period indicated that all subjects
      performed normally with respect to immediate memory, whereas Korsakoff patients
      demonstrated a marked memory impairment in delayed recognition. PET results from
      the Korsakoff group showed a widespread decline in glucose metabolism in frontal,
      parietal, and cingulate regions, suggesting that these functional abnormalities
      in the cerebral cortex contribute to the memory impairment. Hippocampal glucose
      metabolism did not differ between the groups. Thus, the evidence did not support
      the hypothesis that parallel brain dysfunctions are responsible for the similar
      amnesic symptomatology after hippocampal and diencephalic damage. We hypothesize
      that the amnesic dysfunction of Korsakoff's syndrome depends on a disruption of
      thalamocortical interactions that mediate a function critical for normal memory
      storage. 

PMID- 23962018
TI  - Prevalence and patterns of multimorbidity among tuberculosis patients in Brazil:
      a cross-sectional study.
AB  - INTRODUCTION: The number of subjects with tuberculosis (TB) presenting with co
      occurrence of multiple chronic medical conditions, or multimorbidity (MM) is
      increasing in Brazil. This manuscript aimed to characterize subjects with TB,
      according to their MM status and to analyse factors associated with TB treatment
      outcomes. METHODS: This is a cross-sectional study that included 39,881 TB
      subjects reported in Brazil, in 2011. MM were defined as any (two or more)
      occurrence of chronic medical conditions in a TB patient (TB-MM). Data analysis
      was performed by hierarchical logistic regression models comparing TBMM with
      those with only TB. RESULTS: Of the reported TB cases in 2011, 454 (1.14%) had
      MM. The subjects in the age group 40-59 years (OR: 17.89; 95% CI, 5.71-56.03) and
      those >= 60 years (OR: 44.11; 95% CI, 14.09-138.06) were more likely to develop
      TB-MM. The TB-MM subjects were less likely to be male (OR: 0.63; 95% CI, 0.52
      0.76), institutionalized (OR: 0.59; 95% CI, 0.23-0.80) and live in rural areas
      (OR: 0.63; 95% CI, 0.42-0.95). Death from causes other than TB was higher among
      TB-MM subjects (OR: 1.76; 95% CI, 1.36-2.28). Of 454 TB-MM subjects 302 (66.5%)
      were cured and 152 (33.5%) were not cured. The odds of not being cured was 1.55
      (95% CI, 1.04-2.32) among males, 2.85 (95% CI, 1.12-7.28) among institutionalized
      subjects, and 3.93 (IC 95%, 1.86-8.30) among those who were infected with HIV. TB
      retreatment after previous abandonment (OR: 7.53; 95% CI, 2.58-21.97) and
      transfer from a treatment site (OR: 2.76; 95% CI, 1.20-6.38) were higher for
      subjects not cured compared to those who were cured. CONCLUSIONS: While TB is
      well recognized to be a disease engendered by social inequity, we found that even
      among TB patients, those who have MM have greater inequity in terms of
      socioeconomic status and adverse clinical outcomes. Addressing the problem of TB
      and TB-MM requires a multisectorial approach that includes health and social
      service organizations.

PMID- 23962020
TI  - Meta-analysis methods for risk differences.
AB  - The difference between two proportions, referred to as a risk difference, is a
      useful measure of effect size in studies where the response variable is
      dichotomous. Confidence interval methods based on a varying coefficient model are
      proposed for combining and comparing risk differences from multi-study between
      subjects or within-subjects designs. The proposed methods are new alternatives to
      the popular constant coefficient and random coefficient methods. The proposed
      varying coefficient methods do not require the constant coefficient assumption of
      effect size homogeneity, nor do they require the random coefficient assumption
      that the risk differences from the selected studies represent a random sample
      from a normally distributed superpopulation of risk differences. The proposed
      varying coefficient methods are shown to have excellent finite-sample performance
      characteristics under realistic conditions. 

PMID- 23962019
TI  - Human and avian extraintestinal pathogenic Escherichia coli: infections, zoonotic
      risks, and antibiotic resistance trends.
AB  - Extraintestinal pathogenic Escherichia coli (ExPEC) constitutes ongoing health
      concerns for women, newborns, elderly, and immunocompromised individuals due to
      increased numbers of urinary tract infections (UTIs), newborn meningitis,
      abdominal sepsis, and septicemia. E. coli remains the leading cause of UTIs, with
      recent investigations reporting the emergence of E. coli as the predominant cause
      of nosocomial and neonatal sepsis infections. This shift from the traditional
      Gram-positive bacterial causes of nosocomial and neonatal sepsis infections could
      be attributed to the use of intrapartum chemoprophylaxis against Gram-positive
      bacteria and the appearance of antibiotic (ATB) resistance in E. coli. While
      ExPEC strains cause significant healthcare concerns, these bacteria also infect
      chickens and cause the poultry industry economic losses due to costs of
      containment, mortality, and disposal of carcasses. To circumvent ExPEC-related
      costs, ATBs are commonly used in the poultry industry to prevent/treat microbial
      infections and promote growth and performance. In an unfortunate linkage, chicken
      products are suspected to be a source of foodborne ExPEC infections and ATB
      resistance in humans. Therefore, the emergence of multidrug resistance (MDR)
      (resistance to three or more classes of antimicrobial agents) among avian E. coli
      has created major economic and health concerns, affecting both human healthcare
      and poultry industries. Increased numbers of immunocompromised individuals,
      including the elderly, coupled with MDR among ExPEC strains, will continue to
      challenge the treatment of ExPEC infections and likely lead to increased
      treatment costs. With ongoing complications due to emerging ATB resistance, novel
      treatment strategies are necessary to control ExPEC infections. Recognizing and
      treating the zoonotic risk posed by ExPEC would greatly enhance food safety and
      positively impact human health.

PMID- 23962021
TI  - Protective mechanism of anethole on hepatic ischemia/reperfusion injury in mice.
AB  - The aim of this study was to investigate the hepatoprotective effect of anethole
      (trans-anethole, 1), a major component of Foeniculum vulgare, and its molecular
      mechanism during ischemia/reperfusion (I/R). Mice were subjected to 60 min of
      partial hepatic ischemia followed by 1 and 6 h of reperfusion. Compound 1 (50,
      100, and 200 mg/kg) or the vehicle alone (10% Tween 80-saline) was orally
      administered 1 h prior to ischemia. After 1 and 6 h of reperfusion, serum alanine
      aminotransferase, tumor necrosis factor-alpha, and interleukin 6 levels
      significantly increased, but these increases were attenuated by 1. Nuclear
      translocation of interferon regulatory factor (IRF)-1, release of high mobility
      group box (HMGB) 1 into the extracellular milieu, and the interactions between
      IRF-1 and histone acetyltransferase p300 increased after I/R. These increases
      were attenuated by 1. Compound 1 suppressed increases in toll-like receptor (TLR)
      4, myeloid differentiation primary response gene 88 protein expression,
      phosphorylation of p38, extracellular signal-regulated kinase, c-Jun N-terminal
      kinase, nuclear translocation of nuclear factor kappa B, and phosphorylated c
      Jun. The present findings suggest that 1 protects against hepatic I/R injury by
      suppression of IRF-1-mediated HMGB1 release and subsequent TLR activation. 

PMID- 23962022
TI  - Structural insights into the extra cellular segment of integrinbeta5 and
      molecular interaction studies.
AB  - Primary tumor cells often spread to other organs by metastasis. Despite of it,
      primary tumor cells break their surrounding extra cellular matrix (ECM) proteins
      and reach the destination organ by the process of intravasation and
      extravasation. Metastasized tumor cells induce the process of angiogenesis, this
      highly regulated process involves several ECM proteins. However, integrins are
      primarily involved in the blood vessel growth and repair. Therefore, integrins
      are promising angiogenesis targets. Integrins are receptors on cell surface,
      involved in signal transduction and attachments in extra cellular matrix (ECM).
      IntegrinalphaVbeta3 and alphaVbeta5 are implicated in tumor angiogenesis,
      metastasis, inflammation and bone resorption. The crystal structure of
      integrinalphavbeta5 is not available in protein structural databases, therefore;
      molecular model of integrinbeta5 structure was prepared and stereo chemical model
      quality was checked. Integrin beta5 active sites were identified based on
      insilico analysis tools. Further, molecular level interactions between
      integrinbeta5 and ECM proteins were predicted. In the present study ECM proteins
      such as focal adhesion kinase 1 (FAK1), annexin A5 and P21 activated kinase 4
      (PAK4) were considered for protein-protein docking, to understand inter molecular
      interactions. The predicted model is conceived to be stereo chemically good and
      can be used for molecular interaction studies of angiogenic inhibitors.

PMID- 23962023
TI  - Ribonucleases as a host-defence family: evidence of evolutionarily conserved
      antimicrobial activity at the N-terminus.
AB  - Vertebrate secreted RNases (ribonucleases) are small proteins that play important
      roles in RNA metabolism, angiogenesis or host defence. In the present study we
      describe the antimicrobial properties of the N-terminal domain of the hcRNases
      (human canonical RNases) and show that their antimicrobial activity is well
      conserved among their lineage. Furthermore, all domains display a similar
      antimicrobial mechanism, characterized by bacteria agglutination followed by
      membrane permeabilization. The results of the present study show that, for all
      antimicrobial hcRNases, (i) activity is retained at the N-terminus and (ii) the
      antimicrobial mechanism is conserved. Moreover, using computational analysis we
      show that antimicrobial propensity may be conserved at the N-terminus for all
      vertebrate RNases, thereby suggesting that a defence mechanism could be a primary
      function in vertebrate RNases and that the N-terminus was selected to ensure this
      property. In a broader context, from the overall comparison of the peptides'
      physicochemical and biological properties, general correlation rules could be
      drawn to assist in the structure-based development of antimicrobial agents. 

PMID- 23962024
TI  - Evaluation of seven DNA barcodes for differentiating closely related medicinal
      Gentiana species and their adulterants.
AB  - BACKGROUND: Species identification of living organisms by standard DNA sequences
      has been well-accepted. Consortium for the Barcode of Life (CBOL) recommends
      chloroplast regions rbcL and matK as the DNA barcodes for the land plants. This
      study aims to evaluate the feasibility and limitations of rbcL, matK, and 5 other
      commonly used regions as the DNA barcodes for the medicinal Gentiana and their
      adulterants, Gentiana. rhodantha and Podophyllum hexandrum. METHODS: The species
      differentiation power of rbcL, matK, nuclear internal transcribed spacer (ITS)
      and 5S rRNA intergenic spacer, and chloroplast trnH-psbA, trnL-F and rpl36-rps8
      intergenic spacers were tested in different medicinal Gentiana, including
      Gentiana scabra, Gentiana triflora, Gentiana manshurica and Gentiana rigescens,
      from common adulterants such as Gentiana rhodantha and Podophyllum hexandrum (a
      toxic herb producing podophyllotoxin). RESULTS: All seven tested loci could be
      used to differentiate medicinal Gentiana species from their adulterants, and to
      distinguish Guanlongdan from Jianlongdan. In terms of general differentiation
      powers, rbcL and matK had no significant advantages over the other five loci.
      Only the 5S rRNA and trnL-F intergenic spacers were able to discriminate the
      closely related species G. triflora, G. scabra and G. manshurica. CONCLUSION: The
      DNA barcodes rbcL and matK are useful in differentiation of closely related
      medicinal species of Gentiana, but had no significant advantages over the other
      five tested loci.

PMID- 23962025
TI  - Fabrication of bifunctional core-shell Fe3O4 particles coated with ultrathin
      phosphor layer.
AB  - Bifunctional monodispersed Fe3O4 particles coated with an ultrathin Y2O3:Tb3+
      shell layer were fabricated using a facile urea-based homogeneous precipitation
      method. The obtained composite particles were characterized by powder X-ray
      diffraction, transmission electron microscopy (TEM), quantum design vibrating
      sample magnetometry, and photoluminescence (PL) spectroscopy. TEM revealed
      uniform spherical core-shell-structured composites ranging in size from 306 to
      330 nm with a shell thickness of approximately 25 nm. PL spectroscopy confirmed
      that the synthesized composites displayed a strong eye-visible green light
      emission. Magnetic measurements indicated that the composite particles obtained
      also exhibited strong superparamagnetic behavior at room temperature. Therefore,
      the inner Fe3O4 core and outer Y2O3:Tb3+ shell layer endow the composites with
      both robust magnetic properties and strong eye-visible luminescent properties.
      These composite materials have potential use in magnetic targeting and
      bioseparation, simultaneously coupled with luminescent imaging. 

PMID- 23962026
TI  - Clinical review of obstructive primary cardiac tumors in childhood.
AB  - OBJECTIVES: This study aims to examine the long-term outcomes of conservative
      management compared with surgical resection for obstructive and nonobstructive
      primary cardiac tumors in children. DESIGN: A 20-year retrospective review of
      primary cardiac tumors seen in the right ventricular outflow tract (RVOT) and
      left ventricular outflow tract (LVOT) in children at The Hospital for Sick
      Children, Toronto, Canada. Student's t-tests and Fisher's exact chi-square were
      used to compare outcomes between the conservatively managed vs. surgical
      resection groups and the obstructive vs. nonobstructive tumor groups. RESULTS:
      Between 1990 and 2010, we identified 130 children with intracardiac tumors among
      52 937 (2.5 per 1000 children, 95th confidence interval: 2.1-2.9 per 1000).
      Thirty-six children (28%) had at least one cardiac tumor in the RVOT (n = 13) or
      LVOT (n = 23). Of those, 14 children had peak outflow gradients of >20 mm Hg at
      the diagnostic echocardiogram (median age at diagnosis: 4 days, range 0 days-6
      months; mean follow-up: 7.8 +/- 4.5 years). Rhabdomyoma was the most common tumor
      27/36 (75%). Twelve (33%) patients underwent surgical repair vs. 24 patients who
      were observed only. There was no difference in survival. Patients who had surgery
      tended to be sicker (intubated at diagnosis 4/12, 33% vs. 1/23, 4%, P = .04).
      There were no deaths in either group. One child required reoperation for severe
      aortic insufficiency, and only one child in the observation group had residual
      obstruction at most recent follow-up. CONCLUSIONS: Primary cardiac tumors in
      childhood obstructing the RVOT or LVOT are uncommon findings after birth and may
      be managed nonsurgically in most cases.

PMID- 23962027
TI  - Body mass index and metabolic factors predict glomerular filtration rate and
      albuminuria over 20 years in a high-risk population.
AB  - BACKGROUND: The number of individuals suffering from chronic kidney disease (CKD)
      is increasing. Therefore, early identification of modifiable predictors of CKD is
      highly desirable. Previous studies suggest an association between body mass index
      (BMI), metabolic factors and CKD. METHODS: Data of 241 high risk patients with
      information on renal function and albuminuria from the Renal Disease in
      Vorarlberg (RENVOR) study (2010-2011) were linked with long-term measurements of
      metabolic factors in the same patients from the population-based Vorarlberg
      Health Monitoring & Prevention Program (VHM&PP) cohort study (1988-2005). Actual
      estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio
      (ACR) were determined. BMI, blood pressure, fasting glucose, total cholesterol,
      triglycerides and Gamma-glutamyltransferase (GGT) were available from previous
      health examinations performed up to 25 years ago. Linear regression models were
      applied to identify predictors of current renal function. RESULTS: At all-time
      points BMI was significantly inversely associated with actual eGFR and positively
      with actual albuminuria in men, but not in women. Serum GGT and triglycerides
      were significantly positively associated with albuminuria in men at all-time
      points. Fasting glucose levels more than 20 years earlier were associated with
      increased albuminuria in women and reduced eGFR in men, whereas at later time
      points it was associated with albuminuria in men. CONCLUSIONS: BMI, serum GGT,
      and triglycerides are long-term predictors of renal function in men. In women
      however, anthropometric and metabolic parameters seem to be less predictive of
      eGFR and albuminuria.

PMID- 23962028
TI  - Health-related quality of life and disease symptoms in postmenopausal women with
      HR(+), HER2(-) advanced breast cancer treated with everolimus plus exemestane
      versus exemestane monotherapy.
AB  - OBJECTIVE: Everolimus (EVE)+exemestane (EXE; n = 485) more than doubled median
      progression-free survival versus placebo (PBO) + EXE (n = 239), with a manageable
      safety profile and no deterioration in health-related quality-of-life (HRQOL) in
      patients with hormone-receptor-positive (HR(+)) advanced breast cancer (ABC) who
      recurred or progressed on/after nonsteroidal aromatase inhibitor (NSAI) therapy.
      To further evaluate EVE + EXE impact on disease burden, we conducted additional
      post-hoc analyses of patient-reported HRQOL. RESEARCH DESIGN AND METHODS: HRQOL
      was assessed using EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline and
      every 6 weeks thereafter until treatment discontinuation because of disease
      progression, toxicity, or consent withdrawal. Endpoints included the QLQ-C30
      Global Health Status (QL2) scale, the QLQ-BR23 breast symptom (BRBS), and arm
      symptom (BRAS) scales. Between-group differences in change from baseline were
      assessed using linear mixed models with selected covariates. Sensitivity analysis
      using pattern-mixture models determined the effect of study discontinuation
      on/before week 24. Treatment arms were compared using differences of least
      squares mean (LSM) changes from baseline and 95% confidence intervals (CIs) at
      each timepoint and overall. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov:
      NCT00863655. MAIN OUTCOME MEASURES: Progression-free survival, survival, response
      rate, safety, and HRQOL. RESULTS: Linear mixed models (primary model)
      demonstrated no statistically significant overall difference between EVE + EXE
      and PBO + EXE for QL2 (LSM difference = -1.91; 95% CI = -4.61, 0.78), BRBS (LSM
      difference = -0.18; 95% CI = -1.98, 1.62), or BRAS (LSM difference = -0.42; 95%
      CI = -2.94, 2.10). Based on pattern-mixture models, patients who dropped out
      early had worse QL2 decline on both treatments. In the expanded pattern-mixture
      model, EVE + EXE-treated patients who did not drop out early had stable BRBS and
      BRAS relative to PBO + EXE. KEY LIMITATIONS: HRQOL data were not collected after
      disease progression. CONCLUSIONS: These analyses confirm that EVE + EXE provides
      clinical benefit without adversely impacting HRQOL in patients with HR(+) ABC who
      recurred/progressed on prior NSAIs versus endocrine therapy alone.

PMID- 23962029
TI  - Thromboelastometric detection of clotting Factor XIII deficiency in cardiac
      surgery patients.
AB  - AIM(S): In this article, we aimed to investigate plasma Factor XIII levels after
      extracorporeal circulation in cardiac surgery by thromboelastometric detection,
      as extracorporeal circulation causes various coagulation disorders due to the
      exposure of blood to artificial surfaces, inflammatory induction and mechanical
      destruction of platelets and coagulation factors, which may particularly affect
      factors with long half-lives, such as Factor XIII. BACKGROUND: Since transfusion
      algorithms are often empirical and laboratory analysis of Factor XIII plasma
      levels may not be available 24 h a day, bed-side testing using rotational
      thromboelastometry (ROTEM) could offer a splendid option to define the cause of
      excessive peri-operative bleeding disorders in general and Factor XIII levels in
      particular in a timely manner and thus facilitating exact substitution therapy.
      METHODS: In this trial, we investigated 25 cardiac surgery patients with
      extracorporeal bypass times over 100 min. Standard laboratory and ROTEM analyses
      were performed post-operatively at the time of intensive care unit admission and
      6 h later. We implemented EXTEM with additional Factor XIII (teenTEM) as
      additional test by adding 0.625 IU Factor XIII to standard EXTEM reagents.
      RESULTS: In this observational study, we could not demonstrate a correlation
      between Factor XIII and MCFEXTEM , CFTEXTEM or MLEXTEM . Neither Factor XIII
      plasma levels nor MCFEXTEM could predict blood loss. In accordance with previous
      findings, we were able to demonstrate increased maximum clot firmness (MCF),
      decreased clot formation time and decreased maximum lysis by adding Factor XIII
      in vitro (teenTEM vs EXTEM) indicating an improvement in the coagulation process.
      As shown before, we also found a strong correlation between MCF and platelet and
      fibrinogen plasma levels. CONCLUSION: In summary, 'teenTEM' test does not seem to
      detect Factor XIII deficient patients in cardiac surgery. Furthermore, post
      operative blood loss could not be predicted neither by ROTEM nor by laboratory
      analysis of Factor XIII. In vitro administration of Factor XIII appears to
      improve laboratory measures of haemostasis.

PMID- 23962030
TI  - Species differences in intestinal glucuronidation activities between humans,
      rats, dogs and monkeys.
AB  - 1.  Glucuronidation via UDP-glucuronosyltransferase (UGT) in the intestine has
      been reported to influence the pharmacokinetics (PK) of drugs; however,
      information concerning the differences in activity between species is limited.
      Here, we investigated the in vitro and in vivo activities of intestinal
      glucuronidation for 17 UGT substrates in humans, rats, dogs and monkeys. 2. 
      Although in vitro intrinsic clearance (CLint,u,UGT) in intestinal microsomes
      showed a good correlation between humans and laboratory animals, values tended to
      be lower in humans than in laboratory animals. The ratio of CLint,u,UGT in the
      absence and presence of bovine serum albumin differed between species. In vivo,
      the fraction of drug absorbed (FaFg) in humans correlated with that in dogs and
      monkeys, but not in rats. 3.  While an inverse correlation between CLint,u,UGT
      and FaFg was observed in each species, the CLint,u,UGT values in the intestinal
      microsomes corresponding to FaFg values in dogs were three to four times higher
      than in other animals. 4.  These results indicate the need for a degree of
      caution when extrapolating PK data from laboratory animals to humans.

PMID- 23962032
TI  - Mechanical ventilation triggers hippocampal apoptosis by vagal and dopaminergic
      pathways.
AB  - RATIONALE: Critically ill patients frequently develop neuropsychological
      disturbances including acute delirium or memory impairment. The need for
      mechanical ventilation is a risk factor for these adverse events, but a mechanism
      that links lung stretch and brain injury has not been identified. OBJECTIVES: To
      identify the mechanisms that lead to brain dysfunction during mechanical
      ventilation. METHODS: Brains from mechanically ventilated mice were harvested,
      and signals of apoptosis and alterations in the Akt survival pathway were
      studied. These measurements were repeated in vagotomized or haloperidol-treated
      mice, and in animals intracerebroventricularly injected with selective dopamine
      receptor blockers. Hippocampal slices were cultured and treated with micromolar
      concentrations of dopamine, with or without dopamine receptor blockers. Last,
      levels of dysbindin, a regulator of the membrane availability of dopamine
      receptors, were assessed in the experimental model and in brain samples from
      ventilated patients. MEASUREMENTS AND MAIN RESULTS: Mechanical ventilation
      triggers hippocampal apoptosis as a result of type 2 dopamine receptor activation
      in response to vagal signaling. Activation of these receptors blocks the
      Akt/GSK3beta prosurvival pathway and activates the apoptotic cascade, as
      demonstrated in vivo and in vitro. Vagotomy, systemic haloperidol, or
      intracerebroventricular raclopride (a type 2 dopamine receptor blocker)
      ameliorated this effect. Moreover, ventilation induced a concomitant change in
      the expression of dysbindin-1C. These results were confirmed in brain samples
      from ventilated patients. CONCLUSIONS: These results prove the existence of a
      pathogenic mechanism of lung stretch-induced hippocampal apoptosis that could
      explain the neurological changes in ventilated patients and may help to identify
      novel therapeutic approaches.

PMID- 23962033
TI  - Effect of detergents on the physicochemical properties of skin stratum corneum: a
      two-photon excitation fluorescence microscopy study.
AB  - OBJECTIVE: Understanding the structural and dynamical features of skin is
      critical for advancing innovation in personal care and drug discovery. Synthetic
      detergent mixtures used in commercially available body wash products are thought
      to be less aggressive towards the skin barrier when compared to conventional
      detergents. The aim of this work is to comparatively characterize the effect of a
      mild synthetic cleanser mixture (SCM) and sodium dodecyl sulphate (SDS) on the
      hydration state of the intercellular lipid matrix and on proton activity of
      excised skin stratum corneum (SC). METHOD: Experiments were performed using two
      photon excitation fluorescence microscopy. Fluorescent images of fluorescence
      reporters sensitive to proton activity and hydration of SC were obtained in
      excised skin and examined in the presence and absence of SCM and SDS detergents.
      RESULTS: Hydration of the intercellular lipid matrix to a depth of 10 MUm into
      the SC was increased upon treatment with SCM, whereas SDS shows this effect only
      at the very surface of SC. The proton activity of SC remained unaffected by
      treatment with either detergent. CONCLUSION: While our study indicates that the
      SC is very resistant to external stimuli, it also shows that, in contrast to the
      response to SDS, SCM to some extent modulates the in-depth hydration properties
      of the intercellular lipid matrix within excised skin SC.

PMID- 23962034
TI  - An autoimmune disease refractory to immunosuppressive regimens: celiac disease
      diagnosed long after liver transplantation.
AB  - CD is defined as T-lymphocyte-mediated gluten sensitivity. Although CD is known
      to affect the small intestine, it is nonetheless a multisystem disorder. Liver
      involvement in CD may vary from isolated hypertransaminasemia to cirrhosis.
      Because CD is an inappropriate immune response to gluten proteins, strict gluten
      free diet is the principal therapy, along with management of liver dysfunction.
      In patients who fail to respond to a gluten-free diet, immunosuppressive drugs
      may improve intestinal inflammatory activity in untreated CD. The present case
      report is of a 25-yr-old woman with diarrhea lasting several weeks. The patient
      had received a liver transplant 13 yr earlier, and presented with cryptogenic
      cirrhosis diagnosed as CD. This appears to be the first case of its kind in which
      a pediatric long-term liver transplant patient presents with diarrhea eventually
      diagnosed as CD whose diet included gluten, and who was treated by an
      immunosuppressive drug regimen. Because of the normalization of CD-related
      antibodies in the post-transplantation period without gluten restriction, CD
      should be part of a list of diagnostic possibilities in liver transplant patients
      presenting with diarrhea of unknown etiology. 

PMID- 23962035
TI  - Two-year results of photodynamic therapy with or without intravitreal ranibizumab
      for polypoidal choroidal vasculopathy.
AB  - PURPOSE: To compare the 2-year outcomes of photodynamic therapy (PDT) with or
      without intravitreal ranibizumab (IVR) for polypoidal choroidal vasculopathy
      (PCV). METHODS: Medical charts from 58 patients with PCV, who had been followed
      up for more than 2 years after initial treatment, were reviewed retrospectively.
      Visual outcomes were compared between 2 groups, consisting of 34 patients treated
      with PDT monotherapy without IVR and 24 with the combination of PDT and IVR, and
      the factors associated with the 2-year visual outcomes were investigated using
      multiple regression analysis. RESULTS: In the PDT monotherapy group, the
      logarithm of the minimum angle of resolution (logMAR) of the best-corrected
      visual acuity (BCVA) improved significantly at 12 months (P=0.026), but was not
      significantly different from the initial logMAR BCVA at 24 months (P=0.21). By
      contrast, the logMAR BCVA improved significantly at 12 months and was maintained
      throughout the second 12-month period (P<0.001 at all time points) in the
      combined PDT group. Multiple regression analysis revealed that the initial BCVA
      (P<0.001), the greatest linear dimension of the initial PDT (P=0.006), and the
      combined PDT (P=0.039) were predictors of visual outcomes at 24 months.
      CONCLUSIONS: Combined PDT with IVR is a better treatment modality compared with
      PDT monotherapy, and results in improvement of visual outcomes at 24 months after
      the initial treatment.

PMID- 23962031
TI  - Prehospital use of cervical collars in trauma patients: a critical review.
AB  - The cervical collar has been routinely used for trauma patients for more than 30
      years and is a hallmark of state-of-the-art prehospital trauma care. However, the
      existing evidence for this practice is limited: Randomized, controlled trials are
      largely missing, and there are uncertain effects on mortality, neurological
      injury, and spinal stability. Even more concerning, there is a growing body of
      evidence and opinion against the use of collars. It has been argued that collars
      cause more harm than good, and that we should simply stop using them. In this
      critical review, we discuss the pros and cons of collar use in trauma patients
      and reflect on how we can move our clinical practice forward. Conclusively, we
      propose a safe, effective strategy for prehospital spinal immobilization that
      does not include routine use of collars.

PMID- 23962037
TI  - Accelerated formation of metal oxide thin film at 200  degrees C using oxygen
      supplied by a nitric acid additive and residual organic suction vacuum annealing
      for thin-film transistor applications.
AB  - Oxide semiconductors have gradually replaced amorphous and polycrystalline
      silicon for thin-film transistor (TFT) because of their high mobility and large
      area uniformity. Especially, the oxide semiconductors have also achieved the low
      cost manufacturing using a solution process. However, because the solution
      processed oxide semiconductors require a high thermal energy to form the oxide
      thin film, the additional solution synthesis and annealing process are needed for
      low-temperature solution process. Because the conventional solution-processed
      oxide thin films have low oxidation level and high residual organic concentration
      at low annealing temperature, we propose the novel solution process that includes
      the nitric acid additive and the vacuum ambient annealing as an oxidizing agent
      and a residual organic suction, respectively. Therefore, we have successfully
      developed the simple oxide solution process and the soluble InZnO TFT with high
      field-effect mobility of 3.38 cm(2)/(V s) at 200  degrees C. 

PMID- 23962036
TI  - Residential movement patterns of families of young children with chronic
      conditions in Ontario, Canada: a population-based cohort study.
AB  - INTRODUCTION: Care giving for children with chronic diseases can lead to
      financial strain and compromised family well being. Little is known about whether
      these stresses lead to changes in residential movement patterns as they relate to
      income adequacy and proximity to care. METHODS: We compared the residential
      movement patterns and associated changes in neighbourhood income of children with
      mild to severe chronic diseases compared with those that are healthy. A cohort of
      infants born from 2002-2007 in Ontario, Canada was followed for 5 years and
      divided into those with single- or multiple- body system complex chronic
      conditions (CCCs); low birth weight (LBW); asthma/recurrent wheeze (A/RW) and the
      control group of otherwise healthy children. RESULTS: Of 598,716 children
      studied, 15,207 had a single CCC, 3,600 multiple CCCs, 33,206 LBW, 57,137 A/RW
      and 489,566 were healthy. Lowest income quintile children were most likely to
      move residence. Compared with healthy controls, chronic disease cohorts, apart
      from those with asthma, were more likely to be born in the lowest income quintile
      neighbourhood and to move. Among children who moved, all chronic disease cohorts
      were significantly more likely to move to a low income quintile neighborhood
      (adjusted odds ratios for all chronic disease cohorts of 1.1-1.2). There were no
      differences across cohorts in residential movement close to a children's
      hospital. CONCLUSIONS: Young children with chronic conditions, particularly those
      born in low income neighbourhoods, are more likely to move residence than other
      healthy young children. However, it does not seem that proximity to specialized
      care is driving this movement. Further research is required to determine if these
      movement patterns impact the ability of children with chronic conditions to
      secure health services.

PMID- 23962038
TI  - Nitric oxide and reactive oxygen species in limb vascular function: what is the
      effect of physical activity?
AB  - Nitric oxide (NO) is known to be one of the most important regulatory compounds
      within the cardiovascular system where it is central for functions such as
      regulation of blood pressure, blood flow, and vascular growth. The
      bioavailability of NO is determined by a balance between, on one hand, the extent
      of enzymatic and non-enzymatic formation of NO and on the other hand, removal of
      NO, which in part is dependent on the reaction of NO with reactive oxygen species
      (ROS). The presence of ROS is dependent on the extent of ROS formation via
      mitochondria and/or enzymes such as NAD(P)H oxidase (NOX) and xanthine oxidase
      (XO) and the degree of ROS removal through the antioxidant defense system or
      other reactions. The development of cardiovascular disease has been proposed to
      be closely related to a reduced bioavailability of NO in parallel with an
      increased presence of ROS. Excessive levels of ROS not only lower the
      bioavailability of NO but may also cause cellular damage in the cardiovascular
      system. Physical activity has been shown to greatly improve cardiovascular
      function, in part through improved bioavailability of NO, enhanced endogenous
      antioxidant defense and a lowering of the expression of ROS-forming enzymes.
      Regular physical activity is therefore likely to be a highly useful tool in the
      treatment of cardiovascular disease. Future studies should focus on which form of
      exercise may be most optimal for enhancing NO bioavailability and improving
      cardiovascular health.

PMID- 23962039
TI  - Sister chromatid cohesion defects are associated with chromosome instability in
      Hodgkin lymphoma cells.
AB  - BACKGROUND: Chromosome instability manifests as an abnormal chromosome complement
      and is a pathogenic event in cancer. Although a correlation between abnormal
      chromosome numbers and cancer exist, the underlying mechanisms that cause
      chromosome instability are poorly understood. Recent data suggests that aberrant
      sister chromatid cohesion causes chromosome instability and thus contributes to
      the development of cancer. Cohesion normally functions by tethering nascently
      synthesized chromatids together to prevent premature segregation and thus
      chromosome instability. Although the prevalence of aberrant cohesion has been
      reported for some solid tumors, its prevalence within liquid tumors is unknown.
      Consequently, the current study was undertaken to evaluate aberrant cohesion
      within Hodgkin lymphoma, a lymphoid malignancy that frequently exhibits
      chromosome instability. METHODS: Using established cytogenetic techniques, the
      prevalence of chromosome instability and aberrant cohesion was examined within
      mitotic spreads generated from five commonly employed Hodgkin lymphoma cell lines
      (L-1236, KM-H2, L-428, L-540 and HDLM-2) and a lymphocyte control. Indirect
      immunofluorescence and Western blot analyses were performed to evaluate the
      localization and expression of six critical proteins involved in the regulation
      of sister chromatid cohesion. RESULTS: We first confirmed that all five Hodgkin
      lymphoma cell lines exhibited chromosome instability relative to the lymphocyte
      control. We then determined that each Hodgkin lymphoma cell line exhibited
      cohesion defects that were subsequently classified into mild, moderate or severe
      categories. Surprisingly, ~50% of the mitotic spreads generated from L-540 and
      HDLM-2 harbored cohesion defects. To gain mechanistic insight into the underlying
      cause of the aberrant cohesion we examined the localization and expression of six
      critical proteins involved in cohesion. Although all proteins produced the
      expected nuclear localization pattern, striking differences in RAD21 expression
      was observed: RAD21 expression was lowest in L-540 and highest within HDLM-2.
      CONCLUSION: We conclude that aberrant cohesion is a common feature of all five
      Hodgkin lymphoma cell lines evaluated. We further conclude that aberrant RAD21
      expression is a strong candidate to underlie aberrant cohesion, chromosome
      instability and contribute to the development of the disease. Our findings
      support a growing body of evidence suggesting that cohesion defects and aberrant
      RAD21 expression are pathogenic events that contribute to tumor development.

PMID- 23962040
TI  - Profile of maternal CD4 T-cell effector function during normal pregnancy and in
      women with a history of recurrent miscarriage.
AB  - The traditional paradigm suggests that during normal pregnancy maternal
      immunological tolerance of the allogenic fetus is association with a maternal T
      lymphocyte shift from a Th1 to a Th2 phenotype, with the opposite effect reported
      in patients with recurrent miscarriage. However, studies on maternal peripheral
      blood are conflicting. In the present study, we characterized the maternal CD4 T
      cell effector subsets, including the recently described Th17 subset, during
      normal pregnancy (cross-sectional cohort, n=71; longitudinal cohort, n=17) and
      contrasted this with women with recurrent miscarriage (n=24). Longitudinal
      analysis of peripheral blood from normal pregnancy demonstrated a fall in the
      percentage of Th17 cells between the first and second trimester (P<=0.05), but no
      significant changes were observed across gestation or the post-natal period in
      Th1 or Th2 subsets. In contrast, in women with a history of recurrent
      miscarriage, an elevated proportion of Th17 (0.314% compared with 0.097%;
      P=0.0009) and Th1 (12.4% compared with 5.3%; P=0.0002) cells was detected. The
      suggestion that Th17 cells may have a role in the normal events of implantation
      and early pregnancy requires further evaluation and mechanistic studies. The
      results of the present study, by conducting a careful longitudinal analysis,
      demonstrate that a peripheral Th1/Th2 shift is not a requirement for normal
      pregnancy. By contrast, the profound increase in Th1 and Th17 cells in women with
      recurrent miscarriage indicates that peripheral immunological dysfunction may be
      important in this group specifically, and these assays may be important in
      guiding therapeutic interventions in this group and warrant further investigation
      to determine whether they are predictive of outcome or responses to
      immunomodulatory therapy. 

PMID- 23962041
TI  - Endocrine manifestations and management of Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is a complex genetic disorder, caused by lack of
      expression of genes on the paternally inherited chromosome 15q11.2-q13. In
      infancy it is characterized by hypotonia with poor suck resulting in failure to
      thrive. As the child ages, other manifestations such as developmental delay,
      cognitive disability, and behavior problems become evident. Hypothalamic
      dysfunction has been implicated in many manifestations of this syndrome including
      hyperphagia, temperature instability, high pain threshold, sleep disordered
      breathing, and multiple endocrine abnormalities. These include growth hormone
      deficiency, central adrenal insufficiency, hypogonadism, hypothyroidism, and
      complications of obesity such as type 2 diabetes mellitus. This review summarizes
      the recent literature investigating optimal screening and treatment of endocrine
      abnormalities associated with PWS, and provides an update on nutrition and food
      related behavioral intervention. The standard of care regarding growth hormone
      therapy and surveillance for potential side effects, the potential for central
      adrenal insufficiency, evaluation for and treatment of hypogonadism in males and
      females, and the prevalence and screening recommendations for hypothyroidism and
      diabetes are covered in detail. PWS is a genetic syndrome in which early
      diagnosis and careful attention to detail regarding all the potential endocrine
      and behavioral manifestations can lead to a significant improvement in health and
      developmental outcomes. Thus, the important role of the provider caring for the
      child with PWS cannot be overstated. 

PMID- 23962042
TI  - Sertraline inhibits the transport of PAT1 substrates in vivo and in vitro.
AB  - BACKGROUND AND PURPOSE: Intestinal nutrient transporters may mediate the uptake
      of drugs. The aim of this study was to investigate whether sertraline interacts
      with the intestinal proton-coupled amino acid transporter 1 PAT1 (SLC36A1).
      EXPERIMENTAL APPROACH: In vitro investigations of interactions between sertraline
      and human (h)PAT1, hSGLT1 (sodium-glucose linked transporter 1) and hPepT1
      (proton-coupled di-/tri-peptide transporter 1) were conducted in Caco-2 cells
      using radiolabelled substrates. In vivo pharmacokinetic investigations were
      conducted in male Sprague-Dawley rats using gaboxadol (10 mg.kg(-1), p.o.) as a
      PAT1 substrate and sertraline (0-30.6 mg.kg(-1)). Gaboxadol was quantified by
      hydrophilic interaction chromatography followed by MS/MS detection. KEY RESULTS:
      Sertraline inhibited hPAT1-mediated L-[(3)H]-Pro uptake in Caco-2 cells. This
      interaction between sertraline and PAT1 appeared to be non-competitive. The
      uptake of the hSGLT1 substrate [(14)C]-alpha-methyl-D-glycopyranoside and the
      hPepT1 substrate [(14)C]-Gly-Sar in Caco-2 cells was also decreased in the
      presence of 0.3 mM sertraline. In rats, the administration of sertraline (0.1-10
      mM, corresponding to 0.3-30.6 mg.kg(-1), p.o.) significantly reduced the maximal
      gaboxadol plasma concentration and AUC after its administration p.o. CONCLUSIONS
      AND IMPLICATIONS: Sertraline is an apparent non-competitive inhibitor of hPAT1
      mediated transport in vitro. This inhibitory effect of sertraline is not specific
      to hPAT1 as substrate transport via hPepT1 and hSGLT1 was also reduced in the
      presence of sertraline. In vivo, sertraline reduced the amount of gaboxadol
      absorbed, suggesting that the inhibitory effect of sertraline on PAT1 occurs both
      in vitro and in vivo. Hence, sertraline could alter the bioavailability of drugs
      absorbed via PAT1.

PMID- 23962044
TI  - Abstracts of the Smart Strokes 2013 Conference. Risk, Recovery & Reorganisation
      9th Australasian Nursing & Allied Health Stroke Conference. August 22-23, 2013.
      Queensland, Australia.

PMID- 23962043
TI  - Core modular blood and brain biomarkers in social defeat mouse model for post
      traumatic stress disorder.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) is a severe anxiety disorder
      that affects a substantial portion of combat veterans and poses serious
      consequences to long-term health. Consequently, the identification of diagnostic
      and prognostic blood biomarkers for PTSD is of great interest. Previously, we
      assessed genome-wide gene expression of seven brain regions and whole blood in a
      social defeat mouse model subjected to various stress conditions. RESULTS: To
      extract biological insights from these data, we have applied a new computational
      framework for identifying gene modules that are activated in common across blood
      and various brain regions. Our results, in the form of modular gene networks that
      highlight spatial and temporal biological functions, provide a systems-level
      molecular description of response to social stress. Specifically, the common
      modules discovered between the brain and blood emphasizes molecular transporters
      in the blood-brain barrier, and the associated genes have significant overlaps
      with known blood signatures for PTSD, major depression, and bipolar disease.
      Similarly, the common modules specific to the brain highlight the components of
      the social defeat stress response (e.g., fear conditioning pathways) in each
      brain sub-region. CONCLUSIONS: Many of the brain-specific genes discovered are
      consistent with previous independent studies of PTSD or other mental illnesses.
      The results from this study further our understanding of the mechanism of stress
      response and contribute to a growing list of diagnostic biomarkers for PTSD.

PMID- 23962045
TI  - Hospital admissions for dental treatment among children with cleft lip and/or
      palate born between 1997 and 2003: an analysis of Hospital Episode Statistics in
      England.
AB  - BACKGROUND: Children with clefts have an increased tendency for dental anomalies
      and caries. AIM: To determine the pattern of hospital admissions for dental
      treatment during primary dentition among children with clefts. DESIGN: Cohort
      study based on Hospital Episode Statistics, an administrative database of all
      admissions to National Health Service hospitals in England. Patients born alive
      between 1997 and 2003 who had both a cleft diagnosis and cleft repair were
      included. The number of hospital admissions for surgical removal of teeth, simple
      extraction of teeth, and restoration of teeth before the age of seven was
      examined. RESULTS: Eight hundred and fifty-eight hospital admissions for dental
      treatment among 6551 children (<7 year) with a cleft were identified. 66.4% of
      admissions were primarily for caries and 95.6% involved extractions. 11.4% of
      children had at least one admission for dental treatment. The presence of
      additional anomalies, having a more severe cleft type, and living in relatively
      deprived areas increased the risk of hospital admission. CONCLUSIONS: Factors
      increasing the risk of hospital admission among cleft children should be taken
      into account when planning services. Efforts to reduce the number of hospital
      admissions should be focused on disease prevention, particularly among those most
      at risk of caries.

PMID- 23962047
TI  - Gas gangrene caused by clostridium perfringens involving the liver, spleen, and
      heart in a man 20 years after an orthotopic liver transplant: a case report.
AB  - Despite advances in immunosuppression and liver transplant in the past, mortality
      and morbidity caused by infections remain major problems. We present a 71-year
      old man who was admitted to our internal intensive care unit with septicemia.
      Upon admission, he had poorly localized epigastric pain and fever of 2 days '
      duration. Twenty years earlier, he had undergone an orthotopic liver transplant.
      Testing revealed a high C-reactive protein level, elevated liver enzymes, and an
      acute kidney injury. A computer tomography scan showed 2 circular, non--rim
      enhancing, totally emphysematous intrahepatic lesions. Additionally, gas could be
      seen in the portal veins mainly, as well as in the biliary system, in the right
      auricle, and the splenic veins. To the best of our knowledge, he showed no
      malignant lesion or predisposing trauma. Empirically, treatment with broad
      spectrum antibiotics was begun, and the patient was transferred to the operating
      suite. When surgery began, blood cultures revealed the presence of gram-positive
      bacilli, which were identified as Clostridium perfringens. Seven hours after the
      surgery, the patient developed asystole and died. In septic patients presenting
      with severe hemolysis, Clostridium perfringens infection must be considered in
      the absence of a malignant lesion or a predisposing trauma; a previous episode of
      gastroenteritis might be a predisposing trauma by impairing the barrier of the
      intestinal flora, leading to Clostridium perfringens infection.

PMID- 23962046
TI  - Traumatic brain injury among older adults at level I and II trauma centers.
AB  - Individuals 65 years of age and over have the highest rates of traumatic brain
      injury (TBI)-related hospitalizations and deaths, and older adults (defined
      variably across studies) have particularly poor outcomes after TBI. The factors
      predicting these outcomes remain poorly understood, and age-specific care
      guidelines for TBI do not exist. This study provides an overview of TBI in older
      adults using data from the National Trauma Data Bank (NTDB) gathered between 2007
      and 2010, evaluates age group-specific trends in rates of TBI over time using
      U.S. Census data, and examines whether routinely collected information is able to
      predict hospital discharge status among older adults with TBI in the NTDB.
      Results showed a 20-25% increase in trauma center admissions for TBI among the
      oldest age groups (those >=75 years), relative to the general population, between
      2007 and 2010. Older adults (>=65 years) with TBI tended to be white females who
      have incurred an injury from a fall resulting in a "severe" Abbreviated Injury
      Scale (AIS) score of the head. Older adults had more in-hospital procedures, such
      as neuroimaging and neurosurgery, tended to experience longer hospital stays, and
      were more likely to require continued medical care than younger adults. Older
      age, injury severity, and hypotension increased the odds of in-hospital death.
      The public health burden of TBI among older adults will likely increase as the
      Baby Boom generation ages. Improved primary and secondary prevention of TBI in
      this cohort is needed.

PMID- 23962048
TI  - Structural and functional response of the soil bacterial community to application
      of manure from difloxacin-treated pigs.
AB  - Difloxacin (DIF) belongs to the class of fluoroquinolone antibiotics that have
      been intensively used for the treatment of bacterial infections in veterinary and
      human medicine. The aim of this field study was to compare the effect of manure
      from DIF-treated pigs and untreated pigs on the bacterial community structure and
      resistance gene abundance in bulk soil and rhizosphere of maize. A significant
      effect of DIF manure on the bacterial community composition in bulk soil was
      revealed by denaturing gradient gel electrophoresis (DGGE) of bacterial 16S rRNA
      gene fragments amplified from total community DNA. In few samples, quinolone
      resistance genes qnrB and qnrS1/qnrS2 were detected by PCR and subsequent
      hybridization, while qnrA was not detected. Quantitative PCR revealed an
      increased abundance of the integrase gene intI1 of class I integrons and
      sulfonamide resistance genes sul1 and sul2 in DIF manure-treated bulk soil and
      rhizosphere, relative to 16S rRNA genes, while traN genes specific for LowGC-type
      plasmids were increased only in bulk soil. Principal component analysis of DGGE
      profiles suggested a manure effect in soil until day 28, but samples of days 71
      and 140 were found close to untreated soil, indicating resilience of soil
      community compositions from disturbances by manure.

PMID- 23962049
TI  - Histamine stimulates hydrogen peroxide production by bronchial epithelial cells
      via histamine H1 receptor and dual oxidase.
AB  - Oxidative stress has been implicated in the pathogenesis of bronchial asthma.
      Besides granulocytes, the airway epithelium can produce large amounts of reactive
      oxygen species and can contribute to asthma-related oxidative stress. Histamine
      is a major inflammatory mediator present in large quantities in asthmatic
      airways. Whether histamine triggers epithelium-derived oxidative stress is
      unknown. We therefore aimed at characterizing human airway epithelial H2O2
      production stimulated by histamine. We found that air-liquid interface cultures
      of primary human bronchial epithelial cells (BECs) and an immortalized BEC model
      (Cdk4/hTERT HBEC) produce H2O2 in response to histamine. The main source of
      airway epithelial H2O2 is an NADPH dual oxidase, Duox1. Out of the four histamine
      receptors (H1R-H4R), H1R has the highest expression in BECs and mediates the H2O2
      producing effects of histamine. IL-4 induces Duox1 gene and protein expression
      levels and enhances histamine-induced H2O2 production by epithelial cells. Using
      HEK-293 cells expressing Duox1 or Duox2 and endogenous H1R, histamine triggers an
      immediate intracellular calcium signal and H2O2 release. Overexpression of H1R
      further increases the oxidative output of Duox-expressing HEK-293 cells. Our
      observations show that BECs respond to histamine with Duox-mediated H2O2
      production. These findings reveal a mechanism that could be an important
      contributor to oxidative stress characteristic of asthmatic airways, suggesting
      novel therapeutic targets for treating asthmatic airway disease. 

PMID- 23962050
TI  - Delayed short-term administration of granulocyte colony-stimulating factor is a
      good mobilization strategy for harvesting autologous peripheral blood stem cells
      in pediatric patients with solid tumors.
AB  - PBSCs have become the preferred source of autologous stem cells for supporting
      high-dose chemotherapy in childhood solid tumors. The aims of this retrospective
      study were to examine the optimal timing for administration of G-CSF after
      chemotherapy and to identify the patients from whom an optimal dose of PBSCs can
      be harvested. We evaluated the timing of G-CSF administration for harvesting
      PBSCs in patients with childhood solid tumors. G-CSF was administered immediately
      after chemotherapy in eight patients (11 harvests, long-term group) and following
      recovery from hematological nadirs in 17 patients (21 harvests, short-term
      group). The median duration of G-CSF administration was 22 vs. 5 days,
      respectively (p < 0.005), and the dose of harvested CD34(+) cells (*10(6) /kg)
      was 1.4 vs. 2.9, respectively (p = 0.023). Our results suggest that short-term G
      CSF administration is a good strategy for harvesting PBSCs in these patients. 

PMID- 23962051
TI  - Serendipity.

PMID- 23962052
TI  - Electrospun hierarchical TiO2 nanorods with high porosity for efficient dye
      sensitized solar cells.
AB  - Ultraporous anatase TiO2 nanorods with a composite structure of mesopores and
      macropores fabricated via a simple microemulsion electrospinning approach were
      first used as photoanode materials for high-efficiency dye-sensitized solar cells
      (DSSCs). The special multiscale porous structure was formed by using low-cost
      paraffin oil microemulsion droplets as the soft template, which can not only
      provide enhanced adsorption sites for dye molecules but also facilitate the
      electrolyte diffusion. The morphology, porosity, and photovoltaic and electron
      dynamic characteristics of the porous TiO2 nanorod based DSSCs were investigated
      in detail by scanning electron microscopy (SEM), N2 sorption measurements,
      current density-voltage (J-V) curves, UV-vis diffuse reflectance spectra,
      electrochemical impedance spectroscopy (EIS), intensity modulated
      photocurrent/photovoltage spectroscopy (IMPS/IMVS), and open-circuit voltage
      decay (OCVD) measurements. The results revealed that, although fewer amounts of
      dyes were anchored on the porous TiO2 nanorod films, they exhibited stronger
      light scattering ability, fast electrolyte diffusion, and extended electron
      lifetime compared to the commercial P25 nanoparticles. A power conversion
      efficiency of 6.07% was obtained for the porous TiO2 nanorod based DSSCs.
      Moreover, this value can be further improved to 8.53% when bilayer structured
      photoanode with porous TiO2 nanorods acting as the light scattering layer was
      constructed. This study demonstrated that the porous TiO2 nanorods can work as
      promising photoanode materials for DSSCs. 

PMID- 23962053
TI  - IGF-1 receptor and IGF binding protein-3 might predict prognosis of patients with
      resectable pancreatic cancer.
AB  - BACKGROUND: The present study aimed to elucidate the clinicopathologic role of
      insulin-like growth factor-1 receptor (IGF1R) and IGF binding protein-3 (IGFBP3)
      in patients with pancreatic cancer. The function of IGFBP3 is controversial,
      because both inhibition and facilitation of the action of IGF as well as IGF
      independent effects have been reported. In this study, IGF1R and IGFBP3
      expression was examined, and their potential roles as prognostic markers in
      patients with pancreatic cancer were evaluated. METHODS: Clinicopathological
      features of 122 patients with curatively resected pancreatic cancer were
      retrospectively reviewed, and expression of IGF1R and IGFBP3 was
      immunohistochemically analyzed. RESULTS: Expression of IGF1R and IGFBP3 was
      observed in 50 (41.0%) and 37 (30.3%) patients, respectively. IGF1R expression
      was significantly associated with histological grade (p = 0.037). IGFBP3
      expression had a significant association with tumor location (p = 0.023), and a
      significant inverse association with venous invasion (p = 0.037). Tumors with
      IGF1R-positive and IGFBP3-negative expression (n = 32) were significantly
      frequently Stage II and III (p = 0.011). The prognosis for IGF1R positive
      patients was significantly poorer than that for IGF1R negative patients (p =
      0.0181). IGFBP3 protein expression did not correlate significantly with patient
      survival. The subset of patients with both positive IGF1R and negative IGFBP3 had
      worse overall survival (8.8 months versus 12.6 months, respectively, p < 0.001).
      CONCLUSION: IGF1R signaling might be associated with tumor aggressiveness, and
      IGFBP3 might show antiproliferative effects in pancreatic cancer. Both high IGF1R
      expression and low IGFBP3 expression represent useful prognostic markers for
      patients with curatively resected pancreatic cancer.

PMID- 23962054
TI  - (-)-Arctigenin as a lead compound for anticancer agent.
AB  - (-)-Arctigenin, an important active constituent of the traditional Chinese herb
      Fructus Arctii, was found to exhibit various bioactivities, so it can be used as
      a good lead compound for further structure modification in order to find a safer
      and more potent medicine. (-)-Arctigenin derivatives 1-5 of (-)-arctingen were
      obtained by modifying with ammonolysis at the lactone ring and sulphonylation at
      C (6') and C (6") and O-demethylation at CH3O-C (3'), CH3O-C (3") and CH3O-C
      (4"), and their anticancer bioactivities were examined.

PMID- 23962055
TI  - The social determinants of multimorbidity in South Africa.
AB  - INTRODUCTION: Multimorbidity is a growing concern worldwide, with approximately 1
      in 4 adults affected. Most of the evidence on multimorbidity, its prevalence and
      effects, comes from high income countries. Not much is known about multimorbidity
      in low income countries, particularly in sub-Saharan Africa. The aim of this
      study was to determine the prevalence of multimorbidity and examine its
      association with various social determinants of health in South Africa. METHOD:
      The data used in this study are taken from the South Africa National Income
      Dynamic Survey (SA-NIDS) of 2008. Multimorbidity was defined as the coexistence
      of two or more chronic diseases in an individual. Multinomial logistic regression
      models were constructed to analyse the relationship between multimorbidity and
      several indicators including socioeconomic status, area of residence and obesity.
      RESULTS: The prevalence of multimorbidity in South Africa was 4% in the adult
      population. Over 70% of adults with multimorbidity were females. Factors
      associated with multimorbidity were social assistance (Odds ratio (OR) 2.35;
      Confidence Interval (CI) 1.59-3.49), residence (0.65; 0.46-0.93), smoking (0.61;
      0.38-0.96); obesity (2.33; 1.60-3.39), depression (1.07; 1.02-1.11) and health
      facility visits (5.14; 3.75-7.05). Additionally, income was strongly positively
      associated with multimorbidity. The findings are similar to observations made in
      studies conducted in developed countries. CONCLUSION: The findings point to a
      potential difference in the factors associated with single chronic disease and
      multimorbidity. Income was consistently significantly associated with
      multimorbidity, but not single chronic diseases. This should be investigated
      further in future research on the factors affecting multimorbidity.

PMID- 23962056
TI  - Diurnal and nutritional adjustments of intracellular Ca2+ release channels and
      Ca2+ ATPases associated with restricted feeding schedules in the rat liver.
AB  - BACKGROUND: Intracellular calcium is a biochemical messenger that regulates part
      of the metabolic adaptations in the daily fed-fast cycle. The aim of this study
      was to characterize the 24-h variations of the liver ryanodine and IP3 receptors
      (RyR and IP3R) as well as of the endoplasmic-reticulum and plasma-membrane Ca2+
      ATPases (SERCA and PMCA) in daytime restricted feeding protocol. METHODS: A
      biochemical and immunohistochemical approach was implemented in this study:
      specific ligand-binding for RyR and IP3R, enzymatic activity (SERCA and PMCA),
      and protein levels and zonational hepatic-distribution were determined by
      immunoblot and immunohistochemistry respectively under conditions of fasting,
      feeding, and temporal food-restriction. RESULTS: Binding assays and immunoblots
      for IP3R1 and 2 showed a peak at the light/dark transition in the ad-libitum (AL)
      group, whereas in the restricted-feeding (RF) group the peak shifted towards the
      food-access time. In the case of RyR binding experiments, both AL and RF groups
      showed a modest elevation during the dark period, with the RF rats exhibiting
      increased binding in response to feeding. The AL group showed 24-h rhythmicity in
      SERCA level; in contrast, RF group showed a pronounced amplitude elevation and a
      peak phase-shift during the light-period in SERCA level and activity. The
      activity of PMCA was constant along day in both groups; PMCA1 levels showed a 24
      h rhythmicity in the RF rats (with a peak in the light period), meanwhile PMCA4
      protein levels showed rhythmicity in both groups. The fasted condition promoted
      an increase in IP3R binding and protein level; re-feeding increased the amount of
      RyR; neither the activity nor expression of SERCA and PMCA protein was affected
      by fasting-re-feeding conditions. Histochemical experiments showed that the
      distribution of the Ca2+-handling proteins, between periportal and pericentral
      zones of the liver, varied with the time of day and the feeding protocol.
      CONCLUSIONS: Our findings show that RF influences mainly the phase and amplitude
      of hepatic IP3R and SERCA rhythms as well as discrete zonational distribution for
      RyR, IP3Rs, SERCA, and PMCA within the liver acinus, suggesting that
      intracellular calcium dynamics could be part of the rheostatic adaptation of the
      liver due to diurnal meal entrainment/food entrained oscillator expression.

PMID- 23962058
TI  - Humanized mice as a model to study human hematopoietic stem cell transplantation.
AB  - Hematopoietic stem cell (HSC) transplantation has the potential to treat a
      variety of human diseases, including genetic deficiencies, immune disorders, and
      to restore immunity following cancer treatment. However, there are several
      obstacles that prevent effective HSC transplantation in humans. These include
      finding a matched donor, having a sufficient number of cells for the transplant,
      and the potency of the cells in the transplant. Ethical issues prevent effective
      research in humans that could provide insight into ways to overcome these
      obstacles. Highly immunodeficient mice can be transplanted with human HSCs and
      this process is accompanied by HSC homing to the murine bone marrow. This is
      followed by stem cell expansion, multilineage hematopoiesis, long-term
      engraftment, and functional human antibody and cellular immune responses. As
      such, humanized mice serve as a model for human HSC transplantation. A variety of
      conditions have been analyzed for their impact on HSC transplantation to produce
      humanized mice, including the type and source of cells used in the transplant,
      the number of cells transplanted, the expansion of cells with various protocols,
      and the route of introduction of cells into the mouse. In this review, we
      summarize what has been learned about HSC transplantation using humanized mice as
      a recipient model and we comment on how these models may be useful to future
      preclinical research to determine more effective ways to expand HSCs and to
      determine their repopulating potential in vivo. 

PMID- 23962057
TI  - Rolofylline, an adenosine A1 receptor antagonist, inhibits osteoclast
      differentiation as an inverse agonist.
AB  - BACKGROUND AND PURPOSE: Adenosine may be generated by hydrolysis of extracellular
      nucleotides by ectonucleotidases, including ectonucleoside triphosphate
      diphosphohydrolase 1 (CD39), ecto-5'-nucleotidase (CD73), nucleotide
      pyrophosphatase phosphodiesterase 1 (NPP-1) and tissue non-specific alkaline
      phosphatase (TNAP). Previous work from our laboratory has uncovered a critical
      role for adenosine A1 receptors (A1 R) in osteoclastogenesis; blockade or
      deletion of these receptors diminishes osteoclast differentiation. Interestingly,
      selective A1 R agonists neither affect basal osteoclastogenesis nor do they
      reverse A1 R antagonist-mediated inhibition of osteoclastogenesis. In this study,
      we determined whether ectonucleotidase-mediated adenosine production was required
      for A1 R antagonist-mediated inhibition, and, when we saw no effect, determined
      whether A1 R was constitutively activated and the antagonist was acting as an
      inverse agonist to diminish osteoclast differentiation. EXPERIMENTAL APPROACH:
      Osteoclast formation derived from wild-type, CD39 knockout (KO), CD73 KO, NPP-1
      KO and TNAP KO mice was examined by tartrate-resistant acid phosphatase staining
      of receptor activator of NF-kappaB ligand-macrophage colony-stimulating factor
      stimulated osteoclasts and osteoclast gene expression (Ctsk, Acp5, MMP-9 and
      NFATc1). Intracellular cAMP concentration was determined by elisa. KEY RESULTS:
      Rolofylline inhibited osteoclast formation in a dose-dependent manner (IC50 = 20
      70 nM) in mice lacking all four of these phosphatases, although baseline
      osteoclast formation was significantly less in precursors from CD73 KO mice.
      Rolofylline (1 MUM) stimulates cAMP production in bone marrow macrophages by
      10.23 +/- 0.89-fold. CONCLUSIONS AND IMPLICATIONS: Based on these findings, we
      hypothesize that the A1 R is constitutively activated in osteoclast precursors,
      thereby diminishing basal AC activity, and that A1 R antagonists act as inverse
      agonists to release A1 R-mediated inhibition of basal AC activity and permit
      osteoclast differentiation. The constitutive activity of A1 R promotes osteoclast
      formation and down-regulation of this activity blocks osteoclast formation.

PMID- 23962059
TI  - Thermal behaviour of procaine and benzocaine Part II: compatibility study with
      some pharmaceutical excipients used in solid dosage forms.
AB  - BACKGROUND: The compatibility study of active substances with excipients finds an
      important role in the domain of pharmaceutical research, being known the fact
      that final formulation is the one administered to the patient. In order to
      evaluate the compatibility between active substance and excipients, different
      analytical techniques can be used, based on their accuracy, reproducibility and
      fastness. RESULTS: Compatibility study of two well-known active substances,
      procaine and benzocaine, with four commonly used excipients, was carried out
      employing thermal analysis (TG/DTG/HF) and Fourier Transform Infrared
      Spectroscopy (UATR-FT-IR). The selected excipients were microcrystalline
      cellulose, lactose monohydrate, magnesium stearate and talc. Equal proportion of
      active substance and excipients (w/w) was utilized in the interaction study. The
      absolute value of the difference between the melting point peak of active
      substances and the one corresponding for the active substances in the analysed
      mixture, as well the absolute value of the difference between the enthalpy of the
      pure active ingredient melting peak and that of its melting peak in the different
      analysed mixtures were chosen as indexes of the drug-excipient interaction
      degree. All the results obtained through thermal analysis were also sustained by
      FT-IR spectroscopy. CONCLUSIONS: The corroboration of data obtained by thermal
      analysis with the ones from FT-IR spectroscopy indicated that no interaction
      occurs between procaine and benzocaine, with microcrystalline cellulose and talc,
      as well for the benzocaine-lactose mixture. Interactions were confirmed between
      procaine and benzocaine respectively and magnesium stearate, and for procaine and
      lactose.

PMID- 23962060
TI  - Lehman syndrome: a new syndrome for pierre robin sequence.
AB  - Lehman syndrome, or lateral meningocele syndrome, is characterized by facial
      dysmorphism, multiple lateral meningoceles, and skeletal abnormalities. Only nine
      cases have been described. We present a case of a 2-year-old boy presenting with
      micrognathia, glossoptosis, and hypertelorism as well as associated severe
      obstructive sleep apnea. He was submitted to bilateral mandibular distraction
      with external nonresorbable devices to correct Pierre Robin sequence (PRS).
      Later, multiple lateral meningoceles were identified, and a diagnosis of Lehman
      syndrome was made. Lehman syndrome must be considered in syndromic infants with
      PRS. Distraction osteogenesis is a safe procedure that is effective as a first
      choice in the treatment of patients with Lehman syndrome presenting with
      micrognathia.

PMID- 23962061
TI  - Large-scale parentage analysis reveals reproductive patterns and heritability of
      spawn timing in a hatchery population of steelhead (Oncorhynchus mykiss).
AB  - Understanding life history traits is an important first step in formulating
      effective conservation and management strategies. The use of artificial
      propagation and supplementation as such a strategy can have numerous effects on
      the supplemented natural populations and minimizing life history divergence is
      crucial in minimizing these effects. Here, we use single nucleotide polymorphism
      (SNP) genotypes for large-scale parentage analysis and pedigree reconstruction in
      a hatchery population of steelhead, the anadromous form of rainbow trout. Nearly
      complete sampling of the broodstock for several consecutive years in two hatchery
      programmes allowed inference about multiple aspects of life history.
      Reconstruction of cohort age distribution revealed a strong component of fish
      that spawn at 2 years of age, in contrast to programme goals and distinct from
      naturally spawning steelhead in the region, which raises a significant
      conservation concern. The first estimates of variance in family size for
      steelhead in this region can be used to calculate effective population size and
      probabilities of inbreeding, and estimation of iteroparity rate indicates that it
      is reduced by hatchery production. Finally, correlations between family members
      in the day of spawning revealed for the first time a strongly heritable component
      to this important life history trait in steelhead and demonstrated the potential
      for selection to alter life history traits rapidly in response to changes in
      environmental conditions. Taken together, these results demonstrate the
      extraordinary promise of SNP-based pedigree reconstruction for providing
      biological inference in high-fecundity organisms that is not easily achievable
      with traditional physical tags.

PMID- 23962062
TI  - Parents who refuse to vaccinate their infants: paediatricians' feelings and
      treatment intentions.
AB  - AIM: The aim of this study was to evaluate paediatricians' attitudes and emotions
      towards parents who refuse to vaccinate their infants and to assess their
      reactions, suggestions and practices. DESIGN: The study group consisted of 376
      paediatricians in Israel, who completed the emailed research questionnaire
      anonymously. RESULTS: Although the vast majority of paediatricians agreed that
      vaccination was in the baby's best interest (92.2%), only a small percentage
      (3.5%) felt that there should be some scientific justification behind a parent's
      refusal. The majority (70.7%) of those surveyed expressed negative feelings
      towards refusing parents. Despite this, more than a third (36.9%) agreed that
      parents have the right to decide (28.9% disagreed) and a third (36.8%) agreed
      that vaccinations should be officially enforced (35.8% disagreed). Only a very
      small percentage of the paediatricians (1.8%) said they would object to treating
      infants who had not been vaccinated. CONCLUSION: Paediatricians face a conflict
      between two opposing values: the importance of immunization versus the parents'
      rights to decide what is best for their own child. Therefore, they are in favour
      of gentle persuasion or official enforcement. We believe that experts in modern
      communication could help paediatricians to convey the positive benefits of
      vaccination to parents.

PMID- 23962063
TI  - Pathological generosity: an atypical impulse control disorder after a left
      subcortical stroke.
AB  - Changes in socio-emotional behavior and conduct, which are characteristic
      symptoms of frontal lobe damage, have less often been described in patients with
      focal subcortical injuries. We report on a case of pathological generosity
      secondary to a left lenticulocapsular stroke with hypoperfusion of several
      anatomically intact cortical areas. A 49-year-old man developed excessive and
      persistent generosity as he recovered from a left lenticulocapsular hematoma. His
      symptoms resembled an impulse control disorder. (99m)Tc-HMPAO SPECT demonstrated
      hypoperfusion mostly in the ipsilateral striatum, dorsolateral, and orbitofrontal
      cortex. This case study adds pathological generosity to the range of behavioral
      changes that may result from discrete unilateral lesions of the lenticular
      nucleus and nearby pathways. In our particular case, post-stroke pathological
      generosity was not ascribable to disinhibition, apathy, mania, or depression.
      Because pathological generosity may lead to significant distress and financial
      burden upon patients and their families, it may warrant further consideration as
      a potential type of impulse control disorder. 

PMID- 23962064
TI  - Hypoxia-inducible factors promote alveolar development and regeneration.
AB  - Understanding how alveoli and the underlying capillary network develop and how
      these mechanisms are disrupted in disease states is critical for developing
      effective therapies for lung regeneration. Recent evidence suggests that lung
      angiogenesis promotes lung development and repair. Vascular endothelial growth
      factor (VEGF) preserves lung angiogenesis and alveolarization in experimental O2
      induced arrested alveolar growth in newborn rats, but combined VEGF+angiopoietin
      1 treatment is necessary to correct VEGF-induced vessel leakiness. Hypoxia
      inducible factors (HIFs) are transcription factors that activate multiple O2
      sensitive genes, including those encoding for angiogenic growth factors, but
      their role during postnatal lung growth is incompletely understood. By inducing
      the expression of a range of angiogenic factors in a coordinated fashion, HIF may
      orchestrate efficient and safe angiogenesis superior to VEGF. We hypothesized
      that HIF inhibition impairs alveolarization and that HIF activation regenerates
      irreversible O2-induced arrested alveolar growth. HIF inhibition by intratracheal
      dominant-negative adenovirus (dnHIF-1alpha)-mediated gene transfer or chetomin
      decreased lung HIF-1alpha, HIF-2alpha, and VEGF expression and led to air space
      enlargement and arrested lung vascular growth. In experimental O2-induced
      arrested alveolar growth in newborn rats, the characteristic features of air
      space enlargement and loss of lung capillaries were associated with decreased
      lung HIF-1alpha and HIF-2alpha expression. Intratracheal administration of Ad.HIF
      1alpha restored HIF-1alpha, endothelial nitric oxide synthase, VEGF, VEGFR2, and
      Tie2 expression and preserved and rescued alveolar growth and lung capillary
      formation in this model. HIFs promote normal alveolar development and may be
      useful targets for alveolar regeneration. 

PMID- 23962065
TI  - Genetic characterization of naturally occurring Rhizobium meliloti populations
      and their potential to form effective symbioses with lucerne.
AB  - Genetic characterization by Randomly Amplified Polymorphic DNA (RAPD)
      fingerprinting was employed to study the status of Rhizobium meliloti populations
      inhabiting nodules of lucerne. Rhizobium strains were isolated from nodules
      harvested from plants growing in inoculated or uninoculated experimental plots,
      uninoculated commercial fields and from lucerne grown in pots containing soils of
      different origin. Dry matter analyses were recorded and rhizobia were assessed
      for relative genetic diversity between treatments. Inoculated and uninoculated
      soils did not differ in terms of dry matter production, and lucerne grew, and was
      adequately nodulated, in soils with no history of lucerne cultivation. These
      findings, and the demonstration that there is a rich genetic diversity of Rh.
      meliloti in these soils, show that it is not always necessary to apply a standard
      commercial inoculant. 

PMID- 23962066
TI  - Selective sugar consumption by apiculate yeasts.
AB  - Selective consumption of glucose and fructose among apiculate yeasts was
      evaluated. Results showed that Hanseniaspora guilliermondii and H. uvarum type
      strains were fructosophilic, unlike the other type strains. The difference in
      glucose and fructose use was confirmed in different media and throughout sugar
      consumption. Selective consumption of fructose is widely diffused among apiculate
      wine yeasts and could positively interfere with fermentation behaviour of
      Saccharomyces cerevisiae. 

PMID- 23962068
TI  - Fabrication of alpha-Fe2O3 nanorod/RGO composite: a novel hybrid photocatalyst
      for phenol degradation.
AB  - We report herein the fabrication of a hematite nanorod-graphene composite (alpha
      Fe2O3 nanorod/RGO) via a facile template-free hydrothermal route with an aim to
      improve the photocatalytic efficiency of the alpha-Fe2O3 nanorod. The structural
      and morphological characterizations of the as-prepared composites were carried
      out using X-ray diffraction, Raman spectra, X-ray photoelectron spectroscopy,
      scanning electron microscopy, transmission electron microscopy, N2 adsorption
      desorption, etc. The alpha-Fe2O3 nanorods were well-decorated on the surface of
      the graphene sheets, which helps in electron transfer from alpha-Fe2O3 to
      graphene and hence can delay the recombination process, leading to the
      improvement in photocatalytic activity. The composite containing 5 wt % RGO and
      alpha-Fe2O3 nanorods shows a 4-fold enhancement in the photocatalytic activity.
      The performance of photocatalytic activity was discussed in light of surface
      area, interaction between nanorods and graphene nanosheets, synergism between
      alpha-Fe2O3 nanorods and RGO sheets, light-harvesting properties of the
      composites, photoluminescence spectra, photocurrent measurement, and hydroxyl
      radical formation. 

PMID- 23962067
TI  - Surface reengineering of RPA70N enables cocrystallization with an inhibitor of
      the replication protein A interaction motif of ATR interacting protein.
AB  - Replication protein A (RPA) is the primary single-stranded DNA (ssDNA) binding
      protein in eukaryotes. The N-terminal domain of the RPA70 subunit (RPA70N)
      interacts via a basic cleft with a wide range of DNA processing proteins,
      including several that regulate DNA damage response and repair. Small molecule
      inhibitors that disrupt these protein-protein interactions are therefore of
      interest as chemical probes of these critical DNA processing pathways and as
      inhibitors to counter the upregulation of DNA damage response and repair
      associated with treatment of cancer patients with radiation or DNA-damaging
      agents. Determination of three-dimensional structures of protein-ligand complexes
      is an important step for elaboration of small molecule inhibitors. However,
      although crystal structures of free RPA70N and an RPA70N-peptide fusion construct
      have been reported, RPA70N-inhibitor complexes have been recalcitrant to
      crystallization. Analysis of the P61 lattice of RPA70N crystals led us to
      hypothesize that the ligand-binding surface was occluded. Surface reengineering
      to alter key crystal lattice contacts led to the design of RPA70N E7R, E100R, and
      E7R/E100R mutants. These mutants crystallized in a P212121 lattice that clearly
      had significant solvent channels open to the critical basic cleft. Analysis of X
      ray crystal structures, target peptide binding affinities, and (15)N-(1)H
      heteronuclear single-quantum coherence nuclear magnetic resonance spectra showed
      that the mutations do not result in perturbations of the RPA70N ligand-binding
      surface. The success of the design was demonstrated by determining the structure
      of RPA70N E7R soaked with a ligand discovered in a previously reported molecular
      fragment screen. A fluorescence anisotropy competition binding assay revealed
      this compound can inhibit the interaction of RPA70N with the peptide binding
      motif from the DNA damage response protein ATRIP. The implications of the results
      are discussed in the context of ongoing efforts to design RPA70N inhibitors. 

PMID- 23962069
TI  - Successful living-related kidney transplantation in a boy with inherited
      dysfibrinogenemia.
AB  - In kidney transplantation, it is essential to avoid acute vascular complications,
      such as hemorrhage and renal vascular thrombosis, which may often lead to
      allograft loss. Inherited dysfibrinogenemia is a rare coagulation disorder with a
      wide spectrum of clinical manifestations, such as excessive bleeding and
      thrombosis. A 12-yr-old boy, previously diagnosed with renal hypodysplasia, was
      found to have reduced fibrinogen concentrations. Coagulation tests assessing
      surgical risk during kidney transplantation showed a discrepancy between
      functional and immunologic fibrinogen concentrations. Gene analysis confirmed
      inherited dysfibrinogenemia, with a heterozygous mutation in FGA (Aalpha
      Arg16His) in the patient and his mother. Based on the molecular and functional
      properties of the mutation, and a familial phenotype, in which his aunt had
      experienced a previous bleeding episode, the patient was considered at greater
      risk of bleeding than of thrombosis. The patient was administered fibrinogen
      concentrate before surgery, and kidney transplantation was performed with his
      father as the organ donor. The patient received additional prophylactic infusions
      of fibrinogen concentrate postoperatively, and his postoperative course was
      uneventful. Accurate diagnosis of dysfibrinogenemia, including gene analysis, is
      important for correctly managing patients with this coagulation disorder who are
      undergoing kidney transplantation. 

PMID- 23962070
TI  - Poly-use multi-level sampling system for soil-gas transport analysis in the
      vadose zone.
AB  - Soil-gas turnover is important in the global cycling of greenhouse gases. The
      analysis of soil-gas profiles provides quantitative information on below-ground
      turnover and fluxes. We developed a poly-use multi-level sampling system (PMLS)
      for soil-gas sampling, water-content and temperature measurement with high depth
      resolution and minimal soil disturbance. It is based on perforated access tubes
      (ATs) permanently installed in the soil. A multi-level sampler allows extraction
      of soil-gas samples from 20 locations within 1 m depth, while a capacitance probe
      is used to measure volumetric water contents. During idle times, the ATs are
      sealed and can be equipped with temperature sensors. Proof-of-concept experiments
      in a field lysimeter showed good agreement of soil-gas samples and water-content
      measurements compared with conventional techniques, while a successfully
      performed gas-tracer test demonstrated the feasibility of the PMLS to determine
      soil-gas diffusion coefficients in situ. A field application of the PMLS to
      quantify oxidation of atmospheric CH4 in a field lysimeter and in the forefield
      of a receding glacier yielded activity coefficients and soil-atmosphere fluxes
      well in agreement with previous studies. With numerous options for customization,
      the presented tool extends the methodological choices to investigate soil-gas
      transport in the vadose zone. 

PMID- 23962071
TI  - Peripheral blood monocyte-to-lymphocyte ratio at study enrollment predicts
      efficacy of the RTS,S malaria vaccine: analysis of pooled phase II clinical trial
      data.
AB  - BACKGROUND: RTS,S is the most advanced candidate malaria vaccine but it is only
      partially protective and the causes of inter-individual variation in efficacy are
      poorly understood. Here, we investigated whether peripheral blood monocyte-to
      lymphocyte ratios (ML ratio), previously shown to correlate with clinical malaria
      risk, could account for differences in RTS,S efficacy among phase II trial
      participants in Africa. METHODS: Of 11 geographical sites where RTS,S has been
      evaluated, pre-vaccination ML ratios were only available for trial participants
      in Kilifi, Kenya (N = 421) and Lambarene, Gabon (N = 189). Using time to first
      clinical malaria episode as the primary endpoint we evaluated the effect of
      accounting for ML ratio on RTS,S vaccine efficacy against clinical malaria by Cox
      regression modeling. RESULTS: The unadjusted efficacy of RTS,S in this combined
      dataset was 47% (95% confidence interval (CI) 26% to 62%, P <0.001). However,
      RTS,S efficacy decreased with increasing ML ratio, ranging from 67% (95% CI 64%
      to 70%) at an ML ratio of 0.1 to 5% (95% CI -3% to 13%) at an ML ratio of 0.6.
      The statistical interaction between RTS,S vaccination and ML ratio was still
      evident after adjustment for covariates associated with clinical malaria risk in
      this dataset. CONCLUSION: The results suggest that stratification of study
      participants by ML ratio, easily measured from full differential blood counts
      before vaccination, might help identify children who are highly protected and
      those that are refractory to protection with the RTS,S vaccine. Identifying
      causes of low vaccine efficacy among individuals with high ML ratio could inform
      strategies to improve overall RTS,S vaccine efficacy. TRIAL REGISTRATION:
      ClinicalTrials.Gov numbers NCT00380393 and NCT00436007.

PMID- 23962072
TI  - Responsiveness of eyes with polypoidal choroidal vasculopathy with choroidal
      hyperpermeability to intravitreal ranibizumab.
AB  - BACKGROUND: To determine the role played by vascular endothelial growth factor
      (VEGF) in polypoidal choroidal vasculopathy (PCV) based on an interventional
      immunology theory. METHODS: Eyes with PCV were divided in a masked fashion into
      those with choroidal hyperpermeability (HP group) and those with normal choroidal
      permeability (NP group) based on the indocyanine green angiograms. The inter
      rater agreement rate was evaluated using Fleiss' kappa. Patients were treated by
      intravitreal ranibizumab (IVB). The central choroidal thickness and central
      foveal thickness (CFT) at the baseline and 7 days after the treatment were
      measured by optical coherence tomography. RESULTS: Among the 57 consecutive eyes
      diagnosed with PCV, 42 eyes of 42 patients met the inclusion criteria (21 eyes/HP
      group vs 21 eyes /NP group). Central choroidal thickness in HP group was
      significantly thicker than that in the NP group (P < .001, Mann-Whitney U test).
      The inter-rater agreement was high with a Fleiss' kappa = 0.95, P < .0001. The
      percentage reduction in the CFT in HP group (14.0%) was significantly less than
      that in NP group (20.4%; P = .013, Mann-Whitney U test). CONCLUSIONS: Eyes with
      PCV that are associated with choroidal hyper-permeability may not be strongly
      associated with VEGF-related pathology, and may not respond favorably to anti
      VEGF monotherapy.

PMID- 23962073
TI  - Significance of CD71 expression by flow cytometry in diagnosis of acute leukemia.
AB  - In this study we investigated the significance of CD71 (transferrin receptor 1,
      TfR-1) as a flow cytometric marker in the diagnosis of acute leukemia (AL). A
      total of 105 patients with AL were enrolled. Poorly differentiated acute myeloid
      leukemias (AMLs) (including minimally differentiated AML, AML without maturation,
      AML with maturation, acute myelomonocytic leukemia) tended to express high levels
      of CD71 on leukemic cells, while partially differentiated AML (including acute
      promyelocytic leukemia and acute monocytic leukemia) often expressed low levels
      of CD71 on leukemic cells (p < 0.05, compared to poorly differentiated AML). B
      cell acute lymphoblastic leukemia (B-ALL) expressed low levels of CD71 on
      leukemic cells, significantly lower than AML, mixed phenotype acute leukemia
      (MPAL) and normal bone marrow blasts (p < 0.05). In the seven cases of acute
      erythroid leukemia (AEL), leukemic cells rarely expressed CD71, with the mean
      CD71 expression level significantly lower than that of acute megakaryocytic
      leukemia (p < 0.05), and also lower than that of poorly differentiated AML and
      normal blasts but without statistical significance. CD71 may not be a specific
      marker for AEL leukemic cells. During the process from myeloid dysplasia to
      apparent leukemic cells, both CD71 and CD34 gradually increased. Consequently,
      the presence of leukemic cell subsets with variable levels of CD71 and CD34 may
      be useful for understanding the dynamic processes involved in the clonal
      development seen in leukemias.

PMID- 23962074
TI  - Aqp1 enhances migration of bone marrow mesenchymal stem cells through regulation
      of FAK and beta-catenin.
AB  - Bone marrow mesenchymal stem cells (MSCs) have the potential to migrate to the
      site of injury and regulate the repair process. Aquaporin 1 (Aqp1) is a water
      channel molecule and a regulator of endothelial cell migration. To study the role
      of Apq1 in MSC migration, we manipulated the expression of the Aqp1 gene in MSCs
      and explored its effects on MSC migration both in vitro and in vivo.
      Overexpression of Aqp1 promoted MSC migration, while depletion of Aqp1 impaired
      MSC migration in vitro. When the green fluorescent protein (GFP) labeled Aqp1
      overexpressing MSCs were systemically injected into rats with a femoral fracture,
      there were significantly more GFP-MSCs found at the fracture gap in the Aqp1-GFP
      MSC-treated group compared to the GFP-MSC group. To elucidate the underlying
      mechanism, we screened several migration-related regulators. The results showed
      that beta-catenin and focal adhesion kinase (FAK) were upregulated in the Aqp1
      MSCs and downregulated in the Aqp1-depleted MSCs, while C-X-C chemokine receptor
      type 4 had no change. Furthermore, beta-catenin and FAK were co
      immunoprecipitated with Aqp1, and depletion of FAK abolished the Aqp1 effects on
      MSC migration. This study demonstrates that Aqp1 enhances MSC migration ability
      mainly through the FAK pathway and partially through the beta-catenin pathway.
      Our finding suggests a novel function of Aqp1 in governing MSC migration, and
      this may aid MSC therapeutic applications. 

PMID- 23962075
TI  - Two new ursolic acid saponins from Morina nepalensis var. alba Hand-Mazz.
AB  - A saponin-enriched fraction was prepared from the EtOH extract of the whole plant
      of Morina nepalensis var. alba Hand-Mazz. It showed alpha-glucosidase inhibitory
      activity, from which two new triterpene saponins (1 and 2), along with one known
      saponin (3), were isolated. The structures of the new saponins were identified by
      spectroscopic analysis, including extensive 1D and 2D NMR techniques and
      hydrolysis followed by chromatographic analysis. The three saponins were assayed
      for alpha-glucosidase inhibitory activities. 

PMID- 23962076
TI  - Inequalities in multimorbidity in South Africa.
AB  - BACKGROUND: Very little is known about socioeconomic related inequalities in
      multimorbidity, especially in developing countries. Traditionally, studies on
      health inequalities have mainly focused on a single disease condition or
      different conditions in isolation. This paper examines socioeconomic inequality
      in multimorbidity in illness and disability in South Africa between 2005 and
      2008. METHODS: Data were drawn from the 2005, 2006, 2007, and 2008 rounds of the
      nationally representative annual South African General Household Surveys (GHS).
      Indirectly standardised concentration indices were used to assess socioeconomic
      inequality. A proxy index of socioeconomic status was constructed, for each year,
      using a selected set of variables that are available in all the GHS rounds.
      Multimorbidity in illness and disability were constructed using data on nine
      illnesses and six disabilities contained in the GHS. RESULTS: Multimorbidity
      affects a substantial number of South Africans. Most often, based on the nine
      illness conditions and six disability conditions considered, multimorbidity in
      illness and multimorbidity in disability are each found to involve only two
      conditions. In 2008 in South Africa, the multimorbidity that affected the
      greatest number of individuals (0.6% of the population) combined high blood
      pressure (BP) with at least one other illness. The combination of sexually
      transmitted diseases (STDs) and other condition or conditions is the least
      reported (i.e. 0.02% of the population). Between 2005 and 2008, multimorbidity in
      illness and disability is more prevalent among the poor; in disabilities this is
      yet more consistent. The concentration index of multiple illnesses in 2005 and
      2008 are -0.0009 and -0.0006 respectively. The corresponding values for multiple
      disabilities are -0.0006 and -0.0006 respectively. CONCLUSION: While there is a
      dearth of information on the socioeconomic distribution of multimorbidity in many
      developing countries, this paper has shown that its distribution in South Africa
      indicates that the poor bear a greater burden of multimorbidity. This is more so
      for disability than for illness. This paper argues that, given the high burden
      and skewed socioeconomic distribution of multimorbidity, there is a need to
      design policies to address this situation. Further, there is a need to design
      surveys that specifically assess multimorbidity.

PMID- 23962077
TI  - Supporting children and young people in hospital.

PMID- 23962078
TI  - Writing for publication in Issues in Comprehensive Pediatric Nursing.
AB  - This article is designed to help children's and young people's nurses and health
      care professionals working with children to prepare a manuscript for publication
      in Issues in Comprehensive Pediatric Nursing. A suggested format based on 11
      simple steps which details the specific architecture expected for the preparation
      of a range of manuscripts. 

PMID- 23962079
TI  - Reversible inhibition of the glycine transporter GlyT2 circumvents acute toxicity
      while preserving efficacy in the treatment of pain.
AB  - BACKGROUND AND PURPOSE: Available medications for chronic pain provide only
      partial relief and often cause unacceptable side effects. There is therefore a
      need for novel molecular targets to develop new therapeutics with improved
      efficacy and tolerability. Despite encouraging efficacy data in rodents with
      inhibitors of the neuronal glycine transporter-2 (GlyT2), there are also some
      reports of toxicity and their development was discontinued. EXPERIMENTAL
      APPROACH: In order to clarify the possibility of targeting GlyT2 for the
      treatment of pain, we have used an integrated approach comprising in vitro
      pharmacology, selectivity, bioavailability, in vivo efficacy and safety
      assessment to analyse the properties and efficacy of ALX-1393 and Org-25543, the
      two published GlyT2 inhibitors from which in vivo data are available. KEY
      RESULTS: We report that these compounds have a different set of undesirable
      properties that limit their usefulness as pharmacological tools. Importantly, we
      discover that inhibitors of GlyT2 can exert an apparent reversible or
      irreversible inhibition of the transporter and describe a new class of reversible
      GlyT2 inhibitors that preserves efficacy while avoiding acute toxicity.
      CONCLUSIONS AND IMPLICATIONS: Our pharmacological comparison of two closely
      related GlyT2 inhibitors with different modes of inhibition provides important
      insights into their safety and efficacy profiles, uncovering that in the presence
      of a GlyT2 mechanism-based toxicity, reversible inhibitors might allow a
      tolerable balance between efficacy and toxicity. These findings shed light into
      the drawbacks associated with the early GlyT2 inhibitors and describe a new
      mechanism that might serve as the starting point for new drug development.

PMID- 23962080
TI  - Different genotypes of a functional polymorphism of the TSHR gene are associated
      with the development and severity of Graves' and Hashimoto's diseases.

PMID- 23962081
TI  - Crystal-facet-dependent metallization in electrolyte-gated rutile TiO2 single
      crystals.
AB  - The electric-field-induced metallization of insulating oxides is a powerful means
      of exploring and creating exotic electronic states. Here we show by the use of
      ionic liquid gating that two distinct facets of rutile TiO2, namely, (101) and
      (001), show clear evidence of metallization, with a disorder-induced metal
      insulator transition at low temperatures, whereas two other facets, (110) and
      (100), show no substantial effects. This facet-dependent metallization can be
      correlated with the surface energy of the respective crystal facet and, thus, is
      consistent with oxygen vacancy formation and diffusion that results from the
      electric fields generated within the electric double layers at the ionic
      liquid/TiO2 interface. These effects take place at even relatively modest gate
      voltages. 

PMID- 23962082
TI  - Active components of ginger potentiate beta-agonist-induced relaxation of airway
      smooth muscle by modulating cytoskeletal regulatory proteins.
AB  - beta-Agonists are the first-line therapy to alleviate asthma symptoms by acutely
      relaxing the airway. Purified components of ginger relax airway smooth muscle
      (ASM), but the mechanisms are unclear. By elucidating these mechanisms, we can
      explore the use of phytotherapeutics in combination with traditional asthma
      therapies. The objectives of this study were to: (1) determine if 6-gingerol, 8
      gingerol, or 6-shogaol potentiate beta-agonist-induced ASM relaxation; and (2)
      define the mechanism(s) of action responsible for this potentiation. Human ASM
      was contracted in organ baths. Tissues were relaxed dose dependently with beta
      agonist, isoproterenol, in the presence of vehicle, 6-gingerol, 8-gingerol, or 6
      shogaol (100 MUM). Primary human ASM cells were used for cellular experiments.
      Purified phosphodiesterase (PDE) 4D or phospholipase C beta enzyme was used to
      assess inhibitory activity of ginger components using fluorescent assays. A G
      LISA assay was used to determine the effects of ginger constituents on Ras
      homolog gene family member A activation. Significant potentiation of
      isoproterenol-induced relaxation was observed with each of the ginger
      constituents. 6-Shogaol showed the largest shift in isoproterenol half-maximal
      effective concentration. 6-Gingerol, 8-gingerol, or 6-shogaol significantly
      inhibited PDE4D, whereas 8-gingerol and 6-shogaol also inhibited phospholipase C
      beta activity. 6-Shogaol alone inhibited Ras homolog gene family member A
      activation. In human ASM cells, these constituents decreased phosphorylation of
      17-kD protein kinase C-potentiated inhibitory protein of type 1 protein
      phosphatase and 8-gingerol decreased myosin light chain phosphorylation. Isolated
      components of ginger potentiate beta-agonist-induced relaxation in human ASM.
      This potentiation involves PDE4D inhibition and cytoskeletal regulatory proteins.
      Together with beta-agonists, 6-gingerol, 8-gingerol, or 6-shogaol may augment
      existing asthma therapy, resulting in relief of symptoms through complementary
      intracellular pathways. 

PMID- 23962083
TI  - Comparison of historical bottleneck effects and genetic consequences of re
      introduction in a critically endangered island passerine.
AB  - Re-introduction is an important tool for recovering endangered species; however,
      the magnitude of genetic consequences for re-introduced populations remains
      largely unknown, in particular the relative impacts of historical population
      bottlenecks compared to those induced by conservation management. We characterize
      14 microsatellite loci developed for the Seychelles paradise flycatcher and use
      them to quantify temporal and spatial measures of genetic variation across a 134
      year time frame encompassing a historical bottleneck that reduced the species to
      ~28 individuals in the 1960s, through the initial stages of recovery and across a
      second contemporary conservation-introduction-induced bottleneck. We then
      evaluate the relative impacts of the two bottlenecks, and finally apply our
      findings to inform broader re-introduction strategy. We find a temporal trend of
      significant decrease in standard measures of genetic diversity across the
      historical bottleneck, but only a nonsignificant downward trend in number of
      alleles across the contemporary bottleneck. However, accounting for the different
      timescales of the two bottlenecks (~40 historical generations versus <1
      contemporary generation), the loss of genetic diversity per generation is greater
      across the contemporary bottleneck. Historically, the flycatcher population was
      genetically structured; however, extinction on four of five islands has resulted
      in a homogeneous contemporary population. We conclude that severe historical
      bottlenecks can leave a large footprint in terms of sheer quantity of genetic
      diversity lost. However, severely depleted genetic diversity does not render a
      species immune to further genetic erosion upon re-introduction. In some cases,
      the loss of genetic diversity per generation can, initially at least, be greater
      across re-introduction-induced bottlenecks. 

PMID- 23962084
TI  - Vascular endothelial growth factor single-nucleotide polymorphism in gallbladder
      cancer.
AB  - BACKGROUND AND AIM: Angiogenesis plays a key role in growth, progression, and
      metastasis of various cancers. Vascular endothelial growth factor (VEGF)
      polymorphism has been associated with several cancers. Role of VEGF has not been
      reported in gallbladder cancer (GBC). Present study was designed to investigate
      the role of VEGF polymorphism in GBC and in other (benign) gallbladder diseases,
      that is chronic cholecystitis (CC) and xanthogranulomatous cholecystitis (XGC).
      METHODS: Blood samples were collected from 195 GBC, 140 CC, and 47 XGC patients
      and 300 normal healthy controls. VEGF polymorphisms were investigated using
      amplification refractory mutation system polymerase chain reaction for
      g.43737830A>G and g.3437A>C, polymerase chain reaction-restriction fragment
      length polymorphism for c.*237C>T, and g.43736418delTinsG amplified by polymerase
      chain reaction. RESULTS: At g.43737830A>G, GA genotype showed susceptibility
      (odds ratio [OR] = 1.65 and OR = 1.68) and GG genotype showed protective
      association (OR = 0.58 and OR = 0.50) with GBC and CC. Allele A of VEGF
      g.43737830A>G was risk associated with GBC and CC (OR = 1.48 and OR = 1.70),
      while G allele was risk protective for GBC and CC (OR = 0.67 and OR = 0.58). At
      g.3437A>C, genotype CA was risk protective for GBC (OR = 0.61). TT genotype of
      c.*237C>T was susceptible for GBC and CC (OR = 2.59 and OR = 3.48), while CC
      genotype was risk protective for GBC and CC (OR = 0.61 and OR = 0.34). T allele
      of c.*237C>T polymorphism was risk associated with GBC and CC (OR = 1.63 and OR =
      2.90), while C allele was risk protective for GBC and CC (OR = 0.38 and OR =
      0.28). Haplotype I-C-A-C was risk protective for GBC (OR = 0.27). CONCLUSION: The
      present study suggests that c.*237C>T and g.43737830A>G polymorphisms are useful
      markers of susceptibility to GBC.

PMID- 23962085
TI  - Secretion and assembly of functional mini-cellulosomes from synthetic chromosomal
      operons in Clostridium acetobutylicum ATCC 824.
AB  - BACKGROUND: Consolidated bioprocessing (CBP) is reliant on the simultaneous
      enzyme production, saccharification of biomass, and fermentation of released
      sugars into valuable products such as butanol. Clostridial species that produce
      butanol are, however, unable to grow on crystalline cellulose. In contrast, those
      saccharolytic species that produce predominantly ethanol, such as Clostridium
      thermocellum and Clostridium cellulolyticum, degrade crystalline cellulose with
      high efficiency due to their possession of a multienzyme complex termed the
      cellulosome. This has led to studies directed at endowing butanol-producing
      species with the genetic potential to produce a cellulosome, albeit by localising
      the necessary transgenes to unstable autonomous plasmids. Here we have explored
      the potential of our previously described Allele-Coupled Exchange (ACE)
      technology for creating strains of the butanol producing species Clostridium
      acetobutylicum in which the genes encoding the various cellulosome components are
      stably integrated into the genome. RESULTS: We used BioBrick2 (BB2) standardised
      parts to assemble a range of synthetic genes encoding C. thermocellum
      cellulosomal scaffoldin proteins (CipA variants) and glycoside hydrolases (GHs,
      Cel8A, Cel9B, Cel48S and Cel9K) as well as synthetic cellulosomal operons that
      direct the synthesis of Cel8A, Cel9B and a truncated form of CipA. All synthetic
      genes and operons were integrated into the C. acetobutylicum genome using the
      recently developed ACE technology. Heterologous protein expression levels and
      mini-cellulosome self-assembly were assayed by western blot and native PAGE
      analysis. CONCLUSIONS: We demonstrate the successful expression, secretion and
      self-assembly of cellulosomal subunits by the recombinant C. acetobutylicum
      strains, providing a platform for the construction of novel cellulosomes.

PMID- 23962086
TI  - Unawareness of deficits in ischemic injury: role of the cingulate cortex.
AB  - Reduced awareness of illness is a well-known phenomenon that has been studied in
      patients with vascular disease, but the precise nature of their executive
      dysfunction is an intriguing question that still has to be resolved. It would be
      particularly interesting to study patients with reduced awareness of disease
      possibly related to vascular lesions of the prefrontal cortex. Due to the
      clinical importance of the case, here we present a patient with a selective right
      anterior cingulate ischemic injury and impaired awareness of deficits. We suggest
      that the cingulo-frontal area dysfunction may represent one of the corresponding
      neurobiological substrates of his persistent unawareness, which has not yet been
      evaluated in the literature on patients with acquired brain injury (ABI). 

PMID- 23962087
TI  - Interaction of 14-3-3zeta with microtubule-associated protein tau within
      Alzheimer's disease neurofibrillary tangles.
AB  - Alzheimer's disease (AD) is characterized by the presence of abnormal, straight
      filaments and paired helical filaments (PHFs) that are coated with amorphous
      aggregates. When PHFs are treated with alkali, they untwist and form filaments
      with a ribbonlike morphology. Tau protein is the major component of all of these
      ultrastructures. 14-3-3zeta is present in NFTs and is significantly upregulated
      in AD brain. The molecular basis of the association of 14-3-3zeta within NFTs and
      the pathological significance of its association are not known. In this study, we
      have found that 14-3-3zeta is copurified and co-immunoprecipitates with tau from
      NFTs of AD brain extract. In vitro, tau binds to both phosphorylated and
      nonphosphorylated tau. When incubated with 14-3-3zeta, tau forms amorphous
      aggregates, single-stranded, straight filaments, ribbonlike filaments, and PHF
      like filaments, all of which resemble the corresponding ultrastructures found in
      AD brain. Immuno-electron microscopy determined that both tau and 14-3-3zeta are
      present in these ultrastructures and that they are formed in an incubation time
      dependent manner. Amorphous aggregates are formed first. As the incubation time
      increases, the size of amorphous aggregates increases and they are incorporated
      into single-stranded filaments. Single-stranded filaments laterally associate to
      form double-stranded, ribbonlike, and PHF-like filaments. Both tau and
      phosphorylated tau aggregate in a similar manner when they are incubated with 14
      3-3zeta. Our data suggest that 14-3-3zeta has a role in the fibrillization of tau
      in AD brain, and that tau phosphorylation does not affect 14-3-3zeta-induced tau
      aggregation. 

PMID- 23962088
TI  - ZnO electron field emitters on three-dimensional patterned carbon nanotube
      framework.
AB  - A three-dimensional patterned CNT framework was prepared in a thermal chemical
      vapor deposition system. ZnO nanoneedles with different areal density were
      subsequently grown on it via hydrothermal method. By combining the advantages of
      high aspect ratio, more effective emission sites with minimized screen effect and
      good Ohmic contact between ZnO nanoneedles and CNT framework, the ZnO/CNT
      hierarchical nanostructures with medium areal density exhibit a favorable FE
      performance which makes it promising candidate for cold cathode nanomaterials. 

PMID- 23962089
TI  - Tumor necrosis factor alpha antagonism improves neurological recovery in murine
      intracerebral hemorrhage.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating stroke subtype
      characterized by a prominent neuroinflammatory response. Antagonism of pro
      inflammatory cytokines by specific antibodies represents a compelling therapeutic
      strategy to improve neurological outcome in patients after ICH. To test this
      hypothesis, the tumor necrosis factor alpha (TNF-alpha) antibody CNTO5048 was
      administered to mice after ICH induction, and histological and functional
      endpoints were assessed. METHODS: Using 10 to 12-week-old C57BL/6J male mice, ICH
      was induced by collagenase injection into the left basal ganglia. Brain TNF-alpha
      concentration, microglia activation/macrophage recruitment, hematoma volume,
      cerebral edema, and rotorod latency were assessed in mice treated with the TNF
      alpha antibody, CNTO5048, or vehicle. RESULTS: After ICH induction, mice treated
      with CNTO5048 demonstrated reduction in microglial activation/macrophage
      recruitment compared to vehicle-treated animals, as assessed by unbiased
      stereology (P = 0.049). This reduction in F4/80-positive cells was associated
      with a reduction in cleaved caspase-3 (P = 0.046) and cerebral edema (P = 0.026)
      despite similar hematoma volumes, when compared to mice treated with vehicle
      control. Treatment with CNTO5048 after ICH induction was associated with a
      reduction in functional deficit when compared to mice treated with vehicle
      control, as assessed by rotorod latencies (P = 0.024). CONCLUSIONS: Post-injury
      treatment with the TNF-alpha antibody CNTO5048 results in less neuroinflammation
      and improved functional outcomes in a murine model of ICH.

PMID- 23962091
TI  - Atomic layer deposition of platinum catalysts on nanowire surfaces for
      photoelectrochemical water reduction.
AB  - The photocathodic hydrogen evolution reaction (HER) from p-type Si nanowire (NW)
      arrays was evaluated using platinum deposited by atomic layer deposition (ALD) as
      a HER cocatalyst. ALD of Pt on the NW surface led to a highly conformal coating
      of nanoparticles with sizes ranging from 0.5 to 3 nm, allowing for precise
      control of the Pt loading in deep submonolayer quantities. The catalytic
      performance was measured using as little as 1 cycle of Pt ALD, which corresponded
      to a surface mass loading of ~10 ng/cm(2). The quantitative exploration of the
      lower limits of Pt cocatalyst loading reported here, and its application to high
      surface-area NW photoelectrodes, establish a general approach for minimizing the
      cost of precious-metal cocatalysts for efficient and affordable solar-to-fuel
      applications. 

PMID- 23962090
TI  - Influence of cartilage extracellular matrix molecules on cell phenotype and
      neocartilage formation.
AB  - Interaction between chondrocytes and the cartilage extracellular matrix (ECM) is
      essential for maintaining the cartilage's role as a low-friction and load-bearing
      tissue. In this study, we examined the influence of cartilage zone-specific ECM
      on human articular chondrocytes (HAC) in two-dimensional and three-dimensional
      (3D) environments. Two culture systems were used. SYSTEM 1: HAC were cultured on
      cell-culture plates that had been precoated with the following ECM molecules for
      7 days: decorin, biglycan, tenascin C (superficial zone), collagen type II,
      hyaluronan (HA) (middle and deep zones), and osteopontin (deep zone). Uncoated
      standard culture plates were used as controls. Expanded cells were examined for
      phenotypic changes using real-time polymerase chain reaction. In addition,
      expanded cells were placed into high-density pellet cultures for 14 days.
      Neocartilage formation was assessed via gene expression and histology
      evaluations. SYSTEM 2: HAC that were cultured on untreated plates and
      encapsulated in a 3D alginate scaffold were mixed with one of the zone-specific
      ECM molecules. Cell viability, gene expression, and histology assessments were
      conducted on 14-day-old tissues. In HAC monolayer culture, exposure to decorin,
      HA, and osteopontin increased COL2A1 and aggrecan messenger RNA (mRNA) levels
      compared with controls. Biglycan up-regulated aggrecan without a significant
      impact on COL2A1 expression; Tenascin C reduced COL2A1 expression. Neocartilage
      formed after preculture on tenascin C and collagen type II expressed higher
      COL2A1 mRNA compared with control pellets. Preculture of HAC on HA decreased both
      COL2A1 and aggrecan expression levels compared with controls, which was
      consistent with histology. Reduced proteoglycan 4 (PRG4) mRNA levels were
      observed in HAC pellets that had been precultured with biglycan and collagen type
      II. Exposing HAC to HA directly in 3D-alginate culture most effectively induced
      neocartilage formation, showing increased COL2A1 and aggrecan, and reduced COL1A1
      compared with controls. Decorin treatments increased HAC COL2A1 mRNA levels.
      These data indicate that an appropriate exposure to cartilage-specific ECM
      proteins could be used to enhance cartilage formation and to even induce the
      formation of zone-specific phenotypes to improve cartilage regeneration. 

PMID- 23962092
TI  - Synthesis of a new bis(indolyl)methane that inhibits growth and induces apoptosis
      in human prostate cancer cells.
AB  - The synthesis and the antiproliferative activity against the human breast MCF-7,
      SkBr3 and the prostate LNCaP cancer cell lines of a series of bis(indolyl)methane
      derivatives are reported. The synthesis of new compounds was first accomplished
      by the reaction of different indoles with trimethoxyacetophenone in the presence
      of catalytic amounts of hydrochloric acid. A second procedure involving the use
      of oxalic acid dihydrate [(CO2H)2.2H2O] and N-cetyl-N,N,N-trimethylammonium
      bromide in water was carried out and led to better yields. Compound 5b
      significantly reduced LNCaP prostate cancer cell viability in a dose-dependent
      manner, with an IC50 of 0.64 +/- 0.09 MUM. To determine whether the growth
      inhibition was associated with the induction of apoptosis, treated cells were
      stained using DAPI. LNCaP cells treated with 1 MUM of 5b showed the morphological
      changes characteristic of apoptosis after 24 h of incubation. 

PMID- 23962093
TI  - Long term healthcare costs of infants who survived neonatal necrotizing
      enterocolitis: a retrospective longitudinal study among infants enrolled in Texas
      Medicaid.
AB  - BACKGROUND: Infants who survive advanced necrotizing enterocolitis (NEC) at the
      time of birth are at increased risk of having poor long term physiological and
      neurodevelopmental growth. The economic implications of the long term morbidity
      in these children have not been studied to date. This paper compares the long
      term healthcare costs beyond the initial hospitalization period incurred by
      medical and surgical NEC survivors with that of matched controls without a
      diagnosis of NEC during birth hospitalization. METHODS: The longitudinal
      healthcare utilization claim files of infants born between January 2002 and
      December 2003 and enrolled in the Texas Medicaid fee-for-service program were
      used for this research. Propensity scoring was used to match infants diagnosed
      with NEC during birth hospitalization to infants without a diagnosis of NEC on
      the basis of gender, race, prematurity, extremely low birth weight status and
      presence of any major birth defects. The Medicaid paid all-inclusive healthcare
      costs for the period from 6 months to 3 years of age among children in the
      medical NEC, surgical NEC and matched control groups were evaluated
      descriptively, and in a generalized linear regression framework in order to model
      the impact of NEC over time and by birth weight. RESULTS: Two hundred fifty NEC
      survivors (73 with surgical NEC) and 2,909 matched controls were available for
      follow-up. Medical NEC infants incurred significantly higher healthcare costs
      than matched controls between 6-12 months of age (mean incremental cost = US$
      5,112 per infant). No significant difference in healthcare costs between medical
      NEC infants and matched controls was seen after 12 months. Surgical NEC survivors
      incurred healthcare costs that were consistently higher than that of matched
      controls through 36 months of age. The mean incremental healthcare costs of
      surgical NEC infants compared to matched controls between 6-12, 12-24 and 24-36
      months of age were US$ 18,274, 14,067 (p < 0.01) and 8,501 (p = 0.06) per infant
      per six month period, respectively. These incremental costs were found to vary
      between sub-groups of infants born with birth weight < 1,000g versus >= 1,000g (p
      < 0.05). CONCLUSIONS: The all-inclusive healthcare costs of surgical NEC
      survivors continued to be substantially higher than that of matched controls
      through the early childhood development period. These results can have important
      treatment and policy implications. Further research in this topic is needed.

PMID- 23962095
TI  - Room temperature electrodeposition of molybdenum sulfide for catalytic and
      photoluminescence applications.
AB  - An elegant method for the electrodeposition of MoS2 thin films using room
      temperature ionic liquids (RTIL) as an electrolyte was developed. Simple
      molecular precursors of Mo and S were added in different concentrations to tune
      the composition and deposition process. The electrodeposition of MoS2 was
      confirmed with both Raman spectroscopy and XPS. Analysis showed that the
      electrodeposited MoS2 films form a flower shape morphology with edge active sites
      that promote the hydrogen evolution reaction (HER). Furthermore, this technique
      enables selective tuning of the film thickness and demonstrates high
      photoluminescence activity with a decrease in the number of layers. 

PMID- 23962096
TI  - Influence of face mask design on bag-valve-mask ventilation performance: a
      randomized simulation study.
AB  - BACKGROUND: Different face mask designs can influence bag-valve-mask (BVM)
      ventilation performance during resuscitation. We compared a single-use, air
      cushioned face mask (AM) with a reusable silicone face mask (SM) for quality of
      BVM ventilation on a manikin simulating cardiac arrest. METHODS: Thirty-two
      physicians were recruited, and a prospective, randomized, crossover observational
      study was conducted after an American Heart Association-accredited basic life
      support provider course and standardized practice time were completed.
      Participants performed 12 cycles of BVM ventilation with both the AM and SM on a
      SmartMan lung simulator. RESULTS: Mean tidal volume was significantly higher in
      ventilations performed using the AM vs. the SM (548 +/- 159 ml vs. 439 +/- 163
      ml, P < 0.01). In addition, the proportion of low-volume ventilation was
      significantly lower with the AM than the SM [6/12 (2-11) vs. 9/12 (5-12), P =
      0.03]. Bag-valve-AM ventilation volume was not affected by the physical
      characteristics of the rescuers, except for sex. In contrast, bag-valve-SM
      ventilation volume was affected by most of the characteristics tested, including
      sex, height, weight, hand width, hand length, and grip power. CONCLUSION: The AM
      seems to be a more efficient face mask than the SM at delivering sufficient
      ventilation volumes. The performance of the AM did not seem to be associated with
      the physical characteristics of the rescuers, whereas that of the SM was affected
      by these factors. The SM may not be an appropriate face mask for performing one
      person BVM ventilation during resuscitation for rescuers who are smaller in
      stature, have a smaller hand size, or have weaker grip power.

PMID- 23962097
TI  - Socioeconomic inequities patterns of multi-morbidity in early adolescence.
AB  - BACKGROUND: Multi-morbidity such as cumulating mental health, behavioral, and
      school difficulties (consumptions of alcohol, tobacco, cannabis, and hard drugs,
      obesity, depressive symptoms, suicide attempts, involvement in violence, and low
      school performance) is common in early adolescence and can be favored by a number
      of socioeconomic factors (gender, age, nationality, family structure, parents'
      education, father' occupation, and income). This study assessed the concurrent
      roles of various socioeconomic factors in multi-morbidity defined as cumulated
      number of difficulties (CD) which has been partially documented. METHODS:
      Adolescents from middle schools in north-eastern France (N = 1,559) completed a
      questionnaire measuring socioeconomic characteristics and mental health,
      behavioral, and school difficulties. Data were analyzed using logistic regression
      models. RESULTS: Alcohol use affected 35.2% of subjects, tobacco use 11.2%,
      cannabis use 5.6%, hard drugs use 2.8%, obesity 10.6%, depressive symptoms 13.3%,
      suicide attempts 9.9%, involvement in violence 10.3%, and low school performance
      8.2%. Insufficient income and non-intact families impacted most mental health,
      behavioral, and school difficulties with adjusted odds ratios (ORa) between 1.51
      and 3.72. Being immigrant impacted illicit drugs use and low school performance
      (ORa 2.31-4.14); low parents' education depressive symptoms (1.42) and school
      performance (3.32); and manual-worker/inactive offspring low school performance
      (2.56-3.05). Multi-morbidity was very common: CD0 44.1%, CD1 30.8%, CD2-3 18.4%,
      and CD >= 4 6.7%. Insufficient income, divorced/separated parents, reconstructed
      families, and single parents played impressive roles with strong ORa gradients
      (reaching 4.86) from CD1 to CD >= 4. Being European immigrant, low parents'
      education, and low fathers' occupations had significant gender-age-adjusted odds
      ratios for CD2-3 and CD >= 4, but these became non-significant when adjusted for
      all socioeconomic factors. Older adolescents had higher risks for multi-morbidity
      which did not change when adjusting for all socioeconomic factors. CONCLUSIONS:
      Multi-morbidity including a wide range of mental health, behavioral, and school
      difficulties was common in early adolescence. Insufficient income and non-intact
      families played impressive roles. Being immigrant, low parents' education, and
      low fathers' occupations also played strong roles but these were explained by
      insufficient income and non-intact families. Prevention against multi-morbidity
      should be designed to help adolescents to solve their difficulties, especially
      among adolescents with socioeconomic difficulties.

PMID- 23962098
TI  - Woman with hemorrhagic spots on her abdomen.
AB  - Abstract Lipodissolve is a product that is composed of phosphatidylcholine and
      deoxycholate mixture, and other adjuvant. Lipodissolve injection seems to be
      performed in many countries for local fat reduction without any legal and
      scientific evidences of its safety and efficacy despite the US FDA warning.1
      Herein, we report a case with agitation and metabolic acidosis following
      lipodissolve injection. 

PMID- 23962094
TI  - Angiogenesis inhibitors in cancer therapy: mechanistic perspective on
      classification and treatment rationales.
AB  - Angiogenesis, a process of new blood vessel formation, is a prerequisite for
      tumour growth to supply the proliferating tumour with oxygen and nutrients. The
      angiogenic process may contribute to tumour progression, invasion and metastasis,
      and is generally accepted as an indicator of tumour prognosis. Therefore,
      targeting tumour angiogenesis has become of high clinical relevance. The current
      review aimed to highlight mechanistic details of anti-angiogenic therapies and
      how they relate to classification and treatment rationales. Angiogenesis
      inhibitors are classified into either direct inhibitors that target endothelial
      cells in the growing vasculature or indirect inhibitors that prevent the
      expression or block the activity of angiogenesis inducers. The latter class
      extends to include targeted therapy against oncogenes, conventional
      chemotherapeutic agents and drugs targeting other cells of the tumour micro
      environment. Angiogenesis inhibitors may be used as either monotherapy or in
      combination with other anticancer drugs. In this context, many preclinical and
      clinical studies revealed higher therapeutic effectiveness of the combined
      treatments compared with individual treatments. The proper understanding of
      synergistic treatment modalities of angiogenesis inhibitors as well as their wide
      range of cellular targets could provide effective tools for future therapies of
      many types of cancer. 

PMID- 23962099
TI  - Review of Eastern coral snake (Micrurus fulvius fulvius) exposures managed by the
      Florida Poison Information Center Network: 1998-2010.
AB  - CONTEXT: Envenomation by the Eastern coral snake is rare but may be associated
      with significant morbidity. While effective, acquisition of North American Coral
      Snake Antivenin (NACSAV) is difficult because production was discontinued for
      many years. OBJECTIVE: The purpose of this study is to characterize coral snake
      exposures in Florida and determine the effects of varying treatment paradigms on
      patient outcomes. METHODS: This study is an observational case series of cases
      received at Florida poison centers. Included cases were Eastern coral snake
      exposures occurring between January 1, 1998 and October 31, 2010. Excluded cases
      included those found to be unrelated or those not followed for at least 24 h post
      envenomation. Case comments were reviewed to obtain data. Comparisons were made
      between asymptomatic patients receiving empiric antivenom therapy (empiric group)
      and those asymptomatic patients who received antivenom upon developing signs of
      systemic envenomation (withhold group). RESULTS: Of the 553 cases identified, 387
      were included in the final analysis. According to case comments, 56.3% of
      patients had no reported systemic symptoms. Most commonly, patients were reported
      to have pain (40.6%), paresthesias (28.4%), nausea (12.7%), and emesis (11.4%).
      NACSAV was administered to 252 patients (65%). Of those patients receiving
      NACSAV, 18.25% were reported to have had an adverse reaction. Patients in the
      withhold group (n = 106) had significantly fewer minor, moderate, and major
      outcomes than patients in the empiric group (n = 134, p < 0.01). DISCUSSION:
      While patients in the withhold group had favorable outcomes compared with those
      in the empiric group, this strategy cannot be applied to all patients presenting
      asymptomatic to healthcare facilities due to study limitations. CONCLUSION:
      Further studies are needed to determine what treatment strategy is most
      appropriate for asymptomatic patients presenting to healthcare facilities.

PMID- 23962100
TI  - Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis: an etiology worth
      considering in the differential diagnosis of delirium.
AB  - BACKGROUND: Medical toxicologists are frequently consulted when young patients
      present with delirium attributed to suspected poisoning. Medical toxicologists
      should be aware of non-toxicological mimics of delirium. We describe two patients
      ultimately diagnosed with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis
      for which a toxicological consultation was requested to evaluate for neuroleptic
      malignant syndrome (NMS). CASE 1: A 21 year old male was sent from a psychiatric
      facility for new, worsening psychotic symptoms. He had autonomic instability,
      confusion, and hyper-reflexia. He was treated for NMS without improvement, and
      after an extensive workup was unrevealing, he was discharged home with
      significant cognitive dysfunction. Stored CSF later tested positive for anti
      NMDAR antibodies. CASE 2: A 27 year old female was sent from a psychiatric
      facility for a seizure and new psychiatric symptoms. She was agitated and had
      violent, alternating extremity flexion and extension along with autonomic
      instability. She was treated for NMS, rhabdomyolysis, and rabies before analysis
      of CSF demonstrated anti-NMDAR antibodies. Treatment included surgical resection
      of a suspicious ovarian cyst, steroids and IVIG, with moderate improvement.
      DISCUSSION: Autoimmune syndromes of the central nervous system result from
      receptor dysfunction after an antibody response to extracellular or intracellular
      antigens, such as subunits of the NMDA receptor. The NMDA subunits NR2b and NR2a,
      in addition to the N-terminal region of the glycine binding NR1 subunit, have
      been implicated. Typical features such as memory loss, movement disorders, and
      hallucinations reflect the density and distribution of neuronal NDMA receptors.
      As young people, particularly young women, are predominantly affected, initial
      symptoms may be attributed to encephalopathy from drug abuse or schizophrenia.
      Toxicologists may be consulted as many features mimic NMS. Serum and
      cerebrospinal fluid can be checked for anti-NMDAR antibodies as part of a
      paraneoplastic or meningioencephalitis panel. Effective treatments have been
      described and include surgical resection and immunosuppressive medications.

PMID- 23962101
TI  - Cooperative assembly of discrete stacked aggregates driven by supramolecular host
      guest complexation.
AB  - p-Sulfonatocalix[4]arene (SC4) interacts with the aromatic dye crystal violet
      (CV) to form complexes with stoichiometries ranging from SC4:CV = 1:1 up to 1:5
      both in solution and in the gas phase. While the 1:1 complex is of the inclusion
      type, as frequently observed for other guests, in the higher-order complexes the
      CV molecules interact with SC4 in a peripheral manner. The formation of such
      complexes is driven by ionic interactions established between the dye and the
      calixarene and by CV-CV stacking interactions. The application of an advanced
      fitting procedure made possible a quantitative analysis of the UV-vis data and
      allowed the determination of the stepwise binding constants. This unprecedented
      approach provides evidence that the formation of the highest-order complexes
      occurs through a cooperative mechanism. Moreover, the development of a
      quantitative analytical model enables the possibility of using this type of
      system for water-soluble sensing assays, as is also exemplified in the present
      work. 

PMID- 23962102
TI  - Intracellular and extracellular antimicrobial resistance genes in the sludge of
      livestock waste management structures.
AB  - The sludge compartment in livestock waste management structures is a potential
      hotbed for the emergence and proliferation of antimicrobial resistance among
      bacteria. Little is known about the distribution of antimicrobial resistance
      genes (ARGs) between the intracellular and extracellular DNA pools in the sludge.
      The overall objective of this study was to assess the significance of
      extracellular ARGs to the total ARGs in the sludge of livestock waste management
      structures. In this study, sludge samples were collected from four cattle manure
      storage ponds and three swine waste treatment lagoons and analyzed for genetic
      indicators of resistance. Intracellular DNA (iDNA) and extracellular DNA (eDNA)
      in the sludge were separately extracted using an optimized protocol. ARGs
      [sul(I), sul(II), tet(O), tet(Q), and tet(X)] in both the iDNA and eDNA extracts
      were quantified using quantitative polymerase chain reaction (qPCR), and
      antimicrobials, including sulfonamides and tetracyclines, were measured using
      liquid chromatography tandem mass spectrometry. Results showed that eDNA
      constituted less than 1.5% of the total DNA in sludge. All ARGs tested were
      detected in nearly all eDNA and iDNA samples. Furthermore, every gram of dry
      sludge contained from 1.7 * 10(3) to 4.2 * 10(8) copies of extracellular ARG and
      from 3.2 * 10(7) to 3.2 * 10(10) copies of intracellular ARG. Chlortetracycline
      concentrations ranged between 187 and 2674 MUg/g of sludge wet weight (ww), while
      sulfonamide concentrations were lower than 6.3 MUg/g of sludge ww. The detection
      of ARGs in eDNA extracts suggests that transformation is a potential mechanism in
      ARG proliferation in the sludge of livestock waste management structures. 

PMID- 23962104
TI  - The frequency and seasonality of influenza and other respiratory viruses in
      Tennessee: two influenza seasons of surveillance data, 2010-2012.
AB  - BACKGROUND: In 2010, the Tennessee Department of Health, in collaboration with
      the Centers for Disease Control and Prevention (CDC), expanded influenza
      surveillance in Tennessee to include other respiratory viruses. OBJECTIVES: To
      determine the prevalence and seasonality of influenza and other respiratory
      viruses during the influenza seasons of 2010-2012. METHODS: Nasal and
      nasopharangeal swabs/washings from persons with influenza-like illness were
      collected across Tennessee. Influenza and other respiratory viruses were
      identified using a molecular-based respiratory virus panel. Influenza A positives
      were subtyped using real-time PCR according to the CDC protocol. Data were
      analyzed to describe frequency and seasonality of circulating strains. RESULTS:
      Of the 933 positive specimens, 60.3% were identified as influenza viruses, 19.8%
      rhinovirus/enterovirus, 8.6% respiratory syncytial virus (RSV), 5.8%
      metapneumovirus, 3.0% adenovirus, and 2.5% parainfluenza viruses. In the 2010
      2011 season, influenza B was prominent during weeks 48-3, while influenza A(H1N1)
      was most frequently identified during weeks 4-10. Influenza A(H3N2) was present
      at lower levels during weeks 48-17. However, in the 2011-2012 season, overall
      numbers of influenza cases were reduced and influenza A (H3N2) was the most
      abundant influenza strain. The expanded surveillance for other respiratory
      viruses noted an increase in identified specimens from the first to the second
      season for adenovirus, metapneumovirus, RSV, and rhinovirus/enterovirus.
      CONCLUSIONS: This study provides data of the influenza strains in circulation in
      Tennessee. It also establishes a baseline and time of year to expect other
      respiratory viruses that will aid in detecting outbreaks of non-influenza
      respiratory viruses in Tennessee.

PMID- 23962103
TI  - Up-regulation of heparan sulfate 6-O-sulfation in idiopathic pulmonary fibrosis.
AB  - Heparan sulfate proteoglycans (HSPGs) are integral components of the lung.
      Changes in HSPGs have been documented in idiopathic pulmonary fibrosis (IPF).
      Many of the biological functions of HSPGs are mediated by heparan sulfate (HS)
      side chains, and little is understood about these side chains in the pathogenesis
      of IPF. The aims of this study were to compare HS structure between normal and
      IPF lungs and to examine how changes in HS regulate the fibrotic process. HS
      disaccharide analysis revealed that HS 6-O-sulfation was significantly increased
      in IPF lungs compared with normal lungs, concomitant with overexpression of HS 6
      O-sulfotransferases 1 and 2 (HS6ST1/2) mRNA. Immunohistochemistry revealed that
      HS6ST2 was specifically expressed in bronchial epithelial cells, including those
      lining the honeycomb cysts in IPF lungs, whereas HS6ST1 had a broad expression
      pattern. Lung fibroblasts in the fibroblastic foci of IPF lungs expressed HS6ST1,
      and overexpression of HS6ST1 mRNA was observed in primary lung fibroblasts
      isolated from IPF lungs compared with those from normal lungs. In vitro, small
      interference RNA-mediated silencing of HS6ST1 in primary normal lung fibroblasts
      resulted in reduced Smad2 expression and activation and in reduced expression of
      collagen I and alpha-smooth muscle actin after TGF-beta1 stimulation. Similar
      results were obtained in primary IPF lung fibroblasts. Furthermore, silencing of
      HS6ST1 in normal and IPF lung fibroblasts resulted in significant down-regulation
      of TbetaRIII (betaglycan). In summary, HS 6-O-sulfation is up-regulated in IPF
      with overexpression of HS6ST1 and HS6ST2, and overexpression of HS6ST1 in lung
      fibroblasts may regulate their fibrotic responses to TGF-beta1. 

PMID- 23962105
TI  - Perinatal outcomes based on the institute of medicine guidelines for weight gain
      in twin pregnancies.
AB  - OBJECTIVE: To estimate the impact of the Institute of Medicine's (IOM) weight
      gain recommendations on perinatal outcomes in twin pregnancies. METHODS: In this
      multicenter cohort study, using the 2009 IOM guidelines, we examined pregnancy
      outcomes in 570 uncomplicated diamniotic twin pregnancies. Subjects were grouped
      according to pre-pregnancy body mass index. Perinatal outcomes were assessed
      based on whether maternal weekly weight gain was less than, at, or in excess of
      the recommended IOM guidelines. RESULTS: In women with a normal pre-pregnancy
      BMI, patients whose weight gain met the IOM recommendations had a significantly
      higher mean gestational age at delivery; less prematurity and larger birth weight
      infants compared to women whose weekly weight gain was less or excess than the
      recommended IOM guidelines. Similarly, when compared with their low weight gain
      counterparts, overweight women with appropriate weight gain had improved outcomes
      including higher mean gestational age at delivery, higher birth weight infants
      and less prematurity. In obese women, the amount of pregnancy weight gain did not
      impact perinatal outcomes. CONCLUSION: Our results confirm that weekly maternal
      weight gain according to the IOM guidelines results in improved outcomes in twin
      pregnancies. Importantly, women with a normal or overweight pre-pregnancy BMI
      whose weekly weight gain was less than recommended, had increased risks of
      prematurity and lower birth weight infants. Similarly, women with a normal pre
      pregnancy BMI whose weekly weight gain was excess than recommended had increased
      risks of prematurity and lower birth weight infants.

PMID- 23962106
TI  - Long-term follow-up of coronary venous bypass graft lesions treated with a new
      generation drug-eluting stent with bioabsorbable polymer.
AB  - BACKGROUND: To date, no published data are available regarding long-term follow
      up of new generation DES implanted in coronary artery bypass graft (CABG)
      lesions. OBJECTIVES: To assess the long-term clinical outcome of patients
      receiving the new generation Biolimus A9-coated drug-eluting stent (DES) with
      biodegradable polymer in saphenous vein grafts (SVG). METHODS: Three thousand
      sixty-seven patients were included in the NOBORI 2 registry: 71 patients with a
      total of 117 lesions received at least 1 biolimus A9 DES in SVG lesions and 2,959
      patients received percutaneous coronary intervention in other lesions. Clinical
      follow-up was performed at 1, 6, and 12 months, and annually up to 3 years.
      RESULTS: Compared to the non-CABG group, patients with CABG lesions were older (P
      < 0.001), had a higher Charlson Comorbidity Index (P = 0.004), and presented more
      often with acute coronary syndrome (P = 0.02). At 3-year follow-up, cardiac death
      occurred in 9.7% versus 2.1% (P < 0.001), myocardial infarction (MI) in 8.3%
      versus 3.0% (P = 0.02), target lesion failure in 13.9% versus 6.4% (P = 0.03),
      and major adverse cardiac event in 18.1% versus 8.6% (P = 0.01). No differences
      were observed in TV-MI and TLR, nor stent thrombosis (ST) which was generally low
      in both groups (1.4% vs 0.8%, P = NS). CONCLUSION: Albeit 3-year outcomes were
      less favorable in the CABG group, the higher cardiac mortality was apparently not
      driven by ST, target vessel MI, or TLR, but is likely due to advanced disease and
      age as well as comorbidity. The low TLR rate as well as the absence of late and
      very late ST suggest that BES are safe and effective for the treatment of CABG
      lesions.

PMID- 23962107
TI  - Candida albicans, plasticity and pathogenesis.
AB  - The yeast Candida albicans has emerged as a major public health problem during
      the past two decades. The spectrum of diseases caused by this species ranges from
      vaginal infections, which affect up to 75% of the women at least once in their
      lifetime, to deep infections in hospitalized patients which lead to high
      morbidity and mortality rates. Candida albicans may also play a role in the
      persistence or worsening of some chronic inflammatory bowel diseases. Active
      research is now improving our understanding of the molecular mechanisms and
      genetic factors in the yeast and its host which influence the development of
      disease. Despite these advances and the availability of a more extensive
      therapeutic arsenal, current progress in the control of nosocomial infections due
      to Candida remains limited, mainly due to the difficulties in diagnosing these
      infections. The biologist has a key role to play in establishing a dialogue with
      the clinician in order to identify the saprophyte/pathogen transition in patients
      as early as possible. This review provides a quick synopsis of the modern
      concepts of Candida pathogenesis with some representative examples illustrating
      the specifics traits of this yeast in terms of pathogenic adaptation.

PMID- 23962109
TI  - Phantabulation: a case of visual imagery interference on visual perception.
AB  - We report the case of a 52-year old man who, following rupture of an anterior
      communicating artery aneurysm, presented with a phenomenon not previously
      described, which we have labelled "Phantabulation." Phantabulation is
      characterized by frequent and purposeful interactions with contextually
      appropriate imagined objects. We suggest that this phenomenon results from
      confusion between real and imagined objects, caused by failure to inhibit florid
      visual imagery, facilitated by cortical release mechanisms. 

PMID- 23962108
TI  - The periplasmic cavity of LacY mutant Cys154->Gly: how open is open?
AB  - The lactose permease from Escherichia coli (LacY) is a galactoside/H(+) symporter
      that catalyzes the coupled stoichiometric transport of a sugar and an H(+) across
      the cytoplasmic membrane. X-ray crystal structures of WT LacY and the
      conformationally restricted mutant Cys154->Gly exhibit an inward-facing
      conformation with a tightly sealed periplasmic side and a deep central cleft or
      cavity open to the cytoplasm. Although the crystal structures may give the
      impression that LacY is a rigid molecule, multiple converging lines of evidence
      demonstrate that galactoside binding to WT LacY induces reciprocal opening and
      closing of periplasmic and cytoplasmic cavities, respectively. By this means, the
      sugar- and H(+)-binding sites in the middle of the molecule are exposed
      alternatively to either side of the membrane. In contrast to the crystal
      structure, biochemical/biophysical studies with mutant Cys154->Gly show that the
      periplasmic side is paralyzed in an open-outward conformation. In this study, a
      rigid, funnel-shaped, maleimide-containing molecule was used to probe the
      periplasmic cavity of a pseudo-WT and the Cys154->Gly mutant by site-directed
      alkylation. The findings provide strong support for previous observations and
      indicate further that the external opening of the periplasmic cleft in the mutant
      is patent to the extent of at least 8.5 A in the absence of sugar or about half
      that of the WT cavity with bound galactoside. 

PMID- 23962110
TI  - The combination of arsenic, interferon-alpha, and zidovudine restores an
      "immunocompetent-like" cytokine expression profile in patients with adult T-cell
      leukemia lymphoma.
AB  - BACKGROUND: HTLV-I associated adult T-cell leukemia/lymphoma (ATL) carries a
      dismal prognosis due to chemo-resistance and immuno-compromised micro
      environment. The combination of zidovudine and interferon-alpha (IFN)
      significantly improved survival in ATL. Promising results were reported by adding
      arsenic trioxide to zidovudine and IFN. RESULTS: Here we assessed Th1/Th2/T(reg)
      cytokine gene expression profiles in 16 ATL patients before and 30 days after
      treatment with arsenic/IFN/zidovudine, in comparison with HTLV-I healthy carriers
      and sero-negative blood donors. ATL patients at diagnosis displayed a T(reg)/Th2
      cytokine profile with significantly elevated transcript levels of Foxp3,
      interleukin-10 (IL-10), and IL-4 and had a reduced Th1 profile evidenced by
      decreased transcript levels of interferon-gamma (IFN-gamma) and IL-2. Most
      patients (15/16) responded, with CD4+CD25+ cells significantly decreasing after
      therapy, paralleled by decreases in Foxp3 transcript. Importantly,
      arsenic/IFN/zidovudine therapy sharply diminished IL-10 transcript and serum
      levels concomittant with decrease in IL-4 and increases in IFN-gamma and IL-2
      mRNA, whether or not values were adjusted to the percentage of CD4+CD25+ cells.
      Finally, IL-10 transcript level negatively correlated with clinical response at
      Day 30. CONCLUSIONS: The observed shift from a T(reg)/Th2 phenotype before
      treatment toward a Th1 phenotype after treatment with arsenic/IFN/zidovudine may
      play an important role in restoring an immuno-competent micro-environment, which
      enhances the eradication of ATL cells and the prevention of opportunistic
      infections.

PMID- 23962111
TI  - Overtwisted, resolvable carbon nanotube yarn entanglement as strain sensors and
      rotational actuators.
AB  - Introducing twists into carbon nanotube yarns could produce hierarchical
      architectures and extend their application areas. Here, we utilized such twists
      to produce elastic strain sensors over large strain (up to 500%) and rotation
      actuators with high energy density. We show that a helical nanotube yarn can be
      overtwisted into highly entangled, macroscopically random but locally organized
      structures, consisting of mostly double-helix segments intertwined together.
      Pulling the yarn ends completely resolved the entanglement in an elastic and
      reversible way, yielding large tensile strains with linear change in electrical
      resistance. Resolving an entangled yarn and releasing its twists could
      simultaneously rotate a heavy object (30 000 times the yarn weight) for more than
      1000 cycles at high speed. The rotational actuation generated from a single
      entangled yarn produced energy densities up to 8.3 kJ/kg, and maintained similar
      capacity during repeated use. Our entangled CNT yarns represent a complex self
      assembled system with applications as large-range strain sensors and robust
      rotational actuators. 

PMID- 23962113
TI  - Substantial compositional turnover of fungal communities in an alpine ridge-to
      snowbed gradient.
AB  - The main gradient in vascular plant, bryophyte and lichen species composition in
      alpine areas, structured by the topographic gradient from wind-exposed ridges to
      snowbeds, has been extensively studied. Tolerance to environmental stress,
      resulting from wind abrasion and desiccation towards windswept ridges or reduced
      growing season due to prolonged snow cover towards snowbeds, is an important
      ecological mechanism in this gradient. The extent to which belowground fungal
      communities are structured by the same topographic gradient and the eventual
      mechanisms involved are less well known. In this study, we analysed variation in
      fungal diversity and community composition associated with roots of the
      ectomycorrhizal plant Bistorta vivipara along the ridge-to-snowbed gradient. We
      collected root samples from fifty B. vivipara plants in ten plots in an alpine
      area in central Norway. The fungal communities were analysed using 454
      pyrosequencing analyses of tag-encoded ITS1 amplicons. A distinct gradient in the
      fungal community composition was found that coincided with variation from ridge
      to snowbeds. This gradient was paralleled by change in soil content of carbon,
      nitrogen and phosphorus. A large proportion (66%) of the detected 801
      nonsingleton operational taxonomic units (OTUs) were ascomycetes, while
      basidiomycetes dominated quantitatively (i.e. with respect to number of reads).
      Numerous fungal OTUs, many with taxonomic affinity to Sebacinales, Cortinarius
      and Meliniomyces, showed distinct affinities either to ridge or to snowbed plots,
      indicating habitat specialization. The compositional turnover of fungal
      communities along the gradient was not paralleled by a gradient in species
      richness. 

PMID- 23962112
TI  - Toxoplasma gondii Syntaxin 6 is required for vesicular transport between
      endosomal-like compartments and the Golgi complex.
AB  - Apicomplexans are obligate intracellular parasites that invade the host cell in
      an active process that relies on unique secretory organelles (micronemes,
      rhoptries and dense granules) localized at the apical tip of these highly
      polarized eukaryotes. In order for the contents of these specialized organelles
      to reach their final destination, these proteins are sorted post-Golgi and it has
      been speculated that they pass through endosomal-like compartments (ELCs), where
      they undergo maturation. Here, we characterize a Toxoplasma gondii homologue of
      Syntaxin 6 (TgStx6), a well-established marker for the early endosomes and trans
      Golgi network (TGN) in diverse eukaryotes. Indeed, TgStx6 appears to have a role
      in the retrograde transport between ELCs, the TGN and the Golgi, because
      overexpression of TgStx6 results in the development of abnormally shaped
      parasites with expanded ELCs, a fragmented Golgi and a defect in inner membrane
      complex maturation. Interestingly, other organelles such as the micronemes,
      rhoptries and the apicoplast are not affected, establishing the TGN as a major
      sorting compartment where several transport pathways intersect. It therefore
      appears that Toxoplasma has retained a plant-like secretory pathway. 

PMID- 23962115
TI  - Tumor-induced osteomalacia resulting from primary cutaneous phosphaturic
      mesenchymal tumor: a case and review of the medical literature.

PMID- 23962116
TI  - Tec.

PMID- 23962117
TI  - Chemical constituents of Cyrtomium fortumei (J.) Smith.
AB  - Five known compounds, 6'-methylglucuronide-5-hydroxy-chromone (1), ethyl alpha-d
      glactopyranoside (2), neoechinulin A (3), 9,12,13-trihydroxyoctadeca-10(E),15(Z)
      dienoic acid (4) and phellopterin (5), were isolated from water extract of
      Cyrtomium fortumei (J.) Smith. Compounds 1-5 were isolated from this genus for
      the first time, and all the compounds were evaluated in vitro against a panel of
      human cancer cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assay. Among them, compounds 3 and 4 exhibited significant cytotoxic
      activities, with IC50 values of 15.2 and 18.3 MUg/mL on MGC-803 cells,
      respectively. 

PMID- 23962118
TI  - Socio-economic position and childhood multimorbidity: a study using linkage
      between the Avon Longitudinal Study of Parents and Children and the General
      Practice Research Database.
AB  - INTRODUCTION: In adults, multimorbidity is associated with social position.
      Socially disadvantaged adults typically experience more chronic illness at a
      younger age than comparable individuals who are more advantaged. The relation
      between social position and multimorbidity amongst children and adolescents has
      not been as widely studied and is less clear. METHODS: The NHS Information Centre
      (NHS IC) linked participants in the Avon Longitudinal Study of Parents and
      Children (ALSPAC) to the General Practice Research Database (GPRD).
      Multimorbidity was measured in three different ways: using a count of the number
      of drugs prescribed, a count of chronic diseases, and a person's predicted
      resource use score; the latter two measures were derived using the Johns Hopkins
      ACG system. A number of different socio-economic position variables measured as
      part of ALSPAC during pregnancy and early childhood were considered. Ordered
      logistic and negative binomial regression models were used to investigate
      associations between socio-economic variables and multimorbidity. RESULTS: After
      mutually adjusting for the different markers of socio-economic position, there
      was evidence, albeit weak, that chronic condition counts among children aged from
      0 to 9 years were higher among those whose mothers were less well educated (OR =
      0.44; 95% confidence interval 0.18-1.10; p = 0.08). Conversely, children whose
      mothers were better educated had higher rates of chronic illness between 10 and
      18 years (OR = 1.94; 95% CI 1.14-3.30). However, living in a more deprived area,
      as indicated by the Townsend score, was associated with a higher odds of chronic
      illness between 10 and 18 years (OR for each increasing decile of Townsend score
      = 1.09; 95% CI 1.00-1.19; p = 0.06). CONCLUSIONS: We have found some evidence
      that, in younger children, multimorbidity may be higher amongst children whose
      parents are less well educated. In older children and adolescents this
      association is less clear. We have also demonstrated that linkage between
      prospective observational studies and electronic patient records can provide an
      effective way of obtaining objectively measured outcome variables.

PMID- 23962119
TI  - How symbolic experience shapes children's symbolic flexibility.
AB  - The current experiments asked whether children with dual-symbolic experience
      (e.g., unimodal bilingual and bimodal) develop a preference for words like
      monolingual children (Namy & Waxman, 1998). In Experiment 1, ninety-five 18- and
      24-month-olds, with monolingual, unimodal bilingual, or bimodal symbolic
      experience, were tested in their willingness to treat digitized sounds as
      referents. In Experiment 2, forty-seven 24-month-olds, with the same types of
      symbolic experience, were tested in their willingness to treat novel words as
      referents. Monolingual children performed in ways indicative of a growing
      preference for words, whereas children with dual-symbolic experience performed in
      ways indicative of consistency in symbolic flexibility over time. Results suggest
      that the developmental trajectory of children's symbolic flexibility might depend
      on their symbolic experience. 

PMID- 23962120
TI  - Cerebral abscesses among Danish patients with hereditary haemorrhagic
      telangiectasia.
AB  - BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a dominantly
      inherited disease characterized by a wide variety of clinical manifestations,
      including pulmonary arteriovenous malformations (PAVMs), which due to paradoxical
      embolization may cause cerebral abscess. OBJECTIVE: To estimate the risk of
      cerebral abscess among patients with HHT. METHODS: All patients with HHT included
      in the Danish HHT data base, between January 1995 and October 2012, have been
      clinically evaluated for the presence of neurological symptoms and history of
      previous cerebral abscess. RESULTS: A total of 337 patients with HHT have been
      included in the Danish database. Of these, 264 were screened for the presence of
      PAVM. In 117 patients, a PAVM was diagnosed; among these, we identified nine
      patients with a history of cerebral abscess. The prevalence of cerebral abscess
      among patients with HHT and PAVM was therefore 7.8%. The patients with a history
      of cerebral abscess were genetically evaluated, and seven had ENG mutations, one
      had an ALK1 mutation, and in one case, a mutation could not be identified.
      CONCLUSION: Patients with untreated PAVM have a considerable risk of sustaining
      cerebral abscesses. A cerebral abscess may be the first symptom leading to an HHT
      diagnosis. Patients with unexplained cerebral abscess should be evaluated for HHT
      and PAVM.

PMID- 23962122
TI  - Ultraclean single, double, and triple carbon nanotube quantum dots with recessed
      Re bottom gates.
AB  - We demonstrate that ultraclean single, double, and triple quantum dots (QDs) can
      be formed reliably in a carbon nanotube (CNT) by a straightforward fabrication
      technique. The QDs are electrostatically defined in the CNT by closely spaced
      metallic bottom gates deposited in trenches in SiO2 by sputter deposition of Re.
      The carbon nanotubes are then grown by chemical vapor deposition (CVD) across the
      trenches and contacted using conventional resist-based electron beam lithography.
      Unlike in previous work, the devices exhibit reproducibly the characteristics of
      ultraclean QDs behavior even after the subsequent electron beam lithography and
      chemical processing steps. We specifically demonstrate the high quality using CNT
      devices with two narrow bottom gates and one global back gate. Tunable by the
      gate voltages, the device can be operated in four different regimes: (i) fully p
      type with ballistic transport between the outermost contacts (over a length of
      700 nm), (ii) clean n-type single QD behavior where a QD can be induced by either
      the left or the right bottom gate, (iii) n-type double QD, and (iv) triple
      bipolar QD where the middle QD has opposite doping (p-type). Our simple
      fabrication scheme opens up a route to more complex devices based on ultraclean
      CNTs, since it allows for postgrowth processing. 

PMID- 23962121
TI  - Mucin covalently bonded to microfibers improves the patency of vascular grafts.
AB  - Due to high incidence of vascular bypass procedures, an unmet need for suitable
      vessel replacements exists, especially for small-diameter (<6 mm) vascular
      grafts. Here, we developed a novel, bilayered, synthetic vascular graft of 1-mm
      diameter that consisted of a microfibrous luminal layer and a nanofibrous outer
      layer, which was tailored to possess the same mechanical property as native
      arteries. We then chemically modified the scaffold with mucin, a glycoprotein
      lubricant on the surface of epithelial tissues, by either passive adsorption or
      covalent bonding using the di-amino-poly(ethylene glycol) linker to microfibers.
      Under static and physiological flow conditions, conjugated mucin was more stable
      than adsorbed mucin on the surfaces. Mucin could slightly inhibit blood clotting,
      and mucin coating suppressed platelet adhesion on microfibrous scaffolds. In the
      rat common carotid artery anastomosis model, grafts with conjugated mucin, but
      not adsorbed mucin, exhibited excellent patency and higher cell infiltration into
      the graft walls. Mucin, which can be easily obtained from autologous sources,
      offers a novel method for improving the hemocompatibility and surface lubrication
      of vascular grafts and many other implants.

PMID- 23962124
TI  - Factor structure of the compulsive internet use scale.
AB  - An important step in Internet addiction research is to develop standardized
      instruments for assessing Internet addiction-related symptoms. The Compulsive
      Internet Use Scale (CIUS) is a promising brief questionnaire. The aim of this
      study was to examine the factor structure of a German version of the CIUS with
      confirmatory factor analysis in a general population sample. In addition, the
      best fitting structure was tested for factorial invariance across sex, age,
      education level, and weekly Internet use. We used a weighted general population
      sample (N=8,132) of 14-64 years olds spending at least 1 hour online for private
      purposes per typical working or weekend day. Findings include that a one-factor
      model was found to fit well. It was invariant across sex, age, education level,
      and weekly Internet use. The findings support the validity of the CIUS as a short
      screening instrument.

PMID- 23962125
TI  - Sharing, caring, and surveilling: an actor-partner interdependence model
      examination of Facebook relational maintenance strategies.
AB  - Abstract Relational maintenance is connected to high quality friendships.
      Friendship maintenance behaviors may occur online via social networking sites.
      This study utilized an Actor-Partner Interdependence Model to examine how
      Facebook maintenance and surveillance affect friendship quality. Bryant and
      Marmo's (2012) Facebook maintenance scale was evaluated, revealing two factors:
      sharing and caring. Facebook surveillance was also measured. For friendship
      satisfaction and liking, significant positive actor and partner effects emerged
      for caring; significant negative actor, partner, and interaction effects emerged
      for sharing; and significant positive actor effects emerged for surveillance. For
      friendship closeness, significant positive actor effects emerged for caring and
      surveillance. 

PMID- 23962126
TI  - The moderating roles of gender and age in tablet computer adoption.
AB  - This study aims to examine the relationship between perceived usefulness, ease of
      use, and enjoyment and attitude toward tablet computers, and between social
      influence and use intentions for such devices, as moderated by gender and age.
      Results from a partial least squares analysis using a sample of 482 consumers in
      South Korea showed that perceived usefulness and enjoyment have a positive effect
      on attitude toward tablets, while social influence and attitude toward tablet
      computers have a positive influence on intention to use tablets. Furthermore,
      gender and age moderated the relationship between perceived ease of use and
      attitude toward tablets.

PMID- 23962127
TI  - Memory effects in carbocation rearrangements: structural and dynamic study of the
      norborn-2-en-7-ylmethyl-X solvolysis case.
AB  - The solvolysis of two diastereomers may give the same two products, but in
      different ratios, notwithstanding the fact that the two reaction pathways share
      an apparently identical intermediate carbocation. This has been dubbed the
      "memory effect", since the initial carbocation seems to "remember" its origin
      when undergoing further evolutions through multistep rearrangements. This
      puzzling result was studied theoretically for the case of the solvolysis of
      norborn-2-en-7-ylmethyl-X systems by defining the reaction potential energy
      surface (PES) and then carrying out a dynamical study. The PES shows that upon X(
      ) loss, multiphase rearrangements concertedly yield the two stablest
      carbocations, G and L. These carbocations are connected by a transition
      structure. The carbocation intermediates proposed in the literature do not
      correspond to any stationary point. The preference for the rearrangement to G or
      L (the memory effect) is determined by structural and stereoelectronic effects:
      the competitive interaction between an empty p orbital with a sigma orbital or a
      p/pi orbital is guided by geometrical aspects present in the starting
      carbocations. The dynamical study shows that (1) G and L do not interconvert and
      (2) the evolving system can switch from one pathway to the other to different
      extents, thus determining a more or less pronounced memory loss (the leakage). 

PMID- 23962128
TI  - Palmitoylation of Galphaq determines its association with the thromboxane
      receptor in hypoxic pulmonary hypertension.
AB  - Pulmonary arterial vasoconstriction is a hallmark of persistent pulmonary
      hypertension of the newborn (PPHN). We reported increased calcium responses to
      thromboxane and selectively increased thromboxane prostanoid (TP) association
      with Galphaq in hypoxic pulmonary artery. Palmitoylation of Galphaq is important
      for efficient receptor-Galphaq-phospholipase-C interactions. TPalpha receptor is
      not itself amenable to palmitoylation. We studied the role of Galphaq
      palmitoylation in constriction of hypoxic pulmonary artery using pharmacological
      palmitoylation inhibition, the effects of hypoxia on palmitoylation, and the
      effects of site-specific cysteine substitution mutations of Galphaq on Galphaq
      membrane targeting, TPalpha association, and calcium dose-response curve to a TP
      agonist. PPHN pulmonary artery and HEK293T cells expressing TPalpha were exposed
      to irreversible palmitoylation inhibitor 2-bromopalmitate before challenge with
      TP agonist U46619. Palmitate uptake was studied in hypoxic and normoxic myocytes.
      Wild-type Galphaq and Galphaq cysteine-to-alanine mutants C9A, C10A, and C9A/C10A
      were transiently coexpressed in HEK293T cells stably expressing TPalpha. We
      examined membrane localization of Galphaq, TP receptor-Galphaq association by
      coimmunoprecipitation, and Ca(2+) responses to U46619 in hypoxic and normoxic
      cells. Galphaq palmitoylation is essential for the Ca(2+) response to TPalpha
      stimulation. Inhibition of palmitoylation reduces contractile force to
      thromboxane in PPHN but not in control pulmonary artery. Hypoxia increases
      palmitoylation of Galphaq; the hypoxic. but not the normoxic, response to
      thromboxane is palmitoylation sensitive. Palmitoylation of one N-terminal
      cysteine is required for physical association of Galphaq with the TPalpha
      receptor. Palmitoylation of both cysteines is required for Galphaq membrane
      localization and Ca(2+) mobilization. Depalmitoylation of any one Galphaq
      cysteine reduces the hypoxic response to thromboxane challenge to equal that of
      normoxic cells. 

PMID- 23962129
TI  - Sonochemical method for preparation of copper indium sulfide nanoparticles and
      their application for solar cell.
AB  - In this paper, CuInS2 (CIS) nanoparticles were synthesized successfully via a new
      copper precursor [bis(acetylacetonato)copper(II)], [Cu(acac)2]; at room
      temperature by ultrasonic method. The effect of sulfur source, solvent, and
      reaction time was investigated on product morphology and particle size. A series
      of analyses was performed to characterize the CuInS2 microsphere including X-ray
      diffraction (XRD), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM) and photoluminescence (PL) spectroscopy. CuInS2 nanoparticles
      were prepared and coated on FTO. Later, the coated FTO was sintered so that a
      compact and dense CuInS2 film was produced and measured for photovoltaic
      characteristics such as Voc, Jsc and FF. 

PMID- 23962130
TI  - The relationship between previous treatment for cervical dysplasia and preterm
      delivery in twin gestations.
AB  - OBJECTIVE: To describe the impact of previous cervical surgery on preterm birth
      prior to 34 weeks in twins. METHODS: A retrospective review of twin pregnancies
      delivered between January 1998 and December 2005 at two institutions was
      performed. Women with a prior cold knife cone (CKC), loop electrosurgical
      excision procedure (LEEP), or ablative procedure were compared to a control group
      of women who had not undergone a previous treatment for cervical dysplasia. The
      primary outcome was delivery before 34 weeks of gestation. RESULTS: A total of
      876 women met inclusion criteria. Of these, 110 (12.6%) had previous surgical
      procedures for cervical dysplasia, including CKC (n = 10), LEEP (n = 36),
      cryotherapy (n = 59) and CO2 laser treatment (n = 5). Delivery prior to 34 weeks
      was more common in women with a previous CKC compared to women with no prior
      treatment (40% versus 11.3%; odds ratio [OR], 3.6; 95% confidence interval [CI],
      1.7-8.0). Delivery prior to 34 weeks was not more common in women with a previous
      LEEP (8.3%; OR, 0.8; 95% CI, 0.3-2.3) or ablative procedure (9.4%; OR, 0.9; 95%
      CI, 0.4-1.9) in comparison to the untreated group. Adjusting for the potential
      confounders of age, tobacco use, infertility treatments and previous preterm
      birth did not change the results. CONCLUSIONS: Previous CKC is associated with
      delivery prior to 34 weeks while LEEP and ablative procedures are not. CKC should
      be carefully considered and avoided when possible in reproductive age women.

PMID- 23962131
TI  - Underutilization of percutaneous coronary intervention for ST-elevation
      myocardial infarction in medicaid patients relative to private insurance
      patients.
AB  - OBJECTIVE: To determine whether disparities in access to invasive cardiac
      procedures still exist for Medicaid patients, given how old earlier studies are
      and given changes in the interim in appropriateness guidelines. PATIENTS AND
      METHODS: A total of 5,022 Medicaid and private insurance patients in New York
      from January 1, 2008 through December 31, 2009 under age 65 with ST-elevation
      myocardial infarction (STEMI) were compared with regard to their access to
      percutaneous coronary interventions (PCI) before and after controlling for
      numerous patient characteristics and other important factors. RESULTS: Medicaid
      patients were significantly less likely to be admitted initially to a hospital
      certified to perform PCI (90.4% vs. 94.3%, P < 0.001). Also, Medicaid patients
      were found to be significantly less likely to undergo PCI than other patients
      (adjusted odds ratio [AOR] = 0.81, 95% CI 0.66, 0.98, P = 0.03). When the
      probability of each hospital performing PCI for STEMI patients was controlled
      for, Medicaid patients were still less likely to undergo PCI after controlling
      for other risk factors (AOR = 0.80, 95% CI 0.65, 0.99, P = 0.04). CONCLUSIONS:
      Medicaid STEMI patients are significantly less likely to undergo PCI within the
      same day of admission as private pay patients even after adjusting for patient
      characteristics related to receiving PCI, and the strength of this relationship
      is not diminished when controlling for whether the admitting hospital has
      approval to perform PCI or controlling for the tendency of the admitting hospital
      to treat STEMI with PCI.

PMID- 23962132
TI  - Effects of reduced sulfur compounds on Pd-catalytic hydrodechlorination of
      trichloroethylene in groundwater by cathodic H2 under electrochemically induced
      oxidizing conditions.
AB  - Reduced sulfur compounds (RSCs) poison Pd catalysts for catalytic
      hydrodechlorination of contaminants in anoxic groundwater. This study
      investigates the effects of RSCs on Pd-catalytic hydrodechlorination of
      trichloroethylene (TCE) in oxic groundwater. Water electrolysis in an undivided
      electrolytic cell is used to produce H2 for TCE hydrodechlorination under
      oxidizing conditions. TCE is efficiently hydrodechlorinated to ethane, with
      significant accumulation of H2O2 under acidic conditions. The presence of sulfide
      at concentrations less than 93.8 MUM moderately inhibits TCE hydrodechlorination
      and H2O2 production. The presence of sulfite at low concentrations (<=1 mM)
      significantly enhances TCE decay, while at high concentration (3 mM) inhibits
      initially and enhances afterward when sulfite concentration declines to less than
      1 mM. Using radical scavenging experiments and an electron spin resonance assay,
      SO3(*-), which is generated from sulfite under oxidizing conditions, is validated
      as the new reactive species contributing to the enhancement. This study reveals a
      distinct mechanism of effect of sulfite on TCE hydrodechlorination by Pd and H2
      in oxic groundwater and presents an alternative approach to increasing resistance
      of Pd to RSCs poisoning. 

PMID- 23962133
TI  - Modulation of DNA binding by gene-specific transcription factors.
AB  - The transcription of many genes, particularly in prokaryotes, is controlled by
      transcription factors whose activity can be modulated by controlling their DNA
      binding affinity. Understanding the molecular mechanisms by which DNA binding
      affinity is regulated is important, but because forming definitive conclusions
      usually requires detailed structural information in combination with data from
      extensive biophysical, biochemical, and sometimes genetic experiments, little is
      truly understood about this topic. This review describes the biological
      requirements placed upon DNA binding transcription factors and their consequent
      properties, particularly the ways that DNA binding affinity can be modulated and
      methods for its study. What is known and not known about the mechanisms
      modulating the DNA binding affinity of a number of prokaryotic transcription
      factors, including CAP and lac repressor, is provided. 

PMID- 23962134
TI  - Increased cytokine/chemokines in serum from asthmatic and non-asthmatic patients
      with viral respiratory infection.
AB  - BACKGROUND: Respiratory viral infections can induce different cytokine/chemokine
      profiles in lung tissues and have a significant influence on patients with
      asthma. There is little information about the systemic cytokine status in viral
      respiratory-infected asthmatic patients compared with non-asthmatic patients.
      OBJECTIVES: The aim of this study was to determine changes in circulating
      cytokines (IL-1beta, TNF-alpha, IL-4, IL-5) and chemokines (MCP1: monocyte
      chemoattractant protein-1 and RANTES: regulated on activation normal T cell
      expressed and secreted) in patients with an asthmatic versus a non-asthmatic
      background with respiratory syncytial virus, parainfluenza virus or adenovirus
      respiratory infection. In addition, human monocyte cultures were incubated with
      respiratory viruses to determine the cytokine/chemokine profiles.
      PATIENTS/METHODS: Patients with asthmatic (n = 34) and non-asthmatic (n = 18)
      history and respiratory infections with respiratory syncytial virus,
      parainfluenza, and adenovirus were studied. Healthy individuals with similar age
      and sex (n = 10) were used as controls. Cytokine/chemokine content in blood and
      culture supernatants was determined by ELISA. Monocytes were isolated by
      Hystopaque gradient and cocultured with each of the above-mentioned viruses.
      RESULTS: Similar increased cytokine concentrations were observed in asthmatic and
      non-asthmatic patients. However, higher concentrations of chemokines were
      observed in asthmatic patients. Virus-infected monocyte cultures showed similar
      cytokine/chemokine profiles to those observed in the patients. CONCLUSIONS:
      Circulating cytokine profiles induced by acute viral lung infection were not
      related to asthmatic status, except for chemokines that were already increased in
      the asthmatic status. Monocytes could play an important role in the increased
      circulating concentration of cytokines found during respiratory viral infections.

PMID- 23962136
TI  - Complete mitochondrial genome of Hymeniacidon sinapium (Demospongiae,
      Halichondriidae).
AB  - The complete mitochondrial genome of Hymeniacidon sinapium (Demospongiae,
      Halichondriidae) is reported here for the first time. The H. sinapium mitogenome
      is 23,435 base pairs in total length and includes 14 protein-coding gene
      sequences, small and large rRNA sequences, and 25 tRNA sequences. All genes are
      encoded on the heavy strand without overlapping genes. 

PMID- 23962137
TI  - Case study: a patient with agenesis of the corpus callosum with minimal
      associated neuropsychological impairment.
AB  - This is a case study of an 88-year-old man who presented with agenesis of the
      corpus callosum and colpocephaly. Symptomatically, he reported a sudden onset of
      mild, intermittent left hand apraxia, but denied any previous manifestations
      consistent with this type of brain malformation. The patient underwent
      neuroimaging, evaluation by neurology, and comprehensive neuropsychological
      testing to determine the nature of any other associated impairments. Test results
      indicated that he was, with a few exceptions, neuropsychologically normal. He
      performed well on tests that are highly sensitive to acquired brain dysfunction.
      His most notable deficit was failed performance in the simultaneous and
      coordinated use of both hands in using tactile and proprioceptive feedback on the
      Tactual Performance Test. This case is discussed in terms of plasticity of the
      developing brain, including compensatory mechanisms, highlighting the variability
      in clinical outcome in the context of congenital brain malformation. This case
      study illustrates the strong influence of cerebral plasticity as well as a
      possible circumscribed manifestation of interhemispheric disconnection. 

PMID- 23962135
TI  - Drivers and deterrents of facility delivery in sub-Saharan Africa: a systematic
      review.
AB  - While the most important factors associated with facility-based delivery (FBD)
      have been explored within individual countries in Africa, no systematic review
      has explored the factors associated with FBD across sub-Saharan Africa. A
      systematic search of the peer-reviewed literature was conducted to identify
      articles published in English from 1/1995-12/2011 that reported on original
      research conducted entirely or in part in sub-Saharan Africa and included a
      primary outcome variable of FBD, delivery location, or skilled birth attendance
      (SBA). Out of 1,168 citations identified, 65 met inclusion criteria. 62 of 65
      were cross-sectional, and 58 of 65 relied upon household survey data. Fewer than
      two-thirds (43) included multivariate analyses. The factors associated with
      facility delivery were categorized as maternal, social, antenatal-related,
      facility-related, and macro-level factors. Maternal factors were the most
      commonly studied. This may be a result of the overwhelming reliance on household
      survey data - where maternal sociodemographic factors are likely to be well
      represented and non-maternal factors may be less consistently and accurately
      represented. Multivariate analysis suggests that maternal education, parity /
      birth order, rural / urban residence, household wealth / socioeconomic status,
      distance to the nearest facility, and number of antenatal care visits were the
      factors most consistently associated with FBD. In conclusion, FBD is a complex
      issue that is influenced by characteristics of the pregnant woman herself, her
      immediate social circle, the community in which she lives, the facility that is
      closest to her, and context of the country in which she lives. Research to date
      has been dominated by analysis of cross-sectional household survey data. More
      research is needed that explores regional variability, examines longitudinal
      trends, and studies the impact of interventions to boost rates of facility
      delivery in sub-Saharan Africa. 

PMID- 23962138
TI  - Rutaecarpine analogues reduce lipid accumulation in adipocytes via inhibiting
      adipogenesis/lipogenesis with AMPK activation and UPR suppression.
AB  - Obesity is characterized by expansion of adipose tissue, which results from an
      increase in adipocyte number (adipogenesis) and adipocyte size (lipogenesis). A
      reversal of these processes has been suggested to be a potential antiobetic
      therapy. Rutaecarpine (Rut) and its novel analogues (R17 and R18) were identified
      to exert potent effect in reducing lipid accumulation during adipocyte
      differentiation in 3T3-L1 adipocytes with little cytotoxicity. All three
      compounds reduced lipid accumulation in a dose-dependent manner, while R17 and
      R18 exhibited much more potent inhibitory effects compared to that of Rut.
      Further studies showed that R17 suppressed both adipogenesis and lipogenesis
      during all stages of adipocyte differentiation as indicated by the reduced
      protein and mRNA levels of key regulators of adipogenesis/lipogenesis, including
      PPARgamma, C/EBPalpha, SREBP-1c, ACC, FAS, and SCD-1. We next examined the effect
      of R17 on the UPR pathway and the results showed that the UPR markers (PERK,
      eIF2alpha, IRE1alpha, and spliced XBP1 mRNA) were all significantly reduced by
      R17. Further studies revealed that R17 persistently activated AMPK during
      differentiation, suggesting that the AMPK may be an upstream mechanism for the
      effect of R17 on adipogenesis and lipogenesis via the adipogenic/lipogenic
      markers and the UPR pathway. Finally, studies in fast/refeeding mice demonstrated
      that R17 administration was able to reduce epididymal fat mass and the levels of
      plasma TG and FFA in vivo. Our results suggest that rutaecarpine analogues may
      have therapeutic potential for obesity and related metabolic disorders. The
      mechanism involves the suppression of adipogenic/lipogenic proteins and the
      suppression of the UPR pathway possibly via the AMPK. 

PMID- 23962139
TI  - Licensing the future: report on BioMed Central's public consultation on open data
      in peer-reviewed journals.
AB  - We report the outcomes of BioMed Central's public consultation on implementing
      open data-compliant licensing in peer-reviewed open access journals. Respondents
      (42) to the 2012 consultation were six to one in favor (29 in support; 5 against;
      8 abstentions) of changing our authors' default open access copyright license
      agreement, to introduce the Creative Commons CC0 public domain waiver for data
      published in BioMed Central's journals. We summarize the different questions we
      received in response to the consultation and our responses to them - matters such
      as citation, plagiarism, patient privacy, and commercial use were raised. In
      light of the support for open data in our journals we outline our plans to
      implement, in September 2013, a combined Creative Commons Attribution license for
      published articles (papers) and Creative Commons CC0 waiver for published data. 

PMID- 23962140
TI  - A new highly oxygenated pseudoguaianolide with 5-LOX inhibitory activity from
      Rudbeckia hirta L. flowers.
AB  - A new highly oxygenated pseudoguaianolide, rudbeckolide (1), was isolated from
      Rudbeckia hirta L. flowers. The structure of this terpenoid lactone was
      established on the basis of extensive 1D and 2D NMR spectroscopic analyses. The
      compound exhibited strong 5-lipoxygenase inhibitory activity (84.9% inhibition at
      10 MUg/mL) in vitro and the result provided partial evidence for the usage of the
      plant as traditional medicine.

PMID- 23962141
TI  - Wakefulness (not sleep) promotes generalization of word learning in 2.5-year-old
      children.
AB  - Sleep enhances generalization in adults, but this has not been examined in
      toddlers. This study examined the impact of napping versus wakefulness on the
      generalization of word learning in toddlers when the contextual background
      changes during learning. Thirty 2.5-year-old children (M = 32.94, SE = 0.46)
      learned labels for novel categories of objects, presented on different contextual
      backgrounds, and were tested on their ability to generalize the labels to new
      exemplars after a 4-hr delay with or without a nap. The results demonstrated that
      only children who did not nap were able to generalize learning. These findings
      have critical implications for the functions of sleep versus wakefulness in
      generalization, implicating a role for forgetting during wakefulness in
      generalization.

PMID- 23962142
TI  - Prominent follicular mucinosis with diffuse scalp alopecia resembling alopecia
      areata.
AB  - A 56-year-old Caucasian female presented with a 2-month history of alopecia. On
      examination, she had diffuse hair loss of her scalp with some discrete patches of
      nonscarring alopecia. Histopathology revealed an inflammatory nonscarring
      alopecia with prominent follicular mucinosis and findings suggestive of alopecia
      areata. The patient's alopecia completely resolved with oral prednisone. The
      histopathologic findings and clinical presentation are most consistent with a
      diagnosis of alopecia areata with follicular mucinosis, although the differential
      diagnosis is broad. As follicular mucinosis may be associated with both benign
      and malignant conditions, it is important to be cautious regarding the clinical
      diagnosis when this reaction pattern is observed histopathologically. 

PMID- 23962143
TI  - The case for fencing remains intact.
AB  - Creel et al. argue against the conservation effectiveness of fencing based on a
      population measure that ignores the importance of top predators to ecosystem
      processes. Their statistical analyses consider, first, only a subset of fenced
      reserves and, second, an incomplete examination of 'costs per lion.' Our original
      conclusions remain unaltered. 

PMID- 23962145
TI  - Baseline [(123) I]FP-CIT SPECT (DaTSCAN) severity correlates with medication use
      at 3 years in Parkinson's disease.
AB  - BACKGROUND: Presynaptic dopaminergic deficiency on dopamine transporter imaging
      supports a clinical diagnosis of Parkinson's disease and correlates with the
      severity of rigidity and bradykinesia. Baseline dopaminergic deficiency predicts
      clinical severity, but the relationship with subsequent medication use has not
      been reported. METHODS: A randomly selected cross section of 83 Parkinson's
      disease (PD) patients who had [(123) I] FP-CIT SPECT at the time of clinical
      diagnosis was identified. Dopaminergic deficiency was graded 1, 2 or 3 with
      increasing severity using visual assessment and by semiquantitative analysis of
      putamen and caudate uptake. Antiparkinson medication usage and clinical severity
      by Hoehn and Yahr were noted annually to 3 years. RESULTS: In 83 patients (66%
      male, median age 65.0 years, IQ 55.4-71.8), [(123) I]FP-CIT SPECT was grade 1 in
      20 (24%), grade 2 in 53 (64%) and grade 3 in 10 patients (12%). Dopamine
      transporter uptake ratios were inversely associated with antiparkinson medication
      usage (r = -0.26, P = 0.0201) and Hoehn Yahr stage (r = -0.32, P = 0.0029) at 3
      years from baseline, but there was considerable variation in drug usage in
      individual patients. At 3 years, patients with grade 1 scans at baseline received
      a median dose of 325 levodopa equivalent units (LEU) (interquartile range 175
      433); grade 2 scan patients 400 LEU (interquartile range 300-635); and grade 3
      scan patients 460 LEU (interquartile range 252-658). CONCLUSION: The degree of
      reduction in presynaptic dopaminergic uptake at baseline is associated with
      higher antiparkinson drug dosage at follow-up, but the wide variation means that
      the baseline FP-CIT SPECT does not reliably predict drug use in individual cases.

PMID- 23962144
TI  - Education is associated with lower levels of abdominal obesity in women with a
      non-agricultural occupation: an interaction study using China's Four Provinces
      survey.
AB  - BACKGROUND: The prevalence of obesity is increasing rapidly in low- and middle
      income countries (LMICs) as their populations become exposed to obesogenic
      environments. The transition from an agrarian to an industrial and service-based
      economy results in important lifestyle changes. Yet different socioeconomic
      groups may experience and respond to these changes differently. Investigating the
      socioeconomic distribution of obesity in LMICs is key to understanding the causes
      of obesity but the field is limited by the scarcity of data and a uni-dimensional
      approach to socioeconomic status (SES). This study splits socioeconomic status
      into two dimensions to investigate how educated women may have lower levels of
      obesity in a context where labour market opportunities have shifted away from
      agriculture to other forms of employment. METHODS: The Four Provinces Study in
      China 2008/09 is a household-based community survey of 4,314 people aged >=60 
      years (2,465 women). It was used to investigate an interaction between education
      (none/any) and occupation (agricultural/non-agricultural) on high-risk central
      obesity defined as a waist circumference >=80 cm. An interaction term between
      education and occupation was incorporated in a multivariate logistic regression
      model, and the estimates adjusted for age, parity, urban/rural residence and
      health behaviours (smoking, alcohol, meat and fruit & vegetable consumption).
      Complete case analyses were undertaken and results confirmed using multiple
      imputation to impute missing data. RESULTS: An interaction between occupation and
      education was present (P = 0.02). In the group with no education, the odds of
      central obesity in the sedentary occupation group were more than double those of
      the agricultural occupation group even after taking age group and parity into
      account (OR; 95%CI: 2.21; 1.52, 3.21), while in the group with any education
      there was no evidence of such a relationship (OR; 95%CI: 1.25; 0.92, 1.70).
      Health behaviours appeared to account for some of the association. CONCLUSION:
      These findings suggest that education may have a protective role in women against
      the higher odds of obesity associated with occupational shifts in middle-income
      countries, and that investment in women's education may present an important long
      term investment in obesity prevention. Further research could elucidate the
      mechanisms behind this association.

PMID- 23962146
TI  - Functional plasmonic nanocircuits with low insertion and propagation losses.
AB  - We experimentally demonstrate plasmonic nanocircuits operating as subdiffraction
      directional couplers optically excited with high efficiency from free-space using
      optical Yagi-Uda style antennas at lambda0 = 1550 nm. The optical Yagi-Uda style
      antennas are designed to feed channel plasmon waveguides with high efficiency
      (45% in coupling, 60% total emission), narrow angular directivity (<40 degrees ),
      and low insertion loss. SPP channel waveguides exhibit propagation lengths as
      large as 34 MUm with adiabatically tuned confinement and are integrated with
      ultracompact (5 * 10 MUm(2)), highly dispersive directional couplers, which
      enable 30 dB discrimination over Deltalambda = 200 nm with only 0.3 dB device
      loss. 

PMID- 23962147
TI  - The role of fillers and sodium metabisulfite on drug release from aged polyox
      tablets.
AB  - Polyethylene oxides (PEOs) are extensively used to control the release rate of
      drugs from matrices. Unfortunately, polyox polymers are prone to oxidation under
      high temperature and relative humidity. The aim of this study was to investigate
      the effect of sodium metabisulfite as an antioxidant to overcome the drug release
      changes from polyox matrices (PEO 301 and 303) when stored at 40  degrees C. The
      effect of different types of fillers (lactose, mannitol and dicalcium phosphate
      dihydrate) on stability of diltiazem HCl release profiles was also investigated.
      Generally, the presence of sodium metabisulfite stabilized the release of drug
      from PEO matrices stored at 40  degrees C for 8 weeks. Whilst the absence of
      metabisulfite caused an increase in drug release from polyox matrices when stored
      at 40  degrees C. The results indicate that all three concentrations (0.25, 0.5
      and 1% w/w) of sodium metabisulfite were able to overcome structural changes of
      polyox samples hence stabilizing the drug release. The results also showed that
      the incorporation of fillers in polyox matrices reduced the sensitivity of drug
      release when stored at elevated temperature. This indicates that when these
      excipients were used there was no need to incorporate additional antioxidant. DSC
      results showed that there was no difference in the melting points of fresh polyox
      samples and aged polyox samples containing sodium metabisulfite, whereas the
      melting point of aged polyox samples without sodium metabisulfite were lower than
      fresh polyox samples. This indicates that the presence of metabisulfite is
      essential to stabilize polyox samples.

PMID- 23962148
TI  - Prognostic value of serum MMP-8, -9 and TIMP-1 in patients with hepatocellular
      carcinoma.
AB  - AIM: Prediction of prognosis in hepatocellular carcinoma (HCC) is difficult. The
      aim of this study was to evaluate the prognostic value of serum MMP-8, -9, -13,
      and TIMP-1 in patients with HCC. METHODS: Pre-treatment serum samples from 134
      patients with HCC were retrospectively analyzed. The serum concentration of MMP-8
      was analyzed with immunofluorometric assay (IFMA), and those of MMP-9, MMP-13,
      and TIMP-1 were determined by enzyme-linked immunosorbent assays (ELISA).
      Clinical data were retrieved from patient records and survival data obtained from
      Statistics Finland. RESULTS: The overall cumulative disease-specific survival was
      69% at 1 year, 50% at 2 years, and 33% at 5 years. Kaplan-Meier overall survival
      analysis showed that patients with low concentrations of serum MMP-8 or TIMP-1
      had a statistically significantly better overall survival than patients with high
      concentrations of serum MMP-8 or TIMP-1 (P=0.013 and P=0.003). Interestingly, the
      overall survival in patients with high MMP-9/TIMP-1 ratio was statistically
      significantly better than in those patients with low MMP-9/TIMP-1 ratio
      (P=0.004). CONCLUSION: Our results suggest that serum MMP-8, TIMP-1, and the
      ratio of MMP-9/TIMP-1 might be useful adjuncts as predictors of prognosis in
      patients with HCC.

PMID- 23962149
TI  - Synthesis of optically active beta- or gamma-alkyl-substituted alcohols through
      copper-catalyzed asymmetric allylic alkylation with organolithium reagents.
AB  - An efficient one-pot synthesis of optically active beta-alkyl-substituted
      alcohols through a tandem copper-catalyzed asymmetric allylic alkylation (AAA)
      with organolithium reagents and reductive ozonolysis is presented. Furthermore,
      hydroboration-oxidation following the Cu-catalyzed AAA leads to the corresponding
      homochiral gamma-alkyl-substituted alcohols. 

PMID- 23962150
TI  - Double trouble: the impact of multimorbidity and deprivation on preference
      weighted health related quality of life a cross sectional analysis of the
      Scottish Health Survey.
AB  - OBJECTIVE: To investigate the association between multimorbidity and
      Preference_Weighted Health Related Quality of Life (PW_HRQoL), a score that
      combines physical and mental functioning, and how this varies by socioeconomic
      deprivation and age. DESIGN: The Scottish Health Survey (SHeS) is a cross
      sectional representative survey of the general population which included the SF
      12, a survey of HRQoL, for individuals 20 years and over. METHODS: For 7,054
      participants we generated PW_HRQoL scores by running SF-12 responses through the
      SF-6D algorithm. The resulting scores ranged from 0.29 (worst health) to 1
      (perfect health). Using ordinary least squares, we first investigated
      associations between scores and increasing counts of longstanding conditions, and
      then repeated for multimorbidity (2+ conditions). Estimates were made for the
      general population and quintiles of socioeconomic deprivation. For
      multimorbidity, the analyses were repeated stratifying the population by age
      group (20-44, 45-64, 65+). RESULTS: 45% of participants reported a longstanding
      condition and 18% reported multimorbidity. The presence of 1, 2, or 3+
      longstanding conditions were associated with average reductions in PW_HRQoL
      scores of 0.081, 0.151 and 0.212 respectively. Reduction in scores associated
      with multimorbidity was 33% greater in the most deprived quintile compared to the
      least deprived quintile, with the biggest difference (80%) in the 20-44 age
      groups. There were no significant gender differences. CONCLUSIONS: PW_HRQoL
      decreases markedly with multimorbidity, and is exacerbated by higher deprivation
      and younger age. There is a need to prioritise interventions to improve the HRQoL
      for (especially younger) adults with multimorbidity in deprived areas. BOX 1:
      What Is Known?Prevalence and premature onset of multimorbidity increases as
      socioeconomic position worsens. Previous studies have investigated the effect of
      multimorbidity on Health Related Quality of Life (HRQoL) on separate physical and
      mental health states. There is limited data on how HRQoL falls as the number of
      conditions increase, and how estimates vary across the general population.Leaving
      physical and mental health as separate categories can inhibit assessment of
      overall HRQoL. The use of a Preference_Weighted Health Related Quality of Life
      (PW_HRQoL) score provides a single summary measure of overall health, by
      weighting mental and physical states by their perceived importance as part of
      overall HRQoL. The use of a single score enables a simple and consistent
      assessment of the impact of conditions and how this varies across the population.
      Economists term PW_HRQoL scores health utilities.What this study adds?This is the
      first study to estimate how the impact of multimorbidity on PW_HRQoL scores
      varies by age group and socioeconomic deprivation. Multimorbidity has a
      substantial negative impact on HRQoL which is most severe in areas of
      deprivation, especially in younger adults.Measuring the burden of multimorbidity
      using PW_HRQoL provides consistency with how economists measure HRQoL; changes in
      which can be used in economic evaluation to assess the cost effectiveness of
      interventions.

PMID- 23962151
TI  - Distribution and uptake dynamics of mercury in leaves of common deciduous tree
      species in Minnesota, U.S.A.
AB  - A sequential extraction technique for compartmentalizing mercury (Hg) in leaves
      was developed based on a water extraction of Hg from the leaf surface followed by
      a solvent extraction of the cuticle. The bulk of leaf Hg was found in the tissue
      compartment (90-96%) with lesser amounts in the surface and cuticle compartments.
      Total leaf concentrations of Hg varied among species and was most closely
      correlated with the number of stomates per sample, supporting the hypothesis that
      stomatal uptake of atmospheric Hg (most likely Hg(0)) is a potential uptake
      pathway. Mercury concentrations in leaves were monitored from emergence to
      senescence and showed a strong positive correlation with leaf age. Leaves
      accumulated Hg throughout the growing season; the highest uptake rates coincided
      with periods of high photosynthetic activity. Concentrations of Hg in leaf tissue
      increased steadily throughout the season, but no such trends were observed for
      surficial or cuticular accumulation. Factors affecting the variability of Hg in
      leaves were analyzed to improve protocols for the potential use of leaves as
      passive monitors of atmospheric Hg. Results show that total leaf Hg
      concentrations are affected by leaf age and leaf placement in the crown. 

PMID- 23962152
TI  - The impact of psoriasis on work-related problems: a multicenter cross-sectional
      survey.
AB  - BACKGROUND: Psoriasis can have cumulative physical and psychosocial effects
      preventing sufferers from achieving their full-life potential. Few studies have
      addressed the impact of psoriasis on work-related characteristics. OBJECTIVE: To
      evaluate the impact of psoriasis on education prospects and work limitations in
      patients with moderate-to-severe psoriasis. METHODS: This study was conducted in
      29 dermatology centres across Italy. Information was collected by questionnaire
      during office visits. RESULTS: A total of 787 patients (64% male, aged 50 years)
      completed the questionnaire. At the time of the survey, mean Psoriasis Area and
      Severity Index (PASI) score and disease duration were 10 and 19 years
      respectively. Current smokers had higher PASI scores compared to non-smokers
      (10.8 vs. 9.4, P = 0.02). Plaque psoriasis was the most frequently described
      (91.2%). Fifty-five percent of patients had limited expectations of career
      progression. Similarly, in 42% of cases, psoriasis reduced the prospects of
      improvement in employment status and 35% of patients reported having reduced
      earning potential. Approximately 60% of patients reported that psoriasis
      localized to their hands or feet caused work limitations, whilst in about 25%, it
      caused them to quit their job. Approximately 37% of patients reported having lost
      between 3-10 work days in the past 3 months due to clinical assessment or
      treatment. Logistic regression revealed that gender, low standard of education,
      number of localizations, shame, anger and self-esteem were predictors
      significantly associated with limitations in work. CONCLUSIONS: Moderate-to
      severe psoriasis has a profound negative impact on the employment capacity of
      patients in Italy. Psoriasis also contributes to days lost from work, affects job
      opportunity, career prospects and revenue potential.

PMID- 23962153
TI  - The high incidence of carbapenem-resistant Klebsiella pneumoniae in urine from
      elderly hospital patients may facilitate the spread of resistant strains to the
      community.
AB  - Almost all European countries are affected by the expansion of carbapenem
      resistant Enterobacteriaceae occurring during recent years. In the two hospitals
      of Verona, Italy, the incidence of carbapenem-nonsusceptible Klebsiella
      pneumoniae (CNSKP) began to increase by the first months of 2011, reached a peak
      in the summer of the same year, and currently is around 30%. Contrary to what was
      reported by other hospitals and although significant percentages of CNSKP were
      detected in respiratory samples, blood and pus, urine from hospitalized patients,
      mainly geriatrics, are the clinical samples with the highest incidence of these
      strains. Elder patients are frequently transferred from the hospital to their own
      homes or long-term care facilities and vice-versa. Moreover, urinary tract
      infections are not considered as a severe pathology and frequently is
      asymptomatic in elderly. For these reasons, the presence of carbapenem non
      susceptible bacteria in the urinary tract of geriatric patients might be an
      underestimated cause of multiresistant strain spreading to the non-hospitalized
      population and the community. 

PMID- 23962154
TI  - Activation of PI3K/Akt/mTOR signaling pathway triggered by PTEN downregulation in
      the pathogenesis of Crohn's disease.
AB  - OBJECTIVE: We aimed to investigate the role of the phosphatidylinositol 3
      kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling
      pathway and its negative feedback factor, phosphatase and tensin homolog (PTEN),
      in the pathogenesis of Crohn's disease (CD). METHODS: Peripheral blood was
      collected from patients with CD and healthy controls while colon tissue samples
      were collected from CD patients and those complaining of constipation but with
      normal endoscopic results. CD4+ T-cells were isolated from peripheral blood. The
      expression of PI3K/Akt/mTOR pathway components and PTEN was evaluated in the
      peripheral CD4+ T-cells using polymerase chain reaction and Western blot, and in
      intestinal mucosal lymphocytes using immunohistochemistry. RESULTS: mRNA
      expressions of PI3K, Akt, mTOR, 4E-binding protein 1 (4E-BP1) and phosphate
      ribosomal protein S6 kinase (p70S6K) in peripheral CD4+ T-cells were upregulated
      in CD patients compared with healthy controls . However, the differences were not
      significant (P > 0.05). Western blot showed that the ratios of phospho-Akt: Akt,
      phosphorylated-4E-BP1: 4E-BP1 and phospho-p70S6K: p70S6K in peripheral CD4+ T
      cells were higher in CD patients (P < 0.05). The composite staining score of
      phospho-Akt and phospho-mTOR in intestinal mucosal lymphocytes also increased in
      patients with CD compared with those with constipation. Both PTEN mRNA and
      protein expressions in either peripheral CD4+ T-cells or mucosal lymphocytes were
      lower in patients with CD than in the healthy controls and those with
      constipation. CONCLUSIONS: The PI3K/Akt/mTOR signaling pathway was activated in
      CD. The activation of the PI3K/Akt/mTOR pathway caused by PTEN downregulation may
      be involved in the pathogenesis of CD.

PMID- 23962155
TI  - A case of bilateral frontal tumors without "frontal syndrome".
AB  - We report the longitudinal case study of a right-handed patient harboring two
      frontal tumors that benefited from bilateral simultaneous surgery. The tumors
      were WHO Grade II gliomas located in the left inferior frontal area (including
      the cingulate gyrus) and the right anterior superior frontal gyrus. The double
      tumor resection was guided by direct electrical stimulation of brain areas while
      the patient was awake. Neuropsychological assessments were administered before
      and after the surgery to analyse how the brain functions in the presence of two
      frontal gliomas that affect both hemispheres and reacts to a bilateral resection,
      which can brutally compromise the neuronal connectivity, progressively
      established during the infiltrating process. We showed that both the tumor
      infiltration and their bilateral resection did not lead to a "frontal syndrome"
      or a "dysexecutive syndrome" predicted by the localization models. However, a
      subtle fragility was observed in fine-grain language, memory and emotional
      skills. This case study reveals the significance of brain plasticity in the
      reorganization of cognitive networks, even in cases of bilateral tumors. It also
      confirms the clinical relevance of hodotopical brain models, which considers the
      brain to be organized in parallel-distributed networks around cortical centers
      and epicenters. 

PMID- 23962157
TI  - High immunohistochemical nestin expression is associated with greater depth of
      infiltration in dermatofibrosarcoma protuberans: a study of 71 cases.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) was recently shown to express
      nestin, a marker that has been associated with poorer prognosis when present in
      high levels in certain tumors. The objective of this study is to explore the
      association between high nestin expression and deep invasion. METHODS: We
      performed a retrospective, observational study in which we evaluated the degree
      of nestin expression in 71 DFSP. The odds of fascial involvement was calculated
      before and after adjusting for the following confounders: age, sex, tumor size,
      time to diagnosis, tumor site, the presence of fibrosarcomatous areas,
      pleomorphism, number of mitotic figures and predominant histopathologic pattern.
      We also calculated the Spearman Rho correlation coefficient between nestin
      staining intensity and depth of invasion. RESULTS: Nestin immunopositivity was
      found in 98.6% of the tumors, and high expression levels were significantly
      associated with invasion of the fascia. The odds of fascial involvement in tumors
      with strong nestin staining was 6.56 (p = 0.001) before adjustment for
      confounders and 14.86 after adjustment (p = 0.007). The Spearman rho correlation
      coefficient between nestin expression and deep invasion was 0.287 (p = 0.015).
      CONCLUSION: High inmunohistochemical nestin expression appears to be associated
      with deeper invasion in DFSP.

PMID- 23962156
TI  - Robust red FRET sensors using self-associating fluorescent domains.
AB  - Elucidation of subcellular signaling networks by multiparameter imaging is
      hindered by a lack of sensitive FRET pairs spectrally compatible with the classic
      CFP/YFP pair. Here, we present a generic strategy to enhance the traditionally
      poor sensitivity of red FRET sensors by developing self-associating variants of
      mOrange and mCherry that allow sensors to switch between well-defined on- and off
      states. Requiring just a single mutation of the mFruit domain, this new FRET pair
      improved the dynamic range of protease sensors up to 10-fold and was essential to
      generate functional red variants of CFP-YFP-based Zn(2+) sensors. The large
      dynamic range afforded by the new red FRET pair allowed simultaneous use of
      differently colored Zn(2+) FRET sensors to image Zn(2+) over a broad
      concentration range in the same cellular compartment. 

PMID- 23962158
TI  - Multilocus genetic diversity and historical biogeography of the endemic wall
      lizard from Ibiza and Formentera, Podarcis pityusensis (Squamata: Lacertidae).
AB  - Two monophyletic sister species of wall lizards inhabit the two main groups of
      Balearic Islands: Podarcis lilfordi from islets and small islands around Mallorca
      and Menorca and Podarcis pityusensis from Ibiza, Formentera and associated
      islets. Genetic diversity within the endangered P. lilfordi has been well
      characterized, but P. pityusensis has not been studied in depth. Here, 2430 bp of
      mtDNA and 15 microsatellite loci were analysed from P. pityusensis populations
      from across its natural range. Two main genetic groupings were identified,
      although geographical structuring differed slightly between the mtDNA and the
      nuclear loci. In general, individuals from islets/islands adjacent to the main
      island of Ibiza were genetically distinct from those from Formentera and the
      associated Freus islands for both mtDNA and the nuclear loci. However, most
      individuals from the island of Ibiza were grouped with neighbouring
      islets/islands for nuclear loci, but with Formentera and Freus islands for the
      mitochondrial locus. A time-calibrated Bayesian tree was constructed for the
      principal mitochondrial lineages within the Balearics, using the multispecies
      coalescent model, and provided statistical support for divergence of the two main
      P. pityusensis lineages 0.111-0.295 Ma. This suggests a mid-late Pleistocene
      intraspecific divergence, compared with an early Pleistocene divergence in P.
      lilfordi, and postdates some major increases in sea level between 0.4 and 0.6 Ma,
      which may have flooded Formentera. The program IMa2 provided a posterior
      divergence time of 0.089-0.221 Ma, which was similar to the multispecies
      coalescent tree estimate. More significantly, it indicated low but asymmetric
      effective gene copy migration rates, with higher migration from Formentera to
      Ibiza populations. Our findings suggest that much of the present-day diversity
      may have originated from a late Pleistocene colonization of one island group from
      the other, followed by allopatric divergence of these populations. Subsequent
      gene flow between these insular groups seems likely to be explained by recent
      human introductions. Two evolutionary significant units can be defined for P.
      pityusensis but these units would need to exclude the populations that have been
      the subjects of recent admixture.

PMID- 23962159
TI  - Accuracy of fetal weight estimation by ultrasound in periviable deliveries.
AB  - OBJECTIVE: To evaluate the accuracy of ultrasound estimated fetal weight (EFW)
      near viability, and to determine the adequacy of use of EFW in place of birth
      weight (BWT) for predicting prognosis for infants born near the limit of
      viability. METHODS: Retrospective chart review of women delivering between
      22(0/7) and 25(6/7) weeks gestation (GA) with ultrasound performed within 7 days
      of delivery. Potentially relevant clinical factors were evaluated regarding their
      impact on accuracy of EFW. Estimated survival based on BWT and EFW, using an
      National Institute for Child Health and Human Development (NICHD) algorithm, were
      compared. RESULTS: Study included 93 infants. Mean absolute percent difference
      (accuracy) of EFW for BWT was 9.4% (95%CI 7.4-11.3). There was no correlation
      between EFW accuracy and BWT, GA, maternal age, or BMI. There was a 3%
      overestimation of BWT per 100 g decrease in BWT (p = 0.001). Race,
      oligohydramnios, parity, smoking, or previous cesarean did not impact EFW
      accuracy. Mean predicted survival by the NICHD algorithm was 43.1% using BWT;
      43.6% using EFW (p = 0.63). An overestimation of predicted survival (using EFW
      instead of BWT) greater than 20% was detected in only two cases. CONCLUSION:
      Accuracy is similar to prior studies. Estimated newborn survival based on EFW is
      similar to that based on BWT.

PMID- 23962160
TI  - The eyes know time: a novel paradigm to reveal the development of temporal
      memory.
AB  - Temporal memory in 7-year-olds, 10-year-olds, and young adults (N = 78) was
      examined introducing a novel eye-movement paradigm. Participants learned object
      sequences and were tested under three conditions: temporal order, temporal
      context, and recognition. Age-related improvements in accuracy were found across
      conditions; accuracy in the temporal conditions was correlated with conventional
      time knowledge. Eye movements tracked the veridicality of temporal order memory
      in adults and 10-year-olds seconds before providing memory judgments, suggesting
      that these movements reflect implicit access to temporal information. Seven-year
      olds overall did not show this eye-movement effect, but those who did were more
      accurate than those who did not. Results suggest that eye movements capture
      aspects of temporal memory development that precede overt decision processes-with
      implications for hippocampal development.

PMID- 23962161
TI  - Rubrolide R: a new furanone metabolite from the ascidian Synoicum of the Indian
      Ocean.
AB  - A new furanone metabolite of the rubrolide family, rubrolide R as diacetate (1),
      was isolated from a new species of the ascidian Synoicum, besides the known
      compounds rubrolide A (as diacetate), cadiolide B and prunolide A. The structure
      of the new rubrolide was elucidated by a study of spectral data. The crude
      extract and isolated compounds (prunolide A and cadiolide B) showed antiviral
      activity against the Japanese encephalitis virus. Prunolide A showed cytotoxic
      activity against breast cancer cell lines at a concentration of < 1 MUM. 

PMID- 23962162
TI  - A qualitative study of Ottawa university students' awareness, knowledge and
      perceptions of infertility, infertility risk factors and assisted reproductive
      technologies (ART).
AB  - BACKGROUND: Awareness of infertility risk factors is an essential first step to
      safeguard future fertility. Whereas several studies have examined university
      students' awareness of female fertility and related risk factors, the topic of
      male infertility has not been well examined. The objective of this study was to
      assess young men and women's awareness, knowledge and perceptions of infertility,
      male and female infertility risk factors and assisted reproductive technologies
      (ART). METHODS: Semi-structured interviews were conducted in 2008 with a multi
      ethnic sample of sixteen male and twenty-three female Ottawa university students,
      followed by qualitative data analysis to identify major themes. Interview topics
      included awareness of male and female infertility risk factors, infertility
      diagnosis/treatments and personal options in the event of future infertility.
      RESULTS: Participants were generally familiar with infertility as a biomedical
      health problem, could identify sex-specific risk factors but overestimated
      fertility of women in their thirties and ART success rates. Reproductive health
      knowledge gaps and confusion of the physiological life-stage of menopause with
      infertility were apparent. Most participants would pursue in vitro fertilization
      or international adoption in the event of personal infertility. Some participants
      wished to use a 'natural' approach and were concerned with potential side effects
      of ART-related medications. CONCLUSIONS: The general awareness of infertility in
      young adults is promising and supports the potential uptake for health promotion
      of fertility preservation. This study underscores the continued need for
      comprehensive sexual and reproductive health education and promotion for
      adolescents and young adults.

PMID- 23962163
TI  - High-resolution screening combined with HPLC-HRMS-SPE-NMR for identification of
      potential health-promoting constituents in sea aster and searocket--new Nordic
      food ingredients.
AB  - Sea aster (Aster tripolium L.) and searocket (Cakile maritima Scop.), potential
      ingredients in the New Nordic Diet, were analyzed by high-resolution radical
      scavenging and high-resolution alpha-glucosidase inhibition assays. Results from
      the two bioactivity profiles were used to guide subsequent structural analysis
      toward constituents with potential health-promoting effects. Structural analysis
      was performed by high-performance liquid chromatography-high-resolution mass
      spectrometry-solid-phase extraction and automated tube transfer nuclear magnetic
      resonance spectroscopy, that is, HPLC-HRMS-SPE-ttNMR. High-resolution mass
      spectrometry together with detailed analysis of one- and two-dimensional proton
      detected NMR experiments enabled unambiguous assignment of the targeted analytes.
      This revealed a series of caffeoyl esters (1, 2, 5), flavonoid glycosides (3, 4,
      6, 11-15), flavonoids (7-9), sinapate esters (10, 16, 17), and sinapinic acid
      (18) associated with radical scavenging and/or alpha-glucosidase inhibition. In
      vitro assays implemented in this study showed that sea aster holds potential as a
      future functional food ingredient for lowering postprandial blood glucose level
      for diabetics, but further investigations are needed to prove the effect in vivo.

PMID- 23962164
TI  - Retraction: Does changing from a first generation antipsychotic (perphenazin) to
      a second generation antipsychotic (risperidone) alter brain activation and motor
      activity? A case report.

PMID- 23962165
TI  - Changes in Arabidopsis thaliana gene expression in response to silver
      nanoparticles and silver ions.
AB  - The release of silver nanoparticles (AgNPs) in the environment has raised
      concerns about their effects on living organisms, including plants. In this
      study, changes in gene expression in Arabidopsis thaliana exposed to
      polyvinylpyrrolidone-coated AgNPs and silver ions (Ag(+)) were analyzed using
      Affymetrix expression microarrays. Exposure to 5 mg/L AgNPs (20 nm) for 10 days
      resulted in upregulation of 286 genes and downregulation of 81 genes by reference
      to nonexposed plants. Exposure to 5 mg/L Ag(+) for 10 days resulted in
      upregulation of 84 genes and downregulation of 53 genes by reference to
      nonexposed plants. Many genes differentially expressed by AgNPs and Ag(+) were
      found to be involved in the response of plants to various stresses: upregulated
      genes were primarily associated with the response to metals and oxidative stress
      (e.g., vacuolar cation/proton exchanger, superoxide dismutase, cytochrome P450
      dependent oxidase, and peroxidase), while downregulated genes were more
      associated with response to pathogens and hormonal stimuli [e.g., auxin-regulated
      gene involved in organ size (ARGOS), ethylene signaling pathway, and systemic
      acquired resistance (SAR) against fungi and bacteria]. A significant overlap was
      observed between genes differentially expressed in response to AgNPs and Ag(+)
      (13 and 21% of total up- and downregulated genes, respectively), suggesting that
      AgNP-induced stress originates partly from silver toxicity and partly from
      nanoparticle-specific effects. Three highly upregulated genes in the presence of
      AgNPs, but not Ag(+), belong to the thalianol biosynthetic pathway, which is
      thought to be involved in the plant defense system. Results from this study
      provide insights into the molecular mechanisms of the response of plants to AgNPs
      and Ag(+). 

PMID- 23962166
TI  - Comparative characterization and cytotoxicity study of TAT-peptide as potential
      vectors for siRNA and Dicer-substrate siRNA.
AB  - Recently, a newly discovered Dicer-substrate siRNA (DsiRNA) demonstrates higher
      potency in gene silencing than siRNA but both suffer from rapid degradation, poor
      cellular uptake and chemical instability. Therefore, Tat-peptide was exploited to
      protect and facilitate their delivery into cells. In this study, Tat-peptide was
      complexed with siRNA or DsiRNA through simple complexation. The physicochemical
      properties (particle size, surface charge and morphology) of the complexes formed
      were then characterized. The ability of Tat-peptide to carry and protect siRNA or
      DsiRNA was determined by UV-Vis spectrophotometry and serum protection assay,
      respectively. Cytotoxicity effect of these complexes was assessed in V79 cell
      line. siRNA-Tat complexes had particle size ranged from 186 +/- 17.8 to 375 +/-
      8.3 nm with surface charge ranged from -9.3 +/- 1.0 to +13.5 +/- 1.0 mV,
      depending on the Tat-to-siRNA concentration ratio. As for DsiRNA-Tat complexes,
      the particle size was smaller than the ones complexed with siRNA, ranging from
      176 +/- 8.6 to 458 +/- 14.7 nm. Their surface charge was in the range of +27.1 +/
      3.6 to +38.1 +/- 0.9 mV. Both oligonucleotide (ON) species bound strongly to Tat
      peptide, forming stable complexes with loading efficiency of more than 86%. These
      complexes were relatively non cytotoxic as the cell viability of ~90% was
      achieved. In conclusion, Tat-peptide has a great potential as siRNA and DsiRNA
      vector due to the formation of stable complexes with desirable physical
      characteristics, low toxicity and able to carry high amount of siRNA or DsiRNA.

PMID- 23962167
TI  - Idiopathic pulmonary fibrosis--a systematic review on methodology for the
      collection of epidemiological data.
AB  - BACKGROUND: Recent studies suggest that the incidence of idiopathic pulmonary
      fibrosis (IPF) is rising. Accurate epidemiological data on IPF, however, are
      sparse and the results of previous studies are contradictory. This study was
      undertaken to gain insight into the various methods used in the epidemiological
      research of IPF, and to get accurate and comparable data on these different
      methodologies. METHODS: A systematic database search was performed in order to
      identify all epidemiological studies on IPF after the previous guidelines for
      diagnosis and treatment were published in 2000. Medline (via Pubmed), Science
      Sitation Index (via Web of Science) and Embase databases were searched for
      original epidemiological articles published in English in international peer
      reviewed journals starting from 2001. After pre-screening and a full-text review,
      13 articles were accepted for data abstraction. RESULTS: Three different
      methodologies of epidemiological studies were most commonly used, namely: (1)
      national registry databases, (2) questionnaire-based studies, and (3) analysis of
      the health care system's own registry databases. The overall prevalence and
      incidence of IPF varied in these studies between 0.5-27.9/100,000 and 0.22
      8.8/100,000, respectively. According to four studies the mortality and incidence
      of IPF are rising. CONCLUSIONS: We conclude that there are numerous ways to
      execute epidemiological research in the field of IPF. This review offers the
      possibility to compare the different methodologies that have been used, and this
      information could form a basis for future studies investigating the prevalence
      and incidence of IPF.

PMID- 23962168
TI  - The Escherichia coli divisome: born to divide.
AB  - Septation in Escherichia coli involves complex molecular mechanisms that
      contribute to the accuracy of bacterial division. The proto-ring, a complex made
      up by the FtsZ, FtsA and ZipA proteins, forms at the beginning of the process and
      directs the assembly of the full divisome. Central to this complex is the FtsZ
      protein, a GTPase able to assemble into a ring-like structure that responds to
      several modulatory inputs including mechanisms to position the septum at midcell.
      The connection with the cell wall synthesising machinery stabilizes the
      constriction of the cytoplasmic membrane. Although a substantial amount of
      evidence supports this description, many details on how individual divisome
      elements are structured or how they function are subjected to controversial
      interpretations. We discuss these discrepancies arising from incomplete data and
      from technical difficulties imposed by the small size of bacteria. Future work,
      including more powerful imaging and reconstruction technologies, will help to
      clarify the missing details on the architecture and function of the bacterial
      division machinery. 

PMID- 23962169
TI  - Short and long term determinants of incident multimorbidity in a cohort of 1988
      earthquake survivors in Armenia.
AB  - BACKGROUND: Multimorbidity, presence of two or more health conditions, is a
      widespread phenomenon affecting populations' health all over the world. It
      becomes a serious public health concern due to its negative consequences on
      quality of life, mortality, and cost of healthcare services utilization. Studies
      exploring determinants of multimorbidity are limited, particularly those looking
      at vulnerable populations prospectively over time. This study aimed at
      identifying short and long term socioeconomic, psychosocial, and health
      behavioral determinants of incident multimorbidity among a cohort of the 1988
      Armenian earthquake survivors. METHODS: The study included a representative
      subsample of 725 from a larger initial cohort of the earthquake survivors. Data
      on this subsample were collected via four phases of this cohort study during the
      period 1990-2012. The final logistic regression analysis eliminated all those
      cases with baseline multimorbidity to investigate short and long term
      determinants of incident multimorbidity; this subsample included 600
      participants. RESULTS: More than 75% of the studied sample had multimorbidity.
      Perceived low affordability of healthcare services, poor living standards during
      the post-earthquake decade, and lower education were independent predictors of
      incident multimorbidity developed during the period 1990-2012. Stressful life
      events and poor social support were among psychosocial determinants of incident
      multimorbidity. Participants' baseline BMI reported in 1990 was independently
      associated with incident multimorbidity. CONCLUSIONS: Most of the identified
      determinants of incident multimorbidity in our study population were markers of
      social inequities, indicating that inequities pose a serious threat to both
      individual and public health-related outcomes. Strategies targeting to decrease
      such inequities along with promotion of healthy lifestyle and strengthening of
      social networks may considerably reduce multimorbidity among population groups
      with similar socioeconomic and cultural profiles.

PMID- 23962170
TI  - Trends in incidence and predictions of cutaneous melanoma across Europe up to
      2015.
AB  - BACKGROUND: Melanoma is a significant health problem in Caucasian populations.
      The most recently available data from cancer registries often have a delay of
      several months up to a few years and they are generally not easily accessible.
      OBJECTIVES: To assess recent age- and sex-specific trends in melanoma incidence
      and make predictions for 2010 and 2015. METHODS: A retrospective registry-based
      analysis was performed with data from 29 European cancer registries. Most of them
      had data available from 1990 up to 2006/7. World-standardized incidence rates
      (WSR) and the estimated annual percentage change (EAPC) were computed.
      Predictions were based on linear projection models. RESULTS: Overall the
      incidence of melanoma is rapidly rising and will continue to do so. The incidence
      among women in Europe was generally higher than in men. The highest incidence
      rates were seen for Northern and north-western countries like the UK, Ireland and
      the Netherlands. The lowest incidence rates were observed in Portugal and Spain.
      The incidence overall remained stable in Norway, where, amongst young (25-49
      years) Norwegian males rates significantly decreased (EAPC -2.8, 95% CI -3.6; 
      2.0). Despite a low melanoma incidence among persons above the age of 70, this
      age group experienced the greatest increase in risk during the study period.
      CONCLUSIONS: Incidence rates of melanoma are expected to continue rising. These
      trends are worrying in terms of disease burden, particularly in eastern European
      countries.

PMID- 23962171
TI  - Access to the protoilludane core by gold-catalyzed allene-vinylcyclopropane
      cycloisomerization.
AB  - Gold(I)-catalyzed allene-vinylcyclopropane cycloisomerization leads to the
      tricyclic framework of the protoilludanes in a single step by a reaction that
      involves a cyclopropane ring expansion and a Prins cyclization. 

PMID- 23962172
TI  - Biofilm formation by Aspergillus fumigatus.
AB  - Aspergillus fumigatus is a well adapted, opportunistic fungus that causes a
      severe and commonly fatal disease, invasive pulmonary aspergillosis (IPA), in
      highly immunocompromised patients, aspergilloma in patients with lung cavities
      and allergic bronchopulmonary aspergillosis (ABPA) in hypersensitive individuals.
      Recent studies have suggested that biofilm formation by A. fumigatus may be one
      of the most important virulence factors in IPA and aspergilloma. Several fungal
      constituents may contribute to the formation of biofilm structures on host cells,
      including cell wall components, secondary metabolites and drug transporters. The
      biofilm phenotype of the fungus is refractory to most conventional antifungal
      treatment options. Thus, an in-depth analysis and understanding of A. fumigatus
      biofilms is necessary to devise newer and better antifungal targets for treating
      complex A. fumigatus biofilm-associated diseases. 

PMID- 23962173
TI  - A randomized controlled trial on the effectiveness of a rumination-focused group
      treatment for residual depression.
AB  - The maintenance of residual symptoms following acute treatment is common and is
      associated with poor long-term prognosis. This study investigates whether a
      cognitive-behavioral group treatment is effective in reducing residual depression
      by targeting depressive rumination. Participants (N=60) were randomly assigned to
      either the group treatment or a wait-list control condition. Treatment
      significantly improved depressed mood, rumination, perceived control over
      rumination and dysfunctional metacognitive beliefs compared with the wait
      condition. Treatment gains were maintained over the follow-up period of 1 year.
      Attrition was low and treatment satisfaction was high. Eight individuals suffered
      from a depressive relapse/recurrence in the year following treatment. The results
      indicate that cognitive-behavioral group therapy for depressive rumination is
      effective and well accepted by patients suffering from residual depression.

PMID- 23962174
TI  - Behavioral and neuroplastic effects of low-frequency rTMS of the unaffected
      hemisphere in a chronic stroke patient: a concomitant TMS and fMRI study.
AB  - Repetitive Transcranial Magnetic Stimulation (rTMS) ameliorates motor and
      neuropsychological deficits following stroke, but little is known about the
      underlying neuroplasticity. We investigated neuroplastic changes following 5 days
      of low-frequency rTMS on the intact motor cortex to promote motor recovery in a
      chronic patient with subcortical stroke. The feasibility of administering
      multiple treatments was also assessed 6 months later by applying the same
      protocol over the patient's parietal cortex to improve visuospatial disorders.
      Behavioral improvements and no adverse events were observed. Neuroimaging
      findings indicated that motor symptoms amelioration was associated with
      downregulation and cortical reorganization of hyperactive contralesional
      hemisphere. 

PMID- 23962175
TI  - Tracing type 1 diabetic Tibet miniature pig's bone marrow mesenchymal stem cells
      in vitro by magnetic resonance imaging (1).
AB  - BACKGROUND: Traditional cell-tracking methods fail to meet the needs of
      preclinical or clinical research. Thus, the aim of the present study was to
      establish a new method of double labeling bone marrow mesenchymal stem cells
      (BMSCs) from type 1 diabetic (T1D) minipigs with super-paramagnetic iron oxide
      (SPIO) and enhanced green fluorescent protein (eGFP) and tracing them using MRI
      in vitro. METHODS: Isolated BMSCs from T1D minipigs were labeled with eGFP and
      different concentrations of SPIO. The effects of lentivirus (LV)-eGFP
      transfection and SPIO on the viability and growth curves of BMSCs were determined
      by Trypan blue exclusion, the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H
      tetrazolium bromide assay and flow cytometry. Cellular ultrastructure was
      evaluated by transmission electron microscopy. Magnetic resonance imaging was
      used to evaluate BMSCs labeled with SPIO-eGFP complexes 6 weeks after labeling.
      RESULTS: Expression of eGFP in BMSCs peaked 96 h after transfection with LV-eGFP.
      Prussian blue staining revealed scattered blue granules in the cytoplasm of SPIO
      labeled cells. Transmission electron microscopy revealed that the dense granules
      aggregated mainly in secondary lysosomes. On MRI, T2* -weighted imaging was far
      more sensitive for SPIO-labeled BMSCs than other image sequences 3 and 6 weeks
      after the cells had been labeled with SPIO-eGFP. CONCLUSIONS: We have developed a
      relatively simple and safe method for double labeling of BMSCs from T1D minipigs
      using SPIO and LV-eGFP and tracing them in vitro by MRI for 6 weeks.

PMID- 23962176
TI  - Bioinspired chemistry based on minimalistic pseudopeptides.
AB  - For years researchers have tried to understand the molecular behavior of complex
      biomolecules through the development of small molecules that can partially mimic
      their function. Now researchers are implementing the reverse approach: using the
      structural and mechanistic knowledge obtained from those complex systems to
      design small molecules with defined properties and for specific applications. One
      successful strategy for constructing bioinspired, minimalistic molecules is to
      combine natural building blocks that provide functional elements with abiotic
      fragments that serve as structural scaffolds. Therefore pseudopeptidic compounds,
      most of them based on C2 symmetric structures, represent a unique opportunity to
      explore and evaluate this approach. Some of these molecules are as simple as two
      amino acids connected by a diamino spacer. The results in this Account show how
      bioinspired minimalistic pseudopeptides can form ordered structures, participate
      in the recognition and transcription of information events in molecular devices,
      and catalyze reactions. This strategy allows researchers to design and prepare a
      variety of open-chain and macrocyclic compounds leading to systems that can self
      aggregate to form hierarchically ordered micro- and nanostructures. In addition,
      small changes in the molecule or external stimuli can regulate the self
      aggregation pattern. In the same way, researchers can also tune the molecular
      movements of simple pseudopeptides through environmental factors, providing a
      means to control new molecular devices. In addition, some of the prepared model
      compounds have shown interesting properties in molecular recognition and even as
      sensors for several targets of interest. Finally we have observed remarkable
      catalytic activities from these types of molecules, although those results are
      still far from the efficiency shown by natural peptides. This family of
      pseudopeptidic compounds offers the opportunity for the more elaborate design of
      relatively simple abiotic but bioinspired systems that display specific
      properties. In addition, the results can provide additional information that will
      increase the molecular understanding of the basic principles that underlie the
      extraordinary behavior of natural systems. 

PMID- 23962177
TI  - Odon device: a promising tool to facilitate vaginal delivery and increase access
      to emergency care.
AB  - The last innovation in operative vaginal delivery happened centuries ago with the
      invention of the forceps and the vacuum extractor. The World Health Organization
      Odon Device Research Group recently published a protocol for a feasibility and
      safety study for a new device (Odon device) which aims to revolutionize assisted
      vaginal delivery. This editorial discusses the device and its pathway to global
      use. Although preliminary results look promising, the rigorous three-phased WHO
      protocol needs completion before the device can be determined, based on the
      evidence, to be safe and effective. 

PMID- 23962179
TI  - Looking into the black box: simulating the role of self-fertilization and
      mortality in the genetic structure of Macrocystis pyrifera.
AB  - Patterns of spatial genetic structure (SGS), typically estimated by genotyping
      adults, integrate migration over multiple generations and measure the effective
      gene flow of populations. SGS results can be compared with direct ecological
      studies of dispersal or mating system to gain additional insights. When
      mismatches occur, simulations can be used to illuminate the causes of these
      mismatches. Here, we report a SGS and simulation-based study of self
      fertilization in Macrocystis pyrifera, the giant kelp. We found that SGS is
      weaker than expected in M. pyrifera and used computer simulations to identify
      selfing and early mortality rates for which the individual heterozygosity
      distribution fits that of the observed data. Only one (of three) population
      showed both elevated kinship in the smallest distance class and a significant
      negative slope between kinship and geographical distance. All simulations had
      poor fit to the observed data unless mortality due to inbreeding depression was
      imposed. This mortality could only be imposed for selfing, as these were the only
      simulations to show an excess of homozygous individuals relative to the observed
      data. Thus, the expected data consistently achieved nonsignificant differences
      from the observed data only under models of selfing with mortality, with best
      fits between 32% and 42% selfing. Inbreeding depression ranged from 0.70 to 0.73.
      The results suggest that density-dependent mortality of early life stages is a
      significant force in structuring Macrocystis populations, with few highly
      homozygous individuals surviving. The success of these results should help to
      validate simulation approaches even in data-poor systems, as a means to estimate
      otherwise difficult-to-measure life cycle parameters. 

PMID- 23962178
TI  - Cytomegalovirus contributes partly to uraemia-associated premature immunological
      ageing of the T cell compartment.
AB  - Cytomegalovirus (CMV) infection has been implicated in accelerated T cell ageing.
      End-stage renal disease (ESRD) patients have a severely immunologically aged T
      cell compartment but also a high prevalence of CMV infection. We investigated
      whether CMV infection contributes to T cell ageing in ESRD patients. We
      determined the thymic output by the T cell receptor excision circle (TREC)
      content and percentage of CD31+ naive T cells. The proliferative history of the T
      cell compartment by determination of the relative telomere length (RTL) and the T
      cell differentiation status was determined by immunophenotyping. It appeared that
      CMV infection did not affect thymic output but reduced RTL of CD8+ T cells in
      ESRD patients. Moreover, increased T cell differentiation was observed with
      higher percentages of CD57+ and CD28null CD4+ and CD8+ memory T cells. These
      CD28null T cells had significantly shorter telomeres compared to CD28+ T cells.
      Therefore we concluded that CMV infection does not affect the decreased thymic
      output but increases T cell differentiation as observed in ESRD-related premature
      T cell ageing. 

PMID- 23962180
TI  - Influence of an education program of pregnant women on delivery.
AB  - OBJECTIVES: To assess whether an education program of pregnant women influences
      factors related to delivery and health behavior with newborns after delivery,
      such as the establishment of early skin-to-skin contact between the mother and
      newborn. METHODS: A multicenter observational study was carried out with
      primiparous women in four hospitals in southern Spain in 2011. Data on
      sociodemographic and obstetric variables were collected from interviews and
      clinical charts. In the analysis, crude and logistic regression adjusted odds
      ratios (ORs) were estimated. RESULTS: The study population comprised 520 women,
      354 of whom attended the education program (68.1%). The program favored the
      establishment of early skin-to-skin contact between the mother and newborn (aOR
      1.95, 95% CI 1.25-3.02, after adjusting for sociodemographic characteristics and
      the presence of pathology during pregnancy). Mothers who attended the program
      participated more actively during delivery (aOR 1.64, 95% CI 1.16-2.31). No
      association was observed between attending the program and the type of delivery
      (aOR 0.79, 95% CI 0.53-1.1) or with the frequency of cesarean section (aOR 0.81,
      95% CI 0.49-1.34). The duration of delivery was also unrelated to maternal
      education. CONCLUSIONS: Maternal education did not influence the type of
      delivery, but it favored women's participation during delivery and early skin-to
      skin contact between the mother and newborn.

PMID- 23962181
TI  - What predicts improvement of sexual function after pelvic floor surgery? A follow
      up study.
AB  - OBJECTIVE: To analyze factors predictive for changes in sexual function after
      pelvic floor surgery and explore differences between stress urinary incontinence
      (SUI) and pelvic organ prolapse (POP) surgery. DESIGN: Prospective observational
      study. SETTING: St Olav Hospital, Trondheim University Hospital, Norway. SAMPLE:
      Of 346 mailed questionnaires for women scheduled for SUI and POP surgery, 65
      questionnaires were available for analysis together with examination findings
      before and 1 year after surgery. METHODS: Postal questionnaires including
      Prolapse and Incontinence Sexual Function Questionnaire (PISQ 12), Hopkins
      Symptom Checklist 5 for psychological distress, questions from the validated Body
      Image Questionnaire, a general health question, questions addressing goals for
      improvement after surgery, clinical findings based on the Pelvic Organ Prolapse
      Quantification System and Brief Sexual Function Index for partners. Uni- and
      multivariate linear regressions adjusting for age were performed. MAIN OUTCOME
      MEASURES: Change in PISQ 12 score at follow-up. RESULTS: Sexual function
      significantly improved in the total group (p = 0.000). After stratification into
      SUI and POP surgery, improvement only remained significant after SUI surgery (p =
      0.001). Improvement for the total group was predicted by good health or coital
      incontinence, whereas psychological distress or the goal of improved defecation
      predicted deterioration. For women undergoing SUI surgery, increasing age, parity
      or the goal of improving sexuality or body image predicted improvement, while for
      women undergoing POP surgery, menopausal status or anterior colporrhaphy
      predicted improvement. CONCLUSION: Significantly improved sexuality was observed
      after pelvic floor surgery. Predictive factors for change differed for women
      undergoing SUI surgery and and those undergoing POP surgery.

PMID- 23962182
TI  - Pt-catalyzed C-C activation induced by C-H activation.
AB  - The catalytic cleavage of two C-C single bonds is achieved by treatment of the
      hydrocarbon substrate spiro[bicyclo[2.2.1]hept-2-ene-7,1'-cyclopropane] with
      Pt(II) catalysts such as (Me2bpy)PtPh(NTf2) (Me2bpy = 4,4'-dimethyl-2,2'
      bipyridine, NTf2(-) = N(SO2CF3)2(-)). The surprising rearrangement product
      1,2,4,7,7a-pentahydroindene is generated in good yield. The mechanism of C-C bond
      activation is investigated using NMR spectroscopy, electrospray ionization mass
      spectrometry, and deuterium labeling, along with density functional theory
      calculations. These studies support an unusual catalytic mechanism in which an
      initial masked C-H bond activation initiates successive C-C bond cleavage events.

PMID- 23962183
TI  - Investigation of the antimicrobial activities of Snakin-Z, a new cationic peptide
      derived from Zizyphus jujuba fruits.
AB  - Snakin-Z is a novel antimicrobial peptide (AMP) that is identified from the fruit
      of Zizyphus jujuba. This peptide is composed of 31 amino acids which is
      determined with the sequence of CARLNCVPKGTSGNTETCPCYASLHSCRKYG and molecular
      weight of 3318.82 Da. Snakin-Z is not identical to any AMP in the peptide
      database. According to this study, Snakin-Z potentially has antimicrobial
      property against bacteria and fungi. Minimal inhibitory concentration (MIC) value
      of this peptide is suitable for antimicrobial activity. We assessed that Snakin-Z
      could affect Phomopsis azadirachtae with the MIC value of 7.65 MUg/mL and vice
      versa Staphylococcus aureus with the MIC value of 28.8 MUg/mL. Interestingly,
      human red blood cells also showed good tolerance to the Snakin-Z. On the basis of
      this study, Snakin-Z can be an appropriate candidate for therapeutic applications
      in the future due to its antimicrobial property.

PMID- 23962184
TI  - Hyperammonemia induced by interaction of valproate and quetiapine.
AB  - INTRODUCTION: Hyperammonemia is one of the rare nevertheless serious side effects
      associated with valproic acid treatment. Two cases of valproic acid induced
      hyperammonemia are detailed in this article. CASES: Case one describes an adult
      male who developed hyperammonemia after acute exposure to valproic acid as a
      treatment for his bipolar disorder-manic episode. Case two developed a similar
      pattern of toxicity but after chronic exposure to valproic acid. Both patients
      were receiving a combination of valproic acid and quetiapine. DISCUSSION:
      Measurement of the ammonium level should be considered where there is a decreased
      level of consciousness in patients receiving valproic acid irrespective of the
      diagnosis and even after a long term exposure. A possible risk of hyperammonemia
      can result from a combination of valproic acid and quetiapine, however further
      studies are yet needed to confirm this hypothesis.

PMID- 23962185
TI  - An exceptional case of atrial fibrillation arrhythmia induced by etoposide.
AB  - BACKGROUND: Arrhythmia induced by etoposide is exceedingly rare. There are only a
      very few individual case histories of arrhythmias during etoposide infusion,
      including atrial fibrillation. OBJECTIVE: Through this uncommon case, we propose
      to study the pathophysiology, the diagnosis and the management of this entity.
      CASE REPORT: We report a case of a 57-year-old man, without cardiac history,
      followed for endocrine tumor of the pancreas with liver metastases who had
      presented atrial fibrillation (AF) after etoposide infusion. CONCLUSION: It is
      important to consider cardiac monitoring during etoposide infusion in patients
      with known cardiac disease or at high risk of cardiac complications.

PMID- 23962186
TI  - Probiotic approach to pathogen control in premise plumbing systems? A review.
AB  - Opportunistic pathogens occurring in premise (i.e., building) plumbing systems,
      including strains of Legionella, Mycobacterium, Acanthamoeba, and Pseudomonas,
      are now frequently cited agents of waterborne disease outbreaks. Unlike
      traditional fecal pathogens, opportunistic pathogens are part of the drinking
      water microbial ecology and therefore require new paradigms for their control.
      With the onset of the "microbiome era", notions of eradicating all microbes in
      drinking water have proven unrealistic, making a probiotic concept worthy of
      consideration. Research is needed to better understand how engineering controls
      may individually, or in combination, select for a desirable microbiome, and how
      the microbiome itself may mediate proliferation of opportunistic pathogens.
      Ecological interactions such as competition, antagonism, and obligate parasite
      host relationships offer potential targets for probiotic control of opportunistic
      pathogens. A probiotic approach may be defined as intentional inoculation of
      beneficial microbes or choosing conditions that select for a desirable
      microbiome. This critical review synthesizes the state of the knowledge of the
      factors governing opportunistic pathogen control in premise plumbing and
      potential opportunities for and barriers to implementation of a probiotic
      approach. Future effort is recommended to demonstrate the feasibility of the
      probiotic concept; to develop effective, practical, and safe protocols; and to
      engage relevant stakeholders in evaluating options and assessing corresponding
      risks. 

PMID- 23962187
TI  - Value of 3.0 T diffusion-weighted imaging in discriminating thecoma and
      fibrothecoma from other adnexal solid masses.
AB  - BACKGROUND: To investigate the value of diffusion-weighted imaging (DWI) at 3.0 T
      (3T), and especially the apparent diffusion coefficient (ADC), in discriminating
      ovarian thecoma from other adnexal solid masses. METHODS: Eighteen thecomas or
      fibrothecomas, 14 ligamentous leiomyomas, and 24 other ovarian solid tumors
      underwent prospective DWI magnetic resonance imaging (MRI) in addition to routine
      MRI on a 3T MRI machine. The baseline characteristics, components, and
      conventional MRI and DWI-MRI signals for the thecomas were recorded. The ADC
      values (ADCs) were measured for each group and compared. RESULTS: The thecomas
      often appeared as homogeneous isointensity (17/18) on T1-weighted images (T1WI;
      11/18) or T2WI (11/18) on DWI-MRI, with minor (9/18) or mild (6/18) enhancement.
      The mean ADC value for thecoma (1.20 +/- 0.45 * 10-3 mm2/s) was almost equal to
      that of the other solid ovarian masses (1.26 +/- 0.51 * 10-3 mm2/s), but lower
      than that for leiomyoma (1.48 +/- 0.42 * 10-3 mm2/s), although not significantly
      so. There was a significant difference (p = 0.043) in the ADCs of the benign
      ovarian solid masses (1.16 +/- 0.47 * 10-3 mm2/s) and leiomyomas (1.48 +/- 0.42 *
      10-3 mm2/s). CONCLUSIONS: There is no significant difference in ADC between
      thecoma and other adnexal solid masses, but the ADCs of thecomas are lower than
      those of leiomyomas.

PMID- 23962188
TI  - HPMA-LMA copolymer drug carriers in oncology: an in vivo PET study to assess the
      tumor line-specific polymer uptake and body distribution.
AB  - Polymeric drug carriers aim to selectively target tumors in combination with
      protecting normal tissue. In this regard polymer structure and molecular weight
      are key factors considering organ distribution and tumor accumulation of the
      polymeric drug delivery system. Four different HPMA based copolymer structures
      (random as well as block copolymers with lauryl methacrylate as hydrophobic
      block) varying in molecular weight, size and resulting architecture were analyzed
      in two different tumor models (AT1 prostate carcinoma and Walker-256 mammary
      carcinoma) in vivo. Polymers were labeled with (18)F and organ/tumor uptake was
      followed by MUPET imaging and ex vivo biodistribution. Vascular permeability was
      measured by dextran extravasation and vascular density by immunohistochemistry.
      Cellular polymer uptake was determined in vitro using fluorescence-labeled
      polymers. Most strikingly, the high molecular weight HPMA-LMA random copolymer
      demonstrated highest tumor uptake and blood pool concentration. The molecular
      structure (e.g., amphiphilicity) is holding a higher impact on desired in vivo
      properties than polymer size. The results also revealed pronounced differences
      between the tumor models although vascular permeability was almost comparable.
      Accumulation in Walker-256 carcinomas was much higher, presumably due to a better
      cellular uptake in this cell line and a denser vascular network in the tumors.
      These investigations clearly indicate that the properties of the individual tumor
      determine the suitability of polymeric drug carriers. The findings also
      illustrate the general necessity of a preclinical screening to analyze polymer
      uptake for each individual patient (e.g., by noninvasive PET imaging) in order to
      individualize polymer-based chemotherapy. 

PMID- 23962189
TI  - Long-term effect in ADL after an interdisciplinary rehabilitation programme for
      WAD patients: a mixed-method study for deeper understanding of participants'
      programme experiences.
AB  - PURPOSE: To evaluate long-term effects in self-perceived occupational performance
      and satisfaction in Activities of Daily Living (ADL) for patients with Whiplash
      Associated Disorders (WAD) with chronic pain in an interdisciplinary
      rehabilitation programme, and investigate patients' opinions of programme
      effects. METHOD: A mixed-method with sequential explanatory design was used.
      Fifty-three patients with WAD were followed-up 12 months after discharge. The
      Canadian Occupational Performance Measure was used to evaluate the change in ADL
      and the Multidimensional Pain Inventory for psychosocial functioning. Telephone
      interviews, based on five structured questions about the perceived impact of the
      rehabilitation programme, were made. RESULTS: The 12-month follow-up showed
      significant ADL improvement (p < 0.001). There was less interference in daily
      activities due to pain (p < 0.01), and life control increased. More people were
      back to work. Interviews revealed the programme's environment as strengthening
      and safe, and participants felt they were met with respect. Key success factors
      were to be treated with respect to being part of the social context and to obtain
      new knowledge. CONCLUSIONS: The interdisciplinary rehabilitation programme had
      initiated a process of change towards a more active life for the participants.
      They had found a new way of managing their lives. Despite the absence of pain
      reduction, they managed ADL in a better way, had more life control and returned
      to work to a higher degree. IMPLICATIONS FOR REHABILITATION: Chronic pain after
      WAD effects the entire life for many people. Long-term effects on activities of
      daily living, life control and work ability have shown positive results after an
      interdisciplinary rehabilitation programme based on behavioural and cognitive
      principles. The key success factors were to be treated with respect to being a
      part of a social context and to obtain new knowledge.

PMID- 23962190
TI  - Sensitivity and responsiveness of the health-related quality of life in stroke
      patients-40 (HRQOLISP-40) scale.
AB  - PURPOSE: To investigate the sensitivity and responsiveness of the Health-Related
      Quality of Life in Stroke Patients-40 (HRQOLISP-40) scale in evaluating stroke
      patients from onset to 12 months. METHODS: Fifty-five patients with first
      incidence stroke were followed-up for 12 months. The HRQOLISP-40 scale was used
      to assess health-related quality of life (HRQOL) while stroke severity was
      assessed with the Stroke Levity Scale. Sensitivity to change was assessed by
      analyzing changes in the HRQOLISP-40 scores between pairs of months with paired
      samples t-test. Standardized effect size (SES) and standardized response mean
      (SRM) were used to express responsiveness. RESULTS: Overall HRQOL and domains in
      the physical sphere of the HRQOLISP-40 were sensitive to change at different time
      intervals in the first 12 months post-stroke. Marked responsiveness (SES and SRM
      >0.7) was demonstrated by the overall scale, and the physical, psycho-emotional
      and cognitive domains at varying time intervals. For instance, SRM was greater
      than 0.7 between 1 and 6, 3 and 12, 1 and 9, and 1 and 12 months for both the
      physical and psycho-emotional domains. CONCLUSION: The HRQOLISP-40 is a sensitive
      and responsive stroke-specific quality of life measure that can be used to
      evaluate the outcome of stroke rehabilitation. IMPLICATIONS FOR REHABILITATION:
      Enhancing the health-related quality of life (HRQOL) of stroke survivors can be
      regarded as the ultimate goal of stroke rehabilitation. Sensitive and responsive
      stroke-specific HRQOL measures are required for use in evaluative studies, and
      clinical trials and practice. The Health-Related Quality of Life in Stroke
      Patients-40 (HRQOLISP-40) is a sensitive and responsive stroke-specific scale.

PMID- 23962191
TI  - Survival, momentum, and things that make me "me": patients' perceptions of goal
      setting after stroke.
AB  - PURPOSE: Goal setting and patient-centredness are considered fundamental concepts
      in rehabilitation. However, the best way to involve patients in setting goals
      remains unclear. The purpose of this study was to explore patient experiences of
      goal setting in post-acute stroke rehabilitation to further understanding of its
      application to practice. METHOD: Thematic analysis was used to analyse interview
      transcripts from 10 stroke survivors, recruited from 4 rehabilitation units as
      part of a pilot study investigating the effects of a structured means of
      eliciting patient-centred goals in post-acute stroke rehabilitation. RESULTS:
      Three key themes emerged: (1) "A Day by Day Momentum", comprising subordinate
      themes of "Unpredictability" and "Natural Progression" in which daily progress
      forwards was seen as an integral part of rehabilitation; (2) "Battle versus
      Alliance" in which issues of struggle versus support influenced participants'
      advancement; and (3) "The Special Things", consisting of subordinate themes of
      "What Makes Me 'Me'" and "Symbolic Achievements" concerning issues defining
      individuals and their rehabilitation experiences. CONCLUSIONS: Patients'
      discourse around goal setting can differ from the discourse conventionally used
      by clinicians when describing "best practice" in rehabilitation goal setting.
      Understanding patients' non-conventional views of goals may assist in supporting
      and motivating them, thus providing drive for their rehabilitation. IMPLICATIONS
      FOR REHABILITATION: Stroke patients think about goals very differently from
      health professionals. Individual patients have diverse ideas about goals within
      the context of the uncertainty of stroke, their life as a whole and recovery
      after formal rehabilitation is completed. To meet these diverse needs, health
      professionals need to communicate fully with patients to gain an understanding of
      their experiences of stroke and wider views on goals.

PMID- 23962192
TI  - Health-related quality of life in multiple sclerosis patients with bladder, bowel
      and sexual dysfunction.
AB  - PURPOSE: Bladder, bowel and sexual dysfunction are often overlooked symptoms in
      patients with multiple sclerosis (MS) and can be associated with lower health
      related quality of life (HRQoL). The aim is to explore the association of
      bladder, bowel and sexual dysfunction with HRQoL in MS patients stratified by
      disease duration (<=5 and >5 years) and controlled for clinical and
      sociodemographic variables. METHODS: The study comprised 223 MS patients (mean
      age 38.9 +/- 10.8 years, 67% female, mean EDSS 3.0 +/- 1.5) who filled out the
      Short-Form-36 Health Survey, the Bladder Control Scale, the Bowel Control Scale
      and the Incapacity Status Scale. The relationships between the variables were
      analyzed with multiple linear regression using the SF36's Physical Component
      Summary (PCS) and Mental Component Summary (MCS) as dependent variables. RESULTS:
      More severe bladder dysfunction was associated with lower PCS in both disease
      duration groups (beta = -0.35, p <= 0.001 versus beta = -0.43, p <= 0.001),
      whereas more severe sexual dysfunction was associated with lower MCS in the group
      with shorter disease duration (beta = -0.23, p <= 0.05). CONCLUSION: Bladder and
      sexual dysfunction are associated with a poorer HRQoL in MS patients even if they
      have had MS for a relatively short time. Recognition and proper treatment is
      needed to prevent the development of more severe dysfunction; this may also lead
      to a better HRQoL. IMPLICATIONS FOR REHABILITATION: Bladder and sexual
      dysfunction are associated with a poor health-related quality of life in MS
      patients. Sexual dysfunction may explain mental health issues among individuals
      with a short disease duration. Recognition and treatment may prevent the
      development of more severe sexual and bladder dysfunction and increase physical
      health-related quality of life.

PMID- 23962193
TI  - Disability prevalence among adults: estimates for 54 countries and progress
      toward a global estimate.
AB  - OBJECTIVES: We estimated disability prevalence among adults at global, regional
      and country levels using internationally comparable disability data and measure.
      METHODS: We conducted a retrospective analysis of data from the World Health
      Survey (WHS) (2002-2004) for nationally representative samples of civilian, non
      institutionalized populations in 54 countries. A disability was measured as
      having at least one severe or extreme difficulty with bodily functions (seeing,
      concentrating) and activities (moving around, self-care) based on an individual's
      self-reports. RESULTS: In the 54 countries under study, severe or extreme
      functional or activity difficulties are highly prevalent. For all countries,
      disability prevalence is estimated at 14% for all adults. Low and middle income
      countries have higher disability prevalence compared to high income countries.
      Among subgroups, disability prevalence stands at 12% among working age adults and
      39% among the elderly. Women have higher prevalence than men. CONCLUSIONS:
      Disability is found to be highly prevalent among adults, with an estimated global
      prevalence at 14%. Disability deserves enhanced policy attention and resources in
      public health and international development.

PMID- 23962194
TI  - Treatment components for upper limb rehabilitation after stroke: a survey of UK
      national practice.
AB  - PURPOSE: The aim of this study was to delineate the type of treatment currently
      provided to rehabilitate the upper limb following stroke in order to inform the
      treatment protocol for a control arm of a future pragmatic clinical trial of
      assistive technologies. METHOD: A national survey of stroke teams was conducted.
      Using open-ended, free script questions, the survey was designed to capture the
      important components of treatment that are most commonly used to treat patients
      described as mild, moderate or severely impaired following stroke. Stroke teams
      were targeted within the 28 geographical areas covered by the Stroke Improvement
      Networks. RESULT: Treatment descriptions were returned by 53 stroke teams from 20
      of the 28 geographical areas. In total, 998 treatment components were provided -
      289 for mildly, 403 for moderately and 306 for severely impairment patients
      following stroke). These captured five substantive treatment categories in terms
      of most active, moderately active and non-active patient participation in
      treatment as well as assistive technologies and other. CONCLUSION: From the
      treatment components described, the highest number of treatment components was
      listed for the moderately impaired patient. The treatment components used by the
      units surveyed are quite consistent with the 2012 Clinical Guidelines for Stroke.

PMID- 23962195
TI  - An exploration of alternative methods for assessing return-to-work success
      following occupational injury.
AB  - PURPOSE: To explore alternative methods for assessing return-to-work success.
      METHOD: This exploratory study employed a prospective design. Participants (N =
      150) were all vocational rehabilitation recipients who sustained a work-related
      injury that resulted in them being off work for at least 6 months, and were
      unable to return to their pre-injury position. At baseline (B), all were reported
      to have found post-injury employment. Qualitative features of the participants'
      post-injury employment were assessed at the time of initial interview (T1), which
      was conducted a mean of approximately one year following the participants'
      scheduled workplace re-entry (mean 344 days). Participants' T1 employment
      characteristics were then compared to their outcomes at the time of follow-up
      (T2), which was approximately 3 months later (mean 85 days). RESULTS: Findings
      indicate that 25% of participants were not in their baseline jobs at the time of
      last contact; some were in different jobs, however others were not working. At T1
      many of those working reported experiencing difficulties. Comparisons revealed
      significant relationships between problem indicators at T1 and employment
      outcomes at T2, with significant problem indicators including worries that
      symptoms might interfere with their ability to continue in the job, difficulties
      with the job's physical demands and a strong desire to leave their current job.
      When problem indicators were used in combination, stronger relationships were
      observed and self-assessed performance contributed to the effect. CONCLUSIONS:
      Results add support to the contention that rather than a single event, RTW is an
      evolving, complex and sometimes nonlinear process. This should be kept in mind
      when assessing the success of an injured worker's RTW.

PMID- 23962196
TI  - Making program evaluation activities family-centered: a qualitative study.
AB  - PURPOSE: This study explored ways in which program evaluation activities in
      pediatric rehabilitation settings can become congruent with family-centered
      service (FCS) philosophy. METHODS: Two Canadian pediatric rehabilitation centers
      participated in this study, which included focus groups with staff members and
      interviews with parents. RESULTS: Participants identified seven ways in which
      program evaluation practices could be made congruent with FCS. Suggestions
      included: (a) the inclusion of a diverse group of program recipients, (b) the use
      of processes that facilitate family involvement, (c) the recruitment of family
      champions, (d) the involvement of families in program development, (e) the
      establishment of evaluations that are relevant to families (f) the development of
      center-wide statements about family involvement in evaluation and (g) the
      compensation of families for their active participation in evaluation.
      CONCLUSION: For program evaluation practices to be useful and relevant, they
      should be improved and made consistent with FCS philosophy. Those evaluating
      pediatric rehabilitation programs need to use approaches and activities that
      respect the needs, characteristics, cultures and diversity of the program
      recipients. Such actions will help to improve the quality of care provided, the
      nature of program evaluation activities, as well as the overall level of FCS in
      pediatric rehabilitation settings.

PMID- 23962197
TI  - Preliminary validation study of the Spanish version of the satisfaction with life
      scale in persons with multiple sclerosis.
AB  - PURPOSE: To assess Life Satisfaction, using the Satisfaction with Life Scale
      (SWLS), and to analyze its psychometric properties in Multiple Sclerosis (MS).
      METHOD: Persons with MS (n = 84) recruited at the MS Centre of Catalonia (Spain)
      completed a battery of subjective assessments including the SWLS, the World
      Health Organization Quality of Life instrument and disability module (WHOQOL
      BREF, WHOQOL-DIS) and the Hospital Anxiety Depression Scale-Depression (HADS-D);
      sociodemographic and disability status data were also gathered. Psychometric
      properties of the SWLS were investigated using standard psychometric methods.
      RESULTS: Internal consistency (Cronbach's alpha coefficient) was 0.84. A factor
      analysis using a principal components method showed a one factor structure
      accounting for 62.6% of the variance. Statistically significant correlations were
      confirmed between SWLS with WHOQOL-BREF, WHOQOL-DIS and HADS-D. SWLS scores were
      significantly different between a priori defined groups: probable depressed
      versus nondepressed and participants perceiving a mild versus severe impact of
      disability on their lives. CONCLUSION: To the best of our knowledge, this study
      is the first to report on the psychometrics properties of the SWLS in persons
      with MS. It might be a valuable tool to use in appraising persons with MS through
      the continuum of care. IMPLICATIONS FOR REHABILITATION: The Spanish version of
      the Satisfaction with Life Scale (SWLS) is a reliable and valid instrument in
      Multiple Sclerosis (MS). The SWLS is able to discriminate between participants
      with low or high scores on depressive symptoms or disability impact on life. SWLS
      might be useful through the continuum of care in persons with MS, including
      Rehabilitation Services.

PMID- 23962198
TI  - Chitosan-containing bread made using marine shellfishery byproducts: functional,
      bioactive, and quality assessment of the end product.
AB  - Chitosan is nature's second most abundant polymer after cellulose and forms the
      structural support in crustacean shell material and Basidomycete mushroom stalks.
      Chitosan is a known antimicrobial agent but, to date, was not examined as an
      antimicrobial agent in bread formulations for the prevention of mold or rope
      formation. The aim of this work was to investigate the effects of chitosan
      generated from prawn shell byproducts on the color, moisture, and texture and
      crumb formation of bread. A secondary aim of this work was to determine the
      antimicrobial effect of chitosan added to bread at a rate of 1% against the rope
      spoilage pathogen Bacillus cereus along with natural molds. The addition of
      chitosan to bread with a molecular mass of 124000 +/- 10000 g/mol and 19%
      deacetylated was found to inhibit B. cereus growth and rope formation in bread
      when monitored over 3-5 days. Natural mold growth was also significantly delayed
      in bread made using chitosan substitution of flour at 1% compared to the control
      bread, where mold was observed growing on the bread surface after 72 h when bread
      was incubated at 30  degrees C. 

PMID- 23962199
TI  - Differences and associations of metabolic and vitamin D status among patients
      with and without sub-clinical hypothyroid dysfunction.
AB  - BACKGROUND: Sub-clinical hypothyroid dysfunction, a relatively understudied
      disorder in the Kingdom of Saudi Arabia (KSA), has significant clinical
      implications if not properly monitored. Also from KSA, more than 50% of the
      population suffer from hypovitaminosis D (<50 nmol/l). In this cross-sectional
      case-control study, we described the differences and associations in the
      metabolic patterns of adult Saudis with and without hypothyroid dysfunction in
      relation to their vitamin D status, PTH, calcium and lipid profile. METHODS: A
      total of 94 consenting adult Saudis [52 controls (without subclinical
      hypothyroidism), 42 cases (previously diagnosed subjects)] were included in this
      cross-sectional study. Anthropometrics were obtained and fasting blood samples
      were taken for ascertaining lipid and thyroid profile, as well as measuring PTH,
      25(OH) vitamin D and calcium. RESULTS: Cases had a significantly higher body mass
      index than the controls (p < 0.001). Circulating triglycerides was also
      significantly higher in cases than the controls (p = 0.001). A significant
      positive association between HDL-cholesterol and PTH (R = 0.56; p = 0.001), as
      well as a negative and modestly significant negative association between LDL
      cholesterol and PTH (R = - 20.0; p = 0.04) were observed. FT3 was inversely
      associated with circulating 25 (OH) vitamin D (R = -0.25; p = 0.01). CONCLUSIONS:
      Patients with hypothyroid dysfunction possess several cardiometabolic risk
      factors that include obesity and dyslipidemia. The association between PTH and
      cholesterol levels as well as the inverse association between vitamin D status
      and FT3 needs to be reassessed prospectively on a larger scale to confirm these
      findings.

PMID- 23962200
TI  - Dynamics and the free-energy landscape of proteins, explored with the Mossbauer
      effect and quasi-elastic neutron scattering.
AB  - The Mossbauer effect and quasi-elastic neutron scattering (QENS) from hydrated
      proteins yield sharp elastic lines that are accompanied by broad wings.
      Conventionally, the elastic line and the broad wings are treated as separate
      phenomena. We show that there is no separation; the entire spectrum consists of
      Lorentzians with the natural line width. In protein crystals, the shifts of the
      individual lines from the elastic center above about 150 K are caused by beta
      fluctuations in the hydration shell. Vibrations cause shifts in the entire
      temperature range but are best seen below about 150 K. We construct a microscopic
      model for the dynamics that is based on a random walk of the proteins in their
      free-energy landscape. The model yields approximate values for the steps in the
      energy landscape. Remarkably, the quantum electrodynamic concept of gamma rays is
      needed to justify the model. 

PMID- 23962201
TI  - The influence of socio-economic status and multimorbidity patterns on healthcare
      costs: a six-year follow-up under a universal healthcare system.
AB  - INTRODUCTION: Multimorbidity has been linked to elevated healthcare utilization
      and previous studies have found that socioeconomic status is an important factor
      associated with multimorbidity. Nonetheless, little is known regarding the impact
      of multimorbidity and socioeconomic status on healthcare costs and whether
      inequities in healthcare exist between socioeconomic classes within a universal
      healthcare system. METHODS: This longitudinal study employed the claims database
      of the National Health Insurance of Taiwan (959 990 enrolees), adopting
      medication-based Rx-defined morbidity groups (Rx-MG) as a measurement of
      multimorbidity. Mixed linear models were used to estimate the effects of
      multimorbidity and socioeconomic characteristics on annual healthcare costs
      between 2005 and 2010. RESULTS: The distribution of Rx-MGs and total costs
      presented statistically significant differences among gender, age groups,
      occupation, and income class (p < .001). Nearly 80% of the enrolees were
      classified as multimorbid and low income earners presented the highest prevalence
      of multimorbidity. After controlling for age and gender, increases in the number
      of Rx-MG assignments were associated with higher total healthcare costs. After
      controlling for the effects of Rx-MG assignment and demographic characteristics,
      physicians, paramedical personnel, and public servant were found to generate
      higher total costs than typical employees/self-employed enrolees, while low
      income earners generated lower costs. High income levels were also found to be
      associated with lower total costs. It was also revealed that occupation and
      multimorbidity have a moderating effect on healthcare cost. CONCLUSIONS:
      Increases in the prevalence of multimorbidity are associated with higher health
      care costs. This study determined that instances of multimorbidity varied
      according to socioeconomic class; likewise there were inequities in healthcare
      utilization among individuals of various occupations and income levels, even when
      demographic characteristics and multimorbidity were controlled for. This
      highlights the importance of socioeconomic status with regard to healthcare
      utilization. These results indicate that socioeconomic factors should not be
      discounted when discussing the utilization of healthcare by patients with
      multimorbidity.

PMID- 23962202
TI  - Oxidative stability and sensory evaluation of microencapsulated flaxseed oil.
AB  - Cold pressed flaxseed oil was microencapsulated by spray drying using an emulsion
      containing modified starch. The fatty acid composition, moisture, water activity,
      wettability, water holding capacity, water solubility, crystallinity, and
      particle size distribution of the microcapsules were determined. The stability of
      the microcapsules and the crude oil were assessed. An acceptance test was used
      for the sensory evaluation of a powdered supplement containing the microcapsules.
      The fatty acid composition was not significantly affected by the
      microencapsulation. The moisture, water activity, wettability, water solubility
      and crystallinity were appropriate for dry powders. The microcapsules had no
      cracks and showed better oxidative stability compared with the crude oil. Storage
      under vacuum prevented oxidation of the microcapsules. In sensory evaluation, all
      quality scores of the supplement containing microcapsules were mid-range or
      higher. The microencapsulation improved the oxidative stability of the oil and
      this procedure was satisfactorily applied in powdered food.

PMID- 23962203
TI  - Host signature effect on plant root-associated microbiomes revealed through
      analyses of resident vs. active communities.
AB  - Plant roots create specific microbial habitat in the soil - the rhizosphere. In
      this study, we characterized the rhizosphere microbiome of four host plant
      species to get insight into the impact of the host (host signature effect) on
      resident vs. active communities. Results show a distinct plant host specific
      signature found among wheat, maize, tomato and cucumber, based on the following
      three parameters: (i) each plant promoted the activity of a unique suite of soil
      bacterial populations; (ii) significant variations were observed in the number
      and the degree of dominance of active populations; and (iii) the level of
      contribution of active (rRNA-based) populations to the resident (DNA-based)
      community profiles. In the rhizoplane of all four plants, a significant reduction
      of diversity was observed, relative to the bulk soil. Moreover, an increase in
      DNA-RNA correspondence indicated higher representation of active bacterial
      populations in the residing rhizoplane community. This study demonstrates that
      the host plant determines the bacterial community composition in its immediate
      vicinity, especially with respect to the active populations. 

PMID- 23962204
TI  - Early in-session cognitive-emotional problem-solving predicts 12-month outcomes
      in depression with personality disorder.
AB  - Therapist-patient verbalizations reveal complex cognitive-emotional linguistic
      data. How these variables contribute to change requires further research.
      Emotional-cognitive text analysis using the Ulm cycles model software was applied
      to transcripts of the third session of psychotherapy for 20 patients with
      depression and personality disorder. Results showed that connecting cycle
      sequences of problem-solving in the third hour predicted 12-month clinical
      outcomes. Therapist-patient dyads most improved spent significantly more time
      early in session in connecting cycles, whilst the least improved moved into
      connecting cycles late in session. For this particular sample, it was clear that
      positive emotional problem-solving in therapy was beneficial.

PMID- 23962205
TI  - High dose benzodiazepines prolong reaction times in chronic users who have major
      depressive and/or anxiety disorders.
AB  - AIM: Short term administration of benzodiazepines (BZD) was found to prolong
      reaction time (RT) in experimental studies. However, studies on long term BZD use
      did not always adjust for important confounders and showed inconsistent results.
      We aimed to identify a possible relationship between long term BZD use and RT in
      BZD users in this large cross-sectional, observational study. METHODS: The RTs of
      non-users (n = 2404) were compared with low (n = 288), intermediate (n = 74), and
      high dose BZD users (n = 57) in the Netherlands Study of Depression and Anxiety
      (NESDA). RTs were obtained from the Implicit Association Test. Analyses were
      adjusted for sociodemographic characteristics, health indicators, severity of
      psychopathology and antidepressant use. RESULTS: Of the NESDA participants, 419
      subjects (14.8%) used BZDs. A higher dose of BZDs was associated with prolonged
      RTs (P = 0.01). When comparing the different dose groups, the high dose group,
      but not the low and medium dose groups, had significantly longer RTs than the non
      users. CONCLUSIONS: Tolerance for the RT prolonging effect of relatively high
      doses of BZDs does not seem to develop. As prolonged RTs can have adverse
      consequences in daily life, BZDs should be prescribed conservatively at the
      lowest possible dose.

PMID- 23962206
TI  - Meeting the occupational needs of a neurologically impaired client for driving: a
      case review.
AB  - Driving as a means of community mobility is an activity highly valued by
      individuals. When a medical condition impacts a person's ability to drive,
      occupational therapy practitioners should address this instrumental task of daily
      living with the client in order for the client to know if and when return to
      driving might be possible. This case review illustrates how the task of driving
      motivated a neurologically impaired client in therapy as well as how driving
      evaluation and driving rehabilitation intervention should not be done in
      isolation, but with the communication that will optimally assist the client to
      return to functional performance.

PMID- 23962207
TI  - The effect of MC1R variants and sunscreen on the response of human melanocytes in
      vivo to ultraviolet radiation and implications for melanoma.
AB  - We conducted a clinical trial to compare the molecular and cellular responses of
      human melanocytes and keratinocytes in vivo to solar-simulated ultraviolet
      radiation (SSUVR) in 57 Caucasian participants grouped according to MC1R
      genotype. We found that, on average, the density of epidermal melanocytes 14 days
      after exposure to 2 minimal erythemal dose (MED) SSUVR was twofold higher than
      baseline (unirradiated) skin. However, the change in epidermal melanocyte counts
      among people carrying germline MC1R variants (97% increase) was significantly
      less than those with wild-type MC1R (164% increase; P = 0.01). We also found that
      sunscreen applied to the skin before exposure to 2 MED SSUVR completely blocked
      the effects of DNA damage, p53 induction, and cellular proliferation in both
      melanocytes and keratinocytes. 

PMID- 23962208
TI  - Investigation on "Excimer" Formation Mechanism of Linear Oligofluorenes
      Functionalized Anthracenes by Using Transient Absorption Spectroscopy.
AB  - We study the photophysical characters of two oligofluorenes-functionalized
      anthracenes molecules with different fluorine-vinylene (FV) units, which exhibits
      that "excimer" state appears in the solution after photoexcitation. The dynamic
      data shows that two mechanisms are responsible for the generation of "excimer".
      The fast one is controlled by the arene-arene interaction between molecules and
      the slow one is influenced by the diffusion motion of molecules. Increasing the
      number of FV units may suppress the DM-dependent "excimer" and enhance the yield
      of intrinsic fluorescence, which finally improves the fluorescence property of
      molecules in solution.

PMID- 23962210
TI  - Genomic selection: Status in different species and challenges for breeding.
AB  - Technical advances and development in the market for genomic tools have
      facilitated access to whole-genome data across species. Building-up on the
      acquired knowledge of the genome sequences, large-scale genotyping has been
      optimized for broad use, so genotype information can be routinely used to predict
      genetic merit. Genomic selection (GS) refers to the use of aggregates of
      estimated marker effects as predictors which allow improved individual
      differentiation at young age. Realizable benefits of GS are influenced by several
      factors and vary in quantity and quality between species. General characteristics
      and challenges of GS in implementation and routine application are described,
      followed by an overview over the current status of its use, prospects and
      challenges in important animal species. Genetic gain for a particular trait can
      be enhanced by shortening of the generation interval, increased selection
      accuracy and increased selection intensity, with species- and breed-specific
      relevance of the determinants. Reliable predictions based on genetic marker
      effects require assembly of a reference for linking of phenotype and genotype
      data to allow estimation and regular re-estimation. Experiences from dairy
      breeding have shown that international collaboration can set the course for fast
      and successful implementation of innovative selection tools, so genomics may
      significantly impact the structures of future breeding and breeding programmes.
      Traits of great and increasing importance, which were difficult to improve in the
      conventional systems, could be emphasized, if continuous availability of high
      quality phenotype data can be assured. Equally elaborate strategies for
      genotyping and phenotyping will allow tailored approaches to balance efficient
      animal production, sustainability, animal health and welfare in future. 

PMID- 23962211
TI  - Fluorescence technologies for evaluating male gamete (dys)function.
AB  - For many years, andrologists have sought ways of assessing sperm fertility,
      especially of new sires entering the breeding chain. As knowledge of the complex
      processes that enable sperm to fertilize eggs has increased, it has become
      clearer that quantitative estimation of the fertilizing potential of a sire or an
      ejaculate is actually unlikely ever to be fully realized. Here, we propose that a
      better approach is to identify substandard males and semen samples. During the
      past decades, the use of fluorescence technologies in biomedical science has
      burgeoned, with the development of very powerful instrumentation such as confocal
      microscopy and flow cytometers of ever-increasing capabilities together with a
      vast range of fluorochromes and fluorochrome conjugates. This technology has been
      applied to andrology but thus far in only a relatively simple way. In this
      review, we offer strategies for assessing a large range of sperm functions
      thought to be related to fertilizing ability over a temporal window rather than
      at a single time point. From such an assessment profile, sperm samples that over
      respond or do not respond sufficiently could be identified, termed dysfunctional
      and rejected. We outline the rationales behind such tests, present information on
      new potentially useful fluorochromes and current flow cytometer models that would
      be suitable for the multicolour multifunctional tests we propose, and we offer
      suggestions as to how andrologists might design such multicolour tests for
      themselves. 

PMID- 23962212
TI  - Growth and regression in bovine corpora lutea: regulation by local survival and
      death pathways.
AB  - The bovine corpus luteum (CL) is a transient gland with a life span of only 18
      days in the cyclic cow. Mechanisms controlling CL development and secretory
      function may involve factors produced both within and outside this gland.
      Although luteinizing hormone (LH) surge is the main trigger of ovulation and
      granulosa cells luteinization, many locally produced agents such as arachidonic
      acid (AA) metabolites, growth factors and cytokines were shown to complement
      gonadotropins action in the process of CL development. Bovine CL is a highly
      vascular gland, where the very rapid angiogenesis rate (until Day 5 of the cycle)
      results in the development of a capillary network, endowing this gland with one
      of the highest blood flow rate per unit mass in the body. Angiogenesis in the
      developing CL is later followed by either controlled regression of the
      microvascular tree in the non-fertile cycle or maintenance and stabilization of
      the blood vessels, as seen during pregnancy. Different luteal cell types (both
      steroidogenic and accessory luteal cells: immune cells, endothelial cells,
      pericytes and fibroblasts) are involved in the pro- and/or anti-angiogenic
      responses. The balance between pro- and anti-angiogenic responses to the main
      luteolysin - prostaglandin F2alpha (PGF2alpha) could be decisive in whether or
      not PGF2alpha induces CL regression. Fibroblast growth factor-2 (FGF2) may be one
      of the factors that modulate the angiogenic response to PGF2alpha. Manipulation
      of local production and action of FGF2 will provide new tools for reproductive
      management of dairy cattle. Luteolysis is characterized by a rapid decrease in
      progesterone production, followed by structural regression. Factors like
      endothelin-1, cytokines (tumour necrosis factoralpha, interferons) and nitric
      oxide were all shown to play critical roles in functional and structural
      regression of the CL by inhibiting steroidogenesis and inducting apoptosis.

PMID- 23962213
TI  - Maturation environment and impact on subsequent developmental competence of
      bovine oocytes.
AB  - In vitro production (IVP) of bovine embryos has been improved immensely
      throughout the last decades. Nevertheless, embryos generated in vitro still
      differ from their in vivo-produced counterparts. It is possible to achieve
      blastocyst rates of up to 70% if in vivo-matured oocytes are used. In contrast,
      if oocytes are matured in vitro, blastocyst rates are only half that of those
      matured in vivo. This rather limited success may be attributed to the
      heterogeneous population of oocytes which are normally retrieved from follicles
      of 3-8 mm rather than from preovulatory follicles. In contrast to the in vivo
      ovulated oocyte, these oocytes lack development up to the preovulatory stage and
      are matured in vitro. Therefore, much effort has been devoted to the
      establishment of non-invasive and non-perturbing means for selecting the most
      competent oocytes, for example the extensiveness and compactness of the cumulus
      corona investment and the granulation of the ooplasm. In vitro culture (IVC)
      conditions have been enhanced in the last few years, mainly by adjustment of
      media formulations, whereas the in vitro maturation (IVM) protocols stay
      invariable. Consequently, maintaining or mimicking the in vivo situation in vitro
      will aid to improve the quality and developmental competence of the resulting
      matured oocyte. The scope of this review is to give an overview of the current
      situation of in vitro maturation of mammalian oocytes with emphasis on the bovine
      species. Special attention has been paid to the in vivo situation in the follicle
      and how a better understanding of these intrafollicular factors will aid to
      improve the in vitro maturation conditions.

PMID- 23962214
TI  - Hypothalamic integration of nutrient status and reproduction in the sheep.
AB  - Nutrient availability is a determinant of reproductive success. It is well known
      that inadequate nutrition results in reproductive failure due to a number of
      factors including delay of puberty or anoestrous in post-pubertal animals. The
      lack of nutrients is detected primarily by changes in circulating nutrient
      molecules and hormones and communicated directly or indirectly to the
      hypothalamus and brain stem for integration. The general effect is that low
      nutrition leads to increased appetite stimulation and reduced reproductive
      performance. When nutrition is adequate, the reverse is true. Both aspects will
      be the focus of this review. One result of the lack of nutrients is a reduction
      in luteinizing hormone (LH) concentrations and pulse frequency. Nutrient signals,
      such as glucose availability, hormonal signals, such as insulin and leptin, and
      neuroendocrine signals, such as neuropeptide Y and corticotropin-releasing
      hormone, have been clearly demonstrated to interact to produce changes in LH and
      reproductive success. Other signals, such as fatty acids, ghrelin, agouti-related
      peptide, melanin-concentrating hormone, orexin, melanocyte-stimulating hormone,
      kisspeptin, neurokinin, dynorphin and gonadotropin inhibitory hormone may also
      play a role in integrating nutrition and reproduction. This review will focus on
      the major features of the reciprocal control of appetite and reproduction in
      sheep. 

PMID- 23962215
TI  - Drivers of post-partum uterine disease in dairy cattle.
AB  - Post-partum uterine disease has a detrimental effect on dairy cow fertility;
      affected cows require more serves per conception, have reduced conception rates
      and are more likely to be culled for infertility. Furthermore, the detrimental
      effects on fertility remain even after clinical resolution of disease. There are
      many factors that influence a cow's resistance to or development of post-partum
      disease, and the key drivers determining disease outcome are uterine microbial
      load, regulation of inflammation and immune responses peripherally and at a local
      level, production pressure, and metabolic (energy) status. These factors are
      intricately interlinked, which makes assessment of their individual effects
      difficult. It is clear, however, that the period surrounding calving is a key
      transition phase and events during this time point will influence uterine disease
      outcome and subsequent fertility. Good peripartum management and accurate
      diagnosis are critical to facilitate the use of the most effective treatment and
      limit the negative impact of post-partum uterine disease on fertility. If we can
      improve our understanding of the underlying causes of disease, then we can
      identify 'at risk' animals and implement management and breeding strategies to
      prevent uterine disease or reduce its severity. Thus, this article aims to
      summarize the key factors that drive uterine disease in the post-partum dairy
      cow. 

PMID- 23962218
TI  - An optimized device for staining electron microscopy grids.
AB  - Proper staining of grids is critical for transmission electron microscopy (TEM).
      Staining must be done as quickly as possible using minimal reagents and with
      consideration for the environment. We developed a new device for efficient
      staining of multiple TEM grids. We studied reagent evaporation, rinsing volume,
      flow rate and re-use of uranyl acetate, and provide here a procedure for
      efficient staining using the new device. Our device permits TEM grids to be
      stained with less reagent than alternative staining apparatuses; staining
      requires a total volume of 260 MUl for five grids. Reagent evaporation is less
      than 6% even if used at 37 degrees  C. Moreover, our staining apparatus reduces
      chemical waste and shortens experiment time by staining several grids
      simultaneously. Our staining device is a compromise between time-consuming single
      grid processing and expensive commercial devices that consume large amounts of
      reagents.

PMID- 23962219
TI  - Targeted sequence capture and resequencing implies a predominant role of
      regulatory regions in the divergence of a sympatric lake whitefish species pair
      (Coregonus clupeaformis).
AB  - Latest technological developments in evolutionary biology bring new challenges in
      documenting the intricate genetic architecture of species in the process of
      divergence. Sympatric populations of lake whitefish represent one of the key
      systems to investigate this issue. Despite the value of random genotype-by
      sequencing methods and decreasing cost of sequencing technologies, it remains
      challenging to investigate variation in coding regions, especially in the case of
      recently duplicated genomes as in salmonids, as this greatly complicates whole
      genome resequencing. We thus designed a sequence capture array targeting 2773
      annotated genes to document the nature and the extent of genomic divergence
      between sympatric dwarf and normal whitefish. Among the 2728 genes successfully
      captured, a total of 2182 coding and 10,415 noncoding putative single-nucleotide
      polymorphisms (SNPs) were identified after applying a first set of basic filters.
      A genome scan with a quality-refined selection of 2203 SNPs identified 267
      outlier SNPs in 210 candidate genes located in genomic regions potentially
      involved in whitefish divergence and reproductive isolation. We found highly
      heterogeneous FST estimates among SNP loci. There was an overall low level of
      coding polymorphism, with a predominance of noncoding mutations among outliers.
      The heterogeneous patterns of divergence among loci confirm the porous nature of
      genomes during speciation with gene flow. Considering that few protein-coding
      mutations were identified as highly divergent, our results, along with previous
      transcriptomic studies, imply that changes in regulatory regions most likely had
      a greater role in the process of whitefish population divergence than protein
      coding mutations. This study is the first to demonstrate the efficiency of large
      scale targeted resequencing for a nonmodel species with such a large and
      unsequenced genome.

PMID- 23962220
TI  - Evaluation of multisystemic therapy pilot services in the Systemic Therapy for At
      Risk Teens (START) trial: study protocol for a randomised controlled trial.
AB  - BACKGROUND: There is an urgent need for clinically effective and cost-effective
      methods to manage antisocial and criminal behaviour in adolescents. Youth conduct
      disorder is increasingly prevalent in the UK and is associated with a range of
      negative outcomes. Quantitative systematic reviews carried out for the National
      Institute for Health and Clinical Excellence have identified multisystemic
      therapy, an intensive, multimodal, home-based, family intervention for youth with
      serious antisocial behaviour, as one of the most promising interventions for
      reducing antisocial or offending behaviour and improving individual and family
      functioning. Previous international trials of multisystemic therapy have yielded
      mixed outcomes, and it is questionable to what extent positive US findings can be
      generalised to a wider UK mental health and juvenile justice context. This paper
      describes the protocol for the Systemic Therapy for At Risk Teens (START) trial,
      a multicentre UK-wide randomised controlled trial of multisystemic therapy in
      antisocial adolescents at high risk of out-of-home placement. METHODS/DESIGN: The
      trial is being conducted at 10 sites across the UK. Seven hundred participants
      and their families will be recruited and randomised on a 1:1 basis to
      multisystemic therapy or management as usual. Treatments are offered over a
      period of 3 to 5 months, with follow-up to 18 months post-randomisation. The
      primary outcome is out-of-home placement at 18 months. Secondary outcomes include
      offending rates, total service and criminal justice sector costs, and participant
      well-being and educational outcomes. Data will be gathered from police computer
      records, the National Pupil Database, and interview and self-report measures
      administered to adolescents, parents and teachers. Outcomes will be analysed on
      an intention-to-treat basis, using a logistic regression with random effects for
      the primary outcome and Cox regressions and linear mixed-effects models for
      secondary outcomes depending on whether the outcome is time-to-event or
      continuous. DISCUSSION: The START trial is a pragmatic national trial of
      sufficient size to evaluate multisystemic therapy, to inform policymakers,
      service commissioners, professionals, service users and their families about its
      potential in the UK. It will also provide data on the clinical and cost
      effectiveness of usual services provided to youth with serious antisocial
      behaviour problems. TRIAL REGISTRATION: ISRCTN77132214.

PMID- 23962222
TI  - Core-shell-corona polymeric micelles as a versatile template for synthesis of
      inorganic hollow nanospheres.
AB  - Hollow, inorganic nanoscale capsules have many applications, from the delivery of
      encapsulated products for cosmetic and medicinal purposes to use as lightweight
      composite materials. Early methods for producing inorganic hollow nanospheres
      using hard templates suffered from low product yield and shell weakness upon
      template removal. In the past decade, researchers have turned to amphiphilic
      copolymers to synthesize hollow nanostructures and ordered mesoporous materials.
      Amphiphilic molecules self-assemble into well-defined nanostructures including
      spherical micelles. Micelles formed from simple, two-component AB diblock and ABA
      triblock copolymers, however, have been difficult to work with to construct
      inorganic hollow nanoparticles, because the corona of the micelle, which serves
      as the template for the shell, becomes unstable as it absorbs inorganic shell
      precursors, causing aggregates to form. Newly developed, three-component ABC
      triblock copolymers may solve this problem. They provide nanoassemblies with more
      diverse morphological and functional features than AB diblock and ABA triblock
      copolymers. Micelles formed from ABC triblock copolymers in selective solvents
      that dissolve only one or two of the blocks provide templates for these improved
      nanoassemblies. By manipulating individual polymer blocks, one can "encode"
      additional features at the molecular level. For instance, modifying the
      functional groups or substitution patterns of the blocks allows better
      morphological and size control. Insights into polymer self-assembly gained over
      years of work in our group have set the stage to systematically engineer
      inorganic spherical hollow nanoparticles using ABC triblock copolymers. In this
      Account, we report our recent progress in producing diverse, inorganic hollow
      spherical nanospheres from asymmetric triblock copolymeric micelles with core
      shell-corona architecture as templates. We discuss three classes of polymeric
      micelles-with neutral, cationic, and anionic shell structures-that allow
      fabrication of a variety of hollow nanoparticles. Importantly, we synthesized all
      of these particles in water, avoiding use of hazardous organic solvents. We have
      designed the precursor of the inorganic material to be selectively sorbed into
      the shell domain, leaving the corona free from the inorganic precursors that
      would destabilize the micelle. The core, meanwhile, is the template for the
      formation of the hollow void. By rationally tailoring experimental parameters, we
      readily and selectively obtained a variety of hollow nanoparticles including
      silica, hybrid silicas, metal-oxides, metal-carbonates, metal-sulfates, metal
      borates, and metal-phosphates. Finally, we highlight the state-of-the-art
      techniques we used to characterize these nanoparticles, and describe experiments
      that demonstrate the potential of these hollow particles in drug delivery, and as
      anode and cathode materials for lithium-ion batteries. 

PMID- 23962223
TI  - A practical and convenient protocol for the synthesis of (E)-alpha,beta
      unsaturated acids.
AB  - alpha,beta-Unsaturated acids are very useful and versatile reagents in organic
      synthesis. A novel, practical, and convenient catalytic protocol comprising
      FeCl3.6H2O (0.5 mol %) and H2O (1 equiv) in CH3NO2 is described for the rapid
      synthesis of alpha,beta-unsaturated acids with high E-stereoselectivity under
      both microwave and conventional heating conditions with high TON and TOF values.
      This powerful approach efficiently demonstrated the utility of biomass derived
      aldehydes to build chemical agents used as fuel additives. The method proved to
      be scalable to gram scale synthesis. 

PMID- 23962221
TI  - The current state of active third stage management to prevent postpartum
      hemorrhage: a cross-sectional study.
AB  - OBJECTIVE: To investigate the implementation of the International Confederation
      of Midwives/International Federation of Gynecology and Obstetrics (ICM/FIGO)
      guideline on active third stage management in vaginal deliveries in daily
      clinical practice. DESIGN: Observational, cross-sectional study. SETTING: One
      tertiary and one teaching hospital in the Netherlands. POPULATION: Women
      undergoing vaginal deliveries. METHODS: A case record form was completed after
      every vaginal delivery. Primary outcome was adequate guideline adherence, defined
      as initial administration of 10 IU oxytocin, performance of controlled cord
      traction and uterine massage. Adequate guideline adherence was a priori estimated
      to be 10%. With a sample size of 600, i.e. 300 women per hospital, the standard
      error of the resulting percentage would be less than 2% for each hospital.
      RESULTS: Six hundred and twenty six women were included. Guideline adherence was
      adequately performed in 48% of vaginal deliveries. Oxytocin was administered
      after birth in 98% of deliveries and in 80% the correct dose was used. Controlled
      cord traction was performed in 63% and uterine massage in 93%; however, the
      latter was performed as advised (at least eight times) in only 8%. The amount of
      blood loss was not associated with the use of either 5 or 10 IU oxytocin (p =
      0.818). Controlled cord traction and uterine massage were more frequently
      performed when blood loss exceeded 500 mL (p < 0.001). CONCLUSIONS: Active third
      stage management according to the ICM/FIGO guideline is adequately performed in
      only 48% of all vaginal deliveries. Results of this study call for training
      programs to increase adherence to the ICM/FIGO guideline.

PMID- 23962224
TI  - National Chemical Landmark award to USDA-ARS center.

PMID- 23962226
TI  - A scenario and forecast model for Gulf of Mexico hypoxic area and volume.
AB  - For almost three decades, the relative size of the hypoxic region on the
      Louisiana-Texas continental shelf has drawn scientific and policy attention.
      During that time, both simple and complex models have been used to explore
      hypoxia dynamics and to provide management guidance relating the size of the
      hypoxic zone to key drivers. Throughout much of that development, analyses had to
      accommodate an apparent change in hypoxic sensitivity to loads and often cull
      observations due to anomalous meteorological conditions. Here, we describe an
      adaptation of our earlier, simple biophysical model, calibrated to revised
      hypoxic area estimates and new hypoxic volume estimates through Bayesian
      estimation. This application eliminates the need to cull observations and
      provides revised hypoxic extent estimates with uncertainties corresponding to
      different nutrient loading reduction scenarios. We compare guidance from this
      model application, suggesting an approximately 62% nutrient loading reduction is
      required to reduce Gulf hypoxia to the Action Plan goal of 5000 km(2), to that of
      previous applications. In addition, we describe for the first time, the
      corresponding response of hypoxic volume. We also analyze model results to test
      for increasing system sensitivity to hypoxia formation, but find no strong
      evidence of such change. 

PMID- 23962227
TI  - Effect of thrombocytopenia on mode of analgesia/anesthesia and maternal and
      neonatal outcomes.
AB  - OBJECTIVES: The purpose was to correlate the use of regional analgesia/anasthesia
      among women with different degrees of thrombocytopenia relative to women with
      normal platelet counts, and note maternal and neonatal outcome, and mode of
      delivery. METHODS: A case-control paradigm was developed based on women who
      delivered during 2007-2011 with platelet counts <=80 000/mm(3). For each woman in
      this "severe" thrombocytopenic group, an age- and parity-matched control was
      found who delivered a singleton within the same year but whose platelets were
      either 81 000-150 000/mm(3) ("moderate" thrombocytopenia) or >=151 000/mm(3)
      (normal platelet counts). RESULTS: 168 women were identified for each group; mean
      maternal age (28.4 years), mean gravidity (4.3), mean parity (3.7), mean
      gestational age (39.2 weeks) and mean birth weight (3283 g) were comparable.
      However, only in the severe thrombocytopenic women were there very early preterm
      deliveries, lowest birth weight, lowest Apgar scores, the greatest number with
      serious post-partum hemorrhage (>500 ml); use of regional analgesia/anesthesia
      was lowest, and percent cesarean sections highest. CONCLUSIONS: This study
      highlights potential for adverse maternal outcome of post-partum hemorrhage and
      adverse neonatal outcomes of prematurity, low birth weight, and low Apgar scores
      (but not neonatal death), and limited regional analgesia/anesthesia in women who
      present at delivery with severe (<=80 000/mm(3)) thrombocytopenia.

PMID- 23962225
TI  - Association between presence of the metabolic syndrome and its components with
      carotid intima-media thickness and carotid and femoral plaque area: a population
      study.
AB  - BACKGROUND: We aimed to explore the association between presence and number of
      components of the Metabolic Syndrome (MetS) and subclinical atherosclerosis
      outcomes (common carotid intima media thickness, plaque presence and sum of
      plaque area) in both the carotid and femoral bifurcations. METHODS: Cross
      sectional analysis of 771 volunteers from the ongoing epidemiological Cyprus
      Study (46% male; mean age = 60.1 +/- 9.8). (a) Carotid intima-media thickness
      (IMTcc), (b) sum of plaque area in the carotid bifurcations (sum of the largest
      plaques in each carotid bifurcation-SPAcar), (c) sum of plaque area in the
      femoral bifurcations (sum of the largest plaques in each femoral bifurcation
      SPAfem) and (d) sum of plaque area in both carotid and femoral bifurcations (sum
      of the areas of the largest plaques present in each of the four bifurcations-SPA)
      were measured at baseline using ultrasound. Presence and number of components of
      the MetS was ascertained using the National Cholesterol Education Program ATPIII
      definition and their association tested using multivariable regression models.
      RESULTS: MetS was present in 259 (33.6%) individuals and was associated with a
      0.02 mm increase in IMTcc (95% CI: 0.00 to 0.04, p = 0.047) after adjustment for
      age, sex, family history of CVD, alcohol consumption (BU/week) and smoking (pack
      years). Each additional component of the MetS was associated with a 16% higher
      SPA (95% CI: 6.8% to 25.2%, pfor trend = 0.001), a 10% higher SPAcar (95% CI: 5%
      to 24%, pfor trend = 0.003) and a 14% higher SPAfem in the adjusted model.
      CONCLUSIONS: We confirm an association between the MetS and IMTcc as well as
      report for the first time an association between the MetS and its components and
      femoral plaque area, in a general population over 40 years of age. Having any
      risk factors for the MetS increases the risk for subclinical atherosclerosis,
      with the risk increasing with each additional component. Using the dichotomous
      definition of the MetS may be overlooking the risk for subclinical
      atherosclerosis -and by inference future cardiovascular events- associated with
      having less than 3 risk factors.

PMID- 23962228
TI  - Hierarchial coassembly of a cyanine dye in poly(vinyl alcohol) fibrous films by
      electrospinning.
AB  - We report molecular aggregate formation of TTBC (1,1',3,3'-tetraethyl-5,5',6,6'
      tetrachlorobenzimidazolocarbocyanine) in submicrometer-sized PVA (poly(vinyl
      alcohol)) fibers by electrospinning. The formation of the molecular aggregate is
      examined by solution and instrumental parameters of electrospinning. The
      precursor solution of PVA/TTBC, in the range of 0.016-0.065 wt % is subjected to
      electrospinning under an electrical field ranging from 0.95 to 1.81 kV cm(-1).
      Both randomly deposited and uniaxially aligned fibers are achieved by using two
      parallel-positioned metal strips as counter electrode. Photoluminescence and
      polarized Fourier transform infrared spectroscopies are employed to determine
      spectral properties of the fibers. H-aggregates are formed within the electrospun
      fibers, regardless of their alignment, and H- and J-type aggregates coexist in
      the alternative spin-coated and the cast films. A strongly polarized
      photoluminescence emission is observed in the direction of uniaxially aligned
      fibers as a result of the orientation of the H-aggregates along the fiber axis.
      We demonstrate that electrospinning is a process capable of forming and orienting
      TTBC aggregates during the structural development of the polymer/dye nanofibers.
      These fibrous films may potentially find applications in optics and electronics. 

PMID- 23962229
TI  - Impact of an intercalated BSc on medical student performance and careers: a BEME
      systematic review: BEME Guide No. 28.
AB  - INTRODUCTION: Intercalated BScs (iBScs) are an optional part of undergraduate
      (UG) medicine courses in UK, Eire, Australia, New Zealand, the West Indies, Hong
      Kong, South Africa and Canada, consisting of advanced study into a particular
      field of medicine, often combined with research. They potentially improve
      students' skills and allow exploration of specific areas of interest. They are,
      however, expensive for institutions and students and delay workforce entry. There
      is conflicting evidence about their impact. METHODS: A mixed-method systematic
      review (meta-analysis and critical interpretive synthesis) of the biomedical and
      educational literature, focusing on the impact of iBScs on UG performance,
      skills, and career choice, and to explore students' and other stakeholders'
      opinions about iBScs. RESULTS: In the meta-analytic part of this review, we
      identified five studies which met our predetermined quality criteria. For UG
      performance, two studies using different methodologies report an improvement in
      UG performance; one study reported an Odds Ratio [OR] of 3.58 [95% CI 1.47-8.83]
      and the second reported a significant improvement in finals scores (1.27 points
      advantage 95% CI 0.52-2.02). One study reported a mixed result, while two studies
      showed no improvement. Regarding skills and attitudes, one paper suggested iBScs
      lead to the development of deeper learning styles. With regard to subsequent
      careers, two studies suggested that for those students undertaking an iBSc there
      is an increased chance following an academic career [ORs of 3.6 (2.3-5.8) to 5.94
      (3.6-11.5)]. Seven of eight studies (with broader selection criteria) reported
      that iBSc students were less likely to pursue GP careers (ORs no effect to 0.17
      [0.07-0.36]). Meta-analysis of the data was not possible. In the critical
      interpretative synthesis analysis, we identified 46 articles, from which three
      themes emerged; firstly, the decision to undertake an iBSc, with students
      receiving conflicting advice; secondly, the educational experience, with
      intellectual growth balanced against financial costs; finally, the ramifications
      of the iBSc, including some suggestion of improved employment prospects and the
      potential to nurture qualities that make "better" doctors. CONCLUSION:
      Intercalated BScs may improve UG performance and increase the likelihood of
      pursuing academic careers, and are associated with a reduced likelihood of
      following a GP career. They help students to develop reflexivity and key skills,
      such as a better understanding of critical appraisal and research. The decision
      to undertake an iBSc is contentious; students feel ill-informed about the
      benefits. These findings could have implications for a variety of international
      enrichment programmes.

PMID- 23962231
TI  - Targeting patients for multimorbid care management interventions: the case for
      equity in high-risk patient identification.
AB  - Targeting patients for multimorbid care management interventions requires
      accurate and comprehensive assessment of patients' need in order to direct
      resources to those who need and can benefit from them the most. Multimorbid
      patient selection is complicated due to the lack of clear criteria--unlike
      disease management programs for which patients with a specific condition are
      identified. This ambiguity can potentially result in inequitable selection, as
      biases in selection may differentially affect patients from disadvantaged
      population groups. Patient selection could in principal be performed in three
      ways: physician referral, patient screening surveys, or by statistical prediction
      algorithms. This paper discusses equity issues related to each method. We
      conclude that each method may result in inequitable selection and bias, such as
      physicians' attentiveness or familiarity, or prediction models' reliance on prior
      resource use, potentially affected by socio-cultural and economic barriers. These
      biases should be acknowledged and dealt with. We recommend combining patient
      selection approaches to achieve high care sensitivity, efficiency and equity.

PMID- 23962230
TI  - Factors influencing the surgery intentions and choices of women with early breast
      cancer: the predictive utility of an extended theory of planned behaviour.
AB  - BACKGROUND: Women diagnosed with early breast cancer (stage I or II) can be
      offered the choice between mastectomy or breast conservation surgery with
      radiotherapy due to equivalence in survival rates. A wide variation in the
      surgical management of breast cancer and a lack of theoretically guided research
      on this issue highlight the need for further research into the factors
      influencing women's choices. An extended Theory of Planned Behaviour (TPB) could
      provide a basis to understand and predict women's surgery choices. The aims of
      this study were to understand and predict the surgery intentions and choices of
      women newly diagnosed with early breast cancer, examining the predictive utility
      of an extended TPB. METHODS: Sixty-two women recruited from three UK breast
      clinics participated in the study; 48 women, newly diagnosed with early breast
      cancer, completed online questionnaires both before their surgery and after
      accessing an online decision support intervention (BresDex). Questionnaires
      assessed views about breast cancer and the available treatment options using
      items designed to measure constructs of an extended TPB (i.e., attitudes,
      subjective norms, perceived behavioural control, and anticipated regret), and
      women's intentions to choose mastectomy or BCS. Objective data were collected on
      women's choice of surgery via the clinical breast teams. Multiple and logistic
      regression analyses examined predictors of surgery intentions and subsequent
      choice of surgery. RESULTS: The extended TPB accounted for 69.9% of the variance
      in intentions (p <.001); attitudes and subjective norms were significant
      predictors. Including additional variables revealed anticipated regret to be a
      more important predictor than subjective norms. Surgery intentions significantly
      predicted surgery choices (p <.01). CONCLUSIONS: These findings demonstrate the
      utility of an extended TPB in predicting and understanding women's surgery
      intentions and choices for early breast cancer. Understanding these factors
      should help to identify key components of interventions to support women while
      considering their surgery options.

PMID- 23962232
TI  - Evaluation of a short-term group psychotherapy used as part of the rehabilitation
      process in nursing home patients.
AB  - PURPOSE: The aim of this study was to assess the impact of a 4-week group
      psychotherapy on the efficacy of physiotherapy in patients rehabilitated in a
      nursing home (NH). MATERIALS AND METHODS: The study was performed on 28 women,
      aged 77.1 (+/-5.6) years. Thirty-six percent were rehabilitated due to
      orthopaedic injuries, 36% had undergone a stroke, 28% suffered from chronic
      diseases of old age. Subjects were divided into two groups: experimental (n = 13)
      and control (n = 15). In the experimental group, a short-term, goal-focused group
      psychotherapy was used. To assess cognitive impairment, mood and functional
      status the Mini Mental State Examination (MMSE), the Geriatric Depression Scale
      (GDS-15) and the Barthel Index (BI) were used. RESULTS: In the experimental group
      a four times greater improvement in mood was observed and two times greater
      physiotherapy efficacy (PE) in the first month of stay in an NH as compared to
      the control group. The effects of psychotherapy were independent of the type of
      disease, the patients' age, number of comorbidities and cognitive status (ranging
      from 15 to 30 points on the MMSE). CONCLUSIONS: Short-term group psychotherapy
      can be an effective method of supporting the process of rehabilitating older,
      disabled people rehabilitated in an NH. IMPLICATIONS FOR REHABILITATION:
      Psychotherapy can improve the efficacy of treatment and rehabilitation in
      different somatic illnesses despite the advanced age of respondents, high
      disability rate, and the presence of cognitive impairments. Even short-term (4
      weeks) group psychotherapy can provide effective support for the rehabilitation
      in the elderly.

PMID- 23962233
TI  - Cyclodextrin-based microcapsules as bioreactors for ATP biosynthesis.
AB  - A biomimetic energy converter was fabricated via the assembly of CF0F1-ATPase on
      lipid-coated hollow nanocapsules composed of alpha-cyclodextrins/chitosan-graft
      poly(ethylene glycol) methacrylate. Upon entrapped GOD into these capsules, the
      addition of glucose could trigger proton-motive force and then drive the rotation
      of ATPase to synthesize ATP. 

PMID- 23962234
TI  - The medicinal potential of natural products for the development of anti-
      influenza agents.
AB  - Influenza neuraminidase (NA) is an important target for designing anti-influenza
      drugs. By now, three inhibitors, zanamivir, oseltamivir and peramivir have been
      approved. However, in recent years, the potential threat of influenza pandemics
      and constant emergence of new drug-resistant influenza virus strains have weaken
      the defensive role of the current anti-influenza drugs. From another point of
      view, in this review we focused on some novel NA inhibitors which were mainly
      derived from natural products that had a variety of structural scaffolds, such as
      flavonoids, xanthones and diarylheptanoids. Besides interfering the function of
      NA, some of these compounds also can potently inhibit the replication of
      influenza virus. It is hoped that these compounds could be the source of leads
      and provide a guide for discovering new potent anti-influenza virus agents. 

PMID- 23962235
TI  - GarA is an essential regulator of metabolism in Mycobacterium tuberculosis.
AB  - Alpha-ketoglutarate is a key metabolic intermediate at the crossroads of carbon
      and nitrogen metabolism, whose fate is tightly regulated. In mycobacteria the
      protein GarA regulates the tricarboxylic acid cycle and glutamate synthesis by
      direct binding and regulation of three enzymes that use alpha-ketoglutarate.
      GarA, in turn, is thought to be regulated via phosphorylation by protein kinase G
      and other kinases. We have investigated the requirement for GarA for metabolic
      regulation during growth in vitro and in macrophages. GarA was found to be
      essential to Mycobacterium tuberculosis, but dispensable in non-pathogenic
      Mycobacterium smegmatis. Disruption of garA caused a distinctive, nutrient
      dependent phenotype, fitting with its proposed role in regulating glutamate
      metabolism. The data underline the importance of the TCA cycle and the balance
      with glutamate synthesis in M. tuberculosis and reveal vulnerability to
      disruption of these pathways. 

PMID- 23962236
TI  - At the bench: the key role of PK-PD modelling in enabling the early discovery of
      biologic therapies.
AB  - Pharmacokinetic-pharmacodynamic (PK-PD) modelling is already used extensively in
      pre-clinical and clinical drug development to characterize drug candidates
      quantitatively, aid go/no-go decisions and to inform future trial design and
      optimal dosing regimens. Less well known, although arguably as powerful, is its
      application at the earliest stages of drug development, at target selection and
      lead selection, where these same techniques can be used to predict and so bring
      forward drug candidates with the necessary characteristics or, for unachievable
      requirements, allow the abandonment of the programme for the minimum spend of
      time and cost. We consider three examples that illustrate the power of the
      application of modelling at this early stage. We start with the simple case of
      determining the optimal characteristics for a monoclonal antibody against a
      soluble ligand with its application to the investment decision for the
      development of best-in-class compounds. This is extended to the more complex
      situation of the target protein having an endogenous, inhibitory binding protein.
      We then illustrate how using physiologically-based pharmacokinetic modelling
      enables the appropriate engineering and testing of biological therapeutics for
      optimal PK-PD characteristics. These examples illustrate how a minimal investment
      in modelling achieves orders of magnitude better returns in choosing the correct
      targets, mechanism of action and candidate characteristics to progress to
      clinical trials, streamlining drug development and delivering better medicines to
      patients. 

PMID- 23962237
TI  - Loss of Oca2 disrupts the unfolded protein response and increases resistance to
      endoplasmic reticulum stress in melanocytes.
AB  - Accumulation of proteins in the endoplasmic reticulum (ER) typically induces
      stress and initiates the unfolded protein response (UPR) to facilitate recovery.
      If homeostasis is not restored, apoptosis is induced. However, adaptation to
      chronic UPR activation can increase resistance to subsequent acute ER stress. We
      therefore investigated adaptive mechanisms in Oculocutaneous albinism type 2
      (Oca2)-null melanocytes where UPR signaling is arrested despite continued
      tyrosinase accumulation leading to resistance to the chemical ER stressor
      thapsigargin. Although thapsigargin triggers UPR activation, instead of Perk
      mediated phosphorylation of eIF2alpha, in Oca2-null melanocytes, eIF2alpha was
      rapidly dephosphorylated upon treatment. Dephosphorylation was mediated by the
      Gadd34-PP1alpha phosphatase complex. Gadd34-complex inhibition blocked eIF2alpha
      dephosphorylation and significantly increased Oca2-null melanocyte sensitivity to
      thapsigargin. Thus, Oca2-null melanocytes adapt to acute ER stress by disruption
      of pro-apoptotic Perk signaling, which promotes cell survival. This is the first
      study to demonstrate rapid eIF2alpha dephosphorylation as an adaptive mechanism
      to ER stress. 

PMID- 23962239
TI  - A versatile near-infrared asymmetric tricarbocyanine for zinc ion sensing in
      water.
AB  - We have synthesized a near-infrared emissive asymmetric tricarbocyanine
      conveniently functionalized to improve bioconjugation. The leading structure
      contains a versatile derivatization point at the meso position for facile radical
      nucleophilic aromatic substitution. We have evaluated a DPEN (N,N-di(2
      picolyl)ethylendiamine) derivative of this dye as a highly selective sensor for
      zinc (II) in aqueous medium, which performs in an appropriate sensitivity range
      for biological studies. The probe was successfully conjugated to a protein-ligand
      model with high affinity and specificity (biotin-streptavidin technology)
      rendering an excellent performance of sensing. In a general strategy to obtain
      sensitive probes combining fluorescent nanoparticles and molecular fluorophores,
      a preliminary design of a supramolecular assembly derived from the conjugation of
      the molecular sensor to quantum dots (QDs) was also investigated. The advantages
      and problems of FRET-based sensors are also discussed. 

PMID- 23962240
TI  - Three new diterpenoids from the resin of Liquidambar formosana.
AB  - Three new diterpenoids, liquidambolide A (1) and liquiditerpenoic acids A (2) and
      B (3), together with 10 known diterpenes were isolated from the resin of
      Liquidambar formosana Hance, whose structures were elucidated by detailed
      analysis on the NMR and HR-ESI-MS spectra. 

PMID- 23962238
TI  - Rift Valley fever virus structural and nonstructural proteins: recombinant
      protein expression and immunoreactivity against antisera from sheep.
AB  - The Rift Valley fever virus (RVFV) encodes the structural proteins nucleoprotein
      (N), aminoterminal glycoprotein (Gn), carboxyterminal glycoprotein (Gc), and L
      protein, 78-kD, and the nonstructural proteins NSm and NSs. Using the baculovirus
      system, we expressed the full-length coding sequence of N, NSs, NSm, Gc, and the
      ectodomain of the coding sequence of the Gn glycoprotein derived from the
      virulent strain of RVFV ZH548. Western blot analysis using anti-His antibodies
      and monoclonal antibodies against Gn and N confirmed expression of the
      recombinant proteins, and in vitro biochemical analysis showed that the two
      glycoproteins, Gn and Gc, were expressed in glycosylated form. Immunoreactivity
      profiles of the recombinant proteins in western blot and in indirect enzyme
      linked immunosorbent assay against a panel of antisera obtained from vaccinated
      or wild type (RVFV)-challenged sheep confirmed the results obtained with anti-His
      antibodies and demonstrated the suitability of the baculo-expressed antigens for
      diagnostic assays. In addition, these recombinant proteins could be valuable for
      the development of diagnostic methods that differentiate infected from vaccinated
      animals (DIVA).

PMID- 23962241
TI  - Proton and carbon ion radiotherapy for primary brain tumors and tumors of the
      skull base.
AB  - To analyze clinical concepts, toxicity and treatment outcome in patients with
      brain and skull base tumors treated with photons and particle therapy. MATERIAL
      AND METHODS: In total 260 patients with brain tumors and tumors of the skull base
      were treated at the Heidelberg Ion Therapy Center (HIT). Patients enrolled in and
      randomized within prospective clinical trials as well as bony or soft tissue
      tumors are not included in this analysis. Treatment was delivered as protons,
      carbon ions, or combinations of photons and a carbon ion boost. All patients are
      included in a tight follow-up program. The median follow-up time is 12 months
      (range 2-39 months). RESULTS: Main histologies included meningioma (n = 107) for
      skull base lesions, pituitary adenomas (n = 14), low-grade gliomas (n = 51) as
      well as high-grade gliomas (n = 55) for brain tumors. In all patients treatment
      could be completed without any unexpected severe toxicities. No side effects >
      CTC Grade III were observed. To date, no severe late toxicities were observed,
      however, for endpoints such as secondary malignancies or neurocognitive side
      effects follow-up time still remains too short. Local recurrences were mainly
      seen in the group of high-grade gliomas or atypical meningiomas; for benign skull
      base meningiomas, to date, no recurrences were observed during follow-up.
      CONCLUSION: The specific benefit of particle therapy will potentially reduce the
      risk of secondary malignancies as well as improve neurocognitive outcome and
      quality of life (QOL); thus, longer follow-up will be necessary to confirm these
      endpoints. Indication-specific trials on meningiomas and gliomas are underway to
      elucidate the role of protons and carbon ions in these indications.

PMID- 23962242
TI  - MRI-guided adaptive radiotherapy in locally advanced cervical cancer from a
      Nordic perspective.
AB  - BACKGROUND: The first Nordic protocol for three-dimensional (3D) planned
      radiotherapy in locally advanced cervical cancer was the prospective NOCECA study
      (1994-2000). NOCECA consisted of computed tomography (CT)-based 3D conformal
      external beam radiotherapy (EBRT) with a simultaneous integrated boost (SIB) to
      the primary tumour combined with brachytherapy (BT) based on x-ray imaging. In
      NOCECA the planning aim was to achieve 80 Gy at point A from EBRT and BT
      combined. However, the balance of dose between EBRT and BT was determined by
      tumour size at diagnosis with more EBRT dose given to point A and less by BT in
      more advanced stages. In 2005 image-guided adaptive brachytherapy (IGABT) based
      on magnetic resonance imaging (MRI) and optimisation of the BT dose distribution
      to the remaining tumour and cervix at time of BT (HR CTV) was introduced in
      Aarhus. EBRT remained like in NOCECA until 2008 when the SIB to the primary
      tumour was abandoned and IMRT was introduced as routine technique. In this study,
      we report outcome of our first five-year experience with IGABT using our NOCECA
      cohort as reference. MATERIAL AND METHODS: The NOCECA cohort comprising 99
      patients was compared with 140 consecutive patients treated by IGABT. Patients
      with para-aortic nodes were excluded in NOCECA but were present in 9% of the
      patients treated with IGABT. No patient in NOCECA received chemotherapy whereas
      concomitant cisplatin was given to 79% of the IGABT patients. RESULTS: With IGABT
      actuarial local control was 91% at three years. When comparing NOCECA with IGABT
      overall survival was significantly improved from 63% to 79% (p = 0.005). In
      parallel, both moderate and severe late morbidity were reduced by about 50% (p =
      0.02). CONCLUSION: Introduction of IGABT reduced morbidity and generated a very
      high rate of local control, which likely has improved survival by at least as
      much as concomitant chemotherapy.

PMID- 23962243
TI  - PET imaging of tumor hypoxia using 18F-labeled pimonidazole.
AB  - BACKGROUND: Tumor hypoxia contributes to loco-regional failure, and for optimal
      treatment planning, knowledge about tumor hypoxia in individual patients is
      required. Nitroimidazole-based tracers, which are retained in hypoxic cells,
      allow PET-based assessment of tumor hypoxia, but current tracers are
      characterized by slow tracer retention and clearance, resulting in low inter
      tissue contrast. Pimonidazole is an immune detectable hypoxia marker widely used
      for detection of hypoxia in tumor samples. Pimonidazole has excellent chemical
      properties for hypoxia imaging, but labeling for non- invasive assay has not been
      attempted. Here we labeled pimonidazole with (18)F ([(18)F]FPIMO). MATERIAL AND
      METHODS: [(18)F]FPIMO was produced by fluorination of 1-[2-O-tosyl-3-(2
      nitroimidazole-1-yl)-propyl]-piperidine, which resulted in two isomeric
      interchangeable forms (named "5" and "6") with a radiochemical purity of 91-100%.
      [(18)F]FPIMO was tested by incubation of two different tumor cell lines at high
      and low oxygen levels. [(18)F]FPIMO was also administered to tumor-bearing mice
      and tracer retention in tumors, non-hypoxic reference tissues and tissues
      involved in drug metabolism/clearance was evaluated by various techniques.
      RESULTS AND CONCLUSIONS: Retention of [(18)F]FPIMO was strongly hypoxia-driven in
      vitro, but isomeric form "5" was particularly promising and reached impressive
      anoxic-to-oxic retention ratios of 36 and 102, in FaDuDD and SiHa cells,
      respectively, following three hours of tracer incubation. This was equal to or
      higher than ratios measured using the established hypoxia tracer [(18)F]FAZA.
      [(18)F]FPIMO also accumulated in tumors grown in mice, and reached tumor levels
      that were two to six-fold higher than in muscle three hours post-administration.
      Furthermore, the intra-tumoral distribution of [(18)F]FPIMO (autoradiography) and
      unlabeled pimonidazole (immunohistochemistry) was largely identical. Nonetheless,
      [(18)F]FPIMO proved inferior to [(18)F]FAZA, since absolute tumor signal and
      intra-tumoral contrast was low, thus compromising PET imaging. Low tumor signal
      was coupled to extensive tracer accumulation in liver and kidneys, and analysis
      of blood metabolites revealed that [(18)F]FPIMO was metabolized rapidly, with
      little parent compound remaining 15 minutes post-administration. Ongoing work
      focuses on the possibility of labeling pimonidazole in different positions with
      (18)F to improve tracer stability in vivo.

PMID- 23962244
TI  - Stereotactic body radiotherapy for small hepatocellular carcinoma: a
      retrospective outcome analysis in 185 patients.
AB  - BACKGROUND: Since 2005, we have treated hepatocellular carcinoma (HCC) with
      stereotactic body radiotherapy (SBRT) uniformly at two dose levels, according to
      baseline liver function and normal liver dose. We retrospectively examined the
      outcomes for these patients. MATERIAL AND METHODS: Between 2005 and 2012, 221 HCC
      patients were treated with SBRT. Eligibility criteria for SBRT included a single
      (either solitary or recurrent) HCC lesion; unfeasible, difficult or refusal to
      undergo other surgery or percutaneous ablative therapies; Child-Pugh
      Classification (CPC) A or B; tumors <= 5 cm; dose to the bowels < 25 Gy/5
      fractions; curative intent. Patients followed up >= 6 months were eligible. The
      prescribed dose depended on liver function and liver dose: 40 Gy for CPC-A and 35
      Gy for CPC-B, in 5 fractions, requiring a 5-Gy dose reduction if the proportion
      of the liver receiving >= 20 Gy exceeded 20%. Treatment outcomes and safety were
      analyzed. RESULTS: A total of 185 patients (n = 48 in the 35-Gy group; n = 137 in
      the 40-Gy group) were eligible, with a median follow-up duration of 24 months
      (range 3-80). The three-year local control and overall survival rates were 91%
      and 70%, respectively. There were no significant differences in outcomes between
      dose levels: the three-year local control and overall survival rates in the 35-Gy
      and 40-Gy groups were 91% and 89% (log-rank p = 0.99) and 66% and 72% (p = 0.54),
      respectively. Acute toxicities >= grade 3 were observed in 24 (13.0%) patients,
      and 19 (10.3%) patients had worsening of CPC score by two points. All but three
      (1.6%) patients promptly recovered to grade 1-2. Grade 5 liver failure occurred
      in two patients in the 35-Gy group. CONCLUSION: SBRT for HCC was safe and
      provided equivalent outcomes when administered either in 35 or 40 Gy/5 fractions.

PMID- 23962245
TI  - The future of microfluidics for biomarker detection.

PMID- 23962246
TI  - What are the recent advances in forensic oral fluid bioanalysis?

PMID- 23962249
TI  - Bioanalytical outsourcing: the two sides of the medal.

PMID- 23962250
TI  - Evaluation and subsequent minimization of matrix effects caused by phospholipids
      in LC-MS analysis of biological samples.
AB  - BACKGROUND: The influence of matrix effects in LC-MS/MS analysis of biological
      samples can be enormous and has to be evaluated during method development.
      Phospholipids, which are present in considerable quantities in biological fluids,
      are supposed to cause matrix effects when co-eluting with analytes. Therefore,
      the reduction of phospholipids should lead to the minimization of matrix effects.
      METHODOLOGY & RESULTS: Here, a polymeric reversed-phase (PRP) SPE cartridge was
      compared with a combination of mixed-mode-anion-exchange (MAX) and mixed-mode
      cation-exchange (MCX) SPE cartridges regarding elimination of matrix effects
      during sample clean-up. For evaluation of matrix effects post-column infusion
      experiments were performed. Phospholipid amount in the sample extract and matrix
      effects are enhanced using PRP in contrast to the combination of MAX/MCX.
      CONCLUSION: For an efficient elimination of phospholipids during sample
      preparation and to improve method accuracy and precision it is advisable to use a
      combination of MAX/MCX SPE cartridges.

PMID- 23962251
TI  - Identification of drug metabolites in human plasma or serum integrating
      metabolite prediction, LC-HRMS and untargeted data processing.
AB  - BACKGROUND: Comprehensive identification of human drug metabolites in first-in
      man studies is crucial to avoid delays in later stages of drug development. We
      developed an efficient workflow for systematic identification of human
      metabolites in plasma or serum that combines metabolite prediction, high
      resolution accurate mass LC-MS and MS vendor independent data processing.
      Retrospective evaluation of predictions for 14 (14)C-ADME studies published in
      the period 2007-January 2012 indicates that on average 90% of the major
      metabolites in human plasma can be identified by searching for accurate masses of
      predicted metabolites. Furthermore, the workflow can identify unexpected
      metabolites in the same processing run, by differential analysis of samples of
      drug-dosed subjects and (placebo-dosed, pre-dose or otherwise blank) control
      samples. To demonstrate the utility of the workflow we applied it to identify
      tamoxifen metabolites in serum of a breast cancer patient treated with tamoxifen.
      RESULTS & CONCLUSION: Previously published metabolites were confirmed in this
      study and additional metabolites were identified, two of which are discussed to
      illustrate the advantages of the workflow.

PMID- 23962252
TI  - Dried blood spots in bioanalysis of antimalarials: relevance and challenges in
      quantitative assessment of antimalarial drugs.
AB  - Malaria is the leading parasitic disease in emerging countries. Therapeutic drug
      monitoring of antimalarial drugs is becoming increasingly important due to their
      spreading resistance. Measuring systemic antimalarial drug concentrations is also
      vital for safety and PK evaluations during clinical development. The dried blood
      spot (DBS) technique is a convenient alternative sample-collection method to
      venipuncture, especially in resource -limited areas where the clinical studies of
      antimalarials are usually carried out. Various bioanalytical methods for
      antimalarial drug estimation utilizing DBS sampling have been reported. This
      review discusses the applicability and relevance of DBS in quantitative
      assessment of antimalarial drugs, the advantages and drawbacks of DBS, and the
      difficulties encountered during its implementation. 

PMID- 23962253
TI  - State-of-the-art dried blood spot analysis: an overview of recent advances and
      future trends.
AB  - Dried blood spots have become a popular method in a variety of micro blood
      sampling techniques in the life sciences sector, consequently competing with the
      field of conventional, invasive blood sampling by venepuncture. Dried blood spots
      are widely applied in numerous bioanalytical assays and have gained a significant
      role in the screening of inherited metabolic diseases, in PK and PD modeling; in
      the treatment and diagnosis of infectious diseases; and in therapeutic drug
      monitoring. Recent technological developments such as automation, online
      extraction, mass spectrometric direct analysis and also conventional dried blood
      spot bioanalysis, as well as future developments in dried blood spot bioanalysis
      are highlighted and presented in this article. 

PMID- 23962255
TI  - Evidence for past and present hybridization in three Antarctic icefish species
      provides new perspectives on an evolutionary radiation.
AB  - Determining the timing, extent and underlying causes of interspecific gene
      exchange during or following speciation is central to understanding species'
      evolution. Antarctic notothenioid fish, thanks to the acquisition of antifreeze
      glycoproteins during Oligocene transition to polar conditions, experienced a
      spectacular radiation to >100 species during Late Miocene cooling events. The
      impact of recent glacial cycles on this group is poorly known, but alternating
      warming and cooling periods may have affected species' distributions, promoted
      ecological divergence into recurrently opening niches and/or possibly brought
      allopatric species into contact. Using microsatellite markers and statistical
      methods including Approximate Bayesian Computation, we investigated genetic
      differentiation, hybridization and the possible influence of the last
      glaciation/deglaciation events in three icefish species of the genus Chionodraco.
      Our results provide strong evidence of contemporary and past introgression by
      showing that: (i) a substantial fraction of contemporary individuals in each
      species has mixed ancestry, (ii) evolutionary scenarios excluding hybridization
      or including it only in ancient times have small or zero posterior probabilities,
      (iii) the data support a scenario of interspecific gene flow associated with the
      two most recent interglacial periods. Glacial cycles might therefore have had a
      profound impact on the genetic composition of Antarctic fauna, as newly available
      shelf areas during the warmer intervals might have favoured secondary contacts
      and hybridization between diversified groups. If our findings are confirmed in
      other notothenioids, they offer new perspectives for understanding evolutionary
      dynamics of Antarctic fish and suggest a need for new predictions on the effects
      of global warming in this group. 

PMID- 23962256
TI  - Molecular mechanism underlying the antiproliferative effect of suppressor of
      cytokine signaling-1 in non-small-cell lung cancer cells.
AB  - Lung cancer (LC) is the major cause of death by cancer and the number of LC
      patients is increasing worldwide. This study investigated the therapeutic
      potential of gene delivery using suppressor of cytokine signaling 1 (SOCS-1), an
      endogenous inhibitor of intracellular signaling pathways, for the treatment of
      LC. To examine the antitumor effect of SOCS-1 overexpression on non-small-cell
      lung cancer (NSCLC) cells, NSCLC cells (A549, LU65, and PC9) were infected with
      adenovirus-expressing SOCS-1 vector. The cell proliferation assay showed that
      A549 and LU65, but not PC9, were sensitive to SOCS-1 gene-mediated suppression of
      cell growth. Although JAK inhibitor I could also inhibit proliferation of A549
      and LU65 cells, SOCS-1 gene delivery appeared to be more potent as SOCS-1 could
      suppress focal adhesion kinase and epidermal growth factor receptor, as well as
      the JAK/STAT3 signaling pathway. Enhanced phosphorylation of the p53 protein was
      detected by means of phospho-kinase array in SOCS-1 overexpressed A549 cells
      compared with control cells, whereas no phosphorylation of p53 was observed when
      JAK inhibitor I was used. Furthermore, treatment with adenoviral vector AdSOCS-1
      in vivo significantly suppressed NSCLC proliferation in a xenograft model. These
      results suggest that the overexpression of SOCS-1 gene is effective for antitumor
      therapy by suppressing the JAK/STAT, focal adhesion kinase, and epidermal growth
      factor receptor signaling pathways and enhancing p53-mediated antitumor activity
      in NSCLC. 

PMID- 23962257
TI  - Interstitial pregnancy management and subsequent pregnancy outcome.
AB  - We report on management and subsequent fertility outcome of interstitial
      pregnancy in a retrospective cohort study (Canadian Task Force classification II
      3) at a university affiliated teaching hospital. Of 706 women with extrauterine
      pregnancy, 14 consecutive women with interstitial pregnancy were treated by
      methotrexate, laparotomy or laparoscopy between 1997 and 2007. The first four
      women, with significant hemoperitoneum, were treated by laparotomy. Of the next
      10 women, four were selected for medical treatment with methotrexate. Only one
      case was treated successfully. The other six women had laparoscopic treatment. Of
      nine laparoscopies, one was converted to laparotomy due to excessive blood loss
      during the procedure. Of nine women desiring a child, three were infertile,
      whereas six conceived with an intrauterine pregnancy. A change from diagnosis
      later in pregnancy and laparotomy to more conservative treatment, mainly by
      laparoscopy, suggests a possibly better subsequent pregnancy rate. 

PMID- 23962258
TI  - Limited evidence for evolutionarily conserved targeting of long non-coding RNAs
      by microRNAs.
AB  - BACKGROUND: Long non-coding RNAs (lncRNAs) are emerging as important regulators
      of cell physiology, but it is yet unknown to what extent lncRNAs have evolved to
      be targeted by microRNAs. Comparative genomics has previously revealed widespread
      evolutionarily conserved microRNA targeting of protein-coding mRNAs, and here we
      applied a similar approach to lncRNAs. FINDINGS: We used a map of putative
      microRNA target sites in lncRNAs where site conservation was evaluated based on
      46 vertebrate species. We compared observed target site frequencies to those
      obtained with a random model, at variable prediction stringencies. While
      conserved sites were not present above random expectation in intergenic lncRNAs
      overall, we observed a marginal over-representation of highly conserved 8-mer
      sites in a small subset of cytoplasmic lncRNAs (12 sites in 8 lncRNAs at 56%
      false discovery rate, P = 0.10). CONCLUSIONS: Evolutionary conservation in
      lncRNAs is generally low but patch-wise high, and these patches could, in
      principle, harbor conserved target sites. However, while our analysis efficiently
      detected conserved targeting of mRNAs, it provided only limited and marginally
      significant support for conserved microRNA-lncRNA interactions. We conclude that
      conserved microRNA-lncRNA interactions could not be reliably detected with our
      methodology.

PMID- 23962260
TI  - A 42-year-old woman with a submammary intertrigo.

PMID- 23962259
TI  - TRialing individualized interventions to prevent functional decline in at-risk
      older adults (TRIIFL): study protocol for a randomized controlled trial nested in
      a longitudinal observational study.
AB  - BACKGROUND: Functional decline (FD) is a largely preventable feature of aging,
      characterized as gradual erosion of functional autonomy. This reduces an older
      person's capacity for safe, independent community living. The healthcare needs of
      an unprecedented aging population places pressure on health systems to develop
      innovative approaches to ensuring older people live healthy and independent lives
      for as long as possible. TRIIFL aims to demonstrate that: 1. Incipient FD in
      older people can be identified using a simple telephone-screening process within
      four weeks of discharge from an emergency department presentation for a minor
      health event; and 2. Early engagement into a person-centered individualized
      intervention arrests or reduces the rate of FD over the next 12 months.
      METHODS/DESIGN: A randomized controlled trial (RCT) nested within a 13-month
      longitudinal cohort study. The RCT (conducted over 12 months) tests the
      effectiveness of a novel, early, home-based, personalized program (compared with
      no intervention) in arresting or slowing FD. TRIIFL focuses on older adults
      living independently in the community, who have not yet had a serious health
      event, yet are potentially on the cusp of FD. Participants in the longitudinal
      cohort study will be recruited as they present to one large tertiary hospital
      Emergency Department, providing they are not subsequently admitted to a ward.
      Sample size calculations indicate that 570 participants need to be recruited into
      the longitudinal study, with 100 participants randomized into the trial arms.
      Measures from all subjects will be taken face-to-face at baseline (recruitment),
      then subsequently by telephone at one, four, seven and thirteen months later.
      Measures include functional abilities, quality of life, recent falls, mobility
      dependence, community supports and health service usage. Specific to the nested
      RCT, the quality of life tool (SF12) applied at one month, will identify
      individuals with low mental component quality of life scores, who will be invited
      to enter the RCT.Assessors will be blinded to RCT arm allocation, and subjects in
      the RCT will be blinded to the intervention being received by other subjects.
      TRIALS REGISTRATION: Australian & New Zealand Clinical Trials Registry:
      ACTRN12613000234718.

PMID- 23962261
TI  - Persistent erythematous linear plaque on left clavicular area.

PMID- 23962262
TI  - Does isotretinoin therapy of acne cure or cause depression?
AB  - Cosmetic defects in acne may provoke a wide range of mental disorders
      (depressive, social-phobic, etc.). Isotretinoin is a very effective acne
      treatment; hence, it usually resolves the associated mental disorders. However,
      more available data show the possible association of taking isotretinoin and the
      onset of a depressive syndrome that includes frank depression and even suicidal
      ideation. The frequency of depressive disorders during isotretinoin treatment
      varies from 1% to 11% in different studies, and it is unclear whether this is a
      consequence of isotretinoin therapy. Since it crosses the blood-brain barrier,
      isotretinoin affects the expression of a broad spectrum of genes in the limbic
      structures, thus affecting the function of the dopaminergic, serotonergic, and
      noradrenergic neurons involved in the regulation of mood and emotion. It was
      suggested that isotretinoin in high concentrations inhibits hippocampal
      neurogenesis and induces apoptosis of hippocampal cells. However, some studies do
      not confirm this pathogenic role, and isotretinoin was even reported to have a
      therapeutic effect in acne-associated depression. In this review, we highlight
      epidemiological data, the underlying molecular pathogenesis, and the aspects of
      prevention concerning retinoid-induced depression in acne from the practical
      point of view of a dermatologist. 

PMID- 23962263
TI  - Understanding efficacy end-points in studies of field-directed therapy for
      actinic keratosis.
AB  - BACKGROUND: The rates of short-term clearance of actinic keratoses appear to be
      comparable in clinical trials of topical treatments used in field therapy, but
      direct comparisons of efficacy results can be problematic. Trials use different
      efficacy end points, have different study designs, involve different anatomic
      sites, and enroll different patient populations. In addition, because adherence
      in real-world clinical practice differs from that observed in clinical trials,
      conclusions drawn from efficacy outcomes can be misleading. The objective of this
      review was to examine the efficacy end points used in studies of topical therapy
      for actinic keratosis, address other factors influencing efficacy outcomes in
      these studies, and discuss the possible influence of nonadherence on
      effectiveness. METHODS: Review of the available literature on topical therapy for
      actinic keratosis. RESULTS: The end points used to determine efficacy of
      therapies for actinic keratosis include a disparate group of outcomes, which can
      often make comparison between studies impossible. CONCLUSIONS: Efficacy end
      points of clinical studies designed to assess the treatment of actinic keratosis
      should be standardized to facilitate between-trial comparisons, and studies
      should focus on the end points that are most clinically relevant.

PMID- 23962264
TI  - Rapidly growing papular lesions on a giant congenital melanocytic nevus.

PMID- 23962265
TI  - The interrupted V-Y advancement flap for the reconstruction of the vulvovaginal
      defect.
AB  - BACKGROUND: High-quality reconstruction of vulvovaginal defects after tumor
      excision is critical. Various techniques for vulvovaginal reconstruction have
      been described. However, these flaps are often bulky, and tip necrosis
      occasionally occurs. To reduce bulkiness and prevent flap necrosis, we have
      therefore developed an ideal approach using a fasciocutaneous flap that is
      advanced in a modified V-Y fashion. MATERIALS AND METHODS: The V-Y flap is
      interrupted in the defect area by a bipedicled flap and therefore termed "the
      interrupted V-Y advancement flap". RESULTS: We used the interrupted V-Y
      advancement flap to cover vulvovaginal defects in five patients who underwent
      surgical treatment for extramammary Paget's disease or carcinoma of the vulva.
      Each flap survived completely without complications. CONCLUSIONS: This flap is
      easily elevated, not bulky, and reliable because it is supplied by the internal
      pudendal artery and vein without excessive skeletonization of the vascular
      pedicle; it also matches the local skin quality.

PMID- 23962266
TI  - Peripheral T cell lymphoma, not otherwise specified, showing multiple ulcers on
      the extremities.

PMID- 23962267
TI  - Paraneoplastic erythroderma: an unusual manifestation of diffuse large B-cell
      lymphoma.

PMID- 23962268
TI  - Ultrasonography detects symmetrical lividities of the soles of the feet: a non
      hyperhidrosis case treated with AlCl3 solution.

PMID- 23962270
TI  - In situ XRD study of La2Ni7H(x) during hydrogen absorption-desorption.
AB  - Structural changes of La2Ni7H(x) during the first and second absorption
      desorption processes along the P-C isotherm were investigated by in situ X-ray
      diffraction (XRD). Orthorhombic (Pbcn) and monoclinic (C2/c) hydrides coexisted
      in the first absorption plateau, but only a monoclinic (C2/c) hydride was
      observed in the first desorption plateau. Phase transformation of La2Ni7H(x) was
      irreversible between the first as well as the second absorption-desorption
      process. The lattice parameters and expansion of the La2Ni4 and LaNi5 cells
      during the absorption-desorption process were refined using the Rietveld method.
      The lattice parameters a and b of the orthorhombic hydride (Pbcn) decreased,
      while the lattice parameter c increased with increasing hydrogen content in the
      first absorption. During the first absorption, the volume of the orthorhombic
      La2Ni4 cell expanded by more than 50%, while the expansion of the LaNi5 cell was
      below 10%. The monoclinic La2Ni4 cell expanded to approximately four times the
      size of the LaNi5 cell in the first absorption. The lattice parameters a, b, and
      c of the monoclinic hydride (C2/c) decreased with decreasing hydrogen content in
      the first desorption. These La2Ni4 and LaNi5 cells contracted isotropically in
      the first desorption.

PMID- 23962271
TI  - Formation of highly substituted tetrahydropyranones: application to the total
      synthesis of cyanolide A.
AB  - A new tetrahydropyranone synthesis has been developed that leads to cis-2,6
      disubstituted 3,3-dimethyltetrahydropyran-4-one rings by condensation of an
      aldehyde and a hydroxy silyl enol ether. The reaction works with a variety of
      aldehydes to produce the tetrahydropyranone products in moderate to high yields.
      This new method was applied to the enantioselective synthesis of cyanolide A and
      its aglycone. 

PMID- 23962272
TI  - Development of large band-gap conjugated copolymers for efficient regular single
      and tandem organic solar cells.
AB  - We demonstrated the synthesis and characterization of two conjugated copolymers,
      PBDTFBZO and PBDTFBZS, consisting of dialkylthiol substituted benzo[1,2-b:4,5
      b']dithiophene donor and monofluorinated benzotriazole acceptor blocks. The
      resulting copolymers show large band gaps, deep HOMO and LUMO energy levels.
      Improved V(oc), J(sc), and FF were obtained at the same time to increase overall
      efficiencies of their single and tandem polymer solar cells. The enhanced V(oc)
      can be ascribed to a low-lying HOMO energy level by incorporating dialkylthiol
      and fluorine substituents on the polymer backbone. The improvement in J(sc) and
      FF are likely due to high carrier mobility, suppressed charge recombination, and
      fine nanostructure morphology. A 7.74% PCE was achieved from the regular single
      device based on PBDTFBZS:PC71BM blend film with 3% 1,8-diiodooctane (DIO)
      additive. In combination with low band gap diketopyrrolopyrrole (DPP)-based
      copolymer, tandem devices based on PBDTFBZS exhibited high PCE up to 9.40%. The
      results indicate that PBDTFBZO and PBDTFBZS are promising polymer donor materials
      for future application of large-area polymer solar cells.

PMID- 23962273
TI  - Clinical associations with uterine tachysystole.
AB  - OBJECTIVES: To determine the incidence of uterine tachysystole (UT) and its
      association with neonatal depression or metabolic acidemia (DEP). METHODS: This
      retrospective study comprised all 6234 women at >= 37 weeks' gestation who were
      monitored during the last 4 hours of tracings before birth in an academic
      community hospital. DEP was defined by an umbilical artery base deficit value >=
      10 mmol/L or a 5-minute Apgar <= 6 and included 77 births. UT was defined by >15
      contractions in 30 minutes. RESULTS: The overall incidence of UT was 18.3%
      (1139/6234). In 4.2% (260/6234) UT persisted for >60 min. The rate of UT was
      similar in births with DEP (14.3%, 11/77) compared to those without DEP (18.3%,
      1128/6157; p=0.45). In births with UT, only 1.0% (11/1139) developed DEP. The DEP
      group had more decelerations at almost every level of contractions and a higher
      cesarean rate of 49.4% (38/77) compared to 24.0% (1468/6124); p=<0.001 in the
      group without DEP. CONCLUSIONS: UT was common, occasionally prolonged and almost
      always benign. Fetuses with DEP had no more UT than those without DEP. Many
      babies with DEP declared their vulnerability with decelerations at contraction
      rates below UT levels and the great majority of them never experienced UT.

PMID- 23962274
TI  - Poly(L-lactic acid) crystallization in a confined space containing graphene oxide
      nanosheets.
AB  - The semicrystalline polymer incorporated with nanofillers frequently exhibits
      complicated crystallization behavior, which is probably attributed to the
      nanofiller-constructed complex crystalline circumstance, especially a confined
      space. In the present work, in order to have a thorough understanding of
      biodegradable poly(L-lactic acid) (PLLA) crystallization behavior on the
      dependence of graphene oxide nanosheet (GONS) loadings, in particular the
      relatively high GONS loading, a set of GONS/PLLA nanocomposites with different
      GONS loadings ranging from 0 to 4.0 wt % were investigated in terms of isothermal
      crystallization behavior by differential scanning calorimetry and time-resolved
      Fourier-transform infrared spectroscopy techniques. The results indicated that
      GONSs not only served as heterogeneous nucleating agents for PLLA crystallization
      but also restricted the mobility and diffusion of PLLA chains. At low GONS
      concentrations of 0.25 and 0.5 wt %, GONSs acted as a temple for PLLA chains to
      land on due to extremely high specific surface area, thus promoting the
      conformational ordering and reducing the nucleating barrier. The nucleation
      effect of GONSs was dominant to achieve accelerated overall crystallization
      kinetics. As the GONS concentration rose up to 1.0 wt %, the GONS network was
      formed in the PLLA matrix, which was verified by solid-like rheological behavior
      at low frequencies in rheological measurement. The nanofiller network
      significantly constrained the mobility and diffusion of PLLA chains and offset
      the nucleation effect of GONSs, giving rise to a turning point in crystallization
      rate from promotion to restriction. Furthermore, a severely confined space was
      constructed by the more crowded and denser GONS networks at a higher GONS
      concentration of 4.0 wt %, compelling PLLA lamellae to grow in a two-dimensional
      mode. The unusual crystallization behavior of PLLA from promotion to restriction
      was also understood by the four-region model, in which the semiquantitative
      description of crystalline circumstance was provided. These results pave an
      effective way to further reveal the crystallization behavior of polymer at a
      relatively high nanofiller loading.

PMID- 23962275
TI  - Voting with their feet--predictors of discharge against medical advice in
      Aboriginal and non-Aboriginal ischaemic heart disease inpatients in Western
      Australia: an analytic study using data linkage.
AB  - BACKGROUND: Discharge Against Medical Advice (DAMA) from hospital is associated
      with adverse outcomes and is considered an indicator of the responsiveness of
      hospitals to the needs of Aboriginal and Torres Strait Islander Australians, the
      indigenous people of Australia. We investigated demographic and clinical factors
      that predict DAMA in patients experiencing their first-ever inpatient admission
      for ischaemic heart disease (IHD). The study focuses particularly on the
      differences in the risk of DAMA in Aboriginal and non-Aboriginal patients while
      also investigating other factors in their own right. METHODS: A cross-sectional
      analytical study was undertaken using linked hospital and mortality data with
      complete coverage of Western Australia. Participants included all first-ever IHD
      inpatients (aged 25-79 years) admitted between 2005 and 2009, selected after a 15
      year clearance period and who were discharged alive. The main outcome measure was
      DAMA as reflected in the hospital record.Multiple logistic regression was used to
      determine disparities in DAMA between Aboriginal and non-Aboriginal patients,
      adjusting for a range of demographic and clinical factors, including comorbidity
      based on 5-year hospitalization history. A series of additional models were run
      on subgroups of the cohort to refine the analysis. Ethics approval was granted by
      the WA Human Research and the WA Aboriginal Health Ethics Committees. RESULTS:
      Aboriginal patients comprised 4.3% of the cohort of 37,304 IHD patients and 23%
      of the 224 DAMAs. Emergency admission (OR=5.9, 95% CI 2.9-12.2), alcohol
      admission history (alcohol-related OR=2.9, 95% CI 2.0-4.2) and Aboriginality (OR
      2.3, 95% CI 1.5-3.5) were the strongest predictors of DAMA in the multivariate
      model. Patients living in rural areas while attending non-metropolitan hospitals
      had a 50% higher risk of DAMA than those living and hospitalised in metropolitan
      areas. There was consistency in the ORs for Aboriginality in the different
      multivariate models using restricted sub-cohorts and different Aboriginal
      identifiers. Sex, IHD diagnosis type and co-morbidity scores imparted different
      risks in Aboriginal versus non-Aboriginal patients. CONCLUSIONS: Understanding
      the risks and reasons for DAMA is important for health system policy and
      proactive management of those at risk of DAMA. Improving care to prevent DAMA
      should target unplanned admissions, rural hospitals and young men, Aboriginal
      people and those with alcohol and mental health comorbidities.

PMID- 23962276
TI  - Temporal variation of residential pesticide use and comparison of two survey
      platforms: a longitudinal study among households with young children in Northern
      California.
AB  - BACKGROUND: Pesticide use patterns are essential inputs into human pesticide
      exposure models. Currently, data included for modeling purposes have mostly been
      collected in cross-sectional surveys. However, it is questionable whether
      responses to one-time surveys are representative of pesticide use over longer
      periods, which is needed for assessment of health impact. This study was designed
      to evaluate population-wide temporal variations and within-household variations
      in reported residential pesticide use patterns and to compare alternative
      pesticide data collection methods - web surveys versus telephone interviews.
      METHOD: A total of 481 households in Northern California provided up to 3 annual
      telephone interviews on residential pesticide use; 182 of these households
      provided up to 6 quarterly web surveys that covered the same topics for some of
      the same time periods. Information on frequency and areas of application were
      collected for outdoor and indoor sprays, indoor foggers, professional
      applications, and behind-the-neck treatments for pets. Population-wide temporal
      variation and within-household consistency were examined both within telephone
      surveys and within web surveys, and quantified using Generalized Estimating
      Equations and Mixed Effect Modeling. Reporting between the two methods, the
      telephone survey and the web survey, was also compared. RESULTS: Use prevalence
      of outdoor sprays across the population reported in both the annual telephone
      surveys and the quarterly web surveys decreased over time, as did behind-the-neck
      treatment of pets reported in the quarterly web survey. Similarly, frequencies of
      use of these products decreased in the quarterly web surveys. Indoor sprays
      showed no statistically significant population-wide temporal variation in either
      survey. Intraclass correlation coefficients indicated consistent use within a
      household for behind-the-neck treatment on pets and outdoor sprays but great
      variability for the use of indoor sprays. Indoor sprays were most consistently
      applied in the bathroom and kitchen. Outdoor sprays were consistently more often
      applied by male household members, while indoor sprays were not. The two survey
      approaches obtained fairly similar results on the prevalence of using pesticides,
      but found discrepancies in use frequencies. In addition, the number of products
      purchased was positively correlated with application frequency for outdoor sprays
      (R = 0.51, p = 0.0005) but not for indoor sprays. CONCLUSIONS: In this
      population, repeated surveys are necessary either to obtain a reliable estimate
      of the average household use of pesticides or to project potential temporal
      changes of pesticide use. Web surveys could collect comparable data to
      traditional telephone surveys for some information. However, researchers need to
      consider the internet acceptability among the target population and balance lower
      participant burden against the need for sufficiently accurate time-varying
      measurement, to improve subject retention in longitudinal surveys.

PMID- 23962277
TI  - Cardiolipin effects on membrane structure and dynamics.
AB  - Cardiolipin (CL) is a lipid with unique properties solely found in membranes
      generating electrochemical potential. It contains four acyl chains and tends to
      form nonlamellar structures, which are believed to play a key role in membrane
      structure and function. Indeed, CL alterations have been linked to disorders such
      as Barth syndrome and Parkinson's disease. However, the molecular effects of CL
      on membrane organization remain poorly understood. Here, we investigated the
      structure and physical properties of CL-containing membranes using confocal
      microscopy, fluorescence correlation spectroscopy, and atomic force microscopy.
      We found that the fluidity of the lipid bilayer increased and its mechanical
      stability decreased with CL concentration, indicating that CL decreases the
      packing of the membrane. Although the presence of up to 20% CL gave rise to flat,
      stable bilayers, the inclusion of 5% CL promoted the formation of flowerlike
      domains that grew with time. Surprisingly, we often observed two membrane
      piercing events in atomic force spectroscopy experiments with CL-containing
      membranes. Similar behavior was observed with a lipid mixture mimicking the
      mitochondrial outer membrane composition. This suggests that CL promotes the
      formation of membrane areas with apposed double bilayers or nonlamellar
      structures, similar to those proposed for mitochondrial contact sites. All
      together, we show that CL induces membrane alterations that support the role of
      CL in facilitating bilayer structure remodeling, deformation, and
      permeabilization. 

PMID- 23962278
TI  - Improving the therapeutic efficiency of ginger extract for treatment of colon
      cancer using a suitably designed multiparticulate system.
AB  - Ginger extract (GE), a potential natural anticancer agent, has compromised
      therapeutic utilization due to poor bioavailability and physicochemical
      properties. Present study aimed at assigning GE with a pharmaceutical couture so
      as to improve its biopharmaceutical performance by monitoring its localized
      (though prolonged) delivery in the distal parts of gastrointestinal tract for the
      treatment of colon cancer. Alginate beads entrapping 85.9 +/- 1.78% GE were
      subjected to Eudragit S100 coating. Latter is insoluble at acidic and near
      neutral (6.8) pH of stomach and upper part of small intestine and it led to 50%
      retardation (upto 12 h) in release of GE. However, it was solubilised at pH > 7.0
      resulting in colon targeted system. Developed beads were free flowing, showed a
      particle size of 0.9 +/- 0.006 mm and super class-II release controlled by
      swelling and polymer relaxation. Preclinical evaluation using 1,2
      dimethylhydrazine-induced colon cancer, in male Wistar rats, in terms of
      histopathology, oxidative stress, mitochondrial complex activity, beta
      glucuronidase and ammonia concentration determinations indicated GE loaded beads
      (50 mg/kg) to be significantly better (p < 0.05) than free GE. Highlight of the
      study was that GE loaded coated alginate beads were administered after the
      induction of colon cancer and significant recession of the cancers was observed
      after 4 weeks of treatment.

PMID- 23962280
TI  - Natural polypeptide-based supramolecular nanogels for stable noncovalent
      encapsulation.
AB  - Supramolecular nanogel, a physically cross-linked nanosize hydrogel,
      spontaneously self-assembles in aqueous solution via secondary interactions and
      is thus of great interest in nanomedicine as a drug carrier. We developed a
      versatile method for supramolecular nanogel self-assembled by electrostatic
      interaction between positive surfactant micelles and negative polypeptides. Core
      shell-like structures of supramolecular nanogels provide stable hydrophobic
      pockets that prevent simple diffusion of hydrophobic guest molecules, resulting
      in high encapsulation stability. The size of the supramolecular nanogels can be
      systematically controlled by varying the size of the surfactant micelles.
      Furthermore, noncovalently encapsulated dye molecules can be released in response
      to matrix metalloproteinases highly overexpressed in tumor tissues, potentially
      providing tumor-triggered targeting. 

PMID- 23962279
TI  - Implementation of TPMT testing.
AB  - The activity of the enzyme thiopurine methyltransferase (TPMT) is regulated by a
      common genetic polymorphism. One in 300 individuals lack enzyme activity and 11%
      are heterozygous for a variant low activity allele and have an intermediate
      activity. The thiopurine drugs azathioprine, mercaptopurine and thioguanine are
      substrates for TPMT; these drugs exhibit well documented myelosuppressive effects
      on haematopoietic cells and have a track record of idiosyncratic drug reactions.
      The development of severe bone marrow toxicity, in patients taking standard doses
      of thiopurine drugs, is associated with TPMT deficiency whilst the TPMT
      heterozygote is at an increased risk of developing myelosuppression. Factors
      influencing TPMT enzyme activity, as measured in the surrogate red blood cell,
      are discussed in this review to enable an appreciation of why concordance between
      TPMT genotype and phenotype is not 100%. This is particularly important for
      lower/intermediate TPMT activities to avoid misclassification of TPMT status.
      TPMT testing is now widely available in routine service laboratories. The British
      National Formulary suggests TPMT testing before starting thiopurine drugs.
      Dermatologists were quick to adopt routine TPMT testing whilst
      gastroenterologists do not specifically recommend TPMT screening. TPMT testing is
      mandatory prior to the use of mercaptopurine in childhood leukaemia. Thiopurine
      drug dose and other treatment related influences on cell counts explain some of
      the differing recommendations between clinical specialities. TPMT testing is cost
      effective and the major role is in the identification of the TPMT deficient
      individual prior to the start of thiopurine drugs. 

PMID- 23962281
TI  - Hierarchical Bayesian modelling of gene expression time series across irregularly
      sampled replicates and clusters.
AB  - BACKGROUND: Time course data from microarrays and high-throughput sequencing
      experiments require simple, computationally efficient and powerful statistical
      models to extract meaningful biological signal, and for tasks such as data fusion
      and clustering. Existing methodologies fail to capture either the temporal or
      replicated nature of the experiments, and often impose constraints on the data
      collection process, such as regularly spaced samples, or similar sampling schema
      across replications. RESULTS: We propose hierarchical Gaussian processes as a
      general model of gene expression time-series, with application to a variety of
      problems. In particular, we illustrate the method's capacity for missing data
      imputation, data fusion and clustering.The method can impute data which is
      missing both systematically and at random: in a hold-out test on real data,
      performance is significantly better than commonly used imputation methods. The
      method's ability to model inter- and intra-cluster variance leads to more
      biologically meaningful clusters. The approach removes the necessity for evenly
      spaced samples, an advantage illustrated on a developmental Drosophila dataset
      with irregular replications. CONCLUSION: The hierarchical Gaussian process model
      provides an excellent statistical basis for several gene-expression time-series
      tasks. It has only a few additional parameters over a regular GP, has negligible
      additional complexity, is easily implemented and can be integrated into several
      existing algorithms. Our experiments were implemented in python, and are
      available from the authors' website:
      http://staffwww.dcs.shef.ac.uk/people/J.Hensman/.

PMID- 23962282
TI  - Construction of KHV-CJ ORF25 DNA vaccine and immune challenge test.
AB  - KHV ORF25 fragments were cloned from Koi Herpes Virus-CJ (KHV-CJ) strains
      isolated in our laboratory. The amplified products were inserted into the
      eukaryotic expression vector pIRES-neo, forming recombinant plasmid pIRES-ORF25.
      The recombinant plasmid pIRES-ORF25 at 1 MUg per koi, 10 MUg per koi and 50 MUg
      per koi was intramuscularly injected into healthy kois, respectively. The results
      showed that the recombinant pIRES-ORF25 could induce the production of specific
      antibodies in koi determined by indirect ELISA. The differences of immune effect
      between three doses were not significant (P > 0.05), but all of them could induce
      the production of neutralizing antibodies. The immune challenge test showed that
      the mortality of koi injected with PBS, blank pIRES-neo vector and nothing was
      90%, 92.5% and 85% at 25 days. While the mortalities of koi injected with
      eukaryotic expression plasmid pIRES-ORF25 were 20%, 17.5% and 12.5%. Differences
      in comparison with the control group were highly significant (P < 0.01).
      Histopathological staining revealed that the tissues of the immunized koi did not
      change apparently. In conclusion, the DNA vaccine pIRES-ORF25 construct could
      well protect koi against KHV and had the potential to be applied in practice. 

PMID- 23962283
TI  - Acceptance of the 2013 Henry Baldwin ward medal: standing on the shoulders of
      benevolent giants.

PMID- 23962285
TI  - Perception of size of movement patterns.
AB  - Physiological data suggest that perception and memory of kinesthesis may differ
      depending on whether a movement pattern is actively commanded or passively
      induced. An attempt was made to demonstrate a difference between these two types
      of movements by employing a cross-modal visual recognition test of size
      perception. Absolute and algebraic errors in the matching of kinesthesis with
      vision were measured. Positive algebraic errors were seen indicating that
      subjects' perception for the size of kinesthetic movement patterns was magnified
      as compared to vision. Active kinesthesis was matched with vision more accurately
      than was passive kinesthesis, and the data yielded information about the
      differential contribution of active and passive muscle compartments to the global
      kinesthetic perception of voluntary movement. Cross-modal matching of kinesthesis
      with vision was in certain cases as accurate as visual intramodal matching. It
      was argued that active kinesthesis has internal references, and vision has
      external references to facilitate the similar-size recognition performance. 

PMID- 23962284
TI  - The Schizosaccharomyces pombe fusion gene hal3 encodes three distinct activities.
AB  - Saccharomyces cerevisiae Hal3 and Vhs3 are moonlighting proteins, forming an
      atypical heterotrimeric decarboxylase (PPCDC) required for CoA biosynthesis, and
      regulating cation homeostasis by inhibition of the Ppz1 phosphatase. The
      Schizosaccharomyces pombe ORF SPAC15E1.04 (renamed as Sp hal3) encodes a protein
      whose amino-terminal half is similar to Sc Hal3 whereas its carboxyl-terminal
      half is related to thymidylate synthase (TS). We show that Sp Hal3 and/or its N
      terminal domain retain the ability to bind to and modestly inhibit in vitro S.
      cerevisiae Ppz1 as well as its S. pombe homolog Pzh1, and also exhibit PPCDC
      activity in vitro and provide PPCDC function in vivo, indicating that Sp Hal3 is
      a monogenic PPCDC in fission yeast. Whereas the Sp Hal3 N-terminal domain
      partially mimics Sc Hal3 functions, the entire protein and its carboxyl-terminal
      domain rescue the S. cerevisiae cdc21 mutant, thus proving TS function.
      Additionally, we show that the 70 kDa Sp Hal3 protein is not proteolytically
      processed under diverse forms of stress and that, as predicted, Sp hal3 is an
      essential gene. Therefore, Sp hal3 represents a fusion event that joined three
      different functional activities in the same gene. The possible advantage derived
      from this surprising combination of essential proteins is discussed. 

PMID- 23962286
TI  - A reappraisal of fitts' law.
AB  - This paper presents a reappraisal of Fitts' (1954) law and outlines reasoning
      which predicts that, for tasks of equivalent difficulty as calculated by Fitts'
      Index of Difficulty, smaller-tolerance tasks will, within limits, take longer to
      perform. Reanalysis of Fitts' data appears to confirm this view. The notion that
      the overall performance of the human motor system plus associated feedback
      mechanisms can be described by any simple formulation assuming constant weighting
      of factors over a variety of tasks, such as proposed by Fitts' law, seems to be
      misfounded. Recent research supports the doubts concerning fixed-parameter linear
      and nonlinear models of the human motor system. Some implications of these ideas
      are discussed. 

PMID- 23962287
TI  - Spatial-temporal analysis of movements in children.
AB  - Hand-eye coordination was studied in 5-, 7-, 9-, and 11-yr-old children in order
      to test the hypothesis of an evolution in the relationship between the
      programming system and the guidance system in reaching movement. In the first
      experiment children had to perform open-loop movements (i.e., without seeing
      their hands towards visual targets as accurately as possible. The accuracy, time,
      speed, and patterns of movements were analyze second experiment the reach
      trajectories of the hand were analyzed in children wearing displacing prisms in
      order to measure the visually guided part of the trajectory. Charges in the
      spatial-temporal characteristics of open-loop reaching movements and in the
      amount of visual guided activity appear from the results. A predominance the
      programming system at 5 yr and guiding system at 7 yr, followed at 9 11 yr by
      integration of both systems, is discussed. 

PMID- 23962288
TI  - Memory for constrained and preselected movement location and distance.
AB  - These experiments assessed the interrelationship between location and distance
      cues in the coding of movements. In separate experiments subjects recalled either
      the terminal location or the distance of constrained (Experiment 1) or
      preselected (Experiment 2) movements following a 15-sec retention interval.
      Changes in direction amd amplitude of starting position were used to ascertain
      whether recall errors were related to these changes. The findings of both
      experiments indicated that location and distance were recalled with similar
      accuracy when the starting position was identical for the criterion and recall
      movement. However, analysis of constant errors when the recall starting position
      was varied in either direction clearly indicated neither terminal location nor
      distance are coded independently, and memory for movement is based on an
      interaction between these cues. 

PMID- 23962289
TI  - The effects of expectancy and previous task cues on motor performance.
AB  - The effects of manipulated outcome expectancies (success/failure) and manipulated
      previous task cues (similar/dissimilar) on motor performance were investigated.
      Female collegiate students (n=60) were randomly placed into one of four treatment
      conditions: (a) success/similar task, (b) success/dissimilar task, (c)
      failure/similar task, (d) failure/dissimilartask. The manipulated information was
      provided after performance on a pursuit rotor task; subjects then performed on a
      second task (stabilometer). Data were analyzed by a 2x2x4 factorial ANOVA with
      repeated measures on the last factor. Subjects who experienced the high
      expectancy treatment performed significantly better than subjects who experienced
      the low-expectancy treatment as the performance pattern developed over time.
      Although the findings only partially supported the predictions generated by self
      enhancement theory, this theory appeared to have greater explanatory power than
      consistency theory. 

PMID- 23962290
TI  - The significance of nonsignificant findings.
AB  - The replication by Landers et al. (1978) of the Martens' (1969) social
      facilitation study is evaluated. The atypical constant error (CE) performance
      curve obtained in the Martens' study may diminish the external validity of the CE
      results, but not the internal validity. Furthermore, the validity of the AE
      results as well as the highly significant physiological corroborative data remain
      unscathed. Finally, the conclusions about social facilitation research reached by
      Landers et al. are questioned in light of their nonsignificant, noncorroborated,
      and statistically nonpowerful results. 

PMID- 23962291
TI  - The significance of "significant" results.
AB  - Based upon new analyses we have performed, Martens' (1969) CE data are shown to
      lack both internal and external validity. Also, compared to other PSI techniques,
      the chemical mixture used in Martens' study and our (1978) study is shown to
      produce prints of inconsistent quality. 

PMID- 23962292
TI  - Enhanced antitumor efficacy of fiber-modified, midkine promoter-regulated
      oncolytic adenovirus in human malignant mesothelioma.
AB  - Oncolytic virotherapy using adenoviruses has potential for therapeutic benefits
      in malignant mesothelioma. However, the downregulation of coxsackie
      virus/adenovirus receptor (CAR) expression is frequently a critical rate-limiting
      factor that impedes the effectiveness of adenovirus serotype 5 (Ad5)-based
      vectors in many cancer types. We evaluated CAR (Ad5 receptor) and CD46
      (adenovirus serotype 35 [Ad35] receptor) expression in six human malignant
      mesothelioma cell lines. Very low CAR expression was observed in MSTO-211H and
      NCI-H2052 cells, whereas the other cell lines showed strong expression. In
      contrast, CD46 was highly expressed in all mesothelioma cell lines. On this
      basis, we replaced the CAR binding sequence of Ad5 with the CD46 binding sequence
      of Ad35 in the replication-defective adenoviruses and the tumor-specific midkine
      promoter-regulated oncolytic adenoviruses. By this fiber modification, the
      infectivity, virus progeny production, and in vitro cytocidal effects of the
      adenoviruses were significantly enhanced in low CAR-expressing MSTO-211H and NCI
      H2052 cells, also resulting in similar or even higher levels in high CAR
      expressing mesothelioma cell lines. In MSTO-211H xenograft models, the fiber
      modified oncolytic adenovirus significantly enhanced antitumor effect compared to
      its equivalent Ad5-based vector. Our data demonstrate that Ad35 fiber
      modification of binding tropism in a midkine promoter-regulated oncolytic Ad5
      vector confers transductional targeting to oncolytic adenoviruses, thereby
      facilitating more effective treatment of malignant mesothelioma. 

PMID- 23962293
TI  - 2012 trends and statistics for prescription medications in the United States: CNS
      therapeutics continue to hold leading positions.

PMID- 23962295
TI  - The apoptosis-inducing effect of ginsenoside F4 from steamed notoginseng on human
      lymphocytoma JK cells.
AB  - In this study, the inhibitory and apoptosis-inducing effect of ginsenoside F4
      (GF4) from steamed notoginseng was investigated by using human lymphocytoma
      Jurkat (JK) cell. Cell Counting Kit-8 method was then used to assess the anti
      proliferative effect of GF4, and Western blotting was run to detect the
      expression level of two apoptosis-related proteins including Bax and the Bcl-2.
      The results suggested that GF4 can effectively inhibit the proliferation of the
      cells, and Bax expression increased gradually, but Bcl-2 expression reduced with
      the increase of GF4 concentration. In conclusion, GF4 has inhibitory effect on
      human lymphocytoma JK cell by inducing its apoptosis. The mechanism of action
      could be related to the mitochondrial dysfunction and the increase of Bax
      expression and decrease of Bcl-2 expression by GF4. 

PMID- 23962296
TI  - 25-(OH)VitD3, as a risk indicator in diagnosis of adenocarcinoma.
AB  - Vitamin D (VitD) comes from sunlight exposure and food intake. Apart from
      regulating calcium homeostasis and bone function, its levels also associate with
      the presence of development of adenocarcinoma. VitD can interact with VitD
      receptor (VDR), which heterodimerizes with retinoic X receptor (RXR) and then
      induces transcription of proteins that function in cell proliferation,
      differentiation, apoptosis, and angiogenesis. We reviewed and discussed the genes
      and their associated polymorphisms involved in the correlation between
      development of adenocarcinoma and VitD deficiency to highlight how VitD may be
      instrumental in cancerization. Furthermore, pilot epidemiological data show that
      the detection of 25-hydroxy-Vitamin D3 ((36.5+/-10.7 nmol/L, n=129) vs (81.4+/
      19.8 nmol/L, n=81)) can be a promising approach in cancer diagnosis. In this
      review, we suggest that 25-hydroxy-Vitamin D3 can act as an indicator and/or risk
      assessment factor in early diagnosis, prognosis and treatment of adenocarcinoma. 

PMID- 23962298
TI  - Use of weeds as traditional vegetables in Shurugwi District, Zimbabwe.
AB  - BACKGROUND: Most agricultural weeds are usually regarded as undesirable and
      targeted for eradication. However, weeds are useful to human beings as food and
      traditional medicines. Few studies have been done to document the uses of weeds
      as traditional vegetables. This study was therefore, done to document indigenous
      knowledge related to the diversity and use of agricultural weeds as traditional
      vegetables in Shurugwi District, Zimbabwe, emphasizing their role in food
      security and livelihoods of the local people. MATERIALS AND METHODS: Semi
      structured interviews, observation and guided field walks with 147 participants
      were employed between December 2011 and January 2012 to obtain ethnobotanical
      data on the use of edible weeds as traditional vegetables. Based on
      ethnobotanical information provided by the participants, botanical specimens were
      collected, numbered, pressed and dried for identification. RESULTS: A total of 21
      edible weeds belonging to 11 families and 15 genera, mostly from Amaranthaceae
      (19%), Asteraceae and Tiliaceae (14.3%), Capparaceae, Cucurbitaceae and
      Solanaceae (9.5% each) were identified. Of the documented edible weeds, 52.4% are
      indigenous while 47.6% are exotic to Zimbabwe; either semi-cultivated or growing
      naturally as agricultural weeds in farmlands, fallow land and home gardens. Among
      the main uses of edible weeds were leafy vegetables (81%), followed by edible
      fruits (19%), edible corms (9.5%), edible flowers and seeds (4.8% each). The most
      important edible weeds were Cleome gynandra, cited by 93.9% of the participants,
      Cucumis metuliferus (90.5%), Cucumis anguria (87.8%), Corchorus tridens (50.3%)
      and Amaranthus hybridus (39.5%). All edible weeds were available during rainy and
      harvest period with Cleome gynandra, Corchorus tridens, Cucumis anguria, Cucumis
      metuliferus and Moringa oleifera also available during the dry season, enabling
      households to obtain food outputs in different times of the year. The importance
      of edible weeds for local livelihoods was ubiquitously perceived, with all
      participants reporting their contribution towards food security and nutrition.
      CONCLUSION: The present study confirm findings from similar studies conducted
      elsewhere that rural households engage in harvesting of wild edible vegetables
      and other non-timber forest products (NTFPs) as a survival strategy. Based on
      their potential nutritional and medicinal value, edible weeds could contribute in
      a major way to food security, basic primary health care and balanced diets of
      rural households and possibly urban households as well.

PMID- 23962299
TI  - Prediction of aquatic toxicity mode of action using linear discriminant and
      random forest models.
AB  - The ability to determine the mode of action (MOA) for a diverse group of
      chemicals is a critical part of ecological risk assessment and chemical
      regulation. However, existing MOA assignment approaches in ecotoxicology have
      been limited to a relatively few MOAs, have high uncertainty, or rely on
      professional judgment. In this study, machine based learning algorithms (linear
      discriminant analysis and random forest) were used to develop models for
      assigning aquatic toxicity MOA. These methods were selected since they have been
      shown to be able to correlate diverse data sets and provide an indication of the
      most important descriptors. A data set of MOA assignments for 924 chemicals was
      developed using a combination of high confidence assignments, international
      consensus classifications, ASTER (ASessment Tools for the Evaluation of Risk)
      predictions, and weight of evidence professional judgment based an assessment of
      structure and literature information. The overall data set was randomly divided
      into a training set (75%) and a validation set (25%) and then used to develop
      linear discriminant analysis (LDA) and random forest (RF) MOA assignment models.
      The LDA and RF models had high internal concordance and specificity and were able
      to produce overall prediction accuracies ranging from 84.5 to 87.7% for the
      validation set. These results demonstrate that computational chemistry approaches
      can be used to determine the acute toxicity MOAs across a large range of
      structures and mechanisms. 

PMID- 23962297
TI  - Dementia in Down's syndrome: an MRI comparison with Alzheimer's disease in the
      general population.
AB  - BACKGROUND: Down's syndrome (DS) is the most common genetic cause of intellectual
      disability. People with DS are at an increased risk of Alzheimer's disease (AD)
      compared to the general population. Neuroimaging studies of AD have focused on
      medial temporal structures; however, to our knowledge, no in vivo case-control
      study exists comparing the anatomy of dementia in DS to people with AD in the
      general population. We therefore compared the in vivo brain anatomy of people
      with DS and dementia (DS+) to those with AD in the general population. METHOD:
      Using MRI in 192 adults, we compared the volume of whole brain matter, lateral
      ventricles, temporal lobes and hippocampus in DS subjects with and without
      dementia (DS+, DS-), to each other and to three non-DS groups. These included one
      group of individuals with AD and two groups of controls (each age-matched for
      their respective DS and general population AD cohorts). RESULTS: AD and DS+
      subjects showed significant reductions in the volume of the whole brain,
      hippocampus and temporal lobes and a significant elevation in the volume of the
      lateral ventricle, compared to their non-demented counterparts. People with DS+
      had a smaller reduction in temporal lobe volume compared to individuals with AD.
      CONCLUSIONS: DS+ and AD subjects have a significant reduction in volume of the
      same brain regions. We found preliminary evidence that DS individuals may be more
      sensitive to tissue loss than others and have less 'cognitive reserve'.

PMID- 23962300
TI  - Trisequential photooxygenation reaction: application to the synthesis of
      carbasugars.
AB  - 4,5-Dimethylenecyclohex-1-ene was subjected to a photooxygenation reaction to
      introduce oxygen functionalities. The endoperoxide obtained underwent an ene
      reaction to form hydroperoxides with 1,3-diene structures. Further addition of
      singlet oxygen to the diene units resulted in the formation of tricyclic
      hydroperoxides having three oxygens in the molecule. Cleavage of the oxygen
      oxygen bonds followed by epoxidation of the remaining C-C double bond and
      concomitant ring-opening reaction furnished the isomeric carbasugars. 

PMID- 23962301
TI  - Hexagonal crown-capped zinc oxide micro rods: hydrothermal growth and formation
      mechanism.
AB  - Hexagonal crown-capped ZnO micro rods were successfully prepared by a facile low
      temperature hydrothermal method. The as-prepared ZnO micro rods are 4.4-5.2 MUm
      in length and 2.4-3.6 MUm in diameter, possessing a single-crystal hexagonal
      structure. The morphology evolution and structure changes were tracked during
      hydrothermal growth by field-emission scanning electron microscopy and X-ray
      diffraction, respectively. A three-stage growth mechanism of the hexagonal crown
      capped ZnO micro rods was proposed and further verified by a growth solution
      renewal experiment. The room-temperature photoluminescence (PL) spectrum of the
      hexagonal crowns exhibits a strong UV emission at about 382 nm. The temperature
      dependent PL results indicate that the UV emission originates from the radiative
      free-exciton recombination. 

PMID- 23962303
TI  - Thermoresponsive synthetic polymer-microtubule hybrids.
AB  - Thermoresponsive hybrids consisting of synthetic polymers and microtubules (MTs),
      i.e., assemblies of tubulins, were prepared by bonding MTs covalently to a few
      reactive units in a macromolecular strand. The hybrids exhibited the gel/sol
      transition because of the "assembling of tubulins to MTs/disintegrating of MTs to
      tubulins" by the temperature change between 37 and 4  degrees C, respectively.
      The viscoelastic behaviors of the hybrid gels depended upon the quantity of
      polymer feed and the amount of resulting covalent bonds between the polymers and
      tubulin units. Furthermore, in a confined space of a thin and long rectangular
      cell with the temperature gradient from 4  degrees C (cold terminal) to 37 
      degrees C (warm terminal), the sol state hybrid turned to the gel state that
      propagated from the warm terminal toward the cold terminal to form uniaxially
      oriented MT arrays. Upon changing the temperature of the whole system between 37
      and 4  degrees C, the uniaxial arrays appeared/disappeared reversibly. 

PMID- 23962302
TI  - Influenza virus A M2 protein generates negative Gaussian membrane curvature
      necessary for budding and scission.
AB  - The M2 protein is a multifunctional protein, which plays several roles in the
      replication cycle of the influenza A virus. Here we focus on its ability to
      promote budding of the mature virus from the cell surface. Using high-resolution
      small-angle X-ray scattering we show that M2 can restructure lipid membranes into
      bicontinuous cubic phases which are rich in negative Gaussian curvature (NGC).
      The active generation of negative Gaussian membrane curvature by M2 is essential
      to influenza virus budding. M2 has been observed to colocalize with the region of
      high NGC at the neck of a bud. The structural requirements for scission are even
      more stringent than those for budding, as the neck must be considerably smaller
      than the virus during 'pinch off'. Consistent with this, the amount of NGC in the
      induced cubic phases suggests that M2 proteins can generate high curvatures
      comparable to those on a neck with size 10* smaller than a spherical influenza
      virus. Similar experiments on variant proteins containing different M2 domains
      show that the cytoplasmic amphipathic helix is necessary and sufficient for NGC
      generation. Mutations to the helix which reduce its amphiphilicity and are known
      to diminish budding attenuated NGC generation. An M2 construct comprising the
      membrane interactive domains, the transmembrane helix and the cytoplasmic helix,
      displayed enhanced ability to generate NGC, suggesting that other domains
      cooperatively promote membrane curvature. These studies establish the importance
      of M2-induced NGC during budding and suggest that antagonizing this curvature is
      a viable anti-influenza strategy. 

PMID- 23962304
TI  - Physicians' perceptions of medical representative visits in Yemen: a qualitative
      study.
AB  - BACKGROUND: The pharmaceutical industry invests heavily in promotion, and it uses
      a variety of promotional strategies to influence physicians' prescribing
      decisions. Within this context, medical representatives (MRs) are the key
      personnel employed in promoting their products. One significant consequence of
      the interactions between physicians and medical representatives is a conflict of
      interests which may contribute to the over prescribing of medications and thus
      negative effects on patients' health and economics. There is limited detailed
      information published on the reasons why physicians interact with pharmaceutical
      representatives. This study aims to qualitatively explore physicians' attitudes
      about interactions with medical representatives and their reasons for accepting
      the medical representatives' visits. METHODS: In-depth interviews were used to
      gain a better understanding of physicians' perceptions of medical representative
      visits. A total of 32 physicians from both private and public hospitals were
      interviewed. The recordings of the interviews were transcribed verbatim and
      subject to thematic analysis using a framework analysis approach. RESULTS: The
      present qualitative study found that the majority of the physicians had positive
      interactions with medical representatives. The physicians' main reasons stated
      for allowing medical representatives' visits are the social contacts and mutual
      benefits they will gain from these representatives. They also emphasized that the
      meeting with representatives provides educational and scientific benefits. A few
      physicians stated that the main reasons behind refusing the meeting with medical
      representatives were lack of conviction about the product and obligation to
      prescribe medicine from the representative company. Most of the physicians
      believed that they were under marketing pressure to prescribe certain medicines.
      CONCLUSIONS: Although physicians are aware that the medical representatives could
      influence their prescribing decision, they welcome representatives to visit them
      and consider receiving free samples, gifts and various kinds of support as a
      normal practice. The findings provided insight into possible target areas for
      educational interventions concerning pharmaceutical marketing. Such a finding
      will provide the basis for policymakers in the public and private health sector
      in Yemen to develop a suitable policy and regulations in terms of drug promotion.

PMID- 23962305
TI  - Individualized fetal growth assessment: critical evaluation of key concepts in
      the specification of third trimester size trajectories.
AB  - OBJECTIVES: To characterize second and third trimester fetal growth using
      Individualized Growth Assessment methods in a larger cohort of fetuses with
      normal neonatal growth outcomes. METHODS: A prospective longitudinal study of 119
      pregnancies was performed from 18 weeks, MA, to delivery. Measurements of several
      1D and 3D fetal size parameters were obtained from 3D volume data sets at 3-4
      week intervals. Regression analyses were used to determine Start Points (SP) and
      Rossavik model (P = c {t} (k + st)) coefficients c. k and s for each parameter in
      each fetus. Second trimester growth velocity reference ranges were determined and
      size model specification functions re-established, the latter used to generate
      individual size models. Actual measurements were compared to predicted third
      trimester size trajectories using Percent Deviations. New age-specific reference
      ranges for the Percent Deviations of each parameter were defined using 2-level
      statistical modeling. RESULTS: Rossavik models fit the data for all parameters
      very well (R(2): 99%), with SP's and k values similar to those found in much
      smaller cohorts. The c* values were strongly related to the second trimester
      slope (R(2): 97%), as was predicted s* to estimated c* (R(2): 54--95%). Rossavik
      models predicted third trimester growth with systematic errors close to 0%;
      random errors (95% range) ranged between 5.7 and 10.9% and 20.0 and 24.3% for 1D
      and 3D parameters, respectively. CONCLUSIONS: IGA procedures for evaluating
      second and third trimester growth are now established based on a larger cohort (4
      6 fold larger). New, more rigorously defined, age-specific standards for the
      evaluation of third trimester size deviations are now available for nine
      anatomical parameters and a weight estimation procedure that incorporates a soft
      tissue parameter (fractional thigh volume). These results provide a means for
      more reliably assessing fetal growth on an individualized basis, thus minimizing
      the effect of biological differences in growth.

PMID- 23962306
TI  - Water clustering in glassy polymers.
AB  - In this study, water solubility and water clustering in several glassy polymers,
      including poly(methyl methacrylate) (PMMA), poly(styrene) (PS), and
      poly(vinylpyrrolidone) (PVP), were measured using both quartz spring microbalance
      (QSM) and Fourier transform infrared-attenuated total reflectance (FTIR-ATR)
      spectroscopy. Specifically, QSM was used to determine water solubility, while
      FTIR-ATR spectroscopy provided a direct, molecular-level measurement of water
      clustering. The Flory-Huggins theory was employed to obtain a measure of water
      polymer interaction and water solubility, through both prediction and regression,
      where the theory failed to predict water solubility in both PMMA and PVP.
      Furthermore, a comparison of water clustering between direct FTIR-ATR
      spectroscopy measurements and predictions from the Zimm-Lundberg clustering
      analysis produced contradictory results. The failure of the Flory-Huggins theory
      and Zimm-Lundberg clustering analysis to describe water solubility and water
      clustering, respectively, in these glassy polymers is in part due to the
      equilibrium constraints under which these models are derived in contrast to the
      nonequilibrium state of glassy polymers. Additionally, FTIR-ATR spectroscopy
      results were compared to temperature-dependent diffusivity data, where a
      correlation between the activation energy for diffusion and the measured water
      clustering was observed. 

PMID- 23962307
TI  - Nitric oxide-releasing amphiphilic poly(amidoamine) (PAMAM) dendrimers as
      antibacterial agents.
AB  - A series of amphiphilic nitric oxide (NO)-releasing poly(amidoamine) (PAMAM)
      dendrimers with different exterior functionalities were synthesized by a ring
      opening reaction between primary amines on the dendrimer and propylene oxide
      (PO), 1,2-epoxy-9-decene (ED), or a ratio of the two, followed by reaction with
      NO at 10 atm to produce N-diazeniumdiolate-modified scaffolds with a total
      storage of ~1 MUmol/mg. The hydrophobicity of the exterior functionality was
      tuned by varying the ratio of PO and ED grafted onto the dendrimers. The
      bactericidal efficacy of these NO-releasing vehicles against established Gram
      negative Pseudomonas aeruginosa biofilms was then evaluated as a function of
      dendrimer exterior hydrophobicity (i.e., ratio of PO/ED), size (i.e.,
      generation), and NO release. Both the size and exterior functionalization of
      dendrimer proved important to a number of parameters including dendrimer-bacteria
      association, NO delivery efficiency, bacteria membrane disruption, migration
      within the biofilm, and toxicity to mammalian cells. Although enhanced
      bactericidal efficacy was observed for the hydrophobic chains (e.g., ED),
      toxicity to L929 mouse fibroblast cells was also noted at concentrations
      necessary to reduce bacterial viability by 5-logs (99.999% killing). The optimal
      PO to ED ratios for biofilm eradication with minimal toxicity against L929 mouse
      fibroblast cells were 7:3 and 5:5. The study presented herein demonstrated the
      importance of both dendrimer size and exterior properties in determining efficacy
      against established biofilms without compromising biocompatibility to mammalian
      cells.

PMID- 23962308
TI  - Long-term successful healing of ulcerated necrobiosis lipoidica after topical
      therapy with becaplermin.
AB  - We report a case of chronic leg ulceration occurring in a patient with
      necrobiosis lipoidica (NL). After many topical treatments had failed to achieve
      healing, treatment with topical becaplermin was started, which resulted in rapid
      improvement and ultimately complete healing of the ulceration. Treatment of
      ulcerated NL is often disappointing. Many topical and systemic drugs have been
      tried. Becaplermin is a platelet-derived growth factor indicated for the
      treatment of neuropathic diabetic ulcers measuring < 50 mm in size. To our
      knowledge, this is only the second case reported in the literature of ulcerated
      NL successfully treated with becaplermin.

PMID- 23962309
TI  - A cohort study evaluation of maternal PCB exposure related to time to pregnancy
      in daughters.
AB  - BACKGROUND: Polychlorinated biphenyls (PCBs) remain ubiquitous environmental
      contaminants. Developmental exposures are suspected to impact reproduction.
      Analysis of mixtures of PCBs may be problematic as components have a complex
      correlation structure, and along with limited sample sizes, standard regression
      strategies are problematic. We compared the results of a novel, empirical method
      to those based on categorization of PCB compounds by (1) hypothesized biological
      activity previously proposed and widely applied, and (2) degree of ortho-
      substitution (mono, di, tri), in a study of the relation of maternal serum PCBs
      and daughter's time to pregnancy. METHODS: We measured PCBs in maternal serum
      samples collected in the early postpartum in 289 daughters in the Child Health
      and Development Studies birth cohort. We queried time to pregnancy in these
      daughters 28-31 years later. We applied a novel weighted quantile sum approach to
      find the bad-actor compounds in the PCB mixture found in maternal serum. The
      approach includes empirical estimation of the weights through a bootstrap step
      which accounts for the variation in the estimated weights. RESULTS: Bootstrap
      analyses indicated the dominant functionality groups associated with longer TTP
      were the dioxin-like, anti-estrogenic group (average weight, 22%) and PCBs not
      previously classified by biological activity (54%). In contrast, the unclassified
      PCBs were not important in the association with shorter TTP, where the anti
      estrogenic groups and the PB-inducers group played a more important role (60% and
      23%, respectively). The highly chlorinated PCBs (average weight, 89%) were mostly
      associated with longer TTP; in contrast, the degree of chlorination was less
      discriminating for shorter TTP. Finally, PCB 56 was associated with the strongest
      relationship with TTP with a weight of 47%. CONCLUSIONS: Our empirical approach
      found some associations previously identified by two classification schemes, but
      also identified other bad actors. This empirical method can generate hypotheses
      about mixture effects and mechanisms and overcomes some of the limitations of
      standard regression techniques.

PMID- 23962310
TI  - Discovery techniques for calcitonin gene-related peptide receptor antagonists for
      potential antimigraine therapies.
AB  - INTRODUCTION: Calcitonin gene-related peptide (CGRP) exerts a key function in
      migraine pathophysiology through the trigeminovascular system. Influencing this
      system via CGRP receptor antagonists seems to be an important new option in
      treating migraine attacks. To characterize new compounds, models are used to
      study the vascular effects as well as their effects on the central nervous
      system. AREAS COVERED: The authors review the clinical trials and many different
      in vitro and in vivo experimental models that have been used to investigate the
      effects and side effects in animals, healthy subjects and patients. These
      experimental models are essential, not only in characterizing new CGRP receptor
      antagonists, but also in gaining more insight into the pathophysiological
      mechanisms behind migraines. EXPERT OPINION: Although triptans were a major
      breakthrough in migraine treatment, they are not effective for every patient and
      contraindicated in patients with cardiovascular disease. There is still a demand
      for other acute antimigraine acting drugs with CGRP receptor antagonists being
      the most promising candidates. CGRP plays a role in protection against ischemia,
      but CGRP receptor antagonists do not seem to affect this protection to a harmfull
      extent, when used incidentally as acute antimigraine treatment. In order for drug
      specificity to be increased, the site of action needs to be identified; this
      consequently may lead to a decrease in dosing with fewer side effects.

PMID- 23962311
TI  - Towards non-invasive monitoring of pathogen-host interactions during Candida
      albicans biofilm formation using in vivo bioluminescence.
AB  - Candida albicans is a major human fungal pathogen causing mucosal and deep tissue
      infections of which the majority is associated with biofilm formation on medical
      implants. Biofilms have a huge impact on public health, as fungal biofilms are
      highly resistant against most antimycotics. Animal models of biofilm formation
      are indispensable for improving our understanding of biofilm development inside
      the host, their antifungal resistance and their interaction with the host immune
      defence system. In currently used models, evaluation of biofilm development or
      the efficacy of antifungal treatment is limited to ex vivo analyses, requiring
      host sacrifice, which excludes longitudinal monitoring of dynamic processes
      during biofilm formation in the live host. In this study, we have demonstrated
      for the first time that non-invasive, dynamic imaging and quantification of in
      vitro and in vivo C. albicans biofilm formation including morphogenesis from the
      yeast to hyphae state is feasible by using growth-phase dependent bioluminescent
      C. albicans strains in a subcutaneous catheter model in rodents. We have shown
      the defect in biofilm formation of a bioluminescent bcr1 mutant strain. This
      approach has immediate applications for the screening and validation
      ofantimycotics under in vivo conditions, for studying host-biofilm interactions
      in different transgenic mouse models and for testing the virulence of luminescent
      C. albicans mutants, hereby contributing to a better understanding of the
      pathogenesis of biofilm-associated yeast infections. 

PMID- 23962313
TI  - Does coping mediate the relationship between familism and caregiver outcomes?
AB  - OBJECTIVES: The sociocultural model of stress and coping, which despite receiving
      support from several studies conducted with diverse ethnic groups, has yet to be
      tested longitudinally or used within the context of positive caregiver outcomes.
      The aim of the current study was to test a specific component of the model, which
      posits that caregiver coping will be influenced by the cultural value of familism
      (feelings of solidarity and loyalty among family members), which will in turn
      affect caregiver outcomes. METHOD: A questionnaire was completed by 123 family
      caregivers in the UK assessing familism, use of coping strategies, caregiver
      gains, anxiety and depression at three time points over nine months. RESULTS:
      Mediation analysis followed guidelines proposed by Baron and Kenny. Religious
      coping and positive reframing at time 2 (T2) were found to significantly mediate
      between familism values at time 1 (T1) and caregiver gains at time 3 (T3).
      Behavioural disengagement at T2 was found to mediate between familism at T1 and
      caregiver depression at T3. Additionally familism was found to be positively
      associated with both negative and positive aspects of caregiving. CONCLUSION: Our
      longitudinal findings suggest that interventions and services acknowledging
      caregiver values and the associated coping responses may prove beneficial.

PMID- 23962312
TI  - Complete mitogenome sequences of four flatfishes (Pleuronectiformes) reveal a
      novel gene arrangement of L-strand coding genes.
AB  - BACKGROUND: Few mitochondrial gene rearrangements are found in vertebrates and
      large-scale changes in these genomes occur even less frequently. It is difficult,
      therefore, to propose a mechanism to account for observed changes in mitogenome
      structure. Mitochondrial gene rearrangements are usually explained by the
      recombination model or tandem duplication and random loss model. RESULTS: In this
      study, the complete mitochondrial genomes of four flatfishes, Crossorhombus
      azureus (blue flounder), Grammatobothus krempfi, Pleuronichthys cornutus, and
      Platichthys stellatus were determined. A striking finding is that eight genes in
      the C. azureus mitogenome are located in a novel position, differing from that of
      available vertebrate mitogenomes. Specifically, the ND6 and seven tRNA genes (the
      Q, A, C, Y, S1, E, P genes) encoded by the L-strand have been translocated to a
      position between tRNA-T and tRNA-F though the original order of the genes is
      maintained. CONCLUSIONS: These special features are used to suggest a mechanism
      for C. azureus mitogenome rearrangement. First, a dimeric molecule was formed by
      two monomers linked head-to-tail, then one of the two sets of promoters lost
      function and the genes controlled by the disabled promoters became pseudogenes,
      non-coding sequences, and even were lost from the genome. This study provides a
      new gene-rearrangement model that accounts for the events of gene-rearrangement
      in a vertebrate mitogenome.

PMID- 23962314
TI  - Patterns of human interlimb coordination emerge from the properties of non
      linear, limit cycle oscillatory processes.
AB  - The present article represents an initial attempt to offer a principled solution
      to a fundamental problem of movement identified by Bernstein (1967), namely, how
      the degrees of freedom of the motor system are regulated. Conventional views of
      movement control focus on motor programs or closed-loop devices and have little
      or nothing to say on this matter. As an appropriate conceptual framework we offer
      Iberall and his colleagues' physical theory of homeokinetics first elaborated for
      movement by Kugler, Kelso, and Turvey (1980). Homeokinetic theory characterizes
      biological systems as ensembles of non-linear, limit cycle oscillatory processes
      coupled and mutually entrained at all levels of organization. Patterns of
      interlimb coordination may be predicted from the properties of non-linear, limit
      cycle oscillators. In a set of experiments and formal demonstrations we show that
      cyclical, two-handed movements maintain fixed amplitude and frequency (a stable
      limit cycle organization) under the following conditions: (a) when brief and
      constantly applied load perturbations are imposed on one hand or the other, (b)
      regardless of the presence or absence of fixed mechanical constraints, and (c) in
      the face of a range of external driving frequencies from a visual source. In
      addition, we observe a tight phasic relationship between the hands before and
      after perturbations (quantified by cross-correlation techniques), a tendency of
      one limb to entrain the other (mutual entrainment) and that limbs cycling at
      different frequencies reveal non-arbitrary, sub-harmonic relationships (small
      integer, subharmonic entrainment). In short, all the above patterns of interlimb
      coordination fall out of a non-linear oscillatory design. Discussion focuses on
      the compatibility of these results with past and present neurobiological work,
      and the theoretical insights into problems of movement offered by homeokinetic
      physics. Among these are, we think, the beginnings of a principled solution to
      the degrees of freedom problem, and the tentative claim that coordination and
      control are emergent consequences of dynamical interactions among non-linear,
      limit cycle oscillatory processes. 

PMID- 23962315
TI  - First isolation of hirame rhabdovirus from freshwater fish in Europe.
AB  - A rhabdovirus was isolated in cell culture inoculated with tissue material from
      diseased grayling, Thymallus thymallus (L.), originating from a fish farm
      affected by a mortality episode in Poland. Diagnostics tests showed that the
      virus was not related to novirhabdoviruses known in Europe, nor to vesiculovirus
      like species, except perch rhabdovirus (PRhV) with which it shared moderate
      serological relations. However, RT-PCR with PRhV probes gave negative results. To
      identify the virus, a random-priming sequence-independent single primer
      amplification was adopted. Surprisingly, two of the obtained sequences exhibited
      a high identity (>99%) with hirame rhabdovirus (HIRRV), a novirhabdovirus usually
      found in fish in marine Asiatic countries, for instance Japan, China and Korea.
      The full-length sequence of the phosphoprotein gene (P) demonstrated a higher
      identity of the present isolate with HIRRV from China compared with the Korean
      isolate. An identical viral sequence was also found in brown trout, Salmo trutta
      trutta L., affected by mortalities in a second farm in the same region, after a
      likely contamination from the grayling farm. To our knowledge, this is the first
      report of HIRRV in Europe, and in two hosts from fresh water that have not been
      described before as susceptible species. 

PMID- 23962316
TI  - Preferring familiar emotions: as you want (and like) it?
AB  - Do people want to feel emotions that are familiar to them? In two studies,
      participants rated how much they typically felt various emotions (i.e.,
      familiarity of the emotion) and how much they generally wanted to experience
      these emotions. We found that, in general, people wanted to feel pleasant
      emotions more than unpleasant emotions. However, for both pleasant and unpleasant
      emotions, people more (vs. less) familiar with an emotion also wanted to
      experience it more. Links between the familiarity of an emotion and wanting to
      experience that emotion were not explained by the concurrent experience of
      familiar emotions. Also, we show that although familiar emotions were also liked
      more, liking did not fully account for wanting familiar emotions. Finally, the
      familiarity of emotions mediated the links between trait affect and the emotions
      people wanted to feel. We propose that people are motivated to feel familiar
      emotions, in part, because of their instrumental value. 

PMID- 23962318
TI  - The Nordic maintenance care program: what is maintenance care? Interview based
      survey of Danish chiropractors.
AB  - OBJECTIVE: To describe and interpret Danish Chiropractors' perspectives regarding
      the purpose and rationale for using MC (maintenance care), its content, course
      and patient characteristics. METHODS: Semi-structured interviews were conducted
      with 10 chiropractors identified using a stratified, theoretical sampling
      framework. Interviews covered four domains relating to MC, namely: purpose,
      patient characteristics, content, and course and development. Data was analysed
      thematically. RESULTS: Practitioners regard MC primarily as a means of providing
      secondary or tertiary care and they primarily recommend it to patients with a
      history of recurrence. Initiating MC is often a shared decision between clinician
      and patient. The core elements of MC are examination and manipulation, but
      exercise and general lifestyle advice are often included. Typically, treatment
      intervals lie between 2 and 4 months. Clinician MC practices seem to evolve over
      time and are informed by individual practice experiences.Chiropractors are more
      likely to offer MC to patients whose complaints include a significant muscular
      component. Furthermore, a successful transition to MC appears dependent on
      correctly matching complaint with management. A positive relationship between
      chiropractor and patient facilitates the initiation of MC. Finally; MC appears
      grounded in a patient-oriented approach to care rather than a market-oriented
      one. CONCLUSION: MC is perceived as both a secondary and tertiary preventative
      measure and its practice appears grounded in the tenet of patient-oriented care.
      A positive personal relationship between chiropractor and patient facilitates the
      initiation of MC. The results from this and previous studies should be considered
      in the design of studies of efficacy.

PMID- 23962317
TI  - The N-terminal region of the Neurospora NDR kinase COT1 regulates morphology via
      its interactions with MOB2A/B.
AB  - Nuclear Dbf2p-related (NDR) protein kinases are important for cell
      differentiation and polar morphogenesis in various organisms, yet some of their
      functions are still elusive. Dysfunction of the Neurospora crassa NDR kinase COT1
      leads to cessation of tip extension and hyperbranching. NDR kinases require the
      physical interaction between the kinase's N-terminal region (NTR) and the MPS1
      binding (MOB) proteins for their activity and functions. To study the
      interactions between COT1 and MOB2 proteins, we mutated several conserved
      residues and a novel phosphorylation site within the COT1 NTR. The phenotypes of
      these mutants suggest that the NTR is required for COT1 functions in regulating
      hyphal elongation and branching, asexual conidiation and germination.
      Interestingly, while both MOB2A and MOB2B promote proper hyphal growth, they have
      distinct COT1-dependent roles in regulation of macroconidiation.
      Immunoprecipitation experiments indicate physical association of COT1 with both
      MOB2A and MOB2B, simultaneously. Furthermore, the binding of the two MOB2
      proteins to COT1 is mediated by different residues at the COT1 NTR, suggesting a
      hetero-trimer is formed. Thus, although MOB2A/B may have some overlapping
      functions in regulating hyphal tip extension, their function is not redundant and
      they are both required for proper fungal development. 

PMID- 23962319
TI  - The good, the bad and the early adopters: providers' attitudes about a common,
      commercial EHR.
AB  - RATIONALE, AIMS AND OBJECTIVES: To describe primary care providers' (PCP)
      attitudes about the impact of a mature, commercial electronic health records
      (EHR) on clinical practice in settings with experience using the system and to
      evaluate whether a provider's propensity to adopt new technologies is associated
      with more favourable perceptions. METHOD: We surveyed PCPs in 11 practices
      affiliated with three health systems in Texas. Most practices had greater than 5
      years of experience with the Epic EHR. The effect of early adopter of technology
      status was evaluated using logistic regression. RESULTS: One hundred forty-six
      PCPs responded (70%). Most thought the EHR had a positive impact on routine
      tasks, such as prescription refills (94%), whereas fewer agreed for complex
      tasks, such as delivery of guideline-concordant care for chronic illnesses (51%).
      Two-thirds (62%) thought it interfered with eye contact with patients, and 40%
      reported that it interfered with in-visit communication. Early adopters of
      technology reported greater positive effects of the EHR, even after adjusting for
      age, ranging from 2% to 15% higher on satisfaction ratings. CONCLUSION: PCPs
      practicing in settings with considerable experience using a common commercial EHR
      identified many positive effects, as well as two key areas for improvement -
      patient centredness and intelligent decision support. Providers with a propensity
      to adopt new technologies have more favourable perceptions of the EHR.

PMID- 23962320
TI  - Two new flavonol glycosides and biological activities of Diplotaxis harra
      (Forssk.) Boiss.
AB  - Two new flavonol glycosides, isorhamnetin 3-O-beta-glucopyranoside-4'-O-beta
      xylopyranoside (1) and kaempferol 3-O-beta-glucopyranoside -4'-O-beta
      xylopyranoside (2), were isolated from the defatted aqueous methanol extract of
      the whole plant Diplotaxis harra along with 12 known flavonols (3-14). They were
      characterised by chemical and spectral methods. The 70% aqueous methanol,
      chloroform and defatted aqueous methanol plant extracts exhibited significant
      antioxidant effects (nitroblue tetrazolium reduction method). Their cytotoxic
      activity was carried out against 11 tumour cell lines (sulphorhodamine B assay).
      The three extracts expressed the greatest antiproliferative activity against
      colon 38, P388 and MKN-28 with GI50 (0.45, 0.4, 0.07 MUg/mL) and against P388 [3
      (4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay] with IC50 (0.26,
      0.24, 0.25 MUg/mL), respectively. The chloroform extract showed the highest
      activity as eukaryotic DNA topoisomerase II inhibitors of P388 with IC50 0.24
      MUg/mL. Antiviral screening of the extracts and the pure compounds against foot
      and-mouth disease virus types A and O revealed a prominent inhibition of its
      cytopathic effect.

PMID- 23962322
TI  - Exploring the prevalence and phenomenology of repetitive behaviours and abnormal
      sensory processing in children with Williams Syndrome.
AB  - BACKGROUND: A small amount of research with individuals who have Williams
      Syndrome (WS) suggests that children with the condition may be vulnerable to
      sensory processing abnormalities and present with repetitive and restricted
      behaviours. METHODS: Parents of 21 children with WS aged 6-15 years completed a
      semi-structured interview designed to elicit the form, frequency, impact and
      developmental course of a range of sensory processing abnormalities and
      repetitive behaviours. RESULTS: Findings indicate that sensory processing
      difficulties are predominantly characterised by hypersensitivities, particularly
      in relation to vestibular, auditory, gustatory and proprioceptive functioning.
      Parents also reported the presence of a range of restricted and repetitive
      behaviours, which were often associated with their child's sensory symptoms.
      CONCLUSIONS: This study makes a significant contribution to our understanding of
      sensory functioning and repetitive behaviours in WS. It also highlights the need
      for a multidisciplinary assessment of the difficulties experienced by children
      with the disorder.

PMID- 23962321
TI  - Primed low-frequency repetitive transcranial magnetic stimulation and constraint
      induced movement therapy in pediatric hemiparesis: a randomized controlled trial.
AB  - AIM: The aim of this study was to determine the feasibility and efficacy of five
      treatments of 6 Hz primed, low-frequency, repetitive transcranial magnetic
      stimulation (rTMS) combined with constraint-induced movement therapy (CIMT) to
      promote recovery of the paretic hand in children with congenital hemiparesis.
      METHOD: Nineteen children with congenital hemiparesis aged between 8 and 17 years
      (10 males, nine females; mean age 10 years 10 months, SD 2 years 10 months;
      Manual Ability Classification Scale levels I-III) underwent five sessions of
      either real rTMS (n=10) or sham rTMS (n=9) alternated daily with CIMT. CIMT
      consisted of 13 days of continuous long-arm casting with five skin-check
      sessions. Each child received a total of 10 hours of one-to-one therapy. The
      primary outcome measure was the Assisting Hand Assessment (AHA) and the secondary
      outcome variables were the Canadian Occupational Performance Measure (COPM) and
      stereognosis. A Wilcoxon signed-rank sum test was used to analyze differences
      between pre- and post-test scores within the groups. Analysis of covariance was
      used to compute mean differences between groups adjusting for baseline. Fisher's
      exact test was used to compare individual change in AHA raw scores with the
      smallest detectable difference (SDD) of 4 points. RESULTS: All participants
      receiving treatment finished the study. Improvement in AHA differed significantly
      between groups (p=0.007). No significant differences in the secondary outcome
      measures were found. Eight out of 10 participants in the rTMS/CIMT group showed
      improvement greater than the SDD, but only two out of nine in the sham rTMS/CIMT
      group showed such improvement (p=0.023). No serious adverse events occurred.
      INTERPRETATION: Primed, low-frequency rTMS combined with CIMT appears to be safe,
      feasible, and efficacious in pediatric hemiparesis. Larger clinical trials are
      now indicated.

PMID- 23962323
TI  - Intramolecular vinyl quinone Diels-Alder reactions: asymmetric entry to the
      cordiachrome core and synthesis of (-)-isoglaziovianol.
AB  - A short and asymmetric entry to the core structure of the cordiachromes has been
      developed, allowing access to (-)-isoglaziovianol in seven steps. Our synthesis
      includes a Trost asymmetric allylic alkylation and a reaction cascade triggered
      by a vinyl quinone Diels-Alder reaction and followed by intramolecular
      nucleophilic interception. 

PMID- 23962325
TI  - An ethnomethodological approach to examine exploitation in the context of
      capacity, trust and experience of commercial surrogacy in India.
AB  - The socio-ethical concerns regarding exploitation in commercial surrogacy are
      premised on asymmetric vulnerability and the commercialization of women's
      reproductive capacity to suit individualistic motives. In examining the
      exploitation argument, this article reviews the social contract theory that
      describes an individual as an 'economic man' with moral and/or political
      motivations to satisfy individual desires. This study considers the critique by
      feminists, who argue that patriarchal and medical control prevails in the
      surrogacy contracts. It also explores the exploitative dynamics amongst actors in
      the light of Baier's conceptualization of trust and human relationship, within
      which both justice and exploitation thrive, and Foucault's concept of bio-power.
      Drawing on these concepts, this paper aims to investigate the manifestations of
      exploitation in commercial surrogacy in the context of trust, power and
      experiences of actors, using a case study of one clinic in India. The actors'
      experiences are evaluated at different stages of the surrogacy process:
      recruitment, medical procedures, living in the surrogate home, bonding with the
      child and amongst actors, financial dealings, relinquishment and post
      relinquishment.This study applies ethnomethodology to identify phenomena as
      perceived by the actors in a situation, giving importance to their
      interpretations of the rules that make collective activity possible. The methods
      include semi-structured interviews, discussions, participant observation and
      explanation of the phenomena from the actors' perspectives. Between August 2009
      and April 2010, 13 surrogate mothers (SMs), 4 intended parents (IPs) and 2
      medical practitioners (MPs) from one clinic in Western India were
      interviewed.This study reveals that asymmetries of capacity amongst the MPs, SMs,
      IPs and surrogate agents (SAs) lead to a network of trust and designation of
      powers through rules, bringing out the relevance of Baier's conceptualization of
      asymmetric vulnerability, trust and potential exploitation in human
      relationships. The IPs are exploited, especially in monetary terms. The SMs are
      relatively the most exploited, given their vulnerability. Their remuneration
      through surrogacy is significant for them, and their acquired knowledge as ex
      surrogates is used for their own benefit and for exploiting others. Foucault's
      conceptualization of power is hence relevant, since the ex-SMs re-invest the
      power of their exploitative experience in exploiting others. 

PMID- 23962324
TI  - Molecular dynamics perspective on the protein thermal stability: a case study
      using SAICAR synthetase.
AB  - The enzyme SAICAR synthetase ligates aspartate with CAIR (5'-phosphoribosyl-4
      carboxy-5-aminoimidazole) forming SAICAR (5-amino-4-imidazole-N
      succinocarboxamide ribonucleotide) in the presence of ATP. In continuation with
      our previous study on the thermostability of this enzyme in hyper-/thermophiles
      based on the structural aspects, here, we present the dynamic aspects that
      differentiate the mesophilic (E. coli, E. chaffeensis), thermophilic (G.
      kaustophilus), and hyperthermophilic (M. jannaschii, P. horikoshii) SAICAR
      synthetases by carrying out a total of 11 simulations. The five functional dimers
      from the above organisms were simulated using molecular dynamics for a period of
      50 ns each at 300 K, 363 K, and an additional simulation at 333 K for the
      thermophilic protein. The basic features like root-mean-square deviations, root
      mean-square fluctuations, surface accessibility, and radius of gyration revealed
      the instability of mesophiles at 363 K. Mean square displacements establish the
      reduced flexibility of hyper-/thermophiles at all temperatures. At the
      simulations time scale considered here, the long-distance networks are
      considerably affected in mesophilic structures at 363 K. In mesophiles, a
      comparatively higher number of short-lived (having less percent existence time)
      Calpha, hydrogen bonds, hydrophobic interactions are formed, and long-lived (with
      higher percentage existence time) contacts are lost. The number of time-averaged
      salt-bridges is at least 2-fold higher in hyperthermophiles at 363 K. The change
      in surface accessibility of salt-bridges at 363 K from 300 K is nearly doubled in
      mesophilic protein compared to proteins from other temperature classes. 

PMID- 23962326
TI  - Object-centered neglect in patients with unilateral neglect: effects of left
      right coordinates of objects.
AB  - Abstract When patients with right-sided hemispheric lesions neglect information
      on the left side, with respect to what set of spatial coordinates is left
      defined? Two potential reference frames were examined in this study, one where
      left and right are defined with respect to the midline of the viewer and/or
      environment (viewer/env-centered) and the other where left and right are defined
      with respect to the midline of the object (object-centered). By rotating the
      stimulus 90 degrees  clockwise or counterclockwise, and instructing patients with
      neglect to report the colors appearing around the border of a stimulus, an
      independent measure was obtained for the number of colors reported from the left
      and right of the viewer/env- and from the object-based reference frame. Whereas
      significant object-centered neglect was observed only for upper case asymmetrical
      letters but not for symmetrical letters nor for drawings of familiar animals or
      objects, significant viewer/env-based neglect was observed with all the stimulus
      types. We present an account of the coexistence of neglect in more than one frame
      of reference and the presence of object-centered neglect under a restricted set
      of conditions. 

PMID- 23962327
TI  - The Role of the Anterior Attention System in Semantic Processing of both Foveal
      and Parafoveal Words.
AB  - Abstract This research takes advantage of combined cognitive and anatomical
      studies to ask whether attention is necessary for high-level word processing to
      occur. In Experiment 1 we used a lexical decision task in which two prime words,
      one in the fovea and the other in the parafovea, appeared simultaneously for 150
      msec, followed by a foveal target (word/nonword). Target words were semantically
      related either to the foveal or to the parafoveal word, or unrelated to them. In
      one block of trials subjects were also required to perform an auditory shadowing
      task. From PET studies we know that shadowing activates the anterior cingulate
      cortex, involved in selective attention. If the anterior attention system is
      always involved in semantic processing, shadowing should reduce semantic priming
      obtained from both foveal and parafoveal words. In contrast, if semantic priming
      by parafoveal words is independent of activation in that attention area, priming
      will not be affected by shadowing. Our results supported the latter hypothesis. A
      large priming effect arose from foveal primes, which was reduced by shadowing.
      For parafoveal primes a smaller priming effect arose, which was not affected by
      shadowing. In Experiment 2 prime words were masked. Semantic priming was reliable
      for both foveal and parafoveal words but there were then no differences between
      them. Most important, the size of priming was similar to that obtained from
      parafoveal words in Experiment 1. We conclude that the anterior attention system
      increases the potency of processing of consciously perceived stimuli, but there
      is a component of semantic priming that occurs without both focusing of attention
      and awareness, involving different cerebral areas to those involved in attention
      to language. 

PMID- 23962328
TI  - Summation priming and coarse semantic coding in the right hemisphere.
AB  - Abstract There are now numerous observations of subtle right hemisphere (RH)
      contributions to language comprehension. It has been suggested that these
      contributions reflect coarse semantic coding in the RH. That is, the RH weakly
      activates large semantic fields-including concepts distantly related to the input
      word-whereas the left hemisphere (LH) strongly activates small semantic fields
      limited to concepts closely related to the input (Beeman, 1993a,b). This makes
      the RH less effective at interpreting single words, but more sensitive to
      semantic overlap of multiple words. To test this theory, subjects read target
      words preceded by either "Summation" primes (three words each weakly related to
      the target) or Unrelated primes (three unrelated words), and target exposure
      duration was manipulated so that subjects correctly named about half the target
      words in each hemifield. In Experiment 1, subjects benefited more from Summation
      primes when naming target words presented to the left visual field-RH (Ivf-RH)
      than when naming target words presented to the right visual field-LH (rvf-LH),
      suggesting a RH advantage in coarse semantic coding. In Experiment 2, with a low
      proportion of related prime-target trials, subjects benefited more from "Direct"
      primes (one strong associate flanked by two unrelated words) than from Summation
      primes for rvf-LH target words, indicating that the LH activates closely related
      information much more strongly than distantly related information. Subjects
      benefited equally from both prime types for Ivf-RH target words, indicating that
      the RH activates closely related information only slightly more strongly, at
      best, than distantly related information. This suggests that the RH processes
      words with relatively coarser coding than the LH, a conclusion consistent with a
      recent suggestion that the RH coarsely codes visual input (Kosslyn, Chabris, Mar
      solek, & Koenig, 1992). 

PMID- 23962329
TI  - The nature and limits of orientation and pattern processing supporting visuomotor
      control in a visual form agnosic.
AB  - Abstract We have previously reported that a patient (DF) with visual form agnosia
      shows accurate guidance of hand and finger movements with respect to the size,
      orientation, and shape of the objects to which her movements are directed.
      Despite this, she is unable to indicate any knowledge about these object
      properties. In the present study, we investigated the extent to which DF is able
      to use visual shape or pattern to guide her hand movements. In the first
      experiment, we found that when presented with a stimulus aperture cut in the
      shape of the letter T, DF was able to guide a T-shaped form into it on about half
      of the trials, across a range of different stimulus orientations. On the
      remaining trials, her responses were almost always perpendicular to the correct
      Orientation. Thus, the visual information guiding the rotation of DF's hand
      appears to be limited to a single orientation. In other words, the visuomotor
      transformations mediating her hand rotation appear to be unable to combine the
      orientations of the stem and the top of the T, although they are sensitive to the
      orientation of the element(s) that comprise the T. In a second experiment, we
      examined her ability to use different sources of visual information to guide her
      hand rotation. In this experiment, DF was required to guide the leading edge of a
      hand-held card onto a rectangular target positioned at dHerent orientations on a
      flat surface. Here the orientation of her hand was determined primarily by the
      predominant orientation of the luminance edge elements present in the stimulus,
      rather than by information about orientation that was conveyed by nonluminance
      boundaries. Little evidence was found for an ability to use contour boundaries
      defined by Gestalt principles of grouping (good continuation or similarity) or
      "nonaccidental" image properties (colinearity) to guide her movements. We have
      argued elsewhere that the dorsal visual pathway from occipital to parietal cortex
      may underlie these preserved visuomotor skills in DF. If so, the limitations in
      her ability to use different kinds of "pattern" information to guide her hand
      rotation suggest that such information may need to be transmitted from the
      ventral visual stream to these parietal areas to enable the full range of
      prehensive acts in the intact individual. 

PMID- 23962330
TI  - The impact of semantic memory loss on phonological representations.
AB  - Abstract Three patients with semantic dementia, involving progressive
      deterioration of semantic memory, performed immediate serial recall of short
      sequences of familiar words. On the basis of their performance in other tasks of
      word comprehension and production, the stimuli were selected individually for
      each patient as either known or unknown words. All patients showed a marked
      advantage in recall of known as compared to familiar but now unknown words.
      Errors consisted primarily of incorrect combinations of correct phoneme sequences
      in the stimulus string, with a large number of errors preserving onsethime
      syllable structure (e.g., mint, rug reproduced as "rint, mug"). Discussion
      focuses on the implication of these errors for the structure of phonological
      representations, and in particular on a hypothesis that meaning plays a crucial
      role in binding the elements of phonological word forms. 

PMID- 23962331
TI  - Global semantic expectancy and language comprehension.
AB  - Abstract Previous research on the N400 component of the event-related brain
      potential (ERP) has dealt primarily with measuring the degree of expectancy on
      the part of the reader as a result of the context within a sentence. Research has
      shown that when the final word in a sentence is unexpected or incoherent, a
      greater N400 amplitude is elicited than if the final word is expected or coherent
      within the context of the sentence. The present study investigated whether the
      N400 component is sensitive to global, as well as local, semantic expectancy.
      Global coherence refers to the ease with which subjects can relate the current
      proposition they are reading with theme-related ideas. In the present study, the
      effect of global coherence on event-related brain potentials was tested using
      four titled and untitled paragraphs (Bransford & Johnson, 1972; Dooling &
      Lachman, 1971), presented one word at a time. These paragraphs are noncoherent,
      and are made coherent only with the presentation of a title. The EEG was recorded
      in response to every word in all four paragraphs. We found an increase in N400
      amplitude in response to the words in the Untitled paragraphs relative to the
      Titled paragraphs, indicating that global coherence does affect the N400. In
      addition, subjects in the Titled group showed an enhanced P1-N1 component
      relative to the Untitled group suggesting that the presence of global coherence
      allows greater attention to be allocated to early visual processing of words. 

PMID- 23962332
TI  - Independent attentional scanning in the separated hemispheres of split-brain
      patients.
AB  - Abstract Previous studies of visuospatial attention indicated that the isolated
      cerebral hemispheres of split-brain patients maintain an integrated, unitary
      focus of attention, presumably due to subcortical attentional mechanisms. The
      present study examined whether a unitary attentional focus would also be observed
      during a visual search task in which subjects scanned stimulus arrays for a
      target item. In a group of four commis-surotomy patients, the search rate for
      bilateral stimulus arrays was found to be approximately twice as fast as the
      search rate for unilateral arrays, indicating that the separated hemispheres were
      able to scan their respective hemifields independently. In contrast, the search
      rates for unilateral and bilateral arrays were approximately equal in a group of
      six normal control subjects, suggesting that the intact corpus callosum in these
      subjects is responsible for maintaining a unitary attentional focus during visual
      search. 

PMID- 23962333
TI  - On language.
AB  - Abstract Steven Pinker is a professor in the Department of Brain and Cognitive
      Sciences at MIT, and in 1994 will become director of its McDonnell-Pew Center for
      Cognitive Neuroscience. He received his B.K from McGill University in 1976 and
      his Ph.D. from Harvard University in 1979, both in experimental psychology, and
      taught at Harvard and Stanford before joining the faculty of MIT in 1982. He has
      done research in visual cognition and the psychology of language, and is the
      author of Language Learnability and Language Development (1984) and Learnability
      and Cognition (1989) and the editor of Visual Cognition (1985), Connections and
      Symbol (1988, with Jacques Mehler), and Lexical and Conceptual Semantics (1992,
      with Beth Levin). He was the recipient of the Early Career Award in 1984 and the
      Boyd McCandless Award in 1986 from the American Psychological Association, a
      Graduate Teaching Award from MIT in 1986, and the Troland Research Award from the
      National Academy of Sciences in 1993. His newest book, The Language Instinct,
      will be published by William Morrow & Company in January 1994. 

PMID- 23962334
TI  - Controlled manipulation of flexible carbon nanotubes through shape-dependent
      pushing by atomic force microscopy.
AB  - A systematic approach to manipulating flexible carbon nanotubes (CNTs) has been
      developed on the basis of atomic force microscope (AFM) based pushing. Pushing
      CNTs enables efficient transport and precise location of individual CNTs. A key
      issue for pushing CNTs is preventing defective distortion in repetitive bending
      and unbending deformation. The approach presented here controls lateral movement
      of an AFM tip to bend CNTs without permanent distortion. The approach
      investigates possible defects caused by tensile strain of the outer tube under
      uniform bending and radial distortion by kinking. Using the continuum beam model
      and experimental bending tests, dependency of maximum bending strain on the
      length of bent CNTs and radial distortion on bending angles at a bent point have
      been demonstrated. Individual CNTs are manipulated by limiting the length of bent
      CNTs and the bending angle. In our approach, multiwalled CNTs with 5-15 nm
      diameter subjected to bending deformation produce no outer tube breakage under
      uniform bending and reversible radial deformation with bending angles less than
      110 degrees . The lateral tip movement is determined by a simple geometric model
      that relies on the shape of multiwalled CNTs. The model effectively controls
      deforming CNT length and bending angle for given CNT shape. Experimental results
      demonstrate successful manipulation of randomly dispersed CNTs without visual
      defects. This approach to pushing can be extended to develop a wide range of CNT
      based nanodevice applications. 

PMID- 23962335
TI  - Molecular transport modulates the adaptive response of branched actin networks to
      an external force.
AB  - Actin networks are an integral part of the cytoskeleton of eukaryotic cells and
      play an essential role in determining cellular shape and movement. Understanding
      the underlying mechanism of actin network assembly is of fundamental importance.
      We developed in this work a minimal motility model and performed stochastic
      simulations to study mechanical regulation of the growth dynamics of lamellipodia
      like branched actin networks, characterized by various force-velocity relations.
      In such networks, the treadmilling process leads to a concentration gradient of G
      actin, and thus G-actin transport is essential to effective actin network
      assembly. We first explore how capping protein modulates force-velocity relations
      and then discuss how actin transport due to diffusion and facilitated transport
      such as advective flow tunes the growth dynamics of the branched actin network.
      Our work demonstrates the important role of molecular transport in determining
      the adaptive response of the actin network to an external force. 

PMID- 23962336
TI  - Arene-metal pi-complexation as a traceless reactivity enhancer for C-H arylation.
AB  - Current approaches to facilitate C-H arylation of arenes involve the use of
      either strongly electron-withdrawing substituents or directing groups. Both
      approaches require structural modification of the arene, limiting their
      generality. We present a new approach where C-H arylation is made possible
      without altering the connectivity of the arene via pi-complexation of a Cr(CO)3
      unit, greatly enhancing the reactivity of the aromatic C-H bonds. We apply this
      approach to monofluorobenzenes, highly unreactive arenes, which upon complexation
      become nearly as reactive as pentafluorobenzene itself in their couplings with
      iodoarenes. DFT calculations indicate that C-H activation via a concerted
      metalation-deprotonation transition state is facilitated by the predisposition of
      C-H bonds in (Ar-H)Cr(CO)3 to bend out of the aromatic plane. 

PMID- 23962337
TI  - Spindle and kinetochore associated complex subunit 1 regulates the proliferation
      of oral adenosquamous carcinoma CAL-27 cells in vitro.
AB  - BACKGROUND: The prognosis of oral squamous cell carcinoma is very poor due to
      local recurrence and metastasis. This study explores the molecular events
      involved in oral carcinoma with the goal of developing novel therapeutic
      strategies. The mitotic spindle is a complex mechanical apparatus required for
      the accurate segregation of sister chromosomes during mitosis. Spindle and
      kinetochore associated complex subunit 1 (SKA1) is a microtubule-binding
      subcomplex of the outer kinetochore that is essential for proper chromosome
      segregation. In recent years, much attention has been focused on determining how
      SKA proteins interact with each other, as well as their biological role in cancer
      cells. However, the precise role of SKA1 in oral carcinoma remains unknown.
      METHODS: In order to investigate the role of SKA1 in oral cancer, we employed
      lentivirus-mediated shRNA to silence SKA1 expression in the CAL-27 human oral
      adenosquamous carcinoma cell line. RESULTS: Depletion of SKA1 in CAL-27 cells
      significantly decreased cell proliferation, as determined by MTT and colony
      formation assays. These results strongly demonstrate that reduced SKA1 protein
      levels may cause inhibition of tumor formation. The shRNA-mediated depletion of
      SKA1 also led to G2/M phase cell cycle arrest and apoptosis. CONCLUSION: This is
      the first report to show that SKA1 plays an important role in the progression of
      oral adenosqamous carcinoma. Thus, silencing of SKA1 by RNAi might be a potential
      therapy for this disease.

PMID- 23962338
TI  - Synthesis, characterization, and photophysical properties of heteroleptic
      copper(I) complexes with functionalized 3-(2'-pyridyl)-1,2,4-triazole chelating
      ligands.
AB  - A new series of mononuclear copper(I) complexes (1-9) with functionalized 3-(2'
      pyridyl)-1,2,4-triazole chelating ligands, as well as the halide and/or phosphine
      ancillary ligands, have been synthesized. Complexes 1-9 were fully characterized
      by elemental analysis, NMR spectroscopy, mass spectroscopy, electronic absorption
      spectroscopy, fluorescence spectroscopy, cyclic voltammetry, and X-ray
      crystallography (1-8). They adopt a distorted tetrahedral configuration, and are
      considerably air-stable in solid state and in solution. All these Cu(I) complexes
      display a comparatively weak low-energy absorption in CH2Cl2 solution, assigned
      to charge-transfer transitions with appreciable MLCT character, as supported by
      TD-DFT studies. Cu(I) halide complexes 1-4 each shows bright solid-state emission
      at room temperature, although they are nonemissive in fluid solutions, in which
      the emission markedly depends on the halide and the substituent on the 2-pyridyl
      ring. Complexes 5-9 bearing 2-pyridyl functionalized 1,2,4-triazole and phosphine
      exhibit good photoluminescence properties in solution and solid states at ambient
      temperature, which are well-modulated via the alteration of the auxiliary
      phosphine ligand and the structural modification of 3-(2'-pyridyl)-1,2,4
      triazole. Interestingly, cationic complex 6 and neutral derivative 7 can readily
      be interconverted through the ring inversion of the 1,2,4-triazolyl regulated by
      the NH <-> N(-) transformation. 

PMID- 23962339
TI  - Trial of labor compared to repeat cesarean section in women with no other risk
      factors than a prior cesarean delivery.
AB  - OBJECTIVE: To compare outcomes with trial of labor after cesarean (TOLAC) or
      elective repeat cesarean delivery on maternal request (ERCD-MR). DESIGN:
      Prospective cohort study. SETTING: Danish university hospital. POPULATION: Women
      with TOLAC (n = 1161) and women with ERCD-MR (n = 622) between 2003 and 2010.
      Exclusion criteria were diabetes, two prior cesarean sections, index cesarean at
      a different hospital, a delivery after the index cesarean, twin gestation,
      gestational age <37(+0)  weeks and stillbirth. METHODS: Data were obtained from
      the Aarhus Birth Cohort database, which comprised prospective registration of the
      deliveries. MAIN OUTCOME MEASURES: Adverse neonatal outcomes, risk factors for
      emergency cesarean, and uterine rupture in case of TOLAC. RESULTS: TOLAC was
      associated with an increased risk of neonatal depression [odds ratio (OR) 3.6,
      95% confidence interval (CI) 1.1-19.1] and neonatal intensive care unit admission
      (adjusted OR 1.9, 95% CI 1.3-2.8). Within the TOLAC group 67% delivered
      vaginally. In the TOLAC group 1.3% (n = 15) of the women had a complete uterine
      rupture. None of these infants had sequelae after 12 months. Significant risk
      factors for emergency cesarean were no prior vaginal delivery (adjusted OR 1.8,
      95% CI 1.1-3.0), index emergency cesarean during labor (adjusted OR 3.0, 95% CI
      2.3-4.1), maternal age >=35 years (adjusted OR 1.9, 95% CI 1.3-2.8), pre
      pregnancy body mass index >=30 (adjusted OR 2.1, 95% CI 1.3-3.3), and birthweight
      4000-4499 g (adjusted OR 1.5, 95% CI 1.1-2.1). Uterine rupture was associated
      with the use of epidural analgesia (OR 2.2, 95% CI 1.1-4.9) and no prior vaginal
      delivery (p = 0.03). CONCLUSION: TOLAC is an acceptable individualized option for
      women without major risk factors.

PMID- 23962340
TI  - The incidence and health burden of earaches attributable to recreational swimming
      in natural waters: a prospective cohort study.
AB  - BACKGROUND: Earaches and outer ear infections are commonly associated with
      swimming. In this study, we estimated the excess risk and health burden of
      earaches due to swimming in natural fresh and marine waters using results from a
      survey of over 50,000 beachgoers at nine beaches across the United States.
      METHODS: Prospective cohort studies were conducted at four freshwater and five
      marine sites in the United States and Puerto Rico. Beach visitors were enrolled
      on summer weekends and holidays. Ten to twelve days after the beach visit,
      respondents answered questions about health symptoms, including earaches or ear
      infections experienced since the beach visit. Economic and physical burdens were
      also obtained. Fixed slope, random intercept (beach site) multivariate logistic
      regression models were used to estimate the relationship between head immersion
      swimming exposure and earaches. Model results were used to calculate excess risk
      for earaches attributable to swimming. RESULTS: The overall incidence of self
      reported earache was 1.6% in the 10-12 days after the beach visit. Earaches were
      more frequent in head immersion swimmers compared to non-swimmers for all beach
      sites and age groups. Earaches were unassociated with water sample measures of
      fecal contamination and turbidity. After adjustment for covariates, we calculated
      7.12 excess earaches among head immersion swimmers per 1,000 swimming events.
      Twenty-four percent of those with earache reported missing their regular
      activities; 28% visited a doctor; 4% visited the emergency room; and 31% and 40%
      used prescription and non-prescription medications, respectively. CONCLUSIONS:
      There are at least 128 million swimming events in natural waters annually. Such
      frequent exposures could result in 900,000 excess earaches, 260,000 visits to the
      doctor, 39,900 visits to the emergency room, nearly $4 million dollars in out-of
      pocket expenditures on prescription and over-the-counter medications, and close
      to 75,000 hours of clinician time. More accurate estimates of swimming exposure
      are needed to improve population burden and associated cost estimates.

PMID- 23962341
TI  - New dual-acting bronchodilator treatments for COPD, muscarinic antagonists and
      beta2 agonists in combination or combined into a single molecule.
AB  - INTRODUCTION: It has long been known that combining short-acting muscarinic
      antagonists and beta2 agonists produces additive effects on the lung function of
      patients with chronic obstructive pulmonary disease (COPD). Two closely related
      approaches to provide long-acting treatments offering the same functional are
      compared. AREAS COVERED: Six combinations of long-acting muscarinic antagonists
      and beta2 agonists are in clinical development, with five having progressed to
      Phase III studies or regulatory filing. Two dual-acting muscarinic
      antagonist/beta2 agonist molecules have progressed to Phase II clinical studies,
      with two more having been identified as in clinical development. EXPERT OPINION:
      Both approaches have been shown to provide clinically enhanced bronchodilator
      activity that is superior to that offered by the current standard treatments, but
      clinical results have yet to clearly demonstrate that these new combinations also
      provided an enhanced reduction in the frequency of disease exacerbations. At
      least one of these combinations should reach the market in 2014, so by the end of
      2015, it should be clear how useful such combinations may be in the treatment of
      COPD.

PMID- 23962342
TI  - The maintenance of sex: Ronald Fisher meets the Red Queen.
AB  - BACKGROUND: Sex in higher diploids carries a two-fold cost of males that should
      reduce its fitness relative to cloning, and result in its extinction. Instead,
      sex is widespread and clonal species face early obsolescence. One possible reason
      is that sex is an adaptation that allows organisms to respond more effectively to
      endless changes in their environment. The purpose of this study was to model
      mutation and selection in a diploid organism in an evolving environment and
      ascertain their support for sex. RESULTS: We used a computational approach to
      model finite populations where a haploid environment subjects a diploid host to
      endlessly evolving change. Evolution in both populations is primarily through
      adoption of novel advantageous mutations within a large allele space. Sex
      outcompetes cloning by two complementary mechanisms. First, sexual diploids adopt
      advantageous homozygous mutations more rapidly than clonal ones under conditions
      of lag load (the gap between the actual adaptation of the diploid population and
      its theoretical optimum). This rate advantage can offset the higher fecundity of
      cloning. Second, a relative advantage to sex emerges where populations are
      significantly polymorphic, because clonal polymorphism runs the risk of clonal
      interference caused by selection on numerous lines of similar adaptation. This
      interference extends allele lifetime and reduces the rate of adaptation. Sex
      abolishes the interference, making selection faster and elevating population
      fitness. Differences in adaptation between sexual and clonal populations increase
      markedly with the number of loci under selection, the rate of mutation in the
      host, and a rapidly evolving environment. Clonal interference in these
      circumstances leads to conditions where the greater fecundity of clones is unable
      to offset their poor adaptation. Sexual and clonal populations then either co
      exist, or sex emerges as the more stable evolutionary strategy. CONCLUSIONS: Sex
      can out-compete clones in a rapidly evolving environment, such as that
      characterized by pathogens, where clonal interference reduces the adaptation of
      clonal populations and clones adopt advantageous mutations more slowly. Since all
      organisms carry parasitic loads, the model is of potentially general
      applicability.

PMID- 23962344
TI  - Editorial.

PMID- 23962343
TI  - Kraft lignin chain extension chemistry via propargylation, oxidative coupling,
      and Claisen rearrangement.
AB  - Despite its aromatic and polymeric nature, the heterogeneous, stochastic, and
      reactive characteristics of softwood kraft lignin seriously limit its potential
      for thermoplastic applications. Our continuing efforts toward creating
      thermoplastic lignin polymers are now focused at exploring propargylation
      derivatization chemistry and its potential as a versatile novel route for the
      eventual utilization of technical lignins with a significant amount of molecular
      control. To do this, we initially report the systematic propargylation of
      softwood kraft lignin. The synthesized derivatives were extensively characterized
      with thermal methods (DSC, TGA), (1)H, (13)C, and quantitative (31)P NMR and IR
      spectroscopies. Further on, we explore the versatile nature of the lignin pendant
      propargyl groups by demonstrating two distinct chain extension chemistries; the
      solution-based, copper-mediated, oxidative coupling and the thermally induced,
      solid-state, Claissen rearrangement polymerization chemistries. Overall, we show
      that it is possible to modulate the reactivity of softwood kraft lignin via a
      combination of methylation and chain extension providing a rational means for the
      creation of higher molecular weight polymers with the potential for thermoplastic
      materials and carbon fibers with the desired control of structure-property
      relations. 

PMID- 23962345
TI  - In memorium.

PMID- 23962346
TI  - Sight of the hand in catching.

PMID- 23962347
TI  - Nausea and vomiting in pregnancy: associations with maternal gestational diet and
      lifestyle factors in the Norwegian Mother and Child Cohort Study.
AB  - OBJECTIVE: To investigate primarily the dietary intake, as well as demographics
      and selected lifestyle factors, of women experiencing nausea and vomiting in
      pregnancy, nausea only, or women who are symptom free. DESIGN: Prospective cohort
      study. SETTING: The Norwegian Mother and Child Cohort Study, a population-based
      pregnancy cohort. SAMPLE: Analyses were based on 51 675 Norwegian pregnancies.
      METHODS: Dietary intake was assessed by a self-reported food frequency
      questionnaire answered in the first trimester of pregnancy, as were data
      regarding nausea and vomiting. Chi-squared tests, one-way analysis of variance,
      and multiple linear regression were used. MAIN OUTCOME MEASURES: Nausea and
      vomiting in pregnancy (NVP), gestational weight gain (GWG), and dietary intake.
      RESULTS: We found that 17 070 (33%) women experienced NVP, 20 371 (39%)
      experienced only nausea, and 14 234 (28%) were symptom free. Women with NVP were
      younger and heavier at pregnancy onset, with the lowest GWG and highest energy
      intake during pregnancy, primarily from carbohydrates and added sugars, compared
      with the other groups (P < 0.001). In multiple linear regression analysis of GWG
      and group adjusted for body mass index (BMI), gestational length, smoking during
      pregnancy, and energy intake, a significant interaction was found between BMI and
      group (P < 0.001). A significant effect of group (P < 0.001) was found in all BMI
      strata, except among underweight women (P = 0.65). CONCLUSIONS: Our study
      suggests that women with NVP are characterised by high intakes of carbohydrates
      and added sugar, primarily from sugar-containing soft drinks. Whether higher
      intakes of carbohydrates are a response aimed to alleviate symptoms, or are
      actually provoking the condition, is not known.

PMID- 23962348
TI  - Synthesis of azole-enriched cyclic peptides by a clean solid-phase-based
      cyclization-cleavage strategy.
AB  - Naturally occurring azole-enriched cyclic peptides have broad biological and
      pharmacological activities. Previous synthetic efforts have mainly concentrated
      on the preparation of individual target molecules in solution phase. A solid
      phase-based cyclitive cleavage strategy was deployed here for efficient library
      synthesis of azole cyclopeptide derivatives, which is part of our continuous
      efforts for the characterization of potent modulators of multidrug resistance
      efflux proteins. Procedures were optimized to afford the azole cyclopeptides at
      high yield and purity, eliminating the need for any chromatographic purification
      steps. This development is ideal for high throughput library synthesis and
      screening and will facilitate the ultimate discovery of novel azole cyclopeptides
      with potent biological activities. 

PMID- 23962349
TI  - Happiness takes you right: the effect of emotional stimuli on line bisection.
AB  - Emotion recognition is mediated by a complex network of cortical and subcortical
      areas, with the two hemispheres likely being differently involved in processing
      positive and negative emotions. As results on valence-dependent hemispheric
      specialisation are quite inconsistent, we carried out three experiments with
      emotional stimuli with a task being sensitive to measure specific hemispheric
      processing. Participants were required to bisect visual lines that were delimited
      by emotional face flankers, or to haptically bisect rods while concurrently
      listening to emotional vocal expressions. We found that prolonged (but not
      transient) exposition to concurrent happy stimuli significantly shifted the
      bisection bias to the right compared to both sad and neutral stimuli, indexing a
      greater involvement of the left hemisphere in processing of positively connoted
      stimuli. No differences between sad and neutral stimuli were observed across the
      experiments. In sum, our data provide consistent evidence in favour of a greater
      involvement of the left hemisphere in processing positive emotions and suggest
      that (prolonged) exposure to stimuli expressing happiness significantly affects
      allocation of (spatial) attentional resources, regardless of the sensory
      (visual/auditory) modality in which the emotion is perceived and space is
      explored (visual/haptic). 

PMID- 23962350
TI  - A systematic review of interventions for children with cerebral palsy: state of
      the evidence.
AB  - AIM: The aim of this study was to describe systematically the best available
      intervention evidence for children with cerebral palsy (CP). METHOD: This study
      was a systematic review of systematic reviews. The following databases were
      searched: CINAHL, Cochrane Library, DARE, EMBASE, Google Scholar MEDLINE,
      OTSeeker, PEDro, PsycBITE, PsycINFO, and speechBITE. Two independent reviewers
      determined whether studies met the inclusion criteria. These were that (1) the
      study was a systematic review or the next best available; (2) it was a
      medical/allied health intervention; and (3) that more than 25% of participants
      were children with CP. Interventions were coded using the Oxford Levels of
      Evidence; GRADE; Evidence Alert Traffic Light; and the International
      Classification of Function, Disability and Health. RESULTS: Overall, 166 articles
      met the inclusion criteria (74% systematic reviews) across 64 discrete
      interventions seeking 131 outcomes. Of the outcomes assessed, 16% (21 out of 131)
      were graded 'do it' (green go); 58% (76 out of 131) 'probably do it' (yellow
      measure); 20% (26 out of 131) 'probably do not do it' (yellow measure); and 6% (8
      out of 131) 'do not do it' (red stop). Green interventions included
      anticonvulsants, bimanual training, botulinum toxin, bisphosphonates, casting,
      constraint-induced movement therapy, context-focused therapy, diazepam, fitness
      training, goal-directed training, hip surveillance, home programmes, occupational
      therapy after botulinum toxin, pressure care, and selective dorsal rhizotomy.
      Most (70%) evidence for intervention was lower level (yellow) while 6% was
      ineffective (red). INTERPRETATION: Evidence supports 15 green light
      interventions. All yellow light interventions should be accompanied by a
      sensitive outcome measure to monitor progress and red light interventions should
      be discontinued since alternatives exist.

PMID- 23962351
TI  - Bacterial septicaemia in prerecruit edible crabs, Cancer pagurus L.
AB  - Juvenile edible crabs, Cancer pagurus L., were surveyed from Mumbles Head and
      Oxwich Bay in South Wales, UK, and the number of heterotrophic bacteria and
      vibrios in the hemolymph was determined. The percentage of crabs with hemolymph
      containing bacteria was variable over the survey with higher numbers of animals
      affected in summer than in winter. Post-moult crabs contained significantly
      higher numbers of heterotrophic bacteria in the hemolymph than pre- and
      intermoult animals. Crabs with cuticular damage to the gills also had
      significantly higher numbers of bacteria in the hemolymph. Crabs were found to
      have a high prevalence of infection by the dinoflagellate, Hematodinium. Such
      animals had significantly fewer bacteria in the blood in comparison with
      Hematodinium-free animals. Of the 463 crabs surveyed, only 3 individuals had
      hemolymph containing 2000 + CFU mL(-1). Based on 16S rRNA gene sequences, two of
      these crabs contained a Vibrio pectenicida-like isolate, while the other had a
      mixed assemblage of vibrios. Although 59% of the crabs surveyed had culturable
      bacteria in the hemolymph, the majority only had small numbers (<2000 CFU mL(-1)
      ), suggesting that such infections may be of limited importance to the
      sustainability of the crab fishery in this region.

PMID- 23962353
TI  - A framework for chiropractic training in clinical preventive services.
AB  - The 2010 Patient Protection and Affordable Care Act provides incentives for both
      patients and providers to engage in evidence-based clinical preventive services
      recommended by the United States Preventive Services Task Force (USPSTF).
      Depending upon the application of the new health care act, Doctors of
      Chiropractic (DC) may be considered to be covered providers of many of these
      services. It is therefore essential that DCs' training prepare them to
      competently deliver them. The aim of this commentary is to describe a framework
      for training in clinical preventive services, based largely on the USPSTF
      recommendations, which could be readily integrated into existing DC educational
      programs. 

PMID- 23962354
TI  - A simple method to prevent the obstruction of post-tympanoplasty ventilation
      tubes.
AB  - The simultaneous insertion of a ventilation tube or grommet during tympanoplasty
      is a well-recognised practice among otologists. It is used to reverse atelectasis
      and to repneumatise the middle ear. A troublesome problem which can occur is post
      operative, intraluminal grommet obstruction by blood or viscous mucoid
      secretions. Routine post-operative use of eardrops may help prevent grommet
      obstruction but cannot be administered after tympanoplasty when the ear canal is
      packed with dressings for up to three weeks post-operatively. In this article, we
      describe a simple method to prevent post-tympanoplasty grommet obstruction.

PMID- 23962352
TI  - The chromosome cycle of prokaryotes.
AB  - In both eukaryotes and prokaryotes, chromosomal DNA undergoes replication,
      condensation-decondensation and segregation, sequentially, in some fixed order.
      Other conditions, like sister-chromatid cohesion (SCC), may span several
      chromosomal events. One set of these chromosomal transactions within a single
      cell cycle constitutes the 'chromosome cycle'. For many years it was generally
      assumed that the prokaryotic chromosome cycle follows major phases of the
      eukaryotic one: -replication-condensation-segregation-(cell division)
      decondensation-, with SCC of unspecified length. Eventually it became evident
      that, in contrast to the strictly consecutive chromosome cycle of eukaryotes, all
      stages of the prokaryotic chromosome cycle run concurrently. Thus, prokaryotes
      practice 'progressive' chromosome segregation separated from replication by a
      brief SCC, and all three transactions move along the chromosome at the same fast
      rate. In other words, in addition to replication forks, there are 'segregation
      forks' in prokaryotic chromosomes. Moreover, the bulk of prokaryotic DNA outside
      the replication-segregation transition stays compacted. I consider possible
      origins of this concurrent replication-segregation and outline the 'nucleoid
      administration' system that organizes the dynamic part of the prokaryotic
      chromosome cycle. 

PMID- 23962355
TI  - Honeymoon, medical treatment or big business? An analysis of the meanings of the
      term "reproductive tourism" in German and Israeli public media discourses.
AB  - BACKGROUND/INTRODUCTION: Infertile couples that travel to another country for
      reproductive treatment do not refer to themselves as "reproductive tourists".
      They might even be offended by this term. "Tourism" is a metaphor with hidden
      connotations. We will analyze these connotations in public media discourses on
      "reproductive tourism" in Israel and Germany. We chose to focus on these two
      countries since legal, ethical and religious restrictions give couples a similar
      motivation to travel for reproductive care, while the cultural backgrounds and
      conceptions of reproduction are different. RESULTS: Our research shows that the
      use of the metaphor "reproductive treatment" and its hidden messages depends on
      the writers' intention and the target population. Although the phenomenon of
      patients travelling for reproductive treatment can fit into the definitions of
      tourism, the term emphasizes aspects that do not reflect patients' reality. In
      both the German and the Israeli public media debate the term "reproductive
      tourism" is either used to criticize the economic aspects of the phenomenon or to
      attract patients as potential clients. CONCLUSIONS: Ethicists should be cautious
      when borrowing metaphors like "reproductive tourism" from the public debate. Our
      findings support Penning's suggestion to use instead an unloaded term like cross
      border reproductive care to describe the phenomenon in a more neutral way and to
      make it explicit whenever criticism is necessary.

PMID- 23962356
TI  - Functional magnetic resonance imaging of story listening in adolescents and young
      adults with Down syndrome: evidence for atypical neurodevelopment.
AB  - BACKGROUND: Previous studies have documented differences in neural activation
      during language processing in individuals with Down syndrome (DS) in comparison
      with typically developing individuals matched for chronological age. This study
      used functional magnetic resonance imaging (fMRI) to compare activation during
      language processing in young adults with DS to typically developing comparison
      groups matched for chronological age or mental age. We hypothesised that the
      pattern of neural activation in the DS cohort would differ when compared with
      both typically developing cohorts. METHOD: Eleven persons with DS (mean
      chronological age = 18.3; developmental age range = 4-6 years) and two groups of
      typically developing individuals matched for chronological (n = 13; mean age =
      18.3 years) and developmental (mental) age (n = 12; chronological age range = 4-6
      years) completed fMRI scanning during a passive story listening paradigm. Random
      effects group comparisons were conducted on individual maps of the contrast
      between activation (story listening) and rest (tone presentation) conditions.
      RESULTS: Robust activation was seen in typically developing groups in regions
      associated with processing auditory information, including bilateral superior and
      middle temporal lobe gyri. In contrast, the DS cohort demonstrated atypical
      spatial distribution of activation in midline frontal and posterior cingulate
      regions when compared with both typically developing control groups. Random
      effects group analyses documented reduced magnitude of activation in the DS
      cohort when compared with both control groups. CONCLUSIONS: Activation in the DS
      group differed significantly in magnitude and spatial extent when compared with
      chronological and mental age-matched typically developing control groups during a
      story listening task. Results provide additional support for an atypical pattern
      of functional organisation for language processing in this population.

PMID- 23962357
TI  - Restructuring of a model hydrophobic surface: Monte Carlo simulations using a
      simple coarse-grained model.
AB  - A lattice model is proposed to explain the restructuring of an ionic surfactant
      absorbed on a charged surface. When immersed in water, an ionic mica plate
      initially covered by a monolayer of surfactants rearranges to a surface
      inhomogeneously covered by patches of surfactant bilayer and bare mica. The model
      considers four species that can cover lattice sites of a surface. These species
      include (i) a surfactant molecule with its headgroup down, (ii) surfactant
      molecule with the headgroup up, (iii) a surfactant dimer arranged in a tail-to
      tail configuration, which is a part of a bilayer, and (iv) a mica lattice site
      covered by water. We consider that only nearest neighbors on the lattice interact
      and describe the interactions by an interaction matrix. Using this model, we
      perform Monte Carlo simulations and study how the structure of the inhomogeneous
      surface depends on the interaction between water covered lattice site and its
      neighboring surfactant species covered sites. We observe that when this
      interaction is absent, the system undergoes phase separation into a bilayer phase
      and mica surface covered with water. When this interaction is taken into account,
      patches of surfactant bilayer and water are present in our system. The
      interaction between mica surfaces covered by patches of ionic surfactants is
      studied in experiments to understand the nature of long-ranged "hydrophobic"
      forces. 

PMID- 23962359
TI  - Practical consideration of inserting intrauterine balloon during cesarean section
      for placenta previa.

PMID- 23962358
TI  - Hospital disaster preparedness as measured by functional capacity: a comparison
      between Iran and Sweden.
AB  - INTRODUCTION: Hospitals are expected to continue to provide medical care during
      disasters. However, they often fail to function under these circumstances.
      Vulnerability to disasters has been shown to be related to the socioeconomic
      level of a country. This study compares hospital preparedness, as measured by
      functional capacity, between Iran and Sweden. METHODS: Hospital affiliation and
      size, and type of hazards, were compared between Iran and Sweden. The functional
      capacity was evaluated and calculated using the Hospital Safety Index (HSI) from
      the World Health Organization. The level and value of each element was
      determined, in consensus, by a group of evaluators. The sum of the elements for
      each sub-module led to a total sum, in turn, categorizing the functional capacity
      into one of three categories: A) functional; B) at risk; or C) inadequate.
      RESULTS: The Swedish hospitals (n = 4) were all level A, while the Iranian
      hospitals (n = 5) were all categorized as level B, with respect to functional
      capacity. A lack of contingency plans and the availability of resources were
      weaknesses of hospital preparedness. There was no association between the level
      of hospital preparedness and hospital affiliation or size for either country.
      CONCLUSION: The results suggest that the level of hospital preparedness, as
      measured by functional capacity, is related to the socioeconomic level of the
      country. The challenge is therefore to enhance hospital preparedness in countries
      with a weaker economy, since all hospitals need to be prepared for a disaster.
      There is also room for improvement in more affluent countries.

PMID- 23962360
TI  - Antibacterial activity of Aquilaria crassna leaf extract against Staphylococcus
      epidermidis by disruption of cell wall.
AB  - BACKGROUND: Aquilaria crassna Pierre ex Lecomte has been traditionally used in
      Thailand for treatment of infectious diseases such as diarrhoea and skin diseases
      for a long time. The main objectives of this study were to examine antibacterial
      activity of the Aquilaria crassna leaf extract against Staphylococcus epidermidis
      and its underlying mechanism. The antioxidant activity and acute toxicity were
      studied as well. METHODS: Antioxidant activities were examined by FRAP, ABTS and
      DPPH scavenging methods. Antibacterial activity was conducted using disc
      diffusion assay and the minimum inhibitory concentration (MIC) was determined by
      dilution method. The minimum bactericidal concentration (MBC) was reported as the
      lowest concentration producing no growth of microbes in the subcultures.
      Morphological changes of the microbe were observed by scanning electron
      microscopy, while an inhibitory effect on biofilm formation was evaluated by
      phase contrast microscopic analysis. Bacterial cell wall integrity was assessed
      by transmission electron microscopy. Acute toxicity was conducted in accordance
      with the OECD for Testing of Chemicals (2001) guidelines. RESULTS: The extract
      exhibited considerable antioxidant activity. Staphylococcus epidermidis was
      susceptible to the extract with the MIC and MBC of 6 and 12 mg/ml, respectively.
      The extract caused swelling and distortion of bacterial cells and inhibited
      bacterial biofilm formation. Rupture of bacterial cell wall occurred after
      treated with the extract for 24 h. Acute toxicity test in mice showed no sign of
      toxicity or death at the doses of 2,000 and 15,000 mg/kg body weight. CONCLUSION:
      The aqueous extract of Aquilaria crassna leaves possesses an in vitro
      antibacterial activity against Staphylococcus epidermidis, with no sign of acute
      oral toxicity in mice, probably by interfering with bacterial cell wall synthesis
      and inhibiting biofilm formation.

PMID- 23962361
TI  - Volatiles fingerprint of Artemisia umbelliformis subsp. eriantha by headspace
      solid phase microextraction GC-MS.
AB  - Artemisia umbelliformis subsp. eriantha is a protected species, whose essential
      oil is used in liqueur industry. Volatile profiles of fresh leaves and flowers
      from wild plants in comparison with regenerated in vitro plants introduced in
      experimental fields within an Italian national park were evaluated by headspace
      solid phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS).
      The chromatographic profiles appear to be qualitatively similar. The content of
      thujones, the characteristic metabolites of this species, is comparable with that
      obtained by analysis of essential oils. Principal component analysis of the HS
      SPME-GC-MS data supports the possibility of differentiating scent blends of
      genetically identical plants, and even flowers and leaves from the same
      individual. HS-SPME-GC-MS is shown to be a very efficient method to analyse and
      to describe the pattern of components of A. umbelliformis subsp. eriantha
      cultivars' scents. It represents a rapid screening method highly recommended for
      the study of protected species, because it is non-destructive and it only
      requires small amounts of fresh material. 

PMID- 23962362
TI  - The ICMJE authorship criteria: a response from the editors.

PMID- 23962363
TI  - Application of permanents of square matrices for DNA identification in multiple
      fatality cases.
AB  - BACKGROUND: DNA profiling is essential for individual identification. In forensic
      medicine, the likelihood ratio (LR) is commonly used to identify individuals. The
      LR is calculated by comparing two hypotheses for the sample DNA: that the sample
      DNA is identical or related to a reference DNA, and that it is randomly sampled
      from a population. For multiple-fatality cases, however, identification should be
      considered as an assignment problem, and a particular sample and reference pair
      should therefore be compared with other possibilities conditional on the entire
      dataset. RESULTS: We developed a new method to compute the probability via
      permanents of square matrices of nonnegative entries. As the exact permanent is
      known as a #P-complete problem, we applied the Huber-Law algorithm to approximate
      the permanents. We performed a computer simulation to evaluate the performance of
      our method via receiver operating characteristic curve analysis compared with LR
      under the assumption of a closed incident. Differences between the two methods
      were well demonstrated when references provided neither obligate alleles nor
      impossible alleles. The new method exhibited higher sensitivity (0.188 vs. 0.055)
      at a threshold value of 0.999, at which specificity was 1, and it exhibited
      higher area under a receiver operating characteristic curve (0.990 vs. 0.959, P =
      9.6E-15). CONCLUSIONS: Our method therefore offers a solution for a
      computationally intensive assignment problem and may be a viable alternative to
      LR-based identification for closed-incident multiple-fatality cases.

PMID- 23962364
TI  - Responses of Anterior Superior Temporal Polysensory (STPa) Neurons to "Biological
      Motion" Stimuli.
AB  - Abstract Cells have been found in the superior temporal polysensory area (STPa)
      of the macaque temporal cortex that are selectively responsive to the sight of
      particular whole body movements (e.g., walking) under normal lighting. These
      cells typically discriminate the direction of walking and the view of the body
      (e.g., left profile walking left). We investigated the extent to which these
      cells are responsive under "biological motion" conditions where the form of the
      body is defined only by the movement of light patches attached to the points of
      limb articulation. One-third of the cells (25/72) selective for the form and
      motion of walking bodies showed sensitivity to the moving light displays. Seven
      of these cells showed only partial sensitivity to form from motion, in so far as
      the cells responded more to moving light displays than to moving controls but
      failed to discriminate body view. These seven cells exhibited directional
      selectivity. Eighteen cells showed statistical discrimination for both direction
      of movement and body view under biological motion conditions. Most of these cells
      showed reduced responses to the impoverished moving light stimuli compared to
      full light conditions. The 18 cells were thus sensitive to detailed form
      information (body view) from the pattern of articulating motion. Cellular
      processing of the global pattern of articulation was indicated by the
      observations that none of these cells were found sensitive to movement of
      individual limbs and that jumbling the pattern of moving limbs reduced response
      magnitude. A further 10 cells were tested for sensitivity to moving light
      displays of whole body actions other than walking. Of these cells 5/10 showed
      selectivity for form displayed by biological motion stimuli that paralleled the
      selectivity under normal lighting conditions. The cell responses thus provide
      direct evidence for neural mechanisms computing form from nonrigid motion. The
      selectivity of the cells was for body view, specific direction, and specific type
      of body motion presented by moving light displays and is not predicted by many
      current computational approaches to the extraction of form from motion. 

PMID- 23962365
TI  - Learning and maintaining saccadic accuracy: a model of brainstem-cerebellar
      interactions.
AB  - Abstract Saccadic accuracy requires that the control signal sent to the motor
      neurons must be the right size to bring the fovea to the target, whatever the
      initial position of the eyes (and corresponding state of the eye muscles).
      Clinical and experimental evidence indicates that the basic machinery for
      generating saccadic eye movements, located in the brainstem, is not accurate:
      learning to make accurate saccades requires cerebellar circuitry located in the
      posterior vermis and fastigial nucleus. How do these two circuits interact to
      achieve adaptive control of saccades? A model of this interaction is described,
      based on Kawato's principle of feedback-error-learning. Its three components were
      (1) a simple controller with no knowledge of initial eye position, corresponding
      to the superior colliculus; (2) Robinson's internal feedback model of the
      saccadic burst generator, corresponding to preoculomotor areas in the brain-stem;
      and (3) Albus's Cerebellar Model Arithmetic Computer (CMK), a neural net model of
      the cerebellum. The connections between these components were (I) the simple
      feedback controller passed a (usually inaccurate) command to the pulse generator,
      and (2) a copy of this command to the CMAC; (3) the CMAC combined the copy with
      information about initial eye position to (4) alter the gain on the pulse
      generator's internal feedback loop, thereby adjusting the size of burst sent to
      the motor neurons. (5) If the saccade were inaccurate, an error signal from the
      feedback controller adjusted the weights in the CMAC. It was proposed that
      connection (2) corresponds to the mossy fiber projection from superior colliculus
      to oculomotor vermis via the nucleus reticularis tegmenti pontis, and connection
      (5) to the climbing fiber projection from superior colliculus to the oculomotor
      vermis via the inferior olive. Plausible initialization values were chosen so
      that the system produced hypometric saccades (as do human infants) at the start
      of learning, and position-dependent hypermetric saccades when the cerebellum was
      removed. Simulations for horizontal eye movements showed that accurate saccades
      from any starting position could be learned rapidly, even if the error signal
      conveyed only whether the initial saccade were too large or too small. In
      subsequent tests the model adapted realistically both to simulated weakening of
      the eye muscles, and to intrasaccadic displacement of the target, thereby
      mimicking saccadic plasticity in adults. The architecture of the model may
      therefore offer a functional explanation of hitherto mysterious tectocerebellar
      projections, and a framework for investigating in greater detail how the
      cerebellum adaptively controls saccadic accuracy. 

PMID- 23962366
TI  - Duration of EEG and MEG alpha Suppression Increases with Angle in a Mental
      Rotation Task.
AB  - Abstract Electric and magnetic recordings of average power within the high a band
      (10-12 Hz) were made over the parietal and occipital areas of the scalp while
      subjects were engaged in the mental imagery task of Cooper and Shepard. The
      subject had to determine whether an abstract probe figure was identical to a
      memory figure presented earlier at a different orientation, or whether it was the
      mirror image of the memory figure. Alpha power was found to be suppressed while
      the subjects were engaged in the comparison, and the duration of suppression
      increased with the minimum rotation angle to achieve a match. Strong correlations
      between suppression duration and reaction time give further evidence that the
      visual cortex is engaged in the process of mental imagery. Moreover, for large
      rotation angles of the probe figures, where the task is markedly more difficult,
      a shift in the spatial pattern of suppression indicates some additional activity
      in left occipital areas. 

PMID- 23962367
TI  - Coding of Spatial Information in the Somatosensory System: Evidence from Patients
      with Neglect following Parietal Lobe Damage.
AB  - Abstract Unilateral parietal lobe damage, particularly in the right cerebral
      hemisphere, leads to neglect of stimuli on the contra lateral side. To determine
      the reference frame within which neglect operates in the somatosensory system, 11
      patients with unilateral neglect were touched simultaneously on the left and
      right side of the wrist of one hand. The hand was tested in both the palm up and
      the palm down position. Patients neglected the stimuli on the side of space
      contra lateral to the lesion regardless of hand position. These results indicate
      that point-localization in the somatosensory system is accomplished with respect
      to a spatially defined frame-of-reference and not strictly with respect to
      somatotopically defined coordinates. 

PMID- 23962368
TI  - Categorical versus Coordinate Spatial Processing: Effects of Blurring and
      Hemispheric Asymmetry.
AB  - Abstract The present experiment examined the effects of dioptric blurring on the
      performance of two different spatial processing tasks using the same visual
      stimuli. One task (the above/below, categorical task) required subjects to
      indicate whether a dot was above or below a horizontal line. The other task (the
      coordinate, near/far task) required subjects to indicate whether the dot was
      within 3 mm of the line. For both tasks, the stimuli on each trial were presented
      to either the right visual field and left hemisphere (RVF/LH) or the left Visual
      field and right hemisphere (LVF/RH). For the above/below task, dioptric blurring
      consistently increased reaction time (RT) and did so equally on LVF/RH and RVF/LH
      trials. Furthermore, there was no significant difference between the two visual
      fields for either clear or blurred stimuli. For the near/far task, dioptric
      blurring had no consistent effect on either RT or error rate for either visual
      field. On an initial block of trials, however, there were significantly fewer
      errors on LVF/RH than on RVF/LH trials, with the LVF/RH advantage being
      independent of whether the stimuli were clear or blurred. This initial LVF/RH
      advantage disappeared quickly with practice, regardless of whether the stimuli
      were clear or blurred. This pattern of results suggests that for both cerebral
      hemispheres, somewhat different aspects of visual information are relevant for
      categorical versus coordinate spatial processing and that the right hemisphere is
      superior to the left for coordinate (but not categorical) spatial processing. 

PMID- 23962369
TI  - Visual attention in children with perinatal brain injury: asymmetric effects of
      bilateral lesions.
AB  - Abstract The neural systems underlying visual attention have been well-documented
      in adults through studies examining the effects of brain lesions on specific
      attentional operations (Posner, Cohen, & Rafal, 1982). The questions of how this
      attentional system develops and how it is affected by disruption during
      development are only beginning to be addressed. In the present study, a covert
      orienting task (Posner et al., 1982) was administered to 33 children with
      bilateral perinatal injury to anterior, posterior, or diffuse brain regions and
      36 normal children to determine the effects of such injury on visual attention.
      Children with bilateral anterior lesions showed lateralized impairment indicating
      compromise of left hemisphere early attentional processes. In contrast, children
      with posterior lesions that typically disrupt attention in adults showed only
      general slowing, with no differences in right or left visual field performance or
      deficits in specific attentional operations. These results suggest that anterior
      brain regions play an important role in the development of visual attention, and
      that left hemisphere attentional processes are particularly affected by
      disruption of anterior function. 

PMID- 23962370
TI  - Interview: randy gallistel.

PMID- 23962371
TI  - Vision and visual dysfunction.

PMID- 23962372
TI  - A Review of Hemispheric Asymmetry: What's Right and What's Left.

PMID- 23962373
TI  - From animals to animats 2: proceedings of the second international conference on
      simulation of adaptive behavior.

PMID- 23962375
TI  - Aerobic oxidation of methanol to formic acid on Au8-: benchmark analysis based on
      completely renormalized coupled-cluster and density functional theory
      calculations.
AB  - The left-eigenstate completely renormalized coupled-cluster (CC) method with
      singles, doubles, and noniterative triples [CR-CC(2,3)] and a few representative
      density functional theory (DFT) approaches have been applied to methanol
      oxidation to formic acid on a Au8(-) cluster, which is a model for aerobic
      oxidations on gold nanoparticles. It is demonstrated that CR-CC(2,3) supports the
      previous exothermic reaction mechanism, placing the initial rate-determining
      transition state, which corresponds to hydrogen transfer from the methoxy species
      to the molecular oxygen, at about 20 kcal/mol above the reactants, less than 40
      kcal/mol above the O2 and CH3O(-) species coadsorbed on Au8(-), and considerably
      above the remaining two transition states along the reaction pathway. The DFT
      calculations using the previously exploited M06 hybrid functional show reasonable
      agreement with CR-CC(2,3), but B3LYP offers additional improvements in the
      description of the relevant activation energies. Pure functionals, including M06
      L, BP86, and TPSS, do not work well, significantly underestimating the activation
      barriers, but dispersion corrections, as in B97-D, bring the results closer to
      the M06 accuracy level. 

PMID- 23962374
TI  - Quantitative vibrational dynamics of the metal site in a tin porphyrin: an IR,
      NRVS, and DFT study.
AB  - We used a newer, synchrotron-based, spectroscopic technique (nuclear resonance
      vibrational spectroscopy, NRVS) in combination with a more traditional one
      (infrared absorption, IR) to obtain a complete, quantitative picture of the metal
      center vibrational dynamics in a six-coordinated tin porphyrin. From the NRVS
      (119)Sn site-selectivity and the sensitivity of the IR signal to (112)Sn/(119)Sn
      isotope substitution, we identified the frequency of the antisymmetric stretching
      of the axial bonds (290 cm(-1)) and all the other vibrations involving Sn.
      Experimentally authenticated density functional theory (DFT) calculations aid the
      data interpretation by providing detailed normal mode descriptions for each
      observed vibration. These results may represent a starting point toward the
      characterization of the local vibrational dynamics of the metallic site in tin
      porphyrins and compounds with related structures. The quantitative
      complementariness between IR, NRVS, and DFT is emphasized. 

PMID- 23962377
TI  - Prognostic factors for secondary recurrence of pleomorphic adenoma: a 20-year,
      retrospective study.
AB  - PURPOSE: To evaluate the results of treatment of parotid pleomorphic adenoma, and
      the risk factors for secondary recurrence. MATERIALS AND METHODS: Single-centre,
      retrospective study of 32 patients with pleomorphic adenoma recurrence managed
      between 1988 and 2008. RESULTS: The mean age at diagnosis of primary pleomorphic
      adenoma recurrence was 43.4 years. Twenty-eight per cent of patients had
      secondary recurrence; 32 per cent had undergone two or more surgical resections
      and external adjuvant radiotherapy. An age of less than 25 years was
      significantly associated with an earlier primary recurrence (p = 0.008). The most
      significant histopathological risk factor for secondary recurrence was the
      presence of a multifocal tumour (p = 0.019). Other histopathological criteria
      (i.e. cellularity and capsule rupture) were not significant. Radiotherapy was not
      associated with a decrease in recurrence. Nine per cent of patients progressed to
      malignancy. The main surgical complication was definitive facial palsy (14 per
      cent). CONCLUSION: Pleomorphic adenoma recurrence requires surgery, with greatly
      increased risk to the facial nerve. Resection with clear surgical margins is
      required, especially in young patients with multifocal tumours. Radiotherapy may
      delay second recurrence in cases of multifocal tumour.

PMID- 23962378
TI  - Clinical effectiveness and cost-effectiveness of depth of anaesthesia monitoring
      (E-Entropy, Bispectral Index and Narcotrend): a systematic review and economic
      evaluation.
AB  - BACKGROUND: It is important that the level of general anaesthesia (GA) is
      appropriate for the individual patient undergoing surgery. If anaesthesia is
      deeper than required to keep a patient unconscious, there might be increased risk
      of anaesthetic-related morbidity, such as postoperative nausea, vomiting and
      cognitive dysfunction. This may also prolong recovery times, potentially
      increasing health-care costs. If anaesthesia is too light, patients may not be
      fully unconscious and could be at risk of intraoperative awareness. OBJECTIVE:
      The objective of this report is to assess the clinical effectiveness and cost
      effectiveness of Bispectral Index (BIS), E-Entropy and Narcotrend technologies,
      each compared with standard clinical monitoring, to monitor the depth of
      anaesthesia in surgical patients undergoing GA. DATA SOURCES: A search strategy
      was developed and run on a number of bibliographic electronic databases including
      MEDLINE, EMBASE, The Cochrane Library and the Health Technology Assessment (HTA)
      database. For the systematic review of patient outcomes, databases were searched
      from the beginning of 2009 to November 2011 for studies of BIS (and then updated
      in February 2012), and from 1995 to November 2011 (and then updated in February
      2012) for studies of E-Entropy and Narcotrend. For the systematic review of cost
      effectiveness, searches were from database inception to November 2011 (an update
      search was performed in February 2012). REVIEW METHODS: The systematic review of
      patient outcomes followed standard methodology for evidence synthesis. A decision
      analytic model was developed to assess the cost-effectiveness of depth of
      anaesthesia monitoring compared with standard clinical observation. A simple
      decision tree was developed, which accounted for patients' risk of experiencing
      short-term anaesthetic-related complications in addition to risk of experiencing
      intraoperative awareness. RESULTS: Twenty-two randomised controlled trials
      comparing BIS, E-Entropy and Narcotrend with standard clinical monitoring were
      included in the systematic review of patient outcomes, alongside evidence from a
      recent Cochrane review. Six trials of patients classified with risk factors for
      intraoperative awareness were combined in a fixed-effect meta-analysis. The
      overall pooled Peto's odds ratio was 0.45 (95% confidence interval 0.25 to 0.81)
      in favour of BIS. However, there was statistically significant heterogeneity. The
      base-case cost per quality-adjusted life-year (QALY) for BIS compared with
      standard clinical monitoring ranged from L22,339 to L44,198 depending on patient
      subgroups (type of GA received; level of risk for awareness). For E-Entropy, base
      case estimates ranged from L14,421 to L31,430. For Narcotrend, estimates varied
      from a cost per QALY of L8033 to Narcotrend dominating standard clinical
      monitoring. LIMITATIONS: The analysis was limited by lack of clinical
      effectiveness data, particularly for E-Entropy and Narcotrend. CONCLUSIONS: The
      available evidence on the impact of the technologies on reducing the likelihood
      of intraoperative awareness is limited. However, there were reductions in general
      anaesthetic consumption and anaesthetic recovery times. The cost-effectiveness of
      depth of anaesthesia monitoring appears to be highly dependent on a number of
      factors, including probability of awareness. STUDY REGISTRATION: PROSPERO
      registration number CRD42011001834. FUNDING: The National Institute for Health
      Research Health Technology Assessment programme.

PMID- 23962379
TI  - MRI compatible small animal monitoring and trigger system for whole body
      scanners.
AB  - Performing magnetic resonance imaging (MRI) experiments with small animals
      requires continuous monitoring of vital parameters, especially the respiration
      rate. Clinical whole-body MR scanners represent an attractive option for
      preclinical imaging as dedicated animal scanners are cost-intensive in both
      investment and maintenance, thus limiting their availability. Even though
      impressive image quality is achievable with clinical MR systems in combination
      with special coils, their built-in physiologic monitoring and triggering units
      are often not suited for small animal imaging. In this work, we present a simple,
      MRI compatible low cost solution to monitor the respiration and heart rate of
      small animals in a clinical whole-body MR scanner. The recording and processing
      of the biosignals as well as the optimisation of the respiratory trigger
      generation is decribed. Additionally rat and mouse in-vivo MRI experiments are
      presented to illustrate the effectiveness of the monitoring and respiratory
      trigger system in suppressing motion artifacts. 

PMID- 23962380
TI  - Diversity of picoeukaryotes at an oligotrophic site off the Northeastern Red Sea
      Coast.
AB  - BACKGROUND: Picoeukaryotes are protists <= 3 MUm composed of a wide diversity of
      taxonomic groups. They are an important constituent of the ocean's microbiota and
      perform essential ecological roles in marine nutrient and carbon cycles. Despite
      their importance, the true extent of their diversity has only recently been
      uncovered by molecular surveys that resulted in the discovery of a substantial
      number of previously unknown groups. No study on picoeukaryote diversity has been
      conducted so far in the main Red Sea basin-a unique marine environment
      characterized by oligotrophic conditions, high levels of irradiance, high
      salinity and increased water temperature. RESULTS: We sampled surface waters off
      the coast of the northeastern Red Sea and analyzed the picoeukaryotic diversity
      using Sanger-based clone libraries of the 18S rRNA gene in order to produce high
      quality, nearly full-length sequences. The community captured by our approach was
      dominated by three main phyla, the alveolates, stramenopiles and chlorophytes;
      members of Radiolaria, Cercozoa and Haptophyta were also found, albeit in low
      abundances. Photosynthetic organisms were especially diverse and abundant in the
      sample, confirming the importance of picophytoplankton for primary production in
      the basin as well as indicating the existence of numerous ecological micro-niches
      for this trophic level in the upper euphotic zone. Heterotrophic organisms were
      mostly composed of the presumably parasitic Marine Alveolates (MALV) and the
      presumably bacterivorous Marine Stramenopiles (MAST) groups. A small number of
      sequences that did not cluster closely with known clades were also found,
      especially in the MALV-II group, some of which could potentially belong to novel
      clades. CONCLUSIONS: This study provides the first snapshot of the picoeukaryotic
      diversity present in surface waters of the Red Sea, hence setting the stage for
      large-scale surveying and characterization of the eukaryotic diversity in the
      entire basin. Our results indicate that the picoeukaryotic community in the
      northern Red Sea, despite its unique physiochemical conditions (i.e. increased
      temperatures, increased salinity, and high UV irradiance) does not differ vastly
      from its counterparts in other oligotrophic marine habitats.

PMID- 23962381
TI  - Relationships between sensory evaluations of beef tenderness, shear force
      measurements and consumer characteristics.
AB  - The supply of tender beef is an important challenge for the beef industry.
      Knowledge about the profile of consumers who are more optimistic or more accurate
      in their tenderness evaluations is important for product development and beef
      marketing purposes. Central location tests of beef steaks were performed in
      Norway and Belgium (n=218). Instrumental and sensorial tenderness of three
      muscles from Belgian Blue and Norwegian Red cattle was reported. Consumers who
      are optimistically evaluating tenderness were found to be more often male, less
      food neophobic, more positive towards beef healthiness, and showed fewer concerns
      about beef safety. No clear profile emerged for consumers who assessed tenderness
      similar to shear force measurements, which suggests that tenderness is mainly
      evaluated subjectively. The results imply a window of opportunities in tenderness
      improvements, and allow targeting a market segment which is less critical towards
      beef tenderness. 

PMID- 23962382
TI  - Respiratory uptake kinetics of neutral hydrophobic organic chemicals in a marine
      benthic fish, Pseudopleuronectes yokohamae.
AB  - We investigated the respiratory uptake kinetics of polychlorinated biphenyls
      (PCBs), organohalogen pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs),
      and 2,2',4,4'-tetrabrominated diphenyl ether (BDE #47) in a marine benthic fish,
      Pseudopleuronectes yokohamae. The respiratory uptake efficiencies (EW) of the
      chemicals, of which there have been no reports for the majority of persistent
      organic pollutants (POPs), were obtained by measuring the respiratory uptake rate
      constants (k1) and the oxygen consumption rates of fish. Fish were exposed to
      water in which these chemicals were dissolved at environmentally relevant
      concentrations for 28 d, followed by 168 d of depuration in clean seawater. The
      k1 and EW values for 99 compounds were obtained, and they ranged from 2000 to
      42000 L kg-lipid(-1) d(-1) and from 0.060 to 1.3, respectively. The EW values of
      the chemicals, except for PAHs, tended to increase with increasing values of the
      log octanol-water partition coefficients (KOW) of the chemicals up to a log KOW
      of 5. For log KOW in the range 3-5, the EW values in this study were much lower
      than those in a published study (about one-third). As a result of analysis by a
      two-phase resistance model, the resistance of transport rates to the lipid phase
      in this study was lower than was the case in the published study. These findings
      indicate that the EW predicted by the published study for log KOW in the range 3
      5 may differ among fish species and water temperature, and further study is
      needed.

PMID- 23962383
TI  - Impact of carbon, oxygen and sulfur content of microscale zerovalent iron
      particles on its reactivity towards chlorinated aliphatic hydrocarbons.
AB  - Zerovalent iron (ZVI) abiotically degrades several chlorinated aliphatic
      hydrocarbons (CAHs) via reductive dechlorination, which offers perspectives for
      in situ groundwater remediation applications. The difference in reactivity
      between ZVI particles is often linked with their specific surface area. However,
      other parameters may influence the reactivity as well. Earlier, we reported for a
      set of microscale zerovalent iron (mZVI) particles the disappearance kinetic of
      different CAHs which were collected under consistent experimental conditions. In
      the present study, these kinetic data were correlated with the carbon, oxygen and
      sulfur content of mZVI particles. It was confirmed that not only the specific
      surface area affects the disappearance kinetic of CAHs, but also the chemical
      composition of the mZVI particles. The chemical composition, in addition,
      influences CAHs removal mechanism inducing sorption onto mZVI particles instead
      of dechlorination. Generally, high disappearance kinetic of CAHs was observed for
      particles containing less oxygen. A high carbon content, on the other hand,
      induced nonreactive sorption of the contaminants on the mZVI particles. To obtain
      efficient remediation of CAHs by mZVI particles, this study suggested that the
      carbon and oxygen content should not exceed 0.5% and 1% respectively. Finally,
      the efficiency of the mZVI particles may be improved to some extent by enriching
      them with sulfur. However, the impact of sulfur content on the reactivity of mZVI
      particles is less pronounced than that of the carbon and oxygen content. 

PMID- 23962384
TI  - 'No-one actually goes to a shop and buys them do they?': attitudes and behaviours
      regarding illicit tobacco in a multiply disadvantaged community in England.
AB  - AIMS: To explore attitudes towards, and experience of, illicit tobacco usage in a
      disadvantaged community against a backdrop of austerity and declining national
      trends in illicit tobacco use. DESIGN: Qualitative study using 10 focus groups.
      SETTING: Multiply disadvantaged community in Nottingham, United Kingdom.
      PARTICIPANTS: Fifty-eight smokers, ex- and non-smokers aged 15-60 years.
      MEASUREMENTS: Focus group topic guides. FINDINGS: There was high awareness and
      use of illegal tobacco sources, with 'fag houses' (individuals selling cigarettes
      from their own homes) being particularly widespread. Rather than being regarded
      as marginal behaviour, buying illicit tobacco was perceived as commonplace, even
      where products were known to be counterfeit. Smokers' willingness to smoke
      inferior 'nasty' counterfeit products may be testament to their need for cheap
      nicotine. Illicit tobacco was seen to be of mutual benefit to both user (because
      of its low cost) and seller (because it provided income and support for the local
      economy). Illicit tobacco sellers were generally condoned, in contrast with the
      government, which was blamed for unfair tobacco taxation, attitudes possibly
      heightened by the recession. Easy access to illicit tobacco was seen to
      facilitate and sustain smoking, with the main concern being around underage
      smokers who were perceived to be able to buy cheap cigarettes without challenge.
      CONCLUSIONS: National strategies to reduce illicit tobacco may have limited
      impact in communities during a recession and where illicit trade is part of the
      local culture and economy. There may be potential to influence illicit tobacco
      use by building on the ambivalence and unease expressed around selling to
      children.

PMID- 23962385
TI  - Iran's disaster risk: now is the time for community-based public health
      preparedness.
AB  - The Bandar Bushehr, Iran earthquake of April 9, 2013 gravely illustrates how
      disaster-prone areas of the world are compounding their risk of disaster and
      major public health emergencies when there is a geographical convergence of
      natural and technological hazards. Scientists must emphasize to policy makers
      that ever-increasing regional industrialization and the broader introduction of
      nuclear facilities, especially in the Middle East, must parallel sound prevention
      and community-level public health preparedness planning.

PMID- 23962386
TI  - Neuromuscular response to varying pressures created by tightness of restriction
      cuff.
AB  - Variation in regional body composition between genders may change the degree of
      pressure created by the tightness of cuff used during blood flow restriction
      training resulting in changes in the level of neuromuscular activation. This
      study investigates the effects of tightness of cuff and skin and subcutaneous fat
      thickness on electromyography (EMG) amplitude (RMS) and median frequency (MDF)
      during exercises and strength testing. Subjects performed knee-extension
      exercises with varying tightness of cuff while using EMG to measure changes in
      neuromuscular response. EMG RMS was significantly affected by tightness of cuff
      and skin and subcutaneous fat thickness. The strongest individual variable for
      the changes in MDF was also skin and subcutaneous-fat thickness. The changes in
      EMG response due to tightness of cuff and the effect of skin and subcutaneous fat
      thickness on tightness of cuff prove the importance of details on BFR protocol
      and leg composition on neuromuscular function during BFR exercises. 

PMID- 23962387
TI  - Evidence for genetic linkage between a polymorphism in the GNAS gene and malaria
      in South Indian population.
AB  - The complex imprinted GNAS locus which encodes G-alpha subunit (Galphas) is
      involved in a number of G-protein coupled signaling pathways in eukaryotic cells.
      Erythrocyte invasion by Plasmodium falciparum parasites is significantly
      regulated by protein of GNAS gene. This study was designed to evaluate the
      association between single nucleotide polymorphisms (SNPs) present in GNAS locus
      and susceptibility to malaria. In this case control study, individuals affected
      by P. falciparum malaria (n=230), Plasmodium vivax malaria (n=230) and normal
      controls (n=230) were tested for the association of eighteen (18) known SNPs to
      evaluate their role in the onset of the disease. There was no significant
      difference in genotype frequencies of all the SNPs tested between P. falciparum
      and P. vivax affected individuals. However, when Bonferroni correction for
      multiple comparisons were performed as a control, our results demonstrated
      alleles and genotypes of rs7121: C>T (NC_000020.10:g.57478807C>T), a silent
      polymorphism situated in the exon 5, were significantly (p<0.05) associated with
      susceptibility to malaria in the South Indians participants. Our results
      demonstrate that population specific polymorphisms that exist in GNAS gene may
      alter the risk of occurrence of malaria. 

PMID- 23962388
TI  - Vector competence of Aedes albopictus and Aedes aegypti (Diptera: Culicidae) for
      DEN2-43 and New Guinea C virus strains of dengue 2 virus.
AB  - The vector competence of Aedes albopictus and Aedes aegypti with regard to DEN2
      43 and New Guinea C (NGC) virus strains of Dengue 2 viruses was assessed and
      compared. The infection and dissemination rate and distribution of DEN2-43
      antigens in orally infected Ae. albopictus was investigated using the reverse
      transcription polymerase chain reaction and an indirect immunofluorescence assay.
      To better understand the initial infection, dissemination and transmission of
      these viral strains in vector mosquitoes, Ae. albopoictus and Ae. aegypti were
      fed an artificial blood meal containing either the DEN2-43 or NGC strain. There
      was no significant difference in the infection and dissemination rates of DEN2-43
      and NGC virus strains in Ae. albopictus, however, Ae. aegypti was more
      susceptible to infection by NGC than DEN2-43 vrius strain. Ae. albopictus
      mosquitoes infected with the NGC strain developed a higher percentage of midgut
      infections than those infected with the DEN2-43 strain (t=2.893, df=7, P=0.024).
      Approximately 26.7% of midgut samples were positive for the NGC antigen 5 days
      after infection, and 80% of mosquitoes had infected midgets after 15 days. The
      NGC antigen first became evident in mosquito salivary glands on Day 5, and 40% of
      mosquitoes had infected salivary by Day 9. In contrast, the DEN2-43 antigen first
      became evident in salivary glands on Day 7. The infection rate of NGC and DEN2-43
      virus strains in salivary glands were similar. These results indicate that Ae.
      albopictus and Ae. aegypti are moderately competent vectors for the DEN2-43
      virus, which could provide basic data for the epidemiology study of dengue fever
      in China. 

PMID- 23962389
TI  - Microgeographical study of insecticide resistance in Triatoma infestans from
      Argentina.
AB  - Chagas disease is a chronic parasitic infection restricted to America where it is
      currently estimated that 90 million people are at risk of acquiring the
      infection. Chemical control with pyrethroid insecticides has been effective to
      reduce disease transmission in several areas of the Southern Cone, although
      insecticide resistance has evolved and diminished the campaigns' results.
      Considering previous reports on the different levels of resistance between
      Triatoma infestans from different geographical areas, the objective of this work
      was to determine if T. infestans populations are toxicologically structured
      within localities. Response to the insecticide was measured and compared between
      houses of two Argentine localities. Different toxicity of deltamethrin was
      detected between dwellings of Chaco province, accounting for both susceptible and
      resistant houses within the same locality. However no difference was found among
      houses of Salta province. The results obtained in this work suggest that
      geographical structure is present not only at the between localities level, but
      also at the microgeograhical level. 

PMID- 23962390
TI  - Fluoxetine enhances Brain Derived Neurotropic Factor Serum Concentration and
      Cognition in Patients with Vascular Dementia.
AB  - Selective serotonin reuptake inhibitors (SSRIs) improve cognition in patients
      with stroke and increase the expression of brain-derived neurotrophic factor
      (BDNF) in the rat hippocampus. However, the effects of SSRIs on cognition and
      BDNF level in vascular dementia (VaD) patients are largely unknown. We performed
      an open-label study to investigate the effects of fluoxetine, a selective
      serotonin reuptake inhibitor, on mini-mental state examination (MMSE) score and
      serum BDNF level in VaD patients. Fifty VaD patients were randomly allocated to
      receive fluoxetine (20 mg/d; n = 25) or no fluoxetine (control group; n = 25) for
      12 weeks. Both groups received secondary prevention of stroke. Baseline serum
      BDNF level correlated with MMSE score (r = 0.326, p = 0.021). MMSE score
      increased in the fluoxetine group (15.1 +/- 3.0 at baseline vs. 16.1 +/- 2.9 at
      week 12, p = 0.0004) but not in the control group (15.7 +/- 2.6 vs. 15.8 +/- 2.7,
      p = 0.566). Serum BDNF level increased in the fluoxetine group (21.2 +/- 3.2
      ng/ml at baseline vs. 25.7 +/- 4.0 ng/ml at week 12, p < 0.001) but not in the
      control group (21.4 +/- 5.8 ng/ml vs. 21.5 +/- 6.9 ng/ml, p = 0.921). In the
      fluoxetine group, the increase in serum BDNF level correlated with the increase
      in MMSE score (r = 0.413, p = 0.04). The utility of SSRIs during cognitive
      recovery of VaD patients requires further investigation. BDNF may play an
      important role in cognitive recovery. (Trial registration: chictr.org,
      Identifier: ChiCTR-TRC-12002247).

PMID- 23962391
TI  - Reply: Cesarean hysterectomy for placenta previa accreta; extrapolating measures
      may have merits for ordinary obstetricians.

PMID- 23962392
TI  - Tonsil tie simulator.
AB  - BACKGROUND: The surgical trainee has to acquire surgical skills in an era of
      reduced training hours and greater demands for efficient use of operating theatre
      time. Many surgical specialties are utilising model and simulation-based training
      to provide safe, low-pressure training opportunities for today's trainee. METHOD
      AND RESULTS: This paper describes a simple, relatively inexpensive tonsillectomy
      model that enables the practice of tonsil removal and ligation of bleeding
      vessels. The model is beneficial for the patient, trainee and trainer.
      CONCLUSION: The pseudo mouth and active bleeding components of this model provide
      the trainee with a relatively inexpensive, realistic model with which to gain
      confidence and competence in the skill of ligating tonsillar blood vessels with a
      tonsil tie.

PMID- 23962394
TI  - Genital chronic GVHD in men after hematopoietic stem cell transplantation: a
      single-center cross-sectional analysis of 155 patients.
AB  - We assessed the prevalence and clinical features of genital skin changes in men
      after allogeneic hematopoietic stem cell transplantation (HSCT) and evaluated the
      correlation between genital chronic graft-versus-host disease (cGVHD) and other
      manifestations of cGVHD as well as sexual issues. In a cross-sectional cohort
      study, 155 male recipients alive 1 year or more after HSCT were assessed during
      their annual follow-up evaluation. Correlation between genital skin changes and
      other cGVHD manifestations was evaluated, and post-transplantation sexual
      contentment and sexual functioning were assessed by 2 self-assessment
      questionnaires, including the 5-item version of the International Index of
      Erectile Function (IIEF-5) and the modified Brief Sexual Symptom Checklist
      (mBSSC). Median time between HSCT and genital examination was 5.9 years (range, 1
      to 30.3 years). Thirty-one of 155 patients (20%) presented with genital skin
      changes. Twenty-one of those (13%) presented clinically inflammatory genital skin
      changes considered as genital cGVHD: 12 had inflammatory (noninfectious)
      balanoposthitis, 6 had lichen sclerosis-like lesions, 5 had phimosis, and 2
      patients had more than 1 feature. Patients with inflammatory genital skin changes
      had a significantly higher coincidence of oral (P < .0001), ocular (P < .002),
      and/or cutaneous cGVHD (P < .026) when compared with patients without genital
      lesions. The rate of IIEF-5 questionnaire response was 59% (91 of 155). Among
      them, 67% reported erectile dysfunction. Erectile dysfunction was significantly
      more frequent in patients with genital cGVHD (P = .0075). Seventy-five of 155
      patients (48%) answered the mBSSC questionnaire. Only 40% of them reported sexual
      contentment. Genital skin changes in male recipients after allogeneic HSCT are
      frequent and seem to be an under-reported relevant late effect. Inflammatory
      genital skin changes can be considered as a form of genital cGVHD often
      associated with manifestations of extragenital mucocutaneous cGVHD. 

PMID- 23962395
TI  - Pathogen inactivation of whole blood and red cell components: an overview of
      concept, design, developments, criteria of acceptability and storage lesion.
AB  - Multilayer preventative strategies have been instituted to enhance transfusion
      safety for patients in need of critical blood components. Presently blood safety
      is at its highest levels, with the implementation of precautionary/preventative
      measures against vCJD, bacterial and viral contamination of the blood supply. The
      implementation of these strategies together with advances in automation and
      computerization led to significant improvements in standardisation for
      transfusion practices. These include validation, verification, adherence to GLP
      and GMP and other regulatory requirements. In most European countries, universal
      prestorage leukodepletion is routine practice. In France proactive pathogen
      inactivation treatments [PITs] have been implemented emphasizing patient safety.
      This at least conceptually reduces the risk of transfusing viable WBCs, emerging
      bacteria and viruses, all with potential transfusion complications. In the UK,
      prion removal filters for red cell products are used selectively for special
      groups of patients. Some research establishments are exploring the potential
      impact of pathogen inactivation of whole blood or red cell components, using the
      new generation of S-303 PIT and the prion removal filters in combination. It
      needs to be determined whether such a combined strategy, applied synergistically,
      enhances red cell transfusion safety without compromising the overall criteria of
      acceptability. It is necessary to critically examine the impact of a new
      generation of PIT technologies, which may exacerbate the red cell storage lesion
      and cause the development of undesirable antibodies in the recipient. The
      development of innovative laboratory tools is vital to study impacts of these
      measures on the quality of stored blood and their clinical outcome. The ultimate
      aim of red cell transfusion is to provide oxygen enriched red blood cells to the
      microcirculations and tissues. Definitive studies are needed to establish the
      potential unforeseen negative long term toxicity, overall efficacy/quality and
      the clinical outcome of treated stored blood. 

PMID- 23962393
TI  - Systemic sclerosis sera affect fibrillin-1 deposition by dermal blood
      microvascular endothelial cells: therapeutic implications of cyclophosphamide.
AB  - INTRODUCTION: Systemic sclerosis (SSc) is a connective tissue disorder
      characterized by endothelial cell injury, autoimmunity and fibrosis. The
      following three fibrillin-1 alterations have been reported in SSc. (1) Fibrillin
      1 microfibrils are disorganized in SSc dermis. (2) Fibrillin-1 microfibrils
      produced by SSc fibroblasts are unstable. (3) Mutations in the FBN1 gene and anti
      fibrillin-1 autoantibodies have been reported in SSc. Fibrillin-1 microfibrils,
      which are abundantly produced by blood and lymphatic microvascular endothelial
      cells (B-MVECs and Ly-MVECs, respectively), sequester in the extracellular matrix
      the latent form of the potent profibrotic cytokine transforming growth factor
      beta (TGF-beta). In the present study, we evaluated the effects of SSc sera on
      the deposition of fibrillin-1 and microfibril-associated glycoprotein 1 (MAGP-1)
      and the expression of focal adhesion molecules by dermal B-MVECs and Ly-MVECs.
      METHODS: Dermal B-MVECs and Ly-MVECs were challenged with sera from SSc patients
      who were treatment-naive or under cyclophosphamide (CYC) treatment and with sera
      from healthy controls. Fibrillin-1/MAGP-1 synthesis and deposition and the
      expression of alphavbeta3 integrin/phosphorylated focal adhesion kinase and
      vinculin/actin were evaluated by immunofluorescence and quantified by
      morphometric analysis. RESULTS: Fibrillin-1 and MAGP-1 colocalized in all
      experimental conditions, forming a honeycomb pattern in B-MVECs and a dense mesh
      of short segments in Ly-MVECs. In B-MVECs, fibrillin-1/MAGP-1 production and
      alphavbeta3 integrin expression significantly decreased upon challenge with sera
      from naive SSc patients compared with healthy controls. Upon challenge of B-MVECs
      with sera from CYC-treated SSc patients, fibrillin-1/MAGP-1 and alphavbeta3
      integrin levels were comparable to those of cells treated with healthy sera. Ly
      MVECs challenged with SSc sera did not differ from those treated with healthy
      control sera in the expression of any of the molecules assayed. CONCLUSIONS:
      Because of the critical role of fibrillin-1 in sequestering the latent form of
      TGF-beta in the extracellular matrix, its decreased deposition by B-MVECs
      challenged with SSc sera might contribute to dermal fibrosis. In SSc, CYC
      treatment might limit fibrosis through the maintenance of physiologic fibrillin-1
      synthesis and deposition by B-MVECs.

PMID- 23962396
TI  - Tetany by transfusion of small volume of blood: a rare case report.
AB  - A requisition for two units of packed red blood cells was received for a 54 year
      female, known case of genitourinary carcinoma. After transfusion of approximately
      15-20 ml of blood, a call was received from resident in charge of radiotherapy
      ward stating that patient had clenching of hands along with circumoral tingling
      and paresthesias in her limbs. Her investigations showed decreased serum
      potassium and calcium levels but serum magnesium levels were not available.
      Multiple electrolyte disturbances probably precipitated tetany even by small
      volume of blood transfusion. We therefore recommend careful monitoring of
      electrolytes, including magnesium, before starting blood transfusion.

PMID- 23962397
TI  - Lymphoma studies by the Australasian Leukaemia and Lymphoma Group.
AB  - The Australasian Leukaemia and Lymphoma Group (ALLG) can trace its origins to
      1973. It now encompasses virtually all the major hospitals in Australia and New
      Zealand that treat leukaemias and lymphomas. Over the years the Group as a whole,
      and members individually, have participated in many clinical treatment trials for
      aggressive lymphomas. Initially trials were conceived and carried out locally,
      but in recent years, in addition to continuing its own studies, the Group has
      been a major contributor to international trials including two that have been
      particularly influential, known as MInT and CORAL. The MInT study confirmed the
      value of adding rituximab to standard chemotherapy for aggressive lymphomas;
      CORAL helped define optimum methods of autografting for relapse. The ALLG has
      contributed and continues to contribute to the improving outcome for patients
      with aggressive lymphomas. 

PMID- 23962398
TI  - Anti-Leishmania antibodies in blood donors from the Midwest region of Brazil.
AB  - The aim of the study was to detect asymptomatic infection by Leishmania sp. in
      blood donors. Serum samples (430) were tested by Immunofluorescent Antibody Test,
      and an interview with the blood donors was carried out. Antibodies were detected
      in 15.6% of samples. The variables associated with the infection were: origin of
      the donor, presence of builds, parks or squares, sick dog in the neighborhood,
      and neighboring with leishmaniasis. It was observed association between origin of
      donors and the presence of sick dog. It is important a careful screening of
      donors, due to the risk of infection through blood transfusion. 

PMID- 23962399
TI  - A novel and other bioactive secondary metabolites from a marine fungus
      Penicillium oxalicum 0312F1.
AB  - A new compound 2-(4-hydroxybenzoyl) quinazolin-4(3H)-one (1) and four known
      compounds were isolated from a marine fungus Penicillium oxalicum 0312F1. The
      structure of the new compound 1 was elucidated based on the spectroscopic
      analysis. Bioactivity assays showed that 2-(4-hydroxybenzyl) quinazolin-4(3H)-one
      (2) and methyl 4-hydroxyphenylacetate (5) had potent inhibitory activity against
      tobacco mosaic virus (TMV), and the new compound 1 had moderate inhibitory
      activity against TMV and human gastric cancer cell SGC-7901. 

PMID- 23962400
TI  - A brisk walk, compared with being sedentary, reduces attentional bias and
      chocolate cravings among regular chocolate eaters with different body mass.
AB  - Poor self-regulation of high energy snacking has been linked to weight gain.
      Physical activity can acutely reduce chocolate consumption and cravings but the
      effects on attentional bias (AB) are unknown. The study aimed to test the effects
      of exercise among normal and overweight/obese individuals during temporary and
      longer abstinence. Participants were 20 normal and 21 overweight regular female
      chocolate eaters (after 24 h abstinence), and 17 females (after >=1 week
      abstinence during Lent). They were randomly assigned to engage in 15 min brisk
      walking or rest, on separate days. AB was assessed using an adapted dot probe
      task pre and post-treatment at each session, with chocolate/neutral paired images
      presented for 200 ms (initial AB; IAB) or 1000 ms (maintained AB; MAB). Chocolate
      craving was assessed pre, during, immediately after, and 5 min and 10 min after
      treatment, using a 0-100 visual analogue score. Three-way mixed ANOVAs revealed
      that there was no significant interaction effect between group (i.e., BMI status,
      or abstinence status) and condition * time for craving and AB to chocolate cues.
      Fully repeated 2-way ANOVAS revealed a significant condition * time interaction
      for IAB (F(1,57)=6.39) and chocolate craving (F(2.34,133.19)=14.44). After
      exercise IAB (t(57)=2.78, p<0.01) was significantly lower than after the rest
      condition. Craving was significantly lower than the rest condition at all
      assessments post-baseline. A short bout of physical activity reduces cravings and
      AB to chocolate cues, relative to control, irrespective of BMI or abstinence
      period.

PMID- 23962401
TI  - Brief guided imagery and body scanning interventions reduce food cravings.
AB  - Elaborated Intrusion (EI) Theory proposes that cravings occur when involuntary
      thoughts about food are elaborated; a key part of elaboration is affectively
      charged imagery. Craving can be weakened by working memory tasks that block
      imagery. EI Theory predicts that cravings should also be reduced by preventing
      involuntary thoughts being elaborated in the first place. Research has found that
      imagery techniques such as body scanning and guided imagery can reduce the
      occurrence of food thoughts. This study tested the prediction that these
      techniques also reduce craving. We asked participants to abstain from food
      overnight, and then to carry out 10 min of body scanning, guided imagery, or a
      control mind wandering task. They rated their craving at 10 points during the
      task on a single item measure, and before and after the task using the Craving
      Experience Questionnaire. While craving rose during the task for the mind
      wandering group, neither the guided imagery nor body scanning group showed an
      increase. These effects were not detected by the CEQ, suggesting that they are
      only present during the competing task. As they require no devices or materials
      and are unobtrusive, brief guided imagery strategies might form useful components
      of weight loss programmes that attempt to address cravings.

PMID- 23962402
TI  - Cooking up a culinary identity for Belgium. Gastrolinguistics in two Belgian
      cookbooks (19th century).
AB  - The notion of cookbooks as socio-historic markers in a society is generally
      accepted within food studies. As both representations and prescriptions of food
      practices, perceived habits and attitudes towards food, they represent a certain
      identity for their readers. This paper investigates the nature of the identity
      that Belgian cookbooks constructed through their rhetoric. An important part of
      this study is to explore how and to what extent explicit reference to Belgium was
      made. To this end recipe titles/labels and recipe comments used in two leading
      bourgeois cookbooks from nineteenth-century Belgium were subjected to a
      quantitative and qualitative content analysis. The analysis showed that clear
      attention was paid to national culinary preferences. In terms of a domestic
      culinary corpus, it became apparent that both the Dutch and French editions of
      these cookbooks promoted dishes that were ascribed a Belgian origin.
      Internationality, however, was also an important building block of Belgian
      culinary identity. It was part of the desire of Belgian bourgeoisie to connect
      with an international elite. It fit into the 'search for sophistication', which
      was also expressed through the high representation of the more costly meats and
      sweet dishes. In addition, other references associated with bourgeois norms and
      values, such as family, convenience and frugality, were additional building
      blocks of Belgian culinary identity. Other issues such as tradition, innovation
      and health, were also matters of concerns to these Belgian cookbooks. 

PMID- 23962403
TI  - Relation of parenting styles, feeding styles and feeding practices to child
      overweight and obesity. Direct and moderated effects.
AB  - The purpose of this study was to evaluate the direct and interacting relations of
      parenting styles, feeding styles, and feeding practices to child overweight and
      obesity. Participants were 144 mothers and children under 6 years of age. Mothers
      completed questionnaires about parenting and feeding styles and feeding
      practices. Researchers weighed and measured mothers and children or obtained
      measurements from a recent health report. Feeding practices were not directly
      related to child weight status. Compared to the uninvolved feeding style,
      authoritative and authoritarian feeding style categories were linked to lower
      odds of overweight. Feeding practices interacted with authoritative and
      authoritarian parenting styles to predict obesity: (1) healthful modeling was
      associated with 61% (OR = 0.39) reduced odds of obesity in children of
      authoritative mothers but with 55% (OR = 1.55) increased odds in children of non
      authoritative mothers and (2) covert control was linked to 156% (OR = 2.56)
      increased odds of obesity in children of authoritarian mothers but with 51% (OR =
      0.49) decreased odds in children of non-authoritarian mothers. Healthful modeling
      interacted with feeding style demandingness to predict overweight and with
      responsiveness to predict obesity. Findings suggest the need for research and
      interventions on mechanisms mediating between feeding practices and obesity in
      families characterized by non-authoritative parenting styles.

PMID- 23962404
TI  - Prevalence of and intention to change dietary and physical activity health risk
      behaviours.
AB  - Poor nutrition and insufficient physical activity contribute to high rates of
      obesity. Prevalence, intention to change and co-occurrence of four health risk
      behaviours (inadequate fruit and vegetables, excessive dietary fat, excessive
      sugary beverages and inadequate physical activity in comparison to public health
      recommendations) were investigated in an Australian population of working adults.
      Participants (n=105) completed sociodemographic and stage of change
      questionnaires. A subsample (n=40) were assessed twice to estimate test-retest
      repeatability. In the full sample, 73% were female, mean age was 33.8 years and
      mean BMI was 23.8 kg/m(2). Eighty-seven percent of participants consumed
      inadequate fruit and vegetables, 43% had excessive dietary fat, 42% had excessive
      sugary beverages and 29% had inadequate physical activity. The proportions
      intending to change each behaviour were 57%, 25%, 18% and 24%, respectively. Two
      thirds exhibited multiple risk behaviours and 38% intended to change multiple
      risk behaviours. Fruit and vegetables and dietary fat were the most commonly
      paired risk behaviours (39%) and the pair most intended to change (19%).
      Occurrence of multiple risk behaviours was associated with being male (OR 3.10,
      95% CI 1.06-9.03) or overweight/obese (OR 2.66, 95% CI 1.02-6.93). Targeting two
      risk behaviours, particularly fruit and vegetables and dietary fat, may be
      appropriate when designing health promotion programs in working populations.

PMID- 23962405
TI  - Augmentative transcranial direct current stimulation (tDCS) in poor responder
      depressed patients: a follow-up study.
AB  - OBJECTIVES: Transcranial direct current stimulation (tDCS) is a non-invasive
      neurostimulation technique that has received increasing interest in the area of
      mood disorders over the last several years. While acute, double-blind, sham
      controlled studies have already reported positive findings in terms of efficacy
      and safety for tDCS, follow-up data are lacking. This need prompted the present
      follow-up study, which assesses post-acute effects of tDCS (no maintenance
      stimulation was performed), in the mid-term, in a sample of major depressives.
      METHODS: After completing an acute, open trial of tDCS, 23 outpatients with
      either major depressive disorder or bipolar disorder entered a naturalistic
      follow-up (T1) with clinical evaluations at one week (T2), 1 month (T3), and 3
      months (T4). A quantitative analysis of Hamilton Depression Rating Scale (HAM-D),
      Montgomery-Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale
      (YMRS) total scores, through repeated measures analysis of variance (ANOVA) (T1
      T4) and paired t-test for comparing specific time points (T1-T2, T2-T3, and T3
      T4), was performed. In addition, a qualitative analysis on the basis of treatment
      response and remission (HAM-D) was performed. RESULTS: Even though a progressive
      reduction of follow-up completers was observed from T2 to T4 (95.6% at T2, 65.2%
      at T3, and 47.8% at T4), the antidepressant effects of acute tDCS persisted over
      3 months in almost half of the sample. Of note, no post-acute side effects
      emerged during the follow-up observation. The most frequent causes of drop-out
      from this study included major modifications in therapeutic regimen (30%) and
      poor adherence to follow-up visits (17%). CONCLUSIONS: In this mid-term, open,
      follow-up study, tDCS showed mixed results. Further controlled studies are
      urgently needed to assess its effects beyond the acute phase.

PMID- 23962406
TI  - The critical role of nurses to the successful implementation of the National
      Safety and Quality Health Service Standards.
AB  - The National Safety and Quality Health Service Standards requires health service
      compliance by 2013 and covers several areas including governance arrangements,
      partnerships with consumers and eight key clinical processes. Nurses in Australia
      comprise 62% of the hospital workforce, are the largest component and hence play
      a critical role in meeting these standards and improving the quality of patient
      care. Several of the standards are influenced by nursing interventions, which
      incorporate any direct-care treatment that the nurse performs for a patient that
      may be nurse or physician initiated. The ability for nurses to undertake these
      interventions is influenced by the hours of care available, the skill mix of the
      nursing workforce and the environment in which they practice. Taking into
      consideration the predicted nursing shortages, the challenge to successfully
      implement the National Safety and Quality Health Service Standards will be great.
      This paper examines the role of nursing in the delivery of the National
      Standards, analyses the evidence with regard to nursing-sensitive outcomes and
      discusses the implications for health service decision makers and policy. 

PMID- 23962408
TI  - Operative management of external auditory canal cholesteatoma: case series and
      literature review.
AB  - OBJECTIVES: To describe the clinical features of external auditory canal
      cholesteatoma, and to assess the outcome following bony meatoplasty with tragal
      cartilage and perichondrium graft repair. METHODS: A retrospective review was
      carried out, comprising all patients with external auditory canal who presented
      between January 2007 and December 2011. Patients underwent pre-operative
      audiometry and computed tomography imaging of the temporal bones, before
      undergoing bony meatoplasty via a postauricular incision. Pre- and post-operative
      comparisons were made of patients' otological symptoms and the otoscopic
      appearance of the external ear canal. RESULTS AND CONCLUSION: Eight patients were
      included in the analyses. The median age of patients was 46.5 years (range 14-68
      years), with a male to female ratio of 1:1. The median length of follow up was 16
      months. The most common presenting features were unilateral otalgia and purulent
      otorrhoea. All patients had relatively advanced disease at presentation, with
      erosion of the temporal bone. All patients underwent bony meatoplasty via a
      postauricular approach to eradicate the disease. Bony meatoplasty was successful
      in the definitive management of external ear canal cholesteatoma.

PMID- 23962407
TI  - The peroxisome-proliferator activated receptor-gamma agonist pioglitazone
      modulates aberrant T cell responses in systemic lupus erythematosus.
AB  - PPAR-gamma agonists can suppress autoimmune responses and renal inflammation in
      murine lupus but the mechanisms implicated in this process remain unclear. We
      tested the effect of the PPAR-gamma agonist pioglitazone in human lupus and
      control PBMCs with regard to gene regulation and various functional assays. By
      Affymetrix microarray analysis, several T cell-related pathways were
      significantly highlighted in pathway analysis in lupus PBMCs. Transcriptional
      network analysis showed IFN-gamma as an important regulatory node, with
      pioglitazone treatment inducing transcriptional repression of various genes
      implicated in T cell responses. Confirmation of these suppressive effects was
      observed specifically in purified CD4+ T cells. Pioglitazone downregulated lupus
      CD4+ T cell effector proliferation and activation, while it significantly
      increased proliferation and function of lupus T regulatory cells. We conclude
      that PPAR-gamma agonists selectively modulate CD4+ T cell function in SLE
      supporting the concept that pioglitazone and related,-agents should be explored
      as potential therapies in this disease. 

PMID- 23962409
TI  - Phylogeography sheds light on the central-marginal hypothesis in a Mediterranean
      narrow endemic plant.
AB  - BACKGROUND AND AIMS: Understanding the factors that shape variation in genetic
      diversity across the geographic ranges of species is an important challenge in
      the effort to conserve evolutionary processes sustaining biodiversity. The
      historical influences leading to a central-marginal organization of genetic
      diversity have been explored for species whose range is known to have expanded
      from refugia after glacial events. However, this question has rarely been
      addressed for Mediterranean endemic plants of azonal habitats such as rocky
      slopes or screes. In this context, this comprehensive study examined molecular
      and field data from Arenaria provincialis (Caryophyllaceae), a narrow endemic
      plant of south-eastern France. METHODS: Across the whole geographic range, an
      investigation was made of whether high levels of abundance and genetic diversity
      (estimated from amplified fragment length polymorphism markers) are centrally
      distributed, to evaluate the relevance of the central-marginal hypothesis.
      Phylogeographic patterns inferred from chloroplast DNA (cpDNA) were used,
      applying Bayesian methods to test the influence of past biogeographic events.
      Multivariate analysis combining phylogeographic and ecological data was used to
      reveal the historical and ecological distinctiveness of populations. KEY RESULTS:
      Despite the narrow distribution of A. provincialis, a high level of nucleotide
      variation is found within cpDNA loci, supporting its persistence throughout the
      Pleistocene period. The area characterized by the highest genetic diversity is
      centrally located. Structured phylogeography and Bayesian factor analysis
      supported the hypothesis that the central area of the distribution was the source
      of both westward and eastward migrations, probably during arid periods of the
      Pleistocene, and more recently was a crossroads of backward migrations. By
      contrast, the two areas located today at the range limits are younger, have
      reduced genetic diversity and are marginal in the ecological gradients.
      CONCLUSIONS: This study highlights a case of strong population distinctiveness
      within a narrow range. Phylogeography sheds light on the historical role of the
      areas centrally situated in the distribution. The current range size and
      abundance patterns are not sufficient to predict the organization of genetic
      diversity.

PMID- 23962410
TI  - A preliminary investigation into the existence of a hypervigilance subtype of
      auditory hallucination in people with psychosis.
AB  - BACKGROUND: The phenomenological heterogeneity of auditory hallucinations (AHs)
      means individual models struggle to account for all aspects of the experience.
      One alternative is that distinct subtypes of AHs exist, with each requiring their
      own unique explanatory model and tailored cognitive behavioural intervention
      strategies. AIMS: This exploratory study tested for the presence of one specific
      potential AH-subtype, hypervigilance hallucinations (HV-AHs). METHOD: Four
      specific aspects of the phenomenology of AHs (chosen on the basis of the
      predicted phenomenology of HV-AHs) were assessed using a semi-structured
      interview in 32 individual AHs taken from reports from 15 patients with
      psychosis. RESULTS: Cluster analysis (at the level of the individual AH
      experience) offered support for the existence of a distinct HV-AH subtype,
      characterized by hearing threatening, externally-located voices when attention
      was externally-focused. Other clusters identified all shared the contrasting
      properties of occurring in quiet contexts when patients' attention was internally
      focused. CONCLUSIONS: The results offered tentative support for the existence of
      an HV-AH subcategorization and justifies future research in larger samples.
      Potential implications for models of AHs are also considered.

PMID- 23962411
TI  - Health benefits in 2013: moderate premium increases in employer-sponsored plans.
AB  - Employer-sponsored health insurance premiums rose moderately in 2013, the annual
      Kaiser Family Foundation/Health Research and Educational Trust (Kaiser/HRET)
      Employer Health Benefits Survey found. In 2013 single coverage premiums rose 5
      percent to $5,884, and family coverage premiums rose 4 percent to $16,351. The
      percentage of firms offering health benefits (57 percent) was similar to that in
      2012, as was the percentage of workers at offering firms who were covered by
      their firm's health benefits (62 percent). The share of workers with a deductible
      for single coverage increased significantly from 2012, as did the share of
      workers in small firms with annual deductibles of $1,000 or more. Most firms (77
      percent), including nearly all large employers, continued to offer wellness
      programs, but relatively few used incentives to encourage employees to
      participate. More than half of large employers offering health risk appraisals to
      workers offered financial incentives for completing the appraisal.

PMID- 23962412
TI  - Victorian junior doctors' perception of their competency and training needs in
      healthcare management.
AB  - INTRODUCTION: Australian medical speciality colleges have adapted and integrated
      the CanMEDS Physician Competency Framework into their training programs. The role
      as manager is one of the competencies and is presently thought to receive little
      attention during training. The objective of our study was to investigate the
      perceptions of Australian junior doctors regarding their management skills and
      their perceived need for management education. METHODS: In November and December
      2011, 1376 junior doctors from eight Victorian metropolitan health services were
      invited via email to participate in this study. Participating junior doctors
      received a questionnaire regarding their self- perceived management skills and
      knowledge and a medical management training needs assessment. RESULTS: The
      response rate of one of the health centres was too low (6%) and therefore
      insufficient for credible conclusions to be drawn. Of the other health services,
      194 (16%) out of 1213 junior doctors responded to the survey. Overall, the junior
      doctors rated their perceived competency on a 1-5 Likert scale as moderate (mean
      3.45; s.d. 0.42). Of the 194 residents who responded, 71.3% (n=139) reported a
      need for management training. DISCUSSION: The junior doctors of Victoria,
      Australia perceived their knowledge on medical management as moderate. The
      results of this study showed that there is a perceived need among junior doctors
      for more management training. This need seems to confirm that management skills
      are thought to be valuable in medical practice. Our study also suggests that
      before the development of specific interventions, there is a need for a gap
      analysis between the perceived and actual management skills desired in medical
      residents. The attention paid to the role 'as manager' should therefore be
      embedded in training of all junior doctors.

PMID- 23962413
TI  - Detecting nested clusters of human alveolar echinococcosis.
AB  - Recent changes in the epidemiology of alveolar echinococcosis (AE) in Eurasia
      have led to increasing concerns about the risk of human AE and the need for a
      thorough evaluation of the epidemiological situation. The aim of this study was
      to explore the use of a National Register to detect complex distribution patterns
      on several scales. The data were human AE cases from the FrancEchino register,
      diagnosed in France from 1982 to 2011. We used the Kulldorff spatial scan
      analysis to detect non-random locations of cases. We proposed an exploratory
      method that was based on the successive detection of nested clusters inside each
      of the statistically significant larger clusters. This method revealed at least 4
      levels of disease clusters during the study period. The spatial variations of
      cluster location over time were also shown. We conclude that National Human AE
      registers, although not exempted from epidemiological biases, are currently the
      best way to achieve an accurate representation of human AE distribution on
      various scales. Finally, we confirm the multi-scale clustered distribution of
      human AE, and we hypothesize that our study may be a reasonable starting point
      from which to conduct additional research and explore the processes that underlie
      such distributions.

PMID- 23962414
TI  - Preliminary evidence for a sex-specific relationship between amount of cannabis
      use and neurocognitive performance in young adult cannabis users.
AB  - Accumulating evidence suggests neuropsychological deficits from cannabis use,
      with a burgeoning area of preclinical research indicating possible sex
      differences. However, few studies have examined how cannabis use may
      differentially impact neurocognition in male and female cannabis users. As such,
      we examined potential sex-differences in associations between amount of cannabis
      use (across several time frames) and neurocognitive performance among young adult
      regular cannabis users. Consistent with previous studies, more cannabis use was
      generally associated with poorer episodic memory and decision-making, but not
      other measures of inhibitory control. However, patterns of results suggested sex
      specific dissociations. In particular, more cannabis use was more consistently
      associated with poorer episodic memory performance in females than males.
      Conversely, more cannabis use was associated with poorer decision-making
      performance for males, but not females. These results provide further evidence
      for residual cannabis-associated neurocognitive deficits and suggest the
      importance of examining the impact of cannabis on neurocognition separately for
      males and females.

PMID- 23962415
TI  - Disparities in equity and access for hospitalised atherothrombotic disease.
AB  - OBJECTIVE: This study of equity and access characterises admissions for coronary,
      cerebrovascular and peripheral arterial disease by hospital type (rural, tertiary
      and non-tertiary metropolitan) in a representative Australian population.
      METHODS: We conducted a descriptive analysis using data linkage of all residents
      aged 35-84 years hospitalised in Western Australia with a primary diagnosis for
      an atherothrombotic event in 2007. We compared sociodemographic and clinical
      features by atherothrombotic territory and hospital type. RESULTS: There were
      11670 index admissions for atherothrombotic disease in 2007 of which 46% were in
      tertiary hospitals, 41% were in non-tertiary metropolitan hospitals and 13% were
      in rural hospitals. Coronary heart disease comprised 72% of admissions, followed
      by cerebrovascular disease (19%) and peripheral arterial disease (9%).
      Comparisons of socioeconomic disadvantage reveal that for those admitted to rural
      hospitals, more than one-third were in the most disadvantaged quintile, compared
      with one-fifth to any metropolitan hospital. CONCLUSIONS: Significant differences
      in demographic characteristics were evident between Western Australian tertiary
      and non-tertiary hospitals for patients hospitalised for atherothrombotic
      disease. Notably, the differences among tertiary, non-tertiary metropolitan and
      rural hospitals were related to socioeconomic disadvantage. This has implications
      for atherothrombotic healthcare provision and the generalisation of research
      findings from studies conducted exclusively in the tertiary metropolitan
      hospitals.

PMID- 23962416
TI  - Adolescent conduct problems and premature mortality: follow-up to age 65 years in
      a national birth cohort.
AB  - BACKGROUND: Severe youth antisocial behaviour has been associated with increased
      risk of premature mortality in high-risk samples for many years, and some
      evidence now points to similar effects in representative samples. We set out to
      assess the prospective association between adolescent conduct problems and
      premature mortality in a population-based sample of men and women followed to the
      age of 65 years. METHOD: A total of 4158 members of the Medical Research Council
      National Survey of Health and Development (the British 1946 birth cohort) were
      assessed for conduct problems at the ages of 13 and 15 years. Follow-up to the
      age of 65 years via the UK National Health Service Central Register provided data
      on date and cause of death. RESULTS: Dimensional measures of teacher-rated
      adolescent conduct problems were associated with increased hazards of death from
      cardiovascular disease by the age of 65 years in men [hazard ratio (HR) 1.17, 95%
      confidence interval (CI) 1.04-1.32], and of all-cause and cancer mortality by the
      age of 65 years in women (all-cause HR 1.16, 95% CI 1.07-1.25). Adjustment for
      childhood cognition and family social class did little to attenuate these risks.
      Adolescent conduct problems were not associated with increased risks of
      unnatural/substance-related deaths in men or women in this representative sample.
      CONCLUSIONS: Whereas previous studies of high-risk delinquent or offender samples
      have highlighted increased risks of unnatural and alcohol- or substance abuse
      related deaths in early adulthood, we found marked differences in mortality risk
      from other causes emerging later in the life course among women as well as men.

PMID- 23962418
TI  - Model-based iterative reconstruction for multi-detector row CT assessment of the
      Adamkiewicz artery.
AB  - PURPOSE: To determine if model-based iterative reconstruction (MBIR) can improve
      visualization of the Adamkiewicz artery on multi-detector row computed
      tomographic (CT) images compared with adaptive statistical iterative
      reconstruction (ASIR) and filtered back projection (FBP). MATERIALS AND METHODS:
      This retrospective study was approved by the institutional review board, and
      written informed consent for the CT examination was obtained. Thirty-three
      patients underwent contrast material-enhanced 64-section multi-detector row CT
      for assessment of aortic aneurysm or dissection. Helical data were reconstructed
      by using FBP, ASIR, and MBIR. The signal-to-noise ratio of the aorta and contrast
      to-noise ratio of the anterior spinal artery relative to the spinal cord were
      measured on multiplanar reformatted images. Visualization of the Adamkiewicz
      artery and its continuity with the intercostal or lumbar artery were evaluated by
      using a four-point scale. All image analyses were performed by two blinded,
      independent observers. The one-way analysis of variance and the Wilcoxon signed
      rank test were used for statistical analysis. RESULTS: MBIR showed significantly
      better signal-to-noise and contrast-to-noise ratios than did ASIR and FBP (P <
      .05 for all comparisons) with good interobserver agreement (intraclass
      correlation coefficient of 0.93 for signal-to-noise ratio and 0.75 for contrast
      to-noise ratio). The visualization score of the Adamkiewicz artery was also
      significantly better when MBIR was used (3.4 +/- 0.8 and 3.6 +/- 0.7 for
      observers A and B, respectively) than when ASIR (2.7 +/- 1.1 and 3.0 +/- 1.0,
      respectively) or FBP (2.5 +/- 1.2 and 3.1 +/- 0.9, respectively) was used.
      CONCLUSION: Use of the MBIR algorithm led to improved multi-detector row CT
      visualization of the Adamkiewicz artery when compared with the use of ASIR and
      FBP.

PMID- 23962417
TI  - Probably benign lesions at screening breast US in a population with elevated
      risk: prevalence and rate of malignancy in the ACRIN 6666 trial.
AB  - PURPOSE: To prospectively validate predefined breast ultrasonographic (US) Breast
      Imaging Reporting and Data System (BI-RADS) category 3 criteria in a multicenter
      setting in an elevated-risk population. MATERIALS AND METHODS: The American
      College of Radiology Imaging Network 6666 database was reviewed for prospectively
      defined BI-RADS category 3 lesions. Patient characteristics, lesion US features
      at initial detection, and work-up recommendations were analyzed with descriptive
      statistics. Exact 95% confidence intervals (CIs) were given, where appropriate.
      Lesion reference standard was biopsy or a minimum of 1-year follow-up. In
      addition, malignancy rate for lesions that had at least 2 years of follow-up data
      or that had biopsy data was calculated. RESULTS: Of 2662 participants, 519
      (19.5%) had 745 BI-RADS category 3 lesions (25.5% of 2916 US lesions other than
      simple cysts), with a median size of 7 mm (range, 2-135 mm). The number of new BI
      RADS category 3 lesions decreased with year 2-3 screening, but the percentage of
      new BI-RADS category 3 lesions was stable at 26.4% (506 of 1920 lesions), 23.6%
      (142 of 601 lesions), and 24.6% (97 of 395 lesions), respectively. Of 745 BI-RADS
      category 3 lesions, 124 (16.6%) were ultimately sampled for biopsy. Six
      malignancies (0.8% of BI-RADS category 3 lesions; 95% confidence interval [CI]:
      0.3%, 1.7%) occurred in five (1.0%) of 519 participants: Five malignancies were
      invasive (median size, 10 mm; size range, 2-18 mm), and one was node positive.
      When the analysis is limited to lesions with at least 2-year follow-up or biopsy,
      the malignancy rate among BI-RADS category 3 lesions is 0.9% (95% CI: 0.3%,
      2.0%). Three malignant BI-RADS category 3 lesions were sampled for biopsy because
      of a suspicious change at follow-up (two N0 lesions, one each at 6- and 12-month
      follow-up; one N1 lesion at 24-month follow-up), one was sampled for biopsy
      because of an upgrade after additional mammography (NX), one was found at
      mastectomy for another cancer (N0), and one was found at prophylactic
      contralateral mastectomy in the same patient (NX). CONCLUSION: As BI-RADS
      category 3 lesions have a low malignancy rate (0.8%; 95% CI: 0.3%, 1.7%) and only
      0.1% of the cancers had suspicious changes at 6-month follow-up and only one
      (17%; 95% CI: 0.4%, 64%) of six malignancies were node positive at detection (24
      month follow-up), a recommendation of 1-year diagnostic follow-up may be
      appropriate for BI-RADS category 3 lesions detected at screening US. Online
      supplemental material is available for this article.

PMID- 23962419
TI  - Economic evaluation: a comparison of methadone versus buprenorphine for opiate
      substitution treatment.
AB  - BACKGROUND: The cost of opiate substitution is usually considered lower in cost
      when methadone is used, as compared to that of buprenorphine, however the overall
      cost effectiveness of substitution programmes comparing the two drugs remains
      largely unknown. METHODS: We evaluated the treatment cost and effectiveness of
      methadone and buprenorphine when used in an opiate substitution programme in
      Norfolk, UK. All programme costs, estimated from the perspective of the drug
      treatment clinic, were collected on 361 opiate-dependent participants over a six
      month period. Total costs comprised medication (methadone or buprenorphine)
      costs, pharmacy supervision and dispensing costs, and drug service clinic costs.
      Effectiveness was measured in terms of (1) each programmes ability to retain
      participants in the programme for six months, and (2) the ability of the
      programme to accomplish complete abstinence from illicit opiate consumption.
      RESULTS: Overall, mean medication-only costs of methadone were lower than that of
      buprenorphine, however, pharmacy and clinic costs were lower for the
      buprenorphine programme. The covariate-adjusted mean total cost of the two
      programmes was not significantly different. Mean six-month retention rates were
      higher on the methadone programme, therefore, the methadone programme "dominates"
      the buprenorphine programme as it was slightly more effective for the same cost.
      Conversely, when ability to stop taking illicit opiates concomitant with opiate
      substitution medication was considered, the buprenorphine programme was more
      effective with an additional cost of L903 per individual who stopped illicit
      opiate use. CONCLUSIONS: The provision of buprenorphine should be considered an
      appropriate treatment if cessation of illicit opiate use, concomitant with
      programme retention is considered an important outcome.

PMID- 23962420
TI  - Attitude and risk of substance use in adolescents diagnosed with Asperger
      syndrome.
AB  - BACKGROUND: Adolescence is a stage of development with increased risk of drug
      use. Individual personality traits are among those factors that influence the
      onset of substance use in adolescence and its psychiatric comorbidity. Little
      research has been done on the comorbidity between substance abuse risk and
      Asperger syndrome, and none specifically in adolescence. The objective of this
      study is to assess the risk of drug use by adolescents with Asperger syndrome and
      compare it with that risk in control subjects. A secondary objective was to
      analyze the personality factors that may be associated with substance use in the
      same two groups. METHODS: We used three self-administered questionnaires, one for
      drug risk assessment (FRIDA) and the other two for personality trait assessment
      (MACI and SSS-V). RESULTS: Adolescents diagnosed with Asperger syndrome are at
      less risk for drug use derived from family and access to drugs factors. Subjects
      with Asperger syndrome did score higher on introversive, inhibited, doleful, and
      borderline tendency prototypes than healthy controls, and scored lower on all
      sensation-seeking traits. Being male, a diagnosis of Asperger syndrome, and
      unruly, introversive, and sensation-seeking traits were all independently
      associated with the risk of drug abuse. CONCLUSIONS: Both identified personality
      factors and other variables associated with the Asperger syndrome contribute to
      the low risk of drug abuse observed in this population. Exploring protective
      factors for drug use in these subjects may prove useful for interventions with
      adolescents at risk for consumption.

PMID- 23962422
TI  - Impact of an education intervention using email for the prevention of weight gain
      among adult workers.
AB  - OBJECTIVE: To evaluate the impact of a worksite intervention to prevent weight
      gain among adult workers. DESIGN: A controlled community trial was performed by
      dividing the workers into two groups: intervention group (IG) and control group
      (CG). The theoretical framework applied was Intervention Mapping Protocol and the
      intervention was implemented through interactive software for weight self
      monitoring. To evaluate the impact of the intervention, the differences in
      weight, BMI and waist circumference between the IG and CG were assessed before
      and 6 months after the intervention by regression models. Additionally, the
      sustainability of the intervention was evaluated at 12 months after the
      intervention. Settings Sao Paulo, Brazil. SUBJECTS: Four companies; 281 workers
      for the analysis of effectiveness and 427 for the analysis of sustainability.
      RESULTS: The intervention resulted in significant reductions in weight, BMI and
      waist circumference in the IG compared with the CG. The impact of the
      intervention on IG individuals' body weight was -0.73 kg, while the weight of CG
      individuals increased. IG individuals with adequate initial weights did not show
      significant variations, while those who were overweight demonstrated a
      significant reduction in body weight. The intervention resulted in a reduction of
      0.26 kg/m2 in BMI and 0.99 cm in waist circumference, and the sustainability
      analysis after 12 months showed a continued reduction in body weight (-0.72 kg).
      CONCLUSIONS: The behavioural intervention was effective, resulting in weight
      maintenance among participants with adequate initial weight and in significant
      reductions among those who were overweight. More research on longer-term weight
      maintenance is needed.

PMID- 23962421
TI  - The latent structure and predictors of non-medical prescription drug use and
      prescription drug use disorders: a national study.
AB  - BACKGROUND: Despite growing concerns about non-medical prescription drug use and
      prescription drug use disorders, whether vulnerability for these conditions is
      drug-specific or occurs through a shared liability and common risk factors is
      unknown. METHODS: Exploratory and confirmatory factor analysis of Wave 1 of the
      National Epidemiologic Survey on Alcohol and Related Conditions were used to
      examine the latent structure of non-medical prescription drug use and
      prescription drug use disorders. Multiple Indicators Multiple Causes (MIMIC)
      analysis was used to examine whether the effect of sociodemographic and
      psychiatric covariates occurred through the latent factor, directly on each drug
      class or both. RESULTS: A one-factor model described well the structure of both
      non-medical prescription drug use and prescription drug use disorders. Younger
      age, being White, having more intense pain or one of several psychiatric
      disorders increased the risk of non-medical prescription drug use through the
      latent factor. The same covariates, except for anxiety disorders also
      significantly increased the risk of prescription drug use disorders through the
      latent factor. Older age directly increased the risk of non-medical use of
      sedatives, and alcohol use disorders decreased the risk of non-medical
      tranquilizer use. No covariates had direct effects on the risk of any
      prescription drug use disorders beyond their effect through the latent factor.
      CONCLUSION: The risk for non-medical prescription drug use and prescription drug
      use disorders occurs through a shared liability. Treatment, prevention and policy
      approaches directed at these drugs as a group maybe more effective than those
      focused on individual classes of drugs.

PMID- 23962423
TI  - Comparison of markers of coagulation activation and thrombin generation test in
      uncomplicated pregnancies.
AB  - INTRODUCTION: Pregnancy is a well-established risk factor for venous
      thromboembolism, and is associated with a state of hypercoagulability or
      parameters of thrombin generation. Currently, there is a lack of consensual data
      on thrombin generation during pregnancy. This study aimed to find a sensitive and
      specific biological marker of coagulation activation and to identify parameters
      of thrombin generation. PATIENTS AND METHODS: The population included 101 women
      with uncomplicated pregnancies. The objective of this study was to correlate
      thrombin generation test (measured at 5pM tissue factor, 4MUM lipids and without
      thrombomodulin), with fibrinogen and markers of blood coagulation activation: D
      dimer, prothrombin fragments 1+2 (F1+2), thrombin-antithrombin complexes (TAT)
      and fibrin monomer complexes (FMC) in these women. Internal quality control was
      performed in each set of experiments. RESULTS: Fibrinogen, D-dimer, F1+2, and TAT
      concentrations increased significantly throughout pregnancy, and were correlated
      with term of pregnancy. In our study, thrombin generation seemed to increase
      early on, and then remained stable throughout normal pregnancy, in contrast with
      other markers of blood coagulation activation, excepting FMC. The latter are
      subject to large inter-individual variations, especially during second trimester.
      No correlation was demonstrated between thrombin generation parameters and other
      activation markers. CONCLUSION: While markers of coagulation activation
      significantly increased during pregnancy, thrombin generation increased only
      early on and remains stable during pregnancy. Finding a sensitive and specific
      biological marker for vascular pregnancy complications, such as FMC and thrombin
      generation levels, requires further investigation.

PMID- 23962424
TI  - Health management and patients who lack capacity: forms of guardianship in
      European health policy.
AB  - The focus of healthcare debate has in recent years shifted from doctors and
      healthcare professionals in general to patients and the principle of patient self
      determination. Patient competence therefore plays an increasingly central role in
      the legal framework of many Europeans countries. Consequently, healthcare policy
      has to address the possible repercussions of a non-systematic approach to cases
      of patient incapacity. The diverse nature of the experiences of the mentally or
      physically disadvantaged clearly raises problems for the healthcare professional.
      In this setting, we examine Italy's Law no. 6/2004 from a comparative
      perspective, in particular analysing legislation in the same area from Spain,
      France, Great Britain and the Netherlands. 

PMID- 23962425
TI  - Immune senescence: new insights into defects but continued mystery of root
      causes.

PMID- 23962426
TI  - Decrease of WNK4 ubiquitination by disease-causing mutations of KLHL3 through
      different molecular mechanisms.
AB  - Recently, we demonstrated that WNK4 is a substrate for KLHL3-Cullin3 (CUL3) E3
      ubiquitin ligase complexes and that impaired WNK4 ubiquitination is a common
      mechanism for pseudohypoaldosteronism type II (PHAII) caused by WNK4, KLHL3, and
      CUL3 mutations. Among the various KLHL3 mutations that cause PHAII, we
      demonstrated that the R528H mutation in the Kelch domain decreased the binding to
      WNK4, thereby causing less ubiquitination and increased intracellular levels of
      WNK4. However, the pathogenic mechanisms of PHAII caused by other KLHL3 mutants
      remain to be determined. In this study, we examined the pathogenic effects of
      three PHAII-causing mutations in different KLHL3 domains; the protein levels of
      these mutants significantly differed when they were transiently expressed in
      HEK293T cells. In particular, S410L expression was low even with increased
      plasmid expression. The cycloheximide chase assay revealed that an S410L mutation
      in the Kelch domain significantly decreased the intracellular stability.
      Mutations in E85A in the BTB domain and C164F in the BACK domain decreased the
      binding to CUL3, and S410L as well as R528H demonstrated less binding to WNK4. In
      vitro and in vivo assays revealed that these mutants decreased the ubiquitination
      and increased the intracellular levels of WNK4 compared with wild-type KLHL3.
      Therefore, the KLHL3 mutants causing PHAII investigated in this study exhibited
      less ability to ubiquitinate WNK4 because of KLHL3's low stability and/or
      decreased binding to CUL3 or WNK4.

PMID- 23962427
TI  - Effects of differentiation on purinergic and neurotensin-mediated calcium
      signaling in human HT-29 colon cancer cells.
AB  - Calcium signaling is a key regulator of processes important in differentiation.
      In colon cancer cells differentiation is associated with altered expression of
      specific isoforms of calcium pumps of the endoplasmic reticulum and the plasma
      membrane, suggesting that differentiation of colon cancer cells is associated
      with a major remodeling of calcium homeostasis. Purinergic and neurotensin
      receptor activation are known regulators of cytosolic free Ca(2+) levels in colon
      cancer cells. This study aimed to assess changes in cytosolic free Ca(2+) levels
      in response to ATP and neurotensin with differentiation induced by sodium
      butyrate or culturing post-confluence. Parameters assessed included peak
      cytosolic free Ca(2+) level after activation; time to reach peak cytosolic free
      Ca(2+) and the EC50 of dose response curves. Our results demonstrate that
      differentiation of HT-29 colon cancer cells is associated with a remodeling of
      both ATP and neurotensin mediated Ca(2+) signaling. Neurotensin-mediated calcium
      signaling appeared more sensitive to differentiation than ATP-mediated Ca(2+)
      signaling.

PMID- 23962428
TI  - Downregulation of microRNA-214 and overexpression of FGFR-1 contribute to
      hepatocellular carcinoma metastasis.
AB  - miR-214 is one of the most significantly downregulated microRNAs (miRNAs) in
      hepatocellular carcinoma (HCC). Fibroblast growth factor receptor 1 (FGFR-1) is a
      miR-214 target gene implicated in the progression of HCC. However, the roles of
      miR-214 and FGFR-1 in HCC are not fully understood. Here, we analyzed the
      expression of miR-214 and FGFR-1 in 65 cases of HCC and paired non-neoplastic
      tissue specimens using real-time PCR and Western blot (WB), respectively. Our
      data indicated that miR-214 was downregulated and FGFR-1 was overexpressed in HCC
      compared to the paired non-neoplastic tissues. The low miR-214 expression was
      correlated with portal vein invasion (p=0.016) and early recurrence (p=0.045) in
      HCC patients. Moreover, the low miR-214 expression was correlated with high
      positive rate of FGFR-1 in HCC cases (p=0.020). Our data further demonstrated
      that miR-214 overexpression in SK-HEP1 and HepG2 cells downregulated FGFR-1
      expression and inhibited liver cancer cell invasion. The Luciferase assay results
      further demonstrated the targeted regulation of FGFR-1 by miR-214. In conclusion,
      our data indicate that the downregulation of miR-214 in HCC and the upregulation
      of its target gene FGFR-1 is associated with HCC progression. Therefore, miR-214
      and FGFR-1 are potential prognostic markers and therapeutic targets in HCC.

PMID- 23962429
TI  - PTPRT regulates the interaction of Syntaxin-binding protein 1 with Syntaxin 1
      through dephosphorylation of specific tyrosine residue.
AB  - PTPRT (protein tyrosine phosphatase receptor T), a brain-specific tyrosine
      phosphatase, has been found to regulate synaptic formation and development of
      hippocampal neurons, but its regulation mechanism is not yet fully understood.
      Here, Syntaxin-binding protein 1, a key component of synaptic vesicle fusion
      machinery, was identified as a possible interaction partner and an endogenous
      substrate of PTPRT. PTPRT interacted with Syntaxin-binding protein 1 in rat
      synaptosome, and co-localized with Syntaxin-binding protein 1 in cultured
      hippocampal neurons. PTPRT dephosphorylated tyrosine 145 located around the
      linker between domain 1 and 2 of Syntaxin-binding protein 1. Syntaxin-binding
      protein 1 directly binds to Syntaxin 1, a t-SNARE (soluble N-ethylmaleimide
      sensitive factor attachment protein receptor) protein, and plays a role as
      catalysts of SNARE complex formation. Syntaxin-binding protein 1 mutant mimicking
      non-phosphorylation (Y145F) enhanced the interaction with Syntaxin 1 compared to
      wild type, and therefore, dephosphorylation of Syntaxin-binding protein 1
      appeared to be important for SNARE-complex formation. In conclusion, PTPRT could
      regulate the interaction of Syntaxin-binding protein 1 with Syntaxin 1, and as a
      result, the synaptic vesicle fusion appeared to be controlled through
      dephosphorylation of Syntaxin-binding protein 1.

PMID- 23962430
TI  - Emotional and behavioral functioning in children with bladder exstrophy
      epispadias complex: a developmental perspective.
AB  - OBJECTIVE: To evaluate the emotional and behavioral functioning of children with
      bladder exstrophy-epispadias complex (BEEC), taking into account developmental
      and gender considerations. This study also sought to overcome methodological
      limitations of previous studies evaluating psychological well-being of children
      with BEEC. METHODS: Eighty-six children were consecutively evaluated using the
      parent report version of the Behavior Assessment System for Children during
      visits to a multidisciplinary urology clinic. RESULTS: Results indicated
      normative emotional and behavioral functioning across the sample. However, there
      was a significant effect of age, such that older children consistently had worse
      internalizing symptoms and adaptive functioning. Males tended to have more
      externalizing problems as they aged, and also tended to have lower levels of
      adaptive functioning but this was independent of age. The level of psychological
      impairment was unrelated to the specific type of BEEC, and was also unrelated to
      whether or not the patient had undergone continence surgery. CONCLUSION: Children
      with BEEC have a greater likelihood of experiencing a wide range of emotional and
      behavioral problems as they reach adolescence. These findings point to the need
      to prevent potential psychological distress by intervening with these children
      before they become clinically impaired.

PMID- 23962431
TI  - Objective use of testosterone reveals androgen insensitivity in patients with
      proximal hypospadias.
AB  - OBJECTIVE: We report preoperative testosterone stimulation based on glans width
      measurements in patients with midshaft and proximal hypospadias, revealing
      androgen resistance in those with proximal hypospadias. METHODS: Patients had
      maximum glans width measured preoperatively. Those <14 mm initially received 2
      mg/kg testosterone cypionate intramuscularly for two to three doses, with the aim
      of increasing glans width >= 15 mm. Not all patients achieved targeted growth,
      and some were subsequently treated with escalating doses of testosterone.
      RESULTS: 5/15 midshaft patients had two to three doses of 2 mg/kg testosterone,
      with all increasing glans width to >= 15 mm. 29/47 proximal patients had
      testosterone, with 13 (57%) not reaching desired glans width. Six of these and
      another six patients had escalating doses from 4 to 32 mg/kg testosterone, with
      11 then achieving targeted glans width. Relative androgen resistance was found in
      19/29 (66%) proximal cases, including all treated patients with perineal
      hypospadias. CONCLUSIONS: 39/62 (63%) patients met objective criteria for
      preoperative testosterone stimulation based on glans width <14 mm, which is less
      than the average normal newborn glans diameter. Evidence of relative androgen
      resistance was found in 19 (49%), all with proximal hypospadias.

PMID- 23962432
TI  - Male European eels are highly efficient long distance swimmers: effects of
      endurance swimming on maturation.
AB  - European eels (Anguilla anguilla) migrate ~6000km towards their spawning area in
      the Sargasso Sea. Based on the recent discovery that males swim even more
      efficiently than females, it was predicted that males also would be able to swim
      ~6000km within six months. Additionally, eels do not mature naturally in
      captivity due to strong neural inhibition. Earlier, it was hypothesized that
      swimming exercise is a natural trigger to induce sexual maturation and may even
      result in full maturation. In the present study two groups of farmed male silver
      eels were subjected to either endurance swimming or resting for up to 6months. It
      was found that male eels were able to swim continuously for a total distance of
      6670km within 6months. The body weight decrease in swimming and resting males
      after 6months was similar (<30g) underlining the extreme low energy cost of
      swimming. In contrast to our expectation long-term swimming did not induce sexual
      maturation in farmed silver eels, suggesting that swimming alone is not
      sufficient as a trigger for sexual maturation. In conclusion, male eels are
      efficient long distance swimmers and likely able to cover the distance to the
      Sargasso Sea within the expected time span of 6months. 

PMID- 23962433
TI  - Jumpstarting post-conflict strategic water resources protection from a changing
      global perspective: gaps and prospects in Afghanistan.
AB  - Notwithstanding ambiguities, long-term economic resurgence in Afghanistan amidst
      water insecurity exacerbated by climate change decisively requires a water
      protection strategy that will complement a multitude of agroindustrial and
      socioeconomic activities in an environmentally sustainable and climate resilient
      manner. In this paper, we begin with a perspective on institutions, legislation,
      and key issues in the water sector of Afghanistan. We then embark on linking the
      integrated water resources management (IWRM) and strategic environmental
      assessment (SEA) approaches as a novel framework for strategic water management
      and subsequently propose a strategy for post-conflict water protection based on
      the coalesced IWRM and SEA. Context relevant good practices worldwide are
      presented to provide empirical evidence for this approach whereas perceived
      opportunities and vulnerabilities in the Afghan context are discussed.
      Examination of post-conflict water sector initiatives in Afghanistan reveals the
      critical role of foreign assistance in both water infrastructure rehabilitation
      and modernization of the institutional aspect of water management. The
      introduction of IWRM as the basis for a progressive water sector strategy has
      been seen as a major milestone which is detrimentally matched by substantial
      deficiency in national capacity for implementation. Concurrently, the role of
      extra-national actors in relevant policy interventions has been considered
      catalytic despite criticisms of proposed regulations as being anachronistic to
      field realities. Therefore the view is maintained to practicable policies by
      accelerating policy learning in the country's water and environment sectors to
      encourage homegrown water strategy innovations. Demonstratively, mainstreaming
      IWRM-SEA coalescence will bridge institutional gaps for better feedback between
      local and national water stakeholders, providing a venue for improved delivery of
      water services to sustain post-conflict socioeconomic recovery and promote
      environmental stewardship. 

PMID- 23962434
TI  - A pilot neighborhood study towards establishing a benchmark for reducing
      electromagnetic field levels within single family residential dwellings.
AB  - Electromagnetic fields (EMF) permeate the built environment in different forms
      and come from a number of sources including electrical wiring and devices,
      wireless communication, 'energy-efficient' lighting, and appliances. It can be
      present in the indoor environment directly from indoor sources, or can be
      transmitted through building materials from outside sources. Scientists have
      identified it as an indoor environmental pollutant or toxin that has ubiquitously
      plagued developed nations causing a variety of adverse health effects such as
      sick-building syndrome symptoms, asthma, diabetes, multiple sclerosis, leukemia,
      electro-hypersensitivity (EHS), behavior disorders, and more. There is currently
      no international consensus on guidelines and exposure limits. This paper presents
      the results of 29 EMF field audits in single family residential dwellings located
      within an urban neighborhood in Toronto (Canada). The following EMF spectra were
      evaluated: radio frequency, power frequency electric fields, power frequency
      magnetic fields and high frequency voltage transients. The field audits were
      conducted in order to provide initial baseline statistics to be used in future
      studies and in order to be compared to a low-cost EMF reduction design
      incorporated within the Renovation2050 research house - located within the test
      neighborhood. The results show the low-cost reduction strategy to be effective,
      on average reducing exposure by 80% for high-intensity EMF metrics. Research of
      this nature has not been conducted with relation to the built environment and can
      be used to spark an industry movement to design for low-exposure to EMF in a
      residential context. 

PMID- 23962435
TI  - Biological early warning system based on the responses of aquatic organisms to
      disturbances: a review.
AB  - Aquatic ecosystems are subject to a number of anthropogenic disturbances,
      including environmental toxicants. The efficient monitoring of water resources is
      fundamental for effective management of water quality and aquatic ecosystems.
      Spot sampling and continuous water quality monitoring based on physicochemical
      factors are conducted to assess water quality. However, not all contaminants or
      synergistic and antagonistic toxic effects can be determined by solely analyzing
      the physicochemical factors. Thus, various biotests have been developed using
      long-term and automatic observation studies based on the ability of the aquatic
      organisms to continuously sense a wide range of pollutants. In addition, a
      biological early warning system (BEWS) has been developed based on the response
      behaviors of organisms to continuously detect a wide range of pollutants for
      effective water quality monitoring and management. However, large amounts of data
      exhibiting non-linearity and individual behavioral variation are continuously
      accumulated over long-term and continuous behavioral monitoring studies. Thus,
      appropriate mathematical and computational data analyses are necessary to manage
      and interpret such large datasets. Here, we review the development and
      application of BEWS by using various groups of organisms and the computational
      methods used to process the behavioral monitoring data. 

PMID- 23962436
TI  - The microbial communities and potential greenhouse gas production in boreal acid
      sulphate, non-acid sulphate, and reedy sulphidic soils.
AB  - Acid sulphate (AS) soils along the Baltic coasts contain significant amounts of
      organic carbon and nitrogen in their subsoils. The abundance, composition, and
      activity of microbial communities throughout the AS soil profile were analysed.
      The data from a drained AS soil were compared with those from a drained non-AS
      soil and a pristine wetland soil from the same region. Moreover, the potential
      production of methane, carbon dioxide, and nitrous oxide from the soils was
      determined under laboratory conditions. Direct microscopic counting, glucose
      induced respiration (GIR), whole cell hybridisation, and extended phospholipid
      fatty acid (PLFA) analysis confirmed the presence of abundant microbial
      communities in the topsoil and also in the deepest Cg2 horizon of the AS soil.
      The patterns of microbial counts, biomass and activity in the profile of the AS
      soil and partly also in the non-AS soil therefore differed from the general
      tendency of gradual decreases in soil profiles. High respiration in the deepest
      Cg2 horizon of the AS soil (5.66 MUg Cg(-1)h(-1), as compared to 2.71 MUg Cg(
      1)h(-1) in a top Ap horizon) is unusual but reasonable given the large amount of
      organic carbon in this horizon. Nitrous oxide production peaked in the BCgc
      horizon of the AS and in the BC horizon of the non-AS soil, but the peak value
      was ten-fold higher in the AS soil than in the non-AS soil (82.3 vs. 8.6 ng Ng(
      1)d(-1)). The data suggest that boreal AS soils on the Baltic coast contain high
      microbial abundance and activity. This, together with the abundant carbon and
      total and mineral nitrogen in the deep layers of AS soils, may result in
      substantial gas production. Consequently, high GHG emissions could occur, for
      example, when the generally high water table is lowered because of arable
      farming.

PMID- 23962437
TI  - New players in the neurovascular unit: insights from experimental and clinical
      epilepsy.
AB  - The conventional notion that neurons are exclusively responsible for brain
      signaling is increasingly challenged by the idea that brain function in fact
      depends on a complex interplay between neurons, glial cells, vascular
      endothelium, and immune-related blood cells. Recent data demonstrates that
      neuronal activity is profoundly affected by an entire cellular and extracellular
      'orchestra', the so-called neurovascular unit (NVU). Among the 'musical
      instruments' of this orchestra, there may be molecules long-known in biomedicine
      as important mediators of inflammatory and immune responses in the organism, as
      well as non-neuronal cells, e.g., leukocytes. We here review recent evidence on
      the structure and function of the NVU, both in the healthy brain and in
      pathological conditions, such as the abnormal NVU activation observed in
      epilepsy. We will argue that a better understanding of NVU function will require
      the addition of new players to the 'orchestra'. 

PMID- 23962438
TI  - Modified cisplatin-based transcatheter arterial chemoembolization for large
      hepatocellular carcinoma: multivariate analysis of predictive factors for tumor
      response and survival in a 163-patient cohort.
AB  - PURPOSE: To evaluate the safety and efficacy of modified cisplatin-based
      transcatheter arterial chemoembolization for inoperable hepatocellular carcinomas
      (HCCs) larger than 5 cm in diameter, and the factors associated with tumor
      response and survival. MATERIALS AND METHODS: From January 2007 to November 2009,
      163 patients who underwent modified cisplatin-based chemoembolization for
      inoperable large HCCs were evaluated. Predominant tumors were as large as 25 cm
      (median, 8.6 cm). Seventy-nine patients had a solitary tumor, and 84 had two or
      more tumors. Tumor response was evaluated per modified Response Evaluation
      Criteria In Solid Tumors. RESULTS: After chemoembolization, 65% of patients
      showed a tumor response. On multivariate analysis, tumor size (P < .001) and
      portal vein (PV) invasion (P = .017) were significant factors for tumor response.
      After chemoembolization, 97% of patients (56 of 58) with PV invasion received
      additional radiation therapy for PV tumor thrombosis. Median survival time was
      15.8 months. On multivariate analysis, Child-Pugh class (P = .001), surgical
      resection (P = .003) or radiofrequency (RF) ablation (P = .018) after
      chemoembolization, and tumor response (P = .002) were significant factors for
      patient survival after chemoembolization. Major complications (N = 5) included
      acute renal failure (n = 3), cholecystitis with hepatic abscess (n = 1), and
      intractable pleural effusion (n = 1). CONCLUSIONS: Transcatheter arterial
      chemoembolization is safe and effective for large HCCs. Tumor size and PV
      invasion are significant predictors of tumor response and, Child-Pugh class A
      disease, surgical resection after chemoembolization, RF ablation after
      chemoembolization, and tumor response are good prognostic factors for survival.

PMID- 23962439
TI  - Prospective evaluation of optical coherence tomography in lower limb arteries
      compared with intravascular ultrasound.
AB  - PURPOSE: To compare in a prospective noninferiority study optical coherence
      tomography (OCT) and intravascular ultrasound (IVUS) in popliteal and
      infrapopliteal vessels. MATERIALS AND METHODS: OCT and IVUS images of 112
      popliteal and infrapopliteal arterial segments were prospectively obtained from
      16 patients with peripheral arterial occlusive disease. Three observers evaluated
      the corresponding OCT and IVUS images for image quality, artifact frequency,
      discriminability of vessel wall layers, and plaque composition. Measurements of
      the lumen, vessel, and plaque areas were compared for both modalities. RESULTS:
      The intrareader and interreader reproducibility of plaque tissue discrimination
      (0.88 vs 0.75), overall image quality, and vessel wall layer discriminability
      were significantly higher for OCT (all P < .001). Artifact frequency was higher
      in OCT, constraining the imaging of the tibioperoneal trunk. The results of
      measurements of the lumen and vessel area were comparable for both modalities
      (correlation > 0.9, P < .001). Plaque area measurements differed (correlation
      0.8, P < .01) because OCT underestimated it. The OCT procedure caused vessel
      spasms in two patients. CONCLUSIONS: OCT imaging of infrapopliteal arteries is
      feasible and safe and provides high image quality. It enables an accurate
      assessment of vessel lumen, wall, and plaque. Compared with IVUS, OCT images
      provide excellent image quality and superior visualization of vessel wall layers
      and different plaque components. The penetration depth of OCT restricts its use
      to suitable vessel regions.

PMID- 23962440
TI  - Treatment of depression in diagnosed diabetes: common cause or detection bias?
AB  - BACKGROUND: This study examined two competing hypotheses concerning the
      association between diabetes and treatment for depression: (1) the
      detection/ascertainment bias hypothesis suggesting that those with diabetes are
      more likely to be diagnosed with and treated for depression because of increased
      medical attention and (2) a hypothesis assuming that diabetes and depression
      share common underlying pathophysiological pathways. METHOD: The study population
      included all persons aged 35-65 years in Finland with any record of type 2
      diabetes in the national health and population registers from 1999 to 2002 and
      for whom register-based data on depression treatment (antidepressant medication
      use and hospitalizations for depression) were available at least 2 years before
      and after the diagnosis of diabetes (n = 18,217). Sociodemographic data were
      individually linked to the study population. Associations between diabetes
      diagnosis and time and indicators of depression care were assessed with
      population-averaged multilevel logistic models. RESULTS: Within the year
      following diagnosis diabetes, there was a 5% increase in antidepressant
      medication use but not in hospitalization for depression. The longitudinal change
      in antidepressant use over time was less steep after the diabetes diagnosis, and
      hospitalization risk decreased after the diagnosis. These associations between
      diabetes diagnosis and depression treatment were not modified by the
      participant's socio-economic position (SEP). CONCLUSIONS: These findings support
      the common cause hypothesis that treatment for diabetes is beneficial to the
      prevention of depression rather than the detection/ascertainment hypothesis that
      individuals with diabetes have higher rates of depression because they receive
      more medical attention in general.

PMID- 23962441
TI  - Public-private interactions on health in South Africa: opportunities for scaling
      up.
AB  - South Africa has long recognized partnerships between the public and private
      sectors as a policy objective in health, but experience is still limited and
      poorly documented. The objectives of this article are to understand the factors
      that increase the likelihood of success of public-private interactions in South
      Africa, and identify and discuss opportunities for them to be scaled up. There is
      a strong legislative framework and a number of guidelines and tools that have
      been developed by the Treasury for managing partnerships. The review of
      literature confirmed the need for the state to have effective regulations in
      order to oversee quality and standards and to provide stewardship and oversight.
      The public sector requires sufficient capacity not only to manage relationships
      with the private sector but also to enable innovation and experimentation.
      Evaluation is an integral part of all interactions not only to learn from
      successes but also to identify any perverse incentives that may lead to
      unintended consequences. Four case studies show that the private for-profit
      sector is already engaged in a number of projects that are closely aligned to
      current health system reform priorities. Factors that increase the likelihood of
      interactions being successful include: increasing the government's capacity to
      manage public-private relationships; choosing public-private interactions that
      are strategically important to national goals; building a knowledge base on what
      works, where and why; moving from pilots to large scale initiatives; harnessing
      the contracting expertise in private providers; and encouraging innovation and
      learning. 

PMID- 23962442
TI  - Regulation of intraocular pressure in mice: structural analysis of dopaminergic
      and serotonergic systems in response to cabergoline.
AB  - Elevated intraocular pressure (IOP) is the main recognized risk factor of
      glaucoma. To investigate the contribution of dopaminergic and serotonergic
      systems in IOP regulation, we used cabergoline, a mixed dopamine and serotonin
      agonist, in C57BL/6J WT and dopamine D3 receptor knock-out (D3R-/-) mice with
      normal eye pressure or steroid-induced ocular hypertension. Furthermore, we
      studied the structural basis of the cabergoline-mediated activation of the
      dopaminergic and serotonergic systems by molecular modeling. Topical application
      of cabergoline, significantly decreased, in a dose-dependent manner, the
      intraocular pressure in WT mice, both in an ocular normotensive group (-9, -5 and
      -2 mmHg with 5%, 1%, and 0.1%, respectively) and an ocular hypertensive group,
      with a prolonged effect in this latter group. No change of intraocular pressure
      was observed after topical application of cabergoline in D3R-/- mice. We modeled
      and optimized, with molecular dynamics, structures of hD3, h5HT(1A) and h5HT(2A
      C) receptors; thereafter we carried out molecular docking of cabergoline. Docking
      revealed that binding of cabergoline into D3 and 5HT(1A) receptors is associated
      with a better desolvation energy in comparison to 5HT(2A-C) binding. In
      conclusion, the present study support the hypothesis that dopaminergic system is
      pivotal to regulate IOP and that D3R represents an intriguing target in the
      treatment of glaucoma. Furthermore, the structure-based computational approach
      adopted in this study is able to build and refine structure models of homologous
      dopaminergic and serotonergic receptors that may be of interest for structure
      based drug discovery of ligands, with dopaminergic selectivity or with multi
      pharmacological profile, potentially useful to treat optic neuropathies.

PMID- 23962443
TI  - Sophoraflavanone G induces apoptosis of human cancer cells by targeting upstream
      signals of STATs.
AB  - Aberrantly activated signal transducer and activator of transcription (STAT)
      proteins are implicated with human cancers and represent essential roles for
      cancer cell survival and proliferation. Therefore, the development of small
      molecule inhibitors of STAT signaling bearing pharmacological activity has
      therapeutic potential for the treatment of human cancers. In this study, we
      identified sophoraflavanone G as a novel small-molecule inhibitor of STAT
      signaling in human cancer cells. Sophoraflavanone G inhibited tyrosine
      phosphorylation of STAT proteins in Hodgkin's lymphoma and tyrosine
      phosphorylation of STAT3 in solid cancer cells by inhibiting phosphorylation of
      the Janus kinase (JAK) proteins, Src family tyrosine kinases, such as Lyn and
      Src, Akt, and ERK1/2. In addition, sophoraflavanone G inhibited STAT5
      phosphorylation in murine-bone-marrow-derived pro-B cells transfected with
      translocated Ets Leukemia (TEL)-JAKs and cytokine-induced rat pre-T lymphoma
      cells, as well as STAT5b reporter activity in TEL-JAKs and STAT5b reporter
      systems. Sophoraflavanone G also inhibited nuclear factor-kappaB (NF-kappaB)
      signaling in multiple myeloma cells. Furthermore, sophoraflavanone G inhibited
      cancer cell proliferation and induced apoptosis by regulating the expression of
      apoptotic and anti-apoptotic proteins. Our data suggest that sophoraflavanone G
      is a novel small-molecule inhibitor of STAT signaling by targeting upstream
      signals of STATs that may have therapeutic potential for cancers caused by
      persistently activated STAT proteins. 

PMID- 23962444
TI  - The nuclear receptors pregnane X receptor and constitutive androstane receptor
      contribute to the impact of fipronil on hepatic gene expression linked to thyroid
      hormone metabolism.
AB  - Fipronil is described as a thyroid disruptor in rat. Based on the hypothesis that
      this results from a perturbation of hepatic thyroid hormone metabolism, our goal
      was to investigate the pathways involved in fipronil-induced liver gene
      expression regulations. First, we performed a microarray screening in the liver
      of rats treated with fipronil or vehicle. Fipronil treatment led to the
      upregulation of several genes involved in the metabolism of xenobiotics,
      including the cytochrome P450 Cyp2b1, Cyp2b2 and Cyp3a1, the carboxylesterases
      Ces2 and Ces6, the phase II enzymes Ugt1a1, Sult1b1 and Gsta2, and the membrane
      transporters Abcc2, Abcc3, Abcg5, Abcg8, Slco1a1 and Slco1a4. Based on a large
      overlap with the target genes of constitutive androstane receptor (CAR) and
      pregnane X receptor (PXR), we postulated that these two nuclear receptors are
      involved in mediating the effects of fipronil on liver gene expression in
      rodents. We controlled that liver gene expression changes induced by fipronil
      were generally reproduced in mice, and then studied the effects of fipronil in
      wild-type, CAR- and PXR-deficient mice. For most of the genes studied, the gene
      expression modulations were abolished in the liver of PXR-deficient mice and were
      reduced in the liver of CAR-deficient mice. However, CAR and PXR activation in
      mouse liver was not associated with a marked increase of thyroid hormone
      clearance, as observed in rat. Nevertheless, our data clearly indicate that PXR
      and CAR are key modulators of the hepatic gene expression profile following
      fipronil treatment which, in rats, may contribute to increase thyroid hormone
      clearance. 

PMID- 23962446
TI  - Role of glycosylation in the anticancer activity of antibacterial peptides
      against breast cancer cells.
AB  - Antibacterial peptides (ABPs) with cancer-selective toxicity have received much
      more attention as alternative chemotherapeutic agents in recent years. However,
      the basis of their anticancer activity remains unclear. The modification of cell
      surface glycosylation is a characteristic of cancer cells. The present study
      investigated the effect of glycosylation, in particular sialic acid, on the
      anticancer activity of ABPs. We showed that aurein 1.2, buforin IIb and BMAP-28m
      exhibited selective cytotoxicity toward MX-1 and MCF-7 breast cancer cells. The
      binding activity, cytotoxicity and apoptotic activity of ABPs were enhanced by
      the presence of O-, N-glycoproteins, gangliosides and sialic acid on the surface
      of breast cancer cells. Among N-, O-glycoproteins and ganglioside, O
      glycoproteins almost had the strongest effect on the binding and cytotoxicity of
      the three peptides. Further, up-regulation of hST6Gal1 in CHO-K1 cells enhanced
      the susceptibility of cells to these peptides. Finally, the growth of MX-1
      xenograft tumors in mice was significantly suppressed by buforin IIb treatment,
      which was associated with induction of apoptosis and inhibition of
      vascularization. These data demonstrate that the three peptides bind to breast
      cancer cells via an interaction with surface O-, N-glycoproteins and
      gangliosides. Sialic acids act as key glycan binding sites for cationic ABP
      binding to glycoproteins and gangliosides. Therefore, glycosylation in breast
      cancer cells plays an important role in the anticancer activity of ABPs, which
      may partly explain their cancer-selective toxicity. Anticancer ABPs with cancer
      selective cytotoxicity will be promising candidates for anticancer therapy in the
      future. 

PMID- 23962447
TI  - Chikungunya and dengue autochthonous cases in Europe, 2007-2012.
AB  - A large number of autochthonous cases of dengue fever (2237) and chikungunya
      fever (231) occurred in Europe (Italy, France, Croatia, Madeira) during the
      period covered by our analysis (2007-2012). In all dengue outbreaks, the
      circulating strain, identified by means of molecular analysis, was the DENV-1
      strain. Dengue and chikungunya are infectious diseases that often result in
      hospitalizations and are associated with high public health costs. The dengue
      epidemic on the island of Madeira resulted in 122 hospitalizations. Only one
      death (from chikungunya) occurred but long-term sequelae were described after the
      chikungunya outbreak in Emilia-Romagna, Italy. Vector control is key to reducing
      the impact of these diseases. During the chikungunya outbreak in Italy and the
      dengue outbreak in Madeira, appropriate measures for the control of mosquitoes
      (Aedes aegypti and Aedes albopictus) were effectively implemented. The
      effectiveness of these measures (reducing the number of breeding sites,
      application of pesticides and insecticides, public health education) was shown in
      the context of these real-life outbreaks. All the pre-requisites for
      autochthonous transmission of both dengue virus and chikungunya virus (vectors,
      viremic returned travellers, climatic conditions) are present in Europe. Constant
      surveillance is imperative. 

PMID- 23962448
TI  - Microbial fuel cell (MFC) for bioelectricity generation from organic wastes.
AB  - Microbial fuel cells (MFCs) have gained a lot of attention recently as a mode of
      converting organic matter into electricity. In this study, a compost-based
      microbial fuel cell that generates bioelectricity by biodegradation of organic
      matter is developed. Grass cuttings, along with leaf mold, rice bran, oil cake
      (from mustard plants) and chicken droppings (waste from chickens) were used as
      organic waste. The electric properties of the MFC under anaerobic fermentation
      condition were investigated along with the influence of different types of
      membranes, the mixing of fly ash, and different types of electrode materials. It
      is observed that the maximum voltage was increased by mixing fly ash. Cellophane
      showed the highest value of voltage (around 350mV). Bamboo charcoal is good for
      anode material; however carbon fiber is better for the cathode material in terms
      of optimization of power generated. This developed MFC is a simple cell to
      generate electricity from organic waste. 

PMID- 23962445
TI  - Human ABCB1 (P-glycoprotein) and ABCG2 mediate resistance to BI 2536, a potent
      and selective inhibitor of Polo-like kinase 1.
AB  - The overexpression of the serine/threonine specific Polo-like kinase 1 (Plk1) has
      been detected in various types of cancer, and thus has fast become an attractive
      therapeutic target for cancer therapy. BI 2536 is the first selective inhibitor
      of Plk1 that inhibits cancer cell proliferation by promoting G2/M cell cycle
      arrest at nanomolar concentrations. Unfortunately, alike most chemotherapeutic
      agents, the development of acquired resistance to BI 2536 is prone to present a
      significant therapeutic challenge. One of the most common mechanisms for acquired
      resistance in cancer chemotherapy is associated with the overexpression of ATP
      binding cassette (ABC) transporters ABCB1, ABCC1 and ABCG2. Here, we discovered
      that overexpressing of either ABCB1 or ABCG2 is a novel mechanism of acquired
      resistance to BI 2536 in human cancer cells. Moreover, BI 2536 stimulates the
      ATPase activity of both ABCB1 and ABCG2 in a concentration-dependent manner, and
      inhibits the drug substrate transport mediated by these transporters. More
      significantly, the reduced chemosensitivity and BI 2536-mediated G2/M cell cycle
      arrest in cancer cells overexpressing either ABCB1 or ABCG2 can be significantly
      restored in the presence of selective inhibitor or other chemotherapeutic agents
      that also interact with ABCB1 and ABCG2, such as tyrosine kinase inhibitors
      nilotinib and lapatinib. Taken together, our findings indicate that in order to
      circumvent ABCB1 or ABCG2-mediated acquired resistance to BI 2536, a combined
      regimen of BI 2536 and inhibitors or clinically active drugs that potently
      inhibit the function of ABC drug transporters, should be considered as a
      potential treatment strategy in the clinic. 

PMID- 23962449
TI  - Economic analysis of a randomized phase III trial of gemcitabine plus vinorelbine
      compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for
      advanced non-small-cell lung cancer (Italian GEMVIN3/NCIC CTG BR14 trial).
AB  - BACKGROUND/OBJECTIVE: Non-platinum-based chemotherapy is a potential alternative
      to platinum doublet therapy for advanced non-small cell lung cancer in selected
      patients. We determined the cost-effectiveness of gemcitabine/vinorelbine
      (GEMVIN), versus cisplatin/gemcitabine (PG) or cisplatin/vinorelbine (PV), from a
      government payer perspective. METHODS: Results from a randomized trial of GEMVIN
      versus PG or PV demonstrated no significant difference in global quality of life
      (primary endpoint) or overall survival between regimens, but superior progression
      free survival for platinum-based regimens. A cost analysis was conducted using
      direct medical costs of treatment, grade 3 or 4 toxicity management, and
      investigations for the mean number of cycles per study arm. Costs were calculated
      using Canadian dollars in 2005, and then in 2013 after drug patent expiry.
      RESULTS: In 2005, GEMVIN was the most expensive regimen ($6868), and PV the least
      expensive ($4650), with an incremental cost of GEMVIN over PV of $2218.
      Diagnostic and administration costs did not differ significantly among regimens;
      GEMVIN had the lowest toxicity costs. The principal cost driver in 2005 was the
      cost of chemotherapy. In 2013, toxicity and administration costs emerged as major
      drivers; GEMVIN was less costly than PV and PG, (cost savings of $413 over PV).
      CONCLUSION: Despite similar outcomes, GEMVIN was more expensive than PV or PG in
      2005 because of higher chemotherapy costs. By 2013, after chemotherapy drug
      patent expiry, GEMVIN became the least costly regimen. Economic considerations in
      oncology change over time, and should be revisited in policy decisions based on
      cost.

PMID- 23962450
TI  - Urban-rural differences in adolescent eating behaviour: a multilevel cross
      sectional study of 15-year-olds in Scotland.
AB  - OBJECTIVE: Improving the diet of the Scottish population has been a government
      focus in recent years. Population health is known to vary between geographies;
      therefore alongside trends and socio-economic inequalities in eating behaviour,
      geographic differences should also be monitored. DESIGN: Eating behaviour data
      from the 2010 Scotland Health Behaviour in School-aged Children survey were
      modelled using multilevel linear and logistic modelling. SETTING: Data were
      collected in schools across urban and rural Scotland. SUBJECTS: Schoolchildren
      aged 15 years. RESULTS: Adolescents living in remote rural Scotland had the
      highest consumption frequency of vegetables (on average consumed on 6.68 d/week)
      and the lowest consumption frequency of sweets and crisps (on 4.27 and 3.02
      d/week, respectively). However, it was not in the major four cities of Scotland
      (Glasgow, Edinburgh, Dundee and Aberdeen) but in the geography described by the
      classification 'other urban' areas (large towns of between 10 000 and 125 000
      residents) that adolescents had the poorest diet. Deprivation and rurality were
      independently associated with food consumption for all but fruit consumption.
      Sharing a family meal, dieting behaviour, food poverty and breakfast consumption
      did not differ by rurality. Variance at the school level was significant for
      fruit and vegetable consumption frequencies and for irregular breakfast
      consumption, regardless of rurality. CONCLUSIONS: Young people from rural areas
      have a healthier diet than those living in urban areas. The eating behaviours
      examined did not explain these differences. Future research should investigate
      why urban-rural differences exist for consumption frequencies of 'healthy' and
      'unhealthy' foods.

PMID- 23962451
TI  - Improving access to electronic health records for people with intellectual
      disability: a qualitative study.
AB  - People with intellectual disability represent ~2-3% of the Australian population
      and experience elevated rates of mortality and morbidity compared with the
      general population. People with intellectual disability, and their families and
      carers, must keep track of extensive medical information while also managing
      turnover of paid staff, general practitioners and other health professionals,
      making them beneficiaries of Australia's new eHealth record system. Although they
      are key users, there is a lack of knowledge about the accessibility of the system
      for individuals with intellectual disability, or those responsible for managing
      their health information. This is a missed opportunity to improve the lives of an
      already overlooked group. This study aimed to identify the facilitators and
      barriers to registering for an eHealth record network for people with
      intellectual disability and those supporting them to manage their health
      information. We interviewed potential users of eHealth records, including four
      people with intellectual disability, three family members and two residential
      support workers. Our findings suggest that decision-makers involved in the roll
      out of the eHealth record networks should incorporate 'reasonable accommodations'
      to improve accessibility for people with intellectual disability and those who
      support them to manage their health information. This includes identifying and
      eliminating the barriers to accessibility of eHealth records and taking
      appropriate measures to promote access to individuals with intellectual
      disability. People with intellectual disability and the people who support them
      are a diverse group with a range of abilities. The translation of their views
      into practice will help to improve the eHealth system for this and other
      vulnerable population groups. 

PMID- 23962452
TI  - Urinary concentrations of environmental contaminants and phytoestrogens in adults
      in Israel.
AB  - BACKGROUND: The Ministry of Health Biomonitoring Study estimated exposure of
      individuals in the Israeli population to bisphenol A (BPA), organophosphate (OP)
      pesticides, phthalates, cotinine, polycyclic aromatic hydrocarbons (PAHs), and
      the phytoestrogenic compounds genistein and daidzein. METHODS: In 2011, 250
      individuals (ages 20-74) were recruited from five different regions in Israel.
      Urine samples were collected and questionnaire data were obtained, including
      detailed dietary data (food frequency questionnaire and 24hour recall). Urinary
      samples were analyzed for BPA, OP metabolites (dialkyl phosphates), phthalate
      metabolites, cotinine, PAH metabolites, genistein, and daidzein. RESULTS AND
      DISCUSSION: BPA urinary concentrations were above the limit of quantification
      (LOQ) in 89% of the samples whereas urinary concentrations of phthalate
      metabolites were above the LOQ in 92-100% of the samples. PAH metabolites were
      above the LOQ in 63-99% of the samples whereas OP metabolites were above the LOQ
      in 44-100% of the samples. All non-smoking participants had detectable levels of
      cotinine in their urine; 63% had levels above the LOQ, and the rate of
      quantification was high compared to the general non-smoking population in Canada.
      Median creatinine adjusted concentrations of several OP metabolites (dimethyl
      phosphate, dimethyl thiophosphate) were high in our study population compared to
      the general US and Canadian populations. Median creatinine adjusted urinary BPA
      concentrations in the study population were comparable to those in Belgium and
      Korea; higher than those reported for the general US, German, and Canadian
      populations; and very low compared to health-based threshold values. Phthalate
      concentrations were higher in our study population compared to the general US
      population but values were very low compared to health-based threshold values.
      Median creatinine adjusted PAH concentrations were generally comparable to those
      reported for the general US population; median creatinine adjusted daidzein
      concentrations were high in our population compared to the general US population
      whereas genistein concentrations were comparable. CONCLUSIONS: We interpreted
      observed urinary contaminant levels observed in our study by comparing values
      with health-based threshold values and/or values from international human
      biomonitoring studies. Using this data interpretation scheme, we identified two
      contaminants as being of potential public health concern and high priority for
      public health policy intervention: environmental tobacco smoke (ETS) and OP
      pesticides. We used the data collected in this study to support public health
      policy interventions. We plan to conduct a follow-up biomonitoring study in 2015
      to measure ETS and OP exposure in the general population in Israel, to evaluate
      the effectiveness of relevant policy interventions.

PMID- 23962453
TI  - ACE2 - from the renin-angiotensin system to gut microbiota and malnutrition.
AB  - The renin-angiotensin system (RAS) is a complex network that regulates blood
      pressure, electrolyte and fluid homeostasis, as well as the function of several
      organs. Angiotensin-converting enzyme 2 (ACE2) was identified as an enzyme that
      negatively regulates the RAS by converting Ang II, the main bioactive molecule of
      the RAS, to Ang 1-7. Thus, ACE2 counteracts the role of angiotensin-converting
      enzyme (ACE) which generates Ang II from Ang I. ACE and ACE2 have been implicated
      in several pathologies such as cardiovascular and renal disease or acute lung
      injury. In addition, ACE2 has functions independent of the RAS: ACE2 is the
      receptor for the SARS coronavirus and ACE2 is essential for expression of neutral
      amino acid transporters in the gut. In this context, ACE2 modulates innate
      immunity and influences the composition of the gut microbiota, which can explain
      diarrhea and intestinal inflammation observed in Hartnup disorder, Pellagra, or
      under conditions of severe malnutrition. Here we review and discuss the diverse
      functions of ACE2 and its relevance to human pathologies. 

PMID- 23962454
TI  - Cell-type-specific regulation of genes involved in testicular lipid metabolism:
      fatty acid-binding proteins, diacylglycerol acyltransferases, and perilipin 2.
AB  - Male germ cell differentiation entails the synthesis and remodeling of membrane
      polar lipids and the formation of triacylglycerols (TAGs). This requires fatty
      acid-binding proteins (FABPs) for intracellular fatty acid traffic, a
      diacylglycerol acyltransferase (DGAT) to catalyze the final step of TAG
      biosynthesis, and a TAG storage mode. We examined the expression of genes
      encoding five members of the FABP family and two DGAT proteins, as well as the
      lipid droplet protein perilipin 2 (PLIN2), during mouse testis development and in
      specific cells from seminiferous epithelium. Fabp5 expression was distinctive of
      Sertoli cells and consequently was higher in prepubertal than in adult testis.
      The expression of Fabp3 increased in testis during postnatal development,
      associated with the functional differentiation of interstitial cells, but was low
      in germ cells. Fabp9, together with Fabp12, was prominently expressed in the
      latter. Their transcripts increased from spermatocytes to spermatids and,
      interestingly, were highest in spermatid-derived residual bodies (RB). Both
      Sertoli and germ cells, which produce neutral lipids and store them in lipid
      droplets, expressed Plin2. Yet, while Dgat1 was detected in Sertoli cells, Dgat2
      accumulated in germ cells with a similar pattern of expression as Fabp9. These
      results correlated with polyunsaturated fatty acid-rich TAG levels also
      increasing with mouse germ cell differentiation highest in RB, connecting DGAT2
      with the biosynthesis of such TAGs. The age- and germ cell type-associated
      increases in Fabp9, Dgat2, and Plin2 levels are thus functionally related in the
      last stages of germ cell differentiation. 

PMID- 23962455
TI  - Head-to-head comparison of subcutaneous abatacept versus adalimumab for
      rheumatoid arthritis: two-year efficacy and safety findings from AMPLE trial.
AB  - OBJECTIVES: To compare over 2 years the safety, efficacy and radiographic
      outcomes of subcutaneous abatacept versus adalimumab, in combination with
      methotrexate (MTX), in patients with rheumatoid arthritis (RA). METHODS: AMPLE is
      a phase IIIb, 2-year, randomised, investigator-blinded study with a 1-year
      primary endpoint. Biologic-naive patients with active RA and an inadequate
      response to MTX were randomised to 125 mg abatacept weekly or 40 mg adalimumab bi
      weekly, both with a stable dose of MTX. RESULTS: Of 646 patients randomised,
      79.2% abatacept and 74.7% adalimumab patients completed year 2. At year 2,
      efficacy outcomes, including radiographic, remained comparable between groups and
      with year 1 results. The American College Rheumatology 20, 50 and 70 responses at
      year 2 were 59.7%, 44.7% and 31.1% for abatacept and 60.1%, 46.6% and 29.3% for
      adalimumab. There were similar rates of adverse events (AEs) and serious adverse
      events (SAEs). More serious infections occurred with adalimumab (3.8% vs 5.8%)
      including two cases of tuberculosis with adalimumab. There were fewer
      discontinuations due to AEs (3.8% vs 9.5%), SAEs (1.6% vs 4.9%) and serious
      infections (0/12 vs 9/19 patients) in the abatacept group. Injection site
      reactions (ISRs) occurred less frequently with abatacept (4.1% vs 10.4%).
      CONCLUSIONS: Through 2 years of blinded treatment in this first head-to-head
      study between biologic disease-modifying antirheumatic drugs in RA patients with
      an inadequate response to MTX, subcutaneous abatacept and adalimumab were
      similarly efficacious based on clinical, functional and radiographic outcomes.
      Overall, AE frequency was similar in both groups but there were less
      discontinuations due to AEs, SAEs, serious infections and fewer local ISRs with
      abatacept.

PMID- 23962456
TI  - Prediction model for knee osteoarthritis incidence, including clinical, genetic
      and biochemical risk factors.
AB  - OBJECTIVE: To develop and validate a prognostic model for incident knee
      osteoarthritis (KOA) in a general population and determine the value of different
      risk factor groups to prediction. METHODS: The prognostic model was developed in
      2628 individuals from the Rotterdam Study-I (RS-I). Univariate and multivariate
      analyses were performed for questionnaire/easily obtainable variables, imaging
      variables, genetic and biochemical markers. The extended multivariate model was
      tested on discrimination (receiver operating characteristic curve and area under
      the curve (AUC)) in two other population-based cohorts: Rotterdam Study-II and
      Chingford Study. RESULTS: In RS-I, there was moderate predictive value for
      incident KOA based on the genetic score alone in subjects aged <65 years (AUC
      0.65), while it was only 0.55 for subjects aged >=65 years. The AUC for gender,
      age and body mass index (BMI) in prediction for KOA was 0.66. Addition of the
      questionnaire variables, genetic score or biochemical marker urinary C-terminal
      cross-linked telopeptide of type II collagen to the model did not change the AUC.
      However, when adding the knee baseline KL score to the model the AUC increased to
      0.79. Applying external validation, similar results were observed in the
      Rotterdam Study-II and the Chingford Study. CONCLUSIONS: Easy obtainable
      'Questionnaire' variables, genetic markers, OA at other joint sites and
      biochemical markers add only modestly to the prediction of KOA incidence using
      age, gender and BMI in an elderly population. Doubtful minor radiographic
      degenerative features in the knee, however, are a very strong predictor of future
      KOA. This is an important finding, as many radiologists do not report minor
      degenerative changes in the knee.

PMID- 23962457
TI  - Impact of the European paediatric legislation in paediatric rheumatology: past,
      present and future.
AB  - Conducting clinical trials in paediatric rheumatology has been difficult mainly
      because of the lack of funding for academic studies and the lack of interest by
      pharmaceutical companies in the small and non-rewarding paediatric market. The
      situation changed dramatically a few years ago with the introduction of the Best
      Pharmaceuticals for Children Act in the USA and of specific legislation for the
      development of paediatric medicines (Paediatric Regulation) in the European Union
      (EU). The EU Paediatric Regulation had a positive impact in paediatric
      rheumatology-in particular, on the development of new treatments for children
      with juvenile idiopathic arthritis (JIA). Some problems remain, however, such as
      greater harmonisation of the regulatory aspects of medicines, how to handle me
      too agents, how to conduct adequate pharmacokinetic studies and develop age
      appropriate formulations, ethical problems in study review and implementation,
      and a change in the current JIA classification. The introduction of specific
      legislation, coupled with the existence of large international networks such as
      the Pediatric Rheumatology Collaborative Study Group (PRCSG at
      http://www.prcsg.org), covering North America, and the Paediatric Rheumatology
      International Trials Organisation (PRINTO at http://www.printo.it), covering more
      than 50 countries, has led to great advances in paediatric rheumatology. Future
      changes might increase the possibility of conducting trials with similar
      approaches in other paediatric rheumatological conditions and provide evidence
      based treatments for children affected by rheumatic diseases. 

PMID- 23962458
TI  - Prevalence and incidence rates of psoriatic arthritis in central Norway: data
      from the Nord-Trondelag health study (HUNT).
AB  - BACKGROUND: A wide range in the prevalence (<0.01-0.25%) and incidence (0.5
      23.1/100 000) of psoriatic arthritis (PsA) is reported. The main objective of
      this study was to examine the prevalence and incidence of PsA in central Norway.
      METHOD: The patients were recruited from the Nord-Trondelag Health Study 3, a
      population study carried out in 2006-2008. All 94 194 inhabitants aged >20 years
      were invited and 50 806 (54%) responded. The study consisted of a questionnaire
      (Q1) and a brief medical examination. Q1 included questions if the persons
      suffered from psoriasis, rheumatoid arthritis (RA) or ankylosing spondylitis
      (AS). Patients with self-reported psoriasis further answered a specific
      questionnaire on psoriasis including a questionnaire concerning PsA. In order to
      identify patients with PsA we used the following criteria: Persons reporting they
      had or may have PsA; persons answering that they had psoriasis and RA; and
      persons answering that they had psoriasis and AS. Using this approach, 1278
      patients were identified. Hospital files were evaluated by a rheumatologist
      according to a predefined protocol to verify the diagnosis of PsA. RESULTS: 338
      patients, 144 men and 194 women, were verified to have PsA. The prevalence of PsA
      was 6.7 (95% CI 5.9 to 7.4) per 1000 inhabitants >20 years with no significant
      difference between men and women. In the 9-year period of 2000-2008, a total of
      188 patients were diagnosed with PsA, which give an incidence rate of 41.3/100
      000 (35.8-47.6). CONCLUSIONS: The prevalence of PsA in central Norway appears to
      be higher than previously reported. The reason for this is unknown and may
      include environmental factors, life style factors and genetic differences.

PMID- 23962460
TI  - Hypothermic versus normothermic cardiopulmonary bypass in patients with valvular
      heart disease.
AB  - OBJECTIVE: The aim of this study was to test the hypothesis that normothermic
      cardiopulmonary bypass (CPB) is as effective as hypothermic CPB in terms of
      cardiac protection (cTnI level) and outcome in patients with valvular heart
      disease. DESIGN: Prospective randomized study. SETTING: A tertiary cardiothoracic
      referral center. PARTICIPANTS: 140 patients who had valvular heart disease,
      with/without coronary artery disease, surgically treated under CPB.
      INTERVENTIONS: The patients were allocated randomly to undergo either hypothermic
      (temperature [T], 31  degrees C-32  degrees C) or normothermic CPB (T>36  degrees
      C). MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the dynamics of
      troponin I. The secondary endpoints were ventilation time, the need for inotropic
      support, intensive care unit (ICU) and hospital stay durations, complications,
      and mortality. There were no significant intergroup differences in dynamics of
      troponin I. Ventilation time was significantly lower in the hypothermic group (6
      (5-9) and 8 (5-12); p = 0.01). CONCLUSIONS: Normothermic CPB in patients with
      valvular heart disease was as effective as hypothermic perfusion in terms of
      myocardial protection after the surgery assessed by cTnI release. The short
      ventilation duration in patients who underwent hypothermic CPB needs to be
      confirmed in a future investigation.

PMID- 23962459
TI  - Transfusion of allogeneic blood products in proximal aortic surgery with
      hypothermic circulatory arrest: effect of thromboelastometry-guided transfusion
      management.
AB  - OBJECTIVES: Proximal aortic surgery with hypothermic circulatory arrest (HCA)
      commonly involves perioperative transfusion of allogeneic blood products,
      including red blood cells, plasma, and platelets. The authors hypothesized that
      surgery with HCA could be performed without allogeneic blood products and that a
      thromboelastometry-guided algorithm would reduce the transfusion of allogeneic
      blood products. DESIGN: A retrospective analysis of prospectively collected data.
      Patients with and without thromboelastometry guidance were compared by case
      control analysis (n = 62 matched patients) and multivariate regression (n = 194
      patients). SETTING: Single-center university hospital. PARTICIPANTS: This study
      included 194 patients undergoing elective and emergent procedures with HCA
      involving the proximal aorta. INTERVENTIONS: A thromboelastometry-guided
      treatment algorithm during surgery was used in 153 patients (79%), and
      conventional coagulation management was used in 41 patients (21%). MEASUREMENTS
      AND MAIN RESULTS: During surgery and the following 24 hours, allogeneic blood
      products were transfused in 106 patients (55%). Median (interquartile range)
      number of allogeneic blood products transfused was 1 unit (0-6 units). Case
      control analysis showed lower transfusion rates of red blood cells, plasma, and
      any allogeneic blood product (all p<0.050) in patients with thromboelastometry
      guidance. In the multivariate analysis, thromboelastometry guidance was
      associated with an odds ratio of 0.26 (95% confidence interval, 0.08-0.84; p =
      0.025) for the transfusion of any allogeneic blood product. The use of
      thromboelastometry was not associated with adverse events (odds ratio 0.72; 95%
      confidence interval, 0.27-1.90; p = 0.507). CONCLUSIONS: Allogeneic blood
      products were avoided in a proportion of patients. The findings further suggest
      that thromboelastometry-guided coagulation management promoting the use of
      coagulation factor concentrates decreased the use of allogeneic blood products
      during complex cardiac surgery.

PMID- 23962461
TI  - The problem of controlling for imperfectly measured confounders on dissimilar
      populations: a database simulation study.
AB  - OBJECTIVE(S): Observational database research frequently relies on imperfect
      administrative markers to determine comorbid status, and it is difficult to infer
      to what extent the associated misclassification impacts validity in multivariable
      analyses. The effect that imperfect markers of disease will have on validity in
      situations in which researchers attempt to match populations that have strong
      baseline health differences is underemphasized as a limitation in some otherwise
      high-quality observational studies. The present simulations were designed as a
      quantitative demonstration of the importance of this common and underappreciated
      issue. DESIGN: Two groups of Monte Carlo simulations were performed. The first
      demonstrated the degree to which controlling for a series of imperfect markers of
      disease between different populations taking 2 hypothetically harmless drugs
      would lead to spurious associations between drug assignment and mortality. The
      second Monte Carlo simulation applied this principle to a recent study in the
      field of anesthesiology that purported to show increased perioperative mortality
      in patients taking metoprolol versus atenolol.
      SETTING/PARTICIPANTS/INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Simulation 1: High type-1 error (ie, false positive findings of an independent
      association between drug assignment and mortality) was observed as sensitivity
      and specificity declined and as systematic differences in disease prevalence
      increased. Simulation 2: Propensity score matching across several imperfect
      markers was unlikely to eliminate important baseline health disparities in the
      referenced study. CONCLUSIONS: In situations in which large baseline health
      disparities exist between populations, matching on imperfect markers of disease
      may result in strong bias away from the null hypothesis.

PMID- 23962462
TI  - Mitral annulus: an intraoperative echocardiographic perspective.

PMID- 23962463
TI  - Global lessons on transforming strategy into action to save mothers' lives.
AB  - Although many countries remain far from achieving the reduction in maternal
      mortality stipulated by Millennium Development Goal (MDG) 5, 13 are on track to
      achieve this goal-despite experiencing similar fiscal, workforce, and other
      constraints as lower-performing peers. The present article assesses existing
      literature and successful local examples to allow health leaders to learn from
      these global success stories. A key lesson is that clinical interventions are not
      enough. Basic care provision must be supplemented with interventions that
      stimulate demand for services and ensure that they are both affordable and
      physically accessible. At US $1-6 per woman, comprehensive programs need not
      exert unsustainable pressure on health budgets. But perhaps more important is how
      this "ecosystem" of interventions is implemented. We identify 5 principles that
      characterize successful implementation: embedding maternal health as a top
      priority; focusing on targeted effective initiatives; fostering strong local
      ownership; maximizing efficiency and use of available resources; and creating a
      tough system of national accountability. Together, they offer policymakers and
      health leaders principles with which to accelerate progress toward MDG 5. With so
      many women's lives at stake, there could hardly be a greater incentive to do so. 

PMID- 23962464
TI  - Infiltrating gluteal fibrosarcoma presenting as back pain in pregnancy.

PMID- 23962465
TI  - Ovarian function preserved by carbon-ion radiotherapy for alveolar soft-part
      sarcoma.

PMID- 23962466
TI  - The use of a modified [3H]4-DAMP radioligand binding assay with increased
      selectivity for muscarinic M3 receptor shows that cortical CHRM3 levels are not
      altered in mood disorders.
AB  - [(3)H]4-DAMP is a radioligand that has been used to quantify levels of the
      muscarinic receptor CHRM3 protein in situ. However, in addition to high affinity
      binding to CHRM3, [(3)H]4-DAMP binds with low affinity to CHRM1 confounding the
      potential to discriminate between changes in these two muscarinic receptors. We
      have developed a [(3)H]4-DAMP binding assay, optimised for measuring CHRM3
      protein levels in the cortex, with minimal selectivity towards CHRM1. The
      selectivity of our assay towards CHRM3 was confirmed using recombinant receptor
      expressing, cell lysate preparations. [(3)H]4-DAMP binding levels were similar
      between wildtype and CHRM1 knockout mice, confirming that the amount of [(3)H]4
      DAMP binding to CHRM1 was negligible. We used this assay to measure CHRM3 protein
      levels in the frontal pole, obtained post-mortem from subjects with bipolar
      disorder (n = 15), major depressive disorder (n = 15) and matched controls (n =
      20) and showed that [(3)H]4-DAMP binding was not altered in either bipolar
      disorder or major depressive disorder. Western blotting confirmed that CHRM3
      protein levels were unchanged in these subjects.

PMID- 23962467
TI  - Genetic lineages of Salmonella enterica serovar Kentucky spreading in pet
      reptiles.
AB  - The purpose of the study was to define genetic diversity of reptilian Salmonella
      enterica serovar (S.) Kentucky isolates and their epidemiological relations to
      the ones from poultry, food, and environmental origin in Poland. Between 2010 and
      2012 twenty-four S. Kentucky isolates derived from snakes (N=8), geckos (N=7),
      chameleons (N=4), agamas (N=1), lizard (N=1), and environmental swabs taken from
      reptile exhibition (N=3) were identified. They were characterized with
      antimicrobial minimal inhibitory concentration testing, XbaI-PFGE and MLST
      typing. The profiles compared to S. Kentucky available in BioNumerics local
      laboratory database (N=40) showed 67.3% of relatedness among reptile isolates.
      Three genetic lineages were defined. The first lineage gathered 20 reptile
      isolates with 83.4% of similarity and wild-type MICs for all antimicrobials
      tested but streptomycin in single case. The remaining three reptilian and one
      post-exhibition environment S. Kentucky isolates were clustered (87.2%) with
      isolates originating from poultry, mainly turkey, food, and environment and
      presented variable non-wild type MICs to numerous antimicrobials. The third S.
      Kentucky lineage was composed of two isolates from feed (96.3%). The results
      suggest diverse sources and independent routes of infection. Most of the isolates
      belonged to reptile-associated clones spread both horizontally and vertically.
      Simultaneously, PFGE profiles and MLST type indistinguishable from the ones
      observed in poultry point out carnivore reptiles as possible vector of infection
      with multidrug and high-level ciprofloxacin resistant (MIC>=8 mg/L) S. Kentucky.
      Public awareness and education are required to prevent potential reptile
      associated S. Kentucky infections in humans.

PMID- 23962468
TI  - Neural correlates of inhibition of socially relevant stimuli in adults with
      autism spectrum disorder.
AB  - Adults with autism spectrum disorder (ASD) can demonstrate difficulties with
      inhibiting inappropriate social responses. Presently, little research has
      utilized socially relevant stimuli to explore the modulatory effects of emotion
      on cognitive control in this population. To assess neural mechanisms of
      inhibiting social stimuli, we presented images of happy or sad facial expressions
      in a Go/NoGo task to unmedicated adults with ASD and to controls during
      functional magnetic resonance imaging (fMRI). Groups did not differ on behavioral
      measures. Brain activation in response to NoGo vs. Go trials revealed differing
      regional patterns of activation within groups. Controls recruited brain regions
      involved in inhibition (dorsal- [DLPFC] and ventro-lateral prefrontal cortices
      [VLPFC], anterior cingulate cortex [ACC]), response suppression (parietal lobe),
      interoceptive awareness (insula), and also the fusiform and middle temporal gyri.
      Adults with ASD only recruited the VLPFC and right fusiform gyrus, and weakly
      activated the ACC and insula. Between-group comparisons indicated that controls
      activated the DLPFC, while adults with ASD relied on the VLPFC and the fusiform
      gyrus to inhibit responses. Adults with ASD may have relied more on visual
      association cortex, possibly as a means of recruiting additional neural processes
      that could act as a compensatory mechanism. 

PMID- 23962469
TI  - Microstructural white-matter abnormalities associated with treatment resistance,
      severity and duration of illness in major depression.
AB  - BACKGROUND: Although white-matter abnormalities have been reported in middle-aged
      patients with major depressive disorder (MDD), few data are available on
      treatment-resistant MDD and the influence of relevant variables related to
      clinical burden of illness is far from being well established. METHOD: The
      present study examined white-matter microstructure in a sample of 52 patients
      with MDD in different stages (treatment-resistant/chronic MDD, n = 18; remitted
      recurrent MDD, n = 15; first-episode MDD, n = 19) and 17 healthy controls, using
      diffusion tensor imaging with a tract-based spatial statistics approach. Groups
      were comparable in age and gender distribution, and results were corrected for
      familywise error (FWE) rate. RESULTS: Widespread significant reductions of
      fractional anisotropy (FA) - including the cingulum, corpus callosum, superior
      and inferior longitudinal fascicule - were evident in treatment-resistant/chronic
      MDD compared with first-episode MDD and controls (p < 0.05, FWE-corrected).
      Decreased FA was observed within the ventromedial prefrontal region in treatment
      resistant/chronic MDD even when compared with the remitted-recurrent MDD group (p
      < 0.05, FWE-corrected). Longer duration of illness (beta = -0.49, p = 0.04) and
      higher depression severity (at a trend level: beta = -0.26, p = 0.06) predicted
      lower FA in linear multiple regression analysis at the whole-brain level. The
      number of previous episodes and severity of symptoms were significant predictors
      when focused on the ventromedial prefrontal area (beta = -0.28, p = 0.04; and
      beta = -0.29, p = 0.03, respectively). Medication effects were controlled for in
      the analyses and results remained unaltered. CONCLUSIONS: Our findings support
      the notion that disruptions of white-matter microstructure, particularly in
      fronto-limbic networks, are associated with resistance to treatment and higher
      current and past burden of depression.

PMID- 23962470
TI  - Analgesic effects of intrathecal tramadol in patients undergoing caesarean
      section: a randomised, double-blind study.
AB  - BACKGROUND: Intrathecal tramadol combined with local anaesthetics has been used
      for postoperative analgesia following lower abdominal and perineal surgery. The
      present study evaluated the effect of intrathecal tramadol on spinal block
      characteristics and neonatal outcome after elective caesarean section. METHODS:
      Eighty full-term parturients scheduled for elective caesarean section were
      randomly divided into two groups. In the fentanyl group, patients received
      intrathecal 0.5% bupivacaine 10 mg with fentanyl 10 MUg; in the tramadol group,
      patients were given the same dose of bupivacaine with tramadol 10 mg. Sensory and
      motor block characteristics, duration of postoperative analgesia, maternal side
      effects, and neonatal outcome were compared. RESULTS: One patient in the tramadol
      group and two patients in the fentanyl group were excluded from data analysis.
      Median [interquartile range] duration of postoperative analgesia in the tramadol
      and the fentanyl groups was 300 [240-360] min and 260 [233-300] min respectively
      (P = 0.02). The incidence of shivering was lower in patients who received
      tramadol (5%) than those who had fentanyl (32%) (P = 0.003). Apgar scores,
      umbilical cord acid-base measurement and neurologic and adaptive capacity scores
      were comparable between the two groups. CONCLUSION: Compared to intrathecal
      fentanyl 10 MUg, tramadol 10 mg, as an adjunct to bupivacaine for subarachnoid
      block for caesarean section, showed a longer duration of analgesia with a reduced
      incidence of shivering.

PMID- 23962471
TI  - Assessing blocks after spinal anaesthesia for elective caesarean section: how
      different questions affect findings from the same stimulus.
AB  - BACKGROUND: A block to touch to T5 is widely used to indicate an adequate level
      of block for caesarean section with spinal anaesthesia. However, two studies
      using a "block to light touch" to T5 as their end-point, had a high requirement
      for intraoperative analgesia and their results cast doubt on the adequacy of a
      block to touch to T5. On enquiry, these two papers did not assess complete block
      to touch, but asked mothers when the touch sensation "was the same as" a control
      stimulus. The difference between these two assessment methods is unknown. The
      current study presents prospectively collected sensory block data which included
      both block to touch and the level when touch was the same as a control stimulus.
      METHODS: The levels of block were assessed using a Neurotip(r). The mother was
      asked four questions to assess the block: first touch level, first sharp level,
      touch same as control and sharp same as control. RESULTS: The first touch level
      was a median of two dermatomes lower than the touch same as a control level [IQR
      0-3, range 0-6]. Block level assessment methods using first sharp and touch same
      as control were equivalent. CONCLUSION: When describing a sensory block, not only
      is it necessary to indicate the exact stimulus used, but it is important to
      define the actual question asked of the patient. Clinically, block assessment
      using the first sharp level and touch same as control are equivalent.

PMID- 23962472
TI  - Relationships between intuitive eating and health indicators: literature review.
AB  - OBJECTIVE: To review the peer-reviewed literature on relationships between
      intuitive eating and health indicators and suggest areas of inquiry for future
      research. We define the fundamental principles of intuitive eating as: (i) eating
      when hungry; (ii) stopping eating when no longer hungry/full; and (iii) no
      restrictions on types of food eaten unless for medical reasons. DESIGN: We
      include articles cited by PubMed, PsycInfo and Science Direct published in peer
      reviewed journals or theses that include 'intuitive eating' or related concepts
      in the title or abstract and that test relationships between intuitive eating and
      physical or mental health indicators. RESULTS: We found twenty-six articles that
      met our criteria: seventeen cross-sectional survey studies and nine clinical
      studies, eight of which were randomised controlled trials. The cross-sectional
      surveys indicate that intuitive eating is negatively associated with BMI,
      positively associated with various psychological health indicators, and possibly
      positively associated with improved dietary intake and/or eating behaviours, but
      not associated with higher levels of physical activity. From the clinical
      studies, we conclude that the implementation of intuitive eating results in
      weight maintenance but perhaps not weight loss, improved psychological health,
      possibly improved physical health indicators other than BMI (e.g. blood pressure;
      cholesterol levels) and dietary intake and/or eating behaviours, but probably not
      higher levels of physical activity. CONCLUSIONS: Research on intuitive eating has
      increased in recent years. Extant research demonstrates substantial and
      consistent associations between intuitive eating and both lower BMI and better
      psychological health. Additional research can add to the breadth and depth of
      these findings. The article concludes with several suggestions for future
      research.

PMID- 23962473
TI  - Sexual behaviours and associated risks in Chinese young people: a meta-analysis.
AB  - BACKGROUND: The earlier and unprotected sexual behaviour of young Chinese, and
      the consequences of these actions, have become a health concern, posing a
      challenge to traditional Chinese concepts. The aim of the present study was to
      investigate changes in sexual behaviour and associated risks among adolescents
      and young people in mainland China over the past three decades. METHODS: A meta
      analysis was undertaken to comprehensively review the sexual behaviour of Chinese
      young people (aged from 10 to 24 years) over the past 30 years. Relevant data
      published from 1979 to 2009 in the Chinese literature database were identified
      and retrieved. Analysis was performed based on set criteria. RESULTS: Seventy
      five studies were identified that were published after 1990. Overall, the
      estimated prevalence of sexual intercourse among young people was 12.6%, with an
      average age at sexual debut of 19.4 years. The rate of condom use at sexual debut
      was 37.2%; 53.6% of young people reported not using a condom during the most
      recent act of sexual intercourse. The rates of unintentional pregnancy and
      abortion among the sexually active were 15.1% and 10.8%, respectively. Reviewing
      the data according to decades revealed that the number of young people engaging
      in sexual intercourse decreased from 14.3% in 1990-1999 to 11.8% in 2000-2009.
      However, these rates are higher than the prevalence of sexual activity reported
      before 1990, which, according to sporadic studies, did not exceeded 1%.
      CONCLUSIONS: There have been increases in sexual activity and high-risk sexual
      behaviour in Chinese young people in the decades since the adoption of the open
      door policy in China, particularly since the mid-1990s. High-risk sexual
      behaviours have contributed to certain adverse consequences in adolescents and
      young people, such as unwanted pregnancy and sexually transmissible infection.
      Thus, efficacious intervention strategies need to be developed and implemented.

PMID- 23962474
TI  - Severe pre-eclampsia and hypertensive crises.
AB  - Hypertensive disorders of pregnancy are one of the leading causes of peripartum
      morbidity and mortality globally. Hypertensive disease in pregnancy is associated
      with a spectrum of severity, ranging from mild pregnancy-induced hypertension to
      eclampsia. Although most cases of pre-eclampsia may be managed successfully,
      severe pre-eclampsia is a life-threatening multisystem disease associated with
      eclampsia, HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome,
      acute kidney injury, pulmonary oedema, placental abruption and intrauterine
      foetal death. Management of severe pre-eclampsia includes identification of high
      risk patients, optimisation of antenatal care, early intervention and the
      identification and early management of complications. In the first instance, oral
      anti-hypertensive agents, including labetalol, nifedipine and methyldopa, should
      be tried. If oral anti-hypertensive agents have failed to adequately control
      blood pressure, intravenous anti-hypertensives should be considered. Commonly
      used intravenous anti-hypertensives include labetalol, hydralazine and glyceryl
      trinitrate. In addition to anti-hypertensive agents, close attention should be
      given to regular clinical examination, assessment of fluid balance, neurologic
      status and monitoring of other vital signs. Magnesium sulphate should be
      considered early to prevent seizures. Delivery of the baby is the definitive
      management of severe pre-eclampsia.

PMID- 23962475
TI  - EMDS 2012: 26th Meeting of the European Society for Macrophage and Dendritic Cell
      Biology in Debrecen, Hungary, September 1-3, 2012.

PMID- 23962476
TI  - The interferon response to intracellular DNA: why so many receptors?
AB  - The detection of intracellular DNA has emerged to be a key event in the innate
      immune response to viruses and intracellular bacteria, and during conditions of
      sterile inflammation and autoimmunity. One of the consequences of the detection
      of DNA as a 'stranger' and a 'danger' signal is the production of type I
      interferons and pro-inflammatory cytokines. Much work has been dedicated to the
      elucidation of the signalling cascades that activate this DNA-induced gene
      expression programme. However, while many proteins have been proposed to act as
      sensors for intracellular DNA in recent years, none has been met with universal
      acceptance, and a theory linking all the recent observations is, as yet, lacking.
      This review presents the evidence for the various interferon-inducing DNA
      receptors proposed to date, and examines the hypotheses that might explain why so
      many different receptors appear to be involved in the innate immune recognition
      of intracellular DNA. 

PMID- 23962477
TI  - microRNA control of interferons and interferon induced anti-viral activity.
AB  - Interferons (IFNs) are cytokines that are spontaneously produced in response to
      virus infection. They act by binding to IFN-receptors (IFN-R), which trigger
      JAK/STAT cell signalling and the subsequent induction of hundreds of IFN
      inducible genes, including both protein-coding and microRNA genes. IFN-induced
      genes then act synergistically to prevent virus replication and create an anti
      viral state. miRNA are therefore integral to the innate response to virus
      infection and are important components of IFN-mediated biology. On the other hand
      viruses also encode miRNAs that in some cases interfere directly with the IFN
      response to infection. This review summarizes the important roles of miRNAs in
      virus infection acting both as IFN-stimulated anti-viral molecules and as
      critical regulators of IFNs and IFN-stimulated genes. It also highlights how
      recent knowledge in RNA editing influence miRNA control of virus infection. 

PMID- 23962478
TI  - Biofunctionalisation of electrically conducting polymers.
AB  - During a single decade of research, evidence has emerged that glial scar
      formation around the electro-tissue interface drives neural loss and increases
      the signal impedance of the electrodes, compromising the efficiency of the
      stimulating systems. Studies with conducting polymers (CPs) as electrode coatings
      have shown enhanced tissue integration and electrode performance in situ through
      biochemical and physicomechanical functionalisation. In this review, recent
      findings on CP modifications are provided in the context of neurospecific
      biomaterials, shedding light on the valuable impact of multifunctionalised
      strategies for biomedical applications. 

PMID- 23962479
TI  - A comparative study of statistical methods used to identify dependencies between
      gene expression signals.
AB  - One major task in molecular biology is to understand the dependency among genes
      to model gene regulatory networks. Pearson's correlation is the most common
      method used to measure dependence between gene expression signals, but it works
      well only when data are linearly associated. For other types of association, such
      as non-linear or non-functional relationships, methods based on the concepts of
      rank correlation and information theory-based measures are more adequate than the
      Pearson's correlation, but are less used in applications, most probably because
      of a lack of clear guidelines for their use. This work seeks to summarize the
      main methods (Pearson's, Spearman's and Kendall's correlations; distance
      correlation; Hoeffding's D: measure; Heller-Heller-Gorfine measure; mutual
      information and maximal information coefficient) used to identify dependency
      between random variables, especially gene expression data, and also to evaluate
      the strengths and limitations of each method. Systematic Monte Carlo simulation
      analyses ranging from sample size, local dependence and linear/non-linear and
      also non-functional relationships are shown. Moreover, comparisons in actual gene
      expression data are carried out. Finally, we provide a suggestive list of methods
      that can be used for each type of data set. 

PMID- 23962480
TI  - Nutrition in the very low birth weight infant.

PMID- 23962481
TI  - Community-acquired pneumonia in children.
AB  - Community-acquired pneumonia (CAP) remains a frequent cause of morbidity and
      mortality worldwide even in industrialised countries, and its incidence is
      highest among children aged <5 years. Over the last two years, three
      international guidelines have been updated with new evidence concerning the
      incidence, aetiology and management of childhood CAP, but there are still some
      major problems in standardisation. The main aim of this review is to consider the
      available data concerning the aetiology, diagnosis, evaluation of severity, and
      treatment of paediatric CAP. Analysis of the literature shows that there are a
      number of unanswered questions concerning the management of CAP, including its
      definition, the absence of a paediatric CAP severity score, the difficulty of
      identifying its aetiology, the emergence of resistance of the most frequent
      respiratory pathogens to the most widely used anti-infectious agents, and the
      lack of information concerning the changes in CAP epidemiology following the
      introduction of vaccines against respiratory pathogens. More research is clearly
      required in various areas, and further efforts are needed to increase vaccination
      coverage with the already available vaccines in order to reduce the occurrence of
      the disease.

PMID- 23962482
TI  - Feeding intolerance in the preterm infant.
AB  - Feeding intolerance (FI), defined as the inability to digest enteral feedings
      associated to increased gastric residuals, abdominal distension and/or emesis, is
      frequently encountered in the very preterm infant and often leads to a disruption
      of the feeding plan. In most cases FI represents a benign condition related to
      the immaturity of gastrointestinal function, however its presentation may largely
      overlap with that of an impending necrotizing enterocolitis. As a consequence,
      individual interpretation of signs of FI represents one of the most
      uncontrollable variables in the early nutritional management of these infants,
      and may lead to suboptimal nutrition, delayed attainment of full enteral feeding
      and prolonged intravenous nutrition supply. Strategies aimed at preventing and/or
      treating FI are diverse, although very few have been validated in large RCT and
      systematic reviews. The purpose of this paper is to summarize the existing
      information on this topic, spanning from patho-physiological and clinical aspects
      to the prevention and treatment strategies tested in clinical studies, with
      specific attention to practical issues. 

PMID- 23962483
TI  - Investigation of kinetic interactions between approved oximes and human
      acetylcholinesterase inhibited by pesticide carbamates.
AB  - Carbamates are widely used for pest control and act primarily by inhibition of
      insect and mammalian acetylcholinesterase (AChE). Accidental or intentional
      uptake of carbamates may result in typical signs and symptoms of cholinergic
      overstimulation which cannot be discriminated from those of organophosphorus
      pesticide poisoning. There is an ongoing debate whether standard treatment with
      atropine and oximes should be recommended for human carbamate poisoning as well,
      since in vitro and in vivo animal data indicate a deleterious effect of oximes
      when used in combination with the N-methyl carbamate carbaryl. Therefore, we
      performed an in vitro kinetic study to investigate the effect of clinically used
      oximes on carbamoylation and decarbamoylation of human AChE. It became evident
      that pralidoxime and obidoxime in therapeutic concentrations aggravate the
      inhibition of AChE by carbaryl and propoxur, with obidoxime being substantially
      more potent compared to 2-PAM. However, obidoxime had no impact on the
      decarbamoylation kinetics. Hence, the administration of 2-PAM and especially of
      obidoxime to severely propoxur and carbaryl poisoned humans cannot be
      recommended. 

PMID- 23962484
TI  - Cost-effectiveness of combining systematic identification and treatment of co
      morbid major depression for people with chronic diseases: the example of cancer.
AB  - BACKGROUND: Co-morbid major depression occurs in approximately 10% of people
      suffering from a chronic medical condition such as cancer. Systematic integrated
      management that includes both identification and treatment has been advocated.
      However, we lack information on the cost-effectiveness of this combined approach,
      as published evaluations have focused solely on the systematic (collaborative
      care) treatment stage. We therefore aimed to use the best available evidence to
      estimate the cost-effectiveness of systematic integrated management (both
      identification and treatment) compared with usual practice, for patients
      attending specialist cancer clinics. METHOD: We conducted a cost-effectiveness
      analysis using a decision analytic model structured to reflect both the
      identification and treatment processes. Evidence was taken from reviews of
      relevant clinical trials and from observational studies, together with data from
      a large depression screening service. Sensitivity and scenario analyses were
      undertaken to determine the effects of variations in depression incidence rates,
      time horizons and patient characteristics. RESULTS: Systematic integrated
      depression management generated more costs than usual practice, but also more
      quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio
      (ICER) was L11,765 per QALY. This finding was robust to tests of uncertainty and
      variation in key model parameters. CONCLUSIONS: Systematic integrated management
      of co-morbid major depression in cancer patients is likely to be cost-effective
      at widely accepted threshold values and may be a better way of generating QALYs
      for cancer patients than some existing medical and surgical treatments. It could
      usefully be applied to other chronic medical conditions.

PMID- 23962485
TI  - Do either early warning systems or emergency response teams improve hospital
      patient survival? A systematic review.
AB  - BACKGROUND: For critical care to be effective it must have a system in place to
      achieve optimal care for the deteriorating ward patient. OBJECTIVES: To
      systematically review the available literature to assess whether either early
      warning systems or emergency response teams improve hospital survival. In the
      event of there being a lack of evidence regarding hospital survival, secondary
      outcome measures were considered (unplanned ICU admissions, ICU mortality, length
      of ICU stay, length of hospital stay, cardiac arrest rates). METHODS: The Ovid
      Medline, EMBASE, CINAHL, Web of Science, Cochrane library and NHS databases were
      searched in September 2012 along with non-catalogued resources for papers
      examining the effect of early warning systems or emergency response teams on
      hospital survival. Inclusion criteria were original clinical trials and
      comparative studies in adult inpatients that assessed either an early warning
      system or emergency response team against any of the predefined outcome measures.
      Exclusion criteria were previous systematic reviews, non-English abstracts and
      studies incorporating paediatric data. Studies were arranged in to sections
      focusing on the following interventions: Early warning systems - Single parameter
      systems - Aggregate weighted scoring systems (AWSS) Emergency response teams -
      Medical emergency teams - Multidisciplinary outreach services . In each section
      an appraisal of the level of evidence and a recommendation has been made using
      the SIGN grading system. RESULTS: 43 studies meeting the review criteria were
      identified and included for analysis. 2 studies assessed single parameter scoring
      systems and 4 addressed aggregate weighted scoring systems. A total of 20 studies
      examined medical emergency teams and 22 studies examined multidisciplinary
      outreach teams. LIMITATIONS: The exclusion of non English studies and those
      including paediatric patients does limit the applicability of this review.
      CONCLUSIONS: Much of the available evidence is of poor quality. It is clear that
      a 'whole system' approach should be adopted and that AWSS appear to be more
      effective than single parameter systems. The response to deterioration appears
      most effective when a clinician with critical care skills leads it. The need for
      service improvement differs between health care systems.

PMID- 23962487
TI  - Regulation of deubiquitinase proteolytic activity.
AB  - Deubiquitinases (DUBs) are proteolytic enzymes whose function is to oppose the
      process of the conjugation of ubiquitin to a specific substrate. This task is
      accomplished through an enzymatic cascade involving E1, E2, and E3 enzymes, which
      collectively produce a product that is either monoubiquitinated, or
      polyubiquitinated with multiple single ubiquitins or with ubiquitin chains. The
      resulting modifications may impact protein function or may lead to the
      degradation of the ubiquitinated species, so the removal of such modifications
      must be tightly regulated. On the basis of recent work featuring crystal
      structures and detailed biochemical or biophysical studies of DUBs, we will
      discuss here how posttranslational modifications, protein binding partners, and
      reactive oxygen species regulate their catalytic activity. 

PMID- 23962486
TI  - Correlative cryo-electron tomography and optical microscopy of cells.
AB  - The biological processes occurring in a cell are complex and dynamic, and to
      achieve a comprehensive understanding of the molecular mechanisms underlying
      these processes, both temporal and spatial information is required. While cryo
      electron tomography (cryoET) provides three-dimensional (3D) still pictures of
      near-native state cells and organelles at molecular resolution, fluorescence
      light microscopy (fLM) offers movies of dynamic cellular processes in living
      cells. Combining and integrating these two commonly used imaging modalities
      (termed correlative microscopy) provides a powerful means to not only expand the
      imaging scale and resolution but also to complement the dynamic information
      available from optical microscopy with the molecular-level, 3D ultrastructure
      detail provided by cryoET. As such, a correlative approach performed on a given
      specimen can provide high resolution snapshots of dynamic cellular events. In
      this article, I review recent advances in correlative light microscopy and cryoET
      and discuss major findings made available by applying this method. 

PMID- 23962488
TI  - The contribution of mixed dishes to vegetable intake among US children and
      adolescents.
AB  - OBJECTIVE: To describe the contribution of mixed dishes to vegetable consumption
      and to estimate vegetable intake according to specific types of vegetables and
      other foods among US children and adolescents. DESIGN: The 2003-2008 National
      Health and Nutrition Examination Survey (NHANES), a nationally representative
      probability survey conducted in the USA. SETTING: Civilian non-institutionalized
      US population. SUBJECTS: All children and adolescents aged 2-18 years who met
      eligibility criteria (n 9169). RESULTS: Approximately 59 % of total vegetable
      intake came from whole forms of vegetables with 41 % coming from a mixed dish.
      White potatoes (10.7 (SE 0.6) %), fried potatoes (10.2 (SE 0.4) %), potato chips
      (8.6 (SE 0.5) %) and other vegetables (9.2 (SE 0.5) %) accounted for most
      vegetables in their whole forms, whereas pasta dishes (9.5 (SE 0.4) %),
      chilli/soups/stews (7.0 (SE 0.5) %), pizza/calzones (7.6 (SE 0.3) %) and other
      foods (13.7 (SE 0.6) %) accounted for most mixed dishes. Usual mean vegetable
      intake was 1.02 cup equivalents/d; however, after excluding vegetables from mixed
      dishes, mean intake fell to 0.54 cup equivalents/d and to 0.32 cup equivalents/d
      when fried potatoes were further excluded. CONCLUSIONS: Mixed dishes account for
      nearly half of overall vegetable intake in US children and adolescents. It is
      critical for future research to examine various components of vegetable intake
      carefully in order to inform policy and programmatic efforts aimed at improving
      dietary intake among children and adolescents.

PMID- 23962489
TI  - Non-occupational HIV post-exposure prophylaxis at a Sydney metropolitan sexual
      health clinic.
AB  - BACKGROUND: Non-occupational HIV post-exposure prophylaxis (NPEP) is prescribed
      following a risk exposure in an effort to reduce the risk of HIV seroconversion.
      We aimed to describe the prescribing practices of NPEP at RPA Sexual Health in
      Sydney, the prevalence and correlates of adverse events (AEs), and factors
      associated with completing the 28-day course. METHODS: The study population
      included individuals prescribed NPEP during January 2008-December 2011.
      Correlates of AEs and course completion were assessed by logistic regression.
      RESULTS: On 319 occasions during the study period, 282 individuals presented for
      NPEP. Over 90% of presentations followed unprotected anal intercourse between
      men, mostly receptive (63.6%). Tenofovir-emtricitabine-stavudine (n=149; 46.7%)
      and tenofovir-emtricitabine (n=136; 42.6%) were most commonly prescribed. AEs
      were reported at 101 presentations (31.7%, 95% confidence interval (CI): 26.6
      37.1%), with nausea and lethargy/malaise being the most common. Younger age (P
      for trend=0.032), earlier year of NPEP prescription (P for trend=0.011), being
      prescribed a regimen other than tenofovir-emtricitabine (P=0.026), changing the
      NPEP regimen (P<0.001) and known completion of the course (P=0.005) were
      independently associated with AEs. The course was completed in 228 presentations
      (71.5%, 95% CI: 66.2-76.4%). Completion was associated with reporting AEs
      (P=0.007) and changing regimen (P=0.001). No documented NPEP failures were
      identified, although two recipients subsequently seroconverted to HIV due to
      ongoing high-risk behaviour. CONCLUSIONS: NPEP is appropriately targeted to the
      highest risk HIV exposures at our clinic. Active recall may improve follow-up
      rates in NPEP recipients.

PMID- 23962490
TI  - Evaluating the effectiveness of an Australian obesity mass-media campaign: how
      did the 'Measure-Up' campaign measure up in New South Wales?
AB  - In 2008, the Australian Government launched a mass-media campaign 'Measure-Up' to
      reduce lifestyle-related chronic disease risk. Innovative campaign messages
      linked waist circumference and chronic disease risk. Communication channels for
      the campaign included television, press, radio and outdoor advertising and local
      community activities. This analysis examines the impact of the campaign in the
      state of New South Wales, Australia. Cross-sectional telephone surveys (n = 1006
      adults pre- and post-campaign) covered self-reported diet and physical activity,
      campaign awareness, knowledge about waist circumference, personal relevance of
      the message, perceived confidence to make lifestyle changes and waist-measuring
      behaviours. The campaign achieved high unprompted (38%) and prompted (89%)
      awareness. From pre- to post-campaign, knowledge and personal relevance of the
      link between waist circumference and chronic disease and waist measuring
      behaviour increased, although there were no significant changes in reported fruit
      and vegetable intake nor in physical activity. Knowledge of the correct waist
      measurement threshold for chronic disease risk increased over 5-fold, adjusted
      for demographic characteristics. 'Measure-Up' was successful at communicating the
      new campaign messages. Continued long-term investment in campaigns such as
      'Measure-Up', supplemented with community-based health promotion, may contribute
      to population risk factor understanding and behaviour change to reduce chronic
      disease. 

PMID- 23962491
TI  - 'Let Us Protect Our Future' a culturally congruent evidenced-based HIV/STD risk
      reduction intervention for young South African adolescents.
AB  - One of the worst HIV/AIDS epidemics in the world is occurring in South Africa,
      where heterosexual exposure is the main mode of HIV transmission. Young people 15
      24 years of age, particularly women, account for a large share of new infections.
      Accordingly, there is an urgent need for behavior-change interventions to reduce
      the incidence of HIV among adolescents in South Africa. However, there are few
      such interventions with proven efficacy for South African adolescents, especially
      young adolescents. A recent cluster-randomized controlled trial of the 'Let Us
      Protect Our Future!' HIV/STD risk-reduction intervention for Grade 6 South
      African adolescents (mean age = 12.4 years) found significant decreases in self
      reported sexual risk behaviors compared with a control intervention. This article
      describes the intervention, the use of the social cognitive theory and the
      reasoned action approach to develop the intervention, how formative research
      informed its development and the acceptability of the intervention. Challenges in
      designing and implementing HIV/STD risk-reduction interventions for young
      adolescents in sub-Saharan Africa are discussed. 

PMID- 23962492
TI  - Replicating impact of a primary school HIV prevention programme: primary school
      action for better health, Kenya.
AB  - School-based programmes to combat the spread of HIV have been demonstrated to be
      effective over the short-term when delivered on a small scale. The question
      addressed here is whether results obtained with small-scale delivery are
      replicable in large-scale roll-out. Primary School Action for Better Health
      (PSABH), a programme to train teachers to deliver HIV-prevention education in
      upper primary-school grades in Kenya demonstrated positive impact when tested in
      Nyanza Province. This article reports pre-, 10-month post- and 22-month post
      training results as PSABH was delivered in five additional regions of the
      country. A total of 26 461 students from 110 primary schools in urban and rural,
      middle- and low-income settings participated in this repeated cross-sectional
      study. Students ranged in age from 11 to 16 years, were predominantly Christian
      (10% Muslim), and the majority were from five different ethnic groups. Results
      demonstrated positive gains in knowledge, self-efficacy related to changes in
      sexual behaviours and condom use, acceptance of HIV+ students, endorsement of HIV
      testing and behaviours to post-pone sexual debut or decrease sexual activity.
      These results are as strong as or stronger than those demonstrated in the
      original impact evaluation conducted in Nyanza Province. They support the roll
      out of the programme across Kenyan primary schools. 

PMID- 23962493
TI  - Smoking cessation in groups--who benefits in the long term?
AB  - The 'Rauchfrei Programm' is the most widespread cognitive behavioral group
      program for smoking cessation in Germany. The aim of this study was to evaluate
      smoking cessation in the routine care setting and to investigate whether certain
      characteristics predict long-term abstinence. The study is a longitudinal field
      study with a one group pre-post-follow-up design. Participants were 1319 smokers,
      who were asked to complete questionnaires before and after the program. Twelve
      months later, participants were followed-up by phone. 48.1% of participants
      attended every session. At the end of the program, 60.9% of the participants were
      smoke-free. After one year, the abstinence rate accounted for 31.8% (Intention-to
      treat). A logistic regression analysis showed that male gender, higher age, being
      married, lower level of nicotine dependence as well as adherence to the program
      significantly increased the likelihood of abstinence, whereas education and
      employment did not. No significant influence of self-payment on the rates of
      abstinence was observed. It is concluded that the modern smoking cessation
      program is highly recommendable as it achieves sufficient abstinence rates in a
      real-life setting. However, it still remains a challenge to increase adherence
      rates and to achieve comparable success rates in smokers with different
      characteristics.

PMID- 23962494
TI  - Impact of erosive conditions on tooth-colored restorative materials.
AB  - OBJECTIVES: To give an overview of the impact of erosive conditions on the
      behavior of tooth-colored restoratives and performance of dental adhesives.
      METHODS: Acid-induced erosive lesions of enamel and dentin often need restorative
      procedures for rehabilitation. Nowadays, mostly tooth-colored restoratives
      (ceramics or resin composites), which are adhesively fixed to the dental
      substrate are used for this purpose. In some cases it might be necessary to seal
      the exposed dentin before achieving this goal in order to combat
      hypersensitivities and to protect those teeth from further erosive and abrasive
      loss. Moreover, it is conceivable that patients will fall back into their old
      "erosive behavior" after the application of restoratives. The following overview
      describes in how far intra-oral erosive conditions might affect the integrity of
      restorative materials, such as composite resins and ceramics, or of dentin
      sealants. Additionally, the use of erosively altered enamel and dentin as
      substrate for adhesive technologies is elucidated. RESULTS: In the literature,
      information of the behavior of tooth-colored restoratives under still persisting
      erosive conditions are limited and mostly based on in vitro-studies. There is
      information that the adhesion of dental adhesives to eroded dentin is compromised
      as compared to regular dentin. The impact of erosive conditions relevant for the
      oral cavity on ceramics and resin composites seems to be rather low, although
      only few clinical studies are available. SIGNIFICANCE: The review showed that
      erosive conditions might have only little impact on behavior of tooth-colored
      restorative materials, such as composites and ceramics. Dentin sealants also seem
      to be rather resistant against erosive conditions and might therefore serve as an
      intermediary treatment option for exposed dentin surfaces. The adhesion of dentin
      adhesives to eroded dentin might be increased by mechanical pre-treatment of the
      substrate, but needs further investigation.

PMID- 23962495
TI  - Repeat expansion in C9ORF72 is not a major cause of amyotrophic lateral sclerosis
      among Iranian patients.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in
      populations of European descent. It was recently found that a hexanucleotide
      repeat expansion in C9ORF72 is its most common cause in these populations. The
      contribution of C9ORF72 to ALS is notably lower in the Far East, but its role in
      other populations is unknown. Results of C9ORF72 screening in 78 unrelated
      Iranian ALS patients are reported here. The repeat expansion was observed in only
      1 (5.9%) of the familial and 1 (1.6%) of the sporadic cases. These figures are to
      be compared, respectively, with 30% and 6.9% among patients of European
      ethnicity. Screenings of C9ORF72 in other Middle East countries will reveal
      whether the low contribution of C9ORF72 to ALS is a feature of the entire region.
      During the screenings, it was noted that in a single family, 3 individuals
      affected with ALS, Parkinson's disease, or frontotemporal dementia all carried
      the repeat expansion. The finding suggests the mutation does rarely contribute to
      the etiology of Parkinson's disease.

PMID- 23962497
TI  - MicroRNAs in Alzheimer's disease: differential expression in hippocampus and cell
      free cerebrospinal fluid.
AB  - MicroRNAs (miRNAs) are small, noncoding RNAs that function in complex networks to
      regulate protein expression. In the brain, they are involved in development and
      synaptic plasticity. In this study, we aimed to identify miRNAs with a
      differential expression in either hippocampus or cerebrospinal fluid (CSF) from
      Alzheimer's disease (AD) patients and age-matched nondemented control subjects
      using quantitative polymerase chain reaction. In hippocampus, we also
      differentiated between AD patients with an intermediate stage, according to Braak
      III/IV stage, and a late stage, characterized according to Braak VI stage. Eight
      selected miRNAs were analyzed in hippocampus, and the expression of miR-16, miR
      34c, miR-107, miR-128a, and miR-146a were differentially regulated. In CSF, out
      of 8 selected miRNAs only miR-16 and miR-146a could be reliably detected. In
      addition, we identified an effect of blood contamination on the CSF levels of miR
      16, miR-24, and miR-146a. For group comparisons, we therefore selected CSF
      samples absent of, or containing only low numbers of blood cells. Levels of miR
      146a were significantly decreased in CSF of AD patients. In conclusion, the
      abnormal expression of several miRNAs in hippocampus of intermediate- and late
      stage AD patients suggests their involvement in AD pathogenesis, and low levels
      of miR-146a in CSF were associated with AD. 

PMID- 23962498
TI  - Synthesis, structure and urease inhibition studies of Schiff base copper(II)
      complexes with planar four-coordinate copper(II) centers.
AB  - Seven new Schiff base copper(II) complexes with planar four-coordinate copper(II)
      centers have been synthesized and structurally characterized. The solid state
      structures of complexes 1, 3, 4, 5, 6 and 7 present a square-planar coordination
      geometry at the metal centers while complex 2 shows a slightly distorted square
      planar geometry. Density functional theory calculations have been performed to
      evaluate the electronic structure of copper(II) complex 7. Inhibition of jack
      bean urease by copper(II) complexes 1-7 have also been investigated, and potent
      inhibitory activities with IC50 range of 2.60-17.00MUM have been observed for
      these mononuclear copper(II) complexes. A docking analysis using a DOCK program
      was conducted to explain the urease inhibitory activity of the copper(II)
      complexes and the structure-activity relationships were further discussed. 

PMID- 23962499
TI  - Intercalative interaction of asymmetric copper(II) complex with DNA:
      experimental, molecular docking, molecular dynamics and TDDFT studies.
AB  - The intercalative interactions of small molecules with DNA are important in a
      variety of biological processes including mutagenesis, carcinogenesis, and
      chemotherapy. A comprehensive research protocol including experiments and
      calculations was employed to investigate the intercalative interaction between
      metallointercalator copper(II) complex and DNA. The intercalative binding mode
      has been validated by UV spectra, fluorescence spectra, CD spectra and viscosity
      measurements. The classical molecular dynamics simulation was carried out to
      investigate the intercalative interaction between asymmetric copper(II) complex
      and DNA. An analytical method was proposed to simulate the dynamically changing
      absorption spectra of intercalator/DNA system. According to the established
      model, the changing process of the electronic absorption spectra for
      intercalator/DNA system can be predicted accurately. A rational explanation for
      the change law of absorption spectra has been proposed. Moreover, the analyses of
      the frontier orbital reveal that the red shift of the absorption spectra is due
      to the increase of pi orbital energy caused by the coupling of the pi orbital of
      the intercalated ligand with the pi orbital of DNA. This cause of red shift of
      spectra is completely different from the previous inference. All these insights
      are of crucial importance for correctly analyzing the absorption spectra of
      intercalative interaction, as well as for explaining the macroscopic phenomena
      observed in experiments at the molecular level. 

PMID- 23962500
TI  - Interleukin 27 could be useful in the diagnosis of tuberculous pleural effusions.
AB  - BACKGROUND: The diagnosis of tuberculous pleural effusion (TBPE) has some
      limitations. We studied the efficacy of interleukin-27 (IL-27) in the diagnosis
      of TBPE. METHODS: We measured IL-27, adenosine deaminase (ADA), ADA-2, interferon
      gamma (IFNgamma), and the ADA.IL-27 and ADA-2.IL-27 products in all the pleural
      effusion fluids. The diagnostic yield of IL-27 was evaluated with receiver
      operating characteristic curves. RESULTS: Of 431 pleural effusions, 70 were
      tuberculous, 146 were neoplastic, 58 were parapneumonic, 28 were empyemas, 88
      were transudates, and 41 were other types. With a cutoff point of 0.55 ng/mL, IL
      27 had a sensitivity of 91.4% and a specificity of 85.1%, which were
      significantly less than ADA, ADA-2, IFNgamma, ADA.IL-27, or ADA-2.IL-27. The area
      under the receiver operating characteristic curve for IL-27 (0.963) was also
      significantly lower than that for the other markers, except for IFNgamma.
      However, IL-27 improved the sensitivity of ADA and ADA-2 through ADA.IL-27 and
      ADA-2.IL-27 products (100% for both). CONCLUSIONS: IL-27 is less efficient than
      ADA and ADA-2 in the diagnosis of TBPE. However, ADA.IL-27 and ADA-2.IL-27
      improve the diagnostic sensitivity of ADA and ADA-2, and thus could be useful in
      situations of high clinical suspicion and low ADA level. A value above the cutoff
      point of the latter is practically diagnostic of TBPE.

PMID- 23962496
TI  - Protective effect of LRRK2 p.R1398H on risk of Parkinson's disease is independent
      of MAPT and SNCA variants.
AB  - The best validated susceptibility variants for Parkinson's disease are located in
      the alpha-synuclein (SNCA) and microtubule-associated protein tau (MAPT) genes.
      Recently, a protective p.N551K-R1398H-K1423K haplotype in the leucine-rich repeat
      kinase 2 (LRRK2) gene was identified, with p.R1398H appearing to be the most
      likely functional variant. To date, the consistency of the protective effect of
      LRRK2 p.R1398H across MAPT and SNCA variant genotypes has not been assessed. To
      address this, we examined 4 SNCA variants (rs181489, rs356219, rs11931074, and
      rs2583988), the MAPT H1-haplotype-defining variant rs1052553, and LRRK2 p.R1398H
      (rs7133914) in Caucasian (n = 10,322) and Asian (n = 2289) series. There was no
      evidence of an interaction of LRRK2 p.R1398H with MAPT or SNCA variants (all p >=
      0.10); the protective effect of p.R1398H was observed at similar magnitude across
      MAPT and SNCA genotypes, and the risk effects of MAPT and SNCA variants were
      observed consistently for LRRK2 p.R1398H genotypes. Our results indicate that the
      association of LRRK2 p.R1398H with Parkinson's disease is independent of SNCA and
      MAPT variants, and vice versa, in Caucasian and Asian populations.

PMID- 23962501
TI  - Pleuro-pulmonary complications of rheumatoid arthritis.

PMID- 23962502
TI  - Family reliance on physicians' decisions in life-sustaining treatments in acute
      on-chronic respiratory diseases in a respiratory ICU: a single-center study.
AB  - BACKGROUND: In ICUs, many patients are unable to participate in decision-making
      regarding life-sustaining treatments. This study evaluated the opinions of family
      members about family and physician participation in life-sustaining treatment
      decisions and examined factors that influence those decisions. METHODS: This was
      a prospective exploratory observational study that used convenience sampling.
      Inquiry interviews were conducted over a 3-year period, with 126 family members
      (out of 303 potential participants) of patients with acute-on-chronic respiratory
      failure, who had been admitted to the respiratory ICU and were dependent on
      invasive or noninvasive mechanical ventilation. Patients of <= 18 years old, with
      a stay of < 3 days, and oncologic patients were excluded. RESULTS: Ninety-eight
      percent (123/126) of the participant family members had an opinion about their
      involvement in decision-making about life-sustaining treatments. Physician choice
      was preferred by 54/123 (44%), 55/123 (45%) wished to share the decision with the
      physician, and 14/123 (11%) wished the family to decide. All the patients were
      incompetent at the time of inquiry. Autonomy prior to admission to the
      respiratory ICU influenced the decision. CONCLUSIONS: A majority of the families
      relied on physicians to help in the decision-making process about life-sustaining
      treatments in patients with acute-on-chronic respiratory diseases. From the
      family's point of view, the principle of autonomy can be exercised by delegating
      the decision-making process to the physician. To assume a uniform ethical conduct
      is to antagonize the definition of ethics.

PMID- 23962503
TI  - Apnea testing: the effects of insufflation catheter size and flow on pressure and
      volume in a test lung.
AB  - BACKGROUND: The apnea test is used to determine the absence of respiratory drive
      when determining brain death. Current guidelines for performing the apnea test do
      not specify the size of insufflation catheter (IC) to use with each endotracheal
      tube (ETT) size, despite case reports describing procedure-related complications
      with the use of various IC sizes. We studied the effect of the ratio of IC outer
      diameter to ETT inner diameter on the pressure and volume generated within the
      lungs during the apnea test. METHODS: We tested ETTs with inner diameters of 6.0
      10.0 mm, IC outer diameters of 10-16 French, and oxygen-supply tubing, at oxygen
      flows of 6-15 L/min, in an intubation manikin connected to a test lung. RESULTS:
      The multivariate analysis of variance method identified significant differences
      in the pressures and volumes during the apnea test (P < .001), and the Tukey
      method identified significant differences in the pressures and volumes associated
      with IC/ETT ratios >= 0.7 and < 0.7 (P < .05). CONCLUSIONS: An IC with an outer
      diameter < 70% of the ETT inner diameter, at 6 L/min, may prevent inappropriate
      lung pressure and volume during the apnea test. This recommendation, coupled with
      current American Academy of Neurology guidelines for the determination of brain
      death, may reduce the risk of procedure-related complications.

PMID- 23962504
TI  - Seeding experiments demonstrate poor performance of the hatching test for
      detecting small numbers of Schistosoma mansoni eggs in feces.
AB  - Parasitological methods for the evaluation of schistosomiasis tend to be limited
      when parasitic burdens are low, which is a major characteristic of low intensity
      transmission areas. While the hatching test (HT) method has been considered to be
      "very sensitive", reports of its capacity to detect low numbers of eggs remain
      scarce in the published literature. Our main hypothesis is that HT has
      limitations and cannot be recommended for diagnosing light infections or as a
      control of cure. Hence, this study aims to describe the performance of HT in
      detail, with respect to seeding experiments for egg numbers in the range of 4 to
      24 eggs per gram (epg) of feces. Different numbers of eggs of Schistosoma mansoni
      were seeded in normal human feces. The first set of experiments evaluated the
      amount of feces (higher than 0.5 g prevented hatching), the proximity of the
      light source (50 cm was preferred), and the observation time required for the
      detection of miracidia (more than 3h did not add to sensitivity). HT was
      subsequently performed with 12, 10, 8, 6, 4, and 2 eggs in 0.5 g of feces. The
      final set of experiments was performed to analyze the initial filtration step, in
      which surgical gauze versus a 500 MUm nylon mesh was compared and demonstrated
      losses of eggs that occurred with washing and gauze (better with nylon) sieving
      steps. The proposed method was found to produce 100% positivity for up to 12 epg,
      with a sharp decrease to 33% for 8 epg and less. In conclusion, HT is not
      recommended for diagnosing intestinal schistosomiasis in populations with light
      infections, considering the complexity of the procedure and its lack of
      effectiveness with fecal amounts higher than 0.5 g even at optimized conditions.

PMID- 23962505
TI  - Development of a multi-residue method for fast screening and confirmation of 20
      prohibited veterinary drugs in feedstuffs by liquid chromatography tandem mass
      spectrometry.
AB  - A simple multiresidue method was developed for detecting and quantifying twenty
      analytes from 5 classes of prohibited veterinary drugs (beta-agonists (9),
      anabolic hormones (4), quinoxalines (4), tranquilizers (1), cyproheptadine, and
      clonidine in animal feeds using a QuEChERS (Quick, Easy, Cheap, Effective, Rugged
      and Safe) approach. Feed samples were extracted by ultrasonic-assisted extraction
      with a mixture of methanol-acetonitrile (50:50, v/v), followed by a cleanup using
      a dispersive solid-phase extraction with PSA (primary secondary amine). Target
      compounds were separated and determined by a liquid chromatography tandem
      quadrupole mass spectrometer operating in positive electrospray ionization mode,
      using multiple reaction monitoring (MRM). The recoveries of these compounds were
      between 56.7% and 103% at three spiked levels. The repeatability was lower than
      10%, whereas reproducibility was no more than 15% except for nandrolone (17% at
      10MUgkg(-1)) and diazepam (19% at 10MUgkg(-1)). Decision limits (CCalphas) and
      detection capabilities (CCbetas) ranged from 0.42 to 5.74MUgkg(-1) and 5.70
      9.81MUgkg(-1), respectively. The method was successfully applied to screening of
      real samples obtained from local feed markets and confirmation of the suspected
      target analytes. 

PMID- 23962506
TI  - Advancing comparative studies of patterns of care and economic outcomes in
      cancer: challenges and opportunities.

PMID- 23962507
TI  - Health systems performance and cancer outcomes.
AB  - Do the characteristics of health systems influence cancer outcomes? Although
      caveats are required when undertaking international comparisons of both health
      systems and cancer outcomes, observed differences cannot solely be explained by
      data problems or economic development. Health systems can influence cancer
      outcomes through three mechanisms: coverage, innovation, and quality of care.
      First, in countries where population coverage is incomplete, patients may find
      certain services excluded or face substantial copayments or deductibles. Second,
      there are variations in the rate at which innovative treatments are introduced,
      reflecting in particular the need for publicly funded health systems to compare
      costs and benefits of increasingly expensive treatments given demands for other
      treatments. Third, systematic differences in quality of care (early diagnosis,
      timely and equitable access to specialist care, and existence of systematic
      coordination between these activities) may lead to variations in cancer outcomes.

PMID- 23962508
TI  - Patterns of colorectal cancer care in the United States and Canada: a systematic
      review.
AB  - Colorectal cancer is the third most common cancer in the United States and
      Canada. Given the high incidence and increased survival of colorectal cancer
      patients, prevalence is increasing over time in both countries. Using MEDLINE, we
      conducted a systematic review of the literature published between 2000 and 2010
      to describe patterns of colorectal cancer care. Specifically we examined data
      sources used to obtain treatment information and compared patterns of cancer
      directed initial care, post-diagnostic surveillance care, and end-of-life care
      among colorectal cancer patients diagnosed in the United States and Canada.
      Receipt of initial treatment for colorectal cancer was associated with the
      anatomical position of the tumor and extent of disease at diagnosis, in
      accordance with consensus-based guidelines. Overall, care trends were similar
      between the United States and Canada; however, we observed differences with
      respect to data sources used to measure treatment receipt. Differences were also
      present between study populations within country, further limiting direct
      comparisons. Findings from this review will allow researchers, clinicians, and
      policy makers to evaluate treatment receipt by patient, clinical, or system
      characteristics and identify emerging trends over time. Furthermore, comparisons
      between health-care systems in the United States and Canada can identify
      disparities in care, allow the evaluation of different models of care, and
      highlight issues regarding the utility of existing data sources to estimate
      national patterns of care. 

PMID- 23962509
TI  - Patterns of colorectal cancer care in Europe, Australia, and New Zealand.
AB  - Colorectal cancer is the second most common cancer in women and the third most
      common in men worldwide. In this study, we used MEDLINE to conduct a systematic
      review of existing literature published in English between 2000 and 2010 on
      patterns of colorectal cancer care. Specifically, this review examined 66 studies
      conducted in Europe, Australia, and New Zealand to assess patterns of initial
      care, post-diagnostic surveillance, and end-of-life care for colorectal cancer.
      The majority of studies in this review reported rates of initial care, and
      limited research examined either post-diagnostic surveillance or end-of-life care
      for colorectal cancer. Older colorectal cancer patients and individuals with
      comorbidities generally received less surgery, chemotherapy, or radiotherapy.
      Patients with lower socioeconomic status were less likely to receive treatment,
      and variations in patterns of care were observed by patient demographic and
      clinical characteristics, geographical location, and hospital setting. However,
      there was wide variability in data collection and measures, health-care systems,
      patient populations, and population representativeness, making direct comparisons
      challenging. Future research and policy efforts should emphasize increased
      comparability of data systems, promote data standardization, and encourage
      collaboration between and within European cancer registries and administrative
      databases. 

PMID- 23962511
TI  - Variations in cancer survival and patterns of care across Europe: roles of wealth
      and health-care organization.
AB  - Cancer survival varies markedly across Europe. We analyzed variations in all
      cancer 5-year relative survival in relation to macroeconomic and health-care
      indicators, and 5-year relative survival for three major cancers (colorectal,
      prostate, breast) in relation to application of standard treatments, to serve as
      baseline for monitoring the efficacy of new European initiatives to improve
      cancer survival. Five-year relative survival data were from the European cancer
      registry-based study of cancer patients' survival and care (EUROCARE-4).
      Macroeconomic and health system data were from the Organisation for Economic Co
      operation and Development, and European Observatory on Health Care Systems.
      Information on treatments given was from EUROCARE studies. Total national health
      spending varied widely across Europe and correlated linearly with survival (R =
      0.8). Countries with high spending had high numbers of diagnostic and
      radiotherapy units, and 5-year relative survival was good (>50%). The treatments
      given for major cancers also varied; advanced stage at diagnosis was associated
      with poor 5-year relative survival and low odds of receiving standard treatment
      for breast and colorectal cancer. 

PMID- 23962510
TI  - Economic studies in colorectal cancer: challenges in measuring and comparing
      costs.
AB  - Estimates of the costs associated with cancer care are essential both for
      assessing burden of disease at the population level and for conducting economic
      evaluations of interventions to prevent, detect, or treat cancer. Comparisons of
      cancer costs between health systems and across countries can improve
      understanding of the economic consequences of different health-care policies and
      programs. We conducted a structured review of the published literature on
      colorectal cancer (CRC) costs, including direct medical, direct nonmedical (ie,
      patient and caregiver time, travel), and productivity losses. We used MEDLINE to
      identify English language articles published between 2000 and 2010 and found 55
      studies. The majority were conducted in the United States (52.7%), followed by
      France (12.7%), Canada (10.9%), the United Kingdom (9.1%), and other countries
      (9.1%). Almost 90% of studies estimated direct medical costs, but few studies
      estimated patient or caregiver time costs or productivity losses associated with
      CRC. Within a country, we found significant heterogeneity across the studies in
      populations examined, health-care delivery settings, methods for identifying
      incident and prevalent patients, types of medical services included, and
      analyses. Consequently, findings from studies with seemingly the same objective
      (eg, costs of chemotherapy in year following CRC diagnosis) are difficult to
      compare. Across countries, aggregate and patient-level estimates vary in so many
      respects that they are almost impossible to compare. Our findings suggest that
      valid cost comparisons should be based on studies with explicit standardization
      of populations, services, measures of costs, and methods with the goal of
      comparability within or between health systems or countries. Expected increases
      in CRC prevalence and costs in the future highlight the importance of such
      studies for informing health-care policy and program planning. 

PMID- 23962512
TI  - Initial treatment for newly diagnosed elderly colorectal cancer patients:
      patterns of care in Italy and the United States.
AB  - Cancer is a major component of health-care expenditures in most developed
      countries. The costs of cancer care are expected to increase due to rising
      incidence (as the population ages) and increasing use of targeted anticancer
      therapies. However, epidemiological analysis of patterns of care may be required
      prior to empirically well-grounded cost analyses. Additionally, comparisons of
      care between health-care delivery systems and countries can identify
      opportunities to improve practice. They can also increase understanding of
      patient outcomes and economic consequences of differences in policies related to
      cancer screening, treatment, and programs of care. In this study, we compared
      patterns of colorectal cancer treatment during the first year following diagnosis
      in two cohorts of elderly patients from some areas of Italy and the United States
      using cancer registry linked to administrative data. We evaluated hospital use,
      initial treatments (surgery, chemotherapy, and radiation), and timeliness of
      surgery and adjuvant therapy, taking into account patient characteristics and
      clinical features, such as stage at diagnosis and the cancer subsite. We observed
      greater use of adjuvant chemotherapy in stage III and IV colon cancer patients
      and adjuvant therapy in all stages of rectal cancer patients in the US cohort. We
      found a higher rate of open surgeries in the Italian cohort, a similar rate of
      hospitalization, but a higher number of hospital days in the Italian cohort.
      However, in spite of structural differences between the United States and Italy
      in health-care organization and delivery as well as in data collection, patterns
      of care and the timing of care in the year after diagnosis are generally similar
      among patients within stage of disease at diagnosis. Comparative studies of the
      costs associated with patterns of cancer care will be important for future
      research. 

PMID- 23962513
TI  - The challenge of conducting comparative effectiveness research in cancer: the
      impact of a fragmented U.S. health-care system.
AB  - Comparative effectiveness research (CER) can make important contributions to the
      transformation of US health care by filling gaps left by tightly controlled
      clinical trials. However, without comprehensive and comparable data that reflect
      the diversity of the US health-care system, CER's value will be diminished. We
      document the limits of observational CER by examining the age at diagnosis,
      disease stage, and select measures of health-care use among individuals diagnosed
      with incident cancer aged 65 or older from four large health maintenance
      organizations (HMOs) relative to seniors identified through the linked
      Surveillance, Epidemiology, and End Results (SEER)-Medicare data for the period
      1999-2007. Aged individuals in the HMOs were younger, diagnosed at earlier
      stages, and more likely to receive care in inpatient settings than individuals in
      the linked SEER-Medicare data. These differences highlight the need for
      comprehensive and comparable datasets that reflect the diversity of US health
      care to support CER that can inform health-care reform in the United States. 

PMID- 23962514
TI  - A standardized relative resource cost model for medical care: application to
      cancer control programs.
AB  - Medicare data represent 75% of aged and permanently disabled Medicare
      beneficiaries enrolled in the fee-for-service (FFS) indemnity option, but the
      data omit 25% of beneficiaries enrolled in Medicare Advantage health maintenance
      organizations (HMOs). Little research has examined how longitudinal patterns of
      utilization differ between HMOs and FFS. The Burden of Cancer Study developed and
      implemented an algorithm to assign standardized relative costs to HMO and
      Medicare FFS data consistently across time and place. Medicare uses 15 payment
      systems to reimburse FFS providers for covered services. The standardized
      relative resource cost algorithm (SRRCA) adapts these various payment systems to
      utilization data. We describe the rationale for modifications to the Medicare
      payment systems and discuss the implications of these modifications. We applied
      the SRRCA to data from four HMO sites and the linked Surveillance, Epidemiology,
      and End Results-Medicare data. Some modifications to Medicare payment systems
      were required, because data elements needed to categorize utilization were
      missing from both data sources. For example, data were not available to create
      episodes for home health services received, so we assigned costs per visit based
      on visit type (nurse, therapist, and aide). For inpatient utilization, we
      modified Medicare's payment algorithm by changing it from a flat payment per
      diagnosis-related group to daily rates for diagnosis-related groups to
      differentiate shorter versus longer stays. The SRRCA can be used in multiple
      managed care plans and across multiple FFS delivery systems within the United
      States to create consistent relative cost data for economic analyses. Prior to
      international use of the SRRCA, data need to be standardized. 

PMID- 23962515
TI  - Evaluation of new technologies for cancer control based on population trends in
      disease incidence and mortality.
AB  - Cancer interventions often disseminate in the population before evidence of their
      effectiveness is available. Population disease trends provide a natural
      experiment for assessing the characteristics of the disease and the potential
      impact of the intervention. We review models for extracting information from
      population data for use in economic evaluations of cancer screening
      interventions. We focus particularly on prostate-specific antigen (PSA) screening
      for prostate cancer and describe approaches that can be used to project the
      likely costs and benefits of competing screening policies. Results indicate that
      the lifetime probability of biopsy-detectable prostate cancer is 33%, the chance
      of clinical diagnosis without screening is 13%, and the average time from onset
      to clinical diagnosis is 14 years. Less aggressive screening policies that screen
      less often and use more conservative criteria (e.g., higher PSA thresholds) for
      biopsy referral may dramatically reduce PSA screening costs with modest impact on
      benefit. 

PMID- 23962520
TI  - Autophosphorylation of gatekeeper tyrosine by symbiosis receptor kinase.
AB  - Plant receptor-like kinases (RLKs) share their evolutionary origin with animal
      interleukin-1 receptor-associated kinase (IRAK)/Pelle family of soluble kinases
      and are distinguished by having tyrosine as 'gatekeeper'. This position is
      adjacent to the hinge region and is hidden in a hydrophobic pocket of the
      catalytic cleft of protein kinases and is therefore least probable to be a target
      for any modification. This communication illustrates the accessibility of the
      gatekeeper site (Y670) towards both autophosphorylation and dephosphorylation in
      the recombinant cytoplasmic domain of symbiosis receptor kinase from Arachis
      hypogaea (AhSYMRK). Autophosphorylation on gatekeeper tyrosine was detected prior
      to extraction but never under in vitro conditions. We hypothesize gatekeeper
      phosphorylation to be associated with synthesis/maturation of AhSYMRK and this
      phenomenon may be prevalent among RLKs. 

PMID- 23962516
TI  - Comparing cancer care, outcomes, and costs across health systems: charting the
      course.

PMID- 23962521
TI  - Pathology of bilateral pulvinar degeneration following long duration status
      epilepticus.
AB  - PURPOSE: To define the neuropathological findings of pulvinar degeneration seen
      in long duration status epilepticus. METHODS: We review the clinical, radiologic,
      neurophysiologic, investigational and neuropathological findings on a 27 year old
      woman who died after 162 days of prolonged refractory status epilepticus.
      RESULTS: Continuous EEG monitoring confirmed recurrent uncontrolled seizure
      activity bilaterally and independently, most frequent in the right fronto
      temporal region. Initial MRI of the brain was normal. Repeat study until on day
      127 of admission showed advanced changes, with bilateral pulvinar T2/FLAIR
      hyperintensities. The autopsy revealed sharply defined, grey, soft, granular
      nodules in each medial pulvinar nucleus. Microscopically these consisted of
      sharply defined paucicellular areas with loss of neurons and myelin and with
      numerous macrophages in their centers, surrounded by reactive astrocytes with
      relatively spared of axons. The spinal cord at cervical and thoracic levels
      showed symmetric spongy vacuolation in the central part of the dorsal columns and
      lateral corticospinal tracts, with mild myelin loss, relatively preserved axons.
      The pathological lesions found in this case in thepulvinar are somewhat similar
      to the pathologic lesions described in Wernicke's encephalopathy. Those found in
      the spinal cord of our patient resemble characteristic features of B12 related
      subacute combined degeneration. CONCLUSION: Characteristic pulvinar degeneration
      may be found as an acquired phenomenon in prolonged refractory status
      epilepticus. We hypothesize that the neuropathological findings result from an
      excessive focal metabolic demand, secondary to neuronal network over activation
      in the setting of prolonged, frequent bi-temporal seizures.

PMID- 23962522
TI  - Eye closure sensitivity in juvenile myoclonic epilepsy and its effect on
      prognosis.
AB  - PURPOSE: To investigate eye closure sensitivity (ECS) in the EEGs of patients
      diagnosed with juvenile myoclonic epilepsy (JME) and its relationship to
      prognosis. METHODS: We included 76 JME patients with a minimum follow-up of one
      year and evaluated a total of 254 EEGs to obtain evidence of ECS. The patients
      were grouped according to their response to treatment, and these subgroups were
      compared in relation to ECS and other clinical and EEG features. RESULTS: There
      were 12 patients (15.8%) with poor prognosis who showed resistance to appropriate
      anti-epileptic drug treatment, 15 (19.7%) patients with pseudo-resistance, and 49
      (64.5%) patients with good prognosis. The EEGs of only four of the patients
      displayed pure ECS (5.3%), and only one of these exhibited poor prognosis.
      Furthermore, 11 patients (14.5%) had both ECS and photosensitivity, and two of
      these patients exhibited poor prognosis. Thus, neither pure ECS nor ECS with
      photosensitivity correlated with poor prognosis. A family history of epilepsy and
      focal findings on the EEG was correlated with poorer prognosis. CONCLUSIONS: ECS
      is a rare EEG finding in JME and does not appear to be a marker for poor
      prognosis.

PMID- 23962523
TI  - Sudden unexpected death in epilepsy (SUDEP): development of a safety checklist.
AB  - PURPOSE: The incidence of sudden death appears to be 20 times higher in patients
      with epilepsy compared with the general population. Epilepsy-related death,
      particularly sudden unexpected death in epilepsy (SUDEP), is still underestimated
      by healthcare professionals and this may reflect the mistaken belief that
      epilepsy is a benign condition. The risk of death associated with epilepsy
      appeared rarely to have been discussed with patients or their families. It
      appears the decision to discuss SUDEP and also to peg SUDEP risk is arbitrary and
      clinical. Unfortunately there is no structured evidenced mechanism at present to
      represent person centered risk of SUDEP and there is currently no easy manner or
      template to have this discussion with the family and the patient. METHODS: We
      conducted a detailed literature review in Medline, Embase and Psychinfo databases
      to extract the common risk factors as evidenced from literature till date.
      Research into risk factors has identified a number of risk factors for SUDEP,
      some of which are potentially modifiable. RESULTS: Based on the literature
      review, we believe that the ascertained risk factors could be employed in
      clinical practice as a checklist to reduce an individual patient's risk of SUDEP.
      The SUDEP safety checklist may be of practical use in reducing risks in some
      individuals and is definitely of use in helping communication. CONCLUSIONS: An
      evidence based checklist identifying the major risk factors can help both
      clinicians and patients to focus on minimizing certain risk factors and promote
      safety by focusing on the modifiable factors and guide treatment. It can be a
      tool to open a person centered discussion with patients and to outline how
      individual behaviors could impact on risk.

PMID- 23962524
TI  - Social position and frailty.
AB  - This study sought to determine (1) if measures of social position are associated
      with frailty; (2) if any observed association between social position and frailty
      is a threshold or gradient effect; and (3) if any observed association is
      independent of possible confounders. Data were drawn from a sample of 1,751
      community-dwelling adults, aged 65 and older, living in the Canadian province of
      Manitoba in 1991. Education, self-reported income adequacy, and self-reported
      income satisfaction were used as measures of social position. Frailty was graded
      based on functional loss, cognition, and urinary incontinence. Multivariate
      regression analyses revealed, after adjusting for possible confounding factors,
      that all measures of social position were strongly associated with frailty in a
      gradient, rather than a threshold, manner. We conclude that social gradients for
      frailty are present in older adults, although a causal mechanism is not yet
      clear.

PMID- 23962525
TI  - Vision-based method for tracking meat cuts in slaughterhouses.
AB  - Meat traceability is important for linking process and quality parameters from
      the individual meat cuts back to the production data from the farmer that
      produced the animal. Current tracking systems rely on physical tagging, which is
      too intrusive for individual meat cuts in a slaughterhouse environment. In this
      article, we demonstrate a computer vision system for recognizing meat cuts at
      different points along a slaughterhouse production line. More specifically, we
      show that 211 pig loins can be identified correctly between two photo sessions.
      The pig loins undergo various perturbation scenarios (hanging, rough treatment
      and incorrect trimming) and our method is able to handle these perturbations
      gracefully. This study shows that the suggested vision-based approach to tracking
      is a promising alternative to the more intrusive methods currently available. 

PMID- 23962526
TI  - Development of a novel device for applying uniform doses of electron beam
      irradiation on carcasses.
AB  - The Maxim's Electron Scatter Chamber (Maxim Chamber) was developed to obtain
      uniform dose distribution when applying electron beam (e-beam) irradiation to
      materials of irregular surface. This was achieved by placing a stainless steel
      mesh surrounding a cylindrical area where the target sample was placed. Upon
      contact with the mesh, electrons scatter and are directed onto the target from
      multiple angles, eliminating the e-beam linearity and resulting in a uniform dose
      distribution over the target surface. The effect of irradiation in the Maxim
      Chamber on dose distribution and pathogen reduction was tested on rabbit
      carcasses to simulate other larger carcasses. The dose uniformity ratio (DUR) on
      the rabbit carcasses was 1.8, indicating an acceptable dose distribution. On
      inoculated carcasses, this treatment reduced Escherichia coli O157:H7 by >5 log
      cycles. These results indicate that carcass irradiation using e-beam is feasible
      using the Maxim's electron scattering chamber. Appropriate adjustments will be
      further needed for commercial application on beef and other animal carcasses. 

PMID- 23962527
TI  - What have we learned from finite element model studies of lumbar intervertebral
      discs in the past four decades?
AB  - Finite element analysis is a powerful tool routinely used to study complex
      biological systems. For the last four decades, the lumbar intervertebral disc has
      been the focus of many such investigations. To understand the disc functional
      biomechanics, a precise knowledge of the disc mechanical, structural and
      biochemical environments at the microscopic and macroscopic levels is essential.
      In response to this need, finite element model studies have proven themselves as
      reliable and robust tools when combined with in vitro and in vivo measurements.
      This paper aims to review and discuss some salient findings of reported finite
      element simulations of lumbar intervertebral discs with special focus on their
      relevance and implications in disc functional biomechanics. Towards this goal,
      the earlier investigations are presented, discussed and summarized separately in
      three distinct groups of elastic, multi-phasic transient and transport model
      studies. The disc overall response as well as the relative role of its
      constituents are markedly influenced by loading rate, magnitude,
      combinations/preloads and posture. The nucleus fluid content and pressurizing
      capacity affect the disc compliance, annulus strains and failure sites/modes.
      Biodynamics of the disc is affected by not only the excitation characteristics
      but also preloads, existing mass and nucleus condition. The role of fluid
      pressurization and collagen fiber stiffening diminish with time during diurnal
      loading. The endplates permeability influences the time-dependent response of the
      disc in both loaded and unloaded recovery phases. The transport of solutes is
      substantially influenced by the disc size, tissue diffusivity and endplates
      permeability. 

PMID- 23962528
TI  - Prediction of ground reaction forces during gait based on kinematics and a neural
      network model.
AB  - Kinetic information during human gait can be estimated with inverse dynamics,
      which is based on anthropometric, kinematic, and ground reaction data. While
      collecting ground reaction data with a force plate is useful, it is costly and
      requires regulated space. The goal of this study was to propose a new, accurate
      methodology for predicting ground reaction forces (GRFs) during level walking
      without the help of a force plate. To predict GRFs without a force plate, the
      traditional method of Newtonian mechanics was used for the single support phase.
      In addition, an artificial neural network (ANN) model was applied for the double
      support phase to solve statically indeterminate structure problems. The input
      variables of the ANN model, which were selected to have both dependency and
      independency, were limited to the trajectory, velocity, and acceleration of the
      whole segment's mass centre to minimise errors. The predicted GRFs were validated
      with actual GRFs through a ten-fold cross-validation method, and the correlation
      coefficients (R) for the ground forces were 0.918 in the medial-lateral axis,
      0.985 in the anterior-posterior axis, and 0.991 in the vertical axis during gait.
      The ground moments were 0.987 in the sagittal plane, 0.841 in the frontal plane,
      and 0.868 in the transverse plane during gait. The high correlation
      coefficients(R) are due to the improvement of the prediction rate in the double
      support phase. This study also proved the possibility of calculating joint forces
      and moments based on the GRFs predicted with the proposed new hybrid method. Data
      generated with the proposed method may thus be used instead of raw GRF data in
      gait analysis and in calculating joint dynamic data using inverse dynamics. 

PMID- 23962529
TI  - A fluid-structure interaction study using patient-specific ruptured and
      unruptured aneurysm: the effect of aneurysm morphology, hypertension and
      elasticity.
AB  - Fluid-structure interaction (FSI) simulations using five patient-specific
      aneurysm geometries are carried out to investigate the difference between
      ruptured and unruptured aneurysms. Two different blood pressure conditions
      (normal and hypertension, for all cases), and two different values of elastic
      modulus (1 and 2MPa, for two cases) are tested. Ruptured aneurysms (RA) generally
      displayed larger displacement at the dome, lower area-average WSS and higher von
      Mises stress than unruptured aneurysms (URA) regardless of elasticity or blood
      pressure condition. RAs had a longitudinal expansion whereas URAs had a radial
      expansion, which was the key difference between the two types. The difference in
      expansion pattern may be one of the keys to explaining aneurysm rupture, and
      further analysis is required in the future to confirm this theory. 

PMID- 23962530
TI  - Factors predictive of the perceived osteoporosis-fracture link in fragility
      fracture patients.
AB  - OBJECTIVE: Given the asymptomatic nature of osteoporosis, a fragility fracture
      provides an opportunity to make the issue of osteoporosis relevant to patients.
      Patients who link their fragility fracture with osteoporosis are more likely to
      initiate osteoporosis treatment, yet to date, we know little about who is likely
      to make this link. This study examined whether demographic, health, and
      osteoporosis belief factors predicted a perceived link between a fragility
      fracture and osteoporosis. STUDY DESIGN: This longitudinal cohort study analyzed
      baseline and follow up data collected as part of a provincial osteoporosis
      screening initiative targeting fragility fracture patients. Logistic regression
      analysis was used to examine the relationship between hypothesized predictors and
      the outcome. MAIN OUTCOME MEASURE: Patient perception of the osteoporosis
      fracture link at follow up. RESULTS: At baseline, 93% (1615/1735) of patients did
      not believe their fracture could have been caused by osteoporosis. Of these, only
      8.2% changed this perception at follow up. Adjusted analyses showed that baseline
      characteristics associated with making the osteoporosis-fracture link at follow
      up were: a previous fracture (odds ratio (OR) 1.7, confidence interval (CI) 1.2
      2.6), perception of osteoporosis pharmacotherapy benefits OR 1.2 (CI 1.0-1.5),
      diagnosis of rheumatoid arthritis OR 2.6 (CI 1.4-4.9) and the perception of bones
      as "thin" OR 8.2 (CI 5.1-13.1). CONCLUSION: These results shed more light on
      patient-level barriers to osteoporosis management following an osteoporosis
      educational programme. They may be used to identify patients less likely to make
      the link between their fracture and osteoporosis and to inform interventions for
      this patient group.

PMID- 23962531
TI  - Cardiovascular responses of the anterior claustrum; its mechanism; contribution
      of medial prefrontal cortex.
AB  - The anterior claustrum (CLa) has bilateral connections with the areas involved in
      cardiovascular regulation, though its role in cardiovascular control is not yet
      understood. This study was performed to find the cardiovascular responsive region
      of the CLa by stimulating all parts of the CLa with l-glutamate, and to find the
      possible mechanisms mediating its responses in urethane-anesthetized rats. We
      also investigated the possible involvement of the medial prefrontal cortex in the
      cardiovascular responses of the CLa. The effect of microinjection of l-glutamate
      (50-100 nl, 0.25 M) was tested throughout the Cla and only in one area at 2.7 mm
      rostral to bregma, 1.8-2.0 midline and 4.5-5.6mm vertical, significant decreases
      in arterial pressure were elicited (-21.71+/-2.1 mmHg, P<0.001, t-test) with no
      significant change in heart rate. Administration (i.v.) of the muscarinic
      receptor blocker, atropine, had no effect on the change in mean arterial pressure
      in response to glutamate stimulation, suggesting that the parasympathetic system
      was not involved in this response. However, administration (i.v.) of the
      nicotinic receptor blocker, hexamethonium dichloride abolished the depressor
      response to glutamate, suggesting that CLa stimulation decreases sympathetic
      outflow to the cardiovascular system. In addition, microinjection of the
      reversible synaptic blocker, cobalt chloride, into the medial prefrontal cortex
      greatly attenuated the depressor response elicited by microinjection of glut into
      the CLa. Thus for the first time, we found the cardiovascular responsive region
      of the anterior claustrum. Also we showed that its response is mediated through
      the medial prefrontal cortex.

PMID- 23962532
TI  - Is there a lack of information on HPV vaccination given by health professionals
      to young women?
AB  - OBJECTIVE: The aim of this survey is to compare the main sources of information
      about vaccination against Human papillomavirus (HPV) of young women aged over-18
      and under-18 years. METHODS: A multicenter study was carried out in Italy through
      the administration of a questionnaire. Univariate analyses were conducted to
      evaluate possible differences between age groups and different locations (chi
      square test and Fisher test where possible). RESULTS: The sample consisted of 987
      young women. The main sources of information about HPV vaccination are
      represented by magazines/books (23.1%) and TV (20.5%) for the over-18s, while for
      the under-18s the sources are general practitioners (22.6%) and pediatricians
      (15.4%). The over-18s with health professionals as parents consult mostly
      gynecologists (27.7%) and general practitioners (20.5%). DISCUSSION: This study
      highlights lack of information on HPV vaccination given by health professionals
      to young women and underlines the need to improve education about cervical
      cancer, prevention and HPV vaccination.

PMID- 23962533
TI  - Reply to: Introducing vaccination against serogroup B meningococcal disease: An
      economic and mathematical modelling study of potential impact.

PMID- 23962534
TI  - Towards rationale vaccine policy: a case against inclusion of rabies vaccine into
      routine national immunization programme in India.

PMID- 23962536
TI  - EuSANH workshop "Reasons behind the differences in national vaccination schedules
      for under-five", European Public Health pre-conference workshop, Malta, 8
      November 2012.
AB  - Vaccination schedules for under-five children in the EU member states differ
      markedly, mainly as a consequence of differences in programme organization,
      decision making and history, and to a limited extent by epidemiological
      differences. There is little willingness towards unification since little
      evidence exists to prefer one schedule over the others, but the differences might
      impact on public confidence. Monitoring key determinants influencing individual
      decision making on immunization ('soft impacts') is thus as important as other
      existing monitoring systems of the 'hard' impacts of immunization programmes, and
      both should focus on the impact of these schedule differences. Harmonization of
      vaccination schedules is not the main issue, but the reasons behind the
      differences should be explained in an understandable and coherent way to the
      public. Scientists and advisory bodies should look over the country borders and
      communicate any crucial information, in order to improve scientific consensus on
      immunization schedules and programmes. These were the main conclusions of a
      members' experts panel of the European network of independent science advisory
      bodies on health (EuSANH), at a workshop in November 2012. 

PMID- 23962535
TI  - Effect of abatacept on immunogenicity of vaccines in individuals with type 1
      diabetes.
AB  - Abatacept delayed progression of type 1 diabetes (T1D) when administered soon
      after diagnosis. Its use in T1D is expanding to prevention trials and, therefore,
      it is important to fully characterize its immunosuppressive effect. We compared
      antibody responses to trivalent inactivated influenza vaccine (TIIV) administered
      during 2 consecutive seasons and to tetanus toxoid (TT) vaccine administered
      after 24 months of treatment in115 early onset T1D subjects randomly assigned to
      24 months of abatacept (N=71) or placebo (N=34). Anti-influenza titers before
      TIIV were similar between the 2 treatment groups and both groups had significant
      increases after vaccination. Although the magnitude of antibody responses against
      some influenza serotypes was significantly lower (p<0.05) in abatacept compared
      with placebo recipients, no differences were observed in the proportion of
      subjects with protective titers against influenza after vaccination. The
      magnitude of antibody responses against TT also tended to be lower (p=0.06) in
      abatacept compared with placebo recipients, without affecting the proportion of
      subjects who achieved protective titers. We conclude that abatacept moderately
      decreases the magnitude of antibody responses to recall vaccination. Further
      studies are needed to assess its effect on primary immunization. 

PMID- 23962537
TI  - WITHDRAWN: Immunogenicity and safety of HCV E1E2 peptide vaccine in chronically
      HCV-infected patients who did not respond to interferon based therapy.
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- 23962538
TI  - Temperature modulates the response of the thermophilous sea urchin Arbacia lixula
      early life stages to CO2-driven acidification.
AB  - The increasing abundances of the thermophilous black sea urchin Arbacia lixula in
      the Mediterranean Sea are attributed to the Western Mediterranean warming.
      However, few data are available on the potential impact of this warming on A.
      lixula in combination with other global stressors such as ocean acidification.
      The aim of this study is to investigate the interactive effects of increased
      temperature and of decreased pH on fertilization and early development of A.
      lixula. This was tested using a fully crossed design with four temperatures (20,
      24, 26 and 27  degrees C) and two pH levels (pHNBS 8.2 and 7.9). Temperature and
      pH had no significant effect on fertilization and larval survival (2d) for
      temperature <27  degrees C. At 27  degrees C, the fertilization success was very
      low (<1%) and all larvae died within 2d. Both temperature and pH had effects on
      the developmental dynamics. Temperature appeared to modulate the impact of
      decreasing pH on the % of larvae reaching the pluteus stage leading to a positive
      effect (faster growth compared to pH 8.2) of low pH at 20  degrees C, a neutral
      effect at 24  degrees C and a negative effect (slower growth) at 26  degrees C.
      These results highlight the importance of considering a range of temperatures
      covering today and the future environmental variability in any experiment aiming
      at studying the impact of ocean acidification. 

PMID- 23962539
TI  - Elastic fibres in health and disease.
AB  - Elastic fibres are insoluble components of the extracellular matrix of dynamic
      connective tissues such as skin, arteries, lungs and ligaments. They are laid
      down during development, and comprise a cross-linked elastin core within a
      template of fibrillin-based microfibrils. Their function is to endow tissues with
      the property of elastic recoil, and they also regulate the bioavailability of
      transforming growth factor beta. Severe heritable elastic fibre diseases are
      caused by mutations in elastic fibre components; for example, mutations in
      elastin cause supravalvular aortic stenosis and autosomal dominant cutis laxa,
      mutations in fibrillin-1 cause Marfan syndrome and Weill-Marchesani syndrome, and
      mutations in fibulins-4 and -5 cause autosomal recessive cutis laxa. Acquired
      elastic fibre defects include dermal elastosis, whereas inflammatory damage to
      fibres contributes to pathologies such as pulmonary emphysema and vascular
      disease. This review outlines the latest understanding of the composition and
      assembly of elastic fibres, and describes elastic fibre diseases and current
      therapeutic approaches. 

PMID- 23962540
TI  - Are Australian sexual health clinics attracting priority populations?
AB  - To answer a key question ('Are Australian sexual health clinics attracting
      priority populations?'), we used data from 44 Australian sexual health clinics
      between 2004 and 2011. We assessed the proportion of patients that were from
      priority populations (deemed to be at risk of sexually transmissible infections)
      and compared this to their proportions in the general population using data from
      Australian Bureau of Statistics and the Australian Study of Health and
      Relationships. A chi(2)-test was used. A total of 278154 new patients attended
      during 2004-2011. The proportions from each priority population were
      significantly higher (P<0.01 for all) than for the general population: young
      people aged 15-29 years (58.1% v. 20.1%), men who have sex with men (26.0% v.
      6.0%), female sex workers (10.8% v. 0.5%), and Aboriginal and Torres Strait
      Islander people (4.2% v. 2.3%). This study confirms that Australian sexual health
      clinics attract higher proportions of priority populations and are thus meeting
      their mandate as defined in the 2010-2013 National Sexually Transmissible
      Infections Strategy. 

PMID- 23962541
TI  - The science of health communication: impressions from the International
      Conference on Communication in Healthcare in St Andrews, Scotland, UK.

PMID- 23962542
TI  - Infant interest in their mother's face is associated with maternal psychological
      health.
AB  - Early experience can alter infants' interest in faces in their environment. This
      study investigated the relationship between maternal psychological health, mother
      infant bonding, and infant face interest in a community sample. A visual
      habituation paradigm was used to independently assess 3.5-month old infants'
      attention to a photograph of their mother's face and a stranger's face. In this
      sample of 54 healthy mother-infant pairs, 57% of mothers (N = 31) reported
      symptoms of at least one of stress response to trauma, anxiety, or depression.
      Interest in the mother-face, but not stranger-face, was positively associated
      with the mother's psychological health. In regression analyses, anxiety and
      depression predicted 9% of the variance in looking to the mother-face. Anxiety
      was the only significant predictor within the model. No direct associations were
      found between mother-infant bonding and infants' face interest. Taken together,
      these findings indicate that infant's visual engagement with their mother's face
      varies with maternal symptoms of emotional distress, even within a community
      sample.

PMID- 23962544
TI  - An esophageal collision tumor.

PMID- 23962543
TI  - Mother-infant interaction improves with a developmental intervention for mother
      preterm infant dyads.
AB  - While premature infants have a high need for positive interactions, both infants
      and their mothers are challenged by the infant's biological immaturity. This
      randomized clinical trial of 198 premature infants born at 29-34 weeks gestation
      and their mothers examined the impact of the H-HOPE (Hospital to Home: Optimizing
      the Infant's Environment) intervention on mother-premature infant interaction
      patterns at 6-weeks corrected age (CA). Mothers had at least 2 social
      environmental risk factors such as minority status or less than high school
      education. Mother-infant dyads were randomly assigned to the H-HOPE intervention
      group or an attention control group. H-HOPE is an integrated intervention that
      included (1) twice-daily infant stimulation using the ATVV (auditory, tactile,
      visual, and vestibular-rocking stimulation) and (2) four maternal participatory
      guidance sessions plus two telephone calls by a nurse-community advocate team.
      Mother-infant interaction was assessed at 6-weeks CA using the Nursing Child
      Assessment Satellite Training-Feeding Scale (NCAST, 76 items) and the Dyadic
      Mutuality Code (DMC, 6-item contingency scale during a 5-min play session). NCAST
      and DMC scores for the Control and H-HOPE groups were compared using t-tests, chi
      square tests and multivariable analysis. Compared with the Control group (n =
      76), the H-HOPE group (n = 66) had higher overall NCAST scores and higher
      maternal Social-Emotional Growth Fostering Subscale scores. The H-HOPE group also
      had significantly higher scores for the overall infant subscale and the Infant
      Clarity of Cues Subscale (p < 0.05). H-HOPE dyads were also more likely to have
      high responsiveness during play as measured by the DMC (67.6% versus 58.1% of
      controls). After adjustment for significant maternal and infant characteristics,
      H-HOPE dyads had marginally higher scores during feeding on overall mother-infant
      interaction (beta = 2.03, p = 0.06) and significantly higher scores on the infant
      subscale (beta = 0.75, p = 0.05) when compared to controls. In the adjusted
      analysis, H-HOPE dyads had increased odds of high versus low mutual
      responsiveness during play (OR = 2.37, 95% CI = 0.97, 5.80). Intervening with
      both mother and infant is a promising approach to help premature infants achieve
      the social interaction patterns essential for optimal development.

PMID- 23962545
TI  - Endoscopist specialty: a quality indicator at the population level.

PMID- 23962546
TI  - Severe odynophagia and rapidly progressive dysphagia as an unusual presentation
      of eosinophilic gastroenteritis.

PMID- 23962547
TI  - Gastric metastasis of hepatocellular carcinoma presenting as hematemesis.

PMID- 23962549
TI  - Peroral endoscopic myotomy: technique of mucosal incision.

PMID- 23962548
TI  - Management of dyslipidemia as a cardiovascular risk factor in individuals with
      nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of liver
      disease in the United States and is associated with an increased risk of
      cardiovascular disease (CVD) and cardiovascular (CV) mortality, independent of
      traditional cardiovascular risk factors. CVD is one of the most common causes of
      death among individuals with NAFLD and management of NAFLD must extend beyond
      liver disease to include CVD risk modification. Clinicians should assess CVD risk
      with the Framingham Risk Score and screen for CVD risk factors including
      dyslipidemia, diabetes mellitus, hypertension, tobacco use, and the metabolic
      syndrome. CVD risk factors, particularly dyslipidemia, require aggressive medical
      management to reduce the high risk of CVD events and death in individuals with
      NAFLD.

PMID- 23962550
TI  - Finding the needle in the haystack: predicting mortality in pregnancy-related
      liver disease.

PMID- 23962551
TI  - Radiologic and histologic heterogeneity in a case of autoimmune acute liver
      failure.

PMID- 23962552
TI  - Factors associated with risk for colorectal cancer recurrence after endoscopic
      resection of T1 tumors.
AB  - BACKGROUND & AIMS: More information is needed on the long-term outcomes of
      patients who undergo endoscopic resection of colorectal tumors. We evaluated
      recurrence of colorectal cancer (CRC) after endoscopic resection or a combination
      of endoscopic research and surgery for T1 colorectal tumors. METHODS: We
      conducted a retrospective study of 389 patients with T1 CRC treated by endoscopic
      resection from January 1989 to December 2008 in Sapporo, Japan. We compared
      outcomes between patients who underwent subsequent surgery (ER + SURG, n = 205)
      and those who did not (ER only, n = 184) and statistically adjusted baseline
      differences between the groups according to the propensity scores. RESULTS: There
      was almost no risk of cancer recurrence among patients without indications for
      surgery recommended by the Japanese Society for Cancer of the Colon and Rectum
      (these indications include tumors with vertical margins, deep submucosal
      invasion, lymphatic or venous invasion, poor differentiation, or high-grade
      budding). Among patients with indications for surgery, the cumulative risks of
      recurrence (CRRs) were 3.7% in the ER + SURG group and 20.1% in the ER only group
      (P = .001). However, the patients with only deep submucosal invasion had a low
      CRR, even without surgery (2.3% in the ER + SURG group and 3.4% in the ER only
      groups, P = .867). In contrast, patients with indications for surgery other than
      deep submucosal invasion (high-risk patients) had much better outcomes when they
      also underwent surgery (CRRs: 5.8% in the ER + SURG group vs 58.0% in the ER only
      group, P < .001). CONCLUSIONS: On the basis of a retrospective study of patients
      who underwent endoscopic resection for T1 CRC, those with tumors with only
      submucosal invasion are at low risk for cancer recurrence. However, patients with
      other high-risk tumor features have greater risks for cancer recurrence and
      benefit from subsequent surgery.

PMID- 23962554
TI  - An unusual cause of occlusion of a fully covered self-expandable metallic stent
      by biliary ascarides.

PMID- 23962553
TI  - Familial colorectal cancer, beyond Lynch syndrome.
AB  - Although 30% of individuals diagnosed with colorectal cancer (CRC) report a
      family history of the disease, only 5% to 6% carry germline mutations in genes
      associated with known hereditary cancer syndromes. The evaluation and management
      of families affected with CRC can be complicated by variability in disease
      phenotypes and limited sensitivity of genetic tests. In this review, we examine
      what is currently known about familial CRC and what we have yet to learn, and
      explore how novel genomic approaches might be used to identify additional genetic
      and epigenetic factors implicated in heritable risk for cancer.

PMID- 23962555
TI  - Gender-specific transcriptional profiling of marine medaka (Oryzias melastigma)
      liver upon BDE-47 exposure.
AB  - Marine medaka (Oryzias melastigma) were exposed to 2,2',4,4'-tetrabromodiphenyl
      ether (BDE-47) to investigate the gender-specific transcriptional profiles of
      liver tissue in response to this flame retardant. A cDNA library of O. melastigma
      was constructed, and 2304 clones were amplified from the library to fabricate a
      cDNA microarray. Sequences of these genes were assembled into 1800 sequences
      using Geneious, a bioinformatics software. Corresponding expressed sequence tags
      were blasted against the National Centre for Biotechnology Information non
      redundant database and further classified into various biological categories
      according to the Gene Ontology project. Male and female three-month-old were fed
      a diet of BDE-47 contaminated Artemia at low dosage (290.3+/-172.3ng BDE-47/day)
      and high dosage (580.5+/-344.6ng BDE-47/day) for 5 and 21 days, respectively. The
      transcriptional profiles of O. melastigma liver were then generated by the
      species-specific cDNA microrarray. The results from microarray analysis suggested
      very different gene expression patterns between males and females for both BDE-47
      exposure-dose and exposure-time, with male livers having stronger gene regulatory
      responses than female livers. Importantly, our results revealed that in male O.
      melastigma only, BDE-47 exposure may activate phosphoinositide-3-kinase and
      mitogen-activated protein kinase, proteins that play importance roles in cell
      growth, proliferation and survival.

PMID- 23962556
TI  - MiR-101 inhibits melanoma cell invasion and proliferation by targeting MITF and
      EZH2.
AB  - The microRNA miR-101 has been reported to be a tumor suppressor. Here we show
      that low expression of miR-101 is associated with poor survival in stage IV
      melanoma patients. We identified microphthalmia-associated transcription factor
      (MITF) as a direct target of miR-101. In melanoma cells, overexpression of miR
      101 downregulated protein levels of MITF and a previously reported target
      protein, enhancer of zeste homolog 2 (EZH2). Functional assays showed that miR
      101 suppressed invasion and proliferation - an outcome that could be phenocopied
      by siRNA knockdown of MITF and EZH2. Our data suggest that miR-101 might have a
      beneficial role in melanoma. 

PMID- 23962557
TI  - Targeting GD2 ganglioside and aurora A kinase as a dual strategy leading to cell
      death in cultures of human neuroblastoma cells.
AB  - The mechanism of the inhibitory effect of anti-GD2 ganglioside (GD2) 14G2a mouse
      monoclonal antibody (mAb) on human neuroblastoma cells survival was studied in
      vitro. It was recently shown in IMR-32 cells that death induced by this antibody
      exhibited several characteristics typical of apoptosis. In this study we used
      cytotoxixity assays, qRT-PCR and immunoblotting to evaluate the response of
      several human neuroblastoma cell lines to the anti-GD2 14G2a mAb. We showed that
      the mAb decreases all three aurora kinases expression and phosphorylation in IMR
      32 and LA-N-1 cells. Most importantly, we show, that MK-5108 specific aurora A
      kinase inhibitor decreases neuroblastoma cell survival, and when used in
      combination with the mAb, significantly potentiates cytotoxicity against IMR-32,
      CHP-134, and LA-N-5 neuroblastoma cells in vitro. It was shown that
      downregulation of aurora A kinase by the therapeutic antibody is associated with
      decreased levels of MYCN protein in cytoplasm, and induced expression of PHLDA1
      and P53 proteins. 

PMID- 23962558
TI  - Abrogation of constitutive Stat3 activity circumvents cisplatin resistant ovarian
      cancer.
AB  - The aim of the present study was to investigate the role of Stat3 in cisplatin
      resistant ovarian cancer. It was first demonstrated that higher activated Stat3
      was detected in cisplatin-resistant ovarian cancer cell lines. To provide
      evidence that supported the hypothesis that phosphorylated-Stat3 expression may
      promote cisplatin resistance, ectopic Stat3 was expressed by IL-6 stimulation
      that partially abrogates Stat3, as opposed to the knock-down of Stat3 by specific
      siRNA that restores cisplatin sensitivity against ovarian cancer cells. This
      hypothesis was further confirmed by clinical tumor specimens of ovarian cancer
      obtained from patients with cisplatin-resistance. Based on these premises,
      Stattic, an effective small molecular inhibitor of Stat3, was used to inhibit
      Stat3 activation. The data presented here show that Stattic restored the
      sensitivity to cisplatin in chemoresistant ovarian cancer by significant
      reductions in the expression of the anti-apoptosis protein Bcl-2, Bcl-XL,
      Survivin protein and phosphorylated-Akt levels. Consistent with these
      observations, this experiment demonstrated the first evidence of Stattic
      circumvented cisplatin resistance of orthotopic xenograft ovarian cancer in vivo.
      Altogether, these findings emphasize the importance of Stat3 in cisplatin
      resistance in ovarian cancer and provide a further impetus to clinically evaluate
      biological modifiers that may circumvent cisplatin resistance in patients with
      chemoresistant ovarian cancer.

PMID- 23962559
TI  - Targeted abrogation of diverse signal transduction cascades by emodin for the
      treatment of inflammatory disorders and cancer.
AB  - Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a natural occurring
      anthraquinone derivative isolated from roots and barks of numerous plants, molds,
      and lichens. It is found as an active ingredient in different Chinese herbs
      including Rheum palmatum and Polygonam multiflorum, and has diuretic,
      vasorelaxant, anti-bacterial, anti-viral, anti-ulcerogenic, anti-inflammatory,
      and anti-cancer effects. The anti-inflammatory effects of emodin have been
      exhibited in various in vitro as well as in vivo models of inflammation including
      pancreatitis, arthritis, asthma, atherosclerosis and glomerulonephritis. As an
      anti-cancer agent, emodin has been shown to suppress the growth of various tumor
      cell lines including hepatocellular carcinoma, pancreatic, breast, colorectal,
      leukemia, and lung cancers. Emodin is a pleiotropic molecule capable of
      interacting with several major molecular targets including NF-kappaB, casein
      kinase II, HER2/neu, HIF-1alpha, AKT/mTOR, STAT3, CXCR4, topoisomerase II, p53,
      p21, and androgen receptors which are involved in inflammation and cancer. This
      review summarizes reported anti-inflammatory and anti-cancer effects of emodin,
      and re-emphasizes its potential therapeutic role in the treatment of inflammatory
      diseases and cancer. 

PMID- 23962560
TI  - Glypican-5 is a novel metastasis suppressor gene in non-small cell lung cancer.
AB  - Glypican-5 (GPC5) may be a potential tumor suppressor gene in non-small cell lung
      cancer (NSCLC). The present study aimed to clarify the GPC5 expression pattern
      and to explore its potential functions in NSCLC. The expression of GPC5 gene was
      lower in lung cancer tissues compared with adjacent noncancerous tissues. The
      GPC5 gene expression in the lymph node metastasis group was remarkably lower than
      that in the non-metastasis group. The tissue microarray (TMA) study found that
      the overall survival rate of GPC5-positive group was significantly higher than
      that of GPC5-negative group in AC subgroup. Overexpressing GPC5 in NSCLC cell
      lines significantly suppressed their migration, invasion, and proliferation
      activities and also induced G1/S phase arrest of the cells in vitro. Our data
      suggest that GPC5 is a novel metastasis suppressor gene in NSCLC and may be a
      potential biomarker that predicts NSCLC metastasis. 

PMID- 23962561
TI  - Application of the concept synthetic lethality toward anticancer therapy: a
      promise fulfilled?
AB  - Back in 1997, a suggestion to apply the concept of synthetic lethality towards
      the development of selective, less toxic, cancer drugs and anticancer targets,
      was brought forward. The availability of large scale synthetic, low-molecular
      weight chemical libraries seemed to lend itself to the concept. Human/mouse
      genome-wide siRNAs and shRNA-expressing libraries allowing high throughput
      screening for target genes synergistic lethal with defined human cancer
      aberrations, also raised high hopes of a soon to be established selective
      therapy. Sixteen years later, the major experimental aspects relating to the
      implementation of this more focused approach to cancer drug discovery, is briefly
      and critically reviewed. 

PMID- 23962562
TI  - Characterization of sildenafil citrate tablets of different sources by near
      infrared chemical imaging and chemometric tools.
AB  - The chemical imaging technique by near infrared spectroscopy was applied for
      characterization of formulations in tablets of sildenafil citrate of six
      different sources. Five formulations were provided by Brazilian Federal Police
      and correspond to several trademarks of prohibited marketing and one was an
      authentic sample of Viagra. In a first step of the study, multivariate curve
      resolution was properly chosen for the estimation of the distribution map of
      concentration of the active ingredient in tablets of different sources, where the
      chemical composition of all excipients constituents was not truly known. In such
      cases, it is very difficult to establish an appropriate calibration technique, so
      that only the information of sildenafil is considered independently of the
      excipients. This determination was possible only by reaching the second-order
      advantage, where the analyte quantification can be performed in the presence of
      unknown interferences. In a second step, the normalized histograms of images from
      active ingredient were grouped according to their similarities by hierarchical
      cluster analysis. Finally it was possible to recognize the patterns of
      distribution maps of concentration of sildenafil citrate, distinguishing the true
      formulation of Viagra. This concept can be used to improve the knowledge of
      industrial products and processes, as well as, for characterization of
      counterfeit drugs. 

PMID- 23962563
TI  - Effect of rapid modulation of circulating plasma testosterone concentration on
      begging, aggressive behavior and competition for food in black-headed gull (Larus
      ridibundus) chicks.
AB  - Sibling competition mediated by begging behavior is extremely common in avian
      species and recent studies have highlighted the role of endogenous testosterone
      in regulating such phenomenon. However, current literature depicts an
      inconsistent pattern in altricial vs. semi-precocial species, with stimulating
      versus inhibitory effects of the hormone respectively. This is possibly due to a
      difference in the methodology of hormone treatment (short-term moderate dose
      versus a long-term stronger elevation, respectively) between the studies
      performed so far. In this study, we induced short-term moderate peaks in plasma
      testosterone levels, as applied in altricial bird species, and assessed the
      effects of our manipulation on begging, competitive and aggressive behavior in
      black-headed gull (Larus ridibundus) chicks, a semi-precocial species. Our
      results suggest that, unlike in altricial songbirds, temporary increase of plasma
      testosterone concentration suppresses begging and enhances aggressiveness towards
      intruders. However, it also increases aggression and the chances of getting
      priority while scrambling with nest mates to gain access to food. Thus, the
      inconsistencies in the hormonal control of begging behavior observed between
      altricial vs. semi-precocial birds seem real and perhaps related to species
      differences in complexity of the display and the nature of competition. These may
      be elucidated by future comparative studies. 

PMID- 23962564
TI  - C-peptide inhibitors of Ebola virus glycoprotein-mediated cell entry: effects of
      conjugation to cholesterol and side chain-side chain crosslinking.
AB  - We previously described potent inhibition of Ebola virus entry by a 'C-peptide'
      based on the GP2 C-heptad repeat region (CHR) targeted to endosomes ('Tat-Ebo').
      Here, we report the synthesis and evaluation of C-peptides conjugated to
      cholesterol, and Tat-Ebo analogs containing covalent side chain-side chain
      crosslinks to promote alpha-helical conformation. We found that the cholesterol
      conjugated C-peptides were potent inhibitors of Ebola virus glycoprotein (GP)
      mediated cell entry (~10(3)-fold reduction in infection at 40 MUM). However, this
      mechanism of inhibition is somewhat non-specific because the cholesterol
      conjugated peptides also inhibited cell entry mediated by vesicular stomatitis
      virus glycoprotein G. One side chain-side chain crosslinked peptide had
      moderately higher activity than the parent compound Tat-Ebo. Circular dichroism
      revealed that the cholesterol-conjugated peptides unexpectedly formed a strong
      alpha-helical conformation that was independent of concentration. Side chain-side
      chain crosslinking enhanced alpha-helical stability of the Tat-Ebo variants, but
      only at neutral pH. These result provide insight into mechanisms of C-peptide
      inhibiton of Ebola virus GP-mediated cell entry.

PMID- 23962565
TI  - Preparation of inulin-type fructooligosaccharides using fast protein liquid
      chromatography coupled with refractive index detection.
AB  - A fast protein liquid chromatography coupled with refractive index detection
      (FPLC-RID) method was firstly developed for preparation and purification of
      fructooligosaccharides with different degree of polymerization from burdock,
      Arctium lappa. After extraction with 60% ethanol and decolorization with MCI gel
      CHP20P, total fructooligosaccharides were purified on Bio-Gel P-2 column eluted
      with water at the flow rate of 0.3 ml/min, which was the optimized conditions.
      The obtained fructooligosaccharides with degree of polymerization of 3-9 were
      identified based on their methylation analysis, MS and NMR data. This method has
      the advantages of high automation, good recovery and easy performance, which
      could be used for preparation of FOS from other sources, as well as other
      targeted compounds without UV absorbance.

PMID- 23962566
TI  - Cumulative area of peaks in a multidimensional high performance liquid
      chromatogram.
AB  - An algorithm was developed to recognize peaks in a multidimensional separation
      and calculate their cumulative peak area. To find the retention times of peaks in
      a one dimensional chromatogram, the Savitzky-Golay smoothing filter was used to
      smooth and find the first through third derivatives of the experimental profiles.
      Close examination of the shape of these curves informs on the number of peaks
      that are present and provides starting values for fitting theoretical profiles.
      Due to the nature of comprehensive multidimensional HPLC, adjacent cut fractions
      may contain compounds common to more than one cut fraction. The algorithm
      determines which components were common in adjacent cuts and subsequently
      calculates the area of a two-dimensional peak profile by interpolating the
      surface of the 2D peaks between adjacent peaks. This algorithm was tested by
      calculating the cumulative peak area of a series of 2D-HPLC separations of
      alkylbenzenes, phenol and caffeine with varied concentrations. A good
      relationship was found between the concentration and the cumulative peak area.

PMID- 23962567
TI  - HDAC expression patterns in pediatric ALL.

PMID- 23962568
TI  - DNMT3A mutation is a poor prognosis biomarker in AML: results of a meta-analysis
      of 4500 AML patients.
AB  - Somatic DNA methyl transferase 3A (DNMT3A) mutations have been recognized
      recently as recurrent molecular aberrations in acute myeloid leukemia (AML). The
      precise role of these mutations in leukemogenesis remains elusive but a number of
      studies have already been conducted to study their potential prognostic value in
      AML patients with variable results. We performed a meta-analysis on published
      data from over 4500 AML patients to provide robust evidence supporting DNMT3A
      mutation testing in clinical setting for AML patients. Our meta-analysis showed
      that DNMT3A mutations were associated with M4 and M5 AML subtypes. Those
      mutations conferred significantly worse prognosis with both shorter OS (p=0.0004)
      and shorter RFS (p=0.002). Notably, DNMT3A mutations appeared to be an
      independent adverse prognostic factor also in younger patients with normal
      cytogenetics AML (OS (p=0.01) and RFS (p=0.0005)) and also in the subgroup of
      patients with high risk genotypes defined according to the criteria of the
      European Leukemia Net (ELN) (OS (p=0.002)). Therefore, DNMT3A mutational status
      can improve the risk stratification of AML patients in the setting of integrated
      mutational profiling. 

PMID- 23962569
TI  - Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its
      attenuation by Ibrutinib induces apoptosis.
AB  - Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy that
      characteristically shows overexpression of cyclin-D1 due to an alteration in the
      t(11;14)(q13;q32) chromosomal region. Although there are some promising treatment
      modalities, great majority of patients with this disease remain incurable. The B
      cell antigen receptor (BCR) signaling plays a crucial role in B-cell biology and
      lymphomagenesis. Bruton tyrosine kinase (BTK) has been identified as a key
      component of the BCR signaling pathway. Evidence suggests that the blockade of
      BTK activity by potent pharmacologic inhibitors attenuates BCR signaling and
      induces cell death. Notably, the expression levels and the role of BTK in MCL
      survival are still elusive. Here, we demonstrated a moderate to strong BTK
      expression in all MCL cases (n=19) compared to benign lymphoid tissues. Treatment
      of MCL cell lines (Mino or Jeko-1) with a potent BTK pharmacologic inhibitor,
      Ibrutinib, decreased phospho-BTK-Tyr(223) expression. Consistent with this
      observation, Ibrutinib inhibited the viability of both Mino and JeKo-1 cells in
      concentration- and time-dependent manners. Ibrutinib also induced a concentration
      dependent apoptosis in both cell lines. Consistently, Ibrutinib treatment
      decreased the levels of anti-apoptotic Bcl-2, Bcl-xL, and Mcl-1 protein. These
      findings suggest that BTK signaling plays a critical role in MCL cell survival,
      and the targeting of BTK could represent a promising therapeutic modality for
      aggressive lymphoma. 

PMID- 23962571
TI  - Late-occurring giant adrenal myelolipoma in a patient with congenital adrenal
      hyperplasia.

PMID- 23962570
TI  - Central myelin gene expression during postnatal development in rats exposed to
      nicotine gestationally.
AB  - Abnormal myelin gene expression in the central nervous system (CNS) is associated
      with many mental illnesses, including psychiatric disorders and drug addiction.
      We have previously shown that prenatal exposure to nicotine, the major
      psychoactive component in cigarette smoke, alters myelin gene expression in the
      CNS of adolescent rats. To examine whether this effect is specific for
      adolescents, we examined myelin gene expression in the CNS of juveniles and
      adults. Pregnant Sprague-Dawley rats were treated with nicotine (3 mg/kg/day; GN)
      or saline (GS) via osmotic mini pumps from gestational days 4-18. Both male and
      female offspring were sacrificed at postnatal day P20-21 (juveniles), P35-36
      (adolescents), or P59-60 (adults). Three limbic brain regions, the prefrontal
      cortex (PFC), caudate putamen (CPu), and nucleus accumbens (NAc), were dissected.
      The expression of genes encoding major myelin components was evaluated using
      quantitative RT-PCR. We found that GN altered myelin gene expression in juveniles
      with brain region and sex differences. The pattern of alteration was different
      from that observed in adolescents. Although these genes were expressed normally
      in male adults, we observed decreased expression in GN-treated female adults,
      especially in the CPu. Thus, GN altered myelin gene expression throughout
      postnatal development and adulthood. The effect on adolescents was quite
      different from that at other ages, which correlated with the unique symptoms of
      many psychiatric disorders during adolescence.

PMID- 23962572
TI  - Use of music to reduce anxiety during office hysteroscopy: prospective randomized
      trial.
AB  - STUDY OBJECTIVE: To investigate the effects of music on anxiety and perception of
      pain during office hysteroscopy. DESIGN: Prospective randomized trial (Canadian
      Task Force classification I). SETTING: Major university medical center.
      INTERVENTIONS: Three hundred fifty-six patients were enrolled between July 2012
      and January 2013. Hysteroscopy was performed in a dedicated ambulatory room,
      using vaginoscopy and without any type of anesthesia. A Bettocchi hysteroscope 5
      mm in diameter was used. All procedures were performed by the same surgeon, a
      gynecologist with special interest in hysteroscopy. MEASUREMENTS AND MAIN
      RESULTS: Data collected included age, body mass index, number of vaginal
      deliveries, educational achievement level, and history of endometrial surgery
      (curettage and/or hysteroscopy). For each patient, vital parameters such as blood
      pressure, heart rate, and respiratory rate were recorded 15 minutes before the
      procedure and during hysteroscopy after traversing the cervix. Wait time before
      surgery and the duration of the procedure were also recorded. A completed Italian
      version of the state anxiety questionnaire (State-Trait Anxiety Inventory) and a
      visual analog scale (VAS) were administered to each patient before and after the
      procedure. The t test and Mann-Whitney U test was used when appropriate to
      compare the 2 groups. Statistical significance was accepted at p = .05. During
      surgery, systolic blood pressure and heart rate were significantly lower in the
      music group compared with the no music group. Women in the music group
      experienced significantly lower anxiety after hysteroscopy and less pain during
      the procedure, and a significant decrease in both anxiety and pain scores after
      hysteroscopy. Postoperative State-Trait Anxiety Inventory form Y1 and VAS scores
      were significantly lower in the music group. CONCLUSION: Music can be useful as a
      complementary method to control anxiety and reduce perception of pain. The
      patient is more relaxed and experiences less discomfort.

PMID- 23962573
TI  - Risk of incidental finding of endometrial cancer at the time of hysterectomy for
      benign condition.
AB  - STUDY OBJECTIVE: To assess the risk of unanticipated endometrial carcinoma during
      hysterectomy to treat a presumed benign condition. DESIGN: Retrospective analysis
      (Canadian Task Force classification II-2). SETTING: Tertiary referral center,
      university hospital. PATIENTS: All women who underwent hysterectomy to treat
      presumed benign indications at our center from January 2000 to December 2011 were
      identified. We analyzed all pathologic reports and identified cases of unexpected
      endometrial carcinoma. INTERVENTIONS: Hysterectomy by any approach to treat
      presumed benign indications. MEASUREMENTS AND MAIN RESULTS: At our institution,
      2179 hysterectomies were performed to treat presumed benign indications. Nine
      (0.4%) revealed unexpected endometrial carcinoma (95% confidence interval, 0.2
      0.7). CONCLUSION: Our data suggest that the rate of unanticipated endometrial
      carcinoma during hysterectomy to treat benign conditions is low.

PMID- 23962574
TI  - Cellular, histologic, and molecular changes associated with endometriosis and
      ovarian cancer.
AB  - Our understanding of the pathogenesis of endometriosis is rapidly evolving as
      early molecular events are increasingly identified. Endometriosis is associated
      with increased risk of ovarian cancer and exhibits neoplastic phenotypes
      including invasion of stromal tissue and lymphatic spread to distant organs. This
      review of the literature establishes the clinical, epidemiologic, and pathologic
      correlation between endometriosis and low-grade ovarian cancer. Genetic studies
      have demonstrated that endometriotic lesions have mutations in genes directly
      related to neoplasms, in particular the p53, KRAS, PTEN, and ARID1A genes, which
      suggests a direct transition from a subset of endometriotic lesions to invasive
      carcinomas. The identification of both genetic and epigenetic biomarkers
      including microRNAs are essential for identifying patients at risk for the
      transition to neoplasia.

PMID- 23962575
TI  - Universal health coverage and user charges.
AB  - There has been an explosion of interest in the concept of 'universal health
      coverage', fuelled by publication of the World Health Report 2010. This paper
      argues that the system of user charges for health services is a fundamental
      determinant of levels of coverage. A charge can lead to a loss of utility in two
      ways. Citizens who are deterred from using services by the charge will suffer an
      adverse health impact. And citizens who use the service will suffer a loss of
      wealth. The role of social health insurance is threefold: to reduce households'
      financial risk associated with sickness; to promote enhanced access to needed
      health services; and to contribute to societal equity objectives, through an
      implicit financial transfer from rich to poor and healthy to sick. In principle,
      an optimal user charge policy can ensure that the social health insurance funds
      are used to best effect in pursuit of these objectives. This paper calls for a
      fundamental rethink of attitudes and policy towards user charges.

PMID- 23962576
TI  - Determinants of health in discharge planning for seniors: asking the right
      questions.
AB  - Practitioners are encouraged to consider a shift in their philosophy regarding
      the manner in which interdisciplinary health care teams ask questions of seniors
      and their caregivers in the hospital discharge process. By engaging with a
      discharge framework that encompasses a social-determinants-of-health lens,
      discharge planning teams can begin to systematically ask questions that move
      beyond the traditional medical focus on prescriptions, rehabilitation, and
      treatments. This approach may reveal strengths and also expose health and social
      inequities that seniors might face upon their arrival home. This information may
      open a gateway for connecting seniors to social and economic resources that will
      support them in remaining productive and healthy.

PMID- 23962577
TI  - Is malarial anaemia homologous to neocytolysis after altitude acclimatisation?
AB  - Malaria patients frequently develop severe anaemia that can persist after
      Plasmodium infection has been cleared from the circulation. This puzzling
      phenomenon involves massive death of young uninfected erythrocytes at a time when
      parasitic infection is very low. We have observed striking similarities in
      erythrocyte homoeostasis during altitude acclimatisation and Plasmodium
      infection, both of which initially induce an increase in circulating
      erythropoietin (Epo). Decreasing levels of Epo after return to low altitudes
      induce the death of young erythrocytes, a phenomenon called neocytolysis. In a
      similar way, we propose that Epo, which peaks during acute malaria and decreases
      after parasite clearance, could be contributing to anaemia causing neocytolysis
      during recovery from Plasmodium infection. 

PMID- 23962578
TI  - A survey of the attitudes and perceptions of multidisciplinary team members
      towards family presence at bedside rounds in the intensive care unit.
AB  - OBJECTIVE: To describe the attitudes and perceptions of intensive care unit (ICU)
      staff [critical care physicians and fellows (MDs), registered nurses (RNs),
      allied health discipline (HD) and managers] towards family presence at bedside
      rounds. RESEARCH METHODOLOGY: We developed, tested and administered a
      questionnaire to the multidisciplinary staff. SETTING: 24-Bed medical surgical
      ICU. RESULTS: 160/221 (72.4%) individuals responded, including 12 MDs, 95 RNs, 48
      HD personnel, 4 managers and 1 unspecified. While most MDs strongly agreed and HD
      and management groups somewhat agreed, most RNs strongly disagreed with providing
      family members the option to attend rounds. Over 50% of respondents either
      strongly or somewhat agreed that the presence of family members prolongs rounds,
      reduces the medical education provided to the team and constrains delivery of
      negative medical information. Compared to MDs, RNs expressed greater reservation
      to family presence at rounds. Among RNs, more experienced RNs, expressed greater
      reservation with family presence during rounds. CONCLUSION: We found significant
      differences among the attitudes of health care providers towards family presence
      at bedside rounds with RNs, especially more experienced RNs, expressing the
      greatest reservation. Qualitative research is required to explore perceived and
      actual barriers to family member presence at rounds.

PMID- 23962579
TI  - A description of the ICU liaison nurse role in Argentina.
AB  - BACKGROUND: Recognising and responding to clinical deterioration in hospital
      patients has been promoted by many western countries to improve patient safety.
      In non-western and developing countries it is likely to be even more important to
      focus on strategies of patient safety. This paper reflects the services provided
      by Intensive Care Unit Liaison Nurses (ICULN) in the first year of their work,
      July 2010-June 2011, in an Argentinean hospital. OBJECTIVES: This practice audit
      aimed to describe the ICULN patient care activities performed for patients
      discharged from the ICU and ward patients with complex care needs, and to
      identify education activities carried with ward nursing staff caring for these
      patients. METHODS: Experienced critical care nurses, with strong communication
      and education skills were appointed as ICULNs. They were asked to assess ward
      patients transferred from ICU once per shift and ward patients as requested by
      staff. They had to provide patient complex care if necessary and education to
      ward nurses caring for these patients. RESULTS: A total of 387 patients were
      followed by ICULNs. The median age of patients was 49 (IQR 26) years (range 15
      89). A total of 369 (95.3%) of the patients were discharged from ICU and 18
      (4.7%) were ward patients who required complex care. The most frequent conditions
      patients had were surgery, neurologic conditions, trauma and sepsis. Thirty four
      (9.2%) of 369 patients who were initially in ICU, were readmitted during the same
      hospitalisation. During the study period ICULNs performed 5973 patient care and
      1709 staff education activities. CONCLUSION: ICULNs provide advanced assessment
      and surveillance of ICU discharged and complex ward patients, and facilitate ICU
      ward transition assisting and educating ward staff. Further evaluation is
      necessary to better describe the role in Argentina and the effect of ICULN
      service on patient outcomes and on staff.

PMID- 23962580
TI  - Enhanced photocatalytic hydrogen generation over ZrO2-TiO2-CdS hybrid structure.
AB  - Hybrid photocatalysts with suitable band structures are expected to show enhanced
      photocatalytic activity as compared to their constituent single phase compounds
      due to their improved physico-chemical properties. Here, we report an enhanced
      photocatalytic activity of a new composite photocatalyst comprising of ZrO2,
      TiO2, and CdS. This hybrid catalyst exhibits increased photocatalytic activity
      for hydrogen generation from water as compared to their constituent compounds.
      The photocatalytic activity decreases in the order: ZrO2-TiO2-CdS>TiO2-CdS>ZrO2
      CdS>CdS>ZrO2-TiO2~TiO2>ZrO2. An apparent quantum efficiency of 11.5% is obtained
      for ZrO2-TiO2-CdS with Pd as co-catalyst. Absorption edge of the composite is
      slightly blue shifted compared with that of pure CdS. Photoluminescence lifetime
      studies indicate an increased lifetime for the charge carriers in the composite
      sample as compared to that of pure CdS. Transmission electron microscopy images
      reveal that the particle size of the composite is much less than that of single
      phase CdS. The enhanced photocatalytic activity of the composite is attributed to
      the decreased particle size of CdS and increased lifetime of the charge carriers
      resulting from the efficient interfacial transfer of photogenerated electrons at
      the CdS/TiO2 and CdS/ZrO2 interface. 

PMID- 23962582
TI  - Adult dermatomyositis associated with lipodystrophy.

PMID- 23962581
TI  - Association between TLR3 rs3775291 and resistance to HIV among highly exposed
      Caucasian intravenous drug users.
AB  - BACKGROUND: TLR3 recognizes dsRNA and triggers immune responses against RNA and
      DNA viruses. A polymorphism in TLR3, rs3775291 (Leu412Phe), has been associated
      with the increased susceptibility to enteroviral myocarditis, protection against
      tick-borne encephalitis virus and HIV-1 infection. We investigated Caucasian
      intravenous drug users (IDUs) and blood donors in order to evaluate the
      associations between TLR3 genotypes and susceptibility to HIV infection.
      MATERIALS AND METHODS: A total of 345 Caucasian IDUs were recruited, 50% of them
      were HIV positive, 89% HCV and 77% HBV positive. Based on their history of needle
      sharing, 20 of the HIV negative IDUs were classified as highly exposed HIV
      seronegatives (HESNs), 68 as non-HESNs and 85 as unexposed. The control group
      consisting of 497 blood donors tested negative for all three viruses. TLR3
      rs3775291 were determined by using TaqMan Allelic Discrimination Assay. RESULTS:
      The TLR3 rs3775291 T allele frequency was similar among the HIV negative and HIV
      positive IDUs and blood donors - 36%, 31% and 34%, respectively. The frequency of
      persons possessing at least one TLR3 rs3775291 T allele was significantly higher
      in HESNs compared with blood donors and HIV positive IDUs (80% vs. 55%; p=0.037
      and 80% vs. 53%; p=0.031, respectively). In the univariate analysis, persons who
      possessed at least one T allele had reduced odds of being HIV seropositive
      (OR=0.29, 95% CI=0.09-0.90). This association remained significant (OR=0.25, 95%
      CI=0.07-0.87) after the adjustment for other co-variates (HCV, HBV serostatus and
      duration of intravenous drug use). CONCLUSIONS: The TLR3 rs3775291 T allele has a
      protective effect against HIV infection among HESNs IDUs.

PMID- 23962583
TI  - Photodistributed erythema multiforme.
AB  - Although the existence of photodistributed erythema multiforme has been
      recognized for years, few cases have been described to date. It is an uncommon,
      and probably underdiagnosed, skin disorder that can affect individuals of both
      sexes and all ages. It has been associated with drugs, reactivation of herpes
      simplex virus infection, and polymorphous light eruption. A diagnosis is made on
      the basis of history, physical examination, histology, and phototesting. The
      condition runs a benign, self-limiting course but patients may experience
      outbreaks for several years if the causative agent is not eliminated. It is
      treated symptomatically and patients are advised to avoid triggers and excessive
      sun exposure. 

PMID- 23962584
TI  - Response to comments on "Late-onset acquired generalized lipodystrophy with
      muscle involvement".

PMID- 23962585
TI  - The assessment of the readiness of five countries to implement child maltreatment
      prevention programs on a large scale.
AB  - This study aimed to systematically assess the readiness of five countries -
      Brazil, the Former Yugoslav Republic of Macedonia, Malaysia, Saudi Arabia, and
      South Africa - to implement evidence-based child maltreatment prevention programs
      on a large scale. To this end, it applied a recently developed method called
      Readiness Assessment for the Prevention of Child Maltreatment based on two
      parallel 100-item instruments. The first measures the knowledge, attitudes, and
      beliefs concerning child maltreatment prevention of key informants; the second,
      completed by child maltreatment prevention experts using all available data in
      the country, produces a more objective assessment readiness. The instruments
      cover all of the main aspects of readiness including, for instance, availability
      of scientific data on the problem, legislation and policies, will to address the
      problem, and material resources. Key informant scores ranged from 31.2 (Brazil)
      to 45.8/100 (the Former Yugoslav Republic of Macedonia) and expert scores, from
      35.2 (Brazil) to 56/100 (Malaysia). Major gaps identified in almost all countries
      included a lack of professionals with the skills, knowledge, and expertise to
      implement evidence-based child maltreatment programs and of institutions to train
      them; inadequate funding, infrastructure, and equipment; extreme rarity of
      outcome evaluations of prevention programs; and lack of national prevalence
      surveys of child maltreatment. In sum, the five countries are in a low to
      moderate state of readiness to implement evidence-based child maltreatment
      prevention programs on a large scale. Such an assessment of readiness - the first
      of its kind - allows gaps to be identified and then addressed to increase the
      likelihood of program success. 

PMID- 23962586
TI  - Development of a Luminex assay for the detection of swine antibodies to non
      structural proteins of foot-and-mouth disease virus.
AB  - Foot-and mouth disease (FMD), swine vesicular disease (SVD), and vesicular
      stomatitis (VS) are highly contagious vesicular diseases of swine but are not
      easy to differentiate clinically. For the purpose of instant detecting of FMD and
      differentiating it from the other vesicular diseases, a Luminex assay was
      developed. Sera from 64 infected, 307 vaccinated, and 280 naive pigs were tested
      by the Luminex assay. Diagnostic sensitivity of the assay was 100%. Diagnostic
      specificity of the assay was 98.7% in vaccinated pigs and 97.5% to 100% in naive
      pigs. Agreement between the results from the Luminex assay and those from a 3ABC
      polypeptide blocking ELISA was 96.3% with kappa statistics of 0.92. The Luminex
      assay can detect the immune response to NSP-3ABC in swine as early as eight days
      post-infection. Moreover, all of the 15 vaccinated but unprotected pigs were all
      detected by the Luminex assay. The results indicated that the Luminex assay has
      potential with specificity in detecting antibodies to FMDV 3ABC NSP and in
      distinguishing FMDV-infected pigs from with either SVDV or VSV. 

PMID- 23962587
TI  - Clinical trials provide the evidence critical for patient empowerment.

PMID- 23962588
TI  - Universal health coverage and user charges: response to commentaries.

PMID- 23962589
TI  - Is the sham acupuncture group a real sham control group? Comments on "Vas J et
      al. Acupuncture in patients with acute low back pain: a multicentre randomised
      controlled clinical trial [PAIN(r) 2012;153(9):1883-9]".

PMID- 23962590
TI  - Discrepancies between registered and published primary outcome specifications in
      analgesic trials: ACTTION systematic review and recommendations.
AB  - The National Institutes of Health released the trial registry ClinicalTrials.gov
      in 2000 to increase public reporting and clinical trial transparency. This
      systematic review examined whether registered primary outcome specifications
      (POS; ie, definitions, timing, and analytic plans) in analgesic treatment trials
      correspond with published POS. Trials with accompanying publications (n = 87)
      were selected from the Repository of Registered Analgesic Clinical Trials
      (RReACT) database of all postherpetic neuralgia, diabetic peripheral neuropathy,
      and fibromyalgia clinical trials registered at ClinicalTrials.gov as of December
      1, 2011. POS never matched precisely; discrepancies occurred in 79% of the
      registry-publication pairs (21% failed to register or publish primary outcomes
      [PO]). These percentages did not differ significantly between industry and non
      industry-sponsored trials. Thirty percent of the trials contained unambiguous POS
      discrepancies (eg, omitting a registered PO from the publication, "demoting" a
      registered PO to a published secondary outcome), with a statistically
      significantly higher percentage of non-industry-sponsored than industry-sponsored
      trials containing unambiguous POS discrepancies. POS discrepancies due to
      ambiguous reporting included vaguely worded PO registration; or failing to report
      the timing of PO assessment, statistical analysis used for the PO, or method to
      address missing PO data. At best, POS discrepancies may be attributable to
      insufficient registry requirements, carelessness (eg, failing to report PO
      assessment timing), or difficulty uploading registry information. At worst,
      discrepancies could indicate investigator impropriety (eg, registering imprecise
      PO ["pain"], then publishing whichever pain assessment produced statistically
      significant results). Improvements in PO registration, as well as journal
      policies requiring consistency between registered and published PO descriptions,
      are needed.

PMID- 23962591
TI  - Long-term complications associated with permanent dermal fillers.
AB  - We report a case series of patients with serious long-term complications
      associated with the injection of permanent dermal fillers. Although such
      complications are relatively rare, the consequences are potentially life-long,
      and the psychological and medical effects can often have a profound impact on the
      patient. The continued routine offering of these treatments will require doctors
      to communicate effectively with patients about the nature of the complications
      and the probability of risk compared with alternative treatments. 

PMID- 23962592
TI  - Visual assessment of the bond strength between an orthodontic bracket and an
      impacted maxillary canine: the "blue-needle" test.

PMID- 23962593
TI  - Efficacy of closed reduction for nasal fractures in children.
AB  - The aim of this study was to evaluate the efficacy of closed reduction and the
      effects of the time of intervention on young patients' satisfaction. Patients
      older than 16 years and those with additional maxillofacial fractures were
      excluded. All patients were treated by closed reduction and external fixation.
      The patients and parents were asked about their satisfaction in a survey 6
      months' postoperatively. They were divided into groups according to the time of
      intervention, and the results. Twenty-four patients, age range 4-16 years, with
      isolated nasal fractures were included in the study. The mean (SD) time before
      intervention was 5.5 (1.8) days. The first group comprised 16 patients whose
      fractures were reduced between days 1 and 5 after the injury, and the second the
      8 whose fractures were reduced between days 6 and 10. At 6 months 15 of the 24
      were satisfied with the result, and 9 were not. In the group treated between days
      1-5, 12/16 were happy with the result, and in the group treated between days 6
      10, 3/8 were satisfied. Closed reduction gives good results in the treatment of
      nasal fractures in children. Early intervention increases the rate of
      satisfaction. 

PMID- 23962594
TI  - Nationwide survey of surgically assisted rapid maxillary expansion.
AB  - We aimed to gather data on the current practice of surgically assisted rapid
      maxillary expansion (SARME) in the UK. Surveys were posted in the mail to all
      members of the British Association of Oral and Maxillofacial Surgeons (n=379) and
      166 (44%) responded. In the previous year 69 responders (42%) had done at least
      one SARME operation. The technique used by individual surgeons may be more
      experience-based than evidence-based, which leads to considerable variation. 

PMID- 23962595
TI  - Effectiveness of botulinum toxin B in the treatment of drooling.
AB  - The aim of this audit was to assess the effectiveness of botulinum toxin B
      (NeuroBloc((r)), Eisai Ltd.) in the treatment of drooling. Over a period of 18
      months patients treated with NeuroBloc((r)) botulinum toxin (BTX) for serious
      drooling (drooling score more than 7) were invited to complete a questionnaire on
      their experience of drooling and the impact of treatment. A total of 170
      questionnaires were given to consecutive patients or carers and 145 (85%)
      responded. Of these, 128 (88%) reported that symptoms had improved by 6/10 or
      more on a visual analogue scale (VAS), and 54 (37%) reported compete resolution
      of drooling (10/10 VAS). A total of 139 (96%) would recommend the treatment to
      others. 

PMID- 23962596
TI  - Measurement of functional heel pad behaviour in-shoe during gait using orthotic
      embedded ultrasonography.
AB  - The ability to measure the functional behaviour of the plantar heel pad is
      clinically relevant in dystrophic or pathological heel conditions and may help to
      inform the design and development of interventions that attempt to restore normal
      function. In this study we present a novel technique which utilises orthotic heel
      inserts with an embedded ultrasound (US) transducer to allow the functional,
      dynamic behaviour of the heel pad to be measured in-shoe during gait. The aim of
      this study was to demonstrate feasibility of the technique, determine the
      reproducibility of measurements, and to compare the effects of two orthotic
      inserts: (i) a flat orthotic heel raise and (ii) a contoured heel cup insert on
      the behaviour of the heel pad during gait. Dynamic compression of the heel pads
      of 16 healthy participants was recorded during treadmill walking and combined
      with plantar pressure measurements to allow stiffness and energy disappation
      ratio (EDR) to be estimated. Inter-session reliability of the US measurements was
      found to be excellent (ICC2,1=0.94-0.95), as was inter-rater reliability
      (ICC2,1=0.89). Use of the heel cup insert significantly reduced the maximum
      compression of the heel pad (p<0.0001) as well as the overall stiffness of the
      pad (p<0.001). There was no change in EDR (p=0.949). In-shoe embedded US is a
      reliable method to establish person-specific functional geometry of plantar soft
      tissues. Use of a contoured heel cup reduces the compression of the mid portion
      of the heel pad.

PMID- 23962597
TI  - Prevalence and molecular epidemiology of Staphylococcus aureus in Swedish nursing
      homes - as revealed in the SHADES study.
AB  - SUMMARY: Knowledge of carriage and population dynamics of Staphylococcus aureus
      is crucial for infection risk assessment and to reveal transmission patterns of
      strains. We report the prevalence and molecular epidemiology of S. aureus in
      elderly people (n = 290) living in nursing homes in three cities in the south of
      Sweden. The overall carriage prevalence rate was 48% when results from nares
      (31%) and throat (34%) samples were combined. Common spa types were equally
      distributed but a frequent type, t160, was found only in one of the regions.
      Carriage of different spa types was detected in 23% of individuals and
      antimicrobial resistance rates were higher in S. aureus isolates from those
      carrying more than one spa type. Five of the 21 individuals who carried different
      spa types were colonized simultaneously with resistant and non-resistant strains.
      Seventeen per cent of the individuals carried S. aureus of the same spa type on
      all occasions. Methicillin resistance was not detected. In conclusion we found a
      high prevalence of S. aureus in this elderly population with a high rate of dual
      colonization with different spa types. We also found signs of institutional
      spread of one strain.

PMID- 23962598
TI  - Bidirectionality and gender differences in emotional disturbance associations
      with obesity among Taiwanese schoolchildren.
AB  - Childhood obesity is associated with psychological problems, but little is known
      about its association with emotional disturbance (ED) in the educational setting,
      especially by gender. In the population representative Elementary School
      Children's Nutrition and Health Survey in Taiwan 2001-2002 of children aged 6-13
      (n=2283), we have considered whether ED is associated with obesity by gender.
      Schoolchildren were assessed with the modified scale for assessing emotional
      disturbance questionnaires. For some subscales, boys and girls had ED
      associations with obesity which were bidirectional. With normal weight as
      referent and relevant adjustments, the significant ED subscales predictable by
      obesity were relationship problems (RP) in boys (odds ratio, OR=1.89 with 95% CI:
      1.08-3.30) and inappropriate behavior (IB) in girls (OR=2.88: 95% CI: 1.47-5.61).
      Conversely, with 'no-specific-ED' as referent, obesity was predictable by fully
      adjusted specific-EDs in the same subscales, namely RP in boys (OR=1.88 with 95%
      CI: 1.13-3.13) and IB in girls (OR=3.03: 95% CI: 1.57-5.85). Child obesity
      prevalence showed no trend with school grade from 1 to 6, but for aggregate ED
      and most of its subscales the prevalence increased with grade (P for trend
      <0.01). Thus, there is some dissociation of obesity and ED as judged by their
      trend presence with school grade. Where obesity and ED occurred together (for
      inability-to-learn and unhappiness or depression), there were upward trends with
      grade (P<0.01). There are probably some selected bidirectional pathogenicities
      for obesity-ED associations with different expression in boys and girls and
      during elementary education. This provides some policy direction while mechanisms
      and causality require elucidation. 

PMID- 23962599
TI  - The influence of dual-task conditions on movement in young adults with and
      without Down syndrome.
AB  - This investigation compared spatial and temporal movement parameters of a sample
      of young adults with Down syndrome (DS) (N=12) and individuals without
      disabilities (IWD) (N=12) under dual-task conditions. Subjects performed a
      walking task at a preferred speed in isolation and again while holding a plate
      and cup, carrying tray and cups, talking on a phone, or buttoning a shirt.
      Spatial and temporal values were compared using a 2 (group) * 5 (conditions)
      repeated measures analysis of variance. Analysis of spatial components separately
      indicated that step length, step width, stride length and stride width revealed
      significant group and condition interactions (p <=.01). Temporal components
      yielded significance in velocity and single-leg support time (p <=.01). The
      current results support the notion that along with impairments to qualitative
      motor skills, individuals with DS are also impaired in higher order executive
      functioning (EF), as measured by a dual-task paradigm. It was concluded that
      movements are less efficient and functional in individuals with DS when an
      additional task is encountered while walking. We theorized that the motor program
      was sufficient for general locomotion but was not sufficiently developed to allow
      individuals with DS to modify or alter their movements to changing cognitive
      conditions that increasingly taxed EF. As gait and balance are trainable in this
      population, we recommend developing appropriate exercise and motor skill
      interventions during childhood and adolescents to increase strength, stability,
      and more "robust" ambulatory motor schema.

PMID- 23962600
TI  - Development of a Mandarin Expressive and Receptive Vocabulary Test for children
      using cochlear implants.
AB  - Cochlear implants (CIs) provide children with profound hearing loss access to
      sounds and speech. Research on the effects of CI on speech and language
      development in mainland China is scarce due to the lack of standardized tests.
      This study aims at developing a vocabulary measure, the Mandarin Expressive and
      Receptive Vocabulary Test (MERVT), for pre-school children with CIs. Using
      responses from 102 normal-hearing preschool children, the initial vocabulary set
      was subjected to analyses to identify items with appropriate levels of difficulty
      and discrimination. Norms on 245 normal-hearing children aged 1;6 to 3;11 were
      later collected based on the final set of the items. Evaluation of the test's
      psychometric properties revealed good internal consistency. Significant
      correlations between the total MERVT scores and the Gesell Developmental Scale
      scores, between the MERVT expressive and receptive subtest scores and the total
      scores, and the gradual increase in MERVT scores with age, provided evidence of
      construct validity. Results from 29 children with CIs were also examined for
      evidence of the MERVT's construct validity. There was a significant correlation
      between these children's MERVT scores and their scores from an intelligence test.
      The MERVT scores increased with an increase in the duration of CI use and in
      chronological age. With good reliability and strong validity, the test is
      recommended for use in the monitoring of language development in children with
      CI. 

PMID- 23962601
TI  - Adults' preferences between Picture Communication Symbols (PCSs) and Gus
      Communication Symbols (GCSs) used in AAC.
AB  - The purpose of the study was to determine whether significantly different
      preference exists in typical adults between Picture Communication Symbols (PCSs)
      and Gus Communication Symbols (GCSs) frequently displayed on their AAC. A total
      of 56 participants participated in the study, including 15 participants in ages
      20-35; 14 participants in ages 36-50; 13 participants in ages 51-60; and 14
      participants in ages 66-80. Two tasks, an identification task and a preference
      task, were administered sequentially and individually. The results of this study
      suggest: (1) typical adults' preference between PCSs and GCSs did not show any
      significant difference; (2) the effect of age groups of typical adults did not
      have any significant effect on their preference between PCSs and GCSs. However,
      except the group of ages 51-65, the other three groups did consciously show their
      preferences for PCSs. Limitations and clinical implications of the current study
      have been concluded. 

PMID- 23962602
TI  - The development of a multimedia online language assessment tool for young
      children with autism.
AB  - This study aimed to provide early childhood special education professionals with
      a standardized and comprehensive language assessment tool for the early
      identification of language learning characteristics (e.g., hyperlexia) of young
      children with autism. In this study, we used computer technology to develop a
      multi-media online language assessment tool that presents auditory or visual
      stimuli. This online comprehensive language assessment consists of six subtests:
      decoding, homographs, auditory vocabulary comprehension, visual vocabulary
      comprehension, auditory sentence comprehension, and visual sentence
      comprehension. Three hundred typically developing children and 35 children with
      autism from Tao-Yuan County in Taiwan aged 4-6 participated in this study. The
      Cronbach alpha values of the six subtests ranged from .64 to .97. The variance
      explained by the six subtests ranged from 14% to 56%, the current validity of
      each subtest with the Peabody Picture Vocabulary Test-Revised ranged from .21 to
      .45, and the predictive validity of each subtest with WISC-III ranged from .47 to
      .75. This assessment tool was also found to be able to accurately differentiate
      children with autism up to 92%. These results indicate that this assessment tool
      has both adequate reliability and validity. Additionally, 35 children with autism
      have completed the entire assessment in this study without exhibiting any
      extremely troubling behaviors. However, future research is needed to increase the
      sample size of both typically developing children and young children with autism
      and to overcome the technical challenges associated with internet issues. 

PMID- 23962603
TI  - Systematic review of self-concept measures for primary school aged children with
      cerebral palsy.
AB  - This study involved a systematic review aimed to identify self-concept measures
      that provided published psychometrics for primary school aged children (8-12
      years) with cerebral palsy (CP). Six electronic databases (PubMed, MEDLINE,
      CINAHL, PsycINFO, PsycARTICLES and Web of Science) were searched to identify
      assessments that (1) measured self-concept; (2) in children aged 8-12 years; (3)
      with CP; (4) with psychometrics available. The Consensus-based Standards for the
      Selection of Health Measurement Instruments (COSMIN) checklist was used to
      evaluate psychometric properties and the CanChild Outcome Measure Rating Form was
      used to evaluate clinical utility. Search yielded 271 papers, of which five met
      inclusion criteria. These papers reported five measures of self-concept with
      psychometric properties for the target population: the Rosenberg Self-Esteem
      Index, Self-Description Questionnaire-I, Self-Perception Profile for Children
      (original) and two separate modifications of the Self-Perception Profile for
      Children. Currently, no self-concept measures published in English had sufficient
      psychometric data for children with CP. The Self-Description Questionnaire-I and
      the Self-Perception Profile for Children were promising options. Further research
      is required (a) to determine self-concept construct components important for
      children with CP and (b) to examine the relative strength, validity, reliability
      and clinical utility of self-concept measures for the target population. 

PMID- 23962604
TI  - The Self- and Other-Deception Questionnaires-Intellectual Disabilities (SDQ-ID
      and ODQ-ID): component analysis and reliability.
AB  - The objectives of this research were to: (1) investigate the component structure
      and psychometric properties of the Self- and Other-Deception Questionnaires
      Intellectual Disabilities (SDQ-ID and ODQ-ID), (2) examine the relationship
      between social desirability and IQ, and (3) compare social desirability scores of
      those with intellectual disabilities (IDs) and a history of criminal offending to
      the social desirability scores of participants with IDs and those without IDs and
      no such history, controlling for general intellectual functioning. Men with mild
      to borderline IDs detained within medium secure inpatient forensic mental health
      services (N=40) completed the SDQ-ID and ODQ-ID at Time 1 and then two-weeks
      later at Time 2. Data for the men with and without IDs and no known criminal
      offending history were taken from a previous study (N=60). Following exploratory
      Principal Components Analysis, the number of questionnaire items were reduced,
      and a two-factor structure was found for the SDQ-ID which was labelled: (1)
      Positive Self Representation and (2) Denial of Intrusive Thoughts. A two-factor
      structure was also found for the ODQ-ID and these two factors were labelled: (1)
      Denial of Negative Social Interaction and (2) Untrustworthiness. Both the SDQ-ID
      and ODQ-ID had acceptable internal consistency and test-retest reliability.
      Fifteen percent of the variance in SDQ-ID scores was explained by Full Scale IQ,
      while 21% of the variance in ODQ-ID scores was explained by Full Scale IQ.
      Between group comparisons controlling for intelligence did not yield any
      significant differences. The shortened SDQ-ID and ODQ-ID have promising
      psychometric properties, and their component structures appear robust.
      Differences between men with and without IDs on these two measures of social
      desirability can be accounted for by differences in general intellectual
      functioning. 

PMID- 23962605
TI  - Executive control in long-term abstinent alcoholics with mild to borderline
      intellectual disability: the relationship with IQ and severity of alcohol use
      related problems.
AB  - Deficits in executive control might be related to alcohol abuse in individuals
      with mild to borderline intellectual disability (MBID). The goal of the present
      study was to test the relationship between executive control (i.e., working
      memory capacity, inhibitory control and delay discounting), IQ and chronic
      alcohol use. Participants (N=40) were divided into four groups based on IQ and
      severity of alcohol use-related problems (heavy and light drinkers with and
      without MBID). They were all admitted to a psychiatric treatment facility and
      long-term abstinent at the time of testing. Contrary to the expectations,
      executive control was not consistently impaired among individuals with MBID.
      Results showed that working memory capacity did seem to be impaired, whereas
      inhibitory control and delay discounting did not. Moreover, there were no
      differences between heavy and light drinkers on any of the parameters and having
      a dual diagnosis (heavy drinkers with MBID) did not result in additive negative
      effects on executive control. It is suggested that alcohol-related cognitive
      impairment is temporary and decreases over time after cessation of drinking. 

PMID- 23962606
TI  - Disability as a risk factor? Development of psychopathology in children with
      disabilities.
AB  - Empirical research has established that children with disabilities are more
      likely to develop psychopathology than children without disabilities. But too
      little is known about the association between disability and psychopathology. The
      aim of this article is to discuss developmental psychopathological models that
      conceptualise the connection between childhood disability and psychopathology.
      Empirical studies of psychopathology among children with a congenital hearing
      impairment and children with cerebral palsy will be reviewed, representing in
      depth examples of association between disability and psychopathology. Both a
      congenital hearing impairment and cerebral palsy were found to be dominating risk
      factors for all types of psychopathology, but no relationship was identified
      between degree of disability and risk of psychopathology. The higher risk cannot
      be explained by biological impairments alone. To explain the contradictory
      findings, developmental models of disability and psychopathology are applied.
      Within a multi-factorial developmental psychopathological perspective and a
      dialectical model of disability (Vygotsky, 1993), it is suggested that disability
      can be understood as an incongruence between the individual development of the
      child and demands and expectations in the specific relations and institutions in
      which the child participates. This incongruence creates and strengthens negative
      factors for the child with disability and results in a higher risk of
      psychopathology. 

PMID- 23962607
TI  - Identifying emerging trends for implementing learning technology in special
      education: a state-of-the-art review of selected articles published in 2008-2012.
AB  - As electronic learning (e-learning) becomes increasingly popular in education
      worldwide, learning technology (LT) has been applied in various learning
      environments and activities to promote meaningful, efficient, and effective
      learning. LT has also been adopted by researchers and teacher-practitioners in
      the field of special education, but as yet little review-based research has been
      published. This review research thus carefully examined the trends of LT
      implementations in special education, providing a comprehensive analysis of 26
      studies published in indexed journals in the past five years (2008-2012). Two
      research questions were addressed: (a) What are the major research aims,
      methodologies, and outcomes in these studies of implementing LT in the field of
      special education? and (b) What types of LT are mainly used with special
      education students, and for what kinds of students? Major findings include that
      examining the learning effectiveness of LT using was the most common research
      purpose (75%); researchers primarily relied on experimental studies (46%, 12
      studies), followed by interviews and questionnaires (19%, 5 studies). Moreover,
      the most common use of LT was computer-assisted technology (such as web-based
      mentoring, educational computer games, laptop computers) in special education;
      studies investigating the use of LT with mentally disabled students were more
      than those with physically disabled ones. It is expected that the findings of
      this work and their implications will serve as valuable references with regard to
      the use of LT with special education students. 

PMID- 23962608
TI  - EUROMCONTACT.

PMID- 23962609
TI  - Translational research in primary mitochondrial diseases: challenges and
      opportunities.
AB  - On March 8-9, 2012, the NIH intramural and extramural research communities as
      well as representatives from industries and foundations with a common interest in
      primary mitochondrial diseases met in Bethesda to identify the major barriers to
      the development of better treatment for mitochondrial diseases. Besides the
      importance to the patient population, it has become clear in the last decade that
      advances in understanding and treating primary mitochondrial diseases will impact
      research into a large number of degenerative conditions known to have a
      significant mitochondrial dysfunction component in their pathogenic mechanisms
      (secondary mitochondrial diseases) that affect millions of people, including
      Alzheimer's disease, Parkinson's disease,diabetes, ALS, autism spectrum
      disorders, and many others. We would like to make this discussion available to
      the scientific community, as it provides a framework on how patient advocacy
      groups, individual academic units, pharmaceutical companies, and the NIH can
      interact to address problems related to mitochondrial diseases.The main goals of
      this workshop were as follows: (1) to share information related to primary
      mitochondrial disease among the NIH Intramural and Extramural Research Program
      Investigators, (2) to develop and/or enhance systems to facilitate future
      collaboration and sharing of information, (3) to survey obstacles, needs and
      priorities of primary mitochondrial diseases research, and (4) to develop
      mechanisms to enhance translation of basic science discoveries to diagnostics and
      therapeutics.

PMID- 23962610
TI  - Ovarian cancers arising from endometriosis: a microenvironmental biomarker study
      including ER, HNF1beta, p53, PTEN, BAF250a, and COX-2.
AB  - BACKGROUND: The microenvironmental biomarkers of different subtypes of ovarian
      cancers arising from endometriosis have not been studied in Taiwan. Their
      expression can help in understanding the carcinogenic mechanism. METHODS: Our
      study used immunohistochemistry to compare the expression of estrogen receptor
      (ER), hepatocyte nuclear factor-1 beta (HNF1beta), p53, phosphatase and tensin
      homolog (PTEN), BAF250a, and cyclooxygenase-2 (COX-2) among 79 cases of
      endometriosis-associated ovarian cancers, including 40 (50%) clear cell
      carcinomas (CCCs), 33 (41%) endometrioid (EM) adenocarcinomas, four (5%) serous
      carcinomas, one adenosquamous carcinoma, and one adenosarcoma. RESULTS: Positive
      stainings for ER, HNF1beta, p53, and COX-2 were identified in 34 (43%), 30 (38%),
      10 (13%), and 44 (56%) cases. Loss of PTEN and BAF250a were noted in 29 (37%) and
      37 (47%) cases. The expression of ER was reversely correlated with that of
      HNF1beta (rho = -0.417, p < 0.001) and correlated with p53 (rho = 0.284, p =
      0.011). ER positivity was commonly identified in EM adenocarcinomas (91%), and
      rarely in CCCs (8%) and serous carcinoma (0%; p < 0.001). By contrast, HNF1beta
      expression was frequently noted in CCCs (65%) and serous carcinomas (50%), but
      less in EM adenocarcinoma (6%; p < 0.001). All staining results were similar
      between atypical endometriosis glandular epithelium and contiguous malignant
      parts. Only nine cases showed 10 minor differences (10/474, 2%) in ER, HNF1beta,
      and BAF250a. For the staining patterns of p53, COX-2, and PTEN, there was no
      difference between the invasive and precursor parts. CONCLUSION: Our results
      supported the suggestion that estrogen-dependent ovarian cancer arising from
      endometriosis is substantially more associated with EM adenocarcinoma than CCCs.
      The positive HNF1beta staining was a frequent finding in CCCs, but not in EM
      adenocarcinoma. The similar staining patterns of atypical endometriosis glandular
      cells with the invasive parts confirmed their precursor status.

PMID- 23962612
TI  - Will he walk again? Only Dr. Nociception knows!

PMID- 23962611
TI  - Identification of Borrelia burgdorferi ospC genotypes in canine tissue following
      tick infestation: implications for Lyme disease vaccine and diagnostic assay
      design.
AB  - In endemic regions, Lyme disease is a potential health threat to dogs. Canine
      Lyme disease manifests with arthritis-induced lameness, anorexia, fever,
      lethargy, lymphadenopathy and, in some cases, fatal glomerulonephritis. A recent
      study revealed that the regional mean for the percentage of seropositive dogs in
      the north-east of the USA is 11.6%. The outer surface protein C (OspC) of Lyme
      disease spirochetes is an important virulence factor required for the
      establishment of infection in mammals. It is a leading candidate in human and
      canine Lyme disease vaccine development efforts. Over 30 distinct ospC phyletic
      types have been defined. It has been hypothesized that ospC genotype may
      influence mammalian host range. In this study, Ixodes scapularis ticks collected
      from the field in Rhode Island were assessed for infection with B. burgdorferi.
      Ticks were fed on purpose bred beagles to repletion and infection of the dogs was
      assessed through serology and PCR. Tissue biopsies (n=2) were collected from each
      dog 49 days post-tick infestation (dpi) and the ospC genotype of the infecting
      strains determined by direct PCR of DNA extracted from tissue or by PCR after
      cultivation of spirochetes from biopsy samples. The dominant ospC types
      associated with B. burgdorferi canine infections differed from those associated
      with human infection, indicating a relationship between ospC sequence and
      preferred host range. Knowledge of the most common ospC genotypes associated
      specifically with infection of dogs will facilitate the rational design of OspC
      based canine Lyme disease vaccines and diagnostic assays.

PMID- 23962613
TI  - The antimicrobial activity of honey against common equine wound bacterial
      isolates.
AB  - Delayed healing associated with distal limb wounds is a particular problem in
      equine clinical practice. Recent studies in human beings and other species have
      demonstrated the beneficial wound healing properties of honey, and medical grade
      honey dressings are available commercially in equine practice. Equine clinicians
      are reported to source other non-medical grade honeys for the same purpose. This
      study aimed to assess the antimicrobial activity of a number of honey types
      against common equine wound bacterial pathogens. Twenty-nine honey products were
      sourced, including gamma-irradiated and non-irradiated commercial medical grade
      honeys, supermarket honeys, and honeys from local beekeepers. To exclude
      contaminated honeys from the project, all honeys were cultured aerobically for
      evidence of bacterial contamination. Aerobic bacteria or fungi were recovered
      from 18 products. The antimicrobial activity of the remaining 11 products was
      assessed against 10 wound bacteria, recovered from the wounds of horses,
      including methicillin resistant Staphylococcus aureus and Pseudomonas aeruginosa.
      Eight products were effective against all 10 bacterial isolates at concentrations
      varying from <2% to 16% (v/v). Overall, the Scottish Heather Honey was the best
      performing product, and inhibited the growth of all 10 bacterial isolates at
      concentrations ranging from <2% to 6% (v/v). Although Manuka has been the most
      studied honey to date, other sources may have valuable antimicrobial properties.
      Since some honeys were found to be contaminated with aerobic bacteria or fungi,
      non-sterile honeys may not be suitable for wound treatment. Further assessment of
      gamma-irradiated honeys from the best performing honeys would be useful. 

PMID- 23962614
TI  - Determination of genomic copy number alteration emphasizing a restriction site
      based strategy of genome re-sequencing.
AB  - MOTIVATION: Copy number abbreviation (CNA) is one type of genomic aberration that
      is often induced by genome instability and is associated with diseases such as
      cancer. Determination of the genome-wide CNA profile is an important step in
      identifying the underlying mutation mechanisms. Genomic data based on next
      generation sequencing technology are particularly suitable for determination of
      high-quality CNA profile. Now is an important time to reevaluate the use of
      sequencing techniques for CNA analysis, especially with the rapid growth of the
      different targeted genome and whole-genome sequencing strategies. RESULTS: In
      this study, we provide a comparison of resequencing strategies, with regard to
      their utility, applied to the same hepatocellular carcinoma sample for copy
      number determination. These strategies include whole-genome, exome and
      restriction site-associated DNA (RAD) sequencing. The last of these strategies is
      a targeted sequencing technique that involves cutting the genome with a
      restriction enzyme and isolating the targeted sequences. Our data demonstrate
      that RAD sequencing is an efficient and comprehensive strategy that allows the
      cost-effective determination of CNAs. Further investigation of RAD sequencing
      data led to the finding that a precise measurement of the allele frequency would
      be a helpful complement to the read depth for CNA analysis for two reasons.
      First, knowledge of the allele frequency helps to resolve refined calculations of
      allele-specific copy numbers, which, in turn, identify the functionally important
      CNAs that are under natural selection on the parental alleles. Second, this
      knowledge enables deconvolution of CNA patterns in complex genomic regions.

PMID- 23962615
TI  - fmcsR: mismatch tolerant maximum common substructure searching in R.
AB  - MOTIVATION: The ability to accurately measure structural similarities among small
      molecules is important for many analysis routines in drug discovery and chemical
      genomics. Algorithms used for this purpose include fragment-based fingerprint and
      graph-based maximum common substructure (MCS) methods. MCS approaches provide one
      of the most accurate similarity measures. However, their rigid matching policies
      limit them to the identification of perfect MCSs. To eliminate this restriction,
      we introduce a new mismatch tolerant search method for identifying flexible MCSs
      (FMCSs) containing a user-definable number of atom and/or bond mismatches.
      RESULTS: The fmcsR package provides an R interface, with the time-consuming steps
      of the FMCS algorithm implemented in C++. It includes utilities for pairwise
      compound comparisons, structure similarity searching, clustering and
      visualization of MCSs. In comparison with an existing MCS tool, fmcsR shows
      better time performance over a wide range of compound sizes. When mismatching of
      atoms or bonds is turned on, the compute times increase as expected, and the
      resulting FMCSs are often substantially larger than their strict MCS
      counterparts. Based on extensive virtual screening (VS) tests, the flexible
      matching feature enhances the enrichment of active structures at the top of MCS
      based similarity search results. With respect to overall and early enrichment
      performance, FMCS outperforms most of the seven other VS methods considered in
      these tests. AVAILABILITY: fmcsR is freely available for all common operating
      systems from the Bioconductor site
      (http://www.bioconductor.org/packages/devel/bioc/html/fmcsR.html). CONTACT:
      thomas.girke@ucr.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available
      at Bioinformatics online.

PMID- 23962616
TI  - ProteoStats--a library for estimating false discovery rates in proteomics
      pipelines.
AB  - SUMMARY: Statistical validation of peptide assignments from a large-scale shotgun
      proteomics experiment is a critical step, and various methods for evaluating
      significance based on decoy database search are in practice. False discovery rate
      (FDR) estimation of peptide assignments assesses global significance and corrects
      for multiple comparisons. Various approaches have been proposed for FDR
      estimation but unavailability of standard tools or libraries leads to development
      of many in-house scripts followed by manual steps that are error-prone and low
      throughput. The ProteoStats library provides an open-source framework for
      developers with many FDR estimation and visualization features for several
      popular search algorithms. It also provides accurate q-values, which can be
      easily integrated in any proteomics pipeline to provide automated, accurate, high
      throughput statistical validation and minimize manual errors. AVAILABILITY:
      https://sourceforge.net/projects/mssuite/files/ProteoStats/. CONTACT:
      ddash@igib.res.in or aky.compbio@gmail.com or amit.yadav@igib.in. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 23962617
TI  - Accurate identification of polyadenylation sites from 3' end deep sequencing
      using a naive Bayes classifier.
AB  - MOTIVATION: 3' end processing is important for transcription termination, mRNA
      stability and regulation of gene expression. To identify 3' ends, most techniques
      use an oligo-dT primer to construct deep sequencing libraries. However, this
      approach can lead to identification of artifactual polyadenylation sites due to
      internal priming in homopolymeric stretches of adenines. Although heuristic
      filters have been applied in these cases, they typically result in a high
      proportion of both false-positive and -negative classifications. Therefore, there
      is a need to develop improved algorithms to better identify mis-priming events in
      oligo-dT primed sequences. RESULTS: By analyzing sequence features flanking 3'
      ends derived from oligo-dT-based sequencing, we developed a naive Bayes
      classifier to classify them as true or false/internally primed. The resulting
      algorithm is highly accurate, outperforms previous heuristic filters and
      facilitates identification of novel polyadenylation sites.

PMID- 23962618
TI  - Digit span: a comparison of Chinese versus alphabetic language speakers in
      dysexecutive dementia patients.

PMID- 23962619
TI  - Is the 'liberation procedure' for multiple sclerosis really liberating?

PMID- 23962620
TI  - Seizures after craniectomy: an under-recognised complication?

PMID- 23962621
TI  - Identification and expression analysis of a novel R-type lectin from the
      coleopteran beetle, Tenebrio molitor.
AB  - We have identified novel ricin-type (R-type) lectin by sequencing of random
      clones from cDNA library of the coleopteran beetle, Tenebrio molitor. The cDNA
      sequence is comprised of 495 bp encoding a protein of 164 amino acid residues and
      shows 49% identity with galectin of Tribolium castaneum. Bioinformatics analysis
      shows that the amino acid residues from 35 to 162 belong to ricin-type beta
      trefoil structure. The transcript was significantly upregulated after early hours
      of injection with peptidoglycans derived from Gram (+) and Gram (-) bacteria,
      beta-1, 3 glucan from fungi and an intracellular pathogen, Listeria monocytogenes
      suggesting putative function in innate immunity.

PMID- 23962622
TI  - Characterization of plasma cholinesterase from the White stork (Ciconia ciconia)
      and its in vitro inhibition by anticholinesterase pesticides.
AB  - Blood plasma cholinesterase (ChE) activity is a sensitive biomarker of exposure
      to organophosphorus (OP) and carbamate (CB) insecticides in vertebrates. Several
      studies indicate that more than one ChE form may be present in blood of birds. In
      this study the predominant ChE activity (acetylcholinesterase - AChE- or
      butyrylcholinesterase - BChE-), the range of ChE activity as well as ChE age
      dependent changes in non-exposed individuals of White stork (Ciconia ciconia)
      have been established. The in vitro sensitivity of ChE to OP and CB insecticides
      such as paraoxon-methyl, carbofuran and carbaryl was also investigated. Plasma
      ChE was characterised using three substrates (acetylthiocholine iodide,
      propionylthiocholine iodide, and S-butyrylthiocholine iodide) and three ChE
      inhibitors (eserine sulphate, BW284C51 and iso-OMPA). The results indicated that
      propionylthiocholine was the preferred substrate by plasma cholinesterase
      followed by acetylcholine and butyrylcholine and the predominant enzymatic
      activity in plasma of White storks was BChE. Normal plasma BChE activity in White
      stork was 0.32+/-0.01MUmol/min/ml for adults and 0.28+/-0.03MUmol/min/ml for
      juveniles. So, the age had no significant effect on the range of BChE activity.
      The study on the in vitro inhibitory potential of tested anticholinesterase
      pesticides on plasma ChE activity revealed that paraoxon-methyl is the most
      potent inhibitor followed by carbofuran and finally by carbaryl. The percentage
      of in vitro plasma ChE inhibition was observed to be similar between adults and
      juveniles. 

PMID- 23962624
TI  - Normative values for the Bath Ankylosing Spondylitis Metrology Index in a UK
      population.
AB  - OBJECTIVE: Spinal mobility is assessed frequently in patients with AS/axial SpA
      using the BASMI to provide baseline measurement and monitor change over time. The
      interpretation of BASMI scores has been hindered by the absence of normative
      values. We aimed to obtain normative values for the BASMI in healthy men and
      women in a UK population. METHODS: A cross-sectional study of 168 volunteers
      stratified by gender and age was completed. Exclusion criteria comprised factors
      potentially influencing spinal mobility. Each component of the BASMI was
      assessed, with the total score computed using the 10-point scoring system.
      Measurements were taken by physiotherapists following an agreed protocol. Data
      were summarized and analysed with age-specific centiles and CIs calculated.
      RESULTS: Total BASMI scores ranged from 0 to 4.4, with only 1.2% of the sample
      having a score of 0. The estimated median score for an individual age 25 years
      was 0.9, increasing with age to 2.1 for an individual age 65 years. There was a
      corresponding increase in component BASMI scores, which was more pronounced for
      some components than others. CONCLUSION: Our data indicate that it is unusual for
      healthy individuals to score zero on the BASMI, which has implications for the
      interpretation of scores, especially at baseline. The generation of normative
      values has the potential to inform clinical assessment of spinal mobility and
      assist patients in understanding how their spinal mobility compares with that of
      a healthy age-matched population.

PMID- 23962623
TI  - PEGylated drugs in rheumatology--why develop them and do they work?
AB  - Lack of efficacy and drug-related adverse effects are important reasons for the
      discontinuation of treatment in patients with rheumatic diseases. The development
      of new biologic therapies seeks to address these problems by specifically
      targeting the pathogenic mechanisms of disease. Most current biologics are
      proteins (particularly antibodies and enzymes) administered parenterally. It is
      important to optimize properties such as serum half-life, immunogenicity and
      solubility. Companies have thus begun to modify the drugs by conjugate chemistry,
      binding inert molecules such as polyethylene glycol (PEG) to biologic molecules
      to improve their pharmacodynamic properties. The use of PEG to alter these
      properties has to be weighed against the negative aspects of PEGylation, such as
      decreased activity and heterogeneity. This review focuses on the currently
      available PEGylated drugs used in rheumatological diseases, their efficacy,
      drawbacks and the current clinical trial evidence supporting their use. 

PMID- 23962625
TI  - A parallel group cohort to determine the measurement properties of an early
      inflammatory arthritis detection tool.
AB  - OBJECTIVES: To determine the comprehensibility, internal consistency, test-retest
      reliability and discriminative properties of an early inflammatory arthritis (IA)
      detection tool. METHODS: Four groups were recruited from outpatient clinics at
      two tertiary care hospitals: early IA, established IA, non-IA musculoskeletal
      conditions (MSK) and non-MSK. Participants attended a study visit where they
      completed the 11-item tool with binary yes/no response options. Comprehensibility
      was assessed for each tool item on a 5-point Likert scale. For test-retest
      assessment, the tool was mailed to participants following a 2-week recall washout
      interval. Two items were randomly selected to test internal consistency.
      Discriminative properties compared tool item responses with blinded
      rheumatologist clinical assessments. A previously developed rheumatology triage
      algorithm was externally validated. RESULTS: A total of 170 participants were
      enrolled in the study. Comprehensibility approached unity for all tool items. The
      internal consistency Kuder-Richardson Formula 20 was 0.985 (P < 0.0001). The mean
      test-retest reliability kappa (S.D.) was 0.81 (0.02). The intraclass correlation
      coefficient (ICC) (95% CI) for summed yes responses between test and retest
      phases was 0.94 (0.93, 0.95) and for algorithm scores was 0.97 (0.96, 0.98).
      Patient responses were significantly associated with the corresponding clinical
      evaluations (P < 0.0001, respectively). The sum of yes responses and rheumatology
      triage algorithm scores both differentiated early IA from each of the other three
      groups (P < 0.004, respectively). The scoring algorithm receiver operating
      characteristic plot area under the curve (S.E.) was 0.829 (0.003). CONCLUSION:
      The tool has favourable measurement and discriminative properties. The
      discriminative properties of the rheumatology triage scoring algorithm were
      externally validated.

PMID- 23962626
TI  - Efficacy and tolerability of repeated cycles of a once-weekly regimen of
      bortezomib in lupus.

PMID- 23962627
TI  - Sex differences in jealousy: a population-based twin study in Sweden.
AB  - According to the theory of evolved sex differences in jealousy, the challenge for
      women to ensure paternal investment increased their jealousy response to
      emotional infidelity, whereas paternal uncertainty exerted selective pressures
      that shaped men to become more distressed by sexual infidelity. Several studies
      have investigated whether the effect of these sexually dimorphic selection
      pressures can be detected in contemporary human populations, with conflicting
      results. To date, no genetically informed studies of sex differences in jealousy
      have been conducted. We used data from the Screening Across the Lifespan of Twins
      Younger (SALTY) sample, containing information concerning self-rated jealousy
      from 3,197 complete twin pairs collected by the Swedish Twin Registry. Intra
      class correlations and structural equation models were used to assess the genetic
      influence on jealousy and to investigate sex differences at genetic level. We saw
      a highly significant sex effect on the relationship between infidelity types,
      indicating that men, relative to women, reported greater jealousy in response to
      sexual infidelity than in response to emotional infidelity. The twin models
      revealed significant heritabilities for both sexual (32%) and emotional (26%)
      jealousy. The heritabilities were of a similar magnitude in both sexes, and no
      qualitative sex differences could be detected. We show for the first time that
      variance in jealousy is to some extent explained by genetic factors. Even though
      our results from the mean value analyses are in line with the theory of evolved
      sex differences in jealousy, we could not identify any sex differences on a
      genetic level. 

PMID- 23962628
TI  - Expanding the paradigm of thiol redox in the thermophilic root of life.
AB  - BACKGROUND: The current paradigm of intracellular redox chemistry maintains that
      cells establish a reducing environment maintained by a pool of small molecule and
      protein thiol to protect against oxidative damage. This strategy is conserved in
      mesophilic organisms from all domains of life, but has been confounded in
      thermophilic organisms where evidence suggests that intracellular proteins have
      abundant disulfides. METHODS: Chemical labeling and 2-dimensional gel
      electrophoresis were used to capture disulfide bonding in the proteome of the
      model thermophile Sulfolobus solfataricus. The redox poise of the metabolome was
      characterized using both chemical labeling and untargeted liquid chromatography
      mass spectrometry. Gene annotation was undertaken using support vector machine
      based pattern recognition. RESULTS: Proteomic analysis indicated the
      intracellular protein thiol of S. solfataricus was primarily in the disulfide
      form. Metabolic characterization revealed a lack of reduced small molecule thiol.
      Glutathione was found primarily in the oxidized state (GSSG), at relatively low
      concentration. Combined with genetic analysis, this evidence shows that pathways
      for synthesis of glutathione do exist in the archaeal domain. CONCLUSIONS: In
      observed thermophilic organisms, thiol abundance and redox poise suggest that
      this system is not directly utilized for protection against oxidative damage.
      Instead, a more oxidized intracellular environment promotes disulfide bonding, a
      critical adaptation for protein thermostability. GENERAL SIGNIFICANCE: Based on
      the placement of thermophilic archaea close to the last universal common ancestor
      in rRNA phylogenies, we hypothesize that thiol-based redox systems are derived
      from metabolic pathways originally tasked with promoting protein stability.

PMID- 23962629
TI  - Interplay between autophagy and apoptosis mediated by copper oxide nanoparticles
      in human breast cancer cells MCF7.
AB  - BACKGROUND: Metal oxide nanoparticles are well known to generate oxidative stress
      and deregulate normal cellular activities. Among these, transition metals copper
      oxide nanoparticles (CuO NPs) are more compelling than others and able to
      modulate different cellular responses. METHODS: In this work, we have synthesized
      and characterized CuO NPs by various biophysical methods. These CuO NPs (~30nm)
      induce autophagy in human breast cancer cell line, MCF7 in a time- and dose
      dependent manner. Cellular autophagy was tested by MDC staining, induction of
      green fluorescent protein-light chain 3 (GFP-LC3B) foci by confocal microscopy,
      transfection of pBABE-puro mCherry-EGFP-LC3B plasmid and Western blotting of
      autophagy marker proteins LC3B, beclin1 and ATG5. Further, inhibition of
      autophagy by 3-MA decreased LD50 doses of CuO NPs. Such cell death was associated
      with the induction of apoptosis as revealed by FACS analysis, cleavage of PARP,
      de-phosphorylation of Bad and increased cleavage product of caspase 3. siRNA
      mediated inhibition of autophagy related gene beclin1 also demonstrated similar
      results. Finally induction of apoptosis by 3-MA in CuO NP treated cells was
      observed by TEM. RESULTS: This study indicates that CuO NPs are a potent inducer
      of autophagy which may be a cellular defense against the CuO NP mediated toxicity
      and inhibition of autophagy switches the cellular response into apoptosis.
      CONCLUSIONS: A combination of CuO NPs with the autophagy inhibitor is essential
      to induce apoptosis in breast cancer cells. GENERAL SIGNIFICANCE: CuO NP induced
      autophagy is a survival strategy of MCF7 cells and inhibition of autophagy
      renders cellular fate to apoptosis.

PMID- 23962630
TI  - Pathogenic compound heterozygous ATP7B mutations with hypoceruloplasminaemia
      without clinical features of Wilson's disease.
AB  - The authors report a 44-year-old man with a history of attention deficit and
      hyperactivity disorder, obsessive compulsive behaviour, vocal tics, depression,
      and anxiety, in whom a compound heterozygous ATP7B mutation was found, associated
      with hypoceruloplasminemia, but without clinical or pathological manifestation of
      Wilson's disease (WD). Genetic testing revealed a compound heterozygous ATP7B
      mutation already described in WD, p.Met645Arg (C1934TG/c.51+4A->T).
      Hypoceruloplasminaemia was detected but no clinical manifestations (hepatic or
      central nervous system) of WD were present. The authors conclude that patients
      can carry a heterozygous mutation of the ATP7B gene that is associated with
      hypoceruloplasminaemia and display no overt clinical hepatic and/or central
      nervous system manifestations of WD.

PMID- 23962631
TI  - Endoscopic burr hole evacuation of an acute subdural hematoma.
AB  - Acute subdural hematoma evacuations frequently necessitate large craniotomies
      with extended operative times and high relative blood loss, which can lead to
      additional morbidity for the patient. While endoscopic minimally invasive
      approaches to chronic subdural collections have been successfully demonstrated,
      this technique has not previously been applied to acute subdural hematomas. The
      authors report their experience with an 87-year-old patient presenting with a
      large acute right-sided subdural hematoma successfully evacuated via an
      endoscopic minimally invasive technique. The operative approach is outlined, and
      the literature on endoscopic subdural collection evacuation reviewed. 

PMID- 23962632
TI  - Vagal stimulation by manual carotid sinus massage to acutely suppress seizures.
AB  - Carotid sinus massage, a technique involving digital pressure on the richly
      innervated carotid sinus, is a time-honoured method for termination of
      supraventricular tachycardia due to paroxysmal atrial tachycardia. Vagal nerve
      stimulation, a more recent technique, employs pacemaker stimulation of the vagus
      as a treatment for refractory epilepsy. This case report discusses the use of
      carotid sinus massage to abort seizure activity. The patient used manual
      manipulation of the carotid sinus (similar to cardiology techniques) to suppress
      seizures, achieving a therapeutic neurological outcome. 

PMID- 23962633
TI  - Lymphoplasmacytic hypophysitis associated with immunoglobulin G4.
AB  - We present the unusual case of a 33-year-old woman who presented with a 2 year
      history of amenorrhoea and an expanding sellar lesion. Initial MRI revealed a
      lesion in the pituitary fossa, thought to be a pituitary adenoma. One year later,
      the lesion had enlarged by 5mm, with associated enhancement of the dura of the
      planum sphenoidale and pituitary stalk. Histopathology revealed a lymphocytic and
      plasma cell inflammatory infiltrate suggestive of lymphoplasmacytic hypophysitis
      associated with immunoglobulin G4.

PMID- 23962634
TI  - Campylobacteriosis in returning travellers and potential secondary transmission
      of exotic strains.
AB  - SUMMARY: Multilocus sequence types (STs) were determined for 232 and 737
      Campylobacter jejuni/coli isolates from Dutch travellers and domestically
      acquired cases, respectively. Putative risk factors for travel-related
      campylobacteriosis, and for domestically acquired campylobacteriosis caused by
      exotic STs (putatively carried by returning travellers), were investigated.
      Travelling to Asia, Africa, Latin America and the Caribbean, and Southern Europe
      significantly increased the risk of acquiring campylobacteriosis compared to
      travelling within Western Europe. Besides eating chicken, using antacids, and
      having chronic enteropathies, we identified eating vegetable salad outside
      Europe, drinking bottled water in high-risk destinations, and handling/eating
      undercooked pork as possible risk factors for travel-related campylobacteriosis.
      Factors associated with domestically acquired campylobacteriosis caused by exotic
      STs involved predominantly person-to-person contacts around popular holiday
      periods. We concluded that putative determinants of travel-related
      campylobacteriosis differ from those of domestically acquired infections and that
      returning travellers may carry several exotic strains that might subsequently
      spread to domestic populations even through limited person-to-person
      transmission.

PMID- 23962635
TI  - Diagnostic delay of autism in Jordan: review of 84 cases.

PMID- 23962636
TI  - Where midwives are not yet recognised: a feasibility study of professional
      midwives in Nepal.
AB  - BACKGROUND AND OBJECTIVE: the professional midwife is a key person for promoting
      maternal and family health. Not all countries have yet reached the professional
      standard for midwives set by the International Confederation of Midwives (ICM)
      and Nepal is one of these countries. This study explores the feasibility to
      establish a professional midwifery cadre in Nepal that meets the global standards
      of competencies, and to define a strategy to reach this. METHOD: a mixed-methods
      study comprised (1) policy-review (2) interviews and (3) observations. An
      assessment tool was designed for data collection and analysis using variables
      from three sources: ICM's Global Standards, the skilled birth attendant programme
      in Nepal, and JHPIEGO's site assessment tool for maternal health and new-born
      programmes. Data were collected in a desk review of education and policy
      documents, interviews with stakeholders, and site assessment of five higher
      education institutions and their hospital-based maternity departments. The
      analysis resulted in a recommended strategy. FINDINGS: six levels of education of
      nurse staff providing midwifery care were identified; all regulated under the
      Nepal Nursing Council. No legislation was in place authorising midwifery as an
      autonomous profession. A post-basic midwifery programme on first cycle-bachelor
      level was under development. A well-organised midwifery association was
      established consisting of nurses providing maternal health care. Four university
      colleges offering higher education for nurses and clinicians had a capability to
      run a midwifery programme and the fifth had a genuine interest in starting a
      midwifery programme at bachelor level. The proposed strategy includes four
      strategic objectives and interventions in relation to four components identified
      by UNFPA: Legislation and regulation; Training and education; Deployment and
      utilisation; and Professional associations. CONCLUSION AND IMPLICATION FOR
      PRACTICE: the study has delivered a proposed strategy for the Government of Nepal
      for effective management of the midwifery workforce in order to enhance midwives'
      contribution in maternity care and thus promoting improved maternal and new-born
      health. The developed analytical framework could be used as an assessment tool
      also in other countries to establish professional midwifery cadres that meets the
      global standards of competencies.

PMID- 23962637
TI  - Prevention of striae gravidarum and quality of life among pregnant Japanese
      women.
AB  - BACKGROUND: striae gravidarum affects the quality of life (QOL) of Japanese
      pregnant women. Many pregnant women use skin moisturisers to prevent striae
      gravidarum. However, the relationship between these preventive steps and QOL
      remains unclear. OBJECTIVE: to evaluate the moisturising effect and QOL of
      pregnant women in an urban prefecture in central Japan with preventive steps
      against striae gravidarum. DESIGN AND METHOD: cross-sectional study. Pregnant
      women at 36 weeks of gestation were recruited at antenatal examinations. SETTING:
      four private clinics in an urban prefecture in central Japan. PARTICIPANTS: 156
      pregnant women consisting of 83 primiparae and 73 multiparae were analysed.
      MEASUREMENTS: a self-administered questionnaire, the severity of striae
      gravidarum assessed by Davey's score and the dermatology-specific QOL were
      assessed by Skindex29. The water content in the stratum corneum of each woman's
      abdomen was measured with a Moisture checker. The Ethical Committee of Osaka
      University Medical School approved the study. FINDINGS: the prevalence of striae
      gravidarum was 37.8% and 121 (77.6%), including 76 (91.6%) primiparae and 45
      (61.6%) multiparae, said they used a cream and/or lotion in an attempt to prevent
      striae gravidarum. The water content in the stratum corneum of the abdominal wall
      increased significantly after using cream and/or lotion (p=0.001). The severity
      and presence of striae gravidarum were not correlated with the preventive steps
      or water content in the stratum corneum of the abdominal wall (p=0.330 and
      p=0.835). Pregnant women who took the preventive steps showed higher scores for
      emotion on Skindex29 than those who did not (p=0.002). Although pregnant women
      with striae gravidarum showed a lower QOL for emotion than those without striae
      gravidarum (p=0.045), those who took the preventive steps maintained a similar
      level of QOL for emotion regardless of striae gravidarum. There have been few
      trials evaluating the QOL of pregnant women with striae gravidarum so a
      comparison of results among studies and determination of an appropriate sample
      size could not be conducted. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      preventive steps increase the amount of water content in the stratum corneum but
      this does not prevent striae gravidarum. Although pregnant women with striae
      gravidarum showed a lower QOL for emotion, the preventive steps were correlated
      with the level of QOL for emotion in pregnant women with striae gravidarum.
      Midwives need to absorb such information and recommend moisturising skin care for
      pregnant women.

PMID- 23962638
TI  - Breast-feeding intention, initiation and duration among Hong Kong Chinese women:
      a prospective longitudinal study.
AB  - OBJECTIVES: to (1) estimate the breast-feeding intention, initiation and duration
      rate; (2) identify the reasons to initiate and wean breast feeding and (3)
      explore predictors of breast-feeding duration. DESIGN: a prospective longitudinal
      study SETTING: antenatal clinics of five regional hospitals from four clusters in
      Hong Kong PARTICIPANTS: a population-based sample of 2098 women in the second
      trimester of pregnancy was recruited with a systematic sampling method.
      MEASUREMENTS: three different sets of self-administered questionnaires were used
      to measure the breast-feeding intention, initiation and duration, demographic,
      socio-economic, obstetric, complications of pregnancy and intrapartum variables
      at three time points. Reasons for initiating and weaning breast feeding, the
      formal and informal supportive resources of participants during breast feeding
      were collated at the third time points. FINDINGS: the rates of artificial feeding
      and breast feeding were 41.1% and 58.9%, whereas breast-feeding intention and
      initiation rates were 85.3% and 67.0%, respectively. The breast-feeding duration
      rates were 11.1%, 10.3%, 10.7% and 26.7%, for the 'within <1 week', '1-3 weeks',
      '>3-6 weeks' and '>6 weeks' groups. The common reasons for initiating breast
      feeding were that breast feeding is beneficial for both the baby (89.8%) and
      mother (39.7%). Reasons for weaning breast feeding were insufficient breast milk
      (32.7%), tiredness and fatigue (39.7%) and return to work (29.6%). Partner,
      relatives and nurse midwives were important supportive resource during breast
      feeding. Ordinal logistic regression analysis identified five predictive factors
      of breast-feeding duration. Participants who were working part-time or were
      housewives (p=0.037), had monthly family income of <HK$10,000 (p=0.034), more
      than one child (p=0.001), positive breast-feeding intention (p=0.001) and early
      breast feeding within the first hour (p<0.0001) were more likely to have longer
      breast feeding than their counterparts. CONCLUSION: mothers in Hong Kong do not
      meet the recommendation of the international standards for breast feeding.
      Understanding of reasons for initiation, weaning and predictors of breast-feeding
      duration can help nurse midwives to develop and customise effective strategies to
      promote and encourage breast feeding. IMPLICATIONS FOR PRACTICE: the findings are
      important for a process-oriented breast-feeding training programme for nurse
      midwives. New strategies should be implemented for prolonging breast-feeding
      duration among perinatal women.

PMID- 23962639
TI  - The challenges facing midwifery educators in sustaining a future education
      workforce.
AB  - BACKGROUND: national and international trends have identified concerns over the
      ability of health and social care workforces in meeting the needs of service
      users. Attention has increasingly been drawn to problems of recruiting and
      retaining professionals within higher education; however data in relation to the
      midwifery profession is scant. AIM: to examine the perceptions and experiences of
      midwifery educators, in south-west England, about the challenges facing them
      sustaining the education workforce of the future. DESIGN: a mixed methodology
      approach was adopted involving heads of midwifery education and midwife
      educators. METHODOLOGY: midwifery participants were recruited from three higher
      education institutions in south west England. Data collection comprised of self
      administered questionnaires plus individual qualitative interviews with heads of
      midwifery education (n=3), and tape recorded focus groups with midwife academics
      (n=19). Numerical data were analysed using descriptive statistics. Textual data
      were analysed for themes that represented the experiences and perspectives of
      participants. Ethics approval was granted by one University Ethics committee.
      FINDINGS: demographic data suggests that within south-west England, there is a
      clear ageing population and few in possession of a doctorate within midwifery.
      The six identified sub-themes represented in the data describe challenges and
      tensions that midwifery academics experienced in their efforts to attract new
      recruits and retain those in post in a highly changing educational environment
      which demands more from a contracting workforce. CONCLUSION AND IMPLICATIONS FOR
      PRACTICE: there remain some serious challenges facing midwifery educators in
      sustaining the future education workforce, which if unresolved may jeopardise
      standards of education and quality of care women receive. Active succession
      planning and more radical approaches that embrace flexible careers will enable
      educational workforce to be sustained and by a clinically credible and scholarly
      orientated midwifery workforce.

PMID- 23962640
TI  - Responding to a crying infant - you do not learn it overnight: a phenomenological
      study.
AB  - OBJECTIVE: to examine the views and practices of first-time and experienced
      mothers in response to infant crying during the first 12 weeks post birth.
      DESIGN: longitudinal, qualitative study using an interpretive, phenomenological
      approach. SETTING: postnatal hospital and home settings in Switzerland.
      PARTICIPANTS: maximum variation sampling of 15 new mothers of diverse parity and
      educational background who had given birth to a full-term healthy neonate.
      METHODS: participant observations in the postnatal ward and two narrative
      interviews at participants' homes at 6-8 and 12-14 weeks post partum. Data
      analysis used interpretive approaches of case analysis, thematic analysis and
      exemplars. FINDINGS: first-time mothers showed some soothing skills from the
      beginning, but fine-tuned their practices of handling the crying infant and
      managing their own reactions. With growing experience mothers acquired a
      differentiated understanding of the crying's reason and urgency and used more
      successful soothing techniques. At the same time they learned to assess and
      mitigate their own stress reactions by self-soothing and adopting realistic
      expectations of normal infant behaviour. Experienced mothers knew the infant's
      frequent crying would diminish after a while whereas first-time mothers coped
      without this positive expectation. KEY CONCLUSIONS: with increasing child-care
      experience mothers' skills and attitudes towards crying changed, leading to a
      calmer and less escalating response to their crying infant. IMPLICATIONS FOR
      PRACTICE: inexperienced mothers need information on neonatal crying behaviour and
      on parents' stress response. They should be taught how to recognise and respond
      to the new-born's signals, and how to cope with their own stress. Postnatal care
      should provide novice mothers to learn from experienced role models.

PMID- 23962641
TI  - [Feasibility of patient-injected anticoagulation therapy: the GRANTED
      experience].
AB  - BACKGROUND: Injectable anticoagulation therapy is indicated for several months
      following diagnosis of venous thromboembolic disease (VTE) in a context of active
      neoplasia. Certain studies have shown an improvement in patient compliance using
      self-injections. PURPOSE: Allow patients to safely make their own injections of
      anticoagulants after checking their aptitude and motivation. METHODS: At the
      prescribing physician's request, the GRANTED network provided patients and/or the
      resource person with specific education and training. The educational program was
      proposed to patients with an indication for a treatment for at least 3 months.
      After becoming familiar with the injection material and its manipulation, the
      patient and/or resource person performed sham injections on test materials.
      Patients were then allowed to decide for themselves whether or not to participate
      in the self-injection protocol. The prescribing physician received a report from
      the training team. RESULTS: From November 2010 to July 2012, 39 patients
      participated in the educational program, generally in a context of vitamin K
      antagonist prescriptions. Sixteen of these patients had a neoplasia. The
      educational program corrected erroneous or imprecise points of information,
      particularly concerning syringe purging. DISCUSSION: The education program proved
      to be interesting for points other than those initially foreseen and allowed the
      team to rectify a certain number of erroneous messages unrecognized by the
      prescribing physicians. This result goes in line with the need for accompanying
      patients who have a prescription for self-injections and also emphasizes the need
      for careful follow-up.

PMID- 23962642
TI  - A systematic review of self-help for disfigurement: effectiveness, usability, and
      acceptability.
AB  - Self-help has been found to be efficacious in treating mood disorders, however,
      little is known about its use, effectiveness, or user satisfaction, in reducing
      distress associated with disfigurement. This review describes the content and
      focus of self-help interventions available in this area. A systematic search and
      appraisal protocol facilitated identification of studies, extraction of data, and
      appraisal of quality. Clinical trials were included if the primary method of
      intervention delivery was via self-help. Other types of study were included if
      they investigated user perspectives of a self-help intervention. Eleven studies
      covering a range of populations met the inclusion criteria. There is tentative
      support for the use of self-help to manage anxiety associated with disfigurement
      but little is known about the management of other psychosocial difficulties.
      Further research and intervention development is required to examine the
      effectiveness, acceptability, and utility of self-help in managing the appearance
      related distress associated with disfigurement. 

PMID- 23962643
TI  - Chronic exercise downregulates myocardial myoglobin and attenuates nitrite
      reductase capacity during ischemia-reperfusion.
AB  - The infarct sparing effects of exercise are evident following both long-term and
      short-term training regimens. Here we compared the infarct-lowering effects of
      nitrite therapy, voluntary exercise, and the combination of both following
      myocardial ischemia-reperfusion (MI/R) injury. We also compared the degree to
      which each strategy increased cardiac nitrite levels, as well as the effects of
      each strategy on the nitrite reductase activity of the heart. Mice subjected to
      voluntary wheel running (VE) for 4weeks displayed an 18% reduction in infarct
      size when compared to sedentary mice, whereas mice administered nitrite therapy
      (25mg/L in drinking water) showed a 53% decrease. However, the combination of VE
      and nitrite exhibited no further protection than VE alone. Although the VE and
      nitrite therapy mice showed similar nitrite levels in the heart, cardiac nitrite
      reductase activity was significantly reduced in the VE mice. Additionally, the
      cardiac protein expression of myoglobin, a known nitrite reductase, was also
      reduced after VE. Further studies revealed that cardiac NFAT activity was lower
      after VE due to a decrease in calcineurin activity and an increase in GSK3beta
      activity. These data suggest that VE downregulates cardiac myoglobin levels by
      inhibiting calcineurin/NFAT signaling. Additionally, these results suggest that
      the modest infarct sparing effects of VE are the result of a decrease in the
      hearts ability to reduce nitrite to nitric oxide during MI/R. 

PMID- 23962645
TI  - Covalent attachment of Mn-porphyrin onto doxorubicin-loaded poly(lactic acid)
      nanoparticles for potential magnetic resonance imaging and pH-sensitive drug
      delivery.
AB  - In this paper, theranostic nanoparticles (MnP-DOX NPs) were fabricated by
      conjugating Mn-porphyrin onto the surface of doxorubicin (DOX)-loaded poly(lactic
      acid) (PLA) nanoparticles (DOX NPs) for potential T1 magnetic resonance imaging
      and pH-sensitive drug delivery. An in vitro drug release study showed that the
      release rate of DOX from MnP-DOX NPs was slow at neutral pH but accelerated
      significantly in acidic conditions. It was found that MnP-DOX NPs could be easily
      internalized by HeLa cells and effectively suppressed the growth of HeLa cells
      and HT-29 cells due to the accelerated drug release in acidic lysosomal
      compartments. Magnetic resonance imaging (MRI) scanning analysis demonstrated
      that MnP-DOX NPs had much higher longitudinal relaxivity in water (r1 value of
      27.8 mM(-1) s(-1) of Mn(3+)) than Mn-porphyrin (Mn(III)TPPS3NH2; r1 value of 6.70
      mM(-1) s(-1) of Mn(3+)), behaving as an excellent contrast agent for T1-weighted
      MRI both in vitro and in vivo. In summary, such a smart and promising
      nanoplatform integrates multiple capabilities for effective cancer diagnosis and
      therapy.

PMID- 23962646
TI  - Iron staining in gammopathy-related crystal-storing histiocytosis: a misleading
      feature to the differential diagnosis with Gaucher's disease.

PMID- 23962644
TI  - Structure-function-property-design interplay in biopolymers: spider silk.
AB  - Spider silks have been a focus of research for almost two decades due to their
      outstanding mechanical and biophysical properties. Recent advances in genetic
      engineering have led to the synthesis of recombinant spider silks, thus helping
      to unravel a fundamental understanding of structure-function-property
      relationships. The relationships between molecular composition, secondary
      structures and mechanical properties found in different types of spider silks are
      described, along with a discussion of artificial spinning of these proteins and
      their bioapplications, including the role of silks in biomineralization and
      fabrication of biomaterials with controlled properties. 

PMID- 23962647
TI  - A diagonal landing task to assess dynamic postural stability in ACL reconstructed
      females.
AB  - BACKGROUND: Previous research has used time to stabilization (TTS) from forward
      landing tasks to assess dynamic postural stability in ACL reconstructed (ACLR)
      athletes in order to identify impaired sensorimotor control and mechanical
      stability. This may not be an appropriate test due to the fact that research has
      suggested that ACL injury has a multi-planar mechanism of injury. The purpose of
      the present study was to compare TTS values from a forward land and a diagonal
      land to determine if diagonal landing TTS values are more sensitive to dynamic
      postural stability deficits in female ACLR athletes. METHODS: A group of ACL
      reconstructed female athletes and a group of female control athletes performed
      three forward lands and three diagonal lands onto a force-plate and remained
      still on one foot for 15s. TTS was calculated for the anterior-posterior and
      medial-lateral ground reaction forces as well as the resultant vector of both
      forces. RESULTS: All three TTS values were significantly increased in the ACLR
      group from the control group for the diagonal landing task. There was no
      difference in TTS values between the groups for the forward landing task.
      CONCLUSION: TTS values from a diagonal landing are more sensitive at detecting
      impaired dynamic postural stability in a group of female ACLR athletes compared
      to TTS values from a forward land. LEVEL OF EVIDENCE: III - Casecontrolled study.

PMID- 23962648
TI  - Ventral tegmental ionotropic glutamate receptor stimulation of nucleus accumbens
      tonic dopamine efflux blunts hindbrain-evoked phasic neurotransmission:
      implications for dopamine dysregulation disorders.
AB  - Activation of glutamate receptors within the ventral tegmental area (VTA)
      stimulates extrasynaptic (basal) dopamine release in terminal regions, including
      the nucleus accumbens (NAc). Hindbrain inputs from the laterodorsal tegmental
      nucleus (LDT) are critical for elicitation of phasic VTA dopamine cell activity
      and consequent transient dopamine release. This study investigated the role of
      VTA ionotropic glutamate receptor (iGluR) stimulation on both basal and LDT
      electrical stimulation-evoked dopamine efflux in the NAc using in vivo
      chronoamperometry and fixed potential amperometry in combination with stearate
      graphite paste and carbon fiber electrodes, respectively. Intra-VTA infusion of
      the iGluR agonists (+/-)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic
      acid (AMPA; 1 MUg/MUl) or N-methyl-d-aspartic acid (NMDA; 2 MUg/MUl) enhanced
      basal NAc dopamine efflux. This iGluR-mediated potentiation of basal dopamine
      efflux was paralleled by an attenuation of LDT-evoked transient NAc dopamine
      efflux, suggesting that excitation of basal activity effectively inhibited the
      capacity of hindbrain afferents to elicit transient dopamine efflux. In line with
      this, post-NMDA infusion of the dopamine D2 autoreceptor (D2R) agonist quinpirole
      (1 MUg/MUl; intra-VTA) partially recovered NMDA-mediated attenuation of LDT
      evoked NAc dopamine, while concurrently attenuating NMDA-mediated potentiation of
      basal dopamine efflux. Post-NMDA infusion of quinpirole (1 MUg/MUl) alone
      attenuated basal and LDT-evoked dopamine efflux. Taken together, these data
      reveal that hyperstimulation of basal dopamine transmission can stunt hindbrain
      burst-like stimulation-evoked dopamine efflux. Inhibitory autoreceptor mechanisms
      within the VTA help to partially recover the magnitude of phasic dopamine efflux,
      highlighting the importance of both iGluRs and D2 autoreceptors in maintaining
      the functional balance of tonic and phasic dopamine neurotransmission.
      Dysregulation of this balance may have important implications for disorders of
      dopamine dysregulation such as attention deficit hyperactivity disorder.

PMID- 23962649
TI  - Alpha2 GABAA receptor sub-units in the ventral hippocampus and alpha5 GABAA
      receptor sub-units in the dorsal hippocampus mediate anxiety and fear memory.
AB  - Temporary neuronal inactivation of the ventral hippocampus with the GABAA agonist
      muscimol suppresses unconditioned fear behavior (anxiety) but inactivation of the
      dorsal hippocampus does not. On the other hand, inactivating the dorsal
      hippocampus disrupts fear memory, while inactivating the ventral hippocampus does
      not. Here we investigate the roles of hippocampal GABAA receptor sub-units in
      mediating these anxiolytic and amnesic effects of GABAA receptor agonists. We
      microinfused TPA023 (alpha2 agonist) or TB-21007 (inverse alpha5 agonist) into
      the dorsal or ventral hippocampus prior to testing rats in two animal models of
      anxiety: the elevated plus-maze and shock-probe burying test. Twenty-four hours
      later rats were re-tested in the shock-probe chamber with a non-electrified probe
      to assess their memory of the initial shock-probe experience (i.e., fear memory).
      We found that TPA023 was anxiolytic in the plus-maze and shock-probe burying
      tests when microinfused into the ventral hippocampus. However, TPA023 did not
      affect anxiety-related behavior when infused into the dorsal hippocampus.
      Conversely, we found that the alpha5 sub-unit inverse agonist TB-21007 impaired
      rats' memory of the initial shock-probe experience when infused into the dorsal
      hippocampus, but not when infused into the ventral hippocampus. This double
      dissociation suggests that alpha2 GABAA receptor sub-units in the ventral
      hippocampus mediate unconditioned fear or anxiety, while alpha5 GABAA receptor
      sub-units in the dorsal hippocampus mediate conditioned fear memory. 

PMID- 23962650
TI  - Development and validation of a complete GATE model of the Siemens Inveon
      trimodal imaging platform.
AB  - This article presents and validates a newly developed GATE model of the Siemens
      Inveon trimodal imaging platform. Fully incorporating the positron emission
      tomography (PET), single-photon emission computed tomography (SPECT), and
      computed tomography (CT) data acquisition subsystems, this model enables
      feasibility studies of new imaging applications, the development of
      reconstruction and correction algorithms, and the creation of a baseline against
      which experimental results for real data can be compared. Model validation was
      based on comparing simulation results against both empirical and published data.
      The PET modality was validated using the NEMA NU-4 standard. Validations of SPECT
      and CT modalities were based on assessment of model accuracy compared to
      published and empirical data on the platform. Validation results show good
      agreement between simulation and empirical data of approximately +/- 5%.

PMID- 23962651
TI  - Internet addiction and psychopathology in a community before and during an
      economic crisis.
AB  - Background. Internet addiction disorder (IAD) is a novel concept under scrutiny
      for a definite inclusion in the psychiatric taxonomy, after showing correlations
      with overt expressions of psychopathology. This study aims to assist the
      scientific dialogue concerning IAD while presenting comparative data on
      adolescent psychopathology before and during a major economic crisis that has
      affected Greece from 2010 onwards. Methods. This is a cross-sectional study of a
      high school student population, aged 12-18, on IAD which follows-up a 2006
      survey, and is carried out 5 years later at the same school classes. A comparison
      on psychopathological symptoms between the two samples is carried out to confirm
      any underlying correlations with IAD while providing some first insight on any
      effects of the economic crisis on adolescent psyche. Results. Results indicate
      that Internet addiction is increased in this population paralleling the increase
      in Internet availability at home. Adolescents affected with IAD present with more
      psychopathological symptoms. A comparison between the 2006 and 2011 samples
      reveals lower rates of general psychopathology but similar burden of reported
      symptoms. Conclusions. Those findings are discussed in the framework of
      adolescent coping to adversity, individual reactions to major crises, as well as
      the general debate regarding the value of IAD as a distinct diagnosis. The
      effects of the economic crisis may have triggered an adaptive response in the
      adolescent population although IAD as a distinct nosological entity is clearly
      linked to more symptoms of overt psychopathology. Directions are offered for
      further research in countries affected by crises. 

PMID- 23962652
TI  - Glaucoma diagnostic ability of ganglion cell-inner plexiform layer thickness
      differs according to the location of visual field loss.
AB  - OBJECTIVE: To determine whether the ganglion cell-inner plexiform layer (GCIPL)
      or circumpapillary retinal nerve fiber layer (cpRNFL) is better at distinguishing
      eyes with early glaucoma from normal eyes on the basis of the the initial
      location of the visual field (VF) damage. DESIGN: Retrospective, observational
      study. PARTICIPANTS: Eighty-four patients with early glaucoma and 43 normal
      subjects were enrolled. The patients with glaucoma were subdivided into 2 groups
      according to the location of VF damage: (1) an isolated parafoveal scotoma (PFS,
      N = 42) within 12 points of a central 10 degrees in 1 hemifield or (2) an
      isolated peripheral nasal step (PNS, N = 42) within the nasal periphery outside
      10 degrees of fixation in 1 hemifield. METHODS: All patients underwent macular
      and optic disc scanning using Cirrus high-definition optical coherence tomography
      (Carl Zeiss Meditec, Dublin, CA). The GCIPL and cpRNFL thicknesses were compared
      between groups. Areas under the receiver operating characteristic curves (AUCs)
      were calculated. MAIN OUTCOME MEASURES: Comparison of diagnostic ability using
      AUCs. RESULTS: The average and minimum GCIPL of the PFS group were significantly
      thinner than those of the PNS group, whereas there was no significant difference
      in the average retinal nerve fiber layer (RNFL) thickness between the 2 groups.
      The AUCs of the average (0.962) and minimum GCIPL (0.973) thicknesses did not
      differ from that of the average RNFL thickness (0.972) for discriminating
      glaucomatous changes between normal and all glaucoma eyes (P =0.566 and 0.974,
      respectively). In the PFS group, the AUCs of the average (0.988) and minimum
      GCIPL (0.999) thicknesses were greater than that of the average RNFL thickness
      (0.961, P =0.307 and 0.125, respectively). However, the AUCs of the average
      (0.936) and minimum GCIPL (0.947) thicknesses were lower than that of the average
      RNFL thickness (0.984) in the PNS group (P =0.032 and 0.069, respectively).
      CONCLUSIONS: The GCIPL parameters were more valuable than the cpRNFL parameters
      for detecting glaucoma in eyes with parafoveal VF loss, and the cpRNFL parameters
      were better than the GCIPL parameters for detecting glaucoma in eyes with
      peripheral VF loss. Clinicians should know that the diagnostic capability of
      macular GCIPL parameters depends largely on the location of the VF loss.

PMID- 23962654
TI  - Linking minds and brains.
AB  - When I first came across William James' dictum that " ... this sense of sameness
      is the very keel and backbone of our thinking," I thought he had foreseen the
      importance of cross-correlation in the brain, and told myself to find out how he
      had reached this conclusion. When I finally did this a year or two ago, I slowly
      came to realize that I had completely misunderstood him; from the full quote it
      is absolutely clear that his dictum cannot be referring to the process by which a
      cortical simple cell responds selectively to the orientation of features in a
      visual image, as I had originally supposed. If one translates the original dictum
      into two more prosaic modern versions, his version would say: "Our minds could
      not think at all without neural circuits in our brains that compute auto
      correlations," but in my mistaken interpretation the last word would be "cross
      correlations." Others may have made the same mistake, but the difference is
      profound, and finding what he really meant has been a revelation to me. This
      essay explains the revelation, describes how to determine experimentally whether
      the brain does auto- or cross-correlation, and gives the result of preliminary
      experiments showing clearly that it does both. A revised view of the visual
      cortex as autocorrelator as well as cross-correlator claims to tell us what
      complex cells in the visual cortex do, and it assigns a role to its columnar
      structure that is as important to fulfilling that role as the concept of the
      receptive field has been to understanding the simple cells' fulfillment of
      theirs. The new view has compelling features, broad implications, and suggests a
      plausible model of how neural circuits in the cortex achieve thought, but it
      needs further testing. 

PMID- 23962653
TI  - Neutrophil collagenase, gelatinase, and myeloperoxidase in tears of patients with
      stevens-johnson syndrome and ocular cicatricial pemphigoid.
AB  - OBJECTIVE: To investigate the levels of matrix metalloproteinases (MMPs),
      myeloperoxidase (MPO), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in
      tears of patients with Stevens-Johnson syndrome (SJS) and ocular cicatricial
      pemphigoid (OCP). DESIGN: Prospective, noninterventional cohort study.
      PARTICIPANTS: Four SJS patients (7 eyes), 19 OCP patients (37 eyes), and 20
      healthy controls who underwent phacoemulsification (40 eyes). METHODS: Tear
      washes were collected from all patients and were analyzed for levels of MMP-2,
      MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 using multianalyte bead-based
      enzyme-linked immunosorbent assays. Total MMP activity was determined using a
      fluorometric assay. Correlation studies were performed between the various
      analytes within study groups. MAIN OUTCOME MEASURES: Levels of MMP-2, MMP-3, MMP
      7, MMP-8, MMP-9, MMP-12, MPO, and TIMP-1 (in nanograms per microgram of protein)
      and total MMP activity (in relative fluorescent units per minute per microgram of
      protein) in tears; MMP-8-to-TIMP-1 ratio; MMP-9-to-TIMP-1 ratio; and the
      correlations between MMP-8 and MMP-9 and both MMP and MPO. RESULTS: MMP-8, MMP-9,
      and MPO levels were elevated significantly in SJS and OCP tears (SJS>OCP) when
      compared with controls. The MMP activity was highest in SJS patients, whereas OCP
      patients and controls showed lower and similar activities. The TIMP-1 levels were
      decreased in SJS and OCP patients when compared with those in controls, with
      levels in OCP patients reaching significance. The MMP-8-to-TIMP-1 and MMP-9-to
      TIMP-1 ratios were markedly elevated in SJS and OCP tears (SJS>OCP) when compared
      with those of controls. Across all study groups, MMP-9 levels correlated strongly
      with MMP-8 and MPO levels, and MMP-8 correlated with MPO, but it did not reach
      significance in SJS patients. There was no relationship between MMP-7 and MPO.
      CONCLUSIONS: Because MMP-8 and MPO are produced by inflammatory cells,
      particularly neutrophils, the correlation data indicate that they may be the
      common source of elevated enzymes, including MMP-9, in SJS and OCP tears.
      Elevated MMP-to-TIMP ratios and MMP activity suggest an imbalance in tear MMP
      regulation that may explain the predisposition of these patients to demonstrate
      corneal melting and chronic complications associated with persistent
      inflammation. Myeloperoxidase in tears may be a sensitive and specific marker for
      the quantification of ocular inflammation.

PMID- 23962655
TI  - Leg preference associated with protective stepping responses in older adults.
AB  - BACKGROUND: Asymmetries in dynamic balance stability have been previously
      observed. The goal of this study was to determine whether leg preference
      influenced the stepping response to a waist-pull perturbation in older adult
      fallers and non-fallers. METHODS: 39 healthy, community-dwelling, older adult
      (>65 years) volunteers participated. Participants were grouped into non-faller
      and faller cohorts based on fall history in the 12 months prior to the study.
      Participants received 60 lateral waist-pull perturbations of varying magnitude
      towards their preferred and non-preferred sides during quiet standing. Outcome
      measures included balance tolerance limit, number of recovery steps taken and
      type of recovery step taken for perturbations to each side. FINDINGS: No
      significant differences in balance tolerance limit (P >= 0.102) or number of
      recovery steps taken (eta(2)partial <= 0.027; P >= 0.442) were observed between
      perturbations towards the preferred and non-preferred legs. However, non-faller
      participants more frequently responded with a medial step when pulled towards
      their non-preferred side and cross-over steps when pulled towards their preferred
      side (P=0.015). INTERPRETATION: Leg preference may influence the protective
      stepping response to standing balance perturbations in older adults at risk for
      falls, particularly with the type of recovery responses used. Such asymmetries in
      balance stability recovery may represent a contributing factor for falls among
      older individuals and should be considered for rehabilitation interventions aimed
      at improving balance stability and reducing fall risk.

PMID- 23962657
TI  - Outcomes of polypoidal choroidal vasculopathy treated with ranibizumab
      monotherapy.

PMID- 23962658
TI  - Persistent outer retinal fluid following non-posturing surgery for idiopathic
      macular hole.
AB  - AIM: To present the anatomical and visual outcomes of patients with hypo
      reflective cystic defects in outer fovea (outer foveal defect; OFD) in macular
      holes repaired with non-posturing vitrectomy and short term gas tamponade. To
      identify the incidence and risk factors for developing OFD foveal defect. METHOD:
      A prospective consecutive case series of 58 patients undergoing macular hole
      surgery was undertaken. OFD detected on 2-week postoperative Optical coherence
      tomography (OCT) was measured. In these patients OCT was performed monthly until
      resolution of OCT. RESULTS: 27 eyes (46.6%) had an outer defect at 2 weeks, the
      presence of which was significantly associated with macular holes with larger
      base diameters preoperatively (p=0.006). All defects closed spontaneously without
      further intervention, and the final vision was not affected by the presence of an
      OFD. Visual recovery was only slightly (and not significantly) delayed by the
      presence of an outer defect. CONCLUSIONS: This is the first study of outcomes of
      OFDs following macular hole surgery in patients who did not posture
      postoperatively. OFDs are common but do not adversely affect visual outcomes.

PMID- 23962656
TI  - Towards precision medicine: advances in computational approaches for the analysis
      of human variants.
AB  - Variations and similarities in our individual genomes are part of our history,
      our heritage, and our identity. Some human genomic variants are associated with
      common traits such as hair and eye color, while others are associated with
      susceptibility to disease or response to drug treatment. Identifying the human
      variations producing clinically relevant phenotypic changes is critical for
      providing accurate and personalized diagnosis, prognosis, and treatment for
      diseases. Furthermore, a better understanding of the molecular underpinning of
      disease can lead to development of new drug targets for precision medicine.
      Several resources have been designed for collecting and storing human genomic
      variations in highly structured, easily accessible databases. Unfortunately, a
      vast amount of information about these genetic variants and their functional and
      phenotypic associations is currently buried in the literature, only accessible by
      manual curation or sophisticated text text-mining technology to extract the
      relevant information. In addition, the low cost of sequencing technologies
      coupled with increasing computational power has enabled the development of
      numerous computational methodologies to predict the pathogenicity of human
      variants. This review provides a detailed comparison of current human variant
      resources, including HGMD, OMIM, ClinVar, and UniProt/Swiss-Prot, followed by an
      overview of the computational methods and techniques used to leverage the
      available data to predict novel deleterious variants. We expect these resources
      and tools to become the foundation for understanding the molecular details of
      genomic variants leading to disease, which in turn will enable the promise of
      precision medicine.

PMID- 23962660
TI  - Discovery of novel 4-anilinoquinazoline derivatives as potent inhibitors of
      epidermal growth factor receptor with antitumor activity.
AB  - Two new series of new compounds containing a 6-amino-substituted group or 6
      acrylamide-substituted group linked to a 4-anilinoquinazoline nucleus have been
      discovered as potential EGFR inhibitors. These compounds proved efficient effects
      on antiproliferative activity and EGFR-TK inhibitory activity. Especially, N(6)
      ((5-bromothiophen-2-yl)methyl)-N(4)-(3-chlorophenyl)quinazoline-4,6-diamine (5e),
      showed the most potent inhibitory activity (IC50=3.11MUM for Hep G2, IC50=0.82MUM
      for A549). The EGFR molecular docking model suggested that the new compound is
      nicely bound to the region of EGFR, and cell morphology by Hoechst stain
      experiment suggested that these compounds efficiently induced apoptosis of A549
      cells. 

PMID- 23962659
TI  - Dietary fish oil and DHA down-regulate antigen-activated CD4+ T-cells while
      promoting the formation of liquid-ordered mesodomains.
AB  - We have demonstrated previously that n-3 PUFA endogenously produced by fat-1
      transgenic mice regulate CD4+ T-cell function by affecting the formation of lipid
      rafts, liquid-ordered mesodomains in the plasma membrane. In the present study,
      we tested the effects of dietary sources of n-3 PUFA, i.e. fish oil (FO) or
      purified DHA, when compared with an n-6 PUFA-enriched maize oil control diet in
      DO11.10 T-cell receptor transgenic mice. Dietary n-3 PUFA were enriched in CD4+ T
      cells, resulting in the increase of the n-3:n-6 ratio. Following antigen-specific
      CD4+ T-cell activation by B-lymphoma cells pulsed with the ovalbumin 323-339
      peptide, the formation of liquid-ordered mesodomains at the immunological synapse
      relative to the whole CD4+ T-cell, as assessed by Laurdan labelling, was
      increased (P< 0.05) in the FO-fed group. The FO diet also suppressed (P< 0.05)
      the co-localisation of PKCtheta with ganglioside GM1
      (monosialotetrahexosylganglioside), a marker for lipid rafts, which is consistent
      with previous observations. In contrast, the DHA diet down-regulated (P< 0.05)
      PKCtheta signalling by moderately affecting the membrane liquid order at the
      immunological synapse, suggesting the potential contribution of the other major n
      3 PUFA components of FO, including EPA. 

PMID- 23962661
TI  - Predicting cycling accident risk in Brussels: a spatial case-control approach.
AB  - This paper aims at predicting cycling accident risk for an entire network and
      identifying how road infrastructure influences cycling safety in the Brussels
      Capital Region (Belgium). A spatial Bayesian modelling approach is proposed using
      a binary dependent variable (accident, no accident at location i) constructed
      from a case-control strategy. Control sites are sampled along the 'bikeable' road
      network in function of the potential bicycle traffic transiting in each ward.
      Risk factors are limited to infrastructure, traffic and environmental
      characteristics. Results suggest that a high risk is statistically associated
      with the presence of on-road tram tracks, bridges without cycling facility,
      complex intersections, proximity to shopping centres or garages, and busy van and
      truck traffic. Cycle facilities built at intersections and parked vehicles
      located next to separated cycle facilities are also associated with an increased
      risk, whereas contraflow cycling is associated with a reduced risk. The cycling
      accident risk is far from being negligible in points where there is actually no
      reported cycling accident but where they are yet expected to occur. Hence,
      mapping predicted accident risks provides planners and policy makers with a
      useful tool for accurately locating places with a high potential risk even before
      accidents actually happen. This also provides comprehensible information for
      orienting cyclists to the safest routes in Brussels. 

PMID- 23962662
TI  - Single-port laparoscopic total mesorectal excision with transanal resection
      (transabdominal transanal resection) for low rectal cancer: initial experience
      with 22 cases.
AB  - BACKGROUND: Total mesorectal excisions (TME) with transanal resection and
      coloanal anastomosis (CAA) represent one of the standard surgical treatments for
      low rectal cancers. We report our initial experiences with trans-abdominal trans
      anal resections (TATAR) with TME, performed using a single-port laparoscopic
      surgeries (SPLS) approach for low rectal cancers. METHODS: Between June 2009 and
      April 2011, 22 low rectal cancer patients underwent SPLS TATAR with TME. SPLS was
      performed transumbilically or through predetermined stoma sites. Conventional
      laparoscopic instruments were used, and the intracorporeal procedures and range
      of operation did not differ. After a full laparoscopic TME to the pelvic floor
      muscles, the specimen was pulled through the anus. CAA was completed with
      transanal hand sewn sutures. Patient and tumor characteristics and operative,
      pathologic, and postoperative outcomes were studied. RESULTS: SPLS TATAR with TME
      was successful in all patients. No additional incisions for trocars or
      conversions to open surgery were performed. The median incision length, operative
      time, and postoperative length of stay were 2.0 cm (range: 1.5-2.5), 260 min
      (range: 190-380), and 6 days (range: 4-16), respectively. The median number of
      harvested lymph nodes was 22 (range: 9-42). The median distal margin from the
      tumor was 2.0 cm (range: 0.3-4.0). No intraoperative complications were noted.
      CONCLUSIONS: SPLS TATAR with TME was safe and feasible. In addition to cosmetic
      advantages, oncologic requirements for specimens, including adequate margins and
      sufficient lymph node harvesting could be fulfilled entirely. However, the
      technique and oncologic safety warrant further evaluation and prospective
      randomized studies.

PMID- 23962663
TI  - Practical implications of postoperative adhesions for preoperative consent and
      operative technique.
AB  - Adhesions complicate most intra-peritoneal operations. Once adhesions have
      formed, patients are at life-long risk for complications that include small bowel
      obstruction, increased risks during subsequent operations and female infertility.
      This has two implications for the daily work of surgeons. On the one hand,
      surgeons need to include the risks from adhesions during pre-operative consent.
      On the other hand, surgeons need to use operative techniques that minimize
      adhesions. Therefore this review focuses on the practical implications of
      adhesions for preoperative consent and operative technique. 

PMID- 23962666
TI  - [Towards a better understanding of patients].

PMID- 23962664
TI  - Comparison of EJC-enhanced and EJC-independent NMD in human cells reveals two
      partially redundant degradation pathways.
AB  - Nonsense-mediated mRNA decay (NMD) is a eukaryotic post-transcriptional gene
      regulation mechanism that eliminates mRNAs with the termination codon (TC)
      located in an unfavorable environment for efficient translation termination. The
      best-studied NMD-targeted mRNAs contain premature termination codons (PTCs);
      however, NMD regulates even many physiological mRNAs. An exon-junction complex
      (EJC) located downstream from a TC acts as an NMD-enhancing signal, but is not
      generally required for NMD. Here, we compared these "EJC-enhanced" and "EJC
      independent" modes of NMD with regard to their requirement for seven known NMD
      factors in human cells using two well-characterized NMD reporter genes
      (immunoglobulin MU and beta-Globin) with or without an intron downstream from the
      PTC. We show that both NMD modes depend on UPF1 and SMG1, but detected transcript
      specific differences with respect to the requirement for UPF2 and UPF3b,
      consistent with previously reported UPF2- and UPF3-independent branches of NMD.
      In addition and contrary to expectation, a higher sensitivity of EJC-independent
      NMD to reduced UPF2 and UPF3b concentrations was observed. Our data further
      revealed a redundancy of the endo- and exonucleolytic mRNA degradation pathways
      in both modes of NMD. Moreover, the relative contributions of both decay pathways
      differed between the reporters, with PTC-containing immunoglobulin MU transcripts
      being preferentially subjected to SMG6-mediated endonucleolytic cleavage, whereas
      beta-Globin transcripts were predominantly degraded by the SMG5/SMG7-dependent
      pathway. Overall, the surprising heterogeneity observed with only two NMD
      reporter pairs suggests the existence of several mechanistically distinct
      branches of NMD in human cells. 

PMID- 23962665
TI  - Mutational analysis of the yeast RNA helicase Sub2p reveals conserved domains
      required for growth, mRNA export, and genomic stability.
AB  - Sub2p/UAP56 is a highly conserved DEAD-box RNA helicase involved in the packaging
      and nuclear export of mRNA/protein particles (mRNPs). In Saccharomyces
      cerevisiae, Sub2p is recruited to active chromatin by the pentameric THO complex
      and incorporated into the larger transcription-export (TREX) complex. Sub2p also
      plays a role in the maintenance of genome integrity as its inactivation causes
      severe transcription-dependent recombination of DNA. Despite the central role of
      Sub2p in early mRNP biology, little is known about its function. Here, we report
      the presence of an N-terminal motif (NTM) conserved specifically in the Sub2p
      branch of RNA helicases. Mutation of the NTM causes nuclear accumulation of
      poly(A)(+) RNA and impaired growth without affecting core helicase functions.
      Thus, the NTM functions as an autonomous unit. Moreover, two sub2 mutants, that
      are deficient in ATP binding, act in a trans-dominant negative fashion for growth
      and induce high recombination rates in vivo. Although wild-type Sub2p is
      prevented access to transcribed loci in such a background, this does not
      mechanistically explain the phenotype. 

PMID- 23962667
TI  - The effect of exercise interventions on cognitive outcome in Alzheimer's disease:
      a systematic review.
AB  - BACKGROUND: Non-pharmacological interventions may have a role in both the
      prevention and slowing down of disease progression in Alzheimer's disease (AD).
      The role of exercise in disease prevention, for example, has been extensively
      evaluated in large epidemiological studies. Much less is known about the
      potential benefit of exercise in patients already diagnosed with AD. It was
      therefore the aim of this systematic review to assess the effectiveness of
      exercise in attenuating cognitive decline within AD. METHOD: A systematic review
      was conducted statistically accompanied by a meta-analysis. Publications between
      January 1991 and October 2012 were identified by searching the electronic
      databases PubMed, Science Direct, Web of Knowledge, and PsychINFO. Selected
      studies required AD patients to take part in an exercise-based randomized
      controlled trial (RCT) and have a cognitive outcome measure. RESULTS: Six RCTs
      were identified that exclusively considered the effect of exercise in AD
      patients. Exercise generally had a positive effect on rate of cognitive decline
      in AD. A meta-analysis found that exercise interventions have a positive effect
      on global cognitive function, 0.75 (95% CI = 0.32-1.17). CONCLUSIONS: From the
      six studies reviewed, the evidence suggests that exercise can have a positive
      effect on rate of cognitive decline in AD. However, the variation between study
      designs makes conclusions regarding the optimum intervention on cognitive outcome
      in AD difficult. Well-designed and powered RCTs are still needed to ascertain the
      efficacy of exercise in slowing down cognitive impairment in AD patients.
      However, a positive initial indication for exercise efficacy justifies such
      efforts.

PMID- 23962668
TI  - Systematic review and meta-analysis of psychiatric disorder and the perpetration
      of partner violence.
AB  - Backgrounds. The extent to which psychiatric disorders are associated with an
      increased risk of violence to partners is unclear. This review aimed to establish
      risk of violence against partners among men and women with diagnosed psychiatric
      disorders. Methods. Systematic review and meta-analysis. Searches of eleven
      electronic databases were supplemented by hand searching, reference screening and
      citation tracking of included articles, and expert recommendations. Results.
      Seventeen studies were included, reporting on 72 585 participants, but only three
      reported on past year violence. Pooled risk estimates could not be calculated for
      past year violence against a partner and the three studies did not consistently
      report increased risk for any diagnosis. Pooled estimates showed an increased
      risk of having ever been physically violent towards a partner among men with
      depression (odds ratio (OR) 2.8, 95% confidence intervals (CI) 2.5-3.3),
      generalized anxiety disorder (GAD) (OR 3.2, 95% CI 2.3-4.4) and panic disorder
      (OR 2.5, 95% CI C% 1.7-3.6). Increased risk was also found among women with
      depression (OR 2.4, 95% CI 2.1-2.8), GAD (OR 2.4, 95% CI 1.9-3.0) and panic
      disorder (OR 1.9, 95% CI 1.4-2.5). Conclusions. Psychiatric disorders are
      associated with high prevalence and increased odds of having ever been physically
      violent against a partner. As history of violence is a predictor of current
      violence, mental health professionals should ask about previous partner violence
      when assessing risk. 

PMID- 23962669
TI  - Separation of time-based and trial-based accounts of the partial reinforcement
      extinction effect.
AB  - Two appetitive conditioning experiments with rats examined time-based and trial
      based accounts of the partial reinforcement extinction effect (PREE). In the
      PREE, the loss of responding that occurs in extinction is slower when the
      conditioned stimulus (CS) has been paired with a reinforcer on some of its
      presentations (partially reinforced) instead of every presentation (continuously
      reinforced). According to a time-based or "time-accumulation" view (e.g.,
      Gallistel and Gibbon, 2000), the PREE occurs because the organism has learned in
      partial reinforcement to expect the reinforcer after a larger amount of time has
      accumulated in the CS over trials. In contrast, according to a trial-based view
      (e.g., Capaldi, 1967), the PREE occurs because the organism has learned in
      partial reinforcement to expect the reinforcer after a larger number of CS
      presentations. Experiment 1 used a procedure that equated partially and
      continuously reinforced groups on their expected times to reinforcement during
      conditioning. A PREE was still observed. Experiment 2 then used an extinction
      procedure that allowed time in the CS and the number of trials to accumulate
      differentially through extinction. The PREE was still evident when responding was
      examined as a function of expected time units to the reinforcer, but was
      eliminated when responding was examined as a function of expected trial units to
      the reinforcer. There was no evidence that the animal responded according to the
      ratio of time accumulated during the CS in extinction over the time in the CS
      expected before the reinforcer. The results thus favor a trial-based account over
      a time-based account of extinction and the PREE. This article is part of a
      Special Issue entitled: Associative and Temporal Learning. 

PMID- 23962671
TI  - The impact of domestication on fearfulness: a comparison of tonic immobility
      reactions in wild and domesticated finches.
AB  - We examined differences in the fear response between Bengalese finches and their
      wild ancestor, the white-backed munia, to explore the evolutionary mechanisms of
      behavioural changes due to domestication. The Bengalese finch (Lonchura striata
      var. domestica) was domesticated from the wild-living white-backed munia (L.
      striata) approximately 250 years ago. A previous study indicated that Bengalese
      finches sing much more complex songs than white-backed munias. We hypothesised
      that Bengalese finches are likely able to allocate more resources to reproduction
      in exchange for reduced survival effort. We measured tonic immobility (TI)
      reactions as a response to physical restraint to evaluate fearfulness related to
      coping with predation. The results showed that Bengalese finches exhibited
      decreased TI responses compared with white-backed munias. TI responses were
      unaffected by sex, body weight or growth conditions. These differences suggest
      that the fearfulness in Bengalese finches has been reduced by selective pressure
      during domestication. Bengalese finches may have been able to increase the
      investment of energy in reproduction in exchange for reduced costs of predation
      and coping necessary to survive in the wild; these behavioural changes may have
      been a major target of domestication effects in this species. 

PMID- 23962670
TI  - Interactions of timing and prediction error learning.
AB  - Timing and prediction error learning have historically been treated as
      independent processes, but growing evidence has indicated that they are not
      orthogonal. Timing emerges at the earliest time point when conditioned responses
      are observed, and temporal variables modulate prediction error learning in both
      simple conditioning and cue competition paradigms. In addition, prediction
      errors, through changes in reward magnitude or value alter timing of behavior.
      Thus, there appears to be a bi-directional interaction between timing and
      prediction error learning. Modern theories have attempted to integrate the two
      processes with mixed success. A neurocomputational approach to theory development
      is espoused, which draws on neurobiological evidence to guide and constrain
      computational model development. Heuristics for future model development are
      presented with the goal of sparking new approaches to theory development in the
      timing and prediction error fields. 

PMID- 23962672
TI  - Adaptation of timing behavior to a regular change in criterion.
AB  - This study examined how operant behavior adapted to an abrupt but regular change
      in the timing of reinforcement. Pigeons were trained on a fixed interval (FI) 15
      s schedule of reinforcement during half of each experimental session, and on an
      FI 45-s (Experiment 1), FI 60-s (Experiment 2), or extinction schedule
      (Experiment 3) during the other half. FI performance was well characterized by a
      mixture of two gamma-shaped distributions of responses. When a longer FI schedule
      was in effect in the first half of the session (Experiment 1), a constant
      interference by the shorter FI was observed. When a shorter FI schedule was in
      effect in the first half of the session (Experiments 1, 2, and 3), the transition
      between schedules involved a decline in responding and a progressive rightward
      shift in the mode of the response distribution initially centered around the
      short FI. These findings are discussed in terms of the constraints they impose to
      quantitative models of timing, and in relation to the implications for
      information-based models of associative learning. This article is part of a
      Special Issue entitled: Associative and Temporal Learning. 

PMID- 23962673
TI  - The effects of process-focused versus experience-focused narratives in a breast
      cancer treatment decision task.
AB  - OBJECTIVE: To examine the effect of patient narratives that discuss decision
      processes versus patient experiences on decisions about treatments for early
      stage breast cancer. METHODS: We recruited 300 women with no previous history of
      breast cancer to imagine that they had been diagnosed with early stage breast
      cancer and to choose between mastectomy and lumpectomy with radiation. Before
      learning about their treatment options, participants were randomly assigned to
      one of four conditions with videotaped stories from fictitious cancer survivors,
      using a 2 (content: experience versus process) * 2 (emotional valence: positive
      only vs. positive and negative) factorial design, or a control condition with no
      stories. We measured information search, treatment intentions, and decision
      satisfaction. RESULTS: Participants viewing process narratives spent more time
      searching for information. Participants viewing experience narratives reported a
      greater ability to imagine what it was like to experience the treatments; they
      also evaluated their decision more positively on several dimensions. CONCLUSIONS:
      Process narratives appeared to guide information search, and experience
      narratives improved evaluations of the decision process. PRACTICE IMPLICATIONS:
      There is no evidence that process and experience narratives 'bias' decisions in
      the same manner as outcome narratives. Further, their potential to focus patient
      attention on key information and increase patient confidence in decision making
      appears significant.

PMID- 23962674
TI  - Genetic marker of norepinephrine synthesis predicts individual differences in
      post-error slowing: a pilot study.
AB  - When our brain detects the commission of an error, we slow down immediately
      thereafter: a phenomenon called post-error slowing (PES). Some researchers have
      speculated that slowing after unexpected errors or negative feedback is related
      to the activity of the neuromodulatory locus coeruleus-norepinephrine system. In
      the present pilot study, we tested whether individual differences in the size of
      PES are related to differences in genetic predisposition related to
      norepinephrine synthesis. In a sample of 100 healthy adults, we studied the
      dependency of an individual's size of PES on the DBH5'-ins/del polymorphism-a
      variation in the DBH gene associated with the production of the enzyme dopamine
      beta-hydroxylase, which catalyzes the conversion of dopamine to norepinephrine.
      DBH5'-ins/del heterozygotes, who have intermediate levels of plasma DbetaH
      activity, showed increased PES in a Simon task compared to del/del homozygotes
      and ins/ins homozygotes, who have low and high levels of plasma DbetaH activity,
      respectively. This outcome pattern presents preliminary evidence that the size of
      PES varies with DbetaH activity and, presumably, NE release according to an
      inverted U-shape: intermediate levels of DbetaH activity and NE release are
      associated with larger post-error adjustments. 

PMID- 23962675
TI  - Self-referential processing is distinct from semantic elaboration: evidence from
      long-term memory effects in a patient with amnesia and semantic impairments.
AB  - We report data demonstrating that self-referential encoding facilitates memory
      performance in the absence of effects of semantic elaboration in a severely
      amnesic patient also suffering semantic problems. In Part 1, the patient, GA, was
      trained to associate items with the self or a familiar other during the encoding
      phase of a memory task (self-ownership decisions in Experiment 1 and self
      evaluation decisions in Experiment 2). Tests of memory showed a consistent self
      reference advantage, relative to a condition where the reference was another
      person in both experiments. The pattern of the self-reference advantage was
      similar to that in healthy controls. In Part 2 we demonstrate that GA showed
      minimal effects of semantic elaboration on memory for items he semantically
      classified, compared with items subject to physical size decisions; in contrast,
      healthy controls demonstrated enhanced memory performance after semantic relative
      to physical encoding. The results indicate that self-referential encoding, not
      semantic elaboration, improves memory in amnesia. Self-referential processing may
      provide a unique scaffold to help improve learning in amnesic cases. 

PMID- 23962676
TI  - Vessel size imaging (VSI) by robust magnetic resonance (MR) relaxometry: MR-VSI
      of solid tumors in correlation with immunohistology and intravital microscopy.
AB  - The aim of this study was to evaluate a robust magnetic resonance (MR) vessel
      size imaging (VSI) method for the noninvasive assessment of mean vessel size in
      solid tumors in a clinical dose range of ultrasmall superparamagnetic particles
      of iron oxide (USPIO). Therefore, USPIO-enhanced MR-VSI was performed on DU-4475,
      MDA-MB-435, and EOMA tumor-bearing mice xenografts with known differences in
      angiogenic activity and vessel morphology. MR results were compared to vessel
      sizes determined by immunohistochemistry (anti-CD31) and by intravital microscopy
      (IVM). MR-VSI revealed significantly different mean vessel sizes between the
      xenograft models at both USPIO doses (DU-4475: 20.6 +/- 4.9 MUm; MDA-MB-435: 37.4
      +/- 8.8 MUm; and EOMA: 60.3 +/-9.6 MUm at 80 MUmol/kg; p < .05).
      Immunohistochemistry revealed lower values for all tumor entities, whereas the
      size distribution was in line with MR-measurements. IVM corroborated the MR
      results for DU-4475 and MDA-MB435, but showed similar vessel sizes for MDA-MB-435
      and EOMA. Our MR-VSI method allowed a noninvasive estimation of the mean vessel
      size in mice xenograft solid tumors with variable vascularity using a clinically
      relevant USPIO dose range.

PMID- 23962677
TI  - Behavioural and physiological responses of Gammarus fossarum (Crustacea
      Amphipoda) exposed to silver.
AB  - The study aims at investigating the effects of silver (Ag), a re-emerging
      contaminant, on physiological and behavioural responses in Gammarus fossarum. In
      a first experiment, G. fossarum Ag LC50s were evaluated during 96 h under semi
      static mode of exposure. Juveniles appeared to be more sensitive to Ag (LC5096h:
      1.01 MUg L(-1)) than ovigerous females (LC5096h: 1.9 MUg L(-1)) and adult males
      (LC5096h: 2.2 MUg L(-1)). In a second experiment, the physiological (osmo
      /ionoregulation; antioxidant enzymes; lipid peroxidation (LPO)) and behavioural
      (locomotor activity and ventilation) responses of male G. fossarum exposed to Ag
      (0, 0.5, 1, 2, and 4 MUg L(-1)) were investigated. The mortality and Ag
      bioconcentration of gammarids exposed to Ag were significantly higher than
      controls. Concerning physiological responses, a 48 h-exposure to Ag had no impact
      on catalase activity but led to a significant decrease of haemolymph osmolality
      and [Na(+)]. On the contrary, LPO, Se-GPx and Na(+)/K(+)-ATPase activity were
      significantly increased. Behavioural responses, such as locomotor and ventilatory
      activities, were also significantly reduced in Ag exposed gammarids. After 96 h
      exposure, especially to 0.5 MUg Ag L(-1), most responses (ventilation, locomotor
      activity, haemolymph osmolality and [Na(+)]) were even more pronounced and
      haemolymph [Cl(-)] was significantly decreased but, contrary to observations
      after 48 h-exposure, Na(+)/K(+)-ATPase activity was significantly reduced. Our
      results demonstrate the drastic effects of realistic [Ag] concentration (0.5 MUg
      Ag L(-1)) on an ubiquitous and functionally important freshwater invertebrate
      (implied in detritus breakdown), but also strongly suggest an energetic
      reallocation to the detriment of locomotor activity and in favour of maintenance
      functions (i.e., osmoregulation and detoxification). These results highlight the
      risk represented by Ag and the need to perform integrated studies (at different
      scales, from individual to ecosystem).

PMID- 23962678
TI  - Compartmental flux and in situ methods underestimate total feed nitrogen as
      judged by the omasal sampling method due to ignoring soluble feed nitrogen flow.
AB  - The objective of the present study was to estimate ruminal feed N outflow in
      lactating cows using the omasal sampling, compartmental flux or in situ method. A
      total of five ruminally fistulated Finnish Ayrshire dairy cows were used in a 5 *
      5 Latin square study with 21 d periods. Experimental silages of grass or red
      clover harvested at two stages of maturity in addition to a supplement of 9.0 kg
      concentrate/d were fed to the cows. In vivo omasal N flow was determined using
      the omasal sampling technique. Ruminal in situ N flow was calculated from N
      intake and degradability (38 MUm nylon bags). The samples of ruminal contents and
      faeces were divided into seven particle-size fractions by wet sieving; the
      concentrations of indigestible neutral-detergent fibre and N were used to
      calculate N flow in the compartmental flux method. In vivo omasal N flow was
      greater for the red clover silage diets than for the grass silage diets. The N
      flow calculated using the compartmental flux technique and that calculated using
      the in situ technique were highly correlated, but both were less than and poorly
      correlated with the in vivo N flow. In both in situ and compartmental flux
      techniques, forage maturity increased the particle-associated N flow, with the
      increase being significantly greater for the red clover diets than for the grass
      silage diets. In conclusion, the compartmental flux and in situ methods described
      the N flow associated with the particle fractions rather than the total ruminal
      outflow of feed N.

PMID- 23962679
TI  - Psychiatric patient stratification using biosignatures based on cerebrospinal
      fluid protein expression clusters.
AB  - Psychiatric disorders are caused by perturbed molecular pathways that affect
      brain circuitries. The identification of specific biosignatures that are the
      result of altered pathway activities in major depression, bipolar disorder and
      schizophrenia can contribute to a better understanding of disease etiology and
      aid in the implementation of diagnostic assays. In the present study we
      identified disease-specific protein biosignatures in cerebrospinal fluid of
      depressed (n: 36), bipolar (n: 27) and schizophrenic (n: 35) patients using the
      Reverse Phase Protein Microarray technology. These biosignatures were able to
      stratify patient groups in an objective manner according to cerebrospinal fluid
      protein expression patterns. Correct classification rates were over 90%. At the
      same time several protein sets that play a role in neuronal growth, proliferation
      and differentiation (NEGR1, NPDC1), neurotransmission (SEZ6) and protection from
      oxidative damage (GPX3) were able to distinguish diseased from healthy
      individuals (n: 35) indicating a molecular signature overlap for the different
      psychiatric phenotypes. Our study is a first step toward implementing a
      psychiatric patient stratification system based on molecular biosignatures.
      Protein signatures may eventually be of use as specific and sensitive biomarkers
      in clinical trials not only for patient diagnostic and subgroup stratification
      but also to follow treatment response. 

PMID- 23962680
TI  - [Embryo vitrification: French clinical practice analysis for BLEFCO].
AB  - Frozen thawed embryo transfer is currently an important part of present-day
      assisted reproductive technology (ART) aiming at increasing the clinical
      pregnancy rate per oocyte retrieval. Although slow freezing method has been the
      reference during 2 decades, the recent years witnessed an expansion of ultrarapid
      cryopreservation method named vitrification. Recently in France, vitrification
      has been authorized for cryopreserving human embryos. Therefore BLEFCO consortium
      decides to perform a descriptive study through questionnaires to evaluate the
      state of vitrification in the French clinical practice. Questionnaires were
      addressed to the 105 French centres of reproductive biology and 60 were fully
      completed. Data analysis revealed that embryo survival rate as well as, clinical
      pregnancy rate were increased after vitrification technology when compared to
      slow freezing procedure. Overall, these preliminary data suggest that
      vitrification may improve ART outcomes through an increasing of the cumulative
      pregnancy rate per oocyte retrieval. 

PMID- 23962681
TI  - An animal model of stress-induced cardiomyopathy utilizing the social defeat
      paradigm.
AB  - Stress-induced cardiomyopathy (SIC) is a form of acute heart disease triggered by
      extreme psychological stress. In patients who develop SIC, the outward symptoms
      are almost indistinguishable from acute myocardial infarction (AMI). However,
      some important criteria differentiate patients with SIC from those with AMI.
      Patients with SIC: (1) experience some form of extreme psychological stress from
      minutes to hours before developing heart disease, (2) do not suffer from
      atherosclerosis or coronary artery obstruction, and 3) exhibit abnormal
      ballooning of the left ventricle. In the present study, the resident-intruder
      (RI) social defeat test was investigated as a potential rat model for stressed
      induced cardiomyopathy. Adult Long-Evans rats were implanted with a biotelemetry
      transmitter for ECG recordings and habituated for two weeks. An intruder rat was
      placed in the cage of a resident rat behind a wire-mesh partition for 5 min. The
      partition was then removed for 5 min to allow direct contact between the intruder
      and resident rats. After this interval, the wire-mesh partition was replaced and
      the intruder rat remained behind the partition for an additional 50 min.
      Behavioral responses were noted and ECG recordings were collected during the
      entire 60-min testing period. Upon completion of the test, the intruder rat was
      removed from the cage of the resident rat and sacrificed. The heart was examined
      and blood was collected. Heart weight/body weight ratio, left ventricle/body
      weight ratio, heart length, plasma corticosterone levels, and plasma troponin I
      levels of intruder rats were significantly higher as compared to control rats.
      Intruder rats significantly increased their heart rate during the first 5 min of
      the RI test. It is concluded that the RI test to induce social defeat is a novel
      rodent paradigm for modeling stress-induced cardiomyopathy in the human.

PMID- 23962682
TI  - Multilayers based on cationic nanocomplexes for co-delivery of doxorubicin and
      DNA.
AB  - Co-delivery of drugs and genes has synergistic advantages in many fields such as
      cancer treatments. In this study, we present a multilayers for co-delivery of
      doxorubicin (DOX) and DNA. Ferrocene-modified polyethyleneimine (PEI-Fc) is
      synthesized, and it can form micelles in solution with ferrocene core and PEI
      shell. DOX and DNA are thus incorporated into the core and shell of the micelles,
      respectively, to form the PEI-Fc-DOX-DNA nanocomplexes. Such cationic
      nanocomplexes are used to construct multilayers through layer-by-layer assembly
      with negatively charged dextran sulfate (DS). We show that the multilayers can
      release DOX, and the release can be significantly enhanced in a hydrogen peroxide
      condition. Moreover, the multilayers have the ability to transfect cells through
      a substrate-mediated mode. The (PEI-Fc-DOX-DNA/DS) multilayers can be potentially
      applied to the biomedical devices for cancer treatment, regenerative medicine,
      etc. 

PMID- 23962683
TI  - Hybrid technique for ventricular septal defect closure in a dog using an
      Amplatzer(r) Duct Occluder II.
AB  - A left-to-right shunting muscular ventricular septal defect (VSD) was diagnosed
      in a 4-month-old, female, 1.8 kg Bichon Frise - poodle mix dog. Echocardiographic
      evidence of cardiac remodeling, calculated pulmonary blood flow (Qp) to systemic
      blood flow (Qs) ratio of 2.8, and radiographic evidence of pulmonary edema
      supported the diagnosis of a hemodynamically important VSD. Using a combination
      of surgery and interventional catheter-based techniques to approach the VSD
      through the right ventricle, the VSD was occluded with an Amplatzer((r)) Duct
      Occluder (ADO) II device. The ADO II is a low profile, flexible device originally
      developed for patent ductus arteriosus closure in humans that has been used to
      close muscular and perimembranous VSD in children. This report describes the
      hybrid procedure and imaging that was essential for successful occlusion of the
      VSD in this dog.

PMID- 23962684
TI  - Permanent junctional reciprocating tachycardia in a dog.
AB  - A 5-year-old male English Bulldog was presented with a 1-year history of
      paroxysmal supraventricular tachycardia (SVT) partially responsive to amiodarone.
      At admission the surface ECG showed sustained runs of a narrow QRS complex
      tachycardia, with a ventricular cycle length (R-R interval) of 260 ms,
      alternating with periods of sinus rhythm. Endocardial mapping identified the
      electrogenic mechanism of the SVT as a circus movement tachycardia with
      retrograde and decremental conduction along a concealed postero-septal
      atrioventricular pathway (AP) and anterograde conduction along the
      atrioventricular node. These characteristics were indicative of a permanent
      junctional reciprocating tachycardia (PJRT). Radiofrequency catheter ablation of
      the AP successfully terminated the PJRT, with no recurrence of tachycardia on
      Holter monitoring at 12 months follow-up.

PMID- 23962685
TI  - Carotid endarterectomy for symptomatic low-grade carotid stenosis.
AB  - OBJECTIVE: Although the management of carotid disease is well established for
      symptomatic lesions >= 70%, the surgical treatment for a symptomatic <= 50%
      stenosis is not supported by data from randomized trials. Factors other than
      lumen narrowing, such as plaque instability, seem to be involved in cerebral and
      retinal ischemic events. This study analyzes the early-term and long-term
      outcomes of carotid endarterectomy (CEA) performed in patients with low-grade (<=
      50% on North American Symptomatic Carotid Endarterectomy Trial criteria)
      symptomatic carotid stenosis. METHODS: The study involves 57 consecutive patients
      undergoing CEA for symptomatic low-grade carotid disease at our institution over
      5 years, and 21 (36.8%) had experienced more than one ischemic event. Overall, 48
      (84.2%) had a minor stroke, and nine (15.8%) had an episode of retinal ischemia.
      Diagnosis was made by a vascular neurologist based on an ultrasound examination
      combined with noninvasive imaging studies, after ruling out other possible causes
      of embolization. Before CEA, all patients were receiving antiplatelet treatment,
      and 87% were taking statins. All patients underwent eversion CEA under general
      deep anesthesia, with selective shunting. All carotid plaques were examined
      histologically. Long-term follow-up (median, 28 months; mean, 32 +/- 5 months;
      range, 3-56 months) was obtained for 55 patients. RESULTS: No 30-day strokes or
      deaths occurred, and no patients had recurrent neurologic events related to the
      revascularized hemisphere during the follow-up. No late carotid occlusions were
      detected, but one asymptomatic moderate restenosis was documented. There were
      seven late deaths (12.7%), none of which were stroke-related. Survival rates were
      98% at 1 year and 90% at 3 years. All removed carotid plaques showed different
      features of ulceration or rupture, with underlying hemorrhage associated with a
      thrombus. CONCLUSIONS: This study shows that CEA is a safe, effective, and
      durable treatment for patients with symptomatic low-grade carotid stenosis
      associated with unstable plaque. Patients had excellent protection against
      further ischemic events and survived long enough to justify the initial surgical
      risk. Plaque instability seems to play a major part in the onset of ischemic
      events, regardless the entity of lumen narrowing.

PMID- 23962686
TI  - Antigen recovery and preservation using the microwave irradiation of biological
      samples for transmission electron microscopy analysis.
AB  - Most studies using microwave irradiation (MWI) for the preparation of tissue
      samples have reported an improvement in structural integrity. However, there have
      been few studies on the effect of microwave (MW) on antigen preservation during
      sample preparation prior to immunolocalization. This report documents our
      experience of specimen preparation using an automatic microwave apparatus to
      obtain antigen preservation and retrieval. We tested the effects of MW processing
      vs. conventional procedures on the morphology and antigenicity of two different
      tissues: the brain and mammary gland, whose chemical composition and anatomical
      organization are quite different. We chose to locate the transcription factor
      PPARbeta/delta using immunocytochemistry on brain tissue sections from hamsters.
      Antigen retrieval protocols involving MWI were used to restore immunoreactivity.
      We also studied the efficiency of the ultrastructural immunolocalization of both
      PPARgamma and caveolin-1 following MWI vs. conventional treatment, on mammary
      gland tissue from mice at 10 days of lactation. Our findings showed that the
      treatment of tissue samples with MWI, in the context of a process lasting just a
      few hours from fixation to immunolocalization, enabled similar, or even better,
      results than conventional protocols. The quantification of immunolabeling for cav
      1 indicated an increase in density of up to three-fold in tissues processed in
      the microwave oven. Furthermore, MW treatment permitted the localization of
      PPARbeta/delta in glutaraldehyde-fixed specimens, which was impossible in the
      absence of MWI. This study thus showed that techniques involving the use of
      microwaves could largely improve both ultrastructure and immunodetection. 

PMID- 23962687
TI  - Plastid trnF pseudogenes are present in Jaltomata, the sister genus of Solanum
      (Solanaceae): molecular evolution of tandemly repeated structural mutations.
AB  - Extensive gene duplication arranged in a tandem array is rare in the plastome of
      embryophytes. Interestingly, we found pseudogene copies of the trnF gene in the
      genus Jaltomata, the sister genus of Solanum where such gene duplication has been
      previously reported. In each Jaltomata sequence available we found two pseudogene
      copies in close 5'-proximity to the original functional gene. The size of each
      pseudogene copy ranged between 17 and 48 bp and the anticodon domain was
      identified as the most conserved element. A common ATT(G)n motif is particularly
      interesting and its modifications were found to border the 3' of the duplicated
      regions. Other motifs were partial residues, or entire parts of the T- and D
      domains, and both domains proved to be variable in length among the pseudogenes
      identified. The residues of the 3' and 5' acceptor stem were not found among the
      copies. We further compared the newly discovered copies of Jaltomata with those
      ones previously described from Solanum and inferred phylogenetic relationships of
      the copies aligned. The evolution of Solanum copies, in contrast to Jaltomata, is
      hard to explain as resulting only in parsimonious changes since reticulate
      evolutionary patterns were detected among the copies. The dynamic evolutionary
      patterns of Solanum might be explained by possible inter- or intrachromosomal
      recombination.

PMID- 23962688
TI  - Novel alternative splice variants of chicken NPAS3 are expressed in the
      developing central nervous system.
AB  - We report isolation of novel splice variants of chicken Neuronal Per-Arnt-Sim
      domain protein 3 (cNPAS3) gene distinct from the previously predicted cNPAS3 at
      the 5' end. Newly identified cNPAS3 splice variants feature N-terminus coding
      sequences with high degrees of homology to human NPAS3 (hNAPS3). We also show
      that the alternative splicing pattern of NPAS3 is conserved between chicken and
      human. RNA in situ hybridization indicated that the expression of cNPAS3 in the
      developing central nervous system (CNS) is limited to the ventricular zone and
      only partially overlaps with that of chicken Reelin (cReelin), the only known
      regulatory target gene of NPAS3 in the adult brain. Overexpression of cNPAS3 by
      in ovo electroporation had little effect on the expression of Sox2, a marker for
      neural precursors, or of Isl1/2, a marker for early differentiating motor
      neurons. Taken together with the little effect of cNPAS3 overexpression on
      cReelin, it is noted that the function of NPAS3 in the developing CNS remains to
      be determined. Still, identification of proper cDNA sequences for cNPAS3 should
      represent a solid beginning of the understanding process.

PMID- 23962690
TI  - Dementia from the ABCD1 mutation c.1415-1416delAG in a female carrier.
AB  - OBJECTIVES: Progressive dementia is a rare phenotypic feature of female X-ALD
      carriers. Even rarer is the additional presence of further risk factors for
      dementia, such as diabetes, hypothyroidism, and hepatopathy. We report a unique
      female X-ALD carrier presenting with severe, progressive dementia,
      paraspasticity, sphincteric dysfunction, and multisystem disease. CASE REPORT: A
      79 years-old female with a history of strumectomy, diabetes, hepatopathy,
      hypothyroidism, arterial hypertension, hiatal hernia, left retinal ablation,
      ovariectomy, hysterectomy, osteoporosis, bilateral hip endoprosthesis, and
      neurogenic bladder dysfunction developed slowly progressive cognitive decline
      since age of 77 years. She had been identified as a female carrier of X-ALD in
      12/2010 upon a family screening. At age of 79 years she presented with severe
      dementia, anxiety, unsteadiness, helplessness, hypertelorism, exaggerated patella
      tendon reflexes, reduced Achilles tendon reflexes, club feet, contractures of the
      ankles, the knees, and the hips, and the inability to stay or walk. Cerebral CT
      showed diffuse atrophy, demyelination periventricularly, small lacunas in the
      basal ganglia, and small calcifications of the basal ganglia and the temporal
      lobe on the right side. Differential diagnoses of dementia were considered but
      were all excluded upon the clinical presentation, blood chemical investigations,
      imaging studies, and the pattern of neuropsychological deficits. CONCLUSIONS:
      With progression of the disease manifesting X-ALD carriers may develop
      progressive severe dementia, severe paraspasticity, and sphincteric dysfunction.
      Female carriership of X-ALD can be a differential diagnosis of dementia.

PMID- 23962689
TI  - Genetic variation of the cutaneous HPA axis: an analysis of UVB-induced
      differential responses.
AB  - Mammalian skin incorporates a local equivalent of the hypothalamic-pituitary
      adrenal (HPA) axis that is critical in coordinating homeostatic responses against
      external noxious stimuli. Ultraviolet radiation B (UVB) is a skin-specific
      stressor that can activate this cutaneous HPA axis. Since C57BL/6 (B6) and DBA/2J
      (D2) strains of mice have different predispositions to sensorineural pathway
      activation, we quantified expression of HPA axis components at the gene and
      protein levels in skin incubated ex vivo after UVB or sham irradiation. Urocortin
      mRNA was up-regulated after all doses of UVB with a maximum level at 50 mJ/cm(2)
      after 12h for D2 and at 200 mJ/cm(2) after 24h for B6. Proopiomelanocortin mRNA
      was enhanced after 6h with the peak after 12h and at 200 mJ/cm(2) for both
      genotypes of mice. ACTH levels in tissue and media increased after 24h in B6 but
      not in D2. UVB stimulated beta-endorphin expression was higher in D2 than in B6.
      Melanocortin receptor 2 mRNA was stimulated by UVB in a dose-dependent manner,
      with a peak at 200 mJ/cm(2) after 12h for both strains. The expression of Cyp11a1
      mRNA - a key mitochondrial P450 enzyme in steroidogenesis, was stimulated at all
      doses of UVB irradiation, with the most pronounced effect after 12-24h. UVB
      radiation caused, independently of genotype, a dose-dependent increase in
      corticosterone production in the skin, mainly after 24h of histoculture. Thus,
      basal and UVB stimulated expression of the cutaneous HPA axis differs as a
      function of genotype: D2 responds to UVB earlier and with higher amplitude than
      B6, while B6 shows prolonged (up to 48 h) stress response to a noxious stimulus
      such as UVB.

PMID- 23962691
TI  - A conceptual framework for improving well-being in people with a diagnosis of
      psychosis.
AB  - Background. Well-being is important for people with severe mental illness, such
      as psychosis. So far, no clear concept of well-being exists for this client
      group. A recent systematic review and narrative synthesis developed a static
      framework of well-being components. The present study aims to validate the static
      framework and to illuminate the processes by which well-being is experienced by
      people with psychosis. Methods. Semi-structured interviews were conducted with 23
      service users with psychosis exploring their experience of well-being. Thematic
      analysis was used to analyse the data employing techniques taken from grounded
      theory to enhance the rigour of the analysis. Respondent validation was
      undertaken with 13 of the 23 participants. Results. Three superordinate
      categories of well-being were identified: current sense of self; transition to
      enhanced sense of self and enhanced sense of self. In the dynamic process of
      improving well-being the current sense of self undergoes a transition to an
      enhanced sense of self. The four factors influencing the transition are
      consistent with the static framework of well-being, hence validating the static
      framework. In addition, we identified three determinants of current sense of self
      and seven indicators of enhanced sense of self, which represent the achievement
      of improved well-being. Conclusions. This study provides an empirically
      defensible framework for understanding well-being in terms of determinants,
      influences and indicators. The influences are targets for interventions to
      improve well-being, and the indicators are outcome domains to assess the
      effectiveness of services in supporting well-being. 

PMID- 23962692
TI  - Account of Haly Abbas regarding the management of hydrocephalus in children: a
      text from medieval times.
AB  - OBJECTIVE: To present the text on hydrocephalus from Haly Abbas's book Kitab al
      Maliki / Liber Regius (The Royal Book), which was accepted as a classical
      textbook in the Eastern and Western worlds for a long time. METHODS: The Arabic
      (Suleymaniye Manuscript Library, Murad Molla Collection, Nr: 1482 and Bulak, 1294
      /1877) and the Latin (Venice, 1492) versions of the related chapter was
      translated and compared to create an English text. Additionally, relevant
      literature was reviewed in detail. RESULTS: The text on hydrocephalus in Haly
      Abbas's The Royal Book virtually resembles Paul of Aegina's work. For
      hydrocephalic cases where the fluid collects between skin and pericranium, and
      pericranium and bone, Haly Abbas had made little change in surgical intervention;
      for the third type, skin incision, he preferred a T-type incision instead of an H
      type. Like Paul of Aegina, Haly Abbas also did not advise any surgical
      intervention for the cases of hydrocephalus, where fluid accumulation is between
      bone and the dura mater. CONCLUSIONS: Haly Abbas's approach to hydrocephalus was
      as brave as that of his predecessors Antyllus, Oribasius, and Paulus, although
      the cases they dealt with were almost all cephalic hematomas. Although his
      chapter on the treatment of water accumulation in the head contains surgical
      interventions in extracranial hydrocephalic conditions, his account on
      hydrocephalus is extremely precise and gives adequate detail as in other chapters
      in his book.

PMID- 23962693
TI  - Neurodegenerative and psychiatric overlap in frontotemporal lobar degeneration: a
      case of familial frontotemporal dementia presenting with catatonia.
AB  - The behavioral variant of frontotemporal dementia (FTD) begins with psychiatric
      symptoms, including changes in personal conduct and/or interpersonal behavior.
      Prior to developing cognitive impairment, differentiating FTD from primary
      psychiatric disorders, like schizophrenia, can be challenging. This paper
      presents a case of traumatic brain injury with subsequent depression and
      catatonia. Initial response to electroconvulsive therapy and lorazepam suggested
      primarily psychiatric pathology. Subsequent symptom progression, reduced
      treatment response, and detailed family history evaluation led to the diagnosis
      of familial FTD with C9ORF72 mutation. This case highlights that familial FTD can
      present with depression with suicidal tendencies and catatonia, and that the
      responsiveness of these behavioral manifestations to standard therapies can
      change over time.

PMID- 23962695
TI  - Radical production inside an acoustically driven microbubble.
AB  - The chemical production of radicals inside acoustically driven bubbles is
      determined by the local temperature inside the bubbles and by their composition
      at collapse. By means of a previously validated ordinary differential equations
      (ODE) model [L. Stricker, A. Prosperetti, D. Lohse, Validation of an approximate
      model for the thermal behavior in acoustically driven bubbles, J. Acoust. Soc.
      Am. 130 (5) (2011) 3243-3251], based on boundary layer assumption for mass and
      heat transport, we study the influence of different parameters on the radical
      production. We perform different simulations by changing the driving frequency
      and pressure, the temperature of the surrounding liquid and the composition of
      the gas inside the bubbles. In agreement with the experimental conditions of new
      generation sonochemical reactors, where the bubbles undergo transient cavitation
      oscillations [D. F. Rivas, L. Stricker, A. Zijlstra, H. Gardeniers, D. Lohse, A.
      Prosperetti, Ultrasound artificially nucleated bubbles and their sonochemical
      radical production, Ultrason. Sonochem. 20 (1) (2013) 510-524], we mainly
      concentrate on the initial chemical transient and we suggest optimal working
      ranges for technological applications. The importance of the chemical composition
      at collapse is reflected in the model, including the role of entrapped water
      vapor. We in particular study the exothermal reactions taking place in H2 and O2
      mixtures. At the exact stoichiometric mixture 2:1 the highest internal bubble
      temperatures are achieved.

PMID- 23962694
TI  - Somatostatin receptor type 2-based reporter expression after plasmid-based in
      vivo gene delivery to non-small cell lung cancer.
AB  - Plasmids tend to have much lower expression than viruses. Gene expression after
      systemic administration of plasmid vectors has not been assessed using
      somatostatin receptor type 2 (SSTR2)-based reporters. The purpose of this work
      was to identify gene expression in non-small cell lung cancer (NSCLC) after
      systemic liposomal nanoparticle delivery of plasmid containing SSTR2-based
      reporter gene. In vitro, Western blotting was performed after transient
      transfection with the plasmid cytomegalovirus (CMV)-SSTR2, CMV-TUSC2-IRES-SSTR2,
      or CMV-TUSC2. SSTR2 is the reporter gene, and TUSC2 is a therapeutic gene. Mice
      with A549 NSCLC lung tumors were injected intravenously with CMV-SSTR2, CMV-TUSC2
      IRES-SSTR2, or CMV-TUSC2 plasmids in DOTAP:cholesterol-liposomal nanoparticles.
      Two days later, mice were injected intravenously with 111In-octreotide. The next
      day, biodistribution was performed. The experiment was repeated including single
      photon emission computed tomography/computed tomography (SPECT/CT).
      Immunohistochemistry was performed. In vitro, SSTR2 expression was similar in
      cells transfected with CMV-SSTR2 or CMV-TUSC2-IRES-SSTR2. TUSC2 expression was
      similar in cells transfected with CMV-TUSC2 or CMV-TUSC2-SSTR2. Biodistribution
      demonstrated significantly greater 111In-octreotide uptake in tumors from mice
      injected with CMV-TUSC2-IRES-SSTR2 or CMV-SSTR2 than the control plasmid, CMV
      TUSC2 (p < .05). Gamma-camera and SPECT/CT imaging illustrated SSTR2 expression
      in tumors in mice injected with CMV-TUSC2-IRES-SSTR2 or CMV-SSTR2 versus
      background with control plasmid. Immunohistochemistry corresponded with imaging.
      SSTR2-based reporter imaging can visualize gene expression in lung tumors after
      systemic liposomal nanoparticle delivery of plasmid containing SSTR2-based
      reporter gene or SSTR2 linked to a second therapeutic gene, such as TUSC2.

PMID- 23962696
TI  - Mild phenotype of Charcot-Marie-Tooth disease type 4B1.
AB  - Charcot-Marie-Tooth type 4B1 (CMT4B1) is a rare autosomal recessive demyelinating
      neuropathy caused by mutation of the myotubularin-related 2 (MTMR2) gene. It is
      characterized by a severe early-onset motor and sensory neuropathy, and myelin
      outfoldings on nerve biopsy. We describe a mild phenotype of CMT4B1 in a Japanese
      patient. She noticed difficulty in walking as an initial symptom at age 13. Her
      symptoms progressed slowly, and she could still walk at age 34. There was no
      cranial neuropathy. A nerve conduction study demonstrated demyelinating
      neuropathy. Sural nerve biopsy revealed a moderate-to-severe loss of myelinated
      fibers, and many focally folded myelin sheaths. Electron micrographs showed
      myelin outfoldings and infoldings. DNA tests for CMT showed that she is a
      homozygote for the MTMR2 p.R628PfsX18 mutation. The mild phenotype in our patient
      is probably due to the C-terminal position of the frame-shift mutation in MTMR2. 

PMID- 23962697
TI  - Gait and six-minute walk performance in persons with multiple sclerosis.
AB  - The six-minute walk (6 MW) has been established as a clinic-based, performance
      measure of walking endurance that reflects community ambulation in multiple
      sclerosis (MS). Consequently, identifying the contribution of variables to 6 MW
      performance may provide targets for improving real-life walking in MS, and these
      variables may differ as a function of disability. This study examined cadence and
      stride length as gait variables that explain differences in 6 MW performance
      between persons with MS and controls, and by level of disability. 256 community
      residing persons with MS and 49 non-MS controls performed a standard 6 MW test
      and completed 2 trials of comfortable walking on an electronic walkway for
      quantifying gait. Regression analyses indicated that cadence and stride length
      explain differences in 6 MW performance between MS and controls, and by level of
      disability in MS. The contribution of cadence and stride length to walking
      endurance differed as a function of disability, such that cadence and to a
      greater extent stride length explained variance in 6 MW performance in mild MS,
      whereas cadence and stride length explained approximately an equivalent amount of
      variance in 6 MW performance in moderate-to-severe MS. We provide evidence for
      intervention strategies that are specific to disability level to improve walking
      endurance in MS.

PMID- 23962698
TI  - Effect of neck flexion on somatosensory and motor evoked potentials in Hirayama
      disease.
AB  - Hirayama disease (HD) is a rare motor disorder mainly affecting young men,
      characterized by atrophy and weakness of forearm and hand muscles corresponding
      to a C7-T1 myotome distribution. The weakness is usually unilateral or asymmetric
      and progression usually stops within several years. The etiology of HD is not
      well understood. One hypothesis, mainly based on MRI findings, is that the
      weakness is a consequence of cervical flexion myelopathy. The aim of this study
      was to explore the function of corticospinal and ascending somatosensory pathways
      during neck flexion using evoked responses. MATERIALS AND METHODS: 15 men with HD
      and 7 age-matched control male subjects underwent somatosensory evoked potentials
      (SSEP) and motor evoked potentials (MEP) studies with the neck in neutral
      position and fully flexed. SSEP studies included electrical stimulation of median
      and ulnar nerves at the wrist, and tibial nerve at the ankle with recording over
      the ipsilateral Erb's point, cervical spine, and contralateral sensory cortex.
      MEP recordings were obtained by magnetic stimulation of the motor cortex and the
      cervical lower spinal roots; the evoked responses were recorded from the
      contralateral thenar and abductor hallucis muscles. RESULTS: MEP recordings
      demonstrated significant lower amplitudes, and slightly prolonged latencies in HD
      patients on cervical stimulation, compared to control subjects. During neck
      flexion, MEP studies also demonstrated a statistically significant drop in mean
      upper limb amplitude on cervical stimulation in HD patients, as well as in
      control subjects, although to a lesser degree. In contrast, no significant
      differences were found in SSEP studies in HD patients compared to control
      subjects, or between neutral and flexed position in these groups. CONCLUSION: The
      study shows a negative effect of cervical flexion on MEP amplitudes in HD
      patients as well as in control subjects, requiring more studies to investigate
      its significance. Neck flexion did not have an influence on any SSEP parameters
      in patients or controls.

PMID- 23962699
TI  - Fukushima radionuclides at air filter and rain water samples collected from
      Istanbul and their atmospheric removal time.
AB  - Accident at Fukushima Daiichi Nuclear Power Plant (FDNPP) is one of the most
      serious accident in the world after Chernobyl accident. Following the continuing
      release of radionuclides in air after FDNPP, traces of fission products ((131)I,
      (134)Cs and (137)Cs) were recorded in the air filter and rain water samples
      collected from the CNAEM area at Istanbul on 4 April 2011. Airborne particle
      samples were collected daily in air filters and radio assayed with a high purity
      germanium detector. The fission products (131)I, (134)Cs and (137)Cs were
      measured with the maximum activity concentrations of 1.03+/-0.08, 0.25+/-0.03 and
      0.23+/-0.03 mBq m(-3), respectively. For determination of the origin of the
      releases the (134)Cs/(137)Cs ratio was calculated between 1.09 and 0.85. The
      authors find removal times for (137)Cs of 8.13 d, (134)Cs of 7.25 d and (131)I of
      6.82 d. 

PMID- 23962700
TI  - Preoperative hypoalbuminemia is an independent predictor of poor perioperative
      outcomes in women undergoing open surgery for gynecologic malignancies.
AB  - OBJECTIVE: To quantify the impact of preoperative hypoalbuminemia on 30-day
      mortality and morbidity after gynecologic cancer surgery. METHODS: Patients
      included in the National Surgical Quality Improvement Program (NSQIP) dataset who
      underwent any non-emergent surgery for gynecologic malignancy between 1/1/2008
      and 12/31/2010 were identified. Analysis was conducted with albumin both as a
      dichotomous variable (<3.5 g/dl was defined as low albumin) and as a continuous
      variable to determine a clinically relevant cut-off value. RESULTS: Of the total
      3171 patients identified, 2110 had preoperative albumin levels available for
      analysis. In addition, 279 (13.3%) of these patients had low albumin levels.
      According to multivariate analysis, the low albumin group had significantly
      higher odds of developing one or more post-operative complications (OR-2,CI: 1.47
      2.73, p<0.0001), three or more complications (OR-4.1,CI: 2.31-7.1, p<0.0001),
      surgical complications (OR-2.39,CI: 1.59-3.58, p<0.0001), thromboembolic
      complications (OR-2.59,CI: 1.33-5.06, p<0.0001), pulmonary complications (OR
      4.06,CI: 2.05-8.03, p<0.0001), or infectious complications (OR-1.84,CI: 1.26
      2.69, p<0.0001) and a higher 30-day mortality (OR-6.52,CI: 2.51-16.95, p<0.0001).
      Upon subgroup analysis, this difference was not found in patients undergoing
      laparoscopic surgery. In patients undergoing open surgery, the probability of
      experiencing one or more post-operative complications increased linearly with the
      decrease in albumin level; however, the probability of patients experiencing
      three or more complications and 30-day mortality increased sharply as soon as the
      albumin level decreased below 3g/dl. CONCLUSION: Preoperative albumin levels
      <3g/dL identify a population of patients at a very high-risk of experiencing
      perioperative morbidity and 30-day mortality after open surgery.

PMID- 23962701
TI  - Distinct molecular features of colorectal cancer in Ghana.
AB  - OBJECTIVES: While colorectal cancer (CRC) is common, its incidence significantly
      varies around the globe. The incidence of CRC in West Africa is relatively low,
      but it has a distinctive clinical pattern and its molecular characteristics have
      not been studied. This study is one of the first attempts to analyze molecular,
      genetic, and pathological characteristics of colorectal cancer in Ghana. METHODS:
      DNA was extracted from microdissected tumor and adjacent normal tissue of 90
      paraffin blocks of CRC cases (1997-2007) collected at the University of Ghana.
      Microsatellite instability (MSI) was determined using fragment analysis of ten
      microsatellite markers. We analyzed expression of mismatch repair (MMR) proteins
      by immunohistochemistry and sequenced exons 2 and 3 of KRAS and exon 15 of BRAF.
      RESULTS: MSI analysis showed 41% (29/70) MSI-High, 20% (14/70) MSI-Low, and 39%
      (27/70) microsatellite-stable (MSS) tumors. Sequencing of KRAS exons 2 and 3
      identified activating mutations in 32% (24/75) of tumors, and sequencing of BRAF
      exon 15, the location of the common activating mutation (V600), did not show
      mutations at codons 599 and 600 in 88 tumors. CONCLUSIONS: Our study found a high
      frequency of MSI-High colorectal tumors (41%) in Ghana. While the frequency of
      KRAS mutations is comparable with other populations, absence of BRAF mutations is
      intriguing and would require further analysis of the molecular epidemiology of
      CRC in West Africa.

PMID- 23962702
TI  - Clinical and radiological features of breast tumors according to history of false
      positive results in mammography screening.
AB  - BACKGROUND: Women with a false-positive result after a screening mammogram have
      an increased risk of cancer detection in subsequent participations, especially
      after assessments involving cytology or biopsy. We aimed to compare women's
      personal characteristics, tumoral features and the radiological appearance of
      cancers with and without a previous false-positive result generated by additional
      imaging or invasive procedures. METHODS: From 1996 to 2007, 111,098 women aged 45
      69 years participated in four population-based breast cancer screening programs
      in Spain, and 1281 cancers were detected. We included all cancers detected in
      subsequent screenings (n=703) and explored the occurrence of previous false
      positive results. We identified false-positives requiring additional imaging or
      invasive procedures. Differences on tumoral features (invasiveness, tumor size,
      and lymph node status) and radiological appearance were assessed by Chi-square
      test, and agreement between the location of cancer and prior suspicious by
      Cohen's kappa coefficient. A multivariate analysis was preformed to evaluate the
      effect of previous screening results and age on the odds of presenting an in situ
      carcinoma. RESULTS: Among the 703 cancers detected in subsequent screenings, 148
      women (21.1%) had a previous false-positive result. Of these, 105 were by
      additional imaging and 43 by invasive procedures. Women with prior false-positive
      result requiring invasive assessment, compared to women with negative tests, and
      women with prior false-positive requiring additional imaging, had a higher
      proportion of in situ carcinomas (31.7%, 15.3%, 12.9%, respectively; p=0.014) and
      microcalcifications (37.2%, 20.2%, 9.5%, respectively; p=0.003). The proportion
      of in situ carcinomas was even higher in women over 60 years (39.2%, 12.5%,
      13.0%, respectively; p=0.001). Ipsilateral cancer was observed in 65.7% of cases
      with prior cytology or biopsy (k=0.479; 95%CI: 0.330-0.794). CONCLUSION: A large
      number of in situ malignancies and calcification patterns were found among women
      with prior false-positive result in mammography screening requiring cytology or
      biopsies, suggesting progression from a previously benign lesion.

PMID- 23962703
TI  - Natural feed contaminant zearalenone decreases the expressions of important pro-
      and anti-inflammatory mediators and mitogen-activated protein kinase/NF-kappaB
      signalling molecules in pigs.
AB  - Zearalenone (ZEA) is an oestrogenic mycotoxin produced by Fusarium species,
      considered to be a risk factor from both public health and agricultural
      perspectives. In the present in vivo study, a feeding trial was conducted to
      evaluate the in vivo effect of a ZEA-contaminated diet on immune response in
      young pigs. The effect of ZEA on pro-inflammatory (TNF-alpha, IL-8, IL-6, IL
      1beta and interferon-gamma) and anti-inflammatory (IL-10 and IL-4) cytokines and
      other molecules involved in inflammatory processes (matrix metalloproteinases
      (MMP)/tissue inhibitors of matrix metalloproteinases (TIMP), nuclear receptors:
      PPARgamma and NF-kappaB1, mitogen-activated protein kinases (MAPK): mitogen
      activated protein kinase kinase kinase 7 (TAK1)/mitogen-activated protein kinase
      14 (p38alpha)/mitogen-activated protein kinase 8 (JNK1)/ mitogen-activated
      protein kinase 9 (JNK2)) in the liver of piglets was investigated. The present
      results showed that a concentration of 316 parts per billion ZEA leads to a
      significant decrease in the levels of pro- and anti-inflammatory cytokines at
      both gene expression and protein levels, correlated with a decrease in the levels
      of other inflammatory mediators, MMP and TIMP. The results also showed that
      dietary ZEA induces a dramatic reduction in the expressions of NF-kappaB1 and
      TAK1/p38alpha MAPK genes in the liver of the experimentally intoxicated piglets,
      and has no effect on the expression of PPARgamma mRNA. The present results
      suggest that the toxic action of ZEA begins in the upstream of the MAPK
      signalling pathway by the inhibition of TAK1, a MAPK/NF-kappaB activator. In
      conclusion, the present study shows that ZEA alters several important parameters
      of the hepatic cellular immune response. From an economic point of view, these
      data suggest that, in pigs, ZEA is not only a powerful oestrogenic mycotoxin but
      also a potential hepatotoxin when administered through the oral route. Therefore,
      the present results represent additional data from cellular and molecular levels
      that could be taken into account in the determination of the regulation limit of
      the tolerance to ZEA. 

PMID- 23962704
TI  - Au-ionic liquid functionalized reduced graphene oxide immunosensing platform for
      simultaneous electrochemical detection of multiple analytes.
AB  - In this work, an Au-ionic liquid functionalized reduced graphene oxide
      nanocomposite (IL-rGO-Au) was fabricated via the self-assembly of ionic liquid
      functionalized reduced graphene oxide (IL-rGO) and gold nanoparticles (AuNPs) by
      electrostatic interaction. The IL-rGO can be synthesized and stabilized by
      introducing the cations of the amine-terminated ionic liquids (IL-NH2) into the
      graphene oxide (GO). With the assistance of IL-NH2, AuNPs were uniformly and
      densely absorbed on the surfaces of the IL-rGO. The proposed IL-rGO-Au
      nanocomposite can be used as an immunosensing platform because it can not only
      facilitate the electrons transfer of the electrode surface but also provide a
      large accessible surface area for the immobilization of abundant antibody. To
      assess the performance of the IL-rGO-Au nanocomposite, a sandwich-type
      electrochemical immunosensor was designed for simultaneous multianalyte detection
      (carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) as model analytes).
      The chitosan (CS) coated prussian blue nanoparticles (PBNPs) or cadmium
      hexacyanoferrate nanoparticles (CdNPs) and loaded with AuNPs were used as
      distinguishable signal tags. The resulting immunosensor exhibited high
      selectivity and sensitivity in simultaneous determination of CEA and AFP in a
      single run. The linear ranges were from 0.01 to 100 ng mL(-1) for both CEA and
      AFP. The detection limits reached 0.01 ng mL(-1) for CEA and 0.006 ng mL(-1) for
      AFP, respectively. No obvious nonspecific adsorption and cross-talk was observed
      during a series of analyses to detect target analytes. In addition, for the
      detection of clinical serum samples, it is well consistent with the data
      determined by the ELISA, indicating that the immunosensor provides a possible
      application for the simultaneous multianalyte determination of CEA and AFP in
      clinical diagnostics.

PMID- 23962705
TI  - Ultrasensitive electrochemical cocaine biosensor based on reversible DNA
      nanostructure.
AB  - We proposed an ultrasensitive electrochemical cocaine biosensor based on the
      three-dimensional (3D) DNA structure conversion of nanostructure from Triangular
      Pyramid Frustum (TPFDNA) to Equilateral Triangle (ETDNA). The presence of cocaine
      triggered the aptamer-composed DNA nanostructure change from "Close" to "Open",
      leading to obvious faradaic impedance changes. The unique properties with
      excellent stability and specific rigid structure of the 3D DNA nanostructure made
      the biosensing functions stable, sensitive, and regenerable. The Faradaic
      impedance responses were linearly related to cocaine concentration between 1.0 nM
      and 2.0 MUM with a correlation coefficient of 0.993. The limit of detection was
      calculated to be 0.21 nM following IUPAC recommendations (3Sb/b). It is expected
      that the distinctive features of DNA nanostructure would make it potentially
      advantageous for a broad range of biosensing, bionanoelectronics, and therapeutic
      applications.

PMID- 23962706
TI  - Iron oxide/gold core/shell nanomagnetic probes and CdS biolabels for amplified
      electrochemical immunosensing of Salmonella typhimurium.
AB  - There is an imminent need for rapid methods to detect and determine pathogenic
      bacteria in food products as alternatives to the laborious and time-consuming
      culture procedures. In this work, an electrochemical immunoassay using iron/gold
      core/shell nanoparticles (Fe@Au) conjugated with anti-Salmonella antibodies was
      developed. The chemical synthesis and functionalization of magnetic and gold
      coated magnetic nanoparticles is reported. Fe@Au nanoparticles were
      functionalized with different self-assembled monolayers and characterized using
      ultraviolet-visible spectrometry, transmission electron microscopy, and
      voltammetric techniques. The determination of Salmonella typhimurium, on screen
      printed carbon electrodes, was performed by square-wave anodic stripping
      voltammetry through the use of CdS nanocrystals. The calibration curve was
      established between 1*10(1) and 1*10(6) cells/mL and the limit of detection was
      13 cells/mL. The developed method showed that it is possible to determine the
      bacteria in milk at low concentrations and is suitable for the rapid (less than
      1h) and sensitive detection of S. typhimurium in real samples. Therefore, the
      developed methodology could contribute to the improvement of the quality control
      of food samples.

PMID- 23962707
TI  - Graphene sheets, polyaniline and AuNPs based DNA sensor for electrochemical
      determination of BCR/ABL fusion gene with functional hairpin probe.
AB  - A sensitive and selective electrochemical DNA sensor was developed for the
      detection of BCR/ABL fusion gene in chronic myelogenous leukemia (CML). Firstly,
      graphene sheets (GS) suspension was prepared with the aid of chitosan (CS)
      solution and then fabricated onto the glassy carbon electrode (GCE), followed by
      the electro-polymerization of aniline to form the PANI layer, then, Au
      nanoparticles (AuNPs) were electro-deposited onto the modified GCE to immobilize
      the capture probes. The capture probe employed a hairpin structure and dually
      labeled with a 5'-SH and a 3'-biotin. After hybridization with the target DNA,
      hairpin structure was compelled to open and 3'-biotin was forced to stay away
      from the electrode surface. As a result, streptavidin-alkaline phosphatase (SA
      AP) was covalently binded to the capture probe via biotin-avidin system.
      Reduction currents were then generated after catalyzing the hydrolysis of the
      electroinactive 1-naphthyl phosphate (1-NP) to 1-naphthol and monitored by
      differential pulse voltammetry (DPV). Under optimum conditions, the amperometric
      signals increased linearly with the target DNA concentrations (10 pM to 1000 pM),
      and the DNA sensor exhibited a detection limit as low as 2.11 pM (S/N=3) with an
      excellent differentiation ability, and the proposed method showed acceptable
      stability and reproducibility. It has been applied for assay of BCR/ABL fusion
      gene from real samples with satisfactory results.

PMID- 23962708
TI  - Competitive electrochemical immunoassay for detection of beta-amyloid (1-42) and
      total beta-amyloid peptides using p-aminophenol redox cycling.
AB  - beta-Amyloid (1-42) peptide (Abeta(1-42)) is believed to be important for
      diagnosis and prognosis of Alzheimer's disease (AD) serving as a reliable
      molecular biomarker. However, the levels of Abeta(1-42) may differ by gender and
      age; thus, assay of Abeta(1-42) only might be unable to discriminate between AD
      and health or other types of dementia. In this work, we reported a sensitive and
      selective electrochemical method for detection of both Abeta(1-42) and total
      Abeta using p-aminophenol (p-AP) redox cycling on antibody-modified gold
      electrodes. Specifically, the conjugates performed between streptavidin
      conjugated alkaline phosphatase (SA-ALP) and biotinylated Abeta peptides were
      captured by the antibody-modified electrodes, which induced the production of
      electrochemically active p-AP from the p-aminophenyl phosphate (p-APP) substrate.
      In the presence of tris(2-carboxyethyl)phosphine (TCEP), p-AP could be cycled
      after its electro-oxidization on the electrode, enabling the increase of the
      anodic current. Because native Abeta competed with the conjugates to bind the
      anchored antibody, the signal decreased with the increase of native Abeta
      concentration. A detection limit of 5 pM was achieved. To demonstrate the
      viability of the method for analysis of Abeta(1-42) and total Abeta in real
      sample, artificial cerebrospinal fluid (aCSF) containing Abeta(1-40), Abeta(1-42)
      and Abeta(1-16) was tested. We believe that the simultaneous detection of Abeta(1
      42) and total Abeta would be valuable for the early diagnosis of AD.

PMID- 23962709
TI  - Highly sensitive enumeration of circulating tumor cells in lung cancer patients
      using a size-based filtration microfluidic chip.
AB  - Circulating tumor cells (CTCs) in the peripheral blood could serve as a surrogate
      marker for the diagnosis of cancer metastasis and for therapeutic evaluation.
      However, the separation and characterization of CTCs is technically challenging
      owing to the extremely low number of CTCs present. Here we developed a size-based
      and high-throughput microfluidic chip, which exploits filtration microchannels to
      isolate the relatively larger CTCs from the rest of the blood constituents. High
      isolation efficiency of our microfluidic chip was demonstrated with three lung
      cancer cell lines spiked in blood samples at an optimal flow rate of 0.4 mL/h.
      The average recovery rates of 96%, 95% and 92% were obtained for A549, SK-MES-1,
      and H446, respectively. To clinically validate the chip, we also employed it to
      isolate CTCs from 59 lung cancer patients. CTCs were detected in 96.7% of
      patients with the mean number of 18.6 cells/mL, which was significantly higher
      than normal controls (P<0.05). The work here indicates that the size-based
      microfluidic platform with the advantage of capturing tumor cells without
      reliance on cell surface expression markers can provide a novel, inexpensive and
      effective tool for CTC detection and evaluation of cancer status.

PMID- 23962710
TI  - Nanoparticle-catalyzed reductive bleaching for fabricating turn-off and enzyme
      free amplified colorimetric bioassays.
AB  - Nanoparticle-catalyzed reductive bleaching reactions of colored substrates are
      emerging as a class of novel indicator reactions for fabricating enzyme-free
      amplified colorimetric biosensing (turn-off mode), which are exactly opposite to
      the commonly used oxidative coloring processes of colorless substrates in
      traditional enzyme-catalyzed amplified colorimetric bioassays (turn-on mode). In
      this work, a simple theoretical analysis shows that the sensitivity of this
      colorimetric bioassay can be improved by increasing the amplification factor
      (kcatDeltat), or enhancing the binding affinity between analyte and receptor
      (Kd), or selecting the colored substrates with high extinction coefficients
      (epsilon). Based on this novel strategy, we have developed a turn-off and cost
      effective amplified colorimetric thrombin aptasensor. This aptasensor made full
      use of sandwich binding of two affinity aptamers for increased specificity,
      magnetic particles for easy separation and enrichment, and gold nanoparticle
      (AuNP)-catalyzed reductive bleaching reaction to generate the amplified
      colorimetric signal. With 4-nitrophenol (4-NP) as the non-dye colored substrate,
      colorimetric bioassay of thrombin was achieved by the endpoint method with a
      detection limit of 91pM. In particular, when using methylene blue (MB) as the
      substrate, for the first time, a more convenient and efficient kinetic-based
      colorimetric thrombin bioassay was achieved without the steps of acidification
      termination and magnetic removal of particles, with a low detection limit of
      10pM, which was superior to the majority of the existing colorimetric thrombin
      aptasensors. The proposed colorimetric protocol is expected to hold great promise
      in field analysis and point-of-care applications. 

PMID- 23962711
TI  - The putative metabolic role of d-chiro inositol phosphoglycan in human pregnancy
      and preeclampsia.
AB  - Immunological alterations, systemic inflammation, endothelial dysfunction, and
      insulin resistance are prominent features of preeclampsia, although the
      reciprocal relationship between them is poorly understood. The metabolic syndrome
      that occurs during preeclampsia can be exacerbated by the systemic inflammation
      and linked to placental metabolism/development and endothelial dysfunction. Under
      healthy conditions, insulin and insulin-like growth factor-integrated pathways
      not only promote cell metabolism and proliferation, but also regulate endothelial
      synthesis and release of vasodilators (e.g., nitric oxide, NO) and opposing
      vasoconstrictors (e.g., endothelin-1) to maintain vascular homeostasis. d-chiro
      inositol phosphoglycans (DCI), second messengers of insulin, are increased during
      preeclampsia and contribute directly to insulin resistance. The dynamic balanced
      control of vascular function may be altered by excessive DCI that impairs the PI3
      kinase-dependent pathway and may result in reduced bioavailability of NO,
      contributing to elevated peripheral vascular resistance and hypertension. 

PMID- 23962712
TI  - Urinary inositol phosphoglycan-P type: near patient test to detect preeclampsia
      prior to clinical onset of the disease. A study on 416 pregnant Mauritian women.
AB  - Preeclampsia and eclampsia account for major pregnancy complications in
      Mauritius, an emerging country (maternal mortality rate of 60 per 100,000
      deliveries). This prospective longitudinal study was carried out in the main
      regional hospital in the north of the island, to measure inositol phosphoglycan-P
      type (IPG-P) in the urine of pregnant women (using an ELISA-based assay). Women
      had approximately 10 prenatal visits per pregnancy and a complete follow-up in
      this same referral centre after the first trimester of pregnancy. Urine samples
      were collected every 1-4 weeks in all women. In a cohort of 416 patients,
      preeclampsia (PE) was diagnosed in 34 women. In established PE (hypertension and
      proteinuria), the assay as a diagnostic test showed a positive likelihood ratio
      of 18.73, a negligible negative likelihood ratio with area under the curve (AUC)
      of 0.99, sensitivity of 96.7%, specificity of 94.8% and remained negative in
      control women (n=312), women with gestational hypertension (without proteinuria
      (n=56), and gestational diabetic mothers (n=14). Moreover, as a predictive
      screening test two weeks before the diagnosis of PE, the assay showed sensitivity
      of 84.2% and specificity of 83.6%. Detection of urinary inositol phosphoglycan-P
      type in pregnant women can be a useful confirmatory marker of PE, as well as a
      predictive marker, two weeks before the onset of the disease. 

PMID- 23962714
TI  - Technological progress and challenges towards cGMP manufacturing of human
      pluripotent stem cells based therapeutic products for allogeneic and autologous
      cell therapies.
AB  - Recent technological advances in the generation, characterization, and
      bioprocessing of human pluripotent stem cells (hPSCs) have created new hope for
      their use as a source for production of cell-based therapeutic products. To date,
      a few clinical trials that have used therapeutic cells derived from hESCs have
      been approved by the Food and Drug Administration (FDA), but numerous new hPSC
      based cell therapy products are under various stages of development in cell
      therapy-specialized companies and their future market is estimated to be very
      promising. However, the multitude of critical challenges regarding different
      aspects of hPSC-based therapeutic product manufacturing and their therapies have
      made progress for the introduction of new products and clinical applications very
      slow. These challenges include scientific, technological, clinical, policy, and
      financial aspects. The technological aspects of manufacturing hPSC-based
      therapeutic products for allogeneic and autologous cell therapies according to
      good manufacturing practice (cGMP) quality requirements is one of the most
      important challenging and emerging topics in the development of new hPSCs for
      clinical use. In this review, we describe main critical challenges and highlight
      a series of technological advances in all aspects of hPSC-based therapeutic
      product manufacturing including clinical grade cell line development, large-scale
      banking, upstream processing, downstream processing, and quality assessment of
      final cell therapeutic products that have brought hPSCs closer to clinical
      application and commercial cGMP manufacturing. 

PMID- 23962713
TI  - Consensus and variations in opinions on delirium care: a survey of European
      delirium specialists.
AB  - BACKGROUND: There are still substantial uncertainties over best practice in
      delirium care. The European Delirium Association (EDA) conducted a survey of its
      members and other interested parties on various aspects of delirium care.
      METHODS: The invitation to participate in the online survey was distributed among
      the EDA membership. The survey covered assessment, treatment of hyperactive and
      hypoactive delirium, and organizational management. RESULTS: A total of 200
      responses were collected (United Kingdom 28.6%, Netherlands 25.3%, Italy 15%,
      Switzerland 9.7%, Germany 7.1%, Spain 3.8%, Portugal 2.5%, Ireland 2.5%, Sweden
      0.6%, Denmark 0.6%, Austria 0.6%, and others 3.2%). Most of the responders were
      doctors (80%), working in geriatrics (45%) or internal medicine (14%). Ninety-two
      per cent of the responders assessed patients for delirium daily. The most
      commonly used assessment tools were the Confusion Assessment Method (52%) and the
      Delirium Observation Screening Scale (30%). The first-line choice in the
      management of hyperactive delirium was a combination of non-pharmacological and
      pharmacological approaches (61%). Conversely, non-pharmacological management was
      the first-line choice in hypoactive delirium (67%). Delirium awareness (34%),
      knowledge (33%), and lack of education (13%) were the most commonly reported
      barriers to improving the detection of delirium. Interestingly, 63% of the
      responders referred patients after an episode of delirium to a follow-up clinic.
      CONCLUSIONS: This is the first systematic survey involving an international group
      of specialists in delirium. Several areas of lack of consensus were found. These
      results emphasise the importance of further research to improve care of this
      major unmet medical need.

PMID- 23962715
TI  - Mode of delivery and its influence on women's satisfaction with childbirth.
AB  - OBJECTIVE: Many factors affect women's satisfaction with the experience of
      childbirth. Some of these are known, but most have not been fully evaluated. The
      influence of the mode of delivery is unclear. This study investigated the extent
      to which satisfaction with childbirth depends on the mode of delivery, and
      evaluated factors determining postpartum satisfaction. STUDY DESIGN: Women with
      singleton pregnancies at term were included prospectively. After childbirth, all
      women meeting the inclusion criteria received a standardised questionnaire - the
      German version of Salmon's Item List (SIL-Ger) - for completion before discharge
      to evaluate the birth experience. The chi-squared test, Fisher's exact test, and
      Kruskal-Wallis test were used for statistical analysis. Univariate and
      multivariate linear regression analyses were used to assess associations between
      demographic and pregnancy-associated variables and variables influencing the
      perception of childbirth in the total SIL-Ger score. Univariate and multivariate
      binary logistic regression models were used to evaluate effects of demographic
      and clinical parameters on SIL-Ger scores of <70 versus SIL-Ger scores of >= 70.
      All covariates with a P value <= 0.10 in the univariate analysis were included in
      multivariate logistic regression models. All tests were two-sided, and P
      values<0.05 were considered statistically significant. RESULTS: The analysis
      included 335 questionnaires. No differences were observed between different modes
      of delivery (normal 84.5 +/- 14.6, primary caesarean 87.0 +/- 13.5, secondary
      caesarean 83.2 +/- 13.8, emergency caesarean 79.3 +/- 7.3, operative vaginal
      delivery 83.9 +/- 13.6; P=0.503). Multivariate analysis identified two
      independent factors associated with higher SIL-Ger scores: good/very good
      satisfaction with childbirth (P<0.001) and good/very good involvement in decision
      making afterwards (P=0.005). Severe pain perception during childbirth was
      associated with lower SIL-Ger scores (P=0.003). Absence of a person of trust
      during childbirth was linked with scores<70 (P=0.005), indicating a negative
      experience. Good/very good satisfaction with childbirth (P<0.001) reduced the
      probability of a score<70. CONCLUSION: Mode of delivery does not directly
      influence women's satisfaction with childbirth. Involvement in decision-making,
      support during labour and effective analgesia appear to be the most important
      factors that improve women's birth experience.

PMID- 23962716
TI  - Pharmaceutical potential of a fucoidan-like sulphated polysaccharide isolated
      from Halodule pinifolia.
AB  - In continuation with the screening of biological properties of seagrasses, we
      isolated sulphated polysaccharides from Halodule pinifolia. This is the first
      report that indicates the presence of fucoidan-like H. pinifolia crude sulphated
      polysaccharide (HPCSP) that are commonly found in brown algae being present in
      marine angiosperms. Fucoidan-like structures such as beta-mannuronic acid
      residues and sulphate groups were confirmed by Fourier transform infrared (FTIR)
      spectral analysis. There was a high content of uronic acid. The isolated HPCSP
      consisted mainly of total sugar (54.17%), protein (11.06%), carbon (18.25%),
      nitrogen (1.77%), hydrogen (3.62%), C/N ratio (2.04%) and uronic acid (2.61%).
      This isolated HPCSP was further investigated to determine anticoagulant and
      antioxidant activity. The HPCSP had high activity in the total antioxidant assay
      (125.86 mg ascorbic acid equivalents/g), DPPH radical scavenging rate (IC50 value
      2.024 +/- 0.12 MUg/mL), deoxyribose radical scavenging rate (51.82% at 1000
      MUg/mL) and H2O2 radical scavenging rate (IC50 value 6.904 +/- 0.34 MUg/mL). In
      the anticoagulant assay, prolonged clotting time was observed with application of
      HPCSP with increasing concentrations. Further purification and characterization
      process is underway to confirm the structures of HPCSP. From the observed
      results, this fucoidan-like HPCSP could be developed as a new natural source of
      potential antioxidants in the functional food industry.

PMID- 23962717
TI  - Further studies and biological activities of macromolecular protein R
      Phycoerythrin from Portieria hornemannii.
AB  - In the present study, the purified R-Phycoerythrin (R-PE) from a red alga
      Portieria hornemannii was subjected to the analysis of stability under the
      influence of different agents. Among the various inhibitors tested on R-PE EDTA
      at lower concentrations (<1 mM) supported the activity of R-PE. When R-PE was
      exposed to different organic solvents, ethanol supported the activity at the
      maximum followed by acetone, ethyl acetate, chloroform and methanol. Citric acid,
      as a preservative maintained the stability of R-PE both under 0 +/- 5  degrees C
      and 30 +/- 5  degrees C with 59.34% and 56.23% respectively, on 30th day. Thermal
      decomposition of the R-PE began near 60  degrees C. Maximum weight loss was
      occurred between 150  degrees C and 500  degrees C. Complete weight loss was
      recorded around 875  degrees C. Thermal denaturation was observed between 19 
      degrees C and 40  degrees C. Moderate to low antioxidant activities were observed
      in R-PE in relation to total antioxidant activities. After characterization, R-PE
      was taken for in vitro anticancer studies against selected cancer cell lines.
      Further studies involving AO/EB fluorescence staining and phase contrast
      microscope revealed characteristic apoptotic features like cell shrinkage,
      membrane blebbing, and nuclear DNA fragmentation, etc. Likewise, FACS analysis
      revealed the cell cycle distribution pattern of A549 and HepG2 cells.

PMID- 23962718
TI  - Advances in the genomics of common eye diseases.
AB  - Genome-wide association studies (GWAS) and other genomic technologies have
      accelerated the discovery of genes and genomic regions contributing to common
      human ocular disorders with complex inheritance. Age-related macular degeneration
      (AMD), diabetic retinopathy (DR), glaucoma and myopia account for the majority of
      visual impairment worldwide. Over 19 genes and/or genomic regions have been
      associated with AMD. Current investigations are assessing the clinical utility of
      risk score panels and therapies targeting disease-specific pathways. DR is the
      leading cause of blindness in the United States and globally is a major cause of
      vision loss. Genomic investigations have identified molecular pathways associated
      with DR in animal models which could suggest novel therapeutic targets. Three
      types of glaucoma, primary-open-angle glaucoma (POAG), angle-closure glaucoma and
      exfoliation syndrome (XFS) glaucoma, are common age-related conditions. Five
      genomic regions have been associated with POAG, three with angle-closure glaucoma
      and one with XFS. Myopia causes substantial ocular morbidity throughout the
      world. Recent large GWAS have identified >20 associated loci for this condition.
      In this report, we present a comprehensive overview of the genes and genomic
      regions contributing to disease susceptibility for these common blinding ocular
      disorders and discuss the next steps toward translation to effective gene-based
      screening tests and novel therapies targeting the molecular events contributing
      to disease. 

PMID- 23962719
TI  - Promoter histone H3K27 methylation in the control of IGF2 imprinting in human
      tumor cell lines.
AB  - Aberrant imprinting of the insulin-like growth factor II (IGF2) gene is a
      molecular hallmark of many tumors. Reactivation of the normally suppressed
      maternal allele leads to upregulation of the growth factor that promotes tumor
      growth. However, the mechanisms underlying the loss of imprinting (LOI) remain
      poorly defined. We examined the epigenotypes at the gene promoters that control
      IGF2 allelic expression. Using chromatin immunoprecipitation, we found that in
      cells characterized by maintenance of IGF2 imprinting, three IGF2 promoters were
      differentially modified, with the suppressed allele heavily methylated at histone
      H3K27 while the active allele was unmethylated. In the LOI tumors, however, both
      alleles were unmethylated, and correspondingly there was no binding of SUZ12, the
      docking factor of the polycomb repressive complex 2 (PRC2), and of the zinc
      finger-containing transcription factor (CTCF) that recruits the PRC2. Using
      chromatin conformation capture, we found that the CTCF-orchestrated
      intrachromosomal loop between the IGF2 promoters and the imprinting control
      region was abrogated in cells with LOI. SUZ12, which docks the PRC2 to IGF2
      promoters for H3K27 methylation, was downregulated in LOI cells. These data
      reveal a new epigenetic control pathway related to the loss of IGF2 imprinting in
      tumors. 

PMID- 23962721
TI  - Databases of genomic variation and phenotypes: existing resources and future
      needs.
AB  - Massively parallel sequencing (MPS) has become an important tool for identifying
      medically significant variants in both research and the clinic. Accurate
      variation and genotype-phenotype databases are critical in our ability to make
      sense of the vast amount of information that MPS generates. The purpose of this
      review is to summarize the state of the art of variation and genotype-phenotype
      databases, how they can be used, and opportunities to improve these resources.
      Our working assumption is that the objective of the clinical genomicist is to
      identify highly penetrant variants that could explain existing disease or predict
      disease risk for individual patients or research participants. We have detailed
      how current databases contribute to this goal providing frequency data,
      literature reviews and predictions of causation for individual variants. For
      variant annotation, databases vary greatly in their ease of use, the use of
      standard mutation nomenclature, the comprehensiveness of the variant cataloging
      and the degree of expert opinion. Ultimately, we need a dynamic and comprehensive
      reference database of medically important variants that is easily cross
      referenced to exome and genome sequence data and allows for an accumulation of
      expert opinion. 

PMID- 23962720
TI  - A genome-wide association study and biological pathway analysis of epilepsy
      prognosis in a prospective cohort of newly treated epilepsy.
AB  - We present the analysis of a prospective multicentre study to investigate genetic
      effects on the prognosis of newly treated epilepsy. Patients with a new clinical
      diagnosis of epilepsy requiring medication were recruited and followed up
      prospectively. The clinical outcome was defined as freedom from seizures for a
      minimum of 12 months in accordance with the consensus statement from the
      International League Against Epilepsy (ILAE). Genetic effects on remission of
      seizures after starting treatment were analysed with and without adjustment for
      significant clinical prognostic factors, and the results from each cohort were
      combined using a fixed-effects meta-analysis. After quality control (QC), we
      analysed 889 newly treated epilepsy patients using 472 450 genotyped and 6.9 *
      10(6) imputed single-nucleotide polymorphisms. Suggestive evidence for
      association (defined as Pmeta < 5.0 * 10(-7)) with remission of seizures after
      starting treatment was observed at three loci: 6p12.2 (rs492146, Pmeta = 2.1 *
      10(-7), OR[G] = 0.57), 9p23 (rs72700966, Pmeta = 3.1 * 10(-7), OR[C] = 2.70) and
      15q13.2 (rs143536437, Pmeta = 3.2 * 10(-7), OR[C] = 1.92). Genes of biological
      interest at these loci include PTPRD and ARHGAP11B (encoding functions implicated
      in neuronal development) and GSTA4 (a phase II biotransformation enzyme). Pathway
      analysis using two independent methods implicated a number of pathways in the
      prognosis of epilepsy, including KEGG categories 'calcium signaling pathway' and
      'phosphatidylinositol signaling pathway'. Through a series of power curves, we
      conclude that it is unlikely any single common variant explains >4.4% of the
      variation in the outcome of newly treated epilepsy. 

PMID- 23962722
TI  - Acetylation of the KXGS motifs in tau is a critical determinant in modulation of
      tau aggregation and clearance.
AB  - The accumulation of hyperphosphorylated tau in neurofibrillary tangles (NFTs) is
      a neuropathological hallmark of tauopathies, including Alzheimer's disease (AD)
      and chronic traumatic encephalopathy, but effective therapies directly targeting
      the tau protein are currently lacking. Herein, we describe a novel mechanism in
      which the acetylation of tau on KXGS motifs inhibits phosphorylation on this same
      motif, and also prevents tau aggregation. Using a site-specific antibody to
      detect acetylation of KXGS motifs, we demonstrate that these sites are
      hypoacetylated in patients with AD, as well as a mouse model of tauopathy,
      suggesting that loss of acetylation on KXGS motifs renders tau vulnerable to
      pathogenic insults. Furthermore, we identify histone deacetylase 6 (HDAC6) as the
      enzyme responsible for the deacetylation of these residues, and provide proof of
      concept that acute treatment with a selective and blood-brain barrier-permeable
      HDAC6 inhibitor enhances acetylation and decreases phosphorylation on tau's KXGS
      motifs in vivo. As such, we have uncovered a novel therapeutic pathway that can
      be manipulated to block the formation of pathogenic tau species in disease. 

PMID- 23962726
TI  - Application of an automatic adaptive filter for Heart Rate Variability analysis.
AB  - The presence of artifacts and noise effects in temporal series can seriously
      hinder the analysis of Heart Rate Variability (HRV). The tachograms should be
      carefully edited to avoid erroneous interpretations. The physician should
      carefully analyze the tachogram in order to detect points that might be
      associated with unlikely biophysical behavior and manually eliminate them from
      the data series. However, this is a time-consuming procedure. To facilitate the
      pre-analysis of the tachogram, this study uses a method of data filtering based
      on an adaptive filter which is quickly able to analyze a large amount of data.
      The method was applied to 229 time series from a database of patients with
      different clinical conditions: premature newborns, full-term newborns, healthy
      young adults, adults submitted to a very-low-calorie diet, and adults under
      preoperative evaluation for coronary artery bypass grafting. This proposed method
      is compared to the demanding conventional method, wherein the corrections of
      occasional ectopic beats and artifacts are usually manually executed by a
      specialist. To confirm the reliability of the results obtained, correlation
      coefficients were calculated, using both automatic and manual methods of ltering
      for each HRV index selected. A high correlation between the results was found,
      with highly significant p values, for all cases, except for some parameters
      analyzed in the premature newborns group, an issue that is thoroughly discussed.
      The authors concluded that the proposed adaptive filtering method helps to
      efficiently handle the task of editing temporal series for HRV analysis. 

PMID- 23962727
TI  - Ventricular activity cancellation in electrograms during atrial fibrillation with
      constraints on residuals' power.
AB  - During atrial fibrillation (AF), cancellation of ventricular activity from atrial
      electrograms (AEG) is commonly performed by template matching and subtraction
      (TMS): a running template, built in correspondence of QRSs, is subtracted from
      the AEG to uncover atrial activity (AA). However, TMS can produce poor
      cancellation, leaving high-power residues. In this study, we propose to modulate
      the templates before subtraction, in order to make the residuals as similar as
      possible to the nearby atrial activity, avoiding high-power ones. The
      coefficients used to modulate the template are estimated by maximizing, via Multi
      swarm Particle Swarm Optimization, a fitness function. The modulated TMS method
      (mTMS) was tested on synthetic and real AEGs. Cancellation performances were
      assessed using: normalized mean squared error (NMSE, computed on simulated data
      only), reduction of ventricular activity (VDR), and percentage of segments (PP)
      whose power was outside the standard range of the atrial power. All testings
      suggested that mTMS is an improvement over TMS alone, being, on simulated data,
      NMSE and PP significantly decreased while VDR significantly increased. Similar
      results were obtained on real electrograms (median values of CS1 recordings PP:
      2.44 vs. 0.38 p < 0.001; VDR: 6.71 vs. 8.15 p < 0.001).

PMID- 23962725
TI  - Jaw bone marrow-derived osteoclast precursors internalize more bisphosphonate
      than long-bone marrow precursors.
AB  - Bisphosphonates (BPs) are widely used in the treatment of several bone diseases,
      such as osteoporosis and cancers that have metastasized to bone, by virtue of
      their ability to inhibit osteoclastic bone resorption. Previously, it was shown
      that osteoclasts present at different bone sites have different characteristics.
      We hypothesized that BPs could have distinct effects on different populations of
      osteoclasts and their precursors, for example as a result of a different capacity
      to endocytose the drugs. To investigate this, bone marrow cells were isolated
      from jaw and long bone from mice and the cells were primed to differentiate into
      osteoclasts with the cytokines M-CSF and RANKL. Before fusion occurred, cells
      were incubated with fluorescein-risedronate (FAM-RIS) for 4 or 24h and uptake was
      determined by flow cytometry. We found that cultures obtained from the jaw
      internalized 1.7 to 2.5 times more FAM-RIS than long-bone cultures, both after 4
      and 24h, and accordingly jaw osteoclasts were more susceptible to inhibition of
      prenylation of Rap1a after treatment with BPs for 24h. Surprisingly, differences
      in BP uptake did not differentially affect osteoclastogenesis. This suggests that
      jaw osteoclast precursors are less sensitive to bisphosphonates after
      internalization. This was supported by the finding that gene expression of the
      anti-apoptotic genes Bcl-2 and Bcl-xL was higher in jaw cells than long bone
      cells, suggesting that the jaw cells might be more resistant to BP-induced
      apoptosis. Our findings suggest that bisphosphonates have distinct effects on
      both populations of osteoclast precursors and support previous findings that
      osteoclasts and precursors are bone-site specific. This study may help to provide
      more insights into bone-site-specific responses to bisphosphonates. 

PMID- 23962732
TI  - Global deposition of airborne dioxin.
AB  - We present a global dioxin model that simulates one year of atmospheric
      emissions, transport processes, and depositions to the earth's terrestrial and
      marine habitats. We map starting emission levels for each land area, and we also
      map the resulting deposits to terrestrial and marine environments. This model
      confirms that 'hot spots' of deposition are likely to be in northern Europe,
      eastern North America, and in parts of Asia with the highest marine dioxin
      depositions being the northeast and northwest Atlantic, western Pacific, northern
      Indian Ocean and the Mediterranean. It also reveals that approximately 40% of
      airborne dioxin emissions are deposited to marine environments and that many
      countries in Africa receive more dioxin than they produce, which results in these
      countries being disproportionately impacted. Since human exposure to dioxin is
      largely through diet, this work highlights food producing areas that receive
      higher atmospheric deposits of dioxin than others. 

PMID- 23962730
TI  - Best practices for developing cardiovascular quality indicators.
AB  - The Canadian Heart Health Strategy and Action Plan recommended that the Canadian
      Cardiovascular Society (CCS) lead the development of pan-Canadian data
      definitions and quality indicators (QIs) for evaluating cardiovascular care in
      Canada. In response to this recommendation, the CCS developed and adopted a
      standardized QI development methodology. This report provides a brief overview of
      the CCS "Best Practices" for developing pan-Canadian cardiovascular QIs. A more
      detailed description is available in Supplemental Material. The CCS Best
      Practices QI development methodology consists of 3 phases: phase I, plan and
      organize the QI development initiative; phase II, develop and select QIs; and
      phase III, operationalize the QIs. Phase I includes identifying the
      cardiovascular focus or content area, determining the objective and/or purpose of
      the initiative, the target users of, and the target population for, the QIs, and
      selection of a QI working group. Phase II involves formulating the QIs including
      generating a preliminary set of QIs and draft definitions, followed by an
      indicator rating and ranking process based on the CCS QI rating criteria. Phase
      III involves finalizing technical specifications and pilot testing the QIs. It
      also describes the CCS QI approval process and addresses knowledge translation.
      Adoption of a standardized methodology for QI development will improve the
      quality, completeness, acceptability, and usability of pan-Canadian
      cardiovascular QIs developed by the CCS. Public release of the QI definitions and
      related performance data might help improve patient care quality and outcomes. 

PMID- 23962724
TI  - Prion-like nuclear aggregation of TDP-43 during heat shock is regulated by
      HSP40/70 chaperones.
AB  - TDP-43 aggregation in the cytoplasm or nucleus is a key feature of the pathology
      of amyotrophic lateral sclerosis and frontotemporal dementia and is observed in
      numerous other neurodegenerative diseases, including Alzheimer's disease. Despite
      this fact, the inciting events leading to TDP-43 aggregation remain unclear. We
      observed that endogenous TDP-43 undergoes reversible aggregation in the nucleus
      after the heat shock and that this behavior is mediated by the C-terminal prion
      domain. Substitution of the prion domain from TIA-1 or an authentic yeast prion
      domain from RNQ1 into TDP-43 can completely recapitulate heat shock-induced
      aggregation. TDP-43 is constitutively bound to members of the Hsp40/Hsp70 family,
      and we found that heat shock-induced TDP-43 aggregation is mediated by the
      availability of these chaperones interacting with the inherently disordered C
      terminal prion domain. Finally, we observed that the aggregation of TDP-43 during
      heat shock led to decreased binding to hnRNPA1, and a change in TDP-43 RNA
      binding partners suggesting that TDP-43 aggregation alters its function in
      response to misfolded protein stress. These findings indicate that TDP-43 shares
      properties with physiologic prions from yeast, in that self-aggregation is
      mediated by a Q/N-rich disordered domain, is modulated by chaperone proteins and
      leads to altered function of the protein. Furthermore, they indicate that TDP-43
      aggregation is regulated by chaperone availability, explaining the recurrent
      observation of TDP-43 aggregates in degenerative diseases of both the brain and
      muscle where protein homeostasis is disrupted. 

PMID- 23962731
TI  - The emerging role of biomarkers in atrial fibrillation.
AB  - Improved diagnostic techniques have identified various biomarkers that might play
      an important role in prediction of atrial fibrillation (AF) and related outcomes
      (cardio- and cerebrovascular events, and mortality and rhythm outcomes).
      Biomarkers can include blood markers (e.g., von Willebrand factor, D-dimer,
      natriuretic peptides, etc.), urine (e.g., proteinuria, estimated glomerular
      filtration rate, or creatinine clearance), cardiac imaging (echocardiography;
      transthoracic or transoesophageal), or cerebral imaging (e.g., computed
      tomography or magnetic resonance imaging), which can provide additional
      refinement to clinical stroke risk stratification for identification of "high
      risk" subjects. Although inclusion of some blood-based biomarkers (e.g., von
      Willebrand factor, D-dimer) in existing clinical stroke risk stratification
      schemes might improve their predictive value for identifying "high risk"
      patients, this concept might be outdated and overtaken by new developments in
      thromboprophylaxis (which now focus on initial identification of "low risk"
      patients who do not need any antithrombotic therapy, followed by patients with 1
      or more stroke risk factors, to whom anticoagulation can be offered), and
      additional questionable practicality in "everyday" practice. Biomarkers could be
      applied as a "rule out" approach or as surrogates of anticoagulation efficacy in
      trials of new antithrombotic strategies. The present review aims to provide an
      update of the role of biomarkers in AF, with particular focus on AF outcomes.

PMID- 23962733
TI  - Levels and spatial distribution of perfluorinated compounds (PFCs) in superficial
      sediments from the marine reserves of the Tuscan Archipelago National Park
      (Italy).
AB  - Surface sediments from marine reserves of the Tuscan Archipelago National Park
      (Italy), including remote islands not directly affected by anthropogenic
      influences, were analyzed for two dominant perfluorinated compounds (PFCs),
      namely perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA), using LC
      ESI-MS/MS. The concentrations of PFOS were low, with medians ranging from 0.25 to
      1.50 ng/g dry wt, whereas PFOA was always below the detection limit of 0.1 ng/g
      dry wt. The present paper can be considered a baseline study useful in future
      environmental monitoring programs.

PMID- 23962728
TI  - Sodium iron EDTA and ascorbic acid, but not polyphenol oxidase treatment,
      counteract the strong inhibitory effect of polyphenols from brown sorghum on the
      absorption of fortification iron in young women.
AB  - In addition to phytate, polyphenols (PP) might contribute to low Fe
      bioavailability from sorghum-based foods. To investigate the inhibitory effects
      of sorghum PP on Fe absorption and the potential enhancing effects of ascorbic
      acid (AA), NaFeEDTA and the PP oxidase enzyme laccase, we carried out three Fe
      absorption studies in fifty young women consuming dephytinised Fe-fortified test
      meals based on white and brown sorghum varieties with different PP
      concentrations. Fe absorption was measured as the incorporation of stable Fe
      isotopes into erythrocytes. In study 1, Fe absorption from meals with 17 mg PP
      (8.5%) was higher than that from meals with 73 mg PP (3.2%) and 167 mg PP (2.7%;
      P< 0.001). Fe absorption from meals containing 73 and 167 mg PP did not differ
      (P= 0.9). In study 2, Fe absorption from NaFeEDTA-fortified meals (167 mg PP) was
      higher than that from the same meals fortified with FeSO4 (4.6 v. 2.7%; P<
      0.001), but still it was lower than that from FeSO4-fortified meals with 17 mg PP
      (10.7%; P< 0.001). In study 3, laccase treatment decreased the levels of PP from
      167 to 42 mg, but it did not improve absorption compared with that from meals
      with 167 mg PP (4.8 v. 4.6%; P= 0.4), whereas adding AA increased absorption to
      13.6% (P< 0.001). These findings suggest that PP from brown sorghum contribute to
      low Fe bioavailability from sorghum foods and that AA and, to a lesser extent,
      NaFeEDTA, but not laccase, have the potential to overcome the inhibitory effect
      of PP and improve Fe absorption from sorghum foods.

PMID- 23962723
TI  - Hexokinase activity is required for recruitment of parkin to depolarized
      mitochondria.
AB  - Autosomal recessive parkinsonism genes contribute to maintenance of mitochondrial
      function. Two of these, PINK1 and parkin, act in a pathway promoting autophagic
      removal of depolarized mitochondria. Although recruitment of parkin to
      mitochondria is PINK1-dependent, additional components necessary for signaling
      are unclear. We performed a screen for endogenous modifiers of parkin recruitment
      to depolarized mitochondria and identified hexokinase 2 (HK2) as a novel modifier
      of depolarization-induced parkin recruitment. Hexose kinase activity was required
      for parkin relocalization, suggesting the effects are shared among hexokinases
      including the brain-expressed hexokinase 1 (HK1). Knockdown of both HK1 and HK2
      led to a stronger block in parkin relocalization than either isoform alone, and
      expression of HK2 in primary neurons promoted YFP-parkin recruitment to
      depolarized mitochondria. Mitochondrial parkin recruitment was attenuated with
      AKT inhibition, which is known to modulate HK2 activity and mitochondrial
      localization. We, therefore, propose that Akt-dependent recruitment of
      hexokinases is a required step in the recruitment of parkin prior to mitophagy. 

PMID- 23962734
TI  - Modeling visual working memory with the MemToolbox.
AB  - The MemToolbox is a collection of MATLAB functions for modeling visual working
      memory. In support of its goal to provide a full suite of data analysis tools,
      the toolbox includes implementations of popular models of visual working memory,
      real and simulated data sets, Bayesian and maximum likelihood estimation
      procedures for fitting models to data, visualizations of data and fit, validation
      routines, model comparison metrics, and experiment scripts. The MemToolbox is
      released under the permissive BSD license and is available at
      http://memtoolbox.org. 

PMID- 23962735
TI  - The biological significance of color constancy: an agent-based model with bees
      foraging from flowers under varied illumination.
AB  - The perceived color of an object depends on its spectral reflectance and the
      spectral composition of the illuminant. Thus when the illumination changes, the
      light reflected from the object also varies. This would result in a different
      color sensation if no color constancy mechanism is put in place-that is, the
      ability to form consistent representation of colors across various illuminants
      and background scenes. We explore the quantitative benefits of various color
      constancy algorithms in an agent-based model of foraging bees, where agents
      select flower color based on reward. Each simulation is based on 100 "meadows"
      with five randomly selected flower species with empirically determined spectral
      reflectance properties, and each flower species is associated with realistic
      distributions of nectar rewards. Simulated foraging bees memorize the colors of
      flowers that they have experienced as most rewarding, and their task is to
      discriminate against other flower colors with lower rewards, even in the face of
      changing illumination conditions. We compared the performance of von Kries, White
      Patch, and Gray World constancy models with (hypothetical) bees with perfect
      color constancy, and color-blind bees. A bee equipped with trichromatic color
      vision but no color constancy performed only ~20% better than a color-blind bee
      (relative to a maximum improvement at 100% for perfect color constancy), whereas
      the most powerful recovery of reflectance in the face of changing illumination
      was generated by a combination of von Kries photoreceptor adaptation and a White
      Patch calibration (~30% improvement relative to a bee without color constancy).
      However, none of the tested algorithms generated perfect color constancy. 

PMID- 23962736
TI  - Object-based encoding in visual working memory: a life span study.
AB  - Recent studies on development of visual working memory (VWM) predominantly focus
      on VWM capacity and spatial-based information filtering in VWM. Here we explored
      another new aspect of VWM development: object-based encoding (OBE), which refers
      to the fact that even if one feature dimension is required to be selected into
      VWM, the other irrelevant dimensions are also extracted. We explored the OBE in
      children, young adults, and old adults, by probing an "irrelevant-change
      distracting effect" in which a change of stored irrelevant feature dramatically
      affects the performance of task-relevant features in a change-detection task.
      Participants were required to remember two or four simple colored shapes, while
      color was used as the relevant dimension. We found that changes to irrelevant
      shapes led to a significant distracting effect across the three age groups in
      both load conditions; however, children showed a greater degree of OBE than did
      young and old adults. These results suggest that OBE exists in VWM over the life
      span (6-67 years), yet continues to develop along with VWM. 

PMID- 23962737
TI  - Long-lasting visual integration of form, motion, and color as revealed by visual
      masking.
AB  - When two similar visual stimuli are presented in rapid succession at the same
      location, they fuse. For example, a red and a green disk are perceived as one
      single yellow disk. Likewise, verniers with opposite offset directions are
      perceived as one vernier with an almost aligned vernier offset. In fusion,
      observers have no conscious access to the individual stimuli. Using transcranial
      magnetic stimulation (TMS), it has been shown that feature fusion for verniers
      can be modulated for about 400 ms in that either the first or the second vernier
      dominates the percept, depending on TMS onset. Here, we use light masks to
      modulate feature fusion for verniers, motion, and color. Our results are similar
      to the TMS experiment and show that individual visual features are stored for a
      substantial amount of time before they are integrated. 

PMID- 23962738
TI  - Feasibility of customised unipolar conversion using bipolar temporary pacing
      wires in patients after surgical repair of congenital heart disease.
AB  - OBJECTIVE: Temporary pacing wires play a crucial role in the diagnosis and
      therapy of post-operative arrhythmia after surgery for congenital heart disease.
      At present, bipolar pacing wires are used in most institutions. In case of
      functional failure of these wires, a unipolar mode of stimulation and sensing
      should be theoretically possible as a rescue procedure. METHODS: We tested the
      feasibility of the customised unipolar mode in 18 post-operative patients with
      congenital heart disease (age 9.2 +/- 13.9 months, weight 6.3 +/- 3.8 kg, and
      cardiopulmonary bypass time 70 +/- 29 minutes). As there are two possible
      unipolar configurations, there are twice the number of testing parameters; of
      those, we compared sensing (mV) and pacing thresholds (V at 0.5 ms). RESULTS:
      Atrial sensing was significantly better in the unipolar modes (p < 0.001, p <
      0.003). The ventricular unipolar sensing did not differ significantly in the
      "better" of the two possible configurations from the bipolar values (p = 0.363).
      For the unipolar pacing thresholds, only the "better" unipolar configuration did
      not differ significantly from the bipolar measurements (atrial: p = 0.058,
      ventricular: p = 0.138). There was no exit block or undersensing. CONCLUSION: The
      results demonstrate that unipolar stimulation and sensing using bipolar
      epicardial temporary pacing wires is feasible. In the case of failure of bipolar
      temporary pacing wires, this modality represents an easy rescue measure that in
      such cases should always be considered.

PMID- 23962739
TI  - Comorbid Axis I-disorders among subjects with pathological, problem, or at-risk
      gambling recruited from the general population in Germany: results of the PAGE
      study.
AB  - The aim of the present study was to analyze comorbid Axis I-disorders in a sample
      of individuals with at-risk, problem, and pathological gambling. A number of 164
      adult gamblers derived from a random sample of 15,023 individuals were compared
      with a general population sample. The lifetime prevalence of any psychiatric
      disorder was 93.6% among pathological (five-10 criteria), 83.5% among problem
      (three or four criteria), and 81.0% among at-risk gamblers (one or two criteria).
      Substance use disorders were the most common comorbid disorders in gamblers.
      Logistic regression analyses revealed elevated odds ratios for having a comorbid
      disorder in at-risk (Conditional Odds Ratio (COR) 3.5, Confidence Interval (CI)
      2.6-4.6), problem (COR 4.9, CI 3.3-7.3), and pathological gamblers (COR 4.6, CI
      3.0-6.9) compared to the general population. No significant differences were
      found between at-risk and problem gamblers or problem and pathological gamblers.
      Compared to at-risk gamblers, pathological gamblers showed elevated rates of
      comorbid substance use disorders. The data suggest a linear association between
      gambling disorder severity and comorbid Axis I-disorders. In conclusion, comorbid
      disorders are very prevalent in individuals with gambling problems. Even at-risk
      gamblers with one or two DSM-IV criteria show high rates of Axis I-disorders.
      Therefore, this group should be included in further studies on problematic
      gambling. 

PMID- 23962740
TI  - Relationship between early maladaptive schemas and symptom dimensions in patients
      with obsessive-compulsive disorder.
AB  - The aims of this study were to evaluate early maladaptive schemas (EMSs) of
      patients with obsessive-compulsive disorder (OCD) and to clarify relationships
      between particular EMSs and the five factor-analyzed symptom dimensions and other
      clinical variables. Fifty-seven patients with OCD and 70 normal controls
      completed the Young Schema Questionnaire, the Yale-Brown Obsessive Compulsive
      Scale (Y-BOCS), the Y-BOCS symptom checklist, and the Beck Depression Inventory.
      Patients with OCD had significantly higher scores for schema related to
      defectiveness/shame, social isolation/alienation, and failure than did normal
      controls. Among the five OCD symptom dimensions, the sexual/religious dimension
      was only significantly correlated with two schemas of vulnerability to harm or
      illness and enmeshment/undeveloped self. These two schemas were significant
      predictors of the sexual/religious dimension, accounting for 33% of the total
      variance in this dimension. Any EMSs in patients with OCD were not related to
      clinical variables such as severity of OCD and duration of illness. These
      findings may constitute evidence to improve our understandings of OCD from a
      perspective of schema theory. 

PMID- 23962741
TI  - Infection prevention in the ICU: more than just picking one or another preventive
      measure.

PMID- 23962742
TI  - Acquired immunity and vaccination against infectious pancreatic necrosis virus of
      salmon.
AB  - Acquired immunity plays an important role in the protection of salmonids
      vaccinated against infectious pancreatic necrosis virus (IPNV) infections. In
      recent years, vaccine research has taken a functional approach to find the
      correlates of protective immunity against IPNV infections. Accumulating evidence
      suggests that the humoral response, specifically IgM is a correlate of vaccine
      protection against IPNV infections. The role of IgT on the other hand, especially
      at the sites of virus entry into the host is yet to be established. The kinetics
      of CD4+ and CD8+ T-cell gene expression have also been shown to correlate with
      protection in salmonids, suggesting that other arms of the adaptive immune
      response e.g. cytotoxic T cell responses and Th1 may also be important. Overall,
      the mechanisms of vaccine protection observed in salmonids are comparable to
      those seen in other vertebrates suggesting that the immunological basis of
      vaccine protection has been conserved across vertebrate taxa. 

PMID- 23962743
TI  - Identification and functional studies of Akirin, a potential positive nuclear
      factor of NF-kappaB signaling pathways in the Pacific white shrimp, Litopenaeus
      vannamei.
AB  - As conserved nuclear factors, Akirins play critical roles in regulating
      antimicrobial peptides (AMPs) transcription downstream of NF-kappaB dependent
      signaling pathways in insects and mammals. However, no any functional studies was
      reported in penaeid shrimp. The identification and functional analysis of Akirin
      in the Pacific white shrimp, Litopenaeus vannamei were made in this research. The
      833 nucleotides cDNA of Litopenaeus vannamei Akirin (LvAkirin) was obtained with
      an open reading frame of 639 bp, which encodes a putative protein of 212 amino
      acids. The molecular weight of LvAkirin is about 23.7 kDa with theoretical pI of
      9.05. Two predicted nuclear localization signals (NLSs) were found and amino acid
      sequence alignments showed that Akirins are highly conserved between insects and
      mammals. The constitutive expression of LvAkirin mRNA was confirmed in all the
      examined tissues and high level appeared in testis followed by hemocytes and
      gill. LvAkirin mRNA was strongly induced in response to Vibrio parahaemolyticus
      infection. Silencing LvAkirin by dsRNA significantly reduced the expression of NF
      kappaB dependent anti-lipopolysaccharide factor, crustin and penaeidin3a as well
      as transcription factors, Dorsal and Relish post Vibrio anguillarum (V.
      anguillarum) and Micrococcus lysodeikticus (M. lysodeikticus) challenge.
      Antibacterial activities of shrimp plasma was analyzed and high cumulative
      mortality was found in LvAkirin-silenced shrimps post bacteria challenge. Hence,
      we proposed LvAkirin might function as a positive nuclear factor of NF-kappaB
      dependent signaling pathways in shrimp innate immunity.

PMID- 23962744
TI  - Reduced in vitro toxicity of fine particulate matter collected during the 2008
      Summer Olympic Games in Beijing: the roles of chemical and biological components.
AB  - Beijing has implemented systematic air pollution control legislation to reduce
      particulate emissions and improve air quality during the 2008 Summer Olympics,
      but whether the toxicity of fine fraction of particles (PM(2.5)) would be changed
      remains unclear. In present study we compared in vitro biological responses of
      PM(2.5) collected before and during the Olympics and tried to reveal possible
      correlations between its chemical components and toxicological mechanism(s). We
      measured cytotoxicity, cytokines/chemokines, and related gene expressions in
      murine alveolar macrophages, MH-S, after treated with 20 PM(2.5) samples.
      Significant, dose-dependent effects on cell viability, cytokine/chemokine release
      and mRNA expressions were observed. The cytotoxicity caused at equal mass
      concentration of PM(2.5) was notably reduced (p<0.05) by control measures, and
      significant association was found for viability and elemental zinc in PM(2.5).
      Endotoxin content in PM(2.5) correlated with all of the eight detected
      cytokines/chemokines; elemental and organic carbon correlated with four; arsenic
      and chromium correlated with six and three, respectively; iron and barium showed
      associations with two; nickel, magnesium, potassium, and calcium showed
      associations with one. PM(2.5) toxicity in Beijing was substantially dependent on
      its chemical components, and lowering the levels of specific components in
      PM(2.5) during the 2008 Olympics resulted in reduced biological responses.

PMID- 23962745
TI  - Evaluating the potential of IL-27 as a novel therapeutic agent in HIV-1
      infection.
AB  - Interleukin 27 (IL-27) is an immunomodulatory cytokine with important roles in
      both the innate and adaptive immune systems. In the last five years, the addition
      of exogenous IL-27 to primary cell cultures has been demonstrated to decrease HIV
      1 replication in a number of cell types including peripheral blood mononuclear
      cells (PBMCs), CD4+ T cells, macrophages and dendritic cells. These in vitro
      findings suggest that IL-27 may have therapeutic value in the setting of HIV-1
      infection. In this review, we describe the current knowledge of the biology of IL
      27, its effects primarily on HIV-1 replication but also in other viral infections
      and explore its potential role as a therapeutic cytokine for the treatment of
      patients with HIV-1 infection. 

PMID- 23962746
TI  - Impact of bone and liver metastases on patients with renal cell carcinoma treated
      with targeted therapy.
AB  - BACKGROUND: The skeleton and liver are frequently involved sites of metastasis in
      patients with metastatic renal cell carcinoma (RCC). OBJECTIVE: To analyze
      outcomes based on the presence of bone metastases (BMs) and/or liver metastases
      (LMs) in patients with RCC treated with targeted therapy. DESIGN, SETTING, AND
      PARTICIPANTS: We conducted a review from the International Metastatic Renal Cell
      Carcinoma Database Consortium (IMDC) of 2027 patients with metastatic RCC.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We analyzed the impact of the site
      of metastasis on overall survival (OS) and time-to-treatment failure. Statistical
      analyses were performed using multivariable Cox regression. RESULTS AND
      LIMITATIONS: The presence of BMs was 34% overall, and when stratified by IMDC
      risk groups was 27%, 33%, and 43% in the favorable-, intermediate-, and poor-risk
      groups, respectively (p<0.001). The presence of LMs was 19% overall and higher in
      the poor-risk patients (23%) compared with the favorable- or intermediate-risk
      groups (17%) (p=0.003). When patients were classified into four groups based on
      the presence of BMs and/or LMs, the hazard ratio, adjusted for IMDC risk factors,
      was 1.4 (95% confidence interval [CI], 1.22-1.62) for BMs, 1.42 (95% CI, 1.17
      1.73) for LMs, and 1.82 (95% CI, 1.47-2.26) for both BMs and LMs compared with
      other metastatic sites (p<0.0001). The prediction model performance for OS was
      significantly improved when BMs and LMs were added to the IMDC prognostic model
      (likelihood ratio test p<0.0001). Data in this analysis were collected
      retrospectively. CONCLUSIONS: The presence of BMs and LMs in patients treated
      with targeted agents has a negative impact on survival. Patients with BMs and/or
      LMs may benefit from earlier inclusion on clinical trials of novel agents or
      combination-based therapies.

PMID- 23962748
TI  - Intestinal ischaemia as a severe presentation of Kawasaki disease leading to
      short-bowel syndrome.
AB  - The authors describe a case of Kawasaki disease who presented fever, coronary
      artery aneurysm, and ischaemic intestinal obstruction requiring stage resections.
      A review of literature of such association is performed. Atypical Kawasaki
      disease is more complex to diagnose and in combination of persistent fever with
      no definite cause and surgical abdominal pain, Kawasaki disease should be
      considered in the differential diagnosis. 

PMID- 23962747
TI  - Mediterranean diet and prostate cancer risk and mortality in the Health
      Professionals Follow-up Study.
AB  - BACKGROUND: Prostate cancer (PCa) mortality rates are lower in the Mediterranean
      countries compared with northern Europe. Although specific components of the
      Mediterranean diet (Med-Diet) may influence PCa risk, few studies have assessed
      the traditional Med-Diet pattern with the risk of incident advanced or lethal PCa
      or with disease progression among men diagnosed with nonmetastatic PCa.
      OBJECTIVE: To determine whether the traditional Med-Diet pattern is associated
      with risk of incident advanced or lethal PCa and with PCa-specific and overall
      mortality among men with PCa. DESIGN, SETTING, AND PARTICIPANTS: We prospectively
      followed 47 867 men in the Health Professionals Follow-up Study followed from
      1986 to 2010. The case-only analysis included 4538 men diagnosed with
      nonmetastatic PCa, followed from diagnosis to lethal outcome or to January 2010.
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used Cox proportional hazards
      models to examine traditional and alternative Med-Diet scores in relation to PCa
      incidence outcomes (advanced and lethal disease). In a case-only survival
      analysis, we examined postdiagnostic Med-Diet and risk of lethal (metastases or
      PCa death) and fatal PCa as well as overall mortality among men diagnosed with
      nonmetastatic disease. RESULTS AND LIMITATIONS: Between 1986 and 2010, 6220 PCa
      cases were confirmed. The Med-Diet was not associated with risk of advanced or
      lethal PCa. In the case-only analysis, there was no association between the Med
      Diet after diagnosis and risk of lethal or fatal PCa. However, there was a 22%
      lower risk of overall mortality (hazard ratio: 0.78; 95% confidence interval,
      0.67-0.90; p(trend)=0.0007) among men with greater adherence to the Med-Diet
      after PCa diagnosis. We found similar associations for the alternative score.
      CONCLUSIONS: A higher Med-Diet score was not associated with risk of advanced PCa
      or disease progression. Greater adherence to the Med-Diet after diagnosis of
      nonmetastatic PCa was associated with lower overall mortality.

PMID- 23962749
TI  - Hypoxia-enhanced derivation of iPSCs from human dental pulp cells.
AB  - Hypoxia enhances the reprogramming efficiency of human dermal fibroblasts to
      become induced pluripotent stem cells (iPSCs). Because we showed previously that
      hypoxia facilitates the isolation and maintenance of human dental pulp cells
      (DPCs), we examined here whether it promotes the reprogramming of DPCs to become
      iPSCs. Unlike dermal fibroblasts, early and transient hypoxia (3% O2) induced the
      transition of DPCs to iPSCs by 3.3- to 5.1-fold compared with normoxia (21% O2).
      The resulting iPSCs closely resembled embryonic stem cells as well as iPSCs
      generated in normoxia, as judged by morphology and expression of stem cell
      markers. However, sustained hypoxia strongly inhibited the appearance of iPSC
      colonies and altered their morphology, and anti-oxidants failed to suppress this
      effect. Transient hypoxia increased the expression levels of NANOG and CDH1 and
      modulated the expression of numerous genes, including those encoding chemokines
      and their receptors. Therefore, we conclude that hypoxia, when optimized for cell
      type, is a simple and useful tool to enhance the reprogramming of somatic cells
      to become iPSCs. 

PMID- 23962750
TI  - Construction, characterization and immunogenicity of a glycoprotein E negative
      bovine herpesvirus-1.1 Egyptian strain "Abu-Hammad".
AB  - A full glycoprotein E (gE) deletion was generated in genome of the Egyptian BoHV
      1.1 Abu-Hammad strain. Integrity of the gE negative (gE(-)) mutant virus was
      proved by successful specific PCR amplifications of gB, gC, tk, gD, gI and gE
      genes along with definite immune reaction to polyclonal anti-BoHV-1 antibody in
      infected cell culture. BoHV-1 gE(-) mutant exhibited growth kinetics inferior to
      those of the parental virus manifested as lower virus titers with delayed and
      poorer cytopathic effect in infected cells. Adjuvanted vaccines were made of the
      gE(-) mutant, live and killed; besides a conventional killed vaccine made of the
      parental virus and were used to immunize separate groups of calves. After i.m.
      vaccinations, no virus shedding could be detected in nasal swabs collected from
      all vaccinates and all calves remained apparently healthy. They all seroconverted
      to BoHV-1 as was revealed by virus neutralization test and a gB enzyme-linked
      immunosorbent assay (ELISA). Calves vaccinated with live and killed gE(-)
      vaccines did not elicit any detectable anti-gE antibody as shown by a blocking gE
      ELISA. In conclusion, the constructed BoHV-1.1 gE(-) mutant was proved as safe
      and immunogenic as a reliable candidate for inclusion in a local marker vaccine. 

PMID- 23962752
TI  - Interleukin-1 beta is an irradiation-induced stromal growth factor.
AB  - Gamma irradiation of tissues and organs leads to many pathological consequences
      due to the formation of reactive oxygen species, DNA damage and the subsequent
      massive death of cells. The therapeutic use of gamma irradiation in the treatment
      of cancer is based on its penetrating power and damaging effects on tumor cells.
      Other effects from the irradiation are unnoticeable in comparison. Moreover, the
      long-term consequences of gamma irradiation are still poorly understood. When a
      donor bone marrow plug is implanted under the renal capsule of a syngeneic
      animal, a hematopoietic ectopic focus is formed. The size of the focus is
      increased in mice that received irradiation compared to non-irradiated ones,
      regardless of the amount of time between irradiation and bone marrow plug
      implantation. Long-term repetitive injections of blood serum from irradiated mice
      given to syngeneic non-irradiated recipients of bone marrow plugs also lead to
      the formation of enlarged foci. Hence, the blood of irradiated animals must
      contain an activity that induces the growth of a hematopoietic microenvironment.
      It was previously shown that the bones of irradiated animals secrete a growth
      factor required to create stromal microenvironments. The identity of this factor
      has, until now, been difficult to obtain. We demonstrated that interleukin 1 beta
      (IL-1) stimulates the growth of murine bone marrow stromal cells in vitro and in
      vivo. It was shown that the expression of the Il1b gene and the secretion of its
      product, IL-1, were activated in bone cells long after total body gamma
      irradiation. Hence, IL-1, or proteins regulated by this cytokine, appears to be
      the same stromal growth factor previously observed in the serum of irradiated
      animals. Our data demonstrate several non-canonical functions of IL-1. In
      addition, the presence of up-regulated levels of IL-1 long after irradiation
      points to an unknown mechanism governing its gene expression.

PMID- 23962753
TI  - Oncology scan--low-grade gliomas: predicting and changing outcome.

PMID- 23962751
TI  - The Drosophila T-box transcription factor Midline functions within the Notch
      Delta signaling pathway to specify sensory organ precursor cell fates and
      regulates cell survival within the eye imaginal disc.
AB  - We report that the T-box transcription factor Midline (Mid), an evolutionary
      conserved homolog of the vertebrate Tbx20 protein, functions within the Notch
      Delta signaling pathway essential for specifying the fates of sensory organ
      precursor (SOP) cells. These findings complement an established history of
      research showing that Mid regulates the cell-fate specification of diverse cell
      types within the developing heart, epidermis and central nervous system. Tbx20
      has been detected in unique neuronal and epithelial cells of embryonic eye
      tissues in both mice and humans. However, the mechanisms by which either Mid or
      Tbx20 function to regulate cell-fate specification or other critical aspects of
      eye development including cell survival have not yet been elucidated. We have
      also gathered preliminary evidence suggesting that Mid may play an indirect, but
      vital role in selecting SOP cells within the third-instar larval eye disc by
      regulating the expression of the proneural gene atonal. During subsequent pupal
      stages, Mid specifies SOP cell fates as a member of the Notch-Delta signaling
      hierarchy and is essential for maintaining cell viability by inhibiting apoptotic
      pathways. We present several new hypotheses that seek to understand the role of
      Mid in regulating developmental processes downstream of the Notch receptor that
      are critical for specifying unique cell fates, patterning the adult eye and
      maintaining cellular homeostasis during eye disc morphogenesis. 

PMID- 23962754
TI  - The association between non-motor symptoms in Parkinson's disease and age at
      onset.
AB  - OBJECTIVE: Age at onset is likely to be related to a wide range of problems in
      Parkinson's disease (PD), including cardinal motor features, motor complications
      and non-motor symptoms (NMS). This study investigated the effect of the age at
      onset on NMS. METHODS: Two hundred and thirty patients were examined and
      classified into one of three groups based on age at onset: early onset PD (EOPD)
      group (<45 years), middle-age onset group (45-64 years) and old-age onset group
      (>=65 years). The trends relating to NMS were compared across the three groups.
      The EOPD and old-age onset groups were separately studied to determine their
      association to the appearance of non-motor features using logistic regression
      analysis. RESULTS: There were upward trends in the occurrence of dribbling
      (P=0.009; all P values are stated for trend), impaired taste/smelling (P=0.016),
      constipation (P=0.006), urinary urgency (P=0.002), nocturia (P=0.018),
      hallucinations (P=0.016) and acting out during dreams (P=0.011) with the increase
      of age at onset. Older age at onset is an independent risk factor for dementia
      (OR=8.42, CI 3.16-22.44), dribbling (OR=4.14, CI 1.93-8.87), impaired
      taste/smelling (OR=2.23, CI 1.20-4.13), constipation (OR=3.42, CI 1.88-6.24),
      incomplete bowel emptying (OR=2.23, CI 1.19-4.20), urinary urgency (OR=2.58 CI
      1.46-4.57), nocturia (OR=2.65, CI 1.49-4.71), hallucinations (OR=5.32, CI 1.78
      15.97), dizziness (OR=3.03, CI 1.59-5.79), falling (OR=3.60, CI 1.67-7.77),
      insomnia (OR=2.29, CI 1.28-4.11), intense vivid dreaming (OR=2.10, CI 1.21-3.66)
      and acting out during dreams (OR=2.23, CI 1.24-4.01). CONCLUSIONS: PD patients
      with different ages at onset present clinically different symptoms in terms of
      NMS. Old-age onset PD is characterized by more olfactory and sensory symptoms,
      autonomic symptoms, sleep disorders, dementia and psychosis compared to EOPD.

PMID- 23962755
TI  - Lipomas of the cerebellopontine angle: neuroradiological and surgical
      considerations. Review of the literature and report of our experience.

PMID- 23962756
TI  - Prediction of outcomes for brainstem cavernous malformation.
AB  - OBJECTIVE: Brainstem cavernous malformation (CM) poses a challenge to
      neurosurgeons in terms of operability, postoperative complications and
      unpredictable outcomes. The present study was conducted to analyze the clinical
      parameters that might predict the outcomes and to summarize our center experience
      in treatment of brainstem CM. METHODS: A total 59 patients with radiological and
      histologically confirmed brainstem CM diagnosed between 2000 and 2012 were
      retrospectively reviewed. All but five patients were deemed amenable to surgical
      resection. Complete resection was attempted in all CM and was achieved in 58/59
      patients. Modified Rankin scale (mRS) score dichotomized as mRS 0-2 (favorable
      outcome) or mRS 3-6 (unfavorable outcome) was employed for neurological status
      assessment. The association of various clinical parameters to the different
      brainstem location was evaluated. Predictors of the surgical outcomes were
      analyzed using the univariate and multivaraite regression statistics. RESULTS:
      Mean age of 32 female and 27 male patients was 34.3 years. The differences in
      size of cavernoma, conservative treatment and complications were significantly
      associated with various location of the CM in the brainstem. Clinical parameters
      including age at presentation (p=0.029, OR=0.061, CI=0.009-0.414), favorable
      preoperative mRS (p=0.004, OR=0.058, CI=0.009-0.343), pontine location of CM
      (p=0.018, OR=0.017, CI=0.001-0.495), and early surgical treatment (p=0.05,
      OR=0.087, CI=0.07-1.03) were independent predictors of favorable surgical
      outcomes. Mean long-term follow up of 42.9 months was available in 31/59 (52.5%).
      The mean size of CM was 22.5 mm; small size (<10 mm) at presentation was
      associated with favorable outcomes at long-term follow-up (univariate analysis,
      p=0.041, adjusted R2=0.471). Preoperative mRS (p=0.039) and location of the CM
      (p=0.034) in the brainstem were predictors of good surgical outcomes at long term
      follow-up. CONCLUSION: Favorable surgical outcomes can be predicted in brainstem
      CM patients with early age at presentation, pontine location of the cavernoma,
      favorable preoperative mRS and those undergoing early surgery. The outcomes at
      long-term follow-up were associated with location of the CM in the brainstem,
      size of the CM and the preoperative mRS.

PMID- 23962757
TI  - A deeply seated brain metastasis from a primary myxofibrosarcoma: case report.

PMID- 23962758
TI  - Glioependymal cyst in children: a case report.

PMID- 23962759
TI  - Childhood giant pituicytoma: a report and review of the literature.
AB  - OBJECTIVE: Pituicytoma is a rare, benign, primary tumour, almost all of which
      occur in adults. Here, we present one case of giant pituicytoma in a boy and a
      review literature to assist in understanding its natural history, behaviour,
      clinicopathological features and treatment options. METHODS: A PUBMED search
      using the keywords "pituicytoma" was performed, and the citations were reviewed.
      RESULTS: We found 65 cases of pituicytomas, including our report, in the
      international literature to date; among these cases, only three were diagnosed in
      patients under 14 years old. CONCLUSION: Pituicytoma is a slow-growing, rare, low
      grade glial neoplasm that originates in the neurohypophysis. Currently, the
      optimal treatment is gross total resection, and confirmed diagnosis relies upon
      pathological tests. Regular MRI follow-up is recommended.

PMID- 23962760
TI  - Steam and air co-injection in removing residual TCE in unsaturated layered sandy
      porous media.
AB  - Steam and air co-injection is a promising technique for volatile and semi
      volatile organic contaminant remediation in heterogeneous porous media. In this
      study, removal of trichloroethene (TCE) with steam-air co-injection was
      investigated through a series of 2D sandbox experiments with different layered
      sand structures, and through numerical simulations. The results show that a
      layered structure with coarse sand, in which steam and air convection are
      relatively rapid, resulted in a higher removal rate and a larger removal ratio
      than those observed in an experiment using finer sand; however, the difference
      was not significant, and the removal ratios from three experiments ranged from
      85% to 94%. Slight downward movement of TCE was observed for Experiment 1 (TCE
      initially in a fine sand zone encased in a coarse sand), while no such movement
      was observed for Experiment 2 (TCE initially in two fine sand layers encased in a
      coarse sand) or 3 (TCE initially in a silty sand zone encased in a coarse sand).
      Simulations show accumulation of TCE at the interface of the layered sands, which
      indicates a capillary barrier effect in restraining the downward movement of TCE.
      This effect is illustrated further by a numerical experiment with homogeneous
      coarse sand, in which continuous downward TCE movement to the bottom of the
      sandbox was simulated. Another numerical experiment with higher water saturation
      was also conducted. The results illustrate a complicated influence of water
      saturation on TCE removal in a layered sand structure. 

PMID- 23962761
TI  - Acyl glycosides with rare beta-D-apiofuranosyl-beta-D-glucopyranosyl-beta-D
      apiofuranosyl from Erycibe hainanesis.
AB  - Three new acyl glycosides with rare beta-D-apiofuranosyl-(1->2)-[beta-D
      apiofuranosyl-(1->6)]-beta-D-glucopyranosyl moieties, 2-O-[2,6-O-bis(5-O
      syringoyl-beta-D-apiofuranosyl)-beta-D-glucopyranosyl]-isopropyl alcohol (1), 1-O
      [2,6-O-bis(5-O-syringoyl-beta-D-apiofuranosyl)-beta-D-glucopyranosyl]-isoamyl
      alcohol (2), and 1-O-[2,6-O-bis(5-O-vanilloyl-beta-D-apiofuranosyl)-beta-D
      glucopyranosyl]-3,4,5-trimethoxyphenol (3) were obtained from Erycibe hainanesis.
      Their structures were determined by UV, IR, HRESIMS, (1)D and (2)D NMR data, and
      by chemical methods. Compounds 1-3 were evaluated against D-galactosamine induced
      toxicity in WB-F344 rat hepatic epithelial stem-like cells, and compounds 1 and 3
      showed moderate hepatoprotective activities.

PMID- 23962762
TI  - The depolymerized fucosylated chondroitin sulfate from sea cucumber potently
      inhibits HIV replication via interfering with virus entry.
AB  - Fucosylated chondroitin sulfate (FuCS-1) is a nontoxic and water-soluble
      depolymerized glycosaminoglycan obtained from the sea cucumber Thelenota ananas.
      Anti-HIV activities of FuCS-1 were evaluated in the present study. FuCS-1 was
      effective in blocking laboratory strain HIV-1IIIB entry and replication
      (4.26MUg/mL and 0.73MUg/mL, respectively), and inhibiting infection by clinic
      isolate HIV-1KM018 and HIV-1TC-2 (23.75MUg/mL and 31.86MUg/mL, respectively) as
      well as suppressing HIV-1 drug-resistant virus. It also inhibited HIV-2ROD and
      HIV-2CBL-20 replication (100MUg/mL). Notably, FuCS-1 showed highly effective
      antiviral activity against T-20-resistant strains (EC50 values ranging from
      0.76MUg/mL to 1.13MUg/mL). Further studies indicated that FuCS-1 can potently
      bind the recombinant HIV-1 gp120 protein, but no inhibition of recombinant HIV-1
      reverse transcriptase was observed. In conclusion, FuCS-1 inhibited several
      strains of HIV-1 replication with different potencies. These results suggest that
      FuCS-1 may possess great potential to be further developed as novel HIV-1 entry
      inhibitor for treatment of HIV/AIDS patients, particularly for those infected by
      T-20-resistant variants. 

PMID- 23962763
TI  - A Taenia crassiceps metacestode factor enhances ovarian follicle atresia and
      oocyte degeneration in female mice.
AB  - The histopathological effects of Taenia crassiceps infection or T. crassiceps
      metacestode factor inoculation on the mouse ovary were determined using six
      female mice in three groups: infected mice, mice inoculated with the metacestode
      factor and control mice. The control group was subcutaneously inoculated with
      healthy peritoneal fluid. The infected group was intraperitoneally inoculated
      with 40 T. crassiceps metacestodes, and the metacestode factor group was
      subcutaneously inoculated with T. crassiceps metacestode factor (MF). Light and
      electron microscopy and TUNEL (terminal deoxynucleotidyl transferase (TdT)
      mediated dUTP nick end labelling) assays revealed a significant increase in
      ovarian follicular atresia (predominantly in antral/preovulatory stages of
      development), oocyte degeneration (P< 0.05), and a decrease in the amount of
      corpus luteum in follicles of mice infected and inoculated with MF compared with
      the control group. Significant abnormalities of the granulosa cells and oocytes
      of the primordial, primary and secondary ovarian follicles occurred in both
      treated mouse groups (P< 0.05) compared with no degeneration in the control
      group. These pathological changes in female mice either infected with T.
      crassiceps metacestodes or inoculated with T. crassiceps MF may have consequences
      for ovulation and fertility. 

PMID- 23962764
TI  - Foreign body aspiration in children: experience from 2624 patients.
AB  - OBJECTIVES: The objective of this study is to analyze the epidemiological,
      clinical, radiological and endoscopic characteristics of pediatric foreign body
      aspiration in Algeria. METHODS: In this retrospective study, the results of 2624
      children younger than 18 years admitted in our department for respiratory foreign
      body removal between 1989 and 2012, were presented. Most of them had an
      ambulatory rigid bronchoscopy. RESULTS: The children (62.34% males and 37.65%
      females) were aged 4 months to 18 years with 66% between 1 and 3 years. Choking
      was related in 65% of cases. The delay between aspiration and removal was 2-8
      days in 65.8% and within 24 h in 9.2%. In the most cases, the children arrived
      with cough, laryngeal or bronchial signs and unilateral reduction of vesicular
      murmur. The examination was normal in 13%. The most common radiologic finding was
      pulmonary air trapping (40.7%). The aspirated bodies were organic in 66.7%,
      dominated by peanuts, while sunflower seeds, beans and ears of wheat were the
      most dangerous. In the other cases, they were metallic or plastic as pen caps and
      recently scarf pins. The endoscopic removal by rigid bronchoscopy was successful
      and complete in 97%. Cases with extraction failure (3%) limited to certain FBs,
      all of them inorganic were assigned to surgery. The complications related to the
      endoscopic procedure were 0.29% with a mortality of 0.26%. CONCLUSION: Foreign
      body aspiration is a real public health problem in Algeria. The best way to
      manage it is an early diagnosis and a rigid bronchoscopy removal under general
      anesthesia used by fully trained staff. The prevention of this domestic accident
      should consider the population lifestyle and cultural habits to be more
      effective.

PMID- 23962765
TI  - Logistic regression analysis of risk factors for prolonged pulmonary recovery in
      children from aspirated foreign body.
AB  - OBJECTIVE: Foreign body aspiration is a life-threatening emergency for children.
      Fried chicken is commonly available all over the world, but no cases have
      previously been reported addressing this food as a tracheobronchial foreign body.
      We report an extremely rare case of tracheobronchial aspiration of fried chicken
      complicated by severe bronchitis and postoperative atelectasis. To clarify
      predisposing factors related to bronchopulmonary complications, we also reviewed
      paediatric cases of tracheobronchial foreign bodies treated in our department
      over the past 14 years. METHODS: We retrospectively reviewed a total of 77 cases
      of tracheobronchial foreign bodies from 1988 to 2011. The main outcome measure
      was duration of hospitalisation, reflecting postoperative therapy. Logistic
      regression analyses were conducted to determine risk factors for longer
      hospitalisation. RESULTS: Age, sex, and interval between the aspiration episode
      and bronchoscopy were not significantly associated with longer hospitalisation.
      Regarding kinds of foreign bodies, higher rates of longer hospitalisation were
      noted for patients who had aspirated peanut or animal material, as compared to
      patients who had aspirated non-organic material (odds ratio, 5.80; 95% confidence
      interval, 1.12-30.43). CONCLUSIONS: In terms of predicting the risk of pulmonary
      complications, the type of foreign body aspirated offers a more meaningful factor
      than the interval between aspiration and operation. Specifically, peanuts or
      animal material containing oils appear to be associated with a more prolonged
      pulmonary recovery even after retrieval of the foreign body.

PMID- 23962766
TI  - Modality-specific occult intrarenal pseudoaneurysm in a renal allograft and the
      legacy of catheter angiography.
AB  - A 69-year-old man with history of end-stage-renal disease (ESRD) underwent
      successful kidney transplantation from a cadaveric donor in November 2011.
      However, posttransplant recovery was complicated by delayed graft function and
      recurrent gross hematuria. Serial Doppler ultrasound (US) of the renal allograft
      demonstrated a pseudoaneurysm with interval increase in size. However, it could
      not be visualized with other modalities, including an initial angiogram
      (postoperative day 49) and a second angiogram (postoperative day 68), followed by
      surgical exploration (postoperative day 71), which demonstrated complete intra
      aneurysmal thrombosis on intraoperative Doppler US. Unfortunately, the patient's
      hematuria continued and a repeat Doppler US 48 hours later demonstrated a
      persistent pseudoaneurysm. Therefore, on postoperative day 75, we performed
      targeted percutaneous intra-aneurysmal thrombin injection under dual image
      guidance, which showed complete intra-aneurysmal thrombosis on intraprocedural
      Doppler US. Hematuria recurred the next day. A third angiogram (postoperative day
      77) finally illuminated the hidden pseudoaneurysm occult on the first and second
      angiographic studies (sensitivity [index case] 33%) and surgery. This allowed for
      successful coil embolization of a subsegmental feeding branch with an excellent
      outcome. We support a more aggressive management with serial angiography and
      embolization of the intrarenal symptomatic pseudoaneurysm rather than surgery in
      renal allograft recipients, with the benefits outweighing the risks. 

PMID- 23962767
TI  - Distribution of normal superficial ocular vessels in digital images.
AB  - PURPOSE: To investigate the distribution of different-sized vessels in the
      digital images of the ocular surface, an endeavor which may provide useful
      information for future studies. METHODS: This study included 295 healthy
      individuals. From each participant, four digital photographs of the superior and
      inferior conjunctivae of both eyes, with a fixed succession of photography (right
      upper, right lower, left upper, left lower), were taken with a slit lamp mounted
      camera. Photographs were then analyzed by a previously described algorithm for
      vessel detection in the digital images. The area (of the image) occupied by
      vessels (AOV) of different sizes was measured. Height, weight, fasting blood
      sugar (FBS) and hemoglobin levels were also measured and the relationship between
      these parameters and the AOV was investigated. RESULTS: These findings indicated
      a statistically significant difference in the distribution of the AOV among the
      four conjunctival areas. No significant correlations were noted between the AOV
      of each conjunctival area and the different demographic and biometric factors.
      Medium-sized vessels were the most abundant vessels in the photographs of the
      four investigated conjunctival areas. The AOV of the different sizes of vessels
      follows a normal distribution curve in the four areas of the conjunctiva. The
      distribution of the vessels in successive photographs changes in a specific
      manner, with the mean AOV becoming larger as the photos were taken from the right
      upper to the left lower area. CONCLUSIONS: The AOV of vessel sizes has a normal
      distribution curve and medium-sized vessels occupy the largest area of the
      photograph.

PMID- 23962768
TI  - A simplified technique to determine random coincidence summing of gamma rays and
      dead time count loss corrections.
AB  - The loss in counts rate under the peak in gamma spectrum was studied using two
      techniques (complex spectrum and high active single isotope). The results showed
      that the loss was occurred when the integrated counting rate was more than 400
      counts per second (CPS) up to 10(4)cps, for energy range 20-2,500 keV. This was
      mainly due to the random summing effect in the detector's volume. It was found
      that the probability of random summing has increased with the increase of the
      volume of detector's crystal. The correction factor F(Ct) for the counts rate
      under the peak was determined experimentally.

PMID- 23962769
TI  - Prehospital high-dose sublingual nitroglycerin rarely causes hypotension.
AB  - INTRODUCTION: High-dose intravenous nitroglycerin is a common in-hospital
      treatment for respiratory distress due to congestive heart failure (CHF) with
      hypertension. Intravenous (IV) nitroglycerin administration is impractical in the
      prehospital setting. In 2011, a new regional Emergency Medical Services (EMS)
      protocol was introduced allowing advanced providers to treat CHF with high-dose
      oral nitroglycerin. The protocol calls for patients to be treated with two
      sublingual tabs (0.8 mg) when systolic blood pressure (SBP) was >160 mm Hg, or
      three sublingual tabs (1.2 mg) when SBP was >200 mm Hg, every five minutes as
      needed. Hypothesis/Problem To assess the protocol's safety, the incidence of
      hypotension following prehospital administration of multiple simultaneous
      nitroglycerin (MSN) tabs by EMS providers was studied. METHODS: This study was a
      retrospective cohort study of patients from a single commercial EMS agency over a
      6-month period. Records from patients with at least one administration of MSN
      were reviewed. For each administration, the first documented vital signs pre- and
      post-administration were compared. Administrations were excluded if pre- or post
      administration vital signs were missing. RESULTS: One hundred case-patients had
      at least one MSN administration by an advanced provider during the study period.
      Twenty-five case-patients were excluded due to incomplete vital signs. Seventy
      five case-patients with 95 individual MSN administrations were included for
      analysis. There were 65 administrations of two tabs, 29 administrations of three
      tabs, and one administration of four tabs. The mean change in SBP following MSN
      was -14.7 mm Hg (SD = 30.7; range, +59 to -132). Three administrations had
      documented systolic hypotension in the post-administration vital signs (97/71,
      78/50 and 66/47). All three patients were over 65 years old, were administered
      two tabs, had documented improved respiratory status, and had repeat SBP of at
      least 100. The incidence of hypotension following MSN administration was 3.2%.
      Discussion High-dose oral nitroglycerin administration is a practical alternative
      to IV nitroglycerin in the prehospital setting when administered by advanced
      providers. The prehospital protocol for high dose oral nitroglycerin was
      demonstrated to be safe in the cohort of patients studied. Limitations of the
      study include the relatively small sample size and the inability to identify
      hypotension that may have occurred following the cessation of data collection in
      the field. CONCLUSION: Hypotension was rare and self-limited in prehospital
      patients receiving MSN.

PMID- 23962770
TI  - Sequential analysis of mothers' and fathers' reassurance and children's
      postoperative distress.
AB  - OBJECTIVE: Children experience distress after surgery. Associations exist between
      parent reassurance (e.g., "It's OK") and child distress, but little is known
      about the causal direction of these interactions. This study examined sequential
      relations between mothers' and fathers' reassurance and children's distress.
      METHODS: 146 families with 2- to 11-year-olds undergoing elective surgery
      participated. Time-event coding and time-window sequential analysis examined
      whether reassurance preceded or followed child distress. Secondary analyses
      examined the relation of child sex and parent anxiety with the
      reassurance/distress contingency. RESULTS: Reassurance was positively correlated
      with distress; however, nonverbal distress was less likely to start following
      reassurance and was also more likely to continue following reassurance. Mothers
      were more likely to reassure following boys' verbal distress, and mothers with
      higher anxiety were more likely to reassure following nonverbal distress.
      CONCLUSIONS: Whereas parental reassurance may prevent the start of child
      distress, it might maintain ongoing child distress.

PMID- 23962771
TI  - Noninvasive delivery of siRNA and plasmid DNA into skin by fractional ablation:
      erbium:YAG laser versus CO2 laser.
AB  - The present study was conducted to evaluate the impacts of fractional erbium
      (Er):YAG and CO2 lasers on skin permeation of small interfering (si)RNA and
      plasmid (p)DNA vectors. In vitro skin delivery was determined with a Franz
      diffusion cell. In vivo absorption was investigated by observing fluorescence and
      confocal microscopic imaging. Fractional laser-mediated ablation of the skin
      resulted in significant enhancement of dextran and siRNA penetration. Respective
      fluxes of dextran (10 kDa) and siRNA, which had similar molecular size, with
      Er:YAG laser irradiation at 5 J/cm(2) were 56- and 11-fold superior to that of
      intact skin. The respective permeation extents of dextran and siRNA by the CO2
      laser at 4 mJ/400 spots were 42- and 12-fold greater than that of untreated skin.
      Fluorescence and confocal images showed increased fluorescence intensities and
      penetration depths of siRNA and pDNA delivery. According to an examination of the
      follicular permeant amount and fluorescence microscopy, hair follicles were
      important deposition areas for fractional laser-assisted delivery, with the
      Er:YAG modality revealing higher follicular siRNA selectivity than the CO2
      modality. This is the first report of siRNA and pDNA penetrating the skin with a
      sufficient amount and depth with the assistance of fractional lasers.

PMID- 23962773
TI  - Recognition of International Board Certified Lactation Consultants by health
      insurance providers in the United States: results of a national survey of
      lactation consultants.
AB  - BACKGROUND: Insurance coverage for lactation management is proposed by the United
      States Affordable Care Act. International Board Certified Lactation Consultants
      (IBCLCs) are key providers of lactation services. In order to inform national
      discussion, this study examines the scope of insurance reimbursement of IBCLC
      services. OBJECTIVES: An email survey of US IBCLCs (N = 10 495) in March 2011 was
      used to explore frequencies of (1) submission--how often lactation consults were
      submitted to insurance providers for reimbursement and (2) recognition--the
      proportion of submitted charges recognized by insurance providers. METHODS:
      Results (N = 2045) were analyzed to describe patterns of submission and
      recognition by IBCLC work setting, job classification, and reimbursement
      strategy. RESULTS: Many survey respondents did not know their submission (41%) or
      recognition (57%) levels. Multiple strategies were used for reimbursement of
      IBCLC services with large variations in recognition between strategies. Overall,
      less than 15% reported high levels of submissions to insurance providers.
      Moreover, of submitted encounters, only 4% were consistently recognized by
      insurance providers. Inpatient hospital IBCLCs were least likely to have consults
      recognized (3%), and private community IBCLCs were most frequently recognized
      (32%). Compared with using IBCLC credentials for submitting an encounter, using
      another clinical license was the most successful strategy for achieving
      recognition of IBCLC consults (crude risk ratio, 1.44; 95% confidence interval,
      1.04-2.01; P = .02). CONCLUSION: IBCLCs provide key care to a vulnerable
      population. However, we found that these services are not consistently
      reimbursed. IBCLCs poorly communicate their health care activities to insurance
      providers, but insurance providers also inconsistently recognize and reimburse
      IBCLC care.

PMID- 23962772
TI  - Therapeutic effect of Artemia enriched with Escherichia coli expressing double
      stranded RNA in the black tiger shrimp Penaeus monodon.
AB  - We exploited Artemia as a double-stranded (ds)RNA-delivery system to combat viral
      diseases in shrimp. First, the transformed Escherichia coli (E. coli) expressing
      red fluorescent protein (RFP) was tested in the Artemia enrichment process. RFP
      signals detectable in the gut of Artemia under confocal microscope were evident
      for the successful encapsulation. Second, the Artemia enrichment process was
      performed using E. coli producing Laem-Singh virus (LSNV)-specific dsRNA, which
      has been previously shown to inhibit the viral infection in the black tiger
      shrimp Penaeus monodon by intramuscular injection and oral administration. The
      enriched Artemia nauplii were confirmed to contain dsRNA-LSNV by RT-PCR, and were
      subjected to the feeding test with P. monodon postlarvae. Quantitative RT-PCR
      indicated that a number of LSNV copies in most of the treated shrimp were, at
      least, 1000-fold lower than the untreated controls. During 11-17weeks after
      feeding, average body weight of the treated group was markedly increased relative
      to the control group. A smaller differential growth rate of the treated group as
      compared to the control was also noticed. These results suggested that feeding
      shrimp with the dsRNA-enriched Artemia can eliminate LSNV infection, which is the
      cause of retarded growth in P. monodon. The present study reveals for the first
      time the therapeutic effect of dsRNA-enriched Artemia for shrimp disease control.

PMID- 23962774
TI  - Changes in all-cause and cardiovascular disease mortality in three different
      Finnish population cohorts with and without diabetes.
AB  - BACKGROUND: We aimed to assess changes in cardiovascular (CVD) and all-cause
      mortality among diabetic and non-diabetic individuals between three large study
      cohorts with baseline assessments of 10 years apart and followed up for 10 years.
      METHODS: Six population surveys were carried out in 1972, 1977, 1982, 1987, 1992
      and 1997 in Finland. For the analyses we combined the 1972 and 1977 cohorts
      (cohort 1), the 1982 and 1987 cohorts (cohort 2) and similarly also the 1992 and
      1997 cohorts (cohort 3). RESULTS: Age-adjusted hazard ratio (HR) of all-cause
      mortality and CVD in men without diabetes showed that both had a statistically
      significant decreased risk of all-cause mortality compared to the first cohort.
      No statistically significant changes in all-cause mortality were observed in men
      and women with diabetes between the latter two cohorts compared with the first
      after controlling for several covariates. In both men and women without diabetes,
      cohort 2 (men, HR=0.65; 95% CI 0.51-0.82; women, HR=0.54; 95% CI 0.32-0.89) and
      cohort 3 (men, HR=0.32; 95% CI 0.22-0.47; women, HR=0.31; 95% CI 0.14-0.68)
      showed a statistically significant decreased risk of CVD mortality compared to
      cohort 1. Age-adjusted HRs in regard to CVD mortality in men (HR=0.22; 95% CI
      0.07-0.69) and women (HR=0.22; 95% CI 0.05-0.99) with diabetes of cohort 3 were
      statistically significantly lower than in cohort 1. CONCLUSIONS: There seems to
      be a decrease in CVD mortality in people with diabetes indicating that treatment
      of diabetes and cardiovascular risk factors in diabetes patients may have
      improved during the last decade.

PMID- 23962775
TI  - Physical activity is associated with improved aerobic exercise capacity over time
      in adults with congenital heart disease.
AB  - BACKGROUND: Impaired exercise capacity is common in adults with congenital heart
      disease (ACHD). This impairment is progressive and is associated with increased
      morbidity and mortality. We studied the influence of the frequency of at least
      moderately strenuous physical activity (PhysAct) on changes in exercise capacity
      of ACHD patients over time. METHODS: We studied ACHD patients >=21 years old who
      had repeated maximal (RER>=1.09) cardiopulmonary exercise tests within 6 to 24
      months. On the basis of data extracted from each patient's clinical records,
      PhysAct frequency was classified as (1) Low: minimal PhysAct, (2) Occasional:
      moderate PhysAct <2 times/week, or (3) Frequent: moderate PhysAct >=2 times/week.
      RESULTS: PhysAct frequency could be classified for 146 patients. Those who
      participated in frequent exercise tended to have improved pVO2 (?pVO2=+1.63+/
      2.67 ml/kg/min) compared to those who had low or occasional activity frequency
      (?pVO2=+0.06+/-2.13 ml/kg/min, p=0.003) over a median follow-up of 13.2 months.
      This difference was independent of baseline clinical characteristics, time
      between tests, medication changes, or weight change. Those who engaged in
      frequent PhysAct were more likely to have an increase of pVO2 of >=1SD between
      tests as compared with sedentary patients (multivariable OR=7.4, 95%CI 1.5-35.7).
      Aerobic exercise capacity also increased for patients who increased activity
      frequency from baseline to follow-up; 27.3% of those who increased their
      frequency of moderately strenuous physical activity had a clinically significant
      (at least +1SD) increase in pVO2 compared to only 11% of those who maintained or
      decreased activity frequency. CONCLUSIONS: ACHD patients who engage in frequent
      physical activity tend to have improved exercise capacity over time.

PMID- 23962776
TI  - Contrasting circulating microbiome in cardiovascular disease patients and healthy
      individuals.

PMID- 23962777
TI  - HDL cholesterol in cardiovascular diseases: the good, the bad, and the ugly?
AB  - Atherosclerotic cardiovascular diseases are the leading cause of death in
      developed and developing countries. HDL-raising therapeutic modalities (such as
      cholesterol ester transferase protein (CETP) inhibitors) are being developed to
      combat these diseases. However, recent setback of two CETP inhibitors
      (Torcetrapib and Dalcetrapib) has highlighted the importance of measuring
      qualitative functionality of HDL particles, rather than focusing quantitatively
      on HDL cholesterol serum concentrations. It has been known that, HDL from
      patients with coronary artery disease (CAD) (i.e., HDL(CAD)) limits the anti
      inflammatory and endothelial repair properties of normal HDL, due to the
      activation of lectin-like oxidized LDL receptor-1 (LOX-1), thereby causing
      failure in endothelial nitric oxide (NO) production. A more recent study
      (Immunity 2013; 38: 754-768) also demonstrates that HDL from patients with
      chronic kidney dysfunction (CKD) (i.e., HDL(CKD)), unlike its healthy counterpart
      (i.e., HDL(Healthy)), promotes superoxide production, reduces NO bioavailability
      and raises blood pressure via toll-like receptor-2 (TLR-2) activation. This study
      provides novel insights into understanding why HDL-raising agents failed to
      demonstrate beneficial effects on cardiovascular mortality in large clinical
      trials and why CKD accelerates the development of atherosclerosis in CAD
      patients. Further research is warranted to elucidate whether HDL(CKD) and
      HDL(CAD) participate in other cellular processes in atherosclerosis, such as foam
      cell formation, the proliferation and migration of smooth muscle cells, and most
      importantly, plaque destabilization. 

PMID- 23962778
TI  - Estrogens protect myocardium against ischemia/reperfusion insult by up-regulation
      of CRH receptor type 2 in female rats.
AB  - BACKGROUND: The mechanism underlying estrogen cardioprotection remains largely
      unknown. Urocortin (UCN), a member of corticotropin-releasing hormone (CRH)
      family, is one of endogenous cardioprotective factors. The goal of present study
      is to investigate whether estrogens regulate UCN and its receptor CRH receptor
      type 2 (CRHR2) in female rat heart. METHODS: 17beta-estradiol (E2) was
      subcutaneously administrated to ovariectomized (OVX) rats for eight weeks. UCN
      was administrated before simulated myocardial ischemia/reperfusion (I/R). Cell
      damage was assessed by measurement of infarct size, activity of serum creatine
      kinase (CK) and lactate dehydrogenase (LDH) and percentage of TUNEL staining in
      myocardium. The mRNA and protein levels of UCN and CRHR2 were determined in sham
      operated and OVX rats with or without E2 replacement. DNA methylation frequency
      of CRHR2 gene promoter was determined by bisulfite-sequencing. RESULTS: UCN
      administration reduced infarct size, LDH and CK level and percentage of TUNEL
      staining upon I/R injury. The cardioprotective effects of UCN were abrogated in
      OVX rats and E2 replacement restored UCN-induced cardioprotection.CRHR2 mRNA and
      protein expression were down-regulated more than 40% in OVX rats, both of which
      were restored by E2 replacement. UCN mRNA and protein levels were not affected by
      ovariectomy and E2 replacement. Hypermethylation in CRHR2 promoter was found in
      OVX rats, and two of the methylated CpG sites were seated at cis-acting elements.
      Hypermethylation induced by OVX could also be ameliorated by E2 replacement.
      CONCLUSION: Estrogens maintain CRHR2 expression in myocardium, which may through
      an epigenetic mechanism, and enhance UCN-induced cardioprotective effects against
      I/R injury.

PMID- 23962779
TI  - Aneurysm associated with normal coronary arteries: a diagnostic dilemma.

PMID- 23962781
TI  - Severe heart failure prognosis evaluation for transplant selection in the era of
      beta-blockers: role of peak oxygen consumption.

PMID- 23962782
TI  - Tele-accelerometry as a novel technique for assessing functional status in
      patients with heart failure: feasibility, reliability and patient safety.
AB  - BACKGROUND: The six-minute walk test (6MWT) is an established measure of
      functional exercise capacity associated with clinical prognosis in Chronic Heart
      Failure (CHF). The aim of this study is to evaluate the employment of tele
      accelerometry for the remote assessment of 6MWT in CHF. METHODS: 155 patients
      were subjected to tele-accelerometry in form of monthly 6MWTs in their home
      surroundings. Accelerometer output included steps/6 min and walking speed. Data
      was directly transferred via mobile network to the Telemedicine Centre subsequent
      to test completion. 6MWT distance was measured by hand wheel and steps were
      counted with a digital hand-counter at baseline (Test 1) and at 12 months follow
      up (Test 2). RESULTS: Accelerometer accuracy was within the 99th percentile.
      There was a significant correlation between step count, walking speed and
      measured 6MWT distance (Test 1: steps: r=0.80, P<0.001; Test 2: steps: r=0.90,
      P<0.001 and Walking Speed Test 1: r=0.80, P<0.001; Walking Speed Test 2: r=0.86,
      P<0.001). The reproducibility of tele-accelerometry was within 95% margin for all
      performance parameters, which showed stronger associations to quality of life
      questionnaire (Short Form - 36) Physical Component Score (PCS) than New York
      Heart Association (NYHA) functional class. CONCLUSION: Tele-accelerometry is
      feasible in patients with CHF and output parameters are indicative of exercise
      capacity. The benefit of this approach lies in its simplicity under every day
      circumstances by enabling routine performance testing to assess patients'
      functional status.

PMID- 23962783
TI  - Natriuretic peptides and the Framingham risk score for screening of asymptomatic
      left ventricular systolic dysfunction in high-risk patients in primary care. The
      DAVID-BERG study.

PMID- 23962780
TI  - Relationship between systolic blood pressure and preserved or reduced ejection
      fraction at admission in patients hospitalized for acute heart failure syndromes.
AB  - BACKGROUND: Among patients with acute heart failure syndromes (AHFS), it has been
      reported that those with a reduced left ventricular ejection fraction (LVEF) tend
      to be hypotensive or normotensive, whereas those with a preserved LVEF tend to be
      hypertensive. However, it is unclear whether the systolic blood pressure (SBP) is
      actually associated with the LVEF in AHFS patients. Therefore, we evaluated the
      relationship between the SBP at admission and LVEF in patients hospitalized for
      AHFS. METHODS: Data from the Acute Decompensated Heart Failure Syndromes (ATTEND)
      registry were analyzed to investigate the relationship between the admission SBP
      and a preserved or reduced LEF in AHFS patients. Of the 4,842 patients enrolled
      in this registry, 4,831 patients (99.8%) were evaluated. They were divided into
      SBP quartiles (SBP <120, 120 to <140, 140 to <160, and >=160 mmHg), and LVEF was
      compared among the quartiles. RESULTS: Patients with an admission SBP <120 mmHg
      were more likely to have a reduced LVEF than a preserved LVEF. In contrast,
      patients with an admission SBP >=120 mmHg were equally likely to have a preserved
      or reduced LVEF, indicating that there was no relation between a higher admission
      SBP and the LVEF. CONCLUSIONS: Our data indicated that an elevated SBP at
      admission may not be useful to distinguish between a preserved or reduced LVEF in
      the urgent phase of AHFS. However, taking geographical differences of AHFS into
      consideration, further investigations are needed to clarify the relationship
      between admission SBP and LVEF in patients hospitalized for AHFS.

PMID- 23962784
TI  - Myosin light chain kinase inhibitor attenuates atherosclerosis and permeability
      via reduced endothelial tight junction in rabbits.

PMID- 23962785
TI  - Six-minute walk test distance and resting oxygen saturations but not functional
      class predict outcome in adult patients with Eisenmenger syndrome.
AB  - BACKGROUND: Eisenmenger syndrome (ES) represents the extreme manifestation of
      pulmonary arterial hypertension in patients with congenital heart disease,
      associated with significant exercise intolerance and mortality. Even though of
      six-minute-walk-test (6MWT) is routinely used in these patients, little is known
      about its prognostic value in comparison to functional class. METHODS AND
      RESULTS: We included 210 adult patients with ES who underwent a total of 822
      6MWTs. Median walking distance (6MWD) was 330 m [IQR 260-395], oxygen saturation
      (SO2) at baseline 86% [IQR 82-91%] and SO2 at peak-exercise 69% [IQR 60-80%]. In
      patients commenced on advanced therapy for pulmonary hypertension, but not in the
      reminder, there was a significant improvement in walking distance (297+/-97 m vs.
      325+/-87 m,P=0.0019), SO2 at rest (84.9+/-7.1 vs. 86.8+/-5.9%,P=0.003), SO2 at
      peak exercise (69.1+/-12.7 vs. 72.3+/-12.2%,P=0.04) and NYHA functional class
      (P=0.0047). During a follow up of 3.3 years, 29 patients died. On time-dependent
      Cox analysis, 6MWD (HR 0.94 per 10 m, 95%CI: 0.91-0.97,P<0.001) and baseline SO2
      (HR 0.90, 95%CI:0.86-0.94,P<0.0001) were predictors of death. In contrast, age,
      functional class, peak-exercise SO2 and SO2 change were not related to mortality.
      A three-fold increased risk of death was identified in patients not reaching a
      6MWD of 350 m or with baseline SO2 below 85%. CONCLUSIONS: The 6MWD and resting
      SO2, but not functional class were predictive of outcome in this contemporary
      cohort of Eisenmenger patients and should be incorporated in both risk
      stratification and management algorithms for these patients.

PMID- 23962786
TI  - High dose statins should be used in all patients undergoing percutaneous coronary
      intervention.

PMID- 23962787
TI  - Substance P acting via the neurokinin-1 receptor regulates adverse myocardial
      remodeling in a rat model of hypertension.
AB  - BACKGROUND: Substance P is a sensory nerve neuropeptide located near coronary
      vessels in the heart. Therefore, substance P may be one of the first mediators
      released in the heart in response to hypertension, and can contribute to adverse
      myocardial remodeling via interactions with the neurokinin-1 receptor. We asked:
      1) whether substance P promoted cardiac hypertrophy, including the expression of
      fetal genes known to be re-expressed during pathological hypertrophy; and 2) the
      extent to which substance P regulated collagen production and fibrosis. METHODS
      AND RESULTS: Spontaneously hypertensive rats (SHR) were treated with the
      neurokinin-1 receptor antagonist L732138 (5mg/kg/d) from 8 to 24 weeks of age.
      Age-matched WKY served as controls. The gene encoding substance P, TAC1, was up
      regulated as blood pressure increased in SHR. Fetal gene expression by
      cardiomyocytes was increased in SHR and was prevented by L732138. Cardiac
      fibrosis also occurred in the SHR and was prevented by L732138. Endothelin-1 was
      up-regulated in the SHR and this was prevented by L732138. In isolated cardiac
      fibroblasts, substance P transiently up-regulated several genes related to cell
      cell adhesion, cell-matrix adhesion, and extracellular matrix regulation,
      however, no changes in fibroblast function were observed. CONCLUSIONS: Substance
      P activation of the neurokinin-1 receptor induced expression of fetal genes
      related to pathological hypertrophy in the hypertensive heart. Additionally,
      activation of the neurokinin-1 receptor was critical to the development of
      cardiac fibrosis. Since no functional changes were induced in isolated cardiac
      fibroblasts by substance P, we conclude that substance P mediates fibrosis via up
      regulation of endothelin-1.

PMID- 23962789
TI  - Identification of clinically relevant HPV-related HNSCC: in p16 should we trust?

PMID- 23962788
TI  - Androgen receptor increases CD133 expression and progenitor-like population that
      associate with cisplatin resistance in endometrial cancer cell line.
AB  - Endometrial cancer (EMC) is a sex steroid hormone-related female malignancy.
      Androgen and androgen receptor (androgen/AR) signals have been implicated in EMC
      progression. Cancer stem/progenitor cells (CSPCs) are suspected to link to
      chemoresistance in patients with EMC. In this study, we examined the androgen/AR
      roles in cisplatin resistance and CSPC population. We found AR expression
      increased naive EMC side population, CSPC population, cell migration, and
      epithelial-mesenchymal transition. Meanwhile, it decreased cisplatin cytotoxic
      effect on EMC cells. Collaterally, endogenous AR expressions in EMC cells were
      upregulated in the cisplatin-resisting state. Moreover, AR expression could
      further enhance CD133 expression, CSPC-related markers, and drug-resistance gene
      messenger RNA expression in EMC cells. Finally, the AR-associated gene expression
      might go through indirect regulation. This is the first report revealing AR
      function on EMC cells' CSPC and cisplatin resistance. 

PMID- 23962790
TI  - Transforming growth factor-beta and epithelial-mesenchymal transition are
      associated with pulmonary metastasis in adenoid cystic carcinoma.
AB  - OBJECTIVES: Adenoid cystic carcinoma (ACC) is one of the most common malignancies
      of salivary glands, characterized by poor prognosis, particularly due to
      pulmonary metastasis. We previously reported that transforming growth factor
      (TGF)-beta1 promoted ACC cell migration and invasion via the Smad pathway in
      vitro. The aim of this study was to establish the underlying mechanisms.
      MATERIALS AND METHODS: TGF-beta1, phospho-Smad2 and beta-catenin expression in
      ACC tissues derived from patients was evaluated by immunohistochemistry. The role
      of TGF- beta1 on the invasive capacity of ACC cells was determined by transwell
      assays in SACC-83 cells transfected with TGF-beta1 and TGF-beta type II dominant
      negative receptor (TbetaRIIDN) plasmids or silenced by TGF-beta1 siRNA.
      Expression of the epithelial-mesenchymal transition (EMT) markers, beta-catenin,
      E-cadherin and Nectin-1, was determined by real-time PCR and immunochemistry. In
      vivo investigations were performed by inoculating nude mice with the transfected
      ACC cells and examining metastasis in bilateral lung tissues by
      immunohistochemistry. RESULTS: Overexpression of TGF-beta1 and phospho-Smad2, and
      reduced expression of membrane beta-catenin, were closely associated with lung
      metastasis in ACC. Furthermore, the EMT markers were downregulated. In vitro,
      cells transfected with TGF-beta1 exhibited altered morphology and increased
      invasive capacity compared to TbetaRIIDN-transfected cells or TGF-beta1 siRNA
      silenced cells. In vivo, mice inoculated with TGF-beta1 transfected ACC cells
      exhibited more metastases than other cells. CONCLUSION: TGF-beta1, phospho-Smad2
      and beta-catenin were significantly correlated with ACC metastasis. Blockade of
      TGF-beta signaling by TbetaRIIDN or siRNA may offer potential gene therapies
      against pulmonary metastasis in patients with ACC.

PMID- 23962791
TI  - Physical activity during high school recess in spanish adolescents: the AFINOS
      study.
AB  - BACKGROUND: The morning recess period during school days represents a regular
      opportunity to accumulate physical activity (PA). However, little is known about
      the contribution of recess to PA guidelines (60 min/day in moderate-to-vigorous
      PA [MVPA]) in adolescents. METHODS: This study comprised 1065 Spanish adolescents
      (52% girls), aged 13 to 16 years. Adolescents completed a validated Recess PA
      Recall in 2007-2008. Differences in levels of PA during the recess period were
      analyzed by gender, age group, type of school, school location, immigrant status,
      weight status, fitness levels and snack eating during recess. RESULTS: Adolescent
      boys spent more time in MVPA (7.7 vs. 6.4 min in MVPA, P = .009) and were more
      active (29.6% vs. 24.5% in MVPA, P = .007) than girls during the recess period.
      Adolescent boys in the youngest age group and with the school located in cities
      were more active than their peers (all P < .05). There were no differences in
      levels of PA during recess by all the descriptive characteristics in adolescent
      girls (all P > .05). CONCLUSIONS: These findings suggest that recess in Spanish
      high schools may contribute to the daily recommended MVPA for adolescents, but
      greater efforts must be implemented to increase PA levels among adolescent girls
      during this school period.

PMID- 23962793
TI  - Novel male exposure reduces uterine e-cadherin, increases uterine luminal area,
      and diminishes progesterone levels while disrupting blastocyst implantation in
      inseminated mice.
AB  - Exposure to novel male mice disrupts blastocyst implantation in inseminated
      female mice, and evidence increasingly implicates the female's absorption of male
      urinary estrogens. We observed implantation sites in male-exposed and isolated
      control female mice during gestation days (GD) 2-8, observing a significant
      reduction in male-exposed females compared to controls, particularly on GD 6 and
      8. We also measured transitions in uterine luminal area and e-cadherin
      expression, as these processes are modulated by estrogens. Luminal area was
      greater in male-exposed females than in controls during the post-implantation
      period (GD 5-7). E-cadherin levels were suppressed by male exposure, particularly
      during GD 4-6 Serum progesterone levels were also reduced in male-exposed
      females. The effects of male exposure on uterine closure and e-cadherin levels
      are consistent with established effects of estrogens, and suggest a possible
      mechanism that could contribute to implantation failure. This article is part of
      a Special Issue entitled 'Pregnancy and Steroids'. 

PMID- 23962792
TI  - Molecular basis of potassium channels in pancreatic duct epithelial cells.
AB  - Potassium channels regulate excitability, epithelial ion transport,
      proliferation, and apoptosis. In pancreatic ducts, K(+) channels hyperpolarize
      the membrane potential and provide the driving force for anion secretion. This
      review focuses on the molecular candidates of functional K(+) channels in
      pancreatic duct cells, including KCNN4 (KCa 3.1), KCNMA1 (KCa 1.1), KCNQ1 (Kv
      7.1), KCNH2 (Kv 11.1), KCNH5 (Kv 10.2), KCNT1 (KCa 4.1), KCNT2 (KCa 4.2), and
      KCNK5 (K 2P 5.1). We will give an overview of K(+) channels with respect to their
      electrophysiological and pharmacological characteristics and regulation, which we
      know from other cell types, preferably in epithelia, and, where known, their
      identification and functions in pancreatic ducts and in adenocarcinoma cells. We
      conclude by pointing out some outstanding questions and future directions in
      pancreatic K(+) channel research with respect to the physiology of secretion and
      pancreatic pathologies, including pancreatitis, cystic fibrosis, and cancer, in
      which the dysregulation or altered expression of K(+) channels may be of
      importance. 

PMID- 23962796
TI  - Predicting the environmental risks of radioactive discharges from Belgian nuclear
      power plants.
AB  - An environmental risk assessment (ERA) was performed to evaluate the impact on
      non-human biota from liquid and atmospheric radioactive discharges by the Belgian
      Nuclear Power Plants (NPP) of Doel and Tihange. For both sites, characterisation
      of the source term and wildlife population around the NPPs was provided,
      whereupon the selection of reference organisms and the general approach taken for
      the environmental risk assessment was established. A deterministic risk
      assessment for aquatic and terrestrial ecosystems was performed using the ERICA
      assessment tool and applying the ERICA screening value of 10 MUGy h(-1). The
      study was performed for the radioactive discharge limits and for the actual
      releases (maxima and averages over the period 1999-2008 or 2000-2009). It is
      concluded that the current discharge limits for the Belgian NPPs considered do
      not result in significant risks to the aquatic and terrestrial environment and
      that the actual discharges, which are a fraction of the release limits, are
      unlikely to harm the environment.

PMID- 23962794
TI  - Feasibility study of a caregiver seizure alert system in canine epilepsy.
AB  - A device capable of detecting seizures and alerting caregivers would be a major
      advance for epilepsy management, and could be used to guide early intervention
      and prevent seizure-related injuries. The objective of this work was to evaluate
      a seizure advisory system (SAS) that alerts caregivers of seizures in canines
      with naturally occurring epilepsy. Four dogs with epilepsy were implanted with a
      SAS that wirelessly transmits continuous intracranial EEG (iEEG) to an external
      device embedded with a seizure detection algorithm and the capability to alert
      caregivers. In this study a veterinarian was alerted by automated text message if
      prolonged or repetitive seizures occurred, and a rescue therapy protocol was
      implemented. The performance of the SAS caregiver alert was evaluated over the
      course of 8 weeks. Following discontinuation of antiepileptic drugs, the dogs
      experienced spontaneous unprovoked partial seizures that secondarily generalized.
      Three prolonged or repetitive seizure episodes occurred in 2 of the dogs. On each
      occasion, the SAS caregiver alert successfully alerted an on call veterinarian
      who confirmed the seizure activity via remote video-monitoring. A rescue
      medication was then administered and the seizures were aborted. This study
      demonstrates the feasibility of a SAS to alert caregivers to the occurrence of
      prolonged or repetitive seizures and enables rescue medications to be delivered
      in a timely manner. The SAS may improve the management of human epilepsy by
      alerting caregivers of seizures, enabling early interventions, and potentially
      improving outcomes and quality of life of patients and caregivers. 

PMID- 23962795
TI  - A meta-analysis of voxel-based morphometry studies on gray matter volume
      alteration in juvenile myoclonic epilepsy.
AB  - The findings of structural neuroimaging studies on gray matter volume (GMV) of
      juvenile myoclonic epilepsy (JME) with voxel-based morphometry (VBM) were
      inconsistent. We aim to evaluate consistent gray matter changes in JME
      quantitatively. A systematic review of VBM studies on GMV of patients with JME
      and healthy control (HC) subjects indexed in PubMed and EMBASE from January 1990
      to June 2012 was conducted. Coordinates were extracted from clusters of
      significant GMV difference between patients with JME and HC subjects. Meta
      analysis was performed using Effect Size Signed Differential Mapping (ES-SDM).
      Seven studies with a total of 211 JME patients and 241 HC subjects were included
      in the meta-analysis. Increased GMV were observed in the bilateral medial frontal
      gyrus and anterior cingulate, whereas decreased GMV in the bilateral thalamus.
      The findings remain largely unchanged in the jackknife sensitivity analyses. The
      meta-analysis not only identified consistent changes in some regions of gray
      matter in patients with JME, but also supports the notion of thalamocortical
      circuitry involved in the pathogenesis of JME. 

PMID- 23962797
TI  - Current understanding of organically bound tritium (OBT) in the environment.
AB  - It has become increasingly recognized that organically bound tritium (OBT) is the
      more significant tritium fraction with respect to understanding tritium behaviour
      in the environment. There are many different terms associated with OBT; such as
      total OBT, exchangeable OBT, non-exchangeable OBT, soluble OBT, insoluble OBT,
      tritiated organics, and buried tritium, etc. A simple classification is required
      to clarify understanding within the tritium research community. Unlike for
      tritiated water (HTO), the environmental quantification and behaviour of OBT are
      not well known. Tritiated water cannot bio-accumulate in the environment.
      However, it is not clear whether or not this is the case for OBT. Even though OBT
      can be detected in terrestrial biological materials, aquatic biological materials
      and soil samples, its behaviour is still in question. In order to evaluate the
      radiation dose from OBT accurately, further study will be required to understand
      OBT measurements and determine OBT fate in the environment. The relationship
      between OBT speciation and the OBT/HTO ratio in environmental samples will be
      useful in this regard, providing information on the previous tritium exposure
      conditions in the environment and the current tritium dynamics. 

PMID- 23962798
TI  - Control of NO level in rhizobium-legume root nodules: not only a plant globin
      story.
AB  - Nitric oxide (NO ) is a gaseous signaling molecule which plays both regulatory
      and defense roles in animals and plants. In the symbiosis between legumes and
      rhizobia, NO has been shown to be involved in bacterial infection and nodule
      development steps as well as in mature nodule functioning. We recently showed
      that an increase in NO level inside Medicago truncatula root nodules also could
      trigger premature nodule senescence. Here we discuss the importance of the
      bacterial Sinorhizobium meliloti flavohemoglobin to finely tune the NO level
      inside nodules and further, we demonstrate that S. meliloti possesses at least
      two non redundant ways to control NO and that both systems are necessary to
      maintain efficient nitrogen fixing activity.

PMID- 23962799
TI  - High temperature stability of anatase in titania-alumina semiconductors with
      enhanced photodegradation of 2, 4-dichlorophenoxyacetic acid.
AB  - The incorporation of aluminum acetylacetonate as alumina source during the
      gelation of titanium alkoxide reduces the nucleation sites for the formation of
      large rutile crystals on temperatures ranging from 400 to 800 degrees C. As a
      result, the aggregation of anatase crystals is prevented at high temperature. A
      relationship among the specific surface area, pore size, energy band gap,
      crystalline structure and crystallite size as the most relevant parameters are
      evaluated and discussed. According to the results for the photocatalytic
      degradation of 2,4-dichlorophenoxyacetic acid, the specific surface area, pore
      size, Eg band gap are not determinant in the photocatalytic properties. It was
      found that the anatase crystallite size is the mores important parameter
      affecting the degradation efficiency. 

PMID- 23962800
TI  - Integrated study of metal behavior in Mediterranean stream ecosystems: a case
      study.
AB  - The objective of the present work was to assess the ecosystem status of Francoli
      river (Catalonia, Spain), a Mediterranean stream basin with contrasting human
      influences. An integrated approach was designed by combining physicochemical,
      biological and ecotoxicological analyses. The content of metals (As, Cd, Cr, Co,
      Cu, Hg, Ni, Pb, and Zn) was analyzed in samples of water, benthic sediments and
      aquatic macroinvertebrates. In addition, the potentially bioavailable fraction of
      metals in water and sediments was determined by using diffusive gradient in thin
      films (DGTs) and sequential extraction of sediments (BCR), respectively. The
      biological quality was evaluated through aquatic macroinvertebrate communities,
      while the ecotoxicological status was assessed by Microtox((r)) with Vibrio
      fischeri. Finally, an analysis of acid-volatile sulfide (AVS) and simultaneously
      extracted metals (SEM) was performed to evaluate the sediment toxicity associated
      to metal content. According to the results, DGTs and BCR are suitable
      methodologies to predict the potential bioavailable fraction of metals in
      freshwater systems. Moreover, ecotoxicity evaluation by means of V. fischeri, in
      combination with the chemical characterization and the biological quality
      assessment, should be complementarily used to get a better diagnose of freshwater
      systems.

PMID- 23962801
TI  - Biotransformation of 11-keto-beta-boswellic acid by Cunninghamella blakesleana.
AB  - 11-Keto-beta-boswellic acid (KBA), as one of the active constituents in the gum
      resin of Boswellia serrata, possesses significant biological activities including
      anti-inflammatory activity. However, its extensive metabolism and low polarity
      has limited the systemic availability of KBA. The present research was aimed to
      obtain and explore the various possible derivatives of KBA through
      biotransformation by Cunninghamella blakesleana AS 3.970. A total of ten
      transformed compounds were isolated and purified, and their chemical structures
      were characterized as 7beta-hydroxy-11-keto-beta-boswellic acid; 7beta, 15alpha
      dihydroxy-11-keto-beta-boswellic acid ; 7beta, 16beta-dihydroxy-11-keto-beta
      boswellic acid; 7beta, 16alpha-dihydroxy-11-keto-beta-boswellic acid; 7beta,
      22beta-dihydroxy-11-keto-beta-boswellic acid; 7beta, 21beta-dihydroxy-11-keto
      beta-boswellic acid; 7beta, 20beta-dihydroxy-11-keto-beta-boswellic acid; 7beta,
      30-dihydroxy-11-keto-beta-boswellic acid; 3alpha, 7beta-dihydroxy-11-oxours-12
      ene-24, 30-dioic acid and 3alpha, 7beta-dihydroxy-30-(2-hydroxypropanoyloxy)-11
      oxours-12-en-24-oic acid by various spectroscopic methods. The biotransformation
      processes include hydroxylation, oxidation and esterification. Primary structure
      activity relationships (SAR) of inhibitory effects on NO production in RAW 264.7
      macrophage cells are discussed. 

PMID- 23962802
TI  - Effect of heat-shock induced oxidative stress is suppressed in BcZAT12 expressing
      drought tolerant tomato.
AB  - The transcription factor ZAT12 is a member of stress-responsive C2H2 type zinc
      finger protein (ZFP) reported to control the expression of stress-activated genes
      mediated via ROS in plants. BcZAT12-transformed tomato cv. H-86, var. Kashi
      vishesh (lines ZT1-ZT6) over-expressing the gene product is demonstrated herein
      to be tolerant to heat-shock (HS)-induced oxidative stress. Results reveal that
      the relative expression of ZAT12 as well as heat induced Hsp17.4 and Hsp21 gene
      transcripts increased in transgenic upon exposure to HS. The transformed tomato
      lines ZT1 and ZT5 had significantly lowered free radical formation, improved
      electrolyte leakage, relative water content and chlorophyll levels with an
      enhanced activities of antioxidant enzymes viz. superoxide dismutase, catalase,
      ascorbate peroxidase and glutathione reductase when exposed to HS. HS-induced
      oxidative stress by over-expression of the BcZAT12 gene transcripts in tomato as
      well as by largely enhancing the ROS-scavenging capacity and up regulation of Hsp
      transcripts. This enables the transgenic tomato plants to acquire a greater
      ability to counteract HS-induced oxidative stress, being endowed with more
      reduced antioxidant pools. The use of these HS-tolerant tomato lines could
      possibly be used for tomato cultivation in the areas affected by sudden
      temperature changes. 

PMID- 23962803
TI  - Development of a pedestrian audit tool to assess rural neighborhood walkability.
AB  - BACKGROUND: Recently, investigators have begun to refine audit instruments for
      use in rural areas. However, no studies have developed a walkability summary
      score or have correlated built environment characteristics with physical activity
      behavior. METHODS: The Rural Pedestrian Environmental Audit Instrument was
      developed specifically for use in rural areas. Segments surrounding participant's
      homes were selected to represent neighborhood streets (N = 116). Interrater
      reliability was conducted on a subset of streets (N = 42). Rural-specific domain
      and walkability scores were developed and correlated with individual-level data
      on perceptions of the neighborhood and self-reported physical activity behavior.
      RESULTS: Interrater reliability for the instrument was substantial and all
      domains had high agreement. Walkability in the audited area was low with even the
      best segments demonstrating only moderate support for walking. There were no
      significant correlations between the neighborhood walkability score and self
      reported neighborhood walkability, time spent walking, sedentary behavior, or
      BMI; however, a few correlations within the social/dynamic domain were
      significant. CONCLUSIONS: This study expands recent research refining audit
      instruments for rural areas. Findings suggest the usefulness of summarizing
      environmental data at the domain level and linking it to physical activity
      behavior to identify aspects of the neighborhood environment that are most
      strongly correlated with actual behavior.

PMID- 23962804
TI  - Stability and mobility of vacancy-H complexes in Al.
AB  - The effect of hydrogen loading on the stability and mobility of vacancy-H
      complexes in aluminum is determined by applying DFT and the minimum-mode
      following method. The binding energy per H-atom within a complex is found to
      range from -0.36 eV/atom to -0.34 eV/atom for an occupancy of, respectively, a
      single and eight H-atoms. When eight H-atoms are neighboring the vacancy the
      total binding energy becomes -2.72 eV. However, already at a load level of two H
      atoms the total binding energy reaches -0.70 eV, which fully compensates the
      vacancy creation energy. It is observed that for complexes with four or more H
      atoms the vacancy gets pinned, as the diffusion barrier increases by a factor of
      two, reaching a value of 1.03 eV or more. The explanation for the increased
      energy barrier is that at the higher hydrogen load levels the system must
      traverse an energetically unfavorable configuration where two or more H-atoms are
      separated from the vacancy. As a possible consequence of the decreased mobility
      and increased stability, highly loaded vacancy-H complexes are likely to act as
      nucleation sites for extended defects. 

PMID- 23962806
TI  - Physiological and proteomics analyses of Holm oak (Quercus ilex subsp. ballota
      [Desf.] Samp.) responses to Phytophthora cinnamomi.
AB  - Phytophthora cinnamomi is one of the agents that trigger the decline syndrome in
      Quercus spp., this being a serious threat to Mediterranean Holm oak forest
      sustainability and reforestation programs. Quercus ilex responses to Phytophthora
      cinnamomi have been studied in one-year olds seedlings from two Andalucia
      provenances, assessing the physiological water status and photosynthesis-related
      parameters. Upon inoculation with mycelium a reduction in water content,
      chlorophyll fluorescence, stomatal conductance and gas exchange was observed
      along a 90 days post inoculation period in both provenances. The reduction was
      higher in the most susceptible (SSA) provenance, than in the most tolerant (PCO),
      being these typical plant responses to drought stress. Leaf protein profiles were
      analyzed in non-inoculated and inoculated seedlings from the two provenances by
      using a 2-DE coupled to MS proteomics strategy. Ninety seven proteins changing in
      abundance in response to the inoculation were successfully identified after MALDI
      TOF-TOF analyses. The largest group of variable identified proteins were
      chloroplasts ones, and they were involved in the photosynthesis, Calvin cycle and
      carbohydrate metabolism. It was noted that a general tendency was a decrease in
      the protein abundance as a consequence of the inoculation, being it less accused
      in the least susceptible, the Northern provenance (PCO), than in the most
      susceptible, the Southern provenance (SSA). This trend is clearly manifested in
      photosynthesis, amino acid metabolism and stress/defence proteins. On the
      contrary, some proteins related to starch biosynthesis, glycolysis and stress
      related peroxiredoxin showed an increase upon inoculation. These changes in
      protein abundance were correlated to the estimated physiological parameters and
      have been frequently observed in plants subjected to drought stress. 

PMID- 23962805
TI  - Nuclear pore proteins regulate chromatin structure and transcriptional memory by
      a conserved mechanism.
AB  - Previous experience alters the rate of transcriptional induction of many genes in
      yeast and this phenomenon persists through several cell division cycles. This
      phenomenon is called epigenetic transcriptional memory. For the yeast gene INO1,
      transcriptional memory requires a physical interaction with the nuclear pore
      complex (NPC) and changes in the chromatin structure of the promoter. These
      changes lead to binding of a preinitiation form of RNA Polymerase II (RNAPII) to
      the INO1 promoter, bypassing the need to recruit RNAPII to the promoter during
      reactivation. In our recent study, we found that in human cells, hundreds of
      interferon-gamma responsive genes exhibit a mechanistically similar form of
      transcriptional memory. Transcriptional memory requires a homologous nuclear pore
      protein in yeast and humans, which interacts with the promoters of genes that
      exhibit transcriptional memory and promotes both alteration of chromatin
      structure and binding of RNAPII. Whereas the interaction of yeast genes with
      nuclear pore proteins occurs at the NPC, the interaction of human genes with
      nuclear pore proteins occurs in the nucleoplasm. Thus, the interaction of nuclear
      pore proteins with genes plays an important and conserved role in affecting long
      term epigenetic changes in transcriptional regulation. 

PMID- 23962807
TI  - Histamine H(4) receptor antagonists ineffective against itch and skin
      inflammation in atopic dermatitis mouse model.

PMID- 23962808
TI  - NKG2D triggers cytotoxicity in murine epidermal gammadelta T cells via PI3K
      dependent, Syk/ZAP70-independent signaling pathway.
AB  - Murine epidermal gammadelta T cells, known as dendritic epidermal T cells
      (DETCs), survey tissue stress through the invariant T-cell receptor (TCR) and non
      clonotypic receptors such as NKG2D. NKG2D signaling via the DAP10
      phosphatidylinositol 3-kinase (PI3K) pathway directly stimulates cytotoxicity in
      natural killer (NK) cells and costimulates CD8(+) T cells to augment TCR signals.
      In activated murine NK cells, NKG2D signals also via the DAP12-Syk/ZAP70 pathway
      that triggers both cytotoxicity and cytokine production. It remains controversial
      whether NKG2D on DETCs is a primary activating receptor or functions only as a
      costimulatory receptor, and signaling pathways initiated by NKG2D ligation in
      DETCs have not been analyzed. We show that stimulation of short-term DETC lines
      with recombinant NKG2D ligands triggers degranulation (exocytosis of cytotoxic
      granules) via the PI3K-dependent signaling pathway, but does not induce cytokine
      production or Syk/ZAP70 activation. Coengagement of TCR or Syk/ZAP70 signaling
      was not crucial for DETC-mediated killing of NKG2D ligand-expressing target
      cells. Thus, NKG2D can function as a coactivating stress receptor that directly
      triggers cytotoxicity in DETCs, at least after priming, via the PI3K-dependent,
      Syk/ZAP70-independent signaling pathway. 

PMID- 23962809
TI  - MicroRNA expression patterns related to merkel cell polyomavirus infection in
      human merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is an aggressive and lethal type of neuroendocrine
      skin cancer. Mutated Merkel cell polyomavirus (MCV) is commonly found in MCC, and
      leads to upregulation of the survivin oncogene. However, ~20% of MCC tumors do
      not have detectable MCV, suggesting alternative etiologies for this tumor type.
      In this study, our aim was to evaluate microRNA (miRNA) expression profiles and
      their associations with MCV status and clinical outcomes in MCC. We showed that
      miRNA expression profiles were distinct between MCV-positive (MCV+) and MCV
      negative (MCV-) MCCs and further validated that miR-203, miR-30a-3p, miR-769-5p,
      miR-34a, miR-30a-5p, and miR-375 were significantly different. We also identified
      a subset of miRNAs associated with tumor metastasis and MCC-specific survival.
      Functionally, overexpression of miR-203 was found to inhibit cell growth, induce
      cell cycle arrest, and regulate survivin expression in MCV- MCC cells, but not in
      MCV+ MCC cells. Our findings reveal a mechanism of survivin expression regulation
      in MCC cells, and provide insights into the role of miRNAs in MCC tumorigenesis. 

PMID- 23962810
TI  - Keratin 9 is required for the structural integrity and terminal differentiation
      of the palmoplantar epidermis.
AB  - Keratin 9 (K9) is a type I intermediate filament protein whose expression is
      confined to the suprabasal layers of the palmoplantar epidermis. Although
      mutations in the K9 gene are known to cause epidermolytic palmoplantar
      keratoderma, a rare dominant-negative skin disorder, its functional significance
      is poorly understood. To gain insight into the physical requirement and
      importance of K9, we generated K9-deficient (Krt9(-/-)) mice. Here, we report
      that adult Krt9(-/-)mice develop calluses marked by hyperpigmentation that are
      exclusively localized to the stress-bearing footpads. Histological,
      immunohistochemical, and immunoblot analyses of these regions revealed
      hyperproliferation, impaired terminal differentiation, and abnormal expression of
      keratins K5, K14, and K2. Furthermore, the absence of K9 induces the stress
      activated keratins K6 and K16. Importantly, mice heterozygous for the K9-null
      allele (Krt9(+/-)) show neither an overt nor histological phenotype,
      demonstrating that one Krt9 allele is sufficient for the developing normal
      palmoplantar epidermis. Together, our data demonstrate that complete ablation of
      K9 is not tolerable in vivo and that K9 is required for terminal differentiation
      and maintaining the mechanical integrity of palmoplantar epidermis. 

PMID- 23962811
TI  - Mild mitochondrial uncoupling prevents premature senescence in human dermal
      fibroblasts.

PMID- 23962812
TI  - Generalized pustular psoriasis triggered by amoxicillin in monozygotic twins with
      compound heterozygous IL36RN mutations: comment on the article by Navarini et al.

PMID- 23962813
TI  - The generation of higher-order Laguerre-Gauss optical beams for high-precision
      interferometry.
AB  - Thermal noise in high-reflectivity mirrors is a major impediment for several
      types of high-precision interferometric experiments that aim to reach the
      standard quantum limit or to cool mechanical systems to their quantum ground
      state. This is for example the case of future gravitational wave observatories,
      whose sensitivity to gravitational wave signals is expected to be limited in the
      most sensitive frequency band, by atomic vibration of their mirror masses. One
      promising approach being pursued to overcome this limitation is to employ higher
      order Laguerre-Gauss (LG) optical beams in place of the conventionally used
      fundamental mode. Owing to their more homogeneous light intensity distribution
      these beams average more effectively over the thermally driven fluctuations of
      the mirror surface, which in turn reduces the uncertainty in the mirror position
      sensed by the laser light. We demonstrate a promising method to generate higher
      order LG beams by shaping a fundamental Gaussian beam with the help of
      diffractive optical elements. We show that with conventional sensing and control
      techniques that are known for stabilizing fundamental laser beams, higher-order
      LG modes can be purified and stabilized just as well at a comparably high level.
      A set of diagnostic tools allows us to control and tailor the properties of
      generated LG beams. This enabled us to produce an LG beam with the highest purity
      reported to date. The demonstrated compatibility of higher-order LG modes with
      standard interferometry techniques and with the use of standard spherical optics
      makes them an ideal candidate for application in a future generation of high
      precision interferometry.

PMID- 23962814
TI  - Explanations about possible misinterpretation of the terminology regarding to
      bovine tuberculosis status of one cattle herd in Spain, arisen from the paper
      "Reducing Eurasian wild boar (Sus scrofa) population density as a measure for
      bovine tuberculosis control: Effects in wild boar and a sympatric fallow deer
      (Dama dama) population in Central Spain", [Prev. Vet. Med. 110 (July (3-4))
      (2013) 435-446].

PMID- 23962815
TI  - RKKY interaction in heavily vacant graphene.
AB  - Dirac electrons in clean graphene can mediate the interactions between two
      localized magnetic moments. The functional form of the RKKY interaction in
      pristine graphene is specified by two main features: (i) an atomic-scale
      oscillatory part determined by a wavevector Q connecting the two valleys; with
      doping another longer range oscillation appears which arises from the existence
      of an extended Fermi surface characterized by a momentum scale kF; (ii) an
      algebraic R(alpha) decay in large distances where the exponent alpha =- 3 is a
      distinct feature of undoped Dirac sea in two dimensions. In this work, we
      investigate the effect of a few per cent vacancies on the above properties.
      Depending on the doping level, if the chemical potential lies on the linear part
      of the density of states, the exponent alpha remains at -3 even in vacant
      graphene. Otherwise alpha reduces towards more negative values. Presence of
      vacancies washes out both atomic-scale and Friedel oscillations of the RKKY
      interaction. The absence of atomic-scale oscillations indicates the destruction
      of two-valley structure of the parent graphene material. However, the absence of
      Friedel oscillations upon 'alloying' with vacancies indicates that a quantum
      ground state of heavily vacant doped graphene is not given by a unique kF
      momentum scale.

PMID- 23962816
TI  - Temporal patterns of odorant receptor gene expression in adult and aged mice.
AB  - In the mouse, the sense of smell relies predominantly on the expression of ~1200
      odorant receptor (OR) genes in the main olfactory epithelium (MOE). Each mature
      olfactory sensory neuron (OSN) in the MOE is thought to express just one of these
      OR genes; conversely, an OR gene is expressed in thousands to tens of thousands
      of OSNs per mouse. Here, we have characterized temporal patterns of OR gene
      expression in a cohort of inbred C57BL6/N mice from the Aged Rodent Colonies of
      the National Institute on Aging. We applied the NanoString multiplex platform to
      quantify RNA abundance for 531 OR genes in whole olfactory mucosa (WOM) tissue
      samples. The five study groups were females aged 2, 6, 12, 18, and 31 months
      (mo). We classified the 531 temporal patterns using a step-down quadratic
      regression method for time course analysis. The majority of OR genes (58.4%) are
      classified as flat: there is no significant difference from a horizontal line
      within this time window. There are 32.8% of OR genes with a downward profile,
      7.2% with an upward profile, and 1.7% with a convex or concave profile. But the
      magnitude of these decreases and increases tends to be small: only 4.3% of OR
      genes are differentially expressed (DE) at 31 mo compared to 2 mo. Interestingly,
      the variances of NanoString counts for individual OR genes are homogeneous among
      the age groups. Our analyses of these 15,930 OR gene expression data of C57BL6/N
      mice that were raised and housed under well-controlled conditions indicate that
      OR gene expression at the MOE level is intrinsically stable.

PMID- 23962817
TI  - Pathways of iron acquisition and utilization in Leishmania.
AB  - Iron is essential for many metabolic pathways, but is toxic in excess. Recent
      identification of the ferric iron reductase LFR1, the ferrous iron transporter
      LIT1, and the heme transporter LHR1 greatly advanced our understanding of how
      Leishmania parasites acquire iron and regulate its uptake. LFR1 and LIT1 have
      close orthologs in plants, and are required for Leishmania virulence. Consistent
      with the lack of heme biosynthesis in trypanosomatids, LHR1 and LABCG5, a protein
      involved in heme salvage from hemoglobin, seem essential for Leishmania survival.
      LFR1, LIT1 and LHR1 are upregulated under low iron availability, in agreement
      with the need to prevent excessive iron uptake. Future studies should clarify how
      Leishmania interacts with the iron homeostasis machinery of its host cell, the
      macrophage. 

PMID- 23962818
TI  - Iron sparing and recycling in a compartmentalized cell.
AB  - This review focuses on economizing, prioritizing and recycling iron in
      Chlamydomonas, a reference organism for discovering mechanisms of acclimation to
      poor iron nutrition in the plant lineage. The metabolic flexibility of
      Chlamydomonas offers a unique opportunity to distinguish the impact of iron
      nutrition on photosynthetic versus respiratory metabolism, and the contribution
      of subcellular compartments to iron storage and mobilization. Mechanisms of iron
      sparing include down regulation of protein abundance by transcript reduction or
      protein degradation. Two well-studied examples of hierarchical iron allocation
      are the maintenance of FeSOD in the plastid and heterotrophic metabolism in
      acetate-grown cells at the expense of photosynthetic metabolism. The latter
      implicates the existence of a pathway for inter-compartment iron recycling when
      access to iron becomes limiting. 

PMID- 23962819
TI  - Iron sensing and regulation in Saccharomyces cerevisiae: Ironing out the
      mechanistic details.
AB  - Regulation of iron metabolism in Saccharomyces cerevisiae is achieved at the
      transcriptional level by low (Aft1 and Aft2) and high iron-sensing (Yap5)
      transcription factors, and at the post-transcriptional level by mRNA-binding
      proteins (Cth1 and Cth2). In this review we highlight recent studies unveiling
      the critical role that iron-sulfur clusters play in control of Aft1/2 and Yap5
      activity, as well as the complex relationship between iron homeostasis and thiol
      redox metabolism. In addition, new insights into the localization and regulation
      of Cth1/Cth2 have added another layer of complexity to the cell's adaptation to
      iron deficiency. Finally, biophysical studies on subcellular iron speciation
      changes in response to environmental and genetic factors have further illuminated
      the elaborate control mechanisms required to manage iron bioavailability in the
      cell. 

PMID- 23962820
TI  - The crucial role of iron uptake in Aspergillus fumigatus virulence.
AB  - Aspergillus fumigatus is an opportunistic fungal pathogen that causes life
      threatening infections in immunocompromised individuals. Siderophore-mediated
      iron acquisition has been shown to be essential for virulence. New studies have
      revealed that enzymes involved in siderophore biosynthesis and uptake are
      compartmentalized in peroxisomes and endosome-like vesicles, respectively. Gene
      and protein expression studies have revealed coordinated regulation of
      siderophore and sterol metabolism linked to the common precursor mevalonate.
      Several A. fumigatus transcription factors have been identified that are
      unexpectedly involved in the regulation of iron homeostasis. New diagnostic and
      drug treatments are being developed that exploit the requirement of A. fumigatus
      for extracellular siderophores. 

PMID- 23962821
TI  - Assessment of the performance of the Marsh model in effect site mode for target
      controlled infusion of propofol during the maintenance phase of general
      anaesthesia in an unselected population of neurosurgical patients.
AB  - BACKGROUND: Propofol target-controlled infusion (TCI) in effect site mode has
      become popular since it became commercially available. OBJECTIVE: We have
      performed a study to assess the pharmacokinetic performance of the Marsh model in
      effect site mode in an unselected group of patients during neurosurgery during
      the maintenance phase of anaesthesia. DESIGN: Fifty American Society of
      Anesthesiologists (ASA) physical status classes 1 to 3 adults underwent elective
      neurosurgery receiving propofol TCI using the Marsh model in effect site mode.
      Propofol dose titration and level of patient monitoring was determined by the
      attending anaesthesiologist. Arterial blood was sampled at regular intervals
      during the maintenance phase of anaesthesia and measured plasma propofol
      concentrations were compared with those estimated using TCI. SETTING: Large
      tertiary referral centre in Birmingham, UK, with a specialist neuroanaesthesia
      service. PATIENTS: Fifty ASA status I to III adult patients undergoing elective
      neurosurgery. MAIN OUTCOME MEASURES: Performance of Marsh model as assessed by
      median performance error (bias) and median absolute performance error
      (imprecision). RESULTS: Performance of the Marsh model showed a positive bias
      (median performance error) of 27.6%, and imprecision (median absolute performance
      error) of 29.4%. Analysis of pooled data demonstrated greatest bias in the early
      phase (15 to 30 min) of anaesthesia (mean prediction error of 51.6%). Analysis of
      covariates demonstrated that obesity (BMI >30 kg m(-2)) contributed around half
      of the bias detected (mean prediction error 47 vs. 23%, P < 0.001). Patients with
      advanced age and significant comorbidity (ASA physical status class >2) actually
      demonstrated significantly lower prediction errors. CONCLUSION: Pharmacokinetic
      analysis suggests that the performance of the Marsh model in effect site mode is
      poor in this broad patient population. The greatest bias demonstrated occurred in
      the early maintenance phase of anaesthesia. Of the covariates analysed, obesity
      contributed most significantly to an increased bias. Despite overall poor
      performance of the Marsh model, attending anaesthesiologists modified targeted
      propofol concentrations only 0.3 times per hour on average, using remifentanil
      dose modification nine times more frequently, with good surgical conditions in
      all patients.

PMID- 23962823
TI  - Activation of extracellular signal-regulated kinase in the trigeminal ganglion
      following both treatment of the dura mater with capsaicin and cortical spreading
      depression.
AB  - Extracellular signal-regulated kinase (ERK) is known to be phosphorylated after
      exposure to noxious stimuli. In this study, we investigated the response in the
      dura mater to nociceptive stimulation, which is thought to be responsible for the
      pathogenesis of headaches, including migraines. We also examined the level of ERK
      phosphorylation in the trigeminal ganglion following cortical spreading
      depression (CSD), which is thought to play an important role in migraine
      pathophysiology. Western blot and immunohistochemical analyses showed a
      significant increase in the ERK phosphorylation levels 3 min following an
      application of 10mM capsaicin to the dura mater. This increase was inhibited
      after an application of the TRPV1 antagonist capsazepine or a MEK inhibitor. An
      immunohistochemical analysis revealed that most of the small-sized trigeminal
      ganglion neurons with TRPV1-immunoreactivity that innervate the dura mater
      exhibited pERK-immunoreactivity, suggesting that these neurons had responded to
      nociceptive stimulation. CSD increased the level of ERK phosphorylation 30 min
      after its elicitation, and this response was inhibited by a prior
      intraventricular administration of TRPV1 antagonist. These results indicate that
      CSD can activate dural TRPV1 to send nociceptive signals to the trigeminal
      system, and they provide important clues regarding the relationship between CSD
      and the trigeminovascular system.

PMID- 23962824
TI  - Localized enrichment of polycyclic aromatic hydrocarbons in soil, spruce needles,
      and lake sediments linked to in-situ bitumen extraction near Cold Lake, Alberta.
AB  - The extraction of bitumen from the Alberta oil sands using in-situ technologies
      is expanding at a rapid rate; however, investigations into the environmental
      impacts of oil sands development have focused on surface mining in the Athabasca
      region. We measured polycyclic aromatic hydrocarbons (PAH) in soils, spruce
      needles, and lake sediment cores in the Cold Lake oil sands region to provide a
      historical and spatial perspective on PAH contamination related to in-situ
      extraction activities. A pronounced increase in PAH concentrations was recorded
      in one of two study lakes (Hilda Lake) corresponding to the onset of commercial
      bitumen production in ~1985. Distance from extraction rigs was not an important
      predictor of PAH concentrations in soils, although two samples located near
      installations were elevated in alkyl PAHs. Evidence of localized PAH
      contamination in Hilda Lake and two soil samples suggests that continued
      environmental monitoring is justified to assess PAH contamination as development
      intensifies.

PMID- 23962822
TI  - The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis.
AB  - The discovery of Helicobacter pylori overturned the conventional dogma that the
      stomach was a sterile organ and that pH values<4 were capable of sterilizing the
      stomach. H. pylori are an etiological agent associated with gastritis,
      hypochlorhydria, duodenal ulcers, and gastric cancer. It is now appreciated that
      the human stomach supports a bacterial community with possibly 100s of bacterial
      species that influence stomach homeostasis. Other bacteria colonizing the stomach
      may also influence H. pylori-associated gastric pathogenesis by creating reactive
      oxygen and nitrogen species and modulating inflammatory responses. In this
      review, we summarize the available literature concerning the gastric microbiota
      in humans, mice, and Mongolian gerbils. We also discuss the gastric
      perturbations, many involving H. pylori, that facilitate the colonization by
      bacteria from other compartments of the gastrointestinal tract, and identify risk
      factors known to affect gastric homeostasis that contribute to changes in the
      microbiota. 

PMID- 23962825
TI  - Functional role, mechanisms of regulation, and therapeutic potential of regulator
      of G protein signaling 2 in the heart.
AB  - G protein-mediated signal transduction is essential for the regulation of
      cardiovascular function, including heart rate, growth, contraction, and vascular
      tone. Regulators of G protein Signaling (RGS proteins) fine-tune G protein
      coupled receptor-induced signaling by regulating its magnitude and duration
      through direct interaction with the alpha subunits of heterotrimeric G proteins.
      Changes in the RGS protein expression and/or function in the heart often lead to
      pathophysiological changes and are associated with cardiac disease in animals and
      humans, including hypertrophy, fibrosis development, heart failure, and
      arrhythmias. This article focuses on Regulator of G protein Signaling 2 (RGS2),
      which is widely expressed in many tissues and is highly regulated in its
      expression and function. Most information to date has been obtained in
      biochemical, cellular, and animal studies, but data from humans is emerging. We
      review recent advances on the functional role of cardiovascular RGS2 and the
      mechanisms that determine its signaling selectivity, expression, and
      functionality. We highlight key unanswered questions and discuss the potential of
      RGS2 as a therapeutic target. 

PMID- 23962826
TI  - Transmission of Ehrlichia canis by Rhipicephalus sanguineus ticks feeding on dogs
      and on artificial membranes.
AB  - A South African strain of Ehrlichia canis was isolated and used to infect a
      laboratory-bred Beagle dog. Rhipicephalus sanguineus nymphs, which fed on this
      dog, moulted to adult ticks which carried infection rates of E. canis between 12%
      and 19% and were used in a series of in vivo and in vitro experiments. Five
      groups of 6 dogs were challenged with the infected R. sanguineus ticks, which
      were removed 24h, 12h, 6h or 3h after the ticks had been released onto the dogs.
      The animals were monitored for fever and thrombocytopenia and were considered
      infected if they became serologically positive for E. canis antibodies as well as
      PCR positive for E. canis DNA. Seven dogs became infected with E. canis in the
      following groups: Group 1 (24h tick challenge) 1 out of 6; Group 2 (12h) 1 of 6;
      Group 3 (6h) 2 of 6; Group 4 (6h) 2 of 6 and Group 5 (3h) 1 out of 6. Six of
      those 7 infected dogs developed fever and a significant thrombocytopenia. One dog
      did not show any symptoms, but seroconverted and was found PCR positive on
      several occasions. Five additional dogs were PCR positive on one test sample only
      but were not considered infected because they did not develop any specific E.
      canis antibodies. In vitro, R. sanguineus ticks attached and fed on bovine blood
      through silicone membranes with attachment rates up to 72.5% after 24h increasing
      to 84.2% at 72 h. The ticks transmitted E. canis as soon as 8h post application
      as demonstrated by E. canis DNA found in the nutritive blood medium. In
      conclusion, transmission of E. canis by R. sanguineus ticks starts within a few
      hours after attachment, which is earlier than previously thought. These findings
      underpin the need for acaricides to provide either a repellent, an anti
      attachment and/or a rapid killing effect against ticks in order to decrease the
      risk of transmission of E. canis.

PMID- 23962827
TI  - Metacognitive and social cognition training (MSCT) in schizophrenia: a
      preliminary efficacy study.
AB  - Psychosocial interventions have proven to be effective in treating social
      cognition in people with psychotic disorders. The current study aimed to
      determine the effects of a metacognitive and social cognition training (MSCT)
      program, designed to both remediate deficits and correct biases in social
      cognition. Thirty-five clinically stable outpatients were recruited and assigned
      to the MSCT program (n=19) for 10 weeks (18 sessions) or to the TAU group (n=16),
      and they all completed pre- and post-treatment assessments of social cognition,
      cognitive biases, functioning and symptoms. The MSCT group demonstrated a
      significant improvement in theory of mind, social perception, emotion recognition
      and social functioning. Additionally, the tendency to jump to conclusions was
      significantly reduced among the MSCT group after training. There were no
      differential benefits regarding clinical symptoms except for one trend group
      effect for general psychopathology. The results support the efficacy of the MSCT
      format, but further development of the training program is required to increase
      the benefits related to attributional style.

PMID- 23962828
TI  - Neurocognitive individualized training versus social skills individualized
      training: a randomized trial in patients with schizophrenia.
AB  - Rehabilitation programs integrating cognitive remediation (CR) and psychosocial
      rehabilitation are often implemented as they seem to yield greater improvements
      in functional outcome than stand alone treatment approaches. Mechanisms
      underlying synergistic effects of combining CR with psychosocial interventions
      are not fully understood. Disentangling the relative contribution of each
      component of integrated programs might improve understanding of underlying
      mechanisms. In the present study we compared the efficacy of two components of
      our rehabilitation program [the Neurocognitive Individualized Training (NIT) and
      the Social Skills Individualized Training (SSIT)]. Seventy-two patients with
      schizophrenia or schizoaffective disorder were randomly assigned to one of two
      treatment groups. Changes in cognitive, psychopathological and real-world
      functioning indices after 6 and 12 months were compared between the two groups.
      After both 6 and 12 months, NIT produced an improvement of attention, verbal
      memory and perseverative aspects of executive functioning, while SSIT produced a
      worsening of visuo-spatial memory and attention and no significant effect on the
      other cognitive domains. As to the real-world functioning, NIT produced a
      significant improvement of interpersonal relationships, while SSIT yielded a
      significant improvement of QLS instrumental role subscale. According to our
      findings, cognitive training is more effective than social skills training on
      several cognitive domains and indices of real-world functioning relevant to
      subject's relationships with other people. Integrated approaches might target
      different areas of functional impairment but should be planned carefully and
      individually to fully exploit the synergistic potential.

PMID- 23962829
TI  - Nosology of psychoses in DSM-5: inches ahead but miles to go.

PMID- 23962830
TI  - Is shock index associated with outcome in children with sepsis/septic shock?*.
AB  - OBJECTIVES: To investigate the association between PICU shock index (the ratio of
      heart rate to systolic blood pressure) and PICU mortality in children with
      sepsis/septic shock. To explore cutoff values for shock index for ICU mortality,
      how change in shock index over the first 6 hours of ICU admission is associated
      with outcome, and how the use of vasoactive therapy may affect shock index and
      its association with outcome. DESIGN: Retrospective cohort. SETTING: Single
      center tertiary PICU. SUBJECTS: Five hundred forty-four children with the
      diagnosis of sepsis/septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: From January 2003 to December 2009, 544 children met International
      Pediatric Sepsis Consensus Conference of 2005 criteria for sepsis/septic shock.
      Overall mortality was 23.7%. Among all patients, hourly shock index was
      associated with mortality: odds ratio of ICU mortality at 0 hour, 1.08, 95% CI
      (1.04-1.12); odds ratio at 1 hour, 1.09 (1.04-1.13); odds ratio at 2 hours, 1.09
      (1.05-1.13); and odds ratio at 6 hours, 1.11 (1.06-1.15). When stratified by age,
      early shock index was associated with mortality only in children 1-3 and more
      than or equal to 12 years old. Area under the receiver operating characteristic
      curve in age 1-3 and more than or equal to 12 years old for shock index at
      admission was 0.69 (95% CI, 0.58-0.80) and 0.62 (95% CI, 0.52-0.72) respectively,
      indicating a fair predictive marker. Although higher shock index was associated
      with increased risk of mortality, there was no particular cutoff value with
      adequate positive or negative likelihood ratios to identify mortality in any age
      group of children. The improvement of shock index in the first 6 hours of ICU
      admission was not associated with outcome when analyzed in all patients. However,
      among patients whose shock index were above the 50th percentile at ICU admission
      for each age group, improvement of shock index was associated with lower ICU
      mortality in children between 1-3 and more than or equal to 12 years old (p =
      0.02 and p = 0.03, respectively). When controlling for the use of vasoactive
      therapy within the first 6 hours with logistic regression analysis, shock index
      at hour 6 remained significantly associated with mortality (odds ratio, 1.09; 95%
      CI, 1.05-1.14). CONCLUSIONS: Shock index may have promise as a marker of
      mortality in children with sepsis/septic shock. Although there is no clear cutoff
      shock index to identify risk of mortality, given the higher risk of mortality as
      shock index increases, children with elevated shock index may benefit from more
      aggressive resuscitation and higher level of care.

PMID- 23962831
TI  - Changes in transfusion practice over time in the PICU.
AB  - OBJECTIVES: Recent randomized clinical trials have shown the efficacy of a
      restrictive transfusion strategy in critically ill children. The impact of these
      trials on pediatric transfusion practice is unknown. Additionally, long-term
      trends in pediatric transfusion practice in the ICU have not been described. We
      assessed transfusion practice over time, including the effect of clinical trial
      publication. DESIGN: Single-center, retrospective observational study. SETTING: A
      10-bed PICU in an urban academic medical center. PATIENTS: Critically ill,
      nonbleeding children between the ages of 3 days and 14 years old, admitted to the
      University of Maryland Medical Center PICU between January 1, 1998, and December
      31, 2009, excluding those with congenital heart disease, hemolytic anemia, and
      hemoglobinopathies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During
      the time period studied, 5,327 patients met inclusion criteria. Of these, 335
      received at least one RBC transfusion while in the PICU. The overall proportion
      transfused declined from 10.5% in 1998 to 6.8% in 2009 (p = 0.007). Adjusted for
      acuity, the likelihood of transfusion decreased by calendar year of admission. In
      transfused patients, the pretransfusion hemoglobin level declined, from 10.5 g/dL
      to 9.3 g/dL, though these changes failed to meet statistical significance (p =
      0.09). Neonatal age, respiratory failure, shock, multiple organ dysfunction
      syndrome, and acidosis were associated with an increased likelihood of
      transfusion in both univariate and multivariable models. CONCLUSIONS: The overall
      proportion of patients transfused between 1998 and 2009 decreased significantly.
      The magnitude of the decrease varied over time, and no additional change in
      transfusion practice occurred after the publication of a major pediatric clinical
      trial in 2007. Greater illness acuity and younger patient age were associated
      with an increased likelihood of transfusion.

PMID- 23962832
TI  - Psychometric evaluation of the Sophia Observation withdrawal symptoms scale in
      critically ill children.
AB  - OBJECTIVE: The Sophia Observation withdrawal Symptoms scale is an instrument for
      screening benzodiazepine and opioid withdrawal syndrome in pediatric critical
      care patients. The objectives of this study were to establish cutoff scores and
      to test sensitivity to change. Second, risk factors for withdrawal syndrome were
      explored. DESIGN: Prospective observational study with repeated measures.
      SETTING: Level IV ICU at a university children's hospital. PATIENTS: A total of
      154 children with median age 5 months (interquartile range, 0-42 mo) who received
      continuous infusion of benzodiazepines and/or opioids for 5 or more days.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nurses repeatedly applied the
      Sophia Observation withdrawal Symptoms scale and the Numeric Rating Scale
      withdrawal when children were weaned off benzodiazepines and opioids. The latter
      represents the nurse's expert opinion. We analyzed 3,754 paired assessments; the
      median number per child was 15 (interquartile range, 7-31) over a median of 5
      days (interquartile range, 3-11 d). Sensitivity and specificity were 0.83 and
      0.93, respectively, for the Sophia Observation withdrawal Symptoms scale cutoff
      score of 4 or higher against a Numeric Rating Scale-withdrawal score of 4 or
      higher. Sensitivity to change was determined by comparing 156 Sophia Observation
      withdrawal Symptoms scale assessments (n = 51 patients) before and after
      additional sedatives or opioids. Multilevel regression analysis showed a mean
      decline of 1.5 points (at score range 0-15) after intervention (p < 0.0001).
      Logistic regression analysis identified duration of preweaning of midazolam,
      duration of weaning of midazolam, duration of preweaning of morphine, duration of
      weaning of morphine, and number of additional sedatives/opioids as statistically
      significant risk factors for withdrawal syndrome in these children. CONCLUSIONS:
      The Sophia Observation withdrawal Symptoms scale is a valid tool with good
      psychometric properties to assess withdrawal symptoms in PICU patients.

PMID- 23962833
TI  - Opioid use after cardiac surgery in children with Down syndrome.
AB  - OBJECTIVES: To determine the cumulative opioid doses administered to patients
      with Down syndrome after cardiac surgery and compare them with patients without
      Down syndrome. DESIGN: Retrospective observational comparative study. SETTING:
      PICU in a university-affiliated freestanding pediatric teaching hospital.
      PATIENTS: Infants and children who presented to our institution for heart surgery
      after July 1, 2008, and met the following criteria: 1) no opioid medications for
      48 hours prior to surgery, 2) sternotomy approach with primary closure, and 3) no
      additional operative procedures in the 5 days after surgery. All patients with
      Down syndrome were included, and patients without Down syndrome with similar age,
      type of cardiac lesion, and length of surgical procedure were selected in a ~2:1
      ratio, blinded to opioid exposure. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Clinical and demographic data were extracted from electronic medical
      record data. Univariate analyses and multivariate linear regression modeling were
      performed to determine the influence of Down syndrome, patient characteristics,
      and clinical covariates on weight-adjusted opioid dose. The differences in median
      cumulative opioid doses between those with Down syndrome (n = 44) and those
      without Down syndrome (n = 77) were not significant in the first 24 hours (+0.39
      mg/kg [95% CI, -0.45 to +1.39 mg/kg]) or 96 hours (+0.54 mg/kg [95% CI, -0.59 to
      +2.07 mg/kg]) after surgery. Age, cardiac bypass time, benzodiazepines, and
      neuromuscular blocking agents were significantly correlated with opioid dose, but
      Down syndrome, gender, pain score, creatinine, acetaminophen, nonsteroidal anti
      inflammatory drugs, and steroid medications were not. Patients with Down syndrome
      had longer hospital stays; in multivariate analysis, higher opioid exposures in
      the first 96 hours after surgery and higher peak serum creatinine values
      correlated with longer hospitalization. CONCLUSIONS: This cohort did not provide
      evidence for opioid resistance in patients with Down syndrome. Younger age,
      longer cardiac bypass time, exposure to benzodiazepines, and neuromuscular
      blockade did correlate with increased opioid doses after cardiac surgery.

PMID- 23962834
TI  - MRI-based anatomical landmarks for the identification of thoracic vertebral
      levels.
AB  - AIM: To identify soft-tissue and bony anatomical landmarks on dedicated thoracic
      spine magnetic resonance imaging (MRI), and to assess their detectability,
      reproducibility, and accuracy in predicting specific thoracic vertebral levels.
      MATERIALS AND METHODS: One hundred dedicated thoracic MRI studies were
      retrospectively analysed by two radiologists independently. Ten bone and soft
      tissue landmarks were localized to the adjacent vertebral level. The true
      numerical thoracic vertebral level was subsequently determined and recorded by
      cross referencing with a sagittal cervico-thoracic "counting scan". RESULTS: Six
      landmarks were defined in >=98% cases; however, there was a low interobserver
      percentage agreement for the defined vertebral levels (>70% for only one
      landmark). The most useful landmark for defining a specific vertebral level was
      the most superior rib (98% detection, 95% interobserver agreement, 98% at a
      single vertebral level, 0.07 SD). Eight landmarks localized to a specific
      thoracic segment in only 16-44% of cases, with a standard deviation of >0.5
      vertebral levels and with a range which was greater than four vertebral levels.
      CONCLUSION: The C2 vertebra must be identified and cross referenced to the
      dedicated thoracic spine MRI, as other MRI-based anatomical landmarks are
      unreliable in determining the correct thoracic vertebral level.

PMID- 23962835
TI  - Fabrication of VB2/air cells for electrochemical testing.
AB  - A technique to investigate the properties and performance of new multi-electron
      metal/air battery systems is proposed and presented. A method for synthesizing
      nanoscopic VB2 is presented as well as step-by-step procedure for applying a
      zirconium oxide coating to the VB2 particles for stabilization upon discharge.
      The process for disassembling existing zinc/air cells is shown, in addition
      construction of the new working electrode to replace the conventional zinc/air
      cell anode with a the nanoscopic VB2 anode. Finally, discharge of the completed
      VB2/air battery is reported. We show that using the zinc/air cell as a test bed
      is useful to provide a consistent configuration to study the performance of the
      high-energy high capacity nanoscopic VB2 anode.

PMID- 23962836
TI  - Methods of peripheral nerve tissue preparation for second harmonic generation
      imaging of collagen fibers.
AB  - Second harmonic generation (SHG) imaging of the peripheral nerve using multi
      photon microscopy is a novel technique with little documentation. It affords the
      significant possibility of non-destructive imaging of internal nerve anatomy. The
      nature of nerve tissue, especially its size and viscoelastic properties, present
      special challenges for microscopy. While nerves are under an innate in situ
      strain, they retract once dissected, thus distorting microscopic structure. The
      challenge is to preserve the nerve in its natural strain range to obtain images
      that most truly reveal its structure. This study examined backscattered SHG
      images of rat median nerve prepared by several different methods to compare image
      quality and content. Nerve segments were fixed under strained (constant load or
      length) and unstrained conditions and imaged as whole nerve as well as plastic
      (methyl methacrylate) and paraffin embedded sections. These were tested for
      optimal excitation wavelength, quantitative image contrast, and overall quality.
      Root mean squared (RMS) contrast proved to be a reliable measure of the level of
      image contrast perceived by eye. We concluded that images obtained from tissue
      sections (plastic and paraffin) provided the most accurate and revealing SHG
      images of peripheral nerve structure. Removing the embedding material prior to
      imaging significantly improved image quality. Optimal excitation wavelengths were
      consistent regardless of the preparation method. 

PMID- 23962837
TI  - How clocks and hormones act in concert to control the timing of insect
      development.
AB  - During the last century, insect model systems have provided fascinating insights
      into the endocrinology and developmental biology of all animals. During the
      insect life cycle, molts and metamorphosis delineate transitions from one
      developmental stage to the next. In most insects, pulses of the steroid hormone
      ecdysone drive these developmental transitions by activating signaling cascades
      in target tissues. In holometabolous insects, ecdysone triggers metamorphosis,
      the remarkable remodeling of an immature larva into a sexually mature adult. The
      input from another developmental hormone, juvenile hormone (JH), is required to
      repress metamorphosis by promoting juvenile fates until the larva has acquired
      sufficient nutrients to survive metamorphosis. Ecdysone and JH act together as
      key endocrine timers to precisely control the onset of developmental transitions
      such as the molts, pupation, or eclosion. In this review, we will focus on the
      role of the endocrine system and the circadian clock, both individually and
      together, in temporally regulating insect development. Since this is not a
      coherent field, we will review recent developments that serve as examples to
      illuminate this complex topic. First, we will consider studies conducted in
      Rhodnius that revealed how circadian pathways exert temporal control over the
      production and release of ecdysone. We will then take a look at molecular and
      genetic data that revealed the presence of two circadian clocks, located in the
      brain and the prothoracic gland, that regulate eclosion rhythms in Drosophila. In
      this context, we will also review recent developments that examined how the
      ecdysone hierarchy delays the differentiation of the crustacean cardioactive
      peptide (CCAP) neurons, an event that is critical for the timing of ecdysis and
      eclosion. Finally, we will discuss some recent findings that transformed our
      understanding of JH function. 

PMID- 23962838
TI  - Nutrient signaling and developmental timing of maturation.
AB  - In animals, developmental timing of sexual maturation is tightly linked to
      nutrition and growth. Maturation only occurs once the juvenile has acquired
      sufficient nutrients and completed enough growth to produce a reproductively
      mature adult with a genetically predefined body size. Animals therefore adjust
      the duration of juvenile development to the dietary conditions. When nutrients
      are scarce the juvenile growth phase is extended to compensate for slow growth.
      Conversely, development is accelerated in nutrient rich environments where
      animals rapidly reach their genetic target size. To achieve such flexibility,
      nutrient-dependent growth regulators must feed into the endocrine system that
      controls the timing of maturation. Work on the fruit fly Drosophila has revealed
      a central role of secreted signal molecules with similarity to the conserved
      insulin-like growth factors (IGFs) in the decision making process. These
      molecules are involved in checkpoints that allow the endocrine system to decide
      whether to release the steroid hormone, ecdysone, that triggers maturation or
      extent development, depending on nutrient levels and growth status. Importantly,
      different dietary components influence timing of maturation in Drosophila, with
      proteins having the greatest impact; fat and sugar play a minor role, at least
      within the limits of what can be considered a balanced diet. Remarkably, excess
      dietary sugar concentrations that mimic physiological conditions associated with
      diabetes, negatively affect growth and delays maturation. Altogether, this shows
      that the source of energy in the diet is important for timing and may provide a
      paradigm for understanding the emerging links between diet, obesity and diabetes,
      and the onset of puberty. Here, we provide an overview of the system underlying
      developmental timing of maturation in Drosophila and review recent success in
      understanding its coupling to nutrition and growth. 

PMID- 23962840
TI  - MicroRNAs as components of systemic signaling pathways in Drosophila
      melanogaster.
AB  - MicroRNAs (miRNAs) ensure progression through development by synchronizing cell
      fate transitions in response to environmental cues. These cues are mediated at
      least in part by steroid hormones. Emerging evidence indicates that miRNAs are
      also components of additional systemic signaling pathways, including insulin,
      stress, immune, and circadian pathways. Thus, the roles that miRNAs play during
      development are reflected in their post-developmental functions, where they
      similarly function to coordinate cell behavior in response to environmental cues.
      In this review, we summarize current work highlighting the role of miRNAs in
      systemic signaling pathways in Drosophila melanogaster as a way of synthesizing
      the underlying roles of miRNAs in both animal developmental transitions and adult
      physiology. 

PMID- 23962839
TI  - Temporal patterning of neural progenitors in Drosophila.
AB  - Drosophila has recently become a powerful model system to understand the
      mechanisms of temporal patterning of neural progenitors called neuroblasts (NBs).
      Two different temporal sequences of transcription factors (TFs) have been found
      to be sequentially expressed in NBs of two different systems: the Hunchback,
      Kruppel, Pdm1/Pdm2, Castor, and Grainyhead sequence in the Drosophila ventral
      nerve cord; and the Homothorax, Klumpfuss, Eyeless, Sloppy-paired, Dichaete, and
      Tailless sequence that patterns medulla NBs. In addition, the intermediate neural
      progenitors of type II NB lineages are patterned by a different sequence:
      Dichaete, Grainyhead, and Eyeless. These three examples suggest that temporal
      patterning of neural precursors by sequences of TFs is a common theme to generate
      neural diversity. Cross-regulations, including negative feedback regulation and
      positive feedforward regulation among the temporal factors, can facilitate the
      progression of the sequence. However, there are many remaining questions to
      understand the mechanism of temporal transitions. The temporal sequence
      progression is intimately linked to the progressive restriction of NB competence,
      and eventually determines the end of neurogenesis. Temporal identity has to be
      integrated with spatial identity information, as well as with the Notch-dependent
      binary fate choices, in order to generate specific neuron fates. 

PMID- 23962842
TI  - Developmental transitions in C. elegans larval stages.
AB  - Molecular mechanisms control the timing, sequence, and synchrony of developmental
      events in multicellular organisms. In Caenorhabditis elegans, these mechanisms
      are revealed through the analysis of mutants with "heterochronic" defects: cell
      division or differentiation patterns that occur in the correct lineage, but
      simply at the wrong time. Subsets of cells in these mutants thus express temporal
      identities normally restricted to a different life stage. A seminal finding
      arising from studies of the heterochronic genes was the discovery of miRNAs;
      these tiny miRNAs are now a defining feature of the pathway. A series of
      sequentially expressed miRNAs guide larval transitions through stage-specific
      repression of key effector molecules. The wild-type lineage patterns are executed
      as discrete modules programmed between temporal borders imposed by the molting
      cycles. How these successive events are synchronized with the oscillatory molting
      cycle is just beginning to come to light. Progression through larval stages can
      be specifically, yet reversibly, halted in response to environmental cues,
      including nutrient availability. Here too, heterochronic genes and miRNAs play
      key roles. Remarkably, developmental arrest can, in some cases, either mask or
      reveal timing defects associated with mutations. In this chapter, we provide an
      overview of how the C. elegans heterochronic gene pathway guides developmental
      transitions during continuous and interrupted larval development. 

PMID- 23962841
TI  - Vegetative phase change and shoot maturation in plants.
AB  - As a plant shoot develops, it produces different types of leaves, buds, and
      internodes, and eventually acquires the capacity to produce structures involved
      in sexual reproduction. Morphological and anatomical traits that change in
      coordinated fashion at a predictable time in vegetative development allow this
      process to be divided into several more-or-less discrete phases; the transition
      between these phases is termed "vegetative phase change." Vegetative phase change
      is regulated by a decrease in the expression of the related microRNAs, miR156,
      and miR157, which act by repressing the expression of squamosa promoter binding
      protein/SBP-like (SBP/SPL) transcription factors. SBP/SPL proteins regulate a
      wide variety of processes in shoot development, including flowering time and
      inflorescence development. Answers to long-standing questions about the
      relationship between vegetative and reproductive maturation have come from
      genetic analyses of the transcriptional and posttranscriptional regulatory
      networks in which these proteins are involved. Studies conducted over several
      decades indicate that carbohydrates have a significant effect on phase-specific
      leaf traits, and recent research suggests that sugar may be the leaf signal that
      promotes vegetative phase change. 

PMID- 23962843
TI  - Steroid regulation of C. elegans diapause, developmental timing, and longevity.
AB  - Hormones play a critical role in driving major stage transitions and
      developmental timing events in many species. In the nematode C. elegans the
      steroid hormone receptor, DAF-12, works at the confluence of pathways regulating
      developmental timing, stage specification, and longevity. DAF-12 couples
      environmental and physiologic signals to life history regulation, and it is
      embedded in a rich architecture governing diverse processes. Here, we highlight
      the molecular insights, extraordinary circuitry, and signaling pathways governing
      life stage transitions in the worm and how they have yielded fundamental insights
      into steroid regulation of biological time. 

PMID- 23962844
TI  - Diapause: delaying the developmental clock in response to a changing environment.
AB  - Seasonal changes can induce organisms to modify their developmental growth. Many
      holometabolous insects, especially Lepidoptera, trigger diapause, an "actively
      induced" dormancy, for overwintering. Diapause is an alternative developmental
      pathway that reversibly blocks developmental growth during specific transitions
      and enhances the hibernating potential of the organism. Changes in environmental
      cues, such as light and temperature, trigger modifications in the levels, or in
      the timing, of developmental hormones. These in turn switch the developmental
      trajectory (diapause or direct development), strongly altering larval/pupal
      growth and inducing the appearance of diapause-bound seasonal morphs
      (polyphenism). We also discuss an example of vertebrate diapause using the
      killifish embryo as an example where diapause is an environmentally determined
      developmental switch analogous to that observed in lepidopteran dormancy. Based
      on the examples discussed here, we propose that the complex physiological
      responses leading to diapause might evolve quickly by relatively limited genetic
      changes in the regulation of hormonal signals that program normal developmental
      transitions. 

PMID- 23962845
TI  - Circannual transitions in gene expression: lessons from seasonal adaptations.
AB  - Circannual timing is important for the coordination of seasonal activities,
      particularly promoting the survival of individuals in adverse conditions through
      adaptive physiological and behavioral changes. This includes optimizing the
      survival of offspring by coordinating reproductive efforts at appropriate times.
      Thus, timing is very important for overall fitness. In this chapter, we provide
      several examples of circannually timed events, including mammalian hibernation,
      discussing the physiological changes that accompany these events, and some of the
      known genes and pathways underlying these changes. We then describe five
      candidate systems that are potentially involved in circannual timing. Finally, we
      discuss several recent advances in molecular biology and animal husbandry that
      have made the use of nonmodel organisms for research more feasible, which will
      hopefully promote and encourage further advancement in the knowledge of
      circannual timing. 

PMID- 23962848
TI  - Current Topics in Developmental Biology. Developmental timing. Preface.

PMID- 23962847
TI  - Keeping puberty on time: novel signals and mechanisms involved.
AB  - Puberty is the culmination of a complex series of maturational events that lead
      to the completion of sexual and somatic maturation and the acquisition of
      reproductive competence. This key developmental transition, which defines the
      boundary between immaturity and adulthood, is under the control of sophisticated
      regulatory networks that impinge upon the brain centers governing the
      reproductive axis. These networks are sensitive to earlier maturational events,
      such as brain sex differentiation, and dynamically regulated by a plethora of
      hormonal factors and environmental signals, which are essential for the fine
      tuning of the tempo of puberty. While much knowledge on mammalian puberty had
      been gleaned during the last decades, important recent developments have
      substantially expanded our understanding of the neuroendocrine and molecular
      mechanisms governing puberty onset. We will provide here a synoptic account of
      some of these important advancements, including the identification of the
      essential roles of hypothalamic kisspeptin signaling, and some of its putative
      partners, in pubertal maturation, the characterization of novel mechanisms
      involved in the metabolic regulation of puberty, and the recognition of the
      potential roles of epigenetics and miRNA-related pathways in the central control
      of puberty. It is expected that further progress in these and related areas will
      follow in the coming years. This will permit a better understanding of the
      physiological mechanisms responsible for pubertal timing and will help to
      decipher the pathophysiological basis for pubertal alterations in humans and
      wildlife species. 

PMID- 23962846
TI  - Unliganded thyroid hormone receptor regulates metamorphic timing via the
      recruitment of histone deacetylase complexes.
AB  - Anuran metamorphosis involves a complex series of tissue transformations that
      change an aquatic tadpole to a terrestrial frog and resembles the postembryonic
      perinatal period in mammals. Thyroid hormone (TH) plays a causative role in
      amphibian metamorphosis and its effect is mediated by TH receptors (TRs).
      Molecular analyses during Xenopus development have shown that unliganded TR
      recruits histone deacetylase (HDAC)-containing N-CoR/SMRT complexes and causes
      histone deacetylation at target genes while liganded TR leads to increased
      histone acetylations and altered histone methylations at target genes. Transgenic
      studies involving mutant TR-cofactors have shown that corepressor recruitment by
      unliganded TR is required to ensure proper timing of the onset of metamorphosis
      while coactivator levels influence the rate of metamorphic progression. In
      addition, a number of factors that can influence cellular free TH levels appear
      to contribute the timing of metamorphic transformations of different organs by
      regulating the levels of unliganded vs. liganded TR in an organ-specific manner.
      Thus, the recruitment of HDAC-containing corepressor complexes by unliganded TR
      likely controls both the timing of the initiation of metamorphosis and the
      temporal regulation of organ-specific transformations. Similar mechanisms likely
      mediate TR function in mammals as the maturation of many organs during
      postembryonic development is dependent upon TH and resembles organ metamorphosis
      in amphibians. 

PMID- 23962850
TI  - Numerical study of magnetic and pairing correlation in a bilayer triangular
      lattice.
AB  - By using the determinant Quantum Monte Carlo method, the magnetic and pairing
      correlation of the NaxCoO2?yH2O system are studied within the Hubbard model on a
      bilayer triangular lattice. The temperature dependence of the spin correlation
      function and pairing susceptibility with several kinds of symmetries at different
      electron fillings and interlayer coupling terms are investigated. It is found
      that the system shows antiferromagnetic correlation around half filling, and the
      fn-wave pairing correlation dominates over other kinds of pairing symmetry in the
      low doping region. As the electron filling decreases from half filling, both
      ferromagnetic correlation and the f-wave pairing susceptibility are enhanced and
      tend to dominate. It is also shown that both the magnetic susceptibility and
      pairing susceptibility decrease as the interlayer coupling increases. 

PMID- 23962849
TI  - Low-dose arsenic trioxide enhances 5-aminolevulinic acid-induced PpIX
      accumulation and efficacy of photodynamic therapy in human glioma.
AB  - Among glioma treatment strategies, 5-aminolevulinic acid (5-ALA)-based
      fluorescence-guided resection (FGR) and photodynamic therapy (PDT) have been used
      as effective novel approaches against malignant glioma. However, insufficient
      intracellular protoporphyrin IX (PpIX) accumulation limits the application of FGR
      and PDT in the marginal areas of gliomas. To overcome these issues, we assessed
      the intracellular levels of PpIX in human glioma cell lines and rat cortical
      astrocytes pretreated with 0.1MUM arsenic trioxide (ATO). Apoptosis and cell
      viability after PDT were evaluated using Annexin V-FITC apoptosis detection kit
      and MTT assay, respectively. In order to find out the possible mechanism, we
      investigated the expression of the key enzymes in the heme biosynthesis pathway,
      which regulates porphyrin synthesis in glioma cells. Our findings showed that the
      5-ALA-induced PpIX accumulation in glioma cell lines pretreated with 0.1MUM ATO
      was increased relative to the control groups. No changes in fluorescence
      intensity were detected in the rat cortical astrocytes pretreated using the same
      ATO concentration. Apoptosis following PDT in glioma cells pretreated with 0.1MUM
      ATO were significantly higher than in control groups, especially late apoptotic
      cells, while the cell viability was decreased. The expression of CPOX was
      upregulated in glioma cells after pretreatment with 0.1MUM ATO. We concluded that
      ATO was a potential optional approach in enhancing intracellular PpIX
      accumulation and improving the benefits of 5-ALA-induced FGR and PDT in glioma. 

PMID- 23962851
TI  - Is a rigid tricuspid annuloplasty ring superior to a flexible band when
      correcting secondary tricuspid regurgitation?
AB  - A best evidence topic in adult valvular surgery was written according to a
      structured protocol. The question addressed was 'Is a rigid tricuspid
      annuloplasty ring superior to a flexible band when correcting secondary tricuspid
      regurgitation (TR)?' A total of 166 papers were found using the reported search,
      of which, 13 presented the best evidence to answer the clinical question. The
      authors, country, journal, date of publication, patient group studied, study
      type, relevant outcomes and results of these papers are tabulated. All the 13
      papers were retrospective studies, from which 4 were case-control studies
      comparing the rigid ring annuloplasty approach with the flexible band technique,
      eight case series and one case report. From the first three case-control studies,
      we conclude that more progression to moderate-to-severe TR in the flexible band
      group than rigid ring group. However, the fourth paper reported that both rigid
      and flexible systems provide acceptable early tricuspid valve repair results, but
      the use of a rigid ring increases risk of subsequent ring dehiscence. Another
      rare complication about the rigid ring was described by Galinanes et al. We
      conclude that although there are relatively less risk of ring dehiscence or ring
      fracture in the flexible group, the rigid ring, particularly the new three
      dimensional MC3 ring, is inclined to be better than the flexible band in terms of
      a sustained effect for maintaining stable postoperative regurgitation grade
      according to the current available evidences. However, due to the limited
      controlled studies and their retrospective design, the results should be
      confirmed by prospective studies with a large number of patients. 

PMID- 23962852
TI  - Apicoaortic conduit and cerebral perfusion in mixed aortic valve disease: a
      computational analysis.
AB  - OBJECTIVES: The revival of the apicoaortic conduit has attracted new interest in
      this alternative treatment for severe aortic stenosis unsuitable for conventional
      valve replacement. However, doubts still exist about the perfusion of the
      epiaortic vessels after apicoaortic conduit implantation, especially when severe
      aortic stenosis is associated with aortic valve insufficiency. The aim of the
      study was to evaluate the perfusion of the epiaortic vessels (innominate artery,
      left carotid artery and left subclavian artery) in cases of mixed aortic valve
      disease before and after apicoaortic conduit implantation. METHODS: Starting from
      the data of a real patient with severe aortic stenosis and mild aortic
      insufficiency who underwent apicoaortic conduit implantation, we created a
      computational model where severe aortic valve stenosis was associated with
      different grades of aortic insufficiency (mild, medium and moderate). RESULTS: A
      total of six combinations were analysed. In all simulations, the more severe the
      concomitant aortic insufficiency, the more the flow through the epiaortic vessels
      was diminished. After apicoaortic conduit implantation, there was an absolute
      augmentation of the median output in each epiaortic vessel compared with the same
      combination of mixed aortic valve disease before implantation. Interestingly,
      retrograde flow from the conduit in the descending aorta was minimal and did not
      contribute to the improved output of the epiaortic vessels. CONCLUSIONS: The
      computational analysis suggested a protective effect, rather than steal
      phenomenon, of the apicoaortic conduit towards the cerebral perfusion, even in
      cases of mixed aortic valve disease.

PMID- 23962853
TI  - Isolated subpulmonic fibrous ring, mirror-image dextrocardia and situs solitus in
      a young lady unreported and a near miss.
AB  - Congenital diseases causing obstruction of the right ventricular outflow tract
      (RVOT) are common, but the isolated subpulmonary membrane/ring is extremely rare
      and can be difficult to diagnose precisely, especially in adults. We report a
      case of surgically resected isolated subpulmonic fibrous ring in a lady with
      mirror-image dextrocardia and abdominal situs solitus that was misdiagnosed by
      echocardiography as a subaortic membrane. 

PMID- 23962854
TI  - Coronary artery bypass grafting or percutaneous revascularization in acute
      myocardial infarction?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was as follows: is coronary artery bypass graft
      (CABG) surgery superior to percutaneous coronary intervention (PCI) in terms of
      in-hospital mortality and morbidity and long-term outcomes in patients with acute
      myocardial infarction (MI)? A total of 104 papers were returned using the
      selected search. Of these, six represented the best evidence to answer the
      clinical question. The selection criteria were comparative studies with only PCI
      and CABG groups in patients with acute MI. Case reports, reviews, recommendations
      and studies on a specific population or out of the context of acute MI were
      excluded. The authors, journal, date and country of publication, patient group
      studied, study type, relevant outcomes and results of these papers are tabulated.
      Almost all PCI patients received stents. One study used drug-eluting stents
      (DES). Two randomized studies showed similar short- and mid-term morbidities and
      mortalities in patients with acute MI in the PCI and CABG groups but higher
      repeat revascularization rates after PCI. Three observational studies found
      comparable survival, but one of them found more periprocedural events with CABG
      and the other two found more recurrent ischaemia requiring repeat
      revascularization in the PCI group. In one cohort study, CABG appeared to be an
      independent risk factor for death in N-STEMI according to the European
      Society/American College of Cardiology 2000 definition. The results are strongly
      influenced by the definition of acute MI. In an institution offering the two
      techniques with an equivalent accessibility, the principal advantage of PCI is a
      lower incidence of periprocedural and short-term morbidities. CABG, on the other
      hand, offers a better durability with less mid-term repeat revascularization
      required, especially when compared with PCI with DES implantation. Choice had to
      weight up coronary artery anatomy, number and localization of coronary artery
      stenosis and accessibility of both PCI and CABG treatments. Medical and surgical
      discussion within the Heart Team is required to make the best medical decision
      for each patient. 

PMID- 23962855
TI  - Blood and milk oxidative status after administration of different antioxidants
      during early postpartum in dairy cows.
AB  - This paper describes serum and milk oxidative profiles during early postpartum
      (10th-16th day) of dairy cows, after three different treatments: beta-carotene
      and alpha-tocopherol (Dalmavital(r), Fatro, Italy) (VAE Group); L-carnitine, d, L
      acetylmethionine, cyanocobalamin (Adiuxan(r), Ceva Vetem, Italy) (LCAR Group) and
      Dalmavital(r)+Adiuxan(r) (VAE/LCAR Group). Antioxidant administrations resulted
      in a general reduction in ROS concentrations which decreased more after a single
      drug administration (VAE and LCAR Groups) vitamin A and E serum levels increased
      in the three treated groups compared to control one (p < 0.05). Milk lipoperoxide
      content was statistically lower in treated cows than in control ones, whereas, as
      to vitamins, only vitamin E increased in all the treated groups compared to
      control. Taken together, the results of this study confirm the efficacy of
      antioxidant administration in the early postpartum of dairy cows and suggest that
      an excess in antioxidant administration may result, paradoxically, in an increase
      in ROS generation.

PMID- 23962856
TI  - Understanding the role of sulfur-thiamine interaction in the pathogenesis of
      sulfur-induced polioencephalomalacia in beef cattle.
AB  - This study examined the role of sulfur (S) in the pathogenesis of S-induced
      polioencephalomalacia (PEM) in beef cattle in the context of thiamine status and
      metabolism. Thiamine, thiamine monophosphate (TMP) and thiamine pyrophosphate
      (TPP) status in rumen fluid, blood and brain tissue were determined in beef
      heifers fed 2 levels of S [low S (LS) vs. high S (HS)] at 2 forage-to-concentrate
      ratios (F:C). High S diet did not affect ruminal and blood thiamine status.
      Interestingly, however, HS diet showed increased brain thiamine levels. No gross
      or histopathological changes indicative of PEM were detected in the brains of the
      heifers. Of note, during the course of the present study, we documented an
      outbreak of S-induced PEM in commercial feedlot steers. Brain thiamine variables
      in experimental animals fed HS diet were then contrasted with brain thiamine
      status in PEM affected feedlot steers. Interestingly, in clinically normal
      animals, exposure to HS diet resulted in increased levels of both TMP and TPP in
      the brain tissue, in comparison to animals fed LS diet. In contrast, the PEM
      affected brains showed overall lower levels of thiamine phosphates. It is
      noteworthy that TPP levels were 36.5% lower, despite 4.9-fold higher free
      thiamine in PEM brains compared to normal brains. Our results indicate that high
      dietary S may increase the metabolic demand for TPP, and that animals incapable
      of maintaining requisite levels of brain TPP are at high risk to develop
      fulminant cerebrocortical necrosis. 

PMID- 23962857
TI  - Cortisol levels in cats' hair in presence or absence of Microsporum canis
      infection.
AB  - The purpose of this work was to perform a preliminary screening in the domestic
      cat to assess the concentration of cortisol in hairs by radioimmunoassay
      technique (RIA) in presence or absence of Microsporum canis infections. A total
      of 245 cats (7 with cutaneous lesions referable to dermatophytosis and 238
      apparently healthy) coming from 14 shelters were examined. M. canis was isolated
      in 126 (51.4%) cats. The cortisol levels were significantly higher in cats with
      lesions or without lesions but with a high number of colonies in the plates (>=
      10 CFU) than in cats negative or with a lower number of colonies. The results
      obtained seem to highlight that chronic high levels of cortisol in cats could
      possibly promote the dermatophytes infections. Furthermore, in High-CFU
      asymptomatic cats, it could be present a state of infectious, and they,
      therefore, represents not a simple mechanical carrier.

PMID- 23962858
TI  - Role of implantable cardioverter-defibrillators in patients with continuous flow
      ventricular assist devices.

PMID- 23962859
TI  - Even cooler?!

PMID- 23962860
TI  - Unusual tachycardia-bradycardia syndrome during atrial fibrillation: what is the
      mechanism?

PMID- 23962861
TI  - Mapping and ablation of ventricular tachycardia from the left upper fascicle: how
      to make the most of the fascicular potential?

PMID- 23962862
TI  - Left atrial thrombus after appendage closure using LARIAT.

PMID- 23962863
TI  - Catheter ablation for persistent atrial fibrillation in a patient with previous
      repair of total anomalous pulmonary venous connection.

PMID- 23962864
TI  - Premature ventricular contraction-induced symptomatic slow pathway conduction
      successfully treated by catheter ablation.

PMID- 23962865
TI  - Conundrum of sudden cardiac death: making sense of missense.

PMID- 23962866
TI  - Catch me if you can: transseptal retrieval of a dislodged left atrial appendage
      occluder.

PMID- 23962867
TI  - Response to Letter by May et al regarding article, "Use of dabigatran for
      periprocedural anticoagulation in patients undergoing catheter ablation for
      atrial fibrillation" by Bassiouny et al.

PMID- 23962868
TI  - A systematic review on the effectiveness of school and community-based injury
      prevention programmes on risk behaviour and injury risk in 8-12 year old
      children.
AB  - OBJECTIVES: To review existing literature on the effectiveness of community-based
      and school-based physical activity related injury prevention programmes
      implemented to increase safety behaviour and decrease injury risk in 8-12 year
      old children, considering the methodological quality of the studies. DESIGN: A
      systematic review with quality assessment. METHODS: A systematic search was
      performed using the CINAHL, Cochrane, EMBASE, PubMed and Sportdiscus databases.
      Inclusion criteria included the following: children aged 8-12 years; school- or
      community-based injury prevention programmes; an outcome defined as number of
      injuries, injury incidence or safety behaviour; published in an English language
      journal. Methodological quality was assessed for all included studies. RESULTS:
      The search yielded 5377 records, of which 11 were included in the review; four
      studies were considered as being of high quality. The focus of studies that were
      included was on the use of safety devices (8), pedestrian safety (2) and physical
      activity-related injury prevention (1). For safety device use, short term effects
      of school- and community-based interventions are promising for 8-12 year olds.
      Results regarding sustainability of the effect are inconsistent. A mediating
      effect on the distribution of safety devices was observed. Both financial and non
      financial barriers seemed to prevent participants from purchasing a safety
      device. CONCLUSIONS: The short term effects for school- and community-based
      interventions using safety devices for 8-12 year olds are promising. More high
      quality research is, however warranted, preferably shifting focus from safety
      behaviour change to actual physical activity injury reduction.

PMID- 23962870
TI  - Comparison between open and arthroscopic-assisted foveal triangular
      fibrocartilage complex repair for post-traumatic distal radio-ulnar joint
      instability.
AB  - The aim of this study was to assess the objective and subjective functional
      outcomes after foveal reattachment of proximal or complete ulnar-sided triangular
      fibrocartilage complex lesions by two surgical procedures: an open technique or
      an arthroscopically assisted repair. The study was done prospectively on 49
      wrists affected by post-traumatic distal radio-ulnar joint instability. Twenty
      four patients were treated with the open technique (Group 1) and 25 by the
      arthroscopically assisted technique (Group 2). Magnetic resonance imaging
      demonstrated a clear foveal detachment of the triangular fibrocartilage complex
      in 67% of the cases. Arthroscopy showed a positive ulnar-sided detachment of the
      triangular fibrocartilage complex (positive hook test) in all cases. Distal radio
      ulnar joint stability was obtained in all but five patients at a mean follow-up
      of 6 months. Both groups had improvement of all parameters with significant
      differences in wrist pain scores, Mayo wrist score, Disability of the Arm,
      Shoulder and Hand questionnaire and Patient-Rated Wrist/Hand Evaluation
      questionnaire scores. There were no significant post-operative differences
      between the two groups in the outcome parameters except for the Disability of the
      Arm Shoulder and Hand questionnaire score, which was significantly better in
      Group 2 (p < 0.001). 

PMID- 23962871
TI  - The use of a pyrocarbon capitate resurfacing implant in chronic wrist disorders.
AB  - The present study describes the technique and results of proximal row carpectomy
      with resection of the head of the capitate and replacement with a pyrocarbon
      capitate resurfacing implant. The major indication for surgical treatment was
      arthritic changes on the head of the capitate. Patients were assessed by range of
      motion, grip strength, pain and functional scoring, and radiographic studies. In
      most patients, wrist function was improved and pain relief was obtained. This
      surgical procedure may represent a good alternative to total and partial wrist
      arthrodesis. 

PMID- 23962872
TI  - IFSSH Flexor Tendon Committee report 2014: from the IFSSH Flexor Tendon Committee
      (Chairman: Jin Bo Tang).
AB  - Hand surgeons continue to search for the best surgical flexor tendon repair and
      treatment of the tendon sheaths and pulleys, and they are attempting to establish
      postoperative regimens that fit diverse clinical needs. It is the purpose of this
      report to present the current views, methods, and suggestions of six senior hand
      surgeons from six different countries - all experienced in tendon repair and
      reconstruction. Although certainly there is common ground, the report presents
      provocative views and approaches. The report reflects an update in the views of
      the committee. We hope that it is helpful to surgeons and therapists in treating
      flexor tendon injuries. 

PMID- 23962874
TI  - Type 2 diabetes mellitus, glycemic control, and cancer risk.
AB  - Type 2 diabetes mellitus is characterized by prolonged hyperinsulinemia, insulin
      resistance, and progressive hyperglycemia. Disease management relies on glycemic
      control through diet, exercise, and pharmacological intervention. The goal of the
      present study was to examine the effects of glycemic control and the use of
      glucose-lowering medication on the risk of breast, prostate, and colon cancer.
      Patients diagnosed with type 2 diabetes mellitus (N=9486) between 1 January 1995
      and 31 December 2009 were identified and data on glycemic control (hemoglobin
      A1c, glucose), glucose-lowering medication use (insulin, metformin,
      sulfonylurea), age, BMI, date of diabetes diagnosis, insurance status,
      comorbidities, smoking history, location of residence, and cancer diagnoses were
      electronically abstracted. Cox proportional hazards regression modeling was used
      to examine the relationship between glycemic control, including medication use,
      and cancer risk. The results varied by cancer type and medication exposure. There
      was no association between glycemic control and breast or colon cancer; however,
      prostate cancer risk was significantly higher with better glycemic control
      (hemoglobin A1c <= 7.0%). Insulin use was associated with increased colon cancer
      incidence in women, but not with colon cancer in men or breast or prostate cancer
      risk. Metformin exposure was associated with reduced breast and prostate cancer
      incidence, but had no association with colon cancer risk. Sulfonylurea exposure
      was not associated with risk of any type of cancer. The data reported here
      support hyperinsulinemia, rather than hyperglycemia, as a major diabetes-related
      factor associated with increased risk of breast and colon cancer. In contrast,
      hyperglycemia appears to be protective in the case of prostate cancer.

PMID- 23962873
TI  - Nod2 deficiency is associated with an increased mucosal immunoregulatory response
      to commensal microorganisms.
AB  - On the basis of previous studies demonstrating that a breach of the colonic
      epithelial barrier is associated with a microbiota-dependent increase in lamina
      propria (LP) regulatory cells, we investigated if the lack of spontaneous
      intestinal inflammation observed in nucleotide-binding oligomerization domain 2
      (Nod2)-/- mice was due to enhanced intestinal regulatory function. We found that
      the LP CD4+ T-cell population of Nod2-/- mice contains an increased percentage of
      CD4+ regulatory T cells bearing transforming growth factor -beta/latency peptide
      (LP CD4+LAP (latency-associated peptide) + T cells) both under baseline
      conditions and following an intentional breach of the colonic barrier induced by
      ethanol administration. In addition, we found that Nod2-/- mice manifest
      decreased severity of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-colitis and that
      TNBS-colitis in Nod2-/- or Nod2+/+ mice is ameliorated by adoptive transfer of LP
      cells from ethanol-treated mice before, but not after, depletion of LAP+ T cells.
      This increased regulatory T-cell response in Nod2-/- mice could explain why NOD2
      polymorphisms in humans are not in themselves sufficient to establish
      inflammatory lesions. 

PMID- 23962875
TI  - Suberoylanilide hydroxamic acid (SAHA) causes tumor growth slowdown and triggers
      autophagy in glioblastoma stem cells.
AB  - Although suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor,
      has been used in clinical trials for cancer therapies, its pharmacological
      effects occur through a poorly understood mechanism. Here, we report that SAHA
      specifically triggers autophagy and reduces cell viability via promotion of
      apoptosis in the late phase of glioblastoma stem cells (GSCs). Using a cell line
      cultured from a glioblastoma biopsy, we investigated the properties and effects
      of GSCs under SAHA treatment in vitro. In vivo xenograft assays revealed that
      SAHA effectively caused tumor growth slowdown and the induction of autophagy.
      SAHA was sufficient to increase formation of intracellular acidic vesicle
      organelles, recruitment of LC3-II to the autophagosomes, potentiation of BECN1
      protein levels and reduced SQSTM1 levels. We determined that SAHA triggered
      autophagy through the downregulation of AKT-MTOR signaling, a major suppressive
      cascade of autophagy. Interestingly, upon depletion or pharmacological inhibition
      of autophagy, SAHA facilitates apoptosis and results in cell death at the early
      phase, suggesting that SAHA-induced autophagy functions probably act as a
      prosurvival mechanism. Furthermore, our results also indicated that the
      inhibition of SAHA-induced autophagy using chloroquine has synergistic effects
      that further increase apoptosis. Moreover, we found that a reduced dose of SAHA
      functioned as a potent modulator of differentiation and senescence. Taken
      together, our results provide a new perspective on the treatment of GSCs,
      indicating that SAHA is a promising agent for targeting GSCs through the
      induction of autophagy. 

PMID- 23962876
TI  - Ileal Crohn's disease with perforation misdiagnosed as ruptured appendicitis: a
      case report.

PMID- 23962877
TI  - Spikes in acute workload are associated with increased injury risk in elite
      cricket fast bowlers.
AB  - OBJECTIVE: To determine if the comparison of acute and chronic workload is
      associated with increased injury risk in elite cricket fast bowlers. METHODS:
      Data were collected from 28 fast bowlers who completed a total of 43 individual
      seasons over a 6-year period. Workloads were estimated by summarising the total
      number of balls bowled per week (external workload), and by multiplying the
      session rating of perceived exertion by the session duration (internal workload).
      One-week data (acute workload), together with 4-week rolling average data
      (chronic workload), were calculated for external and internal workloads. The size
      of the acute workload in relation to the chronic workload provided either a
      negative or positive training-stress balance. RESULTS: A negative training-stress
      balance was associated with an increased risk of injury in the week after
      exposure, for internal workload (relative risk (RR)=2.2 (CI 1.91 to 2.53),
      p=0.009), and external workload (RR=2.1 (CI 1.81 to 2.44), p=0.01). Fast bowlers
      with an internal workload training-stress balance of greater than 200% had a RR
      of injury of 4.5 (CI 3.43 to 5.90, p=0.009) compared with those with a training
      stress balance between 50% and 99%. Fast bowlers with an external workload
      training-stress balance of more than 200% had a RR of injury of 3.3 (CI 1.50 to
      7.25, p=0.033) in comparison to fast bowlers with an external workload training
      stress balance between 50% and 99%. CONCLUSIONS: These findings demonstrate that
      large increases in acute workload are associated with increased injury risk in
      elite cricket fast bowlers.

PMID- 23962878
TI  - Superior compliance with a neuromuscular training programme is associated with
      fewer ACL injuries and fewer acute knee injuries in female adolescent football
      players: secondary analysis of an RCT.
AB  - BACKGROUND: Little is known about the influence of compliance with neuromuscular
      training (NMT) on the knee injury rate in football. AIM: To evaluate team and
      player compliance with an NMT programme in adolescent female football and to
      study the association between compliance and acute knee injury rates. METHODS:
      Prospective cohort study based on a cluster randomised controlled trial on
      players aged 12-17 years with 184 intervention teams (2471 players) and 157
      control teams (2085 players). Exposure and acute time loss knee injuries were
      recorded. Team and player compliance was recorded by the coaches on a player
      attendance form. The intervention group was divided into tertiles of compliance.
      Injury rates were compared by calculating rate ratios (RRs) and 95% CIs using
      exact Poisson tests with the low-compliance tertile as reference. Seasonal
      compliance trends were analysed using linear regression. RESULTS: Players in the
      high-compliance tertile had an 88% reduction in the anterior cruciate ligament
      (ACL) injury rate (RR 0.12, 95% CI 0.01 to 0.85), whereas the rate in the control
      group players was not significantly different from those in the low-compliance
      tertile (RR 0.77, 95% CI 0.27 to 2.21). A significant deterioration occurred in
      team (b=-3.0% per month, 95% CI -5.2 to -0.8) and player (b=-5.0% per month, 95%
      CI -7.1 to -2.9) compliance over the season. CONCLUSIONS: Players with high
      compliance with the NMT programme had significantly reduced ACL injury rate
      compared with players with low compliance. Significant deterioration in team and
      player compliance occurred over the season.

PMID- 23962879
TI  - Thoracic injuries in professional rugby players: mechanisms of injury and imaging
      characteristics.
AB  - Professional rugby players are prone to traumatic thoracic injuries due to the
      use of minimal protective gear to cover the torso. In the 2007 Rugby World Cup,
      thoracic injuries occurred at a rate of 8.3 cases/1000 player-hours. CT and MRI
      play an important role in the diagnosis of these injuries. Vital internal organs,
      such as the heart, lungs, trachea, liver and large blood vessels lie within close
      proximity to the bony structures and what seems to be a simple rib fracture or
      clavicular dislocation can have potentially life-threatening complications that
      are not detected by conventional radiography. Cross-sectional imaging helps to
      determine the choice of treatment. Ultrasound offers a quick and dynamic imaging
      examination and allows high-resolution assessment of superficial tissues that
      complements conventional imaging. In this review article, we (1) presented data
      on incidence of thoracic injuries in professional rugby players; (2) described
      the anatomy of the joints comprising the thoracic cage and major muscles attached
      to the rib cage; (3) discussed indications and relevance for MRI and presented an
      optimised MRI protocol for assessment of suspected thoracic injury; and (4)
      illustrated various types of thoracic injuries seen in professional rugby
      players, including sternal contusion, retrosternal haematoma, manubriosternal
      disruption, sternoclavicular dislocation, rib fractures and injuries of the
      pectoralis major muscle. 

PMID- 23962880
TI  - The need for a novel approach to measure body composition: is ultrasound an
      answer?

PMID- 23962881
TI  - A versatile automated platform for micro-scale cell stimulation experiments.
AB  - Study of cells in culture (in vitro analysis) has provided important insight into
      complex biological systems. Conventional methods and equipment for in vitro
      analysis are well suited to study of large numbers of cells (>= 10(5)) in
      milliliter-scale volumes (>= 0.1 ml). However, there are many instances in which
      it is necessary or desirable to scale down culture size to reduce consumption of
      the cells of interest and/or reagents required for their culture, stimulation, or
      processing. Unfortunately, conventional approaches do not support precise and
      reproducible manipulation of micro-scale cultures, and the microfluidics-based
      automated systems currently available are too complex and specialized for routine
      use by most laboratories. To address this problem, we have developed a simple and
      versatile technology platform for automated culture, stimulation, and recovery of
      small populations of cells (100-2,000 cells) in micro-scale volumes (1-20 MUl).
      The platform consists of a set of fibronectin-coated microcapillaries ("cell
      perfusion chambers"), within which micro-scale cultures are established,
      maintained, and stimulated; a digital microfluidics (DMF) device outfitted with
      "transfer" microcapillaries ("central hub"), which routes cells and reagents to
      and from the perfusion chambers; a high-precision syringe pump, which powers
      transport of materials between the perfusion chambers and the central hub; and an
      electronic interface that provides control over transport of materials, which is
      coordinated and automated via pre-determined scripts. As an example, we used the
      platform to facilitate study of transcriptional responses elicited in immune
      cells upon challenge with bacteria. Use of the platform enabled us to reduce
      consumption of cells and reagents, minimize experiment-to-experiment variability,
      and re-direct hands-on labor. Given the advantages that it confers, as well as
      its accessibility and versatility, our platform should find use in a wide variety
      of laboratories and applications, and prove especially useful in facilitating
      analysis of cells and stimuli that are available in only limited quantities.

PMID- 23962882
TI  - Using chemical shift perturbation to characterise ligand binding.
AB  - Chemical shift perturbation (CSP, chemical shift mapping or complexation-induced
      changes in chemical shift, CIS) follows changes in the chemical shifts of a
      protein when a ligand is added, and uses these to determine the location of the
      binding site, the affinity of the ligand, and/or possibly the structure of the
      complex. A key factor in determining the appearance of spectra during a titration
      is the exchange rate between free and bound, or more specifically the off-rate
      koff. When koff is greater than the chemical shift difference between free and
      bound, which typically equates to an affinity Kd weaker than about 3MUM, then
      exchange is fast on the chemical shift timescale. Under these circumstances, the
      observed shift is the population-weighted average of free and bound, which allows
      Kd to be determined from measurement of peak positions, provided the measurements
      are made appropriately. (1)H shifts are influenced to a large extent by through
      space interactions, whereas (13)Calpha and (13)Cbeta shifts are influenced more
      by through-bond effects. (15)N and (13)C' shifts are influenced both by through
      bond and by through-space (hydrogen bonding) interactions. For determining the
      location of a bound ligand on the basis of shift change, the most appropriate
      method is therefore usually to measure (15)N HSQC spectra, calculate the
      geometrical distance moved by the peak, weighting (15)N shifts by a factor of
      about 0.14 compared to (1)H shifts, and select those residues for which the
      weighted shift change is larger than the standard deviation of the shift for all
      residues. Other methods are discussed, in particular the measurement of (13)CH3
      signals. Slow to intermediate exchange rates lead to line broadening, and make Kd
      values very difficult to obtain. There is no good way to distinguish changes in
      chemical shift due to direct binding of the ligand from changes in chemical shift
      due to allosteric change. Ligand binding at multiple sites can often be
      characterised, by simultaneous fitting of many measured shift changes, or more
      simply by adding substoichiometric amounts of ligand. The chemical shift changes
      can be used as restraints for docking ligand onto protein. By use of quantitative
      calculations of ligand-induced chemical shift changes, it is becoming possible to
      determine not just the position but also the orientation of ligands. 

PMID- 23962883
TI  - Long-range proton-carbon coupling constants: NMR methods and applications.
AB  - A general review of novel NMR methods to measure heteronuclear long-range proton
      carbon coupling constants ((n)JCH; n>1) in small molecules is made. NMR
      experiments are classified in terms of NMR pulse scheme and cross-peak nature. A
      discussion about simplicity, general applicability and accuracy for each
      particular NMR experiment is presented and exemplified. Important aspects such as
      the sign determination and measurement of very small coupling values involving
      protonated and non-protonated carbons as well as the complementarity between
      different experiments are also discussed. Finally, a compilation of applications
      in structural and conformational analysis of different types of molecules since
      2000 is surveyed. 

PMID- 23962884
TI  - Whole body fat: content and distribution.
AB  - Obesity and its co-morbidities, including type II diabetes, insulin resistance
      and cardiovascular diseases, have become one of the biggest health issues of
      present times. The impact of obesity goes well beyond the individual and is so
      far-reaching that, if it continues unabated, it will cause havoc with the
      economies of most countries. In order to be able to fully understand the
      relationship between increased adiposity (obesity) and its co-morbidity, it has
      been necessary to develop proper methodology to accurately and reproducibly
      determine both body fat content and distribution, including ectopic fat depots.
      Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) have recently emerged as
      the gold-standard for accomplishing this task. Here, we will review the use of
      different MRI techniques currently being used to determine body fat content and
      distribution. We also discuss the pros and cons of MRS to determine ectopic fat
      depots in liver, muscle, pancreas and heart and compare these to emerging MRI
      techniques currently being put forward to create ectopic fat maps. Finally, we
      will discuss how MRI/MRS techniques are helping in changing the perception of
      what is healthy and what is normal and desirable body-fat content and
      distribution. 

PMID- 23962885
TI  - Smart multifunctional fluids for lithium ion batteries: enhanced rate performance
      and intrinsic mechanical protection.
AB  - Lithium ion batteries are attractive power sources for the consumer electronics
      market and are being aggressively developed for road transportation.
      Nevertheless, issues with safety and reliability need to be solved prior to the
      large-scale uptake of these batteries. There have recently been significant
      development and assessment of materials with resistance to mechanical abuse, with
      the aims of reinforcing the battery and preventing puncturing during a crash.
      Most of the work on battery mechanical safety has concentrated on the external
      packaging of batteries, with little attention being paid to the enclosed
      electrolyte. We report on smart multifunctional fluids that act as both highly
      conductive electrolytes and intrinsic mechanical protectors for lithium ion
      batteries. These fluids exhibit a shear thickening effect under pressure or
      impact and thus demonstrate excellent resistance to crushing. Also, the fluids
      show higher ionic conductivities and comparable redox stability windows to the
      commercial liquid electrolytes. 

PMID- 23962886
TI  - Long-term clinical outcomes of statin use for chronic heart failure: a meta
      analysis of 15 prospective studies.
AB  - BACKGROUND: The effect of statin treatment on the long-term prognosis in patients
      with chronic heart failure (CHF) remains uncertain. This study aimed to answer
      the question by a meta-analysis. METHODS: The Cochrane databases, MEDLINE and
      EMBASE, were systematically searched. The eligibility of prospective studies that
      assigned CHF patients to receive statin treatment and a control (no statin
      treatment), had defined prognostic outcomes as primary endpoint, and had a
      minimal follow-up of 12 months was determined. RESULTS: Fifteen studies involving
      45,110 patients were included in the analysis. Additional statin treatment was
      associated with reduced all-cause mortality (risk ratios [RR] = 0.71, 95%
      confidence intervals [CI] 0.61-0.83) and reduced rehospitalisation rate for heart
      failure (RR = 0.84, 95% CI 0.74-0.96). Statin treatment, however, had little
      impact on pump failure mortality, cardiovascular mortality, and sudden cardiac
      death. Atorvastatin treatment appeared to facilitate to reduce all-cause
      mortality (lnRR = 0.61, p = 0.05) and rehospitalisation for heart failure (lnRR =
      0.44, p = 0.04) compared with non-atorvastatin therapy. CONCLUSIONS: Based on the
      available data, statins persistently decreased all-cause mortality and the
      incidence of rehospitalisation for heart failure in CHF patients, and the
      benefits might be partially associated with use of specific statin.

PMID- 23962887
TI  - Epidural extension of infected chest wall haematoma and empyema causing spinal
      cord compression.
AB  - We report a case of thoracic epidural extension of an infected extra-pleural and
      chest wall haematoma with evidence of spinal cord compression and signs of cauda
      equina. Emergency spinal cord decompression with laminectomy followed by
      thoracotomy was performed. 

PMID- 23962888
TI  - Bright muscle, weak heart, bad start?

PMID- 23962889
TI  - Long term follow-up after aortic valve replacement (Ross procedure):
      echocardiographic determinants of ventricular recovery.
AB  - AIMS AND METHODS: This prospective cohort study aimed to assess LV recovery post
      aortic valve replacement, stratified according to pre-operative valve lesion
      (aortic stenosis (AS), mixed disease (AS/AR) or aortic regurgitation (AR)), as
      well as define predictors of persistent LV dilatation post operation. We
      prospectively followed all patients post Ross procedure performed between 1992
      and 2009 by a single surgeon. Echocardiography was performed pre-operatively, at
      approximately one year post operation then second yearly thereafter. RESULTS: 265
      patients were followed for a mean of 6.4 years (range 1-14 years, total 1702
      patient-years). Seventy percent were male and mean age was 38.8 +/- 12.6 years.
      The indication for surgery was AS in 44.5% (118), AS/AR in 23.4% (62), and AR in
      32.1% (85). Overall mortality was 1.8% and 80% of deaths were non-cardiac.
      Morbidity was low and the need for pacing was less than 1%. Ninety-nine percent
      of patients were NYHA class 1 at one year follow up. The indexed LV end diastolic
      diameter (LVEDDi) decreased significantly post-operation in the AR (3.34 +/- 0.39
      2.66 +/- 0.32 cm/m(2), p<0.001) and mixed (2.85 +/- 0.38-2.65 +/- 0.30 cm/m(2), p
      = 0.01) groups, whilst the indexed systolic LV dimension decreased significantly
      post-operation in the AR group (2.26 +/- 0.34-1.87 +/- 0.27, p<0.001). At five
      years post operation, independent predictors for a larger LVEDDi were female
      gender, a pre-operative LVEDDi >3.0 cm/m(2) and the presence of mild aortic
      regurgitation at one year post-operation. Pre-operative valve lesion was not a
      predictor. The only independent predictor of a lesser reduction of LVEDDi at five
      year follow-up was mild post-operative AR, whilst predictors of a lesser
      reduction in indexed left ventricular end systolic diameter (LVESDi) at five year
      follow-up included mild post-operative AR and a larger pre-operative LVEDDi. LV
      wall thickness decreased significantly the AS and AS/AR groups within one year
      post operation, whilst the neo-aortic root size remained stable throughout follow
      up. CONCLUSIONS: Recovery of LV size post Ross procedure is influenced
      predominantly by the pre-operative LV size, in particular the indexed LV end
      diastolic diameter. The pre-operative valve lesion was not predictive of larger
      ventricular dimensions post AVR, but independent predictors of a larger
      ventricular dimensions post operation included female gender, enlarged pre
      operative LVEDDi and the presence of mild AR in the first post operative year.
      Those with mild post-operative AR did not have progressive LV enlargement, thus
      the clinical significance of this finding remains unclear.

PMID- 23962890
TI  - Resistance training during pregnancy and perinatal outcomes.
AB  - BACKGROUND: Approximately 10% of women engage in resistance training during
      pregnancy; however there is limited research on this activity. The purpose of
      this study was to examine associations between resistance training and adverse
      outcomes. METHODS: Women completed an online survey and recalled their exercise
      habits during each trimester of their most recent pregnancy within the previous 5
      years. Women also reported pregnancy and birth outcomes. Participants were then
      categorized into 3 groups based on leisure-time exercise: 1) Resistance + aerobic
      training (RTAE), 2) Aerobic exercise only (AE), and 3) no exercise (NE). RESULTS:
      284 women completed the survey. Women in the RTAE group resistance trained on
      average 2.9 days/ week for 27.3 minutes/session. The prevalences of hypertensive
      disorders (HD) and gestational diabetes mellitus (GDM) were significantly lower
      in the RTAE group when compared with the grouping of AE + NE women. Prepregnancy
      body mass index (BMI) was the strongest factor related to both GDM and HD. There
      was no difference in the risk of preterm labor, mode of delivery, or gestational
      age at delivery by exercise status. CONCLUSIONS: Our results suggest that women
      can safely engage in aerobic exercise and resistance training for muscular
      endurance 3 days/week for 30 minutes throughout gestation.

PMID- 23962893
TI  - A new approach to mirror neurons: developmental history, system-level theory and
      intervention experiments.

PMID- 23962894
TI  - How does "mirroring" support joint action?

PMID- 23962895
TI  - Studying mirror mechanisms within generative and predictive architectures for
      joint action.

PMID- 23962891
TI  - Impaired cerebellar-dependent eyeblink conditioning in first-degree relatives of
      individuals with schizophrenia.
AB  - Consistent with reports of cerebellar structural, functional, and neurochemical
      anomalies in schizophrenia, robust cerebellar-dependent delay eyeblink
      conditioning (dEBC) deficits have been observed in the disorder. Impaired dEBC is
      also present in schizotypal personality disorder, an intermediate phenotype of
      schizophrenia. The present work sought to determine whether dEBC deficits exist
      in nonpsychotic first-degree relatives of individuals with schizophrenia. A
      single-cue tone dEBC paradigm consisting of 10 blocks with 10 trials each (9
      paired and 1 unpaired trials) was used to examine the functional integrity of
      cerebellar circuitry in schizophrenia participants, individuals with a first
      degree relative diagnosed with schizophrenia, and healthy controls with no first
      degree relatives diagnosed with schizophrenia. The conditioned stimulus (a 400ms
      tone) coterminated with the unconditioned stimulus (a 50ms air puff to the left
      eye) on paired trials. One relative and 2 healthy controls were removed from
      further analysis due to declining conditioned response rates, leaving 18
      schizophrenia participants, 17 first-degree relatives, and 16 healthy controls.
      Electromyographic data were subsequently analyzed using growth curve models in
      hierarchical linear regression. Acquisition of dEBC conditioned responses was
      significantly impaired in schizophrenia and first-degree relative groups compared
      with controls. This finding that cerebellar-mediated associative learning
      deficits are present in first-degree relatives of individuals with schizophrenia
      provides evidence that dEBC abnormalities in schizophrenia may not be due to
      medication or course of illness effects. Instead, the present results are
      consistent with models of schizophrenia positing cerebellar-cortical circuit
      abnormalities and suggest that cerebellar abnormalities represent a risk marker
      for the disorder. 

PMID- 23962892
TI  - Computational design of protein-small molecule interfaces.
AB  - The computational design of proteins that bind small molecule ligands is one of
      the unsolved challenges in protein engineering. It is complicated by the
      relatively small size of the ligand which limits the number of intermolecular
      interactions. Furthermore, near-perfect geometries between interacting partners
      are required to achieve high binding affinities. For apolar, rigid small
      molecules the interactions are dominated by short-range van der Waals forces. As
      the number of polar groups in the ligand increases, hydrogen bonds, salt bridges,
      cation-pi, and pi-pi interactions gain importance. These partial covalent
      interactions are longer ranged, and additionally, their strength depends on the
      environment (e.g. solvent exposure). To assess the current state of protein-small
      molecule interface design, we benchmark the popular computer algorithm Rosetta on
      a diverse set of 43 protein-ligand complexes. On average, we achieve sequence
      recoveries in the binding site of 59% when the ligand is allowed limited
      reorientation, and 48% when the ligand is allowed full reorientation. When
      simulating the redesign of a protein binding site, sequence recovery among
      residues that contribute most to binding was 52% when slight ligand reorientation
      was allowed, and 27% when full ligand reorientation was allowed. As expected,
      sequence recovery correlates with ligand displacement. 

PMID- 23962896
TI  - Efficacy and safety of natalizumab in Crohn's disease patients treated at 6
      Boston academic hospitals.
AB  - BACKGROUND: Despite trials demonstrating its efficacy, many physicians harbor
      concerns regarding the use of natalizumab in the treatment of patients with
      refractory Crohn's disease (CD). The purpose of this study was to perform a
      descriptive analysis of a series of CD patients not currently enrolled in a
      clinical trial. METHODS: A retrospective case review of patients treated with
      natalizumab at 6 sites in Massachusetts: Boston Medical Center, Beth Israel
      Deaconess Medical Center, Brigham & Women's Hospital, Lahey Clinic, Massachusetts
      General Hospital, and UMass Medical Center. RESULTS: Data on 69 CD patients on
      natalizumab were collected. At the start of treatment, patients' disease duration
      was 12 years. A high proportion of patients were women (68%), presented with
      perianal disease (65%) and upper gastrointestinal tract involvement (14%). Prior
      nonbiologic therapies were steroids (96%), thiopurines (94%), antibiotics (74%),
      methotrexate (58%), and at least two anti-tumor necrosis factor agent failures
      (81%). Sixty-nine percent (44 of 64 patients) with available medical evaluation
      had a partial or complete clinical response. Loss of response was 13% after an
      average of 1 year of treatment. Adverse events were infusion reactions,
      headaches, fever, and infections. No case of progressive multifocal
      leukoencephalopathy was observed. CONCLUSIONS: In our clinical experience outside
      the context of a clinical trial, natalizumab is largely reserved for CD patients
      with extensive ileocolonic disease who have failed conventional
      immunosuppressants and of at least 2 anti-tumor necrosis factor agents. This drug
      is, however, well tolerated and offers significant clinical improvement for more
      than a year in one-third of these difficult-to-treat CD patients.

PMID- 23962897
TI  - Iron deficiency generates secondary thrombocytosis and platelet activation in
      inflammatory bowel disease : the randomized, controlled ThromboVIT trial.

PMID- 23962898
TI  - Reply to Zuo et al.

PMID- 23962899
TI  - NMR spectroscopy with force-gradient detection on a GaAs epitaxial layer.
AB  - We demonstrate nuclear magnetic resonance spectroscopy on 35 MUm(3) of (69)Ga in
      a GaAs epitaxial layer in vacuum at 5K, and 5T yielding a linewidth on the order
      of 10 kHz. This was achieved by a force-gradient magnetic resonance detection
      scheme, using the interaction between the force-gradient of a Ni sphere-tipped
      single crystal Si cantilever and the nuclear spins to register changes in the
      spin state as a change in the driven cantilever's natural resonant frequency. The
      dichotomy between the background magnetic field (B0) homogeneity requirements
      imposed by NMR spectroscopy and the magnetic particle's large magnetic field
      gradient is resolved via sample shuttling during the NMR pulse encoding. A GaAs
      sample is polarized in a B0 of 5T for 3 T1. The sample is shuttled away from the
      magnetic particle to a region of negligible magnetic field inhomogeneity. A
      (pi/2)x pulse rotates the polarization to the xy-plane, the magnetization is
      allowed to precess for 2-200 MUs before a (pi/2)x or (pi/2)y pulse stores the
      remaining spin along the z-axis that represents a single point of the free
      induction decay (FID). The sample is shuttled back to the established tip-sample
      distance. An adiabatic rapid passage (ARP) sweep inverts the spins in a volume of
      interest, causing the cantilever's natural resonance frequency to shift an amount
      proportional to the spin polarization in the volume. By varying the delay between
      the first and second (pi/2) pulses the entire FID is measured.

PMID- 23962900
TI  - Acacetin and chrysin, two polyphenolic compounds, alleviate telomeric position
      effect in human cells.
AB  - We took advantage of the ability of human telomeres to silence neighboring genes
      (telomere position effect or TPE) to design a high-throughput screening assay for
      drugs altering telomeres. We identified, for the first time, that two dietary
      flavones, acacetin and chrysin, are able to specifically alleviate TPE in human
      cells. We further investigated their influence on telomere integrity and showed
      that both drugs drastically deprotect telomeres against DNA damage response.
      However, telomere deprotection triggered by shelterin dysfunction does not affect
      TPE, indicating that acacetin and chrysin target several functions of telomeres.
      These results show that TPE-based screening assays represent valuable methods to
      discover new compounds targeting telomeres.Molecular Therapy-Nucleic Acids (2013)
      2, e116; doi:10.1038/mtna.2013.42; published online 20 August 2013. 

PMID- 23962901
TI  - A temperature dependent tunneling study of the spin density wave gap in EuFe2As2
      single crystals.
AB  - We report temperature dependent scanning tunneling microscopy and spectroscopy
      measurements on single crystals of EuFe2As2 in the 15-292 K temperature range.
      The in situ cleaved crystals show atomic terraces with homogeneous tunnel spectra
      that correlate well with the spin density wave (SDW) transition at a temperature,
      TSDW ~ 186 K. Above TSDW the local tunnel spectra show a small depression in the
      density of states (DOS) near the Fermi energy (EF). The gap becomes more
      pronounced upon entering the SDW state with a gap value ~90 meV at 15 K. However,
      the zero bias conductance remains finite down to 15 K indicating a finite DOS at
      the EF in the SDW phase. Furthermore, no noticeable change is observed in the DOS
      at the antiferromagnetic ordering transition of Eu(2+) moments at 19 K. 

PMID- 23962902
TI  - Platinum compounds in children with cancer: toxicity and clinical management.
AB  - Platinum compounds are widely used in the treatment of pediatric tumors such as
      neuroblastoma, germ-cell tumors, osteosarcoma, retinoblastoma, hepatoblastoma,
      brain tumors (low-grade gliomas and medulloblastoma/PNET), and relapsed and
      refractory lymphomas. The three major platinum compounds (cisplatin, carboplatin,
      and oxaliplatin) have a similar pharmacokinetics profile and mechanism of action,
      but the differences in their chemical structure are responsible for their
      different antitumor activity and toxicity. In this review, we have described the
      main characteristics of cisplatin, carboplatin, and oxaliplatin, focusing on
      their toxic effects and possible strategies to prevent them to improve the
      clinical outcomes in pediatric cancer patients. The underlying mechanism of each
      platinum-related toxicity is shown together with the clinical manifestations.
      Furthermore, possible preventive strategies are suggested to reduce the negative
      impact of platinum compounds on the quality of life of children with cancer.
      Cisplatin seems to be mostly ototoxic and nephrotoxic, carboplatin mainly
      produces myelosuppression, whereas oxaliplatin induces predominantly peripheral
      sensory neurotoxicity. In contrast, nausea and vomiting can be linked to all
      platinum compounds, although cisplatin exerts the strongest emetic effect. A
      correct knowledge of pharmacokinetics and toxicological profile of platinum
      compounds may aid physicians prevent their toxicity on auditory, nervous, renal,
      and bone marrow function, improving the quality of life of pediatric cancer
      patients.

PMID- 23962903
TI  - Salvage intracerebrospinal fluid thiotepa in breast cancer-related leptomeningeal
      metastases: a retrospective case series.
AB  - There is currently a paucity of data on salvage intracerebrospinal fluid (intra
      CSF) chemotherapy in leptomeningeal metastases (LM). This report is a single
      institution experience with salvage treatment in patients with breast cancer (BC)
      and LM. This retrospective cohort describes 24 consecutive patients with BC
      selected for a second-line of treatment for LM. The first line of LM treatment
      consisted of intra-CSF liposomal cytarabine in all patients combined with
      systemic therapy in 18 cases and radiotherapy in four cases. Second-line
      (salvage) treatment utilized intra-CSF thiotepa in all and systemic chemotherapy
      in nine patients. No patient received CNS-directed radiotherapy. The median
      Eastern Cooperative Oncology Group performance status at initiation of intra-CSF
      thiotepa treatment was 3 (range 1-4). The median progression-free survival and
      median survival following intra-CSF thiotepa was 3.1 months (range 3 days-2
      years) and 4.0 months (range 6 days-2.5 years), respectively. The median overall
      survival from LM diagnosis was 9.5 months (range 1.3 months-2.7 years). No grade
      3 or higher toxicity was observed. Recognizing the limits of a retrospective
      study, intra-CSF thiotepa has an acceptable toxicity profile and appears to be a
      reasonable option for selected BC patients.

PMID- 23962904
TI  - Phase I dose escalation study of the PKCiota inhibitor aurothiomalate for
      advanced non-small-cell lung cancer, ovarian cancer, and pancreatic cancer.
AB  - Protein kinase C iota (PKCiota) is overexpressed in non-small-cell lung cancer,
      ovarian, and pancreatic cancers, where it plays a critical role in oncogenesis.
      The gold compound aurothiomalate (ATM) has been shown to inhibit PKCiota
      signaling and exerts potent antitumor activity in preclinical models. We sought
      to determine the maximum tolerated dose (MTD) of ATM. We conducted a phase I dose
      escalation trial of ATM in patients with non-small-cell lung cancer, ovarian or
      pancreatic cancer. Patients received ATM intramuscularly weekly for three cycles
      (cycle duration 4 weeks) at 25, 50, or 75 mg in a 3+3 design. The dose was not
      escalated for individual patients. Blood samples were analyzed for elemental gold
      levels. Patients were evaluated every 4 weeks for toxicity and every 8 weeks for
      response. Fifteen patients were enrolled in this study. Six patients were treated
      at 25 mg, seven at 50 mg, and two at 75 mg. There was one dose-limiting toxicity
      at 25 mg (hypokalemia), one at 50 mg (urinary tract infection), and none at 75
      mg. There were three grade 3 hematologic toxicities. The recommended MTD of ATM
      is 50 mg. Patients received treatment for a median of two cycles (range 1-3).
      There appeared to be a dose-related accumulation of steady-state plasma
      concentrations of gold consistent with linear pharmacokinetics. In summary, this
      phase I study was successful in identifying ATM 50 mg intramuscularly weekly as
      the MTD. Future clinical investigations targeting PKCiota are currently in
      progress.

PMID- 23962905
TI  - Crizotinib overcomes hepatocyte growth factor-mediated resistance to gefitinib in
      EGFR-mutant non-small-cell lung cancer cells.
AB  - Acquired resistance develops ultimately in most non-small-cell lung cancer
      patients with epidermal growth factor receptor (EGFR) mutations who initially
      respond to EGFR tyrosine kinase inhibitors. Overexpression of hepatocyte growth
      factor (HGF) contributes to a considerable part of acquired resistance.
      Therefore, novel approaches are required for better management to overcome the
      resistance. Here, we tested whether crizotinib (PF02341066), a MET kinase
      inhibitor, can overcome two different HGF-triggered mechanisms of resistance to
      gefitinib in human EGFR mutant lung cancer cell lines HCC827 and PC-9. Compared
      with the monotherapy, the combined treatment of crizotinib and gefitinib induced
      apoptosis and significantly inhibited the growth of cells in the presence of HGF
      by blocking the MET/PI3K/Akt pathway. Further, we demonstrated that crizotinib
      plus gefitinib successfully prevented the emergence of gefitinib-resistant HCC827
      cells induced by transient exposure to HGF. In vivo, the combination therapy with
      crizotinib and gefitinib also markedly suppressed the growth of gefitinib
      resistant mouse xenografts established by injecting HCC827 cells mixed with HGF
      producing fibroblasts (MRC-5 cells) subcutaneously into severe combined
      immunodeficient mice. In conclusion, these findings provided preclinical evidence
      that crizotinib can be used in the treatment of HGF-induced resistance to
      gefitinib in EGFR mutant lung cancer. 

PMID- 23962906
TI  - Nanocrystalline anatase TiO2: a new anode material for rechargeable sodium ion
      batteries.
AB  - Anatase TiO2 nanocrystals were successfully employed as anodes for rechargeable
      Na-ion batteries for the first time. The mesoporous electrodes exhibited a highly
      stable reversible charge storage capacity of ~150 mA h g(-1) over 100 cycles, and
      were able to withstand high rate cycling, fully recovering this capacity after
      being cycled at rates as high as 2 A g(-1).

PMID- 23962907
TI  - ERCC1 C8092A (rs3212986) polymorphism as a predictive marker in esophageal cancer
      patients treated with cisplatin/5-FU-based neoadjuvant therapy.
AB  - OBJECTIVE: At present, no consensus exists on the beneficial effect of
      preoperative cisplatin/5-fluorouracil (5-FU)-based chemotherapy versus primary
      surgery in the management of patients with esophageal cancer. The aim of this
      study was to evaluate the impact of some relevant genetic polymorphisms, within
      drug-related and DNA repair genes, on the clinical outcome of esophageal cancer
      patients subjected to cisplatin/5-FU-based neoadjuvant treatment. METHODS: DNA
      from 143 esophageal cancer patients, 63 receiving neoadjuvant therapy and 80
      receiving primary surgery, was analyzed for the following polymorphisms: the
      GSTM1 null, GSTT1 null, and GSTP1 Ile105Val (rs16953) in glutathione S
      transferase (GST) family, 2 in thymidylate synthase (TS) gene, and the ERCC1
      Asn118Asn (rs11615), ERCC1 C8092A (rs3212986), XPD/ERCC2 Asp312Asn (rs1799793),
      and XPD/ERCC2 Lys751Gln (rs13181) of the nucleotide excision repair pathway.
      RESULTS: We found that the ERCC1 rs3212986, although not associated with
      therapeutic response, is an independent predictive marker of better outcome in a
      cisplatin/5-FU-based neoadjuvant setting (hazard ratio: 0.38, 95% confidence
      interval: 0.2-0.73, P=0.008). In contrast, no association with clinical outcome
      was observed for this polymorphism in the primary surgery group. CONCLUSION: Our
      study indicates the ERCC1 rs3212986 as a predictive marker in the cisplatin/5-FU
      based neoadjuvant setting, and also suggests its use as a marker to select the
      appropriate therapeutic approach in esophageal cancer patients.

PMID- 23962908
TI  - PharmGKB summary: tamoxifen pathway, pharmacokinetics.

PMID- 23962909
TI  - Severe toxicity and polymerase-gamma gene abnormalities in Malawian adults on
      stavudine-based antiretroviral therapy.
AB  - In a cohort study of Malawian adults who were followed up through their second
      year of stavudine-containing antiretroviral therapy, we sequenced the polymerase
      gamma gene (POLG) of 10 of the 14 patients with the most severe stavudine side
      effects. No mutations were observed, suggesting that monogenic POLG mutations are
      not a common pathogenic determinant of severe stavudine-associated mitochondrial
      toxicity in Malawians. 

PMID- 23962910
TI  - PharmGKB summary: very important pharmacogene information for the epidermal
      growth factor receptor.

PMID- 23962912
TI  - Initial linkage and subsequent retention in HIV care for a newly diagnosed HIV
      infected cohort in Denver, Colorado.
AB  - This is a retrospective cohort study of 352 newly diagnosed HIV-infected
      individuals in Denver, from 2005 to 2007. Utilizing data from 3 health care
      systems, 2 clinical trials units, and statewide Colorado HIV laboratory reporting
      databases, we tracked initial linkage to HIV care, retention in care, loss to
      follow-up, and transitions between HIV care providers. After more than 2.6 years
      of follow-up, 256 (73%) individuals linked to HIV care within 180 days. Of the
      301 individuals who eventually linked to care, 168 (56%) had at least one 180-day
      gap in care, while 49 (16%) had a 360-day gap. Transitions in care were common,
      with 131 (37%) individuals accessing care from 2 different providers and 15%
      having evidence of living outside of Colorado. In this newly diagnosed HIV
      infected cohort, linkage to care was slow and long-term retention in care was
      poor. Transitions between HIV care providers were common and may impair
      engagement in care over time. Out-of-state migration was frequent and may cause
      an underestimation of engagement in care. 

PMID- 23962913
TI  - Clinical presentation and outcome of toxoplasma encephalitis in HIV-infected
      patients from Zaria, Northern Nigeria: a case series of 9 patients.
AB  - Toxoplasma encephalitis (TE) is the most common cause of focal deficits in
      patients living with HIV/AIDS. Among 257 HIV-infected adult patients seen between
      January 2006 and December 2010 in a tertiary hospital in Zaria, northern Nigeria,
      9 (3.5%) patients had clinical, serological, and brain imaging evidence of TE.
      All 9 patients had CD4 count of less than 50 cells/mm(3). Of the 9 patients, 7
      were antiretroviral therapy (ART)-naive, while 2 were cases of ART-induced TE
      immune reconstitution inflammatory syndrome. After administering intravenous
      dexamethasone for cerebral decompression and specific antitoxoplasma therapy,
      symptoms and signs resolved in 8 patients within 4 to 14 days, but 1 patient
      died. Our data suggest that even in the ART era in Nigeria, TE remains a fairly
      common cause of morbidity among HIV-infected patients due to late HIV diagnosis
      and significant immunosuppression at diagnosis. Early HIV diagnosis, early
      initiation of highly active ART, and routine prophylaxis against TE are
      imperative in combating the challenge of HIV/AIDS-related TE in Nigeria. 

PMID- 23962914
TI  - Label-free fluorimetric detection of histone using quaternized carbon dot-DNA
      nanobiohybrid.
AB  - A fluorimetric histone sensing technique is developed using quaternized carbon
      dot-DNA nanobiohybrid. The method is simple, specific, and can detect a minimum
      of 0.2 ng mL(-1) histone. 

PMID- 23962911
TI  - PharmGKB summary: very important pharmacogene information for cytochrome P450,
      family 2, subfamily C, polypeptide 8.

PMID- 23962916
TI  - Greenway siting and design: relationships with physical activity behaviors and
      user characteristics.
AB  - BACKGROUND: Greenways (GW) can be sited and designed in a variety of ways.
      However, the extent to which siting and design relate to GW user's demographic
      characteristics and physical activity (PA) is unknown. The purpose of this study
      was to compare 2 GWs that differed in terms of their siting and design, with
      respect to the aforementioned variables. METHODS: A trail intercept survey
      measuring PA, modes of GW access, and demographics was administered on 2 GWs
      (GWlinear vs. GWloop), which varied in siting and design characteristics.
      RESULTS: GWlinear (n = 216), compared with GWloop users (n = 400), accumulated
      significantly greater volumes of PA from both accessing and using the GW (P =
      .012). GW linear users were more likely to be younger, male, and never married;
      they were also more likely to engage in transportational PA (10.6 vs. 0.3%, P <=
      .001) and access the GW via active transit modes (37.0% vs. 4.2%, P <= .001).
      CONCLUSIONS: GW siting and design appears to be related to user characteristics,
      and the types and volumes of PA performed. These results should be considered by
      GW planners and designers to best serve the PA needs of the community.

PMID- 23962915
TI  - Culturing microglia from the neonatal and adult central nervous system.
AB  - Microglia are the resident macrophage-like cells of the central nervous system
      (CNS) and, as such, have critically important roles in physiological and
      pathological processes such as CNS maturation in development, multiple sclerosis,
      and spinal cord injury. Microglia can be activated and recruited to action by
      neuronal injury or stimulation, such as axonal damage seen in MS or ischemic
      brain trauma resulting from stroke. These immunocompetent members of the CNS are
      also thought to have roles in synaptic plasticity under non-pathological
      conditions. We employ protocols for culturing microglia from the neonatal and
      adult tissues that are aimed to maximize the viable cell numbers while minimizing
      confounding variables, such as the presence of other CNS cell types and cell
      culture debris. We utilize large and easily discernable CNS components (e.g.
      cortex, spinal cord segments), which makes the entire process feasible and
      reproducible. The use of adult cells is a suitable alternative to the use of
      neonatal brain microglia, as many pathologies studied mainly affect the postnatal
      spinal cord. These culture systems are also useful for directly testing the
      effect of compounds that may either inhibit or promote microglial activation.
      Since microglial activation can shape the outcomes of disease in the adult CNS,
      there is a need for in vitro systems in which neonatal and adult microglia can be
      cultured and studied.

PMID- 23962917
TI  - Predicting 2-year survival for radiation regimens in advanced non-small cell lung
      cancer.
AB  - AIMS: Total dose, dose per fraction, number of fractions and treatment time are
      important determinants of the biological effect of a radiation regimen. Several
      randomised clinical trials (RCTs) have tested a variety of dosing regimens in
      advanced unresected non-small cell lung cancer, but survival remains poor. This
      work used past RCT data to develop and validate a predictive model that could
      help in designing new radiation regimens for successful testing in RCTs.
      MATERIALS AND METHODS: Eleven RCTs that compared radiation regimens alone were
      used to define the relationship between radiation regimens and 2-year survival.
      On the basis of this relationship, predictive models were developed. Predicted
      values were internally and externally validated against observed values from the
      same 11 RCTs and 21 other RCTs. Scatter plots and Pearson's correlation
      coefficient (r) were used for validation. Finally, regimens were explored that
      could improve survival. RESULTS: Increments in the total dose, dose per day and
      the number of treatment days were associated with improved survival; increments
      in dose-squared and treatment weeks were associated with reduced survival. The
      observed and predicted values were similar on internal (r = 0.96) and external
      validation (r = 0.76). Regimens that delivered a higher total dose over a shorter
      time had higher survival rates compared with the standard (60 Gy, 30 fractions, 6
      weeks); survival may be improved by delivering the standard treatment in 5 weeks
      rather than 6 weeks. CONCLUSION: The developed model can predict the effect of
      thoracic radiation on survival in advanced non-small cell lung cancer patients.
      It is a useful tool for designing new radiation regimens for clinical trials.

PMID- 23962918
TI  - Deoxynivalenol and other selected Fusarium toxins in Swedish oats--occurrence and
      correlation to specific Fusarium species.
AB  - Fusarium moulds frequently contaminate oats and other cereals world-wide,
      including those grown in Northern Europe. To investigate the presence of
      toxigenic Fusarium species and their toxins in oats, samples were taken during
      2010 and 2011 in three geographical regions of Sweden (east, west, south). The
      samples were analysed by real-time PCR for the specific infection level of seven
      Fusarium species associated with oats and other cereals (Fusarium poae, Fusarium
      graminearum, Fusarium langsethiae, Fusarium culmorum, Fusarium tricinctum,
      Fusarium sporotrichioides and Fusarium avenaceum) and with a multi-mycotoxin
      method based on liquid chromatography/electrospray ionisation-tandem mass
      spectrometry (HPLC/ESI-MS/MS) for the detection of many fungal metabolites,
      including deoxynivalenol (DON), zearalenone (ZEA), nivalenol (NIV), T-2 toxin, HT
      2 toxins, moniliformin (MON), beauvericin (BEA) and enniatins (ENNs). Most
      samples contained at least four of the seven Fusarium species analysed and F.
      poae, F. langsethiae and F. avenaceum were present in approximately 90-100% of
      all samples. The most common toxins detected were DON, NIV, BEA and ENNs, which
      were present in more than 90% of samples. Most Fusarium species and their toxins
      occurred in higher concentrations in 2010 than in 2011, with the exception of DON
      and its main producer F. graminearum. Significant regional differences were
      detected for some moulds and mycotoxins, with higher levels of F. graminearum,
      DON and ZEA in western Sweden than in the east (P<0.05) and higher levels of F.
      tricinctum and MON in the south (P<0.05). Correlation analysis showed significant
      correlations between many Fusarium species and toxin levels. For example, F.
      tricinctum was significantly correlated to F. avenaceum (r = 0.72, P<0.001), DON
      to ZEA (r = 0.52, P<0.001), DON to F. graminearum (r = 0.77, P<0.001) and the sum
      of T-2 and HT-2 to F. langsethiae (r = 0.77, P<0.001). The multi-toxin approach
      employed allowed simultaneous detection of many Fusarium mycotoxins in each
      sample. In combination with real-time PCR analysis of seven toxigenic Fusarium
      spp., the results gave an overall picture of the presence of Fusarium and their
      toxins in Swedish oats and revealed significant annual and regional differences.
      This is the first study of the so-called emerging mycotoxins (e.g., ENNs, MON and
      BEA) in oats grown in Sweden.

PMID- 23962919
TI  - Deoxynivalenol and other selected Fusarium toxins in Swedish wheat--occurrence
      and correlation to specific Fusarium species.
AB  - Wheat is often infected by Fusarium species producing mycotoxins, which may pose
      health risks to humans and animals. Deoxynivalenol (DON) is the most important
      Fusarium toxin in Swedish wheat and has previously been shown to be produced
      mainly by Fusarium graminearum. However, less is known about the co-occurrence of
      DON and F. graminearum with other toxins and Fusarium species in Sweden. This
      study examined the distribution of the most important toxigenic Fusarium species
      and their toxins in winter wheat (2009 and 2011) and spring wheat (2010 and
      2011). DNA from seven species was quantified with qPCR and the toxin levels were
      quantified with a multitoxin analysis method based on liquid
      chromatography/electrospray ionisation-tandem mass spectrometry (HPLC/ESI-MS/MS).
      The method enabled detection of many fungal metabolites, including DON,
      zearalenone (ZEA), nivalenol (NIV), T-2 toxin, HT-2 toxins, moniliformin (MON),
      beauvericin (BEA), and enniatins (ENNs). It was found that Fusarium poae and
      Fusarium avenaceum were present in almost all samples. Other common Fusarium
      species were F. graminearum and F. culmorum, present in more than 70% of samples.
      Several species occurred at lower DNA levels in 2011 than in other years, but the
      reverse was true for F. graminearum and Fusarium langsethiae. The most prevalent
      toxins were ENNs, present in 100% of samples. DON was also common, especially in
      spring wheat, whereas ZEA and NIV were common in 2009 and in winter wheat, but
      less common in 2011 and in spring wheat. Only three samples of spring wheat
      contained T-2 or HT-2 above LOQ. Annual mean levels of several mycotoxins were
      significantly lower in 2011 than in other years, but the reverse applied for DON.
      The strongest correlations between mycotoxin and Fusarium DNA levels were found
      between F. avenaceum and ENNs (r(2) = 0.67) and MON (r(2) = 0.62), and F.
      graminearum and DON (r(2) = 0.74). These results show that several Fusarium
      species and toxins co-occur in wheat. The highest toxin levels were detected in
      spring wheat and DON and ENNs, the latter belonging to the group of so called
      "emerging toxins", which were the most prevalent toxins and those occurring at
      the highest levels.

PMID- 23962920
TI  - Pharmacology in the high tech age--new developments, opportunities and
      limitations.

PMID- 23962921
TI  - Interaction of ultrasonic waves with domain walls on nanocrystalline YIG.
AB  - The nanocrystalline YIG samples with different particle sizes (20-40 nm) has been
      prepared using microwave-hydrothermal method. As synthesized powders were
      characterized using XRD and TEM. The powders were pressed and sintered at three
      different temperatures i.e., 700  degrees C/30 min, 800  degrees C/30 min, 900 
      degrees C/30 min, using microwave furnace. The sintered samples were
      characterized using XRD and TEM. The sintered samples are monophasic in nature
      with average grain size ranging in between 72 nm and 90 nm. The thermal variation
      of ultrasonic velocities [longitudinal (V(l)) and transverse (V(S))] and
      longitudinal attenuation (alpha(l)) has been measured on sintered samples by the
      pulse transmissionmethod at 1 MHz, in the temperature range of 300-600 K. The
      room temperature velocity is found to be grain size dependent and decreases with
      increasing temperature, except near the Curie temperature, T(C), where a small
      anomaly is observed. The longitudinal attenuation (alpha(1)) at room temperature
      is also found to be more sample dependent. The temperature variation of
      ultrasonic longitudinal attenuation exhibits a sharp maximum just below Curie
      temperature (T(C)). The above observations were carried on in the demagnetized
      state, on the application of a saturation field of 380 mT, the anomaly observed
      in the thermal variation of velocities (longitudinal and transverse) and
      attenuation is found to disappears. The observed interaction of ultrasonic
      velocity with domain walls has been qualitatively explained with the help
      oftemperature variation of magneto-crystalline anisotropy constant (k(1)) and
      Landau's theory.

PMID- 23962922
TI  - A variant on the kappa opioid receptor gene (OPRK1) is associated with stress
      response and related drug craving, limbic brain activation and cocaine relapse
      risk.
AB  - Stress increases drug craving and relapse risk. The kappa opioid receptor gene
      (OPRK1) mediates stress responses. Here, we examined whether the OPRK1 rs6989250
      C>G affects stress-induced cocaine craving and cortisol responses, subsequent
      cocaine relapse risk and the neural response to stress using functional magnetic
      resonance imaging (fMRI) in cocaine dependence. Sixty-seven treatment-engaged,
      abstinent cocaine-dependent African-Americans were genotyped (CG: N=10; CC: N=57)
      and participated in a 3-day experiment in which they were exposed to personalized
      script-driven imagery of stress, drug cues and neutral scenarios, one condition
      per day, randomly assigned and counterbalanced across subjects. Repeated measures
      of craving and cortisol were obtained. The subjects were followed prospectively
      for 90 days to assess relapse risk. A follow-up preliminary fMRI experiment
      assessed neural responses to stress, drug cue and neutral conditions in matched
      CG (N=5) and CC (N=8) subgroups. We found greater stress-induced craving
      (P=0.019), higher cortisol during stress and cue relative to the neutral
      condition (P's<0.003), and increased cocaine relapse risk (P=0.0075) in the CG
      compared with the CC group. The CG relative to the CC group also showed greater
      activation of limbic and midbrain regions during stress and cues relative to the
      neutral condition with additional stress-induced activation in the right
      amygdala/hippocampus (P<0.05, whole-brain corrected). These results suggest that
      OPRK1 is associated with stress-induced craving and cortisol, hyperactive
      hypothalamus/thalamus-midbrain-cerebellum responses, and also associated with
      greater subsequent cocaine relapse risk. Future studies to replicate these
      findings in a larger sample size are warranted.

PMID- 23962923
TI  - CSF protein biomarkers predicting longitudinal reduction of CSF beta-amyloid42 in
      cognitively healthy elders.
AB  - beta-amyloid (Abeta) plaque accumulation is a hallmark of Alzheimer's disease
      (AD). It is believed to start many years prior to symptoms and is reflected by
      reduced cerebrospinal fluid (CSF) levels of the peptide Abeta1-42 (Abeta42). Here
      we tested the hypothesis that baseline levels of CSF proteins involved in
      microglia activity, synaptic function and Abeta metabolism predict the
      development of Abeta plaques, assessed by longitudinal CSF Abeta42 decrease in
      cognitively healthy people. Forty-six healthy people with three to four serial
      CSF samples were included (mean follow-up 3 years, range 2-4 years). There was an
      overall reduction in Abeta42 from a mean concentration of 211-195 pg ml(-1) after
      4 years. Linear mixed-effects models using longitudinal Abeta42 as the response
      variable, and baseline proteins as explanatory variables (n=69 proteins
      potentially relevant for Abeta metabolism, microglia or synaptic/neuronal
      function), identified 10 proteins with significant effects on longitudinal
      Abeta42. The most significant proteins were angiotensin-converting enzyme (ACE,
      P=0.009), Chromogranin A (CgA, P=0.009) and Axl receptor tyrosine kinase (AXL,
      P=0.009). Receiver-operating characteristic analysis identified 11 proteins with
      significant effects on longitudinal Abeta42 (largely overlapping with the
      proteins identified by linear mixed-effects models). Several proteins (including
      ACE, CgA and AXL) were associated with Abeta42 reduction only in subjects with
      normal baseline Abeta42, and not in subjects with reduced baseline Abeta42. We
      conclude that baseline CSF proteins related to Abeta metabolism, microglia
      activity or synapses predict longitudinal Abeta42 reduction in cognitively
      healthy elders. The finding that some proteins only predict Abeta42 reduction in
      subjects with normal baseline Abeta42 suggest that they predict future
      development of the brain Abeta pathology at the earliest stages of AD, prior to
      widespread development of Abeta plaques.

PMID- 23962927
TI  - Tucker apparatus for counterirritation.

PMID- 23962924
TI  - Differentiation from human pluripotent stem cells of cortical neurons of the
      superficial layers amenable to psychiatric disease modeling and high-throughput
      drug screening.
AB  - Cortical neurons of the superficial layers (II-IV) represent a pivotal neuronal
      population involved in the higher cognitive functions of the human and are
      particularly affected by psychiatric diseases with developmental manifestations
      such as schizophrenia and autism. Differentiation protocols of human pluripotent
      stem cells (PSC) into cortical neurons have been achieved, opening the way to in
      vitro modeling of neuropsychiatric diseases. However, these protocols commonly
      result in the asynchronous production of neurons typical for the different layers
      of the cortex within an extended period of culture, thus precluding the analysis
      of specific subtypes of neurons in a standardized manner. Addressing this issue,
      we have successfully captured a stable population of self-renewing late cortical
      progenitors (LCPs) that synchronously and massively differentiate into
      glutamatergic cortical neurons of the upper layers. The short time course of
      differentiation into neurons of these progenitors has made them amenable to high
      throughput assays. This has allowed us to analyze the capability of LCPs at
      differentiating into post mitotic neurons as well as extending and branching
      neurites in response to a collection of selected bioactive molecules. LCPs and
      cortical neurons of the upper layers were successfully produced from patient
      derived-induced PSC, indicating that this system enables functional studies of
      individual-specific cortical neurons ex vivo for disease modeling and therapeutic
      purposes. 

PMID- 23962928
TI  - Messing around Allentown: Paul Meyer Wood.

PMID- 23962925
TI  - Genome analysis reveals insights into physiology and longevity of the Brandt's
      bat Myotis brandtii.
AB  - Bats account for one-fifth of mammalian species, are the only mammals with
      powered flight, and are among the few animals that echolocate. The insect-eating
      Brandt's bat (Myotis brandtii) is the longest-lived bat species known to date
      (lifespan exceeds 40 years) and, at 4-8 g adult body weight, is the most extreme
      mammal with regard to disparity between body mass and longevity. Here we report
      sequencing and analysis of the Brandt's bat genome and transcriptome, which
      suggest adaptations consistent with echolocation and hibernation, as well as
      altered metabolism, reproduction and visual function. Unique sequence changes in
      growth hormone and insulin-like growth factor 1 receptors are also observed. The
      data suggest that an altered growth hormone/insulin-like growth factor 1 axis,
      which may be common to other long-lived bat species, together with adaptations
      such as hibernation and low reproductive rate, contribute to the exceptional
      lifespan of the Brandt's bat. 

PMID- 23962929
TI  - Should we offer the surgeon a break?

PMID- 23962930
TI  - Cardiac output monitoring is already standard.

PMID- 23962931
TI  - In reply.

PMID- 23962932
TI  - In reply.

PMID- 23962933
TI  - Laterality of motor control and consciousness shares the same hemisphere.

PMID- 23962934
TI  - In reply.

PMID- 23962935
TI  - Postanesthesia evaluation of neuromuscular function.

PMID- 23962936
TI  - In reply.

PMID- 23962937
TI  - A plea for the cautious use of droperidol.

PMID- 23962938
TI  - In reply.

PMID- 23962939
TI  - An updated report by the American Society of Anesthesiologists Task Force on
      management of the difficult airway: where is the aspiration risk assessment?

PMID- 23962940
TI  - Updated difficult airway algorithm: confusing and contradictory.

PMID- 23962941
TI  - In reply.

PMID- 23962942
TI  - Hydroxyethyl starch 130/0.4 and postoperative acute kidney injury.

PMID- 23962943
TI  - Hydroxyethyl starch 130/0.4: safe for the kidney in surgical patients?

PMID- 23962944
TI  - In reply.

PMID- 23962945
TI  - Epidural and continuous wound infusion in enhanced recovery protocols.

PMID- 23962946
TI  - In reply.

PMID- 23962947
TI  - Transparent guideline methodology needed.

PMID- 23962948
TI  - In reply.

PMID- 23962953
TI  - Face or body? Oxytocin improves perception of emotions from facial expressions in
      incongruent emotional body context.
AB  - The neuropeptide oxytocin (OT) has been repeatedly reported to play an essential
      role in the regulation of social cognition in humans in general, and specifically
      in enhancing the recognition of emotions from facial expressions. The later was
      assessed in different paradigms that rely primarily on isolated and
      decontextualized emotional faces. However, recent evidence has indicated that the
      perception of basic facial expressions is not context invariant and can be
      categorically altered by context, especially body context, at early perceptual
      levels. Body context has a strong effect on our perception of emotional
      expressions, especially when the actual target face and the contextually expected
      face are perceptually similar. To examine whether and how OT affects emotion
      recognition, we investigated the role of OT in categorizing facial expressions in
      incongruent body contexts. Our results show that in the combined process of
      deciphering emotions from facial expressions and from context, OT gives an
      advantage to the face. This advantage is most evident when the target face and
      the contextually expected face are perceptually similar. 

PMID- 23962954
TI  - Superconductivity of BaLi4 under pressure.
AB  - We studied the pressure-induced superconductivity of BaLi4 up to 53 GPa by means
      of electrical resistivity in a diamond anvil cell. Superconductivity in BaLi4 is
      first observed at a pressure of 5.4 GPa with a superconducting critical
      temperature (Tc) of 4.5 K. Below 2 GPa, superconductivity is not observed above
      the minimum temperature achievable in the current study, 2 K. Between 5.4 and 12
      GPa, the Tc increases steeply to its maximum value of 7 K. Above 12 GPa, the
      pressure dependence of Tc is complex and the sign of dTc/dP changes several times
      in going up to the maximum pressure studied, of 53 GPa. 

PMID- 23962955
TI  - Association of decreased prefrontal hemodynamic response during a verbal fluency
      task with EGR3 gene polymorphism in patients with schizophrenia and in healthy
      individuals.
AB  - The early growth response 3 (EGR3) gene is an immediate early gene that is
      expressed throughout the brain and has been suggested as a potential
      susceptibility gene for schizophrenia (SZ). EGR3 impairment is associated with
      various neurodevelopmental dysfunctions, and some animal studies have reported a
      role for EGR3 function in the prefrontal cortex. Therefore, EGR3 genotype
      variation may be reflected in prefrontal function. By using multi-channel near
      infrared spectroscopy (NIRS) in an imaging genetics approach, we tested for an
      association between the EGR3 gene polymorphism and prefrontal hemodynamic
      response during a cognitive task in patients with SZ. We assessed 73 chronic
      patients with SZ and 73 age-, gender-, and genotype-matched healthy controls (HC)
      who provided written informed consent. We used NIRS to measure changes in
      prefrontal oxygenated hemoglobin concentration (oxyHb) during the letter version
      of a verbal fluency task (VFT). Statistical comparisons were performed among EGR3
      genotype subgroups (rs35201266, GG/GA/AA). The AA genotype group showed
      significantly smaller oxyHb increases in the left dorsolateral prefrontal cortex
      (DLPFC) during the VFT than the GG and GA genotype groups; this was true for both
      patients with SZ and HC. Our findings provide in vivo human evidence of a
      significant influence of EGR3 polymorphisms on prefrontal hemodynamic activation
      level in healthy adults and in patients with SZ. Genetic variation in EGR3 may
      affect prefrontal function through neurodevelopment. This study illustrates the
      usefulness of NIRS in imaging genetics investigations on psychiatric disorders. 

PMID- 23962957
TI  - Richness of information about novel words influences how episodic and semantic
      memory networks interact during lexicalization.
AB  - The complementary learning systems account of declarative memory suggests two
      distinct memory networks, a fast-mapping, episodic system involving the
      hippocampus, and a slower semantic memory system distributed across the neocortex
      in which new information is gradually integrated with existing representations.
      In this study, we investigated the extent to which these two networks are
      involved in the integration of novel words into the lexicon after extensive
      learning, and how the involvement of these networks changes after 24h. In
      particular, we explored whether having richer information at encoding influences
      the lexicalization trajectory. We trained participants with two sets of novel
      words, one where exposure was only to the words' phonological forms (the form
      only condition), and one where pictures of unfamiliar objects were associated
      with the words' phonological forms (the picture-associated condition). A
      behavioral measure of lexical competition (indexing lexicalization) indicated
      stronger competition effects for the form-only words. Imaging (fMRI) results
      revealed greater involvement of phonological lexical processing areas immediately
      after training in the form-only condition, suggesting that tight connections were
      formed between novel words and existing lexical entries already at encoding.
      Retrieval of picture-associated novel words involved the episodic/hippocampal
      memory system more extensively. Although lexicalization was weaker in the picture
      associated condition, overall memory strength was greater when tested after a
      24hour delay, probably due to the availability of both episodic and lexical
      memory networks to aid retrieval. It appears that, during lexicalization of a
      novel word, the relative involvement of different memory networks differs
      according to the richness of the information about that word available at
      encoding. 

PMID- 23962956
TI  - Simultaneous EEG-fMRI reveals a temporal cascade of task-related and default-mode
      activations during a simple target detection task.
AB  - Focused attention continuously and inevitably fluctuates, and to completely
      understand the mechanisms responsible for these modulations it is necessary to
      localize the brain regions involved. During a simple visual oddball task, neural
      responses measured by electroencephalography (EEG) modulate primarily with
      attention, but source localization of the correlates is a challenge. In this
      study we use single-trial analysis of simultaneously-acquired scalp EEG and
      functional magnetic resonance image (fMRI) data to investigate the blood oxygen
      level dependent (BOLD) correlates of modulations in task-related attention, and
      we unravel the temporal cascade of these transient activations. We hypothesize
      that activity in brain regions associated with various task-related cognitive
      processes modulates with attention, and that their involvements occur transiently
      in a specific order. We analyze the fMRI BOLD signal by first regressing out the
      variance linked to observed stimulus and behavioral events. We then correlate the
      residual variance with the trial-to-trial variation of EEG discriminating
      components for identical stimuli, estimated at a sequence of times during a
      trial. Post-stimulus and early in the trial, we find activations in right
      lateralized frontal regions and lateral occipital cortex, areas that are often
      linked to task-dependent processes, such as attentional orienting, and decision
      certainty. After the behavioral response we see correlates in areas often
      associated with the default-mode network and introspective processing, including
      precuneus, angular gyri, and posterior cingulate cortex. Our results demonstrate
      that during simple tasks both task-dependent and default-mode networks are
      transiently engaged, with a distinct temporal ordering and millisecond timescale.

PMID- 23962958
TI  - Meta-analysis of the effects of indoor nitrogen dioxide and gas cooking on asthma
      and wheeze in children.
AB  - BACKGROUND: Since the meta-analysis on the association between indoor nitrogen
      dioxide (NO2) and childhood respiratory illness in 1992, many new studies have
      been published. The quantitative effects of indoor NO2 on respiratory illness
      have not been estimated in a formal meta-analysis since then. We aimed to
      quantify the association of indoor NO2 and its main source (gas cooking) with
      childhood asthma and wheeze. METHODS: We extracted the association between indoor
      NO2 (and gas cooking) and childhood asthma and wheeze from population studies
      published up to 31 March 2013. Data were analysed by inverse-variance-weighted,
      random-effects meta-analysis. Sensitivity analyses were conducted for different
      strata. Publication bias and heterogeneity between studies were investigated.
      RESULTS: A total of 41 studies met the inclusion criteria. The summary odds ratio
      from random effects meta-analysis for asthma and gas cooking exposure was 1.32
      [95% confidential interval (CI) 1.18-1.48], and for a 15-ppb increase in NO2 it
      was 1.09 (95% CI 0.91-1.31). Indoor NO2 was associated with current wheeze
      (random effects OR 1.15; 95% CI 1.06-1.25). The estimates did not vary much with
      age or between regions. There was no evidence of publication bias. CONCLUSIONS:
      This meta-analysis provides quantitative evidence that, in children, gas cooking
      increases the risk of asthma and indoor NO2 increases the risk of current wheeze.

PMID- 23962959
TI  - An in-vitro preparation of isolated enteric neurons and glia from the myenteric
      plexus of the adult mouse.
AB  - The enteric nervous system is a vast network of neurons and glia running the
      length of the gastrointestinal tract that functionally controls gastrointestinal
      motility. A procedure for the isolation and culture of a mixed population of
      neurons and glia from the myenteric plexus is described. The primary cultures can
      be maintained for over 7 days, with connections developing among the neurons and
      glia. The longitudinal muscle strip with the attached myenteric plexus is
      stripped from the underlying circular muscle of the mouse ileum or colon and
      subjected to enzymatic digestion. In sterile conditions, the isolated neuronal
      and glia population are preserved within the pellet following centrifugation and
      plated on coverslips. Within 24-48 hr, neurite outgrowth occurs and neurons can
      be identified by pan-neuronal markers. After two days in culture, isolated
      neurons fire action potentials as observed by patch clamp studies. Furthermore,
      enteric glia can also be identified by GFAP staining. A network of neurons and
      glia in close apposition forms within 5-7 days. Enteric neurons can be
      individually and directly studied using methods such as immunohistochemistry,
      electrophysiology, calcium imaging, and single-cell PCR. Furthermore, this
      procedure can be performed in genetically modified animals. This methodology is
      simple to perform and inexpensive. Overall, this protocol exposes the components
      of the enteric nervous system in an easily manipulated manner so that we may
      better discover the functionality of the ENS in normal and disease states.

PMID- 23962960
TI  - Using photovoice to explore the unique life perspectives of youth with sickle
      cell disease: a pilot study.
AB  - OBJECTIVES: Sickle cell disease (SCD) has been associated with multiple physical
      and psychosocial challenges but less is known about the experience of living with
      the disease, particularly from the perspective of children/adolescents.
      Photovoice uses photography to access the experiences of individuals living with
      a disease and provides them with a voice for expression. It provides a unique
      approach to exploring the perspective of children/adolescents with SCD. This
      pilot study examines the perspective of children/adolescents with SCD using
      photovoice, both to gain understanding of the perspective of these patients and
      the utility of the research method with this population. METHOD: Twelve
      participants with SCD between the ages of 6 and 14 years participated in this
      study. Participants took photographs during camp and completed qualitative
      interviews afterward to explore their perspective on life with SCD and experience
      with the photovoice method. RESULTS: Main themes derived from content analysis of
      the qualitative interviews included the following: (a) importance of friends, (b)
      controlling symptoms, and (c) importance of camp. CONCLUSION: This study
      demonstrated that (a) a camp can provide a beneficial social outlet with peers
      with SCD, (b) children/adolescents with SCD are able to manage their complex
      symptoms at a young age, and (c) photovoice is a useful methodology for
      children/adolescents with SCD and potentially other chronic illnesses.

PMID- 23962961
TI  - Markov chain Monte Carlo sampling of gene genealogies conditional on unphased SNP
      genotype data.
AB  - The gene genealogy is a tree describing the ancestral relationships among genes
      sampled from unrelated individuals. Knowledge of the tree is useful for inference
      of population-genetic parameters and has potential application in gene-mapping.
      Markov chain Monte Carlo approaches that sample genealogies conditional on
      observed genetic data typically assume that haplotype data are observed even
      though commonly-used genotyping technologies provide only unphased genotype data.
      We have extended our haplotype-based genealogy sampler, sampletrees, to handle
      unphased genotype data. We use the sampled haplotype configurations as a
      diagnostic for adequate sampling of the tree space based on the reasoning that if
      haplotype sampling is restricted, sampling from the tree space will also be
      restricted. We compare the distributions of sampled haplotypes across multiple
      runs of sampletrees, and to those estimated by the phase inference program,
      PHASE. Performance was excellent for the majority of individuals as shown by the
      consistency of results across multiple runs. However, for some individuals in
      some datasets, sampletrees had problems sampling haplotype configurations; longer
      run lengths would be required for these datasets. For many datasets though, we
      expect that sampletrees will be useful for sampling from the posterior
      distribution of gene genealogies given unphased genotype data.

PMID- 23962962
TI  - CuBr for KA(2) reaction: en route to propargylic amines bearing a quaternary
      carbon center.
AB  - A highly efficient CuBr-catalyzed coupling of ketones, amines and alkynes (KA(2))
      forming propargylic amines bearing a quaternary carbon center with the broadest
      scope so far has been developed. 

PMID- 23962963
TI  - Asenapine in the treatment of borderline personality disorder: an atypical
      antipsychotic alternative.
AB  - Many individuals with borderline personality disorder (BPD) receive medical
      treatment in clinical practice, although to date, there are no drugs specifically
      available for BPD. The recent Cochrane guideline suggests a benefit from using
      second-generation antipsychotics such as olanzapine or aripiprazole;
      nevertheless, side effects limit their use. Asenapine is a novel FDA-approved
      atypical antipsychotic for schizophrenia and bipolar disorder. However, it has
      not yet been tested for BPD. The goal of this observational open-label study was
      to assess the safety, tolerability and efficacy of asenapine in a series of cases
      of patients with BPD. Twelve individuals with BPD were recruited and treated with
      asenapine during an 8-week period. Eight individuals completed the study; a
      significant improvement was observed in the CGI-BPD (P<0.001) and BSL-23
      (P<0.048) scales for BPD symptomatology. Besides, there was a significant
      improvement in the general psychopathology domains (BPRS, P<0.004), whereas no
      significant differences were observed in depressive symptoms. No serious adverse
      effects were reported and a significant weight reduction was observed (P=0.002).
      Asenapine appears to be a safe and effective agent in the treatment of patients
      with BPD, especially when other alternatives are not tolerated. These preliminary
      findings should be replicated in a controlled clinical trial. 

PMID- 23962964
TI  - [Loiasis, a cause of eosinophilia to consider].

PMID- 23962965
TI  - Endothelin ETB1 receptor agonism as a new therapeutic strategy in pulmonary
      arterial hypertension and chronic heart failure.
AB  - Pulmonary arterial hypertension and post-ischemic chronic heart failure are
      highly prevalent diseases with high morbidity and mortality rates due to chronic
      vascular injury and extensive remodeling responses at the level of the vessel
      walls. Endothelins play a central role in this setting, through a complex
      signaling system that mainly affects endothelial and vascular smooth muscle
      cells. ETA and ETB2 endothelin receptors are thought to mediate pro-ischemic
      responses, while ETB1 receptor activity could account for the overall protective
      effect of ETB signaling in physiology. The pharmacologic modulation of the
      endothelin system has mainly focused on the dual non-selective blockade of ETA
      and ETB endothelin receptors or to the selective blockade of ETA-related pathways
      to date. Good clinical results were achieved in the setting of pulmonary
      hypertension but no advantage has been demonstrated for heart failure. Restoring
      and enhancing the physiological protective role of ETB1-signaling with
      concomitant blockade of ETB2 could possibly improve the efficacy of current
      therapies in the setting of pulmonary arterial hypertension and post-ischemic
      chronic heart failure. 

PMID- 23962966
TI  - Horace Wells' "Humbug Affair" occurred at Massachusetts General Hospital? Humbug!

PMID- 23962967
TI  - Horace wells' demonstration of nitrous oxide in Boston.
AB  - Horace Wells, a dentist in Hartford, Connecticut, first used nitrous oxide in
      dentistry in December 1844. A few weeks later he travelled to Boston,
      Massachusetts, to demonstrate to physicians and dentists the use of nitrous oxide
      in painful procedures. Wells' unsuccessful demonstration of nitrous oxide for the
      extraction of a tooth is well known, but other details of this trip are poorly
      understood. A description of Wells' visit to Boston was compiled using
      information from 21 statements and 5 newspaper notices. The precise date and
      location of Wells' demonstration could not be determined. There is no primary
      evidence that Wells' demonstration occurred in the surgical amphitheater (Ether
      Dome) at Massachusetts General Hospital. Wells' demonstration of nitrous oxide
      probably occurred around the end of January 1845, in a public hall on Washington
      Street, Boston. 

PMID- 23962968
TI  - Consciousness and the 21st century operating room.

PMID- 23962969
TI  - Palladium nanoparticles supported on a triptycene-based microporous polymer:
      highly active catalysts for CO oxidation.
AB  - Pd nanoparticles were well dispersed on a new triptycene-based microporous
      polymer support by the gas bubbling-assisted membrane reduction (GBMR) method.
      The stability of Pd nanoparticles is improved by the porous support, and the
      materials show excellent performance for CO oxidation. 

PMID- 23962970
TI  - pH dynamics in sewers and its modeling.
AB  - pH variation in sewers has a significant effect on hydrogen sulfide production
      and emissions, and hence its accurate prediction is critical for the optimization
      of mitigation strategies. In this study, the nature and dynamics of pH variation
      in a sewer system is examined. Three sewer systems collecting domestic wastewater
      were monitored, with pH in all cases showing large diurnal variations. pH in
      fresh sewage in all three cases had a very similar trend with maximum pH in the
      range of 8.5-8.7. pH variation in fresh sewage followed the same pattern as the
      sewage flow rate, suggesting that sewage pH is influenced by household water use.
      Nitrogen content of the wastewater was found to be the most influential factor
      causing pH variation in fresh sewage, with the total ammonium concentration
      variation well correlated with the pH variation. A methodology for predicting pH
      variation in sewers is developed and calibration protocols proposed. The
      methodology, which is based on the concept of charge balance, was validated using
      titration curves and field pH data. Measurement of the total ammonium
      concentration in fresh sewage was found necessary and adequate for the
      calibration of the charge balance-based pH model. 

PMID- 23962971
TI  - Epistatic interaction between CRHR1 and AVPR1b variants as a predictor of major
      depressive disorder.
AB  - OBJECTIVE: Genes involved in the regulation of the hypothalamus-pituitary-adrenal
      axis are responsible for altered susceptibility to mood disorders. The aim of
      this study was to analyze the possible association of CRHR1 and AVPR1b gene
      variants with bipolar disorder and major depressive disorder (MDD). METHODS: In
      the study, we included 486 patients with bipolar disorder and 215 patients with
      MDD. Consensus diagnosis was made according to Diagnostic and Statistical Manual
      of Mental Disorders, 4th ed. (DSM-IV) criteria, using the Structured Clinical
      Interview for DSM Disorders. The control group consisted of 712 healthy
      participants. Genotyping of CRHR1 and AVPR1b polymorphisms was performed using
      TaqMan single nucleotide polymorphism genotyping assays. Linkage disequilibrium
      analysis was carried out on Haploview. Gene-gene interactions were analyzed using
      the multifactor dimensionality reduction method. RESULTS: By single marker
      analysis we have found an association of rs28536160 of AVPR1b and rs4076452 and
      rs16940655 of CRHR1 with mood disorders (P=0.036, 0.0013, and 0.003,
      respectively). We observed strong linkage disequilibrium between seven CRHR1
      polymorphisms grouped in two haplotype blocks; however, none of them showed an
      association with MDD or bipolar disorder. Similarly, no association was found for
      three of four strongly linked AVPR1b polymorphisms. Gene-gene interaction
      analysis revealed a significant epistatic interaction between AVPR1b and CRHR1
      genes in susceptibility to MDD (P=0.017). CONCLUSION: Polymorphisms of CRHR1 and
      AVPR1b may modify susceptibility to mood disorders.

PMID- 23962972
TI  - Association between dopamine D4 receptor genotype and trait impulsiveness.

PMID- 23962973
TI  - Marine protected area improves yield without disadvantaging fishers.
AB  - Potential fishery benefits of Marine Protected Areas (MPAs) are widely
      acknowledged, yet seldom demonstrated, as fishery data series that straddle MPA
      establishment are seldom available. Here we postulate, based on a 15-year time
      series of nation-wide, spatially referenced catch and effort data, that the
      establishment of the Goukamma MPA (18 km alongshore; 40 km2) benefited the
      adjacent fishery for roman (Chrysoblephus laticeps), a South African endemic
      seabream. Roman-directed catch-per-unit-effort (CPUE) in the vicinity of the new
      MPA immediately increased, contradicting trends across this species'
      distribution. The increase continued after 5 years, the time lag expected for
      larval export, effectively doubling the pre-MPA CPUE after 10 years. We find no
      indication that establishing the MPA caused a systematic drop in total catch or
      increased travel distances for the fleet. Our results provide rare empirical
      evidence of rapidly increasing catch rates after MPA implementation without
      measurable disadvantages for fishers.

PMID- 23962974
TI  - A mononuclear cobalt(II)-dithienylethene complex showing slow magnetic relaxation
      and photochromic behavior.
AB  - Mononuclear complex Co(hpbdti)2.3CH3OH (1) was synthesized [hpbdtiH = 2-(2
      hydroxyphenyl)-4,5-bis(2,5-dimethyl(3-thienyl))-1H-imidazole], showing multiple
      step field-induced slow magnetic relaxation behaviors, and photochromic
      properties in CH2Cl2-CH3CN solution.

PMID- 23962976
TI  - The effects of a school-based psychosocial intervention on resilience and health
      outcomes among vulnerable children.
AB  - Responding to the psychosocial health needs of the vulnerable population has been
      considered as a significant public health issue that must be addressed through
      access to public health professionals. The study adopted a quasi-experimental
      design to evaluate the impact of a training program on nurses and teachers'
      knowledge of psychosocial health needs of vulnerable children and the impact this
      had on children's resilience and psychosocial health outcomes (self-esteem,
      social connection, anxiety, and depression). The result showed a significant
      increase in the knowledge mean scores of both nurses and teachers 6 weeks post
      intervention. Children's depression scores significantly reduced post
      intervention. Their resilience, self-esteem, and social connection were also
      significantly improved, while no significant reduction was found in their anxiety
      scores. The results of the pilot study suggest that a more rigorous study be
      conducted to further ascertain the effectiveness of the various interventions
      used in this study while taking into consideration the challenges raised by the
      authors. 

PMID- 23962975
TI  - The onset of ferromagnetism and superconductivity in [La0.7Sr0.3MnO3(n
      u.c.)/YBa2Cu3O7(2 u.c.)]20 superlattices.
AB  - With the aim of studying the interface magnetism, the onset of ferromagnetism and
      the onset of the transition to the superconducting state a series of
      [La0.7Sr0.3MnO3(n u.c.)/YBa2Cu3O7(2 u.c.)]20 (LSMO/YBCO) superlattices with
      nominally varying layer thickness of the LSMO from one to four unit cells (u.c.)
      was prepared and characterized by x-ray diffraction, electronic transport,
      magnetization and ferromagnetic resonance measurements. Spontaneous magnetization
      was observed for a superlattice with four u.c. LSMO layer thickness in a
      multilayer structure. Superlattices with 3 u.c. of LSMO and lower layer
      thicknesses did not show a signature of ferromagnetism. The onset of
      superconductivity was observed for superlattices with one and two LSMO layer u.c.
      thickness. 

PMID- 23962977
TI  - Gavaging adult zebrafish.
AB  - The zebrafish has become an important in vivo model in biomedical research.
      Effective methods must be developed and utilized to deliver compounds or agents
      in solutions for scientific research. Current methods for administering compounds
      orally to adult zebrafish are inaccurate due to variability in voluntary
      consumption by the fish. A gavage procedure was developed to deliver precise
      quantities of infectious agents to zebrafish for study in biomedical research.
      Adult zebrafish over 6 months of age were anesthetized with 150 mg/L of buffered
      MS-222 and gavaged with 5 MUl of solution using flexible catheter implantation
      tubing attached to a cut 22-G needle tip. The flexible tubing was lowered into
      the oral cavity of the zebrafish until the tip of the tubing extended past the
      gills (approximately 1 cm). The solution was then injected slowly into the
      intestinal tract. This method was effective 88% of the time, with fish recovering
      uneventfully. This procedure is also efficient as one person can gavage 20-30
      fish in one hour. This method can be used to precisely administer agents for
      infectious diseases studies, or studies of other compounds in adult zebrafish.

PMID- 23962979
TI  - The tyrosine kinase Syk differentially regulates Toll-like receptor signaling
      downstream of the adaptor molecules TRAF6 and TRAF3.
AB  - Toll-like receptors (TLRs) are a major family of pattern recognition receptors,
      and they play a crucial role in innate immune responses. Activation of TLR4
      signaling at the plasma membrane by its ligand lipopolysaccharide (LPS)
      stimulates a proinflammatory pathway dependent on the E3 ubiquitin ligase TRAF6
      (tumor necrosis factor receptor-associated factor 6) and the kinase TAK1
      (transforming growth factor beta-activated kinase 1), whereas TLR4 signaling at
      endosomes stimulates the production of type I interferons (IFNs) through a
      pathway that depends on TRAF3 and the kinase TBK1 (TANK-binding kinase-1). We
      found that the nonreceptor tyrosine kinase Syk partially mediated the endocytosis
      of TLR4, but it also played a dual role in TLR4-mediated signaling. LPS-dependent
      stimulation of TLR4 in Syk-deficient macrophages led to enhanced activation of
      TAK1 and increased production of proinflammatory cytokines compared to that in
      wild-type macrophages. In contrast, Syk-deficient macrophages exhibited decreased
      TLR4-dependent activation of TBK1 signaling and production of type I IFNs. We
      found that Syk was present in both TRAF6- and TRAF3-containing signaling
      complexes; however, the LPS-dependent, lysine 63-linked ubiquitination of TRAF6
      and TRAF3 was oppositely regulated by Syk. We identified the domains of Syk that
      interacted with TRAF3, TRAF6, TAK1, and TBK1, factors activated by multiple TLRs,
      which suggests that Syk may act as a common regulator of various TLR responses.
      Together, our results demonstrate the opposing regulatory roles of Syk in TLR
      mediated TRAF6 and TRAF3 signaling pathways, which suggests that Syk may fine
      tune the innate immune response to lessen inflammation. 

PMID- 23962978
TI  - Conserved regulators of nucleolar size revealed by global phenotypic analyses.
AB  - Regulation of cell growth is a fundamental process in development and disease
      that integrates a vast array of extra- and intracellular information. A central
      player in this process is RNA polymerase I (Pol I), which transcribes ribosomal
      RNA (rRNA) genes in the nucleolus. Rapidly growing cancer cells are characterized
      by increased Pol I-mediated transcription and, consequently, nucleolar
      hypertrophy. To map the genetic network underlying the regulation of nucleolar
      size and of Pol I-mediated transcription, we performed comparative, genome-wide
      loss-of-function analyses of nucleolar size in Saccharomyces cerevisiae and
      Drosophila melanogaster coupled with mass spectrometry-based analyses of the
      ribosomal DNA (rDNA) promoter. With this approach, we identified a set of
      conserved and nonconserved molecular complexes that control nucleolar size.
      Furthermore, we characterized a direct role of the histone information regulator
      (HIR) complex in repressing rRNA transcription in yeast. Our study provides a
      full-genome, cross-species analysis of a nuclear subcompartment and shows that
      this approach can identify conserved molecular modules.

PMID- 23962981
TI  - Potential pathological and functional links between long noncoding RNAs and
      hematopoiesis.
AB  - Differential abundance and activity of long noncoding RNAs (lncRNAs) are
      recognized as the hallmark features in various diseases. We highlight the lncRNAs
      that play a functional role in the development of blood cells. Many lncRNAs and
      the protein complexes within which they interact have been implicated in various
      types of cancers. Multiple lncRNAs participate in normal and may be implicated in
      malignant hematopoiesis associated with blood cell cancers, such as leukemia, by
      regulating gene expression through such mechanisms as redirecting chromatin
      remodeling complexes and activating epigenetic silencing, either of which can
      inactivate tumor suppressor genes or activate oncogenes. Because of their
      potential importance in cancers of the blood, lncRNAs may be useful as diagnostic
      and prognostic markers, and it may be possible to develop lncRNA-mediated
      therapy. 

PMID- 23962980
TI  - A physical interaction between the adaptor proteins DOK3 and DAP12 is required to
      inhibit lipopolysaccharide signaling in macrophages.
AB  - DNAX-activating protein of 12 kD (DAP12) is an immunoreceptor tyrosine-based
      activation motif (ITAM)-containing adaptor protein found in myeloid cells and
      natural killer cells, and it couples to various receptors that mediate either
      cellular activation or inhibition. DAP12 inhibits Toll-like receptor (TLR)
      signaling, such as that of TLR4 in response to its ligand lipopolysaccharide
      (LPS), as well as cytokine responses by coupling to TREM2 (triggering receptor
      expressed on myeloid cells 2) at the plasma membrane. Understanding the
      mechanisms that inhibit inflammatory responses in macrophages is important for
      the development of therapies to treat inflammatory diseases. We show that
      inhibition of LPS responses by DAP12 is mediated by the adaptor protein DOK3
      (downstream of kinase 3). DOK3 physically associated with the ITAM of DAP12
      through its phosphotyrosine-binding domain. In response to LPS, DOK3 was
      phosphorylated in a DAP12- and Src-dependent manner, which led to translocation
      of phosphorylated DOK3 to the plasma membrane. DOK3-deficient cells exhibited
      increased production of proinflammatory cytokines and activation of extracellular
      signal-regulated kinase (ERK). Compared to wild-type mice, DOK3-deficient mice
      had increased susceptibility to challenge with a sublethal dose of LPS and
      produced increased serum concentrations of the inflammatory cytokine tumor
      necrosis factor-alpha (TNF-alpha). Together, these data suggest the mechanism by
      which DAP12 and TREM2 inhibit LPS signaling in macrophages to prevent
      inflammation. 

PMID- 23962982
TI  - Exercise training and rehabilitation in pulmonary arterial hypertension:
      rationale and current data evaluation.
AB  - Pulmonary arterial hypertension (PAH) is characterized by reduced functional
      capacity and health-related quality of life. Despite the progress made in recent
      years in disease-targeted therapies with improvement in prognosis, PAH patients
      often experience progressive exercise intolerance. Exercise rehabilitation is
      beneficial and has become a standard of care in patients with systolic heart
      failure and chronic obstructive pulmonary disease. However, although PAH patients
      present with similar exertional limitation and often share common hemodynamic,
      ventilatory, and skeletal muscle derangements, exercise rehabilitation was
      discouraged in PAH patients because of concerns of clinical deterioration and
      adverse outcomes. In recent years, several small-scale studies have demonstrated
      that closely supervised and monitored exercise training programs may have
      potential benefits in the management of stable PAH patients, improving exercise
      capacity and quality of life, with an acceptable low risk of adverse events in
      the studied populations. This review describes the emerging clinical data
      supporting the efficacy and safety of exercise training in PAH patients. The
      review provides a perspective on the pathophysiological impairments contributing
      to exercise intolerance in these patients and critically project from the proven
      evidence-based benefits of cardiopulmonary rehabilitation in chronic heart
      failure and chronic obstructive pulmonary disease on the PAH population. 

PMID- 23962983
TI  - Reply to the comment on "On the dual emission of p-dimethylaminobenzonitrile and
      its photophysical implications" by J. Catalan, Phys. Chem. Chem. Phys., 2013, 15,
      8811-8820.

PMID- 23962984
TI  - Understanding the lid movements of LolA in Escherichia coli using molecular
      dynamics simulation and in silico point mutation.
AB  - The Lol system in Escherichia coli is involved in localization of lipoproteins
      and hence is essential for growth of the organism. LolA is a periplasmic
      chaperone that binds to outer-membrane specific lipoproteins and transports them
      from inner membrane to outer membrane through LolB. The hydrophobic lipid-binding
      cavity of LolA consists of alpha-helices which act as a lid in regulating the
      transfer of lipoproteins from LolA to LolB. The current study aims to investigate
      the structural changes observed in LolA during the transition from open to closed
      conformation in the absence of lipoprotein. Molecular dynamics (MD) simulations
      were carried out for two LolA crystal structures; LolA(R43L), and in silico
      mutated MsL43R for a simulation time of 50 ns in water environment. We have
      performed an in silico point mutation of leucine to arginine in MsL43R to
      evaluate the importance of arginine to induce structural changes and impact the
      stability of protein structure. A complete dynamic analysis of open to closed
      conformation reveals the existence of two distinct levels; closing of lid and
      closing of entrance of hydrophobic cavity. Our analysis reveals that the
      structural flexibility of LolA is an important factor for its role as a
      periplasmic chaperone.

PMID- 23962985
TI  - Accurate measurement of concurrent flexion-extension and internal-external
      rotations in smart knee prostheses.
AB  - In this paper, we present a magnetic measurement system for integration into
      smart knee prostheses to accurately measure the combination of two knee
      rotations; namely flexion-extension (FE) and internal-external (IE) rotations.
      This measurement system consists of two permanent magnets inserted into the
      femoral and tibial parts of the prosthesis and a configuration of anisotropic
      magneto-resistive sensors placed in its polyethylene part. The sensor
      configuration was designed according to the sensitivity analysis. Several angle
      estimators were defined to obtain accurate angle estimations. These estimators
      ranged from different linear regression models to artificial neural networks. The
      estimators were trained and tested on several dynamic measurements of rotations
      of the prosthesis parts in a mechanical knee simulator also monitored using a
      stereophotogrammetry motion capture system. Considering the best estimators, the
      errors (mean +/- SD) were 0.0 degrees  +/- 0.9 degrees  and 0.2 degrees  +/- 1.1
      degrees  for IE and FE angle estimations, respectively. The imposed abduction
      adduction (AA) rotations effect was investigated on the estimators in two cases:
      when the estimators were trained on data without AA (Case 1) and with AA (Case
      2). The internal-external angle estimators showed high robustness to the imposed
      AA. The recorded errors for the best flexion-extension estimator were 0.9 degrees
      +/- 2.7 degrees  for Case 1 and 0.3 degrees  +/- 1.7 degrees  for Case 2. The
      proposed system has thus demonstrated its ability to accurately estimate
      concurrent flexion-extension and internal-external rotations.

PMID- 23962986
TI  - Multimodal deformable registration of traumatic brain injury MR volumes via the
      Bhattacharyya distance.
AB  - An important problem of neuroimaging data analysis for traumatic brain injury
      (TBI) is the task of coregistering MR volumes acquired using distinct sequences
      in the presence of widely variable pixel movements which are due to the presence
      and evolution of pathology. We are motivated by this problem to design a
      numerically stable registration algorithm which handles large deformations. To
      this end, we propose a new measure of probability distributions based on the
      Bhattacharyya distance, which is more stable than the widely used mutual
      information due to better behavior of the square root function than the logarithm
      at zero. Robustness is illustrated on two TBI patient datasets, each containing
      12 MR modalities. We implement our method on graphics processing units (GPU) so
      as to meet the clinical requirement of time-efficient processing of TBI data. We
      find that 6 sare required to register a pair of volumes with matrix sizes of 256
      * 256 * 60 on the GPU. In addition to exceptional time efficiency via its GPU
      implementation, this methodology provides a clinically informative method for the
      mapping and evaluation of anatomical changes in TBI.

PMID- 23962987
TI  - Effect of Hypericum perforatum on different models of movement disorders in rats.
AB  - The effects of Hypericum perforatum, a plant with antidepressant action, were
      evaluated in models of abnormal movements in rats, brought about by
      administration of fluphenazine or reserpine. The number of vacuous chewing
      movements (VCMs) and locomotor activity (the number of crossings and rears in the
      open field test) were measured. In experiment 1, rats received a single
      administration of fluphenazine enanthate (25 mg/kg, intramuscular) and/or daily
      treatment with H. perforatum (300 mg/kg, in place of drinking water) for 7 days.
      Fluphenazine increased VCMs and decreased locomotor activity. H. perforatum had
      no effect on either the number of VCMs or the locomotor activity. In experiment
      2, rats received reserpine every 2 days for 6 days (0.5 mg/kg, subcutaneous)
      and/or H. perforatum (300 mg/kg, in place of drinking water) daily for 16 days
      beginning 10 days before the first administration of reserpine. Reserpine
      treatment increased VCMs and decreased locomotor activity. H. perforatum had no
      effect on either the number of VCMs or the number of rears but did prevent the
      effect of reserpine on the number of crossings. In conclusion, H. perforatum
      failed to protect against orofacial movements induced by fluphenazine or
      reserpine in rats. 

PMID- 23962988
TI  - Kinetics and thermodynamics of metal binding to the N-terminus of a human copper
      transporter, hCTR1.
AB  - The N-terminus of hCTR1 was demonstrated to bind three Cu(+) ions tightly (log K
      = 14.92) and reversibly via its Met-rich motifs. Ag(+) binds to the protein with
      the same stoichiometry but much lower affinities than Cu(+). The protein also
      coordinates two Cu(2+) ions through its ATCUN motif and His-rich motif with lower
      affinity. This study provides an insight into the selectivity of the transporter.

PMID- 23962989
TI  - Methallothionein-3 contributes to vascular endothelial growth factor induction in
      a mouse model of choroidal neovascularization.
AB  - In the present study, we investigated possible roles of the zinc (Zn)-binding
      protein metallothionein-3 (MT3) and cellular Zn in a mouse model of laser-induced
      choroidal neovascularization (CNV) using wild-type (WT) and MT3-knockout (KO)
      mice. Quantitative RT-PCR was used for the detection of MT3 mRNA. CNV was induced
      in mice between 8 and 12 weeks of age by disrupting the Bruch's membrane using an
      argon laser. Fundus photography and fluorescein angiography (FA) were performed 2
      weeks following laser photocoagulation. The possible connection between MT3 and
      vascular endothelial growth factor (VEGF) expression was explored by quantifying
      VEGF levels in WT and MT3-KO mouse retinas by enzyme-linked immunosorbent assay.
      The role of Zn in VEGF expression was tested in WT and MT3-KO cells treated with
      pyrithione, with or without additional Zn, using immunoblotting and fluorescence
      photomicrography. Following laser-treatment, MT3-KO mice exhibited substantially
      smaller areas of CNV compared to WT mice. In addition, retinal angiograms
      revealed less severe fluorescein leakage in MT3-KO mice than in WT mice. On day
      14 following the induction of CNV, VEGF expression was markedly increased in WT
      mice, but remained unchanged in MT3-KO mice. Consistent with the possible
      involvement of Zn released from MT3, raising intracellular Zn levels increased
      VEGF levels and activated its receptor, Flk-1, in both WT and MT3-KO retinal
      cells. Present results demonstrated that neural retinal cells express high levels
      of MT3, which might play a role in the process of CNV development. Moreover, Zn
      released from MT3 may contribute to VEGF induction. 

PMID- 23962990
TI  - Hospital readmission and parent perceptions of their child's hospital discharge.
AB  - OBJECTIVE: To describe parent perceptions of their child's hospital discharge and
      assess the relationship between these perceptions and hospital readmission.
      DESIGN: A prospective study of parents surveyed with questions adapted from the
      care transitions measure, an adult survey that assesses components of discharge
      care. Participant answers, scored on a 5-point Likert scale, were compared
      between children who did and did not experience a readmission using a Fisher's
      exact test and logistic regression that accounted for patient characteristics
      associated with increased readmission risk, including complex chronic condition
      and assistance with medical technology. SETTING: A tertiary-care children's
      hospital. PARTICIPANTS: A total of 348 parents surveyed following their child's
      hospital discharge between March and October 2010. INTERVENTION: None. MAIN
      OUTCOME MEASURE: Unplanned readmission within 30 days of discharge. RESULTS:
      There were 28 children (8.1%) who experienced a readmission. Children had a lower
      readmission rate (4.4 vs. 11.3%, P = 0.004) and lower adjusted readmission
      likelihood [odds ratio 0.2 (95% confidence interval 0.1, 0.6)] when their parents
      strongly agreed (n = 206) with the statement, 'I felt that my child was healthy
      enough to leave the hospital' from the index admission. Parent perceptions
      relating to care management responsibilities, medications, written discharge
      plan, warning signs and symptoms to watch for and primary care follow-up were not
      associated with readmission risk in multivariate analysis. CONCLUSIONS: Parent
      perception of their child's health at discharge was associated with the risk of a
      subsequent, unplanned readmission. Addressing concerns with this perception prior
      to hospital discharge may help mitigate readmission risk in children.

PMID- 23962991
TI  - Are the Dutch long-term care organizations getting better? A trend study of
      quality indicators between 2007 and 2009 and the patterns of regional influences
      on performance.
AB  - OBJECTIVE: and setting The Dutch long-term care organizations, providing somatic
      care, psycho-geriatric care and home care, have to measure the quality of care
      through client-related and professional indicators since 2007. At the same time,
      competition was introduced with regional stimuli from healthcare insurers. The
      first aim of this study is to determine the trends of the national performance on
      client-related and professional quality indicators for the period 2007-09 in long
      term care organizations in the Netherlands. The second aim is to determine the
      influence of the region on the quality performance in 2009. DESIGN AND
      PARTICIPANTS: We performed trend analyses on the indicators of clients of 2115
      long-term care organizations. We used multivariate analyses to determine the
      difference in national performance between 2007 and 2009 and to calculate the
      influence of the region on the performance of 2009. INTERVENTION: None. MAIN
      OUTCOME MEASURES: Client-related and professional indicators. RESULTS: The
      national performance on client-related indicators for somatic care and home care
      increased and for psycho-geriatric care the quality performance became worse. The
      professional indicators for intramural care improved between 2007 and 2009.
      Region influences the performance. In general, organizations in the west of the
      Netherlands performed worse than other regions (with exception of home care).
      CONCLUSIONS: The study suggests that working with quality indicators in long-term
      care organizations for older people may lead to a better performance on several
      indicators. The influence of the region on the quality is significant, which
      could be caused by Dutch healthcare insurers.

PMID- 23962992
TI  - Quality in practice: preventing and managing neonatal sepsis in Nicaragua.
AB  - QUALITY PROBLEM OR ISSUE: Incorrect and excessive diagnosis of newborn infections
      in Nicaragua caused overcrowding in the neonatal intensive care units and
      unnecessary hospitalization. INITIAL ASSESSMENT: A baseline study in nine
      hospitals found that none correctly utilized disinfectants, sterilization or hand
      hygiene and that diagnosis of neonatal sepsis was based primarily on clinical
      manifestations. CHOICE OF SOLUTION: In 2007, the Ministry of Health (MINSA), with
      Unites States Agency for the International Development technical assistance,
      began developing guidelines and implementing quality improvement in infection
      prevention and control to reduce neonatal infections. In a second intervention
      phase, the MINSA introduced an algorithm for correct identification of maternal
      risk factors and standardized laboratory tests for neonatal sepsis.
      IMPLEMENTATION: Interventions included developing national guidelines on correct
      use of disinfectants and hand hygiene; training medical staff on the guidelines;
      revising the basic medical supply list to support appropriate antisepsis;
      defining a package of diagnostic tests for neonatal sepsis and systematically
      measuring compliance with the new procedures. EVALUATION: The 18 hospitals
      achieved appropriate use of disinfectants in a 12-month period. In seven
      hospitals that introduced improvements in diagnosis and management of neonatal
      sepsis, application of the standardized laboratory package in suspected sepsis
      cases increased from 0% in April 2009 to 93% in July 2011, and the median
      incidence of neonatal sepsis was reduced by 67%. LESSONS LEARNED: The
      organizational changes implemented for the diagnosis and verification of neonatal
      sepsis led to a reduction in the newborn sepsis admissions and expenditures for
      antibiotics, allowing resources to be redirected to treating other critically ill
      newborns.

PMID- 23962993
TI  - Clinical evaluation of a neuroprotective drug in patients with cervical
      spondylotic myelopathy undergoing surgical treatment: design and rationale for
      the CSM-Protect trial.
AB  - STUDY DESIGN: Descriptive article and narrative review. OBJECTIVE: To explain the
      rationale and design of the cervical spondylotic myelopathy (CSM)-Protect
      clinical trial that aims to elucidate the efficacy and safety of riluzole in the
      context of CSM. SUMMARY OF BACKGROUND DATA: CSM is the most common cause of
      spinal cord-related dysfunction internationally. Although surgery is effective in
      preventing the progression of impairment, and in some cases improving functional
      outcomes, many patients continue to exhibit significant disability in the
      postoperative setting. Evidence from preclinical studies suggests that glutamate
      related excitotoxicity may contribute to the pathology of CSM and that
      administration of the sodium and glutamate-blocking medication riluzole, when
      combined with spinal cord decompression, may mitigate this effect and improve
      neurobehavioral outcomes. Although riluzole is FDA approved and has been shown to
      be safe and effective in the context of amyotrophic lateral sclerosis, its
      efficacy and safety in the context of CSM remain unknown. METHODS: Descriptive
      article with narrative review of the literature. RESULTS: In addition to
      providing pertinent preclinical background on the topic, this descriptive article
      and narrative review discusses the design and current status of an ongoing phase
      III randomized controlled trial evaluating the efficacy and safety of riluzole,
      combined with surgical decompression, in the treatment of CSM. CONCLUSION: On the
      basis of current projections, we estimate that the interim analysis for this
      study will take place in the spring of 2014, at which time an adaptive sample
      size adjustment may take place.

PMID- 23962994
TI  - Cervical spondylotic myelopathy: current state of the art and future directions.
AB  - STUDY DESIGN: Narrative overview of the focus issue on cervical spondylotic
      myelopathy (CSM). OBJECTIVE: To provide an introduction to this special focus
      issue of Spine journal that deals with CSM. SUMMARY OF BACKGROUND DATA: CSM is a
      progressive spine disease and the leading cause of spinal cord dysfunction
      worldwide. The shift in population demographics in many parts of the world has
      motivated the development of this focus issue. With the overall aging of the
      population, we can predict that global health care systems will be confronted
      with an increase in patients presenting with degenerative spine changes and
      various stages of cervical myelopathy. METHODS: The articles in this issue vary
      in their methods-there are systematic reviews, narrative reviews, a study
      protocol, and 2 primary research articles. RESULTS: A summary of the findings of
      each article is provided as a table within this introduction. CONCLUSION: By way
      of this issue, we have summarized current knowledge gaps and limitations in the
      evidence to provide direction for future research and investigation. These
      include the need for a unified nomenclature for referring to CSM, the need to
      specify the incidence of myelopathy and the prevalence of ossification of the
      posterior longitudinal ligament, and the need to explore both the safety and
      efficacy of neuroprotective and neuroreparative pharmacological strategies.
      Further work is also required to optimize the management of patients with minimal
      symptoms.

PMID- 23962995
TI  - Anterior versus posterior approach for treatment of cervical spondylotic
      myelopathy: a systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: We performed a systematic review to
      determine the comparative effectiveness and safety profiles of anterior versus
      posterior decompression procedures for multilevel cervical spondylotic myelopathy
      (CSM). SUMMARY OF BACKGROUND DATA: CSM is a common cause of neurological
      dysfunction. It is well established that surgical decompression of the cervical
      spinal cord is an effective treatment option for CSM. Because of the lack of well
      designed prospective studies, there remains a lack of consensus whether
      multilevel spondylotic compression is best treated via an anterior or posterior
      surgical route and whether one of these surgical approaches is superior in terms
      of patient outcomes and/or complication profiles. METHODS: We conducted a
      systematic search for literature published through September 2012. We sought to
      identify comparative studies (e.g., randomized controlled trials, cohort studies)
      comparing anterior with posterior procedures in patients with 2-level or greater
      cord compression resulting in CSM. Standardized mean differences were calculated
      to allow comparisons of the change (i.e., improvement or decline) in scores
      between anterior and posterior surgical procedures by study. Clinical
      recommendations were made through a modified Delphi approach by applying the
      GRADE (Grading of Recommendation Assessment, Development and Evaluation)/AHRQ
      (Agency for Healthcare Research and Quality) criteria. RESULTS: We identified 8
      level III retrospective cohort studies that met the inclusion criteria from a
      total of 135 possible studies for review. With regard to effectiveness between
      the 2 approaches, improvements in JOA (Japanese Orthopaedic Association) scores
      were similar, whereas canal diameter change was larger after posterior surgery.
      With regard to safety, postoperative C5 palsy rates were similar, infection rates
      were lower with anterior surgery, and dysphagia rates were lower with posterior
      surgery. CONCLUSION: This systematic review demonstrates that, for both
      effectiveness and safety, there is no clear advantage to either an anterior
      surgical approach or a posterior surgical approach when treating patients with
      multilevel CSM. With that, a surgical strategy developed on a patient-to-patient
      basis should be used to achieve optimal patient outcomes. In addition,
      development of a consensus for standardized reporting of outcome measures and
      complication profiles would facilitate improved comparisons across differing
      treatment centers and surgical techniques. EVIDENCE-BASED CLINICAL
      RECOMMENDATIONS: RECOMMENDATION: We recommend an individualized approach when
      treating patients with CSM accounting for pathoanatomical variations (ventral vs.
      dorsal, focal vs. diffuse, sagittal, dynamic instability) because there are
      similar outcomes between the anterior and posterior approaches with regard to
      effectiveness and safety. OVERALL STRENGTH OF EVIDENCE: Low. STRENGTH OF
      RECOMMENDATION: Strong.

PMID- 23962996
TI  - Systematic review of magnetic resonance imaging characteristics that affect
      treatment decision making and predict clinical outcome in patients with cervical
      spondylotic myelopathy.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To determine whether there are
      magnetic resonance imaging (MRI) characteristics in patients with cervical
      spondylotic myelopathy that affect treatment decisions or predict postsurgical
      outcomes or adverse events. SUMMARY OF BACKGROUND DATA: Although the role of MRI
      in confirming the clinical diagnosis of cervical spondylotic myelopathy and
      directing surgical management is well established, its potential value as a
      prognostic tool is largely unknown. METHODS: A systematic search was conducted
      using PubMed and the Cochrane Collaboration Library for articles published
      between January 1, 1956, and November 20, 2012. The overall body of evidence with
      respect to each clinical question was determined on the basis of precepts
      outlined by the Grading of Recommendation Assessment, Development and Evaluation
      Working Group and recommendations made by the Agency for Healthcare Research and
      Quality. RESULTS: The initial search yielded 268 citations. Twenty publications
      met all inclusion criteria and were included in the review. Three of these
      assessed MRI predictors of clinical deterioration in the case of conservative
      treatment and 17 evaluated MRI anatomic or cord characteristics that could
      predict surgical outcome or adverse events. There is low evidence suggesting that
      a high signal intensity (SI) grade on T2WI is not associated with patient
      deterioration during conservative treatment. High SI grade on T2WI, along with
      compression ratio and canal diameter, was not an important predictor of outcome.
      There is low evidence identifying number of high SI segments on T2WI, low SI
      segments on T1WI, combined T1/T2 SI, and SI ratio as important negative
      predictors of surgical outcome. CONCLUSION: On the basis of this review and on
      low-quality evidence, we have identified 3 important negative predictors of
      surgical outcome: number of high SI segments on T2WI, combined T1/T2 signal
      change, and SI ratio.EVIDENCE-BASED CLINICAL RECOMMENDATIONS: RECOMMENDATION 1:
      We suggest that when clinically feasible, surgeons rely on MRI to confirm the
      diagnosis of CSM and rely on clinical history and examination to determine
      progression and severity of disease. OVERALL STRENGTH OF EVIDENCE: Low. STRENGTH
      OF RECOMMENDATION: Weak. RECOMMENDATION 2: T2 signal may be a useful prognostic
      indicator when used in combination with low SI change on T1WI, or as a ratio
      comparing compressed with noncompressed segments, or as a ratio of T2 compared
      with T1WI. We suggest that if surgeons use MRI signal intensity to estimate the
      risk of a poor outcome after surgery, they use high SI change on T2WI in
      combination with other signal intensity parameters, and not in isolation. OVERALL
      STRENGTH OF EVIDENCE: Low. StrENGTH OF RECOMMENDATION: Weak.

PMID- 23962997
TI  - Differential diagnosis for cervical spondylotic myelopathy: literature review.
AB  - STUDY DESIGN: Literature review. OBJECTIVE: To identify case series that have
      been confused with cervical spondylotic myelopathy (CSM) to develop a
      comprehensive differential diagnosis. SUMMARY OF BACKGROUND DATA: Myelopathy can
      be caused by a number of different etiologies. In those patients with CSM, the
      presentation is not always clear. Distinct radiographical and clinical
      characteristics, which are not always obvious, aid in arriving at the correct
      diagnosis. METHODS: A PubMed search was done to identify reports written in
      English describing conditions that may present in a manner similar to CSM to
      differentiate them from CSM. Material from review articles and relevant textbooks
      was also considered. Information regarding the number of patients, the specific
      diagnosis presenting as myelopathy, the diagnostic findings, and the method(s)
      for distinguishing CSM from the initial diagnosis was abstracted from included
      articles. Salient features of the conditions were summarized. RESULTS: A total of
      35 citations (totaling 474 patients) that reported on diagnoses confused with CSM
      based on clinical presentation were included. All were case reports or small case
      series. The differential diagnoses were organized into 7 categories:
      congenital/anatomic, degenerative, neoplastic, inflammatory/autoimmune,
      idiopathic, circulatory, and metabolic. The primary conditions in the
      differential included amyotrophic lateral sclerosis, multiple sclerosis,
      syringomyelia, and spinal tumors. CONCLUSION: In the vast majority of cases,
      magnetic resonance imaging was an invaluable tool in determining the correct
      diagnosis. Electrodiagnostic studies, cerebrospinal fluid profile, unique
      symptomatology, and consideration of patient demographics can also aid in the
      diagnosis. Bilateral sensory complaints in the hands are suspicious for cervical
      cord pathology and MR imaging of the same should be done even if the
      electromyography/nerve conduction studies (NCS) suggest bilateral carpal tunnel
      syndrome. SUMMARY STATEMENTS: Physical exam findings are not always consistent
      with severity of disease in CSM; therefore, correlation to plain radiographs,
      MRI, and patient symptomatology is essential for arriving at the correct
      diagnosis. In some cases where these studies are still equivocal, use of other
      studies should be considered including electrodiagnostic studies as well as
      cerebrospinal fluid examination.

PMID- 23962998
TI  - Comparison of anterior surgical options for the treatment of multilevel cervical
      spondylotic myelopathy: a systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: The primary objectives of this review
      were to compare the effectiveness and safety of various anterior cervical
      decompressive and reconstructive procedures for diffuse or multifocal cervical
      spondylotic myelopathy (CSM). An additional objective was to describe the most
      common ancillary stabilization techniques used with the different anterior
      decompressive procedures. SUMMARY OF BACKGROUND DATA: Surgical management of CSM
      provides for neurological recovery and disease stabilization in a cost-effective
      way. Although both retrospective and prospective data support management of CSM
      by anterior cervical decompression and fusion, the choice decision between
      various anterior surgical options remains unclear. METHODS: We conducted a
      systematic search in MEDLINE and the Cochrane Collaboration Library for human
      studies in the English-language literature published through September 2012. We
      included studies comparing multiple discectomies with single or multiple
      corpectomy, multiple discectomies with discectomy-corpectomy hybrid, and multiple
      corpectomies with discectomy-corpectomy hybrid, comparing effectiveness and
      safety outcomes of each procedure, and defining the ancillary stabilization
      techniques used. Exclusion criteria included patients with degenerative disc
      disease or degenerative joint disease without CSM, single-level CSM, ossified
      posterior longitudinal ligament (OPLL), spinal tumor, concomitant infection, and
      ankylozing spondylitis. Case series, case reports, data not reported separately
      for each comparison group, or studies that consisted of an N less than 10 for
      either comparison group were excluded. The evidence strength was rated using the
      GRADE (Grades of Recommendation Assessment, Development, and Evaluation)
      criteria. RESULTS: Of the 49 citations identified from our search, 10 studies
      were initially found suitable for inclusion. Patients undergoing any of the 3
      procedures generally experienced improvements in clinical outcomes (neck
      disability index, Japanese Orthopaedic Association score, and Visual Analogue
      Scale score for pain) as well as overall sagittal alignment, with minimal
      perioperative morbidity. There is moderate evidence supporting selection of
      multiple discectomies compared with corpectomy or discectomy-corpectomy hybrid
      procedures with regard to superior clinical outcomes and postoperative sagittal
      alignment. Furthermore, if more extensive operation is needed, there is evidence
      to support the selection of discectomy-corpectomy hybrid procedures compared with
      multiple corpectomies if it is technically feasible to accomplish the requisite
      decompression. The multiple discectomies approach also may have a lower incidence
      of C5 palsy than corpectomy or discectomy-corpectomy hybrid approaches.
      CONCLUSION: All 3 operative approaches are effective strategies for the anterior
      surgical management of CSM. When the patient pathoanatomy permits, selection of
      multiple discectomies is favored compared with corpectomy or discectomy
      corpectomy hybrid approaches. EVIDENCE-BASED CLINICAL RECOMMENDATIONS:
      RECOMMENDATION 1: When pathoanatomically appropriate with minimal retrovertebral
      disease, we recommend the selection of multiple discectomy over corpectomy or
      discectomy-corpectomy hybrid procedures. OVERALL STRENGTH OF EVIDENCE: Low.
      STRENGTH OF RECOMMENDATION: Strong. RECOMMENDATION 2: When retrovertebral disease
      is significant, we recommend, when possible, that discectomy-corpectomy hybrid
      procedures be performed instead of multiple corpectomies. OVERALL STRENGTH OF
      EVIDENCE: Moderate. STRENGTH OF RECOMMENDATION: Strong. SUMMARY STATEMENTS: There
      is no evidence to guide choice of ancillary external immobilization techniques
      following multilevel anterior decompression and fusion procedures for CSM.

PMID- 23962999
TI  - Predictive factors affecting outcome after cervical laminoplasty.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To determine whether various
      preoperative factors affect patient outcome after cervical laminoplasty for
      cervical spondylotic myelopathy (CSM) and/or ossification of posterior
      longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: Cervical laminoplasty
      is a procedure designed to decompress the spinal cord by enlarging the spinal
      canal while preserving the lamina. Prior research has identified a variety of
      potential predictive factors that might affect outcomes after this procedure.
      METHODS: A systematic search of multiple major medical reference databases was
      conducted to identify studies explicitly designed to evaluate the effect of
      preoperative factors on patient outcome after cervical laminoplasty for CSM or
      OPLL. Studies specifically designed to evaluate potential predictive factors and
      their associations with outcome were included. Only cohort studies that used
      multivariate analysis, enrolled at least 20 patients, and adjusted for age as a
      potential confounding variable were included. JOA (Japanese Orthopaedic
      Association), modified JOA, and JOACMEQ-L (JOA Cervical Myelopathy Evaluation
      Questionnaire lower extremity function section) scores were the main outcome
      measures. Clinical recommendations and consensus statements were made through a
      modified Delphi approach by applying the GRADE (Grading of Recommendation
      Assessment, Development and Evaluation)/AHRQ (Agency for Healthcare Research and
      Quality) criteria. RESULTS: The search strategy yielded 433 citations, of which 1
      prospective and 11 retrospective cohort studies met our inclusion criteria.
      Overall, the strength of evidence from the 12 studies is low or insufficient for
      most of the predictive factors. Increased age was not associated with poorer JOA
      outcomes for patients with CSM, but there is insufficient evidence to make a
      conclusion for patients with OPLL. Increased severity of disease and a longer
      duration of symptoms might be associated with JOA outcomes for patients with CSM.
      Hill-shaped lesions might be associated with poorer JOA outcomes for patients
      with OPLL. There is insufficient evidence to permit conclusions regarding other
      predictive factors. CONCLUSION: Overall, the strength of evidence for all of the
      predictive factors was insufficient or low. Given that cervical myelopathy due to
      CSM tends to be progressive and that increased severity of myelopathy and
      duration of symptoms might be associated with poorer outcomes after cervical
      laminoplasty for CSM, it is preferable to perform laminoplasty in patients with
      CSM earlier rather than waiting for symptoms to get worse. Further research is
      needed to more clearly identify predictive factors that affect outcomes after
      cervical laminoplasty because there were relatively few studies identified that
      used multivariate analyses to control for confounding factors and many of these
      studies did not provide a detailed description of the multivariate analyses or
      the magnitude of effect estimates. EVIDENCE-BASED CLINICAL RECOMMENDATIONS:
      RECOMMENDATION 1: For patients with CSM, increased age is not a strong predictor
      of clinical neurological outcomes after laminoplasty; therefore, age by itself
      should not preclude cervical laminoplasty for CSM. OVERALL STRENGTH OF EVIDENCE:
      Low. STRENGTH OF RECOMMENDATION: Strong. RECOMMENDATION 2: For patients with CSM,
      increased severity of disease and a longer duration of symptoms might be
      associated with poorer clinical neurological outcomes after laminoplasty;
      therefore, we recommend that patients be informed about this. OVERALL STRENGTH OF
      EVIDENCE: Low. STRENGTH OF RECOMMENDATION: Strong. SUMMARY STATEMENTS: For
      patients with OPLL, hill-shaped lesions might be associated with poorer clinical
      neurological outcomes after laminoplasty; therefore, surgeons might consider
      potential benefits and risks of alternative or additional surgery.

PMID- 23963000
TI  - Outcomes after laminoplasty compared with laminectomy and fusion in patients with
      cervical myelopathy: a systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To determine the effectiveness and
      safety of cervical laminoplasty versus laminectomy and fusion for the treatment
      of cervical myelopathy, and to identify any patient subgroups for whom one
      treatment may result in better outcomes than the other. SUMMARY OF BACKGROUND
      DATA: Cervical laminoplasty and cervical laminectomy plus fusion are both
      procedures that treat cervical stenosis induced myelopathy by expanding the space
      available for the spinal cord. Although there are strong proponents of each
      procedure, the effectiveness, safety, and differential effectiveness and safety
      of laminoplasty versus laminectomy and fusion remains unclear. METHODS: A
      systematic search of multiple major medical reference databases was conducted to
      identify studies that compared laminoplasty with laminectomy and fusion. Studies
      could include either or both cervical myelopathic spondylosis (CSM) and
      ossification of the posterior longitudinal ligament. Randomized controlled trials
      and cohort studies were included. Case reports and studies with less than 10
      patients in the comparative group were excluded. Japanese Orthopaedic
      Association, modified Japanese Orthopaedic Association, and Nurick scores were
      the primary outcomes measuring myelopathy effectiveness. Reoperation and
      complication rates were evaluated for safety. Clinical recommendations were made
      through a modified Delphi approach by applying the Grading of Recommendations
      Assessment, Development and Evaluation/Agency for Healthcare Research and Quality
      criteria. RESULTS: The search strategy yielded 305 citations, and 4 retrospective
      cohort studies ultimately met our inclusion criteria. For patients with CSM, data
      from 3 class of evidence III retrospective cohort studies suggest that there is
      no difference between treatment groups in severity of myelopathy or pain: 2
      studies reported no significant difference between treatment groups in severity
      of myelopathy, and 3 studies found no significant difference in pain outcomes
      between treatment groups. For patients with ossification of the posterior
      longitudinal ligament, one small class of evidence III retrospective cohort study
      reported significant improvements in myelopathy severity after laminectomy and
      fusion compared with laminoplasty, but no differences in long-term pain between
      treatment groups. The overall evidence on the comparative safety of laminoplasty
      compared with laminectomy and fusion is inconsistent. Reoperation rates were
      lower after laminoplasty in 2 of 3 studies reporting. However, the incidence of
      debilitating neck pain was higher after laminoplasty as reported by one study;
      results on neurological complications were inconclusive, with 2 studies
      reporting. Results on kyphotic deformity were inconsistent, with opposite results
      in the 2 studies reporting. After laminectomy and fusion, 1% to 38% of patients
      had pseudarthrosis. Infection rates were slightly lower after laminoplasty, but
      the results are not likely to be statistically significant. CONCLUSION: For
      patients with CSM, there is low-quality evidence that suggests that laminoplasty
      and laminectomy and fusion procedures are similarly effective in treating CSM.
      For patients with ossification of the posterior longitudinal ligament, the
      evidence regarding the effectiveness of these procedures is insufficient. For
      both patient populations, the evidence as to whether one procedure is safer than
      the other is insufficient. Higher-quality research is necessary to more clearly
      delineate when one procedure is preferred compared with the other. EVIDENCE-BASED
      CLINICAL RECOMMENDATIONS: RECOMMENDATION: For CSM, evidence suggests that
      laminoplasty and laminectomy-fusion procedures can be similarly effective. We
      suggest that surgeons consider each case individually and take into account their
      own familiarity and expertise with each procedure. OVERALL STRENGTH OF EVIDENCE:
      Low. STRENGTH OF RECOMMENDATION: Weak.

PMID- 23963001
TI  - Association of myelopathy scores with cervical sagittal balance and normalized
      spinal cord volume: analysis of 56 preoperative cases from the AOSpine North
      America Myelopathy study.
AB  - STUDY DESIGN: Post hoc analysis of prospectively collected data. OBJECTIVE:
      Development of methods to determine in vivo spinal cord dimensions and
      application to correlate preoperative alignment, myelopathy, and health-related
      quality-of-life scores in patients with cervical spondylotic myelopathy (CSM).
      SUMMARY OF BACKGROUND DATA: CSM is the leading cause of spinal cord dysfunction.
      The association between cervical alignment, sagittal balance, and myelopathy has
      not been well characterized. METHODS: This was a post hoc analysis of the
      prospective, multicenter AOSpine North America CSM study. Inclusion criteria for
      this study required preoperative cervical magnetic resonance imaging (MRI) and
      neutral sagittal cervical radiography. Techniques for MRI assessment of spinal
      cord dimensions were developed. Correlations between imaging and health-related
      quality-of-life scores were assessed. RESULTS: Fifty-six patients met inclusion
      criteria (mean age = 55.4 yr). The modified Japanese Orthopedic Association
      (mJOA) scores correlated with C2-C7 sagittal vertical axis (SVA) (r = -0.282, P =
      0.035). Spinal cord volume correlated with cord length (r = 0.472, P < 0.001) and
      cord average cross-sectional area (r = 0.957, P < 0.001). For all patients, no
      correlations were found between MRI measurements of spinal cord length, volume,
      mean cross-sectional area or surface area, and outcomes. For patients with
      cervical lordosis, mJOA scores correlated positively with cord volume (r = 0.366,
      P = 0.022), external cord area (r = 0.399, P = 0.012), and mean cross-sectional
      cord area (r = 0.345, P = 0.031). In contrast, for patients with cervical
      kyphosis, mJOA scores correlated negatively with cord volume (r = -0.496, P =
      0.043) and mean cross-sectional cord area (r = -0.535, P = 0.027). CONCLUSION:
      This study is the first to correlate cervical sagittal balance (C2-C7 SVA) to
      myelopathy severity. We found a moderate negative correlation in kyphotic
      patients of cord volume and cross-sectional area to mJOA scores. The opposite
      (positive correlation) was found for lordotic patients, suggesting a relationship
      of cord volume to myelopathy that differs on the basis of sagittal alignment. It
      is interesting to note that sagittal balance but not kyphosis is tied to
      myelopathy score. Future work will correlate alignment changes to cord morphology
      changes and myelopathy outcomes. SUMMARY STATEMENTS: This is the first study to
      correlate sagittal balance (C2-C7 SVA) to myelopathy severity. We found a
      moderate negative correlation in kyphotic patients of cord volume and cross
      sectional area to mJOA scores. The opposite (positive correlation) was found for
      lordotic patients, suggesting a relationship of cord volume to myelopathy that
      differs on the basis of sagittal alignment.

PMID- 23963002
TI  - Unknown case: part 1.

PMID- 23963003
TI  - Unknown case: part 2: Vertebral and spinal cord hydatidosis.

PMID- 23963004
TI  - Pathophysiology and natural history of cervical spondylotic myelopathy.
AB  - STUDY DESIGN: This study is a combination of narrative and systematic review.
      OBJECTIVE: Clinicians who deal with cervical spondylotic myelopathy (CSM) should
      be up-to-date with the emerging knowledge related to the cascade of
      pathobiological secondary events that take place under chronic cervical spinal
      cord compression. Moreover, by performing a systematic review, we aim to (1)
      describe the natural history and (2) determine potential risk factors that affect
      the progression of CSM. SUMMARY OF BACKGROUND DATA: The pathophysiology, natural
      history, as well as the factors associated with clinical deterioration have not
      been fully described in CSM. METHODS: For the first part of the study, a
      literature review was performed. To answer key questions 1 and 2 of the second
      goal, a systematic search was conducted in PubMed and the Cochrane Collaboration
      Library for articles published between January 1, 1956, and November 7, 2012. We
      included all articles that described the progression and outcomes of CSM for
      which no surgical intervention was given. RESULTS: By performing a narrative
      literature review, we found that the assumption that acute traumatic spinal cord
      injury and CSM share a similar series of cellular and molecular secondary injury
      events was made in the past. However, recent advances in basic research have
      shown that the chronic mechanical compression results in secondary injury
      mechanisms that have distinct characteristics regarding the nature and the
      temporal profile compared with those of spinal cord injury. For the purpose of
      the systematic review, 10 studies yielding 16 publications met inclusion criteria
      for key questions 2 and 3. Moderate-strength evidence related to the natural
      history of CSM suggests that 20% to 60% of patients will deteriorate
      neurologically over time without surgical intervention. Finally, there is low
      strength evidence indicating that the area of circumferential compression is
      associated with deteriorating neurological symptoms. CONCLUSION: CSM has unique
      pathobiological mechanisms that mainly remain unexplored. Although the natural
      history of CSM can be mixed, surgical intervention eliminates the chances of the
      neurological deterioration. EVIDENCE-BASED CLINICAL RECOMMENDATIONS:
      RECOMMENDATION: Evidence concerning the natural history of CSM suggests that 20%
      to 60% of patients will deteriorate neurologically over time without surgical
      intervention. Therefore, we recommend that patients with mild CSM be counseled
      regarding the natural history of CSM and have the option of surgical
      decompression explained. OVERALL STRENGTH OF EVIDENCE: Moderate. STRENGTH OF
      RECOMMENDATION: Strong. SUMMARY STATEMENTS: Chronic compression of the spinal
      cord results in progressive neural cell loss related to secondary mechanisms
      including apoptosis, neuroinflammation, and vascular disruption.

PMID- 23963005
TI  - Frequency, timing, and predictors of neurological dysfunction in the
      nonmyelopathic patient with cervical spinal cord compression, canal stenosis,
      and/or ossification of the posterior longitudinal ligament.
AB  - STUDY DESIGN: Systematic review and survey. OBJECTIVE: To perform an evidence
      synthesis of the literature and obtain information from the global spine care
      community assessing the frequency, timing, and predictors of symptom development
      in patients with radiographical evidence of cervical spinal cord compression,
      spinal canal narrowing, and/or ossification of posterior longitudinal ligament
      (OPLL) but no symptoms of myelopathy. SUMMARY OF BACKGROUND DATA: Evidence for a
      marker to predict symptom development remains sparse, and there is controversy
      surrounding the management of asymptomatic patients. METHODS: We conducted a
      systematic review of the English language literature and an international survey
      of spine surgeons to answer the following key questions in patients with
      radiographical evidence of cervical spinal cord compression, spinal canal
      narrowing, and/or OPLL but no symptoms of myelopathy: (1) What are the frequency
      and timing of symptom development? (2) What are the clinical, radiographical, and
      electrophysiological predictors of symptom development? (3) What clinical and/or
      radiographical features influence treatment decisions based on an international
      survey of spine care professionals? RESULTS: The initial literature search
      yielded 388 citations. Applying the inclusion/exclusion criteria narrowed this to
      5 articles. Two of these dealt with the same population. For patients with spinal
      cord compression secondary to spondylosis, one study reported the frequency of
      myelopathy development to be 22.6%. The presence of symptomatic radiculopathy,
      cervical cord hyperintensity on magnetic resonance imaging, and prolonged
      somatosensory- and motor-evoked potentials were reported in one study as
      significant independent predictors of myelopathy development. In contrast, the
      lack of magnetic resonance imaging hyperintensity was found to be a positive
      predictor of early myelopathy development (<= 12-mo follow-up). For subjects with
      OPLL, frequency of myelopathy development was reported in 3 articles and ranged
      from 0.0% to 61.5% of subjects. One of these studies reported canal stenosis of
      60% or more, lateral deviated OPLL, and increased cervical range of motion as
      significant predictors of myelopathy development. In a survey of 774 spine
      surgeons, the majority deemed the presence of clinically symptomatic
      radiculopathy to predict progression to myelopathy in nonmyelopathic patients
      with cervical stenosis. Survey responses pertaining to 3 patient case vignettes
      are also presented and discussed in the context of the current literature.
      CONCLUSION: On the basis of these results, we provide a series of evidence-based
      recommendations related to the frequency, timing, and predictors of myelopathy
      development in asymptomatic patients with cervical stenosis secondary to
      spondylosis or OPLL. Future prospective studies are required to refine our
      understanding of this topic. EVIDENCE-BASED CLINICAL RECOMMENDATIONS:
      RECOMMENDATION: Patients with cervical canal stenosis and cord compression
      secondary to spondylosis, without clinical evidence of myelopathy, and who
      present with clinical or electrophysiological evidence of cervical radicular
      dysfunction or central conduction deficits seem to be at higher risk for
      developing myelopathy and should be counseled to consider surgical treatment.
      OVERALL STRENGTH OF EVIDENCE: Moderate. STRENGTH OF RECOMMENDATION: Strong.
      SUMMARY STATEMENTS: STATEMENT 1: On the basis of the current literature, for
      patients with cervical canal stenosis and cord compression secondary to
      spondylosis, without clinical evidence of myelopathy, approximately 8% at 1-year
      follow-up and 23% at a median of 44-months follow-up develop clinical evidence of
      myelopathy. STATEMENT 2: For patients with cervical canal stenosis and cord
      compression secondary to spondylosis, without clinical evidence of myelopathy,
      the absence of magnetic resonance imaging intramedullary T2 hyperintensity has
      been shown to predict early myelopathy development (<12-mo follow-up) and the
      presence of such signal has been shown to predict late myelopathy development
      (mean 44-mo follow-up). In light of this discrepancy, no definite recommendation
      can be made surrounding the utility of this finding in predicting myelopathy
      development. STATEMENT 3: For patients with OPLL but without myelopathy, no
      recommendation can be made regarding the incidence or predictors of progression
      to myelopathy.

PMID- 23963006
TI  - Nonoperative management of cervical myelopathy: a systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To conduct a systematic review
      investigating the evidence of (1) efficacy, effectiveness, and safety of
      nonoperative treatment of patients with cervical myelopathy; (2) whether the
      severity of myelopathy affects outcomes of nonoperative treatment; and (3)
      whether specific activities or minor injuries are associated with neurological
      deterioration in patients with myelopathy or asymptomatic stenosis being treated
      nonoperatively. SUMMARY OF BACKGROUND DATA: Little is known about the appropriate
      role of nonoperative treatment in the management of cervical myelopathy, which is
      typically considered a surgical disorder. METHODS: A systematic search was
      conducted in PubMed and the Cochrane Collaboration Library for articles published
      between January 1, 1956, and November 20, 2012. We included all articles that
      compared nonoperative treatments or observation with surgery for patients with
      cervical myelopathy or asymptomatic cervical cord compression to determine their
      effects on clinical outcomes, including myelopathy scales (Japanese Orthopaedic
      Association, Nurick), general health scores (36-Item Short Form Health Survey),
      and pain (neck and arm). Nonoperative treatments included physical therapy,
      medications, injections, orthoses, and traction. We also searched for articles
      evaluating the effect of specific activities or minor trauma in neurological
      outcomes. Case reports and studies with less than 10 patients in the exposure
      group were excluded. RESULTS: Of 54 citations identified from our search, 5
      studies reported in 6 articles met inclusion criteria. In 1 randomized controlled
      study, there was low evidence that nonoperative treatment may yield equivalent or
      better outcomes than surgery in those with mild myelopathy. For moderate to
      severe myelopathy, nonoperative treatment had inferior outcomes versus surgery in
      2 cohort studies, despite the fact that surgically treated patients were worse at
      baseline. There was insufficient evidence to determine whether specific
      activities or minor trauma is a risk factor for neurological deterioration in
      those with myelopathy or asymptomatic cord compression. CONCLUSION: There is a
      paucity of evidence for nonoperative treatment of cervical myelopathy, and
      further studies are needed to determine its role more definitively. In
      particular, for the patient with milder degrees of myelopathy, randomized studies
      comparing nonoperative with surgical treatment would be particularly helpful, as
      would trials comparing specific types of nonoperative treatments with the natural
      history of myelopathy. EVIDENCE-BASED CLINICAL RECOMMENDATIONS: RECOMMENDATION 1:
      Because myelopathy is known to be a typically progressive disorder and there is
      little evidence that nonoperative treatment halts or reverses its progression, we
      recommend not routinely prescribing nonoperative treatment as the primary
      modality in patients with moderate to severe myelopathy. OVERALL STRENGTH OF
      EVIDENCE: Low. STRENGTH OF RECOMMENDATION: Strong. RECOMMENDATION 2: If there is
      a role for nonoperative treatment as a primary treatment modality, it may be in
      the patient with mild myelopathy. However, it is not clear which specific forms
      of nonoperative treatment provide any benefit compared with the natural history.
      If nonoperative treatment is selected, we suggest care be taken to observe for
      neurological deterioration. OVERALL STRENGTH OF EVIDENCE: Low. STRENGTH OF
      RECOMMENDATION: Weak. RECOMMENDATION 3: In those with asymptomatic spondylotic
      cord compression but no clinical myelopathy, the available literature neither
      supports nor refutes the notion that minor trauma is a risk factor for
      neurological deterioration. We suggest that patients should be counseled about
      this uncertainty. OVERALL STRENGTH OF EVIDENCE: Low. STRENGTH OF RECOMMENDATION:
      Weak. Recommendation 4: In those with a clinical diagnosis of cervical
      spondylotic myelopathy but no ossification of the posterior longitudinal
      ligament, the available studies did not specifically address the issue of
      neurological deterioration secondary to minor trauma. However, in those with
      underlying ossification of the posterior longitudinal ligament, trauma may be
      more likely to cause worsening of existing myelopathy or even initiate symptoms
      in those who were previously asymptomatic. We suggest that patients should be
      counseled about these possibilities. OVERALL STRENGTH OF EVIDENCE: Low. STRENGTH
      OF RECOMMENDATION: Weak.

PMID- 23963008
TI  - Genetics and heritability of cervical spondylotic myelopathy and ossification of
      the posterior longitudinal ligament: results of a systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To answer the following 3 clinical
      questions: (1) What is the evidence supporting a heritable predisposition for
      cervical spondylotic myelopathy (CSM) and ossification of the posterior
      longitudinal ligament (OPLL)? (2) What specific genetic polymorphisms have been
      associated with CSM and OPLL? (3) What is the evidence supporting a genetic basis
      for predicting postoperative outcomes for patients with CSM and OPLL? SUMMARY OF
      BACKGROUND DATA: OPLL and CSM are thought to be multifactorial conditions
      resulting from a combination of environmental and genetic factors. METHODS: A
      systematic review of the English language literature was undertaken for articles
      published between 1980 and November 7, 2012. The strength of evidence was
      determined by 2 independent reviewers using the Grading of Recommendation
      Assessment, Development and Evaluation (GRADE) criteria for studies addressing
      the first question of heritability and using the criteria set forth by the
      HuGENet Working Group in the Venice Interim Guidelines to address the last 2
      questions of genetic association. RESULTS: Of the 118 citations identified
      through the initial literature search, a total of 23 articles remained after
      application of inclusion/exclusion criteria. The 3 family association studies
      related to question 1 supported the principle of an inherited predisposition to
      CSM and OPLL; however, the strength of evidence supporting these findings was
      low. Within the 19 case-control studies related to question 2, 2 single
      nucleotide polymorphisms (COL6A1/Intron 32(-29) and COL11A2/Intron 6(-4)) were
      observed at higher frequencies in OPLL cases than in controls in more than 1
      study and may be associated with its development. There was insufficient evidence
      to support an association between CSM and any specific single nucleotide
      polymorphism or haplotype or to support the association of specific gene alleles
      with postoperative CSM outcomes. CONCLUSION: Existing family studies provide
      support for the principle of an inherited predisposition to CSM and OPLL.
      Multiple studies support the association of 2 collagen gene related single
      nucleotide polymorphisms with OPLL; however, there is insufficient evidence to
      support the association between CSM and any genetic polymorphism or to support a
      genetic predictor of surgical outcome. SUMMARY STATEMENTS: STATEMENT 1: Existing
      family studies provide support for the principle of an inherited predisposition
      to CSM and OPLL. STATEMENT 2: Two SNPs related to the collagen 6A1 gene
      (COL6A1/Intron 32(-29)) and the collagen 11A2 gene (COL11A2/Intron 6(-4)) have
      been associated with OPLL in multiple studies and may be associated with its
      development. STATEMENT 3: No statement can be made from the literature regarding
      the association of specific SNPs or haplotypes with CSM. STATEMENT 4: No
      statement can be made from the literature regarding genetic predictors of
      surgical outcome in the context of OPLL or CSM.

PMID- 23963009
TI  - Ancillary outcome measures for assessment of individuals with cervical
      spondylotic myelopathy.
AB  - STUDY DESIGN: Narrative review. OBJECTIVE: To identify suitable outcome measures
      that can be used to quantify neurological and functional impairment in the
      management of cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA:
      CSM is the leading cause of acquired spinal cord disability, causing varying
      degrees of neurological impairment which impact on independence and quality of
      life. Because this impairment can have a heterogeneous presentation, a single
      outcome measure cannot define the broad range of deficits seen in this
      population. Therefore, it is necessary to define outcome measures that
      characterize the deficits with greater validity and sensitivity. METHODS: This
      review was conducted in 3 stages. Stage I: To evaluate the current use of outcome
      measures in CSM, PubMed was searched using the name of the outcome measure and
      the common abbreviation combined with "CSM" or "myelopathy." Stage II: Having
      identified a lack of appropriate outcome measures, we constructed criteria by
      which measures appropriate for assessing the various aspects of CSM could be
      identified. Stage III: A second literature search was then conducted looking at
      specified outcomes that met these criteria. All literature was reviewed to
      determine specificity and psychometric properties of outcomes for CSM. RESULTS:
      Nurick grade, modified Japanese Orthopaedic Association Scale, visual analogue
      scale (VAS) for pain, Short Form (36) Health Survey (SF-36), and Neck Disability
      Index were the most commonly cited measures. The Short-Form 36 Health Survey and
      Myelopathy Disability Index have been validated in the CSM population with
      multiple studies, whereas the modified Japanese Orthopaedic Association Scale
      score, Nurick grade, and European Myelopathy Scale each had only one study
      assessing psychometric characteristics. No validity, reliability, or
      responsiveness studies were found for the VAS or Neck Disability Index in the CSM
      population. CONCLUSION: We recommend that the modified Japanese Orthopaedic
      Association Scale, Nurick grade, Myelopathy Disability Index, Neck Disability
      Index, and 30-Meter Walk Test are most appropriate for the assessment of CSM.
      However, 6 additional outcome measures (QuickDASH, Berg Balance Scale, Graded
      Redefined Assessment of Strength Sensibility and Prehension, Grip Dynamometer,
      and GAITRite Analysis) were identified, which provide complementary assessments
      for CSM. SUMMARY STATEMENTS: There does not exist a single or composite of
      outcome instruments that measures myelopathy impairment, function/disability, and
      participation that have also demonstrated reliability, validity, and
      responsiveness in a CSM population. More work in the development and psychometric
      evaluation of new or existing measures is necessary to identify the ideal
      composite of measures to be used in the clinical and research settings. The mJOA,
      Nurick grade, NDI, MDI, and 30MWT should be adopted in any clinical practice that
      treats CSM both for screening and clinical follow-up. We propose that clinicians
      and researchers consider using the ancillary measures identified, such as the
      QuickDASH, Berg Balance Scale, GRASSP version 1.0, Grip Strength, and GAITRite
      Analysis. It is highly recommended that baseline and follow-up measurements
      should be performed in patients with CSM.

PMID- 23963010
TI  - Diagnosis, heritability, and outcome assessment in cervical myelopathy: a
      consensus statement.
AB  - This section of the cervical spondylotic myelopathy (CSM) Spine focus issue
      collates evidence related to diagnosis, outcome assessment, and genetics. Given
      that a variety of different disease states can present similarly, a guide for
      diagnosing and differentiating CSM from other neurological conditions is
      initially presented. Although the value of magnetic resonance imaging in
      diagnosing CSM is cemented, its value as a tool to predict future outcome is less
      well established. To this end, the existing evidence suggests that although
      increased T2 cord signal is of limited value, the pairing of high T2 signal with
      low T1 signal, or a high T2 to T1 signal ratio, is associated with a reduced
      potential for neurological recovery at follow-up. Outcome assessment in CSM is of
      paramount importance when monitoring patients' clinical course or measuring the
      efficacy of therapeutic interventions. Here, the main outcome measures that have
      been used to assess patients with CSM are reviewed. At present, we recommend that
      clinicians acquire the modified Japanese Orthopaedic Association scale score and
      the Neck Disability Index on all patients with CSM at presentation and follow-up.
      Finally, in regard to genetics, the existing evidence seems to support the
      principle of an inherited predisposition to both CSM and ossification of the
      posterior longitudinal ligament. Although several genetic polymorphisms have been
      consistently associated with ossification of the posterior longitudinal ligament,
      no specific polymorphisms were consistently associated with CSM. 

PMID- 23963011
TI  - Symptomatic progression of cervical myelopathy and the role of nonsurgical
      management: a consensus statement.
AB  - This section of the cervical spondylotic myelopathy Spine focus issue collates
      the existing evidence related to natural history and nonoperative management. In
      the case of patients with symptomatic cervical spondylotic myelopathy treated
      nonoperatively, while 20% to 62% will deteriorate at 3 to 6 years of follow-up,
      no specific patient or disease characteristics have been shown to predict this
      change reliably. For patients without myelopathy with spondylotic cord
      compression, the rate of myelopathy development is approximately 8% at 1 year and
      approximately 23% at 4 years of follow-up. Clinical and/or electrophysiological
      evidence of cervical radiculopathy has been shown to predict such progression and
      should prompt strong consideration of surgical decompression. With respect to
      nonoperative care, in the case of mild myelopathy, there is low evidence that
      such treatment may have a role; for moderate and severe myelopathy, this
      treatment results in outcomes inferior to those of surgery and is not
      recommended. Given the unpredictably progressive nature of cervical myelopathy,
      the indications for nonoperative management are ostensibly limited. Finally, the
      preclinical rationale and clinical translation of a putative neuroprotective
      drug, which may one day serve to augment the effects of surgery in the treatment
      of cervical spondylotic myelopathy, is presented and discussed. 

PMID- 23963012
TI  - Surgical management of degenerative cervical myelopathy: a consensus statement.
AB  - Degenerative cervical myelopathy (DCM), including cervical spondylotic myelopathy
      and ossification of the posterior longitudinal ligament, presents a heterogeneous
      set of variables reflecting its complex nature. Multiple studies in the past have
      attempted to elucidate an ideal surgical algorithm that surgeons may use when
      treating these patients, unfortunately all studies to date, including the
      rigorous systematic review used in this focus issue, have fallen short in
      identifying a superior approach when addressing DCM. Likely because of a superior
      approach being nonexistent because there are multiple pathoanatomical
      considerations. In addition to the multitude of variables that spine surgeons
      face when deciding the treatment options for patients with DCM, the previous
      studies that have been published, unfortunately, lack in consistent outcome and
      complication reporting. Therefore, synthesizing a treatment algorithm remains
      difficult, however, the articles in this focus issue use the GRADE system to
      assess the overall quality (strength) of available evidence and, where
      appropriate, formulate evidence-based recommendations. Factors that should be
      included in surgical decision making are the sagittal alignment, anatomical
      location of the compressive pathology, number of levels of compression, presence
      of absence or instability or subluxation, the type compressive pathology (e.g.,
      spondylosis vs. ossification of the posterior longitudinal ligament), neck
      anatomy, bone quality, and surgeon experience or preference. Fortunately, as
      reviewed in the accompanying articles, a number of excellent surgical options
      exist that can be selected on the basis of the aforementioned pathoanatomical
      considerations.

PMID- 23963013
TI  - Myelopathy and spinal deformity: relevance of spinal alignment in planning
      surgical intervention for degenerative cervical myelopathy.
AB  - Surgical management of degenerative cervical myelopathy requires careful
      pathoanatomic consideration to select between various surgical options from both
      anterior and posterior approach. Hitherto, unexplored is the relevance of
      cervical deformity to the pathophysiology of such neurological disability, and
      whether correction of that deformity should be a surgical objective when planning
      for reconstruction after spinal cord decompression. Such correction could address
      both the static cord compression and the dynamic repetitive cord injury, while
      also restoring more normal biomechanics to the cervical spine. The articles in
      this focus issue's section on cervical spinal deformity reveal that cervical
      sagittal alignment is geometrically related to thoracolumbar spinal pelvic
      alignment and to T1 slope, and that it is further clinically correlated to
      regional disability and general health scores and to myelopathy severity. These
      conclusions are based on narrative reviews and a selection of primary research
      data, reflecting the nascency of this field. They further recommend for
      preoperative assessment of spinal alignment when significant deformity is
      suspected, and that correction of cervical kyphosis should be an objective when
      surgery is planned. 

PMID- 23963014
TI  - Utility of postoperative radiographs after anterior lumbar interbody fusion with
      or without posterior instrumentation.
AB  - STUDY DESIGN: Retrospective clinical and radiographical review. OBJECTIVE: To
      evaluate the utility of plain radiographical surveillance after anterior lumbar
      interbody fusion and determine to what extent radiographical findings affect
      postoperative decision making. SUMMARY OF BACKGROUND DATA: Postoperative
      radiographical surveillance is a ubiquitous practice among spine surgeons, which
      lacks evidence and has received growing attention in an environment of increasing
      health care cost and receding resources. Lumbar interbody fusions are being
      performed with increasing frequency from numerous approaches; nonetheless, there
      are no evidence-based guidelines for postoperative radiographical evaluation of
      patients after these procedures. METHODS: One hundred forty-six consecutive
      patients who underwent anterior lumbar interbody fusion with or without short
      segment posterior fusion from 2008 to 2011 were reviewed. Exclusion criteria were
      less than 6 months of follow-up, prior surgery, hybrid constructs with disc
      arthroplasty, and concurrent posterior fusion of greater than 3 levels. Three
      hundred fifty-nine radiographical series and 330 clinic notes of the included 67
      patients were reviewed. Radiographs were evaluated for abnormalities and clinic
      notes reviewed for any changes in clinical management by multiple reviewers.
      Interobserver reliability, sensitivity, specificity, and positive and negative
      predictive values were calculated. RESULTS: There was no single instance of a
      change in treatment course based on radiographical findings alone in any of the
      330 clinic visits of the 67 included patients during an average 15.8-month
      postoperative follow-up period. Thirty-four of the 67 patients (51%) had some
      change in their management on the basis of their clinical symptoms and/or
      examination. Interobserver agreement for change in management was 0.96 (kappa =
      0.918). Sensitivity (6%), specificity (97%), positive predictive value (67%), and
      negative predictive value (50%) were calculated. CONCLUSION: Routine
      postoperative radiographical surveillance has minimal value for asymptomatic
      patients after anterior lumbar interbody fusion with or without posterior fusion.
      Obtaining a limited number of postoperative films of these patients in the
      absence of clinical symptoms or risk factors could significantly reduce health
      care costs and unnecessary radiation exposure.

PMID- 23963015
TI  - Five-year outcomes of minimally invasive versus open transforaminal lumbar
      interbody fusion: a matched-pair comparison study.
AB  - STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE:
      To compare midterm clinical and radiological outcomes of minimally invasive
      surgery (MIS) versus open transforaminal lumbar interbody fusion (TLIF). SUMMARY
      OF BACKGROUND DATA: Open TLIF is a proven technique to achieve fusion in
      symptomatic spinal deformities and instabilities. The possible advantages of MIS
      TLIF include reduced blood loss, less pain, and shorter hospitalization. To date,
      there is no published data comparing their midterm outcomes. METHODS: From 2004
      2007, 40 cases of open TLIF were matched paired with 40 cases of MIS TLIF for
      age, sex, body mass index, and the levels on which the spine was operated.
      Oswestry Disability Index, neurogenic symptom score, the 36-Item Short Form
      Health Survey, and visual analogue scale scores for back and leg pain were
      obtained before surgery, 6 months, 2 years, and 5 years after surgery. Fusion
      rates were assessed using Bridwell classification. RESULTS: Fluoroscopic time
      (MIS: 55.2 s, open: 16.4 s, P < 0.001) was longer in MIS cases. Operative time
      (MIS: 185 min, open: 166 min, P = 0.085) was not significantly longer in MIS
      cases. MIS had less blood loss (127 mL) versus open (405 mL, P < 0.001)
      procedures. Morphine use for MIS cases (8.5 mg) was less compared with open (24.2
      mg, P = 0.006). Patients who underwent MIS (1.5 d) ambulated earlier than those
      who underwent open fusion (3 d, P < 0.001). Patients who underwent MIS (3.6 d)
      had shorter hospitalization than those who underwent open fusion (5.9 d, P <
      0.001). Both groups showed significant improvement in Oswestry Disability Index,
      neurogenic symptom score, back and leg pain, SF-36 scores at 6 months until 5
      years with no significant differences between them. Grade 1 fusion was achieved
      in 97.5% of both groups at 5 years. The overall complication rate was 20% for the
      open group and 15% for MIS group (P = 0.774), including 4 cases of adjacent
      segment disease for each group. CONCLUSION: MIS TLIF is comparable with open TLIF
      in terms of midterm clinical outcomes and fusion rates with the additional
      benefits of less initial postoperative pain, less blood loss, earlier
      rehabilitation, and shorter hospitalization.

PMID- 23963016
TI  - Application of the modified lower extremity functional scale in low back pain.
AB  - STUDY DESIGN: This was a cross-sectional study. OBJECTIVE: We sought to test the
      psychometric properties of the modified lower extremity functional scale (LEFS)
      for low back pain (LBP). SUMMARY OF BACKGROUND DATA: Low back and lower
      extremities are anatomically and functionally related, and radiating leg pain is
      common among patients with LBP. The LEFS is a reliable and valid questionnaire
      for patients with lower extremity conditions caused by musculoskeletal disorders,
      although its utility in LBP with or without radiating leg pain has not been
      tested. METHODS: We recruited subjects with LBP from physical medicine and
      rehabilitation outpatient clinics whose age was at least 18 years. The evaluation
      included demographic data, back pain history, pain intensity by the visual
      analogue scale, the Roland-Morris Disability Questionnaire, and the modified
      LEFS, in which "lower limb problem" was substituted with "low back/lower limb
      problem" in the introductory sentence of the questionnaire. Data from 242
      patients were analyzed for the psychometric properties of the modified LEFS,
      including floor and ceiling effects, internal consistency, test-retest
      reliability, dimensionality, and construct validity. RESULTS: The modified LEFS
      had no floor or ceiling effects, high internal consistency (Cronbach alpha:
      0.94), and good test-retest reliability (intraclass correlation coefficient[2,1]:
      0.86). Principal component analysis identified one major factor that had an
      eigenvalue of 9.9 and explained 49.6% of the total variance. The correlations
      between the modified LEFS and Roland-Morris Disability Questionnaire was high
      (Pearson correlation coefficient: -0.71). The modified LEFS also discriminated
      well between the subgroups of LBP with unilateral leg pain and those with
      bilateral leg pain. CONCLUSION: The modified LEFS had satisfactory psychometric
      properties in patients with LBP and could serve as a supplementary outcome
      measure to assess their activity limitations.

PMID- 23963017
TI  - Types and arrangement of thyroid shields to reduce exposure of surgeons to
      ionizing radiation during intraoperative use of C-arm fluoroscopy.
AB  - STUDY DESIGN: Measurement of radiation dose from C-arm fluoroscopy during a
      simulated intraoperative use in spine surgery. OBJECTIVE: To assess how the
      radiation dose is affected by changes in the types of thyroid shields used and by
      the arrangements or ways in which they are worn during the intraoperative use of
      C-arm fluoroscopy. SUMMARY OF BACKGROUND DATA: Although the danger to the thyroid
      from exposure to radiation is well known, there are no guidelines for the proper
      use of thyroid shields. METHODS: Two photoluminescence dosimeters were used to
      measure the dose of scattered radiation arriving at the location of the thyroid
      in a whole-body phantom in the position of the surgeon. On an operating table
      beside this setup was an anthropomorphic chest phantom representing a patient for
      which treatment with C-arm fluoroscopy was simulated. Radiation doses were
      measured using 3 different arrangements of the thyroid shield: worn tightly, worn
      loosely, and worn loosely with a bismuth masking reagent. The same tests were
      performed using 2 kinds of thyroid shield: lead and lead-equivalent. RESULTS: For
      the lead-shield group, radiation doses were measured in 3 arrangements; worn
      tightly, worn loosely, and worn loosely with a bismuth masking reagent, for which
      the results were 1.91 +/- 0.13, 2.35 +/- 0.22, and 1.86 +/- 0.13 MUSv/min,
      respectively. Wearing the shield tight against the throat and wearing it loose
      with a bismuth masking reagent led to lower radiation exposure levels than by
      simply wearing the shield loosely (P <= 0.001). For the lead-equivalent shield
      group, doses were measured for the same 3 arrangements, for which the results
      were 1.79 +/- 0.12, 1.82 +/- 0.11, and 1.74 +/- 0.12 MUSv/min. Lower scattered
      radiation doses were delivered to the thyroid in the lead-equivalent thyroid
      shield group compared with the lead thyroid shield group (P <= 0.001). The
      unshielded thyroid group received a radiation dose of 16.32 +/- 0.48 MUSv/min.
      CONCLUSION: The use of some form of thyroid shield is essential during the use of
      C-arm fluoroscopy. It was found that the best way to reduce scattered radiation
      exposure to the thyroid was wearing the thyroid shield tightly or wearing it
      loosely in combination with a bismuth masking reagent. LEVEL OF EVIDENCE: 2.

PMID- 23963018
TI  - Vertebral body stapling in children younger than 10 years with idiopathic
      scoliosis with curve magnitude of 30 degrees  to 39 degrees .
AB  - STUDY DESIGN: Dual-center, retrospective study. OBJECTIVE: To evaluate whether
      vertebral body stapling (VBS) influences curve progression between 30 degrees 
      and 39 degrees  in children younger than 10 years with idiopathic scoliosis.
      SUMMARY OF BACKGROUND DATA: Patients younger than 10 years with idiopathic
      scoliosis of more than 30 degrees  have a 100% risk of progression to spine
      fusion regardless of nonoperative treatment. VBS may represent an alternative
      fusionless treatment option for this group of high-risk patients. METHODS:
      Patients younger than 10 years with idiopathic thoracic or lumbar scoliosis of 30
      degrees  to 39 degrees  who were treated with VBS with a minimum of 24 months of
      follow-up were studied. Outcome variables were curve progression and magnitude,
      surgical complications, and a need for reoperation. Preoperative and
      postoperative curve magnitudes were compared using a paired Student t test.
      Postoperative curve magnitudes were compared with one another using a paired
      Student t test. A P value of less than 0.05 was defined as statistically
      significant. RESULTS: Twelve patients were studied (female: n = 12; average age:
      7.8 yr [range: 6.3-9.7 yr]). Thirteen curves were treated with VBS (thoracic: n =
      9; lumbar: n = 4). The average follow-up was 3.4 years (range: 2.2-5.4 yr). The
      average preoperative curve magnitude was 33.4 degrees  (range: 30 degrees -39
      degrees ). The immediate postoperative curve magnitude (19.0 degrees ; range: 0
      degrees -29 degrees ) and curve magnitude at the most recent follow-up (23.0
      degrees ; range: 10 degrees -34 degrees ) were significantly less than the
      preoperative magnitude of 33.4 degrees . Both thoracic curves (100%) and lumbar
      curves (100%) were treated successfully. Curve magnitudes did not change
      significantly postoperatively between the first erect radiographs and the most
      recent follow-up. Two patients had pneumothorax, and 1 patient had symptomatic
      pleural effusion. No patient required definitive fusion for curve progression.
      CONCLUSION: VBS is effective in controlling curve progression in the high-risk
      group of children younger than 10 years with idiopathic scoliosis between 30
      degrees  and 39 degrees  in whom bracing may be ineffective.

PMID- 23963019
TI  - Deep wound infections after spinal fusion in children with cerebral palsy: a
      prospective cohort study.
AB  - STUDY DESIGN: Prospective cohort. OBJECTIVE: To (1) calculate the rate of deep
      wound infection in children with cerebral palsy (CP) after spinal fusion surgery;
      (2) identify factors (patient, laboratory, and surgical) associated with deep
      wound infection development; and (3) report causative organisms. SUMMARY OF
      BACKGROUND DATA: Wound infection after spine fusion for CP is more common than
      after spine fusion for most other diagnoses. METHODS: We prospectively gathered
      data on 204 consecutive pediatric patients with CP who underwent surgery at 7
      institutions. Univariate and multivariate regression analysis was performed to
      analyze patient, laboratory, and surgical characteristics to identify factors
      that were significantly associated with infection development. Statistical
      significance was set at a value of P less than 0.05. RESULTS: Deep wound
      infection developed in 13 (6.4%) children. The mean time to infection development
      was 34.2 +/- 60.2 days. On univariate analysis, older age, larger curve size,
      presence of gastrostomy/gastrojejunostomy tube, higher preoperative serum white
      blood cell count, and longer operative time were significantly associated with
      deep wound infection. On multivariate analysis, only the presence of a
      gastrostomy/gastrojejunostomy tube remained significant (1.9-fold risk of deep
      wound infection compared with patients without tubes). Escherichia coli was the
      most common organism cultured from the wound sites (5 patients). Other infective
      agents were: Pseudomonas aeruginosa (2), methicillin-susceptible Staphylococcus
      aureus (1), Proteus mirabilis (1), and polymicrobial organisms (4). CONCLUSION:
      Deep wound infection occurred in 6.4% of children with CP after spinal fusion.
      The presence of a gastrostomy/gastrojejunostomy tube was a significant predictor
      of infection. Gram-negative organisms were the most common causative agents.
      Surgeons should be cognizant of these factors when treating children with CP and
      may consider Gram-negative antibiotic prophylaxis.

PMID- 23963020
TI  - Tumor necrosis factor-alpha-dependent infiltration of macrophages into the dorsal
      root ganglion in a rat disc herniation model.
AB  - STUDY DESIGN: A prospective molecular mechanism of macrophages infiltration in
      experimental disc herniation. OBJECTIVE: To investigate the mechanisms of
      macrophages infiltration into the dorsal root ganglion (DRG) in a rat model of
      disc herniation. SUMMARY OF BACKGROUND DATA: Macrophages infiltrate the DRG after
      application of nucleus pulposus (NP) on the DRG, and may play an important role
      in radiculopathy. However, the mechanisms of macrophages infiltration after NP
      application remain poorly understood. METHODS: After experimental disc herniation
      in this study, we investigated changes in the expression of ED1 (a marker of
      macrophages) and vascular cell adhesion molecule-1 (VCAM-1) in DRG using
      immunofluorescence. We also investigated the expression of ED1 and VCAM-1 in DRG
      by treatment with tumor necrosis factor-alpha (TNF-alpha) inhibitor at the time
      of surgery. RESULTS: We found a massive ED1-positive macrophages infiltrated the
      DRG, and VCAM-1-like immunoreactivity vessels became evident after NP
      application. Furthermore, both macrophage infiltration and VCAM-1 expression were
      prevented by treatment with TNF-alpha inhibitor at the time of surgery.
      CONCLUSION: These findings indicated that macrophages infiltration into the DRG
      was TNF-alpha-dependent, and might be partly mediated by VCAM-1 in the early
      stage of experimental lumbar disc herination. Taken together, this study provides
      important preliminary data suggesting that TNF-alpha plays an important role in
      the macrophage infiltration. LEVEL OF EVIDENCE: N/A.

PMID- 23963021
TI  - Early prediction of tumour response to PRRT. The sequential change of tumour
      absorbed doses during treatment with 177Lu-octreotate.
AB  - [177Lu-DOTA0,Tyr3]-octreotate (177Lu-octreotate) in peptide receptor radionuclide
      therapy (PRRT) offers direct intra-therapeutic dosimetry. The aim of this study
      was to compare tumour and non-tumour parameters and assess intra-individual
      variations. PATIENTS, METHODS: Retrospective analysis of 53 consecutive PRRT
      treatment cycles (mean activity of 7.53 +/- 0.46 GBq 177Lu-octreotate, intended
      four cycles at intervals of 10-14 weeks, standard nephroprotection) in 27 GEP NET
      patients. Extended planar dosimetry with serial whole-body imaging on selected,
      non-superimposed tumour and non-tumour regions; liver (LM), bone (BM), and other
      (OM) metastases. The per-cycle variation was compared with post-treatment
      response (CT/MRI three months post-treatment, modified SWOG criteria). RESULTS:
      Residence time in tumor lesions (133-147 h) exceeded that in kidneys (93 h).
      Tumour-to-kidney absorbed dose ratios ranged from 14 to 28 (LM, BM, OM). Intra
      individual per-cycle dose variation was insignificant for kidneys, but
      significant for metastases (LM, BM, and OM; p < 0.05). The mean per-cycle
      decrease of tumour absorbed dose (DeltaD/A0[%]) was linked to morphologic
      response after PRRT. A mean decrease of >20% was predictive of a partial or minor
      remission in all 11 evaluable patients, while absent significant dose reduction
      indicated stable or progressive disease in 4/5 patients. The dose decrease was
      unrelated to volume effects and also observed for BM. CONCLUSION: Besides
      confirmation of a favourable tumour-to-kidney parameter relation for 177Lu
      octreotate, stepwise intra-lesional comparison seems to imply a prognostic impact
      of tumor dosimetry: The early per-cycle change DeltaD/A0 between treatment cycles
      may predict the outcome after PRRT. Larger studies are needed to confirm this
      finding.

PMID- 23963022
TI  - A dual functional MOF as a luminescent sensor for quantitatively detecting the
      concentration of nitrobenzene and temperature.
AB  - We report here a luminescent metal-organic framework [Zn3(TDPAT)(H2O)3] [TDPAT =
      2,4,6-tris(3,5-dicarboxyl phenylamino)-1,3,5-triazine] exhibiting strong
      luminescence at room temperature, which can serve as the first case of a dual
      functional luminescent sensor for quantitatively detecting the concentration of
      nitrobenzene and temperature.

PMID- 23963023
TI  - Deriving the time course of glutamate clearance with a deconvolution analysis of
      astrocytic transporter currents.
AB  - The highest density of glutamate transporters in the brain is found in
      astrocytes. Glutamate transporters couple the movement of glutamate across the
      membrane with the co-transport of 3 Na+ and 1 H+ and the counter-transport of 1
      K+. The stoichiometric current generated by the transport process can be
      monitored with whole-cell patch-clamp recordings from astrocytes. The time course
      of the recorded current is shaped by the time course of the glutamate
      concentration profile to which astrocytes are exposed, the kinetics of glutamate
      transporters, and the passive electrotonic properties of astrocytic membranes.
      Here we describe the experimental and analytical methods that can be used to
      record glutamate transporter currents in astrocytes and isolate the time course
      of glutamate clearance from all other factors that shape the waveform of
      astrocytic transporter currents. The methods described here can be used to
      estimate the lifetime of flash-uncaged and synaptically-released glutamate at
      astrocytic membranes in any region of the central nervous system during health
      and disease.

PMID- 23963024
TI  - Nonlinear pressure dependence of TN in almost multiferroic EuTiO3.
AB  - The antiferromagnetic (AFM) phase transition temperature TN of EuTiO3 has been
      studied as a function of pressure p. The data reveal a nonlinear dependence of TN
      on p with TN increasing with increasing pressure. The exchange interactions
      exhibit an analogous dependence on p as TN (if the absolute value of the nearest
      neighbor interaction is considered) and there is evidence that the AFM transition
      is robust with increasing pressure. The corresponding Weiss temperature ThetaW
      remains anomalous since it always exhibits positive values. The data are analyzed
      within the Bloch power law model and provide excellent agreement with experiment.

PMID- 23963025
TI  - Surgical decision-making process: more questions than answers.

PMID- 23963026
TI  - Surgery, surgeon, and measurement of value and quality of surgeons' work.
AB  - Surgery has undergone a significant change and development entering the 21st
      century. The changes and development have been technology driven, both in therapy
      and diagnosis. There have been significant changes in the health-care systems as
      well universally. The changes have created a significant challenge both for the
      profession and the surgeon. The surgeon should be prepared for further
      developments and innovations and adapt himself or herself to survive practicing
      surgery and conserving the humanistic approach of medicine and professionalism
      including respect to professional values. The profession needs to prepare itself
      for the future to train good surgeons accordingly for better community health.

PMID- 23963027
TI  - Feasibility of radical cytoreductive surgery and hyperthermic intraperitoneal
      chemotherapy for pseudomyxoma peritonei of appendiceal origin.
AB  - BACKGROUND AND AIMS: We analyzed the feasibility of cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma
      peritonei. MATERIAL AND METHODS: A prospective database comprised 90 consecutive
      patients with demonstrable pseudomyxoma peritonei collected during 48 months.
      These patients, referred to our unit for consideration for cytoreductive surgery
      and hyperthermic intraperitoneal chemotherapy, received both cytoreductive
      surgery and hyperthermic intraperitoneal chemotherapy if possible. We evaluated
      the factors associated with a successful procedure. RESULTS: Hyperthermic
      intraperitoneal chemotherapy was successfully delivered to 56 of 90 patients
      (62%) with demonstrable pseudomyxoma peritonei. Tumor morphology of low grade (p
      = 0.013), age under 65 years (p = 0.004), and serum carcinoembryonic antigen
      level under 5.0 ug/L (p = 0.003) were associated with successful administration
      of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Mean
      peritoneal cancer index was lower (18.9 vs 32.6, p < 0.001) and age was younger
      (54.3 vs 61.6, p = 0.003) in patients who underwent hyperthermic intraperitoneal
      chemotherapy than in patients who did not. Four patients had complete
      cytoreductive surgery alone, and 20 patients underwent palliative debulking, but
      10 were ineligible for this operation. CONCLUSIONS: Although the combination of
      cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is currently
      suggested the standard practice for pseudomyxoma peritonei, not all patients are
      eligible for this protocol. In this study, hyperthermic intraperitoneal
      chemotherapy was suitable for 62% of patients with pseudomyxoma peritonei of
      appendiceal origin.

PMID- 23963028
TI  - Outcome of 132 consecutive reconstructive operations for intestinal fistula-
      staged operation without primary anastomosis improved outcome in retrospective
      analysis.
AB  - AIM: To study factors that influenced healing and survival after attempted
      closure of enterocutaneous fistula. MATERIAL AND METHODS: Retrospective analysis
      of prospective data concerning 101 patients operated on 132 instances for 110
      enterocutaneous fistulae at two hospitals. RESULTS: In all, 96 (87%) of the 110
      fistulae healed and 92 (91%) patients survived. A total of 9 patients with
      unhealed fistula died. Multivariate analysis revealed jaundice as an independent
      factor for both death and failed closure and operation without anastomosis as an
      independent positive factor for healing. Failure rate was lower after an
      operation with stoma without anastomosis (6 of 43, 14%) than after an operation
      with anastomosis (30 of 89, 34%) p = 0.0213. Of the 36 instances with unhealed
      fistula, 13 (36%) could be ascribed to inadvertent bowel lesions at the
      reconstructive operation. In addition, univariate analysis revealed that patients
      with previous multiple laparotomies or with multiple operations for
      enterocutaneous fistula healed less likely and had higher mortality. A low serum
      albumin, high white blood cell count, high C-reactive protein concentration, high
      fistula output, total parenteral nutrition, and operation for recurrent fistula
      were associated with death together with long operation time and operative
      bleeding, both indicators of surgical complexity. Over time, staged surgery
      avoiding anastomosis increased from 27% to 57%. Mortality decreased from 12% to
      6%, and healing increased from 73% to 94%. CONCLUSIONS: Chronic inflammation,
      malnutrition, and liver failure causing an impaired healing capacity are
      important reasons for failure. Staged operation without primary anastomosis may
      allow the patient to reverse this condition and improve outcome. The high
      surgical complexity is a negative factor that requires careful planning of the
      operation.

PMID- 23963029
TI  - Declining cholecystectomy rate during the era of statin use in Finland: a
      population-based cohort study between 1995 and 2009.
AB  - BACKGROUND AND AIMS: Aging with comorbidities, obesity, and rapid recovery from
      operation may increase the need for laparoscopic cholecystectomy, but long-term
      use of statins may be associated with a decreased risk of gallstones. This
      population-based cohort study presents the changing rate and causative factors of
      laparoscopic cholecystectomy in Finland during the era of statin use. MATERIALS
      AND METHODS: Age structure of the population, changes in body mass index and
      diabetes, and the number of all cholecystectomies in 1995-2009 were retrieved
      from the registers of National Institute for Health and Welfare. Additionally,
      these results were supplemented by a population-based retrospective cohort (1581
      laparoscopic cholecystectomy) in one community-based hospital area. The risk
      factors for laparoscopic cholecystectomy, use of statins, and surgical outcome
      were analyzed. RESULTS: During the 15 years, 123,794 cholecystectomies were
      performed in Finland, of which 94,740 (76.5%) were performed using laparoscopic
      technique. The median rate of laparoscopic cholecystectomy varied between 110 and
      140 operations per 100,000 inhabitants. In 1995-2009, the annual number of
      cholecystectomies decreased from 8600 to 7500, the number of laparoscopic
      cholecystectomies increased by 10%, and the number of open cholecystectomies
      declined by 60%. In a cohort of 1581 laparoscopic cholecystectomies, the
      proportion of elderly (>65 years of age), obese (body mass index > 30 kg/m(2)),
      and diabetic patients increased from 17% to 28%, 9% to 34%, and 4% to 8%,
      respectively. Use of statins increased more than fourfold during the 15 years.
      CONCLUSIONS: The rates of all cholecystectomies decreased despite marked increase
      in laparoscopic cholecystectomies performed. The increase in risk factors for
      gallstones in Finland implied more marked increase in laparoscopic
      cholecystectomies. The possible role of statins on gallstone disease is
      discussed.

PMID- 23963030
TI  - Effects of intra-arterial octreotide on pancreatic texture: a randomized
      controlled trial.
AB  - BACKGROUND AND AIMS: Octreotide is suggested to harden the pancreas, thus
      facilitating the construction of a pancreatic anastomosis and lowering the risk
      of postoperative fistula. We tested the hypothesis that intra-arterial
      application of octreotide in the gastroduodenal artery during pancreatectomy may
      increase pancreatic hardness. MATERIAL AND METHODS: A single-center, prospective,
      double-blinded, randomized controlled trial with parallel assignment was
      conducted. Patients planned for a pancreatoduodenectomy or a total
      pancreatectomy, who had a palpatory and durometer proven (<40 Shore units) soft
      pancreas, were assigned to receive intraoperatively either 5 mL 500ug octreotide
      or 5 mL 0.9% saline solution as a bolus injection in the gastroduodenal artery.
      Pancreatic hardness was measured before, early, and late after intervention. The
      investigator performing the durometer measurements and pathologist were masked to
      group assignment. The primary outcome was increased pancreatic hardness. Analysis
      was by intention to treat. This trial is registered at
      http://www.clinicaltrials.gov (ID NCT01400100). RESULTS: A total of 12 patients
      received octreotide and 13 received saline solution. Pancreatic hardness
      marginally increased in the octreotide group: 0.67 +/- 2.3 Shore units, whereas
      it decreased in the control group: -2.15 +/- 2.7 Shore units. The difference was
      statistically significant, p = 0.029 (95% confidence interval = -4.87 to -0.77).
      Histology did not find any correlate for this clinically irrelevant hardening
      effect. CONCLUSIONS: A single bolus application of octreotide did not deliver a
      clinically relevant increase in pancreatic hardness. Future studies on the
      hardening effect of octreotide should employ repeated or continuous preoperative
      administration of this drug.

PMID- 23963031
TI  - Complicated liver echinococcosis: 30 years of experience from an endemic area.
AB  - BACKGROUND AND AIMS: Although declining, cystic echinococcosis is still a serious
      public health issue in Greece. This study evaluated the clinical features,
      management, and short-term outcome of patients with complicated liver
      echinococcosis. MATERIAL AND METHODS: A total of 227 patients who were operated
      on for 322 echinococcal cysts of the liver were retrospectively evaluated.
      Patients were divided into those with complicated disease (53.7%) and those with
      noncomplicated disease (46.3%). Intrabiliary rupture (34.4%), cyst infection
      (32.7%), and their combination (24.5%) were the most common complications.
      Demographic characteristics, previous hydatid cyst surgery, cyst multiplicity and
      location, presenting symptoms and signs, types of complicated disease, operative
      procedures performed, postoperative complications, and hospital stay were
      assessed. RESULTS: Patient demographics and cyst characteristics demonstrated no
      significant difference between the two groups. The complicated disease group had
      significantly more pronounced clinical presentations and higher postoperative
      morbidity. Choice of surgical procedure depended upon cyst location and surgeon
      preference. Both conservative and radical procedures were performed, supplemented
      with additional management of the biliary tree when indicated. CONCLUSIONS:
      Complicated liver echinococcosis demonstrates several distinct features that
      differentiate it from the noncomplicated disease. Frequently severe clinical
      manifestations, complexity of surgical management, and the increased
      postoperative complications characterize complicated liver echinococcal disease.

PMID- 23963032
TI  - Preventive strategies for atrial fibrillation after cardiac surgery in Nordic
      countries.
AB  - BACKGROUND AND AIMS: Atrial fibrillation is a common arrhythmia after cardiac
      surgery. It increases morbidity, length of hospital stay, and costs of operative
      treatment. Beta-blockers, sotalol, amiodarone, corticosteroids, and biatrial
      pacing have been shown to be efficient in the prevention of postoperative atrial
      fibrillation. The aim of this study was to find out how widely different
      prophylactic strategies for postoperative atrial fibrillation are used in
      Scandinavian countries. MATERIAL AND METHODS: An online link for a questionnaire
      was emailed to (214) cardiac surgeons in Finland, Sweden, Norway, Denmark, and
      Estonia to assess the use of prophylactic methods for postoperative atrial
      fibrillation. RESULTS: A total of 97 surgeons responded to the survey. Oral beta
      blockers were routinely used for atrial fibrillation prophylaxis by 62% of
      responders. The main reasons for nonuse of beta-blockers were that responders
      were unconvinced of the evidence of benefit or they preferred some alternative
      prophylaxis. Intravenous beta-blockers were used frequently by 6% of responders.
      Amiodarone was used for prophylaxis by 18% of responders. Nonusers were
      unconvinced of its efficacy, were afraid of its complications, or found its use
      too cumbersome. Other prophylactic atrial fibrillation strategies that were used
      are as follows: sotalol by 2%, magnesium by 17%, corticosteroids by 1%, and
      atrial pacing by 11% of respondents. CONCLUSIONS: There is still widely varying
      implementation of strategies for atrial fibrillation prophylaxis among
      Scandinavian cardiac surgeons. Lack of confidence in the efficacy of these
      approaches is the main rationale for nonimplementation.

PMID- 23963033
TI  - Fenestrated and chimney endografts for juxtarenal aneurysms: early and midterm
      results.
AB  - AIM: To assess the early and short-term outcome of fenestrated and chimney
      grafting for juxtarenal aortic aneurysms. MATERIAL AND METHODS: A prospective
      vascular registry of 28 patients who had undergone elective primary endovascular
      repair for abdominal aortic aneurysm between December 2007 and August 2011 with
      infrarenal neck anatomy unacceptable for conventional endovascular repair.
      Fenestrated endografts were designed based on reconstructed computed tomography
      (CT) data by the authors. Off-the-shelf grafts and stents were used for chimney
      cases. Patients were followed up until 31 May 2012. RESULTS: A total of 21 (75%)
      patients were treated with fenestrated endografts, while 7 (25%) received chimney
      grafts. The mean aneurysm diameter was 65 mm (standard deviation = 7 mm) and the
      median neck length 2.5 mm (range: 0-10 mm). Altogether, 63 (mean = 2.3/patient)
      visceral arteries were incorporated (42 renal, 21 superior mesenteric arteries).
      The overall primary technical success rate was 93% (one type I and one type III
      endoleak). The mean follow-up was 22 months (standard deviation: 14 months). The
      primary type III endoleak resolved spontaneously with thrombosis of the target
      vessel, while the patient with primary type I endoleak died of acute myocardial
      infarction 3 weeks after the procedure. Two late endoleaks developed: one type II
      endoleak without aneurysm sac growth remains under surveillance, while in another
      patient, multiple attempts to treat type I endoleak proved unsuccessful and the
      patient later died of gastrointestinal bleeding. A total of 4 (14%) patients so
      far required additional procedures. Two patients died within 30 days of the
      device implantation and another six during the follow-up. No rupture occurred.
      The cumulative survival for patients with fenestrated endografts was 85% at 1
      year and for those treated with chimney technique 57%. CONCLUSIONS: The treatment
      of juxtarenal aortic aneurysms seems to be feasible by exploiting various
      endovascular techniques. Even with a low volume of cases, good immediate and
      short-term results can be achieved, especially with fenestrated endografts.

PMID- 23963034
TI  - Upper cervical spine fusion in children with skeletal dysplasia.
AB  - BACKGROUND: Skeletal dysplasias have been associated with upper cervical
      instability. Many patients are initially asymptomatic, but the instability may
      progress to subluxation and dislocation and complications thereof, including
      death. Surgery is hampered by petite osseous structures and low bone formation
      rate. AIM: To review the outcomes of surgical fusion of upper cervical
      instability in children with rare skeletal dysplasias. MATERIAL AND METHODS: A
      retrospective study of eight children with five different rare skeletal
      dysplasias needing upper cervical instrumented stabilization. Cases were
      evaluated for clinical, radiologic, and quality-of-life outcomes, with median
      follow-up time of 5 years. RESULTS: Six patients underwent posterior, segmental
      cervical spine instrumentation and fusion (three C1/C2 fusions, three
      occipitocervical fusions), one anterior cervical instrumented spinal fusion, and
      one anteroposterior fusion. Autogenous bone grafting was used in all patients,
      and seven were immobilized using a halo body jacket. Nonunion in occipitocervical
      fusions was common in these patients (3/8 patients). Rib autograft from occiput
      to cervical spine with recombinant human BMP-2 was used to salvage nonunions.
      CONCLUSIONS: Surgical fixation in the pediatric cervical spine is hampered by
      fragile posterior structures. A postoperative immobilization by halo vest for 4
      months is customary. Selective anterior corpectomy and plate fixation is not
      recommended in pediatric patients with skeletal dysplasias. LEVEL OF EVIDENCE:
      Level 4, Case Series.

PMID- 23963035
TI  - The effect of different bearing surfaces on metal ion levels in urine following
      28 mm metal-on-metal and 28 mm metal-on-polyethylene total hip arthroplasty.
AB  - BACKGROUND AND AIMS: Recent advancements in manufacturing technology have enabled
      more precise tolerances and surface finishes using metal-on-metal bearing
      surfaces in total hip arthroplasty. The aim of this study was to compare the
      level of metal ions in urine after implantation of a 28-mm metal-on-metal bearing
      manufactured from high-carbon wrought alloy and a 28-mm metal-on-polyethylene
      bearing. MATERIAL AND METHODS: A total of 92 total hip arthroplasty patients were
      prospectively randomized into two groups: those receiving metal-on-metal bearings
      and those receiving metal-on-polyethylene bearings. Chromium, cobalt, and
      molybdenum ion levels in urine were measured preoperatively and at 1 year and 2
      years postoperatively. RESULTS: In the metal-on-polyethylene group, there was a
      slight increase in mean chromium and cobalt concentrations at 2-year follow-up
      compared to the preoperative level (p = 0.02 for both chromium and cobalt). In
      the metal-on-metal group, there was a 15-fold increase in chromium and a 26-fold
      increase in cobalt at 2-year follow-up compared to the preoperative level (p <
      0.001 for both chromium and cobalt). However, the quantity of chromium and cobalt
      in urine from the metal-on-metal group was not higher at 2-year follow-up than at
      1-year follow-up (p = 0.5 and p = 0.6, respectively). CONCLUSIONS: The 28-mm
      metal-on-metal bearings yield chromium and cobalt concentrations in urine that
      can be higher than those recommended for occupational exposure. However, our
      results also indicate that a steady state in wear and ion production using metal
      on-metal total hip arthroplasty can occur.

PMID- 23963036
TI  - Surgery cancelation on the day of surgery in same-day admission in a Finnish
      hospital.
AB  - BACKGROUND AND AIMS: Surgery cancelations cause inappropriate use of hospital
      resources and additional financial and psychological stress to patients.
      Cancelation rates have been described to be even more than 10% of scheduled
      cases. Preoperative anesthesia evaluation clinics have been initialized to
      decrease cancelation rates. At Hyvinkaa hospital, 95% of elective surgical
      patients are admitted on the morning of operation, and only 25% of these patients
      visit preoperative anesthesia evaluation clinic prior to surgery. Cancelation
      rate in Finnish hospitals has not been described. MATERIAL AND METHODS: We
      studied retrospectively 12,205 scheduled elective same-day admission surgical
      cases at Helsinki and Uusimaa Hospital District, Hyvinkaa hospital for a period
      of 2 years. Obstetric cases, emergency cases, and a few inpatient cases were
      excluded. A case was considered as canceled if surgery was canceled after the
      finalization of operation room schedule for the next day. Cancelation rates among
      different specialties and reasons for cancelation were analyzed. RESULTS: A total
      of 12,205 surgeries were scheduled during the study period, and 551 (4.5%) of
      these were canceled. The highest cancelation rate was in hand surgery, with 8.2%
      of scheduled cases, followed by orthopedic surgery with 5.4%, and pediatric
      surgery with 5.1% cancelation rate. Endocrinology had no cancelations, and
      breast, urology, and vein surgery also had less than 2% of canceled cases.
      Patient-related issues caused 72.4% of cancelations, and operation no longer
      being necessary caused 26% of all cancelations. CONCLUSIONS: Day of surgery
      cancelation rate was low in same-day admission, although it varied between
      specialties. Specialties having explicit surgery indications had fewer
      cancelations than specialties having surgery indications based on more subjective
      diagnostic. Process improvements need to be considered continuously to further
      decrease cancelation rate.

PMID- 23963037
TI  - Extraumbilical single-incision laparoscopic cholecystectomy with standard
      laparoscopic instruments.
AB  - BACKGROUND AND AIM: Single-incision laparoscopic surgery is a rapidly progressing
      field as it combines some advantages such as cosmesis and less incisional pain.
      However, it also has some disadvantages such as limitation of movement and
      clashing of the hand instruments, which increase the complexity and technical
      challenges of the operation. In this study, we describe a pilot trial of single
      incision laparoscopic cholecystectomy through a paramedian access site. MATERIAL
      AND METHODS: A total of 25 patients underwent single-incision laparoscopic
      cholecystectomy with this method. Acute cases with empyema and patients with
      history of previous abdominal surgery were excluded. Single-incision is
      established on the right upper quadrant, right latero-superior of the umbilicus,
      so that trocar sites and projection of the gallbladder on the abdominal wall are
      on the same vertical line. Standard laparoscopic instruments were placed into the
      abdominal cavity providing triangulation. Once the laparoscope, grasper, and
      dissector are in place, the overall procedures are similar to the standard
      laparoscopic cholecystectomy. RESULTS: Single-incision laparoscopic
      cholecystectomy through an extraumbilical access site was successfully completed
      in all 25 patients without conversion to open surgery. Additional skin incisions
      and trocar access were required only in two patients. The mean operative time was
      39.3 min (range: 20-75 min). The mean body mass index was 27.2. Postoperative
      course was uneventful in all patients. The mean postoperative hospital stay was
      shorter than 24 h, and all patients were discharged at first day postoperatively.
      No postoperative complications including seroma, wound infection, and trocar-site
      hernia were observed at 6-month follow-up. CONCLUSION: We described a new access
      site for single-incision laparoscopic cholecystectomy using standard laparoscopic
      instruments. We believe that this type of access site overcomes the technical
      difficulties of performing single-incision laparoscopic cholecystectomy, and it
      is a promising alternative method for the treatment of patients with symptomatic
      gallstone disease as a minimal invasive abdominal surgery.

PMID- 23963039
TI  - Partial IFN-gammaR2 deficiency is due to protein misfolding and can be rescued by
      inhibitors of glycosylation.
AB  - We report a molecular study of the two known patients with autosomal recessive,
      partial interferon-gamma receptor (IFN-gammaR)2 deficiency (homozygous for
      mutations R114C and G227R), and three novel, unrelated children, homozygous for
      S124F (P1) and G141R (P2 and P3). IFN-gammaR2 levels on the surface of the three
      latter patients' cells are slightly lower than those on control cells. The
      patients' cells also display impaired, but not abolished, response to IFN-gamma.
      Moreover, the R114C, S124F, G141R and G227R IFNGR2 hypomorphic alleles all encode
      misfolded proteins with abnormal N-glycosylation. The mutants are largely
      retained in the endoplasmic reticulum, although a small proportion reach and
      function at the cell surface. Strikingly, the IFN-gamma response of the patients'
      cells is enhanced by chemical modifiers of N-glycosylation, as previously shown
      for patients with gain-of-glysosylation T168N and misfolding 382-387dup null
      mutations. All four in-frame IFNGR2 hypomorphic mutant alleles encoding surface
      expressed receptors are thus deleterious by a mechanism involving abnormal N
      glycosylation and misfolding of the IFN-gammaR2 protein. The diagnosis of partial
      IFN-gammaR2 deficiency is clinically useful, as affected patients should be
      treated with IFN-gamma, [corrected] unlike patients with complete IFN-gammaR2
      deficiency. Moreover, inhibitors of glycosylation might be beneficial in patients
      with complete or partial IFN-gammaR2 deficiency due to misfolding or gain-of
      glycosylation receptors.

PMID- 23963040
TI  - Interleukin-7 is produced by afferent lymphatic vessels and supports lymphatic
      drainage.
AB  - The cytokine interleukin (IL)-7 exerts essential roles in lymph node (LN)
      organogenesis and lymphocyte development and homeostasis. Recent studies have
      identified lymphatic endothelial cells (LECs) as a major source of IL-7 in LNs.
      Here, we report that LECs not only produce IL-7, but also express the IL-7
      receptor chains IL-7Ralpha and CD132. Stimulation with recombinant IL-7 enhanced
      LEC in vitro activity and induced lymphangiogenesis in the cornea of wild-type
      (WT) mice. Whereas in IL-7Ralpha(-/-) mice, dermal lymphatic vessels (LVs) were
      abnormally organized and lymphatic drainage was compromised, transgenic
      overexpression of IL-7 in mice resulted in an expanded dermal LV network with
      increased drainage function. Moreover, systemic treatment with recombinant IL-7
      enhanced lymphatic drainage in the skin of WT mice and of mice devoid of
      lymphocytes. Experiments in IL-7Ralpha(-/-) bone marrow chimeras demonstrated
      that the drainage-enhancing activity of IL-7 was exclusively dependent on IL
      7Ralpha expression in stromal but not in hematopoietic cells. Finally, near
      infrared in vivo imaging performed in IL-7Ralpha(-/-) mice revealed that the
      pumping activity of collecting vessels was normal but fluid uptake into lymphatic
      capillaries was defective. Overall, our data point toward an unexpected new role
      for IL-7 as a potential autocrine mediator of lymphatic drainage. 

PMID- 23963041
TI  - Preferential splenic CD8(+) T-cell activation in rituximab-nonresponder patients
      with immune thrombocytopenia.
AB  - The pathogenic role of B cells in immune thrombocytopenia (ITP) has justified the
      therapeutic use of anti-CD20 antibodies such as rituximab (RTX). However, 60% of
      ITP patients do not respond to RTX. To decipher the mechanisms implicated in the
      failure of RTX, and because the spleen plays a well-recognized role in ITP
      pathogenesis, 12 spleens from ITP patients who had been nonresponders to RTX
      therapy were compared with 11 spleens from RTX-untreated ITP patients and 9
      controls. We here demonstrate that in RTX-nonresponder ITP patients, preferential
      Th1 and Tc1 T lymphocyte polarizations occur, associated with an increase in
      splenic effector memory CD8(+) T-cell frequency. Moreover, in the RTX-
      nonresponder patient group, the CD8(+) T-cell repertoire displays a restricted
      pattern. In the blood, the phenotype of CD8(+) T cells before and after RTX
      treatment is not modified in responders or nonresponders. Altogether, these
      results demonstrate for the first time an activation of splenic CD8(+) T cells in
      ITP patients who did not respond to RTX and suggest their involvement in platelet
      destruction in these patients. 

PMID- 23963043
TI  - Platelets in tissue repair: control of apoptosis and interactions with
      regenerative cells.
AB  - Besides mediating primary hemostasis and thrombosis, platelets play a critical
      role in tissue repair and regeneration. They regulate fundamental mechanisms
      involved in the healing process including cellular migration, proliferation, and
      angiogenesis. Control of apoptosis/cell survival and interaction with progenitor
      cells, which are clinically relevant but poorly understood aspects of platelets
      in tissue repair, will be highlighted in this review. Gaining deeper insight into
      the less well-characterized molecular mechanisms is necessary to develop new
      therapeutic platelet-based options. 

PMID- 23963044
TI  - Bone marrow transplantation for thalassemia from alternative related donors:
      improved outcomes with a new approach.
AB  - Bone marrow transplantation (BMT) performance can be limited by a lack of ideal
      donors, and the role of alternative donor hematopoietic cell transplantation in
      thalassemia is not well established. Here we used a new treatment protocol (Pc
      26.1) in 16 thalassemia patients to perform BMT using phenotypically HLA
      identical or 1-antigen-mismatched relatives (related donors [RDs]). We compared
      these results with HLA-matched sibling (matched sibling donors [MSDs]) BMT in 66
      patients. The entire RD group and 88% of MSD group had sustained engraftment.
      Rejection incidence was 0% in the RD and 12% (95% confidence interval [95% CI],
      6%-21%) in MSD groups (P = .15), with respective thalassemia-free survival
      probabilities of 94% (95% CI, 63%-99%) and 82% (95% CI, 70%-89%) (P = .24).
      Transplant-related mortality was 6% (95% CI, 1%-26%) in the RD group and 8% (95%
      CI, 3%-16%) in the MSD group (P = .83). The intensified new protocol was not
      associated with increased nonhematologic toxicity. The present data show that the
      Pc 26.1 preparative regimen allows thalassemia patients to safely undergo BMT
      from RDs who are not HLA-matched siblings, with transplant outcomes similar to
      patients with MSD grafts. 

PMID- 23963042
TI  - How I treat CNS lymphomas.
AB  - The pathogenesis of primary and secondary central nervous system (CNS) lymphoma
      poses a unique set of diagnostic, prognostic, and therapeutic challenges. During
      the past 10 years, there has been significant progress in the elucidation of the
      molecular properties of CNS lymphomas and their microenvironment, as well as
      evolution in the development of novel treatment strategies. Although a CNS
      lymphoma diagnosis was once assumed to be uniformly associated with a dismal
      prognosis, it is now reasonable to anticipate long-term survival, and possibly a
      cure, for a significant fraction of CNS lymphoma patients. The pathogenesis of
      CNS lymphomas affects multiple compartments within the neuroaxis, and proper
      treatment of the CNS lymphoma patient requires a multidisciplinary team with
      expertise not only in hematology/oncology but also in neurology, neuroradiology,
      neurosurgery, clinical neuropsychology, ophthalmology, pathology, and radiation
      oncology. Given the evolving principles of management and the evidence for
      improvements in survival, our goal is to provide an overview of current knowledge
      regarding the pathogenesis of CNS lymphomas and to highlight promising strategies
      that we believe to be most effective in establishing diagnosis, staging, and
      therapeutic management. 

PMID- 23963047
TI  - In vivo formation of double-stranded T-DNA molecules by T-strand priming.
AB  - During plant genetic transformation, Agrobacterium transfers a single-stranded
      DNA (T-strand) into the host cell. Increasing evidence suggests that double
      stranded (ds) T-DNA, converted from T-strands, are potent substrates for
      integration. Nevertheless, the molecular mechanism governing T-strand conversion
      to dsT-DNA is unknown. Integrated T-DNA molecules typically exhibit deletions at
      their 3' end as compared with their 5' end. We hypothesize that this may result
      from asymmetric polymerization of T-DNA's ends. Here we show that beta
      glucuronidase (GUS) expression from sense T-strands is more efficient than from
      antisense T-strands, supporting asymmetric conversion. Co-transfection with two
      partially complementary, truncated GUS-encoding T-strands results in GUS
      expression, which suggests functional hybridization of the T-strands via
      complementary annealing and supports the notion that T-strands can anneal with
      primers. Indeed, red fluorescent protein (RFP) expression from mutated T-strand
      can be restored by delivery of synthetic DNA and RNA oligonucleotides with
      partial wild-type RFP sequence, implying the involvement of plant DNA repair
      machinery. 

PMID- 23963048
TI  - Revealing and accelerating slow electron transport in amorphous molybdenum
      sulphide particles for hydrogen evolution reaction.
AB  - Electrochemical impedance spectroscopy is used to identify a slow electron
      transport process in hydrogen evolution catalysed by amorphous molybdenum
      sulphides on glassy carbon. A new chemical synthesis leads to an amorphous
      molybdenum sulfide catalyst with a higher electronic conductivity. 

PMID- 23963046
TI  - Acute cardiac and hemodynamic effects of sildenafil on resistant hypertension.
AB  - PURPOSE: Failure to control blood pressure (BP) despite the use of three or more
      drugs characterizes resistant hypertension (RHTN). Impaired endothelial function
      is associated with this condition and phosphodiesterase-5 inhibitors (PDE5i)
      inhibiting cGMP breakdown-reduce BP in RHTN patients. We hypothesized that acute
      administration of PDE5i could ameliorate hemodynamic, endothelial parameters and
      left ventricular diastolic function (LVDF) in RHTN patients. Also, an exploratory
      analysis was performed to assess the influence of the T-786C endothelial NO
      synthase polymorphism on those responses. METHODS: Subjects (n = 26) underwent a
      6-month clinical screening for RHTN diagnosis. Increasing doses of oral
      sildenafil were given at 30 min intervals (37.5, 50 and 100 mg) while continuous
      non-invasive hemodynamic measures were assessed. LVDF, flow mediated dilation
      (FMD), nitrite and cGMP levels were also determined. RESULTS: Mean arterial
      pressure and total peripheral resistance decreased in all patients (84.17 +/-
      21.04 to 75 +/- 17.21 mmHg; 1149 +/- 459.7 to 1037 +/- 340 dyn.s/cm(-5),
      respectively). Likewise, sildenafil improved diastolic dysfunction parameters
      (Left atrial volume: 25 +/- 5.8 to 20 +/- 4.4; IVRT: 104 +/- 19.33 to 88 +/-
      15.22; E/e' septal: 9.7 +/- 3.8 to 7.9 +/- 2.9; E/e' lateral: 7.7 +/- 3.4 to 6.4
      +/- 3.2). No statistical changes were found in FMD, nitrite and cGMP with PDE5i.
      CONCLUSION: Our data suggest PDE5i acutely improves diastolic function and
      hemodynamic profile in RHTN subjects, despite unchanging endothelial dysfunction.

PMID- 23963049
TI  - Cognitive Strategies, Working Memory, and Growth in Word Problem Solving in
      Children With Math Difficulties.
AB  - This study investigated the role of strategy instruction and working memory
      capacity (WMC) on word problem solving accuracy in children with (n = 100) and
      without (n = 92) math difficulties (MD). Within classrooms, children in Grades 2
      and 3 were randomly assigned to one of four treatment conditions: verbal-only
      strategies (e.g., underlining question sentence), verbal + visual strategies,
      visual-only strategies (e.g., correctly placing numbers in diagrams), or
      untreated control. Strategy interventions included 20 sessions in both Year 1 and
      Year 2. The intent-to-treat as well as the "as-treated" analyses showed that
      treatment effects were significantly moderated by WMC. In general, treatment
      outcomes were higher when WMC was set to a high rather than low level. When set
      to a relatively high WMC level, children with MD performed significantly better
      under visual-only strategy conditions and children without MD performed better
      under verbal + visual conditions when compared to control conditions. 

PMID- 23963050
TI  - Underlying reading-related skills and abilities among adult learners.
AB  - This exploratory study identified underlying skill and ability differences among
      subgroups of adolescent and young adult struggling readers (N = 290) overall and
      in relation to a fluency-based instructional grouping method. We used principal
      axis factoring of participants' scores on 18 measures of reading-related skills
      and abilities identified in the research literature to identify a smaller set of
      generally uncorrelated constructs. The four underlying factors of the 18 measures
      explained 62.7% of the variance. We labeled these factors Encode/Decode (44.5%),
      Vocabulary (9.5%), Processing Speed (5.2%), and Working Memory (3.5%). Regression
      analysis demonstrated Working Memory, Encode/Decode, and Vocabulary collectively
      predicted 45.9% functional reading as measured by the Comprehensive Adult Student
      Assessment System. Alternatively, when measured by the Test of Adult Basic
      Education, Vocabulary and Encode/Decode predicted 47.1% of variance in reading.
      Differences in predictive utility of the factors by fluency group suggest
      approaches to tailoring instruction for each group. Future research might examine
      the optimal mix of instructional approaches that support the identified factors. 

PMID- 23963051
TI  - Skin discolouration with acute onset parkinsonism secondary to systemic zirconium
      intoxication.
AB  - A 72-year-old woman presented with suspected parkinsonism and discolouration of
      the skin especially on sun-exposed areas. Thorough investigation revealed
      systemic zirconium intoxication due to intake of metallic colloids as a home
      remedy as a cause of the skin colour change. There may be an association between
      skin discolouration and her parkinsonism. This is unique in that various clinical
      manifestations developed following systemic ingestion of zirconium and this
      should serve as a warning on the risk of taking illicit dietary supplements. 

PMID- 23963052
TI  - Excretion of N(1), N(12)-diacetylspermine in the urine of healthy individuals.
AB  - BACKGROUND: Urinary N(1),N(12)-diacetylspermine (DiAcSpm) is a novel tumour
      marker that can be used to detect early cancers. In this study, we examined
      whether spot urine samples could represent the daily excretion of DiAcSpm after
      creatinine normalization and which factors should be taken into account in
      determining reference values for this biomarker. METHODS: We collected the
      following urine samples: (1) samples from seven healthy volunteers collected on
      each day of two 2-day sessions to examine the circadian variation of DiAcSpm
      excretion; (2) samples from 3952 male and 1782 female volunteers to estimate the
      DiAcSpm concentrations in apparently healthy adults and (3) samples from 16
      female volunteers collected every morning over a 3-month period to examine the
      menstruation-related variation in DiAcSpm excretion. The DiAcSpm concentrations
      were determined by enzyme-linked immunosorbent assay or a colloidal gold
      aggregation procedure using DiAcSpm-specific antibodies. RESULTS: (1) The
      circadian variation of DiAcSpm in the urine was greatly diminished after
      creatinine normalization. (2) DiAcSpm was higher in females than in males, and
      the creatinine-normalized medians (95th percentile) of the urinary DiAcSpm
      concentrations were 149 (305) and 100 (192) nmol/g creatinine for females and
      males, respectively. (3) The mean concentrations of urinary DiAcSpm were lower
      after menstruation than before menstruation by approximately 30 nmol/g
      creatinine. CONCLUSION: Spot urine samples obtained at any time of a day may be
      used to estimate the daily excretion of DiAcSpm in nmol DiAcSpm per gram
      creatinine. Sex, age and menstrual condition should be considered when
      determining the reference values for urinary DiAcSpm.

PMID- 23963053
TI  - Orientated anatase TiO2 nanocrystal array thin films for self-cleaning coating.
AB  - We developed a simple method to synthesize TiO2 nanowire arrays with nearly 100%
      exposed {001} facets. The coating exhibits good transparency. The thin films of
      TiO2 nanowire arrays display a very good photocatalytic degradation of dye
      molecules and good durability. Based on the above features, the TiO2 nanowire
      array coating is advantageous for self-cleaning coating. 

PMID- 23963054
TI  - Growth hormone response to catecholamine depletion in unmedicated, remitted
      subjects with major depressive disorder and healthy controls.
AB  - We investigated whether the human growth hormone (HGH) response to catecholamine
      depletion differs between fully remitted patients with major depressive disorder
      and healthy control subjects. Fourteen unmedicated subjects with remitted major
      depressive disorder (RMDD) and 11 healthy control subjects underwent
      catecholamine depletion with oral alpha-methylparatyrosine (AMPT) in a
      randomized, placebo-controlled, double-blind crossover study. The main outcome
      measure was the serum level of HGH. The diagnosis * drug interaction for HGH
      serum concentration was significant (F1,23 = 7.66, P < 0.02). This interaction
      was attributable to the HGH level increasing after AMPT administration in the
      RMDD subjects but not in the healthy subjects. In the RMDD sample, the AMPT
      induced increase in HGH concentration correlated inversely with AMPT-induced
      anxiety symptoms as assessed using the Beck Anxiety Inventory (r = -0.63, P <
      0.02). There was a trend toward an inverse correlation of the AMPT-induced HGH
      concentration changes with AMPT-induced depressive symptoms as measured by the
      BDI (r = -0.53, P = 0.05). Following catecholamine depletion, the RMDD subjects
      were differentiated from control subjects by their HGH responses. This finding,
      together with the negative correlation between HGH response and AMPT-induced
      anxiety symptoms in RMDD subjects, suggests that AMPT administration results in a
      deeper nadir in central catecholaminergic transmission, as reflected by a greater
      disinhibition of HGH secretion, in RMDD subjects versus control subjects.

PMID- 23963055
TI  - Escalating doses of transdermal nicotine in heavy smokers: effects on smoking
      behavior and craving.
AB  - Fixed-dose nicotine replacement therapy (NRT) is efficacious for smoking
      cessation in the general population of smokers. However, it is less effective in
      populations with psychiatric comorbidities and/or severe tobacco dependence where
      the percent nicotine replacement is suboptimal. The objective of this pilot study
      was to determine the effectiveness of nicotine patch dose titration in response
      to continued smoking in heavily dependent smokers with psychiatric comorbidity.
      In a single-arm, open-label study adult smokers (mean cigarettes per day, 25.4 +/
      13.4; range, 14-43; n = 12) willing to quit were treated with escalating doses
      of transdermal nicotine and brief counseling intervention if they continued to
      smoke over a 9-week treatment period. Plasma nicotine and cotinine, along with
      expired carbon monoxide levels, and the subjective effects of smoking, urge to
      smoke, demand elasticity, and mood symptoms were also assessed. The mean NRT dose
      was 32.7 (SD, 16.4) mg/d (range, 7-56 mg/d). Smokers reported significant
      reductions in both cigarettes per day (mean decrease, 18.4 +/- 11.5) confirmed by
      expired carbon monoxide (mean decrease, 13.5 +/- 13.0) with no significant
      changes in plasma nicotine concentrations during the course of NRT dose
      titration. There were significant effects on the subjective effects of smoking
      and measures of smoking behavior. Most commonly reported adverse events were
      respiratory infections, skin irritation at patch site, nausea, and sleep
      disturbances, which were generally mild and transient. Titrating doses of NRT to
      effect with brief intervention hold promise as an effective clinical strategy to
      assist heavily dependent psychiatrically ill smokers to change their smoking
      behavior. 

PMID- 23963056
TI  - The association study of polymorphisms in DAT, DRD2, and COMT genes and acute
      extrapyramidal adverse effects in male schizophrenic patients treated with
      haloperidol.
AB  - Extrapyramidal symptoms (EPSs) are common adverse effects of antipsychotics. The
      development of acute EPSs could depend on the activity of dopaminergic system and
      its gene variants. The aim of this study was to determine the association between
      dopaminergic type 2 receptor (DRD2) dopamine transporter (SLC6A3) and catechol-O
      methyltransferase (COMT) gene polymorphisms and acute EPSs in 240 male
      schizophrenic patients treated with haloperidol (15-mg/d) over a period of 2
      weeks. Acute EPSs were assessed with Simpson-Angus Scale. Three dopaminergic gene
      polymorphisms, the DRD2 Taq1A, the SLC6A3 VNTR, and the COMT Val158Met, were
      determined. Extrapyramidal symptoms occurred in 116 (48.3%) of patients.
      Statistically significant associations were found for SLC6A3 VNTR and COMT
      Val158Met polymorphisms and EPS susceptibility. Patients with SLC6A3 9/10
      genotype had almost twice the odds to develop EPSs compared with those with all
      other SLC6A3 genotypes (odds ratio, 1.9; 95% confidence interval, 1.13-3.30), and
      patients with COMT Val/Met genotype had 1.7 times greater odds to develop EPSs
      than those with all other COMT genotypes (odds ratio, 1.7; 95% confidence
      interval, 1.01-2.88). There was no statistically significant association between
      genotype and allele frequencies of DRD2, SLC6A3, or COMT polymorphisms and the
      development of particular EPSs.In conclusion, the results of the present study
      showed for the first time the association between acute haloperidol-induced EPSs
      and SLC6A3 VNTR and COMT Val158Met polymorphisms. Although the precise biological
      mechanisms underlying these findings are not yet understood, the results suggest
      that the dopaminergic gene variations could predict the vulnerability to the
      development of the acute EPSs in haloperidol-treated schizophrenic patients.

PMID- 23963057
TI  - Long-term quality-of-life and functioning comparison of atomoxetine versus other
      standard treatment in pediatric attention-deficit/hyperactivity disorder.
AB  - Psychopharmacological agents were shown to be important for improving the quality
      of life (QoL) of patients with attention-deficit/hyperactivity disorder (ADHD). A
      short-term, 10-week study found atomoxetine (ATX) to be effective in improving
      QoL of ADHD patients. We compared, for the first time, long-term treatment
      outcomes of ATX and other early standard therapy (OEST, any pharmacological ADHD
      treatment except ATX) in QoL and functional impairment in pharmacologically naive
      children/ adolescents in a randomized, controlled, open-label study at 6 and 12
      months. Patients received ATX (0.5-1.8 mg/kg per day) or OEST (mainly
      methylphenidate). Quality of life and functioning were assessed by the Child
      Health and Illness Profile-Child Edition, Parent Rating Form and the Weiss
      Functional Impairment Rating Scale-Parent Report. Three hundred ninety-eight
      patients (79.4% male; mean age, 9.3 years) received study treatment. The Child
      Health and Illness Profile-Child Edition, Parent Rating Form achievement domain t
      scores significantly improved from baseline to 6 months from means of 28.0 to
      37.1 for ATX and from 28.3 to 40.7 for OEST. Mean t scores at 12 months were 40.0
      for ATX and 41.0 for OEST. The Weiss Functional Impairment Rating Scale-Parent
      Report total score improved from baseline to 6 months in both groups (ATX: mean
      1.02 to 0.63; OEST: 0.96 to 0.59). Both treatments were safe with no
      statistically significant difference in the overall rate of adverse events.
      Overall, the improvements in QoL and functional impairment observed over time for
      ATX and OEST were meaningful and stable over the study period of 12 months.
      Between-group differences were small but sometimes statistically significant,
      providing the first-time long-term comparative symptomatic and QoL analysis
      between ATX and OEST. 

PMID- 23963058
TI  - A pilot study to compare fluoxetine, calcium, and placebo in the treatment of
      premenstrual syndrome.
AB  - Serotonin reuptake inhibitors and calcium supplements ameliorate symptoms of
      premenstrual syndrome. A comparison of these agents to placebo may guide
      treatment selection. The goal of this pilot study was to compare fluoxetine and
      calcium to placebo.We enrolled 39 women with at least 3 moderate to severe
      premenstrual symptoms and functional impairment. The trial compared fluoxetine
      (10 mg twice daily), calcium carbonate (600 mg twice daily), and placebo over the
      course of 4 menstrual cycles. The Inventory of Depressive Symptomatology,
      Premenstrual Tension Scale, Clinical Global Impression-Severity and -Improvement
      scales, and Daily Record of Severity of Problems were used to measure
      symptoms.Symptom improvement was greatest for the fluoxetine group, although
      significance was achieved only for the Daily Record of Severity of Problems (beta
      = -0.28; 95% confidence interval, -1.70 to -0.35; P = 0.02) and the Clinical
      Global Impression-Improvement (beta = -1.03; 95% confidence interval= -1.70 to 
      0.35; P = 0.04). The Cohen d effect sizes for fluoxetine relative to placebo were
      between 0.80 and 2.08, whereas the effect sizes for calcium were only between
      0.10 and 0.44.Fluoxetine had clear therapeutic benefit for premenstrual syndrome,
      whereas the effect of calcium was much smaller. Results of this pilot do not
      support the need for a larger study that would compare these compounds. 

PMID- 23963059
TI  - Monotherapy with lithium or valproate or respectively combination therapy with
      quetiapine have similar effect on cognitive functions in Chinese euthymic
      patients with bipolar disorder: a cross-sectional survey.

PMID- 23963060
TI  - A feasibility study of varenicline for smoking cessation in bipolar patients with
      subsyndromal depression.

PMID- 23963061
TI  - Treatment of clozapine-induced constipation with bethanechol.

PMID- 23963062
TI  - Bupropion-related visual hallucinations in a veteran with posttraumatic stress
      disorder and multiple sclerosis.

PMID- 23963063
TI  - Zinc hydroxide sulphate and its transformation to crystalline zinc oxide.
AB  - The thermal transformation of zinc hydroxide sulphate hydrate to zinc oxide has
      been examined using synchrotron X-ray diffraction, thermogravimetric analysis,
      scanning electron microscopy, and surface area measurements. By collecting X-ray
      diffraction data in situ, we found that the dehydration of zinc hydroxide
      sulphate pentahydrate proceeded in discrete steps to form anhydrous zinc
      hydroxide sulphate. This compound then decomposed to a mixture of zinc oxide and
      a compound tentatively identified as Zn3(OH)2(SO4)2 at ~235  degrees C. At ~360 
      degrees C, the final dehydroxylation occurred with the formation of zinc oxy
      sulphate, Zn3O(SO4)2, which then decomposed to ZnO at about ~800  degrees C.
      Interruption of the dehydration process can be used to synthesize the
      intermediate compounds.

PMID- 23963064
TI  - Contrasting Cu, Fe, and Zn isotopic patterns in organs and body fluids of mice
      and sheep, with emphasis on cellular fractionation.
AB  - We report Cu, Fe, and Zn natural isotope compositions in organs, body fluids,
      diets and feces of mice and sheep. Large and systematic isotope variability is
      observed, notably in the delta(66)Zn in liver and delta(65)Cu in kidneys, but
      significant differences exist between mice, sheep and humans, especially in the
      delta(66)Zn value of blood. The results are interpreted with reference to current
      knowledge of metal trafficking and redox conditions in cells. In general, the
      light isotopes preferentially fractionate into 'softer' bonds involving sulfur
      such as cysteine and glutathione, whereas heavy isotopes fractionate into
      'harder' bonds involving nitrogen (histidine) and even more oxygen, notably
      hydroxides, phosphates, and carbonates. Bonds involving the reduced forms Cu(+)
      and Fe(2+) are enriched in the light isotopes relative to bonds involving the
      oxidized Cu(2+) and Fe(3+) forms. Differences in blood Zn isotope abundances
      between mice, sheep and humans may reflect a different prevalence of Zn ZIP
      transporters. The isotopically heavy Cu in the kidneys may reflect isotope
      fractionation during redox processes and may be relevant to ascorbate degradation
      into oxalate. 

PMID- 23963065
TI  - A sensitive and specific quantitation method for determination of serum cardiac
      myosin binding protein-C by electrochemiluminescence immunoassay.
AB  - Biomarkers are becoming increasingly more important in clinical decision-making,
      as well as basic science. Diagnosing myocardial infarction (MI) is largely driven
      by detecting cardiac-specific proteins in patients' serum or plasma as an
      indicator of myocardial injury. Having recently shown that cardiac myosin binding
      protein-C (cMyBP-C) is detectable in the serum after MI, we have proposed it as a
      potential biomarker for MI. Biomarkers are typically detected by traditional
      sandwich enzyme-linked immunosorbent assays. However, this technique requires a
      large sample volume, has a small dynamic range, and can measure only one protein
      at a time. Here we show a multiplex immunoassay in which three cardiac proteins
      can be measured simultaneously with high sensitivity. Measuring cMyBP-C in
      uniplex or together with creatine kinase MB and cardiac troponin I showed
      comparable sensitivity. This technique uses the Meso Scale Discovery (MSD) method
      of multiplexing in a 96-well plate combined with electrochemiluminescence for
      detection. While only small sample volumes are required, high sensitivity and a
      large dynamic range are achieved. Using this technique, we measured cMyBP-C,
      creatine kinase MB, and cardiac troponin I levels in serum samples from 16
      subjects with MI and compared the results with 16 control subjects. We were able
      to detect all three markers in these samples and found all three biomarkers to be
      increased after MI. This technique is, therefore, suitable for the sensitive
      detection of cardiac biomarkers in serum samples.

PMID- 23963066
TI  - Activation of cannabinoid CB1 receptors modulates evoked action potentials in rat
      retinal ganglion cells.
AB  - Activation of cannabinoid CB1 receptors (CB1Rs) regulates a variety of
      physiological functions in the vertebrate retina through modulating various types
      of ion channels. The aim of the present study was to investigate the effects of
      this receptor on cell excitability of rat retinal ganglion cells (RGCs) in
      retinal slices using whole-cell patch-clamp techniques. The results showed that
      under current-clamped condition perfusing WIN55212-2 (WIN, 5 MUmol/L), a CB1R
      agonist, did not significantly change the spontaneous firing frequency and
      resting membrane potential of RGCs. In the presence of cocktail synaptic
      blockers, including excitatory postsynaptic receptor blockers CNQX and D-APV, and
      inhibitory receptor blockers bicuculline and strychnine, perfusion of WIN (5
      MUmol/L) hardly changed the frequencies of evoked action potentials by a series
      of positive current injection (from +10 to +100 pA). Phase-plane plot analysis
      showed that both average threshold voltage for triggering action potential and
      delay time to reach threshold voltage were not affected by WIN. However, WIN
      significantly decreased +dV/dtmax and -dV/dtmax of action potentials, suggestive
      of reduced rising and descending velocities of action potentials. The effects of
      WIN were reversed by co-application of SR141716, a CB1R selective antagonist.
      Moreover, WIN did not influence resting membrane potential of RGCs with synaptic
      inputs being blocked. These results suggest that activation of CB1Rs may regulate
      intrinsic excitability of rat RGCs through modulating evoked action potentials. 

PMID- 23963067
TI  - [Role of uteroglobin-binding protein in antiflammin-1 promoting IL-10 expression
      and secretion in RAW264.7 cells induced by endotoxin].
AB  - The present study investigated the effect of antiflammin-1 (AF-1) on LPS-induced
      IL-10 secretion from RAW264.7 cells through uteroglobin-binding protein (UGBP).
      Cultured RAW264.7 cells, a murine monocyte-macrophage cell line, were divided as
      following: control group, LPS group (1 ug/mL LPS), AF-1 group (100 MUmol/L AF-1),
      LPS+AF-1 group (2 h of 100 MUmol/L AF-1 pretreatment before LPS addition), and
      LPS+AF-1+anti-UGBP group (30 min of anti-UGBP antibody pretreatment before
      successive treatments with AF-1 and LPS). IL-10 concentration in the supernatants
      was detected by ELISA assay, and the level of IL-10 mRNA expression in macrophage
      was detected by using RT-PCR method. The results showed that AF-1 significantly
      increased LPS-induced IL-10 secretion in RAW264.7 cells in a dose dependent way,
      and up-regulated its mRNA level. Anti-UGBP antibody pretreatment attenuated the
      augmented effect of AF-1 on LPS-induced IL-10 secretion and gene expression.
      These results suggest that AF-1 promotes LPS-induced IL-10 secretion from
      macrophages, and this effect is mediated by UGBP. 

PMID- 23963068
TI  - Inhibition of peripheral NPY Y1 and Y2 receptors ameliorates the aberrant
      baroreceptor reflex sensitivity in streptozotocin induced diabetic rats.
AB  - Neuropeptide Y (NPY), a sympathetic neurotransmitter, is highly associated with
      baroreflex dysfunction and multiple cardiac diseases such as diabetic
      myocardiopathy. In the present study, we aimed to explore the role of peripheral
      NPY Y1 receptor (Y1R) and Y2 receptor (Y2R), which are dominantly present in
      peripheral cardiovascular control, in baroreflex sensitivity (BRS) of
      streptozotocin (STZ)-induced diabetic rats. Peripheral Y1R and Y2R were
      antagonized by specific antagonists (BIBP 3226 and BIIE 0246, respectively) from
      subcutaneously implanted ALZET mini-osmotic pump in STZ-induced diabetic rats for
      4 weeks. Then baseline systolic blood pressure, heart rate, cardiac function,
      BRS, plasma NPY and lipid levels were evaluated. We found that STZ led to
      increased plasma NPY and lipid level. And the STZ-increased lipid levels were
      reduced by BIBP 3226 and BIIE 0246. BIBP 3226 ameliorated the aberrant BRS, but
      had little effect on the impaired cardiac function of the STZ rats. BIIE 0246
      alleviated sodium nitroprusside (SNP)-induced but not phenylephrine (PE)-induced
      aberrant baroreflex control of heart rate in the STZ rats. In addition, BIIE 0246
      alleviated the bradycardia, but further impaired cardiac contractility in the STZ
      rats. These results suggest that peripheral Y1R and Y2R play different roles in
      STZ-induced impairment of BRS. 

PMID- 23963069
TI  - [Relationship between ER-alpha36 and Akt in PC12 cells exposed to glucose
      deprivation].
AB  - ER-alpha36 is a novel 36-kDa variant of ER-alpha. A large of evidence
      demonstrated that ER-alpha36 responded to membrane-initiated estrogen signaling
      pathways which were involved in the physiological and pathological process in
      many kinds of cells. In this study, knock-down of ER-alpha36 expression in
      pheochromocytoma (PC12) cells (named as PC12-36L cells) by using the shRNA method
      was used to evaluate the relationship between ER-alpha36 and Akt in neurons under
      glucose deprivation. The effect of ER-alpha36 on outgrowth of PC12 cells, as well
      as the neuroprotective effect of ER-alpha36 on injured PC12 cells exposed to
      glucose deprivation was observed by using MTT assay, Western blot and Annexin
      V/PI staining et al. The results showed that, (1) Glucose deprivation induced by
      MEM treatment for 6 h reduced survival rate and increased apoptotic rate in PC12
      cells significantly compared to control group (P < 0.01); and it produced a
      decrease in the expression of Glut-4 protein (P < 0.01); (2) The expression level
      of ER-alpha36 was decreased significantly at 3 h of glucose deprivation, and then
      increased, while phosphorylation of Akt participated in the glucose deprivation
      was increased at first and then reduced; LY294002 (PI3K inhibitor) contributed to
      decreased expression of ER-alpha36, and suppressed the activation of Akt; (3) The
      rate of apoptosis was significantly increased in PC12-36L cells after glucose
      deprivation compared with that in wild type PC12 cells (P < 0.01). Furthermore,
      phosphorylation of Akt was decreased and Caspase-3 was increased by glucose
      deprivation in PC12-36L cells compared with those in wild type PC12 cells. The
      study reveals that phosphorylation of Akt is associated with ER-alpha36 in PC12
      cells exposed to glucose deprivation, and both are involved in the regulation of
      stress responses.

PMID- 23963070
TI  - [Effect of kinetin on ovary and uterus in D-galactose-induced female mouse model
      of aging].
AB  - The present study was to investigate the effect of kinetin on ovary and uterus of
      D-galactose-induced female mouse model of aging. Aging female mice model caused
      by D-galactose were used as model group, the aging model mice intragastrically
      administered with kinetin solution (daily 25 mg/kg or 50 mg/kg) were used as
      kinetin groups, and the mice with solvent as normal group (n = 20). To detect the
      effects of kinetin, estrous cycle, estradiol content, ovarian and uterine wet
      weight and organ index, SOD and GSH-Px activities, MDA and total protein
      contents, as well as the reserve function of ovaries were examined. The results
      showed that, kinetin-induced changes in two kinetin groups were observed,
      compared with the model group: (1) the estrous cycle was shortened; (2) serum
      estradiol content was significantly increased; (3) the wet weights of the ovary
      and uterus were increased significantly; (4) SOD and GSH-Px activities of ovary
      and uterus were significantly higher; (5) the MDA contents of the ovary and
      uterus were reduced significantly; (6) total protein contents of the ovary and
      uterus were increased significantly; (7) the numbers of mature oocytes in
      fallopian tubes were increased significantly. The results show that kinetin can
      protect ovary and uterus against oxidative damage, prevent low estrogen secretion
      caused by ovarian oxidative damage, shorten the estrous cycle in mice, and
      eventually maintain ovarian and uterine vitalities. 

PMID- 23963071
TI  - [Circadian clock gene Rev-erb-alpha deficiency prolongs female estrous
      cyclicity].
AB  - The circadian clock has been linked to female reproductive physiology and
      endocrine in mammals. Epidemiological studies of female shift workers have shown
      increased rates of abnormal reproduction and adverse pregnancy. But little is
      known how the circadian rhythms affect reproduction. The aim of the present study
      was to investigate the influences of circadian rhythms on estrous cycle in female
      mice using clock gene Rev-erb-alpha knock out (Rev-erb-alpha(-/-)) mice. To test
      the fertility of Rev-erb-alpha(-/-) mice, litter sizes were counted after mating
      with C57BL/6J male mice. HE staining was used to observe the change of follicle
      development. The number of embryos of Rev-erb-alpha(+/+) and Rev-erb-alpha(-/-)
      female mice was compared 1.5 d after mating with C57BL/6J male mice. Then Rev-erb
      alpha(+/+) and Rev-erb-alpha(-/-) female mice were housed to adult, and daily
      vaginal lavage with 0.9% saline was used to monitor estrous cycle for at least 30
      days. Quantity of various cells was counted on specified smears views after
      staining. We observed estrous cycles of Rev-erb-alpha(+/+) and Rev-erb-alpha(-/-)
      female mice using line plots and periodic spectrograms. The results showed that
      the Rev-erb-alpha(-/-) female mice were infertility, and the number of embryos of
      Rev-erb-alpha(-/-) females was less than that of Rev-erb-alpha(+/+) females.
      However, the follicle development of Rev-erb-alpha(-/-) female mice was normal.
      The estrous cycle of Rev-erb-alpha(-/-) female mice was 3.22 days longer than
      that of Rev-erb-alpha(+/+) female mice. The results suggest that loss of Rev-erb
      alpha prolongs estrous cycle, which is probably one of the reasons for female
      mice infertility, and circadian rhythm is important for mammalian estrous cycle. 

PMID- 23963072
TI  - [Changes of angiotensin converting enzyme 2 in the occurrence and development of
      diabetic renal injury in rat].
AB  - This project was designed to investigate the role of angiotensin converting
      enzyme 2 (ACE2) in the diabetic renal injury by observing the expression of ACE2
      in the kidney and the level of angiotensin II (AngII) in the circulatory system
      and kidney tissue of rats with diabetes. SD rats were randomly divided into
      control group and diabetes group. Diabetic nephropathy model was established by
      i.p. injection of streptozotocin (STZ). The rats were sacrificed separately on
      the 15th or 30th day after STZ injection. Biochemical parameters including blood
      glucose and renal function were examined. The expression of ACE2 in the kidney
      was detected by real-time PCR and Western blot. The contents of AngII in plasma
      and kidney were detected by radioimmunoassay. The results are as follows: (1) 48
      72 h after STZ injection, the rats showed polyuria, polydipsia and their activity
      reduced. (2) Blood glucose levels were 4.9-6.5 mmol/L in the control rats, 14.0
      17.5 mmol/L in the diabetes group rats on the 15th day, and higher than 24 mmol/L
      in the diabetes group rats on the 30th day; (3) There was a significant increase
      of urine glucose level (P < 0.05), and a slight but not significant increase of
      urine protein level (P > 0.05) in the diabetes group on the 15th day; On the 30th
      day, the levels of urine glucose and urine protein were significantly higher than
      those in the control group (P < 0.01); (4) Compared with the control group, the
      expression of ACE2 mRNA was slightly increased (P > 0.05), and the expression of
      ACE2 protein was significantly increased (P < 0.05) in the rats of diabetic model
      group on the 15th day; however, on the 30th day, ACE2 mRNA expression in the rats
      of diabetic model group was significantly lower than the control group (P <
      0.05), and the expression of ACE2 protein was slightly lower than the control
      group (P = 0.0718). (5) Compared with the control group, the levels of AngII in
      plasma and kidney of the diabetic rats increased slightly on the 15th day (P >
      0.05); while the AngII levels in diabetic model group rats were significantly
      higher (P < 0.05) than that in control rats on the 30th day. These results
      suggest that ACE2 plays a positive role in the protection against the
      pathogenesis of early renal damage. ACE2 expression is reduced gradually with the
      deepened degree of diabetic kidney damage, leading to the accumulation of AngII
      in the kidney, thereby increasing the renal injury. 

PMID- 23963073
TI  - [Effects of extracellular matrix on biological characteristics of late
      endothelial progenitor cells].
AB  - The present study was designed to investigate the effects of various
      extracellular matrix (ECM) proteins on the biological characteristics of late
      endothelial progenitor cells (EPCs). Density gradient centrifugation-isolated rat
      bone marrow mononuclear cells were cultured in complete M199 medium, which
      contained 15% fetal calf serum, 10 MUg/L vascular endothelial growth factor
      (VEGF) and 5 MUg/L basic fibroblast growth factor (bFGF). EPCs were plated on
      substrates containing fibronectin (Fn), laminin (Ln) or rat tail tendon collagen
      (Col), and the corresponding cells were defined as Fn, Ln and Col groups. The 3rd
      generation EPCs, namely late EPCs, were harvested. The proliferation, adhesion,
      migration and the ability of forming tubes were assayed using CCK-8, adhesion
      test, wound healing assay and Matrigel, respectively. The mRNA expressions of
      endothelial cell differentiation markers, vWF and CD31, were analyzed by real
      time RT-PCR. The apoptosis was assayed by flow cytometry (FCM). The results
      showed that cell proliferation ability of Fn and Col groups were higher than that
      of Ln group; Fn group showed increased adhesion compared to Col and Ln groups (P
      < 0.01); The migration ability of Fn and Col groups were higher than that of Ln
      group. Moreover, Fn group showed increased tube formation abilities compared to
      Col and Ln groups (P < 0.05). Although 24-hour free-serum-induced apoptosis in Ln
      group was the highest, there was no difference of auto-apoptosis among the three
      groups. Furthermore, the mRNA expressions of vWF and CD31 exhibited no difference
      among the three groups. These results suggest the ECM affects the biological
      functions of late EPCs, which would have a high probability of providing new
      directions that lead to the development of artificial heart and blood vessels. 

PMID- 23963074
TI  - An engineered multidomain fungicidal peptide against plant fungal pathogens.
AB  - Fungal pathogens represent major problems for human health and agriculture. As
      eukaryotic organisms, fungi share some important features with mammalian cells.
      Therefore, current anti-fungal antibiotics often can not distinguish between
      fungi and mammalian cells, resulting in serious side effects in mammalian cells.
      Accordingly, there is strong impetus to develop antifungal alternatives that are
      both safe and effective. The E1 family of colicin are channel-forming
      bacteriocins produced by Escherichia coli, which are bactericidal only to E. coli
      and related species. To target the channel-forming domain of colicin to fungal
      cell membrane, we engineered a sexual mating pheromone of Candida albicans, alpha
      factor pheromone to colicin Ia. A peptide was constructed consisting of an alpha
      mating pheromone of C. albicans fused to the channel-forming domain of colicin Ia
      to create a new fusion protein, pheromonicin-CA (PMC-CA). Indirect immunolabeling
      showed that the PMC-CA bound to fungal cells and inhibited growth in the
      laboratory and field. In the field, the protective activity of pheromonicin
      against rice blast disease was significantly greater, on a molar basis, than that
      of triazoles, tricyclazole or isoprothiolane. These results suggest that fusion
      peptides may be of value as fungicidal agents under agricultural conditions. 

PMID- 23963075
TI  - Soluble factors from bone marrow endothelial cells regulate differentiation and
      proliferation of hematopoietic and endothelial lineages and embryonic stem cells.
AB  - We have established a bone marrow endothelial cell line. This review focuses on
      the elucidation and analysis of the effects of this bone marrow endothelial cell
      conditioned medium (BMEC-CM) on the differentiation and proliferation of
      hematopoietic and endothelial progenitors as well as embryonic stem cells (ESCs).
      We will review that (1) BMEC-CM promotes proliferation and differentiation of
      hematopoietic lineage; (2) BMEC-CM promotes proliferation and differentiation of
      endothelial lineage; (3) BMEC-CM induces differentiation of hematopoietic stem
      cells/progenitors into endothelial progenitors; and (4) BMEC-CM induces
      differentiation of ESCs into hematopoietic cells and endothelial cells. We
      conclude that the soluble factors secreted by BMECs are able to support the
      proliferation and differentiation of hematopoietic and endothelium lineages.
      Moreover, these soluble factors induce hematopoietic cells to differentiate to
      endothelial cells, and induce ESCs to differentiate towards both endothelial
      cells and hematopoietic cells. Therefore, this work provides evidence that a
      close relationship involved in the development of hematopoietic and endothelial
      lineage. This disclosure will be beneficial for therapy strategy in the treatment
      of ischemic and tumor diseases, and improve our understanding of the relationship
      between hematopoietic and endothelial lineages. 

PMID- 23963076
TI  - [Biological function of Nogo-B].
AB  - Nogo-B is a major family member of the reticulon protein family 4. It is widely
      expressed in the central nervous system and peripheral tissues, and is mainly
      located in endoplasmic reticulum and cell membrane. Previous studies have
      revealed that Nogo-B plays a key role in vascular injury, tissue repair and
      inflammation process. It also may be critical for apoptosis of tumor cells and
      central diseases. Further investigation of the molecular characteristics and
      biological function of Nogo-B might be of great help to understand its role in
      diverse diseases. 

PMID- 23963077
TI  - Role of endogenous cannabinoid system in the gut.
AB  - The plant Cannabis has been used in clinic for centuries, and has been known to
      be beneficial in a variety of gastrointestinal diseases, such as emesis,
      diarrhea, inflammatory bowel disease and intestinal pain. In this text, we'll
      review the components of the endogenous cannabinoid system as well as its role in
      the regulation of gastrointestinal activities, thus providing relative
      information for further study. Moreover, modulation of the endogenous cannabinoid
      system in gastrointestinal tract may provide a useful therapeutic target for
      gastrointestinal disorders. 

PMID- 23963078
TI  - [Method of isolation of intrafusal fibres of muscle spindle in soleus of rats].
AB  - Capsule restricts the further study on muscle spindle function and the involved
      mechanism. The aim of this study was to establish the isolation method of
      intrafusal fibres from the isolated rat muscle spindle. Intrafusal fibres were
      harvested from muscle spindle of soleus muscle in rats using neutrase-collagenase
      digestion. A variety of incubation mediums have been tested to find out an
      appropriate medium of intrafusal fibers in vitro. Trypan blue staining was used
      to detect cell death, and patch clamp was used to record resting potential. The
      results showed that the intrafusal fibres incubated with amine acid-saline
      solution were almost all dead. DMEM could maintain good condition of the fibres,
      but excess CO2 ventilation would induce cellular swelling or even death. While
      Leiboviz's 15 (L-15) medium can guarantee 1-2 h of physiological condition of the
      intrafusal fibres. Coverslips treated with gelatin, polylysine and serum was the
      better interfaces for the intrafusal fibres to adhere easily, compared with
      regularly treated coverslip. The resting potential of intrafusal fibres was (
      45.3 +/- 5.1) mV, consistent with others obtained from in vivo muscle spindle
      from cats and frogs. These results suggest that the isolation method of the
      intrafusal fibres has been successfully established in the present study,
      providing a new approach in better understanding of muscle spindle activities and
      the involved mechanism. 

PMID- 23963079
TI  - Druggable drivers of lung cancer.

PMID- 23963080
TI  - Analysis of electronic structure and its effect on magnetic properties in (001)
      and (110) oriented La0.7Sr0.3MnO3 thin films.
AB  - Epitaxial thin films of half-metallic oxide La0.7Sr0.3MnO3 (LSMO) have been grown
      in two crystalline orientations, one with the c-axis out-of-plane, the (001)
      orientation, and one with the c-axis in-plane, the (110) orientation. For the
      (110) oriented growth, there is no polar discontinuity at the substrate-film
      interface and hence no dead layer formation, which improves ferromagnetic
      interaction in the LSMO, making it highly attractive for spintronic applications.
      In our experiments, with x-ray diffraction, x-ray photoelectron spectroscopy and
      magnetic measurements, we have demonstrated that in the (110) oriented LSMO the
      lattice is more relaxed, leading to less deformation of electronic density around
      the La atom or in the MnO6 octahedra. This improved crystal and electronic
      structure improves the ferromagnetic properties of the films, making the Curie
      temperature higher by almost 15 K, which is of potential interest for
      spintronics. However, substrate strain induced magnetic anisotropy causes domain
      formation with out-of-plane components in these films, which poses some concern
      for practical spintronic devices. 

PMID- 23963082
TI  - Supramolecular dimerisation of middle-chain Phe pentapeptides via CB[8] host
      guest homoternary complex formation.
AB  - Pentapeptides containing a Phe residue in the middle of the sequence exhibit
      ternary complex formation in the presence of cucurbit[8]uril, thus opening new
      perspectives on supramolecular peptide dimerisation studies. 

PMID- 23963083
TI  - Ozone therapy in postgraduate theses in Egypt: systematic review.
AB  - BACKGROUND: Systematic reviews of the studies published in the major medical data
      bases have not shown solid support for the use of ozone therapy. Unpublished or
      grey literature, including postgraduate theses, may solve this controversy.
      OBJECTIVES: To review the postgraduate theses published in Egypt in order to
      assess the clinical safety and effectiveness of ozone therapy in specific medical
      conditions. METHODS: The databases of the Egyptian Universities' Library
      Consortium and the databases of each university were searched for postgraduate
      theses that evaluated ozone therapy as an intervention for any disease or
      condition in any age group, compared with any or no other intervention and
      published before September 2010. RESULTS: A total of 28 quasi trials were
      included. The theses did not report any safety issues in terms of ozone therapy.
      With respect to its effectiveness, the studies suggested some benefits of ozone
      in the treatment of dental infection and recovery, musculoskeletal disorders,
      diabetes mellitus, chronic diseases, and obstetrics and gynaecology. However, the
      number of studies included was small and they were of limited quality.
      CONCLUSION: There is insufficient evidence to recommend the use of ozone in the
      treatment of dental infections, in facilitating faster dental recovery after
      extraction or implantation, in diabetes mellitus, musculoskeletal disorders, or
      obstetrics and gynaecology.

PMID- 23963084
TI  - The impact of dietary and lifestyle factors on the risk of dental caries among
      young children in Qatar.
AB  - AIM: The aim of the current study was to investigate the relationship between
      dietary intake, type of feeding during infancy, other lifestyle and
      sociodemographic factors, and dental caries. DESIGN: A cross-sectional study.
      SETTING: The study was carried out on children younger than 16 years of age who
      visited Primary Health Care Centers. The study was carried out over a period from
      October 2010 to June 2011 in Qatar. PARTICIPANTS: A random sample of 1752
      children aged 6-15 years old who visited the Primary Health Care Centers was
      approached, and parents of 1284 children provided their consent and fulfilled the
      inclusion criteria (corresponding to a response rate of 73%). METHODS: The study
      was based on a questionnaire that included variables such as sociodemographic
      information, lifestyle, family history, and feeding patterns during infancy,
      information on oral hygiene practices, and clinical examination. The status of
      dental caries was recorded on the basis of the WHO criteria. RESULTS: The
      prevalence of dental caries [decayed, missed, or filled tooth (DMFT)] in the
      permanent dentition among children was 73% [95% confidence interval (CI): 71
      75%], with a mean DMFT value of 4.5 (SD: 4.2). The numbers of children consuming
      sea food, cod liver oil, and vitamin-D-fortified milk less than once a week were
      significantly higher in the dental caries group compared with those without
      caries (11.7 vs. 8.3%; P=0.05, 92.4 vs. 87.5%; P=0.005, and 10.6 vs. 6.3%;
      P=0.011, respectively). Multivariable logistic regression analysis showed that
      being female [adjusted odds ratio (OR): 1.41; 95% CI: 1.07-1.84], having a BMI
      greater than the 95th percentile versus less than the 85th percentile (adjusted
      OR: 2.12; 95% CI: 1.17-3.84), a monthly household income of at least 10 000 QAR
      (adjusted OR: 2.61; 95% CI: 1.69-4.02), consumption of cod liver oil less than
      once a week (adjusted OR: 2.13; 95% CI: 1.35-3.37), 1-year increase in age
      (adjusted OR: 1.05; 95% CI: 1.01-1.11), being formula fed during infancy
      (adjusted OR: 2.27; 95% CI: 1.59-3.21), and frequency of tooth brushing once a
      day or less (adjusted OR: 1.36; 95% CI: 1.01-1.83) were associated independently
      with the risk of dental caries among children in Qatar. CONCLUSION AND
      RECOMMENDATIONS: Being female, overweight or obese, and monthly household income
      higher than US$2747 (>=10,000 QAR) were independent risk factors for dental
      caries. However, consumption of cod liver oil (at least once a week) and
      frequency of tooth brushing (more than once a day) were protective against dental
      caries. Health awareness and education on frequent tooth brushing, adequate
      nutrition, and obesity prevention should be promoted to avoid dental caries among
      children.

PMID- 23963085
TI  - Frequency of Helicobacter pylori infection among Egyptian children presenting
      with gastrointestinal manifestations.
AB  - BACKGROUND AND AIMS: Recurrent abdominal pain (RAP) and other gastrointestinal
      (GI) symptoms are common complaints among children. The role of Helicobacter
      pylori in the causation of these complaints remains controversial. The aim of
      this study was to determine the frequency of H. pylori infection among children
      presenting with GI manifestations and to determine the most common clinical
      presentation of the infection in Egyptian children. PATIENTS AND METHODS: This
      prospective cross-sectional study included 150 consecutive patients aged 5-15
      years who presented to the outpatient clinic of Cairo University's Specialized
      Pediatric Hospital with GI complaints. Screening for H. pylori infection was
      performed using a 13C-urea breath test (13C-UBT), and in patients whose 13C-UBT
      was positive, diagnosis was confirmed by visualizing the bacterium in biopsy
      specimens obtained by GI endoscopy. RESULTS: RAP was the most frequent GI
      complaint of the study population (82%), followed by anorexia (6.7%), vomiting
      (6.7%), and chronic diarrhea (4.7%). Seventy percent of these patients were
      positive for the 13C-UBT. Ninety-one of the patients who complained of RAP had a
      positive 13C-UBT, whereas the remaining 32 patients who had RAP had a negative
      13C-UBT, a difference that was statistically significant (P=0.023). However, no
      statistically significant differences were found between the 13C-UBT result among
      patients with anorexia, vomiting, or diarrhea (P=0.153, 1.00, and 0.447,
      respectively). CONCLUSION AND RECOMMENDATIONS: Screening for H. pylori infection
      should be performed for school-aged children who have GI complaints, especially
      for those who complain of RAP.

PMID- 23963086
TI  - Opinion of community pharmacists on use of nonprescription medications in
      Alexandria, Egypt.
AB  - BACKGROUND: Many studies have reported the use of over-the counter (OTC) or
      nonprescription medications (medications that are available to consumers without
      a prescription) to be inappropriate and associated with risks to consumers. Among
      healthcare professionals, pharmacists have a key role in providing information
      and helping customers make a safe choice of nonprescription medicines. OBJECTIVE:
      This study aimed to measure the attitudes and beliefs of community pharmacists
      toward the use of nonprescription medications by Egyptian customers. SUBJECTS AND
      METHODS: A cross-sectional descriptive study was carried out among community
      pharmacies in Alexandria. A self-administered questionnaire was used to collect
      data from 335 pharmacists working in community pharmacies. RESULTS: The use of
      nonprescription medicine among patients/consumers was reported by 66.9% of
      pharmacists to have increased in the past 4 years and 94.1% of them considered
      such a use to be very serious or somewhat serious. Long-term or chronic use was
      cited by 76.7% of pharmacists as the most common reason for the widespread
      inappropriate use of nonprescription medications, and 82.4% of the pharmacists
      considered the most common contributing factor to be lack of knowledge of
      patients/customers about the active ingredients in a branded product. The most
      common medications enquired about by patients/consumers were those for cough,
      cold, or sore throat, as reported by 73.5% of pharmacists, whereas 79.4% of
      pharmacists reported that patients asked about how to use nonprescription drugs.
      Sixty percent of pharmacists reported that the main reason that
      patients/customers did not seek consultation for nonprescription medicines was
      that they believed that nonprescription medicines were safe, and 52.5% reported
      that patients believed that taking advice on how to use it was unnecessary. To
      learn about nonprescription medicine, 93.7% of pharmacists turned to drug product
      labeling. CONCLUSION AND RECOMMENDATIONS: Use of nonprescription drugs is a
      serious problem that has increased over the past few years. Long-term or chronic
      use of nonprescription medicine was the most common form of inappropriate use of
      nonprescription medications and lack of knowledge on the part of
      patients/customers about the active ingredient in a branded product was the most
      common factor contributing to its inappropriate use. Pharmacists should receive
      continuous professional education to increase their knowledge on and improve
      their practice of prescribing nonprescription medication; further, drug companies
      should be precise when disclosing information on OTC drug labels as the majority
      of pharmacists consult the drug label as a source of information about OTC.

PMID- 23963087
TI  - Patient safety in the operating room at a governmental hospital.
AB  - BACKGROUND: Patient safety is a fundamental principle of healthcare; it is a new
      healthcare discipline that emphasizes the reporting, analysis, and prevention of
      medical errors that often lead to adverse healthcare events. OBJECTIVES: The aim
      of this study is to aid any hospital in attaining better quality of patient care
      in the operating room (OR) by achieving patient safety according to the WHO
      safety guidelines. Specific objectives include the assessment of patient safety
      status in OR, the identification of hazards, and the assessment of risks that
      jeopardize this safety. MATERIALS AND METHODS: This is a descriptive
      observational study carried out in three ORs of a governmental hospital. The
      study was carried out from December 2008 through April 2009. A total of 100
      patients undergoing general surgical and urological surgical procedures were
      selected. The data collection tools included the WHO surgical safety checklist,
      nonstructured interviews, patient records, anesthesia checklist, and the risk
      assessment matrix. RESULTS: According to the WHO safety checklist, patients'
      safety was checked during three stages. During the 'sign in' stage, only 3% of
      all the patients had the operation site marked for surgery and an incident of a
      single wrong side surgery was recorded. There was a clear lack of communication
      between doctors and patients. During the 'time out' stage, 80% of surgeries
      lacked organized discussion among surgical team members for anticipated critical
      events. Prophylactic antibiotics were administered to 59% of patients undergoing
      surgeries. The 'sign out' stage was properly carried out in 100% of the
      procedures. Risk assessment in the 'sign in' stage showed six of 11 procedures
      leading to a major risk to patients. Also, in the 'time out' stage, three of
      eight procedures had a major risk. CONCLUSION AND RECOMMENDATIONS: To reach an
      optimal level of patient safety in the OR, it is recommended that the checklist
      should be implemented as part of the daily surgical routine. Identification of
      the hazards to which patients could be exposed and assessment of risks must be
      the ultimate goal in any OR.

PMID- 23963088
TI  - Workplace empowerment and organizational commitment among nurses working at the
      Main University Hospital, Alexandria, Egypt.
AB  - BACKGROUND: High-quality patient care depends on a nursing workforce that is
      empowered to provide care according to professional nursing standards. Numerous
      studies have established positive relationships between empowerment and important
      nursing outcomes such as work effectiveness, job satisfaction, and organizational
      commitment. PARTICIPANTS AND METHODS: A cross-sectional study design was used to
      assess the relationships between structural and psychological empowerment and
      their effects on hospital nurses' organizational commitment at the Main
      University Hospital in Alexandria governorate. The total number of nurses who
      participated in the study was 150 nurses, and four interview questionnaires were
      used to measure the study variables. RESULTS: The mean score percentage was
      higher for overall psychological empowerment (68.75%) than for overall structural
      empowerment (46.25%). There was a significant direct intermediate correlation
      between nurses' perceptions of overall structural and psychological work
      empowerment and their overall organizational commitment. There was no significant
      relationship between structural and psychological empowerment, organizational
      commitment and sociodemographic characteristics of nurses except for the overall
      organizational commitment with age (r=0.260), overall structural empowerment in
      the working department (P=0.031), and overall organizational commitment with
      nursing experience (significance=0.025). CONCLUSION AND RECOMMENDATIONS: Overall
      psychological empowerment achieved a higher mean score percentage compared with
      overall structural empowerment. Changing workplace structures is within the
      mandate of nurses' managers in their roles as advocates for and facilitators of
      high-quality care. The most significant opportunity for improvement is in the
      area of formal power, including flexibility, adaptability, creativity associated
      with discretionary decision-making, visibility, and centrality to organizational
      purpose and goals.

PMID- 23963089
TI  - Dietary pattern and blood pressure levels of adolescents in Sohag, Egypt.
AB  - BACKGROUND: Poor eating patterns formed early in life may lead to health problems
      in later years. These poor dietary habits are carried over into adolescence in
      Upper Egypt. The study aimed to assess the relationship between dietary pattern
      and blood pressure levels of adolescents in Sohag as one of Upper Egypt
      Governorates. PARTICIPANTS AND METHODS: A comparative cross-sectional study was
      carried out on 300 school students of both sexes between 12 and 18 years of age
      in Sohag. Schools from one educational district were stratified into private or
      public and boys or girls sectors. From each stratum, about 35-40 students were
      selected from one class at random. Data on sociodemographic characteristics,
      medical history, lifestyle, and dietary habits and intake were collected from
      each student. Anthropometric measurements and both systolic blood pressure (SBP)
      and diastolic blood pressure (DBP) were taken at the time of the interview.
      RESULTS: Hypertension was detected among 7.7% of the adolescents studied and
      prehypertension was detected among 34% of the adolescents. The entire studied
      sample consumed energy, protein, and sodium that exceeded their daily
      requirements, whereas their intake of potassium was less, with no statistically
      significant difference. The prehypertensive group consumed the highest daily
      intake of energy, macronutrients, sodium, and potassium. High BMI and low
      consumption of fruits and vegetables were associated with increased SBP and DBP.
      High consumption of chips was a predictor for increased SBP, whereas daily
      consumption of soft drinks was a predictor for increased DBP. CONCLUSION AND
      RECOMMENDATION: The study revealed significant association between the unhealthy
      dietary pattern and the risk of hypertension and prehypertension among
      adolescents in Sohag. Changes in their eating habits and dietary intake are
      highly recommended. Implementing a comprehensive nutrition promotion program has
      the potential to decrease the risk of hypertension during adulthood.

PMID- 23963090
TI  - Gestational diabetes mellitus: maternal and perinatal outcomes in King Khalid
      University Hospital, Saudi Arabia.
AB  - BACKGROUND: The prevalence of gestational diabetes mellitus (GDM) has increased
      worldwide, with a subsequent increase in the associated adverse pregnancy
      outcomes. OBJECTIVES: The objective of this study was to determine the prevalence
      of GDM and to compare the maternal and neonatal outcomes of women with GDM with
      nondiabetic women. MATERIALS AND METHODS: This is a retrospective cohort study
      investigating the maternal and the neonatal outcomes of women with GDM who
      delivered in King Khalid University Hospital as compared with the outcomes of
      nondiabetic women who delivered during the same period. The data were collected
      from the 1st of January to the 31st of December 2010 from the labor ward
      registry. The pregnancy outcomes of the women with GDM were compared with the
      outcomes of nondiabetic women who delivered during the same study period.
      RESULTS: Out of 3041 women who delivered during the study period, 569 (18.7%) had
      GDM and 2472 (81.3%) were not diabetic. Compared with the nondiabetic women,
      women with GDM were more likely to be delivered by emergency cesarean section
      (CS), odds ratio (OR) 1.30, 95% confidence intervals (CI) (1.02-1.66), or
      elective CS (OR 1.72, 95% CI 1.22-2.44, P<0.001). The neonates of the mothers
      with GDM were significantly heavier and more frequently macrosomic (OR 1.75, 95%
      CI 1.14-2.71, P<0.001). There was no significant difference between the two
      groups in the frequency of APGAR scores less than 7 in 5 min, preterm delivery at
      less than 37 weeks of gestation, or in the frequency of intrauterine fetal death.
      CONCLUSION: The prevalence of GDM in King Khalid University Hospital is among the
      highest in the world. GDM is associated with an increased risk for CS delivery
      and macrosomia.

PMID- 23963091
TI  - Prevalence and risk factors of sick building syndrome among office workers.
AB  - BACKGROUND: Sick building syndrome (SBS) is a group of symptoms relatively common
      among office workers; such symptoms could have an impact on the workers'
      productivity. The aim of this study is to measure the prevalence of SBS symptoms
      among office workers in the Faculty of Medicine, Ain Shams University, Cairo,
      Egypt, and to determine the possible risk factors. PARTICIPANTS AND METHODS: A
      cross-sectional study was carried out at the Ain Shams Faculty of Medicine
      including 826 workers. Data were collected through a self-administered
      questionnaire that included sociodemographic and occupational histories, work
      environment, and symptoms related to SBS. RESULTS: Fatigue and headache were the
      most prevalent symptoms (76.9 and 74.7%, respectively). Using univariate
      analysis, poor lighting, poor ventilation, lack of sunlight, absence of air
      currents, high noise, temperature, humidity, environmental tobacco smoke, use of
      photocopiers, and inadequate office cleaning were associated statistically with
      SBS symptoms (P<0.05). High work load and poor job satisfaction were also
      associated significantly with SBS symptoms (P<0.05). Logistic regression analysis
      showed that poor ventilation, poor lighting, environmental tobacco smoke, high
      temperature, poor job satisfaction, and inadequate office cleaning were the risk
      factors of SBS. CONCLUSION AND RECOMMENDATIONS: SBS was highly prevalent among
      office workers and was influenced by physical and psychosocial working
      conditions. Good ventilation, reducing room temperature, effective cleaning
      routines, providing proper lighting, restricting smoking in the workplace, and
      improving psychosocial working conditions are important ways to reduce SBS
      symptoms.

PMID- 23963092
TI  - Is it safe to eat raw seafood? Prevalence of Salmonella in some seafood products
      sold in Alexandria markets.
AB  - BACKGROUND: Salmonella is a significant microbial hazard in seafood. Salmonella
      contaminated seafood usually looks and smells normal; it is therefore essential
      that every effort is made toward the rapid detection of Salmonella as an
      important criterion in quality control of seafood. AIMS: This study aims to
      determine the percentage of Salmonella in some Egyptian seafood sold in
      Alexandria markets and to study the validity of Chromagar Salmonella Plus (CASP)
      agar versus xylose lysine desoxycholate and Salmonella-Shigella agar for the
      isolation and identification of Salmonella in seafood. MATERIALS AND METHODS: Two
      hundred and twenty-five samples of three seafood types, shrimp, gandofli, and
      river mussel (om-elkhloul) were studied. Samples were selectively enriched in
      Rappaport-Vassiliadis and tetrathionate broth, and then plated onto the
      aforementioned plating media for the detection of Salmonella. RESULTS: In total,
      Salmonella was detected in 9.8% of the samples. The sensitivity and specificity
      of the media used varied according to the media and enrichment broth combinations
      used. The CASP and Rappaport-Vassiliadis combination yielded the best
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy of 95.45, 100, 100, 99.5, and 99.5%, respectively. CONCLUSION AND
      RECOMMENDATION: CASP was more accurate than xylose lysine desoxycholate and
      Salmonella-Shigella in the detection of Salmonella from seafood samples. We
      recommend that CASP medium should be tested against more Salmonella-positive
      samples before it is used as a screening plating medium for Salmonella in
      seafood.

PMID- 23963093
TI  - Using click chemistry to measure the effect of viral infection on host-cell RNA
      synthesis.
AB  - Many RNA viruses have evolved the ability to inhibit host cell transcription as a
      means to circumvent cellular defenses. For the study of these viruses, it is
      therefore important to have a quick and reliable way of measuring transcriptional
      activity in infected cells. Traditionally, transcription has been measured either
      by incorporation of radioactive nucleosides such as (3)H-uridine followed by
      detection via autoradiography or scintillation counting, or incorporation of
      halogenated uridine analogs such as 5-bromouridine (BrU) followed by detection
      via immunostaining. The use of radioactive isotopes, however, requires
      specialized equipment and is not feasible in a number of laboratory settings,
      while the detection of BrU can be cumbersome and may suffer from low sensitivity.
      The recently developed click chemistry, which involves a copper-catalyzed
      triazole formation from an azide and an alkyne, now provides a rapid and highly
      sensitive alternative to these two methods. Click chemistry is a two step process
      in which nascent RNA is first labeled by incorporation of the uridine analog 5
      ethynyluridine (EU), followed by detection of the label with a fluorescent azide.
      These azides are available as several different fluorophores, allowing for a wide
      range of options for visualization. This protocol describes a method to measure
      transcriptional suppression in cells infected with the Rift Valley fever virus
      (RVFV) strain MP-12 using click chemistry. Concurrently, expression of viral
      proteins in these cells is determined by classical intracellular immunostaining.
      Steps 1 through 4 detail a method to visualize transcriptional suppression via
      fluorescence microscopy, while steps 5 through 8 detail a method to quantify
      transcriptional suppression via flow cytometry. This protocol is easily adaptable
      for use with other viruses.

PMID- 23963094
TI  - A convenient method to construct (Z)-oxazines via 6-exo-dig iodocyclization and
      synthesis of indolin-3-one.
AB  - An efficient regio-, stereo- and chemo-specific synthesis of 1,3-benzoxazines via
      6-exo-dig cyclization to afford the Z-isomer is reported. The structure and
      connectivity were confirmed unambiguously on the basis of (1)H NMR, NOESY, and
      ORTEP. Furthermore, DFT studies revealed that the Z-isomer was more stable than
      the E-isomer. Iodine substituted 1,3-benzoxazines were very useful precursors for
      cross coupling reactions. Suzuki reaction was carried out successfully and the
      resulting product was transformed to 1-(4-nitrobenzoyl)-2,2-diphenylindolin-3-one
      in the presence of a Lewis acid. 

PMID- 23963095
TI  - Stable high efficiency dye-sensitized solar cells based on a cobalt polymer gel
      electrolyte.
AB  - A tris(2,2'-bipyridine)cobalt(II)/(III) based polymer gel electrolyte has been
      successfully applied in conjunction with an organic carbazole dye in the
      construction of stable dye-sensitized solar cells with an energy conversion
      efficiencies of 8.7% and 10% at 1 sun and 0.1 sun light intensity.

PMID- 23963096
TI  - Difference in fibrinolytic capacity in young patients with venous thrombosis or
      ischaemic stroke.
AB  - Many recent studies focus on the common pathophysiological mechanisms and risk
      factors for arterial and venous thrombosis. We investigated the hypothesis that
      fibrinolytic capacity is similar in patients with ischaemic stroke and venous
      thromboembolism. Retrospective study of 604 consecutive patients (age <50 years)
      referred to systematic thrombophilia testing at a single regional centre. The
      thrombophilia test included clinical variables, genetic polymorphisms, biomarkers
      of coagulation and a global assay of fibrinolysis that tested the patient's blood
      fibrinolytic capacity by application of the euglobulin fraction of plasma to a
      preformed clot of plasminogen-rich bovine fibrin. The patients with venous
      thromboembolism (n = 284) were slightly younger (32.3 vs. 33.9 years; <0.01) than
      those with ischaemic stroke (n = 320), had a significantly higher prevalence of
      obesity (28 vs. 18%; P < 0.01), higher plasminogen activator inhibitor 1 (PAI-1)
      activity (12.3 vs. 11.1 IU/ml; P = 0.049) and a significantly lower fibrinolytic
      capacity (3.4 vs. 3.9 IU/ml; P < 0.01). The lower fibrinolytic capacity in
      patients with venous thromboembolism was also observed in the subgroup of
      patients with PAI-1 activity within the normal range (n = 430, 3.7 vs. 4.1IU/ml;
      P < 0.01). After adjustment for age, BMI, fibrinogen concentration, PAI-1
      activity and tissue plasminogen activator activity, fibrinolytic capacity still
      differed significantly between the two groups. Our results indicate that the
      capacity for fibrinolysis is lower in young patients with venous thromboembolism
      than ischaemic stroke, suggesting a different mechanistic role of fibrinolysis in
      arterial and venous thromboembolism. 

PMID- 23963097
TI  - Factor VIII mutations and inhibitor formation in a southern Brazilian population.
AB  - A total of 110 patients with severe (n = 43), moderate (n = 15) or mild (n = 52)
      haemophilia A were studied in relation to their F8 gene mutation and inhibitor
      status. Nineteen percentage of them had anti-factor VIII antibodies. Significant
      heterogeneity in inhibitor prevalence considering the location of the patients'
      mutation was found, with higher frequencies in carriers of mutations in the C1
      and B domains. Twelve specific mutations showed associations with inhibitor
      formation, seven deletions, two nonsense, two insertions and one missense
      changes. Bioinformatic analysis of the missense mutation confirmed the formation
      of a B-cell epitope in the protein. This information is important for comparative
      purposes with series of other ethnic constitutions, as well as for individual
      prevention of this serious clinical problem in the patient population. 

PMID- 23963098
TI  - The relationship between hemoglobin A1C in youth with type 1 diabetes and chaos
      in the family household.
AB  - PURPOSE: The purpose of the study was to examine how physical and social
      environments, as measured by household chaos, affect the diabetes control (i.e.,
      A1C) in youth with type 1 diabetes (T1DM). METHODS: One hundred and four patients
      (53 male, 51 female) with T1DM (aged 1-13 years) and their caregivers were
      recruited from a diabetes clinic at a Midwestern children's hospital. The
      caregivers completed a demographic questionnaire as well as a questionnaire
      pertaining to chaos in the household. A medical record review at baseline and 3-
      and 6-month follow-up was also conducted. RESULTS: Results found that above and
      beyond the demographic covariates, there still remained a significant
      relationship between household chaos and glycemic control. Those who scored more
      than 1 standard deviation above the mean Confusion, Hubbub, and Order Scale
      (CHAOS) measure score showed significantly worse glycemic control at 6-month
      follow-up. CONCLUSIONS: This study demonstrated the relationship of family
      environment and glycemic control for youth with T1DM. The findings highlight the
      need to individually assess the youth's home environment to promote diabetes
      management and care during clinic visits.

PMID- 23963099
TI  - Change in health literacy over 2 years in older adults with diabetes.
AB  - PURPOSE: The purpose of this study was to evaluate the stability of health
      literacy in adults with diabetes over time. Understanding the dynamic nature of
      health literacy is important when tailoring health messages, especially those
      targeted at the management of chronic health conditions. METHOD: This was a
      descriptive longitudinal study of 751 adults with diabetes randomly selected from
      primary care practices in the Vermont Diabetes Information System study between
      July 2003 and December 2007. Participants were interviewed and completed
      questionnaires upon entrance into the study and again 24 months later. Health
      literacy was measured with the Short Test for Functional Health Literacy of
      Adults. Participants also completed the SF-12 and the Self-Administered
      Comorbidity Questionnaire and self-reported their sex, income, education, marital
      status, race/ethnicity, health insurance, duration of diabetes, and problems with
      vision. RESULTS: A significant decrease in health literacy was noted over 24
      months. The largest decrease was in adults >=65 years of age and those with
      higher physical function at baseline. Smaller declines were noted for women and
      participants who were white, higher educated, poly-pharmacy users, and with fair
      to excellent vision. CONCLUSIONS: Health literacy exhibits decline with
      increasing age among adults with diabetes. Individual variability in health
      literacy has implications for the best timing and approach to provide self
      management education and support.

PMID- 23963100
TI  - Ultrasensitive and recyclable SERS substrate based on Au-decorated Si nanowire
      arrays.
AB  - Metallic nanoparticle (NP) decorated silicon nanowire (SiNW) heterostructures
      show significant promise in enhanced optical and opto-electrical properties due
      to the coupling of surface plasmon to nanowires. Here, recyclable Au-decorated
      silicon nanowire arrays (Au-SiNWAs) as surface-enhanced Raman scattering (SERS)
      substrates were successfully fabricated by a simple galvanic displacement
      reaction. The influence of different average size and aggregation level of Au NPs
      on SERS activity was explored. The SERS activity of the substrates strongly
      depends on the average size and aggregation level of Au NPs on the surface of the
      SiNWs, and the most optimal size and separation of AuNPs on the SiNWs can be
      achieved by controlling the reaction time. The optimized Au-SiNWA substrate
      exhibits ultrahigh sensitivity with an enhancement factor of 10(9), and is able
      to detect the analyte molecule at a concentration as low as 10(-11) M. More
      importantly, the SERS substrate is recyclable, as enabled by a self-cleaning
      function due to UV light photocatalytic degradation of the analyte molecules. The
      high sensitivity and recyclability of the Au-SiNWA SERS substrate is demonstrated
      by the detection of a model molecule rhodamine B (RhB). Our studies show that the
      unique Au-SiNWA SERS substrates have significant potential to put SERS into wider
      application. 

PMID- 23963102
TI  - Tamsulosin and tolterodine in the medical expulsive therapy for intramural
      ureteral stones with vesical irritability: a prospective randomized study.
AB  - We performed a randomized, prospective study to assess the possible role of
      combined tamsulosin and tolterodine therapy for the relief of vesical
      irritability and in facilitating the spontaneous expulsion of intramural ureteral
      stones. Patients were randomized to one of three treatment groups. Treatment
      group 1 patients received tamsulosin 0.4 mg/day, group 2 patients received
      tamsulosin 0.4 mg/day plus tolterodine 2 mg (twice a day), and group 3 patients
      received tolterodine 2 mg (twice a day). Subjects rated the urgency associated
      with each micturition using the Urinary Sensation Scale. Pain descriptions were
      recorded by the patients using the Visual Analog Scale. Stone expulsion was
      observed in 30 patients in group 1, 29 patients in group 2 and 18 patients in
      group 3. Kaplan-Meier curves were plotted to access the expulsion rate of each
      group over time. A significant difference was shown for the expulsion rate
      between the tolterodine group and the other two groups. (P = 0.003 by log rank
      test). Average time to expulsion for groups 1, 2 and 3 was 7.62 +/- 2.42, 7.79 +/
      2.11 and 10.57 +/- 2.71 days, respectively (P = 0.000). In groups 1, 2 and 3,
      the mean number of pain episodes was 2.27 +/- 0.91, 1.39 +/- 1.34 and 1.38 +/-
      1.20, respectively (P = 0.023). Treatment with tamsulosin and tolterodine appears
      to be beneficial in intramural ureteral stone clearance, particularly in
      intramural ureter stone with symptoms of vesical irritability. 

PMID- 23963103
TI  - Predictors of excessive renal displacement during access in percutaneous
      nephrolithotomy: a randomized clinical trial.
AB  - To determine the magnitude of renal displacement (a major cause of access failure
      or loss) during the renal access steps in percutaneous nephrolithotomy (PCNL),
      investigate predictors of excessive renal displacement, and compare the effect of
      one-stage versus gradual dilation on renal displacement during access. Sixty-six
      adult patients undergoing PCNL were randomized into two groups containing 33
      patients each: Group 1 underwent gradual tract dilation with Alken metal
      dilators, and Group 2 received one-stage tract dilation. In each patient, maximum
      renal displacement was measured in three planes (cephalocaudal, anteroposterior,
      and mediolateral) during the three access steps (needle puncture, Alken guide
      insertion, and dilator advancement). The patients' demographic data and
      intraoperative parameters were compared. In both groups, net renal displacement
      during the three access steps was in the cephalad, medial, and anterior
      directions. There were no significant differences in the magnitude of renal
      displacement in patients with gradual versus one-stage tract dilation. Renal
      displacement was significantly more pronounced in all planes and in all access
      steps in female patients and in those with no previous history of open stone
      surgery on the ipsilateral kidney. High body mass index (BMI) showed a
      significant negative correlation with cephalad and anterior renal displacement,
      but not with medial displacement. Three-dimensional movement of the kidney during
      percutaneous access in PCNL is similar when gradual versus one-stage tract
      dilation is used. Inherent patient characteristics, such as female sex, BMI, and
      a previous ipsilateral flank scar are major determinants of the magnitude of
      renal displacement during the PCNL access steps. 

PMID- 23963104
TI  - The role of calcium phosphate in the development of Randall's plaques.
AB  - Results of research carried out during recent years have shown that papillary
      subepithelial and intratubular deposits of calcium phosphate have important roles
      in the formation of calcium oxalate stones. In this article, the mechanisms of
      calcium oxalate stone formation are briefly reviewed and the background to
      formation of Randall's plaques type I and II discussed. Although some of the
      conclusions are difficult to prove, it stands to reason that improved
      understanding of how calcium phosphate is deposited in the interstitial tissue as
      well as in the collecting ducts will be of great importance for design of
      rational and individualized recurrence prevention. 

PMID- 23963101
TI  - Chinese SLE Treatment and Research group (CSTAR) registry: I. Major clinical
      characteristics of Chinese patients with systemic lupus erythematosus.
AB  - The Chinese systemic lupus erythematosus (SLE) treatment and research group
      (CSTAR) provides major clinical characteristics of SLE in China and establishes a
      platform to provide resources for future basic and clinical studies. CSTAR
      originated as a multicentre, consecutive, and prospective design. The data were
      collected online from 104 rheumatology centers, which covered 30 provinces in
      China. The registered patients were required to meet four or more of the American
      College of Rheumatology (ACR) criteria for the classification of SLE. All CSTAR
      centers use the same protocol-directed methods to provide uniform evaluations,
      which included demographic data, clinical features, laboratory examinations, and
      disease activity evaluations. The patient samples, including DNA samples and
      sera, were also collected for further quality controls and additional studies.
      Preliminary analysis from 2104 baseline evaluations was available for this
      analysis. Of 1914 female and 190 male patients (F:M=10.1), the mean age at onset
      was 29.2 y with confirmed diagnosis one year later at the age of 30.3 y. Eighty
      four (4.2%) of 2002 patients had a family history of rheumatic diseases,
      including 34 (1.7%) cases with SLE. In addition, one hundred and seven (5.2%)
      abnormal pregnancies were recorded among 2026 experiences. The characteristics of
      the CSTAR cohort were compared to similarly sized cohorts from other studies. We
      found that 56.1% of patients presented with concurrent hematological disorders
      compared to only 18.2% of European patients. Moreover, 47.4% of patients
      presented with nephropathy compared to 27.9% of European patients. Conversely,
      neurological manifestations were only seen in 4.8% of Chinese SLE patients
      compared to 19.4% of European patients, 12.1% of U.S. patients, 22.8% of
      Malaysian patients and 26.4% of Latin Americans. Pulmonary arterial hypertension
      and interstitial lung diseases were complications identified in 3.8% and 4.2% of
      Chinese lupus patients, respectively. The CSTAR registry has provided
      epidemiological data and phenotypes of Chinese patients with SLE, and has
      demonstrated several differences between ethnicities. Clinical data and biologic
      samples would be valuable resources for future translational studies with
      national and international collaboration.

PMID- 23963105
TI  - Design and Coordination Kinematics of an Insertable Robotic Effectors Platform
      for Single-Port Access Surgery.
AB  - Single port access surgery (SPAS) presents surgeons with added challenges that
      require new surgical tools and surgical assistance systems with unique
      capabilities. To address these challenges, we designed and constructed a new
      insertable robotic end-effectors platform (IREP) for SPAS. The IREP can be
      inserted through a O15 mm trocar into the abdomen and it uses 21 actuated joints
      for controlling two dexterous arms and a stereo-vision module. Each dexterous arm
      has a hybrid mechanical architecture comprised of a two-segment continuum robot,
      a parallelogram mechanism for improved dual-arm triangulation, and a distal wrist
      for improved dexterity during suturing. The IREP is unique because of the
      combination of continuum arms with active and passive segments with rigid
      parallel kinematics mechanisms. This paper presents the clinical motivation,
      design considerations, kinematics, statics, and mechanical design of the IREP.
      The kinematics of coordination between the parallelogram mechanisms and the
      continuum arms is presented using the pseudo-rigid-body model of the beam
      representing the passive segment of each snake arm. Kinematic and static
      simulations and preliminary experiment results are presented in support of our
      design choices.

PMID- 23963106
TI  - Performance of English stop smoking services in first 10 years: analysis of
      service monitoring data.
AB  - OBJECTIVES: To analyse the performance of the English Stop Smoking Services from
      2001/02 to 2010/11. DESIGN: Analysis of national service monitoring data.
      SETTING: England. PARTICIPANTS: Smokers recorded as having been treated by
      English stop smoking services between April 2001 and March 2011. MAIN OUTCOME
      MEASURES: Annual figures for the number of quit dates set (throughput), the
      percentage of these that led to biochemically verified abstinence after four
      weeks (four week quit rate), and the "impact" in terms of the number of four week
      quitters beyond those who it is estimated would have stopped with only a
      prescription for smoking cessation treatment; characteristics of smokers being
      treated, medication used, and mode of delivery (for example, one to one, group
      based); variability across local services in throughput, four week quit rates,
      and impact for 2010/11. RESULTS: Throughput rose from 227,335 in 2001/02 to
      787,527 (8% of all smokers) in 2010/11. The percentage of four week quitters
      declined slightly from 35% to 34%. Impact rose from 22,933 four week quitters
      created in 2001/02 to 72,411 in 2010/11 (corresponding to an estimated 21,723 12
      month quitters). The services were successful in reaching disadvantaged smokers;
      54% (n = 425,684) were in receipt of free prescriptions in 2010/11. Substantial
      variation existed across local services in throughput, success rates, and impact.
      CONCLUSIONS: The English stop smoking services have had an increasing impact in
      helping smokers to stop in their first 10 years of operation and have
      successfully reached disadvantaged groups. However, performance across local
      services has varied considerably.

PMID- 23963107
TI  - I blew the whistle on the government's disability assessments.

PMID- 23963108
TI  - Prioritising existing donors to receive organs would boost donation from ethnic
      minorities.

PMID- 23963110
TI  - Letter from the editor. Moral distress among health care professionals.

PMID- 23963109
TI  - 8-hydroxy-2'-deoxyguanosine in colorectal adenocarcinoma--is it a result of
      oxidative stress?
AB  - BACKGROUND: 8-hydroxy-2'-deoxyguanosine (8-OHdG) is one of the most abundant
      oxidatively modified lesions in DNA and is a marker of the oxidative stress. 8
      OHdG is a mutagenic lesion and it can mispair with adenine, causing G:C->T: A
      transversion. Our task was to determine the 8-OHdG level in patients with
      colorectal adenocarcinoma directly in tumor tissues and corresponding normal
      mucosa. MATERIAL/METHODS: Samples of tumor tissues and corresponding normal
      mucosa of 47 patients undergoing surgery for colorectal cancer were analyzed. DNA
      was isolated from both tumor and normal tissues. Then, DNA was hydrolyzed to
      nucleotides using nuclease P1 and alkaline phosphatase. The 8-OHdG and 2'-dG (2'
      deoxyguanosine) were determined in hydrolysates by high-performance liquid
      chromatography (HPLC) with electrochemical (EC) and UV detector. RESULTS: The
      levels of 8-OHdG in colorectal adenocarcinoma tissues were higher than in
      corresponding normal mucosa. No significant differences were shown in 8-OHdG
      levels in the cancerous and cancer-free tissues between age and sex and stages
      A/B and C/D of Duke's classification. CONCLUSIONS: 8-OHdG reflects the local
      oxidative stress in colon adenocarcinoma tissue together with ageing processes,
      but not the intensity of tumorigenesis itself. Because of many factors that could
      influence the oxidative modification of DNA bases, its role as a diagnostic
      and/or prognostic factor in colon adenocarcinoma seems to be limited.

PMID- 23963111
TI  - Legal briefs.
AB  - This column provides executive summaries of developments in legal and regulatory
      issues related to healthcare, lists a bibliography of pertinent healthcare law
      related articles, and discusses interesting health law court decisions. 

PMID- 23963112
TI  - Moral distress among healthcare professionals at a health system.
AB  - Moral distress is increasingly recognized as a problem affecting healthcare
      professionals. If not addressed, it may create job dissatisfaction, withdrawal
      from the moral dimensions of patient care, or even leaving the profession. Using
      the 21-Moral Distress Scale-Revised to assess moral distress, 323 surveys were
      received from 5 healthcare disciplines. The overall results showed that all
      disciplines experienced moderate to high actual moral distress, related to
      similar and/or different patient care situations. 

PMID- 23963116
TI  - Heteronemin, a marine sponge terpenoid, targets TDP-43, a key factor in several
      neurodegenerative disorders.
AB  - Trans-activation response DNA-binding protein of 43 kDa (TDP-43), a key factor in
      several neurodegenerative conditions, was discovered as a novel target of
      heteronemin by chemical proteomics. Combining bio-physical orthogonal approaches
      with biological analysis, heteronemin was found to influence the binding of TDP
      43-cognate nucleic acids and to modulate the TDP-43 aggregation state and its
      cellular localization. 

PMID- 23963114
TI  - Coordinated targeting of the EGFR signaling axis by microRNA-27a*.
AB  - Epidermal growth factor receptor (EGFR) has been characterized as a critical
      factor in the development and progression of multiple solid tumors, including
      head and neck squamous cell carcinoma (HNSCC). However, monotherapy with EGFR
      specific agents has not been as dramatic as preclinical studies have suggested.
      Since complex regulation of the EGFR signaling axis might confound current
      attempts to inhibit EGFR directly, we searched for microRNAs (miRNAs) that may
      target the EGFR signaling axis. We identified miR-27a (miR-27a-3p) and its
      complementary or star (*) strand, miR-27a* (miR-27a-5p), as novel miRNAs
      targeting EGFR, which were significantly downregulated in multiple HNSCC cell
      lines. Analysis of human specimens demonstrated that miR-27a* is significantly
      underexpressed in HNSCC as compared to normal mucosa. Increased expression of miR
      27a* in HNSCC produced a profound cytotoxic effect not seen with miR-27a.
      Analysis for potential targets of miR-27a* led to the identification of AKT1
      (protein kinase B) and mTOR (mammalian target of rapamycin) within the EGFR
      signaling axis. Treatment with miR-27a* led to coordinated downregulation of
      EGFR, AKT1 and mTOR. Overexpression of EGFR signaling pathway components
      decreased the overall effect of miR-27a* on HNSCC cell viability. Constitutive
      and inducible expression of miR-27a* in a murine orthotopic xenograft model of
      oral cavity cancer led to decreased tumor growth. Direct intratumoral injection
      of miR-27a* inhibited tumor growth in vivo. These findings identify miR-27a* as a
      functional star sequence that exhibits novel coordinated regulation of the EGFR
      pathway in solid tumors and potentially represents a novel therapeutic option. 

PMID- 23963117
TI  - Impulsivity and risk taking in bipolar disorder and schizophrenia.
AB  - Impulsive risk taking contributes to deleterious outcomes among clinical
      populations. Indeed, pathological impulsivity and risk taking are common in
      patients with serious mental illness, and have severe clinical repercussions
      including novelty seeking, response disinhibition, aggression, and substance
      abuse. Thus, the current study seeks to examine self-reported impulsivity
      (Barratt Impulsivity Scale) and performance-based behavioral risk taking (Balloon
      Analogue Risk Task) in bipolar disorder and schizophrenia. Participants included
      68 individuals with bipolar disorder, 38 with schizophrenia, and 36 healthy
      controls. Self-reported impulsivity was elevated in the bipolar group compared
      with schizophrenia patients and healthy controls, who did not differ from each
      other. On the risk-taking task, schizophrenia patients were significantly more
      risk averse than the bipolar patients and controls. Aside from the diagnostic
      group differences, there was a significant effect of antipsychotic (AP)
      medication within the bipolar group: bipolar patients taking AP medications were
      more risk averse than those not taking AP medications. This difference in risk
      taking because of AP medications was not explained by history of psychosis.
      Similarly, the differences in risk taking between schizophrenia and bipolar
      disorder were not fully explained by AP effects. Implications for clinical
      practice and future research are discussed. 

PMID- 23963119
TI  - Seasonal variations of polychlorinated biphenyls in surface soils and air-soil
      exchange in Bursa, Turkey.
AB  - This study investigates the seasonality of polychlorinated biphenyl (PCB) levels
      in soils of Bursa city located in northwestern Turkey. Forty-three soil samples
      were collected each season during a 1-year period. Air and soil samples were
      collected concurrently 3 or 3 times in a month during a 1-year monitoring period
      from 2 of the 43 locations. The samples were analyzed for 83 PCB congeners. Flux
      levels, fugacity fraction (ff) levels, and net flux levels of PCB congeners were
      calculated for 2 specific regions. The influence of humic substance and total
      organic carbon content of soil on PCB levels was also examined. The mean
      concentrations of the total PCBs were 1275 +/- 1120, 4075 +/- 2740, 2185 +/-
      2010, and 1150 +/- 1540 pg/g dry weight in spring, summer, autumn, and winter
      seasons, respectively. Four- and 5- CBs were the most abundant homologue groups
      in soils, and their contribution to the total was 55 %. PCB-74, followed by PCB
      153, was the dominant congener. Air and soil PCB levels increased together with
      the soil temperature suggesting the influence of instantaneous air-soil exchange
      toward the equilibrium conditions. Flux and ff levels also showed a positive
      significant correlation with soil temperature. Flux levels were mostly positive
      for the 2 regions indicating volatilization from soil to air. 

PMID- 23963118
TI  - Learning not to fear: neural correlates of learned safety.
AB  - The ability to recognize and properly respond to instances of protection from
      impending danger is critical for preventing chronic stress and anxiety-central
      symptoms of anxiety and affective disorders afflicting large populations of
      people. Learned safety encompasses learning processes, which lead to the
      identification of episodes of security and regulation of fear responses. On the
      basis of insights into the neural circuitry and molecular mechanisms involved in
      learned safety in mice and humans, we describe learned safety as a tool for
      understanding neural mechanisms involved in the pathomechanisms of specific
      affective disorders. This review summarizes our current knowledge on the
      neurobiological underpinnings of learned safety and discusses potential
      applications in basic and translational neurosciences. 

PMID- 23963120
TI  - Bioaccumulation of arsenic and cadmium in birch and lime from the Bor region.
AB  - Copper production in the Bor region (east Serbia) during the last 100 years has
      influenced the quality of soil, water, and air. This pollution has endangered not
      only the biotope but all living organisms, including humans. Contents of arsenic
      (As) and cadmium (Cd) were analyzed in Betula sp. (birch) and Tillia sp. (lime)
      within the Bor region with the aim to investigate the bioaccumulation of these
      highly toxic, nonessential trace elements in selected plants, which may be
      important for biomonitoring and bioremediation purposes. The results of
      statistical data analysis showed that several factors influenced the
      bioaccumulation of trace elements in the examined plants, of which soil pH, soil
      content, and mechanism of accumulation were the main factors. The greatest As and
      Cd concentrations were found in plant material from the Bor center sampling site
      in the urban/industrial zone, which is in close proximity to the pollution
      source, due to the greatest metal concentrations in soil and the lowest soil pH.
      The low values of biological accumulation coefficients (bioconcentration factor
      <1, mobility ratio <1) pointed to a low rate of uptake and accumulation of As and
      Cd in lime and birch. Trace elements showed different patterns of behavior and
      accumulation in the trees. Lime showed a high ability of assimilation through
      leaves, whereas birch showed a better potential to express a linear correlation
      between concentrations in plant parts and soil. 

PMID- 23963121
TI  - Predictors of 30-day readmission after intracerebral hemorrhage: a single-center
      approach for identifying potentially modifiable associations with readmission.
AB  - OBJECTIVE: To determine whether patient's demographics or severity of illness
      predict hospital readmission within 30 days following spontaneous intracerebral
      hemorrhage, to identify readmission associations that may be modifiable at the
      single-center level, and to determine the impact of readmission on outcomes.
      DESIGN: We collected demographic, clinical, and hospital course data for
      consecutive patients with spontaneous intracerebral hemorrhage enrolled in an
      observational study. Readmission within 30 days was determined retrospectively by
      an automated query with manual confirmation. We identified the reason for
      readmission and tested for associations between readmission and functional
      outcomes using modified Rankin Scale (a validated functional outcome measure from
      0, no symptoms, to 6, death) scores before intracerebral hemorrhage and at 14
      days, 28 days, and 3 months after intracerebral hemorrhage. SETTING: Neurologic
      ICU of a tertiary care hospital. PATIENTS: Critically ill patients with
      spontaneous intracerebral hemorrhage. INTERVENTIONS: Patients received standard
      critical care management for intracerebral hemorrhage. MEASUREMENTS AND MAIN
      RESULTS: Of 246 patients (mean age, 65 yr; 51% female), 193 patients (78%)
      survived to discharge. Of these, 22 patients (11%) were readmitted at a median of
      9 days (interquartile range, 4-15 d). The most common readmission diagnoses were
      infections after discharge (n = 10) and vascular events (n = 6). Age, history of
      stroke and hypertension, severity of neurologic deficit at admission, Acute
      Physiology and Chronic Health Evaluation score, ICU and hospital length of stay,
      ventilator-free days, days febrile, and surgical procedures were not predictors
      of readmission. History of coronary artery disease was associated with
      readmission (p = 0.03). Readmitted patients had similar modified Rankin Scale and
      severity of neurologic deficit at 14 days but higher (worse) modified Rankin
      Scale scores at 3 months (median [interquartile range], 5 [3-6] vs 3 [1-4]; p =
      0.01). CONCLUSIONS: Severity of illness and hospital complications were not
      associated with 30-day readmission. The most common indication for readmission
      was infection after discharge, and readmission was associated with worse
      functional outcomes at 3 months. Preventing readmission after intracerebral
      hemorrhage may depend primarily on optimizing care after discharge and may
      improve functional outcomes at 3 months.

PMID- 23963122
TI  - ICU occupancy and mechanical ventilator use in the United States.
AB  - OBJECTIVES: Detailed data on occupancy and use of mechanical ventilators in U. S.
      ICU over time and across unit types are lacking. We sought to describe the hourly
      bed occupancy and use of ventilators in U.S. ICUs to improve future planning of
      both the routine and disaster provision of intensive care. DESIGN: Retrospective
      cohort study. We calculated mean hourly bed occupancy in each ICU and hourly bed
      occupancy for patients on mechanical ventilators. We assessed trends in overall
      occupancy over the 3 years. We also assessed occupancy and mechanical ventilation
      rates across different types and sizes of ICUs. SETTING: Ninety-seven U.S. ICUs
      participating in Project IMPACT from 2005 to 2007. PATIENTS: A total of 226,942
      consecutive admissions to ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Over the 3 years studied, total ICU occupancy ranged from 57.4% to 82.1%
      and the number of beds filled with mechanically ventilated patients ranged from
      20.7% to 38.9%. There was no change in occupancy across years and no increase in
      occupancy during influenza seasons. Mean hourly occupancy across ICUs was 68.2%
      +/- 21.3% (SD) and was substantially higher in ICUs with fewer beds (mean, 75.8%
      +/- 16.5% for 5-14 beds vs 60.9% +/- 22.1% for 20+ beds, p = 0.001) and in
      academic hospitals (78.7% +/- 15.9% vs 65.3% +/- 21.3% for community not-for
      profit hospitals, p < 0.001). More than half of ICUs (53.6%) had 4+ beds
      available more than half the time. The mean percentage of ICU patients receiving
      mechanical ventilation in any given hour was 39.5% (+/- 15.2%), and a mean of
      29.0% (+/- 15.9%) of ICU beds were filled with a patient on a ventilator.
      CONCLUSIONS: Occupancy of U.S. ICUs was stable over time, but there is uneven
      distribution across different types and sizes of units. Only three of 10 beds
      were filled at any time with mechanically ventilated patients, suggesting
      substantial surge capacity throughout the system to care for acutely critically
      ill patients.

PMID- 23963124
TI  - Risk of developing pneumonia is enhanced by the combined traits of
      fluoroquinolone resistance and type III secretion virulence in respiratory
      isolates of Pseudomonas aeruginosa.
AB  - OBJECTIVES: To determine the differential association of host characteristics,
      antimicrobial resistance, and type III secretion system virulence of Pseudomonas
      aeruginosa isolates with respiratory syndromes in hospitalized adult patients.
      DESIGN: Retrospective, cohort study. SETTING: Community teaching hospital.
      PATIENTS: Two hundred eighteen consecutive adult patients with respiratory
      culture positive for P. aeruginosa between January 2005 to January 2010.
      INTERVENTIONS: Medical charts were reviewed to obtain demographic, laboratory,
      radiographic, and clinical information. Isolates were assayed by polymerase chain
      reaction for genes encoding the type III secretion system effectors (ExoU, ExoS,
      and PcrV) and for strain relatedness using randomly amplified polymorphic DNA
      analysis. Levofloxacin susceptibility was determined by broth microdilution.
      Patients were grouped by colonization, bronchitis, or pneumonia and were compared
      for differential risk of developing the clinical syndrome with respect to host
      and microbial characteristics. MEASUREMENTS AND MAIN RESULTS: Half of the study
      cohort (54%, 117 of 218) had pneumonia, 32% (70 of 218) had bronchitis, and 14%
      (31 of 218) had colonization; in-hospital mortality was 35%, 11%, and 0%,
      respectively. Host factors strongly associated with pneumonia development were
      residence in long-term care facility, healthcare-associated acquisition of P.
      aeruginosa, higher Acute Physiology and Chronic Health Evaluation II score,
      presence of enteral feeding tube, mechanical ventilation, and recent history of
      pneumonia. Fluoroquinolone-resistant (57% vs 34%, 16%; p < 0.0001) and multidrug
      resistant (36% vs 26%, 7%; p = 0.0045) strains were more likely to cause
      pneumonia than bronchitis or colonization, respectively. Analysis of host and
      microbial factors in a multivariate regression model yielded the combined traits
      of fluoroquinolone resistance and gene encoding the type III secretion system
      ExoU effector in P. aeruginosa as the single most significant predictor of
      pneumonia development. CONCLUSIONS: These results suggest that fluoroquinolone
      resistant phenotype in a type III secretion system exoU strain background
      contributes toward the pathogenesis of P. aeruginosa in pneumonia.

PMID- 23963123
TI  - Role of diabetes in the development of acute respiratory distress syndrome.
AB  - OBJECTIVES: Diabetes has been associated with decreased development of acute
      respiratory distress syndrome in some, but not all, previous studies. Therefore,
      we examined the relationship between diabetes and development of acute
      respiratory distress syndrome and whether this association was modified by type
      of diabetes, etiology of acute respiratory distress syndrome, diabetes
      medications, or other potential confounders. DESIGN: Observational prospective
      multicenter study. SETTING: Four adult ICUs at two tertiary academic medical
      centers. PATIENTS: Three thousand eight hundred sixty critically ill patients at
      risk for acute respiratory distress syndrome from sepsis, pneumonia, trauma,
      aspiration, or massive transfusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Diabetes history was present in 25.8% of patients. Diabetes was
      associated with lower rates of developing acute respiratory distress syndrome on
      univariate (odds ratio, 0.79; 95% CI, 0.66-0.94) and multivariate analysis
      (adjusted odds ratio, 0.76; 95% CI, 0.61-0.95). After including diabetes
      medications into the model, diabetes remained protective (adjusted odds ratio,
      0.75; 95% CI, 0.59-0.94). Diabetes was associated with decreased development of
      acute respiratory distress syndrome both in the subgroup of patients with sepsis
      (adjusted odds ratio, 0.77; 95% CI, 0.61-0.97) and patients with noninfectious
      etiologies (adjusted odds ratio, 0.30; 95% CI, 0.10-0.90). The protective effect
      of diabetes on acute respiratory distress syndrome development is not clearly
      restricted to either type 1 (adjusted odds ratio, 0.50; 95% CI, 0.26-0.99; p =
      0.046) or type 2 (adjusted odds ratio, 0.77; 95% CI, 0.60-1.00; p = 0.050)
      diabetes. Among patients in whom acute respiratory distress syndrome developed,
      diabetes was not associated with 60-day mortality on univariate (odds ratio,
      1.11; 95% CI, 0.80-1.52) or multivariate analysis (adjusted odds ratio, 0.81; 95%
      CI, 0.56-1.18). CONCLUSIONS: Diabetes is associated with a lower rate of acute
      respiratory distress syndrome development, and this relationship remained after
      adjusting for clinical differences between diabetics and nondiabetics, such as
      obesity, acute hyperglycemia, and diabetes-associated medications. In addition,
      this association was present for type 1 and 2 diabetics and in all subgroups of
      at-risk patients.

PMID- 23963125
TI  - Preliminary report on cardiac dysfunction after isolated traumatic brain injury.
AB  - OBJECTIVE: The aim of this study was to examine cardiac dysfunction during the
      first 2 weeks after isolated traumatic brain injury and its association with in
      hospital mortality. DESIGN: Retrospective. SETTING: Level 1 regional trauma
      center. PATIENTS: Adult patients with severe traumatic brain injury. METHODS:
      After institutional review board approval, data from adult patients with isolated
      traumatic brain injury who underwent echocardiography during the first 2 weeks
      after traumatic brain injury between 2003 and 2010 were examined. Patients with
      preexisting cardiac disease were excluded. Clinical characteristics and
      echocardiogram reports were abstracted. Cardiac dysfunction was defined as left
      ventricular ejection fraction less than 50% or presence of regional wall motion
      abnormality. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We examined data
      from 139 patients with isolated traumatic brain injury who underwent
      echocardiographic evaluation. Patients were 58 +/- 20 years old, 66% were male
      patients, and 62.6% had subdural hematoma; admission Glasgow Coma Scale score was
      3 +/- 1 (3-15) and head Abbreviated Injury Scale was 4 +/- 1 (2-5). Of this
      cohort, 22.3% had abnormal echocardiogram: reduced left ventricular ejection
      fraction was documented in 12% (left ventricular ejection fraction, 43% +/- 8%)
      and 17.5% of patients had a regional wall motion abnormality. Hospital day 1 was
      the most common day of echocardiographic exam. Abnormal echocardiogram was
      independently associated with all cause in-hospital mortality (9.6 [2.3-40.2]; p
      = 0.002). CONCLUSIONS: Cardiac dysfunction in the setting of isolated traumatic
      brain injury occurs and is associated with increased in-hospital mortality. This
      finding raises the question as to whether there are uncharted opportunities for a
      more timely recognition of cardiac dysfunction and subsequent optimization of the
      hemodynamic management of these patients.

PMID- 23963126
TI  - The effects of critical illness on intestinal glucose sensing, transporters, and
      absorption.
AB  - OBJECTIVES: Providing effective enteral nutrition is important during critical
      illness. In health, glucose is absorbed from the small intestine via sodium
      dependent glucose transporter-1 and glucose transporter-2, which may both be
      regulated by intestinal sweet taste receptors. We evaluated the effect of
      critical illness on glucose absorption and expression of intestinal sodium
      dependent glucose transporter-1, glucose transporter-2, and sweet taste receptors
      in humans and mice. DESIGN: Prospective observational study in humans and mice.
      SETTING: ICU and university-affiliated research laboratory. SUBJECTS: Human
      subjects were 12 critically ill patients and 12 healthy controls. In the
      laboratory 16-week-old mice were studied. INTERVENTIONS: Human subjects underwent
      endoscopy. Glucose (30 g) and 3-O-methylglucose (3 g), used to estimate glucose
      absorption, were infused intraduodenally over 30 minutes. Duodenal mucosa was
      biopsied before and after infusion. Mice were randomized to cecal ligation and
      puncture to model critical illness (n = 16) or sham laparotomy (control) (n = 8).
      At day 5, mice received glucose (100 mg) and 3-O-methylglucose (10 mg) infused
      intraduodenally prior to mucosal tissue collection. MEASUREMENTS AND MAIN
      RESULTS: Quantitative polymerase chain reaction was performed to measure absolute
      (human) and relative levels of sodium-dependent glucose transporter-1, glucose
      transporter-2, and taste receptor type 1 member 2 (T1R2) transcripts. Blood
      samples were assayed for 3-O-methylglucose to estimate glucose absorption.
      Glucose absorption was three-fold lower in critically ill humans than in controls
      (p = 0.002) and reduced by a similar proportion in cecal ligation and puncture
      mice (p = 0.004). In critically ill patients, duodenal levels of sodium-dependent
      glucose transporter-1, glucose transporter-2, and T1R2 transcript were reduced
      49% (p < 0.001), 50% (p = 0.009), and 85% (p = 0.007), whereas in the jejunum of
      cecal ligation and puncture mice sodium-dependent glucose transporter-1, glucose
      transporter-2, and T1R2 transcripts were reduced by 55% (p < 0.001), 50% (p =
      0.002), and 69% (p = 0.004). CONCLUSIONS: Critical illness is characterized by
      markedly diminished glucose absorption, associated with reduced intestinal
      expression of glucose transporters (sodium-dependent glucose transporter-1 and
      glucose transporter-2) and sweet taste receptor transcripts. These changes are
      paralleled in cecal ligation and puncture mice.

PMID- 23963127
TI  - Profile of the risk of death after septic shock in the present era: an
      epidemiologic study.
AB  - OBJECTIVES: To investigate mortality of ICU patients over a 3-month period after
      an initial episode of septic shock and to identify factors associated with
      mortality. DESIGN: Prospective multicenter observational cohort study. SETTING:
      Fourteen ICUs from 10 French nonacademic and university teaching hospitals.
      PATIENTS: All consecutive adult patients with septic shock admitted between
      October 2009 and September 2011 were eligible. INTERVENTION: None. MEASUREMENTS
      AND MAIN RESULTS: Multivariable analyses were performed using a Cox proportional
      hazard model and a flexible extension of the Cox model. In total, 1,495 of 10,941
      patients (13.7%) had septic shock and 1,488 patients (99.5%) were included.
      Median age was 68 years (range, 58-78 yr). The majority of admissions (84%) were
      medical. Median (interquartile range) Simplified Acute Physiological Score II and
      Sequential Organ Failure Assessment were, respectively, 56 (45-70) and 11 (9-14).
      ICU and hospital mortality were, respectively, 39.4% and 48.6%. At 3 months, 776
      patients (52.2%) had died. Factors significantly associated with increased risk
      of death in the multivariable Cox model were older age, male sex, comorbidities
      (immune deficiency, cirrhosis), Knaus C/D score, and high Sequential Organ
      Failure Assessment score. Flexible analyses indicated that the impact of
      Sequential Organ Failure Assessment score was greatest early after septic shock,
      while the onset of the effect of age, nosocomial infection, and cirrhosis was
      later. CONCLUSIONS: This is the most recent large-scale epidemiological study to
      investigate medium-term mortality in nonselected patients hospitalized in the ICU
      for septic shock. Advances in early management have improved survival at the
      initial phase, but risk of death persists in the medium term. Flexible modeling
      techniques yield insights into the profile of the risk of death in the first 3
      months.

PMID- 23963128
TI  - Effects of clinical supervision on resident learning and patient care during
      simulated ICU scenarios.
AB  - OBJECTIVES: Closer supervision of residents' clinical activities has been
      promoted to improve patient safety, but may additionally affect resident
      participation in patient care and learning. The objective of this study was to
      determine the effects of closer supervision on patient care, resident
      participation, and the development of resident ability to care independently for
      critically ill patients during simulated scenarios. DESIGN: This quantitative
      study represents a component of a larger mixed-methods study. Residents were
      randomized to one of three levels of supervision, defined by the physical
      proximity of the supervisor (distant, immediately available, and direct). Each
      resident completed a simulation scenario under the supervision of a critical care
      fellow, immediately followed by a modified scenario of similar content without
      supervision. SETTING: The simulation center of a tertiary, university-affiliated
      academic center in a large urban city. SUBJECTS: Fifty-three residents completing
      a critical care rotation and 24 critical care fellows were recruited between
      April 2009 and June 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      During the supervised scenarios, lower team performance checklist scores were
      obtained for distant supervision compared with immediately available and direct
      supervision (mean [SD], direct: 72% [12%] vs immediately available: 77% [10%] vs
      distant: 61% [11%]; p = 0.0013). The percentage of checklist items completed by
      the residents themselves was significantly lower during direct supervision
      (median [interquartile range], direct: 40% [21%] vs immediately available: 58%
      [16%] vs distant: 55% [11%]; p = 0.005). During unsupervised scenarios, no
      significant differences were found on the outcome measures. CONCLUSIONS: Care
      delivered in the presence of senior supervising physicians was more comprehensive
      than care delivered without access to a bedside supervisor, but was associated
      with lower resident participation. However, subsequent resident performance
      during unsupervised scenarios was not adversely affected. Direct supervision of
      residents leads to improved care process and does not diminish the subsequent
      ability of residents to function independently.

PMID- 23963129
TI  - Synergistic deleterious effect of hypoxemia and hypovolemia on microcirculation
      in intestinal villi*.
AB  - OBJECTIVE: To investigate the effect of hypoxemia, hemorrhagic shock, and the
      association of both of these on intestinal microcirculation (microcirculatory
      perfusion and leukocytes-endothelium interactions in postcapillary venules), as
      it can be encountered in hemorrhagic shock following trauma. DESIGN: Prospective
      controlled experimental study. SETTING: University research laboratory. SUBJECTS:
      Forty-eight anesthetized and mechanically ventilated Balb/c mice. INTERVENTION:
      Mice were randomly assigned to hypoxemia group in which we decreased inspired
      oxygen fraction during 60 minutes to reach a PaO2 of 40 mm Hg, hemorrhagic shock
      group in which animals were exsanguinated to a mean arterial pressure level of 40
      mm Hg during 30 minutes, hypoxemia-hemorrhagic shock group in which PaO2 was
      decreased to 40 mm Hg during 60 minutes with exsanguination from the 30th to the
      60th minute to a mean arterial pressure level of 40 mm Hg; or control group.
      MEASUREMENTS AND MAIN RESULTS: Hypoxemia decreased RBCs velocity in intestinal
      villi but did not alter the fraction of perfused villi. Hypoxemia also triggered
      leukocytes adhesion to the venular endothelium. Hemorrhagic shock not only
      decreased RBCs velocity in villi but also slightly altered the fraction of
      perfused villi (94% +/- 2% in hemorrhagic shock group vs 100% +/- 0% in control
      group, p < 0.005). Furthermore, hemorrhagic shock triggered leukocytes adhesion
      to the venular endothelium to the same extent as hypoxemia. When hypoxemia was
      associated to hemorrhagic shock, it decreased villous RBCs velocity in an
      additive manner and the fraction of perfused villi dropped in a synergistic
      manner (69% +/- 3% in hypoxemia-hemorrhagic shock group vs 94 +/- 2 in
      hemorrhagic shock group, p < 0.005). The association of hypoxemia and hemorrhagic
      shock did not further amplify leukocytes adhesion to intestinal venules compared
      with either hypoxemia or hemorrhagic shock alone. CONCLUSIONS: During hemorrhagic
      shock, the occurrence of hypoxemia considerably alters villous intestinal
      perfusion as it decreases the fraction of perfused villi in a synergistic manner,
      thereby increasing the risk of villous ischemia. The association of hypoxemia and
      hemorrhagic shock did not amplify leukocytes adhesion to the endothelium further
      than either hemorrhagic shock or hypoxemia alone did. As hypoxemia frequently
      occurs simultaneously with hemorrhagic shock in traumatic conditions, it can
      worsen gut ischemia leading to the exacerbation of multiple organ failure
      syndrome.

PMID- 23963130
TI  - Mild hypothermia attenuates circulatory and pulmonary dysfunction during
      experimental endotoxemia.
AB  - OBJECTIVE: We tested whether mild hypothermia impacts on circulatory and
      respiratory dysfunction during experimental endotoxemia. DESIGN: Randomized
      controlled prospective experimental study. SETTING: Large animal facility,
      Medical University of Graz, Austria. SUBJECTS: Thirteen anesthetized and
      mechanically ventilated pigs. INTERVENTIONS: Lipopolysaccharide was administered
      for 4 hours. With the beginning of lipopolysaccharide infusion, animals were
      assigned to either normothermia (38 degrees C, n = 7) or mild hypothermia (33
      degrees C, n = 6, intravascular cooling) and followed for 8 hours in total.
      MEASUREMENTS AND MAIN RESULTS: At the end of the protocol, cardiac output was
      lower in mild hypothermia than in normothermia (4.5 +/- 0.4 L/min vs 6.6 +/- 0.4
      L/min, p < 0.05), but systemic vascular resistance (885 +/- 77 dyn.s/cm vs 531 +/
      29 dyn.s/cm, p < 0.05) and (Equation is included in full-text article.)(77% +/-
      6% vs 54% +/- 3%, p < 0.05) were higher. Indices of left ventricular
      contractility in vivo were not different between groups. The high-frequency band
      in spectral analysis of heart rate variability indicated a better preserved vagal
      autonomic modulation of sinuatrial node activity in mild hypothermia versus
      normothermia (87 +/- 5 vs 47 +/- 5, normalized units, p < 0.05). Plasma
      norepinephrine levels were elevated compared with baseline in normothermia (2.13
      +/- 0.27 log pg/mL vs 0.27 +/- 0.17 log pg/mL, p < 0.05) but not in mild
      hypothermia (1.02 +/- 0.31 vs 0.55 +/- 0.26, p = not significant). At 38 degrees
      C in vitro, left ventricular muscle strips isolated from the mild hypothermia
      group had a higher force response to isoproterenol. SaO2 (100% +/- 0% vs 92% +/-
      3%, p < 0.05) and the oxygenation index (PO2/FIO2, 386 +/- 52 mm Hg vs 132 +/- 32
      mm Hg, p < 0.05) were substantially higher in mild hypothermia versus
      normothermia. Plasma cytokine levels were not consistently different between
      groups (interleukin 10) or higher (tumor necrosis factor-alpha and interleukin 6
      and 8) during mild hypothermia versus normothermia. CONCLUSION: The induction of
      mild hypothermia attenuates cardiac and respiratory dysfunction and counteracts
      sympathetic activation during experimental endotoxemia. This was not associated
      with lower plasma cytokine levels, indicating a reduction of cytokine
      responsiveness by mild hypothermia.

PMID- 23963131
TI  - Clonidine and dexmedetomidine increase the pressor response to norepinephrine in
      experimental sepsis: a pilot study.
AB  - OBJECTIVE: During septic shock, vasopressors are a cornerstone of therapy. In
      septic shock, very high doses of vasopressors sometimes have to be used due to
      vascular desensitization, the mechanisms of which are poorly understood. This
      study assesses whether alpha-2 agonists increase pressor responsiveness following
      lipopolysaccharide administration. DESIGN: Parallel groups of animals (n = 7 per
      group) subjected to pharmacologic interventions. SETTING: Physiology laboratory.
      SUBJECTS: Rats. INTERVENTIONS: In anesthetized rats, the pressor responses to
      increasing doses of norepinephrine (norepinephrine-systolic pressure curve) were
      assessed during a baseline period, after injection of saline or
      lipopolysaccharide, and after subsequent injection of saline, dexmedetomidine
      (100 MUg/kg IV), or clonidine (200 MUg/kg IV). MEASUREMENTS AND MAIN RESULTS:
      Differences in the slopes of the norepinephrine-pressure curves were assessed
      across drug treatments and intervals. The pressor dose of norepinephrine
      necessary to increase systolic pressure by 33 and 100 mm Hg (pressor dose 33 and
      pressor dose 100) was determined. Pressor responsiveness to norepinephrine
      decreased slightly over time in the saline-saline group (saline 1 or 2 vs
      baseline: mean decrease of the slope, 2 mm Hg/MUg/kg norepinephrine; p < 0.05),
      whereas there was a large decrease after lipopolysaccharide (lipopolysaccharide
      vs baseline: mean decrease of the slope, 7.2; p < 0.001). Clonidine alone had no
      effect, but when administered following lipopolysaccharide, it caused a striking
      increase in pressor responsiveness (mean slope after lipopolysaccharide, 10.7
      [95% CI, 9.9-11.6]; after clonidine, 17.5 [95% CI, 16.7-18.4]). Similarly,
      dexmedetomidine administered after lipopolysaccharide caused a large increase in
      pressor responsiveness above lipopolysaccharide values. Accordingly the pressor
      dose 33 and pressor dose 100 values were lowered following lipopolysaccharide and
      restored by alpha-2 agonists. CONCLUSIONS: The pressor response to norepinephrine
      was reduced following lipopolysaccharide and increased to baseline levels
      following alpha-2 agonists.

PMID- 23963132
TI  - Repeated derecruitments accentuate lung injury during mechanical ventilation.
AB  - OBJECTIVES: The aim of our study was to assess whether repeated derecruitments
      induced by the repetitive withdrawal of high positive end-expiratory pressure
      could induce lung injury in a swine model. DESIGN: Prospective, randomized,
      experimental animal study. SETTING: University laboratory. SUBJECTS: Specific
      pathogen-free pigs (Choong-Ang Laboratory Animals, Seoul, Korea) weighing around
      30 kg. INTERVENTIONS: After lung injury was induced by repeated saline lavage,
      pigs were ventilated in pressure-limited mode with the highest possible positive
      end-expiratory pressure with a tidal volume of 8 mL/kg and maximum inspiratory
      pressure of 30 cm H2O. With this initial ventilator setting, the control group (n
      = 5) received ventilation without derecruitments for 4 hours, and in the
      derecruitment group (n = 5), derecruitments were repeatedly induced by
      intentional disconnection of the ventilatory circuit for 30 seconds every 5
      minutes for 4 hours. MEASUREMENTS AND MAIN RESULTS: After the initial increase in
      positive end-expiratory pressure, the PaO2 increased to greater than 450 mm Hg in
      both groups. The PaO2 remained at greater than 450 mm Hg in the control group
      persistently, but in the derecruitment group, PaO2 significantly decreased to
      427.7 mm Hg (adjusted p = 0.03) after 2 hours and remained significant for the
      rest of the study. PaCO2, oxygenation index, and alveolar-arterial oxygen
      gradient also significantly increased after 2 hours compared with the control
      group. However, the variables of respiratory mechanics except for minute volume
      at 2-hour point showed no difference between the two groups for the duration of
      the study. Histologically, significant bronchiolar injury was observed in the
      dependent portion of the derecruitment group compared with the controls (p =
      0.03), but not in the nondependent area of the lung. CONCLUSIONS: Repeated
      derecruitments exacerbated lung injury, particularly at the bronchiolar level in
      the dependent portion. Strategies to minimize this type of injury should be
      incorporated when designing optimal ventilator strategies in acute respiratory
      distress syndrome patients.

PMID- 23963133
TI  - Connection between cardiac vascular permeability, myocardial edema, and
      inflammation during sepsis: role of the alpha1AMP-activated protein kinase
      isoform.
AB  - OBJECTIVE: As adenosine monophosphate (AMP)-activated protein kinase both
      controls cytoskeleton organization in endothelial cells and exerts anti
      inflammatory effects, we here postulated that it could influence vascular
      permeability and inflammation, thereby counteracting cardiac wall edema during
      sepsis. DESIGN: Controlled animal study. SETTINGS: University research
      laboratory. SUBJECTS: C57BL/6J, alpha1AMPK, and alpha1AMPK mice. INTERVENTION:
      Sepsis was triggered in vivo using a sublethal injection of lipopolysaccharide
      (O55B5, 10 mg/kg), inducing systolic left ventricular dysfunction. Left
      ventricular function, edema, vascular permeability, and inflammation were
      assessed in vivo in both wild-type mice (alpha1AMPK) and alpha1AMP-activated
      protein kinase-deficient mice (alpha1AMPK). The 5-aminoimidazole-4-carboxamide
      riboside served to study the impact of AMP-activated protein kinase activation on
      vascular permeability in vivo. The integrity of endothelial cell monolayers was
      also examined in vitro after lipopolysaccharide challenge in the presence of
      aminoimidazole-4-carboxamide riboside and/or after alpha1AMP-activated protein
      kinase silencing. MEASUREMENTS AND MAIN RESULTS: alpha1AMP-activated protein
      kinase deficiency dramatically impaired tolerance to lipopolysaccharide
      challenge. Indeed, alpha1AMPK exhibited heightened cardiac vascular permeability
      after lipopolysaccharide challenge compared with alpha1AMPK. Consequently, an
      increase in left ventricular mass corresponding to exaggerated wall edema
      occurred in alpha1AMPK, without any further decrease in systolic function.
      Mechanistically, the lipopolysaccharide-induced alpha1AMPK cardiac phenotype
      could not be attributed to major changes in the systemic inflammatory response
      but was due to an increased disruption of interendothelial tight junctions.
      Accordingly, AMP-activated protein kinase activation by aminoimidazole-4
      carboxamide riboside counteracted lipopolysaccharide-induced hyperpermeability in
      wild-type mice in vivo as well as in endothelial cells in vitro. This effect was
      associated with a potent protection of zonula occludens-1 linear border pattern
      in endothelial cells. CONCLUSIONS: Our results demonstrate for the first time the
      involvement of a signaling pathway in the control of left ventricular wall edema
      during sepsis. AMP-activated protein kinase exerts a protective action through
      the preservation of interendothelial tight junctions. Interestingly, exaggerated
      left ventricular wall edema was not coupled with aggravated systolic dysfunction.
      However, it could contribute to diastolic dysfunction in patients with sepsis.

PMID- 23963134
TI  - Contribution of protein Z and protein Z-dependent protease inhibitor in
      generalized Shwartzman reaction.
AB  - OBJECTIVE: Sepsis, a leading cause of mortality in critically ill patients, is
      closely linked to the excessive activation of coagulation and inflammation.
      Protein Z, a cofactor for the protein Z-dependent protease inhibitor, enhances
      the inhibition of coagulation factor Xa, and protein Z-dependent protease
      inhibitor inhibits factor XIa in a protein Z-independent fashion. The functions
      of protein Z and protein Z-dependent protease inhibitor in the inflammatory and
      coagulant responses to septic illness have not been evaluated. DESIGN: For
      induction of generalized Shwartzman reaction, dorsal skinfold chamber-equipped
      mice were challenged twice with lipopolysaccharide (0.05 mg/kg on day -1 and 5
      mg/kg body weight 24 hr later). Time-matched control animals received equal
      volumes of saline. SETTING: University research laboratory. SUBJECTS,
      INTERVENTIONS, AND MEASUREMENTS: Using intravital fluorescence microscopy in
      protein Z-dependent protease inhibitor deficient (ZPI) and protein Z deficient
      (PZ) mice, as well as their wild-type littermates (ZPI, PZ), kinetics of
      light/dye-induced thrombus formation and microhemodynamics were assessed in
      randomly chosen venules. Plasma concentrations of chemokine (C-X-C motif) ligand
      1, interleukin-6, and interleukin-10 were measured. Liver and lung were harvested
      for quantitative analysis of leukocytic tissue infiltration and thrombus
      formation. MAIN RESULTS: After induction of generalized Shwartzman reaction, all
      mice showed significant impairment of microhemodynamics, including blood flow
      velocity, volumetric blood flow, and functional capillary density, as well as
      leukocytopenia and thrombocytopenia. Thrombus formation time was markedly
      prolonged after induction of generalized Shwartzman reaction in all mice, except
      of ZPI mice, which also had a significantly higher fraction of occluded vessels
      in liver sections. PZ mice developed the highest concentrations of interleukin-6
      and interleukin-10 in response to generalized Shwartzman reaction and showed
      greater leukocytic tissue infiltration than their wild-type littermates.
      CONCLUSIONS: In this murine model of generalized Shwartzman reaction, protein Z
      dependent protease inhibitor deficiency enhanced the thrombotic response to
      vascular injury, whereas protein Z deficiency increased inflammatory response.

PMID- 23963135
TI  - Volutrauma, but not atelectrauma, induces systemic cytokine production by lung
      marginated monocytes.
AB  - OBJECTIVES: Ventilator-induced lung injury has substantive impact on mortality of
      patients with acute respiratory distress syndrome. Although low tidal volume
      ventilation has been shown to reduce mortality, clinical benefits of open-lung
      strategy are controversial. In this study, we investigated the impact of two
      distinct forms of ventilator-induced lung injury, i.e., volutrauma and
      atelectrauma, on the progression of lung injury and inflammation, in particular
      alveolar and systemic cytokine production. DESIGN: Ex vivo study. SETTING:
      University research laboratory. SUBJECTS: C57BL/6 mice. INTERVENTIONS: Isolated,
      buffer-perfused lungs were allocated to one of three ventilatory protocols for 3
      hours: control group received low tidal volume (7 mL/kg) with positive end
      expiratory pressure (5 cm H2O) and regular sustained inflation; high-stretch
      group received high tidal volume (30-32 mL/kg) with positive end-expiratory
      pressure (3 cm H2O) and sustained inflation; and atelectasis group received the
      same tidal volume as control but neither positive end-expiratory pressure nor
      sustained inflation. MEASUREMENTS AND MAIN RESULTS: Both injurious ventilatory
      protocols developed comparable levels of physiological injury and pulmonary
      edema, measured by respiratory system mechanics and lavage fluid protein. High
      stretch induced marked increases in proinflammatory cytokines in perfusate and
      lung lavage fluid, compared to control. In contrast, atelectasis had no effect on
      perfusate cytokines compared to control but did induce some up-regulation of
      lavage cytokines. Depletion of monocytes marginated within the lung
      microvasculature, achieved by pretreating mice with i.v. liposome-encapsulated
      clodronate, significantly attenuated perfusate cytokine levels, especially tumor
      necrosis factor, in the high-stretch, but not atelectasis group. CONCLUSIONS:
      Volutrauma (high-stretch), but not atelectrauma (atelectasis), directly activates
      monocytes within the pulmonary vasculature, leading to cytokine release into
      systemic circulation. We postulate this as a potential explanation why open-lung
      strategy has limited mortality benefits in ventilated critically ill patients.

PMID- 23963136
TI  - P2X7 receptor antagonism inhibits p38 mitogen-activated protein kinase activation
      and ameliorates neuronal apoptosis after subarachnoid hemorrhage in rats.
AB  - OBJECTIVES: Brilliant blue G, a selective P2X7 receptor antagonist, exhibits
      neuroprotective properties. This study examined whether brilliant blue G
      treatment ameliorates early brain injury after experimental subarachnoid
      hemorrhage, specifically via inhibiting p38 mitogen-activated protein kinase
      related proapoptotic pathways. DESIGN: Controlled in vivo laboratory study.
      SETTING: Animal research laboratory. SUBJECTS: One hundred fifty-four adult male
      Sprague-Dawley rats weighing 280-320 g. INTERVENTIONS: Subarachnoid hemorrhage
      was induced in rats by endovascular perforation. Experiment 1 implemented sham
      operated rats (sham) and subarachnoid hemorrhage animals, which received vehicle
      (subarachnoid hemorrhage + vehicle), brilliant blue G (subarachnoid hemorrhage +
      brilliant blue G), or brilliant blue G plus 2'(3')-O-(4-Benzoylbenzoyl)adenosine
      5'-triphosphate (BzATP) (subarachnoid hemorrhage + brilliant blue G + BzATP). The
      animals were intraperitoneally treated with brilliant blue G (30 mg/kg) at 30
      minutes after subarachnoid hemorrhage. BzATP (50 MUg/rat), a P2X7 receptor
      agonist, was intracerebroventricularly administered. Experiment 2 implemented
      sham-operated rats (sham) and subarachnoid hemorrhage animals, which received
      vehicle (subarachnoid hemorrhage + vehicle), scramble small interfering RNA
      (subarachnoid hemorrhage + scramble small interfering RNA), or P2X7 receptor
      small interfering RNA (subarachnoid hemorrhage + P2X7 receptor small interfering
      RNA). Subarachnoid hemorrhage grading, neurobehavioral score, and brain edema
      were evaluated at 24 and 72 hours after surgery. The expression of phosphorylated
      p38 mitogen-activated protein kinase, phosphorylated extracellular signal
      regulated kinases, phosphorylated c-Jun N-terminal kinases, P2X7 receptor, Bcl-2,
      and cleaved caspase-3 in the left cerebral hemisphere were determined by Western
      blot. Neuronal apoptosis was examined by double immunofluorescence staining using
      P2X7 receptor, terminal deoxynucleotidyl transferase-mediated uridine 5'
      triphosphate-biotin nick end-labeling, and neuronal nuclei. MEASUREMENTS AND MAIN
      RESULTS: Brilliant blue G significantly improved neurobehavioral function and
      ameliorated brain water content at 24 and 72 hours after subarachnoid hemorrhage.
      BzATP reversed these treatment effects. Brilliant blue G attenuated neuronal
      apoptosis in the subcortex, which was associated with decreased expression of
      phosphorylated p38 mitogen-activated protein kinase and cleaved caspase-3 and an
      increased expression of Bcl-2 in the left cerebral hemisphere. The beneficial
      effects of P2X7 receptor small interfering RNA were also mediated by a p38
      mitogen-activated protein kinase pathway. CONCLUSIONS: Inhibition of P2X7
      receptor by brilliant blue G or P2X7 receptor small interfering RNA can prevent
      early brain injury via p38 mitogen-activated protein kinase after subarachnoid
      hemorrhage.

PMID- 23963137
TI  - Haemoptysis as a prognostic factor in lung adenocarcinoma after curative
      resection.
AB  - BACKGROUND: Haemoptysis is a common symptom of lung cancer. Its prognostic role
      and mechanisms are still poorly understood. METHODS: We retrospectively reviewed
      666 consecutive patients with primary lung adenocarcinoma who underwent complete
      resection. The prognostic value of haemoptysis with respect to overall survival
      (OS), disease-specific survival (DSS) and disease-free survival (DFS) was
      analysed. To further explore the possible mechanisms of haemoptysis, we evaluated
      vascular endothelial growth factor (VEGF) expression, tumour necrosis, vascular
      invasion and extratumoural microvessel density (MVD) in 112 randomly selected
      patients. RESULTS: Haemoptysis predicted poor OS, DSS and DFS in operable lung
      adenocarcinoma (all P<0.001). In addition, haemoptysis was associated with high
      white blood cell (WBC) count (P=0.032), high fibrinogen (Fib; P<0.001), high
      tumour greatest dimension (P<0.001), severe vascular invasion (P=0.002) and
      central tumour location (P<0.001). We obtained no statistically significant
      differences of VEGF expression, tumour necrosis and extratumoural MVD in
      haemoptysis and non-haemoptysis groups. CONCLUSION: Our study demonstrates that
      haemoptysis predicts poor OS, DSS and DFS in lung adenocarcinoma after curative
      resection. Vascular invasion rather than angiogenesis or tumour necrosis could be
      the most important mechanism of haemoptysis in lung adenocarcinoma.

PMID- 23963138
TI  - Evaluation of prognostic factors in liver-limited metastatic colorectal cancer: a
      preplanned analysis of the FIRE-1 trial.
AB  - BACKGROUND: Liver-limited disease (LLD) denotes a specific subgroup of metastatic
      colorectal cancer (mCRC) patients. PATIENTS AND METHODS: A total of 479 patients
      with unresectable mCRC from an irinotecan-based randomised phase III trial were
      evaluated. Patients with LLD and non-LLD and hepatic resection were
      differentiated. Based on baseline patient characteristic, prognostic factors for
      hepatic resection were evaluated. Furthermore, prognostic factors for median
      overall survival (OS) were estimated via Cox regression in LLD patients. RESULTS:
      Secondary liver resection was performed in 38 out of 479 patients (resection
      rate: 7.9%). Prognostic factors for hepatic resection were LLD, lactate
      dehydrogenase (LDH), node-negative primary, alkaline phosphatase (AP) and
      Karnofsky performance status (PS). Median OS was significantly increased after
      hepatic resection (48 months), whereas OS in LLD (17 months) and non-LLD (19
      months) was comparable in non-resected patients. With the inapplicability of
      Koehne's risk classification in LLD patients, a new score based on only the
      independent prognostic factors LDH and white blood cell (WBC) provided markedly
      improved information on the outcome. CONCLUSION: Patients undergoing hepatic
      resection showed favourable long-term survival, whereas non-resected LLD patients
      and non-LLD patients did not differ with regard to progression-free survival and
      OS. The LDH levels and WBC count were confirmed as prognostic factors and provide
      a useful and simple score for OS-related risk stratification also in LLD.

PMID- 23963139
TI  - Phase I/II trial of capecitabine and oxaliplatin in combination with bevacizumab
      and imatinib in patients with metastatic colorectal cancer: AIO KRK 0205.
AB  - BACKGROUND: Combined inhibition of platelet-derived growth factor receptor beta
      signalling and vascular endothelial growth factor promotes vascular normalisation
      in preclinical models and may lead to increased delivery of chemotherapy to
      tumour tissue. This phase I/II trial assessed the safety and efficacy of
      capecitabine plus oxaliplatin (XELOX) plus bevacizumab and imatinib in the first
      line treatment of patients with metastatic colorectal cancer. METHODS: Two dose
      levels (I/II) were defined: capecitabine 850/1000 mg m(-2) twice daily on days 1
      14; oxaliplatin 100/130 mg m(-2) on day 1; bevacizumab 7.5 mg kg(-1) on day 1;
      imatinib 300 mg day(-1) on days 1-21 every 21 days. The primary study endpoint
      was safety. The phase II secondary endpoint was 6-month progression-free survival
      (PFS). RESULTS: Dose level I was chosen for phase II testing because, even though
      further dose escalation was permitted by the protocol, gastrointestinal
      toxicities were considered to be clinically significant. A total of 49 patients
      were evaluated. The 6-month PFS rate was 76%, median PFS was 10.6 months and
      median overall survival was 23.2 months. Haematological toxicities were generally
      mild. Sensory neuropathy and diarrhoea were the most common grade 3 toxicities.
      CONCLUSION: The combination of XELOX with bevacizumab and imatinib is tolerable
      and has promising efficacy.

PMID- 23963140
TI  - Meta-analysis of agreement between MRI and pathologic breast tumour size after
      neoadjuvant chemotherapy.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has been proposed to guide breast
      cancer surgery by measuring residual tumour after neoadjuvant chemotherapy. This
      study-level meta-analysis examines MRI's agreement with pathology, compares MRI
      with alternative tests and investigates consistency between different measures of
      agreement. METHODS: A systematic literature search was undertaken. Mean
      differences (MDs) in tumour size between MRI or comparator tests and pathology
      were pooled by assuming a fixed effect. Limits of agreement (LOA) were estimated
      from a pooled variance by assuming equal variance of the differences across
      studies. RESULTS: Data were extracted from 19 studies (958 patients). The pooled
      MD between MRI and pathology from six studies was 0.1 cm (95% LOA: -4.2 to 4.4
      cm). Similar overestimation for MRI (MD: 0.1 cm) and ultrasound (US) (MD: 0.1 cm)
      was observed, with comparable LOA (two studies). Overestimation was lower for MRI
      (MD: 0.1 cm) than mammography (MD: 0.4 cm; two studies). Overestimation by MRI
      (MD: 0.1 cm) was smaller than underestimation by clinical examination (MD: -0.3
      cm). The LOA for mammography and clinical examination were wider than that for
      MRI. Percentage agreement between MRI and pathology was greater than that of
      comparator tests (six studies). The range of Pearson's/Spearman's correlations
      was wide (0.21-0.92; 16 studies). Inconsistencies between MDs, percentage
      agreement and correlations were common. CONCLUSION: Magnetic resonance imaging
      appears to slightly overestimate pathologic size, but measurement errors may be
      large enough to be clinically significant. Comparable performance by US was
      observed, but agreement with pathology was poorer for mammography and clinical
      examination. Percentage agreement can provide supplementary information to MDs
      and LOA, but Pearson's/Spearman's correlation does not provide evidence of
      agreement and should be avoided. Further comparisons of MRI and other tests using
      the recommended methods are warranted.

PMID- 23963141
TI  - A phase-1b study of everolimus plus paclitaxel in patients with small-cell lung
      cancer.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) pathway is dysregulated in
      small-cell lung cancer (SCLC) and everolimus is an oral mTOR inhibitor. METHODS:
      This phase-1b study assessed everolimus safety at the levels of 2.5, 5, or 10 mg
      once daily in combination with paclitaxel (175 mg m(-2)) once every 3 weeks in
      previously treated SCLC patients. The primary end point was to determine the
      maximum tolerated dose of everolimus. RESULTS: Among 21 enrolled patients, common
      drug-related adverse events were anaemia, neutropenia, thrombocytopenia, pain,
      hyperglycemia, and stomatitis. Out of 11 evaluable patients treated with
      everolimus at the level of 5 mg, 1 patient experienced dose-limiting toxicity
      (DLT) of grade 4 febrile neutropenia and grade 3 thrombocytopenia. The other two
      DLTs (grade 4 thrombocytopenia and grade 3 hyperglycemia) occurred in two out of
      three patients receiving everolimus 10 mg. The overall objective response rate
      was 28%. CONCLUSION: Everolimus showed an acceptable safety profile and
      preliminary antitumour activity at the dose of 5 mg once daily when combined with
      3-weekly paclitaxel 175 mg m(-2) in patients with SCLC.

PMID- 23963142
TI  - Celebrities and screening: a measurable impact on high-grade cervical neoplasia
      diagnosis from the 'Jade Goody effect' in the UK.
AB  - BACKGROUND: The celebrity Jade Goody's cervical cancer diagnosis was associated
      with increased UK cervical screening attendance. We wanted to establish if there
      was an increase in high-grade (HG) cervical neoplasia diagnoses, and if so, what
      the characteristics of the women with HG disease were. METHODS: We analysed
      prospective data on 3233 consecutive colposcopy referrals in North East London,
      UK, from 01 April 2005 to 30 June 2010. Characteristics and outcomes of pre- and
      post-Goody cohorts were compared. RESULTS: Goody's diagnosis was associated with
      an increased incidence of colposcopy referrals in all subsequent annual quarters
      (incidence rate ratio (IRR) 1.3-1.9, P<0.002-P<0.0005) and increased HG disease
      diagnoses in the fourth quarter 2008/2009 (IRR 1.3, P=0.05) and first quarter
      2009/2010 (IRR 1.3, P=0.07). We observed 1.90-fold (CI: 1.06-3.39), 2.06 (CI:
      1.13-3.76) and 2.13-fold (CI: 1.07-4.25) respective increases in the odds of HG
      disease women being screening-naive in the first and second quarter 2009/2010,
      and the first quarter 2010/2011 (P<0.04, P<0.02 and P<0.04, respectively). There
      was a 2.23-fold increase in the odds of screening-naive HG disease women being
      symptomatic post-Goody's diagnosis (P=0.023). The age distributions of the pre-
      and post-Goody cohorts did not differ in any study group. CONCLUSION: Continued
      publicity about celebrities' diagnoses might encourage screening in at-risk
      populations.

PMID- 23963143
TI  - Rationale and design of a UK database for a rare cancer type: the GEM Registry
      for gastrointestinal stromal tumours.
AB  - BACKGROUND: Despite advances in the management of and changes in clinical
      practice, little is known about the epidemiology, patterns of care and outcomes
      of gastrointestinal stromal tumour (GIST) patients in the UK. Patient registries
      are receiving increasing attention as they can provide important information on
      clinical practice and patient outcomes. The rationale and study design of the
      GIST Epidemiology and Management (GEM) Registry, which forms part of the routine
      clinical practice for GISTs in several UK centres, are described. METHODS: The
      GEM Registry is a secure web-based registry system designed around a Microsoft
      Access core using SQL interface. Demographic, surgical, histopathological and
      clinical data will be captured including treatment outcomes and survival. The
      registry was piloted in six centres and following further fine tuning of the data
      sets, ethical committee submission and approval was completed. RESULTS: The GEM
      National Registry is the first of its kind to be implemented in rare cancers in
      UK. The registry is being rolled out initially in selected centres with the aim
      to expand to other centres. The first publication reporting analyses of the
      central data set is anticipated for the summer of 2013. CONCLUSION: GEM Registry
      will enable us to obtain a clear picture of incidence/prevalence of GISTS in UK.
      Clinicians will be able to review the prognostic and predictive value of
      variables in a large prospective data set. The data can be used for planning the
      delivery and improving the quality of care. This information is likely to inform
      clinical practice and, in years to come, guide the development and implementation
      of clinical trials for novel tyrosine kinase inhibitors. The results will not
      only benefit the GIST community, but also serve as a basis for the study of other
      rare tumour types.

PMID- 23963144
TI  - Overestimated lead times in cancer screening has led to substantial
      underestimation of overdiagnosis.
AB  - BACKGROUND: Published lead time estimates in breast cancer screening vary from 1
      to 7 years and the percentages of overdiagnosis vary from 0 to 75%. The
      differences are usually explained as random variations. We study how much can be
      explained by using different definitions and methods. METHODS: We estimated the
      clinically relevant lead time based on the observed incidence reduction after
      attending the last screening round in the Norwegian mammography screening
      programme. We compared this estimate with estimates based on models that do not
      take overdiagnosis into account (model-based lead times), for varying levels of
      overdiagnosis. Finally, we calculated overdiagnosis adjusted for clinical and
      model-based lead times and compared results. RESULTS: Clinical lead time was
      about one year based on the reduction in incidence in women previously offered
      screening. When overdiagnosed tumours were included, the estimates increased to 4
      9 years, depending on the age at which screening begins and the level of
      overdiagnosis. Including all breast cancers detected in women long after the end
      of the screening programme dilutes the level of overdiagnosis by a factor of 2-3.
      CONCLUSION: When overdiagnosis is not taken into account, lead time is
      substantially overestimated. Overdiagnosis adjusted for model-based lead time is
      a function tending to zero, with no simple interpretation. Furthermore, the
      estimates are not in general comparable, because they depend on both the duration
      of screening and duration of follow-up. In contrast, overdiagnosis adjusted for
      clinically relevant tumours is a point estimate (and interpreted as percentage),
      which we find is the most reasonable method.

PMID- 23963145
TI  - Concurrent palliative chemoradiation leads to survival and quality of life
      benefits in poor prognosis stage III non-small-cell lung cancer: a randomised
      trial by the Norwegian Lung Cancer Study Group.
AB  - BACKGROUND: The palliative role of chemoradiation in the treatment of patients
      with locally advanced, inoperable non-small-cell lung cancer stage III and
      negative prognostic factors remains unresolved. METHODS: Patients not eligible
      for curative radiotherapy were randomised to receive either chemoradiation or
      chemotherapy alone. Four courses of intravenous carboplatin on day 1 and oral
      vinorelbin on days 1 and 8 were given with 3-week intervals. Patients in the
      chemoradiation arm also received radiotherapy with fractionation 42 Gy/15,
      starting at the second chemotherapy course. The primary end point was overall
      survival; secondary end points were health-related quality of life (HRQOL) and
      toxicity. RESULTS: Enrolment was terminated due to slow accrual after 191
      patients from 25 Norwegian hospitals were randomised. Median age was 67 years and
      21% had PS 2. In the chemotherapy versus the chemoradiation arm, the median
      overall survival was 9.7 and 12.6 months, respectively (P<0.01). One-year
      survival was 34.0% and 53.2% (P<0.01). Following a minor decline during
      treatment, HRQOL remained unchanged in the chemoradiation arm. The patients in
      the chemotherapy arm reported gradual deterioration during the subsequent months.
      In the chemoradiation arm, there were more hospital admissions related to side
      effects (P<0.05). CONCLUSION: Chemoradiation was superior to chemotherapy alone
      with respect to survival and HRQoL at the expense of more hospital admissions due
      to toxicity.

PMID- 23963146
TI  - Evaluating the role of fluorodeoxyglucose positron emission tomography-computed
      tomography in multi-disciplinary team recommendations for oesophago-gastric
      cancer.
AB  - BACKGROUND: National guidelines recommend that fluorodeoxyglucose positron
      emission tomography-computed tomography (PET-CT) is performed in all patients
      being considered for radical treatment of oesophageal or oesophago-gastric cancer
      without computerised tomography scan (CTS) evidence of metastasis. Guidance also
      mandates that all patients with cancer have treatment decisions made within the
      context of a multi-disciplinary team (MDT) meeting. Little is known, however,
      about the influence of PET-CT on decision making within MDTs. The aim of this
      study was to assess the role of PET-CT in oesophago-gastric cancer on MDT
      decision making. METHODS: A retrospective analysis of a prospectively held
      database of all patients with biopsy-proven oesophageal or oesophago-gastric
      cancer discussed by a specialist MDT was interrogated. Patients selected for
      radical treatment without CTS evidence of M1 disease were identified. The
      influence of PET-CT on MDT decision making was examined by establishing whether
      the PET-CT confirmed CTS findings of M0 disease (and did not change the patient
      staging pathway) or whether the PET-CT changed the pathway by showing unsuspected
      M1 disease, refuting CTS suspicious metastases, or identifying another lesion
      (needing further investigation). RESULTS: In 102 MDT meetings, 418 patients were
      discussed, of whom 240 were initially considered for radical treatment and 238
      undergoing PET-CT. The PET-CT confirmed CTS findings for 147 (61.8%) and changed
      MDT recommendations in 91 patients (38.2%) by (i) identifying M1 disease (n=43),
      (ii) refuting CTS suspicions of M1 disease (n=25), and (iii) identifying new
      lesions required for investigations (n=23). CONCLUSION: The addition of PET-CT to
      standard staging for oesophageal cancer led to changes in MDT recommendations in
      93 (38.2%) patients, improving patient selection for radical treatment. The
      validity of the proposed methods for evaluating PET-CT on MDT decision making
      requires more work in other centres and teams.

PMID- 23963149
TI  - Stromal fibrosis of the breast: outcome analysis.
AB  - BACKGROUND: Stromal fibrosis in the breast is a non-specific benign pathologic
      entity with wide spectrum of imaging finding. The false-negative rates (number of
      cancers missed) previously reported have limited value because short follow-up
      period and small number of populations. PURPOSE: To describe the mammographic and
      sonographic findings of stromal fibrosis of the breast diagnosed by imaging
      guided biopsy and to determine the false-negative rate at percutaneous biopsy.
      MATERIAL AND METHODS: Between January 2007 and December 2008, 3097 consecutive
      imaging-guided breast core biopsies were performed. Patients were included in our
      study if stromal fibrosis was the predominant pathologic finding. Patients who
      had received <2 years of follow-up were excluded. Mammographic and sonographic
      findings were reviewed. Follow-up imaging for >2 years and histologic data were
      reviewed to evaluate lesion stability. RESULTS: Stromal fibrosis was diagnosed in
      187 (6.0%) of 3097 imaging-guided biopsies among patients with >2 years of follow
      up (mean, 41.9 months). Among them, 91 (49%) of 187 lesions were not visible on
      mammography and calcifications were the most common findings, being identified in
      33 lesions (17.6%). The most common sonographic finding was an oval hypoechoic
      mass with a circumscribed margin. Forty-two lesions (22.5%) were excised. Four
      false-negative lesions (2.1%, 4/187) were identified; all false-negative lesions
      were diagnosed within 6 months because of imaging-pathology discordance (75%,
      3/4) or disease progression (25%, 1/4). CONCLUSION: Stromal fibrosis diagnosed by
      imaging-guided biopsy has a wide spectrum of imaging finding and can be managed
      safely with radiologic-pathologic correlation and subsequent short-term imaging
      follow-up.

PMID- 23963147
TI  - S-1 plus irinotecan and oxaliplatin for the first-line treatment of patients with
      metastatic colorectal cancer: a prospective phase II study and pharmacogenetic
      analysis.
AB  - BACKGROUND: S-1 is an oral fluoropyrimidine that mimics infusional 5
      fluorouracil. The aim of this phase II trial was to explore the clinical efficacy
      of the triplet regimen TIROX, which consists of S-1, irinotecan and oxaliplatin.
      METHODS: Forty-two chemo-naive patients with metastatic colorectal cancer (mCRC)
      were planned to be enrolled and be treated with irinotecan 150 mg m(-2) followed
      by oxaliplatin 85 mg m(-2) on day 1 and S-1 80 mg m(-2) per day from day 1 to 14
      every 3 weeks. Polymorphisms in the UGT1A1, UGT1A6, UGT1A7 and CYP2A6 genes were
      analysed. RESULTS: Between July 2007 and February 2008, 43 patients were
      enrolled. An objective response was noted in 29 patients (67.4%, 95% confidence
      interval: 53.4-81.4), of which 2 achieved durable complete responses. The median
      progression-free survival was 10.0 months and the median overall survival was
      19.2 months. Significant grade 3 or 4 adverse events were neutropenia (45.2%),
      febrile neutropenia (9.5%), diarrhoea (7.1%) and vomiting (9.5%). Increased
      gastrointestinal toxicities were associated with the presence of UGT1A6*2 or
      UGT1A7*3 and an improved tumour response was noted in those without variant
      alleles of CYP2A6 or UGT1A1*60. CONCLUSION: The combination of S-1, irinotecan
      and oxaliplatin showed favourable efficacy and tolerability in untreated patients
      with mCRC.

PMID- 23963148
TI  - Digital pattern recognition-based image analysis quantifies immune infiltrates in
      distinct tissue regions of colorectal cancer and identifies a metastatic
      phenotype.
AB  - BACKGROUND: Several studies in colorectal cancer (CRC) indicate a relationship
      between tumour immune infiltrates and clinical outcome. We tested the utility of
      a digital pattern recognition-based image analysis (DPRIA) system to segregate
      tissue regions and facilitate automated quantification of immune infiltrates in
      CRC. METHODS: Primary CRC with matched hepatic metastatic (n=7), primary CRC
      alone (n=18) and primary CRC with matched normal (n=40) tissue were analysed
      immunohistochemically. Genie pattern recognition software was used to segregate
      distinct tissue regions in combination with image analysis algorithms to quantify
      immune cells. RESULTS: Immune infiltrates were observed predominately at the
      invasive margin. Quantitative image analysis revealed a significant increase in
      the prevalence of Foxp3 (P<0.0001), CD8 (P<0.0001), CD68 (<0.0001) and CD31
      (<0.0001) positive cells in the stroma of primary and metastatic CRC, compared
      with tumour cell mass. A direct comparison between non-metastatic primary CRC
      (MET-) and primary CRC that resulted in metastasis (MET+) showed an
      immunosuppressive phenotype, with elevated Foxp3 (P<0.05) and reduced numbers of
      CD8 (P<0.05) cells in the stroma of MET+ compared with MET- samples. CONCLUSION:
      By combining immunohistochemistry with DPRIA, we demonstrate a potential
      metastatic phenotype in CRC. Our study accelerates wider acceptance and use of
      automated systems as an adjunct to traditional histopathological techniques.

PMID- 23963150
TI  - The prevalence of lymph node metastases in clinically N0 necks with oral cavity
      squamous cell carcinoma: is CT good enough for nodal staging?
AB  - BACKGROUND: Nodal metastases and extracapsular extension (ECE) are important
      prognostic indicators. However, the diagnostic accuracy of CT is still limited
      for patients with clinically N0 neck. PURPOSE: To determine the prevalence of
      lymph node (LN) metastases and ECE for oral cavity squamous cell carcinoma (SCC)
      patients with clinical and CT negative preoperative neck. MATERIAL AND METHODS:
      Thirty-two patients with N0 oral cavity SCC who underwent neck dissection were
      included in this retrospective analysis. The size of LN was measured on
      transverse CT images, and radiological size criterion was based upon a minimal
      axial diameter of 10 mm. Pathology was used as the standard reference. Imaging
      and histopathological correlation was done for 132 LN levels in the 32 patients.
      RESULTS: Fourteen of 32 patients (44%) had metastatic nodes and six patients had
      ECE. Among 132 LN levels, 22 levels (17%) had metastatic LNs (level I 5/37, level
      II 8/39, level III 7/35, level IV 2/18), and eight of 22 levels with metastases
      had ECE. Poorly differentiated histology was a predictive factor for LN
      metastases or ECE (poorly versus well and moderately differentiated SCC: P=0.07
      for LN metastases and P=0.08 for ECE, respectively). T-classification was also an
      important predictor for occult nodal metastases (2 of 10 patients in T1, 12 of 22
      patients in T2-4), although it did not reach statistical significance (P=0.11).
      CONCLUSION: Diagnostic accuracy of CT is limited among N0 oral cavity SCC
      patients. Neck dissection should be performed, particularly for patients with
      poorly differentiated SCC or higher T-classification.

PMID- 23963151
TI  - Utility of MRI and PET/CT after neoadjuvant chemotherapy in breast cancer
      patients: correlation with pathological response grading system based on tumor
      cellularity.
AB  - BACKGROUND: MRI and PET/CT are useful for assessing breast cancer patients after
      neoadjuvant chemotherapy (NAC). PURPOSE: To investigate the utility of MRI and
      PET/CT in the prediction of pathologic response to neoadjuvant chemotherapy using
      Miller-Payne grading system in patients with breast cancer. MATERIAL AND METHODS:
      From January 2008 to December 2010, 59 consecutive patients with pathologically
      proven breast cancer, who underwent neoadjuvant chemotherapy followed by surgery
      were retrospectively enrolled. The maximal diameter decrease rate and volume
      reduction rate by three-dimensional (3D) MRI and standardized uptake value (SUV)
      reduction rate by PET/CT were calculated and correlated with the Miller-Payne
      grading system using the Spearman rank correlation test. Patients with Miller
      Payne grades 1 or 2 were classified into the non-responder group and patients
      with grades 3, 4, and 5 were in the responder group. To differentiate between
      responders and non-responders, receiver-operating characteristic (ROC) analysis
      was performed. RESULTS: The volume reduction rate was 64.87 +/- 46.95, diameter
      decrease rate was 48.09 +/- 35.02, and SUV decrease rate was 62.10 +/- 32.17.
      Among three parameters, the volume reduction rate was most correlated with
      histopathologic grades of regression (rho = 0.755, P < .0001) followed by
      diameter decrease rate (rho = 0.660, P < 0.0001), and SUV decrease rate of
      primary breast mass (rho = 0.561, P = 0.0002). The area under the ROC curve (Az)
      value was largest in the volume reduction rate (Az = 0.9), followed by SUV
      decrease rate (Az = 0.875), and diameter decrease rate (Az = 0.849). The best cut
      offs for differentiating responders from non-responders in the ROC curve analysis
      were a 50% decrease in diameter, 68.9% decrease in volume, and 60.1% decrease in
      SUV after NAC. CONCLUSION: Volumetric measurement using 3D MRI combined with
      conventional diameter measurement may be more accurate to evaluate pathologic
      response after NAC.

PMID- 23963152
TI  - Effects of Mn-DPDP and manganese chloride on hemodynamics and glucose tolerance
      in anesthetized rats.
AB  - BACKGROUND: Previous studies have demonstrated that magnetic resonance imaging
      may be a method of choice to visualize transplanted pancreatic islets. However,
      contrast agents may interfere with microcirculation and affect graft function.
      PURPOSE: To evaluate the effects manganese-containing contrast media on regional
      blood flow and glucose tolerance. MATERIAL AND METHODS: Anesthetized rats were
      injected intravenously with MnCl2 (10 uM/kg body weight) or Mn-DPDP (TeslascanTM;
      5 uM/kg body weight). Blood flow measurements were made with a microsphere
      technique 10 min later. In separate animals vascular arteriolar reactivity in
      isolated, perfused islets was examined. Furthermore, an intraperitoneal glucose
      tolerance test was performed in separate rats. RESULTS: Glucose tolerance was
      unaffected by both agents. No changes in regional blood flow were seen after
      administration of Mn-DPDP, except for an increase in arterial liver blood flow.
      MnCl2 increased all blood flow values except that of the kidney. MnCl2, but not
      Mn-DPDP, caused a vasoconstriction in isolated rat islet arterioles but only at
      very high doses. CONCLUSION: Mn-DPDP administration does not affect glucose
      tolerance or regional blood flow, besides an increase in arterial hepatic blood
      flow, and may therefore be suitable for visualization of islets.

PMID- 23963153
TI  - Surface selective growth of ceria nanocrystals by CO absorption.
AB  - A significant morphology change from ceria nanoparticles to nanocubes was
      observed in ceria nanocrystals when CO molecules were introduced into the
      synthetic system, which is attributed to the surface selective growth driven by
      strong surface selective adsorption of CO onto the ceria surface. 

PMID- 23963154
TI  - Emergence of Porcine epidemic diarrhea virus in the United States: clinical
      signs, lesions, and viral genomic sequences.
AB  - During the 10 days commencing April 29, 2013, the Iowa State University
      Veterinary Diagnostic Laboratory received the first 4 of many submissions from
      swine farms experiencing explosive epidemics of diarrhea and vomiting affecting
      all ages, with 90-95% mortality in suckling pigs. Histology revealed severe
      atrophy of villi in all segments of the small intestines with occasional villus
      epithelial syncytial cells, but testing for rotaviruses and Transmissible
      gastroenteritis virus (Alphacoronavirus 1) were negative. Negative-staining
      electron microscopy of feces revealed coronavirus-like particles and a pan
      coronavirus polymerase chain reaction (PCR) designed to amplify a conserved
      region of the polymerase gene for all members in the family Coronaviridae
      produced expected 251-bp amplicons. Subsequent sequencing and analysis revealed
      99.6-100% identity among the PCR amplicons from the 4 farms and 97-99% identity
      to the corresponding portion of the polymerase gene of Porcine epidemic diarrhea
      virus (PEDV) strains, with the highest identity (99%) to strains from China in
      2012. Findings were corroborated at National Veterinary Services Laboratories
      using 2 nested S-gene and 1 nested N-gene PCR tests where the sequenced amplicons
      also had the highest identity with 2012 China strains. Whole genome sequence for
      the virus from 2 farms in 2 different states using next-generation sequencing
      technique was compared to PEDV sequences available in GenBank. The 2013 U.S. PEDV
      had 96.6-99.5% identity with all known PEDV strains and the highest identity
      (>99.0%) to some of the 2011-2012 Chinese strains. The nearly simultaneous
      outbreaks of disease, and high degree of homology (99.6-100%) between the PEDV
      strains from the 4 unrelated farms, suggests a common source of virus. 

PMID- 23963155
TI  - Incidence and clinical course of radionecrosis in children with brain tumors. A
      20-year longitudinal observational study.
AB  - Radionecrosis (RN) in children treated for brain tumors represents a potentially
      severe long-term complication. Its diagnosis is challenging, since magnetic
      resonance imaging (MRI) cannot clearly discriminate between RN and tumor
      recurrence. A retrospective single-center study was undertaken to describe the
      incidence and clinical course of RN in a cohort of 107 children treated with
      external radiotherapy (RT) for various brain tumors between 1992 and 2012. During
      a median follow-up of 4.6 years (range 0.29-20.1 years), RN was implied by
      suspicious MRI findings in in 5 children (4.7 %), 5-131 months after RT.
      Suspicion was confirmed histologically (1 patient) or substantiated by FDG
      positron-emission tomography (FDG-PET, 2 patients) or by FDG-PET and MR
      spectroscopy (1 patient). Before developing RN, all 5 patients had received
      cytotoxic chemotherapy in addition to RT. In addition to standard treatment
      protocols, 2 patients had received further chemotherapy for progression or
      relapse. Median radiation dose expressed as the biologically equivalent total
      dose applied in 2 Gy fractions (EQD2) was 51.7 Gy (range 51.0-60.0 Gy). At RN
      onset, 4 children presented with neurological symptoms. Treatment of RN included
      resection (n = 1), corticosteroids (n = 2) and a combination of corticosteroids,
      hyperbaric oxygen (HBO) and bevacizumab (n = 1). One patient with asymptomatic RN
      was not treated. Complete radiological regression of the lesions was observed in
      all patients. Clinical symptoms normalized in 3 patients, whereas 2 developed
      permanent severe neurological deficits. RN represents a severe long-term
      treatment complication in children with brain tumors. The spectrum of clinical
      presentation is wide; ranging from asymptomatic lesions to progressive
      neurological deterioration. FDG-PET and MR spectroscopy may be useful for
      distinguishing between RN and tumor recurrence. Treatment options in patients
      with symptomatic RN include conservative management (steroids, HBO, bevacizumab)
      and surgical resection. 

PMID- 23963156
TI  - [Prof. Dr. Wolfgang Hinkelbein conferred emeritus status].

PMID- 23963158
TI  - Metal array fabrication based on ultrasound-induced self-assembly of metalated
      dipeptides.
AB  - Pd- and Pt-bound bis-metalated peptides were synthesised by the condensation of
      Pd- or Pt-aldimine-complex-bound glutamic acids to afford the four possible metal
      isomers of bis-Pd and bis-Pt-homometalated dipeptides and PdPt- and PtPd
      heterometalated dipeptides without metal disproportionation. Ultrasound-induced
      self-assembly of these bis-metalated peptides proceeded effectively to afford
      supramolecular gels that displayed well-ordered metal arrays. The formation of
      parallel beta-sheet type aggregates through interpeptide amide-amide hydrogen
      bonding was confirmed by IR, scanning electron microscopy (SEM), and synchrotron
      X-ray diffraction analyses (WAXS and SAXS). The mechanism of the ultrasound
      induced self-assembly of the metalated dipeptides was elucidated via kinetic and
      association experiments by (1)H NMR, in which ultrasound-triggered dissociation
      of intramolecular hydrogen bonds between the chloride ligands of the Pd- and Pt
      complexes and amides initially occurred. This was followed by the formation of
      intermolecular amide-amide hydrogen bonds, which afforded the corresponding
      oligomeric peptide self-assembly as the nucleus for supramolecular aggregation.
      The observed first-order relationship of the gelation rate versus the sonication
      frequency suggested that the microcavitation generated under sonication
      conditions acted as a crucial trigger and provided a reaction field for efficient
      self-assembly. 

PMID- 23963159
TI  - Arrhythmia risk in long QT syndrome: beyond the disease-causative mutation.

PMID- 23963160
TI  - To replicate or not to replicate: the case of pharmacogenetic studies:
      Establishing validity of pharmacogenomic findings: from replication to
      triangulation.

PMID- 23963161
TI  - To replicate or not to replicate: the case of pharmacogenetic studies: Have
      pharmacogenomics failed, or do they just need larger-scale evidence and more
      replication?

PMID- 23963162
TI  - Identification of a growth factor that rejuvenates the heart.

PMID- 23963163
TI  - MicroRNA-34a: a new piece in the cardiac aging puzzle.

PMID- 23963164
TI  - Dexamethasone induces cross-linked actin networks in trabecular meshwork cells
      through noncanonical wnt signaling.
AB  - PURPOSE: Dexamethasone (DEX) regulates aqueous humor outflow by inducing a
      reorganization of the cytoskeleton to form cross-linked actin networks (CLANs) in
      trabecular meshwork (TM) cells. Rho-associated protein kinase (ROCK) has been
      demonstrated to have an important role in this process, but the upstream
      components leading to its activation remain elusive. The purpose of the study is
      to demonstrate that noncanonical Wnt signaling mediates the DEX-induced CLAN
      formation in TM cells. METHODS: The TM cells were treated with 100 nM DEX in low
      serum medium for over 7 days. The medium was changed every 3 days. The cells were
      harvested and subjected to molecular analysis for the expression of Wnt ligands.
      Stress fiber structures were revealed by Phalloidin staining. Lentivirus-based
      shRNA against noncanonical Wnt receptor (Ror2) was used to determine the role of
      noncanonical Wnt signaling in DEX-induced CLAN formation. RESULTS: The DEX
      induced stress fiber rearrangement in TM cells. A noncanonical Wnt ligand (Wnt5a)
      was upregulated by DEX as demonstrated by Wnt ligand degenerate PCR, real-time
      quantitative PCR (qRT-PCR), and Western blotting. Knocking-down Ror2, the
      receptor of noncanonical Wnt signaling, abolished the effects of DEX on the TM
      cells. CONCLUSIONS: Our data suggest that DEX induces the upregulation of
      noncanonical Wnt ligand Wnt5a. Recombinant WNT5a protein induces CLAN formation
      through the noncanonical Wnt receptor ROR2/RhoA/ROCK signaling axis. Given the
      similarities between DEX-induced ocular hypertension and primary open-angle
      glaucoma, our results provide a mechanism of action for applying ROCK inhibitor
      to treat primary open-angle glaucoma.

PMID- 23963166
TI  - Relationship between 24-hour mean ocular perfusion pressure fluctuation and rate
      of paracentral visual field progression in normal-tension glaucoma.
AB  - PURPOSE: To investigate the relationship between unstable mean ocular perfusion
      pressure (MOPP) and the rate of paracentral visual field (PVF) progression in
      patients with medically treated normal-tension glaucoma (NTG). METHODS: The data
      of 157 eyes of 122 patients with NTG who were followed for more than 6 years
      (mean follow-up, 8.7 years +/- 12.6 months) and had more than 5 reliable standard
      visual field (VF) tests were analyzed retrospectively. Groups in the highest,
      middle, and lowest tertiles of 24-hour MOPP fluctuation (HMF, MMF, and LMF,
      respectively) were compared in terms of rates of change of mean thresholds in the
      central 10 degrees  (PVF), 10 degrees  to 24 degrees , and global areas by using
      a linear mixed model. Clinical factors associated with rapid PVF progression were
      also investigated. RESULTS: The LMF and HMF groups did not differ significantly
      in the mean global rate of VF changes (-0.52 vs. -0.71 dB/y; P = 0.07). The HMF
      group had a significantly faster progression of VF defects in the central 10
      degrees  area than the LMF group (-1.02 vs. -0.54 dB/y; P < 0.001) but did not
      differ in terms of progression of VF defects in the peripheral 10 degrees  to 24
      degrees  area (-0.39 vs. -0.495 dB/y; P = 0.425). PVF progression was
      significantly associated with 24-hour MOPP fluctuation (beta = -0.31, P < 0.001)
      and VF damage severity at initial presentation (beta = 0.134, P = 0.011).
      CONCLUSIONS: Medically treated NTG eyes with greater 24-hour MOPP fluctuations
      (HMF) had faster PVF defect progression than eyes with stable 24-hour MOPP (LMF).
      Twenty-four hour MOPP fluctuation associated significantly with PVF progression
      velocity.

PMID- 23963165
TI  - Role of thrombospondin-1 in repair of penetrating corneal wounds.
AB  - PURPOSE: Thrombospondin-1 (THBS1) has been suggested as a corneal wound-healing
      modulator. Therefore, we compromised the integrity of the cornea to elucidate the
      role of THBS1. METHODS: Full-thickness penetrating corneal incisions (1.5 mm)
      were created in wild type (WT, 129S2/SvPas) and THBS1-deficient mice (Thbs1-/-),
      129S2/SvPas-Thbs1(tm1Hyn)/Thbs1(tm1Hyn)), and allowed to heal up to 1 month,
      while being monitored by slit-lamp and intravital corneal examinations. Corneas
      also were examined by transmission electron microscopy and indirect
      immunofluorescence. To determine how THBS1 was involved in the healing process,
      we examined THBS1 and alpha-smooth muscle actin (SMA), a marker of myofibroblasts
      and myoepithelial cells. RESULTS: In WT mice by 1 month, corneas appeared
      transparent with a thin scar, and endothelium and Descemet's membrane (DM) were
      restored. In contrast, Thbs1-/- corneas exhibited chronic edema and persistent
      opacity after wounding. The DM and endothelium were not restored, and wound
      contraction was impaired. The THBS1 was localized in epithelial cells at early
      stages of the healing process, and in the stroma and endothelial cells during
      later stages. The SMA-positive epithelial cells and myofibroblasts were observed
      within the healing area at day 4, peaked at day 14, and disappeared at day 30.
      The SMA-positive cells were reduced greatly in Thbs1-/- mice. CONCLUSIONS: In the
      current study, we demonstrated that corneal restoration is strikingly compromised
      by a penetrating incision in Thbs1-/- mice. The wound results in persistent edema
      and wound gaping. This appears to be the result of the lack of endothelial
      migration and DM restoration. In addition, myofibroblast formation is
      compromised, resulting in the lack of wound contraction.

PMID- 23963168
TI  - A mouse model of limbal stem cell deficiency induced by topical medication with
      the preservative benzalkonium chloride.
AB  - PURPOSE: To develop a mouse model of limbal stem cell deficiency (LSCD) by
      topical administration of benzalkonium chloride (BAC). METHODS: BAC solutions (0%
      0.5%) were applied to the mouse ocular surface for 4 weeks. Corneal
      neovascularization, inflammation, and epithelial status were observed under slit
      lamp microscope. The eyeball and ocular surface tissues were collected at 4 and
      12 weeks and labeled with a series of antibodies. Limbal structure was evaluated
      by light and transmission electron microscopy (TEM). Corneal impression cytology
      was performed at 12 weeks, and specimens were labeled with periodic acid Schiff
      (PAS) reagents. RESULTS: BAC (0.5%) four times per day for 28 days successfully
      induced the typical manifestations of LSCD, including corneal neovascularization,
      severe inflammation in the stroma, and diffuse epithelial defect (P < 0.001).
      Conjunctival epithelium markers K19 and K13 were positive on the corneal surface.
      Expression of the putative limbal stem cell markers P63 and ABCG2 was abolished
      in the limbal epithelium. beta-catenin was negative in the basal layer. TEM
      revealed the irregular basement membrane and the loss of stem cell-specific
      ultrastructure in the limbal basal epithelium. In the 0.5% BAC group, goblet
      cells could not be observed on day 28 but emerged after the cessation of BAC, and
      remained over the cornea after 8 weeks. K13-positive cells were still present
      over the cornea with the loss of K12. CONCLUSIONS: Topical administration of BAC
      at high concentration and frequency in mouse induces ocular surface changes
      resembling those of LSCD in humans, representing a novel model of LSCD.

PMID- 23963169
TI  - Use of pagers with an alarm escalation system to reduce cardiac monitor alarm
      signals.
AB  - Alarm fatigue desensitizes nurses to alarm signals and presents potential for
      patient harm. This project describes an innovative method of communicating
      cardiac monitor alarms to pagers using an alarm escalation algorithm. This
      innovation was tested on 2 surgical progressive care units over a 6-month period.
      There was a significant decrease in mean frequency and duration of high-priority
      monitor alarms and improvement in nurses' perception of alarm response time,
      using this method of alarm communication. 

PMID- 23963167
TI  - Investigation of known genetic risk factors for primary open angle glaucoma in
      two populations of African ancestry.
AB  - PURPOSE: Multiple genes have been associated with primary open angle glaucoma
      (POAG) in Caucasian populations. We now examine the association of these loci in
      populations of African ancestry, populations at particularly high risk for POAG.
      METHODS: We genotyped DNA samples from two populations: African American (1150
      cases and 999 controls) and those from Ghana, West Africa (483 cases and 593
      controls). Our analysis included 57 single nucleotide polymorphisms (SNPs) in
      five loci previously associated with POAG at the genome-wide level, including
      CDKN2B-AS1, TMCO1, CAV1/CAV2, chromosome 8q22 intergenic region, and SIX1/SIX6.
      We evaluated association in the full datasets, as well as subgroups with normal
      pressure glaucoma (NPG, maximum IOP <=21 mm Hg) and high pressure glaucoma (HPG,
      IOP >21 mm Hg). RESULTS: In African Americans, we identified an association of
      rs10120688 in the CDNK2B-AS1 region with POAG (P = 0.0020). Several other SNPs
      were nominally associated, but did not survive correction for multiple testing.
      In the subgroup analyses, significant associations were identified for rs10965245
      (P = 0.0005) in the CDKN2B-AS1 region with HPG and rs11849906 in the SIX1/SIX6
      region with NPG (P = 0.006). No significant association was identified with any
      loci in the Ghanaian samples. CONCLUSIONS: POAG genetic susceptibility alleles
      associated in Caucasians appear to play a greatly reduced role in populations of
      African ancestry. Thus, the major genetic components of POAG of African origin
      remain to be identified. This finding underscores the critical need to pursue
      large-scale genome-wide association studies in this understudied, yet
      disproportionately affected population.

PMID- 23963170
TI  - CD4(+) T-cell recovery after initiation of antiretroviral therapy in a resource
      limited setting: a prospective cohort analysis.
AB  - BACKGROUND: CD4(+) T-cell count recovery after antiretroviral therapy (ART)
      initiation is associated with improved health outcomes. It is unknown how the
      CD4(+) T-cell counts of African HIV patients recover following ART initiation.
      METHODS: We examined CD4(+) T-cell count recovery in a large cohort of HIV
      positive patients initiating ART in Uganda between 2004 and 2011. We categorized
      patients according to their CD4(+) T-cell count at ART initiation. All patients
      received CD4(+) T-cell count evaluations on a biannual basis. We used quantile
      regression to model the recovery of CD4(+) T-cells during ART. RESULTS: A total
      of 5,271 patients aged >=14 years at baseline were included. The median number of
      CD4(+) T-cell count measurements was 6 (IQR 4-8), and vital status at censoring
      was known in 97.2% of individuals. Most CD4(+) T-cell count recovery occurred
      within the first 12 months, with marginal increases beyond 18 months and
      stabilization after 5 years. The strongest predictor of CD4(+) T-cell count
      recovery was baseline CD4(+) T-cell count. After 5 years on treatment, the median
      CD4(+) T-cell count was 334 cells/mm(3) for patients initiating ART with <100
      cells/mm(3). Only those initiating ART with >200 cells/mm(3) reached a 5-year
      median >500 cells/mm(3). Adolescents had the most robust CD4(+) T-cell count
      recovery with a median increase after 12 months that was 109 cells/mm(3) greater
      than those initiating ART at age >=50 years. CONCLUSIONS: In individuals from a
      resource-limited setting, baseline CD4(+) T-cell count was highly predictive of
      the maximum CD4(+) T-cell count level achieved while on ART.

PMID- 23963171
TI  - Formulations for freeze-drying of bacteria and their influence on cell survival.
AB  - Cellular water can be removed to reversibly inactivate microorganisms to
      facilitate storage. One such method of removal is freeze-drying, which is
      considered a gentle dehydration method. To facilitate cell survival during
      drying, the cells are often formulated beforehand. The formulation forms a matrix
      that embeds the cells and protects them from various harmful stresses imposed on
      the cells during freezing and drying. We present here a general method to
      evaluate the survival rate of cells after freeze-drying and we illustrate it by
      comparing the results obtained with four different formulations: the disaccharide
      sucrose, the sucrose derived polymer Ficoll PM400, and the respective
      polysaccharides hydroxyethyl cellulose (HEC) and hydroxypropyl methyl cellulose
      (HPMC), on two strains of bacteria, P. putida KT2440 and A. chlorophenolicus A6.
      In this work we illustrate how to prepare formulations for freeze-drying and how
      to investigate the mechanisms of cell survival after rehydration by
      characterizing the formulation using of differential scanning calorimetry (DSC),
      surface tension measurements, X-ray analysis, and electron microscopy and
      relating those data to survival rates. The polymers were chosen to get a
      monomeric structure of the respective polysaccharide resembling sucrose to a
      varying degrees. Using this method setup we showed that polymers can support cell
      survival as effectively as disaccharides if certain physical properties of the
      formulation are controlled.

PMID- 23963173
TI  - Achiral guest-induced chiroptical changes of a planar-chiral pillar[5]arene
      containing one pi-conjugated unit.
AB  - A planar-chiral pillar[5]arene derivative containing one pi-conjugated unit was
      prepared. Chiroptical changes were observed upon addition of the achiral guest
      1,4-dicyanobutane. 

PMID- 23963174
TI  - Whole-genome sequencing of Trypanosoma brucei reveals introgression between
      subspecies that is associated with virulence.
AB  - Human African trypanosomiasis is caused by two subspecies of Trypanosoma brucei.
      Trypanosoma brucei rhodesiense is found in East Africa and frequently causes
      acute disease, while Trypanosoma brucei gambiense is found in West Africa and is
      associated with chronic disease. Samples taken from a single focus of a Ugandan
      outbreak of T. b. rhodesiense in the 1980s were associated with either chronic or
      acute disease. We sequenced the whole genomes of two of these isolates, which
      showed that they are genetically distinct from each other. Analysis of single
      nucleotide polymorphism markers in a panel of 31 Ugandan isolates plus 32
      controls revealed a mixture of East African and West African haplotypes, and some
      of these haplotypes were associated with the different virulence phenotypes. It
      has been shown recently that T. b. brucei and T. b. rhodesiense populations
      undergo genetic exchange in natural populations. Our analysis showed that these
      strains from the Ugandan epidemic were intermediate between the reference genome
      sequences of T. b. gambiense and T. b. brucei and contained haplotypes that were
      present in both subspecies. This suggests that the human-infective subspecies of
      T. brucei are not genetically isolated, and our data are consistent with genomic
      introgression between East African and West African T. b. brucei subspecies. This
      has implications for the control of the parasite, the spread of drug resistance,
      and understanding the variation in virulence and the emergence of human
      infectivity. IMPORTANCE: We present a genetic study of the acute form of
      "sleeping sickness" caused by the protozoan parasite Trypanosoma brucei
      rhodesiense from a single outbreak in Uganda. This represents an advance in our
      understanding of the relationship between the T. b. rhodesiense and Trypanosoma
      brucei gambiense subspecies that have previously been considered geographically
      distinct. Our data suggest that introgression of West African-derived T. brucei
      haplotypes may be associated with differences in disease presentation in the East
      African disease. These findings are not only of scientific interest but also
      important for parasite control, as they suggest that the human-infective T.
      brucei subspecies are not genetically isolated.

PMID- 23963176
TI  - A dysfunctional tricarboxylic acid cycle enhances fitness of Staphylococcus
      epidermidis during beta-lactam stress.
AB  - A recent controversial hypothesis suggested that the bactericidal action of
      antibiotics is due to the generation of endogenous reactive oxygen species (ROS),
      a process requiring the citric acid cycle (tricarboxylic acid [TCA] cycle). To
      test this hypothesis, we assessed the ability of oxacillin to induce ROS
      production and cell death in Staphylococcus epidermidis strain 1457 and an
      isogenic citric acid cycle mutant. Our results confirm a contributory role for
      TCA-dependent ROS in enhancing susceptibility of S. epidermidis toward beta
      lactam antibiotics and also revealed a propensity for clinical isolates to
      accumulate TCA cycle dysfunctions presumably as a way to tolerate these
      antibiotics. The increased protection from beta-lactam antibiotics could result
      from pleiotropic effects of a dysfunctional TCA cycle, including increased
      resistance to oxidative stress, reduced susceptibility to autolysis, and a more
      positively charged cell surface. IMPORTANCE: Staphylococcus epidermidis, a normal
      inhabitant of the human skin microflora, is the most common cause of indwelling
      medical device infections. In the present study, we analyzed 126 clinical S.
      epidermidis isolates and discovered that tricarboxylic acid (TCA) cycle
      dysfunctions are relatively common in the clinical environment. We determined
      that a dysfunctional TCA cycle enables S. epidermidis to resist oxidative stress
      and alter its cell surface properties, making it less susceptible to beta-lactam
      antibiotics.

PMID- 23963175
TI  - Transcriptional profiling of Staphylococcus aureus during growth in 2 M NaCl
      leads to clarification of physiological roles for Kdp and Ktr K+ uptake systems.
AB  - Staphylococcus aureus exhibits an unusually high level of osmotolerance and Na(+)
      tolerance, properties that support survival in various host niches and in
      preserved foods. The genetic basis of these traits is not well understood. We
      compared the transcriptional profiles of S. aureus grown in complex medium with
      and without 2 M NaCl. The stimulon for growth in high-osmolality media and Na(+)
      included genes involved in uptake of K(+), other compatible solutes, sialic acid,
      and sugars; capsule biosynthesis; and amino acid and central metabolism.
      Quantitative PCR analysis revealed that the loci responded differently from each
      other to high osmolality imposed by elevated NaCl versus sucrose. High-affinity
      K(+) uptake (kdp) genes and capsule biosynthesis (cap5) genes required the two
      component system KdpDE for full induction by osmotic stress, with kdpA induced
      more by NaCl and cap5B induced more by sucrose. Focusing on K(+) importers, we
      identified three S. aureus genes belonging to the lower-affinity Trk/Ktr family
      that encode two membrane proteins (KtrB and KtrD) and one accessory protein
      (KtrC). In the absence of osmotic stress, the ktr gene transcripts were much more
      abundant than the kdpA transcript. Disruption of S. aureus kdpA caused a growth
      defect under low-K(+) conditions, disruption of ktrC resulted in a significant
      defect in 2 M NaCl, and a DeltaktrC DeltakdpA double mutant exhibited both
      phenotypes. Protective effects of S. aureus Ktr transporters at elevated NaCl are
      consistent with previous indications that both Na(+) and osmolality challenges
      are mitigated by the maintenance of a high cytoplasmic K(+) concentration.
      IMPORTANCE: There is general agreement that the osmotolerance and Na(+) tolerance
      of Staphylococcus aureus are unusually high for a nonhalophile and support its
      capacity for human colonization, pathogenesis, and growth in food. Nonetheless,
      the molecular basis for these properties is not well defined. The genome-wide
      response of S. aureus to a high concentration, 2 M, of NaCl revealed the
      upregulation of expected genes, such as those for transporters of compatible
      solutes that are widely implicated in supporting osmotolerance. A high-affinity
      potassium uptake system, KdpFABC, was upregulated, although it generally plays a
      physiological role under very low K(+) conditions. At higher K(+) concentrations,
      a lower-affinity and more highly expressed type of K(+) transporter system, Ktr
      transporters, was shown to play a significant role in high Na(+) tolerance. This
      study illustrates the importance of the K(+) status of the cell for tolerance of
      Na(+) by S. aureus and underscores the importance of monovalent cation cycles in
      this pathogen.

PMID- 23963177
TI  - Interspecies interactions stimulate diversification of the Streptomyces
      coelicolor secreted metabolome.
AB  - Soils host diverse microbial communities that include filamentous actinobacteria
      (actinomycetes). These bacteria have been a rich source of useful metabolites,
      including antimicrobials, antifungals, anticancer agents, siderophores, and
      immunosuppressants. While humans have long exploited these compounds for
      therapeutic purposes, the role these natural products may play in mediating
      interactions between actinomycetes has been difficult to ascertain. As an initial
      step toward understanding these chemical interactions at a systems level, we
      employed the emerging techniques of nanospray desorption electrospray ionization
      (NanoDESI) and matrix-assisted laser desorption ionization-time of flight (MALDI
      TOF) imaging mass spectrometry to gain a global chemical view of the model
      bacterium Streptomyces coelicolor interacting with five other actinomycetes. In
      each interaction, the majority of secreted compounds associated with S.
      coelicolor colonies were unique, suggesting an idiosyncratic response from S.
      coelicolor. Spectral networking revealed a family of unknown compounds produced
      by S. coelicolor during several interactions. These compounds constitute an
      extended suite of at least 12 different desferrioxamines with acyl side chains of
      various lengths; their production was triggered by siderophores made by
      neighboring strains. Taken together, these results illustrate that chemical
      interactions between actinomycete bacteria exhibit high complexity and
      specificity and can drive differential secondary metabolite production.
      IMPORTANCE: Actinomycetes, filamentous actinobacteria from the soil, are the
      deepest natural source of useful medicinal compounds, including antibiotics,
      antifungals, and anticancer agents. There is great interest in developing new
      strategies that increase the diversity of metabolites secreted by actinomycetes
      in the laboratory. Here we used several metabolomic approaches to examine the
      chemicals made by these bacteria when grown in pairwise coculture. We found that
      these interspecies interactions stimulated production of numerous chemical
      compounds that were not made when they grew alone. Among these compounds were at
      least 12 different versions of a molecule called desferrioxamine, a siderophore
      used by the bacteria to gather iron. Many other compounds of unknown identity
      were also observed, and the pattern of compound production varied greatly among
      the interaction sets. These findings suggest that chemical interactions between
      actinomycetes are surprisingly complex and that coculture may be a promising
      strategy for finding new molecules from actinomycetes.

PMID- 23963178
TI  - Superantigens are critical for Staphylococcus aureus Infective endocarditis,
      sepsis, and acute kidney injury.
AB  - Infective endocarditis and kidney infections are serious complications of
      Staphylococcus aureus sepsis. We investigated the role of superantigens (SAgs) in
      the development of lethal sepsis, infective endocarditis, and kidney infections.
      SAgs cause toxic shock syndrome, but it is unclear if SAgs contribute to
      infective endocarditis and kidney infections secondary to sepsis. We show in the
      methicillin-resistant S. aureus strain MW2 that lethal sepsis, infective
      endocarditis, and kidney infections in rabbits are critically dependent on high
      level SAgs. In contrast, the isogenic strain lacking staphylococcal enterotoxin C
      (SEC), the major SAg in this strain, is attenuated in virulence, while
      complementation restores disease production. SAgs' role in infective endocarditis
      appears to be both superantigenicity and direct endothelial cell stimulation.
      Maintenance of elevated blood pressure by fluid therapy significantly protects
      from infective endocarditis, possibly through preventing bacterial accumulation
      on valves and increased SAg elimination. These data should facilitate better
      methods to manage these serious illnesses. IMPORTANCE: The Centers for Disease
      Control and Prevention reported in 2007 that Staphylococcus aureus is the most
      significant cause of serious infectious diseases in the United States (R. M.
      Klevens, M. A. Morrison, J. Nadle, S. Petit, K. Gershman, et al., JAMA 298:1763
      1771, 2007). Among these infections are sepsis, infective endocarditis, and acute
      kidney injury. Infective endocarditis occurs in 30 to 60% of patients with S.
      aureus bacteremia and carries a mortality rate of 40 to 50%. Over the past
      decades, infective endocarditis outcomes have not improved, and infection rates
      are steadily increasing (D. H. Bor, S. Woolhandler, R. Nardin, J. Brusch, D. U.
      Himmelstein, PLoS One 8:e60033, 2013). There is little understanding of the S.
      aureus virulence factors that are key for infective endocarditis development and
      kidney abscess formation. We demonstrate that superantigens are critical in the
      causation of all three infections. We show that their association results from
      both superantigenicity and direct toxic effects on endothelial cells, the latter
      likely contributing to delayed endothelium healing. Our studies contribute
      significantly to understanding the development of these illnesses and are
      expected to lead to development of important therapies to treat such illnesses.

PMID- 23963179
TI  - The Middle East respiratory syndrome--how worried should we be?
AB  - Ten years after the severe acute respiratory syndrome epidemic, a second
      coronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV), has
      been identified as the cause of a highly lethal pneumonia in patients in the
      Middle East and in travelers from this region. Over the past 9 months, since the
      virus was first isolated, much has been learned about the biology of the virus.
      It is now clear that MERS-CoV is transmissible from person to person, and its
      close relationship with several bat coronaviruses suggests that these animals may
      be the ultimate source of the infection. However, many key issues need to be
      addressed, including identification of the proximate, presumably zoonotic, source
      of the infection, the prevalence of the infection in human populations, details
      regarding clinical and pathological features of the human infection, the
      establishment of a small rodent model for the infection, and the virological and
      immune basis for the severe disease observed in most patients. Most importantly,
      we do not know whether a MERS-CoV epidemic is likely or not. Infection with the
      virus has so far resulted in only 91 cases and 46 deaths (as of 29 July 2013),
      but it is nonetheless setting off alarm bells among public health officials,
      including Margaret Chan, Director-General of the World Health Organization, who
      called MERS-CoV "a threat to the entire world." This article reviews some of the
      progress that has been made and discusses some of the questions that need to be
      answered.

PMID- 23963181
TI  - "But nature started it": examining Taubenberger and Morens' view on influenza A
      virus and dual-use research of concern.

PMID- 23963182
TI  - Load-dependent assembly of the bacterial flagellar motor.
AB  - It is becoming clear that the bacterial flagellar motor output is important not
      only for bacterial locomotion but also for mediating the transition from liquid
      to surface living. The output of the flagellar motor changes with the mechanical
      load placed on it by the external environment: at a higher load, the motor runs
      more slowly and produces higher torque. Here we show that the number of torque
      generating units bound to the flagellar motor also depends on the external
      mechanical load, with fewer stators at lower loads. Stalled motors contained at
      least as many stators as rotating motors at high load, indicating that rotation
      is unnecessary for stator binding. Mutant stators incapable of generating torque
      could not be detected around the motor. We speculate that a component of the
      bacterial flagellar motor senses external load and mediates the strength of
      stator binding to the rest of the motor. IMPORTANCE: The transition between
      liquid living and surface living is important in the life cycles of many
      bacteria. In this paper, we describe how the flagellar motor, used by bacteria
      for locomotion through liquid media and across solid surfaces, is capable of
      adjusting the number of bound stator units to better suit the external load
      conditions. By stalling motors using external magnetic fields, we also show that
      rotation is not required for maintenance of stators around the motor; instead,
      torque production is the essential factor for motor stability. These new results,
      in addition to previous data, lead us to hypothesize that the motor stators
      function as mechanosensors as well as functioning as torque-generating units.

PMID- 23963180
TI  - Emergence of epidemic multidrug-resistant Enterococcus faecium from animal and
      commensal strains.
AB  - Enterococcus faecium, natively a gut commensal organism, emerged as a leading
      cause of multidrug-resistant hospital-acquired infection in the 1980s. As the
      living record of its adaptation to changes in habitat, we sequenced the genomes
      of 51 strains, isolated from various ecological environments, to understand how
      E. faecium emerged as a leading hospital pathogen. Because of the scale and
      diversity of the sampled strains, we were able to resolve the lineage responsible
      for epidemic, multidrug-resistant human infection from other strains and to
      measure the evolutionary distances between groups. We found that the epidemic
      hospital-adapted lineage is rapidly evolving and emerged approximately 75 years
      ago, concomitant with the introduction of antibiotics, from a population that
      included the majority of animal strains, and not from human commensal lines. We
      further found that the lineage that included most strains of animal origin
      diverged from the main human commensal line approximately 3,000 years ago, a time
      that corresponds to increasing urbanization of humans, development of hygienic
      practices, and domestication of animals, which we speculate contributed to their
      ecological separation. Each bifurcation was accompanied by the acquisition of new
      metabolic capabilities and colonization traits on mobile elements and the loss of
      function and genome remodeling associated with mobile element insertion and
      movement. As a result, diversity within the species, in terms of sequence
      divergence as well as gene content, spans a range usually associated with
      speciation. IMPORTANCE: Enterococci, in particular vancomycin-resistant
      Enterococcus faecium, recently emerged as a leading cause of hospital-acquired
      infection worldwide. In this study, we examined genome sequence data to
      understand the bacterial adaptations that accompanied this transformation from
      microbes that existed for eons as members of host microbiota. We observed changes
      in the genomes that paralleled changes in human behavior. An initial bifurcation
      within the species appears to have occurred at a time that corresponds to the
      urbanization of humans and domestication of animals, and a more recent
      bifurcation parallels the introduction of antibiotics in medicine and
      agriculture. In response to the opportunity to fill niches associated with
      changes in human activity, a rapidly evolving lineage emerged, a lineage
      responsible for the vast majority of multidrug-resistant E. faecium infections.

PMID- 23963184
TI  - Reply to "'BUt nature started it': examining Taubenberger and Morens' view on
      influenza a virus and dual-use research of concern".

PMID- 23963183
TI  - Ferrous iron is a significant component of bioavailable iron in cystic fibrosis
      airways.
AB  - ABSTRACT Chronic, biofilm-like infections by the opportunistic pathogen
      Pseudomonas aeruginosa are a major cause of mortality in cystic fibrosis (CF)
      patients. While much is known about P. aeruginosa from laboratory studies, far
      less is understood about what it experiences in vivo. Iron is an important
      environmental parameter thought to play a central role in the development and
      maintenance of P. aeruginosa infections, for both anabolic and signaling
      purposes. Previous studies have focused on ferric iron [Fe(III)] as a target for
      antimicrobial therapies; however, here we show that ferrous iron [Fe(II)] is
      abundant in the CF lung (-39 uM on average for severely sick patients) and
      significantly correlates with disease severity (rho = -0.56, P = 0.004), whereas
      ferric iron does not (rho = -0.28, P = 0.179). Expression of the P. aeruginosa
      genes bqsRS, whose transcription is upregulated in response to Fe(II), was high
      in the majority of patients tested, suggesting that increased Fe(II) is
      bioavailable to the infectious bacterial population. Because limiting Fe(III)
      acquisition inhibits biofilm formation by P. aeruginosa in various oxic in vitro
      systems, we also tested whether interfering with Fe(II) acquisition would improve
      biofilm control under anoxic conditions; concurrent sequestration of both iron
      oxidation states resulted in a 58% reduction in biofilm accumulation and 28%
      increase in biofilm dissolution, a significant improvement over Fe(III) chelation
      treatment alone. This study demonstrates that the chemistry of infected host
      environments coevolves with the microbial community as infections progress, which
      should be considered in the design of effective treatment strategies at different
      stages of disease. IMPORTANCE: Iron is an important environmental parameter that
      helps pathogens thrive in sites of infection, including those of cystic fibrosis
      (CF) patients. Ferric iron chelation therapy has been proposed as a novel
      therapeutic strategy for CF lung infections, yet until now, the iron oxidation
      state has not been measured in the host. In studying mucus from the infected
      lungs of multiple CF patients from Europe and the United States, we found that
      ferric and ferrous iron change in concentration and relative proportion as
      infections progress; over time, ferrous iron comes to dominate the iron pool.
      This information is relevant to the design of novel CF therapeutics and, more
      broadly, to developing accurate models of chronic CF infections.

PMID- 23963185
TI  - Restoring institutional integrity in the wake of sexual boundary violations: a
      case study.
AB  - It is widely acknowledged that sexual boundary violations by a faculty member at
      an analytic institute damage the local analytic community in ways that can
      reverberate for years. Yet little has been written about the process of
      institutional recovery. With one exception, a paper published after the major
      protagonists had died, no actual case studies are to be found in the literature.
      In 2010 a senior training analyst at a psychoanalytic training program abruptly
      resigned under the cloud of a presumed sexual boundary violation. Seventeen
      months later, an APsaA Committee on Institutes site visit presented a unique
      opportunity to study the institutional trauma and recovery process as they
      unfolded. This report highlights the importance of recognizing and working
      through the expectable institutional resistance to processing the trauma. This
      enables a sensitive response to the various constituencies that have been
      affected and allows the integrity of the institute to be restored. 

PMID- 23963186
TI  - The ability of stroke volume variation measured by a noninvasive cardiac output
      monitor to predict fluid responsiveness in mechanically ventilated children.
AB  - Continuous noninvasive cardiac output monitoring (NICOM) is a clinically useful
      tool in the pediatric setting. This study compared the ability of stroke volume
      variation (SVV) measured by NICOM with that of respiratory variations in the
      velocity of aortic blood flow (?Vpeak) and central venous pressure (CVP) to
      predict of fluid responsiveness in mechanically ventilated children after
      ventricular septal defect repair. The study investigated 26 mechanically
      ventilated children after the completion of surgery. At 30 min after their
      arrival in an intensive care unit, a colloid solution of 10 ml/kg was
      administrated for volume expansion. Hemodynamic variables, including CVP, stroke
      volume, and ?Vpeak in addition to cardiac output and SVV in NICOM were measured
      before and 10 min after volume expansion. The patients with a stroke volume
      increase of more than 15 % after volume expansion were defined as responders. The
      26 patients in the study consisted of 13 responders and 13 nonresponders. Before
      volume expansion, ?Vpeak and SVV were higher in the responders (both p values
      <0.001). The areas under the receiver operating characteristic curves of ?Vpeak,
      SVV, and CVP were respectively 0.956 (95 % CI 0.885-1.00), 0.888 (95 % CI 0.764
      1.00), and 0.331 (95 % CI 0.123-0.540). This study showed that SVV by NICOM and
      ?Vpeak by echocardiography, but not CVP, reliably predicted fluid responsiveness
      during mechanical ventilation after ventricular septal defect repair in children.

PMID- 23963187
TI  - The SCN5A mutation A1180V is associated with electrocardiographic features of
      LQT3.
AB  - Mutations of the SCN5A gene are associated with several arrhythmic syndromes
      including the Brugada syndrome, conduction disease, long QT syndrome type 3
      (LQT3), atrial fibrillation, and dilated cardiomyopathy. We report LQT3
      associated with an A1180V cardiac sodium channel mutation, previously associated
      with cardiac conduction block, and dilated cardiomyopathy in three generations of
      a Chinese family. Clinical, electrocardiographic (ECG), and echocardiographic
      examination was followed by direct sequencing of SCN5A and HERG to screen genomic
      DNA from blood samples. The proband presented with multiple syncopes from the age
      of 7 years and was found to share a mutation with two other members of his
      family. Continuous ECG monitoring after presentation showed prolonged QTc and
      biphasic T waves, multiple episodes of ventricular tachycardia and torsades de
      pointes. The other two mutation carriers showed ECG features of LQT3 without
      clinical symptoms. Transthoracic echocardiography showed normal cardiac structure
      in all three mutation carriers. This study shows LQT3 features associated with an
      A1180V cardiac sodium channel mutation, expanding the spectrum of phenotypes
      resulting from this mutation in which biophysical study has shown a persistent
      late Na(+) current. 

PMID- 23963189
TI  - Stereochemical lability of azatitanacyclopropanes: dynamic kinetic resolution in
      reductive cross-coupling reactions with allylic alcohols.
AB  - Azatitanacyclopropanes (titanaziridines) are shown to be stereochemically labile
      under reaction conditions for reductive cross-coupling. This fundamental property
      has been employed to realize highly selective asymmetric coupling reactions with
      allylic alcohols that proceed by dynamic kinetic resolution. 

PMID- 23963190
TI  - Thermoelectrical modeling of bipolar coagulation on posterior spinal artery in a
      porcine spinal surgery model.
AB  - The primary objective of our study was to develop a thermoelectrical model with
      both solid and liquid phases to calculate tissue temperature during bipolar
      coagulation of a posterior spinal artery on the spinal cord. Control of thermal
      spread caused by coagulation is a concern in spinal surgery. This model utilizes
      a nonisothermal flow to account for the heat transfer due to the movement of
      cerebrospinal fluid that is induced by electrical field and temperature gradient.
      The model is validated by in situ temperature measurements on a porcine spinal
      cord model. The maximum error for tissue temperature of this model is 12.6%, and
      the overall average error is 4.2%. The lesional region (>50 degrees C) is
      identified to be as wide as 5 mm, and thermal dose cumulative equivalent minutes
      at 43 degrees C (CEM 43) is also calculated with this model. The incorporation of
      nonisothermal flow has been shown to be crucial in order to accurately predict
      thermal dose in tissue. The developed model can be further used to establish a
      guideline for the use of bipolar coagulation. 

PMID- 23963191
TI  - A joint-constraint model-based system for reconstructing total knee motion.
AB  - Comprehending knee motion is an essential requirement for studying the causes of
      knee disorders. In this paper, we propose a new 2-D-3-D registration system based
      on joint-constraint model for reconstructing total knee motion. The proposed
      model that contains bone geometries and an articulated joint mechanism is first
      constructed from multipostural magnetic resonance volumetric images. Then, the
      bone segments of the model are hierarchically registered to each frame of the
      given single-plane fluoroscopic video that records the knee activity. The bone
      posture is iteratively optimized using a modified chamfer matching algorithm to
      yield the simulated radiograph which is the best fit to the underlying
      fluoroscopic image. Unlike conventional registration methods computing posture
      parameters for each bone independently, the proposed femorotibial and
      patellofemoral joint models properly maintain the articulations between femur,
      tibia, and patella during the registration processes. As a result, we can obtain
      a sequence of registered knee postures showing smooth and reasonable physiologic
      patterns of motion. The proposed system also provides joint-space interpolation
      to densely generate intermediate postures for motion animation. The effectiveness
      of the proposed method was validated by computer simulation, animal cadaver, and
      in vivo knee testing. The mean target registration errors for femur, tibia, and
      patella were less than 1.5 mm. In particular, small out-of-plane registration
      errors [less than 1 mm (translation) and 2 degrees  (rotation)] were achieved in
      animal cadaver assessments. 

PMID- 23963188
TI  - Nongenetic risk factors and congenital heart defects.
AB  - Advances have been made in identifying genetic etiologies of congenital heart
      defects. Through this knowledge, preventive strategies have been designed and
      instituted, and prospective parents are counseled regarding their risk of having
      an affected child. Great strides have been made in genetic variant
      identification, and genetic susceptibility to environmental exposures has been
      hypothesized as an etiology for congenital heart defects. Unfortunately, similar
      advances in understanding have not been made regarding strategies to prevent
      nongenetic risk factors. Less information is available regarding the potential
      adverse effect of modifiable risk factors on the fetal heart. This review
      summarizes the available literature on these modifiable exposures that may alter
      the risk for congenital heart disease. Information regarding paternal
      characteristics and conditions, maternal therapeutic drug exposures, parental
      nontherapeutic drug exposures, and parental environmental exposures are
      presented. Factors are presented in terms of risk for congenital heart defects as
      a group. These factors also are broken down by specific defect type. Although
      additional investigations are needed in this area, many of the discussed risk
      factors present an opportunity for prevention of potential disease. 

PMID- 23963192
TI  - Assessing the Need for Referral in Automatic Diabetic Retinopathy Detection.
AB  - Emerging technologies in health care aim at reducing unnecessary visits to
      medical specialists, minimizing overall cost of treatment and optimizing the
      number of patients seen by each doctor. This paper explores image recognition for
      the screening of diabetic retinopathy, a complication of diabetes that can lead
      to blindness if not discovered in its initial stages. Many previous reports on DR
      imaging focus on the segmentation of the retinal image, on quality assessment,
      and on the analysis of presence of DR-related lesions. Although this study has
      advanced the detection of individual DR lesions from retinal images, the simple
      presence of any lesion is not enough to decide on the need for referral of a
      patient. Deciding if a patient should be referred to a doctor is an essential
      requirement for the deployment of an automated screening tool for rural and
      remote communities. We introduce an algorithm to make that decision based on the
      fusion of results by metaclassification. The input of the metaclassifier is the
      output of several lesion detectors, creating a powerful high-level feature
      representation for the retinal images. We explore alternatives for the bag-of
      visual-words (BoVW)-based lesion detectors, which critically depends on the
      choices of coding and pooling the low-level local descriptors. The final
      classification approach achieved an area under the curve of 93.4% using SOFT-MAX
      BoVW (soft-assignment coding/max pooling), without the need of normalizing the
      high-level feature vector of scores. 

PMID- 23963193
TI  - Pediatric oncology nursing research goes global.

PMID- 23963194
TI  - Experiences of parents with the physical care needs at home of children with
      cancer: a qualitative study.
AB  - BACKGROUND: Between cancer treatment courses, children who have not developed any
      complications or neutropenia are sent home until the start of the next treatment
      protocol. OBJECTIVE: The aim of this study was to describe the experiences of
      parents in the home care of children who had been recently diagnosed with cancer
      and were undergoing cancer treatment but had been discharged from the hospital
      between treatment protocols. METHODS: The study was carried out at Ege
      University, Turkey. Twelve parents of 12 children between 0 and 18 years of age
      participated in an in-depth interview. The data were analyzed according to Orem's
      Self-care Deficit Theory. RESULTS: The main themes were basic conditioning
      factors, self-care agency, and self-care needs. Some parents changed their place
      of residence because of the cancer treatment, focused on the recovery of the
      child, and experienced fear, perception difficulties, and difficulties related to
      self-care needs. CONCLUSIONS: Parents report difficulties with extreme emotions
      and dilemmas in maintaining their daily routines of life secondary to fear of
      infection and challenges with feeding their children. IMPLICATIONS FOR NURSING: A
      well-planned discharge education, home visits, and telephone consultation
      interventions are essential to meet the needs of children and their parents who
      are at home between treatment courses.

PMID- 23963195
TI  - Adolescents' and young adults' experiences of childhood cancer: descriptions of
      daily life 5 years after diagnosis.
AB  - BACKGROUND: Survivors of childhood cancer are a growing population in society.
      These young people have a high risk of developing chronic health problems with a
      potential strong impact on their lives. How a childhood cancer experience affects
      survivors in adolescence has been studied to a limited extent; an increased
      understanding of this young group is needed to improve follow-up care. OBJECTIVE:
      The aim of this study was to gain a deeper understanding of how childhood cancer
      affects the lives of survivors by exploring adolescents' and young adults' views
      of what it is like living with this experience. METHODS: Fifty-nine 11- to 22
      year-olds were interviewed a median of 5 years after a cancer diagnosis (response
      rate, 66%). Data were collected through telephone interviews and were analyzed
      using qualitative content analysis techniques. RESULTS: Three groups of
      informants were identified according to their descriptions of the influence of
      cancer treatment on their daily life: "feeling like anyone else" (informants who
      described that the cancer experience had almost no influence on current life)
      (49%), "feeling almost like others" (those who described some influence) (44%),
      and "feeling different" (those describing a great influence on current life)
      (7%). CONCLUSIONS: Most of the adolescents and young adults appear to get along
      well, although many informants described that life was affected to some extent by
      having had cancer. IMPLICATIONS FOR PRACTICE: Follow-up care is needed that can
      identify those young survivors of childhood cancer having trouble with daily life
      and offer them support to strengthen their resources in managing difficulties in
      relation to having had cancer.

PMID- 23963197
TI  - Family members' retrospective stories of the treatment stage of an adolescent or
      young adult who subsequently died of cancer.
AB  - BACKGROUND: Adolescents and young adults (AYAs) with cancer have been recognized
      as being disadvantaged within the present healthcare system. This article is part
      of a major study that was motivated by the principal researcher's own experience
      of her 17-year-old son dying of cancer and from current literature that
      highlights the lack of support and understanding of AYAs and their families.
      OBJECTIVE: This article aimed to uncover from the stories of family members the
      experience after the treatment of an adolescent or young adult family member
      (aged 13-23 years) who subsequently died. METHODS: Narrative inquiry was
      determined to be the appropriate methodology for this study. The participants
      were a self-selected purposeful sample of 26 family members whose narratives
      spoke of experience of having an AYA family member live with and die of cancer.
      RESULTS: The meta-narrative of the families' stories in the treatment stage
      resulted in 6 themes. This article provides the insights of experience of the
      family members within the treatment stage. The family members speak of a health
      system unable to respond to the AYA and family member's needs and the suffering
      sacrifice and courage of the AYAs and the family members. CONCLUSION: There is
      evidence that AYAs and family members are lost in the system, with minimum
      understanding or support for this unique group of people. IMPLICATIONS FOR
      PRACTICE: Further research is required to assist the development of evidence
      based best practice models of care for AYAs and their families.

PMID- 23963198
TI  - Assessment of physical performance using the 6-minute walk test in children
      receiving treatment for cancer.
AB  - BACKGROUND: The study of physical performance in children with cancer is emerging
      as an important variable in symptom research. Studies have shown that children
      with cancer experience deficits in physical performance during treatment that may
      be present years after therapy. OBJECTIVE: The aim of this study was to determine
      if distance on the 6-minute walk test (6MWT) changed in children during the first
      3 cycles of cancer treatment and to compare the distances walked with healthy
      norms. METHODS: This is a secondary data analysis of 19 boys and 10 girls, aged 6
      to 17 years, who were newly diagnosed with cancer and were part of a larger study
      that measured changes in fatigue and physical performance during the first 3
      cycles of chemotherapy. Participants performed the 6MWT between days 15 and 29 of
      the first and third cycles of chemotherapy. RESULTS: Pediatric cancer patients
      did not have a significant change in the distance walked at cycle 3 of
      chemotherapy compared with cycle 1. When compared with 2 different normative data
      sets for healthy children, most children with cancer performed significantly
      below their peers. CONCLUSIONS: Children had poor strength and endurance after 3
      cycles of chemotherapy even when their disease was responding to treatment.
      Interventions are needed to promote rehabilitation and maintenance of physical
      performance, as both are important to quality of life and ongoing child
      development. IMPLICATIONS FOR PRACTICE: Children receiving cancer treatment who
      are ambulatory may appear to be functioning normally but are in fact severely
      deconditioned compared with their healthy peers.

PMID- 23963199
TI  - Lewis base assisted B-H bond redistribution in borazine and polyborazylene.
AB  - Lewis bases react with borazine and polyborazylene, yielding borane adducts. In
      the case of NH3 (l), ammonia-borane (AB) is formed and quantified using NMR
      spectroscopy against an internal standard. Calculations indicate that the
      formation of B(NH2)3 may provide the driving force of this redistribution. Given
      the complexity and expense of currently known spent AB regeneration pathways, it
      is suggested that this redistribution chemistry be used to recover AB and improve
      regeneration methods. 

PMID- 23963200
TI  - Bilateral myoid hamartoma of breast: an exceptionally rare lesion.
AB  - Breast hamartomas (BH) or Fibroadenolipoma are extremely rare breast lesions.
      They are benign, focal malformations that resemble a neoplasm in the tissue of
      its origin. We describe a case of a 48 year old woman with bilateral breast lumps
      for the past 18 months and 6 months which were gradually increasing in size. FNAC
      smears revealed only clusters of benign ductal epithelial cells. Lumps were
      excised and histopathology revealed predominantly stromal smooth muscle bundles
      (proved by immunohistochemistry) along with scattered intact terminal duct
      lobular units, dilated ducts and entrapped islands of mature fibroadipose tissue.
      A diagnosis of Bilateral Myoid hamartoma of breast was given. To the best of our
      knowledge till date no case of bilateral MH of breast has been reported in the
      literature. We report the first case of bilateral MBH highlighting its morpho
      immunophenotypic features. 

PMID- 23963202
TI  - Dielectric relaxations and conduction mechanisms in polyether-clay composite
      polymer electrolytes under high carbon dioxide pressure.
AB  - The composite material P(EO/EM)-Sa consisting of synthetic saponite (Sa)
      dispersed in poly[ethylene oxide-co-2-(2-methoxyethoxy)ethyl glycidyl ether]
      (P(EO/EM)) is studied by "in situ" measurements using broadband electrical
      spectroscopy (BES) under pressurized CO2 to characterize the dynamic behavior of
      conductivity and the dielectric relaxations of the ion host polymer matrix. It is
      revealed that there are three dielectric relaxation processes associated with:
      (I) the dipolar motions in the short oxyethylene side chains of P(EO/EM) (beta);
      and (II) the segmental motion of the main chains comprising the polyether
      components (alphafast, alphaslow). alphaslow is attributed to the slow alpha
      relaxation of P(EO/EM) macromolecules, which is hindered by the strong
      coordination interactions with the ions. Two conduction processes are observed,
      sigmaDC and sigmaID, which are attributed, respectively, to the bulk conductivity
      and the interdomain conductivity. The temperature dependence of conductivity and
      relaxation processes reveals that alphafast and alphaslow are strongly correlated
      with sigmaDC and sigmaID. The "in situ" BES measurements under pressurized CO2
      indicate a fast decrease in sigmaDC at the initial CO2 treatment time resulting
      from the decrease in the concentration of polyether-M(n+) complexes, which is
      driven by the CO2 permeation. The relaxation frequency (fR) of alphaslow at the
      initial CO2 treatment time increases and shows a steep rise with time with the
      same behavior of the alphafast mode. It is demonstrated that the interactions
      between polyether chains of P(EO/EM) and cations in the polymer electrolyte
      layers embedded in Sa are probably weakened by the low permittivity of CO2
      (epsilon = 1.08). Thus, the formation of ion pairs in the polymer electrolyte
      domains of P(EO/EM)-Sa occurs, with a corresponding reduction in the
      concentration of ion carriers.

PMID- 23963203
TI  - Solid-state graft copolymer electrolytes for lithium battery applications.
AB  - Battery safety has been a very important research area over the past decade.
      Commercially available lithium ion batteries employ low flash point (< 80 
      degrees C), flammable, and volatile organic electrolytes. These organic based
      electrolyte systems are viable at ambient temperatures, but require a cooling
      system to ensure that temperatures do not exceed 80  degrees C. These cooling
      systems tend to increase battery costs and can malfunction which can lead to
      battery malfunction and explosions, thus endangering human life. Increases in
      petroleum prices lead to a huge demand for safe, electric hybrid vehicles that
      are more economically viable to operate as oil prices continue to rise. Existing
      organic based electrolytes used in lithium ion batteries are not applicable to
      high temperature automotive applications. A safer alternative to organic
      electrolytes is solid polymer electrolytes. This work will highlight the
      synthesis for a graft copolymer electrolyte (GCE) poly(oxyethylene) methacrylate
      (POEM) to a block with a lower glass transition temperature (Tg)
      poly(oxyethylene) acrylate (POEA). The conduction mechanism has been discussed
      and it has been demonstrated the relationship between polymer segmental motion
      and ionic conductivity indeed has a Vogel-Tammann-Fulcher (VTF) dependence.
      Batteries containing commercially available LP30 organic (LiPF6 in ethylene
      carbonate (EC):dimethyl carbonate (DMC) at a 1:1 ratio) and GCE were cycled at
      ambient temperature. It was found that at ambient temperature, the batteries
      containing GCE showed a greater overpotential when compared to LP30 electrolyte.
      However at temperatures greater than 60  degrees C, the GCE cell exhibited much
      lower overpotential due to fast polymer electrolyte conductivity and nearly the
      full theoretical specific capacity of 170 mAh/g was accessed.

PMID- 23963205
TI  - A theoretical study of the mechanisms of oxidation of ethylene by manganese oxo
      complexes.
AB  - The mechanisms of oxidation of ethylene by manganese-oxo complexes of the type
      MnO3L (L = O(-), Cl, CH3, OCH3, Cp, NPH3) have been explored on the singlet,
      doublet, triplet and quartet potential energy surfaces at the B3LYP/LACVP* level
      of theory and the results discussed and compared with those of the technetium and
      rhenium oxo complexes we reported earlier, thereby drawing group trends in the
      reactions of this important class of oxidation catalysts. In the reactions of
      MnO3L (L = O(-), Cl(-), CH3, OCH3, Cp, NPH3) with ethylene, it was found that the
      formation of the dioxylate intermediate along the concerted [3 + 2] addition
      pathway on the singlet potential energy is favored kinetically and
      thermodynamically over its formation by a two-step process via the metallaoxetane
      by [2 + 2] addition. The activation barriers for the formation of the dioxylate
      and the product stabilities on the singlet PES for the ligands studied are found
      to follow the order: NPH3 < Cl(-) < CH3O(-) < Cp < O(-) < CH3. On the doublet
      PES, the activation barriers for the formation of the dioxylate intermediate for
      the ligands are found to follow the order: CH3O(-) < Cl(-) < Cp < CH3 while the
      order of product stabilities is: Cl(-) < CH3O(-) < Cp < CH3. The order of
      dioxylate product stabilities on the triplet surface for the ligands studied is:
      Cl(-) < CH3O(-) < Cp < CH3 < NPH3 < O(-) and the order on the quartet surface is
      O(-) < Cp < CH3 < NPH3 < Cl(-) < CH3O(-). The re-arrangement of the
      metallaoxetane intermediate to the dioxylate is not a feasible reaction for all
      the ligands studied. Of the group VII B metal oxo complexes studied, MnO4(-) and
      MnO3(OCH3) appear to be the best catalysts for the exclusive formation of the
      dioxylate intermediate, MnO3(OCH3) being better so on both kinetic and
      thermodynamic grounds. The best epoxidation catalyst for the Mn complexes is
      MnO3Cl; the formation of the epoxide precursor will not result from the reaction
      of LMnO3 (L = O(-), Cp) with ethylene on any of the surfaces studied. The trends
      observed for the oxidation reactions of the Mn complexes with ethylene compare
      closely with those reported by us for the ReO3L and TcO3L (L = O(-), Cl, CH3,
      OCH3, Cp, NPH3) complexes, but there is far greater similarity between the Re and
      Tc complexes than between Mn and either of the other two. There does not appear
      to be any singlet-triplet or doublet-quartet spin-crossover in any of the
      pathways studied. 

PMID- 23963204
TI  - Assessment of pharmacokinetic interactions of the HCV NS5A replication complex
      inhibitor daclatasvir with antiretroviral agents: ritonavir-boosted atazanavir,
      efavirenz and tenofovir.
AB  - BACKGROUND: Approximately one-third of all HIV-infected individuals are
      coinfected with HCV, many of whom will receive concomitant treatment for both
      infections. With the advent of direct-acting antivirals (DAAs) for HCV, potential
      drug interactions between antiretrovirals and DAAs require evaluation prior to co
      therapy. METHODS: Three open-label studies were conducted in healthy subjects to
      assess potential interactions between the investigational first-in-class HCV NS5A
      replication complex inhibitor daclatasvir and representative antiretrovirals
      atazanavir/ritonavir, efavirenz and tenofovir disoproxil fumarate. RESULTS:
      Target exposure was that of 60 mg daclatasvir alone. Dose-normalized (60 mg)
      geometric mean ratios of daclatasvir AUCtau for 20 mg +/- atazanavir/ritonavir
      (2.10 [90% CI 1.95, 2.26]) and 120 mg +/- efavirenz (0.68 [0.60, 0.78]) showed
      less than the three-fold elevation and two-fold reduction, respectively, in
      systemic exposure predicted by prior interaction studies with potent
      inhibitors/inducers of CYP3A4. Daclatasvir dose adjustment to 30 mg once daily
      with atazanavir/ritonavir and 90 mg once daily with efavirenz is predicted to
      normalize AUCtau relative to the target exposure (geometric mean ratios 1.05
      [0.98, 1.13] and 1.03 [0.90, 1.16], respectively). Atazanavir exposure (Cmax,
      AUCtau and C24 trough) and efavirenz Ctrough under coadministration were similar
      to historical data without daclatasvir. No clinically relevant interactions
      between daclatasvir and tenofovir disoproxil fumarate were observed for either
      drug, and no dosing adjustments were indicated. Daclatasvir was well tolerated in
      all three studies. CONCLUSIONS: The pharmacokinetic data support coadministration
      of daclatasvir with atazanavir/ritonavir, efavirenz and/or tenofovir. A Phase III
      study in HIV-HCV coinfection has commenced using the described dose
      modifications.

PMID- 23963206
TI  - Locally advanced verrucous carcinoma of the oral cavity: treatment using
      customized mold HDR brachytherapy instead of hemi-maxillectomy.
AB  - BACKGROUND: Oral verrucous carcinomas are locally invasive but rarely
      metastasize. Current treatment options include surgery and external beam
      radiotherapy (EBRT). In medical inoperable patients or irresectable tumors, high
      dose-rate (HDR) brachytherapy is a valid alternative. CASE: We present an 85-year
      old man with functionally irresectable cT3N0M0 verrucous carcinoma superficially
      spreading along the upper alveolar ridge to the retro-alveolar triangle, with
      infiltration of the left soft and hard palate and buccal mucosa. Using a
      customized intraoral mold, this patient was treated with HDR brachytherapy
      delivering a dose of 48 Gy in 12 fractions three times per week. Treatment was
      well tolerated, and after prolonged confluent mucositis the tumor is in complete
      remission. REVIEW OF LITERATURE AND CONCLUSION: The scarce literature on
      customized mold HDR brachytherapy in maxillary tumors is reviewed and
      recommendations for other head and neck tumors are given.

PMID- 23963207
TI  - [Optimal timing of surgery for rectal cancer after neoadjuvant chemoradiotherapy:
      which patients would benefit from waiting?].

PMID- 23963208
TI  - [Evaluation of (balloon) brachytherapy for partial breast irradiation in breast
      cancer based on current meta-analyses].

PMID- 23963211
TI  - Reinventing bioinnovation.
AB  - The landscape for bioinnovation is undergoing a seismic shift as drug developers,
      regulators, academic institutions, and government research organizations adapt to
      the formidable challenge of bringing new medicines to market. The inability to
      translate current advances in the scientific understanding of disease into new
      therapeutics is forcing all sectors to replace traditional drug development
      paradigms with newer and more efficient models. This issue of Clinical
      Pharmacology & Therapeutics explores these changes to the bioinnovation
      ecosystem.

PMID- 23963215
TI  - The PCAST report on pharmaceutical innovation: implications for the FDA.
AB  - In September 2012, the President's Council of Advisors on Science and Technology
      (PCAST) released the report "Propelling Innovation in Drug Discovery, Development
      and Evaluation." A product of discussions with many stakeholders, the report
      reiterates current problems in drug development, including diminished return on
      basic biomedical research. The report calls for doubling the current annual
      output of innovative new medicines--an ambitious goal. Recommendations and
      resulting initiatives will probably affect the FDA's drug regulatory programs.

PMID- 23963214
TI  - Anecdotes from ITMAT: building capacity for translational science.

PMID- 23963216
TI  - The PCAST report: impact and implications for the pharmaceutical industry.
AB  - The President's Council of Advisors on Science and Technology (PCAST) report sets
      out an ambitious goal: to double the output of innovative, new medicines with
      increased efficacy and safety within the next 10-15 years. If attainable, this
      could change the face of medicine and bring great benefit to society. Clear
      leadership, commitment to action, and unprecedented collaboration will be
      essential if the goal of the report is to be realized.

PMID- 23963217
TI  - Are drug labels static or dynamic?
AB  - Understanding drug metabolism is essential for identifying drug-drug interactions
      (DDIs). As new data concerning a drug's pharmacokinetics arise, updates to drug
      labels and administration procedures should rapidly follow. However, the US Food
      and Drug Administration (FDA) has inconsistently updated drug labels, based on
      new research findings (i.e., in peer-reviewed publications). In this Commentary,
      we highlight recent findings on the metabolism of imatinib and argue for a more
      stringent protocol for updating drug labels.

PMID- 23963218
TI  - Regulatory review: How do agencies ensure the quality of decision making?
AB  - The Centre for Innovation in Regulatory Science (CIRS) Workshop on Regulatory
      Review brought together international regulators and multinational pharmaceutical
      company representatives to focus on best practices that underlie regulatory
      decision making, thereby facilitating the transparent, timely, procedurally
      predictable, and good-quality evaluation of new medicines. Participants
      investigated frameworks used by agencies, discussed challenges for regulatory
      agencies in making quality decisions, investigated the role of other
      stakeholders, and made recommendations of activities and processes that agencies
      and companies can consider to enable quality decision making.

PMID- 23963219
TI  - Legal foundations of adaptive licensing.
AB  - In April 2012, MIT's Center for Biomedical Innovation and the European Medicines
      Agency (EMA) cosponsored a workshop on legal foundations of adaptive
      pharmaceuticals licensing. Past and present attorneys from the US Food and Drug
      Administration (FDA), the EMA, and Health Sciences Agency Singapore (HSA) found
      that existing statutes provided authority for adaptive licensing (AL). By
      contrast, an attorney from Health Canada identified gaps in authority.
      Reimbursement during initial phases of adaptive approaches to licensing was
      deemed consistent with existing statutes in all jurisdictions.

PMID- 23963220
TI  - Genomic taxonomy of the genus prochlorococcus.
AB  - The genus Prochlorococcus is globally abundant and dominates the total
      phytoplankton biomass and production in the oligotrophic ocean. The single
      species, Prochlorococcus marinus, comprises six named ecotypes. Our aim was to
      analyze the taxonomic structure of the genus Prochlorococcus. We analyzed the
      complete genomes of 13 cultured P. marinus type and reference strains by means of
      several genomic taxonomy tools (i.e., multilocus sequence analysis, amino acid
      identity, Karlin genomic signature, and genome to genome distance). In addition,
      we estimated the diversity of Prochlorococcus species in over 100 marine
      metagenomes from all the major oceanic provinces. According to our careful
      taxonomic analysis, the 13 strains corresponded, in fact, to ten different
      Prochlorococcus species. This analysis establishes a new taxonomic framework for
      the genus Prochlorococcus. Further, the analysis of the metagenomic data suggests
      that, in total, there may only be 35 Prochlorococcus species in the world's
      oceans. We propose that the dearth of species observed in this study is driven by
      high selective pressures that limit diversification in the global ocean. 

PMID- 23963221
TI  - Impacts of mariculture on the diversity of bacterial communities within
      intertidal sediments in the Northeast of China.
AB  - Mariculture is one of the major seafood supplies worldwide and has caused serious
      environmental concerns on the coastal zone. Its rapid development has been shown
      to disrupt the sediment ecosystems and thus influence the benthic bacterial
      communities. Bacterial diversity and community structure within both adjacent
      farms and non-cultured zones intertidal sediments along the coasts of Qinhuangdao
      and Dalian, China, were investigated using full-length 16S rRNA gene-based T-RFLP
      analyses and clone library construction. Richness and Shannon-Wiener index were
      significantly increased at sites adjacent the mariculture farm with mean values
      of 29 and 2.97 from peak profiles of T-RFLP result. Clustering analyses suggested
      that impacts of mariculture on bacterial diversity of sediment were significantly
      larger than those resulted from temporal and spatial scales. Upon comparisons of
      RFLP patterns from 602 clones from libraries of the selected five samples, 137
      OTUs were retrieved. Members of gamma- and delta-Proteobacteria, Bacilli,
      Flavobacteria, and Actinobacteria were recorded in all libraries. In addition,
      gamma-Proteobacteria were dominant in all samples (21.7~45.0 %). Redundancy
      analysis revealed that the distribution of bacterial composition seemed to be
      determined by the variables of salinity, PO4 (3-)-P, NH4 (+)-N, and Chlorophyll a
      content. The phyla of gamma-Proteobacteria, Clostridia, Flavobacteria, Bacilli,
      and Planctomycetes were principal components to contribute to the bacterial
      differences of clone libraries. Our finding demonstrated that these phyla could
      display variations of bacterial composition linked to environmental disturbance
      resulted from mariculture. 

PMID- 23963222
TI  - Bacterial diversity of surface sand samples from the Gobi and Taklamaken deserts.
AB  - Arid regions represent nearly 30 % of the Earth's terrestrial surface, but their
      microbial biodiversity is not yet well characterized. The surface sands of
      deserts, a subset of arid regions, are generally subjected to large temperature
      fluctuations plus high UV light exposure and are low in organic matter. We
      examined surface sand samples from the Taklamaken (China, three samples) and Gobi
      (Mongolia, two samples) deserts, using pyrosequencing of PCR-amplified 16S V1/V2
      rDNA sequences from total extracted DNA in order to gain an assessment of the
      bacterial population diversity. In total, 4,088 OTUs (using >=97 % sequence
      similarity levels), with Chao1 estimates varying from 1,172 to 2,425 OTUs per
      sample, were discernable. These could be grouped into 102 families belonging to
      15 phyla, with OTUs belonging to the Firmicutes, Proteobacteria, Bacteroidetes,
      and Actinobacteria phyla being the most abundant. The bacterial population
      composition was statistically different among the samples, though members from 30
      genera were found to be common among the five samples. An increase in phylotype
      numbers with increasing C/N ratio was noted, suggesting a possible role in the
      bacterial richness of these desert sand environments. Our results imply an
      unexpectedly large bacterial diversity residing in the harsh environment of these
      two Asian deserts, worthy of further investigation. 

PMID- 23963223
TI  - The combination of different carbon sources enhances bacterial growth efficiency
      in aquatic ecosystems.
AB  - The dissolved organic carbon (DOC) pool is composed of several organic carbon
      compounds from different carbon sources. Each of these sources may support
      different bacterial growth rates, but few studies have specifically analyzed the
      effects of the combination of different carbon sources on bacterial metabolism.
      In this study, we evaluated the response of several metabolic parameters,
      including bacterial biomass production (BP), bacterial respiration (BR),
      bacterial growth efficiency (BGE), and bacterial community structure, on the
      presence of three DOC sources alone and in combination. We hypothesized that the
      mixture of different DOC sources would increase the efficiency of carbon use by
      bacteria (BGE). We established a full-factorial substitutive design (seven
      treatments) in which the effects of the number and identity of DOC sources on
      bacterial metabolism were evaluated. We calculated the expected metabolic rates
      of the combined DOC treatments based on the single-DOC treatments and observed a
      positive interaction on BP, a negative interaction on BR, and, consequently, a
      positive interaction on BGE for the combinations. The bacterial community
      composition appeared to have a minor impact on differences in bacterial
      metabolism among the treatments. Our data indicate that mixtures of DOC sources
      result in a more efficient biological use of carbon. This study provides strong
      evidence that the mixture of different DOC sources is a key factor affecting the
      role of bacteria in the carbon flux of aquatic ecosystems. 

PMID- 23963224
TI  - Effects of riparian plant diversity loss on aquatic microbial decomposers become
      more pronounced with increasing time.
AB  - We examined the potential long-term impacts of riparian plant diversity loss on
      diversity and activity of aquatic microbial decomposers. Microbial assemblages
      were obtained in a mixed-forest stream by immersion of mesh bags containing three
      leaf species (alder, oak and eucalyptus), commonly found in riparian corridors of
      Iberian streams. Simulation of species loss was done in microcosms by including a
      set of all leaf species, retrieved from the stream, and non-colonized leaves of
      three, two or one leaf species. Leaves were renewed every month throughout six
      months, and microbial inoculum was ensured by a set of colonized leaves from the
      previous month. Microbial diversity, leaf mass loss and fungal biomass were
      assessed at the second and sixth months after plant species loss. Molecular
      diversity of fungi and bacteria, as the total number of operational taxonomic
      units per leaf diversity treatment, decreased with leaf diversity loss. Fungal
      biomass tended to decrease linearly with leaf species loss on oak and eucalyptus,
      suggesting more pronounced effects of leaf diversity on lower quality leaves.
      Decomposition of alder and eucalyptus leaves was affected by leaf species
      identity, mainly after longer times following diversity loss. Leaf decomposition
      of alder decreased when mixed with eucalyptus, while decomposition of eucalyptus
      decreased in mixtures with oak. Results suggest that the effects of leaf
      diversity on microbial decomposers depended on leaf species number and also on
      which species were lost from the system, especially after longer times. This may
      have implications for the management of riparian forests to maintain stream
      ecosystem functioning. 

PMID- 23963225
TI  - ACOEM practice guidelines: elbow disorders.
AB  - OBJECTIVE: The American College of Occupational and Environmental Medicine has
      updated the treatment guidelines in its Elbow Disorders chapter through revision
      processes begun in 2006. This abbreviated version of that chapter highlights some
      of the evidence and recommendations developed. METHODS: Comprehensive systematic
      literature reviews were accomplished with article abstraction, critiquing,
      grading, evidence table compilation, and guideline finalization by a
      multidisciplinary expert panel and extensive peer-review to develop evidence
      based guidance. Consensus recommendations were formulated when evidence was
      lacking and often relied on analogy to other disorders for which evidence exists.
      A total of 108 high- or moderate-quality trials were identified for elbow
      disorders. RESULTS: Guidance has been developed for 13 major diagnoses and
      includes 270 specific recommendations. CONCLUSION: Quality evidence is now
      available to guide treatment for elbow disorders, particularly for lateral
      epicondylalgia.

PMID- 23963226
TI  - Genetic screens: Pol II interactions in detail.

PMID- 23963227
TI  - Error estimates for (semi-)empirical dispersion terms and large
      biomacromolecules.
AB  - The first-principles modeling of biomaterials has made tremendous advances over
      the last few years with the ongoing growth of computing power and impressive
      developments in the application of density functional theory (DFT) codes to large
      systems. One important step forward was the development of dispersion corrections
      for DFT methods, which account for the otherwise neglected dispersive van der
      Waals (vdW) interactions. Approaches at different levels of theory exist, with
      the most often used (semi-)empirical ones based on pair-wise interatomic C6R(-6)
      terms. Similar terms are now also used in connection with semiempirical QM (SQM)
      methods and density functional tight binding methods (SCC-DFTB). Their basic
      structure equals the attractive term in Lennard-Jones potentials, common to most
      force field approaches, but they usually use some type of cutoff function to make
      the mixing of the (long-range) dispersion term with the already existing (short
      range) dispersion and exchange-repulsion effects from the electronic structure
      theory methods possible. All these dispersion approximations were found to
      perform accurately for smaller systems, but error estimates for larger systems
      are very rare and completely missing for really large biomolecules. We derive
      such estimates for the dispersion terms of DFT, SQM and MM methods using error
      statistics for smaller systems and dispersion contribution estimates for the
      PDBbind database of protein-ligand interactions. We find that dispersion terms
      will usually not be a limiting factor for reaching chemical accuracy, though some
      force fields and large ligand sizes are problematic. 

PMID- 23963228
TI  - Fusion of median and bilateral filtering for range image upsampling.
AB  - We present a new upsampling method to enhance the spatial resolution of depth
      images. Given a low-resolution depth image from an active depth sensor and a
      potentially high-resolution color image from a passive RGB camera, we formulate
      it as an adaptive cost aggregation problem and solve it using the bilateral
      filter. The formulation synergistically combines the median and bilateral filters
      thus it better preserves the depth edges and is more robust to noise. Numerical
      and visual evaluations on a total of 37 Middlebury data sets demonstrate the
      effectiveness of our method. A real-time high-resolution depth capturing system
      is also developed using commercial active depth sensor based on the proposed
      upsampling method. 

PMID- 23963229
TI  - Anticoagulation in patients with traumatic brain injury.
AB  - PURPOSE OF REVIEW: A major challenge in the treatment of brain-injured patients
      is the decision on indication and timing of prophylactic anticoagulation. In
      addition, an increasing number of patients suffering from traumatic brain injury
      (TBI) are on preinjury anticoagulation therapy. Despite clear evidence for an
      increased risk of venous thromboembolic events and pulmonary embolism in
      traumatized patients without prophylactic anticoagulation, there is a lack of
      distinct recommendations and standardized clinical practice guidelines. This
      review summarizes current research evidence regarding post-traumatic prophylactic
      anticoagulation and management of patients with prehospital use of
      anticoagulants. RECENT FINDINGS: In addition to nonpharmacological techniques
      like compression stockings, use of low-dose unfractionated heparin or low
      molecular-weight heparin is effective in different studies in terms of
      thromboprophylaxis. If follow-up computed tomography scans and clinical
      neurological examinations do not show progression within 24 h after initial
      evaluation, prophylactic anticoagulation does not increase risk for hemorrhage
      progression and therefore seems to be safe after TBI. SUMMARY: Stratification
      scores for identification of TBI patients with low, moderate, or high risk for
      spontaneous cerebral bleeding may help to allow early thromboprophylaxis while
      maintaining a good risk-benefit ratio. So far, these scores require validation by
      prospective trials. Therefore, current evidence requires control computed
      tomography scans prior to early pharmacological thromboprophylaxis.

PMID- 23963230
TI  - Transcranial doppler and near infrared spectroscopy in the perioperative period.
AB  - PURPOSE OF REVIEW: Maintenance of adequate blood flow and oxygen to the brain is
      one of the principal endpoints of all surgery and anesthesia. During operations
      in general anesthesia, however, the brain is at particular risk for silent
      ischemia. Despite this risk, the brain still remains one of the last monitored
      organs in clincial anesthesiology. RECENT FINDINGS: Transcranial Doppler (TCD)
      sonography and near-infrared spectroscopy (NIRS) experience a revival as these
      noninvasive technologies help to detect silent cerebral ischemia. TCD allows for
      quantification of blood flow velocities in basal intracranial arteries. TCD
      derived variables such as the pulsatility index might hint toward diminished
      cognitive reserve or raised intracranial pressure. NIRS allows for assessment of
      regional cerebral oxygenation. Monitoring should be performed during high-risk
      surgery for silent cerebral ischemia and special circumstances during critical
      care medicine. Both techniques allow for the assessment of cerebrovascular
      autoregulation and individualized management of cerebral hemodynamics. SUMMARY:
      TCD and NIRS are noninvasive monitors that anesthesiologists apply to tailor
      cerebral oxygen delivery, aiming to safeguard brain function in the perioperative
      period.

PMID- 23963231
TI  - Minimally invasive lumbar decompression: a treatment for lumbar spinal stenosis.
AB  - PURPOSE OF REVIEW: Percutaneous lumbar decompression is a minimally invasive
      procedure for the treatment of symptomatic lumbar spinal stenosis (LSS). The
      purpose of this article is to review the current literature on percutaneous
      lumbar decompression as well as review the safety and outcomes associated with
      the procedure. RECENT FINDINGS: LSS is a significant cause of chronic pain and a
      common indication for invasive spine surgery. The recent literature shows that
      percutaneous lumbar decompression is a minimally invasive treatment option that
      affords a high level of safety, improved function, decreased pain scores, and is
      cost-effective. SUMMARY: This minimally invasive procedure is an option for
      patients with central canal LSS who have continued pain-following conservative
      treatment such as physical therapy, oral medications, and lumbar spine
      injections. Percutaneous lumbar decompression is a procedure that bridges the gap
      between invasive surgery and more conservative treatment for LSS. This
      percutaneous technique provides increasing options to those patients with central
      canal lumbar stenosis who may not be candidates for an invasive decompression
      procedure. Overall, this procedure has been found to be well tolerated and
      effective in reducing pain while generally improving function.

PMID- 23963232
TI  - Anesthesia for transsphenoidal pituitary surgery.
AB  - PURPOSE OF REVIEW: Pituitary tumors are commonly encountered in clinical
      practice. Patients with functioning adenomas frequently present with symptoms of
      hormone excess, whereas those with nonfunctioning adenomas often present later
      and have symptoms resulting from mass effect of the tumor. This article examines
      recent advancements in the preoperative assessment and anesthetic management of
      patients undergoing transsphenoidal pituitary surgery. RECENT FINDINGS:
      Endoscopic guidance has improved tumor visualization while minimizing the risk of
      nasal and dental complications and septal perforation. Computer-assisted
      navigation and intraoperative MRI has further improved surgical outcomes. Airway
      management may be particularly challenging in patients with acromegaly or
      Cushing's disease. Both intravenous and volatile agents can be used for
      anesthetic maintenance. Although pituitary surgery can be intensely stimulating
      and associated with intraoperative hypertension, most patients require little
      postoperative analgesia. Postoperative diabetes insipidus is common after
      pituitary surgery and is typically self-limited. Some patients will require
      treatment with desmopressin and it is important to avoid 'overshoot' iatrogenic
      syndrome of inappropriate antidiuretic hormone SIADH and hyponatremia in these
      patients. CONCLUSION: Anesthetic management for pituitary surgery requires
      thorough preanesthetic assessment of hormonal function and intraoperative
      management to facilitate surgical exposure while providing hemodynamic stability
      and allowing for rapid emergence.

PMID- 23963233
TI  - Ultrasound guidance, a win-win approach to peripheral nerve blockade.
AB  - PURPOSE OF REVIEW: The objective of the current review is to examine the
      likelihood of improved safety in peripheral nerve blockade attributable to
      ultrasound guidance. RECENT FINDINGS: With ultrasound guidance, a 10-fold
      reduction in the incidence of local anesthetic systemic toxicity as well as a
      tendency toward less long-term neuropathies are shown. SUMMARY: Ultrasound is
      clearly superior to other techniques with the aim of achieving maximum efficacy
      with minimum risk: a win-win approach.

PMID- 23963234
TI  - [Shared-housing arrangements for care-dependent people in Germany. A literature
      overview of structures, outcomes and quality management].
AB  - A main factor for the development of shared-housing arrangements (SHA) was the
      wish of more self-determination in old age. Since January 2013 SHA is government
      funded through the "Pflege-Neuausrichtungs-Gesetz" (PNG). Yet, an overview of the
      situation of SHA in Germany is not available. Therefore, a systematic literature
      search (databases CareLit, CINAHL, GeroLit, PubMed) was conducted in order to
      identify publications regarding resident- and care-specific characteristics,
      resident-related health outcomes and setting-specific quality management systems.
      The currently available knowledge in these fields is not exhaustive and further
      research is needed. The results indicate that care in SHA is not more efficient
      regarding residents' quality of life than in institutional care settings. Valid
      studies regarding the quality of care provision in SHA and conceptual basics
      concerning quality assessment are widely lacking. Thus, the goal of expanding SHA
      within the framework of the PNG has to be accompanied by in-depth health services
      research. 

PMID- 23963235
TI  - Defective HIV-1 quasispecies in the form of multiply drug-resistant proviral DNA
      within cells can be rescued by superinfection with different subtype variants of
      HIV-1 and by HIV-2 and SIV.
AB  - OBJECTIVES: HIV-1 generates swarms of similar, but genetically distinct, variants
      termed quasispecies and many of these variants can be defective. A relevant
      question is whether such defective species can contribute to viral pathogenesis.
      Indeed, we previously reported that a presumed recombination of defective
      proviral DNA with other complementary defective proviral DNA or with wild-type
      viral DNA in the aftermath of superinfection could lead to the rescue of
      defective provirus and the production of replication-competent virus. We then
      wished to determine whether such rescue could be affected by viruses of different
      subtypes or even by other members of the retrovirus family. METHODS: Here, we
      have used drug resistance mutations within the HIV genome as markers of potential
      recombination. RESULTS: We show that a defective proviral DNA within cells can be
      rescued by the superinfection of MT2 cells by various subtypes of HIV-1, and by
      HIV-2 and simian immunodeficiency virus, but not by human T cell leukaemia virus
      type 1 or by human herpes virus-6. The drug-resistance phenotype of the rescued
      HIV was confirmed in a second round of infection. CONCLUSIONS: Defective proviral
      HIV-1 can be rescued by the infection by different variants of HIV-1 and by
      several other retroviruses as well.

PMID- 23963236
TI  - Evolution toward high-level fluoroquinolone resistance in Francisella species.
AB  - OBJECTIVES: Francisella tularensis, a CDC class A potential bioterrorism agent,
      is a Gram-negative bacterium responsible for tularaemia. Understanding the
      mechanisms of resistance to antibiotics used as first-line treatment is of major
      security relevance. METHODS: We propagated the three parental reference strains
      Francisella tularensis subsp. holarctica live vaccine strain, Francisella
      novicida and Francisella philomiragia with increasing concentrations of
      ciprofloxacin, a fluoroquinolone used as curative and prophylactic treatment for
      tularaemia. This evolution procedure provided us with high-level ciprofloxacin
      resistant mutants and all evolutionary intermediates towards high-level
      resistance. We determined the resistance levels to other fluoroquinolones
      (levofloxacin and moxifloxacin) and other antibiotic families (aminoglycosides,
      tetracyclines and macrolides) and characterized the genetic changes in the
      fluoroquinolone target genes encoding DNA gyrase and topoisomerase IV. RESULTS:
      All high-level resistant mutants shared cross-resistance to the tested
      fluoroquinolones, while some also revealed striking levels of cross-resistance to
      other clinically relevant antibiotic classes. High-level resistant mutants
      carried one to three mutations, including some not previously reported. We mapped
      all mutations onto known topoisomerase three-dimensional structures. Along the
      pathways towards high-level resistance, we identified complex evolutionary
      trajectories including polymorphic states and additional resistance mechanisms
      likely to be associated with efflux processes. CONCLUSIONS: Our data demonstrated
      the efficiency and speed of in vitro production of mutants highly resistant to
      fluoroquinolones in Francisella species. They emphasize the urgent need to
      identify all antibiotic resistance mechanisms in these species, develop molecular
      tools for their detection and design new therapeutic alternatives for tularaemia.

PMID- 23963244
TI  - Flexible access to conformationally-locked bicyclic morpholines.
AB  - A preparatively accessible route to a series of conformationally-locked bicyclic
      morpholines has been developed. This flexible approach allows for diversification
      in order for a small array of lead-like scaffolds to be synthesised from readily
      available key building blocks. 

PMID- 23963246
TI  - Enhanced Raman signals from switchable nanoparticle probes.
AB  - We demonstrate here a DNA-based conformationally switchable nanodumbell structure
      that modulates the interparticle distance between two gold-silver core-shell
      nanoparticles to induce significant changes in the SERS signal. 

PMID- 23963247
TI  - Continuous wavelet transform based partial least squares regression for
      quantitative analysis of Raman spectrum.
AB  - Quantitative analysis of Raman spectra using surface-enhanced Raman scattering
      (SERS) nanoparticles has shown the potential and promising trend of development
      in in vivo molecular imaging. Partial least square regression (PLSR) methods have
      been reported as state-of-the-art methods. However, the approaches fully rely on
      the intensities of Raman spectra and can not avoid the influences of the unstable
      background. In this paper we design a new continuous wavelet transform based PLSR
      (CWT-PLSR) algorithm that uses mixing concentrations and the average CWT
      coefficients of Raman spectra to carry out PLSR. We elaborate and prove how the
      average CWT coefficients with a Mexican hat mother wavelet are robust
      representations of Raman peaks, and the method can reduce the influences of
      unstable baseline and random noises during the prediction process. The algorithm
      was tested using three Raman spectra data sets with three cross-validation
      methods in comparison with current leading methods, and the results show its
      robustness and effectiveness. 

PMID- 23963248
TI  - A novel and efficient synthesis of diverse dihydronaphtho[1,2-b]furans using the
      ceric ammonium nitrate-catalyzed formal [3 + 2] cycloaddition of 1,4
      naphthoquinones to olefins and its application to furomollugin.
AB  - A novel approach was developed for the synthesis of diverse dihydronaphtho[1,2
      b]furans from 1,4-naphthoquinones and olefins in the presence of ceric ammonium
      nitrate. This reaction provides a rapid route for the synthesis of a variety of
      dihydronaphtho[1,2-b]furans and naphtho[1,2-b]furans bearing different
      substituents. This methodology was also used to synthesize the biologically
      important natural product furomollugin in only 2 steps. 

PMID- 23963249
TI  - Use of glomerular filtration rate estimating equations for drug dosing in HIV
      positive patients.
AB  - BACKGROUND: Current HIV treatment guidelines recommend using the Cockcroft-Gault
      equation for drug dosing adjustments. The use of newer glomerular filtration rate
      (GFR) estimating equations for drug dosing and the appropriateness of physician
      antiretroviral dosing based on estimated kidney function have not been studied in
      an HIV-positive population. METHODS: We evaluated concordance between measured
      and estimated GFR for the assignment of kidney function categories designated by
      the US Food and Drug Administration (FDA) Guidance for industry for
      pharmacokinetic studies, and appropriateness of physician antiretroviral drug
      dosing for level of kidney function in 200 HIV-positive patients on stable
      antiretroviral therapy. Estimated kidney function was determined using the
      Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI), Modification of Diet
      in Renal Disease (MDRD) Study and Cockcroft-Gault equations. RESULTS: For
      assignment of FDA-designated kidney function categories, concordance rates
      between measured and estimated GFR using the CKD-EPI, MDRD Study and Cockcroft
      Gault equations were 79%, 71% and 77%, respectively. This pattern was consistent
      across most subgroups. When actual prescribed dosages were compared with
      recommended dosages based on the level of estimated kidney function, 3-19% of
      study participants were prescribed higher than recommended dosages. The largest
      discordance between prescribed and recommended dosages was observed for the
      Cockcroft-Gault equation. CONCLUSIONS: The CKD-EPI equation has the highest
      concordance with measured GFR for the assignment of FDA-designated kidney
      function categories. Its use may lead to lower dosing-related errors in HIV
      infected US adults on stable antiretroviral therapy. More education is required
      with respect to dose adjustment for level of kidney function.

PMID- 23963250
TI  - Structure and isomerization comparison of Zn(II), Cd(II) and Hg(II) perchlorate
      complexes of 2,6-bis([(2-pyridyl-methyl)amino]methyl)pyridine.
AB  - The divalent zinc triad perchlorate coordination chemistry of 2,6-bis([(2-pyridyl
      methyl)amino]methyl)pyridine (L) was investigated by X-ray crystallography and
      solution state (1)H NMR. New complexes [HgL(ClO4)2] (1) and [CdL(ClO4)2] (2) were
      isolated as bicapped distorted square pyramidal racemates, contrasting with the
      approximate trigonal bipyramidal structure of [ZnL](ClO4)2 (3). Although rapid
      inter- and intramolecular exchange is common for simple complexes of zinc triad
      metal ions, conditions for slow intramolecular isomerization on both the delta
      and J(HH) time scales were established for 1, 2 and 3. Trends in geminal (1)H
      coupling suggested that an asymmetric structure was favored for all three metal
      ions at or below 40  degrees C. Contributions of a symmetric structure to
      solution equilibria were both temperature- and metal ion-dependent. Spectral
      trends were consistent with interconversion of a pair of enantiomeric square
      pyramidal ligand conformers through a symmetric trigonal bipyramidal ligand
      conformer by M-N bond cleavage and nitrogen inversion. Racemization was slower
      than the coupling constant time scale up to 40  degrees C for all complexes.
      Differential stabilization of specific small ligand conformations in solution has
      potential toxicological significance.

PMID- 23963251
TI  - Simple and efficient technique for the preparation of testicular cell
      suspensions.
AB  - Mammalian testes are very complex organs that contain over 30 different cell
      types, including somatic testicular cells and different stages of germline cells.
      This heterogeneity is an important drawback concerning the study of the bases of
      mammalian spermatogenesis, as pure or enriched cell populations in certain stages
      of sperm development are needed for most molecular analyses. Various strategies
      such as Staput, centrifugal elutriation, and flow cytometry (FC) have been
      employed to obtain enriched or purified testicular cell populations in order to
      enable differential gene expression studies. It is required that cells are in
      suspension for most enrichment/ purification approaches. Ideally, the cell
      suspension will be representative of the original tissue, have a high proportion
      of viable cells and few multinucleates--which tend to form because of the
      syncytial nature of the seminiferous epithelium--and lack cell clumps . Previous
      reports had evidenced that testicular cell suspensions prepared by an exclusively
      mechanical method clumped more easily than trypsinized ones. On the other hand,
      enzymatic treatments with RNAses and/or disaggregating enzymes like trypsin and
      collagenase lead to specific macromolecules degradation, which is undesirable for
      certain downstream applications. The ideal process should be as short as possible
      and involve minimal manipulation, so as to achieve a good preservation of
      macromolecules of interest such as mRNAs. Current protocols for the preparation
      of cell suspensions from solid tissues are usually time-consuming, highly
      operator-dependent, and may selectively damage certain cell types . The protocol
      presented here combines the advantages of a highly reproducible and extremely
      brief mechanical disaggregation with the absence of enzymatic treatment, leading
      to good quality cell suspensions that can be used for flow cytometric analysis
      and sorting, and ulterior gene expression studies.

PMID- 23963252
TI  - Clinical and regulatory features of drugs not initially approved by the FDA.
AB  - US Food and Drug Administration (FDA) denials of New Drug Applications (NDAs) are
      often controversial, yet little is known about the basis and characteristics of
      these decisions. We reviewed new drugs and biologics evaluated by FDA advisory
      committees between 2007 and 2009 and found that half (27/52, 52%) were unapproved
      in the first cycle. By 2013, 63% had been approved. Products with initial safety
      concerns (62%) were much more likely to be approved eventually than drugs with
      efficacy concerns (8%). 

PMID- 23963253
TI  - Characterization of the federal workforce at the Centers for Disease Control and
      Prevention.
AB  - CONTEXT: Studies characterizing the public health workforce are needed for
      providing the evidence on which to base planning and policy decision making both
      for workforce staffing and for addressing uncertainties regarding organizing,
      financing, and delivering effective public health strategies. The Centers for
      Disease Control and Prevention (CDC) is leading the enumeration of the US public
      health workforce with an initial focus on CDC as the leading federal public
      health agency. OBJECTIVE: To characterize CDC's workforce, assess retirement
      eligibility and potential staff losses, and contribute these data as the federal
      component of national enumeration efforts. METHODS: Two sources containing data
      related to CDC employees were analyzed. CDC's workforce was characterized by
      using data elements recommended for public health workforce enumeration and
      categorized the occupations of CDC staff into 15 standard occupational
      classifications by using position titles. Retirement eligibility and potential
      staffing losses were analyzed by using 1-, 3-, and 5-year increments and compared
      these data across occupational classifications to determine the future impact of
      potential loss of workforce. RESULTS: As of the first quarter of calendar year
      2012, a total 11 223 persons were working at CDC; 10 316 were civil servants, and
      907 were Commissioned Corps officers. Women accounted for 61%. Public health
      managers, laboratory workers, and administrative-clerical staff comprised the top
      3 most common occupational classifications among CDC staff. Sixteen percent of
      the workforce was eligible to retire by December 2012, and more than 30% will be
      eligible to retire by December 2017. CONCLUSIONS: This study represents the first
      characterization of CDC's workforce and provides an evidence base upon which to
      develop policies for ensuring an ongoing ability to fulfill the CDC mission of
      maintaining and strengthening the public's health. Establishing a system for
      continually monitoring the public health workforce will support future efforts in
      understanding workforce shortages, capacity, and effectiveness; projecting
      trends; and initiating policies.

PMID- 23963254
TI  - The relationship between county-level contextual characteristics and use of
      diabetes care services.
AB  - OBJECTIVES: To examine the relationship between county-level measures of social
      determinants and use of preventive care among US adults with diagnosed diabetes.
      To inform future diabetes prevention strategies. METHODS: Data are from the
      Behavioral Risk Factor Surveillance System (BRFSS) 2004 and 2005 surveys, the
      National Diabetes Surveillance System, and the Area Resource File. Use of
      diabetes care services was defined by self-reported receipt of 7 preventive care
      services. Our study sample included 46 806 respondents with self-reported
      diagnosed diabetes. Multilevel models were run to assess the association between
      county-level characteristics and receipt of each of the 7 preventive diabetes
      care service after controlling for characteristics of individuals. Results were
      considered significant if P < .05. RESULTS: Controlling for individual-level
      characteristics, our analyses showed that 7 of the 8 county-level factors
      examined were significantly associated with use of 1 or more preventive diabetes
      care services. For example, people with diabetes living in a county with a high
      uninsurance rate were less likely to have an influenza vaccination, visit a
      doctor for diabetes care, have an A1c test, or a foot examination; people with
      diabetes living in a county with a high physician density were more likely to
      have an A1c test, foot examination, or an eye examination; and people with
      diabetes living in a county with more people with less than high-school education
      were less likely to have influenza vaccination, pneumococcal vaccination, or self
      care education (all P < .05). CONCLUSIONS: Many of the county-level factors
      examined in this study were found to be significantly associated with use of
      preventive diabetes care services. County policy makers may need to consider
      local circumstances to address the disparities in use of these services.

PMID- 23963255
TI  - Navigating the maze: ethics approval pathways for intellectual disability
      research.

PMID- 23963256
TI  - Evolving legal responses to dependence on families in New Zealand and Singapore
      healthcare.
AB  - Healthcare decision-making has traditionally focused on individual autonomy, but
      there is now a change occurring in which the involvement of families is gaining
      prominence. This appears to stem from an increasing emphasis on relational
      aspects of autonomy which recognises the individual's connectedness to their
      family, and also state reliance upon families to share the burdens and costs of
      caring for elderly and disabled dependents. Such a reorientation calls for
      similar legal emphasis on patient autonomy as understood in relational terms, and
      one that offers more adequate conceptions of independence, confidentiality and
      decision-making authority in the light of this change. This paper outlines how
      two common law jurisdictions, New Zealand and Singapore, have accommodated, or
      are responding to, these changes. 

PMID- 23963257
TI  - The first survey of attitudes of medical students in Ireland towards termination
      of pregnancy.
AB  - BACKGROUND: Since the UK Abortion Act (1967), women have travelled from Ireland
      to the UK for legal abortion. In 2011 >4000 women did so. Knowledge and attitudes
      of medical students towards abortion have been published, however, this is the
      first such report from Ireland. OBJECTIVE: To investigate medical students'
      attitudes towards abortion in Ireland. METHODS: All medical students at the
      University of Limerick, and physicians who graduated from the university within
      the previous 12 months, were invited via email to complete an anonymous online
      survey. The questionnaire comprised 17 questions. Quantitative and qualitative
      analyses were performed. RESULTS: Response rate was 45% (n=169; 55% women; 88.2%
      <30 years of age; 66.7% Irish; 29.2% North American). Outcomes were: abortion
      should not be legally available (7.1%), abortion should be allowed in limited
      circumstances only (35.5%), abortion should be legally available upon request
      (55%). 72.8% of respondents were moderately/strongly prochoice (74% of women/71%
      of men/72% and 76% of Irish and North American respondents, respectively).
      Students aged >30 years were less likely to be prochoice (55%). While 95.2%
      believed that education on abortion should be offered within medical school
      curricula, 28.8% stated that they would decline to terminate pregnancies even if
      legally permitted. While 58.8% indicated that they might perform legal abortions
      once qualified, 25.7% would do so under limited circumstances only. CONCLUSIONS:
      The majority of participants wanted education regarding abortion. Despite being
      predominantly prochoice, considerably fewer students, irrespective of
      nationality, indicated that they would perform abortions.

PMID- 23963258
TI  - Noninvasive Optical Monitoring of Bladder Filling to Capacity Using a Wireless
      Near Infrared Spectroscopy Device.
AB  - Lack of bladder fullness sensation is an issue that arises in different
      neurogenic conditions and in addition to influencing patients' quality of life,
      can result in serious kidney damage. We describe a wireless wearable sensor for
      detecting bladder fullness using near infrared spectroscopy (NIRS). The sensor
      has been tested in vitro and in vivo to verify its feasibility and is shown to be
      capable of detecting changes in bladder content noninvasively.

PMID- 23963259
TI  - Current issues in dengue vaccination.
AB  - PURPOSE OF REVIEW: Dengue is a global health problem and of concern to travelers
      and deploying military personnel, with development and licensure of an effective
      tetravalent dengue vaccine a public health priority. The recent performance of
      the lead dengue vaccine in a phase 2b efficacy trial underscores dengue vaccine
      development challenges. This review focuses on current issues in dengue
      vaccination. RECENT FINDINGS: The dengue viruses (DENVs) are mosquito-borne
      flaviviruses transmitted by infected Aedes mosquitoes. Illness manifests across a
      clinical spectrum with severe disease characterized by intravascular volume
      depletion and hemorrhage. Recent estimates on the burden of DENV infection
      determined that there are 390 million dengue infections per year, three times the
      current estimate by the WHO. There are no licensed antivirals or vaccines to
      treat or prevent dengue though many are in preclinical or clinical development.
      DENV illness results from a complex interaction of viral properties and host
      immune responses. Immunologic complexity, lack of an adequate animal model of
      disease, absence of an immune correlate of protection, and only partially
      informative immunogenicity assays are challenging dengue vaccine development
      efforts. SUMMARY: Dengue vaccine development efforts have numerous complex
      challenges to overcome before a well tolerated and effective vaccine is licensed
      and available. In this review, the authors discuss the current issues in dengue
      vaccination.

PMID- 23963262
TI  - Exclusive formation of SnO by low temperature single-source AACVD.
AB  - An easily synthesised Sn(II) bis(ureide) derivative is shown to be a single
      source precursor for the aerosol-assisted CVD of SnO, providing unprecedented
      levels of oxidation state control at temperatures as low as 250  degrees C.

PMID- 23963261
TI  - [Vertigo in children and adolescents. Part 1: Epidemiology and diagnosis of
      peripheral vestibular disorders].
AB  - Migraine equivalents are the most common cause of vertigo in children and
      adolescents. Vertigo and balance disorders occur frequently in children during
      the course of otitis media, middle ear effusion and viral infections. If otitis
      media is associated with reduced hearing and vertigo, labyrinthitis must be
      considered. Craniocerebral injury is another important cause of vertigo in
      children. In contrast, spontaneous benign paroxysmal positional vertigo is rare
      among children. The isolated cases of endolymphatic hydrops that occur in
      children are usually secondary. Perilymph fistula can have congenital, infectious
      or trauma-related causes. The following characteristics are useful for
      differentiating between different vertiginous syndromes: type and duration of
      vertigo, triggering/aggravating/alleviating factors and accompanying symptoms. A
      neuro-ophthalmologic examination is essential to rule out central vestibular
      disorders. 

PMID- 23963260
TI  - Brucellosis in low-income and middle-income countries.
AB  - PURPOSE OF REVIEW: Human brucellosis is a neglected, underrecognized infection of
      widespread geographic distribution. It causes acute febrile illness and a
      potentially debilitating chronic infection in humans, and livestock infection has
      substantial socioeconomic impact. This review describes new information regarding
      the epidemiology of brucellosis in the developing world and advances in diagnosis
      and treatment. RECENT FINDINGS: The highest recorded incidence of human
      brucellosis occurs in the Middle East and Central Asia. Fever etiology studies
      demonstrate brucellosis as a cause of undifferentiated febrile illness in the
      developing world. Brucellosis is a rare cause of fever among returning travelers,
      but is more common among travelers returning from the Middle East and North
      Africa. Sensitive and specific rapid diagnostic tests appropriate for resource
      limited settings have been validated. Randomized controlled trials demonstrate
      that optimal treatment for human brucellosis consists of doxycycline and an
      aminoglycoside. Decreasing the burden of human brucellosis requires control of
      animal brucellosis, but evidence to inform the design of control programs in the
      developing world is needed. SUMMARY: Brucellosis causes substantial morbidity in
      human and animal populations. While improvements in diagnostic options for
      resource-limited settings and stronger evidence for optimal therapy should
      enhance identification and treatment of human brucellosis, prevention of human
      disease through control in animals remains paramount.

PMID- 23963263
TI  - PageRank tracker: from ranking to tracking.
AB  - Video object tracking is widely used in many real-world applications, and it has
      been extensively studied for over two decades. However, tracking robustness is
      still an issue in most existing methods, due to the difficulties with adaptation
      to environmental or target changes. In order to improve adaptability, this paper
      formulates the tracking process as a ranking problem, and the PageRank algorithm,
      which is a well-known webpage ranking algorithm used by Google, is applied.
      Labeled and unlabeled samples in tracking application are analogous to query
      webpages and the webpages to be ranked, respectively. Therefore, determining the
      target is equivalent to finding the unlabeled sample that is the most associated
      with existing labeled set. We modify the conventional PageRank algorithm in three
      aspects for tracking application, including graph construction, PageRank vector
      acquisition and target filtering. Our simulations with the use of various
      challenging public-domain video sequences reveal that the proposed PageRank
      tracker outperforms mean-shift tracker, co-tracker, semiboosting and beyond
      semiboosting trackers in terms of accuracy, robustness and stability. 

PMID- 23963264
TI  - Photocatalytic surface patterning of cellulose using diazonium salts and visible
      light.
AB  - Coumarin-functionalized cellulose sheets were chemically modified using a visible
      light catalyzed "Photo-Meerwein" arylation. Use of a photomask to pattern the
      surface resulted in directly visible images. 

PMID- 23963266
TI  - Multifocal skeletal tuberculosis presenting as paraplegia: a case report.
AB  - BACKGROUND: Tuberculosis of the musculoskeletal system is not a common clinical
      condition; however, multifocal bone involvement is even rarer and difficult to
      recognize. CASE: In this paper, we presented a patient who developed paraplegia
      15 days before his hospital admission. He was operated by neurosurgeons due to
      spinal mass, but postoperative examination revealed vertebral and multifocal
      skeletal tuberculosis. It is difficult to diagnose this condition by conventional
      imaging methods. The importance of positron emission tomography (PET) in the
      diagnosis of skeletal tuberculosis was emphasized. RESULT: The importance of
      rehabilitation program in restoring functionality was overviewed in the light of
      current literature. Vertebral and osteoarticular tuberculosis should be
      considered in patients with vertebral and thoracic mass presenting with
      neurological deficits.

PMID- 23963265
TI  - Metabolic labeling of newly transcribed RNA for high resolution gene expression
      profiling of RNA synthesis, processing and decay in cell culture.
AB  - The development of whole-transcriptome microarrays and next-generation sequencing
      has revolutionized our understanding of the complexity of cellular gene
      expression. Along with a better understanding of the involved molecular
      mechanisms, precise measurements of the underlying kinetics have become
      increasingly important. Here, these powerful methodologies face major limitations
      due to intrinsic properties of the template samples they study, i.e. total
      cellular RNA. In many cases changes in total cellular RNA occur either too slowly
      or too quickly to represent the underlying molecular events and their kinetics
      with sufficient resolution. In addition, the contribution of alterations in RNA
      synthesis, processing, and decay are not readily differentiated. We recently
      developed high-resolution gene expression profiling to overcome these
      limitations. Our approach is based on metabolic labeling of newly transcribed RNA
      with 4-thiouridine (thus also referred to as 4sU-tagging) followed by rigorous
      purification of newly transcribed RNA using thiol-specific biotinylation and
      streptavidin-coated magnetic beads. It is applicable to a broad range of
      organisms including vertebrates, Drosophila, and yeast. We successfully applied
      4sU-tagging to study real-time kinetics of transcription factor activities,
      provide precise measurements of RNA half-lives, and obtain novel insights into
      the kinetics of RNA processing. Finally, computational modeling can be employed
      to generate an integrated, comprehensive analysis of the underlying molecular
      mechanisms. 

PMID- 23963267
TI  - Older adults present better back endurance than young adults during a dynamic
      trunk extension exercise.
AB  - BACKGROUND AND OBJECTIVE: Poor back endurance is a predictor of low back pain.
      Few studies have investigated back muscle fatigue in older people. The purpose of
      this study was to compare the back muscle fatigue by endurance time and perceived
      effort between young and older adults during dynamic exercise. METHOD: Sixteen
      older and 16 young adults, all healthy, participated in this study. The subjects
      performed a fatiguing trunk extension-flexion exercise on a Roman chair until
      exhaustion. Endurance time and perceived muscle fatigue (Borg CR-10 scale) were
      used as fatigue criteria. RESULTS: The older adults were significantly
      (T<formula>_{(30)}</formula> = -2,073; p = 0.039) more resistant to back muscle
      fatigue (time in mean 133 +/- 52 s) than the young adults (mean 97 +/- 27 s). In
      general, both groups had the same perception of high-level fatigue during the
      exercise bout (T<formula>_{(29)}</formula> = 1.73; p=0.092). CONCLUSION: The
      older adults presented better back endurance than young adults during a dynamic
      trunk extension exercise. These results have implications for back endurance in
      the primary prevention of low back pain in both young and older adults.

PMID- 23963268
TI  - Assessment of forward head posture in females: observational and photogrammetry
      methods.
AB  - BACKGROUND: There are different methods to assess forward head posture (FHP) but
      the accuracy and discrimination ability of these methods are not clear.
      OBJECTIVES: Here, we want to compare three postural angles for FHP assessment and
      also study the discrimination accuracy of three photogrammetric methods to
      differentiate groups categorized based on observational method. METHOD: All
      Seventy-eight healthy female participants (23 +/- 2.63 years), were classified
      into three groups: moderate-severe FHP, slight FHP and non FHP based on
      observational postural assessment rules. Applying three photogrammetric methods -
      craniovertebral angle, head title angle and head position angle - to measure FHP
      objectively. RESULTS: One - way ANOVA test showed a significant difference in
      three categorized group's craniovertebral angle (P< 0.05, F=83.07). There was no
      dramatic difference in head tilt angle and head position angle methods in three
      groups. According to Linear Discriminate Analysis (LDA) results, the canonical
      discriminant function (Wilks'Lambda) was 0.311 for craniovertebral angle with
      79.5% of cross-validated grouped cases correctly classified. CONCLUSION: Our
      results showed that, craniovertebral angle method may discriminate the females
      with moderate-severe and non FHP more accurate than head position angle and head
      tilt angle. The photogrammetric method had excellent inter and intra rater
      reliability to assess the head and cervical posture.

PMID- 23963269
TI  - Postural control and low back pain in elite athletes comparison of static balance
      in elite athletes with and without low back pain.
AB  - Although current research findings suggest that postural control or static
      balance is impaired in subjects with low back pain, few studies have specifically
      addressed the effect of low back pain on static balance in elite athletes. Forty
      four athletes belonging to Chilean national teams took part in this study; 20 had
      low back pain and the remaining 24 were healthy controls. Displacement of the
      centre of pressure was analyzed by computerized platform posturography, using a
      standardized protocol; subjects were required to stand upright on both feet, with
      eyes first open then closed. The results showed that, athletes with low back pain
      used significantly more energy (p< 0.0182) and had a greater displacement of the
      centre of pressure (p< 0.005) with open eyes to control posture than healthy
      athletes. It may be concluded that static balance is impaired in elite athletes
      with low back pain and that analysis of two-footed stance provides a sensitive
      assessment of static balance in athletes. 

PMID- 23963270
TI  - Concentric and eccentric strength of trunk muscles in osteitis pubis soccer
      players.
AB  - BACKGROUND AND OBJECTIVES: Osteitis pubis refers to a painful, inflammatory
      condition involving the pubic bones, pubic symphysis, and adjacent structures.
      So, the aims of the study were to evaluate the strength of trunk muscles of
      soccer players suffering from osteitis pubis, and to compare the
      agonist/antagonist ratio of trunk muscles in osteitis pubis athletes with that of
      healthy athletes. MATERIALS AND METHODS: Twenty-five soccer male athletes with
      osteitis pubis, and 25 healthy soccer athletes. Peak torque/body weight (PT/BW)
      was recorded from trunk muscles during isokinetic concentric and eccentric
      contraction modes at a speed of 120 degrees /s for healthy and osteitis pubis
      soccer players. RESULTS: There was a significant decrease in concentric
      contraction of back muscles in osteitis pubis group (p=0.01). A significant
      decrease in eccentric contraction of abdominal muscles was also recorded in
      osteitis pubis group (p=0.008). Concentric abdominal/back muscles ratio was
      significantly higher in osteitis pubis group (p=0.016), with no significant
      difference in eccentric abdominal/back muscles ratio between both groups
      (p>0.05). CONCLUSION: Osteitis pubis group displayed concentric weakness of back
      muscle and eccentric weakness of abdominal muscles that lead to disturbance of
      the normal concentric abdominal/back ratio.

PMID- 23963271
TI  - Tributyl phosphate biodegradation to butanol and phosphate and utilization by a
      novel bacterial isolate, Sphingobium sp. strain RSMS.
AB  - A Sphingobium sp. strain isolated from radioactive solid waste management site
      (RSMS) completely degraded 7.98 g/L of tributyl phosphate (TBP) from TBP
      containing suspensions in 3 days. It also completely degraded 20 mM dibutyl
      phosphate (DBP) within 2 days. The strain tolerated high levels of TBP and showed
      excellent stability with respect to TBP degradation over several repeated
      subcultures. On solid minimal media or Luria Bertani media supplemented with TBP,
      the RSMS strain showed a clear zone of TBP degradation around the colony. Gas
      chromatography and spectrophotometry analyses identified DBP as the intermediate
      and butanol and phosphate as the products of TBP biodegradation. The RSMS strain
      utilized both TBP and DBP as the sole source of carbon and phosphorous for its
      growth. The butanol released was completely utilized by the strain as a carbon
      source thereby leaving no toxic residue in the medium. Degradation of TBP or DBP
      was found to be suppressed by high concentration of glucose which also inhibited
      TBP or DBP dependent growth. The results highlight the potential of Sphingobium
      sp. strain RSMS for bioremediation of TBP and for further molecular
      investigation. 

PMID- 23963272
TI  - Impact of initial conditions on extant microbial kinetic parameter estimates:
      application to chlorinated ethene dehalorespiration.
AB  - Monod kinetics are the foundation of mathematical models of many environmentally
      important biological processes, including the dehalorespiration of chlorinated
      ethene groundwater contaminants. The Monod parameters--qmax, the maximum specific
      substrate utilization rate, and KS, the half-saturation constant--are typically
      estimated in batch assays, which are superficially simple to prepare and
      maintain. However, if initial conditions in batch assays are not chosen
      carefully, it is unlikely that the estimated parameter values will be meaningful
      because they do not reflect microbial activity in the environmental system of
      interest, and/or they are not mathematically identifiable. The estimation of qmax
      and KS values that are highly correlated undoubtedly contributes significantly to
      the wide range in reported parameter values and may undermine efforts to use
      mathematical models to demonstrate the occurrence of natural attenuation or
      predict the performance of engineered bioremediation approaches. In this study, a
      series of experimental and theoretical batch kinetic assays were conducted using
      the tetrachloroethene-respirer Desulfuromonas michiganensis to systematically
      evaluate the effects of initial batch assay conditions, expressed as the initial
      substrate (S0)-to-initial biomass concentration (X0) ratio (S0/X0) and the S0/KS
      ratio on parameter correlation. An iterative approach to obtain meaningful Monod
      parameter estimates was developed and validated using three different strains and
      can be broadly applied to a range of other substrates and populations. While the
      S0/X0 ratio is critical to obtaining kinetic parameter estimates that reflect in
      situ microbial activity, this study shows that optimization of the S0/KS ratio is
      key to minimizing Monod parameter correlation.

PMID- 23963273
TI  - Improved detection of antibiotic compounds by bacterial reporter strains achieved
      by manipulations of membrane permeability and efflux capacity.
AB  - The occurrence of pharmaceuticals, including antibacterial compounds, in the
      environment has been acknowledged as an emerging and troubling issue in
      environmental safety; their usage is constantly on the rise, and their effects on
      the environment are only partially understood. Such compounds can accumulate,
      contaminate the ecosystem, and contribute to the spreading of antibiotic
      resistance among bacteria, hindering human health. Bioluminescent Escherichia
      coli reporter strains, engineered to detect antibiotic compounds by fusing the
      promoter of the global regulator soxS to the Photorhabdus luminescens luxCDABE
      cassette, were further modified by altering their membrane permeability and
      efflux capabilities. This was accomplished by introducing several mutations in
      the efflux system (DeltaemrE, DeltaacrB, and DeltatolC) and by overexpressing
      OmpF, a porin located in the outer membrane that allows passive diffusion of
      molecules. Combinations of these alterations had a cumulative effect in lowering
      the detection threshold of several antibiotics, in some of the cases to
      concentrations reported from pharmaceutical-polluted environments. 

PMID- 23963274
TI  - Zinc supplementation in children and adolescents with acute leukemia.
AB  - BACKGROUND/OBJECTIVES: Zinc is known as an essential micronutrient for human
      health because of its structural and biochemical functions, influencing growth
      and affecting multiple aspects of the immune system. Zinc has been extensively
      studied in neoplastic processes but its role in children with leukemia still
      remains to be elucidated in several aspects. The aim of this study was to
      evaluate the effects of oral zinc supplementation on weight gain and infectious
      episodes in children and adolescents with acute leukemia. SUBJECTS/METHODS: This
      study included 38 patients, and was carried out as a randomized, double-blind,
      placebo-controlled investigation. The dosage of plasma zinc levels and the
      evaluation of nutritional status were performed during a period of 60 days. Zinc
      was supplemented orally, 2  mg/kg/day, in the form of amino acid salt. RESULTS:
      The results showed that plasma zinc concentrations did not increase significantly
      with the addition of the micronutrient. However, from a clinical point of view,
      it has become evident that supplementary zinc exerts a positive effect on
      nutritional status as positive weight gain. Moreover, the number of infection
      episodes was significantly reduced, possibly because of the immune stimuli.
      CONCLUSIONS: In conclusion, zinc supplementation can prevent some of the
      chemotherapy adverse effects in children with leukemia, improving their quality
      of life.

PMID- 23963275
TI  - Assessments of free carnitine levels in the plasma of patients who have undergone
      coronary artery bypass grafting.

PMID- 23963276
TI  - Predictors of the incident metabolic syndrome in healthy obese subjects: a decade
      of follow-up from the Tehran Lipid and Glucose Study.
AB  - BACKGROUND/OBJECTIVE: There is limited data from long-term prospective studies on
      the natural course of metabolic syndrome (MetS) incidence in healthy obese
      phenotypes. The aim of this study was to determine the incidence and predictors
      of the MetS in healthy obese subjects without the MetS at baseline after a decade
      of follow-up. SUBJECTS/METHODS: In this prospective cohort study, 438 obese
      subjects free from MetS at baseline, aged >=20 years, were selected from among
      the participants of the Tehran Lipid and Glucose Study and followed up for 10
      years for development of MetS. Based on national data, central obesity was
      defined as waist circumference cutoff point of 89 cm for men and 91 cm for women.
      RESULTS: Initially, subjects had a mean age of 41.1 +/- 11.8 years and a body
      mass index of 32.7 +/- 2.7 kg/m(2). At the end of follow-up, the cumulative
      incidence (95% confidence interval) of MetS was 44.0 (36.8-51.1)%. In the
      multivariable analysis, the adjusted odds ratios of hypertension,
      hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C) and
      insulin resistance for the development of MetS were 3.08 (1.39-6.79), 2.84 (1.26
      6.42), 6.49 (3.18-13.25) and 2.87 (1.55-5.32), respectively. The area under
      receiver operating characteristic curve of all the components was significantly
      higher than various combinations of MetS components, except for the two models
      including combinations of three components, that is, triglycerides (TGs), HDL-C
      and fasting blood sugar, as well as, TGs, HDL-C and systolic blood pressure.
      CONCLUSIONS: Our findings demonstrate that MetS developed in nearly half of the
      individuals during the 10 years of follow-up. Predictors of MetS in healthy obese
      subjects may differ from the general population, and waist circumference does not
      have an independent role.

PMID- 23963277
TI  - [Intensive care management of hematological and oncological patients].
AB  - Management of critically ill cancer patients warrants stringent admission
      criteria and clear concepts concerning duration and limits of intensive care.
      Recent developments in mechanical ventilation and sepsis therapy can easily be
      used to improve the outcome of critically ill cancer patients. The incidence and
      overall prognosis of cancer is constantly growing and, thus, the number of
      critically ill cancer patients is increasing. Furthermore, novel oncology drugs
      in particular immune modulators-produce unexpected and substantial side effects.
      Therefore, the development of an interdisciplinary algorithm by oncologists and
      intensivists remains an important and dynamic challenge. 

PMID- 23963278
TI  - [Statin therapy and cancer-related mortality].

PMID- 23963279
TI  - NHC to aNHC rearrangement by an organotin sulphide cation.
AB  - An intramolecularly P=O-coordinated dicationic diorganotin sulphide is presented.
      In solution, it shows a monomer-dimer equilibrium.

PMID- 23963280
TI  - Synthesis and properties of boron complexes of [14]triphyrins(2.1.1).
AB  - Boron complexes of [14]triphyrins(2.1.1) were prepared from free-base
      [14]triphyrins(2.1.1) with phenylboron dichloride. The absorption spectrum of the
      meso-free beta-alkyl-triphyrin boron complex in CH2Cl2 showed a broad weak band
      at around 640 nm assigned to transition from B-phenyl to the triphyrin, while
      that of the meso-aryl benzotriphyrin boron complex showed only Soret and Q bands.

PMID- 23963282
TI  - An approach to 8 stereoisomers of homonojirimycin from (D)-glucose via kinetic &
      thermodynamic azido-gamma-lactones.
AB  - Crystal structures were obtained for the two C2 epimeric azido-gamma-lactones 2
      azido-2-deoxy-3,5:6,7-di-O-isopropylidene-d-glycero-d-ido-heptono-1,4-lactone and
      2-azido-2-deoxy-3,5:6,7-di-O-isopropylidene-d-glycero-d-gulo-heptono-1,4-lactone
      prepared from kinetic and thermodynamic azide displacements of a triflate derived
      from d-glucoheptonolactone. Azido-gamma-lactones are very useful intermediates in
      the synthesis of iminosugars and polyhydroxylated amino acids. In this study two
      epimeric azido-heptitols allow biotechnological transformations via Izumoring
      techniques to 8 of the 16 possible homonojirimycin analogues, 5 of which were
      isolated pure because of the lack of stereoselectivity of the final reductive
      amination. A side-by-side glycosidase inhibition profile of 11 of the possible 16
      HNJ stereoisomers derived from d-glucose and d-mannose is presented. 

PMID- 23963283
TI  - Silibinin suppresses EMT-driven erlotinib resistance by reversing the high miR
      21/low miR-200c signature in vivo.
AB  - The flavolignan silibinin was studied for its ability to restore drug sensitivity
      to EGFR-mutant NSCLC xenografts with epithelial-to-mesenchymal transition (EMT)
      driven resistance to erlotinib. As a single agent, silibinin significantly
      decreased the tumor volumes of erlotinib-refractory NSCLC xenografts by
      approximately 50%. Furthermore, the complete abrogation of tumor growth was
      observed with the co-treatment of erlotinib and silibinin. Silibinin fully
      reversed the EMT-related high miR-21/low miR-200c microRNA signature and
      repressed the mesenchymal markers SNAIL, ZEB, and N-cadherin observed in
      erlotinib-refractory tumors. Silibinin was sufficient to fully activate a
      reciprocal mesenchymal-to-epithelial transition (MET) in erlotinib-refractory
      cells and prevent the highly migratogenic phenotype of erlotinib-resistant NSCLC
      cells. Given that the various mechanisms of resistance to erlotinib result from
      EMT, regardless of the EGFR mutation status, a water-soluble, silibinin-rich milk
      thistle extract might be a suitable candidate therapy for upcoming clinical
      trials aimed at preventing or reversing NSCLC progression following erlotinib
      treatment. 

PMID- 23963284
TI  - Participants, usage, and use patterns of a web-based intervention for the
      prevention of depression within a randomized controlled trial.
AB  - BACKGROUND: Although Web-based interventions have been shown to be effective,
      they are not widely implemented in regular care. Nonadherence (ie, participants
      not following the intervention protocol) is an issue. By studying the way Web
      based interventions are used and whether there are differences between adherers
      (ie, participants that started all 9 lessons) and nonadherers, more insight can
      be gained into the process of adherence. OBJECTIVE: The aims of this study were
      to (1) describe the characteristics of participants and investigate their
      relationship with adherence, (2) investigate the utilization of the different
      features of the intervention and possible differences between adherers and
      nonadherers, and (3) identify what use patterns emerge and whether there are
      differences between adherers and nonadherers. METHODS: Data were used from 206
      participants that used the Web-based intervention Living to the full, a Web-based
      intervention for the prevention of depression employing both a fully automated
      and human-supported format. Demographic and baseline characteristics of
      participants were collected by using an online survey. Log data were collected
      within the Web-based intervention itself. Both quantitative and qualitative
      analyses were performed. RESULTS: In all, 118 participants fully adhered to the
      intervention (ie, started all 9 lessons). Participants with an ethnicity other
      than Dutch were more often adherers (chi21=5.5, P=.02), and nonadherers used the
      Internet more hours per day on average (F1,203=3.918, P=.049). A logistic
      regression showed that being female (OR 2.02, 95% CI 1.01-4.04; P=.046) and
      having a higher need for cognition (OR 1.02; 95% CI 1.00-1.05; P=.02) increased
      the odds of adhering to the intervention. Overall, participants logged in an
      average of 4 times per lesson, but adherers logged in significantly more times
      per lesson than nonadherers (F1,204=20.710; P<.001). For use patterns, we saw
      that early nonadherers seemed to use fewer sessions and spend less time than late
      nonadherers and adherers, and fewer sessions to complete the lesson than
      adherers. Furthermore, late nonadherers seemed to have a shorter total duration
      of sessions than adherers. CONCLUSIONS: By using log data combined with baseline
      characteristics of participants, we extracted valuable lessons for redesign of
      this intervention and the design of Web-based interventions in general. First,
      although characteristics of respondents can significantly predict adherence,
      their predictive value is small. Second, it is important to design Web-based
      interventions to foster adherence and usage of all features in an intervention.
      TRIAL REGISTRATION: Dutch Trial Register Number: NTR3007;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3007 (Archived by
      WebCite at http://www.webcitation.org/6ILhI3rd8).

PMID- 23963285
TI  - Role of endothelial cell membrane transport in red wine polyphenols-induced
      coronary vasorelaxation: involvement of bilitranslocase.
AB  - Red wine polyphenols (RWP) induce nitric oxide (NO) and endothelium-derived
      hyperpolarization (EDH)-mediated coronary vasodilatation involving the redox
      sensitive PI3-kinase/Akt-dependent pathway in the endothelium. However, there is
      a gap of knowledge in explaining how bioactive polyphenols initialize their
      signalling pathway in endothelial cells. Here, we investigated the hypothesis
      that flavonoids act subsequently to their entry into the endothelium via the
      flavonoid membrane transporter bilitranslocase (TC 2.A.65.1.1). Thus, vascular
      reactivity studies were performed using isolated porcine coronary artery rings.
      We separately determined the NO- and EDH-mediated components of the relaxation in
      the presence of specific inhibitors. In either case, bilitranslocase antibodies
      significantly reduced the relaxations of coronary artery rings induced by RWP.
      Furthermore, bilitranslocase antibodies significantly reduced RWP-induced
      phosphorylation levels of Akt and eNOS, assessed in cultured endothelial cells
      from porcine coronary arteries by Western blot analysis. The present findings
      indicate that bilitranslocase-mediated membrane transport substantially
      contributes to the initial step of RWP-induced coronary vasodilatation. 

PMID- 23963287
TI  - Ex vivo method for high resolution imaging of cilia motility in rodent airway
      epithelia.
AB  - An ex vivo technique for imaging mouse airway epithelia for quantitative analysis
      of motile cilia function important for insight into mucociliary clearance
      function has been established. Freshly harvested mouse trachea is cut
      longitudinally through the trachealis muscle and mounted in a shallow walled
      chamber on a glass-bottomed dish. The trachea sample is positioned along its long
      axis to take advantage of the trachealis muscle to curl longitudinally. This
      allows imaging of ciliary motion in the profile view along the entire tracheal
      length. Videos at 200 frames/sec are obtained using differential interference
      contrast microscopy and a high speed digital camera to allow quantitative
      analysis of cilia beat frequency and ciliary waveform. With the addition of
      fluorescent beads during imaging, cilia generated fluid flow also can be
      determined. The protocol time spans approximately 30 min, with 5 min for chamber
      preparation, 5-10 min for sample mounting, and 10-15 min for videomicroscopy. 

PMID- 23963286
TI  - The antimelanoma activity of the histone deacetylase inhibitor panobinostat
      (LBH589) is mediated by direct tumor cytotoxicity and increased tumor
      immunogenicity.
AB  - Melanoma is the deadliest skin cancer, and its incidence has been increasing
      faster than any other cancer. Although immunogenic, melanoma is not effectively
      cleared by host immunity. In this study, we investigate the therapeutic,
      antimelanoma potential of the histone deacetylase inhibitor (HDACi) panobinostat
      (LBH589) by assessing both its cytotoxic effects on melanoma cells as well as
      enhancement of immune recognition of melanoma. Utilizing murine and human
      melanoma cell lines, we analyzed the effects of LBH589 on proliferation and
      survival. In addition, we analyzed the expression of several immunologically
      relevant surface markers and melanoma differentiation antigens, and the ability
      of LBH589-treated melanoma to activate antigen-specific T cells. Finally, we
      assessed the in-vivo effects of LBH589 in a mouse melanoma model. Low nanomolar
      concentrations of LBH589 inhibit the growth of all melanoma cell lines tested,
      but not normal melanocytes. This inhibition is characterized by increased
      apoptosis as well as a G1 cell cycle arrest. In addition, LBH589 augments the
      expression of major histocompatibility complex and costimulatory molecules on
      melanoma cells leading to an increased ability to activate antigen-specific T
      cells. Treatment also increases expression of melanoma differentiation antigens.
      In vivo, LBH589 treatment of melanoma-bearing mice results in a significant
      increase in survival. However, in immunodeficient mice, the therapeutic effect of
      LBH589 is lost. Taken together, LBH589 exerts a dual effect upon melanoma cells
      by affecting not only growth/survival but also by increasing melanoma
      immunogenicity. These effects provide the framework for future evaluation of this
      HDAC inhibitor in melanoma treatment. 

PMID- 23963288
TI  - Distinguishing Alzheimer's disease from normal pressure hydrocephalus: a search
      for MRI biomarkers.
AB  - Currently, no clinical or neuroradiological techniques have been validated to
      distinguish Alzheimer's disease (AD) from idiopathic normal pressure
      hydrocephalus (iNPH). Both share anatomical and clinical similarities: AD is a
      form of irreversible degenerative dementia, whereas the dementia manifested in
      iNPH is potentially "reversible" through various neurosurgical procedures. Hence,
      it is important to find specific imaging biomarkers that distinguish the two
      conditions. In addition, the ability to predict the response to neurosurgery in
      iNPH is something that has yet to be accomplished. In this systematic review, we
      describe and critically analyze the merits and drawbacks of the MR imaging
      parameters currently used to distinguish AD from iNPH and assess ways to predict
      the response after treatment of iNPH. We conclude that the combination of
      different neuroimaging sequences as well as quantitative and qualitative
      parameters could provide new insight for better diagnosis and treatment of these
      two different diseases. 

PMID- 23963289
TI  - Identification of three novel LRRK2 mutations associated with Parkinson's disease
      in a Calabrian population.
AB  - BACKGROUND: LRRK2 mutations are common in familial and sporadic Parkinson's
      disease (PD) cases. OBJECTIVE: We present a screening of the most frequently
      mutated exons of LRRK2 in Calabrian population. METHODS: Eighty-eight PD patients
      diagnosed according to standard criteria, underwent screening for LRRK2 mutations
      in exons 19, 21, 24, 25, 27, 29, 31, 32, 33, 35, 38, 40, 41, and 48. RESULTS:
      Eight LRRK2 variations were identified in nine patients affected by PD, including
      three novel missense variations (p.Phe1227Leu, p.Gly1520Ala, p.Ile2020Ser) and
      five previously identified mutations (p.Ala1151Thr, IVS31+3A>G, p.Arg1514Gln,
      p.Gly2019Ser, p.Thr2356Ile). LRRK2 frequency mutations were approximately 10.2%
      in all PD patients, 12% in familial, 8% in sporadic cases. The p.Gly2019Ser
      mutation was found in 2.3% of the total cohort and in 3.2% of sporadic cases. The
      clinical features of LRRK2-associated with PD in our patients were similar to
      those of idiopathic PD although most LRRK2 mutated patients presented with
      bradykinesia instead of tremor; 33.3% developed dementia. CONCLUSIONS: We
      identified three novel LRRK2 mutations and reported a higher frequency in
      Calabria compared to previously reported data possibly due to the relative
      genetic isolation of the Calabrian population. These findings contribute to the
      understanding of the role of LRKK2 variations in PD and provide additional
      genetic insight into this disease.

PMID- 23963290
TI  - Behavioral syndromes in mild cognitive impairment and Alzheimer's disease.
AB  - BACKGROUND: Behavioral disturbances belong to the core symptoms of dementia and
      are also common in mild cognitive impairment (MCI). The identification of sets of
      symptoms is clinically interesting, as interventions targeting syndromes may be
      more effective than the management of individual symptoms. OBJECTIVE: This study
      aimed to identify, describe, measure, and compare the fundamental behavioral
      syndromes that underlie the observed behavioral symptoms in MCI and Alzheimer's
      disease (AD). METHODS: A cross-sectional analysis of baseline data from a
      prospective, longitudinal study on behavioral symptoms in MCI and dementia was
      performed. The study population consisted of 270 MCI and 402 AD patients.
      Behavioral assessment was performed by means of Middelheim Frontality Score
      (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory (CMAI), and Cornell Scale
      for Depression in Dementia (CSDD). Principal components factor analysis with
      Direct Oblimin rotation was carried out on the MFS score >=5, seven cluster
      scores of the Behave-AD and the total scores of the CMAI and the CSDD. RESULTS:
      We identified three factors explaining behavior in the MCI group: a depression, a
      psychosis, and an agitation syndrome. Similar factors were found in AD, but the
      order: an agitation, a depression, and a psychosis syndrome, respectively, and
      the structure differed slightly. Diurnal rhythm disturbances and frontal lobe
      symptoms loaded with the depression syndrome in MCI and in AD they loaded with
      the agitation syndrome. Behavioral syndromes correlated in AD, but not in MCI,
      and the prevalence and severity of the behavioral syndromes were higher in AD
      than in MCI, except for the severity of the depression syndrome. CONCLUSION: In
      both MCI and AD, three similar behavioral syndromes exist, but behavior in MCI is
      more dominated by a depression syndrome, while behavior in AD is more subject to
      an agitation syndrome.

PMID- 23963291
TI  - Chromosome 19p in Alzheimer's disease: when genome meets transcriptome.
AB  - Genetic studies have identified several genomic loci including chr19p13.2
      relevant to Alzheimer's disease (AD) susceptibility. However, the functional
      roles of these genomic loci in AD pathogenesis require further clarification.
      Transcriptome as an endophenotype is critical for the understanding of disease
      mechanism. Here we demonstrate that chr19p is the most significantly perturbed
      chromosome region in AD brain transcriptome. With dual evidence from genome and
      transcriptome, chr19p likely play a special role in AD pathogenesis. 

PMID- 23963292
TI  - Effects of amnestic mild cognitive impairment on N2 and P3 Go/NoGo ERP
      components.
AB  - Although many studies have demonstrated decline in attention and executive
      function (especially in inhibitory control) in healthy aging and Alzheimer's
      disease (AD), similar studies concerning mild cognitive impairment (MCI) are
      scarce. In the present study, we evaluated how the cognitive decline associated
      with amnestic MCI (aMCI) affects these processes, analyzing the N2 and P3
      components of event-related potentials (ERPs) during the response (Go) and
      inhibition of response (NoGo) to different stimuli. ERPs were analyzed in 63
      healthy and 30 aMCI adults (aged 50 to 87 years) during performance of a Go/NoGo
      auditory-visual attention-distraction task. aMCI adults showed poorer execution
      (longer response times and fewer correct responses) and smaller Go-N2 and NoGo-N2
      amplitudes than control adults, whereas P3 amplitudes and N2 and P3 latencies did
      not differ between the groups. These results show that aMCI is associated with
      decline in executive function and stimuli evaluation in working memory. 

PMID- 23963293
TI  - Predicting progression to dementia in elderly subjects with mild cognitive
      impairment using both cognitive and neuroimaging predictors.
AB  - The objective of this work was to assess the predictive accuracy of targeted
      neuroimaging and neuropsychological measures for the detection of incipient
      dementia in individuals with mild cognitive impairment (MCI), and to examine the
      potential benefit of combining both classes of measures. Baseline MRI measures
      included hippocampal volume, cortical thickness, and white matter
      hyperintensities. Neuropsychological assessment focused on different aspects of
      episodic memory (i.e., familiarity, free recall, and associative memory) and
      executive control functions (i.e., working memory, switching, and planning).
      Global and regional cortical thinning was observed in MCI patients who progressed
      to dementia compared to those who remained stable, whereas no differences were
      found between groups for baseline hippocampal volume and white matter
      hyperintensities. The strongest neuroimaging predictors were baseline cortical
      thickness in the right anterior cingulate and middle frontal gyri. For cognitive
      predictors, we found that deficits in both free recall and recognition episodic
      memory tasks were highly suggestive of progression to dementia. Cortical thinning
      in the right anterior cingulate gyrus, combined to controlled and familiarity
      based retrieval deficits, achieved a classification accuracy of 87.5%, a
      specificity of 90.9%, and a sensitivity of 83.3%. This predictive model including
      both classes of measures provided more accurate predictions than those based on
      neuroimaging or cognitive measures alone. Overall, our findings suggest that
      detecting preclinical Alzheimer's disease is probably best accomplished by
      combining complementary information from targeted neuroimaging and cognitive
      classifiers, and highlight the importance of taking into account both structural
      and functional changes associated with the disease. 

PMID- 23963294
TI  - The dual role of Zn-acid medium for one-step rapid synthesis of M@rGO (M = Au,
      Pt, Pd and Ag) hybrid nanostructures at room temperature.
AB  - We report a new protocol for the synthesis of M@rGO (M = Au, Pt, Pd, Ag and rGO =
      reduced graphene oxide) hybrid nanostructures at room temperature in Zn-acid
      medium. The roles of Zn-acid are to reduce the GO by generated hydrogen and the
      deposition of metal nanoparticles on rGO by galvanic replacement reaction between
      Zn and M(n+).

PMID- 23963295
TI  - Twins in spirit: DOTATATE and high-affinity DOTATATE.

PMID- 23963296
TI  - Clinical applications of SPECT/CT in imaging the extremities.
AB  - Today, SPECT/CT is increasingly used and available in the majority of larger
      nuclear medicine departments. Several applications of SPECT/CT as a supplement to
      or replacement for traditional conventional bone scintigraphy have been
      established in recent years. SPECT/CT of the upper and lower extremities is
      valuable in many conditions with abnormal bone turnover due to trauma,
      inflammation, infection, degeneration or tumour. SPECT/CT is often used in
      patients if conventional radiographs are insufficient, if MR image quality is
      impaired due to metal implants or in patients with contraindications to MR. In
      complex joints such as those in the foot and wrist, SPECT/CT provides exact
      anatomical correlation of pathological uptake. In many cases SPECT increases the
      sensitivity and CT the specificity of the study, increasing confidence in the
      final diagnosis compared to planar images alone. The CT protocol should be
      adapted to the clinical question and may vary from very low-dose (e.g.
      attenuation correction only), to low-dose for anatomical correlation, to normal
      dose protocols enabling precise anatomical resolution. The aim of this review is
      to give an overview of SPECT/CT imaging of the extremities with a focus on the
      hand and wrist, knee and foot, and for evaluation of patients after joint
      arthroplasty. 

PMID- 23963298
TI  - Clinical utility gene card for: choroideremia.

PMID- 23963297
TI  - Clinical and biochemical features guiding the diagnostics in neurometabolic cutis
      laxa.
AB  - Patients with cutis laxa (CL) have wrinkled, sagging skin with decreased
      elasticity. Skin symptoms are associated with variable systemic involvement. The
      most common, genetically highly heterogeneous form of autosomal recessive CL,
      ARCL2, is frequently associated with variable metabolic and neurological
      symptoms. Progeroid symptoms, dysmorphic features, hypotonia and psychomotor
      retardation are highly overlapping in the early phase of these disorders. This
      makes the genetic diagnosis often challenging. In search for discriminatory
      symptoms, we prospectively evaluated clinical, neurologic, metabolic and genetic
      features in our patient cohort referred for suspected ARCL. From a cohort of 26
      children, we confirmed mutations in genes associated with ARCL in 16 children (14
      probands), including 12 novel mutations. Abnormal glycosylation and gyration
      abnormalities were mostly, but not always associated with ATP6V0A2 mutations.
      Epilepsy was most common in ATP6V0A2 defects. Corpus callosum dysgenesis was
      associated with PYCR1 and ALDH18A1 mutations. Dystonic posturing was
      discriminatory for PYCR1 and ALDH18A1 defects. Metabolic markers of mitochondrial
      dysfunction were found in one patient with PYCR1 mutations. So far unreported
      white matter abnormalities were found associated with GORAB and RIN2 mutations.
      We describe a large cohort of CL patients with neurologic involvement. Migration
      defects and corpus callosum hypoplasia were not always diagnostic for a specific
      genetic defect in CL. All patients with ATP6V0A2 defects had abnormal
      glycosylation. To conclude, central nervous system and metabolic abnormalities
      were discriminatory in this genetically heterogeneous group, although not always
      diagnostic for a certain genetic defect in CL. 

PMID- 23963299
TI  - Targeted next-generation sequencing reveals further genetic heterogeneity in
      axonal Charcot-Marie-Tooth neuropathy and a mutation in HSPB1.
AB  - Charcot-Marie-Tooth disease (CMT) is a group of hereditary peripheral
      neuropathies. The dominantly inherited axonal CMT2 displays striking genetic
      heterogeneity, with 17 presently known disease genes. The large number of
      candidate genes, combined with lack of genotype-phenotype correlations, has made
      genetic diagnosis in CMT2 time-consuming and costly. In Finland, 25% of dominant
      CMT2 is explained by either a GDAP1 founder mutation or private MFN2 mutations
      but the rest of the families have remained without molecular diagnosis. Whole
      exome and genome sequencing are powerful techniques to find disease mutations for
      CMT patients but they require large amounts of sequencing to confidently exclude
      heterozygous variants in all candidate genes, and they generate a vast amount of
      irrelevant data for diagnostic needs. Here we tested a targeted next-generation
      sequencing approach to screen the CMT2 genes. In total, 15 unrelated patients
      from dominant CMT2 families from Finland, in whom MFN2 and GDAP1 mutations had
      been excluded, participated in the study. The targeted approach produced
      sufficient sequence coverage for 95% of the 309 targeted exons, the rest we
      excluded by Sanger sequencing. Unexpectedly, the screen revealed a disease
      mutation only in one family, in the HSPB1 gene. Thus, new disease genes underlie
      CMT2 in the remaining families, indicating further genetic heterogeneity. We
      conclude that targeted next-generation sequencing is an efficient tool for
      genetic screening in CMT2 that also aids in the selection of patients for genome
      wide approaches. 

PMID- 23963301
TI  - Flexible electrostatic nanogenerator using graphene oxide film.
AB  - Recently, graphene oxide (GO) super capacitors with ultra-high energy densities
      have received significant attention. In addition to their use in energy storage,
      GO capacitors might also have broad applications in renewable energy engineering,
      such as energy harvesting. Here, a flexible nanogenerator based on GO film is
      designed. A multilayer structure Al/PI/GO/PI/ITO is made on a flexible PET
      substrate. The GO nanogenerator could generate a peak voltage of 2 V with a
      current of 30 nA upon the repetitive application of a 15 N force with a frequency
      of 1 Hz. Moreover, the output voltage was increased to 34.4 V upon increasing the
      frequency of force application to 10 Hz. Compared with control samples, embedding
      GO film with a release structure into the device could significantly enhance the
      output voltage from 0.1 V to 2.0 V. The mechanism of our nanogenerator can be
      explained by an electrostatic effect, which is fundamentally different from that
      of previously reported piezoelectric and triboelectric generators. In this
      manuscript, we demonstrate flexible nanogenerators with large-area graphene based
      materials, which may open up new avenues of research with regard to applications
      in energy harvesting. 

PMID- 23963300
TI  - Deletions involving genes WHSC1 and LETM1 may be necessary, but are not
      sufficient to cause Wolf-Hirschhorn Syndrome.
AB  - Wolf-Hirschhorn syndrome (WHS) is a complex genetic disorder caused by the loss
      of genomic material from the short arm of chromosome 4. Genotype-phenotype
      correlation studies indicated that the loss of genes within 4p16.3 is necessary
      for expression of the core features of the phenotype. Within this region,
      haploinsufficiency of the genes WHSC1 and LETM1 is thought to be a major
      contributor to the pathogenesis of WHS. We present clinical findings for three
      patients with relatively small (<400 kb) de novo interstitial deletions that
      overlap WHSC1 and LETM1. 3D facial analysis was performed for two of these
      patients. Based on our findings, we propose that hemizygosity of WHSC1 and LETM1
      is associated with a clinical phenotype characterized by growth deficiency,
      feeding difficulties, and motor and speech delays. The deletion of additional
      genes nearby WHSC1 and LETM1 does not result in a marked increase in the severity
      of clinical features, arguing against their haploinsufficiency. The absence of
      seizures and typical WHS craniofacial findings in our cohort suggest that
      deletion of distinct or additional 4p16.3 genes is necessary for expression of
      these features. Altogether, these results show that although loss-of-function for
      WHSC1 and/or LETM1 contributes to some of the features of WHS, deletion of
      additional genes is required for the full expression of the phenotype, providing
      further support that WHS is a contiguous gene deletion disorder. 

PMID- 23963302
TI  - Catecholamine norepinephrine diminishes lung epithelial cell adhesion of
      Streptococcus pneumoniae by binding iron.
AB  - Systemic release of norepinephrine (NE) is a component of the acute host response
      to infection, and studies in the field of microbial endocrinology indicate
      generally that NE increases the bacterial growth rate and promotes invasive
      disease. However, NE attenuates experimental invasive pneumococcal disease. We
      determined that NE promoted pneumococcal growth but paradoxically decreased
      pneumococcal adhesion to host cells. This effect was independent of the classical
      adhesin CbpA. Microarray analysis indicated that the effect of NE involved two
      two-component regulatory systems that both regulate expression of the Piu iron
      uptake ABC transport operon. We propose that NE, a known siderophore, enhances
      iron availability to the bacteria, resulting in greater bacterial replication and
      decreased expression of Piu operon products. Downregulation of the operon
      includes decreased expression of the Piu-associated adhesin PiuD. Our results
      suggested that the iron-dependent inhibitory effect of NE on pneumococcal
      adherence is a mechanism underlying the amelioration of pneumococcal disease by
      NE. 

PMID- 23963303
TI  - Manipulation of the tyrothricin production profile of Bacillus aneurinolyticus.
AB  - A group of non-ribosomally produced antimicrobial peptides, the tyrocidines from
      the tyrothricin complex, have potential as antimicrobial agents in both medicine
      and industry. Previous work by our group illustrated that the more polar
      tyrocidines rich in Trp residues in their structure were more active toward Gram
      positive bacteria, while the more non-polar tyrocidines rich in Phe residues had
      greater activity toward Plasmodium falciparum, one of the major causative
      pathogens of malaria in humans. Our group also found that the tyrocidines have
      pronounced antifungal activity, dictated by the primary sequence of the
      tyrocidine. By simply manipulating the Phe or Trp concentration in the culture
      medium of the tyrothricin producer, Bacillus aneurinolyticus ATCC 10068, we were
      able to modulate the production of subsets of tyrocidines, thereby tailoring the
      tyrothricin complex to target specific pathogens. We optimized the tailored
      tyrothricin production using a novel, small-scale, high-throughput deep 96-well
      plate culturing method followed by analyses of the peptide mixtures using ultra
      performance liquid chromatography linked to mass spectrometry. We were able to
      gradually shift the production profile of the tyrocidines and analogues, as well
      as the gramicidins between two extremes in terms of peptide subsets and peptide
      hydrophobicity. This study demonstrated that tyrothricin peptide subsets with
      targeted activity can be efficiently produced by simple manipulation of the
      aromatic amino acid profile of the culture medium. 

PMID- 23963304
TI  - Cardiovascular diseases and the work environment.

PMID- 23963305
TI  - Nature of hardness evolution in nanocrystalline NiTi shape memory alloys during
      solid-state phase transition.
AB  - Due to a distinct nature of thermomechanical smart materials' reaction to applied
      loads, a revolutionary approach is needed to measure the hardness and to
      understand its size effect for pseudoelastic NiTi shape memory alloys (SMAs)
      during the solid-state phase transition. Spherical hardness is increased with
      depths during the phase transition in NiTi SMAs. This behaviour is contrary to
      the decrease in the hardness of NiTi SMAs with depths using sharp tips and the
      depth-insensitive hardness of traditional metallic alloys using spherical tips.
      In contrast with the common dislocation theory for the hardness measurement, the
      nature of NiTi SMAs' hardness is explained by the balance between the interface
      and the bulk energy of phase transformed SMAs. Contrary to the energy balance in
      the indentation zone using sharp tips, the interface energy was numerically shown
      to be less dominant than the bulk energy of the phase transition zone using
      spherical tips. 

PMID- 23963306
TI  - Effects of mobile augmented reality learning compared to textbook learning on
      medical students: randomized controlled pilot study.
AB  - BACKGROUND: By adding new levels of experience, mobile Augmented Reality (mAR)
      can significantly increase the attractiveness of mobile learning applications in
      medical education. OBJECTIVE: To compare the impact of the heightened realism of
      a self-developed mAR blended learning environment (mARble) on learners to
      textbook material, especially for ethically sensitive subjects such as forensic
      medicine, while taking into account basic psychological aspects (usability and
      higher level of emotional involvement) as well as learning outcomes (increased
      learning efficiency). METHODS: A prestudy was conducted based on a convenience
      sample of 10 third-year medical students. The initial emotional status was
      captured using the "Profile of Mood States" questionnaire (POMS, German
      variation); previous knowledge about forensic medicine was determined using a 10
      item single-choice (SC) test. During the 30-minute learning period, the students
      were randomized into two groups: the first group consisted of pairs of students,
      each equipped with one iPhone with a preinstalled copy of mARble, while the
      second group was provided with textbook material. Subsequently, both groups were
      asked to once again complete the POMS questionnaire and SC test to measure
      changes in emotional state and knowledge gain. Usability as well as pragmatic and
      hedonic qualities of the learning material was captured using AttrakDiff2
      questionnaires. Data evaluation was conducted anonymously. Descriptive statistics
      for the score in total and the subgroups were calculated before and after the
      intervention. The scores of both groups were tested against each other using
      paired and unpaired signed-rank tests. An item analysis was performed for the SC
      test to objectify difficulty and selectivity. RESULTS: Statistically significant,
      the mARble group (6/10) showed greater knowledge gain than the control group
      (4/10) (Wilcoxon z=2.232, P=.03). The item analysis of the SC test showed a
      difficulty of P=0.768 (s=0.09) and a selectivity of RPB=0.2. For mARble, fatigue
      (z=2.214, P=.03) and numbness (z=2.07, P=.04) decreased with statistical
      significance when comparing pre- and post-tests. Vigor rose slightly, while
      irritability did not increase significantly. Changes in the control group were
      insignificant. Regarding hedonic quality (identification, stimulation,
      attractiveness), there were significant differences between mARble (mean 1.179,
      CI -0.440 to 0.440) and the book chapter (mean -0.982, CI -0.959 to 0.959); the
      pragmatic quality mean only differed slightly. CONCLUSIONS: The mARble group
      performed considerably better regarding learning efficiency; there are hints for
      activating components of the mAR concept that may serve to fascinate the
      participants and possibly boost interest in the topic for the remainder of the
      class. While the small sample size reduces our study's conclusiveness, its design
      seems appropriate for determining the effects of interactive eLearning material
      with respect to emotions, learning efficiency, and hedonic and pragmatic
      qualities using a larger group. TRIAL REGISTRATION: German Clinical Trial
      Register (DRKS), DRKS-ID: DRKS00004685; https://drks-neu.uniklinik
      freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004685.

PMID- 23963307
TI  - A randomized, double-blind, placebo-controlled study of the lowest effective dose
      of drospirenone with 17beta-estradiol for moderate to severe vasomotor symptoms
      in postmenopausal women.
AB  - OBJECTIVE: This study aims to investigate the efficacy and safety of daily
      drospirenone/17beta-estradiol in two low-dose combinations (0.25 mg/0.5 mg and
      0.5 mg/0.5 mg, respectively) versus 17beta-estradiol (0.3 mg) or placebo in
      postmenopausal women with moderate to severe vasomotor symptoms. METHODS: Seven
      hundred thirty-five postmenopausal women aged 40 years or older who experienced a
      minimum of 7 to 8 moderate to severe hot flushes per day, or 50 to 60 moderate to
      severe hot flushes per week, participated in a 12-week, double-blind, randomized,
      placebo-controlled study. The primary efficacy variables were mean changes from
      baseline to weeks 4 and 12 in the weekly frequency and weekly mean daily severity
      of moderate to severe hot flushes recorded daily by the participants on diary
      cards. RESULTS: All active treatments were significantly more effective than
      placebo for the primary efficacy variables for drospirenone/17beta-estradiol (P <
      0.0001), and for 17beta-estradiol (P < 0.01) at 4 and 12 weeks. Efficacy was
      greater for both low-dose drospirenone/17beta-estradiol combinations versus the
      lower-dose 17beta-estradiol. Change in vaginal pH and vaginal maturation index
      showed significant improvements (with P values versus placebo of <0.0001 and P <=
      0.0028, respectively), and exploratory analysis of the Clinical Global
      Impressions scale score indicated an overall satisfaction of women with active
      treatments. All active treatments were generally well tolerated with low rates of
      adverse event-related dropouts, and the safety profile of drospirenone/17beta
      estradiol in both low-dose combinations was consistent with previous studies.
      CONCLUSIONS: Drospirenone 0.25 mg/17beta-estradiol 0.5 mg is concluded to be the
      lowest dose with demonstrated efficacy in the treatment of postmenopausal women
      with moderate to severe vasomotor symptoms.

PMID- 23963308
TI  - Urinary incontinence: still waiting for a champion.

PMID- 23963309
TI  - Population pharmacokinetic/pharmacodynamic evaluation of low-dose drospirenone
      with 17beta-estradiol in postmenopausal women with moderate to severe vasomotor
      symptoms.
AB  - OBJECTIVE: This study aims to characterize the pharmacokinetics/pharmacodynamics
      of drospirenone and estradiol in the treatment of postmenopausal women with
      moderate to severe vasomotor symptoms and to explore the relationship between the
      serum exposures of estradiol and drospirenone and efficacy, measured by
      reductions in moderate to severe hot flushes. METHODS: Participants in a 12-week,
      double-blind, randomized, placebo-controlled study of daily
      drospirenone/estradiol in two low-dose combinations (0.25 mg/0.5 mg and 0.5
      mg/0.5 mg), estradiol (0.3 mg), or placebo provided infrequent serum samples for
      pharmacokinetic analysis of estradiol and drospirenone, with additional frequent
      sampling during 24 hours in a study subset. RESULTS: Estradiol steady-state serum
      concentrations were described by a one-compartmental model with first-order
      elimination and zero-order absorption. The pharmacokinetics of drospirenone was
      described by a linear open two-compartment model with first-order elimination
      kinetics from the central compartment and delayed first-order absorption
      kinetics. A total of 1,516 serum estradiol concentrations and 736 serum
      drospirenone concentrations (n = 251) from 383 women were evaluated. Baseline
      estradiol concentrations increased with rising body mass index, and apparent
      clearance of estradiol at steady state was 39% higher in smokers versus
      nonsmokers. The serum exposures of both estradiol and drospirenone affected
      efficacy, as analyzed by a generalized linear model. Smoking had a negative
      effect on the efficacy of hormone therapy. CONCLUSIONS: The efficacy of low-dose
      drospirenone/estradiol for reducing vasomotor symptoms correlates with the serum
      exposure of estradiol and, for the first time, the serum exposure of
      drospirenone. Smoking adversely affects the clearance of estradiol and the
      efficacy of treatment.

PMID- 23963310
TI  - Utility of obesity indices in screening Chinese postmenopausal women for
      metabolic syndrome.
AB  - OBJECTIVE: Although a variety of indices have been used to assess obesity, which
      is closely associated with the development of metabolic syndrome (MetS), the best
      indicator of the effects of fat accumulation on Chinese postmenopausal women is
      still uncertain. Thus, the objectives of this study were to analyze the potential
      of different obesity indices and to explore which index is best for predicting
      MetS in Chinese postmenopausal women. METHODS: A cross-sectional analysis of the
      baseline data of 1,234 Chinese postmenopausal women (aged 42-79 y) who
      participated in the annual health checkup was performed. The obesity indices of
      all participants, including body mass index (BMI), waist circumference (WC),
      waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), percent body fat (PBF),
      and fat mass index (FMI), were measured or calculated. The updated National
      Cholesterol Education Program/Adult Treatment Panel III criteria were used to
      assess MetS risk factors. Spearman and partial correlations were used to assess
      correlations between obesity indices and MetS components. The area under the
      curve of the receiver operating characteristic (ROC) curve was used to determine
      the optimal cutoff values of all indicators of MetS development. The values of
      BMI, WC, WHR, WHtR, PBF, and FMI that resulted in the maximization of the Youden
      index (sensitivity + specificity - 1) were defined as optimal. RESULTS: Among the
      participants, 38.8% (n = 479) were identified as having two or more nonadipose
      MetS risk components (excluding a positive WC component). These women had higher
      obesity indices than women with fewer metabolic risk factors. All indices were
      significantly associated with all MetS components even after controlling for age
      and C-reactive protein. A BMI of 24.0 kg/m, a WHR of 0.85, a WC of 79.9 cm, a
      WHtR of 0.49, a PBF of 29.9%, and an FMI of 7.2 kg/m were the optimal cutoff
      values for predicting at least two other MetS components according to ROC curve
      analysis. However, among the indicators of central obesity, WHR and WHtR showed
      the greatest area under the ROC curve. CONCLUSIONS: WHR and WHtR are the best
      indicators of MetS development. A WHR of 0.85 or higher and a WHtR of 0.49 or
      higher should be incorporated into the identification of MetS risk in Chinese
      postmenopausal women.

PMID- 23963312
TI  - An optical deoxyribonucleic acid-based half-subtractor.
AB  - This study introduces an optical DNA-based logic circuit that mimics a half
      subtractor. The system contains an Au-surface immobilized molecular-beacon
      molecule that serves as a dual-gate molecule and outputs two series of
      fluorescence signals following Boolean INH and XOR patterns after interacting
      with one or two single-stranded DNA molecules as input. To the best of our
      knowledge, the system reported herein is rather concise compared to other
      molecular logic gate systems. 

PMID- 23963311
TI  - Creating dynamic images of short-lived dopamine fluctuations with lp-ntPET:
      dopamine movies of cigarette smoking.
AB  - We describe experimental and statistical steps for creating dopamine movies of
      the brain from dynamic PET data. The movies represent minute-to-minute
      fluctuations of dopamine induced by smoking a cigarette. The smoker is imaged
      during a natural smoking experience while other possible confounding effects
      (such as head motion, expectation, novelty, or aversion to smoking repeatedly)
      are minimized. We present the details of our unique analysis. Conventional
      methods for PET analysis estimate time-invariant kinetic model parameters which
      cannot capture short-term fluctuations in neurotransmitter release. Our analysis-
      yielding a dopamine movie--is based on our work with kinetic models and other
      decomposition techniques that allow for time-varying parameters. This aspect of
      the analysis--temporal-variation--is key to our work. Because our model is also
      linear in parameters, it is practical, computationally, to apply at the voxel
      level. The analysis technique is comprised of five main steps: pre-processing,
      modeling, statistical comparison, masking and visualization. Preprocessing is
      applied to the PET data with a unique 'HYPR' spatial filter that reduces spatial
      noise but preserves critical temporal information. Modeling identifies the time
      varying function that best describes the dopamine effect on 11C-raclopride
      uptake. The statistical step compares the fit of our (lp-ntPET) model to a
      conventional model. Masking restricts treatment to those voxels best described by
      the new model. Visualization maps the dopamine function at each voxel to a color
      scale and produces a dopamine movie. Interim results and sample dopamine movies
      of cigarette smoking are presented.

PMID- 23963313
TI  - Bacterial second messengers, cGMP and c-di-GMP, in a quest for regulatory
      dominance.

PMID- 23963314
TI  - The SAMHD1 knockout mouse model: in vivo veritas?

PMID- 23963315
TI  - Unaltered lactate and glucose transporter levels in the MPTP mouse model of
      Parkinson's disease.
AB  - BACKGROUND: Metabolic impairment contributes to development of Parkinson's
      disease (PD). Mitochondrial dysfunction is involved in degeneration of nigral
      dopamine neurons. Also, in PD there are alterations in glucose metabolism in
      nigro-striatal pathways, and increased cerebral lactate levels have been found.
      OBJECTIVES: We raise the question of whether changes in the amount transporters
      of energy substrates are involved in the pathogenesis of PD. METHODS: We have
      used confocal immunofluorescence and immunogold postembedding electron
      microscopic techniques to study whether there are altered levels of the
      transporters for monocarboxylates (MCT1 and MCT2) and glucose (GLUT1) in the MPTP
      mouse model of PD. RESULTS: We found that MCT1 and GLUT1 were densely located in
      blood vessel endothelium, while MCT2 was present in perivascular astrocytic end
      feet processes in the substantia nigra and the striatum of control mice. We found
      that the localisation and densities of MCTs and GLUT1 were unaltered in the PD
      model. DISCUSSION: This is the first study reporting on the distribution of
      metabolic transporters in PD. Our results suggest that, although there are
      metabolic impairments in PD, the levels of MCT1, MCT2 and GLUT1 is not changed
      following dopaminergic neurodegeneration. This is in contrast to findings in
      other neurodegenerative disease, such as mesial temporal lobe epilepsy, where
      there are large alterations in MCT levels.

PMID- 23963316
TI  - Relationship between cognitive dysfunction and behavioural symptoms in Nigerian
      patients with Parkinson's disease no dementia.
AB  - BACKGROUND: There is presently no information on the behavioural symptoms that
      are related to cognitive dysfunction in African patients with Parkinson's
      disease. OBJECTIVES: This study highlights the behavioral symptoms that are
      related to global cognitive dysfunction without dementia, as well as the
      caregivers' distress they create in a population of Nigerians with idiopathic
      Parkinson's disease. METHODS: Fifty patients with idiopathic Parkinson's disease,
      confirmed using the United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank
      Clinical Diagnostic Criteria, were cross-sectionally assessed for cognitive
      functions using the modified Mini-mental State Examination (MMSE), motor symptoms
      using the Unified Parkinson's disease Rating Scale (UPDRS), as well as
      neuropsychiatric symptoms and caregivers' distress using the Neuropsychiatric
      Inventory (NPI). Additional information obtained from all the participants and
      their caregivers included demographic data, personal history, psychiatric
      history, medical history and family history. The behavioural, caregivers'
      distress and motor correlates of cognitive dysfunction were explored. RESULTS: In
      all, 24.0% of the patients had cognitive dysfunction according to the local norm
      of the MMSE. Hallucinations (Chi2 = 5.556, p = 0.018) and agitation (Chi2 =
      5.556, p = 0.018) were related to cognitive dysfunctions. There was more
      behaviour related caregivers' distress in those with cognitive dysfunction than
      those without (Chi2 = 2.208, p = 0.032). The MMSE scores correlated inversely
      with the score for rigidity (r = -0.506, p = 0.0002), bradykinesia (r = -0.592, p
      < 0.0001), and the UPDRS total score (r = -0.503, p = 0.0002). CONCLUSION: The
      psychotic symptoms of hallucinations and agitations differentiated Parkinson's
      disease patients with cognitive dysfunction from those with normal cognition.
      Generally, the presence of behavioural symptom led to more distress in the
      caregivers of patients with cognitive dysfunction.

PMID- 23963317
TI  - Effects of London dispersion correction in density functional theory on the
      structures of organic molecules in the gas phase.
AB  - A benchmark set of 25 rotational constants measured in the gas phase for nine
      molecules (termed ROT25) was compiled from available experimental data. The
      medium-sized molecules with 18-35 atoms cover common (bio)organic structure
      motifs including hydrogen bonding and flexible side chains. They were each
      considered in a single conformation. The experimental B0 values were back
      corrected to reference equilibrium rotational constants (Be) by computation of
      the vibrational corrections DeltaBvib. Various density functional theory (DFT)
      methods and Hartree-Fock with and without dispersion corrections as well as MP2
      type methods and semi-empirical quantum chemical approaches are investigated. The
      ROT25 benchmark tests their ability to describe covalent bond lengths, longer
      inter-atomic distances, and the relative orientation of functional groups
      (intramolecular non-covalent interactions). In general, dispersion corrections to
      DFT and HF increase Be values (shrink molecular size) significantly by about 0.5
      1.5% thereby in general improving agreement with the reference data. Regarding
      DFT methods, the overall accuracy of the optimized structures roughly follows the
      'Jacobs ladder' classification scheme, i.e., it decreases in the series double
      hybrid > (meta)hybrid > (meta)GGA > LDA. With B2PLYP-D3, SCS-MP2, B3LYP-D3/NL, or
      PW6B95-D3 methods and extended QZVP (def2-TZVP) AO basis sets, Be values,
      accurate to about 0.3-0.6 (0.5-1)% on average, can be computed routinely. The
      accuracy of B2PLYP-D3/QZVP with a mean deviation of only 3 MHz and a standard
      deviation of 0.24% is exceptional and we recommend this method when highly
      accurate structures are required or for problematic conformer assignments. The
      correlation effects for three inter-atomic distance regimes (covalent, medium
      range, long) and the performance of minimal basis set (semi-empirical) methods
      are discussed. 

PMID- 23963318
TI  - On the distribution of DNA translocation times in solid-state nanopores: an
      analysis using Schrodinger's first-passage-time theory.
AB  - In this short paper, a correction is made to the recently proposed solution of Li
      and Talaga to a 1D biased diffusion model for linear DNA translocation, and a new
      analysis will be given to their data. It was pointed out by us recently that this
      1D linear translocation model is equivalent to the one that was considered by
      Schrodinger for the Ehrenhaft-Millikan measurements on electron charge. Here, we
      apply Schrodinger's first-passage-time distribution formula to the data set in Li
      and Talaga. It is found that Schrodinger's formula can be used to describe the
      time distribution of DNA translocation in solid-state nanopores. These fittings
      yield two useful parameters: the drift velocity of DNA translocation and the
      diffusion constant of DNA inside the nanopore. The results suggest two regimes of
      DNA translocation: (I) at low voltages, there are clear deviations from
      Smoluchowski's linear law of electrophoresis, which we attribute to the entropic
      barrier effects; (II) at high voltages, the translocation velocity is a linear
      function of the applied electric field. In regime II, the apparent diffusion
      constant exhibits a quadratic dependence on the applied electric field,
      suggesting a mechanism of Taylor-dispersion effect likely due the electro-osmotic
      flow field in the nanopore channel. This analysis yields a dispersion-free
      diffusion constant value of 11.2 nm2 us-1 for the segment of DNA inside the
      nanopore, which is in quantitative agreement with the Stokes-Einstein theory. The
      implication of Schrodinger's formula for DNA sequencing is discussed.

PMID- 23963319
TI  - Deep tissue optical imaging of upconverting nanoparticles enabled by exploiting
      higher intrinsic quantum yield through use of millisecond single pulse excitation
      with high peak power.
AB  - We have accomplished deep tissue optical imaging of upconverting nanoparticles at
      800 nm, using millisecond single pulse excitation with high peak power. This is
      achieved by carefully choosing the pulse parameters, derived from time-resolved
      rate-equation analysis, which result in higher intrinsic quantum yield that is
      utilized by upconverting nanoparticles for generating this near infrared
      upconversion emission. The pulsed excitation approach thus promises previously
      unreachable imaging depths and shorter data acquisition times compared with
      continuous wave excitation, while simultaneously keeping the possible thermal
      side-effects of the excitation light moderate. These key results facilitate means
      to break through the general shallow depth limit of upconverting-nanoparticle
      based fluorescence techniques, necessary for a range of biomedical applications,
      including diffuse optical imaging, photodynamic therapy and remote activation of
      biomolecules in deep tissues. 

PMID- 23963320
TI  - Trabecular metalTM shoulder prosthesis in the treatment of complex proximal
      humeral fractures.
AB  - PURPOSE: Shoulder arthroplasty is one of the options for the treatment of complex
      proximal humeral fractures. The purpose of this study was to assess the clinical
      and radiographic results of the trabecular metal shoulder prosthesis in the
      treatment of complex proximal humeral fractures. METHODS: Fifty-one consecutive
      patients with complex proximal humeral fractures who underwent primary shoulder
      arthroplasties with the trabecular metalTM prosthesis were enrolled in this
      study. At the final follow-up appointment, 42 of the patients (82.4% of the total
      patients enrolled) were available for both clinical and radiographic evaluation.
      There were 28 women and 14 men with a mean age of 65.4 +/- 10.7 years. The
      dominant arm was involved in 30 of the cases. According to Neer's classification,
      there were seven three-part fractures, 27 four-part fractures and eight head
      splitting fractures. Additionally, there were 37 hemiarthroplasties and five
      total shoulder arthroplasties. RESULTS: After a mean follow-up of 37.0 +/- 8.4
      months (range 24-52 months), the average ranges of motion were: 38.6 +/- 15.0
      degrees  for external rotation, L3 level for internal rotation and 132.3 +/- 36.0
      degrees  for forward elevation. The mean American Shoulder and Elbow Surgeons,
      visual analogue scale and University of California, Los Angeles scores were 82.1
      +/- 14.1, 0.4 +/- 1.1 and 28.8 +/- 5.1, respectively. The post-operative
      radiographs exhibited an anatomically attached greater tuberosity in 39 of the 42
      shoulders. Of the three patients with greater tuberosity complications, as
      displayed by their radiographs, two were observed with malpositioned
      tuberosities, while the other greater tuberosity was resorbed. Proximal migration
      of the prosthesis was observed in all three shoulders with greater tuberosity
      complications and in two shoulders with an anatomically attached greater
      tuberosity. No neurovascular injury, infection or prosthetic loosening was
      identified during the final follow-up appointments. CONCLUSIONS: Satisfactory
      results can be expected with the trabecular metal shoulder prosthesis for the
      treatment of complex proximal humeral fractures. The post-operative radiographs
      demonstrated an anatomically healed greater tuberosity in 93 % of the patients at
      a minimum follow-up time of two years.

PMID- 23963321
TI  - Issues in interstudy comparisons of bone microarchitecture.

PMID- 23963322
TI  - [Device related infections. How to identify and how to treat].
AB  - Because of the enormous increase in pacemaker and implantable cardioverter
      defibrillator (ICD) implants, the number of device-related infections has also
      increased considerably. In fact, this increase has been out of proportion due to
      the higher patient age at implant, the increased co-morbidity of patients and the
      higher complexity of the implanted devices. Apart from few exceptions the
      infection of a pacemaker or ICD requires complete explantation of the whole
      system with adjunctive antibiotic therapy. The diagnosis of device infection, the
      indication and different options for therapy are thoroughly discussed in this
      article according to the current status of knowledge. 

PMID- 23963323
TI  - Long-term outcome of insulin pump therapy in children with type 1 diabetes
      assessed in a large population-based case-control study.
AB  - AIMS/HYPOTHESIS: We determined the impact of insulin pump therapy on long-term
      glycaemic control, BMI, rate of severe hypoglycaemia and diabetic ketoacidosis
      (DKA) in children. METHODS: Patients on pump therapy at a single paediatric
      tertiary hospital were matched to patients treated by injections on the basis of
      age, duration of diabetes and HbA1c at the time of pump start. HbA1c,
      anthropometric data, episodes of severe hypoglycaemia and rates of
      hospitalisation for DKA were collected prospectively. RESULTS: A total of 345
      patients on pump therapy were matched to controls on injections. The mean age,
      duration of diabetes at pump start and length of follow-up were 11.4 (+/- 3.5),
      4.1 (+/- 3.0) and 3.5 (+/- 2.5) years, respectively. The mean HbA1c reduction in
      the pump cohort was 0.6% (6.6 mmol/mol). This improved HbA1c remained significant
      throughout the 7 years of follow-up. Pump therapy reduced severe hypoglycaemia
      from 14.7 to 7.2 events per 100 patient-years (p < 0.001). In contrast, severe
      hypoglycaemia increased in the non-pump cohort over the same period from 6.8 to
      10.2 events per 100 patient-years. The rate of hospitalisation for DKA was lower
      in the pump cohort (2.3 vs 4.7 per 100 patient-years, p = 0.003) over the 1,160
      patient-years of follow-up. CONCLUSIONS/INTERPRETATION: This is the longest and
      largest study of insulin pump use in children and demonstrates that pump therapy
      provides a sustained improvement in glycaemic control, and reductions of severe
      hypoglycaemia and hospitalisation for DKA compared with a matched cohort using
      injections.

PMID- 23963324
TI  - A role for adipocyte-derived lipopolysaccharide-binding protein in inflammation-
      and obesity-associated adipose tissue dysfunction.
AB  - AIMS/HYPOTHESIS: Circulating lipopolysaccharide-binding protein (LBP) is an acute
      phase reactant known to be increased in obesity. We hypothesised that LBP is
      produced by adipose tissue (AT) in association with obesity. METHODS: LBP mRNA
      and LBP protein levels were analysed in AT from three cross-sectional (n = 210, n
      = 144 and n = 28) and three longitudinal (n = 8, n = 25, n = 20) human cohorts;
      in AT from genetically manipulated mice; in isolated adipocytes; and in human and
      murine cell lines. The effects of a high-fat diet and exposure to
      lipopolysaccharide (LPS) and peroxisome proliferator-activated receptor
      (PPAR)gamma agonist were explored. Functional in vitro and ex vivo experiments
      were also performed. RESULTS: LBP synthesis and release was demonstrated to
      increase with adipocyte differentiation in human and mouse AT, isolated
      adipocytes and human and mouse cell lines (Simpson-Golabi-Behmel syndrome [SGBS],
      human multipotent adipose-derived stem [hMAD] and 3T3-L1 cells). AT LBP
      expression was robustly associated with inflammatory markers and increased with
      metabolic deterioration and insulin resistance in two independent cross-sectional
      human cohorts. AT LBP also increased longitudinally with weight gain and
      excessive fat accretion in both humans and mice, and decreased with weight loss
      (in two other independent cohorts), in humans with acquired lipodystrophy, and
      after ex vivo exposure to PPARgamma agonist. Inflammatory agents such as LPS and
      TNF-alpha led to increased AT LBP expression in vivo in mice and in vitro, while
      this effect was prevented in Cd14-knockout mice. Functionally, LBP knockdown
      using short hairpin (sh)RNA or anti-LBP antibody led to increases in markers of
      adipogenesis and decreased adipocyte inflammation in human adipocytes.
      CONCLUSIONS/INTERPRETATION: Collectively, these findings suggest that LBP might
      have an essential role in inflammation- and obesity-associated AT dysfunction.

PMID- 23963325
TI  - Imaging dynamics of CD11c+ cells and Foxp3+ cells in progressive autoimmune
      insulitis in the NOD mouse model of type 1 diabetes.
AB  - AIMS/HYPOTHESIS: The aim of this study was to visualise the dynamics and
      interactions of the cells involved in autoimmune-driven inflammation in type 1
      diabetes. METHODS: We adopted the anterior chamber of the eye (ACE)
      transplantation model to perform non-invasive imaging of leucocytes infiltrating
      the endocrine pancreas during initiation and progression of insulitis in the NOD
      mouse. Individual, ACE-transplanted islets of Langerhans were longitudinally and
      repetitively imaged by stereomicroscopy and two-photon microscopy to follow
      fluorescently labelled leucocyte subsets. RESULTS: We demonstrate that, in spite
      of the immune privileged status of the eye, the ACE-transplanted islets develop
      infiltration and beta cell destruction, recapitulating the autoimmune insulitis
      of the pancreas, and exemplify this by analysing reporter cell populations
      expressing green fluorescent protein under the Cd11c or Foxp3 promoters. We also
      provide evidence that differences in morphological appearance of subpopulations
      of infiltrating leucocytes can be correlated to their distinct dynamic behaviour.
      CONCLUSIONS/INTERPRETATION: Together, these findings demonstrate that the
      kinetics and dynamics of these key cellular components of autoimmune diabetes can
      be elucidated using this imaging platform for single cell resolution, non
      invasive and repetitive monitoring of the individual islets of Langerhans during
      the natural development of autoimmune diabetes.

PMID- 23963326
TI  - Phonological processing in Parkinson's disease: a neuropsychological assessment.
AB  - Patients with Parkinson's disease (PD) have cognitive deficits that cause
      functional impairments across several domains, including language. There is
      experimental evidence that basal ganglia and frontostriatal circuits are
      implicated in phonological processing, which leads to the hypothesis that a
      dysfunction of these circuits could be expressed behaviorally as phonological
      deficiencies in patients with PD. Using neuropsychological assessments, the
      present study aimed to explore the phonological processing abilities of patients
      in the initial stages of PD while controlling for other cognitive processes. The
      results showed lower scores in patients with PD on phonological tests with
      respect to a control group and these differences were independent of processes
      such as attention/working memory, long-term memory, thinking, and verbal language
      comprehension. However, there was an association between phonological skills and
      reading comprehension abilities. This finding implies a specific phonological
      deficit in terms of word reading. 

PMID- 23963327
TI  - Synthesis of 3-tetrazolylmethyl-azepino[4,5-b]indol-4-ones in two reaction steps:
      (Ugi-azide/N-acylation/SN2)/free radical cyclization and docking studies to a 5
      Ht(6) model.
AB  - A series of nine novel 3-tetrazolylmethyl-azepino[4,5-b]indol-4-ones were
      prepared in moderate to good overall yields in only two reaction steps. The first
      step consisted of a one-pot sequential process of an Ugi-azide multicomponent
      reaction, N-acylation and SN2 to give the xanthates. The second step was an
      intramolecular cyclization under free radical conditions. Also, their binding
      modes have been modelled using docking techniques. 

PMID- 23963328
TI  - Porous mesocarbon microbeads with graphitic shells: constructing a high-rate,
      high-capacity cathode for hybrid supercapacitor.
AB  - Li4Ti5O12/activated carbon hybrid supercapacitor can combine the advantages of
      both lithium-ion battery and supercapacitor, which may meet the requirements for
      developing high-performance hybrid electric vehicles. Here we proposed a novel
      "core-shell" porous graphitic carbon (PGC) to replace conventional activated
      carbon for achieving excellent cell performance. In this PGC structure made from
      mesocarbon microbead (MCMB), the inner core is composed of porous amorphous
      carbon, while the outer shell is graphitic carbon. The abundant porosity and the
      high surface area not only offer sufficient reaction sites to store electrical
      charge physically, but also can accelerate the liquid electrolyte to penetrate
      the electrode and the ions to reach the reacting sites. Meanwhile, the outer
      graphitic shells of the porous carbon microbeads contribute to a conductive
      network which will remarkably facilitate the electron transportation, and thus
      can be used to construct a high-rate, high-capacity cathode for hybrid
      supercapacitor, especially at high current densities.

PMID- 23963329
TI  - Elevated aerobic fitness sustained throughout the adult lifespan is associated
      with improved cerebral hemodynamics.
AB  - BACKGROUND AND PURPOSE: Age-related impairments in cerebral blood flow and
      cerebrovascular reactivity to carbon dioxide (CVRCO2) are established risk
      factors for stroke that respond favorably to aerobic training. The present study
      examined to what extent cerebral hemodynamics are improved when training is
      sustained throughout the adult lifespan. METHODS: Eighty-one healthy males were
      prospectively assigned to 1 of 4 groups based on their age (young, <=30 years
      versus old, >=60 years) and lifetime physical activity levels (trained, >=150
      minutes recreational aerobic activity/week versus sedentary, no activity). Middle
      cerebral artery blood velocity (MCAv, transcranial Doppler ultrasound), mean
      arterial pressure (MAP, finger photoplethysmography), and end-tidal partial
      pressure of carbon dioxide (PETCO2, capnography) were recorded during normocapnia
      and 3 mins of iso-oxic hypercapnea (5% CO2). Cerebrovascular
      resistance/conductance indices (CVRi/CVCi) were calculated as MAP/MCAv and
      MCAv/MAP, respectively, and CVRCO2 as the percentage increase in MCAv from
      baseline per millimeter of mercury (mm Hg) increase in PETCO2. Maximal oxygen
      consumption ( O2MAX, online respiratory gas analysis) was determined during
      cycling ergometry. RESULTS: By design, older participants were active for longer
      (49+/-5 versus 6+/-4 years, P<0.05). Physical activity attenuated the age-related
      declines in O2MAX, MCAv, CVCi, and CVRCO2 and increase in CVRi (P<0.05 versus
      sedentary). Linear relationships were observed between O2MAX and both MCAv and
      CVRCO2 (r=0.58-0.77, P<0.05). CONCLUSIONS: These findings highlight the
      importance of maintaining aerobic fitness throughout the lifespan given its
      capacity to improve cerebral hemodynamics in later-life.

PMID- 23963330
TI  - Prospective quality initiative to maximize dysphagia screening reduces hospital
      acquired pneumonia prevalence in patients with stroke.
AB  - BACKGROUND AND PURPOSE: Dysphagia can lead to pneumonia and subsequent death
      after acute stroke. However, no prospective study has demonstrated reduced
      pneumonia prevalence after implementation of a dysphagia screen. METHODS: We
      performed a single-center prospective interrupted time series trial of a quality
      initiative to improve dysphagia screening. Subjects included all patients with
      ischemic or hemorrhagic stroke admitted to our institution over 42 months with a
      31-month (n=1686) preintervention and an 11-month (n=648) postintervention
      period. The intervention consisted of a dysphagia protocol with a nurse
      administered bedside dysphagia screen and a reflexive rapid clinical swallow
      evaluation by a speech pathologist. RESULTS: The dysphagia initiative increased
      the percentage of patients with stroke screened from 39.3% to 74.2% (P<0.001).
      Furthermore, this initiative coincided with a drop in hospital-acquired pneumonia
      from 6.5% to 2.8% among patients with stroke (P<0.001). Patients admitted
      postinitiative had 57% lower odds of pneumonia, after controlling for multiple
      confounds (odds ratio=0.43; confidence interval, 0.255-0.711; P=0.0011). The best
      predictors of pneumonia were stroke type (P<0.0001), oral intake status
      (P<0.0001), dysphagia screening status (P=0.0037), and hospitalization before the
      beginning of the quality improvement initiative (P=0.0449). CONCLUSIONS: A
      quality improvement initiative using a nurse-administered bedside screen with
      rapid bedside swallow evaluation by a speech pathologist improves screening
      compliance and correlates with decreased prevalence of pneumonia among patients
      with stroke.

PMID- 23963332
TI  - New model for predicting surgical feeding tube placement in patients with an
      acute stroke event.
AB  - BACKGROUND AND PURPOSE: The need for surgical feeding tube placement after acute
      stroke can be uncertain and associated with further morbidity. METHODS:
      Retrospective data were recorded and compared across patients with acute ischemic
      stroke and intracerebral hemorrhage. We identified all feeding tubes placed as
      percutaneous endoscopic gastrostomy (PEG) tubes. A prediction score for PEG tube
      placement was developed separately for patients with acute ischemic stroke and
      intracerebral hemorrhage using logistic regression models of variables known by
      24 hours from admission. RESULTS: Of 407 patients included, 51 (12.5%) underwent
      PEG tube placement (25 acute ischemic stroke and 26 intracerebral hemorrhage).
      The odds of a patient with acute ischemic stroke with PEG score >=3 of getting a
      PEG are greater than those with PEG score <3 (odds ratio, 15.68; 95% confidence
      interval, 4.55-54.01). The odds of a patient with intracerebral hemorrhage with
      PEG score >=3 of getting a PEG are greater than those with PEG score <3 (odds
      ratio, 12.49; 95% confidence interval, 1.54-101.29). CONCLUSIONS: The PEG score,
      comprised by variables known within the first day of admission, may be a powerful
      predictor of PEG placement in patients with acute stroke.

PMID- 23963333
TI  - Mortality after ischemic stroke in patients with acute myocardial infarction:
      predictors and trends over time in Sweden.
AB  - BACKGROUND AND PURPOSE: Acute myocardial infarction (AMI) increases the risk of
      ischemic stroke, and mortality among these patients is high. Here, we aimed to
      estimate the 1-year mortality reliably after AMI complicated by ischemic stroke.
      We also aimed to identify trends over time for mortality during 1998-2008, as
      well as factors that predicted increased or decreased mortality. METHODS: Data
      for 173 233 unselected patients with AMI were collected from the Swedish Register
      of Information and Knowledge about Swedish Heart Intensive Care Admissions
      registry for 1998-2008. Specifically, we analyzed 1-year follow-up and mortality
      data for patients with AMI with and without ischemic stroke. Kaplan-Meyer
      analysis was used to analyze mortality trends over time, and Cox regression
      analysis was used to identify uni- and multivariate predictors of mortality.
      RESULTS: The 1-year mortality was 36.5% for AMI complicated by ischemic stroke
      and 18.3% for AMI without stroke. Mortality decreased over time in patients with
      and without ischemic stroke. The absolute decreases in mortality were 9.4% and
      7.5%, respectively. Reperfusion and secondary preventive therapies were
      associated with a decreased mortality rate. CONCLUSIONS: Mortality after AMI
      complicated by an ischemic stroke is very high but decreased from 1998 to 2008.
      The increased use of evidence-based therapies explains the improved prognosis.

PMID- 23963331
TI  - Granulocyte colony-stimulating factor in patients with acute ischemic stroke:
      results of the AX200 for Ischemic Stroke trial.
AB  - BACKGROUND AND PURPOSE: Granulocyte colony-stimulating factor (G-CSF; AX200;
      Filgrastim) is a stroke drug candidate with excellent preclinical evidence for
      efficacy. A previous phase IIa dose-escalation study suggested potential efficacy
      in humans. The present large phase IIb trial was powered to detect clinical
      efficacy in acute ischemic stroke patients. METHODS: G-CSF (135 ug/kg body weight
      intravenous over 72 hours) was tested against placebo in 328 patients in a
      multinational, multicenter, randomized, and placebo-controlled trial
      (NCT00927836; www.clinicaltrial.gov). Main inclusion criteria were <=9-hour time
      window after stroke onset, infarct localization in the middle cerebral artery
      territory, baseline National Institutes of Health Stroke Scale score range of 6
      to 22, and baseline diffusion-weighted imaging lesion size >=15 mL. Primary and
      secondary end points were the modified Rankin scale score and the National
      Institutes of Health Stroke Scale score at day 90, respectively. Data were
      analyzed using a prespecified model that adjusted for age, National Institutes of
      Health Stroke Scale score at baseline, and initial infarct volume (diffusion
      weighted imaging). RESULTS: G-CSF treatment failed to meet the primary and
      secondary end points of the trial. For additional end points such as mortality,
      Barthel index, or infarct size at day 30, G-CSF did not show efficacy either.
      There was, however, a trend for reduced infarct growth in the G-CSF group. G-CSF
      showed the expected peripheral pharmacokinetic and pharmacodynamic profiles, with
      a strong increase in leukocytes and monocytes. In parallel, the cytokine profile
      showed a significant decrease of interleukin-1. CONCLUSIONS: G-CSF, a novel and
      promising drug candidate with a comprehensive preclinical and clinical package,
      did not provide any significant benefit with respect to either clinical outcome
      or imaging biomarkers. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00927836.

PMID- 23963334
TI  - Intensity of anticoagulation and clinical outcomes in acute cardioembolic stroke:
      the Fukuoka Stroke Registry.
AB  - BACKGROUND AND PURPOSE: The relationship between the intensity of anticoagulation
      at the onset of acute cardioembolic stroke and clinical outcome after stroke is
      unclear. Here, we elucidated the relationship between prothrombin time
      international normalized ratio (PT-INR) values on admission and clinical outcomes
      in patients with acute cardioembolic stroke. METHODS: A total of 602 patients
      from the Fukuoka Stroke Registry in Japan who had been treated with warfarin but
      developed cardioembolic stroke were enrolled. The patients were classified into 3
      groups according to their PT-INR values on admission: PT-INR <1.50, 411 patients;
      PT-INR 1.50 to 1.99, 146 patients; and PT-INR >=2.00, 45 patients. The
      associations between PT-INR categories and severe neurological deficits (National
      Institutes of Health Stroke Scale >=10) on admission and poor functional outcome
      (modified Rankin scale 4-6) at discharge were investigated using a logistic
      regression analysis. RESULTS: Neurological deficits on admission were less
      severe, and functional outcome at discharge was more favorable as the PT-INR
      level on admission increased. The multivariate analysis revealed that severe
      neurological deficits were inversely associated with PT-INR on admission (PT-INR
      1.50-1.99: odds ratio, 0.66; 95% confidence interval, 0.43-1.00; PT-INR >=2.00:
      odds ratio, 0.41; 95% confidence interval, 0.20-0.83; compared with a reference
      group of PT-INR <1.50). Poor functional outcome was less likely in patients with
      PT-INR >=2.00 (odds ratio, 0.20; 95% confidence interval, 0.06-0.55) after
      adjustment for confounders. CONCLUSIONS: Prestroke PT-INR >=2.0 is associated
      with favorable clinical outcomes after acute cardioembolic stroke.

PMID- 23963335
TI  - Higher risk of recurrent ischemic events in patients with intracranial in-stent
      restenosis.
AB  - BACKGROUND AND PURPOSE: Reliable data concerning prognosis of patients with
      intracranial in-stent restenosis (ISR) is lacking. We prospectively studied long
      term outcomes of patients with and without a catheter angiography-verified ISR.
      METHODS: Between September 2001 and May 2009, 540 consecutive patients with
      symptomatic intracranial atherosclerosis received stenting treatment at our
      institute. Of them, 226 patients with 233 stented arteries had catheter
      angiography follow-up after stenting and were enrolled into this study. They were
      clinically followed up until the end of December 2011. Primary end point was
      ischemic stroke or transient ischemic attack in the territory of the stented
      artery after the catheter angiography follow-up. ISR was defined as a catheter
      angiography-verified stenosis of >=50% within or immediately adjacent (within
      range of 3 mm) to the implanted stent. RESULTS: During a mean follow-up of 38.9
      months, 27 (11.6%, 27/233) primary end point events were recorded. The risk of
      primary end point in ISR group was higher compared with non-ISR group (21.1%
      [12/57] versus 8.5% [15/176]; hazard ratio, 2.94; 95% confidence interval, 1.37
      6.30; P=0.005). Multivariable analysis showed that the ISR was an independent
      risk factor for the primary end point (hazard ratio, 2.79; 95% confidence
      interval, 1.20-6.49; P=0.017). The median occurrence time of primary end point
      was 9.9 (interquartile range, 5.0, 21.1) months in ISR group, earlier than that
      in non-ISR group (26.6 [13.1, 52.9] months; P=0.01). CONCLUSIONS: In-stent
      restenosis after stenting of intracranial atherosclerosis is significantly
      associated with an increased risk and an earlier occurrence of recurrent ischemic
      events in the territory of the stented intracranial artery.

PMID- 23963336
TI  - Techniques for processing eyes implanted with a retinal prosthesis for localized
      histopathological analysis.
AB  - With the recent development of retinal prostheses, it is important to develop
      reliable techniques for assessing the safety of these devices in preclinical
      studies. However, the standard fixation, preparation, and automated histology
      procedures are not ideal. Here we describe new procedures for evaluating the
      health of the retina directly adjacent to an implant. Retinal prostheses feature
      electrode arrays in contact with eye tissue. Previous methods have not been able
      to spatially localize the ocular tissue adjacent to individual electrodes within
      the array. In addition, standard histological processing often results in gross
      artifactual detachment of the retinal layers when assessing implanted eyes.
      Consequently, it has been difficult to assess localized damage, if present,
      caused by implantation and stimulation of an implanted electrode array.
      Therefore, we developed a method for identifying and localizing the ocular tissue
      adjacent to implanted electrodes using a (color-coded) dye marking scheme, and we
      modified an eye fixation technique to minimize artifactual retinal detachment.
      This method also rendered the sclera translucent, enabling localization of
      individual electrodes and specific parts of an implant. Finally, we used a
      matched control to increase the power of the histopathological assessments. In
      summary, this method enables reliable and efficient discrimination and assessment
      of the retinal cytoarchitecture in an implanted eye.

PMID- 23963337
TI  - Bis-cyclometallated gold(III) complexes as efficient catalysts for synthesis of
      propargylamines and alkylated indoles.
AB  - Stable bis-cyclometallated gold(III) complexes were developed as efficient
      catalysts for organic transformation reactions by using two strategies: (1)
      construction of distorted square planar gold(III) complexes and (2) dual
      catalysis by gold(III) complexes and silver salts.

PMID- 23963338
TI  - Different cell responses induced by exposure to maghemite nanoparticles.
AB  - Recent advances in nanotechnology have permitted the development of a wide
      repertoire of inorganic magnetic nanoparticles (NPs) with extensive promise for
      biomedical applications. Despite this remarkable potential, many questions still
      arise concerning the biocompatible nature of NPs when in contact with biological
      systems. Herein, we have investigated how controlled changes in the
      physicochemical properties of iron oxide NPs at their surface (i.e., surface
      charge and hydrodynamic size) affect, first, their interaction with cell media
      components and, subsequently, cell responses to NP exposure. For that purpose, we
      have prepared iron oxide NPs with three different coatings (i.e.,
      dimercaptosuccinic acid - DMSA, (3-aminopropyl)triethoxysilane - APS and dextran)
      and explored the response of two different cell types, murine L929 fibroblasts
      and human Saos-2 osteoblasts, to their exposure. Interestingly, different cell
      responses were found depending on the NP concentration, surface charge and cell
      type. In this sense, neutral NPs, as those coated with dextran, induced
      negligible cell damage, as their cellular internalization was significantly
      reduced. In contrast, surface-charged NPs (i.e., those coated with DMSA and APS)
      caused significant cellular changes in viability, morphology and cell cycle under
      certain culture conditions, as a result of a more active cellular
      internalization. These results also revealed a particular cellular ability to
      detect and remember the original physicochemical properties of the NPs, despite
      the formation of a protein corona when incubated in culture media. Overall,
      conclusions from these studies are of crucial interest for future biomedical
      applications of iron oxide NPs. 

PMID- 23963339
TI  - Changes in thresholds for intracortical excitability in chronic stroke: more than
      just altered intracortical inhibition.
AB  - PURPOSE: The purpose of the present study was to assess changes in thresholds for
      the onset of short intracortical inhibition (SICI) and intracortical facilitation
      (ICF) in individuals with chronic stroke compared to age-matched healthy adults
      and evaluate the relationship between these thresholds and motor function in the
      chronic stroke group. METHODS: Paired-pulse transcranial magnetic stimulation was
      used to derive thresholds for the onset of SICI and ICF in 12 neurologically
      healthy and 12 individuals with chronic stroke. Motor evoked potentials were
      elicited by a test stimulus of fixed intensity preceded by a conditioning
      stimulus ranging from 0%-125% of active motor threshold to generate recruitment
      curves. Regression functions were fit to these recruitment curves to identify
      thresholds for the onset of SICI and ICF. Mixed measures analysis of variance was
      used to compare thresholds for each hemisphere within and between groups.
      RESULTS: Results showed a significant three-way interaction between Group
      (stroke, healthy), Hemisphere (ipsilesional, contralesional) and Stimulus
      interval (2 ms, 12 ms). Significant differences in the thresholds for the onset
      of both SICI and ICF were present in individuals with chronic stroke, with no
      between hemisphere differences for the control group. When compared to age
      matched controls, comparisons revealed significant reductions in ipsilesional,
      but not contralesional thresholds for the onset of ICF, and significant
      reductions in contralesional, but not ipsilesional, thresholds for the onset of
      SICI in individuals with chronic stroke. In addition, as thresholds for ICF and
      SICI in stroke patients approached the level of healthy adults, higher function
      on the Wolf Motor Function Test was observed. CONCLUSIONS: Reduced thresholds for
      the onset of SICI and ICF observed in the present study indicate that both
      inhibitory and facilitatory systems mediate changes in cortical excitability in
      chronic stroke patients. The association between higher onset thresholds and
      motor function in the stroke group also suggests that these thresholds have
      potential utility for tracking functional motor improvements in patients with
      chronic stroke. This study provides new insights to further characterize changes
      in intracortical neurotransmission that play an important role in modulating
      neuroplasticity and the potential relationship between inhibitory and
      facilitatory networks and motor function post-stroke.

PMID- 23963340
TI  - The effect of EMG triggered electrical stimulation plus task practice on arm
      function in chronic stroke patients with moderate-severe arm deficits.
AB  - PURPOSE: We examined the feasibility and outcome of electromyographically
      triggered electrical muscle stimulation (EMG-ES) plus unilateral or bilateral
      task specific practice on arm function in chronic stroke survivors with moderate
      severe hemiplegia. Transcranial magnetic stimulation was used to examine inter
      hemispheric inhibition (IHI) acting on the stroke-affected hemisphere in a subset
      of eight participants. METHODS: Twenty-one stroke survivors (14 males; mean time
      post stroke 57.9 months) participated in this pilot investigation. Participants
      underwent a six-week program of daily EMG-ES training with random assignment to
      concurrent task practice using the stroke-affected hand only or both hands. The
      upper-extremity subscale of the Fugl-Meyer (FMUE) and the Arm Motor Ability Test
      (AMAT) were completed at baseline, 0-, 1-, and 3-months post-intervention.
      RESULTS: Following the intervention, FMUE (F(3, 57) = 3.89, p = .01, etap2 = .17)
      and AMAT (F(3, 57) = 12.6, p = .01, etap2 = .39) scores improved, and remained
      better than baseline at three months re-assessment. The difference between groups
      was not significant. A non-significant decrease in IHI was observed post
      intervention. CONCLUSIONS: An intensive program of EMG-ES assisted functional
      training is feasible, well tolerated, and leads to improvements in moderate
      severe deficits of arm function post stroke. Larger placebo controlled studies
      are needed to explore any advantage of bilateral over unilateral EMG-ES assisted
      training.

PMID- 23963341
TI  - Understanding upper limb recovery after stroke.
AB  - This review addresses what is currently known about the time course of skill
      reacquisition after stroke. There is growing evidence that the natural
      logarithmic pattern of functional recovery can be modified by intensive task
      oriented practice preferably initiated within 6 months after stroke. However, the
      impact of practice on the learning-dependent and intrinsic spontaneous mechanisms
      of neurological recovery is poorly understood. At least four probably
      interrelated mechanisms have been identified that drive motor and recovery after
      stroke: (1) salvation of penumbral tissue in the first days to weeks after
      stroke; (2) alleviation of diaschisis; (3) homeostatic and learning-dependent
      (Hebbian) neuroplasticity; (4) behavioral compensation strategies. These
      mechanisms underlying recovery are highly interactive, and operate in different,
      sometimes limited, time-windows after stroke onset. In line with these mechanisms
      of improvement after stroke, we present a hypothetical phenomenological model for
      understanding skill reacquisition after stroke. Translational research is
      important at this point to improve our knowledge about the neural correlates of
      what and how patients learn when they show functional improvement after stroke.
      This knowledge should serve as a basis to optimize the timing, focus and
      intensity of evidence-based rehabilitation interventions and to design innovative
      strategies to enhance motor recovery after stroke. 

PMID- 23963342
TI  - Remnant Pachira quinata pasture trees have greater opportunities to self and
      suffer reduced reproductive success due to inbreeding depression.
AB  - Habitat fragmentation is extensive throughout the world, converting natural
      ecosystems into fragments of varying size, density and connectivity. The
      potential value of remnant trees in agricultural landscapes as seed sources and
      in connecting fragments has formed a fertile area of debate. This study
      contrasted the mating patterns of bat-pollinated Pachira quinata trees in a
      continuous forest to those in pasture through microsatellite-based paternity
      analysis of progeny. The breeding system was determined by analysis of pollen
      tube growth and seed production from controlled pollinations. Fitness of selfed
      and outcrossed seed was compared by germination and seedling growth. There was
      more inbreeding within pasture trees (outcrossing=0.828+/-0.015) compared with
      forest trees (0.926+/-0.005). Pasture trees had fewer sires contributing to
      mating events, but pollen dispersal distances were greater than those in the
      forest. Paternity analysis showed variation in outcrossing rates among pasture
      trees with high proportions of external and self pollen sources detected. A leaky
      self-incompatibility system was found, with self pollen having reduced
      germination on stigmas and slower growth rate through the style. Controlled
      pollinations also showed a varied ability to self among trees, which was
      reflected in the selfing rates among pasture trees shown by the paternity
      analysis (0-80% selfing). Self pollination resulted in lower seed set,
      germination and seedling growth compared with outcrossing. While remnant trees in
      agricultural landscapes are involved in broader mating patterns, they show
      increased but varied levels of inbreeding, which result in reduced fitness. 

PMID- 23963344
TI  - Reconstruction of skin avulsion injuries of the upper extremity with integra((r))
      dermal regeneration template and skin grafts in a single-stage procedure.
AB  - INTRODUCTION: Management of skin avulsion injuries of the upper extremity may
      require coverage with large flaps or skin autografts. Cutaneous grafting is
      frequently combined with artificial skin to optimize the final functional and
      cosmetic result. The conventional use of bilaminated dermal substitutes consists
      of a two-stage procedure and requires long immobilization of the operated area.
      The purpose of this retrospective study is to evaluate the impact of a dermal
      regeneration template immediately covered by skin grafts in a one-step procedure
      for reconstructing skin avulsion injuries of the hand and forearm. MATERIALS AND
      METHODS: We performed this technique in eight patients who presented with
      extended skin defects of the hand and forearm following skin avulsion injuries.
      Dimensions of the defects ranged from 160 to 1,250 cm(2). After debridement,
      Integra((r)) Single Layer was applied and covered with unmeshed thin skin
      autografts; compressive dressings were used for 1 week and mobilization started
      by the second postoperative week. Histological examination of the grafted areas
      was performed 2 weeks after surgery. Functional and cosmetic outcome was assessed
      12 months postoperatively. RESULTS: The overall take rate of the dermal
      substitute and skin graft was 95-98 %. Histological results showed complete
      incorporation and vascular proliferation of the template, which allowed the neo
      vascularization of the overlying autograft. The mean grip strength of the
      operated hands was at the 83 % of the normal contralateral hands. Pliability and
      overall appearance of the reconstructed areas was satisfactory (mean Vancouver
      Scar Scale Score 1.875). CONCLUSIONS: The use of Integra((r)) Single Layer dermal
      substitute and immediate skin overgrafting consists an alternative reconstructive
      option for managing extended skin avulsion injuries of the upper extremity; it
      reduces postoperative immobilization, minimizes donor site morbidity and provides
      good functional and esthetic results in a single surgical procedure.

PMID- 23963343
TI  - Key questions in the genetics and genomics of eco-evolutionary dynamics.
AB  - Increasing acceptance that evolution can be 'rapid' (or 'contemporary') has
      generated growing interest in the consequences for ecology. The genetics and
      genomics of these 'eco-evolutionary dynamics' will be--to a large extent--the
      genetics and genomics of organismal phenotypes. In the hope of stimulating
      research in this area, I review empirical data from natural populations and draw
      the following conclusions. (1) Considerable additive genetic variance is present
      for most traits in most populations. (2) Trait correlations do not consistently
      oppose selection. (3) Adaptive differences between populations often involve
      dominance and epistasis. (4) Most adaptation is the result of genes of small-to
      modest effect, although (5) some genes certainly have larger effects than the
      others. (6) Adaptation by independent lineages to similar environments is mostly
      driven by different alleles/genes. (7) Adaptation to new environments is mostly
      driven by standing genetic variation, although new mutations can be important in
      some instances. (8) Adaptation is driven by both structural and regulatory
      genetic variation, with recent studies emphasizing the latter. (9) The ecological
      effects of organisms, considered as extended phenotypes, are often heritable.
      Overall, the study of eco-evolutionary dynamics will benefit from perspectives
      and approaches that emphasize standing genetic variation in many genes of small
      to-modest effect acting across multiple traits and that analyze overall
      adaptation or 'fitness'. In addition, increasing attention should be paid to
      dominance, epistasis and regulatory variation.

PMID- 23963346
TI  - Shifting from laparotomy to thoracoscopic repair of congenital diaphragmatic
      hernia in neonates: early experience.
AB  - BACKGROUND: Thoracoscopic repair of congenital diaphragmatic hernia (CDH) is now
      widely performed by pediatric surgeons. We compare our experience with this
      operation versus the results for a group of CDH patients treated by laparotomy at
      the same center over the same period. METHODS: From January 2008 to December
      2011, we reviewed the medical records of 50 neonates who underwent surgery for
      posterolateral CDH (34 by laparotomy, 16 by thoracoscopy). Two thoracoscopic
      operations (12.5 %) were converted to thoracotomy. Eight patients treated with
      extracorporeal membrane oxygenation (ECMO) underwent laparotomy. RESULTS: There
      were no significant differences in demographic characteristics between the two
      groups. Both nitric oxide (p = 0.13) and high-frequency oscillatory ventilation
      (p = 0.06) tended to be required more frequently in the laparotomy group than in
      the thoracoscopy group. A patch was applied to nine patients (five laparotomy,
      four thoracoscopy, p = 0.42). Mean operation time was longer for the thoracoscopy
      group, but not significantly so (p = 0.06). Times to feeding and lengths of
      hospital stays were similar, as were days of postoperative ventilator use and of
      total ventilator use. CDH recurred in two patients, both in the thoracoscopy
      group (p = 0.08), and intestinal obstruction occurred in five patients in the
      laparotomy group. Of eight patients who received ECMO treatment, only three
      survived. CONCLUSIONS: Except in patients receiving ECMO treatment, thoracoscopic
      repair is useful and feasible regardless of defect size or need for patching.
      Operation time is longer, but cosmetic appearance is better and intestinal
      obstruction uppers to be less frequent. However, intensive training is needed to
      prevent the recurrence.

PMID- 23963347
TI  - Repeat hepatectomy for recurrent liver metastasis from gastric carcinoma.
AB  - BACKGROUND: The efficacy of repeat hepatectomy for recurrent hepatocellular
      carcinoma and colorectal liver metastases is widely accepted. However, the
      benefits of such treatment for intrahepatic recurrence of gastric cancer liver
      metastasis remain unknown. This study sought to clarify the survival benefit for
      patients undergoing repeat hepatectomy for gastric cancer liver metastasis.
      METHODS: A total of 73 patients underwent hepatectomy for gastric cancer liver
      metastasis from January 1993 to January 2011. Macroscopically curative surgery
      was performed in 64 patients. Among them, repeat hepatectomy was performed in 14
      of the 37 patients with intrahepatic recurrence. Among these 14 patients,
      clinicopathologic factors were evaluated by univariate and multivariate analysis
      to identify the factors affecting survival. RESULTS: The overall 1-, 3-, and 5
      year survival rates after a second hepatectomy were 71, 47, and 47 %,
      respectively. The median survival was 31 months. Operative morbidity and
      mortality rates of repeat hepatectomy were 29 and 0 %, respectively. Multivariate
      analysis identified the duration of the disease-free interval as the only
      independent significant factor predicting better survival. CONCLUSIONS: In
      selected patients, repeat hepatectomy for recurrent gastric cancer liver
      metastasis may offer the same chance of cure as the primary hepatectomy. Disease
      free intervals exceeding 12 months predict good patient survival after repeat
      hepatectomy.

PMID- 23963348
TI  - Is mode of presentation of B3 breast core biopsies (screen-detected or
      symptomatic) a distinguishing factor in the final histopathologic result or risk
      of diagnosis of malignancy?
AB  - BACKGROUND: The relation between histopathologic subclassification and mode of
      patient presentation (with a screen-detected vs. symptomatic lesion) with an
      abnormality in the breast core biopsy classified as having uncertain malignant
      potential (B3) has not been previously examined. We compared the histopathologic
      subclassification of these lesions and the frequency of malignancy in screen
      detected and symptomatic patient groups. METHODS: All B3 core biopsies from one
      breast unit at the Royal Berkshire Hospital over a 5-year period (2006-2010) were
      analyzed (n = 131). After dividing the B3 biopsies into screen-detected and
      symptomatic groups, the National Health Service Breast Screening Programme
      histopathologic subclassification was used to further divide the groups into six
      subtypes. After surgery, a final diagnosis of invasive or in situ carcinoma was
      also noted. RESULTS: B3 classification comprised 3.8 % (131/3,440) of all core
      biopsies during that time period. There were 78 specimens from symptomatic (59 %)
      and 53 from screen-detected (41 %) patients. There was no statistically
      significant difference between papillary and fibroepithelial diagnoses between
      the two groups (47 vs. 42 %, p = 0.59, NS). There was no difference between the
      groups for atypia, lobular neoplasia, or sclerosing lesions (49 vs. 51 %, p =
      0.8, NS). Cancer was found in 20 % of the symptomatic patients and in 17 % of the
      screen-detected group (p = 0.65, NS). CONCLUSIONS: Mode of patient presentation
      (with a screen-detected or symptomatic lesion) was not a distinguishing factor
      for breast histopathologic subclassification or for the final cancer diagnosis in
      patients whose breast core biopsy was classified as B3.

PMID- 23963350
TI  - Evidence of Gumbel distributions  of conductance fluctuations in 
      bacteriorhodopsin thin films.
AB  - By considering a set of experiments carried out on bacteriorhodopsin in vitro by
      Casuso et al (2007 Phys. Rev. E 76 041919), we extract the conductance as
      function of the applied voltage. The microscopic interpretation of experiments
      shows that charge transfer is ruled by a direct tunneling (DT) mechanism at low
      bias and by a Fowler-Nordheim (FN) tunneling mechanism at high bias. A nucleation
      region at the cross-over between the DT and FN regimes can be identified. A
      theoretical analysis of conductance fluctuations is performed by calculating the
      corresponding variance and the probability density functions (PDFs): these
      constitute a powerful indicator in order to understand the internal dynamics of
      the system. Conductance fluctuations are non-Gaussian and follow well the
      standard generalized Gumbel distributions G(a). In particular, at low bias, the
      PDFs are bimodal and can be resolved in at least a couple of G(a) functions with
      different values of the shape parameter a. The nucleation region is characterized
      by a single Gumbel distribution, G(1). At increasing bias, the G(1) distribution
      turns in a bimodal distribution. We discuss possible correlations between the
      voltage dependence of the G(a) and the microscopic mechanisms that determine the
      electrical response of the system.

PMID- 23963349
TI  - Single dual-trained surgeon for breast care leads to higher reconstruction rates
      after mastectomy.
AB  - BACKGROUND: Breast reconstruction improves the quality of life for mastectomy
      patients but is underutilized in the United States. This study investigated
      reconstruction rates for a dual-trained oncologic plastic surgeon to explore how
      provider-based factors influence reconstruction. METHODS: We evaluated
      consecutive mastectomy patients treated at the University of California, San
      Diego Medical Center between 2009 and 2012. We identified mastectomy patients
      based on Current Procedural Terminology codes and evaluated them for patient- and
      disease-specific variables. We evaluated reconstruction rates for the traditional
      team model of collaborating plastic and oncologic surgeons versus a single
      surgeon, dual trained in surgical breast oncology and plastic surgery. A
      multivariate regression analysis was then used to identify the significant
      predictors of reconstruction. RESULTS: Mastectomy was performed in 344 patients.
      The surgeon group was a significant predictor of postmastectomy reconstruction (p
      < 0.05). The traditional team of oncologic and plastic surgeons reconstructed 93
      (63.3 %) of 147 mastectomy patients, whereas the single dual-trained surgeon
      reconstructed 140 (71.1 %) of 197 mastectomy patients. Race and insurance status
      did not influence the receipt of reconstruction in our single-surgeon model,
      however, patients of older age [odds ratio (OR) 0.93, confidence interval (CI)
      0.89-0.98, p < 0.01], higher body mass index (OR 0.89, CI 0.82-0.97, p < 0.01),
      or more advanced disease (p < 0.01) were less likely to undergo reconstruction.
      CONCLUSIONS: A single dual-trained surgeon for breast care influences
      reconstruction rates. A dual-trained surgeon increases the likelihood of
      reconstruction and obtains rates higher than previously reported. This may
      reflect the comprehensive care provided by a multidisciplinary-trained
      professional. A single surgeon providing care in oncology and reconstruction
      represents a comprehensive approach to breast care and demonstrates a
      relationship between provider practice and breast reconstruction.

PMID- 23963351
TI  - Patterns of disease progression on 18F-fluorodeoxyglucose positron emission
      tomography-computed tomography in patients with malignant pleural mesothelioma
      undergoing multimodality therapy with pleurectomy/decortication.
AB  - INTRODUCTION: The aim of this study was to evaluate the patterns of disease
      progression in patients treated with pleurectomy/decortication (P/D),
      hyperthermic pleural lavage with povidone-iodine, prophylactic radiotherapy and
      adjuvant chemotherapy, using F-fluorodeoxyglucose (18F-FDG) PET/computed
      tomography (PET/CT). MATERIALS AND METHODS: This was a retrospective study of 65
      patients treated with a multimodality therapy including P/D between October 2004
      and March 2012. Thirty-two patients underwent 18F-FDG PET/CT within 6 weeks of
      completion of adjuvant chemotherapy and 6-monthly thereafter at our institution.
      The first site of relapse on 18F-FDG PET/CT was recorded, and all scans were
      reviewed by an independent observer. RESULTS: Thirty-two patients (27 male,
      median age 61 years, range 45-73) underwent their 18F-FDG PET/CT scans at our
      institution. Eighteen of the 32 patients were alive at last follow-up (median
      follow-up 42 months, range 16-76). Nine patients were alive with disease
      recurrence. Fourteen patients died of disease progression (median survival 24.7
      months, range 15-38). The median maximum standardized uptake value (SUVmax) in
      relapsing mesothelioma was 10.9 (range 4.9-27.3). There was a statistically
      significant correlation between the SUVmax and tumour lesion glycolysis of
      recurrent mesothelioma and overall survival (P=0.05). The site of disease
      recurrence was the pleura in the majority of the alive patients and was
      extrapleural in the dead patients. There was a statistically significant
      correlation between disease-free survival and complete macroscopic resection
      (P=0.02). CONCLUSION: After P/D with hyperthermic pleural lavage with povidone
      iodine, prophylactic radiotherapy and adjuvant chemotherapy, the most frequent
      site of recurrence is the pleural cavity. Peritoneal seeding is rare. The tumour
      SUVmax and tumour lesion glycolysis correlate significantly with overall
      survival.

PMID- 23963352
TI  - Comparison of fragmented QRS and myocardial perfusion-gated SPECT findings.
AB  - AIM: Fragmented QRS (fQRS) complex is an ECG parameter that has recently been
      introduced and investigated. It is assumed that fQRS occurs because of
      disruptions in ventricular conduction due to ventricular infarction and ischemia.
      Therefore, in this article, we aimed to investigate the relationship between the
      detection of infarction and ischemia on myocardial perfusion-gated single-photon
      emission computed tomography images and appearance of fQRS on ECG. MATERIALS AND
      METHODS: We retrospectively reviewed the records of patients with a diagnosis of
      coronary artery disease who were referred to our institution for myocardial
      perfusion scintigraphy. In total, 261 patients (122 women and 139 men, with a
      mean age of 61+/-10.33 years) with and without fQRS (136 and 125, respectively)
      were included in the present study. The myocardial perfusion scintigraphy results
      were evaluated for the presence or absence of myocardial ischemia and infarction
      by visual and quantitative (summed stress score, summed rest, summed difference
      score, summed motion score, and summed thickening score) assessments. Statistical
      analysis was performed to determine the relationship between the presence of fQRS
      and myocardial ischemia and/or infarction. Student's t-test and the Mann-Whitney
      U-test were used for comparing the results. Pearson's chi2-test and Fisher's
      exact tests were also used to compare the distribution of variables between the
      two groups. RESULTS: The prevalence of ischemia and infarction were found to be,
      respectively, 4.38-fold and 5.95-fold higher in patients with fQRS compared with
      the control group. Moreover, the prevalence of both ischemia and infarction was
      found to be 10.54-fold higher in patients with fQRS compared with the control
      group. CONCLUSION: There is a highly statistically significant possibility of
      detecting ischemia and infarction in perfusion myocardial scintigrams of patients
      whose ECGs have fQRS.

PMID- 23963353
TI  - Accelerated rate of molecular evolution for vittarioid ferns is strong and not
      driven by selection.
AB  - Molecular evolutionary rate heterogeneity-the violation of a molecular clock-is a
      prominent feature of many phylogenetic data sets. It has particular importance to
      systematists not only because of its biological implications, but also for its
      practical effects on our ability to infer and date evolutionary events. Here we
      show, using both maximum likelihood and Bayesian approaches, that a remarkably
      strong increase in substitution rate in the vittarioid ferns is consistent across
      the nuclear and plastid genomes. Contrary to some expectations, this rate
      increase is not due to selective forces acting at the protein level on our focal
      loci. The vittarioids bear no signature of the change in the relative strengths
      of selection and drift that one would expect if the rate increase was caused by
      altered post-mutation fixation rates. Instead, the substitution rate increase
      appears to stem from an elevated supply of mutations, perhaps limited to the
      vittarioid ancestral branch. This generalized rate increase is accompanied by
      extensive fine-scale heterogeneity in rates across loci, genomes, and taxa. Our
      analyses demonstrate the effectiveness and flexibility of trait-free
      investigations of rate heterogeneity within a model-selection framework,
      emphasize the importance of explicit tests for signatures of selection prior to
      invoking selection-related or demography-based explanations for patterns of rate
      variation, and illustrate some unexpected nuances in the behavior of relaxed
      clock methods for modeling rate heterogeneity, with implications for our ability
      to confidently date divergence events. In addition, our data provide strong
      support for the monophyly of Adiantum, and for the position of Calciphilopteris
      in the cheilanthoid ferns, two relationships for which convincing support was
      previously lacking.

PMID- 23963354
TI  - Differential lung NK cell responses in avian influenza virus infected chickens
      correlate with pathogenicity.
AB  - Infection of chickens with low pathogenicity avian influenza (LPAI) virus results
      in mild clinical signs while infection with highly pathogenic avian influenza
      (HPAI) viruses causes death of the birds within 36-48 hours. Since natural killer
      (NK) cells have been shown to play an important role in influenza-specific
      immunity, we hypothesise that NK cells are involved in this difference in
      pathogenicity. To investigate this, the role of chicken NK-cells in LPAI virus
      infection was studied. Next activation of lung NK cells upon HPAI virus infection
      was analysed. Infection with a H9N2 LPAI virus resulted in the presence of viral
      RNA in the lungs which coincided with enhanced activation of lung NK cells. The
      presence of H5N1 viruses, measured by detection of viral RNA, did not induce
      activation of lung NK cells. This suggests that decreased NK-cell activation may
      be one of the mechanisms associated with the enhanced pathogenicity of H5N1
      viruses. 

PMID- 23963355
TI  - Randomized, multicenter trial to assess the efficacy, safety and tolerability of
      a single dose of a novel AMPA receptor antagonist BGG492 for the treatment of
      acute migraine attacks.
AB  - BACKGROUND: Glutamate is implicated in migraine pathophysiology; amino-3-hydroxy
      5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists represent a
      potential therapeutic approach because of their anti-excitatory actions. METHODS:
      This randomized, double-blind, proof-of-concept study assessed the efficacy of
      the AMPA receptor antagonist, BGG492 (250 mg), vs placebo and sumatriptan (100
      mg), in 75 subjects with acute migraine attacks. Efficacy was measured using the
      Patient Migraine Diary. Pharmacokinetic and safety data were collected. RESULTS:
      Improvement from severe/moderate to mild/no headache pain (primary response) was
      reported in 58%, 58%, and 54% of BGG492-treated subjects at 2, 3, and 4 hours
      post-dose ( P = 0.2, 0.5, and 0.5 vs placebo), respectively, compared with 68%,
      84%, and 92% sumatriptan-treated subjects, and 40%, 48%, and 44% in the placebo
      group. Percentages of subjects with >= 2-point improvement in pain score from
      baseline at 2 hours were 29%, 40%, and 16% for BGG492, sumatriptan, and placebo,
      respectively. Pain-free response at 2 hours was reported for 25%, 24%, and 16% of
      BGG492, sumatriptan, and placebo subjects, respectively. Adverse events were
      reported by 80%, 56%, and 60% of BGG492, sumatriptan, and placebo subjects,
      respectively. CONCLUSIONS: Proof-of-concept criterion was not met (>= 25% BGG492
      subjects with a primary response vs placebo at two timepoints). BGG492 was
      comparable to sumatriptan in terms of pain-free response.

PMID- 23963356
TI  - Duration of migraine aura.

PMID- 23963357
TI  - Pitfalls for readers of "special issue on pearls and pitfalls in headache
      research".

PMID- 23963358
TI  - Microwave photonics systems based on whispering-gallery-mode resonators.
AB  - Microwave photonics systems rely fundamentally on the interaction between
      microwave and optical signals. These systems are extremely promising for various
      areas of technology and applied science, such as aerospace and communication
      engineering, sensing, metrology, nonlinear photonics, and quantum optics. In this
      article, we present the principal techniques used in our lab to build microwave
      photonics systems based on ultra-high Q whispering gallery mode resonators. First
      detailed in this article is the protocol for resonator polishing, which is based
      on a grind-and-polish technique close to the ones used to polish optical
      components such as lenses or telescope mirrors. Then, a white light
      interferometric profilometer measures surface roughness, which is a key parameter
      to characterize the quality of the polishing. In order to launch light in the
      resonator, a tapered silica fiber with diameter in the micrometer range is used.
      To reach such small diameters, we adopt the "flame-brushing" technique, using
      simultaneously computer-controlled motors to pull the fiber apart, and a
      blowtorch to heat the fiber area to be tapered. The resonator and the tapered
      fiber are later approached to one another to visualize the resonance signal of
      the whispering gallery modes using a wavelength-scanning laser. By increasing the
      optical power in the resonator, nonlinear phenomena are triggered until the
      formation of a Kerr optical frequency comb is observed with a spectrum made of
      equidistant spectral lines. These Kerr comb spectra have exceptional
      characteristics that are suitable for several applications in science and
      technology. We consider the application related to ultra-stable microwave
      frequency synthesis and demonstrate the generation of a Kerr comb with GHz
      intermodal frequency. 

PMID- 23963359
TI  - Prediction of different types of liver diseases using rule based classification
      model.
AB  - BACKGROUND: Diagnosing different types of liver diseases clinically is a quite
      hectic process because patients have to undergo large numbers of independent
      laboratory tests. On the basis of results and analysis of laboratory test,
      different liver diseases are classified. Hence to simplify this complex process,
      we have developed a Rule Base Classification Model (RBCM) to predict different
      types of liver diseases. The proposed model is the combination of rules and
      different data mining techniques. OBJECTIVE: The objective of this paper is to
      propose a rule based classification model with machine learning techniques for
      the prediction of different types of Liver diseases. METHOD: A dataset was
      developed with twelve attributes that include the records of 583 patients in
      which 441 patients were male and rests were female. Support Vector Machine (SVM),
      Rule Induction (RI), Decision Tree (DT), Naive Bayes (NB) and Artificial Neural
      Network (ANN) data mining techniques with K-cross fold technique are used with
      the proposed model for the prediction of liver diseases. The performance of these
      data mining techniques are evaluated with accuracy, sensitivity, specificity and
      kappa parameters as well as statistical techniques (ANOVA and Chi square test)
      are used to analyze the liver disease dataset and independence of attributes.
      RESULT: Out of 583 patients, 416 patients are liver diseases affected and rests
      of 167 patients are healthy. The proposed model with decision tree (DT) technique
      provides the better result among all techniques (RI, SVM, ANN and NB) with all
      parameters (Accuracy 98.46%, Sensitivity 95.7%, Specificity 95.28% and Kappa
      0.983) while the SVM exhibits poor performance (Accuracy 82.33%, Sensitivity
      68.03%, Specificity 91.28% and Kappa 0.801). It is also found that the best
      performance of the model without rules (RI, Accuracy 82.68%, Sensitivity 86.34%,
      Specificity 90.51% and Kappa 0.619) is almost similar to the worst performance of
      the rule based classification model (SVM, Accuracy 82.33%, Sensitivity 68.03%,
      Specificity 91.28% and Kappa 0.801 and the accuracy of chi square test is 76.67%.
      CONCLUSION: This study demonstrates that there is a significant difference
      between the proposed rules based classification model and the model without rules
      for the liver diseases prediction and the rule based classification model with
      decision tree (DT) technique provides most accurate result. This model can be
      used as a valuable tool for medical decision making.

PMID- 23963360
TI  - Combining erlotinib and cetuximab is associated with activity in patients with
      non-small cell lung cancer (including squamous cell carcinomas) and wild-type
      EGFR or resistant mutations.
AB  - Preclinical data suggest that combined EGF receptor (EGFR) targeting with an EGFR
      tyrosine kinase inhibitor and an anti-EGFR monoclonal antibody may be superior
      over single-agent targeting. Therefore, as part of a phase I study, we analyzed
      the outcome of 20 patients with non-small cell lung cancer treated with the
      combination of erlotinib and cetuximab. EGFR mutation status was ascertained in a
      Clinical Laboratory Improvement Amendment-approved laboratory. There were 10 men;
      median number of prior therapies was five. Overall, two of 20 patients (10%)
      achieved partial response (PR), one of whom had a TKI-resistant EGFR insertion in
      exon 20, time to treatment failure (TTF) = 24+ months, and the other patient had
      squamous cell histology (EGFR wild-type), TTF = 7.4 months. In addition, three of
      20 patients (15%) achieved stable disease (SD) >=6 six months (one of whom had
      wild-type EGFR and squamous cell histology, and two patients had an EGFR TKI
      sensitive mutation, one of whom had failed prior erlotinib therapy). Combination
      therapy with ertotinib plus cetuximab was well tolerated. The most common
      toxicities were rash, diarrhea, and hypomagnesemia. The recommended phase II dose
      was erlotinib 150 mg oral daily and cetuximab 250 mg/m(2) i.v. weekly. In
      summary, erlotinib and cetuximab treatment was associated with SD >= six
      months/PR in five of 20 patients with non-small cell lung cancer (25%), including
      individuals with squamous histology, TKI-resistant EGFR mutations, and wild-type
      EGFR, and those who had progressed on prior erlotinib after an initial response.
      This combination warrants further study in select populations of non-small cell
      lung cancer.

PMID- 23963362
TI  - Molecular radiotherapy using cleavable radioimmunoconjugates that target EGFR and
      gammaH2AX.
AB  - Many anticancer therapies, including ionizing radiation (IR), cause cytotoxicity
      through generation of DNA double-strand breaks (DSB). Delivery of therapeutic
      radionuclides to DNA DSB sites can amplify this DNA damage, for additional
      therapeutic gain. Herein, we report on two radiopharmaceuticals, radiolabeled
      with the Auger electron emitter (111)In, with dual specificity for both the
      intranuclear, DNA damage repair signaling protein gammaH2AX and the EGF receptor
      (EGFR). The EGFR ligand EGF was conjugated to a fluorophore- or (111)In-labeled
      anti-gammaH2AX antibody, linked via a nuclear localization sequence (NLS) to
      ensure nuclear translocation. EGF conjugation was achieved either through a
      noncleavable PEG linker (PEO6) or a cleavable disulfide bond. Both conjugates
      selectively bound EGFR on fixed cells and gammaH2AX in cell extracts. Both
      compounds enter EGFR-expressing cells in an EGF/EGFR-dependent manner. However,
      only the cleavable compound was seen to associate with gammaH2AX foci in the
      nuclei of irradiated cells. Intracellular retention of the cleavable compound was
      prolonged in gammaH2AX-expressing cells. Clonogenic survival was significantly
      reduced when cells were exposed to IR (to induce gammaH2AX) plus (111)In-labeled
      cleavable compound compared to either alone and compared to nonspecific controls.
      In vivo, uptake of (111)In-labeled cleavable compound in MDA-MB-468 xenografts in
      athymic mice was 2.57 +/- 0.47 percent injected dose/g (%ID/g) but increased
      significantly to 6.30 +/- 1.47%ID/g in xenografts where gammaH2AX was induced by
      IR (P < 0.01). This uptake was dependent on EGF/EGFR and anti-gammaH2AX/gammaH2AX
      interactions. We conclude that tumor-specific delivery of radiolabeled antibodies
      directed against intranuclear epitopes is possible using cleavable antibody
      peptide conjugates.

PMID- 23963361
TI  - Novel treatment for mantle cell lymphoma including therapy-resistant tumor by NF
      kappaB and mTOR dual-targeting approach.
AB  - Mantle cell lymphoma (MCL) is one of the most aggressive B-cell non-Hodgkin
      lymphomas with a median survival of approximately five years. Currently, there is
      no curative therapy available for refractory MCL because of relapse from therapy
      resistant tumor cells. The NF-kappaB and mTOR pathways are constitutively active
      in refractory MCL leading to increased proliferation and survival. Targeting
      these pathways is an ideal strategy to improve therapy for refractory MCL.
      Therefore, we investigated the in vitro and in vivo antilymphoma activity and
      associated molecular mechanism of action of a novel compound, 13-197, a
      quinoxaline analog that specifically perturbs IkappaB kinase (IKK) beta, a key
      regulator of the NF-kappaB pathway. 13-197 decreased the proliferation and
      induced apoptosis in MCL cells including therapy-resistant cells compared with
      control cells. Furthermore, we observed downregulation of IkappaBalpha
      phosphorylation and inhibition of NF-kappaB nuclear translocation by 13-197 in
      MCL cells. In addition, NF-kappaB-regulated genes such as cyclin D1, Bcl-XL, and
      Mcl-1 were downregulated in 13-197-treated cells. In addition, 13-197 inhibited
      the phosphorylation of S6K and 4E-BP1, the downstream molecules of mTOR pathway
      that are also activated in refractory MCL. Further, 13-197 reduced the tumor
      burden in vivo in the kidney, liver, and lungs of therapy-resistant MCL-bearing
      nonobese diabetic severe-combined immunodeficient (NOD/SCID) mice compared with
      vehicle-treated mice; indeed, 13-197 significantly increased the survival of MCL
      transplanted mice. Together, results suggest that 13-197 as a single agent
      disrupts the NF-kappaB and mTOR pathways leading to suppression of proliferation
      and increased apoptosis in malignant MCL cells including reduction in tumor
      burden in mice.

PMID- 23963363
TI  - Single Particle Orientation and Rotational Tracking (SPORT) in biophysical
      studies.
AB  - The single particle orientation and rotational tracking (SPORT) techniques have
      seen rapid development in the past 5 years. Recent technical advances have
      greatly expanded the applicability of SPORT in biophysical studies. In this
      feature article, we survey the current development of SPORT and discuss its
      potential applications in biophysics, including cellular membrane processes and
      intracellular transport. 

PMID- 23963364
TI  - Mouse models to study the effect of cardiovascular risk factors on brain
      structure and cognition.
AB  - Recent clinical data indicates that hemodynamic changes caused by cardiovascular
      diseases such as atherosclerosis, heart failure, and hypertension affect
      cognition. Yet, the underlying mechanisms of the resulting vascular cognitive
      impairment (VCI) are poorly understood. One reason for the lack of mechanistic
      insights in VCI is that research in dementia primarily focused on Alzheimer's
      disease models. To fill in this gap, we critically reviewed the published data
      and various models of VCI. Typical findings in VCI include reduced cerebral
      perfusion, blood-brain barrier alterations, white matter lesions, and cognitive
      deficits, which have also been reported in different cardiovascular mouse models.
      However, the tests performed are incomplete and differ between models, hampering
      a direct comparison between models and studies. Nevertheless, from the currently
      available data we conclude that a few existing surgical animal models show the
      key features of vascular cognitive decline, with the bilateral common carotid
      artery stenosis hypoperfusion mouse model as the most promising model. The
      transverse aortic constriction and myocardial infarction models may be good
      alternatives, but these models are as yet less characterized regarding the
      possible cerebral changes. Mixed models could be used to study the combined
      effects of different cardiovascular diseases on the deterioration of cognition
      during aging. 

PMID- 23963366
TI  - PKC-beta exacerbates in vitro brain barrier damage in hyperglycemic settings via
      regulation of RhoA/Rho-kinase/MLC2 pathway.
AB  - Stroke patients with hyperglycemia (HG) develop higher volumes of brain edema
      emerging from disruption of blood-brain barrier (BBB). This study explored
      whether inductions of protein kinase C-beta (PKC-beta) and RhoA/Rho-kinase/myosin
      regulatory light chain-2 (MLC2) pathway may account for HG-induced barrier damage
      using an in vitro model of human BBB comprising human brain microvascular
      endothelial cells (HBMEC) and astrocytes. Hyperglycemia (25 mmol/L D-glucose)
      markedly increased RhoA/Rho-kinase protein expressions (in-cell westerns), MLC2
      phosphorylation (immunoblotting), and PKC-beta (PepTag assay) and RhoA (Rhotekin
      binding assay) activities in HBMEC while concurrently reducing the expression of
      tight junction protein occludin. Hyperglycemia-evoked in vitro barrier
      dysfunction, confirmed by decreases in transendothelial electrical resistance and
      concomitant increases in paracellular flux of Evan's blue-labeled albumin, was
      accompanied by malformations of actin cytoskeleton and tight junctions.
      Suppression of RhoA and Rho-kinase activities by anti-RhoA immunoglobulin G (IgG)
      electroporation and Y-27632, respectively prevented morphologic changes and
      restored plasma membrane localization of occludin. Normalization of glucose
      levels and silencing PKC-beta activity neutralized the effects of HG on occludin
      and RhoA/Rho-kinase/MLC2 expression, localization, and activity and consequently
      improved in vitro barrier integrity and function. These results suggest that HG
      induced exacerbation of the BBB breakdown after an ischemic stroke is mediated in
      large part by activation of PKC-beta. 

PMID- 23963365
TI  - Netrin-1 overexpression promotes white matter repairing and remodeling after
      focal cerebral ischemia in mice.
AB  - Damage of oligodendrocytes after ischemia has negative impact on white matter
      integrity and neuronal function. In this work, we explore whether Netrin-1 (NT-1)
      overexpression facilitates white matter repairing and remodeling. Adult CD-1 mice
      received stereotactic injection of adeno-associated virus carrying NT-1 gene (AAV
      NT-1). One week after gene transfer, mice underwent 60 minutes of middle cerebral
      artery occlusion. The effect of NT-1 on neural function was evaluated by
      neurobehavioral tests. Proliferated oligodendrocyte progenitor cells (OPCs),
      newly matured oligodendrocytes, and remyelination were semi-quantified by
      immunohistochemistry. The role of NT-1 in oligodendrogenesis was further explored
      by examining specific NT-1 receptors and their function. Netrin-1 overexpression
      was detected in neurons and astrocytes 2 weeks after AAV-NT-1 gene transfer and
      significantly improved the neurobehavioral outcomes compared with the control
      (P<0.05). In comparison with the control, proliferated OPCs, newly matured
      oligodendrocytes, and remyelination were greatly increased in the ipsilateral
      hemisphere of AAV-NT-1-transduced mice. Furthermore, both NT-1 receptors deleted
      in colorectal carcinoma and UNC5H2 were expressed on OPCs whereas only UNC5H2 was
      expressed in myelinated axons. Our study indicated that NT-1 promoted OPC
      proliferation, differentiation, and increased remyelination, suggesting that NT-1
      is a promising factor for white matter repairing and remodeling after ischemia. 

PMID- 23963367
TI  - Cerebral extracellular lactate increase is predominantly nonischemic in patients
      with severe traumatic brain injury.
AB  - Growing evidence suggests that endogenous lactate is an important substrate for
      neurons. This study aimed to examine cerebral lactate metabolism and its
      relationship with brain perfusion in patients with severe traumatic brain injury
      (TBI). A prospective cohort of 24 patients with severe TBI monitored with
      cerebral microdialysis (CMD) and brain tissue oxygen tension (PbtO2) was studied.
      Brain lactate metabolism was assessed by quantification of elevated CMD lactate
      samples (>4 mmol/L); these were matched to CMD pyruvate and PbtO2 values and
      dichotomized as glycolytic (CMD pyruvate >119 MUmol/L vs. low pyruvate) and
      hypoxic (PbtO2 <20 mm Hg vs. nonhypoxic). Using perfusion computed tomography
      (CT), brain perfusion was categorized as oligemic, normal, or hyperemic, and was
      compared with CMD and PbtO2 data. Samples with elevated CMD lactate were
      frequently observed (41+/-8%), and we found that brain lactate elevations were
      predominantly associated with glycolysis and normal PbtO2 (73+/-8%) rather than
      brain hypoxia (14+/-6%). Furthermore, glycolytic lactate was always associated
      with normal or hyperemic brain perfusion, whereas all episodes with hypoxic
      lactate were associated with diffuse oligemia. Our findings suggest predominant
      nonischemic cerebral extracellular lactate release after TBI and support the
      concept that lactate may be used as an energy substrate by the injured human
      brain. 

PMID- 23963368
TI  - Alteplase treatment does not increase brain injury after mechanical middle
      cerebral artery occlusion in the rat.
AB  - Recanalization of an occluded vessel with recombinant tissue plasminogen
      activator is an effective strategy for treating acute ischemic stroke.
      Recombinant tissue plasminogen activator is administered as alteplase, a
      formulation containing many excipients including L-arginine, the substrate for
      nitric oxide production. Most studies fail to compare the effects of alteplase on
      brain injury to its L-arginine carrier solution. This study aimed to verify the
      previously reported detrimental effects of alteplase after cerebral ischemia and
      delineate the contribution of L-arginine. Male Wistar rats, subjected to 90
      minutes of intraluminal middle cerebral artery occlusion (MCAO), were
      administered alteplase, the carrier solution or saline upon reperfusion. Neither
      alteplase nor the carrier affected cerebral blood flow (CBF) restoration
      throughout the first 60 minutes of reperfusion. Alteplase treatment was
      associated with increased mortality after MCAO. Twenty-four hours after MCAO,
      neurologic function and infarct volume did not differ between rats treated with
      alteplase, the carrier solution, or saline. Irrespective of treatment group,
      infarct volume was correlated with CBF during reperfusion, neuroscore, and peri
      infarct depolarizations. These results suggest that alteplase treatment,
      independent of thrombolysis, does not cause increased ischemic injury compared
      with its appropriate carrier solution, supporting the continued use of alteplase
      in eligible ischemic stroke patients. 

PMID- 23963369
TI  - Contributions of degradation and brain-to-blood elimination across the blood
      brain barrier to cerebral clearance of human amyloid-beta peptide(1-40) in mouse
      brain.
AB  - The purpose of the present study was to estimate the relative contributions of
      degradation and brain-to-blood elimination processes to the clearance of
      microinjected human amyloid-beta peptide(1-40) (hAbeta(1-40)) from mouse cerebral
      cortex, using a solid-phase extraction method together with a newly developed
      ultraperformance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS)
      quantitation method for intact hAbeta(1-40). The clearance rate constant of
      hAbeta(1-40) in mouse cerebral cortex was determined to be 3.21 * 10(-2)/min
      under conditions where the saturable brain-to-blood elimination process across
      the blood-brain barrier (BBB) was expected to be saturated. Thus, this clearance
      rate constant should mainly reflect degradation. The [(125)I]hAbeta(1-40)
      elimination rate across the BBB under nonsaturating conditions was determined to
      be 1.48 * 10(-2)/min. Inhibition studies suggested that processes sensitive to
      insulin and phosphoramidon, which inhibit neprilysin, insulin-degrading enzyme,
      and endothelin-converting enzyme, are involved not only in degradation, but also
      in elimination of hAbeta(1-40). In conclusion, our results suggest a dominant
      contribution of degradation to cerebral hAbeta(1-40) clearance, and also indicate
      that a sequential process of degradation and elimination of degradation products
      is involved in cerebral hAbeta(1-40) clearance. 

PMID- 23963370
TI  - Regional correlation between resting state FDG PET and pCASL perfusion MRI.
AB  - To determine how arterial spin labeling (ASL) measured perfusion relates to
      baseline metabolism, we compared resting state cerebral perfusion using pseudo
      continuous ASL and cerebral glucose metabolism using (18)F-FDG PET in 20 normal
      volunteers. Greater regional metabolism relative to perfusion was observed in the
      putamen, orbitofrontal and temporal lobes, whereas perfusion was relatively
      higher in the hippocampus and insula. In a region of interest analysis limited to
      gray matter, the overall mean correlation between perfusion and metabolism across
      voxels was r=0.43 with considerable regional variability. Cross-voxel
      correlations between relative perfusion and metabolism in mean ASL and PET images
      of all 20 subjects were the highest in the striatum (caudate: r=0.78; putamen:
      r=0.81), and the lowest in medial temporal structures (amygdala: r=0.087;
      hippocampus: r=-0.26). Correlations between mean relative perfusion and
      metabolism across 20 subjects were the highest in the striatum (caudate: r=0.76;
      putamen: r=0.58), temporal lobe (r=0.59), and frontal lobe (r=0.52), but very
      poor in all other structures (r<0.3), particularly in caudal structures such as
      the hippocampus (r=-0.0026), amygdala (r=0.18), and insula (r=0.14). Although
      there was good overall correlation between perfusion and glucose metabolism,
      regional variability should be considered when using either ASL or (18)F-FDG PET
      as surrogate markers for neural activity. 

PMID- 23963371
TI  - Systemic administration of exosomes released from mesenchymal stromal cells
      promote functional recovery and neurovascular plasticity after stroke in rats.
AB  - Here, for the first time, we test a novel hypothesis that systemic treatment of
      stroke with exosomes derived from multipotent mesenchymal stromal cells (MSCs)
      promote neurovascular remodeling and functional recovery after stroke in rats.
      Adult male Wistar rats were subjected to 2 hours of middle cerebral artery
      occlusion (MCAo) followed by tail vein injection of 100 MUg protein from MSC
      exosome precipitates or an equal volume of vehicle phosphate-buffered saline
      (PBS) (n=6/group) 24 hours later. Animals were killed at 28 days after stroke and
      histopathology and immunohistochemistry were employed to identify neurite
      remodeling, neurogenesis, and angiogenesis. Systemic administration of MSC
      generated exosomes significantly improved functional recovery in stroke rats
      compared with PBS-treated controls. Axonal density and synaptophysin-positive
      areas were significantly increased along the ischemic boundary zone of the cortex
      and striatum in MCAo rats treated with exosomes compared with PBS control.
      Exosome treatment significantly increased the number of newly formed doublecortin
      (a marker of neuroblasts) and von Willebrand factor (a marker of endothelial
      cells) cells. Our results suggest that intravenous administration of cell-free
      MSC-generated exosomes post stroke improves functional recovery and enhances
      neurite remodeling, neurogenesis, and angiogenesis and represents a novel
      treatment for stroke. 

PMID- 23963373
TI  - Anionic polymerization and polyhomologation: an ideal combination to synthesize
      polyethylene-based block copolymers.
AB  - A novel one-pot methodology combining anionic polymerization and
      polyhomologation, through a "bridge" molecule (BF3OEt2), was developed for the
      synthesis of polyethylene (PE)-based block copolymers. The anionically
      synthesized macroanion reacts with the "bridge" molecule to afford a 3-arm star
      (trimacromolecular borane) which serves as an initiator for the polyhomologation.

PMID- 23963374
TI  - Spin-locking in low-frequency reaction yield detected magnetic resonance.
AB  - The purported effects of weak magnetic fields on various biological systems from
      animal magnetoreception to human health have generated widespread interest and
      sparked much controversy in the past decade. To date the only well established
      mechanism by which the rates and yields of chemical reactions are known to be
      influenced by magnetic fields is the radical pair mechanism, based on the spin
      dependent reactivity of radical pairs. A diagnostic test for the operation of the
      radical pair mechanism was proposed by Henbest et al. [J. Am. Chem. Soc., 2004,
      126, 8102] based on the combined effects of weak static magnetic fields and
      radiofrequency oscillating fields in a reaction yield detected magnetic resonance
      experiment. Here we investigate the effects on radical pair reactions of applying
      relatively strong oscillating fields, both parallel and perpendicular to the
      static field. We demonstrate the importance of understanding the effect of the
      strength of the radiofrequency oscillating field; our experiments demonstrate
      that there is an optimal oscillating field strength above which the observed
      signal decreases in intensity and eventually inverts. We establish the
      correlation between the onset of this effect and the hyperfine structure of the
      radicals involved, and identify the existence of 'overtone' type features
      appearing at multiples of the expected resonance field position. 

PMID- 23963375
TI  - The necessity of using tenaculum for endometrial sampling procedure with pipelle:
      a randomized controlled study.
AB  - OBJECTIVE: To evaluate the use of tenaculum on pain perception of patients and on
      ease of endometrial sampling procedure with a pipelle. METHODS: A randomized
      controlled trial was conducted in 118 patients for assessing pain perception and
      the ease of the procedure. Patients were randomly assigned to group 1 (without
      tenaculum) and group 2 (with tenaculum). Visual analog scale (VAS) was used to
      assess patients' pain at four different times during the process. VAS-3 reflected
      the pain during the procedure. Likert scale was employed by the surgeon to
      measure the ease of the procedure. Main outcome was VAS and the secondary
      outcomes were Likert scale and success rate in obtaining adequate samples of
      endometrial tissue for histopathological diagnosis. RESULTS: Endometrial sampling
      procedure could not be performed only on three patients who belonged to group 1.
      The VAS-3 scores were higher in group 2 than group 1 (p = 0.001). Nullipar
      patients had higher VAS-3 scores than multipars (p = 0.012). VAS-3 did not vary
      in pre-peri-postmenopausal women (p = 0.901). Likert scale was lower in
      postmenopausal women than peri- or pre-menopausal patients (p = 0.020, 0.017,
      respectively). Use of tenaculum was found by logistic regression analysis to be
      an independent risk factor for patients' pain perception (p = 0.0001, RR 31.8, 95
      % CI 8.3-122.4). Inadequate endometrial sampling was reported in 12 patients who
      were all postmenopausal. CONCLUSION: Endometrial sampling procedure without
      tenaculum is feasible and yields less pain perception than with tenaculum.

PMID- 23963372
TI  - Functional hyperemia and mechanisms of neurovascular coupling in the retinal
      vasculature.
AB  - The retinal vasculature supplies cells of the inner and middle layers of the
      retina with oxygen and nutrients. Photic stimulation dilates retinal arterioles
      producing blood flow increases, a response termed functional hyperemia. Despite
      recent advances, the neurovascular coupling mechanisms mediating the functional
      hyperemia response in the retina remain unclear. In this review, the retinal
      functional hyperemia response is described, and the cellular mechanisms that may
      mediate the response are assessed. These neurovascular coupling mechanisms
      include neuronal stimulation of glial cells, leading to the release of vasoactive
      arachidonic acid metabolites onto blood vessels, release of potassium from glial
      cells onto vessels, and production and release of nitric oxide (NO), lactate, and
      adenosine from neurons and glia. The modulation of neurovascular coupling by
      oxygen and NO are described, and changes in functional hyperemia that occur with
      aging and in diabetic retinopathy, glaucoma, and other pathologies, are reviewed.
      Finally, outstanding questions concerning retinal blood flow in health and
      disease are discussed. 

PMID- 23963376
TI  - CT-guided percutaneous pulse-dose radiofrequency for pudendal neuralgia.
AB  - PURPOSE: The purpose of our study was to evaluate the efficacy of computed
      tomography (CT)-guided percutaneous pulse-dose radiofrequency (PDRF) for the
      treatment of chronic pain in patients with pudendal neuralgia (PN) unresponsive
      to conservative approaches. METHODS: From March 2010 to January 2012, 30 patients
      with a diagnosis of PN were prospectively enrolled in the study, 18 women and 12
      men (mean age 47 years). A 20-gauge cannula with a 10-cm length was placed under
      CT guide in the pudendal (Alcock's) canal. After the spindle was removed, a
      radiofrequency needle with a 5-mm active tip was introduced. The appropriate
      needle placement near the pudendal nerve, without an involvement of the vessels,
      was confirmed with an injection of 1-2 ml of contrast agent. PDRF was performed
      with 1,200 pulses at high voltage (45 V) with 20 ms duration followed by 480 ms
      silent phases. RESULTS: Twenty-six patients completed the study. Procedural
      success was achieved in all patients. Mean VAS scores before PDRF was 9 +/- 0.7.
      Patients had a great improvement in pain intensity after 1 week by PDRF (mean VAS
      scores 3.8 +/- 1.7, p < 0.05), with a stabilization of the symptomatology in the
      following months (mean VAS scores 1.5 +/- 1.1 at 6 months by PDRF, p < 0.05) and
      excellent results after 1 year by the procedure (mean VAS scores 1.9 +/- 0.7, p <
      0.05). CONCLUSIONS: In our preliminary experience, CT-guided percutaneous PDRF
      should be recommended for treatment of PN because we evaluated the tolerability
      of this procedure with satisfactory and encouraging results.

PMID- 23963378
TI  - Synthesis of a self-assembled copper(II) metallo-rectangle with a guanosine
      substituted terpyridine.
AB  - The synthesis of a terpyridine-guanosine ligand and its reaction with copper(II)
      to yield a new [2 + 2] metallo-rectangle is reported. The metallo-rectangle was
      characterized by single crystal X-ray diffraction and the structure showed
      significant intramolecular pi-pi stacking interactions between the two
      terpyridine moieties of the molecule. This prompted us to investigate the
      magnetic properties of the new di-copper(II) assembly which displayed
      ferromagnetic interactions in the solid state.

PMID- 23963380
TI  - Bull's eye! Lyme disease awareness.

PMID- 23963379
TI  - "No one said this would be an issue..." Intimacy after ostomy surgery.

PMID- 23963383
TI  - How do new BSN nurses perceive their nursing education?
AB  - OBJECTIVE: The goal was to determine if new bachelor's of science in nursing
      (BSN) nurses perceived their education to be relevant for the current demands of
      the profession. METHODS: The design was nonexperimental, descriptive survey
      research. Data were gathered using a researcher-designed mailed survey. Addresses
      for survey participants, RNs who had graduated with a BSN within 2 years prior to
      June 2012, were obtained from the North Carolina State Board of Nursing. RESULTS:
      This study found that new graduates in the sample perceived their academic
      preparation to be adequate for transitioning into professional practice; however,
      new graduates wish they'd had more opportunities to practice clinical skills
      while in nursing school. Respondents also perceived that some health assessment
      content included in nursing programs may not typically be useful in entry-level
      nursing practice. CONCLUSIONS: Because a large percentage of the sample perceived
      they'd had inadequate clinical practice time, new nurses might not feel
      completely competent with practice-related skills. Employers should take this
      into consideration when structuring orientation programs. Additionally, the
      curricula planners for BSN programs might creatively and strategically consider
      ways to increase or improve the clinical practice opportunities for nursing
      students.

PMID- 23963384
TI  - Vesicant extravasation.

PMID- 23963385
TI  - If we listen, they will come.

PMID- 23963387
TI  - Opening up about postpartum depression.

PMID- 23963388
TI  - Improving adherence to oral anticancer therapy.

PMID- 23963391
TI  - Patient education series. Sprains and strains.

PMID- 23963392
TI  - Don't be embarrassed: taking a sexual health history.

PMID- 23963393
TI  - Antidepressants.

PMID- 23963394
TI  - A closer look at hantaviruses.

PMID- 23963396
TI  - Performing a clinical breast exam.

PMID- 23963398
TI  - The maize leaf lipidome shows multilevel genetic control and high predictive
      value for agronomic traits.
AB  - Although the plant lipidome show an enormous level of structural and functional
      diversity, our knowledge about its genetic control and its connection to whole
      plant phenotypes is very limited. Here, we profiled 563 lipid species with UPLC
      FT-MS in 289 field-grown inbred lines genotyped with 56,110 SNPs. Genome-wide
      association study identified 174 associations for 76 lipids explaining up to
      31.4% of the genetic variance (P-value 8.4 * 10(-18)). Candidate genes were found
      for lipid synthesis, breakdown, transfer, and protection against peroxidation.
      The detected SNP-lipid associations could be grouped into associations with 1)
      individual lipids, 2) lipids from one biochemical class, and 3) lipids from
      several classes, suggesting a multilevel genetic control architecture. We further
      found a strong connection between the lipidome and agronomic traits in field
      evaluated hybrid progeny. A cross-validated prediction model yielded correlations
      of up to 0.78 suggesting that the lipidome accurately predicts agronomic traits
      relevant in hybrid maize breeding.

PMID- 23963400
TI  - Follow-up of ischaemic heart disease in patients with coeliac disease.
AB  - Patients with coeliac disease and myocardial infarction have a more favourable
      atherosclerotic risk factor profile than controls with myocardial infarction
      (MI). Therefore, MI prognosis and treatment may differ according to coeliac
      status. This paper reports on the study of Swedish MI patients with and without
      coeliac disease (equal to villous atrophy; Marsh histopathology stage 3) based on
      duodenal or jejunal biopsy data. We used the Swedish Quality Register
      (SWEDEHEART) to identify individuals with a record of MI from 2005 to 2008 and to
      obtain data on medication, coronary interventions, and clinical and laboratory
      parameters at 6-10 weeks and one year after first MI. One-year mortality and
      coronary interventions were assessed for 430 coeliac patients and 1988 controls.
      For other outcome variables, we compared 42 coeliac patients with MI and 201
      general population controls with MI. Odds ratios (ORs) were calculated by
      logistic regression. The results showed that compared with controls with MI,
      coeliac individuals with MI had significantly higher one-year all-cause mortality
      (OR = 1.43; 95% confidence interval (CI) = 1.04-1.95) but less often underwent a
      percutaneous coronary intervention (OR = 0.77; 95% CI = 0.61-0.96). Coeliac
      patients were more often prescribed warfarin but less often aspirin and statins.
      The readmission rate due to cardiac events in coeliac patients was 15.2% vs.
      12.6% in controls (p-value = 0.69). Other clinical and laboratory parameters were
      similar. We conclude that the follow up of MI does not seem to differ between
      coeliac patients and controls, and is unlikely to explain the excess mortality
      from cardiovascular disease noted in Swedish patients with CD.

PMID- 23963401
TI  - Tissue engineering of a human 3D in vitro tumor test system.
AB  - Cancer is one of the leading causes of death worldwide. Current therapeutic
      strategies are predominantly developed in 2D culture systems, which inadequately
      reflect physiological conditions in vivo. Biological 3D matrices provide cells an
      environment in which cells can self-organize, allowing the study of tissue
      organization and cell differentiation. Such scaffolds can be seeded with a
      mixture of different cell types to study direct 3D cell-cell-interactions. To
      mimic the 3D complexity of cancer tumors, our group has developed a 3D in vitro
      tumor test system. Our 3D tissue test system models the in vivo situation of
      malignant peripheral nerve sheath tumors (MPNSTs), which we established with our
      decellularized porcine jejunal segment derived biological vascularized scaffold
      (BioVaSc). In our model, we reseeded a modified BioVaSc matrix with primary
      fibroblasts, microvascular endothelial cells (mvECs) and the S462 tumor cell
      line. For static culture, the vascular structure of the BioVaSc is removed and
      the remaining scaffold is cut open on one side (Small Intestinal Submucosa SIS
      Muc). The resulting matrix is then fixed between two metal rings (cell crowns).
      Another option is to culture the cell-seeded SIS-Muc in a flow bioreactor system
      that exposes the cells to shear stress. Here, the bioreactor is connected to a
      peristaltic pump in a self-constructed incubator. A computer regulates the
      arterial oxygen and nutrient supply via parameters such as blood pressure,
      temperature, and flow rate. This setup allows for a dynamic culture with either
      pressure-regulated pulsatile or constant flow. In this study, we could
      successfully establish both a static and dynamic 3D culture system for MPNSTs.
      The ability to model cancer tumors in a more natural 3D environment will enable
      the discovery, testing, and validation of future pharmaceuticals in a human-like
      model. 

PMID- 23963402
TI  - Diffusion-limited reactions in crowded  environments: a local density 
      approximation.
AB  - In the real world, diffusion-limited reactions in chemistry and biology mostly
      occur in crowded environments, such as macromolecular complex formation in the
      cell. Despite the paramount importance of such phenomena, theoretical approaches
      still mainly rely on the Smoluchowski theory, only valid in the infinite dilution
      limit. In this paper we introduce a novel theoretical framework to describe the
      encounter rate and the stationary density profiles for encounters between an
      immobilized target and a fluid of interacting spherical particles, valid in the
      local density approximation. A comparison with numerical simulations performed
      for a fluid of hard spheres and square well attractive hard spheres confirms the
      accuracy of our treatment.

PMID- 23963403
TI  - InP/ZnS-graphene oxide and reduced graphene oxide nanocomposites as fascinating
      materials for potential optoelectronic applications.
AB  - Our recent studies on metal-organic nanohybrids based on alkylated graphene oxide
      (GO), reduced alkylated graphene oxide (RGO) and InP/ZnS core/shell quantum dots
      (QDs) are presented. The GO alkylated by octadecylamine (ODA) and the QD bearing
      a dodecane thiol (DDT) ligand are soluble in toluene. The nanocomposite alkylated
      GO-QD (GOQD) is readily formed from the solution mixture. Treatment of the GOQD
      composite with hydrazine affords a reduced-alkylated-GO-QD (RGOQD) composite. The
      structure, morphology, photophysical and electrical properties of GOQDs and
      RGOQDs are studied. The micro-FTIR and Raman studies demonstrate evidence of the
      QD interaction with GO and RGO through facile intercalation of the alkyl chains.
      The field emission scanning electron microscopy (FESEM) and high resolution
      transmission electron microscopy (HRTEM) images of the GOQD composite show heaps
      of large QD aggregates piled underneath the GO sheet. Upon reduction to RGOQDs,
      the QDs become evenly distributed on the graphene bed and the size of the
      clusters significantly decreases. This also facilitates closer proximity of the
      QDs to the graphene domains by altering the optoelectronic properties of the
      RGOQDs. The X-ray photoelectron spectroscopy (XPS) results confirm QDs being
      retained in the composites, though a small elemental composition change takes
      place. The XPS and the fluorescence spectra show the presence of an In(Zn)P alloy
      while the X-ray diffraction (XRD) results show characteristics of the tetragonal
      indium. The photoluminescence (PL) quenching of QDs in GOQD and RGOQD films
      determined by the time correlated single photon counting (TCSPC) experiment
      demonstrates almost complete fluorescence quenching in RGOQDs. The conductance
      studies demonstrate the differences between GOQDs and RGOQDs. Investigation on
      the metal-oxide-semiconductor field-effect transistor (nMOSFET) characteristics
      shows the composite to exhibit p-type channel material properties. The RGOQD
      exhibits much superior electrical conductance as a channel material compared to
      the GOQD due to the close proximity of the QDs in the RGOQD to the graphene
      surface. The transfer characteristics, memory properties, and on/off ratios of
      the devices are determined. A mechanism has been proposed with reference to the
      Fermi energies of the composites estimated from the ultraviolet photoelectron
      spectroscopy (UPS) studies. 

PMID- 23963407
TI  - [1,5]-Brook rearrangement: an overlooked but valuable silyl migration to
      synthesize configurationally defined vinylsilane. The unique steric and
      electronic effects of geminal bis(silane).
AB  - An unusual [1,5]-Brook rearrangement of the lithium alkoxide of geminal
      bis(silyl) homoallylic alcohol is described. The unique steric and electronic
      effects of geminal bis(silane) were found to be crucial for promoting this long
      range silyl migration, as well as for facilitating the subsequent gamma/Z
      selective addition of silyl allyllithium with carbonyl compounds to synthesize
      diverse configurationally defined Z-vinylsilanes. 

PMID- 23963406
TI  - Antenatal maternal mental health as determinant of postpartum depression in a
      population based mother-child cohort (Rhea Study) in Crete, Greece.
AB  - PURPOSE: Antenatal maternal mental health has been identified as an important
      determinant of postpartum depression (PPD). We investigated the occurrence of
      depression both antenatally and postnatally and examined whether maternal trait
      anxiety and depression during pregnancy were associated with PPD at 8 weeks
      postpartum in a prospective mother-child cohort (Rhea Study) in Crete, Greece.
      METHODS: 438 women completed the Edinburgh Postnatal Depression Scale (EPDS) and
      the Trait subscale of the State-Trait Anxiety Inventory (STAI-Trait)
      questionnaires assessing antenatal depression and anxiety, respectively, during
      the third trimester of pregnancy as well as the EPDS at 8 weeks postpartum.
      RESULTS: The prevalence of women with probable depression (EPDS score >=13) was
      16.7 % at 28-32 weeks of pregnancy and 13.0 % at 8 weeks postpartum. A per 5 unit
      increase in the STAI-Trait subscale increased the odds for PPD by 70 % (OR =
      1.70, 95 % CI 1.41, 2.05), whereas a per unit increase in EPDS during pregnancy
      increased the odds for PPD by 27 % (OR = 1.27, 95 % CI 1.19, 1.36). CONCLUSIONS:
      Our findings suggest that antenatal maternal psychological well-being has a
      significant effect on PPD, which might have important implications for early
      detection during pregnancy of women at risk for postpartum depression.

PMID- 23963408
TI  - Oxidant-induced intramolecular triazole formation.
AB  - C3-symmetric ligands carrying a rigid triaminoguanidinium backbone are important
      building blocks for the preparation of supramolecular coordination cages as
      tetrahedra or trigonal bipyramides. Coordination of Eu(III)- or Gd(III)-ions
      leads to 1,2,4-triazole formation, which has been reported only rarely. Using
      Pd(II)-complexes as a model system, this triazole formation could be analyzed in
      more detail. The preparation of Pd(II)-coordination compounds can be easily done
      under stoichiometric control. These complexes could be transformed into 1,2,4
      triazoles using O2 or H2O2 as an oxidation reagent. The steric demand of the PR3
      coligand seems to play a key role in the cyclisation reaction.

PMID- 23963409
TI  - The effect of limited availability of N or water on C allocation to fine roots
      and annual fine root turnover in Alnus incana and Salix viminalis.
AB  - The effect of limited nitrogen (N) or water availability on fine root growth and
      turnover was examined in two deciduous species, Alnus incana L. and Salix
      viminalis L., grown under three different regimes: (i) supply of N and water in
      amounts which would not hamper growth, (ii) limited N supply and (iii) limited
      water supply. Plants were grown outdoors during three seasons in covered and
      buried lysimeters placed in a stand structure and filled with quartz sand.
      Computer-controlled irrigation and fertilization were supplied through drip
      tubes. Production and turnover of fine roots were estimated by combining
      minirhizotron observations and core sampling, or by sequential core sampling.
      Annual turnover rates of fine roots <1 mm (5-6 year(-1)) and 1-2 mm (0.9-2.8
      year(-1)) were not affected by changes in N or water availability. Fine root
      production (<1 mm) differed between Alnus and Salix, and between treatments in
      Salix; i.e., absolute length and biomass production increased in the order: water
      limited < unlimited < N limited. Few treatment effects were detected for fine
      roots 1-2 mm. Proportionally more C was allocated to fine roots (<=2 mm) in N or
      water-limited Salix; 2.7 and 2.3 times the allocation to fine roots in the
      unlimited regime, respectively. Estimated input to soil organic carbon increased
      by ca. 20% at N limitation in Salix. However, future studies on fine root
      decomposition under various environmental conditions are required. Fine root
      growth responses to N or water limitation were less pronounced in Alnus, thus
      indicating species differences caused by N-fixing capacity and slower initial
      growth in Alnus, or higher fine root plasticity in Salix. A similar seasonal
      growth pattern across species and treatments suggested the influence of outer
      stimuli, such as temperature and light. 

PMID- 23963410
TI  - Carbon dynamics of eucalypt seedlings exposed to progressive drought in elevated
      [CO2] and elevated temperature.
AB  - Elevated [CO2] and temperature may alter the drought responses of tree seedling
      growth, photosynthesis, respiration and total non-structural carbohydrate (TNC)
      status depending on drought intensity and duration. Few studies have addressed
      these important climatic interactions or their consequences. We grew Eucalyptus
      globulus Labill. seedlings in two [CO2] concentrations (400 and 640 MUl l(-1))
      and two temperatures (28/17 and 32/21  degrees C) (day/night) in a sun-lit
      glasshouse, and grew them in well-watered conditions or exposed them to two
      drought treatments having undergone different previous water conditions (i.e.,
      rewatered drought and sustained drought). Progressive drought in both drought
      treatments led to similar limitations in growth, photosynthesis and respiration,
      but reductions in TNC concentration were not observed. Elevated [CO2] ameliorated
      the impact of the drought during the moderate drought phase (i.e., Day 63 to Day
      79) by increasing photosynthesis and enhancing leaf and whole-plant TNC content.
      In contrast, elevated temperature exacerbated the impact of the drought during
      the moderate drought phase by reducing photosynthesis, increasing leaf
      respiration and decreasing whole-plant TNC content. Extreme drought (i.e., Day 79
      to Day 103) eliminated [CO2] and temperature effects on plant growth,
      photosynthesis and respiration. The combined effects of elevated [CO2] and
      elevated temperature on moderate drought stressed seedlings were reduced with
      progressive drought, with no sustained effects on growth despite greater whole
      plant TNC content.

PMID- 23963412
TI  - Physical activity and physical fitness in lymphoma patients before, during, and
      after chemotherapy: a prospective longitudinal study.
AB  - Fatigue is a common and distressing symptom in cancer patients, especially in
      lymphoma patients. One hypothesized mechanism in the etiology of fatigue is a
      vicious circle between fatigue, physical inactivity, and deconditioning. However,
      the natural evolution of physical activity and physical fitness over the course
      of treatment is unknown. Therefore, the aim of this longitudinal study was to
      assess fatigue, physical activity, and physical fitness in lymphoma patients
      before, during, and after treatment. Fatigue was measured with the EORTC-QLQ-C30,
      physical activity with an accelerometer, and physical fitness with a maximal
      incremental cycle ergometer test, 6-min walking distance test, and muscle
      strength measurements. Differences between the three measurement moments and
      baseline differences between Hodgkin lymphoma and non-Hodgkin lymphoma, early and
      advanced disease, were analyzed. Twenty-nine patients were included. Functional
      exercise capacity and quadriceps force were impaired before the start of
      treatment (86 +/- 15 and 82 +/- 16 % of predicted value, respectively). Over the
      course of treatment, significant declines were found in hemoglobin, quadriceps
      force, handgrip force, and maximal oxygen uptake, while patients reported more
      fatigue (p values < 0.016). Fatigue was significantly correlated with hemoglobin
      (r = -0.49), physical activity (r = 0.81), and physical functioning (r = -0.44).
      Large interindividual variations were found. The present study partially
      confirmed the hypothesized vicious circle between fatigue, physical inactivity,
      and deconditioning. Further research with larger samples and longer follow-up is
      needed to identify factors associated with individual variation in the evolution
      of fatigue, physical activity, and physical fitness.

PMID- 23963411
TI  - Network clusters analysis based on protein-protein interaction network
      constructed in phosgene-induced acute lung injury.
AB  - PURPOSE: Acute lung injury (ALI) is characterized by impairment in gas exchange
      and/or lung mechanics that leads to hypoxemia with the presence of diffuse
      pulmonary infiltrate. Assessments of lung injury play important roles in the
      development of rational medical countermeasures. The purpose of this study is to
      investigate the molecular mechanisms of phosgene-induced lung injury. METHODS: We
      downloaded the gene expression profile of lung tissue from mice exposed to air or
      phosgene from gene expression omnibus database and identified differentially
      expressed genes (DEGs) in ALI. Furthermore, we constructed a protein-protein
      interaction (PPI) network and identified network clusters. RESULTS: In total, 582
      DEGs were found and 4 network clusters were identified in the constructed PPI
      network. Gene set enrichment analysis found that DEGs were mainly involved in
      mitochondrion organization and biogenesis, mRNA metabolic process, negative
      regulation of transferase activity or catalytic activity, and coenzyme metabolic
      process. Pathways of spliceosome, glutathione metabolism, and cell cycle were
      dysregulated in phosgene-induced ALI. Besides, we identified four genes,
      including F3, Meis1, Pvf, and Cdc6 in network clusters, which may be used as
      biomarkers of phosgene-induced ALI. CONCLUSIONS: Our results revealed biological
      processes and pathways involved in phosgene-induced ALI and may expand
      understandings of phosgene-induced ALI. However, further experiments are needed
      to confirm our findings.

PMID- 23963413
TI  - Maternal and neonatal outcomes of successful Kielland's rotational forceps
      delivery.

PMID- 23963414
TI  - In reply.

PMID- 23963415
TI  - Pregnancy outcomes with weight gain above or below the 2009 Institute of Medicine
      guidelines.

PMID- 23963416
TI  - Pregnancy outcomes with weight gain above or below the 2009 Institute of Medicine
      guidelines.

PMID- 23963417
TI  - In reply.

PMID- 23963422
TI  - ACOG Practice Bulletin No. 138: Inherited thrombophilias in pregnancy.
AB  - Inherited thrombophilias are associated with an increased risk of venous
      thromboembolism and also have been linked to adverse outcomes in pregnancy.
      However, there is limited evidence to guide screening for and management of these
      conditions in pregnancy. The purpose of this document is to review common
      thrombophilias and their association with maternal venous thromboembolism risk
      and adverse pregnancy outcomes, indications for screening to detect these
      conditions, and management options in pregnancy.

PMID- 23963423
TI  - Committee Opinion No. 571: Solutions for surgical preparation of the vagina.
AB  - Currently, only povidone-iodine preparations are approved for vaginal surgical
      site antisepsis. However, there are compelling reasons to consider chlorhexidine
      gluconate solutions for off-label use in surgical preparation of the vagina,
      especially in women with allergies to iodine. Although chlorhexidine gluconate
      solutions with high concentrations of alcohol are contraindicated for surgical
      preparation of the vagina, solutions with low concentrations of alcohol (eg, 4%)
      are both safe and effective for off-label use as vaginal surgical preparations
      and may be used as an alternative to iodine-based preparations in cases of
      allergy or when preferred by the surgeon.

PMID- 23963424
TI  - Committee Opinion No. 572: Reproductive health care for adolescents with human
      immunodeficiency virus.
AB  - Adolescents make up an increasing percentage of the U.S. population with human
      immunodeficiency virus (HIV). Adolescent-focused care is critical to identify and
      reduce at-risk behavior, comorbidities, and partner transmission. Optimal medical
      and reproductive health care, both now and in the future, with an adolescent
      focused approach, are important for HIV-infected adolescents. Adolescents who are
      infected with HIV should receive care that allows them to realize their sexual
      and reproductive goals while maximizing their personal health and minimizing the
      risk of unintended pregnancy, acquisition of new sexually transmitted infections,
      and transmission of infection to partners or offspring. Key strategies for
      preventing the spread of infection include, early diagnosis, guideline-based
      treatment, and partner notification of HIV status. 

PMID- 23963425
TI  - Committee Opinion No. 573: Magnesium sulfate use in obstetrics.
AB  - The U.S. Food and Drug Administration advises against the use of magnesium
      sulfate injections for more than 5-7 days to stop preterm labor in pregnant
      women. Based on this, the drug classification was changed from Category A to
      Category D, and the labeling was changed to include this new warning information.
      However, the U.S. Food and Drug Administration's change in classification
      addresses an unindicated and nonstandard use of magnesium sulfate in obstetric
      care. The American College of Obstetricians and Gynecologists and the Society for
      Maternal-Fetal Medicine continue to support the short-term (usually less than 48
      hours) use of magnesium sulfate in obstetric care for appropriate conditions and
      for appropriate durations of treatment, which includes the prevention and
      treatment of seizures in women with preeclampsia or eclampsia, fetal
      neuroprotection before anticipated early preterm (less than 32 weeks of
      gestation) delivery, and short-term prolongation of pregnancy (up to 48 hours) to
      allow for the administration of antenatal corticosteroids in pregnant women
      between 24 weeks of gestation and 34 weeks of gestation who are at risk of
      preterm delivery within 7 days.

PMID- 23963426
TI  - Committee Opinion No. 574: Marriage equality for same-sex couples.
AB  - Same-sex couples encounter barriers to health care that include concerns about
      confidentiality and disclosure, stigma and discriminatory attitudes and
      treatment, limited access to health care and health insurance, and often a
      limited understanding of their health risks. Same-sex couples and their families
      are adversely affected by the lack of legal recognition of their relationships, a
      problem with major implications for the health of same-sex couples and their
      families. Tangible harm has come from the lack of financial and health care
      protections granted to legal spouses, and children are harmed by the lack of
      protections afforded to families in which partners are married. However, the
      recent Supreme Court ruling, The United States v Windsor, which afforded equal
      treatment for legally married same-sex couples will provide many important health
      and financial benefits. Evidence suggests that marriage confers health benefits
      to individuals and families, yet a sizable proportion of individuals do not
      experience these health benefits because of their sexual orientation. Additional
      data suggest that same-sex couples who live in states with bans on same-sex
      unions experience adverse health outcomes. Civil marriage is currently available
      to same-sex couples in only thirteen states and the District of Columbia and
      honored by one state. The American College of Obstetricians and Gynecologists
      endorses marriage equality for same-sex couples and equal treatment for these
      couples and their families and applauds the Supreme Court's decision as an
      important step in improving access to benefits received by legally married same
      sex couples. However, additional efforts are necessary to ensure that same-sex
      couples in every state can receive these same benefits.

PMID- 23963428
TI  - Anomalous switching in Nb/Ru/Sr2RuO4 topological junctions by chiral domain wall
      motion.
AB  - A spontaneous symmetry breaking in a system often results in domain wall
      formation. The motion of such domain walls is utilized to realize novel devices
      like racetrack-memories, in which moving ferromagnetic domain walls store and
      carry information. Superconductors breaking time reversal symmetry can also form
      domains with degenerate chirality of their superconducting order parameter.
      Sr2RuO4 is the leading candidate of a chiral p-wave superconductor, expected to
      be accompanied by chiral domain structure. Here, we present that Nb/Ru/Sr2RuO4
      topological superconducting-junctions, with which the phase winding of order
      parameter can be effectively probed by making use of real-space topology, exhibit
      unusual switching between higher and lower critical current states. This
      switching is well explained by chiral-domain-wall dynamics. The switching can be
      partly controlled by external parameters such as temperature, magnetic field and
      current. These results open up a possibility to utilize the superconducting
      chiral domain wall motion for future novel superconducting devices.

PMID- 23963429
TI  - Targeted therapies in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic, multisystem disorder
      characterised by loss of tolerance to endogenous nuclear antigens and
      autoantibody formation. Recent insight into the immunopathogenesis of lupus has
      provided the foundation for a novel class of agents which target specific,
      dysregulated components of the immune system. Efforts have focused predominantly
      on B-cell depleting therapies, of which belimumab was the first to demonstrate
      success in phase III studies and thus receive marketing authorisation. Off-label
      prescribing of rituximab in refractory cases is common and supported by
      uncontrolled studies, which suggest a favourable risk:benefit profile. However,
      two placebo-controlled trials failed to show benefit, possibly because of
      inappropriate patient selection and other aspects of trial methodology.
      Inhibition of dysregulated co-stimulatory signals and cytokines are other
      therapeutic strategies currently under investigation. Some candidate drugs failed
      to meet primary endpoints in early-phase clinical trials, yet demonstrated
      clinical benefit when alternative assessment criteria were applied or specific
      patient sub-groups analysed. Well-designed studies of greater size and duration
      are needed to clarify the therapeutic utility of these agents. Future
      immunomodulatory strategies targeting interferon-alpha, T cells, oxidative stress
      and epigenetic abnormalities may reduce multisystem disease activity and prolong
      survival in this complex and heterogeneic disease.

PMID- 23963430
TI  - Impaired sexual function in women with systemic lupus erythematosus: a cross
      sectional study.
AB  - OBJECTIVE: The objectives of this paper are to compare sexual function and
      distress in women with systemic lupus erythematosus (SLE) and in healthy
      controls; to determine the association between disease characteristics, quality
      of life, psychopathology and sexual function; and to compare sexual function and
      distress of women according to age (reproductive and nonreproductive-age women).
      METHODS: We conducted a cross-sectional study of 120 participants; 65 women had
      SLE (aged 18-65), and 55 were healthy, age-matched controls. The assessment
      included the Female Sexual Function Index (FSFI), Symptom Checklist-90-Revised
      (SCL-90-R), Short Form 36 health survey (SF-36), socio-demographic
      characteristics and the Systemic Lupus International Collaborating Clinics
      (SLICC) and SLE Disease Activity Index (SLEDAI) in SLE patients only. RESULTS: Of
      65 eligible patients with SLE, 61 (94%) responded; of 55 control subjects, 53
      (96%) responded. The FSFI total score and subscale scores for desire, arousal,
      lubrication, orgasm and pain were significantly lower in patients with SLE. More
      somatization, obsessive-compulsive symptoms, interpersonal sensitivity,
      depression, anxiety, hostility, phobia, paranoid ideation, psychoticism, the
      Positive Symptom Total (PST), Positive Score Discomfort Index (PSDI), the use of
      psychotropic drugs, general health, vitality, social function, emotional role and
      mental health were significantly associated with changes in the patient group's
      sexuality. Multivariate analysis indicated that depression, PSDI and vitality
      were the variables significantly associated with low sexual function in patients
      with SLE. CONCLUSIONS: Women with SLE reported significantly impaired sexual
      function compared with healthy controls. Impaired sexual function was associated
      with somatization, obsessive-compulsive behavior, interpersonal sensitivity,
      depression, hostility, paranoid ideation, psychoticism, PST, higher scores in the
      PSDI subscale, vitality, social functioning and mental health. These results
      indicate that, in daily practice, inquiring about sexuality and quality of life
      and screening for psychopathology are important for every patient with SLE,
      irrespective of their clinical characteristics.

PMID- 23963431
TI  - Q222R polymorphism in DNAse I gene is a risk factor for nephritis in South Indian
      SLE patients.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is a multisystem disorder in which
      defective apoptotic clearance is considered to be an important factor in
      pathogenesis. DNAse I is associated with disposal of apoptotic nuclear debris.
      The defective enzyme production due to +2373 A to G (Q222R) in exon 8 is reported
      to be a genetic risk factor for SLE. SLE in Indians is reported to be severe.
      There are no genetic studies reported from India which have explored this aspect
      of DNAseI gene. This study aimed to analyze whether Q222R is a susceptibility
      factor for SLE and to study its influence on clinical manifestations and
      autoantibody production in South Indian Tamils. METHOD: Three hundred SLE cases
      (based on ACR 1982 criteria) and 530 age, sex similar and ethnicity matched
      controls were recruited. All the cases and controls were genotyped for DNAse I
      Q222R polymorphism using PCR-RFLP method. RESULTS: DNAse I Q222R polymorphism is
      prevalent in our population. We observed higher frequency of Q/R in patients
      compared with controls (60% vs. 53%). This was found to be a genetic risk for SLE
      susceptibility (p = 0.04, odds ratio 1.5, 95% confidence interval 1-2.1). It also
      conferred a significant risk for development of nephritis (p = 0.007, odds ratio
      1.93, 95% confidence interval 1.2-3.2). CONCLUSION: DNAse I Q222R polymorphism is
      a potential genetic risk factor for SLE in South Indian Tamils. In addition, the
      mutant allele confers a significant risk for lupus nephritis.

PMID- 23963432
TI  - Physician-patient interactions and outcomes in systemic lupus erythematosus
      (SLE): a conceptual model.
AB  - OBJECTIVE: The objective was to develop a conceptual model illustrating the
      relationships between the physician-patient relationship and patient outcomes,
      including health status and regimen satisfaction, in systemic lupus erythematosus
      (SLE). METHODS: This was a cross-sectional survey of a geographically diverse
      sample of adults with SLE in the United States. Patients completed a Web-based
      survey that focused on physician interactions, clinical management, and patient
      outcomes, including patient perception of treatment regimen and health status.
      All survey variables related to physician interactions and patient perceptions of
      their health and satisfaction were evaluated for incorporation into a patient
      centered model using cluster analysis. Structural equation modeling (SEM) was
      conducted to assess the inter-relationships observed among the variables to
      inform the development of a conceptual model of SLE patient-centered care.
      RESULTS: A total of 302 SLE patients completed the survey. The majority of
      patients were female (94.3%) with a mean age of 46 years. The cluster analysis
      resulted in six main factors: 1) physician interactions, 2) current health and
      hope, 3) satisfaction with treatment, 4) bedside manner, 5) discussion of lupus
      impacts during physician visits, and 6) steroid treatment. The significant
      relationships among the factors showed that positive physician interactions, such
      as including the patient in treatment decisions, were associated with higher
      satisfaction with treatment regimen and patients feeling that SLE was well
      controlled, a more favorable perception of current health, and being more hopeful
      about future health. Among the components of physician interactions, setting
      goals with patients is particularly important, as this was significantly
      associated with the patient being more hopeful about future health. Being steroid
      free was significantly related to higher treatment satisfaction. CONCLUSION: The
      study findings informed a conceptual model of SLE patient-centered care that may
      be used to create more targeted education programs in the management of SLE, with
      the goal to improve patient outcomes.

PMID- 23963433
TI  - Validation and evaluation of the German Brief Index of Lupus Damage (BILD)--a
      self-reported instrument to record damage in systemic lupus erythematosus.
AB  - INTRODUCTION: Damage is a very important predictor for outcome in systemic lupus
      erythematosus (SLE) and should be routinely documented. Patient-reported
      assessments for damage are rare and neither the Lupus Damage Index Questionnaire
      (LDIQ) nor the Brief Index of Lupus Damage (BILD) is validated in German
      language. Our aim was to validate the BILD in German language and evaluate its
      use as a patient-administered instrument. METHOD: We translated and adapted the
      BILD questionnaire to use it as a self-administered questionnaire for German
      speaking SLE patients. It was applied to SLE outpatients at an academic centre
      and compared to the SLICC/SDI and other lupus outcome parameters. RESULTS: The
      German BILD showed as strong a correlation with the SLICC/SDI as the original
      version of the BILD and a superior correlation compared to the LDIQ. It scored
      significantly higher with an increase of age, disease duration or disease
      activity, with a lower functional status or overall health and a higher
      probability of receiving an incapacity pension. CONCLUSION: The German version of
      the BILD shows a comparable validity to the original BILD with even higher
      correlation to physician-reported damage even when used as a self-administered
      questionnaire. Hence it represents a promising instrument to survey damage in
      clinical routine as well as in clinical and epidemiological studies.

PMID- 23963434
TI  - A sensitive method to quantify senescent cancer cells.
AB  - Human cells do not indefinitely proliferate. Upon external and/or intrinsic cues,
      cells might die or enter a stable cell cycle arrest called senescence. Several
      cellular mechanisms, such as telomere shortening and abnormal expression of
      mitogenic oncogenes, have been shown to cause senescence. Senescence is not
      restricted to normal cells; cancer cells have also been reported to senesce.
      Chemotherapeutical drugs have been shown to induce senescence in cancer cells.
      However, it remains controversial whether senescence prevents or promotes
      tumorigenesis. As it might eventually be patient-specific, a rapid and sensitive
      method to assess senescence in cancer cell will soon be required. To this end,
      the standard beta-galactosidase assay, the currently used method, presents major
      drawbacks: it is time consuming and not sensitive. We propose here a flow
      cytometry-based assay to study senescence on live cells. This assay offers the
      advantage of being rapid, sensitive, and can be coupled to the immunolabeling of
      various cellular markers.

PMID- 23963436
TI  - Bi4Ti3O12 nanofibers-BiOI nanosheets p-n junction: facile synthesis and enhanced
      visible-light photocatalytic activity.
AB  - A novel p-n junction photocatalyst of Bi4Ti3O12 nanofibers-BiOI nanosheets has
      been fabricated through a simple and economical technique of electrospinning
      combined with a successive ionic layer adsorption and reaction (SILAR) process.
      The products are characterized by X-ray diffraction (XRD), scanning electron
      microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), high-resolution
      transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS),
      UV-visible diffuse reflectance spectra (DRS), and photoluminescence (PL)
      spectroscopy. The as-formed Bi4Ti3O12 nanofibers are composed of inter-linked
      nanoparticles of 50-80 nm in size. The thickness of the as-grown BiOI nanosheets
      is about 10 nm and the size of the BiOI nanosheets increases with the SILAR
      cycles. In particular, many {001} facets of BiOI nanosheets are exposed, which is
      favorable to enhance the visible-light photocatalytic activity. The p-n junction
      photocatalyst exhibits enhanced visible-light-driven photocatalytic activity for
      decomposition of rhodamine B (RhB) and phenol. The enhanced photocatalytic
      activity can be attributed to the extended absorption in the visible light region
      resulting from the BiOI nanosheets and the effective separation of photogenerated
      carriers driven by the photo-induced potential difference generated at the
      Bi4Ti3O12-BiOI p-n junction interface. 

PMID- 23963437
TI  - Heterogeneous nucleation and crystal  growth on curved surfaces observed by  real
      space imaging.
AB  - We present a real-space imaging study of homogeneous and heterogeneous crystal
      nucleation and growth in colloidal suspensions of slightly charged and
      polydisperse particles. Heterogeneous crystallization is observed close to curved
      surfaces with radii of curvature, R, in the range from 4 to 40 particle
      diameters, d. Close to a curved surface, we find crystal nucleation and growth to
      be suppressed for R approximately < 10d. For R approximately > 15d, fast crystal
      growth is observed similar to that on a flat wall (R = infinity). We use the
      purely topological method of shortest path rings to determine the orientation of
      the crystal on the length scale of the nearest neighbor distance. Crystal nuclei
      forming close to a curved surface are oriented analogous to crystal growth on a
      flat wall with hexagonal planes parallel to the wall. While the smallest nuclei
      appear to be unaffected by the surface, larger nuclei are found to be suppressed
      for radii of curvature R approximately < 10d. The critical nucleus size in the
      vicinity of a curved surface is found to be about the same as for homogeneous
      nucleation.

PMID- 23963438
TI  - The influence of sprint interval training on body composition, physical and
      metabolic fitness in adolescents and young adults with intellectual disability: a
      randomized controlled trial.
AB  - OBJECTIVE: In this study we evaluated the effect of sprint interval training on
      metabolic and physical fitness in adolescents and young adults with intellectual
      disabilities when compared with continuous aerobic training and no training
      (control). METHODS: Fifty-four persons with intellectual disabilities (age: 17
      (3.0), body mass index: 27.7 (3.7), intelligence quotient: 59 (8.6)) were matched
      based on age, gender and intelligence quotient between sprint interval training
      (n = 17), continuous aerobic training (n = 15) and control (n = 14). Sprint
      interval training was composed of three blocks of 10 minutes at ventilatory
      threshold (blocks 1 and 3: 10 sprint bouts of 15 seconds, followed by 45 seconds
      relative rest; block 2: continuous training) twice a week for 15 weeks.
      Continuous aerobic training was composed of three blocks of 10 minutes continuous
      training. After eight weeks, intensity was increased to 110% of ventilatory
      threshold. The control group did not participate in supervised exercise training.
      Before and after the training period, body composition, physical and metabolic
      fitness were evaluated. RESULTS: Sprint interval training showed a significant
      positive evolution for waist circumference, fat%, systolic blood pressure, lipid
      profile, fasting insulin, homeostasis model assessment of insulin resistance,
      peak VO2, peak Watt, ventilatory threshold, 6-minute walk distance and muscle
      fatigue resistance when compared with no training (P < 0.01). The sprint interval
      training group demonstrated significant improvements for fat%, systolic blood
      pressure, low-density lipoprotein, fasting insulin, peak VO2 and peak power and
      ventilatory threshold (P < 0.01) when compared with continuous aerobic training.
      CONCLUSION: In this study we could observe that sprint interval training has
      stronger beneficial effects on body composition, physical fitness and metabolic
      fitness compared with control. Compared with continuous aerobic training, sprint
      interval training seems to result in better outcome.

PMID- 23963439
TI  - Nutrient concentrations in a Pampasic first order stream with different land uses
      in the surrounding plots (Buenos Aires, Argentina).
AB  - The objective of this study was to assess the effect of land use on nutrient
      concentrations in a Pampasic stream. Soluble reactive phosphorus (SRP)
      concentrations in the stream were higher at a site surrounded by fertilized
      double-cropped wheat/soybeans than at unfertilized soybeans plots. Nitrate and
      SRP concentrations in the stream were lower at sites surrounded by soybeans than
      livestock. It is suggested that crop fertilization and cattle manure increased
      nutrients loads released to the stream. It is suggested that preservation and
      restoration of riparian habitats may benefit water quality by decreasing nutrient
      loads. 

PMID- 23963440
TI  - Occurrence of organochlorine pesticides in surface soils from college school
      yards of Xi'an, China.
AB  - In this study, surface soil samples from 14 representative college school yards
      in Xi'an, the capital city of Shaanxi province, China, were collected and
      analyzed for 21 organochlorine pesticides (OCPs). The total concentrations were
      in the ranges of 0.2-67.0 ng/g. HCHs and DDTs were the most dominant compounds
      among the 21 OCPs, and their concentrations ranged from 0.1-8.5 to 0.1-56.3 ng/g,
      respectively. Source identification analysis indicated that the residues of HCHs
      and DDTs were mostly due to historical use of these chemicals or from other
      source regions. The quality of all the Xi'an college school yard soils except
      sample XAUAT was classified as low pollution by OCPs according to the National
      Environmental Quality Standards for Soils of China (GB15618-1995). 

PMID- 23963441
TI  - The effects of three selected endocrine disrupting chemicals on the fecundity of
      fruit fly, Drosophila melanogaster.
AB  - Bisphenol A (BPA), 4-nonylphenol (4-NP) and 4-tert-octylphenol (4-tert-OP) are
      the endocrine disrupting chemicals (EDCs) that has been shown to exert both toxic
      and biological effects on living organisms. The present study investigated
      effects of environmentally relevant concentrations of BPA, 4-NP and 4-tert-OP
      (0.1, 1 and 10 mg/L) on the fecundity of fruit fly Drosophila melanogaster. In
      the all exposure groups of BPA, 4-NP and 4-tert-OP, it was found a statistically
      significant decrease in mean fecundity as compared to the control groups (p <
      0.05). 

PMID- 23963442
TI  - Effect of arthritis and other rheumatic conditions on employment.

PMID- 23963443
TI  - Epinephrine electro-oxidation highlights fast electrochemistry at the graphite
      basal surface.
AB  - Macroscale and nanoscale measurements of epinephrine electro-oxidation at
      graphite electrodes, with different step edge densities, demonstrate
      unequivocally that the reaction occurs readily at the basal surface, and that
      step edges are not required for molecular electrocatalysis, in contrast to the
      current literature model. 

PMID- 23963444
TI  - NLRP7 or KHDC3L genes and the etiology of molar pregnancies and recurrent
      miscarriage.
AB  - Women with mutation in both alleles of the NLRP7 or C6orf221/KHDC3L genes are
      predisposed to diploid biparental moles, but it has also been suggested that
      mutation in these genes can predispose to diploid androgenetic or triploid moles
      and to other kinds of reproductive wastage. We have investigated the association
      between molar pregnancy and recurrent miscarriages regarding changes in the NLRP7
      and C6orf221/KHDC3L genes. Our study group can be divided into three sub-cohorts:
      (i) women having had at least one molar pregnancy and at least two non-mole
      miscarriages, (ii) women having had recurrent androgenetic hydatidiform moles and
      (iii) women having had one diploid androgenetic hydatidiform mole and a relative
      having had a hydatidiform mole (familial hydatidiform moles). We observed a
      statistically non-significant tendency of non-synonymous variants in NLRP7 to be
      more frequent in women with familial hydatidiform mole and in women with female
      family members with hydatidiform mole or non-mole miscarriage compared with women
      with no family history of mole or miscarriage. However, we did not find any
      unequivocal pathogenic mutations (the term 'unequivocal pathogenic mutations'
      refers to mutations that indubitably have a pathogenic effect on the affected
      woman) in NLRP7 or C6orf221/KHDC3L in any of the women in the study group. This
      indicates that recurrent miscarriages plus hydatidiform mole, recurrent
      androgenetic hydatidiform moles and familial androgenetic hydatidiform moles in
      general do not have the same monogenetic etiology as familiar diploid biparental
      moles. 

PMID- 23963445
TI  - Structure-activity studies of 4-phenyl-substituted 2'-benzoylpyridine
      thiosemicarbazones with potent and selective anti-tumour activity.
AB  - 2'-Benzoylpyridine thiosemicarbazones (BpT) are effective iron chelators and
      display potent anti-proliferative activity against tumour cells. In order to gain
      greater insight into the structure-activity relationships of the BpT chelators,
      ten new analogues containing phenyl substituents at the N4-position of the BpT
      structure were synthesised. Importantly, aromatic substitution at the latter
      position of the BpT scaffold has not been previously explored and these studies
      represent the first attempt to investigate their structure-activity
      relationships. These compounds demonstrated significantly enhanced anti
      proliferative activity compared to the clinically used iron chelator,
      desferrioxamine (DFO). Furthermore, the compounds showed appreciable therapeutic
      indices against cancer cells over normal cells in vitro. Structure-activity
      analysis revealed that electron-donating substituents such as -CH3 and -OCH3
      resulted in greater anti-proliferative activity than electron-withdrawing groups
      such as -Br and -Cl. These findings help to elucidate the effect of a variety of
      4-phenyl substituents on the biological activity of BpT series of chelators and
      facilitate the future development of thiosemicarbazones with improved anti-tumour
      activity. 

PMID- 23963446
TI  - Disruption of ZO-1/claudin-4 interaction in relation to inflammatory responses in
      methotrexate-induced intestinal mucositis.
AB  - PURPOSE: Methotrexate (MTX)-induced intestinal mucositis limits the use of the
      drug. We previously reported that MTX-dependent production of reactive oxygen
      species is an initiating signal leading to neutrophil migration and intestinal
      barrier dysfunction. Moreover, alterations of zonula occludens (ZO)-1, an
      integral component of tight junctions (TJs), contribute to its dysfunction. This
      study aimed to clarify the identity of inflammatory mediators in the intestine of
      MTX-treated rats and to evaluate MTX-stimulated alterations in the expression of
      TJ proteins other than ZO-1 (e.g., occludin and claudins). METHODS: Male Wistar
      rats were administrated MTX (15 mg kg(-1)) orally once daily for 4 days. Tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta, macrophage inflammatory
      protein (MIP)-2, cytokine-induced neutrophil chemoattractant-2, Toll-like
      receptor 4 (TLR4), and occludin were determined by real-time RT-PCR. Expression,
      distribution, and interactions of TJ proteins were evaluated by Western blotting,
      immunohistochemistry, and immunoprecipitation. RESULTS: MTX increased the mRNA
      levels of TNF-alpha, IL-1beta, MIP-2, and TLR4 in the small intestine, as well as
      the protein expression of claudin-2. Increased claudin-2 and decreased claudin-4
      immunostaining were also observed. Occludin mRNA levels were significantly
      diminished by MTX administration, whereas occludin protein levels and the
      interaction between ZO-1 and occludin were unaltered; however, the interaction
      between ZO-1 and claudin-4 was significantly compromised. CONCLUSIONS: These
      results indicate that elevated levels of inflammatory cytokines and chemokines in
      the small intestine of MTX-treated rats may contribute to the inhibition of ZO
      1/claudin-4 binding, and that inhibition of ZO-1/claudin-4 binding may in turn
      lead to a reduction in claudin-4 expression.

PMID- 23963447
TI  - Microfibril-associated glycoprotein 2 (MAGP2) loss of function has pleiotropic
      effects in vivo.
AB  - Microfibril-associated glycoprotein (MAGP) 1 and 2 are evolutionarily related but
      structurally divergent proteins that are components of microfibrils of the
      extracellular matrix. Using mice with a targeted inactivation of Mfap5, the gene
      for MAGP2 protein, we demonstrate that MAGPs have shared as well as unique
      functions in vivo. Mfap5(-/-) mice appear grossly normal, are fertile, and have
      no reduction in life span. Cardiopulmonary development is typical. The animals
      are normotensive and have vascular compliance comparable with age-matched wild
      type mice, which is indicative of normal, functional elastic fibers. Loss of
      MAGP2 alone does not significantly alter bone mass or architecture, and loss of
      MAGP2 in tandem with loss of MAGP1 does not exacerbate MAGP1-dependent
      osteopenia. MAGP2-deficient mice are neutropenic, which contrasts with
      monocytopenia described in MAGP1-deficient animals. This suggests that MAGP1 and
      MAGP2 have discrete functions in hematopoiesis. In the cardiovascular system,
      MAGP1;MAGP2 double knockout mice (Mfap2(-/-);Mfap5(-/-)) show age-dependent
      aortic dilation. These findings indicate that MAGPs have shared primary functions
      in maintaining large vessel integrity. In solid phase binding assays, MAGP2 binds
      active TGFbeta1, TGFbeta2, and BMP2. Together, these data demonstrate that loss
      of MAGP2 expression in vivo has pleiotropic effects potentially related to the
      ability of MAGP2 to regulate growth factors or participate in cell signaling. 

PMID- 23963448
TI  - Transcriptional induction of ADAMTS5 protein by nuclear factor-kappaB (NF-kappaB)
      family member RelA/p65 in chondrocytes during osteoarthritis development.
AB  - Here we sought to identify transcription factors that induce ADAMTS5, a crucial
      proteinase for osteoarthritis development. Exhaustive comparison of the genomic
      sequences of human, macaque, and mouse ADAMTS5 genes revealed that the proximal
      1.4 kb of the 5'-end-flanking regions containing several consensus motifs was
      highly conserved. Among putative transcription factors for these motifs, NF
      kappaB family member RelA/p65 most strongly stimulated the promoter activity. In
      the ADAMTS5 gene, there were three NF-kappaB binding motifs, in which deletion,
      mutagenesis, and tandem repeat analyses of the luciferase assay identified the
      core responsive elements of RelA/p65 to be -896/-887 and -424/-415 bp with
      specific bindings. The endogenous Adamts5 expression in ATDC5 cells was increased
      by RelA/p65 overexpression and decreased by knockdown through its siRNA. The
      expression was also inhibited by the Rela deletion through Cre transfection in
      primary articular chondrocytes from Rela(fl/fl) mice. In the ex vivo culture of
      femoral head cartilage from mesenchymal cell-specific Rela knock-out (Prx1
      Cre;Rela(fl/fl)) mice, aggrecanolysis was significantly lower than that in the
      Rela(fl/fl) cartilage. Finally, in the experimental mouse osteoarthritis model,
      ADAMTS5 and RelA were co-localized in chondrocytes of degraded articular
      cartilage. We conclude that RelA/p65 is a potent transcriptional activator of
      ADAMTS5 in chondrocytes during osteoarthritis development. 

PMID- 23963449
TI  - Homotypic versican G1 domain interactions enhance hyaluronan incorporation into
      fibrillin microfibrils.
AB  - Versican G1 domain-containing fragments (VG1Fs) have been identified in extracts
      from the dermis in which hyaluronan (HA)-versican-fibrillin complexes are found.
      However, the molecular assembly of VG1Fs in the HA-versican-microfibril
      macrocomplex has not yet been elucidated. Here, we clarify the role of VG1Fs in
      the extracellular macrocomplex, specifically in mediating the recruitment of HA
      to microfibrils. Sequential extraction studies suggested that the VG1Fs were not
      associated with dermal elements through HA binding properties alone. Overlay
      analyses of dermal tissue sections using the recombinant versican G1 domain, rVN,
      showed that rVN deposited onto the elastic fiber network. In solid-phase binding
      assays, rVN bound to isolated nondegraded microfibrils. rVN specifically bound to
      authentic versican core protein produced by dermal fibroblasts. Furthermore, rVN
      bound to VG1Fs extracted from the dermis and to nondenatured versican but not to
      fibrillin-1. Homotypic binding of rVN was also seen. Consistent with these
      binding properties, macroaggregates containing VG1Fs were detected in high
      molecular weight fractions of sieved dermal extracts and visualized by electron
      microscopy, which revealed localization to microfibrils at the microscopic level.
      Importantly, exogenous rVN enhanced HA recruitment both to isolated microfibrils
      and to microfibrils in tissue sections in a dose-dependent manner. From these
      data, we propose that cleaved VG1Fs can be recaptured by microfibrils through
      VG1F homotypical interactions to enhance HA recruitment to microfibrils. 

PMID- 23963450
TI  - Cloning and structure-function analyses of quinolone- and acridone-producing
      novel type III polyketide synthases from Citrus microcarpa.
AB  - Two novel type III polyketide synthases, quinolone synthase (QNS) and acridone
      synthase (ACS), were cloned from Citrus microcarpa (Rutaceae). The deduced amino
      acid sequence of C. microcarpa QNS is unique, and it shared only 56-60%
      identities with C. microcarpa ACS, Medicago sativa chalcone synthase (CHS), and
      the previously reported Aegle marmelos QNS. In contrast to the quinolone- and
      acridone-producing A. marmelos QNS, C. microcarpa QNS produces 4-hydroxy-N
      methylquinolone as the "single product" by the one-step condensation of N
      methylanthraniloyl-CoA and malonyl-CoA. However, C. microcarpa ACS shows broad
      substrate specificities and produces not only acridone and quinolone but also
      chalcone, benzophenone, and phloroglucinol from 4-coumaroyl-CoA, benzoyl-CoA, and
      hexanoyl-CoA, respectively. Furthermore, the x-ray crystal structures of C.
      microcarpa QNS and ACS, solved at 2.47- and 2.35-A resolutions, respectively,
      revealed wide active site entrances in both enzymes. The wide active site
      entrances thus provide sufficient space to facilitate the binding of the bulky N
      methylanthraniloyl-CoA within the catalytic centers. However, the active site
      cavity volume of C. microcarpa ACS (760 A(3)) is almost as large as that of M.
      sativa CHS (750 A(3)), and ACS produces acridone by employing an active site
      cavity and catalytic machinery similar to those of CHS. In contrast, the cavity
      of C. microcarpa QNS (290 A(3)) is significantly smaller, which makes this enzyme
      produce the diketide quinolone. These results as well as mutagenesis analyses
      provided the first structural bases for the anthranilate-derived production of
      the quinolone and acridone alkaloid by type III polyketide synthases. 

PMID- 23963451
TI  - Conformational plasticity of the essential membrane-associated
      mannosyltransferase PimA from mycobacteria.
AB  - Phosphatidyl-myo-inositol mannosyltransferase A (PimA) is an essential
      glycosyltransferase (GT) that initiates the biosynthetic pathway of phosphatidyl
      myo-inositol mannosides, lipomannan, and lipoarabinomannan, which are key
      glycolipids/lipoglycans of the mycobacterial cell envelope. PimA belongs to a
      large family of peripheral membrane-associated GTs for which the understanding of
      the molecular mechanism and conformational changes that govern substrate/membrane
      recognition and catalysis remains a major challenge. Here we used single molecule
      force spectroscopy techniques to study the mechanical and conformational
      properties of PimA. In our studies, we engineered a polyprotein containing PimA
      flanked by four copies of the well characterized I27 protein, which provides an
      unambiguous mechanical fingerprint. We found that PimA exhibits weak mechanical
      stability albeit displaying beta-sheet topology expected to unfold at much higher
      forces. Notably, PimA unfolds following heterogeneous multiple step mechanical
      unfolding pathways at low force akin to molten globule states. Interestingly, the
      ab initio low resolution envelopes obtained from small angle x-ray scattering of
      the unliganded PimA and the PimA.GDP complexed forms clearly demonstrate that not
      only the "open" and "closed" conformations of the GT-B enzyme are largely present
      in solution, but in addition, PimA experiences remarkable flexibility that
      undoubtedly corresponds to the N-terminal "Rossmann fold" domain, which has been
      proved to participate in protein-membrane interactions. Based on these results
      and on our previous experimental data, we propose a model wherein the
      conformational transitions are important for the mannosyltransferase to interact
      with the donor and acceptor substrates/membrane. 

PMID- 23963452
TI  - Eukaryotic release factor 3 is required for multiple turnovers of peptide release
      catalysis by eukaryotic release factor 1.
AB  - Eukaryotic peptide release factor 3 (eRF3) is a conserved, essential gene in
      eukaryotes implicated in translation termination. We have systematically measured
      the contribution of eRF3 to the rates of peptide release with both saturating and
      limiting levels of eukaryotic release factor 1 (eRF1). Although eRF3 modestly
      stimulates the absolute rate of peptide release (~5-fold), it strongly increases
      the rate of peptide release when eRF1 is limiting (>20-fold). This effect was
      generalizable across all stop codons and in a variety of contexts. Further
      investigation revealed that eRF1 remains associated with ribosomal complexes
      after peptide release and subunit dissociation and that eRF3 promotes the
      dissociation of eRF1 from these post-termination complexes. These data are
      consistent with models where eRF3 principally affects binding interactions
      between eRF1 and the ribosome, either prior to or subsequent to peptide release.
      A role for eRF3 as an escort for eRF1 into its fully accommodated state is easily
      reconciled with its close sequence similarity to the translational GTPase EFTu. 

PMID- 23963453
TI  - MEKK2 kinase association with 14-3-3 protein regulates activation of c-Jun N
      terminal kinase.
AB  - MEKK2 (MAP/ERK kinase kinase-2) is a serine/threonine kinase that belongs to the
      MEKK/STE11 family of MAP kinase kinase kinases (MAP(3)Ks). MEKK2 integrates
      stress and mitogenic signals to the activation of NF-kappaB, JNK1/2, p38, and
      ERK5 pathways. We have found that MEKK2 is regulated through a phosphorylation
      dependent association with 14-3-3, a group of adapters that modulate dimerization
      and association between proteins. We found that MEKK2 was phosphorylated at Thr
      283, which resulted in decreased activation loop phosphorylation at Ser-519 and
      consequently reduced activity. Mechanistically, we found that MEKK2 associated
      with inactive MEKK2 in the absence of 14-3-3 binding, which led to trans
      autophosphorylation of Ser-519. Enforced binding with 14-3-3 reduced Ser-519
      trans-autophosphorylation. Expression of T283A MEKK2 within a MEKK2(-/-)
      background enhanced stress-activated c-Jun N-terminal kinase activity while
      elevating IL-6 expression, but also reduced ERK activation with a corresponding
      reduced proliferation rate. These results indicate that Thr-283 phosphorylation
      is an important regulatory mechanism for MEKK2 activation. 

PMID- 23963454
TI  - Resorption controls bone anabolism driven by parathyroid hormone (PTH) receptor
      signaling in osteocytes.
AB  - The contribution of remodeling-based bone formation coupled to osteoclast
      activity versus modeling-based bone formation that occurs independently of
      resorption, to the anabolic effect of PTH remains unclear. We addressed this
      question using transgenic mice with activated PTH receptor signaling in
      osteocytes that exhibit increased bone mass and remodeling, recognized skeletal
      effects of PTH elevation. Direct inhibition of bone formation was accomplished
      genetically by overexpressing the Wnt antagonist Sost/sclerostin; and resorption
      dependent bone formation was inhibited pharmacologically with the bisphosphonate
      alendronate. We found that bone formation induced by osteocytic PTH receptor
      signaling on the periosteal surface depends on Wnt signaling but not on
      resorption. In contrast, bone formation on the endocortical surface results from
      a combination of Wnt-driven increased osteoblast number and resorption-dependent
      osteoblast activity. Moreover, elevated osteoclasts and intracortical/calvarial
      porosity is exacerbated by overexpressing Sost and reversed by blocking
      resorption. Furthermore, increased cancellous bone is abolished by Wnt inhibition
      but further increased by blocking resorption. Thus, resorption induced by PTH
      receptor signaling in osteocytes is critical for full anabolism in cortical bone,
      but tempers bone gain in cancellous bone. Dissecting underlying mechanisms of PTH
      receptor signaling would allow targeting actions in different bone compartments,
      enhancing the therapeutic potential of the pathway. 

PMID- 23963455
TI  - Unique N-terminal arm of Mycobacterium tuberculosis PhoP protein plays an unusual
      role in its regulatory function.
AB  - Mycobacterium tuberculosis PhoP, a master regulator involved in complex lipid
      biosynthesis and expression of unknown virulence determinants, is composed of an
      N-terminal receiver domain and a C-terminal effector domain. The two
      experimentally characterized PhoP orthologs, from Escherichia coli and Salmonella
      enterica, display vastly different regulatory capabilities. Here, we demonstrate
      that the 20-residue-long N-terminal arm unique to M. tuberculosis PhoP plays an
      essential role in the expanded regulatory capabilities of this important
      regulator. Although the arm is not required for overall structural stability
      and/or phosphorylation of the PhoP N-domain, strikingly it is essential for
      phosphorylation-coupled transcription regulation of target genes. Consistent with
      this view, arm truncation of PhoP is accompanied by a conformational change of
      the effector domain, presenting a block in activation subsequent to
      phosphorylation. These results suggest that presence of the arm, unique to this
      regulator that shares an otherwise highly conserved domain structure with members
      of the protein family, contributes to the mechanism of inter-domain interactions.
      Thus, we propose that the N-terminal arm is an adaptable structural feature of M.
      tuberculosis PhoP, which evolved to fine-tune regulatory capabilities of the
      transcription factor in response to the changing physiology of the bacilli within
      its host. 

PMID- 23963456
TI  - A cargo-centered perspective on the PEX5 receptor-mediated peroxisomal protein
      import pathway.
AB  - Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and post
      translationally targeted to the organelle by PEX5, the peroxisomal shuttling
      receptor. The pathway followed by PEX5 during this process is known with
      reasonable detail. After recognizing cargo proteins in the cytosol, the receptor
      interacts with the peroxisomal docking/translocation machinery, where it gets
      inserted; PEX5 is then monoubiquitinated, extracted back to the cytosol and,
      finally, deubiquitinated. However, despite this information, the exact step of
      this pathway where cargo proteins are translocated across the organelle membrane
      is still ill-defined. In this work, we used an in vitro import system to
      characterize the translocation mechanism of a matrix protein possessing a type 1
      targeting signal. Our results suggest that translocation of proteins across the
      organelle membrane occurs downstream of a reversible docking step and upstream of
      the first cytosolic ATP-dependent step (i.e. before ubiquitination of PEX5),
      concomitantly with the insertion of the receptor into the docking/translocation
      machinery. 

PMID- 23963457
TI  - Dna2 is involved in CA strand resection and nascent lagging strand completion at
      native yeast telomeres.
AB  - Post-replicational telomere end processing involves both extension by telomerase
      and resection to produce 3'-GT-overhangs that extend beyond the complementary 5'
      CA-rich strand. Resection must be carefully controlled to maintain telomere
      length. At short de novo telomeres generated artificially by HO endonuclease in
      the G2 phase, we show that dna2-defective strains are impaired in both telomere
      elongation and sequential 5'-CA resection. At native telomeres in dna2 mutants,
      GT-overhangs do clearly elongate during late S phase but are shorter than in wild
      type, suggesting a role for Dna2 in 5'-CA resection but also indicating
      significant redundancy with other nucleases. Surprisingly, elimination of Mre11
      nuclease or Exo1, which are complementary to Dna2 in resection of internal double
      strand breaks, does not lead to further shortening of GT-overhangs in dna2
      mutants. A second step in end processing involves filling in of the CA-strand to
      maintain appropriate telomere length. We show that Dna2 is required for normal
      telomeric CA-strand fill-in. Yeast dna2 mutants, like mutants in DNA ligase 1
      (cdc9), accumulate low molecular weight, nascent lagging strand DNA replication
      intermediates at telomeres. Based on this and other results, we propose that FEN1
      is not sufficient and that either Dna2 or Exo1 is required to supplement FEN1 in
      maturing lagging strands at telomeres. Telomeres may be among the subset of
      genomic locations where Dna2 helicase/nuclease is essential for the two-nuclease
      pathway of primer processing on lagging strands. 

PMID- 23963459
TI  - Unique substrate recognition mechanism of the botulinum neurotoxin D light chain.
AB  - Botulinum neurotoxins are the most potent protein toxins in nature. Despite the
      potential to block neurotransmitter release at the neuromuscular junction and
      cause human botulism, they are widely used in protein therapies. Among the seven
      botulinum neurotoxin serotypes, mechanisms of substrate recognition and
      specificity are known to a certain extent in the A, B, E, and F light chains, but
      not in the D light chain (LC/D). In this study, we addressed the unique substrate
      recognition mechanism of LC/D and showed that this serotype underwent hydrophobic
      interactions with VAMP-2 at its V1 motif. The LC/D B3, B4, and B5 binding sites
      specifically recognize the hydrophobic residues in the V1 motif of VAMP-2.
      Interestingly, we identified a novel dual recognition mechanism employed by LC/D
      in recognition of VAMP-2 sites at both the active site and distal binding sites,
      in which one site of VAMP-2 was recognized by two independent, but functionally
      similar LC/D sites that were complementary to each other. The dual recognition
      strategy increases the tolerance of LC/D to mutations and renders it a good
      candidate for engineering to improve its therapeutic properties. In conclusion,
      in this study, we identified a unique multistep substrate recognition mechanism
      by LC/D and provide insights for LC/D engineering and antitoxin development. 

PMID- 23963458
TI  - Loss of phosphatase and tensin homolog (PTEN) induces leptin-mediated leptin gene
      expression: feed-forward loop operating in the lung.
AB  - Elevated levels of systemic and pulmonary leptin are associated with diseases
      related to lung injury and lung cancer. However, the role of leptin in lung
      biology and pathology, including the mechanism of leptin gene expression in the
      pathogenesis of lung diseases, including lung cancer, remains elusive. Here,
      using conditional deletion of tumor suppressor gene Pten in the lung epithelium
      in vivo in transgenic mice and human PTEN-null lung epithelial cells, we identify
      the leptin-driven feed-forward signaling loop in the lung epithelial cells.
      Leptin-mediated leptin/leptin-receptor gene expression likely amplifies leptin
      signaling that may contribute to the pathogenesis and severity of lung diseases,
      resulting in poor clinical outcomes. Loss of Pten in the lung epithelial cells in
      vivo activated adipokine signaling and induced leptin synthesis as ascertained by
      genome-wide mRNA profiling and pathway analysis. Leptin gene transcription was
      mediated by binding of transcription factors NRF-1 and CCAAT/enhancer-binding
      protein delta (C/EBP) to the proximal promoter regions and STAT3 to the distal
      promoter regions as revealed by leptin promoter-mutation, chromatin
      immunoprecipitation, and gain- and loss-of-function studies in lung epithelial
      cells. Leptin treatment induced expression of the leptin/leptin receptor in the
      lung epithelial cells via activation of MEK/ERK, PI3K/AKT/mammalian target of
      rapamycin (mTOR), and JAK2/STAT3 signaling pathways. Expression of constitutively
      active MEK-1, AKT, and STAT3 proteins increased expression, and treatment with
      MEK, PI3K, AKT, and mTOR inhibitors decreased LEP expression, indicating that
      leptin via MAPK/ERK1/2, PI3K/AKT/mTOR, and JAK2/STAT3 pathways, in turn, further
      induces its own gene expression. Thus, targeted inhibition of the leptin-mediated
      feed-forward loop provides a novel rationale for pharmacotherapy of disease
      associated with lung injury and remodeling, including lung cancer. 

PMID- 23963460
TI  - Assessment of drinking water fortification with iron plus ascorbic Acid or
      ascorbic Acid alone in daycare centers as a strategy to control iron-deficiency
      anemia and iron deficiency: a randomized blind clinical study.
AB  - OBJECTIVE: Assess drinking water fortification with iron and/or ascorbic acid as
      a strategy to control iron-deficiency anemia and iron deficiency. METHODS:
      Randomized blind clinical study, fortifying drinking water to 153 pre-school
      children during 3 months, with iron and ascorbic acid (A), ascorbic acid (B) or
      plain water (C). Hemoglobin (Hb), mean corpuscular volume (MCV) and ferritin were
      measured. RESULTS: Within the groups, Hb raised in all three groups, MCV in A and
      B and ferritin in A. The difference between time points 0 and 1 was significant
      between A and B for Hb, when A and B were compared with C for MCV and when A was
      compared with either B or C for ferritin. CONCLUSIONS: Water fortification is
      efficient in controlling iron deficiency and anemia. Iron stores' recovery
      depends on a more effective offer of iron. Water fortification must be preceded
      by a careful assessment of the previous nutritional status.

PMID- 23963461
TI  - "Broadbeam" irradiation of mammalian cells using a vertical microbeam facility.
AB  - A "broadbeam" facility is demonstrated for the vertical microbeam at Surrey's Ion
      Beam Centre, validating the new technique used by Barazzuol et al. (Radiat Res
      177:651-662, 2012). Here, droplets with a diameter of about 4 mm of 15,000
      mammalian cells in suspension were pipetted onto defined locations on a 42-mm
      diameter cell dish with each droplet individually irradiated in "broadbeam" mode
      with 2 MeV protons and 4 MeV alpha particles and assayed for clonogenicity. This
      method enables multiple experimental data points to be rapidly collected from the
      same cell dish. Initially, the Surrey vertical beamline was designed for the
      targeted irradiation of single cells with single counted ions. Here, the benefits
      of both targeted single-cell and broadbeam irradiations being available at the
      same facility are discussed: in particular, high-throughput cell irradiation
      experiments can be conducted on the same system as time-intensive focused-beam
      experiments with the added benefits of fluorescent microscopy, cell recognition
      and time-lapse capabilities. The limitations of the system based on a 2 MV tandem
      accelerator are also discussed, including the uncertainties associated with
      particle Poisson counting statistics, spread of linear energy transfer in the
      nucleus and a timed dose delivery. These uncertainties are calculated with Monte
      Carlo methods. An analysis of how this uncertainty affects relative biological
      effect measurements is made and discussed. 

PMID- 23963464
TI  - A temporary decrease in twitch response following reversal of rocuronium-induced
      neuromuscular block with a small dose of sugammadex in a pediatric patient.
AB  - We report a temporary decrease in twitch response following reversal of
      rocuronium-induced neuromuscular block with a small dose of sugammadex in our
      dose-finding study in pediatric patients. A 19-month-old female infant (9.6 kg,
      80 cm) was scheduled for elective cheiloplasty surgery. Anesthesia was induced
      with nitrous oxide 50% and sevoflurane 5% and maintained with air, oxygen,
      sevoflurane 3%, and fentanyl (total, 3 MUg/kg). Neuromuscular monitoring was
      performed at the adductor pollicis muscle after induction of anesthesia but
      before the administration of rocuronium. Total dose of rocuronium during the
      surgery was 0.9 mg/kg. Neuromuscular block was reversed with 0.5 mg/kg sugammadex
      when one response was observed with post-tetanic count stimulation. Twitch
      responses after sugammadex administration showed a temporary decrease after its
      initial recovery. Maximum decreases in twitch responses were observed 17 min
      after initial dose of sugammadex. Twitch responses recovered to their control
      values after additional doses of 3.5 mg/kg sugammadex (4 mg/kg in total). Time
      from sugammadex administration to maximum decreases in twitch responses is
      earlier than has been reported in adults (20-70 min). It is demonstrated that
      following neuromuscular block reversal with insufficient dose of sugammadex,
      there is a possibility of the recurrence of residual paralysis within less than
      20 min in pediatric patients.

PMID- 23963465
TI  - Use of ROTEM and MEA in a cardiac surgical patient with ITP.

PMID- 23963466
TI  - Multiple sclerosis: basic knowledge and new insights in perioperative management.
AB  - Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous
      system affecting young adults that may lead to significant disability. The
      clinical course varies among the types of the disease as well as among
      individuals. Herein we provide a brief review of the recent data concerning the
      clinical presentation, diagnosis, causes, and pathogenesis of MS as well as
      medication used, followed by the anesthetic considerations of patients diagnosed
      with the disease. To accomplish this, we conducted a systematic PubMed literature
      search for articles, using the terms multiple sclerosis, anesthesia, general,
      regional, perioperative, and preoperative, and we then manually reviewed the
      references from each pertinent article. Because randomized controlled trials on
      the field are rare, most information is derived by case reports and case series.
      We concluded that the disease itself as well as the treatment modalities may have
      several implications in the conduct of anesthesia and perioperative management of
      MS patients. General and regional anesthetic techniques have been successfully
      used. With thorough preoperative evaluation and in depth knowledge of the disease
      and its complications, the MS patients can be managed safely. 

PMID- 23963467
TI  - Coexistence of high performance resistance and capacitance memory based on
      multilayered metal-oxide structures.
AB  - The Au/DyMnO3/Nb:SrTiO3/Au stack was demonstrated to be not only a high
      performance memristor but also a good memcapacitor. The switching time is below
      10 ns, the retention is longer than 10(5) s, and the change ratio of resistance
      (or capacitance) is larger than 100 over the 10(8) switching cycles. Moreover,
      this stack has a broad range of intermediate states that are tunable by the
      operating voltages. It is indicated that the memory effects originate from the
      Nb:SrTiO3/Au junction where the barrier profile is electrically modulated. The
      serial connected Au/DyMnO3/Nb:SrTiO3 stack behaves as a high nonlinear resistor
      paralleling with a capacitor, which raises the capacitance change ratio and
      enhances the memory stability of the device.

PMID- 23963468
TI  - Ischemia-reperfusion model of acute kidney injury and post injury fibrosis in
      mice.
AB  - Ischemia-reperfusion induced acute kidney injury (IR-AKI) is widely used as a
      model of AKI in mice, but results are often quite variable with high, often
      unreported mortality rates that may confound analyses. Bilateral renal pedicle
      clamping is commonly used to induce IR-AKI, but differences between effective
      clamp pressures and/or renal responses to ischemia between kidneys often lead to
      more variable results. In addition, shorter clamp times are known to induce more
      variable tubular injury, and while mice undergoing bilateral injury with longer
      clamp times develop more consistent tubular injury, they often die within the
      first 3 days after injury due to severe renal insufficiency. To improve post
      injury survival and obtain more consistent and predictable results, we have
      developed two models of unilateral ischemia-reperfusion injury followed by
      contralateral nephrectomy. Both surgeries are performed using a dorsal approach,
      reducing surgical stress resulting from ventral laparotomy, commonly used for
      mouse IR-AKI surgeries. For induction of moderate injury BALB/c mice undergo
      unilateral clamping of the renal pedicle for 26 min and also undergo simultaneous
      contralateral nephrectomy. Using this approach, 50-60% of mice develop moderate
      AKI 24 hr after injury but 90-100% of mice survive. To induce more severe AKI,
      BALB/c mice undergo renal pedicle clamping for 30 min followed by contralateral
      nephrectomy 8 days after injury. This allows functional assessment of renal
      recovery after injury with 90-100% survival. Early post-injury tubular damage as
      well as post injury fibrosis are highly consistent using this model.

PMID- 23963469
TI  - A 43-year systematic review and meta-analysis: case-fatality and risk of death
      among adults with tuberculous meningitis in Africa.
AB  - Tuberculous meningitis (TBM) is a preventable and curable common health problem
      among African adults. Poor nutrition, poverty, household crowding, drug resistant
      tuberculosis (TB) strains, AIDS, and malfunctioning TB control programs are
      important risk factors. We conducted a systematic review and meta-analysis of
      published literature reporting case-fatalities of TBM among adults in African
      countries from 1970 till date. A PubMed search identified relevant papers.
      Employed terms include 'adult tuberculous meningitis' AND 'tuberculosis Africa'.
      PRISMA review guidelines were applied. Adult TBM case-fatalities, odds ratio
      (OR), relative risk (RR), forest-plot meta-analysis for weighted OR and RR,
      funnel plots, L'Abbe plots, meta-regressed bubble plots, and inter-study
      homogeneity were computed. Among 15 studies included, adult TBM occurred in up to
      28 % of all meningitis forms with case-fatality of 60 % (inverse-variance
      weighted 54 %). Fixed-effect meta-analysis revealed weighted OR and RR of adult
      TBM fatalities to be 4.37 (95 % CI 3.92, 4.88) and 2.53 (95 % CI 2.38, 2.69),
      respectively. Inter-study homogeneity was reliable, regional representativeness
      was adequate allowing generalizability, and funnel-plots behaved symmetrically
      with insignificant inconsistency. All cases were initiated with anti-TB
      medication, while some had 'breakthrough' TBM. In Africa, adult TBM has a
      significant public health importance with a very high fatality which has remained
      stagnant for the past half-century. This reflects ongoing low quality of medical
      care at facilities where lengthy referrals end up. Community-based studies can
      reveal higher unaccounted morbidity, accrued disability, and larger mortality.
      Improving access points for early TB management at community-level, developing
      health infra-structure for comprehensive case management at facility-level, and
      poverty reduction can help combat this multi-faceted problem--whose reduction can
      in return help fight poverty.

PMID- 23963471
TI  - High-rate repetitive transcranial magnetic stimulation in migraine prophylaxis: a
      randomized, placebo-controlled study.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is an emerging treatment for
      pain but there is no class 1 study on its role in migraine prophylaxis. In this
      study we report the efficacy and safety of high-rate rTMS in migraine
      prophylaxis. Adult migraine patients having >4 attacks/month were randomized to
      high-rate rTMS or sham stimulation. Stimulation in the form of 10 Hz rTMS, 600
      pulses in 10 trains were delivered to the hot spot of the right abductor digiti
      minimi in 412 s. Three sessions were delivered on alternate days. The outcome was
      defined at 1 month. The primary outcome measures were reduction in headache
      frequency and severity >50 % as assessed by the Visual Analogue Scale (VAS). The
      secondary outcome measures were functional disability, rescue medication and
      adverse events. Fifty patients each were randomized to rTMS or sham stimulation.
      The baseline characteristics of rTMS and sham stimulation groups were similar. At
      1 month, headache frequency (78.7 vs. 33.3 %; P = 0.0001) and VAS score (76.6 vs.
      27.1 %; P = 0.0001) improved significantly in the patients receiving rTMS
      compared to those in the sham stimulation group. Functional disability also
      improved significantly in rTMS group (P = 0.0001). Only one patient following
      rTMS developed transient drowsiness and was withdrawn from the study. This study
      provides evidence of the efficacy and safety of 10 Hz rTMS in migraine
      prophylaxis. 

PMID- 23963472
TI  - Theodor Meynert (1833-1892).

PMID- 23963473
TI  - Innominate artery aneurysm after cannulation for extracorporeal membrane
      oxygenation via the right carotid artery.

PMID- 23963470
TI  - The relationship among restless legs syndrome (Willis-Ekbom Disease),
      hypertension, cardiovascular disease, and cerebrovascular disease.
AB  - Untreated sleep disorders may contribute to secondary causes of uncontrolled
      hypertension, cardiovascular disease (CVD), and stroke. Restless legs syndrome,
      or Willis-Ekbom Disease (RLS/WED), is a common sensorimotor disorder with a
      circadian rhythmicity defined by an uncontrollable urge to move the legs that
      worsens during periods of inactivity or at rest in the evening, often resulting
      in sleep disruptions. Sleep disorders such as insomnia and obstructive sleep
      apnea (OSA) are established risk factors for increased risk of hypertension and
      vascular diseases. This literature review outlines the lessons learned from
      studies demonstrating insomnia and OSA as risk factors for hypertension and
      vascular diseases to support the epidemiologic and physiologic evidence
      suggesting a similar increase in hypertension and vascular disease risk due to
      RLS. Understanding the relationships between RLS and hypertension, CVD, and
      stroke has important implications for reducing the risks associated with these
      diseases. 

PMID- 23963474
TI  - Increased serum levels of soluble IL-18 receptor complex in patients with
      allergic asthma.

PMID- 23963475
TI  - Characterization of causative allergens for wheat-dependent exercise-induced
      anaphylaxis sensitized with hydrolyzed wheat proteins in facial soap.
AB  - BACKGROUND: In Japan, hydrolyzed wheat proteins (HWP) have been reported to cause
      wheat-dependent exercise-induced anaphylaxis (WDEIA) by transcutaneous
      sensitization using HWP-containing soap. Patients develop allergic reactions not
      only with soap use, but also with exercise after the intake of wheat protein
      (WP). omega5-Gliadin and HMW-glutenin were identified as major allergens in
      conventional WP-WDEIA patients. However, the allergens in HWP-WDEIA have yet to
      be elucidated. METHODS: Sera were obtained from 22 patients with HWP-sensitized
      WDEIA. The allergenic activities of HWP and six recombinant wheat gluten
      proteins, including alpha/beta-, gamma-, omega1,2- and omega5-gliadin and low-
      and high molecular weight (HMW)-glutenins, were characterized by immunoblot
      analysis and histamine releasing test. IgE-binding epitopes were identified using
      arrays of overlapping peptides synthesized on SPOTs membrane. RESULTS: Immunoblot
      analysis showed that IgE antibodies (Abs) from HWP-WDEIA bound to alpha/beta-,
      gamma- and omega1,2-gliadin. Recombinant gamma-gliadin induced significant
      histamine release from basophils in eight of 11 patients with HWP-WDEIA. An IgE
      binding epitope "QPQQPFPQ" was identified within the primary sequence of gamma
      gliadin, and the deamidated peptide containing the "PEEPFP" sequence bound with
      IgE Abs more strongly compared to the native epitope-peptide. The epitope-peptide
      inhibited IgE-binding to HWP, indicating that the specific IgE to HWP cross
      reacts with gamma-gliadin. CONCLUSIONS: HWP-WDEIA patients could be sensitized to
      HWP containing a PEEPFP sequence, and WDEIA symptoms after WP ingestion could
      partly be induced by gamma-gliadin. These findings could be useful to help
      develop tools for diagnosis and desensitization therapy for HWP-WDEIA.

PMID- 23963477
TI  - Spectroscopy of polycrystalline materials using thinned-substrate planar Goubau
      line at cryogenic temperatures.
AB  - We investigate the effect of substrate thickness on the transmission bandwidth of
      on-chip terahertz-frequency-range planar Goubau lines both experimentally and
      theoretically. The bandwidth and frequency resolution are improved through
      substrate thinning and geometry modifications (reducing reflections arising from
      the THz photoconductive generators and detectors). We demonstrate that the
      enhanced bandwidth (2 THz) and resolution (3.75 GHz) allows this type of on-chip
      waveguide to be used for spectroscopic measurements of polycrystalline materials
      from cryogenic (4 K) to room temperature (292 K) by recording vibrational
      absorption spectra from overlaid samples of lactose monohydrate. 

PMID- 23963476
TI  - Chromogenic detection of Sarin by discolouring decomplexation of a metal
      coordination complex.
AB  - An innovative chromogenic sensing concept based on decomplexation of a tris
      (bipyridine)iron(II) coordination complex has been developed for the detection of
      organophosphorus nerve agents. It was evaluated both on a simulant and real Sarin
      in vapour and liquid phases.

PMID- 23963478
TI  - Conductance and shot noise in strained bilayer graphene.
AB  - We explore the effect of trigonal warping and of elastic deformations on the
      electronic spectrum of bilayer graphene devices, on their ballistic conductance
      as well as on the shot noise. Uniaxial strain distorts the lattice creating a
      uniform fictitious gauge field in the electronic Dirac Hamiltonian which
      ultimately causes a dramatic reconstruction in the trigonally warped electronic
      spectrum, inducing topological transitions in the Fermi surface. In this paper we
      present results of ballistic transport in bilayer graphene in the absence and
      presence of strain, with particular focus on noise and the Fano factor F. The
      inclusion of trigonal warping preserves the pseudo-diffusive value of F = 1/3 at
      the Dirac point, as calculated in the absence of trigonal warping terms. However,
      the range of energies which show pseudo-diffusive transport increases by orders
      of magnitude compared to the results stemming out of a parabolic spectrum and the
      applied strain acts to increase this energy range further. 

PMID- 23963479
TI  - Colorimetric and fluorescent detection of protamines with an anionic
      polythiophene derivative.
AB  - We have developed a novel approach for the colorimetric and fluorescent detection
      of protamines based on an anionic polythiophene derivative. This probe has high
      sensitivity and selectivity toward protamines with a linear detectable range from
      0.1 to 30 MUg mL(-1), and can be used for protamine detection in serum samples. 

PMID- 23963480
TI  - Quantitative analysis of the temperature dependency in Raman active vibrational
      modes of molybdenum disulfide atomic layers.
AB  - Raman spectroscopy is utilized to quantify the temperature dependency of the
      vibrational modes in molybdenum disulfide (MoS2) atomic layers. These analyses
      are essential for understanding the structural properties and phononic behaviors
      of this two-dimensional (2D) material. We quantitatively analyze the temperature
      dependent shifts of the Raman peak positions in the temperature range from 300 to
      550 K, and find that both planar and out-of-plane characteristic modes are highly
      sensitive to temperature variations. This temperature dependency is linear and
      can be fully explained by the first-order temperature coefficient. Using a semi
      quantitative model, we evaluate the contributions of the material's thermal
      expansion and intrinsic temperature effects to this dependency. We reveal that
      the dominating source of shift in the peak position of planar mode E2g(1) for
      samples of all thicknesses investigated is the four-phonon process. In addition
      to the four-phonon process, thermal expansion plays a significant role in the
      temperature dependency of the out-of-plane mode, A1g. The thickness dependency of
      the temperature coefficient for MoS2 and a drastic change in behaviors of samples
      from bi- to single-layered are also demonstrated. We further explore the role of
      defects in the thermal properties of MoS2 by examining the temperature dependency
      of Raman modes in CVD-grown samples. 

PMID- 23963482
TI  - Letter to the Editor concerning "Vertebral rotation in adolescent idiopathic
      scoliosis calculated by radiograph and back surface analysis-based methods:
      correlation between the Raimondi method and rasterstereography".

PMID- 23963483
TI  - Letter to the editor concerning "Hepatic myelopathy with spastic paraparesis:
      report of two cases and review of the literature" by S. Ben Amor et al. (Eur
      Spine J. 2013, Jun 1).

PMID- 23963484
TI  - Letter regarding "Denosumab: a potential new and innovative treatment option for
      aneurysmal bone cysts".

PMID- 23963485
TI  - Answer to the Letter to the Editor of J. Padulo concerning: "Vertebral rotation
      in adolescent idiopathic scoliosis calculated by radiograph and back surface
      analysis-based methods: correlation between the Raimondi method and
      rasterstereography" by Mangone M, Raimondi P, Paoloni M, Pellanera S, Di Michele
      A, Di Renzo S, Vanadia M, Dimaggio M, Murgia M, Santilli V (2013) Eur Spine J
      22:367-371.

PMID- 23963486
TI  - Answer to the letter to the editor of R. Nardone et al. concerning "Hepatic
      myelopathy with spastic paraparesis: report of two cases and review of the
      literature" (by Sana Ben Amor et al. (2013), Eur Spine J; DOI 10.1007/s00586-013
      2828-z).

PMID- 23963487
TI  - Improvement in low back pain following spinal decompression: observational study
      of 119 patients.
AB  - STUDY DESIGN: Prospective clinical observational study of low back pain (LBP) in
      patients undergoing laminectomy or laminotomy surgery for lumbar spinal stenosis
      (LSS). OBJECTIVES: To quantify any change in LBP following laminectomy or
      laminotomy spinal decompression surgery. PATIENTS AND METHODS: 119 patients with
      LSS completed Oswestry Disability Index questionnaire (ODI) and Visual Analogue
      Scale for back and leg pain, preoperatively, 6 weeks and 1 year postoperatively.
      RESULTS: There was significant (p < 0.0001) reduction in mean LBP from a baseline
      of 5.14/10 to 3.03/10 at 6 weeks. Similar results were seen at 1 year where mean
      LBP score was 3.07/10. There was a significant (p < 0.0001) reduction in the mean
      ODI at 6 weeks and 1 year postoperatively. Mean ODI fell from 44.82 to 25.13 at 6
      weeks and 28.39 at 1 year. CONCLUSION: The aim of surgery in patients with LSS is
      to improve the resulting symptoms that include radicular leg pain and
      claudication. This observational study reports statistically significant
      improvement of LBP after LSS surgery. This provides frequency distribution data,
      which can be used to inform prospective patients of the expected outcomes of such
      surgery.

PMID- 23963489
TI  - Low-dose transscleral diode laser cyclophotocoagulation (TSCPC) as a potential
      single treatment for primary open-angle glaucoma (POAG) in Malawi?
AB  - PURPOSE: To investigate if low-dose 810 nm transscleral cyclophotocoagulation
      (TSCPC) can be used as single treatment in Malawian glaucoma patients. METHODS:
      Forty-seven eyes of 28 patients with primary open-angle and pseudoexfoliation
      glaucoma were treated with TSCPC using 12 spots with 900 mW, 2,000 ms (1.8 J per
      spot); six spots in the upper half, six in the lower by sparing the 3 and 9
      o'clock positions +/-20 degrees . Intraocular pressure (IOP) and uncorrected
      visual acuity (UVA) were measured by an independent examiner preoperatively, on
      the first postoperative day, after 2 weeks, and after 3 months. RESULTS: Twenty
      four (86%) and 18 (64%) of 28 patients (31 of 47 eyes; 66%) completed follow-up
      at 2 weeks and at 3 months respectively. After a single treatment session, IOP
      decreased by at least 25 % in 88% (21 of 24) after 2 weeks, and in 50% (nine of
      18) of patients after 3 months. Mean IOP was 38.5 mmHg before TSCPC, 23.5 mmHg (p
      < 0.001) after 1 day, 24.5 mmHg (p < 0.001) after 2 weeks, and 35.6 mmHg (p =
      0.37) after 3 months. In three patients, however, IOP increased after 3 months to
      levels significantly higher than before TSCPC. CONCLUSION: Low-dose TSCPC caused
      a significant IOP lowering for up to 2 weeks (15 mmHg less from baseline) in most
      patients. After 3 months, this effect was stable in 50% of patients; in the other
      half, IOP nearly returned back to baseline.

PMID- 23963490
TI  - Hierarchical assembly of discrete copper(II) metallo-structures from pre
      assembled dinuclear (bis-beta-diketonato)metallocycles and flexible difunctional
      co-ligands.
AB  - The sequential interaction of preformed [Cu2(L1)2(THF)2] (where H2L1 is 1,1-(1,3
      phenylene)-bis(4,4-dimethylpentane-1,3-dione incorporating a 1,3-phenylene linker
      between its two beta-diketone domains) and [Cu2(L4)2].2H2O (where H2L4 is 1,1
      (4,4'-oxybiphenylene)-bis(4,4-dimethylpentane-1,3-dione) incorporating a flexible
      oxybiphenylene linkage between the two beta-diketone groups) with the potentially
      difunctional aliphatic non-planar co-ligands, N-methylpiperazine (mpip), N,N'
      dimethylpiperazine (dmpip) and 1,4-thiomorpholine (thiomorph) is reported. A
      series of extended molecular assemblies exhibiting a range of di- and
      tetranuclear assemblies were obtained and their X-ray structures determined.
      Dinuclear [Cu2(L1)2(mpip)2].2mpip incorporates two 5-coordinate, square pyramidal
      metal centres as does tetranuclear [{Cu2(L1)2}2(dmpip)2].2dmpip. In contrast,
      dinuclear [Cu2(L1)2(dmpip)4].dmpip and [{Cu2(L1)2}2(thiomorph)4].3thiomorph each
      contain two 5-coordinate and two 6-coordinate centres. Each of
      [Cu2(L4)2(THF)2].2THF and Cu2(L4)2(mpip)2].H2O incorporate only 5-coordinate
      metal centres, with the latter complex forming a one-dimensional hydrogen bonded
      ribbon-like structure directed along the crystallographic a-axis. In keeping with
      the documented tendency for the smallest, least strained assembly to form in
      supramolecular self-assembly processes, the incorporation of the flexible "oxy"
      linkage between the 4,4'-linked phenylene rings of H2L3 results in generation of
      a dinuclear [Cu2L2] species rather than a trinuclear (triangular) [Cu3L3] species
      of the type formed by the more rigid bis-beta-diketonato ligand analogue in which
      the biphenylene rings separating the beta-diketone domains are directly coupled
      in their 4,4' positions.

PMID- 23963491
TI  - An effective manual deboning method to prepare intact mouse nasal tissue with
      preserved anatomical organization.
AB  - The mammalian nose is a multi-functional organ with intricate internal
      structures. The nasal cavity is lined with various epithelia such as olfactory,
      respiratory, and squamous epithelia which differ markedly in anatomical
      locations, morphology, and functions. In adult mice, the nose is covered with
      various skull bones, limiting experimental access to internal structures,
      especially those in the posterior such as the main olfactory epithelium (MOE).
      Here we describe an effective method for obtaining almost the entire and intact
      nasal tissues with preserved anatomical organization. Using surgical tools under
      a dissecting microscope, we sequentially remove the skull bones surrounding the
      nasal tissue. This procedure can be performed on both paraformaldehyde-fixed and
      freshly dissected, skinned mouse heads. The entire deboning procedure takes about
      20-30 min, which is significantly shorter than the experimental time required for
      conventional chemical-based decalcification. In addition, we present an easy
      method to remove air bubbles trapped between turbinates, which is critical for
      obtaining intact thin horizontal or coronal or sagittal sections from the nasal
      tissue preparation. Nasal tissue prepared using our method can be used for whole
      mount observation of the entire epithelia, as well as morphological,
      immunocytochemical, RNA in situ hybridization, and physiological studies,
      especially in studies where region-specific examination and comparison are of
      interest.

PMID- 23963492
TI  - The effects of pesticides on bacterial nitrogen fixers in peanut-growing area.
AB  - In the peanut production, the applications of herbicides and fungicides are a
      common practice. In this work, studies done under field conditions demonstrated
      that pesticides affected negatively the number and nitrogenase activity of
      diazotrophic populations of soil. Agrochemical effects were not transient, since
      these parameters were not recovered to pre-treatment levels even 1 year after
      pesticides application. Results obtained from greenhouse experiments revealed
      that the addition of herbicide or fungicides diminished the free-living
      diazotrophs number reaching levels found in soil amended with the pesticides and
      that the number of symbiotic diazotrophs was not affected by the insecticide
      assayed. The soil nitrogenase activity was not affected by fungicides and
      glyphosate. The effect of pesticides on the nitrogen-fixing bacteria diversity
      was evaluated both in field and greenhouse experiments. Analysis of clone
      libraries generated from the amplification of soil nifH gene showed a diminution
      in the genetic diversity of this bacterial community. 

PMID- 23963493
TI  - Role of the aryl hydrocarbon receptor (AhR) in lung inflammation.
AB  - Millions of individuals worldwide are afflicted with acute and chronic
      respiratory diseases, causing temporary and permanent disabilities and even
      death. Oftentimes, these diseases occur as a result of altered immune responses.
      The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor,
      acts as a regulator of mucosal barrier function and may influence immune
      responsiveness in the lungs through changes in gene expression, cell-cell
      adhesion, mucin production, and cytokine expression. This review updates the
      basic immunobiology of the AhR signaling pathway with regards to inflammatory
      lung diseases such as asthma, chronic obstructive pulmonary disease, and
      silicosis following data in rodent models and humans. Finally, we address the
      therapeutic potential of targeting the AhR in regulating inflammation during
      acute and chronic respiratory diseases. 

PMID- 23963495
TI  - Spreading of cooperative behaviour across interdependent groups.
AB  - Recent empirical research has shown that links between groups reinforce
      individuals within groups to adopt cooperative behaviour. Moreover, links between
      networks may induce cascading failures, competitive percolation, or contribute to
      efficient transportation. Here we show that there in fact exists an intermediate
      fraction of links between groups that is optimal for the evolution of cooperation
      in the prisoner's dilemma game. We consider individual groups with regular,
      random, and scale-free topology, and study their different combinations to reveal
      that an intermediate interdependence optimally facilitates the spreading of
      cooperative behaviour between groups. Excessive between-group links simply unify
      the two groups and make them act as one, while too rare between-group links
      preclude a useful information flow between the two groups. Interestingly, we find
      that between-group links are more likely to connect two cooperators than in-group
      links, thus supporting the conclusion that they are of paramount importance. 

PMID- 23963494
TI  - New insights into the aryl hydrocarbon receptor as a modulator of host responses
      to infection.
AB  - The host response to infection is known to be influenced by many factors,
      including genetics, nutritional status, age, as well as drug and chemical
      exposures. Recent advances reveal that the aryl hydrocarbon receptor (AhR)
      modulates aspects of the innate and adaptive immune response to viral, bacterial,
      and parasitic organisms. Although many of these observations were made using the
      high affinity but poorly metabolized AhR agonist 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD), not all of the effects are detrimental to the host. Sometimes AhR
      activation, even with TCDD, was beneficial and improved host resistance and
      survival. A similar dichotomy is observed in infected AhR-deficient mice, wherein
      absence of functional AhR sometimes, but not always, alters host resistance. When
      examined in their totality, current data indicate that AhR controls multiple
      regulatory pathways that converge with infection-associated signals and depending
      on the context (e.g., type of pathogen, site of infection), lead to distinct
      outcomes. This creates numerous exciting opportunities to harness the
      immunomodulatory action of AhR to transform host responses to infection.
      Moreover, since many of the mechanisms cued in response to infectious agents are
      pivotal in the context of other diseases, there is much to be learned about AhR's
      cellular targets and molecular mechanisms of action. 

PMID- 23963496
TI  - Synthesis of phycocyanobilin in mammalian cells.
AB  - The chromophore 3-Z phycocyanobilin (PCB, (2R,3Z)-8,12-bis(2-carboxyethyl)-18
      ethyl-3-ethylidene-2,7,13,17-tetramethyl-2,3-dihydrobilin-1,19(21H,24H)-dione)
      mediates red and far-red light perception in natural and synthetic biological
      systems. Here we describe a PCB synthesis strategy in mammalian cells. We
      optimize the production by co-localizing the biocatalysts to the substrate
      source, by coordinating the availability of the biocatalysts and by reducing the
      degradation of the reaction product. We show that the resulting PCB levels of 2
      MUM are sufficient to sustain the functionality of red light-responsive
      optogenetic tools suitable for the light-inducible control of gene expression in
      mammalian cells.

PMID- 23963497
TI  - Microenterprise development interventions for sexual risk reduction: a systematic
      review.
AB  - Comprehensive interventions that address both individual and structural
      determinants associated with HIV/STI risk are gaining increasing attention over
      the past decade. Microenterprise development offers an appealing model for HIV
      prevention by addressing poverty and gender equality. This study systematically
      reviewed the effects of microenterprise development interventions on HIV/STI
      incidence and sexual risk behaviors. Microenterprise development was defined as
      developing small business capacity among individuals to alleviate poverty. Seven
      eligible research studies representing five interventions were identified and
      included in this review. All of the studies targeted women, and three focused on
      sex workers. None measured biomarker outcomes. All three sex worker studies
      showed significant reduction in sexual risk behaviors when compared to the
      control group. Non-sex worker studies showed limited changes in sexual risk
      behavior. This review indicates the potential utility of microenterprise
      development in HIV risk reduction programs. More research is needed to determine
      how microenterprise development can be effectively incorporated in comprehensive
      HIV control strategies. 

PMID- 23963498
TI  - Reaching men who have sex with men: a comparison of respondent-driven sampling
      and time-location sampling in Guatemala City.
AB  - We present a comparison of respondent-driven sampling (RDS) and time-location
      sampling (TLS) for behavioral surveillance studies among men who have sex with
      men (MSM). In 2010, we conducted two simultaneous studies using TLS (N = 609) and
      RDS (N = 507) in Guatemala city. Differences in characteristics of the population
      reached based on weighted estimates as well as the time and cost of recruitment
      are presented. RDS MSM were marginally more likely to self-report as
      heterosexual, less likely to disclose sexual orientation to family members and
      more likely to report sex with women than TLS MSM. Although RDS MSM were less
      likely than TLS MSM to report >=2 non-commercial male partners, they were more
      likely to report selling sex in the past 12 months. The cost per participant was
      $89 and $121 for RDS and TLS, respectively. Our results suggest that RDS reached
      a more hidden sub-population of non-gay-identifying MSM than TLS and had a lower
      implementation cost.

PMID- 23963499
TI  - Risk of sexually transmitted infections among Mayan women in rural Guatemala
      whose partners are migrant workers.
AB  - HIV and sexually transmitted infection (STI) are of concern in Mayan districts of
      Guatemala in which labor migration is common. This study assessed whether the
      migration status of men is associated with reported STI symptoms among their
      female primary partners. In a multivariate analysis of survey data taken from a
      larger Mayan sexual health study, the odds of reporting STI symptoms were twofold
      higher among women who reported that their partner migrated (OR 2.08, 95 % CI,
      1.16-3.71), compared to women whose partners did not. Women from the Mam and
      Kaqchikel ethnolinguistic groups reported higher rates of STI symptoms after
      adjustment for their partners' migration status. 

PMID- 23963501
TI  - Toward Minimum Standards for Certifying Patient Decision Aids: A Modified Delphi
      Consensus Process.
AB  - OBJECTIVE: The IPDAS Collaboration has developed a checklist and an instrument
      (IPDASi v3.0) to assess the quality of patient decision aids (PDAs) in terms of
      their development process and shared decision-making design components.
      Certification of PDAs is of growing interest in the US and elsewhere. We report a
      modified Delphi consensus process to agree on IPDASi (v3.0) items that should be
      considered as minimum standards for PDA certification, for inclusion in the
      refined IPDASi (v4.0). METHODS: A 2-stage Delphi voting process considered the
      inclusion of IPDASi (v3.0) items as minimum standards. Item scores and
      qualitative comments were analyzed, followed by expert group discussion. RESULTS:
      One hundred and one people voted in round 1; 87 in round 2. Forty-seven items
      were reduced to 44 items across 3 new categories: 1) qualifying criteria, which
      are required in order for an intervention to be considered a decision aid (6
      items); 2) certification criteria, without which a decision aid is judged to have
      a high risk of harmful bias (10 items); and 3) quality criteria, believed to
      strengthen a decision aid but whose omission does not present a high risk of
      harmful bias (28 items). CONCLUSIONS: This study provides preliminary
      certification criteria for PDAs. Scoring and rating processes need to be tested
      and finalized. However, the process of appraising the quality of the clinical
      evidence reported by the PDA should be used to complement these criteria; the
      proposed standards are designed to rate the quality of the development process
      and shared decision-making design elements, not the quality of the PDA's clinical
      content.

PMID- 23963502
TI  - Sensitive detection of protein and miRNA cancer biomarkers using silicon-based
      photonic crystals and a resonance coupling laser scanning platform.
AB  - Enhancement of the fluorescent output of surface-based fluorescence assays by
      performing them upon nanostructured photonic crystal (PC) surfaces has been
      demonstrated to increase signal intensities by >8000*. Using the multiplicative
      effects of optical resonant coupling to the PC in increasing the electric field
      intensity experienced by fluorescent labels ("enhanced excitation") and the
      spatially biased funneling of fluorophore emissions through coupling to PC
      resonances ("enhanced extraction"), PC enhanced fluorescence (PCEF) can be
      adapted to reduce the limits of detection of disease biomarker assays, and to
      reduce the size and cost of high sensitivity detection instrumentation. In this
      work, we demonstrate the first silicon-based PCEF detection platform for
      multiplexed biomarker assay. The sensor in this platform is a silicon-based PC
      structure, comprised of a SiO2 grating that is overcoated with a thin film of
      high refractive index TiO2 and is produced in a semiconductor foundry for low
      cost, uniform, and reproducible manufacturing. The compact detection instrument
      that completes this platform was designed to efficiently couple fluorescence
      excitation from a semiconductor laser to the resonant optical modes of the PC,
      resulting in elevated electric field strength that is highly concentrated within
      the region <100 nm from the PC surface. This instrument utilizes a cylindrically
      focused line to scan a microarray in <1 min. To demonstrate the capabilities of
      this sensor-detector platform, microspot fluorescent sandwich immunoassays using
      secondary antibodies labeled with Cy5 for two cancer biomarkers (TNF-alpha and IL
      3) were performed. Biomarkers were detected at concentrations as low as 0.1 pM.
      In a fluorescent microarray for detection of a breast cancer miRNA biomarker miR
      21, the miRNA was detectable at a concentration of 0.6 pM. 

PMID- 23963503
TI  - Clinical and oncological effects of triplet chemotherapy followed by radical
      esophagectomy for resectable esophageal cancer associated with unfavorable
      prognostic factors.
AB  - PURPOSES: The purpose of this study was to evaluate the hypothesis that the
      survival of patients undergoing R0 resection after triplet chemotherapy for
      resectable esophageal cancer with unfavorable prognostic factors (Category 3)
      would be similar to that of patients undergoing esophagectomy for esophageal
      cancer without such factors (Category 1). METHODS: Patients with Category 3
      tumors were assigned to receive triplet chemotherapy consisting of 5
      fluorouracil, doxorubicin and nedaplatin (FAN) followed by radical esophagectomy.
      The outcomes of the bimodality treatment for Category 3 patients (n = 25) were
      compared with those of Category 1 patients (n = 41) in a prospective cohort
      study. RESULTS: Grade 3 or higher toxicity developed during chemotherapy in 32 %
      of the Category 3 patients, with no treatment-related deaths. No significant
      difference was detected in the surgery-related mortality and morbidity rates
      between the two groups. The recurrence-free survival was significantly worse in
      Category 3 than in Category 1 patients (p = 0.002), although the overall survival
      was not significantly different (p = 0.085) between the two groups in cases of R0
      resection (5-year survival rates: 34.4 vs. 66.5 %). CONCLUSIONS: Although FAN
      chemotherapy followed by radical esophagectomy can be safely performed, this
      treatment modality may not have sufficient power to cure Category 3 disease.

PMID- 23963504
TI  - In celebration of the 60th birthday of Professor Andrew D. Hamilton FRS.
AB  - An on-line collection of articles celebrating the 60th birthday of Professor
      Andrew D. Hamilton FRS has been published featuring contributions from students
      and colleagues past and present. This article hopes to provide an insight into
      the rise of a star in molecular recognition, ground breaking discoveries, and on
      a more light-hearted note, some fond reminiscences of research in Cambridge,
      Princeton, Pittsburgh, Yale and Oxford. 

PMID- 23963505
TI  - Double shelled hollow nanospheres with dual noble metal nanoparticle
      encapsulation for enhanced catalytic application.
AB  - We report the design and realization of double shelled @CeO2/M@M/TiO2 (M = Au
      and/or Pd) nanospheres with dual noble metal nanoparticles encapsulated in metal
      oxide shells via a layer-by-layer deposition process followed by an alkali
      etching method. The resulting nanospheres possess uniform sizes, variable shell
      components and thicknesses, adjustable noble metal nanoparticles encapsulated,
      regulable chamber spaces between the two shells, and good structural stability,
      which can be used as unique microreactors with extremely high catalytic activity
      and stability in the Suzuki-Miyaura coupling reaction, benzyl aerobic alcohol
      oxidation, and 4-nitrophenol reduction reaction due to their structural features
      with multiple interactions and strong synergistic effects between the noble metal
      nanoparticles and metal oxide shells, and less depletion of catalytic active
      species. The designed double shelled hollow @CeO2/M@M/TiO2 nanocatalysts can be
      used as novel catalyst systems with highly efficient catalytic performance for
      various catalytic reactions depending on their shell components and noble metal
      nanoparticles encapsulated. The synthetic strategy provides a new methodology to
      design high-performance and multifunctional nanocatalysts. 

PMID- 23963506
TI  - Meta-analysis of prevalence.
AB  - Meta-analysis is a method to obtain a weighted average of results from various
      studies. In addition to pooling effect sizes, meta-analysis can also be used to
      estimate disease frequencies, such as incidence and prevalence. In this article
      we present methods for the meta-analysis of prevalence. We discuss the logit and
      double arcsine transformations to stabilise the variance. We note the special
      situation of multiple category prevalence, and propose solutions to the problems
      that arise. We describe the implementation of these methods in the MetaXL
      software, and present a simulation study and the example of multiple sclerosis
      from the Global Burden of Disease 2010 project. We conclude that the double
      arcsine transformation is preferred over the logit, and that the MetaXL
      implementation of multiple category prevalence is an improvement in the
      methodology of the meta-analysis of prevalence. 

PMID- 23963508
TI  - Prescription n-3 fatty acids, but not eicosapentaenoic acid alone, improve
      reference memory-related learning ability by increasing brain-derived
      neurotrophic factor levels in SHR.Cg-Lepr(cp)/NDmcr rats, a metabolic syndrome
      model.
AB  - Metabolic syndrome is implicated in the decline of cognitive ability. We
      investigated whether the prescription n-3 fatty acid administration improves
      cognitive learning ability in SHR.Cg-Lepr(cp)/NDmcr (SHR-cp) rats, a metabolic
      syndrome model, in comparison with administration of eicosapentaenoic acid (EPA,
      C20:5, n-3) alone. Administration of TAK-085 [highly purified and concentrated n
      3 fatty acid formulation containing EPA ethyl ester and docosahexaenoic acid
      (DHA, C22:6, n-3) ethyl ester] at 300 mg/kg body weight per day for 13 weeks
      reduced the number of reference memory-related errors in SHR-cp rats, but EPA
      alone had no effect, suggesting that long-term TAK-085 administration improves
      cognitive learning ability in a rat model of metabolic syndrome. However, the
      working memory-related errors were not affected in either of the rat groups. TAK
      085 and EPA administration increased plasma EPA and DHA levels of SHR-cp rats,
      associating with an increase in EPA and DHA in the cerebral cortex. The TAK-085
      administration decreased the lipid peroxide levels and reactive oxygen species in
      the cerebral cortex and hippocampus of SHR-cp rats, suggesting that TAK-085
      increases antioxidative defenses. Its administration also increased the brain
      derived neurotrophic factor levels in the cortical and hippocampal tissues of TAK
      085-administered rats. The present study suggests that long-term TAK-085
      administration is a possible therapeutic strategy for protecting against
      metabolic syndrome-induced learning decline.

PMID- 23963509
TI  - Differential proteomic analysis of acute contusive spinal cord injury in rats
      using iTRAQ reagent labeling and LC-MS/MS.
AB  - In this experimental study, differential labeling with isobaric tags for relative
      and absolute quantitation (iTRAQ) reagents followed by liquid chromatography (LC)
      and tandem mass spectrometry (MS/MS) proteomic approach was used to investigate
      differences in the proteome of rat spinal cord at 24 h following a moderate
      contusion injury. Spinal cord protein samples from the injury epicenter (or from
      sham controls) were trypsinized and differentially labeled with iTRAQ isotopic
      reagents. The differentially labeled samples were then combined into one sample
      mixture, separated by LC, and analyzed using MS/MS. Proteins were quantified by
      comparing the peak areas of iTRAQ reporter fragment ions in MS/MS spectra. The
      outcome of this analysis revealed that proteins involved in ubiquitination,
      endocytosis and exocytosis, energy metabolism, inflammatory response, oxidative
      stress, cytoskeletal disruption, and vascular damage were significantly altered
      at 24 h following spinal cord injury (SCI). This study demonstrates the utility
      of the iTRAQ method in proteomic studies and provides further insights into
      secondary events that occur during acute times following SCI.

PMID- 23963511
TI  - Assessment of binding energies of atmospherically relevant clusters.
AB  - This work assesses the binding energies of atmospherically relevant clusters
      containing H2SO4, H2O, NH3 and (CH3)2NH using density functional theory. The
      performance of seven DFT functionals (B3LYP, CAM-B3LYP, M06-2X, PW91, LC-PW91,
      PBE0 and omegaB97X-D) is evaluated against high level explicitly correlated
      coupled cluster methods using a test set of 107 atmospherically relevant
      clusters. Our studies show that all the tested functionals correlate well with
      the coupled cluster results, but with highly varying mean absolute errors. The
      PBE0, CAM-B3LYP, PW91 and M06-2X functionals are found to perform similarly with
      errors in the range of 2.53-3.46 kcal mol(-1), while the B3LYP and LC-PW91
      functionals yield higher errors of 6.95 kcal mol(-1) and 10.66 kcal mol(-1),
      respectively. The omegaB97X-D functional gives the best estimate of the binding
      energies with a mean absolute error as low as 2.12 kcal mol(-1) over the large
      test set of clusters. 

PMID- 23963510
TI  - A novel genotoxicity assay of carbon nanotubes using functional macrophage
      receptor with collagenous structure (MARCO)-expressing chicken B lymphocytes.
AB  - Although carbon nanotubes (CNTs) are promising nanomaterials, their potential
      carcinogenicity is a major concern. We previously established a genetic method of
      analyzing genotoxicity of chemical compounds, where we evaluated their cytotoxic
      effect on the DT40 lymphoid cell line comparing DNA-repair-deficient isogenic
      clones with parental wild-type cells. However, application of our DT40 system for
      the cytotoxic and genotoxic evaluation of nanomaterials seemed to be difficult,
      because DT40 cells only poorly internalized nanoparticles. To solve this problem,
      we have constructed a chimeric gene encoding a trans-membrane receptor consisting
      of the 5' region of the transferrin receptor (TR) gene (to facilitate
      internalization of nanoparticles) and the 3' region of the macrophage receptor
      with collagenous structure (MARCO) gene (which is a receptor for environmental
      particles). We expressed the resulting MARCO-TR chimeric receptor on DNA-repair
      proficient wild-type cells and mutants deficient in base excision repair (FEN1 (
      /-)) and translesion DNA synthesis (REV3 (-/-)). We demonstrated that the chimera
      mediates uptake of particles such as fluorescence-tagged polystyrene particles
      and multi-walled carbon nanotubes (MWCNTs), with very poor uptake of those
      particles by DT40 cells not expressing the chimera. MWCNTs were cytotoxic and
      this effect was greater in FEN1 (-/-)and REV3 (-/-) cells than in wild-type
      cells. Furthermore, MWCNTs induced greater oxidative damage (measured as 8-OH-dG
      formation) and a larger number of mitotic chromosomal aberrations in repair
      deficient cells compared to repair-proficient cells. Taken together, our novel
      assay system using the chimeric receptor-expressing DT40 cells provides a
      sensitive method to screen for genotoxicity of CNTs and possibly other
      nanomaterials. 

PMID- 23963512
TI  - Application of alternative spatiotemporal metrics of ambient air pollution
      exposure in a time-series epidemiological study in Atlanta.
AB  - Exposure error in studies of ambient air pollution and health that use city-wide
      measures of exposure may be substantial for pollutants that exhibit
      spatiotemporal variability. Alternative spatiotemporal metrics of exposure for
      traffic-related and regional pollutants were applied in a time-series study of
      ambient air pollution and cardiorespiratory emergency department visits in
      Atlanta, GA, USA. Exposure metrics included daily central site monitoring for
      particles and gases; daily spatially refined ambient concentrations obtained from
      regional background monitors, local-scale dispersion, and hybrid air quality
      models; and spatially refined ambient exposures from population exposure models.
      Health risk estimates from Poisson models using the different exposure metrics
      were compared. We observed stronger associations, particularly for traffic
      related pollutants, when using spatially refined ambient concentrations compared
      with a conventional central site exposure assignment approach. For some
      relationships, estimates of spatially refined ambient population exposures showed
      slightly stronger associations than corresponding spatially refined ambient
      concentrations. Using spatially refined pollutant metrics, we identified
      socioeconomic disparities in concentration-response functions that were not
      observed when using central site data. In some cases, spatially refined pollutant
      metrics identified associations with health that were not observed using
      measurements from the central site. Complexity and challenges in incorporating
      modeled pollutant estimates in time-series studies are discussed. 

PMID- 23963513
TI  - How are the non-classically secreted bacterial proteins released into the
      extracellular milieu?
AB  - Most bacterial proteins that are destined to leave the cytoplasm are exported
      across the cell membrane to their sites of function. These proteins are generally
      exported via the classical secretion pathway, in which the signal peptide plays a
      central role. However, some bacterial proteins have been found in the
      extracellular milieu without any apparent signal peptide. As none of the
      classical secretion systems is involved in their secretion, this occurrence is
      termed non-classical protein secretion. The mechanism or mechanisms responsible
      for non-classical secretion are contentious. This review compiles evidence from
      the debate over whether the release of the non-classically secreted proteins is
      the result of cell lysis and discusses how these proteins are exported to the
      exterior of the cell. 

PMID- 23963514
TI  - Reductive amination of tertiary anilines and aldehydes.
AB  - An unprecedented oxidant-mediated reductive amination of tertiary anilines and
      aldehydes without external reducing agents was developed via the nucleophilic
      attack of the oxygen atom of the carbonyl group to in situ generated iminium
      ions, in which tertiary anilines were used as both nitrogen source and reducing
      agent for the first time. 

PMID- 23963515
TI  - Technologies for label-free separation of circulating tumor cells: from
      historical foundations to recent developments.
AB  - Circulating tumor cells (CTCs) are malignant cells shed into the bloodstream from
      a tumor that have the potential to establish metastases in different anatomical
      sites. The separation and subsequent characterization of these cells is emerging
      as an important tool for both biomarker discovery and the elucidation of
      mechanisms of metastasis. Established methods for separating CTCs rely on
      biochemical markers of epithelial cells that are known to be unreliable because
      of epithelial-to-mesenchymal transition, which reduces expression for epithelial
      markers. Emerging label-free separation methods based on the biophysical and
      biomechanical properties of CTCs have the potential to address this key
      shortcoming and present greater flexibility in the subsequent characterization of
      these cells. In this review we first present what is known about the biophysical
      and biomechanical properties of CTCs from historical studies and recent research.
      We then review biophysical label-free technologies that have been developed for
      CTC separation, including techniques based on filtration, hydrodynamic
      chromatography, and dielectrophoresis. Finally, we evaluate these separation
      methods and discuss requirements for subsequent characterization of CTCs. 

PMID- 23963516
TI  - Genetic and neurophysiological correlates of the age of onset of alcohol use
      disorders in adolescents and young adults.
AB  - Discrete time survival analysis was used to assess the age-specific association
      of event-related oscillations (EROs) and CHRM2 gene variants on the onset of
      regular alcohol use and alcohol dependence. The subjects were 2,938 adolescents
      and young adults ages 12-25. Results showed that the CHRM2 gene variants and ERO
      risk factors had hazards which varied considerably with age. The bulk of the
      significant age-specific associations occurred in those whose age of onset was
      under 16. These associations were concentrated in those subjects who at some time
      took an illicit drug. These results are consistent with studies which associate
      greater rates of alcohol dependence among those who begin drinking at an early
      age. The age specificity of the genetic and neurophysiological factors is
      consistent with recent studies of adolescent brain development, which locate an
      interval of heightened vulnerability to substance use disorders in the early to
      mid teens.

PMID- 23963518
TI  - Differential immune response of mallard duck peripheral blood mononuclear cells
      to two highly pathogenic avian influenza H5N1 viruses with distinct pathogenicity
      in mallard ducks.
AB  - CK10 and GS10 are two H5N1 highly pathogenic influenza viruses of similar genetic
      background but differ in their pathogenicity in mallard ducks. CK10 is highly
      pathogenic whereas GS10 is low pathogenic. In this study, strong inflammatory
      response in terms of the expression level of several cytokines was observed in
      mallard duck peripheral blood mononuclear cells (PBMC) infected with CK10 while
      mild response was triggered in those by GS10 infection. Two remarkable and
      intense peaks of immune response were induced by CK10 infection within 24 hours
      (at 8 and 24 hours post infection, respectively) without reducing the virus
      replication. Our observations indicated that sustained and intense innate immune
      responses may be central to the high pathogenicity caused by CK10 in ducks.

PMID- 23963517
TI  - Origin of the chemical and kinetic stability of graphene oxide.
AB  - At moderate temperatures (<= 70 degrees C), thermal reduction of graphene oxide
      is inefficient and after its synthesis the material enters in a metastable state.
      Here, first-principles and statistical calculations are used to investigate both
      the low-temperature processes leading to decomposition of graphene oxide and the
      role of ageing on the structure and stability of this material. Our study shows
      that the key factor underlying the stability of graphene oxide is the tendency of
      the oxygen functionalities to agglomerate and form highly oxidized domains
      surrounded by areas of pristine graphene. Within the agglomerates of functional
      groups, the primary decomposition reactions are hindered by both geometrical and
      energetic factors. The number of reacting sites is reduced by the occurrence of
      local order in the oxidized domains, and due to the close packing of the oxygen
      functionalities, the decomposition reactions become - on average - endothermic by
      more than 0.6 eV.

PMID- 23963520
TI  - Exposure science: a need to focus on conducting scientific studies, rather than
      debating its concepts.

PMID- 23963523
TI  - Energy expenditure during barbiturate coma.
AB  - BACKGROUND: Barbiturate coma may have a significant effect on metabolic rate, but
      the phenomenon is not extensively studied. The primary purpose of the current
      study was to compare the metabolic rate of general critical care patients with
      those requiring barbiturate coma. A secondary purpose was to evaluate the
      accuracy of the Penn State prediction equation between these 2 groups of
      patients. MATERIALS AND METHODS: Indirect calorimetry was used to measure the
      resting metabolic rate of mechanically ventilated, critically ill patients in a
      barbiturate coma and those of similar height, weight, and age but not in a
      barbiturate coma. Measurements of resting metabolic rate were compared with
      predictions using the Penn State equation accounting for body size, body
      temperature, and minute ventilation. RESULTS: The barbiturate coma group had a
      lower resting metabolic rate than the control group that remained lower even
      after adjustment for predicted healthy metabolic rate and maximum body
      temperature (1859 +/- 290 vs 2037 +/- 289 kcal/d, P = .020). When minute
      ventilation was also included in the analysis, the resting metabolic rate between
      the groups became statistically insignificant (1929 +/- 229 vs 2023 +/- 226
      kcal/d, P = .142). The Penn State equation, which uses these variables, was
      accurate in 73% of the control patients and also the barbiturate coma patients.
      CONCLUSION: Resting metabolic rate is moderately reduced in barbiturate coma, but
      the decrease is out of proportion with changes in body temperature. However, if
      both body temperature and minute ventilation are considered, then the change is
      predictable.

PMID- 23963522
TI  - BRAF mutation in sporadic colorectal cancer and Lynch syndrome.
AB  - The aim of the study was to detect mutations of BRAF oncogene in colorectal
      cancer and to use this information to identify Lynch syndrome patients.
      Consecutive cases of primary colorectal cancer (n = 137) were analyzed for MLH1
      protein expression using immunohistochemistry (IHC). BRAF V600E mutation was
      detected by IHC using a specific monoclonal antibody (VE1) and by qPCR. All MLH1
      protein-negative cases were subjected to microsatellite instability analysis and
      MLH1 promoter methylation assay. MLH1 protein expression deficiency and high
      microsatellite instability (MSI-H) were detected in 18 of the 137 (13.1%)
      consecutive colorectal cancer specimens. Detection of the BRAF V600E mutation by
      IHC was 100% sensitive and specific as compared to qPCR, and this mutation was
      frequently present in the MSI-H group (77.8%; 14/18) and less frequently in the
      microsatellite-stable group (7.6%; 9/118). All BRAF V600E mutated cases of the
      MSI-H group presented with a MLH1 promoter methylation (14/14) as detected by
      methylation-specific multiplex ligation-dependent probe amplification. When BRAF
      was wild type in the MSI-H group, only one MLH1 promoter methylation was detected
      (1/4), and of the remaining three cases without MLH1 methylation, two were
      identified to harbor an MLH1 mutation consistent with Lynch syndrome. Finally, 11
      previously confirmed Lynch syndrome cases were analyzed for BRAF V600E mutation,
      and all of them were wild type. In conclusion, detection of BRAF V600E in
      colorectal cancer specimens by IHC is sensitive and specific and may help to
      identify Lynch syndrome patients.

PMID- 23963524
TI  - Structures, mobilities, electronic and magnetic properties of point defects in
      silicene.
AB  - In the fabrication and processing of silicene monolayers, structural defects are
      almost inevitable. Using ab initio calculations, we systemically investigated the
      structures, formation energies, migration behaviors and electronic/magnetic
      properties of typical point defects in silicene, including the Stone-Wales (SW)
      defect, single and double vacancies (SVs and DVs), and adatoms. We found that SW
      can be effectively recovered by thermal annealing. SVs have much higher mobility
      than DVs and two SVs are very likely to coalesce into one DV to lower the energy.
      Existence of SW and DVs may induce small gaps in silicene, while the SV defect
      may transform semimetallic silicene into metallic. Adatoms are unexpectedly
      stable and can affect the electronic properties of silicene dramatically.
      Especially, Si adatoms as self-dopants in silicene sheets can induce long-range
      spin polarization as well as a remarkable band gap, thus achieving an all-silicon
      magnetic semiconductor. The present theoretical results provide valuable insights
      into identification of these defects in experiments and understanding their
      effects on the physical properties of silicene. 

PMID- 23963525
TI  - Facile preparation of a novel high performance benzoxazine-CNT based nano-hybrid
      network exhibiting outstanding thermo-mechanical properties.
AB  - Untreated multi-walled carbon nanotubes (MWCNTs) have been dispersed in two
      benzoxazine precursors following an easy procedure. The strong intrinsic
      interactions of CNTs with a selected precursor give rise to the formation of a
      reinforced network with outstanding thermo-mechanical properties. 

PMID- 23963526
TI  - Analogy among microfluidics, micromechanics, and microelectronics.
AB  - We wish to illuminate the analogous link between microfluidic-based devices, and
      the already established pairing of micromechanics and microelectronics to create
      a triangular/three-way scientific relationship as a means of interlinking
      familial disciplines and accomplishing two primary goals: (1) to facilitate the
      modeling of multidisciplinary domains; and, (2) to enable us to co-simulate the
      entire system within a compact circuit simulator (e.g., Cadence or SPICE). A
      microfluidic channel-like structure embedded in a micro-electro-mechanical
      resonator via our proposed CMOS-MEMS technology is used to illustrate the
      connections among microfluidics, micromechanics, and microelectronics. 

PMID- 23963527
TI  - Is aging a barrier to reprogramming? Lessons from induced pluripotent stem cells.
AB  - The discovery of induced pluripotent stem cells (iPSCs) has the potential to
      revolutionize the field of regenerative medicine. In the past few years, iPSCs
      have been the subject of intensive research towards their application in disease
      modeling and drug screening. In the future, these cells may be applied in cell
      therapy to replace or regenerate tissues by autologous transplantation. However,
      two major hurdles need to be resolved in order to reach the later goal: the low
      reprogramming efficiency and the safety risks, such as the integration of foreign
      DNA into the genome of the cells and the tumor formation potential arising from
      transplantation of residual undifferentiated cells. Recently, aging emerged as
      one of the barriers that accounts, at least in part, for the low reprogramming
      efficiency of bona fide iPSCs. Here, we review the molecular pathways linking
      aging and reprogramming along with the unanswered questions in the field. We
      discuss whether reprogramming rejuvenates the molecular and cellular features
      associated with age, and present the recent advances with iPSC-based models,
      contributing to our understanding of physiological and premature aging. 

PMID- 23963528
TI  - Supercritically exfoliated ultrathin vanadium pentoxide nanosheets with high rate
      capability for lithium batteries.
AB  - Ultrathin V2O5 nanosheets were successfully prepared through supercritical
      solvothermal reaction followed by annealing treatment. The formation of ultrathin
      nanosheets is owing to Ostwald ripening and the effect of supercritical fluids.
      As cathode material for lithium batteries, the ultrathin V2O5 nanosheets exhibit
      a capacity of 108 mA h g(-1) at a high rate of up to 10 C at 2.4-4 V and
      excellent cyclability with little capacity loss after 200 cycles. The enhanced
      rate performance is attributed to the shortened diffusion distance and the
      increased electrode-electrolyte contact area of the ultrathin nanosheet
      structure. It is also demonstrated that the supercritical solvothermal method is
      effective and facile to scalably synthesize ultrathin nanomaterials for lithium
      batteries. 

PMID- 23963529
TI  - Effects of amphetamine and methylphenidate on delay discounting in rats:
      interactions with order of delay presentation.
AB  - RATIONALE: Drug effects on delay discounting are thought to reflect changes in
      sensitivity to reinforcer delay, although other behavioral mechanisms might be
      involved. One strategy for revealing the influence of different behavioral
      mechanisms is to alter features of the procedures in which they are studied.
      OBJECTIVE: This experiment examined whether the order of delay presentation under
      within-session delay discounting procedures impacts drug effects on discounting.
      METHODS: Rats responded under a discrete-trial choice procedure in which
      responses on one lever delivered one food pellet immediately and responses on the
      other lever delivered three food pellets either immediately or after a delay. The
      delay to the larger reinforcer (0, 4, 8, 16, and 32 s) was varied within session
      and the order of delay presentation (ascending or descending) varied between
      groups. RESULTS: Amphetamine (0.1-1.78 mg/kg) and methylphenidate (1.0-17.8
      mg/kg) shifted delay functions upward in the ascending group (increasing choice
      of the larger reinforcer) and downward in the descending group (decreasing choice
      of the larger reinforcer). Morphine (1.0-10.0 mg/kg) and delta-9
      tetrahydrocannabinol (0.32-5.6 mg/kg) tended to shift the delay functions
      downward, regardless of order of delay presentation, thereby reducing choice of
      the larger reinforcer, even when both reinforcers were delivered immediately.
      CONCLUSION: The effects of amphetamine and methylphenidate under delay
      discounting procedures differed depending on the order of delay presentation,
      indicating that drug-induced changes in discounting were due, in part, to
      mechanisms other than altered sensitivity to reinforcer delay. Instead,
      amphetamine and methylphenidate altered responding in a manner consistent with
      increased behavioral perseveration.

PMID- 23963532
TI  - Application of the CRISPR-Cas system for efficient genome engineering in plants.

PMID- 23963531
TI  - Socio-demographic and clinical characteristics of heavy and non-heavy smokers
      among schizophrenia inpatients in a Chinese Han population.
AB  - OBJECTIVE: Despite higher smoking rates in schizophrenia, few studies have
      explored the clinical-demographic correlates of different amounts of smoking
      exposure. Little is known about the association between smoking severity and
      clinical phenotypes in Chinese patients with schizophrenia. MATERIALS AND
      METHODS: We investigated differences between heavy (>=1 pack/day) and non-heavy
      (<1 pack/day) smoking in 550 male inpatients with schizophrenia using clinician
      administered questionnaires and the Fagerstrom Test for Nicotine Dependence. They
      also were rated on the Positive and Negative Symptom Scale (PANSS), the Simpson
      and Angus Extrapyramidal Symptom Rating Scale (SAES), and the Abnormal
      Involuntary Movement Scale (AIMS), as well as were assayed with laboratory tests
      and an electrocardiogram. RESULTS: Heavy smoking prevalence was approximately 31
      %. Compared to the non-heavy smokers, the heavy smokers were younger, more with
      paranoid subtype but less with disorganized subtype schizophrenia, smoked at an
      earlier age, fewer getting clozapine or all atypical antipsychotics together, and
      were taking larger doses of antipsychotic drugs. The heavy smokers scored
      significantly lower on the PANSS negative symptom subscore and total score, and
      also on the SAES and AIMS scores than the non-heavy smokers. In addition, heavy
      smokers displayed longer rate-corrected electrocardiographic QT intervals, but
      without any significant differences in other laboratory tests. CONCLUSION: Our
      results suggest several clinical or demographic differences between the heavy and
      non-heavy smoking patients with schizophrenia in a Chinese population. Heavy
      smoking remains a general health risk for schizophrenia.

PMID- 23963530
TI  - A multistep general theory of transition to addiction.
AB  - BACKGROUND: Several theories propose alternative explanations for drug addiction.
      OBJECTIVES: We propose a general theory of transition to addiction that
      synthesizes knowledge generated in the field of addiction into a unitary
      explanatory frame. MAJOR PRINCIPLES OF THE THEORY: Transition to addiction
      results from a sequential three-step interaction between: (1) individual
      vulnerability; (2) degree/amount of drug exposure. The first step, sporadic
      recreational drug use is a learning process mediated by overactivation of
      neurobiological substrates of natural rewards that allows most individuals to
      perceive drugs as highly rewarding stimuli. The second, intensified, sustained,
      escalated drug use occurs in some vulnerable individuals who have a hyperactive
      dopaminergic system and impaired prefrontal cortex function. Sustained and
      prolonged drug use induces incentive sensitization and an allostatic state that
      makes drugs strongly wanted and needed. Habit formation can also contribute to
      stabilizing sustained drug use. The last step, loss of control of drug intake and
      full addiction, is due to a second vulnerable phenotype. This loss-of-control
      prone phenotype is triggered by long-term drug exposure and characterized by long
      lasting loss of synaptic plasticity in reward areas in the brain that induce a
      form of behavioral crystallization resulting in loss of control of drug intake.
      Because of behavioral crystallization, drugs are now not only wanted and needed
      but also pathologically mourned when absent. CONCLUSIONS: This general theory
      demonstrates that drug addiction is a true psychiatric disease caused by a three
      step interaction between vulnerable individuals and amount/duration of drug
      exposure.

PMID- 23963533
TI  - [The importance of pathology in the German prostate cancer study PREFERE].
AB  - Prostate cancer is the most common carcinoma of elderly males and holds the third
      place in the ranking of cancer-specific mortality. However, total mortality rate
      of 3 % is low and half of the patients die from other diseases, which is for the
      most part due to significantly improved diagnostic methods and the increasing use
      of prostate-specific antigen (PSA) screening. This has led to a stage migration
      towards early tumor stages that are prognostically heterogeneous and require
      differentiated treatment. The German and European guidelines recommend four
      therapy options (i.e. radical prostatectomy, percutaneous irradiation, permanent
      seed implantation and active surveillance) for localized prostate cancer and from
      contemporary study data it is unclear which therapy is most beneficial. This will
      be the subject of the PREFERE trial, a prospective randomized multicentre trial
      which plans to recruit 7,600 patients and to observe them over a period of up to
      17 years. The histopathological diagnosis of the primary biopsy plays a crucial
      role in the inclusion criteria, as this article outlines in detail. 

PMID- 23963534
TI  - A role for endoplasmic reticulum exit sites in foot-and-mouth disease virus
      infection.
AB  - Picornaviruses replicate their genomes in association with cellular membranes.
      While enteroviruses are believed to utilize membranes of the early secretory
      pathway, the origin of the membranes used by foot-and-mouth disease virus (FMDV)
      for replication are unknown. Secretory-vesicle traffic through the early
      secretory pathway is mediated by the sequential acquisition of two distinct
      membrane coat complexes, COPII and COPI, and requires the coordinated actions of
      Sar1, Arf1 and Rab proteins. Sar1 is essential for generating COPII vesicles at
      endoplasmic reticulum (ER) exit sites (ERESs), while Arf1 and Rab1 are required
      for subsequent vesicle transport by COPI vesicles. In the present study, we have
      provided evidence that FMDV requires pre-Golgi membranes of the early secretory
      pathway for infection. Small interfering RNA depletion of Sar1 or expression of a
      dominant-negative (DN) mutant of Sar1a inhibited FMDV infection. In contrast, a
      dominant-active mutant of Sar1a, which allowed COPII vesicle formation but
      inhibited the secretory pathway by stabilizing COPII coats, caused major
      disruption to the ER-Golgi intermediate compartment (ERGIC) but did not inhibit
      infection. Treatment of cells with brefeldin A, or expression of DN mutants of
      Arf1 and Rab1a, disrupted the Golgi and enhanced FMDV infection. These results
      show that reagents that block the early secretory pathway at ERESs have an
      inhibitory effect on FMDV infection, while reagents that block the early
      secretory pathway immediately after ER exit but before the ERGIC and Golgi make
      infection more favourable. Together, these observations argue for a role for Sar1
      in FMDV infection and that initial virus replication takes place on membranes
      that are formed at ERESs. 

PMID- 23963536
TI  - Metabolomic analysis of amino acid metabolism in colitic rats supplemented with
      lactosucrose.
AB  - Intestinal inflammation causes metabolic disorders. The purpose of this study was
      to determine the effect of dietary supplementation with lactosucrose (LS) on the
      serum metabolome and intestinal luminal content of fatty acids in colitic rats.
      Colitis was induced in rats using trinitrobenzene sulfonic acid. Subsequently,
      rats received intragastric administration of either 250 mg LS/kg body weight or
      saline (the control group) every day for 5 weeks. Short-chain fatty acids in the
      intestinal lumen, blood profile, and metabolites in serum were measured,
      respectively, using gas chromatography, biochemistry analyzer, and nuclear
      magnetic resonance-based metabolomics combined with multivariate statistics.
      Metabolic effects of LS included: (1) decreases in concentrations of branched
      chain amino acids (isoleucine and valine), alanine, citric acid, trimethylamine
      oxide and taurine, and the abundance of aspartate aminotransferase in serum; (2)
      increases in concentrations of glucose metabolites (including succinate) in
      serum; and (3) altered concentrations of butyrate in the cecal content and of
      butyrate and acetate in the colon content. The results indicate that LS
      supplementation to colitic rats affects whole-body metabolism of amino acids and
      release of aspartate aminotransferase and alkaline phosphatase from tissues into
      the blood circulation, and enhances the production of short-chain fatty acids in
      the intestinal lumen. 

PMID- 23963537
TI  - Neuroprotective role of taurine during aging.
AB  - Aging of the brain is characterized by several neurochemical modifications
      involving structural proteins, neurotransmitters, neuropeptides and related
      receptors. Alterations of neurochemical indices of synaptic function are
      indicators of age-related impairment of central functions, such as locomotion,
      memory and sensory performances. Several studies demonstrate that ionotropic GABA
      receptors, glutamate decarboxylase (GAD), and somatostatinergic subpopulations of
      GABAergic neurons are markedly decreased in experimental animal brains during
      aging. Additionally, levels of several neuropeptides co-expressed with GAD
      decrease during aging. Thus, the age-related decline in cognitive functions could
      be attributable, at least in part, to decrements in GABA inhibitory
      neurotransmission. In this study, we showed that chronic supplementation of
      taurine to aged mice significantly ameliorated the age-dependent decline in
      spatial memory acquisition and retention. We also demonstrated that concomitant
      with the amelioration in cognitive function, taurine caused significant
      alterations in the GABAergic and somatostatinergic system. These changes included
      (1) increased levels of the neurotransmitters GABA and glutamate, (2) increased
      expression of both isoforms of GAD (65 and 67) and the neuropeptide somatostatin,
      (3) decreased hippocampal expression of the beta3 subunits of the GABAA receptor,
      (4) increased expression in the number of somatostatin-positive neurons, (5)
      increased amplitude and duration of population spikes recorded from CA1 in
      response to Schaefer collateral stimulation and (6) enhanced paired pulse
      facilitation in the hippocampus. These specific alterations of the inhibitory
      system caused by taurine treatment oppose those naturally occurring in the aging
      brain, suggesting a protective role of taurine in this process. An increased
      understanding of age-related neurochemical changes in the GABAergic system will
      be important in elucidating the underpinnings of the functional changes of aging.
      Taurine supplementation might help forestall the age-related decline in cognitive
      functions through interaction with the GABAergic system. 

PMID- 23963538
TI  - Activation of polyamine catabolic enzymes involved in diverse responses against
      epibrassinolide-induced apoptosis in LNCaP and DU145 prostate cancer cell lines.
AB  - Epibrassinolide (EBR) is a biologically active compound of the brassinosteroids,
      steroid-derived plant growth regulator family. Generally, brassinosteroids are
      known for their cell expansion and cell division-promoting roles. Recently, EBR
      was shown as a potential apoptotic inducer in various cancer cells without
      affecting the non-tumor cell growth. Androgen signaling controls cell
      proliferation through the interaction with the androgen receptor (AR) in the
      prostate gland. Initially, the development of prostate cancer is driven by
      androgens. However, in later stages, a progress to the androgen-independent stage
      is observed, resulting in metastatic prostate cancer. The androgen-responsive or 
      irresponsive cells are responsible for tumor heterogeneity, which is an obstacle
      to effective anti-cancer therapy. Polyamines are amine-derived organic compounds,
      known for their role in abnormal cell proliferation as well as during malignant
      transformation. Polyamine catabolism-targeting agents are being investigated
      against human cancers. Many chemotherapeutic agents including polyamine analogs
      have been demonstrated to induce polyamine catabolism that depletes polyamine
      levels and causes apoptosis in tumor models. In our study, we aimed to
      investigate the mechanism of apoptotic cell death induced by EBR, related with
      polyamine biosynthetic and catabolic pathways in LNCaP (AR+), DU145 (AR-)
      prostate cancer cell lines and PNT1a normal prostate epithelial cell line.
      Induction of apoptotic cell death was observed in prostate cancer cell lines
      after EBR treatment. In addition, EBR induced the decrease of intracellular
      polyamine levels, accompanied by a significant ornithine decarboxylase (ODC) down
      regulation in each prostate cancer cell and also modulated ODC antizyme and
      antizyme inhibitor expression levels only in LNCaP cells. Catabolic enzymes SSAT
      and PAO expression levels were up-regulated in both cell lines; however, the
      specific SSAT and PAO siRNA treatments prevented the EBR-induced apoptosis only
      in LNCaP (AR+) cells. In a similar way, MDL 72,527, the specific PAO and SMO
      inhibitor, co-treatment with EBR during 24 h, reduced the formation of cleaved
      fragments of PARP in LNCaP (AR+) cells.

PMID- 23963539
TI  - A case of renal gamma2 heavy-chain deposition disease accompanied by rapid
      progressive renal failure.
AB  - BACKGROUND: The recently described heavy-chain deposition disease (HCDD) is a
      comparatively rare monoclonal immunoglobulin disorder characterized
      histopathologically by glomerular and tubular basement membrane deposition of
      nonamyloidotic monoclonal heavy chains without associated light chains. METHOD:
      We have described a case of gamma2-HCDD presenting with proteinuria,
      microhematuria, severe hypertension, and rapidly progressive renal failure, which
      serum creatinine level was only 1.52 mg/dL in early stage HCDD, and the
      clinicopathologic features of this case have been compared with other reported
      cases of gamma2-HCDD. RESULTS: Renal biopsy disclosed nodular sclerosing
      glomerulopathy. Immunofluorescence analysis revealed IgG2 (2+) heavy chain and C3
      (+) in the mesangium and along the capillary walls and tubular basement membranes
      without IgA, IgM, kappa and lambda light chains. Electron microscopy revealed
      electron-dense deposits along the glomerular and tubular basement membranes as
      well as in the mesangium. Moreover, regardless of therapy, the condition of the
      patient progressively deteriorated, with less than 3 months of renal survival.
      CONCLUSION: Rapid progressive renal failure was a common feature in both cases of
      gamma2-HCDD. We propose that a possible link exists between prognosis of renal
      HCDD and the subclass of heavy chain deposited in the kidney.

PMID- 23963541
TI  - Swallowing difficulties with oral drugs among polypharmacy patients attending
      community pharmacies.
AB  - BACKGROUND: Swallowing difficulties are common and can affect patients' ability
      to take solid oral dosage forms, thus compromising medication adherence.
      Strategies developed by patients to overcome such difficulties while taking
      medicines have seldom been described. OBJECTIVE: To determine prevalence and
      characteristics of swallowing difficulties among primary care patients attending
      their community pharmacies; to explore strategies developed by patients to
      overcome their difficulties, and health professionals' awareness of these
      problems. SETTING: Prospective study with a semi-structured questionnaire in
      random community pharmacies located in two Swiss regions. METHOD: In each
      pharmacy, an interviewer asked 16 questions to each consecutive patient (18 years
      and older) with a prescription for at least 3 different solid oral forms. MAIN
      OUTCOME MEASURE: Quantification of number of patients with swallowing
      difficulties and detailed description of difficulties. RESULTS: Among 122
      pharmacies, 59 (48 %) accepted to join the study and 410 patients were enrolled.
      Thirty-seven patients (9.0 %) reported ongoing swallowing difficulties, while 55
      patients (13.4 %) reported past difficulties. For the majority of patients,
      difficulties occurred at each single dose (83.7 %), with a single medication
      (59.8 %) and lasted for less than 12 months (53.8 %). Number of tablets was not
      the main trigger. Swallowing difficulties impaired extremely daily life in 12 %
      of the patients. Intentional non adherence (23 % of patients) and altering the
      oral dose formulation were the most common and potentially harmful strategies
      used by patients to overcome their swallowing difficulties. According to the
      patients, pharmacists and physicians rarely inquired about their swallowing
      difficulties. CONCLUSION: We report a fairly high prevalence of swallowing
      difficulties in polypharmacy patients attending their community pharmacies.
      Pharmacists have to interview patients on their swallowing difficulties in a more
      systematic way, support patients in finding solutions and refer them to their
      physician if necessary to ensure continuity in care.

PMID- 23963542
TI  - Pharmacists' attitudes and perceived barriers to provision of adherence support
      in Australia.
AB  - BACKGROUND: Adherence to therapy is a key to achieving good clinical outcomes.
      Promoting medication adherence requires a range of strategies that primarily
      focus on fostering behavioral change. Community pharmacists are well placed to
      deliver adherence support to patients. AIM: To investigate community pharmacists'
      activities in supporting patient medication adherence in their practice; and to
      assess pharmacists' attitudes and barriers to adherence support. METHOD: A sample
      of 500 pharmacies was randomly selected from a list of community pharmacies in
      the state of New South Wales (Australia) and mailed a questionnaire focusing on
      provision of adherence support, pharmacists' attitudes, and barriers to adherence
      support. Two follow-up reminders were sent to non-responding pharmacies after 2
      and 6 weeks. RESULT: A response rate of 27.6 % was achieved (n = 126), consistent
      with recent research studies. For less than half (42 %) of prescriptions
      dispensed, pharmacists reported providing strategies to identify non-adherent
      patients. Providing dose administration aids was the most common method to
      support adherence used by pharmacists (95 %). Most (98 %) agreed that it was
      their role to promote patients' adherence. However 64 and 52 % reported that
      patients' time pressures and poor health literacy, respectively, were the main
      barriers to provision of adherence support. Around 25 % of respondents reported
      that they had received training programs on providing medication adherence
      support. CONCLUSION: Community pharmacists employed a limited range of strategies
      to identify and address non-adherence to medications. Moreover, the provision of
      adherence support was episodic and infrequent. However, the majority of
      pharmacists believed that it is their role to promote patients adherence. Time
      pressures for both pharmacists and patients were perceived to be a major barrier.

PMID- 23963543
TI  - The diagnostic utility of separation anxiety disorder symptoms: an item response
      theory analysis.
AB  - At present, it is not clear whether the current definition of separation anxiety
      disorder (SAD) is the optimal classification of developmentally inappropriate,
      severe, and interfering separation anxiety in youth. Much remains to be learned
      about the relative contributions of individual SAD symptoms for informing
      diagnosis. Two-parameter logistic Item Response Theory analyses were conducted on
      the eight core SAD symptoms in an outpatient anxiety sample of treatment-seeking
      children (N = 359, 59.3 % female, M Age = 11.2) and their parents to determine
      the diagnostic utility of each of these symptoms. Analyses considered values of
      item threshold, which characterize the SAD severity level at which each symptom
      has a 50 % chance of being endorsed, and item discrimination, which characterize
      how well each symptom distinguishes individuals with higher and lower levels of
      SAD. Distress related to separation and fear of being alone without major
      attachment figures showed the strongest discrimination properties and the lowest
      thresholds for being endorsed. In contrast, worry about harm befalling attachment
      figures showed the poorest discrimination properties, and nightmares about
      separation showed the highest threshold for being endorsed. Distress related to
      separation demonstrated crossing differential item functioning associated with
      age-at lower separation anxiety levels excessive fear at separation was more
      likely to be endorsed for children >=9 years, whereas at higher levels this
      symptom was more likely to be endorsed by children <9 years. Implications are
      discussed for optimizing the taxonomy of SAD in youth. 

PMID- 23963544
TI  - The effects of instructions on mothers' ratings of attention
      deficit/hyperactivity disorder symptoms in referred children.
AB  - Tested whether instructions for how to rate child attention-deficit/hyperactivity
      disorder (ADHD) symptoms would improve the agreement between mothers' ratings of
      symptoms in their children and ratings provided by teachers and objective
      observers. Sixty-eight mothers of 5 to 12 year old children (53 boys and 15
      girls) referred for ADHD assessment were randomly assigned to receive or not
      receive the instructions. Mothers and teachers rated the children on the SNAP-IV
      Rating Scale and objective observers rated the children's behavior during
      structured tasks. Relations between mother and teacher, and mother and observer
      ratings were generally stronger for mothers in the Instruction group compared to
      mothers in the No Instruction group, in some cases significantly stronger. The
      instructional materials also improved mothers' knowledge of how to rate ADHD
      symptoms and reduced some associations between mothers' ratings and family
      socioeconomic status. These instructions have the potential to improve clinical
      assessments of child ADHD symptoms. 

PMID- 23963545
TI  - Plasmonic photocatalysis properties of Au nanoparticles precipitated
      anatase/rutile mixed TiO2 nanotubes.
AB  - Anatase/rutile mixed titania nanotubes (TiO2 NTs) precipitated with gold
      nanoparticles (Au NPs), i.e. Au/TiO2, have been synthesized and investigated on
      visible photocatalysis properties. A deposition-precipitation (DP) method was
      adopted to reduce the gold precursor to Au NPs within the preformed TiO2 NTs by
      the emulsion electrospinning technique. The optimal visible photocatalytic
      activity was found in the sample Au3(DP350)/TiO2 with a loading of 3 wt% Au NPs
      and calcining at 350  degrees C. Through transmission electron microscopy, Au NPs
      of 4.16 nm diameter were observed at the interface between the anatase and rutile
      phases in the optimal Au3(DP350)/TiO2 sample, and these joint active sites at the
      interface were beneficial for charge separation. The obtained optimal
      photocatalytic efficiency of Au3(DP350)/TiO2 was ascribed to the synergistic
      effect of the enhanced visible absorption and the anatase/rutile mixed-phase
      composition, and the possible mechanism for this was discussed in detail. 

PMID- 23963535
TI  - Longitudinal analysis of intra-host simian immunodeficiency virus recombination
      in varied tissues of the rhesus macaque model for neuroAIDS.
AB  - Human immunodeficiency virus intra-host recombination has never been studied in
      vivo both during early infection and throughout disease progression. The CD8
      depleted rhesus macaque model of neuroAIDS was used to investigate the impact of
      recombination from early infection up to the onset of neuropathology in animals
      inoculated with a simian immunodeficiency virus (SIV) swarm. Several lymphoid and
      non-lymphoid tissues were collected longitudinally at 21 days post-infection
      (p.i.), 61 days p.i. and necropsy (75-118 days p.i.) from four macaques that
      developed SIV-encephalitis or meningitis, as well as from two animals euthanized
      at 21 days p.i. The number of recombinant sequences and breakpoints in different
      tissues and over time from each primate were compared. Breakpoint locations were
      mapped onto predicted RNA and protein secondary structures. Recombinants were
      found at each time point and in each primate as early as 21 days p.i. No
      association was found between recombination rates and specific tissue of origin.
      Several identical breakpoints were identified in sequences derived from different
      tissues in the same primate and among different primates. Breakpoints
      predominantly mapped to unpaired nucleotides or pseudoknots in RNA secondary
      structures, and proximal to glycosylation sites and cysteine residues in protein
      sequences, suggesting selective advantage in the emergence of specific
      recombinant sequences. Results indicate that recombinant sequences can become
      fixed very early after infection with a heterogeneous viral swarm. Features of
      RNA and protein secondary structure appear to play a role in driving the
      production of recombinants and their selection in the rapid disease model of
      neuroAIDS.

PMID- 23963547
TI  - From haemochromatosis to liver transplant.

PMID- 23963548
TI  - Tourette's syndrome.

PMID- 23963549
TI  - Friends and family test results only moderately associated with conventional
      measures of hospital quality.

PMID- 23963546
TI  - Valsartan/amlodipine compared to nifedipine GITS in patients with hypertension
      inadequately controlled by monotherapy.
AB  - INTRODUCTION: Current hypertension guidelines recommend single-pill combinations
      because they not only improve convenience and compliance to therapy and thus
      blood pressure (BP) control, but also reduce health-care costs. This study
      compared the efficacy and safety of valsartan/amlodipine single-pill combination
      with nifedipine gastrointestinal therapeutic system (GITS) in Chinese patients
      with hypertension who were inadequately controlled with monotherapy. METHODS: In
      this multicenter, open-label, active-controlled, parallel-group study, 564
      patients with hypertension not adequately controlled by prior monotherapy were
      randomized to receive valsartan/amlodipine 80/5 mg or nifedipine GITS 30 mg once
      daily for 12 weeks. RESULTS: In the intention-to-treat analysis (n = 540),
      valsartan/amlodipine (n = 272) showed a least-square mean reduction of -16.6
      versus -10.8 mmHg by nifedipine GITS (n = 268; mean between-treatment difference:
      -5.8 mmHg; P < 0.0001) from baseline to week 12. The corresponding results for
      mean sitting diastolic BP were -8.6 and -4.6 mmHg, respectively (difference: -4.0
      mmHg; P < 0.0001). The percentage of patients achieving the BP target (<140/90 or
      <130/80 mmHg in the absence or presence of diabetes mellitus, respectively) was
      significantly higher with valsartan/amlodipine (79.0%) versus nifedipine GITS
      (57.4%; P < 0.0001). The overall incidence rate of adverse events was lower with
      valsartan/amlodipine (19.2%) than with nifedipine GITS (29.4%; P = 0.004).
      CONCLUSION: The valsartan/amlodipine 80/5 mg single-pill combination is well
      tolerated and more effective than nifedipine GITS 30 mg for BP control in Chinese
      patients with hypertension.

PMID- 23963550
TI  - What is convincing evidence on alcohol pricing?

PMID- 23963551
TI  - Hunt's priorities on entitlement to use the NHS are wrong.

PMID- 23963552
TI  - Scan the legs, not the lungs, in low risk patients with suspected pulmonary
      embolism.

PMID- 23963553
TI  - The accuracy of CT pulmonary angiography is not as high as purported.

PMID- 23963554
TI  - CT triple rule-out examination: higher radiation dose without clinical benefit.

PMID- 23963555
TI  - V/Q SPECT: the primary imaging test for suspected pulmonary embolism.

PMID- 23963556
TI  - Risk-benefit ratio favours treating all pulmonary emboli, no matter how small.

PMID- 23963557
TI  - Most patients with isolated subsegmental pulmonary embolism do not need
      anticoagulants.

PMID- 23963558
TI  - Authors' reply to Quantrill, Benger, Ripley and colleagues, Roach, Rogers, and
      Haldar and colleagues.

PMID- 23963559
TI  - Turning doctors into coders.

PMID- 23963560
TI  - Healthy behaviours yield major benefits in ageing.

PMID- 23963561
TI  - Science of overdiagnosis to be served up with a good dose of humility.

PMID- 23963562
TI  - How the friends and family test is conveyed to the public should be reconsidered.

PMID- 23963563
TI  - EFPIA-PhRMA's principles for clinical trial data sharing have been misunderstood.

PMID- 23963564
TI  - Concerted effort is needed to tackle health burden of sciatica and back pain.

PMID- 23963565
TI  - Hold on tight and be prepared to change in a few years.

PMID- 23963566
TI  - Risk of death found to be raised in chronic kidney disease patients with low
      diastolic blood pressure.

PMID- 23963567
TI  - Two UK people arrested for planning to take relative to Swiss suicide clinic.

PMID- 23963568
TI  - Court approves sterilisation of man with learning difficulties.

PMID- 23963569
TI  - Reducing the risk of foaming and decreasing viscosity by two-stage anaerobic
      digestion of sugar beet pressed pulp.
AB  - Anaerobic digestion (AD) of sugar beet pressed pulp (SBPP) is a promising
      treatment concept. It produces biogas as a renewable energy source making sugar
      production more energy efficient and it turns SBPP from a residue into a valuable
      resource. In this study one- and two-stage mono fermentation at mesophilic
      conditions in a continuous stirred tank reactor were compared. Also the optimal
      incubation temperature for the pre-acidification stage was studied. The fastest
      pre-acidification, with a hydraulic retention time (HRT) of 4 days, occurred at a
      temperature of 55  degrees C. In the methanogenic reactor of the two-stage system
      stable fermentation at loading rate of 7 kg VS/m3 d was demonstrated. No
      artificial pH adjustment was necessary to maintain optimum levels in both the pre
      acidification and the methanogenic reactor. The total HRT of the two-stage AD was
      36 days which is considerably lower compared to the one-stage AD (50 days). The
      frequently observed problem of foaming at high loading rates was less severe in
      the two-stage reactor. Moreover the viscosity of digestate in the methanogenic
      stage of the two-stage fermentation was in average tenfold lower than in the one
      stage fermentation. This decreases the energy input for the reactor stirring
      about 80 %. The observed advantages make the two-stage process economically
      attractive, despite higher investments for a two reactor system. 

PMID- 23963570
TI  - Hazards in determining whether a drug is hazardous.
AB  - The US National Institute for Occupational Safety and Health list and evaluation
      criteria have provided an important foundation to help institutions identify and
      create a list of hazardous formulary drugs. However, further guiding principles
      were needed to make the adoption feasible at our organization. First, we
      developed separate directives for determining the inherent hazardous toxicity of
      a drug and for the requirements for safe handling based on dosage forms (exposure
      risks) of these drugs. Secondly, we created a systematic approach in determining
      the scope of the drugs reviewed by US National Institute for Occupational Safety
      and Health. Thirdly, we streamlined our review process by defining which drugs
      needed to be evaluated by our organization. Finally, we considered the pros and
      cons of creating a tiered system for classifying hazardous drugs beyond those
      recommended by US National Institute for Occupational Safety and Health. 

PMID- 23963571
TI  - Determination of carbohydrates present in Saccharomyces cerevisiae using mid
      infrared spectroscopy and partial least squares regression.
AB  - A fast and simple method to control variations in carbohydrate composition of
      Saccharomyces cerevisiae, baker's yeast, during fermentation was developed using
      mid-infrared (mid-IR) spectroscopy. The method allows for precise and accurate
      determinations with minimal or no sample preparation and reagent consumption
      based on mid-IR spectra and partial least squares (PLS) regression. The PLS
      models were developed employing the results from reference analysis of the yeast
      cells. The reference analyses quantify the amount of trehalose, glucose,
      glycogen, and mannan in S. cerevisiae. The selection and optimization of
      pretreatment steps of samples such as the disruption of the yeast cells and the
      hydrolysis of mannan and glycogen to obtain monosaccharides were carried out.
      Trehalose, glucose, and mannose were determined using high-performance liquid
      chromatography coupled with a refractive index detector and total carbohydrates
      were measured using the phenol-sulfuric method. Linear concentration range,
      accuracy, precision, LOD and LOQ were examined to check the reliability of the
      chromatographic method for each analyte. 

PMID- 23963572
TI  - Select cytoplasmic and membrane proteins increase the percentage of immobile
      integrins but do not affect the average diffusion coefficient of mobile
      integrins.
AB  - Integrins are ubiquitous adhesion receptors that are important for signaling and
      integrating the extracellular matrix and cytoskeleton. The role of cytoplasmic
      proteins vinculin, focal adhesion kinase (FAK), integrin-linked kinase (ILK), and
      membrane proteins epidermal growth factor receptor (EGFR) and Notch in altering
      alphaPS2CbetaPS integrin lateral diffusion was measured using single particle
      tracking (SPT) and RNA interference (RNAi). SPT measures heterogeneous diffusion
      properties, and RNAi selectively reduces the concentration of a target protein.
      After systematically reducing the concentration of vinculin, FAK, ILK, EGFR, or
      Notch, there was a 31 to 80% increase in the mobile integrin fraction, indicating
      that these five targeted proteins (or assemblies that contain these proteins) are
      responsible for immobilizing a fraction of the integrins when all proteins are
      present at native concentrations. The average diffusion coefficient of all mobile
      integrins did not change after any of the RNAi treatments, and the percentage of
      Brownian, directed, or anomalous/constrained trajectories relative to total
      mobile trajectories did not change after vinculin or EGFR RNAi. However, the
      fraction of anomalous/constrained trajectories relative to the total mobile
      trajectories increased 9 to 19% after FAK, ILK, and Notch RNAi, when the
      concentration of these proteins was reduced. In the case of FAK, ILK, and Notch,
      native concentrations of these proteins simultaneously increase the immobile
      fraction of integrins but decrease the diffusion constraints to those integrins
      that remain mobile. Comparisons of single receptor and ensemble measurements of
      diffusion and what is known about the effect of these proteins in altering
      integrin clustering are discussed.

PMID- 23963573
TI  - An innovative strategy for direct electrochemical detection of microRNA
      biomarkers.
AB  - We report an electrochemical method for direct, reagentless, and label-free
      detection of microRNA, based on a conjugated copolymer, poly(5-hydroxy-1,4
      naphthoquinone-co-5-hydroxy-2-carboxyethyl-1,4-naphthoquinone), acting as
      hybridization transducer. Hybridization between the oligonucleotide capture probe
      and a microRNA target of 22 base pairs generates an increase in the redox current
      ("signal-on"), which is evidenced by square wave voltammetry. Selectivity is
      good, with little hybridization for non-complementary targets, and the limit of
      detection reaches 650 fM. It is also evidenced that this sensitivity benefits
      from the high affinity of DNA for RNA. 

PMID- 23963575
TI  - NADPH oxidase derived reactive oxygen species are involved in human neutrophil IL
      1beta secretion but not in inflammasome activation.
AB  - Neutrophils are essential players in acute inflammatory responses. Upon
      stimulation, neutrophils activate NADPH oxidase, generating an array of reactive
      oxygen species (ROS). Interleukin-1 beta (IL-1beta) is a major proinflammatory
      cytokine synthesized as a precursor that has to be proteolytically processed to
      become biologically active. The role of ROS in IL-1beta processing is still
      controversial and has not been previously studied in neutrophils. We report here
      that IL-1beta processing in human neutrophils is dependent on caspase-1 and on
      the serine proteases elastase and/or proteinase 3. NADPH oxidase deficient
      neutrophils activated caspase-1 and did not exhibit differences in NALP3
      expression, indicating that ROS are neither required for inflammasome activation
      nor for its priming, as has been reported for macrophages. Strikingly, ROS
      exerted opposite effects on the processing and secretion of IL-1beta; whereas ROS
      negatively controlled caspase-1 activity, as reported in mononuclear phagocytes,
      ROS were found to be necessary for the exportation of mature IL-1beta out of the
      cell, a role never previously described. The complex ROS-mediated regulation of
      neutrophil IL-1beta secretion might constitute a physiological mechanism to
      control IL-1beta-dependent inflammatory processes where neutrophils play a
      crucial role. 

PMID- 23963577
TI  - Coronary microvasculature: small vessels with large impact.

PMID- 23963578
TI  - Thoracic endovascular aortic repair for type B dissection: a ubiquitous treatment
      option?

PMID- 23963579
TI  - Ischemic conditioning as an adjunct to percutaneous coronary intervention.

PMID- 23963581
TI  - Letter by Karabay et al regarding article, "fractional flow reserve assessment of
      left main stenosis in the presence of downstream coronary stenoses".

PMID- 23963582
TI  - Response to letter regarding article, "fractional flow reserve assessment of left
      main stenosis in the presence of downstream coronary stenoses".

PMID- 23963584
TI  - Relapse prevention interventions for smoking cessation.
AB  - BACKGROUND: A number of treatments can help smokers make a successful quit
      attempt, but many initially successful quitters relapse over time. Several
      interventions have been proposed to help prevent relapse. OBJECTIVES: To assess
      whether specific interventions for relapse prevention reduce the proportion of
      recent quitters who return to smoking. SEARCH METHODS: We searched the Cochrane
      Tobacco Addiction Group trials register in May 2013 for studies mentioning
      relapse prevention or maintenance in title, abstracts or keywords. SELECTION
      CRITERIA: Randomized or quasi-randomized controlled trials of relapse prevention
      interventions with a minimum follow-up of six months. We included smokers who
      quit on their own, were undergoing enforced abstinence, or were participating in
      treatment programmes. We included trials that compared relapse prevention
      interventions with a no intervention control, or that compared a cessation
      programme with additional relapse prevention components with a cessation
      programme alone. DATA COLLECTION AND ANALYSIS: Studies were screened and data
      extracted by one review author, and checked by a second. Disagreements were
      resolved by discussion or by referral to a third review author. MAIN RESULTS:
      Sixty-three studies met inclusion criteria but were heterogeneous in terms of
      populations and interventions. We considered 41 studies that randomly assigned
      abstainers separately from studies that randomly assigned participants before
      their quit date.Upon looking at studies of behavioural interventions that
      randomly assigned abstainers, we detected no benefit of brief and 'skills-based'
      relapse prevention methods for women who had quit smoking because of pregnancy,
      or for smokers undergoing a period of enforced abstinence during hospitalisation
      or military training. We also failed to detect significant effects of behavioural
      interventions in trials in unselected groups of smokers who had quit on their own
      or through a formal programme. Amongst trials randomly assigning smokers before
      their quit date and evaluating the effects of additional relapse prevention
      components, we found no evidence of benefit of behavioural interventions or
      combined behavioural and pharmacotherapeutic interventions in any subgroup.
      Overall, providing training in skills thought to be needed for relapse avoidance
      did not reduce relapse, but most studies did not use experimental designs best
      suited to the task and had limited power to detect expected small differences
      between interventions. For pharmacological interventions, extended treatment with
      varenicline significantly reduced relapse in one trial (risk ratio (RR) 1.18, 95%
      confidence interval (CI) 1.03 to 1.36). Pooling of six studies of extended
      treatment with bupropion failed to detect a significant effect (RR 1.15, 95% CI
      0.98 to 1.35). Two small trials of oral nicotine replacement treatment (NRT)
      failed to detect an effect, but treatment compliance was low, and in two other
      trials of oral NRT in which short-term abstainers were randomly assigned, a
      significant effect of intervention was noted. AUTHORS' CONCLUSIONS: At the
      moment, there is insufficient evidence to support the use of any specific
      behavioural intervention to help smokers who have successfully quit for a short
      time to avoid relapse. The verdict is strongest for interventions focused on
      identifying and resolving tempting situations, as most studies were concerned
      with these. Little research is available regarding other behavioural
      approaches.Extended treatment with varenicline may prevent relapse. Extended
      treatment with bupropion is unlikely to have a clinically important effect.
      Studies of extended treatment with nicotine replacement are needed.

PMID- 23963583
TI  - Heart failure and tachycardia-induced cardiomyopathy.
AB  - Congestive heart failure is a major health care concern affecting almost six
      million Americans and an estimated 23 million people worldwide, and its
      prevalence is increasing with time. Long-standing tachycardia is a well
      recognized cause of heart failure and left ventricular dysfunction and has led to
      the nomenclature, tachycardia-induced cardiomyopathy. Tachycardia-induced
      cardiomyopathy is generally a reversible cardiomyopathy with effective treatment
      of the causative arrhythmia, either with medications, surgery, or catheter
      ablation. Tachycardia-induced cardiomyopathy remains poorly understood and is
      likely under-diagnosed. A better understanding of tachycardia-induced
      cardiomyopathy and improved recognition of its presence in clinical practice is
      vital to the health of patients with this disorder. The goal of this review is to
      discuss the pathogenesis and clinical manifestations of tachycardia-induced
      cardiomyopathy, as well as approaches to its diagnosis and treatment. 

PMID- 23963585
TI  - Constitutive expression of the K-domain of a Vaccinium corymbosum SOC1-like
      (VcSOC1-K) MADS-box gene is sufficient to promote flowering in tobacco.
AB  - KEY MESSAGE: The K-domain of a blueberry-derived SOC1 -like gene promotes
      flowering in tobacco without negatively impacting yield, demonstrating potential
      for manipulation of flowering time in horticultural crops. ABSTRACT: The
      SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) and SOC1-likes, belonging to
      the MIKC(c) (type II) MADS-box gene subfamily, are major floral activators and
      integrators of plant flowering. Both MADS-domains and K (Keratin)-domains are
      highly conserved in MIKC(c)-type MADS proteins. While there are many reports on
      overexpression of intact MIKC(c)-type MADS-box genes, few studies have been
      conducted to investigate the effects of the K-domains. In this report, a 474-bp K
      domain of Vaccinium SOC1-like (VcSOC1-K) was cloned from the cDNA library of the
      northern highbush blueberry (Vaccinium corymbosum L.). Functional analysis of the
      VcSOC1-K was conducted by ectopically expressing of 35S:VcSOC1-K in tobacco.
      Reverse transcription PCR confirmed expression of the VcSOC1-K in T0 plants.
      Phenotypically, T1 transgenic plants (10 T1 plants/event) flowered sooner after
      seeding, and were shorter with fewer leaves at the time of flowering, than
      nontransgenic plants; but seed pod production of transgenic plants was not
      significantly affected. These results demonstrate that overexpression of the K
      domain of a MIKC(c)-type MADS-box gene alone is sufficient to promote early
      flowering and more importantly without affecting seed production.

PMID- 23963586
TI  - Factors associated with fear-avoidance beliefs about low back pain.
AB  - BACKGROUND: Low back pain (LBP) is a common major health problem. Fear-avoidance
      beliefs are thought to be an important risk factor for chronic LBP. This study
      investigated factors associated with the Fear-Avoidance Beliefs Questionnaire
      (FABQ) scores of Japanese adults who experienced LBP. We focused on the
      association of FABQ scores with medical advice to rest and the experience of
      seeing family members and/or significant others with disabling LBP. METHODS: In
      February 2011, 1,063,083 adults aged 20-79 years who had registered as internet
      based research volunteers were randomly selected and invited to participate in a
      questionnaire survey. The data from 52,650 respondents who had experienced LBP
      were analyzed. Multiple linear regression analysis was used to examine the
      association between FABQ physical activity scores and the advice for respondents
      with LBP to rest, the experience of seeing others with disabling LBP, and other
      personal and LBP factors. RESULTS: After controlling for age, sex, and lifetime
      and current LBP disability grades, the experience of seeing others with disabling
      LBP (regression coefficient beta = 0.94), rest advice (beta = 0.91), history of
      chronic LBP (beta = 0.78), radiating pain below the knee (beta = 0.44), and
      workers' compensation (beta = 0.51) were associated with higher FABQ physical
      activity scores. Conversely, regular exercise (beta = -0.89) and LBP attributed
      to sports (beta = -0.76) were associated with lower FABQ physical activity
      scores. CONCLUSION: The association between rest advice and higher fear-avoidance
      beliefs supports the recent treatment guidelines that emphasize continuation of
      daily activities. STUDY DESIGN: cross-sectional study.

PMID- 23963587
TI  - Behavioral and neuropathological changes in animal models of chronic painful
      scar.
AB  - BACKGROUND: Long-lasting limb pain or back pain after surgery occasionally
      develops into chronic pain that leads to lower activity and a poorer quality of
      life for many patients. To determine the histopathological and neuropathological
      mechanisms that cause persistent post-operative pain, we developed an original
      animal model with sustained painful scars and then examined pain-related behavior
      and the pathological alteration of peripheral tissues and spinal nerves
      associated with the model. METHODS: The animal model (Scar group) was prepared in
      rats by extensively stripping subcutaneous tissue from the plantar in the hind
      paw followed by subsequent examination of pain-related behavior over the next 12
      weeks. Thereafter, we conducted histological staining of the scar tissues,
      immunohistochemical staining of c-Fos (L5 dorsal horn), and electron microscopic
      analysis of the L5 spinal nerve fibers/dorsal roots. RESULTS: The mechanical pain
      threshold decreased specifically in the ipsilateral plantar in animals with scar.
      This state was maintained for 12 weeks. A collagen layer developed from fibers
      derma to the muscular layer in the scar tissue in which many fibroblasts were
      observed. No statistical differences were found for the areas of the c-Fos
      immunoreactive (c-Fos-IR) neurons in the ipsilateral and contralateral sides of
      the L5 level of the dorsal horn in both the Scar group and Pinhole (sham
      operation) group. However, myelin sheath fragmentation of the nerve fibers was
      observed in the ipsilateral dorsal root at the L5 position. CONCLUSIONS: We
      created a persistent painful scar model through extensive injury of the
      peripheral tissues. Fibrotic thickening of the cutaneous tissues, possible
      sensitization, and partial degradation of the spinal nerve related to the painful
      scar were observed. This model should enable us to better understand the
      mechanism of sensitization caused by painful scar and investigate new methods for
      treating painful scars in humans.

PMID- 23963589
TI  - Results at a minimum of 10 years of follow-up for AMS and PerFix HA-coated
      cementless total hip arthroplasty: impact of cross-linked polyethylene on implant
      longevity.
AB  - PURPOSE: The purpose of this study was to report results at a minimum of 10 years
      for hydroxyapatite (HA) coating on the titanium arc-sprayed cementless total hip
      arthroplasty (THA) and to evaluate the impact of cross-linked polyethylene (XLPE)
      on implant longevity. METHODS: A total of 131 consecutive primary THAs in 123
      patients using an AMS acetabular cup and a PerFix HA stem were retrospectively
      reviewed. Conventional PE was used for 62 hips (CPE group) and cross-linked PE
      for 69 hips (XLPE group), with mean follow-up periods of 13 and 11.5 years,
      respectively. These patients were reviewed using the Japanese Orthopaedic
      Association (JOA) Hip Score and evaluated in terms of PE wear, osteolysis, and
      implant survival. RESULTS: The JOA score improved from 42.6 to 83.9 points at the
      final follow-up. The mean wear rate of 0.12 mm/year in the CPE group was
      significantly greater than that of XLPE at 0.007 mm/year. In the CPE group, ten
      (16.1 %) and two (3.2 %) hips, respectively, underwent PE exchange due to severe
      wear and acetabular revision due to loosening associated with osteolysis. Three
      patients had revision in the XLPE group: one cup for aseptic loosening, one PE
      for recurrent dislocation, and one stem for neck fracture. No evident osteolysis
      was seen in the XLPE group. Kaplan-Meier survivorship with any revision as the
      end point shows that the 12-year survival rate was 97.7 % for cups, 93.8 % for PE
      liners, and 99.2 % for stems. Multivariate analysis revealed that the use of XLPE
      significantly reduced the risk of revision, with the odds ratio (OR) of 4.3.
      CONCLUSIONS: AMS and PerFix HA components in this series show excellent implant
      fixation; however, high rates of PE wear and subsequent osteolysis were limiting
      factors in long-term success. Low wear rates with XLPE suggest improved implant
      longevity.

PMID- 23963588
TI  - Prevalence of lumbar spinal stenosis, using the diagnostic support tool, and
      correlated factors in Japan: a population-based study.
AB  - BACKGROUND: Few studies have examined the prevalence of lumbar spinal stenosis
      (LSS) in the general population. The purposes of this study were to estimate the
      prevalence of LSS and to investigate correlated factors for LSS in Japan.
      METHODS: A questionnaire survey was performed on 4,400 subjects selected from
      residents aged 40-79 years in Japan by stratified two-stage random sampling in
      2010. The question items consisted of lower-limb symptoms suggestive of LSS, the
      diagnostic support tool for LSS (LSS-DST), demographic and lifestyle
      characteristics, comorbidities, the Japanese Perceived Stress Scale (JPSS), and
      the Mental Health Index 5 (MHI-5). Using the LSS-DST, the presence of LSS was
      predicted to estimate the prevalence of LSS. Logistic regression analysis was
      performed to examine the relationship between LSS and correlated factors.
      RESULTS: Questionnaires were obtained from 2,666 subjects (60.6 %), consisting of
      1,264 males (47.4 %). The mean (standard deviation) age was 60.0 (10.9) years.
      According to the LSS-DST, 153 subjects were regarded as having LSS. The
      prevalence was estimated to be 5.7 %. When standardizing this value with the age
      distribution of the Japanese population, it was estimated that 3,650,000 Japanese
      subjects aged 40-79 years might have LSS using the LSS-DST. Prevalence increased
      with age and was particularly high in subjects aged 70-79 years, irrespective of
      gender. As correlated factors, an advanced age (60 years or older), diabetes
      mellitus, urological disorders, and osteoarthritis/fracture as comorbidities, and
      depressive symptoms, were associated with LSS. CONCLUSIONS: This study elucidated
      the prevalence of LSS and factors associated with LSS in Japan. This is the first
      report describing the estimated prevalence of LSS and associated factors using a
      strictly sampled representative population.

PMID- 23963590
TI  - Leg length discrepancy and lower limb alignment after total hip arthroplasty in
      unilateral hip osteoarthritis patients.
AB  - BACKGROUND: Leg length discrepancy (LLD) following total hip arthroplasty (THA)
      is a leading cause of patient dissatisfaction. However, no reports have described
      the influence of lower limb alignment on LLD after THA. In the present study, we
      firstly investigated the change in lower limb alignment after THA. Secondly, we
      determined the influence of lower limb alignment on LLD after THA. Thirdly, we
      evaluated the influence of LLD in the entire lower leg on the clinical outcomes
      after THA. METHODS: We followed up with 54 unilateral hip osteoarthritis (OA)
      patients 1 year after THA. For the radiological assessment of LLD and lower limb
      alignment, we obtained anteroposterior radiographs of the pelvis and both lower
      legs in entirety in a standing position before and 1 year after THA. The Harris
      Hip Score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC), and Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36) were
      also obtained to assess the clinical outcome. RESUTS: The alignment of the
      affected leg, which was more valgus than the unaffected leg before THA, tended
      toward varus after THA, and the discrepancy between the lower limb alignments on
      both sides decreased. However, the alignment discrepancies that remained after
      THA influenced the LLD measured on the radiograph of the entire lower leg, and
      this LLD influenced the clinical outcome as measured by the HHS and the WOMAC
      score. CONCLUSIONS: LLD in the entire lower leg should be corrected for a better
      clinical outcome after THA.

PMID- 23963591
TI  - Neuromagnetic oscillations predict evoked-response latency delays and core
      language deficits in autism spectrum disorders.
AB  - Previous studies have observed evoked response latency as well as gamma band
      superior temporal gyrus (STG) auditory abnormalities in individuals with autism
      spectrum disorders (ASD). A limitation of these studies is that associations
      between these two abnormalities, as well as the full extent of oscillatory
      phenomena in ASD in terms of frequency and time, have not been examined. Subjects
      were presented pure tones at 200, 300, 500, and 1,000 Hz while
      magnetoencephalography assessed activity in STG auditory areas in a sample of 105
      children with ASD and 36 typically developing controls (TD). Findings revealed a
      profile such that auditory STG processes in ASD were characterized by pre
      stimulus abnormalities across multiple frequencies, then early high-frequency
      abnormalities followed by low-frequency abnormalities. Increased pre-stimulus
      activity was a 'core' abnormality, with pre-stimulus activity predicting post
      stimulus neural abnormalities, group membership, and clinical symptoms (CELF-4
      Core Language Index). Deficits in synaptic integration in the auditory cortex are
      associated with oscillatory abnormalities in ASD as well as patient symptoms.
      Increased pre-stimulus activity in ASD likely demonstrates a fundamental signal
      to-noise deficit in individuals with ASD, with elevations in oscillatory activity
      suggesting an inability to maintain an appropriate 'neural tone' and an inability
      to rapidly return to a resting state prior to the next stimulus. 

PMID- 23963592
TI  - Brief report: problem solving therapy in college students with autism spectrum
      disorders: feasibility and preliminary efficacy.
AB  - Students with autism spectrum disorder (ASD), though academically capable, can
      have difficulty succeeding in college. Evidence-based intervention to promote
      effective problem solving may improve quality of life, as well as success and
      satisfaction in college. This study adapted and piloted a group-based cognitive
      behavioral intervention program, Problem Solving Skills: 101 (PSS: 101), to teach
      effective problem solving ability in college students with ASD. Therapists met
      all treatment integrity objectives across sessions, four of the five participants
      completed at least eight of the nine sessions, and between-session assignments
      were generally completed (83 % completion rate), indicating a high level of
      treatment adherence. Two participants demonstrated reliable improvement post
      intervention in problem solving ability and subjective distress. Further
      evaluation to assess efficacy of the intervention is warranted.

PMID- 23963594
TI  - Binder-free graphene foams for O2 electrodes of Li-O2 batteries.
AB  - We report a novel method to prepare bind-free graphene foams as O2 electrodes for
      Li-O2 batteries. The graphene foams are synthesized by electrochemical leavening
      of the graphite papers, followed by annealing in inert gas to control the amount
      of structural defects in the graphene foams. It was found that the structural
      defects were detrimental to the processes of the ORR and OER in Li-O2 batteries.
      The round-trip efficiencies and the cycling stabilities of the graphene foams
      were undermined by the structural defects. For example, the as-prepared graphene
      foam with a high defect level (ID/IG = 0.71) depicted a round-trip efficiency of
      only 0.51 and a 20(th)-cycle discharge capacity of only 340 mA h g(-1) at a
      current density of 100 mA g(-1). By contrast, the graphene foam electrode
      annealed at 800  degrees C with ID/IG = 0.07 delivered a round-trip efficiency of
      up to 80% with a stable discharge voltage at ~2.8 V and a stable charge voltage
      below 3.8 V for 20 cycles. According to the analysis on the electrodes after 20
      cycles, the structural defects led to the quickened decay of the graphene foams
      and boosted the formation of side products.

PMID- 23963593
TI  - Joint analysis of band-specific functional connectivity and signal complexity in
      autism.
AB  - Examination of resting state brain activity using electrophysiological measures
      like complexity as well as functional connectivity is of growing interest in the
      study of autism spectrum disorders (ASD). The present paper jointly examined
      complexity and connectivity to obtain a more detailed characterization of resting
      state brain activity in ASD. Multi-scale entropy was computed to quantify the
      signal complexity, and synchronization likelihood was used to evaluate functional
      connectivity (FC), with node strength values providing a sensor-level measure of
      connectivity to facilitate comparisons with complexity. Sensor level analysis of
      complexity and connectivity was performed at different frequency bands computed
      from resting state MEG from 26 children with ASD and 22 typically developing
      controls (TD). Analyses revealed band-specific group differences in each measure
      that agreed with other functional studies in fMRI and EEG: higher complexity in
      TD than ASD, in frontal regions in the delta band and occipital-parietal regions
      in the alpha band, and lower complexity in TD than in ASD in delta (parietal
      regions), theta (central and temporal regions) and gamma (frontal-central
      boundary regions); increased short-range connectivity in ASD in the frontal lobe
      in the delta band and long-range connectivity in the temporal, parietal and
      occipital lobes in the alpha band. Finally, and perhaps most strikingly, group
      differences between ASD and TD in complexity and FC appear spatially
      complementary, such that where FC was elevated in ASD, complexity was reduced
      (and vice versa). The correlation of regional average complexity and connectivity
      node strength with symptom severity scores of ASD subjects supported the overall
      complementarity (with opposing sign) of connectivity and complexity measures,
      pointing to either diminished connectivity leading to elevated entropy due to
      poor inhibitory regulation or chaotic signals prohibiting effective measure of
      connectivity. 

PMID- 23963595
TI  - Improved pixel-by-pixel MRI R2* relaxometry by nonlocal means.
AB  - PURPOSE: To investigate the feasibility of improving MRI R2* mapping by filtering
      the images before curve-fitting. METHODS: Pixel-by-pixel curve-fitting for the
      quantification of MRI relaxometry remains a challenge for low signal-to-noise
      ratio images. By computing the weighted mean of spatially adjacent pixels, the
      low-pass Gaussian (LPG) filter can suppress the noise but at the expense of
      blurring. By assigning high weights to pixels with similar neighborhood patches,
      the nonlocal means (NLM) algorithm can reduce noise while retaining intrinsic
      signals, however, its potential has not been explored in pixel-by-pixel MRI
      relaxometry, and in this study, we aimed to investigate the impact of the LPG and
      the NLM filtering on decay signals and MRI R2* mapping. These two filtering
      methods were compared on both simulated and in vivo data. RESULTS: Both LPG and
      NLM algorithms produces R2* maps with decreased root-mean-square-errors. The LPG
      filter blurs edges of R2* maps while the NLM algorithm preserves details well.
      The NLM consistently yields R2* mapping with smaller errors than the LPG
      filtering in all cases. CONCLUSION: Pixel-by-pixel fitting can skew MRI
      relaxometry. The NLM outperforms the conventional LPG filter and has the
      potential to provide more accurate pixel-by-pixel MRI relaxometry for improved
      tissue characterization.

PMID- 23963596
TI  - Neu-p11 reduces clock/apelin expression in insulin-resistant mouse adipocyte
      model.

PMID- 23963597
TI  - Patterns and determinants of physical activity among Saudi adolescents.
AB  - BACKGROUND: Few studies have reported comprehensive and valid physical activity
      (PA) data for Saudi youth. Therefore, the purpose of this study was to examine
      patterns and determinants of PA among Saudi adolescents. METHODS: A cross
      sectional study was conducted in Saudi secondary schools (15-19 years) during
      2009/2010 and used multistage stratified cluster sample (N = 2866, 51.7%
      females). Weight, height, sedentary behaviors, PA, and dietary habits were
      assessed. RESULTS: Roughly 44% of males and 20% of females were active (>= 1
      hour/day). Males in public schools were more active than in private schools,
      whereas the opposite was true for females. Females exercise mostly at home,
      whereas males exercise at public places. The majority of females exercise alone
      or with relatives, whereas males largely exercise with friends. Males were active
      for health and recreation whereas females were active for weight loss and
      recreation. Lack of time was the primary reason for inactivity in both sexes. The
      predictors of total PA time were gender, intakes of fruit, milk, energy drinks
      and vegetables and waist/height ratio (R2 = 0.145). CONCLUSIONS: The high
      inactivity levels, especially among females, are of great concern. Promotion of
      active living among youth should be a national public health priority.

PMID- 23963598
TI  - Evaluating gender differences in prognosis following SPECT myocardial perfusion
      imaging among patients with diabetes and known or suspected coronary disease in
      the modern era.
AB  - BACKGROUND: Previous data suggested that diabetic women were at greater risk for
      future cardiac events than diabetic men. Increasing awareness of coronary artery
      disease (CAD) in women and advances in the management of CAD may have changed
      this paradigm. OBJECTIVE: To investigate gender differences in prognosis among
      patients with diabetes who were clinically referred for single-photon emission
      computed tomography myocardial perfusion imaging (SPECT-MPI). METHODS: Patients
      with diabetes undergoing SPECT-MPI from 1996 to 2006 were followed for 5 years or
      until cardiac death or non-fatal myocardial infarction. Clinical characteristics
      and nuclear parameters were compared with chi (2) and t tests. Multivariable Cox
      regression controlled for baseline differences and tested the impact of gender on
      survival. RESULTS: A total of 4,628 SPECT-MPI patients with diabetes (50% women,
      mean age 63 +/- 12 years) were analyzed. There were 380 events, with rates higher
      in men (10% vs 7%, P < .001). Patients of either gender with abnormal scans had
      higher event rates than patients with normal scans. There were fewer cardiac
      events in diabetic females with no known CAD and normal scans compared to similar
      males (P = .044). However, diabetic males and females with known CAD had similar
      event rates for all degrees of perfusion abnormalities. Only age, history of
      heart failure, nuclear perfusion defect, and LVEF predicted survival; gender did
      not. LVEF <= 50% had the strongest association with cardiac events (hazard ratio
      = 2.518, 95% confidence interval, 1.922-3.298). CONCLUSION: Cardiovascular
      outcomes among patients with diabetes, regardless of a history of CAD, were
      similar in women and men. The size and severity of stress-induced perfusion
      abnormalities predicted outcomes equally in both genders.

PMID- 23963600
TI  - Effects of acquisition time and reconstruction algorithm on image quality,
      quantitative parameters, and clinical interpretation of myocardial perfusion
      imaging.
AB  - BACKGROUND: Recently introduced iterative reconstruction algorithms with
      resolution recovery (RR) and noise-reduction technology seem promising for
      reducing scan time or radiation dose without loss of image quality. However, the
      relative effects of reduced acquisition time and reconstruction software have not
      previously been reported. The aim of the present study was to investigate the
      influence of reduced acquisition time and reconstruction software on quantitative
      and qualitative myocardial perfusion single photon emission computed tomography
      (SPECT) parameters using full time (FT) and half time (HT) protocols and
      Evolution for Cardiac Software. METHODS: We studied 45 consecutive, non-selected
      patients referred for a clinically indicated routine 2-day stress/rest (99m)Tc
      Sestamibi myocardial perfusion SPECT. All patients underwent an FT and an HT
      scan. Both FT and HT scans were processed according to our standard procedure
      with both ordered-subset expectation maximization (OSEM) + filtered back
      projection (FBP) reconstructions and a second reconstruction of HT scans was
      performed with the RR software producing three datasets for each patient for
      visual analysis (FT-OSEM, HT-OSEM, and HT-RR) and for quantitative analysis (FT
      FBP, HT-FBP, and HT-RR). The datasets were analyzed using commercially available
      QGS/QPS software and read by two observers evaluating image quality and clinical
      interpretation. Image quality was assessed on a 10-cm visual analog scale score.
      RESULTS: HT imaging was associated with loss of image quality that was
      compensated for by RR reconstruction. HT imaging was also associated with
      increasing perfusion defect extents, an effect more pronounced using RR than FBP
      reconstruction. Compared to standard FT-FBP, HT-RR significantly reduced left
      ventricular volumes whereas HT-FBP increased end-systolic volume. HT imaging had
      no effect on measured left ventricular ejections fraction or measures of
      reversibility. Image interpretation found a higher level of concordance between
      FT-OSEM and HT-RR than between FT-OSEM and HT-OSEM without any observable
      systematic effects. CONCLUSIONS: Use of RR reconstruction algorithms compensates
      for loss of image quality associated with reduced scan time. Both HT acquisition
      and RR reconstruction algorithm had significant effects on motion and perfusion
      parameters obtained with standard software, but these effects were relatively
      small and probably of limited clinical importance. Although no systematic effects
      on image interpretation were observed, the influence on diagnostic accuracy
      remains to be determined.

PMID- 23963599
TI  - Lessons learned from MPI and physiologic testing in randomized trials of stable
      ischemic heart disease: COURAGE, BARI 2D, FAME, and ISCHEMIA.
AB  - There is a preponderance of evidence that, in the setting of an acute coronary
      syndrome, an invasive approach using coronary revascularization has a morbidity
      and mortality benefit. However, recent stable ischemic heart disease (SIHD)
      randomized clinical trials testing whether the addition of coronary
      revascularization to guideline-directed medical therapy (GDMT) reduces death or
      major cardiovascular events have been negative. Based on the evidence from these
      trials, the primary role of GDMT as a front line medical management approach has
      been clearly defined in the recent SIHD clinical practice guideline; the role of
      prompt revascularization is less precisely defined. Based on data from
      observational studies, it has been hypothesized that there is a level of ischemia
      above which a revascularization strategy might result in benefit regarding
      cardiovascular events. However, eligibility for recent negative trials in SIHD
      has mandated at most minimal standards for ischemia. An ongoing randomized trial
      evaluating the effectiveness of randomization of patients to coronary angiography
      and revascularization as compared to no coronary angiography and GDMT in patients
      with moderate-severe ischemia will formally test this hypothesis. The current
      review will highlight the available evidence including a review of the published
      and ongoing SIHD trials. 

PMID- 23963601
TI  - Power graph compression reveals dominant relationships in genetic transcription
      networks.
AB  - We introduce a framework for the discovery of dominant relationship patterns in
      transcription networks, by compressing the network into a power graph with
      overlapping power nodes. Our application of this approach to the transcription
      networks of S. cerevisiae and E. coli, paired with GO term enrichment analysis,
      provides a highly informative overview of the most prominent relationships in the
      gene regulatory networks of these two organisms. 

PMID- 23963602
TI  - Supramodal and modality-sensitive representations of perceived action categories
      in the human brain.
AB  - Seeing Suzie bite an apple or reading the sentence 'Suzie munched the apple' both
      convey a similar idea. But is there a common neural basis for action
      comprehension when generated through video or text? The current study used
      functional magnetic resonance imaging to address this question. Participants
      observed videos or read sentences that described two categories of actions:
      eating and cleaning. A conjunction analysis of video and sentence stimuli
      revealed that cleaning actions (compared to eating actions) showed a greater
      response in dorsal frontoparietal regions, as well as within the medial fusiform
      gyrus. These findings reveal supramodal representations of perceived actions in
      the human brain, which are specific to action categories and independent of input
      modality (video or written words). In addition, some brain regions associated
      with cleaning and eating actions showed an interaction with modality, which was
      manifested as a greater sensitivity for video compared with sentence stimuli.
      Together, this pattern of results demonstrates both supramodal and modality
      sensitive representations of action categories in the human brain, a finding with
      implications for how we understand other people's actions from video and written
      sources. 

PMID- 23963603
TI  - Effects of structural and functional cerebellar lesions on sensorimotor
      adaptation of saccades.
AB  - The cerebellum is critically involved in the adaptation mechanisms that maintain
      the accuracy of goal-directed acts such as saccadic eye movements. Two categories
      of saccades, each relying on different adaptation mechanisms, are defined:
      reactive (externally triggered) saccades and voluntary (internally triggered)
      saccades. The contribution of the medio-posterior part of the cerebellum to
      reactive saccades adaptation has been clearly demonstrated, but the evidence that
      other parts of the cerebellum are also involved is limited. Moreover, the
      cerebellar substrates of voluntary saccades adaptation have only been marginally
      investigated. Here, we addressed these two questions by investigating the
      adaptive capabilities of patients with cerebellar or pre-cerebellar stroke. We
      recruited three groups of patients presenting focal lesions located,
      respectively, in the supero-anterior cerebellum, the infero-posterior cerebellum
      and the lateral medulla (leading to a Wallenberg syndrome including motor
      dysfunctions similar to those resulting from lesion of the medio-posterior
      cerebellum). Adaptations of reactive saccades and of voluntary saccades were
      tested during separate sessions in all patients and in a group of healthy
      participants. The functional lesion of the medio-posterior cerebellum in
      Wallenberg syndrome strongly impaired the adaptation of both reactive and
      voluntary saccades. In contrast, patients with lesion in the supero-anterior part
      of the cerebellum presented a specific adaptation deficit of voluntary saccades.
      Finally, patients with an infero-posterior cerebellar lesion showed mild
      adaptation deficits. We conclude that the medio-posterior cerebellum is critical
      for the adaptation of both saccade categories, whereas the supero-anterior
      cerebellum is specifically involved in the adaptation of voluntary saccades. 

PMID- 23963604
TI  - Generation of VHH antibodies against the Arabidopsis thaliana seed storage
      proteins.
AB  - Antibodies and antibody derived fragments are excellent tools for the detection
      and purification of proteins. However, only few antibodies targeting Arabidopsis
      seed proteins are currently available. Here, we evaluate the process to make
      antibody libraries against crude protein extracts and more particularly to
      generate a VHH phage library against native Arabidopsis thaliana seed proteins.
      After immunising a dromedary with a crude Arabidopsis seed extract, we cloned the
      single-domain antigen-binding fragments from their heavy-chain only antibodies in
      a phage display vector and selected nanobodies (VHHs) against native Arabidopsis
      seed proteins. For 16 VHHs, the corresponding antigens were identified by
      affinity purification and MS/MS analysis. They were shown to bind the major
      Arabidopsis seed storage proteins albumin and globulin (14 to albumin and 2 to
      globulin). All 16 VHHs were suitable primary reagents for the detection of the
      Arabidopsis seed storage proteins by ELISA. Furthermore, several of the anti
      albumin VHHs were used successfully for storage protein localisation via electron
      microscopy. The easy cloning, selection and production, together with the
      demonstrated functionality and applicability, strongly suggest that the VHH
      antibody format will play a more prominent role in future protein research, in
      particular for the study of native proteins. 

PMID- 23963605
TI  - Intestinal expression of metal transporters in Wilson's disease.
AB  - In Wilson's disease (WND), biallelic ATP7B gene mutation is responsible for
      pathological copper accumulation in the liver, brain and other organs. It has
      been proposed that copper transporter 1 (CTR1) and the divalent metal transporter
      1 (DMT1) translocate copper across the human intestinal epithelium, while Cu
      ATPases: ATP7A and ATP7B serve as copper efflux pumps. In this study, we
      investigated the expression of CTR1, DMT1 and ATP7A in the intestines of both WND
      patients and healthy controls to examine whether any adaptive mechanisms to
      systemic copper overload function in the enterocytes. Duodenal biopsy samples
      were taken from 108 patients with Wilson's disease and from 90 controls. CTR1,
      DMT1, ATP7A and ATP7B expression was assessed by polymerase chain reaction and
      Western blot. Duodenal CTR1 mRNA and protein expression was decreased in WND
      patients in comparison to control subjects, while ATP7A mRNA and protein
      production was increased. The variable expression of copper transporters may
      serve as a defense mechanism against systemic copper overload resulting from
      functional impairment of ATP7B. 

PMID- 23963607
TI  - Episodic movement disorders: from phenotype to genotype and back.
AB  - Episodic dyskinetic movement disorders are a heterogeneous group of rare
      conditions. Paroxysmal dyskinesias constitute the core of this group and usually
      exhibit normal interepisodic neurologic findings. Contrariwise, episodic
      dyskinesias occur as a particular feature of complex chronic neurologic
      disorders. Conjunction of accurate phenotyping with up-to-date methods of
      molecular genetics recently provided remarkable new insights concerning the
      genetic causes of episodic dyskinesia. The identification of heterozygous
      mutations in the PRRT2 gene in paroxysmal kinesigenic dyskinesia as well as in
      benign familial infantile seizures linked episodic movement disorders with
      epilepsy. Alternating hemiplegia of childhood, the prototype of a chronic
      multisystem disease with episodic dyskinesia as a clinical hallmark, was recently
      found to be caused by heterozygous de novo mutations in the ATP1A3 gene. The
      clinical spectra of PRRT2 as well as of ATP1A3 mutations are still expanding.
      This review summarizes new genetic findings and clinical aspects in episodic
      dyskinesias. 

PMID- 23963608
TI  - Poor oral health as a chronic, potentially modifiable dementia risk factor:
      review of the literature.
AB  - Poor oral health, including caries, tooth loss, and periodontitis, is ubiquitous
      worldwide, and is potentially treatable and preventable. Like adverse oral health
      conditions, Alzheimer disease and related disorders are also very common among
      aging populations. Established risk factors for Alzheimer disease include
      cerebrovascular disease and its vascular risk factors, many of which share
      associations with evidence of systemic inflammation also identified in
      periodontitis and other poor oral health states. In this review, we present
      epidemiologic evidence of links between poor oral health and both prevalent and
      incident cognitive impairment, and review plausible mechanisms linking these
      conditions, including evidence from compelling animal models. Considering that a
      large etiologic fraction of dementia remains unexplained, these studies argue for
      further multidisciplinary research between oral health conditions, including
      translational, epidemiologic, and possibly clinical treatment studies.

PMID- 23963611
TI  - Automated audiometry using apple iOS-based application technology.
AB  - OBJECTIVE: The aim of this study is to determine the feasibility of an Apple iOS
      based automated hearing testing application and to compare its accuracy with
      conventional audiometry. STUDY DESIGN: Prospective diagnostic study. Setting
      Academic medical center. SUBJECTS AND METHODS: An iOS-based software application
      was developed to perform automated pure-tone hearing testing on the iPhone, iPod
      touch, and iPad. To assess for device variations and compatibility, preliminary
      work was performed to compare the standardized sound output (dB) of various Apple
      device and headset combinations. Forty-two subjects underwent automated iOS-based
      hearing testing in a sound booth, automated iOS-based hearing testing in a quiet
      room, and conventional manual audiometry. RESULTS: The maximum difference in
      sound intensity between various Apple device and headset combinations was 4 dB.
      On average, 96% (95% confidence interval [CI], 91%-100%) of the threshold values
      obtained using the automated test in a sound booth were within 10 dB of the
      corresponding threshold values obtained using conventional audiometry. When the
      automated test was performed in a quiet room, 94% (95% CI, 87%-100%) of the
      threshold values were within 10 dB of the threshold values obtained using
      conventional audiometry. Under standardized testing conditions, 90% of the
      subjects preferred iOS-based audiometry as opposed to conventional audiometry.
      CONCLUSION: Apple iOS-based devices provide a platform for automated air
      conduction audiometry without requiring extra equipment and yield hearing test
      results that approach those of conventional audiometry.

PMID- 23963610
TI  - Sodium metavanadate exhibits carcinogenic tendencies in vitro in immortalized
      human bronchial epithelial cells.
AB  - Pentavalent vanadium compounds induce intracellular changes in vitro that are
      consistent with those of other carcinogenic substances. While there is no clear
      evidence that vanadium compounds cause cancer in humans, vanadium pentoxide
      causes lung cancer in rodents after long-term inhalation exposures and in turn
      IARC has categorized it as a group 2B possible human carcinogen. The goal of this
      study was to investigate the carcinogenicity of NaVO3 in the human immortalized
      bronchial epithelial cell line, Beas-2B. Cells were treated with 10 MUM NaVO3 for
      5 weeks, with or without recovery time, followed by gene expression microarray
      analysis. In a separate experiment, cells were exposed to 1-10 MUM NaVO3 for 4
      weeks and then grown in soft agar to test for anchorage-independent growth. A
      dose-dependent increase in the number of colonies was observed. In scratch tests,
      NaVO3-transformed clones could repair a wound faster than controls. In a gene
      expression microarray analysis of soft agar clones there were 2010 differentially
      expressed genes (DEG) (adjusted p-value <= 0.05) in NaVO3-transformed clones
      relative to control clones. DEG from this experiment were compared with the DEG
      of 5 week NaVO3 exposure with or without recovery, all with adjusted p-values <
      0.05, and 469 genes were altered in the same direction for transformed clones, 5
      week NaVO3-treated cells, and the recovered cells. The data from this study imply
      that chronic exposure to NaVO3 causes changes that are consistent with cellular
      transformation including anchorage-independent growth, enhanced migration
      ability, and gene expression changes that were likely epigenetically inherited. 

PMID- 23963612
TI  - Tracheocutaneous fistula closure in the pediatric population: should secondary
      closure be the standard of care?
AB  - OBJECTIVE: Tracheocutaneous fistula (TCF) closure is achieved by excision
      followed either by primary closure or healing by secondary intention. Although
      primary closure provides immediate resolution of the fistula, it is associated
      with more severe potential complications. Healing by secondary intention
      minimizes these potential complications; however, it is inconvenient for the
      patient and may be more likely to require revision surgery. We have had 2 life
      threatening complications after primary closure, and as a result, we largely
      changed our practice pattern. We compared complication and success rates of the 2
      methods since this change to determine its ramifications. STUDY DESIGN:
      Historical cohort study. SETTING: Academic tertiary care pediatric otolaryngology
      practice. Subjects and Methods Two hundred sixteen patients who underwent TCF
      closure between January 2004 and August 2012. RESULTS: Forty-six (21.3%) fistulae
      were addressed by primary closure, and 170 (78.7%) were addressed by secondary
      intention. The complication and revision rates were not significantly different
      between the 2 methods (8.7% vs 10% and 8.7% vs 14.7%, respectively). CONCLUSION:
      In our study, we did not see any statistical differences between the 2 methods
      studied but could not exclude clinically important differences that may have
      favored one method over the other. Although our comparative results were
      inconclusive, we have adopted secondary closure as standard practice for
      management of pediatric TCF. Individual surgeons and patients may use the data
      presented to help guide decisions concerning which procedure is most appropriate.

PMID- 23963609
TI  - The functional anatomy of impulse control disorders.
AB  - Impulsive-compulsive disorders such as pathological gambling, hypersexuality,
      compulsive eating, and shopping are side effects of the dopaminergic therapy for
      Parkinson's disease. With a lower prevalence, these disorders also appear in the
      general population. Research in the last few years has discovered that these
      pathological behaviors share features similar to those of substance use disorders
      (SUD), which has led to the term "behavioral addictions". As in SUDs, the
      behaviors are marked by a compulsive drive toward and impaired control over the
      behavior. Furthermore, animal and medication studies, research in the Parkinson's
      disease population, and neuroimaging findings indicate a common neurobiology of
      addictive behaviors. Changes associated with addictions are mainly seen in the
      dopaminergic system of a mesocorticolimbic circuit, the so-called reward system.
      Here we outline neurobiological findings regarding behavioral addictions with a
      focus on dopaminergic systems, relate them to SUD theories, and try to build a
      tentative concept integrating genetics, neuroimaging, and behavioral results.

PMID- 23963613
TI  - Chemiluminescent logic gates based on functionalized gold nanoparticles/graphene
      oxide nanocomposites.
AB  - Label-free logic gates (AND, OR, and INHIBIT) based on chemiluminescence (CL) as
      new optical readout signal have been developed by taking advantage of the unique
      CL activity of luminol- and lucigenin-functionalized gold nanoparticles/graphene
      oxide (luminol-lucigenin/AuNPs/GO) nanocomposites. It was found that Fe(2+) ions
      could induce the CL emission of luminol-lucigenin/AuNPs/GO nanocomposites in
      alkaline solution. On this basis, by using Fe(2+) ions and NaOH as the inputs and
      the CL signal as the output, an AND logic gate was fabricated. When the initial
      reaction system contained luminol-lucigenin/AuNPs/GO nanocomposites and NaOH,
      either Fe(2+) ions or Ag(+) ions could react with the luminol-lucigenin/AuNPs/GO
      nanocomposites to produce a strong CL emission. This result was used to design an
      OR logic gate using Fe(2+) ions and Ag(+) ions as the inputs and CL signal as the
      output. Moreover, two INHIBIT logic gates for Fe(2+) and Ag(+) were also
      developed using by NaClO and L-cysteine as their CL inhibitors, respectively.
      Furthermore, the proposed logic gates were successfully used to detect Fe(2+),
      Ag(+), and L-cysteine, respectively. The developed logic gates may find future
      applications in sensing, clinical diagnostics, and environmental monitoring.

PMID- 23963614
TI  - Nano-pipette directed transport of nanotube transmembrane channels and hybrid
      vesicles.
AB  - Using computational modeling, we simulate the interactions between a nanopipette
      and transmembrane, end-functionalized nanotubes that are localized within flat
      bilayers or nanoscopic vesicles. The functional groups (hairs) provide a "handle"
      for the moving pipette to controllably pick up and move the nanotubes to specific
      locations in the flat membrane, or the hybrid vesicle to specified regions on a
      surface. The ability to localize these hybrid vesicles on surfaces paves the way
      for creating nanoreactor arrays in fluidic devices. 

PMID- 23963615
TI  - Replacement of biologic by molecular techniques in diagnostic virology: thirty
      years after the advent of PCR technology-do we still need conventional methods?

PMID- 23963616
TI  - Therapeutic elastic tape reduces morbidity after wisdom teeth removal--a clinical
      trial.
AB  - OBJECTIVES: Although the extraction of an impacted third molar (3M) is a routine
      procedure, postoperative morbidities typically include swelling, pain, and
      trismus. The aim of the present study was to investigate whether the application
      of kinesiologic tape can improve the postoperative morbidities associated with 3M
      surgery, thereby improving the postoperative well-being of patients. MATERIALS
      AND METHODS: Forty patients assigned for prospective 3M removal were randomized
      into two treatment groups (with/without kinesiologic tape). Facial swelling was
      quantified using a five-line measurement at six specific time points. Pain scores
      were assessed using a visual analog scale, and mouth opening range was assessed
      by means of standard calipers. In addition, all patients were asked to evaluate
      overall satisfaction and swelling (both groups) and the effect of the tape on
      movement and comfort (taped group only). RESULTS: The postoperational application
      of kinesiologic tape reduced significantly all investigated parameters: swelling,
      pain, and trismus. Furthermore, patients with kinesiologic tape reported a
      significantly lower morbidity rate. CONCLUSION: The application of kinesiologic
      tape following a 3M surgery is a simple and economical, yet medically relevant
      approach. CLINICAL RELEVANCE: Kinesiologic tape offers patients a less traumatic
      postoperational experience and therefore holds promise to enhance the quality of
      life of a large cohort of the population.

PMID- 23963617
TI  - Effect of radical amplified photopolymerization (RAP) in resin-based composites.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of irradiation
      time and specimens thickness on the polymerization kinetic and variation in micro
      mechanical properties of two commercial resin-based composites (RBCs) based on
      radical amplified photopolymerization (RAP) technologyTM, and to compare them
      with four camphorquinone (CQ)/amine-based RBCs. MATERIALS AND METHODS: The
      materials were analysed by assessing the polymerization kinetic and the degree of
      cure (DC) at 0.1 mm and 2 mm depth during 5 minutes after photoinitiation, after
      curing for 10 s, 20 s and 40 s (Elipar Freelight2). The variation in micro
      mechanical properties (Vickers hardness (HV), indentation modulus (E), and depth
      of cure (DOC)) was assessed in 100 MUm steps on 6-mm-high specimens irradiated as
      above and stored in the water for 24 h at 37  degrees C. RESULTS: The results
      were statistically compared using one-way ANOVA with Tukey HSD post hoc test
      (alpha = 0.05) and a general linear model. The parameter material exerted the
      strongest effect on DC (partial eta-squared eta p (2) = 0.83), followed by
      irradiation time (eta p (2) = 0.27), and depth (eta p (2) = 0.09). The
      polymerization kinetic, well described by an exponential sum function, showed in
      all materials a faster decrease in carbon-carbon double bonds at 0.1 mm than at 2
      mm depth. The materials based on RAP achieved the highest DC values and a faster
      polymerization at both depths. The irradiation time exerted the strongest effect
      on the mechanical properties (DOC, eta p (2) = 0.96; HV, eta p (2) = 0.89; E, eta
      p (2) = 0.86), followed by depth (HV, eta p (2) = 0.63; E, eta p (2) = 0.54) and
      material (HV, eta p (2) = 0.40; E, eta p (2) = 0.67). At the most favorable
      curing conditions (40 s, surface), the mechanical properties of the analyzed
      materials varied between 11.38 (0.80) GPa in Estelite(r) Sigma Quick and 20.80
      (1.42) GPa in Estelite(r) Posterior for E, and between 74.33 (3.56) N/mm(2) in
      Tetric EvoCeram(r) and 120.71 (6.24) N/mm(2) in Estelite(r) Posterior for HV.
      CONCLUSIONS: RAP-initiated material demonstrated a higher increase in DOC with
      prolonged irradiation time than the analyzed CQ/amine based materials. CLINICAL
      RELEVANCE: An irradiation time of 20 s is also recommended for RAP-initiated
      RBCs.

PMID- 23963618
TI  - Retention forces of 14-unit zirconia telescopic prostheses with six double crowns
      made from zirconia--an in vitro study.
AB  - OBJECTIVES: The aim of this study was to evaluate the retention forces (RFs) of
      zirconia double-crown systems, with primary and secondary crowns made from
      zirconia in vitro. MATERIALS AND METHODS: Ten maxillary models with six abutment
      teeth were prepared. Sixty inner crowns were fabricated from pre-sintered
      zirconia with a taper of 0 degrees . Ten 14-unit telescopic prostheses (removable
      partial dentures, RDPs) were fabricated, using the same computer-aided
      design/computer-aided manufacturing system as that used for the inner crowns. The
      removal test was performed in a standardized setup using a universal testing
      device at a crosshead speed of 10 mm/min. Ten separation cycles were carried out
      for each single primary crown as well as for each 14-unit RDP in the presence of
      artificial saliva. The results were imported into a statistic program and
      analysed by a one-way ANOVA and post hoc tests. The level of significance was set
      at 5 %. RESULTS: The mean RFs of the single double-crown systems were in the
      range of 0.611-2.895 N, whereas the RFs for the whole RDP varied between 8.1 and
      13.6 N. RF was dependent on the abutment tooth (p < 0.001) and on the model (p <
      0.001). CONCLUSIONS: The results of this study indicate that the manufacturing of
      full-zirconia double-crown systems is possible as well as reproducible. The RFs
      are comparable to those reported from casted and electroformed double-crown
      systems. CLINICAL RELEVANCE: It has been shown that the RFs of the presented
      telescopic system are comparable to existing double-crown systems.

PMID- 23963619
TI  - Steps measured by pedometry and the relationship to adiposity in college women.
AB  - BACKGROUND: The aim of this study was to investigate the relationship between
      steps per day and adiposity among college women. METHODS: This study was cross
      sectional and included women ages 18-25. Participants wore a pedometer for 7
      consecutive days. Body composition was assessed using air-displacement
      plethysmography. Height, weight, and waist and hip circumferences were assessed.
      RESULTS: The women took 10,119 +/- 2836 steps per day. When divided into
      quartiles by steps, the top 2 quartiles of women in the study had significantly
      lower BMI, percent body fat, and waist and hip circumferences than the bottom
      quartile of women (P <= .05). Percent body fat was different between the bottom 2
      quartiles and the top 2 quartiles (P <= .05). The odds of having a body fat of
      greater than 32% were reduced by 21.9% for every increase of 1,000 steps taken
      per day (P <= .05). CONCLUSIONS: Steps per day are related to body composition in
      young adult women, but this relationship weakens with progressively higher step
      counts. A reasonable recommendation for steps in young adult women that is
      associated with the lowest BMIs and body fat seems to be between 10,000-12,000
      steps per day.

PMID- 23963620
TI  - Determining an anti-Mullerian hormone cutoff level to predict clinical pregnancy
      following in vitro fertilization in women with severely diminished ovarian
      reserve.
AB  - PURPOSE: Serum anti-Mullerian hormone (AMH) levels estimate ovarian reserve. The
      purpose of this study was to identify a minimum serum AMH level that correlates
      with acceptable clinical pregnancy rate (CPR) in women with severe diminished
      ovarian reserve (DOR) undergoing in vitro fertilization (IVF). METHODS(S): A
      historical cohort of severe DOR participants (age >=35) with day 3 FSH of >10
      ng/mL were included (n = 120). Participants were categorized into 3 groups: AMH
      <0.2 (Group 1, n = 38), AMH = 0.2-0.79 (Group 2, n = 57) and AMH >= 0.8 (Group 3,
      n = 25) ng/mL. The main outcome was CPR. The number of retrieved and mature
      oocytes, transferred embryos, spontaneous abortion (SAB) and live birth (LB)
      rates were also evaluated. RESULT(S): Among the three groups, there was no
      difference in day 3 FSH and estradiol, total gonadotropins dose used per cycle,
      or LB. Participants in Group 1 were two years older than those in Group 2 and had
      significantly higher BMI than those in Groups 2 and 3. The three groups
      significantly differed in AFC (Group 1< Group 2< Group 3; p = 0.001) and cycle
      cancellation rate (Group 1> Group 2> Group 3; p = 0.006), and had a trend toward
      significance in SAB rate (Group 1> Group 2> Group 3; p = 0.06). Group 3 had
      significantly more retrieved and mature oocytes than Groups 1 or 2. Group 2 and 3
      had significantly higher CPR per cycle start compared to Group 1. Although Group
      2 had significantly fewer oocytes retrieved and mature oocytes than Group 3, CPR
      per cycle start for both groups was not different. ROC curve indicated that the
      point of maximal inflection between lower and higher CPR represents an AMH value
      of 0.2 ng/mL. CONCLUSION(S): AMH of 0.2 ng/mL appears to be a meaningful
      threshold for predicting CPR in women with severe DOR at our practice. This
      information can be crucial during the pre-cycle counseling of these women.

PMID- 23963621
TI  - Volumetric imaging of erythrocytes using label-free multiphoton photoacoustic
      microscopy.
AB  - Photoacoustic microscopy (PAM) is an imaging modality well suited to mapping
      vasculature and other strong absorbers in tissue. However, one of the primary
      drawbacks to PAM when used for high-resolution imaging is the relatively poor
      axial resolution due to the inverse dependence on the transducer bandwidth. While
      submicron lateral resolution PAM can be achieved by tightly focusing the
      excitation light, the axial resolution is fundamentally limited to 10s of microns
      for typical transducer frequencies. Here we present a multiphoton PAM technique
      called transient absorption ultrasonic microscopy (TAUM), which results in a
      completely optically resolved voxel with an experimentally measured axial
      resolution of 1.5 microns. This technique is demonstrated by imaging individual
      red blood cells in three dimensions in blood smear and ex vivo tissues. To the
      best of our knowledge, this is the first demonstration of fully resolved,
      volumetric photoacoustic imaging of erythrocytes.

PMID- 23963622
TI  - The effect of glycation on arterial microstructure and mechanical response.
AB  - Like engineered materials, an artery's biomechanical behavior and function depend
      on its microstructure. Glycation is associated with both normal aging and
      diabetes and has been shown to increase arterial stiffness. In this study we
      examined the direct effect of glycation on the mechanical response of intact
      arteries and on the mechanical response and structure of elastin isolated from
      the arteries. Samples of intact arteries and isolated elastin were prepared from
      porcine aortas and glycated. The mechanical response of all samples was completed
      using a uniaxial material test system. Glycation levels were measured using
      ELISA. A confocal microscope was used to image differences in the structure of
      the glycated and untreated elastin fibers. We found that, under the conditions
      used in this study, glycation led to decreased stiffness of elastin isolated from
      arteries, which was associated with a thinning of elastin fibers as imaged by
      confocal microscopy. We observed no effect of glycation on collagen fibers under
      our treatment conditions. These results suggest that glycation leads to weakening
      of the elastin component of arteries that could contribute to vascular defects
      seen in diabetes and aging. Prevention of glycation reactions may be an important
      consideration for vascular health later in life.

PMID- 23963623
TI  - Akt suppression of TGFbeta signaling contributes to the maintenance of vascular
      identity in embryonic stem cell-derived endothelial cells.
AB  - The ability to generate and maintain stable in vitro cultures of mouse
      endothelial cells (ECs) has great potential for genetic dissection of the
      numerous pathologies involving vascular dysfunction as well as therapeutic
      applications. However, previous efforts at achieving sustained cultures of
      primary stable murine vascular cells have fallen short, and the cellular
      requirements for EC maintenance in vitro remain undefined. In this study, we have
      generated vascular ECs from mouse embryonic stem (ES) cells and show that active
      Akt is essential to their survival and propagation as homogeneous monolayers in
      vitro. These cells harbor the phenotypical, biochemical, and functional
      characteristics of ECs and expand throughout long-term cultures, while
      maintaining their angiogenic capacity. Moreover, Akt-transduced embryonic ECs
      form functional perfused vessels in vivo that anastomose with host blood vessels.
      We provide evidence for a novel function of Akt in stabilizing EC identity,
      whereby the activated form of the protein protects mouse ES cell-derived ECs from
      TGFbeta-mediated transdifferentiation by downregulating SMAD3. These findings
      identify a role for Akt in regulating the developmental potential of ES cell
      derived ECs and demonstrate that active Akt maintains endothelial identity in
      embryonic ECs by interfering with active TGFbeta-mediated processes that would
      ordinarily usher these cells to alternate fates.

PMID- 23963624
TI  - Research priorities for economic analyses of prevention: current issues and
      future directions.
AB  - In response to growing interest in economic analyses of prevention efforts, a
      diverse group of prevention researchers, economists, and policy analysts convened
      a scientific panel, on "Research Priorities in Economic Analysis of Prevention"
      at the 19th annual conference of the Society for Prevention Research. The panel
      articulated four priorities that, if followed in future research, would make
      economic analyses of prevention efforts easier to compare and more relevant to
      policymakers and community stakeholders. These priorities are: (1) increased
      standardization of evaluation methods, (2) improved economic valuation of common
      prevention outcomes, (3) expanded efforts to maximize evaluation generalizability
      and impact as well as (4) enhanced transparency and communicability of economic
      evaluations. In this paper, we define three types of economic analyses in
      prevention, provide context and rationale for these four priorities as well as
      related sub-priorities, and discuss the challenges inherent in meeting them. 

PMID- 23963625
TI  - Understanding "agency" in the translation of a health promotion program.
AB  - Health promotion interventions conducted under "ideal conditions" to prove their
      efficacy are often difficult to translate and disseminate for utilization in
      "real-world" settings. This article retrospectively integrates and analyzes the
      experience of three related projects. We investigate how the development and
      dissemination of a school-based nutrition and physical activity curriculum for
      American Indian elementary school children inspired the implementation of an
      across-the-lifespan train-the-trainer program that has trained more than 600
      trainers in American Indian communities nationwide. This process provides an
      opportunity to explore how individuals in the community and the context in which
      the research was conducted affected project outcomes in ways which were not
      anticipated. Results challenge the use of "internal validity" as the primary
      measure of success in translation-dissemination-utilization research. 

PMID- 23963626
TI  - Severe infantile Bordetella pertussis pneumonia in monozygotic twins with a
      congenital C3 deficiency.
AB  - Bordetella pertussis or whooping cough is a vaccine-preventable disease that
      still remains a serious infection in neonates and young infants. We describe two
      young infants, monozygotic twins, with a severe B. pertussis pneumonia of whom
      one needed extracorporeal membrane oxygenation. Diagnostic work-up of unexplained
      hematuria and proteinuria during the illness revealed low serum complement
      component 3 (C3) levels. During follow-up, C3 levels remained low (400-600 mg/L).
      Extensive analysis of the persistent low C3 levels revealed an unknown
      heterozygous mutation in the C3 gene in both siblings and their mother. This C3
      mutation in combination with the specific virulence mechanisms of B. pertussis
      probably contributed to the severe disease course in these cases. CONCLUSION: We
      propose that genetically caused complement disorders should be considered when
      confronted with severe cases of B. pertussis infection.

PMID- 23963627
TI  - Pentraxin 3 as a novel early biomarker for the prediction of Henoch-Schonlein
      purpura nephritis in children.
AB  - We investigated the potential role of pentraxin 3 (PTX3) in Henoch-Schonlein
      purpura (HSP), a common multisystemic vasculitis affecting children, as a
      predictor of Henoch-Schonlein purpura nephritis (HSPN). A total of 108 cases
      consisting of 34 children with HSP, 37 children with HSPN, and 37 healthy control
      children were enrolled in this prospective study from March 2010 to February
      2013. Blood and urine samples were collected to measure plasma PTX3, C-reactive
      protein (CRP), serum creatinine, blood urea nitrogen (BUN), urine microalbumin
      (MALB), and beta2-microglobulin (beta2-MG). Median plasma PTX3 concentrations
      were significantly higher in children with HSPN and HSP than in control subjects
      before treatment (6.99, 4.18-9.78 ng/ml; 3.19, 1.13-4.27 ng/ml; 1.24, 0.87-2.08
      ng/ml, respectively; all p < 0.05). Median plasma PTX3 concentrations were also
      significantly higher in children with HSPN than in children with HSP before
      treatment (6.99, 4.18-9.78 vs. 3.19, 1.13-4.27 ng/ml; p < 0.05). After treatment,
      median plasma PTX3 concentrations significantly decreased in children with HSP
      (from 3.19, 1.13-4.27 to 1.08, 0.65-2.19 ng/ml; p < 0.05) and HSPN (from 6.99,
      4.18-9.78 to 1.29, 1.01-2.26 ng/ml; p < 0.05). Plasma PTX3 concentration was
      positively correlated with CRP (rho = 0.532, p = 0.001), MALB (rho = 0.606, p <
      0.001), beta2-MG (rho = 0.490, p = 0.002), and 24-h urinary protein quantity (rho
      = 0.650, p < 0.001) in children with HSPN. Considering vasculitis, we found that
      PTX3 could be used as a more efficient potential predictor of HSPN than CRP as
      indicated by the area under the receiver operating characteristic (ROC) curve
      (AUCROC) of PTX3 (AUCROC = 0.837; p < 0.001) and CRP (AUCROC = 0.514; p = 0.845).
      The threshold PTX3 concentration with optimal sensitivity and specificity was
      4.30 ng/ml (sensitivity 73.0 %, specificity 79.6 %). CONCLUSION: PTX3 seems to
      have an important role in multisystemic vasculitis of HSP, may be involved in the
      development of HSPN, and used as an early biomarker to predict HSPN.

PMID- 23963628
TI  - Primary Carnitine deficiency in the Faroe Islands: health and cardiac status in
      76 adult patients diagnosed by screening.
AB  - BACKGROUND: Carnitine deficiency can cause cardiomyopathy and cardiac arrhythmia.
      The prevalence in the Faroe Islands is the highest reported in the world (1:300).
      A nationwide screening program identified 76 Faroese adult patients (15-80 years)
      with Primary Carnitine Deficiency (PCD). We describe prior and current health
      status and symptoms in these patients, especially focusing on cardiac
      characteristics. METHODS: Upon identification, patients were immediately admitted
      for physical examination, ECG, blood tests and initiation of L-carnitine
      supplementation. Medical records were reviewed and patients were interviewed.
      Echocardiography and blood tests were performed in 35 patients before and after L
      carnitine supplementation. RESULTS: All patients were either asymptomatic or had
      minor symptoms when diagnosed. Echocardiography including LVEF, global
      longitudinal strain and dimensions were normal apart from left ventricular
      hypertrophy with normal systolic function in one young male. Symptoms, e.g.
      fatigue, were reported in 43 % with a reduction to 12 % (p < 0.01) following
      initiation of L-carnitine supplementation. Eighty two % reported participation in
      sports of which 52 % were on a competitive level. ECGs showed limited changes and
      blood tests were normal. Mean plasma free carnitine increased from 6.1 MUmol/L to
      15.1 MUmol/L (p < 0.01) within 50 days of L-carnitine supplementation.
      CONCLUSION: PCD in adults can cause serious symptoms, but adult Faroese patients
      identified through a screening program were predominantly asymptomatic with a
      normal cardiac structure and function.

PMID- 23963629
TI  - Psychopharmacology for medically ill adolescents.
AB  - Medically ill adolescents are at increased risk for psychological distress and/or
      functional impairment. However, there are few research studies examining the
      optimal psychiatric treatments for this population. Psychiatric medication
      recommendations are largely based on studies of youth with a primary psychiatric
      disorder, adult studies, hypothesized mechanisms of action, and/or clinical
      experience. This paper provides evidence-informed recommendations for the
      psychopharmacological treatment of acutely medically ill adolescents suffering
      from significant psychological distress and/or functional impairment.
      Representing the most common problems among medically ill adolescents that are
      treated with psychiatric medications, recommendations are provided for anxiety
      and depression; iatrogenic medical trauma, inadequate sleep and insomnia; and,
      delirium. 

PMID- 23963630
TI  - Altered brain reward circuits in eating disorders: chicken or egg?
AB  - The eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) are severe
      psychiatric disorders with high mortality. Our knowledge about the neurobiology
      of eating disorders is very limited, and the question remains whether alterations
      in brain structure or function in eating disorders are state related, remnants of
      the illness or premorbid traits. The brain reward system is a relatively well
      characterized brain circuitry that plays a central role in the drive to eat and
      individuals with current or past eating disorders showed alterations in those
      pathways compared to controls. Here we propose that structural and functional
      alterations in the insula and frontal cortex, including orbitofrontal and
      cingulate regions, areas that contribute to reward and anxiety processing, could
      predispose to developing an eating disorder and that adaptive changes in those
      circuits in response to malnutrition or repeated binge eating and purging could
      further promote illness behavior, hinder recovery and contribute to relapse. 

PMID- 23963631
TI  - Psychiatric aspects of bariatric surgery.
AB  - While most conventional treatments for individuals with severe obesity have a
      modest and short lived impact bariatric surgery has been consistently shown to
      result in long-term marked weight loss and significant improvement in medical
      comorbidities. Empirical data suggest a high prevalence of mental disorders among
      bariatric surgery candidates. This article reviews specific areas of
      psychopathology, problems in using psychopharmacological medications post
      surgery, body contouring, and recommendations for pre and post-surgery care.
      Available research indicates a decrease in psychiatric symptoms post-surgery.
      However, in some patients the improvement appears to erode over time. Therefore,
      bariatric surgery patients should be monitored not only before surgery but also
      following surgery and referred for mental health treatment if problems develop. 

PMID- 23963632
TI  - Notch signaling in skeletal stem cells.
AB  - The skeleton originates from stem cells residing in the sclerotome and neural
      crest that undergo proliferation, migration, and commitment. The development of
      the skeletal stem cells is influenced by many signaling pathways that govern cell
      fate determination, proliferation, differentiation, and apoptosis. This review
      will focus on Notch signaling functions in regulating the different cell types
      that form the skeletal system as well as the interplay between them to maintain
      homeostasis. Osteochondroprogenitors require Notch signaling to maintain
      multipotency and to prevent premature differentiation into osteoblasts.
      Subsequently, overactivation of Notch signaling suppresses osteoblast maturation.
      Moreover, Notch signaling in osteochondroprogenitors is required for chondrocyte
      proliferation and hypertrophy and suppresses terminal differentiation.
      Translational studies demonstrated a crucial role of Notch signaling in
      osteosarcoma and osteoarthritis, where concepts derived from developmental
      pathways are often recapitulated. This brings hope of taking advantage of the
      molecular mechanisms learned from development to approach the pathological
      processes underlying abnormal bone/cartilage metabolism or tumorigenesis.
      Pharmacological agents that target Notch receptors or ligands in a tissue
      specific fashion would offer new opportunities for treating bone/cartilage
      diseases caused by dysregulation of Notch signaling. 

PMID- 23963633
TI  - Once-Weekly Injection of Low-Dose Teriparatide (28.2 MUg) Reduced the Risk of
      Vertebral Fracture in Patients with Primary Osteoporosis.
AB  - We conducted a randomized, double-blind trial to assess the effect of 28.2 MUg
      teriparatide versus placebo (1.4 MUg teriparatide) on reduction of the incidence
      of vertebral fractures. Individuals enrolled in this study included patients with
      primary osteoporosis with one to five vertebral fractures and capable of self
      supported walking. Attention was focused on incident vertebral fractures, change
      in bone mineral density (BMD) of the lumbar spine, and safety. A total of 316
      subjects participated in the study, which lasted up to 131 weeks. Incident
      vertebral fractures occurred in 3.3% of subjects in the 28.2 MUg teriparatide
      treated group and 12.6% of subjects in the placebo group during the 78-weeks
      study period. Kaplan-Meier estimates of risk after 78 weeks were 7.5 and 22.2 %
      in the teriparatide and placebo groups, respectively, with a relative risk
      reduction of 66.4% by teriparatide (P = 0.008). Lumbar BMD in the 28.2 MUg
      teriparatide group increased significantly by 4.4 +/- 4.7 % at 78 weeks, which
      was significantly higher than the corresponding data in the placebo group (P =
      0.001). Adverse events were observed in 86.7% of individuals in the teriparatide
      group and 86.1% of those in the placebo group. In conclusion, weekly injection of
      a low-dose of teriparatide (28.2 MUg) reduced the risk of incident vertebral
      fractures and increased lumbar BMD.

PMID- 23963634
TI  - Other than daytime working is associated with lower bone mineral density: the
      Korea National Health and Nutrition Examination Survey 2009.
AB  - Occupation affects bone mineral density (BMD); however, only few studies have
      been published. This study evaluated the effect of working time during a day on
      BMD. The cross-sectional study involved 18- to 50-year-old people who reported
      their working time and were measured for BMD using dual-energy X-ray
      absorptiometry in the Fourth Korea National Health and Nutrition Examination
      Survey 2009. The time period of work was divided into "daytime" and "other than
      daytime." The other-than-daytime group included evening time, nighttime, regular
      shift time, and irregular shift time. Among 3,005 subjects, 2,378 were daytime
      workers and 627 were other-than-daytime workers. The mean BMD of the total femur
      and lumbar spine were significantly lower in other-than-daytime workers compared
      to daytime workers (femur 0.948 vs. 0.966 g/cm2, respectively, p = 0.001; lumbar
      spine 0.976 vs. 0.988 g/cm2, respectively, p = 0.023). The other-than-daytime
      group had lower levels of serum 25-hydroxyvitamin D than the daytime group (16.3
      vs. 17.6 ng/mL, p < 0.001). The proportion of osteopenia (T score < -1.0) was
      higher in the other-than-daytime than the daytime group (34.3 vs. 29.1 %, p =
      0.014). After adjustment for age, sex, socioeconomic status, lifestyle factors,
      daily intake of calcium, and vitamin D level, the relative risks of osteopenia of
      regular-shift and irregular-shift workers were significantly higher (1.65, 95 %
      CI 1.05-2.60; 1.78, 95 % CI 1.09-2.89) than those of daytime workers. These data
      suggest that other-than-daytime working, especially regular and irregular shift
      working, is associated with decreased BMD and increased risk for osteopenia in
      Korean adults.

PMID- 23963635
TI  - Efficacy of reversal of aortic calcification by chelating agents.
AB  - Elastin-specific medial vascular calcification, termed "Monckeberg's sclerosis,"
      has been recognized as a major risk factor for various cardiovascular events. We
      hypothesize that chelating agents, such as disodium ethylenediaminetetraacetic
      acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), and sodium thiosulfate
      (STS) might reverse elastin calcification by directly removing calcium from
      calcified tissues into soluble calcium complexes. We assessed the chelating
      ability of EDTA, DTPA, and STS on removal of calcium from hydroxyapatite (HA)
      powder, calcified porcine aortic elastin, and calcified human aorta in vitro. We
      show that both EDTA and DTPA could effectively remove calcium from HA and
      calcified tissues, while STS was not effective. The tissue architecture was not
      altered during chelation. In the animal model of aortic elastin-specific
      calcification, we further show that local periadventitial delivery of EDTA loaded
      in to poly(lactic-co-glycolic acid) nanoparticles regressed elastin-specific
      calcification in the aorta. Collectively, the data indicate that elastin-specific
      medial vascular calcification could be reversed by chelating agents. 

PMID- 23963636
TI  - Effects of Home-Based Walking on Quality of Life and Fatigue Outcomes in Early
      Stage Breast Cancer Survivors: A 12-Week Pilot Study.
AB  - BACKGROUND: Adjuvant treatment for breast cancer may result in long-lasting,
      adverse emotional and physical side effects, and reduce quality of life (QOL).
      This pilot study examined the effects of a home-based walking program on QOL and
      fatigue in early stage breast cancer survivors and whether changes in walking
      behavior were associated with changes in outcomes. METHODS: Participants (n = 32)
      were randomized to a 12-week home-based walking intervention plus brief telephone
      counseling (n = 20) or a wait-list control group (n = 12). Self-reported fatigue,
      QOL, and walking were assessed at baseline and 12-weeks. Results are presented as
      effect sizes. RESULTS: Participants in the intervention had improvements in a
      majority of fatigue and QOL outcomes, whereas the control group had no change or
      worsened in many; effect sizes were generally in the small to medium range.
      Changes in fatigue/QOL outcomes were associated with changes in walking behavior,
      with effects generally in the small to medium range. CONCLUSION: Home-based
      physical activity (walking) programs may be an appropriate avenue for alleviating
      the adverse side effects that often accompany adjuvant treatment for breast
      cancer. These programs have potential for widespread dissemination, which may
      have considerable impact on the quality of life of women recently completing
      breast cancer treatment.

PMID- 23963637
TI  - Development of longitudinal smooth muscle in the posterior mesenteric artery and
      purinergic regulation of its contractile responses in chickens.
AB  - This study was designed to clarify development and the neural regulation of
      longitudinal smooth muscle in the chicken posterior mesenteric artery to generate
      new hypotheses for the roles of arterial longitudinal muscles. The existence of
      longitudinal muscles was examined with hematoxylin-eosin staining. A well
      developed longitudinal muscle layer exists in the posterior mesenteric artery of
      adult female chickens but not adult male chickens. The muscle layer is poorly
      developed in chickens aged < 15 weeks, even in female chickens. Mechanical
      responses of muscles were recorded and perivascular nerves were stimulated by
      electrical field stimulation (EFS). EFS induced monophasic contractions in
      longitudinal muscle of the posterior mesenteric artery segment, and those
      responses were inhibited by pretreatment with tetrodotoxin. Blockers for
      cholinoceptors and adrenoceptors did not affect EFS-evoked contractions but an
      antagonist for P2X purinoceptors blocked them. The present study demonstrated
      that the longitudinal muscle in the posterior mesenteric artery of the domestic
      fowl develops between the 5th and 15th week of life, suggesting that its
      development is involved in oviposition. The longitudinal muscle might have a role
      in resisting extensional stress from the oviduct containing eggs. Moreover, the
      arterial longitudinal muscle is regulated by purinergic neurons via P2X
      purinoceptors. 

PMID- 23963638
TI  - Sox transcription factors require selective interactions with Oct4 and specific
      transactivation functions to mediate reprogramming.
AB  - The unique ability of Sox2 to cooperate with Oct4 at selective binding sites in
      the genome is critical for reprogramming somatic cells into induced pluripotent
      stem cells (iPSCs). We have recently demonstrated that Sox17 can be converted
      into a reprogramming factor by alteration of a single amino acid (Sox17EK) within
      its DNA binding HMG domain. Here we expanded this study by introducing analogous
      mutations to 10 other Sox proteins and interrogated the role of N-and C-termini
      on the reprogramming efficiency. We found that point-mutated Sox7 and Sox17 can
      convert human and mouse fibroblasts into iPSCs, but Sox4, Sox5, Sox6, Sox8, Sox9,
      Sox11, Sox12, Sox13, and Sox18 cannot. Next we studied regions outside the HMG
      domain and found that the C-terminal transactivation domain of Sox17 and Sox7
      enhances the potency of Sox2 in iPSC assays and confers weak reprogramming
      potential to the otherwise inactive Sox4EK and Sox18EK proteins. These results
      suggest that the glutamate (E) to lysine (K) mutation in the HMG domain is
      necessary but insufficient to swap the function of Sox factors. Moreover, the HMG
      domain alone fused to the VP16 transactivation domain is able to induce
      reprogramming, albeit at low efficiency. By molecular dissection of the C
      terminus of Sox17, we found that the beta-catenin interaction region contributes
      to the enhanced reprogramming efficiency of Sox17EK. To mechanistically
      understand the enhanced reprogramming potential of Sox17EK, we analyzed ChIP
      sequencing and expression data and identified a subset of candidate genes
      specifically regulated by Sox17EK and not by Sox2.

PMID- 23963639
TI  - Nickel-catalyzed chemo- and stereoselective alkenylative cyclization of 1,6
      enynes with alkenyl boronic acids.
AB  - Discover nickel! A nickel-catalyzed alkenylative cyclization of 1,6-enynes and
      alkenyl boronic acids affording substituted pyrrolidines and dihydrofurans is
      described (see scheme; cod = 1,5-cyclooctadiene, Ts = p-toluene sulfonate). The
      reaction is highly chemo- and stereoselective. A possible reaction mechanism
      involving a nickelacyclopentene intermediate is proposed.

PMID- 23963640
TI  - Molecular identification and phylogenetic analysis of Heterakis gallinae from
      native chickens in Egypt.
AB  - The genomic DNA was extracted from nematode parasites, Heterakis gallinae from
      specific host, native chickens. The polymerase chain reaction (PCR) was applied
      to make amplification of the DNA content that aids in the further studies. The
      primer was used in the PCR reactions that have the following sequences: forward
      (5'-GTTTCCGTAGGTGAACCTGC-3') and reverse (5'-ATATGCTTAAGTTCAGCGGGT-3'). It gave
      total amplified fragment markers at 914 bp. The gene sequences obtained from
      Egyptian H. gallinae was to make phylogenetic relationships of Egyptian H.
      gallinae with other nematodes on the database of an accession number (AJ876757),
      showing that it was nearly similar to Heterakis gallinarum.

PMID- 23963641
TI  - Slab-selective, BOLD-corrected VASO at 7 Tesla provides measures of cerebral
      blood volume reactivity with high signal-to-noise ratio.
AB  - PURPOSE: MRI methods sensitive to functional changes in cerebral blood volume
      (CBV) may map neural activity with better spatial specificity than standard
      functional MRI (fMRI) methods based on blood oxygen level dependent (BOLD)
      effect. The purpose of this study was to develop and investigate a vascular space
      occupancy (VASO) method with high sensitivity to CBV changes for use in human
      brain at 7 Tesla (T). METHODS: To apply 7T VASO, several high-field-specific
      obstacles must be overcome, e.g., low contrast-to-noise ratio (CNR) due to
      convergence of blood and tissue T1 , increased functional BOLD signal change
      contamination, and radiofrequency field inhomogeneities. In the present method,
      CNR was increased by keeping stationary tissue magnetization in a steady-state
      different from flowing blood, using slice-selective saturation pulses.
      Interleaved acquisition of BOLD and VASO signals allowed correction for BOLD
      contamination. RESULTS: During visual stimulation, a relative CBV change of 28%
      +/- 5% was measured, confined to gray matter in the occipital lobe with high
      sensitivity. CONCLUSION: By carefully considering all the challenges of high
      field VASO and filling behavior of the relevant vasculature, the proposed method
      can detect and quantify CBV changes with high CNR in human brain at 7T.

PMID- 23963642
TI  - The POSH/JIP-1 scaffold network regulates TCR-mediated JNK1 signals and effector
      function in CD8(+) T cells.
AB  - Signals from the T-cell recognition of antigen program effector functions are
      necessary to clear infections and tumors. The JNK pathway is critically important
      in regulating this process. In T lymphocytes, JNK1 and JNK2 have distinct
      functions depending on their maturation state and cell-type. However, the
      mechanisms that regulate their isoform-specific activity and function are still
      unclear. Here, we identify plenty of SH3 (POSH) and JNK-interacting protein 1
      (JIP-1) as a multiprotein scaffold network for TCR-mediated JNK1 activation in
      CD8(+) T cells. Disruption of the POSH/JIP-1 complex led to profound defects in
      the activation of JNK1, as well as deficient activation or induction of the
      transcription factors c-Jun, T-bet, and Eomesodermin. Furthermore, disruption of
      the POSH/JIP complex in CD8(+) T cells resulted in impaired proliferation,
      decreased cytokine expression, and the inability to control tumors. Collectively,
      these data identify a mechanism for the specific regulation of TCR-dependent JNK1
      activation and function that is key for CD8(+) T-cell responses. 

PMID- 23963643
TI  - Parent-child hostility and child and adolescent depression symptoms: the
      direction of effects, role of genetic factors and gender.
AB  - Identifying environmental risk factors in the pathway to depression is an
      important research goal. To extend prior research, designs that rule out
      alternative explanatory factors; genetic effects and reverse causation, and
      permit tests of both parent and child gender are required. The present study used
      two different samples to address these issues. A longitudinal community sample of
      316 families (157 boys, 159 girls) aged 11-12 years (mean 11.7) at Time 1 and 12
      13 years at Time 2 (mean 12.7) was used to test the direction of effects between
      parent hostility and child and adolescent depression symptoms. A genetically
      sensitive sample of 1,075 twin pairs; 653 dizygotic (135 male, 183 female, 335
      opposite sex) and 422 monozygotic (180 male and 242 female) aged 12-20 years
      (mean 16.12) was used to test whether parent hostility had environmental effects.
      Analyses were conducted separately by parent and child gender. Using cross-lagged
      panel analyses, the association between mother-daughter hostility and depression
      symptoms was found to be longitudinal and bidirectional with reciprocal effects
      between mothers and daughters. Behavioural genetic analyses in the twin sample
      revealed a significant environmental link between mother hostility and symptoms
      of daughter depression independent of genetic factors. A significant pathway was
      found between daughter depressive symptoms and father hostility but not vice
      versa. This association was accounted for by genetic factors in behavioural
      genetic analyses. Findings provide evidence of an environmental risk pathway to
      depression symptoms and identify patterns of variation according to parent and
      child gender. Results are discussed in relation to underlying explanatory
      processes and clinical implications. 

PMID- 23963644
TI  - Comparison of clinical characteristics of bipolar and depressive disorders in
      Korean clinical sample of youth: a retrospective chart review.
AB  - The purpose of this study was to compare the clinical characteristics of bipolar
      disorder I, II (BD I and II) and not otherwise specified (BD NOS) to those of
      major depressive disorder (MDD) in a clinical sample of Korean children and
      adolescents. This study was a cross-sectional review of longitudinal
      observational data. Two psychiatrists retrospectively reviewed the medical
      records of 198 children and adolescents (age 6-18) that were diagnosed as having
      bipolar or depressive disorders from March 2010 to February 2012 at Department of
      Psychiatry of Asan Medical Center, Seoul, Korea. Every subject's diagnoses were
      reviewed and confirmed. BD I, II and MDD were assessed according to the
      Diagnostic and Statistical Manual-IV criteria. BD NOS was defined based on the
      criteria for the Course and Outcome of Bipolar Youth study. Comparisons were made
      in demographic information, clinical characteristics, family history, and
      psychiatric comorbidities at baseline and during observation. Among 198 subjects,
      20 (10.1 %) subjects were diagnosed as having BD I, 10 (5.1 %) as BD II, 25 (12.6
      %) as BD NOS and 143 (73.7 %) as MDD. BD depression was associated with mood
      change while taking an antidepressant, familial bipolarity, aggressive behaviors,
      and atypical features. Comorbid obsessive-compulsive disorder tended to be higher
      in BD NOS than in MDD. Presence of psychosocial stressors was more common in MDD
      than in BD depression. In children and adolescents, bipolar depression is
      distinct from unipolar depression in family history, comorbidity, and clinical
      characteristics. 

PMID- 23963645
TI  - Effect of the hydration on the biomechanical properties in a fibrin-agarose
      tissue-like model.
AB  - The effect of hydration on the biomechanical properties of fibrin and fibrin
      agarose (FA) tissue-like hydrogels is reported. Native hydrogels with
      approximately 99.5% of water content and hydrogels with water content reduced
      until 90% and 80% by means of plastic compression (nanostructuration) were
      generated. The biomechanical properties of the hydrogels were investigated by
      tensile, compressive, and shear tests. Experimental results indicate that
      nanostructuration enhances the biomechanical properties of the hydrogels. This
      improvement is due to the partial draining of the water that fills the porous
      network of fibers that the plastic compression generates, which produces a denser
      material, as confirmed by scanning electron microscopy. Results also indicate
      that the characteristic compressive and shear parameters increase with agarose
      concentration, very likely due to the high water holding capacity of agarose,
      which reduces the compressibility and gives consistency to the hydrogels.
      However, results of tensile tests indicate a weakening of the hydrogels as
      agarose concentration increases, which evidences the anisotropic nature of these
      biomaterials. Interestingly, we found that by adjusting the water and agarose
      contents it is possible to tune the biomechanical properties of FA hydrogels for
      a broad range, within which the properties of many native tissues fall.

PMID- 23963646
TI  - Low density receptor-related protein 1 (LRP1) promotes anti-inflammatory
      phenotype in murine macrophages.
AB  - We have previously reported that apolipoprotein E (apoE), a protein component of
      very-low-density lipoproteins (VLDL) and high-density lipoproteins and a potent
      plasma-borne atheroprotective factor, exerts anti-inflammatory activity in
      macrophages by switching the activation profile from M1 ("classic") to M2
      ("alternative") in a process involving signaling via low-density lipoprotein
      receptor (LDLR) family members including the VLDL receptor (VLDLR) or apoE
      receptor-2 (apoER2). The present study was undertaken to investigate whether LDLR
      related protein 1 (LRP-1), another member of the LDLR family and a ubiquitously
      expressed multifunctional cell surface receptor, modulates M1->M2 conversion in
      murine macrophages. We investigate bone marrow or peritoneal macrophages isolated
      from wild-type C57/Bl6 mice or mice with conditional inactivation of the LRP-1
      gene in the myeloid lineage for the expression of polarization markers. Our
      results suggest that the deficiency of LRP-1 down-regulates M2 marker expression
      in macrophages, while enhancing the macrophage response to M1 stimuli. To our
      knowledge, this is the first demonstration that LRP-1 affects macrophage
      polarization and promotes the development of an anti-inflammatory M2 functional
      phenotype. 

PMID- 23963648
TI  - Tenascin-C is expressed by human glioma in vivo and shows a strong association
      with tumor blood vessels.
AB  - The extracellular matrix (ECM) protein tenascin-C (TN-C) is upregulated within
      glioma tissues and cultured glioma cell lines. TN-C possesses a multi-modular
      structure and a variety of functional properties have been reported for its
      domains. We describe five novel monoclonal antibodies identifying different
      domains of TN-C. The epitopes for these antibodies were investigated by using
      recombinantly expressed fibronectin type III domains of TN-C. The biological
      effects of TN-C fragments on glioma cell proliferation and adhesion were
      analyzed. The expression pattern of TN-C in human glioma tissue sections and in
      glioma cell lines was studied with the novel library of monoclonal antibodies.
      The immunocytochemical analyses of the established human glioma cell lines U-251
      MG, U-373-MG and U-87-MG revealed distinct staining patterns for each antibody.
      Robust expression of TN-C was found within the tumor mass of surgery specimens
      from glioblastoma. In many cases, the expression of this ECM molecule was clearly
      associated with blood vessels, particularly with microvessels. Three of the new
      antibodies highlighted individual TN-C-expressing single cells in glioma tissues.
      The effect of TN-C domains on glioma cells was examined by a BrdU-proliferation
      assay and an adhesion assay. Short fragments of constitutively expressed TN-C
      domains did not exert significant effects on the proliferation of glioma cells,
      whereas the intact molecule increased cell division rates. In contrast, the long
      fragment TNfnALL containing all of the FNIII domains of TN-C decreased
      proliferation. Additionally, we found strong differences between the adhesion
      influencing properties of the recombinant fragments on glioma cells. 

PMID- 23963647
TI  - Glucocorticoid receptor antagonist and siRNA prevent senescence of human bone
      marrow mesenchymal stromal cells in vitro.
AB  - We investigate the effects mediated by glucocorticoid (GC) receptor (GR) blockage
      by using RU486, a GR antagonist and GR short interfering RNA (GR siRNA) on the
      proliferative and differentiation capabilities of human bone marrow mesenchymal
      stromal/stem cells (MSCs) and on their senescence and antioxidant levels during
      extended in vitro culture. Treatment with either RU486 or GR siRNA for a 7-day
      period significantly increased the proliferation of MSCs and their osteogenic
      capabilities, as reflected by an increase in alkaline phosphatase (ALP) levels
      after differentiation. Following 4 weeks of treatment, MSCs improved or
      maintained their proliferation rates, whereas control MSCs exhibited decreased
      proliferation. Although all MSCs exhibited reduced osteogenic potential after 4
      weeks of in vitro culture, the MSCs treated with GR inhibitors showed higher ALP
      levels than untreated MSCs on being subjected to osteogenic differentiation. Such
      treatment also significantly down-regulated the adipogenic capabilities of MSCs.
      Telomere lengths and the activities of telomerase and superoxide dismutase of
      MSCs treated with either RU486 or GR siRNA appeared to be higher than those
      detected in controls. These results demonstrate that the blockage of effects
      mediated by the GCs normally found in fetal bovine serum might postpone
      senescence of these cells by up-regulating their antioxidant levels. Our data
      suggest that the blocking of the effects mediated by GCs might extend the
      lifespan of endogenous MSCs in patients who have elevated GC levels as a
      consequence of advancing age or estrogen depletion.

PMID- 23963649
TI  - Effect of N-ethylmaleimide, chymotrypsin, and H2O2 on the viscoelasticity of
      human erythrocytes: experimental measurement and theoretical analysis.
AB  - The physiological functions of erythrocytes depend critically on their
      morphology, deformability, and aggregation capability in response to external
      physical and chemical stimuli. The dynamic deformability can be described in
      terms of their viscoelasticity. We applied jumping optical tweezers to trap and
      stretch individual red blood cells (RBCs) to characterize its viscoelasticity in
      terms of the Young's modulus and viscosity by analyzing the experimental data of
      dynamic deformation using a 2-parameter Kelvin solid model. The effects of three
      chemical agents (N -ethylmaleimide, Chymotrypsin, and Hydrogen peroxide) on RBC's
      mechanical properties were studied by comparing the Young's modulus and viscosity
      of RBCs with and without these chemical treatments. Although the effects of each
      of these chemicals on the molecular structures of RBC may not be exclusive, based
      on the dominant effect of each chemical, we attempted to dissect the main
      contributions of different constituents of the RBC membrane to its viscosity and
      elasticity.

PMID- 23963650
TI  - Development and validation of a new self-report instrument for measuring
      sedentary behaviors and light-intensity physical activity in adults.
AB  - BACKGROUND: Low levels of physical activity and high levels of sedentary behavior
      (SB) are major public health concerns. This study was designed to develop and
      validate the 7-day Sedentary (S) and Light Intensity Physical Activity (LIPA) Log
      (7-day SLIPA Log), a self-report measure of specific daily behaviors. METHOD: To
      develop the log, 62 specific SB and LIPA behaviors were chosen from the
      Compendium of Physical Activities. Face-to-face interviews were conducted with 32
      sedentary volunteers to identify domains and behaviors of SB and LIPA. To
      validate the log, a further 22 sedentary adults were recruited to wear the GT3x
      for 7 consecutive days and nights. RESULTS: Pearson correlations (r) between the
      7-day SLIPA Log and GT3x were significant for sedentary (r = .86, P < .001), for
      LIPA (r = .80, P < .001). Lying and sitting postures were positively correlated
      with GT3x output (r = .60 and r = .64, P < .001, respectively). No significant
      correlation was found for standing posture (r = .14, P = .53).The kappa values
      between the 7-day SLIPA Log and GT3x variables ranged from 0.09 to 0.61,
      indicating poor to good agreement. CONCLUSION: The 7-day SLIPA Log is a valid
      self-report measure of SB and LIPA in specific behavioral domains.

PMID- 23963651
TI  - Sleep-disordered breathing in patients undergoing transfemoral aortic valve
      implantation for severe aortic stenosis.
AB  - BACKGROUND: We examined the prevalence of sleep-disordered breathing (SDB) in
      patients with severe aortic valve stenosis (AS) and the impact of transfemoral
      aortic valve implantation (TAVI) on SDB. METHODS: 79 patients underwent
      cardiorespiratory polygraphy (PG) before TAVI (CoreValveTM), 62 of them a second
      PG after the procedure. RESULTS: Forty-nine (62 %) patients had obstructive sleep
      apnea (OSA), 25 (32 %) central sleep apnea (CSA), and 5 (6 %) presented without
      significant SDB (apnea-hypopnea index (AHI) < 5/h). Among the 62 patients
      evaluated before and after TAVI, 36 (58 %) had OSA, 22 (36 %) CSA, and 4 patients
      (7 %) no SDB. AHI was significantly higher in CSA patients than in OSA patients
      (34.5 +/- 18.3 vs. 18.0 +/- 12.6/h, p < 0.001). Successful TAVI had a significant
      impact on CSA but not on OSA: CSA patients with optimal TAVI results experienced
      a significant reduction in central respiratory events (AHI 39.6 +/- 19.6-23.1 +/-
      16.0/h, p = 0.035), while no changes were detected in OSA patients (AHI 18.8 +/-
      13.0-20.25 +/- 13.4/h, p = 0.376). In contrast, in patients who developed at
      least moderate periprosthetic aortic regurgitation (AR > I), CSA increased
      significantly (AHI 26.3 +/- 13.2-39.2 +/- 18.4/h, p = 0.036), whereas no acute
      change was seen in patients with OSA (AHI 10.5 +/- 7.8-12.5 +/- 5.0/h, p = 0.5).
      CONCLUSION: OSA and CSA are prevalent in more than 90 % of patients undergoing
      TAVI for severe aortic valve stenosis. Successful TAVI had no significant impact
      on OSA but improved CSA. In case of an acute change from pressure overload
      (aortic stenosis) to acute volume overload (aortic regurgitation after TAVI),
      central, but not obstructive, sleep apnea deteriorated.

PMID- 23963652
TI  - Vitamin C enhances Nanog expression via activation of the JAK/STAT signaling
      pathway.
AB  - Vitamin C (Vc), also known as ascorbic acid, is involved in many important
      metabolic and physiological reactions in the body. Here, we report that Vc
      enhances the expression of Nanog and inhibits retinoic acid-induced
      differentiation of embryonic stem cells. We investigated Vc regulation of Nanog
      through Janus kinase/signal transducer and activator of transcription pathway
      using cell signaling pathway profiling systems, and further confirmed by specific
      pathway inhibition. Using overexpression and knockdown strategies, we
      demonstrated that STAT2 is a new positive regulator of Nanog and is activated by
      phosphorylation following Vc treatment. In addition, site mutation analysis
      identified that STAT2 physically occupies the Nanog promoter, which was confirmed
      by chromatin immunoprecipitation and electrophoretic mobility shift assays. Taken
      together, our data suggest a role for Vc in Nanog regulation networks and reveal
      a novel role for STAT2 in regulating Nanog expression.

PMID- 23963653
TI  - Nurses in distress? An explorative study into the relation between distress and
      individual neuropsychiatric symptoms of people with dementia in nursing homes.
AB  - OBJECTIVES: To optimize care and interventions to improve care, and to reduce
      staff burden, it is important to have knowledge of the relation between
      individual neuropsychiatric symptoms and distress of care staff. We therefore
      explored the relation between frequency and severity of individual
      neuropsychiatric symptoms and distress of care staff. DESIGN: This is an
      explorative study with a cross-sectional design. PARTICIPANTS AND SETTING: Care
      staff was interviewed regarding 432 residents of 17 nursing homes for people with
      dementia. MEASUREMENTS: Behavioural problems were assessed using the Nursing Home
      version of the Neuropsychiatric Inventory (NPI-NH) questionnaire. The distress
      scale of the NPI-NH was used to determine the distress of care staff. RESULTS:
      Agitation/aggression had the highest mean distress score and was also the most
      prevalent symptom. Disinhibition and irritability/lability also had high mean
      distress scores, whereas euphoria/elation, hallucinations and apathy had the
      lowest mean distress score. The symptom severity of each symptom strongly
      predicted the distress score, whereas the frequency of the symptoms was a less
      important factor. CONCLUSIONS: Although some of these findings are in accordance
      with studies among informal caregivers, there are also notable differences.
      Apathy caused little distress among care staff. Therefore, care staff might not
      feel the urgency to explore the causes of this symptom. The findings of this
      study emphasize the importance of supporting care staff in the management of
      behavioural problems, especially aggression and apathy.

PMID- 23963654
TI  - Ophthalmologic screening in 25 consecutive geriatric psychiatric inpatient
      admissions.
AB  - In the aging process, people are at increasing risk of visual abnormalities such
      as cataracts, glaucoma, age-related macular degeneration, and other retinal
      defects. This holds true for geriatric psychiatric patients as well. These
      ophthalmic problems may increase risk of falls or increase the comorbidity from
      dementing processes and depression. Geriatric patients presenting for psychiatric
      treatment may also be misdiagnosed or under-diagnosed as a result of these visual
      problems. This quality assurance review of 25 consecutive geriatric psychiatric
      inpatients demonstrated discrepancies between chart documentation and actual
      ophthalmologic pathology present in the patients. Doing a simple but complete
      ophthalmologic screening as part of the general physical examination on admission
      to an inpatient psychiatric unit can identify those patients who will need more
      in depth examination of their eyes and promote more accurate differential
      diagnoses for the patients. 

PMID- 23963657
TI  - Subpial transection surgery for epilepsy.
AB  - BACKGROUND: Nearly 30% of patients with epilepsy continue to have seizures in
      spite of several antiepileptic drug (AED) regimens. In such cases they are
      regarded as having refractory, or uncontrolled epilepsy.There is no universally
      accepted definition for uncontrolled or medically refractory epilepsy, but for
      the purpose of this review, we will consider seizures to be drug resistant if
      they failed to respond to a minimum of two AEDs. It is believed that early
      surgical intervention may prevent seizures at a younger age and improve the
      intellectual and social status of children. There are many types of surgery for
      refractory epilepsy with subpial transection being one. OBJECTIVES: Our main aim
      is to determine the benefits and adverse effects of subpial transection for
      partial-onset seizures and generalised tonic-clonic seizures in children and
      adults. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialised
      Register (8 August 2013), The Cochrane Central Register of Controlled Trials
      (CENTRAL Issue 7 of 12, The Cochrane Library July 2013), and MEDLINE (1946 to 8
      August 2013). We did not impose any language restrictions. SELECTION CRITERIA: We
      considered all randomised and quasi-randomised parallel group studies either
      blinded or non-blinded. DATA COLLECTION AND ANALYSIS: Two review authors (BK and
      SR) independently screened the trials identified by the search. The same two
      authors planned to independently assess the methodological quality of studies. If
      studies had been identified for inclusion, one author would have extracted the
      data and the other would have verified it. MAIN RESULTS: No relevant studies were
      found. AUTHORS' CONCLUSIONS: There is no evidence to support or refute the use of
      subpial transection surgery for medically refractory cases of epilepsy. Well
      designed randomised controlled trials are needed in future to guide clinical
      practice.

PMID- 23963658
TI  - Estimation of the size of drug-like chemical space based on GDB-17 data.
AB  - The goal of this paper is to estimate the number of realistic drug-like molecules
      which could ever be synthesized. Unlike previous studies based on exhaustive
      enumeration of molecular graphs or on combinatorial enumeration preselected
      fragments, we used results of constrained graphs enumeration by Reymond to
      establish a correlation between the number of generated structures (M) and the
      number of heavy atoms (N): logM = 0.584 * N * logN + 0.356. The number of atoms
      limiting drug-like chemical space of molecules which follow Lipinsky's rules (N =
      36) has been obtained from the analysis of the PubChem database. This results in
      M ~ 1033 which is in between the numbers estimated by Ertl (1023) and by Bohacek
      (1060).

PMID- 23963659
TI  - Effects of sorafenib on energy metabolism in breast cancer cells: role of AMPK
      mTORC1 signaling.
AB  - In this study, we investigated the effects and the underlying molecular
      mechanisms of the multi-kinase inhibitor sorafenib in a panel of breast cancer
      cell lines. Sorafenib inhibited cell proliferation and induced apoptosis through
      the mitochondrial pathway. These effects were neither correlated with modulation
      of MAPK and AKT pathways nor dependent on the ERalpha status. Sorafenib promoted
      an early perturbation of mitochondrial function, inducing a deep depolarization
      of mitochondrial membrane, associated with drop of intracellular ATP levels and
      increase of ROS generation. As a response to this stress condition, the energy
      sensor AMPK was rapidly activated in all the cell lines analyzed. In MCF-7 and
      SKBR3 cells, AMPK enhanced glucose uptake by up-regulating the expression of GLUT
      1 glucose transporter, as also demonstrated by AMPKalpha1 RNA interference, and
      stimulated aerobic glycolysis thus increasing lactate production. Moreover, the
      GLUT-1 inhibitor fasentin blocked sorafenib-induced glucose uptake and
      potentiated its cytotoxic activity in SKBR3 cells. Persistent activation of AMPK
      by sorafenib finally led to the impairment of glucose metabolism both in MCF-7
      and SKBR3 cells as well as in the highly glycolytic MDA-MB-231 cells, resulting
      in cell death. This previously unrecognized long-term effect of sorafenib was
      mediated by AMPK-dependent inhibition of the mTORC1 pathway. Suppression of
      mTORC1 activity was sufficient for sorafenib to hinder glucose utilization in
      breast cancer cells, as demonstrated by the observation that the mTORC1 inhibitor
      rapamycin induced a comparable down-regulation of GLUT-1 expression and glucose
      uptake. The key role of AMPK-dependent inhibition of mTORC1 in sorafenib
      mechanisms of action was confirmed by AMPKalpha1 silencing, which restored mTORC1
      activity conferring a significant protection from cell death. This study provides
      insights into the molecular mechanisms driving sorafenib anti-tumoral activity in
      breast cancer, and supports the need for going on with clinical trials aimed at
      proving the efficacy of sorafenib for breast cancer treatment.

PMID- 23963660
TI  - GSK3beta inhibition and LEF1 upregulation in skeletal muscle following a bout of
      downhill running.
AB  - Canonical Wnt signaling is important in skeletal muscle repair but has not been
      well characterized in response to physiological stimuli. The objective of this
      study was to assess the effect of downhill running (DHR) on components of Wnt
      signaling. Young, male C57BL/J6 mice were exposed to DHR. Muscle injury and
      repair (MCadherin) were measured in soleus. Gene and protein expression of Wnt3a,
      active beta-catenin, GSK3beta, and LEF1 were measured in gastrocnemius. Muscle
      injury increased 6 days post-DHR and MCadherin protein increased 5 days post-DHR.
      Total and active GSK3beta protein decreased 3 days (9-fold and 3.6-fold,
      respectively) post-DHR. LEF1 protein increased 6 days (5-fold) post-DHR. DHR
      decreased GSK3beta and increased LEF1 protein expression, but did not affect
      other components of Wnt signaling. Due to their applicability, using models of
      physiological stimuli such as DHR will provide significant insight into cellular
      mechanisms within muscle. 

PMID- 23963661
TI  - Role of standardized grape polyphenol preparation as a novel treatment to improve
      synaptic plasticity through attenuation of features of metabolic syndrome in a
      mouse model.
AB  - SCOPE: Metabolic syndrome has become an epidemic and poses tremendous burden on
      the health system. People with metabolic syndrome are more likely to experience
      cognitive decline. As obesity and sedentary lifestyles become more common, the
      development of early prevention strategies is critical. In this study, we explore
      the potential beneficial effects of a combinatory polyphenol preparation composed
      of grape seed extract, Concord purple grape juice extract, and resveratrol,
      referred to as standardized grape polyphenol preparation (SGP), on peripheral as
      well as brain dysfunction induced by metabolic syndrome. METHODS AND RESULTS: We
      found dietary fat content had minimal effect on absorption of metabolites of
      major polyphenols derived from SGP. Using a diet-induced animal model of
      metabolic syndrome (DIM), we found that brain functional connectivity and
      synaptic plasticity are compromised in the DIM mice. Treatment with SGP not only
      prevented peripheral metabolic abnormality but also improved brain synaptic
      plasticity. CONCLUSION: Our study demonstrated that SGP, comprised of multiple
      bioavailable and bioactive components targeting a wide range of metabolic
      syndrome related pathological features, provides greater global protection
      against peripheral and central nervous system dysfunctions and can be potentially
      developed as a novel prevention/treatment for improving brain connectivity and
      synaptic plasticity important for learning and memory.

PMID- 23963662
TI  - Comparison of the effectiveness of different counseling methods before second
      trimester genetic amniocentesis in Thailand.
AB  - OBJECTIVE: The objective of this study is to compare the effectiveness of
      counseling methods before second trimester genetic amniocentesis. STUDY DESIGN:
      The design of this study is a randomized controlled study comparing the
      improvement in patients' knowledge satisfaction anxiety and perceived pain
      between computer-assisted instruction (CAI) and leaflet self-reading (LSR) and
      subsequent individual counseling among pregnant women scheduled for second
      trimester genetic amniocentesis in a developing country. RESULTS: There were 164
      and 157 participants in the LSR and CAI groups, respectively. In both groups,
      knowledge improved significantly after LSR/CAI (p < 0.001) and increased further
      after individual counseling (p < 0.001). After combined counseling, knowledge was
      significantly higher in the LSR than in the CAI group (p = 0.032). Knowledge was
      associated with higher level of education and previous exposure to genetic
      counseling. Pain decreased more in the CAI than in the LSR group after completion
      of counseling (p = 0.021). Reduction in anxiety and increase in satisfaction did
      not differ between the groups. Counseling method did not affect the final
      decision of patients to accept amniocentesis. CONCLUSION: Both counseling methods
      improved patients' knowledge and satisfaction and reduced pain and anxiety. In
      combination with individual counseling, LSR was more effective than CAI in
      improving patients' knowledge before second trimester genetic amniocentesis.

PMID- 23963663
TI  - Management of Right Ventricular Failure in Pulmonary Hypertension (and After LVAD
      Implantation).
AB  - OPINION STATEMENT: Right ventricular failure (RVF) is increasingly recognized as
      a complicating feature of a number of disease states, including pulmonary
      arterial hypertension (PAH) and advanced heart failure. It not only contributes
      to symptoms and complicates management, but also dramatically impacts prognosis.
      In PAH, early disease detection and institution of PAH therapy can prevent or
      delay RVF. Once established, therapy for RVF focuses on optimizing afterload
      reduction with PAH therapy, controlling volume, and judiciously using inotropic
      support when needed. In patients undergoing implantation of a LVAD, preoperative
      assessment and management of RVF is critical. Risk factors for the development of
      RVF after LVAD have been described, and may identify a population best managed
      with biventricular support. Postoperative management of RVF focuses on supportive
      therapy, judicious use of inotropes and volume management. Ongoing research may
      yield insights into specific therapies to prevent or reverse RVF.

PMID- 23963664
TI  - Can controlled ice nucleation improve freeze-drying of highly-concentrated
      protein formulations?
AB  - The aim of this study was to investigate if controlled ice nucleation with our
      previouly published method is applicable to highly-concentrated protein
      formulations of bovine serum albumin (100 mg/ml and 193.9 mg/ml) and a monoclonal
      antibody (161.2 mg/ml) and if positive effects on primary drying time as well as
      reconstitution times can be achieved. We observed that for both proteins, ice
      nucleation at a product temperature of -5  degrees C significantly reduced
      primary drying time. Furthermore, reconstitution times of the lyophilized cakes
      could be shortened, especially for the monoclonal antibody formulation with a
      reconstitution time of 5 minutes instead of 15 minutes.

PMID- 23963665
TI  - Structure reassignment of laurefurenynes A and B by computation and total
      synthesis.
AB  - The originally assigned stereostructures of laurefurenynes A and B have been
      reassigned on the basis of DFT calculations of NMR chemical shifts, synthesis of
      model compounds and total synthesis of laurefurenyne B, demonstrating the power
      of this combined approach for stereostructure elucidation/confirmation. 

PMID- 23963667
TI  - Finasteride for prostate cancer prevention has no effect on survival, study
      finds.

PMID- 23963669
TI  - US obesity rates are leveling out, but long term effects raise concern.

PMID- 23963670
TI  - Bacterial and archaeal communities in the acid pit lake sediments of a
      chalcopyrite mine.
AB  - Bacterial and archaeal community structures and diversity of three different
      sedimentary environments (BH1A, BH2A and BH3A) in the acid pit lake of a
      chalcopyrite mine at Touro (Spain) were determined by 16S rRNA gene PCR-DGGE and
      sequencing of clone libraries. DGGE of bacterial and archaeal amplicons showed
      that the sediments harbor different communities. Bacterial 16S rRNA gene
      sequences were assigned to Acidobacteria, Actinobacteria, Cyanobacteria,
      Planctomycetes, Proteobacteria, Chloroflexi and uncultured bacteria, after
      clustering into 42 operational taxonomic units (OTUs). OTU 2 represented
      approximately 37, 42 and 37 % of all sequences from sediments BH1A, BH2A and
      BH3A, respectively, and was phylogenetically related to uncultured Chloroflexi.
      Remaining OTUs were phylogenetically related to heterotrophic bacteria, including
      representatives of Ferrithrix and Acidobacterium genera. Archaeal 16S rRNA gene
      sequences were clustered into 54 OTUs. Most of the sequences from the BH1A
      sediment were assigned to Euryarchaeota, whereas those from BH2A sediment were
      assigned to Crenarchaeota. The majority of the sequences from BH3A sediment were
      assigned to unclassified Archaea, and showed similarities to uncultured and
      unclassified environmental clones. No sequences related to Acidithiobacillus and
      Leptospirillum, commonly associated with acid mine drainage, were detected in
      this study. 

PMID- 23963671
TI  - A theoretical framework to study potassium utilization efficiency in response to
      withdrawal of potassium.
AB  - An important objective of plant research is to improve the efficiency in the
      utilization of major nutrients, particularly nitrogen, phosphorus, and potassium.
      Several definitions of internal nutrient utilization efficiency (NUE) have been
      proposed, but the theoretical consistence of their use has been poorly explored.
      Here, a non-mechanistic approach was developed to theoretically examine the
      dynamics of commonly used NUE indicators following complete potassium
      deprivation. This approach was used to study the sensitivity of NUE indicators to
      changes in the actual NUE (NUEa) of K(+) in virtual plants. Three empirically
      based models that differ in the relationship between NUE and the internal K(+)
      concentration were examined. Frequently used indicators (potassium use
      efficiency, utilization efficiency, physiological efficiency, and nutrient
      productivity) and two additional ones introduced here (accumulated productivity
      and physiological ratio) differed in their capacity to reflect differences in
      NUEa. They also exhibited large disparities in their temporal variation and in
      their responsiveness to the concentration of K(+) before the beginning of the
      deprivation period. According to this analysis, the simultaneous use of several
      indicators could help to refine plant breeding for high NUE. The data also
      suggest that a trade off between plant productivity and the time necessary to
      reduce the concentration of K(+) by half is inherent to the dynamics of plant
      systems. Finally, it is proposed that for some plant species selection for high
      NUEa would not always be in conflict with selection for improved relative plant
      performance in low K(+) environments. 

PMID- 23963672
TI  - Soybean GmbZIP123 gene enhances lipid content in the seeds of transgenic
      Arabidopsis plants.
AB  - Soybean is one of most important oil crops and a significant increase in lipid
      content in soybean seeds would facilitate vegetable oil production in the world.
      Although the pathways for lipid biosynthesis in higher plants have been
      uncovered, our understanding of regulatory mechanism controlling lipid
      accumulation is still limited. In this study, we identified 87 transcription
      factor genes with a higher abundance at the stage of lipid accumulation in
      soybean seeds. One of these genes, GmbZIP123, was selected to further study its
      function in regulation of lipid accumulation. Overexpression of GmbZIP123
      enhanced lipid content in the seeds of transgenic Arabidopsis thaliana plants.
      The GmbZIP123 transgene promoted expression of two sucrose transporter genes
      (SUC1 and SUC5) and three cell-wall invertase genes (cwINV1, cwINV3, and cwINV6)
      by binding directly to the promoters of these genes. Consistently, the cell-wall
      invertase activity and sugar translocation were all enhanced in siliques of
      GmbZIP123 transgenic plants. Higher levels of glucose, fructose, and sucrose were
      also found in seeds of GmbZIP123 transgenic plants. These results suggest that
      GmbZIP123 may participate in regulation of lipid accumulation in soybean seeds by
      controlling sugar transport into seeds from photoautotrophic tissues. This study
      provides novel insights into the regulatory mechanism for lipid accumulation in
      seeds and may facilitate improvements in oil production in soybean and other oil
      crops through genetic manipulation of the GmbZIP123 gene. 

PMID- 23963673
TI  - AtrbohD and AtrbohF positively regulate abscisic acid-inhibited primary root
      growth by affecting Ca2+ signalling and auxin response of roots in Arabidopsis.
AB  - Reactive oxygen species (ROS) originating from the NADPH oxidases AtrbohD and
      AtrbohF play an important role in abscisic acid (ABA)-inhibited primary root
      growth in Arabidopsis. However, the mechanisms underlying this process remain
      elusive. In this study, the double mutant atrbohD1/F1 and atrbohD2/F2, in which
      both AtrbohD and AtrbohF were disrupted, were less sensitive to ABA suppression
      of root cell elongation than wild-type (WT) plants. Furthermore, the double
      mutants showed impaired ABA responses in roots, including ROS generation,
      cytosolic Ca(2+) increases, and activation of plasma membrane Ca(2+)-permeable
      channels compared with WT. Exogenous H2O2 can activate the Ca(2+) currents in
      roots of atrbohD1/F1. In addition, exogenous application of the auxin transport
      inhibitor naphthylphthalamic acid effectively promoted ABA inhibition of root
      growth of the mutants relative to that of WT. The ABA-induced decreases in auxin
      sensitivity of the root tips were more pronounced in WT than in atrbohD1/F1.
      These findings suggest that both AtrbohD and AtrbohF are essential for ABA
      promoted ROS production in roots. ROS activate Ca(2+) signalling and reduce auxin
      sensitivity of roots, thus positively regulating ABA-inhibited primary root
      growth in Arabidopsis. 

PMID- 23963674
TI  - Nitrogen metabolism of two contrasting poplar species during acclimation to
      limiting nitrogen availability.
AB  - To investigate N metabolism of two contrasting Populus species in acclimation to
      low N availability, saplings of slow-growing species (Populus popularis, Pp) and
      a fast-growing species (Populus alba * Populus glandulosa, Pg) were exposed to
      10, 100, or 1000 MUM NH4NO3. Despite greater root biomass and fine root surface
      area in Pp, lower net influxes of NH4(+) and NO3(-) at the root surface were
      detected in Pp compared to those in Pg, corresponding well to lower NH4(+) and
      NO3(-) content and total N concentration in Pp roots. Meanwhile, higher stable N
      isotope composition (delta(15)N) in roots and stronger responsiveness of
      transcriptional regulation of 18 genes involved in N metabolism were found in
      roots and leaves of Pp compared to those of Pg. These results indicate that the N
      metabolism of Pp is more sensitive to decreasing N availability than that of Pg.
      In both species, low N treatments decreased net influxes of NH4(+) and NO3(-),
      root NH4(+) and foliar NO3(-) content, root NR activities, total N concentration
      in roots and leaves, and transcript levels of most ammonium (AMTs) and nitrate
      (NRTs) transporter genes in leaves and genes involved in N assimilation in roots
      and leaves. Low N availability increased fine root surface area, foliar starch
      concentration, delta(15)N in roots and leaves, and transcript abundance of
      several AMTs (e.g. AMT1;2) and NRTs (e.g. NRT1;2 and NRT2;4B) in roots of both
      species. These data indicate that poplar species slow down processes of N
      acquisition and assimilation in acclimation to limiting N supply.

PMID- 23963676
TI  - Uncorrelated evolution of leaf and petal venation patterns across the angiosperm
      phylogeny.
AB  - Early angiosperm evolution, beginning approximately 140 million years ago, saw
      many innovations that enabled flowering plants to alter ecosystems globally.
      These included the development of novel, flower-based pollinator attraction
      mechanisms and the development of increased water transport capacity in stems and
      leaves. Vein length per area (VLA) of leaves increased nearly threefold in the
      first 30-40 million years of angiosperm evolution, increasing the capacity for
      transpiration and photosynthesis. In contrast to leaves, high water transport
      capacities in flowers may not be an advantage because flowers do not typically
      contribute to plant carbon gain. Although flowers of extant basal angiosperms are
      hydrated by the xylem, flowers of more recently derived lineages may be hydrated
      predominantly by the phloem. In the present study, we measured leaf and flower
      VLA for a phylogenetically diverse sample of 132 species from 52 angiosperm
      families to ask (i) whether flowers have lower VLA than leaves, (ii) whether
      flowers of basal angiosperm lineages have higher VLA than more recently derived
      lineages because of differences between xylem and phloem hydration, and (iii)
      whether flower and leaf VLA evolved independently. It was found that floral
      structures had lower VLA than leaves, but basal angiosperm flowers did not have
      higher VLA than more derived lineages. Furthermore, the independent evolution of
      leaf and petal VLA suggested that these organs may be developmentally modular.
      Unlike leaves, which have experienced strong selection for increased water
      transport capacity, flowers may have been shielded from such selective pressures
      by different developmental processes controlling VLA throughout the plant
      bauplan. 

PMID- 23963675
TI  - A mutation in the FZL gene of Arabidopsis causing alteration in chloroplast
      morphology results in a lesion mimic phenotype.
AB  - Lesion mimic mutants (LMMs) are a class of mutants in which hypersensitive cell
      death and defence responses are constitutively activated in the absence of
      pathogen attack. Various signalling molecules, such as salicylic acid (SA),
      reactive oxygen species (ROS), nitric oxide (NO), Ca(2+), ethylene, and
      jasmonate, are involved in the regulation of multiple pathways controlling
      hypersensitive response (HR) activation, and LMMs are considered useful tools to
      understand the role played by the key elements of the HR cell death signalling
      cascade. Here the characterization of an Arabidopsis LMM lacking the function of
      the FZL gene is reported. This gene encodes a membrane-remodelling GTPase playing
      an essential role in the determination of thylakoid and chloroplast morphology.
      The mutant displayed alteration in chloroplast number, size, and shape, and the
      typical characteristics of an LMM, namely development of chlorotic lesions on
      rosette leaves and constitutive expression of genetic and biochemical markers
      associated with defence responses. The chloroplasts are a major source of ROS,
      and the characterization of this mutant suggests that their accumulation,
      triggered by damage to the chloroplast membranes, is a signal sufficient to start
      the HR signalling cascade, thus confirming the central role of the chloroplast in
      HR activation. 

PMID- 23963677
TI  - NEVERSHED and INFLORESCENCE DEFICIENT IN ABSCISSION are differentially required
      for cell expansion and cell separation during floral organ abscission in
      Arabidopsis thaliana.
AB  - Floral organ shedding is a cell separation event preceded by cell-wall loosening
      and generally accompanied by cell expansion. Mutations in NEVERSHED (NEV) or
      INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) block floral organ abscission in
      Arabidopsis thaliana. NEV encodes an ADP-ribosylation factor GTPase-activating
      protein, and cells of nev mutant flowers display membrane-trafficking defects.
      IDA encodes a secreted peptide that signals through the receptor-like kinases
      HAESA (HAE) and HAESA-LIKE2 (HSL2). Analyses of single and double mutants
      revealed unique features of the nev and ida phenotypes. Cell-wall loosening was
      delayed in ida flowers. In contrast, nev and nev ida mutants displayed ectopic
      enlargement of abscission zone (AZ) cells, indicating that cell expansion alone
      is not sufficient to trigger organ loss. These results suggest that NEV initially
      prevents precocious cell expansion but is later integral for cell separation. IDA
      is involved primarily in the final cell separation step. A mutation in KNOTTED
      LIKE FROM ARABIDOPSIS THALIANA1 (KNAT1), a suppressor of the ida mutant, could
      not rescue the abscission defects of nev mutant flowers, indicating that NEV
      dependent activity downstream of KNAT1 is required. Transcriptional profiling of
      mutant AZs identified gene clusters regulated by IDA-HAE/HSL2. Several genes were
      more strongly downregulated in nev-7 compared with ida and hae hsl2 mutants,
      consistent with the rapid inhibition of organ loosening in nev mutants, and the
      overlapping roles of NEV and IDA in cell separation. A model of the crosstalk
      between the IDA signalling pathway and NEV-mediated membrane traffic during
      floral organ abscission is presented. 

PMID- 23963678
TI  - Mn tolerance in rice is mediated by MTP8.1, a member of the cation diffusion
      facilitator family.
AB  - Manganese (Mn) is an essential micronutrient for plants, but is toxic when
      present in excess. The rice plant (Oryza sativa L.) accumulates high
      concentrations of Mn in the aerial parts; however, the molecular basis for Mn
      tolerance is poorly understood. In the present study, genes encoding Mn tolerance
      were screened for by expressing cDNAs of genes from rice shoots in Saccharomyces
      cerevisiae. A gene encoding a cation diffusion facilitator (CDF) family member,
      OsMTP8.1, was isolated, and its expression was found to enhance Mn accumulation
      and tolerance in S. cerevisiae. In plants, OsMTP8.1 and its transcript were
      mainly detected in shoots. High or low supply of Mn moderately induced an
      increase or decrease in the accumulation of OsMTP8.1, respectively. OsMTP8.1 was
      detected in all cells of leaf blades through immunohistochemistry. OsMTP8.1 fused
      to green fluorescent protein was localized to the tonoplast. Disruption of
      OsMTP8.1 resulted in decreased chlorophyll levels, growth inhibition in the
      presence of high concentrations of Mn, and decreased accumulation of Mn in shoots
      and roots. However, there was no difference in the accumulation of other metals,
      including Zn, Cu, Fe, Mg, Ca, and K. These results suggest that OsMTP8.1 is an Mn
      specific transporter that sequesters Mn into vacuoles in rice and is required for
      Mn tolerance in shoots. 

PMID- 23963679
TI  - ATP-competitive mTOR kinase inhibitors delay plant growth by triggering early
      differentiation of meristematic cells but no developmental patterning change.
AB  - The TOR (target of rapamycin) protein, a large phosphatidylinositol 3-kinase-like
      protein kinase (PIKK) that is conserved in eukaryotes and is a central regulator
      of growth and metabolism. The analysis of function of TOR in plant growth and
      development has been limited by the fact that plants are very poorly sensitive to
      rapamycin. As the kinase domain of TOR is highly conserved, this study analysed
      the dose-dependent effect of three sets of first- and second-generation ATP
      competitive inhibitors (called asTORis for active-site TOR inhibitors) recently
      developed for the human TOR kinase on Arabidopsis thaliana growth. All six
      asTORis inhibited plant root growth in a dose-dependent manner, with 50% growth
      inhibitory doses (GI50) of <10 MUM and <1 MUM for the first- and second
      generation inhibitors, respectively, similarly to the values in mammalian cells.
      A genetic approach further demonstrated that only asTORis inhibited root growth
      in an AtTOR gene-dosage-dependent manner. AsTORis decreased the length of: (i)
      the meristematic zone (MZ); (ii) the division zone in the MZ; (iii) epidermal
      cells in the elongation zone; and (iv) root hair cells. Whereas meristematic
      cells committed to early differentiation, the pattern of cell differentiation was
      not affected per se. AsTORis-induced root hair growth phenotype was shown to be
      specific by using other growth inhibitors blocking the cell cycle or translation.
      AsTORis dose-dependent inhibition of growth and root hairs was also observed in
      diverse groups of flowering plants, indicating that asTORis can be used to study
      the TOR pathway in other angiosperms, including crop plants. 

PMID- 23963680
TI  - Sensitive multiplex detection of serological liver cancer biomarkers using SERS
      active photonic crystal fiber probe.
AB  - Surface-enhanced Raman scattering (SERS) spectroscopy possesses the most
      promising advantage of multiplex detection for biosensing applications, which is
      achieved due to the narrow 'fingerprint' Raman spectra from the analyte
      molecules. We developed an ultrasensitive platform for the multiplex detection of
      cancer biomarkers by combining the SERS technique with a hollow-core photonic
      crystal fiber (HCPCF). Axially aligned air channels inside the HCPCF provide an
      excellent platform for optical sensing using SERS. In addition to the flexibility
      of optical fibers, HCPCF provides better light confinement and a larger
      interaction length for the guided light and the analyte, resulting in an
      improvement in sensitivity to detect low concentrations of bioanalytes in
      extremely low sample volumes. Herein, for the first time, we demonstrate the
      sensitive multiplex detection of biomarkers immobilized inside the HCPCF using
      antibody-conjugated SERS-active nanoparticles (SERS nanotags). As a proof-of
      concept for targeted multiplex detection, initially we carried out the sensing of
      epidermal growth factor receptor (EGFR) biomarker in oral squamous carcinoma cell
      lysate using three different SERS nanotags. Subsequently, we also achieved
      simultaneous detection of hepatocellular carcinoma (HCC) biomarkers-alpha
      fetoprotein (AFP) and alpha-1-antitrypsin (A1AT) secreted in the supernatant from
      Hep3b cancer cell line. Using a SERS-HCPCF sensing platform, we could
      successfully demonstrate the multiplex detection in an extremely low sample
      volume of ~20 nL. In future, this study may lead to sensitive biosensing platform
      for the low concentration detection of biomarkers in an extremely low sample
      volume of body fluids to achieve early diagnosis of multiple diseases. ((c) 2014
      WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim). 

PMID- 23963682
TI  - Surgical treatment of early-stage thymomas: robot-assisted thoracoscopic surgery
      versus transsternal thymectomy.
AB  - BACKGROUND: This study aimed to compare the perioperative outcomes for patients
      who underwent transsternal or robot-assisted thymectomy and to determine the
      feasibility of robot-assisted thymectomy for the treatment of Masaoka stages 1
      and 2 thymomas. METHODS: The study evaluated the short-term outcomes for 74
      patients undergoing surgery for Masaoka stages 1 and 2 thymomas without
      myasthenia gravis between January 2009 and December 2012. Of these 74 patients,
      23 underwent thymoma resection using unilateral robot-assisted thoracoscopic
      surgery (RATS group), and 51 underwent transsternal thymectomy (TST group).
      Duration of surgery, amount of intraoperative blood loss, duration of chest
      drainage, duration of postoperative hospital stay, and postoperative
      complications were evaluated. RESULTS: The intraoperative blood loss was
      significantly less in the RATS groups (61.3 ml) than in the TST group (466.1 ml)
      (p < 0.01). The postoperative hospital stay was significantly shorter in the RATS
      group (3.7 vs 11.6 days; p < 0.01). No patients in the RATS group underwent
      conversion to open surgery. No severe surgical complications (e.g., bleeding
      caused by injury to the left brachiocephalic vein) and only one case of pulmonary
      atelectasis (appearing in a male patient 2 days after surgery) were detected in
      this series. CONCLUSION: Robot-assisted thoracoscopic thymectomy for early-stage
      thymomas is technically feasible, safe, and less invasive for the patient.

PMID- 23963684
TI  - A systematic review of Internet-based supportive interventions for caregivers of
      patients with dementia.
AB  - OBJECTIVE: Because of the expected increase in the number of dementia patients,
      the unlikelihood of a cure in the near future, and the rising cost of care, there
      is an increasing need for effective caregiver interventions. Internet
      interventions hold considerable promise for meeting the educational and support
      needs of informal dementia caregivers at reduced costs. The current study aims to
      provide an overview of the evidence for the effectiveness, feasibility, and
      quality of Internet interventions for informal caregivers of people with
      dementia. METHODS: A systematic literature search of five scientific databases
      was performed, covering literature published up to 10 January 2013. Twelve
      studies were identified. The quality of the included studies was assessed
      according to the Cochrane level of evidence and the criteria list of the Cochrane
      Back Review Group. RESULTS: The intervention types, dosage, and duration differed
      widely, as did the methodological quality of the included studies. The overall
      level of evidence was low. However, the results demonstrate that Internet
      interventions for informal dementia caregivers can improve various aspects of
      caregiver well-being, for example, confidence, depression, and self-efficacy,
      provided they comprise multiple components and are tailored to the individual.
      Furthermore, caregivers could benefit from interaction with a coach and other
      caregivers. CONCLUSIONS: Internet interventions for informal dementia caregivers
      may improve caregiver well-being. However, the available supporting evidence
      lacks methodological quality. More randomized controlled studies assessing
      interventions performed according to protocol are needed to give stronger
      statements about the effects of supportive Internet interventions and their most
      promising elements.

PMID- 23963683
TI  - Protein kinase inhibitor gamma reciprocally regulates osteoblast and adipocyte
      differentiation by downregulating leukemia inhibitory factor.
AB  - The protein kinase inhibitor (Pki) gene family inactivates nuclear protein kinase
      A (PKA) and terminates PKA-induced gene expression. We previously showed that
      Pkig is the primary family member expressed in osteoblasts and that Pkig
      knockdown increases the effects of parathyroid hormone and isoproterenol on PKA
      activation, gene expression, and inhibition of apoptosis. Here, we determined
      whether endogenous levels of Pkig regulate osteoblast differentiation. Pkig is
      the primary family member in murine embryonic fibroblasts (MEFs), murine marrow
      derived mesenchymal stem cells, and human mesenchymal stem cells. Pkig deletion
      increased forskolin-dependent nuclear PKA activation and gene expression and Pkig
      deletion or knockdown increased osteoblast differentiation. PKA signaling is
      known to stimulate adipogenesis; however, adipogenesis and osteogenesis are often
      reciprocally regulated. We found that the reciprocal regulation predominates over
      the direct effects of PKA since adipogenesis was decreased by Pkig deletion or
      knockdown. Pkig deletion or knockdown also simultaneously increased osteogenesis
      and decreased adipogenesis in mixed osteogenic/adipogenic medium. Pkig deletion
      increased PKA-induced expression of leukemia inhibitory factor (Lif) mRNA and LIF
      protein. LIF neutralizing antibodies inhibited the effects on osteogenesis and
      adipogenesis of either Pkig deletion in MEFs or PKIgamma knockdown in both murine
      and human mesenchymal stem cells. Collectively, our results show that endogenous
      levels of Pkig reciprocally regulate osteoblast and adipocyte differentiation and
      that this reciprocal regulation is mediated in part by LIF. Stem Cells
      2013;31:2789-2799. 

PMID- 23963685
TI  - Evaluation of the in vitro biocompatibility of PMMA/high-load HA/carbon
      nanostructures bone cement formulations.
AB  - Although commercially-available poly(methyl methacrylate) bone cement is widely
      used in total joint replacements, it has many shortcomings, a major one being
      that it does not osseointegrate with the contiguous structures. We report on the
      in vitro evaluation of the biocompatibility of modified formulations of the
      cement in which a high loading of hydroxyapatite (67 wt/wt%), an extra amount of
      benzoyl peroxide, and either 0.1 wt/wt% functionalized carbon nanotubes or 0.5
      wt/wt% graphene oxide was added to the cement powder and an extra amount of
      dimethyl-p-toluidiene was added to the cement's liquid monomer. This evaluation
      was done using mouse L929 fibroblasts and human Saos-2 osteoblasts. For each
      combination of cement formulation and cell type, there was high cell viability,
      low apoptosis, and extensive spread on disc surfaces. Thus, these two cement
      formulations may have potential for use in the clinical setting. 

PMID- 23963681
TI  - Metabolic function of the CTRP family of hormones.
AB  - Maintaining proper energy balance in mammals entails intimate crosstalk between
      various tissues and organs. These inter-organ communications are mediated, to a
      great extent, by secreted hormones that circulate in blood. Regulation of the
      complex metabolic networks by secreted hormones (e.g., insulin, glucagon, leptin,
      adiponectin, FGF21) constitutes an important mechanism governing the integrated
      control of whole-body metabolism. Disruption of hormone-mediated metabolic
      circuits frequently results in dysregulated energy metabolism and pathology. As
      part of an effort to identify novel metabolic hormones, we recently characterized
      a highly conserved family of 15 secreted proteins, the C1q/TNF-related proteins
      (CTRP1-15). While related to adiponectin in sequence and structural organization,
      each CTRP has its own unique tissue expression profile and non-redundant function
      in regulating sugar and/or fat metabolism. Here, we summarize the current
      understanding of the physiological functions of CTRPs, emphasizing their
      metabolic roles. Future studies using gain-of-function and loss-of-function mouse
      models will provide greater mechanistic insights into the critical role CTRPs
      play in regulating systemic energy homeostasis. 

PMID- 23963686
TI  - Integration of single-layer skin hollow fibers and scaffolds develops a three
      dimensional hybrid bioreactor for bioartificial livers.
AB  - Bioartificial liver support systems are expected to be an effective therapy as a
      "bridge" for liver transplantation or reversible acute liver disease. A major
      roadblock in the application of bioartificial livers is the need for a bioreactor
      that fully meets the requirements of hepatocyte culture, mass transfer and
      immunobarriers. In this study, we developed a three-dimensional hybrid bioreactor
      (3DHB) on a base of single-layer skin polyethersulfone hollow fibers by
      integrating with polyurethane scaffolds. The mass transfer of bilirubin and
      albumin from the intracapillary space to the extracapillary space of the hollow
      fibers was not significantly different between 3DHBs and hollow fiber bioreactors
      (HFBs). Cell viability staining showed that high-density hepatocytes were
      uniformly found in different regions of the 3DHB after 7 days of culture. Liver
      specific functions of human mature hepatocytes cultured in the 3DHB, such as
      albumin secretion, urea production, ammonia removal rate and cytochrome P450
      activity, were maintained stably and were significantly higher compared with the
      HFB. These results indicated that the 3DHB has good mass transfer and improves
      cell distribution and liver-specific functions. Meanwhile, the ammonia and
      unconjugated bilirubin concentrations in plasma from patients with liver failure
      were significantly decreased during 6 h of circulation by hepatocytes cultured in
      the 3DHB. Most hepatocytes in the 3DHB were viable after 6 h exposure to the
      patient plasma. We further demonstrated that bioartificial liver systems with
      3DHB can remove toxins from and endure the deleterious effects of the patient
      plasma. Therefore, the 3DHB has the potential to accomplish different actions for
      the clinical application of bioartificial livers.

PMID- 23963687
TI  - Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus
      aureus (MRSA) infections in surgical wounds.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection after
      surgery is usually rare, but incidence can be up to 33% in certain types of
      surgery. Postoperative MRSA infection can occur as surgical site infections
      (SSI), chest infections, or bloodstream infections (bacteraemia). The incidence
      of MRSA SSIs varies from 1% to 33% depending upon the type of surgery performed
      and the carrier status of the individuals concerned. The optimal antibiotic
      regimen for the treatment of MRSA in surgical wounds is not known. OBJECTIVES: To
      compare the benefits and harms of various antibiotic treatments in people with
      established surgical site infections (SSIs) caused by MRSA . SEARCH METHODS: In
      February 2013 we searched the following databases: The Cochrane Wounds Group
      Specialised Register; The Cochrane Central Register of Controlled Trials
      (CENTRAL); Database of Abstracts of Reviews of Effects (DARE); NHS Economic
      Evaluation Database; Health Technology Assessment (HTA) Database; Ovid MEDLINE;
      Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO
      CINAHL. SELECTION CRITERIA: We included only randomised controlled trials (RCTs)
      comparing one antibiotic regimen with another antibiotic regimen for the
      treatment of SSIs due to MRSA. All RCTs irrespective of language, publication
      status, publication year, or sample size were included in the analysis. DATA
      COLLECTION AND ANALYSIS: Two review authors independently decided on inclusion
      and exclusion of trials, and extracted data. We planned to calculate the risk
      ratio (RR) with 95% confidence intervals (CI) for comparing the binary outcomes
      between the groups and mean difference (MD) with 95% CI for comparing the
      continuous outcomes. We planned to perform the meta-analysis using both a fixed
      effect and a random-effects model. We performed intention-to-treat analysis
      whenever possible. MAIN RESULTS: We included one trial involving 59 people
      hospitalised because of MRSA SSIs. Thirty participants were randomised to
      linezolid (600 mg either intravenously or orally every 12 hours for seven to 14
      days) and 29 to vancomycin (1 g intravenously every 12 hours for seven to 14
      days). The type of surgical procedures that were performed were not reported. The
      trial reported one outcome, which was the eradication of MRSA. The proportion of
      people in whom MRSA was eradicated was statistically significantly higher in the
      linezolid group than in the vancomycin group (RR 1.80; 95% CI 1.20 to 2.68).
      AUTHORS' CONCLUSIONS: There is currently no evidence to recommend any specific
      antibiotic in the treatment of MRSA SSIs. Linezolid is superior to vancomycin in
      the eradication of MRSA SSIs on the basis of evidence from one small trial that
      was at high risk of bias, but the overall clinical implications of using
      linezolid instead of vancomycin are not known. Further well-designed randomised
      clinical trials are necessary in this area.

PMID- 23963688
TI  - Aspirin dose increase from 75 to 150 mg suppresses red blood cell contribution to
      suboptimal platelet response to aspirin in patients with CAD.
AB  - PURPOSE: To verify the hypothesis that erythrocytes play a role in suboptimal
      blood platelet response to acetylsalicylic acid (ASA, aspirin) in subjects with
      coronary artery disease (CAD). METHODS: In a cross-over randomized controlled
      intervention study we evaluated blood platelet response to 30-day treatment with
      75 mg/d or 150 mg/d of ASA (enteric coated) in CAD patients (n = 125). In vitro
      platelet response to collagen or arachidonic acid was monitored with impedance
      aggregometry and plasma thromboxane B2 was assayed immunoenzymatically. Blood
      morphology and several plasma biochemical parameters were determined using
      routine diagnostic procedures. RESULTS: CAD patients demonstrated lower blood
      platelet responsiveness to 75 mg/d of ASA compared to healthy subjects. The
      improved platelet responsiveness to 150 mg/d of ASA was particularly evident in
      "poor" responding patients. Positive correlations between platelet "poor"
      response to lower (75 mg/d) ASA dose and red blood cell count (Rs = 0.215; p <
      0.04), haemoglobin (Rs = 0.232; p < 0.02) and haematocrit (Rs = 0.239; p < 0.02)
      were found in CAD patients. Association between "poor" platelet response with
      lower ASA dose was confirmed by conditional maximum likelihood logistic
      regression, which showed the independency between erythrocyte-derived parameters,
      as the risk factors for suboptimal platelet response to ASA, and other risk
      factors, like CRP or LDL-cholesterol. In "poor" ASA responders taking the higher
      ASA dose (150 mg/d) the correlation between platelets' response to ASA and
      erythrocyte-derived parameters was not significant. CONCLUSIONS: Red blood cell
      parameters are associated with suboptimal blood platelet response to ASA in
      patients with CAD. Such a platelet refractoriness to ASA may be effectively
      overcome by increasing the ASA dose.

PMID- 23963689
TI  - Metabolic bone disease: a continued challenge in extremely low birth weight
      infants.
AB  - BACKGROUND: Metabolic bone disease (MBD) is an important prematurity-related
      morbidity, but remains inadequately investigated in extremely low birth weight
      (ELBW) infants, the group most at risk. The objective was to describe the
      incidence and associated risk factors of MBD in ELBW infants. METHODS:
      Retrospective analysis of all ELBW infants admitted between January 2005 and
      December 2010 who survived > 8 weeks. MBD was defined as the presence of
      osteopenia or rickets in radiographs. RESULTS: Of the 230 infants included in the
      study, 71 (30.9%) developed radiological evidence of MBD (cases) of which 24/71
      (33.8%) developed spontaneous fractures. MBD and fractures were noted at mean
      postnatal ages of 58.2 +/- 28 and 100.0 +/- 61 days, respectively. Compared with
      controls, cases were smaller at birth (664.6 +/- 146 g vs 798.1 +/- 129 g), more
      premature (25.0 +/- 1.8 vs 26.4 +/- 1.9 weeks), more frequently associated with
      mechanical ventilation, chronic lung disease, parenteral nutrition days,
      cholestasis, furosemide, postnatal steroids, and antibiotics use (all P < .01).
      Cases had lower average weekly intake of calcium, phosphorous, vitamin D,
      protein, and calories during the first 8 weeks of life compared with controls.
      Cases with MBD, compared with controls, had higher mortality (14.1 vs 4.4%) and
      longer hospital stay (140.2 +/- 51 vs 101.0 +/- 42 days; P < .01). CONCLUSIONS:
      MBD remains an important morbidity in ELBW infants despite advances in neonatal
      nutrition. Further research is needed to optimize the management of chronic lung
      disease and early nutrition in ELBW infants.

PMID- 23963690
TI  - Fish-oil fat emulsion supplementation reduces the risk of retinopathy in very low
      birth weight infants: a prospective, randomized study.
AB  - BACKGROUND: Preliminary studies suggest that fish-oil lipid emulsion given
      parenterally to very preterm infants reduces the severity of retinopathy (ROP)
      and cholestasis. METHODS: Infants weighing <1250 g at birth were randomly
      allocated to 2 groups: an experimental group of 60 infants that received an
      intravenous (IV) soybean, olive oil, and fish oil emulsion, and a control group
      of 70 infants that was given a parenteral soybean and olive oil emulsion. Plasma
      and erythrocyte concentrations of docosahexaenoic acid (DHA) were determined
      using a high-performance liquid chromatography-mass spectrometry analysis.
      RESULTS: Nine infants in the fish oil group required laser therapy for ROP
      compared with 22 infants in the standard intralipid group (risk ratio [RR], 0.48;
      95% confidence interval [CI], 0.24-0.96). Three infants in the fish oil group
      developed cholestasis compared with 20 infants in the standard intralipid group
      (RR, 0.18; 95% CI, 0.055-0.56). The mean plasma DHA concentrations in treated
      infants were 2.9-fold higher in the fish oil group than in control infants on the
      7th and 14th days of life. The mean DHA content in erythrocytes of treated
      infants was 4.5-fold and 2.7-fold higher compared with controls at 7 and 14 days
      of age. CONCLUSIONS: Premature infants receiving an IV fat emulsion containing
      fish oil had less ROP requiring laser treatment and less cholestasis than those
      receiving a standard lipid emulsion. These infants also had higher plasma and
      erythrocyte DHA levels at 7 and 14 days, suggesting potential long-term
      neurodevelopmental benefits.

PMID- 23963691
TI  - Comparative analysis of the efficacy and complications of nasojejunal and
      jejunostomy on patients undergoing pancreaticoduodenectomy.
AB  - BACKGROUND: The efficacy and feeding-related complications of a nasojejunal
      feeding tube and jejunostomy after pancreaticoduodenectomy (PD) was investigated
      with a randomized, controlled clinical trial at the Affiliated Drum Tower
      Hospital. METHODS: Sixty-eight patients who underwent PD in the Department of
      Hepatobiliary Surgery were randomly divided into 2 groups: 34 patients received
      enteral feeding via a nasojejunal tube (NJT group) and 34 patients received
      enteral feeding via a jejunostomy tube (JT group). The assessment of clinical
      outcome was based on postoperative investigation of complications. The second
      part of the assessment included tube related complications and an index on
      catheter efficiency. RESULTS: There were 15 cases with infectious complications
      in the JT group and 13 cases in the NJT group, and there was no significant
      difference in the rate of infectious complications between the 2 groups. The rate
      of intestinal obstruction and delayed gastric emptying was significantly
      decreased in the NJT group (P < .05). Catheter-related complications were more
      common in the JT group as compared with the NJT group (35.3% vs 20.6%, P < .05).
      The time for removal of the feeding tube and nasogastric tube was significantly
      decreased in the NJT group. The postoperative hospital stay in the NJT group was
      significantly decreased (P < .05), and there was no hospital mortality in this
      study. CONCLUSION: Nasojejunal feeding is safer than jejunostomy, and it is
      associated with only minor complications. Nasojejunal feeding can significantly
      decrease the incidence of delayed gastric emptying and shorten the postoperative
      hospital stay.

PMID- 23963692
TI  - Active Transportation in Kingston, Ontario: An Analysis of Mode, Destination,
      Duration, and Season Among Walkers and Cyclists.
AB  - BACKGROUND: Individuals that engage in active transportation (AT) have healthier
      weights and fitness levels. Most AT research has focused on work- or school-based
      destinations. Meanwhile, little is known about the differences between
      individuals that engage in the most common forms of AT--walking and cycling--and
      how these AT patterns vary by destination, duration, and season. METHODS: We
      recruited 1400 randomly sampled adults (350 per season) in Kingston, Ontario,
      Canada to complete a cross-sectional telephone survey. The survey captured the
      prevalence, destinations, and duration of AT, and we examined the observed
      differences by mode. RESULTS: The majority (72%) of respondents were AT-users;
      walking constituted 93% of overall mode share. Cyclists were more likely to be
      male, younger, and employed than walkers. Walkers tended to access neighborhood
      based destinations, while cyclists were more likely to use AT to get to work. AT
      duration was comparable by mode, ranging from approximately 8 to 20 minutes.
      Overall rates of AT were lowest in the winter, but walking rates were reasonably
      high year-round. CONCLUSIONS: Beyond commuting to work and school, policy-makers
      and planners should consider the breadth of destinations accessed by different
      modes when aiming to increase physical activity through AT in their communities.

PMID- 23963693
TI  - Anti-proliferative and apoptosis inducing effect of nimbolide by altering
      molecules involved in apoptosis and IGF signalling via PI3K/Akt in prostate
      cancer (PC-3) cell line.
AB  - Prostate cancer is responsible for major deaths globally after lung cancer.
      Nimbolide is an important constituent of neem, and it acts as a potent inhibitor
      for many cancer cells. The present study was designed to evaluate the effects of
      nimbolide on apoptosis and insulin-like growth factor (IGF) signalling molecules
      in androgen-independent prostate cancer (PC-3) cells line. Nimbolide (0.5-2 MUM)
      treatment resulted in 50% inhibition at a dose of 2 MUM in the PC-3 cell line.
      The mRNA expression of Fas ligand, Fas-associated death domain receptor (FADDR),
      Bcl-2-associated X protein (Bax), Bcl-2-associated death promoter (Bad),
      phosphatidylinositide 3-kinases (PI3K), Akt, IGF1, IGF1 receptor (IGF1R) and IGF
      binding protein 3 were quantified by reverse transcription polymerase chain
      reaction and protein expression of Bax, cytochrome c, X-linked inhibitor of
      apoptosis protein (XIAP), B-Cell Lymphoma 2 (Bcl-2), caspases -8, -9, -10 and -3,
      poly(ADP-ribose) polymerase (PARP), cleaved PARP, IGF1R, PI3K, Akt, p-Akt was
      determined by western blot analysis, in nimbolide-treated PC-3 cell line.
      Nimbolide-induced apoptosis by activating DNA fragmentation in PC-3 cells.
      Nimbolide treatment increased the mRNA of Fas ligand, FADDR, Bax, Bad and IGF
      binding protein 3, decreased PI3K, Akt, IGF1 and IGF1R, increased protein
      expression of caspases 8, 3, 10, 9, Bax and cytochrome c and decreased the
      expression of XIAP, Bcl2, cleaved PARP, p-Akt and IGF1R. The results suggest that
      nimbolide acts as a potent anti-cancer agent by inducing apoptosis and inhibiting
      cell proliferation via PI3K/Akt pathway in PC-3 cells.

PMID- 23963695
TI  - The diaphoretic hand.

PMID- 23963694
TI  - A review of the toxicity of HIV medications.
AB  - Antiretroviral therapy has changed human immunodeficiency virus (HIV) infection
      from a near-certainly fatal illness to one that can be managed chronically. More
      patients are taking antiretroviral drugs (ARVs) for longer periods of time, which
      naturally results in more observed toxicity. Overdose with ARVs is not commonly
      reported. The most serious overdose outcomes have been reported in neonates who
      were inadvertently administered supratherapeutic doses of HIV prophylaxis
      medications. Typical ARV regimens include a "backbone" of two nucleoside reverse
      transcriptase inhibitors (NRTI) and a "base" of either a protease inhibitor (PI)
      or nonnucleoside reverse transcriptase inhibitor. New classes of drugs called
      entry inhibitors and integrase inhibitors have also emerged. Older NRTIs were
      associated with mitochondrial toxicity, but this is less common in the newer
      drugs, emtricitabine, lamivudine, and tenofovir. Mitochondrial toxicity results
      from NRTI inhibition of a mitochondrial DNA polymerase. Mitochondrial toxicity
      manifests as myopathy, neuropathy, hepatic failure, and lactic acidosis. Routine
      lactate assessment in asymptomatic patients is not indicated. Lactate
      concentration should be obtained in patients taking NRTIs who have fatigue,
      nausea, vomiting, or vague abdominal pain. Mitochondrial toxicity can be fatal
      and is treated by supportive care and discontinuing NRTIs. Metabolic cofactors
      like thiamine, carnitine, and riboflavin may be helpful in managing mitochondrial
      toxicity. Lipodystrophy describes changes in fat distribution and lipid
      metabolism that have been attributed to both PIs and NRTIs. Lipodystrophy
      consists of loss of fat around the face (lipoatrophy), increase in truncal fat,
      and hypertriglyceridemia. There is no specific treatment of lipodystrophy.
      Clinicians should be able to recognize effects of chronic toxicity of ARVs,
      especially mitochondrial toxicity. 

PMID- 23963696
TI  - miR-146a-5p circuitry uncouples cell proliferation and migration, but not
      differentiation, in human mesenchymal stem cells.
AB  - Administration of mesenchymal stem cells (MSCs) has the potential to ameliorate
      degenerative disorders and to repair damaged tissues. The homing of transplanted
      MSCs to injured sites is a critical property of engraftment. Our aim was to
      identify microRNAs involved in controlling MSC proliferation and migration. MSCs
      can be isolated from bone marrow and umbilical cord Wharton's jelly (BM-MSCs and
      WJ-MSCs, respectively), and WJ-MSCs show poorer motility yet have a better
      amplification rate compared with BM-MSCs. Small RNA sequencing revealed that miR
      146a-5p is significantly overexpressed and has high abundance in WJ-MSCs.
      Knockdown of miR-146a-5p in WJ-MSCs inhibited their proliferation yet enhanced
      their migration, whereas overexpression of miR-146a-5p in BM-MSCs did not
      influence their osteogenic and adipogenic potentials. Chemokine (C-X-C motif)
      ligand 12 (CXCL12), together with SIKE1, which is an I-kappa-B kinase epsilon
      (IKKepsilon) suppressor, is a direct target of miR-146a-5p in MSCs. Knockdown of
      miR-146a-5p resulted in the down-regulation of nuclear factor kappa-B (NF-kappaB)
      activity, which is highly activated in WJ-MSCs and is known to activate miR-146a
      5p promoter. miR-146a-5p is also downstream of CXCL12, and a negative feedback
      loop is therefore formed in MSCs. These findings suggest that miR-146a-5p is
      critical to the uncoupling of motility and proliferation of MSCs. Our miRNome
      data also provide a roadmap for further understanding MSC biology. 

PMID- 23963697
TI  - Mediator is an intrinsic component of the basal RNA polymerase II machinery in
      vivo.
AB  - Mediator is a prominent multisubunit coactivator that functions as a bridge
      between gene-specific activators and the basal RNA polymerase (Pol) II initiation
      machinery. Here, we study the poorly documented role of Mediator in basal, or
      activator-independent, transcription in vivo. We show that Mediator is still
      present at the promoter when the Pol II machinery is recruited in the absence of
      an activator, in this case through a direct fusion between a basal transcription
      factor and a heterologous DNA binding protein bound to the promoter. Moreover,
      transcription resulting from activator-independent recruitment of the Pol II
      machinery is impaired by inactivation of the essential Mediator subunit Med17 due
      to the loss of Pol II from the promoter. Our results strongly support that
      Mediator is an integral component of the minimal machinery essential in vivo for
      stable Pol II association with the promoter. 

PMID- 23963698
TI  - Crystal structures of B-DNA dodecamer containing the epigenetic modifications 5
      hydroxymethylcytosine or 5-methylcytosine.
AB  - 5-Hydroxymethylcytosine (5-hmC) was recently identified as a relatively frequent
      base in eukaryotic genomes. Its physiological function is still unclear, but it
      is supposed to serve as an intermediate in DNA de novo demethylation. Using X-ray
      diffraction, we solved five structures of four variants of the d(CGCGAATTCGCG)
      dodecamer, containing either 5-hmC or 5-methylcytosine (5-mC) at position 3 or at
      position 9. The observed resolutions were between 1.42 and 1.99 A. Cytosine
      modification in all cases influences neither the whole B-DNA double helix
      structure nor the modified base pair geometry. The additional hydroxyl group of 5
      hmC with rotational freedom along the C5-C5A bond is preferentially oriented in
      the 3' direction. A comparison of thermodynamic properties of the dodecamers
      shows no effect of 5-mC modification and a sequence-dependent only slight
      destabilizing effect of 5-hmC modification. Also taking into account the results
      of a previous functional study [Munzel et al. (2011) (Improved synthesis and
      mutagenicity of oligonucleotides containing 5-hydroxymethylcytosine, 5
      formylcytosine and 5-carboxylcytosine. Chem. Eur. J., 17, 13782-13788)], we
      conclude that the 5 position of cytosine is an ideal place to encode epigenetic
      information. Like this, neither the helical structure nor the thermodynamics are
      changed, and polymerases cannot distinguish 5-hmC and 5-mC from unmodified
      cytosine, all these effects are making the former ones non-mutagenic. 

PMID- 23963699
TI  - In situ visualization of telomere elongation patterns in human cells.
AB  - The telomerase enzyme plays a critical role in human aging and cancer biology by
      maintaining telomere length and extending the proliferative lifespan of most stem
      cells and cancer cells. Despite the importance of this enzyme, our understanding
      of the mechanisms that regulate its activity and establish telomere length
      homeostasis in mammalian cells is incomplete, in part because the perfect
      repetitive nature of telomeric sequence hampers in situ detection of telomere
      elongation patterns. Here, we describe a novel assay using a mutant telomerase
      that adds a well-tolerated variant telomeric repeat sequence to telomere ends. By
      specifically detecting the addition of these variant repeats, we can directly
      visualize telomere elongation events in human cells. We validate this approach by
      in situ mapping of telomere elongation patterns within individual nuclei and
      across a population of cells. 

PMID- 23963700
TI  - Replisome stall events have shaped the distribution of replication origins in the
      genomes of yeasts.
AB  - During S phase, the entire genome must be precisely duplicated, with no sections
      of DNA left unreplicated. Here, we develop a simple mathematical model to
      describe the probability of replication failing due to the irreversible stalling
      of replication forks. We show that the probability of complete genome replication
      is maximized if replication origins are evenly spaced, the largest inter-origin
      distances are minimized, and the end-most origins are positioned close to
      chromosome ends. We show that origin positions in the yeast Saccharomyces
      cerevisiae genome conform to all three predictions thereby maximizing the
      probability of complete replication if replication forks stall. Origin positions
      in four other yeasts-Kluyveromyces lactis, Lachancea kluyveri, Lachancea waltii
      and Schizosaccharomyces pombe-also conform to these predictions. Equating failure
      rates at chromosome ends with those in chromosome interiors gives a mean per
      nucleotide fork stall rate of ~5 * 10(-8), which is consistent with experimental
      estimates. Using this value in our theoretical predictions gives replication
      failure rates that are consistent with data from replication origin knockout
      experiments. Our theory also predicts that significantly larger genomes, such as
      those of mammals, will experience a much greater probability of replication
      failure genome-wide, and therefore will likely require additional compensatory
      mechanisms. 

PMID- 23963701
TI  - Increasing cleavage specificity and activity of restriction endonuclease KpnI.
AB  - Restriction enzyme KpnI is a HNH superfamily endonuclease requiring divalent
      metal ions for DNA cleavage but not for binding. The active site of KpnI can
      accommodate metal ions of different atomic radii for DNA cleavage. Although
      Mg(2+) ion higher than 500 MUM mediates promiscuous activity, Ca(2+) suppresses
      the promiscuity and induces high cleavage fidelity. Here, we report that a
      conservative mutation of the metal-coordinating residue D148 to Glu results in
      the elimination of the Ca(2+)-mediated cleavage but imparting high cleavage
      fidelity with Mg(2+). High cleavage fidelity of the mutant D148E is achieved
      through better discrimination of the target site at the binding and cleavage
      steps. Biochemical experiments and molecular dynamics simulations suggest that
      the mutation inhibits Ca(2+)-mediated cleavage activity by altering the geometry
      of the Ca(2+)-bound HNH active site. Although the D148E mutant reduces the
      specific activity of the enzyme, we identified a suppressor mutation that
      increases the turnover rate to restore the specific activity of the high fidelity
      mutant to the wild-type level. Our results show that active site plasticity in
      coordinating different metal ions is related to KpnI promiscuous activity, and
      tinkering the metal ion coordination is a plausible way to reduce promiscuous
      activity of metalloenzymes. 

PMID- 23963702
TI  - Rational design of antisense oligonucleotides targeting single nucleotide
      polymorphisms for potent and allele selective suppression of mutant Huntingtin in
      the CNS.
AB  - Autosomal dominant diseases such as Huntington's disease (HD) are caused by a
      gain of function mutant protein and/or RNA. An ideal treatment for these diseases
      is to selectively suppress expression of the mutant allele while preserving
      expression of the wild-type variant. RNase H active antisense oligonucleotides
      (ASOs) or small interfering RNAs can achieve allele selective suppression of gene
      expression by targeting single nucleotide polymorphisms (SNPs) associated with
      the repeat expansion. ASOs have been previously shown to discriminate single
      nucleotide changes in targeted RNAs with ~5-fold selectivity. Based on RNase H
      enzymology, we enhanced single nucleotide discrimination by positional
      incorporation of chemical modifications within the oligonucleotide to limit RNase
      H cleavage of the non-targeted transcript. The resulting oligonucleotides
      demonstrate >100-fold discrimination for a single nucleotide change at an SNP
      site in the disease causing huntingtin mRNA, in patient cells and in a completely
      humanized mouse model of HD. The modified ASOs were also well tolerated after
      injection into the central nervous system of wild-type animals, suggesting that
      their tolerability profile is suitable for advancement as potential allele
      selective HD therapeutics. Our findings lay the foundation for efficient allele
      selective downregulation of gene expression using ASOs-an outcome with broad
      application to HD and other dominant genetic disorders. 

PMID- 23963703
TI  - High frequency of adverse local tissue reactions in asymptomatic patients with
      metal-on-metal THA.
AB  - BACKGROUND: The key to successful management of patients with metal-on-metal
      (MOM) THAs is to diagnose adverse local tissue reactions (ALTRs) early. ALTRs
      have been described in asymptomatic patients with resurfacing arthroplasties.
      Whether this concerning finding applies to modular MOM THAs is unknown.
      QUESTIONS/PURPOSES: We (1) determined the prevalence of ALTRs in asymptomatic
      patients with modular MOM THAs, (2) described any differences in the appearance
      of these lesions between symptomatic and asymptomatic patients, and (3) analyzed
      potential predictive factors for any associations with ALTR prevalence. METHODS:
      We evaluated 114 patients with modular MOM THAs who had MRI with metal artifact
      reduction sequence software and metal ion laboratory results at a mean of 57
      months postoperatively. There were 83 asymptomatic and 31 symptomatic patients.
      We defined ALTRs as abnormal fluid collections, solid or semisolid pseudotumors,
      or muscle or bone damage. Ion levels, lesion size, and cup abduction angles were
      analyzed. RESULTS: Twenty-six (31%) asymptomatic patients had ALTR lesions, all
      of which were in the greater trochanteric area. Most lesions in symptomatic
      patients also were in that location, but there was more diversity of location in
      this group. The cup position among patients with ALTRs was generally good; the
      average abduction angle for the asymptomatic patients with ALTRs was 40 degrees .
      In 24 (92%) and 22 (85%) of 26 asymptomatic patients with ALTRs, respectively,
      chromium and cobalt levels were below the 7-ppb threshold. CONCLUSIONS: A 31%
      incidence of periarticular fluid collections in asymptomatic patients with
      modular MOM THAs is alarming and calls into question any algorithmic approach
      dependent on symptomatology. The presence of pain was insufficient to identify
      patients at risk for ALTRs. To determine whether routine cross-sectional imaging
      of all asymptomatic patients with MOM implants is necessary will require a larger
      study cohort, longer followup, and clearer understanding of the natural history
      of periarticular lesions in these patients.

PMID- 23963704
TI  - Does the direct anterior approach in THA offer faster rehabilitation and
      comparable safety to the posterior approach?
AB  - BACKGROUND: Newer surgical approaches to THA, such as the direct anterior
      approach, may influence a patient's time to recovery, but it is important to make
      sure that these approaches do not compromise reconstructive safety or accuracy.
      QUESTIONS/PURPOSES: We compared the direct anterior approach and conventional
      posterior approach in terms of (1) recovery of hip function after primary THA,
      (2) general health outcomes, (3) operative time and surgical complications, and
      (4) accuracy of component placement. METHODS: In this prospective, comparative,
      nonrandomized study of 120 patients (60 direct anterior THA, 60 posterior THAs),
      we assessed functional recovery using the VAS pain score, timed up and go (TUG)
      test, motor component of the Functional Independence MeasureTM (M-FIMTM), UCLA
      activity score, Harris hip score, and patient-maintained subjective milestone
      diary and general health outcome using SF-12 scores. Operative time,
      complications, and component placement were also compared. RESULTS: Functional
      recovery was faster in patients with the direct anterior approach on the basis of
      TUG and M-FIMTM up to 2 weeks; no differences were found in terms of the other
      metrics we used, and no differences were observed between groups beyond 6 weeks.
      General health outcomes, operative time, and complications were similar between
      groups. No clinically important differences were observed in terms of implant
      alignment. CONCLUSIONS: We observed very modest functional advantages early in
      recovery after direct anterior THA compared to posterior-approach THA. Randomized
      trials are needed to validate these findings, and these findings may not
      generalize well to lower-volume practice settings or to surgeons earlier in the
      learning curve of direct anterior THA.

PMID- 23963705
TI  - Dry powder antibiotic aerosol product development: inhaled therapy for
      tuberculosis.
AB  - Inhaled therapies offer a unique approach to the treatment of tuberculosis (TB)
      using a relevant target organ system as a route of administration. The number of
      research reports on this topic has been increasing exponentially in the last
      decade but studies of clinical efficacy have been rare in recent times. The
      challenge is to take many research findings and translate them into a strategy
      for product development. Dry powder inhalers are the dominant drug product under
      consideration by those interested in the inhaled therapy for TB. A range of
      factors including candidate drug, formulation, device selection, drug product
      testing for proof of concept, and preclinical and clinical purposes all demand
      different considerations. The following review is intended to raise awareness of
      a growing body of evidence, suggesting that inhaled therapy for TB is possible
      and desirable. In addition, it is intended to outline key elements of the product
      development activity for this particular application that has not been discussed
      elsewhere in the literature. Hopefully, this will encourage those with
      development expertise to seriously contemplate the steps required to bring such
      products forward.

PMID- 23963707
TI  - Neurocognitive disorders in sentenced male offenders: implications for
      rehabilitation.
AB  - BACKGROUND: Neurocognitive deficits are frequent among male offenders and tend to
      be associated with a more serious risk of anti-social activity, but they are not
      systematically allowed for in rehabilitation programmes. AIM: The aim of this
      study was to evaluate neurocognitive performance in a sample of sentenced Finnish
      male prisoners and consider the implications for prison programme entry. METHODS:
      Seventy-five sentenced male prisoners were examined using a neurocognitive test
      battery. RESULTS: Depending on the neurocognitive domain, from 5% to 49% of the
      men demonstrated marked neurocognitive deficits in tests of motor dexterity,
      visuospatial/construction skills, verbal comprehension, verbal and visual memory
      and attention shift. Verbal IQ was more impaired than performance IQ. There was
      no association between most serious offence type and neurocognitive performance,
      but correlations between attention deficit indices and number of previous
      convictions suggested that recidivists may have an attention disorder profile.
      Cluster analysis identified two subgroups of offenders, separated by very poor or
      merely poor cognitive performance. Motor dexterity, visuo-construction and verbal
      memory deficits were not wholly explained by lower IQ measures. CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: Our sample was small, but the nature and extent of the
      neurocognitive deficits found suggest that wider use of neurocognitive
      assessments, which the men generally tolerated well, could help select those most
      likely to need offender programmes and that the effectiveness of these may be
      enhanced by some specific cognitive remediation before progressing to more
      complex social tasks.

PMID- 23963706
TI  - Dietary grape seed extract ameliorates symptoms of inflammatory bowel disease in
      IL10-deficient mice.
AB  - Grape seed extract (GSE) is a by-product of the wine industry, with abundant
      polyphenolic compounds known for their anti-inflammatory and anti-oxidative
      effects. Using IL10-deficient mice (IL10KO), here we showed that GSE (1% of dry
      feed weight) ameliorated inflammatory bowel disease indices, increased colonic
      goblet cell numbers and decreased myeloperoxidase levels in the large intestine.
      Concomitantly, GSE supplementation attenuated inflammation, decreased the
      expression of pore forming tight junction protein claudin2, and increased levels
      of Lactobacilli and Bacteroides in the gut microbiota of IL10KO mice. In summary,
      our study shows that GSE has protective roles on inflammatory bowel disease
      through altering gut inflammation, tight junction protein expression, and gut
      microbiota composition. 

PMID- 23963708
TI  - Prenatal exposure to persistent organic pollutants and rapid weight gain and
      overweight in infancy.
AB  - OBJECTIVE: To examine the effects of prenatal exposure to persistent organic
      pollutants (POPs) on rapid growth in the first 6 months of life and overweight at
      14 months of age. DESIGN AND METHODS: In a Spanish birth cohort study, the POPs
      dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), and
      polychlorinated biphenyls (PCBs-congeners 153, 138, 180) were measured in
      maternal serum collected in the first trimester of pregnancy during 2003-2008.
      Rapid growth was defined as a z-score weight gain >0.67 SD between 6 months of
      age and birth. Overweight at 14 months was defined as a BMI z-score >=85th
      percentile. Generalized linear models examined the association between POPs and
      rapid growth (N = 1285) and overweight (N = 1198). RESULTS: The analysis
      population included 24% rapid growers and 30% overweight infants. DDE and HCB
      were positively associated with rapid growth and with overweight. There was some
      indication that infant sex and exclusive breastfeeding duration may modify the
      effects of DDE, and that maternal prepregnancy BMI status may influence the
      effects of HCB. PCBs were not related to postnatal growth. CONCLUSION: Prenatal
      exposure to DDE and HCB may be associated with early postnatal growth. Further
      research is needed to evaluate the persistence of these associations at older
      ages.

PMID- 23963709
TI  - Neural stem cells grafts decrease neural apoptosis associated with caspase-7
      downregulation and BDNF upregulation in rats following spinal cord hemisection.
AB  - Transplantation of neural stem cells (NSCs) into lesioned spinal cord
      demonstrated a beneficial effect for neural repair, the underlying mechanism,
      however, remains to be elusive. Here, we showed that NSCs, possessing the
      capacity to differentiate toward into neurons and astrocytes, exhibit a
      neuroprotective effect by anti-apoptosis mechanism in spinal cord hemi-transected
      rats despite it did not improve behavior. Intravenous NSCs injection
      substantially upregulated the level of BDNF mRNA but not its receptor TrkB in
      hemisected spinal cord, while caspase-7, a downstream apoptosis gene of caspase
      3, has been largely down-regulated. TUNEL staining showed that the number of
      apoptosis cells in injured spinal cord decreased significantly, compared with
      seen in rats with no NSCs administration. The present finding therefore provided
      crucial evidence to explain neuroprotective effect of NSCs grafts in hemisected
      spinal cord, which is associated with BDNF upregulation and caspase-7
      downregulation. 

PMID- 23963710
TI  - Psychosocial support for children and families requiring renal replacement
      therapy.
AB  - Chronic kidney disease (CKD) and the need for renal replacement therapy (RRT) can
      place a great strain on the child and family. As well as the medical and
      nutritional prescription, each child and family requires an individual
      psychosocial prescription that requires input from multiprofessional team
      members. The information needs of each child and family need to be constantly
      evaluated as well as the choice of therapy in relation to social, psychological
      and economic factors. Many tertiary units lack adequate "time" to deliver such
      assessments and coordinate the support and respite care for those on long-term
      dialysis, especially when significant numbers of children are now accepted onto
      RRT programmes with co-morbidities. National and international standards are
      needed for the staffing of comprehensive tertiary paediatric renal units as well
      as studies evaluating supportive care to families. 

PMID- 23963711
TI  - Partial proteasome inhibitors induce hair follicle growth by stabilizing beta
      catenin.
AB  - The activation of tissue stem cells from their quiescent state represents the
      initial step in the complex process of organ regeneration and tissue repair.
      While the identity and location of tissue stem cells are becoming known, how key
      regulators control the balance of activation and quiescence remains mysterious.
      The vertebrate hair is an ideal model system where hair cycling between growth
      and resting phases is precisely regulated by morphogen signaling pathways, but
      how these events are coordinated to promote orderly signaling in a spatial and
      temporal manner remains unclear. Here, we show that hair cycle timing depends on
      regulated stability of signaling substrates by the ubiquitin-proteasome system.
      Topical application of partial proteasomal inhibitors (PaPIs) inhibits epidermal
      and dermal proteasome activity throughout the hair cycle. PaPIs prevent the
      destruction of the key anagen signal beta-catenin, resulting in more rapid hair
      growth and dramatically shortened telogen. We show that PaPIs induce excess beta
      catenin, act similarly to the GSK3beta antagonist LiCl, and antagonize Dickopf
      related protein-mediated inhibition of anagen. PaPIs thus represent a novel class
      of hair growth agents that act through transiently modifying the balance of stem
      cell activation and quiescence pathways.

PMID- 23963712
TI  - Probiotics for treating persistent diarrhoea in children.
AB  - BACKGROUND: Persistent diarrhoea (diarrhoea lasting more than 14 days) accounts
      for one third of all diarrhoea related deaths in developing countries in some
      studies. Probiotics may help treatment. OBJECTIVES: To evaluate probiotics for
      treating persistent diarrhoea in children. SEARCH METHODS: We searched the
      Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE,
      EMBASE, and LILACS. We also contacted authors of included trials and
      organizations working in the field, and checked reference lists. The date of the
      most recent search was 13 December 2012 SELECTION CRITERIA: Randomized controlled
      trials comparing a specified probiotic agent with placebo or no probiotic in
      children with persistent diarrhoea. DATA COLLECTION AND ANALYSIS: Two review
      authors assessed the eligibility, risk of bias, extracted and analysed data.
      Differences were resolved by discussion. Statistical analysis were performed
      using the fixed-effect model and the results were expressed as mean difference
      (MD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS:
      Four trials were included, with a total number of 464 participants; one trial had
      a low risk of bias. Meta-analysis showed that probiotics reduced the duration of
      persistent diarrhoea (mean difference 4.02 days, 95% CI 4.61 to 3.43 days, n =
      324, two trials). Stool frequency was reduced with probiotics in two trials. One
      trial reported a shorter hospital stay, which was significant, but numbers were
      small. No adverse events were reported. AUTHORS' CONCLUSIONS: There is limited
      evidence suggesting probiotics may be effective in treating persistent diarrhoea
      in children.

PMID- 23963713
TI  - Density functional study of bare gold clusters: the ten-vertex neutral system.
AB  - Four novel Au10 structures have been located by means of density functional
      methods and their geometry and electronic structure are discussed. Furthermore,
      the behavior of less extensive basis sets in conjunction with the B3PW91
      functional is compared to a highly accurate and more extensive energy-consistent
      scalar-relativistic pseudopotential and basis set for neutral ten-vertex gold
      clusters. The values obtained for several structural parameters for known and
      novel optimized Au10 systems are discussed. 

PMID- 23963714
TI  - Frequency dependence of lung volume changes during superimposed high-frequency
      jet ventilation and high-frequency jet ventilation.
AB  - BACKGROUND: Superimposed high-frequency jet ventilation (SHFJV) has proved to be
      safe and effective in clinical practice. However, it is unclear which frequency
      range optimizes ventilation and gas exchange. The aim of this study was to
      systematically compare high-frequency jet ventilation (HFJV) with HFJV by
      assessing chest wall volume variations (DeltaEEV(CW)) and gas exchange in
      relation to variable high frequency. METHODS: SHFJV or HFJV were used
      alternatively to ventilate the lungs of 10 anaesthetized pigs (21-25 kg). The low
      frequency component was kept at 16 min(-1) in SHFJV. In both modes, high
      frequencies ranging from 100 to 1000 min(-1) were applied in random order and
      ventilation was maintained for 5 min in all modalities. Chest wall volume
      variations were obtained using opto-electronic plethysmography. Airway pressures
      and arterial blood gases were measured repeatedly. RESULTS: SHFJV increased
      DeltaEEV(CW) compared with HFJV; the difference ranged from 43 to 68 ml. Tidal
      volume (V(T)) was always >240 ml during SHFJV whereas during HFJV ranged from 92
      ml at the ventilation frequency of 100 min(-1) to negligible values at
      frequencies >300 min(-1). We observed similar patterns for Pa(O2) and Pa(CO2).
      SHFJV provided generally higher, frequency-independent oxygenation (Pa(O2) at
      least 32.0 kPa) and CO2 removal (Pa(CO2) ~5.5 kPa), whereas HFJV led to hypoxia
      and hypercarbia at higher rates (Pa(O2) <10 kPa and Pa(CO2)>10 kPa at f(HF)>300
      min(-1)). CONCLUSIONS: In a porcine model, SHFJV was more effective in increasing
      end-expiratory volume than single-frequency HFJV, but both modes may provide
      adequate ventilation in the absence of airway obstruction and respiratory
      disease, except for HFJV at frequencies >=300 min(-1).

PMID- 23963715
TI  - Partial oxidative conversion of methane to methanol through selective inhibition
      of methanol dehydrogenase in methanotrophic consortium from landfill cover soil.
AB  - Using a methanotrophic consortium (that includes Methylosinus sporium NCIMB
      11126, Methylosinus trichosporium OB3b, and Methylococcus capsulatus Bath)
      isolated from a landfill site, the potential for partial oxidation of methane
      into methanol through selective inhibition of methanol dehydrogenase (MDH) over
      soluble methane monooxygenase (sMMO) with some selected MDH inhibitors at varied
      concentration range, was evaluated in batch serum bottle and bioreactor
      experiments. Our result suggests that MDH activity could effectively be inhibited
      either at 40 mM of phosphate, 100 mM of NaCl, 40 mM of NH4Cl or 50 MUM of EDTA
      with conversion ratios (moles of CH3OH produced per mole CH4 consumed) of 58, 80,
      80, and 43 %, respectively. The difference between extent of inhibition in MDH
      activity and sMMO activity was significantly correlated (n = 6, p < 0.05) with
      resultant methane to methanol conversion ratio. In bioreactor study with 100 mM
      of NaCl, a maximum specific methanol production rate of 9 MUmol/mg h was
      detected. A further insight with qPCR analysis of MDH and sMMO coding genes
      revealed that the gene copy number continued to increase along with biomass
      during reactor operation irrespective of presence or absence of inhibitor, and
      differential inhibition among two enzymes was rather the key for methanol
      production. 

PMID- 23963716
TI  - Enzymatic degradation of monocrotophos by extracellular fungal OP hydrolases.
AB  - The present study explores the potential of extracellular fungal organophosphate
      (OP) hydrolase for the degradation of monocrotophos. Extracellular OP hydrolases
      were isolated and purified from five different fungal isolates viz. Aspergillus
      niger (M1), Aspergillus flavus (M2), Penicillium aculeatum (M3), Fusarium
      pallidoroseum (M4), and Macrophomina sp. (M5) by AmSO4 precipitation, dialysis,
      and G-100 chromatography. M3 showed highest percentage yield of 68.81 followed by
      55.41 % for M1. Each of the purified enzyme fraction constituted of two different
      subunits of 33- and 67-kDa molecular weight. Optimum enzyme fraction (150 MUg ml(
      1)) rapidly degraded monocrotophos within 120 h in phosphorus-free liquid culture
      medium (CZM) with K deg of 0.0368, 0.0138, 0.048, 0.016, 0.0138, and 0.048 day(
      1) and half-life of 0.79, 2.11, 0.6, 1.8, and 2.11 days for M1, M2, M3, M4, and
      M5, respectively. The results were further confirmed by high performance thin
      layer chromatography and Fourier transform infrared which indicate the
      disappearance of monocrotophos by hydrolytic cleavage of vinyl phosphate bond.
      The overall order of enzymatic degradation was found to be P. aculeatum > A.
      niger > F. pallidoroseum > A. flavus = Macrophomina sp. Hence, the study
      concludes that extracellular OP hydrolases efficiently degraded monocrotophos and
      could be used as a potential candidate for the detoxification of this neurotoxin
      pesticide. 

PMID- 23963717
TI  - Effect of phosphate on glucosamine production by ethanolic fungus Mucor indicus.
AB  - In this study, the effect of phosphorous compound concentration on the production
      of glucosamine by Mucor indicus was investigated. Changes in the yield of
      ethanol, the major metabolite of the fungus, were also followed besides. The
      alkali insoluble material of the biomass of the fungus mainly contained
      phosphates and polymers of glucosamine and N-acetyl glucosamine, i.e., chitin and
      chitosan. Yields of glucosamine (78-113 g/kg dry fungal biomass) and ethanol (200
      370 g/kg glucose) were significantly affected by the phosphorous concentration.
      The results showed that lower concentrations of phosphorous favored the
      production of glucosamine while higher ethanol as well as biomass yields was
      obtained at higher concentrations. The best concentration was 0.5 g/l where
      glucosamine yield was 0.37 g/l (11 % of the biomass). At this phosphate
      concentration, ethanol and biomass yields were 360 and 76 g/kg glucose,
      respectively. On average, proteins comprised 51.5 % of the biomass. Glycerol was
      the second important metabolite during the fermentation by the fungus which
      appeared at lower yields (20-34 g/kg glucose). 

PMID- 23963718
TI  - Response of human mesenchymal stem cells to patterned and randomly oriented
      poly(vinyl alcohol) nano-fibrous scaffolds surface-modified with Arg-Gly-Asp
      (RGD) ligand.
AB  - The aim of this study was to obtain a better insight of how nano-fibrous
      scaffolds can affect human mesenchymal stem cells responses. Therefore, in this
      study, using electrospinning technique, poly(vinyl alcohol) (PVA) nano-fibers
      with two different patterns were prepared. In the first structure, PVA nano
      fibers were oriented randomly and in the second structure, nano-fibers were
      electrospun in such a way that a special pattern was obtained. In order to
      enhance their stability, scaffolds were cross-linked using glutaraldehyde vapor.
      RGD immobilization was used to improve cell adhesion properties of the scaffolds.
      SEM micrographs demonstrated that the cell adhesion was effectively enhanced
      after RGD immobilization and higher cell densities were observed on RGD-modified
      scaffolds. Randomly oriented nano-fibers showed better cell adhesion compared to
      patterned structure. Patterned structure also revealed slightly lower cell
      viability compared to random nano-fibers. Finally, it was assumed that randomly
      oriented nano-fibers provide a more favorable surface for cells. 

PMID- 23963719
TI  - Green synthesis and characterization of hybrid collagen-cellulose-albumin
      biofibers from skin waste.
AB  - Collagen (C) and cellulose are prominent biopolymers from the animal and plant
      kingdom and widely used in bioengineering. Albumin, on the other hand, is the
      most abundant plasma protein present in mammalian blood. In this work, collagen
      extracted from animal skin waste was blended with hydroxyethyl cellulose (HEC)
      and bovine serum albumin (A) and wet-spun to form hybrid biodegradable C/HEC/A
      fibers. They were further cross-linked with glutaraldehyde vapors and analyzed. X
      ray diffraction and infra-red spectroscopic studies of the hybrid fibers display
      peaks corresponding to collagen, cellulose, and albumin. Incorporation of
      cellulose into the biopolymeric matrix leads to a reasonable improvement in
      mechanical, swelling, and thermal properties of hybrid fibers. Addition of
      albumin improves the regularity of fiber surface without altering the porosity as
      observed under a microscope. Hence, the formed hybrid biofibers can be
      potentially used as a suture material as well as for different biomedical
      applications due to their improved properties. 

PMID- 23963720
TI  - Hyperhomocysteinemia in patients with pulmonary embolism is associated with
      impaired plasma fibrinolytic capacity.
AB  - Hyperhomocysteinemia (HHcy) affects haemostasis and shifts its balance in favour
      of thrombosis. In vitro and in vivo studies suggested that HHcy may impair
      fibrinolysis either by influencing the plasma levels of fibrinolytic factors or
      by altering the fibrinogen structure. We investigated the influence of mild HHcy
      levels on plasma fibrinolytic potential by using clot lysis time (CLT) and fibrin
      susceptibility to plasmin-induced lysis in 94 patients with previous pulmonary
      embolism and no pulmonary hypertension. CLT was measured as lysis time of tissue
      factor induced clots exposed to exogenous tissue plasminogen activator (t-PA).
      The rate of in vitro plasmin-mediated cleavage of fibrin beta-chain was assessed
      over a 6-h period on fibrin clots, which were obtained by exposition to thrombin
      of purified fibrinogen. Homocysteine plasma levels were measured by Abbott Imx
      immunoassay and we considered as altered the values above 15 MUmol/L according to
      the literature. In 68 patients homocysteine levels were below 15 MUmol/L (NHcy)
      and in 26 they were above (HHcy). Significant differences were observed between
      the two groups regarding plasma fibrinolytic potential (p = 0.016), TAFIact
      (expressed as clot lysis ratio) (p = 0.02), t-PA (0.008) and PLG (0.037), but not
      for the other assessed components. The HHcy-patients had a threefold higher risk
      to have an impaired fibrinolysis. Instead, a multivariate logistic regression
      analysis adjusted for significances of univariate showed that HHcy (OR 5.2 95% CI
      1.7-15.9; p = 0.003) and BMI (OR 5.0 95% CI 1.6-15.9; p = 0.006) resulted
      independently associated with impaired fibrinolytic activity. HHcy affects TAFI
      mediated hypofibrinolysis but not fibrin(ogen) structure or function as
      documented by fibrin degradation analysis.

PMID- 23963721
TI  - Utility of computer-assisted approaches for population surveillance of physical
      activity.
AB  - BACKGROUND: Computer-assisted techniques may be a useful way to enhance physical
      activity surveillance and increase accuracy of reported behaviors. PURPOSE:
      Evaluate the reliability and validity of a physical activity (PA) self-report
      instrument administered by telephone and internet. METHODS: The telephone
      administered Active Australia Survey was adapted into 2 forms for internet self
      administration: survey questions only (internet-text) and with videos
      demonstrating intensity (internet-video). Data were collected from 158 adults (20
      69 years, 61% female) assigned to telephone (telephone-interview) (n = 56),
      internet-text (n = 51), or internet-video (n = 51). Participants wore an
      accelerometer and completed a logbook for 7 days. Test-retest reliability was
      assessed using intraclass correlation coefficients (ICC). Convergent validity was
      assessed using Spearman correlations. RESULTS: Strong test-retest reliability was
      observed for PA variables in the internet-text (ICC = 0.69 to 0.88), internet
      video (ICC = 0.66 to 0.79), and telephone-interview (ICC = 0.69 to 0.92) groups
      (P-values < 0.001). For total PA, correlations (rho) between the survey and
      Actigraph+logbook were rho = 0.47 for the internet-text group, rho = 0.57 for the
      internet-video group, and rho = 0.65 for the telephone-interview group. For
      vigorous-intensity activity, the correlations between the survey and
      Actigraph+logbook were 0.52 for internet-text, 0.57 for internet-video, and 0.65
      for telephone-interview (P < .05). CONCLUSIONS: Internet-video of the survey had
      similar test-retest reliability and convergent validity when compared with the
      telephone-interview, and should continue to be developed.

PMID- 23963723
TI  - 4D Non-uniformly sampled C,C-NOESY experiment for sequential assignment of 13C,
      15N-labeled RNAs.
AB  - A 4D (13)C(aromatic),(13)C(ribose)-edited NOESY experiment is introduced to
      improve sequential assignment of non-coding RNA, often hampered by a limited
      dispersion of (1)H and (13)C chemical shifts. The (13)C-labeling of RNA is fully
      utilized by inclusion of two (13)C evolution periods. These dimensions provide
      enhanced dispersion of resonances in the 4D spectrum. High spectral resolution is
      obtained using random non-uniform sampling in three indirect dimensions. The
      autocorrelation peaks are efficiently suppressed using band-selective pulses.
      Since the dynamic range of observed resonances is significantly decreased, the
      reconstruction of the 4D spectrum is greatly simplified. The experiment can
      replace two conventionally sampled 3D NOESY spectra (either ribose-(13)C- or
      aromatic-(13)C-separated), and remove most ambiguities encountered during
      sequential walks. The assignment strategy based on a homonuclear and 4D C,C
      edited NOESY experiments is proposed and verified on a 34-nt RNA showing typical
      structure elements. 

PMID- 23963724
TI  - Attitudes and knowledge of primary care physicians regarding prostate cancer
      screening.
AB  - Recently, several prospective randomized prostate cancer screening studies have
      been reported. We report the results of a questionnaire administered to primary
      care physicians (PCPs) to determine their attitudes on prostate cancer screening
      and compared these results to those obtained when the same questionnaire was
      administered to a different large cohort of PCPs in 2006 prior to the reporting
      of these randomized studies. A 24-item questionnaire designed to assess prostate
      cancer knowledge and screening attitudes was administered to PCPs within central
      Florida and those PCPs attending a state conference. Completed surveys were
      returned and analyzed. All reported p values were two-sided, and those p values
      less than 0.05 were considered to be statistically significant. Seven hundred and
      eighty PCPs received the study questionnaire, and 168 (22 %) PCPs returned the
      completed questionnaire. Sixty-eight percent of responders stated that they
      recommend prostate cancer screening to >75 % of their patients over the age of 50
      years, up from 47 % in 2006 (p < 0.001). Seventy-four percent of responders felt
      screening was effective. The overall mean score of the knowledge survey was 66 %,
      which was similar to the cohort from 2006. Knowledge scores were not associated
      with screening attitudes and behaviors. On multivariate analysis, practice
      setting and percentage of Medicaid patients in the practice were associated with
      attitude scores. Our current findings imply that despite the recent landmark
      studies published on prostate cancer screening, PCPs' screening attitudes have
      changed minimally over the past 5 years.

PMID- 23963722
TI  - Determination of structural topology of a membrane protein in lipid bilayers
      using polarization optimized experiments (POE) for static and MAS solid state NMR
      spectroscopy.
AB  - The low sensitivity inherent to both the static and magic angle spinning
      techniques of solid-state NMR (ssNMR) spectroscopy has thus far limited the
      routine application of multidimensional experiments to determine the structure of
      membrane proteins in lipid bilayers. Here, we demonstrate the advantage of using
      a recently developed class of experiments, polarization optimized experiments,
      for both static and MAS spectroscopy to achieve higher sensitivity and
      substantial time-savings for 2D and 3D experiments. We used sarcolipin, a single
      pass membrane protein, reconstituted in oriented bicelles (for oriented ssNMR)
      and multilamellar vesicles (for MAS ssNMR) as a benchmark. The restraints derived
      by these experiments are then combined into a hybrid energy function to allow
      simultaneous determination of structure and topology. The resulting structural
      ensemble converged to a helical conformation with a backbone RMSD ~0.44 A, a tilt
      angle of 24 degrees  +/- 1 degrees , and an azimuthal angle of 55 degrees  +/- 6
      degrees . This work represents a crucial first step toward obtaining high
      resolution structures of large membrane proteins using combined multidimensional
      oriented solid-state NMR and magic angle spinning solid-state NMR.

PMID- 23963725
TI  - Multicultural media outreach: increasing cancer information coverage in minority
      communities.
AB  - Ethnic media can serve as an opportunity for cancer education and outreach to
      minority communities. The National Cancer Institute developed the Multicultural
      Media Outreach (MMO) program which utilizes an integrated approach of both
      traditional and social media to disseminate evidence-based cancer education
      information for minority communities. The MMO program is the contact point for
      multicultural media outlets seeking evidence-based cancer information, education
      materials, minority spokespersons, and news tailored to minority communities
      affected by cancer health disparities. MMO developed Lifelines(r), a cancer
      education series that addresses cancer prevention, treatment, survivorship,
      clinical trials, and other cancer-related topics for African American, Hispanic,
      Asian American, American Indian, and Alaska Native audiences. Lifelines(r)
      content is disseminated through traditional media (radio, print, and television)
      as well as social media (web, Twitter, YouTube, and RSS feed). This article
      describes the MMO program and lessons learned to date. 

PMID- 23963726
TI  - Quaking, an RNA-binding protein, is a critical regulator of vascular smooth
      muscle cell phenotype.
AB  - RATIONALE: RNA-binding proteins are critical post-transcriptional regulators of
      RNA and can influence pre-mRNA splicing, RNA localization, and stability. The RNA
      binding protein Quaking (QKI) is essential for embryonic blood vessel
      development. However, the role of QKI in the adult vasculature, and in particular
      in vascular smooth muscle cells (VSMCs), is currently unknown. OBJECTIVE: We
      sought to determine the role of QKI in regulating adult VSMC function and
      plasticity. METHODS AND RESULTS: We identified that QKI is highly expressed by
      neointimal VSMCs of human coronary restenotic lesions, but not in healthy
      vessels. In a mouse model of vascular injury, we observed reduced neointima
      hyperplasia in Quaking viable mice, which have decreased QKI expression.
      Concordantly, abrogation of QKI attenuated fibroproliferative properties of
      VSMCs, while potently inducing contractile apparatus protein expression,
      rendering noncontractile VSMCs with the capacity to contract. We identified that
      QKI localizes to the spliceosome, where it interacts with the myocardin pre-mRNA
      and regulates the splicing of alternative exon 2a. This post-transcriptional
      event impacts the Myocd_v3/Myocd_v1 mRNA balance and can be modulated by mutating
      the quaking response element in exon 2a of myocardin. Furthermore, we identified
      that arterial damage triggers myocardin alternative splicing and is tightly
      coupled with changes in the expression levels of distinct QKI isoforms.
      CONCLUSIONS: We propose that QKI is a central regulator of VSMC phenotypic
      plasticity and that intervention in QKI activity can ameliorate pathogenic,
      fibroproliferative responses to vascular injury.

PMID- 23963728
TI  - Mechanistic study of the uptake/permeation of cell-penetrating peptides across a
      caco-2 monolayer and their stimulatory effect on epithelial insulin transport.
AB  - Our recent studies have demonstrated the potential of cell-penetrating peptides
      (CPPs) to significantly stimulate the intestinal absorption of therapeutic
      peptides and proteins. This study examined the mechanisms underlying the
      intestinal epithelial uptake and permeation of CPPs and their contribution to the
      enhanced absorption of insulin. Fluorescein-tagged octaarginine (R8) and
      penetratin were used as the promising CPPs, and in vitro uptake and permeation
      assays were conducted using Caco-2 cell monolayer. The assay conducted under low
      temperature conditions revealed that energy-dependent pathways are not involved
      in d-form arginines (d-R8) uptake or its stimulatory effect on insulin uptake.
      The Km value (3.82 MUM), calculated from the dose dependence of d-R8 uptake,
      suggested that a part of the d-R8 uptake was saturated at the functional
      concentration (60 MUM d-R8). An analysis based on the binding parameters of
      insulin and d-R8 also showed an increase in the uptake clearance of the insulin/d
      R8 complex, even at a saturated concentration of d-R8, implying that this complex
      is taken up by Caco-2 cells via pathways that differ from those that take up
      unbound d-R8. Thus, this study suggests that CPPs such as oligoarginines
      stimulate the intestinal epithelial transport of peptide and protein drugs via
      energy-independent unsaturable internalization.

PMID- 23963727
TI  - Proinflammatory stimuli engage Brahma related gene 1 and Brahma in endothelial
      injury.
AB  - RATIONALE: Endothelial dysfunction inflicted by inflammation is found in a host
      of cardiovascular pathologies. One hallmark event in this process is the
      aggregation and adhesion of leukocyte to the vessel wall mediated by the
      upregulation of adhesion molecules (CAM) in endothelial cells at the
      transcriptional level. The epigenetic modulator(s) of CAM transactivation and its
      underlying pathophysiological relevance remain poorly defined. OBJECTIVE: Our
      goal was to determine the involvement of Brahma related gene 1 (Brg1) and Brahma
      (Brm) in CAM transactivation and its relevance in the pathogenesis of
      atherosclerosis. METHODS AND RESULTS: In the present study, we report that
      proinflammatory stimuli augmented the expression of Brg1 and Brm in vitro in
      cultured endothelial cells and in vivo in arteries isolated from rodents.
      Overexpression of Brg1 and Brm promoted while knockdown of Brg1 and Brm abrogated
      transactivation of adhesion molecules and leukocyte adhesion induced by
      inflammatory signals. Brg1 and Brm interacted with and were recruited to the CAM
      promoters by nuclear factor kappaB/p65. Conversely, depletion of Brg1 and Brm
      disrupted the kinetics of p65 binding on CAM promoters and crippled CAM
      activation. Silencing of Brg1 and Brm also altered key epigenetic changes
      associated with CAM transactivation. Of intrigue, 17beta-estradiol antagonized
      both the expression and activity of Brg1/Brm. Most importantly, endothelial
      targeted elimination of Brg1/Brm conferred atheroprotective effects to Apoe(-/-)
      mice on a Western diet. CONCLUSIONS: Our data suggest that Brg1 and Brm integrate
      various proinflammatory cues into CAM transactivation and endothelial malfunction
      and, as such, may serve as potential therapeutic targets in treating inflammation
      related cardiovascular diseases.

PMID- 23963729
TI  - Comparison of disease-specific quality of life tools in patients with chronic
      venous disease.
AB  - OBJECTIVES: This work was presented as a poster in the American Venous Forum 25th
      Annual Meeting; 28 February 2013; Phoenix, Arizona, USA. Quality of life (QoL) is
      an important outcome measure in the treatment for chronic venous disease. The
      Aberdeen Varicose Vein Questionnaire (AVVQ) and the ChronIc Venous Insufficiency
      quality of life Questionnaire (CIVIQ-14) are two validated disease-specific QoL
      questionnaires in current use. The aim of this study is to evaluate the
      relationship between the AVVQ and the CIVIQ-14 to enable better comparison
      between studies and to compare these disease-specific QoL tools with generic QoL
      and clinician-driven tools. METHODS: Adults attending our institution for
      management of their varicose veins completed the AVVQ, CIVIQ-14 and EuroQol-5D
      (EQ-5D). Clinical data, CEAP classification and the Venous Clinical Severity
      Score (VCSS) were collected. The relationship between the AVVQ and CIVIQ-14
      scores was analysed using Spearman's correlation. The AVVQ and CIVIQ-14 scores
      were also analysed with a generic QoL tool (EQ-5D) and a clinician-driven tool,
      the VCSS. RESULTS: One hundred patients, mean age 57.5 (44 males; 56 females),
      participated in the study. The median AVVQ score was 21.9 (range 0-74) and the
      median CIVIQ-14 score was 30 (range 0-89). A strong correlation was demonstrated
      between the AVVQ and CIVIQ-14 scores (r = 0.8; p < 0.0001). Strong correlation
      was maintained for patients with C1-3 disease (r = 0.7; p < 0.0001) and C4-6
      disease (r = 0.8; p < 0.0001). The VCSS correlated strongly with the AVVQ and
      CIVIQ-14 scores (r = 0.7; p < 0.0001 and r = 0.7; p < 0.0001, respectively). Both
      the AVVQ and CIVIQ-14 scores correlated well with the EQ-5D score (r = -0.5; p <
      0.0001 and r = -0.7; p < 0.0001, respectively). CONCLUSIONS: This study
      demonstrates that there is good correlation between two widely used varicose vein
      specific QoL tools (AVVQ and CIVIQ-14) across the whole spectrum of disease
      severity. Strong correlation exists between these disease-specific QoL tools and
      generic and clinician-driven tools. Our findings confirm valid comparisons
      between studies using either disease-specific QoL tool.

PMID- 23963730
TI  - Morphologically virus-like fullerenol nanoparticles act as the dual-functional
      nanoadjuvant for HIV-1 vaccine.
AB  - Fullerenol, which self-assembles into virus-sized nanoparticles, is designed as a
      dual-functional nanoadjuvant to generate comparable immune responses to the HIV
      DNA vaccine. It shows promising adjuvant activity via various immunization
      routes, decreasing the antigen dosage and immunization frequency while
      maintaining immunity levels and inducing TEM -biased immunity to combat the
      infection at early stage. The underlying mechanisms by which fullerenol-based
      formulation induces above-mentioned polyvalent immune responses are involved in
      activating multiple TLRs signaling pathways. 

PMID- 23963731
TI  - Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal
      function: the REPAIR-IDA trial.
AB  - BACKGROUND: Iron-deficiency anemia in non-dialysis-dependent chronic kidney
      disease (NDD-CKD) frequently requires parenteral iron replacement, but existing
      therapies often require multiple administrations. We evaluated the efficacy and
      cardiovascular safety of ferric carboxymaltose (FCM), a non-dextran parenteral
      iron permitting large single-dose infusions, versus iron sucrose in patients with
      iron-deficiency anemia and NDD-CKD. METHODS: A total of 2584 participants were
      randomized to two doses of FCM 750 mg in one week, or iron sucrose 200 mg
      administered in up to five infusions in 14 days. The primary efficacy endpoint
      was the mean change to highest hemoglobin from baseline to Day 56. The primary
      composite safety endpoint included all-cause mortality, nonfatal myocardial
      infarction, nonfatal stroke, unstable angina, congestive heart failure,
      arrhythmias and hyper- and hypotensive events. RESULTS: The mean hemoglobin
      increase was 1.13 g/dL in the FCM group and 0.92 g/dL in the iron sucrose group
      (95% CI, 0.13-0.28). Similar results were observed across all subgroups, except
      Stage 2 CKD. More subjects in the FCM group achieved a hemoglobin increase of >=
      1.0 g/dL between baseline and Day 56 (48.6 versus 41.0%; 95% CI, 3.6-11.6%).
      There was no significant difference between FCM and iron sucrose recipients with
      respect to the primary composite safety endpoint, including the major adverse
      cardiac events of death, myocardial infarction, or stroke. A significant
      difference in the number of protocol-defined, predominantly transient
      hypertensive episodes was observed in the FCM group. CONCLUSIONS: Two 750-mg
      infusions of FCM are a safe and effective alternative to multiple lower dose iron
      sucrose infusions in NDD-CKD patients with iron-deficiency anemia.

PMID- 23963732
TI  - Does change in hip circumference predict cardiovascular disease and overall
      mortality in Danish and Swedish women?
AB  - OBJECTIVE: Accumulating evidence consistently shows that small hip circumference
      (HC) is related to increased risk of cardiovascular disease (CVD), coronary heart
      disease, diabetes, and premature death in women. This study aims to clarify
      whether this inverse association can be found in both normal- and overweight
      individuals and if change in HC over time relates to morbidity and mortality
      risk. METHODS: HC and 6-year change in HC in relation to the risk for all-cause
      mortality and CVD morbidity and mortality was investigated in a pooled sample of
      2,867 women from the DANISH MONICA study and the Prospective Population Study of
      Women in Gothenburg with a total of 66,627 person-years of follow-up. RESULTS:
      Baseline HC was significantly and inversely associated with all-cause and CVD
      specific mortality after adjustment for BMI, waist circumference (WC), and other
      covariates. In stratified analyses, the inverse association was weaker in women
      with a BMI of more than 25 kg/m2. Six-year change in hip size was not associated
      with mortality or morbidity endpoints. CONCLUSIONS: Our results imply the
      existence of a basal risk associated with small hip size, which is, however,
      independent from changes in gluteofemoral body mass and therefore unlikely to be
      modifiable.

PMID- 23963733
TI  - Chromosomal speciation in mice: a cytogenetic analysis of recombination.
AB  - Within species, populations differing by chromosomal rearrangements ("chromosomal
      races") may become reproductively isolated in association with reduced hybrid
      fertility due to meiotic aberrations. Speciation is also possible if hybridizing
      chromosomal races accumulate genetic differences because of reduced meiotic
      recombination in the heterozygous configuration in hybrids. Here, we examine
      recombination in pure races and hybrids within a model system for chromosomal
      speciation: the hybridization of the Poschiavo (CHPO) and Upper Valtellina (IUVA)
      chromosomal races of house mouse in Upper Valtellina, Italy. These races differ
      by Robertsonian fusions/whole-arm reciprocal translocations, such that hybrids
      produce a pentavalent meiotic configuration. We determined the number and
      position of the recombination points (using an antibody against the MutL homolog
      1 [MLH1] protein) on synaptonemal complexes at pachytene in laboratory-reared
      CHPO, IUVA, and hybrid males, analyzing at least 112 spermatocytes per karyotypic
      group, up to a total of 534 spermatocytes. The mean +/- standard deviation
      numbers of MLH1 foci per spermatocyte were 22.2 +/- 3.2, 20.1 +/- 2.9, 20.7 +/-
      2.3, and 21.9 +/- 2.9 for CHPO, IUVA, CHPO * IUVA, and IUVA * CHPO, respectively.
      Altogether, 10,146 chromosome arms were examined, allowing multiple comparisons.
      Overall, recombination events were more frequently distal than proximal or
      interstitial. The average number of proximal MLH1 foci per chromosome arm
      decreased going from telocentric to metacentric bivalents to pentavalents (when
      present), which (together with other factors) influenced the average number of
      MLH1 foci per cell between CHPO, IUVA, and hybrid mice. The low frequency of
      proximal recombination in pentavalents of CHPO-IUVA hybrids may promote
      reproductive isolation between the CHPO and IUVA races, when coupled with reduced
      hybrid unfitness.

PMID- 23963734
TI  - Long-term efficacy of low-dose all-trans retinoic acid plus minimal chemotherapy
      induction followed by the addition of intravenous arsenic trioxide post-remission
      therapy in newly diagnosed acute promyelocytic leukaemia.
AB  - We evaluated the efficacy of low-dose all-trans retinoic acid (ATRA) plus minimal
      chemotherapy for induction in newly diagnosed acute promyelocytic leukaemia
      (APL). Furthermore, we compared its long-term outcome with or without the
      addition of intravenous arsenic trioxide (ATO) in post-remission therapy. From
      January 2004 to September 2011, a total of 109 patients with a median age of 41
      years (range 14-73) were enrolled in the study. Two arms were assigned according
      to post-remission protocols: ATO group cases were subsequently treated with
      intravenous ATO, standard chemotherapy, and ATRA. No-ATO group cases were
      subsequently treated with chemotherapy and ATRA only. Patients were monitored of
      minimal residual disease (MRD) by reverse-transcriptase polymerase chain
      reaction. The haematologic complete remission (CR) rate was 96.3%. The early
      death rate was 0.9%. At a median follow-up of 49 months (range 8-102 months), the
      Kaplan-Meier estimates of 5-year relapse-free survival were significantly better
      for patients in the ATO group than in the no-ATO group, 94.4% vs 54.8% (p =
      0.0001), and the 5-year overall survival rate was 95.7% vs 64.1%, in the two
      groups (p = 0.003). Our data show that low-dose ATRA plus minimal chemotherapy
      exhibits efficacy in induction therapy for untreated APL and suggest that the
      addition of ATO to post-remission therapy significantly improves the long-term
      outcome.

PMID- 23963735
TI  - Evaluation of the contralateral inguinal ring in clinically unilateral inguinal
      hernia: a systematic review and meta-analysis.
AB  - PURPOSE: The management of the contralateral inguinal canal in children with
      clinical unilateral inguinal hernia is controversial. Our objective was to
      systematically review the literature regarding management of the contralateral
      inguinal canal. METHODS: We searched MEDLINE, EMBASE, and Cochrane databases
      (1940-2011) using 'hernia' and 'inguinal' and either 'pediatric,' 'infant,' or
      'child,' to identify studies of pediatric (age <=21 years) patients with inguinal
      hernia. Among clinical unilateral hernia patients, we assessed the number of
      cases with contralateral patent processus (CPP) and incidence of subsequent
      clinical metachronous contralateral hernia (MCH). We evaluated three strategies
      for contralateral management: expectant management, laparoscopic evaluation or
      pre-operative ultrasound. Pooled estimates of MCH or CPP were generated with
      random effects by study when heterogeneity was found (I(2) > 50 %, or Cochrane's
      Q p >= 0.10). RESULTS: We identified 2,477 non-duplicated studies, 129 of which
      met our inclusion criteria and had sufficient information for quantitative
      analysis. The pooled incidence of MCH after open unilateral repair was 7.3 % (95
      % CI 6.5-8.1 %). Laparoscopic examination identified CPP in 30 % (95 % CI 26-34
      %). Lower age was associated with higher incidence of CPP (p < 0.01). The
      incidence of MCH after a negative laparoscopic evaluation was 0.9 % (95 % CI 0.5
      1.3 %). Significant heterogeneity was found in studies and pooled estimates
      should be interpreted with caution. CONCLUSIONS: The literature suggests that
      laparoscopically identified CPP is a poor indicator of future contralateral
      hernia. Almost a third of patients will have a CPP, while less than one in 10
      will develop MCH when managed expectantly. Performing contralateral hernia repair
      in patients with CPP results in overtreatment in roughly 2 out of 3 patients.

PMID- 23963736
TI  - Identification of DPPA4 and DPPA2 as a novel family of pluripotency-related
      oncogenes.
AB  - In order to identify novel pluripotency-related oncogenes, an expression screen
      for oncogenic foci-inducing genes within a retroviral human embryonic stem cell
      cDNA library was conducted. From this screen, we identified not only known
      oncogenes but also intriguingly the key pluripotency factor, DPPA4 (developmental
      pluripotency-associated four) that encodes a DNA binding SAP domain-containing
      protein. DPPA4 has not been previously identified as an oncogene but is highly
      expressed in embryonal carcinomas, pluripotent germ cell tumors, and other
      cancers. DPPA4 is also mutated in some cancers. In direct transformation assays,
      we validated that DPPA4 is an oncogene in both mouse 3T3 cells and immortalized
      human dermal fibroblasts. Overexpression of DPPA4 generates oncogenic foci
      (sarcoma cells) and causes anchorage-independent growth. The in vitro transformed
      cells also give rise to tumors in immunodeficient mice. Furthermore, functional
      analyses indicate that both the DNA-binding SAP domain and the histone-binding C
      terminal domain are critical for the oncogenic transformation activity of DPPA4.
      Downregulation of DPPA4 in E14 mouse embryonic stem cells and P19 mouse embryonic
      carcinoma cells causes decreased cell proliferation in each case. In addition,
      DPPA4 overexpression induces cell proliferation through genes related to
      regulation of G1/S transition. Interestingly, we observed similar findings for
      family member DPPA2. Thus, we have identified a new family of pluripotency
      related oncogenes consisting of DPPA2 and DPPA4. Our findings have important
      implications for stem cell biology and tumorigenesis.

PMID- 23963738
TI  - Maternal vitamin D deficiency causes smaller muscle fibers and altered transcript
      levels of genes involved in protein degradation, myogenesis, and cytoskeleton
      organization in the newborn rat.
AB  - SCOPE: Epidemiologic data reveal associations between low serum concentrations of
      25-hydroxyvitamin D (25(OH)D) and higher risk of falls and muscle weakness. Fetal
      stage is critical for the development of skeletal muscle, but little information
      is available on the impact of maternal vitamin D deficiency on muscles of
      offspring. METHODS AND RESULTS: To investigate the morphology and transcriptome
      of gastrocnemius muscle in newborns in response to maternal vitamin D deficiency,
      14 female rats were fed either a vitamin D3 deficient (0 IU/kg) or a vitamin D3
      adequate diet (1000 IU/kg) 8 weeks prior to conception, during pregnancy, and
      lactation. Analysis of cholecalciferol, 25(OH)D3 and 1,25-dihydroxyvitamin D3
      show that dams fed the vitamin D deficient diet and their newborns suffered from
      a relevant vitamin D deficiency. Muscle cells of vitamin D deficient newborns
      were smaller than those of vitamin D adequate newborns (p < 0.05). Muscle
      transcriptome of the newborns revealed 426 probe sets as differentially expressed
      (259 upregulated, 167 downregulated) in response to vitamin D deficiency (fold
      change >=1.5, p < 0.05). The effected genes are involved in protein catabolism,
      cell differentiation and proliferation, muscle cell development, and cytoskeleton
      organization. CONCLUSION: Maternal vitamin D deficiency has a major impact on
      morphology and gene expression profile of skeletal muscle in newborns.

PMID- 23963737
TI  - Mutagenic dissection of the sequence determinants of protein folding,
      recognition, and machine function.
AB  - Understanding the relationship between the amino-acid sequence of a protein and
      its ability to fold and to function is one of the major challenges of protein
      science. Here, cases are reviewed in which mutagenesis, biochemistry, structure
      determination, protein engineering, and single-molecule biophysics have
      illuminated the sequence determinants of folding, binding specificity, and
      biological function for DNA-binding proteins and ATP-fueled machines that
      forcibly unfold native proteins as a prelude to degradation. In addition to
      structure-function relationships, these studies provide information about folding
      intermediates, mutations that accelerate folding, slow unfolding, and stabilize
      proteins against denaturation, show how new binding specificities and folds can
      evolve, and reveal strategies that proteolytic machines use to recognize, unfold,
      and degrade thousands of distinct substrates. 

PMID- 23963739
TI  - Midwife-led continuity models versus other models of care for childbearing women.
AB  - BACKGROUND: Midwives are primary providers of care for childbearing women around
      the world. However, there is a lack of synthesised information to establish
      whether there are differences in morbidity and mortality, effectiveness and
      psychosocial outcomes between midwife-led continuity models and other models of
      care. OBJECTIVES: To compare midwife-led continuity models of care with other
      models of care for childbearing women and their infants. SEARCH METHODS: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28
      January 2013) and reference lists of retrieved studies. SELECTION CRITERIA: All
      published and unpublished trials in which pregnant women are randomly allocated
      to midwife-led continuity models of care or other models of care during pregnancy
      and birth. DATA COLLECTION AND ANALYSIS: All review authors evaluated
      methodological quality. Two review authors checked data extraction. MAIN RESULTS:
      We included 13 trials involving 16,242 women. Women who had midwife-led
      continuity models of care were less likely to experience regional analgesia
      (average risk ratio (RR) 0.83, 95% confidence interval (CI) 0.76 to 0.90),
      episiotomy (average RR 0.84, 95% CI 0.76 to 0.92), and instrumental birth
      (average RR 0.88, 95% CI 0.81 to 0.96), and were more likely to experience no
      intrapartum analgesia/anaesthesia (average RR 1.16, 95% CI 1.04 to 1.31),
      spontaneous vaginal birth (average RR 1.05, 95% CI 1.03 to 1.08), attendance at
      birth by a known midwife (average RR 7.83, 95% CI 4.15 to 14.80), and a longer
      mean length of labour (hours) (mean difference (hours) 0.50, 95% CI 0.27 to
      0.74). There were no differences between groups for caesarean births (average RR
      0.93, 95% CI 0.84 to 1.02).Women who were randomised to receive midwife-led
      continuity models of care were less likely to experience preterm birth (average
      RR 0.77, 95% CI 0.62 to 0.94) and fetal loss before 24 weeks' gestation (average
      RR 0.81, 95% CI 0.66 to 0.99), although there were no differences in fetal
      loss/neonatal death of at least 24 weeks (average RR 1.00, 95% CI 0.67 to 1.51)
      or in overall fetal/neonatal death (average RR 0.84, 95% CI 0.71 to 1.00).Due to
      a lack of consistency in measuring women's satisfaction and assessing the cost of
      various maternity models, these outcomes were reported narratively. The majority
      of included studies reported a higher rate of maternal satisfaction in the
      midwifery-led continuity care model. Similarly there was a trend towards a cost
      saving effect for midwife-led continuity care compared to other care models.
      AUTHORS' CONCLUSIONS: Most women should be offered midwife-led continuity models
      of care and women should be encouraged to ask for this option although caution
      should be exercised in applying this advice to women with substantial medical or
      obstetric complications.

PMID- 23963740
TI  - The transmitting tissue of Nicotiana tabacum is not essential to pollen tube
      growth, and its ablation can reverse prezygotic interspecific barriers.
AB  - The Nicotiana tabacum transmitting tissue is a highly specialized file of
      metabolically active cells that is the pathway for pollen tubes from the stigma
      to the ovules where fertilization occurs. It is thought to be essential to pollen
      tube growth because of the nutrients and guidance it provides to the pollen
      tubes. It also regulates gametophytic self-incompatibility in the style. To test
      the function of the transmitting tissue in pollen tube growth and to determine
      its role in regulating prezygotic interspecific incompatibility, genetic ablation
      was used to eliminate the mature transmitting tissue, producing a hollow style.
      Despite the absence of the mature transmitting tissue and greatly reduced
      transmitting-tissue-specific gene expression, self-pollen tubes had growth to the
      end of the style. Pollen tubes grew at a slower rate in the transmitting-tissue
      ablated line during the first 24 h post-pollination. However, pollen tubes grew
      to a similar length 40 h post-pollination with and without a transmitting tissue.
      Ablation of the N. tabacum transmitting tissue significantly altered
      interspecific pollen tube growth. These results implicate the N. tabacum
      transmitting tissue in facilitating or inhibiting interspecific pollen tube
      growth in a species-dependent manner and in controlling prezygotic reproductive
      barriers. 

PMID- 23963741
TI  - EFSA's scientific activities and achievements on the risk assessment of
      genetically modified organisms (GMOs) during its first decade of existence:
      looking back and ahead.
AB  - Genetically modified organisms (GMOs) and derived food and feed products are
      subject to a risk analysis and regulatory approval before they can enter the
      market in the European Union (EU). In this risk analysis process, the role of the
      European Food Safety Authority (EFSA), which was created in 2002 in response to
      multiple food crises, is to independently assess and provide scientific advice to
      risk managers on any possible risks that the use of GMOs may pose to human and
      animal health and the environment. EFSA's scientific advice is elaborated by its
      GMO Panel with the scientific support of several working groups and EFSA's GMO
      Unit. This review presents EFSA's scientific activities and highlights its
      achievements on the risk assessment of GMOs for the first 10 years of its
      existence. Since 2002, EFSA has issued 69 scientific opinions on genetically
      modified (GM) plant market registration applications, of which 62 for import and
      processing for food and feed uses, six for cultivation and one for the use of
      pollen (as or in food), and 19 scientific opinions on applications for marketing
      products made with GM microorganisms. Several guidelines for the risk assessment
      of GM plants, GM microorganisms and GM animals, as well as on specific issues
      such as post-market environmental monitoring (PMEM) were elaborated. EFSA also
      provided scientific advice upon request of the European Commission on safeguard
      clause and emergency measures invoked by EU Member States, annual PMEM reports,
      the potential risks of new biotechnology-based plant breeding techniques,
      evaluations of previously assessed GMOs in the light of new scientific
      publications, and the use of antibiotic resistance marker genes in GM plants.
      Future challenges relevant to the risk assessment of GMOs are discussed. EFSA's
      risk assessments of GMO applications ensure that data are analysed and presented
      in a way that facilitates scientifically sound decisions that protect human and
      animal health and the environment. 

PMID- 23963742
TI  - Assessment of chromium content of feedstuffs, their estimated requirement, and
      effects of dietary chromium supplementation on nutrient utilization, growth
      performance, and mineral balance in summer-exposed buffalo calves (Bubalus
      bubalis).
AB  - This study was conducted to determine the chromium content of different
      feedstuffs, their estimated requirement, and effect of dietary Cr supplementation
      on nutrient intake, nutrient utilization, growth performance, and mineral balance
      in buffalo calves during summer season. Levels of Cr was higher in cultivated
      fodder, moderate in cakes and cereal grains, while straw, grasses, and non
      conventional feeds were poor in Cr content. To test the effect of Cr
      supplementation in buffalo calves, 0, 0.5, 1.0, and 1.5 ppm of inorganic Cr were
      fed to 24 buffalo calves. Buffalo calves were randomly assigned to four
      treatments (n = 6) and raised for 120 days. A metabolic trial for a period of 7
      days was conducted after 3 months of dietary treatments. Blood samples were
      collected at fortnight interval for plasma mineral estimation. The results
      suggested that dietary Cr supplementation in summer did not have any affects (P >
      0.05) on feed consumption, growth performance, nitrogen balance, and
      physiological variables. However, dietary Cr supplementation had significant
      effect (P < 0.05) on balance and plasma Cr (ppb) levels without affecting (P >
      0.05) balance and plasma levels of other trace minerals. The estimated Cr
      requirement of buffalo calves during summer season was calculated to be 0.044
      mg/kg body mass and 10.37 ppm per day. In conclusion, dietary Cr supplementation
      has regardless effect on feed consumption, mass gain, and nutrient utilization in
      buffalo calves reared under heat stress conditions. However, supplementation of
      Cr had positive effect on its balance and plasma concentration without
      interacting with other trace minerals.

PMID- 23963743
TI  - Evidence for the role of AMPK in regulating PGC-1 alpha expression and
      mitochondrial proteins in mouse epididymal adipose tissue.
AB  - OBJECTIVE: PGC-1alpha is a transcriptional co-activator and master regulator of
      mitochondrial biogenesis. While extensively studied in skeletal and cardiac
      muscle, recent findings suggest that white adipose tissue PGC-1alpha plays an
      important role in regulating glucose homeostasis. The purpose of the present
      investigation was to evaluate the role of AMPK in regulating PGC-1alpha and
      mitochondrial enzymes in mouse epididymal and inguinal subcutaneous adipose
      tissue. METHODS: Mitochondrial protein content and norepinephrine and CL 316,243
      induced PGC-1alpha mRNA expression were studied in mouse epididymal and inguinal
      adipose tissue from wild-type and AMPK beta1(-/-) mice. RESULTS: The protein
      content and phosphorylation of AMPKalpha was reduced in epididymal adipose tissue
      from AMPK beta1(-/-) compared to WT mice, concomitant with decreases in PGC
      1alpha and mitochondrial marker proteins. Norepinephrine and CL 316,243-mediated
      induction of PGC-1alpha were decreased in cultured epididymal adipose tissue from
      AMPK beta1(-/-) relative to WT mice. In inguinal adipose tissue from AMPK beta1(
      /-) mice, mitochondrial marker protein content and norepinephrine and CL 316,243
      mediated increases in PGC-1alpha were normal despite reductions in the content
      and phosphorylation of AMPKalpha. CONCLUSIONS: Norepinephrine- and CL 316,243
      mediated induction of PGC-1alpha and mitochondrial protein expression is
      regulated by AMPK in epididymal, but not inguinal adipose tissue.

PMID- 23963744
TI  - On the links between elastic constants and effective elastic behavior of
      pharmaceutical compacts: importance of poisson's ratio and use of bulk modulus.
AB  - The elastic properties of pharmaceutical powders and compacts are of great
      interest to understand the complex phenomena that occur during and after the
      tableting process. The elastic recovery after compression is known to be linked
      with adverse phenomena such as capping or delamination of tablets. Classically,
      the elastic behavior is modeled using linear elasticity and is characterized
      using only Young's modulus (E), often by using a value extrapolated at zero
      porosity. In this work, four pharmaceutical products were studied. The elastic
      behavior of compacts obtained using a large range of applied pressure was
      characterized. First, it was found more suitable to use apparent elastic moduli
      than extrapolations at zero porosity. Then, the results indicate that there was
      not always a good correlation between the values of Young's modulus and the
      actual elastic recovery of the compacts. Poisson's ratio (v), which differs from
      one product to another and is porosity-dependent, must be taken into account.
      Finally, the bulk modulus (K), which combines E and v, was shown to be well
      correlated with the elastic recovery of the compacts and can be considered as a
      relevant parameter to characterize the elastic behavior of pharmaceutical
      compacts.

PMID- 23963745
TI  - Neurobehavioral profiles in individuals with hyperimmunoglobulin E Syndrome
      (HIES) and brain white matter hyperintensities.
AB  - PURPOSE: Individuals with hyperimmunoglobulin E Syndrome (HIES) have central
      nervous system abnormalities, including focal white matter hyperintensities
      (WMH), or unidentified bright objects. This cross-sectional study aimed to
      describe the cognitive and emotional functioning and quality of life of people
      with HIES. We also sought to explore the relationship between cognitive
      functioning and WMHs in this population. METHODS: Twenty-nine individuals (13
      males) with autosomal-dominant HIES (mean age = 35.1 years, range 16-55) were
      administered a comprehensive psychological assessment as part of a natural
      history protocol. The assessment included measures of global cognitive
      functioning (Wechsler Adult Intelligence Scale-III), memory (California Verbal
      Learning Test-II, Wechsler Memory Scale-III), executive skills (Delis Kaplan
      Executive Function System), and attention (Test of Everyday Attention). Emotional
      symptoms and quality of life also were assessed. RESULTS: All mean cognitive
      scores were within normal limits. Mean scores on memory and executive functioning
      measures were significantly lower than Full Scale IQ scores (ps < .05).
      Substantial percentages of patients self-reported executive skills to be in the
      clinical range. Patients with fewer (1-20) versus more (21+) WMHs scored
      significantly better on measures of global cognitive skills, visual-perceptual
      skills, and working memory. Mean scores on emotional symptom and quality of life
      measures were in the average range and unrelated to WMHs. CONCLUSIONS: Global
      cognitive functioning was average to high average in our sample of individuals
      with HIES. However, focal brain lesions were associated with lower scores in
      specific domains. Emotional functioning and quality of life are within normal
      limits in this sample.

PMID- 23963746
TI  - Yield of molecular and clinical testing for arrhythmia syndromes: report of 15
      years' experience.
AB  - BACKGROUND: Sudden cardiac death is often caused by inherited arrhythmia
      syndromes, particularly if it occurs at a young age. In 1996, we started a
      cardiogenetics clinic aimed at diagnosing such syndromes and providing timely
      (often presymptomatic) treatment to families in which such syndromes or sudden
      cardiac death existed. We studied the yield of DNA testing for these syndromes
      using a candidate-gene approach over our 15 years of experience. METHODS AND
      RESULTS: We analyzed the yield of DNA testing. In subanalyses, we studied
      differences in the yield of DNA testing over time, between probands with isolated
      or familial cases and between probands with or without clear disease-specific
      clinical characteristics. In cases of sudden unexplained death (antemortem or
      postmortem analysis of the deceased not performed or providing no diagnosis), we
      analyzed the yield of cardiological investigations. Among 7021 individuals who
      were counseled, 6944 from 2298 different families (aged 41 +/- 19 years; 49%
      male) were analyzed. In 702 families (31%), a possible disease-causing mutation
      was detected. Most mutations were found in families with long-QT syndrome (47%)
      or hypertrophic cardiomyopathy (46%). Cascade screening revealed 1539 mutation
      positive subjects. The mutation detection rate decreased over time, in part
      because probands with a less severe phenotype were studied, and was significantly
      higher in familial than in isolated cases. We counseled 372 families after sudden
      unexplained death; in 29% of them (n=108), an inherited arrhythmia syndrome was
      diagnosed. CONCLUSIONS: The proportion of disease-causing mutations found
      decreased over time, in part because probands with a less severe phenotype were
      studied. Systematic screening of families identified many (often presymptomatic)
      mutation-positive subjects.

PMID- 23963747
TI  - Aligned nano-porous microwave exfoliated graphite oxide ionic actuators with high
      strain and elastic energy density.
AB  - A high-density aligned nanoporous activated microwave exfoliated graphite oxide
      (aMEGO) ionic actuator is studied. Before applying an external electric field,
      the cations and anions are randomly distributed in the composite. After applying
      the electric field, ions ingress in between the aligned aMEGO sheets through the
      nanopores to compensate the charges on the electrodes, resulting in the
      separation of neighboring sheets and unidirectional electro actuation. 

PMID- 23963748
TI  - Transmission of acoustic emission in bones, implants and dental materials.
AB  - There is considerable interest in using acoustic emission (AE) and ultrasound to
      assess the quality of implant-bone interfaces and to monitor for micro-damage
      leading to loosening. However, remarkably little work has been done on the
      transmission of ultrasonic waves though the physical and biological structures
      involved. The aim of this in vitro study is to assess any differences in
      transmission between various dental materials and bovine rib bones with various
      degrees of hydration. Two types of tests have been carried out using pencil lead
      breaks as a standard AE source. The first set of tests was configured to assess
      the surface propagation of AE on various synthetic materials compared with fresh
      bovine rib bone. The second is a set of transmission tests on fresh, dried and
      hydrated bones each fitted with dental implants with various degrees of fixity,
      which includes components due to bone and interface transmission. The results
      indicate that transmission through glass ionomer cement is closest to the bone.
      This would suggest that complete osseointegration could potentially be simulated
      using such cement. The transmission of AE energy through bone was found to be
      dependent on its degree of hydration. It was also found that perfusing samples of
      fresh bone with water led to an increase in transmitted energy, but this appeared
      to affect transmission across the interface more than transmission through the
      bone. These findings have implications not only for implant interface inspection
      but also for passive AE monitoring of implants. 

PMID- 23963749
TI  - The L450F [Corrected] mutation in KCND3 brings spinocerebellar ataxia and Brugada
      syndrome closer together.

PMID- 23963750
TI  - Menstrual cycle abnormalities in healthy women with low physical activity. The
      North-Trondelag population-based health study.
AB  - BACKGROUND: Menstrual dysfunctions are often found in athletic women. This study
      evaluated the association between leisure time physical activity (LTPA) and
      menstrual function in healthy nonathletic women. METHODS: During 1984-1986, a
      population-based health survey (HUNT 1) was conducted in Nord-Trondelag, Norway,
      with follow-up (HUNT 2) in 1995-1997. Women < 45 years old in HUNT 2 were
      included in the current study. LTPA was assessed by questionnaire in HUNT 1 and
      HUNT 2, and menstrual function by questionnaire in HUNT 2. RESULTS: Adjusted odds
      ratios (OR's) for long cycles were increased in women who reported < 1 hour of
      light LTPA (OR = 1.4, 95% CI = 1.0-2.0) and 1-2 hours (OR = 1.3, 95% CI = 1.0
      1.8) per week compared with women with >= 3 hours/week. Adjusted OR for irregular
      cycles was decreased in women constantly in the lowest tertile of LTPA index in
      HUNT 1 and HUNT 2 (OR = 0.4, 95% CI = 0.2-0.9). Adjusted OR for prolonged
      bleeding was 2.6 (95% CI = 1.3-5.4) for women with < 1 hour/week of light LTPA
      and 2.3 (95% CI = 1.3-4.3) for women with 1-2 hours, compared with >= 3
      hours/week. CONCLUSIONS: Very low physical activity may increase the risk of
      menstrual cycle disruptions. Moderate PA should be encouraged for optimum
      reproductive health.

PMID- 23963751
TI  - Exposure of breastfed infants to quercetin after consumption of a single meal
      rich in quercetin by their mothers.
AB  - SCOPE: The exposure to quercetin (Q) has not been studied in breastfed infants
      whose mothers were consuming a Q-rich diet. The objective of the study was to
      determine whether plant-origin antioxidant-Q passes from the mother's diet to her
      milk and to calculate the pharmacokinetic parameters of this phenomenon. METHODS
      AND RESULTS: Eleven breastfeeding women were included in this controlled case
      study. Volunteers followed a Q-restricted diet for 5 consecutive days with the
      exception of the 3rd day when they received a single meal providing 1 mg of Q per
      kg of body weight. Urine analysis showed the presence of Q already in the first
      collected samples after the test (1.5-4 h), which indicated its rapid absorption
      from the meal. The Cmax = 68 +/- 8.44 nmol/L concentration of Q in the milk was
      calculated for Tmax = 11.89 +/- 3.37 h. It was significantly different (p =
      0.007) from 40 nmol/L and (p = 0.016) from 42 nmol/L of Q concentration before
      and 48 h after the test, respectively. CONCLUSIONS: Q was shown to be a component
      of human milk at the nmol/L level. Infants breastfed by mothers consuming a diet
      rich in Q are exposed to a dose of approximately 0.01 mg of Q daily.

PMID- 23963752
TI  - Gene therapy to treat cardiovascular disease.

PMID- 23963753
TI  - Hydrogen peroxide-mediated SERCA cysteine 674 oxidation contributes to impaired
      cardiac myocyte relaxation in senescent mouse heart.
AB  - BACKGROUND: A hallmark of aging of the cardiac myocyte is impaired sarcoplasmic
      reticulum (SR) calcium uptake and relaxation due to decreased SR calcium ATPase
      (SERCA) activity. We tested the hypothesis that H2O2-mediated oxidation of SERCA
      contributes to impaired myocyte relaxation in aging. METHODS AND RESULTS: Young
      (5-month-old) and senescent (21-month-old) FVB wild-type (WT) or transgenic mice
      with myocyte-specific overexpression of catalase were studied. In senescent mice,
      myocyte-specific overexpression of catalase (1) prevented oxidative modification
      of SERCA as evidenced by sulfonation at Cys674, (2) preserved SERCA activity, (3)
      corrected impaired calcium handling and relaxation in isolated cardiac myocytes,
      and (4) prevented impaired left ventricular relaxation and diastolic dysfunction.
      Nitroxyl, which activates SERCA via S-glutathiolation at Cys674, failed to
      activate SERCA in freshly isolated ventricular myocytes from senescent mice.
      Finally, in adult rat ventricular myocytes in primary culture, adenoviral
      overexpression of SERCA in which Cys674 is mutated to serine partially preserved
      SERCA activity during exposure to H2O2. CONCLUSION: Oxidative modification of
      SERCA at Cys674 contributes to decreased SERCA activity and impaired myocyte
      relaxation in the senescent heart. Strategies to decrease oxidant levels and/or
      protect target proteins such as SERCA may be of value to preserve diastolic
      function in the aging heart.

PMID- 23963754
TI  - Effect of premeasurement rest time on systolic ankle pressure.
AB  - BACKGROUND: Systolic ankle pressures are routinely measured as part of an ankle
      brachial index to screen for lower extremity peripheral arterial disease. Despite
      widespread use of this measurement, the effect of premeasurement duration of rest
      on the magnitude, or reliability of the ankle systolic pressure measurement is
      unknown. This study assessed the effect of premeasurement rest duration on
      systolic ankle pressures. METHODS AND RESULTS: One hundred and forty participants
      meeting guidelines for peripheral arterial disease screening volunteered for this
      study. Following 5 minutes of rest in the supine horizontal position, ankle
      systolic pressures of the lower extremity were taken. Measurements were repeated
      at 10 and 15 minutes. Testing was repeated 7 to 10 days later. A significant drop
      in ankle pressure of 5.02 mm Hg occurred between 5 and 10 minutes (P=0.004). No
      significant change occurred between 10 and 15 minutes (mean change 0.15 mm Hg,
      P=0.99). Presence of diabetes was associated with a smaller drop between 5 and 15
      minutes (mean change 1.85 mm Hg) and predicted 13.4% of the variance in change in
      ankle pressure (beta=-3.61, P=0.0001). Test-retest reliability after 5 minutes
      was excellent (intraclass correlation coefficient: 0.84, 95% CI: 0.76 to 0.91)
      however increased for measurements taken at 10 and 15 minutes (intraclass
      correlation coefficient: 0.89 95% CI: 0.83 to 0.94 and 0.89 95% CI: 0.82 to
      0.93). CONCLUSIONS: Results suggest ankle systolic pressures stabilise after 10
      minutes of rest. Longer periods of premeasurement rest did not improve
      reliability significantly. Though diabetes affects ankle pressure changes after
      rest, further investigation is required to identify the cause.

PMID- 23963755
TI  - Increased atherosclerotic lesions in LDL receptor deficient mice with
      hematopoietic nuclear receptor Rev-erbalpha knock- down.
AB  - BACKGROUND: Nuclear receptor Rev-erbalpha plays important roles in circadian
      clock timing, lipid metabolism, adipogenesis, and vascular inflammation. However,
      the role of Rev-erbalpha in atherosclerotic lesion development has not been
      assessed in vivo. METHODS AND RESULTS: The nuclear receptor Rev-erbalpha was
      knocked down in mouse haematopoietic cells by means of shRNA-lentiviral
      transduction, followed by bone marrow transplantation into LDL receptor knockout
      mice. The Rev-erbalpha protein in peripheral macrophage was reduced by 70% as
      compared to control mice injected with nontargeting shRNA lentivirus-transduced
      bone marrow. A significant increase in atherosclerotic lesions was observed
      around the aorta valves as well as upon en face aorta analysis of Rev-erbalpha
      knock-down bone marrow recipients (P<0.01) as compared to the control mice, while
      plasma cholesterol, phospholipid, and triacylglycerol levels were not affected.
      Overexpression of Rev-erbalpha in bone marrow mononuclear cells decreased
      inflammatory M1 while increasing M2 macrophage markers, while Rev-erbalpha knock
      down increased the macrophage inflammatory phenotype in vitro and in vivo.
      Furthermore, treatment of differentiating macrophages with the Rev-erbalpha
      ligand heme promoted expression of antiinflammatory M2 markers. CONCLUSIONS:
      These observations identify hematopoietic cell Rev-erbalpha as a new modulator of
      atherogenesis in mice.

PMID- 23963756
TI  - Trials to improve blood pressure through adherence to antihypertensives in
      stroke/TIA: systematic review and meta-analysis.
AB  - BACKGROUND: The purpose of this study was to determine whether interventions
      including components to improve adherence to antihypertensive medications in
      patients after stroke/transient ischemic attack (TIA) improve adherence and blood
      pressure control. METHODS AND RESULTS: We searched MEDLINE, EMBASE, CINAHL, BNI,
      PsycINFO, and article reference lists to October 2012. Search terms included
      stroke/TIA, adherence/prevention, hypertension, and randomized controlled trial
      (RCT). Inclusion criteria were participants with stroke/TIA; interventions
      including a component to improve adherence to antihypertensive medications; and
      outcomes including blood pressure, antihypertensive adherence, or both. Two
      reviewers independently assessed studies to determine eligibility, validity, and
      quality. Seven RCTs were eligible (n=1591). Methodological quality varied. All
      trials tested multifactorial interventions. None targeted medication adherence
      alone. Six trials measured blood pressure and 3 adherence. Meta-analysis of 6
      trials showed that multifactorial programs were associated with improved blood
      pressure control. The difference between intervention versus control in mean
      improvement in systolic blood pressure was -5.3 mm Hg (95% CI, -10.2 to -0.4 mm
      Hg, P=0.035; I(2)=67% [21% to 86%]) and in diastolic blood pressure was -2.5 mm
      Hg (-5.0 to -0.1 mm Hg, P=0.046; I(2)=47% [0% to 79%]). There was no effect on
      medication adherence where measured. CONCLUSIONS: Multifactorial interventions
      including a component to improve medication adherence can lower blood pressure
      after stroke/TIA. However, it is not possible to say whether or not this is
      achieved through better medication adherence. Trials are needed of well
      characterized interventions to improve medication adherence and clinical outcomes
      with measurement along the hypothesized causal pathway.

PMID- 23963757
TI  - Leukoaraiosis and increased cerebral susceptibility to ischemia: lack of
      confounding by carotid disease.
AB  - BACKGROUND: Leukoaraiosis is associated with an increased risk of stroke, but the
      underlying mechanism remains uncertain, as do the associations with other risk
      factors, such as carotid disease. We aimed to determine the role of carotid
      disease and of other clinical variables in the development of leukoaraiosis and
      to define their contributions to the associated increased risk of stroke. METHODS
      AND RESULTS: We prospectively studied a large cohort of consecutive patients with
      transient ischemic attack (TIA) and minor stroke who attended a TIA clinic
      between 2002 and 2009. Detailed clinical data were obtained, and patients
      underwent magnetic resonance brain and vascular imaging. We assessed the severity
      of leukoaraiosis with use of the ARWMC (Age Related White Matter Changes) score:
      671 patients (374 [56%] men; mean [SD] age 71 [11] years) were studied, of whom
      415 (62%) had leukoaraiosis. In a multivariate analysis, leukoaraiosis was
      associated with increasing age (P<0.0001) and hypertension (P=0.01), as well as
      the presence of acute (P<0.0001) and chronic (P=0.014) infarction on magnetic
      resonance imaging. In the univariate analysis, a current and past diagnosis of
      stroke versus TIA also showed a strong association. Carotid disease was not
      associated with leukoaraiosis, even in the presence of a flow-limiting (>70%)
      stenosis or occlusion, and the risk factor profiles for leukoaraiosis and carotid
      disease differed. CONCLUSIONS: The association with more severe ischemic events
      (stroke versus TIA) and infarction on imaging is consistent with leukoaraiosis
      being a marker of increased cerebral susceptibility to ischemia. In contrast, the
      presence, severity of, and risk factors for atheromatous disease showed no
      association with leukoaraiosis, suggesting that these are two unrelated disease
      processes.

PMID- 23963758
TI  - Myocardial tissue remodeling in adolescent obesity.
AB  - BACKGROUND: Childhood obesity is a significant risk factor for cardiovascular
      disease in adulthood. Although ventricular remodeling has been reported in obese
      youth, early tissue-level markers within the myocardium that precede organ-level
      alterations have not been described. METHODS AND RESULTS: We studied 21 obese
      adolescents (mean age, 17.7+/-2.6 years; mean body mass index [BMI], 41.9+/-9.5
      kg/m(2), including 11 patients with type 2 diabetes [T2D]) and 12 healthy
      volunteers (age, 15.1+/-4.5 years; BMI, 20.1+/-3.5 kg/m(2)) using biomarkers of
      cardiometabolic risk and cardiac magnetic resonance imaging (CMR) to phenotype
      cardiac structure, function, and interstitial matrix remodeling by standard
      techniques. Although left ventricular ejection fraction and left atrial volumes
      were similar in healthy volunteers and obese patients (and within normal body
      size-adjusted limits), interstitial matrix expansion by CMR extracellular volume
      fraction (ECV) was significantly different between healthy volunteers (median,
      0.264; interquartile range [IQR], 0.253 to 0.271), obese adolescents without T2D
      (median, 0.328; IQR, 0.278 to 0.345), and obese adolescents with T2D (median,
      0.376; IQR, 0.336 to 0.407; P=0.0001). ECV was associated with BMI for the entire
      population (r=0.58, P<0.001) and with high-sensitivity C-reactive protein
      (r=0.47, P<0.05), serum triglycerides (r=0.51, P<0.05), and hemoglobin A1c
      (r=0.76, P<0.0001) in the obese stratum. CONCLUSIONS: Obese adolescents
      (particularly those with T2D) have subclinical alterations in myocardial tissue
      architecture associated with inflammation and insulin resistance. These
      alterations precede significant left ventricular hypertrophy or decreased cardiac
      function.

PMID- 23963760
TI  - No clinical evidence for performing trough plasma and intracellular imatinib
      concentrations monitoring in patients with chronic myelogenous leukaemia.
AB  - This multicentre study focused on monitoring imatinib mesylate (IMA) trough
      plasma (Ctrough ) and intracellular (IMA Cintrac ) concentrations in 228 chronic
      myelogenous leukaemia patients. The median of measured IMA Ctrough in our patient
      group was 905.8 ng ml (range: 27.7-4628.1 ng/ml). We found a correlation between
      IMA Ctrough and alpha 1-acid glycoprotein plasma concentrations (rS = 0.42; p <
      0.001). All other analysed parameters revealed only weak (gender, dose of IMA per
      kg) or not significant (age, albumin, creatinine plasma concentration or body
      mass index) impact on measured IMA Ctrough. The IMA Ctrough decreased during the
      first 6 months and significantly increased later during treatment. The IMA
      Ctrough at the first month of therapy did not differ between patients with and
      without an optimal response at the 12th (p = 0.724) and 18th month (p = 0.135) of
      therapy. There were no significant differences in medians of IMA Ctrough between
      both groups measured during the first year of treatment. The IMA Cintrac during
      the first month were not different between patients with and without an optimal
      response at the 6th (p = 0.273) and the 12th month (p = 0.193) of therapy. Our
      data obtained from real life clinical practice did not find a benefit of routine
      and regular IMA Ctrough nor IMA Cintrac therapeutic drug monitoring in chronic
      myelogenous leukaemia patients or for subsequent adjustments of the IMA dose
      based on these results. Moreover, actual alpha 1-acid glycoprotein plasma
      concentration should be used for proper interpretation of IMA Ctrough results.

PMID- 23963759
TI  - Long-term miR-669a therapy alleviates chronic dilated cardiomyopathy in
      dystrophic mice.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is a leading cause of chronic morbidity
      and mortality in muscular dystrophy (MD) patients. Current pharmacological
      treatments are not yet able to counteract chronic myocardial wastage, thus novel
      therapies are being intensely explored. MicroRNAs have been implicated as fine
      regulators of cardiomyopathic progression. Previously, miR-669a downregulation
      has been linked to the severe DCM progression displayed by Sgcb-null dystrophic
      mice. However, the impact of long-term overexpression of miR-669a on muscle
      structure and functionality of the dystrophic heart is yet unknown. METHODS AND
      RESULTS: Here, we demonstrate that intraventricular delivery of adeno-associated
      viral (AAV) vectors induces long-term (18 months) miR-669a overexpression and
      improves survival of Sgcb-null mice. Treated hearts display significant decrease
      in hypertrophic remodeling, fibrosis, and cardiomyocyte apoptosis. Moreover, miR
      669a treatment increases sarcomere organization, reduces ventricular atrial
      natriuretic peptide (ANP) levels, and ameliorates gene/miRNA profile of DCM
      markers. Furthermore, long-term miR-669a overexpression significantly reduces
      adverse remodeling and enhances systolic fractional shortening of the left
      ventricle in treated dystrophic mice, without significant detrimental
      consequences on skeletal muscle wastage. CONCLUSIONS: Our findings provide the
      first evidence of long-term beneficial impact of AAV-mediated miRNA therapy in a
      transgenic model of severe, chronic MD-associated DCM.

PMID- 23963761
TI  - How long does it take to equilibrate the unfolded state of a protein?
AB  - How long does it take to equilibrate the unfolded state of a protein? The answer
      to this question has important implications for our understanding of why many
      small proteins fold with two state kinetics. When the equilibration within the
      unfolded state U is much faster than the folding, the folding kinetics will be
      two state even if there are many folding pathways with different barriers. Yet
      the mean first passage times (MFPTs) between different regions of the unfolded
      state can be much longer than the folding time. This seems to imply that the
      equilibration within U is much slower than the folding. In this communication we
      resolve this paradox. We present a formula for estimating the time to equilibrate
      the unfolded state of a protein. We also present a formula for the MFPT to any
      state within U, which is proportional to the average lifetime of that state
      divided by the state population. This relation is valid when the equilibration
      within U is very fast as compared with folding as it often is for small proteins.
      To illustrate the concepts, we apply the formulas to estimate the time to
      equilibrate the unfolded state of Trp-cage and MFPTs within the unfolded state
      based on a Markov State Model using an ultra-long 208 microsecond trajectory of
      the miniprotein to parameterize the model. The time to equilibrate the unfolded
      state of Trp-cage is ~100 ns while the typical MFPTs within U are tens of
      microseconds or longer. 

PMID- 23963762
TI  - Relaxins enhance growth of spontaneous murine breast cancers as well as
      metastatic colonization of the brain.
AB  - Relaxins are known for their tissue remodeling capacity which is also a hallmark
      of cancer progression. However, their role in the latter context is still
      unclear, particularly in breast cancer. In a mouse model with spontaneously
      arising breast cancer due to erbB2-overexpression we show that exposure to
      porcine relaxin results in significantly enhanced tumour growth as compared to
      control animals. This is accompanied by increased serum concentrations of
      progesterone and estradiol as well as elevated expression of the respective
      receptors and the relaxin receptor RXFP1 in the tumour tissue. It is also
      associated with enhanced infiltration by tumour-associated macrophages which are
      known to promote tumour progression. Additionally, we show in an ex vivo model of
      metastatic brain colonization that porcine relaxin as well as human brain
      specific relaxin-3 promotes invasion into the brain tissue and enhance
      interaction of breast cancer cells with the resident brain macrophages, the
      microglia. Relaxin signaling is mediated via RXFP1, since R 3/I5, a specific
      agonist of the relaxin-3 receptor RXFP3 in the brain, does not significantly
      enhance invasion. Taken together, these findings strongly support a role of
      relaxins in the progression of breast cancer where they foster primary tumour
      growth as well as metastatic colonization by direct and indirect means. 

PMID- 23963763
TI  - Pre-treatment of mice with tumor-conditioned media accelerates metastasis to
      lymph nodes and lungs: a new spontaneous breast cancer metastasis model.
AB  - Current spontaneous metastasis models require a long period of observation after
      establishment of primary tumors to see significant metastatic progression. The
      degree of metastasis is not consistent among animals: this is problematic since
      it requires the use of a large number of animals to obtain reliable statistics.
      Here we report that pre-treatment of animals with tumor-conditioned media (TCM)
      consistently accelerates spontaneous metastasis in breast cancer. An inguinal
      breast tumor model facilitated by TCM showed robust anterior metastasis to the
      axillary and brachial lymph nodes (LN), and the lungs compared to the serum-free
      media treated group. The LN in TCM-treated animals showed enhanced angiogenesis
      and lymphangiogenesis. Primary tumors and lungs in TCM-treated animals showed
      enhanced lymphangiogenesis with no significant change in angiogenesis. TCM
      treated animals also showed metastatic dissemination to abdomen from the primary
      injection site: this would generally enhance metastasis to other organs. In sum,
      the addition of TCM pre-treatment to current metastasis models results in
      accelerated and robust metastasis which would enable more efficient evaluation of
      anti-metastatic agents. 

PMID- 23963764
TI  - Detection and genetic characterization of feline kobuviruses.
AB  - In order to survey for feline kobuviruses infection, fecal samples (n = 39) of
      cats with diarrhea were collected during 2011-2012. Six (14.5%) of the fecal
      samples tested were positive for feline kobuviruses. The partial nucleotide
      sequences of feline kobuviruses based on the RNA-dependent RNA polymerase gene
      were compared to those of other species. Feline kobuviruses were most closely
      related to canine kobuvirus in terms of their amino acid and nucleotide levels.
      In a phylogenetic tree, feline kobuviruses were also closely clustered with
      canine kobuvirus, Aichi virus (human), and mouse kobuvirus. This is the first
      report of the detection and genetic characterization of feline kobuviruses.

PMID- 23963765
TI  - Molecular identification of Ageratum enation virus, betasatellite and
      alphasatellite molecules isolated from yellow vein diseased Amaranthus cruentus
      in India.
AB  - Natural occurrence of yellow vein disease on Amaranthus cruentus was observed at
      Lucknow, India in the year 2008. The causal virus was successfully transmitted
      through whiteflies (Bemisia tabaci) from diseased A. cruentus to healthy
      seedlings of A. cruentus and other test species which indicated begomovirus
      infection. The begomovirus DNA-A, betasatellite, and alphasatellite components
      associated with yellow vein disease were amplified by rolling circle
      amplification using O-29 DNA polymerase from diseased A. cruentus and
      characterized by their sequence analyses. The begomovirus DNA-A genome contained
      six ORFs: AV2 and AV1 in virion sense and AC3, AC2, AC1, and AC4 in complementary
      sense strand; and a non-translated intergenic region having the conserved
      geminiviral nonanucleotide sequence. The virus isolate showed 97-99% sequence
      identities and close phylogenetic relationships with various isolates of Ageratum
      enation virus (AgEV); therefore, the isolate under study was identified as AgEV.
      The beta- and alphasatellite molecules were also identified to be associated with
      the disease based on their high sequence identities and close phylogenetic
      relationships with the respective molecules reported worldwide. Co-infiltration
      of agro-infectious clones of AgEV DNA-A and its betasatellite DNA induced leaf
      curl and enation symptoms after 25-35 days on A. cruentus, Nicotiana benthamiana,
      and N. glutinosa plants. We report the association of AgEV, betasatellite and
      alphasatellite components with yellow vein disease of A. cruentus from India.

PMID- 23963766
TI  - Cyanoacrylate microbial sealants for skin preparation prior to surgery.
AB  - BACKGROUND: Surgical site infections (i.e. incisions that become infected) are a
      continuing concern in health care. Microbial sealant is a liquid that can be
      applied to the skin immediately before surgery and is thought to help reduce the
      incidence of surgical site infections (SSIs) by sealing in the skin flora, thus
      preventing contamination and infection of the surgical site. OBJECTIVES: To
      assess the effects of the preoperative application of microbial sealants
      (compared with no microbial sealant) on rates of SSI in people undergoing clean
      surgery. SEARCH METHODS: For this first update we searched the following
      electronic databases in July 2013: the Cochrane Wounds Group Specialised
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid
      MEDLINE, Ovid MEDLINE - In-Process & Other Non-Indexed Citations, Ovid EMBASE and
      EBSCO CINAHL. SELECTION CRITERIA: Randomised controlled trials (RCTs) were
      eligible for inclusion if they involved people undergoing clean surgery (i.e.
      surgery that does not involve the breathing system, gut, genital or urinary tract
      or any part of the body with an existing infection) in an operating theatre and
      compared the use of preoperative microbial sealants with no microbial sealant.
      DATA COLLECTION AND ANALYSIS: All review authors independently extracted data on
      the characteristics, risk of bias and outcomes of the eligible trials. MAIN
      RESULTS: Three trials (524 participants undergoing clean surgery) met the
      inclusion criteria. The trials all compared cyanoacrylate microbial sealant with
      no sealant, and, when pooled, we found there were fewer SSIs with the use of
      microbial sealant (10/261 participants) than with the control comparison (29/274
      participants). The difference between the two groups was statistically
      significant (risk ratio (RR) 0.36, 95% CI 0.18 to 0.72) but given the number of
      participants and quality of the studies, they should be treated with caution.
      There were some adverse events in one study, but these were not judged to be a
      result of the use of microbial sealant. AUTHORS' CONCLUSIONS: In this first
      update there is still insufficient evidence available to determine whether the
      use of microbial sealants reduces the risk of surgical site infection or not.
      Further rigorous, adequately-powered RCTs are required to investigate this
      properly.

PMID- 23963767
TI  - Chemometric evaluation of near infrared, fourier transform infrared, and Raman
      spectroscopic models for the prediction of nimodipine polymorphs.
AB  - The objective of this study was to assess the performance of the chemometric
      model to predict the proportion of the recrystallized polymorphs of nimodipine
      from the cosolvent formulations. Ranging from 100% to 0% (w/w) of polymorph I,
      the two polymorphs mixtures were prepared and characterized spectroscopically
      using Fourier transformed infrared spectroscopy (FTIR), near-infrared
      spectroscopy (NIR), and Raman spectroscopy. Instrumental responses were treated
      to construct multivariate calibration model using principal component regression
      (PCR) and partial least square regression approaches. Treated data showed better
      model fitting than without treatment, which demonstrated higher correlation
      coefficient (R(2) ) and lower root mean square of standard error (RMSE) and
      standard error (SE). Multiple scattering correction and standard normal variate
      exhibited higher R(2) and lower RMSE and SE values than second derivative.
      Goodness of fit for FTIR and NIR (R(2) ~ 0.99) data was better than Raman (R(2) ~
      0.95). Furthermore, the models were applied on the recrystallized polymorphs
      obtained by storing nimodipine-cosolvent formulations at selected stability
      conditions. The relative composition of the polymorphs differed with storage
      conditions. NIR-chemical imaging on recrystallized sample of nimodipine at 15
      degrees C qualitatively corroborated the model-based prediction of the two
      polymorphs. Therefore, these studies strongly suggest the importance of the
      potential utility of the chemometric model in predicting nimodipine polymorphs.

PMID- 23963768
TI  - A review of topical high-concentration L-menthol as a translational model of cold
      allodynia and hyperalgesia.
AB  - BACKGROUND: Cold allodynia and cold hyperalgesia are both elusive features of
      neuropathic pain, particularly in patients with various polyneuropathies.
      Numerous studies have suggested that topical application of L-menthol causes
      temporary cold hypersensitivity and thus acts as a proxy for associated symptoms.
      This review summarizes studies on L-menthol-induced nociception, cold allodynia
      and cold hyperalgesia in vitro, in animals and in humans. METHODS: A
      comprehensive literature search was performed using the PubMed and Google Scholar
      databases until February 2013. Obtained manuscripts were reviewed for relevancy
      and reference lists of the retrieved articles were cross-checked for additional
      important studies. Solely the literature regarding topical application of L
      menthol in humans was attained systematically. Of the total identified studies
      (96), 10 met the inclusion criteria being controlled studies applying L-menthol
      at a concentration of >= 30%. RESULTS: The extracted data are meticulously
      compared and presented with emphasis on clarity and transparency. In seven animal
      studies, cold allodynia or hyperalgesia was successfully established utilizing
      various methods. Eight studies in healthy volunteers unanimously reported a
      significant increase in cold pain threshold, representing cold allodynia and
      increased supra-threshold cold pain sensitivity, thus demonstrating cold
      hyperalgesia. CONCLUSIONS: Topical high-concentration L-menthol consistently
      induces cold hypersensitivity in animals and humans, thus constituting a
      predictable surrogate model of cold allodynia and hyperalgesia. Understanding
      translational features of this model and its underlying mechanisms could be
      valuable in preclinical and human phases of drug development and in improving
      current treatment of patients with polyneuropathy.

PMID- 23963769
TI  - Improving the transition of highly complex patients into the community: impact of
      a pharmacist in an allogeneic stem cell transplant (SCT) outpatient clinic.
AB  - PURPOSE: Patients having undergone allogeneic stem cell transplantation (SCT)
      require complex medication regimens. To ensure the safe and effective management
      of this patient group, specialised care in a centre with a dedicated and
      experienced healthcare team is essential. The aim of this study was to evaluate
      the effectiveness of a specialty clinical pharmacist working in an ambulatory SCT
      clinic. METHODS: A prospective cohort study was conducted on patients post SCT
      and discharged to the ambulatory setting. Patients were reviewed by a clinical
      pharmacist weekly for six visits. At these visits a medication review was
      undertaken. Interventions from these reviews were recorded. Interventions were
      then assigned a risk rating by a multidisciplinary panel. Adherence was also
      assessed by a Morisky questionnaire and review of dose administration aids.
      Comparison of data over the six-visit period was undertaken. RESULTS: In total 23
      patients were enrolled in the study. All six visits were completed in 17 patients
      and 161 interventions were recorded at an average of 1.4 interventions per
      patient visit. The panel rated 40 % of interventions as high risk, 46 % as medium
      risk and 14 % as low risk. At all visit points high- and medium-risk
      interventions constituted >80 % of the total. Morisky scores improved by an
      average of 1.53 (p < 0.0001) between visits 1 and 6. All patients were scored as
      highly adherent by visit 6. CONCLUSIONS: A specialist clinical pharmacist in the
      SCT outpatient clinic resulted in regular and effective intervention contributing
      to improved medication management and adherence.

PMID- 23963770
TI  - FTO genetic variants and risk of obesity and type 2 diabetes: a meta-analysis of
      28,394 Indians.
AB  - OBJECTIVE: To investigate the magnitude of association of FTO variants with
      obesity, type 2 diabetes (T2DM), and related traits among Asian Indians. METHODS:
      Random-effect meta-analysis was performed on pooled data from eight studies (n =
      28,394) for obesity and related traits and six studies (n = 24,987) for
      assessment of T2DM risk in Indians where FTO variants were reported. RESULTS: The
      minor A-allele of the FTO variant rs9939609 was associated with increased risk of
      obesity (OR 1.15, 95% CI 1.08-1.21, p = 2.14 * 10(-) (5) ), BMI (beta = 0.30
      kg/m2, 95% CI 0.21-0.38, p = 4.78 * 10(-) (11) ) and other regional adiposity
      measurements [waist (beta = 0.74 cm, 95% CI 0.49-0.99), HC (beta = 0.52, 95% CI
      0.26-0.78), and waist-hip ratio (WHR) (beta = 0.002, 95% CI 0.001-0.004)] in
      Indians (p <= 0.001). An increased risk for T2DM (OR 1.11; 95% CI 1.04-1.19, p =
      0.002) was observed, which attenuated when adjusted for age, gender, and BMI (OR
      1.09; 95%CI 1.02-1.16, p = 0.01). CONCLUSIONS: Our study provides evidence of
      association between common FTO variant and obesity risk among Indians with
      comparable effect sizes as in Caucasians. The attenuation of FTO-T2DM risk on BMI
      adjustment reinforces that BMI does not fully account for the adiposity effects
      among Asian Indians who are more centrally obese.

PMID- 23963771
TI  - Color manipulation of mechanoluminescence from stress-activated composite films.
AB  - The prospective application of luminescence to imaging devices is shown using a
      combination of color-tunable and patternable mechanoluminescent materials. A
      white light source is demonstrated by using an alternative color tuning method,
      induced under high vibration conditions. As the implementation is fairly
      straightforward, it is expected that the present results will find a number of
      potential uses in current industrial applications. 

PMID- 23963772
TI  - Expression of recombinant carcinoembryonic-antigen-human-beta-defensin-2 gene in
      colon cancer HCT116 cells.
AB  - The objective of this study was to construct a system driving high expression of
      human-beta-denfensin-2 (HBD-2) system in eukaryotic cell. To construct
      recombinant retrovirus expression vector, CEA signal peptide-HBD-2 (mature
      peptide sequence) was cloned in the retrovirus expression vector PLNCX2. The
      retroviral vector was transfected into PT67 cells by DOTAP; after screening and
      amplifying single clone cell by G418, the virus particles were collected and
      infected to eukaryotic, colon cancer HCT116 cells. Furthermore, the HCT116 cells
      were also screened by using G418 and the resistance clones were obtained.
      Finally, the expression of HBD-2 was detected by Western blotting, which
      suggested a high level of expression of HBD-2 in HCT116 cells. In conclusion, the
      results indicate that high level of HBD-2 expression was obtained in HCT116 cells
      which will help in effective commercial production and purification of HBD-2
      protein. 

PMID- 23963773
TI  - Quantitative assessment of the association between +61A>G polymorphism of
      epidermal growth factor gene and susceptibility to glioma.
AB  - Numerous studies have investigated the risk of cancer associated with the
      polymorphism of epidermal growth factor (EGF) 61A>G, but results have been
      inconsistent. We performed this meta-analysis to drive a more precise estimation
      of the association between this polymorphism and risk of glioma. A comprehensive
      search was conducted to identify all case-control studies on the EGF +61A>G
      polymorphism and glioma risk. Odds ratios (ORs) and 95% confidence intervals (95%
      CIs) were calculated to assess the strength of the association. Statistical
      analysis was performed with the software program Stata (version 12.0). A total of
      ten eligible studies, including 1,888 cases and 2,836 controls were included in
      this work. Overall, there was a significant association between EGF +61A>G
      polymorphism and glioma risk in the allele model (OR = 1.419, 95% CI = 1.144
      1.759, P = 0.001). In the subgroup analysis by ethnicity, significant
      associations were also found in Asian populations under all different genetic
      models (homozygote model: OR = 1.727, 95% CI = 1.310-2.275, P = 0.000;
      heterozygote model: OR = 1.202, 95% CI = 1.023-1.413, P = 0.025; dominant model:
      OR = 1.279, 95% CI = 1.096-1.491, P = 0.002; recessive model: OR = 1.590, 95% CI
      = 1.221-2.070, P = 0.001; and A-allele versus G-allele OR = 1.600, 95% CI = 1.145
      2.236, P = 0.006). However, no significant associations were found among
      Caucasians in all comparison models. In conclusion, the results suggest that
      there is a significant association between EGF +61A>G polymorphism and glioma
      risk among Asians.

PMID- 23963774
TI  - Evaluation of the estimated continuous cardiac output monitoring system in adults
      and children undergoing kidney transplant surgery: a pilot study.
AB  - Evaluation of the estimated continuous cardiac output (esCCO) allows non-invasive
      and continuous assessment of cardiac output. However, the applicability of this
      approach in children has not been assessed thus far. We compared the correlation
      coefficient, bias, standard deviation (SD), and the lower and upper 95 % limits
      of agreement for esCCO and dye densitography-cardiac output (DDG-CO) measurements
      by pulse dye densitometry (PDD) in adults and children. On the basis of these
      assessments, we aimed to examine whether esCCO can be used in pediatric patients.
      DDG-CO was measured by pulse dye densitometry (PDD) using indocyanine green.
      Modified-pulse wave transit time, obtained using pulse oximetry and
      electrocardiography, was used to measure esCCO. Correlations between DDG-CO and
      esCCO in adults and children were analyzed using regression analysis with the
      least squares method. Differences between the two correlation coefficients were
      statistically analyzed using a correlation coefficient test. Bland-Altman plots
      were used to evaluate bias and SD for DDG-CO and esCCO in both adults and
      children, and 95 % limits of agreement (bias +/- 1.96 SD) and percentage error
      (1.96 SD/mean DDG-CO) were calculated and compared. The average age of the adult
      patients (n = 10) was 39.3 +/- 12.1 years, while the average age of the pediatric
      patients (n = 7) was 9.4 +/- 3.1 years (p < 0.001). For adults, the correlation
      coefficient was 0.756; bias, -0.258 L/min; SD, 1.583 L/min; lower and upper 95 %
      limits of agreement for DDG-CO and esCCO, -3.360 and 2.844 L/min, respectively;
      and percentage error, 42.7 %. For children, the corresponding values were 0.904; 
      0.270; 0.908; -2.051 and 1.510 L/min, respectively; and 35.7 %. Due to the high
      percentage error values, we could not establish a correlation between esCCO and
      DDG-CO. However, the 95 % limits of agreement and percentage error were better in
      children than in adults. Due to the high percentage error, we could not confirm a
      correlation between esCCO and DDG-CO. However, the agreement between esCCO and
      DDG-CO seems to be higher in children than in adults. These results suggest that
      esCCO can also be used in children. Future studies with bigger study populations
      will be required to further investigate these conclusions.

PMID- 23963775
TI  - Third-party ATP sensing in polymersomes: a label-free assay of enzyme reactions
      in vesicular compartments.

PMID- 23963776
TI  - Smoking cessation interventions for smokers with current or past depression.
AB  - BACKGROUND: Individuals with current or past depression are often smokers who are
      more nicotine dependent, more likely to suffer from negative mood changes after
      nicotine withdrawal, and more likely to relapse to smoking after quitting than
      the general population, which contributes to their higher morbidity and mortality
      from smoking-related illnesses. It remains unclear what interventions can help
      them to quit smoking. OBJECTIVES: To evaluate the effectiveness of smoking
      cessation interventions, with and without specific mood management components, in
      smokers with current or past depression. SEARCH METHODS: In April 2013, we
      searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,
      EMBASE, PsycINFO, other reviews, and asked experts for information on trials.
      SELECTION CRITERIA: Criteria for including studies in this review were that they
      had to be randomised controlled trials (RCTs) comparing smoking cessation
      interventions in adult smokers with current or past depression. Depression was
      defined as major depression or depressive symptoms. We included studies where
      subgroups of participants with depression were identified, either pre-stated or
      post hoc. The outcome was abstinence from smoking after six months or longer
      follow-up. We preferred prolonged or continuous abstinence and biochemically
      validated abstinence where available. DATA COLLECTION AND ANALYSIS: When
      possible, we estimated pooled risk ratios (RRs) with the Mantel-Haenszel method
      (fixed-effect model). We also performed subgroup analyses, by length of follow
      up, depression measurement, depression group in study, antidepressant use,
      published or unpublished data, format of intervention, level of behavioural
      support, additional pharmacotherapy, type of antidepressant medication, and
      additional nicotine replacement therapy (NRT). MAIN RESULTS: Forty-nine RCTs were
      included of which 33 trials investigated smoking cessation interventions with
      specific mood management components for depression. In smokers with current
      depression, meta-analysis showed a significant positive effect for adding
      psychosocial mood management to a standard smoking cessation intervention when
      compared with standard smoking cessation intervention alone (11 trials, N = 1844,
      RR 1.47, 95% CI 1.13 to 1.92). In smokers with past depression we found a similar
      effect (13 trials, N = 1496, RR 1.41, 95% CI 1.13 to 1.77). Meta-analysis
      resulted in a positive effect, although not significant, for adding bupropion
      compared with placebo in smokers with current depression (5 trials, N = 410, RR
      1.37, 95% CI 0.83 to 2.27). There were not enough trial data to evaluate the
      effectiveness of fluoxetine and paroxetine for smokers with current depression.
      Bupropion (4 trials, N = 404, RR 2.04, 95% CI 1.31 to 3.18) might significantly
      increase long-term cessation among smokers with past depression when compared
      with placebo, but the evidence for bupropion is relatively weak due to the small
      number of studies and the post hoc subgroups for all the studies. There were not
      enough trial data to evaluate the effectiveness of fluoxetine, nortriptyline,
      paroxetine, selegiline, and sertraline in smokers with past depression.Twenty
      three of the 49 trials investigated smoking cessation interventions without
      specific components for depression. There was heterogeneity between the trials
      which compared psychosocial interventions with standard smoking cessation
      counselling for both smokers with current and past depression. Therefore, we did
      not estimate a pooled effect. One trial compared nicotine replacement therapy
      (NRT) versus placebo in smokers with current depression and found a positive,
      although not significant, effect (N = 196, RR 2.64, 95% CI 0.93 to 7.45). Meta
      analysis also found a positive, although not significant, effect for NRT versus
      placebo in smokers with past depression (3 trials, N = 432, RR 1.17, 95% CI 0.85
      to 1.60). Three trials compared other pharmacotherapy versus placebo and six
      trials compared other interventions in smokers with current or past depression.
      Due to heterogeneity between the interventions of the included trials we did not
      estimate pooled effects. AUTHORS' CONCLUSIONS: Evidence suggests that adding a
      psychosocial mood management component to a standard smoking cessation
      intervention increases long-term cessation rates in smokers with both current and
      past depression when compared with the standard intervention alone. Pooled
      results from four trials suggest that use of bupropion may increase long-term
      cessation in smokers with past depression. There was no evidence found for the
      use of bupropion in smokers with current depression. There was not enough
      evidence to evaluate the effectiveness of the other antidepressants in smokers
      with current or past depression. There was also not enough evidence to evaluate
      the group of trials that investigated interventions without specific mood
      management components for depression, including NRT and psychosocial
      interventions.

PMID- 23963777
TI  - Olanzapine solvates.
AB  - Olanzapine was crystallized from 12 organic solvents alone or in mixture, by
      cooling in the freezer, by slow evaporation of the solvent, or by suspending
      olanzapine powder for some time in the solvent. All the samples thus obtained
      were examined by thermal analysis (differential scanning calorimetry-DSC and
      thermogravimetry-TG) to certify the formation of a solvate, the presence of
      polymorph (form 1 or 2) in the desolvated olanzapine, comparing the different
      profile of the thermograms, and to calculate the stoichiometry of the possible
      solvate. According to the DSC thermogram, the solvents can be divided into four
      classes: those that do not form solvates and leave olanzapine form 1 (ethyl
      acetate, toluene, diethyl ether, and acetone); those that form solvate and leave
      form 1 of olanzapine after desolvation (methanol, 1- and 2-propanol); those that
      after desolvation of the solvate show a polymorph transition in the thermogram
      indicating the presence of form 2 of olanzapine (ethanol); other solvents
      (tetrahydrofuran, chloroform, acetonitrile) give solvate thermograms, where this
      last thermal trace is only poorly evident. With few exceptions, each solvent
      forms solvate both when pure and in mixture (10%, v/v, in ethyl acetate).
      Methanol monosolvate displays complex thermogram and thermogravimetric
      desolvation profiles, depending on the crystallization experimental conditions,
      used to prepare the solvates. Dichloromethane solvate was found by X-ray
      diffraction analysis to be amorphous and, on heating during DSC analysis, allowed
      the crystallization of both form 1 and 2, with different weight ratio, according
      to the experimental conditions of the solvate preparation.

PMID- 23963778
TI  - Electrophilic and reactive oxygen species detoxification potentials of chalcone
      dimers is mediated by redox transcription factor Nrf-2.
AB  - Nuclear erythroid related factor-2 (Nrf2), a redox-transcription factor, plays a
      critical role in the detoxification of electrophilic and reactive oxygen species
      that halt various biochemical and molecular processes. This makes it a candidate
      for regulation by polyphenols. This study investigates the capability of chalcone
      dimers (lophirones B and C) to induce expressions and activities of
      cytoprotective enzymes. Chalcone dimers administration to rats not only induced
      the Nrf2, but also suppressed cytoplasmic Kelch-like ECH-associated protein 1
      (Keap1) expressions. In addition, the chalcone dimers significantly (p < 0.05)
      increased the expressions and activities of nicotinamide adenine dinucleotide and
      reduced quinone oxidoreductase-1, glutathione-S-transferase, epoxide hydrolase
      and uridyl glucuronosyl transferase in rat liver. Also, activities of superoxide
      dismutase, catalase, glutathione peroxidase, and glutathione reductase in rat
      liver increased significantly (p < 0.05). Overall, lophirones B and C increased
      the expressions and activities of cytoprotective proteins in rat liver possibly
      through the reduction of cytoplasmic Keap1 expression, leading to the nuclear
      translocation of Nrf2. 

PMID- 23963779
TI  - Diazepam treatment blocks the elevation of hippocampal activity and the
      accelerated proliferation of hippocampal neural stem cells after focal cerebral
      ischemia in mice.
AB  - Hippocampal neurogenesis is accelerated during the elevation of hippocampal
      neural activities under both physiological and pathophysiological conditions. One
      of these conditions, middle cerebral artery occlusion (MCAO), induces both the
      hyperactivities of hippocampal network and the elevation of neural stem cell
      (NSC) proliferation. However, the causal relationship between the elevated
      activity and the elevation of NSC proliferation is still unclear. In this study,
      to block the elevation of hippocampal activity after MCAO in mice, we utilized a
      typical gamma-aminobutyric acid type A (GABAA ) receptor active modulator,
      diazepam. With MCAO mice treated with diazepam, we observed complete
      disappearance of the elevation of hippocampal activity. Additionally, the
      diazepam treatment blocked the elevation of NSC proliferation after MCAO. From
      this result, it is speculated that the increased NSC proliferation is blocked by
      the suppression of elevated neural activity. However, diazepam might have effects
      other than the suppression of hippocampal activity, so we performed additional
      experiment and found that diazepam did not affect the number of bromodeoxyuridine
      positive cells under the normal condition, whereas the GABA agonist pentobarbital
      stimulated NSC/neural progenitor cell proliferation and differentiation. Next, we
      evaluated the expression of the diazepam-binding inhibitor (DBI) protein and
      found that the cells expressed DBI in soma and on the surface of cell membrane.
      From these observations, we can propose that diazepam blocks the elevation of
      hippocampal activity and also NSC proliferation after MCAO.

PMID- 23963780
TI  - Neighborhood environment and physical activity among older women: findings from
      the San Diego Cohort of the women's health initiative.
AB  - BACKGROUND: Few studies of older adults have compared environmental correlates of
      walking and physical activity in women who may be more influenced by the
      environment. Environmental measures at different spatial levels have seldom been
      compared. Findings from previous studies are generally inconsistent. METHODS:
      This study investigated the relationship between the built environment and
      physical activity in older women from the Women's Health Initiative cohort in San
      Diego County (N = 5401). Built environment measures were created for 3 buffers
      around participants' residential address. Linear regression analyses investigated
      the relationship between the built environment features and self-reported
      physical activity and walking. RESULTS: Total walking was significantly
      positively associated with the walkability index (beta = .050: half-mile buffer),
      recreation facility density (beta = .036: 1-mile buffer), and distance to the
      coast (beta = -.064; P-values < .05). Total physical activity was significantly
      negatively associated with distance to the coast and positively with recreation
      facility density (beta = .036: 1-mile buffer; P < .05). CONCLUSIONS: Although
      effect sizes were small, we did find important relationships between walkability
      and walking in older adults, which supports recommendations for community design
      features to include age friendly elements. More intense physical activity may
      occur in recreational settings than neighborhood streets.

PMID- 23963782
TI  - Retention of mandibular advancement devices in the treatment of obstructive sleep
      apnea: an in vitro pilot study.
AB  - PURPOSE: In order for a mandibular advancement device (MAD) to be efficacious, it
      must remain seated on the teeth during sleep. Quantitative data on the retentive
      characteristics of MADs are currently unavailable. The present pilot study is the
      first to describe an in vitro setup testing the retentive characteristics of
      different monobloc MADs. METHODS: A hydraulic cyclic test machine was used with
      MADs seated on dental casts to measure retention forces upon removal of the MADs.
      A custom-made monobloc (CM-mono), a thermoplastic monobloc (TP-mono), and a
      thermoplastic duobloc (TP-duo) configured as a monobloc were tested. Two
      protrusions were investigated, representing 25 and 65% of the maximal protrusion.
      The effects of the type of MAD, duration of the test, and amount of protrusion on
      removal forces were measured. RESULTS: The measured removal forces of all three
      MADs tested differed significantly, with the TP-duo showing the highest values (P
      < 0.0001). The effects of wear due to the repetitive cyclic loading became
      obvious by the production of wear particles in all MADs tested. However, only the
      TP-duo showed a significant reduction in time in removal forces for both
      protrusion positions (P < 0.0001; P = 0.0011). The effect of the amount of
      protrusion on the removal forces differed significantly between all three MADs
      tested (P = 0.0074). CONCLUSIONS: This in vitro pilot study reveals significant
      differences in retention forces for the MADs tested. The findings are consistent
      with clinical effects of nightly loss of MADs as reported in the literature and
      are within the range of reported physiological mouth-opening forces. Future
      research is needed to determine the key design features of MADs that explain
      these differences.

PMID- 23963783
TI  - The timing between REM sleep behavior disorder and Parkinson's disease.
AB  - PURPOSE: In Parkinson's disease (PD) patients, REM sleep behavior disorder (RBD)
      might precede PD or develop with or after the onset of PD. No previous study has
      explored differences between these two groups. The aim of this study was
      therefore to compare clinical features and REM sleep chin electromyographic
      patterns between patients in whom RBD heralded PD and those in whom RBD
      occurrence coincided with or followed the clinical manifestations of PD. METHOD:
      Twenty-seven consecutive PD patients (mean age 67.9 years) were enrolled.
      Detailed clinical, laboratory, and polysomnographic studies were obtained in all
      participants. RESULTS: Sixteen of the 27 patients were affected by RBD. These had
      a significantly higher stage of PD and took significantly higher doses of
      dopaminergic therapy; their disease duration tended to be longer, and their
      cognitive status tended to be lower. PD patients in whom RBD preceded PD (n = 6)
      did not differ from PD patients without RBD in disease parameters, while PD
      patients in whom RBD developed with or after PD (n = 10) showed a significantly
      higher disease stage, took significantly higher dopaminergic therapy, and had a
      longer disease duration. CONCLUSION: Our findings are compatible with the
      hypothesis that patients in whom RBD precedes, or does not precede, PD might
      constitute two possibly distinct clinical and physiopathological groups, based on
      different progressive neuropathological sequences of events.

PMID- 23963781
TI  - Protein domain definition should allow for conditional disorder.
AB  - Proteins are often classified in a binary fashion as either structured or
      disordered. However this approach has several deficits. Firstly, protein folding
      is always conditional on the physiochemical environment. A protein which is
      structured in some circumstances will be disordered in others. Secondly, it hides
      a fundamental asymmetry in behavior. While all structured proteins can be
      unfolded through a change in environment, not all disordered proteins have the
      capacity for folding. Failure to accommodate these complexities confuses the
      definition of both protein structural domains and intrinsically disordered
      regions. We illustrate these points with an experimental study of a family of
      small binding domains, drawn from the RNA polymerase of mumps virus and its
      closest relatives. Assessed at face value the domains fall on a structural
      continuum, with folded, partially folded, and near unstructured members. Yet the
      disorder present in the family is conditional, and these closely related
      polypeptides can access the same folded state under appropriate conditions. Any
      heuristic definition of the protein domain emphasizing conformational stability
      divides this domain family in two, in a way that makes no biological sense.
      Structural domains would be better defined by their ability to adopt a specific
      tertiary structure: a structure that may or may not be realized, dependent on the
      circumstances. This explicitly allows for the conditional nature of protein
      folding, and more clearly demarcates structural domains from intrinsically
      disordered regions that may function without folding. 

PMID- 23963785
TI  - TPX2 expression is associated with cell proliferation and patient outcome in
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: The molecular and genetic changes underlying esophageal squamous cell
      carcinoma (ESCC) tumor formation and rapid progression are poorly understood.
      Using high-throughput data analysis, we examined molecular changes involved in
      ESCC pathogenesis and investigated their clinical relevance. METHODS: Five
      independent microarray datasets were examined for differentially expressed genes
      and pathways. For validation, mRNA expression in tumor and matched normal tissues
      from 16 ESCC cases was examined by cDNA microarray, and protein expression in 97
      ESCC specimens was investigated using immunohistochemical stains. The association
      between clinicopathological parameters and the expression of Aurora kinase A
      (Aurora-A) and TPX2 was analyzed. The impact of TPX2 expression was also assessed
      in ESCC cancer cells. RESULTS: AURKA and TPX2, members of the "Role of Ran in
      mitotic spindle regulation" pathway, were selected for further investigation.
      Verification by cDNA microarray showed that both genes were overexpressed in
      tumor tissues, and immunohistochemical staining showed Aurora-A and TPX2
      expression in 88.4 and 90.6 % of ESCC specimens, respectively. High TPX2
      expression was a significant prognosticator for overall and disease-free survival
      in univariate analysis and remained an independent prognostic factor in
      multivariate analysis (HR 1.802, p = 0.037). TPX2 knockdown clones showed
      inhibited cellular proliferation in growth curve studies and formed fewer
      colonies in the clonogenic assay. CONCLUSIONS: Using bioinformatics resources,
      which were validated by microarray analysis and immunohistochemistry stains, and
      manipulation of TPX2 expression in ESCC cell lines, we demonstrated that TPX2
      expression is associated with cell proliferation and poor prognosis among
      patients with resected ESCC.

PMID- 23963786
TI  - Effect of an 18-month physical activity and weight loss intervention on body
      composition in overweight and obese older adults.
AB  - OBJECTIVE: Our primary objective was to determine the long-term effects of
      physical activity (PA) and weight loss (WL) on body composition in
      overweight/obese older adults. Secondarily, the association between change in
      body mass and composition on change in several cardiometabolic risk factors and
      mobility was evaluated. DESIGN AND METHODS: 288 older (X +/- SD: 67.0 +/- 4.8
      years), overweight/obese (BMI 32.8 +/- 3.8 kg/m2 ) men and women participated in
      this 18-month randomized, controlled trial. Treatment groups included PA + WL (n
      = 98), PA-only (n = 97), and a successful aging (SA) health education control (n
      = 93). DXA-acquired body composition measures (total body fat and lean mass),
      conventional biomarkers of cardiometabolic risk, and 400-m walk time were
      obtained at baseline and 18 months. RESULTS: Fat mass was significantly reduced
      from (X +/- SE) 36.5 +/- 8.9 kg to 31.7 +/- 9.0 kg in the PA + WL group (p <
      0.01), but remained unchanged from baseline in the PA-only (-0.8 +/- 3.8 kg) and
      SA (-0.0 +/- 3.9 kg) group. Lean mass losses were three times greater in the PA +
      WL groups compared to PA-only or SA groups (-2.5 +/- 2.8 kg vs. -0.7 +/- 2.2 kg
      or -0.8 +/- 2.4 kg, respectively; p < 0.01); yet due to a larger decrease in fat
      mass, percent lean mass was significantly increased over baseline in the PA + WL
      groups (2.1% +/- 2.6%; p < 0.01). Fat mass loss was primarily responsible for WL
      associated improvements in cardiometabolic risk factors, while reduction in body
      weight, regardless of compartment, was significantly associated with improved
      mobility. CONCLUSION: This 18-month PA + WL program resulted in a significant
      reduction in percent body fat with a concomitant increase in percent body lean
      mass. Shifts in body weight and composition were associated with favorable
      changes in clinical parameters of cardiometabolic risk and mobility. Moderate PA
      without WL had no effect on body composition.

PMID- 23963787
TI  - Complex multilocus effects of catechol-O-methyltransferase haplotypes predict
      pain and pain interference 6 weeks after motor vehicle collision.
AB  - Catechol-O-methyltransferase, encoded by COMT gene, is the primary enzyme that
      metabolizes catecholamines. COMT haplotypes have been associated with
      vulnerability to persistent non-traumatic pain. In this prospective observational
      study, we investigated the influence of COMT on persistent pain and pain
      interference with life functions after motor vehicle collision (MVC) in 859
      European American adults for whom overall pain (0-10 numeric rating scale) and
      pain interference (Brief Pain Inventory) were assessed at week 6 after MVC. Ten
      single nucleotide polymorphisms spanning the COMT gene were successfully
      genotyped, and nine were present in three haploblocks: block 1 (rs2020917,
      rs737865, rs1544325), block 2 (rs4633, rs4818, rs4680, rs165774), and block 3
      (rs174697, rs165599). After adjustment for multiple comparisons, haplotype TCG
      from block 1 predicted decreased pain interference (p = 0.004). The pain
      protective effect of the low pain sensitivity (CGGG) haplotype from block 2 was
      only observed if at least one TCG haplotype was present in block 1 (haplotype *
      haplotype interaction p = 0.002 and <0.0001 for pain and pain interference,
      respectively). Haplotype AG from block 3 was associated with pain and
      interference in males only (sex * haplotype interaction p = 0.005 and 0.0005,
      respectively). These results suggest that genetic variants in the distal promoter
      are important contributors to the development of persistent pain after MVC,
      directly and via the interaction with haplotypes in the coding region of the
      gene. 

PMID- 23963788
TI  - Epigenetics and the modulation of neuroinflammation.
AB  - Innate immune responses in the central nervous system (CNS) have key roles
      influencing both physiological and pathological processes. Microglia are innate
      immune effector cells that reside within the CNS. These inflammatory cells are
      constantly surveying their external environment and rapidly respond to a variety
      of molecules that signal changes in CNS homeostasis. In response to these
      signals, microglia influence neuronal connections, modulate the functions of
      other glia, and mediate inflammatory responses to disease or injury. In parallel
      with the regulation of inflammatory responses outside of the CNS, investigators
      have observed that microglia are capable of heterogeneous responses to exogenous
      and endogenous signals. While much of this molecular and morphological
      heterogeneity is regulated by gene transcription, there is ample evidence that
      microglial behavior is determined, in part, by epigenetic regulation. Recent work
      has demonstrated that processes involving DNA methylation, histone modification,
      and noncoding RNAs also have important roles in modulating neuroinflammation.
      Here I will review the evidence supporting a role for epigenetic regulation of
      neuroinflammation and describe how this might influence the outcome of several
      CNS disorders, including addiction, infection, multiple sclerosis, and stroke. 

PMID- 23963790
TI  - Moderating black powder chemistry for the synthesis of doped and highly porous
      graphene nanoplatelets and their use in electrocatalysis.
AB  - Inspired by black powder explosion, a mixture of sugar and nitrate is diluted
      with inert molten salt, such that their rapid reaction is moderated, allowing
      capturing of the intermediacy product: highly porous N-doped graphene nanoplates.
      The methodology is extended to S-doped porous carbon sheets by replacing the
      nitrate with sulfate. These MS-derived carbons show promising performances
      towards electrocatalysis and capacitive energy storage. 

PMID- 23963789
TI  - Development of inducible leucine-rich repeat kinase 2 (LRRK2) cell lines for
      therapeutics development in Parkinson's disease.
AB  - The pathogenic mechanism(s) contributing to loss of dopamine neurons in
      Parkinson's disease (PD) remain obscure. Leucine-rich repeat kinase 2 (LRRK2)
      mutations are linked, as a causative gene, to PD. LRRK2 mutations are estimated
      to account for 10% of familial and between 1 % and 3 % of sporadic PD. LRRK2
      proximate single nucleotide polymorphisms have also been significantly associated
      with idiopathic/sporadic PD by genome-wide association studies. LRRK2 is a
      multidomain-containing protein and belongs to the protein kinase super-family. We
      constructed two inducible dopaminergic cell lines expressing either human-LRRK2
      wild-type or human-LRRK2-mutant (G2019S). Phenotypes of these LRRK2 cell lines
      were examined with respect to cell viability, morphology, and protein function
      with or without induction of LRRK2 gene expression. The overexpression of G2019S
      gene promoted (1) low cellular metabolic activity without affecting cell
      viability, (2) blunted neurite extension, and (3) increased phosphorylation at
      S910 and S935. Our observations are consistent with reported general phenotypes
      in LRRK2 cell lines by other investigators. We used these cell lines to
      interrogate the biological function of LRRK2, to evaluate their potential as a
      drug-screening tool, and to investigate screening for small hairpin RNA-mediated
      LRRK2 G2019S gene knockdown as a potential therapeutic strategy. A proposed LRRK2
      kinase inhibitor (i.e., IN-1) decreased LRRK2 S910 and S935 phosphorylation in
      our MN9DLRRK2 cell lines in a dose-dependent manner. Lentivirus-mediated transfer
      of LRRK2 G2019S allele-specific small hairpin RNA reversed the blunting of
      neurite extension caused by LRRK2 G2019S overexpression. Taken together, these
      inducible LRRK2 cell lines are suitable reagents for LRRK2 functional studies,
      and the screening of potential LRRK2 therapeutics.

PMID- 23963791
TI  - Sex influences the effect of body mass index on the vascular response to
      angiotensin II in humans.
AB  - OBJECTIVE: Sex influences the cardiorenal risk associated with body mass index
      (BMI). The role of the renin-angiotensin-aldosterone system in adiposity-mediated
      cardiorenal risk profiles in healthy, non-obese men and women was investigated.
      METHODS: Systemic and renal hemodynamic responses to angiotensin-II (AngII) as a
      function of BMI, waist and hip circumference, waist-hip ratio, as well as fat and
      lean mass were measured in 18 men and 25 women in high-salt balance, stratified
      by BMI (<25 kg/m2 (ideal body weight (IBW)) vs. >=25 kg/m2 overweight)). RESULTS:
      In men (n = 7, BMI 23 +/- 1 kg/m2) and women (n = 14, BMI 22 +/- 2 kg/m2) of IBW,
      BMI was not associated with the systolic blood pressure (SBP) response to AngII.
      In contrast, overweight men (n = 11, 29 +/- 2 kg/m2) demonstrated a progressively
      more blunted vasoconstrictor SBP response to AngII challenge as BMI increased (P
      = 0.007), even after adjustment for covariates. Women maintained the same
      relationship between BMI and the SBP response to AngII irrespective of weight
      status (P = 0.2, IBW vs. overweight women). Compared to BMI, other adiposity
      measures showed similar associations to systemic AngII responsiveness in men but
      not in women. Increasing BMI was associated with a blunted renovasoconstrictor
      response to AngII in all subjects, but was more pronounced in men. CONCLUSION:
      Sex influences the effect of adiposity on vascular angiotensin-responsiveness.

PMID- 23963792
TI  - Engineered solubility tag for solution NMR of proteins.
AB  - The low solubility of many proteins hinders large scale expression and
      purification as well as biophysical measurements. Here, we devised a general
      strategy to solubilize a protein by conjugating it at a solvent-exposed position
      to a 6 kDa protein that was re-engineered to be highly soluble. We applied this
      method to the CARD domain of Apoptosis-associated speck-like protein containing a
      CARD (ASC), which represents one member of a class of proteins that are
      notoriously prone to aggregation. Attachment of the tag to a cysteine residue,
      introduced by site-directed mutagenesis at its self-association interface,
      improved the solubility of the ASC CARD over 50-fold under physiological
      conditions. Although it is not possible to use nuclear magnetic resonance (NMR)
      to obtain a high quality 2D correlation spectrum of the wild type domain under
      physiological conditions, we demonstrate that NMR relaxation parameters of the
      solubilized variant are sufficiently improved to facilitate virtually any
      demanding measurement. The method shown here represents a straightforward
      approach for dramatically increasing protein solubility, enabled by ease of
      labeling as well as flexibility in tag placement with minimal perturbation to the
      target.

PMID- 23963793
TI  - Desferrioxamine mesylate for managing transfusional iron overload in people with
      transfusion-dependent thalassaemia.
AB  - BACKGROUND: Thalassaemia major is a genetic disease characterised by a reduced
      ability to produce haemoglobin. Management of the resulting anaemia is through
      red blood cell transfusions.Repeated transfusions result in an excessive
      accumulation of iron in the body (iron overload), removal of which is achieved
      through iron chelation therapy. Desferrioxamine mesylate (desferrioxamine) is one
      of the most widely used iron chelators. Substantial data have shown the
      beneficial effects of desferrioxamine, although adherence to desferrioxamine
      therapy is a challenge. Alternative oral iron chelators, deferiprone and
      deferasirox, are now commonly used. Important questions exist about whether
      desferrioxamine, as monotherapy or in combination with an oral iron chelator, is
      the best treatment for iron chelation therapy. OBJECTIVES: To determine the
      effectiveness (dose and method of administration) of desferrioxamine in people
      with transfusion-dependent thalassaemia.To summarise data from trials on the
      clinical efficacy and safety of desferrioxamine for thalassaemia and to compare
      these with deferiprone and deferasirox. SEARCH METHODS: We searched the Cochrane
      Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials
      Register. We also searched MEDLINE, EMBASE, CENTRAL (The Cochrane Library),
      LILACS and other international medical databases, plus ongoing trials registers
      and the Transfusion Evidence Library (www.transfusionevidencelibrary.com). All
      searches were updated to 5 March 2013. SELECTION CRITERIA: Randomised controlled
      trials comparing desferrioxamine with placebo, with another iron chelator, or
      comparing two schedules or doses of desferrioxamine, in people with transfusion
      dependent thalassaemia. DATA COLLECTION AND ANALYSIS: Six authors working
      independently were involved in trial quality assessment and data extraction. For
      one trial, investigators supplied additional data upon request. MAIN RESULTS: A
      total of 22 trials involving 2187 participants (range 11 to 586 people) were
      included. These trials included eight comparisons between desferrioxamine alone
      and deferiprone alone; five comparisons between desferrioxamine combined with
      deferiprone and deferiprone alone; eight comparisons between desferrioxamine
      alone and desferrioxamine combined with deferiprone; two comparisons of
      desferrioxamine with deferasirox; and two comparisons of different routes of
      desferrioxamine administration (bolus versus continuous infusion). Overall, few
      trials measured the same or long-term outcomes. Seven trials reported cardiac
      function or liver fibrosis as measures of end organ damage; none of these
      included a comparison with deferasirox.Five trials reported a total of seven
      deaths; three in patients who received desferrioxamine alone, two in patients who
      received desferrioxamine and deferiprone. A further death occurred in a patient
      who received deferiprone in another who received deferasirox alone. One trial
      reported five further deaths in patients who withdrew from randomised treatment
      (deferiprone with or without desferrioxamine) and switched to desferrioxamine
      alone.One trial planned five years of follow up but was stopped early due to the
      beneficial effects of a reduction in serum ferritin levels in those receiving
      combined desferrioxamine and deferiprone treatment compared with deferiprone
      alone. The results of this and three other trials suggest an advantage of
      combined therapy with desferrioxamine and deferiprone over monotherapy to reduce
      iron stores as measured by serum ferritin. There is, however, no evidence for the
      improved efficacy of combined desferrioxamine and deferiprone therapy against
      monotherapy from direct or indirect measures of liver iron.Earlier trials
      measuring the cardiac iron load indirectly by measurement of the magnetic
      resonance imaging T2* signal had suggested deferiprone may reduce cardiac iron
      more quickly than desferrioxamine. However, meta-analysis of two trials showed a
      significantly lower left ventricular ejection fraction in patients who received
      desferrioxamine alone compared with those who received combination therapy using
      desferrioxamine with deferiprone.Adverse events were recorded by 18 trials. These
      occurred with all treatments, but were significantly less likely with
      desferrioxamine than deferiprone in one trial, relative risk 0.45 (95% confidence
      interval 0.24 to 0.84) and significantly less likely with desferrioxamine alone
      than desferrioxamine combined with deferiprone in two other trials, relative risk
      0.33 (95% confidence interval 0.13 to 0.84). In particular, four studies reported
      permanent treatment withdrawal due to adverse events from deferiprone; only one
      of these reported permanent withdrawals associated with desferrioxamine. Adverse
      events also occurred at a higher frequency in patients who received deferasirox
      than desferrioxamine in one trial. Eight trials reported local adverse reactions
      at the site of desferrioxamine infusion including pain and swelling. Adverse
      events associated with deferiprone included joint pain, gastrointestinal
      disturbance, increases in liver enzymes and neutropenia; adverse events
      associated with deferasirox comprised increases in liver enzymes and renal
      impairment. Regular monitoring of white cell counts has been recommended for
      deferiprone and monitoring of liver and renal function for deferasirox.In
      summary, desferrioxamine and the oral iron chelators deferiprone and deferasirox
      produce significant reductions in iron stores in transfusion-dependent, iron
      overloaded people. There is no evidence from randomised clinical trials to
      suggest that any one of these has a greater reduction of clinically significant
      end organ damage, although in two trials, combination therapy with
      desferrioxamine and deferiprone showed a greater improvement in left ventricular
      ejection fraction than desferrioxamine used alone. AUTHORS' CONCLUSIONS:
      Desferrioxamine is the recommended first-line therapy for iron overload in people
      with thalassaemia major and deferiprone or deferasirox are indicated for treating
      iron overload when desferrioxamine is contraindicated or inadequate. Oral
      deferasirox has been licensed for use in children aged over six years who receive
      frequent blood transfusions and in children aged two to five years who receive
      infrequent blood transfusions. In the absence of randomised controlled trials
      with long-term follow up, there is no compelling evidence to change this
      conclusion.Worsening iron deposition in the myocardium in patients receiving
      desferrioxamine alone would suggest a change of therapy by intensification of
      desferrioxamine treatment or the use of desferrioxamine and deferiprone
      combination therapy.Adverse events are increased in patients treated with
      deferiprone compared with desferrioxamine and in patients treated with combined
      deferiprone and desferrioxamine compared with desferrioxamine alone. People
      treated with all chelators must be kept under close medical supervision and
      treatment with deferiprone or deferasirox requires regular monitoring of
      neutrophil counts or renal function respectively. There is an urgent need for
      adequately-powered, high-quality trials comparing the overall clinical efficacy
      and long-term outcomes of deferiprone, deferasirox and desferrioxamine.

PMID- 23963794
TI  - Oxygen therapy for acute myocardial infarction.
AB  - BACKGROUND: Oxygen (O2) is widely used in people with acute myocardial infarction
      (AMI) although it has been suggested it may do more harm than good. Previous
      systematic reviews have concluded that there was insufficient evidence to know
      whether oxygen reduced, increased or had no effect on heart ischaemia or infarct
      size, as did our original Cochrane review on this topic in 2010. The wide
      dissemination of the lack of evidence to support this widely-used intervention
      since 2010 may stimulate the needed trials of oxygen therapy, and it is therefore
      important that this review is updated regularly. OBJECTIVES: To review the
      evidence from randomised controlled trials to establish whether routine use of
      inhaled oxygen in acute myocardial infarction (AMI) improves patient-centred
      outcomes, in particular pain and death. SEARCH METHODS: The following
      bibliographic databases were searched last in July 2012: the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE (OVID),
      EMBASE (OVID), CINAHL (EBSCO) and Web of Science (ISI). LILACS (Latin American
      and Caribbean Health Sciences Literature) and PASCAL were last searched in May
      2013. We also contacted experts to identify any studies. We applied no language
      restrictions. SELECTION CRITERIA: Randomised controlled trials of people with
      suspected or proven AMI (ST-segment elevation myocardial infarction (STEMI) or
      non-STEMI), less than 24 hours after onset, in which the intervention was inhaled
      oxygen (at normal pressure) compared to air and regardless of cotherapies
      provided these were the same in both arms of the trial. DATA COLLECTION AND
      ANALYSIS: Two authors independently reviewed the titles and abstracts of
      identified studies to see if they met the inclusion criteria, and independently
      undertook the data extraction. The quality of studies and the risk of bias were
      assessed according to guidance in the Cochrane Handbook. The primary outcomes
      were death, pain and complications. The measure of effect used was the risk ratio
      (RR) with a 95% confidence interval (CI). MAIN RESULTS: The updated search
      identified one new trial. In total, four trials involving 430 participants were
      included and 17 deaths occurred. The pooled RR of death was 2.05 (95% CI 0.75 to
      5.58) in an intention-to-treat analysis and 2.11 (95% CI 0.78 to 5.68) in
      participants with confirmed AMI. While suggestive of harm, the small number of
      deaths recorded means that this could be a chance occurrence. Pain was measured
      by analgesic use. The pooled RR for the use of analgesics was 0.97 (95% CI 0.78
      to 1.20). AUTHORS' CONCLUSIONS: There is no conclusive evidence from randomised
      controlled trials to support the routine use of inhaled oxygen in people with
      AMI. A definitive randomised controlled trial is urgently required, given the
      mismatch between trial evidence suggestive of possible harm from routine oxygen
      use and recommendations for its use in clinical practice guidelines.

PMID- 23963795
TI  - Axonal fasciculation and the role of polysialic acid-neural cell adhesion
      molecule in rat cortical neurons.
AB  - Axonal fasciculation is a mechanism deployed by growing axons to reach their
      targets during development of the nervous system. Published data have suggested
      the involvement of neuronal cell adhesion molecules (NCAM) in axonal
      fasciculation. We have characterized the formation of axonal fascicles in serum
      free, primary cultures of cortical neurons from embryonic rat brains. Unlike the
      published data, axonal fascicles in our system have a unique morphology: they are
      waveform, are rarely thicker than 20 MUm, and can reach up to several millimeters
      in length. We observed an age and time dependence in the formation of fascicles.
      They formed only in cultures from embryonic day 15-17 brain and only between 4
      days in vitro (DIV) and 11 DIV. Electron microscopy showed that the fascicles
      consisted of mostly axonal processes. Immunocytochemical staining confirmed that
      the fascicles were positive for the 66-kDa neurofilament protein, NF66, but they
      contained few, if any, microtubule-associated protein-2-positive or glial
      fibrillary acidic protein-positive processes. Polysialic acids appeared to be
      critical in the formation of fascicles. Neuraminidase treatment prevented the
      formation of fascicles when added before 5 DIV. Addition of a specific inhibitor
      blocked the effect of neuraminidase. The cortical neurons in our model shared
      several important features with axon fasciculation in vivo and may provide a
      unique system for studying the molecular mechanisms involved in the formation of
      axonal tracts in the brain.

PMID- 23963796
TI  - Sunitinib combined with pemetrexed and carboplatin in patients with advanced
      solid malignancies--results of a phase I dose-escalation study.
AB  - OBJECTIVES: The maximum tolerated dose (MTD) and overall safety of sunitinib plus
      pemetrexed and carboplatin was determined in patients with advanced solid
      malignancies. METHODS: In this phase I dose-escalation study, patients received
      oral sunitinib on a continuous daily dosing (CDD) schedule (37.5 mg/day) or
      Schedule 2/1 (2 weeks on treatment, 1 week off treatment; 37.5 or 50 mg/day).
      Pemetrexed (400-500 mg/m(2) IV) and carboplatin (AUC = 5 mg.min/ml IV) were
      administered q3w. At the MTD for the chosen schedule, a cohort of patients with
      non-small cell lung cancer (NSCLC) or mesothelioma was further evaluated.
      RESULTS: Twenty-one patients were enrolled on Schedule 2/1 (expansion cohort
      included) and 3 patients on the CDD schedule. The MTD on Schedule 2/1 was
      sunitinib 37.5 mg/day with pemetrexed 500 mg/m(2) and carboplatin AUC = 5
      mg.min/ml; MTD on the CDD schedule was not established. Dose-limiting toxicities
      included grade 3/4 neutropenia, grade 3 thrombocytopenia, and grade 3 hand-foot
      syndrome. The most common grade 3/4 drug-related non-hematologic adverse events
      at Schedule 2/1 MTD were fatigue/asthenia and diarrhea (both n = 4). Grade 3/4
      hematologic abnormalities included neutropenia (83%) and leukopenia (83%).
      Pharmacokinetic data revealed no clinically significant drug-drug interactions.
      Best response at the Schedule 2/1 MTD was stable disease >=8 weeks in 3/5
      evaluable patients (60%). CONCLUSIONS: With this combination, in patients with
      advanced solid malignancies, sunitinib MTD on Schedule 2/1 was 37.5 mg/day.
      Sunitinib plus pemetrexed and carboplatin were tolerable at the MTD, although
      sunitinib dose delays and reductions were often required due to myelosuppression.

PMID- 23963797
TI  - Self-assembly of poly-adenine-tailed CpG oligonucleotide-gold nanoparticle
      nanoconjugates with immunostimulatory activity.
AB  - Synthetic unmethylated cytosine-guanine (CpG) oligodeoxynucleotides (CpG ODNs)
      possess high immunostimulatory activity and have been widely used as a
      therapeutic tool for various diseases including infection, allergies, and cancer.
      A variety of nanocarriers have been developed for intracellular delivery of CpG
      ODNs that are otherwise nonpermeable through the cellular membrane. For example,
      previous studies showed that gold nanoparticles (AuNPs) could efficiently deliver
      synthetic thiolated CpG ODNs into cultured cells and induce expression of
      proinflammatory cytokines. Nevertheless, the necessity of using thiolated CpG
      ODNs for the modification of AuNPs inevitably complicates the synthesis of the
      nanoconjugates and increases the cost. A new approach is demonstrated for facile
      assembly of AuNP-CpG nanoconjugates for cost-effective drug delivery. It is found
      that non-thiolated, diblock ODNs containing a CpG motif and a poly-adenine
      (polyA) tail can readily self-assemble on the surface of AuNPs with controllable
      and tunable density. Such nanoconjugates are efficiently delivered into RAW264.7
      cells and induce immune response in a Toll-like receptor 9 (TLR9)-dependent
      manner. Under optimal conditions, polyA-CpG-AuNPs show significantly higher
      immunostimulatory activity than their thiolated counterpart. In addition, the
      immunostimulatory activity of CpG-AuNPs can be modulated by varying the length of
      the polyA tail. In vivo induction of immune responses in mice is demonstrated by
      using polyA-tailed CpG-AuNP nanoconjugates.

PMID- 23963798
TI  - The chemistry and biology of soluble guanylate cyclase stimulators and
      activators.
AB  - The vasodilatory properties of nitric oxide (NO) have been utilized in
      pharmacotherapy for more than 130 years. Still today, NO-donor drugs are
      important in the management of cardiovascular diseases. However, inhaled NO or
      drugs releasing NO and organic nitrates are associated with noteworthy
      therapeutic shortcomings, including resistance to NO in some disease states, the
      development of tolerance during long-term treatment, and nonspecific effects,
      such as post-translational modification of proteins. The beneficial actions of NO
      are mediated by stimulation of soluble guanylate cyclase (sGC), a heme-containing
      enzyme which produces the intracellular signaling molecule cyclic guanosine
      monophosphate (cGMP). Recently, two classes of compounds have been discovered
      that amplify the function of sGC in a NO-independent manner, the so-called sGC
      stimulators and sGC activators. The most advanced drug, the sGC stimulator
      riociguat, has successfully undergone Phase III clinical trials for different
      forms of pulmonary hypertension.

PMID- 23963799
TI  - Analysis of physical activity mass media campaign design.
AB  - BACKGROUND: Mass media campaigns are a necessary tool for public health
      practitioners to reach large populations and promote healthy behaviors. Most
      health scholars have concluded that mass media can significantly influence the
      health behaviors of populations; however the effects of such campaigns are
      typically modest and may require significant resources. A recent Community
      Preventive Services Task Force review on stand-alone mass media campaigns
      concluded there was insufficient evidence to determine their effectiveness in
      increasing physical activity, partly due to mixed methods and modest and
      inconsistent effects on levels of physical activity. METHODS: A secondary
      analysis was performed on the campaigns evaluated in the Task Force review to
      determine use of campaign-building principles, channels, and levels of awareness
      and their impact on campaign outcomes. Each study was analyzed by 2 reviewers for
      inclusion of campaign building principles. RESULTS: Campaigns that included 5 or
      more campaign principles were more likely to be successful in achieving physical
      activity outcomes. CONCLUSION: Campaign success is more likely if the campaign
      building principles (formative research, audience segmentation, message design,
      channel placement, process evaluation, and theory-based) are used as part of
      campaign design and planning.

PMID- 23963801
TI  - Assessing the breast cancer risk distribution for women undergoing screening in
      British Columbia.
AB  - Breast cancer risk estimations are both informative and useful at the population
      level, with many screening programs relying on these assessments to allocate
      resources such as breast MRI. This cross-sectional multicenter study attempts to
      quantify the breast cancer risk distribution for women between the ages of 40 to
      79 years undergoing screening mammography in British Columbia (BC), Canada. The
      proportion of women at high breast cancer risk was estimated by surveying women
      enrolled in the Screening Mammography Program of British Columbia (SMPBC) for
      known breast cancer risk factors. Each respondent's 10-year risk was computed
      with both the Tyrer-Cuzick and Gail risk assessment models. The resulting risk
      distributions were evaluated using the guidelines from the National Institute for
      Health and Care Excellence (United Kingdom). Of the 4,266 women surveyed, 3.5% of
      women between the ages of 40 to 79 years were found to have a high 10-year risk
      of developing breast cancer using the Tyrer-Cuzick model (1.1% using the Gail
      model). When extrapolated to the screening population, it was estimated that
      19,414 women in the SMPBC are considered to be at high breast cancer risk. These
      women may benefit from additional MRI screening; preliminary analysis suggests
      that 4 to 5 additional MRI machines would be required to screen these high-risk
      women. However, the use of different models and guidelines will modify the number
      of women qualifying for additional screening interventions, thus impacting the
      MRI resources required. The results of this project can now be used to inform
      decision-making groups about resource allocation for breast cancer screening in
      BC.

PMID- 23963800
TI  - Postprandial oxidative stress is modulated by dietary fat in adipose tissue from
      elderly people.
AB  - We have investigated whether dietary fat modifies the postprandial oxidative
      stress in adipose tissue of elderly people. Twenty participants received three
      diets for 4 weeks each: SFA-rich diet, Mediterranean (Med) diet enriched in MUFA
      with virgin olive oil, and a low-fat, high-carbohydrate diet enriched in n-3 PUFA
      (alpha-linolenic acid from plant origin) (CHO-PUFA diet). After 12 h of fasting,
      volunteers received a breakfast reflecting the fatty acid composition of the diet
      ingested in the preceding dietary period. Med diet induced higher postprandial
      SOD2 and TrxR mRNA levels, and CHO-PUFA diet induced higher GPx1 and TrxR mRNA
      levels compared with SFA-rich diet. Med and CHO-PUFA breakfasts induced a
      postprandial increase in plasma reduced glutathione (GSH), and a greater
      postprandial GSH/oxidized glutathione ratio compared to the SFA-rich diet. Our
      study suggests that the consumption of Med and CHO-PUFA diets may reduce
      postprandial oxidative stress compared to an SFA-rich diet, which may be due to
      higher antioxidant enzymes gene expression in adipose tissue. 

PMID- 23963802
TI  - Vitamin E delta-tocotrienol prolongs survival in the LSL-KrasG12D/+;LSL
      Trp53R172H/+;Pdx-1-Cre (KPC) transgenic mouse model of pancreatic cancer.
AB  - Previous work has shown that vitamin E delta-tocotrienol (VEDT) prolongs survival
      and delays progression of pancreatic cancer in the LSL-Kras(G12D)(/+);Pdx-1-Cre
      mouse model of pancreatic cancer. However, the effect of VEDT alone or in
      combination with gemcitabine in the more aggressive LSL-Kras(G12D)(/+);LSL
      Trp53(R172H)(/+);Pdx-1-Cre (KPC) mouse model is unknown. Here, we studied the
      effects of VEDT and the combination of VEDT and gemcitabine in the KPC mice. KPC
      mice were randomized into four groups: (i) vehicle [olive oil, 1.0 mL/kg per os
      twice a day and PBS 1.0 mL/kg intrapertoneally (i.p.) twice a week], (ii)
      gemcitabine (100 mg/kg i.p. twice a week), (iii) VEDT (200 mg/kg per os twice a
      day), and (iv) gemcitabine + VEDT. Mice received treatment until they displayed
      symptoms of impending death from pancreatic cancer, at which point animals were
      euthanized. At 16 weeks, survival was 10% in the vehicle group, 30% in the
      gemcitabine group, 70% in the VEDT group (P < 0.01), and 90% in the VEDT combined
      with gemcitabine group (P < 0.05). VEDT alone and combined with gemcitabine
      resulted in reversal of epithelial-to-mesenchymal transition in tumors.
      Biomarkers of apoptosis (plasma CK18), PARP1 cleavage, and Bax expression were
      more greatly induced in tumors subjected to combined treatment versus individual
      treatment. Combined treatment induced cell-cycle inhibitors (p27(Kip1) and
      p21(Cip1)) and inhibited VEGF, vascularity (CD31), and oncogenic signaling (pAKT,
      pMEK, and pERK) greater than individual drugs. No significant differences in body
      weight gain between drug treatment and control mice were observed. These results
      strongly support further investigation of VEDT alone and in combination with
      gemcitabine for pancreatic cancer prevention and treatment.

PMID- 23963803
TI  - beta-Escin inhibits NNK-induced lung adenocarcinoma and ALDH1A1 and RhoA/Rock
      expression in A/J mice and growth of H460 human lung cancer cells.
AB  - Lung cancer is the leading cause of cancer-related deaths. beta-Escin, a
      triterpene saponin isolated from horse chestnut seeds, was tested for inhibition
      of lung adenoma and adenocarcinoma induced by the tobacco carcinogen 4-(methyl
      nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female A/J mice; and its possible
      mode of action was evaluated using the H460 human lung cancer cell line. At 6
      weeks of age, 35 mice were fed AIN-76A-modified diet, and one week later, lung
      tumors were induced with a single intraperitoneal (i.p.) injection of 10 MUmol
      NNK/mouse. Three weeks after the NNK treatment, groups of mice were fed either
      control or experimental diets containing 500 ppm for 20 weeks (10 control, 5 beta
      escin) or 36 weeks (15 control, 5 beta-escin) and evaluated for lung tumor via
      histopathologic methods. Administration of 500 ppm beta-escin significantly
      suppressed lung tumor (adenoma + adenocarcinoma) formation by more than 40% (P <
      0.0015) at 20 weeks and by 53.3% (P < 0.0001) at 37 weeks. beta-Escin inhibited
      NNK-induced lung adenocarcinoma formation by 65% (P < 0.001) at 20 weeks and by
      53% (P < 0.0001) at 37 weeks. Immunohistochemical analysis revealed that lung
      tumors from mice exposed to beta-escin showed significantly reduced aldehyde
      dehydrogenase (ALDH)1A1 and phospho-Akt (p-Akt) expression when compared with
      those in mice fed control diet. Aldefluor assay for ALDH revealed that among H460
      lung cancer cells treated with different concentrations of beta-escin (0-40
      MUmol/L), the subpopulation of cells with elevated ALDH activity was inhibited
      significantly. Our findings suggest that beta-escin inhibits tobacco carcinogen
      induced lung tumor formation by modulating ALDH1A1-positive cells and RhoA/Rock
      signaling.

PMID- 23963804
TI  - Reduced aflatoxin exposure presages decline in liver cancer mortality in an
      endemic region of China.
AB  - Primary liver cancer (PLC) is the third leading cause of cancer mortality
      globally. In endemic areas of sub-Saharan Africa and Asia, PLC largely arises
      from chronic infection with hepatitis B virus (HBV) and ingestion of aflatoxins.
      Although synergistic interactions between these two risk factors have been
      observed in cohort studies in China, here we determined the impact of
      agricultural reforms in the 1980s leading to diminished maize consumption and
      implementation of subsidized universal vaccination against HBV in the 2000s on
      PLC primary prevention. A population-based cancer registry was used to track PLC
      mortality in Qidong, China and was compared with the timeline of HBV
      immunization. Randomly selected serum samples from archived cohort collections
      from the 1980s to present were analyzed for aflatoxin biomarkers. More than 50%
      reductions in PLC mortality rates occurred across birth cohorts from the 1960s to
      the 1980s for Qidongese less than 35 years of age although all were born before
      universal vaccination of newborns. Median levels of the aflatoxin biomarker
      decreased from 19.3 pg/mg albumin in 1989 to undetectable (<0.5 pg/mg) by 2009. A
      population attributable benefit of 65% for reduced PLC mortality was estimated
      from a government-facilitated switch of dietary staple from maize to rice; 83% of
      this benefit was in those infected with HBV. Food policy reforms in China
      resulted in a dramatic decrease in aflatoxin exposure, which, independent of HBV
      vaccination, reduced liver cancer risk. The extensive HBV vaccine coverage now in
      place augurs even greater risk reductions in the future.

PMID- 23963805
TI  - Arterial compression of nerve is the primary cause of trigeminal neuralgia.
AB  - Whether arterial or venous compression or arachnoid adhesions are primarily
      responsible for compression of the trigeminal nerve in patients with trigeminal
      neuralgia is unclear. The aim of this study was to determine the causes of
      trigeminal nerve compression in patients with trigeminal neuralgia. The surgical
      findings in patients with trigeminal neuralgia who were treated by micro vascular
      decompression were compared to those in patients with hemifacial spasm without
      any signs or symptoms of trigeminal neuralgia who were treated with microvascular
      decompression. The study included 99 patients with trigeminal neuralgia (median
      age, 57 years) and 101 patients with hemifacial spasm (median age, 47 years).
      There were significant differences between the groups in the relationship of
      artery to nerve (p < 0.001) and the presence of arachnoid adhesions (p < 0.001)
      but no significant difference in relationship of vein to nerve. After adjustment
      for age, gender, and other factors, patients with vein compression of nerve or
      with artery compression of nerve were more likely to have trigeminal neuralgia
      (OR = 5.21 and 42.54, p = 0.026 and p < 0.001, respectively). Patients with
      arachnoid adhesions were less likely to have trigeminal neuralgia (OR = 0.15, p =
      0.038). Arterial compression of the trigeminal nerve is the primary cause of
      trigeminal neuralgia and therefore, decompression of veins need not be a priority
      when performing microvascular dissection in patients with trigeminal neuralgia.

PMID- 23963806
TI  - Standardization and normative data obtained in the Italian population for a new
      verbal fluency instrument, the phonemic/semantic alternate fluency test.
AB  - The phonemic/semantic alternate fluency test seems to overcome some limits of the
      instruments currently used to assess set-shifting abilities. In particular, this
      test does not make high demands on motor systems because the subject is required
      to rapidly change mental set to generate words by continuously alternating
      between phonemic and semantic criteria. Thus, it is potentially feasible for use
      in individuals who have movement disorders. In this regard, some data support its
      sensitivity in revealing cognitive impairments in people suffering from frontal
      striatal-related disorders. The first aim of this study was to provide
      standardization and normative data for the phonemic/semantic alternate fluency
      test. The second aim was to upgrade normative data for the single phonemic and
      semantic fluency tests. For these purposes, we administered to a sample of 335
      healthy Italian subjects (ranging from 20 to 90 years), a test consisting of the
      following three subtests: (1) a single letter-cued (phonemic) fluency subtest;
      (2) a single category-cued (semantic) subtest; (3) a phonemic/semantic alternate
      fluency subtest. A composite shifting index was also derived to capture the
      shifting cost a subject pays passing from performance of the two single fluency
      subtests to performance of the alternate fluency subtest. We computed correction
      grids to adjust raw scores for age, literacy and gender according to the results
      of regression analyses. Moreover, we computed equivalent scores to permit direct
      and fast comparison of performance on the three fluency tests.

PMID- 23963807
TI  - Intra- and interspecific activities of semiochemicals from the sex pheromone
      gland of the Welsh Clearwing, Synanthedon scoliaeformis.
AB  - Analysis of the sex pheromone gland of virgin Synanthedon scoliaeformis females
      by gas chromatography/mass spectrometry revealed six compounds structurally
      related to sex pheromone components of other clearwing moths: (E,Z)-2,13
      octadecadienyl acetate (E2,Z13-18:OAc), (E,Z)-2,13-octadecadienol, octadecanol
      acetate, octadecanol, (Z,Z)-3,13-octadecadienyl acetate (Z3,Z13-18:OAc), and (Z)
      13-octadecenyl acetate. Trapping tests demonstrated that E2,Z13-18:OAc is the sex
      pheromone of S. scoliaeformis and is essential for attracting males; addition of
      the other compounds did not enhance catch. Synanthedon scoliaeformis and S.
      tipuliformis are the only Palearctic clearwing moths whose distribution range and
      seasonal flight periods overlap and that are known to use E2,Z13-18:OAc in sex
      pheromonal communication. Hourly monitoring of male catches in traps revealed
      that sex pheromone communication in S. scoliaeformis and S. tipuliformis species
      follows different diurnal patterns. Z3,Z13-18:OAc, found in S. scoliaeformis
      females, is a known behavioral antagonist against S. tipuliformis males, while
      (E,Z)-3,13-octadecadienyl acetate, a minor sex pheromone component of S.
      tipuliformis, is an antagonist against S. scoliaeformis males. The effect of sex
      pheromones and antagonists, combined with different diurnal mate searching times,
      contribute to the specificity of sex communication channels in these two
      clearwing moth species. 

PMID- 23963808
TI  - Three-dimensional graphene/metal oxide nanoparticle hybrids for high-performance
      capacitive deionization of saline water.
AB  - A novel and general method is proposed to construct three-dimensional
      graphene/metal oxide nanoparticle hybrids. For the first time, it is demonstrated
      that this graphene-based composite with open pore structures can be used as the
      high-performance capacitive deionization (CDI) electrode materials, which
      outperform currently reported materials. This work will offer a promising way to
      develop highly effective CDI electrode materials. 

PMID- 23963809
TI  - Comparison of different cooling rates for fibroblast and keratinocyte
      cryopreservation.
AB  - Easy, cost-effective and reliable cryopreservation protocols are crucial for the
      successful and effective application of tissue engineering. Several different
      protocols are in use, but no comprehensive comparisons across different machine
      based and manual methods have been made. Here, we compare the effects of
      different cooling rates on the post-thaw survival and proliferative capacity of
      two basic cell lines for skin tissue engineering fibroblasts and keratinocytes,
      cultured and frozen in suspension or as a monolayer. We demonstrate that
      effectiveness of cryopreservation cannot be reliably determined immediately after
      thawing: the results at this stage were not indicative of cell growth in culture
      3 days post-thaw. Cryopreservation of fibroblasts in an adherent state greatly
      diminishes their subsequent growth potential. This was not observed when freezing
      in suspension. In keratinocytes, however, adherent freezing is as effective as
      freezing in suspension, which could lead to significant cost and labour savings
      in a tissue-engineering environment. The 'optimal' cryopreservation protocol
      depends on cell type and intended use. Where time, ease and cost are dominant
      factors, the direct freezing into a nitrogen tank (straight freeze) approach
      remains a viable method. The most effective solution across the board, as
      measured by viability 3 days post-thaw, was the commonly used, freezing container
      method. Where machine-controlled cryopreservation is deemed important for tissue
      engineering Good Manufacturing Practice, we present results using a portfolio of
      different cooling rates, identifying the 'optimal' protocol depending on cell
      type and culture method. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 23963810
TI  - Overexpression of caldesmon is associated with lymph node metastasis and poorer
      prognosis in patients with oral cavity squamous cell carcinoma.
AB  - BACKGROUND: A previous comparative tissue proteomics study by the authors of the
      current study led to the identification of caldesmon (CaD) as one of the proteins
      associated with cervical metastasis of oral cavity squamous cell carcinoma
      (OSCC). In the current investigation, the authors focused on the potential
      functions of CaD in patients with OSCC. METHODS: CaD expression was examined in
      tissue samples from 155 patients using immunohistochemical analysis. The
      expression of CaD variants was determined by Western blot analysis and reverse
      transcriptase-polymerase chain reaction. In addition, the specific effects of CaD
      gene overexpression and silence were determined in OSCC cell lines. RESULTS: CaD
      expression was found to be significantly higher in tumor cells from metastatic
      lymph nodes compared with primary tumor cells, and was nearly absent in normal
      oral epithelia. Higher CaD expression was found to be correlated with positive N
      classification, poor differentiation, perineural invasion, and tumor depth (P =
      .001, P = .029, P = .001, and P = .031, respectively). In survival analyses, OSCC
      patients with higher CaD expression were found to have poorer prognosis with
      regard to disease-specific survival and disease-free survival (P = .003 and P =
      .014, respectively). Multivariate analyses further indicated that higher CaD
      expression was an independent predictor of disease-specific survival (P = .043).
      Serum CaD levels were found to be significantly higher in patients with OSCC, but
      this finding was not associated with clinicopathological manifestations. Data
      obtained from in vitro suppression, rescue, and overexpression of CaD in OEC-M1
      cells indicated that CaD promotes migration and invasive processes in OSCC cells.
      CONCLUSIONS: The findings of the current study collectively suggest that the low
      molecular-weight CaD expression in OSCC tumors is associated with tumor
      metastasis and patient survival.

PMID- 23963812
TI  - Panhypopituitarism in a pregnant women caused by a cystic sellar lesion.

PMID- 23963811
TI  - Maternal nutritional history modulates the hepatic IGF-IGFBP axis in adult male
      rat offspring.
AB  - Alterations in early life nutrition lead to an increased risk of obesity and
      metabolic syndrome in offspring. We have shown that both relative maternal
      undernutrition (UN) and maternal obesity result in metabolic derangements in
      offspring, independent of the postnatal dietary environment. Since insulin-like
      growth factor binding protein 2 (IGFBP2) has been shown to be independently
      associated with obesity and diabetes risk, we examined the IGF-IGFBP axis in male
      rat offspring following either maternal UN or maternal obesity to explain
      possible common pathways in the development of metabolic disorders. Wistar rats
      were time-mated and fed either a control diet (CONT), 50 % of CONT (UN) or a high
      fat (HF) diet throughout pregnancy. Male offspring were weaned onto a standard
      chow diet and blood and tissues were collected at postnatal day 160. Plasma and
      hepatic tissue samples were analysed for key players in the IGF-IGFBP system.
      Both maternal UN and HF resulted in increased fat mass, hyperinsulinemia,
      hyperleptinemia and altered blood lipid profiles in offspring compared to CONT.
      Circulating IGF-1 and IGFBP3 levels and hepatic mRNA expression of IGFBP1 and
      IGFBP2 were significantly decreased in UN and HF offspring compared to CONT. DNA
      methylation of the IGFBP2 promotor region was similar between maternal dietary
      groups. Although chaperone gene heat-shock protein 90 and hepatic IGFBP1 were
      significantly correlated in CONT offspring this effect was absent in both UN and
      HF offspring. In conclusion, this study is one of the first to directly compare
      two experimental models of developmental programming representing both ends of
      the maternal dietary spectrum. Our data suggest that two disparate nutritional
      models that elicit similar adverse metabolic phenotypes in offspring are
      characterised by common alterations in the IGF-IGFBP pathway.

PMID- 23963813
TI  - Energy dependence of HCD on peptide fragmentation: stepped collisional energy
      finds the sweet spot.
AB  - An understanding of the process of peptide fragmentation and what parameters are
      best to obtain the most useful information is important. This is especially true
      for large-scale proteomics where data collection and data analysis are most often
      automated, and manual interpretation of spectra is rare because of the vast
      amounts of data generated. We show herein that collisional cell peptide
      fragmentation, in this case higher collisional dissociation (HCD) in the Q
      Exactive, is significantly affected by the normalized energy applied. Both
      peptide sequence and energy applied determine what ion fragments are observed.
      However, by applying a stepped normalized collisional energy scheme and combining
      ions from low, medium, and high collision energies, we are able to increase the
      diversity of fragmentation ions generated. Application of stepped collision
      energy to HEK293T lysate demonstrated a minimal effect on peptide and protein
      identification in a large-scale proteomics dataset, but improved phospho site
      localization through increased sequence coverage. Stepped HCD is also beneficial
      for tandem mass tagged (TMT) experiments, increasing intensity of TMT reporters
      used for quantitation without adversely effecting peptide identification. 

PMID- 23963814
TI  - Protective role of hydrogen peroxide pretreatment on defense systems and BnMP1
      gene expression in Cr(VI)-stressed canola seedlings.
AB  - To evaluate the ameliorating effects of hydrogen peroxide (H2O2, 200 MUM) on
      hexavalent chromium [Cr(VI)] toxicity in canola (Brassica napus L.), we focused
      on the plant growth, chlorophyll content, thiol contents, lipid peroxidation,
      antioxidant enzymes, and the expression of metallothionein protein (BnMP1) mRNA.
      Cr(VI) at 50 MUM significantly decreased the plant growth (fresh and dry
      weights). The decrease in growth was accompanied by increased lipid peroxidation
      and decreased chlorophyll content in leaves. Hydrogen peroxide pretreatment,
      however, enhanced plant growth parameters and led to the reduced levels of lipid
      peroxidation and higher levels of pigment. In addition, H2O2 pretreatment
      increased Cr accumulation in aerial parts of seedlings. The tendency of increase
      in thiol content under Cr(VI) stress was further increased with H2O2
      pretreatment. The activities of antioxidant enzymes such as superoxide dismutase
      (SOD), ascorbate peroxidase (APX), guaiacol peroxidase (POD) and catalase (CAT)
      were differentially altered. SOD and POD activities increased under Cr(VI)
      stress, whereas APX and CAT activities decreased. The SOD and CAT activities
      remained unaffected in both durations due to H2O2 pretreatment, but activities of
      APX and POD were promoted in the Cr(VI)-stressed seedlings. Metallothioneins are
      a family of low-molecular-weight Cys-rich proteins and are thought to play a
      possible role in metal metabolism or detoxification. In real-time quantitative
      PCR analysis, the expression level of BnMP1 mRNA was increased at 1 day after
      treatment (DAT), whereas it was decreased at 7 DAT in Cr(VI)-stressed seedlings.
      At 1 DAT, pretreatment of H2O2 before Cr(VI) stress reduced the expression of
      BnMP1 mRNA as compared to Cr(VI) stress alone, but this effect was not
      significant. At 7 DAT, H2O2 pretreatment alleviated the Cr(VI) stress-mediated
      decrease in the expression of BnMP1 mRNA. These results suggest that H2O2 may act
      as a signal that triggers defense mechanisms which in turn protects canola
      seedlings from Cr(VI)-induced oxidative damage.

PMID- 23963815
TI  - The sixteenth iron in the nitrogenase MoFe protein.
AB  - Another iron in the fire: X-ray anomalous diffraction studies on the nitrogenase
      MoFe protein show the presence of a mononuclear iron site, designated as Fe16,
      which was previously identified as either Ca(2+) or Mg(2+). The position of the
      absorption edge indicates that this site is in the oxidation state +2. The high
      sequence conservation of the residues coordinated to Fe16 emphasizes the
      potential importance of the site in nitrogenase.

PMID- 23963816
TI  - Correlates of physical activity in adults with rheumatoid arthritis: a systematic
      review.
AB  - BACKGROUND: Physical activity (PA) is an important component in the management of
      Rheumatoid Arthritis (RA). To date the correlates of PA have not been thoroughly
      investigated in the RA population. The aim of this systematic review was to
      determine the correlates of PA in the adult RA population. METHODS: A search of
      Medline, EMBASE, AMED, CINAHL plus, Pubmed, Web of Science, and the Cochrane
      Library was conducted. A manual search of reference lists was conducted to
      compliment the electronic search. Ten studies fulfilled the inclusion criteria
      and were assessed for methodological quality. RESULTS: Results determined
      correlates in 4 categories: sociodemographic, physical, psychological and social
      variables. The variables varied greatly and were inconsistently studied. Changes
      were noted from a previous review in 2005 in relation to the association between
      certain variables and PA, including age, gender, disease duration, pain, exercise
      beliefs and social support. CONCLUSIONS: Positive associations with PA were found
      for motivation, self-efficacy, health perception, and previous PA levels.
      Negative associations were found for fatigue, a coerced regulation style and
      certain physiological variables. In addition differences between correlates of PA
      in the adult RA population and other chronic disease and healthy adult
      populations have been demonstrated.

PMID- 23963817
TI  - The role of community health centers in providing behavioral health care.
AB  - The prevalence of behavioral health problems is higher for low-income
      individuals, yet this population is less likely to receive behavioral health
      treatment. Community health centers have their advantages as behavioral health
      care providers because they serve a majority low-income population and are
      located in medically underserved areas. Their role in providing behavioral health
      care is expected to expand under health reform as they are expected to double
      their patient capacity, and due to increased insurance coverage for individuals
      with behavioral health problems. However, the ability of community health centers
      to provide behavioral health care is compromised by provider shortages and
      funding shortfalls. 

PMID- 23963818
TI  - Automatically purification of aqueous CdTe nanocrystals in water-ethanol co
      environment.
AB  - Purification is a separated post-treatment step after the synthesis of
      nanocrystals (NCs) in order to exclude excess ligands and monomers in NC
      solution. The common purification process involves many manipulations, such as
      concentrating, addition of anti-solvents and centrifugation, which are
      troublesome and time consuming. In this work, we originally integrate NC
      synthesis and NC purification in one-pot via selecting water-ethanol co
      environment for NC synthesis and NC purification. Our research shows that NCs can
      grow in water-ethanol mixture. When growing into critical size, NCs will
      automatically precipitate from the solution. Element analysis demonstrates that
      precipitates fraction fits well with stoichiometric of ligand-capped NCs. Excess
      monomers are left in supernatant, and thus achieving automatically purification
      of NCs in the water-ethanol co-environment. By adjusting the volume ratios of
      water and ethanol in bi-solvent system, different-sized purified NCs can be
      controlled. Besides, this water-ethanol co-environment can be used in both
      thermal-promoted and hydrazine-promoted growth. 

PMID- 23963819
TI  - A cross-cultural segmentation of western Balkan consumers: focus on preferences
      toward traditional fresh cow cheese.
AB  - BACKGROUND: Western Balkan countries (WBCs) have a long-standing culinary
      tradition. The promotion of traditional foods may be a tool for coping with
      modernisation trends in such transition economies. This paper explores consumer
      preferences toward food in this region, focusing on a traditional fresh cow
      cheese locally called 'Mladi Sir'. This product was quoted in all the preliminary
      focus groups as a common traditional product present in the six WBCs studied:
      Bosnia-Herzegovina, Croatia, Macedonia, Montenegro, Serbia and Slovenia. RESULTS:
      After a literature review investigating the concept of traditional food in WBCs
      and the implementation of focus groups, a survey including a conjoint analysis on
      preferences for fresh cow cheese was carried out in 2011 to collect data from
      1200 respondents. Four clusters of consumers were identified: one focused more on
      the local origin; one oriented more toward the scale of production (on-farm and
      small dairy); the third favouring low prices and the fourth preferring high
      prices and industrial products. CONCLUSION: Policy makers and the supply chain
      could take these differences in consumer preferences regarding traditional food
      products into account in order to develop specific strategies.

PMID- 23963820
TI  - Conformational stability of CopC and roles of residues Tyr79 and Trp83.
AB  - CopC is a periplasmic copper Chaperone protein that has a beta-barrel fold and
      two metal-binding sites distinct for Cu(II) and Cu(I). In the article, four
      mutants (Y79F, Y79W, Y79WW83L, Y79WW83F) were obtained by site-directed
      mutagenesis. The far-UV CD spectra of the proteins were similar, suggesting that
      mutations did not bring any significant changes in secondary structures.
      Meanwhile the effects of mutations on the protein's function were manifested by
      Cu(II) binding. Fluorescence lifetime measurement and quenching of tryptophan
      fluorescence by acrylamide and KI showed that the microenvironment around Trp83
      was more hydrophobic than that around Tyr79 in apoCopC. Unfolding experiments
      induced by guanidinium chloride (GdnHCl), urea provided the conformational
      stability of each protein. The Delta<DeltaG(0) element > obtained using the model
      of structural elements was used to show the role of Tyr79 and Trp83. On the one
      hand, the <DeltaG(0) element > induced by urea for Y79F, Y79W have a loss of
      6.51, 2.03 kJ/mol, respectively, compared with apoCopC, proving that replacement
      of Tyr79 by Phe or Trp all decreased the protein stability, meaning that the
      hydrogen bonds interactions between Tyr79 and Thr75 played an important role in
      stabilizing apoCopC. On the other hand, the <DeltaG(0) element > induced by urea
      for Y79WW83L have a loss of 11.44 kJ/mol, but for Y79WW83F did a raise of 1.82
      kJ/mol compared with Y79W. The replacement of Trp83 by Phe and Leu yields
      opposite effects on protein stability, which suggested that the aromatic ring of
      Trp83 was important in maintaining the hydrophobic core of apoCopC. 

PMID- 23963821
TI  - Bone mineral density following surgical oophorectomy and tamoxifen adjuvant
      therapy for breast cancer.
AB  - BACKGROUND: In premenopausal women treated for breast cancer, loss of bone
      mineral density (BMD) follows from menopause induced by chemotherapy or loss of
      ovarian function biochemically or by surgical oophorectomy. The impact on BMD of
      surgical oophorectomy plus tamoxifen therapy has not been described. METHODS: In
      270 Filipino and Vietnamese premenopausal patients participating in a clinical
      trial assessing the impact of the timing in the menstrual cycle of adjuvant
      surgical oophorectomy on breast cancer outcomes, BMD was measured at the lumbar
      spine and femoral neck before this treatment, and at 6, 12, and 24 months after
      surgical and tamoxifen therapies. RESULTS: In women with a pretreatment BMD
      assessment and at least 1 other subsequent BMD assessment, no significant change
      in femoral neck BMD was observed over the 2-year period (-0.006 g/cm2 , -0.8%, P
      = .19), whereas in the lumbar spine, BMD fell by 0.045 g/cm2 (4.7%) in the first
      12 months (P < .0001) and then began to stabilize. CONCLUSIONS: Surgically
      induced menopause with tamoxifen treatment is associated with loss of BMD at a
      rate that lessens over 2 years in the lumbar spine and no significant change of
      BMD in the femoral neck.

PMID- 23963824
TI  - N-doped graphene natively grown on hierarchical ordered porous carbon for
      enhanced oxygen reduction.
AB  - A novel nitrogen doped hybrid material composed of in situ-formed graphene
      natively grown on hierarchical ordered porous carbon is prepared, which
      successfully combines the advantages of both materials, such as high surface
      area, high mass transfer, and high conductivity. The outstanding structural
      properties of the resultant material render it an excellent metal-free catalyst
      for electrochemical oxygen reduction. 

PMID- 23963822
TI  - Neural correlates of inefficient filtering of emotionally neutral distractors
      from working memory in trait anxiety.
AB  - Research has indicated that highly trait-anxious (HTA) individuals exhibit a
      specific deficit in filtering threat-related distractors from visual-spatial
      working memory (WM). Prior demonstrations of impaired inhibition control in HTA
      individuals have mainly focused on tasks that required the inhibition of
      prepotent response tendencies. Studies on the suppression of emotionally neutral
      distractors from WM in trait anxiety have also been minimal. In this article, we
      present a study on the manifestation of general inefficient filtering of neutral
      distractors during visual-spatial WM maintenance stages in HTA individuals.
      Female participants performed a visual-spatial WM task while event-related
      potentials were recorded. They were made to remember the orientations of red
      rectangles within half of the screen and to ignore all salient green rectangles.
      As predicted, no significant main effect of group and no interaction between
      group and condition were found in the N2pc component, suggesting that group
      differences did not manifest in the initial process of object individuation.
      During the subsequent WM maintenance phase, HTA individuals were highly
      inefficient at filtering the irrelevant items from WM, as reflected not only by
      parallel late contralateral delay activity (CDA; 450 to 900 ms) amplitudes for
      the distractor condition and the four red items, but also by a smaller filtering
      efficiency score in the HTA group than in the low-trait-anxiety group. Extending
      previous studies, our findings verify a general filtering impairment in HTA
      individuals for task-irrelevant salient distractors during a WM maintenance
      phase. 

PMID- 23963825
TI  - Downregulation of miR-15a due to LMP1 promotes cell proliferation and predicts
      poor prognosis in nasal NK/T-cell lymphoma.
AB  - Nasal NK/T-cell lymphoma (NNKTL) is an Epstein-Barr virus (EBV)-associated
      malignancy and has distinct clinical and histological features. However, its
      genetic features are hitherto unclear. MicroRNAs (miRNAs) play a crucial role in
      the pathogenesis of several malignancies via regulating gene expression. In this
      study, we investigated whether the specific microRNAs were related to the tumor
      behaviors in NNKTL. MiRNA array and Quantitative RT-PCR analyses revealed that
      miR-15a was expressed at a much lower level in NNKTL cells (SNK-1, SNK-6, and SNT
      8) than in normal peripheral NK cells and EBV-negative NK cell line KHYG-1.
      Quantitative PCR and western blot analyses showed that the expression of MYB and
      cyclin D1, which are validated targets of miR-15a, was higher in NNKTL cells.
      Transfection of NNKTL cells (SNK-6 and SNT-8) with a miR-15a precursor decreased
      MYB and cyclin D1 levels, thereby blocking G1/S transition and cell
      proliferation. Knockdown of EBV-encoded latent membrane protein 1 (LMP1)
      significantly increased miR-15a expression in SNK-6 cells. In NNKTL tissues, we
      found that reduced miR-15a expression, which correlated with MYB and cyclin D1
      expression, was associated with poor prognosis of NNKTL patients. These data
      suggest that downregulation of miR-15a, possibly due to LMP1, implicates in the
      pathogenesis of NNKTL by inducing cell proliferation via MYB and cyclin D1. Thus,
      miR-15a could be a potential target for antitumor therapy and a prognostic
      predictor for NNKTL.

PMID- 23963826
TI  - A lower serum level of middle-molecular-weight adiponectin is a risk factor for
      endometrial cancer.
AB  - BACKGROUND: The present study was undertaken to examine the correlation between
      serum levels of adiponectin isoforms and the risk for endometrial cancer.
      METHODS: This retrospective case-control study included 43 Japanese women with
      endometrial cancer and 62 Japanese women with no history of cancer. Serum levels
      of total adiponectin and the respective isoforms were determined by enzyme-linked
      immunosorbent assay. Multivariate logistic regression analysis was performed on
      the serum levels of total adiponectin and its isoforms, high molecular weight,
      middle molecular weight, and low molecular weight adiponectins, after adjustment
      for confounders (age, body mass index, hypertension, and diabetes mellitus).
      RESULTS: The distribution of body mass index revealed a statistically significant
      difference between patients and controls (P = 0.001). A statistically significant
      difference (P < 0.01) was also found in the incidence of diabetes mellitus
      between the two groups, although there was no significant difference in the
      incidence of hypertension. In controls, an inverse correlation was observed
      between body mass index and serum adiponectin levels. However, in patients, an
      inverse correlation was found only between body mass index and serum middle
      molecular weight adiponectin level. After adjustment for confounding variables,
      the factor found to be most closely associated with endometrial cancer was a
      lower serum level of middle molecular weight adiponectin (adjusted odds ratio
      4.89, 95 % confidence interval value 1.25-19.11, P = 0.022). CONCLUSION: Low
      serum level of middle molecular weight adiponectin was the only independent risk
      factor for endometrial cancer suggesting that the application of adiponectin
      might prevent or decrease the risk for endometrial cancer.

PMID- 23963827
TI  - Palladium(II)-catalyzed direct conversion of methyl arenes into aromatic
      nitriles.
AB  - From methyl to nitrile: A mild ammoxidation method, which directly converts
      methyl arenes into aromatic nitriles, has been developed by using Pd(OAc)2 and N
      hydroxyphthalimide (NHPI) as the catalysts, and tert-butyl nitrite as the
      nitrogen source and oxidant.

PMID- 23963828
TI  - 'Is it worth it?' A qualitative study of the beliefs of overweight and obese
      physically active children.
AB  - BACKGROUND: The specific circumstances and contexts that may affect overweight
      and obese children's participation in physical activity have thus far been given
      little attention. The qualitative study discussed in this paper explores the
      experiences of overweight and obese children and young people who have
      successfully increased their activity levels. METHODS: The study sample was
      recruited from a community health and fitness scheme for children aged 5 to 16,
      with a Body Mass Index (BMI) at or above the 91st centile. Semistructured
      interviews were conducted with 58 children and young people. Data were analyzed
      using template analysis. RESULTS: The children increased their feelings of
      capability to undertake physical activity, both while on the scheme and in other
      physical activity settings. They valued the range of 'noncompetitive' activities
      available and the nonthreatening atmosphere created. The 'emotional' support
      offered by the instructors was perceived as being integral to their enjoyment and
      continued participation. CONCLUSIONS: Physical activity providers need to be able
      to generate opportunities which allow children of any weight status to
      participate without fear of stigmatization or bullying. The findings of the
      current study suggest that to be effective what we should be focusing on is
      improving the physical activity experience from the child's perspective.

PMID- 23963829
TI  - Clinical significance of circulating tumor cells in peripheral blood from
      patients with gastric cancer.
AB  - BACKGROUND: The authors hypothesized that circulating tumor cells (CTCs) in
      patients with gastric cancer are associated with prognosis and disease
      recurrence. In this study, they evaluated CTCs in gastric cancer and clarified
      the clinical impact of CTCs. METHODS: In total, 265 consecutive patients with
      gastric cancer were enrolled. Fourteen patients were excluded from the analysis,
      including 12 patients who another cancer and 2 patients who refused the
      treatment. The remaining 251 patients were divided into 2 groups: 148 patients
      who underwent gastrectomy (the resection group) and 103 patients who did not
      undergo gastrectomy (the nonresectable group). Peripheral blood samples were
      collected before gastrectomy or chemotherapy. A proprietary test for capturing,
      identifying, and counting CTCs in blood was used for the isolation and
      enumeration of CTCs. RESULTS: CTCs were detected in 16 patients (10.8%) from the
      resection group and in 62 patients (60.2%) from the nonresectable group. The
      overall survival rate for the entire cohort was significantly lower in patients
      with CTCs than in those without CTCs (P < .0001). In the resection group, relapse
      free and overall survival in patients with CTCs was significantly lower than in
      patients without CTCs (P < .0001). It was noteworthy that the expression of CTCs
      was an independent factor for determining the overall survival of patients with
      gastric cancer in multivariate analysis (P = .024). In the nonresectable group,
      the overall survival rate was significantly lower in patients with CTCs than in
      those without CTCs (P = .0044). CONCLUSIONS: The evaluation of CTCs in peripheral
      blood may be a useful tool for predicting tumor progression, prognosis, and the
      effect of chemotherapy in patients with gastric cancer.

PMID- 23963830
TI  - Establishment of a methodology for identifying Paeoniae Radix based on metallomic
      analysis.
AB  - We aimed to establish a methodology for identifying Paeonia samples based on
      metallomic analysis. We prepared 66 batches of samples (16 batches of crude drugs
      and 50 batches of cultivars, comprising 64 batches of Paeonia lactiflora and 2
      batches of P. veitchii) collected from Japan and China (Inner Mongolia and
      elsewhere) between 1996 and 2008. P. lactiflora samples were genetically
      classified into white peony root (WPR) type and red peony root (RPR) type. Up to
      47 elements were measured by inductively coupled plasma-mass spectrometry, and
      RPR type crude drug samples contained up to five times as much calcium as the
      others. Principal component analysis (PCA) of the multi-element fingerprints
      obtained suggested that P. veitchii, which grows wild, were distinguishable from
      the other cultivated P. lactiflora samples. This was confirmed perfectly by soft
      independent modeling of class analogy (SIMCA). The PCA of the fingerprints of P.
      lactiflora crude drug samples also suggested that it was possible to classify
      them by production area (Japan, Inner Mongolia, and China excluding Inner
      Mongolia) and genetic type (RPR and WPR types). They were also classified 100 %
      to the predicted class by SIMCA in both cases. These analyses were successful
      among the samples whose collection dates varied. This simple metallomic method is
      an efficient approach for verifying the complex origin of Paeoniae Radix.

PMID- 23963831
TI  - Agricultural biodiversity as a link between traditional food systems and
      contemporary development, social integrity and ecological health.
AB  - Traditional food systems offer a key link between the social and economic
      resilience of smallholder farmers and pastoralists and the sustainable food and
      nutrition security of global populations. This paper addresses issues related to
      socio-cultural diversity and the continuing complex engagement of traditional and
      modern communities with the plants and animals that sustain them. In light of
      some of the unhealthful consequences of the 'nutrition transition' to globalized
      modern diets, the authors define and propose a process for a more successful food
      system transition that balances agro-biodiversity and processed commodities to
      support diet diversity, health and social equity alongside sustainable economic
      growth. We review empirical research in support of practice and policy changes in
      agriculture, economic development and health domains as well as cross-sectoral
      and community-based innovation. High-value food crops within domestic and global
      value chains can be an entry point for smallholders' participation as
      contributors and beneficiaries of development, while sustainable small farms, as
      purveyors of environmental and public health services, diversify global options
      for long-term adaptation in the face of environmental uncertainty.

PMID- 23963832
TI  - Different CXCR4 expression according to various histologic subtype of papillary
      thyroid carcinoma.
AB  - Functional chemokine (C-X-C motif) receptor 4 (CXCR4) is well known to be over
      expressed in papillary thyroid carcinoma (PTC). The aim of this study was to
      evaluate whether or not the expression of CXCR4 is different by histological
      subtypes of PTC and to elucidate the relationship between the expression of CXCR4
      and clinicopathologic factors. CXCR4 expression in 127 PTC samples was assessed
      using immunohistochemical staining. The expression of CXCR4 showed different
      patterns according to the histological subtype of PTC (p < 0.001). A strong
      expression of CXCR4 was observed more frequently in the poorly differentiated
      region of PTC (81.0 %) than in classical PTC (50.0 %). Strong CXCR4 expression
      was less frequently shown in follicular variant (33.9 %) and in diffuse
      sclerosing variant (14.3 %) of PTC. CXCR4 expression showed a distinct pattern
      according to the histological subtype of PTC although not associated with other
      clinicopathological parameters. 

PMID- 23963833
TI  - Linear and angular measurements of the foot of modern humans: a test of Morton's
      foot types.
AB  - In his classic research, Morton established two functionally different
      configurations of the bipedal and non-bipedal primate foot: one optimized for
      stability, with a stiff longitudinal arch and adducted first metatarsal, and the
      other for compliance. Modern human feet were seen as conforming to the bipedal
      norm and variation from it as pathology, even though clinical evidence has been
      clear that variation from the norm of a stiff longitudinal arch or adducted first
      metatarsal exists. This study aims to document the variation in linear and
      angular measurements of the foot, using weight-bearing radiographs of 50 randomly
      selected people (25 men) from an urban US Level 1 trauma center. The radiographs
      were obtained to "rule-out" a foot fracture after trauma or as comparison films
      for a contralateral foot injury. Measurements were made using Osirix and
      correlations among the angular and length measurements were determined using
      Stata with P < 0.05 and Bonferroni correction for multiple comparisons. We found
      that foot length was not correlated with angular measurements, except for the
      angle between the first and fifth metatarsal. People with lower medial
      longitudinal arches also had more abducted first metatarsals and more vertical
      posterior facets, in accordance with Morton's foot types. Whether or not this
      variation in modern humans is linked to functionally important consequences
      remains to be determined in future research. With the new evidence of a more
      variable foot structure in fossil hominins, understanding the relationship
      between foot morphology and function becomes more urgent.

PMID- 23963834
TI  - Awareness of genetic counseling and perceptions of its purpose: a survey of the
      Canadian public.
AB  - Genetic counseling can result in better outcomes when clients understand what to
      expect, and at least theoretically, at some point in their lifespan, anyone could
      be referred for or benefit from genetic counseling. Thus, in order to identify
      (and ultimately address) issues around awareness of genetic counseling and
      perceptions of its purpose, we surveyed the Canadian general population. We
      acquired 1,000 telephone numbers corresponding to a demographically
      representative sample of Canada from Survey Sampling International, and invited
      individuals to participate in a telephone-based survey. We administered a purpose
      designed survey (in either French or English) comprising questions regarding:
      demographics, whether or not the individual had heard of genetic counseling, and
      15 Likert scale-rated (strongly disagree-strongly agree) items about the possible
      purposes of genetic counseling. Responses to these 15 items were used to generate
      a total "knowledge score". Of the 1,000 numbers, n = 372 could not be reached,
      and the survey was successfully administered to n = 188 individuals (response
      rate 30 %). Most respondents (n = 129, 69 %) had not heard of genetic counseling,
      and substantial proportions thought that genetic counseling aims to prevent
      genetic diseases and abnormalities, help couples have children with desirable
      characteristics, and help people to understand their ancestry. These data could
      be used to inform the strategy for development of future awareness efforts, and
      as a baseline from which to measure their effects. 

PMID- 23963835
TI  - Intrinsic Au decoration of growing TiO2 nanotubes and formation of a high
      efficiency photocatalyst for H2 production.
AB  - Electrochemical anodization of low-concentration (0.02-0.2 at% Au) TiAu alloys in
      a fluoride electrolyte leads to self-organized TiO2 nanotubes that show a
      controllable, regular in situ decoration with elemental Au nanoclusters of ~5 nm
      in diameter. The degree of self-decoration can be adjusted by the Au
      concentration in the alloy and the anodization time. Such Au particle decorated
      tubes show a high activity for photocatalytic H2 production from ethanol
      solutions. 

PMID- 23963836
TI  - Vasculopathy, inflammation, and blood flow in leg ulcers of patients with sickle
      cell anemia.
AB  - Chronic leg ulcers are frequent and debilitating complications of sickle cell
      anemia. Inadequate blood supply has been postulated to be an important factor in
      their occurrence and delayed healing. Little is known about their
      microcirculatory and histopathological changes. We evaluated the microcirculation
      of lower extremity ulcers with laser speckle contrast imaging and infrared
      thermography and obtained clinical and laboratory characteristics in 18 adults
      with sickle cell anemia and chronic leg ulcers. Skin biopsies were obtained in
      four subjects. Subjects had markers of severe disease, anemia, high degree of
      hemolysis, inflammation, and thrombophilia. The highest blood flow was present in
      the ulcer bed, progressively less in the immediate periwound area, and an
      unaffected control skin area in the same extremity. Microscopic examination
      showed evidence of venostasis, inflammation, and vasculopathy. Blood vessels were
      increased in number, had activated endothelium and evidence of
      thrombosis/recanalization. High blood flow may be due to chronic inflammation,
      cutaneous vasodilatation, venostasis, and in situ thrombosis. These changes in
      skin microcirculation are similar to chronic venous ulcers in the non-sickle cell
      disease (SCD) population, thus suggesting that leg ulcers may be another end
      organ complication with endothelial dysfunction that appears in patients with SCD
      at a younger age and with higher frequency than in the general population.

PMID- 23963837
TI  - Role of capsule endoscopy Pillcam COLON 2 in patients with known or suspected
      Crohn's disease who refused colonoscopy or underwent incomplete colonoscopic
      exam: a case series.
AB  - BACKGROUND: Almost 70-80 % of patients with Crohn's disease and virtually all
      patients with ulcerative colitis have colorectal mucosa involvement. Colon
      capsule endoscopy is an interesting option for patients unable or unwilling to
      undergo colonoscopy. We report our experience with the second-generation colon
      capsule PillCam((r)) COLON 2 in the detection of significant lesions in patients
      with known or suspected Crohn's disease, who refused colonoscopy or underwent
      incomplete colonoscopic exam. METHODS: We have retrospectively reviewed the
      results of capsule endoscopy in 6 patients who refused colonoscopy (n = 3) or
      underwent incomplete colonoscopic exam (n = 3) between March 2011 and October
      2012. In all patients, a CT scan was obtained before capsule endoscopy to rule
      out significant stenosis. RESULTS: In our series of 6 patients, 4 had both small
      bowel and colonic involvement. The use of the PillCam((r)) COLON 2 capsule
      allowed a thorough examination and evaluation of the mucosal lesions with high
      acceptability, the method being perceived as noninvasive by the patients. No
      adverse events related to the capsule or bowel preparation were recorded.
      CONCLUSION: In this patient population, PillCam((r)) COLON 2 capsule endoscopy
      was safe. The capsule findings had an important impact on treatment decisions and
      patient management.

PMID- 23963838
TI  - Intestinal pseudo-obstruction due to small bowel alpha-actin deficiency in a
      child with Ehlers-Danlos syndrome.

PMID- 23963839
TI  - Efficacy of sacral nerve stimulation for poor functional results of J-pouch
      ileoanal anastomosis.
AB  - PURPOSE: Ileoanal anastomoses (J-pouches) are an alternative to permanent ostomy.
      The functional outcomes associated with the use of J-pouches are usually good,
      but continence disorders persist in a significant number of cases and have a
      negative impact on quality of life. The aim of this study was to assess the
      efficacy of sacral nerve stimulation (SNS) for poor functional results after J
      pouch ileoanal anastomosis. METHODS: Patients suffering from severe fecal
      incontinence (FI) following coloproctectomy underwent a staged implant SNS
      procedure. Demographic data and functional results for FI episodes, urgencies per
      week, frequency of stools, ability to defer defecation, and Wexner scores were
      obtained at specified intervals. Patients also completed quality-of-life
      assessments. RESULTS: Four female patients were included in this analysis. All 4
      experienced active and passive FI at baseline and subsequently underwent test
      stimulation with a 75 % success rate. Three received definitive implants. These 3
      patients experienced improvement in functional outcomes at 1, 3, and 6 month
      assessments. Improvements in quality of life were also noted. CONCLUSIONS: Our
      preliminary study suggests that SNS is effective for the treatment of poor
      functional results following J-pouch ileoanal anastomosis; however, larger
      studies with long-term follow-up are needed for confirmation of our findings.

PMID- 23963840
TI  - Antioxidant effects of phosphodiesterase-5 inhibitors: reply.

PMID- 23963841
TI  - Hsp90 prevents interaction between CHIP and HERG proteins to facilitate
      maturation of wild-type and mutant HERG proteins.
AB  - AIMS: We examined the role of Hsp90 in expression and maturation of wild-type
      (WT) and mutant ether-a-go-go related gene (HERG) proteins by using Hsp90
      inhibitors, geldanamycin (GA) and radicicol, and Hsp90 overexpression. METHODS
      AND RESULTS: The proteins were expressed in HEK293 cells or collected from HL-1
      mouse cardiomyocytes, and analysed by western blotting, immunoprecipitation,
      immunofluorescence, and whole-cell patch-clamp techniques. GA and radicicol
      suppressed maturation of HERG-FLAG proteins and increased their immature forms.
      Co-expression of Hsp90 counteracted the effects of Hsp90 inhibitors and
      suppressed ubiquitination of HERG proteins. Overexpressed Hsp90 also inhibited
      the binding of endogenous C-terminus of Hsp70-interacting protein (CHIP) to HERG
      FLAG proteins. Hsp90-induced increase of functional HERG proteins was verified by
      their increased expression on the cell surface and enhanced HERG channel
      currents. CHIP overexpression decreased both mature and immature forms of HERG
      FLAG proteins in cells treated with GA. Hsp90 facilitated maturation of
      endogenous ERG proteins, whereas CHIP decreased both forms of ERG proteins in HL
      1 cells. Mutant HERG proteins harbouring disease-causing missense mutations were
      mainly in the immature form and had a higher binding capacity to CHIP than the
      WT; Hsp90 overexpression suppressed this association. Overexpressed Hsp90
      increased the mature form of HERG(1122fs/147) proteins, reduced its ubiquitinated
      form, increased its immunoreactivity in the endoplasmic reticulum and on the
      plasma membrane, and increased the mutant-mediated membrane current. CHIP
      overexpression decreased the immature form of HERG(1122fs/147) proteins.
      CONCLUSION: Enhancement of HERG protein expression through Hsp90 inhibition of
      CHIP binding might be a novel therapeutic strategy for long QT syndrome 2 caused
      by trafficking abnormalities of HERG proteins.

PMID- 23963842
TI  - NO-dependent CaMKII activation during beta-adrenergic stimulation of cardiac
      muscle.
AB  - AIMS: During beta-adrenergic receptor (beta-AR) stimulation, phosphorylation of
      cardiomyocyte ryanodine receptors by protein kinases may contribute to an
      increased diastolic Ca(2+) spark frequency. Regardless of prompt activation of
      protein kinase A during beta-AR stimulation, this appears to rely more on
      activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), by a not
      yet identified signalling pathway. The goal of the present study was to identify
      and characterize the mechanisms which lead to CaMKII activation and elevated
      Ca(2+) spark frequencies during beta-AR stimulation in single cardiomyocytes in
      diastolic conditions. METHODS AND RESULTS: Confocal imaging revealed that beta-AR
      stimulation increases endogenous NO production in cardiomyocytes, resulting in NO
      dependent activation of CaMKII and a subsequent increase in diastolic Ca(2+)
      spark frequency. These changes of spark frequency could be mimicked by exposure
      to the NO donor GSNO and were sensitive to the CaMKII inhibitors KN-93 and AIP.
      In vitro, CaMKII became nitrosated and its activity remained increased
      independent of Ca(2+) in the presence of GSNO, as assessed with biochemical
      assays. CONCLUSIONS: beta-AR stimulation of cardiomyocytes may activate CaMKII by
      a novel direct pathway involving NO, without requiring Ca(2+) transients. This
      crosstalk between two established signalling pathways may contribute to
      arrhythmogenic diastolic Ca(2+) release and Ca(2+) waves during adrenergic
      stress, particularly in combination with cardiac diseases. In addition, NO
      dependent activation of CaMKII is likely to have repercussions in many cellular
      signalling systems and cell types.

PMID- 23963843
TI  - Use of high-normal levels of haemoglobin A(1C) and fasting plasma glucose for
      diabetes screening and for prediction: a meta-analysis.
AB  - BACKGROUND: Using high-normal levels of haemoglobin A1C (Abnormal-A1C ) or
      fasting plasma glucose (FPG) (Abnormal-FPG) for diabetes screening are expected
      to improve the ability to detect persons with or at high risk of diabetes. We
      assessed the diagnostic and predictive capacity for diabetes of Abnormal-A1C and
      Abnormal-FPG. We compared these to the combined use of the two measures to the
      single use of either measurement. METHODS: We analysed 31 eligible cross
      sectional or cohort studies that assessed diagnostic or predictive ability,
      respectively, by using lower A1C and FPG cutoff values than recommended by
      current diabetes criteria. Positive and negative likelihood ratios (LR+ and LR-)
      were calculated to assess the ability to confirm or exclude diabetes,
      respectively, on the basis of a bivariate random-effects model. RESULTS: With
      both Abnormal-A1C and Abnormal-FPG, the pooled LR+ was above 4 for diagnosing
      diabetes and above 3 for predicting diabetes. However, the pooled LR- for
      predicting diabetes was higher with Abnormal-A1C (0.48) and Abnormal-FPG (0.49)
      in comparison with that for diagnosing diabetes (0.27, Abnormal-A1C ; 0.28,
      Abnormal-FPG). In eight studies that assessed the predictive ability of the
      combination of A1C and FPG, using either Abnormal-A1C or Abnormal-FPG could lower
      LR- to 0.17 from 0.43 for only Abnormal-A1C and from 0.38 for only Abnormal-FPG.
      Accordingly, LR+ was also lowered to 2.37 from 3.36 for only Abnormal-A1C and
      from 3.84 for only-Abnormal-FPG. CONCLUSION: The use of the two blood glucose
      tests had insufficient capacity to identify subjects at high risk for diabetes
      but had considerable capacity to identify undiagnosed diabetes.

PMID- 23963845
TI  - Multidisciplinary approaches to intrahepatic cholangiocarcinoma.
AB  - After hepatocellular carcinoma, intrahepatic cholangiocarcinoma (ICC) is the
      second most common primary hepatic malignancy. The etiology of ICC in most
      patients is not known, but its incidence is on the rise worldwide. There are 3
      morphologic subtypes of ICC that can be characterized on cross-sectional imaging,
      mass forming, periductal infiltrating, and intraductal growth; and the
      radiographic characteristics of ICC may vary based on the subtype. Complete
      surgical resection remains the only potentially curative option for patients with
      ICC. Routine lymphadenectomy at the time of surgical resection should be strongly
      considered, because lymph node status provides important prognostic information.
      After surgery, the 5-year survival rate for ICC remains poor at only 25% to 35%
      in most series. Although numerous clinical trials have been conducted using a
      variety of chemotherapy regimens to treat ICC, systemic options for ICC remain
      limited. Doublet gemcitabine and cisplatin therapy is currently considered the
      standard-of-care first-line therapy for patients with advanced disease. Because
      ICC is typically confined to the liver and systemic chemotherapy traditionally
      has had only limited efficacy, there has been increasing interest in locoregional
      therapy. Although locoregional therapy may include intra-arterial therapies,
      stereotactic radiotherapy, hepatic artery pump therapy, or ablation, most data
      are limited. The purpose of this article was to provide a multidisciplinary
      appraisal of the current therapeutic approaches to ICC.

PMID- 23963844
TI  - Surface adsorption considerations when working with amyloid fibrils in multiwell
      plates and Eppendorf tubes.
AB  - The accumulation of cross-beta-sheet amyloid fibrils is the hallmark of amyloid
      diseases. Recently, we reported the discovery of amyloid disaggregase activities
      in extracts from mammalian cells and Caenorhabditis elegans. However, we have
      discovered a problem with the interpretation of our previous results as Abeta
      disaggregation in vitro. Here, we show that Abeta fibrils adsorb to the plastic
      surface of multiwell plates and Eppendorf tubes. This adsorption is markedly
      increased in the presence of complex biological mixtures subjected to a
      denaturing air-water interface. The time-dependent loss of thioflavin T
      fluorescence that we interpreted previously as disaggregation is due to increased
      adsorption of Abeta amyloid to the surfaces of multiwell plates and Eppendorf
      tubes in the presence of biological extracts. As the proteins in biological
      extracts denature over time at the air-water interface due to agitation/shaking,
      their adsorption increases, in turn promoting adsorption of amyloid fibrils. We
      delineate important control experiments that quantify the extent of amyloid
      adsorption to the surface of plastic and quartz containers. Based on the results
      described in this article, we conclude that our interpretation of the kinetic
      fibril disaggregation assay data previously reported in Bieschke et al., Protein
      Sci 2009;18:2231-2241 and Murray et al., Protein Sci 2010;19:836-846 is invalid
      when used as evidence for a disaggregase activity. Thus, we correct the two prior
      publications reporting that worm or mammalian cell extracts disaggregate Abeta
      amyloid fibrils in vitro at 37 degrees C (see Corrigenda in this issue of Protein
      Science). We apologize for misinterpreting our previous data and for any
      confounding experimental efforts this may have caused. 

PMID- 23963846
TI  - Healthy cities in Europe: editorial.

PMID- 23963847
TI  - Traditional food: a better compatibility with industry requirements.
AB  - The objective of this article is to summarise the main results of the TRUEFOOD
      Integrated project, which is supported by the European Commission in the European
      Framework Program 6 (FP6). This project started in 2006 and ended in 2010.
      TRUEFOOD aimed to improve quality and safety and introduce innovation into
      Traditional European Food production systems through research, demonstration,
      dissemination and training activities. It focuses on increasing value to both
      consumers and producers and on supporting the development of realistic business
      plans for all components of the food chain, using a farm-to-fork approach.

PMID- 23963848
TI  - Enhanced efficacy of superparamagnetic iron oxide nanoparticles against
      antibiotic-resistant biofilms in the presence of metabolites.
AB  - Antibiotic resistance and the lack of new antibacterial agents cause major
      challenges for the treatment of infections. Here, we describe a simple, broad
      spectrum, and low-cost dual-sided approach which uses superparamagnetic iron
      oxide particles (SPION) in combination with fructose metabolites as an
      alternative to existing antibacterial strategies. This strategy offers further
      improved efficacy of SPION against persistent gram-positive and gram-negative
      bacteria infections by manipulating the biofilm metabolic microenvironment and
      outperforms vancomycin (the antibiotic of last resort), creating a new
      nanotechnology-driven approach. 

PMID- 23963849
TI  - Vascular endothelial growth factor C expression is closely correlated with lymph
      node recurrence and poor prognosis in patients with early stage cervical cancer.
AB  - OBJECTIVES: To detect vascular endothelial growth factor (VEGF)-C mRNA expression
      in surgically resected tissues of 'pathologic N0' (pN0) cervical cancer; to
      investigate the relevance of VEGF-C mRNA expression to clinicopathological
      factors, lymph node recurrence and prognosis in early stage cervical cancer.
      METHODS: Patients with pN0 cervical cancer who successfully underwent radical
      hysterectomy with bilateral adnexectomy and bilateral pelvic lymphadenectomy were
      enrolled sequentially into this retrospective study. Reverse transcriptase
      polymerase chain reaction (RT-PCR) was performed to detect VEGF-C mRNA. RESULTS:
      Seventy-eight patients entered the study. VEGF-C mRNA was detected in 35 (44.87%)
      patients and was significantly correlated with tumour differentiation. VEGF-C
      mRNA expression was significantly associated with lymph node recurrence and poor
      overall survival 5 years after surgery. Multivariate analysis confirmed that VEGF
      C mRNA expression was an independent predictor for lymph node recurrence and
      unfavourable overall survival. CONCLUSIONS: These findings indicate that
      detection of VEGF-C mRNA has clinical potential as a predictor for identifying
      patients with pN0 cervical cancer at high risk of lymph node recurrence and poor
      prognosis.

PMID- 23963850
TI  - Clinical evaluation of thrombus aspiration combined with tirofiban in patients
      with acute myocardial infarction with elective percutaneous coronary
      intervention.
AB  - OBJECTIVE: To compare the efficacy and safety of combined treatment with thrombus
      aspiration and intracoronary tirofiban in patients with acute myocardial
      infarction (MI), with elective percutaneous coronary intervention (PCI). METHODS:
      Patients undergoing elective PCI during recovery from acute MI were randomized
      into two groups; the intervention group received thrombus aspiration and
      intracoronary tirofiban; the control group received conventional PCI. Baseline
      clinical characteristics, postoperative coronary blood flow (thrombolysis in
      myocardial infarction [TIMI] grade), TIMI myocardial perfusion (TMP) grade,
      no/slow reflow rate and cardiac function (measured by echocardiography 1 month
      postoperatively) were evaluated. Major adverse cardiac event rate and bleeding
      complications during surgery (and at 1 month and 1 year postoperatively) were
      also evaluated. RESULTS: A total of 80 patients were included. Postoperatively,
      the number of patients with TIMI flow grade 3 and the mean TMP grade were both
      significantly higher, and the no/slow reflow rate was significantly lower, in the
      intervention group versus the control group. Echocardiography indicated that
      cardiac function was significantly improved in the intervention group compared
      with the control group. There were no major complications in either study group.
      CONCLUSION: Thrombus aspiration combined with intracoronary tirofiban during
      recovery from acute MI was effective and relatively well tolerated.

PMID- 23963851
TI  - A novel mutation of the high-temperature requirement A serine peptidase 1 (HTRA1)
      gene in a Chinese family with cerebral autosomal recessive arteriopathy with
      subcortical infarcts and leukoencephalopathy (CARASIL).
AB  - OBJECTIVE: Mutations in the high-temperature requirement A serine peptidase 1
      (HTRA1) gene were studied in a Chinese family with cerebral autosomal recessive
      arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL).
      METHODS: Exons 1-9 of the HTRA1 gene were amplified and bidirectionally sequenced
      in a Chinese family with CARASIL. Mutation effects were analysed by three
      dimensional modelling of the serine protease HTRA1 protein. RESULTS: The proband
      was found to be homozygous for a novel missense mutation (c.854 C > T) identified
      in exon 4 of the HTRA1 gene; the parents of the proband were heterozygous for the
      same missense mutation. This c.854 C > T mutation resulted in a change from
      proline to leucine (p.P285L) in serine protease HTRA1, and was absent in 260
      control chromosomes. Three-dimensional models showed that the change from proline
      to leucine (p.P285L) could attenuate the hydrogen bond between S284 and S287
      residues, which might affect function of serine protease HTRA1. CONCLUSION:
      Discovery of a novel missense mutation (c.854C>T) associated with CARASIL expands
      the known CARASIL-related mutations in HTRA1.

PMID- 23963852
TI  - Serum microRNA-92 expression in patients with ovarian epithelial carcinoma.
AB  - OBJECTIVES: Studies have reported the significance of circulating microRNAs
      (miRNAs) as biochemical markers of cancer. Few reports demonstrate the
      significance of miRNAs in the serum of patients with ovarian epithelial carcinoma
      (EOC). The present study prospectively investigated the status of miRNA-92 (miR
      92) in the serum of EOC patients and healthy controls, and examined the potential
      usefulness of this molecule as a biomarker for EOC diagnosis. METHODS: Levels of
      miR-92 in serum samples from EOC patients and controls were measured by
      quantitative real time reverse transcription-polymerase chain reaction (RT-PCR).
      Associations between serum miR-92 concentrations and clinical parameters were
      assessed by Fisher's exact probability test. RESULTS: The serum concentration of
      miR-92 in EOC patients (n = 50) was significantly higher than in controls (n =
      50). There were significant correlations between miR-92 expression and regional
      lymph node involvement and clinical stage of the tumour. There was no significant
      association between expression of miR-92 and age. CONCLUSION: The detection of
      miR-92 levels in the serum might serve as a new tumour biomarker in the diagnosis
      and assessment of prognosis of EOC.

PMID- 23963853
TI  - Integration of autophagy and anoikis resistance in solid tumors.
AB  - Macroautophagy or autophagy is a lysosome-dependent process in which enzymatic
      degradation and recycling of cytosolic components occurred due to stressful
      conditions. This cellular arrangement imparts anoikis resistance in solid tumors.
      Anoikis, a special form of apoptosis occurring when cells detach from the
      extracellular matrix, is a critical mechanism in maintaining tissue homeostasis
      and development. Anoikis resistance facilitates tumorigenesis and metastasis.
      However, the complexity of the role of autophagy in tumor is underscored by
      evidence that autophagy can function as both a pro-survival or pro-death
      depending on the context and the stimuli, which are likely exploitable for tumor
      therapy. This review focuses on recent progress in understanding anoikis
      resistance and autophagy signaling, paying particular attention to its relevance
      in solid tumor metastasis.

PMID- 23963854
TI  - Falls and traumatic brain injury in adults under the age of sixty.
AB  - Falls are a significant cause of traumatic brain injury (TBI). There has been
      little research into falls resulting in a TBI in adults under the age of 60. The
      authors retrospectively analysed consecutive referrals to their community
      rehabilitation service between 2009 and 2012 in order to determine whether falls
      are a common cause of TBI in adults under 60, the different types of falls, the
      presence of alcohol at the time of the fall, and return to work following TBI.
      Falls accounted for 25 % of TBI. Ground-level falls and falls down stairs were
      the main causes of falls leading to TBI. Alcohol was present in 30 % of the
      falls. 44 % of individuals who had been working prior to their fall related-TBI
      had returned to work 1 year post-TBI. The authors conclude that falls amongst
      adults under sixty is an important cause of traumatic brain injury, and requires
      preventative and reduction strategies. 

PMID- 23963855
TI  - Implementation of HIV prevention interventions in resource limited settings: the
      partner project.
AB  - Evidence-based HIV prevention interventions have been translated to a variety of
      contexts across sub-Saharan Africa. Non-specialized community health center (CHC)
      staff members have been successfully engaged to deliver the interventions, which
      can be integrated into pre-existing HIV service programs in community-based
      health care delivery sites. This manuscript describes the process of implementing
      the Partner Project, a couples HIV risk reduction intervention, and examines the
      ability of CHC staff to achieve risk reduction outcomes comparable to those of
      the highly-trained research staff. The Partner Project was implemented within the
      HIV Counseling and Testing program in 6 urban community health clinics in Lusaka,
      Zambia. One hundred ninety-seven HIV-seroconcordant and -discordant couples were
      sequentially enrolled to the control group or to receive the intervention from
      partner research or CHC staff members. Couple members completed assessments on
      condom use, alcohol use, and intimate partner violence (IPV) at baseline, 6, and
      12 months follow-up. Sexual barrier use outcomes achieved by the CHC staff were
      comparable to or better than those achieved by the Partner Project research
      staff, and both were superior to the control group. A reduction in IPV was
      observed for the entire sample, although no change in alcohol use was observed.
      Implementation of HIV prevention interventions at the community level should take
      advantage of existing resources available within the CHC staff. This is
      especially relevant in resource limited settings as consideration of the
      financial and clinical requirements of intervention programs is essential to the
      achievement of successful program implementation. 

PMID- 23963856
TI  - Detection of hypermethylated fibrillin-1 in the stool samples of colorectal
      cancer patients.
AB  - Prior studies have demonstrated that analysis of gene promoter methylation in
      stool samples may be a potential biomarker for noninvasive colorectal cancer
      detection. Aberrant methylation in gene promoter is common in various cancers,
      and epigenetic alterations can result in down-regulation or silence of gene
      expression. Recently, hypermethylation of fibrillin-1 (FBN1) was reported to be
      associated with colorectal cancer (CRC). In this study, we examined the
      methylation status of FBN1 in stool samples to test CRC. For the purpose of
      colorectal cancer detection, we investigated FBN1 hypermethylation in the tissue
      and stool samples of colorectal cancer patients using methylation-specific
      polymerase chain reaction. The result is that out of 75 patients with colorectal
      cancer, 59 (78.7%) exhibited hypermethylated FBN1 in their tumor tissue DNA. We
      next detected the methylation status of FBN1 in the stool DNA of these patients.
      The hypermethylated FBN1 occurred in 72% (54/75) of these patients in their stool
      samples and occurred in 6.7% (2/30) of healthy people (P < 0.001). The results
      indicated 72.0% sensitivity and 93.3% specificity of the test for detecting CRC
      by using stool samples. So, the study reveals that hypermethylation status in the
      promoter of FBN1 is a high specific and sensitive biomarker for colorectal
      cancer, and detecting hypermethylated FBNI in stool samples is a noninvasive and
      useful method for screening colorectal cancer.

PMID- 23963857
TI  - Unusual case of metachronous EBV-associated B-cell and NK/T-cell lymphoma
      mimicking polymyositis-diagnostic challenges and pitfalls.

PMID- 23963859
TI  - Letter to the Editor - responses to Weisntein D, Simon M, Yehezkel E, Laron Z,
      Werner H. Insulin analogues display IGF-I-like mitogenic and antiactivity in
      cultured cancer cells.
AB  - We thank the team of Eli Lilly and Company for their critical appraisal of our
      study and for giving us the opportunity to clarify a number of points [1]. We
      agree with Kazda et al. that randomized clinical trials will best address any
      direct relationship between insulin analogues and cancer in man. We do not
      question the fact that tight control of blood glucose has dramatically advanced
      the lives of patients with diabetes. This article is protected by copyright. All
      rights reserved.

PMID- 23963858
TI  - Impact of pneumococcal conjugate vaccines on microbial epidemiology and clinical
      outcomes of acute otitis media.
AB  - Acute otitis media (AOM) is the leading bacterial infection in childhood and the
      main reason for antibiotic prescriptions in children. The success of pneumococcal
      conjugate vaccines (PCVs) in reducing invasive pneumococcal disease has been
      demonstrated in many studies. Because Streptococcus pneumoniae is one of the two
      main bacterial species implicated in AOM, the incidence and characteristics of
      AOM might also be modified by PCVs. Pre-licensure controlled studies showed that
      the effect was modest. However, after PCV7 implementation, the impact on the AOM
      burden appeared to be more marked, despite the fact that serotype replacement in
      the nasopharynx was almost complete. Most data on the impact of PCVs on
      nasopharyngeal flora have been drawn from studies with PCV7. No difference was
      observed with PCV10 compared with PCV7 concerning S. pneumoniae and Haemophilus
      influenza carriage. For PCV13 compared with PCV7, additional reduction of
      carriage of serotypes 1, 6A, 7F, 6C, 19A, and 19F was observed, but for the other
      serotypes, the two PCVs seemed to have the same effect. 

PMID- 23963860
TI  - Pollination ecology in the narrow endemic winter-flowering Primula allionii
      (Primulaceae).
AB  - Reduction of pollen flow can affect plant abundance and population viability and
      cause selection on plant mating system and floral traits. Little is known on the
      effect of this phenomenon in species naturally restricted to small and isolated
      habitats, that may have developed strategies to cope with long-term isolation and
      small population size. We investigated the pollination ecology of the endemic
      distylous winter-flowering P. allionii to verify the possible limitation of
      female fitness due to reduced pollinator visits. We recorded a higher production
      of pollen grains in long-styled morph, and a higher seed set in short-styled
      morph. The high intra-morph variability of sexual organ position may explain the
      hybridization phenomena allowing and easier intra-morph pollination. The fruit
      set is constant, although its winter-flowering period might decrease pollen
      transfer. Nevertheless, the lower competition for pollinators with neighbouring
      plants and the long-lasting anthesis may offset its reproductive success. Even if
      our results show no evidence of imminent threats, changes in plant-pollinator
      interactions might increase inbreeding, resulting in an increased extinction
      risk. 

PMID- 23963861
TI  - Molecular pathways: induction of polyploidy as a novel differentiation therapy
      for leukemia.
AB  - Differentiation therapy has emerged as a powerful way to target specific
      hematologic malignancies. One of the best examples is the use of all-trans
      retinoic acid (ATRA) in acute promyelocytic leukemia (APL), which has
      significantly improved the outcome for patients with this specific form of acute
      myeloid leukemia (AML). In considering how differentiation therapy could be used
      in other forms of AML, we predicted that compounds that induce terminal
      differentiation of megakaryocytes would be effective therapies for the
      megakaryocytic form of AML, named acute megakaryocytic leukemia (AMKL). We also
      speculated that such agents would reduce the burden of abnormal hematopoietic
      cells in primary myelofibrosis and alter the differentiation of megakaryocytes in
      myelodysplastic syndromes. Using a high-throughput chemical screening approach,
      we identified small molecules that promoted many features of terminal
      megakaryocyte differentiation, including the induction of polyploidization, the
      process by which cells accumulate DNA to 32N or greater. As the induction of
      polyploidization is an irreversible process, cells that enter this form of the
      cell cycle do not divide again. Thus, this would be an effective way to reduce
      the tumor burden. Clinical studies with polyploidy inducers, such as aurora
      kinase A inhibitors, are under way for a wide variety of malignancies, whereas
      trials specifically for AMKL and PMF are in development. This novel form of
      differentiation therapy may be clinically available in the not-too-distant
      future. Clin Cancer Res; 19(22); 6084-8. (c)2013 AACR. 

PMID- 23963863
TI  - Simultaneous enhancement of brightness, efficiency, and switching in RGB organic
      light emitting transistors.
AB  - An innovative design strategy for light emitting field effect transistors
      (LEFETs) to harvest higher luminance and switching is presented. The strategy
      uses a non-planar electrode geometry in tri-layer LEFETs for simultaneous
      enhancement of the key parameters of quantum efficiency, brightness, switching,
      and mobility across the RGB color gamut. 

PMID- 23963862
TI  - Cumulative genetic risk predicts platinum/taxane-induced neurotoxicity.
AB  - PURPOSE: The combination of a platinum and taxane are standard of care for many
      cancers, but the utility is often limited due to debilitating neurotoxicity. We
      examined whether single-nucleotide polymorphisms (SNP) from annotated candidate
      genes will identify genetic risk for chemotherapy-induced neurotoxicity. PATIENTS
      AND METHODS: A candidate-gene association study was conducted to validate the
      relevance of 1,261 SNPs within 60 candidate genes in 404 ovarian cancer patients
      receiving platinum/taxane chemotherapy on the SCOTROC1 trial. Statistically
      significant variants were then assessed for replication in a separate 404 patient
      replication cohort from SCOTROC1. RESULTS: Significant associations with
      chemotherapy-induced neurotoxicity were identified and replicated for four SNPs
      in SOX10, BCL2, OPRM1, and TRPV1. The population attributable risk for each of
      the four SNPs ranged from 5% to 35%, with a cumulative risk of 62%. According to
      the multiplicative model, the odds of developing neurotoxicity increase by a
      factor of 1.64 for every risk genotype. Patients possessing three risk variants
      have an estimated OR of 4.49 (2.36-8.54) compared to individuals with 0 risk
      variants. Neither the four SNPs nor the risk score were associated with
      progression-free survival or overall survival. CONCLUSIONS: This study shows that
      SNPs in four genes have a significant cumulative association with increased risk
      for the development of chemotherapy-induced neurotoxicity, independent of patient
      survival.

PMID- 23963864
TI  - Incidence and prognosis of gastroesophageal cancer in rural, urban, and
      metropolitan areas of the United States.
AB  - BACKGROUND: The objective of this study was assess differences in the incidence,
      late-stage diagnosis, and prognosis of squamous cell carcinoma of the esophagus
      (SCCE), adenocarcinoma of the esophagus (AE), and adenocarcinoma of the gastric
      cardia (AGC) in metropolitan, urban, and rural areas in the United States.
      METHODS: The authors identified 29,527 patients with SCCE, AE, or AGC who were
      reported to the Surveillance, Epidemiology, and End Results Program between 2004
      and 2009. Incidence estimates for each malignancy were compared across
      metropolitan, urban, and rural areas. Multivariable logistic regression models
      were applied to evaluate the association between residential setting and late
      (distant-stage) diagnosis, and the results were reported as adjusted odds ratios
      and 95% confidence intervals (CIs). Cox proportional hazard models were used to
      examine the association between residential setting and cause-specific survival.
      RESULTS: When residential setting was analyzed using metropolitan population
      centers as the reference category, the incidence of AE was higher in urban areas
      (rate ratio [RR], 1.13; 95% CI, 1.06-1.20) and rural areas (RR, 1.15; 95% CI,
      1.05-1.25), whereas the incidence of SCCE was lower in rural areas (RR, 0.80; 95%
      CI, 0.70-0.91). Rural patients were less likely to be diagnosed with stage IV AE
      compared with patients residing in metropolitan areas (odds ratio, 0.79; 95% CI,
      0.65-0.97). No differences in prognosis were observed when patients from large
      metropolitan centers were compared with their rural counterparts. CONCLUSIONS:
      The current findings indicated that preconceptions regarding disparities in the
      time of diagnosis and survival between patients from metropolitan and rural areas
      in the United States are either unwarranted or out of date, at least with respect
      to gastroesophageal cancers.

PMID- 23963865
TI  - Street food on the move: a socio-philosophical approach.
AB  - In the last decade social and hard scientists have increasingly analysed the
      issue of street food, which is now become a question of common concern in
      international public discourse. However, considering present literature and
      investigations, a socio-philosophical approach to the issue under examination has
      been until now not properly developed. For this reason, this paper is not aimed
      at improving an empirical research on street food. Rather, it is interested in
      developing an innovative methodological approach, which assumes transcultural,
      intersectional, diachronic and interdisciplinary viewpoints in the analysis of
      the phenomenon. Taking as a background the very rich theoretical and empirical
      literature on food (which is difficult to be summarised in a few pages), the
      paper intends to strengthen a conceptual analysis of street food as a social
      construction and historical symbol, opening up new theoretical, comparative,
      sociological and pragmatic perspectives. The normative and critical content of
      street food refers thus ex negativo to the right to the quality of food and to
      have a decent and peaceful existence in both post-colonial and post-industrial
      societies in an interconnected global age.

PMID- 23963866
TI  - Aerobiological, clinical, and immunobiochemical studies on Alstonia scholaris
      pollen from Eastern India.
AB  - Alstonia scholaris or Indian devil tree is a common, evergreen, tropical tree of
      the Apocynaceae family. The objectives of this study were (a) to observe the
      seasonal variation of A. scholaris pollen in the atmosphere of an industrial and
      rural area of West Bengal, India by conducting a 2-year aerobiological survey
      with a Burkard personal volumetric sampler, (b) to study its allergenicity in the
      local population by in vivo (skin-prick test) and in vitro tests (enzyme-linked
      immunosorbent assay and dot blotting), (c) to identify the immunoglobulin E (IgE)
      binding proteins present in the pollen extract (sodium dodecyl sulphate
      polyacrylamide gel electrophoresis and immunoblotting), (d) to study its chemical
      composition. A. scholaris pollen were present in the air from September until
      November. They contained 14.3 % carbohydrate, 9.2 % lipid, and 4.3 % protein.
      Among 140 respiratory allergic local patients, 28.57 % showed positive skin
      reaction to A. scholaris pollen extract. Twelve protein bands in the range of
      94.4-13.3 kDa were observed in the pollen extract. Seven IgE-binding proteins
      were found. Among them, one component of 29.9 kDa was the most important in A.
      scholaris pollen extract. This component could be purified and would be helpful
      in the diagnosis and therapy of A. scholaris pollen-susceptible patients. 

PMID- 23963867
TI  - The economic burden of toxicities associated with cancer treatment: review of the
      literature and analysis of nausea and vomiting, diarrhoea, oral mucositis and
      fatigue.
AB  - Side effects or toxicities are frequent, undesirable companions of almost all
      forms of non-surgical cancer therapy. It is unusual for patients to complete
      treatment with radiation or chemotherapy without experiencing at least one form
      of therapy-associated tissue injury or systemic side effect. Often, toxicities do
      not occur as solitary events; rather, they result in clusters of symptoms that
      share a common biological aetiology. Like any disease, cancer treatment-related
      toxicities (CTRTs) vary in their severity. But, in contrast to most diseases in
      which incidence is described as being present or absent, the current approach to
      CTRT typically limits reporting to severe cases only. Not only does this dilute
      the frequency with which CTRTs occur, but it also undermines our ability to
      determine the full burden of their impact and to accurately assess the cost
      effectiveness of potential toxicity interventions. In this article, we report the
      results of a directed literature review for the years 2000-2012, in which we
      studied and compared three tissue-based toxicities (nausea and vomiting,
      diarrhoea, and oral mucositis) and one systemic toxicity (fatigue). Our results
      confirm the heavy burden of resource use and cost associated with CTRTs. The
      inclusion of fatigue in our analysis provided an opportunity to compare and
      contrast a toxicity in which there are both acute and chronic consequences. Our
      findings also demonstrate a number of challenges to, and opportunities for,
      future study. Among the most obvious are the lack of provider consistency in
      diagnosis and grading, especially when there is no global agreement on severity
      scales. Compounding this inconsistency is the disconnect between healthcare
      providers and patients that exists when describing toxicity severity and impact.
      In many cases, cancer can be thought of as a chronic disease that requires
      prolonged but episodic treatment once the acute disease is eradicated. This
      change reflects increasing treatment successes, but it also implies that the
      burden of CTRTs will be expanded and prolonged. Creation of hierarchical
      attribution of costs in the presence of simultaneous CTRTs, accurate coding, and
      consistent tracking tools for toxicities will be imperative for effective
      appraisal of the costs associated with cancer treatment regimen toxicities. 

PMID- 23963868
TI  - Outcomes of esophagectomy for esophageal achalasia in the United States.
AB  - BACKGROUND: While the outcomes after Heller myotomy have been extensively
      reported, little is known about patients with esophageal achalasia who are
      treated with esophagectomy. METHODS: This was a retrospective analysis using the
      Nationwide Inpatient Sample over an 11-year period (2000-2010). Patients admitted
      with a primary diagnosis of achalasia who underwent esophagectomy (group 1) were
      compared to patients with esophageal cancer who underwent esophagectomy (group 2)
      during the same time period. Primary outcome was in-hospital mortality. Secondary
      outcomes included length of stay, postoperative complications, and total hospital
      charges. A propensity-matched analysis was conducted comparing the same outcomes
      between group 1 and well-matched controls in group 2. RESULTS: Nine hundred sixty
      three patients with achalasia and 18,003 patients with esophageal cancer
      underwent esophagectomy. The propensity matched analysis showed a trend toward a
      higher mortality in group 2 (7.8 vs. 2.9 %, p = 0.08). Postoperative length of
      stay and complications were similar in both groups. Total hospital charges were
      higher for the achalasia group ($115,087 vs. $99, 654.2, p = 0.006). CONCLUSION:
      This is the largest study to date examining outcomes after esophagectomy in
      patients with achalasia. Based on our findings, esophagectomy can be considered a
      safe option, and surgeons should not be hindered by a perceived notion of
      prohibitive operative risk in this patient population.

PMID- 23963869
TI  - Effects of subclass change on the structural stability of chimeric, humanized,
      and human antibodies under thermal stress.
AB  - To address how changes in the subclass of antibody molecules affect their
      thermodynamic stability, we prepared three types of four monoclonal antibody
      molecules (chimeric, humanized, and human) and analyzed their structural
      stability under thermal stress by using size-exclusion chromatography,
      differential scanning calorimetry (DSC), circular dichroism (CD), and
      differential scanning fluoroscopy (DSF) with SYPRO Orange as a dye probe. All
      four molecules showed the same trend in change of structural stability; the order
      of the total amount of aggregates was IgG1 < IgG2 < IgG4. We thus successfully
      cross-validated the effects of subclass change on the structural stability of
      antibodies under thermal stress by using four methods. The T(h) values obtained
      with DSF were well correlated with the onset temperatures obtained with DSC and
      CD, suggesting that structural perturbation of the CH2 region could be monitored
      by using DSF. Our results suggested that variable domains dominated changes in
      structural stability and that the physicochemical properties of the constant
      regions of IgG were not altered, regardless of the variable regions fused.

PMID- 23963870
TI  - The Cellient automated cell block system is useful in the differential diagnosis
      of atypical glandular cells in Papanicolaou tests.
AB  - BACKGROUND: Atypical glandular cells (AGC) is a very important diagnosis in
      gynecological cytology. In the current study, the authors investigated the
      usefulness of Cellient cell blocks (CB) for characterizing AGC on Papanicolaou
      (Pap) tests. METHODS: A total of 148 patients with an AGC diagnosis based on Pap
      tests by cytotechnologists and referred to cytopathologists were studied. Among
      these patients, there were 68 patients with CB preparations and 80 patients with
      Pap tests only (TP-AGC group). Follow-up results by Pap tests or biopsies were
      obtained in 117 of 148 patients. The median follow-up was 13 months (range, 1
      month-36 months). RESULTS: Of the 68 patients with CBs, 31 (46%) were
      reclassified as negative for dysplasia or low-grade intraepithelial lesion; 30
      patients (44%) retained a diagnosis of AGC (CB-AGC group); and 7 patients (10%)
      were given specific diagnoses of high-grade intraepithelial lesion (3 patients),
      endocervical adenocarcinoma in situ (1 patient), and invasive adenocarcinoma (3
      patients). On follow-up, the CB-AGC group was found to have a significantly lower
      rate of negative/low-grade squamous intraepithelial lesion diagnoses compared
      with the TP-AGC group (55% vs 85%; P= .006). The CB-AGC group had a significantly
      higher rate of endocervical or endometrial adenocarcinoma compared with the TP
      AGC group (36% vs 8%; P= .003) at the time of follow-up. The rates of high-grade
      squamous intraepithelial lesion were not found to be statistically different
      between these 2 groups (9% vs 7%; P= .66). CONCLUSIONS: The Cellient CB is a
      useful technique to further categorize a diagnosis of AGC on Pap tests. Using the
      Cellient CB system, the pathologist has the ability to improve the diagnostic
      accuracy of AGC so that unnecessary colposcopic evaluation or biopsies can be
      avoided.

PMID- 23963871
TI  - Selective lateral pelvic lymph node dissection in patients with advanced low
      rectal cancer treated with preoperative chemoradiotherapy based on pretreatment
      imaging.
AB  - BACKGROUND: The significance of lateral pelvic lymph node (LPLN) metastasis in
      advanced low rectal cancer treated with preoperative chemoradiotherapy (CRT)
      remains unclear. The objective of this study was to evaluate the outcomes of
      selective LPLN dissection (LPLD) based on the pretreatment imaging in patients
      with advanced low rectal cancer treated with preoperative CRT. METHODS: We
      reviewed 127 consecutive patients with clinical stage II-III low rectal cancer
      below the peritoneal reflection who underwent preoperative CRT and curative
      resection. LPLD was performed in patients with suspected LPLN metastasis based on
      MDCT or MRI before CRT (LPLD group, N = 38), and only total mesorectal excision
      (TME) was performed in patients without suspected LPLN metastasis (TME group, N =
      89). Clinical characteristics and the oncological outcome were compared between
      groups. RESULTS: The median tumor-to-anal verge distance was 40 mm in both
      groups. The median maximum long-axis LPLN diameter before CRT was 0 mm in the TME
      group and 10.5 mm in the LPLD group. Pathological LPLN metastasis was confirmed
      in 25 patients (66 %) in the LPLD group. Local recurrence at LPLN developed in 3
      patients (3.4 %) in the TME group and in none (0 %) of the LPLD group.
      Multivariate analysis showed that only ypN was an independent prognostic factor
      for relapse-free survival (RFS), but LPLN metastasis was not associated with poor
      RFS. CONCLUSIONS: The incidence of LPLN metastasis is high even after
      preoperative CRT, and LPLD might improve local control and survival of patients
      with LPLN metastasis in advanced low rectal cancer treated with preoperative CRT.

PMID- 23963872
TI  - Stimulating erythropoiesis in neonates.

PMID- 23963873
TI  - Sun protection attitudes and behaviours among first generation Australians with
      darker skin types: results from focus groups.
AB  - Despite residing in a country that has the highest rates of skin cancer in the
      world, little is known about the knowledge, attitudes and sun protection
      practices of first generation Australian-born individuals with olive and darker
      skin types. Six focus groups with first generation Australian-born individuals of
      Asian, Mediterranean, Middle Eastern and Indian background were conducted.
      Participants had good knowledge of the dangers of skin cancer. Most correctly
      perceived darker skin types as protective and believed they were at low risk of
      skin cancer. Most participants could recall high profile mass media sun
      protection campaigns. Several participants suggested that greater representation
      of ethnic minorities and/or individuals with darker skin types would increase the
      personal relevance of campaigns. Beliefs that sun protection is not necessary on
      the basis of skin type highlights the need for further studies to explore
      fundamental differences in attitudes and practices between those with olive and
      darker skin and the general Australian population. 

PMID- 23963874
TI  - Impact of navigation on knowledge and attitudes about clinical trials among
      Chinese patients undergoing treatment for breast and gynecologic cancers.
AB  - Racial, ethnic and economic disparities in cancer rates, outcomes, and clinical
      trials participation persist despite significant research. We examined barriers
      to clinical trials enrollment among Chinese patients, and developed a navigation
      program for Chinese gynecologic and breast cancer patients. Six bilingual
      navigators were trained and a navigator assigned to each patient for at least 2
      months. All patients received a clinical trials booklet in Chinese and English.
      Data collection included pre-and post-navigation surveys, intake forms, and
      documentation of navigation encounters. Between July 2010 and May 31, 2011, we
      recruited 28 breast and gynecologic cancer patients. Patients averaged 317 min of
      navigation (range 63-1,852) during 8 sessions (range 3-28). They improved in 4 of
      10 true-false knowledge statements about clinical trials. A patient navigation
      program for Chinese-speaking cancer patients is feasible. It results in high
      patient satisfaction rates and modest improvements in clinical trials knowledge
      and participation.

PMID- 23963875
TI  - Potential secondary inoculum sources of Botrytis cinerea and their influence on
      bunch rot development in dry Mediterranean climate vineyards.
AB  - BACKGROUND: Epidemiological studies have described the life cycle of B. cinerea
      in vineyards. However, there is a lack of information on the several infection
      pathways and the quantitative relationships between secondary inoculum and bunch
      rot at harvest. RESULTS: Over two seasons, different spray programmes were used
      to determine key phenological stages for bunch rot development. Secondary
      inoculum sources within the bunch were also studied. The relative importance of
      flowering was evidenced in the given conditions, as treatments that included two
      fungicide applications at flowering were the most effective. In 2010, under
      conducive meteorological conditions for B. cinerea development after veraison, an
      extra application provided significantly higher control. Infections of necrotic
      tissues inside the bunch and latent infections developed mainly during flowering,
      while very low quantities of B. cinerea conidia were recovered from the fruit
      surface at veraison. Regression analysis correlated the incidence of latent
      infections and B. cinerea incidence on calyptras and aborted fruits at veraison
      with incidence of Botrytis bunch rot at harvest, presenting R2 = 0.95 for the
      overall regression model. CONCLUSION: This work points out key phenological
      stages during the season for bunch rot and B. cinerea secondary inoculum
      development and relates quantitatively inoculum sources at veraison to bunch rot
      at harvest. Recommendations for field applications of antibotrytic products are
      also suggested.

PMID- 23963876
TI  - Female-to-male transmasculine adult health: a mixed-methods community-based needs
      assessment.
AB  - BACKGROUND: There is a dearth of health research about transgender people.
      OBJECTIVES: This mixed-methods study sought to formatively investigate the health
      and perceived health needs of female-to-male transmasculine adults. DESIGN: A
      cross-sectional quantitative needs assessment (n = 73) and qualitative open-ended
      input (n = 19) were conducted in June 2011. A latent class analysis modeled six
      binary health indicators (depression, alcohol use, current smoking, asthma,
      physical inactivity, overweight status) to identify clusters of presenting health
      issues. RESULTS: Four clusters of health indicators emerged: (a) depression; (b)
      syndemic (all indicators); (c) alcohol use, overweight status; and (d) smoking,
      physical inactivity, overweight status. Transphobic discrimination in health care
      and avoiding care were each associated with membership in the syndemic class.
      Qualitative themes included personal health care needs, community needs, and
      resilience and protective factors. CONCLUSIONS: Findings fill an important gap
      about the health of transmasculine communities, including the need for public
      health efforts that holistically address concomitant health concerns.

PMID- 23963877
TI  - The cumulative risk of false-positive results in the Norwegian Breast Cancer
      Screening Program: updated results.
AB  - BACKGROUND: Some false-positive results are inevitable in mammographic screening,
      but the impact of false-positive findings on the program and the participants is
      a disadvantage of screening. The objective of the current study was to estimate
      the cumulative risk of a false-positive result over 10 biennial screening
      examinations and the cumulative risk of undergoing an invasive procedure with a
      benign outcome in women screened between the ages of 50 years to 69 years.
      METHODS: A retrospective cohort study was performed in 231,310 women aged 50
      years to 51 years at the time of first mammography screening who underwent
      715,311 screening mammograms in the Norwegian Breast Cancer Screening Program
      from 1996 through 2010. Generalized linear mixed models were used to estimate the
      probability of a false-positive screening result and to compute the cumulative
      false-positive risk for up to 10 biennial screening examinations. RESULTS: The
      cumulative false-positive risk after 20 years of biennial screening for women who
      initiated screening aged 50 years to 51 years was 20.0% (95% confidence interval
      [95% CI], 19.7%-20.4%). The cumulative risk of undergoing an invasive procedure
      with a benign outcome for the same group of women was 4.1% (95% CI, 3.9%-4.3%).
      The cumulative risk of undergoing a fine-needle aspiration cytology, core needle
      biopsy, or open biopsy with a benign outcome was 1.4% (95% CI, 1.3%-1.5%), 2.0%
      (95% CI, 1.9%-2.1%), and 0.16% (95% CI, 0.13%-0.19%), respectively. CONCLUSIONS:
      One in every 5 women will be recalled for further assessment with a negative
      outcome if they attend biennial mammographic screening between ages 50 years to
      69 years. The risk of an invasive procedure with a benign outcome is
      approximately 4%. It is important to communicate the existence and extent of this
      risk to the target group and to reduce to a minimum the waiting times between
      screening and further assessment.

PMID- 23963878
TI  - Effectiveness and safety of rabbit anti-thymocyte globulin in Japanese patients
      with aplastic anemia.
AB  - Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and
      cyclosporine A is the standard treatment for aplastic anemia (AA). The ATG
      formulation in Japan was changed from horse ATG [Lymphoglobulin((r)) (LG)] to
      rabbit ATG [Thymoglobulin((r)) (TG)] in 2009. Since then, 12 patients with AA
      have been treated with TG. Here, we summarize the effectiveness and safety of TG
      in comparison with data from 14 AA patients treated with LG before April 2009.
      One subject treated with LG but none treated with TG terminated the treatment due
      to a grade III adverse effect. The overall 6-month response rate after IST was
      similar for LG and TG (67 and 75 %). Infection was noted in five (38 %) and four
      (33 %) subjects treated with LG and TG, respectively. The initial response rate
      was significantly higher in the early-treatment group treated within a year of
      diagnosis than in the late-treatment group, who were treated more than a year
      after diagnosis (85 vs. 29 %, respectively), as reported previously, without
      apparent differences between the LG and TG groups. We conclude that TG at a dose
      of 2.5 mg/kg/day for 5 days is effective and safe in Japanese patients with AA. 

PMID- 23963879
TI  - Orientation-specific attachment of polymeric microtubes on cell surfaces.
AB  - Tubular particles presenting heterogeneous regions of chemistry on the tube-ends
      versus the side are fabricated and are shown to control the particle orientation
      on the surface of live lymphocytes. Controlling the orientation of anisotropic
      microparticles on cell surfaces is of interest for biomedical applications and
      drug delivery in particular, since it can be used to promote or resist particle
      internalization. 

PMID- 23963880
TI  - Relationship between 5' UTR length and gene expression pattern in chicken.
AB  - The chicken (Gallus gallus) is an important model organism that bridges the
      evolutionary gap between mammals and non-amniote vertebrates. Here, we carried
      out a systematic study of the relationship between 5' UTR length and gene
      expression pattern in the chicken genome. We found that gene 5' UTRs lengths show
      a negative correlation with gene expression levels and gene expression breadths
      significantly. The relevance of 5' UTR length to expression pattern can not be a
      consequence of transcription-associated mutations. We also found that gene 5' UTR
      length shows a weakly positive correlation with gene tissue specificity. Another
      intriguing finding is that genes with 5' UTR length <30 bp have highest
      expression level, highest expression breadth, and lowest tissue specificity in
      chicken. We argued that selection is likely involved in shaping 5' UTR length in
      the chicken genome.

PMID- 23963881
TI  - Traditional foods and food systems: a revision of concepts emerging from
      qualitative surveys on-site in the Black Sea area and Italy.
AB  - BACKGROUND: The European FP7 BaSeFood project included a traditional food study
      contextually analysing their function in local food systems to stimulate
      consumers' awareness and indicate co-existence options for different scale
      exploitation. Background concepts were (1) the available traditional foods
      definitions; (2) the theoretical background of food quality perceptions; and (3)
      the different levels of food functions. METHODS: Field investigations were
      carried out by face-to-face in-depth qualitative interviews with local
      stakeholders, in the Black Sea region and Italy, on all aspects of traditional
      food production chains: raw materials, products, processes and perceptions.
      Critical and intercultural comparisons represented the basis of data analysis.
      RESULTS: Eight hundred and thirty-nine foods were documented. The direct
      experience perception of traditional food value observed in local contexts is
      somewhat contrasting with the present European tendency to communicate
      traditional food nature through registration or proprietary standards.
      Traditional foods are generally a combination of energetic staples with other
      available ingredients; their intrinsic variability makes the definition of
      'standard' recipes little more than an artefact of convenience; cross-country
      variations are determined by available ingredients, social conditions and
      nutritional needs. Commercial production requires some degree of raw material and
      process standardisation. New technologies and rules may stimulate traditional
      food evolution, but may also represent a barrier for local stakeholders. A trend
      to work within supply chains by local stakeholders was detected. Specific health
      promoting values were rarely perceived as a fundamental character. The stable
      inclusion of traditional food systems in present food supply chains requires a
      recovery of consumers' awareness of traditional food quality appreciation.

PMID- 23963882
TI  - Revision surgery for treatment of weight regain after Roux-en-Y gastric bypass.
AB  - BACKGROUND: This study aims to evaluate results on revision surgery for weight
      regain after gastric bypass, based on surgical technique and follow-up. METHODS:
      This study is a retrospective analysis of 29 patients who presented weight regain
      on follow-up after more than 5 years, divided into four groups according to
      revision surgery type: group 1 (n = 9) includes patients who underwent an
      increase in the length of the alimentary limb to 200 cm; group 2 (n = 13) are
      patients who underwent an increase in the length of the alimentary limb and
      placing of a silicon ring; group 3 (n = 2) are patients who underwent an increase
      in the length of the alimentary limb and gastric plication, and group 4 (n = 5)
      are patients who underwent gastric plication and placing of a silicon ring.
      RESULTS: The average preoperative weight before revision surgery was 117.8 kg,
      and the average postoperative follow-up for revision surgery was 13.7 months.
      Weight loss after revision surgery was observed in all groups but was greater in
      patients with longer revisional postoperative follow-up. Patients who underwent
      placing of a silicon ring presented greater weight loss than those who had had
      such a band since the original gastric bypass operation. CONCLUSIONS: Data
      suggest that revision surgery may be a useful tool in achieving weight loss in
      patients presenting weight regain following gastric bypass, obesity, bariatric
      surgery, gastric bypass, weight regain, and revision surgery.

PMID- 23963883
TI  - Osteoporosis in the elderly.
AB  - Osteoporosis is predominantly a condition of the elderly with a consequent
      increase in bone fragility and susceptibility to fracture. A number of clinical
      as well as biological studies have been pivotal in providing us with an
      understanding of the pathophysiology of this condition. This article discusses
      the current concepts of age-related osteoporosis. 

PMID- 23963884
TI  - Improved accuracy with 3D planning and patient-specific instruments during
      simulated pelvic bone tumor surgery.
AB  - In orthopaedic surgery, resection of pelvic bone tumors can be inaccurate due to
      complex geometry, limited visibility and restricted working space of the pelvis.
      The present study investigated accuracy of patient-specific instrumentation (PSI)
      for bone-cutting during simulated tumor surgery within the pelvis. A synthetic
      pelvic bone model was imaged using a CT-scanner. The set of images was
      reconstructed in 3D and resection of a simulated periacetabular tumor was defined
      with four target planes (ischium, pubis, anterior ilium, and posterior ilium)
      with a 10-mm desired safe margin. Patient-specific instruments for bone-cutting
      were designed and manufactured using rapid-prototyping technology. Twenty-four
      surgeons (10 senior and 14 junior) were asked to perform tumor resection. After
      cutting, ISO1101 location and flatness parameters, achieved surgical margins and
      the time were measured. With PSI, the location accuracy of the cut planes with
      respect to the target planes averaged 1 and 1.2 mm in the anterior and posterior
      ilium, 2 mm in the pubis and 3.7 mm in the ischium (p < 0.0001). Results in terms
      of the location of the cut planes and the achieved surgical margins did not
      reveal any significant difference between senior and junior surgeons (p = 0.2214
      and 0.8449, respectively). The maximum differences between the achieved margins
      and the 10-mm desired safe margin were found in the pubis (3.1 and 5.1 mm for
      senior and junior surgeons respectively). Of the 24 simulated resection, there
      was no intralesional tumor cutting. This study demonstrates that using PSI
      technology during simulated bone cuts of the pelvis can provide good cutting
      accuracy. Compared to a previous report on computer assistance for pelvic bone
      cutting, PSI technology clearly demonstrates an equivalent value-added for bone
      cutting accuracy than navigation technology. When in vivo validated, PSI
      technology may improve pelvic bone tumor surgery by providing clinically
      acceptable margins.

PMID- 23963885
TI  - Dynamics of translational friction in needle-tissue interaction during needle
      insertion.
AB  - In this study, a distributed approach to account for dynamic friction during
      needle insertion in soft tissue is presented. As is well known, friction is a
      complex nonlinear phenomenon. It appears that classical or static models are
      unable to capture some of the observations made in systems subjected to
      significant frictional effects. In needle insertion, translational friction would
      be a matter of importance when the needle is very flexible, or a stop-and-rotate
      motion profile at low insertion velocities is implemented, and thus, the system
      is repeatedly transitioned from a pre-sliding to a sliding mode and vice versa.
      In order to characterize friction components, a distributed version of the LuGre
      model in the state-space representation is adopted. This method also facilitates
      estimating cutting force in an intra-operative manner. To evaluate the
      performance of the proposed family of friction models, experiments were conducted
      on homogeneous artificial phantoms and animal tissue. The results illustrate that
      our approach enables us to represent the main features of friction which is a
      major force component in needle-tissue interaction during needle-based
      interventions. 

PMID- 23963886
TI  - Laser induced nitrogen enhanced titanium surfaces for improved osseo-integration.
AB  - The osseo-integration, corrosion resistance, and tribological properties of the
      commonly used bioimplant alloy Ti-6Al-4V were enhanced using a laser-based
      surface nitridation process. The biomedical properties of the laser nitrided Ti
      6Al-4V were investigated using experimental and computational methodologies.
      Electrochemical analysis of laser nitrided titanium in simulated body fluid (SBF)
      was performed to assess the biomedical characteristics in near-human body
      conditions. Additionally, the corrosive wear performance of these laser nitrided
      samples was evaluated using pin-on-disk geometry with a zirconia pin counter
      surface in SBF to mimic the biological scenario. Osteoblast studies were
      conducted to evaluate cell affinity towards titanium nitrided bioimplant
      material. Cells adhered to all substrates, with high viability. Initial cell
      adhesion was revealed by focal adhesion formation on all substrates. Cells can
      proliferate on samples treated with 1.89 and 2.12 * 10(6) J/m(2) laser
      conditions, while those treated with 1.70 * 10(6) J/m(2) inhibited proliferation.
      Thus, microstructural and phase observations, electrochemical analyses, corrosive
      wear evaluation, and cell behavior analysis of laser nitrided surface of
      bioimplant material (Ti-6Al-4V) indicated that laser nitriding greatly improves
      the performance of bioimplant material.

PMID- 23963887
TI  - Detecting the presence of target-site resistance to neonicotinoids and
      pyrethroids in Italian populations of Myzus persicae.
AB  - BACKGROUND: Myzus persicae is a key pest of peach, which in commercial orchards
      is mainly controlled by chemical treatments. Neonicotinoids represent the main
      control strategy, but resistance monitoring programmes in Southern Europe have
      shown the widespread presence of populations highly resistant to this insecticide
      class in peach orchards. Moreover, in Italy reports of neonicotinoid application
      failures are increasing. This work describes the status of the main target-site
      mutations associated with neonicotinoid and pyrethroid resistance in Italian
      populations collected in 2012. RESULTS: R81T mutation linked with neonicotinoid
      resistance was found in 65% of analysed aphids (35.5% with a homozygous resistant
      genotype). For the first time, R81T was found in samples collected from
      herbaceous hosts. Bioassays on a few genotyped populations also revealed the
      involvement of P450-based metabolic resistance. Only a few individuals without
      kdr (L1014F) and s-kdr (M918T) target-site mutations were collected. A new single
      nucleotide polymorphism in the s-kdr locus producing M918L substitution was
      found. CONCLUSION: Target-site resistance to neonicotinoids is common in
      specialised peach-growing areas, and it is spreading in other Italian regions and
      on herbaceous hosts. The high frequency of target-site mutations and data
      obtained from bioassays confirm the presence of multiple resistance mechanisms
      and suggest the importance of coordinated control strategies.

PMID- 23963888
TI  - Chronic myelomonocytic leukemia: 2013 update on diagnosis, risk stratification,
      and management.
AB  - DISEASE OVERVIEW: Chronic myelomonocytic leukemia (CMML) is a clonal
      hematopoietic stem cell disorder that is classified as a
      myelodysplastic/myeloproliferative neoplasm by the 2008 World Health Organization
      classification of hematopoietic tumors. It is characterized by absolute
      monocytosis (>1 * 109/L) in the peripheral blood that persists for at least 3
      months. DIAGNOSIS: The diagnosis of CMML rests on a combination of morphologic,
      histopathologic and chromosomal abnormalities in the bone marrow. It is important
      to exclude other myeloproliferative neoplasms and infectious/autoimmune
      conditions that can cause monocytosis. RISK STRATIFICATION: Several CMML-specific
      prognostic models incorporating novel mutations have been recently reported. The
      Mayo prognostic model classified CMML patients into three risk groups based on:
      increased absolute monocyte count, presence of circulating blasts, hemoglobin <10
      gm/dL and platelets <100 * 109/L. The median survival was 32 months, 18.5 months
      and 10 months in the low, intermediate, and high-risk groups, respectively. The
      Groupe Francophone des (GFM) score segregated CMML patients into three risk
      groups based on: age >65 years, WBC >15 * 109/L, anemia, platelets <100 * 109/L,
      and ASXL1 mutation status. After a median follow-up of 2.5 years, survival ranged
      from not reached in the low-risk group to 14.4 months in the high-risk group.
      RISK-ADAPTED THERAPY: The Food and Drug Administration has approved azacitidine
      and decitabine for the treatment of patients with CMML. An allogeneic stem cell
      transplant can potentially offer a curative option to a subset of CMML patients.
      It is hoped that with the discovery of several novel mutations, targeted
      therapies will become available in the near future.

PMID- 23963889
TI  - Phasing statistics for alpha helical membrane protein structures.
AB  - In this report we highlight the latest trends in phasing methods used to solve
      alpha helical membrane protein structures and analyze the use of heavy atom
      metals for the purpose of experimental phasing. Our results reveal that molecular
      replacement is emerging as the most successful method for phasing alpha helical
      membrane proteins, with the notable exception of the transporter family, where
      experimentally derived phase information still remains the most effective method.
      To facilitate selection of heavy atoms salts for experimental phasing an analysis
      of these was undertaken and indicates that organic mercury salts are still the
      most successful heavy atoms reagents. Interestingly the use of seleno-L
      methionine incorporated protein has increased since earlier studies into membrane
      protein phasing, so too the use of SAD and MAD as techniques for phase
      determination. Taken together this study provides a brief snapshot of phasing
      methods for alpha helical membrane proteins and suggests possible routes for
      heavy atom selection and phasing methods based on currently available data.

PMID- 23963890
TI  - Homology modeling, molecular docking and DNA binding studies of nucleotide
      excision repair UvrC protein from M. tuberculosis.
AB  - Mycobacterium tuberculosis is a Gram positive, acid-fast bacteria belonging to
      genus Mycobacterium, is the leading causative agent of most cases of
      tuberculosis. The pathogenicity of the bacteria is enhanced by its developed DNA
      repair mechanism which consists of machineries such as nucleotide excision
      repair. Nucleotide excision repair consists of excinuclease protein UvrABC
      endonuclease, multi-enzymatic complex which carries out repair of damaged DNA in
      sequential manner. UvrC protein is a part of this complex and thus helps to
      repair the damaged DNA of M. tuberculosis. Hence, structural bioinformatics study
      of UvrC protein from M. tuberculosis was carried out using homology modeling and
      molecular docking techniques. Assessment of the reliability of the homology model
      was carried out by predicting its secondary structure along with its model
      validation. The predicted structure was docked with the ATP and the interacting
      amino acid residues of UvrC protein with the ATP were found to be TRP539, PHE89,
      GLU536, ILE402 and ARG575. The binding of UvrC protein with the DNA showed two
      different domains. The residues from domain I of the protein VAL526, THR524 and
      LEU521 interact with the DNA whereas, amino acids interacting from the domain II
      of the UvrC protein included ARG597, GLU595, GLY594 and GLY592 residues. This
      predicted model could be useful to design new inhibitors of UvrC enzyme to
      prevent pathogenesis of Mycobacterium and so the tuberculosis. 

PMID- 23963891
TI  - Yeast two-hybrid analysis of PriB-interacting proteins in replication restart
      primosome: a proposed PriB-SSB interaction model.
AB  - PriB is one of the components of the replication restart primosome. The activity
      mediated by the primosomal proteins, including PriB, is required for reinitiating
      chromosomal DNA replication in bacteria after DNA damage. As such, the study of
      the interactions between PriB and members in the primosome is essential to better
      understand their mechanism of action. In this study, we investigated PriB
      interacting proteins in the primosome through the yeast two-hybrid system. Yeast
      two-hybrid analysis using two strains, Y187 and AH109, revealed that PriB
      interacts with PriA, DnaT, SSB, and itself and does not interact with DnaA, DnaB,
      DnaC, or DnaG. In addition, mutational analysis showed that PriB may bind to SSB
      via K82, K84, and K89 in the L(45) loop. Based on these preliminary data, we
      proposed a PriB-SSB interaction model. Further work can focus on determination of
      how PriB binds to the PriA-SSB complex in replication restart.

PMID- 23963892
TI  - Performance evaluation of a depth-of-interaction detector by use of position
      sensitive PMT with a super-bialkali photocathode.
AB  - Our purpose in this work was to evaluate the performance of a 4-layer depth-of
      interaction (DOI) detector composed of GSO crystals by use of a position
      sensitive photomultiplier tube (PMT) with a super-bialkali photocathode (SBA) by
      comparing it with a standard bialkali photocathode (BA) regarding the ability to
      identify the scintillating crystals, energy resolution, and timing resolution.
      The 4-layer DOI detector was composed of a 16 * 16 array of 2.9 * 2.9 * 7.5 mm(3)
      GSO crystals for each layer and an 8 * 8 multi-anode array type position
      sensitive PMT. The DOI was achieved by a reflector control method, and the Anger
      method was used for calculating interacting points. The energy resolution in full
      width at half-maximum (FWHM) at 511 keV energy for the top layer (the farthest
      from the PMT) was improved and was 12.0% for the SBA compared with the energy
      resolution of 12.7% for the BA. As indicators of crystal identification ability,
      the peak-to-valley ratio and distance-to-width ratio were calculated; the latter
      was defined as the average of the distance between peaks per the average of the
      peak width. For both metrics, improvement of several percent was obtained; for
      example, the peak-to-valley ratio was increased from 1.78 (BA) to 1.86 (SBA), and
      the distance-to-width ratio was increased from 1.47 (BA) to 1.57 (SBA). The
      timing resolution (FWHM) in the bottom layer was improved slightly and was 2.4 ns
      (SBA) compared with 2.5 ns (BA). Better performance of the DOI detector is
      expected by use of a super bialkali photocathode.

PMID- 23963893
TI  - Identification of regioisomers and enantiomers of triacylglycerols in different
      yeasts using reversed- and chiral-phase LC-MS.
AB  - LC with atmospheric pressure chemical ionization (ACPI) MS with RP and chiral
      phase was used for separation of triacylglycerols (TAGs) from yeasts of the
      genera Candida, Kluyveromyces, Rhodotorula, Saccharomyces, Torulospora,
      Trichosporon, and Yarrowia. Chiral LC-APCI-MS is based on using two columns in
      series packed with a 3,5-dimethylphenyl carbamate modified beta-cyclodextrin
      chiral phase. All regioisomers and enantiomers of TAGs containing one to five
      double bonds were separated. Molecular species of TAGs, i.e. regioisomers and
      enantiomers, were identified and quantified by MS/MS. Among the 94 identified
      TAGs, the most abundant were triolein, oleopalmitoleoolein, and
      dipalmitoleoolein. In strains producing palmitoleic acid in amounts >25% of total
      fatty acids (FAs), this acid, or unsaturated FA is bound in sn-1. In strains
      containing palmitoleic acid at 10-25% total FAs this acid is mainly bound in sn
      3, saturated FA being bound in sn-1. Strains containing <10% palmitoleic acid
      form preferentially symmetrical TAGs. 

PMID- 23963894
TI  - Long-lasting improvements in liver fat and metabolism despite body weight regain
      after dietary weight loss.
AB  - OBJECTIVE: Weight loss reduces abdominal and intrahepatic fat, thereby improving
      metabolic and cardiovascular risk. Yet, many patients regain weight after
      successful diet-induced weight loss. Long-term changes in abdominal and liver
      fat, along with liver test results and insulin resistance, are not known.
      RESEARCH DESIGN AND METHODS: We analyzed 50 overweight to obese subjects (46 +/-
      9 years of age; BMI, 32.5 +/- 3.3 kg/m2; women, 77%) who had participated in a 6
      month hypocaloric diet and were randomized to either reduced carbohydrates or
      reduced fat content. Before, directly after diet, and at an average of 24 (range,
      17-36) months follow-up, we assessed body fat distribution by magnetic resonance
      imaging and markers of liver function and insulin resistance. RESULTS: Body
      weight decreased with diet but had increased again at follow-up. Subjects also
      partially regained abdominal subcutaneous and visceral adipose tissue. In
      contrast, intrahepatic fat decreased with diet and remained reduced at follow-up
      (7.8 +/- 9.8% [baseline], 4.5 +/- 5.9% [6 months], and 4.7 +/- 5.9% [follow-up]).
      Similar patterns were observed for markers of liver function, whole-body insulin
      sensitivity, and hepatic insulin resistance. Changes in intrahepatic fat und
      intrahepatic function were independent of macronutrient composition during
      intervention and were most effective in subjects with nonalcoholic fatty liver
      disease at baseline. CONCLUSIONS: A 6-month hypocaloric diet induced improvements
      in hepatic fat, liver test results, and insulin resistance despite regaining of
      weight up to 2 years after the active intervention. Body weight and adiposity
      measurements may underestimate beneficial long-term effects of dietary
      interventions.

PMID- 23963895
TI  - Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2
      diabetes: a 24-week, randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To investigate the efficacy and tolerability of empagliflozin as add
      on to metformin and sulfonylurea in patients with type 2 diabetes. RESEARCH
      DESIGN AND METHODS: Patients inadequately controlled on metformin and
      sulfonylurea (HbA1c >=7 to <=10%) were randomized and treated with once-daily
      empagliflozin 10 mg (n = 225), empagliflozin 25 mg (n = 216), or placebo (n =
      225) for 24 weeks. The primary end point was change from baseline in HbA1c at
      week 24. Key secondary end points were changes from baseline in weight and mean
      daily glucose (MDG) at week 24. RESULTS: At week 24, adjusted mean (SE) changes
      from baseline in HbA1c were -0.17% (0.05) for placebo vs. -0.82% (0.05) and 
      0.77% (0.05) for empagliflozin 10 and 25 mg, respectively (both P < 0.001).
      Empagliflozin significantly reduced MDG, weight, and systolic (but not diastolic)
      blood pressure versus placebo. Adverse events were reported in 62.7, 67.9, and
      64.1% of patients on placebo and empagliflozin 10 and 25 mg, respectively. Events
      consistent with urinary tract infection were reported in 8.0, 10.3, and 8.3% of
      patients on placebo and empagliflozin 10 and 25 mg, respectively (females: 13.3,
      18.0, and 17.5%, respectively; males: 2.7, 2.7, and 0%, respectively). Events
      consistent with genital infection were reported in 0.9, 2.7, and 2.3% of patients
      on placebo and empagliflozin 10 and 25 mg, respectively (females: 0.9, 4.5, and
      3.9%, respectively; males: 0.9% in each group). CONCLUSIONS: Empagliflozin 10 and
      25 mg for 24 weeks as add-on to metformin plus sulfonylurea improved glycemic
      control, weight, and systolic blood pressure and were well tolerated.

PMID- 23963896
TI  - Disturbed eating behavior and omission of insulin in adolescents receiving
      intensified insulin treatment: a nationwide population-based study.
AB  - OBJECTIVE: To establish the prevalence of disturbed eating behavior (DEB) and
      insulin omission among adolescents with type 1 diabetes using intensive insulin
      treatment in a nationwide population-based study. RESEARCH DESIGN AND METHODS:
      The Diabetes Eating Problem Survey-Revised (DEPS-R) is a diabetes-specific
      screening tool for DEB. Clinical data and HbA1c were obtained from the Norwegian
      Childhood Diabetes Registry. RESULTS: A total of 770 children and adolescents 11
      19 years of age with type 1 diabetes completed the DEPS-R. A total of 27.7% of
      the females and 8.6% of the males scored above the DEPS-R cutoff. Participants
      scoring above the cutoff had significantly higher HbA1c (9.2% [77 mmol/mol]; SD,
      1.6) than participants scoring below the cutoff (8.4% [68 mmol/mol]; SD, 1.3; P <
      0.001). The prevalence of DEB increased significantly with age and weight, from
      7.2% in the underweight group to 32.7% in the obese group, and from 8.1% in the
      youngest age-group (11-13 years) to 38.1% in the oldest age-group (17-19 years).
      A total of 31.6% of the participants reported insulin restriction and 6.9%
      reported insulin omission after overeating. Patients reporting insulin
      restriction had significantly higher HbA1c (9.0% [75 mmol/mol]; SD, 1.7) than
      nonrestrictors (8.3% [67 mmol/mol]; SD, 1.2; P < 0.001). CONCLUSIONS: One-fourth
      of girls with type 1 diabetes scored above the cutoff for DEB and one-third
      reported skipping their insulin dose entirely at least occasionally after
      overeating. Both DEB and insulin restriction were associated with poorer
      metabolic control, which may increase the risk of serious late diabetes
      complications.

PMID- 23963897
TI  - Solvent-free directed patterning of a highly ordered liquid crystalline organic
      semiconductor via template-assisted self-assembly for organic transistors.
AB  - Highly ordered organic semiconductor micropatterns of the liquid-crystalline
      small molecule 2,7-didecylbenzothienobenzothiophene (C10 -BTBT) are fabricated
      using a simple method based on template-assisted self-assembly (TASA). The liquid
      crystallinity of C10 -BTBT allows solvent-free fabrication of high-performance
      printed organic field-effect transistors (OFETs). 

PMID- 23963899
TI  - Bryophytes: liverworts, mosses, and hornworts: extraction and isolation
      procedures.
AB  - There are more than 20,000 species of bryophytes in the world. Among them, almost
      of liverworts (Marchantiophyta) possess beautiful blue, yellow colored or
      colorless cellular oil bodies from which over several hundred new terpenoids,
      acetogenins, and aromatic compounds including flavonoids with more than 40 new
      carbon skeletons have been isolated. Some of the isolated compounds from
      liverworts show antimicrobial, antifungal, antiviral, allergenic contact
      dermatitis, cytotoxicity, insect antifeedant and mortality, antioxidant, nitric
      oxide (NO) production and plant growth inhibitory, neurotrophic and piscicidal
      activity, tublin polymerization inhibitory, muscle relaxing, and liver X-receptor
      (LXR)alpha agonist and (LXR)beta antagonist activities, among others. The bio-
      and chemical diversity, chemical analysis of bryophytes including extraction,
      distillation, purification, TLC, GC and GC-MS, and HPLC analysis of oil bodies of
      liverworts are surveyed.

PMID- 23963898
TI  - Immunohistochemical distribution of cell cycle proteins p27, p57, cyclin D3, PCNA
      and Ki67 in normal and diabetic human placentas.
AB  - The placenta is a regulator organ for many metabolic activities between mother
      and fetus. Therefore, fetal growth is directly related to the placental
      development. Placental development is a series of events that depend on the
      coordinated action of trophoblasts' proliferation, differentiation and invasion.
      Studies on cell cycle related proteins which control these events are fairly
      limited. How placental tissue proliferation is affected by diabetes is not
      exactly known yet. Therefore in this study, the immunohistochemical localizations
      of cell cycle related proteins like PCNA, Ki67, cyclin D3, p27 and p57 in the
      differentiation, proliferation and apoptosis mechanisms of normal and diabetic
      placentas were investigated. Information on cell cycle related proteins that
      control these events is limited and how they are affected in diabetes mellitus is
      not fully understood yet. Therefore, in this study, to understand the role of
      cell cycle regulators in diabetic placentas we aimed to determine the spatio
      temporal immunolocalizations of cell cycle regulators in diabetic and normal
      human term placentas. Term placentas were obtained from diabetic women and from
      normal pregnancies with informed consent following caesarean deliveries.
      Placental samples were stained via immunohistochemistry with PCNA, Ki67, cyclin
      D3, p27 and p57 antibodies and were examined by light microscopy. When compared
      to control placentas, PCNA, Ki67 and cyclin D3 staining intensities significantly
      increased in villous parts of diabetes group. Moreover, Ki67 and cyclin D3
      stainings also significantly increased in basal plates and chorionic plate
      respectively. In chorionic plates, p27 and p57 staining intensities significantly
      decreased in diabetic group. p57 staining also significantly decreased in villous
      parts of diabetic placentas. Placental abnormalities seen in diabetic placentas
      could be associated with proliferation and cell cycle arrest mechanisms'
      alterations occurred in diabetes mellitus. 

PMID- 23963900
TI  - Plant tissue extraction for metabolomics.
AB  - Plants are not only important producers of foods and energy storages (e.g.,
      sugars, carbohydrates, proteins, and fats) in the form of grains, fruits, and
      vegetables, they also provide many valuable products to human existence including
      wood, fibers, oils, resins, pigments, antioxidants, and sources of medicine. Most
      importantly in light of this book, plants have been a source of therapeutic and
      health promoting compounds throughout history. This chapter describes several
      essential considerations for the extraction process when aiming to study plant
      metabolism or to characterize the chemical composition of plant originated
      samples using metabolomics technologies. 

PMID- 23963901
TI  - Detection of polar metabolites through the use of gas chromatography-mass
      spectrometry.
AB  - Gas chromatography-mass spectrometry (GC-MS) is a highly reproducible and
      sensitive analytical technique that has had significant use in the area of
      metabolite profiling. GC-MS is able to detect a wide variety of metabolites, with
      highly differing chemistries. In general, extracted biological samples are
      volatilized prior to separation on a capillary column with a stationary phase
      suited to the analysis of the compounds of interest. Separated compounds are
      eluted into a mass spectrometer equipped with an electron impact ionization
      source, thereby generating a quantifiable mass spectral fingerprint. This chapter
      describes a method for the trimethylsilyl derivatization of polar metabolites,
      followed by detection and relative quantification using a gas chromatograph
      coupled to a single quadrupole mass spectrometer. Using this method will enable
      the profiling of the greatest range of polar metabolites.

PMID- 23963902
TI  - A robust GC-MS method for the quantitation of fatty acids in biological systems.
AB  - Fatty acids (FAs) are involved in a wide range of functions in biological
      systems. It is important to measure the exact amount of fatty acids in biological
      matrices in order to determine the level of fatty acids and understand the role
      they play. The ability to quantify fatty acids in various systems, especially
      plant species and microbes has recently paved the way to the mass production of
      pharmaceuticals and energy substitutes including biodiesel. This chapter
      describes an efficient method to quantify the total fatty acids (TFAs) in
      biological systems using gas chromatography-mass spectrometry (GC-MS) and a
      commercially available standard mix of fatty acid methyl esters (FAMEs) using a
      step-by-step methodology to setup a quantitation method using the Agilent
      Chemstation software.

PMID- 23963903
TI  - A workflow from untargeted LC-MS profiling to targeted natural product isolation.
AB  - Liquid chromatography-mass spectrometry (LC-MS or HPLC-MS) is an extremely
      sensitive analytical technique that enables the detection of metabolites with a
      vast range of chemistries and molecular masses. Extracts from any biological
      starting material are first fractionated chromatographically on a stationary
      phase suitable for the retention of the target molecules. The eluent is then
      transferred directly to the ionization source for MS detection. There is a vast
      range of chromatographic separation methods and MS configurations. This chapter
      describes a method for the detection of a broad range of metabolites using
      reversed phase (C18) LC-MS as well as a method for the isolation of targeted
      metabolites of interest.

PMID- 23963904
TI  - Lipidomics: extraction protocols for biological matrices.
AB  - Lipidomics is defined as a comprehensive analysis of all lipids in a biological
      system (lipidome). Lipid profiling is a fast-growing area of research due to the
      involvements of lipids incorporated with human diseases such as obesity,
      Alzheimer's diseases, and diabetes as well as in drug discovery. Recently
      improved liquid chromatography and mass spectrometric techniques has provided the
      rapid expansion of lipidomics research. Lipid extraction and sample preparation
      is an important step in lipidomics and this chapter describes lipid extractions
      from different types of samples such as plasma, tissues, yeast, and cells.

PMID- 23963905
TI  - Metabolite analysis of biological fluids and tissues by proton nuclear magnetic
      resonance spectroscopy.
AB  - NMR-based biochemical profiling of natural products has become popular due to the
      development of high-resolution instruments (>400 MHz) and cryogenically cooled
      probes/preamplifiers, by increasing the sensitivity of NMR instruments several
      fold and reducing instrument noise levels. NMR provides a rapid, nondestructive,
      high-throughput method that requires minimal sample preparation, therefore
      maintaining the biological integrity of the sample. One-dimensional (1D) solution
      state (1)H NMR is used in untargeted sample screening (metabolomics/metabonomics)
      to gain insight into spectral pattern changes associated with samples of
      different origins. Metabolomics and metabonomics contextually explains the
      systematic and quantitative measurement of metabolites that are produced from the
      biochemical reactions of living systems. This chapter describes some commonly
      used (1)H NMR experiments for identification and quantification of small
      molecular weight, water soluble metabolites in biological samples, some
      considerations for choosing the correct NMR experiment, and sample preparation
      protocols for isolating metabolites from a number of biological sample types.

PMID- 23963906
TI  - NMR spectroscopy: structure elucidation of cycloelatanene A: a natural product
      case study.
AB  - The structure elucidation of new secondary metabolites derived from marine and
      terrestrial sources is frequently a challenging task. The hurdles include the
      ability to isolate stable secondary metabolites of sufficient purity that are
      often present in <0.5 % of the dry weight of the sample. This usually involves a
      minimum of several chromatographic purification steps. The second issue is the
      stability of the compound isolated. It must always be assumed when dealing with
      the isolation of natural products that the compound may rapidly degrade during
      and/or after the isolation, due to sensitivity to light, air oxidation, and/or
      temperature. In this way, precautions need to be taken, as much as possible to
      avoid any such chemical inter-conversions and/or degradations. Immediately after
      purification, the next step is to rapidly acquire all analytical spectroscopic
      data in order to complete the characterization of the isolated secondary
      metabolite(s), prior to any possible decomposition. The final hurdle in this
      multiple step process, especially in the acquisition of the NMR spectroscopic and
      other analytical data (mass spectra, infrared and ultra-violet spectra, optical
      rotation, etc.), is to assemble the structural moieties/units in an effort to
      complete the structure elucidation. Often ambiguity with the elucidation of the
      final structure remains when structural fragments identified are difficult to
      piece together on the basis of the HMBC NMR correlations or when the relative
      configuration cannot be unequivocally identified on the basis of NOE NMR
      enhancements observed. Herein, we describe the methodology used to carry out the
      structure elucidation of a new C16 chamigrene, cycloelatanene A (5) which was
      isolated from the southern Australian marine alga Laurencia elata
      (Rhodomelaceae). The general approach and principles used in the structure
      determination of this compound can be applied to the structure elucidation of
      other small molecular weight compounds derived from either natural or synthetic
      sources.

PMID- 23963907
TI  - NMR-based metabolomics: a probe to utilize biodiversity.
AB  - Metabolomics is a comprehensive profiling tool used to identify qualitatively and
      quantitatively all the metabolites present in a biological system. As the number
      of metabolites in a living being is assumed to be around 30,000, it is necessary
      to use an adequate extraction procedure and a good analytical technique to
      perform metabolomic analyses. Each analytical platform used in metabolomics has
      both advantages and disadvantages in terms of the sensitivity and resolution for
      metabolites to be detected. Of the methods, nuclear magnetic resonance (NMR)
      spectroscopy has been proved to have several advantages over other MS-based
      methods. NMR provides an efficient, robust, and nondestructive metabolomics
      analysis of crude extracts or samples as well as easy quantitation without
      calibration curves for each metabolite, although it shows relatively low
      sensitivity than MS-based methods. Thus, NMR-based metabolomics have been often
      used for the first step to capture the insight of the metabolome of organisms.
      This chapter presents general steps of NMR-based metabolomic analysis involved in
      the study of biodiversity.

PMID- 23963908
TI  - Extraction protocol for nontargeted NMR and LC-MS metabolomics-based analysis of
      hard coral and their algal symbionts.
AB  - Metabolomics and in particular, nontargeted metabolomics, has become a popular
      technique for the study of biological samples as it provides considerable amounts
      of information on extractable metabolites and is ideal for studying the metabolic
      response of an organism to stressors in its environment. One such organism, the
      symbiotic hard coral, presents its own complexity when considering a metabolomics
      approach in that it forms intricate associations with an array of symbiotic macro
      and microbiota. While not discounting the importance of these many associations
      to the function of the coral holobiont, the coral-Symbiodinium relationship has
      been the most studied to date and as such, is the primary focus of this
      extraction protocol. This protocol provides details for the sample collection,
      extraction, and measurement of hard coral holobiont metabolites using both (1)H
      nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography coupled
      with mass spectrometry (LC-MS). Using this nontargeted metabolomics approach, the
      holobiont metabolism can be investigated for perturbations resulting from either
      (1) natural or anthropogenic environmental challenges, (2) the controlled
      application of stressors, and (3) differences between phenotypes or species.
      Consequently, this protocol will benefit both environmental and natural products
      based research of hard coral and their algal symbionts. Every effort has been
      made to provide the reader with all the details required to perform this
      protocol, including many of the costly and time consuming "pitfalls" or "traps"
      that were discovered during its development. As a result, this protocol can be
      confidently accomplished by those with less experience in the extraction and
      analysis of symbiotic hard coral, requiring minimal user input whilst ensuring
      reproducible and reliable results using readily available lab ware and reagents.

PMID- 23963909
TI  - Determination of absolute configuration using single crystal X-ray diffraction.
AB  - Single crystal X-ray crystallography is the most powerful structural method for
      the determination of the 3D structures of molecules. While the results of a
      routine diffraction experiment readily provide unambiguous determination of the
      relative configuration of all stereogenic centers in the molecule, determination
      of absolute configuration is more challenging. This chapter provides some helpful
      tips towards increasing the chances of success in the determination of the
      absolute configuration of a chiral, enantiomerically pure natural product using X
      ray crystallography. 

PMID- 23963910
TI  - Natural product chemistry in action: the synthesis of melatonin metabolites K1
      and K2.
AB  - Natural product chemistry often yields new compounds with great potential for
      economic and/or health benefits. However, most natural compounds must be
      artificially synthesized on an industrial scale to generate enough active
      ingredients to be commercially viable. Thus chemical synthesis is an essential
      tool of natural product chemistry. Chemical synthesis may be defined as the
      purposeful execution of a series of chemical reactions in order to obtain a
      product(s) of interest or to demonstrate important methodologies. Organic
      synthesis is (unsurprisingly) specifically concerned with the construction of
      organic compounds, which are often of an exceedingly high level of structural
      complexity. Each step of any form of chemical synthesis involves a chemical
      reaction, and the reagents and conditions for each of these need to be designed
      to give a good yield and a pure product. Here we illustrate this methodology
      using a simple protocol for the synthesis of the metabolites of the natural
      product melatonin, the kynurenamines N1-acetyl-N2-formyl-5-methoxykynurenine (K1)
      and N-acetyl-5-methoxykynurenamine (K2). The four key synthetic transformations
      involve (a) conversion of 4-methoxy aniline into the tert-butyl (4
      methoxyphenyl)carbamate, (b) ortho-lithiation-iodination with tert-butyllithium
      1,2-iodoethane, (c) use of the Sonogashira reaction with N-acetyl propargylamine,
      and (d) sequential alkyne hydration/formylation to give (K1) or alkyne to give
      (K2).

PMID- 23963911
TI  - Discovery, biosynthesis, and rational engineering of novel enterocin and
      wailupemycin polyketide analogues.
AB  - The marine actinomycete Streptomyces maritimus produces a structurally diverse
      set of unusual polyketide natural products including the major metabolite
      enterocin. Investigations of enterocin biosynthesis revealed that the unique
      carbon skeleton is derived from an aromatic polyketide pathway which is
      genetically coded by the 21.3 kb enc gene cluster in S. maritimus.
      Characterization of the enc biosynthesis gene cluster and subsequent manipulation
      of it via heterologous expression and/or mutagenesis enabled the discovery of
      other enc-based metabolites that were produced in only very minor amounts in the
      wild type. Also described are techniques used to harness the enterocin
      biosynthetic machinery in order to generate unnatural enc-derived polyketide
      analogues. This review focuses upon the molecular methods used in combination
      with classical natural products detection and isolation techniques to access
      minor metabolites of the S. maritimus secondary metabolome.

PMID- 23963912
TI  - Bioassays for anticancer activities.
AB  - The MTT/MTS in vitro cell proliferation assay is one of the most widely used
      assays for evaluating preliminary anticancer activity of both synthetic
      derivatives and natural products and natural product extracts. The highly
      reliable, colorimetric based assay is readily performed on a wide range of cell
      lines. This assay gives an indication of whole cell cytotoxicity; however, to
      determine the exact molecular target further assays need to be performed. Of
      these, kinase inhibition assays are also one of the most widespread enzyme
      inhibition screening assays performed. Kinases are enzymes that play a key role
      in a number of physiological processes and their inhibitors have been found to
      exhibit anticancer activity against various human cancer cell lines. Herein, we
      describe the methods for performing both in vitro MTT/MTS cytotoxicity and kinase
      enzyme inhibition assays. These are two of the most useful anticancer screening
      techniques available that are relatively economical and can be easily and
      routinely performed in the laboratory to characterize anticancer activity. Both
      assays are highly versatile and can be modified to test against targeted disease
      processes by using specific kinase enzymes or cell lines. 

PMID- 23963913
TI  - Screening for antidiabetic activities.
AB  - Screening extracts and drug entities for antidiabetic bioactivity is essentially
      limited to animal models as the processes leading to hyperglycemia and the
      complications of diabetes involve more than one organ. Further, in vitro results
      seldom translate into meaningful in vivo outcomes especially in a disease such as
      Diabetes Mellitus. In vivo studies on specialized animal models have allowed
      great progress in tailoring research questions towards individualized genetic and
      biochemical contributors and their effect on the pathogenesis of the disease
      processes. Various disease models have been used either through genetic
      manipulation (transgenic models) or through chemical induction (disease-induced
      models). Although there is a surplus of animal models (spontaneous and induced)
      to study Type I and Type II diabetes, there is no ideal or standard model for
      studying the individualized effects of various classes of antidiabetic drugs.
      Rodents, most commonly rats and mice, have been used by researchers as animal
      models of the disease and both normoglycemic and diabetic animals are used to
      assess the antidiabetic activities of drugs or extracts under investigation.
      Screening for antidiabetic activities can be achieved by measuring a wide range
      of biomarkers and end points including blood glucose and insulin levels. 

PMID- 23963914
TI  - Screening for antibacterial, antifungal, and anti quorum sensing activity.
AB  - The plate-hole diffusion assay is an invaluable screening tool to evaluate the
      antibacterial potential of natural products. It relies on the diffusion of test
      material from pre-cut wells through agar seeded with bacteria. Samples that are
      capable of inhibiting bacterial growth will produce a clear zone surrounding
      their well. For the evaluation of antifungal activity of natural products, we
      describe the broth microdilution method. This assay is performed using a 96 well
      microtiter tray containing fungal inoculum, test medium and natural product
      material. Samples demonstrating antifungal activity will prevent any discernible
      growth as detected visually. A disk diffusion assay, utilizing the pigmented
      indicator strain Chromobacterium violaceum, is described here for the screening
      of natural products for anti quorum sensing activity. Inhibition of quorum
      sensing results in growth of non-pigmented bacteria. 

PMID- 23963915
TI  - Metabolomics and dereplication strategies in natural products.
AB  - Metabolomic methods can be utilized to screen diverse biological sources of
      potentially novel and sustainable sources of antibiotics and pharmacologically
      active drugs. Dereplication studies by high resolution Fourier transform mass
      spectrometry coupled to liquid chromatography (LC-HRFTMS) and nuclear magnetic
      resonance (NMR) spectroscopy can establish the chemical profile of endophytic
      and/or endozoic microbial extracts and their plant or animal sources. Identifying
      the compounds of interest at an early stage will aid in the isolation of the
      bioactive components. Therefore metabolite profiling is important for functional
      genomics and in the search for new pharmacologically active compounds. Using the
      tools of metabolomics through the employment of LC-HRFTMS as well as high
      resolution NMR will be a very efficient approach. Metabolomic profiling has found
      its application in screening extracts of macroorganisms as well as in the
      isolation and cultivation of suspected microbial producers of bioactive natural
      products.Metabolomics is being applied to identify and biotechnologically
      optimize the production of pharmacologically active secondary metabolites. The
      links between metabolome evolution during optimization and processing factors can
      be identified through metabolomics. Information obtained from a metabolomics
      dataset can efficiently establish cultivation and production processes at a small
      scale which will be finally scaled up to a fermenter system, while maintaining or
      enhancing synthesis of the desired compounds. MZmine (BMC Bioinformatics 11:395
      399, 2010; http://mzmine.sourceforge.net/download.shtml ) and SIEVE (
      http://www.vastscientific.com/resources/index.html ; Rapid Commun Mass Spectrom
      22:1912-1918, 2008) softwares are utilized to perform differential analysis of
      sample populations to find significant expressed features of complex biomarkers
      between parameter variables. Metabolomes are identified with the aid of existing
      high resolution MS and NMR records from online or in-house databases like
      AntiMarin, a merger database of Antibase (Laatsch H. Antibase Version 4.0 - The
      Natural Compound Identifier. Wiley-VCH Verlag GmbH & Co. KGaA, 2012) for
      microbial secondary metabolites as well as higher fungi and MarinLit for marine
      natural products (Blunt J. MarinLit. University of Canterbury, New Zealand,
      2012). This is further validated through available reference standards and NMR
      experiments. Metabolomics has become a powerful tool in systems biology which
      allows us to gain insights into the potential of natural isolates for synthesis
      of significant quantities of promising new agents and allows us to manipulate the
      environment within fermentation systems in a rational manner to select a desired
      metabolome.

PMID- 23963916
TI  - Bridging the gap: basic metabolomics methods for natural product chemistry.
AB  - Natural products and their derivatives often have potent physiological activities
      and therefore play important roles as both frontline treatments for many diseases
      and as the inspiration for chemically synthesized therapeutics. However, the
      detection and synthesis of new therapeutic compounds derived from, or inspired by
      natural compounds has declined in recent years due to the increased difficulty of
      identifying and isolating novel active compounds. A new strategy is therefore
      necessary to jumpstart this field of research. Metabolomics, including both
      targeted and global metabolite profiling strategies, has the potential to be
      instrumental in this effort since it allows a systematic study of complex
      mixtures (such as plant extracts) without the need for prior isolation of active
      ingredients (or mixtures thereof). Here we describe the basic steps for
      conducting metabolomics experiments and analyzing the results using some of the
      more commonly used analytical and statistical methodologies.

PMID- 23963917
TI  - Strategies in biomarker discovery. Peak annotation by MS and targeted LC-MS micro
      fractionation for de novo structure identification by micro-NMR.
AB  - In metabolomic studies the identification of biomarkers is a key step but
      represents a serious bottleneck since the de novo identification of natural
      products is a lengthy process. A strategy for the dereplication and peak
      annotation of plant biomarkers is presented based on high resolution mass spectra
      acquired on a quadrupole-time-of-flight mass spectrometry coupled to ultra-high
      pressure liquid chromatography and chemotaxonomy information. A rational approach
      for the targeted LC-MS micro-isolation of biomarkers followed by de novo
      identification by NMR at the microgram scale is described, based on gradient
      transfer from the analytical scale and chromatographic modelling. The methodology
      is illustrated by the identification of various stress biomarkers of the plant
      wound response using Arabidopsis thaliana as a model.

PMID- 23963918
TI  - Statistical analysis of metabolomics data.
AB  - Statistical matters form an integral part of a metabolomics experiment. In this
      chapter we describe several important aspects in the analysis of metabolomics
      data such as the removal of unwanted variation and the identification of
      differentially abundant metabolites, along with a number of other essential
      statistical considerations. 

PMID- 23963919
TI  - Future development, innovation and promotion of European unique food: an
      interdisciplinary research framework perspective.
AB  - Unique food products constitute a very important element of European food
      business, culture, identity and heritage. Understanding the uniqueness of food in
      Europe from a research-based interdisciplinary perspective will be a critical
      factor in promoting the competitiveness of artisanal food industries going
      forward both locally and internationally. Success will support the
      competitiveness of the European food industry, in particular, small and medium
      enterprises, by enabling substantial product differentiation potential for
      producers and providing ample variety in food choice for the consumer. In
      addition, it will contribute to promotion of sustainable agriculture and
      development of rural areas, protecting them from depopulation. In order to meet
      the demands of a developing fundamental shift in European Union agricultural
      focus to greener, sustainable farming practices and wider rural development and
      to ensure success for local small-scale producers, this paper discusses the
      future direction of research in the field of unique European foods. The paper
      presents a perspective which promotes optimisation and innovation in unique food
      products in Europe through the integration of advanced knowledge and
      technologies. A framework is presented covering location, identity, perception
      and well-being as research areas needing synergy to bridge the research knowledge
      deficit in determination and specification of food identity in the European
      Union. The ultimate aim being promotion of sustainable agriculture and rural
      development, particularly in territories across the European Union where unique
      food is strategically and scientifically under-defined.

PMID- 23963922
TI  - Neuropathy, neuropathic pain, and sickle cell disease.

PMID- 23963921
TI  - Interaction of HMG proteins and H1 with hybrid PNA-DNA junctions.
AB  - The objective of this study was to evaluate the effects of inserting peptide
      nucleic acid (PNA) sequences into the protein-binding surface of an immobilized
      four-way junction (4WJ). Here we compare the classic immobile DNA junction, J1,
      with two PNA containing hybrid junctions (4WJ-PNA1 and 4WJ-PNA3 ). The protein
      interactions of each 4WJ were evaluated using recombinant high mobility group
      proteins from rat (HMGB1b and HMGB1b/R26A) and human histone H1. In vitro studies
      show that both HMG and H1 proteins display high binding affinity toward 4WJ's. A
      4WJ can access different conformations depending on ionic environment, most
      simply interpreted by a two-state equilibrium between: (i) an open-x state
      favored by absence of Mg(2+), low salt, and protein binding, and (ii) a compact
      stacked-x state favored by Mg(2+). 4WJ-PNA3, like J1, shifts readily from an open
      to stacked conformation in the presence of Mg(+2), while 4WJ-PNA1 does not.
      Circular dichroism spectra indicate that HMGB1b recognizes each of the hybrid
      junctions. H1, however, displays a strong preference for J1 relative to the
      hybrids. More extensive binding analysis revealed that HMGB1b binds J1 and 4WJ
      PNA3 with nearly identical affinity (K(D)s) and 4WJ-PNA1 with two-fold lower
      affinity. Thus both the sequence/location of the PNA sequence and the protein
      determine the structural and protein recognition properties of 4WJs.

PMID- 23963924
TI  - Method to predict gas chromatographic response factors for the trace-level
      analysis of volatile organic compounds based on the effective carbon number
      concept.
AB  - A procedure has been developed to estimate GC-MS response factors based on the
      theory of effective carbon number defined as the sum of the carbon number and
      carbon number equivalent for each selected molecular descriptor (multiplied by
      its number of occurrences) in each compound's molecular structure. As a means to
      validate the effective carbon number procedure for GC-MS analysis, a test suite
      of 19 volatile organic compounds was analyzed by the sorbent-tube thermal
      desorption method. In the effective carbon number procedure, the carbon number
      equivalent for each descriptor was determined to yield the optimal linear plots
      between response factor versus the effective carbon number with the maximum R(2)
      (>0.975) and the minimum mean absolute error (<5%). Effective carbon number
      analysis is validated as a potent approach to estimate response factor values for
      most compounds amenable to the sorbent-tube thermal desorption GC-MS method.
      Overall, it is concluded that the application of response factor versus effective
      carbon number relationship can produce fairly reliable prediction with reduced
      errors relative to other comparable procedures such as the response factor versus
      the carbon number approach. 

PMID- 23963923
TI  - Bidirectional immunomodulatory activities of polysaccharides purified from
      Pleurotus nebrodensis.
AB  - A novel Pleurotus nebrodensis polysaccharide (PN50G) was purified, characterized,
      and cultured with RAW264.7 macrophages to evaluate its bidirectional
      immunostimulating characteristics. PN50G was purified by using Sepharose 4B gel
      filtration; the molecular weight of PN50G was distributed at 2,000 kDa. The total
      protein and carbohydrate constituent ratios in PN50G were 2.6 +/- 0.9 % and 92.4
      +/- 6.1 % (w/w), respectively, which suggests that PN50G may be a major proteo
      polysaccharide component. The phagocytosis of macrophages was improved
      significantly, and remarkable changes were observed in the morphology of PN50G
      treated cells. Compared with the control group, the productions of tumor necrosis
      factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-10 (IL-10), and
      inducible nitric oxide synthase (iNOS) in the macrophages as well as the
      messenger RNA expressions were strongly induced by PN50G. Pro-/anti-inflammatory
      (IL-6/IL-10, TNF-alpha/IL-10, NO/IL-10) cytokine secretion ratios by
      lipopolysaccharide-stimulated RAW264.7 macrophages were significantly decreased
      by PN50G treatments in a dose-dependent manner under an excessive immune
      experimental model. This study suggests that purified PN50G can improve immunity
      and suppress immune overactivity in LPS-induced macrophages in a preventive
      manner to coordinate innate immunity and inflammatory responses.

PMID- 23963925
TI  - Pleural recurrence after surgery for pleomorphic adenoma arising from peripheral
      lung: computed tomography-guided percutaneous needle biopsy as a possible
      mechanism of local failure.
AB  - A 75-year-old male was referred to our hospital because of an abnormal shadow
      found in the right lung 2 years prior that had been increasing in size. Chest
      computed tomography showed a 1-cm well-defined nodule in the periphery of the
      right middle lobe. Although a computed tomography-guided percutaneous needle
      biopsy was performed, the results were indeterminate. In observations over the
      course of 1 year, the tumor size increased. Surgical resection was finally
      performed for diagnosis and treatment, and histological findings revealed a
      pulmonary pleomorphic adenoma. 2 years after surgery, pleural dissemination
      unfortunately developed. We present here a case of recurrence as pleural
      dissemination despite complete resection of a pulmonary pleomorphic adenoma
      arising from peripheral lung tissue. There is a possibility that the local
      failure is related to percutaneous needle biopsy.

PMID- 23963926
TI  - Direct-write thermocapillary dewetting of polymer thin films by a laser-induced
      thermal gradient.
AB  - A positive-tone 2D direct-write technique that can achieve sub-wavelength
      patterning by non-linear overlap effects in a conventional polymer system is
      described. The technique involves relatively inexpensive free-space optics, skips
      the usual development step, and promises the possibility of a lithographic method
      that is solvent-free.

PMID- 23963928
TI  - Introduction to the immune system.
AB  - The immune system in a broad sense is a mechanism that allows a living organism
      to discriminate between "self" and "non-self." Examples of immune systems occur
      in multicellular organisms as simple and ancient as sea sponges. In fact, complex
      multicellular life would be impossible without the ability to exclude external
      life from the internal environment. This introduction to the immune system
      explores the cell types and soluble factors involved in immune reactions, as well
      as their location in the body during development and maintenance. Additionally, a
      description of the immunological events during an innate and adaptive immune
      reaction to an infection is discussed, as well as a brief introduction to
      autoimmunity and cancer immunity. 

PMID- 23963927
TI  - BAP1 protein is a progression factor in malignant pleural mesothelioma.
AB  - Human malignant pleural mesothelioma (MPM) is an aggressive cancer due to former
      asbestos exposure with little knowledge about prognostic factors of outcome and
      resistance to conventional therapy. BRCA1-associated protein 1 (BAP1) is a tumor
      suppressor gene that is frequently lost in MPM. Germline mutations of BAP1
      predispose to several different tumors including malignant mesothelioma. Our
      study aimed to clarify if asbestos exposure has an influence on BAP1 expression
      and if BAP1 expression could be used as a prognostic factor of outcome. An
      immunohistochemical staining for BAP1 was performed on 123 MPM tissue samples and
      the expression levels have been correlated with asbestos exposure and overall
      survival time. BAP1 expression was not associated with asbestos exposure but we
      detected a significant effect of BAP1 expression on overall survival time--the
      higher the BAP1 expression (non-mutated BAP1), the shorter the overall survival.
      BAP1 mutation has been linked to non-asbestos induced familial mesotheliomas,
      which usually belong to the long survivor group and BAP1 is most probably
      functioning differently than in sporadic cases. Further investigations need to be
      performed to characterize the BAP1 mutations and to identify the BAP1 downstream
      targets in MPM.

PMID- 23963929
TI  - Immunoproteomics: current technology and applications.
AB  - The varied landscape of the adaptive immune response is determined by the
      peptides presented by immune cells, derived from viral or microbial pathogens or
      cancerous cells. The study of immune biomarkers or antigens is not new and
      classical methods such as agglutination, enzyme-linked immunosorbent assay, or
      Western blotting have been used for many years to study the immune response to
      vaccination or disease. However, in many of these traditional techniques, protein
      or peptide identification has often been the bottleneck. Recent advances in
      genomics and proteomics, has led to many of the rapid advances in proteomics
      approaches. Immunoproteomics describes a rapidly growing collection of approaches
      that have the common goal of identifying and measuring antigenic peptides or
      proteins. This includes gel based, array based, mass spectrometry, DNA based, or
      in silico approaches. Immunoproteomics is yielding an understanding of disease
      and disease progression, vaccine candidates, and biomarkers. This review gives an
      overview of immunoproteomics and closely related technologies that are used to
      define the full set of antigens targeted by the immune system during disease. 

PMID- 23963930
TI  - Antigen identification using SEREX.
AB  - Serological analysis of recombinant cDNA expression libraries (SEREX) allows
      systematic identification of antigens recognized by the spontaneous autoantibody
      repertoire of patients with cancer and autoimmune disease. SEREX is based on
      screening of lambda phage expression libraries constructed from diseased tissue
      with the autologous patient's serum. This chapter provides the key protocols for
      SEREX immunoscreening and for downstream validation of autoantigens. 

PMID- 23963931
TI  - Antigen discovery using whole-genome phage display libraries.
AB  - In the last two decades phage display technology has been used for investigating
      complex biological processes and isolating molecules of practical value in
      several applications. Bacteriophage lambda, representing a classical cloning and
      expression system, has also been exploited for generating display libraries of
      small peptides and protein domains. More recently, large cDNA and whole-genome
      lambda-display libraries of human pathogens have been generated for the discovery
      of new antigens for biomedical applications. Here, we describe the construction
      of a whole-genome library of a common pathogen-Streptococcus pneumoniae-and the
      use of this library for the molecular dissection of the human B-cell response
      against bacterial infection and colonization. 

PMID- 23963932
TI  - Methods and applications of serological proteome analysis.
AB  - The study of the humoral response to infectious diseases and chronic diseases,
      such as cancer, is important for many reasons, including understanding the host
      response to disease, identification of protective antigens, vaccine development,
      and discovery of biomarkers for early diagnosis. During the past decade,
      proteomic approaches, such as serological proteome analysis (SERPA), have been
      used to identify the repertoire of immunoreactive proteins in various diseases.
      In this chapter, we provide an outline of the SERPA approach, using the analysis
      of sera from mice vaccinated with a live attenuated tularemia vaccine as an
      example. 

PMID- 23963933
TI  - Pre-absorbed immunoproteomics: a novel method for the detection of bacterial
      surface proteins.
AB  - Bacterial surface proteins are often investigated as potential vaccine candidates
      and biomarkers of virulence. In this chapter, a novel method for identifying
      bacterial surface proteins is presented, which combines immunoproteomic with
      immunoserologic techniques. Immunoproteomics, involving the separation of
      proteins by two-dimensional electrophoresis (2-DE) and Western blotting, has
      become an increasingly popular method for identifying immunoreactive proteins. In
      conventional serological technique, cross-absorption is a powerful method used to
      minimize cross reaction during agglutination assays. The serum pre-absorption
      process in our method was developed from cross-absorption but modified to remove
      antibodies that recognized bacterial surface antigens, thereby generating pre
      absorbed sera. These pre-absorbed sera were used in Western blotting after 2-DE
      to find bacterial surface protein antigens. This new method has been proven to be
      a useful tool for identifying surface proteins, and aid in the development of new
      vaccine subunits and disease diagnostics. 

PMID- 23963934
TI  - Identification of the antigen content of electroimmunoprecipitates.
AB  - Polyclonal antibodies including purified antibody fractions and animal or human
      antisera may react with unknown antigens or antigens other than their main
      specificity in reactions that are best visualized by gel
      electroimmunoprecipitation methods, e.g., when analyzing complex antigen
      mixtures. The great advantage of gel immunoprecipitation approaches is that each
      immunoprecipitate contains antigen in a pure form and that the precipitate is
      separated by position, shape, and size from other precipitates in the complex
      patterns of crossed immunoelectrophoresis. The identification of the antigen
      content of such immunoprecipitates is important but challenging because of the
      very stable, high affinity complex formation leading to precipitation in the
      gels. Here, we present detailed step-by-step recipes for identifying the antigen
      content of electroimmunoprecipitates. 

PMID- 23963935
TI  - An immunoproteomics approach to screen the antigenicity of the influenza virus.
AB  - The structure and antigenicity of protein antigens of the influenza virus are
      screened in a single step employing an immunoproteomics approach. Matrix-assisted
      laser desorption ionization mass spectrometry (MALDI-MS) coupled to gel
      electrophoresis is used both to identify viral antigens and screen their
      antigenicity. Earlier evidence that antigen-antibody complexes can survive on
      MALDI targets has allowed both the primary structure and antigenicity of viral
      strains to be rapidly screened with the specific localization of protein
      epitopes. The approach is anticipated to have a greater role in the future
      surveillance of the virus and should also aid in the development of immunogenic
      peptide constructs as alternatives to whole virus for vaccination. 

PMID- 23963936
TI  - In Vivo Microbial Antigen Discovery (InMAD) to identify diagnostic proteins and
      polysaccharides that are circulating during microbial infections.
AB  - Immunoassays employed at the point-of-care (POC) are often useful for diagnosing
      acute infections. Many of these assays rely on identification of microbial
      antigens that are secreted or shed during infection. However, determining which
      microbial antigens are best to target by immunoassay can be the most difficult
      aspect of developing a new diagnostic product. Here we describe a novel technique
      termed "In vivo Microbial Antigen Discovery" or "InMAD" for identification of
      microbial antigens that may be targeted for the diagnosis of infectious diseases.

PMID- 23963937
TI  - Chemo-enzymatic production of O-glycopeptides for the detection of serum
      glycopeptide antibodies.
AB  - Protein microarray is a highly sensitive tool for antibody detection in serum.
      Monitoring of patients' antibody titers to specific antigens is increasingly
      employed in the diagnosis of several conditions, ranging from infectious
      diseases, allergies, autoimmune diseases, and cancer. In this protocol we present
      a detailed method for enzymatic generation of disease-specific O-glycopeptides
      and how to monitor the antibody response to these in serum using microarray
      technology. 

PMID- 23963938
TI  - Enrichment and characterization of glycopeptide epitopes from complex mixtures.
AB  - Antigen posttranslational modifications, including glycosylation, are recognized
      by the innate and adaptive arms of the immune system. Analytical approaches,
      including mass spectrometry and allied techniques, have allowed advances in the
      enrichment and identification of glyco-antigens, particularly T-cell epitopes.
      Similarly, major advances have been made in the identification, isolation, and
      detailed characterization of prokaryotic and eukaryotic glycoproteins and
      glycopeptides. In particular, peptide centric approaches are now capable of
      enriching low level glycopeptides from highly complex peptide mixtures.
      Similarly, advanced mass spectrometry methods allow identification of
      glycopeptides, characterization of glycans, and mapping of modification sites.
      Herein, we describe methods developed in our laboratory for the broad study of
      glycopeptides and illustrate how these approaches can be exploited to further our
      understanding of the identity and nature of glycopeptide epitopes in various
      diseases or auto immune disorders. 

PMID- 23963939
TI  - Whole-cell MALDI-TOF mass spectrometry: a tool for immune cell analysis and
      characterization.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) is widely used in proteomics. It has been recently demonstrated
      that MALDI-TOF MS can be used to identify and classify numerous bacterial species
      or subspecies. We applied MALDI-TOF MS directly to intact mammalian cells, and we
      found that this method is valuable to identify human circulating cells and cells
      involved in the immune response including macrophages. As macrophages are
      characterized by a high degree of plasticity in response to their
      microenvironment, we stimulated human macrophages with cytokines, bacterial
      products, and a variety of bacteria. We found that MALDI-TOF MS discriminated
      unstimulated and stimulated macrophages, and also detected multifaceted
      activation of macrophages. We conclude that whole-cell MALDI-TOF MS is an
      accurate method to identify various cell types and to detect subtle modifications
      in cell activity. 

PMID- 23963940
TI  - Cell-based arrays for the identification of interacting polypeptide domains or
      epitopes.
AB  - The specific regions on proteins which are responsible for protein-protein
      interaction are called interacting domains, or epitopes in case of antigen
      antibody binding. These domains are one feature to characterize proteins and are
      important in clinical diagnostics and research. For the mapping of such domains
      the use of protein/peptide arrays has become popular. Regardless of which kind of
      array, the major requirements are a high number of candidates arranged in the
      array, high quality, ease of use, and cost-effectiveness. Here, the authors
      describe a general protocol for mapping the interacting domains of proteins
      demonstrated by a high affinity protein interaction, the interaction of an
      antibody to an antigen. The chapter describes a stepwise protocol from library
      production to the verification of the domain by the use of an automated cell
      based polypeptide array, which comprises the named requirements of a good array. 

PMID- 23963941
TI  - Identification and quantitation of MHC class II-bound peptides from mouse spleen
      dendritic cells by immunoprecipitation and mass spectrometry analysis.
AB  - Advances in immunology and immune therapies require knowledge of antigenic
      peptide sequences that are presented on MHC class II and class I molecules of
      antigen presenting cells. The most specialized antigen presenting cells are
      dendritic cells (DCs). In the past, the small number of DCs that could be
      isolated from mouse spleen prevented direct analysis of the MHC II peptide
      repertoire presented by DCs. Here we describe a protocol that integrates
      immunological methods (in vivo enrichment of mouse spleen DCs by Flt3L treatment
      and immunoprecipitation of MHC II-peptide complexes), mass spectrometry analysis
      and peptide synthesis (LC-MS/MS and quantitation analysis for non tryptic
      peptides) to identify and quantitate the endogenous peptides that are bound to
      MHC II molecules on DCs. The described method produces quantitative data that are
      reproducible and reliable enough to cover a wide range of peptide copy numbers.
      We propose the application of this method in future studies to quantitatively
      investigate the MHC II repertoire on DCs presented during viral infections or
      different immunizations in vaccine development research. 

PMID- 23963942
TI  - Construction and screening of an antigen-derived peptide library displayed on
      yeast cell surface for CD4+ T cell epitope identification.
AB  - Identification of T cell epitopes is a critical, but often difficult step in
      studying T cell function and developing peptide-based vaccines and
      immunotherapies. Unlike antibodies that recognize free soluble antigens, T cell
      receptor (TCR) recognizes its epitope bound to major histocompatibility complex
      (MHC) expressed on antigen presenting cells (APCs). In addition, the examination
      of T cell epitope activity requires the use of professional APCs, which are
      difficult to isolate, expand, and maintain. To address these issues, we have
      developed a facile, accurate, and high-throughput method for T cell epitope
      mapping by screening antigen-derived peptide libraries in complex with MHC
      protein displayed on yeast cell surface. Here, we use hemagglutinin and influenza
      A virus X31/A/Aichi/68 as examples to describe the key steps in identification of
      CD4+ T cell epitopes from a single antigenic protein and the entire genome of a
      pathogen, respectively. Methods for single-chain peptide-MHC complex vector
      design, yeast surface display, peptide library generation in Escherichia coli,
      and functional screening in Saccharomyces cerevisiae are discussed. 

PMID- 23963943
TI  - Profiling of cytokine and chemokine responses using multiplex bead array
      technology.
AB  - Multiplex bead array technology expands upon the principles of the enzyme-linked
      immunosorbent assay by allowing the simultaneous quantification of a large number
      of cytokines and chemokines within a single sample. This allows for the
      researcher more freedom to investigate complex immune responses both in vivo and
      in vitro. Here we describe the detailed assay protocol and technical tips for
      simultaneous quantification of multiple cytokines and chemokines in mouse
      biological fluids such as sera, bronchoalveolar lavage fluid, tissue homogenate
      supernatant, and tissue culture supernatant, using a multiplex bead array assay. 

PMID- 23963944
TI  - Preparation of the low molecular weight serum proteome for mass spectrometry
      analysis.
AB  - The discovery of viable biomarkers or indicators of disease states is complicated
      by the inherent complexity of the chosen biological specimen. Every sample,
      whether it is serum, plasma, urine, tissue, cells, or a host of others, contains
      thousands of large and small components, each interacting in multiple ways. The
      need to concentrate on a group of these components to narrow the focus on a
      potential biomarker candidate becomes, out of necessity, a priority, especially
      in the search for immune-related low molecular weight serum biomarkers. One such
      method in the field of proteomics is to divide the sample proteome into groups
      based on the size of the protein, analyze each group, and mine the data for
      statistically significant items. This chapter details a portion of this method,
      concentrating on a method for fractionating and analyzing the low molecular
      weight proteome of human serum. 

PMID- 23963945
TI  - Identification of protein biomarkers in human serum using iTRAQ and shotgun mass
      spectrometry.
AB  - Blood serum is one of the easiest accessible sources of biomarkers and its
      proteome presents a significant parcel of immune system proteins. These proteins
      can provide not only biological explanation but also diagnostic and drug response
      answers independently of the type of disease or condition in question. Shotgun
      mass spectrometry has profoundly contributed to proteome analysis and is
      presently considered as an indispensible tool in the field of biomarker
      discovery. In addition, the multiplexing potential of isotopic labeling
      techniques such as iTRAQ can increase statistical relevance and accuracy of
      proteomic data through the simultaneous analysis of different biological samples.
      Here, we describe a complete protocol using iTRAQ in a shotgun proteomics
      workflow along with data analysis steps, customized for the challenges associated
      with the serum proteome. 

PMID- 23963946
TI  - Genome-based bioinformatic prediction of Major Histocompatibility Complex (MHC)
      epitopes.
AB  - Over the last 12 years, a large amount of knowledge has been accumulated on
      various aspects of Major Histocompatibility Complex (MHC) molecules. In
      conjunction, numerous algorithms and tools have been developed to screen protein
      molecules for these MHC receptor sites. By combining these computational tools
      and databases with genomic sequence information that is now widely available for
      a vast range of organisms, it is possible to screen whole genomes for MHC
      epitopes. By prescreening these genomes, it allows the researcher to narrow down
      possible protein targets for further analysis by traditional tools such as gene
      knockouts and animal efficacy studies. 

PMID- 23963947
TI  - Structure-based prediction of Major Histocompatibility Complex (MHC) epitopes.
AB  - Because of the enormous diversity of both MHC proteins and peptide epitopes,
      computational epitope prediction methods are needed in order to supplement
      limited experimental data. These prediction methods are useful for guiding
      experiments and have many potential biomedical applications. Unlike popular
      sequence-based methods, structure-based epitope prediction methods can predict
      epitopes for multiple MHC types with highly distinct peptide binding
      propensities. In this chapter, we describe in detail our previously developed
      structure-based epitope prediction methods for both class I and class II MHC
      proteins. We also discuss the relative advantages and disadvantages of sequence
      based versus structure-based methods and how to evaluate prediction performance. 

PMID- 23963948
TI  - Prioritization of therapeutic targets of inflammation using proteomics,
      bioinformatics, and in silico cell-cell interactomics.
AB  - Leukocyte extravasation is a multistep process, involving the movement of
      leukocytes out of the circulatory system, through vascular endothelium and to the
      site of tissue damage or infection. Protein-protein interactions play key roles
      in the extravasation process and have been attractive therapeutic targets for
      inhibiting inflammation using blocking (or neutralizing) antibodies. These
      targets include protein-protein interactions between cytokines (or chemokines)
      and their receptors on leukocytes and between adhesions molecules involving
      leukocyte-endothelium contacts. A number of therapeutics against these targets
      are currently used in clinic for treatment of inflammatory disorders, however,
      they are associated with side-effects partly due to the off-target actions (i.e.,
      nonspecific targets). There is a need for novel targets involved in the leukocyte
      extravasation process that are specific to leukocyte subsets or to individual
      inflammatory disorder, and are amenable for drug development (i.e., duggable). In
      this chapter, we describe a methodology to identify novel "druggable" targets
      involving protein-protein interactions between activated leukocytes and
      endothelial cells using a combination of proteomics, bioinformatics and in silico
      interactomics. The result is a prioritized list of protein-protein interactions
      in a network consisting of leukocyte-endothelial cell communication and contacts.
      These prioritized targets can be pursued for the development of therapeutics such
      as neutralizing antibodies and for their validation through preclinical testing.
      The method described here provides the workflow to identify and clinically target
      important cell-cell interactions that are specific/selective for particular
      inflammatory disorders and to improve currently available therapies. 

PMID- 23963949
TI  - Commercial considerations for immunoproteomics.
AB  - The underlying drivers of scientific processes have been rapidly evolving, but
      the ever-present need for research funding is typically foremost amongst these.
      Successful laboratories are embracing this reality by making certain that their
      projects have commercial value right from the beginning of the project
      conception. Which factors to be considered for commercial success need to be well
      thought out and incorporated into a project plan with similar levels of detail as
      would be the technical elements. Specific examples of commercial outcomes in the
      field of Immunoproteomics are exemplified in this discussion. 

PMID- 23963950
TI  - Bifidobacteria and humans: our special friends, from ecological to genomics
      perspectives.
AB  - Bifidobacteria are widely used as health-promoting microorganisms in many
      functional foods. However, the molecular mechanisms as to how these bacteria
      positively impact on host health are far from completely understood. For this
      reason these bacteria constitute a growing area of scientific interest with
      respect to their genomics, molecular biology and genetics. Genome sequencing of
      an increasing number of strains of bifidobacteria has provided access to the
      complete genetic make-up of many representative members of these bacteria. The
      aim of this review is to highlight the genetic and functional features of
      bifidobacteria residing in the human gastrointestinal tract using genomic and
      ecology-based information.

PMID- 23963951
TI  - Biophysical analysis of the putative acetyltransferase SACOL2570 from methicillin
      resistant Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of a myriad
      of insidious and intractable infections in humans, especially in patients with
      compromised immune systems and children. Here, we report the apo- and CoA-bound
      crystal structures of a member of the galactoside acetyltransferase superfamily
      from methicillin-resistant S. aureus SACOL2570 which was recently shown to be
      down regulated in S. aureus grown in the presence of fusidic acid, an antibiotic
      used to treat MRSA infections. SACOL2570 forms a homotrimer in solution, as
      confirmed by small-angle X-ray scattering and dynamic light scattering. The
      protein subunit consists of an N-terminal alpha-helical domain connected to a C
      terminal LbetaH domain. CoA binds in the active site formed by the residues from
      adjacent LbetaH domains. After determination of CoA-bound structure, molecular
      dynamics simulations were performed to model the binding of AcCoA. Binding of
      both AcCoA and CoA to SACOL2570 was verified by isothermal titration calorimetry.
      SACOL2570 most likely acts as an acetyltransferase, using AcCoA as an acetyl
      group donor and an as-yet-undetermined chemical moiety as an acceptor. SACOL2570
      was recently used as a scaffold for mutations that lead the generation of cage
      like assemblies, and has the potential to be used for the generation of more
      complex nanostructures. 

PMID- 23963952
TI  - Solution NMR structures provide first structural coverage of the large protein
      domain family PF08369 and complementary structural coverage of dark operative
      protochlorophyllide oxidoreductase complexes.
AB  - High-quality NMR structures of the C-terminal domain comprising residues 484-537
      of the 537-residue protein Bacterial chlorophyll subunit B (BchB) from Chlorobium
      tepidum and residues 9-61 of 61-residue Asr4154 from Nostoc sp. (strain PCC 7120)
      exhibit a mixed alpha/beta fold comprised of three alpha-helices and a small beta
      sheet packed against second alpha-helix. These two proteins share 29% sequence
      similarity and their structures are globally quite similar. The structures of
      BchB(484-537) and Asr4154(9-61) are the first representative structures for the
      large protein family (Pfam) PF08369, a family of unknown function currently
      containing 610 members in bacteria and eukaryotes. Furthermore, BchB(484-537)
      complements the structural coverage of the dark-operating protochlorophyllide
      oxidoreductase.

PMID- 23963953
TI  - The effect of age on illness cognition, subjective well-being and psychological
      distress among gastric cancer patients.
AB  - The current study examined illness cognition-thoughts and perceptions-patients
      hold regarding their illness and psychological adaptation in various age groups.
      More specifically, we aimed to examine whether illness cognition among cancer
      patients is related to their age. In addition, such association of illness
      cognition and age was also examined with respect to subjective well-being and
      psychological distress. A cross-sectional sample comprised of 123 consecutive
      post-treatment gastric outpatients. Their mean age was 57.31 (SD = 12.74), 56.9%
      (n = 70) were men and 81.3% (n = 100) were married. The results indicated a
      higher level of acceptance and a lower level of psychological distress among the
      young-old participants (60-69) compared with their counterparts. The oldest group
      (70+ years) had the highest level of helplessness and psychological distress, and
      the lowest level of acceptance, satisfaction and affect balance compared with the
      young-old participants. Among gastric cancer patients, age was found to be a
      factor relevant to the understanding of illness cognitions (acceptance and sense
      of helplessness) along with subjective well-being and psychological distress.
      These findings have practical implications for working with older cancer
      patients. Implications of these results are discussed.

PMID- 23963954
TI  - The gauntlet of peer review.

PMID- 23963955
TI  - Relationship between CYP1A2 localization and lipid microdomain formation as a
      function of lipid composition.
AB  - Cytochrome P450 (P450) function requires the interaction of P450 and NADPH
      cytochrome P450 reductase (CPR) in membranes, and is frequently studied using
      reconstituted systems composed solely of phosphatidylcholine. There is increasing
      evidence that other endoplasmic reticulum (ER) lipids can affect P450 structure,
      activity, and interactions with CPR. Some of these lipid effects have been
      attributed to the formation of organized liquid-ordered (l(o)) domains. The goal
      of this study was to determine if l(o) domains were formed in P450 reconstituted
      systems mimicking the ER membrane. CYP1A2, when incorporated in "ER-like" lipid
      vesicles, displayed detergent insolubility after treatment with Brij 98 and
      centrifugation in a sucrose gradient. Lipid probes were employed to identify
      domain formation in both ER-like vesicles and model membranes known to form l(o)
      domains. Changes in fluorescence resonance energy transfer (FRET) using an
      established donor/acceptor FRET pair in both ER-like and model l(o)-forming
      systems demonstrated the coexistence of l(o)- and liquid-disordered domains as a
      function of cholesterol and sphingomyelin content. Similarly, 6-dodecanoyl-2
      dimethylaminonaphthalene (laurdan), a probe that reports on membrane
      organization, showed that cholesterol and sphingomyelin increased membrane order.
      Finally, brominated-phosphatidylcholine allowed for monitoring of the location of
      both CPR and CYP1A2 within the l(o) regions of ER-like systems. Taken together,
      the results demonstrate that ER-like vesicles generate microdomains, and both
      CYP1A2 and CPR predominantly localize into l(o) membrane regions. Probe
      fluorescent responses suggest that lipid microdomains form in these vesicles
      whether or not enzymes are included in the reconstituted systems. Thus, it does
      not appear that the proteins are critical for stabilizing l(o) domains.

PMID- 23963957
TI  - Abstracts of the XXXVIIIth Sir Peter Freyer Memorial Lecture and Surgical
      Symposium 2013. September 6-7, 2013. Galway, Ireland.

PMID- 23963956
TI  - Theoretical and experimental analysis of the reaction mechanism of MrTPS2, a
      triquinane-forming sesquiterpene synthase from chamomile.
AB  - Terpene synthases, as key enzymes of terpene biosynthesis, have garnered the
      attention of chemists and biologists for many years. Their carbocationic reaction
      mechanisms are responsible for the huge variety of terpene structures in nature.
      These mechanisms are amenable to study by using classical biochemical approaches
      as well as computational analysis, and in this study we combine quantum-chemical
      calculations and deuterium-labeling experiments to elucidate the reaction
      mechanism of a triquinane forming sesquiterpene synthase from chamomile. Our
      results suggest that the reaction from farnesyl diphosphate to triquinanes
      proceeds through caryophyllyl and presilphiperfolanyl cations and involves the
      protonation of a stable (-)-(E)-beta-caryophyllene intermediate. A tyrosine
      residue was identified that appears to be involved in the proton-transfer
      process. 

PMID- 23963958
TI  - Hydrophilic interaction liquid chromatography coupled with MS/MS to detect and
      quantify dicarboxyethyl glutathione, a metabolic biomarker of the fumarate
      hydratase deficient cancer cell.
AB  - The identification of a glutathione (GSH) fumarate conjugate, dicarboxyethyl
      glutathione, formed during the nonenzymatic succination of GSH by fumarate was
      confirmed in fumarate hydratase deficient cells using a product ion scan approach
      followed by hydrophilic interaction liquid chromatography coupled with MS/MS. GSH
      and its conjugates, including dicarboxyethyl glutathione and glutathione
      disulfide, were successfully separated on a zwitterionic stationary phase and
      detected by MS/MS operated under negative ESI mode. The relative quantitation of
      the analytes in cell extracts was carried out and a correction model was
      established to determine correction factors under matrix effects and the response
      mismatch between the analytes. These factors were calculated and iteratively used
      to measure all analytes in cell extracts, based on calibration curves constructed
      in neat solution. The model was a closed-loop calculation, consisting of two
      sides with each side of the loop presenting a calculation pathway. Deviation of
      the correction factors obtained from these pathways manifested the model
      accuracy. The model was evaluated and there was no significant difference between
      the two pathways. 

PMID- 23963960
TI  - Parametric survival densities from phase-type models.
AB  - After a brief historical survey of parametric survival models, from actuarial,
      biomedical, demographical and engineering sources, this paper discusses the
      persistent reasons why parametric models still play an important role in
      exploratory statistical research. The phase-type models are advanced as a
      flexible family of latent-class models with interpretable components. These
      models are now supported by computational statistical methods that make numerical
      calculation of likelihoods and statistical estimation of parameters feasible in
      theory for quite complicated settings. However, consideration of Fisher
      Information and likelihood-ratio type tests to discriminate between model
      families indicates that only the simplest phase-type model topologies can be
      stably estimated in practice, even on rather large datasets. An example of a
      parametric model with features of mixtures, multiple stages or 'hits', and a
      trapping-state is given to illustrate simple computational tools in R, both on
      simulated data and on a large SEER 1992-2002 breast-cancer dataset. 

PMID- 23963959
TI  - Myocardial perfusion imaging with cardiac computed tomography: state of the art.
AB  - Cardiac computed tomography (CCT) has become an important tool for the anatomic
      assessment of patients with suspected coronary disease. Its diagnostic accuracy
      for detecting the presence of underlying coronary artery disease and ability to
      risk stratify patients are well documented. However, the role of CCT for the
      physiologic assessment of myocardial perfusion during resting and stress
      conditions is only now emerging. With the addition of myocardial perfusion
      imaging to coronary imaging, CCT has the potential to assess both coronary
      anatomy and its functional significance with a single non-invasive test. In this
      review, we discuss the current state of CCT myocardial perfusion imaging for the
      detection of myocardial ischemia and myocardial infarction and examine its
      complementary role to CCT coronary imaging. 

PMID- 23963961
TI  - Genetic testing practices for Charcot-Marie-Tooth type 1A disease.
AB  - INTRODUCTION: Charcot-Marie-Tooth disease type 1A (CMT1A) is caused by a PMP22
      gene duplication. CMT1A has a robust electrical phenotype that can be used to
      direct genetic testing. We compared specialty CMT center CMT1A diagnosis rates to
      those of outside physicians. METHODS: Charts were reviewed for 102 patients with
      CMT1A seen at a specialty CMT clinic between 2001 and 2009. Nerve conduction
      studies, family history, date of genetic testing, and type of genetic testing
      (single gene vs. panel) were collected. RESULTS: Although the specialty clinic
      ordered more PMP22 duplication testing alone beginning at an earlier year,
      thereby reducing costs, both the specialty clinic and outside physicians began
      the decade doing panel testing and ended the decade looking at only PMP22.
      CONCLUSIONS: Specialty centers adapt earlier to changes in testing practice than
      non-specialty centers. As the landscape of genetic testing changes, the
      algorithms for testing will also likely change.

PMID- 23963962
TI  - US-based emergency department visits for fluoroquinolone-associated
      hypersensitivity reactions.
AB  - PURPOSE: To estimate the rate of hypersensitivity reactions per 100,000
      prescription dispensings of fluoroquinolones based on care rendered in a
      nationally representative sample of US hospital emergency departments (ED).
      METHODS: We analyzed the frequency of fluoroquinolone-associated hypersensitivity
      reactions using the National Electronic Injury Surveillance System-Cooperative
      Adverse Drug Event Surveillance system (2004-2010) in conjunction with US retail
      outpatient prescription data from IMS Health (2004-2010). We further categorized
      reaction severity into three subgroups (mild, moderate, and severe). RESULTS:
      Based on 1422 cases of fluoroquinolone-associated hypersensitivity reactions and
      national drug utilization projections, we estimated risk of hypersensitivity
      reactions for moxifloxacin, ciprofloxacin, and levofloxacin. The absolute risk of
      a fluoroquinolone-related hypersensitivity reaction of any severity was low (44.0
      (95% CI 34.8-53.3) ED visits/100,000 prescriptions); however, we identified a
      statistically significant difference in the relative risk (rate ratios) of
      seeking care in an ED attributed to moxifloxacin hypersensitivity compared to
      either levofloxacin or ciprofloxacin. For all reaction severities, the estimated
      ED visits/100,000 prescriptions were 141.3 (95% CI 99.9-182.7) for moxifloxacin,
      40.8 (95% CI 31.5-50.0) for levofloxacin, and 26.3 (95% CI 20.8-31.9) for
      ciprofloxacin. When the rates were stratified by reaction severity category (mild
      or moderate-severe), moxifloxacin continued to be implicated in more ED visits
      per 100,000 prescriptions dispensed than either levofloxacin or ciprofloxacin.
      CONCLUSION: Fluoroquinolones may cause hypersensitivity reactions requiring care
      in an ED, and relative to use, the rate of moxifloxacin-related hypersensitivity
      reactions is higher compared to levofloxacin or ciprofloxacin.

PMID- 23963963
TI  - Enhancing neuronal growth from human endometrial stem cells derived neuron-like
      cells in three-dimensional fibrin gel for nerve tissue engineering.
AB  - Nerve tissue engineering (NTE) is one of the most promising methods to restore
      central nerve systems in human health care. Three-dimensional (3D) distribution
      and growth of cells within the porous scaffold composed of nanofibers are of
      clinical significance for NTE. In this study, an attempt was made to develop and
      characterize the use of fibrin gel and human endometrial stem cells (hEnSCs)
      derived neuron-like cells simultaneously to support cell behavior especially
      neuron outgrowth. The structural and mechanical characteristics of fibrin gel
      scaffold were examined with SEM and rheometer. Also, hEnSCs-derived neuron-like
      cells were cultured in fibrin gel and were subsequently analyzed with
      immunofluorescent staining against neuronal markers. In parallel, the survival
      and growth rates of the cells were determined by MTT assay and neurite extension.
      At the end, cell-matrix interactions were investigated with SEM and TEM
      micrographs. Mechanical properties of fabricated scaffold were studied and
      results indicated appropriate choice of material, SEM and TEM showed excellent
      integration of cells with nanofibers regarding the relation between cells and
      fibrin gel. Immunofluorescent staining of fibrin gel after 6 days of cell seeding
      and culture demonstrated well expanded and incorporated network of neurons. In
      addition, viability, proliferation, and neuronal growth of seeded cells were
      analyzed at days 1, 3, and 6. Comparing those results with 2D culture of seeded
      cells showed positive effect of 3D culture. Taken together, the results suggest
      that fibrin can provide a suitable, three-dimensional scaffold for neuronal
      survival and outgrowth for regeneration of the central nervous system.

PMID- 23963964
TI  - Interslice leakage artifact reduction technique for simultaneous multislice
      acquisitions.
AB  - PURPOSE: Controlled aliasing techniques for simultaneously acquired echo-planar
      imaging slices have been shown to significantly increase the temporal efficiency
      for both diffusion-weighted imaging and functional magnetic resonance imaging
      studies. The "slice-GRAPPA" (SG) method has been widely used to reconstruct such
      data. We investigate robust optimization techniques for SG to ensure image
      reconstruction accuracy through a reduction of leakage artifacts. METHODS: Split
      SG is proposed as an alternative kernel optimization method. The performance of
      Split SG is compared to standard SG using data collected on a spherical phantom
      and in vivo on two subjects at 3 T. Slice-accelerated and nonaccelerated data
      were collected for a spin-echo diffusion-weighted acquisition. Signal leakage
      metrics and time-series SNR were used to quantify the performance of the kernel
      fitting approaches. RESULTS: The Split SG optimization strategy significantly
      reduces leakage artifacts for both phantom and in vivo acquisitions. In addition,
      a significant boost in time-series SNR for in vivo diffusion-weighted
      acquisitions with in-plane 2* and slice 3* accelerations was observed with the
      Split SG approach. CONCLUSION: By minimizing the influence of leakage artifacts
      during the training of SG kernels, we have significantly improved reconstruction
      accuracy. Our robust kernel fitting strategy should enable better reconstruction
      accuracy and higher slice-acceleration across many applications.

PMID- 23963965
TI  - An open-label, rater-blinded, 8-week trial of bupropion hydrochloride extended
      release in patients with major depressive disorder with atypical features.
AB  - The present study aimed at investigating the effectiveness and tolerability of 
      bupropion hydrochloride extended release (XL) in major depressive disorder (MDD)
      patients with atypical features (AF).51 patients were prescribed bupropion XL for
      8 weeks (6 visits: screening, baseline, weeks 1, 2, 4 and 8). The primary
      efficacy measure was a change of the Structured Interview Guide for the Hamilton
      Depression Rating Scale-Seasonal Affective Disorder Version (SIGH-SAD) from
      baseline to endpoint. Secondary efficacy measures included the SIGH-SAD atypical
      symptoms subscale, Clinical Global Impression-Severity (CGI-S), Sheehan
      Disability Scale (SDS) and Epworth Sleepiness Questionnaire (ESQ). Response or
      remission was defined as >=50% reduction or <=7 in SIGH-SAD total scores,
      respectively, at end of treatment.The HAM-D-29 total score reduced by 55.3% from
      baseline (27.3+/-6.5) to end of treatment (12.2+/-6.3) (p<0.001). Atypical
      symptom subscale scores also reduced by 54.5% from baseline (9.2+/-3.0) to end of
      treatment (4.2+/-2.8) (p<0.001). At the end of treatment, 24.4% (n=10) and 51.2%
      (n=21) subjects were classified as remitters and responders, respectively. The
      most frequently reported AEs were headache (13.7%), dry mouth (11.8%), dizziness
      (9.8%), and dyspepsia (9.8%).Our preliminary study indicates that bupropion XL
      may be beneficial in the treatment of MDD with atypical features. Adequately
      powered, randomized, double-blind, placebo-controlled trials are necessary to
      determine our results. 

PMID- 23963966
TI  - Proteomic analysis of the dorsal and ventral hippocampus of rats maintained on a
      high fat and refined sugar diet.
AB  - The typical Western diet, rich in high saturated fat and refined sugar (HFS), has
      been shown to increase cognitive decline with aging and Alzheimer's disease, and
      to affect cognitive functions that are dependent on the hippocampus, including
      memory processes and reversal learning. To investigate neurophysiological changes
      underlying these impairments, we employed a proteomic approach to identify
      differentially expressed proteins in the rat dorsal and ventral hippocampus
      following maintenance on an HFS diet. Rats maintained on the HFS diet for 8 weeks
      were impaired on a novel object recognition task that assesses memory and on a
      Morris Water Maze task assessing reversal learning. Quantitative label-free
      shotgun proteomic analysis was conducted on biological triplicates for each
      group. For the dorsal hippocampus, 59 proteins were upregulated and 36
      downregulated in the HFS group compared to controls. Pathway ana-lysis revealed
      changes to proteins involved in molecular transport and cellular and molecular
      signaling, and changes to signaling pathways including calcium signaling, citrate
      cycle, and oxidative phosphorylation. For the ventral hippocampus, 25 proteins
      were upregulated and 27 downregulated in HFS fed rats. Differentially expressed
      proteins were involved in cell-to-cell signaling and interaction, and cellular
      and molecular function. Changes to signaling pathways included protein
      ubiquitination, ubiquinone biosynthesis, oxidative phosphorylation, and
      mitochondrial dysfunction. This is the first shotgun proteomics study to examine
      protein changes in the hippocampus following long-term consumption of a HFS diet,
      identifying changes to a large number of proteins including those involved in
      synaptic plasticity and energy metabolism. All MS data have been deposited in the
      ProteomeXchange with identifier PXD000028.

PMID- 23963967
TI  - Catalyst- and solvent-dependent stereodivergence in the intramolecular
      Et(2)Zn/Pd(0) -promoted carbonyl propargylation: mechanistic implications.
AB  - Carbonyl-tethered propargylic benzoates undergo intramolecular
      carbonylpropargylation upon treatment with Et2 Zn in the presence of a catalytic
      amount of Pd(0) with the formation of 2-alkynylcyclopentanol products. A
      ligand/solvent effect on the cis/trans selectivity (referring to the relative
      positions of alkynyl and OH groups) of ring-closure has been found. In a non
      coordinating solvent (benzene), increasing the electron-donating ability of the
      phosphine ligand (while decreasing its dissociation ability) leads to an
      increased tendency towards the trans product. On the other hand, the combination
      of a coordinating solvent (THF) and PPh3 , an easily dissociated phosphine,
      results in the exclusive formation of cis products. Experimental and
      computational results are compatible with a divergent behavior of an
      allenylethylpalladium intermediate that partitions between competitive carbonyl
      addition and transmetalation pathways, each leading to a different
      diastereoisomer. These results also suggest that the dissociating ability of the
      phosphine regulates that behavior. 

PMID- 23963968
TI  - Characterization of the human CD4(+) T-cell repertoire specific for major
      histocompatibility class I-restricted antigens.
AB  - While CD4(+) T lymphocytes usually recognize antigens in the context of major
      histocompatibility (MHC) class II alleles, occurrence of MHC class-I restricted
      CD4(+) T cells has been reported sporadically. Taking advantage of a highly
      sensitive MHC tetramer-based enrichment approach allowing detection and isolation
      of scarce Ag-specific T cells, we performed a systematic comparative analysis of
      HLA-A*0201-restricted CD4(+) and CD8(+) T-cell lines directed against several
      immunodominant viral or tumoral antigens. CD4(+) T cells directed against every
      peptide-MHC class I complexes tested were detected in all donors. These cells
      yielded strong cytotoxic and T helper 1 cytokine responses when incubated with
      HLA-A2(+) target cells carrying the relevant epitopes. HLA-A2-restricted CD4(+) T
      cells were seldom expanded in immune HLA-A2(+) donors, suggesting that they are
      not usually engaged in in vivo immune responses against the corresponding peptide
      MHC class I complexes. However, these T cells expressed TCR of very high affinity
      and were expanded following ex vivo stimulation by relevant tumor cells.
      Therefore, we describe a versatile and efficient strategy for generation of MHC
      class-I restricted T helper cells and high affinity TCR that could be used for
      adoptive T-cell transfer- or TCR gene transfer-based immunotherapies. 

PMID- 23963969
TI  - Notice of redundant publication.

PMID- 23963970
TI  - Perpetuating one's own disadvantage: intergroup contact enables the ideological
      legitimation of inequality.
AB  - Contact with the dominant group can increase opposition, among the disadvantaged,
      to social policies that would benefit their group. This effect can be explained
      in terms of contact promoting support for an ideology of meritocracy, which
      privileges the distribution of societal resources based on individual merit,
      rather than group-level disadvantage. We tested this ideological mechanism in a
      large, nationally representative sample of Maori (a disadvantaged group in New
      Zealand; N = 1,008). Positive intergroup contact with the dominant group (New
      Zealand Europeans) predicted increased opposition to a topical reparative policy
      (Maori ownership of the foreshore), and this was fully mediated by increased
      support for the ideology of meritocracy. Intergroup contact may enable the
      ideological legitimation of inequality among members of disadvantaged groups,
      engendering political attitudes that are detrimental to their group's interests.
      Contact with ingroup members had the opposite effect, increasing support for
      reparative policy by reducing subscription to meritocratic ideology. 

PMID- 23963971
TI  - Wealth and the inflated self: class, entitlement, and narcissism.
AB  - Americans may be more narcissistic now than ever, but narcissism is not evenly
      distributed across social strata. Five studies demonstrated that higher social
      class is associated with increased entitlement and narcissism. Upper-class
      individuals reported greater psychological entitlement (Studies 1a, 1b, and 2)
      and narcissistic personality tendencies (Study 2), and they were more likely to
      behave in a narcissistic fashion by opting to look at themselves in a mirror
      (Study 3). Finally, inducing egalitarian values in upper-class participants
      decreased their narcissism to a level on par with their lower-class peers (Study
      4). These findings offer novel evidence regarding the influence of social class
      on the self and highlight the importance of social stratification to
      understanding basic psychological processes. 

PMID- 23963972
TI  - Preconception health assessment in China, Lebanon and the Philippines:
      applicability to other countries.
AB  - To test the utility of a preconception checklist tool in identifying
      preconception health needs of women in three countries; China, Lebanon and the
      Philippines. An academic medical center within each country participated in the
      development and testing of a preconception checklist tool, which was administered
      over a 6 month period to selected target groups in each country. The checklist
      provided valuable data on the preconception health of 6,530 women. Aggregated
      data identified common preconception health needs across all countries, including
      provision of modern contraceptives and adequate immunization coverage; HIV and
      STI screening; treatment for anemia; and counseling for maintenance of a healthy
      weight. A preconception checklist tool was found to be useful in distinct
      cultural settings. The study was a pilot. Future steps include validation and
      standardization of the checklist, data from which could be used to help shape
      preconception care policies and implementation strategies. 

PMID- 23963973
TI  - Utility of minimum F-wave latencies compared with F-estimates and absolute
      reference values in S1 radiculopathies: are they still needed?
AB  - INTRODUCTION: The utility of F-waves in assessing radiculopathies is debated. The
      aim of this study is to determine the frequency of abnormal minimum tibial F-wave
      latencies compared to an F-estimate and an absolute reference value in patients
      with electromyography (EMG) confirmed S1 radiculopathies. METHODS: A
      retrospective review of F-waves in patients with an EMG-confirmed isolated S1
      radiculopathy was performed. The minimum and mean latencies of 8 tibial F-waves
      were compared with the calculated F-estimate and to an absolute reference value,
      and the frequencies of abnormal responses were determined. RESULTS: Of the 50
      patients with an S1 radiculopathy, 4% had prolongation of the minimum
      reproducible F-wave latency, and 8% had prolongation of the mean latency relative
      to the calculated F-estimate. CONCLUSIONS: The minimum and mean F-wave latencies
      are infrequently abnormal when compared with an estimated F-wave latency in S1
      radiculopathies and are insensitive in the assessment of S1 nerve root injury.

PMID- 23963976
TI  - Antithrombotic activities of oroxylin A in vitro and in vivo.
AB  - Here, the anticoagulant activities of oroxylin A (OroA), a major component of
      Scutellaria baicalensis Georgi, were examined by monitoring activated partial
      thromboplastin time (aPTT), prothrombin time (PT), and the activities of cell
      based thrombin and activated factor X (FXa). Furthermore, the effects of OroA on
      the expressions of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type
      plasminogen activator (t-PA) were tested in tumor necrosis factor (TNF)-alpha
      activated human umbilical vein endothelial cells (HUVECs). Treatment with OroA
      resulted in prolonged aPTT and PT and inhibition of the activities of thrombin
      and FXa, and OroA inhibited production of thrombin and FXa in HUVECs. And OroA
      inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In
      accordance with these anticoagulant activities, OroA elicited anticoagulant
      effects in mouse. In addition, treatment of OroA resulted in the inhibition of
      TNF-alpha-induced production of PAI-1, and treatment with OroA resulted in the
      significant reduction of the PAI-1 to t-PA ratio. Collectively, OroA possess
      antithrombotic activities and offer bases for development of a novel
      anticoagulant.

PMID- 23963977
TI  - The effective mechanism of the polysaccharides from Panax ginseng on chronic
      fatigue syndrome.
AB  - Ginseng acidic polysaccharide WGPA isolated from the root of Panax ginseng C. A.
      Meyer was fractionated into WGPA-A and WGPA-N by anion-exchange chromatography.
      The antifatigue activity of ginseng acidic polysaccharide WGPA has been reported
      in our previous research. This present study was designed to identify its active
      component and elucidate the mechanism for preventing chronic fatigue syndrome
      (CFS). WGPA, WGPA-A and WGPA-N were orally administered to mice once daily for 15
      days. The effects of these compounds on physiological biomarkers of oxidative
      stress and on the morphology of the mitochondria in striated skeletal muscle were
      assessed. The results of forced swimming test-induced indicated that WGPA and
      WGPA-A could lengthen the swimming time, while WGPA-N could not. In addition,
      malondialdehyde and lactate dehydrogenase levels in serum were enhanced; while
      those of superoxide dismutase and glutathione peroxidase were lowered.
      Interestingly, the structural degeneration of mitochondria were all ameliorated.
      These findings suggested that WGPA-A is the active component of WGPA, it might
      have potential therapeutic effects for CFS and the oxidative stress might be
      involved in the pathogenesis. Our results also provided essential data for a
      better understanding of the antifatigue effects of P. ginseng extracts.

PMID- 23963978
TI  - 7 Tesla MRI with a transmit/receive loopless antenna and B1-insensitive selective
      excitation.
AB  - PURPOSE: Use of external coils with internal detectors or conductors is
      challenging at 7 Tesla (T) due to radiofrequency (RF) field (B1 ) penetration, B1
      -inhomogeneity, mutual coupling, and potential local RF heating. The present
      study tests whether the near-quadratic gains in signal-to-noise ratio and field
      of-view with field-strength previously reported for internal loopless antennae at
      7T can suffice to perform MRI with an interventional transmit/receive antenna
      without using any external coils. METHODS: External coils were replaced by semi
      rigid or biocompatible transmit/receive loopless antennae requiring only a few
      Watts of peak RF power. Slice selection was provided by spatially selective B1 
      insensitive composite RF pulses that compensate for the antenna's intrinsically
      nonuniform B1 -field. Power was adjusted to maintain local temperature rise <=1
      degrees C. Fruit, intravascular MRI of diseased human vessels in vitro, and MRI
      of rabbit aorta in vivo are demonstrated. RESULTS: Scout MRI with the
      transmit/receive antennae yielded a <=10 cm cylindrical field-of-view, enabling
      subsequent targeted localization at ~100 MUm resolution in 10-50 s and/or 50 MUm
      MRI in ~2 min in vitro, and 100-300 MUm MRI of the rabbit aorta in vivo.
      CONCLUSION: A simple, low-power, one-device approach to interventional MRI at 7T
      offers the potential of truly high-resolution MRI, while avoiding issues with
      external coil excitation and interactions at 7T.

PMID- 23963979
TI  - Aligned SF/P(LLA-CL)-blended nanofibers encapsulating nerve growth factor for
      peripheral nerve regeneration.
AB  - Artificial nerve guidance conduits (NGCs) containing bioactive neurotrophic
      factors and topographical structure to biomimic native tissues are essential for
      efficient regeneration of nerve gaps. In this study, aligned SF/P(LLA-CL)
      nanofibers encapsulating nerve growth factor (NGF), which was stabilized by SF in
      core, were fabricated via a coaxial electrospinning technique. The controlled
      release of NGF from the nanofibers was evaluated using enzyme-linked immune
      sorbent assay (ELISA) and PC12 cell-based bioassay over a 60-day time period. The
      results demonstrated that NGF presented a sustained release and remained
      biological activity over 60 days. Nerve guidance conduits (NGCs) were fabricated
      by reeling the aligned SF/P(LLA-CL) nanofibrous scaffolds encapsulating NGF and
      then used as a bridge implanted across a 15-mm defect in the sciatic nerve of
      rats to promote nerve regeneration. The outcome in terms of regenerated nerve at
      12 weeks was evaluated by a combination of electrophysiological assessment,
      histochemistry, and electron microscopy. All results clarified that the NGF
      encapsulated-aligned SF/P(LLA-CL) NGCs promoted peripheral nerve regeneration
      significantly better than the aligned SF/P(LLA-CL) NGCs, suggesting that the
      released NGF from nanofibers could effectively promote the regeneration of
      peripheral nerve.

PMID- 23963980
TI  - [Guest editorial ZfOU -- congress Issue].

PMID- 23963981
TI  - [Angular and sliding stable internal fixation of proximal humerus fractures using
      the "Varion" intramedullary nail].
AB  - BACKGROUND: Intramedullary angular and sliding stable interlocking nails are
      attracting increasing attention in the treatment of fractures of the proximal
      humerus. This prospective study evaluates the clinical and radiological outcome
      of the "Varion" nail osteosynthesis system. Additionally we analysed the impact
      of the postoperative head-shaft angle on the functional outcome. PATIENTS AND
      METHODS: We examined 61 patients who were treated with a Varion nail and were re
      evaluated after an average follow-up period of 7.1 months. We assessed the pre
      trauma DASH score and the Constant score of the non-injured side. We also
      measured the postoperative radiographic head-shaft angle. At the follow-up exam
      we determined the DASH and Constant scores of the treated extremity and made
      control radiographs. RESULTS: We were able to re-evaluate 54 patients. The DASH
      score at follow-up averaged 19.3 and the mean postoperative Constant score
      reached 67.4 points and thus 81.1 % of the score of the non-injured side. The
      average pain level was 1.3 on the VAS. A high patient satisfaction was obtained.
      There was a significant correlation between the complexity of the fracture and
      the clinical outcome. The best functional result was seen when the postoperative
      head-shaft angle was between 140 and 151 degrees . There were 7 cases of
      postoperative complications, in 5 of these cases minor revision surgeries were
      carried out. CONCLUSION: The "Varion nail" provides safe and effective treatment
      of even complicated proximal humerus fractures with good clinical and functional
      results. The optimum angle between head and shaft axis lies between 141 and 150
      degrees .

PMID- 23963982
TI  - [Simple pelvic fracture - presentation of life-threatening complications and
      their therapy].
AB  - The risk of life-threatening bleeding in stable pelvic-ring fractures is often
      underestimated. The angioembolisation is, in these cases, an important treatment
      option. Two case reports illustrate the risks of such haemorrhagic complications
      in stable pelvic-ring fractures and their immediate treatment. The fracture
      itself can often be treated conservatively and does not require treatment in a
      trauma centre. However, in the case of haemorrhage complications such treatment
      seems to be essential. 

PMID- 23963983
TI  - [Treatment of septic olecranon and patellar bursitis by excision and vacuum
      assisted closure therapy].
AB  - BACKGROUND: Treatment of septic olecranon and patellar bursitis differs
      considerably and is currently under discussion. We therefore performed a
      retrospective study of our patients with septic bursitis in the past 5 years.
      PATIENTS AND METHOD: Between March 2007 and February 2012 we treated 79 patients
      with septic olecranon (n = 43) and patellar (n = 36) bursitis surgically: 61
      males, 18 females, age 51 (range: 11-91) years. Four patients had not been
      treated before, 25 had suffered recurrences after 1-10 previous procedures, and 9
      patients had not improved after conservative therapy. 34 patients presented with
      traumatic rupture or fistula of their bursae. In all cases we performed a radical
      bursectomy and vacuum-assisted therapy for 4 to 5 days. In addition, patients
      received systemic antibiotics. We phoned all patients and were successful in 57
      cases (72 %). We questioned these patients for range of movement, limitations at
      work, pain, sensibility disorder, satisfaction with the result and further
      surgical procedures. In all cases we took tissue specimens for cultures, in 48
      preparations histological examination was performed. RESULTS: Microbiological and
      histological results are discussed in detail. 40 patients were free of
      complaints, 15 complained of mild pain, 54 of 57 had unlimited range of motion.
      Minor discomforts at desk work were reported by 5 of 43 patients, 12 out of 36
      patient reported discomfort when performing on their knees. There was no
      recurrence in the period of investigation. CONCLUSION: We recommend our treatment
      concept for septic olecranon and patellar bursitis because patient satisfaction
      is high and recurrences are reliably avoided. The soft tissue is spared, so that
      plastic covering procedures are seldom necessary.

PMID- 23963984
TI  - [Growth and deformity after in situ fixation of slipped capital femoral
      epiphysis].
AB  - BACKGROUND: For mild to moderate slipped capital femoral epiphysis (SCFE) in situ
      fixation is the current treatment standard. However, concerning the implant
      selection (screw versus k-wires) as well as the prophylactic stabilisation of the
      non-affected hip, controversies still exist. The aim of this study was to analyse
      femoral residual growth and femoral deformities after in situ fixation of SCFE
      either with k-wires or screws. PATIENTS AND METHODS: We conducted a retrospective
      analysis of the radiographs of adolescents treated for SCFE in our department
      between 01/2003 and 02/2011. To evaluate femoral growth the articulo-trochanteric
      distance, centro-trochanteric distance, caput-collum-diaphyseal angle, pin-joint
      ratio and pin-physis ratio were determined. The femoral deformity was assessed by
      measuring the sphericity of the femoral head. Degenerative changes were evaluated
      in the final radiographs. Statistical analysis was performed concerning
      differences between therapeutically and prophylactically treated hips as well as
      stabilisations with k-wires and screws. RESULTS: A total of 22 patients (female :
      male = 14 : 8, mean age girls: 11 +/- 1 years, boys: 13 +/- 2 years) with 26
      slipped capital femoral epiphyses was analysed. K-wires were used for fixation in
      4 hips each therapeutically and prophylactically, 22 hips with SCFE and 14 non
      affected hips were stabilised with screws. Treatment with screws did not lead to
      significantly earlier physeal closure than k-wire pinning. Regarding the femoral
      growth parameters a significant decrease in the articulo-trochanteric distance
      and CCD angle was detectable in all groups. The pin-joint ratio revealed an
      adequate residual growth in 58 % of the therapeutically and in 72 % of the
      prophylactically treated hips without significant difference between k-wires and
      screws. The pin-physis ratio demonstrated similar values. Regarding the femoral
      deformity the SCFE hips resulted in a significantly reduced sphericity, which
      remained unchanged during follow-up. The prophylactic stabilisation did not
      result in any deterioration of sphericity. CONCLUSION: The results of this study
      imply that further growth of the proximal femur after insertion of a sliding
      screw for in situ stabilisation of mild to moderate slipped capital femoral
      epiphysis does occur. Furthermore, an increase of deformity during follow-up
      through screw fixation as compared to pinning was not noticed. Hence, the
      assumption that screw fixation leads to permanent physeal impairment cannot be
      confirmed. The consideration of these results may be helpful for implant
      selection as well as indicating prophylactic surgery for non-affected hips.

PMID- 23963985
TI  - [Diagnostic and therapeutic management of primary and recurrent patellar
      dislocations - analysis of a nationwide survey and the current literature].
AB  - AIM: Patellar dislocations are a common injury of the knee joint. During patella
      dislocations injuries of soft-tissue structures can occur that can destabilise
      the patella and lead to recurrent dislocations. There are also congenital
      pathologies that predispose to patella dislocations. In the current literature,
      diagnostics and treatment of patellar dislocations are frequently discussed.
      Therefore the aim of our survey was to analyse and summarise actual diagnostic
      and therapeutic strategies regarding primary and recurrent patella dislocations.
      METHODS: An online questionnaire form was sent to 735 orthopaedic and/or trauma
      departments in Germany. The departments were invited to participate in an
      anonymous survey concerning diagnostics and treatment of primary and recurrent
      patellar dislocations. The questionnaire consisted of multiple choice questions
      and was divided into three sections. The first section included questions
      concerning the department structure. The second part contained questions
      regarding diagnostics and treatment of primary patella dislocations. The third
      part involved diagnostic and treatment strategies for recurrent patella
      dislocations. A systematic review of outcome after treatment of patellar
      dislocation was performed and discussed with the results of the survey. RESULTS:
      245 hospitals (33.3 %) returned the questionnaire. Among the participants were 23
      % orthopaedic surgery departments, 32 % trauma surgery departments and 45 %
      combined departments. 12 % were university hospitals and 53 % academic teaching
      hospitals. Clinical examination was performed by nearly all participants after
      primary and recurrent patella dislocations. MRI was used as diagnostic tool in 81
      % after primary patella dislocation and in 85 % after recurrent patella
      dislocation. Conventional X-rays were performed in 58 % (primary) and 51 %
      (recurrent patella dislocations). Computed tomography scans for measurement of
      the tuberositas tibiae-trochlea groove distance were used in 35 % after recurrent
      dislocations and in 20 % after primary patella dislocations. 69 % of the
      participating departments performed non-operative therapies after primary patella
      dislocations, especially when no associated injuries and no congenital
      pathologies were observed. Reconstruction of the medial retinaculum was the most
      frequent surgical therapy (52 %) followed by the reconstruction of the medial
      patellofemoral ligament (36 %) after primary patella dislocation. Following
      recurrent patella dislocations reconstruction of the medial patellofemoral
      ligament (58.5 %) was the most performed surgery and a tuberositas transfer was
      done in 58 % of participating departments after recurrent patella dislocation.
      CONCLUSION: The results of our survey showed diagnostic and therapeutic
      procedures in the participating departments which are in accordance with
      recommendations in recent publications. The clinical importance of the MPFL
      reconstruction was observed for primary and recurrent patella dislocation. In
      addition, conservative treatment is still the most common treatment after primary
      dislocation of the patella.

PMID- 23963986
TI  - [Practical courses for students can not only improve the teaching quality but can
      also increase the attractiveness of orthopaedic and trauma surgery].
AB  - BACKGROUND: Students often complain about a lack of teaching of practical skills.
      This may be a cause for the low attractiveness of surgical disciplines. We
      therefore established a practical course to improve teaching quality to inspire
      the students for orthopedic and trauma surgery. METHODS: The platforms of the
      course included the teaching and acquisition of suture techniques, arthroscopy
      and osteosynthesis techniques. A total of 119 students participated in 9 courses
      and performed a detailed evaluation. RESULTS: The main motivation to participate
      was (i) to acquire practical skills (93 %), (ii) to learn about orthopaedic and
      trauma surgery (66 %) and (iii) to facilitate decision-making for the
      occupational choice (21 %). 94 % judged the quality of the course as "excellent",
      and all 119 participants indicated that they would recommend the course to other
      students. 43 of 45 students, who had not yet decided on their occupational
      choice, indicated that the course stimulated them for a career in orthopaedic and
      trauma surgery. CONCLUSION: This course not only can improve the teaching quality
      but also can increase the attractiveness of muskuloskeletal surgery.

PMID- 23963987
TI  - [Re-evaluation of the AOK hospital navigator with a focus on total knee
      replacement].
AB  - BACKGROUND: One of the biggest health insurance companies in Germany (AOK,
      Allgemeine Ortskrankenkasse) has published new results focussing on process
      quality of total knee replacement in 2010. These results were published in the
      online portal "Weibetae Liste", which is based on health insurance routine data.
      The German Association of Orthopeadic Surgery questions the credibility of the
      rating system of the "Weibetae Liste". To prove the system an interdisciplinary
      task force was created. MATERIAL AND METHODS: The task force identified patient
      specific parameters, which influence the outcome of total knee replacement based
      on the literature and expert opinions. Out of 907 orthopaedic departments, 4
      above average and four below average were identified. The AOK was asked to
      provide 80 data sets for each department. These anonymised data sets could be
      converted into patient-specific data sets in the identified departments.
      Statistical analysis was performed to answer the question of whether there are
      differences between the below and the above average groups. RESULTS: 625 cases
      could be investigated. We found an increased rate of postoperative complications
      in the below average group. There are differences between both groups in terms of
      factors influencing the procedure. In the below average group an increased rate
      of patients with one or more comorbidities and a preoperative extension lag of
      over 10 degrees  was found. The above average group has a higher rate of
      operations before the knee replacement. CONCLUSION: The results need to be proven
      on a larger scale. Further, prospective investigations are planned.

PMID- 23963988
TI  - [Orthopedic rheumatology].
AB  - Rheumatic diseases with their progressive inflammatory systematic nature are
      important diseases any clinical practising orthopaedic doctor is frequently
      confronted with. In case of mono- or polyarticular joint swelling, stiffness or
      inflammatory arthralgia, rheumatoid arthritis has to be deliberated particularly
      in differential diagnostic considerations. When diagnosed early, a joint
      treatment by an internal specialist as well as the initiation of a basic
      medicamentous therapy are highly recommended. Therefore, corticosteroids and
      disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate can be used,
      in case of failure a treatment with biologicals should follow. The operative
      therapy depends on the stadium of joint destruction. In early stadiums (LDE 0-3)
      and in case of therapy resistant inflammation a synovectomy should be performed
      as a preventive intervention. Given an already advanced destruction,
      alloarthroplasty or arthrodesis are indicated as reconstructive procedures. 

PMID- 23963989
TI  - Functionalized organotin-chalcogenide complexes that exhibit defect heterocubane
      scaffolds: formation, synthesis, and characterization.
AB  - The synthesis of new functionalized organotin-chalcogenide complexes was achieved
      by systematic optimization of the reaction conditions. The structures of
      compounds [(R(1, 2) Sn)3 S4 Cl] (1, 2), [((R(2) Sn)2 SnS4 )2 (MU-S)2 ] (3),
      [(R(1, 2) Sn)3 Se4 ][SnCl3 ] (4, 5), and [Li(thf)n ][(R(3) Sn)(HR(3) Sn)2 Se4 Cl]
      (6), in which R(1) =CMe2 CH2 C(O)Me, R(2) =CMe2 CH2 C(NNH2 )Me, and R(3) =CH2 CH2
      COO, are based on defect heterocubane scaffolds, as shown by X-ray diffraction,
      (119) Sn NMR spectroscopy, and ESI mass spectrometry analyses. Compounds 4, 5,
      and 6 constitute the first examples of defect heterocubane-type metal
      chalcogenide complexes that are comprised of selenide ligands. Comprehensive DFT
      calculations prompted us to search for the formal intermediates [(R(1) SnCl2 )2
      (MU-S)] (7) and [(R(1) SnCl)2 (MU-S)2 ] (8), which were isolated and helped to
      understand the stepwise formation of compounds 1-6. 

PMID- 23963990
TI  - Methionine and methionine sulfoxide alter parameters of oxidative stress in the
      liver of young rats: in vitro and in vivo studies.
AB  - It has been shown that elevation of plasma methionine (Met) and its metabolites
      may occur in several genetic abnormalities. In this study we investigated the in
      vitro and in vivo effects of the Met and methionine sulfoxide (MetO) on oxidative
      stress parameters in the liver of rats. For in vitro studies, liver homogenates
      were incubated with Met, MetO, and Mix (Met + MetO). For in vivo studies, the
      animals were divided into groups: saline, Met 0.4 g/kg, MetO 0.1 g/kg, and Met
      0.4 g/kg + MetO 0.1 g/kg. The animals were euthanized 1 and 3 h after injection.
      In vitro results showed that Met 1 and 2 mM and Mix increased catalase (CAT)
      activity. Superoxide dismutase (SOD) was enhanced by Met 1 and 2 mM, MetO 0.5 mM,
      and Mix. Dichlorofluorescein oxidation was increased by Met 1 mM and Mix. In vivo
      results showed that Met, MetO, and Mix decreased TBARS levels at 1 h. Total thiol
      content decreased 1 h after and increased 3 h after MetO and Met plus MetO
      administrations. Carbonyl content was enhanced by Met and was reduced by MetO 1 h
      after administration. Met, MetO and Met plus MetO decreased CAT activity 1 and 3
      h after administration. Furthermore, only MetO increased SOD activity. In
      addition, Met, MetO, and Mix decreased dichlorofluorescein oxidation at 1 and 3
      h. Our data indicate that Met/MetO in vivo and in vitro modify liver homeostasis
      by altering the redox cellular state. However, the hepatic changes caused by
      these compounds suggest a short-time adaptation of this tissue. 

PMID- 23963991
TI  - Structure-activity relationships of alphas-casein peptides with multifunctional
      biological activities.
AB  - Multifunctional bioactive peptides have a wider role in modulating physiological
      functions and possess multiple biological activities. Peptides from bovine milk
      with sequences QKALNEINQF [p10] and TKKTKLTEEEKNRL [p14] from alpha-S2 casein f
      (79-88) and alpha-S2 casein f (148-161) were identified to be having
      multifunctional biological activities and were synthesized. These synthesized
      peptides show various biological activities like angiotensin-converting enzyme
      inhibition, prolyl endopeptidase inhibition, antioxidant, and antimicrobial
      activities. The mode of antimicrobial mechanism was studied and p10 shows
      depolarization of cell membrane, whereas p14 was found to display DNA-binding
      activity. Structural studies envisaged backbone flexibility, for differences in
      their mode of action. Peptide structure function studies were correlated to
      understand their multifunctional biological activity. 

PMID- 23963992
TI  - Silymarin- and melatonin-mediated changes in the expression of selected genes in
      pesticides-induced Parkinsonism.
AB  - Parkinson's disease (PD) is the second most unconcealed neurodegenerative
      disorder labelled with motor impairments. Two pesticides, manganese ethylene-1,2
      bisdithiocarbamate (maneb) and 1,1'-dimethyl-4,4'-bipyridinium dichloride
      (paraquat), together, are reported to increase the incidence of PD in humans and
      Parkinsonism in mice. Conversely, silymarin and melatonin, two naturally
      occurring antioxidants, rescue from maneb- and paraquat-induced Parkinsonism. The
      study examined silymarin- and melatonin-mediated changes in the expression of
      selected genes in maneb- and paraquat-induced Parkinsonism employing mouse
      discover chips microarrays. The mice were treated intraperitoneally (i.p.),
      daily, with silymarin (40 mg/kg) or melatonin (30 mg/kg) for 9 weeks along with
      vehicles. Subsets of animals were also treated with maneb (30 mg/kg; i.p.) and
      paraquat (10 mg/kg; i.p.), twice a week, for 9 weeks. Whilst the expression of
      genes in the striatum was determined by microarray, the expression of randomly
      selected transcripts was validated by quantitative real-time polymerase chain
      reaction (qRT-PCR). Combined maneb- and paraquat-treatment altered the expression
      of several genes associated with apoptosis, inflammation, cell cycle, cell
      signalling, etc. pathways. Silymarin and melatonin significantly resisted the
      changes in the expression of a few genes related to apoptosis, inflammation, cell
      cycle, cell-signalling, etc. The expression patterns of seven randomly selected
      genes were analyzed by qRT-PCR, which were found to follow the similar trends, as
      observed with microarray. The results obtained from the study thus demonstrate
      that despite resemblances, silymarin and melatonin differentially offset maneb-
      and paraquat-induced changes in transcriptome. 

PMID- 23963993
TI  - Rotenone-induced oxidative stress and apoptosis in human liver HepG2 cells.
AB  - Rotenone, a commonly used pesticide, is well documented to induce selective
      degeneration in dopaminergic neurons and motor dysfunction. Such rotenone-induced
      neurodegenration has been primarily suggested through mitochondria-mediated
      apoptosis and reactive oxygen species (ROS) generation. But the status of
      rotenone induced changes in liver, the major metabolic site is poorly
      investigated. Thus, the present investigation was aimed to study the oxidative
      stress-induced cytotoxicity and apoptotic cell death in human liver cells-HepG2
      receiving experimental exposure of rotenone (12.5-250 MUM) for 24 h. Rotenone
      depicted a dose-dependent cytotoxic response in HepG2 cells. These cytotoxic
      responses were in concurrence with the markers associated with oxidative stress
      such as an increase in ROS generation and lipid peroxidation as well as a
      decrease in the glutathione, catalase, and superoxide dismutase levels. The
      decrease in mitochondrial membrane potential also confirms the impaired
      mitochondrial activity. The events of cytotoxicity and oxidative stress were
      found to be associated with up-regulation in the expressions (mRNA and protein)
      of pro-apoptotic markers viz., p53, Bax, and caspase-3, and down-regulation of
      anti-apoptotic marker Bcl-2. The data obtain in this study indicate that rotenone
      induced cytotoxicity in HepG2 cells via ROS-induced oxidative stress and
      mitochondria-mediated apoptosis involving p53, Bax/Bcl-2, and caspase-3. 

PMID- 23963994
TI  - CK2 kinase activity but not its binding to CK2 promoter regions is implicated in
      the regulation of CK2alpha and CK2beta gene expressions.
AB  - Protein kinase CK2, a ubiquitous serine/threonine kinase in control of a variety
      of crucial cellular functions, is composed of catalytic alpha- and alpha'
      subunits and non-catalytic beta-subunits which form holoenzymes such as
      CK2(alphabeta)2, CK2alphaalpha'beta2, or CK2(alpha'beta)2. In addition, there is
      ample evidence for the occurrence of the individual subunits beside the
      holoenzyme. While the CK2 subunits are well analyzed on the protein level, only
      little is known about the regulation of their transcription. The existence of
      multiple forms of CK2 subunits raised the question about a mutual regulation of
      their expression. Here we defined two 5'-upstream regions of the CK2alpha and the
      CK2beta genes, respectively, as sequences with promoter activities. We found that
      CK2alpha and CK2alpha' stimulated the expression of the reporter constructs
      whereas, CK2beta was inactive. Using chromatin immunoprecipitation assays, we
      were unable to detect binding of endogenous CK2 subunits to these promoter
      sequences in vivo. However, it turned out that inhibition of the kinase activity
      of CK2 attenuated the promoter activity indicating that CK2alpha and CK2alpha'
      might regulate their gene expression indirectly by phosphorylation reactions.
      Thus, we have shown here (i) that under normal physiological conditions CK2 does
      not bind to CK2 promoter regions and (ii) that the CK2 kinase activity is
      implicated in the regulation of its own expression. 

PMID- 23963995
TI  - Systemic minor histocompatibility antigen expression in blood endothelial cells
      prevents T cell-mediated vascular immunopathology.
AB  - Attenuation of T cell-mediated damage of blood endothelial cells (BECs) in
      transplanted organs is important to prevent transplant vasculopathy (TV) and
      chronic rejection. Here, we assessed the importance of minor histocompatibility
      antigen (mHA) distribution and different coinhibitory molecules for T cell-BEC
      interaction. A transgenic mHA was directed specifically to BECs using the Tie2
      promoter and cellular interactions were assessed in graft-versus-host disease
      like and heterotopic heart transplantation settings. We found that cognate CD4(+)
      T-cell help was critical for the activation of BEC-specific CD8(+) T cells.
      However, systemic mHA expression on BECs efficiently attenuated adoptively
      transferred, BEC-specific CD4(+) and CD8(+) T cells and hence prevented tissue
      damage, whereas restriction of mHA expression to heart BECs precipitated the
      development of TV. Importantly, the lack of the coinhibitory molecules programmed
      death-1 (PD-1) and B and T lymphocyte attenuator fostered the initial activation
      of BEC-specific CD4(+) T cells, but did not affect development of TV. In
      contrast, TV was significantly augmented in the absence of PD-1 on BEC-specific
      CD8(+) T cells. Taken together, these results indicate that antigen distribution
      in the vascular bed determines the impact of coinhibition and, as a consequence,
      critically impinges on T cell-mediated vascular immunopathology.

PMID- 23963996
TI  - Lung cancer with gastrointestinal metastasis - review of theories of metastasis
      with three rare case descriptions.
AB  - Approximately 1 in 14 men and women during their lifetime will be diagnosed with
      lung cancer, which is the leading cause of cancer-related mortality in the world.
      As of January 1, 2008, there were about 373,500 men and women living with lung
      cancer in the United States. Fewer than 60,000 of these are estimated to be alive
      by January 2013, reflecting a poor overall 5-year relative survival rate of under
      16 %. With metastatic cancer, the overall 5-year survival is meager 4 %. On the
      other hand, the overall five-year survival is over 50 % when the cancer is still
      in the localized stage. However, unfortunately, more than half of cases of lung
      cancer are diagnosed at an advanced stage Howlader et al. (2010). Cancer
      metastasis, the single most critical prognostic factor, is still poorly
      understood and a highly complex phenomenon. The most common sites of lung cancer
      metastasis are the lymph nodes, liver, adrenals, brain and bones. The
      gastrointestinal (GI) tract is an exceptionally rare site of metastasis; with
      only a handful of cases reported in the literature Centeno et al. (Lung Cancer,
      18: 101-105, 1997); Hirasaki et al. (World J Gastroenterol, 14: 5481-5483, 2008);
      Carr and Boulos (Br J Surg, 83: 647, 1996); Otera et al. (Eur Respir Rev, 19: 248
      252, 2010); Antler et al. (Cancer, 49: 170-172, 1982); Fujiwara et al. (Gen
      Thorac Cardiovasc Surg, 59: 748-752, 2011); Stinchcombe et al. (J Clin Oncol, 24:
      4939-4940, 2006); John et al. (J Postgrad Med, 48: 199-200, 2002); Carroll and
      Rajesh (Eur J Cardiothorac Surg, 19: 719-720, 2001); Brown et al. (Dis Colon
      Rectum, 23: 343-345, 1980). We report three cases of non-small cell (squamous
      cell) lung cancer with GI tract metastasis-two in the colon and one in the
      jejunum. Then we present a review of literature exploring various theories of
      metastasis, as an attempt to understand the reason of preferential tumor
      metastasis. 

PMID- 23963997
TI  - Morphology and expression status investigations of specific surface markers on B
      cell chronic lymphocytic leukemia cells.
AB  - The morphology of cells and expression status of specific surface markers
      [cluster of differentiation (CD)], such as CD5, CD19, CD20, CD38, and CD45, have
      long been considered as the essential indicators for the diagnosis and prognosis
      of B-cell chronic lymphocytic leukemia (B-CLL). Clinically, it is difficult to
      simultaneously obtain cell morphology and distribution of surface markers with
      flow cytometry, especially for some surrogate markers such as CD38. Here, as an
      alternative and complementary prognostic method, fluorescence microscopy and
      image processing method are introduced to directly visualize the cells from
      patients and to quantitatively determine the expression status of surface
      markers. In this study, the morphological parameters of B-CLL cells were measured
      to establish the correlation between the cellular morphology and the surface
      marker expression. It was clear that the CD38+ and CD38- B-CLL cells from the
      same CD38+ patients had hardly any size differences; however, an increase in
      perimeter was observed for CD38- patients. Moreover, the expression level of the
      receptors on the cell was independent of the cell size. There was no evidence
      showing that the expression intensities of CD19 and CD38 were related to each
      other for the CD38+ B-CLL cells. On the same cells, CD5 was more selectively
      expressed on the cell membrane; however, the expression patterns suggested that
      the cell membrane of CD38- B-CLL cells contained the least expression level of
      CD19.

PMID- 23963998
TI  - Nineteen-channel receive array and four-channel transmit array coil for cervical
      spinal cord imaging at 7T.
AB  - PURPOSE: To design and validate a radiofrequency (RF) array coil for cervical
      spinal cord imaging at 7T. METHODS: A 19-channel receive array with a four
      channel transmit array was developed on a close-fitting coil former at 7T.
      Transmit efficiency and specific absorption rate were evaluated in a B1 (+)
      mapping study and an electromagnetic model. Receive signal-to-noise ratio (SNR)
      and noise amplification for parallel imaging were evaluated and compared with a
      commercial 3T 19-channel head-neck array and a 7T four-channel spine array. The
      performance of the array was qualitatively demonstrated in human volunteers using
      high-resolution imaging (down to 300 MUm in-plane). RESULTS: The transmit and
      receive arrays showed good bench performance. The SNR was approximately 4.2-fold
      higher in the 7T receive array at the location of the cord with respect to the 3T
      coil. The g-factor results showed an additional acceleration was possible with
      the 7T array. In vivo imaging was feasible and showed high SNR and tissue
      contrast. CONCLUSION: The highly parallel transmit and receive arrays were
      demonstrated to be fit for spinal cord imaging at 7T. The high sensitivity of the
      receive coil combined with ultra-high field will likely improve investigations of
      microstructure and tissue segmentation in the healthy and pathological spinal
      cord.

PMID- 23963999
TI  - Some more evidence of long-term psychosocial harms from receiving false-positive
      screening mammography results.

PMID- 23964000
TI  - Physically developed and exploratory young infants contribute to their own long
      term academic achievement.
AB  - A developmental cascade defines a longitudinal relation in which one
      psychological characteristic uniquely affects another psychological
      characteristic later in time, separately from other intrapersonal and
      extrapersonal factors. Here, we report results of a large-scale (N = 374),
      normative, prospective, 14-year longitudinal, multivariate, multisource,
      controlled study of a developmental cascade from infant motor-exploratory
      competence at 5 months to adolescent academic achievement at 14 years, through
      conceptually related and age-appropriate measures of psychometric intelligence at
      4 and 10 years and academic achievement at 10 years. This developmental cascade
      applied equally to girls and boys and was independent of children's behavioral
      adjustment and social competence; mothers' supportive caregiving, verbal
      intelligence, education, and parenting knowledge; and the material home
      environment. Infants who were more motorically mature and who explored more
      actively at 5 months of age achieved higher academic levels as 14-year-olds. 

PMID- 23964002
TI  - Aggregation and cooperative effects in the aldol reactions of lithium enolates.
AB  - Density functional theory and Car-Parrinello molecular dynamics simulations have
      been carried out for model aldol reactions involving aggregates of lithium
      enolates derived from acetaldehyde and acetone. Formaldehyde and acetone have
      been used as electrophiles. It is found that the geometries of the enolate
      aggregates are in general determined by the most favorable arrangements of the
      point charges within the respective Lin On clusters. The reactivity of the
      enolates follows the sequence monomer?dimer>tetramer. In lithium aggregates, the
      initially formed aldol adducts must rearrange to form more stable structures in
      which the enolate and alkoxide oxygen atoms are within the respective Lin On
      clusters. Positive cooperative effects, similar to allosteric effects found in
      several proteins, are found for the successive aldol reactions in aggregates. The
      corresponding transition structures show in general sofa geometries. 

PMID- 23964003
TI  - [Transformation is necessary, transition is not].

PMID- 23964001
TI  - Electric field stimulation through a biodegradable polypyrrole-co
      polycaprolactone substrate enhances neural cell growth.
AB  - Nerve guidance conduits (NGCs) are FDA-approved devices used to bridge gaps
      across severed nerve cables and help direct axons sprouting from the proximal end
      toward the distal stump. In this article, we present the development of a novel
      electrically conductive, biodegradable NGC made from a polypyrrole-block
      polycaprolactone (PPy-PCL) copolymer material laminated with poly(lactic-co
      glycolic acid) (PLGA). The PPy-PCL has a bulk conductivity ranging 10-20 S/cm and
      loses 40 wt % after 7 months under physiologic conditions. Dorsal root ganglia
      (DRG) grown on flat PPy-PCL/PLGA material exposed to direct current electric
      fields (EF) of 100 mV/cm for 2 h increased axon growth by 13% (+/- 2%) toward
      either electrode of a 2-electrode setup, compared with control grown on identical
      substrates without EF exposure. Alternating current increased axon growth by 21%
      (+/-3%) without an observable directional preference, compared with the same
      control group. The results from this study demonstrate PLGA-coated PPy-PCL is a
      unique biodegradable material that can deliver substrate EF stimulation to
      improve axon growth for peripheral nerve repair.

PMID- 23964004
TI  - [Early alcohol initiation and increased adult alcohol consumption: cause or
      indicator?].
AB  - BACKGROUND: Early alcohol initiation is strongly associated with increased
      alcohol consumption and alcohol abuse/dependence in adulthood. The mechanisms
      that underlie this association are unclear. AIM: To examine whether there is a
      causal link between early alcohol initiation and later alcohol consumption.
      METHOD: Survey data were collected from twin pairs (age range 18-80) included in
      the Netherlands Twin Register (NTR). A discordant twin design was used to examine
      the origin of the link between early alcohol initiation and adult alcohol
      consumption. Within monozygotic pairs (82-143 pairs), twins who started drinking
      early were compared to their brother/sister who started drinking later, on
      frequency of alcohol use, weekly alcohol consumption, number of alcohol
      intoxications, excessive drinking, alcohol abuse/-dependence, and hazardous
      drinking. By drawing comparisons within monozygotic pairs, we were able to
      control for the effects of genes/shared environment. Additional analyses examined
      the effects of age, sex, and in-/exclusion of lifelong abstainers. RESULTS:
      Within monozygotic twin pairs, the twin who had started drinking early did not
      differ significantly from his/her brother/sister with respect to future alcohol
      consumption. Results were independent of age, sex, and in-/exclusion of lifelong
      abstainers. CONCLUSION: Early alcohol initiation did not have significant causal
      effects on subsequent alcohol consumption in adulthood and may be an indicator of
      a predisposition for alcohol consumption. Campaigns aimed at raising the minimum
      age for alcohol initiation will possibly have only a limited effect on adult
      alcohol consumption.

PMID- 23964006
TI  - [Psychiatry and brua].
AB  - BACKGROUND: Patients from Aruba, Bonaire and Curacao are often inclined to
      attribute mental problems to brua, the Dutch-Antillean counterpart of voodoo.
      Because little is known about brua and patients are usually reluctant to talk
      about it, problems can arise in the communication with biomedically trained
      health practitioners. AIM: To provide an overview of the literature on brua, and
      of the ways in which brua may interfere with the diagnosis and treatment of Dutch
      Antillean patients with mental health problems. METHOD: We searched the
      literature via PubMed and Embase (up to October 2012) and the historical
      literature (from 1880 onwards) written in Dutch, English, French, Spanish, and
      Papiamento. RESULTS: Brua has its origins in folk medicine and magico-religious
      rituals, which are regarded both as the cause of and a cure for mental illness.
      Although Antillean patients generally turn to medically trained professionals
      when they are confronted with medical problems, they often rely on brua medicine
      when they face either simpler problems, or problems for which Western medicine
      cannot provide a solution. CONCLUSION: On the basis of the literature, the area
      of tension between the Western approach to medicine and the brua approach seems
      to be insignificant, except perhaps in cases where hallucinogens or other psycho
      active substances complicate the clinical picture and in cases where the
      patient's fear for sorcery dominates clinical symptomatology.

PMID- 23964005
TI  - [A description of children and adolescents with somatic unexplained physical
      symptoms in a Dutch mental health care institution].
AB  - BACKGROUND: Medically unexplained symptoms (MUS) occur frequently in children and
      adolescents. Treatment of MUS in children and adolescents takes place mainly in
      mental health care (MHC) institutions, as does the treatment of adults with MUS.
      However, there is hardly any literature about the prevalence of MUS in children
      and adolescents in MHC. AIM: To study the prevalence of MUS in children and
      adolescents in Dutch MHC. METHOD: Comparisons were drawn between children and
      adolescents with MUS and those without MUS who had been referred to a Dutch MHC
      institution. RESULTS: Children and adolescents with MUS had more anxiety and
      depression and more introvert personality characteristics than children and
      adolescents without MUS. However, the quality of life of children and adolescents
      with MUS was similar to that of children and adolescents without MUS. CONCLUSION:
      One in five children and adolescents in Dutch MHC had MUS. These children and
      adolescents had introverted personality characteristics and showed anxious and
      depressed behavior, withdrawn-depressed behavior, and thought problems. The
      quality of life of children and adolescents with MUS and those without MUS was
      below average.

PMID- 23964007
TI  - [The practice of Dutch child and adolescent psychiatry - developments over the
      last fifteen years].
AB  - BACKGROUND: The child and adolescent psychiatry (cap) section of the Dutch
      Association for Psychiatry intends to keep track of the extent to which CAP is
      practised and to monitor the way in which it functions. The CAP has conducted
      three surveys since 1996. This paper reports on the 2012 survey. AIM: To
      investigate the composition (i.e. age and gender) of specialists working in child
      and adolescent psychiatry, to find out how much time these psychiatrists really
      spend on child and adolescent psychiatry and what type of work they actually do;
      furthermore, to make a list of specific questions such as 24-hour availability,
      and to note opinions regarding the planned transfer of child and adolescent
      mental health care facilities to town councils. METHOD: A survey was conducted
      and an analysis was made of the data collected. RESULTS: The number of
      specialists practicing child and adolescent psychiatry in the Netherlands,
      expressed in full-time equivalents, has more than doubled since 1996 (from 183 in
      1996 tot 389 in 2012). Compared to 1996, many more of these psychiatrists spend
      nearly all their time on CAP. The percentage of these specialists working only in
      private practice remains the same as in 1996 (19%) , although the percentage was
      lower in 2003 (135). Whereas in 1996 specialists in child and adolescent
      psychiatry worked mainly as psychotherapists, in 2012 they were working in a
      broader field, including assessment and pharmacotherapy. CONCLUSION: Dutch CAP
      has grown substantially over the past 15 years. Growth in psychiatry in general
      has been even more marked. Considering the current composition of the population,
      there is only a relatively limited amount of specialised psychiatric help
      available for people under the age of 20. The impending transfer of CAP mental
      health care facilities to town councils is a matter of deep concern to
      professionals and to psychiatrists in particular. Only if CAP investigations
      continue over the coming years will it become clear that this deep concern is
      entirely justified.

PMID- 23964008
TI  - [Resident old-age psychiatrists need training in the interpretation of cerebral
      imaging: a pituitary incidentaloma].
AB  - Due to the increased use of cerebral imaging with higher sensitivity, the old-age
      psychiatrist is more likely to find unexpected lesions. We report on a 73-year
      old man with schizoaffective disorder and increasing cognitive deterioration.
      When given a diagnostic MRI cerebrum a pituitary incidentaloma was found. An
      overview of the literature shows a high prevalence of pituitary incidentalomas.
      Complications are generally rare, but one should be alert. The old-age
      psychiatrist should take the lead in the assessment and interpretation of such
      imaging results. The relevant skills for this task should be developed in the
      field of old-age psychiatry during the residency training in psychiatry.

PMID- 23964009
TI  - [Why neuroimaging is important for old age psychiatry].

PMID- 23964010
TI  - [Manic-psychotic symptoms as clinical manifestation of hyperparathyroidism].
AB  - We discuss the case history of a woman aged 49 years who displayed manic
      psychotic symptoms as a clinical manifestation of hyperparathyroidism. Following
      resection of the parathyroid she developed severe depression. Primary
      hyperparathyroidism (PHPT) is characterised by an increase of the parathyroid
      hormone (PTH), which in turn leads to an increase in the plasma calcium. PHPT can
      be accompanied by various psychiatric symptoms ranging from personality changes
      and severe depression to obsessive-compulsive and paranoid symptoms.

PMID- 23964011
TI  - [Reaction on 'suicide: a medico-historical exploration'].

PMID- 23964014
TI  - Microscopic evaluation of vesicles shed by erythrocytes at elevated temperatures.
AB  - The images of human erythrocytes and vesicles were analyzed by a light microscopy
      system with spatial resolution of better than 90 nm. The samples were observed in
      an aqueous environment and required no freezing, dehydration, staining,
      shadowing, marking, or any other manipulation. Temperature elevation resulted in
      significant concentration increase of structurally transformed erythrocytes
      (echinocytes) and vesicles in the blood. The process of vesicle separation from
      spiculated erythrocytes was video recorded in real time. At a temperature of 37
      degrees C, mean vesicle concentrations and diameters were found to be 1.50 +/-
      0.35 * 10(6) vesicles per microliter and 0.365 +/- 0.065 MUm, respectively. The
      vesicle concentration increased approximately threefold as the temperature
      increased from 37 to 40 degrees C. It was estimated that 80% of all vesicles
      found in the blood are smaller than 0.4 MUm. Accurate account of vesicle numbers
      and dimensions suggest that 86% of the lost erythrocyte material is lost not by
      vesiculation but by another, as yet, unknown mechanism.

PMID- 23964013
TI  - Histones trigger sterile inflammation by activating the NLRP3 inflammasome.
AB  - Sterile cell death mediated inflammation is linked to several pathological
      disorders and involves danger recognition of intracellular molecules released by
      necrotic cells that activate different groups of innate pattern recognition
      receptors. Toll-like receptors directly interact with their extrinsic or
      intrinsic agonists and induce multiple proinflammatory mediators. In contrast,
      the NLRP3 inflammasome is rather thought to represent a downstream element
      integrating various indirect stimuli into proteolytic cleavage of interleukin
      (IL)-1beta and IL-18. Here, we report that histones released from necrotic cells
      induce IL-1beta secretion in an NLRP3-ASC-caspase-1-dependent manner. Genetic
      deletion of NLRP3 in mice significantly attenuated histone-induced IL-1beta
      production and neutrophil recruitment. Furthermore, necrotic cells induced
      neutrophil recruitment, which was significantly reduced by histone-neutralizing
      antibodies or depleting extracellular histones via enzymatic degradation. These
      results identify cytosolic uptake of necrotic cell-derived histones as a
      triggering mechanism of sterile inflammation, which involves NLRP3 inflammasome
      activation and IL-1beta secretion via oxidative stress. 

PMID- 23964012
TI  - Macrophage PPAR gamma Co-activator-1 alpha participates in repressing foam cell
      formation and atherosclerosis in response to conjugated linoleic acid.
AB  - Conjugated linoleic acid (CLA) has the unique property of inducing regression of
      pre-established murine atherosclerosis. Understanding the mechanism(s) involved
      may help identify endogenous pathways that reverse human atherosclerosis. Here,
      we provide evidence that CLA inhibits foam cell formation via regulation of the
      nuclear receptor coactivator, peroxisome proliferator-activated receptor (PPAR)
      gamma coactivator (PGC)-1alpha, and that macrophage PGC-1alpha plays a role in
      atheroprotection in vivo. PGC-1alpha was identified as a hub gene within a
      cluster in the aorta of the apoE(-/-) mouse in the CLA-induced regression model.
      PGC-1alpha was localized to macrophage/foam cells in the murine aorta where its
      expression was increased during CLA-induced regression. PGC-1alpha expression was
      also detected in macrophages in human atherosclerosis and was inversely linked to
      disease progression in patients with the disease. Deletion of PGC-1alpha in bone
      marrow derived macrophages promoted, whilst over expression of the gene inhibited
      foam cell formation. Importantly, macrophage specific deletion of PGC-1alpha
      accelerated atherosclerosis in the LDLR(-/-) mouse in vivo. These novel data
      support a functional role for PGC-1alpha in atheroprotection. 

PMID- 23964015
TI  - Where is the missing 40 MUg/d of vitamin D?

PMID- 23964016
TI  - Do whole grain cereals really reduce LDL-cholesterol by 0.72 mmol/L?

PMID- 23964017
TI  - Reply to Cannell.

PMID- 23964018
TI  - Does the cerebellum initiate movement?
AB  - Opinion is divided on what the exact function of the cerebellum is. Experiments
      are summarized that support the following views: (1) the cerebellum is a combiner
      of multiple movement factors; (2) it contains anatomically fixed permanent focal
      representation of individual body parts (muscles and segments) and movement modes
      (e.g., vestibular driven vs. cognitive driven); (3) it contains flexible changing
      representations/memory of physical properties of the body parts including muscle
      strength, segment inertia, joint viscosity, and segmental interaction torques
      (dynamics); (4) it contains mechanisms for learning and storage of the properties
      in item no. 3 through trial-and-error practice; (5) it provides for linkage of
      body parts, motor modes, and motordynamics via the parallel fiber system; (6) it
      combines and integrates the many factors so as to initiate coordinated movements
      of the many body parts; (7) it is thus enabled to play the unique role of
      initiating coordinated movements; and (8) this unique causative role is evidenced
      by the fact that: (a) electrical stimulation of the cerebellum can initiate
      compound coordinated movements; (b) in naturally initiated compound movements,
      cerebellar discharge precedes that in downstream target structures such as motor
      cerebral cortex; and (c) cerebellar ablation abolishes the natural production of
      compound movements in the awake alert individuals. 

PMID- 23964019
TI  - The association between maternal depression and anxiety during pregnancy and
      child attention problems may be partly explained by postnatal symptoms.

PMID- 23964020
TI  - Kinesin spindle protein (KSP) inhibitors in combination with chemotherapeutic
      agents for cancer therapy.
AB  - A diverse group of proteins, the activities of which are precisely orchestrated
      during mitosis, have emerged as targets for cancer therapeutics; these include
      the Aurora kinases (AKs), Polo-like kinases (PLKs), and the kinesin spindle
      protein (KSP). KSP is essential for the proper separation of spindle poles during
      mitosis. Agents that target KSP selectively act on cells undergoing cell
      division, which means that KSP inhibitors are mitosis-specific drugs, and have
      demonstrated remarkable activities in vitro. However, a significant obstacle to
      the success of KSP inhibitors is that these compounds, with tremendous efficacy
      in vitro, have demonstrated little or even no antitumor activity in vivo.
      Accumulated data suggest that a combination of KSP inhibitors with various
      cytostatic drugs will result in a more powerful tumor-killing effect than
      monotherapy. Combination therapies might predominate and represent the next
      frontier in the discovery research of KSP inhibitors as potential anticancer
      drugs. Few published studies have reviewed combination therapy using KSP
      inhibitors. Herein we provide a comprehensive review of the literature on KSP
      inhibitor monotherapy and therapeutic combinations. The current state and
      problems are also discussed. 

PMID- 23964021
TI  - A new layered photocathode with porous NiO nanosheets: an effective candidate for
      p-type dye-sensitized solar cells.
AB  - Herein, with the purpose of improving the efficiency of p-type dye-sensitized
      solar cells (DSSCs), a new layered photocathode (LP) is fabricated from irregular
      overlapping wrinkled porous NiO nanosheets. The LP was sensitized by using a
      commonly used dye, coumarin 343(C343), and then assembled into p-type DSSCs
      through coupling with a platinum photoanode. Photoelectochemical characterization
      showed that the LP cell exhibited a clearly enhanced power-conversion efficiency
      (by a factor of 4) compared with a cell with a NiO-nanoparticle photocathode
      (NP). This excellent performance could be attributed to the overlapping layered
      structure, which favored hole transport, as confirmed by electrochemical
      impedance spectroscopy, and to the large surface area of the porous NiO
      nanosheets, which were favorable for dye adsorption. 

PMID- 23964022
TI  - Molecular diversity subdivides the adult forebrain neural stem cell population.
AB  - Neural stem cells (NSCs) in the ventricular domain of the subventricular zone (V
      SVZ) of rodents produce neurons throughout life while those in humans become
      largely inactive or may be lost during infancy. Most adult NSCs are quiescent,
      express glial markers, and depend on Notch signaling for their self-renewal and
      the generation of neurons. Using genetic markers and lineage tracing, we
      identified subpopulations of adult V-SVZ NSCs (type 1, 2, and 3) indicating a
      striking heterogeneity including activated, brain lipid binding protein (BLBP,
      FABP7) expressing stem cells. BLBP(+) NSCs are mitotically active components of
      pinwheel structures in the lateral ventricle walls and persistently generate
      neurons in adulthood. BLBP(+) NSCs express epidermal growth factor (EGF)
      receptor, proliferate in response to EGF, and are a major clonogenic population
      in the SVZ. We also find BLBP expressed by proliferative ventricular and
      subventricular progenitors in the fetal and postnatal human brain. Loss of
      BLBP(+) stem/progenitor cells correlates with reduced neurogenesis in aging
      rodents and postnatal humans. These findings of molecular heterogeneity and
      proliferative differences subdivide the NSC population and have implications for
      neurogenesis in the forebrain of mammals during aging.

PMID- 23964023
TI  - Genetic and genomic analyses of musculoskeletal differences between BEH and BEL
      strains.
AB  - Berlin high (BEH) and Berlin low (BEL) strains selected for divergent growth
      differ threefold in body weight. We aimed at examining muscle mass, which is a
      major contributor to body weight, by exploring morphological characteristics of
      the soleus muscle (fiber number and cross sectional area; CSA), by analyzing the
      transcriptome of the gastrocnemius and by initiating quantitative trait locus
      (QTL) mapping. BEH muscles were four to eight times larger than those of BEL. In
      substrain BEH+/+, mutant myostatin was replaced with a wild-type allele; however,
      BEH+/+muscles still were two to four times larger compared with BEL. BEH soleus
      muscle fibers were two times more numerous (P < 0.0001) and CSA was two times
      larger (P < 0.0001) compared with BEL. In addition, soleus femoral attachment
      anomaly (SFAA) was observed in all BEL mice. One significant (Chr 1) and four
      suggestive (Chr 3, 4, 6, and 9) muscle weight QTLs were mapped in a 21-day-old F2
      intercross (n = 296) between BEH and BEL strains. The frequency of SFAA incidence
      in the F2 and in the backcross to BEL strain (BCL) suggested the presence of more
      than one causative gene. Two suggestive SFAA QTLs were mapped in BCL; however,
      their peak markers were not associated with the phenotype in F2. RNA-Seq analysis
      revealed 2,148 differentially expressed (P < 0.1) genes and 45,673 single
      nucleotide polymorphisms and >2,000 indels between BEH+/+ and BEL males. In
      conclusion, contrasting muscle traits and genomic and gene expression differences
      between BEH and BEL strains provide a promising model for the search for genes
      involved in muscle growth and musculoskeletal morphogenesis. 

PMID- 23964024
TI  - Acute and potentially persistent effects of scuba diving on the blood
      transcriptome of experienced divers.
AB  - During scuba diving, the circulatory system is stressed by an elevated partial
      pressure of oxygen while the diver is submerged and by decompression-induced gas
      bubbles on ascent to the surface. This diving-induced stress may trigger
      decompression illness, but the majority of dives are asymptomatic. In this study
      we have mapped divers' blood transcriptomes with the aim of identifying genes,
      biological pathways, and cell types perturbed by the physiological stress in
      asymptomatic scuba diving. Ten experienced divers abstained from diving for >2 wk
      before performing a 3-day series of daily dives to 18 m depth for 47 min while
      breathing compressed air. Blood for microarray analysis was collected before and
      immediately after the first and last dives, and 10 matched nondivers provided
      controls for predive stationary transcriptomes. MetaCore GeneGo analysis of the
      predive samples identified stationary upregulation of genes associated with
      apoptosis, inflammation, and innate immune responses in the divers, most
      significantly involving genes in the TNFR1 pathway of caspase-dependent
      apoptosis, HSP60/HSP70 signaling via TLR4, and NF-kappaB-mediated transcription.
      Diving caused pronounced shifts in transcription patterns characteristic of
      specific leukocytes, with downregulation of genes expressed by CD8+ T lymphocytes
      and NK cells and upregulation of genes expressed by neutrophils, monocytes, and
      macrophages. Antioxidant genes were upregulated. Similar transient responses were
      observed after the first and last dive. The results indicate that sublethal
      oxidative stress elicits the myeloid innate immune system in scuba diving and
      that extensive diving may cause persistent change in pathways controlling
      apoptosis, inflammation, and innate immune responses. 

PMID- 23964025
TI  - Conformational changes represent the rate-limiting step in the transport cycle of
      maize sucrose transporter1.
AB  - Proton-driven Suc transporters allow phloem cells of higher plants to accumulate
      Suc to more than 1 M, which is up to ~1000-fold higher than in the surrounding
      extracellular space. The carrier protein can accomplish this task only because
      proton and Suc transport are tightly coupled. This study provides insights into
      this coupling by resolving the first step in the transport cycle of the Suc
      transporter SUT1 from maize (Zea mays). Voltage clamp fluorometry measurements
      combining electrophysiological techniques with fluorescence-based methods enable
      the visualization of conformational changes of SUT1 expressed in Xenopus laevis
      oocytes. Using the Suc derivate sucralose, binding of which hinders
      conformational changes of SUT1, the association of protons to the carrier could
      be dissected from transport-associated movements of the protein. These combined
      approaches enabled us to resolve the binding of protons to the carrier and its
      interrelationship with the alternating movement of the protein. The data indicate
      that the rate-limiting step of the reaction cycle is determined by the
      accessibility of the proton binding site. This, in turn, is determined by the
      conformational change of the SUT1 protein, alternately exposing the binding
      pockets to the inward and to the outward face of the membrane.

PMID- 23964027
TI  - Successful retrograde recanalization of chronic total coronary occlusion with
      multiple bioresorbable vascular scaffolds ('full polymer jacket'): initial
      experience and rationale.

PMID- 23964028
TI  - Pathological insights of a woven coronary artery with optical coherence
      tomography.

PMID- 23964026
TI  - The Arabidopsis metacaspase9 degradome.
AB  - Metacaspases are distant relatives of the metazoan caspases, found in plants,
      fungi, and protists. However, in contrast with caspases, information about the
      physiological substrates of metacaspases is still scarce. By means of N-terminal
      combined fractional diagonal chromatography, the physiological substrates of
      metacaspase9 (MC9; AT5G04200) were identified in young seedlings of Arabidopsis
      thaliana on the proteome-wide level, providing additional insight into MC9
      cleavage specificity and revealing a previously unknown preference for acidic
      residues at the substrate prime site position P1'. The functionalities of the
      identified MC9 substrates hinted at metacaspase functions other than those
      related to cell death. These results allowed us to resolve the substrate
      specificity of MC9 in more detail and indicated that the activity of
      phosphoenolpyruvate carboxykinase 1 (AT4G37870), a key enzyme in gluconeogenesis,
      is enhanced upon MC9-dependent proteolysis.

PMID- 23964029
TI  - Alcohol septal ablation with septal myocardial isolation using the double-balloon
      method for refractory hypertrophic obstructive cardiomyopathy.

PMID- 23964030
TI  - Endovascular treatment of inoperable acute type A dissection via the transapical
      approach.

PMID- 23964031
TI  - Belts, braces, and pacemaker erosion.

PMID- 23964032
TI  - Optimal medical therapy vs. revascularization on long-term LV function.

PMID- 23964034
TI  - Subacute sclerosing panencephalitis presenting as acute disseminated
      encephalomyelitis and pseudotumour cerebri.
AB  - Subacute sclerosing panencephalitis (SSPE) is a chronic progressive encephalitis
      of childhood and young adults due to persistent measles virus infection. The
      usual age of onset is between 5 and 15 years. There are wide varieties of
      presentations of SSPE described in the literatures. Variable clinical
      presentations may lead to diagnostic dilemma and unnecessary investigations
      especially in developing countries, where the measles is quite endemic and
      vaccination status is not up to the mark because of poor literacy and
      socioeconomic status. Good clinical correlations, neuroimaging findings, EEG and
      cerebrospinal fluid (CSF) marker for SSPE yield the clue to diagnosis. This case
      illustrates a 13-year-old boy presented with short history of intellectual
      decline, headache, papilloedema, cranial nerve palsy, myoclonus with suggestive
      neuroimaging mimicking acute disseminated encephalomyelitis (ADEM) and
      pseudotumour cerebri. Subsequently he was diagnosed to be a case of SSPE on the
      basis of CSF and serum measles antibody titer.

PMID- 23964033
TI  - Long-term outcomes and cardiac surgery in critically ill patients with infective
      endocarditis.
AB  - AIMS: To assess long-term outcomes and the management of critical left-sided
      infective endocarditis (IE) and evaluate the impact of surgery. METHODS AND
      RESULTS: Among the 198 patients included prospectively for IE across 33 adult
      intensive care units (ICU) in France from 1 April 2007 to 1 October 2008, 137
      (69%) were dead at a median follow-up time of 59.5 months. Characteristics
      significantly associated with mortality were: Sepsis-related Organ-Failure
      Assessment (SOFA) score at ICU admission [Hazard ratio (HR), 95% Confidence
      Interval (CI) of 1.43 (0.79-2.59) for SOFA 5-9; 2.01 (1.05-3.85) for SOFA 10-14;
      3.53 (1.75-7.11) for SOFA 15-20; reference category SOFA 0-4; P = 0.003];
      prosthetic mechanical valve IE [HR 2.01; 95% CI 1.09-3.69, P = 0.025]; vegetation
      size >=15 mm [HR 1.64; 95% CI 1.03-2.63, P = 0.038]; and cardiac surgery [HR
      (95%CI), 0.33 (0.16-0.67) for surgery <=1 day after IE diagnosis; 0.61 (0.29
      1.26) for surgery 2-7 days after IE diagnosis; 0.42 (0.21-0.83) for surgery >7
      days after IE diagnosis; reference category no surgery; P = 0.005]. One hundred
      and three (52%) patients underwent cardiac surgery after a median time of 6 (16)
      days. Independent predictors of surgical intervention on multivariate analysis
      were: age <=60 years [Odds ratio (OR) 5.30; 95% CI (2.46-11.41), P < 0.01], heart
      failure [OR 3.27; 95% CI (1.03-10.35), P = 0.04], cardiogenic shock [OR 3.31; 95%
      CI (1.47-7.46), P = 0.004], septic shock [OR 0.25; 95% CI (0.11-0.59), P =
      0.002], immunosuppression [OR 0.15; 95% CI (0.04-0.55), P = 0.004], and diagnosis
      before or within 24 h of ICU admission [OR 2.81; 95% CI (1.14-6.95), P = 0.025].
      SOFA score calculated the day of surgery was the only independently associated
      factor with long-term mortality [HR (95% CI) 1.59 (0.77-3.28) for SOFA 5-9; 3.56
      (1.71-7.38) for SOFA 10-14; 11.58 (4.02-33.35) for SOFA 15-20; reference category
      SOFA 0-4; P < 0.0001]. Surgical timing was not associated with post-operative
      outcomes. Of the 158 patients with a theoretical indication for surgery, the 58
      deemed not fit had a 95% mortality rate. CONCLUSION: Mortality in patients with
      critical IE remains unacceptably high. Factors associated with long-term outcomes
      are the severity of multiorgan failure, prosthetic mechanical valve IE,
      vegetation size >=15 mm, and surgical treatment. Up to one-third of potential
      candidates do not undergo surgery and these patients experience extremely high
      mortality rates. The strongest independent predictor of post-operative mortality
      is the pre-operative multiorgan failure score while surgical timing does not seem
      to impact on outcomes.

PMID- 23964035
TI  - Hypereosinophilic syndrome secondary to strongyloides infection: a case of
      recurrent asthma exacerbations.
AB  - Hypereosinophilic syndrome is a disease characterised by a persistently elevated
      eosinophil count. The syndrome can be reactive to infections, autoimmune disease,
      cancers, etc. Multiple organ involvement can occur including cardiomyopathies,
      pulmonary involvement and neuropathies. We describe a case of a patient who
      presented with signs and symptoms of asthma with recurrent asthma exacerbations,
      but in fact proved to be hypereosinophilic syndrome secondary to strongyloides
      infection.

PMID- 23964036
TI  - Coinfection of pulmonary mucormycosis and aspergillosis presenting as bilateral
      vocal cord palsy.
AB  - Invasive pulmonary coinfection with Mucor and Aspergillus is rare. Bilateral
      vocal cord paralysis resulting from coinfection with these two fungi to our
      knowledge has not been reported in the literature. We report a young woman with
      diabetes who presented with symptoms of community acquired pneumonia in
      association with hoarseness of voice. Investigations revealed air space
      consolidation of the right upper lobe, evidence of mediastinal involvement
      extending into the paratracheal space and entrapment of right upper lobe
      pulmonary artery. Bronchoscopy revealed bilateral vocal cord paralysis and
      sloughing of mucosa of the right upper lobe bronchus and the bronchus
      intermedius. Microbiological and pathological results confirmed Mucor and
      Aspergillus. Extensive vascular and mediastinal involvement precludes surgical
      debridement. Despite aggressive medical management the patient deteriorated and
      died of respiratory failure. Strong suspicion of invasive fungal infections in
      immune compromised patients presenting with unresolving pneumonia and hoarseness
      of voice, early aggressive treatment is crucial for the patient survival.

PMID- 23964037
TI  - Acute respiratory failure secondary to mesalamine-induced interstitial
      pneumonitis.
AB  - Interstitial pneumonitis as an adverse effect of mesalamine therapy is a rare but
      potentially serious complication. Patients typically have a mild disease course
      with no documented cases of respiratory failure in published literature. Given
      its variable latent period and non-specific signs and symptoms, it may be
      difficult to diagnose. We present the case of a 65-year-old man who presented
      with symptoms of fever, shortness of breath and a non-productive cough, 2 weeks
      after initiation of therapy with mesalamine. His hospital course was complicated
      by acute respiratory failure requiring intubation and mechanical ventilation.
      Radiographic studies revealed bilateral lower lobe infiltrates and bronchosopy
      with bronchoalveolar lavage and transbronchial biopsy were consistent with a
      diagnosis of drug-induced interstitial pneumonitis. The aim of this paper is to
      highlight the importance of considering a diagnosis of mesalamine-induced lung
      injury in patients presenting with respiratory symptoms while on mesalamine
      therapy and to review relevant literature.

PMID- 23964039
TI  - The pericallosal lipoma mimicking deep cerebral vein thrombus.

PMID- 23964038
TI  - Clarithromycin-induced haemorrhagic colitis.
AB  - Haemorrhagic colitis by Klebsiella oxytoca has been described as an antibiotic
      associated colitis, particularly with the use of ampicillin. Here we report a
      patient with haemorrhagic colitis caused by K oxytoca after the use of
      clarithromycin. A 67-year-old Japanese woman with diabetes presented with
      mucobloody diarrhoea and abdominal pain. Stool culture grew K oxytoca.
      Colonoscopy showed the appearance of haemorrhagic colitis. Further history taking
      revealed that she had received a course of oral clarithromycin for upper
      respiratory tract infection. She had recovered by conservative treatment. We
      should be careful about gastrointestinal symptoms in patients on clarithromycin,
      which can cause haemorrhagic colitis associated with K oxytoca.

PMID- 23964040
TI  - Multiple haemangiomas, diaphragmatic eventration and Beckwith-Wiedemann syndrome:
      an unusual association.
AB  - A 6-month-old girl with Beckwith-Wiedemann syndrome, multiple haemangiomas
      (axillary, laryngeal, pulmonary and hepatic) and diaphragmatic eventration was
      reported. All tumours responded to treatment with propranolol. The surgical
      correction of diaphragmatic eventration was crucial to a better outcome.

PMID- 23964041
TI  - Sphenoidal sinus mucocele presenting with acute visual loss in a scuba diver.
AB  - A 43-year-old male scuba diver presented with an acute history of painful
      unilateral visual loss after scuba diving. He had right-sided retrobulbar pain
      and headache. He was known to have sinusitis and had transient visual loss in two
      previous episodes after scuba diving. His visual acuity was hand motions and
      20/20 in the right and left eye, respectively. There was no proptosis. He had a
      right relative afferent pupillary defect. Colour vision was normal in the left
      eye and absent in the right eye. Fundal examination revealed healthy discs and
      macula bilaterally. He was assessed as a right optic neuropathy, possibly
      secondary to compression. An MRI of the brain revealed a large sphenoidal
      mucocele extending into the right optic foramen. He was treated with oral
      steroids, antibiotics and nasal decongestants. He underwent endoscopic intranasal
      sphenoidectomy and marsupialisation with return of his visual acuity to 20/25 in
      that eye.

PMID- 23964042
TI  - Penile fracture with urethral injury: evaluation by contrast imaging.

PMID- 23964043
TI  - Bilateral transverse sinus stenosis causing intracranial hypertension.
AB  - Idiopathic intracranial hypertension (IIH) has been associated with transverse
      sinus stenosis in a number of cases. Some authors advocate for stent placement
      when transverse sinus stenosis is responsible for pseudotumor symptoms. A 19-year
      old man with IIH, bilateral transverse sinus stenosis was apparent on a CT
      venography, with reconstitution of the lateral sinus. MRI was then performed, and
      transverse sinus stenosis was confirmed. An impressive network of dilated
      collateral veins became apparent on VENBOLD sequences. Treatment options in this
      case include cerebrospinal fluid (CSF) shunting, optic nerve fenestrations and
      transverse sinus stenting. A ventriculoperitoneal shunt was placed in this
      patient, with prompt resolution of pseudotumor symptoms.

PMID- 23964044
TI  - Intraprocedural parenchymal blood volume as a marker of reperfusion status in
      acute ischemic stroke intervention.
AB  - Parenchymal blood volume (PBV) mapping with flat panel detectors may provide real
      time estimates of tissue perfusion during endovascular ischemic stroke
      procedures. We present two cases of acute middle cerebral artery (MCA) occlusion
      to demonstrate how PBV may: (1) be used in acute stroke; (2) influence
      intraprocedural decision-making; and (3) potentially serve as a predicator of
      clinical outcome. Both cases were successfully recanalized with endovascular
      embolectomy. Intraprocedural PBV maps were obtained immediately before and after
      recanalization. Pre-intervention reductions in PBV were seen throughout the MCA
      territory in both cases, with significant improvement in PBV in one case with
      good radiographic and clinical outcome and a lack of improvement in PBV in the
      second case with a large infarct volume. PBV deficit normalization may occur with
      recanalization of the parent artery and probably represents successful
      reperfusion. Baseline PBV maps should therefore be interpreted with caution and
      not interpreted to represent irreversible core infarct.

PMID- 23964045
TI  - Congenital diaphragmatic hernia associated with oesophageal atresia and tracheo
      oesophageal fistula in a low birth weight infant.
AB  - The cooccurrence of congenital diaphragmatic hernia and oesophageal atresia with
      distal tracheo-oesophageal fistula is very rare and carries high mortality. Very
      few anecdotal case reports and one case series have been reported in the
      literature. We report a case of a late preterm, low birth weight infant with this
      rare association who was successfully managed by staged surgical approach and had
      good outcome.

PMID- 23964046
TI  - Unusual delayed presentation of head trauma complicating outcome of facial nerve
      decompression surgery.
AB  - Late presentation of head trauma is rare. A young boy presented with a traumatic
      facial paralysis after head trauma. A CT scan of the head showed temporal bone
      fracture without intracranial insult. Facial nerve decompression was performed
      and paralysis started improving. However, he presented with vertigo and
      sensorineural hearing loss after 2 months. Clinical examination also showed
      cerebellar sign. We suspected iatrogenic injury to the cochlea; however, brain
      MRI showed haemorrhage in the area of anterior inferior cerebellar artery. The
      patient was managed conservatively and the vertigo improved. This case stresses
      on unusual late presentation of head trauma and cerebellar artery injury that
      complicated the outcome of facial nerve paralysis.

PMID- 23964047
TI  - A giant spinal arterial aneurysm in a child presenting as quadriparesis.
AB  - A giant spinal aneurysm from anterior spinal artery not associated with
      arteriovenous (AV) malformations is unusual and no such cases have been reported
      in children. Few cases have been described as part of AV malformation complex and
      coarctation of the aorta. We report a case of anterior spinal aneurysm in a 1
      year-old girl causing a subarachnoid haemorrhage and a cervical cord lesion. The
      diagnosis was confirmed with a multislice CT angiography. A microsurgical
      decompression was performed and excision of aneurysm was unsuccessful but
      neurological deficits were improved. No further approach was accepted by the
      parents. The mechanism for the development of spinal isolated aneurysms is not
      clear; it can be related to congenital vessel abnormalities and genetic origin.
      The multislice CT angiography is a very useful method to demonstrate the features
      of this entity. Previous reports of isolated spinal aneurysm are reviewed.

PMID- 23964048
TI  - Lung abscess complicating pneumococcal pneumonia: a causal role of non-steroidal
      anti-inflammatory drugs?
AB  - Pulmonary abscess is a distinctly uncommon complication of pneumococcal pneumonia
      in immunocompetent adults that has recently been reported to occur following
      administration of non-steroidal anti-inflammatory drugs (NSAIDs). We report
      herein the case of a 24-year-old patient with no predisposing risk factor who
      developed a lung abscess after NSAIDs exposure, further illustrating this
      potentially severe complication of NSAIDs use, especially in the absence of
      associated antibiotic therapy.

PMID- 23964049
TI  - Novel psychoactive substances: a novel clinical challenge.
AB  - The recreational use of novel psychoactive substances in the UK has increased
      markedly within the last decade. The variety of new substances synthesised and
      sold as 'legal', often under the pretence of being 'plant food' or 'bath salts'
      is similarly increasing. This presents challenges to clinicians: they may be
      unaware of these substances or unable to identify them and their potential for
      complications and drug interactions. This case describes a patient who ingested a
      novel psychoactive substance and presented with severe agitation following a
      delay of several days. He experienced renal, hepatic and neurological
      complications requiring critical care input. Our case adds to the current
      repertoire of knowledge regarding the effects of ingestion of novel cathinones.

PMID- 23964050
TI  - Fusobacterium necrophorum: a rare cause of hepatic abscess in an immunocompetent
      individual.
AB  - In the present case a 30-year-old African American man was admitted with fever
      and chills secondary to two large hepatic abscesses diagnosed on an ultrasound.
      The patient was started on antibiotics after blood cultures were drawn. Initially
      the abscess was drained and showed dramatic improvement upon repeat imaging. The
      blood cultures revealed Gram-negative rods that were identified as Fusobacterium
      necrophorum. At that time the patient was switched to levofloxacin and
      metronidazole based on sensitivities. On this new antibiotic regime the patient
      improved dramatically. After just 5 days the patient was discharged home on oral
      antibiotics and was scheduled to follow-up in 1 week. In the present case we
      present a healthy 30-year-old man with no significant co-morbidities who
      developed a hepatic abscess from F necrophorum but successfully recovered after
      appropriate antibiotic treatment.

PMID- 23964051
TI  - Malrotation with transverse colon volvulus in early pregnancy: a rare cause for
      acute intestinal obstruction.
AB  - Colonic volvulus is a relatively uncommon cause of large bowel obstruction,
      accounting for 10% of colonic obstructions. Volvulus of the transverse colon is
      quite rare, accounting for only 4-11% of all reported cases. We report an unusual
      case of documented volvulus of the transverse colon in a pregnant woman with
      intestinal malrotation and concomitant acute intestinal obstruction by congenital
      bands and adhesions.

PMID- 23964052
TI  - Laparoscopic management of Peutz-Jeghers syndrome (PJS) presenting with chronic
      non-ischaemic jejuno-jejunal intussusception in an adolescent girl.

PMID- 23964053
TI  - Uraemic lung in severe azotaemia.

PMID- 23964054
TI  - SFAs do not impair endothelial function and arterial stiffness.
AB  - BACKGROUND: It is uncertain whether saturated fatty acids (SFAs) impair
      endothelial function and contribute to arterial stiffening. OBJECTIVE: We tested
      the effects of replacing SFAs with monounsaturated fatty acids (MUFAs) or
      carbohydrates on endothelial function and arterial stiffness. DESIGN: With the
      use of a parallel-designed randomized controlled trial in 121 insulin-resistant
      men and women, we measured vascular function after 1 mo of consumption of a high
      SFA (HS) diet and after 24 wk after random assignment to the HS diet or diets
      that contained <10% SFAs and were high in either MUFAs or carbohydrates. The
      primary outcome was a change in flow-mediated dilation (FMD), and secondary
      outcomes were changes in carotid to femoral pulse wave velocity (PWV) and plasma
      8-isoprostane F2alpha-III concentrations. RESULTS: For 112 participants with data
      available for analysis on the specified outcomes, no significant differences were
      shown. FMD with the HS reference diet was 6.7 +/- 2.2%, and changes (95% CIs)
      after 6 mo of intervention were +0.3 (-0.4, 1.1), -0.2 (-0.8, 0.5), and -0.1 (
      0.6, 0.7) with HS, high-MUFA (HM), and high-carbohydrate (HC) diets,
      respectively. After consumption of the HS reference diet, the geometric mean (+/
      SD) PWV was 7.67 +/- 1.62 m/s, and mean percentages of changes (95% CIs) were 
      1.0 (-6.2, 4.3) with the HS diet, 2.7 (-1.4, 6.9) with the HM diet, and -1.0 (
      5.5, 3.4) with the HC diet. With the HS reference diet, the geometric mean (+/
      SD) plasma 8-isoprostane F2alpha-III concentration was 176 +/- 85 pmol/L, and
      mean percentage of changes (95% CIs) were 1 (-12, 14) with the HS diet, 6 (-5,
      16) with the HM diet, and 4 (-7, 16) with the HC diet. CONCLUSION: The
      replacement of SFAs with MUFAs or carbohydrates in healthy subjects does not
      affect vascular function. This trial was registered at Current Controlled Trials
      (http://www.controlled-trials.com/ISRCTN) as ISRCTN 29111298.

PMID- 23964056
TI  - Critical windows for nutritional interventions against stunting.

PMID- 23964055
TI  - A diet rich in high-glucoraphanin broccoli interacts with genotype to reduce
      discordance in plasma metabolite profiles by modulating mitochondrial function.
AB  - BACKGROUND: Observational and experimental studies suggest that diets rich in
      cruciferous vegetables and glucosinolates may reduce the risk of cancer and
      cardiovascular disease (CVD). OBJECTIVE: We tested the hypothesis that a 12-wk
      dietary intervention with high-glucoraphanin (HG) broccoli would modify
      biomarkers of CVD risk and plasma metabolite profiles to a greater extent than
      interventions with standard broccoli or peas. DESIGN: Subjects were randomly
      assigned to consume 400 g standard broccoli, 400 g HG broccoli, or 400 g peas
      each week for 12 wk, with no other dietary restrictions. Biomarkers of CVD risk
      and 347 plasma metabolites were quantified before and after the intervention.
      RESULTS: No significant differences in the effects of the diets on biomarkers of
      CVD risk were found. Multivariate analyses of plasma metabolites identified 2
      discrete phenotypic responses to diet in individuals within the HG broccoli arm,
      differentiated by single nucleotide polymorphisms associated with the PAPOLG
      gene. Univariate analysis showed effects of sex (P < 0.001), PAPOLG genotype (P <
      0.001), and PAPOLG genotype * diet (P < 0.001) on the plasma metabolic profile.
      In the HG broccoli arm, the consequence of the intervention was to reduce
      variation in lipid and amino acid metabolites, tricarboxylic acid (TCA) cycle
      intermediates, and acylcarnitines between the 2 PAPOLG genotypes. CONCLUSIONS:
      The metabolic changes observed with the HG broccoli diet are consistent with a
      rebalancing of anaplerotic and cataplerotic reactions and enhanced integration of
      fatty acid beta-oxidation with TCA cycle activity. These modifications may
      contribute to the reduction in cancer risk associated with diets that are rich in
      cruciferous vegetables. This trial was registered at clinicaltrials.gov as
      NCT01114399.

PMID- 23964057
TI  - Antihypertensive medication and the effects of black tea on blood pressure
      variation.

PMID- 23964059
TI  - Vaccine perceptions among Oregon health care providers.
AB  - Health care providers exert a significant influence on parental pediatric
      vaccination decisions. We conducted hour-long interviews with traditional and
      alternative health care providers in which we explored a range of associations
      between vaccination perceptions and practice. A key finding was that the Health
      Belief Model constructs of perceived susceptibility to and severity of either an
      illness or an adverse vaccine event partially explained health care provider
      (HCP) beliefs about the risks or benefits of vaccination, especially among
      alternative care providers. Low or high perceived susceptibility to a vaccine
      preventable disease (VPD) or of the severity of a given VPD affects whether an
      HCP will promote or oppose pediatric vaccination recommendations. Beyond these
      perceptions, health and vaccination beliefs are affected by the contextual
      factors of personal experience, group norms, immunology beliefs, and beliefs
      about industry and government. Building powerful affective heuristics might be
      critical to balancing the forces that defeat good public health practices. 

PMID- 23964060
TI  - Metasynthesis and bricolage: an artistic exercise of creating a collage of
      meaning.
AB  - During the past decades, new approaches to synthesizing qualitative data have
      been developed. However, this methodology continues to face significant
      philosophical and practical challenges. By reviewing the literature on this
      topic, our overall aim in this article is to explore the systematic and creative
      research processes involved in the act of metasynthesizing. By investigating
      synthesizing processes borrowed from two studies, we discuss matters of
      transparency and transferability in relation to how multiple qualitative studies
      are interpreted and transformed into one narrative. We propose concepts such as
      bricolage, metaphor, playfulness, and abduction as ideas that might enhance
      understanding of the importance of combinations of scientific and artistic
      approaches to the way the synthesizer "puzzles together" an interpretive account
      of qualitative studies. This study can benefit researchers by increasing their
      awareness of the artistic processes involved in qualitative analysis and
      metasynthesis to expand the domain and methods of their fields. 

PMID- 23964061
TI  - Central aortic blood pressure of hypertensive men during short-term cold
      exposure.
AB  - BACKGROUND: Short- and long-term exposures to cold increase blood pressure and
      may explain the higher wintertime cardiovascular morbidity and mortality.
      Hypertensive subjects may be more susceptible to adverse cold-related
      cardiovascular health effects. The aim of our study was to assess the effect of
      short-term cold exposure on central aortic blood pressure among untreated
      hypertensive men. METHODS: We conducted a population-based recruitment of 41
      hypertensive men and a control group of 20 men without hypertension (aged 55-65
      years) who underwent whole-body cold exposure (15-minute exposure to temperature 
      10  degrees C, wind 3 m/s, winter clothes). Central aortic blood pressure,
      augmentation index, and subendocardial viability ratio were measured by radial
      artery applanation tonometry. RESULTS: Short-term cold exposure increased the
      central aortic blood pressure similarly both in both hypertensive men, from
      130/93 to 162/107 mm Hg (P < 0.001) and men in the control group, from 114/81 to
      142/91 mmHg (P < 0.001). Augmentation index increased by 12% (from 10% to 22%, P
      < 0.001; and from 16% to 28%, P < 0.001, respectively), whereas subendocardial
      viability ratio decreased 10% (from 188% to 177%, P = 0.001; and from 203% to
      193%, P = 0.01, respectively) during cold exposure in both hypertensive men and
      control subjects. CONCLUSIONS: Short-term cold exposure increases central aortic
      blood pressure and cardiac workload, and myocardial oxygen demand slightly
      increases in relation to blood supply in untreated hypertensive middle-aged men.
      Because of the higher baseline blood pressure among hypertensive subjects, the
      cold-induced rise in central aortic blood pressure may increase the risk of
      adverse cardiovascular health effects.

PMID- 23964062
TI  - Is the interpretation of rapid antigen testing for respiratory syncytial virus as
      simple as positive or negative?
AB  - OBJECTIVE: To measure the performance characteristics of an immunochromatographic
      rapid antigen test for respiratory syncytial virus (RSV) and determine how its
      interpretation should be contextualised in patients presenting to the emergency
      department (ED) with bronchiolitis. DESIGN: Diagnostic accuracy study of a rapid
      RSV test. SETTING: County hospital ED. INTERVENTION: We took paired nasal samples
      from consecutively enrolled infants with bronchiolitis and tested them with a
      rapid immunochromatographic antigen test and reverse transcriptase PCR gold
      standard. OUTCOME MEASURES: Sensitivity, specificity, the effect of point
      prevalence, clinical findings and overall context on predictive values. We used
      these to construct a graphical contextual model to show how the results of RSV
      antigen tests from infants presenting within 24 h should influence interpretation
      of subsequent antigen tests. RESULTS: We analysed 607 patients. The sensitivity
      and specificity for immunochromatographic testing was 79.4% (95% CI 73.9% to
      84.2%) and 67.1% (95% CI 61.9% to 72%) respectively. We found little evidence of
      spectrum bias. In our contextual model the best predictor of a positive RT-PCR
      test was a positive antigen test OR 5.47 (95% CI 3.65 to 8.18) and the number of
      other infants having positive tests within 24 h OR 1.48 (95% CI 1.26 to 1.72) per
      infant. Increasing numbers presenting to the ED with bronchiolitis in a given day
      increases the probability of RSV infection. CONCLUSIONS: The RSV antigen test we
      examined had modest performance characteristics. The results of the antigen test
      should be interpreted in the context of the results of previous tests.

PMID- 23964063
TI  - Experience feedback committee in emergency medicine: a tool for security
      management.
AB  - OBJECTIVE: Emergency departments are high-risk structures. The objective was to
      analyse the functioning of an experience feedback committee (EFC), a security
      management tool for the analysis of incidents in a medical department. METHODS:
      We conducted a descriptive study based on the analysis of the written documents
      produced by the EFC between November 2009 and May 2012. We performed a double
      analysis of all incident reports, meeting minutes and analysis reports. RESULTS:
      During the study period, there were 22 meetings attended by 15 professionals. 471
      reported incidents were transmitted to the EFC. Most of them (95%) had no
      consequence for the patients. Only one reported incident led to the patient's
      death. 12 incidents were analysed thoroughly and the committee decided to set up
      14 corrective actions, including eight guideline writing actions, two staff
      trainings, two resource materials provisions and two organisational changes.
      CONCLUSIONS: The staff took part actively in the EFC. Following the analysis of
      incidents, the EFC was able to set up actions at the departmental level. Thus, an
      EFC seems to be an appropriate security management tool for an emergency
      department.

PMID- 23964064
TI  - A pooled analysis of alcohol consumption and risk of multiple myeloma in the
      international multiple myeloma consortium.
AB  - BACKGROUND: Recent findings suggest that alcohol consumption may reduce risk of
      multiple myeloma. METHODS: To better understand this relationship, we conducted
      an analysis of six case-control studies participating in the International
      Multiple Myeloma Consortium (1,567 cases, 7,296 controls). Summary ORs and 95%
      confidence intervals (CI) relating different measures of alcohol consumption and
      multiple myeloma risk were computed by unconditional logistic regression with
      adjustment for age, race, and study center. RESULTS: Cases were significantly
      less likely than controls to report ever drinking alcohol (men: OR = 0.72; 95%
      CI, 0.59-0.89; women: OR = 0.81; 95% CI, 0.68-0.95). The inverse association with
      multiple myeloma was stronger when comparing current to never drinkers (men: OR =
      0.57; 95% CI, 0.45-0.72; women: OR = 0.55; 95% CI, 0.45-0.68), but null among
      former drinkers. We did not observe an exposure-response relationship with
      increasing alcohol frequency, duration, or cumulative lifetime consumption.
      Additional adjustment for body mass index, education, or smoking did not affect
      our results; and the patterns of association were similar for each type of
      alcohol beverage examined. CONCLUSIONS: Our study is, to our knowledge, the
      largest of its kind to date, and our findings suggest that alcohol consumption
      may be associated with reduced risk of multiple myeloma. IMPACT: Prospective
      studies, especially those conducted as pooled analyses with large sample sizes,
      are needed to confirm our findings and further explore whether alcohol
      consumption provides true biologic protection against this rare, highly fatal
      malignancy.

PMID- 23964065
TI  - Electrophysiological and anatomical differences of the slow pathway between the
      fast-slow form and slow-slow form of atrioventricular nodal reentrant
      tachycardia.
AB  - AIMS: This study aimed to clarify whether electrophysiological and anatomical
      properties of the slow pathway (SP) could be different between the fast-slow form
      (F/S) and the slow-slow form (S/S) atrioventricular nodal reentrant tachycardia
      (AVNRT). METHODS AND RESULTS: Nine patients with F/S and 15 patients with S/S of
      atypical AVNRT were studied. The patients with S/S were divided into two groups;
      those with the anterograde SP being eliminated (S/S aSP-E) or preserved (S/S aSP
      P) during catheter ablation. HA (CS-His) was determined as the difference of the
      shortest HA interval between the His bundle region and the coronary sinus (CS)
      region. The ratio of the amplitudes of atrial and ventricular potential (A/V
      ratio) of the successful ablation site of the SP was also evaluated. Effective
      refractory period of the retrograde SP was shorter and HA intervals during both
      tachycardia and ventricular pacing were longer in F/S than in S/S. HA (CS-His)
      did not differ between F/S and S/S (-4.3 +/- 20.2 vs.-4.4 +/- 18.4 ms, NS). The
      A/V ratio was significantly greater in the S/S aSP-P group compared with the both
      groups of F/S and S/S aSP-E (0.83 +/- 0.29 vs. 0.38 +/- 0.09 and 0.26 +/- 0.15
      ms, P < 0.01). CONCLUSION: Properties of the retrograde SP differ between F/S and
      S/S of AVNRT. Fast-slow form may utilize the same pathway for the retrograde
      conduction as the anterograde SP in S/S.

PMID- 23964066
TI  - Neurons in the basal forebrain project to the cortex in a complex topographic
      organization that reflects corticocortical connectivity patterns: an experimental
      study based on retrograde tracing and 3D reconstruction.
AB  - The most prominent feature of the Basal Forebrain (BF) is the collection of large
      cortically projecting neurons (basal nucleus of Meynert) that serve as the
      primary source of cholinergic input to the entire cortical mantle. Despite its
      broad involvement in cortical activation, attention, and memory, the functional
      details of the BF are not well understood due to the anatomical complexity of the
      region. This study tested the hypothesis that basalocortical connections reflect
      cortical connectivity patterns. Distinct retrograde tracers were deposited into
      various frontal and posterior cortical areas, and retrogradely labeled
      cholinergic and noncholinergic neurons were mapped in the BF. Concurrently, we
      mapped retrogradely labeled cells in posterior cortical areas that project to
      various frontal areas, and all cell populations were combined in the same
      coordinate system. Our studies suggest that the cholinergic and noncholinergic
      projections to the neocortex are not diffuse, but instead, are organized into
      segregated or overlapping pools of projection neurons. The extent of overlap
      between BF populations projecting to the cortex depends on the degree of
      connectivity between the cortical targets of these projection populations. We
      suggest that the organization of projections from the BF may enable parallel
      modulation of multiple groupings of interconnected yet nonadjacent cortical
      areas. 

PMID- 23964068
TI  - QRFP induces aldosterone production via PKC and T-type calcium channel-mediated
      pathways in human adrenocortical cells: evidence for a novel role of GPR103.
AB  - Hormonal regulation of adrenal function occurs primarily through activation of
      GPCRs. GPCRs are central to many of the body's endocrine and neurotransmitter
      pathways. Recently, it was shown that activation of GPR103 by its ligand QRFP
      induced feeding, locomotor activity, and metabolic rate, and QRFP is bioactive in
      adipose tissue of obese individuals. Given that the adrenal gland is a pivotal
      organ for energy balance and homeostasis, we hypothesized that GPR103 and QRFP
      are involved in steroidogenic responses. Using qRT-PCR and immunohistochemistry,
      we mapped both GPR103 and QRFP in human fetal and adult adrenal gland as well as
      rat adrenals. Both were primarily localized in the adrenal cortex but not in the
      medulla. Activation of GPR103 in human adrenocortical H295R cells led to a
      decrease in forskolin-increased cAMP and an increase of intracellular Ca(2+)
      levels. In addition, treatment of H295R cells with QRFP induced aldosterone and
      cortisol secretion as measured by ELISA. These increases were accompanied by
      increased expression and activity of StAR, CYB11B1, and CYP11B2 as assessed by
      qRT-PCR and luciferase reporter assay, respectively. Using specific inhibitors,
      we also demonstrated that aldosterone induction involves MAPK, PKC, and/or T-type
      Ca(2+) channel-dependent pathways. These novel data demonstrate that QRFP induces
      adrenal steroidogenesis in vitro by regulating key steroidogenic enzymes
      involving MAPK/PKC and Ca(2+) signaling pathways.

PMID- 23964067
TI  - Plasticity in unimodal and multimodal brain areas reflects multisensory changes
      in self-face identification.
AB  - Nothing provides as strong a sense of self as seeing one's face. Nevertheless, it
      remains unknown how the brain processes the sense of self during the multisensory
      experience of looking at one's face in a mirror. Synchronized visuo-tactile
      stimulation on one's own and another's face, an experience that is akin to
      looking in the mirror but seeing another's face, causes the illusory experience
      of ownership over the other person's face and changes in self-recognition. Here,
      we investigate the neural correlates of this enfacement illusion using fMRI. We
      examine activity in the human brain as participants experience tactile
      stimulation delivered to their face, while observing either temporally
      synchronous or asynchronous tactile stimulation delivered to another's face on
      either a specularly congruent or incongruent location. Activity in the
      multisensory right temporo-parietal junction, intraparietal sulcus, and the
      unimodal inferior occipital gyrus showed an interaction between the synchronicity
      and the congruency of the stimulation and varied with the self-reported strength
      of the illusory experience, which was recorded after each stimulation block. Our
      results highlight the important interplay between unimodal and multimodal
      information processing for self-face recognition, and elucidate the
      neurobiological basis for the plasticity required for identifying with our
      continuously changing visual appearance. 

PMID- 23964069
TI  - Higher activation of autophagy in skeletal muscle of mice during endurance
      exercise in the fasted state.
AB  - Activation of autophagy in skeletal muscle has been reported in response to
      endurance exercise and food deprivation independently. The purpose of this study
      was to evaluate whether autophagy was more activated when both stimuli were
      combined, namely when endurance exercise was performed in a fasted rather than a
      fed state. Mice performed a low-intensity running exercise (10 m/min for 90min)
      in both dietary states after which the gastrocnemius muscles were removed. LC3b
      II, a marker of autophagosome presence, increased in both conditions, but the
      increase was higher in the fasted state. Other protein markers of autophagy, like
      Gabarapl1-II and Atg12 conjugated form as well as mRNA of Lc3b, Gabarapl1, and
      p62/Sqstm1 were increased only when exercise was performed in a fasted state. The
      larger activation of autophagy by exercise in a fasted state was associated with
      a larger decrease in plasma insulin and phosphorylation of Akt(Ser473),
      Akt(Thr308), FoxO3a(Thr32), and ULK1(Ser757). AMPKalpha(Thr172), ULK1(Ser317),
      and ULK1(Ser555) remained unchanged in both conditions, whereas
      p38(Thr180/Tyr182) increased during exercise to a similar extent in the fasted
      and fed conditions. The marker of mitochondrial fission DRP1(Ser616) was
      increased by exercise independently of the nutritional status. Changes in
      mitophagy markers BNIP3 and Parkin suggest that mitophagy was increased during
      exercise in the fasted state. In conclusion, our results highlight a major
      implication of the insulin-Akt-mTOR pathway and its downstream targets FoxO3a and
      ULK1 in the larger activation of autophagy observed when exercise is performed in
      a fasted state compared with a fed state. 

PMID- 23964070
TI  - Metformin prevents liver tumorigenesis induced by high-fat diet in C57Bl/6 mice.
AB  - The prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic
      steatohepatitis (NASH) is increasing with the growing epidemics of obesity and
      diabetes. NAFLD encompasses a clinicopathologic spectrum of disease ranging from
      isolated hepatic steatosis to NASH, which is a more aggressive form of fatty
      liver disease, to cirrhosis and, finally, hepatocellular carcinoma (HCC). The
      exact mechanism behind the development of HCC in NASH remains unclear; however,
      it has been established that hepatic steatosis is the important risk factor in
      the development of HCC. Metformin has recently drawn attention because of its
      potential antitumor effect. Here, we investigated the effects of metformin on
      high-fat diet (HFD)-induced liver tumorigenesis, using a mouse model of NASH and
      liver tumor. Metformin prevented long-term HFD-induced liver tumorigenesis in
      C57Bl/6 mice. Of note, metformin failed to protect against liver tumorigenesis in
      mice that had already begun to develop NAFLD. Metformin improved short-term HFD
      induced fat accumulation in the liver, associated with the suppression of adipose
      tissue inflammation. Collectively, these results suggest that metformin may
      prevent liver tumorigenesis via suppression of liver fat accumulation in the
      early stage, before the onset of NAFLD, which seems to be associated with a delay
      in the development of inflammation of the adipose tissue. 

PMID- 23964071
TI  - Direct calorimetry identifies deficiencies in respirometry for the determination
      of resting metabolic rate in C57Bl/6 and FVB mice.
AB  - Substantial research efforts have been aimed at identifying novel targets to
      increase resting metabolic rate (RMR) as an adjunct approach to the treatment of
      obesity. Respirometry (one form of "indirect calorimetry") is unquestionably the
      dominant technique used in the obesity research field to assess RMR in vivo,
      although this method relies upon a lengthy list of assumptions that are likely to
      be violated in pharmacologically or genetically manipulated animals. A "total"
      calorimeter, including a gradient layer direct calorimeter coupled to a
      conventional respirometer, was used to test the accuracy of respirometric-based
      estimations of RMR in laboratory mice (Mus musculus Linnaeus) of the C57Bl/6 and
      FVB background strains. Using this combined calorimeter, we determined that
      respirometry underestimates RMR of untreated 9- to 12-wk-old male mice by ~10
      12%. Quantitative and qualitative differences resulted between methods for
      untreated C57Bl/6 and FVB mice, C57Bl/6 mice treated with ketamine-xylazine
      anesthesia, and FVB mice with genetic deletion of the angiotensin II type 2
      receptor. We conclude that respirometric methods underestimate RMR in mice in a
      magnitude that is similar to or greater than the desired RMR effects of novel
      therapeutics. Sole reliance upon respirometry to assess RMR in mice may lead to
      false quantitative and qualitative conclusions regarding the effects of novel
      interventions. Increased use of direct calorimetry for the assessment of RMR and
      confirmation of respirometry results and the reexamination of previously
      discarded potential obesity therapeutics are warranted.

PMID- 23964072
TI  - Leveraging the national cyberinfrastructure for biomedical research.
AB  - In the USA, the national cyberinfrastructure refers to a system of research
      supercomputer and other IT facilities and the high speed networks that connect
      them. These resources have been heavily leveraged by scientists in disciplines
      such as high energy physics, astronomy, and climatology, but until recently they
      have been little used by biomedical researchers. We suggest that many of the 'Big
      Data' challenges facing the medical informatics community can be efficiently
      handled using national-scale cyberinfrastructure. Resources such as the Extreme
      Science and Discovery Environment, the Open Science Grid, and Internet2 provide
      economical and proven infrastructures for Big Data challenges, but these
      resources can be difficult to approach. Specialized web portals, support centers,
      and virtual organizations can be constructed on these resources to meet defined
      computational challenges, specifically for genomics. We provide examples of how
      this has been done in basic biology as an illustration for the biomedical
      informatics community. 

PMID- 23964073
TI  - Do reduction and healing of the bony fragment really matter in arthroscopic bony
      Bankart reconstruction?: a prospective study with clinical and computed
      tomography evaluations.
AB  - BACKGROUND: Bony Bankart lesions can be treated with arthroscopic repair.
      However, few studies have evaluated the importance of bony fragment reduction and
      healing to stability of the glenohumeral joint after arthroscopic bony Bankart
      repair. PURPOSE: To evaluate functional results after surgery and determine the
      correlation between reduction and healing of the fracture and postoperative
      stability of the glenohumeral joint. STUDY DESIGN: Case series; Level of
      evidence, 4. METHODS: A total of 50 patients (47 men, 3 women; average age, 27.6
      years; range, 16.5-50.1 years) with bony Bankart lesions and recurrent anterior
      shoulder dislocations were treated with arthroscopic reduction and internal
      fixation with suture anchors. The average follow-up period was 32.5 months
      (range, 24.3-61.2 months). Preoperative and postoperative range of motion and
      American Shoulder and Elbow Surgeons (ASES), Constant-Murley, and Rowe scores
      were compared to evaluate the results of the surgeries. Sequential 3-dimensional
      computed tomography (CT) scans were available for 37 patients and were analyzed
      to investigate the effect of the bony defect of the glenoid and the correlation
      between the success of the surgery and reduction and healing of the bony
      fragment. RESULTS: After surgery, active forward elevation was significantly
      improved (P < .05). No significant differences were found regarding external and
      internal rotations after surgery. The ASES, Constant-Murley, and Rowe scores
      improved significantly after surgery. Redislocations occurred in 3 patients, and
      a positive anterior apprehension sign was detected in 1 patient during follow-up.
      The overall failure rate was 8.0% (4/50). The CT scans during the follow-up
      period showed a nonunion of the bony fragment in 13.5% of cases (5/37). The
      reconstructed size of the glenoid was <80% in 3 of the 4 failure cases but >80%
      in all of the successful cases. CONCLUSION: Arthroscopic reduction and fixation
      of a bony Bankart lesion can achieve good results in selected cases. The size of
      the reconstructed glenoid is crucial to the success of the surgery.

PMID- 23964075
TI  - Auto ADP-ribosylation of NarE, a Neisseria meningitidis ADP-ribosyltransferase,
      regulates its catalytic activities.
AB  - NarE is an arginine-specific mono-ADP-ribosyltransferase identified in Neisseria
      meningitidis that requires the presence of iron in a structured cluster for its
      enzymatic activities. In this study, we show that NarE can perform auto-ADP
      ribosylation. This automodification occurred in a time- and NAD-concentration
      dependent manner; was inhibited by novobiocin, an ADP-ribosyltransferase
      inhibitor; and did not occur when NarE was heat inactivated. No reduction in
      incorporation was evidenced in the presence of high concentrations of ATP, GTP,
      ADP-ribose, or nicotinamide, which inhibits NAD-glycohydrolase, impeding the
      formation of free ADP-ribose. Based on the electrophoretic profile of NarE on
      auto-ADP-ribosylation and on the results of mutagenesis and mass spectrometry
      analysis, the auto-ADP-ribosylation appeared to be restricted to the addition of
      a single ADP-ribose. Chemical stability experiments showed that the ADP-ribosyl
      linkage was sensitive to hydroxylamine, which breaks ADP-ribose-arginine bonds.
      Site-directed mutagenesis suggested that the auto-ADP-ribosylation site occurred
      preferentially on the R(7) residue, which is located in the region I of the ADP
      ribosyltransferase family. After auto-ADP-ribosylation, NarE showed a reduction
      in ADP-ribosyltransferase activity, while NAD-glycohydrolase activity was
      increased. Overall, our findings provide evidence for a novel intramolecular
      mechanism used by NarE to regulate its enzymatic activities.

PMID- 23964074
TI  - Lysosomal alkalinization, lipid oxidation, and reduced phagosome clearance
      triggered by activation of the P2X7 receptor.
AB  - Lysosomal enzymes function optimally at low pH; as accumulation of waste material
      contributes to cell aging and disease, dysregulation of lysosomal pH may
      represent an early step in several pathologies. Here, we demonstrate that
      stimulation of the P2X7 receptor (P2X7R) for ATP alkalinizes lysosomes in
      cultured human retinal pigmented epithelial (RPE) cells and impairs lysosomal
      function. P2X7R stimulation did not kill RPE cells but alkalinized lysosomes by
      0.3 U. Receptor stimulation also elevated cytoplasmic Ca(2+); Ca(2+) influx was
      necessary but not sufficient for lysosomal alkalinization. P2X7R stimulation
      decreased access to the active site of cathepsin D. Interestingly, lysosomal
      alkalinization was accompanied by a rise in lipid oxidation that was prevented by
      P2X7R antagonism. Likewise, the autofluorescence of phagocytosed photoreceptor
      outer segments increased by lysosomal alkalinization was restored 73% by a P2X7R
      antagonist. Together, this suggests that endogenous autostimulation of the P2X7R
      may oxidize lipids and impede clearance. The P2X7R was expressed on apical and
      basolateral membranes of mouse RPE; mRNA expression of P2X7R and extracellular
      ATP marker NTPDase1 was raised in RPE tissue from the ABCA4(-/-) mouse model of
      Stargardt's retinal degeneration. In summary, P2X7R stimulation raises lysosomal
      pH and impedes lysosomal function, suggesting a possible role for overstimulation
      in diseases of accumulation.

PMID- 23964076
TI  - De novo Ixodes ricinus salivary gland transcriptome analysis using two next
      generation sequencing methodologies.
AB  - Tick salivary gland (SG) proteins possess powerful pharmacologic properties that
      facilitate tick feeding and pathogen transmission. For the first time, SG
      transcriptomes of Ixodes ricinus, an important disease vector for humans and
      animals, were analyzed using next-generation sequencing. SGs were collected from
      different tick life stages fed on various animal species, including cofeeding of
      nymphs and adults on the same host. Four cDNA samples were sequenced,
      discriminating tick SG transcriptomes of early- and late-feeding nymphs or
      adults. In total, 441,381,454 pyrosequencing reads and 67,703,183 Illumina reads
      were assembled into 272,220 contigs, of which 34,560 extensively annotated coding
      sequences are disclosed; 8686 coding sequences were submitted to GenBank.
      Overall, 13% of contigs were classified as secreted proteins that showed
      significant differences in the transcript representation among the 4 SG samples,
      including high numbers of sample-specific transcripts. Detailed phylogenetic
      reconstructions of two relatively abundant SG-secreted protein families
      demonstrated how this study improves our understanding of the molecular evolution
      of hematophagy in arthropods. Our data significantly increase the available
      genomic information for I. ricinus and form a solid basis for future tick
      genome/transcriptome assemblies and the functional analysis of effectors that
      mediate the feeding physiology and parasite-vector interaction of I. ricinus.

PMID- 23964077
TI  - Administration of granulocyte colony-stimulating factor induces immunomodulation,
      recruitment of T regulatory cells, reduction of myocarditis and decrease of
      parasite load in a mouse model of chronic Chagas disease cardiomyopathy.
AB  - Chagas disease, caused by Trypanosoma cruzi infection, is a leading cause of
      heart failure in Latin American countries. In a previous study, we showed
      beneficial effects of granulocyte colony-stimulating factor (G-CSF)
      administration in the heart function of mice with chronic T. cruzi infection.
      Presently, we investigated the mechanisms by which this cytokine exerts its
      beneficial effects. Mice chronically infected with T. cruzi were treated with
      human recombinant G-CSF (3 courses of 200 MUg/kg/d for 5 d). Inflammation and
      fibrosis were reduced in the hearts of G-CSF-treated mice, compared with the
      hearts of vehicle-treated mice, which correlated with decreased syndecan-4,
      intercellular adhesion molecule-1, and galectin-3 expressions. Marked reductions
      in interferon-gamma and tumor necrosis factor-alpha and increased interleukin-10
      and transforming growth factor-beta were found after G-CSF administration.
      Because the therapy did not induce a Th1 to Th2 immune response deviation, we
      investigated the role of regulatory T (Treg) cells. A significant increase in
      CD3(+)Foxp3(+) cells was observed in the hearts of G-CSF-treated mice. In
      addition, a reduction of parasitism was observed after G-CSF treatment. Our
      results indicate a role of Treg cells in the immunosuppression induced by G-CSF
      treatment and reinforces its potential therapeutic use for patients with Chagas
      disease.

PMID- 23964078
TI  - Fluid shear stress-induced osteoarthritis: roles of cyclooxygenase-2 and its
      metabolic products in inducing the expression of proinflammatory cytokines and
      matrix metalloproteinases.
AB  - The mechanical overloading of cartilage is involved in the pathophysiology of
      osteoarthritis (OA) by both biochemical and mechanical pathways. The application
      of fluid shear stress to chondrocytes recapitulates the earmarks of OA, as
      evidenced by the release of proinflammatory cytokines (PICs), matrix
      metalloproteinases (MMPs), and apoptotic factors. Dysregulations or mutations in
      these genes might directly cause OA in addition to determining the stage at which
      OA becomes apparent, the joint sites involved, and the severity of the disease
      and how rapidly it progresses. However, the underlying mechanisms remain unknown.
      In this review, we propose that the dysregulation of cyclooxygenase-2 (COX-2) is
      associated with fluid shear stress-induced OA via its metabolic products at
      different stages of the disease. Indeed, high fluid shear stress rapidly induces
      the production of PICs and MMPs via COX-2-derived prostaglandin (PG)E2 at the
      early stage of OA. In contrast, prolonged shear exposure (>12 h) aggravates the
      condition by concurrently up-regulating the expression of proapoptotic genes and
      down-regulating the expression of antiapoptotic genes in a 15-deoxy-Delta (12,14)
      prostaglandin J2 (15d-PGJ2)-dependent manner at the late stage of disease. These
      observations may help to resolve long-standing questions in OA progression and
      provide insight for development of strategies to treat and combat OA.

PMID- 23964079
TI  - The novel complement inhibitor human CUB and Sushi multiple domains 1 (CSMD1)
      protein promotes factor I-mediated degradation of C4b and C3b and inhibits the
      membrane attack complex assembly.
AB  - CUB and Sushi multiple domains 1 (CSMD1) is a transmembrane protein containing 15
      consecutive complement control protein (CCP) domains, which are characteristic
      for complement inhibitors. We expressed a membrane-bound fragment of human CSMD1
      composed of the 15 C-terminal CCP domains and demonstrated that it inhibits
      deposition of C3b by the classical pathway on the surface of Chinese hamster
      ovary cells by 70% at 6% serum and of C9 (component of membrane attack complex)
      by 90% at 1.25% serum. Furthermore, this fragment of CSMD1 served as a cofactor
      to factor I-mediated degradation of C3b. In all functional assays performed, well
      characterized complement inhibitors were used as positive controls, whereas
      Coxsackie adenovirus receptor, a protein with no effect on complement, was a
      negative control. Moreover, attenuation of expression in human T47 breast cancer
      cells that express endogenous CSMD1 significantly increased C3b deposition on
      these cells by 45% at 8% serum compared with that for the controls. Furthermore,
      by expressing a soluble 17-21 CCP fragment of CSMD1, we found that CSMD1 inhibits
      complement by promoting factor I-mediated C4b/C3b degradation and inhibition of
      MAC assembly at the level of C7. Our results revealed a novel complement
      inhibitor for the classical and lectin pathways.

PMID- 23964080
TI  - VBP1 facilitates proteasome and autophagy-mediated degradation of MutS homologue
      hMSH4.
AB  - Ubiquitination is an important mechanism for the regulation of diverse cellular
      functions, including proteolysis and DNA repair. The human MutS family protein
      hMSH4 functions in meiotic recombinational DNA double-strand break (DSB) repair.
      It was previously observed that hMSH4 interacts with the von Hippel-Lindau
      binding protein 1 (VBP1), a partner of the VHL ubiquitin E3 ligase as well as a
      subunit of the prefoldin complex. In this study we address how ubiquitination
      regulates the homeostasis of hMSH4 in the human embryonic kidney cell line
      HEK293T. We demonstrate that VBP1 targets hMSH4 for degradation and identify a
      new VBP1 binding partner, p97, an AAA(+) ATPase involved in protein degradation
      and DNA damage response. VBP1, VHL, and p97 coexist in the hMSH4 immunocomplex
      and regulate the polyubiquitination of hMSH4. Furthermore, the results of this
      study demonstrate that VBP1 acts together with p97 to regulate hMSH4 degradation.
      Overall, this study has revealed a molecular mechanism by which VBP1 controls the
      levels of hMSH4 by ubiquitination in mitotic cells. Such a mechanism may be
      important for controlling the role of hMSH4 in regulating homologous
      recombination and nonhomologous DNA end joining-mediated DSB repair in human
      cells.

PMID- 23964081
TI  - Diet-induced obesity, adipose inflammation, and metabolic dysfunction correlating
      with PAR2 expression are attenuated by PAR2 antagonism.
AB  - Excessive uptake of fatty acids and glucose by adipose tissue triggers adipocyte
      dysfunction and infiltration of immune cells. Altered metabolic homeostasis in
      adipose tissue promotes insulin resistance, type 2 diabetes, hypertension, and
      cardiovascular disease. Inflammatory and metabolic processes are mediated by
      certain proteolytic enzymes that share a common cellular target, protease
      activated receptor 2 (PAR2). This study showed that human and rat obesity
      correlated in vivo with increased expression of PAR2 in adipose tissue, primarily
      in stromal vascular cells (SVCs) including macrophages. PAR2 was expressed more
      than other PARs on human macrophages and was increased by dietary fatty acids
      (palmitic, stearic, and myristic). A novel PAR2 antagonist, GB88 (5-isoxazoyl-Cha
      Ile-spiroindene-1,4-piperidine), given orally at 10 mg/kg/d (wk 8-16) reduced
      body weight by ~10% in obese rats fed a high-carbohydrate high-fat (HCHF) diet
      for 16 wk, and strongly attenuated adiposity, adipose tissue inflammation,
      infiltrated macrophages and mast cells, insulin resistance, and cardiac fibrosis
      and remodeling; while reversing liver and pancreatic dysfunction and normalizing
      secretion of PAR2-directed glucose-stimulated insulin secretion in MIN6 beta
      cells. In summary, PAR2 is a new biomarker for obesity, and its expression is
      stimulated by dietary fatty acids; PAR2 is a substantial contributor to
      inflammatory and metabolic dysfunction; and a PAR2 antagonist inhibits diet
      induced obesity and inflammatory, metabolic, and cardiovascular dysfunction.

PMID- 23964086
TI  - Long-term developmental outcome of children with a fetal diagnosis of isolated
      inferior vermian hypoplasia.
AB  - OBJECTIVES: Isolated inferior vermian hypoplasia (iiVH) is one of the most common
      fetal cerebellar anomalies presenting for fetal neurological counselling with
      controversial postnatal neurodevelopmental outcome. In the present study, we
      characterised the long-term neurodevelopmental outcome of prenatally diagnosed
      iiVH at school age. DESIGN AND PATIENTS: We prospectively followed 20 children
      with fetal MRI diagnosis of iiVH including their postnatal MRI result and
      developmental outcome at school age (mean 6.1 years+/-1.9 years SD) using a
      comprehensive age-appropriate developmental testing battery, which encompassed
      cognitive, language, social and behavioural domains. Parental stress level and
      socioeconomic status were also evaluated. RESULTS: All children with postnatally
      confirmed iiVH had a normal neurodevelopmental outcome. A subgroup of children
      (2/20) who demonstrated cognitive delays and behavioural impairments had more
      extensive cerebellar malformation. Despite a normal developmental outcome, the
      parents of children with postnatally confirmed iiVH had higher parental stress
      compared with those parents whose children had normal postnatal MRI. CONCLUSIONS:
      Children with postnatally confirmed iiVH show age appropriate functioning at
      school age. Postnatal MRI is important to confirm the diagnosis of iiVH and to
      exclude associated anomalies that impact neurodevelopmental outcome. A diagnosis
      of iiVH is associated with persistent elevated parental stress despite normal
      developmental outcomes in these children suggesting the need for ongoing parental
      support.

PMID- 23964087
TI  - Editorial commentary: intussusception and rotavirus vaccination--balancing risk
      against benefit.

PMID- 23964089
TI  - Do penicillins really increase the frequency of a rash when given during Epstein
      Barr Virus primary infection?

PMID- 23964088
TI  - Invasive methicillin-resistant Staphylococcus aureus infections among patients on
      chronic dialysis in the United States, 2005-2011.
AB  - BACKGROUND: Approximately 15 700 invasive methicillin-resistant Staphylococcus
      aureus (MRSA) infections occurred in US dialysis patients in 2010. Frequent
      hospital visits and prolonged bloodstream access, especially via central venous
      catheters (CVCs), are risk factors among hemodialysis patients. We describe the
      epidemiology of and recent trends in invasive MRSA infections among dialysis
      patients. METHODS: We analyzed population-based data from 9 US metropolitan areas
      from 2005 to 2011. Cases were defined as MRSA isolated from a normally sterile
      body site in a surveillance area resident who received dialysis, and were
      classified as hospital-onset (HO; culture collected >3 days after hospital
      admission) or healthcare-associated community-onset (HACO; all others). Incidence
      was calculated using denominators from the US Renal Data System. Temporal trends
      in incidence and national estimates were calculated controlling for age, sex, and
      race. RESULTS: From 2005 to 2011, 7489 cases were identified; 85.7% were HACO
      infections, and 93.2% were bloodstream infections. Incidence of invasive MRSA
      infections decreased from 6.5 to 4.2 per 100 dialysis patients (annual decrease,
      7.3%) with annual decreases of 6.7% for HACO and 10.5% for HO cases. Among cases
      identified during 2009-2011, 70% of patients were hospitalized in the year prior
      to infection. Among hemodialysis cases, 60.4% of patients were dialyzed through a
      CVC. The 2011 national estimated number of MRSA infections was 15 169.
      CONCLUSIONS: There has been a substantial decrease in invasive MRSA infection
      incidence among dialysis patients. Most cases had previous hospitalizations,
      suggesting that efforts to control MRSA in hospitals might have contributed to
      the declines. Infection prevention measures should include improved vascular
      access and CVC care.

PMID- 23964090
TI  - Intussusception risk and disease prevention associated with rotavirus vaccines in
      Australia's National Immunization Program.
AB  - BACKGROUND: Estimates of the risk of intussusception (IS) associated with
      currently licensed rotavirus vaccines (RV1 [Rotarix; GSK] and RV5 [RotaTeq;
      Merck]) diverge. Contemporaneous introduction of both vaccines in Australia
      enabled a population-based assessment of risk. METHODS: Confirmed cases of IS in
      infants aged 1 to <12 months were identified from national hospitalization
      databases, supplemented by active hospital-based surveillance, from July 2007
      through June 2010. Vaccination histories were verified by the Australian
      Childhood Immunisation Register, which was also used to identify age-matched
      controls. Self-controlled case series and case-control methods were used to
      assess the risk of IS associated with both vaccines in prespecified periods after
      vaccination. The estimated burden of vaccine-attributable IS was compared with
      estimated reductions in gastroenteritis hospitalizations. RESULTS: Based on 306
      confirmed cases of IS, the relative incidence of IS in the 1-7-day period after
      the first vaccine dose, was 6.8 (95% confidence interval, 2.4-19.0; P < .001) for
      RV1, and 9.9 (95% confidence interval, 3.7-26.4; P < .001) for RV5. There was a
      smaller increased risk 1-7 days after the second dose of each vaccine. The case
      control analysis gave similar results. We estimate an excess of 14 IS cases and
      >6500 fewer gastroenteritis hospitalizations in young children annually in
      Australia after vaccine introduction. CONCLUSIONS: We found a similarly increased
      risk of IS after both vaccines, but the balance of benefits and risks at
      population level was highly favorable, a finding likely to extend to other
      settings despite varying incidence of IS and potentially higher morbidity and
      mortality from both gastroenteritis and IS.

PMID- 23964091
TI  - Chromatin targeting drugs in cancer and immunity.
AB  - Recent advances in the enzymology of transcription and chromatin regulation have
      led to the discovery of proteins that play a prominent role in cell
      differentiation and the maintenance of specialized cell functions. Knowledge
      about post-synthetic DNA and histone modifications as well as information about
      the rules that guide the formation of multimolecular chromatin-bound complexes
      have helped to delineate gene-regulating pathways and describe how these pathways
      are altered in various pathological conditions. The present review focuses on the
      emerging area of therapeutic interference with chromatin function for the purpose
      of cancer treatment and immunomodulation. 

PMID- 23964092
TI  - The FHA and BRCT domains recognize ADP-ribosylation during DNA damage response.
AB  - Poly-ADP-ribosylation is a unique post-translational modification participating
      in many biological processes, such as DNA damage response. Here, we demonstrate
      that a set of Forkhead-associated (FHA) and BRCA1 C-terminal (BRCT) domains
      recognizes poly(ADP-ribose) (PAR) both in vitro and in vivo. Among these FHA and
      BRCT domains, the FHA domains of APTX and PNKP interact with iso-ADP-ribose, the
      linkage of PAR, whereas the BRCT domains of Ligase4, XRCC1, and NBS1 recognize
      ADP-ribose, the basic unit of PAR. The interactions between PAR and the FHA or
      BRCT domains mediate the relocation of these domain-containing proteins to DNA
      damage sites and facilitate the DNA damage response. Moreover, the interaction
      between PAR and the NBS1 BRCT domain is important for the early activation of ATM
      during DNA damage response and ATM-dependent cell cycle checkpoint activation.
      Taken together, our results demonstrate two novel PAR-binding modules that play
      important roles in DNA damage response. 

PMID- 23964093
TI  - Epigenomic enhancer annotation reveals a key role for NFIX in neural stem cell
      quiescence.
AB  - The majority of neural stem cells (NSCs) in the adult brain are quiescent, and
      this fraction increases with aging. Although signaling pathways that promote NSC
      quiescence have been identified, the transcriptional mechanisms involved are
      mostly unknown, largely due to lack of a cell culture model. In this study, we
      first demonstrate that NSC cultures (NS cells) exposed to BMP4 acquire cellular
      and transcriptional characteristics of quiescent cells. We then use epigenomic
      profiling to identify enhancers associated with the quiescent NS cell state.
      Motif enrichment analysis of these enhancers predicts a major role for the
      nuclear factor one (NFI) family in the gene regulatory network controlling NS
      cell quiescence. Interestingly, we found that the family member NFIX is robustly
      induced when NS cells enter quiescence. Using genome-wide location analysis and
      overexpression and silencing experiments, we demonstrate that NFIX has a major
      role in the induction of quiescence in cultured NSCs. Transcript profiling of NS
      cells overexpressing or silenced for Nfix and the phenotypic analysis of the
      hippocampus of Nfix mutant mice suggest that NFIX controls the quiescent state by
      regulating the interactions of NSCs with their microenvironment. 

PMID- 23964094
TI  - Redistribution of the Lamin B1 genomic binding profile affects rearrangement of
      heterochromatic domains and SAHF formation during senescence.
AB  - Senescence is a stress-responsive form of stable cell cycle exit. Senescent cells
      have a distinct gene expression profile, which is often accompanied by the
      spatial redistribution of heterochromatin into senescence-associated
      heterochromatic foci (SAHFs). Studying a key component of the nuclear lamina
      lamin B1 (LMNB1), we report dynamic alterations in its genomic profile and their
      implications for SAHF formation and gene regulation during senescence. Genome
      wide mapping reveals that LMNB1 is depleted during senescence, preferentially
      from the central regions of lamina-associated domains (LADs), which are enriched
      for Lys9 trimethylation on histone H3 (H3K9me3). LMNB1 knockdown facilitates the
      spatial relocalization of perinuclear H3K9me3-positive heterochromatin, thus
      promoting SAHF formation, which could be inhibited by ectopic LMNB1 expression.
      Furthermore, despite the global reduction in LMNB1 protein levels, LMNB1 binding
      increases during senescence in a small subset of gene-rich regions where H3K27me3
      also increases and gene expression becomes repressed. These results suggest that
      LMNB1 may contribute to senescence in at least two ways due to its uneven genome
      wide redistribution: first, through the spatial reorganization of chromatin and,
      second, through gene repression. 

PMID- 23964095
TI  - A new role for the cellular PABP repressor Paip2 as an innate restriction factor
      capable of limiting productive cytomegalovirus replication.
AB  - The capacity of polyadenylate-binding protein PABPC1 (PABP1) to stimulate
      translation is regulated by its repressor, Paip2. Paradoxically, while PABP
      accumulation promotes human cytomegalovirus (HCMV) protein synthesis, we show
      that this is accompanied by an analogous increase in the abundance of Paip2 and
      EDD1, an E3 ubiquitin ligase that destabilizes Paip2. Coordinate control of
      PABP1, Paip2, and EDD1 required the virus-encoded UL38 mTORC1 activator and
      resulted in augmented Paip2 synthesis, stability, and association with PABP1.
      Paip2 synthesis also increased following serum stimulation of uninfected normal
      fibroblasts, suggesting that this coregulation may play a role in how uninfected
      cells respond to stress. Significantly, Paip2 accumulation was dependent on PABP
      accrual, as preventing PABP1 accumulation suppressed viral replication and
      inhibited the corresponding Paip2 increase. Furthermore, depleting Paip2 restored
      the ability of infected cells to assemble the translation initiation factor
      eIF4F, promoting viral protein synthesis and replication without increasing
      PABP1. This establishes a new role for the cellular PABP1 inhibitor Paip2 as an
      innate defense that restricts viral protein synthesis and replication. Moreover,
      it illustrates how a stress-induced rise in PABP1 triggered by virus infection
      can counter and surpass a corresponding increase in Paip2 abundance and
      stability. 

PMID- 23964096
TI  - E3-ubiquitin ligase Nedd4 determines the fate of AID-associated RNA polymerase II
      in B cells.
AB  - Programmed mutagenesis of the immunoglobulin locus of B lymphocytes during class
      switch recombination (CSR) and somatic hypermutation requires RNA polymerase II
      (polII) transcription complex-dependent targeting of the DNA mutator activation
      induced cytidine deaminase (AID). AID deaminates cytidine residues on substrate
      sequences in the immunoglobulin (Ig) locus via a transcription-dependent
      mechanism, and this activity is stimulated by the RNA polII stalling cofactor
      Spt5 and the 11-subunit cellular noncoding RNA 3'-5' exonucleolytic processing
      complex RNA exosome. The mechanism by which the RNA exosome recognizes
      immunoglobulin locus RNA substrates to stimulate AID DNA deamination activity on
      its in vivo substrate sequences is an important question. Here we report that E3
      ubiquitin ligase Nedd4 destabilizes AID-associated RNA polII by a ubiquitination
      event, leading to generation of 3' end free RNA exosome RNA substrates at the Ig
      locus and other AID target sequences genome-wide. We found that lack of Nedd4
      activity in B cells leads to accumulation of RNA exosome substrates at AID target
      genes and defective CSR. Taken together, our study links noncoding RNA processing
      following RNA polII pausing with regulation of the mutator AID protein. Our study
      also identifies Nedd4 as a regulator of noncoding RNAs that are generated by
      stalled RNA polII genome-wide. 

PMID- 23964097
TI  - Molecular mass dependence of hyaluronan detection by sandwich ELISA-like assay
      and membrane blotting using biotinylated hyaluronan binding protein.
AB  - Hyaluronan (HA) is widely detected in biological samples and its concentration is
      most commonly determined by the use of a labeled specific HA binding protein
      (aggrecan G1-IGD-G2, HABP), employing membrane blotting and sandwich enzyme
      linked immunosorbent assay (ELISA)-like methods. However, the detected signal
      intensity or the quantified value obtained by using these surface-based methods
      is related to the molecular mass (M) of HA, especially for HA in the low M range
      below ~150 kDa. At the same mass or mass concentration, higher M HA gives a
      higher signal than lower M HA. We have experimentally determined the quantitative
      relationship between the M of HA (in the range 20-150 kDa) and the relative
      signal intensity in comparison with a standard HA, in a sandwich ELISA-like
      assay. An M-dependent signal correction factor (SCF) was calculated and used to
      correct the signal intensity, so that the corrected concentration value would
      more accurately reflect the true HA concentration in solution. The SCF for
      polydisperse low M HA was also calculated and compared with experimental results.
      When the molecular mass distribution of an HA sample is determined by a method
      such as gel electrophoresis, then its appropriately averaged SCF can be
      calculated and used to correct the signal in sandwich ELISA to obtain a more
      accurate concentration estimation. The correction method works for HA with M
      between ~150 and 20 kDa, but lower M HA is too poorly detected for useful
      analysis. The physical basis of the M-dependent detection is proposed to be the
      increase in detector-accessible fraction of each surface-bound molecule as M
      increases.

PMID- 23964098
TI  - Combining risk factors with faecal immunochemical test outcome for selecting CRC
      screenees for colonoscopy.
AB  - OBJECTIVE: Faecal immunochemical testing (FIT) is increasingly used in colorectal
      cancer (CRC) screening but has a less than perfect sensitivity. Combining risk
      stratification, based on established risk factors for advanced neoplasia, with
      the FIT result for allocating screenees to colonoscopy could increase the
      sensitivity and diagnostic yield of FIT-based screening. We explored the use of a
      risk prediction model in CRC screening. DESIGN: We collected data in the
      colonoscopy arm of the Colonoscopy or Colonography for Screening study, a
      multicentre screening trial. For this study 6600 randomly selected, asymptomatic
      men and women between 50 years and 75 years of age were invited to undergo
      colonoscopy. Screening participants were asked for one sample FIT (OC-sensor) and
      to complete a risk questionnaire prior to colonoscopy. Based on the questionnaire
      data and the FIT results, we developed a multivariable risk model with the
      following factors: total calcium intake, family history, age and FIT result. We
      evaluated goodness-of-fit, calibration and discrimination, and compared it with a
      model based on primary screening with FIT only. RESULTS: Of the 1426 screening
      participants, 1112 (78%) completed the questionnaire and FIT. Of these, 101
      (9.1%) had advanced neoplasia. The risk based model significantly increased the
      goodness-of-fit compared with a model based on FIT only (p<0.001). Discrimination
      improved significantly with the risk-based model (area under the receiver
      operating characteristic (ROC) curve: from 0.69 to 0.76, (p=0.02)). Calibration
      was good (Hosmer-Lemeshow test; p=0.94). By offering colonoscopy to the 102
      patients at highest risk, rather than to the 102 cases with a FIT result >50
      ng/mL, 5 more cases of advanced neoplasia would be detected (net reclassification
      improvement 0.054, p=0.073). CONCLUSIONS: Adding risk based stratification
      increases the accuracy FIT-based CRC screening and could be used in preselection
      for colonoscopy in CRC screening programmes.

PMID- 23964099
TI  - Genomic ATG16L1 risk allele-restricted Paneth cell ER stress in quiescent Crohn's
      disease.
AB  - OBJECTIVE: Although genome wide association studies have partly uncovered the
      genetic basis of Crohn's disease (CD), it remains a challenge to link genetic
      polymorphisms to functional intestinal phenotypes. Paneth cells are specialised
      antimicrobial epithelial cells localised to the small-intestinal crypt-base.
      Here, we investigate whether genomic variations in ATG16L1 affect Paneth cell
      function. DESIGN: Genomic variation of ATG16L1 (T300A, rs2241880) was determined
      in DNA from 78 patients with CD and 12 healthy controls. Paraffin-embedded ileal
      biopsies from patients with genotype AA (n=17), GA (n=38) and patients with the
      GG allele (n=23) were stained for GRP78, phospho-EIF2alpha, lysozyme, cleaved
      caspase 3, phosphohistone H3, phospho-IkappaB, p65, phospho-p38MAPK and PHLDA1.
      Microbial composition of biopsies was assessed by PCR. Disease phenotype was
      scored. RESULTS: In patients with quiescent disease but with an ATG16L1 risk
      allele, the endoplasmic reticulum (ER) stress markers GRP78 and pEIF2alpha were
      highly expressed in Paneth cells. Other CD risk gene variations did not correlate
      with Paneth cell ER stress. Functionally, patients with ER-stressed Paneth cells
      showed no changes in intestinal epithelial cells proliferation or apoptosis,
      Paneth cell or stem cell numbers, p65, phospho-IkappaB and phospho-p38 staining.
      However, a significantly increased presence of adherent-invasive Escherichia coli
      was observed in biopsies from patients with ER-stressed Paneth cells.
      Phenotypically, patients with GRP78 positive Paneth cells have relatively less
      colonic disease over ileal disease (-21%, p=0.04), more fistulas (+21%, p=0.05)
      and an increased need for intestinal surgery (+38%, p=0.002). CONCLUSIONS: The
      ATG16L1 T300A polymorphism defines a specific subtype of patients with CD,
      characterised by Paneth cell ER stress even during quiescent disease. Paneth cell
      ER stress correlates with bacterial persistence, and is thus likely to modulate
      antimicrobial functionality of this cell type in patients with CD.

PMID- 23964101
TI  - The carrier effect and T cell/B cell cooperation in the antibody response.

PMID- 23964100
TI  - Obese patients after gastric bypass surgery have lower brain-hedonic responses to
      food than after gastric banding.
AB  - OBJECTIVES: Roux-en-Y gastric bypass (RYGB) has greater efficacy for weight loss
      in obese patients than gastric banding (BAND) surgery. We hypothesise that this
      may result from different effects on food hedonics via physiological changes
      secondary to distinct gut anatomy manipulations. DESIGN: We used functional MRI,
      eating behaviour and hormonal phenotyping to compare body mass index (BMI)
      matched unoperated controls and patients after RYGB and BAND surgery for obesity.
      RESULTS: Obese patients after RYGB had lower brain-hedonic responses to food than
      patients after BAND surgery. RYGB patients had lower activation than BAND
      patients in brain reward systems, particularly to high-calorie foods, including
      the orbitofrontal cortex, amygdala, caudate nucleus, nucleus accumbens and
      hippocampus. This was associated with lower palatability and appeal of high
      calorie foods and healthier eating behaviour, including less fat intake, in RYGB
      compared with BAND patients and/or BMI-matched unoperated controls. These
      differences were not explicable by differences in hunger or psychological traits
      between the surgical groups, but anorexigenic plasma gut hormones (GLP-1 and
      PYY), plasma bile acids and symptoms of dumping syndrome were increased in RYGB
      patients. CONCLUSIONS: The identification of these differences in food hedonic
      responses as a result of altered gut anatomy/physiology provides a novel
      explanation for the more favourable long-term weight loss seen after RYGB than
      after BAND surgery, highlighting the importance of the gut-brain axis in the
      control of reward-based eating behaviour.

PMID- 23964102
TI  - Pillars Article: the carrier effect in the secondary response to hapten-protein
      conjugates. I. measurement of the effect with transferred cells and objections to
      the local environment hypothesis. Eur. J. Immunol. 1971. 1:10-17.

PMID- 23964103
TI  - Pillars article: the carrier effect in the secondary response to hapten-protein
      conjugates. II. cellular cooperation. Eur. J. Immunol. 1971. 1:18-27.

PMID- 23964104
TI  - Immune dysfunction and bacterial coinfections following influenza.
AB  - Secondary pulmonary infections by encapsulated bacteria including Streptococcus
      pneumoniae and Staphylococcus aureus following influenza represent a common and
      challenging clinical problem. The reasons for this polymicrobial synergy are
      still not completely understood, hampering development of effective prophylactic
      and therapeutic interventions. Although it has been commonly thought that viral
      induced epithelial cell damage allows bacterial invasiveness, recent studies by
      several groups have now implicated dysfunctional innate immune defenses following
      influenza as the primary culprit for enhanced susceptibility to secondary
      bacterial infections. Understanding the immunological imbalances that are
      responsible for virus/bacteria synergy will ultimately allow the design of
      effective, broad-spectrum therapeutic approaches for prevention of enhanced
      susceptibility to these pathogens. 

PMID- 23964105
TI  - Preventive and therapeutic effects of adenanthin on experimental autoimmune
      encephalomyelitis by inhibiting NF-kappaB signaling.
AB  - Adenanthin, a diterpenoid isolated from the leaves of Isodon adenanthus, has been
      reported to possess antileukemic activity through targeting peroxiredoxin I/II.
      However, its other potential activities remain to be explored. Using myelin
      oligodendrocyte glycoprotein (MOG)35-55-induced experimental autoimmune
      encephalomyelitis (EAE), an animal model for multiple sclerosis, we report in
      this study that adenanthin exerts efficaciously preventive and therapeutic
      effects on EAE accompanied by significant restriction of infiltration of
      inflammatory cells and demyelination in CNS. Adenanthin-presented
      immunomodulatory effects on EAE are correlated with suppressed proliferation of
      MOG35-55-reactive T cells, decreased Th1 and Th17 cells, increased regulatory T
      cell populations, decreased production of serum proinflammatory cytokines, and
      reduced stimulatory capacity of APCs, which might be mediated by its inhibitory
      action on NF-kappaB signaling pathway. Our results propose that, as a novel NF
      kappaB inhibitor, adenanthin has potent immunomodulatory activity for the
      treatment of multiple sclerosis and possibly other autoimmune disorders. 

PMID- 23964106
TI  - Virologic correlates of anti-CMV IgG levels in HIV-1-infected men.
AB  - In human immunodeficiency virus (HIV)-infected individuals, higher levels of anti
      cytomegalovirus (CMV) immunoglobulin G (IgG) antibody have been associated with
      increased immune activation, increased HIV transmission, cardiovascular
      complications, and neurocognitive impairment. However, the mechanism of these
      observations is unknown. This analysis of 228 HIV-infected men found that higher
      CMV IgG levels were positively associated with older age and antiretroviral
      treatment. Higher frequency of detectable CMV in peripheral blood mononuclear
      cells and recurrent seminal CMV reactivations were associated with lower plasma
      CMV IgG levels, suggesting that immune response to CMV rather than direct effect
      of viral replication is likely responsible for adverse clinical outcome observed
      in other studies. 

PMID- 23964107
TI  - Variants in HAVCR1 gene region contribute to hepatitis C persistence in African
      Americans.
AB  - To confirm previously identified polymorphisms in HAVCR1 that were associated
      with persistent hepatitis C virus (HCV) infection in individuals of African and
      of European descent, we studied 165 subjects of African descent and 635 subjects
      of European descent. Because the association was only confirmed in subjects of
      African descent (rs6880859; odds ratio, 2.42; P = .01), we then used 379 subjects
      of African descent (142 with spontaneous HCV clearance) to fine-map HAVCR1.
      rs111511318 was strongly associated with HCV persistence after adjusting for
      IL28B and HLA (adjusted P = 8.8 * 10(-4)), as was one 81-kb haplotype (adjusted P
      = .0006). The HAVCR1 genomic region is an independent genetic determinant of HCV
      persistence in individuals of African descent. 

PMID- 23964108
TI  - Schistosomiasis japonica during pregnancy is associated with elevated endotoxin
      levels in maternal and placental compartments.
AB  - Schistosomiasis affects approximately 40 million women of reproductive age and
      has been linked to elevated levels of circulating endotoxin in nonpregnant
      individuals. We have evaluated endotoxin levels in maternal, placental, and
      newborn blood collected from women residing in Leyte, Philippines. Endotoxin
      levels in both maternal and placental compartments in pregnant women with
      schistosomiasis were 1.3- and 2.4-fold higher, respectively, than in uninfected
      women. In addition, higher concentrations of endotoxin in placental blood were
      associated with premature birth, acute chorioamnionitis, and elevated
      proinflammatory cytokines. By promoting endotoxemia, schistosomiasis may exert
      additional, maladaptive influences on pregnancy outcomes. 

PMID- 23964109
TI  - Aging promotes B-1b cell responses to native, but not protein-conjugated,
      pneumococcal polysaccharides: implications for vaccine protection in older
      adults.
AB  - The efficacy of different vaccines in protecting elderly individuals against
      Streptococcus pneumoniae infections is not clear. In the current study, aged mice
      (22-25 months old) exhibited significantly increased susceptibility to
      respiratory infection with serotype 3 S. pneumoniae relative to younger adult
      mice, regardless of whether mice were naive or immunized with native pneumococcal
      polysaccharide (PPS; Pneumovax23) or protein-PPS conjugate (Prevnar-13) vaccines.
      Nonetheless, Pneumovax-immunized aged mice developed limited bacteremia following
      respiratory challenge and exhibited significantly increased survival following
      systemic challenge relative to Prevnar-immune aged mice and young mice that had
      received either vaccine. This was explained by >10-fold increases in PPS-specific
      immunoglobulin G (IgG) levels in Pneumovax-immunized aged mice relative to other
      groups. Remarkably, PPS3-specific B-cell expansion, IgG switching, plasmablast
      differentiation, and spleen and bone marrow antibody-secreting cell frequencies
      were 10-fold higher in aged mice following Pneumovax immunization relative to
      young mice, due to significantly increased B-1b cell participation. In summary,
      this study highlights (1) the need to devise strategies to enhance respiratory
      immunity in aged populations, (2) the diverse responses young and aged
      populations generate to Pneumovax vs Prevnar vaccines, and (3) the potential
      value of exploiting B-1b cell responses in aged individuals for increased vaccine
      efficacy. 

PMID- 23964110
TI  - A shorter time interval between first and second dengue infections is associated
      with protection from clinical illness in a school-based cohort in Thailand.
AB  - BACKGROUND: Despite the strong association between secondary dengue virus (DENV)
      infections and dengue hemorrhagic fever (DHF), the majority of secondary
      infections are subclinical or mild. The determinants of clinical severity remain
      unclear, though studies indicate a titer-dependent and time-dependent role of
      cross-protective anti-DENV antibodies. METHODS: Data from 2 sequential
      prospective cohort studies were analyzed for subclinical and symptomatic DENV
      infections in schoolchildren in Kamphaeng Phet, Thailand (1998-2002 and 2004
      2007). Children experiencing >= 1 DENV infection were selected as the population
      for analysis (contributing 2169 person-years of follow-up). RESULTS: In total,
      1696 children had >= 1 DENV infection detected during their enrollment; 268
      experienced 2 or more infections. A shorter time interval between infections was
      associated with subclinical infection in children seronegative for DENV at
      enrollment, for whom a second-detected DENV infection is more likely to reflect a
      true second infection (average of 2.6 years between infections for DHF, 1.9 for
      DF, and 1.6 for subclinical infections). CONCLUSIONS: These findings support a
      pathogenesis model where cross-reactive antibodies wane from higher-titer,
      protective levels to lower-titer, detrimental levels. This is one of the first
      studies of human subjects to suggest a window of cross-protection following DENV
      infection since Sabin's challenge studies in the 1940s.

PMID- 23964111
TI  - Influence of polyproline region and macro domain genetic heterogeneity on HEV
      persistence in immunocompromised patients.
AB  - Hepatitis E virus (HEV) can chronically infect immunocompromised patients. The
      polyproline region (PPR) and the macro domain of ORF1 protein may modulate virus
      production and/or the host immune response. We investigated the association
      between the genetic heterogeneity of HEV quasispecies in ORF1 and the outcome of
      infection in solid-organ transplant patients. Both sequence entropy and genetic
      distances during the hepatitis E acute phase were higher in patients whose
      infection became chronic than in those who cleared the virus. Hence, great
      quasispecies heterogeneity in the regions encoding the PPR and the macro domain
      may facilitate HEV persistence. 

PMID- 23964112
TI  - Therapeutic strategies for well-differentiated papillary mesothelioma of the
      peritoneum.
AB  - OBJECTIVE: Well-differentiated papillary mesothelioma is an uncommon subtype of
      mesothelioma with a frequently indolent course, although it occasionally
      manifests in a more aggressive form. To establish a treatment strategy for this
      rare disease, we report the clinical characteristics and outcomes of 15 patients
      with well-differentiated papillary mesothelioma. METHODS: All pathologically
      diagnosed well-differentiated papillary mesothelioma cases were reviewed between
      1998 and 2012. RESULTS: Of the 15 cases, 8 and 7 presented with single and
      multiple lesions, respectively. All cases with single lesions were asymptomatic,
      while 4 out of the 7 cases with multiple lesions were symptomatic. After tumor
      excision, none of the eight single-lesion cases experienced tumor recurrence.
      Among the other seven cases with multiple lesions, only one patient with
      disseminated lesions died due to disease burden. Five patients with multiple
      lesions received cisplatin-based intravenous or intraperitoneal chemotherapy,
      with a mix of complete (n= 2) and partial (n= 2) responses observed. Of
      particular note, one patient receiving cisplatin and pemetrexed combination
      chemotherapy experienced complete tumor resolution without any serious toxicity.
      CONCLUSIONS: We recommend different treatment strategies based on the disease
      status. If the tumor is completely resectable, an excisional biopsy seems to be
      sufficient. If complete resection is unavailable for the asymptomatic patient
      with a localized tumor extent, close follow-up is an appropriate option. When the
      tumor is extensive or accompanied by symptoms, chemotherapy should be strongly
      considered.

PMID- 23964113
TI  - Antibody-drug conjugates.

PMID- 23964115
TI  - Extrinsic and intrinsic control of macrophage inflammatory responses.
AB  - Macrophages make major contributions to inflammatory immunopathology. In this
      work, we examine three disease scenarios, in which M1s play a major role early in
      the disease but eventually transitions into a population of cells with
      immunoregulatory activity. We propose that the transition from an inflammatory to
      a regulatory phenotype is a natural progression that regularly occurs in
      stimulated macrophages and that the timing of this transition is critical to
      maintaining homeostasis. In the first section of this review, we discuss the
      exogenous microenvironmental cues that may induce macrophages to enter a
      regulatory state. In the second half of this review, we discuss a novel
      mechanism, whereby TLR-stimulated macrophages can intrinsically induce their own
      regulatory activation state. They do so by secreting and synthesizing endogenous
      "reprogramming" signals that work in an autocrine fashion to promote a regulatory
      phenotype. We propose that these endogenous regulatory mechanisms exist to
      prevent macrophage-mediated immunopathology. Thus, macrophages can respond to
      endogenous and exogenous cues to regulate their activation state, and without
      these controlled regulatory responses, M1 would persist to the detriment of the
      host. 

PMID- 23964117
TI  - Lipoteichoic acid of Enterococcus faecalis induces the expression of chemokines
      via TLR2 and PAFR signaling pathways.
AB  - Enterococcus faecalis is one of the most common opportunistic pathogens
      responsible for nosocomial infections, and its LTA is known as an important
      virulence factor causing inflammatory responses. As chemokines play a key role in
      inflammatory diseases by triggering leukocyte infiltration into the infection
      site, we purified EfLTA and investigated its effect on the expression of
      chemokines, IP-10, MIP-1alpha, and MCP-1, in murine macrophages. EfLTA induced
      the expression of these chemokines at the mRNA and protein levels. TLR2, CD14,
      and MyD88 were involved in the EfLTA-induced chemokine expression, as the
      expression was reduced remarkably in macrophages derived from TLR2-, CD14-, or
      MyD88-deficient mice. EfLTA induced phosphorylation of MAPKs and enhanced the DNA
      binding activity of NF-kappaB, AP-1, and NF-IL6 transcription factors. The
      induction of IP-10 required ERK, JNK, p38 MAPK, PKC, PTK, PI3K, and ROS. We
      noticed that all of these signaling molecules, except p38 MAPK and ROS, were
      indispensable for the induction of MCP-1 and MIP-1alpha. Interestingly, the EfLTA
      induced chemokine expression was mediated through PAFR/JAK/STAT1 signaling
      pathways without IFN-beta involvement, which is different from LPS-induced
      chemokine expression requiring IFN-beta/JAK/STAT1 signaling pathways.
      Furthermore, the culture supernatant of EfLTA-treated RAW 264.7 cells promoted
      the platelet aggregation, and exogenous PAF induced the chemokine expression in
      macrophages derived from WT and TLR2-deficient mice. These results suggest that
      EfLTA induces the expression of chemokines via signaling pathways requiring TLR2
      and PAFR, which is distinct from that of LPS-induced chemokine expression. 

PMID- 23964116
TI  - Oxygen levels determine the ability of glucocorticoids to influence neutrophil
      survival in inflammatory environments.
AB  - GCs are highly effective in treating a wide range of inflammatory diseases but
      are limited in their ability to control neutrophilic lung inflammation in
      conditions such as COPD. Neutrophil apoptosis, a central feature of inflammation
      resolution, is delayed in response to microenvironmental cues, such as hypoxia
      and inflammatory cytokines, present at inflamed sites. GCs delay neutrophil
      apoptosis in vitro, and this may therefore limit the ability of GCs to control
      neutrophilic inflammation. This study assesses the effect GCs have on hypoxia-
      and inflammatory cytokine-induced neutrophil survival. Human neutrophils were
      treated with GCs in the presence or absence of GM-CSF or inflammatory macrophage
      CM at a range of oxygen concentrations (21-1% oxygen). Neutrophil apoptosis and
      survival were assessed by flow cytometry and morphological analysis and
      neutrophil function, by stimulus-induced shape change and respiratory burst.
      Dexamethasone promoted neutrophil survival at 21%, 10%, and 5% oxygen but not at
      1% oxygen. Interestingly, GM-CSF and inflammatory CM increased neutrophil
      survival significantly, even at 1% oxygen, with cells remaining functionally
      active at 96 h. Dexamethasone was able to reduce the prosurvival effect of GM-CSF
      and inflammatory CM in a hypoxic environment. In conclusion, we found that GCs do
      not augment neutrophil survival in the presence of severe hypoxia or
      proinflammatory mediators. This suggests that GCs would not promote neutrophil
      survival at sites of inflammation under these conditions. 

PMID- 23964119
TI  - Distinct development and functions of resident and recruited liver Kupffer
      cells/macrophages.
AB  - Although mouse liver F4/80(+) Kupffer cells consist of cytokine-producing
      CD11b(+) cells and phagocytic CD68(+) cells, an undefined CD11b(-) CD68(-) subset
      (30%) also exists. We herein demonstrate a more fundamental classification by
      adding CD32 (FcgammaRII), which covers most liver F4/80(+) cells and the distinct
      functions of them. Among the F4/80(+) cells, 50%, 40%, and 30% of cells were
      CD32(+), CD68(+), and CD11b(+), respectively, and one-half of the CD68(+) cells
      coexpressed CD32. CD68(+) and CD32(+) cells, but not CD11b(+) cells, expressed a
      phagocytosis-related CRIg. Gy (6) irradiation depleted liver CD11b(+) cells and
      those in the spleen, bone marrow, and peripheral blood but not liver CD32/CD68(+)
      cells. Transfer of bone marrow cells into the irradiated mice reconstituted liver
      CD11b(+) cells. Conversely, clodronate pretreatment depleted only liver
      CD32/CD68(+) cells but not liver CD11b(+) cells and peripheral blood or spleen
      CD11b(+) monocytes/macrophages. Moreover, the CD32(+) cells might be precursors
      of CD68(+) cells, as a large proportion of CD32(+) cells expressed the c-kit
      (CD117), and CD34 and CD32(+) cells acquired CD68 immediately after bacteria
      administration. CD32/CD68(+) cells, but not CD11b(+) cells, expressed resident
      macrophage-specific MerTK and CD64 (FcgammaRI). Challenge with Staphylococcus
      aureus or liver metastatic EL-4 tumor cells indicated that the CD68(+) subset is
      engaged in systemic bactericidal activity, whereas the CD11b(+) subset is pivotal
      for liver antitumor immunity. Human liver CD14(+) Kupffer cells could also be
      classified into three similar subsets. These results suggest that liver CD68(+)
      Kupffer cells and CD11b(+) Kupffer cells/macrophages are developmentally and
      functionally distinct subsets. 

PMID- 23964118
TI  - MMP28 promotes macrophage polarization toward M2 cells and augments pulmonary
      fibrosis.
AB  - Members of the MMP family function in various processes of innate immunity,
      particularly in controlling important steps in leukocyte trafficking and
      activation. MMP28 (epilysin) is a member of this family of proteinases, and we
      have found that MMP28 is expressed by macrophages and regulates their recruitment
      to the lung. We hypothesized that MMP28 regulates other key macrophage responses,
      such as macrophage polarization. Furthermore, we hypothesized that these MMP28
      dependent changes in macrophage polarization would alter fibrotic responses in
      the lung. We examined the gene expression changes in WT and Mmp28-/- BMDMs,
      stimulated with LPS or IL-4/IL-13 to promote M1 and M2 cells, respectively. We
      also collected macrophages from the lungs of Pseudomonas aeruginosa-exposed WT
      and Mmp28-/- mice to evaluate changes in macrophage polarization. Lastly, we
      evaluated the macrophage polarization phenotypes during bleomycin-induced
      pulmonary fibrosis in WT and Mmp28-/- mice and assessed mice for differences in
      weight loss and total collagen levels. We found that MMP28 dampens
      proinflammatory macrophage function and promots M2 programming. In both in vivo
      models, we found deficits in M2 polarization in Mmp28-/- mice. In bleomycin
      induced lung injury, these changes were associated with reduced fibrosis. MMP28
      is an important regulator of macrophage polarization, promoting M2 function. Loss
      of MMP28 results in reduced M2 polarization and protection from bleomycin-induced
      fibrosis. These findings highlight a novel role for MMP28 in macrophage biology
      and pulmonary disease. 

PMID- 23964120
TI  - CD36 deletion reduces VLDL secretion, modulates liver prostaglandins, and
      exacerbates hepatic steatosis in ob/ob mice.
AB  - Recent findings described the role of CD36-mediated signaling in regulating
      cellular calcium and the release of various bioactive molecules, including the
      prostaglandins, neurotransmitters, cholecystokinin, and secretin. Here we
      document the role of CD36 in the secretion of hepatic VLDL. CD36 deletion
      resulted in 60% suppression of VLDL output in vivo, and VLDL secretion was
      reduced in vitro using incubated liver slices. The effect of CD36 deletion was
      mediated by enhancing formation of hepatic prostaglandins D2, F2, and E2.
      Treatment of CD36-deficient slices with inhibitors of cyclooxygenases reversed
      the reduction in triglyceride secretion. We also examined the effect of CD36
      deletion on the obesity-associated spontaneous steatosis of the ob/ob mouse that
      is driven by enhanced de novo lipogenesis. Homozygous ob/ob mice lacking CD36 (ob
      CD36-/-) were generated and studied for hepatic triglyceride accumulation and
      VLDL secretion. Livers of ob/ob mice were steatotic as expected and had 5-fold
      more CD36 on Kupffer cells and hepatocytes. CD36 deletion exacerbated the
      steatosis by impairing hepatic triglyceride and apoB secretion through increasing
      prostaglandin levels. These findings suggest an unappreciated role of CD36 in
      regulating VLDL secretion, which might have relevance to some forms of fatty
      liver. They provide insight into the association reported in humans between CD36
      protein expression and serum levels of apoB and VLDL particle number.

PMID- 23964121
TI  - Association between cholesterol synthesis/absorption markers and effects of
      cholesterol lowering by atorvastatin among patients with high risk of coronary
      heart disease.
AB  - No indices are currently available to facilitate clinicians to identify patients
      who need either statin monotherapy or statin-ezetimibe combined treatment. We
      aimed to investigate whether cholesterol synthesis and absorption markers can
      predict the cholesterol-lowering response to statin. Total 306 statin-naive
      patients with high risk of coronary heart disease (CHD) were treated with
      atorvastatin 20 mg/day for 1 month. Cholesterol synthesis and absorption markers
      and LDL cholesterol (LDL-C) levels were measured before and after treatment.
      Atorvastatin decreased LDL-C by 36.8% (range: decrease of 74.5% to increase of
      31.9%). Baseline cholesterol synthesis marker lathosterol and cholesterol
      absorption marker campesterol codetermined the effect of atorvastatin treatment.
      The effect of cholesterol lowering by atorvastatin was significantly associated
      with baseline lathosterol levels but modified bidirectionally by baseline
      campesterol levels. In patients with the highest baseline campesterol levels,
      atorvastatin treatment decreased cholesterol absorption by 46.1%, which enhanced
      the effect of LDL-C lowering. Atorvastatin treatment increased cholesterol
      absorption by 52.3% in those with the lowest baseline campesterol levels, which
      attenuated the effect of LDL-C reduction. Especially those with the highest
      lathosterol but the lowest campesterol levels at baseline had significantly less
      LDL-C reduction than those with the same baseline lathosterol levels but the
      highest campesterol levels (27.3% versus 42.4%, P = 0.002). These results suggest
      that combined patterns of cholesterol synthesis/absorption markers, rather than
      each single marker, are potential predictors of the LDL-C-lowering effects of
      atorvastatin in high-risk CHD patients. 

PMID- 23964122
TI  - Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors.
AB  - CD73 inhibits antitumor immunity through the activation of adenosine receptors
      expressed on multiple immune subsets. CD73 also enhances tumor metastasis,
      although the nature of the immune subsets and adenosine receptor subtypes
      involved in this process are largely unknown. In this study, we revealed that
      A2A/A2B receptor antagonists were effective in reducing the metastasis of tumors
      expressing CD73 endogenously (4T1.2 breast tumors) and when CD73 was ectopically
      expressed (B16F10 melanoma). A2A(-/-) mice were strongly protected against tumor
      metastasis, indicating that host A2A receptors enhanced tumor metastasis. A2A
      blockade enhanced natural killer (NK) cell maturation and cytotoxic function in
      vitro, reduced metastasis in a perforin-dependent manner, and enhanced NK cell
      expression of granzyme B in vivo, strongly suggesting that the antimetastatic
      effect of A2A blockade was due to enhanced NK cell function. Interestingly, A2B
      blockade had no effect on NK cell cytotoxicity, indicating that an NK cell
      independent mechanism also contributed to the increased metastasis of CD73(+)
      tumors. Our results thus revealed that CD73 promotes tumor metastasis through
      multiple mechanisms, including suppression of NK cell function. Furthermore, our
      data strongly suggest that A2A or A2B antagonists may be useful for the treatment
      of metastatic disease. Overall, our study has potential therapeutic implications
      given that A2A/A2B receptor antagonists have already entered clinical trials in
      other therapeutic settings. 

PMID- 23964123
TI  - NR2B subunit of the NMDA glutamate receptor regulates appetite in the
      parabrachial nucleus.
AB  - Diphtheria toxin-mediated, acute ablation of hypothalamic neurons expressing
      agouti-related protein (AgRP) in adult mice leads to anorexia and starvation
      within 7 d that is caused by hyperactivity of neurons within the parabrachial
      nucleus (PBN). Because NMDA glutamate receptors are involved in various synaptic
      plasticity-based behavioral modifications, we hypothesized that modulation of the
      NR2A and NR2B subunits of the NMDA receptor in PBN neurons could contribute to
      the anorexia phenotype. We observed by Western blot analyses that ablation of
      AgRP neurons results in enhanced expression of NR2B along with a modest
      suppression of NR2A. Interestingly, systemic administration of LiCl in a critical
      time window before AgRP neuron ablation abolished the anorectic response. LiCl
      treatment suppressed NR2B levels in the PBN and ameliorated the local Fos
      induction that is associated with anorexia. This protective role of LiCl on
      feeding was blunted in vagotomized mice. Chronic infusion of RO25-6981, a
      selective NR2B inhibitor, into the PBN recapitulated the role of LiCl in
      maintaining feeding after AgRP neuron ablation. We suggest that the accumulation
      of NR2B subunits in the PBN contributes to aphagia in response to AgRP neuron
      ablation and may be involved in other forms of anorexia. 

PMID- 23964124
TI  - Surface chemistry allows for abiotic precipitation of dolomite at low
      temperature.
AB  - Although the mineral dolomite is abundant in ancient low-temperature sedimentary
      systems, it is scarce in modern systems below 50  degrees C. Chemical
      mechanism(s) enhancing its formation remain an enigma because abiotic dolomite
      has been challenging to synthesize at low temperature in laboratory settings.
      Microbial enhancement of dolomite precipitation at low temperature has been
      reported; however, it is still unclear exactly how microorganisms influence
      reaction kinetics. Here we document the abiotic synthesis of low-temperature
      dolomite in laboratory experiments and constrain possible mechanisms for dolomite
      formation. Ancient and modern seawater solution compositions, with identical pH
      and pCO2, were used to precipitate an ordered, stoichiometric dolomite phase at
      30  degrees C in as few as 20 d. Mg-rich phases nucleate exclusively on
      carboxylated polystyrene spheres along with calcite, whereas aragonite forms in
      solution via homogeneous nucleation. We infer that Mg ions are complexed and
      dewatered by surface-bound carboxyl groups, thus decreasing the energy required
      for carbonation. These results indicate that natural surfaces, including organic
      matter and microbial biomass, possessing a high density of carboxyl groups may be
      a mechanism by which ordered dolomite nuclei form. Although environments rich in
      organic matter may be of interest, our data suggest that sharp biogeochemical
      interfaces that promote microbial death, as well as those with high salinity may,
      in part, control carboxyl-group density on organic carbon surfaces, consistent
      with origin of dolomites from microbial biofilms, as well as hypersaline and
      mixing zone environments. 

PMID- 23964126
TI  - The growth speed of microtubules with XMAP215-coated beads coupled to their ends
      is increased by tensile force.
AB  - The generation of pulling and pushing forces is one of the important functions of
      microtubules, which are dynamic and polarized structures. The ends of dynamic
      microtubules are able to form relatively stable links to cellular structures, so
      that when a microtubule grows it can exert a pushing force and when it shrinks it
      can exert a pulling force. Microtubule growth and shrinkage are tightly regulated
      by microtubule-associated proteins (MAPs) that bind to microtubule ends. Given
      their localization, MAPs may be exposed to compressive and tensile forces. The
      effect of such forces on MAP function, however, is poorly understood. Here we
      show that beads coated with the microtubule polymerizing protein XMAP215, the
      Xenopus homolog of Dis1 and chTOG, are able to link stably to the plus ends of
      microtubules, even when the ends are growing or shrinking; at growing ends, the
      beads increase the polymerization rate. Using optical tweezers, we found that
      tensile force further increased the microtubule polymerization rate. These
      results show that physical forces can regulate the activity of MAPs. Furthermore,
      our results show that XMAP215 can be used as a handle to sense and mechanically
      manipulate the dynamics of the microtubule tip. 

PMID- 23964131
TI  - Fellowships in international emergency medicine in the USA: a comparative survey
      of program directors' and fellows' perspectives on the curriculum.
AB  - OBJECTIVE: Experts have proposed core curriculum components for international
      emergency medicine (IEM) fellowships. This study examined perceptions of program
      directors (PDs) and fellows on whether IEM fellowships cover these components,
      whether their perspectives differ and the barriers preventing fellowships from
      covering them. METHODS: From 1 November 2011 to 30 November 2011, a survey was
      administered to PDs, current fellows and recent graduates of the 34 US IEM
      fellowships. Respondents quantified their fellowship experience in six proposed
      core curriculum areas: emergency medicine (EM) systems development, EM education,
      humanitarian assistance, public health, emergency medical services and disaster
      medicine. Analysis was performed regarding what per cent of programmes fulfil the
      six curriculum areas. A paired t test determined the difference between PDs' and
      fellows' responses. Agreement between PDs and fellows within the same programme
      was determined using a kappa statistic. RESULTS: Only 1/18 (6%) (according to
      fellows) to 2/24 (8%) (according to PDs) of programmes expose fellows to all six
      components. PDs consistently reported higher exposure than fellows. The
      difference in mean score between PDs and fellows was statistically significant
      (p<0.05) in three of the 6 (50%) core curriculum elements: humanitarian aid,
      public health and disaster medicine. Per cent agreement between PDs and fellows
      within each programmes ranged from poor to fair. CONCLUSIONS: While IEM
      fellowships have varying structure, this study highlights the importance of
      further discussion between PDs and fellows regarding delineation and objectives
      of core curriculum components. Transparent curricula and open communication
      between PDs and fellows may reduce differences in reported experiences.

PMID- 23964128
TI  - Axial interactions in the mixed-valent CuA active site and role of the axial
      methionine in electron transfer.
AB  - Within Cu-containing electron transfer active sites, the role of the axial ligand
      in type 1 sites is well defined, yet its role in the binuclear mixed-valent CuA
      sites is less clear. Recently, the mutation of the axial Met to Leu in a CuA site
      engineered into azurin (CuA Az) was found to have a limited effect on E(0)
      relative to this mutation in blue copper (BC). Detailed low-temperature
      absorption and magnetic circular dichroism, resonance Raman, and electron
      paramagnetic resonance studies on CuA Az (WT) and its M123X (X = Q, L, H) axial
      ligand variants indicated stronger axial ligation in M123L/H. Spectroscopically
      validated density functional theory calculations show that the smaller DeltaE(0)
      is attributed to H2O coordination to the Cu center in the M123L mutant in CuA but
      not in the equivalent BC variant. The comparable stabilization energy of the
      oxidized over the reduced state in CuA and BC (CuA ~ 180 mV; BC ~ 250 mV)
      indicates that the S(Met) influences E(0) similarly in both. Electron
      delocalization over two Cu centers in CuA was found to minimize the Jahn-Teller
      distortion induced by the axial Met ligand and lower the inner-sphere
      reorganization energy. The Cu-S(Met) bond in oxidized CuA is weak (5.2 kcal/mol)
      but energetically similar to that of BC, which demonstrates that the protein
      matrix also serves an entatic role in keeping the Met bound to the active site to
      tune down E(0) while maintaining a low reorganization energy required for rapid
      electron transfer under physiological conditions. 

PMID- 23964132
TI  - Precision medicine for cancer patients: lessons learned and the path forward.

PMID- 23964134
TI  - Magnetic-resonance imaging of the human brain with an atomic magnetometer.
AB  - Magnetic resonance imaging (MRI) is conventionally performed in very high fields,
      and this leads to some restrictions in applications. To remove such restrictions,
      the ultra-low field MRI approach has been proposed. Because of the loss of
      sensitivity, the detection methods based on superconducting quantum interference
      devices (SQUIDs) in a shielded room were used. Atomic magnetometers have similar
      sensitivity as SQUIDs and can also be used for MRI, but there are some technical
      difficulties to overcome. We demonstrate that MRI of the human brain can be
      obtained with an atomic magnetometer with in-plane resolution of 3 mm in 13 min.

PMID- 23964133
TI  - Independent validation of a model using cell line chemosensitivity to predict
      response to therapy.
AB  - BACKGROUND: Methods using cell line microarray and drug sensitivity data to
      predict patients' chemotherapy response are appealing, but groups may be
      reluctant to release details to preserve intellectual property. Here we describe
      a case study to validate predictions while treating the methods as a "black box."
      METHODS: Medical Prognosis Institute (MPI) constructed cell-line-derived
      sensitivity scores (SSs) and combined scores (CSs) that incorporate clinical
      variables. MD Anderson researchers evaluated their predictions. We searched the
      Gene Expression Omnibus (GEO) to identify validation datasets, and we performed
      statistical evaluation of the agreement between prediction and clinical
      observation. RESULTS: We identified 3 suitable datasets: GSE16446 (n = 120;
      binary outcome), GSE17920 (n = 130; binary outcome), and GSE10255 (n = 161;
      continuous and time-to-event outcomes). The SS was statistically significantly
      associated with primary treatment responses for all studies (GSE16446: P = .02;
      GSE17920: P = .02; GSE10255: P = .02). Dichotomized SSs performed no better than
      chance for GSE16446 and GSE17920, and categorized SSs did not predict disease
      free survival (GSE10255). SSs sometimes improved on predictions using clinical
      variables (GSE16446: P = .05; GSE17920: P = .31; GSE10255: P = .045), but gains
      were limited (95% confidence intervals for GSE16446 and GSE17920 include 0). The
      CS did not predict treatment response for GSE16446 (P = .55), but it did for
      GSE17920 (P < .001). Coefficients of clinical variables provided by MPI for CSs
      agree with estimates for GSE17920 better than estimates for GSE16446.
      CONCLUSIONS: Model predictions were better than chance in all three datasets.
      However, these scores added little to existing clinical predictors; statistically
      significant contributions were likely to be too small to change clinical
      practice. These findings suggest that discovering better predictors will require
      both cell line data and a clinical training dataset of patient samples.

PMID- 23964135
TI  - Protein adsorption enhanced radio-frequency heating of silica nanoparticles.
AB  - Measurements of specific-absorption-rate (SAR) of silica 30, 50, and 100 nm
      nanoparticles (NP) suspended in water were carried out at 30 MHz in 7 kV/m radio
      frequency (rf) electric field. Size dependent, NP-suspension interface related
      heating of silica NP was observed. To investigate a possible mechanism of
      heating, bovine serum albumin was adsorbed on the surface of silica NPs in
      suspension. It resulted in significant enhancement of SAR when compared to bare
      silica NPs. A calorimetric and rf loss model was used to calculate effective
      conductivity of silica NP with/without adsorbed albumin as a function of silica
      size and albumin concentration.

PMID- 23964136
TI  - Ursodeoxycholic acid therapy in gallbladder disease, a story not yet completed.
AB  - Gallstone disease represents an important issue in the healthcare system. The
      principal non-invasive non-surgical medical treatment for cholesterol gallstones
      is still represented by oral litholysis with bile acids. The first successful and
      documented dissolution of cholesterol gallstones was achieved in 1972. Since then
      a large number of investigators all over the world, have been dedicated in
      biochemical and clinical studies on ursodeoxycholic acid (UDCA), demonstrating
      its extreme versatility. This editorial is aimed to provide a brief review of
      recent developments in UDCA use, current indications for its use and, the more
      recent advances in understanding its effects in terms of an anti-inflammatory
      drug. 

PMID- 23964138
TI  - Role of bevacizumab in colorectal cancer growth and its adverse effects: a
      review.
AB  - Angiogenesis affects both wound healing and malignant cell growth through
      nutrients and oxygen. Vascular endothelial growth factor (VEGF) is the most
      important element involved in this complex process. Inhibition of VEGF influences
      angiogenesis and may restrict tumor growth and metastatic ability. Modern anti
      angiogenic therapy is based on this theory. Bevacizumab is a recombinant
      humanized monoclonal antibody (immunoglobulin G1) which binds with VEGF-A forming
      a large molecule. It can not be bound with VEGF tyrosine kinase receptors
      preventing VEGF-A incorporation; thus its activity is inhibited inducing blockage
      of VEGF-mediated angiogenesis. Bevacizumab, in combination with chemotherapy or
      other novel targeted therapeutic agents, is currently used more frequently in
      clinical practice, mainly for managing advanced colorectal cancer. It is also
      used for managing other malignancies, such as breast cancer, pancreatic cancer,
      prostate cancer, non small-cell lung cancer, metastatic renal carcinoma and
      ovarian tumors. Although it is generally considered a safe treatment, there are
      reports of some rare side effects which should be taken into account. Recent
      experiments in rats and mice show promising results with a wider therapeutic
      range. 

PMID- 23964139
TI  - Eosinophilic gastroenteritis: an unusual type of gastroenteritis.
AB  - Eosinophilic gastroenteritis (EGE) is a rare disorder characterized by
      eosinophilic infiltration of the bowel wall with various gastrointestinal
      manifestations. Till date only 280 cases have been described in the literature. A
      high index of suspicion, by excluding other causes of peripheral eosinophilia, is
      a pre requisite for accurate diagnosis. EGE is an uncommon gastrointestinal
      disease affecting both children and adults. It was first described by Kaijser in
      1937. Presentation may vary depending on location as well as depth and extent of
      bowel wall involvement and usually runs a chronic relapsing course. This
      condition can respond to low dose steroid therapy, thereby preventing grave
      complications like ascites and intestinal obstruction that might need surgical
      intervention. The natural history of EGE has not been well documented.
      Eosinophilic gastroenteritis is a chronic, waxing and waning condition. Mild and
      sporadic symptoms can be managed with reassurance and observation, whereas
      disabling gastrointestinal (GI) symptom flare-ups can often be controlled with
      oral corticosteroids. When the disease manifests in infancy and specific food
      sensitization can be identified, the likelihood of disease remission by late
      childhood is high. GI obstruction is the most common complication. Fatal outcomes
      are rare. 

PMID- 23964137
TI  - Portal hypertension and gastrointestinal bleeding: diagnosis, prevention and
      management.
AB  - Bleeding from esophageal varices is a life threatening complication of portal
      hypertension. Primary prevention of bleeding in patients at risk for a first
      bleeding episode is therefore a major goal. Medical prophylaxis consists of non
      selective beta-blockers like propranolol or carvedilol. Variceal endoscopic band
      ligation is equally effective but procedure related morbidity is a drawback of
      the method. Therapy of acute bleeding is based on three strategies: vasopressor
      drugs like terlipressin, antibiotics and endoscopic therapy. In refractory
      bleeding, self-expandable stents offer an option for bridging to definite
      treatments like transjugular intrahepatic portosystemic shunt (TIPS). Treatment
      of bleeding from gastric varices depends on vasopressor drugs and on injection of
      varices with cyanoacrylate. Strategies for primary or secondary prevention are
      based on non-selective beta-blockers but data from large clinical trials is
      lacking. Therapy of refractory bleeding relies on shunt-procedures like TIPS.
      Bleeding from ectopic varices, portal hypertensive gastropathy and gastric antral
      vascular ectasia-syndrome is less common. Possible medical and endoscopic
      treatment options are discussed. 

PMID- 23964140
TI  - Serum proteins in chronic hepatitis B patients treated with peginterferon alfa
      2b.
AB  - AIM: To study the differential protein profile in serum of hepatitis B patients.
      METHODS: Serum samples were obtained from patients with chronic hepatitis B who
      were receiving peginterferon alfa-2b. The serum samples were subjected to albumin
      depletion and analyzed by two-dimensional gel electrophoresis (2-DE).
      Differentially expressed protein spots were identified by electrospray ionization
      quadrupole time-of-flight mass spectrometry. Alpha-2-HS-glycoprotein, complement
      component C3c and CD5 antigen were further analyzed by an enzyme-linked
      immunosorbent assay and immunonephelometry. RESULTS: Nineteen patients with HBeAg
      positive chronic hepatitis B (CHB) were studied. These patients were followed for
      at least 1 year after treatment and were classified according to their treatment
      response: responders (n = 9) and non-responders (n = 10). 2-DE and MS/MS analysis
      were performed to compare the serum proteins before initiating peginterferon alfa
      2b. From the quantitative analysis of the 2-D gel, 7 proteins were detected
      between the two groups at different levels before treatment. Among these
      potential candidates, serum levels of alpha-2-HS-glycoprotein, complement
      component C3c and CD5 antigen-like precursor were further analyzed. In the
      validation phase, 23 subjects, 9 sustained responders and 14 non-responders, were
      recruited. Interestingly, the levels of alpha-2-HS-glycoprotein and complement
      component C3c were elevated in the serum of the non-responders compared to the
      responders. CONCLUSION: Serum alpha-2-HS-glycoprotein and complement component
      C3c may be potential serum biomarkers in predicting the treatment response of
      peginterferon alfa-2b in patients with CHB prior to treatment.

PMID- 23964141
TI  - Impact of mesocaval shunt on safe minimal liver remnant: porcine model.
AB  - AIM: To investigate the capacity of shunts to relieve portal hypertension and
      decrease the safe minimal liver remnant in pigs. METHODS: A subtotal hepatectomy
      with < 60 mL blood loss and without hepatic pedicle occlusion was performed. The
      mesenteric venous inflow was diverted through a mesocaval shunt (MCS) constructed
      using the prepared left renal vein with an end-to-side running suture of 5-0
      proline. All 21 animals that underwent subtotal hepatectomy and/or MCS were
      divided into three groups. In the 15% group, the residual volume was 14%-19% of
      total liver volume (TLV); in the 15%+ S group, the residual volume was also 14%
      19% of TLV with a mesocaval shunt (MCS); and in the 10%+ S group, the residual
      volume was 8%-13% of TLV with an MCS. In the three groups, the intraoperative
      portal vein pressure (PVP) and portal vein flow (PVF) were monitored and compared
      at laparotomy and 1 h post-hepatectomy. The survival rate, sinusoidal endothelial
      damage, tissue analysis, and serum analysis were investigated among the three
      groups. RESULTS: The percentage residual liver volume was 15.9%, 16.1% and 11.8%
      in the 15%, 15%+ S, 10%+ S groups, respectively. After hepatectomy, PVF and
      portal-to-arterial flow ratio in the 15%+ S group significantly decreased and
      hepatic artery flow (HAF) per unit volume significantly increased, compared to
      those in the 15% group. The PVP in the 15%+ S group and 10%+ S group increased
      slightly from that measured at laparotomy; however, in the 15% group, the PVP
      increased immediately and significantly above that observed in the other two
      groups. The 14-d survival rates were 28.5%, 85.6%, and 14.2% in the 15%, 15%+ S,
      and 10%+ S groups, respectively. In the 15%+ S group, the shunts effectively
      attenuated injury to the sinusoidal endothelium, and the changes in the serum and
      tissue analysis results were significantly reduced compared to those in the 15%
      and 10%+ S groups. CONCLUSION: MCS can decompress the portal vein and so
      attenuate liver injury from hyperperfusion, and make extreme or marginal
      hepatectomy safer.

PMID- 23964142
TI  - Effects of radix curcumae-derived diterpenoid C on Helicobacter pylori-induced
      inflammation and nuclear factor kappa B signal pathways.
AB  - AIM: To study effect of diterpenoid C extracted from radix curcumae on
      Helicobacter pylori (H. pylori)-infected inflammation, intestinal metaplasia, and
      nuclear factor kappa B (NF-kappaB) signaling pathway in vitro. METHODS: We used I
      type H. pylori to infect human gastric epithelial gastric epithelium cell line
      (GES-1) cell lines, and then H. pylori-infected GES-1 cells were treated with
      radix curcumae (RC)-derived diterpenoid C of different concentrations (5, 10, 20
      MUg/mL) and amoxicillin. The expression of p65, IkappaB kinase (IKK) alpha and
      IKKgamma proteins was detected with Western blotting, and the expression of
      interleukin (IL)-8, IL-6 and IL-4 was determined with enzyme-linked immunosorbent
      assay method. Data were analyzed using SPSS software ver18.0. For comparisons
      between groups of more than two unpaired values, one-way analysis of variance
      (ANOVA) was used. If an ANOVA F value was significant, post hoc comparisons were
      performed between groups. If results were not normally distributed, the Mann
      Whitney U test was used to compare two groups of unpaired values, whereas for
      comparisons between groups of more than two unpaired values, the Kruskal-Wallis H
      test was used. Statistical significance was established at P < 0.05. RESULTS: The
      MTT assay results revealed the inhibited rate of GES-1, and indicated that the
      IC5 of RC-derived diterpenoid C and amoxicillin all were 5 MUg/mL for gastric GES
      1 cells. The expression of IL-8 was significantly increased, especially at 12 h
      time point; and the expression of IL-4 was decreased in H. pylori-infected GES-1
      cells. After H. pylori-infected GES-1 cells were treated with RC-derived
      diterpenoid C of different concentrations and amoxicillin, the expression of IL-8
      was decreased at 12, 24, 48, 72 h points (P < 0.01), especially in high
      concentration diterpenoid C (20 MUg/mL) group; and the expression of IL-4 was
      increased, especially in moderate and high-concentration diterpenoid C (10 and 20
      MUg/mL) groups. RC-derived diterpenoid C had the inhibitory effects on H. pylori
      induced p65 translocation from cytoplasm into cell nucleus, H. pylori-stimulant
      IkBalpha degradation, the phosphorylation of p65 and IkBalpha, and the expression
      of IKKalpha and IKKbeta proteins. CONCLUSION: RC-derived diterpenoid C can block
      NF-kappaB signal pathway, effectively reducing the secretion of H. pylori-induced
      proinflammatory cytokine and increasing the secretion of anti-inflammatory
      cytokine.

PMID- 23964143
TI  - Acute effects of rotavirus and malnutrition on intestinal barrier function in
      neonatal piglets.
AB  - AIM: To investigate the effect of protein-energy malnutrition on intestinal
      barrier function during rotavirus enteritis in a piglet model. METHODS: Newborn
      piglets were allotted at day 4 of age to the following treatments: (1) full
      strength formula (FSF)/noninfected; (2) FSF/rotavirus infected; (3) half-strength
      formula (HSF)/noninfected; or (4) HSF/rotavirus infected. After one day of
      adjustment to the feeding rates, pigs were infected with rotavirus and acute
      effects on growth and diarrhea were monitored for 3 d and jejunal samples were
      collected for Ussing-chamber analyses. RESULTS: Piglets that were malnourished or
      infected had lower body weights on days 2 and 3 post-infection (P < 0.05). Three
      days post-infection, marked diarrhea and weight loss were accompanied by sharp
      reductions in villus height (59%) and lactase activity (91%) and increased crypt
      depth (21%) in infected compared with non-infected pigs (P < 0.05). Malnutrition
      also increased crypt depth (21%) compared to full-fed piglets. Villus:crypt ratio
      was reduced (67%) with viral infection. There was a trend for reduction in
      transepithelial electrical resistance with rotavirus infection and malnutrition
      (P = 0.1). (3)H-mannitol flux was significantly increased (50%; P < 0.001) in
      rotavirus-infected piglets compared to non-infected piglets, but there was no
      effect of nutritional status. Furthermore, rotavirus infection reduced
      localization of the tight junction protein, occludin, in the cell membrane and
      increased localization in the cytosol. CONCLUSION: Overall, malnutrition had no
      additive effects to rotavirus infection on intestinal barrier function at day 3
      post-infection in a neonatal piglet model.

PMID- 23964144
TI  - Colonic preparation before colonoscopy in constipated and non-constipated
      patients: a randomized study.
AB  - AIM: To compare the efficacy of different doses of sodium phosphate (NaP) and
      polyethylenglicol (PEG) alone or with bisacodyl for colonic cleansing in
      constipated and non-constipated patients. METHODS: Three hundred and forty-nine
      patients, older than 18 years old, with low risk for renal damage and who were
      scheduled for outpatient colonoscopy were randomized to receive one of the
      following preparations (prep): 90 mL of NaP (prep 1); 45 mL of NaP + 20 mg of
      bisacodyl (prep 2); 4 L of PEG (prep 3) or 2 L of PEG + 20 mg of bisacodyl (prep
      4). Randomization was stratified by constipation. Patients, endoscopists,
      endoscopists' assistants and data analysts were blinded. A blinding challenge was
      performed to endoscopist in order to reassure blinding. The primary outcome was
      the efficacy of colonic cleansing using a previous reported scale. Secondary
      outcomes were tolerability, compliance, side effects, endoscopist perception
      about the necessity to repeat the study due to an inadequate colonic preparation
      and patient overall perceptions. RESULTS: Information about the primary outcome
      was obtained from 324 patients (93%). There were no significant differences
      regarding the preparation quality among different groups in the overall analysis.
      Compliance was higher in the NaP preparations being even higher in half-dose with
      bisacodyl: 94% (prep 1), 100% (prep 2), 81% (prep 3) and 87% (prep 4) (2 vs 1, 3
      and 4, P < 0.01; 1 vs 3, 4, P < 0.05). The combination of bisacodyl with NaP was
      associated with insomnia (P = 0.04). In non-constipated patients the preparation
      quality was also similar between different groups, but endoscopist appraisal
      about the need to repeat the study was more frequent in the half-dose PEG plus
      bisacodyl than in whole dose NaP preparation: 11% (prep 4) vs 2% (prep 1) (P <
      0.05). Compliance in this group was also higher with the NaP preparations: 95%
      (prep 1), 100% (prep 2) vs 80% (prep 3) (P < 0.05). Bisacodyl was associated with
      abdominal pain: 13% (prep 1), 31% (prep 2), 21% (prep 3) and 29% (prep 4), (2, 4
      vs 1, 2, P < 0.05). In constipated patients the combination of NaP plus bisacodyl
      presented higher rates of satisfactory colonic cleansing than whole those PEG:
      95% (prep 2) vs 66% (prep 3) (P = 0.03). Preparations containing bisacodyl were
      not associated with adverse effects in constipated patients. CONCLUSION: In non
      constipated patients, compliance is higher with NaP preparations, and bisacodyl
      is related to adverse effects. In constipated patients NaP plus bisacodyl is the
      most effective preparation.

PMID- 23964145
TI  - Diagnostic accuracy of a new point-of-care screening assay for celiac disease.
AB  - AIM: To determine the diagnostic accuracy of a new point-of-care assay detecting
      anti-deamidated gliadin peptides in celiac disease (CD) patients. METHODS: One
      hundred-and-twelve patients (age range: 1.8-79.2 years old) with clinical
      symptoms suggestive of CD and/or first-degree relatives (FDR) of CD patients (n =
      66), and confirmed CD on a gluten-free diet (GFD) (n = 46), were prospectively
      enrolled in the study at Gastroenterology outpatient clinics for adult patients
      and from the Gastroenterology Consultation Ward at the Pediatric Department of
      the University Hospital of Geneva. Written informed consent was obtained from all
      subjects enrolled. The study received approval from the local ethics committee.
      The original CD diagnosis had been based on serum-positive IgA anti-tissue
      transglutaminase enzyme-linked immunosorbent assay (ELISA) (QuantaLiteTM, Inova
      Diagnostics, San Diego, CA, United States) and on biopsy results. Serum samples
      from all study participants were tested by the new CD lateral flow
      immunochromatographic assay (CD-LFIA) device, Simtomax(r) Blood Drop (Augurix SA,
      BioArk, Monthey, Switzerland) to detect immunoglobulin (Ig)A and IgG antibodies
      against deamidated gliadin peptides. The diagnostic performance was evaluated
      using receiver operating characteristic curves with 95%CIs. A cut-off of 2 on the
      Rann colorimetric scale was used to calculate the device's sensitivity and
      specificity. RESULTS: CD-LFIA was highly accurate in detecting untreated celiac
      patients. In the group of patients with CD symptoms and/or FDR, eight new cases
      of CD were detected by ELISA and biopsy. All of these new cases were also
      correctly identified by CD-LFIA. The test yielded four false positive and four
      false negative results. The false positive results were all within the groups
      with clinical symptoms suggestive of CD and/or FDR, whereas the false negative
      results were all within the GFD group. The test yeld a sensitivity of 78.9%
      (95%CI: 54.4-93.9) and specificity of 95.7% (95%CI: 89.4-98.8), and the area
      under the curve reached 0.893 (95%CI: 0.798-0.988). The Kappa coefficient,
      calculated according to the values obtained by two readers from the same device,
      was of 0.96 (SE: 0.06). When the GFD patients were excluded from the analysis,
      the area under the curve reached 0.989 (95%CI: 0.971-1.000) and the Kappa
      coefficient, calculated according to the values obtained by two readers from the
      same device, became 0.96 (SE: 0.07). Furthermore, using the Rann scale cut-off of
      2 without the GFD patients, sensitivity was 100% and specificity was 93.1%
      (95%CI: 83.3-98.1). CONCLUSION: The new CD-LFIA rapid screening test shows good
      diagnostic accuracy, sensitivity and specificity, and may rule out CD in patients
      with CD-related symptoms.

PMID- 23964146
TI  - Rikkunshito improves globus sensation in patients with proton-pump inhibitor
      refractory laryngopharyngeal reflux.
AB  - AIM: To investigate the effect of rikkunshito on laryngopharyngeal reflux (LPR)
      symptoms and gastric emptying in patients with proton-pump inhibitor (PPI)
      refractory LPR. METHODS: In total, 22 patients with LPR were enrolled. Following
      a 2-wk treatment with PPI monotherapy, PPI-refractory LPR patients were randomly
      divided into two treatment groups (rikkunshito alone or rikkunshito plus the PPI,
      lansoprazole). LPR symptoms were assessed using a visual analog scale (VAS)
      score, gastrointestinal symptoms were assessed using the gastrointestinal symptom
      rating scale (GSRS), and gastric emptying was assessed using the radio-opaque
      marker method prior to and 4 wk following treatments. RESULTS: The 4-wk treatment
      with rikkunshito alone and with rikkunshito plus the PPI significantly decreased
      the globus sensation VAS scores. The VAS score for sore throat was significantly
      decreased following treatment with rikkunshito plus PPI but not by rikkunshito
      alone. Neither treatment significantly changed the GSRS scores. Rikkunshito
      improved delayed gastric emptying. We found a significant positive correlation
      between improvements in globus sensation and in gastric emptying (r2 = 0.4582, P
      < 0.05). CONCLUSION: Rikkunshito improved globus sensation in patients with PPI
      refractory LPR, in part, because of stimulation of gastric emptying. Thus,
      rikkunshito is an effective treatment for PPI-refractory LPR.

PMID- 23964147
TI  - Emergency balloon-occluded retrograde transvenous obliteration of ruptured
      gastric varices.
AB  - AIM: To evaluate the effectiveness and safety of emergency balloon-occluded
      retrograde transvenous obliteration (BRTO) for ruptured gastric varices. METHODS:
      Emergency BRTO was performed in 17 patients with gastric varices and gastrorenal
      or gastrocaval shunts within 24 h of hematemesis and/or tarry stool. The gastric
      varices were confirmed by endoscopy, and the gastrorenal or gastrocaval shunts
      were identified by contrast-enhanced computed tomography (CE-CT). A 6-Fr balloon
      catheter (Cobra type) was inserted into the gastrorenal shunt via the right
      internal jugular vein, or into the gastrocaval shunt via the right femoral vein,
      depending on the varices drainage route. The sclerosant, 5% ethanolamine oleate
      iopamidol, was injected into the gastric varices through the catheter during
      balloon occlusion. In patients with incomplete thrombosis of the varices after
      the first BRTO, a second BRTO was performed the following day. Patients were
      followed up by endoscopy and CE-CT at 1 d, 1 wk, and 1, 3 and 6 mo after the
      procedure, and every 6 mo thereafter. RESULTS: Complete thrombosis of the gastric
      varices was not achieved with the first BRTO in 7/17 patients because of large
      gastric varices. These patients underwent a second BRTO on the next day, and
      additional sclerosant was injected through the catheter. Complete thrombosis
      which led to disappearance of the varices was achieved in 16/17 patients, while
      the remaining patient had incomplete thrombosis of the varices. None of the
      patients experienced rebleeding or recurrence of the gastric varices after a
      median follow-up of 1130 d (range 8-2739 d). No major complications occurred
      after the procedure. However, esophageal varices worsened in 5/17 patients after
      a mean follow-up of 8.6 mo. CONCLUSION: Emergency BRTO is an effective and safe
      treatment for ruptured gastric varices.

PMID- 23964149
TI  - Preclinical evaluation of herpes simplex virus armed with granulocyte-macrophage
      colony-stimulating factor in pancreatic carcinoma.
AB  - AIM: To investigate the therapeutic efficacy and mechanisms of action of
      oncolytic-herpes-simplex-virus encoding granulocyte-macrophage colony-stimulating
      factor (HSV(GM-CSF)) in pancreatic carcinoma. METHODS: Tumor blocks were
      homogenized in a sterile grinder in saline. The homogenate was injected into the
      right armpit of each mouse. After vaccination, the mice were randomly assigned
      into four groups: a control group, a high dose HSV(GM-CSF) group [1 * 107 plaque
      forming units (pfu)/tumor], a medium dose HSV(GM-CSF) group (5 * 106 pfu/tumor)
      and a low dose HSV(GM-CSF) group (5 * 105 pfu/tumor). After initiation of drug
      administration, body weights and tumor diameters were measured every 3 d. Fifteen
      days later, after decapitation of the animal by cervical dislocation, each tumor
      was isolated, weighed and stored in 10% formaldehyde solution. The drug
      effectiveness was evaluated according to the weight, volume and relative volume
      change of each tumor. Furthermore, GM-CSF protein levels in serum were assayed by
      enzyme-linked immunosorbent assays at 1, 2, 3 and 4 d after injection of HSV(GM
      CSF). RESULTS: Injection of the recombinant mouse HSV encoding GM-CSF resulted in
      a significant reduction in tumor growth compared to the control group, and dose
      dependent effects were observed: the relative tumor proliferation rates of the
      low dose, medium dose and high dose groups on 15 d after injection were 45.5%,
      55.2% and 65.5%, respectively. The inhibition rates of the tumor weights of the
      low, middle, and high dose groups were 41.4%, 46.7% and 50.5%, respectively.
      Furthermore, the production of GM-CSF was significantly increased in the mice
      infected with HSV(GM-CSF). The increase in the GM-CSF level was more pronounced
      in the high dose group compared to the other two dose groups. CONCLUSION: Our
      study provides the first evidence that HSV(GM-CSF) could inhibit the growth of
      pancreatic cancer. The enhanced GM-CSF expression might be responsible for the
      phenomenon.

PMID- 23964148
TI  - Connective tissue diseases in primary biliary cirrhosis: a population-based
      cohort study.
AB  - AIM: To establish the frequency and clinical features of connective tissue
      diseases (CTDs) in a cohort of Chinese patients with primary biliary cirrhosis
      (PBC). METHODS: Three-hundred and twenty-two Chinese PBC patients were screened
      for the presence of CTD, and the systemic involvement was assessed. The
      differences in clinical features and laboratory findings between PBC patients
      with and without CTD were documented. The diversity of incidence of CTDs in PBC
      of different countries and areas was discussed. For the comparison of normally
      distributed data, Student's t test was used, while non-parametric test (Wilcoxon
      test) for the non-normally distributed data and 2 * 2 chi(2) or Fisher's exact
      tests for the ratio. RESULTS: One-hundred and fifty (46.6%) PBC patients had one
      or more CTDs. The most common CTD was Sjogren's syndrome (SS, 121 cases, 36.2%).
      There were nine cases of systemic sclerosis (SSc, 2.8%), 12 of systemic lupus
      erythematosus (SLE, 3.7%), nine of rheumatoid arthritis (RA, 2.8%), and 10 of
      polymyositis (PM, 3.1%) in this cohort. Compared to patients with PBC only, the
      PBC + SS patients were more likely to have fever and elevated erythrocyte
      sedimentation rate (ESR), higher serum immunoglobulin G (IgG) levels and more
      frequent rheumatoid factor (RF) and interstitial lung disease (ILD) incidences;
      PBC + SSc patients had higher frequency of ILD; PBC + SLE patients had lower
      white blood cell (WBC) count, hemoglobin (Hb), platelet count, gamma-glutamyl
      transpeptidase and immunoglobulin M levels, but higher frequency of renal
      involvement; PBC + RA patients had lower Hb, higher serum IgG, alkaline
      phosphatase, faster ESR and a higher ratio of RF positivity; PBC + PM patients
      had higher WBC count and a tendency towards myocardial involvement. CONCLUSION:
      Besides the common liver manifestation of PBC, systemic involvement and overlaps
      with other CTDs are not infrequent in Chinese patients. When overlapping with
      other CTDs, PBC patients manifested some special clinical and laboratory features
      which may have effect on the prognosis.

PMID- 23964150
TI  - HMGB1 gene polymorphisms in patients with chronic hepatitis B virus infection.
AB  - AIM: To characterize high mobility group box chromosomal protein 1 (HMGB1)
      polymorphisms in patients infected with hepatitis B virus (HBV) and determine the
      different patterns in patient subgroups. METHODS: A total of 1495 unrelated Han
      Chinese HBV carriers were recruited in this hospital-based case-control study.
      The HMGB1 1176 G/C polymorphism was genotyped by polymerase chain reaction
      restriction fragment length polymorphism assay. RESULTS: A significant
      association was observed between HMGB1 1176 G/C polymorphism and outcome of HBV
      infection. The subjects bearing 1176G/G genotype had an increased risk of
      susceptibility to chronic hepatitis B, liver cirrhosis and severe hepatitis B
      when compared with those bearing at least one 1176C allele. CONCLUSION: Patients
      with 1176G/G genotype of HMGB1 gene are more likely to have a progressive status
      in HBV infection.

PMID- 23964151
TI  - Radical lymph node dissection and assessment: Impact on gallbladder cancer
      prognosis.
AB  - AIM: To investigate the lymph node metastasis patterns of gallbladder cancer
      (GBC) and evaluate the optimal categorization of nodal status as a critical
      prognostic factor. METHODS: From May 1995 to December 2010, a total of 78
      consecutive patients with GBC underwent a radical resection at Liaocheng People's
      Hospital. A radical resection was defined as removing both the primary tumor and
      the regional lymph nodes of the gallbladder. Demographic, operative and
      pathologic data were recorded. The lymph nodes retrieved were examined
      histologically for metastases routinely from each node. The positive lymph node
      count (PLNC) as well as the total lymph node count (TLNC) was recorded for each
      patient. Then the metastatic to examined lymph nodes ratio (LNR) was calculated.
      Disease-specific survival (DSS) and predictors of outcome were analyzed. RESULTS:
      With a median follow-up time of 26.50 mo (range, 2-132 mo), median DSS was 29.00
      +/- 3.92 mo (5-year survival rate, 20.51%). Nodal disease was found in 37
      patients (47.44%). DSS of node-negative patients was significantly better than
      that of node-positive patients (median DSS, 40 mo vs 17 mo, chi2 = 14.814, P <
      0.001), while there was no significant difference between N1 patients and N2
      patients (median DSS, 18 mo vs 13 mo, chi2 = 0.741, P = 0.389). Optimal TLNC was
      determined to be four. When node-negative patients were divided according to
      TLNC, there was no difference in DSS between TLNC < 4 subgroup and TLNC >= 4
      subgroup (median DSS, 37 mo vs 54 mo, chi2 = 0.715, P = 0.398). For node-positive
      patients, DSS of TLNC < 4 subgroup was worse than that of TLNC >= 4 subgroup
      (median DSS, 13 mo vs 21 mo, chi2 = 11.035, P < 0.001). Moreover, for node
      positive patients, a new cut-off value of six nodes was identified for the number
      of TLNC that clearly stratified them into 2 separate survival groups (< 6 or >=
      6, respectively; median DSS, 15 mo vs 33 mo, chi2 = 11.820, P < 0.001). DSS
      progressively worsened with increasing PLNC and LNR, but no definite cut-off
      value could be identified. Multivariate analysis revealed histological grade,
      tumor node metastasis staging, TNLC and LNR to be independent predictors of DSS.
      Neither location of positive lymph nodes nor PNLC were identified as an
      independent variable by multivariate analysis. CONCLUSION: Both TLNC and LNR are
      strong predictors of outcome after curative resection for GBC. The retrieval and
      examination of at least 6 nodes can influence staging quality and DSS, especially
      in node-positive patients.

PMID- 23964152
TI  - Effects of SAHA on proliferation and apoptosis of hepatocellular carcinoma cells
      and hepatitis B virus replication.
AB  - AIM: To investigate the effects of suberoylanilide hydroxamic acid (SAHA) on
      proliferation and apoptosis of a human hepatocellular carcinoma cell line
      (HepG2.2.15) and hepatitis B virus (HBV) replication. METHODS: HepG2.2.15 cells
      were treated with different concentrations of SAHA. Cell morphology was examined
      by confocal laser scanning microscopy, and cell proliferation was determined
      using a MTT colorimetric assay. Flow cytometry was used to detect apoptosis and
      determine cell cycle phase, while hepatitis B surface antigen and hepatitis B e
      antigen content were measured using chemiluminescence. Reverse transcription
      polymerase chain reaction was performed to measure HBV DNA in cell lysate.
      RESULTS: Cell proliferation rates were significantly reduced by the addition of
      SAHA. The inhibitory effect of SAHA on cell proliferation was both time- and dose
      dependent. After 24 h of treatment with SAHA, the early cell apoptotic rate
      increased from 3.25% to 21.02% (P = 0.041). The proportion of G0/G1 phase cells
      increased from 50.3% to 65.3% (P = 0.039), while that of S phase cells decreased
      from 34.9% to 20.6% (P = 0.049). After 48 h of treatment, hepatitis B surface
      antigen and hepatitis B e antigen content increased from 12.33 +/- 0.62 to 25.42
      +/- 2.67 (P = 0.020) and 28.92 +/- 1.24 to 50.48 +/- 1.85 (P = 0.026),
      respectively. Furthermore, HBV DNA content increased from 4.54 +/- 0.46 to 8.34
      +/- 0.59 (P = 0.029). CONCLUSION: SAHA inhibits HepG2.2.15 cell proliferation,
      promotes apoptosis, and stimulates HBV replication. In combination with anti-HBV
      drugs, SAHA may potentially be used cautiously for treatment of hepatocellular
      carcinoma.

PMID- 23964154
TI  - Green tea extract: a potential cause of acute liver failure.
AB  - The use of herbal products has increased significantly in recent years. Because
      these products are not subject to regulation by the Food and Drug Administration
      and are often used without supervision by a healthcare provider, the indication
      for and consumption of these supplements is quite variable. Moreover, their use
      is generally regarded as safe and natural by the lay-public. Unfortunately, there
      has been an increase in the number of reported adverse events occurring with the
      use of herbal products. We present a case of acute impending liver failure in an
      adolescent male using a weight-loss product containing green tea extract. Our
      case adds to the growing concern surrounding the ingestion of green tea extract
      and serves to heighten healthcare provider awareness of a potential green tea
      extract hepatotoxicity. Despite the generally touted benefits of green tea as a
      whole, clinical concern regarding its use is emerging and has been linked to its
      concentration in multiple herbal supplements. Interestingly, the suspected
      harmful compounds are those previously proposed to be advantageous for weight
      loss, cancer remedy, and anti-inflammatory purposes. Yet, we emphasize the need
      to be aware of not just green tea extract, but the importance of monitoring
      patient use of all dietary supplements and herbal products. 

PMID- 23964153
TI  - Single-incision laparoscopic appendectomy vs conventional laparoscopic
      appendectomy: systematic review and meta-analysis.
AB  - AIM: To assess the differences in clinical benefits and disadvantages of single
      incision laparoscopic appendectomy (SILA) and conventional laparoscopic
      appendectomy (CLA). METHODS: The Cochrane Library, MEDLINE, Embase, Science
      Citation Index Expanded, and Chinese Biomedical Literature Database were
      electronically searched up through January 2013 to identify randomized controlled
      trails (RCTs) comparing SILA with CLA. Data was extracted from eligible studies
      to evaluate the pooled outcome effects for the total of 1068 patients. The meta
      analysis was performed using Review Manager 5.2.0. For dichotomous data and
      continuous data, the risk ratio (RR) and the mean difference (MD) were
      calculated, respectively, with 95%CI for both. For continuous outcomes with
      different measurement scales in different RCTs, the standardized mean difference
      (SMD) was calculated with 95%CI. Sensitivity and subgroup analyses were performed
      when necessary. RESULTS: Six RCTs were identified that compared SILA (n = 535)
      with CLA (n = 533). Five RCTs had a high risk of bias and one RCT had a low risk
      of bias. SILA was associated with longer operative time (MD = 5.68, 95%CI: 3.91
      7.46, P < 0.00001), higher conversion rate (RR = 5.14, 95%CI: 1.25-21.10, P =
      0.03) and better cosmetic satisfaction score (MD = 0.52, 95%CI: 0.30-0.73, P <
      0.00001) compared with CLA. No significant differences were found for total
      complications (RR = 1.15, 95%CI: 0.76-1.75, P = 0.51), drain insertion (RR =
      0.72, 95%CI: 0.41-1.25, P = 0.24), or length of hospital stay (SMD = 0.04, 95%CI:
      -0.08-0.16, P = 0.57). Because there was not enough data among the analyzed RCTs,
      postoperative pain was not calculated. CONCLUSION: The benefit of SILA is
      cosmetic satisfaction, while the disadvantages of SILA are longer operative time
      and higher conversion rate.

PMID- 23964155
TI  - Total dysphagia after short course of systemic corticotherapy: herpes simplex
      virus esophagitis.
AB  - A 72 year-old female developed a herpetic esophagitis after 3 d of oral
      corticotherapy for an acute exacerbation of chronic obstructive pulmonary
      disease, presenting as odynophagia and total dysphagia. Biopsies were taken
      during a first esophagogastroduodenoscopy (EGD) and the patient was referred to
      the thoracic surgery service with a presumptive diagnosis of esophageal cancer. A
      second EGD was planned for dilatation, but by that time the stenosis was
      completely resolved. The biopsies taken during the first EGD revealed multiple
      herpetic viral inclusions and ulcerations without any dysplasia or neoplasia. In
      front of a severe esophageal stenosis, one must still exclude the usual
      differential diagnosis peptic stenosis and cancer. Visualization of endoscopic
      lesions can suggest the diagnosis but must be promptly confirmed by biopsy, viral
      culture or polymerase chain reaction. Although immune systemic effects of
      corticotherapy are well known and herpetic esophagitis occurs most frequently in
      immunocompromised individuals, this case emphasizes the importance of clinical
      awareness concerning short courses of corticotherapy for immunocompetent
      individuals. This article discusses the reactivation process of herpetic
      infection in this context and addresses its diagnostic and therapeutic issues.

PMID- 23964156
TI  - Pancreatic duct drainage using EUS-guided rendezvous technique for stenotic
      pancreaticojejunostomy.
AB  - The patient was a 30-year-old female who had undergone excision of the
      extrahepatic bile duct and Roux-en-Y hepaticojejunostomy for congenital biliary
      dilatation at the age of 7. Thereafter, she suffered from recurrent acute
      pancreatitis due to pancreaticobiliary maljunction and received subtotal stomach
      preserving pancreaticoduodenectomy. She developed a pancreatic fistula and an
      intra-abdominal abscess after the operation. These complications were improved by
      percutaneous abscess drainage and antibiotic therapy. However, upper abdominal
      discomfort and the elevation of serum pancreatic enzymes persisted due to
      stenosis from the pancreaticojejunostomy. Because we could not accomplish
      dilation of the stenosis by endoscopic retrograde cholangiopancreatography, we
      tried an endoscopic ultrasonography (EUS) guided rendezvous technique for
      pancreatic duct drainage. After transgastric puncture of the pancreatic duct
      using an EUS-fine needle aspiration needle, the guidewire was inserted into the
      pancreatic duct and finally reached to the jejunum through the stenotic
      anastomosis. We changed the echoendoscope to an oblique-viewing endoscope, then
      grasped the guidewire and withdrew it through the scope. The stenosis of the
      pancreaticojejunostomy was dilated up to 4 mm, and a pancreatic stent was put in
      place. Though the pancreatic stent was removed after three months, the patient
      remained symptom-free. Pancreatic duct drainage using an EUS-guided rendezvous
      technique was useful for the treatment of a stenotic pancreaticojejunostomy after
      pancreaticoduodenectomy. 

PMID- 23964157
TI  - Complete response to multidisciplinary therapy in a patient with primary gastric
      choriocarcinoma.
AB  - Primary gastric choriocarcinoma is a rapidly growing neoplasm with an average
      survival of several months in untreated patients. Gastrectomy with lymph node
      dissection followed by chemotherapy is the treatment of choice. Regimens used for
      gastric adenocarcinoma are usually selected. However, median survival remains
      less than six months. In this case report, we describe a case of primary gastric
      choriocarcinoma with a clinical complete response to multidisciplinary treatment
      including surgery, chemotherapy, and radiofrequency ablation (RFA). The patient
      was originally referred for general malaise. Esophagogastroduodenoscopy
      demonstrated a large tumor occupying the fornix, and total gastrectomy with lymph
      node dissection was performed. Seven days later, multiple liver metastatic
      recurrences with high serum levels of beta-human chorionic gonadotropin (beta
      hCG) were recognized. Chemotherapy with a gonadal choriocarcinoma regimen
      consisting of etoposide, methotrexate, actinomycin D, cyclophosphamide, and
      vincristine (EMA/CO), was initiated. After three cycles, serum beta-hCG decreased
      markedly and the tumors disappeared. Six months later, multiple lung metastatic
      recurrences were found. After one cycle of EMA/CO, only one nodule remained.
      Computed tomography-guided RFA was performed for this oligometastatic tumor. The
      patient has been alive with no evidence of disease for 10 years after the initial
      diagnosis. To the best of our knowledge, this patient with recurrent primary
      gastric choriocarcinoma has achieved the longest survival. The present case is
      the first report of choriocarcinoma metastatic to the lung successfully treated
      with RFA. From our retrospective analysis of recurrent or unresectable primary
      gastric choriocarcinoma, we propose that gonadal choriocarcinoma regimens can be
      considered as first-line for primary gastric choriocarcinoma. 

PMID- 23964158
TI  - Radical excision of Barrett's esophagus and complete recovery of normal squamous
      epithelium.
AB  - To treat Barrett's esophagus (BE), radiofrequency ablation or cryotherapy are
      effective treatments for eradicating BE with dysplasia and intestinal metaplasia,
      and reduce the rates of Barrett's esophageal adenocarcinoma (BAC). However,
      patients with BE and dysplasia or early cancer who achieved complete eradication
      of intestinal metaplasia, BE recurred in 5% within a year, requiring expensive
      endoscopic surveillances. We performed endoscopic submucosal dissection as
      complete radically curable treatment procedure for BE with dysplasia, intestinal
      metaplasia and BAC. 

PMID- 23964159
TI  - Isolated splenic metastases from gastric carcinoma: a case report and literature
      review.
AB  - Isolated metastases to the spleen from gastric carcinoma is very rare. Only a few
      cases have been reported in the literature. We herein present a case of isolated
      splenic metastases in a 62-year-old man, occurring 12 mo after total gastrectomy
      for gastric carcinoma. The patient underwent a laparoscopic exploration, during
      which two lesions were found at the upper pole of the spleen, without involvement
      of other organs. A laparoscopic splenectomy was performed. Histological
      examination confirmed that the splenic tumor was a poorly differentiated
      adenocarcinoma similar to the primary gastric lesion. The postoperative course
      was uneventful and the patient has been well for 9 mo, with no tumor recurrence.
      The clinical data of 18 cases of isolated splenic metastases from gastric
      carcinoma treated by splenectomy were summarized after a literature review. To
      our knowledge, this is the first reported case of isolated splenic metastases
      undergoing laparoscopic splenectomy. 

PMID- 23964160
TI  - Chronic pancreatitis as presentation of Crohn's disease in a child.
AB  - It is reported that a pancreatic disease may precede the diagnosis of
      inflammatory bowel disease (IBD) both in children and in adults. Idiopathic
      chronic pancreatitis, however, occasionally co-exists with the IBD, mainly at
      pediatric age. We report a case of a patient who progressively developed the
      features of a chronic pancreatitis, before the diagnosis of Crohn's Disease (CD).
      Ten months after the onset of the first episode of pancreatitis the patient
      developed bloody diarrhea, mucus stools and biochemical findings of inflammation.
      The colonoscopy revealed a diffuse colitis without involvement of the last loop
      and the gastroscopy showed inflammation of the iuxta-papillary area. The
      histological findings confirmed the diagnosis of CD that involved the colon and
      the duodenum. In conclusion, in children the idiopathic chronic pancreatitis may
      be an unusual presentation of CD. Thus, if other known cause of chronic
      pancreatitis are not found, a not invasive work up to exclude the IBD should be
      warranted. An early coincidental diagnosis of the IBD may delay the progression
      of the pancreatic disease. 

PMID- 23964161
TI  - Evolution in pharmacologic thinking around the natural analgesic
      palmitoylethanolamide: from nonspecific resistance to PPAR-alpha agonist and
      effective nutraceutical.
AB  - The history of development of new concepts in pharmacology is a highly
      interesting topic. This review discusses scientific insights related to
      palmitoylethanolamide (PEA) and its progression over a period of six decades,
      especially in light of the work of the science sociologists, Ludwig Fleck and
      Thomas Kuhn. The discovery of the cannabis receptors and the nuclear peroxisome
      proliferator-activated receptors was the beginning of a completely new
      understanding of many important homeostatic physiologic mechanisms in the human
      body. These discoveries were necessary for us to understand the analgesic and
      anti-inflammatory activity of PEA, a body-own fatty amide. PEA is a nutrient
      known already for more than 50 years. PEA is synthesized and metabolized in
      animal cells via a number of enzymes and has a multitude of physiologic functions
      related to metabolic homeostasis. PEA was identified in the 1950s as a
      therapeutic principle with potent anti-inflammatory properties. Since 1975, its
      analgesic properties have been noted and explored in a variety of chronic pain
      states. Since 2008, PEA has been available as a nutraceutical under the brand
      names Normast(r) and PeaPure(r). A literature search on PEA meanwhile has yielded
      over 350 papers, all referenced in PubMed, describing the physiologic properties
      of this endogenous modulator and its pharmacologic and therapeutic profile. This
      review describes the emergence of concepts related to the pharmacologic profile
      of PEA, with an emphasis on the search into its mechanism of action and the
      impact of failing to identify such mechanism in the period 1957-1993, on the
      acceptance of PEA as an anti-inflammatory and analgesic compound. 

PMID- 23964162
TI  - Evaluation of clinical activity and safety of Daflon 500 mg in type 2 diabetic
      female patients.
AB  - BACKGROUND: The incidence of cardiovascular disease in patients with type 2
      diabetes mellitus is approximately twice as high as in the non-diabetic
      population. AIM: To investigate the hypoglycemic and hypocholesterolemic effects
      of Daflon((r)) 500 mg (DF) administration together with its tolerability and
      efficacy in reducing the cardiovascular metabolic risk factors in female patients
      with type 2 diabetes. METHODS: In a well-adequate controlled single-blinded
      randomized parallel design the tolerability and the efficacy of Daflon((r)) (500
      mg) either alone or with oral hypoglycemic, twice daily for 45 days, was studied
      in 36 female patients with type 2 diabetes. RESULTS: None of the patients in the
      studied groups were reported to have any adverse events throughout the treatment
      period (45 days), liver and kidney function tests were within normal limits and
      there was no significant difference between the pre-treatment (day 0) and post
      treatment (day 45) values. Female patients receiving Daflon((r)) either alone or
      with oral hypoglycemic showed significant decrease in serum glucose;
      fructosamine; total cholesterol; LDL-cholesterol; triglycerides; malondialdehydes
      (as index of lipid peroxidation) and C-reactive protein (CRB) levels along with
      increase in the levels of nitric oxide and blood glutathione. CONCLUSION: This
      study has shown that Daflon((r)) (500 mg, twice daily for 45 days) is helpful in
      reducing glucose level and the risk of cardiovascular disease in type 2 diabetic
      patients. RECOMMENDATION: Further clinical trials are essential for strengthening
      the evidence base on the role of this drug in the cardiovascular risk in diabetic
      patients.

PMID- 23964163
TI  - Possible hypoglycemic effect of Aloe vera L. high molecular weight fractions on
      type 2 diabetic patients.
AB  - Aloe vera L. high molecular weight fractions (AHM) containing less than 10 ppm of
      barbaloin and polysaccharide (MW: 1000 kDa) with glycoprotein, verectin (MW: 29
      kDa), were prepared by patented hyper-dry system in combination of freeze-dry
      technique with microwave and far infrared radiation. AHM produced significant
      decrease in blood glucose level sustained for 6 weeks of the start of the study.
      Significant decrease in triglycerides was only observed 4 weeks after treatment
      and continued thereafter. No deterious effects on kidney and liver functions were
      apparent. Treatment of diabetic patients with AHM may relief vascular
      complications probably via activation of immunosystem. 

PMID- 23964164
TI  - Improvement of solubility and dissolution rate of indomethacin by solid
      dispersions in Gelucire 50/13 and PEG4000.
AB  - The aim of this study was to prepare and characterize solid dispersions of water
      insoluble non-steroidal anti-inflammatory drug, indomethacin (IND), with
      polyethylene glycol 4000 (PEG4000) and Gelucire 50/13 (Gelu.) for enhancing the
      dissolution rate of the drug. The solid dispersions (SDs) were prepared by hot
      melting method at 1:1, 1:2 and 1:4 drug to polymer ratios. Scanning electron
      microscopy (SEM), X-ray powder diffractometry (XRD) and differential scanning
      calorimetry (DSC) were used to examine the physical state of the drug.
      Furthermore, the solubility and the dissolution rate of the drug in its different
      systems were explored. The data from the XRD showed that the drug was still
      detectable in its solid state in all SDs of IND-Gelu. and disappeared in case of
      higher ratio of IND-PEG4000. DSC thermograms showed the significant change in
      melting peak of the IND when prepared as SDs suggesting the change in
      crystallinity of IND. The highest ratio of the polymer (1:4) enhanced the drug
      solubility about 4-folds or 3.5-folds in case of SDs of IND-PEG or IND-Gelu.,
      respectively. An increased dissolution rate of IND at pH 1.2 and 7.4 was observed
      when the drug was dispersed in these carriers in form of physical mixtures (PMs)
      or SDs. IND released faster from the SDs than from the pure crystalline drug or
      the PMs. The dissolution rate of IND from its PMs or SDs increased with an
      increasing amount of polymer. 

PMID- 23964165
TI  - Inhibition of growth of Leishmania donovani promastigotes by newly synthesized
      1,3,4-thiadiazole analogs.
AB  - Leishmania donovani, the causative agent of visceral leishmaniasis, is
      transmitted by sand flies and replicates intracellularly in their mammalian host
      cells. The emergence of drug-resistant strains has hampered efforts to control
      the spread of the disease worldwide. Forty-four 1,3,4-thiadiazole derivatives and
      related compounds were tested in vitro for possible anti-leishmanial activity
      against the promastigotes of L. donovani. Micromolar concentrations of these
      agents were used to study the inhibition of multiplication of L. donovani
      promastigotes. Seven compounds were identified with potential antigrowth agents
      of the parasite. Compound 4a was the most active at 50 MUM followed by compound
      3a. These compounds could prove useful as a future alternative for the control of
      visceral leishmaniasis. 

PMID- 23964166
TI  - Effects of plasticizers and surfactants on the film forming properties of
      hydroxypropyl methylcellulose for the coating of diclofenac sodium tablets.
AB  - Hydroxy propyl methyl cellulose (HPMC) 5cPs, an aqueous soluble polymer was
      employed for coating diclofenac sodium (DFS) tablets 25 mg for protecting the
      integrity of the drug yet rendering the drug to release at a faster rate on
      contact with the gastric environment. Proper optimization for the aqueous based
      film coating formulation was undertaken primarily employing plasticizers like
      polyethylene glycol (PEG) 400 and propylene glycol (PG). The defect free selected
      formulations were further subjected for studying the effects of surfactants like
      sodium lauryl sulphate (SLS) and Tween-80 along with the plasticizers. The
      quality of the aqueous film coats or the plasticizer efficiency in case of PEG
      400 is in the order 1.5 > 0.5 > 1.0% and for PG 1 > 4 > 3% which can be stated on
      the basis of less incidence of major coat defects like chipping, cracking, orange
      peel, roughness, blistering, blooming, picking. The quality of aqueous film coat
      or the surfactant efficiency in case of SLS + PEG-400 is in the order 0.3 < 0.5 <
      0.1% and SLS + PG is in the order 0.5 < 0.1 < 0.3%. In case of Tween-80 + PEG-400
      the order is 0.3 < 0.5 < 0.1% and Tween-80 + PG is in the order 0.3 < 0.1 < 0.5%.
      Elegant film formation can be stated from fewer incidences of coat defects. The
      obtained coated tablets eventually satisfied all the normal physical parameters
      like thickness, weights, and weight gain, drug content, crushing strength,
      percent friability, disintegration time, dissolution profile and possible drug
      polymer interactions. ANOVA was undertaken followed by Dunnet multiple comparison
      for the dissolution profile considering uncoated as the standard. The difference
      was considered significant at p ? 0.01. 

PMID- 23964167
TI  - Safety and efficacy of terbinafine in a pediatric Iranian cohort of patients with
      Tinea capitis.
AB  - BACKGROUND AND OBJECTIVES: Tinea capitis is a common infection of the scalp and
      hair shaft caused by dermatophyte fungi that mainly affects prepubescent
      children. Systemic therapy is required for treatment and to prevent spread. The
      aim of present study was to assess the effect of terbinafine for Tinea capitis
      treatment in children. METHODS: Thirty Iranian pediatric patients with a clinical
      diagnosis of Tinea capitis were enrolled in the study. The Study was conducted in
      a general and referral teaching hospital (Imam Medical Centre - Tehran, Iran)
      from 2006 to 2007. Eligible patients with less than 20 kg of body weight were
      given 62.5 mg terbinafine, and for patients between 20 and 40 kg the dose was 125
      mg, on the first visit. All patients had the second clinical visit and second
      samples for microscopic study were taken. For each patient, direct mycology test
      (KOH test) and mycological culture were carried out before the study was started
      and after second, fourth, fifth, sixth and eighth weeks. Probable drug's adverse
      effects were also recorded. RESULTS: Based on the results of mycological culture
      of patients' lesions, Microsporum canis and Trichophyton sheonlini were
      considered as major causes of Tinea capitis in these children. Out of 30 study
      patients, KOH test of 93% in the 5th week and 100% in the 6th week was negative.
      All patients healed completely from signs of infection, after six weeks. Also, no
      severe side effects were seen in any patients. CONCLUSION: According to the
      results of this study, the use of terbinafine is an effective therapy in Iranian
      cases of Tinea capitis in children without severe side effects.

PMID- 23964168
TI  - Determination of the binding sites of propranolol HCl on bovine serum albumin by
      direct and reverse procedures.
AB  - To characterize the binding site of propranolol hydrochloride, the free
      concentration of warfarin (site-I-specific probe) bound to BSA was measured upon
      the addition of propranolol hydrochloride. It was found that the free
      concentration of warfarin sodium was increased from 100% (as % of initial) to
      552.35% when the ratio of propranolol to BSA was increased 1-6. In contrast,
      under the same experimental conditions, when diazepam was used as a site-II
      specific probe, the increment of the free concentration of diazepam by
      propranolol was from 100% (as % of initial) to 415.42. From these data it is
      evident that the increment of free concentration of warfarin sodium is obviously
      greater than that of diazepam by propranolol. So it can be concluded that
      propranolol preferentially binds to site-I. Again as the displacement of diazepam
      is quite enough it can also be suggested that propranolol in addition to site-I
      also binds to site-II on the BSA molecule but to a lower extent. Again in the
      reverse experiment, the free concentration of propranolol was increased from 100%
      (as % of initial) to 476% when warfarin to BSA ratio was 1-6 as shown, on the
      other hand, the free concentration of propranolol was increased from 100% (as %
      initial) to 222.39% when the ratio of diazepam to BSA was also 1-6. From the data
      it is clear that the increment of propranolol due to displacement by warfarin
      (site-I probe) is higher than that of propranolol when displaced by diazepam
      (site-II probe). Thus this reverse experiment also agrees with the previous
      experiment. 

PMID- 23964169
TI  - Synthesis and anti-histaminic activity of some novel pyrimidines.
AB  - Novel pyrimidines were prepared by the condensation of chalcones of 4'-piperazine
      acetophenone with guanidine HCl. The structures of the synthesized compounds RP 1
      5 were assigned on the basis of elemental analysis, IR, (1)H NMR and mass
      spectroscopy. These compounds were also screened for anti-histaminic activity.
      The recorded percentage of histamine inhibition showed a significant anti
      histaminic activity when compared to the reference anti-histaminic drug
      mepiramine. 

PMID- 23964170
TI  - Cardioprotective and neuroprotective roles of oleuropein in olive.
AB  - Traditional diets of people living in the Mediterranean basin are, among other
      components, very rich in extra-virgin olive oil, the most typical source of
      visible fat. Olive is a priceless source of monounsaturated and di-unsaturated
      fatty acids, polyphenolic antioxidants and vitamins. Oleuropein is the main
      glycoside in olives and is responsible for the bitter taste of immature and
      unprocessed olives. Chemically, oleuropein is the ester of elenolic acid and 3,4
      dihydroxyphenyl ethanol, which possesses beneficial effects on human health, such
      as antioxidant, antiatherogenic, anti-cancer, anti-inflammatory and antimicrobial
      properties. The phenolic fraction extracted from the leaves of the olive tree,
      which contains significant amounts of oleuropein, prevents lipoprotein oxidation.
      In addition, oleuropein has shown cardioprotective effect against acute
      adriamycin cardiotoxicity and an anti-ischemic and hypolipidemic activities.
      Recently, oleuropein has shown neuroprotection by forming a non-covalent complex
      with the Abeta peptide, which is a key hallmark of several degenerative diseases
      like Alzheimer and Parkinson. Thus, a large mass of research has been
      accumulating in the area of olive oil, in the attempt to provide evidence for the
      health benefits of olive oil consumption and to scientifically support the
      widespread adoption of traditional Mediterranean diet as a model of healthy
      eating. These results provide a molecular basis for some of the benefits
      potentially coming from oleuropein consumption and pave the way to further
      studies on the possible pharmacological use of oleuropein to prevent or to slow
      down the cardiovascular and neurodegenerative diseases. 

PMID- 23964171
TI  - Synthesis, antimicrobial and antiviral testing of some new 1-adamantyl analogues.
AB  - A new series of 1-adamantyl derivatives was designed, synthesized and evaluated
      for their antimicrobial and antiviral activities. Representative derivatives of
      the newly synthesized compounds were tested. Ampicillin, clotimazole and the
      antiviral antibiotic aphidicolin were used as positive controls. Compound 18
      proved to be the most active member of this series as antimicrobial against
      Staphylococcus aureus and Candida albicans and as antiviral with IC50 value of
      0.21 mg/ml and CD50 value of 0.02 mg/ml while compound 19 proved to be the most
      active member of this series as antiviral with IC50 value of 0.21 mg/ml and CD50
      value of 0.01 mg/ml. 

PMID- 23964172
TI  - Synthesis and antimicrobial activity of new 4-thiazolidinone derivatives
      containing 2-amino-6-methoxybenzothiazole.
AB  - A novel series of Schiff bases 5a-j and 4-thiazolidinones 6a-j have been prepared
      from the building blocks 2-chloro pyridine-3-carboxylic acid [1] and 2-amino-6
      methoxy-benzothiazole [2]. All of the synthesized compounds have been confirmed
      by elemental analyses, IR, (1)H NMR and (13)C NMR spectral data. These newly
      synthesized compounds were screened for their antimicrobial activity. Variable
      and modest activity was observed against the investigated strains of bacteria and
      fungi, however, compound 6h revealed significant antibacterial activity against
      Escherichia coli. Compounds 1, 2, 3, 5c, 5g and 5h, on the other hand, revealed
      potent antifungal activity against Candida albicans compared to the reference
      drug greseofulvin. 

PMID- 23964173
TI  - Comparative study between peripherally and centrally acting sublethal and lethal
      doses of Leiurus quinquestriatus scorpion venom in rabbits: The usefulness of the
      sodium channel blocker lidocaine.
AB  - BACKGROUND: Scorpion envenomation is common among desert dwellers, affecting
      several systems and resulting in multiple organ dysfunction (MOD) or failure
      (MOF), mainly due to their action on Na(+) channels. Although scorpion venoms
      toxins do not pass the blood brain barrier, their CNS effects are prominent,
      occurring in conjunction with, or as an aftermath of peripheral actions of the
      venom. OBJECTIVE: To determine the ability of venom of the common scorpion
      Leiurus quinquestriatus (LQQ) to induce MOD or MOF when injected into rabbits in
      micro quantities centrally (intracerebroventricularly, i.c.v.) or macro amounts
      peripherally (s.c. or i.v.). Also, to assess if the Na(+) channel blocker
      lidocaine can protect rabbits from the resultant manifestations. METHODS: Rabbits
      were injected with LQQ venom centrally or peripherally, in either sublethal or
      lethal doses, and MOD or MOF determined by assessing: cardiac output (CO),
      estimated hepatic blood flow (EHBF), biochemical parameters indicative of
      cardiac/hepatic/renal and pancreatic functions, blood pressure (BP), survival,
      lung/body index (LBI, indicative of pulmonary edema), and/or histological changes
      in hearts, lungs, livers plus kidneys. In pre-treatment experiments, lidocaine
      was injected 40 min before venom and protective ability examined. RESULTS: LQQ
      venom in sublethal doses caused comparable significant reductions (vs control) in
      CO and EHBF when injected i.c.v. (2 MUg kg(-1)) or s.c. (0.2 mg kg(-1)). Both
      routes caused gradual dose-related enhanced levels of creatine kinase, lactate
      dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatinine,
      glucose and amylase, indicating MOD. Also, characteristic venom-induced changes
      in BP were evident after lethal doses of venom i.v. (0.5 mg kg(-1)) or i.c.v. (3
      MUg kg(-1)). Histological changes in the organs plus LBI were comparable after
      i.c.v. and i.v. venom injection, with animals ultimately exhibiting MOF.
      Lidocaine (1 mg kg(-1) i.v., then infusion 50 MUg kg(-1) min(-1), 30 min before
      venom), protected the animals from MOF evoked by lethal doses of the venom
      (whether injected centrally or peripherally), as evidenced by the amelioration of
      the venom's effects on blood pressure, LBI, survival and multiple organ
      histopathological manifestations. CONCLUSION: LQQ venom, whether injected
      centrally or peripherally caused comparable systemic dose-dependent MOD or MOF,
      with the latter attenuated by the Na(+) channel blocker lidocaine, indicating a
      role for Na(+) channels.

PMID- 23964174
TI  - HPTLC-densitometric method for simultaneous determination of salmeterol xinafoate
      and fluticasone propionate in dry powder inhalers.
AB  - A high performance thin layer chromatography (HPTLC) method was developed and
      validated for determination of two anti-asthmatic drugs, salmeterol xinafoate and
      fluticasone propionate in co-formulations. Study was performed on pre-coated
      silica gel HPTLC plates using n-hexane:ethyl acetate:acetic acid (5:10:0.2) as a
      mobile phase. A TLC scanner set at 250 nm was used for direct evaluation of the
      chromatograms in reflectance/absorbance mode. Method was validated according to
      ICH guidelines. Determination coefficients of calibration curves were found
      0.9977 and 0.9936 in the ranges 100-1000 and 200-2000 ng band(-1) for salmeterol
      and fluticasone, respectively. Method had an accuracy of 99.5% for salmeterol and
      102.01% for fluticasone. Method had the potential to determine these drugs
      simultaneously from dosage forms without any interference. 

PMID- 23964175
TI  - Immunomodulatory activity of methanolic fruit extract of Aegle marmelos in
      experimental animals.
AB  - AIM: The aim of the present study was to investigate the immunomodulatory action
      of methanolic extract of Aegle marmelos fruit (FEAM) in experimental model of
      immunity. METHODS: Cellular immunity was carried out by neutrophil adhesion test
      and carbon clearance assay, whereas, humoral immunity was analyzed by mice
      lethality test and indirect haemagglutination assay. FEAM dose was selected by
      Stair case method (up and down) and administered at 100 and 500 mg/kg orally. The
      Ocimum sanctum (OSE, 100 mg/kg, p.o) was used as standard. RESULTS: FEAM at 100
      and 500 mg/kg produced significant increases in adhesion of neutrophils and an
      increase in phagocytic index in carbon clearance assay. Both high and low doses
      of FEAM significantly prevented the mortality induced by bovine Pasteurella
      multocida in mice. Treatment of animals with FEAM and OSE significantly increased
      the circulating antibody titre in indirect haemagglunation test. Among the
      different doses, low one was more effective in cellular immunity models than the
      high. However, all the doses exhibited similar protection in humoral immunity
      procedures. CONCLUSION: From the above findings, it is concluded that FEAM
      possesses potential for augmenting immune activity by cellular and humoral
      mediated mechanisms more at low dose (100 mg/kg) than high dose (500 mg/kg).

PMID- 23964176
TI  - Effects of some commonly used Saudi folk herbal medications on the metabolic
      activity of CYP2C9 in human liver microsomes.
AB  - OBJECTIVE: To investigate the potential effects of eleven of the most commonly
      used Saudi folk herbal medications on the metabolic activity of CYP2C9 in human
      liver microsomes. METHOD: CYP2C9-mediated 4'-hydroxylation of tolbutamide (TB) to
      4'-hydroxytolbutamide (4-OH-TB) was utilized to assess the metabolic activity of
      CYP2C9. In the present study, an initial screening of the eleven herbs was
      carried out by incubating TB with microsomes and NADPH in absence or presence of
      a fixed concentration (25 MUg/ml) of alcoholic extracts of different herbs and
      the metabolite formed was measured by HPLC. Herbs that showed significant effects
      were further investigated at a lower range of concentration. RESULTS: Among the
      investigated herbal extracts, only aniseed and curcuma showed statistically
      significant effects on the formation of 4-OH-TB in human liver microsomes.
      Curcuma produced a potent inhibition on the metabolite formation and its maximum
      (about 45% inhibition) was observed at the highest extract concentrations (10 and
      25 MUg/ml). On the other hand, aniseed significantly activates the formation of 4
      OH-TB and the maximum activation (about 55%) was observed at 2.5 MUg/ml of
      aniseed extract. CONCLUSION: The results of this study have shown that alcoholic
      extracts of curcuma and aniseed were capable of inhibiting and activating;
      respectively, the CYP2C9-mediated 4-OH-TB formation in human liver microsomes,
      suggesting that these herbs have the potential to interact with CYP2C9 drug
      substrates. None of the other nine investigated herbs was able to produce any
      statistically significant effect.

PMID- 23964177
TI  - Antihyperglycemic and hypolipidemic effects of Melothria maderaspatana and
      Coccinia indica in Streptozotocin induced diabetes in rats.
AB  - Antihyperglycemic and hypolipidemic effects of ethanol extract of aerial parts of
      Melothria maderaspatana and Coccinia indica were evaluated in STZ induced
      diabetes in Sprague-Dawley rats. The rats were concurrently treated with 100 or
      200 mg/kg b.w. p.o. for 14 days. The changes in fasting blood glucose level and
      body weight were measured in 5 days interval. After 14 days experimental period,
      rats were sacrificed by cervical decapitation, blood and liver samples were
      collected. Biochemical estimation of plasma glucose, cholesterol, triglycerides,
      LDL, HDL, SGOT, SGPT and ALP were done from blood sample. The liver glycogen
      content was estimated using standard procedure from homogenized liver sample.
      Administration of EEMm or EECi to STZ-diabetic rats caused significant
      antihyperglycemic and hypolipidemic effects (p < 0.001). The extracts were also
      found to be significantly effective (p < 0.001; p < 0.05) on recovery of altered
      biochemical parameters and decreased body weight in treated animals.
      Glibenclamide (0.5 mg/kg b.w.) was used as standard in present study. 

PMID- 23964178
TI  - Celebrating the past and planning the future.

PMID- 23964179
TI  - Outcome of an outreach microsurgical project in rural Nepal.
AB  - PURPOSE: This study is aimed at evaluation of the outcome of an outreach program
      conducted in the remote Himalayan part of Nepal. Conclusions will be used to
      improve blindness prevention projects in this country. METHODS: A temporary
      outreach microsurgical clinic was established in Diktel, Nepal. All patients who
      reported to the clinic were examined. Cases requiring surgical treatment, mostly
      cataracts, were operated on. Minor ocular diseases were treated on the spot,
      while the complicated ones were diagnosed, given initial treatment and referred
      to the nearest eye hospital. RESULTS: Examination was performed on 1296 patients;
      84 subjects underwent manual small incision cataract surgery with intraocular
      lens implantation. Intraoperative complications included 1 posterior capsule
      rupture (1.2%). Six weeks following the treatment 98.6% of the operated patients
      achieved corrected distance visual acuity of 0.3 or better. Out of all 1296
      examined individuals, 224 (17.3%) presented visual impairment; 634 (24.5%) of the
      total number of eyes presented visual acuity of <0.3. In 90.2% of eyes the
      determinant of loss of sight was avoidable. CONCLUSION: High percentage of
      avoidable blindness, with the majority caused by cataract and refractive errors
      alone, indicate that appropriate programs focused on these diseases should be
      implemented. High volume cataract surgery in a camp setting with the application
      of appropriate surgical techniques and standardized protocols of disinfection and
      sterilization do not have to compromise on the quality of the outcome.

PMID- 23964180
TI  - Deep anterior lamellar keratoplasty for pellucid marginal degeneration.
AB  - PURPOSE: To present the surgical outcomes of deep anterior lamellar keratoplasty
      (DALK) for pellucid marginal degeneration (PMD). METHODS: A retrospective review
      was performed in 16 eyes of 16 patients who underwent DALK at the King Khaled Eye
      Specialist Hospital, Riyadh, Saudi Arabia between January 1, 2006 and December
      30, 2009. Baring of Descemet's membrane (DM) during DALK was achieved in 8 (50%)
      eyes; residual stroma was left intraoperatively in the remaining 8 (50%) eyes.
      The big bubble technique was performed in 10 (62.5%) eyes and manual dissection
      was performed in the remaining 6 (37.5%) eyes. Visual acuity (LogMAR notation),
      intraocular pressure, intraoperative complications and postoperative graft status
      were assessed. RESULTS: The mean follow up was 14.6 +/- 8.2 months (range 6-35
      months). The mean overall age was 31.4 +/- 9.6 years (range, 19-50 years). Visual
      acuity increased statistically significantly from 0.9 +/- 0.3 (range 0.5-1.6)
      preoperatively to 0.4 +/- 0.2 (range 0.0-0.7) at last follow-up (p < 0.0001).
      There was a statistically significant improvement in postoperative sphere,
      cylinder, and spherical equivalent (p < 0.035, p < 0.001, and p < 0.02,
      respectively) compared to preoperative. Postoperative visual acuity was not
      statistically significantly related to gender, type of surgical technique, and
      baring or perforation of DM. The main graft-related complication was graft-host
      vascularization (2/16 eyes). CONCLUSION: DALK reduces severe corneal astigmatism
      and results in good visual and refractive outcomes and is an effective
      alternative for patients with PMD.

PMID- 23964181
TI  - The outcome of the Ahmad Glaucoma Valve implantation for refractory glaucoma in
      Kuwait.
AB  - AIM: To assess the outcomes and incidence of postoperative complications of Ahmad
      Glaucoma Valve implant in eyes with complicated glaucoma performed in Kuwait.
      METHOD: This is a retrospective study done at the Al-Bahar Eye Center in Kuwait.
      Charts of all patients who underwent Ahmad Glaucoma Valve implant at the Al-Bahar
      Ophthalmic Center in Kuwait between 2006 and 2009 were reviewed. Surgical success
      was defined as intraocular pressure less than 22 mmHg and greater than 5 mmHg
      without additional glaucoma surgery and without loss of light perception.
      RESULTS: A total of 33 eyes from 30 patients with complicated glaucoma not
      responsive to conventional medical and non-implant surgical treatment received
      Ahmad Glaucoma Valve implant. The success rate was 79% (26 cases). 20/26 (77%)
      cases of them required antiglaucoma medications. The most common complication was
      encapsulated bleb (27%) and transient postoperative hypotony was found in 19% of
      the cases. CONCLUSION: Ahmad Glaucoma Valve implant appears to be effective and
      relatively safe for complicated glaucoma in Kuwait. The success rate is
      comparable with those reported in other studies.

PMID- 23964182
TI  - Discriminating ability of spectral domain optical coherence tomography in
      different stages of glaucoma.
AB  - PURPOSE: To determine the discriminating ability of retinal nerve fiber layer
      (RNFL) thickness measured with spectral-domain optical coherence tomography (SD
      OCT) in different stages of glaucoma. PATIENTS AND METHODS: Thirty normal, 150
      glaucomatous eyes were included. Glaucomatous eyes were graded into early,
      moderate and severe stages according to one of the global indices called visual
      field index (VFI). Complete ophthalmic examination, white on white perimetry and
      SD-OCT were done for all patients. RNFL thickness of quadrants and average
      thickness were recorded. Area under receiver operating characteristic curves
      (AUCs) were used to assess the performance of OCT parameters. RESULTS: AVERAGE,
      INFERIOR AND SUPERIOR RNFL THICKNESS WERE THE BEST PARAMETERS TO DISCRIMINATE
      NORMAL FROM EARLY GLAUCOMA (AUC: 0.91-86), early from moderate (AUC: 0.77-0.70)
      and moderate from severe (AUC: 0.85-83). Average RNFL loss was 18% in early
      glaucoma, 28% in moderate glaucoma and 41% in severe glaucoma. Early damage tends
      to be focal and in the lower quadrant. A significant correlation was detected
      between mean VFI and mean RNFL loss. Glaucoma was restaged according to average
      RNFL loss into early: ?97.5 MU, moderate: <97.5-72.5 MU and severe: <72.5 MU.
      CONCLUSION: RNFL thickness measured with SD-OCT could discriminate the three
      stages of glaucoma. RNFL loss can be correlated to visual field loss. Future OCT
      based staging of glaucoma, adjunctive to perimetry is possible.

PMID- 23964183
TI  - Intravitreal bevacizumab in persistent retinopathy secondary to malignant
      hypertension.
AB  - PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab (IVB)
      injection in persistent retinopathy secondary to malignant hypertension (MHT).
      PATIENTS AND METHODS: Single IVB injection of 1.25 mg/0.05 ml in 12 cases with
      persistent retinopathy secondary to MHT more than one month after control of MHT
      with pre and post injection evaluation of best corrected visual acuity (BCVA) and
      anatomical outcome up to sixth month and postinjection complications were
      evaluated. RESULTS: Progressive reductions in retinal hemorrhages, exudates,
      cotton-wool spots, and macular star were documented by photography, angiography,
      and central macular thickness (CMT) measured by optical coherence tomography
      (OCT) imaging. Decreased macular edema was the most common finding. Improvement
      or stabilization of visual acuity was noted in all cases. CONCLUSIONS: In
      addition to proper medical management of MHT, IVB injection is an effective and
      safe approach to treat persistent retinopathy associated with MHT.

PMID- 23964184
TI  - Comparison of clinical results between flap-on and flap-off techniques of
      epithelial-laser in situ keratomileusis in correction of low to moderate myopia
      in eyes with thin corneas.
AB  - PURPOSE: To prospectively compare flap-on and flap-off techniques of epithelial
      laser in situ keratomileusis (epi-LASIK) for the correction of low to moderate
      myopia in patients with thin corneas. METHODS: In this randomized, interventional
      study, the cohort was comprised of 88 eyes (44 patients) with myopia which
      underwent epi-LASIK. The epithelium was separated as a 9 mm flap with 2-4 mm
      nasal hinge with epikeratome (Lasatom, Gebauer Medizintechnik GmbH, Neuhausen,
      Germany) and the ablation was performed with the MEL 80 excimer laser (Carl
      Zeiss, Meditec, Jena, Germany). Thirty-eight eyes underwent flap-on Epi-LASIK
      where the flap was repositioned after ablation (flap-on group) and 50 eyes
      underwent flap-off Epi-LASIK where the epithelial flap was discarded (flap-off
      group). Pre- and post-operative uncorrected visual acuity (UCVA), best spectacle
      corrected visual acuity (BSCVA), and spherical equivalent (SE) were collected for
      each group. Post-operative pain, time to epithelialization, and corneal haze were
      also collected postoperatively. Variables were compared with the paired t-test,
      chi-squared test and one-way analysis of variance. Statistically significance was
      indicated by p < 0.05. RESULTS: The mean preoperative SE was -3.89 +/- 1.9
      diopters (D) for the flap-on group and -3.92 +/- 2.17 D for the flap-off group (p
      = 0.96). The mean follow-up was 12 months. The mean pain score was comparable on
      all postoperative days except the 2nd postoperative day where the flap-on had
      significantly lower mean pain scores (p = 00). Time for epithelial healing was
      4.39 +/- 0.49 days in flap-on group and 4.64 +/- 0.69 days in flap-off group (p =
      0.07). There was no significant difference in the postoperative UCVA between
      groups (p = 0.77). Corneal haze at the end of postoperative follow-up was not
      different between groups (p = 0.217). CONCLUSION: There is no significant
      difference in the clinical outcomes between flap-on and flap-off techniques of
      Epi-LASIK for the correction of low to moderate myopia.

PMID- 23964185
TI  - Regional anaesthesia for surgical repair in selected open globe injuries in
      adults.
AB  - PURPOSE: To determine whether the combination of topical, intracameral and facial
      nerve blocks would produce adequate analgesia for repair of open globe injuries
      without increasing intraocular tension. METHODS: A comparison of combined
      O'Brien's block (facial nerve block), topical ropivacaine and intracameral
      lignocaine versus peribulbar block in 100 randomly selected cases of traumatic
      corneal rupture. Patients were randomly divided in two groups of 50 each based on
      those receiving the combined approach (Group T) and those undergoing peribulbar
      block (Group P). Patients were excluded if there was rupture with significant
      scleral extension, the interval between trauma and presentation greater than 2 h,
      presence of hypopyon, rupture with significant corneal oedema, expulsion of
      intraocular contents with a collapsed globe and monocular cases. The effect of
      the anaesthetic was compared by patient comfort and surgeon comfort, the
      incidence of vitreous prolapse and the requirement of incremental sedation. The
      Student's "t" test, the "Z" test, and Chi Square tests were used where
      appropriate. P < 0.05 was considered statistically significant. RESULTS: The
      average patient comfort in Group P was 5.67% greater than Group T (P > 0.05). The
      average surgeon comfort and patient comfort between groups were similar (P >
      0.05, both comparisons). Incremental sedation was required in 16% of patients in
      Group T compared to 8% in Group P (P = 0.218363). The total sedation dosage
      required for each group was similar. The incidence of vitreous prolapse was
      statistically significantly higher by 14% in Group P compared to Group T (P =
      0.03731). CONCLUSIONS: Our combined technique proved as efficacious as peribulbar
      block in providing adequate local anaesthesia and reducing the incidence of
      vitreous prolapse. We recommend greater use of this technique for repair of open
      globe injuries especially in locations where full time anaesthesia services are
      not available.

PMID- 23964186
TI  - Vincenz Fukala (1847-1911) and the early history of clear-lens operations in high
      myopia.
AB  - Vincenz (Wincenty) Fukala, was born in 1847 in Zolkiew at Galicia in Poland,
      studied medicine and ophthalmology in Vienna in 1871. He was a pioneer in
      systematically extracting the clear crystalline lens in young patients with high
      myopia. He demonstrated the benefit to this group of increased visual acuity
      which enabled them to work and ophthalmologists gradually began to carry out
      surgery in high myopes worldwide. He persisted in operating despite the vigorous
      opposition of several authorities but, through sheer determination he convinced
      skeptics of the efficacy of his surgical method of lens dissection. He performed
      the first lens discission in 1887 and in 1894, he had successfully treated 44
      patients. The late complication of retinal detachment, which was not understood
      until years later, eventually led surgeons to abandon the procedure until the
      recent improvements in both lenticular and retinal surgery techniques that led to
      better prognosis. 

PMID- 23964187
TI  - Cytomegalovirus-related corneal endotheliitis: A review article.
AB  - Cytomegalovirus (CMV)-related corneal endotheliitis is an inflammation of the
      corneal endothelium caused by CMV. It typically presents as coin-shaped keratic
      precipitates (KPs), with or without corneal edema, in otherwise healthy
      individuals. It may be associated with anterior uveitis and raised intraocular
      pressure (IOP). Patients with CMV-related corneal endotheliitis respond to
      systemic and topical ganciclovir with the use of topical steroid. Making an
      accurate early diagnosis is crucial in preventing loss of corneal endothelial
      cells and unnecessary treatment resulting from misdiagnosis in these patients. 

PMID- 23964188
TI  - The eye and visual system in the preeclampsia/eclampsia syndrome: What to expect?
AB  - The preeclampsia/eclampsia syndrome is a multisystem disorder that can include
      cardiovascular changes, hematologic abnormalities, hepatic and renal impairment,
      and neurologic or cerebral manifestations. It also can affect the eye and visual
      pathways. Visual symptoms concern up to 25% of patients with severe preeclampsia
      and 50% of patients with eclampsia. This review discusses the ophthalmic
      complications of preeclampsia/eclampsia with focus on the hypertensive
      retinopathy, exudative retinal detachment and cortical blindness. 

PMID- 23964189
TI  - Acute bacterial endophthalmitis after intravitreal bevacizumab injection: Case
      report and literature review.
AB  - A case report of a 52 year old male who received intravitreal bevacizumab and
      developed culture positive endophthalmitis. Vitreous culture indicated that
      endophthalmitis was caused by Staphylococcus epidermidis. The patient was
      initially managed with intravitreal injection of ceftazidime and vancomycin,
      followed by pars plana lensectomy, pars plana vitrectomy with intravitreal
      injection of 1 mg/0.1 ml vancomycin, 2.25 mg/0.1 ml ceftazidime, 5 mg/0.1 ml
      fortified amphotericin-B and 4 mg/0.1 ml dexamethasone. Postoperatively the
      patient improved significantly. However, vision improved from hand motion to
      counting fingers secondary to severe retinal ischemia. Acute endophthalmitis can
      develop after intravitreal bevacizumab injections and cause profound visual loss.
      A review of literature was also performed for similar cases. 

PMID- 23964190
TI  - Erratum: Validation of patient symptom diary in acute posterior vitreous
      detachment.

PMID- 23964191
TI  - Primary bilateral small lymphocytic lymphoma of ocular adnexal origin: Imprint
      cytology suggests the intraoperative diagnosis.
AB  - Ocular adnexal lymphomas (OAL) involve the peri-global soft tissues like orbit,
      eyelid, conjunctiva, lacrimal gland. We describe a rare case of primary bilateral
      OAL, histomorphologically small lymphocytic lymphoma, B cell phenotype of
      lacrimal gland origin. Rapid intraoperative diagnosis can be suggested on imprint
      cytology; subsequent histology and immunohistochemistry are helpful for
      confirmation and further line of management. Since no preformed lymphoid
      structures are expected within the orbit or lacrimal gland, any lymphoid mass
      here should be critically evaluated as a lymphoproliferative lesion. 

PMID- 23964192
TI  - Band atrophy of the optic nerve: A report on different anatomical locations in
      three patients.
AB  - Lesions of the optic tract are accompanied by various signs that help to
      distinguish them from hemianopias located posterior to the lateral geniculate
      body. Band optic nerve atrophy is one of these signs and typically occurs
      contralateral to the optic tract lesion. We report on three patients with band
      atrophy in the fundus of the eye. These three patients present examples of how
      three lesions with different anatomic locations can cause band atrophy of the
      optic disk in similar ways. In these cases, the presence of relative afferent
      pupillary defect (RAPD) and band atrophy becomes important in identifying the
      injury to the optic tract, because when the hemianopia is complete visual fields
      do not allow distinguishing optic tract lesions from occipital lesions. The RAPD
      occurs in the eye in which the visual field defect is greater. In this paper we
      review the different theories about the explanation for RAPD in patients with
      optic tract lesions. It does not seem as simple as the anatomical differences
      between the number of fibers that decussate in particular cases, rather, it is
      associated with the difference between the sensitivity levels of the two
      functioning hemiretinas. 

PMID- 23964194
TI  - Integrated pest management with stochastic birth rate for prey species.
AB  - Song and Xiang (2006) developed an impulsive differential equations model for a
      two-prey one-predator model with stage structure for the predator. They
      demonstrate the conditions on the impulsive period for which a globally
      asymptotically stable pest-eradication periodic solution exists, as well as
      conditions on the impulsive period for which the prey species is permanently
      maintained under an economically acceptable threshold. We extend their model by
      including stage structure for both predator and prey as well as by adding
      stochastic elements in the birth rate of the prey. As in Song and Xiang (2006),
      we find the conditions under which a globally asymptotically stable pest
      eradication periodic solution exists. In addition, we numerically show the
      relationship between the stochastically varying birth rate of the prey and the
      necessary efficacy of the pesticide for which the probability of eradication of
      the prey species is above 90%. This is significant because the model recognizes
      varying environmental and climatic conditions which affect the resources needed
      for pest eradication. 

PMID- 23964193
TI  - A multi-site resting state fMRI study on the amplitude of low frequency
      fluctuations in schizophrenia.
AB  - BACKGROUND: This multi-site study compares resting state fMRI amplitude of low
      frequency fluctuations (ALFF) and fractional ALFF (fALFF) between patients with
      schizophrenia (SZ) and healthy controls (HC). METHODS: Eyes-closed resting fMRI
      scans (5:38 min; n = 306, 146 SZ) were collected from 6 Siemens 3T scanners and
      one GE 3T scanner. Imaging data were pre-processed using an SPM pipeline. Power
      in the low frequency band (0.01-0.08 Hz) was calculated both for the original pre
      processed data as well as for the pre-processed data after regressing out the six
      rigid-body motion parameters, mean white matter (WM) and cerebral spinal fluid
      (CSF) signals. Both original and regressed ALFF and fALFF measures were modeled
      with site, diagnosis, age, and diagnosis * age interactions. RESULTS: Regressing
      out motion and non-gray matter signals significantly decreased fALFF throughout
      the brain as well as ALFF in the cortical edge, but significantly increased ALFF
      in subcortical regions. Regression had little effect on site, age, and diagnosis
      effects on ALFF, other than to reduce diagnosis effects in subcortical regions.
      There were significant effects of site across the brain in all the analyses,
      largely due to vendor differences. HC showed greater ALFF in the occipital,
      posterior parietal, and superior temporal lobe, while SZ showed smaller clusters
      of greater ALFF in the frontal and temporal/insular regions as well as in the
      caudate, putamen, and hippocampus. HC showed greater fALFF compared with SZ in
      all regions, though subcortical differences were only significant for original
      fALFF. CONCLUSIONS: SZ show greater eyes-closed resting state low frequency power
      in frontal cortex, and less power in posterior lobes than do HC; fALFF, however,
      is lower in SZ than HC throughout the cortex. These effects are robust to multi
      site variability. Regressing out physiological noise signals significantly
      affects both total and fALFF measures, but does not affect the pattern of
      case/control differences.

PMID- 23964196
TI  - Development-related alternative splicing of PAC1 receptor: a key player in
      schizophrenia?

PMID- 23964195
TI  - Perinatal nutrition programs neuroimmune function long-term: mechanisms and
      implications.
AB  - Our early life nutritional environment can influence several aspects of
      physiology, including our propensity to become obese. There is now evidence to
      suggest perinatal diet can also independently influence development of our innate
      immune system. This review will address three not-necessarily-exclusive
      mechanisms by which perinatal nutrition can program neuroimmune function long
      term: by predisposing the individual to obesity, by altering the gut microbiota,
      and by inducing epigenetic modifications that alter gene transcription throughout
      life. 

PMID- 23964197
TI  - SVCT2 vitamin C transporter expression in progenitor cells of the postnatal
      neurogenic niche.
AB  - Known as a critical antioxidant, recent studies suggest that vitamin C plays an
      important role in stem cell generation, proliferation and differentiation.
      Vitamin C also enhances neural differentiation during cerebral development, a
      function that has not been studied in brain precursor cells. We observed that the
      rat neurogenic niche is structurally organized at day 15 of postnatal
      development, and proliferation and neural differentiation increase at day 21. In
      the human brain, a similar subventricular niche was observed at 1-month of
      postnatal development. Using immunohistochemistry, sodium-vitamin C cotransporter
      2 (SVCT2) expression was detected in the subventricular zone (SVZ) and rostral
      migratory stream (RMS). Low co-distribution of SVCT2 and betaIII-tubulin in
      neuroblasts or type-A cells was detected, and minimal co-localization of SVCT2
      and GFAP in type-B or precursor cells was observed. Similar results were obtained
      in the human neurogenic niche. However, BrdU-positive cells also expressed SVCT2,
      suggesting a role of vitamin C in neural progenitor proliferation. Primary
      neurospheres prepared from rat brain and the P19 teratocarcinoma cell line, which
      forms neurospheres in vitro, were used to analyze the effect of vitamin C in
      neural stem cells. Both cell types expressed functional SVCT2 in vitro, and
      ascorbic acid (AA) induced their neural differentiation, increased betaIII
      tubulin and SVCT2 expression, and amplified vitamin C uptake. 

PMID- 23964198
TI  - Thyroid hormone-dependent development of early cortical networks: temporal
      specificity and the contribution of trkB and mTOR pathways.
AB  - Early in neocortical network development, triiodothyronine (T3) promotes
      GABAergic neurons' population increase, their somatic growth and the formation of
      GABAergic synapses. In the presence of T3, GABAergic interneurons form longer
      axons and conspicuous axonal arborizations, with an increased number of putative
      synaptic boutons. Here we show that the increased GABAergic axonal growth is
      positively correlated with the proximity to non-GABAergic neurons (non-GABA). A
      differential innervation emerges from a T3-dependent decrease of axonal length in
      fields with low density of neuronal cell bodies, combined with an increased
      bouton formation in fields with high density of neuronal somata. T3 addition to
      deprived networks after the first 2 weeks of development did not rescue deficits
      in the GABAergic synaptic bouton distribution, or in the frequency and duration
      of spontaneous bursts. During the critical 2-week-period, GABAergic signaling is
      depolarizing as revealed by calcium imaging experiments. Interestingly, T3
      enhanced the expression of the potassium-chloride cotransporter 2 (KCC2), and
      accelerated the developmental shift from depolarizing to hyperpolarizing
      GABAergic signaling in non-GABA. The T3-related increase of spontaneous network
      activity was remarkably reduced after blockade of either tropomyosin-receptor
      kinase B (trkB) or mammalian target of rapamycin (mTOR) pathways. T3-dependent
      increase in GABAergic neurons' soma size was mediated mainly by mTOR signaling.
      Conversely, the T3-dependent selective increase of GABAergic boutons near non
      GABAergic cell bodies is mediated by trkB signaling only. Both trkB and mTOR
      signaling mediate T3-dependent reduction of the GABAergic axon extension. The
      circuitry context is relevant for the interaction between T3 and trkB signaling,
      but not for the interactions between T3 and mTOR signaling. 

PMID- 23964199
TI  - Environmental enrichment causes a global potentiation of neuronal responses
      across stimulus complexity and lamina of sensory cortex.
AB  - Enriched social and physical housing produces many molecular, anatomical,
      electrophysiological and behavior benefits even in adult animals. Much less is
      known of its effects on cortical electrophysiology, especially in how sensory
      cortex encodes the altered environment, and extant studies have generally been
      restricted to neurons in input laminae in sensory cortex. To extend the
      understanding of how an enriched environment alters the way in which cortex views
      the world, we investigated enrichment-induced changes in neuronal encoding of
      sensory stimuli across all laminae of the rat barrel cortex receiving input from
      the face whisker tactile system. Animals were housed in Enriched (n = 13) or
      Isolated housing (n = 13) conditions for 8 weeks before extracellular recordings
      were obtained from barrel cortex in response to simple whisker deflections and
      whisker motions modeling movements seen in awake animals undertaking a variety of
      different tasks. Enrichment resulted in increases in neuronal responses to all
      stimuli, ranging from those modeling exploratory behavior through to
      discrimination behaviors. These increases were seen throughout the cortex from
      supragranular layers through to input Layer 4 and for some stimuli, in
      infragranular Layer 5. The observed enrichment-induced effect is consistent with
      the postulate that enrichment causes shift in cortical excitatory/inhibitory
      balance, and we demonstrate this is greatest in supragranular layers. However, we
      also report that the effects are non-selective for stimulus parameters across a
      range of stimuli except for one modeling the likely use of whiskers by the rats
      in the enriched housing. 

PMID- 23964201
TI  - MicroRNAs in the axon and presynaptic nerve terminal.
AB  - The distal structural/functional domains of the neuron, to include the axon and
      presynaptic nerve terminal, contain a large, heterogeneous population of mRNAs
      and an active protein synthetic system. These local components of the genetic
      expression machinery play a critical role in the development, function, and long
      term viability of the neuron. In addition to the local mRNA populations these
      presynaptic domains contain a significant number of non-coding RNAs that regulate
      gene expression post-transcriptionally. Here, we review a small, but rapidly
      evolving literature on the composition and function of microRNAs that regulate
      gene expression locally in the axon and nerve terminal. In this capacity, these
      small regulatory RNAs have a profound effect on axonal protein synthesis, local
      energy metabolism, and the modulation of axonal outgrowth and branching. 

PMID- 23964200
TI  - Thyroid hormone treated astrocytes induce maturation of cerebral cortical neurons
      through modulation of proteoglycan levels.
AB  - Proper brain neuronal circuitry formation and synapse development is dependent on
      specific cues, either genetic or epigenetic, provided by the surrounding neural
      environment. Within these signals, thyroid hormones (T3 and T4) play crucial role
      in several steps of brain morphogenesis including proliferation of progenitor
      cells, neuronal differentiation, maturation, migration, and synapse formation.
      The lack of thyroid hormones during childhood is associated with several impair
      neuronal connections, cognitive deficits, and mental disorders. Many of the
      thyroid hormones effects are mediated by astrocytes, although the mechanisms
      underlying these events are still unknown. In this work, we investigated the
      effect of 3, 5, 3'-triiodothyronine-treated (T3-treated) astrocytes on cerebral
      cortex neuronal differentiation. Culture of neural progenitors from embryonic
      cerebral cortex mice onto T3-treated astrocyte monolayers yielded an increment in
      neuronal population, followed by enhancement of neuronal maturation, arborization
      and neurite outgrowth. In addition, real time PCR assays revealed an increase in
      the levels of the heparan sulfate proteoglycans, Glypican 1 (GPC-1) and Syndecans
      3 e 4 (SDC-3 e SDC-4), followed by a decrease in the levels of the chondroitin
      sulfate proteoglycan, Versican. Disruption of glycosaminoglycan chains by
      chondroitinase AC or heparanase III completely abolished the effects of T3
      treated astrocytes on neuronal morphogenesis. Our work provides evidence that
      astrocytes are key mediators of T3 actions on cerebral cortex neuronal
      development and identified potential molecules and pathways involved in neurite
      extension; which might eventually contribute to a better understanding of axonal
      regeneration, synapse formation, and neuronal circuitry recover. 

PMID- 23964202
TI  - New mechanism for glutamate hypothesis in epilepsy.

PMID- 23964203
TI  - Neural activity in mediodorsal nucleus of thalamus in rats performing a working
      memory task.
AB  - The neural circuit consisting of mediodorsal nucleus (MDN) of thalamus and
      prefrontal cortex (PFC) has been implicated in working memory. In order to
      investigate whether and how the rodent MDN processes working memory-related
      signals, we recorded activity of single neurons from the MDN in rats performing a
      delayed spatial alternation task. The MDN conveyed significant neural signals for
      the animal's previously chosen goal (retrospective information) in the early
      delay period, but the signals deteriorated gradually over time so that they
      became weak toward the end of the delay period. Neural signals for the animal's
      upcoming goal choice (prospective information) were even weaker than those for
      the previously chosen goal. These results are in contrast to the finding in
      monkeys that both MDN and PFC persistently maintain task-related neural signals
      throughout delay period. Our results do not support sustained MDN-PFC
      interactions as a general mechanism for mediating working memory across different
      behavioral tasks and/or animal species. 

PMID- 23964206
TI  - Mediodorsal thalamus and cognition in non-human primates.
AB  - Several recent studies in non-human primates have provided new insights into the
      role of the medial thalamus in different aspects of cognitive function. The
      mediodorsal nucleus of the thalamus (MD), by virtue of its connectivity with the
      frontal cortex, has been implicated in an array of cognitive functions. Rather
      than serving as an engine or relay for the prefrontal cortex, this area seems to
      be more specifically involved in regulating plasticity and flexibility of
      prefrontal-dependent cognitive functions. Focal damage to MD may also exacerbate
      the effects of damage to other subcortical relays. Thus, a wide range of
      distributed circuits and cognitive functions may be disrupted from focal damage
      within the medial thalamus (for example as a consequence of stroke or brain
      injury). Conversely, this region may make an interesting target for
      neuromodulation of cognitive function via deep brain stimulation or related
      methods, in conditions associated with dysfunction of these neural circuits. 

PMID- 23964204
TI  - Mind the fish: zebrafish as a model in cognitive social neuroscience.
AB  - Understanding how the brain implements social behavior on one hand, and how
      social processes feedback on the brain to promote fine-tuning of behavioral
      output according to changes in the social environment is a major challenge in
      contemporary neuroscience. A critical step to take this challenge successfully is
      finding the appropriate level of analysis when relating social to biological
      phenomena. Given the enormous complexity of both the neural networks of the brain
      and social systems, the use of a cognitive level of analysis (in an information
      processing perspective) is proposed here as an explanatory interface between
      brain and behavior. A conceptual framework for a cognitive approach to
      comparative social neuroscience is proposed, consisting of the following steps to
      be taken across different species with varying social systems: (1) identification
      of the functional building blocks of social skills; (2) identification of the
      cognitive mechanisms underlying the previously identified social skills; and (3)
      mapping these information processing mechanisms onto the brain. Teleost fish are
      presented here as a group of choice to develop this approach, given the diversity
      of social systems present in closely related species that allows for planned
      phylogenetic comparisons, and the availability of neurogenetic tools that allows
      the visualization and manipulation of selected neural circuits in model species
      such as the zebrafish. Finally, the state-of-the art of zebrafish social
      cognition and of the tools available to map social cognitive abilities to neural
      circuits in zebrafish are reviewed. 

PMID- 23964205
TI  - Functional role of ambient GABA in refining neuronal circuits early in postnatal
      development.
AB  - Early in development, gamma-aminobutyric acid (GABA), the primary inhibitory
      neurotransmitter in the mature brain, depolarizes and excites targeted neurons by
      an outwardly directed flux of chloride, resulting from the peculiar balance
      between the cation-chloride importer NKCC1 and the extruder KCC2. The low
      expression of KCC2 at birth leads to accumulation of chloride inside the cell and
      to the equilibrium potential for chloride positive respect to the resting
      membrane potential. GABA exerts its action via synaptic and extrasynaptic GABAA
      receptors mediating phasic and tonic inhibition, respectively. Here, recent data
      on the contribution of "ambient" GABA to the refinement of neuronal circuits in
      the immature brain have been reviewed. In particular, we focus on the
      hippocampus, where, prior to the formation of conventional synapses, GABA
      released from growth cones and astrocytes in a calcium- and SNARE (soluble N
      ethylmaleimide-sensitive-factor attachment protein receptor)-independent way,
      diffuses away to activate in a paracrine fashion extrasynaptic receptors
      localized on distal neurons. The transient increase in intracellular calcium
      following the depolarizing action of GABA leads to inhibition of DNA synthesis
      and cell proliferation. Tonic GABA exerts also a chemotropic action on cell
      migration. Later on, when synapses are formed, GABA spilled out from neighboring
      synapses, acting mainly on extrasynaptic alpha5, beta2, beta3, and gamma
      containing GABAA receptor subunits, provides the membrane depolarization
      necessary for principal cells to reach the window where intrinsic bursts are
      generated. These are instrumental in triggering calcium transients associated
      with network-driven giant depolarizing potentials which act as coincident
      detector signals to enhance synaptic efficacy at emerging GABAergic and
      glutamatergic synapses. 

PMID- 23964207
TI  - Simulating the effects of short-term synaptic plasticity on postsynaptic dynamics
      in the globus pallidus.
AB  - The rat globus pallidus (GP) is one of the nuclei of the basal ganglia and plays
      an important role in a variety of motor and cognitive processes. In vivo studies
      have shown that repetitive stimulation evokes complex modulations of GP activity.
      In vitro and computational studies have suggested that short-term synaptic
      plasticity (STP) could be one of the underlying mechanisms. The current study
      used simplified single compartment modeling to explore the possible effect of STP
      on the activity of GP neurons during low and high frequency stimulation (HFS). To
      do this we constructed a model of a GP neuron connected to a small network of
      neurons from the three major input sources to GP neurons: striatum (Str),
      subthalamic nucleus (STN) and GP collaterals. All synapses were implemented with
      a kinetic model of STP. The in vitro recordings of responses to low frequency
      repetitive stimulation were highly reconstructed, including rate changes and
      locking to the stimulus. Mainly involved were fast forms of plasticity which have
      been found at these synapses. The simulations were qualitatively compared to a
      data set previously recorded in vitro in our lab. Reconstructions of experimental
      responses to HFS required adding slower forms of plasticity to the STN and GP
      collateral synapses, as well as adding metabotropic receptors to the STN-GP
      synapses. These finding suggest the existence of as yet unreported slower short
      term dynamics in the GP. The computational model made additional predictions
      about GP activity during low and HFS that may further our understanding of the
      mechanisms underlying repetative stimulation of the GP. 

PMID- 23964209
TI  - Fetal cholinergic anti-inflammatory pathway and necrotizing enterocolitis: the
      brain-gut connection begins in utero.
AB  - Necrotizing enterocolitis (NEC) is an acute neonatal inflammatory disease that
      affects the intestine and may result in necrosis, systemic sepsis and multisystem
      organ failure. NEC affects 5-10% of all infants with birth weight <= 1500 g or
      gestational age less than 30 weeks. Chorioamnionitis (CA) is the main
      manifestation of pathological inflammation in the fetus and is strong associated
      with NEC. CA affects 20% of full-term pregnancies and upto 60% of preterm
      pregnancies and, notably, is often an occult finding. Intrauterine exposure to
      inflammatory stimuli may switch innate immunity cells such as macrophages to a
      reactive phenotype ("priming"). Confronted with renewed inflammatory stimuli
      during labour or postnatally, such sensitized cells can sustain a chronic or
      exaggerated production of proinflammatory cytokines associated with NEC (two-hit
      hypothesis). Via the cholinergic anti-inflammatory pathway, a neurally mediated
      innate anti-inflammatory mechanism, higher levels of vagal activity are
      associated with lower systemic levels of proinflammatory cytokines. This effect
      is mediated by the alpha7 subunit nicotinic acetylcholine receptor (alpha7nAChR)
      on macrophages. The gut is the most extensive organ innervated by the vagus
      nerve; it is also the primary site of innate immunity in the newborn. Here we
      review the mechanisms of possible neuroimmunological brain-gut interactions
      involved in the induction and control of antenatal intestinal inflammatory
      response and priming. We propose a neuroimmunological framework to (1) study the
      long-term effects of perinatal intestinal response to infection and (2) to
      uncover new targets for preventive and therapeutic intervention. 

PMID- 23964208
TI  - Hypothalamic neurohormones and immune responses.
AB  - The aim of this review is to provide a comprehensive examination of the current
      literature describing the neural-immune interactions, with emphasis on the most
      recent findings of the effects of neurohormones on immune system. Particularly,
      the role of hypothalamic hormones such as Thyrotropin-releasing hormone (TRH),
      Corticotropin-releasing hormone (CRH) and Gonadotropin-releasing hormone (GnRH).
      In the past few years, interest has been raised in extrapituitary actions of
      these neurohormones due to their receptors have been found in many non-pituitary
      tissues. Also, the receptors are present in immune cells, suggesting an autocrine
      or paracrine role within the immune system. In general, these neurohormones have
      been reported to exert immunomodulatory effects on cell proliferation, immune
      mediators release and cell function. The implications of these findings in
      understanding the network of hypothalamic neuropeptides and immune system are
      discussed. 

PMID- 23964210
TI  - Finding synchrony in the desynchronized EEG: the history and interpretation of
      gamma rhythms.
AB  - Neocortical gamma (30-80 Hz) rhythms correlate with attention, movement and
      perception and are often disrupted in neurological and psychiatric disorders.
      Gamma primarily occurs during alert brain states characterized by the so-called
      "desynchronized" EEG. Is this because gamma rhythms are devoid of synchrony? In
      this review we take a historical approach to answering this question. Richard
      Caton and Adolf Beck were the first to report the rhythmic voltage fluctuations
      in the animal brain. They were limited by the poor amplification of their early
      galvanometers. Thus when they presented light or other stimuli, they observed a
      disappearance of the large resting oscillations. Several groups have since shown
      that visual stimuli lead to low amplitude gamma rhythms and that groups of
      neurons in the visual cortices fire together during individual gamma cycles. This
      synchronous firing can more strongly drive downstream neurons. We discuss how
      gamma-band synchrony can support ongoing communication between brain regions, and
      highlight an important fact: there is at least local neuronal synchrony during
      gamma rhythms. Thus, it is best to refer to the low amplitude, high frequency EEG
      as an "activated", not "desynchronized", EEG. 

PMID- 23964213
TI  - N-Methyl-d-Aspartate Receptor - Nitric Oxide Synthase Pathway in the Cortex of
      Nogo-A-Deficient Rats in Relation to Brain Laterality and Schizophrenia.
AB  - It has been suggested that Nogo-A, a myelin-associated protein, could play a role
      in the pathogenesis of schizophrenia and that Nogo-A-deficient rodents could
      serve as an animal model for schizophrenic symptoms. Since changes in brain
      laterality are typical of schizophrenia, we investigated whether Nogo-A-deficient
      rats showed any signs of disturbed asymmetry in cortical N-methyl-d-aspartate
      (NMDA) receptor-nitric oxide synthase (NOS) pathway, which is reported as
      dysfunctional in schizophrenia. In particular, we measured separately in the
      right and left hemisphere of young and old Nogo-A-deficient male rats the
      expression of NMDA receptor subunits (NR1, NR2A, and NR2B in the frontal cortex)
      and activities of NOS isoforms [neuronal (nNOS), endothelial (eNOS), and
      inducible (iNOS) in the parietal cortex]. In young controls, we observed
      right/left asymmetry of iNOS activity and three positive correlations (between
      NR1 in the left and NR2B laterality, between NR2B in the right and left sides,
      and between NR1 in the right side and nNOS laterality). In old controls, we found
      bilateral decreases in NR1, an increase in NR2B in the right side, and two
      changes in correlations in the NR1-nNOS pathway. In young Nogo-A-deficient rats,
      we observed an increase in iNOS activity in the left hemisphere and two changes
      in correlations in NR1-nNOS and NR2A-eNOS, compared to young controls. Finally,
      we revealed in old Nogo-A-deficient animals, bilateral decreases in NR1 and one
      change in correlation between eNOS-iNOS, compared to old controls. Although some
      findings from schizophrenic brains did not manifest in Nogo-A-deficient rats
      (e.g., no alterations in NR2B), others did (e.g., alterations demonstrating
      accelerated aging in young but not old animals, those occurring exclusively in
      the right hemisphere in young and old animals and those suggesting abnormal
      frontoparietal cortical interactions in young animals). 

PMID- 23964214
TI  - Stimulation of cell proliferation in the subventricular zone by synthetic murine
      pheromones.
AB  - Adult neurogenesis in female mice is known to be enhanced by exposure to soiled
      bedding from males, although the identity of the relevant chemosignals has
      remained unknown. Here we show that the previously recognized male murine
      pheromones, the farnesenes and 2-sec-butyl-4,5-dihydrothiazole (SBT), strongly
      increase cell proliferation in the subventricular zone (SVZ) of adult female
      mice, but not younger female mice. In addition, we found that a unique female
      murine pheromone, 2,5-dimethylpyrazine, facilitates similar changes in males. SBT
      stimulated cell proliferation in the SVZ of only adult females and not in young
      adult or pre- and post-puberty females. Our study suggests that pheromonal
      communication between males and females is enhancing reproductive success by
      controlling the estrous cycle and by promoting cell proliferation in a reciprocal
      manner. 

PMID- 23964212
TI  - Neural control of chronic stress adaptation.
AB  - Stress initiates adaptive processes that allow the organism to physiologically
      cope with prolonged or intermittent exposure to real or perceived threats. A
      major component of this response is repeated activation of glucocorticoid
      secretion by the hypothalamo-pituitary-adrenocortical (HPA) axis, which promotes
      redistribution of energy in a wide range of organ systems, including the brain.
      Prolonged or cumulative increases in glucocorticoid secretion can reduce benefits
      afforded by enhanced stress reactivity and eventually become maladaptive. The
      long-term impact of stress is kept in check by the process of habituation, which
      reduces HPA axis responses upon repeated exposure to homotypic stressors and
      likely limits deleterious actions of prolonged glucocorticoid secretion.
      Habituation is regulated by limbic stress-regulatory sites, and is at least in
      part glucocorticoid feedback-dependent. Chronic stress also sensitizes reactivity
      to new stimuli. While sensitization may be important in maintaining response
      flexibility in response to new threats, it may also add to the cumulative impact
      of glucocorticoids on the brain and body. Finally, unpredictable or severe stress
      exposure may cause long-term and lasting dysregulation of the HPA axis, likely
      due to altered limbic control of stress effector pathways. Stress-related
      disorders, such as depression and PTSD, are accompanied by glucocorticoid
      imbalances and structural/ functional alterations in limbic circuits that
      resemble those seen following chronic stress, suggesting that inappropriate
      processing of stressful information may be part of the pathological process. 

PMID- 23964211
TI  - Inflammatory process in Alzheimer's Disease.
AB  - Alzheimer Disease (AD) is a neurodegenerative disorder and the most common form
      of dementia. Histopathologically is characterized by the presence of two major
      hallmarks, the intracellular neurofibrillary tangles (NFTs) and extracellular
      neuritic plaques (NPs) surrounded by activated astrocytes and microglia. NFTs
      consist of paired helical filaments of truncated tau protein that is abnormally
      hyperphosphorylated. The main component in the NP is the amyloid-beta peptide
      (Abeta), a small fragment of 40-42 amino acids with a molecular weight of 4 kD.
      It has been proposed that the amyloid aggregates and microglia activation are
      able to favor the neurodegenerative process observed in AD patients. However, the
      role of inflammation in AD is controversial, because in early stages the
      inflammation could have a beneficial role in the pathology, since it has been
      thought that the microglia and astrocytes activated could be involved in Abeta
      clearance. Nevertheless the chronic activation of the microglia has been related
      with an increase of Abeta and possibly with tau phosphorylation. Studies in AD
      brains have shown an upregulation of complement molecules, pro-inflammatory
      cytokines, acute phase reactants and other inflammatory mediators that could
      contribute with the neurodegenerative process. Clinical trials and animal models
      with non-steroidal anti-inflammatory drugs (NSAIDs) indicate that these drugs may
      decrease the risk of developing AD and apparently reduce Abeta deposition.
      Finally, further studies are needed to determine whether treatment with anti
      inflammatory strategies, may decrease the neurodegenerative process that affects
      these patients. 

PMID- 23964215
TI  - Deep brain stimulation of the ventral striatum increases BDNF in the fear
      extinction circuit.
AB  - Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS)
      reduces the symptoms of treatment-resistant obsessive compulsive disorder (OCD),
      and improves response to extinction-based therapies. We recently reported that
      DBS-like stimulation of a rat homologue of VC/VS, the dorsal-VS, reduced
      conditioned fear and enhanced extinction memory (Rodriguez-Romaguera et al.,
      2012). In contrast, DBS of the ventral-VS had the opposite effects. To examine
      possible mechanisms of these effects, we assessed the effects of VS DBS on the
      expression of the neural activity marker Fos and brain-derived neurotrophic
      factor (BDNF), a key mediator of extinction plasticity in prefrontal-amygdala
      circuits. Consistent with decreased fear expression, DBS of dorsal-VS increased
      Fos expression in prelimbic and infralimbic prefrontal cortices and in the
      lateral division of the central nucleus of amygdala, an area that inhibits
      amygdala output. Consistent with improved extinction memory, we found that DBS of
      dorsal-VS, but not ventral-VS, increased neuronal BDNF expression in prelimbic
      and infralimbic prefrontal cortices. These rodent findings are consistent with
      the idea that clinical DBS of VC/VS may augment fear extinction through an
      increase in BDNF expression. 

PMID- 23964216
TI  - Competitive Trace Theory: A Role for the Hippocampus in Contextual Interference
      during Retrieval.
AB  - Much controversy exists regarding the role of the hippocampus in retrieval. The
      two dominant and competing accounts have been the Standard Model of Systems
      Consolidation (SMSC) and Multiple Trace Theory (MTT), which specifically make
      opposing predictions as to the necessity of the hippocampus for retrieval of
      remote memories. Under SMSC, memories eventually become independent of the
      hippocampus as they become more reliant on cortical connectivity, and thus the
      hippocampus is not required for retrieval of remote memories, only recent ones.
      MTT on the other hand claims that the hippocampus is always required no matter
      the age of the memory. We argue that this dissociation may be too simplistic, and
      a continuum model may be better suited to address the role of the hippocampus in
      retrieval of remote memories. Such a model is presented here with the main
      function of the hippocampus during retrieval being "recontextualization," or the
      reconstruction of memory using overlapping traces. As memories get older, they
      are decontextualized due to competition among partially overlapping traces and
      become more semantic and reliant on neocortical storage. In this framework dubbed
      the Competitive Trace Theory (CTT), consolidation events that lead to the
      strengthening of memories enhance conceptual knowledge (semantic memory) at the
      expense of contextual details (episodic memory). As a result, remote memories are
      more likely to have a stronger semantic representation. At the same time, remote
      memories are also more likely to include illusory details. The CTT is a novel
      candidate model that may provide some resolution to the memory consolidation
      debate. 

PMID- 23964217
TI  - Traumatic brain injury, neuroimaging, and neurodegeneration.
AB  - Depending on severity, traumatic brain injury (TBI) induces immediate
      neuropathological effects that in the mildest form may be transient but as
      severity increases results in neural damage and degeneration. The first phase of
      neural degeneration is explainable by the primary acute and secondary
      neuropathological effects initiated by the injury; however, neuroimaging studies
      demonstrate a prolonged period of pathological changes that progressively occur
      even during the chronic phase. This review examines how neuroimaging may be used
      in TBI to understand (1) the dynamic changes that occur in brain development
      relevant to understanding the effects of TBI and how these relate to
      developmental stage when the brain is injured, (2) how TBI interferes with age
      typical brain development and the effects of aging thereafter, and (3) how TBI
      results in greater frontotemporolimbic damage, results in cerebral atrophy, and
      is more disruptive to white matter neural connectivity. Neuroimaging
      quantification in TBI demonstrates degenerative effects from brain injury over
      time. An adverse synergistic influence of TBI with aging may predispose the brain
      injured individual for the development of neuropsychiatric and neurodegenerative
      disorders long after surviving the brain injury. 

PMID- 23964218
TI  - Theory of mind: mechanisms, methods, and new directions.
AB  - Theory of Mind (ToM) has received significant research attention. Traditional ToM
      research has provided important understanding of how humans reason about mental
      states by utilizing shared world knowledge, social cues, and the interpretation
      of actions; however, many current behavioral paradigms are limited to static,
      "third-person" protocols. Emerging experimental approaches such as cognitive
      simulation and simulated social interaction offer opportunities to investigate
      ToM in interactive, "first-person" and "second-person" scenarios while affording
      greater experimental control. The advantages and limitations of traditional and
      emerging ToM methodologies are discussed with the intent of advancing the
      understanding of ToM in socially mediated situations. 

PMID- 23964219
TI  - Varying expectancies and attention bias in phobic and non-phobic individuals.
AB  - Phobic individuals display an attention bias to phobia-related information and
      biased expectancies regarding the likelihood of being faced with such stimuli.
      Notably, although attention and expectancy biases are core features in phobia and
      anxiety disorders, these biases have mostly been investigated separately and
      their causal impact has not been examined. We hypothesized that these biases
      might be causally related. Spider phobic and low spider fearful control
      participants performed a visual search task in which they specified whether the
      deviant animal in a search array was a spider or a bird. Shorter reaction times
      (RTs) for spiders than for birds in this task reflect an attention bias toward
      spiders. Participants' expectancies regarding the likelihood of these animals
      being the deviant in the search array were manipulated by presenting verbal cues.
      Phobics were characterized by a pronounced and persistent attention bias toward
      spiders; controls displayed slower RTs for birds than for spiders only when
      spider cues had been presented. More important, we found RTs for spider
      detections to be virtually unaffected by the expectancy cues in both groups,
      whereas RTs for bird detections showed a clear influence of the cues. Our results
      speak to the possibility that evolution has formed attentional systems that are
      specific to the detection of phylogenetically salient stimuli such as threatening
      animals; these systems may not be as penetrable to variations in (experimentally
      induced) expectancies as those systems that are used for the detection of non
      threatening stimuli. In sum, our findings highlight the relation between
      expectancies and attention engagement in general. However, expectancies may play
      a greater role in attention engagement in safe environments than in threatening
      environments. 

PMID- 23964220
TI  - The effects of breakfast on behavior and academic performance in children and
      adolescents.
AB  - Breakfast consumption is associated with positive outcomes for diet quality,
      micronutrient intake, weight status and lifestyle factors. Breakfast has been
      suggested to positively affect learning in children in terms of behavior,
      cognitive, and school performance. However, these assertions are largely based on
      evidence which demonstrates acute effects of breakfast on cognitive performance.
      Less research which examines the effects of breakfast on the ecologically valid
      outcomes of academic performance or in-class behavior is available. The
      literature was searched for articles published between 1950-2013 indexed in Ovid
      MEDLINE, Pubmed, Web of Science, the Cochrane Library, EMBASE databases, and
      PsychINFO. Thirty-six articles examining the effects of breakfast on in-class
      behavior and academic performance in children and adolescents were included. The
      effects of breakfast in different populations were considered, including
      undernourished or well-nourished children and adolescents from differing socio
      economic status (SES) backgrounds. The habitual and acute effects of breakfast
      and the effects of school breakfast programs (SBPs) were considered. The evidence
      indicated a mainly positive effect of breakfast on on-task behavior in the
      classroom. There was suggestive evidence that habitual breakfast (frequency and
      quality) and SBPs have a positive effect on children's academic performance with
      clearest effects on mathematic and arithmetic grades in undernourished children.
      Increased frequency of habitual breakfast was consistently positively associated
      with academic performance. Some evidence suggested that quality of habitual
      breakfast, in terms of providing a greater variety of food groups and adequate
      energy, was positively related to school performance. However, these associations
      can be attributed, in part, to confounders such as SES and to methodological
      weaknesses such as the subjective nature of the observations of behavior in
      class. 

PMID- 23964222
TI  - Effortless awareness: using real time neurofeedback to investigate correlates of
      posterior cingulate cortex activity in meditators' self-report.
AB  - Neurophenomenological studies seek to utilize first-person self-report to
      elucidate cognitive processes related to physiological data. Grounded theory
      offers an approach to the qualitative analysis of self-report, whereby
      theoretical constructs are derived from empirical data. Here we used grounded
      theory methodology (GTM) to assess how the first-person experience of meditation
      relates to neural activity in a core region of the default mode network-the
      posterior cingulate cortex (PCC). We analyzed first-person data consisting of
      meditators' accounts of their subjective experience during runs of a real time
      fMRI neurofeedback study of meditation, and third-person data consisting of
      corresponding feedback graphs of PCC activity during the same runs. We found that
      for meditators, the subjective experiences of "undistracted awareness" such as
      "concentration" and "observing sensory experience," and "effortless doing" such
      as "observing sensory experience," "not efforting," and "contentment," correspond
      with PCC deactivation. Further, the subjective experiences of "distracted
      awareness" such as "distraction" and "interpreting," and "controlling" such as
      "efforting" and "discontentment," correspond with PCC activation. Moreover, we
      derived several novel hypotheses about how specific qualities of cognitive
      processes during meditation relate to PCC activity, such as the difference
      between meditation and "trying to meditate." These findings offer novel insights
      into the relationship between meditation and mind wandering or self-related
      thinking and neural activity in the default mode network, driven by first-person
      reports. 

PMID- 23964221
TI  - Functional and structural connectivity of frontostriatal circuitry in Autism
      Spectrum Disorder.
AB  - Abnormalities in frontostriatal circuitry potentially underlie the two core
      deficits in Autism Spectrum Disorder (ASD); social interaction and communication
      difficulties and restricted interests and repetitive behaviors. Whilst a few
      studies have examined connectivity within this circuitry in ASD, no previous
      study has examined both functional and structural connectivity within the same
      population. The present study provides the first exploration of both functional
      and structural frontostriatal connectivity in ASD. Twenty-eight right-handed
      Caucasian male ASD (17.28 +/- 3.57 years) and 27 right-handed male, age and IQ
      matched controls (17.15 +/- 3.64 years) took part in the study. Resting state
      functional connectivity was carried out on 21 ASD and control participants, and
      tractography was carried out on 22 ASD and 24 control participants, after
      excluding subjects for excessive motion and poor data quality. Functional
      connectivity analysis was carried out between the frontal cortex and striatum
      after which tractography was performed between regions that showed significant
      group differences in functional connectivity. The ASD group showed increased
      functional connectivity between regions in the frontal cortex [anterior cingulate
      cortex (ACC), middle frontal gyrus (MFG), paracingulate gyrus (Pcg) and
      orbitofrontal cortex (OFC)], and striatum [nucleus accumbens (NAcc) and caudate].
      Increased functional connectivity between ACC and caudate was associated with
      deactivation to social rewards in the caudate, as previously reported in the same
      participants. Greater connectivity between the right MFG and caudate was
      associated with higher restricted interests and repetitive behaviors and
      connectivity between the bilateral Pcg and NAcc, and the right OFC and NAcc, was
      negatively associated with social and communicative deficits. Although tracts
      were reliably constructed for each subject, there were no group differences in
      structural connectivity. Results are in keeping with previously reported
      increased corticostriatal functional connectivity in ASD. 

PMID- 23964223
TI  - Functional connectivity in the first year of life in infants at-risk for autism:
      a preliminary near-infrared spectroscopy study.
AB  - BACKGROUND: Autism spectrum disorder (ASD) has been called a "developmental
      disconnection syndrome," however the majority of the research examining
      connectivity in ASD has been conducted exclusively with older children and
      adults. Yet, prior ASD research suggests that perturbations in neurodevelopmental
      trajectories begin as early as the first year of life. Prospective longitudinal
      studies of infants at risk for ASD may provide a window into the emergence of
      these aberrant patterns of connectivity. The current study employed functional
      connectivity near-infrared spectroscopy (NIRS) in order to examine the
      development of intra- and inter-hemispheric functional connectivity in high- and
      low-risk infants across the first year of life. METHODS: NIRS data were collected
      from 27 infants at high risk for autism (HRA) and 37 low-risk comparison (LRC)
      infants who contributed a total of 116 data sets at 3-, 6-, 9-, and 12-months. At
      each time point, HRA and LRC groups were matched on age, sex, head circumference,
      and Mullen Scales of Early Learning scores. Regions of interest (ROI) were
      selected from anterior and posterior locations of each hemisphere. The average
      time course for each ROI was calculated and correlations for each ROI pair were
      computed. Differences in functional connectivity were examined in a cross
      sectional manner. RESULTS: At 3-months, HRA infants showed increased overall
      functional connectivity compared to LRC infants. This was the result of increased
      connectivity for intra- and inter-hemispheric ROI pairs. No significant
      differences were found between HRA and LRC infants at 6- and 9-months. However,
      by 12-months, HRA infants showed decreased connectivity relative to LRC infants.
      CONCLUSIONS: Our preliminary results suggest that atypical functional
      connectivity may exist within the first year of life in HRA infants, providing
      support to the growing body of evidence that aberrant patterns of connectivity
      may be a potential endophenotype for ASD.

PMID- 23964224
TI  - Neuroimaging, a new tool for investigating the effects of early diet on cognitive
      and brain development.
AB  - Nutrition is crucial to the initial development of the central nervous system
      (CNS), and then to its maintenance, because both depend on dietary intake to
      supply the elements required to develop and fuel the system. Diet in early life
      is often seen in the context of "programming" where a stimulus occurring during a
      vulnerable period can have long-lasting or even lifetime effects on some aspect
      of the organism's structure or function. Nutrition was first shown to be a
      programming stimulus for growth, and then for cognitive behavior, in animal
      studies that were able to employ methods that allowed the demonstration of neural
      effects of early nutrition. Such research raised the question of whether
      nutrition could also programme cognition/brain structure in humans. Initial
      studies of cognitive effects were observational, usually conducted in developing
      countries where the presence of confounding factors made it difficult to
      interpret the role of nutrition in the cognitive deficits that were seen.
      Attributing causality to nutrition required randomized controlled trials (RCTs)
      and these, often in developed countries, started to appear around 30 years ago.
      Most demonstrated convincingly that early nutrition could affect subsequent
      cognition. Until the advent of neuroimaging techniques that allowed in vivo
      examination of the brain, however, we could determine very little about the
      neural effects of early diet in humans. The combination of well-designed trials
      with neuroimaging tools means that we are now able to pose and answer questions
      that would have seemed impossible only recently. This review discusses various
      neuroimaging methods that are suitable for use in nutrition studies, while
      pointing out some of the limitations that they may have. The existing literature
      is small, but examples of studies that have used these methods are presented.
      Finally, some considerations that have arisen from previous studies, as well as
      suggestions for future research, are discussed. 

PMID- 23964225
TI  - The Amsterdam Resting-State Questionnaire reveals multiple phenotypes of resting
      state cognition.
AB  - Resting-state neuroimaging is a dominant paradigm for studying brain function in
      health and disease. It is attractive for clinical research because of its
      simplicity for patients, straightforward standardization, and sensitivity to
      brain disorders. Importantly, non-sensory experiences like mind wandering may
      arise from ongoing brain activity. However, little is known about the link
      between ongoing brain activity and cognition, as phenotypes of resting-state
      cognition-and tools to quantify them-have been lacking. To facilitate rapid and
      structured measurements of resting-state cognition we developed a 50-item self
      report survey, the Amsterdam Resting-State Questionnaire (ARSQ). Based on ARSQ
      data from 813 participants assessed after 5 min eyes-closed rest in their home,
      we identified seven dimensions of resting-state cognition using factor analysis:
      Discontinuity of Mind, Theory of Mind, Self, Planning, Sleepiness, Comfort, and
      Somatic Awareness. Further, we showed that the structure of cognition was similar
      during resting-state fMRI and EEG, and that the test-retest correlations were
      remarkably high for all dimensions. To explore whether inter-individual variation
      of resting-state cognition is related to health status, we correlated ARSQ
      derived factor scores with psychometric scales measuring depression, anxiety, and
      sleep quality. Mental health correlated positively with Comfort and negatively
      with Discontinuity of Mind. Finally, we show that sleepiness may partially
      explain a resting-state EEG profile previously associated with Alzheimer's
      disease. These findings indicate that the ARSQ readily provides information about
      cognitive phenotypes and that it is a promising tool for research on the neural
      correlates of resting-state cognition in health and disease. 

PMID- 23964226
TI  - Violence as a source of pleasure or displeasure is associated with specific
      functional connectivity with the nucleus accumbens.
AB  - The appraisal of violent stimuli is dependent on the social context and the
      perceiver's individual characteristics. To identify the specific neural circuits
      involved in the perception of violent videos, forty-nine male participants were
      scanned with functional MRI while watching video-clips depicting Mixed Martial
      Arts (MMA) and Capoeira as a baseline. Prior to scanning, a self-report measure
      of pleasure or displeasure when watching MMA was collected. Watching MMA was
      associated with activation of the anterior insula (AI), brainstem, ventral
      tegmental area (VTA), striatum, medial, and lateral prefrontal cortex,
      orbitofrontal cortex, somatosensory cortex, and supramarginal gyrus. While this
      pattern of brain activation was not related to participants' reported experience
      of pleasure or displeasure, pleasurable ratings of MMA predicted increased
      functional connectivity (FC) seeded in the nucleus accumbens (NAcc) (a structure
      known to be responsive to anticipating both positive and negative outcomes) with
      the subgenual anterior cingulate cortex (ACC) and anterior insular cortex (AIC)
      (regions involved in positive feelings and visceral somatic representations).
      Displeasure ratings of MMA were related to increased FC with regions of the
      prefrontal cortex and superior parietal lobule, structures implicated in
      cognitive control and executive attention. These data suggest that functional
      connectivity is an effective approach to investigate the relationship between
      subjective feelings of pleasure and pain of neural structures known to respond to
      both the anticipation of positive and negative outcomes. 

PMID- 23964228
TI  - Through your eyes: incongruence of gaze and action increases spontaneous
      perspective taking.
AB  - What makes people spontaneously adopt the perspective of others? Previous work
      suggested that perspective taking can serve understanding the actions of others.
      Two studies corroborate and extend that interpretation. The first study varied
      cues to intentionality of eye gaze and action, and found that the more the actor
      was perceived as potentially interacting with the objects, the stronger the
      tendency to take his perspective. The second study investigated how manipulations
      of gaze affect the tendency to adopt the perspective of another reaching for an
      object. Eliminating gaze cues by blurring the actor's face did not reduce
      perspective-taking, suggesting that in the absence of gaze information, observers
      rely entirely on the action. Intriguingly, perspective-taking was higher when
      gaze and action did not signal the same intention, suggesting that in presence of
      ambiguous behavioral intention, people are more likely take the other's
      perspective to try to understand the action. 

PMID- 23964229
TI  - Strategy modulates spatial perspective-taking: evidence for dissociable
      disembodied and embodied routes.
AB  - Previous research provides evidence for a dissociable embodied route to spatial
      perspective-taking that is under strategic control. The present experiment
      investigated further the influence of strategy on spatial perspective-taking by
      assessing whether participants may also elect to employ a separable "disembodied"
      route loading on inhibitory control mechanisms. Participants (N = 92) undertook
      both the "own body transformation" (OBT) perspective-taking task, requiring
      speeded spatial judgments made from the perspective of an observed figure, and a
      control task measuring ability to inhibit spatially compatible responses in the
      absence of a figure. Perspective-taking performance was found to be related to
      performance on the response inhibition control task, in that participants who
      tended to take longer to adopt a new perspective also tended to show a greater
      elevation in response times when inhibiting spatially compatible responses. This
      relationship was restricted to those participants reporting that they adopted the
      perspective of another by reversing left and right whenever confronted with a
      front-view figure; it was absent in those participants who reported perspective
      taking by mentally transforming their spatial orientation to align with that of
      the figure. Combined with previously published results, these findings complete a
      double dissociation between embodied and disembodied routes to spatial
      perspective-taking, implying that spatial perspective-taking is subject to
      modulation by strategy, and suggesting that embodied routes to perspective-taking
      may place minimal demands on domain general executive functions. 

PMID- 23964231
TI  - The application of near infrared spectroscopy in nutritional intervention
      studies.
AB  - Functional near infrared spectroscopy (NIRS) is a non-invasive optical imaging
      technique used to monitor cerebral blood flow (CBF) and by proxy neuronal
      activation. The use of NIRS in nutritional intervention studies is a relatively
      novel application of this technique, with only a small, but growing, number of
      trials published to date. These trials-in which the effects on CBF following
      administration of dietary components such as caffeine, polyphenols and omega-3
      polyunsaturated fatty acids are assessed-have successfully demonstrated NIRS as a
      sensitive measure of change in hemodynamic response during cognitive tasks in
      both acute and chronic treatment intervention paradigms. The existent research in
      this area has been limited by the constraints of the technique itself however
      advancements in the measurement technology, paired with studies endeavoring
      increased sophistication in number and locations of channels over the head should
      render the use of NIRS in nutritional interventions particularly valuable in
      advancing our understanding of the effects of nutrients and dietary components on
      the brain. 

PMID- 23964230
TI  - Continuities in emotion lateralization in human and non-human primates.
AB  - Where hemispheric lateralization was once considered an exclusively human trait,
      it is increasingly recognized that hemispheric asymmetries are evident throughout
      the animal kingdom. Emotion is a prime example of a lateralized function: given
      its vital role in promoting adaptive behavior and hence survival, a growing body
      of research in affective neuroscience is working to illuminate the cortical bases
      of emotion processing. Presuming that human and non-human primates evolved from a
      shared ancestor, one would anticipate evidence of organizational continuity in
      the neural substrate supporting emotion processing. This paper thus reviews
      research examining the patterns of lateralization for the expression and
      perception of facial emotion in non-human primates, aiming to determine whether
      the patterns of hemispheric asymmetry that characterize the human brain are
      similarly evident in other primate species. As such, this review seeks to enhance
      understanding of the evolution of hemispheric specialization for emotion, using
      emotion lateralization in non-human primates as a window through which to view
      emotion lateralization in humans. 

PMID- 23964232
TI  - The number and choice of muscles impact the results of muscle synergy analyses.
AB  - One theory for how humans control movement is that muscles are activated in
      weighted groups or synergies. Studies have shown that electromyography (EMG) from
      a variety of tasks can be described by a low-dimensional space thought to reflect
      synergies. These studies use algorithms, such as nonnegative matrix
      factorization, to identify synergies from EMG. Due to experimental constraints,
      EMG can rarely be taken from all muscles involved in a task. However, it is
      unclear if the choice of muscles included in the analysis impacts estimated
      synergies. The aim of our study was to evaluate the impact of the number and
      choice of muscles on synergy analyses. We used a musculoskeletal model to
      calculate muscle activations required to perform an isometric upper-extremity
      task. Synergies calculated from the activations from the musculoskeletal model
      were similar to a prior experimental study. To evaluate the impact of the number
      of muscles included in the analysis, we randomly selected subsets of between 5
      and 29 muscles and compared the similarity of the synergies calculated from each
      subset to a master set of synergies calculated from all muscles. We determined
      that the structure of synergies is dependent upon the number and choice of
      muscles included in the analysis. When five muscles were included in the
      analysis, the similarity of the synergies to the master set was only 0.57 +/-
      0.54; however, the similarity improved to over 0.8 with more than ten muscles. We
      identified two methods, selecting dominant muscles from the master set or
      selecting muscles with the largest maximum isometric force, which significantly
      improved similarity to the master set and can help guide future experimental
      design. Analyses that included a small subset of muscles also over-estimated the
      variance accounted for (VAF) by the synergies compared to an analysis with all
      muscles. Thus, researchers should use caution using VAF to evaluate synergies
      when EMG is measured from a small subset of muscles. 

PMID- 23964233
TI  - Premotor cortex is critical for goal-directed actions.
AB  - Shifting between motor plans is often necessary for adaptive behavior. When faced
      with changing consequences of one's actions, it is often imperative to switch
      from automatic actions to deliberative and controlled actions. The pre
      supplementary motor area (pre-SMA) in primates, akin to the premotor cortex (M2)
      in mice, has been implicated in motor learning and planning, and action
      switching. We hypothesized that M2 would be differentially involved in goal
      directed actions, which are controlled by their consequences vs. habits, which
      are more dependent on their past reinforcement history and less on their
      consequences. To investigate this, we performed M2 lesions in mice and then
      concurrently trained them to press the same lever for the same food reward using
      two different schedules of reinforcement that differentially bias towards the use
      of goal-directed versus habitual action strategies. We then probed whether
      actions were dependent on their expected consequence through outcome revaluation
      testing. We uncovered that M2 lesions did not affect the acquisition of lever
      pressing. However, in mice with M2 lesions, lever-pressing was insensitive to
      changes in expected outcome value following goal-directed training. However,
      habitual actions were intact. We confirmed a role for M2 in goal-directed but not
      habitual actions in separate groups of mice trained on the individual schedules
      biasing towards goal-directed versus habitual actions. These data indicate that
      M2 is critical for actions to be updated based on their consequences, and suggest
      that habitual action strategies may not require processing by M2 and the updating
      of motor plans. 

PMID- 23964234
TI  - Fully automated rodent brain MR image processing pipeline on a Midas server: from
      acquired images to region-based statistics.
AB  - Magnetic resonance imaging (MRI) of rodent brains enables study of the
      development and the integrity of the brain under certain conditions (alcohol,
      drugs etc.). However, these images are difficult to analyze for biomedical
      researchers with limited image processing experience. In this paper we present an
      image processing pipeline running on a Midas server, a web-based data storage
      system. It is composed of the following steps: rigid registration, skull
      stripping, average computation, average parcellation, parcellation propagation to
      individual subjects, and computation of region-based statistics on each image.
      The pipeline is easy to configure and requires very little image processing
      knowledge. We present results obtained by processing a data set using this
      pipeline and demonstrate how this pipeline can be used to find differences
      between populations. 

PMID- 23964235
TI  - Natural selection of mitochondria during somatic lifetime promotes healthy aging.
AB  - Stimulation of mitochondrial biogenesis during life-time challenges both
      eliminates disadvantageous properties and drives adaptive selection of
      advantageous phenotypic variations. Intermittent fission and fusion of
      mitochondria provide specific targets for health promotion by brief temporal
      stressors, interspersed with periods of recovery and biogenesis. For
      mitochondria, the mechanisms of selection, variability, and heritability, are
      complicated by interaction of two independent genomes, including the multiple
      copies of DNA in each mitochondrion, as well as the shared nuclear genome of each
      cell. The mechanisms of stress-induced fission, followed by recovery-induced
      fusion and biogenesis, drive the improvement of mitochondrial functions, not only
      as directed by genotypic variations, but also as enabled by phenotypic diversity.
      Selective adaptation may explain unresolved aspects of aging, including the
      health effects of exercise, hypoxic and poisonous preconditioning, and tissue
      specific mitochondrial differences. We propose that intermittent purposeful
      enhancement of mitochondrial biogenesis by stressful episodes with subsequent
      recovery paradoxically promotes adaptive mitochondrial health and continued
      healthy aging. 

PMID- 23964236
TI  - Leptin regulation of neuronal morphology and hippocampal synaptic function.
AB  - The central actions of the hormone leptin in regulating energy homeostasis via
      the hypothalamus are well documented. However, evidence is growing that this
      hormone can also modify the structure and function of synapses throughout the
      CNS. The hippocampus is a region of the forebrain that plays a crucial role in
      associative learning and memory and is an area also highly vulnerable to
      neurodegenerative processes. Recent studies indicate that leptin is a potential
      cognitive enhancer as it modulates the cellular processes underlying hippocampal
      dependent learning and memory including dendritic morphology, glutamate receptor
      trafficking and activity-dependent synaptic plasticity. Here, we review the
      recent evidence implicating the hormone leptin as a key regulator of hippocampal
      synaptic function and discuss the role of leptin receptor-driven lipid signaling
      pathways involved in this process. 

PMID- 23964237
TI  - Lessons from two prevalent amyloidoses-what amylin and Abeta have in common.
AB  - The amyloidogenic peptide Abeta plays a key role in Alzheimer's disease (AD)
      forming insoluble aggregates in the brain. The peptide shares its amyloidogenic
      properties with amylin that forms aggregates in the pancreas of patients with
      Type 2 Diabetes mellitus (T2DM). While epidemiological studies establish a link
      between these two diseases, it is becoming increasingly clear that they also
      share biochemical features suggesting common pathogenic mechanisms. We discuss
      commonalities as to how Abeta and amylin deregulate the cellular proteome, how
      they impair mitochondrial functions, to which receptors they bind, aspects of
      their clearance and how therapeutic strategies exploit the commonalities between
      Abeta and amylin. We conclude that research into these two molecules is mutually
      beneficial for the treatment of AD and T2DM. 

PMID- 23964238
TI  - Evidence for loss of synaptic AMPA receptors in anterior piriform cortex of aged
      mice.
AB  - It has been suggested that age-related impairments in learning and memory may be
      due to age-related deficits in long-term potentiation of glutamatergic synaptic
      transmission. For example, olfactory discrimination learning is significantly
      affected by aging in mice and this may be due, in part, to diminished synaptic
      plasticity in piriform cortex. In the present study, we tested for alterations in
      electrophysiological properties and synaptic transmission in this simple cortical
      network. Whole-cell recordings were made from principal neurons in slices of
      anterior piriform cortex from young (3-6 months old) and old (24-28 months)
      C57Bl/6 mice. Miniature excitatory postsynaptic currents (mEPSCs) mediated by
      AMPA receptors were collected from cells in presence of tetrodotoxin (TTX) and
      held at -80 mV in voltage-clamp. Amplitudes of mEPSCs were significantly reduced
      in aged mice, suggesting that synaptic AMPA receptor expression is decreased
      during aging. In a second set of experiments, spontaneous excitatory postsynaptic
      currents (s/mEPSCs) were recorded in slices from different cohorts of young and
      old mice, in the absence of TTX. These currents resembled mEPSCs and were
      similarly reduced in amplitude in old mice. The results represent the first
      electrophysiological evidence for age-related declines in glutamatergic synaptic
      function in the mammalian olfactory system. 

PMID- 23964239
TI  - Exposure to chronic mild stress prevents kappa opioid-mediated reinstatement of
      cocaine and nicotine place preference.
AB  - Stress increases the risk of drug abuse, causes relapse to drug seeking, and
      potentiates the rewarding properties of both nicotine and cocaine. Understanding
      the mechanisms by which stress regulates the rewarding properties of drugs of
      abuse provides valuable insight into potential treatments for drug abuse. Prior
      reports have demonstrated that stress causes dynorphin release, activating kappa
      opioid receptors (KOR) in monoamine circuits resulting in both potentiation and
      reinstatement of cocaine and nicotine conditioned place preference. Here we
      report that kappa opioid-dependent reinstatement of cocaine and nicotine place
      preference is reduced when the mice are exposed to a randomized chronic mild
      stress (CMS) regime prior to training in a conditioned place preference
      reinstatement paradigm. The CMS schedule involves seven different stressors
      (removal of nesting for 24 h, 5 min forced swim stress at 15 degrees C, 8 h food
      and water deprivation, damp bedding overnight, white noise, cage tilt, and
      disrupted home cage lighting) rotated over a 3-week period. This response is KOR
      selective, as CMS does not protect against cocaine or nicotine drug-primed
      reinstatement. This protection from reinstatement is also observed following sub
      chronic social defeat stress, where each mouse is placed in an aggressor mouse
      home cage for a period of 20 min over 5 days. In contrast, a single acute
      stressor resulted in a potentiation of KOR-induced reinstatement, as previously
      reported. Prior studies have shown that stress alters sensitivity to opioids and
      prior stress can influence the pharmacodynamics of the opioid receptor system.
      Together, these findings suggest that exposure to different forms of stress may
      cause a dysregulation of kappa opioid circuitry and that changes resulting from
      mild stress can have protective and adaptive effects against drug relapse. 

PMID- 23964241
TI  - Drosophila melanogaster larvae control amylase secretion according to the
      hardness of food.
AB  - Drosophila melanogaster larvae excrete amylase and perform external digestion of
      their food. In this study, to investigate whether their external digestion
      ability varies in response to changes in the external environment, we measured
      the relative amount of amylase excreted by larvae using a new method: the iodine
      starch agar method (ISAM). Analysis using this method revealed that the amount of
      amylase excreted by larvae increased in accordance with the increase in the agar
      concentration. In addition, we investigated the effect on the larval growth rate
      of adding amylase to the diet. Pupation occurred 24 h later in food containing 1%
      amylase than in food containing no amylase. These results suggest that the larvae
      adjust their amylase excretion in response to changes in the external
      environment, and that its level has a marked influence on the larval growth rate.

PMID- 23964240
TI  - Antidepressant activity: contribution of brain microdialysis in knock-out mice to
      the understanding of BDNF/5-HT transporter/5-HT autoreceptor interactions.
AB  - Why antidepressants vary in terms of efficacy is currently unclear. Despite the
      leadership of selective serotonin reuptake inhibitors (SSRIs) in the treatment of
      depression, the precise neurobiological mechanisms involved in their therapeutic
      action are poorly understood. A better knowledge of molecular interactions
      between monoaminergic system, pre- and post-synaptic partners, brain neuronal
      circuits and regions involved may help to overcome limitations of current
      treatments and identify new therapeutic targets. Intracerebral in vivo
      microdialysis (ICM) already provided important information about the brain
      mechanism of action of antidepressants first in anesthetized rats in the early
      1990s, and since then in conscious wild-type or knock-out mice. The principle of
      ICM is based on the balance between release of neurotransmitters (e.g.,
      monoamines) and reuptake by selective transporters [e.g., serotonin transporter
      for serotonin 5-hydroxytryptamine (5-HT)]. Complementary to electrophysiology,
      this technique reflects pre-synaptic monoamines release and intrasynaptic events
      corresponding to ~80% of whole brain tissue content. The inhibitory role of
      serotonergic autoreceptors infers that they limit somatodendritic and nerve
      terminal 5-HT release. It has been proposed that activation of 5-HT1A and 5-HT1B
      receptor sub-types limits the antidepressant-like activity of SSRIs. This
      hypothesis is based partially on results obtained in ICM experiments performed in
      naive, non-stressed rodents. The present review will first remind the principle
      and methodology of ICM performed in mice. The crucial need of developing animal
      models that display anxiety and depression-like behaviors, neurochemical and
      brain morphological phenotypes reminiscent of these mood disorders in humans,
      will be underlined. Recently developed genetic mouse models have been generated
      to independently manipulate 5-HT1A auto and heteroreceptors and ICM helped to
      clarify the role of the pre-synaptic component, i.e., by measuring extracellular
      levels of neurotransmitters in serotonergic nerve terminal regions and raphe
      nuclei. Finally, we will summarize main advantages of using ICM in mice through
      recent examples obtained in knock-outs (drug infusion through the ICM probe
      allows the search of a correlation between changes in extracellular
      neurotransmitter levels and antidepressant-like activity) or alternatives
      (infusion of a small-interfering RNA suppressing receptor functions in the mouse
      brain). We will also focus this review on post-synaptic components such as brain
      derived neurotrophic factor in adult hippocampus that plays a crucial role in the
      neurogenic and anxiolytic/antidepressant-like activity of chronic SSRI treatment.
      Limitations of ICM will also be considered. 

PMID- 23964242
TI  - Longitudinal changes in intracardiac repolarization lability in patients with
      implantable cardioverter-defibrillator.
AB  - BACKGROUND: While it is known that elevated baseline intracardiac repolarization
      lability is associated with the risk of fast ventricular tachycardia
      (FVT)/ventricular fibrillation (VF), the effect of its longitudinal changes on
      the risk of FVT/VF is unknown. METHODS AND RESULTS: Near-field (NF) right
      ventricular (RV) intracardiac electrograms (EGMs) were recorded every 3-6 months
      at rest in 248 patients with structural heart disease [mean age 61.2 +/- 13.3;
      185(75%) male; 162(65.3%) ischemic cardiomyopathy] and implanted cardioverter
      defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D)
      [201 (81%) primary prevention]. Intracardiac beat-to-beat QT variability index
      (QTVINF) was measured on NF RV EGM. During the first study phase (median 18
      months), participants made on average 2.4 visits. Then remote follow-up was
      continued for an additional median period of 3 years. Average QTVINF did not
      change during the first year after ICD implantation (-0.342 +/- 0.603 at baseline
      vs. -0.262 +/- 0.552 at 6 months vs. -0.334 +/- 0.603 at 12 months); however, it
      decreased thereafter (-0.510 +/- 0.603 at 18 months; P = 0.042). Adjusted
      population-averaged GEE model showed that the odds of developing FVT/VF increased
      by 75% for each 1 unit increase in QTVINF. (OR 1.75 [95%CI 1.05-2.92]; P =
      0.031). However, individual patient-specific QTVINF trends (increasing,
      decreasing, flat) varied from patient to patient. For a given patient, the odds
      of developing FVT/VF were not associated with increasing or decreasing QTVINF
      over time [OR 1.27; (95%CI 0.05-30.10); P = 0.881]. CONCLUSION: While on average
      the odds of FVT/VF increased with an increase in QTVINF, patient-specific
      longitudinal trends in QTVINF did not affect the odds of FVT/VF.

PMID- 23964243
TI  - Physical activity ameliorates cardiovascular health in elderly subjects: the
      functional role of the beta adrenergic system.
AB  - Aging is a complex process characterized by a gradual decline in organ functional
      reserves, which eventually reduces the ability to maintain homeostasis. An
      exquisite feature of elderly subjects, which constitute a growing proportion of
      the world population, is the high prevalence of cardiovascular disorders, which
      negatively affect both the quality of life and the life expectancy. It is widely
      acknowledged that physical activity represents one of the foremost interventions
      capable in reducing the health burden of cardiovascular disease. Interestingly,
      the benefits of moderate-intensity physical activity have been established both
      in young and elderly subjects. Herein we provide a systematic and updated
      appraisal of the literature exploring the pathophysiological mechanisms evoked by
      physical activity in the elderly, focusing on the functional role of the beta
      adrenergic system. 

PMID- 23964244
TI  - Using complexity metrics with R-R intervals and BPM heart rate measures.
AB  - Lately, growing attention in the health sciences has been paid to the dynamics of
      heart rate as indicator of impending failures and for prognoses. Likewise, in
      social and cognitive sciences, heart rate is increasingly employed as a measure
      of arousal, emotional engagement and as a marker of interpersonal coordination.
      However, there is no consensus about which measurements and analytical tools are
      most appropriate in mapping the temporal dynamics of heart rate and quite
      different metrics are reported in the literature. As complexity metrics of heart
      rate variability depend critically on variability of the data, different choices
      regarding the kind of measures can have a substantial impact on the results. In
      this article we compare linear and non-linear statistics on two prominent types
      of heart beat data, beat-to-beat intervals (R-R interval) and beats-per-min
      (BPM). As a proof-of-concept, we employ a simple rest-exercise-rest task and show
      that non-linear statistics-fractal (DFA) and recurrence (RQA) analyses-reveal
      information about heart beat activity above and beyond the simple level of heart
      rate. Non-linear statistics unveil sustained post-exercise effects on heart rate
      dynamics, but their power to do so critically depends on the type data that is
      employed: While R-R intervals are very susceptible to non-linear analyses, the
      success of non-linear methods for BPM data critically depends on their
      construction. Generally, "oversampled" BPM time-series can be recommended as they
      retain most of the information about non-linear aspects of heart beat dynamics. 

PMID- 23964245
TI  - Enlarged thalamic volumes and increased fractional anisotropy in the thalamic
      radiations in veterans with suicide behaviors.
AB  - Post-mortem studies have suggested a link between the thalamus, psychiatric
      disorders, and suicide. We evaluated the thalamus and anterior thalamic
      radiations (ATR) in a group of Veterans with and without a history of suicidal
      behavior (SB) to determine if thalamic abnormalities were associated with an
      increased risk of SB. Forty Veterans with mild traumatic brain injury (TBI) and
      no SB (TBI-SB), 19 Veterans with mild TBI and a history of SB (TB + SB), and 15
      healthy controls (HC) underwent magnetic resonance imaging scanning including a
      structural and diffusion tensor imaging scan. SBs were evaluated utilizing the
      Columbia Suicide Rating Scale and impulsivity was measured using the Barratt
      Impulsiveness Scale (BIS). Differences in thalamic volumes and ATR fractional
      anisotropy (FA) were examined between (1) TBI + SB versus HC and (2) TBI + SB
      versus combined HC and TBI-SB and (3) between TBI + SB and TBI-SB. Left and right
      thalamic volumes were significantly increased in those with TBI + SB compared to
      the HC, TBI-SB, and the combined group. Veterans with TBI + SB had increased FA
      bilaterally compared to the HC, HC and TBI-SB group, and the TBI-SB only group.
      Significant positive associations were found for bilateral ATR and BIS in the TBI
      + SB group. Our findings of thalamic enlargement and increased FA in individuals
      with TBI + SB suggest that this region may be a biomarker for suicide risk. Our
      findings are consistent with previous evidence indicating that suicide may be
      associated with behavioral disinhibition and frontal-thalamic-limbic dysfunction
      and suggest a neurobiologic mechanism that may increase vulnerability to suicide.

PMID- 23964246
TI  - Performance in neurocognitive tasks in obese patients. Does somatic comorbidity
      matter?
AB  - The aim of the present study was to examine if obese individuals with obesity
      related somatic comorbidity (i.e., hypertension, diabetes, sleep apnea,
      dyslipidemia, pain disorder) perform worse in neurocognitive tasks compared to
      obese individuals without any somatic disorder. Neurocognitive functioning was
      measured by a computerized test battery that consisted of the following tasks:
      Corsi Block Tapping Test, Auditory Word Learning Task, Trail Making Test-Part B,
      Stroop Test, Labyrinth Test, and a four-disk version of the Tower of Hanoi. The
      total sample consisted of 146 patients, the majority (N = 113) suffered from
      obesity grade 3, 26 individuals had obesity grade 2, and only 7 individuals
      obesity grade 1. Ninety-eight participants (67.1%) reported at least one somatic
      disorder (Soma(+)-group). Hypertension was present in 75 individuals (51.4%),
      type 2 diabetes in 34 participants (23.3%), 38 individuals had sleep apnea
      (26.0%), 16 suffered from dyslipidemia (11.0%), and 14 individuals reported
      having a chronic pain disorder (9.6%). Participants without a coexisting somatic
      disorder were younger [M Soma- = 33.7, SD = 9.8 vs. M Soma+ = 42.7, SD = 11.0,
      F(1, 144) = 23.01, p < 0.001] and more often female [89.6 and 62.2%, chi(2)(1) =
      11.751, p = 0.001] but did not differ with respect to education, regular binge
      eating, or depressive symptoms from those in the Soma(+)-group. The Soma(-)-group
      performed better on cognitive tasks related to memory and mental flexibility.
      However, the group differences disappeared completely after controlling for age.
      The findings indicate that in some obese patients increasing age may not only be
      accompanied by an increase of obesity severity and by more obesity-related
      somatic disorders but also by poorer cognitive functioning. 

PMID- 23964247
TI  - Bacchus by Caravaggio as the Visual Diagnosis of Alcohol Use Disorder from the
      Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM
      5).

PMID- 23964248
TI  - Cognitive impairment in bipolar disorder and schizophrenia: a systematic review.
AB  - AIMS: Previous comparisons of cognitive decline among patients with bipolar
      disorder (BD) and schizophrenia (SZ) have found somehow quite similar profiles of
      deficits, but results have varied between studies. Therefore an extensive and
      thoughtful systematic review of the matter is warranted. METHODS: Studies were
      found through systematic search (PubMed) following PRISMA guidelines. To be
      included, studies must have assessed the following cognitive functions: executive
      functions, memory, IQ, attention-concentration, and perceptuomotor function. In
      order to make comparison between the two entities, studies should include BD
      patients with operationally defined euthymia, schizophrenic patients in
      remission, and third group of healthy control patients. Comparisons were made
      after controlling for years of schooling and residual affective symptoms.
      RESULTS: We found that overall both SZ and BD patients present deficits on all
      neurocognitive measures compared to healthy controls. In particular, SZ patients
      show more severe and pervasive cognitive deficits while BD patients present a
      milder and more confined impairment. In addition, evidence from the literature
      suggests that SZ and BD patients share a similar cognitive impairment profile
      with different degrees of deficits. Therefore, the difference between the two
      groups seems to be more quantitative (degree of deficit) rather than qualitative
      (profile), supporting a dimensional approach to the two clinical entities.
      Limitations of the present review includes the impossibility to control for
      effects of medication, varying time required for assessment across studies,
      illness diagnosis reliability, and course severity. CONCLUSION: Patients with BD
      might exhibit a cognitive impairment that could be similar to SZ in terms of
      their profile, although patients with SZ may have more severe and widespread
      impairments.

PMID- 23964250
TI  - Predicting musically induced emotions from physiological inputs: linear and
      neural network models.
AB  - Listening to music often leads to physiological responses. Do these physiological
      responses contain sufficient information to infer emotion induced in the
      listener? The current study explores this question by attempting to predict
      judgments of "felt" emotion from physiological responses alone using linear and
      neural network models. We measured five channels of peripheral physiology from 20
      participants-heart rate (HR), respiration, galvanic skin response, and activity
      in corrugator supercilii and zygomaticus major facial muscles. Using valence and
      arousal (VA) dimensions, participants rated their felt emotion after listening to
      each of 12 classical music excerpts. After extracting features from the five
      channels, we examined their correlation with VA ratings, and then performed
      multiple linear regression to see if a linear relationship between the
      physiological responses could account for the ratings. Although linear models
      predicted a significant amount of variance in arousal ratings, they were unable
      to do so with valence ratings. We then used a neural network to provide a non
      linear account of the ratings. The network was trained on the mean ratings of
      eight of the 12 excerpts and tested on the remainder. Performance of the neural
      network confirms that physiological responses alone can be used to predict
      musically induced emotion. The non-linear model derived from the neural network
      was more accurate than linear models derived from multiple linear regression,
      particularly along the valence dimension. A secondary analysis allowed us to
      quantify the relative contributions of inputs to the non-linear model. The study
      represents a novel approach to understanding the complex relationship between
      physiological responses and musically induced emotion. 

PMID- 23964249
TI  - From resilience to vulnerability: mechanistic insights into the effects of stress
      on transitions in critical period plasticity.
AB  - While early experiences are proposed to be important for the emergence of anxiety
      and other mental health problems, there is little empirical research examining
      the impact of such experiences on the development of emotional learning. Of the
      research that has been performed in this area, however, a complex picture has
      emerged in which the maturation of emotion circuits is influenced by the early
      experiences of the animal. For example, under typical laboratory rearing
      conditions infant rats rapidly forget learned fear associations (infantile
      amnesia) and express a form of extinction learning which is relapse-resistant
      (i.e., extinction in infant rats may be due to fear erasure). In contrast, adult
      rats exhibit very long-lasting memories of past learned fear associations, and
      express a form of extinction learning that is relapse-prone (i.e., the fear
      returns in a number of situations). However, when rats are reared under stressful
      conditions then they exhibit adult-like fear retention and extinction behaviors
      at an earlier stage of development (i.e., good retention of learned fear and
      relapse-prone extinction learning). In other words, under typical rearing
      conditions infant rats appear to be protected from exhibiting anxiety whereas
      after adverse rearing fear learning appears to make those infants more vulnerable
      to the later development of anxiety. While the effects of different experiences
      on infant rats' fear retention and extinction are becoming better documented, the
      mechanisms which mediate the early transition seen following stress remain
      unclear. Here we suggest that rearing stress may lead to an early maturation of
      the molecular and cellular signals shown to be involved in the closure of
      critical period plasticity in sensory modalities (e.g., maturation of GABAergic
      neurons, development of perineuronal nets), and speculate that these signals
      could be manipulated in adulthood to reopen infant forms of emotional learning
      (i.e., those that favor resilience). 

PMID- 23964251
TI  - fMRI orientation decoding in V1 does not require global maps or globally coherent
      orientation stimuli.
AB  - The orientation of a large grating can be decoded from V1 functional magnetic
      resonance imaging (fMRI) data, even at low resolution (3-mm isotropic voxels).
      This finding has suggested that columnar-level neuronal information might be
      accessible to fMRI at 3T. However, orientation decodability might alternatively
      arise from global orientation-preference maps. Such global maps across V1 could
      result from bottom-up processing, if the preferences of V1 neurons were biased
      toward particular orientations (e.g., radial from fixation, or cardinal, i.e.,
      vertical or horizontal). Global maps could also arise from local recurrent or top
      down processing, reflecting pre-attentive perceptual grouping, attention
      spreading, or predictive coding of global form. Here we investigate whether fMRI
      orientation decoding with 2-mm voxels requires (a) globally coherent orientation
      stimuli and/or (b) global-scale patterns of V1 activity. We used opposite
      orientation gratings (balanced about the cardinal orientations) and spirals
      (balanced about the radial orientation), along with novel patch-swapped variants
      of these stimuli. The two stimuli of a patch-swapped pair have opposite
      orientations everywhere (like their globally coherent parent stimuli). However,
      the two stimuli appear globally similar, a patchwork of opposite orientations. We
      find that all stimulus pairs are robustly decodable, demonstrating that fMRI
      orientation decoding does not require globally coherent orientation stimuli.
      Furthermore, decoding remained robust after spatial high-pass filtering for all
      stimuli, showing that fine-grained components of the fMRI patterns reflect visual
      orientations. Consistent with previous studies, we found evidence for global
      radial and vertical preference maps in V1. However, these were weak or absent for
      patch-swapped stimuli, suggesting that global preference maps depend on globally
      coherent orientations and might arise through recurrent or top-down processes
      related to the perception of global form. 

PMID- 23964252
TI  - The role of consciousness in the phonological loop: hidden in plain sight.
AB  - We know from everyday experience that when we need to keep a small amount of
      verbal information "in mind" for a short period, an effective cognitive strategy
      is to silently rehearse the words. This basic cognitive strategy has been
      elegantly codified in Baddeley and colleagues model of verbal working memory, the
      phonological loop. Here we explore how the intuitive appeal of the phonological
      loop is grounded in the phenomenological experience of subvocal rehearsal as
      consisting of an interaction between an "inner voice" and an "inner ear." We
      focus particularly on how our intuitions about the phenomenological experience of
      "inner speech" might constrain or otherwise inform the functional architecture of
      information processing models of verbal working memory such as the phonological
      loop; and how, indeed, how ideas about consciousness may offer alternative
      explanations for the dual nature of inner speech in verbal working memory. 

PMID- 23964253
TI  - Contribution of coherent motion to the perception of biological motion among
      persons with Schizophrenia.
AB  - People with schizophrenia (SCZ) are impaired in several domains of visual
      processing, including the discrimination and detection of biological motion.
      However, the mechanisms underlying SCZ-related biological motion processing
      deficits are unknown. Moreover, whether these impairments are specific to
      biological motion or represent a more widespread visual motion processing deficit
      is unclear. In the current study, three experiments were conducted to investigate
      the contribution of global coherent motion processing to biological motion
      perception among patients with SCZ. In Experiments 1 and 2, participants with SCZ
      (n = 33) and healthy controls (n = 33) were asked to discriminate the direction
      of motion from upright and inverted point-light walkers in the presence and
      absence of a noise mask. Additionally, participants discriminated the direction
      of non-biological global coherent motion. In Experiment 3, participants
      discriminated the direction of motion from upright scrambled walkers (which
      contained only local motion information) and upright random position walkers
      (which contained only global form information). Consistent with previous
      research, results from Experiment 1 and 2 showed that people with SCZ exhibited
      deficits in the direction discrimination of point-light walkers; however, this
      impairment was accounted for by decreased performance in the coherent motion
      control task. Furthermore, results from Experiment 3 demonstrated similar
      performance in the discrimination of scrambled and random position point-light
      walkers. 

PMID- 23964254
TI  - Changes in the representation of space and time while listening to music.
AB  - Music is known to alter people's ordinary experience of space and time. Not only
      does this challenge the concept of invariant space and time tacitly assumed in
      psychology but it may also help us understand how music works and how music can
      be understood as an embodied experience. Yet research about these alterations is
      in its infancy. This review is intended to delineate a future research agenda. We
      review experimental evidence and subjective reports of the influence of music on
      the representation of space and time and present prominent approaches to
      explaining these effects. We discuss the role of absorption and altered states of
      consciousness and their associated changes in attention and neurophysiological
      processes, as well as prominent models of human time processing and time
      experience. After integrating the reviewed research, we conclude that research on
      the influence of music on the representation of space and time is still quite
      inconclusive but that integrating the different approaches could lead to a better
      understanding of the observed effects. We also provide a working model that
      integrates a large part of the evidence and theories. Several suggestions for
      further research in both music psychology and cognitive psychology are outlined. 

PMID- 23964255
TI  - The "Musical Emotional Bursts": a validated set of musical affect bursts to
      investigate auditory affective processing.
AB  - The Musical Emotional Bursts (MEB) consist of 80 brief musical executions
      expressing basic emotional states (happiness, sadness and fear) and neutrality.
      These musical bursts were designed to be the musical analog of the Montreal
      Affective Voices (MAV)-a set of brief non-verbal affective vocalizations
      portraying different basic emotions. The MEB consist of short (mean duration: 1.6
      s) improvisations on a given emotion or of imitations of a given MAV stimulus,
      played on a violin (10 stimuli * 4 [3 emotions + neutral]), or a clarinet (10
      stimuli * 4 [3 emotions + neutral]). The MEB arguably represent a primitive form
      of music emotional expression, just like the MAV represent a primitive form of
      vocal, non-linguistic emotional expression. To create the MEB, stimuli were
      recorded from 10 violinists and 10 clarinetists, and then evaluated by 60
      participants. Participants evaluated 240 stimuli [30 stimuli * 4 (3 emotions +
      neutral) * 2 instruments] by performing either a forced-choice emotion
      categorization task, a valence rating task or an arousal rating task (20 subjects
      per task); 40 MAVs were also used in the same session with similar task
      instructions. Recognition accuracy of emotional categories expressed by the MEB
      (n:80) was lower than for the MAVs but still very high with an average percent
      correct recognition score of 80.4%. Highest recognition accuracies were obtained
      for happy clarinet (92.0%) and fearful or sad violin (88.0% each) MEB stimuli.
      The MEB can be used to compare the cerebral processing of emotional expressions
      in music and vocal communication, or used for testing affective perception in
      patients with communication problems. 

PMID- 23964257
TI  - The psychological functions of music listening.
AB  - Why do people listen to music? Over the past several decades, scholars have
      proposed numerous functions that listening to music might fulfill. However,
      different theoretical approaches, different methods, and different samples have
      left a heterogeneous picture regarding the number and nature of musical
      functions. Moreover, there remains no agreement about the underlying dimensions
      of these functions. Part one of the paper reviews the research contributions that
      have explicitly referred to musical functions. It is concluded that a
      comprehensive investigation addressing the basic dimensions underlying the
      plethora of functions of music listening is warranted. Part two of the paper
      presents an empirical investigation of hundreds of functions that could be
      extracted from the reviewed contributions. These functions were distilled to 129
      non-redundant functions that were then rated by 834 respondents. Principal
      component analysis suggested three distinct underlying dimensions: People listen
      to music to regulate arousal and mood, to achieve self-awareness, and as an
      expression of social relatedness. The first and second dimensions were judged to
      be much more important than the third-a result that contrasts with the idea that
      music has evolved primarily as a means for social cohesion and communication. The
      implications of these results are discussed in light of theories on the origin
      and the functionality of music listening and also for the application of musical
      stimuli in all areas of psychology and for research in music cognition. 

PMID- 23964256
TI  - Measuring acuity of the approximate number system reliably and validly: the
      evaluation of an adaptive test procedure.
AB  - Two studies investigated the reliability and predictive validity of commonly used
      measures and models of Approximate Number System acuity (ANS). Study 1
      investigated reliability by both an empirical approach and a simulation of
      maximum obtainable reliability under ideal conditions. Results showed that common
      measures of the Weber fraction (w) are reliable only when using a substantial
      number of trials, even under ideal conditions. Study 2 compared different
      purported measures of ANS acuity as for convergent and predictive validity in a
      within-subjects design and evaluated an adaptive test using the ZEST algorithm.
      Results showed that the adaptive measure can reduce the number of trials needed
      to reach acceptable reliability. Only direct tests with non-symbolic numerosity
      discriminations of stimuli presented simultaneously were related to arithmetic
      fluency. This correlation remained when controlling for general cognitive ability
      and perceptual speed. Further, the purported indirect measure of ANS acuity in
      terms of the Numeric Distance Effect (NDE) was not reliable and showed no sign of
      predictive validity. The non-symbolic NDE for reaction time was significantly
      related to direct w estimates in a direction contrary to the expected. Easier
      stimuli were found to be more reliable, but only harder (7:8 ratio) stimuli
      contributed to predictive validity. 

PMID- 23964258
TI  - Serial binary interval ratios improve rhythm reproduction.
AB  - Musical rhythm perception is a natural human ability that involves complex
      cognitive processes. Rhythm refers to the organization of events in time, and
      musical rhythms have an underlying hierarchical metrical structure. The metrical
      structure induces the feeling of a beat and the extent to which a rhythm induces
      the feeling of a beat is referred to as its metrical strength. Binary ratios are
      the most frequent interval ratio in musical rhythms. Rhythms with hierarchical
      binary ratios are better discriminated and reproduced than rhythms with
      hierarchical non-binary ratios. However, it remains unclear whether a superiority
      of serial binary over non-binary ratios in rhythm perception and reproduction
      exists. In addition, how different types of serial ratios influence the metrical
      strength of rhythms remains to be elucidated. The present study investigated
      serial binary vs. non-binary ratios in a reproduction task. Rhythms formed with
      exclusively binary (1:2:4:8), non-binary integer (1:3:5:6), and non-integer
      (1:2.3:5.3:6.4) ratios were examined within a constant meter. The results showed
      that the 1:2:4:8 rhythm type was more accurately reproduced than the 1:3:5:6 and
      1:2.3:5.3:6.4 rhythm types, and the 1:2.3:5.3:6.4 rhythm type was more accurately
      reproduced than the 1:3:5:6 rhythm type. Further analyses showed that
      reproduction performance was better predicted by the distribution pattern of
      event occurrences within an inter-beat interval, than by the coincidence of
      events with beats, or the magnitude and complexity of interval ratios. Whereas
      rhythm theories and empirical data emphasize the role of the coincidence of
      events with beats in determining metrical strength and predicting rhythm
      performance, the present results suggest that rhythm processing may be better
      understood when the distribution pattern of event occurrences is taken into
      account. These results provide new insights into the mechanisms underlining
      musical rhythm perception. 

PMID- 23964259
TI  - Simpson's paradox in psychological science: a practical guide.
AB  - The direction of an association at the population-level may be reversed within
      the subgroups comprising that population-a striking observation called Simpson's
      paradox. When facing this pattern, psychologists often view it as anomalous.
      Here, we argue that Simpson's paradox is more common than conventionally thought,
      and typically results in incorrect interpretations-potentially with harmful
      consequences. We support this claim by reviewing results from cognitive
      neuroscience, behavior genetics, clinical psychology, personality psychology,
      educational psychology, intelligence research, and simulation studies. We show
      that Simpson's paradox is most likely to occur when inferences are drawn across
      different levels of explanation (e.g., from populations to subgroups, or
      subgroups to individuals). We propose a set of statistical markers indicative of
      the paradox, and offer psychometric solutions for dealing with the paradox when
      encountered-including a toolbox in R for detecting Simpson's paradox. We show
      that explicit modeling of situations in which the paradox might occur not only
      prevents incorrect interpretations of data, but also results in a deeper
      understanding of what data tell us about the world. 

PMID- 23964260
TI  - What I make up when I wake up: anti-experience views and narrative fabrication of
      dreams.
AB  - I propose a narrative fabrication thesis of dream reports, according to which
      dream reports are often not accurate representations of experiences that occur
      during sleep. I begin with an overview of anti-experience theses of Norman
      Malcolm and Daniel Dennett who reject the received view of dreams, that dreams
      are experiences we have during sleep which are reported upon waking. Although
      rejection of the first claim of the received view, that dreams are experiences
      that occur during sleep, is implausible, I evaluate in more detail the second
      assumption of the received view, that dream reports are generally accurate. I
      then propose a "narrative fabrication" view of dreams as an alternative to the
      received view. Dream reports are often confabulated or fabricated because of poor
      memory, bizarre dream content, and cognitive deficits. It is well documented that
      narratives can be altered between initial rapid eye movement sleep awakenings and
      subsequent reports. I argue that we have reason to suspect that initial reports
      are prone to inaccuracy. Experiments demonstrate that subjects rationalize
      strange elements in narratives, leaving out supernatural or bizarre components
      when reporting waking memories of stories. Inaccuracies in dream reports are
      exacerbated by rapid memory loss and bizarre dream content. Waking memory is a
      process of reconstruction and blending of elements, but unlike waking memory, we
      cannot reality-test for dream memories. Dream experiences involve imaginative
      elements, and dream content cannot be verified with external evidence. Some
      dreams may involve wake-like higher cognitive functions, such as lucid dreams.
      Such dreams are more likely to elicit accurate reports than cognitively deficient
      dreams. However, dream reports are generally less accurate than waking reports. I
      then propose methods which could verify the narrative fabrication view, and argue
      that although the theory cannot be tested with current methods, new techniques
      and technologies may be able to do so in the future. 

PMID- 23964261
TI  - The autobiographical IAT: a review.
AB  - The autobiographical Implicit Association Test (aIAT; Sartori et al., 2008) is a
      variant of the Implicit Association Test (IAT; Greenwald et al., 1998) that is
      used to establish whether an autobiographical memory is encoded in the
      respondent's mind/brain. More specifically, with the aIAT, it is possible to
      evaluate which one of two autobiographical events is true. The method consists of
      a computerized categorization task. The aIAT includes stimuli belonging to four
      categories, two of them are logical categories and are represented by sentences
      that are always true (e.g., I am in front of a computer) or always false (e.g., I
      am climbing a mountain) for the respondent; two other categories are represented
      by alternative versions of an autobiographical event (e.g., I went to Paris for
      Christmas, or I went to New York for Christmas), only one of which is true. The
      true autobiographical event is identified because, in a combined block, it gives
      rise to faster reaction times when it shares the same motor response with true
      sentences. Here, we reviewed all the validation experiments and found more than
      90% accuracy in detecting the true memory. We show that agreement in identifying
      the true autobiographical memory of the same aIAT repeated twice is, on average,
      more than 90%, and we report a technique for estimating accuracy associated with
      a single classification based on the D-IAT value, which may be used in single
      subject's investigations. We show that the aIAT might be used to identify also
      true intentions and reasons and conclude with a series of guidelines for building
      an effective aIAT. 

PMID- 23964262
TI  - Conceptual and methodological concerns in the theory of perceptual load.
AB  - The present paper provides a short critical review of the theory of perceptual
      load. It closely examines the basic tenets and assumptions of the theory and
      identifies major conceptual and methodological problems that have been largely
      ignored in the literature. The discussion focuses on problems in the definition
      of the concept of perceptual load, on the circularity in the characterization and
      manipulation of perceptual load and the confusion between the concept of
      perceptual load and its operationalization. The paper also selectively reviews
      evidence supporting the theory as well as inconsistent evidence which proposed
      alternative dominant factors influencing the efficacy of attentional selection. 

PMID- 23964263
TI  - Combined endovascular and microsurgical management of complex cerebral aneurysms.
AB  - Cerebral aneurysms are associated with a 50% mortality rate after rupture and
      patients can suffer significant morbidity during subsequent treatment.
      Neurosurgical management of both ruptured and unruptured aneurysms has evolved
      over the years. The historical practice of using microsurgical clipping to treat
      aneurysms has benefited in the last two decades from tremendous improvement in
      endovascular technology. Microsurgery and endovascular therapies are often viewed
      as competing treatments but it is important to recognize their individual
      limitations. Some aneurysms are considered complex, due to several factors such
      as aneurysm anatomy and a patient's clinical condition. A complex aneurysm often
      cannot be completely excluded with a single approach and its successful treatment
      requires a combination of microsurgical and endovascular techniques. Planning
      such an approach relies on understanding aneurysm anatomy and thus should
      routinely include 3D angiographic imaging. In patients with ruptured aneurysms,
      endovascular coiling is a well-tolerated early treatment and residual aneurysms
      can be treated with intervals of definitive clipping. Microsurgical clipping also
      can be used to reconstruct the neck of a complex aneurysm, allowing successful
      placement of coils across a narrow neck. Endovascular techniques are assisted by
      balloons, which can be used in coiling and testing parent vessel occlusion before
      sacrifice. In some cases microsurgical bypasses can provide alternate flow for
      planned vessel sacrifice. We present current paradigms for combining endovascular
      and microsurgical approaches to treat complex aneurysms and share our experience
      in 67 such cases. A dual microsurgical-endovascular approach addresses the
      challenge of intracranial aneurysms. This combination can be performed safely and
      produces excellent rates of aneurysm obliteration. Hybrid angiographic operating
      room suites can foster seamless and efficient complementary application of these
      two modalities. 

PMID- 23964264
TI  - Musical hallucinations and forgotten tunes - case report and brief literature
      review.
AB  - Musical hallucinations represent a specific form of auditory hallucinations
      whereby patients experience formed music without an external source. We describe
      a 60-year-old woman with history of bilateral hearing impairment and tinnitus who
      experienced both recognizable and non-recognizable songs. Curiously, she was able
      to reproduce non-recognizable songs in a way that could be recognized by others.
      This phenomenon is in line with current understanding that musical hallucinations
      represent abnormal activity in the auditory associative cortices, raising
      intriguing questions regarding memory, forgetting, and access to lost memories. 

PMID- 23964265
TI  - West syndrome treatment: new roads for an old syndrome.

PMID- 23964266
TI  - Are tau aggregates toxic or protective in tauopathies?
AB  - Aggregation of highly phosphorylated tau into aggregated forms such as filaments
      and neurofibrillary tangles is one of the defining pathological hallmarks of
      Alzheimer's disease and other tauopathies. Hence therapeutic strategies have
      focused on inhibition of tau phosphorylation or disruption of aggregation.
      However, animal models imply that tau-mediated dysfunction and toxicity do not
      require aggregation but instead are caused by soluble hyper-phosphorylated tau.
      Over the years, our findings from a Drosophila model of tauopathy have reinforced
      this. We have shown that highly phosphorylated wild-type human tau causes
      behavioral deficits resulting from synaptic dysfunction, axonal transport
      disruption, and cytoskeletal destabilization in vivo. These deficits are evident
      in the absence of neuronal death or filament/tangle formation. Unsurprisingly,
      both pharmacological and genetic inhibition of GSK-3beta rescue these tau
      phenotypes. However, GSK-3beta inhibition also unexpectedly increases tau protein
      levels, and produces insoluble granular tau oligomers. As well as underlining the
      growing consensus that tau toxicity is mediated by a highly phosphorylated
      soluble tau species, our findings further show that not all insoluble tau
      aggregates are toxic. Some tau aggregates, in particular tau oligomers, are non
      toxic, and may even be protective against tau toxicity in vivo. This has serious
      implications for emerging therapeutic strategies to dissolve tau aggregates,
      which might be ineffective or even counter-productive. In light of this, it is
      imperative to identify the key toxic tau species and to understand how it
      mediates dysfunction and degeneration so that the effective disease-modifying
      therapies can be developed. 

PMID- 23964267
TI  - Periodic Limb Movements during Sleep: A New Sleep-Related Cardiovascular Risk
      Factor?
AB  - In recent years, a growing body of evidence suggests that periodic limb movements
      during sleep (PLMS) are associated with hypertension, cardiovascular, and
      cerebrovascular risk. However, several non-mutually exclusive mechanisms may
      determine a higher cardiovascular risk in patients with PLMS and the link between
      the two remains controversial. Prospective data are scant and the temporal
      relationship between PLMS and acute vascular events is difficult to ascertain
      because although PLMS may lead to acute vascular events such as stroke, stroke
      may also give rise to PLMS. This article describes the clinical and polygraphic
      features of PLMS and examines the literature evidence linking PLMS with an
      increased risk for the development and progression of cardiovascular diseases,
      discussing the possible pathways of this association. 

PMID- 23964268
TI  - Recent advances in obesity-induced inflammation and insulin resistance.
AB  - It has been demonstrated in rodents and humans that chronic inflammation
      characterized by macrophage infiltration occurs mainly in adipose tissue or liver
      during obesity, in which activation of immune cells is closely associated with
      insulin sensitivity. Macrophages can be classified as classically activated (M1)
      macrophages that support microbicidal activity or alternatively activated (M2)
      macrophages that support allergic and antiparasitic responses. In the context of
      insulin action, M2 macrophages sustain insulin sensitivity by secreting IL-4 and
      IL-10, while M1 macrophages induce insulin resistance through the secretion of
      proinflammatory cytokines, such as TNFalpha. Polarization of M1/M2 is controlled
      by various dynamic functions of other immune cells. It has been demonstrated
      that, in a lean state, TH2 cells, Treg cells, natural killer T cells, or
      eosinophils contribute to the M2 activation of macrophages by secreting IL-4 or
      IL-10. In contrast, obesity causes alteration of the constituent immune cells, in
      which TH1 cells, B cells, neutrophils, or mast cells induce M1 activation of
      macrophages by the elevated secretion of TNFalpha and IFNgamma. Increased
      secretion of TNFalpha and free fatty acids from hypertrophied adipocytes also
      contributes to the M1 activation of macrophages. Since obesity-induced insulin
      resistance is established by macrophage infiltration and the activation of immune
      cells inside tissues, identification of the factors that regulate accumulation
      and the intracellular signaling cascades that define polarization of M1/M2 would
      be indispensable. Regulation of these factors would lead to the pharmacological
      inhibition of obesity-induced insulin resistance. In this review, we introduce
      molecular mechanisms relevant to the pathophysiology and review the most recent
      studies of clinical applications targeting chronic inflammation. 

PMID- 23964269
TI  - The regulated secretory pathway and human disease: insights from gene variants
      and single nucleotide polymorphisms.
AB  - The regulated secretory pathway provides critical control of peptide, growth
      factor, and hormone release from neuroendocrine and endocrine cells, and neurons,
      maintaining physiological homeostasis. Propeptides and prohormones are packaged
      into dense core granules (DCGs), where they frequently undergo tissue-specific
      processing as the DCG matures. Proteins of the granin family are DCG components,
      and although their function is not fully understood, data suggest they are
      involved in DCG formation and regulated protein/peptide secretion, in addition to
      their role as precursors of bioactive peptides. Association of gene variation,
      including single nucleotide polymorphisms (SNPs), with neuropsychiatric,
      endocrine, and metabolic diseases, has implicated specific secreted proteins and
      peptides in disease pathogenesis. For example, a SNP at position 196 (G/A) of the
      human brain-derived neurotrophic factor gene dysregulates protein processing and
      secretion and leads to cognitive impairment. This suggests more generally that
      variants identified in genes encoding secreted growth factors, peptides,
      hormones, and proteins involved in DCG biogenesis, protein processing, and the
      secretory apparatus, could provide insight into the process of regulated
      secretion as well as disorders that result when it is impaired. 

PMID- 23964271
TI  - Wide distribution of autochthonous branched glycerol dialkyl glycerol tetraethers
      (bGDGTs) in U.S. Great Basin hot springs.
AB  - Branched glycerol dialkyl glycerol tetraethers (bGDGTs) are membrane-spanning
      lipids that likely stabilize membranes of some bacteria. Although bGDGTs have
      been reported previously in certain geothermal environments, it has been
      suggested that they may derive from surrounding soils since bGDGTs are known to
      be produced by soil bacteria. To test the hypothesis that bGDGTs can be produced
      by thermophiles in geothermal environments, we examined the distribution and
      abundance of bGDGTs, along with extensive geochemical data, in 40 sediment and
      mat samples collected from geothermal systems in the U.S. Great Basin
      (temperature: 31-95 degrees C; pH: 6.8-10.7). bGDGTs were found in 38 out of 40
      samples at concentrations up to 824 ng/g sample dry mass and comprised up to
      99.5% of total GDGTs (branched plus isoprenoidal). The wide distribution of
      bGDGTs in hot springs, strong correlation between core and polar lipid
      abundances, distinctness of bGDGT profiles compared to nearby soils, and higher
      concentration of bGDGTs in hot springs compared to nearby soils provided evidence
      of in situ production, particularly for the minimally methylated bGDGTs I, Ib,
      and Ic. Polar bGDGTs were found almost exclusively in samples <=70 degrees C and
      the absolute abundance of polar bGDGTs correlated negatively with properties of
      chemically reduced, high temperature spring sources (temperature, H2S/HS(-)) and
      positively with properties of oxygenated, low temperature sites (O2, NO(-) 3).
      Two-way cluster analysis and nonmetric multidimensional scaling based on relative
      abundance of polar bGDGTs supported these relationships and showed a negative
      relationship between the degree of methylation and temperature, suggesting a
      higher abundance for minimally methylated bGDGTs at high temperature. This study
      presents evidence of the widespread production of bGDGTs in mats and sediments of
      natural geothermal springs in the U.S. Great Basin, especially in oxygenated, low
      temperature sites (<=70 degrees C). 

PMID- 23964270
TI  - O-GlcNAcylation: A New Cancer Hallmark?
AB  - O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post
      translational modification consisting in the addition of a sugar moiety to
      serine/threonine residues of cytosolic or nuclear proteins. Catalyzed by O-GlcNAc
      transferase (OGT) and removed by O-GlcNAcase, this dynamic modification is
      dependent on environmental glucose concentration. O-GlcNAcylation regulates the
      activities of a wide panel of proteins involved in almost all aspects of cell
      biology. As a nutrient sensor, O-GlcNAcylation can relay the effects of excessive
      nutritional intake, an important cancer risk factor, on protein activities and
      cellular functions. Indeed, O-GlcNAcylation has been shown to play a significant
      role in cancer development through different mechanisms. O-GlcNAcylation and OGT
      levels are increased in different cancers (breast, prostate, colon...) and vary
      during cell cycle progression. Modulating their expression or activity can alter
      cancer cell proliferation and/or invasion. Interestingly, major oncogenic factors
      have been shown to be directly O-GlcNAcylated (p53, MYC, NFkappaB, beta
      catenin...). Furthermore, chromatin dynamics is modulated by O-GlcNAc. DNA
      methylation enzymes of the Tet family, involved epigenetic alterations associated
      with cancer, were recently found to interact with and target OGT to multi
      molecular chromatin-remodeling complexes. Consistently, histones are subjected to
      O-GlcNAc modifications which regulate their function. Increasing number of
      evidences point out the central involvement of O-GlcNAcylation in tumorigenesis,
      justifying the attention received as a potential new approach for cancer
      treatment. However, comprehension of the underlying mechanism remains at its
      beginnings. Future challenge will be to address directly the role of O-GlcNAc
      modified residues in oncogenic-related proteins to eventually propose novel
      strategies to alter cancer development and/or progression. 

PMID- 23964272
TI  - Dynamic relationships between microbial biomass, respiration, inorganic nutrients
      and enzyme activities: informing enzyme-based decomposition models.
AB  - We re-examined data from a recent litter decay study to determine if additional
      insights could be gained to inform decomposition modeling. Rinkes et al. (2013)
      conducted 14-day laboratory incubations of sugar maple (Acer saccharum) or white
      oak (Quercus alba) leaves, mixed with sand (0.4% organic C content) or loam (4.1%
      organic C). They measured microbial biomass C, carbon dioxide efflux, soil
      ammonium, nitrate, and phosphate concentrations, and beta-glucosidase (BG), beta
      N-acetyl-glucosaminidase (NAG), and acid phosphatase (AP) activities on days 1,
      3, and 14. Analyses of relationships among variables yielded different insights
      than original analyses of individual variables. For example, although respiration
      rates per g soil were higher for loam than sand, rates per g soil C were actually
      higher for sand than loam, and rates per g microbial C showed little difference
      between treatments. Microbial biomass C peaked on day 3 when biomass-specific
      activities of enzymes were lowest, suggesting uptake of litter C without
      extracellular hydrolysis. This result refuted a common model assumption that all
      enzyme production is constitutive and thus proportional to biomass, and/or
      indicated that part of litter decay is independent of enzyme activity. The length
      and angle of vectors defined by ratios of enzyme activities (BG/NAG vs. BG/AP)
      represent relative microbial investments in C (length), and N and P (angle)
      acquiring enzymes. Shorter lengths on day 3 suggested low C limitation, whereas
      greater lengths on day 14 suggested an increase in C limitation with decay. The
      soils and litter in this study generally had stronger P limitation (angles >45
      degrees ). Reductions in vector angles to <45 degrees  for sand by day 14
      suggested a shift to N limitation. These relational variables inform enzyme-based
      models, and are usually much less ambiguous when obtained from a single study in
      which measurements were made on the same samples than when extrapolated from
      separate studies. 

PMID- 23964274
TI  - CD8alphaalpha Expression Marks Terminally Differentiated Human CD8+ T Cells
      Expanded in Chronic Viral Infection.
AB  - The T cell co-receptor CD8alphabeta enhances T cell sensitivity to antigen,
      however studies indicate CD8alphaalpha has the converse effect and acts as a co
      repressor. Using a combination of Thymic Leukemia (TL) antigen tetramer, which
      directly binds CD8alphaalpha, anti-CD161, and anti-Valpha7.2 antibodies we have
      been able for the first time to clearly define CD8alphaalpha expression on human
      CD8 T cells subsets. In healthy controls CD8alphaalpha is most highly expressed
      by CD161 "bright" (CD161++) mucosal associated invariant T (MAIT) cells, with
      CD8alphaalpha expression highly restricted to the TCR Valpha7.2+ cells of this
      subset. We also identified CD8alphaalpha-expressing populations within the CD161
      "mid" (CD161+) and "negative" (CD161-) non-MAIT CD8 T cell subsets and show TL
      tetramer binding to correlate with expression of CD8beta at low levels in the
      context of maintained CD8alpha expression (CD8alpha+CD8beta(low)). In addition,
      we found CD161-CD8alpha+CD8beta(low) populations to be significantly expanded in
      the peripheral blood of HIV-1 and hepatitis B (mean of 47 and 40% of CD161- T
      cells respectively) infected individuals. Such CD8alphaalpha expressing T cells
      are an effector-memory population (CD45RA-, CCR7-, CD62L-) that express markers
      of activation and maturation (HLA-DR+, CD28-, CD27-, CD57+) and are functionally
      distinct, expressing greater levels of TNF-alpha and IFN-gamma on stimulation and
      perforin at rest than their CD8alpha+CD8beta(high) counterparts. Antigen-specific
      T cells in HLA-B(*)4201+HIV-1 infected patients are found within both the CD161
      CD8alpha+CD8beta(high) and CD161-CD8alpha+CD8beta(low) populations. Overall we
      have clearly defined CD8alphaalpha expressing human T cell subsets using the TL
      tetramer, and have demonstrated CD161-CD8alpha+CD8beta(low) populations, highly
      expanded in disease settings, to co-express CD8alphabeta and CD8alphaalpha. Co
      expression of CD8alphaalpha on CD8alphabeta T cells may impact on their overall
      function in vivo and contribute to the distinctive phenotype of highly
      differentiated populations in HBV and HIV-1 infection. 

PMID- 23964273
TI  - Secretory IgA: Designed for Anti-Microbial Defense.
AB  - Prevention of infections by vaccination remains a compelling goal to improve
      public health. Mucosal vaccines would make immunization procedures easier, be
      better suited for mass administration, and most efficiently induce immune
      exclusion - a term coined for non-inflammatory antibody shielding of internal
      body surfaces, mediated principally by secretory immunoglobulin A (SIgA). The
      exported antibodies are polymeric, mainly IgA dimers (pIgA), produced by local
      plasma cells (PCs) stimulated by antigens that target the mucose. SIgA was early
      shown to be complexed with an epithelial glycoprotein - the secretory component
      (SC). A common SC-dependent transport mechanism for pIgA and pentameric IgM was
      then proposed, implying that membrane SC acts as a receptor, now usually called
      the polymeric Ig receptor (pIgR). From the basolateral surface, pIg-pIgR
      complexes are taken up by endocytosis and then extruded into the lumen after
      apical cleavage of the receptor - bound SC having stabilizing and innate
      functions in the secretory antibodies. Mice deficient for pIgR show that this is
      the only receptor responsible for epithelial export of IgA and IgM. These
      knockout mice show a variety of defects in their mucosal defense and changes in
      their intestinal microbiota. In the gut, induction of B-cells occurs in gut
      associated lymphoid tissue, particularly the Peyer's patches and isolated
      lymphoid follicles, but also in mesenteric lymph nodes. PC differentiation is
      accomplished in the lamina propria to which the activated memory/effector B-cells
      home. The airways also receive such cells from nasopharynx-associated lymphoid
      tissue but by different homing receptors. This compartmentalization is a
      challenge for mucosal vaccination, as are the mechanisms used by the mucosal
      immune system to discriminate between commensal symbionts (mutualism),
      pathobionts, and overt pathogens (elimination). 

PMID- 23964275
TI  - Antigen and transforming growth factor Beta receptors contribute to long term
      functional and phenotypic heterogeneity of memory CD8 T cells.
AB  - Pathogen-specific CD8 T cells provide a mechanism for selectively eliminating
      host cells that are harboring intracellular pathogens. The pathogens are killed
      when lytic molecules are injected into the cytoplasm of the infected cells and
      begin an apoptotic cascade. Activated CD8 T cells also release large quantities
      of pro-inflammatory cytokines that stimulate other immune cells in the local
      vicinity. As the alveoli are extraordinarily sensitive to cytokine induced
      damage, multiple layers of immune regulation limit the activities of immune cells
      that enter the lungs. These mechanisms include receptor-mediated signaling
      pathways in CD8 T cells that respond to peptide antigens and transforming growth
      factor beta. Both pathways influence the functional and phenotypic properties of
      long-lived CD8 T cells populations in peripheral and lymphoid tissues. 

PMID- 23964276
TI  - Binding of Soluble Yeast beta-Glucan to Human Neutrophils and Monocytes is
      Complement-Dependent.
AB  - The immunomodulatory properties of yeast beta-1,3/1,6 glucans are mediated
      through their ability to be recognized by human innate immune cells. While
      several studies have investigated binding of opsonized and unopsonized
      particulate beta-glucans to human immune cells mainly via complement receptor 3
      (CR3) or Dectin-1, few have focused on understanding the binding characteristics
      of soluble beta-glucans. Using a well-characterized, pharmaceutical-grade,
      soluble yeast beta-glucan, this study evaluated and characterized the binding of
      soluble beta-glucan to human neutrophils and monocytes. The results demonstrated
      that soluble beta-glucan bound to both human neutrophils and monocytes in a
      concentration-dependent and receptor-specific manner. Antibodies blocking the
      CD11b and CD18 chains of CR3 significantly inhibited binding to both cell types,
      establishing CR3 as the key receptor recognizing the soluble beta-glucan in these
      cells. Binding of soluble beta-glucan to human neutrophils and monocytes required
      serum and was also dependent on incubation time and temperature, strongly
      suggesting that binding was complement-mediated. Indeed, binding was reduced in
      heat-inactivated serum, or in serum treated with methylamine or in serum reacted
      with the C3-specific inhibitor compstatin. Opsonization of soluble beta-glucan
      was demonstrated by detection of iC3b, the complement opsonin on beta-glucan
      bound cells, as well as by the direct binding of iC3b to beta-glucan in the
      absence of cells. Binding of beta-glucan to cells was partially inhibited by
      blockade of the alternative pathway of complement, suggesting that the C3
      activation amplification step mediated by this pathway also contributed to
      binding. 

PMID- 23964277
TI  - The impact of aging on regulatory T-cells.
AB  - Age-related deviations of the immune system contribute to a higher likelihood of
      infections, cancer, and autoimmunity in the elderly. Senescence of T-lymphocytes
      is characterized by phenotypical and functional changes including the loss of
      characteristic T-cell surface markers, while an increase of stimulatory
      receptors, cytotoxicity as well as resistance against apoptosis is observed. One
      of the key mediators of immune regulation are naturally occurring regulatory T
      cells (Tregs). Tregs express high levels of CD25 and the intracellular protein
      forkhead box P3; they exert their suppressive functions in contact-dependent as
      well as contact-independent manners. Quantitative and qualitative defects of
      Tregs were observed in patients with autoimmune diseases. Increased Treg activity
      was shown to suppress anti-tumor and anti-infection immunity. The effect of aging
      on Tregs, and the possible contribution of age-related changes of the Treg pool
      to the pathophysiology of diseases in the elderly are still poorly understood.
      Treg homeostasis depends on an intact thymic function and current data suggest
      that conversion of non-regulatory T-cells into Tregs as well as peripheral
      expansion of existing Tregs compensates for thymic involution after puberty to
      maintain constant Treg numbers. In the conventional T-cell subset, peripheral
      proliferation of T-cells is associated with replicative senescence leading to
      phenotypical and functional changes. For Tregs, different developmental stages
      were also described; however, replicative senescence of Tregs has not been
      observed yet. 

PMID- 23964278
TI  - TNFR2 Expression on CD25(hi)FOXP3(+) T Cells Induced upon TCR Stimulation of CD4
      T Cells Identifies Maximal Cytokine-Producing Effectors.
AB  - In this study, we show that CD25(hi)TNFR2(+) cells can be rapidly generated in
      vitro from circulating CD4 lymphocytes by polyclonal stimuli anti-CD3 in the
      presence of anti-CD28. The in vitro induced CD25(hi)TNFR2(+) T cells express a
      conventional regulatory T cells phenotype FOXP3(+)CTLA4(+)CD127(lo/-), but
      produce effector and immunoregulatory cytokines including IL-2, IL-10, and IFN-g.
      These induced CD25(hi)TNFR2(+) T cells do not suppress target cell proliferation,
      but enhance it instead. Thus the CD25(hi)TNFR2(+) phenotype induced rapidly
      following CD3/28 cross linking of CD4 T cells identifies cells with maximal
      proliferative and effector cytokine-producing capability. The in vivo counterpart
      of this cell population may play an important role in immune response initiation.

PMID- 23964279
TI  - Modulation of T lymphocyte calcium influx patterns via the inhibition of kv1.3
      and ikca1 potassium channels in autoimmune disorders.

PMID- 23964280
TI  - A tale of two neglected systems-structure and function of the thin- and thick
      walled sieve tubes in monocotyledonous leaves.
AB  - There is a large body of information relating to the ontogeny, development and
      the vasculature of eudicotyledonous leaves. However, there is less information
      available concerning the vascular anatomy of monocotyledonous leaves. This is
      surprising, given that there are two uniquely different phloem systems present in
      large groups such as grasses and sedges. Monocotyledonous leaves contain
      marginal, large, intermediate, and small longitudinal veins that are
      interconnected by numerous transverse veins. The longitudinal veins contain two
      metaphloem sieve tube types, which, based upon their ontogeny and position within
      the phloem, are termed early (thin-walled) and late (thick-walled) sieve tubes.
      Early metaphloem comprises sieve tubes, companion cells and vascular parenchyma
      (VP) cells, whilst the late metaphloem, contains thick-walled sieve tubes (TSTs)
      that lack companion cells. TSTs are generally adjacent to, or no more than one
      cell removed from the metaxylem. Unlike thin-walled sieve tube (ST) -companion
      cell complexes, TSTs are connected to parenchyma by pore-plasmodesma units and
      are generally symplasmically isolated from the STs. This paper addresses key
      structural and functional differences between thin- and thick-walled sieve tubes
      and explores the unique advantages of alternate transport strategies that this 5
      7 million years old dual system may offer. It would seem that these two systems
      may enhance, add to, or play a significant role in increasing the efficiency of
      solute retrieval as well as of assimilate transfer. 

PMID- 23964281
TI  - How to study deep roots-and why it matters.
AB  - The drivers underlying the development of deep root systems, whether genetic or
      environmental, are poorly understood but evidence has accumulated that deep
      rooting could be a more widespread and important trait among plants than commonly
      anticipated from their share of root biomass. Even though a distinct
      classification of "deep roots" is missing to date, deep roots provide important
      functions for individual plants such as nutrient and water uptake but can also
      shape plant communities by hydraulic lift (HL). Subterranean fauna and microbial
      communities are highly influenced by resources provided in the deep rhizosphere
      and deep roots can influence soil pedogenesis and carbon storage.Despite recent
      technological advances, the study of deep roots and their rhizosphere remains
      inherently time-consuming, technically demanding and costly, which explains why
      deep roots have yet to be given the attention they deserve. While state-of-the
      art technologies are promising for laboratory studies involving relatively small
      soil volumes, they remain of limited use for the in situ observation of deep
      roots. Thus, basic techniques such as destructive sampling or observations at
      transparent interfaces with the soil (e.g., root windows) which have been known
      and used for decades to observe roots near the soil surface, must be adapted to
      the specific requirements of deep root observation. In this review, we
      successively address major physical, biogeochemical and ecological functions of
      deep roots to emphasize the significance of deep roots and to illustrate the yet
      limited knowledge. In the second part we describe the main methodological options
      to observe and measure deep roots, providing researchers interested in the field
      of deep root/rhizosphere studies with a comprehensive overview. Addressed
      methodologies are: excavations, trenches and soil coring approaches,
      minirhizotrons (MR), access shafts, caves and mines, and indirect approaches such
      as tracer-based techniques. 

PMID- 23964282
TI  - Root resource foraging: does it matter?

PMID- 23964283
TI  - Inoculation of tomato plants with rhizobacteria enhances the performance of the
      phloem-feeding insect Bemisia tabaci.
AB  - In their natural environment, plants experience multiple biotic interactions and
      respond to this complexity in an integrated manner. Therefore, plant responses to
      herbivory are flexible and depend on the context and complexity in which they
      occur. For example, plant growth promoting rhizobacteria (PGPR) can enhance plant
      growth and induce resistance against microbial pathogens and herbivorous insects
      by a phenomenon termed induced systemic resistance (ISR). In the present study,
      we investigated the effect of tomato (Solanum lycopersicum) pre-inoculation with
      the PGPR Pseudomonas fluorescens WCS417r, on the performance of the generalist
      phloem-feeding insect Bemisia tabaci. Based on the ability of P. fluorescens
      WCS417r to prime for ISR against generalists chewing insects and necrotrophic
      pathogens, we hypothesized that pre-inoculated plants will strongly resist B.
      tabaci infestation. In contrast, we discovered that the pre-inoculation treatment
      increased the tomato plant suitability for B. tabaci which was emphasized both by
      faster developmental rate and higher survivability of nymph stages on pre
      inoculated plants. Our molecular and chemical analyses suggested that the
      phenomenon is likely to be related to: (I) the ability of the bacteria to reduce
      the activity of the plant induced defense systems; (II) a possible manipulation
      by P. fluorescens of the plant quality (in terms of suitability for B. tabaci)
      through an indirect effect on the rhizosphere bacterial community. The
      contribution of our study to the pattern proposed for other belowground
      rhizobacteria and mycorrhizal fungi and aboveground generalist phloem-feeders is
      discussed. 

PMID- 23964284
TI  - The Arabidopsis DREB2 genetic pathway is constitutively repressed by basal
      phosphoinositide-dependent phospholipase C coupled to diacylglycerol kinase.
AB  - Phosphoinositide-dependent phospholipases C (PI-PLCs) are activated in response
      to various stimuli. They utilize substrates provided by type III
      Phosphatidylinositol-4 kinases (PI4KIII) to produce inositol triphosphate and
      diacylglycerol (DAG) that is phosphorylated into phosphatidic acid (PA) by DAG
      kinases (DGKs). The roles of PI4KIIIs, PI-PLCs, and DGKs in basal signaling are
      poorly understood. We investigated the control of gene expression by basal PI-PLC
      pathway in Arabidopsis thaliana suspension cells. A transcriptome-wide analysis
      allowed the identification of genes whose expression was altered by edelfosine,
      30 MUM wortmannin, or R59022, inhibitors of PI-PLCs, PI4KIIIs, and DGKs,
      respectively. We found that a gene responsive to one of these molecules is more
      likely to be similarly regulated by the other two inhibitors. The common action
      of these agents is to inhibit PA formation, showing that basal PI-PLCs act, in
      part, on gene expression through their coupling to DGKs. Amongst the genes up
      regulated in presence of the inhibitors, were some DREB2 genes, in suspension
      cells and in seedlings. The DREB2 genes encode transcription factors with major
      roles in responses to environmental stresses, including dehydration. They bind to
      C-repeat motifs, known as Drought-Responsive Elements that are indeed enriched in
      the promoters of genes up-regulated by PI-PLC pathway inhibitors. PA can also be
      produced by phospholipases D (PLDs). We show that the DREB2 genes that are up
      regulated by PI-PLC inhibitors are positively or negatively regulated, or
      indifferent, to PLD basal activity. Our data show that the DREB2 genetic pathway
      is constitutively repressed in resting conditions and that DGK coupled to PI-PLC
      is active in this process, in suspension cells and seedlings. We discuss how this
      basal negative regulation of DREB2 genes is compatible with their stress
      triggered positive regulation. 

PMID- 23964285
TI  - Membrane "potential-omics": toward voltage imaging at the cell population level
      in roots of living plants.
AB  - Genetically encoded voltage-sensitive fluorescent proteins (VSFPs) are being used
      in neurobiology as non-invasive tools to study synchronous electrical activities
      in specific groups of nerve cells. Here we discuss our efforts to adapt this
      "light-based electrophysiology" for use in plant systems. We describe the
      production of transgenic plants engineered to express different versions of VSFPs
      that are targeted to the plasma membrane and internal membranes of root cells.
      The aim is to optically record concurrent changes in plasma membrane potential in
      populations of cells and at multiple membrane systems within single cells in
      response to various stimuli in living plants. Such coordinated electrical changes
      may globally orchestrate cell behavior to elicit successful reactions of the root
      as a whole to varying and unpredictable environments. Findings from membrane
      "potential-omics" can eventually be fused with data sets from other "omics"
      approaches to forge the integrated and comprehensive understanding that underpins
      the concept of systems biology. 

PMID- 23964288
TI  - Commentary on "MelanomaDB: a web tool for integrative analysis of melanoma
      genomic information to identify disease-associated molecular pathways".

PMID- 23964287
TI  - Functional genomics indicates yeast requires Golgi/ER transport, chromatin
      remodeling, and DNA repair for low dose DMSO tolerance.
AB  - Dimethyl sulfoxide (DMSO) is frequently utilized as a solvent in toxicological
      and pharmaceutical investigations. It is therefore important to establish the
      cellular and molecular targets of DMSO in order to differentiate its intrinsic
      effects from those elicited by a compound of interest. We performed a genome-wide
      functional screen in Saccharomyces cerevisiae to identify deletion mutants
      exhibiting sensitivity to 1% DMSO, a concentration standard to yeast chemical
      profiling studies. We report that mutants defective in Golgi/ER transport are
      sensitive to DMSO, including those lacking components of the conserved oligomeric
      Golgi (COG) complex. Moreover, strains deleted for members of the SWR1 histone
      exchange complex are hypersensitive to DMSO, with additional chromatin remodeling
      mutants displaying a range of growth defects. We also identify DNA repair genes
      important for DMSO tolerance. Finally, we demonstrate that overexpression of
      histone H2A.Z, which replaces chromatin-associated histone H2A in a SWR1
      catalyzed reaction, confers resistance to DMSO. Many yeast genes described in
      this study have homologs in more complex organisms, and the data provided is
      applicable to future investigations into the cellular and molecular mechanisms of
      DMSO toxicity. 

PMID- 23964286
TI  - The detection of microRNA associated with Alzheimer's disease in biological
      fluids using next-generation sequencing technologies.
AB  - Diagnostic tools for neurodegenerative diseases such as Alzheimer's disease (AD)
      currently involve subjective neuropsychological testing and specialized brain
      imaging techniques. While definitive diagnosis requires a pathological brain
      evaluation at autopsy, neurodegenerative changes are believed to begin years
      before the clinical presentation of cognitive decline. Therefore, there is an
      essential need for reliable biomarkers to aid in the early detection of disease
      in order to implement preventative strategies. microRNAs (miRNA) are small non
      coding RNA species that are involved in post-transcriptional gene regulation.
      Expression levels of miRNAs have potential as diagnostic biomarkers as they are
      known to circulate and tissue specific profiles can be identified in a number of
      bodily fluids such as plasma, CSF and urine. Recent developments in deep
      sequencing technology present a viable approach to develop biomarker discovery
      pipelines in order to profile miRNA signatures in bodily fluids specific to
      neurodegenerative diseases. Here we review the potential use of miRNA deep
      sequencing in biomarker identification from biological fluids and its translation
      into clinical practice. 

PMID- 23964289
TI  - Physiologic assessment of coronary artery disease by cardiac computed tomography.
AB  - Coronary artery disease (CAD) remains the leading cause of death and morbidity
      worldwide. To date, diagnostic evaluation of patients with suspected CAD has
      relied upon the use of physiologic non-invasive testing by stress
      electrocardiography, echocardiography, myocardial perfusion imaging (MPI) and
      magnetic resonance imaging. Indeed, the importance of physiologic evaluation of
      CAD has been highlighted by large-scale randomized trials that demonstrate the
      propitious benefit of an integrated anatomic-physiologic evaluation method by
      performing lesion-specific ischemia assessment by fractional flow reserve (FFR)
      widely considered the "gold" standard for ischemia assessment-at the time of
      invasive angiography. Coronary CT angiography (CCTA) has emerged as an attractive
      non-invasive test for anatomic illustration of the coronary arteries and
      atherosclerotic plaque. In a series of prospective multicenter trials, CCTA has
      been proven as having high diagnostic performance for stenosis detection as
      compared to invasive angiography. Nevertheless, CCTA evaluation of obstructive
      stenoses is prone to overestimation of severity and further, detection of
      stenoses by CCTA does not reliably determine the hemodynamic significance of the
      visualized lesions. Recently, a series of technological innovations have advanced
      the possibility of CCTA to enable physiologic evaluation of CAD, thereby creating
      the potential of this test to provide an integrated anatomic-physiologic
      assessment of CAD. These advances include rest-stress MPI by CCTA as well as the
      use of computational fluid dynamics to non-invasively calculate FFR from a
      typically acquired CCTA. The purpose of this review is to summarize the most
      recent data addressing these 2 physiologic methods of CAD evaluation by CCTA. 

PMID- 23964291
TI  - Gender difference in bone loss and vascular calcification associated with age.
AB  - BACKGROUND AND OBJECTIVES: It is widely known that both bone loss and vascular
      calcification are age-related processes. The purpose of this study was to
      investigate the relationship between coronary artery calcium (CAC) score or bone
      mineral density (BMD) with age and whether there is a gender difference factoring
      in the two conditions among healthy subjects. SUBJECTS AND METHODS: Between March
      2009 and August 2011, participants included 1727 subjects (mean age: 55+/-10
      years, M : F=914 : 813) with routine health check-ups. After being categorized
      into three groups (normal, osteopenia, and osteoporosis) according to the World
      Health Organization (WHO) diagnostic classification, we estimated BMD by dual
      energy X-ray absorptiometry (DEXA) and CAC score by dual-source CT (DSCT).
      RESULTS: There was a significant gender difference among the risk factors,
      including total-lumbar spine (1.213+/-0.176 g/cm(2) : 1.087+/-0.168 g/cm(2),
      p<0.001) and femur (1.024+/-0.131 g/cm(2) : 0.910+/-0.127 g/cm(2), p<0.001) in
      BMD by DEXA, and CAC score (68+/-227 : 27+/-116, p<0.001) in coronary artery
      calcification by DSCT. Age in male [odds ratio (OR): 1.138 {95% confidence
      interval (CI): 1.088-1.190}, p<0.001] and menopause in female subjects {OR:
      12.370 (95% CI: 3.120-49.047), p<0.001} were, respectively, independently
      associated with osteopenia. CONCLUSION: Although our results do not demonstrate a
      direct association between CAC score and BMD in both genders, there is a gender
      difference of CAC score in normal and osteopenia groups according to the WHO
      diagnostic classification. Additionally, we suggest that more specific
      therapeutic strategies be considered during any early bone loss period,
      especially in female subjects.

PMID- 23964290
TI  - The decline effect in cardiovascular medicine: is the effect of cardiovascular
      medicine and stent on cardiovascular events decline over the years?
AB  - The term decline effect is referred to a diminution of scientifically discovered
      effects over time. Reasons for the decline effect are multifaceted and include
      publication bias, selective reporting, outcomes reporting bias, regression to the
      mean, scientific paradigm shift, overshadowing and habituation, among others.
      Such effects can be found in cardiovascular medicines through medications (e.g.,
      aspirin, antithrombotics, proton pump inhibitor, beta-blockers, statins,
      estrogen/progestin, angiotensin converting enzyme inhibitor etc.), as well as
      with interventional devices (e.g., angioplasty, percutaneous coronary
      intervention, stents). The scientific community should understand the various
      dimensions of the decline effects, and effective steps should be undertaken to
      prevent or recognize such decline effects in cardiovascular medicines. 

PMID- 23964292
TI  - The Impact of Trimetazidine Treatment on Left Ventricular Functions and Plasma
      Brain Natriuretic Peptide Levels in Patients with Non-ST Segment Elevation
      Myocardial Infarction Undergoing Percutaneous Coronary Intervention.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the impact of
      treatment with oral trimetazidine (TMZ) applied before and after percutaneous
      coronary interventions (PCI) on short-term left ventricular functions and plasma
      brain natriuretic peptide (BNP) levels in patients with non-ST segment elevation
      myocardial infarction (NSTEMI) undergoing PCI. SUBJECTS AND METHODS: The study
      included 45 patients who were undergoing PCI with the diagnosis of NSTEMI. The
      patients were randomized into two groups. The first group (n=22) of the patients
      hospitalized with the diagnosis of NSTEMI was given conventional therapy plus 60
      mg TMZ just prior to PCI. Treatment with TMZ was continued for one month after
      the procedure. TMZ treatment was not given to the second group (n=23).
      Echocardiography images were recorded and plasma BNP levels were measured just
      prior to the PCI and on the 1st and 30th days after PCI. RESULTS: The myocardial
      performance index (MPI) was greater in the second group (p=0.02). In the
      comparison of BNP levels, they significantly decreased in both of the groups
      during the 30-day follow-up period (29.0+/-8 and 50.6+/-33, p<0.01 respectively).
      However, decreasing of BNP levels was higher in the group administered with TMZ.
      The decrease of left ventriclular end-diastolic volume was observed in all groups
      at 30 days after intervention, but was higher in the group administered with TMZ
      (p=0.01). CONCLUSION: Trimetazidine treatment commencing prior to PCI and
      continued after PCI in patients with NSTEMI provides improvements in MPI, left
      ventricular end diastolic volume and a decrease in BNP levels.

PMID- 23964293
TI  - Significant response to lower acetylcholine dose is associated with worse
      clinical and angiographic characteristics in patients with vasospastic angina.
AB  - BACKGROUND AND OBJECTIVES: The intracoronary injection of acetylcholine (Ach) has
      been shown to induce coronary spasms in patients with variant angina. Clinical
      significance and angiographic characteristics of patients with a significant
      response to lower Ach dosages are as-yet non-clarified compared with patients
      responding to higher Ach doses. SUBJECTS AND METHODS: A total of 3034 consecutive
      patients underwent coronary angiography with Ach provocation tests from January
      2004 to August 2010. Ach was injected in incremental doses of 20, 50, 100 ug into
      the left coronary artery. Significant coronary artery spasm was defined as focal
      or diffuse severe transient luminal narrowing (>70%) with/without chest pain or
      ST-T change on the electrocardiogram (ECG). We compared the clinical and
      angiographic characteristics of patients who responded to a lower Ach dose (20 or
      50 ug, n=556) to those that responded to a higher Ach dose (100 ug, n=860).
      RESULTS: The baseline clinical and procedural characteristics are well balanced
      between the two groups, except diabetes was higher in the lower Ach dose group
      and there were differences in medication history. After adjusting for confounding
      factors, the lower Ach dose group showed more frequent temporary ST elevation and
      atrioventricular block on the ECG. Furthermore, the group of patients who
      responded to the lower Ach dose was associated with a higher incidence of
      baseline and severe spasm than those who responded to a higher Ach dose.
      CONCLUSION: Patients with a significant response to a lower Ach dose were
      associated with more frequent ST elevation, baseline spasm, and more severe spasm
      compared with those who responded to a higher Ach dose, suggesting more intensive
      medical therapy with close clinical follow-up is required for those patients.

PMID- 23964294
TI  - Inadvertently Developed Ventricular Fibrillation during Electrophysiologic Study
      and Catheter Ablation: Incidence, Cause, and Prognosis.
AB  - BACKGROUND AND OBJECTIVES: Ventricular fibrillation (VF) can inadvertently occur
      during electrophysiologic study (EPS) or catheter ablation. We investigated the
      incidence, cause, and progress of inadvertently developed VF during EPS and
      catheter ablation. SUBJECTS AND METHODS: We reviewed patients who had developed
      inadvertent VF during EPS or catheter ablation. Patients who developed VF during
      programmed ventricular stimulation to induce ventricular tachycardia or VF were
      excluded. RESULTS: Inadvertent VF developed in 11 patients (46.7+/-9.3 years old)
      among 2624 patients (0.42%); during catheter ablation for atrial fibrillation
      (AF) in nine patients, frequent ventricular premature beats (VPBs) in one, and
      Wolff-Parkinson-White (WPW) syndrome were observed in one. VF was induced after
      internal cardioversion in six AF patients due to incorrect R-wave synchronization
      of a direct current shock. Two AF patients showed spontaneous VF induction during
      isoproterenol infusion while looking for AF triggering foci. The remaining AF
      patient developed VF after rapid atrial pacing to induce AF, but the catheter was
      accidentally moved to the right ventricular (RV) apex. A patient with VPB
      ablation spontaneously developed VF during isoproterenol infusion. The focus of
      VPB was in the RV outflow tract and successfully ablated. A patient with WPW
      syndrome developed VF after rapid RV pacing with a cycle length of 240 ms. Single
      high energy (biphasic 150-200 J) external defibrillation was successful in all
      patients, except in two, who spontaneously terminated VF. The procedure was
      uneventfully completed in all patients. At a mean follow-up period of 17.4+/-15.5
      months, no patient presented with ventricular arrhythmia. CONCLUSION: Although
      rare, inadvertent VF can develop during EPS or catheter ablation. Special caution
      is required to avoid incidental VF during internal cardioversion, especially
      under isoproterenol infusion.

PMID- 23964295
TI  - Cardiac rehabilitation increases exercise capacity with a reduction of oxidative
      stress.
AB  - BACKGROUND AND OBJECTIVES: Reactive oxygen species (ROS) mediate various
      signaling pathways that underlie vascular inflammation in atherogenesis and
      cardiovascular diseases. Cardiac rehabilitation (CR) has a variety of multiple
      beneficial effects, including anti-inflammatory effects. The purpose of the
      present study was to investigate the effects of CR on ROS in patients with
      cardiovascular diseases. SUBJECTS AND METHODS: The serum level of derivatives of
      reactive oxidative metabolites, an index of oxidative stress, was measured in 100
      patients with cardiovascular diseases before, and, subsequently, 3 and 6 months
      after, CR. A biological antioxidant potential (BAP) test was applied to assess
      the antioxidant power of the serum. RESULTS: The resting reactive oxidative
      metabolite levels decreased 3-6 months after CR {pre: 351+/-97 Carratelli unit
      (CARR U), 3 months: 329+/-77 CARR U, 6 months: 325+/-63 CARR U, all p<0.01} with
      the increase of the percentage of the predicted values of VO2 peak and the
      percentage of the predicted values of VO2 at the anaerobic threshold (VO2 AT) and
      the decrease of the B-type natriuretic peptide (BNP). The BAP test and
      antioxidative/oxidative stress ratio increased 6 months after CR. The % changes
      of the antioxidative/oxidative stress ratio was positively correlated with the %
      changes of VO2 AT, and negatively correlated with the % changes of the BNP.
      CONCLUSION: These results suggest that intensive supervised CR significantly
      improved exercise capacity, which may be attributable to an adaptive response
      involving more efficient oxidative metabolites or the increased capacity of
      endogenous anti-oxidative systems in patients with cardiovascular diseases.

PMID- 23964296
TI  - Intercoronary Communication between the Circumflex and Right Coronary Arteries
      Coexisted with Coronary Vasospasm.
AB  - Intercoronary arterial connection between normal coronary arteries is a rare
      variant of coronary anatomy in which there is open-ended circulation. It is
      distinguished from collaterals seen in the occlusive coronary artery disease. We
      report a case of bidirectional intercoronary communication between the left
      circumflex artery and the right coronary artery without occlusive coronary artery
      disease, but with left anterior descending artery spasm. 

PMID- 23964297
TI  - Spontaneous coronary artery dissection mimicking coronary spasm diagnosed by
      intravascular ultrasonography.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare and occasionally life
      threatening cause of acute coronary syndrome. Patients may present with clinical
      scenarios ranging from angina pectoris to cardiogenic shock to sudden cardiac
      death, and it may be a potentially life-threatening condition if not recognized.
      However, its etiology, pathophysiology and optimal therapeutic strategies have
      not been well understood. SCAD is diagnosed on the basis of coronary angiography,
      but complementary techniques as such intravascular ultrasound (IVUS) and optical
      coherence tomography should be considered for diagnostic clarification where
      appropriate. Likewise, the selection of treatment strategy depends upon the
      clinical manifestation, location and the extent of dissection and amount of
      ischemic myocardium at risk. Herein, we present the case of a 35-year-old woman
      who presented with acute myocardial infarction. She was diagnosed by IVUS with
      spontaneous diffuse dissection of the left anterior descending artery without
      atheroma, treated with percutaneous coronary stenting, and had a favorable
      clinical course and was discharged on medical therapy. 

PMID- 23964298
TI  - Pulmonary Alveolar Hemorrhage after Clopidogrel Use for ST Elevation Myocardial
      Infarction.
AB  - Combination treatment of antiplatelet drugs containing aspirin and clopidogrel
      reduces systemic ischemic events after percutaneous coronary intervention (PCI)
      in high risk patients. However, this combination treatment of antiplatelet drugs
      is associated with increased risk of nonfatal and fatal bleeding. Diffuse
      alveolar hemorrhage after PCI is a rare complication that has been mostly
      reported in association with glycoprotein IIb/IIIa inhibitors. We report the case
      of a 62-year-old man who presented with ST elevation myocardial infarction and
      suffered a diffuse alveolar hemorrhage after clopidogrel use following primary
      PCI. 

PMID- 23964299
TI  - A delayed, unusual non-cardiogenic pulmonary edema after intravascular
      administration of non-ionic, low osmolar radiocontrast media for coronary
      angiography.
AB  - Non-cardiogenic pulmonary edema (NCPE) is a rare adverse reaction to iodinated
      radiocontrast media (RCM), in which all previous cases were immediate reactions.
      A 56-year-old male was given iopamidol, a non-ionic, low osmolar RCM, during
      coronary artery angiography. He developed pulmonary edema and fever a day after
      the procedure. Despite diuretic therapy, the patient's pulmonary edema worsened
      and his high fever persisted. The patient's pulmonary edema was eventually
      resolved with intravenous steroid treatment. We interpreted the patient's
      condition as NCPE manifesting as a delayed reaction to RCM. To our knowledge, our
      case is the first to show NCPE as a delayed hypersensitivity reaction. 

PMID- 23964300
TI  - Severe Pulmonary Hypertension in Primary Sjogren's Syndrome.
AB  - A 65 year-old female with a history of xerostomia and xerophthalmia was presented
      with dyspnea on exertion (New York Heart Association class III). Echocardiography
      and cardiac catheterization demonstrated severe pulmonary hypertension (PH).
      Laboratory examinations showed positive anti-nuclear and anti-Ro/SS-A antibodies.
      Schirmer's test was positive and salivary gland scintigraphy revealed severely
      decreased tracer uptakes in both parotid and submandibular glands. By excluding
      other possible causes of PH during further examinations, she was diagnosed with
      severe PH associated with primary Sjogren's syndrome. Her dyspnea symptom was
      much improved with endothelin receptor antagonist and azathioprine. 

PMID- 23964301
TI  - Bicuspid Aortic Valve and Coronary Artery Stenosis in the Cardiac CT.

PMID- 23964302
TI  - Hantaviruses as zoonotic pathogens in Germany.
AB  - BACKGROUND: Hantavirus disease is a zoonosis of increasing clinical importance. A
      new incidence peak was reached in Germany in 2012, with more than 2800 reported
      cases. These viruses are transmitted from small mammals to human beings. The
      disease begins with high fever and non-pathognomonic manifestations that can end
      in shock and organ failure. METHODS: This article is based on a selective
      literature search, on the authors' experiences at the National Referral
      Laboratory for Hantavirus Infections (Nationales Konsiliarlaboratorium fur
      Hantaviren), and on published recommendations from Germany and abroad. RESULTS:
      Two hantavirus species cause clinically relevant infections in Germany. Puumala
      virus, which is transmitted by bank voles, causes large outbreaks of disease
      every 2 to 3 years in the southwestern and western regions of Germany and in the
      Bavarian Forest. Dobrava-Belgrad virus, transmitted by striped field mice, causes
      infections in the north and east of the country. Serological tests are available
      for primary and confirmatory diagnosis; moreover, viral nucleic acids can be
      amplified in the early phase of illness and compared with the viral nucleic acids
      from the reservoir hosts of the corresponding type of infection. Infections with
      American types of hantavirus have ca. 35% case fatality, and hantaviruses from
      southeastern Europe and Asia are also highly pathogenic; in contrast, the febrile
      illnesses caused by hantaviruses in Germany are usually relatively mild.
      CONCLUSION: When persons living in high-risk areas present with fever of unknown
      origin or with renal dysfunction of unknown origin, physicians should consider
      the possibility of a hantavirus infection and should initiate the appropriate
      diagnostic evaluation.

PMID- 23964304
TI  - Rheumatoid arthritis--early diagnosis and disease management.
AB  - BACKGROUND: 0.5% to 0.8% of all adults suffer from rheumatoid arthritis (RA). The
      main considerations for persons with new-onset RA are early diagnosis, disease
      modifying anti-rheumatic drugs (DMARDs), remission, and interdisciplinary
      treatment. METHOD: As part of the process of creating a new S3 guideline on the
      management of early RA and a new S1 guideline on stage-adapted pharmacotherapy
      for RA, the authors conducted a selective search and review of the literature and
      specifically updated it to 20 March 2013. RESULTS: In patients presenting with
      joint inflammation, the diagnosis of RA can be directly confirmed (positive
      predictive value, 85% to 97%), and its prognosis assessed, on the basis of the
      following findings: joint examination, acute phase reaction, serology (rheumatoid
      factor [RF], antibody against citrullinated peptides/proteins [ACPA], and
      duration of symptoms (ACR/Eular classification criteria, 2010). Early, remission
      oriented and adapted treatment with DMARDs ("treating to target") leads to
      several years of normal bodily function without disability in 40% to 60% of
      patients. Treatment by an interdisciplinary team promotes the achievement of this
      goal. The risks associated with this form of treatment are low, with a dropout
      rate of less than 1 per 100 patient-years. Life-threatening complications are
      rare. CONCLUSION: Early diagnosis, intervention with DMARDs in the first three
      months of disease, and the achievement of a remission minimize the adverse
      sequelae of RA. The sequential introduction of DMARDs, including biological
      agents in non-responders, as part of a treat-to-target concept optimizes the long
      term outcome, as has been demonstrated in clinical trials for periods of up to
      eight years.

PMID- 23964305
TI  - Quality assurance would be welcome.

PMID- 23964303
TI  - The diagnosis, treatment and follow-up of extracranial carotid stenosis.
AB  - BACKGROUND: Extracranial atherosclerotic lesions of the carotid bifurcation cause
      10% to 20% of all cases of cerebral ischemia. Until now, there have been no
      comprehensive evidence- and consensus-based recommendations for the management of
      patients with extracranial carotid stenosis in Germany and Austria. METHODS: The
      literature was systematically searched for pertinent publications (1990-2011). On
      the basis of 182 randomized clinical trials (RCTs) and 308 systematic reviews, 30
      key questions were answered and evidence-based recommendations were issued.
      RESULTS: The prevalence of extracranial carotid stenosis is more than 5% from age
      65 onward. Men are affected twice as frequently as women. The most important
      diagnostic technique is Doppler- and color-coded duplex ultrasonography. RCTs
      have shown that the treatment of high-grade asymptomatic carotid stenosis with
      carotid endarterectomy (CEA) can lower the 5-year risk of stroke from 11% to 5%.
      Intensive conservative treatment may lower the stroke risk still further.
      Moreover, RCTs have shown that CEA for symptomatic 50% to 99% carotid stenosis
      lowers the 5-year stroke risk by 5% to 16%. Meta-analyses of the 13 available
      RCTs comparing carotid artery stenting (CAS) with CEA have shown that CAS is
      associated with a 2% to 2.5% higher risk of periprocedural stroke or death and
      with a 0.5% to 1% lower risk of periprocedural myocardial infarction. If no
      particular surgical risk factors are present, CEA is the standard treatment for
      high-grade carotid stenosis. CAS may be considered as an alternative to CEA if
      the rate of procedure-related stroke or death can be kept below 3% or 6% for
      asymptomatic and symptomatic stenosis, respectively. CONCLUSION: Further studies
      are needed so that better selection criteria can be developed for individually
      tailored treatment.

PMID- 23964306
TI  - High-quality logistical concept for interhospital transport is crucial.

PMID- 23964307
TI  - In Reply.

PMID- 23964308
TI  - Localized removal of layers of metal, polymer, or biomaterial by ultrasound
      cavitation bubbles.
AB  - We present an ultrasonic device with the ability to locally remove deposited
      layers from a glass slide in a controlled and rapid manner. The cleaning takes
      place as the result of cavitating bubbles near the deposited layers and not due
      to acoustic streaming. The bubbles are ejected from air-filled cavities
      micromachined in a silicon surface, which, when vibrated ultrasonically at a
      frequency of 200 kHz, generate a stream of bubbles that travel to the layer
      deposited on an opposing glass slide. Depending on the pressure amplitude, the
      bubble clouds ejected from the micropits attain different shapes as a result of
      complex bubble interaction forces, leading to distinct shapes of the cleaned
      areas. We have determined the removal rates for several inorganic and organic
      materials and obtained an improved efficiency in cleaning when compared to
      conventional cleaning equipment. We also provide values of the force the bubbles
      are able to exert on an atomic force microscope tip. 

PMID- 23964309
TI  - Micro- and nanofluidic technologies for epigenetic profiling.
AB  - This short review provides an overview of the impact micro- and nanotechnologies
      can make in studying epigenetic structures. The importance of mapping histone
      modifications on chromatin prompts us to highlight the complexities and
      challenges associated with histone mapping, as compared to DNA sequencing. First,
      the histone code comprised over 30 variations, compared to 4 nucleotides for DNA.
      Second, whereas DNA can be amplified using polymerase chain reaction, chromatin
      cannot be amplified, creating challenges in obtaining sufficient material for
      analysis. Third, while every person has only a single genome, there exist
      multiple epigenomes in cells of different types and origins. Finally, we
      summarize existing technologies for performing these types of analyses. Although
      there are still relatively few examples of micro- and nanofluidic technologies
      for chromatin analysis, the unique advantages of using such technologies to
      address inherent challenges in epigenetic studies, such as limited sample
      material, complex readouts, and the need for high-content screens, make this an
      area of significant growth and opportunity. 

PMID- 23964310
TI  - Epigallocatechin gallate attenuates L-DOPA-induced apoptosis in rat PC12 cells.
AB  - In this study, the protective effects of EGCG on L-3,4-dihydroxyphenylalanine (L
      DOPA)-induced oxidative cell death in catecholaminergic PC12 cells, the in vitro
      model of Parkinson's disease, were investigated. Treatment with L-DOPA at
      concentrations higher than 150 uM caused cytotoxicity in PC12 cells, as
      determined using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) assay and flow cytometry detection. The apoptotic ratio was similar in
      cells treated with 100 uM EGCG plus 150 uM L-DOPA (5.02%) and the control (0.96%)
      (P > 0.05), and was lower than that of cells treated with L-DOPA only (32.24%, P
      < 0.05). The generation level of ROS (% of control) in cells treated with EGCG
      plus L-DOPA was lower than that in cells treated with L-DOPA only (123.90% vs
      272.32%, P < 0.05). The optical density in production of TBARS in cells treated
      with L-DOPA only was higher than that in the control (0.27 +/- 0.05 vs 0.08 +/-
      0.04, P < 0.05), and in cells treated with EGCG only (0.14 +/- 0.02, P < 0.05),
      and EGCG plus L-DOPA (0.13 +/- 0.02, P < 0.05). The intracellular level of GSH in
      cells treated with EGCG plus L-DOPA was higher than that in cells treated with L
      DOPA only (233.25 +/- 16.44 vs 119.23 +/- 10.25, P < 0.05). These results suggest
      that EGCG protects against L-DOPA-induced oxidative apoptosis in PC12 cells, and
      might be a potent neuroprotective agent. 

PMID- 23964311
TI  - Effects of perilla oil on plasma concentrations of cardioprotective (n-3) fatty
      acids and lipid profiles in mice.
AB  - The aim of this study was to examine the effects of perilla oil as well as
      several vegetable oils, including flaxseed oil, canola oil, and rice bran oil on
      plasma levels of cardioprotective (n-3) polyunsaturated fatty acids in mice by
      feeding each vegetable oil for a period of eight weeks. Concentrations of
      docosapentaenoic acid (DHA) and eicosapentaenoic acid (EPA), fish-based (n-3)
      polyunsaturated fatty acids, showed an increase in the plasma of mice fed perilla
      and flaxseed oils compared to those of mice in the control group (P < 0.05),
      whereas rice bran and canola oils did not alter plasma DPA and EPA
      concentrations. Arachidonic acid concentration was increased by feeding rice bran
      oil (P < 0.05), but not canola, flaxseed, or perilla oil. In addition, oleic
      acid, linoleic acid, and docosahexaenoic acid concentrations were altered by
      feeding dietary rice bran, canola, perilla, and flaxseed oils. Findings of this
      study showed that perilla oil, similar to flaxseed oil, is cardioprotective and
      could be used as an alternative to fish oil or even flaxseed oil in animal
      models. 

PMID- 23964312
TI  - Laxative effect of peanut sprout extract.
AB  - Certain phenolic compounds are known to exhibit laxative properties. Seed
      sprouts, such as those of peanut, are known to promote de novo biosynthesis of
      phenolic compounds. This study was conducted to examine the potential laxative
      properties of 80% (v/v) ethanolic extract of peanut sprout (PSE), which contains
      a high concentration of phenolic compounds such as resveratrol. For this, SD rats
      were orally administered PSE while a control group was incubated with saline.
      Laxative effects were examined in both groups of rats. Constipation induced by
      loperamide in SD rats was improved by administration of PSE. Constipated rats
      showed increased intestinal movement of BaSO4 upon administration of PSE compared
      to the control, and the groups administered 100 or 1,000 mg PSE/kg bw were not
      significantly different in transit time of the indicator. However, colon length
      was not statistically different among the experimental groups, although it was
      longer in the group incubated with 1 g PSE/kg bw compared to other groups.
      Further, there was no significant difference in stool number among the
      experimental groups. Taken together, these findings show that PSE has a laxative
      effect in a rat model of loperamide-induced constipation. 

PMID- 23964313
TI  - Anti-obesity effects of hot water extract from Wasabi (Wasabia japonica Matsum.)
      leaves in mice fed high-fat diets.
AB  - The anti-obesity effects of a hot water extract from wasabi (Wasabia japonica
      Matsum.) leaves (WLE), without its specific pungent constituents, such as allyl
      isothiocyanate, were investigated in high fat-diet induced mice. C57J/BL mice
      were fed a high-fat diet (control group) or a high-fat diet supplemented with 5%
      WLE (WLE group). Physical parameters and blood profiles were determined. Gene
      expression associated with lipid metabolism in liver and white adipose tissue
      were analyzed. After 120 days of feeding, significantly lower body weight gain,
      liver weight and epididymal white adipose tissue weight was observed in the WLE
      group compared to the control group. In liver gene expression within the WLE
      group, PPARalpha was significantly enhanced and SREBP-1c was significantly
      suppressed. Subsequent downstream genes controlled by these regulators were
      significantly suppressed. In epididymal white adipose tissue of the WLE group,
      expression of leptin, PPARgamma, and C/EBPalpha were significantly suppressed and
      adiponectin was significantly enhanced. Acox, related to fatty acid oxidization
      in adipocytes, was also enhanced. Our results demonstrate that the WLE dietary
      supplement induces mild suppression of obesity in a high-fat diet induced mice,
      possibly due to suppression of lipid accumulation in liver and white adipose
      tissue. 

PMID- 23964314
TI  - Bamboo salt attenuates CCl4-induced hepatic damage in Sprague-Dawley rats.
AB  - Bamboo salt, a Korean folk medicine, is prepared with solar salt (sea salt) and
      baked several times at high temperatures in a bamboo case. In this study, we
      compared the preventive effects of bamboo salt and purified and solar salts on
      hepatic damage induced by carbon tetrachloride in Sprague-Dawley rats. Compared
      with purified and solar salts, bamboo salts prevented hepatic damage in rats, as
      evidenced by significantly reduced serum levels of aspartate aminotransferase,
      alanine aminotransferase, and lactate dehydrogenase (P < 0.05). Bamboo salt
      (baked 9*) triggered the greatest reduction in these enzyme levels. In addition,
      it also reduced the levels of the proinflammatory cytokines interleukin (IL)-6,
      interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha. Histopathological
      sections of liver tissue demonstrated the protective effect of bamboo salt,
      whereas sections from animals treated with the other salt groups showed a greater
      degree of necrosis. We also performed reverse transcription-polymerase chain
      reaction and western blot analyses of the inflammation-related genes iNOS, COX-2,
      TNF-alpha, and IL-1beta in rat liver tissues. Bamboo salt induced a significant
      decrease (~80%) in mRNA and protein expression levels of COX-2, iNOS, TNF-alpha,
      and IL-1beta, compared with the other salts. Thus, we found that baked bamboo
      salt preparations could prevent CCl4-induced hepatic damage in vivo. 

PMID- 23964316
TI  - The effect of fucoxanthin rich power on the lipid metabolism in rats with a high
      fat diet.
AB  - This study determined the effects of fucoxanthin on gene expressions related to
      lipid metabolism in rats with a high-fat diet. Rats were fed with normal fat diet
      (NF, 7% fat) group, high fat diet group (HF, 20% fat), and high fat with 0.2%
      fucoxanthin diet group (HF+Fxn) for 4 weeks. Body weight changes and lipid
      profiles in plasma, liver, and feces were determined. The mRNA expressions of
      transcriptional factors such as sterol regulatory element binding protein (SREBP)
      1c, Carnitine palmitoyltransferase-1 (CPT1), Cholesterol 7alpha-hydroxylase1
      (CYP7A1) as well as mRNA expression of several lipogenic enzymes were determined.
      Fucoxanthin supplements significantly increased plasma high density lipoprotein
      (HDL) concentration (P < 0.05). The hepatic total lipids, total cholesterols, and
      triglycerides were significantly decreased while the fecal excretions of total
      lipids, cholesterol, and triglycerides were significantly increased in HF+Fxn
      group (P < 0.05). The mRNA expression of hepatic Acetyl-CoA carboxylase (ACC),
      Fatty acid synthase (FAS), and Glucose-6-phosphate dehydrogenase (G6PDH) as well
      as SREBP-1C were significantly lower in HF+Fxn group compared to the HF group (P
      < 0.05). The hepatic mRNA expression of Hydroxy-3-methylglutaryl coenzyme A (HMG
      CoA) and Acyl-CoA cholesterol acyltransferase (ACAT) were significantly low while
      lecithin-cholesterol acyltransferase (LCAT) was significantly high in the HF+Fxn
      group (P < 0.05). There was significant increase in mRNA expression of CPT1 and
      CYP7A1 in the HF+Fxn group, compared to the HF group (P < 0.05). In conclusion,
      consumption of fucoxanthin is thought to be effective in improving lipid and
      cholesterol metabolism in rats with a high fat diet. 

PMID- 23964315
TI  - Effects of parental folate deficiency on the folate content, global DNA
      methylation, and expressions of FRalpha, IGF-2 and IGF-1R in the postnatal rat
      liver.
AB  - We examined the effect of parental folate deficiency on the folate content,
      global DNA methylation, folate receptor-alpha (FRalpha), insulin-like-growth
      factor-2 (IGF-2) and -1 receptor (IGF-1R) in the liver and plasma homocysteine in
      the postnatal rat. Male and female rats were randomly fed a folic acid-deficient
      (paternal folate-deficient, PD and maternal folate-deficient, MD), or folic acid
      supplemented diet (paternal folate-supplemented, PS and maternal-folate
      supplemented, MS) for four weeks. They were mated and grouped accordingly: PSxMS,
      PSxMD, PDxMS, and PDxMD. Pups were killed on day 21 of lactation. The hepatic
      folate content was markedly reduced in the PDxMD and PSxMD and PDxMS as compared
      with the PSxMS group. The hepatic global DNA methylation was decreased in the
      PDxMS and PSxMD groups as much as in the PDxMD group, and all the three groups
      were significantly lower as compared to the PSxMS group. There were no
      significant differences in the hepatic FRalpha, IGF-2 and IGF-1R expressions
      among the groups. Positive correlations were found between the hepatic folate
      content and global DNA methylation and protein expressions of FRalpha, IGF-2 and
      IGF-1R, whereas an inverse correlation was found between hepatic folate content
      and plasma homocysteine level in the 3-week-old rat pup. The results of this
      study show that both paternal and maternal folate deficiency at mating can
      influence the folate content and global DNA methylation in the postnatal rat
      liver. 

PMID- 23964317
TI  - Dietary carnosic acid suppresses hepatic steatosis formation via regulation of
      hepatic fatty acid metabolism in high-fat diet-fed mice.
AB  - In this study, we examined the hepatic anti-steatosis activity of carnosic acid
      (CA), a phenolic compound of rosemary (Rosmarinus officinalis) leaves, as well as
      its possible mechanism of action, in a high-fat diet (HFD)-fed mice model. Mice
      were fed a HFD, or a HFD supplemented with 0.01% (w/w) CA or 0.02% (w/w) CA, for
      a period of 12 weeks, after which changes in body weight, blood lipid profiles,
      and fatty acid mechanism markers were evaluated. The 0.02% (w/w) CA diet resulted
      in a marked decline in steatosis grade, as well as in homeostasis model
      assessment of insulin resistance (HOMA-IR) index values, intraperitoneal glucose
      tolerance test (IGTT) results, body weight gain, liver weight, and blood lipid
      levels (P < 0.05). The expression level of hepatic lipogenic genes, such as
      sterol regulating element binding protein-1c (SREBP-1c), liver-fatty acid binding
      protein (L-FABP), stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase
      (FAS), was significantly lower in mice fed 0.01% (w/w) CA and 0.02% (w/w) CA
      diets than that in the HFD group; on the other hand, the expression level of beta
      oxidation-related genes, such as peroxisome proliferator-activated receptor alpha
      (PPAR-alpha), carnitine palmitoyltransferase 1 (CPT-1), and acyl-CoA oxidase
      (ACO), was higher in mice fed a 0.02% (w/w) CA diet, than that in the HFD group
      (P < 0.05). In addition, the hepatic content of palmitic acid (C16:0),
      palmitoleic acid (C16:1), and oleic acid (C18:1) was significantly lower in mice
      fed the 0.02% (w/w) CA diet than that in the HFD group (P < 0.05). These results
      suggest that orally administered CA suppressed HFD-induced hepatic steatosis and
      fatty liver-related metabolic disorders through decrease of de novo lipogenesis
      and fatty acid elongation and increase of fatty acid beta-oxidation in mice. 

PMID- 23964318
TI  - Glycemic index of dietary formula may not be predictive of postprandial
      endothelial inflammation: a double-blinded, randomized, crossover study in non
      diabetic subjects.
AB  - The emerging role of endothelial inflammation in diabetes has stimulated research
      interest in the effects of nutrition on related indices. In the current study we
      investigated whether the nutrient composition of dietary formula as reflected in
      glycemic index (GI) may be predictive of postprandial endothelial inflammation in
      non-diabetic subjects. A double-blinded, randomized, crossover study was
      conducted in non-diabetic subjects (n = 8/group). Each subject consumed three
      types of diabetes-specific dietary formulas (high-fiber formula [FF], high
      monounsaturated fatty acid (MUFA) formula [MF] and control formula [CF])
      standardized to 50 g of available carbohydrates with a 1-week interval between
      each. The mean glycemic index (GI) was calculated and 3-hour postprandial
      responses of insulin, soluble intercellular adhesion molecule-1 (sICAM-1),
      nitrotyrosine (NT) and free fatty acids (FFA) were measured. The MF showed the
      lowest mean GI and significantly low area under the curve (AUC) for insulin (P =
      0.038), but significantly high AUCs for sICAM-1 (P < 0.001) and FFA (P < 0.001)
      as compared to the CF and FF. The FF showed intermediate mean GI, but
      significantly low AUC for NT (P < 0.001) as compared to the CF and MF. The mean
      GI was not positively correlated to any of the inflammatory markers evaluated,
      and in fact negatively correlated to changes in FFA (r = -0.473, P = 0.006).
      While the MF with the lowest GI showed the highest values in most of the
      inflammatory markers measured, the FF with intermediate GI had a modest
      beneficial effect on endothelial inflammation. These results suggest that
      nutrient composition of dietary formula as reflected in the GI may differently
      influence acute postprandial inflammation in non-diabetic subjects. 

PMID- 23964319
TI  - Effect of milk and milk products consumption on physical growth and bone mineral
      density in Korean adolescents.
AB  - This study was conducted to investigate the relationship among the current status
      of calcium intake from milk and milk products, physical growth and bone mineral
      density in 664 male and female middle school and high school students aged 15-17
      years. In the study, the current status of calcium intake from milk and milk
      products was analyzed, and the height, body composition, and bone mineral density
      of the right heel bone (calcaneus) were measured. The daily calcium intake of
      milk and milk products was calculated as the 'dairy equivalent of calcium', which
      is the calcium content in 200 mL of white milk. The cutoffs of tertiles of the
      dairy equivalent of calcium were calculated and then the subjects were
      categorized into 3 groups according to the tertiles, Q1 group (lower intake
      group), Q2 group (middle intake group) and Q3 group (upper intake group). The
      daily calcium intake of milk and milk products in Q1, Q2 and Q3 groups was 16.2
      mg, 99.7 mg, and 284.0 mg, respectively, and the ratio of milk and milk product
      consumption to the daily total calcium intake was 5.4%, 27.4%, and 49.7%,
      respectively. The ratio of total calcium intake to the daily recommended intake
      in study subjects was 30.5% in Q1, 42.3% in Q2, and 60.7% in Q3, with significant
      differences (P < 0.05). Height, body weight, BMI, and % of body fat in three
      tertile groups (Q1, Q2 and Q3) were not significantly different. However, the T
      scores for bone mineral density in female students in three tertile groups (Q1,
      Q2 and Q3) was significantly different (P < 0.05). The study showed that the
      intake of milk and milk products in adolescents, particularly in girls, can
      improve the bone mineral density without increasing body weight, and thus
      confirmed that milk intake is important in adolescence. 

PMID- 23964320
TI  - Determinants of neural tube defect (NTD)-protective circulating concentrations of
      folate in women of child-bearing age in the US post-folic acid fortification era.
AB  - We evaluated folate status of child-bearing age women diagnosed with abnormal pap
      smear in the US post-folic acid (FA) fortification era and assessed the
      determinants of NTD-protective and supra-physiologic (SP) concentrations of
      folate. The distribution of 843 women according to NTD-protective concentrations
      of RBC folate, plasma folate and SP concentrations of plasma folate were tested
      in relation to demographic and life-style factors. Logistic regression models
      specified NTD-protective concentrations of RBC and plasma folate or SP
      concentrations of plasma folate as dependent variables and demographic and life
      style factors as independent predictors of interest. More than 82% reached NTD
      protective concentrations of RBC and plasma folate and ~30% reached SP
      concentrations of plasma folate. FA supplement use was associated with having SP
      concentrations of plasma folate rather than NTD-protective concentrations of
      folate. African American (AA) women and smokers were significantly less likely to
      achieve NTD-protective concentrations of RBC and plasma folate. A large majority
      of women reached NTD-protective concentrations of folate with the current level
      of FA fortification without using supplementary FA. Therefore, the remaining
      disparities in AA women and in smokers should be addressed by targeted individual
      improvements in folate intake. 

PMID- 23964321
TI  - Validation of self-reported height and weight in fifth-grade Korean children.
AB  - Height and weight are important indicators to calculate Body Mass Index (BMI);
      measuring height and weight directly is the most exact method to get this
      information. However, it is ineffective in terms of cost and time on large
      population samples. The aim of our study was to investigate the validity of self
      reported height and weight data compared to our measured data in Korean children
      to predict obese status. Four hundred twenty-two fifth-grade (mean age 10.5 +/-
      0.5 years) children who had self-reported and measured height and weight data
      were final subjects for this study. Overweight/obese was defined as a BMI of or
      above the 85th percentile of the gender-specific BMI for age in the 2007 Korean
      National Growth Charts or a BMI of 25 or higher (underweight : < 5th, normal : >=
      5th to < 85th, overweight : >= 85th to < 95th). The differences between self
      reported and measured data were tested using paired t-test. Differences based on
      overweight/obese status were tested using analysis of variance (ANOVA) and linear
      trends. Pearson's correlation and Cohen's kappa were tested to examine agreements
      between the self-reported and measured data. Although measured and self-reported
      height, weight and BMI were significantly different and children tended to
      overreport their height and underreport their weight, the correlation between the
      two methods of height, weight and BMI were high (r = 0.956, 0.969, 0.932,
      respectively; all P < 0.001), and both genders reported their overweight/non
      overweight status accurately (Cohen's kappa = 0.792, P < 0.001). Although there
      were differences between the self-reported and our measured methods, the self
      reported weight and height was valid enough to classify overweight/obesity status
      correctly, especially in non-overweight/obese children. Due to bigger
      underestimation of weight and overestimation of height in obese children,
      however, we need to be aware that the self-reported anthropometric data were less
      accurate in overweight/obese children than in non-overweight/obese children. 

PMID- 23964322
TI  - Associations between dietary patterns and screen time among Korean adolescents.
AB  - Data are limited on the association between dietary patterns and screen time
      among Korean adolescents. The present study identified dietary patterns of 691
      adolescents, aged 13-18 years, who had participated in the Third Korean National
      Health and Nutrition Examination Survey (KNHANES III) and analyzed their
      associations with screen time. Screen time was defined as the time spent watching
      TV, using a computer, or playing video games was calculated as a sum of all these
      times. Dietary patterns and their factor scores were derived from a food
      frequency questionnaire using the factor analysis method. To analyze the
      association between dietary patterns and screen time, we conducted multiple
      linear regression analysis. We also performed multiple logistic regression
      analysis to estimate odds ratios (OR) of excessive screen time (2 hours or longer
      per day) and 95% confidence intervals (CI). We identified 2 dietary patterns
      labeled "the Korean healthy dietary pattern" and "the Western diet and fast foods
      pattern". The former included mixed grains, legumes, potatoes, red meat, eggs,
      fish, dairy products, fruits, vegetables, seaweeds, and mushrooms, whereas the
      latter included noodles, bread, red meat, poultry, fast foods, snack, and soft
      drinks. After controlling for potential confounding factors, factor scores for
      the Korean healthy dietary pattern were inversely associated (P-value for trend <
      0.01) and those for the Western diet and fast foods pattern were positively
      associated with the screen time (P-value for trend < 0.01). Adolescents in the
      top tertile of the scores for the Korean healthy dietary pattern had a
      multivariable-adjusted OR [95% CI] of 0.44 (0.25-0.75) for excessive screen time
      compared with those in the lowest tertile. On the basis of these findings,
      adolescents who have excessive screen time may need to be encouraged to consume a
      more healthy diet. 

PMID- 23964323
TI  - Effects of sensory education based on classroom activities for lower grade school
      children.
AB  - This study is to verify the effects of sensory education based on classroom
      activities for 2(nd) and 3(rd) grade children. The hypothesis is that children
      who participated in sensory education would demonstrate positive changes in
      eating behaviors through sensory experiences. The sensory education program
      consists of 12 lessons. Twenty-six children were being recruited from one school
      in Changwon, Korea. Two control groups, one of which was the same age as the
      educated group and the other group of sixth graders, were selected by random
      sampling from the same school. Children answered a self-administered
      questionnaire. The parents (n = 20) of the children who participated in the
      program, took part in evaluating the program through self-administered
      questionnaires after the program ended. The questionnaire contained variables of
      general characteristics, education satisfaction, nutrition knowledge, eating
      attitude and behavior concerning unfamiliar foods. The score of nutrition
      knowledge was improved in educated children (P < 0.05). Food neophobia score
      towards unfamiliar foods (P < 0.05) was increased in educated children, but there
      are no changes in eating behaviors in all groups towards unfamiliar foods. In
      conclusion, sensory education is useful for having a positive eating attitude
      among children. Its consistent implementation could lead to healthier and well
      balanced eating behaviors for children. 

PMID- 23964324
TI  - Harmony of Duet over Solo: Use of Midazolam or Propofol for Sedative Endoscopy in
      Pediatric Patients.

PMID- 23964325
TI  - Diagnosis of subepithelial lesion: still "tissue is the issue".

PMID- 23964326
TI  - Continue or discontinue dual antiplatelet therapy in major surgical or endoscopic
      procedures.

PMID- 23964327
TI  - The role of colonoscopy in inflammatory bowel disease.
AB  - An endoscopic evaluation, particularly ileocolic mucosal and histological
      findings, is essential for the diagnosis of inflammatory bowel disease (IBD). The
      introduction of antitumor necrosis factor agents has changed the therapeutic
      paradigm of patients with IBD, but an endoscopic evaluation is more important to
      guide therapeutic decision-making. In the future, endoscopy with a histological
      evaluation will be increasingly used in patients with IBD. Both Crohn colitis and
      ulcerative colitis result in an increased incidence of colorectal carcinoma.
      Thus, surveillance colonoscopy is important to detect early neoplastic lesions.
      Surveillance ileocolonoscopy has also changed recently from multiple random
      biopsies to pancolonic dye spraying with targeted biopsies of abnormal areas. 

PMID- 23964328
TI  - Small bowel endoscopy in inflammatory bowel disease.
AB  - Crohn disease (CD) is a chronic inflammatory bowel disease that affects the
      entire gastrointestinal tract but is most frequently localized to the large and
      small bowel. Small bowel endoscopy helps with the differential diagnosis of CD in
      suspected CD patients. Early diagnosis of CD is preferable for suspected CD
      conditions to improve chronic inflammatory infiltrates, fibrosis. Small bowel
      endoscopy can help with the early detection of active disease, thus leading to
      early therapy before the onset of clinical symptoms of established CD. Some
      patients with CD have mucosal inflammatory changes not in the terminal ileum but
      in the proximal small bowel. Conventional ileocolonoscopy cannot detect ileal
      involvement proximal to the terminal ileum. Small bowel endoscopy, however, can
      be useful for evaluating these small bowel involvements in patients with CD.
      Small bowel endoscopy by endoscopic balloon dilation (EBD) enables the treatment
      of small bowel strictures in patients with CD. However, many practical issues
      still need to be addressed, such as endoscopic findings for early detection of
      CD, application compared with other imaging modalities, determination of the
      appropriate interval for endoscopic surveillance of small bowel lesions in
      patients with CD, and long-term prognosis after EBD. 

PMID- 23964329
TI  - Computed tomography enterography for evaluation of inflammatory bowel disease.
AB  - Computed tomography enterography (CTE) has become a main modality for the
      evaluation of inflammatory bowel disease (IBD). It simultaneously offers
      visualization of the small bowel and extraintestinal status, which is helpful for
      diagnosing IBD. Crohn disease has long segmental enhancing wall thickening
      related with the eccentric longitudinal distribution. In addition, mural
      stratification, fibrofatty proliferation, positive comb sign by increased
      mesenteric vascularity and internal/perianal fistula are characteristics of Crohn
      disease and can be identified on CTE. Short segmental inflammatory wall
      thickening and the central low attenuated lymph nodes are favorable CT finding of
      intestinal tuberculosis. A geographic, relatively large, and deep penetrating
      ulcer with bowel wall thickening and mural hyperenhancement in ileocecal area are
      characteristics of intestinal Behcet disease. Each of CTE findings for the IBDs
      is helpful for differential diagnosis. The main disadvantage of this technique is
      the requisite radiation exposure of patients, particularly in young patients.
      However, recent development of advanced CT techniques is promising for radiation
      dose reduction without compromising diagnostic image quality. 

PMID- 23964330
TI  - A review of current disinfectants for gastrointestinal endoscopic reprocessing.
AB  - Gastrointestinal endoscopy is gaining popularity for diagnostic and therapeutic
      purposes. However, concerns over endoscope-related nosocomial infections are
      increasing, together with interest by the general public in safe and efficient
      endoscopy. For this reason, reprocessing the gastrointestinal endoscope is an
      important step for effective performance of endoscopy. Disinfectants are
      essential to the endoscope reprocessing procedure. Before selecting an
      appropriate disinfectant, their characteristics, limitations and means of use
      must be fully understood. Herein, we review the characteristics of several
      currently available disinfectants, including their uses, potency, advantages, and
      disadvantages. Most disinfectants can be used to reprocess gastrointestinal
      endoscopes if the manufacturer's guidelines are followed. The selection and use
      of a suitable disinfectant depends on the individual circumstances of each
      endoscopy suite. 

PMID- 23964331
TI  - Evidence-based recommendations on upper gastrointestinal tract stenting: a report
      from the stent study group of the korean society of gastrointestinal endoscopy.
AB  - Endoscopic stents have evolved dramatically over the past 20 years. With the
      introduction of uncovered self-expanding metal stents in the early 1990s, they
      are primarily used to palliate symptoms of malignant obstruction in patients with
      inoperable gastrointestinal (GI) cancer. At present, stents have emerged as an
      effective, safe, and less invasive alternative for the treatment of malignant GI
      obstruction. Clinical decisions about stent placement should be made based on the
      exact understanding of the patient's condition. These recommendations based on a
      critical review of the available data and expert consensus are made for the
      purpose of providing endoscopists with information about stent placement. These
      can be helpful for management of patients with inoperable cancer or various
      nonmalignant conditions in the upper GI tract. 

PMID- 23964333
TI  - Propofol versus Midazolam for Sedation during Esophagogastroduodenoscopy in
      Children.
AB  - BACKGROUND/AIMS: To evaluate the efficacy and safety of propofol and midazolam
      for sedation during esophagogastroduodenoscopy (EGD) in children. METHODS: We
      retrospectively reviewed the hospital records of 62 children who underwent
      ambulatory diagnostic EGD during 1-year period. Data were collected from 34
      consecutive patients receiving propofol alone. Twenty-eight consecutive patients
      who received sedation with midazolam served as a comparison group. Outcome
      variables were length of procedure, time to recovery and need for additional
      supportive measures. RESULTS: There were no statistically significant differences
      between the two groups in age, weight, sex, and the length of endoscopic
      procedure. The recovery time from sedation was markedly shorter in propofol group
      (30+/-16.41 minutes) compared with midazolam group (58.89+/-17.32 minutes;
      p<0.0001). During and after the procedure the mean heart rate was increased in
      midazolam group (133.04+/-19.92 and 97.82+/-16.7) compared with propofol group
      (110.26+/-20.14 and 83.26+/-12.33; p<0.0001). There was no localized pain during
      sedative administration in midazolam group, though six patients had localized
      pain during administration of propofol (p<0.028). There was no serious major
      complication associated with any of the 62 procedures. CONCLUSIONS: Intravenous
      administered propofol provides faster recovery time and similarly safe sedation
      compared with midazolam in pediatric patients undergoing upper gastrointestinal
      endoscopy.

PMID- 23964332
TI  - Evidence-based recommendations on colorectal stenting: a report from the stent
      study group of the korean society of gastrointestinal endoscopy.
AB  - Recently, placement of self-expandable metallic stents has been used for the
      treatment of colorectal obstruction. As domestic awareness of colorectal cancer
      has increased, the number of colorectal stenting procedures performed has also
      increased. We aimed to provide evidence-based recommendations for colorectal
      stenting to aid gastroenterologists in making informed decisions regarding the
      management of patients who present with colorectal obstruction. The working group
      consisted of eight gastroenterologists who actively practice and conduct research
      in the field of colorectal stenting and are the members of the Stent Study Group
      of the Korean Society of Gastrointestinal Endoscopy. A literature search was
      conducted using the PubMed, Embase, KoreaMed, and the Cochrane Library databases
      to identify relevant articles published between January 2001 and June 2012. Based
      on the modified Delphi process, 10 recommendation statements regarding
      indications, usefulness, methodology and complications of colorectal stenting,
      and alternative treatments for malignant colorectal obstruction were determined.
      The contents will be widely distributed, and periodically revised to reflect the
      latest knowledge. These evidence-based recommendations for colorectal stenting
      will provide gastroenterologists and patients with appropriate and balanced
      information, and will improve the quality of care. 

PMID- 23964334
TI  - Ultrathin endoscope-assisted method for the management of upper gastrointestinal
      obstruction to avoid technical failure.
AB  - BACKGROUND/AIMS: Endoscopic management of upper gastrointestinal obstruction is
      safe and feasible. However, its technical and clinical success rate is about 90%,
      which is primarily due to inability to pass a guide-wire through the stricture.
      The aim of this study was to evaluate the usefulness of an ultrathin endoscope
      for correct placement of guide wire to avoid technical failure in upper
      gastrointestinal obstruction. METHODS: Retrospective assessment of ultrathin
      endoscope to traverse the stenosis of the upper gastrointestinal tract in
      technically difficult cases was performed. Technical and clinical success rates
      and immediate complications were analyzed. RESULTS: Nine cases were included in
      this study (eight cases of stent insertion and one case of balloon dilatation).
      Technical success was achieved in all of the patients (100%) and oral feeding was
      feasible in all of the cases (100%). Immediate complications, such as migration,
      perforation, and hemorrhage, did not develop in any of the cases. CONCLUSIONS:
      Ultrathin endoscope-assisted method for upper gastrointestinal obstruction is
      potentially safe and useful to avoid technical failure.

PMID- 23964335
TI  - Concordance of endoscopic ultrasonography-guided fine needle aspiration diagnosis
      with the final diagnosis in subepithelial lesions.
AB  - BACKGROUND/AIMS: In this study we aimed to determine the rate of concordance of
      endoscopic ultrasonography (EUS)-guided fine needle aspiration (FNA) diagnosis
      with the final diagnosis obtained by surgery or endoscopic resection and follow
      up in upper gastrointestinal subepithelial lesions. METHODS: We retrospectively
      studied patients with subepithelial lesions who underwent EUS at our center from
      2007 to 2011. RESULTS: We had a final diagnosis in 67 patients (mean age+/-SD,
      51.23+/-12.48 years; 23 [34.3%] female, 44 [65.6%] male). EUS-FNA was performed
      in all of the patients. On-site pathology was not performed. In nine of the
      patients, the obtained material which was obtained was insufficient. The
      cytologic examination was benign in 31 and malignant in 27 of the patients. Based
      on the final diagnosis, the EUS-FNA had a sensitivity of 96%, a specificity of
      100%, and a diagnostic yield of 85%. CONCLUSIONS: The diagnostic yield of EUS
      FNA, in the absence of the on-site cytopathologist, is feasible for the diagnosis
      of subepithelial lesions of the upper gastrointestinal system.

PMID- 23964336
TI  - Angular positioning of stent increases bowel perforation after self-expandable
      metal stent placement for malignant colorectal obstruction.
AB  - BACKGROUND/AIMS: Some factors like stent wires, balloon dilatation and use of
      guide wires seems to increase perforation after self-expandable metal stent
      (SEMS) placement, but few studies mentioned about the relationship between
      angulation of malignant stricture and perforation. The present study aimed to
      confirm that more angular positioning of stents increases perforation. METHODS:
      This study was conducted with retrospectively evaluation at Digestive Disease
      Center, CHA Bundang Medical Center, CHA University. Between January 2002 and
      August 2011, SEMS was inserted in 130 patients with malignant colorectal
      obstruction. We studied the difference in the angle of stenosis between
      perforation and non-perforation groups using fluorography images. RESULTS: SEMS
      insertion was performed in 130 cases of obstruction due to colon cancer.
      Perforation occurred in eight patients (6.2%) of them. Thirteen cases were
      excluded from the analysis due to poor fluoroscopic images. Among the eight
      patients with perforation, the mean stenosis angle was 109.9 degrees  compared to
      153.1 degrees  in the nonperforation group, indicating that the angle was more
      acute in the perforation group (p=0.016). CONCLUSIONS: This study shows that more
      angular positioning of stent increases bowel perforation after SEMS placement for
      malignant colorectal obstruction.

PMID- 23964337
TI  - Photodynamic therapy in unresectable cholangiocarcinoma: not for the uncommitted.
AB  - BACKGROUND/AIMS: Photodynamic therapy (PDT) in unresectable cholangiocarcinoma
      has been associated with improved survival. We report a single tertiary care
      center experience over the past 6 years. METHODS: Fifty-five patients with
      unresectable cholangiocarcinoma received PDT between 2004 and 2010. Plastic
      stents were placed after PDT to prevent cholangitis. RESULTS: Twenty-seven
      patients (49%) showed Bismuth type IV, 22 (41%) showed Bismuth type III, and six
      (10%) showed Bismuth type I and II. Twenty patients (37%) received chemotherapy
      and radiation therapy, five (9%) received chemotherapy only; and one (2%)
      received radiation therapy only. Mean number of PDT sessions was 1.9+/-1.5
      sessions (range, 1 to 9). Mean survival duration was 293+/-266 days (median, 190;
      range, 25 to 1,332). PDT related complications included three (5%) facial burn,
      three (5%) photosensitivity, and two (3%) rash. Kaplan-Meier analysis comparing
      the survival means of patients who received PDT and chemotherapy/radiation
      therapy (median survival 257 days; 95% confidence interval [CI], 166 to 528)
      versus who received PDT only (median survival 183 days; 95% CI, 129 to 224)
      showed no significant difference (log-rank p=0.20). CONCLUSIONS: PDT has a
      measurable impact on survival in unresectable cholangiocarcinoma but requires
      aggressive stenting posttherapy.

PMID- 23964338
TI  - Biliary-Pancreatic Endoscopic and Surgical Procedures in Patients under Dual
      Antiplatelet Therapy: A Single-Center Study.
AB  - BACKGROUND/AIMS: Dual antiplatelet therapy has to be used for at least 1 month
      after placement of bare metal coronary stents and for a minimum of 1 year after
      placement of drug eluting stents. Because of the higher risk of bleeding,
      guidelines strongly recommend to delay elective surgery until dual antiplatelet
      therapy is ended. However, no data are available regarding the bleeding risk in
      patients on combined aspirin/clopidogrel therapy undergoing surgical or high-risk
      endoscopic procedures. METHODS: We retrospectively analyzed the medical reports
      of patients on dual antiplatelet therapy, the patients who had to undergo
      emergency biliary-pancreatic surgery or endoscopic retrograde cholangiography
      with endoscopic sphincterotomy while in our unit between January 2009 and July
      2012. RESULTS: In our series, biliary-pancreatic surgical and endoscopic
      procedures were safely performed in 11 consecutive patients on dual antiplatelet
      therapy with no evidence of bleeding. CONCLUSIONS: In emergency, surgical and
      high risk endoscopic procedures may be performed in patients on dual antiplatelet
      therapy.

PMID- 23964339
TI  - A large-sized phytobezoar located on the rare site of the gastrointestinal tract.
AB  - Bezoars are concretions of undigested material and are most often observed in the
      stomach. They can occur at any site in the gastrointestinal tract; however,
      duodenal localization is very rare. We report the case of a 71-year-old male who
      had undergone subtotal gastrectomy with gastroduodenostomy and experienced severe
      epigastric discomfort, abdominal pain, and vomiting for a few days. An
      approximately 7*8 cm-sized mass was found on an abdominal computed tomography
      scan. On following endoscopy, a large bezoar was revealed in the duodenum and was
      removed using an endoscopic removal technique, assisted by a large amount of Coca
      Cola infusion. 

PMID- 23964340
TI  - Successful treatment of duodenal variceal bleeding by endoscopic clipping.
AB  - Duodenal varix bleeding is an uncommon cause of gastrointestinal bleeding in
      patients with portal hypertension but can cause severe and potentially fatal
      bleeding. However, the incidence is low and a good treatment method has not been
      well established yet. Duodenal variceal bleeding can be treated surgically or
      nonsurgically. We have successfully treated a patient with duodenal variceal
      bleeding secondary to liver cirrhosis using hemoclips to control the bleeding. 

PMID- 23964341
TI  - A case of squamous metaplasia of the stomach.
AB  - Intestinal metaplasia of the stomach is a common metaplastic lesion associated
      with chronic gastritis and mucosal atrophy. However, squamous metaplasia is a
      comparatively rare condition. On endoscopy, squamous metaplasia is usually
      observed as a whitish mucosal lesion in the lesser curvature of the cardiac
      region of the stomach. When Lugol's iodine solution is applied, the lesion stains
      brown in the same way as normal esophageal mucosa. We report a case of 79-year
      old man with a whitish flat lesion in the lesser curvature of the cardiac region
      on surveillance endoscopy after endoscopic treatment of gastric adenoma. The
      endoscopic biopsy showed stratified squamous epithelial mucosa. 

PMID- 23964342
TI  - Superior Mesenteric Artery Syndrome Diagnosed with Linear Endoscopic Ultrasound
      (with Video) in a Patient with Normal Body Mass Index.
AB  - Superior mesenteric artery (SMA) syndrome is an uncommon disease that results
      from SMA compression of the third portion of the duodenum. Patients with SMA
      syndrome present with upper gastrointestinal symptoms, such as nausea, vomiting,
      and abdominal pain. The diagnosis is usually made from an upper barium study or
      computed tomography. Typically, SMA syndrome is caused by a decreased
      aortomesenteric angle of 6 degrees  to 25 degrees . An underweight body mass
      index (BMI) is a risk factor for development of SMA syndrome. There are few
      reports of the role of linear endoscopic ultrasound (EUS) in the diagnosis of SMA
      syndrome. We report a case of SMA syndrome, with normal BMI, that was diagnosed
      with the aid of linear EUS. Although SMA syndrome is not typically within the
      scope of practice of endosonographers, it is useful to get familiar with the
      findings. 

PMID- 23964343
TI  - Endoscopic treatment of a symptomatic ileal lipoma with recurrent ileocolic
      intussusceptions by using cap-assisted colonoscopy.
AB  - A 73-year-old woman presented with intermittent abdominal pain and weight loss of
      15 kg for 2 years. Colonoscopy revealed an erythematous polypoid tumor with a
      long and wide stalk in the cecum, but with air inflation, it abruptly went away
      through the ileocecal valve (ICV). An abdominal computed tomography showed a well
      demarcated pedunculated subepithelial mass of 2.6*2.7 cm size with fat
      attenuation in the terminal ileum. It was an intussusceptum of the ileal lipoma
      through the ICV. This ileal lipoma was causing her symptoms because repeated
      ileocolic intussusceptions resulted in intermittent intestinal obstructions. In
      order to avoid surgical sequelae of ileal resection, snare polypectomy using cap
      assisted colonoscopy technique was performed within the ileum without
      complications. The histopathology report confirmed it as a subepithelial lipoma.
      After endoscopic resection of the ileal lipoma, the patient has been free of
      symptoms and was restored to the original weight. 

PMID- 23964344
TI  - Endoscopic Removal of a Proximally Migrated Metal Stent during Balloon Sweeping
      after Stent Trimming.
AB  - Placement of a self-expanding metal stent (SEMS) is an effective method for
      palliation of a malignant biliary obstruction. However, metal stents can cause
      various complications, including stent migration. Distally migrated metal stents,
      particularly covered SEMS, can be removed successfully in most cases. Stent
      trimming using argon plasma coagulation may be helpful in difficult cases despite
      conventional methods. However, no serious complications related to the trimming
      or remnant stent removal method have been reported due to the limited number of
      cases. In particular, proximal migration of a remnant fragmented metal stent
      after stent trimming followed by balloon sweeping has not been reported. We
      report an unusual case of proximal migration of a remnant metal stent during
      balloon sweeping following stent trimming by argon plasma coagulation. The
      remnant metal stent was successfully removed with rotation technique using a
      basket and revised endoscopically. 

PMID- 23964345
TI  - Image-enhanced endoscopy for diagnosis and treatment of gastrointestinal tumor.

PMID- 23964346
TI  - Circulating melanoma cells: scoping the target.

PMID- 23964347
TI  - Assessment of the Prognostic Value of Two Common Variants of BRCA1 and BRCA2
      Genes in Ovarian Cancer Patients Treated with Cisplatin and Paclitaxel: A
      Gynecologic Oncology Group Study.
AB  - PURPOSE: BRCA1/BRCA2 germline mutations appear to enhance the platinum
      sensitivity, but little is known about the prognostic relevance of polymorphisms
      in BRCA1/BRCA2 in epithelial ovarian cancer (EOC). This study evaluated whether
      common variants of BRCA1/BRCA2 are associated with progression-free survival
      (PFS) and overall survival (OS) in patients with advanced stage sporadic EOC.
      EXPERIMENTAL DESIGN: The allelic frequency of BRCA1 (2612C > T, P871L-rs799917)
      and BRCA2 (114A > C, N372H-rs144848) were determined in normal blood DNA from
      women in Gynecologic Oncology Group protocol #172 phase III trial with optimally
      resected stage III EOC treated with intraperitoneal or intravenous cisplatin and
      paclitaxel (C + P). Associations between polymorphisms and PFS or OS were
      assessed. RESULTS: Two hundred and thirty-two women were included for analyses.
      African Americans (AA) had different distributions for the two polymorphisms from
      Caucasians and others. For non-AA patients, the genotype for BRCA1 P871L was
      distributed as 38% for CC, 49% for CT, and 13% for TT. Median PFS was estimated
      to be 31, 21, and 21 months, respectively. After adjusting for cell type,
      residual disease, and chemotherapy regimen, CT/TT genotypes were associated with
      a 1.40-fold increased risk of disease progression [95% confidence interval (CI) =
      1.00-1.95, p = 0.049]. After removing seven patients with known BRCA1 germline
      mutations, the hazard ratio (HR) was 1.36 (95% CI = 0.97-1.91, p = 0.073). The
      association between BRCA1 P871L and OS was not significant (HR = 1.25, 95% CI =
      0.88-1.76, p = 0.212). Genotype distribution of BRCA2 N372H among non-AA patients
      was 50, 44, and 6% for AA, AC, and CC, respectively and there is no evidence that
      this BRCA2 polymorphism was related to PFS or OS. CONCLUSION: Polymorphisms in
      BRCA1 P871L or in BRCA2 N372H were not associated with either PFS or OS in women
      with optimally resected, stage III EOC treated with cisplatin and paclitaxel.

PMID- 23964351
TI  - Challenges in the diagnosis of enteropathy-associated T cell lymphoma.

PMID- 23964350
TI  - Role of archaea in human disease.

PMID- 23964349
TI  - Staphylococcal entertotoxins of the enterotoxin gene cluster (egcSEs) induce
      nitrous oxide- and cytokine dependent tumor cell apoptosis in a broad panel of
      human tumor cells.
AB  - The egcSEs comprise five genetically linked staphylococcal enterotoxins, SEG,
      SEI, SElM, SElN, and SElO and two pseudotoxins which constitute an operon present
      in up to 80% of Staphylococcus aureus isolates. A preparation containing these
      proteins was recently used to treat advanced lung cancer with pleural effusion.
      We investigated the hypothesis that egcSEs induce nitrous oxide (NO) and
      associated cytokine production and that these agents may be involved in
      tumoricidal effects against a broad panel of clinically relevant human tumor
      cells. Preliminary studies showed that egcSEs and SEA activated T cells (range:
      11-25%) in a concentration dependent manner. Peripheral blood mononuclear cells
      (PBMCs) stimulated with equimolar quantities of egcSEs expressed NO synthase and
      generated robust levels of nitrite (range: 200-250 MUM), a breakdown product of
      NO; this reaction was inhibited by NG-monomethyl-L-arginine (L-NMMA) (0.3 mM), an
      NO synthase antagonist. Cell free supernatants (CSFs) of all egcSE-stimulated
      PBMCs were also equally effective in inducing concentration dependent tumor cell
      apoptosis in a broad panel of human tumor cells. The latter effect was due in
      part to the generation of NO and TNF-alpha since it was significantly abolished
      by L-NMMA, anti-TNF-alpha antibodies, respectively, and a combination thereof. A
      hierarchy of tumor cell sensitivity to these CFSs was as follows: lung carcinoma
      > osteogenic sarcoma > melanoma > breast carcinoma >neuroblastoma. Notably, SEG
      induced robust activation of NO/TNFalpha-dependent tumor cell apoptosis
      comparable to the other egcSEs and SEA despite TNF-alpha and IFN-gamma levels
      that were 2 and 8 fold lower, respectively, than the other egcSEs and SEA. Thus,
      egcSEs produced by S. aureus induce NO synthase and the increased NO formation
      together with TNF-alpha appear to contribute to egcSE-mediated apoptosis against
      a broad panel of human tumor cells. 

PMID- 23964348
TI  - Research on the ecology of ticks and tick-borne pathogens--methodological
      principles and caveats.
AB  - Interest in tick-transmitted pathogens has experienced an upsurge in the past few
      decades. Routine application of tools for the detection of fragments of foreign
      DNA in ticks, together with a high degree of interest in the quantification of
      disease risk for humans, has led to a marked increase in the number of reports on
      the eco-epidemiology of tick-borne diseases. However, procedural errors continue
      to accumulate in the scientific literature, resulting in misleading information.
      For example, unreliable identification of ticks and pathogens, erroneous
      interpretations of short-term field studies, and the hasty acceptance of some
      tick species as vectors have led to ambiguities regarding the vector role of
      these arthropods. In this review, we focus on the ecological features driving the
      life cycle of ticks and the resulting effects on the eco-epidemiology of tick
      transmitted pathogens. We review the factors affecting field collections of
      ticks, and we describe the biologically and ecologically appropriate procedures
      for describing tick host-seeking activity and its correlation with environmental
      traits. We detail the climatic variables that have biological importance on ticks
      and explain how they should be properly measured and analyzed. We also provide
      evidence to critically reject the use of some environmental traits that are being
      increasingly reported as the drivers of the behavior of ticks. With the aim of
      standardization, we propose unambiguous definitions of the status of hosts and
      ticks regarding their ability to maintain and spread a given pathogen. We also
      describe laboratory procedures and standards for evaluating the vectorial
      capacity of a tick or the reservoir role of a host. This approach should provide
      a coherent framework for the reporting of research findings concerning ticks and
      tick-borne diseases. 

PMID- 23964352
TI  - Aortoduodenal fistula: not always bleeding.

PMID- 23964354
TI  - A luminescence lifetime-based capillary oxygen sensor utilizing monolithically
      integrated organic photodiodes.
AB  - A novel optical sensor device monolithically integrated on a glass capillary is
      presented. Therefore, we took advantage of the ability to fabricate organic
      optoelectronic devices on non-planar substrates. The functionality of the concept
      is demonstrated by realizing an integrated oxygen sensor based on luminescence
      decay time measurement. 

PMID- 23964355
TI  - Temperature- and flow-enhanced detection specificity of mutated DNA against the
      wild type with reporter microspheres.
AB  - Detection of mutated (MT) deoxyribonucleic acid (DNA) amongst the wild type (WT)
      requires the probe DNA (pDNA) that is complementary to the MT to discriminate the
      WT by one or two nucleotide mismatches. Traditionally this is achieved by raising
      the temperature to above the melting temperature (Tm) of the WT (TWT) but below
      that of the MT (TMT). However, a raised temperature is also accompanied by a
      weakened binding of the MT to the pDNA which can reduce the detection
      sensitivity. In this study, we investigated flow as a way to enhance MT detection
      specificity at a lower temperature. Gold-coated glass (GCG) slides immobilized
      with pDNA complementary to the target MT were placed at the center of the flow
      cell. The detection was done by flowing MT or WT at various concentrations
      followed by flowing 10(5) ml(-1) fluorescent reporter microspheres (FRMs) that
      were 6 MUm in size and coated with reporter DNA complementary to the MT or WT but
      different from the pDNA at various flow rates and temperatures. The detection of
      MT or WT was characterized by counting the FRMs captured on the GCG. Hepatitis B
      virus 1762/1764 double mutation (HBV DM) was the model MT and the TMT and TWT
      were 47  degrees C and 22  degrees C, respectively. It was shown that at room
      temperature, flow initially increased the binding of both the MT and WT at lower
      flow rates but decreased the binding at flow rates >=4 ml min(-1) due to the
      increase in the flow-induced impingement force on the FRMs to overcome the
      binding of the MT and the WT to the GCG at higher flow rates. At >=30  degrees C
      the decrease in binding of the WT with an increasing flow rate was more than that
      of the MT because 30  degrees C was above the TWT but still well below the TMT.
      As a result, the detection of MT at 30  degrees C with a flow rate of 4 ml min(
      1) was more specific than at 35  degrees C without flow. These results indicate
      that flow can diminish WT binding at a lower temperature than without flow and
      allow MT detection to occur at a lower temperature with high specificity.

PMID- 23964353
TI  - Isolated pancreatic tuberculosis mimicking inoperable pancreatic cancer: a
      diagnostic challenge resolved using endoscopic ultrasound-guided fine-needle
      aspiration.

PMID- 23964356
TI  - RT-isoPCR: nested, high multiplex mRNA amplification.
AB  - RT-isoPCR provides multiplex amplification of mRNA targets using a first-stage
      multiplex RT-PCR reaction with subsequent isothermal amplification for individual
      target loci detection. We demonstrate detection of 24 mRNA targets with high
      specificity and sensitivity without compromising sample variation or introducing
      biases between targets. 

PMID- 23964357
TI  - Separation of metalloproteins using a novel metal ion contaminant sweeping
      technique and detection of protein-bound copper by a metal ion probe in
      polyacrylamide gel electrophoresis: distribution of copper in human serum.
AB  - A polyacrylamide gel electrophoresis (PAGE)-based method has been developed,
      consisting of two types of gel electrophoresis, to obtain an accurate
      distribution of protein-bound metal ions in biological samples. First, proteins
      are separated by PAGE without the uptake of contaminant metal ions in the
      separation field and dissociation of metal ions from the proteins. This is
      followed by another PAGE for the separation and detection of protein-bound metal
      ions in small volume samples with high sensitivity in the ppt range using a
      fluorescent metal probe. The former is a new technique using blue-native (BN)
      PAGE to electrophoretically sweep all metal contaminants by employing two kinds
      of chelating agents. These agents form complexes with contaminants in the gel and
      the separation buffer solution, which migrate towards opposite pole directions,
      thus lowering the contaminants to below the ppt level during separation. This is
      termed "Metal Ion Contaminant Sweeping BN-PAGE (MICS-BN-PAGE)". After the
      separation of proteins under these first metal-free conditions, the metal ions in
      the gel fractions are eluted, followed by derivatization of copper ions into the
      metal probe complexes to be separated and determined by fluorescence detection in
      the second PAGE. In this PAGE-based method, the copper ions bound to
      ceruloplasmin and superoxide dismutase were quantitatively determined, in
      addition to the exchangeable albumin-bound copper ions. This system successfully
      provided distribution maps of protein-copper in human serum. The precise
      distribution of copper in human serum was investigated, and found to be different
      from that which is widely accepted. 

PMID- 23964358
TI  - Correlation of in vitro and in vivo plasma protein binding using
      ultracentrifugation and UPLC-tandem mass spectrometry.
AB  - The aim of the present study is to develop and demonstrate the correlation
      between in vitro and in vivo Plasma Protein Binding (PPB) using the
      ultracentrifugation method for its validation by using marketed compounds like
      atenolol, theophylline and phenytoin. In this study, in vitro PPB is carried out
      using ultracentrifugation, by spiking the selected marketed compounds at
      concentrations of 5 and 15 MUM in plasma. In an in vivo study, rats (n = 3) were
      given a single oral dose (10 mg kg(-1)) and post-dose samples were subjected to
      ultracentrifugation to obtain the protein-free fraction. A rapid and highly
      sensitive method was developed and validated for determining the free fraction of
      marketed compounds in rat plasma using protein precipitation and analysis using
      an ultra performance liquid chromatography electrospray ionization (ESI) tandem
      mass spectrometer system (UPLC-MS/MS). The in vitro free fraction (fup) values
      were 0.93 +/- 0.07 for atenolol, 0.31 +/- 0.03 for theophylline and 0.09 +/- 0.02
      for phenytoin which correlated well with the corresponding in vivo values of 0.91
      +/- 0.03 for atenolol, 0.25 +/- 0.02 for theophylline and 0.09 +/- 0.01 for
      phenytoin with a coefficient of variation less than 11.06%, 11.45% and 13.67%,
      respectively. Therefore the validated high-throughput in vitro PPB study is
      expected to have a powerful impact on reducing the cost as well as time in the
      drug discovery process. 

PMID- 23964359
TI  - Ultrasensitive detection of small molecule-protein interaction via terminal
      protection of small molecule linked DNA and Exo III-aided DNA recycling
      amplification.
AB  - Terminal protection of small molecule linked DNA assays amplified by Exo III
      aided DNA recycling is developed for the detection of streptavidin-biotin
      interaction, with a detection limit of 0.8 fM streptavidin in the "turn-on"
      state, indicating that the proposed method is an ultrasensitive platform for the
      detection of small molecule-protein interactions. 

PMID- 23964360
TI  - Hydrogen storage: beyond conventional methods.
AB  - The efficient storage of hydrogen is one of three major hurdles towards a
      potential hydrogen economy. This report begins with conventional storage methods
      for hydrogen and broadly covers new technology, ranging from physical media
      involving solid adsorbents, to chemical materials including metal hydrides,
      ammonia borane and liquid precursors such as alcohols and formic acid. 

PMID- 23964361
TI  - A reproducible mechano-responsive luminescent system based on a discotic crown
      ether derivative doped with fluorophores: taking advantage of the phase
      transition of a matrix.
AB  - A reproducible mechano-responsive luminescent system based on a discotic crown
      ether derivative (1) doped with a small amount of fluorophore has been prepared.
      The emission intensity was enhanced when the material was subjected to mechanical
      shear with localized response.

PMID- 23964362
TI  - Direct observation of valence band splitting using room temperature
      photoluminescence of CdS hollow submicrospheres.
AB  - The room-temperature photoluminescence spectra of CdS hollow submicrospheres
      prepared via employing silica hard templates and microwave irradiation present a
      profound insight into the quantum confinement-induced splitting of electron and
      hole states in the valence band. 

PMID- 23964363
TI  - beta-Turn structure in glycinylphenylalanine dipeptide based N-amidothioureas.
AB  - Transforming the C-terminal amide of a glycinylphenylalanine dipeptide into N
      amidothiourea affords a beta-turn structure in the formed dipeptide based N
      amidothioureas, which can be readily identified by an induced CD signal from the
      achiral phenylthiourea chromophore. 

PMID- 23964364
TI  - Photoreversible switching between assembly and disassembly of a supramolecular
      polymer involving an azobenzene-bridged pillar[5]arene dimer.
AB  - We report a photo-reversible switching system between assembly and disassembly of
      a supramolecular polymer consisting of an azobenzene-bridged pillar[5]arene
      dimer. 

PMID- 23964366
TI  - Ensuring safe use of medical devices.

PMID- 23964365
TI  - Karl Holubar (1936-2013): dermatologic historian par excellence.

PMID- 23964367
TI  - New recommended practices for sharps safety released.

PMID- 23964368
TI  - Perioperative nurse super users for EHR implementation.

PMID- 23964369
TI  - Evidence appraisal of Cosetto DJ, Goudar A, Parkinson K. Safety of peri-operative
      low-dose aspirin as a part of multimodal venous thromboembolic prophylaxis for
      total knee and hip arthroplasty. J Orthop Surg (Hong Kong). 2012;20(3):341-343.

PMID- 23964370
TI  - Authors' reply.

PMID- 23964371
TI  - Hematology.

PMID- 23964373
TI  - Letter from the new editor.

PMID- 23964372
TI  - Letter from the editor emeritus.

PMID- 23964374
TI  - Seeing further than your nose.
AB  - Among monocular depth cues, ocular parallax (first described formally by Brewster
      in 1844) remains mostly unknown, its role in perception still not investigated
      scientifically. Given that every single eye movement induces ocular parallax, it
      is a potentially useful depth cue. This paper is an attempt to revive interest in
      the topic. As a monocular depth cue, ocular parallax naturally leads us to
      consider its benefit for a monocularly enucleated individual. Throughout history,
      numerous illustrious personalities coped with this fate in various ways. Here, we
      consider some historical insights into the visual life of the erstwhile duke of
      Urbino, Federico da Montefeltro (1422-1482), warlord and patron to the painter
      Piero della Francesca, and the Japanese warlord, Masamune Date (1567-1636), a
      vocal patron of exploration and the arts.

PMID- 23964375
TI  - Face contour is crucial to the fat face illusion.
AB  - In 2010 Thompson reported a "fat face thin" illusion that, when next to an
      inverted face, an upright face looks "fatter". Sun et al (2012 Perception 41 117
      120) observed that one of the faces need not be inverted for the illusion to
      emerge: when two identical faces are presented one above the other, the face at
      the bottom appears "fatter" than the top one. Neither inverted faces nor clocks
      induced the illusion. Here we conducted three experiments probing the role that
      face contour plays in producing the fat face illusion. In experiment 1 line
      drawing faces were found to induce the illusion, suggesting that face contour is
      important for producing the illusion. In experiment 2 line drawing faces with
      scrambled internal features and empty line drawing faces devoid of internal
      features were found to induce the illusion. In experiment 3 internal face
      features arranged in their canonical face layout, but not in a scrambled layout,
      were found to induce the illusion. However, the magnitude of the effect was
      significantly weaker than the effect obtained for empty face contour in
      experiment 2. Collectively, these results suggest that a fat face illusion is
      obtained when there is sufficient information in the stimulus to activate an
      internal face schema.

PMID- 23964376
TI  - The effect of head turn and illumination on the perceived direction of gaze.
AB  - Thirty observers judged the direction of monocular and binocular gaze from a
      model's LCD-imaged head when the head, gaze, and illumination were either
      straight or turned 20.6 degrees to the side. The judged direction of binocular
      eye contact from a turned head was judged to go past the direction of the
      observer, while judged monocular gaze from the eye toward the observer followed
      that for binocular gaze. Although judged monocular gaze from the eye away from
      the observer also passed the observer, it did so by a smaller amount. The judged
      direction of binocular gaze in the same direction as the head turn was judged to
      pass the direction of the head turn. The judged direction of monocular gaze from
      the eye away from the observer was nearly true, but the judged direction of
      monocular gaze from the eye toward the observer was judged as closer to the
      observer than true. Illumination of the model's head from the side made the
      direction of both head turn and gaze appear to move away from the direction of
      the light source. These results are discussed in connection with angle k and the
      perceived direction of head turn.

PMID- 23964377
TI  - Perceiving space and optical cues via a visuo-tactile sensory substitution
      system: a methodological approach for training of blind subjects for navigation.
AB  - A methodological approach to perceptual learning was used to allow both early
      blind subjects (experimental group) and blindfolded sighted subjects (control
      group) to experience optical information and spatial phenomena, on the basis of
      visuo-tactile information transmitted by a 64-taxel pneumatic sensory
      substitution device. The learning process allowed the subjects to develop
      abilities in spatial localisation, shape recognition (with generalisation to
      different points of view), and monocular depth cue interpretation. During the
      training phase, early blind people initially experienced more difficulties than
      blindfolded sighted subjects (having previous perceptual experience of
      perspective) with interpreting and using monocular depth cues. The amelioration
      of the performance for all blind subjects during training sessions and the quite
      similar level of performance reached by two groups in the final navigation tasks
      suggested that early blind people were able to develop and apply cognitive
      understanding of depth cues. Both groups showed generalisation of the learning
      from the initial phases to cue identification in the maze, and subjectively
      experienced shapes facing them. Subjects' performance depended not only on their
      perceptual experience but also on their previous spatial competencies.

PMID- 23964378
TI  - Effects of additional visual oscillation on vection under voluntary eye movement
      conditions--retinal image motion is critical in vection facilitation.
AB  - Horizontal oscillation introduced into a visual inducer can enhance an observer's
      illusory perception of vertical self-motion induced by a vertically moving optic
      flow pattern. To examine the effects of increased retinal image motion on the
      facilitation of vection, vection strength was analysed under various stimulus
      conditions where the oscillation of the retinal image was determined both by the
      motion of the visual stimulus and the observer's eye movements. The results
      indicated that the facilitation of vection was regulated by the oscillation of
      the visual stimulus on the observer's retina rather than the stimulus oscillation
      per se. Thus, the current experiment clearly favours the hypothesis that
      increased retinal image motion plays a critical role in the facilitation of
      vection.

PMID- 23964379
TI  - Responses contribute to context effects on ratio-setting timing tasks.
AB  - Short durations in a range of standard durations are typically overreproduced and
      long durations underreproduced ('Vierordt's Law'). This contextual distortion may
      result from each trial assimilating the central tendency of the preceding series.
      We examine whether responses as well as standard durations contribute to this
      distortion. Two experiments using nonequal-setting ratio tasks are described. On
      equal-setting ratio tasks the means of the standards and responses are nearly
      equal, but in half-setting and double-setting standards and responses differ. In
      both experiments a central tendency of standards plus responses better predicted
      the indifference interval than did the mean of the standards alone. The
      coefficients of variation were larger for all double-setting conditions than for
      half-setting at the same response durations, suggesting pooling of the trial
      variance with the central tendency's variance. Longer equal-setting reproductions
      were generated by randomly intermixing equal-setting with double-setting than by
      intermixing with half-setting. Thus, assimilation of a central tendency that
      includes both standards and responses can account for the location of the
      indifference intervals ('Vierordt's Law'), for the response variation and for the
      additive effect we observed where two entire response curves (for equal-setting)
      were shifted relative to each other by the influence of nonequal-setting trials.

PMID- 23964380
TI  - Space and time: an impact of spatial separation, apparent motion, and perceptual
      grouping on TOJ performance.
AB  - This study explored the effects of spacing and objecthood (ie grouping based on
      closure) on temporal order judgment (TOJ) with displays that either involved
      successive onset of the target stimuli, resulting in apparent motion (experiments
      1 and 2), or included simultaneous onset but successive shortening of the
      stimuli, and therefore did not result in apparent motion (experiment 3). We found
      a robust effect of spatial separation whose nature depended on whether or not the
      display allowed the emergence of illusory motion. Specifically, with apparent
      motion TOJ was best with the smallest spacing, but without it TOJ was worst with
      the smallest spacing. Moreover, overall accuracy was better with, than without,
      apparent motion. A small effect of objecthood--poorer TOJ performance when the
      elements formed an object--emerged only when spacing was not manipulated. These
      findings suggest that different mechanisms mediate temporal processing when we
      have access to motion information than when we do not.

PMID- 23964381
TI  - Vection in depth during treadmill walking.
AB  - Vection has typically been induced in stationary observers (ie conditions
      providing visual-only information about self-motion). Two recent studies have
      examined vection during active treadmill walking--one reported that treadmill
      walking in the same direction as the visually simulated self-motion impaired
      vection (Onimaru et al, 2010 Journal of Vision 10(7):860), the other reported
      that it enhanced vection (Seno et al, 2011 Perception 40 747-750; Seno et al,
      2011 Attention, Perception, & Psychophysics 73 1467-1476). Our study expands on
      these earlier investigations of vection during observer active movement. In
      experiment 1 we presented radially expanding optic flow and compared the vection
      produced in stationary observers with that produced during walking forward on a
      treadmill at a 'matched' speed. Experiment 2 compared the vection induced by
      forward treadmill walking while viewing expanding or contracting optic flow with
      that induced by viewing playbacks of these same displays while stationary. In
      both experiments subjects' tracked head movements were either incorporated into
      the self-motion displays (as simulated viewpoint jitter) or simply ignored. We
      found that treadmill walking always reduced vection (compared with stationary
      viewing conditions) and that simulated viewpoint jitter always increased vection
      (compared with constant velocity displays). These findings suggest that while
      consistent visual-vestibular information about self-acceleration increases
      vection, biomechanical self-motion information reduces this experience
      (irrespective of whether it is consistent or not with the visual input).

PMID- 23964382
TI  - Simple 3-D stimulus for motion parallax and its simulation.
AB  - Simulation of a given stimulus situation should produce the same perception as
      the original. Rogers et al (2009 Perception 38 907-911) simulated Wheeler's
      (1982, PhD thesis, Rutgers University, NJ) motion parallax stimulus and obtained
      quite different perceptions. Wheeler's observers were unable to reliably report
      the correct direction of depth, whereas Rogers's were. With three experiments we
      explored the possible reasons for the discrepancy. Our results suggest that
      Rogers was able to see depth from the simulation partly due to his experience
      seeing depth with random dot surfaces.

PMID- 23964383
TI  - Alcohol consumption enhances vection.
AB  - We assessed changes in forward vection following alcohol consumption, and found
      that alcohol consumption enhanced vection. This result indicates that alcohol can
      affect psychophysical processes responsible for self-motion perception.

PMID- 23964384
TI  - Walking through apertures: do you know what you are doing during body-scaled
      action?
AB  - We investigated whether body-scaled action is influenced by awareness of task
      performance. Participants walked through apertures varying in size. Awareness of
      performing the action was manipulated by asking half of the participants to
      concurrently perform a haptic memory task. Distracted participants showed a
      smaller maximum amount of shoulder rotation at A/S(crit). Walking through
      apertures thus seems a rather automatic/uniform process regarding action
      planning, but being distracted from performing the action appears to influence
      how the action is performed, and may increase its efficiency.

PMID- 23964385
TI  - Effects of breastfeeding on weight loss and recovery of pregestational weight in
      adolescent and adult mothers.
AB  - BACKGROUND: Exclusive breastfeeding (EBF) in adolescent mothers has been
      associated with greater postpartum maternal weight loss. OBJECTIVE: To assess the
      associations between EBF and weight loss in adolescent and adult mothers and
      between EBF and weight and length gain of their children. METHODS: A cohort of 68
      adolescent mothers (15 to 19 years), 64 adult mothers (20 to 29 years), and their
      infants were studied. Anthropometric measurements were performed at 15, 90, 180,
      and 365 days postpartum in the mothers and children. EBF was defined as
      consumption of human milk without supplementation of any type (water, juice,
      nonhuman milk, or food) for 4 months. RESULTS: Sixty-five percent of mothers
      sustained EBF for 4 months. There were no significant differences in the weight
      or length of the infants of adolescent and adult mothers at 365 days postpartum.
      Among infants of adult mothers, there was a significant difference between the
      weight gain of those were exclusively breastfed and those who were not
      exclusively breastfed (6,498 +/- 1,060 vs 6,096 +/- 1,035 g, p < .050) at 365
      days postpartum, according to the parameters for weight gain and length
      established by the World Health Organization (WHO). Among both adult and
      adolescent mothers, those who practiced EBF lost more weight than those who did
      not practice EBF (-2.9 kg, 95% interquartile range, -5.7 to 0.8 kg, vs -1.8 kg
      95% interquartile range -2.8 to 2.2 kg; p = .004). Gestational weight gain,
      duration of EBF, and recovery menstruation explained 21% of the variance (F =
      28.184, p = .001) in change in postpartum maternal weight (in kilograms) from 0
      to 365 days postpartum in all mothers. Pregestational weight, duration of EBF,
      and maternal age were factors that explained 14% (F = 22.759, p = .001) of the
      change in the weight and length of the infants from 0 to 365 days of life.
      CONCLUSIONS: EBF in adolescent and adult mothers influences postpartum weight
      loss and provides adequate infant growth in accordance with the WHO 2006
      standards.

PMID- 23964386
TI  - The importance of using food and nutrient intake data to identify appropriate
      vehicles and estimate potential benefits of food fortification in Uganda.
AB  - BACKGROUND: Concern over micronutrient inadequacies in Uganda has prompted the
      introduction of mass fortification. OBJECTIVE: To use food intake to determine
      nutrient inadequacies in children aged 24 to 59 months and nonpregnant women of
      reproductive age, and to model the adequacy of mass fortification. METHODS: Data
      were collected by the 24-hour recall method in three regions. Usual nutrient
      intakes were calculated by adjusting actual intake distribution for the
      intraindividual variance. The impact of fortification on intake adequacy was
      simulated. RESULTS: The nutrients with the highest prevalence of inadequate
      intake across regions were vitamin A (30% to 99%), vitamin B12 (32% to 100%),
      iron (55% to 89%), zinc (18% to 82%), and calcium (84% to 100%). According to
      simulations, fortification of vegetable oil and sugar with vitamin A would reduce
      the prevalence of vitamin A inadequacy in the Western and Northern regions; in
      Kampala it would eliminate vitamin A inadequacy but would cause 2% to 48% of
      children to exceed the Tolerable Upper Intake Level (UL). The proposed
      fortification of wheat flour would reduce the prevalence of inadequate intakes of
      thiamine, riboflavin, folate, and niacin in Kampala, but would have little impact
      in the other two regions due to low flour consumption. CONCLUSIONS: Micronutrient
      fortification of vegetable oil and sugar in all regions and of wheat flour in
      Kampala would reduce the prevalence of micronutrient inadequacies. However, the
      wheat flour formulation should be modified to better meet requirements, and the
      vitamin A content in sugar should be reduced to minimize the risk of high
      intakes. Maize flour may be suitable for targeted fortification, but prior
      consolidation of the industry would be required for maize flour to become a good
      vehicle for mass fortification.

PMID- 23964388
TI  - Low vitamin B12 intake during pregnancy and lactation and low breastmilk vitamin
      12 content in rural Kenyan women consuming predominantly maize diets.
AB  - BACKGROUND: Vitamin B12 deficiency during pregnancy and lactation may negatively
      affect fetal growth, brain development, pregnancy outcome, and breastmilk vitamin
      B12 content. OBJECTIVE: To examine associations between pregnant and lactating
      women's vitamin B12 intake and pregnancy outcomes, breastmilk vitamin B12
      concentration, and growth and development of breastfed infants from birth to 6
      months. METHODS: One hundred thirty-eight Kenyan women were followed during
      pregnancy, with 98 followed through 6 months of lactation and providing 294
      randomly collected breastmilk samples. Maternal hematologic analyses were
      performed for erythrocyte morphology, erythrocyte size, and serum vitamin B12
      concentration. Women's and infants'food intake was assessed. Breastmilk vitamin
      B12 was measured by a competitive binding isotope dilution technique. Infant
      anthropometric data and the Brazelton Neonatal Behavioral Assessment Scale
      (BNBAS) were assessed within 3 days after birth. The Infant Bayley Motor Scale
      was assessed at 6 months. Statistical analyses included simple regression and
      correlation analyses in relation to vitamin B12 status and gestational age.
      RESULTS: Intrauterine growth restriction and stillbirths were correlated with
      maternal macrocytic anemia and hypersegmented polymorphonuclear nuclei.
      Postpartum maternal vitamin B12 intake influenced breastmilk vitamin B12 levels 1
      to 6 months postpartum. No associations were found between vitamin B12 intake
      during pregnancy or vitamin B12 levels in breastmilk and infant length, weight,
      or head circumference at birth or 6 months. Vitamin B12 intake during pregnancy
      was correlated with improved scores on infants' BNBAS reflex subscale (R = -0.19,
      p = .05) with adjustment for gestational age. Bayley Motor Scale results at 6
      months were not significantly associated with breastmilk or supplemental feeding
      vitamin B12 content. CONCLUSIONS: Vitamin B12 deficiency may adversely affect
      pregnancy outcome, infant reflexes at birth, and breastmilk vitamin B12 content.

PMID- 23964387
TI  - Associations among dietary zinc intakes and biomarkers of zinc status before and
      after a zinc supplementation program in Guatemalan schoolchildren.
AB  - BACKGROUND: The associations among dietary zinc intakes and biomarkers of zinc
      status are unknown in apparently healthy children at high risk for zinc
      deficiency. OBJECTIVE: To assess associations among zinc-related parameters in a
      sample of Guatemalan school-aged children. METHODS: We assessed total dietary
      intakes and biomarkers of zinc status before and after receiving 6 months of zinc
      supplementation or placebo in 691 Guatemalan schoolchildren aged 6 to 11 years.
      Most of the children also received zinc-fortified milk from a government program
      that started shortly after the trial began. We assessed associations between zinc
      intakes and serum zinc, alkaline phosphatase (ALP), and albumin. RESULTS: At
      baseline, the prevalence of serum zinc < 65 microg/dL and dietary zinc intake
      below Estimated Average Requirements (EAR) (< 4 and < 7 mg/day for children < 9
      and > or = 9 years, respectively) were 21.6% and 39.4%, respectively. Pearson
      correlations between serum zinc concentration and dietary zinc intake, serum ALP,
      and serum albumin were r = 0.07, 0.15, and 0.07, respectively. At the 6-month
      follow-up, low serum zinc and low total (diet plus fortified milk) zinc intakes
      were observed in 1.2% and 0.0% of children in the zinc-supplemented group and
      4.0% and 34.1% in the placebo group, respectively. Pearson correlations between
      serum zinc concentration and total zinc intake, serum ALP, and serum albumin were
      0.10, 0.06, and -0.11 in the zinc-supplemented group and -0.04, 0.05, and 0.01 in
      the placebo group, respectively. CONCLUSIONS: Zinc intake was inconsistently
      associated with markers of serum zinc concentration. Zinc fortification or
      supplementation attenuated the associations.

PMID- 23964389
TI  - Estimates of exclusive breastfeeding rates among mother-infant dyads in
      Quetzaltenango, Guatemala, vary according to interview method and time frame.
AB  - BACKGROUND: The World Health Organization (WHO) recommends exclusive
      breastfeeding, defined as receiving only breastmilk, through the first 6 months
      of life to optimize survival, health, and development. OBJECTIVE: To assess
      exclusive and predominant breastfeeding rates, as defined by WHO, in a sample of
      Guatemalan infants using three dietary assessment methods. METHODS: Mothers of
      156 infants (78 boys and 78 girls) in the 6th month of life, attending a public
      health center in Quetzaltenango, an urban area located in the Highlands of
      Guatemala, were recruited. A single face-to-face interview was performed to
      assess infant dietary intake using three methods: previous day dietary recall (as
      suggested by WHO), current feeding practices, and recall of feeding practices
      since birth. RESULTS: Based on the previous day dietary recall method, exclusive
      breastfeeding was reported by 87 (56%) of the mothers. Exclusive breastfeeding
      rates were much lower when estimated by current feeding practices questions (20%)
      and even lower when based on recall of feeding practices since birth (9%). The
      sum of exclusive and predominant breastfeeding (full breastfeeding) rates was
      58%, 49%, and 31% based on previous day dietary recall, current feeding
      practices, and recall of feeding practices since birth, respectively.
      CONCLUSIONS: The WHO method of dietary assessment, based solely on the previous
      day dietary recall, overestimates the exclusive breastfeeding rate compared with
      recall of feeding practices since birth. In our population sample, adherence to
      the WHO guidelines for feeding in the first semester of infancy was less than
      ideal and in need of strengthening.

PMID- 23964390
TI  - Using program impact pathways to understand and improve program delivery,
      utilization, and potential for impact of Helen Keller International's homestead
      food production program in Cambodia.
AB  - BACKGROUND: Evidence of the impact of homestead food production programs on
      nutrition outcomes such as anemia and growth is scant. In the absence of
      information on program impact pathways, it is difficult to understand why these
      programs, which have been successful in increasing intake of micronutrient-rich
      foods, have had such limited documented impact on nutrition outcomes. OBJECTIVE:
      To conduct a process evaluation of Helen Keller International's (HKI's) homestead
      food production program in Cambodia to assess whether the program was operating
      as planned (in terms of design, delivery, and utilization) and to identify ways
      in which the program might need to be strengthened in order to increase its
      potential for impact. METHODS: A program theory framework, which laid out the
      primary components along the hypothesized program impact pathways, was developed
      in collaboration with HKI and used to design the research. Semistructured
      interviews and focus group discussions with program beneficiaries (n = 36 and 12,
      respectively), nonbeneficiaries (n = 12), and program implementers (n = 17 and 2,
      respectively) and observations of key program delivery points, including health
      and nutrition training sessions (n = 6), village model farms (n = 6), and
      household gardens of beneficiaries (n = 36) and nonbeneficiaries (n = 12), were
      conducted to assess the delivery and utilization of the primary program
      components along the impact pathways. RESULTS: The majority of program components
      were being delivered and utilized as planned. However, challenges with some of
      the key components posited to improve outcomes such as anemia and growth were
      noted. Among these were a gap in the expected pathway from poultry production to
      increased intake of eggs and poultry meat, and some weaknesses in the delivery of
      the health and nutrition training sessions and related improvements in knowledge
      among the village health volunteers and beneficiaries. CONCLUSIONS: Although the
      program has been successful in delivering the majority of the program components
      as planned and has documented achievements in improving household production and
      intake of micronutrient-rich foods, it is likely that strengthening delivery and
      increasing utilization of some program components would increase its potential
      for nutritional impacts. This research has highlighted the importance of
      designing a program theory framework and assessing the components that lie along
      the primary program impact pathways to optimize program service delivery and
      utilization and, in turn, potential for impact.

PMID- 23964391
TI  - Differences in circulating non-transferrin-bound iron after oral administration
      of ferrous sulfate, sodium iron EDTA, or iron polymaltose in women with marginal
      iron stores.
AB  - BACKGROUND: The adverse interactions between iron supplements and malaria have
      driven the assessment of new therapeutic options for anemia prophylaxis in areas
      holoendemic for falciparum malaria. OBJECTIVE: To determine the responses of
      circulating non-transferrin-bound iron (NTBI) and plasma iron to three different
      oral iron compounds--ferrous sulfate, sodium iron ethylenediaminetetraacetate
      (NaFeEDTA), and iron polymaltose (IPM)--in women with marginal iron stores.
      METHODS: Serum samples from 10 Guatemalan women with marginal iron stores were
      collected every 90 minutes over a period of 270 minutes, after the individually
      randomized administration of 100 mg of iron from each of the three studied iron
      compounds or water alone. Serum iron concentration was quantified by the
      ferrozine method, and circulating NTBI concentration was determined with a
      fluorometric competitive binding assay. Kinetic responses and maximal cumulative
      changes in serum concentrations of iron and NTBI were compared between the four
      treatments. Comparison was made with data from the same protocol in iron-adequate
      men. RESULTS: The serum iron and NTBI responses to ferrous sulfate were
      significantly greater than those to water and the other two iron compounds. Serum
      iron responses to IPM did not differ from those to water alone. CONCLUSIONS: The
      administration of the two "slow-release" iron compounds, NaFeEDTA and IPM,
      resulted in a highly significant suppression of the appearance of NTBI in the
      circulation in the postsupplement period. These two bioavailable forms of iron
      supplement could represent a safe option for supplementation in malarial areas.
      The slope of the iron-NTBI relationship is steeper in men than in women.

PMID- 23964392
TI  - Commentary: The changing focus for improving nutrition.

PMID- 23964393
TI  - Comparison of the estimated cost-effectiveness of preventive and therapeutic zinc
      supplementation strategies for reducing child morbidity and mortality in sub
      Saharan Africa.
AB  - BACKGROUND: Zinc supplementation of young children in lower-income countries
      reduces morbidity from diarrhea and pneumonia and all-cause mortality, but the
      most cost-effective approach for distributing zinc supplements is unknown.
      OBJECTIVE: To examine the potential impact of four possible strategies for
      delivering zinc supplements on disease prevention and deaths averted among
      children 6 to 59 months of age in sub-Saharan Africa. METHODS: We analyzed
      different zinc supplementation strategies to assess their likely impact on
      morbidity and mortality of preschool children in sub-Saharan Africa and to
      estimate their possible costs. RESULTS: Preventive zinc supplementation reduces
      diarrhea incidence by 27% among children 12 to 59 months of age, pneumonia
      incidence by 21% among children 6 to 59 months of age, and all-cause mortality by
      18% among children 12 to 59 months of age. The likely average total program costs
      of zinc supplementation programs were estimated from the outlays of existing
      service delivery platforms, such as child health days, community-based nutrition
      programs, and clinic-based treatment of diarrhea, assuming different levels of
      coverage and target age ranges of children. CONCLUSIONS: We found that the
      average total costs per life saved ranged from approximately US$462 to US$3,111,
      and the most cost-effective interventions were weekly or intermittent preventive
      zinc supplementation, because of the possibility of high coverage and fewer
      supplements required. Empirical data from zinc supplementation programs will be
      needed to confirm these estimates.

PMID- 23964394
TI  - Zinc as a potential coadjuvant in therapy for type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes is highly prevalent in populations having high rates
      of overweight and obesity. It is a chronic condition responsible for long-term
      severe dysfunction of several organs, including the kidneys, heart, blood
      vessels, and eyes. Although there are a number of pharmacologic products in the
      market to treat insulin resistance and impaired insulin secretion--the most
      prominent features of this disease--interventions directed at preserving the
      integrity and function of beta-cells in the long term are less available. The use
      of some nutrients with important cellular protective roles that may lead to a
      preservation of beta-cells has not been fully tested; among these, zinc may be an
      interesting candidate. OBJECTIVE: To assess the potential of zinc supplementation
      as coadjuvant to diabetes therapy. METHODS: This article reviews the available
      information on the use of zinc as part of diabetes therapy. RESULTS: Cellular and
      animal models provide information on the insulin mimetic action of zinc, as well
      as its role as a regulator of oxidative stress, inflammation, apoptosis, and
      insulin secretion. Zinc supplementation studies in humans are limited, although
      some positive effects have been reported; mainly, a modest but significant
      reduction in fasting glucose and a trend to decreased glycated hemoglobin
      (HbA1c). CONCLUSIONS: Zinc supplementation may have beneficial effects on
      glycemic control. Nevertheless, among the studies considered, the vast majority
      lasted for 6 months or less, suggesting the importance of conducting long
      duration studies given the characteristics of type 2 diabetes as a chronic
      disease.

PMID- 23964395
TI  - Protein Quality Workshop: importance of protein quality in prevention and
      treatment of child malnutrition.

PMID- 23964396
TI  - Protein Quality Workshop.

PMID- 23964397
TI  - Keynote: rethinking protein.

PMID- 23964398
TI  - Overview of changing protein and amino acid requirements and application to
      pregnancy requirements.

PMID- 23964399
TI  - Methodology for evaluating protein quality and implications of requirements for
      product fortification.

PMID- 23964400
TI  - Meeting protein needs at 6 to 24 months of age.

PMID- 23964401
TI  - Assessment of protein adequacy in developing countries: quality matters.

PMID- 23964402
TI  - Inadequate dietary protein intake: when does it occur and what are the
      consequences?

PMID- 23964403
TI  - Cow's milk in the prevention and treatment of stunting and wasting.

PMID- 23964404
TI  - Effects of soy infant formula on growth and development in the first year of
      life.

PMID- 23964405
TI  - Protein source and quality in therapeutic foods affect the immune response and
      outcome in severe acute malnutrition.

PMID- 23964406
TI  - Improving linear growth without excess body fat gain in women and children.

PMID- 23964407
TI  - Comparing the value of protein sources for maternal and child nutrition.

PMID- 23964408
TI  - Effect of protein intake from 6 to 24 months on insulin-like growth factor 1 (IGF
      1) levels, body composition, linear growth velocity, and linear growth
      acceleration: what are the implications for stunting and wasting?

PMID- 23964409
TI  - Digestibility issues of vegetable versus animal proteins: protein and amino acid
      requirements--functional aspects.

PMID- 23964410
TI  - Arginine production during pregnancy: a study of Jamaican, Indian, and American
      women.

PMID- 23964411
TI  - Discussion by workshop participants: summary of presentations, remaining
      knowledge gaps, and research needs.

PMID- 23964412
TI  - Supporting interruption management and multimodal interface design: three meta
      analyses of task performance as a function of interrupting task modality.
AB  - OBJECTIVE: The aim of this study was to integrate empirical data showing the
      effects of interrupting task modality on the performance of an ongoing visual
      manual task and the interrupting task itself. The goal is to support interruption
      management and the design of multimodal interfaces. BACKGROUND: Multimodal
      interfaces have been proposed as a promising means to support interruption
      management.To ensure the effectiveness of this approach, their design needs to be
      based on an analysis of empirical data concerning the effectiveness of individual
      and redundant channels of information presentation. METHOD: Three meta-analyses
      were conducted to contrast performance on an ongoing visual task and interrupting
      tasks as a function of interrupting task modality (auditory vs. tactile, auditory
      vs. visual, and single modality vs. redundant auditory-visual). In total, 68
      studies were included and six moderator variables were considered. RESULTS: The
      main findings from the meta-analyses are that response times are faster for
      tactile interrupting tasks in case of low-urgency messages.Accuracy is higher
      with tactile interrupting tasks for low-complexity signals but higher with
      auditory interrupting tasks for high-complexity signals. Redundant auditory
      visual combinations are preferable for communication tasks during high workload
      and with a small visual angle of separation. CONCLUSION: The three meta-analyses
      contribute to the knowledge base in multimodal information processing and design.
      They highlight the importance of moderator variables in predicting the effects of
      interruption task modality on ongoing and interrupting task performance.
      APPLICATIONS: The findings from this research will help inform the design of
      multimodal interfaces in data-rich, event-driven domains.

PMID- 23964413
TI  - An online means of testing asymmetries in seating preference reveals a bias for
      airplanes and theaters.
AB  - OBJECTIVE: The aim of this study was to investigate asymmetrical interactions
      between humans and their environment using online seat booking sites. BACKGROUND:
      Functional differences between the cerebral hemispheres affect the choices people
      make. For example, when asked to imagine going to a cinema, people preferentially
      select seats to the right We investigated whether this experimental research
      generalizes to online booking sites for aircraft and theaters. METHOD: Occupancy
      rates for seats taken on the left and right sides were assessed for 100 airline
      flights with 12,762 available seats and 37 theater performances with 34,456
      seats. On the basis of previous research, a rightward bias was predicted for
      aircraft and theaters. RESULTS: For aircraft, contrary to expectation, occupancy
      rate was higher for left- compared with right-side seats. For theaters, a
      rightward bias was observed when the theater was less than half full.The bias was
      not affected by the orientation of the map. CONCLUSION: For aircraft, the
      leftward preference could be attributable to a rightward turning bias or a
      "feeling" that the port seats are closer to the exit, even though they are not.
      For theaters, the data demonstrate that the rightward preference observed in
      earlier studies exists only when the theater is relatively empty. APPLICATION:
      Asymmetrical seating may play an important role in the efficient assimilation of
      information from the environment, and this role should take this into account
      when designing effective human-environment interfaces.The online method of
      assessing seating used in the current study provides an informative and
      potentially powerful means of assessing asymmetries in human perception and
      action.

PMID- 23964414
TI  - Stopping decisions: information order effects on nonfocal evaluations.
AB  - OBJECTIVE: We investigated how the order in which information is presented
      affects when a person decides to stop performing a task. BACKGROUND: A stopping
      decision is a decision to stop performing a task on the basis of a sequence of
      cues. Previous order-effects models do not account for how these contexts limit
      available working memory for making such decisions. METHOD: Participants decided
      how long to perform a task known as the Work Hazard Game that began by rewarding
      points but later cost points if work continued after an unannounced "emergency."
      An additive sequence of cues indicated the probability of an emergency. Study I
      involved a three-group design with cue sequences that indicated the same risk at
      each decision point but whose final cue presented a high, medium, or low
      probability. Study 2 had a 2 x 2 design with high or low final cues and an easy
      or a challenging task. RESULTS: In Study I, participants stopped sooner when the
      most recent cue presented a high rather than low probability (p = .09), despite
      the same emergency risk. In Study 2, participants stopped sooner when the most
      recent cue presented a high rather than low probability for the challenging task
      but not for the easy task (p = .08). CONCLUSION: Stopping decisions appear
      sensitive to the most recent cue observed while experiencing task load.
      Participants responded to the same risks differently only on the basis of a
      change in presentation. APPLICATION: Findings may be relevant for research and
      training for hazardous jobs, such as subsurface coal mining, fishing, and
      trucking.

PMID- 23964415
TI  - Eyes-on training and radiological expertise: an examination of expertise
      development and its effects on visual working memory.
AB  - OBJECTIVE: Our aim was to examine the specificity of the effects of acquiring
      expertise on visual working memory (VWM) and the degree to which higher levels of
      experience within the domain of expertise are associated with more efficient use
      of VWM. BACKGROUND: Previous research is inconsistent on whether expertise
      effects are specific to the area of expertise or generalize to other tasks that
      also involve the same cognitive processes. It is also unclear whether more
      training and/or experience will lead to continued improvement on domain-relevant
      tasks or whether a plateau could be reached. METHOD: In Experiment I, veterinary
      medicine students completed a one-shot visual change detection task. In
      Experiment 2, veterinarians completed a flicker change detection task. Both
      experiments involved stimuli specific to the domain of radiology and general
      stimuli. RESULTS: In Experiment I, veterinary medicine students who had completed
      an "eyes-on" radiological training demonstrated a domain-specific effect in which
      performance was better on the domain-specific stimuli than on the domain-general
      stimuli. In Experiment 2, veterinarians again showed a domain-specific effect,
      but performance was unrelated to the amount of experience veterinarians had
      accumulated. CONCLUSION: The effect of experience is domain specific and occurs
      during the first few years of training, after which a plateau is reached.
      APPLICATION: VWM training in one domain may not lead to improved performance on
      other VWM tasks. In acquiring expertise, eyes-on training is important initially,
      but continued experience may not be associated with further improvements in the
      efficiency of VWM.

PMID- 23964416
TI  - Effects of anti-fatigue mats on perceived discomfort and weight-shifting during
      prolonged standing.
AB  - OBJECTIVE: The aim of this experiment was to investigate the effects of anti
      fatigue mats on perceived discomfort and behavioral responses (weight-shifting
      between the feet) during prolonged standing. BACKGROUND: Prolonged standing is a
      common requirement in the workplace and is a well-known cause of discomfort. Anti
      fatigue mats have been shown to reduce discomfort resulting from standing, but no
      study has identified a particular mat that performs better than others or
      examined the relationship between discomfort and weight-shifting. METHODS:
      Participants stood for 4 hours on four commercially available "anti-fatigue" mats
      and a hard surface (control condition). Subjective ratings of discomfort were
      measured, and in-shoe pressure was recorded and used to evaluate weight-shifting
      during standing. RESULTS: Compared to the control condition, after 4 hours of
      standing discomfort was reduced by three of the four mats, but discomfort ratings
      did not significantly differ among mats. However, significant differences among
      mats were found in the frequency of weight-shifting, and weight-shifting was
      positively correlated to discomfort. CONCLUSION: These results suggest that
      subjective reports of discomfort were not sufficiently sensitive to detect
      differences among mats for the experimental conditions tested. Behavioral
      responses, specifically weight-shifting between feet, may provide a more
      sensitive alternative to subjective reports.

PMID- 23964417
TI  - Individual differences in multitasking ability and adaptability.
AB  - OBJECTIVE: The aim of this study was to identify the cognitive factors that
      predictability and adaptability during multitasking with a flight simulator.
      BACKGROUND: Multitasking has become increasingly prevalent as most professions
      require individuals to perform multiple tasks simultaneously. Considerable
      research has been undertaken to identify the characteristics of people (i.e.,
      individual differences) that predict multitasking ability. Although working
      memory is a reliable predictor of general multitasking ability (i.e., performance
      in normal conditions), there is the question of whether different cognitive
      faculties are needed to rapidly respond to changing task demands (adaptability).
      METHOD: Participants first completed a battery of cognitive individual
      differences tests followed by multitasking sessions with a flight simulator.
      After a baseline condition, difficulty of the flight simulator was incrementally
      increased via four experimental manipulations, and performance metrics were
      collected to assess multitasking ability and adaptability. RESULTS: Scholastic
      aptitude and working memory predicted general multitasking ability (i.e.,
      performance at baseline difficulty), but spatial manipulation (in conjunction
      with working memory) was a major predictor of adaptability (performance in
      difficult conditions after accounting for baseline performance). CONCLUSION:
      Multitasking ability and adaptability may be overlapping but separate constructs
      that draw on overlapping (but not identical) sets of cognitive abilities.
      APPLICATION: The results of this study are applicable to practitioners and
      researchers in human factors to assess multitasking performance in real-world
      contexts and with realistic task constraints. We also present a framework for
      conceptualizing multitasking adaptability on the basis of five adaptability
      profiles derived from performance on tasks with consistent versus increased
      difficulty.

PMID- 23964418
TI  - Effect of sitting or standing on touch screen performance and touch
      characteristics.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of sitting and
      standing on performance and touch characteristics during a digit entry touch
      screen task in individuals with and without motor-control disabilities.
      BACKGROUND: Previously, researchers of touch screen design have not considered
      the effect of posture (sitting vs. standing) on touch screen performance
      (accuracy and timing) and touch characteristics (force and impulse). METHOD:
      Participants with motor-control disabilities (n = 15) and without (n = 15)
      completed a four-digit touch screen number entry task in both sitting and
      standing postures. Button sizes varied from 10 mm to 30 mm (5-mm increments), and
      button gap was 3 mm or 5 mm. RESULTS: Participants had more misses and took
      longer to complete the task during standing for smaller button sizes (< 20 mm).
      At larger button sizes, performance was similar for both sitting and standing. In
      general, misses, time to complete task, and touch characteristics were increased
      for standing. Although disability affected performance (misses and timing),
      similar trends were observed for both groups across posture and button size.
      CONCLUSION: Standing affects performance at smaller button sizes (< 20 mm). For
      participants with and without motor-control disabilities, standing led to greater
      exerted force and impulse. APPLICATION: Along with interface design
      considerations, environmental conditions should also be considered to improve
      touch screen accessibility and usability.

PMID- 23964419
TI  - Effects of knowledge and internal locus of control in groups of health care
      workers judging likelihood of pathogen transfer.
AB  - OBJECTIVE: A study was conducted to measure the effects of attitudes and beliefs
      on the risk judgments of health care workers. BACKGROUND: Lack of hand hygiene
      compliance is a worldwide issue in health care, contributing to infections,
      fatalities, and increased health care costs. Human factors methods are a
      promising solution to the problem of compliance, although thus far, the
      concentration has been on process and engineering methods, such as the design of
      no-touch sinks. Factors internal to the health care worker, such as their
      attitudes and beliefs about hand hygiene, have received less attention. METHOD:
      For this study, three groups of health care workers completed measures of
      attitudes, control beliefs, and hand hygiene knowledge. They then provided risk
      judgments of touching various surfaces via a factorial survey. RESULTS:
      Attitudes, knowledge, control beliefs, and surface type all predicted the risk
      judgments of the sample of health care workers, with differences between
      professional groups. CONCLUSION: Health care workers perceive less risk when
      touching surfaces,which may explain historically low rates of hand hygiene
      compliance after surface contact. APPLICATION: Although more research is needed
      to directly connect risk judgments to failures of hand hygiene, the current
      results can inform interventions targeting the internal attitudes and beliefs of
      health care workers.

PMID- 23964420
TI  - Are two hands (from different people) better than one? Mode effects and
      differential transfer between manual coordination modes.
AB  - OBJECTIVE: We report an experiment in which we investigated differential transfer
      between unimanual (one-handed), bimanual (two-handed), and intermanual (different
      peoples' hands) coordination modes. BACKGROUND: People perform some manual tasks
      faster than others ("mode effects"). However, little is known about transfer
      between coordination modes. To investigate differential transfer, we draw
      hypotheses from two perspectives--information based and constraint based--of
      bimanual and interpersonal coordination and skill acquisition. METHOD:
      Participants drove a teleoperated rover around a circular path in sets of two 2
      min trials using two of the different coordination modes. Speed and variability
      of the rover's path were measured. Order of coordination modes was manipulated to
      examine differential transfer and mode effects. RESULTS: Differential transfer
      analyses revealed patterns of positive transfer from simpler (localized
      spatiotemporal constraints) to more complex (distributed spatiotemporal
      constraints) coordination modes paired with negative transfer in the opposite
      direction. Mode effects indicated that intermanual performance was significantly
      faster than unimanual performance, and bimanual performance was intermediate.
      Importantly, all of these effects disappeared with practice. CONCLUSION: The
      observed patterns of differential transfer between coordination modes may be
      better accounted for by a constraint-based explanation of differential transfer
      than by an information-based one. Mode effects may be attributable to
      anticipatory movements based on dyads' access to mutual visual information.
      APPLICATION: Although people may be faster using more-complex coordination modes,
      when operators transition between modes, they may be more effective transitioning
      from simpler (e.g., bimanual) to more complex (e.g., intermanual) modes than vice
      versa. However, this difference may be critical only for novel or rarely
      practiced tasks.

PMID- 23964421
TI  - Training haptic stiffness discrimination: time course of learning with or without
      visual information and knowledge of results.
AB  - OBJECTIVE: In this study, we explored the time course of haptic stiffness
      discrimination learning and how it was affected by two experimental factors, the
      addition of visual information and/or knowledge of results (KR) during training.
      BACKGROUND: Stiffness perception may integrate both haptic and visual modalities.
      However, in many tasks, the visual field is typically occluded, forcing stiffness
      perception to be dependent exclusively on haptic information. No studies to date
      addressed the time course of haptic stiffness perceptual learning. METHOD: Using
      a virtual environment (VE) haptic interface and a two-alternative forced-choice
      discrimination task, the haptic stiffness discrimination ability of 48
      participants was tested across 2 days. Each day included two haptic test blocks
      separated by a training block Additional visual information and/or KR were
      manipulated between participants during training blocks. RESULTS: Practice
      repetitions alone induced significant improvement in haptic stiffness
      discrimination. Between days, accuracy was slightly improved, but decision time
      performance was deteriorated. The addition of visual information and/or KR had
      only temporary effects on decision time, without affecting the time course of
      haptic discrimination learning. CONCLUSION: Learning in haptic stiffness
      discrimination appears to evolve through at least two distinctive phases: A
      single training session resulted in both immediate and latent learning. This
      learning was not affected by the training manipulations inspected. APPLICATION:
      Training skills in VE in spaced sessions can be beneficial for tasks in which
      haptic perception is critical, such as surgery procedures, when the visual field
      is occluded. However, training protocols for such tasks should account for low
      impact of multisensory information and KR.

PMID- 23964423
TI  - The influence of cognitive load on transfer with error prevention training
      methods: a meta-analysis.
AB  - OBJECTIVE: The objective was to conduct research synthesis for the U.S.Army on
      the effectiveness of two error prevention training strategies (training wheels
      and scaffolding) on the transfer of training. BACKGROUND: Motivated as part of an
      ongoing program of research on training effectiveness, the current work presents
      some of the program's research into the effects on transfer of error prevention
      strategies during training from a cognitive load perspective. Based on cognitive
      load theory, two training strategies were hypothesized to reduce intrinsic load
      by supporting learners early in acquisition during schema development. METHOD: A
      transfer ratio and Hedges' g were used in the two meta-analyses conducted on
      transfer studies employing the two training strategies. Moderators relevant to
      cognitive load theory and specific to the implemented strategies were
      examined.The transfer ratio was the ratio of treatment transfer performance to
      control transfer. Hedges' g was used in comparing treatment and control group
      standardized mean differences. Both effect sizes were analyzed with versions of
      sample weighted fixed effect models. RESULTS: Analysis of the training wheels
      strategy suggests a transfer benefit. The observed benefit was strongest when the
      training wheels were a worked example coupled with a principle-based prompt.
      Analysis of the scaffolding data also suggests a transfer benefit for the
      strategy. CONCLUSION: Both training wheels and scaffolding demonstrated positive
      transfer as training strategies.As error prevention techniques, both support the
      intrinsic load--reducing implications of cognitive load theory. APPLICATION: The
      findings are applicable to the development of instructional design guidelines in
      professional skill-based organizations such as the military.

PMID- 23964424
TI  - NTP monograph on health effects of low-level lead.
AB  - Although reductions in lead (Pb) exposure for the U.S. population have resulted
      in lower blood Pb levels over time, epidemiological studies continue to provide
      evidence of health effects at lower and lower blood Pb levels. Low-level Pb was
      selected for evaluation by the National Toxicology Program (NTP) because of (1)
      the availability of a large number of epidemiological studies of Pb, (2) a
      nomination by the National Institute for Occupational Safety and Health for an
      assessment of Pb at lower levels of exposure, and (3) public concern for effects
      of Pb in children and adults. This evaluation summarizes the evidence in humans
      and presents conclusions on health effects in children and adults associated with
      low-level Pb exposure as indicated by less than 10 micrograms of Pb per deciliter
      of blood (< 10 microg/dL). The assessment focuses on epidemiological evidence at
      blood Pb levels < 10 microg/dL and < 5 microg/dL because health effects at higher
      blood Pb levels are well established. The NTP evaluation was conducted through
      the Office of Health Assessment and Translation (OHAT, formerly the Center for
      the Evaluation of Risks to Human Reproduction) and completed in April of 2012.
      The results of this evaluation are published in the NTP Monograph on Health
      Effects of Low-Level Lead. The document and appendices are available at
      http://ntp.niehs.nih.gov/go/evals. This document provides background on Pb
      exposure and includes a review of the primary epidemiological literature for
      evidence that low-level Pb is associated with neurological, immunological,
      cardiovascular, renal, and/or reproductive and developmental effects. The NTP
      Monograph presents specific conclusions for each health effect area. Overall, the
      NTP concludes that there is sufficient evidence that blood Pb levels < 10
      microg/dL and < 5 microg/dL are associated with adverse health effects in
      children and adults. This conclusion was based on a review of the primary
      epidemiological literature, scientific input from technical advisors that
      reviewed pre-public release drafts of each chapter summarizing the evidence for
      specific health effects associated with low-level Pb, public comments received
      during the course of the evaluation, and comments from an expert panel of ad hoc
      reviewers during a public meeting to review the Draft NTP Monograph on November
      17-18, 2011 (http://ntp.niehs.nih.gov/go/37090.

PMID- 23964422
TI  - Naturalistic distraction and driving safety in older drivers.
AB  - OBJECTIVE: In this study, we aimed to quantify and compare performance of middle
      aged and older drivers during a naturalistic distraction paradigm (visual search
      for roadside targets) and to predict older drivers performance given functioning
      in visual, motor, and cognitive domains. BACKGROUND: Distracted driving can
      imperil healthy adults and may disproportionally affect the safety of older
      drivers with visual, motor, and cognitive decline. METHOD: A total of 203
      drivers, 120 healthy older (61 men and 59 women, ages 65 years and older) and 83
      middle-aged drivers (38 men and 45 women, ages 40 to 64 years), participated in
      an on-road test in an instrumented vehicle. Outcome measures included performance
      in roadside target identification (traffic signs and restaurants) and concurrent
      driver safety. Differences in visual, motor, and cognitive functioning served as
      predictors. RESULTS: Older drivers identified fewer landmarks and drove slower
      but committed more safety errors than did middle-aged drivers. Greater
      familiarity with local roads benefited performance of middle-aged but not older
      drivers.Visual cognition predicted both traffic sign identification and safety
      errors, and executive function predicted traffic sign identification over and
      above vision. CONCLUSION: Older adults are susceptible to driving safety errors
      while distracted by common secondary visual search tasks that are inherent to
      driving. The findings underscore that age-related cognitive decline affects older
      drivers' management of driving tasks at multiple levels and can help inform the
      design of on-road tests and interventions for older drivers.

PMID- 23964436
TI  - Pandemic influenza (H1N1) 2009 of pediatric patients at Thammasat University
      Hospital.
AB  - BACKGROUND: An emerge of pandemic influenza H1N1 2009 has devastated the global
      community. Pediatric population is among the groups with high attack rate.
      OBJECTIVE: To study the clinical presentation of pediatric patients (0-15 years
      old) infected with influenza H1N1 2009 and to evaluate the sensitivity and
      specificity of the rapid influenza test. MATERIAL AND METHOD: Retrospective data
      was collected from the medical reports of patients presenting with influenza like
      illness (ILI) whose samples from nasal swab were tested for H1N1 using reverse
      transcription polymerase chain reaction (RT-PCR) during June-September 2009 at
      the Thammasat University Hospital. RESULTS: Of 68 patients, 26 were confirmed to
      have H1N1 2009 strain. Of these, 61.5% were older than 5 years old; 26.9% had
      underlying conditions and 38.4% had hospitalization. All 26 patients presented
      with fever and cough; 73% had coryza; 57.6% had sore throat; and 88.4% had
      injected throat. Six patients (23%) had pneumonia. Patients younger than 5 years
      old experienced dyspnea and had abnormal results of a chest radiograph
      significantly more often than patients older than 5. Patients with H1N1 2009
      strain were more likely to have sore throat, myalgia, and injected throat than
      non H1N1 2009 group. However chest wall retraction and abnormal chest radiograph
      were found significantly less often in the H1N1 group compared to the non-H1N1.
      No death case was reported. The rapid influenza test was found to have
      sensitivity of 80%, specificity of 64%, positive predictive value of 74.5%, and
      negative predictive value of 84.3% when compared to RT-PCR method. CONCLUSION:
      During pandemic period, older children with influenza like illness had novel H1N1
      2009 infection more than younger children. The majority of pediatric patients
      presented with mild symptoms. Patients aged below 5 years more frequently
      experienced pneumonia. The rapid influenza test showed a high sensitivity but low
      specificity.

PMID- 23964437
TI  - Health-related quality of life in children with chronic diseases at Thammasat
      University Hospital.
AB  - OBJECTIVE: The present study aimed to examine the level of health related quality
      of life in pediatric patients with common chronic diseases who sought care at
      Thammasat University Hospital. MATERIAL AND METHOD: Cross sectional study in 134
      patients aged 2-18, who visited department of pediatrics at Thammasat University
      Hospital were performed. Health related quality of life was evaluated using Thai
      version of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL
      4.0). For children aged 2-4 and 5-18, the questionnaire was answered by their
      guardians and by themselves and their guardians, respectively. The present study
      evaluated health related quality of life in four aspects: physical, emotional,
      social and school functioning. Points were then pooled and divided into three
      categories, namely total, physical health summary and psychosocial health summary
      scale scores. Each category could have a maximum score of 100. RESULTS: The mean
      total scale score from the questionnaire answering by guardians was highest in
      allergic rhinitis (77.6 +/- 12.1). Physical and psychosocial scale scores were
      81.7 +/- 16.8 and 75.4 +/- 12.5. Total scale scores in asthma, chronic renal
      diseases, leukemia and lymphoma, and congenital heart defects were 73.8 +/- 14.7,
      73.5 +/- 18.9, 64.5 +/- 14.0 and 76.2 +/- 19.6, respectively Cerebral palsy had
      the lowest total scale score of 27.1 +/- 16.7 with physical and psychosocial
      scale scores of 16.9 +/- 7.5 and 33.0 +/- 23.2, respectively. When patients
      answered the questionnaire by themselves, it was found that allergic rhinitis had
      the highest total scale score (79.5 +/- 13.2). Total scale scores in asthma,
      chronic renal diseases, leukemia and lymphoma, and heart diseases were 75.2 +/-
      16.4, 76.3 +/- 16.2, 70.5 +/- 9.4 and 72.4 +/- 22.7, respectively. Cerebral palsy
      had the lowest scale scores in all categories, with total scale score of 46.1 +/-
      14.6, physical scale score of 23.4 +/- 6.6 and psychosocial scale score of 58.3
      +/- 18.8. CONCLUSION: Among chronic diseases, cerebral palsy has the lowest
      health related quality of life scale scores in all categories, namely total,
      physical and psychosocial health summary.

PMID- 23964438
TI  - Association between UGT 1A1 Gly71Arg (G71R) polymorphism and neonatal
      hyperbilirubinemia.
AB  - BACKGROUND: Neonatal hyperbilirubinemia is a common problem in neonates and
      affects 60% of Asian newborn babies which is twice that found in Caucasians.
      These findings suggest that a genetic factor might be involved. Recently, a
      relationship between polymorphisms of the bilirubin uridine 5-diphosphate
      glucuronosyltransferase (UGTA1) gene and neonatal hyperbilirubinemia has been
      reported. It was demonstrated that the genetic variations cause a decrease in
      UGT1A1 activity in neonates, leading to an accumulation of unconjugated bilirubin
      in serum. However in Asians the G to A missense mutations in the UGTA1 at
      nucleotide 211 (known as G71R), were the predominant findings. Therefore, the
      impact of this polymorphism on serum bilirubin in healthy Thai neonates is of
      interest. OBJECTIVE: The aim of the present study was to investigate the
      frequency of UGT1A1 allele in healthy Thai neonates and to determine its role in
      neonatal hyperbilirubinemia. MATERIAL AND METHOD: A cross sectional study was
      conducted to investigate an association between the UGT1A1 G71R polymorphism and
      neonatal hyperbilirubinemia. Cord blood of 291 neonates was obtained to determine
      the gene frequency of UGT1A1 G71R by PCR-restriction fragment length polymorphism
      method. During the first 48 to 72 hours of the infants' life, the infants' blood
      was collected to measure their microbilirubin. RESULTS: PCR-RFLP analysis
      revealed the UGT1A1 G71R polymorphism in 42 infants (14.4%). In addition, six of
      this group (14.3%) had a microbilirubin level more than 95th percentile which was
      approximately 2.5 times more than those with the wild type allele (5.6%). The
      maximum microbilirubin level of infants in the R71 allele group was significantly
      higher than those in the G71 allele group, (11.79 +/- 3.34 mg/dL and 9.53 +/-
      2.34 mg/dL, respectively p < 0.01). CONCLUSION: In the present study, the UGT1A1
      G71R allele was found to be one of the risk factors for neonatal
      hyperbilirubinemia in Thai neonates.

PMID- 23964439
TI  - Effect of direct renin inhibitor monotherapy on proteinuria in overt diabetic
      nephropathy.
AB  - BACKGROUND: Diabetic nephropathy is one of the major causes of chronic kidney
      disease (CKD), consequently progression to end stage renal disease. The previous
      studies demonstrated that the inhibition on renin-angiotensin-aldosterone system
      (RAAS) such as by angiotensin converting enzyme inhibitor (ACEI) and angiotensin
      type I receptor blocker (ARB) reduced proteinuria and slow progression of CKD.
      Direct renin inhibitor (DRI) theoretical complete block RAAS by reducing plama
      renin activity angiotensin I and angiotensin II. The present study aimed to
      determine the efficacy of aliskiren (DRI) monotherapy on blood pressure control
      and proteinuria reduction. MATERIAL AND METHOD: Diabetic mellitus patients with
      estimated glomerular filtration rate (eGFR) > or = 30 ml/min who had proteinuria
      > 300 mg/day were enrolled to receive aliskiren 150 mg/day for 2 weeks then 300
      mg/day until 24 weeks. RESULTS: The SBP were significantly decreased form 137.8
      to 123.7 (p = 0.01) at 2 weeks, 137.8 to 126.26 (p = 0.04) at 4 weeks and 137.8
      to 121 mmHg (p = 0.002) at 24 weeks after treatment, respectively. Similar to
      SBP, the DBP was significantly decreased from 84.08 to 73.66 (p = 0.04) at 4
      weeks and 84.08 to 75.85 mmHg (p = 0.002) at the end of study. Reduction of UPCR
      showed significantly reduced for 32.65% (p = 0.007) and 45% (p = 0.004) from
      baseline at 2 weeks and 24 weeks after DRI treatment respectively. Serum
      creatinine, eGFR and serum potassium were no significant changed from the
      baseline. There were no harmful adverse reaction in patients who receiving
      aliskirin. CONCLUSION: Aliskiren monotherapy showed significantly reduced
      proteinuria, good blood pressure control without harmful side effect in overt
      diabetic nephropathy patients.

PMID- 23964440
TI  - Transthoracic echocardiography in Thai patients with acute ischemic stroke.
AB  - OBJECTIVE: Transthoracic echocardiography (TTE) is routinely performed to look
      for the cardiac sources of emboli in many Western stroke centers. Due to a
      limitation of resources in Thailand, echocardiography is done in only some
      patients with acute ischemic stroke. The purpose of this study is to evaluate the
      need for cardiac investigations, especially TTE, in Thai patients with acute
      ischemic stroke. MATERIAL AND METHOD: Two-hundred and seven patients with acute
      ischemic stroke or transient ischemic attack (TIA), who had TTE results during
      August 2006 to November 2008, were studied. Patients were divided into 2 groups
      by the risk of cardioembolism: low- versus high-risk groups. All echocardiography
      results were reviewed and classified by the need for management change following
      the echocardiography. RESULTS: Abnormal TTE results indicating a need for change
      in management were found in 4% (4/102) and 18% (18/105) in low- and high- risk
      patients, respectively The results of ECG alone led to change in management in
      17% (36 patients). Atrial fibrillation was the most common cause of
      cardioembolism, which was found in 35 patients (17%). CONCLUSION: Because of
      limited resources in Thailand, ECG should be routinely performed on all ischemic
      stroke patients and TTE in patients with high risk for cardioembolism. However
      larger studies are still needed to clarify the benefits of echocardiography in
      low-risk patients.

PMID- 23964441
TI  - Efficacy of video-assisted thoracoscopic surgery (VATS) for management of empyema
      thoracis.
AB  - OBJECTIVE: Empyema thoracis is a frequent clinical problem and share in common a
      considerable potential for death and morbidity. Video-assisted thoracoscopic
      surgery [VATS] debridement or decortication become popular and increase the
      available treatment options. The authors aim is to determine the efficacy and
      outcome of VATS for management of empyema thoracis in adult patients. MATERIAL
      AND METHOD: A retrospective study of all adult patient treated for empyema
      between June 2009 to Feb 2011 at Thammasat Hospital was conducted. Recorded data
      included demographic information, clinical presentation, laboratory data,
      microbiological data, operative details, postoperative course, follow-up data and
      complications. RESULTS: A total of 23 patients [5 women, 18 men] underwent VATS
      debridement and decorication for treatment of empyema thoracis. Their mean age
      was 57 [35-90] years. 17 [74%] patients received preoperative drainage
      [percutaneous catheter drainage or tube thoracostomy] and mean duration of
      preoperative drainage was 7.6 [3-26] days. 8 [35%] patients had stage II empyema
      and underwent VATS debridement while 15 [74%] patients had stage III empyema
      underwent VATS decortication. Median postoperative hospital stay was 12.6 [7-48]
      days. Median time for postoperative intercostals drainage was 5 [3-30] days.
      Median follow-up time was 5 [1-20] months. Conversion rate to open thoracotomy
      for stage II empyema was only 13%. There were 3 postoperative complications
      [13%]: wound infection [n = 1], persistent space [n = 1] and recurrent infection
      [n = 1]. There was no intraoperative death and 2 [8%] perioperative death [< 30
      days] which were mostly unrelated to surgery. Of the 23 patients, 20 patients
      [87%] achieved satisfactory results with treatment. CONCLUSION: VATS debridement
      and decortication is safe and effective treatment in the management of stage II
      and stage III empyema thoracis.

PMID- 23964442
TI  - Maternal acceptance, attitude and knowledge on human papilloma virus vaccination
      for their daughters.
AB  - OBJECTIVE: To compare the basic knowledge scores, attitudes and acceptability to
      HPV immunization before and after acknowledge about HPV, cervical cancer and
      vaccine to study group. MATERIAL AND METHOD: An anonymous survey was applied to
      women attending the outpatient clinic, Thammasat University Hospital from April
      2010 to October 2010. Basic knowledge about cervical cancer, HPV, HPV vaccine,
      attitudes and acceptability to HPV immunization were collected via a self
      administered questionnaire. RESULTS: A total of 173 mothers completed the survey
      responses rate of 86.5% (173/200). There is no difference in characteristic and
      lifestyles of the responders. The basic knowledge scores was higher in the
      subjects who had higher education level and regular cervical screening history.
      Most of subjects (> 85%) recognized that HPV is associated with cervical cancer
      but more than half of them confused about route of transmission. Basic knowledge
      scores is increased in all acceptability group (strongly agree to strongly
      disagree) after be informed about HPV and vaccine was observed. Most subjects
      (78.6%) agree to their daughters' vaccination indicating the high vaccine
      acceptances. The leading factors to maternal acceptances were free vaccination,
      negative attitudes such as sexual behavior of daughters and positive attitudes
      such as vaccine efficacy. DISCUSSION: HPV vaccine acceptance seems to be depended
      on cost and efficacy than maternal knowledge. The vaccine is not widely used. The
      cost-effectiveness analysis should be provided by government. Education and
      communication in public media are aimed for increasing coverage of vaccination in
      the future. CONCLUSION: Maternal acceptances of vaccine depend on high efficacy
      and low cost.

PMID- 23964443
TI  - Disaster medicine in Thailand: a current update. Are we prepared?
AB  - OBJECTIVE: To investigate the level of major incident/disasters preparedness in
      Thailand by evaluating to-date data with main focus on past events and their
      outcomes to alert national medical societies for their roles in upcoming
      disasters/major incidents. MATERIAL AND METHOD: Besides data from past
      disasters/major incidents (Jan 2006-Dec 2010), including injury details in each
      event; all information about current disasters/major incidents preparedness
      systems, triage and pre-hospital management, standard of personnel, co-ordination
      and command centers, were reviewed by using data from Bangkok Emergency Medical
      Service, Narenthorn EMS of Rajavithi Hospital, Emergency Medical Institute of
      Thailand, Royal Thai Police, Department of Disaster prevention and mitigation
      (Ministry of Interior). RESULTS: There was neither a national registry, nor an
      authentic centralization of the preparedness system. The current organization was
      found to be functional, but incomplete. The main dispatch center responsible for
      medical service in Bangkok metropolitan during the present study period was
      Bangkok EMS ("Erawan center"). In provincial areas, emergency medical services
      (Ministry of Public Health) in each province act as dispatcher in their
      corresponding regions in cooperation with the emergency operation divisions in
      their related area. Several private organizations also volunteered to assist.
      There was an increase in the number of disasters/major incidents in Thailand
      between 2006 and 2010; with a total number of 60,999 deaths, 346,763 wounded
      patients and 73 missing and total costs of 47,453.69 million Baht (1,581.79
      million US Dollar). DISCUSSION AND CONCLUSION: There is an established and
      functional disaster management organization in Thailand with some overlapping
      difficulties and a need for improvement. Understanding the national need for
      registry, public information, preparedness, cooperation and coordination inside
      and outside hospitals, will not only save lives, but also would be beneficial for
      the country in terms of major economical measures.

PMID- 23964444
TI  - The efficacy of Curcuma Longa L. extract as an adjuvant therapy in primary knee
      osteoarthritis: a randomized control trial.
AB  - Nonsteroidal anti-inflammatory Drugs (NSAIDs) is one of the most commonly use
      medication for treatment of knee osteoarthritis which has the analgesic and anti
      inflammation by inhibition of prostaglandin synthesis via COX-1 and COX-2
      isoenzyme. The problem of prolong using NSAIDs has side effect on kidney, liver
      and GI system. Curcumin longa extract Curcumin) is the Asian herbal medicine that
      has the anti-inflammatory effect by down regulate activation of NF-kappaB and
      proinflammatory cytokines such as Tumor Necrotic Factor-alpha, Interleukin-1,
      Interleukin-8, and Nitric Oxide Syntase. Many research data had advocate for the
      combination therapy which can increase safety and efficacy with less side effect
      compare with monotherapy regimen especially when the medicine has the different
      mechanism of action. The present study is the double blind prospective randomized
      control trial to evaluate the efficacy of curcumin as an adjuvant therapy of
      diclofenac in primary knee osteoarthritis. 44 patients were randomized to take
      NSAIDs (diclofenac) 75 mg/d with placebo and the other 44 took NSAIDs
      (diclofenac) 75 mg/d with curcumin 1,000 mg/d for 3 months. The authors evaluated
      the Visual Analog Scale (VAS) for pain and Knee Injury and Osteoarthritis Outcome
      Score (KOOS) every month for 3 months. At the end of study 36 patients were
      completed for the first group and 37 for the study group. There was no difference
      in VAS [p-value = 0.923 (F = 0.009)]. The KOOS was analyzed in 5 categories
      symptom, pain, function in daily living, function in sport and recreation and
      knee related quality of life. The curcumin with diclofenac group had tendency to
      be better in Pain and Function in daily living, but there were no statistic
      different in all group [p-value = 0.412 (F = 0.683), p-value = 0.814 (F = 0.056),
      p-value = 0.446 (F = 0.589), p-value = 0.224 (F = 1.511) and p-value = 0.938 (F =
      0.006)]. In conclusion, the adjuvant therapy ofcurcumin with diclofenac has the
      potential beneficial effect in comparison with diclofenac alone, but no
      statistical significance.

PMID- 23964445
TI  - The efficacy of powdered ginger in osteoarthritis of the knee.
AB  - Ginger is an effective treatment against nausea and vomiting but there are only a
      few clinical studies of the effect as an anti-inflammatory or analgesic agent. A
      double-blind randomized controlled trial of one gram of powdered ginger per day
      in a capsule compared with a placebo in patients with osteoarthritic knees was
      carried out. The number of participants in each group was thirty. The length of
      treatment was eight weeks. The efficacy of the drug was monitored by using the
      Knee Injury and Osteoarthritis Outcome Score (KOOS). The authors used repeated
      ANOVA to compare scores between each group. One gram ofpowdered ginger per day
      did not improve kneejoint pain, symptoms, daily activities, sports activities and
      quality of life compared with a placebo. Prominent side effects did not occur The
      systolic and diastolic blood pressure, body mass index and blood chemistry were
      not changed after receiving treatment. The present study showed that one gram per
      day of powdered ginger could not relieve joint pain and improve symptoms and the
      quality of life during eight weeks of-treatment of osteoarthritis of the knee
      compared with the placebo.

PMID- 23964446
TI  - Do NSAIDs inhibit growth of precancerous cervical cells in vitro?
AB  - BACKGROUND: Cervical cancer is one of the most common cancers worldwide. A
      promising, novel strategy for cancer treatment is chemoprevention. Non-steroidal
      anti-inflammatory drugs (NSAIDs) have chemopreventive effects on several cancers
      including those of cervix. There are few clinical trials of the effects of NSAIDs
      on precancerous cervical lesions but data from in vitro studies are lacking.
      OBJECTIVE: To study growth inhibitory effects of nonselective and selective
      NSAIDs on immortalized cervical cells in vitro. MATERIAL AND METHOD: Cytotoxicity
      of ibuprofen and celecoxib on immortalized cervical cells was analyzed by Cell
      Proliferation (MTT) Assay. Propidium Iodide (PI) Assay was used to analyze
      apoptotic cell death. RESULTS: Ibuprofen and celecoxib had significant growth
      inhibitory effects with IC50 of 3.00 +/- 0.44 mM and 30. 00 +/- 11.00 uM,
      respectively. Both drugs significantly induced apoptosis. CONCLUSION: Ibuprofen
      and celecoxib can inhibit growth and induce apoptotic cell death in immortalized
      cervical cells. results from the present study highlight the need for further in
      vivo researches and clinical trials in search of novel strategies for cervical
      cancer prevention.

PMID- 23964447
TI  - Fine needle aspiration of thyroid: a cyto-histopathological correlation in
      Ramathibodi Hospital.
AB  - OBJECTIVE: To evaluate the accuracy of fine needle aspiration cytology (FNAC) of
      thyroid lesions in Ramathibodi patients. MATERIAL AND METHOD: A retrospective
      review is performed on 469 cases of thyroid surgical pathology specimens with
      previous FNAC reports; during January 2005 to January 2008. All histopathology
      reports are compared to the latest previous cytopathology results which are
      categorized as unsatisfactory, benign, inconclusive, borderline and malignancy
      RESULTS: The cytopathology results showed 74 cases (15.7%) of unsatisfactory
      specimens, 243 cases (51.8%) of benign lesions, 33 cases (7%) of inconclusive
      lesions, 15 cases (3.2%) of borderline lesions and 104 cases (22%) of malignant
      lesions. The histopathology results for benign lesions reveal multinodular and
      nodular goiter of 236 cases and other diagnosis of 54 cases. The histopathology
      results for malignant lesions were papillary carcinoma of 147 cases, follicular
      carcinoma of 24 cases and other malignancy of 8 cases. Among 243 cases of benign
      from FNAC; 23 cases turn out to be malignancy while 104 cases of malignancy from
      FNAC show no false positive. The sensitivity, specificity, positive predictive
      value, negative predictive value and accuracy of FNAC are 81.9%, 100%, 100%,
      90.4% and 93.4% respectively. CONCLUSION: FNAC is a minimally invasive, highly
      accurate and cost-effective procedure. In our setting the FNAC enable the
      clinician to "rule-in" malignant lesions with confidence.

PMID- 23964448
TI  - Accuracy of abnormal pap smear at Thammasat University Hospital.
AB  - The aim of the present study was to assess the sensitivity, specificity and
      accuracy of the Pap smear in the diagnosis of squamous intraepithelial lesion
      (SIL) and squamous cell carcinoma (SCC). Pap smear of 15,345 women in 2 years
      were screened for early detection of abnormal cervix. In 299 cases (1.9%) were
      diagnosed as low-grade SIL (LSIL), high-grade SIL (HSIL) and SCC by the Bethesda
      system (TBS) 2001. Only 195 cases (1.3%) had definitive histologic diagnosis as
      negative, human papilloma virus (HPV) infection, cervical intraepithelial
      neoplasia (CIN) 1, CIN 2, CIN 3 and SCC. The sensitivity, specificity and
      accuracy in LSIL was 86.5%, 70% and 71.3%, respectively. For HSIL it was 80.8%,
      89.7% and 86.2%, respectively. For SCC it was 100%, 96.9% and 96.9%,
      respectively. Our data had high diagnostic performance for HSIL and SCC group and
      moderate diagnostic performance for LSIL group.

PMID- 23964449
TI  - Workload and attitude toward profession among young Thai psychiatrists: a
      national survey.
AB  - OBJECTIVE: To survey workload and attitude toward profession of young Thai
      psychiatrists. MATERIAL AND METHOD: The present study was a cross sectional
      descriptive survey The researcher team invented the questionnaire and posted it
      to 142 young Thai psychiatrists (age < or = 40 years old). RESULTS: There were 82
      participants. Response rate was 57.7%. The respondents were 30 males (36.6%), 52
      females (63.4%), 66 general psychiatrists (80.5%), 16 child and adolescent
      psychiatrists (19.5%). Their mean of age was 31.4 years old. Those worked at
      hospitals under the Department of Mental Health (36.6%), the Office of Permanent
      Secretary (29.7%), universities (13.4%) and other institutions (12.2%). In office
      hours, the respondents had an average working hour 39.5 hours/week, while an
      average outpatient service working hour 15.6 hours/week. An average amount of
      outpatients was 89.9 patients/week. Each institution was significantly different
      in consultation liaison, teaching, administration, community psychiatry, and
      research. The percentages of young psychiatrists who agreed with the opinions
      "proud to be a psychiatrist", "working effectively as a psychiatrist" and
      "satisfied with psychiatric working system" were 98.9, 95.1 and 65.9
      respectively. The average amount of outpatients (patients/week) affected job
      satisfaction. CONCLUSION: The full-time working hour of young Thai psychiatrists
      was not different from other studies. However they had more psychiatric patients
      and spent more time doing outpatient service because of scarcity of psychiatrists
      in Thailand. Even though the number of psychiatric outpatients affected job
      satisfaction, most of them had positive professional attitude.

PMID- 23964450
TI  - Mental health status, including depression and quality of life among members of
      an elderly club in suburban Bangkok.
AB  - BACKGROUND: Evolution of medical technologies extent human life expectancy. The
      United Nations found Thai elderly population were increased rapidly compared with
      other developing countries. Global estimations of the burden of disease show that
      mental illness plays a prominent role. Elderly club is one of the several ways to
      promote social interaction, gain self esteem, slow progression of physical and
      mental disabilities in old age people. However, the activities which certainly
      proper for each elderly group remains unclear because various demographic data
      background of elderly in each area. OBJECTIVE: To determine the mental health
      status, including depression and quality of life among members of the Thammasat
      hospital elderly club which covers elderly members in northen Bangkok,
      Pathumthani and Ayutthaya province. MATERIAL AND METHOD: A cross-sectional
      descriptive study was conducted. Seventy members were sampled for interview from
      207 members. The assessment tools were Thai Mental Health Indicator (TMHI-54),
      Thai Geriatric Depression Scale (TGDS), Stress self assessment questionnaire, and
      World Health Organization Quality of Life-Brief-Thai Version (WHOQOL-BREF-THAI).
      RESULTS: The majority of the sample was females (78.6%). The age ranged from 60
      to 84 years old (mean 70.24). The prevalences of psychological problems were;
      poor mental health (12.90%), depression (5.7%) and stress (15.2%). The sample
      reported poorer quality of life on 3 sub-domains of WHOQOL; physical (2.9%),
      psychological (1.4%) and social relationship (4.30%) domains. The level of
      depression, reported by those who had not enough income, was significantly higher
      than those who had enough income (p = 0.022). Quality of life (physical and
      social relationship domain) among those aged younger than 70 years, was better
      than that among those aged 70 or older (p = 0.024 and p = 0.023 respectively).
      Quality of life (psychological domain) among those who had not enough income, was
      significantly poorer than those with enough income (p = 0.020). Quality of life
      in term of social relationship was better among those living in urban areas (p =
      0.037) or having better education (p = 0.014). Regular or irregular club's
      activity attending was not related with mental status and quality of life.
      CONCLUSION: The majority of the sample had equal or better mental health status
      and quality of life compared with the general population. The prevalence of
      depression was slightly lower than other Thai studies.

PMID- 23964451
TI  - Kinetic inhibition of human salivary alpha-amylase by a novel cellobiose
      containing tetrasaccharide.
AB  - OBJECTIVE: The aim of the study was to evaluate the inhibitory kinetics of a
      novel cellobiose-containing tetrasaccharide on human salivary alpha-amylase
      (HSA). MATERIAL AND METHOD: Synthesis of cellobiose-containing tetrasaccharide
      was catalyzed by Paenibacillus sp. All CGTase using beta-CD as a donor and
      cellobiose as an acceptor under the optimal conditions. The reaction mixture was
      analyzed by HPLC and a cellobiose-containing tetrasaccharide obtained was studied
      for its inhibitory kinetics. RESULTS: In vitro activity of human salivary alpha
      amylase showed the optimum pH and temperature at 7.0 and 37 degrees C,
      respectively. The effects of metal ions, protective chemicals and saccharides on
      alpha-amylase activity, they were found that 10 mM concentration of CaCl2 and
      NaCl enhanced the enzyme activity. In contrast, the enzyme activity was
      significantly inhibited by 10 mM of HgCI2, alpha-cyclodextrin (alpha-CD) and
      synthetic cellobiose-containing tetrasaccharide. Chemicals often used as
      protective substance for enzyme such as beta-mercaptoethanol, EDTA or used as
      fungicide during enzyme purification (NaN3) had no effect on the activity of this
      enzyme. As a cellobiose-containing tetrasaccharide was shown to have a pronounce
      inhibition on alpha-amylase activity. Its inhibition kinetic was performed and
      found that cellobiose-containing tetrasaccharide was a competitive inhibitor with
      a Ki value of 7.89 microM. CONCLUSION: Inhibition kinetic of a cellobiose
      containing tetrasaccharide on alpha-amylase activity was competitive type with Ki
      value of 7.89 microM. In addition, these results will be a basic knowledge in
      controlling alpha-amylase actions that have influence on blood glucose level of
      trial animal and human further

PMID- 23964452
TI  - Antigenotoxic activity of Thai Sangyod red rice extracts against a
      chemotherapeutic agent, doxorubicin, in human lymphocytes by sister chromatid
      exchange (SCE) assay in vitro.
AB  - BACKGROUND: Nowadays, anticarcinogenic potential of pigmented brown rice and rice
      bran varieties have been increasingly stated. However, their mechanisms of action
      are still inconclusive. One of which might be their antigenotoxic activity that
      no study in human cells was reported before. OBJECTIVE: To evaluate the
      antigenotoxic activities of Thai Sangyod red rice extracts against a
      chemotherapeutic agent, doxorubicin, by sister chromatid exchange (SCE) assay in
      human lymphocytes in vitro. MATERIAL AND METHOD: Two fractions of water-soluble
      of Sangyod rice extracts were used: (i) the washed water extract of brown rice
      (WWBR) and (ii) the water extract of rice bran (WERB). Human lymphocytes were
      pretreated with each extracts at concentrations of 6.2, 12.5, 25, 50 and 100
      microg/ml for 2 h followed by a genotoxic agent, doxorubicin (DXR) (0.1
      microg/ml) for 2 h. SCE level, mitotic index (MI) and proliferation index (PI)
      were evaluated. Statistical analysis by Dunnett's t-test was performed. RESULTS:
      The results indicated that the pretreatment of WERB fraction only at
      concentration of 6.2 microg/ml could significantly decrease SCE level as compared
      to that of the DXR treated alone (p < 0.05). On the other hand, WERB fraction at
      other concentrations and all WWBR pretreatments could not. In addition, there was
      no significant difference in MI and PI levels between all pretreated extracts as
      compared to the DXR treated alone. CONCLUSION: Our data revealed that WERB
      pretreatment only at specific low concentration of 6.2 microg/ml possessed the
      antigenotoxic potential against genotoxic damage but not anticytotoxic induced by
      DXR. Further work is still needed to clarify more the antigenotoxic and
      anticytotoxic potentials from other fractions of Sangyod rice extracts.

PMID- 23964453
TI  - Fracture resistance of endodontically treated teeth restored with fiber
      reinforced composite posts and composite core with varying remaining coronal
      tooth structure.
AB  - BACKGROUND: Endodontically treated teeth often have a varying remaining coronal
      tooth structure, is an important factor in the successful of post-core with crown
      restoration. OBJECTIVE: This study compared the fracture resistance of pulpless
      teeth with variable amounts of remaining coronal tooth structure restored with
      fiber-reinforced composite posts and composite core. MATERIAL AND METHOD: Fifty
      extracted human premolars were endodontically treated and divided into 5 groups
      of 10 teeth each. Four groups were prepared having axial wall heights of 4 mm
      around the preparation circumferences. In 3 of the groups with axial tooth
      structure, mesial axial tooth structure was removed, mesial and lingual axial
      tooth structure were removed, mesial-lingual and distal axial tooth structure
      were removed. For the fifth group, all axial tooth structure was removed to the
      level of the prepared finish line. All 50 prepared teeth were restored with fiber
      reinforced composite posts (FRC Postec Plus) and composite resin cores (Multicore
      Flow). Testing was conducted with a universal testing machine with the
      application of a static load to the lingual incline plane of buccal cusp at a
      crosshead speed of 5 mm/min at 45 degrees to the long axis of the tooth. The load
      at failure was recorded. The data were subjected to 1-way analysis of variance.
      RESULTS: The mean value + standard deviation for the failure load of group 1 to 5
      were 237.48 +/- 81.87, 242.97 +/- 66.80, 257.67 +/- 70.42, 239.56 +/- 70.42 and
      297.70 +/- 99.42 (N), respectively There were no significant differences in the
      fracture resistance (p < 0.01). No root fractures occurred in any of the groups.
      CONCLUSION: The varying remaining coronal tooth structure of endodontically
      treated tooth had no influenced on the fracture resistance when restored with
      fiber-reinforced composite posts and composite core.

PMID- 23964454
TI  - Antioxidant and anti-inflammatory activities of Thai medicinal plants in
      Sahasthara remedy for muscle pain treatment.
AB  - OBJECTIVE: Twenty one plants as ingredients of Thai traditional preparation
      called Sahasthara for relieve muscles pain and distal numbness were studied for
      their antioxidant and anti-inflammatory activities. MATERIAL AND METHOD: The
      extracts were obtained by maceration with 95% ethanol. They were tested for their
      antioxidant activity by DPPH scavenging assay and anti-inflammatory activity by
      determination of inhibitory activity on lipopolysaccharide (LPS) induced nitric
      oxide (NO) production in RAW 264.7 cell lines using Griess reagent. RESULTS: The
      ethanolic extract of Terminalia chebula Retz. (Gall) showed the highest
      antioxidant activity (EC50 = 3.34 microg/ml). Its fruit extract also exhibited
      the most potent inhibitory activity on lipopolysaccharide (LPS) induced nitric
      oxide (NO) production in RAW 264.7 cells, followed by Atractylodes lancea and
      Baliospermum montanum (IC50 = 3.3, 9.7 and 12.6 microg/ ml, respectively).
      CONCLUSION: The results obtained for anti-inflammatory and antioxidant activities
      of these plants correspond with their traditional use for muscle pain and
      inflammatory-related diseases.

PMID- 23964455
TI  - In vitro cytotoxic activity of Benjakul herbal preparation and its active
      compounds against human lung, cervical and liver cancer cells.
AB  - BACKGROUND: Benjakul [BEN], a Thai Traditional medicine preparation, is composed
      of five plants: Piper chaba fruit [PC], Piper sarmentosum root [PS], Piper
      interruptum stem [PI], Plumbago indica root [PL] and Zingiber officinale rhizome
      [ZO]. From selective interviews of folk doctors in Southern Thailand, it was
      found that Benjakul has been used for cancer patients. OBJECTIVE: To investigate
      cytotoxicity activity of Benjakul preparation [BEN] and its ingredients against
      three human cancer cell lines, large lung carcinoma cell line (COR-L23), cervical
      cancer cell line (Hela) liver cancer cell line (HepG2) as compared with normal
      lungfibroblast cell (MRC-5) by using SRB assay. MATERIAL AND METHOD: The
      extraction as imitated the method used by folk doctors was done by maceration in
      ethanol and boiling in water Bioassay guided isolation was used isolated
      cytotoxic compound. RESULTS: The ethanolic extracts of PL, ZO, PC, PS, BEN and PS
      showed specific activity against lung cancer cell (IC50 = 3.4, 7.9, 15.8, 18.4,
      19.8 and 32.91 microg/ml) but all the water extracts had no cytotoxic activity.
      Three active ingredients [6-gingerol, plumbagin and piperine as 0.54, 4.18 and
      7.48% w/w yield of crude extract respectively] were isolated from the ethanolic
      extract of BEN and they also showed cytotoxic activity with plumbagin showing the
      highest cytotoxic activity against COR-L23, HepG2, Hela and MRC-5 (IC50 = 2.55,
      2.61, 4.16 and 11.54 microM respectively). CONCLUSION: These data results may
      support the Thai traditional doctors who are using Benjakul to treat cancer
      patients and three of its constituents (6-gingerol, plumbagin and piperine) are
      suggested to be used as biomarkers for standardization of this preparation.

PMID- 23964456
TI  - Using 6-gingerol content and gene mapping for identification of two types of
      ginger used in Thai traditional medicine.
AB  - BACKGROUND: Two species of ginger were used in Thai traditional medicine as
      Zingiber officinale Roscoe and Zingiber ligulatum Roxb. OBJECTIVE: To investigate
      for identification two types of ginger by morphological and microscopic
      characters, DNA profiles, and determination of 6-gingerol content by HPLC.
      MATERIAL AND METHOD: Fresh rhizomes of two gingers, their ages more than one year
      were collected from 12 sources in 4 parts of Thailand. The fresh leaves were also
      collected for studying DNA profile by amplified fragment length polymorphism
      (AFLP) method. RESULTS: The morphological characters of two types of gingers were
      almost corresponded to AFLP patterns and they were identified as Z officinale
      Rocs. and Z. ligulatum Roxb. Microscopic examinations of dried rhizomes from the
      both species showed the same pattern. By means of HPLC and TLC methods, 6
      gingerol content was found only in Z. officanale in range of 2.58-17.04% but
      disappeared in Z. ligulatum. CONCLUSION: Determination of 6-gingerol content by
      HPLC or TLC pattern can be used to identified two types of ginger used in Thai
      Traditional Medicine.

PMID- 23964457
TI  - Anti-inflammatory and antioxidant activities of extracts from Musa sapientum
      peel.
AB  - BACKGROUND: Many parts of Musa sapientum Linn. (Musaceae) are used in Thai
      traditional medicine as drugs, food supplements and cosmetics. The banana peel is
      used as an astringent in foot care, the unripe fruit is used to treat diarrhea
      and, the ripe fruit is used as tonic. OBJECTIVE: To evaluate anti-inflammatory
      and antioxidant activities of banana peel extracts obtained from different
      extraction methods and to determine their total phenolic content. MATERIAL AND
      METHOD: Four extraction methods were used to extract unripe and ripe peels.
      Nitric oxide inhibitory and DPPH scavenging assays were used to evaluate anti
      inflammatory and antioxidant activities, respectively. Folin-Ciocalteu's reagent
      was used to determine total phenolic content. RESULTS: The water extract of fresh
      ripe peel exhibited the most potent NO inhibitory activity (IC50 = 6.68 +/- 0.34
      microg/ml), but apparently exhibited no antioxidant activity. The decoction
      extract of fresh unripe peel exhibited strong antioxidant activity as well as had
      the highest total phenolic compound. The antioxidant activity exhibited a
      correlation with the total phenolic content. CONCLUSION: This study supports the
      use of Musa sapientum peel in Thai Traditional Medicine for treatment of
      inflammatory-related diseases.

PMID- 23964458
TI  - Comparison of antimicrobial, antioxidant activities and total phenolic content of
      Antidesma thwaitesianum fruit extracts by different methods.
AB  - BACKGROUND: Antidesma thwaitesianum Mull. Arg. is a tropical fruit in Northeast
      Thailand and its fruits are used for soft drink and healthy food. The biological
      activities of extracts from Antidesma thwaitesianum using different extraction
      methods have not been reported. OBJECTIVE: Extracts from Antidesma thwaitesianum
      using different extraction methods were tested for antibacterial and antioxidant
      activities as well as were determined for total phenolic content. Ten extracts
      were tested for antimicrobial activity by disc diffusion, MIC, and MBC methods.
      DPPH assay was used to test antioxidant activity and Folin-Ciocalteu 's reagent
      was used to determine total phenolic content. RESULTS: The extract obtained by
      decocting residue after maceration process of dried marc (MRW) exhibited stronger
      antioxidative power (EC50 = 11.73 microg/ml) than BHT (EC50 = 13.36 microg/ml).
      This antioxidant activity was related to total phenolic content of 85.77 +/- 0.34
      mg GAE/g. This extract also exhibited antimicrobial activity against
      Staphylococcus aureus (inhibition zone = 8 mm, MIC = 2.5 mg/ml). Moreover the
      extract obtained by macerating dried marc (MME) exhibited antimicrobial activity
      against Bacillus subtilis with the same MIC value of 10 mg/ml. CONCLUSION: All of
      the extracts of Antidesma thwaitesianum had less potential for antimicrobial
      activity than Gentamicin and Amphotericin B. On the other hand, the water extract
      especially obtained by decocting residue after maceration of dry marc had good
      antioxidant power and the highest total phenolic content. Thus, such water
      extract should be recommended for a good source of natural antioxidants for
      commercial uses.

PMID- 23964459
TI  - Antimicrobial, antioxidant activities and total phenolic content of Thai
      medicinal plants used to treat HIV patients.
AB  - BACKGROUND: Opportunistic infections in AIDs patients is the leading cause of
      death in among them. HIV infection was reported as causes of increasing oxidative
      stress which may lead to progress of many syndrome. Thus medicinal plants as
      demonstrated antimicrobial and antioxidant activities would be therapeutic values
      to treat opportunistic infections of AIDs patients. OBJECTIVE: To investigate
      antibacterial, antioxidant activities and total phenolic contents of five Thai
      medicinal plants using by Thai traditional doctors to treat opportunistic
      infections of AIDs patients such as Dioscorea bulbifera L. (DB), Momordica
      charantia L. (MC), Caricapapaya L. (female and male trees, CPF and CPM) and
      Phyllanthus amarus Schum & Thonn. (PA). MATERIAL AND METHOD: The ethanolic and
      water extracts of those herbs were tested. For antioxidant method was measured
      using DPPH radical scavenging assay, anti-microbial activity using disc diffusion
      assay and minimal inhibitory concentration (MIC) was determined by using the
      modified resazurin assay against four species of micro-organisms: Bacillus
      subtilis, Escherichia coli, Staphylococcus aureus and Candida albicans. Total
      phenolic content was determined by Folin-Ciocalteau colorimetric method. RESULTS:
      For water extract of PA showed the highest antibacterial activity against S.
      aureus (MIC value = 0.625 mg/ml). The ethanolic extract of MC showed the highest
      activity against B. subtilis (MIC = 0.625 mg/ml). Only ethanolic extract of DB
      inhibited growth of E. coli (MIC = 5 mg/ml) it also inhibited growth of gram
      positive bacteria such as S. aureus and B. subtilis with the same MIC values (2.5
      mg/ml). No plant extracts showed activity against C. albicans. The ethanolic
      extract of CPM, PA and DB and the water extract of PA showed high antioxidant
      activity (EC50 of 8.48, 9.54, 11.07 and 11.37 microg/ml, respectively). The water
      extract of PA and the ethanolic extract of DB, CPM showed high total phenolic
      content of 262.54, 106.26 and 83.78 mg/g, respectively. The total phenolic
      content of these extracts correlated with DPPH radical scavenging activity, while
      only ethanolic extract of PA showed high antioxidant activity (9.54 microg/ml)
      but it contain low phenolic content (45.50 mg/g). CONCLUSION: Our findings
      support the usage of the these plants to treat opportunistic infection of Thai
      traditional doctors in AIDs patients. Thus, it is recommended that the isolation
      of pure active antibacterial and antioxidant from these plant extracts should be
      carried on.

PMID- 23964460
TI  - Antimicrobial activity of Thai medicinal preparation of Khampramong Temple used
      for cancer treatment and its plant components.
AB  - BACKGROUND: Thai medicinal preparation of Khampramong Temple has been used for
      cancer treatment more than ten years ago. It is composed of eleven herbs. Many
      anticancer drugs exhibited antimicrobial activity as antitumor antibiotics such
      as the anthracycline group [daunorubicin] and quinone group [mitomycin C].
      OBJECTIVE: To determine antimicrobial activity of Thai medicinal plants used to
      treat cancer patients of Khampramong Temple by disc diffusion and agar dilution
      methods. MATERIAL AND METHOD: The extraction procedure was maceration method
      using 95% ethanol and drying by evaporator In the preliminary study, all extracts
      were evaluated for antimicrobial activity by disc diffusion method against two
      strains of Gram positive bacteria (Staphylococus aureus and Bacillus subtilis),
      one Gram negative bacteria (Escherichia coli) and one fungus (Candida albicans).
      The active plant extracts were diluted to determine the minimum inhibitory
      concentration (MIC) by agar dilution method. RESULTS: The preparation showed
      antimicrobial activity against S. aureus, B. subtilis and E. coli (MIC = 1.25,
      0.625 and 5 mg/ml, respectively) but no inhibition against Candida albicans. Most
      extracts showed activity against B. subtilis and Rhinacanthus nasutus extract
      showed the highest antimicrobial activity (MIC = 0.156 mg/ml). Hydnophytum
      formicarum Jack, Tectona grandis L.f and Salacia chinensis L. exhibited good
      antibacterial activity against S. aureus (MIC = 1.25, 0.15625 and 0.3125 mg/ml
      respectively). CONCLUSION: These results supported the use of this preparation on
      chronic wound infection of cancer patients and the antimicrobial compounds of the
      preparation should be further studied to be used in cancer patients.

PMID- 23964461
TI  - Effects of mirror neurons stimulation on motor skill rehabilitation in children
      with cerebral palsy: a clinical trial.
AB  - OBJECTIVE: The authors aimed to compare the motor function measured by Gross
      Motor Function Measure (GMFM-66) between mirror neurons stimulation based VCD
      program at home and conventional physical therapy in children with cerebral palsy
      for two months. MATERIAL AND METHOD: A randomized controlled trial was performed
      with thirty children with spastic diplegia aged 2-10 years in Thammasat
      university hospital and Rajanukul institue. They were randomly assigned to
      receive either the mirror neurons stimulation based VCD program practice at home
      (experimental group) or the conventional physical therapy (control group) for two
      months. Both groups were measured the motor function by GMFM-66 at entry, the
      first month and the end of the second month. Analysis of covariance was used to
      compare mean changes of GMFM-66 scores between both groups at the second month
      after adjusted for the baseline level. RESULTS: A total of 30 children with
      cerebral palsy, aged 2.2-9.5 years (mean age 5.9 +/- 2.2 years). The mean changes
      of the GMFM scores in experimental group were slightly higher than those in the
      control group of 2.1 (95% CI: -2.3, 6.5) at the second month after adjusted for
      the baseline level. The mean GMFM scores were significantly improved in all
      dimensions except lying and rolling dimension, at the first and second month when
      compared to the baseline level in both groups. CONCLUSION: This pilot study
      demonstrated the mirror neurons stimulation based VCD program can improve motor
      function, at least, as much as the conventional physical therapy.

PMID- 23964462
TI  - Chronological production of thioacetamide-induced cirrhosis in the rat with no
      mortality.
AB  - BACKGROUND: Cirrhotic animal models are useful in studying complications of
      chronic liver disease. The authors chronologically investigated the effect of
      thioacetamide (TAA), administered intraperitoneally and adapted individually to
      weight changes, focusing on the optimal moment to obtain typical features of
      cirrhosis. MATERIAL AND METHOD: Male Wistar Rats,150-200 g, were intoxicated
      three times per week with TAA of 200 mg/kg for 4, 8, 12 or 16 weeks (n = 8 per
      group), respectively and compared with age-matched controls (n = 4 per group).
      The individual body weight and liver function test were also measured in each
      group. Liver samples from each group were histologically stained with Sirius red
      in order to identify the degree of liver fibrosis. RESULTS: Rats intoxicated for
      4, 8, 12 or 16 weeks had no mortality and histologically showed hepatitis and
      advanced fibrosis. At 12 and 16 weeks, all animals showed macronodular cirrhosis
      with signs of high-grade hepatocellular dysplasia. The weight of the treated
      groups at different time points was significantly lower than the controls.
      Routine liver function tests between cirrhotic and control rats showed
      significantly higher only in alanine transaminase (ALT) and aspartate
      aminotransferase (AST) at 8 and 12 weeks. However in the cirrhotic rats at 16
      weeks, the ALT and AST were much lower than that at 8 and 12 weeks but did not
      show any difference from the controls. CONCLUSION: Thioacetamide, adapted to
      individual weight changes, leads to a model of cirrhosis in the rat at 12 and 16
      weeks with zero mortality.

PMID- 23964463
TI  - Activated Ito cells of cirrhotic liver express M3 muscarinic receptor after
      thioacetamide exposure.
AB  - Ito cells or perisinusoidal stellate cells or hepatic fat storing cells are
      pericytes of normal liver sinusoidal endothelial cells. Activation of Ito cells
      by chemicals or toxins causes transdifferentiation into the main collagen
      producing cells involving in the progression of liver cirrhosis. Quantitative
      analysis of Ito cell activation by immunohistochemistry has been shown to be
      useful in predicting the rate of progression of liver fibrosis in some clinical
      situations. The present study demonstrated that the activated Ito cells in
      thioacetamide-induced cirrhotic liver which were immunopositive with alpha smooth
      muscle actin, expressed M3 muscarinic receptor but not M1, M2, M4 and M5. These
      findings suggest that the M3 muscarinic receptor might involve in triggering
      intracellular signalling pathways in activated Ito cell to produce collagen
      fibers and may be of future interest in hepatic fibrosis therapy.

PMID- 23964464
TI  - Recurrent eccrine poroma with malignant transformation and bony involvement of
      the foot: a case report and review of the literature.
AB  - OBJECTIVE: Eccrine poroma is a benign appendage tumor showing either eccrine or
      apocrine differentiation. However malignant transformation of this tumor is very
      rare. The present report demonstrated a case of the eccrine poroma with malignant
      transformation and its rarity in terms of its high degree of recurrences and its
      aggressiveness with bony invasion. CASE REPORT: A 67-year old female had a mass
      on plantar surface of 4th-5th intermetatarsal area of her left foot for 10 years
      with three recurrent episodes following excisions at local hospital with no
      pathological report. She was referred to our institute. A recurrent tumor was
      removed again with pathological findings as eccrine poroma with incomplete
      excision; however; the patient had a failure to follow-up. Four years later; she
      was back in our center again with 5th episode of recurrent tumor which was
      marginally excised with pathological findings revealing a malignant
      transformation of eccrine poroma with close resected margins. Unfortunately, the
      patient failed to follow-up again. Eventually, four years later she returned to
      our institute with 6th recurrent episode of tumor. Incisional biopsy was
      performed with pathological findings as appendage tumor with eccrine
      differentiation. Wide resection including removal of 5th metatarsal head-and-neck
      was performed due to aggressive behaviors of this tumor; particularly; history of
      malignant findings and multiple recurrences, significantly bony invasion. Final
      pathologicalfindings were malignant eccrine poroma with close resected margin.
      There were no metastases in evidence from all investigations. Local irradiation
      with the aim of eradication of microscopically residual tumor was initiated.
      CONCLUSION: Malignant transformation is a rare occurrence of eccrine poroma. It
      should be initially included in differential diagnoses, especially in a patient
      with long standing foot lesion or history of recurrent masses. Wide excision is
      recommended as basis treatment, especially in a patient with high likelihood of
      recurrences or positive malignant transformation.

PMID- 23964465
TI  - Perinatal lethal osteogenesis imperfecta in a Thai newborn: the autopsy and
      histopathogical findings.
AB  - Osteogenesis imperfecta (OI) is an inherited disorder of type I collagen
      synthesis with an estimate incidence of I in 100,000 live births. Among all
      types, OI type II is the most severe type with perinatal death. The authors
      describes a male neonate with characteristic features of osteogenesis imperfect
      type II, including short crumpling limbs, beaded ribs, poorly bony ossification
      and blue sclera. Autopsy with histological study revealed not only multiple
      fractures, but pulmonary hypoplasia and intracerebral hemorrhages were also
      present. Both are the leading causes of death in the lethal type OI patients.

PMID- 23964466
TI  - Elastofibroma: a rare case report and review of the literature.
AB  - Elastofibroma is an uncommon fibroelastic tumor-like lesion which usually
      presents in a characteristic area between the lower portion of the scapula and
      the chest wall, lying deep to the latissimus dorsi and rhomboid major muscles. It
      appears almost exclusively in elderly individuals and is associated with history
      of repetitive tissue injuries. It has pathognomonic histopathologic findings.
      Although the lesion has previously been defined as a reactive process, its true
      etiology remains unknown. Based on clinical manifestations and correlation with
      imaging studies, a presumptive diagnosis of elastofibroma can be made in order to
      avoid an unnecessary surgery. Here we report a case of elastofibroma in a typical
      location and present a review of the literature behind its pathogenesis.

PMID- 23964467
TI  - [Specialised palliative home care (SAPV) in an urban setting--a first year
      experience].
AB  - PROJECT DESCRIPTION: The Palliative Home Care Team of the
      InterdisciplinaryCenterfor Palliative Medicine at Munich University Hospital has
      been providing Specialized Home Palliative Care (German abbreviation: SAPV)
      according to the new German regulations since October 2009. RESULTS: Out of 267
      requests, 178 patients were accepted for SAPV, 33 thereof at the level of care
      coordination and 140 as partial or total home palliative care including 24-h, 7/7
      on-call duty. Of the latter group, 90 died at home, 19 in a palliative care unit
      or hospice and one on a hospital ward.The place of death corresponded to the
      patients' wishes in 98% of cases. Altogether, emergency medical services other
      than the SAPV team were called upon in 7 cases, and 12 patients were admitted to
      a general hospital ward. More than a quarter of our patients had non-oncological
      diagnoses.The proportion of work dealing with family members (21%) was higher
      than the patient-related one (19%). The highest percentage (37%) represented
      office work. CONCLUSIONS: The requirement for SAPV in the urban setting is high,
      in spite of the intensive primary care, with an increasing proportion of non
      oncological patients. A key aspect concerns the work with family members. SAPV
      can minimize the number of hospital admissions and emergency calls. The patient's
      wishes concerning the place of death can be fulfilled. Feed-back from patients
      and family members indicates that SAPV makes an important contribution towards
      removing the taboo associated with death and dying.

PMID- 23964468
TI  - [Naturopathic and orthopaedic in-patient treatment of chronic back pain--a
      comparison study].
AB  - BACKGROUND: This study compares orthopaedic and naturopathic inpatient treatment
      concepts for back pain with regards to therapeutic efficacy. PATIENTS AND
      METHODS: A controlled prospective cohort study is presented. 187 conservatively
      treated patients of an orthopaedic clinic and 161 patients of a clinic for
      naturopathy were recruited for the study, if they needed inpatient treatment
      because of chronic back pain.The results were measured with the Oswestry Score
      for orthopaedic symptoms as primary endpoint and the SF-36 for life quality
      before treatment (T0), after 3 (T2) and 6 months (T3), plus the SES for pain
      intensity and pain quality (T0, T1 = at discharge, T2, T3). Accompanying diseases
      were documented with anamnesis and catamnesis sheets. The whole collectives were
      evaluated. Additionally a gender specific analysis was performed. RESULTS: For
      the main and secondary objectives no differences between the naturopathic and
      orthopaedic treatment groups (screened patients with back pain for naturopathy
      286, 187 for orthopedics, in the study included patients 161 respectively 140
      after 2 weeks, 62 respectively 68 after 6 months; mean age 57.1 respectively 54.0
      years, female 85.1 respectively 63.6%) could be verified (Oswestry Score at T0:
      43.0, 95%-confidence-interval 39.6-45.3; at T2: 40.7, 95%-confidence-interval
      37.4-44.0). Only in the subgroup of women, who account for 86% of the
      naturopathic patients, a difference in the main objective (Oswestry Score) was
      found (p = 0.014) in favour of naturopathy (T2: 32.6, 95%-confidence-interval
      24.9-40.2) compared to orthopedics (T2: 45.1,95%-confidence-interval 41.2-49.1).
      CONCLUSION: Treatment results of naturopathic, complex" inpatient treatment of
      chronic back pain are comparable to conventional orthopaedic treatment at all
      points of time T1 to T3. The study design does not allow the conclusion, that the
      therapeutical concept can be changed forthetwo groups of patients with the same
      chance of good therapeutical efficacy. The result of the study is limited in this
      respect as the therapeutic effect cannot be claimed to be the same if the
      treatment groups were exchanged. Thus the improvement is only comparable.

PMID- 23964469
TI  - [Treatment of type 2 diabetes mellitus--which role do GLP-1 receptor agonists
      play?].
AB  - The results of the ACCORD-, ADVANCE- and VADT- and further recent studies raised
      doubts regarding whether the guidelined therapy of type 2 diabetes mellitus,
      which aims at achieving HbA1c values of < 6.5%, is always beneficial. The higher
      rate of severe hypoglycemia and weight gain under intensive glycemic control has
      raised debates of whether the current guidelines should be adopted accordingly.
      Modern state-of-the-art treatment should consider: a) early treatment start, b)
      sustained blood sugar decrease, and c) simultaneously prevention of hypoglycemia
      and weight gain, d) prevention of little investigated multiple glucose-lowering
      agents, e) easy handling and easy to be integrated into daily schedules. The
      present work reviews current options with regard to these requirements with
      special focus on the new GLP-1 receptor agonists.

PMID- 23964470
TI  - [Treatment of myofascial pain syndrome (MPS) with botulinum toxin type A (BoNT
      A)].
AB  - BACKGROUND: Myofascial pain syndrome (MPS) is characterised by acute and chronic
      pain of the muscles and neighbouring tendons and fasciae. A chronification of the
      symptoms can take place quite rapidly or develop over years, depending on the
      individual disposition. Since the mid-nineties, the treatment of MPS with
      botulinum toxin A (BoNT-A) has gained more importance, especially in cases where
      conservative therapies were not efficient. METHODS: In this single centre
      observation, 384 patients with chronified MPS were analysed. Inclusion criteria
      were previous unsuccessful conventional therapies and a disease and pain duration
      of at least 6 months. One vial with 500 units BoNT-A (Dysport) was applied with
      the injection points chosen individually for each patient. Effectiveness of the
      therapy was assessed on the basis of change in pain intensity as measured on a 10
      cm gradual Visual Analogue Scale (VAS). The pain pressure threshold was also
      determined for 227 patients. RESULTS: One week after injection, pain intensity
      was reduced for nearly half of the patients (47.4%) by more than 2 score points
      versus baseline. This percentage increased to 86.1% of the patients up to the
      next visit six weeks after treatment. Six weeks after injection, a decrease of
      pain intensity could be observed in 368 of the 384 patients (95%). Only 11
      patients judged their pain intensity as unchanged or even worse.The pain
      pressurethreshold increased bya median value of 0.6 (pt < 0.001) from one week
      after treatment up to the last visit 6 weeks following treatment. CONCLUSION:
      BoNT-A, appropriately administered, is an effective and safe therapy option in
      the treatment of MPS. For the effective treatment of MPS, concomitant
      physiotherapy with different therapeutical options must be applied in order to
      compensate for muscular imbalances.

PMID- 23964471
TI  - [Individual risk screening and visualization as a central element of health days
      through the interactive electronic GloRiA program].
AB  - BACKGROUND: Health days are an established forum for prevention and health
      promotion for different groups in the general population. Through the use of
      modular questionnaires "Global Risk Assessment" (GloRiA) on computers (handheld
      and desktop), the recording of patient data and presentation of the results can
      be optimized. Possible applications include identification of risk factors, early
      detection of patients at risk, epidemiology and health services research,
      promotion of patient adherence by visualizations (e.g. risk scores). Up to 12
      different question modules are available (e.g. risk for the occurrence of
      cardiovascularevents by Framingham score, forfuture riskof diabetes mellitus
      using FindRisk score, smoking, COPD, pain, comorbidities). METHODS AND RESULTS:
      During 57 health days in 2010 and 2011, data were collected from 3451 persons
      (53% women, mean age 59.6 +/- 15.4 years) using GloRiA. The percentage of former
      smokers was 32.7%, while that of current smokers was 14.7%. The average 10-year
      risk based on the Framingham score (calculated with 1739 persons) in 53.7% of
      respondents was at <10%, in 37.0% at 10-20%, and in 9.3% at > 20%. In men risk
      was higher than in women. Smoking cessation would theoretically reduce the mean
      10-year risk from 10.9 +/- 9.2% to 7.4 +/- 6.6%. In 50.5% of participants blood
      pressure measurement revealed elevated values, and in 10% or 2%, respectively, a
      moderately high or high 10-year riskof incident diabetes mellitus according to
      FindRisk. CONCLUSION: The use of GloRiA for the consolidation of health data
      under the framework of health days provides new and sustained possibilities in
      early detection of cardiovascular disease. The calculation and visualization of
      risks and the impact of treatment decisions, e.g. reduction of cardiovascular
      risk by smoking cessation, were communicated directly to the participants. The
      individual health report facilitates the diagnostic procedures bya physician.

PMID- 23964472
TI  - [Vitamin D deficiency in Germany, is it a danger for increased morbidityand
      mortality?].
AB  - Vitamin D regulates the calcium-phosphate metabolism and thereby plays an
      important role for the integrity and functioning of bone, muscle and nerves.
      Studies have shown furthermore an influence on certain types of cancer, diabetes
      and cardiovascular diseases. Vitamin D is mainly produced by the skin. During
      exposure to sunlightthe precursor7-dehydrocholesterol is transformed to
      colecalciferol (vitamin D3). Smaller amounts are supplied by nutrition. In our
      latitude vitamin D synthesis takes only place during summertime. The vitamin
      stored in fat tissue in generally is not sufficient for the whole winter period
      and accordingly insufficiency is very frequent. In a cross-sectional study all
      over Germany (DeViD, 2007) only about 8% of the population was vitamin D
      sufficient in spring time.Two prospective studies (2008) proved a correlation
      between vitamin D supply and overall mortality. An amelioration of vitamin D
      supply can be achieved either by increasing sun exposure or daily oral intake of
      800-2000 IU (=20-50 microg) colecalciferol.

PMID- 23964473
TI  - [Use of St. John's Wort for depression in primary care - a non-interventional
      study].
AB  - BACKGROUND: Mild to moderate depression is frequently treated by general
      practitioners in Germany, quite often with St. John's Wort preparations. In
      contrast, controlled clinical trials were usually performed in psychiatric
      specialist centers or hospitals. METHODS: In this one-armed, prospective non
      interventional study 408 general practitioners documented 1300 patients with mild
      or moderate depression, which received 600 mg St. John's Wort extract WS 5570
      once daily. The observation period was 8 to 10 weeks. Therapeuticeffectand
      tolerabilityof WS 5570 were investigated. Additionally, doctors were asked for
      their experienceswith and attitudes to depression therapy and complementary
      medicine, reasons for administration of St. Johns Wort and its contribution
      totreatmentsuccess. RESULTS: 807 patients, who were included in the analysis
      corresponding to the protocol, had rates for successful treatment (> 50% decrease
      of the Hamilton 17-item depression scale [HAMD]) 79,3%, respectively for
      remission 68,4%. Six patients (0.46%) dropped out for adverse drug reactions. For
      comparison with the results of an earlier controlled clinical study (WS 5570 600
      mg/d vs. 1200 mg/d vs. placebo), which was conducted mainly by medical
      specialists, 257 patients complying with the inclusion criteria of the controlled
      study were analysed. HAMD-scores at entry (22.9) and improvement after 2 (-6.6)
      and 6 weeks (-10.8) were very similar to those reported in the controlled
      clinical trial. 202 evaluable questionnaires completed by 408 doctors were
      available. Doctors regarded self-healing and placebo effects as important
      therapeuticfactors; however, in 75% of the cases they assigned at least 50% of
      treatment success to the St. John's Wort preparation, and in 19% it was regarded
      as the only reason for improvement. CONCLUSIONS: General practitioners consider
      St. John's Wort extract WS 5570 a well tolerable therapeutic instrument
      contributing more than 50% to total treatment effect. Causal conclusions to the
      efficacy of WS 5570 cannot be drawn in this study because of the non
      interventional design. Efficacy of treatment of mild to moderate depression in
      primary care is comparable to findings in specialist-based controlled clinical
      studies.

PMID- 23964474
TI  - [Acetaminophen - A modern classic under suspicion].
AB  - Paracetamol is one of the most popular and widely used drugs for the treatment of
      pain and fever and provides safe and effective relief of these symptoms since
      decades. The mechanism of action is very complex and involves the inhibition of
      the peroxidase portion of the cyclooxygenase enzyme together with the modulation
      of the serotoninergic and cannabinoid system. Paracetamol is a safe drug, if used
      in accordance with the regulations and has demonstrated a superior side effect
      profile to many widely used NSAIDs.

PMID- 23964475
TI  - [Acetaminophen and the liver: damage at therapeutic dose levels?].
AB  - The possibility of liver intoxication at therapeutic doses of paracetamol
      (maximal dailydose of 4 x 1 g) is supported by retrospective, but not by
      controlled prospective studies. Intended orsuicidal overdosages are frequently
      misjudged in retrospektive reports. Malnutrition, ethanol consumption, and drugs
      inducing hepatic metabolism are no established riskfactors at therapeutic dose
      levels. Dose adaptation in existing liver disease is recommended for longer-term
      use.Transient increases in transaminase values (> 3 x upper limits of normal)
      after regulardoses of paracetamol are not proof of hepatic damage unless
      associated with corresponding symptoms or laboratory changes indicative of
      compromised hepatic function (total bilirubin, INR). There is insufficient
      evidence of liver injury by paracetamol at regular dose levels.

PMID- 23964476
TI  - Individual differences in perceived elevation and verticality: evidence of a
      common visual process.
AB  - Thel frontoparallel orientation of a long peripheral line influences two visual
      norms, elevation, also called the visual perception of eye level (VPEL), and
      orientation in the frontoparallel plane, called visually perceived vertical
      (VPV). However, VPEL and VPV are distinct in that different integration rules
      describe the combinatorial effects of two lines symmetrically located on opposite
      sides of the median plane. Nevertheless, we propose that the same orientation
      sensitive process underlies the two discriminations. We measured the two norms
      while we manipulated visual orientation with 1-line and 2-line stimuli (on
      opposite sides of the median plane), then modeled the large and significant
      effect of line orientation on VPEL and VPV settings as linear averages of signals
      from vision and from non-visual, body-referenced, vestibular and proprioceptive
      mechanisms. Significant correlations are evident between observers (n = 30) in
      the effect of visual orientation on both VPEL and VPV, and in the baseline
      measures (dark value, intercept) on both norms. The latter egocentric bias is
      further discussed in the context of the operation of the body-referenced
      mechanism across different egocentric discriminations for an individual subject.
      Given the evidence for different integration rules, the pattern of individual co
      variation implies the existence of a single, shared visual orientation process
      that feeds to separate integration processes.

PMID- 23964477
TI  - Color signal integration for color discrimination along a long-range apparent
      motion trajectory.
AB  - In contrast to the classical view that fundamental visual attributes such as
      color and motion are independently processed in the visual system (e.g.
      Livingstone and Hubel, 1987; Marr, 1982), recent studies have revealed various
      forms of cross-attribute interactions, such as averaging of color appearance
      along the motion trajectory of an object (Nishida et al., 2007). In this study,
      we investigated whether such color signal integration along a motion trajectory
      can be induced only by motion mechanisms having large receptive fields, without
      simple integration within direction-selective neurons with small receptive
      fields, like those in V1. The stimulus consisted of discs with long-range
      apparent motion along a circular trajectory. The stimulus onset asynchrony (SOA)
      between disc presentations controlled the strength of the apparent motion
      perception. We measured observers' sensitivity in detecting color modulation on
      the discs. The results showed that the measured sensitivity was lowest at SOAs
      corresponding to the strongest motion perception. This can be interpreted as
      follows: color signals were integrated along an apparent motion path, and this
      integration reduced chromatic sensitivity by averaging color signals. Another
      experiment that controlled apparent motion perception in a different way also
      supported this idea. However, this integration effect seemed to be linked to
      responses of motion detectors for the apparent motion stimuli, not directly to
      perceptual motion representation in the visual system. These results suggest that
      the human visual system handles color information from retinal inputs regarding
      moving objects based not only on a retinotopic coordinate but also on object
      based coordinates, even when the moving object yields only long-range apparent
      motion.

PMID- 23964478
TI  - Virtual swimming--breaststroke body movements facilitate vection.
AB  - Visually induced illusory self-motion (vection) was facilitated by active
      breaststroke arm and body movements. Optic flow was generated by having the
      standing observer make these arm movements, which were detected by Kinect and
      incorporated into the display. When generated, this optic flow was either
      expanding (i.e. congruent with the observer's head motion) or contracting (i.e.
      incongruent with his/her head motion). Optic flow generated during these active
      movement conditions was also later played back to the observer during passive
      viewing conditions. On each of these trials, we recorded vection strength
      (latency, duration and magnitude). We found that: (i) both congruent and
      incongruent breaststroke movements increased vection (i.e. compared to passive
      viewing conditions); and (ii) congruent breaststroke movements increased vection
      more than incongruent ones. We name the enhancement provided by this type of
      active movement 'virtual swimming'. This demonstration shows that even unusual
      body movements can function as a self-motion signal.

PMID- 23964479
TI  - Separate presentation of additional accelerating motion does not enhance visually
      induced self-motion perception.
AB  - It has been repeatedly reported that visual stimuli containing
      ajittering/oscillating motion component can induce self-motion perception more
      strongly than a pure radial expansion pattern. A psychophysical experiment with
      11 observers revealed that the additional accelerating components of the visual
      motion have to be convoluted with the motion of the main-axis to facilitate self
      motion perception; additional motion presented in an isolated fashion impairs the
      perception of self-motion. These results are inconsistent with a simple
      hypothesis about the perceptual mechanism underlying the advantage of
      jitter/oscillation, which assumes that the accelerating component induces an
      additional self-motion independently of the main motion at the first stage, and
      then the two self-motions induced by the main motion and the additional component
      become integrated.

PMID- 23964480
TI  - International Multisensory Research Forum 2012 meeting special issue.

PMID- 23964481
TI  - Early interaction between vision and touch during binocular rivalry.
AB  - Multisensory integration is known to occur at high neural levels, but there is
      also growing evidence that cross-modal signals can be integrated at the first
      stages of sensory processing. We investigated whether touch specifically affected
      vision during binocular rivalry, a particular type of visual bistability that
      engages neural competition in early visual cortices. We found that tactile
      signals interact with visual signals outside of awareness, when the visual
      stimulus congruent with the tactile one is perceptually suppressed during
      binocular rivalry and when the interaction is strictly tuned for matched visuo
      tactile spatial frequencies. We also found that voluntary action does not play a
      leading role in mediating the effect, since the interaction was observed also
      when tactile stimulation was passively delivered to the finger. However,
      simultaneous presentation of visual and tactile stimuli is necessary to elicit
      the interaction, and an asynchronous priming touch stimulus is not affecting the
      onset of rivalry. These results point to a very early cross-modal interaction
      site, probably V1. By showing that spatial proximity between visual and tactile
      stimuli is a necessary condition for the interaction, we also suggest that the
      two sensory spatial maps are aligned according to retinotopic coordinates,
      corroborating the hypothesis of a very early interaction between visual and
      tactile signals during binocular rivalry.

PMID- 23964482
TI  - Cross-correlation between auditory and visual signals promotes multisensory
      integration.
AB  - Humans are equipped with multiple sensory channels that provide both redundant
      and complementary information about the objects and events in the world around
      them. A primary challenge for the brain is therefore to solve the 'correspondence
      problem', that is, to bind those signals that likely originate from the same
      environmental source, while keeping separate those unisensory inputs that likely
      belong to different objects/events. Whether multiple signals have a common origin
      or not must, however, be inferred from the signals themselves through a causal
      inference process. Recent studies have demonstrated that cross-correlation, that
      is, the similarity in temporal structure between unimodal signals, represents a
      powerful cue for solving the correspondence problem in humans. Here we provide
      further evidence for the role of the temporal correlation between auditory and
      visual signals in multisensory integration. Capitalizing on the well-known fact
      that sensitivity to crossmodal conflict is inversely related to the strength of
      coupling between the signals, we measured sensitivity to crossmodal spatial
      conflicts as a function of the cross-correlation between the temporal structures
      of the audiovisual signals. Observers' performance was systematically modulated
      by the cross-correlation, with lower sensitivity to crossmodal conflict being
      measured for correlated as compared to uncorrelated audiovisual signals. These
      results therefore provide support for the claim that cross-correlation promotes
      multisensory integration. A Bayesian framework is proposed to interpret the
      present results, whereby stimulus correlation is represented on the prior
      distribution of expected crossmodal co-occurrence.

PMID- 23964483
TI  - Evaluation of surgically assisted rapid maxillary expansion and orthodontic
      treatment. Effects on dental, skeletal and nasal structures and rhinological
      findings.
AB  - Surgically Assisted Rapid Maxillary Expansion (SARME) is frequently used to treat
      skeletal maxillary transverse deficiency (MTD) in skeletally mature and non
      growing individuals. Despite previous research in the field, questions remain
      with respect to the long-term stability of SARME and its effects on hard and soft
      tissue. The overall aim of the present doctoral work was to achieve a greater
      understanding of SARME, using modern image technology and a multidisciplinary
      approach, with special reference to effects on the hard and soft tissues and
      respiration. A more specific aim was to evaluate the long-term stability in a
      retrospective sample of patients treated with SARME and orthodontic treatment and
      to compare the results with a matched, untreated control group. The studies in
      this doctoral project are thus based on two different samples and study designs.
      The first sample, Study I (Paper I), is a retrospective, consecutive, long-term
      follow-up material of study models from 31 patients (17 males and 14 females)
      treated with SARME and orthodontic treatment between 1991 and 2000. The mean pre
      treatment age was 25.9 years (SD 9.6) with a mean follow-up time of 6.4 years (SD
      3.3). Direct measurements on study models were made with a digital sliding
      caliper at reference points on molars and canines. To evaluate treatment outcome
      and long-term stability, the results were compared with study models from an
      untreated control group, matched for age, gender and follow-up time. The second
      sample, Study II (Papers II-IV), is a prospective consecutive, longitudinal
      material of 40 patients scheduled to undergo SARME and orthodontic treatment
      between 2006 and 2009. In Paper II, one patient was excluded because of a planned
      adenoidectomy. The final sample comprised 39 patients (16 males and 23 females).
      The mean age at treatment start was 19.9 years (range 15.9 - 43.9). Acoustic
      rhinometry, rhinomanometry and a questionnaire were used to assess the degree of
      nasal obstruction at three time-points; pre-treatment, three months after
      expansion and after completed treatment (mean 18 months). In Papers III-IV, three
      patients declined to participate and two had to be excluded because their CT
      records were incomplete. The final sample comprised 35 patients (14 males and 21
      females). The mean age at treatment start was 19.7 years (range 16.1 - 43.9).
      Helical CT-images were taken pre treatment and eighteen months' post-expansion.
      3D models were registered and superimposed at the anterior cranial base. The
      automated voxel-based image registration method allows precise, accurate
      measurements in all areas of the maxilla. In Papers II-IV, the treatment groups
      constituted their own control groups. The main findings in the retrospective,
      long-term follow-up study were that SARME and orthodontic treatment normalized
      the transverse discrepancy and was stable for a mean of 6 years post-treatment.
      Pterygoid detachment did not entirely eliminate the side effect of buccal tipping
      of the posterior molars. Relapse is time-related and is most pronounced during
      the first 3 years after treatment. Thus the retention period should be extended
      and should be considered for this period. The main rhinological findings in the
      prospective longitudinal study were that SARME had a short-term, favourable
      effect on nasal respiration, but the effect did not persist in the long-term.
      However, subjects with pretreatment nasal obstruction reported a lasting
      sensation of improved nasal function. SARME and orthodontic treatment had a
      significant but non-uniform skeletal treatment effect, with significantly greater
      expansion posteriorly than anteriorly. The expansion was parallel anteriorly but
      not posteriorly. The lateral tipping of the posterior segment was significant,
      despite careful surgical separation. No correlation was found between tipping and
      the patient's age. Furthermore, SARME and orthodontic treatment significantly
      affected all dimensions of the external features of the nose. The most obvious
      changes were at the most lateral alar-bases. The difference in lateral
      displacement profoundly influenced the perception of a more rounded nose. There
      were no predictive correlations between the changes. Patients with narrow and
      constrained nostrils can benefit from these changes with respect to the
      subjective experience of nasal obstruction. It is questionable whether an alar
      cinch suture will prevent widening at the alar-base. The 3D superimposition
      applied in Study II is a reliable method, circumventing projection and
      measurement errors. In conclusion, SARME and orthodontic treatment normalize the
      transverse deficiency, with long-term stability. SARME has a favourable effect on
      the subjective perception of nasal respiration. SARME significantly affects
      dental, skeletal and nasal structures.

PMID- 23964484
TI  - [The nodule hurts more and more... Deep venous thrombosis].

PMID- 23964485
TI  - [Is the chronic patient becoming "exotic"?].

PMID- 23964486
TI  - [Proof of qualification also possible without colloquium].

PMID- 23964487
TI  - [Excellence in continuous research. MMW medication award for sitagliptin].

PMID- 23964488
TI  - [Emergencies in the sky are mostly minor. "Is there a doctor on board"?].

PMID- 23964489
TI  - [Interview with Dr. med. Edgar Buhrle about emergency care in the sky. Physicians
      must identify themselves (interview by Dr. Robert Bublak)].

PMID- 23964490
TI  - [Getting to the root of diabetes. Successful weight loss with telemedicine,
      coaching and protein supplements].

PMID- 23964491
TI  - [Type 2 diabetic patients. 2 larger meals are better than many small ones].

PMID- 23964492
TI  - [Children in the "Muckibude". In strength training the risk of overtraining is
      minimal (interview by Dr. Elke Oberhofer)].

PMID- 23964493
TI  - [My patient suddenly collapsed. Epilepsy or cardiogenic syncope?].

PMID- 23964494
TI  - [Preventive colonoscopy saves lives. An initiative for better acceptance].

PMID- 23964495
TI  - [Your patient needs antithrombotic drugs, 7. Averting the risk of stroke: with
      whom and how?].

PMID- 23964496
TI  - [To all high school seniors considering medical education: better chose an
      alternative medicine practitioner or veterinary career!].

PMID- 23964497
TI  - [Blue vapor with immediate sequelae].

PMID- 23964498
TI  - [What is the role of the prefrontal cortex in suicide?].

PMID- 23964499
TI  - [Obesity in childhood and bronchial asthma].

PMID- 23964500
TI  - [Statins can damage muscles and joints].

PMID- 23964501
TI  - [Normal findings after expensive diagnosis].

PMID- 23964502
TI  - [Red melanoma].

PMID- 23964503
TI  - [Do affective disorders and anxiety disorders have an effect on the stomach?].

PMID- 23964504
TI  - [New local therapies in lung cancer].

PMID- 23964505
TI  - [Minimally invasive surgery for the treatment of lung cancer--indications].

PMID- 23964506
TI  - [Highly conformal radiotherapy of primary and secondary lung malignancies].

PMID- 23964507
TI  - [Emergency checklist: management of epistaxis].

PMID- 23964508
TI  - [Young female: I permanently suffer from bladder infection].

PMID- 23964509
TI  - [Update: clinical lipidology].

PMID- 23964510
TI  - [Diabetes in old age--risk by over- and undertreatment].

PMID- 23964511
TI  - [Springer Medicine director Harm van Maanen on medical specialty media in
      transition and the new digital alignment of his organization. "With the new media
      readers gain significant additional value" (interview by Wolfgang van den
      Bergh)].

PMID- 23964512
TI  - [Hypertension and coronary heart disease].

PMID- 23964513
TI  - [Antibodies to synthetic fragment 95-123 of the prion protein protect neurons and
      astrocytes from beta-amyloid toxicity].
AB  - Toxic effect of beta-amyloid on brain cells during Alzheimer's disease pathology
      is known to be associated with oxidative stress, intracellular Ca2+ increase in
      neurons and astrocytes and activation of reactive oxygen species production.
      Prion protein is involved in beta-amyloid toxicity. Here we investigated an
      effect of affinity purified antibodies to synthetic fragment 95-123 of the prion
      protein on beta-amyloid induced cell death, Ca(2+)-signal, reactive oxygen
      species production and caspase 3 activation. We have shown that antibodies to
      fragment 95-123 are able to protect neurons and astrocytes from beta-amyloid
      induced cell death with no effect on the intracellular Ca2+ concentration altered
      by beta-amyloid treatment. However, the antibodies significantly reduced Abeta
      induced reactive oxygen species production in astrocytes and decreased caspase 3
      activation in neurons and astrocytes. Thus, induction of antibodies to synthetic
      fragment 95-123 of the prion protein provides a new approach to anti-AD vaccine
      design.

PMID- 23964515
TI  - [Experimental analysis of human specific protein coding open reading frame
      c11orf72].
AB  - Gene c11orf72 (also known as FLJ90834) included in human gene reference list was
      previously predicted on the basis oftranscriptome analysis. We show that c11orf72
      predicted protein coding open reading frame is specific for human genome and that
      it is absent from DNAs of other investigated primate species (chimpanzee,
      macaque). For the first time, we systematically analyzed c11orf72 expression in
      five normal and two cancerous human tissues (testicles, heart, brain, lung,
      bladder, bladder tumor and testicular tumor) and found no transcriptional
      activity there. Promoter of c11orf72, located close to promoter of a housekeeping
      gene NDUFV1, has shown high methylation level, whereas NDUFV1 promoter was almost
      free from methylation. The protein product for cllorf72 was analyzed using
      heterologous expression in human cell lines NT2/D1 (Tera2) and HepG2, in N- and C
      terminal fusion constructs with the fluorescent protein TurboGFP. C11orf72
      protein showed no cytotoxic or promitotic activity and was distributed diffusely
      through the cell. Our data confirm the possibility of gain of new protein-coding
      genes during human evolution due to simple accumulation of point mutations.
      However, we found no evidence for the functional significance of gene c11orf72.

PMID- 23964514
TI  - [Unusual amidation reaction of Asn-containing glycopeptide antibiotics using the
      coupling reagent PyBOP].
AB  - The coupling reagent PyBOP is widely used for the synthesis of different peptides
      and their amides, particularly for carboxamides of glycopeptide antibiotics of
      vancomycin or teicoplanin groups. The amidation reaction of the peptide core of
      the glycopeptide antibiotic eremomycin (I) with highly reactive amines in the
      presence of PyBOP is usually not accompanied by the formation of side products.
      However, the amidation of I with bulky amines (e.g., decyl amine and adamantyl
      amine) in the presence of PyBOP and Et3N or di-(i-Pr)2EtN (pH - 8.5) yielded N
      unsubstituted carboxamide of eremomycin (Ia) as an admixture. The reaction of (I)
      or vancomycin (II) with an excess of PyBOP and Et3N (pH - 8.5) without addition
      of an amine or ammonia gave a mixture of products which contained higher amounts
      of the corresponding N-unsubstituted carboxamides (-20%). The structures of the
      samples of Ia and vancomycin amide (IIa) were proved by 1H NMR and ESI MS methods
      and confirmed by comparing with the authentic samples.

PMID- 23964516
TI  - [Oligo(2'-O-Methylribonucleotides) and their derivatives: IV. Conjugates of
      oligo(2'-O-methylribonucleotides) with minor groove binders and intercalators:
      synthesis, properties and application].
AB  - Conjugates of pyrimidine triplex forming 3'-protected oligo(2'-O
      methylribonucleotides) with minor groove binders (MGB) and triplex specific
      intercalator benzoindoloquinoline (BIQ) at 5'-terminus were synthesized. The
      conjugates formed stable complexes with target dsDNA by simultaneous binding both
      in its minor and major grooves and BIQ intercalation. The dissociation constants
      and thermal stability of the conjugate complexes with model dsDNA corresponding
      to polypurine tract (PPT) of genes nef and pol from HIV proviral genome were
      determined. Conjugation of oligo(2'-O-methylribonucleotides) with MGB and
      intercalator increased the stability of the triple complexes with dsDNA at pH 7.2
      and 37 degrees C. Intercalator introduction accelerates the process of complex
      formation. Dose-dependent arrest of the in vitro transcription was demonstrated
      when a 780 b.p. DNA fragment containing the polypurine tract was transcribed
      under the control of T7 promoter in the presence of different concentrations of
      conjugates of oligo(2'-O-methylribonucleotides) containing MGB and BIQ
      intercalator.

PMID- 23964517
TI  - [Phosphate permease gene as a marker for the specific identification of toxigenic
      fungus Fusarium cerealis].
AB  - We have developed phosphate permease gene sequence-based PCR detection system of
      Fusarium cerealis phytopathogenic fungus. Sequencing and analysis revealed that
      the gene displayed unique polymorphism and could serve to establish phylogenetic
      relations as well as a marker to design specific primers. The specificity assay
      has confirmed the absence of cross reactions with DNAs of closely related
      Fusarium species. The qPCR assay demonstrated the 10 pg detection limit of
      specific DNA per reaction.

PMID- 23964518
TI  - [Synthesis, properties and anti-HIV activity of novel lipophilic 3'-azido-3'
      deoxythymidine conjugates containing functional phosphoric linkages].
AB  - One of the approaches to enhance bioavailability of nucleoside reverse
      transcriptase HIV inhibitors consists in design of their prodrugs based on 1,3
      diacylglycerols, which may simulate nature lipids metabolic pathways promoting
      the improvement of drug delivery to the target cells. Glycerolipidic AZT
      conjugates with different functional phosphoric centers were synthesized by H
      phosphonate technique in the present work. Study of prepared prodrugs sensibility
      to the chemical and enzymatic hydrolysis (in buffer solution and under the
      influence of pancreatic lipase) and also study of their anti-HIV activity on the
      T-lymphoid human MT-4 cells in regarding to virus HIV-1(899A) strain were carried
      out.

PMID- 23964519
TI  - Bmo-miR-9A down regulates the expression of Bm-ase gene in vitro.
AB  - MicroRNAs (miRNAs) are a class of non-protein coding small RNAs of 18-24
      nucleotides in length that regulate expression of genes at post-transcriptional
      levels and play multiple roles in biological processes. Bm-ase plays an important
      role in the course of nerve development of the silkworm, Bombyx mori. Bmo-miR-9a
      is a conservative miRNA. By using target prediction software RNA22 and RNAhybrid,
      we found a target site of Bmo-miR-9a in the 3'UTR of Bm-ase gene. To verify the
      regulation function of Bmo-miR-9a on the expression of Bm-ase gene, a Bmo-miR-9a
      over-expressing vector and Bm-ase 3'UTR fused firefly luciferase gene reporter
      plasmid were constructed, respectively. Then they were used to co-transfect the
      BmN cells. The result showed that luciferase activity in the co-transfected cells
      was suppressed compared with the control. A similar result was obtained when BmN
      cells were co-transfected with artificial synthetic Bmo-miR-9a mimics and Bm-ase
      3'UTR fused luciferase reporter plasmid. These results suggest that Bmo-miR-9a
      can down regulate the expression of Bm-ase gene.

PMID- 23964520
TI  - [Phenothiazine derivatives as enhancers of peroxidase-dependent
      chemiluminescence].
AB  - Some N-alkyl phenothiazines with different ionic groups were studied as enhancers
      of chemiluminescence catalyzed by soybean peroxidase. Phenothiazines carrying
      positive charged groups had no an enhancement ability, whereas phenothiazine
      derivatives with negative charged groups increased significantly an intensity of
      chemiluminescence. Correlation between the enhancement activity ofphenothiazines
      and their ability to enzymatically oxidize by hydrogen peroxide was found. The
      discovery of new enhancers open good perspectives for an improvement of
      sensitivity of analytes determination by chemiluminescent enzyme immunoassay.

PMID- 23964521
TI  - [Synthetic transformations of higher terpenoids. XXX. Synthesis and cytotoxic
      activity of betulonic acid amides with a piperidine or pyrrolidine nitroxide
      moiety].
AB  - The reaction of betulonic acid chloride with 4-amino-2,2,6,6
      tetramethylpeperidine-1-oxyl, 3-amino-2,2,5,5-tetramethylpyrrolidine-1-oxyl and 3
      aminomethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl gave corresponding triterpenoid
      amides. It was found that new derivatives exhibit cytotoxic activity against
      tumor cells CEM-13, U-937, MT-4. CCID50 value for most activity compound--N-[3
      oxolup-20(29)-en-30-yl]-(2,2,6,6-tetramethylpiperidine-4-yl)-1-oxyl--was 5.7-33.1
      microM.

PMID- 23964522
TI  - [Synthesis and biological activity of 2,3-secotriterpene acid mono- and
      diamides].
AB  - Four types of amide (C3; C28; C3-C28) conjugates based on 2,3-seco-18alphaH
      oleanane and 2,3-secolupane mono- and dicarboxylic acids were synthesized. The
      range of diamide derivatives was supplemented with C3-C3' and C28-C28'
      dicondensed amides with two A-secotriterpene backbones educed by reacting
      monocarboxylic A-secoacids with biogenic amino acid lysine. Compounds with
      inhibitory action against herpes virus reproduction (EC50 8.7 and 4.1 McM) were
      found among the synthesized mono- and diamide derivatives containing an ethyl
      beta-alaninate fragment. It has been ascertained that diamide with ethyl-beta
      alaninate fragment combines anti-herpes virus properties and anti-HIV activity
      (EC50 5.1 McM). For active compounds, the maximum non-toxic concentration
      (MNTC)/EC50 ratios ranges from 9.7 to 40.8. The synthesized amide conjugates do
      not exhibit any marked cytotoxic effects against human tumor cell lines
      rabdomiosarcoma RD TE32, A549 lung carcinoma and melanoma MS.

PMID- 23964523
TI  - [Antitumor activity of dihydrobetulonic acid amides in vitro and in vivo].
AB  - Amides with homopiperidinic and piperazinic cycles were synthesized from
      dihydrobetulonic acid which was obtained by dihydrobetulin oxidation. All
      substances have shown high antitumor activity (CCID50 3.5-36.2 microM) in vitro
      in lymphoid (CEM-13, U-937) and monocytic (MT-4) human cell lines. Amides with
      methyl- and ethyl-piperazinic residues don't influence viability of Lung Lewis
      Carcinoma cell in culture and haven't any significant effect to its
      transplantates in C57BL/6 mice. But such amides inhibit efficiently the
      metastatic elaboration in lung of these mice. The antimetastatic activity
      increases followed by the change of aliphatic residue length in piperazinic cycle
      from methyl to ethyl.

PMID- 23964524
TI  - [Synthesis, structure and farmacologycal activity of (7R,8S)-epoxy-(13R,17R)
      trioxolaneabietic acid].
AB  - The synthesis and X-ray diffraction established the structure of (7R,8S)-(see
      text for symbol)-(13R,17R)-trioxolaneabietic acid. Predicted by the computer
      system PASS antineoplastic activity and the ability to induce apoptosis, a
      mechanism of cell death, is correlated with experimentally shown cytotoxic
      activity against malignant cell line MeWo. Results of tests on animals have shown
      that abietic acid and its 9R,11S-epoxy-12R,15R-trioxolane derivative have anti
      inflammatory and antiulcer activity in the absence of adverse effects on animal
      organisms.

PMID- 23964525
TI  - Synthesis and biological evaluation of novel isoxazolo[4,3-e]indoles as
      antibacterial agents.
AB  - The synthesis of a new series of 8-bromo-6-alkyl-1-aryl-6H-isoxazolo[4,3-e]indole
      derivatives is described. All the newly synthesized compounds were screened for
      their antibacterial activity against Escherichia coli HB101, Staphylococcuse
      aureus pathogens (methicillin resistant S. aureus and methicillin susceptible S.
      aureus), Pseudomonas aeruginosa, and Bacillus subtilis; also MIC values of these
      compounds were determined.

PMID- 23964526
TI  - Pyranocoumarins from Zosima absinthifolia (Vent) Link roots.
AB  - Zosima absinthifolia (Vent) Link (Apiaceae) is a perennial herb indigenous to
      Iran. It has been used as a medicinal plant from ancient time in Iran, Turkey and
      Pakistan. In the present work, air-dried and powdered plant roots were extracted
      with n-hexane, dichloromethane and methanol, respectively, using Soxhlet
      apparatus. The dichloromethane extract was subjected to vacuum liquid
      chromatography (VLC) and preparative thin layer chromatography (P-TLC) to yield
      two pyranocoumarins, aegelinol and agasyllin. The antimicrobial assay was
      performed using agar dilution method. The results showed that purified compounds
      have modest to weak antibacterial and antifungal activity.

PMID- 23964527
TI  - [The obtaining and analysis of physiological activity of secreted proteins of
      Noggin family].
AB  - We have developed methods for producing recombinant proteins of Noggin family
      (Noggin1 and Noggin2 of the Xenopus laevis frog) that can interact with BMP
      factors of TGF-beta superfamily. The genetic constructs which allow one to
      effectively obtain Noggin1 and Noggin2 from synthetic mRNA microinjected into
      Xenopus laevis early embryos, as well as in the prokaryotic expression system,
      were generated. The obtained proteins contain three Myc-tag epitopes on their N
      terminus. This allow one to compare the expression levels of Noggin1 and Noggin 2
      constructs, to purify them on the affine immunosorbent and to show the activity
      of Noggin proteins by analyzing their ability to bind BMP4 factor TGF-beta
      surperfamily by co-immunoprecipitation.

PMID- 23964528
TI  - [Evaluation of absorbed dose from kilovoltage cone-beam computed tomography by
      radiotherapy planning system: influence on the radiation therapy for prostate
      cancer].
AB  - Image-guided radiation therapy (IGRT) is increasingly being used in modern
      radiation therapy, and it is now possible to verify a patient's position using
      kilo-voltage cone-beam computed tomography (kV-CBCT). However, if kV-CBCT is used
      frequently, the dose absorbed by the body cannot be disregarded. A number of
      studies have been made on the absorbed dose of kV-CBCT, in which absorbed dose
      measurements were made using a computed tomography dose index (CTDI) or a
      thermoluminescent dosimeter (TLD). Other methods include comparison of the
      absorbed dose between a kV-CBCT and other modalities. These techniques are now in
      common use. However, dose distribution within the patient varies with the
      patient's size, posture and the part of the body to which radiation therapy is
      applied. The chief purpose of this study was to evaluate the dose distribution of
      kV-CBCT by employing a radiotherapy planning system (RTPS); a secondary aim was
      to examine the influence of a dose of kV-CBCT radiation when used to treat
      prostate cancer. The beam data of an on-board imager (OBI) was registered in the
      RTPS, after which modeling was performed. The radiation dosimetry was arranged by
      the dosimeter in an elliptical phantom. Rotational radiation treatment was used
      to obtain the dose distribution of the kV-CBCT within the patient, and the
      patient dose was evaluated based on the simulation of the dose distribution. In
      radiation therapy for prostate cancer, if kV-CBCT was applied daily, the dose
      increment within the planning target volume (PTV) and the organ in question was
      about 1 Gy.

PMID- 23964529
TI  - [Fabrication of a visualization equipment for scattered X-rays in the diagnosis
      domain and proposal of a practical training].
AB  - We have built equipment that can visualize the angle distributions of scattered X
      rays. The main body of the equipment is made of a lead-shielded box 340 mm long,
      300 mm wide and 270 mm high. The collimated X-rays are introduced into the
      equipment from the front face, then scattered by the sample located in the center
      of the equipment. The X-rays scattering toward the upper side are detected by the
      phosphor plate. To verify the usability of the equipment, an experiment using
      diagnostic X-rays was carried out. X-rays with a tube voltage of 100 kV were
      narrowed down to 6 mm(phi) and a 2 mm-thick acrylic sample was irradiated. The
      experimental conditions with a tube current-time product of 300 mAs to 1500 mAs
      proved appropriate for obtaining suitable images on a 10 inch x 12 inch phosphor
      plate. The obtained images were analyzed using ImageJ. The experimental values
      were in good agreement with the theoretical distribution calculated by Klein and
      Nishina. Because the distribution of the scattered X-rays can be visualized in
      relatively simple experiments using the developed equipment, it is hoped that it
      will be of use for the practical training of beginners.

PMID- 23964530
TI  - [Evaluation of the individual tube current setting in electrocardiogram-gated
      cardiac computed tomography estimated from plain chest computed tomography using
      computed tomography automatic exposure control].
AB  - The aim of this study was to estimate the tube current on a cardiac computed
      tomography (CT) from a plain chest CT using CT-automatic exposure control (CT
      AEC), to obtain consistent image noise, and to optimize the scan tube current by
      individualizing the tube current. Sixty-five patients (Group A) underwent cardiac
      CT at fixed tube current. The mAs value for plain chest CT using CT-AEC (AEC
      value) and cardiac CT image noise were measured. The tube current needed to
      obtain the intended level of image noise in the cardiac CT was determined from
      their correlation. Another 65 patients (Group B) underwent cardiac CT with tube
      currents individually determined from the AEC value. Image noise was compared
      among Group A and B. Image noise of cardiac CT in Group B was 24.4 +/- 3.1 HU and
      was more uniform than in Group A (21.2 +/- 6.1 HU). The error with the desired
      image noise of 25 HU was lower in Group B (2.4%) than in Group A (15.2%).
      Individualized tube current selection based on AEC value thus provided consistent
      image noise and a scan tube current optimized for cardiac CT.

PMID- 23964531
TI  - [Trial for power spectrum analysis in various injection timing for contrast
      medium].
AB  - Frequency analysis is a method of measuring the spatial frequency component in
      images. We attempted to analyze and assess frequency analyses of images of
      various contrast medium injection timings using a normalized integral power
      spectrum. In magnetic resonance imaging, the k-space order was linear and
      sequential. During the twenty-second scanning time, we injected contrast medium
      at 3 ml/s and varied the duration of the injection from zero to four seconds,
      four to eight seconds, eight to twelve seconds, twelve to sixteen seconds, and
      sixteen to twenty seconds. We then analyzed the images. The rates of change and
      area values were calculated, and a dendrogram of area value by cluster analysis
      was made. The element of high frequency area's power values rose when the
      contrast medium was in the high-frequency area, and the element of low frequency
      area's power values rose when the contrast medium was in the low-frequency area.
      These data lines crossed at 0.092-0.115 cycles/mm. Five time durations were
      identified: these were a function of rate of change and area value. Frequency
      analysis of injection timing for contrast medium using the normalized integral
      power spectrum can thus be applied; this method can thus be employed as a method
      of examining injection timing for contrast medium and choosing a k-space order of
      optimization.

PMID- 23964532
TI  - [Investigation of radio frequency heating of dental implants made of titanium in
      1.5 tesla and 3.0 tesla magnetic resonance procedure: measurement of the
      temperature by using tissue-equivalent phantom].
AB  - Titanium (Ti) implants are increasingly being used for dental parts. There is no
      problem with the attraction of a static magnetic field for Ti in magnetic
      resonance imaging (MRI), since Ti is paramagnetic. However, there is a risk of
      radio frequency (RF) heat generation within Ti. 3.0 T-MRI scanners are becoming
      increasingly common. The specific absorption rate (SAR) of 3.0 T-MRI is quadruple
      that of SAR compared with 1.5 T-MRI due to its being proportional to the square
      of the strength of a static magnetic field. The effect of heat generation in 3.0
      T-MRI can thus be greater than in 1.5 T-MRI. So, using 1.5 T and 3.0 T-MRI
      scanners, we measured the temperature of several Ti implants using the same
      scanning parameters during MRI scanning. Our measurements showed the rise in
      temperature of the Ti implants to be a maximum of 0.4 degrees C. In this study,
      however, Ti in a human mouth was not directly measured, so we need to attempt to
      perform MRI carefully on patients with Ti implants.

PMID- 23964533
TI  - [Optimized magnetic resonance sequences and parameters with operative assisted
      images for radical prostatectomy at 3 tesla-magnetic resonance image].
AB  - The objective of our study was to optimize magnetic resonance image (MRI)
      sequences and parameters using operative assisted images (three-dimensional
      images) for radical prostatectomy at 3 tesla (T) MRI. Five healthy volunteers
      underwent MRI on the 3.0 T scanner. Various sequences and parameters [Cube (TE/TR
      = 18, 50, 90 ms/2000 ms), FIESTA (TE/TR/FA = 2.4 ms/5 ms/40 degrees, 90 degrees),
      fSPGR (TE/TR/FA = 2.3 ms/11.2 ms/20 degrees), slice thickness = 1.2 mm, matrix =
      192 x 160] were respectively compared. Several structures of the pelvis (the
      central zones and transition zones of the prostate, the peripheral zones of the
      prostate, seminal vesicles, rectum wall, bladder, muscle and fat) were
      determined. The signal intensities of these structures were measured on
      reformatted axial images and compared against several structures of the pelvis.
      Correlation with various sequences and parameters was based on the signal-to
      noise ratio (SNR), the contrast ratio (CR) and the presence of artifacts.
      Student's t-test was used for statistical analysis. With Cube (TE/TR = 50 ms/2000
      ms), the average value of visual evaluation with artifacts was high, and SNR and
      CR were higher than for other sequence and parameters. Optimized MRI sequences
      and parameters were Cube (TE/TR = 50 ms/2000 ms) which provides improved SNR and
      CR and the presence of artifacts with operative assisted images for radical
      prostatectomy. These operative assisted images obtained from Cube (TE/TR = 50
      ms/2000 ms) are likely to be useful for surgery.

PMID- 23964535
TI  - [Measurement of non-invasive X-ray measuring instruments].

PMID- 23964534
TI  - [Application of N-isopropyl-p-[123I] iodoamphetamine quantification of regional
      cerebral blood flow using iterative reconstruction methods: selection of the
      optimal reconstruction method and optimization of the cutoff frequency of the
      preprocessing filter].
AB  - In cerebral blood flow tests using N-Isopropyl-p-[123I] Iodoamphetamine "I-IMP,
      quantitative results of greater accuracy than possible using the autoradiography
      (ARG) method can be obtained with attenuation and scatter correction and image
      reconstruction by filtered back projection (FBP). However, the cutoff frequency
      of the preprocessing Butterworth filter affects the quantitative value; hence, we
      sought an optimal cutoff frequency, derived from the correlation between the FBP
      method and Xenon-enhanced computed tomography (XeCT)/cerebral blood flow (CBF).
      In this study, we reconstructed images using ordered subsets expectation
      maximization (OSEM), a method of successive approximation which has recently come
      into wide use, and also three-dimensional (3D)-OSEM, a method by which the
      resolution can be corrected with the addition of collimator broad correction, to
      examine the effects on the regional cerebral blood flow (rCBF) quantitative value
      of changing the cutoff frequency, and to determine whether successive
      approximation is applicable to cerebral blood flow quantification. Our results
      showed that quantification of greater accuracy was obtained with reconstruction
      employing the 3D-OSEM method and using a cutoff frequency set near 0.75-0.85
      cycles/cm, which is higher than the frequency used in image reconstruction by the
      ordinary FBP method.

PMID- 23964536
TI  - [Youth health, school health].

PMID- 23964537
TI  - [Multidisciplinary consultation meetings: decision-making in palliative
      chemotherapy].
AB  - INTRODUCTION: Multidisciplinary consultation meetings provide an opportunity for
      specialists from different disciplines to engage in formal discussions over
      diagnostic and therapeutic strategies in oncology. In complex clinical
      situations, specialists discuss medical decisions collectively, particularly in
      cases involving palliative chemotherapy. The purpose of this study was to
      identify the factors considered in multidisciplinary consultation meetings in
      deciding whether palliative chemotherapy is needed. METHODS: A study was
      conducted over a three-month period in an adult hematology department in order to
      identify the criteria used in weekly multidisciplinary consultation meetings to
      determine whether palliative chemotherapy is required. The study only included
      patients who were confirmed to be in the palliative phase by all the doctors
      present at the multidisciplinary consultation meetings. The criteria cover 5
      areas related to patient's characteristics, patients'environment, the disease,
      scientific data and the objectives of palliative chemotherapy. RESULTS: The
      criteria considered in 100% of cases were related to the disease, the expected
      benefits of chemotherapy with palliative intent and patients' characteristics.
      The least important criteria were related to the patients' environment.
      Scientific data were not discussed during the multidisciplinary consultation
      meetings. CONCLUSION: The results show that the criteria used to determine
      whether chemotherapy with palliative intent is required are essentially of a
      medical nature. However, in palliative situations, factors related to patients'
      environment must be taken into account. In order to meet this requirement, it may
      be necessary to increase the participation of paramedical professionals and
      palliative care teams in multidisciplinary consultation meetings and to promote
      dialogue and collaboration with doctors and coordinating nurses.

PMID- 23964538
TI  - [An exploratory synthesis of knowledge brokering in public health].
AB  - There is a call for public health policies and interventions to be evidence
      based. Also, using knowledge brokers to foster the use of research results is
      increasingly recommended. This article presents an exploratory synthesis of the
      current state of knowledge on this new strategy We conducted a scoping study by
      consulting the main databases. Nineteen articles were included in the analysis,
      which was designed with a grid developed iteratively. The synthesis shows that
      knowledge brokering initiatives include i) planning activities (stakeholder
      identification, creation of networks and partnerships, context analysis, problem
      identification, needs identification), ii) support to the brokers (training,
      technical support, development of a practice guide), and iii) the brokerage
      activities themselves (information management, liaison between knowledge
      producers and users, training of users). Only four articles presented empirical
      data on the effects of brokers' activities. Three were associated with increased
      knowledge in the target audience. No study showed any impact on clinical
      behaviours or on public policy content. This synthesis highlights the challenges
      involved in knowledge brokering activities, as well as the characteristics and
      skills a broker should possess. While knowledge brokering appears promising,
      efforts must now be made to evaluate it more systematically to demonstrate its
      effectiveness.

PMID- 23964539
TI  - [Assessing the implementation of the 2010-2014 National Plan against HIV in the
      Regional Coordination Centers for the Fight against HIV (COREVIHs)].
AB  - INTRODUCTION: In France, 50,000 people are unaware of their HIV status because
      they have not been screened. Every year, there are nearly 7,000 new
      HIVinfections. To address this issue, the French Ministry of Health and Sport
      published the 2010-2014 National Plan against HIV/AIDS and other sexually
      transmitted diseases. A national survey was conducted among the Regional
      Coordination Centers for the Fight against HIV (COREVIHs) to assess their views
      of the National Plan and their current funding levels. METHOD: A questionnaire
      was sent to the presidents and coordinators of the 28 COREVIHs. RESULTS: After
      two reminders, 19 of the 28 COREVIHs responded. The National Plan was the
      original impetus for an assessmentofcurrent practices, accompanied by the
      implementation ofnew measures and new working groups. There is evidence that the
      COREVIHs are committed to developing incentive measures to promote screening and
      that they are also working to coordinate regional training programs in the area
      of screening and testing. The assessment also found that 11 COREVIHs were
      considering a reorganization of the CDAG/CIDDIST centers (CDAG: Free Anonymous
      Testing Center/ CIDDIST: STI Information, Testing and Diagnosis Center). Some
      COREVIHs have been involved in coordinating therapeutic education at a regional
      level. Most COREVIHs are also actively involved in the fight against
      discrimination. However, a number of obstacles to the implementation of the plan
      were identified. DISCUSSION: The purpose of this study was to examine the
      involvement of the COREVIHs in the implementation of the 2010-2014 National Plan
      against HIV The results indicate that implementing a system involving a specific
      form ofregionalcoordination of a public health problem is possible and should
      provide a basis for the decentralized implementation of public health plans.

PMID- 23964540
TI  - [Performing autopsies of all sudden deaths: a public health prevention strategy].
AB  - INTRODUCTION: In France, the management of sudden death (including nion-forensic
      autopsies) among adults could be improved. Thee number of sudden deaths may
      require a change in practice to promote screening for hereditary diseases. The
      purpose of this study was to identify areas for improvement and to assess the
      prevalence of non-forensic autopsies. METHODS: A retrospective study (2005-2010)
      conducted at Lille University Hospital resulted in the selection of 174 non
      forensic autopsies of adults who died suddenly. The criteria used were: the
      geographical origin of the bodies, indication, age, gender and the diagnosis
      ofdeath. RESULTS: The study found that the annual number of non-forensic
      autopsies was very low, with proportions ranging from 1.06 to 1.73 per 1,000
      deaths in the case of hospital deaths and from 0 to 0.43 per 1,000 deaths in the
      case of non-hospital deaths. Only 11 non-forensic autopsies of people who died at
      home were recorded over the study period, including 4 heart disease-related
      deaths. Overall, the results indicate that sudden death autopsies are poorly
      managed. DISCUSSION: Non-forensic autopsies are in decline, particularly in the
      case of deaths outside hospital, despite the fact that they are a crucial
      consideration for screening among relatives of a person who died sud!denly. The
      findings suggest that there needs to be an improvement in practice, a fact made
      possible by recent legislative developlments in France. A number of initiatives
      have been successful arId give hope that, like the reference centers specializing
      in unexpected infant deaths, reference centers specializing in sudden de'aths,
      which allow for more systematic non-forensic autopsies ofadults who die suddenly,
      might be created.

PMID- 23964541
TI  - [A qualitative assessment of the impact of a specialist nurse in outpatient
      urology consultations].
AB  - AIM: This paper presents the results of a prospective study of outpatient urology
      consultations designed to provide evidence of the benefits of using a specialist
      nurse to improve quality of care. METHODS: 135 patients (95 men and 40 women)
      were included in the study. Urinary disorders were defined using the
      International Classification of Functioning, Disability and Health (ICF),
      developed by the World Health Organization (WHO). The activity/ participation
      component was studied from a communication perspective before and after the
      urology consultation. Scores were obtained using a visual analogue scale (VAS).
      The VAS was also used to assess the role of the nurse as a facilitator
      (environmental factors component). A statistical analysis was performed on the
      population, as was an analysis of variance (ANOVA) of the activity/participation
      component. RESULTS: The participants were aged between 4years 10 months and
      96years (m = 63.29; standard deviation (SD) = 19.71). The median score for the
      urological disorders was 2. An analysis of variance of the two questions relating
      to the activity/participation component indicated a significant difference
      between the two groups (F = 6.4172; p < 0.001). A third question was used to
      assess the environmental factors component (nurse as facilitator), with a mean
      VAS score of97.79% (SD= 4.67). CONCLUSION: The purpose of this prospective study
      was to conduct a qualitative assessment of the impact of involving a specialist
      nurse in outpatient urology consultations. The study demonstrated that the
      qualitative impact of using a specialist nurse as a facilitator (environmental
      factors component) is extremely important for the participatory dimension of
      communication, particularly in terms of understanding medical information.

PMID- 23964543
TI  - [Development of decision support guidance of people in loss of autonomy in the
      care system in the Canton of Geneva's healthcare system].
AB  - AIM: The objective of this study is to use Iso-SMAF functional autonomy profiles
      (SMAF: French acronym for Functional autonomy measurement system) and other
      clinical and sociodemographic characteristics to develop algorithms that would
      support decision-making in orienting disabled people that would be adapted to
      current and future options available to a healthcare system in the Canton of
      Geneva. METHODS: A modified Delphi expert consultation, including the RAND/UCLA
      method, was used. After two rounds of consultations in which the experts
      responded to Web-based questionnaires, a nominal group completed the study.
      RESULTS: A total of 108 experts took part in the online consultation during the
      two rounds of consultation; 13 took part in the nominal group. In addition to
      belonging to various disciplines, the participants came from the different care
      structures within the Canton of Geneva. The findings made it possible to develop
      14 decision-making algorithms, eight of which received consensus support in the
      first round of consultation. The second round and nominal group achieved
      consensus for others. The profiles with moderate to severe cognitive impairment
      were those for which the orientation options required several rounds of voting.
      CONCLUSION: Since the orientation choices suggested by the algorithms were
      relatively standardized, they constitute recommendations that can guide
      professionals in orienting people.

PMID- 23964542
TI  - [The organizational benefits of the Kaizen approach at the Centre Hospitalier
      Universitaire de Sherbrooke (CHUS)].
AB  - AIM: The purpose of this study was to calculate the cost savings associated with
      using the kaizen approach in our hospital. METHODS: Originally developed in
      Japan, the kaizen approach, based on the idea of continuous improvement, has
      considerable support in North America, including in the Quebec health care
      system. This study assessed the first fifteen kaizen projects at the CHUS.
      RESULTS: Based on an economic evaluation, we showed that using the kaizen
      approach can result in substantial cost savings. CONCLUSION: The success of the
      kaizen approach requires compliance with specific prerequisites. The future of
      the approach will depend on our ability to comply with these prerequisites. More
      specifically, such compliance will determine whether the approach is merely a
      passing fad or a strategy for improving our management style to promote greater
      efficiency.

PMID- 23964544
TI  - [Information and active patient participation using an interactive booklet in the
      prescription of antihypertensive drugs in primary care].
AB  - AIM: Antihypertensive drugs are thought to be responsible for adverse drug events
      in 25% of patients, with severe consequences in 13% of cases. The purpose of this
      study was to develop an interactive booklet designed to inform and involve
      patients with a view to preventing adverse drug events. METHODS: The development
      of the booklet involved several stages, including a literature review, a Delphi
      survey, a readability assessment, a qualitative study in primary care, a revision
      process, and graphic design work. 27 experts (patients, general practitioners,
      public health practitioners, cardiologists, geriatricians, psychologists,
      economists, pharmacists, nurses and ethicists) participated in the Delphi survey,
      while the qualitative study was based on a sample that included 7 doctors, 13
      patients and 2 healthcare assistants. RESULTS: We developed an interactive
      booklet containing information items on the benefits and risks of
      antihypertensive drugs, a care plan to be completed by the patient, and a form
      for reporting adverse drug events. Ambiguous sentences and incomprehensible
      medical terms were rephrased. The time required to present the booklet and ease
      of use were key acceptability criteria for caregivers. Among the patients, the
      study found that interest in the booklet required clear evidence of an expected
      benefit. CONCLUSION: An understandable and acceptable interactive booklet was
      developed using a systematic process to prevent severe adverse drug events in
      primary care.

PMID- 23964545
TI  - [Using telemedicine to improve chronic disease monitoring].
AB  - AIM: The purpose of this study was to understand how home telecare technologies
      can be used to improve services for people with chronic diseases. METHODS:
      Canadian elders with at least one of the targeted chronic diseases (COPD, heart
      failure, hypertension, diabetes) were asked to use telehomecare equipment. The
      data needed to assess the implementation process and to monitor outcomes were
      collected through participatory observation, documentary analysis and interviews.
      RESULTS: The study found that the technology has a number of benefits for
      patients, particularly in terms of access to health services. By enabling
      patients to access more information about their health, the use of the
      technology, combined with an educational program, contributes to increasing their
      capacity for self-management. The results also indicate that the telehomecare
      equipment had a positive impact on clinical decision-making. By facilitating
      health professionals' access to information and expertise, it was found to
      promote interprofessional practice. The study found that telehomecare technology
      has an organizational impact on practice and requires organizational adaptation,
      the form of which will depend on local organizational and clinical settings.
      CONCLUSION: The results suggest that telehomecare technology helps to create
      conditions that need to be met by health care organizations in order to improve
      service delivery to people with chronic diseases, particularly with regard to
      interprofessional collaboration, health professionals' access to information and
      expertise and active patient participation. However, the successful
      implementation of the technology requires a detailed analysis of the settings in
      which it is used.

PMID- 23964546
TI  - [A study of the prevalence of infectious markers in blood donors in rural areas.
      The case of Kamina hospital].
AB  - INTRODUCTION: The transmission of infectious agents such as the human
      immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV) and syphilis
      is the greatest threat to transfusion recipient safety. The purpose of this study
      was to determine the seroprevalence of infectious markers with a view to
      contributing to transfusion safety by selecting donors. METHODS: A retrospective
      analysis of the medical records ofblood donors covering the period 1 January to
      31 December 2008 was conducted. The global seroprevalence of HIV HBV HCV and
      syphilis was, respectively, 2.9%, 1.6%, 0.2% and 0.2%. A high seroprevalence was
      found in the 16-25 and 46-55-year age groups, while there was a high prevalence
      of syphilis in the 16-25-year age group. RESULTS: The results confirm the
      presence of infection by hepatitis B in Kamina and provide an initial insight
      into the circulation of the hepatitis C virus, the HIV virus and syphilis in the
      blood donor population. DISCUSSION: Rigorous selection and screening procedures
      among blood donors are needed to ensure transfusion recipient safety.

PMID- 23964547
TI  - [Knowledge and practices of health care workers in the area of healthcare
      associated infection risks. A case study in a district hospital in Burkina Faso].
AB  - INTRODUCTION: Healthcare-associated infections are a common consequence of unsafe
      health care practices and are a major issue for patient safety. Health care
      workers play a key role in patient safety and the quality of care, with factors
      such as poor compliance with hygiene standards and poor knowledge of infection
      risks having a major impact. However, the role of health care workers in patient
      safety has been overlooked in the literature. The objectives of this study were
      i) to examine health care workers' awareness of infection risks and ii) to assess
      levels of hand hygiene compliance and barriers to patient safety. METHODS: A one
      day cross-sectional survey was conducted in June 2011 at the Ziniare health
      district hospital. The study focused on the health care workers present on the
      day of the survey in hospital care units and involved interviews and
      observations. RESULTS: The study found that 30.04% of the health care workers
      knew the definition of healthcare-associated infections. Only 44.4% of the health
      care workers reported that the hands of health care workers (in the event of poor
      hand hygiene compliance) were the main mode of transmission of germs between
      patients in a care facility. In addition, only 21.43% (12/56) of the participants
      were aware of the main factors that increase the risk of health care-associated
      infections. The level of compliance with hygiene protocols was low (36.85%).
      CONCLUSION: The promotion of patient safety and quality of care requires a focus
      on training and behavior change among health care workers.

PMID- 23964548
TI  - [Hepatitis B knowledge among secondary school students in Cote d'Ivoire].
AB  - AIM: The purpose of this study was to assess hepatitis B knowledge among
      secondary school students' in Cote d'Ivoire in order to promote the inclusion of
      hepatitis B education in school curricula. MATERIAL AND METHODS: a single cross
      sectional survey involving six schools (7,376 students) was conducted. Data were
      collected using a self-administered questionnaire. RESULTS: All students present
      on the day of the survey agreed to participate in the study (100%, n = 3,352).
      The mean age of the participants was 17.9 years (10-26 years), with a male-to
      female sex ratio of 1.68. Among them, 2,552 (76.6%) had heard of the HVB. School
      was the main source of information (12%), after the mass media (62%). The
      causative agent of the disease was known by 74.1% of students (n = 2,484), sexual
      transmission by 39.3% (n = 1316), and blood-borne transmission by 57.2% (n =
      1919). Respectively 29%, 40% and 41% of the students were aware that acupuncture,
      body piercing and tattooing are high-risk practices. Only 35.7% of the students
      knew that there was an effective vaccine. The factors associated with hepatitis B
      knowledge were: being aged 16 to 20 years (OR = 1.73 [95% CI 1.198 to 2.49]),
      living in a permanent house or apartment (OR = 1.58 [95% CI 1.234 to 2.02]) or in
      a house or apartment with no more than 2 persons per room (OR = 1.41 [95% CI 1.15
      to 1.74]), being in terminale (final year of high school) (OR = 2.54 [2.01 to 3,
      20IC95%]), and having two working parents (OR =1.54 [95% CI 1.25 to 1.88]).
      CONCLUSION: The students' knowledge of the hepatitis B virus was found to be
      inadequate and superficial. Early awareness programs provided as part of the
      official curriculum and measures to improve the social conditions of students
      should help to improve knowledge in this area.

PMID- 23964549
TI  - [Self-medication among patients admitted to the emergency department of Kinshasa
      University Hospital].
AB  - A cross-sectional descriptive study was conducted at Kinshasa University Hospital
      (KUH) to determine the prevalence of self-medication among patients admitted to
      KUH and to identify commonly used drugs. 391 patients aged 14 to 92 years
      admitted to the KUH emergency department between 15 January and 15 February 2011
      were included in the study. 233 patients out of a total of 391 (59.6%) used self
      medication between the onset of symptoms and the visit to KUH. The number of
      drugs used ranged from 1 to 7. Of the 233 patients who practiced self-medication,
      224 (96.1%) used pharmaceutical drugs alone, 4 (1.7%) used traditional African
      remedies alone, 1 (0.4%) used Chinese medicine alone, and 4 (1.7%) combined
      pharmaceutical drugs with traditional African remedies. Analgesics and
      antipyretics (44.3%), non-steroidal anti-inflammatory drugs (NSAIDs) (26.3%),
      antimalarials (20.6%) and antibacterials (12.3%) were the most commonly used
      pharmaceutical drugs. Paracetamol was the most commonly used analgesic and
      antipyretic (89.1%). Among NSAIDs, diclofenac (65%) was the most widely used.
      Artemisinin-based combination drugs (40.4%) were the most commonly used
      antimalarials, with lumefantrine being the most common. The most widely reported
      antibacterials were betalactam antibiotics (ampicillin and amoxicillin) (42.9%).
      The results show that self-medication, based mainly on commonly prescribed
      pharmaceutical drugs, appears to be a common therapeutic option before seeking
      hospital care and may be a major threat to individual and community health.

PMID- 23964550
TI  - In vitro methods for diagnosing nonimmediate hypersensitivity reactions to drugs.
AB  - Nonimmediate drug hypersensitivity reactions (DHRs) are difficult to manage in
      daily clinical practice, mainly owing to their heterogeneous clinical
      manifestations and the lack of selective biological markers. In vitro methods are
      necessaryto establish a diagnosis, especially given the low sensitivity of skin
      tests and the inherent risks of drug provocation testing. In vitro evaluation of
      nonimmediate DHRs must include approaches that can be applied during the
      different phases of the reaction. During the acute phase, monitoring markers in
      both skin and peripheral blood helps to discriminate between immediate and
      nonimmediate DHRs with cutaneous responses and to distinguish between reactions
      that, although they present similar clinical symptoms, are produced by different
      immunological mechanisms and therefore have a different treatment and prognosis.
      During the resolution phase, in vitro testing is used to detect the response of T
      cells to drug stimulation; however, this approach has certain limitations, such
      as the lack of validated studies assessing sensitivity. Moreover, in vitro tests
      indicate an immune response that is not always related to a DHR. In this review,
      members of the Immunology and Drug Allergy Committee of the Spanish Society of
      Allergy and Clinical Immunology (SEAIC) provide an overview of the most widely
      used in vitro tests for evaluating nonimmediate DHRs.

PMID- 23964551
TI  - Evaluation of fungal extracts to determine immunomodulatory properties.
AB  - BACKGROUND: Immunoglobulin E-mediated allergies have doubled in prevalence during
      recent decades in developed countries.This increase has been attributed, in part,
      to high hygiene standards, which have reduced exposure to microbes. The capacity
      of microbes to induce type 1 helper T cell (TH1) responses may imply suppression
      of TH2 responses. However, little research has been performed with fungal
      extracts. OBJECTIVES: To evaluate the TH1-inducing properties of fungal extracts.
      METHODS: A total of 24 fungal extracts, including Cetavlon-precipitated
      polysaccharides from different yeasts, molds, and mushrooms were prepared.The
      extracts were screened for production of interferon (IFN)gamma in human
      peripheral blood mononuclear cells. The active compounds were further purified by
      mild acid hydrolysis and by column chromatography and studied in human peripheral
      blood mononuclear cells. RESULTS: Expression of IFN-gamma was induced by several
      extracts. The strongest expression of IFN-gamma was induced by Candida albicans.
      The Cetavlon-precipitated mannans of fungi induced cytokine responses that were
      similar or superior to those induced by whole extracts, C albicans being the most
      potent inducer of IFN-gamma. Column chromatography-fractionated mild acid
      hydrolysis of Calbicans mannan was performed. Fractions containing
      oligosaccharides of 12-16 mannoses induced production of tumor necrosis factor.
      CONCLUSIONS: Several fungal extracts induce IFN-gamma. The most promising
      preparations were yeast-derived oligosaccharides. Further research should be
      focused on purification and eventual synthesis of the extracts.

PMID- 23964552
TI  - Costs associated with workdays lost and utilization of health care resources
      because of asthma in daily clinical practice in Spain.
AB  - BACKGROUND: Asthma is associated with high indirect costs due to lower work
      productivity and higher absenteeism and presenteeism. OBJECTIVES: To study loss
      of productivity measured using the lost workday equivalent (LWDE) index and
      health care utilization in asthmatics depending on age, geographical location,
      time period, severity, and level of asthma control. PATIENTS AND METHODS: In this
      cross-sectional, observational, epidemiological multicenter study, 120 allergists
      nationwide were asked to select asthmatic patients aged 18 to 65 years who were
      evenly distributed according to the 4 levels of asthma severity (Global
      Initiative on Asthma) during 3 different seasons. The participants collected
      sociodemographic data, spirometry values, Asthma Control Test (ACT) score, health
      care utilization data, perceived stress according to the Impact on Work
      Productivity Index (IMPALA, indice del Impacto de la Enfermedad en la
      Productividad Laboral), and score on the Sheehan disability scale. The LWDE index
      was used to measure the number of workdays lost and the number of workdays with
      asthma symptoms combined with the percentage for average performance at work.
      RESULTS: The study sample comprised 1098 patients (58.7% females; 48.5% aged 18
      40 and 51.5% aged 41-65). According to the ACT score, disease was uncontrolled in
      57.6% of patients, well controlled in 32.8%, and totally controlled in 9.6%. The
      mean cost due to workdays lost was Euro 285.81/patient/mo (95% CI, Euro 252.71
      318.92). Indirect costs were significantly higher in older patients (41-65 years,
      Euro 405.08; 95% CI, 348.97-461.19), patients with more severe disease (Euro
      698.95; 95% CI, 588.63-809.27), and patients with more poorly controlled asthma
      (Euro 466.86; 95% CI, Euro 414.39-519.33). The average cost of health care units
      per patient for each 3-month period was Euro1317.30 (95% CI, Euro 1151.34-Euro
      1483.26). Indirect costs were significantly higher in older patients (Euro
      2104.00 in patients aged 18-40 vs Euro 3301.55 in patients aged 41-65), in
      northern and central regions, in severe disease (Euro 2921.63), and in more
      poorly controlled asthma (Euro 1799.42). CONCLUSION: Our findings could prove
      useful for physicians and health care providers.

PMID- 23964553
TI  - Relationship between polymorphisms in IL4 and asthma in Japanese women: the
      Kyushu Okinawa Maternal and Child Health Study.
AB  - BACKGROUND: Interleukin (IL) 4 plays a critical role in immune responses by
      acting as a growth factor for type 2 helper T cells and inducing immunoglobulin
      (Ig) class switching to IgE. Epidemiological evidence of the relationship between
      single-nucleotide polymorphisms (SNPs) in IL4 and asthma is inconsistent.
      OBJECTIVES: We examined the association between the IL4 SNPs rs2243250,
      rs2070874, rs2227284, and rs2243290 and asthma in young adult Japanese women.
      METHODS: The study population comprised 89 women who met the criteria of the
      European Community Respiratory Health Survey (ECRHS) for asthma. The control
      group comprised 1281 nonasthmatic women (ECRHS criteria) who had not been
      diagnosed with asthma by a physician. Adjustment was made for age, region of
      residence, presence of older siblings, smoking, and education. RESULTS: Compared
      with the AA genotype of rs2243290, the AC genotype, but not the CC genotype, was
      significantly associated with a reduced risk of asthma: the adjusted odds ratio
      for the AC genotype was 0.62 (95% CI, 0.39-0.996). No evident relationships were
      found between rs2243250, rs2070874, or rs2227284 and asthma. None of the
      haplotypes were significantly associated with asthma. No significant interactions
      were found between the 4 SNPs under study and smoking with respect to the risk of
      asthma. CONCLUSIONS: Ours is the first study in a non-Western population to show
      that the IL4 SNP rs2243290 was significantly associated with the risk of asthma.
      Smoking did not significantly modify the gene-disease associations under study.

PMID- 23964554
TI  - Peripheral blood eosinophil counts predict the prognosis of drug eruptions.
AB  - BACKGROUND: Previous studies indicated that eosinophils infiltrate the skin
      during drug eruptions and that counts may become elevated in circulation.
      However, little is known about the role of eosinophils in the prognosis of
      patients with drug eruption. OBJECTIVE: This study aims to investigate the
      correlation between circulating eosinophil counts and the prognosis of patients
      with drug eruption. METHODS: A total of 113 patients were enrolled in this study.
      Clinical features, peripheral blood eosinophil counts, and liver function were
      analyzed in patients and controls. RESULTS: Our study indicated that eosinophils
      changed dynamically in different types of drug eruption and that mean eosinophil
      counts in patients with erythema multiforme-type drug eruption were significantly
      higher than in patients with other types of eruption. Most patients with
      eosinophilia had poor liver function, prolonged corticosteroid use, and extended
      hospitalization, all of which indicate severe disease. CONCLUSIONS: Our data
      suggest that circulating eosinophil counts were positively correlated with the
      severity of the drug eruption. Therefore, corticosteroids may be needed to treat
      patients with eosinophilia in clinical practice.

PMID- 23964555
TI  - A polymorphism in ORMDL3 is associated not only with asthma without rhinitis but
      also with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Asthma is a heterogeneous disease, and asthmatic patients without
      rhinitis more commonly have fixed airway obstruction, a feature that is also
      typical of chronic obstructive pulmonary disease (COPD). The Dutch hypothesis
      suggests that both COPD and asthma have common genetic risk factors. The purpose
      of this study was to assess the association between the polymorphism rs4795405 in
      the known asthma candidate gene ORMDL3 and asthma with and without rhinitis. We
      also analyzed COPD in order to investigate whether, in addition to a clinical
      overlap, there might also be a genetic overlap between COPD and asthma. METHODS:
      The population of this genetic association study comprised 493 Slovenian adults,
      distributed as follows: 131 patients with asthma (59 had asthma with rhinitis and
      72 asthma without rhinitis), 59 patients with rhinitis only, 133 patients with
      COPD, and 170 controls. Genotypes for rs4795405 were determined using the TaqMan
      genotyping assay. RESULTS: rs4795405 was specifically associated with asthma
      without rhinitis. Assuming a recessive genetic model, we found the CC genotype in
      26% of healthy controls, in 24% of patients with asthma with rhinitis (P = .862),
      and in 44% of patients with asthma without rhinitis (P = .006). Polymorphism
      rs4795405 was also associated with COPD, for which the CC genotype was found in
      37% of cases (P = .045). CONCLUSIONS: rs4795405 was strongly associated with
      asthma without rhinitis, a subtype of asthma for which a higher degree of airway
      obstruction was found. These results show the importance of analyzing different
      asthma phenotypes in genetic association studies. We also observed a genetic
      overlap between COPD and asthma without rhinitis.

PMID- 23964556
TI  - Association between genetic polymorphisms of beta2 adrenergic receptors and
      nocturnal asthma in Egyptian children.
AB  - BACKGROUND: Identification of the genetic basis of asthma may contribute to the
      discovery of effective asthma drugs. OBJECTIVE: Our aim was to estimate the
      association between B2 adrenergic receptor (ADRB2) polymorphisms and nocturnal
      asthma in Egyptian children. METHODS: ADRB2 polymorphisms Gly16 and Glu27 were
      genotyped in 200 Egyptian children (90 with nocturnal asthma and 110 healthy
      controls) using allele-specific polymerase chain reaction. RESULTS: The
      homozygous (Gly16) genotype significantly increased the risk of nocturnal asthma
      (odds ratio [OR], 3.2; 95% CI, 1.3-7.7; P = .003), as did the Gly allele (OR,
      1.8: 95% CI, 1.2-2.8). CONCLUSIONS: Our study demonstrated that nocturnal asthma
      was associated with ADRB2 Arg/Gly polymorphisms but not with ADRB2 Gln/Glu
      polymorphisms.

PMID- 23964557
TI  - Nonallergic airway hyperresponsiveness and allergen-specific IgE levels are the
      main determinants of the early and late asthmatic response to allergen.
AB  - BACKGROUND: Conflicting results have been reported in studies of predictive
      factors for airway responsiveness to allergens during bronchial challenges.
      OBJECTIVE: The aim of this study was to assess determinants of airway
      responsiveness to 3 different allergens during standardized bronchial challenges.
      METHODS: Data were collected from asthmatic patients who participated in allergen
      challenge trials between 2000 and 2006 (cat, n = 37; house dust mite [HDM], n =
      35; grass pollen, n = 27). PD20 (provocative dose causing a 20% fall in forced
      expiratory volume in the first second) methacholine, PD20 allergen, allergen skin
      test endpoint, allergen-specific immunoglobulin (Ig) E levels, and late asthmatic
      response were analyzed for each allergen group. RESULTS: During the early
      asthmatic response, a significant relationship was found between PD20 allergen
      and PD20 methacholine (P < .01 for cat, HDM, and grass pollen), as well as
      between PD20 allergen and allergen-specific IgE levels (P < .05 for cat and HDM).
      No relationship was observed between PD20 allergen and allergen skin test
      endpoint (P > .05). Late asthmatic response was significantly more frequent after
      HDM challenge than after cat or grass pollen challenges (57.1% vs16.2% and 33.3%,
      P < .01). Dual responders during HDM challenges had significantly higher allergen
      specific IgE levels (P < .05) and higher nonallergic airway responsiveness (P <
      .05). CONCLUSION: Nonallergic airway hyperresponsiveness and allergen-specific
      IgE levels were the main determinants of early and late asthmatic responses. HDM
      challenges were the most interesting model with regard to the occurrence of late
      asthmatic response. In contrast to previous publications and to the official
      statement on standardized challenge testing with sensitizing stimuli, skin
      sensitivity appears to be a poor predictor of the early asthmatic response.

PMID- 23964558
TI  - Tolerability to etoricoxib in patients with aspirin-exacerbated respiratory
      disease.
AB  - BACKGROUND: The use of selective cyclooxygenase (COX) 2 inhibitors as an
      alternative to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs)
      has been suggested for patients with aspirin-exacerbated respiratory disease
      (AERD). OBJECTIVE: To evaluate tolerability to etoricoxib, a second-generation
      COX-2 inhibitor with high in vitro selectivity for COX-2 in patients with AERD.
      METHODS: We conducted a retrospective review of patients with suspected aspirin
      intolerance seen between October 2007 and April 2012. Single-blind, placebo
      controlled oral challenges with increasing doses of aspirin and etoricoxib were
      performed on 3 different days. RESULTS: Of 262 patients with suspected aspirin
      intolerance, 248 underwent challenge testing with aspirin and 122 (49.2%) showed
      positive test results. In 104 of these aspirin-sensitive patients, etoricoxib was
      tested as an alternative drug and was tolerated in all but 3 (2.9%), who
      developed a positive asthmatic reaction. CONCLUSIONS: The highly selective COX-2
      inhibitor etoricoxib was tolerated in most but not all patients tested. An oral
      provocation test is therefore recommended before prescribing etoricoxib for
      patients with AERD.

PMID- 23964559
TI  - Fixed drug eruption due to dextromethorphan with tolerance to other opioids.

PMID- 23964560
TI  - Rifamycin-associated postoperative allergic contact dermatitis in a 70-year-old
      patient.

PMID- 23964561
TI  - Changes in the asthma control test score in patients with work-related asthma.

PMID- 23964562
TI  - Occupational contact dermatitis to methacrylates in an orthopaedic operating room
      nurse.

PMID- 23964563
TI  - Occupational wheat contact dermatitis and treatment with omalizumab.

PMID- 23964564
TI  - Naturally occurring sulfonium-ion glucosidase inhibitors and their derivatives: a
      promising class of potential antidiabetic agents.
AB  - In humans, four different enzymes mediate the digestion of ingested
      carbohydrates. First salivary and pancreatic alpha-amylases, the two endoacting
      retaining glucosidases, break down the complex starch molecules into smaller
      linear maltose-oligomers (LM) and branched alpha-limit dextrins (alphaLDx). Then
      two retaining exoglucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase
      (SI), convert those molecules into glucose in the small intestine. The small
      intestinal brush-border epithelial cells anchor MGAM and SI, and each contains a
      catalytic N- and C-terminal subunit, ntMGAM, ctMGAM, ntSI, and ctSI,
      respectively. All four catalytic domains have, to varying extents, alpha-1,4
      exohydrolytic glucosidase activity and belong to the glycoside hydrolase family
      31 (GH31). ntSI and ctSI show additional activity toward alpha-1,6 (isomaltose
      substrates) and alpha-1,2 (sucrose) glycosidic linkages, respectively. Because
      they mediate the final steps of starch digestion, both MGAM and SI are important
      target enzymes for the treatment of type-2 diabetes. Because of their potent
      inhibitory activities against the mammalian intestinal alpha-glucosidases,
      sulfonium-ion glucosidase inhibitors isolated from the antidiabetic herbal
      extracts of various Salacia species have received considerable attention
      recently. Thus far, researchers have isolated eight sulfonium-ion glucosidase
      inhibitors from Salacia species: salaprinol, salacinol, ponkoranol, kotalanol,
      and four of their corresponding de-O-sulfonated compounds, the structures of
      which comprise a 1,4-anhydro-4-thio-d-arabinitol and a polyhydroxylated acyclic
      side chain. Some of these compounds more strongly inhibit human intestinal alpha
      glucosidases than the currently available antidiabetic drugs, acarbose and
      miglitol, and could serve as lead candidates in the treatment of type-2 diabetes.
      In this Account, we summarize progress in the field since 2010 with this class of
      inhibitors, with particular focus on their selective inhibitory activities
      against the intestinal glucosidases. Through structure-activity relationship
      (SAR) studies, we have modified the natural compounds to derive more potent,
      nanomolar inhibitors of human MGAM and SI. This structural optimization also
      yielded the most potent inhibitors known to date for each subunit. Furthermore,
      we observed that some of our synthetic inhibitors selectively blocked the
      activity of some mucosal alpha-glucosidases. Those results led to our current
      working hypothesis that selective inhibitors can dampen the action of a fast
      digesting subunit or subunits which places the burden of digestion on slower
      digesting subunits. That strategy can control the rate of starch digestion and
      glucose release to the body. Decreasing the initial glucose spike after a
      carbohydrate-rich meal and extending postprandial blood glucose delivery to the
      body can be desirable for diabetics and patients with other metabolic syndrome
      associated diseases. 

PMID- 23964566
TI  - Highly efficient visual detection of trace copper(II) and protein by the quantum
      photoelectric effect.
AB  - This work presented a photocurrent response mechanism of quantum dots (QDs) under
      illumination with the concept of a quantum photoelectric effect. Upon
      irradiation, the photoelectron could directly escape from QDs. By using nitro
      blue tetrazolium (NBT) to capture the photoelectron, a new visual system was
      proposed due to the formation of an insoluble reduction product, purple formazan,
      which could be used to visualize the quantum photoelectric effect. The
      interaction of copper(II) with QDs could form trapping sites to interfere with
      the quantum confinement and thus blocked the escape of photoelectron, leading to
      a "signal off" visual method for sensitive copper(II) detection. Meanwhile, by
      using QDs as a signal tag to label antibody, a "signal on" visual method was also
      proposed for immunoassay of corresponding protein. With meso-2,3
      dimercaptosuccinic-capped CdTe QDs and carcino-embryonic antigen as models, the
      proposed visual detection methods showed high sensitivity, low detection limit,
      and wide detectable concentration ranges. The visualization of quantum
      photoelectric effect could be simply extended for the detection of other targets.
      This work opens a new visual detection way and provides a highly efficient tool
      for bioanalysis. 

PMID- 23964567
TI  - Relationship between chemical structure and supramolecular effective molarity for
      formation of intramolecular H-bonds.
AB  - Effective molarity (EM) is a key parameter that determines the efficiency of a
      range of supramolecular phenomena from the folding of macromolecules to
      multivalent ligand binding. Coordination complexes formed between zinc porphyrins
      equipped H-bond donor sites and pyridine ligands equipped with H-bond acceptor
      sites have allowed systematic quantification of EM values for the formation of
      intramolecular H-bonds in 240 different systems. The results provide insights
      into the relationship of EM to supramolecular architecture, H-bond strength, and
      solvent. Previous studies on ligands equipped with phosphonate diester and ether
      H-bond acceptors were inconclusive, but the experiments described here on ligands
      equipped with phosphine oxide, amide, and ester H-bond acceptors resolve these
      ambiguities. Chemical double-mutant cycles were used to dissect the thermodynamic
      contributions of individual H-bond interactions to the overall stabilities of the
      complexes and hence determine the values of EM, which fall in the range 1-1000
      mM. Solvent has little effect on EM, and the values measured in toluene and
      1,1,2,2-tetrachloroethane are similar. For H-bond acceptors that have similar
      geometries but different H-bond strengths (amide and ester), the values of EM are
      very similar. For H-bond acceptors that have different geometries but similar H
      bond strengths (amide and phosphonate diester), there is little correlation
      between the values of EM. These results imply that supramolecular EMs are
      independent of solvent and intrinsic H-bond strength but depend on supramolecular
      architecture and geometric complementarity. 

PMID- 23964568
TI  - Cumulative disadvantage? Exploring relationships between neighbourhood
      deprivation trends (1991 to 2006) and mortality in New Zealand.
AB  - BACKGROUND: Area-level socioeconomic deprivation has been shown to exert an
      independent effect on both individual and population health outcomes and health
      related behaviours. Evidence also suggests that health and economic inequalities
      in many countries are increasing in some areas but may be on the decline in
      others. While area-level deprivation at a single point in time is known to
      influence health, the literature relating to longitudinal deprivation of
      communities and associated health impacts is sparse. This research makes a
      methodological contribution to this literature. METHODS: Using a Latent Class
      Growth Model, we identified 12 deprivation trends (1991-2006) for small areas (n
      = 1621) in New Zealand. We then fitted regression models to assess the effects of
      trends of relative deprivation on a) all-cause mortality, and b) cardiovascular
      mortality (2005-2007) by census area unit. For comparison, we also fitted
      regression models to assess the effect of deprivation deciles (in 2006) on
      outcomes a) and b). RESULTS: Using trends, we found a positive association
      between deprivation and mortality, except for two trends for both all-cause and
      CVD-related mortality. When comparing trends and deciles of deprivation, we
      observed similar patterns. However, we found that AIC values were slightly lower
      for the model including deciles, indicating better model fit. CONCLUSION: While
      we found that current deprivation was a slightly better predictor of mortality,
      the approach used here offers a potentially useful alternative. Future
      deprivation research must consider the possible loss of information about health
      benefits of living in areas where relative deprivation has improved in cross
      sectional analyses.

PMID- 23964565
TI  - Strategies on the nuclear-targeted delivery of genes.
AB  - To improve the nuclear-targeted delivery of non-viral vectors, extensive effort
      has been carried out on the development of smart vectors which could overcome
      multiple barriers. The nuclear envelope presents a major barrier to transgene
      delivery. Viruses are capable of crossing the nuclear envelope to efficiently
      deliver their genome into the nucleus through the specialized protein components.
      However, non-viral vectors are preferred over viral ones because of the safety
      concerns associated with the latter. Non-viral delivery systems have been
      designed to include various types of components to enable nuclear translocation
      at the periphery of the nucleus. This review summarizes the progress of research
      regarding nuclear transport mechanisms. "Smart" non-viral vectors that have been
      modified by peptides and other small molecules are able to facilitate the nuclear
      translocation and enhance the efficacy of gene expression. The resulting
      technology may also enhance delivery of other macromolecules to the nucleus.

PMID- 23964569
TI  - Development and validation of a sensitive, high-throughput bioassay for the
      adhesion of radiolabeled E. coli to uroepithelial cells in vitro.
AB  - Vaccinium macrocarpon (cranberry) products have been used to prevent
      uropathogenic Escherichia (E.) coli adherence to uroepithelial cells (UEC) and
      may help reduce risk of urinary tract infection. Reported herein are the
      development and validation of an assay to assess antiadhesion activity of V.
      macrocarpon extracts and human urine. P-fimbriated E. coli (CFT073) was labeled
      with 3H-uridine, then co-incubated with HTB-4 UEC at a 400:1 ratio. V.
      macrocarpon extracts (0-17 mg proanthocyanidins/mL) were added to 3H-labeled E.
      coli before co-incubating with UEC. The assay yielded a sensitive inhibition
      curve: the lower limit of detection and half-maximal inhibitory concentration
      were 0.43 and 1.59 mg proanthocyanidins/mL for V. macrocarpon extract CEP 55;
      intra- and interassay coefficients of variance were <10% and <15%, respectively.
      V. macrocarpon extract CEP 3283 showed identical adhesion inhibition. Serial
      dilutions of urine from human participants who consumed V. macrocarpon beverages
      showed a linear decrease in antiadhesion activity. Antiadhesion assays conducted
      with urine from a human intervention study also showed good agreement with
      results obtained using the hemagglutination assay. Therefore, a sensitive, high
      throughput, biologically relevant antiadhesion assay using 3H-E. coli co
      incubated with UEC is reported, which can be used for studying the action of V.
      macrocarpon bioactives.

PMID- 23964571
TI  - The attention demands of movements.
AB  - The probe technique has been employed extensively to measure the attention
      demands of movement control. Inherent in any RT paradigm is the potential
      confounding effect of anticipation. Experiment 1 studied this problem by varying
      probe frequency (or, conversely, catch-trial frequency) for three independent
      groups of subjects performing the same movement. Probe frequencies of one-third
      and two-thirds produced V-shaped curves of probe RT plotted against probe
      position within the movement, while a three-thirds condition was described by a
      negatively sloped linear function. Because of the different shaped curves it was
      recommended that a two-thirds frequency be adopted by all researchers in this
      area. Experiments 2 and 3 looked at the effects of movement length and movement
      time on the attention demands of movement. Shorter (11-cm) movements were more
      attention demanding in the middle of the movement than the longer (50-cm)
      movements, but movement time had no effect. 

PMID- 23964572
TI  - IRIS Pigmentation and Reactive Motor Performance.
AB  - Worthy's (1974) hypothesis that brown-eyed subjects respond faster than blue-eyed
      subjects on reactive motor tasks was tested. Experiment 1 compared dark-brown and
      blue-eyed subjects on rotary pursuit and choice response time tasks. There was a
      tendency for the predicted effect, but it was only evident for choice responding
      where speed was the principal performance criterion. In Experiment 2 iris
      pigmentation effects were found to be limited to the reaction-time component, but
      not the movement time component, of a simple motor response. Differences in the
      filtering of lightwaves and in CNS neuro-pigmentation are mechanisms commonly
      used to explain these findings. Iris pigmentation effects were found for both
      auditory and visual stimuli, thus supporting the neuro-pigmentation explanation. 

PMID- 23964570
TI  - Molecular and functional characterization of canine interferon-epsilon.
AB  - In this study, we provide the first comprehensive annotation of the entire family
      of canine interferons (IFNs). Canine IFN-epsilon (IFNE), IFN-kappa (IFNK), and
      IFN-lambda (IFNL) were discovered for the first time. Ten functional and 2
      truncated IFN-alpha (IFNA) pseudogenes were found in the genome, which also
      enriched the existing knowledge about canine IFNA. The canine type I IFN genes
      are clustered on chromosome 11, and their relative arrangements are illustrated.
      To further investigate the biological activity of canine IFNE, it was expressed
      and purified in Escherichia coli. Recombinant canine IFNE (rCaIFN-epsilon)
      displayed potent antiviral activity on both homologous and heterologous animal
      cells in vitro, indicating that rCaIFN-epsilon has more broad cross-species
      activity than recombinant canine IFNA (rCaIFN-alpha). The antiviral activities of
      rCaIFN-epsilon and rCaIFN-alpha7 against different viruses on MDCK cells were
      also evaluated. The antiviral activities of recombinant canine IFNK and IFNL were
      demonstrated using a VSV-MDCK virus-target cell system. rCaIFN-epsilon exhibited
      a significant anti-proliferative response against A72 canine tumor cells and MDCK
      canine epithelial cells in a dose-dependent manner. rCaIFN-alpha7 was
      approximately 16-fold more potent than rCaIFN-epsilon in promoting natural killer
      cell cytotoxicity activity. Further, rCaIFN-epsilon can activate the JAK-STAT
      signaling pathway.

PMID- 23964573
TI  - The effect of irrelevant information on the stages of processing.
AB  - The Sternberg (1969) additive factor method was used to determine whether the
      stimulus encoding stage was affected by an irrelevant auditory stimulus presented
      during a visual choice reaction time task. Subjects responded to an X or an O by
      pressing a left-or right-hand key. Onset of this visual stimulus was accompanied
      by a tone to the left, right, or both ears. Reactions were slower when the locus
      of the tone did not correspond with the side of the response than when it did
      correspond. Manipulation of the quality of the visual stimulus, assumed to affect
      the stimulus encoding stage, did not alter the effect of the irrelevant auditory
      cue. In a parallel experiment, the same stimuli were used, but the responses
      employed were "neutral" with respect to the source of the tone. This alteration
      of response selection operations eliminated the effect of the auditory cue.
      Findings, then, suggested that irrelevant information did not affect the stimulus
      encoding stage but, instead, affected the response selection stage of processing.

PMID- 23964574
TI  - Risk versus effort in the assessment of motor fatigue.
AB  - The choice of probability leffort (COPE) devices require fatigued subjects to
      choose between risk and effort. In a first experiment, where fatigue was induced
      by an intense or by a prolonged motor task and where the required effort was
      perceptual, the fatigue did not generalize to the test mode. A second experiment
      used motor fatigue of the arm or leg, and tested with arm muscle effort, showing
      that subjects fatigued with either limb chose riskier alternatives in order to
      avoid the effort. The data correlated with self-rated fatigue, and closely
      paralleled earlier work using perceptual fatigue and perceptual effort. 

PMID- 23964575
TI  - Intraindividual variability in development of accuracy of motor performance.
AB  - Age trends in children's ball-rolling accuracy were investigated with a
      concentration on intraindividual variability. The subjects were boys and girls (n
      =20 each) who were randomly selected from each of seven groupings representing
      ages 5 to 11 yr. Significant reduction in mean constant error occurred with
      increasing age for both sexes, and the boys performance was superior to that of
      the girls' across ages. The concept of modification of performance toward less
      variability was supported by significant reduction of mean intraindividual
      variance with age; however, the sex difference in mean intraindividual variance
      (greater consistency in boys' performance) was not constant over age. The results
      are discussed in relation to speculated cultural influences, and consideration is
      given to the importance of examining intraindividual variance in studies of age
      trends in motor performance. 

PMID- 23964576
TI  - Preparatory set, response complexity, and reaction latency.
AB  - The interaction between preparatory set and response complexity was demonstrated
      in an experiment investigating the reaction latency of discrete arm movements.
      Following simple finger-lift reaction-time (RT) trials, subjects performed simple
      and complex versions of a discrete horizontal arm movement under one of two
      enforced preparatory set conditions. For the simple task, requiring subjects to
      attend to the components of the response prior to stimulus presentation (enforced
      motor set) produced significantly shorter RTs than when concentration was on the
      stimulus (enforced sensory set). However, RT differences for the complex version
      of the task failed significance. Theoretical implications of the results for
      Henry's (1960) memory drum theory of neuromotor reaction were discussed. 

PMID- 23964577
TI  - Motor learning without knowledge of results through the development of a response
      recognition mechanism.
AB  - Four experiments were conducted to investigate the ability of a response
      recognition mechanism, developed by presenting the sensory consequences
      associated with the criterion movement in the absence of actual movement recall,
      to produce motor learning in the absence of knowledge of results (KR). In
      Experiments 1 and 2, a rapid linear timing task was used (10.16 cm in 100 msec),
      and reduction of movement error resulted over no-KR practice trials. Experiments
      3 and 4 employed a slow movement-time task (750 and 1250 msec) and a linear
      positioning task, respectively, and no reduction of movement error occurred over
      the no-KR practice trials in either experiment. The ability of the response
      recognition mechanism to produce motor learning in the absence of KR depended
      upon the extent to which feedback could be used during response production. 

PMID- 23964578
TI  - The interrelationships between anxiety, motor performance and electromyography.
AB  - Much confusion in the research on anxiety and motor behavior is due to the
      failure to distinguish between anxiety as a transitory state and as a relatively
      stable state. In addition, researchers have been focusing on the end result of a
      motor act (performance) instead of investigating the quality of movement
      (patterns of energy organization) that make up the motor act. The State-Trait
      Anxiety Inventory was administered in this study to distinguish A-State and A
      Trait subjects, while electromyography was used to investigate qualitative
      differences in motor behavior. High-anxious subjects performed significantly
      poorer than low-anxious subjects, and they used more energy over a longer period
      of time before, during, and after the performance than low-anxious subjects. The
      results were discussed in terms of efficiency of neuromuscular energy
      expenditure. 

PMID- 23964579
TI  - Application of the theory of signal detectability to kinesthetic discrimination
      tasks.
AB  - The psychophysical methods of the theory of signal detectability were applied to
      the measurement of kinesthetic recognition sensitivity. Subjects (n = 12) were
      tested on a kinesthetic discrimination apparatus, and were randomly assigned to
      one of four treatment conditions. Each subject operated under five response
      criteria which were imposed through a priori probabilities of high and low
      kinesthetic stimuli. The fundamental assumptions of the theory of signal
      detectability were tested and the basic premises of normality and equality of
      variance observed in most cases. A subproblem investigated the relationship
      between kinesthetic recognition sensitivity and the two independent variables of
      direction and extent of forearm movement, but no relationship was observed. This
      study was conducted at Kansas State University under the direction of Richard H.
      Cox with technical assistance from Harold L. Hawkins. The study was funded by a
      Faculty Research Grant awarded by Kansas State University. 

PMID- 23964580
TI  - Variability of practice and transfer of training.
AB  - Two experiments were conducted to test predictions, arising from Schmidt's (1975)
      schema theory of motor learning, related to the effect of variability of initial
      practice upon subsequent transfer to another task. Rapid linear timing movements
      were employed to operationally separate the recall and recognition schemata.
      Experiment 1 showed that training at two different movement times, when given in
      an appropriate order, facilitated the recall and recognition of a subsequent
      transfer movement-time task, but only when the criterion movement time was
      sufficiently outside the range of initial practice. Experiment 2 increased the
      number of training movement times beyond two, but no reliable transfer effect
      occurred, although the variable practice groups showed significantly reduction of
      movement error on the initial transfer trials in the absence of knowledge of
      results. Overall, the two experiments provided some initial support for Schmidt's
      schema theory of motor learning. Diane C. Shapiro is now at the Department of
      Physical Education, University of Southern California, Los Angeles, CA 90007. 

PMID- 23964581
TI  - The large pursuit rotor.
AB  - The question of whether certain phenomena that occur on the conventional rotary
      pursuit and other small apparatus also appear on a gross motor task was examined
      using a large pursuit rotor that required whole-body movements. College males
      (n=29) were given 90 10-sec trials over three consecutive days with 30 trials of
      continuous practice per day. The existence of reactive inhibition, reminiscence,
      and warmup decrement was confirmed, indicating that common mechanisms underlie
      both fine and gross bodily movements. In addition, the substantial amounts of
      learning and the high reliabilities for performance and learning indicated that
      the present apparatus has considerable potential for motor-learning research. 

PMID- 23964582
TI  - Photoisomerization action spectroscopy of the carbocyanine dye DTC+ in the gas
      phase.
AB  - Molecular photoisomerization plays a crucial role in diverse biological and
      technological contexts. Here, we combine ion mobility spectrometry and laser
      spectroscopy to characterize the photoisomerization of molecular cations in the
      gas phase. The target molecular ions, polymethine dye cations 3,3'
      diethylthiacarbocyanine (DTC(+)), are propelled through helium buffer gas by an
      electric field and are photoisomerized by light from a tunable laser.
      Photoexcitation over the 450-570 nm range converts trans-DTC(+) to cis-DTC(+),
      noticeably modifying the ions' arrival time distribution. The photoisomerization
      action spectrum, which has a maximum at 535 nm, resembles the absorption spectrum
      of DTC(+) in solution but is shifted 25 nm to shorter wavelength. Comparisons
      between measured and calculated mobilities suggest that the photoisomer involves
      a twist about the second C-C bond in the methine chain (8,9-cis isomer) rather
      than a twist about the first methine C-C bond (2,8-cis isomer). It is postulated
      that the excited gas-phase ions internally convert from the S1 Franck-Condon
      region to the S0 manifold and explore the conformational landscape as they cool
      through He buffer gas collisions. Master equation simulations of the relaxation
      process in the S0 manifold suggest that the 8,9-cis isomer is preferred over the
      2,8-cis isomer because it lies lower in energy and because it is separated from
      the trans isomer by a substantially higher barrier. The study demonstrates that
      the photoisomerization of molecular ions can be probed selectively in the gas
      phase, providing insights into photoisomerization mechanisms and information on
      the solvent-free absorption spectrum. 

PMID- 23964583
TI  - Gender differences in alcohol affection on an individual.
AB  - It is a well-known fact that after drinking the same amount of alcohol, women
      show more signs of the effects of alcohol than men of the same weight. It seems
      that the main factors responsible for sex differences in alcohol metabolism and
      influence are the relatively lower amount of body water related to body fat in
      women than men and lower gastric ADH activity in women, both of which enable
      women to reach higher BAC after drinking equivalent amounts of alcohol with men.
      On the other hand, first-pass metabolism of alcohol during passing through the
      liver is more rapid in women, probably due to bigger liver mass in women than in
      men. It is proven that alcohol and sex hormones have bilateral influence on each
      other. Women with more rapid alcohol elimination ability show higher levels of
      sex hormones in blood than the rest. It seems that the specific body constitution
      of the female organism as well as the unique combination of their sex hormones is
      responsible for the gender differences in alcohol influence. KEYWORDS: alcohol
      metabolism - gender differences - gastric ADH - blood alcohol concentration.

PMID- 23964584
TI  - Death due to Arrhythmogenic Right Ventricular Dysplasia: A case report.
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) is both a myocardial disease
      that predominantly affects the right ventricle (RV) and one of the major causes
      of sudden death in the young and athletes. A 28-year-old man with no signicant
      medical history, applied to an emergency department with feeling very ill. After
      his initial examinations, electrocardiography (ECG) showed ventricular extra
      systoles and he was recommended for admission to a cardiology polyclinic. The
      next day, his condition worsened and he was dead on arrival at the hospital. A
      histological examination of heart samples, which were obtained from the RV and
      LV, revealed the massive replacement of myocardium by fibrous and mature adipose
      tissue in the RV. In this case, there were no symptoms, family and medical
      history and its clinical presentation was as an unexpected sudden death.
      KEYWORDS: Arrhythmogenic right ventricular dysplasia, sudden cardiac death,
      autopsy.

PMID- 23964585
TI  - [Traumatic changes of intrathoracic organs due to external mechanical
      cardiopulmonary resuscitation. Case reports].
AB  - External mechanical resuscitation systems were developed for continuous and
      effective chest compression with the goal to increase the probability of
      spontaneous blood circulation renew. We describe results of four autopsy cases,
      where the external mechanical resuscitation by system Lucas (n=3) and AutoPulse
      (n=1) was performed prior to death. In all the cases were found traumatic changes
      which are commonly described in various studies such as skin abrasions on the
      chest, multiple rib fractures, fracture of the sternum and hematoma in the
      mediastinum or pericardium. In addition to these usual traumatic changes
      accompanying mechanical cardiopulmonary resuscitation we have observed injuries
      of intrathoracic organs, mainly the contusions of the heart and contusions and
      laceration of the lungs. In addition to these changes were in one case,
      associated with prolonged AutoPulse resuscitation, found ruptures of intima of
      the right common carotid artery. These injuries, with few exceptions, are not
      commonly described even over much wider number of examined persons. Injuries of
      the abdominal organs in connection with mechanical resuscitation, as described in
      a few case reports, were not present. However in one case there was found
      contusion of myocardium due to the external resuscitation by the Lucas system
      with clinical manifestation of sudden coronary incident even though the cause of
      death was massive thrombotic embolism to pulmonary arteries. All reported cases
      were similar in the relatively long-lasting mechanic cardiopulmonary
      resuscitation and prolonged time of dying of the patients. KEYWORDS:
      cardiopulmonary resuscitation - Lucas - AutoPulse - intrathoracic injury.

PMID- 23964586
TI  - Sudden death due to high take-off right coronary artery.
AB  - Reported case was 46-year-old woman found dead at the forest park rest area.
      Autopsy examination revealed grossly but normal in appearance heart weighed 400
      gr. The orifice of right coronary artery round in shape was situated in the
      ascending aorta; 17 mm above the sinotubular junction, there was a high take-off
      coronary artery with ectopic localization. Dissection of the artery confirmed
      that the proximal segment of the right coronary artery passed between the aorta
      and pulmonary artery, with acute, oblique down-ward angulation. We aimed to
      present the rare coronary anomaly and discuss the case from medico legal aspect.
      KEYWORDS: Sudden cardiac death - coronary artery - high take-off - ectopic -
      autopsy.

PMID- 23964587
TI  - Signs of self-inflicted wounds; how accurate they are.
AB  - KEYWORDS: self-inflicted wounds - forensic - signs.

PMID- 23964588
TI  - Insights into the European rabbit (Oryctolagus cuniculus) innate immune system:
      genetic diversity of the toll-like receptor 3 (TLR3) in wild populations and
      domestic breeds.
AB  - BACKGROUND: Toll-like receptors (TLRs) belong to the innate immune system and are
      a major class of pattern recognition receptors representing the first line of the
      innate immune response. The TLR molecule is structurally composed by an
      ectodomain that contains leucine rich repeats (LRRs) that interact with pathogen
      associated molecular patterns (PAMPs), a transmembrane domain and a conserved
      cytoplasmic domain designated TIR (Toll-IL1 receptor) that is responsible for the
      intracellular signaling. TLR3 has been associated with the direct recognition of
      double-stranded viral RNA resulting from viral replication, while TLR7 and TLR8
      target single-stranded viral RNA. In the European rabbit (Oryctolagus cuniculus),
      TLR7 and TLR8 were reported to be absent and pseudogenised, respectively, making
      TLR3 the only available TLR for the recognition of viral RNA. Thus, the levels of
      diversity of TLR3 were evaluated in the European rabbit by analysing different
      genetic backgrounds and exposure to pathogen pressures. RESULTS: We detected 41
      single nucleotide polymorphisms (SNPs) in the coding sequence of TLR3. The
      highest diversity was observed in the wild populations of Iberian Peninsula,
      between 22-33 polymorphic positions. In the French population, 18 SNPs were
      observed and only 4 polymorphic positions were detected in the domestic breeds.
      14 non-synonymous substitutions were observed, most of them in the LRR molecules.
      The remaining were scattered across the transmembrane and TIR domains.
      CONCLUSION: The study of TLR3 in European rabbit populations might be relevant to
      understand the interplay between RNA viruses and innate immunity. Wild rabbit
      populations presented more diversity than domestic breeds and other mammals
      previously studied. This might be linked to the absence of population bottlenecks
      during their evolution and to the almost inexistence of man-mediated selection.
      The observed variability might have also been potentiated by the contact of the
      wild populations with various pathogens. The study of these patterns of
      variability might reveal scenarios of host-pathogen interaction and identify TLR3
      polymorphisms' that arose due to viral pathogens affecting wild populations.

PMID- 23964589
TI  - Dietary patterns, metabolic markers and subjective sleep measures in resident
      physicians.
AB  - Shiftwork is common in medical training and is necessary for 24-h hospital
      coverage. Shiftwork poses difficulties not only because of the loss of actual
      sleep hours but also because it can affect other factors related to lifestyle,
      such as food intake, physical activity level, and, therefore, metabolic patterns.
      However, few studies have investigated the nutritional and metabolic profiles of
      medical personnel receiving training who are participating in shiftwork. The aim
      of the present study was to identify the possible negative effects of food
      intake, anthropometric variables, and metabolic and sleep patterns of resident
      physicians and establish the differences between genders. The study included 72
      resident physicians (52 women and 20 men) who underwent the following
      assessments: nutritional assessment (3-day dietary recall evaluated by the
      Adapted Healthy Eating Index), anthropometric variables (height, weight, body
      mass index, and waist circumference), fasting metabolism (lipids, cortisol, high
      sensitivity C-reactive protein [hs-CRP], glucose, and insulin), physical activity
      level (Baecke questionnaire), sleep quality (Pittsburgh Sleep Quality Index;
      PSQI), and sleepiness (Epworth Sleepiness Scale; ESS). We observed a high
      frequency of residents who were overweight or obese (65% for men and 21% for
      women; p = 0.004). Men displayed significantly greater body mass index (BMI)
      values (p = 0.002) and self-reported weight gain after the beginning of residency
      (p = 0.008) than women. Poor diet was observed for both genders, including the
      low intake of vegetables and fruits and the high intake of sweets, saturated fat,
      cholesterol, and caffeine. The PSQI global scores indicated significant
      differences between genders (5.9 vs. 7.5 for women and men, respectively; p =
      0.01). Women had significantly higher mean high-density lipoprotein cholesterol
      (HDL-C; p < 0.005), hs-CRP (p = 0.04), and cortisol (p = 0.009) values than men.
      The elevated prevalence of hypertriglyceridemia and abnormal values of low
      density lipoprotein cholesterol (LDL-C; >100 mg/dL) were observed in most
      individuals. Higher than recommended hs-CRP levels were observed in 66% of the
      examined resident physicians. Based on current recommendations, a high prevalence
      of low sleep quality and excessive daytime sleepiness was identified. These
      observations indicate the need to monitor health status and develop actions to
      reassess the workload of medical residency and the need for permission to perform
      extra night shifts for medical residents to avoid worsening health problems in
      these individuals.

PMID- 23964590
TI  - Novel highly sensitive, specific, and straightforward strategy for comprehensive
      N-terminal proteomics reveals unknown substrates of the mitochondrial peptidase
      Icp55.
AB  - We present a novel straightforward method for enrichment of N-terminal peptides,
      utilizing charge-based fractional diagonal chromatography (ChaFRADIC). Our method
      is robust, easy to operate, fast, specific, and more sensitive than existing
      methods, enabling the differential quantitation of 1459 nonredundant N-terminal
      peptides between two S. cerevisiae samples within 10 h of LC-MS, starting from
      only 50 MUg of protein per condition and analyzing only 40% of the obtained
      fractions. Using ChaFRADIC we compared mitochondrial proteins from wild-type and
      icp55Delta yeast (30 MUg each). Icp55 is an intermediate cleaving peptidase,
      which, following mitochondrial processing peptidase (MPP)-dependent cleavage of
      signal sequences, removes a single amino acid from a specific set of proteins
      according to the N-end rule. Using ChaFRADIC we identified 36 icp55 substrates,
      14 of which were previously unknown, expanding the set of known icp55 substrates
      to a total of 52 proteins. Interestingly, a novel substrate, Isa2, is likely
      processed by Icp55 in two consecutive steps and thus might represent the first
      example of a triple processing event in a mitochondrial precursor protein. Thus,
      ChaFRADIC is a powerful and practicable tool for protease and peptidase research,
      providing the sensitivity to characterize even samples that can be obtained only
      in small quantities. 

PMID- 23964591
TI  - Membrane undulation induced by NS4A of Dengue virus: a molecular dynamics
      simulation study.
AB  - Nonstructural protein 4A (NS4A) of Dengue virus (DENV) is a membrane protein
      involved in rearrangements of the endoplasmic reticulum membrane that are
      required for formation of replication vesicles. NS4A is composed most likely of
      three membrane domains. The N- and C-terminal domains are supposed to traverse
      the lipid membrane whereas the central one is thought to reside on the membrane
      surface, thus forming a u-shaped protein. All three membrane domains are proposed
      to be helical by secondary structure prediction programs. After performing multi
      nanosecond molecular dynamics (MD) simulations at various temperatures (300, 310,
      and 315.15 K) with each of the individual domains, they are used in a docking
      approach to define putative association motifs of the transmembrane domains
      (TMDs). Two structures of the u-shaped protein are generated by separating two
      assembled TMDs linking them with the membrane-attached domain. Lipid undulation
      is monitored with the structures embedded in a fully hydrated lipid bilayer
      applying multiple 200 ns MD simulations at 310 K. An intact structure of the
      protein supports membrane undulation. The strong unwinding of the helices in the
      domain-linking section of one of the structures lowers its capability to induce
      membrane curvature. Unwinding of the link region is due to interactions of two
      tryptophan residues, Trp-96 and 104. These results provide first insights into
      the membrane-altering properties of DENV NS4A.

PMID- 23964592
TI  - Wham, sock, kapow! Can Batman defeat his biggest foe yet and combat mental health
      discrimination? An exploration of the video games industry and its potential for
      health promotion.

PMID- 23964593
TI  - Intact priming for novel perceptual representations in amnesia.
AB  - Recent studies have challenged the notion that priming for ostensibly novel
      stimuli such as pseudowords (REAB) reflects the creation of new representations.
      Priming for such stimuli could instead reflect the activation of familiar memory
      representations that are orthographically similar (READ) and/or the activation of
      subparts of stimuli (RE, EX, AR), which are familar because they occur commonly
      in English. We addressed this issue in three experiments that assessed perceptual
      identification priming and recognition memory for novel and familiar letter
      strings in amnesic patients and control subjects. Priming for words, pseudowords,
      and orthographically illegal nonwords was fully intact in the amnesic patients
      following a single exposure, whereas recognition memory was impaired for the same
      items. Thus, priming can occur for stimuli that are unlikely to have preexisting
      representations. Words and pseudowords exhibited twice as much priming as illegal
      nonwords, suggesting that activation may contribute to priming for words and
      wordlike stimuli. Additional results showed that priming for illegal nonwords
      resulted from the formation of new perceptual associations among the component
      letters of each nonword rather than the activation of individual letter
      representations. In summary, the results demonstrate that priming following a
      single exposure can depend on the creation of new perceptual representations and
      that such priming is independent of the brain structures essential for
      declarative memory. 

PMID- 23964594
TI  - Semantic repetition priming for verbal and pictorial knowledge: a functional MRI
      study of left inferior prefrontal cortex.
AB  - Functional neuroimaging studies of single-word processing have demonstrated
      decreased activation in left inferior prefrontal cortex (LIPC) during repeated
      semantic processing relative to initial semantic processing. This item-specific
      memory effect occurs under implicit test instructions and represents word-toword
      semantic repetition priming. The present study examined the stimulus generality
      of LIPC function by measuring prefrontal cortical activation during repeated
      relative to initial semantic processing of words (word-to-word semantic
      repetition priming) and of pictures (picture-to-picture semantic repetition
      priming). For both words and pictures, LIPC activation decreased with repetition,
      suggesting that this area subserves semantic analysis of stimuli regardless of
      perceptual form. Decreased activation was greater in extent for words than for
      pictures. The LIPC area may act as a semantic executive system that mediates on
      line retrieval of long-term conceptual knowledge necessary for guiding task
      performance. 

PMID- 23964595
TI  - Segregating Semantic from Phonological Processes during Reading.
AB  - A number of previous functional neuroimaging studies have linked activation of
      the left inferior frontal gyms with semantic processing, yet damage to the
      frontal lobes does not critically impair semantic knowledge. This study
      distinguishes between semantic knowledge and the strategic processes required to
      make verbal decisions. Using positron emission tomography (PET), we identify the
      neural correlates of semantic knowledge by contrasting semantic decision on
      visually presented words to phonological decision on the same words. Both tasks
      involve identical stimuli and a verbal decision on central lingual codes
      (semantics and phonology), but the explicit task demands directed attention
      either to meaning or to the segmentation of phonology. Relative to the
      phonological task, the semantic task was associated with activations in left
      extrasylvian temporal cortex with the highest activity in the left temporal pole
      and a posterior region of the left middle temporal cortex (BA 39) close to the
      angular gyrus. The reverse contrast showed increased activity in both
      supramarginal gyri, the left precentral sulcus, and the cuneus with a trend
      toward enhanced activation in the inferior frontal cortex. These results fit well
      with neuropsychological evidence, associating semantic knowledge with the
      extrasylvian left temporal cortex and the segmentation of phonology with the
      perisylvian cortex. 

PMID- 23964596
TI  - Visual imagery: effects of short- and long-term memory.
AB  - Visual imagery and perception share several functional properties and apparently
      share common underlying brain structures. A main approach to the scientific study
      of visual imagery is exploring the effects of mental imagery on perceptual
      processes. Previous studies have shown that visual imagery interferes with
      perception (Perky effect). Recently we have shown a direct facilitatory effect of
      visual imagery on visual perception. In an attempt to differentiate the
      conditions under which visual imagery interferes or facilitates visual
      perception, we designed new experimental paradigms, using detection tasks of a
      Gabor target. We found that imagery-induced interference and facilitation are
      memorydependent: Visual recall of common objects from long-term memory can
      interfere with perception, while on short-term memory tasks facilitation can be
      obtained. These results support the distinction between low-level and structural
      representations in visual memory. 

PMID- 23964597
TI  - Effects of memory load and distraction on performance and event-related slow
      potentials in a visuospatial working memory task.
AB  - Brain electrical activity related to working memory was recorded at 15 scalp
      electrodes during a visuospatial delayed response task. Participants (N = 18)
      touched the remembered position of a target on a computer screen after either a 1
      or 8 sec delay. These memory trials were compared to sensory trials in which the
      target remained present throughout the delay and response periods. Distractor
      stimuli identical to the target were briefly presented during the delay on 30% of
      trials. Responses were less accurate in memory than sensory trials, especially
      after the long delay. During the delay slow potentials developed that were
      significantly more negative in memory than sensory trials. The difference between
      memory and sensory trials was greater at anterior than posterior electrodes. On
      trials with distractors, the slow potentials generated by memory trials showed
      further enhancement of negativity, whereas there were minimal effects on accuracy
      of performance. The results provide evidence that engagement of visuospatial
      working memory generates slow wave negativity with a timing and distribution
      consistent with frontal activation. Enhanced brain activity associated with
      working memory is required to maintain performance in the presence of
      distraction. 

PMID- 23964598
TI  - Word, pseudoword, and nonword processing: a multitask comparison using event
      related brain potentials.
AB  - Event-related brain potentials (ERPs) to words, pseudowords, and nonwords were
      recorded in three different tasks. A letter search task was used in Experiment 1.
      Performance was affected by whether the target letter occurred in a word, a
      pseudoword, or a random nonword. ERP results corroborated the behavioral results,
      showing small but reliable ERP differences between the three stimulus types.
      Words and pseudowords differed from nonwords at posterior sites, whereas words
      differed from pseudowords and nonwords at anterior sites. Since deciding whether
      the target letter was present or absent co-occurred with stimulus processing in
      Experiment 1, a delayed letter search task was used in Experiment 2. ERPs to
      words and pseudowords were similar and differed from ERPs to nonwords, suggesting
      a primary role of orthographic and phonological processing in the delayed letter
      search task. To increase semantic processing, a categorization task was used in
      Experiment 3. Early differences between ERPs to words and pseudowords at left
      posterior and anterior locations suggested a rapid activation of lexico-semantic
      information. These findings suggest that the use of ERPs in a multiple task
      design makes it possible to track the time course and the activation of multiple
      sources of linguistic information when processing words, pseudowords, and
      nonwords. The task-dependent nature of the effects suggests that the language
      system can use multiple sources of linguistic information in flexible and
      adaptive ways. 

PMID- 23964599
TI  - Individual Differences in Inference Generation: An ERP Analysis.
AB  - Readers routinely draw inferences with remarkable efficiency and seemingly little
      cognitive effort. The present study was designed to explore different types of
      inferences during the course of reading, and the potential effects of differing
      levels of working memory capacity on the likelihood that inferences would be
      made. The electroencephalogram (EEG) was recorded from five scalp sites while
      participants read 90 paragraphs, composed of 60 experimental paragraphs and 30
      filler paragraphs. Each experimental paragraph was four sentences long, and the
      final sentence stated explicitly the inference that readers did or did not make.
      There were four types of experimental paragraphs: (1) Bridging inference, (2)
      Elaborative inference, (3) Word-Based Priming control, and (4) No Inference
      control. Participants were tested using the Daneman and Carpenter (1980) Reading
      Span Task and categorized as having low or high working memory capacity. The
      average peaks of the N400 component of the event-related brain potential (EM)
      were used as a measure of semantic priming and integration, such that the lower
      the N400 was in response to the explicitly stated inference concept, the more
      likely it was that the reader made the inference. Results indicate that readers
      with high working memory capacity made both bridging (necessary) and elaborative
      (optional) inferences during reading, whereas readers with low working memory
      capacity made only bridging inferences during reading. We interpret the findings
      within the framework of the Capacity Constrained Comprehension model of Just and
      Carpenter (1992). 

PMID- 23964600
TI  - Event-related brain potentials following incorrect feedback in a time-estimation
      task: evidence for a "generic" neural system for error detection.
AB  - We examined scalp-recorded event-related potentials following feedback stimuli in
      a time-estimation task. Six hundred msec after indicating the end of a 1 sec
      interval, subjects received a visual, auditory, or somatosensory stimulus that
      indicated whether the interval they had produced was correct. Following feedback
      indicating incorrect performance, a negative deflection occurred, whose
      characteristics corresponded closely to those of the component (the error-related
      negativity) that accompanies errors in choice reaction time tasks. Furthermore,
      equivalent dipole analysis suggested that, for all three modalities, the
      distribution of the scalp potential was consistent with a local source in the
      anterior cingulate cortex or a more distributed source in the supplementary motor
      areas. These loci correspond closely to those described previously for the error
      related negativity. We conclude that the error-related negativity is the
      manifestation of the activity of a "generic" neural system involved in error
      detection. 

PMID- 23964601
TI  - Localization of auditory evoked potentials related to selective intermodal
      attention.
AB  - A long-standing question in attention research is the extent to which selection
      involves gates in the sensory stream and the extent to which they involve added
      secondary processes. Intermodal attention paradigms are useful for examining this
      issue since different modalities involve readily distinguished cortical regions.
      Evoked potential studies have identified an attention-related frontal negativity
      labeled the Nd in auditory attention studies. It has been suggested that it
      arises from modulation of the auditory cortex (compatible with gating mechanisms)
      or of the frontal cortex (compatible with secondary processes such as short-term
      memory buffers). Efforts to localize the Nd have been impaired by the finding
      that the Nd comprises multiple components. Some novel procedures utilizing
      principal components analysis, in conjunction with high-density 64-channel
      recordings, were used to address this issue. Results suggest that the major
      source of the early Nd (the portion of most interest) resides in the frontal
      cortex, supporting the secondary process view for this particular mechanism. 

PMID- 23964602
TI  - Coordinate frame for pattern recognition in unilateral spatial neglect.
AB  - The present research examines the effect of spatial (object-centered) attentional
      constraints on pattern recognition. Four normal subjects and two right-hemisphere
      damaged patients with left visual neglect participated in the study. Small,
      letterlike, prelearned patterns served as stimuli. Short exposure time prevented
      overt scanpaths during stimulus presentation. Attention was attracted to a
      central (midsagittal) hation point by precuing this location prior to each
      stimulus presentation. Minute (up to 1.5 degrees  of visual angle) rightward and
      leftward stimulus shifts caused attention to be allocated each time to a
      different location on the object space, while remaining in a fixed central
      position in viewercentered coordinates. The task was to decide which of several
      prelearned patterns was presented in each trial. In the normal subjects, best
      performance was achieved when the luminance centroid (LC; derived from the
      analysis of low-spatial frequencies in the object space) of each pattern
      coincided with the spatial position of the precue. In contrast, the patients with
      neglect showed optimal recognition performance when precuing attracted attention
      to locations within the object space, to the left of the LC. The normal
      performance suggests that the LC may serve as a center of gravity for attention
      allocation during pattern recognition. This point seems to be the target location
      where focal attention is normally directed, following a primary global analysis
      based on the low spatial frequencies. Thus, the LC of a simple pattern may serve
      as the origin point for an object-centered-coordiate-frame (OCCF), dividing it
      into right and left. This, in turn, serves to create a prototype description of
      the pattern, in its own coordinates, in memory, to be addressed during subsequent
      recognition tasks. The best match of the percept with the stored description may
      explain the observed advantage of allocating attention to the LC. The performance
      of the brain- damaged patients can be explained in terms of neglect operating in
      the OCCE. 

PMID- 23964603
TI  - A Developmental Functional MRI Study of Prefrontal Activation during Performance
      of a Go-No-Go Task.
AB  - This study examines important developmental differences in patterns of activation
      in the prefrontal cortex during performance of a Go-No-Go paradigm using
      functional magnetic resonance imaging (fMRI). Eighteen subjects (9 children and 9
      adults) were scanned using gradient echo, echo planar imaging during performance
      of a response inhibition task. The results suggest four general findings. First,
      the location of activation in the prefrontal cortex was not different between
      children and adults, which is similar to our earlier pediatric fMRI results of
      prefrontal activation during a working memory task (Casey et al., 1995). Second,
      the volume of activation was significantly greater for children relative to
      adults. These differences in volume of activation were observed predominantly in
      the dorsal and lateral prefrontal cortices. Third, although inhibitory processes
      have typically been associated with more ventral or orbital frontal regions, the
      current study revealed activation that was distributed across both dorsolateral
      and orbitofrontal cortices. Finally, consistent with animal and human lesion
      studies, activity in orbital frontal and anterior cingulate cortices correlated
      with behavioral performance (i.e., number of false alarms). These results further
      demonstrate the utility of this methodology in studying pediatric populations. 

PMID- 23964604
TI  - Infants Attribute Value+/- to the Goal-Directed Actions of Self-propelled
      Objects.
AB  - Motion is a fundamental source of information for basic human interpretations; it
      is basic to the fundamental concept of causality and, the present model argues,
      equally basic to the fundamental concept of intentionality. The model is based on
      two main assumptions: When an infant perceives an object (1) moving spontaneously
      and (2) displaying goaldirected action, it will interpret the object as
      intentional and assign to it the unique properties of the psychological domain.
      The key property tested was: Do infants attribute value to interactions between
      intentional objects using criteria specified by the model? We showed infants
      (average age 52 weeks) computer-generated animations of spontaneously moving
      "balls," using looking time in a standard habituation/dishabituation paradigm. In
      two positive interactions, one ball either "caressed" another, or "helped" it
      achieve its goal; whereas in two negative interactions, one ball either "hit"
      another, or "prevented" it from achieving its goal. In keeping with predictions
      of the model, when transferred to a negative condition, infants who had been
      habituated on a positive condition showed greater dishabituation than those
      habituated on a negative condition. The results could not be easily explained by
      the similarity relations among the animations depicting the interactions. The
      results suggest that well before the age when the child can ascribe mental states
      or has a "theory of mind," it recognizes the goals of self-propelled objects and
      attributes value to the interactions between them. 

PMID- 23964606
TI  - Significant enhancement of energy barriers in dinuclear dysprosium single
      molecule magnets through electron-withdrawing effects.
AB  - The effect of electron-withdrawing ligands on the energy barriers of Single
      Molecule Magnets (SMMs) is investigated. By introducing highly electron
      withdrawing atoms on targeted ligands, the energy barrier was significantly
      enhanced. The structural and magnetic properties of five novel SMMs based on a
      dinuclear {Dy2} phenoxo-bridged motif are explored and compared with a previously
      studied {Dy2} SMM (1). All complexes share the formula
      [Dy2(valdien)2(L)2].solvent, where H2valdien = N1,N3-bis(3-methoxysalicylidene)
      diethylenetriamine, the terminal ligand L = NO3(-) (1), CH3COO(-) (2), ClCH2COO(
      ) (3), Cl2CHCOO(-) (4), CH3COCHCOCH3(-) (5), CF3COCHCOCF3(-) (6), and solvent =
      0.5 MeOH (4), 2 CH2Cl2 (5). Systematic increase of the barrier was observed for
      all complexes with the most drastic increase seen in 6 when the acac ligand of 5
      was fluorinated resulting in a 7-fold enhancement of the anisotropic barrier. Ab
      initio calculations reveal more axial g tensors as well as higher energy first
      excited Kramers doublets in 4 and 6 leading to higher energy barriers for those
      complexes. 

PMID- 23964607
TI  - Luis Felipe Fajardo L-G, MD, 1927-2013.

PMID- 23964608
TI  - The exocyclic olefin geometry control via Ireland-Claisen rearrangement:
      stereoselective total syntheses of Barmumycin and Limazepine E.
AB  - Stereoselective total syntheses of Limazepine E and Barmumycin, potent, naturally
      occurring antitumor agents, are described. The total syntheses control the olefin
      geometry via a highly selective chelation-controlled Ireland-Claisen
      rearrangement of a seven-membered lactone-derived boron enolate for the synthesis
      of (E)-4-ethylidene proline, a crucial building block for a number of natural
      products. 

PMID- 23964609
TI  - The role of pre-junctional D2 -like receptors mediating quinpirole-induced
      inhibition of the vasodepressor sensory CGRPergic out-flow in pithed rats.
AB  - Calcitonin gene-related peptide (CGRP) released from perivascular sensory nerves
      plays a role in the regulation of vascular tone. Indeed, electrical stimulation
      of the perivascular sensory out-flow in pithed rats produces vasodepressor
      responses, which are mainly mediated by CGRP release. This study investigated the
      potential role of dopamine D1 -like and D2 -like receptors in the inhibition of
      these vasodepressor responses. For this purpose, male Wistar pithed rats (pre
      treated i.v. with 25 mg/kg gallamine and 2 mg/kg min. hexamethonium) received
      i.v. continuous infusions of methoxamine (20 MUg/kg min.) followed by
      physiological saline (0.02 ml/min.), the D1 -like receptor agonist SKF-38393 (0.1
      1 MUg/kg min.) or the D2 -like receptor agonist quinpirole (0.03-10 MUg/kg min.).
      Under these conditions, electrical stimulation (0.56-5.6 Hz; 50 V and 2 ms) of
      the thoracic spinal cord (T9 -T12 ) resulted in frequency-dependent vasodepressor
      responses which were (i) unchanged during the infusions of saline or SKF-38393
      and (ii) inhibited during the infusions of quinpirole (except at 0.03 MUg/kg
      min.). Moreover, the inhibition induced by 0.1 MUg/kg min. quinpirole (which
      failed to inhibit the vasodepressor responses elicited by i.v. bolus injections
      of exogenous alpha-CGRP; 0.1-1 MUg/kg) was (i) unaltered after i.v. treatment
      with 1 ml/kg of either saline or 5% ascorbic acid and (ii) abolished after 300
      MUg/kg (i.v.) of the D2 -like receptor antagonists haloperidol or raclopride.
      These doses of antagonists (enough to completely block D2 -like receptors)
      essentially failed to modify per se the electrically induced vasodepressor
      responses. In conclusion, our results suggest that quinpirole-induced inhibition
      of the vasodepressor sensory CGRPergic out-flow is mainly mediated by pre
      junctional D2 -like receptors.

PMID- 23964610
TI  - Using ibuprofen to treat croup in six children presented to an emergency unit.

PMID- 23964612
TI  - The axiological ontology of occupational therapy: a philosophical analysis.
AB  - OBJECTIVE: This article describes the results of a study analyzing several
      discourses on the values of occupational therapy and some philosophical
      assumptions upon which these values are based. METHOD: A qualitative study of
      several values statements using the hermeneutical method--a conventional
      analytical approach in philosophy--was conducted. RESULTS: The literature review
      reveals that opinions on the values of occupational therapy differ greatly--no
      one value is shared among all the values statements examined. However, the
      majority of the texts mention occupational participation. A philosophical
      analysis of the literature shows that this value is based on a conception of
      human beings that can be traced back to the philosophical anthropologies of
      thinkers like Marx, Rousseau, Sartre, and Kant. The philosophical analysis also
      brought to light a certain conceptual confusion about what a value is.
      CONCLUSIONS: This article therefore offers some conceptual clarifications to help
      distinguish between values, beliefs, attitudes, principles, and non-evaluative
      concepts. It also presents the implications for practice of this philosophical
      analysis of values statements of the profession.

PMID- 23964611
TI  - Cord blood neutrophils display a galectin-3 responsive phenotype accentuated by
      vaginal delivery.
AB  - BACKGROUND: Term neonates are at increased risk of infections due to undeveloped
      immune mechanisms, and proper neutrophil function is important for perinatal
      immune defence. Galectin-3, an endogenous beta-galactoside-binding lectin, is
      emerging as an inflammatory mediator and we have previously shown that
      primed/activated, but not resting, adult neutrophils respond to this lectin by
      production of reactive oxygen species (ROS). We investigated if galectin-3 is of
      importance in perinatal immune defence, focusing on plasma levels and neutrophil
      responsiveness. METHODS: Neutrophils were isolated from peripheral blood of
      healthy adults and cord blood (CB) after elective Caesarean section (CSCB) and
      vaginal delivery (VDCB). ROS production was measured by chemiluminescence, L
      selectin expression by flow cytometry, and interleukin-8 (IL-8) and galectin-3
      concentrations by ELISA. Statistical evaluations were performed using the Mann
      Whitney test. RESULTS: In response to galectin-3, CSCB neutrophils showed a small
      but clear ROS production not evident in adult cells, signifying that neonatal
      neutrophils exist in a primed state. IL-8 production was elevated in CSCB cells
      while L-selectin exposure was equal to adult cells. Comparing CSCB to VDCB
      neutrophils, the latter showed an extensive galectin-3 responsiveness, indicating
      that the degree of priming is dependent on mode of delivery. VDCB neutrophils
      were increasingly prone to shed L-selectin, while the amount of IL-8 was similar
      to CSCB cells. The endogenous galectin-3 levels were higher in neonatal as
      compared to adult plasma, unaffected by mode of delivery. CONCLUSIONS:
      Neutrophils enter a pre-primed state already in the fetus. Upon exposure to the
      inflammatory stimuli that are associated with labor, the neutrophils develop a
      reactive phenotype with extensive priming features.

PMID- 23964613
TI  - Examination of why some community pharmacists do not provide 72-hour emergency
      prescription drugs to Medicaid patients when prior authorization is not
      available.
AB  - BACKGROUND: Existing federal law requires that a 72-hour emergency supply of a
      prescription drug be dispensed to Medicaid patients when prior authorization (PA)
      is not available and the medication is needed without delay. The pharmacist's
      role is to contact prescribers and inform them that PA is needed. If the
      prescriber cannot be reached, the pharmacist can dispense a 72-hour emergency
      supply. OBJECTIVES: To determine (a) the reasons why some community pharmacy
      owners/managers, staff pharmacists, and technicians are not compliant with the
      law; (b) how often the decision is made; and (c) estimate how often pharmacies do
      not dispense the 72-hour emergency supply when PA is not available. METHODOLOGY:
      A questionnaire was mailed to selected Texas community pharmacies. The instrument
      was developed by the researcher and reviewed by the Texas Medicaid Vendor Drug
      Program staff. The University of Texas, Office of Survey Research collected the
      data in September and October of 2011 by mail and online. The data were forwarded
      to the researcher for analyses. A total of 788 identified community pharmacies
      were mailed a packet containing 3 questionnaires to be completed by the
      pharmacist-in-charge, a staff pharmacist, and a pharmacy technician. There were 2
      mailings of the questionnaire packet and follow-up telephone calls to
      nonrespondents. RESULTS: A total of 653 questionnaires were completed and
      returned from 288 community pharmacies (36.7%) out of 788 pharmacies that were
      mailed the questionnaire packets. A total of 368 (57.5%) completed questionnaires
      came from chain store pharmacy respondents and 272 (42.5%) questionnaires from
      independent pharmacy respondents. A total of 21.3% (n = 134) of the respondents
      indicated that they were not aware of the federal and state requirement to
      dispense a 72-hour emergency supply of a prescription drug to Medicaid patients
      when prior authorization (PA) is not available. A greater proportion of the chain
      store respondents (26.6%) were unaware of the requirement compared with the
      independent pharmacy respondents (14.3%). A total of 77.7% of the respondents
      estimated that they make the decision of providing or not providing a 72-hour
      emergency supply of medication 6 or fewer times a month. A total of 14.6%
      indicated that they make the decision 6 to 11 times a month, and 7.7% make the
      decision more than 11 times a month. When asked how often respondents had seen a
      72-hour emergency prescription not being dispensed for Texas Medicaid recipients
      when PA was not available, 49.1% answered "never"; however, 30.0% indicated once
      or twice a month, 16.5% indicated from 1 to 5 times a week, and another 4.5%
      indicated more than 5 times a week. The top 2 reasons for not dispensing a 72
      hour-emergency drug supply were: "Reluctant to open a new 'unit-of-use' container
      (especially 30-day supply bottles)" and "The Rx will most likely be changed with
      the PA call, so why dispense a 72-hour supply of the originally prescribed drug?"
      The top categories of 72-hour emergency prescription drug products that
      respondents would "likely" dispense were antibiotics; inhaler canisters; products
      for nausea/vomiting, cough, and cold; antiseizure agents; and diabetic treatment
      products. CONCLUSIONS: The results show that there are many factors why
      pharmacists do not provide 72-hour emergency medications when PA is unavailable.
      The lack of awareness of the federal and state requirements was significantly
      related to the frequency of 72-hour medications not being dispensed. In addition,
      other factors inhibiting the process were the pharmacists' inability to reach
      physicians or the lack of cooperation with physicians, prescriptions for
      controlled substances, drug-packing limitations, and the financial risk involved
      with dispensing a 72-hour supply.

PMID- 23964614
TI  - Pharmacy students teaching prescribers strategies to lower prescription drug
      costs for underserved patients.
AB  - BACKGROUND: The rising costs of health care and, in particular, prescription
      drugs remains a challenge. Health professionals' ability to promote cost
      effective prescription drug use is critical, yet this subject is not included
      consistently in the curriculum of most health professional schools. As experts in
      prescription drug selection, use, and cost, pharmacists are in a unique position
      to help manage prescription drug regimens for the best therapeutic outcome, while
      also helping to keep patients' out-of-pocket (OOP) prescription drug costs low.
      In addition to promoting interprofessional collaboration, pharmacy student-led
      lectures may provide an effective means to teach prescription drug cost-savings
      strategies to other health professional students and current prescribers.
      OBJECTIVE: To describe and evaluate the impact of a 60- to 90-minute
      standardized, case-based lecture on prescribers' attitudes and knowledge about
      drug cost-containment strategies. METHODS: Four trained pharmacy students
      delivered a lecture that focused on strategies to help underserved patients with
      their OOP prescription drug costs. This lecture was given to health professional
      students and prescribers across disciplines. For purposes of this study,
      underserved patients included those with no drug insurance, those with limited
      financial resources who were unable to pay for their prescription drugs, and
      those whose drug insurance had significant gaps in coverage (e.g., Medicare Part
      D patients). Lectures targeted future and current prescribers and were delivered
      in multiple settings (e.g., residents' seminars, medical grand rounds, required
      health policy courses for medical and nursing students). Pretest/posttest surveys
      were administered to assess the impact of the lecture on learners' (a) knowledge
      of strategies to improve underserved patients' access to needed prescription
      drugs; (b) willingness to address and discuss cost issues with patients; (c)
      likelihood of collaborating with other health care professionals; and (d)
      perception of pharmacists as patient advocates. The survey collected demographic
      information about learners and assessed their knowledge through 5 case-based,
      multiple-choice questions. The survey also asked learners to rate their agreement
      with 5 statements using a 4-point Likert rating scale (4 = strongly agree to 1 =
      strongly disagree). To control for potential test-retest bias for the case-based
      knowledge questions, an alternate version of the pretest/posttest survey was
      developed without the pretest knowledge questions included. Learners received
      either 1 of the 2 surveys randomly before the lecture began and were instructed
      to complete the pretest portion of the survey before the start of the lecture and
      to complete the posttest portion of the survey at the conclusion of the lecture.
      RESULTS: From October 2010 to June 2012, trained pharmacy students delivered 19
      presentations to 626 learners from other health professions. Compared with the
      baseline, there was a statistically significant increase in the proportion of
      correct answers for each knowledge-based question after delivery of the lecture
      (overall significance P less than 0.001). Furthermore, there was a significant
      increase in the proportion of learners responding that they were more confident
      in their ability to select prescription drug cost-saving strategies; more likely
      to consult with other providers to lower OOP prescription drug costs; more likely
      to consider costs when making prescribing decisions; and more likely to ask their
      patients about prescription drug affordability (overall significance of P less
      than 0.05). In addition, after the lecture, more learners felt that pharmacists
      were patient advocates. Finally, 96% of learners felt that the lecture promoted
      interprofessional collaboration and would recommend it to other health care
      professionals. CONCLUSIONS: This study demonstrates that a single lecture given
      by pharmacy students to other health care professional students and current
      prescribers can improve knowledge of prescription drug cost-saving strategies
      targeted toward vulnerable patient populations and may increase the likelihood of
      collaboration between prescribers and pharmacists. The format of this lecture is
      an efficient and effective way to disseminate important and timely policy
      information to health care professionals.

PMID- 23964615
TI  - Health plan utilization and costs of specialty drugs within 4 chronic conditions.
AB  - BACKGROUND: Drugs are most typically defined as specialty because they are
      expensive; however, other criteria used to define a drug as specialty include
      biologic drugs, the need to inject or infuse the drug, the requirement for
      special handling, or drug availability only via a limited distribution network.
      Specialty drugs play an increasingly important role in the treatment of chronic
      conditions such as multiple sclerosis (MS), rheumatoid arthritis (RA), psoriasis,
      and inflammatory bowel disease (IBD), yet little is known regarding the
      comprehensive medical and pharmacy benefit utilization and cost trends for these
      conditions. OBJECTIVE: To describe MS, RA, psoriasis, and IBD trends for
      condition prevalence, treatment with specialty drugs, specialty costs,
      nonspecialty costs, and total direct costs of care within the medical and
      pharmacy benefits. METHODS: This was a descriptive analysis of a commercially
      insured population made up of 1 million members, using integrated medical and
      pharmacy administrative claims data from 2008 to 2010. Analyses were limited to
      continuously enrolled commercially insured individuals less than 65 years of age.
      Condition-specific cohorts for MS, RA, psoriasis, and IBD were defined using
      standardized criteria. Trends in condition prevalence, specialty drug use for the
      conditions, and direct total cost of care were analyzed. The direct costs were
      subcategorized into the following: medical benefit specialty drug costs, medical
      benefit all other costs, pharmacy benefit specialty drug costs, and pharmacy
      benefit all other costs. Trends and compound annual growth rates were calculated
      for the total cost of care and subcategory costs from 2008 through 2010. RESULTS:
      Condition prevalence ranged from a low of 1,720 per million members for MS to a
      high of 4,489 per million members for RA. Psoriasis and MS condition prevalence
      rates were unchanged over the 3 years; however, IBD prevalence increased 7.0%,
      and RA prevalence increased 9.7%. The rate of specialty drug use was lowest for
      IBD (13.7%) and highest for MS (71.8%). The lowest total annual cost of care was
      for psoriasis ($14,815), and the highest total annual cost was for MS ($36,901).
      The most commonly used specialty drugs for each of the conditions were as
      follows: glatiramer (MS), etanercept (RA and psoriasis), and infliximab (IBD).
      The total annual costs were more than double for the specialty drug users for
      psoriasis compared with all the psoriasis members ($29,565 vs. $14,815). The
      total costs were only somewhat higher among MS members using specialty drugs
      ($41,760 vs. $36,901). Among specialty drug users for each of the cohorts, the
      annual costs of specialty drugs accounted for 50% or more of the total annual
      costs. The annual spending growth rate for specialty drugs ranged from 4.4% to
      18.0%. CONCLUSIONS: Although specialty drug utilization varied widely across the
      4 chronic conditions analyzed, when specialty drugs were used they accounted for
      the majority of the annual total direct cost of care. Because specialty drugs are
      accounting for a growing portion of chronic disease total cost of care, health
      insurers will need to become more vigilant regarding specialty drug use and focus
      on 4 cost saving management opportunities: drug distribution channel, utilization
      management, contracting activities, and care coordination.

PMID- 23964616
TI  - Effect of an educational outreach program on prescribing potential drug-drug
      interactions.
AB  - BACKGROUND: The topic of improving prescribing practices is a major focus of many
      national initiatives, not only to enhance the quality of health care but also to
      reduce medical care costs. Educational outreach (also known as academic
      detailing) is a type of postgraduate education where trained clinical consultants
      meet face-to-face with prescribers to provide one-on-one information. Ideally,
      such visits promote evidence-based knowledge, create trusting relationships, and
      induce practice change, particularly with regard to prescribing potentially
      interacting medications. OBJECTIVE: To evaluate the effect of an educational
      outreach program delivered by clinical pharmacists on reducing the rate of
      prescribing potential drug-drug interactions (DDIs). METHODS: The intervention
      was a prescriber-directed educational outreach program focused on 25 clinically
      important DDIs. The effect of the educational outreach was evaluated using a
      retrospective pre-post study design with a control group was conducted. A total
      of 19,606 prescribers were educated on the DDIs of interest. A control group of
      19,606 prescribers, matched on prescribing volume and who did not receive the
      educational session were selected. Multivariate regression models were used to
      assess the impact of the educational program on the rate of prescribing potential
      DDIs. RESULTS: The 2 groups were significantly different with respect to age,
      profession, specialty, and geographic region. At baseline, mean DDI rates per 100
      drug prescriptions were 0.8 and 0.7 for prescribers who received the educational
      session and those who did not, respectively. Following delivery of the
      educational outreach program, mean potential DDI rates increased to 1.46 and 1.53
      per 100 precipitant drug prescriptions, an increase of 13.9% and 9.15% for the
      intervention and control groups, respectively. CONCLUSION: The current study was
      not able to demonstrate a significant beneficial effect of the educational
      outreach program on reducing the rate of prescribing potential DDIs.

PMID- 23964617
TI  - Impact of a combined pharmacist and social worker program to reduce hospital
      readmissions.
AB  - BACKGROUND: The Patient Protection and Affordable Care Act (2010) directed the
      Centers for Medicare and Medicaid Services to implement a hospital readmissions
      reduction program that reduces payments to hospitals for excess readmissions that
      began in October 2012. As such, hospitals across the country have been trying to
      identify and implement successful strategies for reducing hospitalizations.
      OBJECTIVE: To evaluate the impact of a combined pharmacist and social worker
      program on reducing 30-day, all-cause readmission rates to the same hospital.
      METHODS: Our study design was a retrospective, cross-sectional study that
      included 100 inpatients discharged from a large academic medical center. Fifty
      patients were enrolled in the combined pharmacist and social worker program, and
      50 received usual care; all were deemed high risk for readmission due to clinical
      or social factors. In the program group, a pharmacist performed a thorough
      medication history and review of discharge medications and, in some cases,
      communicated with the patient after discharge. The program group was also
      followed by a social worker team in the hospital and after discharge; as
      necessary, psychosocial interventions were performed. RESULTS: The 2 patient
      cohorts had similar demographic and clinical characteristics. Ten percent of
      patients enrolled in the combined pharmacist and social worker program were
      readmitted to the hospital for any reason within 30 days of discharge, compared
      with 30% of patients in the usual care group (P = 0.012). CONCLUSION: The
      combined pharmacist and social worker program demonstrated a significant
      reduction in 30-day, all-cause readmission rates to the same hospital.

PMID- 23964618
TI  - Attitudes of Medicare-eligible Americans toward mail service pharmacy.
AB  - BACKGROUND: For many years, community pharmacies provided mail delivery as a
      convenience for a small segment of special circumstance patients who requested
      it. Fueled by a movement among plan sponsors and prescription benefit managers to
      encourage or require its use, growth in mail service pharmacy began to accelerate
      in the 1980s and now accounts for nearly 25% of the market in the general
      population and a much higher percentage of seniors. OBJECTIVE: To assess the
      attitudes of Medicare-eligible Americans toward concerns that have been raised
      about mail service pharmacy and its mandated use in the prescription benefit
      plans of public and private insurance programs. METHODS: Existing published
      literature was reviewed, and interviews were conducted with Medicare-eligible
      persons aged 65 and older to identify potential areas of concern with mail order
      pharmacy services. A survey was constructed and mailed to a nationally
      representative random sample of 6,500 persons between the ages of 65 and 79 in
      July 2012. RESULTS: By the cutoff date, 669 completed surveys had been received,
      and an additional 221 had been returned as undeliverable, resulting in an overall
      response rate of 10.7%. Nearly half of respondents listed chain pharmacy as their
      primary source of prescription medications (47.7%) followed by mail service
      (34.1%), independent pharmacy (13.1%), and other (5.1%). Responses of seniors
      residing in rural zip codes compared with those in nonrural zip codes
      demonstrated significantly higher agreement with several concerns, including lost
      or stolen medications, receiving the exact medication the physician prescribed,
      and the effects of exposure to heat, cold, or moisture. Two additional concerns
      approached statistical significance: the ability to speak with a pharmacist face
      to-face and the ability to obtain medications quickly if needed. A total of 533
      (83.7%) indicated they would oppose mandated mail order in their current benefit
      plan if it would cause the local community pharmacy they rely on for immediate
      medication needs to close. The mean risk of such an eventuality that respondents
      were willing to accept was 42.2%, indicating they would oppose mandatory mail
      order if there were greater than about a 4-in-10 chance it would cause the loss
      of their local pharmacy. CONCLUSIONS: Seniors appear to be practical and
      pragmatic about the sources of their prescription medications. While most see a
      role for mail service pharmacy, they are also aware of its limitations. Many have
      needs they believe cannot be adequately met by mail service or have relationships
      with local pharmacies and pharmacists they believe are important for maintaining
      their health and well-being. As a result, seniors are relatively risk averse when
      it comes to the loss of their local community pharmacy, even if they routinely
      use mail order for most of their medications. Beyond their specific concerns,
      most seniors oppose any restrictions on their freedom to use the pharmacy of
      their choice on general principle.

PMID- 23964619
TI  - NGAL and NT-proBNP levels in diabetic patients with macroproteinuria.
AB  - BACKGROUND: In patients with heart failure plasma N-terminal pro-brain
      natriuretic peptide (NT-proBNP) levels are correlated to urine neutrophil
      gelatinase-associated lipocalin (NGAL) levels. We prospectively evaluated the
      relationship among glomerular filtration rate (eGFR), urine albumin-to-creatinine
      ratio (ACR), urine and serum NGAL and NT-proBNP levels in 20 type II diabetic
      patients with macroalbuminuria at 4-month intervals. RESULTS: Compared with 20
      age, gender-matched healthy controls, diabetic patients had higher urine and
      serum NGAL, serum NT-proBNP and lower eGFR. The eGFR of the patients at the
      baseline, the 4th and the 8th month were 29.6 +/- 12.0, 27.8 +/- 13.7 and 22.9 +/
      10.4 mL/min/1.73 m(2), respectively. No significant change in urine NGAL levels
      was detected (p > 0.05), whereas there were significant increases in NT-proBNP,
      serum NGAL and urine ACR and significant decrease in eGFR as the study progressed
      (p < 0.05). Both the baseline and the 4th month urine ACR were positively
      correlated to NT-proBNP levels measured at the same periods (r: 0.451; p: 0.046;
      r: 0.489; p: 0.029 respectively). In all measurements, urine ACR was negatively
      correlated to serum albumin levels measured at the same periods (r: -0.792; p:
      0.000; r: -0.716; p: 0.000; r: -0.531; p: 0.016 respectively). None of eGFR
      measurements was correlated with NT-proBNP (p > 0.05). Neither serum NGAL nor
      urinary NGAL levels are associated with NT-proBNP (p > 0.05). CONCLUSION: Our
      findings show an association between NT-proBNP and proteinuria in type II
      diabetic patients with macroalbuminuria but not with serum and urine NGAL.

PMID- 23964620
TI  - The pH dependence of flavivirus envelope protein structure: insights from
      molecular dynamics simulations.
AB  - The flavivirus membrane fusion is triggered by the acid pH of the endosomes after
      virus endocytosis. The proposed mechanism involves changes in the protonation
      state of conserved histidine residues of the E protein present in the viral
      surface that undergoes a series of structural rearrangements that result in the
      fusion between the endosome and viral bilayers. We studied the pH dependence of E
      protein rearrangements of dengue virus type 2, used as a model, in the pH range
      experimented by the virus along the fusion process. We employed a low
      computational cost scheme to explore the behavior of the E protein by molecular
      dynamics (MD) simulations of complete systems that include the protein, the
      solvent, and ions. The procedure alternates cyclically the update of the
      ionization states of the protein residues with common MD steps applied to the new
      ionization configuration. Important pH-dependent protein structure rearrangements
      consistent with the changes of the protonation states of conserved histidine
      residues were observed. The involvement of other conserved residues in the
      flavivirus in the rearrangements was also identified. The results show
      interesting correlations with a proposed model for the fusion mechanism, as well
      as the experimentally identified key residues, contributing to a better
      understanding of the structural changes in protein E that lead to the fusion
      process.

PMID- 23964621
TI  - Pulmonary rehabilitation and COPD: is nonlinear exercise better?

PMID- 23964622
TI  - What is the role of the non-coding regions of the CFTR gene in cystic fibrosis?

PMID- 23964623
TI  - Recent therapeutic breakthroughs in respiratory medicine.

PMID- 23964625
TI  - Efficacy and safety of high-dose ciclesonide for the treatment of severe asthma.
AB  - Asthma severity is classified according to the level of treatment required to
      control symptoms. Inhaled corticosteroids are the recommended first-line therapy
      for the treatment of persistent asthma, and when asthma remains uncontrolled, one
      option is to increase the inhaled corticosteroids dose. However, there is a
      concomitant risk of increasing local and systemic adverse events, which may
      impact patient adherence and physician prescribing practices. Ciclesonide is
      delivered as a prodrug, has high peripheral lung deposition and high protein
      binding capabilities, and is rapidly eliminated from the systemic circulation.
      This article reviews the use of high-dose ciclesonide in patients with severe
      asthma and considers whether the pharmacology of ciclesonide translates into it
      being an efficacious and well-tolerated option for patients requiring a step-up
      in their asthma treatment.

PMID- 23964626
TI  - Climate change and respiratory health: current evidence and knowledge gaps.
AB  - Climate change is a key driver of the accelerating environmental change affecting
      populations around the world. Many of these changes and our response to them can
      affect respiratory health. This is an expert opinion review of recent peer
      reviewed literature, focused on more recent medical journals and climate-health
      relevant modeling results from non-biomedical journals pertaining to climate
      interactions with air pollution. Global health impacts in low resource countries
      and migration precipitated by environmental change are addressed. The major
      findings are of respiratory health effects related to heat, air pollution, shifts
      in infectious diseases and allergens, flooding, water, food security and
      migration. The review concludes with knowledge gaps and research need that will
      support the evidence-base required to address the challenges ahead.

PMID- 23964627
TI  - The role of DNA methylation as biomarkers in the clinical management of lung
      cancer.
AB  - It is now widely accepted that cancer is caused by complex interactions between
      genetic and epigenetic factors and the environment. Only in the last 20 years,
      DNA methylation has been recognized as an epigenetic mechanism, which plays a
      major role during the development and progression of cancers. Accordingly, DNA
      methylation profiling provides a useful source for biomarkers in distinct
      clinical questions; for example, risk stratification, diagnosis, staging,
      prognosis and therapy-response prediction. In the last 10 years, not only has an
      increase in the number of papers published on this subject been seen, but also an
      impressive technological advancement allowing for the highly sensitive and
      accurate quantification of DNA methylation biomarkers in challenging sample
      types. However, the development of a suitable biomarker with appropriate assay
      technology is not trivial. This is especially true for the choice of biomarkers
      used for the management of early diagnosis of lung cancer. 

PMID- 23964628
TI  - The future of antimicrobial therapy in the era of antibiotic resistance in cystic
      fibrosis pulmonary infection.
AB  - Cystic fibrosis (CF) is characterised by chronic polymicrobial airway infection
      and inflammation, which is the major cause of morbidity and mortality. Aggressive
      use of antimicrobials has been fundamental in increasing the life expectancy of
      CF patients in recent years. However, enhanced culture and non-culture based
      detection methods have identified bacteria in the CF lung not previously isolated
      from CF patients by routine diagnostic microbiology Coupled with increasing
      antimicrobial resistance, the future of antimicrobial therapy in CF respiratory
      infection remains challenging. New strategies are needed to address these
      problems and ensure improvements in life expectancy are maintained. Potential
      future strategies include the use of new antimicrobial agents and formulations
      currently in clinical trials, alternative methods of selecting appropriate
      therapeutic regimens, determination of the pathogenicity of species newly
      associated with CF and the development of new antimicrobials and adjuvants for
      use in clinical practice.

PMID- 23964629
TI  - Advances in and the potential of vaccines for respiratory syncytial virus.
AB  - Respiratory syncytial virus (RSV) is the leading cause of serious lower
      respiratory track illness causing bronchiolitis and some mortality in infants and
      the elderly. Despite decades of research there is no licensed RSV vaccine. To
      enable the development of RSV vaccines, several major obstacles must be overcome
      including immature and waning immunity to RSV infection, the capacity of RSV to
      evade immunity and the failure of RSV infection to induce robust enduring
      immunity. Since the failure of the formalin-inactivated RSV vaccine trial, more
      cautious and deliberate progress has been made toward RSV vaccine development
      using a variety of experimental approaches. The scientific rational and the state
      of development of these approaches are reviewed in this article.

PMID- 23964630
TI  - COPD updates: what's new in pathophysiology and management?
AB  - The historic perspective that used to define chronic obstructive pulmonary
      disease has changed. As reviewed in this article, it is based on a better
      understanding of the underlying inflammatory airflow obstruction and a
      multidimensional classification, which mostly targets a subgroup called 'frequent
      exacerbators'. Clinical and radioimaging predictors are the stamina for an
      aggressive therapeutic approach. A simplified explanation of the updated Global
      Initiative for Obstructive Lung Disease guidelines will ease the burden of
      treatment selection.

PMID- 23964631
TI  - Composite-induced toxicity in human gingival and pulp fibroblast cells.
AB  - OBJECTIVE: The most important requirement for a material to be used in medical
      applications is its biocompatibility. Dental composite materials come into direct
      contact with oral tissues, especially gingival and pulpal cells. This study was
      performed to evaluate possible DNA damage in cells of human origin exposed to
      dental composites in vitro using a cytogenetic assay. MATERIALS AND METHODS: Two
      composite resins (Vertise Flow, Kalore) were tested on human gingival and pulp
      fibroblasts using the acridine orange/ethidium bromide viability staining and
      alkaline comet assay. Cultures were treated with polymerized composites in two
      different concentrations (20 mg/ml, 40 mg/ml) for 14 days. Chi-square and
      Kruskall-Wallis non-parametric test were used for the statistical analysis (p <
      0.05). RESULTS: Significant cytotoxicity was observed for 40 mg/ml of Vertise
      Flow in both cultures, while Kalore (40 mg/ml) showed cytotoxic effect only on
      human pulp fibroblasts. A significant level of DNA damage was detected for both
      materials and concentrations, in both cell cultures. CONCLUSION: If the two cell
      cultures are compared, the pulp cells were more sensitive to the cyto/genotoxic
      effects of dental composites. Based on the results, one can conclude that the use
      of tested materials may cause cellular damage in gingival and pulp fibroblasts in
      vitro.

PMID- 23964632
TI  - Can demineralized enamel surfaces be bonded safely?
AB  - OBJECTIVE: To evaluate and compare the effects of enamel demineralization,
      microabrasion therapy and casein phosphopeptide-amorphous calcium phosphate (CPP
      ACP) application on the shear bond strength (SBS) of orthodontic brackets bonded
      to enamel surfaces and enamel color. MATERIALS AND METHODS: Eighty freshly
      extracted human maxillary premolar teeth were allocated to one of the four
      groups. Brackets were bonded directly to non-demineralized enamel surfaces in
      Group I (control group), directly to the demineralized enamel surfaces in Group
      II, to demineralized enamel surfaces after CPP-ACP application in Group III and
      to demineralized enamel surfaces after microabrasion therapy in Group IV. The
      samples were stored in water for 24 h at 37 degrees C and then underwent
      thermocycling. The SBS in megapascals (MPa) was determined by a shear test with
      0.5 mm/min crosshead speed and failure types were classified with modified
      adhesive remnant index scores. The data were analyzed with one-way analyses of
      variance (ANOVA), Tukey and chi-square tests at the alpha = 0.05 level. RESULTS:
      Significant differences were found among the four groups (F = 21.57, p < 0.01).
      No significant difference was found between Group I and III (17.12 +/- 2.84 and
      15.08 +/- 3.42 MPa, respectively) or between Group III and IV (12.82 +/- 2.64
      MPa). The lowest SBS value was determined in Group II (5.88 +/- 2.12 MPa). Enamel
      demineralization, microabrasion therapy and CPP-ACP application affected enamel
      color significantly. CONCLUSION: CPP-ACP application and microabrasion therapy
      are able to increase the decreased SBS of orthodontic brackets because of enamel
      demineralization.

PMID- 23964633
TI  - The usefulness of psychometric tests in dental treatment of patients aged above
      65.
AB  - OBJECTIVE: The aim of this study was to analyze the occurrence of some
      psychological disorders in elderly people in three different social settings and
      to evaluate the impact of those problems on the adaptation of denture wearers to
      removable prostheses. MATERIALS AND METHODS: The study was conducted in three
      social settings: the geriatric clinic of a university hospital, nursing homes and
      a Third Age University school (TAU). Each group consisted of 70 randomly selected
      individuals. Of the total number of 210 subjects, 183 persons wore maxillary
      removable dentures while 150 had mandibular prostheses. Some symptoms of
      psychological disorders were diagnosed on the basis of results provided by two
      tests: GHQ and GDS. For identification of an inter-relationship between the use
      of removable dentures and the psychic status, the difficulties in adaptation to
      removable dentures were evaluated. RESULTS: Statistical analysis showed that the
      number of individuals with depressive symptoms was significantly lower in the
      group of TAU students than among the nursing home residents. No statistically
      significant difference in the occurrence of depression was found between the
      group of hospital patients and the students of TAU. A comparison of the GDS test
      results with the incidence of denture use difficulties indicated a significant
      inter-relationship. CONCLUSIONS: The GHQ and GDS tests may prove useful in the
      prosthetic treatment of those removable denture wearers who complain of oral
      discomfort without manifesting any visible causes. The proportion of elderly with
      signs of psychic disorders is significantly lower among TAU students than nursing
      home residents and hospital patients.

PMID- 23964634
TI  - Genetic variation in the promoter region of beta-defensin 1 (DEFB 1) is
      associated with high caries experience in children born with cleft lip and
      palate.
AB  - OBJECTIVE: Caries is a common disease in humans and has a multifactorial
      etiology. It has been suggested that children born with cleft lip and/or palate
      (CL/P) have a higher susceptibility to caries, but data from several independent
      cohorts does not support this assumption. Previous work from our group suggested
      DEFB 1 is associated with higher caries experience. Since it is suspected that
      children born with CL/P have the same risk factors predisposing them to caries as
      other children of the same ages, the aim was to test if DEFB 1 was associated
      with caries experience in children born with CL/P. MATERIALS AND METHODS: Sixty
      nine children born with CL/P (aged 2-12 years) were included. Twenty-seven males
      and seven females had cleft lip and palate (CLP), six males and seven females had
      cleft lip (CL) and 13 males and nine females had cleft palate (CP). Caries was
      evaluated with the DMFT/dmft index by a calibrated evaluator. Two single
      nucleotide polymorphisms in DEFB 1 were selected (rs11362 and rs1800972) based on
      being associated with higher caries experience in previous work. Genotyping were
      carried out by real-time PCR using the Taqman assay method. The statistical
      analysis was performed between 'low-to-moderate caries experience group' and the
      'high caries experience group'. Odds ratio calculations between caries experience
      and variant alleles and chi-square of Fisher exact tests at a level of
      significance of 0.05 were used. RESULTS: There was no significant difference for
      caries experience between cleft types (p = 0.551). An association was found for
      the marker rs11362 and genotype distribution (p = 0.047). When analyzed in a
      recessive model, the genotype GG in this polymorphism increased the risk for
      caries susceptibility by more than 3-times (p = 0.031; OR = 3.16; 95% CI = 0.97
      10.62). CONCLUSION: The genetic variant rs11362 in DEFB 1 influences caries
      susceptibility in CL/P children. The results support the hypothesis that
      expression of DEFB 1 in saliva may serve as a biomarker for future caries risk.

PMID- 23964635
TI  - Complex analysis of multiple single nucleotide polymorphisms as putative risk
      factors of tooth agenesis in the Hungarian population.
AB  - OBJECTIVES: The role was studied of multiple single nucleotide polymorphisms in
      tooth agenesis in the Hungarian population using a complex approach. METHODS:
      Eight SNPs, PAX9 -912 C/T, PAX9 -1031 A/G, MSX1 3755 A/G, FGFR1 T/C rs881301,
      IRF6 T/C rs764093, AXIN2-8150 A/G, AXIN2-8434 A/G and AXIN2-30224 C/T, were
      studied in 192 hypodontia and 17 oligodontia cases and in 260 healthy volunteers.
      Case-control analysis was performed to test both allelic and genotypic
      associations as well as associations at the level of haplotypes. Multivariate
      exploratory Bayesian network-based multi-level analysis of relevance (BN-BMLA) as
      well as logistic regression analysis were performed. RESULTS: Conventional
      statistics showed that PAX9 SNP -912 C/T and the MSX1 SNP changed the incidence
      of hypodontia, although after Bonferroni correction for multiple hypothesis
      testing, the effects were only borderline tendencies. Using a statistical
      analysis better suited for handling multiple hypotheses, the BN-BMLA, PAX9 SNPs
      clearly showed a synergistic effect. This was confirmed by other multivariate
      analyses and it remained significant after corrections for multiple hypothesis
      testing (p < 0.0025). The PAX9-1031-A-PAX9-912-T haplotype was the most relevant
      combination causing hypodontia. Interaction was weaker between PAX9 and MSX1,
      while other SNPs had no joint effect on hypodontia. CONCLUSION: This complex
      analysis shows the important role of PAX9 and MSX1 SNPs and of their interactions
      in tooth agenesis, while IRF6, FGFR1 and AXIN2 SNPs had no detectable role in the
      Hungarian population. These results also reveal that risk factors in hypodontia
      need to be identified in various populations, since there is considerable
      variability among them.

PMID- 23964636
TI  - Very-low-dose methadone: authors' response.

PMID- 23964638
TI  - Why are advance care planning decisions not implemented? Insights from interviews
      with Australian general practitioners.
AB  - BACKGROUND: Advance care planning (ACP) is thought to enhance patient autonomy
      and improve end-of-life care. However, there is evidence that when patients
      engage in ACP, the resultant plans are often not implemented. This has been
      attributed to either nonadherence by health professionals or inadequacies in ACP
      such as inaccessibility of the plans, plans providing ambiguous or conflicting
      instructions, and inappropriate focus on the completion of documents rather than
      communication. However, it is not known whether these postulated reasons are
      consistent with the experiences and views of health care professionals providing
      end-of-life care in the community. OBJECTIVE: Our aim was to explore the
      perspectives of general practitioners (GPs) on factors influencing the
      implementation of ACPs. METHODS: We conducted semi-structured, open-ended
      interviews of a purposive sample of 17 Australian GPs. Interview transcripts were
      analysed using constructionist grounded theory utilizing NVivo 9 software.
      RESULTS: Factors that were considered to have an important influence on the
      implementation of ACPs include: ACP factors such as form, legal standing,
      accessibility, clarity, currency, and specificity; illness factors such as
      quality of life, function, diagnosis, prognosis, and prognostic certainty; family
      factors such as family attitudes to ACP and different conceptualizations on
      whether care is provided to individuals or to a family unit; and organizational
      and care setting factors such as health care facility's attitudes and policies in
      relation to end-of-life care. CONCLUSIONS: Problems in implementation of ACPs are
      multifactorial and not necessarily due to deliberate nonadherence by health
      professionals. Potential solutions to improve the clinical impact of ACP are
      discussed.

PMID- 23964639
TI  - Radiofrequency ablation before intratumoral injection of (131)I-chTNT improves
      the tumor-to-normal tissue ratio in solid VX2 tumor.
AB  - PURPOSE: This study was aimed to investigate whether the tumor necrosis induced
      by radiofrequency ablation (RFA) can improve the ratio of tumor-to-normal tissue
      (T/NT) after intratumoral injection of (131)I-chTNT. MATERIALS AND METHOD:
      Eighteen New Zealand rabbits bearing VX2 tumor on the thigh were randomly divided
      into two treatment groups (control group: intratumoral injection of (131)I-chTNT
      alone; RFA group: RFA + intratumoral injection of (131)I-chTNT 3 days after RFA)
      and each group was further divided into three subgroups I, II, and III (1-2 cm, 2
      3 cm, and 3-4 cm in maximum diameter, respectively), by the tumor size. SPECT was
      performed to evaluate the T/NT on days 1, 8, and 15 after (131)I-chTNT injection.
      RESULTS: After treatment, all rabbits underwent the SPECT whole-body scan and the
      T/NT was analyzed. The results showed that T/NT in the RFA group (55.45+/-41.83)
      was significantly higher compared with the control group (7.23+/-5.61) (F=18.89,
      p=0.001). Meanwhile, a linear ascending trend was found for T/NT in the RFA group
      along with the follow-up time (r=0.47, p=0.01). The tumor size or the dose of
      (131)I-TNT injection had no significant effect on the variation of T/NT in both
      groups (p>0.05). CONCLUSION: RFA before intratumoral injection of (131)I-chTNT
      can dramatically improve T/NT, demonstrating the potential application of this
      combination therapy.

PMID- 23964641
TI  - Pico-force optical exchange (pico-FOX): utilizing optical forces applied to an
      orthogonal electroosmotic flow for particulate enrichment from mixed sample
      streams.
AB  - Results are reported from a combined optical force and electrokinetic
      microfluidic device that separates individual particulates from molecular
      components in a mixed sample stream. A pico-Newton optical force was applied to
      an orthogonal electroosmotic flow carrying a hydrodynamically pinched, mixed
      sample, resulting in the separation of the various particles from the sample
      stream. Different combinations of polystyrene, PMMA, and silica particles with a
      commercially available dye were utilized to test the different separation modes
      available, from purely optical force to combined optical and electrophoretic
      forces. The impact of various particle properties on particle separation and
      separation efficiency were explored, including size (2, 6, 10 MUm), refractive
      index, and electrophoretic mobility. Particle addressability was achieved by
      moving particles to different outlets on the basis of particle size, refractive
      index, and electrophoretic differences. Separations of 6 and 10 MUm polystyrene
      particles led to only 3% particle contamination in the original sample stream and
      interparticle type enrichment levels >80%. The unique addressability of three
      different particle materials (polystyrene, PMMA, and silica) of the same size (2
      MUm) led to each being separated into a unique outlet without measurable
      contamination of the other particle types using optical force and electrophoretic
      mobility. In addition to particle separation, the device was able to minimize dye
      diffusion, leading to >95% dye recovery. This combined platform would have
      applications for noninvasive sample preparation of mixed molecular/particulate
      systems for mating with traditional analytics as well as efficient removal of
      harmful, degrading components from complex mixtures. 

PMID- 23964640
TI  - Use of zebrafish apoptosis assays for preclinical drug discovery.
AB  - INTRODUCTION: Apoptosis has become an important target for drug discovery.
      Although the mouse remains the animal model of choice for the preclinical
      assessment of drug toxicity and efficacy, zebrafish are increasingly used for
      early drug studies. Here, we describe approaches for assessing drug effects on
      apoptosis in transparent zebrafish. AREAS COVERED: In this review, the authors
      discuss the drug effects on developmentally regulated apoptosis using microscopy.
      They also discuss the effects of neuroprotectants in a chemical induced disease
      model using morphometric image analysis. Finally, the authors review the effects
      of radioprotectants in irradiated whole animals using a conventional 96-well
      microplate format. EXPERT OPINION: Several challenges have limited more
      widespread use of zebrafish as the organism of choice for drug screening.
      However, zebrafish do have a number of compelling inherent advantages including:
      rapid organogenesis, transparency, statistically significant numbers of animals
      per experiment and adaptability of cell-based methods.

PMID- 23964642
TI  - Molecular speciation and mesoscale clustering in formaldehyde-methanol-water
      solutions in the presence of sodium carbonate.
AB  - Nanoporous organic gels can be synthesized from aqueous solutions of formaldehyde
      and resorcinol in the presence of basic electrolytes such as sodium carbonate. It
      is well known that formaldehyde is present in the form of methylene glycols or
      methoxy-glycols in aqueous and methanolic solutions, but influence of pH or
      electrolytes on speciation in these solutions has not been previously studied.
      Here we investigated effects of sodium carbonate on the speciation and colloidal
      scale clustering in formaldehyde-methanol-water solutions in the absence of
      resorcinol. We used (13)C NMR spectroscopy to quantitatively characterize
      molecular speciation in solutions and to estimate corresponding equilibrium
      constants for glycol dimerization and methoxylation. We found that species
      distribution is essentially independent of carbonate concentration for pH values
      between 3.4 (no carbonate) and 10.6. This was also consistent with ATR IR
      measurements of the same solutions. However, NMR spin-spin relaxation time
      measurements showed an unexpected behavior for glycols and especially for
      diglycol (but not for methanol), with relaxation times strongly decreasing with
      increasing carbonate concentration, indicating differences in local molecular
      environment of glycols. We further used dynamic light scattering to confirm the
      presence of mesoscale clustering in formaldehyde-methanol-water (for both H2O and
      D2O) solutions in the presence of sodium carbonate. We propose that the observed
      phenomena are due to glycol-rich cluster mesospecies in equilibrium bulk
      solution, together forming a thermodynamically stable mesostructured liquid
      phase. 

PMID- 23964643
TI  - Exchange-correlation interaction and AO-hybridization of alkali-metal atomic
      clusters.
AB  - The structure of alkali-metal atomic clusters is optimized with B3P86 hybrid
      functional for the highest spin state as well as with B3LYP hybrid functional for
      the lowest spin state. A dramatic change from plane to solid occurs in the
      highest spin state when the number of constituent atoms is four. The binding,
      exchange, and correlation energies are evaluated for both the highest and lowest
      spin states. Next, we explore the dependence of the exchange and correlation
      energies on the binding energy. The exchange energy contributes to the formation
      of the highest spin clusters, whereas the correlation energy contributes to the
      formation of the lowest spin clusters. The highest spin clusters are most stable
      when the exchange energy is a minimum. Then, to see why the ferromagnetic bond
      among spin-aligned identical atoms arises against Pauli exclusion principle, we
      estimate the mixing ratio of p orbitals in molecular orbitals. The s-p
      hybridization increases the binding energy in absolute value due to the extensive
      overlap of molecular orbitals and leads to generation of the highest spin
      clusters. 

PMID- 23964644
TI  - Cytotoxic psammaplysin analogues from a Suberea sp. marine sponge and the role of
      the spirooxepinisoxazoline in their activity.
AB  - Seventeen bromotyrosine-derived metabolites, including eight new compounds, were
      isolated from a Micronesian sponge of the genus Suberea. Four of the new
      compounds were psammaplysin derivatives (10-13), and the other four were
      ceratinamine derivatives (14-17). Of the compounds obtained, the psammaplysins
      exhibited cytotoxicity against human cancer cell lines (GI50 values down to 0.8
      MUM), while the ceratinamine and moloka'iamine analogues showed almost no
      activity. These results suggest that the spirooxepinisoxazoline ring system is a
      requirement for cytotoxicity and, therefore, may serve as an attractive molecular
      scaffold for the development of a potent anticancer agent.

PMID- 23964645
TI  - Interaction between amylose and tea polyphenols modulates the postprandial
      glycemic response to high-amylose maize starch.
AB  - High-amylose maize starch (HAM) is a common source material to make resistant
      starch with its high content of amylose (>70%). In the current investigation, the
      self-assembly of amylose in the presence of bioactive tea polyphenols (TPLs) and
      resulting slow digestion property of starch were explored. The experimental
      results using a mouse model showed a slow digestion property can be achieved with
      an extended and moderate glycemic response to HAM starch cocooked with TPLs.
      Further studies using a dilute aqueous amylose solution (0.1%, w/v) revealed an
      increased hydrodynamic radius of amylose molecules, indicating that TPLs could
      bridge them together, leading to increased molecular sizes. On the other hand,
      the bound TPLs interrupted the normal process of amylose recrystallizaiton
      evidenced by a decreased viscosity and storage modulus (G') of HAM (5%) gel, a
      rough surface of the cross-section of HAM film, and decreased short-range orders
      examined by Fourier transform infrared spectral analysis. Single-step degradation
      curves in the thermal gravimetric profile demonstrated the existence of a self
      assembled amylose-TPL complex, which is mainly formed through hydrogen bonding
      interaction according to the results of iodine binding and X-ray powder
      diffraction analysis. Collectively, the amylose-TPL complexation influences the
      normal self-assembling process of amylose, leading to a low-ordered crystalline
      structure, which is the basis for TPLs' function in modulating the digestion
      property of HAM starch to produce a slowly digestible starch material that is
      beneficial to postprandial glycemic control and related health effects. 

PMID- 23964646
TI  - Myeloma and pregnancy: strange bedfellows?

PMID- 23964647
TI  - Thyroid arsenic content and papillary thyroid carcinoma arising 10 years after
      oral arsenic trioxide therapy for refractory acute promyelocytic leukemia.

PMID- 23964648
TI  - Survival and prognostic factors of allogeneic hematopoietic stem cell transplant
      recipients admitted to intensive care unit.

PMID- 23964649
TI  - High serum levels of vascular endothelial growth factor-C have a positive impact
      on outcome of patients with advanced diffuse large B cell lymphoma.

PMID- 23964650
TI  - Low tumor burden is associated with early B-cell reconstitution and is a
      predictor of favorable outcome after non-myeloablative stem cell transplant for
      chronic lymphocytic leukemia.
AB  - Abstract Reconstitution, engraftment kinetics and tumor cell clearance were
      analyzed after reduced intensity conditioning hematopoietic cell transplant (RIC
      HCT) in patients with chronic lymphocytic leukemia (CLL). Patients were
      transplanted from unrelated (n = 40) or related (n = 10) donors after fludarabine
      and 2 Gy total body irradiation followed by cyclosporine and mycophenolate
      mofetil. The vast majority of patients (96%) engrafted with absolute neutrophil
      count (ANC) > 0.5 * 10(9)/L at day + 22. CLL cells decreased (median 2%, range 0
      69%) within 28 days, but disappeared by day + 180 after HCT. Donor T-cell
      chimerism increased to > 95% at day 56 and donor B-cell chimerism to 94% at day +
      360. Overall survival was 51 +/- 8%, incidence of progression 37 +/- 7% and non
      relapse related mortality (NRM) 30 +/- 7% at 4 years. The most common causes of
      NRM were graft-versus-host disease (GvHD) (14%) and sepsis (6%). Disease status
      at HCT was significantly associated with early B-cell reconstitution (p = 0.04)
      and with increased risk of relapse/progression in univariate and multivariate
      analysis (p = 0.022). Tumor cells were undetectable by day + 180, although B-cell
      reconstitution did not occur until 1.5 years after RIC-HCT. The best predictors
      for progression-free survival (PFS) and overall survival (OS) were complete
      response (CR) or first partial response (PR1) and the absence of bulky disease at
      transplant, respectively. 

PMID- 23964651
TI  - A molecular dynamics simulation-based interpretation of nuclear magnetic
      resonance multidimensional heteronuclear spectra of alpha-synuclein.dopamine
      adducts.
AB  - Multidimensional heteronuclear nuclear magnetic resonance (NMR) spectroscopy
      provides valuable structural information about adducts between naturally unfolded
      proteins and their ligands. These are often highly pharmacologically relevant.
      Unfortunately, the determination of the contributions to observed chemical shifts
      changes upon ligand binding is complicated. Here we present a tool that uses
      molecular dynamics (MD) trajectories to help interpret two-dimensional (2D) NMR
      data. We apply this tool to the naturally unfolded protein human alpha-synuclein
      interacting with dopamine, an inhibitor of fibril formation, and with its
      oxidation products in water solutions. By coupling 2D NMR experiments with MD
      simulations of the adducts in explicit water, the tool confirms with experimental
      data that the ligands bind preferentially to (125)YEMPS(129) residues in the C
      terminal region and to a few residues of the so-called NAC region consistently.
      It also suggests that the ligands might cause conformational rearrangements of
      distal residues located at the N-terminus. Hence, the performed analysis provides
      a rationale for the observed changes in chemical shifts in terms of direct
      contacts with the ligand and conformational changes in the protein.

PMID- 23964652
TI  - Identification of idiosyncratic Mycobacterium tuberculosis ribosomal protein
      subunits with implications in extraribosomal function, persistence, and drug
      resistance based on transcriptome data.
AB  - Ribosome, the protein synthesis machinery essential for all living cells,
      consists of ribosomal proteins and RNA. Extraribosomal functions have recently
      been discovered for many ribosomal proteins, acting either as individual
      regulatory proteins or as a complex with other cell components. However,
      extraribosomal functions of Mycobacterium tuberculosis ribosomal proteins have
      not been systematically addressed. To this end, M. tuberculosis ribosomal
      proteins potentially engaged in extraribosomal functions were curated by data
      mining from transcriptional profiles of M. tuberculosis exposed to diverse
      treatments. Six M. tuberculosis ribosomal proteins, namely, S3 (Rv0707, rpsC),
      L16 (Rv0708, rplP), L29 (Rv0709, rpmC), S17 (Rv0710, rpsQ), S14 (Rv2056c, rpsN2),
      and L33 (Rv2057c, rpmG1), were found to behave idiosyncratically. The function of
      these abnormal ribosomal subunits can be further explored. Special emphasis is on
      their potential value as novel targets for better antibiotics.

PMID- 23964654
TI  - Environmental health and safety considerations for nanotechnology.

PMID- 23964653
TI  - The impact of Fogarty International Center research training programs on public
      health policy and program development in Kenya and Uganda.
AB  - BACKGROUND: The Fogarty International Center (FIC) has supported research
      capacity development for over twenty years. While the mission of FIC is
      supporting and facilitating global health research conducted by U.S. and
      international investigators, building partnerships between health research
      institutions in the U.S. and abroad, and training the next generation of
      scientists to address global health needs, research capacity may impact health
      policies and programs and therefore have positive impacts on public health. We
      conducted an exploratory analysis of how FIC research training investments
      affected public health policy and program development in Kenya and Uganda.
      METHODS: We explored the long term impacts of all FIC supported research training
      programs using case studies, in Kenya and Uganda. Semi-structured in-depth
      interviews were conducted with 53 respondents and 29 focus group discussion
      participants across the two countries. Qualitative methods were supplemented by
      structured surveys of trainees and document review, including a review of
      evidence cited in policy documents. RESULTS: In the primary focal areas of FIC
      grants, notably HIV/AIDS, there were numerous examples of work conducted by
      former FIC trainees that influenced national and global policies. Facilitators
      for this influence included the strong technical skills and scientific
      reputations of the trainees, and professional networks spanning research and
      policy communities. Barriers included the fact that trainees typically had not
      received training in research communication, relatively few policy makers had
      received scientific training, and institutional constraints that undermined
      alignment of research with policy needs. CONCLUSIONS: While FIC has not focused
      its programs on the goal of policy and program influence, its investments have
      affected global and national public health policies and practice. These
      influences have occurred primarily through strengthening research skills of
      scientists and developing strong in-country networks. Further success of FIC and
      similar initiatives could be stimulated by investing more in the training of
      policy-makers, seeking to better align research with policy needs through more
      grants that are awarded directly to developing country institutions, and grants
      that better incorporate policy maker perspectives in their design and governance.
      Addressing structural constraints, for example supporting the development of
      national research agendas that inform university research, would further support
      such efforts.

PMID- 23964655
TI  - Metabolism of nanomaterials in vivo: blood circulation and organ clearance.
AB  - Before researchers apply nanomaterials (NMs) in biomedicine, they need to
      understand the blood circulation and clearance profile of these materials in
      vivo. These qualities determine the balance between nanomaterial-induced activity
      and unwanted toxicity. NMs have heterogeneous characteristics: they combine the
      bulk properties of solids with the mobility of molecules, and their highly active
      contact interfaces exhibit diverse functionalities. Any new and unexpected
      circulation features and clearance patterns are of great concern in toxicological
      studies and pharmaceutical screens. A number of studies have reported that NMs
      can enter the bloodstream directly during their application or indirectly via
      inhalation, ingestion, and dermal exposure. Due to the small size of NMs, the
      blood can then transport them throughout the circulation and to many organs where
      they can be stored. In this Account, we discuss the blood circulation and organ
      clearance patterns of NMs in the lung, liver, and kidney. The circulation of NMs
      in bloodstream is critical for delivery of inhalable NMs to extrapulmonary
      organs, the delivery of injectable NMs, the dynamics of tissue redistribution,
      and the overall targeting of drug carriers to specific cells and organs. The
      lung, liver, and kidney are the major distribution sites and target organs for
      NMs exposure, and the clearance patterns of NMs in these organs are critical for
      understanding the in vivo fate of NMs. Current studies suggest that multiple
      factors control the circulation and organ clearance of NMs. The size, shape,
      surface charge, surface functional groups, and aspect ratio of NMs as well as
      tissue microstructures strongly influence the circulation of NMs in bloodstream,
      their site-specific extravasation, and their clearance profiles within organs.
      Therefore structure design and surface modification can improve biocompatibility,
      regulate the in vivo metabolism, and reduce the toxicity of NMs. The
      biophysicochemical interactions occurring between NMs and between NMs and the
      biological milieu after the introduction of NMs into living systems may further
      influence the blood circulation and clearance profiles of NMs. These interactions
      can alter properties such as agglomeration, phase transformations, dissolution,
      degradation, protein adsorption, and surface reactivity. The physicochemical
      properties of NMs change dynamically in vivo thereby making the metabolism of NMs
      complex and difficult to predict. The development of in situ, real-time, and
      quantitative techniques, in vitro assays, and the adaptation of physiologically
      based pharmacokinetic (PBPK) and quantitative structure-activity relationship
      (QNSAR) modeling for NMs will streamline future in vivo studies.

PMID- 23964656
TI  - Treatment with heavy charged particles: systematic review of clinical data and
      current clinical (comparative) trials.
AB  - BACKGROUND: To analyze relevant data on carbon ion radiotherapy for different
      tumor indications and to review current clinical trials. MATERIAL AND METHODS:
      All published data on carbon ion radiotherapy were searched for with specific
      criteria in PUBMED. The terms for search were 'carbon ion and (radiotherapy OR
      radiation therapy) and (nirs OR chiba OR japan OR itep OR st. petersburg OR PSI
      OR dubna OR uppsala OR clatterbridge OR loma linda OR nice OR orsay OR itemba OR
      mpri OR himac OR triumf OR GSI OR HMI OR NCC OR ibmc OR pmrc OR MGH OR infn-lns
      OR shizuoka OR werc OR zibo OR md anderson OR fpti OR ncc ilsan OR boston OR
      heidelberg OR tsukuba) NOT in vitro NOT cell culture NOT review[Publication Type]
      Filters: Humans, English'. The search delivered 273 hits, of which only articles
      in English including 20 or more patients were included. Case reports were not
      considered. We subdivided into disease- and site-specific groups. RESULTS AND
      CONCLUSION: To date, several studies have been performed, however, no randomized
      trials have been conducted. Therefore, carbon ion radiotherapy must be considered
      an experimental treatment, and randomized trials comparing modern photon as well
      as proton treatments are necessary.

PMID- 23964657
TI  - Lean body mass and muscle function in head and neck cancer patients and healthy
      individuals--results from the DAHANCA 25 study.
AB  - INTRODUCTION: Loss of lean body mass is common following radiotherapy in patients
      with head and neck squamous cell carcinoma (HNSCC) and may reduce maximal muscle
      strength and functional performance. However, the associations between lean body
      mass, muscle strength and functional performance are unclear and no studies in
      HNSCC patients have compared the levels of these variables to the levels seen in
      healthy individuals. PURPOSE: The purpose of the present study was to investigate
      the associations between lean body mass, maximal muscle strength and functional
      performance in HNSCC patients and to compare the levels of these variables after
      radiotherapy and after progressive resistance training with the levels in healthy
      individuals. MATERIAL AND METHODS: Lean body mass (dual energy X-ray
      absorptiometry), maximal muscle strength (isokinetic dynamometry) and functional
      performance (10 m max gait speed, 30 s chair rise, 30 s arm curl, stair climb)
      from HNSCC patients from the DAHANCA 25 trials and data from 24 healthy
      individuals were included. RESULTS: Lean body mass and maximal muscle strength
      were significantly associated according to the gender and age-adjusted linear
      regression model (p < 0.0001). In addition, maximal muscle strength were
      associated with 30 s arm curl performance, 10 m max gait speed and 30 s chair
      rise (p < 0.0001). Multiple regression analyses showed that HNSCC patients
      expressed significant lower levels of the investigated variables after
      radiotherapy than healthy individuals (p < 0.0001), and that all differences were
      evened out after training. CONCLUSIONS: Significant associations were found
      between lean body mass, maximal muscle strength and functional performance in
      HNSCC patients. Patients expressed lower levels of these variables compared with
      healthy individuals, suggesting that lean body mass is a clinically relevant
      health factor in HNSCC patients.

PMID- 23964658
TI  - Adaptive radiotherapy in locally advanced prostate cancer using a statistical
      deformable motion model.
AB  - Daily treatment plan selection from a plan library is a major adaptive
      radiotherapy strategy to account for individual internal anatomy variations. This
      strategy depends on the initial input images being representative for the
      variations observed later in the treatment course. Focusing on locally advanced
      prostate cancer, our aim was to evaluate if residual motion of the prostate (CTV
      p) and the elective targets (CTV-sv, CTV-ln) can be prospectively accounted for
      with a statistical deformable model based on images acquired in the initial part
      of treatment. METHODS: Thirteen patients with locally advanced prostate cancer,
      each with 9-10 repeat CT scans, were included. Displacement vectors fields (DVF)
      obtained from contour-based deformable registration of delineations in the repeat
      and planning CT scans were used to create patient-specific statistical motion
      models using principal component analysis (PCA). For each patient and CTV, four
      PCA-models were created: one with all 9-10 DVF as input in addition to models
      with only four, five or six DVFs as input. Simulations of target shapes from each
      PCA-model were used to calculate iso-coverage levels, which were converted to
      contours. The levels were analyzed for sensitivity and precision. RESULTS: A
      union of the simulated shapes was able to cover at least 97%, 97% and 95% of the
      volumes of the evaluated CTV shapes for PCA-models using six, five and four DVFs
      as input, respectively. There was a decrease in sensitivity with higher iso
      coverage levels, with a sharper decline for greater target movements. Apart from
      having the steepest decline in sensitivity, CTV-sv also displayed the greatest
      influence on the number of geometries used in the PCA-model. CONCLUSIONS: PCA
      based simulations of residual motion derived from four to six DVFs as input could
      account for the majority of the target shapes present during the latter part of
      the treatment. CTV-sv displayed the greatest range in both sensitivity and
      precision.

PMID- 23964659
TI  - A study of patients not registered in the Swedish Cancer Register but reported to
      the Swedish Register of Palliative Care 2009 as deceased due to cancer.
AB  - BACKGROUND: The Swedish Cancer Register (SCR), an old and reputable health data
      register, contributes a large amount of data used in research. The quality of the
      research using SCR data depends on the completeness and validity of the register.
      In Sweden, every healthcare provider is obligated to report newly detected cases
      of cancer to the SCR regardless of the diagnostic basis. This study aimed to
      clarify whether there is an under-reporting of patients with cancer to the SCR or
      an over-reporting of cancer as cause of death to the SRPC as all patients do not
      appear in both registers. In addition, this study looked at the distribution of
      under-reporting or over-reporting related to age, sex, type of cancer, diagnostic
      basis, and department responsible for cancer diagnosis. MATERIAL AND METHODS: Of
      the 10 559 patients whose cause of death was cancer as reported to the SRPC
      (2009), 1394 patients (13.2%) were not registered in the SCR (1958-2009). Medical
      records from a representative sample of 203 patients were collected and reviewed.
      RESULTS: The medical records for 193 patients were obtained; of those, 183 (95%)
      patients should have been reported to the SCR. Among these, radiologic
      investigation was the most common basis for diagnosis and there was a significant
      over-representation of cancer of the pancreas, lung, liver, and bile ducts.
      DISCUSSION: This study cannot quantify the completeness of the SCR. The findings
      indicate that 12.5% of patients dying of cancer in palliative care are not
      reported, that specialized hospital departments diagnose the vast majority of the
      unreported patients, and that routines for how to report patients to the SCR
      based on radiological findings should be revised.

PMID- 23964660
TI  - Superconducting fiber with transition temperature up to 7.43 K in Nb2PdxS5-delta
      (0.6 < x <1).
AB  - Wiring systems powered by highly efficient superconductors have long been a dream
      of scientists, but researchers have faced practical challenges such as finding
      flexible materials. Here we report superconductivity in Nb2PdxS5-delta fibers
      with transition temperature up to 7.43 K, which have typical diameters of 0.3-3
      MUm. Superconductivity occurs in a wide range of Pd (0.6 < x <1) and S (0 < delta
      <0.61) contents, suggesting that the superconductivity in this system is very
      robust. Long fibers with suitable size provide a new route to high-power
      transmission cables and electronic devices. 

PMID- 23964662
TI  - Catalytic asymmetric construction of chiral hydropyridazines via conjugate
      addition of N-monosubstituted hydrazones to enones.
AB  - The first example of a highly enantioselective and scalable formal diaza-ene
      reaction between N-monosubstituted hydrazones and enones catalyzed by a simple
      chiral primary-second diamine salt has been developed. The catalytic process
      provides a highly practical and stereoselective synthetic method for chiral
      hydropyridazines. 

PMID- 23964661
TI  - Combined genotype and haplotype tests for region-based association studies.
AB  - BACKGROUND: Although single-SNP analysis has proven to be useful in identifying
      many disease-associated loci, region-based analysis has several advantages.
      Empirically, it has been shown that region-based genotype and haplotype
      approaches may possess much higher power than single-SNP statistical tests. Both
      high quality haplotypes and genotypes may be available for analysis given the
      development of next generation sequencing technologies and haplotype assembly
      algorithms. RESULTS: As generally it is unknown whether genotypes or haplotypes
      are more relevant for identifying an association, we propose to use both of them
      with the purpose of preserving high power under both genotype and haplotype
      disease scenarios. We suggest two approaches for a combined association test and
      investigate the performance of these two approaches based on a theoretical model,
      population genetics simulations and analysis of a real data set. CONCLUSIONS:
      Based on a theoretical model, population genetics simulations and analysis of a
      central corneal thickness (CCT) Genome Wide Association Study (GWAS) data set we
      have shown that combined genotype and haplotype approach has a high potential
      utility for applications in association studies.

PMID- 23964663
TI  - Is strain by Speckle Tracking Echocardiography dependent on user controlled
      spatial and temporal smoothing? An experimental porcine study.
AB  - BACKGROUND: Speckle Tracking Echocardiography (STE) strain analysis relies on
      both spatial and temporal smoothing. The user is often allowed to adjust these
      smoothing parameters during analysis. This experimental study investigates how
      different degrees of user controllable spatial and temporal smoothing affect
      global and regional STE strain values in recordings obtained from normal and
      ischemic myocardium. METHODS: In seven anesthetized pigs, left ventricular short-
      and long-axis B-mode cineloops were recorded before and after left anterior
      descending coronary artery occlusion. Peak- and postsystolic global STE strain in
      the radial, circumferential and longitudinal direction as well as corresponding
      regional strain in the anterior and posterior walls were measured. During post
      processing, strain values were obtained with three different degrees of both
      spatial and temporal smoothing (minimum, factory default and maximum), resulting
      in nine different combinations. RESULTS: All parameters for global and regional
      longitudinal strain were unaffected by adjustments of spatial and temporal
      smoothing in both normal and ischemic myocardium. Radial and circumferential
      strain depended on smoothing to a variable extent, radial strain being most
      affected. However, in both directions the different combinations of smoothing did
      only result in relatively small changes in the strain values. Overall, the
      maximal strain difference was found in normal myocardium for peak systolic radial
      strain of the posterior wall where strain was 22.0 +/- 2.2% with minimal spatial
      and maximal temporal smoothing and 30.9 +/- 2.6% with maximal spatial and minimal
      temporal smoothing (P < 0.05). CONCLUSIONS: Longitudinal strain was unaffected by
      different degrees of user controlled smoothing. Radial and circumferential strain
      depended on the degree of smoothing. However, in most cases these changes were
      small and would not lead to altered conclusions in a clinical setting.
      Furthermore, smoothing did not affect strain variance. For all strain parameters,
      variance remained within the corresponding interobserver variance.

PMID- 23964664
TI  - Improving the thrombin inhibitory activity of glycyrrhizin, a triterpenic
      saponin, through a molecular simplification of the carbohydrate moiety.
AB  - Glycyrrhizin, a saponin, and its aglycone glycyrrhetinic acid are natural
      products found in the Liquorice (Glycyrrhiza glabra L.) root extract. This
      saponin is known for its in vitro and in vivo thrombin inhibitory activity. The
      design and synthesis of five glycyrrhizin derivatives were carried out to improve
      the natural product activity. Compound 3b, a phthalic ester derivative of
      glycyrrhizin, presented a more pronounced thrombin inhibition (IC50  = 114.4 +/-
      1.3 MUm) than the saponin (IC50  = 235.7 +/- 1.4 MUm). Molecular docking
      simulations performed to investigate the molecular interaction between compound
      3b and the enzyme indicate that this product is, as previously determined for
      glycyrrhizin, an allosteric thrombin inhibitor. 

PMID- 23964666
TI  - Structure and dynamics of uranyl(VI) and plutonyl(VI) cations in ionic
      liquid/water mixtures via molecular dynamics simulations.
AB  - A fundamental understanding of the behavior of actinides in ionic liquids is
      required to develop advanced separation technologies. Spectroscopic measurements
      indicate a change in the coordination of uranyl in the hydrophobic ionic liquid 1
      ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][Tf2N]) as
      water is added to the system. Molecular dynamics simulations of dilute uranyl
      (UO2(2+)) and plutonyl (PuO2(2+)) ) solutions in [EMIM][Tf2N]/water mixtures have
      been performed in order to examine the molecular-level coordination and dynamics
      of the actinyl cation (AnO2(2+)) ); An = U, Pu) as the amount of water in the
      system changes. The simulations show that the actinyl cation has a strong
      preference for a first solvation shell with five oxygen atoms, although a higher
      coordination number is possible in mixtures with little or no water. Water is a
      much stronger ligand for the actinyl cation than Tf2N, with even very small
      amounts of water displacing Tf2N from the first solvation shell. When enough
      water is present, the inner coordination sphere of each actinyl cation contains
      five water molecules without any Tf2N. Water also populates the second solvation
      shell, although it does not completely displace the Tf2N. At high water
      concentrations, a significant fraction of the water is found in the bulk ionic
      liquid, where it primarily coordinates with the Tf2N anion. Potential of mean
      force simulations show that the progressive addition of up to five water
      molecules to uranyl is very favorable, with DeltaG ranging from -52.3 kJ/mol for
      the addition of the first water molecule to -37.6 kJ/mol for the addition of the
      fifth. Uranyl and plutonyl dimers formed via bridging Tf2N ligands are found in
      [EMIM][Tf2N] and in mixtures with very small amounts of water. Potential of mean
      force calculations confirm that the dimeric complexes are stable, with relative
      free energies of up to -9 kJ/mol in pure [EMIM][Tf2N]. We find that the self
      diffusion coefficients for all the components in the mixture increase as the
      water content increases, with the largest increase for water and the smallest
      increase for the ionic liquid cation and anion. The velocity autocorrelation
      functions also indicate changes in structure and dynamics as the water content
      changes.

PMID- 23964665
TI  - Acute pancreatitis associated with hemorrhagic fever with renal syndrome:
      clinical analysis of 12 cases.
AB  - BACKGROUND: Acute pancreatitis is one of the rare complications of hemorrhagic
      fever with renal syndrome (HFRS), which easy to be misdiagnosed as acute abdomen,
      usually critically ill, poor treatment effect, highly mortality. In this study,
      we retrospectively analyzed to explore the clinical characteristics, 12 cases of
      hemorrhagic fever with renal syndrome complicated with acute pancreatitis
      treatment methods and prognosis. METHODS: We conducted a retrospective study of
      HFRS in patients complicated with acute pancreatitis. 12 cases were collected
      from Ningbo first hospital between January 2001 and December 2012. Clinical
      information and laboratory parameters were obtained by reviewing literature and
      records. RESULTS: Twelve from 156 cases (7.69%) HFRS complicated with acute
      pancreatitis. Men comprised more than half (75%) of the sample population, the
      mean age was (38 +/- 19) years. Abdominal pain was the main clinical
      manifestations in all the patients, all of their serum amylase and serum lipase
      were increased, 10 patients were given the total abdomen CT examination, eight
      cases showed enlargement of the pancreas and surrounding leakage, two cases
      showed pancreatic necrosis and hemorrhage. Three cases complicated with pulmonary
      edema. In 12 cases, four of them received hemodialysis treatment, one gives
      surgical intervention. Eight cases were complete remission, three cases were
      partial remission and one case was death. CONCLUSIONS: Acute pancreatitis is one
      of rare of the serious complications of HFRS, whereas the correct diagnosis and
      clear the cause of disease is critical for improve the quality of life of
      patients and reduce the mortality, timely hemodialysis treatment is effective,
      early intervention can improve the prognosis.

PMID- 23964667
TI  - Antenatal and delivery services in Kinshasa, Democratic Republic of Congo: care
      seeking and experiences reported by women in a household-based survey.
AB  - OBJECTIVES: Increasing coverage of quality reproductive health services,
      including prevention of mother-to-child transmission services, requires
      understanding where and how these services are provided. To inform scale-up, we
      conducted a population-based survey in Kinshasa, Democratic Republic of Congo.
      METHODS: Stratified two-stage cluster sampling was used to select women >=18
      years old who had been pregnant within the prior three years. Participants were
      interviewed about their reproductive healthcare utilization and impressions of
      services received. RESULTS: We interviewed 1221 women, 98% of whom sought
      antenatal care (ANC). 78% of women began ANC after the first trimester and 22%
      reported <4 visits. Reasons for choosing an ANC facility included reputation
      (51%), friendly/accessible staff (39%), availability of comprehensive services
      (29%), medication access (26%), location (26%), and cost (21%). Most women
      reported satisfactory treatment by staff, but 47% reported that the ANC provider
      ignored their complaints, 23% had difficulty understanding responses to their
      questions, 22% wanted more time with the provider, 21% wanted more privacy, and
      12% felt uncomfortable asking questions. Only 56% reported someone talked to them
      about HIV/AIDS. Strongest predictors of seeking inadequate ANC included low
      participant and partner education and lack of certain assets. Only 32% of women
      sought postnatal care. Some results varied by health zone. CONCLUSIONS: Scaling
      up interventions to improve reproductive health services should include broad
      based health systems strengthening and promote equitable access to quality ANC,
      delivery, and postnatal services. Personal and structural-level barriers to
      seeking ANC need to be addressed, with consideration given to local contexts.

PMID- 23964668
TI  - A palmar pressure sensor for measurement of upper limb weight bearing by the
      hands during transfers by paraplegics.
AB  - Paraplegic patients have to effect transfer from one seat to another by using
      their upper limbs. In this process the hands bear almost the entire weight of the
      body in at least some phases of the transfer. It is desirable to train patients,
      especially those who are elderly and otherwise weak, to distribute their weight
      so as to avoid large forces being sustained on any one hand for an extended
      period. It is also desirable to evaluate the effectiveness of assistive devices
      like lower limb FES in sharing the load on the hand. This study presents a simple
      and versatile method of measuring palmar hand force during transfers by
      paraplegic patients. It is important that this force sensor should not interfere
      with the grasping and stabilizing properties of the hands and should permit
      normal transferring. The force sensor comprises an air-filled pouch or pillow
      that can be placed on any surface. This pneumatic sensor feels like upholstery
      padding on the surface on which it is placed. The sensor integrates the total
      pressure applied to the surface of the pouch, thereby obtaining the total force
      exerted by the palm/hand. The fabrication of the sensor is described, as well as
      the associated measurement circuit. The static calibration shows that the sensor
      is linear up to 350 N and the dynamic calibration shows that it has a bandwidth
      of 13 Hz. The sensor was fabricated using an inflated inelastic airbag attached
      to a pressure transducer. An automatic offset correction circuit in the
      preamplifier module ensures that any offset due to initial pressure or sensor
      drift is removed and the output is zero under no load condition. The key to this
      sensor arrangement is the ease of fitting it into the intended location without
      disturbing the existing arrangement for the subject's activities of daily living
      (ADL).

PMID- 23964669
TI  - Synthesis of fluorescent gold nanodot-liposome hybrids for detection of
      phospholipase C and its inhibitor.
AB  - We report the synthesis of fluorescent 11-mercaptoundecanoic acid-gold nanodot
      liposome (11-MUA-Au ND/Lip) hybrids by incorporation of gold nanoparticles (~3
      nm) and 11-MUA molecules in hydrophobic phospholipid membranes that self-assemble
      to form small unilamellar vesicles. A simple and homogeneous fluorescence assay
      for phospholipase C (PLC) was developed on the basis of the fluorescence
      quenching of 11-MUA-Au ND/Lip hybrids in aqueous solution. The fluorescence of
      the 11-MUA-Au ND/Lip hybrids is quenched by oxygen (O2) molecules in solution,
      and quenching is reduced in the presence of PLC. PLC catalyzes the hydrolysis of
      phosphatidylcholine units from Lip to yield diacylglycerol (DAG) and
      phosphocholine (PC) products, leading to the decomposition of Lip. The
      diacylglycerol further interacts with 11-MUA-Au NDs via hydrophobic interactions,
      leading to inhibition of O2 quenching. The 11-MUA-Au ND/Lip probe provides a
      limit of detection (at a signal-to-noise ratio of 3) of 0.21 nM for PLC, with
      high selectivity over other proteins, enzymes, and phospholipases. We have
      validated the practicality of using this probe for the determination of PLC
      concentrations in breast cancer cells (MCF-7 and MDA-MB-231 cell lines) and
      nontumor cells (MCF-10A cell line), revealing that the PLC activity in the first
      two is at least 1.5-fold higher than that in the third. An inhibitor assay using
      11-MUA-Au ND/Lip hybrids demonstrated that tricyclodecan-9-yl potassium xanthate
      (D609) inhibits PLC (10 nM) with an IC50 value of 3.81 +/- 0.22 MUM. This simple,
      sensitive, and selective approach holds great potential for detection of PLC in
      cancer cells and for the screening of anti-PLC drugs. 

PMID- 23964670
TI  - The influence of complementary and alternative medicine use in pregnancy on labor
      pain management choices: results from a nationally representative sample of 1,835
      women.
AB  - OBJECTIVES: This study examines involvement with a range of complementary and
      alternative medicine (CAM) during pregnancy on the use of pharmacologic (PPMT)
      and nonpharmacologic (NPMT) pain management techniques for labor and birth.
      DESIGN: Longitudinal analysis of survey data. PARTICIPANTS: A substudy (n=2445)
      of the "young" cohort of the nationally representative Australian Longitudinal
      Study on Women's Health was conducted. OUTCOME MEASURES: Use of PPMT and NPMT
      during labor and birth. RESULTS: The survey was completed by 1835 women (response
      rate, 79.2%). Most respondents used either intrapartum PPMT (81.9%) or NPMT
      (74.4%). Many (60.7%) used some form of CAM during pregnancy and also used PPMT
      during birth. More than two thirds of women (66.7%) who used NPMT used CAM during
      pregnancy. There was a general trend of increased likelihood of NPMT use by women
      who applied CAM during pregnancy. There was an inverse effect on use of epidural
      analgesia for women who consumed herbal teas during pregnancy (odds ratio, 0.60).
      CONCLUSIONS: Because of the study design, this paper does not confirm a causative
      relationship between the use of CAM during pregnancy and intrapartum pain
      management choices. It does, however, indicate that the use of CAM during
      pregnancy may not significantly affect the uptake of intrapartum PPMT, despite
      possible attempts to reduce PPMT by using NPMT. It also highlights the
      possibility of potential interactions between CAM and PPMT, given the high
      prevalence of concomitant use.

PMID- 23964672
TI  - Factors influencing the prosecution of child physical abuse cases in a Swedish
      metropolitan area.
AB  - AIM: To examine whether case characteristics of alleged child physical abuse,
      such as severity, influence criminal investigation procedures and judicial
      outcomes. METHOD: We identified all police-reported cases of nonfatal child
      physical abuse during 2006 in a Swedish metropolitan area (n = 158). Case
      characteristics were abstracted from police records. RESULTS: Over half (56%) of
      the victims were boys, and the median age group was 9-12 years. The severity of
      the alleged violence was low in 8% of cases, moderate in 51% and high in 41%.
      Suspects were interviewed in 53% of cases, with fathers more likely to be
      interviewed than mothers. Children were forensically interviewed in 52% of cases,
      with 9% physically examined by a clinician and 2.5% by a forensic specialist.
      Seven per cent of the cases were prosecuted and 1.3% resulted in summary
      punishment. We found no association between severity of alleged abuse and whether
      the suspect was interviewed, the child was forensically interviewed or physically
      examined or whether the perpetrator was prosecuted. CONCLUSION: Despite the high
      severity of alleged violence, physical examination rates were low, suggesting a
      need for criminal investigative procedures on child physical abuse to be reviewed
      in Sweden.

PMID- 23964673
TI  - Implementation of a continuing education model for nurses in Bangladesh.
AB  - An abundance of information is available to help nurses to provide evidence-based
      patient care. Professional nursing practice depends on the commitment of nurses
      to obtain new knowledge through continuing education. In many global settings,
      regulatory agencies oversee nurse registration and licensing. However, once they
      complete their formal nursing education, nurses often receive no further
      professional education. To ensure their continued competency, all nurses need to
      participate in continuing education and professional development. A partnership
      between a clinical agency and practicing nurses to implement an educational
      program allows nurses to obtain new nursing knowledge and apply it immediately in
      the clinical setting. This article discusses the need for continuing education
      for all practicing nurses and describes the implementation of a model for
      professional development of nurses in Bangladesh.

PMID- 23964674
TI  - The effect of preceptor behavior on the critical thinking skills of new graduate
      nurses in the intensive care unit.
AB  - Little research has been conducted to examine the effect of preceptor behaviors
      on the critical thinking of new graduate nurses in the intensive care unit (ICU).
      This study explored the perceptions of new graduates on the effect of preceptor
      behaviors and strategies on the development of their critical thinking skills,
      using a qualitative exploratory descriptive design. Data were collected with
      demographic surveys and semistructured interviews. Data were analyzed with a
      qualitative content analysis approach. The study showed that relationships
      between new graduates and their preceptors played a key role in the development
      of critical thinking skills in new graduate nurses, and specific practical
      implications were suggested. The study data are useful for critical care nurses,
      preceptors, nurse educators, and clinical nurse specialists. The findings
      contribute to efforts to enhance the preceptor-preceptee relationship and develop
      critical thinking skills in new graduates.

PMID- 23964675
TI  - Identifying the educational needs of emergency nurses in rural and critical
      access hospitals.
AB  - This study was conducted to determine educational needs and identify potentially
      effective educational modalities for emergency nurses working in rural and
      critical access hospitals. Although 50% of all emergency department visits to
      critical access hospitals are low-acuity cases, the 4.0% transfer rate in
      critical access hospitals is significantly higher than the 1.5% overall transfer
      rate. Nursing issues include the required breadth and depth of skills needed by
      emergency nurses in recognizing, stabilizing, and transferring patients who
      require a higher level of care. Thirty-three emergency nurses practicing in rural
      or critical access hospitals were recruited for a focus group discussion of
      educational needs, barriers, and facilitators. The discussion was transcribed,
      and constant comparison was used to identify themes. Participants identified a
      need for further education in the care of critically ill patients, those who have
      undergone bariatric surgery, geriatric patients, those with traumatic injury, and
      those with mental health issues. Themes included educational isolation and
      limited availability of resources. Developing and delivering continuing education
      to this significantly isolated practice community is vital to safe patient care.

PMID- 23964676
TI  - A chimeric p53 evades mutant p53 transdominant inhibition in cancer cells.
AB  - Because of the dominant negative effect of mutant p53, there has been limited
      success with wild-type (wt) p53 cancer gene therapy. Therefore, an alternative
      oligomerization domain for p53 was investigated to enhance the utility of p53 for
      gene therapy. The tetramerization domain of p53 was substituted with the coiled
      coil (CC) domain from Bcr (breakpoint cluster region). Our p53 variant (p53-CC)
      maintains proper nuclear localization in breast cancer cells detected via
      fluorescence microscopy and shows a similar expression profile of p53 target
      genes as wt-p53. Additionally, similar tumor suppressor activities of p53-CC and
      wt-p53 were detected by terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL), annexin-V, 7-aminoactinomycin D (7-AAD), and colony-forming
      assays. Furthermore, p53-CC was found to cause apoptosis in four different cancer
      cell lines, regardless of endogenous p53 status. Interestingly, the
      transcriptional activity of p53-CC was higher than wt-p53 in 3 different reporter
      gene assays. We hypothesized that the higher transcriptional activity of p53-CC
      over wt-p53 was due to the sequestration of wt-p53 by endogenous mutant p53 found
      in cancer cells. Co-immunoprecipitation revealed that wt-p53 does indeed interact
      with endogenous mutant p53 via its tetramerization domain, while p53-CC escapes
      this interaction. Therefore, we investigated the impact of the presence of a
      transdominant mutant p53 on tumor suppressor activities of wt-p53 and p53-CC.
      Overexpression of a potent mutant p53 along with wt-p53 or p53-CC revealed that,
      unlike wt-p53, p53-CC retains the same level of tumor suppressor activity.
      Finally, viral transduction of wt-p53 and p53-CC into a breast cancer cell line
      that harbors a tumor derived transdominant mutant p53 validated that p53-CC
      indeed evades sequestration and consequent transdominant inhibition by endogenous
      mutant p53. 

PMID- 23964677
TI  - Polyketides from the littoral plant associated fungus Pseudallescheria boydii.
AB  - Four previously unreported chemical entities, boydone A (1), boydone B (2),
      botryorhodine F (3), and botryorhodine G (4), along with five known compounds,
      fusidilactone A (5), (R)-(-)-mevalonolactone (6), (R)-(-)-lactic acid (7),
      ovalicin (8), and botryorhodine C (9), were isolated from the ethyl acetate
      extracts of the fermented broths of the fungal strain Pseudallescheria boydii
      NTOU2362. The structures of 1-9 were characterized on the basis of their
      spectroscopic data analyses. The absolute configurations of 1 and 2 were
      established by comparison with the literature and the modified Mosher's method.
      The growth inhibitory activities of 1-9 against the A549 non-small-cell lung
      cancer cell line were evaluated, and 2 and 8 exhibited moderate to potent
      bioactivities with GI50 values of 41.3 and 4.1 MUM, respectively, in comparison
      with fluorouracil (GI50 = 3.6 MUM).

PMID- 23964678
TI  - Ubbelohde effect within weak C-H...pi hydrogen bonds: the rotational spectrum of
      benzene-DCF3.
AB  - The Fourier transform microwave investigation of C6H6-DCF3 outlines a shortening
      of the distance between the two constituent molecules of about 0.0044(2) A upon H
      -> D substitution of the hydrogen atom involved in the C-H...pi hydrogen bond.
      This proves that the Ubbelohde effect takes place also within weak hydrogen
      bonding. The measure of the spectra of several (13)C isotopologues in natural
      abundance has been useful to obtain structural information. 

PMID- 23964679
TI  - Social capital, ethnic density and mental health among ethnic minority people in
      England: a mixed-methods study.
AB  - OBJECTIVES: Ethnic minority people have been suggested to be healthier when
      living in areas with a higher concentration of people from their own ethnic
      group, a so-called ethnic density effect. Explanations behind the ethnic density
      effect propose that positive health outcomes are partially attributed to the
      protective and buffering effects of increased social capital on health. In fact,
      a parallel literature has reported increased levels of social capital in areas of
      greater ethnic residential diversity, but to date, no study in England has
      explored whether increased social capital mediates the relationship between
      protective effects attributed to the residential concentration of ethnic minority
      groups and health. DESIGN: We employ a mixed-methods approach to examine the
      association between ethnicity, social capital and mental health. We analyse
      geocoded data from the 2004 Health Survey for England to examine the association
      between (1) ethnic residential concentration and health; (2) ethnic residential
      concentration and social capital; (3) social capital and health; and (4) the
      mediating effect of social capital on the association between the residential
      concentration of ethnic groups and health. To further add to our understanding of
      the processes involved, data from a qualitative study of quality older ethnic
      minority people were be used to examine accounts of the significance of place of
      residence to quality of life. RESULTS: The association between ethnic density and
      social capital varies depending on the level of measurement of social capital and
      differed across ethnic minority groups. Social capital was not found to mediate
      the association between ethnic density and health. Structural differences in the
      characteristics of the neighbourhoods where different ethnic groups reside are
      reflected in the accounts of their daily experiences, and we observed different
      narratives of neighbourhood experiences between Indian and Caribbean respondents.
      The use of mixed methods provides an important contribution to the study of
      ethnic minority people's experience of their neighbourhood, as this approach has
      allowed us to gain important insights that cannot be inferred from quantitative
      or qualitative data alone.

PMID- 23964680
TI  - Effect of fasting ramadan in diabetes control status - application of extensive
      diabetes education, serum creatinine with HbA1c statistical ANOVA and regression
      models to prevent hypoglycemia.
AB  - Ramadan fasting is an obligatory duty for Muslims. Unique physiologic and
      metabolic changes occur during fasting which requires adjustments of diabetes
      medications. Although challenging, successful fasting can be accomplished if pre
      Ramadan extensive education is provided to the patients. Current research was
      conducted to study effective Ramadan fasting with different OHAs/insulins without
      significant risk of hypoglycemia in terms of HbA1c reductions after Ramadan.
      ANOVA model was used to assess HbA1c levels among different education statuses.
      Serum creatinine was used to measure renal functions. Pre-Ramadan diabetes
      education with alteration of therapy and dosage adjustments for OHAs/insulin was
      done. Regression models for HbA1c before Ramadan with FBS before sunset were also
      synthesized as a tool to prevent hypoglycemia and successful Ramadan fasting in
      future. Out of 1046 patients, 998 patients fasted successfully without any
      episodes of hypoglycemia. 48 patients (4.58%) experienced hypoglycemia. Chi(2)
      Test for CRD/CKD with hypoglycemia was also significant (p-value < 0.001).
      Significant associations and linear regression were found for HbA1c and sunset
      FBS; RBS post-dawn with RBS mid-day and FBS at sunset. The proposed regression
      models of this study can be used as a guide in future for Ramadan diabetes
      management. Some relevant patents are also outlined in this paper. 

PMID- 23964681
TI  - Higher BMP/Smad sensitivity of tendon-derived stem cells (TDSCs) isolated from
      the collagenase-induced tendon injury model: possible mechanism for their altered
      fate in vitro.
AB  - BACKGROUND: Ectopic expression of BMP-2, BMP-4 and BMP-7 was observed in clinical
      samples of tendinopathy and collagenase-induced (CI) tendon injury rat model.
      TDSCs isolated from the CI model showed increased non-tenogenic differentiation
      potential and hence altered fate compared to the TDSCs isolated from the healthy
      animals (HT) but the mechanism is unclear. We hypothesized that sensitization of
      the BMP/Smad pathway in TDSCs (CI) might account for this difference. This study
      aimed to compare the activation state of the BMP/Smad pathway at basal level and
      upon BMP-2 stimulation in TDSCs (CI) and TDSCs (HT). METHODS: Collagenase or
      saline was injected into the patellar tendon of rats for 2 weeks. TDSCs (CI) and
      TDSCs (HT) were then isolated from the patellar tendon. The mRNA and protein
      expression of BMPs and BMP receptors in TDSCs (CI) and TDSCs (HT) were analysed.
      TDSCs from both sources were treated with rhBMP-2 and the expression of
      phosphorylated and total Smad1/5/8 was examined. RESULTS: Except for the mRNA
      levels of Bmp7 and Bmpr2, there were significant higher mRNA and protein
      expression of BMPs and BMP receptors in TDSCs (CI) compared to TDSCs (HT). TDSCs
      (CI) showed higher basal expression of total Smad1/5/8 but similar basal level of
      phosphorylated Smad1/5/8 compared to TDSCs (HT). TDSCs (CI) exhibited higher
      total and phosphorylated Smad1/5/8 upon BMP-2 stimulation. CONCLUSIONS: The
      sensitization of the BMP/Smad pathway in TDSCs (CI) might account for their
      higher non-tenogenic differentiation potential and hence altered fate. It also
      provided further support of BMPs and the BMP/Smad signaling pathway in the
      pathogenesis of tendinopathy.

PMID- 23964682
TI  - Next-generation sequencing-based mRNA and microRNA expression profiling analysis
      revealed pathways involved in the rapid growth of developing culms in Moso
      bamboo.
AB  - BACKGROUND: As one of the fastest-growing lignocellulose-abundant plants on
      Earth, bamboos can reach their final height quickly due to the expansion of
      individual internodes already present in the buds; however, the molecular
      processes underlying this phenomenon remain unclear. Moso bamboo (Phyllostachys
      heterocycla cv. Pubescens) internodes from four different developmental stages
      and three different internodes within the same stage were used in our study to
      investigate the molecular processes at the transcriptome and post-transcriptome
      level. RESULTS: Our anatomical observations indicated the development of culms
      was dominated by cell division in the initial stages and by cell elongation in
      the middle and late stages. The four major endogenous hormones appeared to
      actively promote culm development. Using next-generation sequencing-based RNA
      Seq, mRNA and microRNA expression profiling technology, we produced a
      transcriptome and post-transcriptome in possession of a large fraction of
      annotated Moso bamboo genes, and provided a molecular basis underlying the
      phenomenon of sequentially elongated internodes from the base to the top. Several
      key pathways such as environmental adaptation, signal transduction, translation,
      transport and many metabolisms were identified as involved in the rapid
      elongation of bamboo culms. CONCLUSIONS: This is the first report on the temporal
      and spatial transcriptome and gene expression and microRNA profiling in a
      developing bamboo culms. In addition to gaining more insight into the unique
      growth characteristics of bamboo, we provide a good case study to analyze gene,
      microRNA expression and profiling of non-model plant species using high
      throughput short-read sequencing. Also, we demonstrate that the integrated
      analysis of our multi-omics data, including transcriptome, post-transcriptome,
      proteome, yield more complete representations and additional biological insights,
      especially the complex dynamic processes occurring in Moso bamboo culms.

PMID- 23964683
TI  - Monitoring the kinetics of the pH-driven transition of the anthrax toxin prepore
      to the pore by biolayer interferometry and surface plasmon resonance.
AB  - Domain 2 of the anthrax protective antigen (PA) prepore heptamer unfolds and
      refolds during endosome acidification to generate an extended 100 A beta barrel
      pore that inserts into the endosomal membrane. The PA pore facilitates the pH
      dependent unfolding and translocation of bound toxin enzymic components, lethal
      factor (LF) and/or edema factor, from the endosome to the cytoplasm. We
      constructed immobilized complexes of the prepore with the PA-binding domain of LF
      (LFN) to monitor the real-time prepore to pore kinetic transition using surface
      plasmon resonance and biolayer interferometry (BLI). The kinetics of this
      transition increased as the solution pH was decreased from 7.5 to 5.0, mirroring
      acidification of the endosome. Once it had undergone the transition, the LFN-PA
      pore complex was removed from the BLI biosensor tip and deposited onto electron
      microscopy grids, where PA pore formation was confirmed by negative stain
      electron microscopy. When the soluble receptor domain (ANTRX2/CMG2) binds the
      immobilized PA prepore, the transition to the pore state was observed only after
      the pH was lowered to early (pH 5.5) or late (pH 5.0) endosomal pH conditions.
      Once the pore formed, the soluble receptor readily dissociated from the PA pore.
      Separate binding experiments with immobilized PA pores and the soluble receptor
      indicate that the receptor has a weakened propensity to bind to the transitioned
      pore. This immobilized anthrax toxin platform can be used to identify or validate
      potential antimicrobial lead compounds capable of regulating and/or inhibiting
      anthrax toxin complex formation or pore transitions. 

PMID- 23964684
TI  - Lysophosphatidylcholine-induced cytotoxicity in osteoblast-like MG-63 cells:
      involvement of transient receptor potential vanilloid 2 (TRPV2) channels.
AB  - Epidemiological studies indicate that patients suffering from atherosclerosis are
      predisposed to develop osteoporosis. Accordingly, atherogenic determinants such
      as oxidized low density lipoprotein (OxLDL) particles have been shown to alter
      bone cell functions. In this work, we investigated the cytotoxicity of
      lysophosphatidylcholine (lysoPC), a major phospholipid component generated upon
      LDL oxidation, on bone-forming MG-63 osteoblast-like cells. Cell viability was
      reduced by lysoPC in a concentration-dependent manner with a LC50 of 18.7+/-0.7
      MUM. LysoPC-induced cell death was attributed to induction of both apoptosis and
      necrosis. Since impairment of intracellular calcium homeostasis is often involved
      in mechanism of cell death, we determined the involvement of calcium in lysoPC
      induced cytotoxicity. LysoPC promoted a rapid and transient increase in
      intracellular calcium attributed to mobilization from calcium stores, followed by
      a sustained influx. Intracellular calcium mobilization was associated to
      phospholipase C (PLC)-dependent mobilization of calcium from the endoplasmic
      reticulum since inhibition of PLC or calcium depletion of reticulum endoplasmic
      with thapsigargin prevented the calcium mobilization. The calcium influx induced
      by lysoPC was abolished by inhibition of transient receptor potential vanilloid
      (TRPV) channels with ruthenium red whereas gadolinium, which inhibits canonical
      TRP (TRPC) channels, was without effect. Accordingly, expression of TRPV2 and
      TRPV4 were shown in MG-63 cells. The addition of TRPV2 inhibitor Tranilast in the
      incubation medium prevent the calcium influx triggered by lysoPC and reduced
      lysoPC-induced cytotoxicity whereas TRPV4 inhibitor RN 1734 was without effect,
      which confirms the involvement of TRPV2 activation in lysoPC-induced cell death.

PMID- 23964685
TI  - Expression, characterization and ligand specificity of lipocalin-1 interacting
      membrane receptor (LIMR).
AB  - Human lipocalin-1 interacting membrane receptor (LIMR) was the first lipocalin
      receptor to be identified, as a specific receptor for lipocalin-1 (Lcn1).
      Subsequently LIMR has been reported to interact with other ligands as well,
      notably with the bovine lipocalin beta-lactoglobulin (BLG) and with the unrelated
      secretoglobin uteroglobin (UG). To study the ligand-binding behaviour of this
      prototypic lipocalin receptor in more detail, a system was developed for the
      recombinant expression of LIMR in Drosophila Schneider 2 (S2) cells, and for the
      subsequent solubilization and purification of the protein. The receptor forms
      dimers or larger oligomers when solubilized in n-dodecyl beta-D-maltoside (DDM).
      The full-length, functional receptor was captured onto a surface plasmon
      resonance (SPR) chip via an alpha-V5 antibody, and the binding of various
      potential ligands was followed in time. In this way, LIMR was shown to be highly
      specific for Lcn1, binding the lipocalin with low micromolar to high nanomolar
      affinity. No interactions with any of the other putative ligands could be
      detected, raising doubts about the physiological relevance of the reported
      binding of BLG and UG to the receptor.

PMID- 23964686
TI  - Efficiency of the monofunctionalized C60 fullerenes as membrane targeting agents
      studied by all-atom molecular dynamics simulations.
AB  - Transmembrane translocation of C60 fullerenes functionalized by the single amino
      derivative in neutral and charged forms was studies by extensive all-atom
      molecular dynamics simulations. It is shown that these complexes exhibit very
      strong affinity to the membrane core, but their spontaneous translocation through
      the membrane is not possible at practical time scale. In contrast, free amino
      derivatives translocate through the membrane much easier than their complexes
      with fullerenes, but do not have pronounced affinity to the membrane interior.
      Our results suggest that monofunctionalized C60 could be extremely efficient
      membrane targeting agents, which facilitate accumulation of the water-soluble
      compounds in the hydrophobic core of lipid bilayer.

PMID- 23964687
TI  - Practical experiences with an extended screening strategy for genetically
      modified organisms (GMOs) in real-life samples.
AB  - Nowadays most animal feed products imported into Europe have a GMO (genetically
      modified organism) label. This means that they contain European Union (EU)
      authorized GMOs. For enforcement of these labeling requirements, it is necessary,
      with the rising number of EU-authorized GMOs, to perform an increasing number of
      analyses. In addition to this, it is necessary to test products for the potential
      presence of EU-unauthorized GMOs. Analysis for EU-authorized and -unauthorized
      GMOs in animal feed has thus become laborious and expensive. Initial screening
      steps may reduce the number of GMO identification methods that need to be
      applied, but with the increasing diversity also screening with GMO elements has
      become more complex. For the present study, the application of an informative
      detailed 24-element screening and subsequent identification strategy was applied
      in 50 animal feed samples. Almost all feed samples were labeled as containing GMO
      derived materials. The main goal of the study was therefore to investigate if a
      detailed screening strategy would reduce the number of subsequent identification
      analyses. An additional goal was to test the samples in this way for the
      potential presence of EU-unauthorized GMOs. Finally, to test the robustness of
      the approach, eight of the samples were tested in a concise interlaboratory
      study. No significant differences were found between the results of the two
      laboratories. 

PMID- 23964688
TI  - Accidental Displacement of Dental Implants Into Both Maxillary Sinuses During
      Surgery.

PMID- 23964689
TI  - Renalase is an alpha-NAD(P)H oxidase/anomerase.
AB  - Renalase is a protein hormone secreted into the blood by the kidney that is
      reported to lower blood pressure and slow heart rate. Since its discovery in
      2005, renalase has been the subject of conjecture pertaining to its catalytic
      function. While it has been widely reported that renalase is the third monoamine
      oxidase (monoamine oxidase C) that oxidizes circulating catecholamines such as
      epinephrine, there has been no convincing demonstration of this catalysis in
      vitro. Renalase is a flavoprotein whose structural topology is similar to known
      oxidases, lysine demethylases, and monooxygenases, but its active site bears no
      resemblance to that of any known flavoprotein. We have identified the catalytic
      activity of renalase as an alpha-NAD(P)H oxidase/anomerase, whereby low
      equilibrium concentrations of the alpha-anomer of NADPH and NADH initiate rapid
      reduction of the renalase flavin cofactor. The reduced cofactor then reacts with
      dioxygen to form hydrogen peroxide and releases nicotinamide dinucleotide product
      in the beta-form. These processes yield an apparent turnover number (0.5 s(-1) in
      atmospheric dioxygen) that is at least 2 orders of magnitude more rapid than any
      reported activity with catechol neurotransmitters. This highly novel activity is
      the first demonstration of a role for naturally occurring alpha-NAD(P)H anomers
      in mammalian physiology and the first report of a flavoprotein catalyzing an
      epimerization reaction. 

PMID- 23964690
TI  - Assessment of immunogenicity and safety following primary and booster
      immunisation with a CRM197 -conjugated Haemophilus influenzae type B vaccine in
      healthy Chinese infants.
AB  - BACKGROUND: Invasive meningitis and pneumonia caused by Haemophilus influenzae
      type b (Hib) is an important cause of childhood mortality in countries where Hib
      vaccination is not routine. We evaluated the non-inferiority of a licensed Hib
      vaccine, PRP-CRM(197) compared with a second licensed Hib vaccine, PRP-T,
      following the recommended Chinese immunisation schedule for infants between 6
      months and 1 year of age. METHODS: In the first study phase, 6-12 month-old
      infants received two primary doses of either PRP-CRM(197) (n = 335) or PRP-T (n =
      335) vaccine administered 1 month apart. In the second study phase 8 months
      later, the same children received a single booster dose of vaccine identical to
      that use for priming (PRP-CRM(197), n = 327; PRP-T, n = 333). Serum levels of
      anti-polyribosylribitol phosphate (PRP) antibodies were measured using enzyme
      linked immunosorbent assay (ELISA). Non-inferiority of primary and booster doses
      was assessed in terms of percentages of subjects with anti-PRP antibody levels
      associated with providing short-term (>= 0.15 MUg/ml) and long-term (>= 1.0
      MUg/ml) protection; the non-inferiority margin was set at -5%. RESULTS: PRP
      CRM(197) was demonstrated to be non-inferior to PRP-T. Anti-PRP antibodies levels
      >= 0.15 MUg/ml and >= 1.0 MUg/ml were achieved by 97% of infants in the PRP
      CRM(197) group and 98% of infants in the PRP-T group 1 month after primary
      immunisation, and by all subjects (100%) in both vaccine groups 1 month after
      booster administration. Safety profiles for both vaccines were similar; no
      serious adverse events, deaths or adverse events leading to withdrawal occurred
      during the study. CONCLUSION: PRP-CRM(197) was well-tolerated and immunologically
      non-inferior to a licensed comparator Hib vaccine in Chinese infants
      (Clinicaltrials.gov: NCT01044316 & NCT01226953).

PMID- 23964692
TI  - Synthesis, in vitro cytotoxicity and radiosensitizing activity of novel 3-[(2,4
      dinitrophenylamino)alkyl] derivatives of 5-fluorouracil.
AB  - Previously, it was reported that 3[3-(2,4-dinitrophenylamino)-propyl]-5
      fluorouracil 8c unlike its components 5-fluorouracil (5-FU) 6 and 2,4
      dinitroaniline 2 in HT-29 cells under aerobic conditions had no cytotoxicity but
      showed radiosensitizing activity. In this study several analogues of 8c differing
      in the number of linking methylene groups were prepared and tested for in vitro
      cytotoxicity and radiosensitizing activity under both aerobic and hypoxic
      conditions. Tethered compound 8a was prepared in one pot by the reaction of 5-FU
      6 with paraformaldehyde and 2,4-dinitroaniline 2 in the presence of the
      concentrated hydrochloric acid, and compounds 8b-f were prepared by the reaction
      of N-(bromoalkyl)-2,4-dinitrobenzeneamines 5b-f with 1-(t-butoxycarbonyl)-5
      fluorouracil 7 followed by hydrolysis of the protecting group. The cytotoxicity
      of the tested compounds were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT), and propidium iodide (PI)-digitonin assays and
      values of sensitization enhancement ratio (SER) as a measure of the
      radiosensitizing activity were measured from radiation survival curves in the
      absence and presence of each sensitizer for 37% survival respectively. Results
      showed that tethered compounds 8a-f induced time- and concentration-dependent
      cytotoxicity under hypoxia but had no significant effect under aerobic
      conditions. These compounds also showed selective and concentration-dependent
      radiocytotoxicity under hypoxic conditions.

PMID- 23964693
TI  - Simulations of peptide-graphene interactions in explicit water.
AB  - The interaction of graphene with biomolecules has a variety of useful
      applications. In particular, graphitic surfaces decorated with peptides are being
      considered for high performance biochemical sensors. The interaction of peptides
      with graphene can also provide insight into the binding behavior of larger
      biomolecules. In this investigation, we have computed the binding enthalpies of a
      series of GXG tripeptides with graphene using classical molecular dynamics.
      Explicit water molecules were included to capture the effect of solvent. Of the
      twenty amino acid residues examined (X in GXG), arginine, glutamine, and
      asparagine exhibit the strongest interactions with graphene. Analysis of the
      trajectories shows that the presence of graphene affects the peptide conformation
      relative to its conformation in solution. We also find that the peptides favor
      the graphene interface predominantly due to the influence of the solvent, with
      hydrophilic residues binding more strongly than hydrophobic residues. These
      results demonstrate the need to include explicit solvent atoms when modeling
      peptide-graphene systems to mimic experimental conditions. Furthermore, the
      scheme outlined herein may be widely applicable for the determination and
      validation of surface interaction parameters for a host of molecular fragments
      using a variety of techniques, ranging from coarse-grained models to quantum
      mechanical methods. 

PMID- 23964695
TI  - First total synthesis of hunanamycin A.
AB  - The first total synthesis of hunanamycin A, an antibiotic natural product with a
      pyrido[1,2,3-de]quinoxaline-2,3-dione core from a marine-derived Bacillus
      hunanensis, is disclosed. The present effort provides access to sufficient
      amounts of scarce hunanamycin A for further biological evaluation and
      confirmation of the assigned absolute configuration. In addition, four new
      analogues of the natural product are reported. 

PMID- 23964694
TI  - Guanidination of tryptic peptides without desalting for matrix-assisted laser
      desorption/ionization-time-of-flight mass spectrometry analysis.
AB  - Derivatizations that enhance mass spectral quality often require desalting, which
      presents as a bottleneck in matrix-assisted laser desorption/ionization-time-of
      flight mass spectrometry (MALDI-TOF MS)-proteomics. Guanidination, which converts
      lysine to homoarginine, an arginine analogue, can increase detection of those
      peptides 5-15-fold. Our aim was to improve guanidination by using a novel
      reagent, O-methylisourea-freebase. In a simple reaction, interfering salts were
      removed prior to guanidination. Freebase preparation took about 30 min and could
      be applied to samples all at once as opposed to desalting samples one-by-one for
      5 min each. For freebase guanidinated BSA tryptic peptides, more than 6-times the
      peptides were observed relative to tryptic peptides or those guanidinated with
      the conventional reagent, O-methylisourea hemisulfate. Peptide signals increased
      more than 10-fold relative to those from guanidination with the conventional
      reagent and were equivalent to those from conventional guanidination with
      desalting. In addition, freebase guanidination allowed for a lower limit of
      detection when combined with another derivatization, N-terminal sulfonation, as
      evidenced by tandem mass spectrometry (MS/MS) fragmentation analysis of in-gel
      digests of cytochrome c. Freebase guanidination of rat lung proteins after 2-D
      gel electrophoresis allowed for identification of all tested protein spots
      regardless of protein characteristics (MW or pI) or abundance. Co-derivatization
      with N-terminal sulfonation confirmed the identity of low-abundance proteins in 2
      D gel spots that contained more than one protein. The freebase guanidination
      reagent is simple to prepare and to implement. Desalting is not needed prior to
      MALDI-TOF MS. Freebase guanidination effectively increases the dynamic range of
      detection of lysine-containing peptides while decreasing the work needed for
      sample preparation. 

PMID- 23964696
TI  - Analysis of ECG-trunk muscle signal amplitude and heart rate relationship.
AB  - The objective of this paper is to investigate if bioelectrical signals, generated
      from trunk muscles identified in an electrocardiogram (ECG) signal presented in
      this paper as ECG-Trunk Muscles Signals amplitude (Ecg-TMSA) are correlated with
      Heart rate (HR) during different levels of physical activity and also if Ecg-TMSA
      is not influenced by mental activity. HR and Ecg-TMSA were derived from ECG in 14
      subjects when walking and jogging at different treadmill velocities from 4-10 (km
      h(-1)). The mean relationship for all 14 subjects was HR = (42.3 +/- 0.2) + (45.3
      +/- 2.8) Ecg-TMSA, r(2 )= 0.91. The result of one individual data points example
      for a 21 min experiment was (r(2 )= 0.93, p < 0.0001, n = 336). The obtained
      results show a linear relationship between Ecg-TMSA and HR. Moreover, the Ecg
      TMSA was not affected by mental activity.

PMID- 23964699
TI  - Auxiliary liver transplantation with a small deceased liver graft for cirrhotic
      liver complicated by hepatocellular carcinoma.

PMID- 23964697
TI  - Fate of TLR-1/TLR-2 agonist functionalised pDNA nanoparticles upon deposition at
      the human bronchial epithelium in vitro.
AB  - BACKGROUND: Plasmid DNA vaccination is a promising approach, but studies in non
      human primates and humans failed to achieve protective immunity. To optimise this
      technology further with focus on pulmonary administration, we developed and
      evaluated an adjuvant-equipped DNA carrier system based on the biopolymer
      chitosan. In more detail, the uptake and accompanying immune response of adjuvant
      Pam3Cys (Toll-like receptor-1/2 agonist) decorated chitosan DNA nanoparticles
      (NP) were explored by using a three-dimensional (3D) cell culture model of the
      human epithelial barrier. Pam3Cys functionalised and non-functionalised chitosan
      DNA NP were sprayed by a microsprayer onto the surface of 3D cell cultures and
      uptake of NP by epithelial and immune cells (blood monocyte-derived dendritic
      cells (MDDC) and macrophages (MDM)) was visualised by confocal laser scanning
      microscopy. In addition, immune activation by TLR pathway was monitored by
      analysis of interleukin-8 and tumor necrosis factor-alpha secretions (ELISA).
      RESULTS: At first, a high uptake rate into antigen-presenting cells (MDDC: 16
      17%; MDM: 68-75%) was obtained. Although no significant difference in uptake
      patterns was observed for Pam3Cys adjuvant functionalised and non-functionalised
      DNA NP, ELISA of interleukin-8 and tumor necrosis factor-alpha demonstrated
      clearly that Pam3Cys functionalisation elicited an overall higher immune response
      with the ranking of Pam3Cys chitosan DNA NP>chitosan DNA NP=DNA unloaded chitosan
      NP>control (culture medium). CONCLUSIONS: Chitosan-based DNA delivery enables
      uptake into abluminal MDDC, which are the most immune competent cells in the
      human lung for the induction of antigen-specific immunity. In addition, Pam3Cys
      adjuvant functionalisation of chitosan DNA NP enhances significantly an
      environment favoring recruitment of immune cells together with a Th1 associated
      (cellular) immune response due to elevated IL-8 and TNF-alpha levels. The latter
      renders this DNA delivery approach attractive for potential DNA vaccination
      against intracellular pathogens in the lung (e.g., Mycobacterium tuberculosis or
      influenza virus).

PMID- 23964700
TI  - To investigate the therapeutic potential of immunochemotherapy with cisplatin +
      78 kDa + MPL-A against Leishmania donovani in BALB/c mice.
AB  - Leishmaniasis has recently garnered attention as one of the diseases 'most
      neglected' by drug research and development, as the current therapeutic
      modalities available for the patients are ridden with unacceptable toxicity due
      to high dosage of the drug, prolonged treatment schedules, resistance and
      prohibitive costs. A successful chemotherapy requires a restoration of immune
      response; therefore, we combined Leishmania-specific 78 kDa antigen (with or
      without adjuvant MPL-A) along with a novel drug cisplatin in infected BALB/c mice
      and did its comparative analysis with chemotherapy and immunotherapy alone.
      Animals that were treated with immunochemotherapy showed maximum curative
      potential as demonstrated by a marked reduction in parasite load. Delayed-type
      hypersensitivity response to leishmanial antigens has been widely used to assess
      the level of host protection to the disease. An increased delayed-type
      hypersensitivity (DTH) response was observed in animals given immunotherapy or
      chemotherapy or immunochemotherapy; however, maximum DTH response was observed in
      animals treated with cisplatin + 78 kDa + MPL-A. These animals were also found to
      exhibit higher IgG2a levels greater cytokine (IFN-gamma and IL-2) concentrations
      suggesting the generation of a strong Th1 type of immune response which is
      responsible for resolution of the disease. 

PMID- 23964701
TI  - Evaluation of spectrum of peripheral neuropathy in predialysis patients with
      chronic kidney disease.
AB  - INTRODUCTION: Neurological complications secondary to the uremic state,
      contribute largely to the morbidity and mortality in patients with renal failure.
      The prevalence of peripheral neuropathy remains high in advanced renal
      dysfunction. MATERIALS AND METHODS: The present cross-sectional study was
      conducted on 100 adult patients of chronic kidney disease between 18 and 75 years
      of age with serum creatinine greater than 2 mg/dL. Apart from routine examination
      and baseline investigations, detailed history was elicited pertaining to
      patients' neurological symptoms, and scored according to the Neurological Symptom
      Score. Motor nerve conduction velocity was measured from right median, ulnar,
      peroneal, and tibial nerves. RESULTS: It was observed that neurological symptoms
      increased steadily with raise in serum creatinine. The mean nerve conduction
      velocities (NCVs) of right median nerve, ulnar nerve, peroneal nerve, and tibial
      nerve were 51.34 +/- 6.07, 53.04 +/- 5.91, 44.72 +/- 6.14, and 44.20 +/- 5.17,
      respectively. The NCVs of all the tested nerves decreased significantly with
      increase in serum creatinine levels (p < 0.01): 70% of the patients had uremic
      polyneuropathy; 6% had asymptomatic neuropathy, 51% had symptomatic non-disabling
      neuropathy, while disabling neuropathy was seen in 13% of the patients.
      CONCLUSION: Our data suggests that NCV testing when complimented with meticulous
      neurological assessment can provide invaluable input. These tests apart from
      helping us detect neuropathy in advanced renal dysfunction; can also detect the
      disease in largely asymptomatic patients which avoids the necessity to order for
      detailed neurophysiological investigation.

PMID- 23964703
TI  - Jet-cooled spectroscopy of the alpha-methylbenzyl radical: probing the state
      dependent effects of methyl rocking against a radical site.
AB  - The state-dependent spectroscopy of alpha-methylbenzyl radical (alpha-MeBz) has
      been studied under jet-cooled conditions. Two-color resonant two-photon
      ionization (2C-R2PI), laser-induced fluorescence, and dispersed fluorescence
      spectra were obtained for the D0-D1 electronic transition of this prototypical
      resonance-stabilized radical in which the methyl group is immediately adjacent to
      the primary radical site. Extensive Franck-Condon activity in hindered rotor
      levels was observed in the excitation spectrum, reflecting a reorientation of the
      methyl group upon electronic excitation. Dispersed fluorescence spectra from the
      set of internal rotor levels are combined with the excitation spectrum to obtain
      a global fit of the barrier heights and angular change of the methyl group in
      both D0 and D1 states. The best-fit methyl rotor potential in the ground
      electronic state (D0) is a flat-topped 3-fold potential (V3" = 151 cm(-1), V6" =
      34 cm(-1)) while the D1 state has a lower barrier (V3' = 72 cm(-1), V6' = 15 cm(
      1)) with Deltaphi = +/- pi/3, pi, consistent with a reorientation of the methyl
      group upon electronic excitation. The ground state results are compared with
      calculations carried out at the DFT B3LYP level of theory using the 6-311+G(d,p)
      basis set, and a variety of excited state calculations are carried out to compare
      against experiment. The preferred geometry of the methyl rotor in the ground
      state is anti, which switches to syn in the D1 state and in the cation. The
      calculations uncover a subtle combination of effects that contribute to the shift
      in orientation and change in barrier in the excited state relative to ground
      state. Steric interaction favors the anti conformation, while hyperconjugation is
      greater in the syn orientation. The presence of a second excited state close by
      D1 is postulated to influence the methyl rotor properties. A resonant ion-dip
      infrared (RIDIR) spectrum in the alkyl and aromatic CH stretch regions was also
      recorded, probing in a complementary way the state-dependent conformation of
      alpha-MeBz. Using a scheme in which infrared depletion occurs between excitation
      and ionization steps of the 2C-R2PI process, analogous infrared spectra in D1
      were also obtained, probing the response of the CH stretch fundamentals to
      electronic excitation. A reduced-dimension Wilson G-matrix model was implemented
      to simulate and interpret the observed infrared results. Finally, photoionization
      efficiency scans were carried out to determine the adiabatic ionization threshold
      of alpha-MeBz (IP = 6.835 +/- 0.002 eV) and provide thresholds for ionization out
      of specific internal rotor levels, which report on the methyl rotor barrier in
      the cation state.

PMID- 23964702
TI  - Preclinical evaluation of the novel monoclonal antibody H6-11 for prostate cancer
      imaging.
AB  - The biological properties of the novel monoclonal antibody (mAb) H6-11 and its
      potential utility for oncological imaging studies were evaluated using in vitro
      and in vivo assays. Immunoreactivity of H6-11 to the human prostate cancer PC-3
      cell line and solid tumor xenografts was initially demonstrated using
      immunofluorescence staining; the specificity of H6-11 for prostate cancer was
      further evaluated using a commercial array of human prostate cancer and normal
      tissue samples (n=49) in which H6-11 detected 95% of prostate adenocarcinomas.
      The Kd value of 61.7+/-30 nM was determined using 125I-labeled H6-11.
      Glycosylation analysis suggested the antigenic epitope of the glycan is an O
      linked beta-N-acetylglucoside (O-GlcNAc) group. Imaging studies of PC-3 tumor
      bearing mice were performed using both optical imaging with NIR fluorescent dye
      labeled H6-11 and microPET imaging with 89Zr-labeled H6-11. These in vivo studies
      revealed that the labeled probes accumulated in PC-3 tumors 48-72 h
      postinjection, although significant retention in liver was also observed. By 120
      h postinjection, the tumors were still evident, although the liver showed
      significant clearance. These studies suggest that the mAb H6-11 may be a useful
      tool to detect prostate cancer in vitro and in vivo.

PMID- 23964704
TI  - Asteriscane-type sesquiterpenoids from the soft coral Sinularia capillosa.
AB  - Chemical examination of the soft coral Sinularia capillosa collected from the
      South China Sea resulted in the isolation of 14 new asteriscane-type
      sesquiterpenoids, namely, capillosananes A-N (1-14), four new seco-asteriscanes,
      capillosananes O-R (15-18), and (-)-sinularone A and sinularone A. Their
      structures were determined on the basis of extensive spectroscopic analyses,
      while the absolute configurations were determined by CD and ECD calculation,
      Mosher's method, and chemical conversion. This is the first report of asteriscane
      type sesquiterpenoids from soft corals, and capillosananes Q (17) and R (18)
      represent new seco-asteriscane skeletons. Capillosanane A exhibited potent
      antifouling activity against Balanus amphitrite, with an IC50 value of 9.70 MUM,
      while capillosananes B and I and (-)-sinularone A inhibited inflammation-related
      TNF-alpha in vitro.

PMID- 23964705
TI  - The effect of topical doxycycline on corneal neovascularization.
AB  - PURPOSE: To examine the effect of topical doxycycline on human corneal
      neovascularization (CONV). MATERIALS AND METHODS: Six eyes of six patients with
      CONV received topical 1% doxycycline four times per day for three weeks and
      monitored for a total of one year. Ophthalmic evaluations included visual acuity,
      tonometry, slit-lamp examination, conjunctival swabs, quantification of CONV and
      photography. RESULTS: CONV either disappeared or was attenuated, shortened and
      less dense in five of six patients. There were no adverse effects. CONCLUSION:
      Topical doxycycline was effective in reducing CONV and healing of the ocular
      surface.

PMID- 23964706
TI  - Tumor-colonizing bacteria: a potential tumor targeting therapy.
AB  - In 1813, Vautier published his observation of tumor regression in patients who
      had suffered from gas gangrene. Since then, many publications have described the
      use of bacteria as antitumor therapy. For example, Bifidobacterium and
      Clostridium have been shown to selectively colonize tumors and to reduce tumor
      size. In addition, recent studies have focused on the use of genetic engineering
      to induce the expression of pro-drug converting enzymes, cytokines, specific
      antibodies, or suicide genes in tumor-colonizing bacteria. Moreover, some animal
      experiments have reported the treatment of tumors with engineered bacteria, and
      few side effects were observed. Therefore, based on these advances in tumor
      targeting therapy, bacteria may represent the next generation of cancer therapy.

PMID- 23964707
TI  - Reliability of spatiotemporal and kinetic gait parameters determined by a new
      instrumented treadmill system.
AB  - BACKGROUND: Despite the emerging use of treadmills integrated with pressure
      platforms as outcome tools in both clinical and research settings, published
      evidence regarding the measurement properties of these new systems is limited.
      This study evaluated the within- and between-day repeatability of spatial,
      temporal and vertical ground reaction force parameters measured by a treadmill
      system instrumented with a capacitance-based pressure platform. METHODS: Thirty
      three healthy adults (mean age, 21.5 +/- 2.8 years; height, 168.4 +/- 9.9 cm; and
      mass, 67.8 +/- 18.6 kg), walked barefoot on a treadmill system (FDM-THM-S, Zebris
      Medical GmbH) on three separate occasions. For each testing session, participants
      set their preferred pace but were blinded to treadmill speed. Spatial (foot
      rotation, step width, stride and step length), temporal (stride and step times,
      duration of stance, swing and single and double support) and peak vertical ground
      reaction force variables were collected over a 30-second capture period, equating
      to an average of 52 +/- 5 steps of steady-state walking. Testing was repeated one
      week following the initial trial and again, for a third time, 20 minutes later.
      Repeated measures ANOVAs within a generalized linear modelling framework were
      used to assess between-session differences in gait parameters. Agreement between
      gait parameters measured within the same day (session 2 and 3) and between days
      (session 1 and 2; 1 and 3) were evaluated using the 95% repeatability
      coefficient. RESULTS: There were statistically significant differences in the
      majority (14/16) of temporal, spatial and kinetic gait parameters over the three
      test sessions (P < .01). The minimum change that could be detected with 95%
      confidence ranged between 3% and 17% for temporal parameters, 14% and 33% for
      spatial parameters, and 4% and 20% for kinetic parameters between days. Within
      day repeatability was similar to that observed between days. Temporal and kinetic
      gait parameters were typically more consistent than spatial parameters. The 95%
      repeatability coefficient for vertical force peaks ranged between +/- 53 and +/-
      63 N. CONCLUSIONS: The limits of agreement in spatial parameters and ground
      reaction forces for the treadmill system encompass previously reported changes
      with neuromuscular pathology and footwear interventions. These findings provide
      clinicians and researchers with an indication of the repeatability and
      sensitivity of the Zebris treadmill system to detect changes in common
      spatiotemporal gait parameters and vertical ground reaction forces.

PMID- 23964710
TI  - Optimising the use of electronic health records to estimate the incidence of
      rheumatoid arthritis in primary care: what information is hidden in free text?
AB  - BACKGROUND: Primary care databases are a major source of data for epidemiological
      and health services research. However, most studies are based on coded
      information, ignoring information stored in free text. Using the early
      presentation of rheumatoid arthritis (RA) as an exemplar, our objective was to
      estimate the extent of data hidden within free text, using a keyword search.
      METHODS: We examined the electronic health records (EHRs) of 6,387 patients from
      the UK, aged 30 years and older, with a first coded diagnosis of RA between 2005
      and 2008. We listed indicators for RA which were present in coded format and ran
      keyword searches for similar information held in free text. The frequency of
      indicator code groups and keywords from one year before to 14 days after RA
      diagnosis were compared, and temporal relationships examined. RESULTS: One or
      more keyword for RA was found in the free text in 29% of patients prior to the RA
      diagnostic code. Keywords for inflammatory arthritis diagnoses were present for
      14% of patients whereas only 11% had a diagnostic code. Codes for synovitis were
      found in 3% of patients, but keywords were identified in an additional 17%. In
      13% of patients there was evidence of a positive rheumatoid factor test in text
      only, uncoded. No gender differences were found. Keywords generally occurred
      close in time to the coded diagnosis of rheumatoid arthritis. They were often
      found under codes indicating letters and communications. CONCLUSIONS: Potential
      cases may be missed or wrongly dated when coded data alone are used to identify
      patients with RA, as diagnostic suspicions are frequently confined to text. The
      use of EHRs to create disease registers or assess quality of care will be
      misleading if free text information is not taken into account. Methods to
      facilitate the automated processing of text need to be developed and implemented.

PMID- 23964711
TI  - Bifacial peptide nucleic acid directs cooperative folding and assembly of binary,
      ternary, and quaternary DNA complexes.
AB  - We report herein the structuring of single-stranded thymine-rich DNA sequences
      into peptide-DNA hairpin triplex structures via designed melamine-thymine
      nucleobase recognition. Melamine-displaying alpha-peptides were synthesized with
      the general form (EM*)n, where M* denotes a lysine residue side chain derivatized
      with melamine, a bifacial hydrogen bond complement for thymine. We have found
      that (EM*)n peptides, which we term bifacial peptide nucleic acid (bPNA),
      function as a noncovalent template for thymine-rich DNA tracts. Unstructured DNA
      of the general form dTnCmTn are bound to (EM*)n peptides and fold into
      cooperatively melting 1:1 bPNA-DNA hairpin complexes with dissociation constants
      in the submicromolar to low nanomolar range for n = 4-10. As the length of the
      interface (n) is decreased, the melting temperature of the bPNA-DNA complex drops
      significantly, though Kd increases are less substantial, suggestive of strong
      enthalpy-entropy compensation. This is borne out by differential scanning
      calorimetry analysis, which indicates enthalpically driven bPNA-DNA base-stacking
      that becomes markedly less exothermic as the recognition surface n decreases in
      size. The recognition interface tolerates a high number of "mismatches" and
      indicates half-site, or monofacial, recognition between melamine and thymine may
      occur if only 1 complementary nucleobase is available. Association correlates
      directly with fractional thymine content, with optimal binding when the number of
      T-T sites match the number of melamine units. Interestingly, when a DNA host has
      more T-T sites than melamine sites on bPNA, two or three bPNAs can bind to a
      single DNA, resulting in ternary and quaternary complexes that have higher
      thermal stability than the binary (1:1) bPNA-DNA complex, suggestive of
      cooperative multisite binding. In contrast, when two bPNAs of different lengths
      bind to the same DNA host, a ternary complex is formed with two melting
      transitions, corresponding to independent melting of each bPNA component from the
      complex. These data demonstrate that melamine-displaying bPNA recognize thymine
      rich DNA in predictable and multifaceted ways that allow binding affinity,
      structure stability, and stoichiometry to be tuned through simple bPNA length
      modification and matching with DNA length. Synthetic bPNA structuring elements
      may be useful tools for biotechnology. 

PMID- 23964712
TI  - A must read: clinical and professional ethics guidelines for the practice of
      thyroidology.

PMID- 23964714
TI  - Factors influencing radioiodine uptake after thyroid cancer surgery.
AB  - BACKGROUND: Total thyroidectomy followed by radioactive iodine (RAI) ablation is
      indicated for most patients with differentiated thyroid cancer. There have been
      no quantitative studies testing factors that affect uptake on post-ablation whole
      body scan. We hypothesized greater RAI uptake in patients who underwent two-stage
      total thyroidectomy (diagnostic hemithyroidectomy followed by completion
      thyroidectomy) compared to patients who underwent one-stage total thyroidectomy.
      METHODS: Medical records and whole body scan images of thyroid cancer patients
      were reviewed. Thyroid uptake as a percentage of Iodine-131 dose was calculated
      for each scan. RAI uptake was compared to procedure type, central lymph node
      dissection (CLND), extrathyroidal invasion, presence of thyroiditis and pre
      operative diagnosis. RESULTS: One hundred six patients who underwent total
      thyroidectomy and RAI ablation for differentiated thyroid cancer were included.
      There was a trend to higher RAI uptake in patients who had undergone two-stage
      thyroidectomy compared to one-stage thyroidectomy (P = 0.06). CLND was associated
      significantly lower RAI uptake (P = 0.003). On multivariate analyses, CLND was
      the only variable that retained statistical significance (P = 0.023). CLND was
      performed more often in patients undergoing one-stage thyroidectomy (P = 0.001),
      as these patients' cancer diagnosis was known prior to surgery. CONCLUSION: RAI
      uptake appeared higher in two-stage thyroidectomy than one-stage thyroidectomy.
      This difference may be attributed to CLND being performed more often in one-stage
      thyroidectomy. These results add to the discussion about the role of CLND in
      surgery for differentiated thyroid cancer.

PMID- 23964715
TI  - Controlling macromolecular topology with genetically encoded SpyTag-SpyCatcher
      chemistry.
AB  - Control of molecular topology constitutes a fundamental challenge in
      macromolecular chemistry. Here we describe the synthesis and characterization of
      artificial elastin-like proteins (ELPs) with unconventional nonlinear topologies
      including circular, tadpole, star, and H-shaped proteins using genetically
      encoded SpyTag-SpyCatcher chemistry. SpyTag is a short polypeptide that binds its
      protein partner SpyCatcher and forms isopeptide bonds under physiological
      conditions. Sequences encoding SpyTag and SpyCatcher can be strategically placed
      into ELP genes to direct post-translational topological modification in situ.
      Placement of SpyTag at the N-terminus and SpyCatcher at the C-terminus directs
      formation of circular ELPs. Induction of expression at 16  degrees C with 10 MUM
      IPTG yields 80% monomeric cyclic protein. When SpyTag is placed in the middle of
      the chain, it exhibits an even stronger tendency toward cyclization, yielding up
      to 94% monomeric tadpole proteins. Telechelic ELPs containing either SpyTag or
      SpyCatcher can be expressed, purified, and then coupled spontaneously upon mixing
      in vitro. Block proteins, 3-arm or 4-arm star proteins, and H-shaped proteins
      have been prepared, with the folded CnaB2 domain that results from the SpyTag
      SpyCatcher reaction as the molecular core or branch junction. The modular
      character of the SpyTag-SpyCatcher strategy should make it useful for preparing
      nonlinear macromolecules of diverse sequence and structure. 

PMID- 23964713
TI  - Proteome-wide detection and quantitative analysis of irreversible cysteine
      oxidation using long column UPLC-pSRM.
AB  - Reactive oxygen species (ROS) play an important role in normal biological
      functions and pathological processes. ROS is one of the driving forces for
      oxidizing proteins, especially on cysteine thiols. The labile, transient, and
      dynamic nature of oxidative modifications poses enormous technical challenges for
      both accurate modification site determination and quantitation of cysteine
      thiols. The present study describes a mass spectrometry-based approach that
      allows effective discovery and quantification of irreversible cysteine
      modifications. The utilization of a long reverse phase column provides high
      resolution chromatography to separate different forms of modified cysteine thiols
      from protein complexes or cell lysates. This Fourier transform mass spectrometry
      (FT-MS) approach enabled detection and quantitation of ataxia telangiectasia
      mutated (ATM) complex cysteine sulfoxidation states using Skyline MS1 filtering.
      When we applied the long column ultra high pressure liquid chromatography (UPLC)
      MS/MS analysis, 61 and 44 peptides from cell lysates and cells were identified
      with cysteine modifications in response to in vitro and in vivo H2O2 oxidation,
      respectively. Long column ultra high pressure liquid chromatography pseudo
      selected reaction monitoring (UPLC-pSRM) was then developed to monitor the
      oxidative level of cysteine thiols in cell lysate under varying concentrations of
      H2O2 treatment. From UPLC-pSRM analysis, the dynamic conversion of sulfinic (S
      O2H) and sulfonic acid (S-O3H) was observed within nucleoside diphosphate kinase
      (Nm23-H1) and heat shock 70 kDa protein 8 (Hsc70). These methods are suitable for
      proteome-wide studies, providing a highly sensitive, straightforward approach to
      identify proteins containing redox-sensitive cysteine thiols in biological
      systems. 

PMID- 23964716
TI  - Evaluation of Peri-Implant Bone Response in Implants Retrieved for Fracture After
      More Than 20 Years of Loading: A Case Series.
AB  - Analysis of human retrieved dental implants is a useful tool in the evaluation of
      implant success and failure. More human histological data are needed from samples
      of long-term implant service. The aim of the present case series was a
      histological and histomorphometrical evaluation of the peri-implant bone
      responses in implants retrieved for fracture after more than 20 years loading.
      The archives of the Implant Retrieval Center of the Department of Medical, Oral
      and Biotechnological Sciences of the University of Chieti-Pescara, Italy were
      searched. A total of 5 implants, retrieved after a loading period of more than 20
      years, were found: 2 had been retrieved after 20 years, 1 after 22 years, 1 after
      25 years, and 1 after 27 years. All these implants were histologically processed.
      Compact, mature bone in close contact with the implant surface was observed in
      all specimens, with no gaps or connective tissue at the interface. Bone in
      different maturation stages was found around some implants. Primarily newly
      formed bone was observed in proximity of the implant surface, while mature
      compact bone with many remodeling areas and cement lines were detected in areas
      distant from the implant. Many primary and secondary osteons were present. Bone
      to implant contact percentage varied from 37.2% to 76%. In conclusion, histology
      and histomorphometry showed that even after many years of function, all implants
      presented more than adequate bone to implant contact and they appeared to be very
      well integrated in the peri-implant bone. 

PMID- 23964717
TI  - Causes of death after surgery for colon cancer-impact of other diseases, urgent
      admittance, and gender.
AB  - OBJECTIVE. In patients with colon cancer, high age and comorbidity is common. In
      this population-based retrospective study we have investigated causes of death
      and the influence of urgent operation, and gender on survival. MATERIAL AND
      METHODS. Medical records of 413 patients with verified colon cancer were
      reviewed. The diagnosis was made during 2000-2006 and operation was performed in
      385 patients (93%). RESULTS. The overall 5-year survival after surgery was 48.3%.
      At the end of the follow-up, 128 patients (54.9%) had verified colon cancer when
      they died but 105 patients (45.1%) had no signs of colon cancer. Their 5-year
      survival was 5.5% and 41.9%, respectively (p < 0.0001). Median survival time was
      significantly shorter after urgent compared with elective admittance, 20.7 months
      versus 77.9 months, and the 5-year survival 32.4% versus 57.9% (p = 0.0001). The
      tumor stage at operation was more favorable in patients dying with no signs of
      colon cancer than in those dying with cancer regarding stage I-II (66.7% versus
      16.4%), and stage IV (1.0% versus 53.1%), but not regarding stage III (30.5%
      versus 29.7%). The overall survival in women who were operated was longer than in
      men (p = 0.045) as well as survival after elective admittance (p = 0.013).
      CONCLUSION. After a median follow-up of 56.1 months almost half of the patients
      who were dead had died from other causes than colon cancer. Ten percent of those
      patients had an incorrectly reported diagnosis of colon cancer as cause of death.
      Urgent admittance was associated with reduced survival time. The median survival
      time was longer in women than in men.

PMID- 23964718
TI  - Processing technologies and cell wall degrading enzymes to improve nutritional
      value of dried distillers grain with solubles for animal feed: an in vitro
      digestion study.
AB  - Currently, the use of maize dried distillers grain with solubles (DDGS) as
      protein source in animal feed is limited by the inferior protein quality and high
      levels of non-starch polysaccharides (NSP). Processing technologies and enzymes
      that increase NSP degradability might improve digestive utilization of DDGS,
      enhancing its potential as a source of nutrients for animals. The effects of
      various combinations of processing technologies and commercial enzyme mixtures on
      in vitro digestion and subsequent fermentation of DDGS were tested. Wet-milling,
      extrusion, and mild hydrothermal acid treatment increased in vitro protein
      digestion but had no effect on NSP. Severe hydrothermal acid treatments, however,
      effectively solubilized NSP (48-78%). Addition of enzymes did not affect NSP
      solubilization in unprocessed or processed DDGS. Although the cell wall structure
      of DDGS seems to be resistant to most milder processing technologies, in vitro
      digestion of DDGS can be effectively increased by severe hydrothermal acid
      treatments. 

PMID- 23964719
TI  - Neocortical Expansion: An Attempt toward Relating Phylogeny and Ontogeny.
AB  - The neocortex is the most characteristic feature of the human brain. On gross
      inspection, its convoluted surfaces can be seen to have overgrown and covered
      most other brain structures. In the functional sphere, it is to the neocortex
      that we attribute those behaviors assumed to be most uniquely human such as
      cognition and linguistic behavior. This essay is an attempt to understand how
      this structure expanded during the course of mammalian evolution. At present, any
      attempt must be more speculative than definitive, but it is offered in the hope
      that it will generate more discussion on a topic that is central to all
      neurobiology, as well as a number of allied disciplines. I will proceed by
      outlining current views on the evolution of the brain, briefly review the
      organization of the somatosensory cortex in several mammalian forms, and then
      discuss in some detail ontogenetic mechanisms that may have some bearing on
      neocortical phylogeny. The primary proposition put forth is that the mammalian
      neocortex is relatively unspecified by strict genetic means, and that this
      allowed the neocortex to expand and adapt to a variety of circumstances during
      the course of phylogeny. 

PMID- 23964720
TI  - Enhancement of metabolic activity in the diencephalon of monkeys performing
      working memory task: a 2-deoxyglucose study in behaving rhesus monkeys.
AB  - The 2-deoxyglucose (2-DG) method was used to study the effect of working memory
      processing on local cerebral glucose utilization (LCGU) in the diencephalon of
      the rhesus monkey. Monkeys were given [(14)C]2-DG while performing either one of
      three tasks that engaged working memory (WORK group) or one of two control tasks
      (CONT group) that used associative or non associative processes. The tasks of the
      WORK group-spatial delayed response, spatial delayed alternation, and delayed
      object alternation-are alike in that the information guiding a correct response
      changes from trial to trial and only the accurate record of the preceding
      response (or cue) is relevant for each successive trial. The CONT group, in
      contrast, performed on either a visual pattern discrimination test, in which the
      correct stimulus-response association was invariant across all trials and all
      test sessions, or on a sensorimotor task in which there was no explicit memory
      requirement. LCGU was examined in five diencephalic regions: the mammillary
      bodies, the anteroventral and anteromedial thalamus, and the parvocellular and
      magnocellular components of the mediodorsal thalamic nucleus. Comparisons across
      the two groups showed that mean LCGU in the anterior and mediodorsal thalamic
      nuclei was significantly elevated (by 12-16%) in the WORK group relative to the
      CONT group. Mean LCGU in the mammillary bodies also was higher in the WORK group
      than in the CONT group, but this difference was not significant. The present
      findings suggest that the anterior and mediodorsal thalamic nuclei represent
      diecephalic components of a neural network processing working memory. Together
      with our previous report on the enhancement of metabolic activity in the
      hippocampus and dentate gyrus, these results show that working memory has a wide
      ranging influence on cerebral metabolism and emphasize the cooperative, rather
      than dissociable, roles of the hippocampus and medial thalamus in this function. 

PMID- 23964721
TI  - Transformation from head- to shoulder-centered representation of target direction
      in arm movements.
AB  - In a previous study (Soechting and Flanders 1990a) we suggested that subjects
      used a coordinate system centered at the shoulder while pointing to targets in
      extrapersonal space. In particular, we suggested that this coordinate system was
      used to define target location in terms of its distance and the direction from
      the shoulder. In this paper we examine this suggestion in more detail. We show
      that when subjects make errors in the distance of a pointing movement, the
      computed errors in direction will depend on the origin of the coordinate system
      chosen to measure direction. From an analysis of the computed error, we estimate
      the origin of each subject's coordinate system. We artificially induced large
      errors in pointing distance by asking subjects to point half-way to a target on a
      line from the shoulder or from the head, that is, in directions from two possible
      centers. The subjects' performance on both these tasks was comparable to the
      performance of subjects asked to point directly to the target. From this finding
      we argue that there exists both a head-centered and a shoulder-centered
      representation of target location within the central nervous system. 

PMID- 23964722
TI  - Spatially Distributed Cortical Excitation Patterns of Auditory Processing during
      Contralateral and Ipsilateral Stimulation.
AB  - Utilizing the high spatial and temporal resolution of magnetoencephalography in
      conjunction with magnetic resonance images, the current study explored the
      underlying electrical patterns of cortical excitation during both contralateral
      and ipsilateral auditory stimulation. Instead of studying only the peaks of the
      N100 component of the evoked magnetic field, a 30-msec window was chosen about
      the area where the peaks occurred and the intracranial sources generating that
      component were estimated at successive 5-msec intervals. Results indicated that
      the sources for both contralateral and ipsilateral conditions were best
      represented as a continuous movement of activation in an anterior-inferior
      direction along the superior surface of the temporal lobe. Although the peak
      magnetic fields of the N100 to contralateral stimulation were of shorter latency
      and higher amplitude, the generating sources of both had very similar time
      dependent movement patterns, and comparisons of source localizations were
      dependent on the latency at which they were contrasted. 

PMID- 23964723
TI  - Genetics and epigenetics of neural function: a model.
AB  - A neural model for one- or few-trial irreversible behavior learning such as
      occurs in imprinting is introduced. It is assumed that synaptic connections in
      the relevant parts of the central nervous system are initially set up in a
      largely, but not totally random fashion, as a result, for instance, of
      differential cell-cell adhesion. The behavior to be learned is then sometimes
      exhibited, but not in a reproducible, mature way. During early neural activity,
      active postsynaptic neurons may, however, deliver a putative retrograde trophic
      factor to some of their afferent synaptic boutons. This is taken to occur
      according to a Hebb-type rule. At a later stage, only those synapses that have
      accumulated enough trophic factor are stabilized selectively. We show explicitly
      how this process may lead to a perfectly wired circuit. The calculations indicate
      that if the connections were relatively well defined from the beginning, then
      random pulses at the inputs suffice for this refinement process to take place.
      This is analogous to the maturation of neural circuits under spontaneous
      electrical activity (unsupervised learning). If the initial connections are
      "fuzzy," however, well-defined patterns of activation are needed at the inputs so
      that selective stabilization leads to a correct functional system (the model now
      behaves in an instructionist mode). Experiments suggested by the model are
      discussed, and involve the manipulation of afferent inputs, of the initial
      synapse distribution, or of the stabilization phase. 

PMID- 23964724
TI  - The bounded brain: toward quantitative neuroanatomy.
AB  - An idea that human cognitive resources are virtually without limit turns up at
      all levels of mind/brain science. This tacit unbounded-resource assumption has
      paradoxical consequences in neuroscience, particularly involving the quantitative
      incoherence of some key anatomical studies of cortical connectivity resources:
      cortical sheet area, synaptic density there, and giant axonic arborizations in
      visual cortex. This inattention to quantitative consistency checking in
      neuroanatomy appears to stem from, as a notable instance, something of the
      nonspatial character of the Cartesian concept of mind being extended to the brain
      as physical structure. 

PMID- 23964725
TI  - Gender differences in fascicular lengthening during eccentric contractions: the
      role of the patella tendon stiffness.
AB  - AIM: Elastic tendons have been suggested to attenuate fascicle lengthening during
      eccentric contractions; however, there is no in vivo evidence to support this
      hypothesis. Therefore, the aim of this study was to determine whether patella
      tendon stiffness modulates vastus lateralis (VL) fascicle lengthening during
      eccentric contractions in males and females. METHOD: Vastus lateralis and patella
      tendon properties were measured in males and females owing to previously reported
      intrinsic gender differences in tendon properties. During maximal voluntary
      eccentric knee extensions, VL fascicle lengthening and torque were recorded at
      every 10 degrees  (range of motion 20-90 degrees ). RESULTS: A significant
      correlation between maximal patella tendon stiffness and change in fascicle
      length (r=0.476, P=0.023) was observed. Similarly, there was a significant
      correlation between maximal Young's modulus and change in fascicle length
      (r=0.470, P=0.049). As expected, patella tendon stiffness and Young's modulus
      were significantly higher in males compared with females (P<0.05). Interestingly,
      change in VL fascicle length during the eccentric contractions was significantly
      greater in males compared with females (P<0.05). Based on patella tendon moment
      arm measurements, VL muscle-tendon unit elongation was estimated to be
      significantly greater in males compared with females (5.24 and 4.84 cm
      respectively). CONCLUSION: The significant difference in fascicle lengthening
      during eccentric contractions may be partly explained by the significantly higher
      patella tendon moment arm, patella tendon stiffness and Young's modulus found in
      males compared with females. The current study provides in vivo evidence to
      support the hypothesis that the tendon acts as a 'mechanical buffer' during
      eccentric contractions.

PMID- 23964726
TI  - Novel oxindole based sensitizers: synthesis and application in dye-sensitized
      solar cells.
AB  - Two novel oxindole sensitizers have been synthesized for dye-sensitized solar
      cell applications. These new dyes can provide an additional pathway to inject
      electrons into the photoanode through the partial chelation of their amide
      carbonyl groups to the TiO2 surface. Incorporation of an electron deficient
      pyridine in the acceptor of the TI125 dye was found to enhance the photovoltage
      and conversion efficiency of the cell. 

PMID- 23964728
TI  - Cat peptide antigen desensitisation for treating cat allergic
      rhinoconjunctivitis.
AB  - INTRODUCTION: Allergic rhinoconjunctivitis is an increasingly common source of
      morbidity with sensitivity to cats accounting for 10-15% of the disease burden.
      Allergy to cats is a major risk factor for the development of asthma. AREAS
      COVERED: Within the present manuscript, the current data on a novel therapeutic
      approach to treat cat allergy is reviewed. Cat Peptide Antigen Desensitisation
      (Cat-PAD) is a mixture of seven small peptides developed for the treatment of cat
      allergy. It is designed to induce immunological tolerance via binding to MHC
      class II on antigen presenting cells and interacting with regulatory T cells
      without triggering the cross-linking of IgE on mast cells and basophils. The
      peptide sequences are derived from the major cat allergen Fel d 1. The peptides
      have been selected to ensure a similar T cell response to that generated to whole
      cat dander in ex-vivo PBMC derived from cat allergic individuals. The size of the
      peptides is insufficient to induce cross-linking of IgE. Clinical data from a
      series of studies shows that Cat-PAD is able to significantly reduce allergic
      rhinoconjunctivitis symptoms after a short course of four injections over 12
      weeks, and that the treatment effect is persistent lasting 2 years after the
      start of treatment. EXPERT OPINION: Taken together Cat-PAD is a novel, well
      tolerated and promising therapeutic approach to treat cat allergic patients. Data
      from the current international Phase III study will unravel whether the concept
      is also efficient and tolerable under daily life circumstances.

PMID- 23964727
TI  - Serotonin: a novel bone mass controller may have implications for alveolar bone.
AB  - As recent studies highlight the importance of alternative mechanisms in the
      control of bone turnover, new therapeutic approaches can be envisaged for bone
      diseases and periodontitis-induced bone loss. Recently, it has been shown that
      Fluoxetine and Venlafaxine, serotonin re-uptake inhibitors commonly used as
      antidepressants, can positively or negatively affect bone loss in rat models of
      induced periodontitis. Serotonin is a neurotransmitter that can be found within
      specific nuclei of the central nervous system, but can also be produced in the
      gut and be sequestered inside platelet granules. Although it is known to be
      mainly involved in the control of mood, sleep, and intestinal physiology, recent
      evidence has pointed at far reaching effects on bone metabolism, as a mediator of
      the effects of Lrp5, a membrane receptor commonly associated with Wnt canonical
      signaling and osteoblast differentiation. Deletion of Lrp5 in mice lead to
      increased expression of Tryptophan Hydroxylase 1, the gut isoform of the enzyme
      required for serotonin synthesis, thus increasing serum levels of serotonin.
      Serotonin, in turn, could bind to HTR1B receptors on osteoblasts and stop their
      proliferation by activating PKA and CREB.Although different groups have reported
      controversial results on the existence of an Lrp5-serotonin axis and the action
      of serotonin in bone remodeling, there is convincing evidence that serotonin
      modulators such as SSRIs can affect bone turnover. Consequently, the effects of
      this drug family on periodontal physiology should be thoroughly explored. 

PMID- 23964729
TI  - Why the partition coefficient of ionic liquids is concentration-dependent.
AB  - The partition coefficient of a substance measures its solubility in octanol
      compared with water and is widely used to estimate toxicity. If a substance is
      hardly soluble in octanol, then it is practically impossible for it to enter
      (human) cells and therefore is less likely to be toxic. For novel drugs it might
      be important to penetrate the cell through the membrane or even integrate into
      it. While for most simple substances the partition coefficient is concentration
      independent at low concentrations, this is not true for a few important classes
      of complex molecules, such as ionic liquids or tensides. We present a simple
      association-dissociation model for concentration dependence of the partition
      coefficient of ionic liquids. Atomistic computer simulations serve to parametrize
      our model by calculating solvation free energies in water and octanol using
      thermodynamic integration. We demonstrate the validity of the method by
      reproducing the concentration-independent partition coefficients of small
      alcohols and the concentration-dependent partition coefficient of a commonly used
      ionic liquid, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide
      [C4MIM][NTf2]. The concentration dependence is accurately predicted in a
      concentration range of several orders of magnitude. 

PMID- 23964730
TI  - Ratiometric luminescent detection of bacterial spores with terbium chelated
      semiconducting polymer dots.
AB  - We report a ratiometric fluorescent sensor based on semiconducting polymer dots
      chelated with terbium ions to detect bacterial spores in aqueous solution.
      Fluorescent polyfluorene (PFO) dots serve as a scaffold to coordinate with
      lanthanide ions that can be sensitized by calcium dipicolinate (CaDPA), an
      important biomarker of bacterial spores. The absorption band of PFO dots extends
      to deep UV region, allowing both the reference and the sensitizer can be excited
      with a single wavelength (~275 nm). The fluorescence of PFO remains constant as a
      reference, while the Tb(3+) ions exhibit enhanced luminescence upon binding with
      DPA. The sharp fluorescence peaks of beta-phase PFO dots and the narrow-band
      emissions of Tb(3+) ions enable ratiometric and sensitive CaDPA detection with a
      linear response over nanomolar concentration and a detection limit of ~0.2 nM.
      The Pdots based sensor also show excellent selectivity to CaDPA over other
      aromatic ligands. Our results indicate that the Tb(3+) chelated Pdots sensor is
      promising for sensitive and rapid detection of bacterial spores.

PMID- 23964731
TI  - Trifluoromethylation of aryl and heteroaryl halides with fluoroform-derived
      CuCF3: scope, limitations, and mechanistic features.
AB  - Fluoroform-derived CuCF3 recently discovered in our group exhibits remarkably
      high reactivity toward aryl and heteroaryl halides, performing best in the
      absence of extra ligands. A broad variety of iodoarenes undergo smooth
      trifluoromethylation with the "ligandless" CuCF3 at 23-50  degrees C to give the
      corresponding benzotrifluorides in nearly quantitative yield. A number of much
      less reactive aromatic bromides also have been trifluoromethylated, including
      pyridine, pyrimidine, pyrazine, and thiazole derivatives as well as aryl bromides
      bearing electron-withdrawing groups and/or ortho substituents. Only the most
      electrophilic chloroarenes can be trifluoromethylated, e.g., 2-chloronicotinic
      acid. Exceptionally high chemoselectivity of the reactions (no side-formation of
      arenes, biaryls, and C2F5 derivatives) has allowed for the isolation of a large
      number of trifluoromethylated products in high yield on a gram scale (up to 20
      mmol). The CuCF3 reagent is destabilized by CuX coproduced in the reaction, the
      magnitude of the effect paralleling the Lewis acidity of CuX: CuCl > CuBr > CuI.
      While S(N)Ar and S(RN)1 mechanisms are not operational, there is a well
      pronounced ortho effect, i.e., the enhanced reactivity of ortho-substituted aryl
      halides 2-RC6H4X toward CuCF3. Intriguingly, this ortho-effect is observed for R
      = NO2, COOH, CHO, COOEt, COCH3, OCH3, and even CH3, but not for R = CN. The
      fluoroform-derived CuCF3 reagent and its reactions with haloarenes provide an
      unmatched combination of reactivity, selectivity, and low cost.

PMID- 23964732
TI  - Commentary: non-haemodynamic effects of beta-blockers in cirrhosis--more than
      meets the eye?

PMID- 23964733
TI  - Commentary: non-haemodynamic effects of beta-blockers in cirrhosis - more than
      meets the eye? Authors' reply.

PMID- 23964734
TI  - Commentary: the association between low-dose aspirin use and the incidence of
      colorectal cancer.

PMID- 23964735
TI  - Letter: East-West differences in the economic impact of functional dyspepsia.

PMID- 23964736
TI  - Letter: East-West differences in the economic impact of functional dyspepsia-
      authors' reply.

PMID- 23964737
TI  - Unraveling the phosphoproteome dynamics in mammal mitochondria from a network
      perspective.
AB  - With mitochondrion garnering more attention for its inextricable involvement in
      pathophysiological conditions, it seems imperative to understand the means by
      which the molecular pathways harbored in this organelle are regulated. Protein
      phosphorylation has been considered a central event in cellular signaling and,
      more recently, in the modulation of mitochondrial activity. Efforts have been
      made to understand the molecular mechanisms by which protein phosphorylation
      regulates mitochondrial signaling. With the advances in mass-spectrometry-based
      proteomics, there is a substantial hope and expectation in the increased
      knowledge of protein phosphorylation profile and its mode of regulation. On the
      basis of phosphorylation profiles, attempts have been made to disclose the
      kinases involved and how they control the molecular processes in mitochondria
      and, consequently, the cellular outcomes. Still, few studies have focused on
      mitochondrial phosphoproteome profiling, particularly in diseases. The present
      study reviews current data on protein phosphorylation profiling in mitochondria,
      the potential kinases involved and how pathophysiological conditions modulate the
      mitochondrial phosphoproteome. To integrate data from distinct research papers,
      we performed network analysis, with bioinformatic tools like Cytoscape, String,
      and PANTHER taking into consideration variables such as tissue specificity,
      biological processes, molecular functions, and pathophysiological conditions. For
      instance, data retrieved from these analyses evidence some homology in the
      mitochondrial phosphoproteome among liver and heart, with proteins from transport
      and oxidative phosphorylation clusters particularly susceptible to
      phosphorylation. A distinct profile was noticed for adipocytes, with proteins
      form metabolic processes, namely, triglycerides metabolism, as the main targets
      of phosphorylation. Regarding disease conditions, more phosphorylated proteins
      were observed in diabetics with some distinct phosphoproteins identified in type
      2 prediabetic states and early type 2 diabetes mellitus. Heart-failure-related
      phosphorylated proteins are in much lower amount and are mainly involved in
      transport and metabolism. Nevertheless, technical considerations related to
      mitochondria isolation and protein separation should be considered in data
      comparison among different proteomic studies. Data from the present review will
      certainly open new perspectives of protein phosphorylation in mitochondria and
      will help to envisage future studies targeting the underlying regulatory
      mechanisms. 

PMID- 23964738
TI  - Erythropoietin-mediated protection in kidney transplantation: nonerythropoietic
      EPO derivatives improve function without increasing risk of cardiovascular
      events.
AB  - The protective, nonerythropoietic effects of erythropoietin (EPO) have become
      evident in preclinical models in renal ischaemia/reperfusion injury and kidney
      transplantation. However, four recently published clinical trials using high-dose
      EPO treatment following renal transplantation did not reveal any protective
      effect for short-term renal function and even reported an increased risk of
      thrombosis. This review focusses on the current status of protective pathways
      mediated by EPO, the safety concerns using high EPO dosage and discusses the
      discrepancies between pre-clinical and clinical studies. The protective effects
      are mediated by binding of EPO to a heteromeric receptor complex consisting of
      two beta-common receptors and two EPO receptors. An important role for the
      activation of endothelial nitric oxide synthase is proposed. EPO-mediated
      cytoprotection still has enormous potential. However, only nonerythropoietic EPO
      derivatives may induce protection without increasing the risk of cardiovascular
      events. In preclinical models, nonerythropoietic EPO derivatives, such as
      carbamoylated EPO and ARA290, have been tested. These EPO derivatives improve
      renal function and do not affect erythropoiesis. Therefore, nonerythropoietic EPO
      derivatives may be able to render EPO-mediated cytoprotection useful and
      beneficial for clinical transplantation. 

PMID- 23964739
TI  - Comparison of chiropractic student scores before and after utilizing active
      learning techniques in a classroom setting.
AB  - Objective : We report the differences in final examination scores achieved by
      students at the culmination of two different teaching strategies in an
      introductory skills course. Methods : Multiple choice examination scores from six
      consecutive academic calendar sessions over 18 months (n = 503) were compared.
      Two groups were used: Cohort A (n = 290) represented students who were enrolled
      in the course 3 consecutive academic sessions before an instructional change and
      Cohort B (n = 213) included students who were enrolled in 3 consecutive academic
      sessions following the instructional change, which included a more active
      learning format. Statistical analyses used were 2-tailed independent t-test, one
      way ANOVA, Tukey's honestly significant difference (HSD), and effect size.
      Results : The 2-tailed independent t-test revealed a significant difference
      between the two groups (t = -3.71, p < .001; 95% confidence interval [CI] 1.29
      4.20). Significant difference was found in the highest performing subgroup
      compared to the lowest performing subgroup in Cohort A (F = 3.343, p = .037). For
      Cohort A subgroups 1 and 2, Tukey's HSD was p < .028. In Cohort B, no difference
      was found among subgroups (F = 1.912, p = .150, HSD p > .105). Conclusion :
      Compared to previous versions of the same course taught by the same instructor,
      the students in the new course design performed better, suggesting that using
      active learning techniques helps improve student achievement. 

PMID- 23964740
TI  - Optimization of activity, selectivity, and liability profiles in 5
      oxopyrrolopyridine DPP4 inhibitors leading to clinical candidate (Sa)-2-(3
      (aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin
      6(7H)-yl)-N,N-dimethylacetamide (BMS-767778).
AB  - Optimization of a 5-oxopyrrolopyridine series based upon structure-activity
      relationships (SARs) developed from our previous efforts on a number of related
      bicyclic series yielded compound 2s (BMS-767778) with an overall activity,
      selectivity, efficacy, PK, and developability profile suitable for progression
      into the clinic. SAR in the series and characterization of 2s are described. 

PMID- 23964741
TI  - S-nitroso-N-acetylpenicillamine (SNAP) derivatization of peptide primary amines
      to create inducible nitric oxide donor biomaterials.
AB  - An S-nitroso-N-acetylpenicillamine (SNAP) derivatization approach was used to
      modify existing free primary amines found in fibrin (a natural protein-based
      biomaterial) to generate a controlled nitric oxide (NO) releasing scaffold
      material. The duration of the derivatization reaction affects the NO release
      kinetics, the induction of controlled NO-release, hydrophobicity, swelling
      behavior, elastic moduli, rheometric character, and degradation behavior. These
      properties were quantified to determine changes in fibrin hydrogels following
      covalent attachment of SNAP. NO-releasing materials exhibited minimal
      cytotoxicity when cultured with fibroblasts or osteoblasts. Cells maintained
      viability and proliferative character on derivatized materials as demonstrated by
      Live/Dead cell staining and counting. In addition, SNAP-derivatized hydrogels
      exhibited an antimicrobial character indicative of NO-releasing materials. SNAP
      derivatization of natural polymeric biomaterials containing free primary amines
      offers a means to generate inducible NO-releasing biomaterials for use as an
      antimicrobial and regenerative support for tissue engineering. 

PMID- 23964742
TI  - X-ray structure of PTP1B in complex with a new PTP1B inhibitor.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a prototype non receptor cytoplasmic
      PTPase enzyme that has been implicated in regulation of insulin and leptin
      signaling pathways. Studies on PTP1B knockout mice and PTP1B antisense treated
      mice suggested that inhibition of PTP1B would be an effective strategy for the
      treatment of type II diabetes and obesity. Here we report the X-ray structure of
      PTP1B in complex with compound IN1834-146C (PDB ID 4I8N). The crystals belong to
      P3121 space group with cell dimensions (a = b = 87.89 A, c = 103.68 A) diffracted
      to 2.5 A. The crystal structure contained one molecule of protein in the
      asymmetric unit and was solved by molecular replacement method. The compound
      engages both catalytic site and allosteric sites of PTP1B protein. We described
      the molecular interaction of the compound with the active site residues of PTP1B
      in this crystal structure report. 

PMID- 23964743
TI  - A comparative study of unfolding of Erythrina cristagalli Lectin in chemical
      denaturant and Fluoroalcohols.
AB  - The unfolding of dimeric Erythrina cristagalli lectin (ECL) has been investigated
      and compared under different denaturing conditions in presence of chemical
      denaturant, guanidine hydrochloride (GdnHCl) and fluoroalcohols, trifluoroethanol
      (TFE) and hexafluoroisopropanol (HFIP). The GdnHCl-induced unfolding exhibits
      three-state mechanism involving structured intermediate that corresponds to
      tertiary monomer. The intermediate has been characterized by 8- anilino-1
      naphthalenesulfonate (ANS) binding, which shows ~ 30 fold increase in ANS
      fluorescence and selective chemical modification with N-bromosuccinimide when Trp
      45 and Trp 207 are possibly oxidized. The results are supported by red edge
      excitation shift (10 nm), acrylamide quenching and phosphorescence studies which
      give a (0,0) band at 412.6 nm. TFE and HFIP show differing roles and
      characteristics of ECL unfolding. In TFE, but not in HFIP, a molten globulelike
      monomeric intermediate is formed, being characterized by ANS binding and
      concentration dependent studies. TFEand HFIP-induced secondary structure changes
      of ECL, as monitored by far-UV CD, show that conversion of beta-sheet to alpha
      helix occurs at lower HFIP concentration compared to TFE perturbation, helical
      content reaching to 65 % in 80 % HFIP and 53 % in 90 % TFE. Temperature-dependent
      studies reveal that induced helix entails reduced thermal stability. FTIR results
      show partial beta-sheet to alpha-helix conversion but with quantitative yield.
      The tryptophan environment of TFE- and HFIP-induced states is dissimilar
      involving oxidation of four and three tryptophans respectively, and also differs
      from the fully unfolded state in GdnHCl when all five tryptophans undergo
      oxidation. The results offer insights into the unfolding problem of ECL. 

PMID- 23964744
TI  - Theoretical study of gas hydrate decomposition kinetics--model development.
AB  - In order to provide an estimate of the order of magnitude of intrinsic gas
      hydrate dissolution and dissociation kinetics, the "Consecutive Desorption and
      Melting Model" (CDM) is developed by applying only theoretical considerations.
      The process of gas hydrate decomposition is assumed to comprise two consecutive
      and repetitive quasi chemical reaction steps. These are desorption of the guest
      molecule followed by local solid body melting. The individual kinetic steps are
      modeled according to the "Statistical Rate Theory of Interfacial Transport" and
      the Wilson-Frenkel approach. All missing required model parameters are directly
      linked to geometric considerations and a thermodynamic gas hydrate equilibrium
      model. 

PMID- 23964745
TI  - The relationship between children kidney diseases and adult ESRD--an
      epidemiological investigation of 700 cases.
AB  - BACKGROUND: We planned an epidemic investigation of 700 cases who suffered from
      chronic renal failure (CRF) to search for the evidence to demonstrate the
      relationship between children kidney diseases and adult CRF. METHODS: Seven
      hundred patients from four hospitals in Chengdu, China, were investigated face-to
      face to complete a questionnaire referring to the information of diagnoses,
      treatment, history and so on. These enumeration count data were analyzed by
      statistical description. RESULTS: In 700 patients, there were 402 male and 298
      female including 21 children and 679 adults. In the disease spectrum, the unclear
      accounted for 36.3% of totality. Chronic glomerulonephritis made the top
      proportion (14.4%) in primary kidney diseases. Diabetic nephropathy (15.3%),
      hypertensive nephropathy (10.1%), and gouty nephropathy (6%) made the primary
      proportion in secondary kidney diseases. In 21 children, chronic
      glomerulonephritis had the highest proportion of 52.4%, followed by nephrotic
      syndrome (19%), Henoch-Schonlein purpura (9.5%), and urinary tract obstruction
      (4.8%). Thirty-eight cases developed into kidney diseases during childhood
      including 21 children mentioned above, in which 17 cases presented CRF in the
      adult stage. The primary renal diseases are chronic glomerulonephritis (60.5%),
      purpura nephritis (18.4%), nephrotic syndrome (10.5%), urinary tract obstruction
      (2.6%), and the unclear (7.9%). CONCLUSION: The survey showed that there were a
      high proportion of patients whose causes were unknown, to which attention should
      be paid. Chronic glomerulonephritis remained the main cause of CRF no matter
      whether in children or in adults. Purpura during childhood, used to be thought as
      self-limited, might eventually develop into CRF in adulthood, which caught our
      eyes.

PMID- 23964746
TI  - Ingestion of low dose pyroglutamyl leucine improves dextran sulfate sodium
      induced colitis and intestinal microbiota in mice.
AB  - Inflammatory bowel diseases (IBD) are based on chronic inflammation in the
      gastrointestinal tract. We previously found anti-inflammatory peptide pyroGlu-Leu
      in the enzymatic hydrolysate of wheat gluten. The objective of present study is
      to elucidate improvement of colitis by oral administration of pyroGlu-Leu in an
      animal model. Acute colitis was induced by dextran sulfate sodium (DSS), and
      various concentrations of pyroGlu-Leu were administrated by oral gavage for 7
      days. A dose of 0.1 mg/kg body weight/day showed the most significant
      improvement. The pyroGlu-Leu concentration was significantly increased 24 h after
      oral administration both in the small intestine and the colon compared with the
      baseline. It was 20-fold higher in the small intestine than the colon.
      Administration of pyroGlu-Leu normalized population of Bacteroidetes and
      Firmicutes in the colon. These results indicate that pyroGlu-Leu has a potential
      therapeutic effect against IBD at a practical dose. 

PMID- 23964747
TI  - Bioanalysis for biocatalysis: multiplexed capillary electrophoresis-mass
      spectrometry assay for aminotransferase substrate discovery and specificity
      profiling.
AB  - In this work, we introduce an entirely automated enzyme assay based on capillary
      electrophoresis coupled to electrospray ionization mass spectrometry termed
      MINISEP-MS for multiple interfluent nanoinjections-incubation-separation-enzyme
      profiling using mass spectrometry. MINISEP-MS requires only nanoliters of reagent
      solutions and uses the separation capillary as a microreactor, allowing multiple
      substrates to be assayed simultaneously. The method can be used to rapidly
      profile the substrate specificity of any enzyme and to measure steady-state
      kinetics in an automated fashion. We used the MINISEP-MS assay to profile the
      substrate specificity of three aminotransferases (E. coli aspartate
      aminotransferase, E. coli branched-chain amino acid aminotransferase, and
      Bacillus sp. YM-1 D-amino acid aminotransferase) for 33 potential amino acid
      substrates and to measure steady-state kinetics. Using MINISEP-MS, we were able
      to recapitulate the known substrate specificities and to discover new amino acid
      substrates for these industrially relevant enzymes. Additionally, we were able to
      measure the apparent K(M) and k(cat) parameters for amino acid donor substrates
      of these aminotransferases. Because of its many advantages, the MINISEP-MS assay
      has the potential of becoming a useful tool for researchers aiming to identify or
      create novel enzymes for specific biocatalytic applications.

PMID- 23964748
TI  - Characterization of carbapenem nonsusceptible Pseudomonas aeruginosa in Denmark:
      a nationwide, prospective study.
AB  - From January 1st 2011 through June 30th 2011, 116 nonreplicate, noncystic
      fibrosis-related Pseudomonas aeruginosa isolates with reduced carbapenem
      susceptibility were collected from 12 out of 13 Danish departments of clinical
      microbiology. The presence of acquired beta-lactamases was assessed with
      combination tablet-diffusion methodology and polymerase chain reaction. In
      addition, antimicrobial susceptibility testing, an efflux pump inhibitor assay,
      and pulsed-field gel electrophoresis (PFGE) were performed. Isolates producing
      acquired beta-lactamases were further investigated by serotyping and multi locus
      sequence typing. Eight isolates produced the metallo-beta-lactamase (MBL) VIM-2,
      and one isolate produced OXA-10 and VEB-1-like extended-spectrum beta-lactamase
      (ESBL). Phenotypic indications of derepressed AmpC and efflux pump were seen in
      56 and 43 isolates, respectively. Overall, the results indicate that mutational
      factors related to permeability--often combined with derepressed, chromosomal
      AmpC--is the main factor behind carbapenem nonsusceptibility in Danish P.
      aeruginosa isolates. The ESBL producer and all the VIM producers belonged to
      international clones. PFGE revealed that most of the isolates were unrelated, but
      clonal spread was seen; the 116 isolates distributed in 97 PFGE types, with the
      largest cluster consisting of 4 isolates (including three isolates from the same
      hospital with 100% similarity). Thirty-two isolates were pair-wise related, while
      the remaining isolates were clonally unrelated, as were all nine ESBL/MBL
      producers.

PMID- 23964750
TI  - Suicidal behaviours during treatment for first-episode psychosis: towards a
      comprehensive approach to service-based prevention.
AB  - AIM: Suicidal behaviours (suicide attempts and suicides) are common among
      individuals experiencing, or having recently experienced, a first-episode
      psychosis (FEP). Current interventions for suicidal behaviours are crisis driven
      and focused on hospital admission of patients at imminent risk of ending their
      lives. This paper aims to describe ideas for universal, selective and indicated
      strategies that may complement existing practices to suicide risk management in
      first-episode patients. METHODS: Key findings from the Suicidal Behaviours in FEP
      Project were used to develop suggested interventions. The project examined the
      temporal course of suicide risk, common characteristics of suicidal behaviours
      and predictors of suicidal behaviours in 699 patients with FEP. RESULTS: Key
      findings included: (i) 12% of FEP cohort engaged in suicidal behaviours during
      treatment (up to 3 years); (ii) first month of treatment conferred the highest
      suicide risk; (iii) 64% of suicidal behaviours were overdoses, usually on
      antipsychotics; (iv) 20% of suicidal behaviours occurred on psychiatric units and
      all involved hanging/strangulation; (v) most suicidal behaviours were impulsive,
      precipitated by psychosocial stressors and with serious intent; and (vi) proximal
      non-suicidal self-injurious behaviour and proximal negative life events were the
      strongest predictors. CONCLUSION: Comprehensive approach by mental health
      services to prevention of suicidal behaviours among first-episode patients could
      be facilitated by: delineating safe quantities of prescribed medications
      available to outpatients; regular audits of fixtures on inpatient units;
      enhancing risk recognition by family members; routinely monitoring suicide risk
      levels; developing crisis cards with all new FEP patients to facilitate help
      seeking during distress; and skills training programs targeting distress
      tolerance, interpersonal effectiveness and problem-solving.

PMID- 23964749
TI  - Structural determinants of drug partitioning in surrogates of phosphatidylcholine
      bilayer strata.
AB  - The knowledge of drug concentrations in bilayer headgroups, core, and at the
      interface between them is a prerequisite for quantitative modeling of drug
      interactions with many membrane-bound transporters, metabolizing enzymes and
      receptors, which have the binding sites located in the bilayer. This knowledge
      also helps understand the rates of trans-bilayer transport because balanced
      interactions of drugs with the bilayer strata lead to high rates, while excessive
      affinities for any stratum cause a slowdown. Experimental determination of
      bilayer location is so tedious and costly that the data are only available for
      some fifty compounds. To extrapolate these valuable results to more compounds at
      a higher throughput, surrogate phases have been used to obtain correlates of the
      drug affinities for individual strata. We introduced a novel system, consisting
      of a diacetyl phosphatidylcholine (DAcPC) solution with the water content of the
      fluid bilayer as the headgroup surrogate and n-hexadecane (C16) representing the
      core. The C16/DAcPC partition coefficients were measured for 113 selected
      compounds, containing structural fragments that are frequently occurring in
      approved drugs. The data were deconvoluted into the ClogP-based fragment
      solvation characteristics and processed using a solvatochromic correlation.
      Increased H-bond donor ability and excess molar refractivity of compounds promote
      solvation in the DAcPC phase as compared to bulk water, contrary to H-bond
      acceptor ability, dipolarity/polarizability, and volume. The results show that
      aromates have more balanced distribution in bilayer strata, and thus faster trans
      bilayer transport, than similar alkanes. This observation is in accordance with
      the frequent occurrence of aromatic rings in approved drugs and with the role of
      rigidity of drug molecules in promoting intestinal absorption. Bilayer locations,
      predicted using the C16/DAcPC system, are in excellent agreement with available
      experimental data, in contrast to other surrogate systems. 

PMID- 23964751
TI  - Accessibility to primary health care in Belgium: an evaluation of policies
      awarding financial assistance in shortage areas.
AB  - BACKGROUND: In many countries, financial assistance is awarded to physicians who
      settle in an area that is designated as a shortage area to prevent unequal
      accessibility to primary health care. Today, however, policy makers use fairly
      simple methods to define health care accessibility, with physician-to-population
      ratios (PPRs) within predefined administrative boundaries being overwhelmingly
      favoured. Our purpose is to verify whether these simple methods are accurate
      enough for adequately designating medical shortage areas and explore how these
      perform relative to more advanced GIS-based methods. METHODS: Using a
      geographical information system (GIS), we conduct a nation-wide study of
      accessibility to primary care physicians in Belgium using four different methods:
      PPR, distance to closest physician, cumulative opportunity, and floating
      catchment area (FCA) methods. RESULTS: The official method used by policy makers
      in Belgium (calculating PPR per physician zone) offers only a crude
      representation of health care accessibility, especially because large contiguous
      areas (physician zones) are considered. We found substantial differences in the
      number and spatial distribution of medical shortage areas when applying different
      methods. CONCLUSIONS: The assessment of spatial health care accessibility and
      concomitant policy initiatives are affected by and dependent on the methodology
      used. The major disadvantage of PPR methods is its aggregated approach, masking
      subtle local variations. Some simple GIS methods overcome this issue, but have
      limitations in terms of conceptualisation of physician interaction and distance
      decay. Conceptually, the enhanced 2-step floating catchment area (E2SFCA) method,
      an advanced FCA method, was found to be most appropriate for supporting areal
      health care policies, since this method is able to calculate accessibility at a
      small scale (e.g., census tracts), takes interaction between physicians into
      account, and considers distance decay. While at present in health care research
      methodological differences and modifiable areal unit problems have remained
      largely overlooked, this manuscript shows that these aspects have a significant
      influence on the insights obtained. Hence, it is important for policy makers to
      ascertain to what extent their policy evaluations hold under different scales of
      analysis and when different methods are used.

PMID- 23964753
TI  - Ring-contraction vs ring-expansion reactions of spiro-cyclopropanecarboxylated
      sugars.
AB  - Electrophilic ring opening of spiro-cyclopropanecarboxylated sugars followed by
      reaction with DBU revealed interesting ring-contraction and ring-expansion
      reactions depending on the substrate and the kind of hydroxyl protective group
      present adjacent to the spiro center. A stereoselective method for accessing a
      new class of carbon chain extended keto-furanoses and C-glycosylated bicyclic
      compounds is reported. 

PMID- 23964752
TI  - Efficacy and safety of diclofenac diethylamine 1.16% gel in acute neck pain: a
      randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Neck pain (NP) is a common musculoskeletal disorder in primary care
      that frequently causes discomfort. Non-steroidal anti-inflammatory drugs (NSAIDs)
      may be used to reduce neck pain and associated inflammation and facilitate
      earlier recovery. Topical diclofenac diethylamine (DDEA) 1.16% gel is clinically
      proven to be effective and well tolerated in acute and chronic musculoskeletal
      conditions, but until now no clinical data existed for its use in acute NP. The
      aim of this study was to assess the efficacy and safety of DDEA 1.16% gel
      compared with placebo gel in acute NP. METHODS: In a randomized, double-blind,
      placebo-controlled study, patients with acute NP (n = 72) were treated with DDEA
      1.16% gel (2 g, 4x/day, for 5 days) or placebo. Efficacy assessments included
      pain-on-movement (POM), pain-at-rest (PAR), functional neck disability index
      (NDI) and response to treatment (decrease in POM by 50% after 48 h). Adverse
      events (AEs) were recorded throughout the study. RESULTS: The primary outcome,
      POM at 48 h, was statistically significantly lower with DDEA gel (19.5 mm) vs.
      placebo (56.9 mm) (p < 0.0001), representing a clinically relevant decrease from
      baseline (75% vs. 23%, respectively). All POM scores were significantly lower
      with DDEA gel vs. placebo from 1 h, as were PAR and NDI scores from first
      assessment (24 h) onwards (all p < 0.0001). Response to treatment was
      significantly higher with DDEA gel (94.4%) vs. placebo (8.3%) (p < 0.0001). There
      were no AEs with DDEA gel. CONCLUSIONS: DDEA 1.16% gel, which is available over
      the-counter, was effective and well tolerated in the treatment of acute neck
      pain. The tools used to assess efficacy suggest that it quickly reduced neck pain
      and improved neck function. However, questions remain regarding the comparability
      and validity of such tools. Further studies will help ascertain whether DDEA
      1.16% gel offers an alternative treatment option in this common, often
      debilitating condition. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
      NCT01335724.

PMID- 23964754
TI  - AA amyloidosis as a complication of primary lymphedema.
AB  - Primary lymphedema is a rare disease caused by a disorder of lymphangiogenesis.
      Clinical presentation and age at onset are variable. AA amyloidosis is usually
      due to chronic inflammatory diseases, malignant tumors or less frequently chronic
      infectious diseases. We report here the first two cases of AA amyloidosis present
      with renal failure and nephrotic syndrome in patients with primary lymphedema
      induced chronic leg ulcers. The first patient was a 62-year-old female who
      presented with chronic untreated leg ulcers for 8 years secondary to primary
      lymphedema. A kidney biopsy done for nephrotic syndrome allowed the diagnosis of
      AA amyloidosis. The second patient was a 54-year-old male who presented with
      hereditary lymphedema and elephantiasis since the age of 12. A salivary gland
      biopsy allowed the diagnosis of AA amyloidosis. Renal function deteriorated
      progressively needing chronic haemodialysis. Chronic leg ulcers have been rarely
      reported to induce AA amyloidosis. Only five other cases have been reported in
      the literature, but none of them with chronic lymphedema. We believe that the
      relation between lymphedema, chronic leg ulcers and AA amyloidosis is
      underestimated.

PMID- 23964755
TI  - Role of natriuretic peptide to predict cardiac abnormalities in patients with
      hereditary transthyretin amyloidosis.
AB  - BACKGROUND: Familial amyloid polyneuropathy (FAP) mainly targets the peripheral
      nervous system and heart. Early noninvasive detection of cardiac impairment is
      critical for therapeutic management. AIM: To assess if amino-terminal pro-brain
      natriuretic peptide (NT-proBNP) or troponin T (cTnT) can predict
      echocardiographic left-ventricle (LV) impairment in FAP. METHODS: Thirty-six
      asymptomatic carriers and patients with FAP had echocardiographic measurement of
      left-ventricular (LV) systolic function, hypertrophy (LVH) and estimation of
      filling pressure (FP). RESULTS: Overall, median age, NT-proBNP, and LV ejection
      fraction were, respectively, 59 years (41-74), 323 pg/ml (58-1960), and 60% (51
      66). Twelve patients had increased cTnT. Prevalence of ATTR gene mutations was
      53% for Val30Met. Four individuals were asymptomatic, 6 patients had isolated
      neurological clinical signs, and 26 had echo-LV abnormalities. The ROC curve
      identified NT-proBNP patients with echo-LV abnormalities (area: 0.92; (0.83
      0.99), p = 0.001) at a threshold >82 pg/ml with a sensitivity of 92%, and a
      specificity of 90%. Increased in NT-proBNP occurred in patients with SD and/or
      LVH with or without increase in FP. Elevated cTnT (>0.01 ng/ml) was only observed
      in patients with LVH and systolic dysfunction, with or without FP. CONCLUSION: In
      FAP, NT-proBNP was associated with cardiac impairment suggesting that NT-proBNP
      could be used in carriers or in FAP patients with only neurologic symptoms for
      identifying the appropriate time to start cardiac echocardiographic assessment
      and follow-up. cTnT identified patients with severe cardiac disease.

PMID- 23964756
TI  - Learning without Memory.
AB  - After a CS-US learning trial, powerful feedback (FB) selectively modulates the
      hedonic value of the US, perhaps affecting the CS as well. FB. operates
      regardless of the subject's attributions or awareness, often influencing the
      subject's unconscious motives in a single trial. Most of the evidence comes from
      feeding research where the taste US and the internal FB are independently
      manipulated, but similar influences are at work with painful, thermal and sexual
      USs in a wide variety of species including humans. Implications for cognitive
      theorizing and neural research on mechanisms of learning are discussed. 

PMID- 23964757
TI  - The perception of structure from visual motion in monkey and man.
AB  - The ability to perceive structure using motion information was examined using a
      reaction time task with two primate species. Homo sapien and Macaca mulatta
      subjects were quantitatively tested under identical conditions to detect the
      change from a control unstructured to a test structured motion stimulus. The
      structures underlying the test were rotations of a plane, expansion of a plane,
      and a rotation of a three-dimensional cylinder. On many of the stimulus
      conditions, the two species performed similarly, although there were some species
      differences. These differences may be due to the extensive training of the
      monkeys or the use of different cognitive strategies by the human subjects. These
      data provide support for the existence of a neural mechanism that uses flow
      fields to construct two- or three-dimensional surface representations. 

PMID- 23964758
TI  - Visual Object Representation: Interpreting Neurophysiological Data within a
      Computational Framework.
AB  - Significant progress has been made in understanding vision by combining
      computational and neuroscientific constraints. However, for the most part these
      integrative approaches have been limited to low-level visual processing. Recent
      advances in our understanding of high-level vision in the two separate
      disciplines warrant an attempt to relate and integrate these results to extend
      our understanding of vision through object representation and recognition. This
      paper is an attempt to contribute to this goal, by using a computational
      framework arising out of computer vision research to organize and interpret human
      and primate neurophysiology and neuropsychology. 

PMID- 23964759
TI  - Event-related potentials to infrequent changes in synthesized phonetic stimuli.
AB  - Event-related potentials (ERPs) to synthetic consonant-vowel syllables were
      recorded. Infrequent changes in such a syllable elicited a "mismatch negativity"
      as well as an enhanced N100 component of the ERP even when subjects did not pay
      attention to the stimuli. Both components are probably generated in the
      supratemporal auditory cortex suggesting that in these areas there are neural
      networks that are automatically activated by speech-specific auditory stimulus
      features such as formant transitions. 

PMID- 23964760
TI  - Thalamic and cortical mechanisms of attention suggested by recent positron
      emission tomographic experiments.
AB  - An attention mechanism in the pulvinar nucleus of the thalamus appears to be
      involved in the filtering of a location in a cluttered visual field, according to
      recent PET data. The mechanism in the pulvinar is assumed to be a particular type
      of circuit that reciprocally connects thalamic relay cells to cortical cells.
      This circuit, which is characteristic of thalamic nuclei in general, appears to
      embody an algorithm that enhances firing in a target set of cells while
      inhibiting firing in the surrounding set of cells. Recent PET studies have also
      identified specific areas of cortex that show increased blood flow when humans
      expect to process particular aspects of visual objects, such as location, shape,
      color, and movement velocity. An expectation for a particular feature can be
      regarded as a peaked activity distribution across cortical synaptic space that
      increases the effectiveness (accuracy and speed) of the perception of that
      feature and features similar to that feature. The expectation process is assumed
      to be generated by a thalamic enhancement circuit, which in turn is driven by a
      cognitive procedure, apparently located in the anterior cingulate area of the
      cortex. The selection of a particular cognitive procedure is assumed to depend on
      the momentary relative motivational value associated with it by means of
      connections to deeper limbic structures. Under usual conditions, the procedure
      having the dominant motivational value is the one selected. 

PMID- 23964762
TI  - Seeing contour and colour.

PMID- 23964761
TI  - Anterior Frontal Cortex and the Effect of Proactive Interference in Paired
      Associate Learning: A DC Potential Study.
AB  - This contribution focuses on neurophysiological correlates of the cerebral
      processes subserving the control of proactive interference. Event-related
      negative shifts of the scalp-recorded cortical steady potential (negative DC
      shifts) were measured in 17 right-handed normals during two tasks of paired
      associate learning. The control condition was a standard word pair learning task
      in which unrelated word pairs were presented. In the experimental condition,
      proactive interference was maximized by presenting very similar words and by
      requiring negative transfer, i.e., by having them reappear, but in different
      pairings. Proactive interference leads to increased anterior frontal negative DC
      shifts. Furthermore, centrotemporal negative DC shifts predicted subsequent cued
      recall performance. In spite of elaborative strategies, an effect of subsequent
      mnestic performance on the P300 was observed. 

PMID- 23964764
TI  - Foundations of cognitive science.

PMID- 23964763
TI  - The remembered present: a biological theory of consciousness.

PMID- 23964765
TI  - An invitation to cognitive science.

PMID- 23964766
TI  - Microbiota in health and irritable bowel syndrome: current knowledge,
      perspectives and therapeutic options.
AB  - The gastrointestinal tract is a natural reservoir of microbiota. The gut is germ
      free at birth, but rapidly becomes host to various bacteria establishing a
      progressively mutual relationship. The composition of gut microbiota is
      individual-specific and depends on the genotype of the host and environmental
      factors. Novel techniques have been used to characterize gastrointestinal
      microbiota, including genomic approaches. The bacterial profile shows that
      dominant and minor phyla are present in the gastrointestinal tract. From the
      proximal to the distal segments of the gut the bacterial density gradually
      increases, reaching an estimated 10(11) to 10(12) bacteria per gram of colonic
      content. Dynamic interactions between gut and microbiota play a physiological
      role in metabolic, protective and structural functions, while dysbiosis
      contributes to several diseases. Microbiota appear to play a role in IBS, where
      qualitative and quantitative changes of bacteriaoccur in IBS subtypes. Initial
      therapeutic approaches in IBS have focused on microbiota. The relationship
      between perturbations of the microbiota, mucosal inflammation and IBS remains to
      be further investigated.

PMID- 23964767
TI  - Vomiting: a physiological response to acidosis?

PMID- 23964768
TI  - Ernest L. Mazzaferri, MD, MACP (1936-2013).
AB  - Professor and physician Dr. Ernest L. Mazzaferri Sr. passed away on May 14, 2013,
      at 76 years of age ( 1 , 2 ). Ernie is remembered as a caring and talented
      physician, an accomplished scholar and educator, as well as a loving husband,
      father, and grandfather. He was a luminary figure, and few people have had a
      greater impact in thyroidology in recent decades. Here we include reflections
      from a few of us that knew him, as well as commentaries from people who did not.
      Ernie's passion was caring for patients and how to improve their care. Our goal
      is to pay tribute and memorialize the person we knew and the impact that he had
      on patients around the world through his dedication to research, lecturing, and
      writing that achieved remarkable global influence. 

PMID- 23964769
TI  - The launch of the Chinese version of Thyroid: an earthshaking event.

PMID- 23964772
TI  - Current phase II clinical data for ridaforolimus in cancer.
AB  - INTRODUCTION: The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway plays a
      critical role in controlling cellular metabolism, proliferation and cell cycle
      regulation. Constitutive activation of this pathway has been demonstrated in many
      tumor types. Targeting the PI3K/AKT/mTOR pathway is of increasing therapeutic
      interest. AREAS COVERED: Ridaforolimus belongs to a class of agents known as the
      rapalogs, first-generation mTOR inhibitors, which inhibit mTORC1, a part of the
      mTOR complex. Both oral and intravenous formulations of this agent have been
      tested in Phase II clinical trials for the treatment of solid tumors and
      hematologic malignancies. Promising results have been seen in endometrial cancer
      and soft tissue and bone sarcomas. EXPERT OPINION: This article summarizes the
      current clinical and biological data on the use of ridaforolimus emerging from
      these Phase II studies, and provides potential advantages and drawbacks of the
      mTOR inhibitors in the current clinical practice.

PMID- 23964773
TI  - DNA as a molecular wire: distance and sequence dependence.
AB  - Functional nanowires and nanoelectronics are sought for their use in next
      generation integrated circuits, but several challenges limit the use of most
      nanoscale devices on large scales. DNA has great potential for use as a molecular
      wire due to high yield synthesis, near-unity purification, and nanoscale self
      organization. Nonetheless, a thorough understanding of ground state DNA charge
      transport (CT) in electronic configurations under biologically relevant
      conditions, where the fully base-paired, double-helical structure is preserved,
      is lacking. Here, we explore the fundamentals of CT through double-stranded DNA
      monolayers on gold by assessing 17 base pair bridges at discrete points with a
      redox active probe conjugated to a modified thymine. This assessment is performed
      under temperature-controlled and biologically relevant conditions with cyclic and
      square wave voltammetry, and redox peaks are analyzed to assess transfer rate and
      yield. We demonstrate that the yield of transport is strongly tied to the
      stability of the duplex, linearly correlating with the melting temperature.
      Transfer rate is found to be temperature-activated and to follow an inverse
      distance dependence, consistent with a hopping mechanism of transport. These
      results establish the governing factors of charge transfer speed and throughput
      in DNA molecular wires for device configurations, guiding subsequent application
      for nanoscale electronics. 

PMID- 23964771
TI  - A nucleolar AAA-NTPase is required for parasite division.
AB  - Apicomplexa division involves several distinct phases shared with other eukaryote
      cell cycles including a gap period (G1) prior to chromosome synthesis, although
      how progression through the parasite cell cycle is controlled is not understood.
      Here we describe a cell cycle mutant that reversibly arrests in the G1 phase. The
      defect in this mutant was mapped by genetic complementation to a gene encoding a
      novel AAA-ATPase/CDC48 family member called TgNoAP1. TgNoAP1 is tightly regulated
      and expressed in the nucleolus during the G1/S phases. A tyrosine to a cysteine
      change upstream of the second AAA+ domain in the temperature sensitive TgNoAP1
      allele leads to conditional protein instability, which is responsible for rapid
      cell cycle arrest and a primary defect in 28S rRNA processing as confirmed by
      knock-in of the mutation back into the parent genome. The interaction of TgNoAP1
      with factors of the snoRNP and R2TP complexes indicates this protein has a role
      in pre-rRNA processing. This is a novel role for a cdc48-related chaperone
      protein and indicates that TgNoAP1 may be part of a dynamic mechanism that senses
      the health of the parasite protein machinery at the initial steps of ribosome
      biogenesis and conveys that information to the parasite cell cycle checkpoint
      controls. 

PMID- 23964774
TI  - Literary responsibility--everyone has a role to play.

PMID- 23964776
TI  - Marginal fit of implant-supported all-ceramic zirconia frameworks.
AB  - This study evaluated the effect of fabrication techniques and cyclic loading on
      the vertical marginal fit of implant-supported fixed partial denture (FPD)
      frameworks. Thirty implant-supported 3-unit FPD frameworks were fabricated on a
      model system, divided into 3 equal groups (n = 10). The first group (control) was
      constructed from base metal alloy; the other 2 test groups were constructed from
      all-ceramic zirconia using a computer-aided design/computer-aided manufacturing
      (CAD/CAM) Cerec 3 system and a copy milling (Zirkonzahn) system. A cyclic load of
      200 N was applied to each framework for up to 50,000 cycles. Linear measurements
      were made in micrometers of the vertical gap between the framework and the
      implant-supported abutment at 16 predetermined points before and after cyclic
      loading. The frameworks were viewed using scanning electron microscopy to inspect
      any fractographic features. One-way analysis of variance was performed to compare
      the marginal discrepancy values of the control and the 2 test groups and for each
      group; a t test was applied to determine whether significant changes in the fit
      were observed after cyclic loading (alpha = 0.05). The CAD/CAM group showed
      significantly higher marginal gap mean values (80.58 MUm) than the Zirkonzahn and
      control groups (50.33 MUm and 42.27 MUm, respectively) with no significant
      difference. After cyclic loading, the CAD/CAM group recorded the highest marginal
      gap mean value (91.50 +/- 4.260 MUm) followed by control group (72.00 +/- 2.795
      MUm); the Zirkonzahn group recorded the lowest marginal gap (65.37 +/- 6.138
      MUm). Cyclic loading significantly increased the marginal gap mean values in the
      control group only. A marginal chip was observed in one of the CAD/CAM ceramic
      frameworks. Within the limitations of this study, the fabrication technique
      influenced the marginal fit of the implant-supported 3-unit FPD frameworks.
      Cyclic loading failed to change the fit of all-ceramic zirconia frameworks,
      whereas significant changes were found in the metal frameworks.

PMID- 23964777
TI  - Autologous dental pulp stem cells in regeneration of defect created in canine
      periodontal tissue.
AB  - This study aimed to investigate effects of dental pulp stem cells (DPSCs) on
      regeneration of a defect experimentally created in the periodontium of a canine
      model. Surgically created mesial 3-walled periodontal defects with ligature
      induced periodontitis were produced bilaterally in the first lower premolar teeth
      of 10 mongrel dogs. Simultaneously, DPSCs were derived from the maxillary
      premolar teeth of the same dogs. Four weeks after creation of the periodontitis
      model, autologous passaged-3 DPSCs combined with Bio-Oss were implanted on one
      side as the test group. On the other side, only Bio-Oss was implanted as a
      control. Eight weeks after surgery, regeneration of the periodontal defects was
      evaluated histologically and histomorphometrically in terms of bone, periodontal
      ligament (PDL), and cement formation. Histologically, in all test specimens (10
      defects), regeneration of cementum, bone, and PDL was observed. In the control
      groups, although we observed the regeneration of bone in all defects, the
      formation of cementum was seen in 9 defects and PDL was seen in 8 defects.
      Histomorphometric analyses showed that the amount of regenerated cementum and PDL
      in the test groups (3.83 +/- 1.32 mm and 3.30 +/- 1.12 mm, respectively) was
      significantly higher than that of the control groups (2.42 +/- 1.40 mm and 1.77
      +/- 1.27 mm, respectively; P < .05). A biocomplex consisting of DPSCs and Bio-Oss
      would be promising in regeneration of periodontal tissues.

PMID- 23964778
TI  - Histologic and biomechanical evaluation of 2 resorbable-blasting media implant
      surfaces at early implantation times.
AB  - This study evaluated 3 implant surfaces in a dog model: (1) resorbable-blasting
      media + acid-etched (RBMa), alumina-blasting + acid-etching (AB/AE), and AB/AE +
      RBMa (hybrid). All of the surfaces were minimally rough, and Ca and P were
      present for the RBMa and hybrid surfaces. Following 2 weeks in vivo, no
      significant differences were observed for torque, bone-to-implant contact, and
      bone-area fraction occupied measurements. Newly formed woven bone was observed in
      proximity with all surfaces. 

PMID- 23964779
TI  - Efficacy of guided bone regeneration using composite bone graft and resorbable
      collagen membrane in Seibert's Class I ridge defects: radiological evaluation.
AB  - The purpose of the study was to evaluate radiologically the efficacy of guided
      bone regeneration using composite bone graft (autogenous bone graft and anorganic
      bovine bone graft [Bio-Oss]) along with resorbable collagen membrane (BioMend
      Extend) in the augmentation of Seibert's class I ridge defects in maxilla. Bone
      width was evaluated using computerized tomography at day 0 and at day 180 at 2
      mm, 4 mm, and 6 mm from the crest. There was a statistically significant increase
      in bone width between day 0 and day 180 at 2 mm, 4 mm, and 6 mm from the crest.
      The results of the study demonstrated an increase in bone width of Seibert's
      class I ridge defects in the maxilla of the study patients. 

PMID- 23964780
TI  - Osseointegration of dental implants and osteonecrosis of the jaw in patients
      treated with bisphosphonate therapy: a systematic review.
AB  - Bisphosphonate (BP) drugs are a commonly prescribed group of medications used in
      the treatment of metabolic and oncologic bone disorders. The aim of this study
      was to conduct a systematic review in order to evaluate whether patients on BP
      therapy are appropriate candidates for dental implants as compared to patients
      not taking BP drugs with respect to successful implant osseointegration and the
      risk of developing bisphosphonate-related osteonecrosis of the jaw. Based on the
      current literature, a history of oral or intravenous BP use is not an absolute
      contraindication for dental implant placement, and dental implants can
      osseointegrate successfully in this patient population. Importantly, the studies
      currently available on this topic are of moderate to weak strength of evidence
      with inherent bias and limitations, and hence results must be interpreted in this
      context. Well-controlled studies with higher strength of evidence and larger
      population sizes are required to address this topic more accurately in the
      future. 

PMID- 23964782
TI  - SILAC-based proteome analysis of Starmerella bombicola sophorolipid production.
AB  - Starmerella (Candida) bombicola is the biosurfactant-producing species that
      caught the greatest deal of attention in the academic and industrial world due to
      its ability of producing large amounts of sophorolipids. Despite its high
      economic potential, the biochemistry behind the sophorolipid biosynthesis is
      still poorly understood. Here we present the first proteomic characterization of
      S. bombicola for which we created a lys1Delta mutant to allow the use of SILAC
      for quantitative analysis. To characterize the processes behind the production of
      these biosurfactants, we compared the proteome of sophorolipid producing (early
      stationary phase) and nonproducing cells (exponential phase). We report the
      simultaneous production of all known enzymes involved in sophorolipid
      biosynthesis including a predicted sophorolipid transporter. In addition, we
      identified the heme binding protein Dap1 as a possible regulator for Cyp52M1. Our
      results further indicate that ammonium and phosphate limitation are not the sole
      limiting factors inducing sophorolipid biosynthesis. 

PMID- 23964783
TI  - Charge transfer in E. coli DNA photolyase: understanding polarization and
      stabilization effects via QM/MM simulations.
AB  - We study fast hole transfer events in E. coli DNA photolyase, a key step in the
      photoactivation process, using a multiscale computational method that combines
      nonadiabatic propagation schemes and linear-scaling quantum chemical methods with
      molecular mechanics force fields. This scheme allows us to follow the time
      dependent evolution of the electron hole in an unbiased fashion; that is, no
      assumptions about hole wave function localization, time scale separation, or
      adiabaticity of the process have to be made beforehand. DNA photolyase
      facilitates an efficient long-range charge transport between its flavin adenine
      dinucleotide (FAD) cofactor and the protein surface via a chain of evolutionary
      conserved Trp residues on the sub-nanosecond time scale despite the existence of
      multiple potential trap states. By including a large number of aromatic residues
      along the charge transfer pathway into the quantum description, we are able to
      identify the main pathway among alternative possible routes. The simulations show
      that charge transfer, which is extremely fast in this protein, occurs on the same
      time scale as the protein response to the electrostatic changes; that is, time
      scale separation as often presupposed in charge transfer studies seems to be
      inappropriate for this system. Therefore, coupled equations of motion, which
      propagate electrons and nuclei simultaneously, appear to be necessary. The
      applied computational model is shown to capture the essentials of the reaction
      kinetics and thermodynamics while allowing direct simulations of charge transfer
      events on their natural time scale. 

PMID- 23964784
TI  - Singlet oxygen-induced photodegradation of the polymers and dyes in optical
      sensing materials and the effect of stabilizers on these processes.
AB  - A comprehensive study of photodegradation processes in optical sensing materials
      caused by photosensitized singlet oxygen in different polymers is presented. The
      stabilities of the polymers are accessed in the oxygen consumption measurements
      performed with help of optical oxygen sensors. Polystyrene and
      poly(phenylsilesquioxane) are found to be the most stable among the polymers
      investigated, whereas poly(2,6-dimethyl-p-phenylene oxide) and particularly
      poly(methyl methacrylate) and their derivatives show the fastest oxygen
      consumption. The effect of the stabilizers (singlet oxygen quenchers) on the
      oxygen consumption rates, the photostability of the sensitizer, and the total
      photon emission (TPE) by singlet oxygen is studied. 1,4-Diazabicyclo[2.2.2]octane
      (DABCO) was found to significantly reduce both the TPE and the oxygen consumption
      rates, indicating its role as a physical quencher of singlet oxygen. The addition
      of DABCO also significantly improved the photostability of the sensitizer. The N
      alkylated derivative of DABCO and DABCO covalently grafted to the polystyrene
      backbone are prepared in an attempt to overcome the volatility and water
      solubility of the quencher. These derivatives as well as other tertiary amines
      investigated were found to be inefficient as stabilizing agents, and some of them
      even negatively affected the oxygen consumption rates. 

PMID- 23964786
TI  - Toll-like receptor 9 SNPs are susceptible to the development and progression of
      membranous glomerulonephritis: 27 years follow-up in Taiwan.
AB  - The purpose of this study was to determine whether toll-like receptors 9 (TLR9)
      gene polymorphisms (rs352139 and rs352140) were markers of susceptibility to the
      development and progression of membranous nephropathy (MGN) in Taiwanese
      patients. The polymorphisms were investigated by polymerase chain reaction in 397
      Taiwanese individuals (134 MGN patients and 263 controls). Patients with
      malignancy, chronic infectious diseases, lupus nephritis, or drug-induced
      secondary MGN were excluded from the study. Data showed AA genotype at rs352139
      SNP or GG genotype at rs352140 SNP may indicate higher risk for MGN (odds ratio
      [OR] = 1.55; 95% confidence interval [CI] = 1.02-2.35, at rs352139 SNP; OR =
      1.57; 95% CI = 1.03-2.39, at rs352140 SNP). However, MGN patients with A-G
      haplotype were susceptible for decreased creatinine clearance rate and for
      seriously tubule-interstitial fibrosis. The result suggests for the first time
      that TLR9 (rs352139 and rs352140) polymorphisms may contribute to the development
      and progression of MGN.

PMID- 23964785
TI  - The associations of body mass index with physical and mental aspects of health
      related quality of life in Chinese patients with type 2 diabetes mellitus:
      results from a cross-sectional survey.
AB  - BACKGROUND: This study aimed to determine the associations of various clinical
      factors with generic health-related quality of life (HRQOL) scores among Hong
      Kong Chinese patients with type 2 diabetes mellitus (T2DM) in the outpatient
      primary care setting using the short-form 12 (SF-12). METHODS: A cross-sectional
      survey of 488 Chinese adults with T2DM recruited from a primary care outpatient
      clinic was conducted from May to August 2008. Data on the standard Chinese (HK)
      SF-12 Health Survey and patients' socio-demographics were collected from face-to
      face interviews. Glycaemic control, body mass index (BMI), chronic co
      morbidities, diabetic complications and treatment modalities were determined for
      each patient through medical records. Associations of socio-demographic and
      clinical factors with physical component summary (PCS-12) and mental component
      summary scores (MCS-12) were evaluated using multiple linear regression. RESULTS:
      The socio-demographic correlates of PCS-12 and MCS-12 were age, gender and BMI.
      After adjustment for socio-demographic variables, the BMI was negatively
      associated with PCS-12 but positively associated with MCS-12. The presence of
      diabetic complications was associated with lower PCS-12 (regression coefficient:
      3.0 points, p < 0.05) while being on insulin treatment was associated with lower
      MCS-12 (regression coefficient:-5.8 points, p < 0.05). In contrast, glycaemic
      control, duration of T2DM and treatment with oral hypoglycaemic drugs were not
      significantly associated with PCS-12 or MCS-12. CONCLUSIONS: Among T2DM subjects
      in the primary care setting, impairments in the physical aspect of HRQOL were
      evident in subjects who were obese or had diabetic complications whereas defects
      in the mental aspect of HRQOL were observed in patients with lower BMI or
      receiving insulin injections.

PMID- 23964787
TI  - Interaction of organic solvents with the epicuticular wax layer of wheat leaves.
AB  - After foliar application, compounds that are not absorbed into leaves can be
      removed from the leaf surface by dipping or rinsing in dilutions of organic
      solvents in water. However, interactions between solvent mixtures and the
      epicuticular wax layer have received little attention, and information on
      potential physical and chemical intactness of the plant surface following
      application of solvents is limited. In this study, wheat leaves were dipped in
      organic solvents at different dilutions with water, and the major component of
      the leaf epicuticular wax layer, 1-octacosanol, was analyzed to assess damage to
      the wax layer. Dipping leaves in dilutions of organic solvent higher than 60% by
      volume resulted in only negligible or low levels of 1-octacosanol extraction,
      while no 1-octacosanol was detected in any mixtures containing less than 40%
      organic solvent. Furthermore, analysis of leaf surfaces by scanning electron
      microscopy showed structural intactness of the epicuticular wax layer when
      organic solvent mixtures were used. Therefore, our results demonstrate that the
      epicuticular wax layer of wheat leaves is not altered physically or chemically by
      organic solvent solutions up to 40% by volume. These findings validate the use of
      solvent washing procedures to assess unabsorbed compounds on wheat leaf surfaces.

PMID- 23964788
TI  - Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and
      its antiproliferative activity.
AB  - Histone N(epsilon)-methyl lysine demethylases KDM2/7 have been identified as
      potential targets for cancer therapies. On the basis of the crystal structure of
      KDM7B, we designed and prepared a series of hydroxamate analogues bearing an
      alkyl chain. Enzyme assays revealed that compound 9 potently inhibits KDM2A,
      KDM7A, and KDM7B, with IC50s of 6.8, 0.2, and 1.2 MUM, respectively. While
      inhibitors of KDM4s did not show any effect on cancer cells tested, the KDM2/7
      subfamily inhibitor 9 exerted antiproliferative activity, indicating the
      potential for KDM2/7 inhibitors as anticancer agents. 

PMID- 23964789
TI  - Coenzyme Q10 supplementation in infertile men with low-grade varicocele: an open,
      uncontrolled pilot study.
AB  - Many conditions associated with male infertility are inducers of oxidative
      stress, including varicocele. Antioxidants, such as coenzyme Q10, may be useful
      in this case. To evaluate the antioxidant capacity of seminal plasma of infertile
      men with varicocele before and after an oral supplementation with coenzyme Q10 ,
      38 patients were recruited from a pilot clinical trial. A standard semen analysis
      was also performed at baseline and 3 months after an oral supplementation with
      exogenous coenzyme Q10 100 mg per die. Seminal plasma antioxidant capacity was
      measured using a spectroscopic method. Coenzyme Q10 therapy improved semen
      parameters and antioxidant status. This study highlights the importance of
      oxidative stress in the pathogenesis of male infertility, namely in varicocele,
      and strengthens the possibility of the usefulness of the antioxidant therapy.

PMID- 23964791
TI  - 25 years of SMIT.

PMID- 23964792
TI  - 25 years of SMIT: the past, the present, and the future of minimally invasive
      therapy.
AB  - A quarter of a century has passed since the Society of Minimally Invasive Therapy
      (SMIT) was founded in 1989 with the aim to provide a platform to promote the
      development of minimally invasive therapy and the new instruments and devices
      needed to carry out the new surgical techniques. Both the founder of the society,
      British urologist John EA Wickham, and the German surgeon Gerhard F Buess, who
      was one of the leading members from the beginning, conceived SMIT as an
      interdisciplinary forum to promote the cooperation between physicians from
      various surgical specialties, but also medical engineers, resp. medical device
      manufacturers, whose expertise was needed to build the instruments that had to be
      developed to carry out the new concept of surgery. In this paper we outline the
      history of SMIT over the past 25 years in order to highlight both the ideas
      behind the society and the dedication of the people who shaped it.

PMID- 23964790
TI  - Therapeutic efficacy and safety of botulinum toxin type A in trigeminal
      neuralgia: a systematic review.
AB  - Trigeminal neuralgia is a common disorder caused mainly by compression of the
      trigeminal nerve root by an overlying blood vessel. Pharmacotherapy and surgery
      are ineffective or unsuitable in many patients. Therefore, other therapeutic
      modalities have been tried, including injection of botulinum toxin type A (BTX
      A). This study aims to systematically review the therapeutic efficacy and safety
      of BTX-A in trigeminal neuralgia. PubMed, EMBASE, Cochrane Library Clinical
      Trials and Web of Science from January 1966 to March 2013 were searched with the
      terms of "botulinum toxin" AND "trigeminal neuralgia", and references of related
      articles were traced. Data on the efficacy and safety of BTX-A in this disorder
      were extracted and analyzed by at least 2 reviewers. Data for individual studies
      were reported, and pooled data were analyzed if appropriate. Five prospective
      studies and one double-blind, randomized, placebo-controlled study were
      identified. Response was achieved in approximately 70-100% of patients, and the
      mean pain intensity and frequency were reduced by approximately 60-100% at 4
      weeks after treatment in most studies. Major adverse events were not reported.
      Available studies show BTX-A may be effective in treatment of trigeminal
      neuralgia. However, well-designed randomized, controlled, double-blinded trial is
      still lacking. Future BTX-A treatment studies on optimal dose, duration of the
      therapeutic efficacy, common AEs, and the time and indications for repeat
      injection would be promising. 

PMID- 23964793
TI  - The past, present and future of minimally invasive endoscopy in gynecology: a
      review and speculative outlook.
AB  - Over the last twenty-five years, minimally invasive surgery (MIS) has evolved in
      a relatively short period of time to overtake the centuries-old visionary and
      pioneering groundwork of our outstanding colleagues in all surgical disciplines.
      This overview on the development of gynecological endoscopy, at the invitation of
      SMIT, highlights past achievements and describes present challenges. It
      emphasizes future opportunities and possibilities to foster interdisciplinary
      collaboration and integrate emerging endoscopic, imaging and stereotactic
      surgical technologies to improve patient safety, enhance quality of care and
      advance surgical education. This article will introduce younger colleagues to the
      exciting world of contemporary gynecologic endoscopy and help them appreciate the
      immense technology-laden opportunities that the future holds for those who are
      prepared to follow in the footsteps and aspirations of our founding surgical
      colleagues.

PMID- 23964794
TI  - The past, present and future of minimally invasive spine surgery: a review and
      speculative outlook.
AB  - In the last 25 years of spinal surgery, tremendous improvements have been made.
      The development of smart technologies with the overall aim of reducing surgical
      trauma has resulted in the concept of minimally invasive surgical techniques.
      Enhancements in microsurgery, endoscopy and various percutaneous techniques, as
      well as improvement of implant materials, have proven to be milestones. The
      advancement of training of spine surgeons and the integration of image guidance
      with precise intraoperative imaging, computer- and robot-assisted treatment
      modalities constitute the era of reducing treatment morbidity in spinal surgery.
      This progress has led to the present era of preserving spinal function. The
      promise of the continuing evolution of spinal surgery, the era of restoring
      spinal function, already appears on the horizon. The current state of minimally
      invasive spine surgery is the result of a long-lasting and consecutive
      development of smart technologies, along with stringent surgical training
      practices and the improvement of instruments and techniques. However, much effort
      in research and development is still mandatory to establish, maintain and evolve
      minimally invasive spine surgery. The education and training of the next
      generation of highly specialized spine surgeons is another key point. This paper
      will give an overview of surgical techniques and methods of the past 25 years,
      examine what is in place today, and suggest a projection for spine surgery in the
      coming 25 years by drawing a connection from the past to the future.

PMID- 23964795
TI  - The past, present and future of minimally invasive therapy in endovascular
      interventions: a review and speculative outlook.
AB  - Cardiovascular disease is a leading cause of death in all developed countries. In
      response to this need, endovascular management techniques have been developed
      across a large range of medical specialties. Minimally invasive percutaneous
      interventions were initially complex and challenging, but with the continued
      development of equipment and expertise their use has become routine in many
      fields. With routine use, it has become important to establish the safety and
      efficacy of endovascular treatments against the respective "gold standard"
      procedures, especially in light of their initial intended use for the management
      of patients at unacceptably high risk for standard therapy only. Such evaluation
      has to take into account the variety and diversity of devices and techniques, as
      well as the effects of operator dependability. Endovascular techniques are
      increasingly recognised as valid alternative management options for a variety of
      conditions, and it is anticipated that the current trend towards minimally
      invasive techniques will continue in the future, with moves towards increasingly
      complex endovascular techniques and hybrid interventions.

PMID- 23964796
TI  - Preparation and characterization of novel magnetic nano-in-microparticles for
      site-specific pulmonary drug delivery.
AB  - We propose the use of novel inhalable nano-in-microparticles (NIMs) for site
      specific pulmonary drug delivery. Conventional lung cancer therapy has failed to
      achieve therapeutic drug concentrations at tumor sites without causing adverse
      effects in healthy tissue. To increase targeted drug delivery near lung tumors,
      we have prepared and characterized a magnetically responsive dry powder vehicle
      containing doxorubicin. A suspension of lactose, doxorubicin and Fe3O4
      superparamagnetic iron oxide nanoparticles (SPIONs) were spray dried. NIMs were
      characterized for their size and morphological properties by various techniques:
      dynamic light scattering (DLS) and laser diffraction (LS) to determine
      hydrodynamic size of the SPIONs and the NIMs, respectively; next generation
      cascade impactor (NGI) to determine the aerodynamic diameter and fine particle
      fraction (FPF); scanning (SEM) and transmission (TEM) electron microscopy to
      analyze particle surface morphology; electron dispersive X-ray spectroscopy (EDS)
      to determine iron loading in NIMs; inductively coupled plasma atomic emission
      spectroscopy (ICP-AES) and superconducting quantum interference device (SQUID) to
      determine Fe3O4 content in the microparticles; and high performance liquid
      chromatography (HPLC) to determine doxorubicin loading in the vehicle. NIMs
      deposition and retention near a magnetic field was performed using a proof-of
      concept cylindrical tube to mimic the conducting airway deposition. The
      hydrodynamic size and zeta potential of SPIONs were 56 nm and -49 mV,
      respectively. The hydrodynamic and aerodynamic NIM diameters were 1.6 MUm and
      3.27+/-1.69 MUm, respectively. SEM micrographs reveal spherical particles with
      rough surface morphology. TEM and focused ion beam-SEM micrographs corroborate
      the porous nature of NIMs, and surface localization of SPIONs. An in vitro
      tracheal mimic study demonstrates more than twice the spatial deposition and
      retention of NIMs, compared to a liquid suspension, in regions under the
      influence of a strong magnetic gradient. We report the novel formulation of an
      inhaled and magnetically responsive NIM drug delivery vehicle. This vehicle is
      capable of being loaded with one or more chemotherapeutic agents, with future
      translational ability to be targeted to lung tumors using an external magnetic
      field.

PMID- 23964798
TI  - TTFV-based molecular tweezers and macrocycles as receptors for fullerenes.
AB  - Hybrids of tetrathiafulvalene vinylogues (TTFVs) and planar arenes were
      synthesized via the click reaction to form tweezer-like and macrocyclic
      structures. These compounds were investigated as receptors for fullerenes (C60
      and C70) by UV-vis absorption and fluorescence spectroscopy. 

PMID- 23964797
TI  - Etiology and outcomes of acute kidney injury in Chinese children: a prospective
      multicentre investigation.
AB  - BACKGROUND: The incidence of AKI appears to have increasing trend. Up to now,
      prospective, multi-center, large-sample epidemiological study done on pediatric
      AKI on aspects of epidemiological characteristics, causes and outcomes have not
      reported. It is necessary to develop prospective, multi-center, large-sample
      epidemiological study in our country on pediatric AKI. The aim of this study was
      to determine the clinical features, etiology, and outcomes of acute kidney injury
      (AKI) in Chinese children. METHOD: Paediatric patients (<=18 years old) admitted
      to 27 hospitals (14 children's hospitals and 13 general hospitals) affiliated
      with the Medical University were investigated. AKI was defined using the 2005
      Acute Kidney Injury Network criteria. RESULTS: During the study period, 388,736
      paediatric patients were admitted. From this total, AKI was diagnosed in 1,257
      patients, 43 of whom died. The incidence and mortality of AKI was 0.32% and 3.4%
      respectively. The mean (+/- SD) age of patients was 48.4 +/- 50.4 months. Among
      the 1,257 AKI paediatric patients, 632 were less than one year old. Among the AKI
      paediatric patients, 615 (48.9%) were in stage 1, 277 (22.0%) in stage 2, and 365
      (29.0%) in stage 3. The most common causes of AKI were renal causes (57.52%),
      whereas postrenal (25.69%) and prerenal (14.96%) causes were the least common.
      The three most common causes of AKI according to individual etiological disease
      were urolithiasis (22.35%), of which exposure to melamine-contaminated milk
      accounted for the highest incidence (63.7%); acute glomerulonephritis (10.10%);
      and severe dehydration (7.48%). A total of 43 AKI patients (3.4%) died during
      their hospital stay; 15 (34.9%) of the 43 died as a result of sepsis. CONCLUSION:
      Primary renal diseases are a major risk factor for paediatric AKI in China. In
      terms of specific etiological disease, urolithiasis (postrenal disease) was the
      leading cause of paediatric AKI in 2008, when the disease was linked to exposure
      to melamine-contaminated milk. Sepsis is the leading cause of death in Chinese
      paediatric AKI patients. Future studies should focus on effective ways of
      controlling renal disorders and sepsis to improve the clinical management of
      paediatric AKI in China.

PMID- 23964799
TI  - Hyperbaric biofilms on engineering surfaces formed in the deep sea.
AB  - Biofouling is a major problem for long-term deployment of sensors in the marine
      environment. This study showed that significant biofilm formation occurred on a
      variety of artificial materials (glass, copper, Delrin(TM) and poly-methyl
      methacrylate [PMMA]) deployed for 10 days at a depth of 4700 m in the Cayman
      Trough. Biofilm surface coverage was used as an indicator of biomass. The lowest
      biofilm coverage was on copper and PMMA. Molecular analyses indicated that
      bacteria dominated the biofilms found on copper, Delrin(TM) and PMMA with 75, 55
      and 73% coverage, respectively. Archea (66%) were dominant on the glass surface
      simulating interior sensor conditions, whereas Eukarya comprised the highest
      percentage of microflora (75%) on the glass simulating the exterior of sensors.
      Analysis of Denaturing Gradient Gel Electrophoresis profiles indicated that
      copper and Delrin(TM) shared the same community diversity, which was not the case
      for glass and PMMA, or between PMMA and copper/Delrin(TM). Sequence alignment
      matches belonged exclusively to uncultivable microorganisms, most of which were
      not further classified. One extracted sequence found on glass was associated with
      Cowellia sp., while another extracted from the PMMA surface was associated with a
      bacterium in the Alterominidaceae, both gamma-proteobacteria. The results
      demonstrate the necessity of understanding biofilm formation in the deep sea and
      the potential need for mitigation strategies for any kind of long-term deployment
      of remote sensors in the marine environment. 

PMID- 23964801
TI  - Face-selective cells in the temporal cortex of monkeys.
AB  - The notion of a neuron that responds selectively to the image of a particular
      complex object has been controversial ever since Gross and his colleagues
      reported neurons in the temporal cortex of monkeys that were selective for the
      sight of a monkey's hand (Gross, Rocha-Miranda, & Bender, 1972). Since that time,
      evidence has mounted for neurons in the temporal lobe that respond selectively to
      faces. The present paper presents a critical analysis of the evidence for face
      neurons and discusses the implications of these neurons for models of object
      recognition. The paper also presents some possible reasons for the evolution of
      face neurons and suggests some analogies with the development of language in
      humans. 

PMID- 23964800
TI  - Association of gut microbiota with post-operative clinical course in Crohn's
      disease.
AB  - BACKGROUND: The gut microbiome is altered in Crohn's disease. Although individual
      taxa have been correlated with post-operative clinical course, global trends in
      microbial diversity have not been described in this context. METHODS: We
      collected mucosal biopsies from the terminal ileum and ascending colon during
      surgery and post-operative colonoscopy in 6 Crohn's patients undergoing ileocolic
      resection (and 40 additional Crohn's and healthy control patients undergoing
      either surgery or colonoscopy). Using next-generation sequencing technology, we
      profiled the gut microbiota in order to identify changes associated with
      remission or recurrence of inflammation. RESULTS: We performed 16S ribosomal
      profiling using 101 base-pair single-end sequencing on the Illumina GAIIx
      platform with deep coverage, at an average depth of 1.3 million high quality
      reads per sample. At the time of surgery, Crohn's patients who would remain in
      remission were more similar to controls and more species-rich than Crohn's
      patients with subsequent recurrence. Patients remaining in remission also
      exhibited greater stability of the microbiota through time. CONCLUSIONS: These
      observations permitted an association of gut microbial profiles with probability
      of recurrence in this limited single-center study. These results suggest that
      profiling the gut microbiota may be useful in guiding treatment of Crohn's
      patients undergoing surgery.

PMID- 23964802
TI  - Visual processing of faces in temporal cortex: physiological evidence for a
      modular organization and possible anatomical correlates.
AB  - Physiological recordings along the length of the upper bank of the superior
      temporal sulcus (STS) revealed cells each of which was selectively responsive to
      a particular view of the head and body. Such cells were grouped in large patches
      3-4 mm across. The patches were separated by regions of cortex containing cells
      responsive to other stimuli. The distribution of cells projecting from temporal
      cortex to the posterior regions of the inferior parietal lobe was studied with
      retrogradely transported fluorescent dyes. A strong temporoparietal projection
      was found originating from the upper bank of the STS. Cells projecting to the
      parietal cortex occurred in large patches or bands. The size and periodicity of
      modules defined through anatomical connections matched the functional
      subdivisions of the STS cortex involved in face processing evident in
      physiological recordings. It is speculated that the temporoparietal projections
      could provide a route through which temporal lobe analysis of facial signals
      about the direction of others' attention can be passed to parietal systems
      concerned with spatial awareness. 

PMID- 23964803
TI  - Can we lose memories of faces? Content specificity and awareness in a
      prosopagnosic.
AB  - Prosopagnosia is a neurological syndrome in which patients cannot recognize
      faces. Kecently it has been shown that some prosopagnosics give evidence of
      "covert" recognition: they show greater autonomic responses to familiar faces
      than to unfamiliar ones, and respond differently to familiar faces in learning
      and interference tasks. Although some patients do not show covert recognition,
      this has usually been attributed to an "apperceptive" deficit that impairs
      perceptual analysis of the input. The implication is that prosopagnosia is a
      deficit in access to, or awareness of, memories of faces: the inducing brain
      injury does not destroy the memories themselves. We present a case study that
      challenges this view. LH suffers from prosopagnosia as the result of a closed
      head injury. He cannot recognize familiar faces or report that they are familiar,
      nor answer questions about the faces from memory, though he can (1) recognize
      common objects and subtly varying shapes, (2) match faces while ignoring
      irrelevant information such as emotional expression or angle of view, (3)
      recognize sex, age, and like-ability from faces, and (4) recognize people by a
      number of nonfacial channels. The only other categories of shapes that he has
      marked trouble recognizing are animals and emotional expressions, though even
      these impairments were not as severe as the one for faces. Three measures
      (sympathetic skin response, pupil dilation, and learning correct and incorrect
      names of faces) failed to show any signs of covert face recognition in LH, though
      the measures were sensitive enough to reflect autonomic reactions in LH to
      stimuli other than faces, and face familiarity in normal controls. Thus
      prosopagnosia cannot always be attributed to a mere absence of awareness (i.e.,
      preserved information about faces whose output is disconnected from conscious
      cognitive processing), to an apperceptive deficit (i.e., preserved information
      about faces that cannot be accessed due to improperly analyzed perceptual input),
      or to an inability to recognize complex or subtly varying shapes (i.e., loss or
      degradation of shape memory in general). We conclude that it is possible for
      brain injury to eliminate the storage of information about familiar faces and
      certain related shapes. 

PMID- 23964804
TI  - Separable mechanisms in face processing: evidence from hemispheric
      specialization.
AB  - This article addresses three issues in face processing: First, is face processing
      primarily accomplished by the right hemisphere, or do both left- and right
      hemisphere mechanisms play important roles? Second, are the mechanisms the same
      as those involved in general visual processing, or are they dedicated to face
      processing? Third, how can the mechanisms be characterized more precisely in
      terms of processes such as visual parsing? We explored these issues using the
      divided visual field methodology in four experiments. Experiments 1 and 2
      provided evidence that both left- and right-hemisphere mechanisms are involved in
      face processing. In Experiment 1, a right-hemisphere advantage was found for both
      Same and Different trials when Same faces were identical and Different faces
      differed on all three internal facial features. Experiment 2 replicated the right
      hemisphere advantage for Same trials but showed a left-hemisphere advantage for
      Different trials when one of three facial features differed between the target
      and the probe faces. Experiment 3 showed that the right-hemisphere advantage
      obtained with upright faces in Experiment 2 disappeared when the faces were
      inverted. This result suggests that there are right-hemisphere mechanisms
      specialized for processing upright faces, although it could not be determined
      whether these mechanisms are completely face-specific. Experiment 3 also provided
      evidence that the left-hemisphere mechanisms utilized in face processing tasks
      are general-purpose visual mechanisms not restricted to particular classes of
      visual stimuli. In Experiment 4, a left-hemisphere advantage was obtained when
      the task was to find one facial feature that was the same between the target and
      the probe faces. We suggest that left-hemisphere advantages shown in face
      processing are due to the parsing and analysis of the local elements of a face. 

PMID- 23964805
TI  - Deformable templates for face recognition.
AB  - We describe an approach for extracting facial features from images and for
      determining the spatial organization between these features using the concept of
      a deformable template. This is a parameterized geometric model of the object to
      be recognized together with a measure of how well it fits the image data.
      Variations in the parameters correspond to allowable deformations of the object
      and can be specified by a probabilistic model. After the extraction stage the
      parameters of the deformable template can be used for object description and
      recognition. 

PMID- 23964806
TI  - Eigenfaces for recognition.
AB  - We have developed a near-real-time computer system that can locate and track a
      subject's head, and then recognize the person by comparing characteristics of the
      face to those of known individuals. The computational approach taken in this
      system is motivated by both physiology and information theory, as well as by the
      practical requirements of near-real-time performance and accuracy. Our approach
      treats the face recognition problem as an intrinsically two-dimensional (2-D)
      recognition problem rather than requiring recovery of three-dimensional geometry,
      taking advantage of the fact that faces are normally upright and thus may be
      described by a small set of 2-D characteristic views. The system functions by
      projecting face images onto a feature space that spans the significant variations
      among known face images. The significant features are known as "eigenfaces,"
      because they are the eigenvectors (principal components) of the set of faces;
      they do not necessarily correspond to features such as eyes, ears, and noses. The
      projection operation characterizes an individual face by a weighted sum of the
      eigenface features, and so to recognize a particular face it is necessary only to
      compare these weights to those of known individuals. Some particular advantages
      of our approach are that it provides for the ability to learn and later recognize
      new faces in an unsupervised manner, and that it is easy to implement using a
      neural network architecture. 

PMID- 23964807
TI  - Parameterizing exemplars of categories.

PMID- 23964809
TI  - Preface.

PMID- 23964808
TI  - Interview with endel tulving.

PMID- 23964810
TI  - The effect of antiobesity drugs on waist circumference: a mixed treatment
      comparison.
AB  - AIM: To use meta-analytic techniques to quantitatively evaluate the efficacy of
      orlistat and lorcaserin in the treatment of people who are overweight and obese.
      METHODS: We identified publications from searches of electronic databases and
      extracted data from studies that compared orlistat or lorcaserin to lifestyle
      advice (standard care), placebo, sibutramine, rimonabant or metformin and
      collected information on waist circumference change or withdrawals due to adverse
      events (AEs). A mixed treatment comparison (MTC) meta-analysis was performed on
      the data extracted. RESULTS: Orlistat was found to be significantly better than
      placebo and standard care in reducing waist circumference at 6 and 12 months;
      orlistat reduced waist circumference by -6.96 cm [95% credible interval (CrI): 
      8.93, -4.96 cm] compared to standard care at 6 months. The results suggested that
      lorcaserin reduced waist circumference by a greater amount than all other
      interventions at 12 months, for example, lorcaserin lead to a greater reduction
      of -2.45 cm (95% CrI: -4.99, 0.08 cm) in comparison to placebo, although these
      differences were not statistically significant. Although data were very limited,
      metformin reduced waist circumference by a greater amount (-2.11 cm, 95% CI: 
      1.00, -3.22 cm) than orlistat at 6 months. On average, 6.5% of patients on
      orlistat and 5.4% of those on lorcaserin discontinued their treatment due to AEs
      at 12 months. CONCLUSIONS: Orlistat should be considered as an addition to
      lifestyle interventions in the treatment of obesity. Lorcaserin has recently been
      approved by the US Food and Drug Administration (FDA) and these results suggest
      that it is similar in both efficacy and safety compared to orlistat.

PMID- 23964811
TI  - Does shape co-variation between the skull and the mandible have functional
      consequences? A 3D approach for a 3D problem.
AB  - Morpho-functional patterns are important drivers of phenotypic diversity given
      their importance in a fitness-related context. Although modularity of the
      mandible and skull has been studied extensively in mammals, few studies have
      explored shape co-variation between these two structures. Despite being
      developmentally independent, the skull and mandible form a functionally
      integrated unit. In the present paper we use 3D surface geometric morphometric
      methods allowing us to explore the form of both skull and mandible in its 3D
      complexity using the greater white-toothed shrew as a model. This approach allows
      an accurate 3D description of zones devoid of anatomical landmarks that are
      functionally important. Two-block partial least-squares approaches were used to
      describe the co-variation of form between skull and mandible. Moreover, a 3D
      biomechanical model was used to explore the functional consequences of the
      observed patterns of co-variation. Our results show the efficiency of the method
      in investigations of complex morpho-functional patterns. Indeed, the description
      of shape co-variation between the skull and the mandible highlighted the location
      and the intensity of their functional relationships through the jaw adductor
      muscles linking these two structures. Our results also demonstrated that shape co
      variation in form between the skull and mandible has direct functional
      consequences on the recruitment of muscles during biting. 

PMID- 23964813
TI  - The impact of mentalization training on the reflective function of novice
      therapists: a randomized controlled trial.
AB  - This study examined whether training can increase the reflective function (RF) of
      novice therapists about patients with Borderline Personality Disorder (BPD). A
      total of 48 students in clinical psychology were randomly assigned to
      mentalization training or didactic training. Their RF regarding patients was
      assessed with the Therapist Mental Activity Scale (TMAS: Normandin, Ensink, &
      Maheux, 2012). The RF of trainees assigned to the mentalization training improved
      significantly, while participants who received traditional didactic training
      actually became significantly less reflective. These findings show that brief
      mentalization training can help beginner therapists develop their mentalization
      capacities with challenging patients.

PMID- 23964814
TI  - What else are psychotherapy trainees learning? A qualitative model of students'
      personal experiences based on two populations.
AB  - After an introductory course in experiential-integrative psychotherapy, 21
      graduate students provided personal narratives of their experiences, which were
      analyzed using the grounded theory method. Results produced 37 hierarchically
      organized experiences, revealing that students perceived multiple changes in both
      professional (i.e., skill acquisition and learning related to the therapeutic
      process) and personal (i.e., self growth in a more private sphere) domains.
      Analysis also highlighted key areas of difficulties in training. By adding the
      personal accounts of graduate trainees, this study enriches and extends Pascual
      Leone et al.'s (2012) findings on undergraduates' experiences, raising the number
      of cases represented in the model to 45. Findings confirm the model of novice
      trainee experiences while highlighting the unique experiences of undergraduate
      vs. graduate trainees.

PMID- 23964815
TI  - Radical-radical interactions among oxidized guanine bases including guanine
      radical cation and dehydrogenated guanine radicals.
AB  - We present here a theoretical investigation of the structural and electronic
      properties of di-ionized GG base pairs (G(*+)G(*+),G(-H1)(*)G(*+), and G(
      H1)(*)G(-H1)(*)) consisting of the guanine cation radical (G(*+)) and/or
      dehydrogenated guanine radical (G(-H1)(*)) using density functional theory
      calculations. Different coupling modes (Watson-Crick/WC, Hoogsteen/Hoog, and
      minor groove/min hydrogen bonding, and pi-pi stacking modes) are considered. We
      infer that a series of G(*+)G(*+) complexes can be formed by the high-energy
      radiation. On the basis of density functional theory and complete active space
      self-consistent (CASSCF) calculations, we reveal that in the H-bonded and N-N
      cross-linked modes, (G(*+)G(*+))WC, (G(-H1)(*)G(-H1)(*))WC, (G(-H1)(*)G(
      H1)(*))minI, and (G(-H1)(*)G(-H1)(*))minIII have the triplet ground states;
      (G(*+)G(*+))HoogI, (G(-H1)(*)G(*+))WC, (G(-H1)(*)G(*+))HoogI, (G(
      H1)(*)G(*+))minI, (G(-H1)(*)G(*+))minII, and (G(-H1)(*)G(-H1)(*))minII possess
      open-shell broken-symmetry diradical-characterized singlet ground states; and
      (G(*+)G(*+))HoogII, (G(*+)G(*+))minI, (G(*+)G(*+))minII, (G(*+)G(*+))minIII,
      (G(*+)G(*+))HoHo, (G(-H1)(*)G(*+))minIII, (G(-H1)(*)G(*+))HoHo, and (G(-H1)(*)G(
      H1)(*))HoHo are the closed-shell systems. For these H-bonded diradical complexes,
      the magnetic interactions are weak, especially in the diradical G(*+)G(*+) series
      and G(-H1)(*)G(-H1)(*) series. The magnetic coupling interactions of the
      diradical systems are controlled by intermolecular interactions (H-bond,
      electrostatic repulsion, and radical coupling). The radical-radical interaction
      in the pi-pi stacked di-ionized GG base pairs ((G(*+)G(*+))pipi, (G(
      H1)(*)G(*+))pipi, and (G(-H1)(*)G(-H1)(*))pipi) are also considered, and the
      magnetic coupling interactions in these pi-pi stacked base pairs are large. This
      is the first theoretical prediction that some di-ionized GG base pairs possess
      diradical characters with variable degrees of ferromagnetic and antiferromagnetic
      characteristics, depending on the dehydrogenation characters of the bases and
      their interaction modes. Hopefully, this work provides some helpful information
      for the understanding of different structures and properties of the di-ionized GG
      base pairs. 

PMID- 23964816
TI  - Retroelement insertions at the Medicago FTa1 locus in spring mutants eliminate
      vernalisation but not long-day requirements for early flowering.
AB  - Molecular-genetic control of the flowering time of temperate-climate plants is
      best understood in Arabidopsis and the cereals wheat and barley. However, key
      regulators such as FLC and cereal VRN2 are not found in legumes. Therefore, we
      used forward genetics to identify flowering time genes in the model legume
      Medicago truncatula (Medicago) which is induced to flower by vernalisation and
      long-day photoperiods. A screen of a Tnt1 retroelement tagging population yielded
      two mutants, spring2 and spring3, with a dominant early flowering phenotype.
      These mutants overexpress the floral activator FTa1 and two candidate downstream
      flowering genes SOC1a and FULb, similar to the spring1 somaclonal variant that we
      identified previously. We demonstrate here that an increase in the expression of
      FTa1, SOC1a and FULb and early flowering does not occur in all conditions in the
      spring mutants. It depends on long-day photoperiods but not on vernalisation.
      Isolation of flanking sequence tags and linkage analysis identified retroelement
      insertions at FTa1 that co-segregated with the early flowering phenotype in all
      three spring mutants. These were Tnt1 insertions in the FTa1 third intron
      (spring3) or the 3' intergenic region (spring2) and an endogenous MERE1-4
      retroelement in the 3' intergenic region in spring1. Thus the spring mutants form
      an allelic series of gain-of-function mutations in FTa1 which confer a spring
      growth habit. The spring retroelement insertions at FTa1 separate long-day input
      from vernalisation input into FTa1 regulation, but this is not due to large-scale
      changes in FTa1 DNA methylation or transcript processing in the mutants. 

PMID- 23964817
TI  - Evaluation of the oral direct factor Xa inhibitor - betrixaban.
AB  - INTRODUCTION: For over 60 years vitamin K antagonists have been the mainstay of
      oral therapy for treatment and prevention of venous and arterial thromboembolic
      disease. The emergence of two new classes of orally administered anticoagulants,
      direct thrombin and factor Xa inhibitors have drastically changed the landscape
      in the management of these disease states. Betrixaban , an orally administered
      direct factor Xa inhibitor, is entering a Phase III trial and undergoing
      investigation for similar indications as apixaban, dabigatran and rivaroxaban.
      AREAS COVERED: The chemical development of betrixaban, pharmacokinetic
      differences between betrixaban and currently available novel anticoagulants and
      future considerations for clinical use. EXPERT OPINION: Betrixaban, the fifth
      novel oral anticoagulant in line for the Food and Drug Administration (FDA)
      approval, possesses some unique pharmacokinetic characteristics in comparison
      with the currently available novel anticoagulants, including limited renal
      excretion, minimal metabolism through the cytochrome p450 system and a long half
      life. This pharmacokinetic profile may allow greater flexibility for use in
      patients with poor renal function, offer the convenience of once daily dosing,
      and exhibit less drug interactions. Betrixaban is currently being evaluated for
      prophylaxis against venous thromboembolic disease (VTED) and the prevention of
      stroke and systemic embolism associated with nonvalvular atrial fibrillation, its
      role in the management of acute VTED and acute coronary syndromes is yet to be
      defined based on clinical data and evaluation. Of interest, a factor Xa decoy,
      PRT4445, is currently under evaluation in conjunction with betrixaban, and may be
      a universal reversal agent for all anticoagulants with anti-Xa activity.
      Currently, there are no specific reversal agents for the novel anticoagulants.
      The availability of an effective reversal agent would be very attractive for the
      management of associated bleeding, bleeding due to trauma, or the need for
      emergent surgery.

PMID- 23964818
TI  - Prognostic significance of immunoglobulin M overexpression in laryngeal squamous
      cell carcinoma.
AB  - CONCLUSIONS: Immunoglobulin (Ig) M is overexpressed in laryngeal squamous cell
      carcinoma (LSCC), and its expression has an independent protective impact on
      disease-free survival in LSCC. OBJECTIVE: A number of studies have reported on
      the ectopic expression of Ig in cancer cells, yet there has been a lack of
      understanding of its clinical and prognostic significance. This study aimed to
      investigate the expression of IgM in resected specimens of LSCC and to evaluate
      its clinical significance and prognostic value. METHODS: Immunohistochemistry
      (IHC) and Western blotting were used to detect the expression of IgM in LSCC and
      normal laryngeal tissues. The serum level of IgM was also analyzed by
      immunoturbidimetric assay. RESULTS: IHC and Western blot studies demonstrated
      that IgM was overexpressed in LSCC specimens (p < 0.001), while the serum level
      of IgM in patients with LSCC was not different from healthy controls. Chi-squared
      analysis revealed that the expression level of IgM was negatively correlated with
      regional lymph node metastasis and tumor stage (p = 0.011 and 0.025,
      respectively). Univariate analysis showed that IgM expression was significantly
      correlated with enhanced disease-free survival (DFS) (p = 0.004). In multivariate
      analysis, IgM retained its independent prognostic value for DFS (p = 0.048, HR =
      0.506, 95% CI = 0.257-0.995).

PMID- 23964819
TI  - Rotational study of cis- and trans-acrylic acid-trifluoroacetic acid.
AB  - The rotational spectra of the normal and deuterated species of the acrylic acid
      trifluoroacetic acid complex have been assigned for both cis and trans
      conformations with the pulsed jet Fourier transform microwave technique. Relative
      intensity measurements suggest that the cis species is more stable than the trans
      one, in agreement with the ab initio results. The deuteration of the carboxylic
      groups generates an increase of the distance between the two moieties of the
      complex (Ubbelohde effect) and prevents the possibility of locating the OH
      hydrogen atoms. The changes of the Paa planar moment of inertia upon OH -> OD
      substitution allowed for a quantitative estimate of the Ubbelohde effect. 

PMID- 23964821
TI  - Primary chondrosarcoma of the breast: a case presentation and review of the
      literature.
AB  - Mammary sarcomas are uncommon tumors. When tumors like malignant
      cystosarcomaphyllodes and metaplastic carcinoma, where malignant cartilaginous
      areas may be present, are excluded, only nine cases have been reported to date.We
      report another case of primary chondrosarcoma of the breast here. A 24-year-old
      Mediterranean woman presented with a painful mass in the right breast and a
      physical examination revealed a palpable mass. An incisional biopsy was performed
      and primary chondrosarcoma was diagnosed based on histological examination. Our
      patient underwent a mastectomy. A preoperative clinical and cytological diagnosis
      of chondrosarcoma, even though possible in a few cases, is usually not attained
      due to its similar clinical behavior with other breast tumors.

PMID- 23964822
TI  - Carbon/ternary alloy/carbon optical stack on mylar as an optical data storage
      medium to potentially replace magnetic tape.
AB  - A novel write-once-read-many (WORM) optical stack on Mylar tape is proposed as a
      replacement for magnetic tape for archival data storage. This optical tape
      contains a cosputtered bismuth-tellurium-selenium (BTS) alloy as the write layer
      sandwiched between thin, protective films of reactively sputtered carbon. The
      composition and thickness of the BTS layer were confirmed by Rutherford
      Backscattering (RBS) and atomic force microscopy (AFM), respectively. The C/BTS/C
      stack on Mylar was written to/marked by 532 nm laser pulses. Under the same
      conditions, control Mylar films without the optical stack were unaffected. Marks,
      which showed craters/movement of the write material, were characterized by
      optical microscopy and AFM. The threshold laser powers for making marks on
      C/BTS/C stacks with different thicknesses were explored. Higher quality marks
      were made with a 60* objective compared to a 40* objective in our marking
      apparatus. The laser writing process was simulated with COMSOL. 

PMID- 23964823
TI  - Novel mixed-ligand copper(I) complexes: role of diimine ligands on cytotoxicity
      and genotoxicity.
AB  - Novel tetrahedral copper(I) mixed-ligand complexes of the type
      [Cu(X)(N(?)N)(PCN)], 3-10, where X = Cl or Br, N(?)N = 2,2'-bipyridine (bipy),
      1,10-phenanthroline (phen), 5,6-dimethyl-1,10-phenanthroline (dmp), and dipyrido
      [3,2-d:2',3'-f]-quinoxaline (dpq), and PCN = tris-(2-cyanoethyl)phosphine, have
      been synthetized and characterized by NMR, ESI-MS, and X-ray diffraction on two
      representative examples, [CuCl(phen)(PCN)].DMF (5.DMF) and [CuBr(dpq)(PCN)].2DMF
      (10.2DMF). Cu(I) complexes were evaluated for their in vitro antitumor properties
      against a panel of human cancer cell lines, including cisplatin- and multidrug
      resistant sublines. The most effective complex, [CuCl(dpq)(PCN)] (9), exhibited
      nanomolar cytotoxicity toward both sensitive and resistant cancer cells, but it
      significantly inhibited the growth of cultured normal cells. In vitro DNA assays
      and single cell gel electrophoresis revealed that 9 induced DNA fragmentation
      resulting in cell apoptosis. In parallel, fluorescence in situ hybridization
      (FISH) micronucleus assay attested high levels of genotoxicity following
      treatment of peripheral blood lymphocytes with complex 9, suggesting that the
      potential risk posed by diimine metal complexes should be carefully reconsidered.

PMID- 23964824
TI  - Isotope labeling studies on the electron impact mass spectral fragmentation
      patterns of chloropropanol acetates.
AB  - Chloropropanol (CP) esters are part of an emerging group of process-induced
      toxicants that are considered as potential health hazards particularly in palm
      oil. Mass spectrometry-based methodologies for identification of CP esters in
      food are critical in overcoming the challenges associated with direct detection
      methods. In the present study, a convenient strategy was employed to generate all
      possible CP acetates through reacting acetic anhydride with either glycerol in
      the presence of a chloride source or the corresponding CPs, such as 3-chloro-,
      1,3-dichloro-, 2-chloro-, and 1,2-dichloropropanols, allowing for the
      identification of the individual CP acetates and assignment of their mass
      spectral fragmentations. Mass spectral fragmentations were confirmed through the
      use of the isotopic signature of chlorine in addition to the isotope labeling
      experiments performed using isotopically labeled precursors, such as [13C-U3]
      glycerol, [13C-U4] acetic anhydride, [13C-2,2'] acetic anhydride, and [d5] 3
      monochloropropane-1,2-diol (3-MCPD) as reactants. Such studies have indicated
      that all CP esters can undergo two general fragmentations under electron impact
      (EI) conditions, one generating the acylium ion at m/z 45 and the other
      generating a chlorinated cyclic acyloxonium ion at m/z 135.6. Considering the
      fact that such ions can also be generated from any fatty acid containing CP
      esters after undergoing McLafferty rearrangement, the ion at m/z 135.6 can
      therefore be considered as a universal marker for the presence of CP esters
      undergoing EI fragmentation. Furthermore, these studies have also indicated the
      formation of ions characteristic of CP diesters, monoesters, and dichloro esters.

PMID- 23964825
TI  - Children's misunderstandings of hazard warning signs in the new globally
      harmonized system for classification and labeling.
AB  - Accidental chemical poisoning causes more than 35 000 child deaths every year
      across the world, and it leads to disease, disability, and suffering for many
      more children. Children's ignorance of dangers and their failure to interpret
      hazard warning signs as intended contribute significantly to this problem. A new
      Globally Harmonized System for Classification and Labeling is being implemented
      internationally with a view to unifying the current multiple and disparate
      national systems. This study was designed to establish a productive, effective
      means of teaching the new GHS warning signs to primary school children (aged 7-11
      years). A pre-test, post-test, follow-up test design was employed, with a
      teaching intervention informed by a Delphi survey of expert opinion. Children
      from one school formed the experimental group (n = 49) and a second school
      provided a control group (n = 23). Both groups showed a gain in knowledge from
      pre-test to post-test, the experimental group with a larger gain but which was
      not statistically significant. However, longer-term retention of knowledge, as
      shown by the follow-up test, was statistically significantly greater in the
      experimental group (p = 0.001). The employment of teaching to match children's
      preferred learning styles, and the use of active learning were found to be
      related to improved retention of knowledge. Part of the study involved eliciting
      children's interpretation of standard hazard warning symbols, and this provoked
      considerable concern over the potential for dangerous misinterpretation with
      disastrous consequences. This article focuses on the reasons for such
      misconception and the action required to address this successfully in testing the
      intervention. 

PMID- 23964826
TI  - Pediatric pressure injuries: does modifying a tool alter the risk assessment
      outcome?
AB  - The aim of this study was to determine whether assessing patient risk of
      developing pressure injuries in Pediatric Intensive Care (PICU) and Neonatal
      Units (NNU) using a modification of the Glamorgan Scale (mGS) would alter the
      risk identification when compared to the Glamorgan Scale (GS). Prospective data
      were collected from a convenience sample of patients admitted to PICU or NNU
      during a 2-month period. The patients' pressure injury risk score using both
      instruments was collected by observing patients, reviewing patient records, and
      clarifying information with bedside nurses. Chi square analysis was used to
      compare the risk category allocations. A total of 133 patients were assessed with
      complete data available for 112 (PICU = 68, NNU = 65). The total number of
      admissions during the data collection period was 202 in PICU and 100 in NNU.
      There was an extensive spread of patients allocated to the "High Risk" and "Very
      High Risk" categories in both units. Only one was in the lower "At Risk"
      category. There was little difference in allocated risk category between the mGS
      and the GS (p = 0.982). Only one patient was not allocated to the same risk
      category by both tools. In addition to identifying little difference in risk
      identification the mGS was found to be easier to complete. The mGS delivered the
      same risk rating as the GS when applied to patients in the PICU and NNU. It is
      not clear if a similar agreement exists in the general pediatric population. When
      modifying a validated tool for local use consideration should be given as to how
      those modifications might alter outcomes. 

PMID- 23964827
TI  - Increased visfatin in hemodialysis patients is associated with decreased demands
      for recombinant human erythropoietin.
AB  - BACKGROUND: Studies detected an association between visfatin and markers of iron
      metabolism in patients with insulin resistance. In this study, such a relation
      was evaluated in hemodialysis (HD) patients. Also relations between visfatin and
      hepcidin, demands for recombinant human erythropoietin (rHuEpo), inflammation,
      and situations characterized by insulin resistance were evaluated. METHODS: After
      a four-week washout period from iron treatment, 33 HD patients and 20 healthy
      volunteers enrolled in the study. Serum visfatin, hepcidin, and interleukin-6 (IL
      6) were assessed by means of enzyme-linked immunosorbent assay. Hemoglobin, serum
      iron, ferritin, and transferrin saturation (TSAT) were also measured. RESULTS:
      Visfatin was markedly increased in HD patients. Visfatin levels did not differ
      between diabetics and non-diabetics. No relation was detected between visfatin
      and body mass index or IL-6 in HD patients. From the markers of iron metabolism,
      the hepcidin included, visfatin was related only to TSAT. A strong positive
      relation was revealed between visfatin and hemoglobin, whereas visfatin was
      inversely related to rHuEpo dose. Resistance to rHuEpo index was inversely and
      independently of TSAT related to visfatin. CONCLUSION: Visfatin is increased in
      HD patients and it is associated with decreased demands for rHuEpo.

PMID- 23964828
TI  - Antifungal susceptibilities and identification of species of the Sporothrix
      schenckii complex isolated in Brazil.
AB  - Sporotrichosis is a subacute or chronic mycosis caused worldwide by the dimorphic
      species complex, Sporothrix schenckii. We studied 85 isolates recovered in Brazil
      to verify their identification and evaluate their in vitro antifungal
      susceptibility patterns. Based on phenotypic tests (microscopic features, ability
      to grow at 30 degrees C and 37 degrees C, colony diameters, as well as
      assimilation of sucrose and raffinose) and molecular assays (amplification of a
      fragment of the calmodulin gene), the strains were identified as S. schenckii, S.
      brasiliensis and S. globosa, with a predominance of S. schenckii isolates. There
      was 37.7% disagreement between the phenotypic and genotypic identification
      methodologies. In general, terbinafine was the most active drug, followed by
      ketoconazole and itraconazole, and the less active fluconazole and voriconazole.
      Five isolates (one S. globosa and four S. schenckii) were found to be
      itraconazole-resistant strains but, in general, there were no differences in the
      in vitro antifungal susceptibility profiles among the Sporothrix species. 

PMID- 23964829
TI  - Pneumocystis jirovecii haplotypes at the internal transcribed spacers of the rRNA
      operon in French HIV-negative patients with diverse clinical presentations of
      Pneumocystis infections.
AB  - Pneumocystis jirovecii, a transmissible fungus, is the causative agent of
      pulmonary infections. Its genomic diversity has appeared in reports from around
      the world but data on P. jirovecii genotypes in France are still limited. This
      study describes the typing of P. jirovecii isolates from 81 HIV-negative patients
      monitored at Brest University Hospital, Brittany, France, 40 of whom developed
      Pneumocystis pneumonia (PcP), and remaining 41 patients were colonized by the
      fungus. The isolates were assayed at the internal transcribed spacer (ITS)1 and
      ITS2 under improved amplification conditions to avoid in vitro ITS recombination.
      P. jirovecii ITS haplotypes were identified in 56/81 patients (31 PcP patients
      and 25 patients who were colonized) which revealed a high diversity in that 27
      different haplotypes were identified. Eg was the most frequent haplotype (31/56,
      55.3%), followed by Ec and Ai (5/56, 8.9% each). In contrast, Ne, usually the
      second most frequent haplotype in Europe and the USA, was observed in only 2/56
      patients (3.6%). Mixed infections were detected in 18/56 patients (32.1%; 12 PcP
      patients and six who were colonized). No significant differences were observed in
      haplotype diversity, frequency of peculiar haplotypes, and mixed infection
      occurrence, between the two patient populations. The study, conducted with the
      largest HIV-negative patient population investigated so far, shows that ITS
      typing remains an efficient method for characterizing P. jirovecii among human
      populations, whatever their clinical presentation of Pneumocystis infections.

PMID- 23964830
TI  - Effect of tadalafil and 3-hydroxy-3-methylglutaryl coenzyme A inhibitor statin on
      the haemodynamics of cavernous and brachial arteries.
AB  - Erectile dysfunction (ED) is usually associated with cardiovascular disease and
      reduced endothelial function. The aim of the present study was to examine the
      effect of tadalafil and statin on the endothelial function of cavernous and
      brachial arteries in healthy men and in patients with ED. The cases included in
      the study were as follows: 150 men with ED complaints for at least 6 months, and
      50 healthy volunteers without sexual problems. Patients were randomly divided
      into four groups of equal numbers. Group 1 received 20 mg of tadalafil on
      alternate days, Group 2 received 10 mg of statin a day, Group 3 received
      tadalafil on alternate days and 10 mg of statin a day, and the last group served
      as controls. Noninvasive evaluation of brachial artery flow-mediated dilatation
      (FMD) and percentage of increase in cavernosal arteries diameter (PICAD) was
      conducted via ultrasound at baseline and 4 weeks after administration of
      tadalafil or atorvastatin. Before drug administration, FMD and PICAD values did
      not significantly differ among the three treatment groups. After drug
      administration, FMD and PICAD values significantly increased in patients
      receiving tadalafil and tadalafil+statin (P < 0.001), but not in patients
      receiving only statin. These findings suggested that use of tadalafil alone and
      tadalafil combined with statin improved endothelial function of cavernous and
      brachial arteries.

PMID- 23964831
TI  - Potential for the Australian and New Zealand paediatric intensive care registry
      to enhance acute flaccid paralysis surveillance in Australia: a data-linkage
      study.
AB  - BACKGROUND: Australia uses acute flaccid paralysis (AFP) surveillance to monitor
      its polio-free status. The World Health Organization criterion for a sensitive
      AFP surveillance system is the annual detection of at least one non-polio AFP
      case per 100,000 children aged less than 15 years, a target Australia has not
      consistently achieved. Children exhibiting AFP are likely to be hospitalised and
      may be admitted to an intensive care unit. This provides a potential opportunity
      for active AFP surveillance. METHODS: A data-linkage study for the period from 1
      January 2005 to 31 December 2008 compared 165 non-polio AFP cases classified by
      the Polio Expert Panel with 880 acute neurological presentations potentially
      compatible with AFP documented in the Australian and New Zealand Paediatric
      Intensive Care (ANZPIC) Registry. RESULTS: Forty-two (25%) AFP cases classified
      by the Polio Expert Panel were matched to case records in the ANZPIC Registry. Of
      these, nineteen (45%) cases were classified as Guillain-Barre syndrome on both
      registries. Ten additional Guillain-Barre syndrome cases recorded in the ANZPIC
      Registry were not notified to the national AFP surveillance system. CONCLUSIONS:
      The identification of a further ten AFP cases supports inclusion of intensive
      care units in national AFP surveillance, particularly specialist paediatric
      intensive care units, to identify AFP cases that may not otherwise be reported to
      the national surveillance system.

PMID- 23964834
TI  - On the formation of a third, nanostructured domain in ionic liquids.
AB  - The study of solid-fluid transitions in fluorinated ionic liquids using
      differential scanning calorimetry, rheology, and molecular modeling techniques is
      an essential step toward the understanding of their dynamics and the
      thermodynamics and the development of potential applications. Two fluorinated
      ionic liquids were studied: 1-hexyl-3-methylimidazolium perfluorobutanesulfonate,
      HMIm(PFBu)SO3, and tetrabutylammonium perfluorobutanesulfonate, NB4(PFBu)SO3. The
      experimental calorimetric and rheological data were analyzed taking into account
      the possible mesoscale structure of the two fluorinated ionic liquids. The
      simulation results indicate the possible formation of three nanosegregated
      domains-polar, nonpolar, and fluorous-that may have a profound impact on ionic
      liquid research. In the case of HMIm (PFBu)SO3 the three types of mesoscopic
      domains can act as interchangeable jigsaw pieces enabling the formation of
      multiple types of crystals and inducing the observed calorimetry and rheological
      trends. 

PMID- 23964833
TI  - Effect of glycemic control on soluble RAGE and oxidative stress in type 2
      diabetic patients.
AB  - BACKGROUND: The interaction of advanced glycation end products (AGEs) and its
      receptor (RAGE) has played an important role in the pathogenesis of diabetes and
      its complications. A soluble form of RAGE (sRAGE) has been reported as a decoy
      receptor for AGEs. Oxidative stress is demonstrated in pathological condition
      such as atherosclerosis and diabetes mellitus. It has been suggested to be
      involved in the pathogenesis of both macro- and microvascular complications. This
      study was designed to evaluate the effect of glycemic control on sRAGE and
      oxidative stress markers in type 2 diabetic patients. METHODS: Seventy patients
      with type 2 diabetes and 20 healthy subjects were recruited into the study. Blood
      glutathione (GSH) and plasma total nitric oxide (NOx) levels were measured using
      commercially available colorimetric kits, blood superoxide dismutase (SOD)
      activity was measured by the method of Marklund and Marklund, and plasma C
      peptide, oxidized LDL (ox-LDL), sRAGE, and VCAM-1 levels were measured using
      competitive ELISA kits. RESULTS: Plasma sRAGE levels were significantly lower (p
      < 0.05) while VCAM-1 levels were significantly higher (p < 0.05) in poorly
      controlled diabetic patients compared with healthy control. Blood GSH levels were
      significantly lower in diabetic patients compared with healthy control (p <
      0.05). Plasma C-peptide, NOx, ox-LDL levels, and SOD activity were not
      significantly different in diabetic patients compared with healthy control.
      Plasma levels of sRAGE were negatively associated with circulating VCAM-1 levels
      in diabetic patients. CONCLUSION: Poor glycemic control decreases plasma sRAGE
      and increases VCAM-1 levels while good glycemic control improves these
      abnormalities which provides benefit to diabetic patients.

PMID- 23964835
TI  - Reply: To PMID 22117934.

PMID- 23964836
TI  - High precision systems require high precision "blueprints": a new view regarding
      the formation of connections in the Mammalian visual system.
AB  - Abstract It is well established that early in development interconnections within
      the mammalian visual system are often more widespread and less precise than at
      maturity. The literature dealing with the formation of visual connections has
      largely ignored differences in developmental specificity among species differing
      in their phylogenetic status and/or the visual ecological niche that they occupy.
      Based on a review of the available evidence, we have formulated an hypothesis to
      account for the varying degrees of developmental specificity that characterize
      different visual systems. It is suggested that extremely precise systems required
      for high-acuity binocular vision exhibit fewer presumed developmental errors than
      do visual systems characterized by poorer acuity and relatively crude depth
      perception. The developmental implications of the hypothesis are considered, and
      specific experiments are proposed to further test its validity. 

PMID- 23964837
TI  - Arm trajectory modifications during reaching towards visual targets.
AB  - Abstract In this paper we study the question of how an aimed arm movement is
      modified in response to a sudden change in target location occurring during the
      reaction or movement time. Earlier monkey and human studies demonstrated that
      aimed arm movements can be elicited in quick succession, without appreciable
      delays in responding to the target displacement, beyond the normal reaction time.
      Nevertheless, it is not yet clear how this motor task is performed. A first guess
      is that when a new visual stimulus appears the old plan is aborted and a new one
      conceived. Upon analyzing human arm movements, however, we find that the
      observations can be well accounted for by a different movement modification
      scheme. It appears that a new plan is vectorially added to the original plan.
      Among the implications of this result is the possibility of parallel planning of
      elemental movements and further support for the idea that arm movements are
      internally represented in terms of hand motion through external space. 

PMID- 23964838
TI  - Deficits in selective attention following bilateral anterior cingulotomy.
AB  - Abstract Positron emission tomographic (PET) studies of normal humans undergoing
      specific cognitive activation paradigms have identified a region of the anterior
      cingulate cortex as a component of an anterior, midline attentional system
      involved in high-level processing selection. However, deficits in attention have
      not been demonstrated in patients following bilateral anterior cingulotomy, a
      procedure that results in lesions of adjacent anterior cingulate cortex. Task
      paradigms used in PET studies that recruit the anterior cingulate cortex were
      applied to normal, control subjects and to a patient before and after cingulotomy
      to provide highly sensitive and functionally targeted reaction time measures of
      attentional performance. In contrast to unchanged performance in several
      neuropsychological measures, this patient demonstrated specific deficits in
      attention during the subacute postoperative period, which resolved spontaneously
      several months after surgery. Such impairment is consistent with the evolving
      view of the anterior cingulate's involvement in high-level processing selection.
      These data show the feasibility of using information from PET activation studies
      of normals in the design of novel chronometric tasks useful for probing
      abnormalities in specific cognitive operations associated with discrete cortical
      regions. 

PMID- 23964839
TI  - Spatio-temporal cortical patterns evoked in monkeys by a discrimination task.
AB  - Abstract The primary experimental objective of this work was to demonstrate
      localization and temporal sequencing of the functional steps carried out by
      nonhuman primate subjects during performance of a sensory discrimination task,
      i.e., to identify the locale and sequence of activation of regions that
      participate in sensory discrimination, stimulus classification, and response
      preparation. Multivariate statistical procedures were applied to evoked
      transcortical recordings to identify the location and order of occurrence of
      signals that are effective in discriminating task conditions and parameters. (1)
      Sensory discrimination, (2) stimulus classification, and (3) response preparation
      occurred in the expected sequence. Information that enabled discrimination using
      these procedures was distributed widely across the cortex; however, the maximum
      information content was localized to striate and prestriate cortex, anterior
      inferior parietal cortex, and temporal and premotor cortex, respectively. This
      work provides a perspective on brain mechanisms responsible for cognition and
      demonstrates a set of powerful multivariate analytic tools for functional
      mapping, i.e., identifying the location and sequencing of cognitive functions. 

PMID- 23964840
TI  - Visual experience specifically regulates synaptic molecules in rat visual cortex.
AB  - Abstract To study environmental modulation of synaptic molecular structure, the
      major postsynaptic density protein (mPSDp) from rat visual cortex was monitored.
      This membrane component, a Ca(2+)/calmodulin-dependent protein kinase subunit,
      was measured during normal postnatal development and after visual deprivation.
      Total synaptic membrane (SM) protein was used as an index of synapses as a whole.
      During the first 2 postnatal months, total SM protein in the visual cortex
      increased 32-fold. In contrast, the mPSDp increased 455-fold, indicating that
      different molecular components of the cortical synapse develop differentially.
      Exposure to complete darkness during the first 2 postnatal weeks prevented normal
      development of total SM protein in visual cortex, values reaching only 66% of
      normal. Moreover, environmental lighting preferentially modulated the mPSDp,
      which attained only 34% of the normal value after dark rearing. Thus, visual
      deprivation selectively inhibited the normal development of specific synaptic
      components. Moreover, experience-dependent modulation was area specific. In
      contrast to the marked effect in visual cortex, light deprivation did not alter
      synapses in the nonvisual parietal and prefrontal cortices. Finally, the
      modulation of visual cortex mPSDp was stage specific, since visual experience did
      not alter the synaptic protein in adults. Our results suggest that early visual
      experience selectively and specifically modifies molecular synaptic components in
      the visual cortex. 

PMID- 23964841
TI  - Differential Sensitivity to Errors of Agreement and Word Order in Broca's
      Aphasia.
AB  - Abstract We investigated the effect of morphosyntactic violation type on accuracy
      and processing time in Broca's aphasics engaged in an on-line error detection
      task. Five agrammatic Broca's aphasic subjects and 15 age-matched control
      subjects performed grammaticality judgments on auditorily presented grammatical
      and ungrammatical sentences. Both judgment accuracy and decision time were
      measured, so that the data revealed not only whether aphasics detected
      violations, but when they noticed them. The ungrammatical sentences were created
      by changing quantifiers and auxiliary verbs in one of two ways: substituting one
      quantifier or auxiliary for another to create agreement errors, or moving the
      quantifier or auxiliary "downstream" from its proper site to create word order
      errors. Also, the position of the violation in the sentence (early versus late)
      as well as the distance relationships among sentence elements involved in the
      violation (local versus global) were manipulated. Results suggest that aphasic
      subjects retain some sensitivity to grammaticality, knowledge that they are able
      to use "online." Performance was also affected by type of violation. Aphasic
      subjects were less sensitive to agreement violations than they were to violations
      created by moving the same elements to an illegal position-and this tended to be
      reflected in decision times as well as accuracy. These results support two
      conclusions. First, although the performance of aphasic subjects was degraded
      relative to control subjects, the findings of overall grammaticality sensitivity
      and relatively rapid decision times suggest that the locus of grammatical
      impairment in these patients has more to do with the accessing of linguistic
      information than with loss of linguistic knowledge. Second, the difference
      between agreement and movement violations provides further evidence that
      morphological marking is relatively vulnerable in aphasia, compared with the
      principles that govern word and morpheme ordering. 

PMID- 23964842
TI  - A connectionist model may shed light on neural mechanisms for visually guided
      reaching.
AB  - Abstract Formal principles of vision-based planning and control of arm movements
      are used to gain insight into the neurobio-logical mechanisms that underlie this
      important class of sen-sorimotor behavior. The primary conceptual tool used in
      this work has been a neurally inspired connectionist system called MURPHY that
      learns to reach for visual targets among obstacles, crudely based on the style of
      architecture and representations in sensory and motor areas of cerebral cortex.
      This system has provided a concrete implementation that demonstrates how areas of
      cerebral cortex could in principle interact to direct both sensory-locked and
      internally planned reaching movements. We use MURPHY'S simple, artificial
      "cortex" as a point of departure in the development of two high-level cortical
      models for visual limb control, involving the supplementary motor area (SMA),
      areas 5 and 7 of the posterior parietal lobe, and several visually responsive
      areas including V2, PO, and areas TPO and STP in the upper bank of the superior
      temporal sulcus. 

PMID- 23964843
TI  - Short-latency single unit processing in olfactory cortex.
AB  - Abstract Single-unit recording of layer II-III cells in olfactory (piriform)
      cortex was performed on awake, unrestrained rats actively engaged in learning
      novel odors in an olfactory discrimination task. Five of the 67 cells tested had
      very brief monophasic action potentials and high spontaneous firing rates (30-80
      Hz); it is suggested that these units were interneurons. The remainder of the
      neurons had broader spikes and did not discharge for prolonged periods. Thirty
      nine percent of the broad spike cells responded to at least one and usually more
      of the odors presented to the rats during either of the first two trials on which
      that odor was present, but, in most cases, these responses occurred only very
      infrequently over the course of subsequent trials. Six percent of the broad-spike
      group, how ever, continued firing robustly to a single odor but not to others.
      From these results it appears that most cells in piriform cortex do not respond
      to most odors, i.e., coding is exceedingly sparse. A subgroup of the predominant
      broad-spike cell type does react to several odors but this response drops out
      with repeated exposure, perhaps because of training. However, a few members of
      this class (a small fraction of the total cell population) do go on responding to
      a particular odor, thus exhibiting a form of odor specificity. The results are
      discussed with regard to predictions from recently developed models of the
      olfactory cortex. 

PMID- 23964844
TI  - New ideas on the structure of the nervous system in man and vertebrates.

PMID- 23964845
TI  - Unified theories of cognition.

PMID- 23964846
TI  - Using the quartz crystal microbalance with dissipation monitoring to evaluate the
      size of nanoparticles deposited on surfaces.
AB  - A quartz crystal microbalance with dissipation (QCM-D) monitoring can be an
      alternative tool to characterize nanoparticle size by virtue of its acoustic
      principle to sense adsorbed mass. In this study, sizes obtained by QCM-D for
      polymer-coated metallic nanoparticles and polydisperse polystyrene latex particle
      suspensions were compared with those obtained by transmission electron microscopy
      (TEM) and dynamic light scattering (DLS). We describe the obtained "QCM-D mass",
      which is weighted over surface area, by a general particle height distribution
      equation that can be used to determine the average particle diameter of a
      distribution of particles deposited on the QCM-D surface. Because the particle
      height distribution equation can be used for any particle geometry and surface
      packing geometry, it is described how the QCM-D can also be used to study the
      orientation of deposited nonspherical particles. Herein, the mean nanoparticle
      sizes obtained by QCM-D were generally in closer agreement with the primary
      particle size determined by TEM than with the sizes obtained by DLS, suggesting
      that primarily smaller particles within the particle population deposited on the
      sensor surface. Overall, the results from this study demonstrate that QCM-D could
      serve as an alternative and/or complementary means to characterize the size of
      nanoparticles deposited on a surface from suspensions of varying complexity. 

PMID- 23964847
TI  - Characteristics of women who have repeat abortions in the Netherlands.
AB  - OBJECTIVES: To explore the demographic characteristics of women having multiple
      abortions, in order to identify abortion clients who might be at increased risk
      of repeat abortion. METHODS: On the basis of the registration data of most Dutch
      abortion clinics, responsible for 64% of all such procedures, women who procured
      a first abortion were compared to those who had one or more previously. Results
      of bivariate analyses and a multivariate binary logistic regression analysis are
      presented. RESULTS: Of all abortions, 36% were repeat abortions. Women aged over
      20 were more likely to have repeat abortions, as were migrants, particularly
      those with a Caribbean background (from Surinam or the Netherlands Antilles) and
      women who had children. Effect sizes of other factors were very small.
      Surprisingly, women who had repeat abortions more often used contraception in the
      preceding six months than women who had a first abortion, but also this effect
      size was small as well. A multivariate logistic regression analysis led to
      similar results. CONCLUSIONS: Abortion clients with a Caribbean background should
      be targeted for the prevention of more unwanted pregnancies. Not only should the
      use of reliable contraception be promoted, but also compliance and continuation.

PMID- 23964848
TI  - Quantitative analysis of fall risk using TUG test.
AB  - We examined falling risk among elderly using a wearable inertial sensor, which
      combines accelerometer and gyrosensors devices, applied during the Timed Up and
      Go (TUG) test. Subjects were categorised into two groups as low fall risk and
      high fall risk with 13.5 s duration taken to complete the TUG test as the
      threshold between them. One sensor was attached at the subject's waist dorsally,
      while acceleration and gyrosensor signals in three directions were extracted
      during the test. The analysis was carried out in phases: sit-bend, bend-stand,
      walking, turning, stand-bend and bend-sit. Comparisons between the two groups
      showed that time parameters along with root mean square (RMS) value, amplitude
      and other parameters could reveal the activities in each phase. Classification
      using RMS value of angular velocity parameters for sit-stand phase, RMS value of
      acceleration for walking phase and amplitude of angular velocity signal for
      turning phase along with time parameters suggests that this is an improved method
      in evaluating fall risk, which promises benefits in terms of improvement of
      elderly quality of life.

PMID- 23964849
TI  - Odorant receptors of a primitive hymenopteran pest, the wheat stem sawfly.
AB  - The wheat stem sawfly, Cephus cinctus, is an herbivorous hymenopteran that feeds
      exclusively on members of the Graminae family. Synanthropically, it has become
      one of the most important insect pests of wheat grown in the northern Great
      Plains region of the USA and Canada. Insecticides are generally ineffective
      because of the wheat stem sawfly's extended adult flight period and its
      inaccessible larval stage, during which it feeds within the wheat stems, making
      it virtually intractable to most pest management strategies. While research
      towards integrated pest management strategies based on insect olfaction has
      proved promising, nothing is known about the molecular basis of olfaction in this
      important pest species. In this study we identified 28 unique odorant receptor
      (Or) transcripts from an antennal transcriptome. A phylogenetic analysis with the
      predicted Ors from the honey bee and jewel wasp genomes revealed at least four
      clades conserved amongst all three Hymenoptera species. Antennal expression
      levels were analysed using quantitative real-time PCR, and one male-biased and
      five female-biased Ors were identified. This study provides the basis for future
      functional analyses to identify behaviourally active odours that can be used to
      help develop olfactory-mediated pest management tools. 

PMID- 23964851
TI  - 7-Hydroxyquinoline-8-carbaldehydes. 2. Prototropic equilibria.
AB  - Prototropic equilibria were studied for a series of 7-hydroxyquinoline-8
      carbaldehydes (7-HQCs) by (1)H NMR spectroscopy, photostationary and time
      resolved UV-vis spectroscopic methods, and quantum chemical computations. These
      molecules represent trifunctional proton-donating/accepting systems that in
      aqueous solutions may assume four main neutral and ionic structures: 7-quinolinol
      (OH), 7(1H)-quinolinone (NH), deprotonated anion (A), and protonated cation (C).
      Electronic absorption and fluorescence of 7-HQCs are rationalized in terms of the
      ground and excited-state long-range tautomerization (part 1) as well as
      protonation and deprotonation processes. The photophysical properties of neutral
      and ionic forms of 7-HQCs are compared with those of 7-hydroxyquinolines (7-HQs),
      synthetic precursors of the former. The experimental results are corroborated by
      ab initio computations. 

PMID- 23964850
TI  - Suppression of ovine lymphocyte activation by Teladorsagia circumcincta larval
      excretory-secretory products.
AB  - Teladorsagia circumcincta is an important pathogenic nematode of sheep. It has
      been demonstrated previously that stimulation of murine T lymphocytes with
      excretory-secretory (ES) products derived from fourth stage larvae of T.
      circumcincta (Tci-L4-ES) results in de novo expression of Foxp3, a transcription
      factor intimately involved in regulatory T cell function. In the current study,
      Foxp3+ T cell responses in the abomasum and the effects of Tci-L4-ES on ovine
      peripheral blood mononuclear cells (PBMC) following T. circumcincta infection
      were investigated. T. circumcincta infection resulted in a significant increase
      in numbers of abomasal Foxp3+ T cells, but not an increase in the proportion of T
      cells expressing Foxp3. Unlike in mice, Tci-L4-ES was incapable of inducing T
      cell Foxp3 expression but instead suppressed mitogen-induced and antigen-specific
      activation and proliferation of ovine PBMC in vitro. This effect was heat labile,
      suggesting that it is mediated by protein(s). Suppression was associated with up
      regulation of interleukin-10 (IL-10) mRNA, and specific monoclonal antibody
      neutralisation of IL-10 resulted in a 50% reduction in suppression, indicating
      involvement of the IL-10 signaling pathway. Suppression was significantly reduced
      in PBMC isolated from T. circumcincta infected vs. helminth-naive lambs, and this
      reduction in suppression was associated with an increase in Tci-L4-ES antigen
      specific T cells within the PBMC. In conclusion, we have identified a mechanism
      by which T. circumcincta may modulate the host adaptive immune response,
      potentially assisting survival of the parasite within the host. However, the
      impact of Tci-L4-ES-mediated lymphocyte suppression during T. circumcincta
      infection remains to be determined.

PMID- 23964852
TI  - The toxicity of energy drinks: myth or reality?

PMID- 23964854
TI  - A 13-year review of lisinopril ingestions in children less than 6 years of age.
AB  - BACKGROUND: Lisinopril is an angiotensin converting enzyme inhibitor used for
      treatment of hypertension, congestive heart failure, and acute myocardial
      infarction. Reports of clinical experience with pediatric ingestions are minimal.
      METHOD: A 13-year retrospective study of lisinopril ingestions in children
      reported to the California Poison Control System was analyzed and case notes were
      reviewed. Institutional Review Board approval was obtained and cases were
      blinded. Inclusion criteria were lisinopril as a single ingestant, age less than
      6 years, treatment in a health care facility, case followed to a known outcome.
      RESULTS: Inclusion criteria were met in 296 cases. Demographics include 51% of
      male patients and the mean age was 1.97 years (range: 9 months-5 years). Of the
      296 patients, 8 patients (2.7%) developed hypotension (ranges: 55-74 mm Hg
      systolic and 22-48 mm Hg diastolic). The lowest blood pressure of 55/22 mm Hg was
      recorded in a 22-month old male who ingested an estimated 120-mg lisinopril (13.3
      mg/kg). The lowest dose of lisinopril causing hypotension was with an estimated
      dose of approximately 50 mg or 3.9 mg/kg in a 2-year old. Two hundred and eighty
      two patients (95.3%) were treated and released from the emergency department and
      14 patients (4.7%) were admitted. The dose ingested was reported in 189 cases and
      an exact-dose of lisinopril was reported in 61 patients (20.6%); mean amount
      ingested was 3.0 mg/kg, median amount ingested was 2.1 mg/kg (range: 0.1-10.9
      mg/kg, N = 38); and mean total dose was 33.4 mg, median total dose was 20 mg
      (range: 2.5-160 mg, N = 61). None of the patients with exact-dose lisinopril
      ingestions developed hypotension, received intravenous fluids, or were admitted.
      CONCLUSION: The lowest estimated dose of lisinopril to cause hypotension was 50
      mg or 3.9 mg/kg. Although continued evaluation of pediatric lisinopril ingestions
      is essential to determine more specific thresholds of toxicity, the lack of
      effect on blood pressure in children with exact-dose ingestions indicate that
      pediatric lisinopril ingestions (for ages > 9 months) <= 4 mg/kg up to 40 mg
      total may be safely managed at home.

PMID- 23964853
TI  - Predicting the requirement for N-acetylcysteine in paracetamol poisoning from
      reported dose.
AB  - CONTEXT: There is contention over whether reported dose correlates with toxicity
      in paracetamol poisoning and risk assessment is currently based on serum
      paracetamol concentration compared to a nomogram, irrespective of reported dose.
      Objective. To determine if reported dose predicts the need for N-acetylcysteine
      (NAC). METHODS: Data were taken from paracetamol overdoses presenting to a
      tertiary toxicology service. Age, sex, reported dose, ingestion time, timed
      paracetamol concentrations between 4 and 16 h, hepatotoxicity (peak alanine
      transaminase > 1000 U/L) and treatment (single dose-activated charcoal [SDAC] and
      NAC) were analysed. Data were analysed within a repeated measures logistic
      regression framework using NONMEM (ver 7.2). The primary outcome was
      administration of NAC, which was determined based on a serum paracetamol
      concentration greater than the nomogram line. RESULT: There were 1571 admissions
      in 1303 patients, with a median age of 27 years (12-96 years) and 1140 (73%) were
      females. The median dose was 10 g (1-100 g). The paracetamol concentration was
      above the nomogram line in 337 of 1571 (22%) patients. Patients presenting later
      (first paracetamol concentration between 7 and 16 h post-overdose) compared to
      those presenting earlier (4-7 h post-overdose) were more likely to have
      hepatotoxicity (5.5% vs. 0.4%; p < 0.0001), have a toxic paracetamol
      concentration (34% vs. 18%; p < 0.0001) and receive NAC (48% vs. 23%; p <
      0.0001). SDAC reduced the probability of the paracetamol concentration being
      above the nomogram. Based on SDAC not being administered there was a 5%
      probability of requiring NAC at a dose of 6-9 g, a 10% chance of requiring NAC at
      a dose of 13-16 g, a 50% chance of requiring NAC at a dose of 30-34 g and a 90%
      chance for needing NAC at 48-50 g. CONCLUSION: Reported dose was a good predictor
      of a toxic paracetamol concentration and SDAC reduced the probability of the
      concentration being above the nomogram. These predictions may assist in
      determining which patients could be started on NAC immediately.

PMID- 23964855
TI  - Demographics and outcome of unintentional insulin overdoses managed by three
      poison centers.
AB  - Insulin dosing errors are one of the most dangerous medication issues due to the
      risk of profound hypoglycemia. The incidence of insulin dosing errors is
      increasing and there is no standard of care for management location. OBJECTIVE:
      To determine the types of insulin, follow-up time, number of phone calls,
      incidence of hypoglycemia, and case outcomes for unintentional insulin overdoses
      managed by Poison Centers (PCs). METHODS: Observational case series: records of
      patients with unintentional injected insulin errors from three PCs over a 22
      month period were manually reviewed for insulin type, management site, time of
      exposure, insulin dose, number of calls, presence of hypoglycemia, and case
      outcome. RESULTS: There were 642 cases: 97.5% occurred in the home and the
      majority of patients (77.3%) were managed on site with only 17.4% resulting in
      Emergency Department treatment. Clinical or numerical (blood sugar < 60 mg/dL)
      hypoglycemia occurred 15.9% (n = 102) of the time in all cases, with 6.9% (n =
      41) of cases having numerical hypoglycemia. The median insulin dose when known
      was 40 Units, with short-acting insulin making up the majority of cases (64.3%)
      with 13.8% of cases having a dose error of 80 or more units. The average duration
      of follow-up was 6.9 h. The frequency of hypoglycemia (clinical or numerical) did
      not differ between short and non-short duration insulin cases (15.7% vs. 16.9%, n
      = 65 vs. 37, p = 0.91), did not differ with cases receiving more than 50 Units of
      insulin (14.9% vs. 16.7%, n = 29 vs. 73, p = 0.64), and did not differ between
      those managed on site and other management locations (14.4% vs. 21.4%, n = 71 vs.
      31, p = 0.053). Outcomes were benign in the majority of cases and there were no
      cases with Major (severe) outcomes or Death. CONCLUSION: Insulin dosing accidents
      can be routinely managed at home by PCs and have a low rate of hypoglycemia and
      adverse outcomes. This suggests that these cases can often be managed at home
      without referral with a potential benefit in no direct cost to the patient,
      convenience, and immediacy.

PMID- 23964856
TI  - Study of the interaction among Notch pathway receptors, correlation with
      stemness, as well as their interaction with CD44, dipeptidyl peptidase-IV,
      hepatocyte growth factor receptor and the SETMAR transferase, in colon cancer
      stem cells.
AB  - CONTEXT: The Notch signaling pathway is one of the most important pathways during
      normal development and implicated in self-renewal of adult stem cells and
      differentiation of progenitor cells. Abnormal expression of Notch receptors has
      been associated with many epithelial metaplastic and neoplastic lesions.
      OBJECTIVE-MATERIALS AND METHODS: In this particular study, it was determined the
      relative gene expression of Notch receptors after knockdown experiments in colon
      cancer stem cells (CSCs) and the gene expression changes in stemness
      transcription factors (Oct4, Sox2, Nanog), as well in dipeptidylpeptidase-4, CD44
      antigen, Met proto-oncogene and in Metnase transposase. RESULTS: In control CSCs
      Notch-2 had the higher expression, followed by Notch-1, Notch-3. Notch-4
      demonstrated the lower gene expression among the receptors. The suppression of
      Notch-1 led to increased expression of Oct4 and Sox2, but in decreased gene
      expression of cMET, Setmar and CD44. The CD26 expression remained unchanged. The
      knockdown of Notch-2 led to decreased expression of all transcription factors.
      Notch-3 down regulation caused increased Oct4 gene expression, but decreased
      levels for the rest of the genes. Finally, the suppression of Notch-4 had the
      same effect as in receptor Notch-3. DISCUSSION AND CONCLUSION: The above
      experimental data suggest the possible interaction between the four different
      receptors of Notch signaling pathway. The expression of CD26, cMET and N
      methyltransferase Setmar was also changed. Finally, the stemness phenotype was
      changed in a different way each time, according to the receptor that was down
      regulated. All Notch receptors and particularly Notch-2 seem to play an important
      role in cancer stem cells.

PMID- 23964857
TI  - What interventions do rural doctors think will increase recruitment in rural
      areas: a survey of 2778 health workers in Beijing.
AB  - BACKGROUND: A shortage of health professionals in rural areas is a major problem
      facing China, as more than 60% of the population lives in such areas. Strategies
      have been developed by the government to improve the recruitment of rural
      doctors. However, the inequitable distribution of doctors working in China has
      not improved significantly. The objective of this study was to explore the
      reasons for the poor recruitment and to propose possible strategies to improve
      the situation. METHODS: Between September 2009 and November 2009 data were
      collected from 2778 rural doctors in Beijing, China. A quantitative survey was
      used to explore health workers' perceptions as to what factors would have the
      greatest impact on recruitment and whether access to training had been effective
      in increasing their confidence, enhancing their interest in practicing medicine
      and increasing their commitment to recruitment. RESULTS: Rural doctors were
      generally older than average in China. Of the 2778 participants, only 7.23% had
      obtained a license as a qualified doctor. For 53% of the rural doctors, the job
      was part-time work. The survey showed that rural doctors considered the training
      strategy to be inadequate. In general, the initiatives identified by rural
      doctors as being of most value in the recruitment of doctors were those targeting
      retirement pension and income. CONCLUSIONS: From the perspective of rural
      doctors, specific initiatives that promised a secure retirement pension and an
      increased income were considered most likely to assist in the recruitment of
      rural doctors in Beijing.

PMID- 23964858
TI  - Quantum chemical study on formation of PCDT/TA from 2-chlorothiophenol precursor.
AB  - This contribution investigates the thermochemical and kinetic parameters
      pertinent to the homogeneous gas-phase formation of two groups of pollutants,
      polychlorinated dibenzothiophenes (PCDT) and polychlorinated thianthrenes (PCTA)
      from their 2-chlorothiophenol (2-CTP) precursor. We compare the enthalpic
      profiles of the formation mechanism of PCDT/TA with the corresponding reactions
      involved in the gas-phase synthesis of PCDD/F (polychlorinated dibenzo-p-dioxins
      and polychlorinated dibenzofurans, also known as dioxins). Overall, the presence
      of sulfur atoms greatly reduces the activation enthalpies of the rate determining
      steps in reference to the oxygenated system of PCDD/F. The rate constants of all
      elementary reactions are calculated using the transition state theory (TST) over
      a wide temperature range of 300-1200 K. We performed kinetic calculations for the
      formation of chlorinated dibenzothiophenes and chlorinated thianthrenes that
      could be applied to predict yields of these pollutants from 2-CTP up to ~1200 K,
      that is, prior to the emergence of dechlorination and oxidation reactions. The
      results presented herein provide a greatly improved understanding of the gas
      phase formation of the sulfur analogs of the notorious dioxins compounds. 

PMID- 23964859
TI  - Identification of a novel series of orexin receptor antagonists with a distinct
      effect on sleep architecture for the treatment of insomnia.
AB  - Dual orexin receptor (OXR) antagonists (DORAs) such as almorexant, 1 (SB-649868),
      or suvorexant have shown promise for the treatment of insomnias and sleep
      disorders in several recent clinical trials in volunteers and primary insomnia
      patients. The relative contribution of antagonism of OX1R and OX2R for sleep
      induction is still a matter of debate. We therefore initiated a drug discovery
      project with the aim of creating both OX2R selective antagonists and DORAs. Here
      we report that the OX2R selective antagonist 26 induced sleep in mice primarily
      by increasing NREM sleep, whereas the DORA suvorexant induced sleep largely by
      increasing REM sleep. Thus, OX2R selective antagonists may also be beneficial for
      the treatment of insomnia. 

PMID- 23964860
TI  - Characterization of three deoxynivalenol sulfonates formed by reaction of
      deoxynivalenol with sulfur reagents.
AB  - Reduction of the Fusarium mycotoxin deoxynivalenol (DON) in animal feed by
      treatment with sodium bisulfite and sodium metabisulfite has been successfully
      demonstrated in several studies. All of them reported formation of one DON
      sulfonate of strongly reduced toxicity compared to DON. The starting point of the
      present work was investigation of different sulfur reagents for reduction of DON.
      In the course of these experiments, three different DON sulfonates termed DON
      sulfonate 1 (1), DON sulfonate 2 (2), and DON sulfonate 3 (3) were identified and
      structurally elucidated by UHPLC-HRMS/MS as well as NMR spectroscopy. Compound 1
      is characterized by loss of the epoxide group, and 2 by formation of a hemiketal.
      Compound 3 is an equilibrating mixture of two isomers, a ketone and a hemiketal.
      The MS/MS pattern can be used to differentiate the three DON sulfonates, despite
      their same mass and molecular formula. Investigation of parameters influencing
      formation and stability of DON sulfonates revealed that rapid formation of 1 and
      2 occurs at alkaline pH, whereas at acidic pH, slow formation of 3 takes place,
      irrespective of the sulfur reagent used. Whereas 1 and 2 are stable across a
      broad pH range, 3 decomposes to DON, 1, and 2 at alkaline pH. In addition, both 2
      and 3 are unstable in solid form. The formation, characterization, and stability
      of three novel DON sulfonates with respect to results from previous studies are
      discussed, providing insights of relevance for detoxification of DON-containing
      animal feed. 

PMID- 23964861
TI  - Sound advice for heart murmurs.

PMID- 23964862
TI  - Rabbit dental disease and calcium metabolism--the science behind divided
      opinions.
AB  - Dental disease is considered as one of the, if not, the most common disorders
      seen in pet rabbits. This article provides a review of the scientific literature
      and an overview of the peculiarities of calcium homeostasis in the rabbit in an
      attempt to draw together current thinking on the cause of dental disease. A
      complete understanding of the aetiology and pathophysiology of rabbit dental
      disease is necessary for the veterinary practitioner to establish a proper
      therapeutic plan, prognosis and ultimately prevention of this common cause of
      morbidity and mortality in pet rabbits. 

PMID- 23964863
TI  - Sperm maturation in dogs: sperm profile and enzymatic antioxidant status in
      ejaculated and epididymal spermatozoa.
AB  - Spermatozoa become more susceptible to the attack of reactive oxygen species
      during maturation. To avoid oxidative damage, the epididymis must provide the
      necessary antioxidant protection. The aim of this study was to compare the canine
      sperm profile and the enzymatic antioxidant status of the ejaculated fractions
      and samples collected from the different segments of the epididymis (caput,
      corpus and cauda). Five adult dogs were used, and after 1-3 weeks, subsequently
      to bilateral orchiectomy and epididymal storage, sperm samples were collected
      from the different segments of the epididymis. Samples were evaluated for
      conventional microscopy and computer-assisted motility analysis: sperm plasma
      membrane permeability and the activity of the antioxidant enzymes catalase,
      glutathione peroxidase (GPx) and superoxide dismutase (SOD). Samples collected
      from the caput and corpus showed lower values for most of the motility variables
      evaluated, indicating different levels of immaturity. Catalase activity was
      observed only in ejaculated samples. Conversely, GPx activity was higher in the
      cauda epididymidis. Correlations were found between SOD and GPx and SOD and sperm
      motility in the epididymal cauda and corpus, highlighting the importance of the
      enzymes for the protection of spermatozoa during the transit along the
      epididymis.

PMID- 23964864
TI  - Population-based incidence and comparative demographics of community-associated
      and healthcare-associated Escherichia coli bloodstream infection in Auckland, New
      Zealand, 2005-2011.
AB  - BACKGROUND: Escherichia coli is a major human pathogen, both in community and
      healthcare settings. To date however, relatively few studies have defined the
      population burden of E. coli bloodstream infections. Such information is
      important in informing strategies around treatment and prevention of these
      serious infections. Against this background, we performed a retrospective,
      population-based observational study of all cases of E. coli bacteremia in
      patients presenting to our hospital between January 2005 and December 2011.
      METHODS: Auckland District Health Board is a tertiary-level, university
      affiliated institution serving a population of approximately 500,000, within a
      larger metropolitan population of 1.4 million. We identified all patients with an
      episode of bloodstream infection due to E. coli over the study period. A unique
      episode was defined as the first positive E. coli blood culture taken from the
      same patient within a thirty-day period. Standard definitions were used to
      classify episodes into community- or healthcare-associated E. coli bacteremia.
      Demographic information was obtained for all patients, including: age; gender;
      ethnicity; length of stay (days); requirement for intensive care admission and
      all-cause, in-patient mortality. RESULTS: A total of 1507 patients had a unique
      episode of E. coli bacteremia over the study period. The overall average annual
      incidence of E. coli bacteremia was 52 per 100,000 population, and was highest in
      the under one year and over 65-year age groups. When stratified by ethnicity,
      rates were highest in Pacific Peoples and Maori (83 and 62 per 100,000 population
      respectively). The incidence of community-onset E. coli bacteremia increased
      significantly over the study period. The overall in-hospital mortality rate was
      9% (135/1507), and was significantly higher in patients who had a hospital-onset
      E. coli bacteremia. CONCLUSIONS: Our work provides valuable baseline data on the
      incidence of E. coli bacteremia in our locale. The incidence was higher that that
      described from other developed countries, with significant demographic variation,
      most notably in ethnic-specific incidence rates. Future work should assess the
      possible reasons for this disparity.

PMID- 23964865
TI  - The charge transfer problem in density functional theory calculations of
      aqueously solvated molecules.
AB  - Recent advances in algorithms and computational hardware have enabled the
      calculation of excited states with time-dependent density functional theory
      (TDDFT) for large systems of O(1000) atoms. Unfortunately, the aqueous charge
      transfer problem in TDDFT (whereby many spuriously low-lying charge transfer
      excited states are predicted) seems to become more severe as the system size is
      increased. In this work, we concentrate on the common case where a chromophore is
      embedded in aqueous solvent. We examine the role of exchange-correlation
      functionals, basis set effects, ground state geometries, and the treatment of the
      external environment in order to assess the root cause of this problem. We
      conclude that the problem rests largely on water molecules at the boundary of a
      finite cluster model, i.e., "edge waters." We also demonstrate how the TDDFT
      problem can be related directly to ground state problems. These findings demand
      caution in the commonly employed strategy that rests on "snapshot" cutout
      geometries taken from ground state dynamics with molecular mechanics. We also
      find that the problem is largely ameliorated when the range-separated hybrid
      functional LC-omegaPBEh is used. 

PMID- 23964867
TI  - Psychometric properties of the Hospital Survey on Patient Safety Culture, HSOPSC,
      applied on a large Swedish health care sample.
AB  - BACKGROUND: A Swedish version of the USA Agency for Healthcare Research and
      Quality "Hospital Survey on Patient Safety Culture" (S-HSOPSC) was developed to
      be used in both hospitals and primary care. Two new dimensions with two and four
      questions each were added as well as one outcome measure. This paper describes
      this Swedish version and an assessment of its psychometric properties which were
      tested on a large sample of responses from personnel in both hospital and primary
      care. METHODS: The questionnaire was mainly administered in web form and 84215
      forms were returned (response rate 60%) between 2009 and 2011. Eleven per cent of
      the responses came from primary care workers and 46% from hospital care workers.
      The psychometric properties were analyzed using both the total sample and the
      hospital and primary care subsamples by assessment of construct validity and
      internal consistency. Construct validity was assessed by confirmatory (CFA) and
      exploratory factor (EFA) analyses and internal consistency was established by
      Cronbachs's alpha. RESULTS: CFA of the total, hospital and primary care samples
      generally showed a good fit while the EFA pointed towards a 9-factor model in all
      samples instead of the 14-dimension S-HSOPSC instrument. Internal consistency was
      acceptable with Cronbach's alpha values above 0.7 in a major part of the
      dimensions. CONCLUSIONS: The S-HSOPSC, consisting of 14 dimensions, 48 items and
      3 single-item outcome measures, is used both in hospitals and in primary care
      settings in Sweden for different purposes. This version of the original American
      instrument has acceptable construct validity and internal consistency when tested
      on large datasets of first-time responders from both hospitals and primary care
      centres. One common instrument for measurements of patient safety culture in both
      hospitals and primary care settings is an advantage since it enables comparisons
      between sectors and assessments of national patient safety improvement programs.
      Future research into this version of the instrument includes comparing results
      from patient safety culture measurements with other outcomes in relation to
      safety improvement strategies.

PMID- 23964868
TI  - [Screening ROP in the University Hospital Ostrava].
AB  - OBJECTIVE: To analyze the group of premature infants who were examined by an
      ophthalmologist in screening for ROP (retinopathy of prematurity) at the
      University Hospital in Ostrava. METHODS: A retrospective observational case
      series. We reviewed and analyzed clinical records of all the premature infants
      born before the 32nd gestational week examined by ophthalmologist in ROP
      screening at the University Hospital in Ostrava in the period from 1. 9. 2011 to
      31. 8. 2012. Childrens gestational age at birth, birth weight, postconceptional
      age (PCA) of the child at the time of the first ocular inspection, at the time of
      diagnosis ROP and at the time of any intervention, possible risk factors of ROP
      (Apgar score in the 1st minute, duration of oxygen therapy, FiO2 (%) (percentage
      fraction of oxygen in the inspired gas mixture), duration of mechanical
      ventilation, transfusion of erythrocytes (resuspended leukodepleted), presence of
      sepsis / infection in the perinatal period and duration of phototherapy) were
      evaluated. Eye examination was performed in local anesthesia with the use of an
      eyelid retractor, in artificial mydriasis, using an indirect ophthalmoscope and
      digital imaging system RetCam 3. RESULTS: 138 premature infants with an average
      gestational age at birth of 29.8 weeks, average birth weight 1385 g, were
      included in this study. Thirty-four children (24.6 %) were diagnosed with ROP, in
      all cases 1st stage at the time of diagnosis. An ophthalmologist indicated and
      subsequently implemented intervention (cryotherapy / laser treatment) in the case
      of five children (14.7 %) with ROP under general anesthesia. Average duration of
      oxygen therapy at infants with ROP was 371 hours, in the group without ROP 84
      hours. The difference between the average values was statistically significant [t
      (37) = -3.69, P <= 0.0007]. Average time of mechanical ventilation in the case of
      children with ROP were 229 hours, in the group without ROP 41 hours [t (35) = 
      2.99, P <0.005]. In the case of children with ROP, we noticed on average 3
      transfusions of erythrocytes, in the group without ROP 1 transfusion [t (40) = 
      3.94, P <= 0.0003]. The average value of the Apgar score in the 1st minute of
      children with ROP group was 6.3 and children without ROP 7.8. The difference
      between the average values of Apgar score in the 1st minute was between both
      groups statistically significant [t (136) = 4.06, P <= 0.00008]. Sepsis /
      infection in the perinatal period occurred in 30 (88.2 %) children with ROP, in
      comparison with 46 (44.2 %) children with sepsis / infection without ROP. Average
      duration of phototherapy in infants with ROP was 42.4 hours, in the group without
      ROP 53.6 hours [t(136) = 1,21, P<= 0,2]. CONCLUSION: This study demonstrated
      statistically significant correlation of Apgar score in the 1st minute, duration
      of oxygen therapy, duration of mechanical ventilation, transfusion of
      erythrocytes and presence of sepsis / infection on the onset and progression of
      ROP at premature infants in our group. No effect of FiO2 (%) and duration of
      phototherapy on the onset and progression of ROP was demonstrated.

PMID- 23964869
TI  - [New possibilities screening of refractive errors among children].
AB  - PURPOSE: To establish early detection of refractive errors among children in
      Slovakia. Different screening methods have been evaluated and compared in this
      work. MATERIALS AND METHODS: we have been working on a prospective study. Pre
      school children in kindergardens in Central Slovakia were checked up between
      years 2009-2011. Effectiveness of various screening methods was compared within 2
      groups, using test-type and Plusoptix Vision Screener. Parentes of children
      positive to refractive errors were recommended to consult a paediatrician
      ophthalmologist. RESULTS: 3982 children were examined. As a result, 13-14.1% of
      children who have not been examinated by the specialist, were positive. 53.3% of
      them went to see the doctor afterwards. CONCLUSION: establishment of early
      refractive errors screening is an important method how to prevent strabismus and
      amblyopia. It is very important to improve parentes knowledge about the risk of
      refractive errors and also to improve screening methods with collaboration with
      kindergarten teachers.

PMID- 23964870
TI  - [The importance of angle kappa for centration of multifocal intraocular lenses].
AB  - PURPOSE: To evaluate patient satisfaction with multifocal intraocular lens (MIOL)
      implants (AcrySof Restor) in relation to the size of angle kappa and precise
      centration of the MIOL. METHODS: Fifty-two eyes of 26 patients were included in
      this study. All patients underwent bilateral phacoemulsification and multifocal
      intraocular lens implantation (AcrySof Restor) from January 2008 to April 2010.
      Preoperative and postoperative examinations included slit lamp biomicroscopy,
      near and distance uncorrected visual acuity (UCVA) and best-corrected visual
      acuity (BCVA), contrast sensitivity and measurement of angle kappa. Precise
      centration of the IOL with respect to the centre of the pupil was evaluated
      postoperatively. Subjective photic phenomena were evaluated separately for each
      eye and the patients were asked to compare the perception between the right and
      left eye. RESULTS: Angle kappa was positive in all cases, ranging from +1 degrees
      to +7 degrees . The mean angle kappa was 2.78 degrees  and 2.10 degrees  in the
      right and left eye, respectively. The IOL was centred exactly to the centre of
      the pupil in 40 eyes. In twelve eyes there was a slight decentration of the IOL
      (3 nasal, 4 temporal, 2 superotemporal, 2 superior, 1 inferior). Different
      subjective perception of photic phenomena between the two eyes was recorded only
      in five patients. All these patients were among those with a decentred IOL.
      Temporal and superotemporal decentration of the IOL caused pronounced photic
      phenomena in five cases - in four cases there was a greater angle kappa of +3
      degrees  to +4 degrees . In one case of temporal decentration and a small angle
      kappa (+1 degrees ), the patient failed to observe a difference between both
      eyes. In the cases of inferior, superior and nasal decentration of the IOL, no
      difference between both eyes was seen. CONCLUSION: According to our results,
      temporal decentration of the IOL is associated with the greatest risk in
      multifocal IOL implantation, particularly in cases with a higher angle kappa. An
      evaluation of angle kappa should be a part of preoperative examination before
      MIOL implantation. Patients with a high angle kappa should be excluded because of
      a higher risk of postoperative photic phenomena. Key words: angle kappa,
      multifocal intraocular lens, photic phenomena.

PMID- 23964871
TI  - [Myopia or hyperopia?].
AB  - INTRODUCTION: The study describes cases of patients screened for worse vision and
      headaches. We are trying to point out we can measure minus diopters even at
      latent hypemetropes. These patients come to a doctor for a variety of problems
      that may be caused by inadequate correction of ametropia. It is necessary to know
      about this possibility, and rather perform cycloplegia in sporadic cases.
      METHODS: Patients were measured at autorefractometer without mydriasis, and then
      after using UNITROPIC 1% or CYCLOGYL 1%. Both of these substances induce
      cycloplegia. Visual acuity with the best correction was tested with and without
      cycloplegia. RESULTS: After cycloplegia, a significant change in both objective
      and subjective refraction was detected in most of the selected patients. This
      change was within the meaning of a shift to hyperopia. Subsequent adjustment
      correction led to resolving of problems. CONCLUSION: The work should highlight
      the necessity of an individual approach of prescription of the best correction.
      Not always an autorefractometer gives correct information, the real-needed
      correction is completely different in some cases.

PMID- 23964872
TI  - [HDR 192Ir brachytherapy in treatment of basal cell carcinoma of the lower eyelid
      and inner angle - our experience].
AB  - PURPOSE: First experience and evaluation of relapses in group of patients after
      surgery with applied adjuvant HDR brachytherapy for recurrent tumor after
      incomplete excision of basal cell carcinoma of the lower eyelid and inner angle.
      METHODS: Patients with recurrent basal cell carcinoma of the lower eyelid in year
      2010. In 3 male patients with recurrent finding of basal cell after surgery we
      applied adjuvant HDR 192Ir brachytherapy. The isodose curve chosen to prescribe
      the dose was 5 mm away from the skin surface. RESULTS: In the year 2010 we
      applied adjuvant HDR 192Ir brachytherapy in 3 male patients with recurrent basal
      cell carcinoma. The average age was 58 years (52 to 75 years). From group of 41
      patients with non melanotic malignant tumors of the eyelids in 3 patients (7.3 %)
      with relapse after incomplete excision of the basal cell carcinoma of the lower
      eyelid we applied after removal of stitches after surgery adjuvant HDR 192Ir
      brachytherapy. For each patient was made individual orfit mask that bore plastic
      applicators. Tungsten eye shield applicator was applied to protect the eye globe.
      Treatment of 10 fractions of 4.5 Gy single dose (5 times weekly) were scheduled
      within 2 weeks. Patients received outpatient treatment. CONCLUSION: Acute
      toxicity postradiation erythema of eyelid and skin around relieved by standard
      symptomatic treatment within a few days after completion of radiation therapy. In
      2 year interval after HDR 192Ir brachytherapy we did not record the occurrence of
      late complications such as corneal ulcers. Our preliminary experience shows
      excellent early skin tolerance. After 2 years of follow-up at 6 month interval we
      did not recognize relapse in our group of patients. The proposed technique of HDR
      192Ir brachytherapy after surgery should be considered a new clinical treatment
      in patients with recurrent non melanotic eyelid cancer. Its main advantage lies
      in the usefulness in all types of basal cell and squamous cell carcinoma and
      sebaceous carcinoma of the eyelids, without restriction by site, dimension,
      clinical or histological type, or the patients general status.

PMID- 23964873
TI  - [Vogt-Koyanagi-Harada syndrome in children - a case report].
AB  - Vogt-Koyanagi-Harada (VKH) syndrome is a multisystemic disease characterized by
      granulomatous panuveitis with exsudative retinal detachment and often associated
      with neurological and skin symptomatology. In the paper is presented a rare case
      of probably VHK syndrome in 11-year old caucasian race boy in which was found the
      bilateral granulomatous panuveitis with exsudative retinal detachment without
      other systemic symptomatology with typical clinical characteristics and course.
      Systemic corticosteroid therapy in a patient gradually improved the state, which
      was then complicated by the occurrence of juxtapapillary subretinal neovascular
      membrane on both eyes. The following administration of intravitreal injection
      anti-VEGF (bevacizumab) was modified visual acuity and reduced neovascular
      membrane. Key words: Vogt-Koyanagi-Harada syndrome, children, juxtapapillary
      choroidal neovascular membrane, anti-VEGF, bevacizumab. 

PMID- 23964874
TI  - [Contraception and ocular thromboembolic episodes - a case report].
AB  - The aim of the paper is to warn of the retinal vein occlusion possibility due to
      the using of hormonal contraceptive pills in young female patients. A case report
      of 22 years old female patient hospitalized at the Department of Ophthalmology,
      School of Medicine, Masaryk University, Brno, Czech Republic, E.U., with sudden
      decrease of the left eye visual acuity is presented. After excluding other causes
      of visual acuity decrease, the diagnosis of prethrombotic state was made and
      anticoagulant treatment was started. Key words: optic disc edema, prethrombotic
      state, retinal vein occlusion, visual acuity decrease, hormonal contraception. 

PMID- 23964875
TI  - Multiple memory systems: what and why.
AB  - Abstract Evidence from a variety of domains converges on the view that there are
      multiple learning/memory systems, but there is no clear understanding of what
      these systems are, and why they should exist. I review an hypothesis about
      multiple memory systems postulated by O'Keefe and Nadel (The hippocampus ac a
      Cognitive map, Oxford: Clarendon Press, 1978), in particular our assertions about
      the nature of two kinds of systems (the locale and taxon systems), and what
      differentiates them from each other. I concentrate on our assumption that systems
      differ in terms of the type of information they process, rather than in terms of
      the temporal duration over which they function. Our "content-driven" dichotomy is
      contrasted with several other current views, none of which appears to explain
      extant data, or provides clear predictions about when one or the other kind of
      system would be engaged. Finally, 1 briefly consider why such distinct systems
      might have evolved. 

PMID- 23964876
TI  - Variations in synaptic plasticity and types of memory in corticohippocampal
      networks.
AB  - Abstract If Synaptic long-term potentiation (LTP) represents a memory storage
      mechanism, its induction and expression characteristics may constitute rules
      governing encoding and read-out of memory in cortical circuitry, The presence of
      variants of the LTP effect in different anatomical networks provides grounds for
      predictions about the types of memory operations to which potentiation
      contributes. Computer modeling studies incorporating the complex rules for LTP
      induction and the characteristics of expressed potentiation can be used to make
      such predictions specific. We review ttie types of synaptic plasticity found in
      the successive stages of the corticohippocampal pathway, and present results
      indicating that LTP does participate in definably different forms of memory,
      suggesting a classification of memory types differing somewhat from categories
      deduced from behavioral studies. Specifically, the results suggest that subtypes
      of memory operate serially, in an "assembly line" of specialized functions, each
      of which adds a unique aspect to the processing of memories. The effects of
      lesions on the encoding versus expression of memory can be interpreted from the
      perspective of this hypothesis. 

PMID- 23964877
TI  - Mnemonic dissociations: the power of parameters.
AB  - Abstract Memory, as reflected in neural plasticity, is certainly not a
      functionally homogeneous process. Within the context of the mnemonic functions of
      the hippocampal system, this paper discusses two issues. The first concerns the
      appropriate conceptual approach to be taken in a neuropsychological analysis of
      memory. We conclude that a dimensional approach, emphasizing a quantitative
      analysis of individual mnemonic processes, has a significant advantage over the
      dichotomous classification of different types of memory. The second issue
      concerns the most appropriate way to describe the role of the hippocampus in
      mnemonic processes. On the basis of electrophysiological, neurochemical,
      behavioral, and computational analyses of hippocampal function, we suggest that
      its major role is the reduction of interference. 

PMID- 23964878
TI  - Configural and elemental associations and the memory coherence problem.
AB  - Abstract Some important empirical findings and theoretical positions that
      interest contemporary students of learning and memory are discussed in the
      context of Luria's (1979) memory coherence perspective. This approach assumes
      that an important challenge to memory function is remaining closed to the
      influence of associations that are extraneous to the demands of the task at hand.
      We argue that the ability to support configural associations between
      representations of the joint occurrence or conjunction of two or more stimulus
      elements and a target memory is an important feature of a closed system but that
      an open system can support only elemental associations with the target.
      Successful performance in many tasks used to study memory can be achieved by
      elemental associations, but other tasks require the formation of and retrieval by
      configural associations. From this perspective, the pattern of spared and
      impaired performance often seen in animals and people with brain damage to the
      hippocampal system or in amnesic people of various etiologies results because
      their memory systems are open and can support only elemental associations. 

PMID- 23964879
TI  - The hippocampal system and declarative memory in animals.
AB  - Abstract Theoretical arguments and empirical data are presented in favor of the
      hypothesis that the hippocampal system supports a declarative memory capacity in
      animals as well as humans. This view is advanced by identifying two prominent
      characteristics of human declarative memory and by operationalizing and
      evaluating them using both experimental lesion and single unit recording studies
      on animals. First, hippocampal processing is not selective to any particular
      category of learning materials; instead, it supports comparisons among all kinds
      of information in memory, resulting in a representation of critical relations
      between items. Conversely, individual representations are supported outside the
      hippocampal system. Second, hippocampal-dependent, relational memory
      representations involve a flexible organization that permits inferences from
      memory in novel situations. Conversely, hippocampal-independent individual
      representations can support only repetition of procedures acquired during
      original learning. Correspondences between the neuropsychological and
      neurophysiological findings presented serve to indicate how these properties of
      hippocampal representation support declarative memory across behavioral paradigms
      and across species. 

PMID- 23964880
TI  - Declarative and nondeclarative memory: multiple brain systems supporting learning
      and memory.
AB  - Abstract The topic of multiple forms of memory is considered from a biological
      point of view. Fact-and-event (declarative, explicit) memory is contrasted with a
      collection of non conscious (non-declarative, implicit) memory abilities
      including skills and habits, priming, and simple conditioning. Recent evidence is
      reviewed indicating that declarative and non declarative forms of memory have
      different operating characteristics and depend on separate brain systems. A brain
      systems framework for understanding memory phenomena is developed in light of
      lesion studies involving rats, monkeys, and humans, as well as recent studies
      with normal humans using the divided visual field technique, event-related
      potentials, and positron emission tomography (PET). 

PMID- 23964881
TI  - Priming and multiple memory systems: perceptual mechanisms of implicit memory.
AB  - Abstract Research examining the relation between explicit and implicit forms of
      memory has generated a great deal of evidence concerning the issue of multiple
      memory systems. This article focuses on an extensively studied implicit memory
      phenomenon, known as direct or repetition priming, and examines the hypothesis
      that priming effects on various tasks reflect the operation of a perceptual
      representation system (PRS)-a class of cortically based subsystems that operate
      at a presemantic level and support non conscious expressions of memory. Three PRS
      subsystems are examined: visual word form, structural description, and auditory
      word form. Pertinent cognitive, neuropsychological, and neurobiological evidence
      is reviewed, alternative classificatory schemes are discussed, and important
      conceptual and terminological issues are considered. 

PMID- 23964882
TI  - Memory and Working-with-Memory: A Component Process Model Based on Modules and
      Central Systems.
AB  - Abstract A neuropsychological model of memory is proposed that incorporates
      Fodor's (1983) idea of modules and central systems. The model has four essential
      components: (1) a non-frontal neocortical component that consists of perceptual
      (and perhaps interpretative semantic) modules that mediate performance on item
      specific, implicit tests of memory, (2) a modular medial temporal/hippocampal
      component that mediates encoding, storage, and retrieval on explicit, episodic
      tests of memory that are associative/cue dependent, (3) a central system, frontal
      lobe component that mediates performance on explicit tests that are strategic and
      on procedural tests that are rule-bound, and (4) a basal ganglia component that
      mediates performance on sensorimotor, procedural tests of memory. The usefulness
      of the modular/central system construct is explored and evidence from studies of
      normal, amnesic, agnosic, and demented people is provided to support the model. 

PMID- 23964883
TI  - MEM: Mechanisms of Recollection.
AB  - Abstract The MEM framework (Johnson, 1991a, b; Johnson & Hirst, 1992; Johnson &
      Multhaup, 1992) consists of a relatively small set of component cognitive
      processes configured into memory subsystems. Here MEM is used to discuss
      "recollection," particularly the mechanisms by which aspects of experience become
      bound together to yield the phenomenal experience of contextually specific, event
      like memories. I consider how central aspects of complex events are bound to each
      other and propose that these same cognitive activities operate to bind central
      and contextual elements into "episodic" memories. Attention is particularly
      focused on the role of reactivation in establishing complex memories and in
      strengthening or consolidating them over time. 

PMID- 23964884
TI  - Working Memory: The Interface between Memory and Cognition.
AB  - Abstract Working memory may be defined as the system for the temporary
      maintenance and manipulation of information, necessary for the performance of
      such complex cognitive activities as comprehension, learning, and reasoning. Used
      in this sense, the term refers to an area of research that may or may not prove
      to be dependent on a single coherent system. Such a system is proposed within a
      broad and relatively speculative overview of human memory that emphasizes the
      putative role of working memory. This is followed by a brief account of a
      particular model of working memory, and a more detailed discussion of the way in
      which the various subcomponents of the model relate to other aspects of memory
      and cognition. 

PMID- 23964885
TI  - Cognitive Binding: A Computational-Modeling Analysis of a Distinction between
      Implicit and Explicit Memory.
AB  - Abstract Four models were compared on repeated explicit memory (fragment cued
      recall) or implicit memory (fragment completion) tasks (Hayman & Tulving, 1989a).
      In the experiments, when given explicit instructions to complete fragments with
      words from a just-studied list-the explicit condition-people showed a dependence
      relation between the first and the second fragment targeted at the same word.
      However, when subjects were just told to complete the (primed) fragments-the
      implicit condition-stochastic independence between the two fragments resulted.
      Three distributed models-CHARM, a competitive-learning model, and a back
      propagation model produced dependence, as in the explicit memory test. In
      contrast, a separate-trace model, MINERVA, showed independence, as in the
      implicit task. It was concluded that explicit memory is based on a highly
      interactive network that glues or binds together the features within the items,
      as do the first three models. The binding accounts for the dependence relation.
      Implicit memory appears to be based, instead, on separate non interacting traces.

PMID- 23964887
TI  - Excitement in dogs recovering from alfaxalone anaesthesia: is the absent drug
      blamed in error?

PMID- 23964888
TI  - Point-of-care tests in general practice: hope or hype?
AB  - Point-of-care tests are biomedical tests on patients' specimens like blood,
      saliva, urine or faeces, which can be used near the patient, without interference
      of a laboratory. The use of these tests, many of which have been recently
      developed, is increasing in general practice, where they add to the GP's set of
      diagnostic instruments. The question is, however, whether they always contribute
      to an effective and high-quality diagnostic process by GPs. We present a set of
      criteria that can be used by guideline developers, regional primary care
      organizations and individual GPs to evaluate a new point-of-care test in a
      practice setting. These criteria do not relate only to their use and quality. A
      point-of-care test needs to be evaluated in the right population and for the
      right indications, and GPs then need to use them for the indications for which
      they were evaluated. Expanding the range of indications can lead to an increase
      in false-positive and false-negative test results.

PMID- 23964889
TI  - Effect of dietary vitamin E on broiler meat qualities, color, water-holding
      capacity and shear force value, under heat stress conditions.
AB  - This study was conducted to evaluate the effect of dietary vitamin E (VE) on
      broiler meat quality, especially focused on PSE (pale color, soft and exudative),
      under chronic heat stress (HS) conditions. Twenty-eight-day-old female Ross
      broilers were kept in independent cages with a controlled temperature of 24
      degrees C (normal temperature: NT) or 30 degrees C (high temperature: HT). The NT
      chickens were fed basal feed. The HT chickens were fed basal feed (HT) or VE (200
      mg/kg) added feed (HT + E). Broilers were weighed and slaughtered at 38 days old.
      The breast muscle was removed immediately and then the samples were used for
      determination of meat color, pH, water holding capacity (WHC) and shear force
      value (SFV). Body weight gain and feed intake were significantly decreased in the
      HT and HT + E groups compared to the NT group. VE supplementation did not affect
      the growth performance. Chronic HS at 30 degrees C for 10 days may cause
      deterioration of meat quality such as PSE. The effects of chronic HS on meat
      quality were most significant in the toughness of broiler breast meat.
      Supplementation of VE in broiler feed would be effective to prevent the extent of
      PSE on broiler meat by chronic HS. 

PMID- 23964892
TI  - Fluorogenic, catalytic, photochemical reaction for amplified detection of nucleic
      acids.
AB  - Photochemical, nucleic acid-induced reactions, which are controlled by nontoxic
      red light, are well-suited for detection of nucleic acids in live cells, since
      they do not require any additives and can be spatially and temporally regulated.
      We have recently described the first reaction of this type, in which a
      phenylselenyl derivative of thymidine (5'-PhSeT-ODNa) is cleaved in the presence
      of singlet oxygen (Fulop, A., Peng, X., Greenberg, M. M., Mokhir, A. (2010) A
      nucleic acid directed, red light-induced chemical reaction. Chem. Commun. 46,
      5659-5661). The latter reagent is produced upon exposure of a photosensitizer 3'
      PS-ODNb (PS = Indium(III)-pyropheophorbide-a-chloride: InPPa) to >630 nm light.
      In 2012 we reported on a fluorogenic version of this reaction (Dutta, S.,
      Flottmann, B., Heilemann, M., Mokhir, A. (2012) Hybridization and reaction-based,
      fluorogenic nucleic acid probes. Chem. Commun. 47, 9664-9666), which is
      potentially applicable for the detection of nucleic acids in cells.
      Unfortunately, its yield does not exceed 25% and no catalytic turnover could be
      observed in the presence of substrate excess. This problem occurs due to the
      efficient, competing oxidation of the substrate containing an electron rich
      carbon-carbon double bonds (SCH?CHS) in the presence of singlet oxygen with
      formation of a noncleavable product (SCH?CHSO). Herein we describe a related, but
      substantially improved photochemical, catalytic transformation of a fluorogenic,
      organic substrate, which consists of 9,10-dialkoxyanthracene linked to
      fluorescein, with formation of a bright fluorescent dye. In highly dilute
      solution this reaction occurs only in the presence of a nucleic acid template. We
      developed three types of such a reaction and demonstrated that they are high
      yielding and generate over 7.7 catalytic turnovers, are sensitive to single
      mismatches in nucleic acid targets, and can be applied for determination of both
      the amount of nucleic acids and potentially their localization. 

PMID- 23964891
TI  - Establishment of feline intestinal epithelial cell cultures for the propagation
      and study of feline enteric coronaviruses.
AB  - Feline infectious peritonitis (FIP) is the most feared infectious cause of death
      in cats, induced by feline infectious peritonitis virus (FIPV). This coronavirus
      is a virulent mutant of the harmless, ubiquitous feline enteric coronavirus
      (FECV). To date, feline coronavirus (FCoV) research has been hampered by the lack
      of susceptible cell lines for the propagation of serotype I FCoVs. In this study,
      long-term feline intestinal epithelial cell cultures were established from
      primary ileocytes and colonocytes by simian virus 40 (SV40) T-antigen- and human
      Telomerase Reverse Transcriptase (hTERT)-induced immortalization. Subsequently,
      these cultures were evaluated for their usability in FCoV research. Firstly, the
      replication capacity of the serotype II strains WSU 79-1683 and WSU 79-1146 was
      studied in the continuous cultures as was done for the primary cultures. In
      accordance with the results obtained in primary cultures, FCoV WSU 79-1683 still
      replicated significantly more efficient compared to FCoV WSU 79-1146 in both
      continuous cultures. In addition, the cultures were inoculated with faecal
      suspensions from healthy cats and with faecal or tissue suspensions from FIP
      cats. The cultures were susceptible to infection with different serotype I
      enteric strains and two of these strains were further propagated. No infection
      was seen in cultures inoculated with FIPV tissue homogenates. In conclusion, a
      new reliable model for FCoV investigation and growth of enteric field strains was
      established. In contrast to FIPV strains, FECVs showed a clear tropism for
      intestinal epithelial cells, giving an explanation for the observation that FECV
      is the main pathotype circulating among cats. 

PMID- 23964890
TI  - Simple biological systems for assessing the activity of superoxide dismutase
      mimics.
AB  - SIGNIFICANCE: Half a century of research provided unambiguous proof that
      superoxide and species derived from it-reactive oxygen species (ROS)-play a
      central role in many diseases and degenerative processes. This stimulated the
      search for pharmaceutical agents that are capable of preventing oxidative damage,
      and methods of assessing their therapeutic potential. RECENT ADVANCES: The
      limitations of superoxide dismutase (SOD) as a therapeutic tool directed
      attention to small molecules, SOD mimics, that are capable of catalytically
      scavenging superoxide. Several groups of compounds, based on either metal
      complexes, including metalloporphyrins, metallocorroles, Mn(II) cyclic
      polyamines, and Mn(III) salen derivatives, or non-metal based compounds, such as
      fullerenes, nitrones, and nitroxides, have been developed and studied in vitro
      and in vivo. Very few entered clinical trials. CRITICAL ISSUES AND FUTURE
      DIRECTIONS: Development of SOD mimics requires in-depth understanding of their
      mechanisms of biological action. Elucidation of both molecular features,
      essential for efficient ROS-scavenging in vivo, and factors limiting the
      potential side effects requires biologically relevant and, at the same time,
      relatively simple testing systems. This review discuses the advantages and
      limitations of genetically engineered SOD-deficient unicellular organisms,
      Escherichia coli and Saccharomyces cerevisiae as tools for investigating the
      efficacy and mechanisms of biological actions of SOD mimics. These simple systems
      allow the scrutiny of the minimal requirements for a functional SOD mimic: the
      association of a high catalytic activity for superoxide dismutation, low
      toxicity, and an efficient cellular uptake/biodistribution.

PMID- 23964893
TI  - Design and in vitro characterization of small unilamellar niosomes as ophthalmic
      carrier of dorzolamide hydrochloride.
AB  - The objective of this work was to formulate and characterize non-ionic surfactant
      vesicles (niosomes) as an ocular carrier of dorzolamide hydrochloride (Dorzo);
      one of the antiglaucoma drugs. Niosomes were prepared of Cholesterol (Chol) with
      sorbitan monoesters (Span 20, 40, 60) or sorbitan trioleate (Span 85) in a molar
      ratio of 40:150. Those prepared from Span 40 were selected for further
      investigation on the effect of addition of dicetylphosphate (DCP) and
      polyoxyethylene fatty acid esters (either Tween 20, 40 or 80). All The batches
      were prepared using mechanical shaking technique, followed by sonication and then
      characterized using Zetasizer, transmission electron microscopy (TEM),
      calculating percent drug entrapment efficiency and cumulative percent released. Z
      average sizes of the niosomes were between 25.9 and 165.5 nm. All niosomal
      formulations showed negative zeta potential charge. Dorzo was successfully
      entrapped in all of the formulations with entrapment efficiencies ranging between
      34.81% and 97.66%. With reference to release profiles, Dorzo-loaded niosomal
      formulations showed significant reduction in cumulative percent drug released
      than Dorzo solution. High entrapment efficiencies, biphasic prolonged release
      rate and small particles size highlight Dorzo-loaded niosomal preparations as a
      promising ophthalmic carrier to prolong the drug lowering effect on the
      intraocular pressure.

PMID- 23964894
TI  - Electronic quenching of OH A 2Sigma+ induced by collisions with Kr atoms.
AB  - Electronic quenching of OH A (2)Sigma(+) by Kr was investigated through
      experimental studies of the collision cross sections and the OH X (2)Pi product
      state distribution. The quenching cross sections decrease with increasing
      rotational excitation in the excited OH A (2)Sigma(+) electronic state. The OH X
      (2)Pi products of quenching exhibit a significant degree of rotational excitation
      but minimal vibrational excitation. Complementary theoretical studies of the OH
      (A (2)Sigma(+), X (2)Pi) + Kr potential energy surfaces (PESs), nonadiabatic
      coupling, and quasiclassical trajectory calculations were carried out to
      elucidate the quenching dynamics. Accurate PESs for the two lowest diabatic
      states of A' symmetry were computed along with the angularly dependent coupling
      between them. Coupling in nearly linear HO-Kr configurations provides the
      mechanism for the observed electronic quenching. A deep attractive well on the OH
      A (2)Sigma(+) + Kr PES facilitates access to this region of strong coupling.
      Surface-hopping quasiclassical trajectory calculations yielded quenching cross
      sections and a OH X (2)Pi product rotational distribution in good accord with
      experimental observations. 

PMID- 23964895
TI  - Differences in skin microcirculation on the upper and lower extremities in
      patients with diabetes mellitus: relationship of diabetic neuropathy and skin
      microcirculation.
AB  - INTRODUCTION: During recent years, the role of microcirculation has received
      increasing attention especially for its potential pathogenic role in the
      development of diabetes complications, particularly diabetic foot syndrome. The
      aim of this study was to evaluate the differences in the skin microcirculatory
      reactivity on the upper and lower extremities (UE and LE, respectively) in the
      patient with type 2 diabetes mellitus (T2DM). We also evaluated the changes in
      the skin microcirculation independently of the individual test for peripheral
      diabetic neuropathy (DN) diagnosis (Semmes-Weinstein monofilaments, Bio
      Thesiometer [Bio-Medical Instrument Co., Newbury, OH], and Neuropad((r))
      [TRIGOcare International GmbH, Wiehl, Germany]). PATIENTS AND METHODS: Fifty-two
      patients with T2DM were enrolled. Microvascular reactivity was measured by laser
      Doppler iontophoresis, using 1% acetylcholine chloride (ACH) and 1% sodium
      nitroprusside. RESULTS: Significant reduction of perfusion was found in LE
      compared with UE when using ACH. In patients with DN skin microvascular
      reactivity on LE and UE was reduced, compared with patients without DN. Impaired
      skin microvascular reactivity to ACH (dominant on LE) was demonstrated in all
      patients who were positive in at least one of the tests for the presence of DN.
      CONCLUSIONS: Reactivity of the skin microcirculation is worse on the foot than on
      the hand. This study confirmed a close relationship of DN and impaired skin
      microcirculation. It seems that autonomous neuropathy (assessed using the
      Neuropad) precedes the manifestation of somatosensory neuropathy.

PMID- 23964896
TI  - Panx1 regulates neural stem and progenitor cell behaviours associated with
      cytoskeletal dynamics and interacts with multiple cytoskeletal elements.
AB  - BACKGROUND: Pannexins (Panxs) are relatively newly discovered large-pore ion and
      metabolite permeable channels. Although no proteomics-based interactome has yet
      been published, Panx1 has been demonstrated to interact with actin in an ectopic
      expression system. This interaction affects both Panx1 plasma membrane stability
      as well as cytoskeletal remodelling. The current study builds on our recent
      discovery of Panx1 expression in ventricular zone (VZ) neural stem and progenitor
      cells (NSC/NPCs), and on the demonstrated interaction of Panx1 with the
      cytoskeleton. FINDINGS: Here we demonstrate that Panx1 also plays roles in two
      additional cell behaviours associated with neurogenesis, including cell migration
      and neurite extension. Furthermore, we confirm an endogenous interaction between
      actin and Panx1, and identify a new interaction with actin-related protein 3, an
      actin cytoskeleton-modulating protein. CONCLUSIONS: This study further
      establishes the importance of Panx1 in the cell biology of NSC/NPCs and
      strengthens and expands our knowledge of Panx1 interactions with the
      cytoskeleton.

PMID- 23964897
TI  - Abusive prescribing of controlled substances--a pharmacy view.

PMID- 23964898
TI  - Risks (and benefits) in comparative effectiveness research trials.

PMID- 23964899
TI  - Polymer crystallization as a tool to pattern hybrid nanostructures: growth of 12
      nm ZnO arrays in poly(3-hexylthiophene).
AB  - Well-ordered hybrid materials with a 10 nm length scale are highly desired. We
      make use of the natural length scale (typically 10-15 nm) of the alternating
      crystalline and amorphous layers that are generally found in semicrystalline
      polymers to direct the growth of a semiconducting metal oxide. This approach is
      exemplified with the growth of ZnO within a carboxylic acid end-functionalized
      poly(3-hexylthiophene) (P3HT-COOH). The metal-oxide precursor vapors diffuse into
      the amorphous parts of the semicrystalline polymer so that sheets of ZnO up to
      0.5 MUm in size can be grown. This P3HT-ZnO nanostructure further functions as a
      donor-acceptor photovoltaic system, with length scales appropriate for charge
      photogeneration. 

PMID- 23964900
TI  - Dechlorination of commercial PCBs and other multiple halogenated compounds by a
      sediment-free culture containing Dehalococcoides and Dehalobacter.
AB  - At the contaminated sites, polychlorinated biphenyls (PCBs) frequently coexist
      with other halogenated compounds, such as polybrominated diphenyl ethers (PBDEs),
      chloroethanes, and chloroethenes. The presence of multiple halogenated compounds
      usually poses toxicity to dehalogenating microbes, because few cultures are
      capable of detoxifying a broad spectrum of halogenated compounds. In this study,
      a sediment-free culture, designed as AD14, is able to sequentially remove
      halogens from PCBs and other cocontaminants. Culture AD14 dechlorinated the
      commercial PCB mixture-Aroclor 1260-mainly by removing flanked para- and doubly
      flanked meta-chlorines. It also dehalogenated octa-brominated diphenyl ether
      mixture predominantly to tetra-BDEs, 2,4,6-trichlorophenol (2,4,6-TCP) to 4-CP,
      and tetrachloroethene (PCE)/1,2-dichloroethane (1,2-DCA) completely to ethene.
      When applied to a mixture of the above-mentioned compounds, culture AD14 stepwise
      removed halogens from 2,4,6-TCP, 1,2-DCA, PCE, PBDEs, and PCBs. Illumina
      sequencing analysis of 16S rRNA genes showed that only two known dechlorinating
      genera, Dehalococcoides and Dehalobacter, were present in culture AD14.
      Quantitative real-time PCR analysis showed that the 16S rRNA gene copies of
      Dehalococcoides and Dehalobacter increased from 1.14 * 10(5) to 7.04 * 10(6)
      copies mL(-1) and from 1.15 * 10(5) to 8.20 * 10(6) copies mL(-1) after removing
      41.13 MUM of total chlorine from PCBs. The above results suggest that both
      Dehalobacter and Dehalococcoides could be responsible for PCB dechlorination.
      Although two Dehalococoides mccartyi strains with identical 16S rRNA genes were
      isolated from the PCBs-dechlorinating mixed culture using trichloroethene (TCE)
      and vinyl chloride (VC) as alternatives to PCBs, the two isolates are incapable
      of dechlorinating PCBs. In all, culture AD14 is promising for bioremediation
      applications at sites cocontaminated with PCBs and other halogenated compounds. 

PMID- 23964901
TI  - Structure of the sigma1 receptor and its ligand binding site.
AB  - The exact 3D structure of the enigmatic sigma1 receptor is unknown, as the
      crystal structure of this protein has not been solved so far. Many efforts have
      been devoted to unveiling the structure of the sigma1 receptor and specifically
      its binding site, which include photoaffinity labeling, site directed
      mutagenesis, and homology modeling. The aim of the present miniperspective is to
      give a short overview of all results that contribute to the current knowledge of
      the sigma1 receptor and its ligand binding site.

PMID- 23964902
TI  - The homeodomain-leucine zipper ATHB23, a phytochrome B-interacting protein, is
      important for phytochrome B-mediated red light signaling.
AB  - Phytochromes are red (R)/far-red (FR) photoreceptors that are central to the
      regulation of plant growth and development. Although it is well known that
      photoactivated phytochromes are translocated into the nucleus where they interact
      with a variety of nuclear proteins and ultimately regulate genome-wide
      transcription, the mechanisms by which these photoreceptors function are not
      completely understood. In an effort to enhance our understanding of phytochrome
      mediated light signaling networks, we attempted to identify novel proteins
      interacting with phytochrome B (phyB). Using affinity purification in Arabidopsis
      phyB overexpressor, coupled with mass spectrometry analysis, 16 proteins that
      interact with phyB in vivo were identified. Interactions between phyB and six
      putative phyB-interacting proteins were confirmed by bimolecular fluorescence
      complementation (BiFC) analysis. Involvement of these proteins in phyB-mediated
      signaling pathways was also revealed by physiological analysis of the mutants
      defective in each phyB-interacting protein. We further characterized the athb23
      mutant impaired in the homeobox protein 23 (ATHB23) gene. The athb23 mutant
      displayed altered hypocotyl growth under R light, as well as defects in phyB
      dependent seed germination and phyB-mediated cotyledon expansion. Taken together,
      these results suggest that the ATHB23 transcription factor is a novel component
      of the phyB-mediated R light signaling pathway.

PMID- 23964903
TI  - Novel bioinformatics strategies for prediction of directional sequence changes in
      influenza virus genomes and for surveillance of potentially hazardous strains.
AB  - BACKGROUND: With the remarkable increase of microbial and viral sequence data
      obtained from high-throughput DNA sequencers, novel tools are needed for
      comprehensive analysis of the big sequence data. We have developed "Batch
      Learning Self-Organizing Map (BLSOM)" which can characterize very many, even
      millions of, genomic sequences on one plane. Influenza virus is one of zoonotic
      viruses and shows clear host tropism. Important issues for bioinformatics studies
      of influenza viruses are prediction of genomic sequence changes in the near
      future and surveillance of potentially hazardous strains. METHODS: To
      characterize sequence changes in influenza virus genomes after invasion into
      humans from other animal hosts, we applied BLSOMs to analyses of mono-, di-, tri
      , and tetranucleotide compositions in all genome sequences of influenza A and B
      viruses and found clear host-dependent clustering (self-organization) of the
      sequences. RESULTS: Viruses isolated from humans and birds differed in
      mononucleotide composition from each other. In addition, host-dependent
      oligonucleotide compositions that could not be explained with the host-dependent
      mononucleotide composition were revealed by oligonucleotide BLSOMs. Retrospective
      time-dependent directional changes of mono- and oligonucleotide compositions,
      which were visualized for human strains on BLSOMs, could provide predictive
      information about sequence changes in newly invaded viruses from other animal
      hosts (e.g. the swine-derived pandemic H1N1/09). CONCLUSIONS: Basing on the host
      dependent oligonucleotide composition, we proposed a strategy for prediction of
      directional changes of virus sequences and for surveillance of potentially
      hazardous strains when introduced into human populations from non-human sources.
      Millions of genomic sequences from infectious microbes and viruses have become
      available because of their medical and social importance, and BLSOM can
      characterize the big data and support efficient knowledge discovery.

PMID- 23964904
TI  - Reciprocal relationship between plasma ghrelin level and arterial stiffness in
      hypertensive subjects.
AB  - Arterial stiffness, considered an independent predictor of cardiovascular
      morbidity and mortality, is closely associated with hypertension. Futhermore, the
      role of ghrelin in the development of hypertension has been widely recognized.
      The purpose of the present study was to explore the potential relationship
      between circulating ghrelin and arterial stiffness in hypertensive subjects. A
      total of 192 patients with primary hypertension and 107 normotensive (NT) control
      subjects were enrolled in the present cross-sectional study. Plasma ghrelin was
      determined by ELISA. Arterial stiffness was assessed by brachial-ankle pulse wave
      velocity (baPWV) and the augmentation index (AIx). Both baPWV and AIx values were
      markedly higher in the hypertensive compared with NT group (P < 0.01). In
      contrast, plasma ghrelin concentrations were significantly lower in hypertensive
      patients compared with NT subjects (P < 0.01). Plasma ghrelin concentrations were
      negatively correlated with age (odds ratio (OR) -1.836; P < 0.001), smoking (OR 
      1.347; P = 0.042), baPWV (OR -1.762; P < 0.001) and AIx (OR -1.516; P = 0.005),
      but positively associated with fasting plasma glucose (OR 1.293; P = 0.047) and
      HbA1c (OR 1.413; P = 0.025). The inverse correlation between circulating ghrelin
      and the extent of arterial stiffness suggests that ghrelin is an independent
      determinant of arterial stiffness, even after adjustment for confounding
      cardiovascular risk factors, and it actively participates in the pathophysiology
      of arterial stiffness in hypertensive subjects.

PMID- 23964905
TI  - Regional health care planning: a methodology to cluster facilities using
      community utilization patterns.
AB  - BACKGROUND: Community-based health care planning and regulation necessitates
      grouping facilities and areal units into regions of similar health care use.
      Limited research has explored the methodologies used in creating these regions.
      We offer a new methodology that clusters facilities based on similarities in
      patient utilization patterns and geographic location. Our case study focused on
      Hospital Groups in Michigan, the allocation units used for predicting future
      inpatient hospital bed demand in the state's Bed Need Methodology. The
      scientific, practical, and political concerns that were considered throughout the
      formulation and development of the methodology are detailed. METHODS: The
      clustering methodology employs a 2-step K-means + Ward's clustering algorithm to
      group hospitals. The final number of clusters is selected using a heuristic that
      integrates both a statistical-based measure of cluster fit and characteristics of
      the resulting Hospital Groups. RESULTS: Using recent hospital utilization data,
      the clustering methodology identified 33 Hospital Groups in Michigan.
      CONCLUSIONS: Despite being developed within the politically charged climate of
      Certificate of Need regulation, we have provided an objective, replicable, and
      sustainable methodology to create Hospital Groups. Because the methodology is
      built upon theoretically sound principles of clustering analysis and health care
      service utilization, it is highly transferable across applications and suitable
      for grouping facilities or areal units.

PMID- 23964907
TI  - Cellular retinaldehyde binding protein-different binding modes and micro
      solvation patterns for high-affinity 9-cis- and 11-cis-retinal substrates.
AB  - We use molecular dynamics (MD) simulations to determine the binding properties of
      different retinoid species to cellular retinaldehyde binding protein (CRALBP).
      The complexes formed by 9-cis-retinal or 11-cis-retinal bound to both the native
      protein and the R234W mutant, associated to Bothnia-retina dystrophy, are
      investigated. The presented studies are also complemented by analysis of the
      binding structures of the CRALBP/9-cis-retinol and CRALBP/9,13-dicis-retinal
      complexes. We find that the poor X-ray scattering properties of the polyene tail
      of the ligand in all wild-type complexes can be attributed to a high mobility of
      this region, which does not localize in a single binding conformation even at
      very low temperatures. Our simulations report a clear difference in the residual
      solvation pattern in CRALBP complexes with either 9-cis- or 9,13-dicis-retinal.
      The reported structures indicate that the microsolvation properties of the ligand
      are the key structural element triggering the very recently discovered isomerase
      activity of this protein. The binding geometries obtained by MD simulations are
      validated by calculation of the respective optical spectra by the ZINDO/S
      semiempirical method, which can reproduce with good qualitative agreement the
      different red-shifts of the first absorption band of the different complexes. 

PMID- 23964908
TI  - [Polymerase chain reaction: basic principles and applications in molecular
      pathology].
AB  - Polymerase chain reaction (PCR) is a technology used for quick and easy
      amplifying DNA sequences, which is based on the principle of enzymatic
      replication of the nucleic acids. This method has in the field of molecular
      biology an irreplaceable role and constitutes one of the basic methods for DNA
      analysis. In the following article we describe the basic principles of PCR, and
      its importance especially in the field of pathology.

PMID- 23964909
TI  - [Sequencing - classical method].
AB  - In this article the basic methods of reading nucleotide sequences in DNA
      molecules are summarized. Sanger sequencing is described most thoroughly as it is
      the most frequent routine method currently being utilized. The article describes
      in detail the principle of sequence determination through the production of
      fragments with a known end base using chain termination synthesis of DNA and ways
      of separation and detection of the fragments. Some alternative methods of
      sequencing are mentioned in short. Basic approaches of analyzing sequence data
      are explained as well as different outcomes, obstacles and challenges.

PMID- 23964910
TI  - [Next-generation sequencing].
AB  - Next generation or massive parallel sequencing (MPS) is a rapidly advancing
      method in molecular genetics that will bring significant changes in the
      personalized medicine field. In this review we briefly describe major types of
      MPS, including whole-genome, -exome, -transcriptome and amplicon sequencing. We
      also present an overview of the advantages, drawbacks and possible applications
      of sequencing technologies available in the Czech Republic.

PMID- 23964911
TI  - Endometriosis in a mesothelial cyst of tunica vaginalis of the testis. Report of
      a case.
AB  - A rare case of endometriosis occurring in paratesticular mesothelial cyst is
      presented. It was found in a 7 mm mesothelial inclusion cyst of tunica vaginalis
      in a 46-years-old old man who underwent a radical orchiectomy for seminoma. It
      showed a typical histologic pattern with endometrioid cylindrical epithelium and
      cellular stroma. The lesion was immunohistochemically positive for estrogen
      receptors and progesterone receptors, in contrast with the adjacent mesothelium.
      However, rare endometrioid epithelial cells expressed mesothelial markers
      calretinin and cytokeratin 5/6. This immunohistochemical overlap with mesothelium
      and morphological transition between endometrioid epithelium and mesothelium
      favor metaplastic pathogenesis of the lesion. In differential diagnosis, it is
      important to distinguish paratesticular endometriosis from tissue of teratoma
      (especially when a germ cell tumor is present in the testis, as was seen in this
      case).

PMID- 23964913
TI  - [Giant cell interstitial pneumonia without exposure to hard metals].
AB  - We describe the case of a 58-year-old woman with giant cell interstitial
      pneumonia without any history of exposure to hard metals. Giant cell interstitial
      pneumonia (GIP) is a rare interstitial lung disease characterized by the presence
      of numerous multinucleated giant cells in the alveolar spaces. Currently GIP is
      regarded as secondary interstitial pneumonia. While it has become almost
      synonymous with hard metal lung disease (cobalt pneumonitis), the literature has
      also included sporadic cases of GIP without exposure to hard metals. This fact
      undermines the synonymical relationship between GIP and hard metal lung disease.
      The alteration of lung tissue in GIP is immunologically mediated. In our patient
      we found a classical histological picture of GIP with lymphoid hyperplasia. At
      the time of diagnosis she was being treated for Hashimoto's thyreoiditis. Later,
      autoimmune hemolytic anemia and bronchial asthma developed. We suggest that our
      case supports the hypothesis of the autoimmune ethiology of idiopathic GIPs.

PMID- 23964912
TI  - [False aneurysm of the wall of a venous graft in a patient with an implanted
      MGuard type of coronary stent: case report and description of the microscopic
      changes].
AB  - The present case report demonstrates a development of a false aneurysm in a
      venous coronary bypass graft wall, which developed at the previous MGuard stent
      implantation area in a 67-year-old patient. Subsequent histological examination
      revealed a false aneurysm image, without detection of vascular wall layers in its
      wall. Microscopically mild neointimal proliferation within the stent was also
      detected, with a strong granulomatous inflammatory reaction, mostly focused on
      the PET fibre mesh present on the surface of the stent. This article demonstrates
      the need for a multidisciplinary approach in dealing with pathological changes in
      stented blood vessels; the authors would also like to remind the public of the
      possibility of histological examination of stented vessels in the Czech Republic.

PMID- 23964914
TI  - The role of repetition and associative interference in new semantic learning in
      amnesia: a case experiment.
AB  - Abstract The question of whether globally amnesic subjects can learn new semantic
      (factual) information is controversial. Some students of amnesia believe that
      they can, others that they cannot. In this article we report an extensive
      experiment conducted with the amnesic patient K.C. in which we examined the role
      of repetition and associative interference in his learning of new semantic
      information. In the course of 8 study sessions distributed over 4 weeks, we
      taught K.C. novel, amusing definitions of 96 target words (e.g., "a talkative
      featherbrain-PARAKEET"). We varied systematically the degree of both pre
      experimental and intraexperimental associative interference, as well as the
      amount of study. The results of the experiment showed that K.C. can learn new
      semantic knowledge, and retain it over a period as long as 30 months
      indistinguishably from control subjects. The results further showed that the
      efficacy of such learning depends critically on both repetition of the material
      and the absence, or minimization, of pre-experimental and intraexperimental
      associative interference. These findings suggest that the extent to which at
      least some amnesic patients can acquire and retain new semantic knowledge depends
      on the conditions under which learning occurs, and that unqualified statements
      regarding the deficiency or absence of such learning in amnesia are not
      justified. 

PMID- 23964915
TI  - Development of elementary numerical abilities: a neuronal model.
AB  - Abstract Despite their lack of language, human infants and several animal species
      possess some elementary abilities for numerical processing. These include the
      ability to recognize that a given numerosity is being presented visually or
      auditorily, and, at a later stage of development, the ability to compare two nume
      rosities and to decide which is larger. We propose a model for the development of
      these abilities in a formal neuronal network. Initially, the model is equipped
      only with unordered numerosity detectors. It can therefore detect the numerosity
      of an input set and can be conditioned to react accordingly. In a later stage,
      the addition of a short-term memory network is shown to be sufficient for number
      comparison abilities to develop. Our computer simulations account for several
      phenomena in the numerical domain, including the distance effect and Fechner's
      law for numbers. They also demonstrate that infants' numerosity detection
      abilities may be explained without assuming that infants can count. The
      neurobiological bases of the critical components of the model are discussed. 

PMID- 23964916
TI  - A self-organizing neural model of motor equivalent reaching and tool use by a
      multijoint arm.
AB  - Abstract This paper describes a self-organizing neural model for eye-hand
      coordination. Called the DIRECT model, it embodies a solution of the classical
      motor equivalence problem. Motor equivalence computations allow humans and other
      animals to flexibly employ an arm with more degrees of freedom than the space in
      which it moves to carry out spatially defined tasks under conditions that may
      require novel joint configurations. During a motor babbling phase, the model
      endogenously generates movement commands that activate the correlated visual,
      spatial, and motor information that are used to learn its internal coordinate
      transformations. After learning occurs, the model is capable of controlling
      reaching movements of the arm to prescribed spatial targets using many different
      combinations of joints. When allowed visual feedback, the model can automatically
      perform, without additional learning, reaches with tools of variable lengths,
      with clamped joints, with distortions of visual input by a prism, and with
      unexpected perturbations. These compensatory computations occur within a single
      accurate reaching movement. No corrective movements are needed. Blind reaches
      using internal feedback have also been simulated. The model achieves its
      competence by transforming visual information about target position and end
      effector position in 3-D space into a body-centered spatial representation of the
      direction in 3-D space that the end effector must move to contact the target. The
      spatial direction vector is adaptively transformed into a motor direction vector,
      which represents the joint rotations that move the end effector in the desired
      spatial direction from the present arm configuration. Properties of the model are
      compared with psychophysical data on human reaching movements, neurophysiological
      data on the tuning curves of neurons in the monkey motor cortex, and alternative
      models of movement control. 

PMID- 23964917
TI  - Visual search for feature and conjunction targets with an attention deficit.
AB  - Abstract Brain-damaged subjects who had previously been identified as suffering
      from a visual attention deficit for contralesional stimulation were tested on a
      series of visual search tasks. The experiments examined the hypothesis that the
      processing of single features is preattentive but that feature integration,
      necessary for the correct perception of conjunctions of features, requires
      attention (Treisman & Gelade, 1980 Treisman & Sato, 1990). Subjects searched for
      a feature target (orientation or color) or for a conjunction target (orientation
      and color) in unilateral displays in which the number of items presented was
      variable. Ocular fixation was controlled so that trials on which eye movements
      occurred were cancelled. While brain-damaged subjects with a visual attention
      disorder (VAD subjects) performed similarly to normal controls in feature search
      tasks, they showed a marked deficit in conjunction search. Specifically, VAD
      subjects exhibited an important reduction of their serial search rates for a
      conjunction target with contralesional displays. In support of Treisman's feature
      integration theory, a visual attention deficit leads to a marked impairment in
      feature integration whereas it does not appear to affect feature encoding. 

PMID- 23964918
TI  - Visual extinction and stimulus repetition.
AB  - Abstract Five patients with visual extinction following unilateral brain injury
      were briefly presented with colored letters in either or both visual fields, and
      required to report and locate the colors or the shapes. On double simultaneous
      stimulation, they tended to miss the event contralateral to their lesion. This
      extinction was increased when the two stimuli were the same on the reported
      dimension, Similarity on the irrelevant dimension had no effect. These data
      suggest that extinguished colors and shapes may be correctly extracted by the
      visual system (when task-relaant) even though they are unavailable for verbal
      report. An analogy is made with the phenomena of "repetition blindness" in normal
      observers, and it is proposed that extinction may reflect failure in a token
      individuation process for correctly extracted visual types. 

PMID- 23964919
TI  - The cortical representation of speech.
AB  - Abstract In this study, we compare regional cerebral blood flow (rCBF) while
      French monolingual subjects listen to continuous speech in an unknown language,
      to lists of French words, or to meaningful and distorted stories in French. Our
      results show that, in addition to regions devoted to single-word comprehension,
      processing of meaningful stories activates the left middle temporal gyrus, the
      left and right temporal poles, and a superior prefrontal area in the left frontal
      lobe. Among these regions, only the temporal poles remain activated whenever
      sentences with acceptable syntax and prosody are presented. 

PMID- 23964920
TI  - Cognitive and physiological substrates of impaired sentence processing in
      Parkinson's disease.
AB  - Abstract Sentence comprehension is a complex process involving at least a
      grammatical processor and a procedural component that supports language
      computations. One type of cerebral architecture that may underlie sentence
      processing is a network of distributed brain regions. We report two experiments
      designed to evaluate the cognitive and physiological substrate of sentence
      processing diaculties in nondemented patients with Parkinson's disease (PD). In
      the first experiment, patients answered simple questions about sentences that
      varied in their computational demands. Group and individual patient analyses
      indicated that PD patients are significantly compromised on this task, and that
      their difficulties become more prominent as the computational demands of the
      sentences increase. We manipulated the set of sentences to stress performance
      aspects of sentence processing. PD patients were compromised in their ability to
      detect errors in the presence and nature of a sentence's grammatical morphemes,
      suggesting a deficit in selective attention, but their ability to answer
      questions about a sentence was not afFected by short-term memory factors. In the
      second experiment, positron emission tomography was used to correlate this
      pattern of sentence comprehension impairment with regional cerebral glucose
      metabolism (rCMRgl) obtained at rest in a representative subset of these PD
      patients. Grammatical comprehension and attention in sentence processing
      correlated significantly with mesial frontal rCMRgl. Regression analyses
      confirmed the central role of left mesial frontal cortex, and identified a
      subsidiary role for left caudate in overall sentence comprehension, for left
      dorsolateral frontal cortex in grammatical processing, and for bilateral
      dorsolateral frontal cortex in attending to the presence of grammatical features.
      We conclude that compromised mesial frontal functioning underlies in part the
      sentence processing deficit of these patients, and these data illustrate one
      method for mapping portions of a sentence processing mechanism onto a distributed
      cerebral architecture. 

PMID- 23964921
TI  - The sexual brain.

PMID- 23964922
TI  - An analysis of the efficacy, safety, and cost-effectiveness of fulguration under
      local anesthesia for small-sized recurrent masses: a comparative analysis to
      transurethral resection of bladder tumors in a matched cohort.
AB  - BACKGROUND AND PURPOSE: To investigate the efficacy, safety, and cost
      effectiveness of fulguration compared with traditional transurethral resection of
      a bladder tumor (TURB) among patients who had recurrent lesions after an initial
      TURB due to bladder cancer. PATIENTS AND METHODS: For the period from March 2001
      to January 2012, we reviewed the records of 42 patients who underwent a
      fulguration procedure for a recurrent Ta small bladder mass after excluding those
      with >=1-cm sized masses at recurrence and those with masses at more than three
      sites. The included fulguration patients were matched with 42 TURB patients who
      presented with similar preoperative factors. The perioperative outcomes,
      including complications, recurrence-free survival rate, and total medical cost
      during each procedure, were compared. RESULTS: The mean tumor size was similar
      between the two groups (0.54 cm in the fulguration group vs. 0.61 cm in the TURB
      group, p=0.161). During the follow-up periods, 12 patients (28.5%) in the
      fulguration group and 11 patients (26.2%) in the TURB group experienced tumor
      recurrence. The recurrence-free survival rate was similar for both groups
      (p=0.880). The mean total medical cost of fulguration was much cheaper compared
      with the TURB group (393.3 vs. 1164.6 US dollars, p<0.001). CONCLUSIONS:
      Fulguration under local anesthesia for a small-sized recurrent mass is safe and
      efficacious in properly selected patients. In addition, it also significantly
      reduces the medical cost and avoids unnecessary anesthesia. Although the two
      treatments yielded similar oncological results, this finding should be validated
      in a large-scale, well-designed prospective study.

PMID- 23964923
TI  - Dose-dependent differential effects of thrombin in allergic bronchial asthma.
AB  - BACKGROUND: Apart from its role in the coagulation system, thrombin plays an
      important role in the inflammatory response through its protease-activated
      receptors (PARs). However, the role of thrombin in the immune response is not
      clear. OBJECTIVE: To evaluate whether thrombin has a modulatory role in allergic
      bronchial asthma. METHODS: Bronchial asthma was induced in mice by
      intraperitoneal sensitization and inhalation challenge with ovalbumin. Thrombin
      or its inhibitors were administered by inhalation before each allergen challenge.
      RESULTS: Mice with low but sustained coagulation activation had reduced allergic
      inflammation, and allergic asthma was inhibited by low doses of thrombin but
      worsened by high doses. Allergic asthma was worsened by antithrombin, argatroban,
      hirudin, and anti-thrombomodulin antibody. Mice with a higher level of an
      inhibitor of both thrombin and activated protein C had worse disease.
      Heterozygous PAR-1 mice had less allergic inflammation, but PAR-1 agonist
      worsened it. Allergic bronchial inflammation was worsened in mice that received
      adoptive transfer of PAR-1 agonist-treated Th2 cells as compared with controls.
      Low levels of thrombin suppressed the maturation and secretion of cytokines in
      dendritic cells, but high levels enhanced this. CONCLUSIONS: The effects of
      thrombin on allergic asthma are dose-dependent, with detrimental effects at high
      doses and protective effects at low doses. These data demonstrate that thrombin
      modulates the outcome in allergic bronchial asthma.

PMID- 23964925
TI  - Association of nicotinamide-N-methyltransferase gene rs694539 variant with
      patients with nonalcoholic steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal
      hepatic steatosis in the absence of a history of alcohol use and with a
      prevalence of 15%-45% in developed nations. Nonalcoholic steatohepatitis (NASH)
      is an advanced stage of NAFLD with a pronounced major inflammatory component. The
      aim of this study was to investigate the possible role of nicotinamide-N
      methyltransferase (NNMT) gene rs694539 variant in the development of NASH.
      Therefore, we analyzed 80 NASH patients and 183 healthy controls using a
      polymerase chain reaction-restriction fragment length polymorphism method
      developed in our laboratory. The NNMT rs694539 variant was found to be
      significantly associated with NASH (chi(2)=9.349, p=0.009). The individuals with
      the GG genotype had protection against NASH (chi(2)=3.793, p=0.051, odds ratio
      [OR]=0.580, 95% confidence interval [CI]=0.334-1.006), whereas the individuals
      with the AA genotype showed statistically significant increased risk for NASH
      (chi(2)=7.748, p=0.005, OR=7.338, 95% CI=1.448-37.190). Moreover, the G allele
      was protective against NASH (chi(2)=7.748, p=0.005, OR=0.136, and 95% CI=0.027
      0.691). On the other hand, the A allele was a risk factor for NASH (chi(2)=3.793,
      p=0.051, OR=1.725, and 95% CI=0.994-2.996). Consequently, the rs694539 variant of
      NNMT gene is a genetic risk factor for developing NASH. 

PMID- 23964924
TI  - Manganese superoxide dismutase is a promising target for enhancing
      chemosensitivity of basal-like breast carcinoma.
AB  - AIMS: Although earlier reports highlighted a tumor suppressor role for manganese
      superoxide dismutase (MnSOD), recent evidence indicates increased expression in a
      variety of human cancers including aggressive breast carcinoma. In the present
      article, we hypothesized that MnSOD expression is significantly amplified in the
      aggressive breast carcinoma basal subtype, and targeting MnSOD could be an
      attractive strategy for enhancing chemosensitivity of this highly aggressive
      breast cancer subtype. RESULTS: Using MDA-MB-231 and BT549 as a model of basal
      breast cancer cell lines, we show that knockdown of MnSOD decreased the colony
      forming ability and sensitized the cells to drug-induced cell death, while drug
      resistance was associated with increased MnSOD expression. In an attempt to
      develop a clinically relevant approach to down-regulate MnSOD expression in
      patients with basal breast carcinoma, we employed activation of the peroxisome
      proliferator-activated receptor gamma (PPARgamma) to repress MnSOD expression;
      PPARgamma activation significantly reduced MnSOD expression, increased
      chemosensitivity, and inhibited tumor growth. Moreover, as a proof of concept for
      the clinical use of PPARgamma agonists to decrease MnSOD expression, biopsies
      derived from breast cancer patients who had received synthetic PPARgamma ligands
      as anti-diabetic therapy had significantly reduced MnSOD expression. Finally, we
      provide evidence to implicate peroxynitrite as the mechanism involved in the
      increased sensitivity to chemotherapy induced by MnSOD repression. INNOVATION AND
      CONCLUSION: These data provide evidence to link increased MnSOD expression with
      the aggressive basal breast cancer, and underscore the judicious use of PPARgamma
      ligands for specifically down-regulating MnSOD to increase the chemosensitivity
      of this subtype of breast carcinoma.

PMID- 23964926
TI  - Acute exacerbations in patients with idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial lung
      disease that primarily affects older adults. Median survival after diagnosis is 2
      3 years. The clinical course of IPF may include periods of acute deterioration in
      respiratory function, which are termed acute exacerbations of IPF (AEx-IPF) when
      a cause cannot be identified. AEx-IPF may represent a sudden acceleration of the
      underlying disease process of IPF, or a biologically distinct pathological
      process that is clinically undiagnosed. An AEx-IPF can occur at any time during
      the course of IPF and may be the presenting manifestation. The incidence of AEx
      IPF is hard to establish due to variation in the methodology used to assess AEx
      IPF in different studies, but AEx-IPF are believed to occur in between 5 and 10%
      of patients with IPF every year. Risk factors for AEx-IPF are unclear, but there
      is evidence that poorer lung function increases the risk of an AEx-IPF and
      reduces the chances of a patient surviving an AEx-IPF. The presence of
      comorbidities such as gastroesophageal reflux disease (GERD) and pulmonary
      hypertension may also increase the risk of an AEx-IPF. AEx-IPF are associated
      with high morbidity and mortality. Patients who experience an AEx-IPF show a
      worsened prognosis and AEx-IPF are believed to reflect disease progression in
      IPF. Current treatments for AEx-IPF have only limited data to support their
      effectiveness. The latest international treatment guidelines state that
      supportive care remains the mainstay of treatment for AEx-IPF, but also give a
      weak recommendation for the treatment of the majority of patients with AEx-IPF
      with corticosteroids. There is emerging evidence from clinical trials of
      investigational therapies that chronic treatment of IPF may reduce the incidence
      of AEx-IPF. Additional clinical trials investigating this are underway.

PMID- 23964927
TI  - Individual difference in serum oxytocin concentrations of calves and the
      correlation with those in dams.
AB  - We examined individual differences in serum oxytocin concentrations (OT) of
      calves, and assessed whether these differences were correlated with their dams'
      milk and serum OT. Eight Holstein (H), nine Japanese Shorthorn (JS), and six
      Japanese Black (JB) calves were examined. Blood was collected three times during
      the first month in H calves, while their dams' blood was collected three times
      prior to parturition. Milk was collected twice after parturition from H cows.
      Blood from JS and JB calves were collected at 1 and 4 months old, while of their
      dams only once before parturition. Serum OT in H calves at 7 days old was
      significantly correlated with that at 30 days. Serum OT of JS calves at 1 month
      old was significantly correlated to that at 4 months, while of JB calves was also
      positively correlated (r = 0.70). Serum OT of calves showed significant
      individual differences in each breed. Serum OT of calves was not correlated with
      the milk OT of dams, except for 3-day-old calves that fed on their dams' milk. We
      concluded that although serum OT differed among individuals, this difference was
      stable within each individual and not affected by the serum OT of the dams.

PMID- 23964928
TI  - Self-nanoemulsifying performance of two grades of Lauroglycol (Lauroglycol-90 and
      Lauroglycol-FCC) in the presence of mixed nonionic surfactants.
AB  - The present study was undertaken to evaluate the impact of various combinations
      of nonionic surfactants on self-nanoemulsifying performance of two grades of
      Lauroglycol (Lauroglycol-90 and Lauroglycol-FCC) in glibenclamide (GBN)
      nanoemulsion. Formulations (L1-L30) were prepared by spontaneous emulsification
      method. Prepared formulations were subjected to thermodynamic stability and self
      nanoemulsification test. Results of thermodynamic stability and self
      nanoemulsification tests were confirmed by further characterization of these
      formulations in terms of droplet size, viscosity, refractive index and %
      transmittance. Formulations prepared with Labrasol, HCO-60 and Gelucire-44/14
      were found to be suitable for self-emulsifying drug delivery system only whereas
      those prepared with Tween-80 and Cremophor-EL were found to be suitable for self
      nanoemulsifying or self-microemulsifying drug delivery system of GBN with respect
      to Lauroglycol-90 or Lauroglycol-FCC. Formulation L24 (Lauroglycol-FCC/Tween
      80/ethanol/water) was optimized as best formulation for self-nanoemulsifying drug
      delivery system of GBN. These results indicated that Tween-80 could be the best
      surfactant in terms of self-nanoemulsification.

PMID- 23964929
TI  - A soluble, low-temperature thermochromic and chemically reactive polydiacetylene.
AB  - The majority of polydiacetylenes (PDAs) described to date display thermochromic
      transitions above room temperature. By following a strategy that employs
      headgroups that do not participate in strong interactions, we have designed and
      prepared a liquid diacetylene (DA) monomer that solidifies at a temperature near
      0  degrees C. The isocyanate-containing DA monomer, DA-NCO, having this property
      does not undergo polymerization in its liquid state at room temperature. However,
      UV irradiation of frozen DA-NCO at 0  degrees C causes the instantaneous
      formation of a blue PDA (PDA-NCO). Interestingly, PDA-NCO was found to display a
      sharp blue-to-red color transition at a temperature near 11  degrees C. By taking
      advantage of its room temperature liquid-phase property, we were able to readily
      transfer the DA monomer to solid substrates by using common stamping and writing
      methods used for creating patterned PDA images. In addition, PDA-NCO dissolves in
      chloroform, giving a yellow solution that becomes red and simultaneously
      generates polymer aggregates when hexane is added. Finally, the isocyanate
      moieties present in PDA-NCO have been utilized to differentiate 1 degrees  from 2
      degrees  and 3 degrees  amines owing to the fact that a chloroform solution of
      PDA-NCO undergoes a rapid yellow-to-red color change associated with an insoluble
      urea-forming reaction with primary amines. 

PMID- 23964930
TI  - Living well with disability: needs, values and competing factors.
AB  - BACKGROUND: Obesity is more prevalent for disabled people (estimated as being
      between 27-62%) compared to the general population (17-22%). Disabled people are
      more likely to report poorer general health and acquire a range of obesity
      related secondary conditions. Although there are many physical activity and
      nutrition initiatives aimed at obesity prevention, little is known about whether
      these options are relevant and accessible for disabled people. The Living Well
      Study aimed to better understand the issues faced by disabled people when
      engaging in physical activity and healthy eating. METHODS: The study drew on a
      participatory action research design involving key stakeholders. There were two
      core cyclical phases (A and B), in which data collection was followed by a period
      of analysis, reflection and refinement. Focus groups and interviews were held
      with individuals who experience a range of disabilities, family members, service
      providers and representatives from disability advocacy groups. We sought to
      explore the importance and meaning of physical activity and healthy eating and
      factors that influenced engagement in these. Data in phase A were analysed using
      conventional content analysis drawing on constant comparative methods to identify
      themes of importance. In phase B, data analysis occurred alongside data
      collection, using a structured template to summarise participants' agreement or
      disagreement with the draft themes and recommendations, until the themes and
      recommendations were refined based on participants' corroboration. RESULTS: 146
      participants aged between 10-69 years, from both rural and urban areas and of
      different cultural backgrounds participated. Seven interconnecting themes that
      related to engagement in living well behaviours emerged with a wide range of
      external factors (such as people, knowledge, time, cost, identity and the
      environment) impacting on living well options. The central theme - It depends:
      needs, values and competing factors - emphasised the complexity faced by a
      disabled person when balancing the external factors with their own personal
      values and needs in order to arrive at a decision to engage in healthy living
      behaviours. CONCLUSIONS: Although disabled people experience similar issues when
      participating in healthy living behaviours as those living without disability,
      additional factors need to be addressed in order to improve opportunities for
      'living well' in these populations. This information has implications for health
      professionals to target the relevance and content of interventions.

PMID- 23964931
TI  - Taking our medicine--improving adherence in the accountability era.

PMID- 23964934
TI  - Pazopanib versus sunitinib in metastatic renal-cell carcinoma.
AB  - BACKGROUND: Pazopanib and sunitinib provided a progression-free survival benefit,
      as compared with placebo or interferon, in previous phase 3 studies involving
      patients with metastatic renal-cell carcinoma. This phase 3, randomized trial
      compared the efficacy and safety of pazopanib and sunitinib as first-line
      therapy. METHODS: We randomly assigned 1110 patients with clear-cell, metastatic
      renal-cell carcinoma, in a 1:1 ratio, to receive a continuous dose of pazopanib
      (800 mg once daily; 557 patients) or sunitinib in 6-week cycles (50 mg once daily
      for 4 weeks, followed by 2 weeks without treatment; 553 patients). The primary
      end point was progression-free survival as assessed by independent review, and
      the study was powered to show the noninferiority of pazopanib versus sunitinib.
      Secondary end points included overall survival, safety, and quality of life.
      RESULTS: Pazopanib was noninferior to sunitinib with respect to progression-free
      survival (hazard ratio for progression of disease or death from any cause, 1.05;
      95% confidence interval [CI], 0.90 to 1.22), meeting the predefined
      noninferiority margin (upper bound of the 95% confidence interval, <1.25).
      Overall survival was similar (hazard ratio for death with pazopanib, 0.91; 95%
      CI, 0.76 to 1.08). Patients treated with sunitinib, as compared with those
      treated with pazopanib, had a higher incidence of fatigue (63% vs. 55%), the hand
      foot syndrome (50% vs. 29%), and thrombocytopenia (78% vs. 41%); patients treated
      with pazopanib had a higher incidence of increased levels of alanine
      aminotransferase (60%, vs. 43% with sunitinib). The mean change from baseline in
      11 of 14 health-related quality-of-life domains, particularly those related to
      fatigue or soreness in the mouth, throat, hands, or feet, during the first 6
      months of treatment favored pazopanib (P<0.05 for all 11 comparisons).
      CONCLUSIONS: Pazopanib and sunitinib have similar efficacy, but the safety and
      quality-of-life profiles favor pazopanib. (Funded by GlaxoSmithKline
      Pharmaceuticals; COMPARZ ClinicalTrials.gov number, NCT00720941.).

PMID- 23964932
TI  - Vedolizumab as induction and maintenance therapy for ulcerative colitis.
AB  - BACKGROUND: Gut-selective blockade of lymphocyte trafficking by vedolizumab may
      constitute effective treatment for ulcerative colitis. METHODS: We conducted two
      integrated randomized, double-blind, placebo-controlled trials of vedolizumab in
      patients with active disease. In the trial of induction therapy, 374 patients
      (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at
      weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at
      weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance
      therapy, patients in either cohort who had a response to vedolizumab at week 6
      were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to
      switch to placebo for up to 52 weeks. A response was defined as a reduction in
      the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active
      disease) of at least 3 points and a decrease of at least 30% from baseline, with
      an accompanying decrease in the rectal bleeding subscore of at least 1 point or
      an absolute rectal bleeding subscore of 0 or 1. RESULTS: Response rates at week 6
      were 47.1% and 25.5% among patients in the vedolizumab group and placebo group,
      respectively (difference with adjustment for stratification factors, 21.7
      percentage points; 95% confidence interval [CI], 11.6 to 31.7; P<0.001). At week
      52, 41.8% of patients who continued to receive vedolizumab every 8 weeks and
      44.8% of patients who continued to receive vedolizumab every 4 weeks were in
      clinical remission (Mayo Clinic score <=2 and no subscore >1), as compared with
      15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage
      points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001]
      and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI,
      17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the
      vedolizumab and placebo groups. CONCLUSIONS: Vedolizumab was more effective than
      placebo as induction and maintenance therapy for ulcerative colitis. (Funded by
      Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.).

PMID- 23964935
TI  - Eastern equine encephalitis in Latin America.
AB  - BACKGROUND: The eastern equine encephalitis (EEE) and Venezuelan equine
      encephalitis (VEE) viruses are pathogens that infect humans and horses in the
      Americas. Outbreaks of neurologic disease in humans and horses were reported in
      Panama from May through early August 2010. METHODS: We performed antibody assays
      and tests to detect viral RNA and isolate the viruses in serum samples from
      hospitalized patients. Additional cases were identified with enhanced
      surveillance. RESULTS: A total of 19 patients were hospitalized for encephalitis.
      Among them, 7 had confirmed EEE, 3 had VEE, and 1 was infected with both viruses;
      3 patients died, 1 of whom had confirmed VEE. The clinical findings for patients
      with EEE included brain lesions, seizures that evolved to status epilepticus, and
      neurologic sequelae. An additional 99 suspected or probable cases of alphavirus
      infection were detected during active surveillance. In total, 13 cases were
      confirmed as EEE, along with 11 cases of VEE and 1 case of dual infection. A
      total of 50 cases in horses were confirmed as EEE and 8 as VEE; mixed etiologic
      factors were associated with 11 cases in horses. Phylogenetic analyses of
      isolates from 2 cases of equine infection with the EEE virus and 1 case of human
      infection with the VEE virus indicated that the viruses were of enzootic lineages
      previously identified in Panama rather than new introductions. CONCLUSIONS: Cases
      of EEE in humans in Latin America may be the result of ecologic changes that
      increased human contact with enzootic transmission cycles, genetic changes in EEE
      viral strains that resulted in increased human virulence, or an altered host
      range. (Funded by the National Institutes of Health and the Secretaria Nacional
      de Ciencia, Tecnologia e Innovacion, Panama.).

PMID- 23964936
TI  - Insecticidal bed nets and filariasis transmission in Papua New Guinea.
AB  - BACKGROUND: Global efforts to eliminate lymphatic filariasis are based on the
      annual mass administration of antifilarial drugs to reduce the microfilaria
      reservoir available to the mosquito vector. Insecticide-treated bed nets are
      being widely used in areas in which filariasis and malaria are coendemic.
      METHODS: We studied five villages in which five annual mass administrations of
      antifilarial drugs, which were completed in 1998, reduced the transmission of
      Wuchereria bancrofti, one of the nematodes that cause lymphatic filariasis. A
      total of 21,899 anopheles mosquitoes were collected for 26 months before and 11
      to 36 months after bed nets treated with long-lasting insecticide were
      distributed in 2009. We evaluated the status of filarial infection and the
      presence of W. bancrofti DNA in anopheline mosquitoes before and after the
      introduction of insecticide-treated bed nets. We then used a model of population
      dynamics to estimate the probabilities of transmission cessation. RESULTS:
      Village-specific rates of bites from anopheline mosquitoes ranged from 6.4 to
      61.3 bites per person per day before the bed-net distribution and from 1.1 to 9.4
      bites for 11 months after distribution (P<0.001). During the same period, the
      rate of detection of W. bancrofti in anopheline mosquitoes decreased from 1.8% to
      0.4% (P=0.005), and the rate of detection of filarial DNA decreased from 19.4% to
      14.9% (P=0.13). The annual transmission potential was 5 to 325 infective larvae
      inoculated per person per year before the bed-net distribution and 0 after the
      distribution. Among all five villages with a prevalence of microfilariae of 2 to
      38%, the probability of transmission cessation increased from less than 1.0%
      before the bed-net distribution to a range of 4.9 to 95% in the 11 months after
      distribution. CONCLUSIONS: Vector control with insecticide-treated bed nets is a
      valuable tool for W. bancrofti elimination in areas in which anopheline
      mosquitoes transmit the parasite. (Funded by the U.S. Public Health Service and
      the National Institutes of Health.).

PMID- 23964937
TI  - Tumor necrosis factor inhibitors for inflammatory bowel disease.

PMID- 23964938
TI  - Images in clinical medicine. African trypanosomiasis in Argentina.

PMID- 23964939
TI  - Case records of the Massachusetts General Hospital. Case 26-2013. A 46-year-old
      woman with muscle pain and swelling.

PMID- 23964940
TI  - Inhibition of leukocyte trafficking in inflammatory bowel disease.

PMID- 23964933
TI  - Vedolizumab as induction and maintenance therapy for Crohn's disease.
AB  - BACKGROUND: The efficacy of vedolizumab, an alpha4beta7 integrin antibody, in
      Crohn's disease is unknown. METHODS: In an integrated study with separate
      induction and maintenance trials, we assessed intravenous vedolizumab therapy
      (300 mg) in adults with active Crohn's disease. In the induction trial, 368
      patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and
      2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2
      (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461
      patients who had had a response to vedolizumab were randomly assigned to receive
      placebo or vedolizumab every 8 or 4 weeks until week 52. RESULTS: At week 6, a
      total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who
      received placebo were in clinical remission (i.e., had a score on the Crohn's
      Disease Activity Index [CDAI] of <=150, with scores ranging from 0 to
      approximately 600 and higher scores indicating greater disease activity)
      (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI
      100 response (>=100-point decrease in the CDAI score) (P=0.23). Among patients in
      cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those
      assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in
      clinical remission at week 52, as compared with 21.6% assigned to placebo
      (P<0.001 and P=0.004 for the two vedolizumab groups, respectively, vs. placebo).
      Antibodies against vedolizumab developed in 4.0% of the patients. Nasopharyngitis
      occurred more frequently, and headache and abdominal pain less frequently, in
      patients receiving vedolizumab than in patients receiving placebo. Vedolizumab,
      as compared with placebo, was associated with a higher rate of serious adverse
      events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections
      (5.5% vs. 3.0%). CONCLUSIONS: Vedolizumab-treated patients with active Crohn's
      disease were more likely than patients receiving placebo to have a remission, but
      not a CDAI-100 response, at week 6; patients with a response to induction therapy
      who continued to receive vedolizumab (rather than switching to placebo) were more
      likely to be in remission at week 52. Adverse events were more common with
      vedolizumab. (Funded by Millennium Pharmaceuticals; GEMINI 2 ClinicalTrials.gov
      number, NCT00783692.).

PMID- 23964941
TI  - Bulking up on beta cells.

PMID- 23964943
TI  - n-3 fatty acids in patients with cardiac risk factors.

PMID- 23964942
TI  - n-3 fatty acids in patients with cardiac risk factors.

PMID- 23964944
TI  - n-3 fatty acids in patients with cardiac risk factors.

PMID- 23964945
TI  - n-3 fatty acids in patients with cardiac risk factors.

PMID- 23964946
TI  - n-3 fatty acids in patients with cardiac risk factors.

PMID- 23964947
TI  - Respiratory syncytial virus and recurrent wheeze.

PMID- 23964948
TI  - Respiratory syncytial virus and recurrent wheeze.

PMID- 23964949
TI  - Enteropathogens and chronic illness in returning travelers.

PMID- 23964950
TI  - Enteropathogens and chronic illness in returning travelers.

PMID- 23964951
TI  - Enteropathogens and chronic illness in returning travelers.

PMID- 23964952
TI  - Infective endocarditis.

PMID- 23964953
TI  - Infective endocarditis.

PMID- 23964954
TI  - Increased height in HFE hemochromatosis.

PMID- 23964955
TI  - Images in clinical medicine. Familial primary cryofibrinogenemia.

PMID- 23964956
TI  - Racial/Ethnic Differences in Recent Drug Detoxification Enrollment and the Role
      of Discrimination and Neighborhood Factors.
AB  - Drug detoxification and long-term drug treatment utilization is lower for drug
      dependent minorities than Whites. Log-binomial regression was used to assess
      discrimination and neighborhood-level factors on past 6-month drug treatment
      utilization among 638 New York City (NYC) drug users between 2006 and 2009. Drug
      use discrimination was positively associated with detoxification and long-term
      treatment. Participants in higher concentrated Black neighborhoods were less
      likely to attend long-term treatment. Significantly fewer Blacks versus Whites
      and Hispanics reported drug-use discrimination, which may systematically filter
      drug users into treatment. More research is needed to understand social forms of
      discrimination and drug treatment.

PMID- 23964957
TI  - Using Classifiers to Identify Binge Drinkers Based on Drinking Motives.
AB  - A representative sample of 2,844 Dutch adult drinkers completed a questionnaire
      on drinking motives and drinking behavior in January 2011. Results were
      classified using regressions, decision trees, and support vector machines (SVMs).
      Using SVMs, the mean absolute error was minimal, whereas performance on
      identifying binge drinkers was high. Moreover, when comparing the structure of
      classifiers, there were differences in which drinking motives contribute to the
      performance of classifiers. Thus, classifiers are worthwhile to be used in
      research regarding (addictive) behaviors, because they contribute to explaining
      behavior and they can give different insights from more traditional data
      analytical approaches.

PMID- 23964958
TI  - Photoisomerization and photoinduced reactions in liquid CCl4 and CHCl3.
AB  - Transient absorption spectroscopy is used to follow the reactive intermediates
      involved in the first steps in the photochemistry initiated by ultraviolet (266
      nm wavelength) excitation of solutions of 1,5-hexadiene, isoprene, and 2,3
      dimethylbut-2-ene in carbon tetrachloride or chloroform. Ultraviolet and visible
      bands centered close to 330 and 500 nm in both solvents are assigned respectively
      to a charge transfer band of Cl-solvent complexes and the strong absorption band
      of a higher energy isomeric form of the solvent molecules (iso-CCl3-Cl or iso
      CHCl2-Cl). These assignments are supported by calculations of electronic
      excitation energies. The isomeric forms have significant contributions to their
      structures from charge-separated resonance forms and offer a reinterpretation of
      previous assignments of the carriers of the visible bands that were based on
      pulsed radiolysis experiments. Kinetic analysis demonstrates that the isomeric
      forms are produced via the Cl-solvent complexes. Addition of the unsaturated
      hydrocarbons provides a reactive loss channel for the Cl-solvent complexes, and
      reaction radii and bimolecular rate coefficients are derived from analysis using
      a Smoluchowski theory model. For reactions of Cl with 1,5-hexadiene, isoprene,
      and 2,3-dimethylbut-2-ene in CCl4, rate coefficients at 294 K are, respectively,
      (8.6 +/- 0.8) * 10(9), (9.5 +/- 1.6) * 10(9), and (1.7 +/- 0.1) * 10(10) M(-1) s(
      1). The larger reaction radius and rate coefficient for 2,3-dimethylbut-2-ene are
      interpreted as evidence for an H-atom abstraction channel that competes
      effectively with the channel involving addition of a Cl-atom to a C?C bond.
      However, the addition mechanism appears to dominate the reactions of 1,5
      hexadiene and isoprene. Two-photon excited CCl4 or CHCl3 can also ionize the
      diene or alkene solute. 

PMID- 23964959
TI  - Structural phase transitions in a new compound Eu2AgGe3.
AB  - A new intermetallic compound Eu2AgGe3 has been synthesized using high-frequency
      induction heating method. Single-crystal X-ray diffraction data showed that
      Eu2AgGe3 crystallizes in the orthorhombic Ba2LiSi3 structure type, with Fddd
      space group and lattice parameters a = 8.7069(17) A, b = 15.011(3) A, c =
      17.761(4) A. Eu2AgGe3 is composed of infinite arrays of hexagonal [Ag3Ge3] units
      stacked along the [001] direction, and the Eu sites are sandwiched between these
      parallel hexagonal networks. Temperature-dependent powder XRD data and DTA hint
      toward a structural phase transition from orthorhombic to hexagonal above 477 K
      and an unusual reversible transition to the original phase, i.e., orthorhombic
      phase at around 718 K. Magnetic measurements on Eu2AgGe3 sample show paramagnetic
      behavior above 100 K and weak ferromagnetic interactions below 80 K. Mossbauer
      spectroscopy and X-ray absorption near-edge spectroscopic (XANES) studies reveal
      that Eu atoms in Eu2AgGe3 exist in the divalent oxidation state. 

PMID- 23964960
TI  - Biodegradable mesostructured polymer membranes.
AB  - The extracellular matrix (ECM) has a quasi-ordered reticular mesostructure with
      feature sizes on the order of tenths of to a few hundred nanometers. Approaches
      to preparing biodegradable synthetic scaffolds for engineered tissues that have
      the critical mesostructure to mimic ECM are few. Here we present a simple and
      general solvent evaporation-induced self-assembly (EISA) approach to preparing
      concentrically reticular mesostructured polyol-polyester membranes. The
      mesostructures were formed by a novel self-assembly process without covalent or
      electrostatic interactions, which yielded feature sizes matching those of ECM.
      The mesostructured materials were nonionic, hydrophilic, and water-permeable and
      could be shaped into arbitrary geometries such as conformally molded tubular sacs
      and micropatterned meshes. Importantly, the mesostructured polymers were
      biodegradable and were used as ultrathin temporary substrates for engineering
      vascular tissue constructs. 

PMID- 23964961
TI  - Potent histone deacetylase inhibitors derived from 4-(aminomethyl)-N
      hydroxybenzamide with high selectivity for the HDAC6 isoform.
AB  - A screen for HDAC6 inhibitors identified acyl derivatives of 4-(aminomethyl)-N
      hydroxybenzamide as potent leads with unexpected selectivity over the other
      subtypes. We designed and synthesized constrained heterocyclic analogues such as
      tetrahydroisoquinolines that show further enhanced HDAC6 selectivity and
      inhibitory activity in cellular assays. Selectivity may be attributed to the
      benzylic spacer more effectively accessing the wider channel of HDAC6 compared to
      other HDAC subtypes as well as hydrophobic capping groups interacting with the
      protein surface near the rim of the active site. 

PMID- 23964962
TI  - Merozoite surface protein-3 alpha as a genetic marker for epidemiologic studies
      in Plasmodium vivax: a cautionary note.
AB  - BACKGROUND: Plasmodium vivax is the most widespread of the human malaria
      parasites in terms of geography, and is thought to present unique challenges to
      local efforts aimed at control and elimination. Parasite molecular markers can
      provide much needed data on P. vivax populations, but few such markers have been
      critically evaluated. One marker that has seen extensive use is the gene encoding
      merozoite surface protein 3-alpha (MSP-3alpha), a blood-stage antigen known to be
      highly variable among P. vivax isolates. Here, a sample of complete msp-3alpha
      gene sequences is analysed in order to assess its utility as a molecular marker
      for epidemiologic investigations. METHODS: Amplification, cloning and sequencing
      of additional P. vivax isolates from different geographic locations, including a
      set of Venezuelan field isolates (n = 10), yielded a sample of 48 complete msp
      3alpha coding sequences. Characterization of standard population genetic measures
      of diversity, phylogenetic analysis, and tests for recombination were performed.
      This allowed comparisons to patterns inferred from the in silico simulation of a
      polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP)
      protocol used widely. RESULTS: The larger sample of MSP-3alpha diversity revealed
      incongruence between the observed levels of nucleotide polymorphism, which were
      high in all populations, and the pattern of PCR-RFLP haplotype diversity. Indeed,
      PCR-RFLP haplotypes were not informative of a population's genetic diversity and
      identical haplotypes could be produced from analogous bands in the commonly used
      protocol. Evidence of frequent and variable insertion-deletion mutations and
      recurrent recombination between MSP-3alpha haplotypes complicated the inference
      of genetic diversity patterns and reduced the phylogenetic signal. CONCLUSIONS:
      The genetic diversity of P. vivax msp-3alpha involves intragenic recombination
      events. Whereas the high genetic diversity of msp-3alpha makes it a promising
      marker for some epidemiological applications, the ability of msp-3alpha PCR-RFLP
      analysis to accurately track parasites is limited. Local studies of the
      circulating alleles are needed before implementing PCR-RFLP approaches.
      Furthermore, evidence from the global sample analysed here suggests such msp
      3alpha PCR-RFLP methods are not suitable for broad geographic studies or tracking
      parasite populations for an extended period of time.

PMID- 23964963
TI  - Detection of dengue viruses using reverse transcription-loop-mediated isothermal
      amplification.
AB  - BACKGROUND: Early and rapid detection of dengue virus (DENV) infection during the
      febrile period is crucial for proper patient management and prevention of disease
      spread. An easy to perform and highly sensitive method is needed for routine
      implementation especially in the resource-limited rural healthcare settings where
      dengue is endemic. METHODS: A single-tube reverse transcription-loop-mediated
      isothermal amplification (RT-LAMP) assay with a set of nine primers was developed
      for the detection of all four DENV serotypes and their different genotypes. The
      sensitivity and specificity of the RT-LAMP were evaluated. The clinical
      applicability of RT-LAMP assay for detection of DENV RNA was assessed in a total
      of 305 sera of clinically-suspected dengue patients. The test results of RT-LAMP
      were statistically compared to those of quantitative reverse transcription
      polymerase chain reaction (qRT-PCR), IgM- and IgG-capture enzyme-linked
      immunosorbent assays (ELISA). RESULTS: Acute DENV infection was confirmed in 171
      samples (n = 305); 43.3% (74/171) and 46.8% (80/171) of the samples were positive
      for DENV using RT-LAMP and qRT-PCR, respectively. The combination of RT-LAMP with
      the dengue IgM and IgG ELISA increased detection of acute DENV infection to 97.7%
      (167/171), in comparison to only 70.8% (121/171) when dengue IgM and IgG ELISA
      alone were used. The RT-LAMP assays showed high concordance (kappa = 0.939) with
      the qRT-PCR. The RT-LAMP assay detected up to 10 copies of virus RNA within an
      hour but 100% reproducibility (12/12) was achieved with 100 copies. There was no
      cross reactivity of RT-LAMP with other closely related arboviruses. CONCLUSION:
      The RT-LAMP assay developed in this study is sensitive, specific and simple to
      perform. The assay improved the detection of dengue when used in combination with
      serological methods.

PMID- 23964965
TI  - [A novel typing method and scheme for Streptococcus pneumoniae].
AB  - STUDY AIM: To introduce a novel molecular PCR method for the typing of
      Streptococcus pneumonia in the National Reference Laboratory (NRL) for
      Streptococcal Infections. MATERIAL AND METHODS: Strains of Streptococcus
      pneumoniae are referred to the NRL from different regions of the Czech Republic.
      Generally, the identification and typing are based on strain morphology, optochin
      susceptibility, bile solubility, latex agglutination, and the Quellung reaction.
      Since 2012, a novel multiplex polymerase chain reaction (mPCR) assay has been
      introduced. The novel assay was tested on 210 S. pneumoniae isolates and 8
      isolates of the related species S. pseudopneumoniae, S. sanguinis, and S. oralis.
      RESULTS: The NRL for Streptococcal Infections has included a novel mPCR assay in
      the algorithm of S. pneumoniae identification and typing. The mPCR assay was able
      to identify and type any pneumococcal strain from the study collection, with the
      isolates of the related species remaining negative. The mPCR assay showed 100%
      sensitivity and specificity in this study. The pCR appeared to be an excellent
      tool for S. pneumoniae typing. CONCLUSION: Until recently, S. pneumoniae
      serotypes and serogroups were differentiated using a serological approach
      (Quellung reaction), but the NRL for Streptococcal Infections has switched to a
      novel mPCR assay. This molecular tool improves S. pneumoniae typing, making it
      more accurate.

PMID- 23964964
TI  - [Antibiotic resistance in nontyphoidal salmonellae serovars in the Czech
      Republic].
AB  - STUDY AIM: To determine antibiotic resistance and incidence of multidrug
      resistance among Nontyphoidal salmonellae serovars isolated from humans. MATERIAL
      AND METHODS: Consecutive Salmonella isolates from patients, recovered in 48
      microbiology laboratories in May 2012, were analyzed in the respective reference
      laboratories at the National Institute of Public Health. Strains were re
      identified and differentiated into serovars. Their minimum inhibitory
      concentrations (MICs) to 11 antibiotics were determined by the microdilution
      method. RESULTS: Of 25 serovars identified among 637 strains of Salmonella
      enterica, the most frequent were Enteritidis (87.0 %), Typhimurium (4.9 %), and
      monophasic Typhimurium 4,[5],12:i:- (2.0 %) and Mbandaka (0.6 %); other serovars
      were rare. Altogether 558 strains (87.6 %) were susceptible to all antibiotics
      tested and the remaining 79 strains were resistant to one or more antibiotics.
      The prevalence rates of resistance to individual antibiotics among 637 study
      strains were as follows: ampicillin 8.5%, tetracycline 5.7%, sulfamethoxazole
      5.2%, cipro-floxacin 3.8%, and chloramphenicol 2.5%. Resistance to gentamicin,
      trimethoprim, and third and fourth generation cephalosporins was rare ( 0.5%) and
      none of the study strains showed resistance to meropenem. Three producers of
      extended spectrum beta-lactamase were multidrug resistant and two of them
      recovered from twins exhibited a different pattern of resistance. Resistant
      strains were most often assigned to the following serovars: Enteritidis (49.4%),
      Typhimurium (26.6%), and monophasic Typhimurium (15.2%). While only 7% (39 of 554
      strains) of Enteritidis strains were resistant, the serovars Typhimurium and its
      monophasic variant 4,[5],12:i:- showed high rates of resistance, i.e. 66.7 and
      92.3%, respectively. Furthermore, resistance was revealed in all strains of the
      serovars Virchow (n = 3), Kentucky (n = 1), and Newport (n = 1), in two of three
      strains of the serovar Infantis, and in one of two strains of the serovar
      Stanley. All five blood isolates were assigned to the serovar Enteritidis and one
      of them showed resistance to ciprofloxacin. Of 79 resistant strains, 26.6% showed
      resistance to ampicillin only and 24.1% to ciprofloxacin only, with multidrug
      resistance, i.e. resistance to three or more antibiotics, confirmed in 43.0% of
      strains. CONCLUSION: Despite a relatively low prevalence of resistance to the
      antibiotics tested among 637 study strains, the following alarming findings were
      made: Detection of Salmonella enterica strains resistant to ciprofloxacin as the
      drug of choice or to higher generation cephalosporins and multidrug resistance
      revealed in two thirds of the strains of the serovar Typhimurium and in all but
      one strains of its monophasic variant 4,[5],12:i:-.

PMID- 23964966
TI  - [Salmonellosis outbreaks in the Czech Republic in 2012].
AB  - In 2012, the Brno laboratory of the National Institute of Public Health
      investigated 143 human and 10 food-borne Salmonella strains. All strains were
      linked to salmonellosis outbreaks in various areas or represented rare serotypes
      that had emerged more often in some periods. These strains were matched to 22
      outbreaks reported in the Czech Republic. Phenotyping and genotyping revealed
      that the cause of most outbreaks (82%) was the serotype Enteritidis, but other
      serotypes that are rare in the Czech Republic (S. Mikawasima, S. 9,12:l,v:-, S.
      Indiana, or S. Stanley) were also involved in some outbreaks.

PMID- 23964967
TI  - [Intravenous and subcutaneous immunoglobulin therapy].
AB  - Patients with agammaglobulinaemia and hypogammaglobulinaemia require
      immunoglobulin G (IgG) replacement therapy to prevent serious infections. Since
      the 1950s, therapy with human immune globulin products has been the standard of
      treatment. Currently, the most common routes of administration of IgG replacement
      therapy are intravenous (IVIG) or subcutaneous (SCIG). The home therapy may
      improve the quality of life in patients who require lifelong IgG replacement. The
      -anti-IgA antibody test identifies the patients with the risk of anaphylactoid
      reactions in IVIG replacement. The SCIG delivery may be used in patients with
      anti-IgA antibodies and previous systemic reactions to IVIG.

PMID- 23964969
TI  - [Fifty years of the Institute of Epidemiology, Faculty of Medicine, Comenius
      University, Bratislava].

PMID- 23964968
TI  - [Prevalence estimates of problem drug users in the Czech Republic in 2006 and
      2007 using the capture-recapture method].
AB  - BACKGROUND: An estimate of problem drug use prevalence is a substantial part of
      the monitoring of the epidemiological situation in drug use and its consequences
      and an important indicator for drug policy implementation. The capture-recapture
      method (CRM) is one of the most commonly used standard methods for this purpose
      worldwide. METHODS AND MATERIAL: The CRM was used to estimate the numbers of
      problem drug users (PDU) and problem users of opiates/opioids (PUO) in the Czech
      Republic in 2006 and 2007. The following data sources were used: the General
      Health Insurance Company records of payments to out- and in-patient psychiatric
      care providers, records of admissions to psychiatric hospitals, replacement
      therapy register, and reports of newly diagnosed cases of viral hepatitis. Cases
      were defined as diagnoses F11, F15, and F19 according to the International
      Classification of Diseases, Tenth Revision (ICD-10) from the health insurance and
      admission records, the replacement therapy register covers PUO by definition, and
      injecting drug users were selected from reported cases of viral hepatitis. Log
      linear analysis in Rcapture (R) was performed and the Akaike information
      criterion was used for model selection. RESULTS: Altogether 12,882 and 13,505
      individuals entered into analysis of PDUs and 5146 and 5409 individuals entered
      into analysis of PUO in 2006 and 2007, respectively. The estimates of PDUs were
      23,900 (95% CI: 20,700-28,500) in 2006 and 31,000 (25,500-39,400) in 2007. The
      estimates of PUO were 6,864 (6,641-7,113) in 2006 and 7,096 (6,871-7,346) in
      2007. The male/female ratio was 2.2/1. In PDU estimates, 83% were in the age
      range 15-34 and 17% were aged above 34; in PUO estimates, the respective rates
      were 80% and 20%. The prevalence rates of PDU in the age range 15-64 were 2.28
      and 2.95 per 1,000 population in 2006 and 2007, respectively. The prevalence
      rates of PUO in the age range 15-64 were 0.65 and 0.67 per 1,000 in 2006 and
      2007, respectively. The highest prevalence of both PDUs and PUO was observed in
      the Usti Region and Prague, followed by the Karlovy Vary, Plzen, and Central
      Bohemia Regions. CONCLUSION: PDU estimates in the Czech Republic obtained using
      the CRM are consistent with those derived by other methods. The major drawbacks
      are the quality of potential data sources and hassles in their acquisition and
      preparation. The interconnection of the available data sources also limits the
      validity and representativeness of estimates and therefore, another independent
      data source(s) should be sought in the future.

PMID- 23964970
TI  - The arbuscular mycorrhizal fungus, Glomus irregulare, controls the mycotoxin
      production of Fusarium sambucinum in the pathogenesis of potato.
AB  - Trichothecenes are an important family of mycotoxins produced by several species
      of the genus Fusarium. These fungi cause serious disease on infected plants and
      postharvest storage of crops, and the toxins can cause health problems for humans
      and animals. Unfortunately, there are few methods for controlling mycotoxin
      production by fungal pathogens, and most rely on chemicals, creating therefore
      subsequent problems of chemical resistance. We tested the impact of the symbiotic
      arbuscular mycorrhizal fungus Glomus irregulare on a trichothecene-producing
      strain of Fusarium sambucinum isolated from naturally infected potato plants.
      Using dual in vitro cultures, we showed that G. irregulare inhibited the growth
      of F. sambucinum and significantly reduced the production of the trichothecene 4,
      15-diacetoxyscirpenol (DAS). Furthermore, using G. irregulare-colonized potato
      plants infected with F. sambucinum, we found that the G. irregulare treatment
      inhibited the production of DAS in roots and tubers. Thus, in addition to the
      known beneficial effect of mycorrhizal symbiosis on plant growth, we found that
      G. irregulare controlled the growth of a virulent fungal pathogen and reduced
      production of a mycotoxin. This previously undescribed, biological control of
      Fusarium mycotoxin production by G. irregulare has potential implications for
      improved potato crop production and food safety. 

PMID- 23964971
TI  - Lateralization of categorical and coordinate spatial functions: a study of
      unilateral stroke patients.
AB  - Abstract Sixty patients with unilateral stroke (half with left hemisphere damage
      and half with right hemisphere damage) and a control group (N = 15) matched for
      age and educational level were tested in two experiments. In one experiment they
      were first shown, on each trial, a sample drawing depicting one or more objects.
      Following a short delay, they were asked to identify the drawing when it was
      paired with a drawing in which the same object(s) was transformed in categorical
      or coordinate spatial relations. In the other experiment, the same subjects first
      were shown, on each trial, a sample drawing. They then judged which of two
      variants (each in one type of spatial relation) looked more similar to the sample
      drawing. Typically, patients with left-sided stroke mistakenly identified the
      categorical transformation for the sample drawing in the first task; in the
      second task, they judged the categorical transformation as more similar to the
      sample drawing. Patients with right-sided stroke mistakenly identified the
      coordinate transformations for the sample drawing in the first task, and, in the
      second task, typically judged the drawings transformed along coordinate spatial
      relations as more similar to the sample drawing. These findings provide evidence
      for complementary lateralization of the two types of spatial perception. It can
      therefore be inferred that separate functional subsystems process the two types
      of spatial relations. 

PMID- 23964972
TI  - Neurophysiological Manifestations of Phonological Processing: Latency Variation
      of a Negative ERP Component Timelocked to Phonological Mismatch.
AB  - Abstract Two experiments examined phonological priming effects on reaction times,
      error rates, and event-related brain potential (ERP) measures in an auditory
      lexical decision task. In Experiment 1 related prime-target pairs rhymed, and in
      Experiment 2 they alliterated (i.e., shared the consonantal onset and vowel).
      Event-related potentials were recorded in a delayed response task. Reaction times
      and error rates were obtained both for the delayed and an immediate response
      task. The behavioral data of Experiment 1 provided evidence for phonological
      facilitation of word, but not of nonword decisions. The brain potentials were
      more negative to unrelated than to rhyming word-word pairs between 450 and 700
      rnsec after target onset. This negative enhancement was not present for word
      nonword pairs. Thus, the ERP results match the behavioral data. The behavioral
      data of Experiment 2 provided no evidence for phonological Facilitation. However,
      between 250 and 450 msec after target onset, i.e., considerably earlier than in
      Experiment 1, brain potentials were more negative for unrelated than for
      alliterating Word-word and word-nonword pairs. It is argued that the ERP effects
      in the two experiments could be modulations of the same underlying component,
      possibly the N400. The difference in the timing of the effects is likely to be
      due to the fact that the shared segments in related stimulus pairs appeared in
      different word positions in the two experiments. 

PMID- 23964973
TI  - Parietal damage and narrow "spotlight" spatial attention.
AB  - Abstract Patients with parietal volume loss showed electrophysiological and
      behavioral signs of abnormally narrow regions of enhancement of sensory
      stimulation at an attended location. On a test of focused spatial attention, when
      compared to normal control subjects and patients without parietal abnormality,
      patients with abnormalities of parietal cortex demonstrated (1) faster button
      press RTs to targets, (2) earlier P3b event-related potential (ERP) latencies to
      targets, and (3) larger than normal P1 ERP attention effects (i.e., greater than
      normal enhancement of sensory responses at an attended location). These data are
      evidence for visual attention distributed as a spotlight at the attentional focus
      with little surrounding processing enhancement. This dysfunctional attentional
      map facilitates simple responses within the attentional beam quite well, but
      could hinder responses outside the beam. Severely gated sensory responses outside
      the immediate attentional focus are likely to result in severely delayed
      responses to information in those locations. This would be consistent with the
      response delays seen in patients with parietal damage following an incorrect
      spatial cue (extinction-like pattern), and also with clinical observations of
      inattention in such patients. The patterns of sensory enhancement seen in these
      data suggest a mechanism that may underlie the impairments in spatial attention
      that follow damage to parietal cortex, and help to specify the role of parietal
      cortex in spatial attention. 

PMID- 23964974
TI  - Language-Related ERPs: Scalp Distributions and Modulation by Word Type and
      Semantic Priming.
AB  - Abstract Event-related potentials (ERPs) were recorded from the scalp to
      investigate the processing of word stimuli. Three tasks were used: (1) a task
      comparing words that provided an anomalous or normal sentence ending, (2) a word
      list task in which different word types were examined, and (3) a word-list task
      in which semantic priming was examined. ERPs were recorded from a 50-channel
      montage in an attempt to dissociate overlapping ERP features by their scalp
      distributions. The focus of these studies was the N400, an ERP previously
      associated with language processing (Kutas & Hillyard, 1980). The temporal
      interval typically associated with N400 (250-500 msec) was found to contain
      overlapping ERP features. Two of these features were common to both sentence and
      word-list tasks-but one appeared different. Anomalous sentence endings and words
      with semantic content in lists both showed coincident negative left
      frontotemporal and midline-anterior ERP foci, peaking at 332 msec for sentences
      and 316 msec for word lists. The most negative voltage obtained in the sentence
      task peaked at 386 msec and had a midline-posterior focus. A right frontotemporal
      focus developed after the midline-posterior focus and outlasted its duration. The
      most negative voltage for content words in lists was reached at 364 msec. The
      distribution of this ERP was extensive over the midline and appeared to differ
      from that observed in the sentence task. Modulation of language-related ERPs by
      word type and semantic priming was investigated using the word-list tasks, which
      required category-detection responses. Two novel findings were obtained: (1) The
      ERP distributions for words serving grammatical function and content words
      differed substantially in word lists. Even when devoid of any sentence context,
      function words presented significantly attenuated measures of N400 compared to
      content words. These findings support hypotheses that suggest a differential
      processing of content and function words. (2) Semantic priming functionally
      dissociated two ERP features in the 250-500 msec range. The later and most
      negative midline ERP feature (peaking at 364 msec) was attenuated by semantic
      priming. However, the earlier left frontotemporal feature (peaking at 316 msec)
      was enhanced by semantic priming. The isolation of this novel language-related
      ERF' that is sensitive to semantic manipulations has important consequences for
      temporal and mechanistic aspects of theories of language processing. 

PMID- 23964975
TI  - Event-related potential components reflect phonological and semantic processing
      of the terminal word of spoken sentences.
AB  - Abstract An event-related brain potential (ERP) reflecting the acoustic-phonetic
      process in the phonological stage of word processing was recorded to the terminal
      words of spoken sentences. The peak latency of this negative-going response
      occurred between 270 and 300 msec after the onset of the terminal word. The
      independence of this response (the phonological mismatch negativity, PMN) from
      the ERP component known to be sensitive to semantic violations (N400) was
      demonstrated by manipulating sentence endings so that phonemic and semantic
      violations occurred together or separately. Four conditions used sentences that
      ended with (1) the highest Cloze probability word (e.g., "The piano was out of
      tune."), (2) a word having the same initial phoneme of the highest Cloze
      probability word but that was, in fact, semantically anomalous (e.g., "The
      gambler had a streak of bad luggage."), (3) a word having an initial phoneme
      different from that of the highest Cloze probability word but that was, in fact,
      semantically appropriate (e.g., "Don caught the ball with his glove."), or (4) a
      word that was semantically anomalous and, therefore, had an initial phoneme that
      was totally unexpected given the sentence's context (e.g., "The dog chased our
      cat up the queen"). Neither the PMN nor the N400 was found in the first
      condition. Only an N400 was observed in the second condition while only a PMN was
      seen in the third. Both responses were elicited in the last condition. Finally, a
      delayed N400 occurred to semantic violations in the second condition where the
      initial phoneme was identical to that of the highest Cloze probability ending.
      Results are discussed with regard to the Cohort model of word recognition. 

PMID- 23964976
TI  - Monitoring the visual world: hemispheric asymmetries and subcortical processes in
      attention.
AB  - Abstract Hemispheric specialization and subcortical processes in visual anention
      were investigated in callosotomy (split-brain) patients by measuring reaction
      times to lateralized stimuli in a spatial cuing paradigm. Cuing effects were
      obtained for targets presented to the right hemisphere (left visual hemifield)
      but not for those presented to the left hemisphere. These cuing effects were
      manifest as faster reaction times when the cue correctly indicated the location
      of the subsequent target (valid trials), as compared to trials in which the cue
      and target appeared in opposite hemifields (invalid trials). This pattern
      suggests that the right hemisphere allocated attention to cued locations in
      either visual hemifield, whereas the left hemisphere allocated attention
      predominantly to the right hemifield. This finding is consistent with a body of
      evidence from studies in patients with cortical lesions who display different
      attentional deficits for right versus left hemisphere damage. Because the present
      pattern occurs in patients whose cerebral hemispheres are separated at the
      cortical level, it suggests that right hemisphere attentional allocation to
      events in the ipsilateral visual half-field is mediated in part via intact
      subcortical systems. 

PMID- 23964977
TI  - Cognitive bias, functional cortical geometry, and the frontal lobes: laterality,
      sex, and handedness.
AB  - Abstract Performance of patients with quadrant lesions on the inherently
      ambiguous Cognitive Bias Task (CBT) suggests sexual dimorphism in the fundamental
      aspects of functional cortical geometry, by emphasizing different cerebral axes.
      In right-handed males, extreme context-dependent and context-independent response
      selection biases are reciprocally linked to left vs. right frontal systems. In
      right-handed females, these complementary biases appear to be reciprocally linked
      to posterior vs. frontal cortices. Frontal lobe functions are more lateralized in
      males than females due to sexual dimorphism of the left frontal systems. Both in
      males and females, patterns of CBT scores in non-right-handers with quadrant
      lesions are opposite to those found in right-handers. This suggests the existence
      of two functionally and neurally distinct cognitive selection mechanisms. Both
      mechanisms involve the frontal lobes, but their exact neuroanatomy depends on sex
      and handedness. 

PMID- 23964978
TI  - On cognitive neuroscience.
AB  - Abstract Stephen M. Kosslyn is Professor of Psychology at Harvard University and
      an Associate Psychologist in the Department of Neurology at the Massachusetts
      General Hospital. He received his B.A. in 1970 from UCLA and his Ph.D. from
      Stanford University in 1974, both in psychology, and taught at Johns Hopkins,
      Harvard, and Brandeis Universities before joining the Harvard Faculty as
      Professor of Psychology in 1983. His work focuses on the nature of visual mental
      imagery and high-level vision, as well as applications of psychological
      principles to visual display design. He has published over 125 papers on these
      topics, co-edited five books, and authored or co-authored five books. His books
      include Image and Mind (1980), Ghosts in the Mind's Machine (1983), Wet Mind: The
      New Cognitive Neuroscience (with 0. Koenig, 1992), Elements of Graph Design
      (1994), and Image and Brain: The Resolution of the Imagery Debate (1994). Dr.
      Kosslyn has received numerous honors, including the National Academy of Sciences
      Initiatives in Research Award, is currently on the editorial boards of many
      professional journals, and has served on several National Research Council
      committees to advise the government on new technologies. 

PMID- 23964979
TI  - Tensor hypercontraction equation-of-motion second-order approximate coupled
      cluster: electronic excitation energies in O(N4) time.
AB  - The tensor hypercontraction (THC) formalism is applied to equation-of-motion
      second-order approximate coupled cluster singles and doubles (EOM-CC2). The
      resulting method, THC-EOM-CC2, is shown to scale as O(N4), a reduction of one
      order from the formal O(N5) scaling of conventional EOM-CC2. Numerical tests for
      a variety of molecules show that errors of less than 0.02 eV are introduced into
      the excitation energies.

PMID- 23964981
TI  - Characterization of the properties of seven promoters in the motor cortex of rats
      and monkeys after lentiviral vector-mediated gene transfer.
AB  - Lentiviral vectors deliver transgenes efficiently to a wide range of neuronal
      cell types in the mammalian central nervous system. To drive gene expression,
      internal promoters are essential; however, the in vivo properties of promoters,
      such as their cell type specificity and gene expression activity, are not well
      known, especially in the nonhuman primate brain. Here, the properties of five
      ubiquitous promoters (murine stem cell virus [MSCV], cytomegalovirus [CMV], CMV
      early enhancer/chicken beta-actin [CAG], human elongation factor-1alpha [EF
      1alpha], and Rous sarcoma virus [RSV]) and two cell type-specific promoters (rat
      synapsin I and mouse alpha-calcium/calmodulin-dependent protein kinase II
      [CaMKIIalpha]) in rat and monkey motor cortices in vivo were characterized.
      Vesicular stomatitis virus G (VSV-G)-pseudotyped lentiviral vectors expressing
      enhanced green fluorescent protein (EGFP) under the control of the various
      promoters were prepared and injected into rat and monkey motor cortices.
      Immunohistochemical analysis revealed that all of the VSV-G-pseudotyped
      lentiviral vectors had strong endogenous neuronal tropisms in rat and monkey
      brains. Among the seven promoters, the CMV promoter showed modest expression in
      glial cells (9.4%) of the rat brain, whereas the five ubiquitous promoters (MSCV,
      CMV, CAG, EF-1alpha, and RSV) showed expression in glial cells (7.0-14.7%) in the
      monkey brain. Cell type-specific synapsin I and CaMKIIalpha promoters showed
      excitatory neuron-specific expression in the monkey brain (synapsin I, 99.7%;
      CaMKIIalpha, 100.0%), but their specificities for excitatory neurons were
      significantly lower in the rat brain (synapsin I, 94.6%; CaMKIIalpha, 93.7%).
      These findings could be useful in basic and clinical neuroscience research for
      the design of vectors that efficiently deliver and express transgenes into rat
      and monkey brains.

PMID- 23964982
TI  - Interconnections of reactive oxygen species homeostasis and circadian rhythm in
      Neurospora crassa.
AB  - SIGNIFICANCE: Both circadian rhythm and the production of reactive oxygen species
      (ROS) are fundamental features of aerobic eukaryotic cells. The circadian clock
      enhances the fitness of organisms by enabling them to anticipate cycling changes
      in the surroundings. ROS generation in the cell is often altered in response to
      environmental changes, but oscillations in ROS levels may also reflect endogenous
      metabolic fluctuations governed by the circadian clock. On the other hand, an
      effective regulation and timing of antioxidant mechanisms may be crucial in the
      defense of cellular integrity. Thus, an interaction between the circadian
      timekeeping machinery and ROS homeostasis or signaling in both directions may be
      of advantage at all phylogenetic levels. RECENT ADVANCES: The Frequency-White
      Collar-1 and White Collar-2 oscillator (FWO) of the filamentous fungus Neurospora
      crassa is well characterized at the molecular level. Several members of the ROS
      homeostasis were found to be controlled by the circadian clock, and ROS levels
      display circadian rhythm in Neurospora. On the other hand, multiple data indicate
      that ROS affect the molecular oscillator. CRITICAL ISSUES: Increasing evidence
      suggests the interplay between ROS homeostasis and oscillators that may be
      partially or fully independent of the FWO. In addition, ROS may be part of a
      complex cellular network synchronizing non-transcriptional oscillators with
      timekeeping machineries based on the classical transcription-translation feedback
      mechanism. FUTURE DIRECTIONS: Further investigations are needed to clarify how
      the different layers of the bidirectional interactions between ROS homeostasis
      and circadian regulation are interconnected.

PMID- 23964983
TI  - A concise total synthesis of (+)-scholarisine A empowered by a unique C-H
      arylation.
AB  - The structurally unique akuammiline alkaloid (+)-scholarisine A was synthesized
      in 14 steps from a known enone (15 steps from commercial materials) through a
      route empowered by a unique C-H arylation reaction to forge its polycyclic core.
      Additional key steps include a pyrone Diels-Alder reaction and a radical
      cyclization/Keck allylation to fashion the core cage polycycle and one of the
      molecule's quaternary centers, as well as the use of a carefully positioned
      pendant hydroxyl group to facilitate the chemoselective reduction of an extremely
      unreactive lactam in the presence of a readily reduced lactone. 

PMID- 23964984
TI  - Computed tomography-assessed right ventricular dysfunction and risk
      stratification of patients with acute non-massive pulmonary embolism: systematic
      review and meta-analysis.
AB  - BACKGROUND: The ability of computed tomography (CT)-assessed right ventricular
      dysfunction (RVD) to identify normotensive patients with acute pulmonary embolism
      (PE) at high risk of mortality or adverse outcome lacks clarity. METHODS AND
      RESULTS: We performed a systematic review and a meta-analysis of studies in
      normotensive patients with acute PE to assess the prognostic value of CT-assessed
      RVD for death and a predefined composite outcome of PE-related complications. We
      conducted unrestricted searches of MEDLINE and EMBASE from 1980 to March 2013,
      and used the terms 'computed tomography', 'pulmonary embolism', and 'prognos*'.
      We used a random-effects model to pool study results, funnel-plot inspection to
      evaluate for publication bias, and I(2) testing to assess for heterogeneity. The
      analysis included data from 10 studies (2288 patients). Overall, 99 of 1268
      patients with RVD assessed by CT died (7.8%; 95% confidence interval [CI] 6.3
      9.3) as compared with 52 of 1020 without RVD (5.1%; 95% CI 3.7-6.4). CT-assessed
      RVD had significant associations with mortality (odds ratio [OR] 1.8; 95% CI 1.3
      2.6), with death resulting from PE (OR 7.4; 95% CI 1.4-39.5), and with PE-related
      complications (OR 2.4; 95% CI 1.2-4.7). Pooled likelihood ratios (LRs) were not
      extreme (negative LR 0.71; 95% CI 0.57-0.89; and positive LR 1.27; 95% CI 1.12
      1.43). CONCLUSIONS: Although RVD assessed by CT showed an association with an
      increased risk of mortality in patients with hemodynamically stable PE, it
      resulted in only small increases in the ability to classify risk.

PMID- 23964985
TI  - The General Relationship Between Universal Human Values and Adolescents'
      Problem/Pathological Gambling in Macao: A Parsimonious, Quantitative Model.
AB  - This study modeled the general relationship between individual Macao adolescents'
      universal human values, measured by the Schwartz Values Inventory, and their
      problem/pathological gambling, indicated by the South Oaks Gambling Screen, using
      parsimonious, quantitative structural equation modeling. Data were collected
      through 471 questionnaires (261 females and 210 males) in 2010. Of the 10 value
      types in the Schwartz Values Inventory and derived value subtypes, only the human
      value subtype "nonfaith tradition" was found to be (negatively) related to
      problem/pathological gambling in the model. The corresponding factor loading was 
      0.07 (p = .015). This study was supported by the Education and Youth Affairs
      Bureau, the Government of Macao.

PMID- 23964986
TI  - Let's Get This Party Started: The Effects of Descriptive and Injunctive Norms on
      Preparty Behavior in College Students.
AB  - Participants (N = 202) were students at a college in the northeastern United
      States who participated in the 2010 Core Alcohol and Drug survey. Data were
      collected on prepartying behavior, preparty social norms, and individual
      difference variables. Using multivariate logistic and least-squares regression,
      it was found that descriptive social norms were associated with prepartying in
      women and injunctive social norms were associated with prepartying in men.
      Prepartying also was found to be negatively related to underage status and GPA in
      women and positively related to Greek membership and athlete status in men.
      Implications for social-norms interventions and suggestions for future social
      norms research are discussed.

PMID- 23964987
TI  - "He Was the Story of My Drug Use Life": A Longitudinal Qualitative Study of the
      Impact of Partner Incarceration on Substance Misuse Patterns Among African
      American Women.
AB  - This NIH-funded longitudinal qualitative study explored pathways through which
      partner incarceration affected substance misuse among African American women.
      Four waves of semi-structured interviews were conducted with 17 substance
      misusing African American women whose partners had recently been incarcerated.
      Data were collected in Atlanta, Georgia, during 2010-2011. Transcripts were
      analyzed using grounded theory methods. Analyses suggest that partner
      incarceration initially precipitated multiple crises in women's lives (e.g.,
      homelessness); over time, and with formal and informal support, women got their
      lives "back on track." Substance misuse declined over time, though spiked for
      some women during the crisis period. We discuss implications for research and
      interventions.

PMID- 23964988
TI  - Personality Risk Factors and Readiness to Change in Mandated and Voluntary
      College Students Enrolled in an Alcohol Intervention Program.
AB  - This study compared personality risk factors and readiness to change drinking
      behavior among mandated and volunteer college students. The sample (N = 583)
      completed three measures of motivation to change and personality risk factors at
      baseline, 3 months, and 6 months between 2011 and 2012. Linear mixed models were
      used to determine an association of continuous outcome variable(s) with
      covariates over time. Participants in the action stage had lower impulsivity
      scores. Gender was significant, with females showing the highest anxiety and
      lowest sensation seeking. The findings indicate a number of future directions to
      advance innovative alcohol intervention and treatment programs on college
      campuses.

PMID- 23964989
TI  - A tale of tails: alkyl chain directed formation of 2D porous networks reveals odd
      even effects and unexpected bicomponent phase behavior.
AB  - Supramolecular self-assembly of suitably functionalized building blocks on
      surfaces can serve as an excellent test-bed to gain understanding and control
      over multicomponent self-assembly in more complex matter. Here we employ a
      powerful combination of scanning tunnelling microscopy (STM) and molecular
      modeling to uncover two-dimensional (2D) crystallization and mixing behavior of a
      series of alkylated building blocks based on dehydrobenzo[12]annulene, forming
      arrays of nanowells. Thorough STM investigation employing high-resolution spatial
      imaging, use of specially designed marker molecules, statistical analysis and
      thermal stability measurements revealed rich and complex supramolecular
      chemistry, highlighting the impact of odd-even effects on the phase behavior. The
      methodology and analysis presented in this work can be easily adapted to the self
      assembly of other alkylated building blocks. 

PMID- 23964990
TI  - New method to predict the surface tension of complex synthetic and biological
      polyelectrolyte/surfactant mixtures.
AB  - Although the surface tension of complex mixtures determines the fate of many
      important natural processes, the property is notoriously difficult to interpret.
      Here we announce a new method that successfully predicts the surface tension of
      two synthetic and one biological polyelectrolyte/surfactant mixtures in the phase
      separation region after dynamic changes in the bulk phase behavior have reached
      completion. The approach is based on the nonequilibrium framework of a lack of
      colloidal stability of bulk complexes in compositions around the charge match
      point of the oppositely charged components and requires as input parameters only
      the surface tension isotherm of the pure surfactant and some bulk measurements of
      the mixtures; no surface measurements of the mixtures are required. The
      complexity of the problem is reduced to a single empirical equation. This
      simplification in our understanding of the surface properties of strongly
      interacting mixtures involving macromolecules can lead to the optimization of
      applications involving synthetic polymers and biomacromolecules such as DNA at
      surfaces. 

PMID- 23964991
TI  - Anti-inflammatory effects of extracellular cyclosporins are exclusively mediated
      by CD147.
AB  - Leukocyte trafficking and recruitment is a critical process in host immune
      surveillance and in inflammatory diseases. Extracellular cyclophilins (eCyps)
      have been identified as a novel class of chemotactic mediators. The impact of
      eCyp/CD147 interactions for the recruitment of leukocytes during inflammation was
      analyzed using a structurally simplified cell-impermeable eCyp inhibitor. This
      compound was highly effective at inhibiting leukocyte migration toward CypA in
      vitro as well as in the recruitment of leukocytes during inflammation in a mouse
      model of experimentally induced peritonitis and delayed-type hypersensitivity
      reaction. By using CD147-/- mice in combination with the cell-impermeable eCyp
      inhibitor, we were able to show that the action of eCyps in inflammation is
      exclusively mediated by interaction with CD147. Our findings suggest that
      blocking eCyps may be an effective therapeutic target for reducing inflammatory
      diseases associated with leukocyte recruitment. 

PMID- 23964992
TI  - The influence of crate height on selected biochemical indices in captive-reared
      mallards.
AB  - The aim of this study was to investigate the effects of crate type (particularly
      its height) on selected biochemical indices in captive-reared mallards (Anas
      platyrhynchos). The physiological changes in response to 2-h crating in crates of
      either 20 cm or 26 cm height were monitored in 6-week-old mallards. Plasma
      corticosterone concentrations showed an increase (P = 0.036) in mallards crated
      in crates of 26 cm height in comparison with control non-crated birds, whereas no
      difference in plasma corticosterone levels was found between mallards crated in
      crates of 20 cm height and control non-crated birds. Lower concentrations of
      plasma triglycerides (P < 0.05) and uric acid (P < 0.05) were found in crated
      mallards in comparison with control non-crated birds; the height of the crates
      had no effect. Mallards crated in crates of 26 cm height also exhibited a higher
      (P = 0.032) plasma lactate dehydrogenase concentration in comparison with control
      non-crated birds, whereas no difference (P > 0.05) was found in lactate
      dehydrogenase concentrations in mallards crated in crates of 20 cm height. Our
      results suggest that crating mallards in lower crates (20 cm) may be less
      stressful than keeping them in crates allowing vertical movements of the birds. 

PMID- 23964993
TI  - Extended Ni(III) oxyhalide perovskite derivatives: Sr2NiO3X (X = F, Cl).
AB  - Extended layered oxyhalide compounds, Sr2NiO3X (X = F, Cl), with the square
      pyramidal coordination around the trivalent nickel ions in the low spin state (S
      = 1/2), are successfully synthesized by a high-pressure and high-temperature
      reaction. Both these compounds crystallize in the n = 1 Ruddlesden-Popper type
      structure, but the difference of halogen anions incorporated dictate the anion
      site ordering patterns and the magnetic ground states. Sr2NiO3F adopts the
      tetragonal cell in the space group I4/mmm (a = b = 3.79125(2) A and c =
      13.13754(9) A), with O/F anions being disordered at the apical sites, while the
      crystal structure of Sr2NiO3Cl is described in the tetragonal space group P4/nmm
      (a = b = 3.85566(1) A and c = 14.43240(6) A) with O/Cl anions being fully ordered
      at the apical sites. Additionally, Sr2NiO3Cl undergoes a long-range
      antiferromagnetic order below TN = 33 K, while the fluorine counterpart does not
      exhibit a long-range ordering but spin glass transition at T(SG) = 11 K. In light
      of the positive Weiss temperatures for both X = F and Cl, the unpaired electron
      likely occupies a d(xy) orbital. Namely, the superexchange interaction mediated
      by d(xy)-Oppi-d(xy) in the NiO2 basal plane is antiferromagnetic, while the
      direct exchange interaction between d(xy)-d(xy) along the diagonal directions is
      ferromagnetic. The origin of spin glass behavior observed in X = F is probably
      due to randomness of the direct d(xy)-d(xy) bonds caused by off-centering nickel
      ions and O/F site disordering.

PMID- 23964994
TI  - Variability of skin autofluorescence measurement over 6 and 12 weeks and the
      influence of benfotiamine treatment.
AB  - BACKGROUND: Measurements of skin autofluorescence (SAF) allow for a simple and
      noninvasive quantification of tissue advanced glycation end-products (AGEs), a
      marker linked to the risk of diabetes complications. The aim of this study was to
      test the repeatability of SAF over 6 and 12 weeks and to test whether
      benfotiamine, a thiamine prodrug suggested to reduce AGEs formation under
      hyperglycemic conditions, is able to attenuate SAF when administered over 6
      weeks. PATIENTS AND METHODS: In a double-blind, placebo-controlled, randomized,
      crossover study, 22 patients with type 2 diabetes mellitus (T2DM) received 900
      mg/day benfotiamine or placebo for 6 weeks (washout period of 6 weeks between).
      At the beginning and at the end of each treatment period, SAF was assessed in the
      fasting state, as well as 2, 4, and 6 h following a mixed test meal. RESULTS: The
      respective intra-individual and inter-individual variability of fasting SAF was
      6.9% and 24.5% within 6 weeks and 10.9% and 23.1% within 12 weeks. The respective
      variability calculated for triplicate comparisons was 9.9% and 27.7%. A short
      term therapy with benfotiamine did not influence SAF significantly, nor did we
      find a significant postprandial SAF increase. CONCLUSIONS: In patients with T2DM,
      repeated, timely spaced SAF measurements have an intra-subject variability of
      below 11%. Using these data, sample sizes were calculated for interventional
      studies aiming at reducing SAF. Benfotiamine treatment for 6 weeks did not
      significantly influence SAF; for this, a longer-term therapy is probably needed.

PMID- 23964995
TI  - Synthesis of a preorganized hybrid macrobicycle with distinct amide and amine
      clefts: tetrahedral versus spherical anions binding studies.
AB  - A new C3v symmetric amido-amine hybrid macrobicycle, L is synthesized toward
      anion recognition in its protonated states. L contains tri-amide and tetra-amine
      clefts separated by p-phenylene spacers. The solid-state structure of methanol
      encapsulated L exhibits an overall cavity length of ~12.0 A where the amide and
      amine -NH protons are converged toward the center of the respective cavities.
      Conformational analysis of L in solution is established by NOESY NMR. Anion
      binding of [H3L](3+) with spherical (Cl(-), Br(-), I(-)) and tetrahedral (ClO4(
      ), SO4(2-)) anions are carried out by isothermal titration calorimeter in
      dimethylsulfoxide. The association of halides with [H3L](3+) is endothermic and
      entropy driven. However, association of tetrahedral anions is exothermic in
      nature and both entropy- and enthalpy-driven. The overall association constants
      show the following order: HSO4(-) > Br(-)> Cl(-) ~ ClO4(-). Single crystal X-ray
      structures of ClO4(-) and Br(-) complexes of protonated L show encapsulation of
      ClO4(-) in the amide cleft of [H2L](2+) (complex 1) and encapsulation of Br(-) in
      the ammonium cleft of [H3L](3+) (complex 2). Further, preorganization of L toward
      encapsulation of spherical and tetrahedral anions is established by comparing its
      amide, amine, and overall cavity dimensions with 1 and 2.

PMID- 23964996
TI  - Who benefits from treatment for executive dysfunction after brain injury?
      Negative effects of emotion recognition deficits.
AB  - Deficits in emotion recognition, a crucial aspect of social cognition, are common
      after serious brain injury, as are executive deficits. Since social cognition and
      executive function are considered to be separate constructs, our first aim was to
      examine the presence of emotion recognition problems in brain injury patients
      with dysexecutive problems. We studied 65 brain injury patients of mixed
      aetiology participating in a randomised controlled trial evaluating the effects
      of a multifaceted treatment for executive dysfunction (Spikman, Boelen, Lamberts,
      Brouwer, & Fasotti, 2010 ) and 84 matched controls with a test for emotion
      recognition. Results showed that, in patients with acquired brain injury
      exhibiting executive deficits, emotion recognition deficits are also present.
      Male patients are more impaired than female patients, irrespective of aetiology.
      Our second aim was to investigate whether emotion recognition problems negatively
      predict the results of the treatment programme. Pre-treatment emotion recognition
      performance significantly predicted resumption of roles in daily life (Role
      Resumption List; RRL) and performance on an ecologically valid test for everyday
      executive functioning (Executive Secretarial Task; EST) post-treatment and, in
      addition, interfered negatively with treatment condition. Moreover, worse pre
      treatment emotion recognition skills affect the learning of compensatory
      strategies for executive dysfunction negatively, whereas pre-treatment
      dysexecutive deficits do not. 

PMID- 23964997
TI  - Habit reversal training in trichotillomania: guide for the clinician.
AB  - Trichotillomania (hair-pulling disorder) involves repetitive hair pulling that
      can cause significant distress and impairment in functioning. Both children and
      adults suffer from the disorder. Habit reversal training (HRT) is the
      trichotillomania treatment with the most empirical support. HRT begins with
      developing an in-depth understanding of the client's unique pulling behaviors.
      The major components of HRT can then be carried out in a way that targets the
      client's specific needs. These include awareness training and self-monitoring,
      stimulus control and competing response procedures. Within each of these
      components the client learns to recognize his or her pulling urges, avoid
      situations in which pulling is more likely and adopt behaviors that can be used
      instead of pulling. Future work will involve evaluating the efficacy of adding
      therapy models such as mindfulness meditation in order to further enhance the
      effectiveness of HRT, and studying the long-term efficacy of HRT for children and
      adults. 

PMID- 23964998
TI  - WholeCellViz: data visualization for whole-cell models.
AB  - BACKGROUND: Whole-cell models promise to accelerate biomedical science and
      engineering. However, discovering new biology from whole-cell models and other
      high-throughput technologies requires novel tools for exploring and analyzing
      complex, high-dimensional data. RESULTS: We developed WholeCellViz, a web-based
      software program for visually exploring and analyzing whole-cell simulations.
      WholeCellViz provides 14 animated visualizations, including metabolic and
      chromosome maps. These visualizations help researchers analyze model predictions
      by displaying predictions in their biological context. Furthermore, WholeCellViz
      enables researchers to compare predictions within and across simulations by
      allowing users to simultaneously display multiple visualizations. CONCLUSION:
      WholeCellViz was designed to facilitate exploration, analysis, and communication
      of whole-cell model data. Taken together, WholeCellViz helps researchers use
      whole-cell model simulations to drive advances in biology and bioengineering.

PMID- 23964999
TI  - Helium nanodroplet isolation and infrared spectroscopy of the isolated ion-pair 1
      ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide.
AB  - The ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide
      was vaporized at 420 K, and the ion-pair constituents were entrained in a beam of
      liquid He nanodroplets and cooled to 0.4 K. The vapor pressure was optimized such
      that each He droplet picked up a single ion-pair from the gas phase. Infrared
      spectroscopy in the CH stretch region reveals bands that are assigned to intact
      ion-pairs on the basis of comparisons to ab initio harmonic frequency
      computations of 23 low energy isomers. The He droplet spectrum is consistent with
      a weighted sum of the computed harmonic spectra, in which the weights are
      determined from ab initio computations of the relative free energies at 420 K.
      Anharmonic resonance polyads in the CH stretch region are treated explicitly,
      which improves the agreement between the experiment and computed spectra for ion
      pairs. For isomers having a strong cation...anion hydrogen bonding interaction,
      the imidazolium C(2)-H stretch fundamental is shifted to lower energy and into
      resonance with the overtones and combination bands of the imidazolium ring
      stretching modes, resulting in a spectral complexity in the CH stretch region
      that is fully resolved in the He droplet spectrum. The assignment of the infrared
      spectrum to ion-pairs is confirmed through polarization spectroscopy measurements
      that reveal the permanent electric dipole moment of the He-solvated species to be
      11 +/- 2 D. The computed permanent electric dipole moments for the low energy
      isomers of the [emim(+)][Tf2N(-)] ion-pairs fall in the range 9-13 D, whereas the
      computed dipole moments of decomposition products of the ionic liquid are less
      than 4.3 D. 

PMID- 23965001
TI  - Thermal probe maskless lithography for 27.5 nm half-pitch Si technology.
AB  - Thermal scanning probe lithography is used for creating lithographic patterns
      with 27.5 nm half-pitch line density in a 50 nm thick high carbon content organic
      resist on a Si substrate. The as-written patterns in the poly phthaladehyde
      thermal resist layer have a depth of 8 nm, and they are transformed into high
      aspect ratio binary patterns in the high carbon content resist using a SiO2 hard
      mask layer with a thickness of merely 4 nm and a sequence of selective reactive
      ion etching steps. Using this process, a line-edge roughness after transfer of
      2.7 nm (3sigma) has been achieved. The patterns have also been transferred into
      50 nm deep structures in the Si substrate with excellent conformal accuracy. The
      demonstrated process capabilities in terms of feature density and line-edge
      roughness are in accordance with today's requirements for maskless lithography,
      for example for the fabrication of extreme ultraviolet (EUV) masks. 

PMID- 23965000
TI  - Investigating the properties of the hemodynamic response function after mild
      traumatic brain injury.
AB  - Abstract Although several functional magnetic resonance imaging (fMRI) studies
      have been conducted in human models of mild traumatic brain injury (mTBI), to
      date no studies have explicitly examined how injury may differentially affect
      both the positive phase of the hemodynamic response function (HRF) as well as the
      post-stimulus undershoot (PSU). Animal models suggest that the acute and semi
      acute stages of mTBI are associated with significant disruptions in metabolism
      and to the microvasculature, both of which could impact on the HRF. Therefore,
      fMRI data were collected on a cohort of 30 semi-acute patients with mTBI (16
      males; 27.83+/-9.97 years old; 13.00+/-2.18 years of education) and 30 carefully
      matched healthy controls (HC; 16 males; 27.17+/-10.08 years old; 13.37+/-2.31
      years of education) during a simple sensory-motor task. Patients reported
      increased cognitive, somatic, and emotional symptoms relative to controls,
      although no group differences were detected on traditional neuropsychological
      examination. There were also no differences between patients with mTBI and
      controls on fMRI data using standard analytic techniques, although mTBI exhibited
      a greater volume of activation during the task qualitatively. A significant
      Group*Time interaction was observed in the right supramarginal gyrus, bilateral
      primary and secondary visual cortex, and the right parahippocampal gyrus. The
      interaction was the result of an earlier time-to-peak and positive magnitude
      shift throughout the estimated HRF in patients with mTBI relative to HC. This
      difference in HRF shape combined with the greater volume of activated tissue may
      be indicative of a potential compensatory mechanism to injury. The current study
      demonstrates that direct examination and modeling of HRF characteristics beyond
      magnitude may provide additional information about underlying neuropathology that
      is not available with more standard fMRI analyses. 

PMID- 23965002
TI  - [Abdominal compartment syndrome - review of current knowledge, diagnosis and
      management].
AB  - This overview of the historical development in the definition of terms intra
      abdominal hypertension and abdominal compartment syndrome focuses on the wide
      range of compartment syndromes and presents the issue of surgical or conservative
      management in the care for patients affected by the above-mentioned pathological
      abdominal conditions.

PMID- 23965003
TI  - [Internal carotid artery surgery under locoregional anaesthesia at the Department
      of Surgery in Pilsen during the past 10 years (2002-2011)].
AB  - During the ten-year period (2002-2011), carotid artery surgery was performed in
      1164 patients, with a mean age of 68 years (44 to 86 years), at the Department of
      Surgery, University Hospital in Pilsen. In total, 1304 procedures on internal
      carotid arteries were performed, and the ratio of procedures in men and women was
      912/392. The ratio of procedures in asymptomatic vs. symptomatic findings was
      938/366. The ratio of patients with unilateral vs. bilateral damage to the
      internal carotid artery was 930/234. All surgical procedures on internal carotid
      arteries were performed under locoregional anaesthesia. From the total number of
      internal carotid artery operations (1304), the 30-day mortality and morbidity
      rate was 1.46%.

PMID- 23965004
TI  - [Leriche's syndrome].
AB  - INTRODUCTION: Leriche's syndrome is defined as atherosclerotic occlusion of the
      infrarenal aorta and/or the iliac axis. It is associated with claudications or
      critical limb ischaemia and erectile dysfunction in men. MATERIAL AND METHODS:
      Twenty patients with Leriche's syndrome were operated on at the Department of
      Surgery, University Hospital in Pilsen between 2008 and 2012. There were 6 women
      and 14 men of average age 60.3 years (41-76 years). Three patients were in group
      C and 17 in group D according to the Trans-Atlantic Inter-Society Classification
      IIb (TASC IIb). Fifteen patients suffered from chronic claudication or rest pain,
      five patients had acute limb ischaemic symptomatology. Aortobifemoral bypass with
      subsequent anti-aggregation therapy was the only treatment option. RESULTS:
      Primary 30-day patency was 100%. 30-day postoperative mortality was 5% (one
      patient died of acute myocardial infarction). Two patients died in two and four
      years after the reconstruction (10%) due to cerebral ischaemia and
      bronchopneumonia. Only one extremity amputation was performed within the five
      year interval after vascular reconstruction. All aortobifemoral reconstructions
      were patent in two months to five years after the operation. We had to manage
      only one false aneurysm in the groin three years after the aortobifemoral
      reconstruction. CONCLUSION: Aortobifemoral bypass is a method of choice for the
      treatment of Leriche's syndrome. Endovascular treatment is suitable for patients
      with severe comorbidities.

PMID- 23965005
TI  - [Mediastinitis after esophageal perforation].
AB  - INTRODUCTION: Assessment of therapy in patients with mediastinal infection
      resulting from esophageal perforation. MATERIAL AND METHODS: Retrospective (2008
      2012) processing of a group of surgically treated patients. The aspects assessed
      were aetiology, the surgical methods applied and the length of therapy. RESULTS:
      The total number of patients treated was 16. In 8 cases, the aetiology was
      iatrogenic (3 cases of leaking esophageal anastomosis in consequence of resection
      of the esophagus, 2 cases of perforation after fundoplication, 1 case of
      esophageal cardiomyotomy, and 2 cases of perforation during endoscopy). In 4
      patients, the aetiology was spontaneous perforation, impacted foreign bodies
      caused difficulties to 3 patients, and the last cause was acid corrosive
      esophagitis. A stent was applied in all the patients at the site of the defect.
      The mediastinitis was drained through the access from thoracotomy or left
      thoracolaparotomy, respectively (8 cases), or by combination of
      laparotomy/laparostomy and pleural drainage (5 cases). Pleural (in 3 cases) and
      neck (1 case) drainage meant minimum intervention. Esophagectomy was not carried
      out in any of the patients. 4 patients died. The average period of time for which
      the stent was left in situ was 53.7 days; the average time of hospitalization in
      surviving patients was 53.4 days. CONCLUSION: Stent application does not show any
      difference regarding patients' survival (25% mortality), but enables shortening
      the total therapy time and, predominantly, preserving the native esophagus.

PMID- 23965006
TI  - [Kidney transplantation from donors dying of methanol intoxication].
AB  - INTRODUCTION: Intoxicated patients represent only a minimum of the total number
      of cadaveric donors; however, their significance within the transplant program in
      the Czech Republic has recently been emphasized in connection with the so-called
      methanol affair. MATERIAL AND METHODS: A retrospective analysis of methanol
      poisoned patients who were declared brain-dead and subsequently underwent organ
      removal for transplantation purposes in the University Hospital Ostrava was
      performed. In cooperation with other transplant centres (Institute for Clinical
      and Experimental Medicine, Transplant Centre of the University Hospital Hradec
      Krailove, Centre for Cardiovascular and Transplantation Surgery in Brno) the
      graft function, postoperative morbidity and mortality was evaluated. RESULTS:
      During the study period (since September 2012), organs from three brain-dead
      donors as a result of methanol intoxication were retrieved in the Transplant
      Centre of the University Hospital Ostrava. Subsequently, six kidneys were
      transplanted (3 males, 3 females). Postoperative complications occurred in two
      patients (33.3%), one patient died (16.7%). In one case (16.7%), the graft
      failed. None of the graft recipients developed clinical or laboratory signs of
      methanol poisoning. CONCLUSION: Death due to methanol intoxication is not a
      contraindication to organ donation, graft function and patient survival being
      comparable to organs from non-intoxicated donors.

PMID- 23965007
TI  - [Combined procedure of pulmonary resection and radiofrequency ablation of lung
      tumours - case reports].
AB  - The authors present two case reports to describe the possibility of performing a
      combined procedure when dealing with lung cancer in patients who are not
      indicated for radical surgery. The combination of pulmonary resection and
      radiofrequency ablation thus opens a new possibility for a quality extension of
      active life.

PMID- 23965008
TI  - [Double gallbladder - a rare congenital variation].
AB  - Double gallbladder, a congenital anatomic variation, represents approximately 2%
      of all congenital anatomic variations of the gastrointestinal tract, its
      incidence amounting to about 25 in 100 000. It has several types classified
      according to Boyden's criteria. The diagnostic method of first choice is
      ultrasonography. When the patient has no health complaints and
      cholecystolithiasis is present, no special treatment measures are required. The
      treatment option in symptomatic cholecystolithiasis is laparoscopic
      cholecystectomy. Only a few cases of double or triple gallbladder, in contrast to
      the high number of cholecystectomies, have been published in literature. The
      authors present a case of double gallbladder where the diagnosis was established
      more than three years after laparoscopic cholecystectomy

PMID- 23965009
TI  - The Interaction of Spatial and Object Pathways: Evidence from Balint's Syndrome.
AB  - An earlier report described a patient (RM) with bilateral parietal damage who
      showed severe binding problems between shape and color and shape and size
      (Friedman-Hill, Robertson, & Treisman, 1995). When shown two different-colored
      letters, RM reported a large number of illusory conjunctions (ICs) combining the
      shape of one letter with the color of the other, even when he was looking
      directly at one of them and had as long as 10 sec to respond. The lesions also
      produced severe deficits in locating and reaching for objects, and difficulty in
      seeing more than one object at a time, resulting in a neuropsychological
      diagnosis of Balint's syndrome or dorsal simultanagnosia. The pattern of deficits
      supported predictions of Treisman's Feature Integration Theory (FIT) that the
      loss of spatial information would lead to binding errors. They further suggested
      that the spatial information used in binding depends on intact parietal function.
      In the present paper we extend these findings and examine other deficits in RM
      that would be predicted by FIT. We show that: (1) Object individuation is
      impaired, making it impossible for him correctly to count more than one or two
      objects, even when he is aware that more are present. (2) Visual search for a
      target defined by a conjunction of features (requiring binding) is impaired,
      while the detection of a target defined by a unique feature is not. Search for
      the absence of a feature (0 among Qs) is also severely impaired, while search for
      the presence (Q among 0s) is not. Feature absence can only be detected when all
      the present features are bound to the nontarget items. (3) RM's deficits cannot
      be attributed to a general binding problem: binding errors were far more likely
      with simultaneous presentation where spatial information was required than with
      sequential presentation where time could be used as the medium for binding. (4)
      Selection for attention was severely impaired, whether it was based on the
      position of a marker or on some other feature (color). (5) Spatial information
      seems to exist that RM cannot access, suggesting that feature binding relies on a
      relatively late stage where implicit spatial information is made explicitly
      accessible. The data converge to support our conclusions that explicit spatial
      knowledge is necessary for the perception of accurately bound features, for
      accurate attentional selection, and for accurate and rapid search for a
      conjunction of features in a multiitem display. It is obviously necessary for
      directing attention to spatial locations, but the consequences of impairments in
      this ability seem also to affect object selection, object individuation, and
      feature integration. Thus, the functional effects of parietal damage are not
      limited to the spatial and attentional problems that have long been described in
      patients with Balint's syndrome. Damage to parietal areas also affects object
      perception through damage to spatial representations that are fundamental for
      spatial awareness. 

PMID- 23965010
TI  - Brain activity associated with syntactic incongruencies in words and pseudo
      words.
AB  - Event-related brain potentials (EMS) were recorded while normal German subjects
      read either simple declarative sen- tences made up from real German words, or
      sentences that contained German pseudo-words instead of nouns and verbs. The verb
      (pseudo-verb) of the sentences disagreed in number with the subject noun (pseudo
      noun) in 50% of the sentences. The subjects had the task either to read the
      sentences for an interspersed memory test (memory condition, pseudeword sentences
      only) or to make a syntactic judgment after each real-word/pseudo-word sentence.
      While in the real-word condition a late and widespread positivity resembling the
      previously described syntactic positive shift was found for the disagreeing
      verbs, a negativity with an onset latency of about 300 msec was seen for the
      disagreeing pseudo-verbs. In the pseudo-word conditions no positivity followed
      the initial negativity. This dissociation of negative and positive waves
      occurring in response to morphosyntactic mismatches by the pseudo/real-word
      manipulation suggests that the positive shift is a concomitant of a recomputation
      routine initiated to account for the number incongruency. This routine is based
      upon the semantics of the sentence and therefore is not observed in the pseudo
      word conditions. The earlier negativity, on the other hand, appears to be a more
      direct index of morphosyntactic incongruency. 

PMID- 23965011
TI  - Dopaminergic modulation of working memory for spatial but not object cues in
      normal humans.
AB  - It appears that functionally segregated visual pathways exist in the primate
      brain for the processing of visuospatial versus nonspatial information.
      Functional segregation has been demonstrated for the early associative processing
      of sensory information but may also exist at higher levels of cognitive analysis.
      Namely, connections between the dorsal visual system and dorsolateral prefrontal
      cortex (PFC) appear to mediate spatial working memory, which is modulated by
      dopamine receptor fields in the principal sulcal region of the PFC. It is
      speculated that nonspatial working memory may be modulated within connections
      between ventral visual processing regions and the inferior convexity of the PFC.
      Whether dopamine facilitates nonspatial memory through connections between the
      ventral visual system and ventral PFC has not been examined. In this study,
      normal humans completed spatial and nonspatial working memory tasks under
      pharmacological challenges with a dopamine receptor agonist (bromocriptine) and
      antagonist (haloperidol) in a double-blind placebcxontrolled repeated measures
      design. Findings indicated facilitation of spatial delayed working memory
      functions by bromocriptine and impairment of spatial working memory functions by
      haloperidol. Neither drug was effective in manipulating nonspatial memory
      performance. Control tasks were included to measure drug effects on basic
      sensorimotor and attentional processes. Findings suggest that separate processing
      mechanisms for remembering "What" versus "Where" an object is may exist at
      structural, but also neurochemical, levels in the human brain. 

PMID- 23965012
TI  - Egocentric and allocentric constraints in the expression of patterns of interlimb
      coordination.
AB  - Tasks that are easy when performed in isolation become difficult when performed
      simultaneously in the upper and/or lower limbs. This observation points to basic
      CNS constraints in the organization of patterns of interlimb coordination. The
      present studies provide evidence for the existence of two basic coordinative
      constraints whose effects may be additive under certain conditions. On one hand,
      the egocentric constraint denotes a general preference for moving the limbs
      toward or away from the longitudinal axis of the body in a symmetrical fashion
      and is of primary importance during the coordination of homologous limbs. On the
      other hand, the allocentric constraint refers to a general preference to move the
      limbs in the same direction in extrinsic space and pertains to the coordination
      of nonhomologous limbs (eg., various combinations of the upper and lower limbs).
      In the present context, constraints are considered as expressions of basic
      features of CNS operation that give way to preferred coordination patterns to
      which the system is naturally drawn or biased. The identification and description
      of these constraints is considered of critical importance to obtain a better
      understanding of the control of coordination patterns. 

PMID- 23965013
TI  - Brain activation in young and older adults during implicit and explicit
      retrieval.
AB  - Positron emission tomography was used to study regional cerebral blood flow
      (H2(15)O method) in groups of young and older adults during implicit and explicit
      retrieval, following a procedure devised by Squire et al. (1992). At study,
      subjects were exposed to four lists of words. Following list presentation,
      subjects were presented with three-letter word stems under four conditions: (1)
      silent viewing, (2) completion of word stems that could not form words from the
      study list, with the instruction to provide the first word that came to mind
      (baseline), (3) completion of word stems, half of which could form words from the
      study list, with the instruction to provide the first word that came to mind
      (priming), and (4) completion of word stems, half of which could form words from
      the study list, with the instruction to use the stems as cues for recall of list
      words (memory). The behavioral data indicated an agerelated deficit in cued
      recall that was reduced in priming. Both age groups showed a similar decrease of
      blood flow in right posterior cortex during priming relative to baseline. During
      cued recall, bilateral increases of blood flow were observed in prefrontal cortex
      and anterior cingulate gyrus for both age groups. The young adults showed
      selective increases of activity in left cerebellum and Wernicke's area, whereas
      the older adults showed a selective bilateral activation in the perirhinal region
      of the medial-temporal cortex during cued recall. The results suggest a simiiar
      biological basis of priming in both age groups: a decrease in the neural activity
      required to process a particular stimulus during a subsequent encounter compared
      with a previous one. In addition, the importance of prefrontal regions for
      conscious retrieval was substantiated and extended to late adulthood. Finally,
      the agedifferential activations observed during cued recall were discussed
      relative to prominent concepts in the current literature on cognitive aging
      (e.g., speed of processing, self-initiated operations, cross-modal recoding). 

PMID- 23965014
TI  - Time-related changes in neural systems underlying attention and arousal during
      the performance of an auditory vigilance task.
AB  - Vigilance behavior, or watch keeping, involves the focusing of attention on the
      detection of subtle changes in the environment that occur over a long period of
      time. We investigated the time course of changes in brain activity during the
      continuous performance of a 60-min auditory vigilance task. The task required the
      detection of an intensity drop that occurred in 5% of the auditory stimuli. Six 1
      min samples of cerebral blood flow (CBF) and electroencephalographic (EEG)
      activity were obtained at l0-min intervals during the vigilance performance.
      Changes in CBF were measured by means of positron emission tomography (PET).
      Performance data (hits, false alarms, reaction time) were analyzed across six 10
      min blocks. Eight healthy male volunteers participated in the study. During the
      60-min test, the number of correct detections (hits) did not change, but both the
      reaction time and EEG activity in the theta (4 to 7 Hz) range progressively
      increased across testing. CBF in several subcortical structures (thalamus,
      substantia innominata, and putamen) and cortical areas (ventrolateral,
      dorsolateral, and orbital frontal cortex; parietal cortex; and temporal cortex)
      decreased as a function of time-on-task; changes in the cortical regions were
      limited to the right hemisphere. Blood flow also decreased in the temporalis
      muscles. At the same time, CBF increased in several visual cortical areas
      including the left and right fusiform gyri. Furthermore, the thalamic blood-flow
      response co-varied with that in the substantia innominata, the ponto
      mesencephalic tegmentum, and the anterior cingulate cortex. The right
      ventrolateral-frontal blood-flow response covaried with that in the right
      parietal, orbitofrontal, and dorsolateral frontal cortex. 'Iko main conclusions
      are drawn from the obtained data. First, we suggest that the observed time
      related changes in reaction time, EEG activity, and blood flow in the temporalis
      muscles are related to changes in the level of arousal (alertness) and that CBF
      changes in the thalamus-related neural circuitry represent a brain correlate of
      such changes. Second, we speculate that time-related CBF decreases in cortical
      regions of the right hemisphere underlie a shift from controlled to automatic
      attentional processing of the auditory stimuli. 

PMID- 23965015
TI  - Localizing arithmetic processes in the brain: evidence from a transient deficit
      during cortical stimulation.
AB  - Although substantial progress has been made in characterizing the cognitive
      processes involved in simple arithmetic, the localization of these processes in
      the brain is not yet well understood. In this article we consider the
      localization of a specific arithmetic process, the retrieval of arithmetic table
      facts from memory. We report a single-patient study in which cortical stimulation
      was used to create transient disruption of brain activity in localized regions of
      the cortex. We show that stimulation at a left parietal site impaired performance
      on simple multiplication problems and further that the impairment reflected
      stimulation-induced disruption of arithmetic fact retrieval. Our findings support
      the hypothesis (e.g., Warrington, 1982) that the left parietal lobe is implicated
      in the arithmetic fact retrieval process. 

PMID- 23965016
TI  - Exact parallel maximum clique algorithm for general and protein graphs.
AB  - A new exact parallel maximum clique algorithm MaxCliquePara, which finds the
      maximum clique (the fully connected subgraph) in undirected general and protein
      graphs, is presented. First, a new branch and bound algorithm for finding a
      maximum clique on a single computer core, which builds on ideas presented in two
      published state of the art sequential algorithms is implemented. The new
      sequential MaxCliqueSeq algorithm is faster than the reference algorithms on both
      DIMACS benchmark graphs as well as on protein-derived product graphs used for
      protein structural comparisons. Next, the MaxCliqueSeq algorithm is parallelized
      by splitting the branch-and-bound search tree to multiple cores, resulting in
      MaxCliquePara algorithm. The ability to exploit all cores efficiently makes the
      new parallel MaxCliquePara algorithm markedly superior to other tested
      algorithms. On a 12-core computer, the parallelization provides up to 2 orders of
      magnitude faster execution on the large DIMACS benchmark graphs and up to an
      order of magnitude faster execution on protein product graphs. The algorithms are
      freely accessible on http://commsys.ijs.si/~matjaz/maxclique.

PMID- 23965017
TI  - Chitooligosaccharides are converted to N-acetylglucosamine by N-acetyl-beta
      hexosaminidase from Stenotrophomonas maltophilia.
AB  - The Stenotrophomonas maltophilia k279a (Stm) Hex gene encodes a polypeptide of
      785 amino acid residues, with an N-terminal signal peptide. StmHex was cloned
      without signal peptide and expressed as an 83.6 kDa soluble protein in
      Escherichia coli BL21 (DE3). Purified StmHex was optimally active at pH 5.0 and
      40  degrees C. The Vmax, Km and kcat/Km for StmHex towards chitin hexamer were
      10.55 nkat (mg protein)(-1), 271 MUM and 0.246 s(-1) mM(-1), while the kinetic
      values with chitobiose were 30.65 nkat (mg protein)(-1), 2365 MUM and 0.082 s(-1)
      mM(-1), respectively. Hydrolytic activity on chitooligosaccharides indicated that
      StmHex was an exo-acting enzyme and yielded N-acetyl-D-glucosamine (GlcNAc) as
      the final product. StmHex hydrolysed chitooligosaccharides (up to hexamer) into
      GlcNAc within 60 min, suggesting that this enzyme has potential for use in large
      scale production of GlcNAc from chitooligosaccharides.

PMID- 23965019
TI  - The role of timing in motor program representation.
AB  - A motor program is the representation in memory that controls the sequential
      structure of a motor skill. The present research was an attempt to determine the
      degree to which the timing and sequencing components of a motor skill are related
      in motor-program representation in a serial key-pressing task. Four groups
      practiced on event sequences varying in the form of the inherent temporal
      structure. Following training subjects attempted to execute the event sequences
      from memory as quickly as possible where the maintenance of the inherent temporal
      structure was not required. Under speed instructions the entire sequence was
      speeded up, but performance was still strongly influenced by the overall temporal
      structure acquired during training. The results suggested that the relative
      timing of events is an integral part of motor program representation,
      particularly in skills involving rhythmic timing structures. This paper is based
      on a doctoral dissertation at the University of Oregon, Dr. Steven W. Keele,
      sponsor. The research was supported by a contract from the Office of Naval
      Research, Contract No. N00014-67-A-0046-004 to S. W. Keele. 

PMID- 23965018
TI  - Systematic review and meta-analysis of the association between childhood
      overweight and obesity and primary school diet and physical activity policies.
AB  - Obesity is a major public health concern and there are increasing calls for
      policy intervention. As obesity and the related health conditions develop during
      childhood, schools are being seen as important locations for obesity prevention,
      including multifaceted interventions incorporating policy elements. The objective
      of this systematic review was to evaluate the effects of policies related to diet
      and physical activity in schools, either alone, or as part of an intervention
      programme on the weight status of children aged 4 to 11 years. A comprehensive
      and systematic search of medical, education, exercise science, and social science
      databases identified 21 studies which met the inclusion criteria. There were no
      date, location or language restrictions. The identified studies evaluated a range
      of either, or both, diet and physical activity related policies, or intervention
      programmes including such policies, using a variety of observational and
      experimental designs. The policies were clustered into those which sought to
      affect diet, those which sought to affect physical activity and those which
      sought to affect both diet and physical activity to undertake random effects meta
      analysis. Within the diet cluster, studies of the United States of America
      National School Lunch and School Breakfast Programs were analysed separately;
      however there was significant heterogeneity in the pooled results. The pooled
      effects of the physical activity, and other diet related policies on BMI-SDS were
      non-significant. The multifaceted interventions tended to include policy elements
      related to both diet and physical activity (combined cluster), and although these
      interventions were too varied to pool their results, significant reductions in
      weight-related outcomes were demonstrated. The evidence from this review suggests
      that, when implemented alone, school diet and physical activity related policies
      appear insufficient to prevent or treat overweight or obesity in children,
      however, they do appear to have an effect when developed and implemented as part
      of a more extensive intervention programme. Additional evidence is required
      before recommendations regarding the focus of policies can be made and therefore,
      increased effort should be made to evaluate the effect of policies and policy
      containing intervention programmes upon weight status.

PMID- 23965020
TI  - Sequential Effects of Foreperiod Duration as a function of the Frequency of
      Foreperiod Repetitions.
AB  - An examination of sequential effects of foreperiod duration in reaction time
      tasks suggests a description of the subjects' strategy in terms of a tendency to
      expect foreperiod repetitions. The present experiment examined what factors
      influence this basic tendency. Two foreperiod distributions differing in the
      frequency of repetitions (33 and 66%) but with the same frequency of individual
      foreperiods were used. In both cases faster reaction times coincided with
      foreperiod repetitions. Important differences appeared nevertheless between the
      two foreperiod distributions; reaction times for repetitions were faster when
      repetitions were frequent than when they were not, and repetitions of the same
      fore-period more than once led to further reaction-time decreases only when
      foreperiod repetitions were frequent. The tendency to expect repetitions varied
      from trial to trial in a way which depended on long-term factors such as the
      frequency with which the expected foreperiod duration coincided with the
      foreperiod actually presented. 

PMID- 23965021
TI  - Self-acceptance and disconfirming feedback as influences upon performance of a
      gross motor skill.
AB  - High and low self-acceptance subjects (N= 120) were tested under conditions of
      disconfirming feedback above and below performance expectancy on a gross motor
      skill. Subjects in the high and low disconfirming feedback groups received
      confirming feedback after Trials 1 to 4 and disconfirming feedback after Trials 5
      to 10. Discrepant feedback as an experimental manipulation did not affect the
      performance of either group of subjects. The results are discussed in terms of
      cognitive dissonance theory. 

PMID- 23965022
TI  - Preferred tempo of motor performance.
AB  - The magnitude of individual differences in within-subject variability in
      performance of repetitive movements at a self-paced tempo was investigated.
      Subjects (N = 150) performed an accuracy task involving consecutive arm swings at
      an individually chosen tempo. Odd-even and serial half reliability coefficients
      for within-subject variances (r =.72, .66) were significant at the .01 level.
      Also, statistically significant correlation coefficients ranging from .70 to .76
      were found between subjects' mean response times and within-subject variances.
      With the effect of mean response times partialled out, the reliability
      coefficients for within-subject variances were reduced (r = .41, .30) but were
      still statistically significant (p<.01). The findings indicated that individual
      differences in within-subject variance were present to a moderate degree. 

PMID- 23965023
TI  - Muscular fatigue and the learning and performance of a motor control task.
AB  - Four groups of 12 female college students performed a pursuit-rotor task during
      learning under one of four conditions of exercising the muscles of the limb used
      in the task: (a) no muscular exercise, (b) low-fatiguing, (c) medium-fatiguing,
      and (d) high-fatiguing muscular exercise. All four groups were tested 48 hr later
      on the same pursuit-rotor task with no exercise interpolated between the ten 20
      sec trials. Differences in the performances among the four groups were not
      statistically significant on either the first or the second day alone or when the
      data of the two days were combined. The data appear to support the hypothesis of
      an inverted-U or inverted-J model relating performance (and learning) to muscular
      fatigue in motor-control tasks. 

PMID- 23965024
TI  - Relative effects of three knowledge of results treatments on coincidence
      anticipation performance.
AB  - The relative effects of three knowledge of results (KR) treatments on performance
      of a complex coincidence-anticipation task requiring speed and accuracy were
      studied. Male volunteers (n=75) were assigned to one of three treatments: no KR,
      quantitative KR, or qualitative KR. No significant differences in the performance
      of treatment groups were found. It was suggested that the task itself may have
      provided enough information for fairly accurate performance. 

PMID- 23965025
TI  - The role of visual feedback in short-term motor memory.
AB  - Previous experiments examining the role of feedback in short-term motor memory
      have permitted vision not only during the movement, but also of the starting and
      terminal positions. In the present experiment, presence or absence of vision (a)
      prior to the start of the movement, and (b) during the movement were
      independently manipulated in a 2 * 2 between-subjects design, using 15 subjects
      per group. During prior vision subjects were able to see the terminal position of
      the movement they were about to make. Results, showing that vision during the
      movement did not contribute to performance, were taken as providing evidence
      against the Adams (1971) closed-loop theory of motor learning. 

PMID- 23965026
TI  - Observational learning of a motor skill.
AB  - Female subjects (n = 180) observed live model demonstrations that were presented
      either (a) before practice, (b) prior to and midway through practice, or (c)
      midway through practice. The effects of the temporal spacing of model
      presentations on subject's subsequent performance was examined. Also, subjects
      performed before the experimenter only, a model audience, or an audience
      consisting of strangers, with an additional no-audience control condition. The no
      audience control group had significantly lower performances than all other
      groups. Evidence for the effectiveness of temporal spacing of the model
      presentation was indicated, but no significant differences were found for the
      audience factor. 

PMID- 23965027
TI  - The serial-position effect in short-term motor retention.
AB  - The existence of inter-item interference was demonstrated in an experiment
      investigating proactive inhibition in motor short-term memory. Blindfolded
      subjects moved a slide to a stop and then attempted to replace the slide in the
      correct (criterion) location with the stop removed. Independent variables were
      positions recalled in addition to the criterion (zero or four) and retention
      interval length (5 or 50 sec). While retention loss on the criterion position was
      found only for the group with four additional positions and a 50-sec retention
      interval, analysis of recall error at each position for subjects given a five
      item sequence and a 5-sec retention interval indicated a serial-position effect.
      Implications of the findings for the role of cognitive processes in motor short
      term memory were discussed. 

PMID- 23965028
TI  - Evaluation of the phenotypic test and genetic analysis in the detection of
      glucose-6-phosphate dehydrogenase deficiency.
AB  - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is particularly
      prevalent in historically malaria-endemic countries. Although most individuals
      with G6PD deficiency are asymptomatic, deficiency can result in acute haemolytic
      anaemia after exposure to oxidative agents. A reliable test is necessary for
      diagnosing the deficiency to prevent an acute haemolytic crisis following, for
      example, anti-malarial treatment. The aim of this study was to investigate which
      method was the best predictor of this disorder. METHODS: The present study
      investigated four G6PD activity detections (fluorescence spot (FS),
      methaemoglobin reduction (MR), biochemical and cytochemical test). These methods
      accompanied with mutation analysis of blood samples were taken from 295
      apparently healthy individuals with unknown G6PD deficiency status. RESULTS:
      Molecular characterization of 295 Thai adults revealed an overall prevalence of
      14.2%. The G6PD Viangchan (871 G>A) was the most common (83.3%), followed by G6PD
      Mahidol (487G>A) (11.9%), and G6PD Union (1360 C>T) (4.8%). There were two cases
      of G6PD deficiency carrying the double mutations of Viangchan (871G > A)-Mahidol
      (487G > A) and Viangchan (871G > A)-Union (1360C > T). In comparison, the
      prevalence of G6PD deficiency was 6.1% by FS test and 7.1% by MR test. G6PD
      activity was 11 +/- 2.5 IU/gHb in non-deficient females (mean +/- SD), and 10.9
      +/- 0.6 IU/gHb in non-deficient males. The upper and lower limit cut-off points
      for partial and severe deficiency in adults were 5.7 IU/gHb (60% of the normal
      mean) and 0.95 IU/gHb (10% of the normal mean), respectively. All hemizygote,
      homozygote and double mutations were associated with severe enzyme deficiency
      (the residual enzyme activity <10% of the normal mean), whereas only 14.3% of the
      heterozygote mutations showed severe enzyme deficiency. Based on the cut-off
      value <5.7 IU/gHb, the quantitative G6PD assay diagnosed 83% of cases as G6PD
      deficient. Using a cut-off number of negative cell >20% in the cytochemical assay
      to define G6PD deficiency, the prevalence of G6PD deficiency was closest to the
      molecular analysis (12.9% G6PD-deficient) compared to the others methods.
      CONCLUSION: The cytochemical method is a significant predictor of this disease,
      while FS and MR test are recommended for the detection of severe G6PD deficiency
      in developing countries.

PMID- 23965029
TI  - Pathways to poor educational outcomes for HIV/AIDS-affected youth in South
      Africa.
AB  - A recent systematic review of studies in the developing world has critically
      examined linkages from familial HIV/AIDS and associated factors such as poverty
      and child mental health to negative child educational outcomes. In line with
      several recommendations in the review, the current study modelled relationships
      between familial HIV/AIDS, poverty, child internalising problems, gender and four
      educational outcomes: non-enrolment at school, non-attendance, deficits in grade
      progression and concentration problems. Path analyses reveal no direct
      associations between familial HIV/AIDS and any of the educational outcomes.
      Instead, HIV/AIDS-orphanhood or caregiver HIV/AIDS-sickness impacted indirectly
      on educational outcomes via the poverty and internalising problems that they
      occasioned. This has implications for evidence-based policy inferences. For
      instance, by addressing such intervening variables generally, rather than by
      seeking to target families affected by HIV/AIDS, interventions could avoid
      exacerbating stigmatisation, while having a more direct and stronger impact on
      children's educational outcomes. This analytic approach also suggests that future
      research should seek to identify causal paths, and may include other intervening
      variables related to poverty (such as child housework and caring
      responsibilities) or to child mental health (such as stigma and abuse), that are
      linked to both familial HIV/AIDS and educational outcomes.

PMID- 23965031
TI  - Differential adsorption of small molecules in spatially functionalized porous
      silicon nanostructures.
AB  - An experimental approach to rapidly quantify the relative affinity of a small
      molecule analyte for two different surfaces is described. The method uses optical
      measurements of high surface area porous Si thin films that contain two spatially
      distinct surface chemistries. The chemistries are placed on the walls of the ~10
      nm diameter pores of the porous Si film by means of microdroplet patterning,
      where a chemical resist is drop-coated on the porous Si sample to define distinct
      regions across the plane of the chip. In this work, the two chemistries consist
      of a hydrophilic silicon oxide surface and a hydrophobic methyl-terminated
      silicon surface. Detection is achieved by simultaneous optical reflectance
      measurements of both regions, where the reflectance spectrum contains a
      convolution of the Fabry-Perot interference spectrum of both the oxide and the
      methyl-grafted layers. The differential partitioning of a test analyte (2
      acetoxybenzoic acid or diphenyl ether) from aqueous solution is determined from
      the Fourier transform of the optical interference spectrum. The approach is rapid
      and nondestructive, and it can be performed on a small sample volume as a means
      to quantify the partition behavior of small molecules. 

PMID- 23965030
TI  - Lack of significant association between mutations of KCNJ10 or FOXI1 and SLC26A4
      mutations in Pendred syndrome/enlarged vestibular aqueducts.
AB  - BACKGROUND: Pendred syndrome is a common autosomal recessive disorder causing
      deafness. Features include sensorineural hearing impairment, goitre, enlarged
      vestibular aqueducts (EVA) and occasionally Mondini dysplasia. Hearing impairment
      and EVA may occur in the absence of goitre or thyroid dyshormonogensis in a
      condition known as non-syndromic EVA. A significant number of patients with
      Pendred syndrome and non-syndromic EVA show only one mutation in SLC26A4. Two
      genes, KCNJ10, encoding an inwardly rectifying potassium channel and FOXI1, a
      transcriptional factor gene, are thought to play a role in the disease
      phenotypes. METHODS: Using Polymerase Chain Reaction and Sanger sequencing, sixty
      eight patients with monoallelic mutations of SLC26A4 were tested for mutations in
      KCNJ10 and FOXI1. RESULTS: Two variants were observed in the KCNJ10 gene,
      p.Arg271Cys in three patients and p.Arg18Gln in one patient; only one variant,
      p.Arg123Trp was observed in the FOXI1 gene in a single patient. Both p.Arg271Cys
      and p.Arg18Gln are likely to be polymorphisms as judged by their frequency in the
      general population. CONCLUSION: Therefore we found no evidence for a significant
      association between mutations of KCNJ10 and FOXI1 with SLC26A4. It was also
      observed that the variant, p.Arg271Cys in KCNJ10, previously thought to have a
      protective effect against seizure susceptibility, was found in a patient with
      Pendred syndrome with co-existing epilepsy.

PMID- 23965032
TI  - Variable D-dimer thresholds for diagnosis of clinically suspected acute pulmonary
      embolism.
AB  - BACKGROUND: Computed tomography pulmonary angiography (CTPA) is frequently
      requested using diagnostic algorithms for suspected pulmonary embolism (PE). For
      suspected deep vein thrombosis, it was recently shown that doubling the D-dimer
      threshold in patients with low pretest probability safely decreased the number of
      ultrasonograms. We evaluated the safety and efficiency of a similar strategy in
      patients with suspected PE. METHODS: We performed a post-hoc analysis of 2213
      consecutive patients of two cohort studies with suspected PE who were managed
      according to current standards: PE ruled out in case of unlikely probability
      (Wells rule <= 4 points) and a D-dimer level < 0.5 MUg mL(-1) . CTPA was
      performed in all other cases. All patients were followed for 3 months. We
      calculated 3-month venous thromboembolism (VTE) incidence and the number of
      required CTPAs for selective D-dimer thresholds in patients with low clinical
      probability (< 2 points, D-dimer threshold < 1.0 MUg mL(-1) ) and intermediate
      probability (2-6 points, D-dimer threshold < 0.5 MUg mL(-1) ). RESULTS: Using
      standard management, PE could be excluded without CTPA in 26% of patients, with a
      3-month VTE incidence of 0.88% (95% confidence interval [CI] 0.29-2.1%). Using
      selective D-dimer thresholds, PE could be excluded without CTPA in 36% of
      patients, with a 3-month VTE incidence of 2.1% (95% CI 1.2-3.4%) in patients
      managed without CTPA, an increase of 1.2 percentage points (95% CI -0.3 to 2.2).
      CONCLUSIONS: Applying selective D-dimer thresholds reduces the need for CTPA by
      11 percentage points but is associated with an increased failure rate.
      Prospective studies should evaluate the safety and net clinical benefit of this
      approach.

PMID- 23965033
TI  - Central response to painful electrical esophageal stimulation in well-defined
      patients suffering from functional chest pain.
AB  - BACKGROUND: Functional chest pain (FCP) of presumed esophageal origin is
      considered a common cause for chest pain in which central nervous system
      hyperexcitability is thought to play an important role. We aimed to compare
      cerebral responses with painful esophageal stimuli between FCP patients and
      healthy subjects (HS). METHODS: Thirteen patients with FCP (seven females, mean
      age 50.4 +/- 7.5 years) and 15 HS (eight females, mean age 49.1 +/- 12.9 years)
      were enrolled. Inclusion criteria consisted of typical chest pain, normal
      coronary angiogram, and normal upper gastrointestinal evaluation. Electrical
      stimulations evoking the pain threshold were applied in the distal esophagus,
      while cortical evoked potentials were recorded from the scalp. Pain scores,
      resting electroencephalogram (EEG), evoked potential characteristics and brain
      electrical sources to pain stimulation were compared between groups. KEY RESULTS:
      No differences were seen between patients and HS regarding (i) pain thresholds
      (patients: 20.1 +/- 7.4 mA vs HS: 22.4 +/- 8.3 mA, all P > 0.05), (ii) resting
      EEG (P > 0.05), (iii) evoked brain potential latencies (N2: patients 181.7 +/-
      25.7 mS vs HS 182.2 +/- 25.8 mS, all P > 0.05) and amplitudes (N2P2: patients 8.2
      +/- 7.2 MUV vs HS: 10.1 +/- 3.4 MUV, all P > 0.05), (iv) topography (P > 0.05),
      and (v) brain source location (P > 0.05). CONCLUSIONS & INFERENCES: No
      differences in activation of brain areas to painful esophageal stimulation were
      seen in this group of well characterized patients with FCP compared with sex- and
      age-matched HS. The mechanism of pain in FCP and whether it originates in the
      esophagus remains unsolved.

PMID- 23965034
TI  - Novel bis[5-(fluoren-2-yl)thiophen-2-yl]benzothiadiazole end-capped with
      carbazole dendrons as highly efficient solution-processed nondoped red emitters
      for organic light-emitting diodes.
AB  - A series of novel red-emitting bis[5-(fluoren-2-yl)thiophen-2-yl]benzothiadiazole
      cored dendrimers containing carbazole dendrons up to the third generation are
      synthesized. Their photophysical, thermal, electrochemical, and
      electroluminescent properties as nondoped solution-processed red light-emitters
      for OLEDs are investigated. By using carbazole dendrons as the end caps, we are
      able to reduce the crystallization and retain the high emissive ability of a
      planar fluorescent core in the solid state as well as improve the thermal
      stability of the material. These dendrimers show a bright-red fluorescence and
      can form morphologically stable amorphous thin films with glass-transition
      temperatures as high as 283  degrees C. Simple structured solution-processed
      OLEDs using these materials as hole-transporting nondoped emitters and BCP as the
      hole-blocking layer emit a stable red color around 622-645 nm, with high
      luminance efficiencies (up to 4.80 cd A(-1) at 1.2 mA cm(-2)) and CIE coordinates
      of (0.65, 0.33), which are close to the pure red color. 

PMID- 23965035
TI  - 4-[18F]Fluoro-m-hydroxyphenethylguanidine: a radiopharmaceutical for quantifying
      regional cardiac sympathetic nerve density with positron emission tomography.
AB  - 4-[(18)F]Fluoro-m-hydroxyphenethylguanidine ([(18)F]4F-MHPG, [(18)F]1) is a new
      cardiac sympathetic nerve radiotracer with kinetic properties favorable for
      quantifying regional nerve density with PET and tracer kinetic analysis. An
      automated synthesis of [(18)F]1 was developed in which the intermediate 4
      [(18)F]fluoro-m-tyramine ([(18)F]16) was prepared using a diaryliodonium salt
      precursor for nucleophilic aromatic [(18)F]fluorination. In PET imaging studies
      in rhesus macaque monkeys, [(18)F]1 demonstrated high quality cardiac images with
      low uptake in lungs and the liver. Compartmental modeling of [(18)F]1 kinetics
      provided net uptake rate constants Ki (mL/min/g wet), and Patlak graphical
      analysis of [(18)F]1 kinetics provided Patlak slopes Kp (mL/min/g). In
      pharmacological blocking studies with the norepinephrine transporter inhibitor
      desipramine (DMI), each of these quantitative measures declined in a dose
      dependent manner with increasing DMI doses. These initial results strongly
      suggest that [(18)F]1 can provide quantitative measures of regional cardiac
      sympathetic nerve density in human hearts using PET. 

PMID- 23965037
TI  - Mosaic-like monolayer of graphene oxide sheets decorated with tetrabutylammonium
      ions.
AB  - We report the fabrication of mosaic-like monolayers of graphene oxide (G-O)
      coated with tetrabutylammonium ions (TBA) using a simple spin-coating method. The
      TBA-coated G-O (TG-O) sheets were prepared by "spontaneous exfoliation" of
      graphite oxide intercalated with tetrabutylammonium hydroxide (TBAOH) in the wet
      state, without the need for sonication. Mosaic-like monolayers could be formed on
      a variety of substrates such as Si wafer (coated with the thin native oxide),
      SiO2/Si wafer, graphene grown by chemical vapor deposition and then transferred
      on SiO2/Si wafer, Au film on Si wafer, and Cu foil. The mosaic-like monolayer of
      TG-O was compared with monolayers of G-O and TG-O prepared using a Langmuir
      Blodgett (LB) trough. The formation of the mosaic-like TG-O monolayer films was
      attributed to (1) weakening of the electrostatic repulsion between G-O sheets by
      TBA, and (2) prevention of the overlap and stacking of TG-O sheets by disruption
      of the hydrogen bonding between the basal plane of one sheet and the basal plane
      or edge of another, by adsorbed TBA. External reflection FTIR spectroscopy showed
      that spectral features of the mosaic-like monolayer of TG-O made by simple spin
      coating were the same as those for the monolayer fabricated using the LB
      assembly, indicating the same spatial orientations of functional groups. This
      study provides a very simple route to a complete monolayer of G-O without the
      need for an LB trough. 

PMID- 23965036
TI  - The future of basal insulin.

PMID- 23965038
TI  - Hard and soft metal complexes of calix[4]-bis-monothiacrown-5: X-ray and NMR
      studies of discrete homodinuclear complexes and a heteromultinuclear network.
AB  - Endocyclic homodinuclear complexation and endo/exocyclic heteronuclear networking
      of calix[4]-bis-monothiacrown-5 (L) are reported. First, dipotassium(I) and
      disilver(I) complexes of L were isolated and their solid state structures
      characterized. To probe the complexation behavior for these same systems in
      solution, the competition between potassium(I) and silver(I) for L was monitored
      by (1)H NMR. Potassium(I) showed a higher affinity to L than silver(I) both in
      the solid and solution states. The reaction of L with KI in the presence of HgI2
      afforded a two-dimensional coordination polymer with the endocyclic
      dipotassium(I) complex linked by an exocyclic mercury(II) iodide cluster
      backbone. 

PMID- 23965039
TI  - Testing the effects of peer socialization versus selection on alcohol and
      marijuana use among treated adolescents.
AB  - This study examined the relative influence of peer socialization and selection on
      alcohol and marijuana use among 106 adolescents who received a brief
      intervention. Adolescents were recruited between 2003 and 2007 and followed for
      12 months as part of a SAMHSA-funded study. Cross-lagged panel models using four
      assessment points examined the longitudinal relationship between adolescent
      substance use and peer substance involvement separately for alcohol and
      marijuana. Consistent with community studies, there was evidence of both peer
      socialization and peer selection for alcohol use, and only evidence of peer
      selection for marijuana use. Implications for research and intervention are
      discussed. 

PMID- 23965040
TI  - Mortality, causes of death and risk factors for death among primary amphetamine
      users in the Swedish criminal justice system.
AB  - This study examined mortality and predictors of death in 1,396 primary
      amphetamine users (85% males) who were interviewed with the Addiction Severity
      Index in the Swedish criminal justice system during 2000-2006 and followed
      through 2008. Forty-nine clients deceased (standardized mortality ratio 4.1 [3.0
      5.4]), at least 84% of deaths were violent or drug-related (12% suicides), and
      Cox regression analysis indicated that death was associated with frequent use of
      sedatives and less frequent use of amphetamine. No female deaths were observed;
      death and male gender were associated in binary analysis. Implications for
      diagnostics and treatment are discussed. 

PMID- 23965041
TI  - Intergenerational continuity of substance use.
AB  - Guided by rigorous methodology and a life-course perspective, the goal of this
      research is to address a gap in current knowledge on whether, when, and how
      strongly intergenerational continuity of substance use exists when examining age
      equivalent and developmentally specific stages of the life course. Annual self
      reported substance use measures were analyzed from a prospective, longitudinal,
      and nationally representative sample that originally consisted of 1,725
      respondents and their families, who were then interviewed over a 27-year period
      from 1977 to 2004. Findings from multilevel random-intercept regression models
      provide support for intergenerational continuity when substance use occurs in
      emerging adulthood but not when limited to adolescence. Implications,
      limitations, and future research directions are discussed. 

PMID- 23965042
TI  - Synthetic entry into 1-phosphono-3-azabicyclo[3.1.0]hexanes.
AB  - 3-Azabicyclo[3.1.0]hex-2-en-1-yl phosphonates were prepared in a five-step
      reaction route from beta-ketophosphonates. The key steps in this sequence are an
      atom-transfer radical cyclization and an unforeseen lithium-halogen exchange with
      n-BuLi. The cyclization reaction proceeds with excellent diastereoselectivity.
      The resulting cyclic imines were reduced, and 3-azabicyclo[3.1.0]hexan-1-yl
      phosphonates were obtained. 

PMID- 23965043
TI  - Conservative spine care: opportunities to improve the quality and value of care.
AB  - Low back pain (LBP) has received considerable attention from researchers and
      health care systems because of its substantial personal, social, work-related,
      and economic consequences. A narrative review was conducted summarizing data
      about the epidemiology, care seeking, and utilization patterns for LBP in the
      adult US population. Recommendations from a consensus of clinical practice
      guidelines were compared to findings about the current state of clinical practice
      for LBP. The impact of the first provider consulted on the quality and value of
      care was analyzed longitudinally across the continuum of episodes of care. The
      review concludes with a description of recently published evidence that has
      demonstrated that favorable health and economic outcomes can be achieved by
      incorporating evidence-informed decision criteria and guidance about entry into
      conservative low back care pathways.

PMID- 23965044
TI  - The addition of the Charlson Comorbidity Index to the GRACE Risk Prediction Index
      improves prediction of outcomes in acute coronary syndrome.
AB  - Patients with cardiovascular disease have increased risk of poor outcomes when
      coexisting illnesses are present. Clinicians, administrators, and health services
      researchers utilize risk adjustment indices to stratify patients for various
      outcomes. The GRACE Risk Prediction Index (GRPI) was developed to risk stratify
      patients who experienced an acute coronary syndrome (ACS) event. GRPI does not
      account for the presence of comorbid conditions. The objective of this study was
      to compare the ability of the GRPI and the Charlson Comorbidity Index (CCI), used
      independently or combined, to predict mortality or secondary coronary events in
      patients admitted for ACS. Data were obtained from an academic health system's
      ACS registry. Outcomes included inpatient and 6-month postdischarge mortality and
      occurrence of secondary cardiovascular events or revascularization procedures.
      Logistic regression derived C statistics for CCI, GRPI, and CCI-GRPI predictive
      models for each outcome. Likelihood ratio tests determined the contribution of
      CCI when added to GRPI models. Complete data were available for 1202 patients.
      The GRPI model had the greatest C statistic when predicting inpatient mortality
      (0.73); the GRPI-CCI combined model C statistic was 0.81 when predicting death
      during the follow-up period; and C statistics for all 3 models were similar in
      predicting secondary events (0.57-0.60). The likelihood ratio analysis
      demonstrated that adding CCI to GRPI models was beneficial primarily for
      predicting secondary events. CCI is a useful addition to GRPI when predicting
      future cardiac-related events or mortality after an ACS event. It is an
      acceptable alternative to the GRPI model if data to construct GRPI are not
      available.

PMID- 23965045
TI  - Impact of hospital variables on case mix index as a marker of disease severity.
AB  - Case mix index (CMI) has become a standard indicator of hospital disease severity
      in the United States and internationally. However, CMI was designed to calculate
      hospital payments, not to track disease severity, and is highly dependent on
      documentation and coding accuracy. The authors evaluated whether CMI varied by
      characteristics affecting hospitals' disease severity (eg, trauma center or not).
      The authors also evaluated whether CMI was lower at public hospitals than private
      hospitals, given the diminished financial resources to support documentation
      enhancement at public hospitals. CMI data for a 14-year period from a large
      public database were analyzed longitudinally and cross-sectionally to define the
      impact of hospital variables on average CMI within and across hospital groups.
      Between 1996 and 2007, average CMI declined by 0.4% for public hospitals, while
      rising significantly for private for-profit (14%) and nonprofit (6%) hospitals.
      After the introduction of the Medicare Severity Diagnosis Related Group (MS-DRG)
      system in 2007, average CMI increased for all 3 hospital types but remained
      lowest in public vs. private for-profit or nonprofit hospitals (1.05 vs. 1.25 vs.
      1.20; P<0.0001). By multivariate analysis, teaching hospitals, level 1 trauma
      centers, and larger hospitals had higher average CMI, consistent with a marker of
      disease severity, but only for private hospitals. Public hospitals had lower CMI
      across all subgroups. Although CMI had some characteristics of a disease severity
      marker, it was lower across all strata for public hospitals. Hence, caution is
      warranted when using CMI to adjust for disease severity across public vs. private
      hospitals.

PMID- 23965046
TI  - Characteristics of acute care utilization of a Delaware adult sickle cell disease
      patient population.
AB  - Sickle cell disease (SCD) is an inherited blood disorder that is chronic in
      nature and manifests itself through many facets of the patient's life.
      Comprehensive specialty centers have the potential to reduce health care costs
      and improve the quality of care for patients who have chronic medical conditions
      such as heart failure and SCD. The purpose of this practice inquiry was to
      analyze de-identified data for acute care episodes involving SCD in order to
      create a detailed picture of acute care utilization for adult patients in
      Delaware with SCD from 2007 to 2009. Gaining a better understanding of acute care
      utilization for adults with SCD may provide evidence to improve access to high
      quality health care services for this vulnerable patient population in the state
      of Delaware.

PMID- 23965047
TI  - A flexible count data model to fit the wide diversity of expression profiles
      arising from extensively replicated RNA-seq experiments.
AB  - BACKGROUND: High-throughput RNA sequencing (RNA-seq) offers unprecedented power
      to capture the real dynamics of gene expression. Experimental designs with
      extensive biological replication present a unique opportunity to exploit this
      feature and distinguish expression profiles with higher resolution. RNA-seq data
      analysis methods so far have been mostly applied to data sets with few replicates
      and their default settings try to provide the best performance under this
      constraint. These methods are based on two well-known count data distributions:
      the Poisson and the negative binomial. The way to properly calibrate them with
      large RNA-seq data sets is not trivial for the non-expert bioinformatics user.
      RESULTS: Here we show that expression profiles produced by extensively-replicated
      RNA-seq experiments lead to a rich diversity of count data distributions beyond
      the Poisson and the negative binomial, such as Poisson-Inverse Gaussian or Polya
      Aeppli, which can be captured by a more general family of count data
      distributions called the Poisson-Tweedie. The flexibility of the Poisson-Tweedie
      family enables a direct fitting of emerging features of large expression
      profiles, such as heavy-tails or zero-inflation, without the need to alter a
      single configuration parameter. We provide a software package for R called
      tweeDEseq implementing a new test for differential expression based on the
      Poisson-Tweedie family. Using simulations on synthetic and real RNA-seq data we
      show that tweeDEseq yields P-values that are equally or more accurate than
      competing methods under different configuration parameters. By surveying the tiny
      fraction of sex-specific gene expression changes in human lymphoblastoid cell
      lines, we also show that tweeDEseq accurately detects differentially expressed
      genes in a real large RNA-seq data set with improved performance and
      reproducibility over the previously compared methodologies. Finally, we compared
      the results with those obtained from microarrays in order to check for
      reproducibility. CONCLUSIONS: RNA-seq data with many replicates leads to a
      handful of count data distributions which can be accurately estimated with the
      statistical model illustrated in this paper. This method provides a better fit to
      the underlying biological variability; this may be critical when comparing groups
      of RNA-seq samples with markedly different count data distributions. The
      tweeDEseq package forms part of the Bioconductor project and it is available for
      download at http://www.bioconductor.org.

PMID- 23965048
TI  - Nanostructured conformal hybrid solar cells: a promising architecture towards
      complete charge collection and light absorption.
AB  - We introduce hybrid solar cells with an architecture consisting of an
      electrodeposited ZnO nanorod array (NRA) coated with a conformal thin layer (<50
      nm) of organic polymer-fullerene blend and a quasi-conformal Ag top contact
      (Thin/NR). We have compared the performance of Thin/NR cells to conventional
      hybrid cells in which the same NRAs are completely filled with organic blend
      (Thick/NR). The Thin/NR design absorbs at least as much light as Thick/NR cells,
      while charge extraction is significantly enhanced due to the proximity of the
      electrodes, resulting in a higher current density per unit volume of blend and
      improved power conversion efficiency. The NRAs need not be periodic or aligned
      and hence can be made very simply. 

PMID- 23965049
TI  - Leave the pay review body to do its job.

PMID- 23965063
TI  - Trusts take a uniform approach to help patients recognise staff roles.

PMID- 23965067
TI  - Will funding injection avert a winter crisis?

PMID- 23965068
TI  - Wright angle - Stephen Wright's monthly take on nursing in the news.

PMID- 23965074
TI  - Opportunity for progress.
AB  - The Cavendish review into HCAs and support workers highlighted the contribution
      such staff make to patient care, and called for them to be supported with
      improved training, career opportunities and status. This article shows how some
      enlightened employers are leading the way in developing their HCA workforce.

PMID- 23965075
TI  - Specialist support.
AB  - People with ulcerative colitis of Crohn's disease often develop the conditions in
      their teens or early twenties. Specialist nurses help people cope and get on with
      their lives. Access is improving, but one in five young patients still miss out
      on specialist nursing care.

PMID- 23965076
TI  - Development down under.
AB  - The RCN Clinical Leadership Programme was introduced to Australia ten years ago.
      More than 350 South Australian nurses and midwives have completed it, some
      travelling huge distances to attend sessions. Reported benefits include
      confidence to lead and deal with change.

PMID- 23965090
TI  - Stop patient care funds being siphoned off by PFI investors.

PMID- 23965091
TI  - Long shifts are a factor in apathy, compassion fatigue and poor care.

PMID- 23965092
TI  - Cancer survivors need support from healthcare professionals.

PMID- 23965093
TI  - Welcoming workers with HIV will benefit the health service.

PMID- 23965094
TI  - Laws relating to informed consent in clinical trials.

PMID- 23965096
TI  - Toxicology had to be the focus, not psychological care.

PMID- 23965097
TI  - Role of the military community mental health nurse.
AB  - AIM: To understand the role and effect of a community mental health nurse (CMHN)
      deployed to work with military personnel during sea-based operations. METHOD:
      Semi-structured interviews were conducted to ascertain Royal Navy aircraft
      carrier military unit commanders' perceptions and experiences of the CMHN's role.
      FINDINGS: Three mutually inclusive components are necessary to ensure successful
      integration of the CMHN: familiarity, trust and credibility. CONCLUSION: For
      CMHNs to function successfully and provide mental health care to sea-based
      military personnel, they need to demonstrate familiarity, trust and credibility.
      This will enhance uptake of mental health services among military personnel and
      ensure they are fit for service.

PMID- 23965098
TI  - Removal of foreign bodies from children's ears: a nurse-led clinic.
AB  - This article presents an account of the rationale for and the introduction of a
      change in practice. The successful removal of foreign bodies from children's ears
      requires appropriate skills and experience. While traditionally a role for junior
      doctors, removal of foreign bodies from children's ears at the ear, nose and
      throat outpatient clinic at Birmingham Children's Hospital was associated with a
      low success rate. Therefore, it was proposed that an experienced advanced nurse
      practitioner would carry out this task in an attempt to improve patient outcomes.
      A database of outcomes was maintained and compared with those from a doctor-led
      clinic at Nottingham University Hospitals NHS Trust. The results highlight the
      benefits of nurse-led removal of foreign bodies from children's ears. 

PMID- 23965099
TI  - Progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP), or Steele-Richardson-Olszewski syndrome, is
      a rare, progressive neurodegenerative condition with cognitive and motor
      involvement. Diagnosis can be challenging as some people do not display the
      classic symptoms of the condition and there are no specific investigations to
      confirm diagnosis. Timely discussions and access to symptom management and
      palliative care services need to be provided from diagnosis throughout the
      disease trajectory to ensure holistic care of people with PSP. 

PMID- 23965100
TI  - Supporting mentors.

PMID- 23965101
TI  - Where the heart is.

PMID- 23965102
TI  - Renal care roles are so rewarding.

PMID- 23965105
TI  - Student life - hearing it from service users.

PMID- 23965106
TI  - Regulation moves a step closer.

PMID- 23965109
TI  - Turning learning into action.

PMID- 23965111
TI  - Triumph of teamwork.

PMID- 23965112
TI  - Rising to the challenge.

PMID- 23965113
TI  - 'I am now doing things that I did not think I would be able to do'.

PMID- 23965114
TI  - Too hot... or too cold?

PMID- 23965115
TI  - Legal advice.

PMID- 23965116
TI  - Interprofessional, simulation-based training in end of life care communication: a
      pilot study.
AB  - This paper reports on the process and outcomes of a study, designed to pilot the
      use of interprofessional, simulation-based training in end of life care
      communication. Participants comprised 50 final year medicine, nursing,
      physiotherapy and pharmacy students. Learning methods included observation of
      role play and facilitated, interactive group discussion. A Likert scale rating
      questionnaire was used to evaluate the impact of the learning experience.
      Evaluation data revealed that students were supportive of interprofessional
      learning and could recognise its benefits. The results indicated self-perceived
      improvements in knowledge, skills, confidence and competence when dealing with
      challenging end of life care communication situations. Comparison of pre- and
      post-intervention scores revealed a statistically significant positive change in
      the students' perceptions about their level of knowledge (Z = -5.887, p = 0.000).
      The reported benefits need to be balanced against design and delivery issues that
      proved labour and resource intensive. Economic evaluation is worthy of further
      consideration.

PMID- 23965117
TI  - Fast energy relaxation of hot carriers near the Dirac point of graphene.
AB  - We investigate energy relaxation of hot carriers in monolayer and bilayer
      graphene devices, demonstrating that the relaxation rate increases significantly
      as the Dirac point is approached from either the conduction or valence band. This
      counterintuitive behavior appears consistent with ideas of charge puddling under
      disorder, suggesting that it becomes very difficult to excite carriers out of
      these localized regions. These results therefore demonstrate how the peculiar
      properties of graphene extend also to the behavior of its nonequilibrium
      carriers. 

PMID- 23965118
TI  - What Is Special about Face Recognition? Nineteen Experiments on a Person with
      Visual Object Agnosia and Dyslexia but Normal Face Recognition.
AB  - In order to study face recognition in relative isolation from visual processes
      that may also contribute to object recognition and reading, we investigated CK, a
      man with normal face recognition but with object agnosia and dyslexia caused by a
      closed-head injury. We administered recognition tests of up right faces, of
      family resemblance, of age-transformed faces, of caricatures, of cartoons, of
      inverted faces, and of face features, of disguised faces, of perceptually
      degraded faces, of fractured faces, of faces parts, and of faces whose parts were
      made of objects. We compared CK's performance with that of at least 12 control
      participants. We found that CK performed as well as controls as long as the face
      was upright and retained the configurational integrity among the internal facial
      features, the eyes, nose, and mouth. This held regardless of whether the face was
      disguised or degraded and whether the face was represented as a photo, a
      caricature, a cartoon, or a face composed of objects. In the last case, CK
      perceived the face but, unlike controls, was rarely aware that it was composed of
      objects. When the face, or just the internal features, were inverted or when the
      configurational gestalt was broken by fracturing the face or misaligning the top
      and bottom halves, CK's performance suffered far more than that of controls. We
      conclude that face recognition normally depends on two systems: (1) a holistic,
      face-specific system that is dependent on orientationspecific coding of second
      order relational features (internal), which is intact in CK and (2) a part-based
      object-recognition system, which is damaged in CK and which contributes to face
      recognition when the face stimulus does not satisfy the domain-specific
      conditions needed to activate the face system. 

PMID- 23965119
TI  - Face-specific processing in the human fusiform gyrus.
AB  - The perception of faces is sometimes regarded as a specialized task involving
      discrete brain regions. In an attempt to identi$ face-specific cortex, we used
      functional magnetic resonance imaging (fMRI) to measure activation evoked by
      faces presented in a continuously changing montage of common objects or in a
      similar montage of nonobjects. Bilateral regions of the posterior fusiform gyrus
      were activated by faces viewed among nonobjects, but when viewed among objects,
      faces activated only a focal right fusiform region. To determine whether this
      focal activation would occur for another category of familiar stimuli, subjects
      viewed flowers presented among nonobjects and objects. While flowers among
      nonobjects evoked bilateral fusiform activation, flowers among objects evoked no
      activation. These results demonstrate that both faces and flowers activate large
      and partially overlapping regions of inferior extrastriate cortex. A smaller
      region, located primarily in the right lateral fusiform gyrus, is activated
      specifically by faces. 

PMID- 23965120
TI  - How do monkeys look at faces?
AB  - Facial displays are an important form of social communication in nonhuman
      primates. Clues to the information conveyed by faces are the temporal and spatial
      characteristics of ocular viewing patterns to facial images. The present study
      compares viewing patterns of four rhesus monkeys (Macaca mulatta) to a set of 1-
      and 3-sec video segments of conspecific facial displays, which included open
      mouth threat, lip-smack, yawn, fear-grimace, and neutral profile. Both static and
      dynamic video images were used. Static human faces displaying open-mouth threat,
      smile, and neutral gestures were also presented. Eye position was recorded with a
      surgically implanted eye-coil. The relative perceptual salience of the eyes, the
      midface, and the mouth across different expressive gestures was determined by
      analyzing the number of eye movements associated with each feature during static
      and dynamic presentations. The results indicate that motion does not
      significantly affect the viewing patterns to expressive facial displays, and when
      given a choice, monkeys spend a relatively large amount of time inspecting the
      face, especially the eyes, as opposed to areas surrounding the face. The
      expressive nature of the facial display also affected viewing patterns in that
      threatening and fear-related displays evoked a pattern of viewing that differed
      from that recorded during the presentation of submissive-related facial displays.
      From these results we conclude that (1) the most important determinant of the
      visual inspection patterns of faces is the constellation of physiognomic features
      and their configuration, but not facial motion, (2) the eyes are generally the
      most salient facial feature, and (3) the agonistic or affiliative dimension of an
      expressive facial display can be delineated on the basis of viewing patterns. 

PMID- 23965121
TI  - Common Blood Flow Changes across Visual Tasks: I. Increases in Subcortical
      Structures and Cerebellum but Not in Nonvisual Cortex.
AB  - Nine positron emission tomography (PET) studies of human visual information
      processing were reanalyzed to determine the consistency across experiments of
      blood flow increases during active tasks relative to passive viewing of the same
      stimulus array. No consistent blood flow increases were found in cerebral cortex
      outside of the visual system, but increases were seen in the thalamus and
      cerebellum. Although most tasks involve increases in arousal, establishing an
      intention or behavioral goal, setting up control structures for sequencing task
      operations, detecting targets, etc., these operations do not produce blood flow
      increases, detectable with the present methods, in localized cortical regions
      that are common across tasks. Common subcortical regions, however, may be
      involved. A left cerebellar and a medial cerebellar focus reflected motor-related
      processes. Blood flow increases in these regions only occurred in experiments in
      which the subject made an overt response and were largest when the response was
      made in the active but not passive condition. These motor-related processes were
      more complex than simple motor execution, however, since increases were still
      present when the response was made in both the active and passive conditions.
      These cerebellar increases may reflect processes related to response
      selection.Blood flow increases in a right cerebellar region were not motor
      related. Increases were not modulated by the presence or absence of motor
      responses during either the active or passive conditions, and increases were
      sensitive to within-experiment variables that held the motor response constant.
      Increases occurred in both language and nonlanguage tasks and appeared to involve
      a general nonmotor process, but the nature of that process was difficult to
      specify. A right thalamic focus was sensitive to variables related to focal
      attention, suggesting that this region was involved in attentional engagement.
      Right thalamic increases were also correlated over conditions with increases in
      the left and medial cerebellum, perhaps reflecting additional contributions from
      motor-related nuclei receiving cerebellar projections. Blood flow increases in a
      left thalamic focus were completely uncorrelated over conditions with increases
      in the right thalamus, indicating that it was involved in different functions.
      Both the left thalamus and right cerebellum yielded larger blood flow increases
      when subjects performed a complex rather than simple language task, possibly
      reflecting a language-related pathway. Blood flow increases in the left thalamus
      were also observed, however, during nonlanguage tasks. 

PMID- 23965122
TI  - Common Blood Flow Changes across Visual Tasks: II. Decreases in Cerebral Cortex.
AB  - Nine previous positron emission tomography (PET) studies of human visual
      information processing were reanalyzed to determine the consistency across
      experiments of blood flow decreases during active tasks relative to passive
      viewing of the same stimulus array. Areas showing consistent decreases during
      active tasks included posterior cingulate/precuneous (Brodmann area, BA 31/7),
      left (BAS 40 and 39/19) and right (BA 40) inferior parietal cortex, left
      dorsolateral frontal cortex (BA S), left lateral inferior frontal cortex (BA
      10/47), left inferior temporal gyrus @A 20), a strip of medial frontal regions
      running along a dorsal-ventral axis (BAs 8, 9, 10, and 32), and the right
      amygdala. Experiments involving language-related processes tended to show larger
      decreases than nonlanguage experiments. This trend mainly reflected blood flow
      increases at certain areas in the passive conditions of the language experiments
      (relative to a fixation control in which no task stimulus was present) and slight
      blood flow decreases in the passive conditions of the nonlanguage experiments.
      When the active tasks were referenced to the fixation condition, the overall size
      of blood flow decreases in language and nonlanguage tasks were the same, but
      differences were found across cortical areas. Decreases were more pronounced in
      the posterior cingulate/precuneous (BAS 31/7) and right inferior parietal cortex
      (BA 40) during language-related tasks and more pronounced in left inferior
      frontal cortex (BA 10/47) during nonlanguage tasks. Blood flow decreases did not
      generally show significant differences across the active task states within an
      experiment, but a verb-generation task produced larger decreases than a read task
      in right and left inferior parietal lobe (BA 40) and the posterior
      cingulate/precuneous (BA 31/7), while the read task produced larger decreases in
      left lateral inferior frontal cortex (BA 10/47). These effects mirrored those
      found between experiments in the language-nonlanguage comparison. Consistent
      active minus passive decreases may reflect decreased activity caused by active
      task processes that generalize over tasks or increased activity caused by passive
      task processes that are suspended during the active tasks. Increased activity
      during the passive condition might reflect ongoing processes, such as
      unconstrained verbally mediated thoughts and monitoring of the external
      environment, body, and emotional state. 

PMID- 23965123
TI  - Sentence reading: a functional MRI study at 4 tesla.
AB  - In this study, changes in blood oxygenation and volume were monitored while
      monolingual right-handed subjects read English sentences. Our results confirm the
      role of the left peri-sylvian cortex in language processing. Interestingly,
      individual subject analyses reveal a pattern of activation characterized by
      several small, limited patches rather than a few large, anatomically well
      circumscribed centers. Between-subject analyses confirm a lateralized pattern of
      activation and reveal active classical language areas including Broca's area,
      Wernicke's area, and the angular gyms. In addition they point to areas only more
      recently considered as language-relevant including the anterior portion of the
      superior temporal sulcus. This area has not been reliably observed in imaging
      studies of isolated word processing. This raises the hypothesis that activation
      in this area is dependent on processes specific to sentence reading. 

PMID- 23965124
TI  - On the different processing of wholes and parts: a psychophysiological analysis.
AB  - The global precedence hypothesis (Navon, 1977) assumes that the processing of the
      global level of a hierarchical pattern precedes that of the local level. To
      explore further the nature of global and local processing of compound stimuli, we
      recorded the event-related brain potentials (ERPs) associated with ident@ing the
      global and local levels of nonlinguistic compound stimuli in a selective
      attention task. Wile subjects' behavioral responses were similar to those
      observed by Navon (1977), the analyses of ERP data showed that identification of
      the local level elicited longer N2 and P3 peak latencies with enhanced N2 and
      decreased P3 amplitudes relative to the identification of the global level. The
      inconsistency between the global and local levels made N2 and P3 amplitudes more
      negative with longer peak latencies. This interference effect on N2 and P3
      amplitude and P3 latency was stronger on the local level than on the global
      level. The modulation of N2 by the consistency of the global and local levels
      observed in this and the previous (Heinze, Muente, et al., 1994) study suggests
      that the interference effect may be mediated by the early perceptual processing.
      Moreover, we found that the amplitude of an early posterior P1 component was
      modulated by attention to the global and local levels, being larger to the local
      target than to the global one. This PI effect gives no support to the notion that
      the variation of attentional spotlight determines the global precedence effect. 

PMID- 23965126
TI  - [Vacuum-assisted closure as a treatment modality for infrainguinal vascular
      prosthetic graft infection: our experience and take-home message].
AB  - INTRODUCTION: Infection of the prosthetic graft represents one of the biggest
      challenges for practising vascular surgeons. The patient is jeopardized with
      possible future limb loss or, in the most serious cases, even death due to this
      complication. The incidence in the infrainguinal area amounts to a maximum of 6%
      of all arterial surgical procedures. MATERIAL AND METHODS: Between January 2010
      and December 2011, the authors performed a total of 689 vascular surgical
      reconstructions, of which 311 were performed in the infrainguinal area where 7
      cases (2.25%) of graft infection occurred. RESULTS: None of the patients died or
      lost a limb due to this complication. Two patients with an infected infrainguinal
      prosthetic graft were successfully treated with vacuum-assisted closure (VAC)
      system. CONCLUSION: The prosthetic vascular graft infection is the most feared
      complication in vascular surgery. The generally recognized principles of the
      traditional surgical approach are well-known and widely accepted. However, in
      selected cases of infrainguinal vascular prosthetic infection, both the affected
      limb and the patent graft may be saved and successfully treated with the use of
      vacuum-assisted closure.

PMID- 23965125
TI  - Experimental and structural testing module to analyze paralogue-specificity and
      affinity in the Hsp90 inhibitors series.
AB  - We here describe the first reported comprehensive analysis of Hsp90 paralogue
      affinity and selectivity in the clinical Hsp90 inhibitor chemotypes. This has
      been possible through the development of a versatile experimental assay based on
      a new FP-probe (16a) that we both describe here. The assay can test rapidly and
      accurately the binding affinity of all major Hsp90 chemotypes and has a testing
      range that spans low nanomolar to millimolar binding affinities. We couple this
      assay with a computational analysis that allows for rationalization of paralogue
      selectivity and defines not only the major binding modes that relay pan-paralogue
      binding or, conversely, paralogue selectivity, but also identifies molecular
      characteristics that impart such features. The methods developed here provide a
      blueprint for parsing out the contribution of the four Hsp90 paralogues to the
      perceived biological activity with the current Hsp90 chemotypes and set the
      ground for the development of paralogue selective inhibitors. 

PMID- 23965127
TI  - [Impact of anastomotic leakage on oncological outcomes after rectal cancer
      resection].
AB  - INTRODUCTION: The aim of the study was to determine the impact of anastomotic
      leakage on long-term outcomes after curative surgery for rectal cancer. MATERIAL
      AND METHODS: The study included 174 patients who underwent elective, potentially
      curative open or laparoscopic resection with anastomoses for rectal cancer at the
      Department of Surgery of the University Hospital Ostrava from 1 January 2001 to
      31 December 2009. Anastomotic leakage was defined as clinically or radiologically
      confirmed signs of local or diffuse peritonitis, gas, pus or stool from the
      drain, rectoscopy signs of anastomotic insufficiency, or rectovesical or
      rectovaginal fistula. The Cox proportional hazards model with forward selection
      was used to determine the influence of predefined baseline characteristics on
      overall, disease-free survival and recurrence. The results are presented as
      Hazard Ratio (HR) with 95% Confidence Interval (CI). RESULTS: Based on the Cox
      model, anastomotic leakage was not identified as a factor with a significant
      impact on overall or disease-free survival. Anastomotic leakage, however, has
      remained an independent risk factor for a higher local recurrence rate (Hazard
      Ratio: 6.621, 95% CI 1.289-34.020, p=0.024). On the contrary, anastomotic leakage
      was not identified as a statistically significant prognostic factor for the
      incidence of distant metastases. CONCLUSION: Anastomotic leakage represents an
      independent risk factor for a higher local recurrence rate after curative
      resection for rectal cancer.

PMID- 23965128
TI  - [Examination of lymph nodes in resected colon segments with colorectal
      carcinoma].
AB  - INTRODUCTION: Optimized staging of colorectal carcinoma (CRC) is essential for
      treatment planning and for estimating the prognosis of the disease. In addition
      to tumour size and the depth of bowel wall infiltration, the lymph node status is
      very important for the determination of the disease stage. For this reason,
      detection and assessment of the maximum number of lymph nodes is emphasized in
      the examination of resected segments of the large bowel. The number of lymph
      nodes (LNs) found in the segments resected depends on various circumstances. In
      our study, we focused on factors which could influence the number of pericolic
      LNs. MATERIAL AND METHODS: We examined two groups of CRC patients. The first
      group included 30 patients within the age range of 32-50 years (average: 47.5
      years) and the second group consisted of 90 patients aged between 51 and 87 years
      (average: 68 years). The tumours were localized in various parts of the colon,
      predominantly in the descending colon and the sigmoid colon. Rectal tumour was
      present in 23 patients; 13 of them underwent preoperative chemoradiation therapy
      and 10 of them received no preoperative therapy. The length of the resected colon
      segments (radical intervention) ranged from 6 to 51 cm. The size of CRC ranged
      from 0.5 to 15 cm (average: 4.5 cm). The maximum tumour invasion depth reached
      into the subserosal tissue and pericolic adipose tissue. RESULTS: The number of
      LNs found in 120 resected colon segments ranged from 1 to 60 LNs per case. The
      number of LNs showed differences among the patients and also depended on the
      location of CRC within the large intestine. In the resected segments of the
      ceacum with CRC, the average number of LNs was 11.5, whereas it was only 7 in
      rectal CRC. The largest volume of pericolic adipose tissue was found in the
      caecum, whereas the smallest volume was seen on the rectal circumference. In CRC
      patients aged 50 years or younger, the number of LNs was from 2 to 60 (average:
      17). In contrast, the number of LNs ranged from 1 to 46 (average: 11) in patients
      older than 50 years. In resected segments that were 6 to 12 cm long, the number
      of LNs ranged from 1 to 18 (average: 8). In resected segments that were 12 to 51
      cm long, the number of LNs was from 1 to 60 (average: 13.8). In 13 cases of
      rectal CRC with preoperative chemoradiation therapy, small LNs of an average
      length of 1-3 mm predominated, and the number of LNs ranged between 1 and 13
      (average: 5). The required number of 12 LNs was reached in 4 resected parts of
      the rectum (31%). CONCLUSION: The number of pericolic LNs found in the resected
      segments of the colon and the rectum with CRC depends on various factors. Besides
      individual differences, the number of LNs is influenced by the CRC location in
      the colon, the extent of the resected pericolic adipose tissue, the patients age
      and the length of the segment resected. In cases of rectal CRCs, it is also
      influenced by preoperative chemoradiation therapy.

PMID- 23965129
TI  - [Shoulder arthrodesis using an external fixator in the treatment of chronic
      inflammatory complications of proximal humeral fractures].
AB  - INTRODUCTION: Chronic osteomyelitis is a serious chronic condition that
      frequently results in permanent after-effects. Treatment is complex, lengthy and
      costly. MATERIAL AND METHODS: Between the beginning of 2003 and the end of 2010,
      438 operations of the proximal humerus were performed at our department using
      either angle-stable osteosynthesis or hemiarthroplasty. In four cases out of this
      group of patients, deep tissue infection affecting the bone developed. These four
      patients were treated with arthrodesis of the shoulder joint using an external
      fixation device. Arthrodesis was also the treatment method in a patient who
      previously received conservative treatment but developed chronic osteomyelitis.
      RESULTS: Healing of the infectious focus along with the formation of stable,
      painless shoulder was achieved in all five patients, with the arthrodesis
      offering full support for the limbs periphery. CONCLUSION: The above method
      represents an alternative to reverse arthroplasty of the shoulder joint usually
      performed after infection is cured. While function of the limb usually worsens
      after arthrodesis, the risk of recurring inflammation is substantially lower.

PMID- 23965130
TI  - [Abdominal actinomycosis - 3 case reports and literature overview].
AB  - The authors present three cases of abdominal actinomycosis that were initially
      diagnosed as acute appendicitis, an abscess in the left groin and pelvic tumour,
      probably of gynaecological origin. Definitive diagnosis of abdominal
      actinomycosis was established as late as postoperatively. Abdominal actinomycosis
      is a chronic, infectious disease characterized most frequently by non-specific
      symptoms such as abdominal pain, fever, vomiting, bowel obstruction, weight loss,
      sometimes palpable resistance, and leukocytosis [1-9]. Diagnosis may be difficult
      and needs to be taken into account, especially in patients with risk factors.

PMID- 23965131
TI  - Assessing accuracy of knowledge of cognitive effects of normal ageing and mild
      stage of Alzheimer's disease.
AB  - OBJECTIVES: This study aimed to develop and pilot the Alzheimer's Disease and
      Ageing Perception Scale (ADAPS), examine theory-consistent differences and
      convergent validity, and identify misconceptions of the cognitive effects of
      ageing and mild Alzheimer's disease (AD). METHOD: After piloting a large pool of
      items with a panel of ageing and dementia experts (n = 6), an item analysis
      yielded a 25-item version of the ADAPS (alpha = .70), comprising a Normal Ageing
      subscale (alpha = .68) and Mild AD subscale (alpha = .74). Participants from the
      general community (n = 251) and aged care professionals (n = 59) completed the
      ADAPS, Knowledge of Memory Ageing Questionnaire (KMAQ), and the Alzheimer's
      Disease Knowledge Scale (ADKS). RESULTS: Compared to matched controls, aged care
      professionals demonstrated greater accuracy of knowledge on the Mild AD subscale
      (p < .05), but not the Normal Ageing subscale (p > .05) of the ADAPS. The pattern
      of significant correlations between the ADAPS, KMAQ, and ADKS supported the
      convergent validity of the ADAPS. The most common misconceptions on the ADAPS
      indicated a tendency for participants to overgeneralise the cognitive effects of
      normal ageing. CONCLUSION: This preliminary study introduces a new tool for
      assessing accuracy of knowledge of cognitive effects associated with normal
      ageing and mild AD, and may assist in identifying misconceptions of the ageing
      process.

PMID- 23965132
TI  - Draft genome sequences of two super-extensively  drug-resistant isolates of
      Mycobacterium tuberculosis  from China.
AB  - The prevalence of drug-resistance in Mycobacterium tuberculosis is already having
      a negative impact on the control of tuberculosis. We report the draft genome
      sequences of two super-extensively drug-resistant M. tuberculosis isolates from
      China, FJ05194 (lineage 2) and GuangZ0019 (lineage 4), and compare them with the
      H37Rv reference strain to identify possible sources of genetic variation
      associated with their extensive drug resistance. Our results suggest that their
      extensive drug resistance probably results from the stepwise accumulation of
      resistances to individual drugs.

PMID- 23965133
TI  - Fc-gamma receptor polymorphisms as predictive and prognostic factors in patients
      receiving oncolytic adenovirus treatment.
AB  - BACKGROUND: Oncolytic viruses have shown potential as cancer therapeutics, but
      not all patients seem to benefit from therapy. Polymorphisms in Fc gamma
      receptors (FcgRs) lead to altered binding affinity of IgG between the receptor
      allotypes and therefore contribute to differences in immune defense mechanisms.
      Associations have been identified between FcgR polymorphisms and responsiveness
      to different immunotherapies. Taken together with the increasing understanding
      that immunological factors might determine the efficacy of oncolytic virotherapy
      we studied whether FcgR polymorphisms would have prognostic and/or predictive
      significance in the context of oncolytic adenovirus treatments. METHODS: 235
      patients with advanced solid tumors were genotyped for two FcgR polymorphisms,
      FcgRIIa-H131R (rs1801274) and FcgRIIIa-V158F (rs396991), using TaqMan based qPCR.
      The genotypes were correlated with patient survival and tumor imaging data.
      RESULTS: In patients treated with oncolytic adenoviruses, overall survival was
      significantly shorter if the patient had an FcgRIIIa-VV/ FcgRIIa-HR (VVHR)
      genotype combination (P = 0,032). In contrast, patients with FFHR and FFRR
      genotypes had significantly longer overall survival (P = 0,004 and P = 0,006,
      respectively) if they were treated with GM-CSF-armed adenovirus in comparison to
      other viruses. Treatment of these patients with unarmed virus correlated with
      shorter survival (P < 0,0005 and P = 0,016, respectively). Treating FFHH
      individuals with CD40L-armed virus resulted in longer survival than treatment
      with other viruses (P = 0,047). CONCLUSIONS: Our data are compatible with the
      hypothesis that individual differences in effector cell functions, such as NK
      cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and tumor antigen
      presentation by APCs caused by polymorphisms in FcgRs could play role in the
      effectiveness of oncolytic virotherapies. If confirmed in larger populations,
      FcgR polymorphisms could have potential as prognostic and predictive biomarkers
      for oncolytic adenovirus therapies to enable better selection of patients for
      clinical trials. Also, putative associations between genotypes, different viruses
      and survival implicate potentially important mechanistic issues.

PMID- 23965135
TI  - Direct visualization of "coagulative nucleation" in surfactant-free emulsion
      polymerization.
AB  - It is generally believed that surfactant-free emulsion polymerization involves
      four steps: initiation, nucleation into primary particles, coagulation into
      secondary particles, and growth. By high resolution SEM-imaging of the
      intermediate polymerization products, the evolution of the morphology of the
      polymer particles has been followed. This allowed us, to our best knowledge for
      the first time, to visualize "coagulative nucleation", which is the process where
      the primary nanoparticles aggregate into larger entities. The obtained visual
      information and data on particle size, number, and zeta potential, strongly
      suggest that coagulative termination is responsible for the coagulative
      nucleation phenomenon, resulting in a dispersion of fine, relatively uniform
      polymer particles. 

PMID- 23965134
TI  - Hyperphosphatemia is associated with anemia in adults without chronic kidney
      disease: results from the National Health and Nutrition Examination Survey
      (NHANES): 2005-2010.
AB  - BACKGROUND: Hyperphosphatemia, serum phosphorus >= 4.4 mg/dL, is associated with
      increased risk for chronic kidney disease and cardiovascular disease. Previous
      studies have shown a weak association between dietary phosphorus intake and serum
      phosphorus concentrations. While much less common in the general population,
      hypophosphatemia (< 2.5 mg/dL) may be associated with metabolic syndrome and
      obesity. METHODS: Using three cycles from the National Health and Nutrition
      Examination Survey (NHANES) (2005-2010), this study evaluated independent risk
      factors for hyperphosphatemia and hypophosphatemia. RESULTS: Risk factors for
      hyperphosphatemia included higher adjusted calcium (OR 2.90, 95% CI 2.43-3.45),
      increasing cholesterol (OR 1.003, 95% CI 1.001-1.005), female gender (OR 1.61,
      95% CI 1.39-1.87) and low hemoglobin (OR 1.52, 95% CI 1.17-1.98). Advanced age
      was protective (OR 0.98, 95% CI 0.977-0.987). Models that included fasting serum
      glucose found lower body mass index (BMI) to be protective (OR 0.97, 95% CI 0.96
      0.99) and adjusting for serum vitamin D and parathyroid hormone removed the
      association with low hemoglobin and BMI. Risk factors for hypophosphatemia
      included the following protective factors: higher albumin (OR 0.56, 95% CI 0.35
      0.93), higher BUN (OR 0.90, 95% CI 0.86, 0.95), corrected calcium (OR 0.38, 95%
      CI 0.23-0.63) and female gender (OR 0.47, 95% 0.24-0.94). In men, higher fasting
      glucose levels increased risk (OR 1.01, 95% CI 1.0004-1.01). CONCLUSION: This
      study is the first to show an association between low hemoglobin levels and
      increased risk for hyperphosphatemia among individuals without chronic kidney
      disease. We did not find any association between diabetes mellitus, increasing
      BMI or fasting glucose levels and hypophosphatemia.

PMID- 23965137
TI  - Scaling estimates of amplitude for movements without visual guidance.
AB  - Three groups of subjects were involved in estimating movement amplitudes. Two of
      these groups used the method of estimation, labeling the amplitudes of simple
      linear movements in inches. One group made active movements, the other
      experienced passive movement of the arm. The third group, using the method of
      production, attempted to move the distance required by the experimenter's label.
      Performance was described in terms of absolute, algebraic, and intrasubject
      variable error. No striking differences were noted between the three task groups,
      but males and females differed systematically. Females tended to over-estimate
      and males to underestimate the distances moved. Lack of evidence for any range
      effect suggests that subjects were operating from relatively stable perceptual
      traces, accessed by the verbal labels, rather than from memory traces of previous
      estimates of the same amplitudes. 

PMID- 23965136
TI  - Examining the impact of larval source management and insecticide-treated nets
      using a spatial agent-based model of Anopheles gambiae and a landscape generator
      tool.
AB  - BACKGROUND: Agent-based models (ABMs) have been used to estimate the effects of
      malaria-control interventions. Early studies have shown the efficacy of larval
      source management (LSM) and insecticide-treated nets (ITNs) as vector-control
      interventions, applied both in isolation and in combination. However, the
      robustness of results can be affected by several important modelling assumptions,
      including the type of boundary used for landscapes, and the number of replicated
      simulation runs reported in results. Selection of the ITN coverage definition may
      also affect the predictive findings. Hence, by replication, independent
      verification of prior findings of published models bears special importance.
      METHODS: A spatially-explicit entomological ABM of Anopheles gambiae is used to
      simulate the resource-seeking process of mosquitoes in grid-based landscapes. To
      explore LSM and replicate results of an earlier LSM study, the original
      landscapes and scenarios are replicated by using a landscape generator tool, and
      1,800 replicated simulations are run using absorbing and non-absorbing
      boundaries. To explore ITNs and evaluate the relative impacts of the different
      ITN coverage schemes, the settings of an earlier ITN study are replicated, the
      coverage schemes are defined and simulated, and 9,000 replicated simulations for
      three ITN parameters (coverage, repellence and mortality) are run. To evaluate
      LSM and ITNs in combination, landscapes with varying densities of houses and
      human populations are generated, and 12,000 simulations are run. RESULTS: General
      agreement with an earlier LSM study is observed when an absorbing boundary is
      used. However, using a non-absorbing boundary produces significantly different
      results, which may be attributed to the unrealistic killing effect of an
      absorbing boundary. Abundance cannot be completely suppressed by removing aquatic
      habitats within 300 m of houses. Also, with density-dependent oviposition,
      removal of insufficient number of aquatic habitats may prove counter-productive.
      The importance of performing large number of simulation runs is also
      demonstrated. For ITNs, the choice of coverage scheme has important implications,
      and too high repellence yields detrimental effects. When LSM and ITNs are applied
      in combination, ITNs' mortality can play more important roles with higher
      densities of houses. With partial mortality, increasing ITN coverage is more
      effective than increasing LSM coverage, and integrating both interventions yields
      more synergy as the densities of houses increase. CONCLUSIONS: Using a non
      absorbing boundary and reporting average results from sufficiently large number
      of simulation runs are strongly recommended for malaria ABMs. Several guidelines
      (code and data sharing, relevant documentation, and standardized models) for
      future modellers are also recommended.

PMID- 23965138
TI  - Temporal distribution of attention during a throwing motion.
AB  - A reaction-time measure of attention was employed during five segments of a
      simultaneous dart throw: premovement decision, immediately after recoil was
      begun, maximum recoil, immediately after forward movement was begun, and after
      release of the dart. Reaction time was significantly longer when the stimulus was
      presented during the first or second segment than during later segments. Reaction
      time during premovement was not consistently greater than that immediately after
      movement was begun, indicating that information is being sampled at a high rate
      after movement commences. It appears that monitoring of proprioceptive feedback
      after movement has begun, and initiation of corrective submovements, is necessary
      for skillful performance of dart throwing. 

PMID- 23965139
TI  - Individual differences in motor skill acquisition.
AB  - Jones' (1972) theory relative to the superdiagonal form of a correlation matrix
      of repeated trials for a psychomotor task was evaluated for three tasks: pursuit
      rotor, stabilometer, and Rhythmic Analysis System. Results indicated no support
      for Jones' statement that most complex psychomotor skills show increasing
      superdiagonal form. In fact only limited support was found for any type
      superdiagonal form. However, 8 to 10 trials did appear to be necessary for
      agreement between the dependent variables for both the pursuit rotor and
      stabilometer. In addition, a plateau in the acquisition curve for these two tasks
      on the time-dependent variable appeared after 8 to 10 trials. 

PMID- 23965140
TI  - Preview and movement as determiners of timing a discrete motor response.
AB  - Preview and voluntary movement in discrete motor response timing was
      investigated. Subjects lifted the right index finger from a response key when a
      moving pointer (1.260-sec travel time) passed directly under a stationary
      pointer. Four groups of 15 male and female college students performed 150 trials
      of the timing task with knowledge of results after each trial under one of four
      conditions: (a) preview of the moving pointer and left-arm movement, (b) preview
      of the moving pointer but no left-arm movement, (c) left-arm movement but no
      preview, and (d) no preview and no left-arm movement. Preview led to greater
      timing accuracy and consistency than did either no preview or movement. Movement
      did not influence timing accuracy, but resulted in greater timing consistency in
      the absence of preview. When preview and movement were available at the same
      time, the subject relied on preview to keep time. 

PMID- 23965141
TI  - An investigation of fitts' law using a wide range of movement amplitudes.
AB  - The relationship between Fitts' Index of Difficulty (ID = log2 2A/W) and movement
      time was investigated for finger, wrist, and whole arm motions over a wide range
      of movement distances (0.25 to 30.5 cm). Results supported Fitts' original
      speculation that various limb segments may show different maximum information
      processing rates. Short-distance finger and wrist motions showed much higher
      rates (38 and 23 bits/sec, respectively) than longer-distance arm motions (10
      bits/sec). Examination of motion trajectories qualitatively supported a
      descriptive model whereby a visually mediated discrete-correction control process
      is used, as proposed by Crossman and Goodeve (Note 1) and Keele (1968). However,
      evidence of severe nonlinearities in the measured human movement responses did
      not support the use of linear control models in explaining the empirical validity
      of Fitts' law in predicting human motor performance. 

PMID- 23965142
TI  - A note on delay of knowledge of results in positioning responses.
AB  - Earlier studies of knowledge of results delay in positioning responses have
      required subjects to move "briskly" to the target position, creating a potential
      bias in the interpretation of the results for recall and recognition memory
      mechanisms. The present experiment varied delay (2 or 30 sec) in two groups of 20
      females. Subjects were instructed to move very slowly and the starting positions
      were varied to prevent pre-programmed movements of a given extent. Even with
      these methodological changes, there was no evidence that the delay variable was
      relevant for learning in positioning responses. 

PMID- 23965143
TI  - Memory and perceptual trace development in ballistic timing.
AB  - Adams' (1971) closed-loop theory holds that memory and perceptual trace
      development is a function of the amount of practice with knowledge of results. If
      knowledge of results is withdrawn before these two memory states are strong
      performance will worsen, but after substantial practice performance can be
      maintained and evaluated in the absence of knowledge of results. To test the
      first prediction, three independent groups were given varying amounts of KR
      trials prior to early knowledge of results withdrawal. Subjects attempted to
      produce a 24.13-cm movement in exactly 150 msec. Memory and perceptual trace
      performance (as reflected in mean absolute and mean absolute estimated error,
      respectively) were dependent on the amount of knowledge of results practice, and
      the memory and perceptual trace remained reasonably strong during late knowledge
      of results withdrawal. 

PMID- 23965144
TI  - More on absolute error, etc.
AB  - It is argued on statistical and conceptual grounds that absolute error can be a
      meaningful measure of performance. When approximately half of each group performs
      consistently on either side of the criterion, groups can have equal algebraic
      error and variable error means, leaving absolute error as the only dependent
      variable to discriminate between the groups. Additionally, absolute error is
      invariably the dependent variable subjects are asked to minimize in the
      experimental situation. If researchers persist in measuring motor performance
      through error scores, judicious use of absolute error is appropriate. Requests
      for reprints should be sent to K.M. Newell, Institute for Child Behavior and
      Development, University of Illinois, Champaign, IL 61820. 

PMID- 23965145
TI  - The effect of practice on human performance in a preview-constrained motor
      control task.
AB  - This study examined the effect of short-term practice on the parameters of a
      linear model involving mean arm movement time as a function of Fitts's index of
      difficulty (ID) variable and a preview-constraint ID variable. Significant (at
      the 2% level) interactions were found to exist between practice and the two ID
      variables indicating that the model parameters associated with these variables
      are both linear functions of practice time. 

PMID- 23965146
TI  - The nerve compression block technique.
AB  - In a study by Kelso, Stelmach, and Wanamaker (1974), data were presented showing
      a progressive decrement in electromyographic responses to supramaximal whole
      nerve stimulation with the development of ischemia-induced anoxia. Accordingly,
      they questioned the suitability of employing ischemia-induced anesthesia (nerve
      compression block) in the study of movement control. In the present paper issues
      relating to the review of existing literature, the methodology employed and the
      conclusions reached in the Kelso et al. study are discussed. 

PMID- 23965147
TI  - The continuing saga of the nerve compression block technique.
AB  - In response to Bairstow and Laszlo (1976) the present paper points out the
      inconsistencies of their arguments relative to Laszlo's previous work and that of
      Kelso, Stelmach, and Wanamaker (1974). Data are presented indicating that the
      nerve compression block, as a tool, fails to meet the stringent requirements
      necessary for examining motor performance in the absence of kinesthetic
      information. Some possibilities for the discrepancy between Laszlo's performance
      data and those from Kelso et al. are discussed. These hinge on the availability
      of sensory information rather than any artifact in the Kelso et al. nerve
      conduction procedures as Bairstow and Laszlo (1976) suggest. 

PMID- 23965148
TI  - Reasons to be hopeful.

PMID- 23965149
TI  - High throughput detection of human neutrophil peptides from serum, saliva, and
      tear by anthrax lethal factor-modified nanoparticles.
AB  - Human alpha defensins human neutrophil peptide 1-3 (HNP 1-3) are potential
      prognostic cancer biomarkers. Metalloprotein anthrax lethal factor (ALF) binds to
      HNP 1-3 in a Zn2+-dependent manner. We conjugated ALF to the surface of magnetic
      nanoparticles (MNP) to magnetically isolate the HNPs, and used Zn2+ to control
      the capture and release HNPs.

PMID- 23965151
TI  - Ag+-mediated DNA base pairing: extraordinarily stable pyrrolo-dC-pyrrolo-dC pairs
      binding two silver ions.
AB  - 6-Substituted pyrrolo-dC-pyrrolo-dC mismatches selectively capture silver ions to
      form extraordinarily stable metal-mediated base pairs. One single modification in
      a 12-mer duplex causes a Tm increase of 36.0  degrees C relative to the metal
      free mismatched duplex. Spectrophotometric titrations as well as ESI mass spectra
      confirmed the binding of two silver ions per base pair. The Ag(+)-mediated base
      pairs may permit the construction of metal-responsive DNA with a very high silver
      loading. 

PMID- 23965150
TI  - Obstetric fistula in Burundi: a comprehensive approach to managing women with
      this neglected disease.
AB  - BACKGROUND: In Burundi, the annual incidence of obstetric fistula is estimated to
      be 0.2-0.5% of all deliveries, with 1000-2000 new cases per year. Despite this
      relatively high incidence, national capacity for identifying and managing
      obstetric fistula is very limited. Thus, in July 2010, Medecins Sans Frontieres
      (MSF) set up a specialised Obstetric Fistula Centre in Gitega (Gitega Fistula
      Centre, GFC), the only permanent referral centre for obstetric fistula in
      Burundi. A comprehensive model of care is offered including psychosocial support,
      conservative and surgical management, post-operative care and follow-up. We
      describe this model of care, patient outcomes and the operational challenges.
      METHODS: Descriptive study using routine programme data. RESULTS: Between July
      2010 and December 2011, 470 women with obstetric fistula presented for the first
      time at GFC, of whom 458 (98%) received treatment. Early urinary catheterization
      (conservative management) was successful in four out of 35 (11%) women. Of 454
      (99%) women requiring surgical management, 394 (87%) were discharged with a
      closed fistula, of whom 301 (76%) were continent of urine and/or faeces, while 93
      (24%) remained incontinent of urine and/or faeces. In 59 (13%) cases, the fistula
      was complex and could not be closed. Outcome status was unknown for one woman.
      Median duration of stay at GFC was 39 days (Interquartile range IQR, 31-51 days).
      CONCLUSION: In a rural African setting, it is feasible to implement a
      comprehensive package of fistula care using a dedicated fistula facility, and
      satisfactory surgical repair outcomes can be achieved. Several operational
      challenges are discussed.

PMID- 23965152
TI  - Melioidosis presenting as pseudomyxoma peritonei: yet another pretense of the
      great mimicker: an unreported entity.
AB  - BACKGROUND: Melioidosis, a lethal infectious disease caused by Burkholderia
      pseudomallei, an important human pathogen in tropical regions, is notorious for
      its diverse clinical presentations. METHODS: We report a case of a 55-year-old
      woman with a history of total abdominal hysterectomy with bilateral salpingo
      oophorectomy for ovarian mucinous cystadenocarcinoma five years back, who
      presented with complaints of chest pain, abdominal distention, and breathlessness
      for one week. Ultrasound-guided aspiration of the peritoneal free fluid revealed
      a thick gelatinous material consistent with pseudomyxoma peritonei. Cytologic
      analysis of the aspirate was negative for malignant cells, but bacterial culture
      proved positive for Burkholderia pseudomallei. RESULTS: She was started on
      ceftazidime, and she improved symptomatically and was discharged on oral
      doxycycline and chloramphenicol after three weeks of intravenous antibiotic
      therapy. CONCLUSION: This case is being reported to emphasize an unusual
      presentation of melioidosis and the significance of timely appropriate antibiotic
      therapy.

PMID- 23965153
TI  - Reply to Silvestri et al.

PMID- 23965154
TI  - Susceptibility to stress induced visceral hypersensitivity in maternally
      separated rats is transferred across generations.
AB  - BACKGROUND: In irritable bowel syndrome (IBS), familial clustering and transfer
      across generations may largely depend on environmental factors but this is
      difficult to establish in the human setting. Therefore, we aimed to set up a
      relevant animal model. We investigated whether susceptibility to stress induced
      visceral hypersensitivity in maternally separated (MS) Long Evans rats can be
      transferred across generations without further separation protocols and, if so,
      whether this depends on maternal care. METHODS: At adult age, we evaluated pre-
      vs post water avoidance (WA) changes in visceromotor response to distension in
      non-handled second filial generation offspring (NH-F2) of previously separated MS
      F1 dams. Furthermore, the role of maternal care was evaluated by cross-fostering
      F2 offspring of NH-F1 and MS-F1 dams and subsequent sensitivity measurements at
      adult age. Involvement of mast cells in post stress hypersensitivity of NH-F2
      rats was evaluated by mast cell stabilization. KEY RESULTS: In adult NH-F2
      offspring of MS-F1 dams, post-WA hypersensitivity to colorectal distension was
      observed in 80% of rats compared with 19% in offspring of NH-F1 dams. Cross
      fostered pups adapted to the phenotype of the foster mother: pups of NH-F1 dams
      nursed by MS-F1 dams showed post-WA hypersensitivity to distension at adult age
      and vice versa (100% and 20% respectively). In NH-F2 rats, post-WA
      hypersensitivity was reversed by mast cell stabilizer doxantrazole. CONCLUSIONS &
      INFERENCES: Maternal separated-induced susceptibility to stress-triggered
      visceral hypersensitivity is transferred across generations and this transfer
      depends on maternal care. Thus, MS is a suitable model to evaluate environmental
      triggers relevant to IBS clustering in families.

PMID- 23965155
TI  - Molecular epidemiological study of clinical Acinetobacter baumannii isolates:
      phenotype switching of antibiotic resistance.
AB  - BACKGROUND: The presence of clinical Acinetobacter baumannii (A. baumannii)
      isolates with differing antibiotic resistance phenotypes in the same patient
      causes difficulties and confusion in treatment. This phenomenon may be caused by
      reasons such as cross-infection from neighboring patients that switches to
      different A. baumannii strain, natural mutation of A. baumannii, inducing of
      different antibiotic resistance genes expression or acquisition of genes
      conferring resistance from another source. To elucidate this question, clinical
      A. baumannii strains, isolated from the same individual patients, showed
      antibiotic resistance phenotypes switching during the same hospitalization
      period, were attentively collected for further analysis. Molecular approaches for
      phylogenetic analysis, including pulsed field gel electrophoresis, multilocus
      sequence typing, and short tandem repeat analysis, were employed for the
      chronological studies. FINDINGS: Our results showed that antibiotic resistance
      phenotype switching could have occurred as a result through both cross-infection
      and natural mutation roots. Our results also suggest that rapid phenotype
      switching between paired isolates could occur during one single course of
      antibiotic treatment. CONCLUSIONS: Though cross infection caused antibiotic
      resistance phenotype switching does occur, natural mutation of A. baumannii
      isolates is particularly cautious for antibiotic treatment.

PMID- 23965156
TI  - From the Flavobacterium genus to the phylum Bacteroidetes: genomic analysis of
      dnd gene clusters.
AB  - Phosphorothioate modification of DNA and the corresponding DNA degradation (Dnd)
      phenotype that occurs during gel electrophoresis are caused by dnd genes.
      Although widely distributed among Bacteria and Archaea, dnd genes have been found
      in only very few, taxonomically unrelated, bacterial species so far. Here, we
      report the presence of dnd genes and their associated Dnd phenotype in two
      Flavobacterium species. Comparison with dnd gene clusters previously described
      led us to report a noncanonical genetic organization and to identify a gene
      likely encoding a hybrid DndE protein. Hence, we showed that dnd genes are also
      present in members of the family Flavobacteriaceae, a bacterial group occurring
      in a variety of habitats with an interesting diversity of lifestyle. Two main
      types of genomic organization of dnd loci were uncovered probably denoting their
      spreading in the phylum Bacteroidetes via distinct genetic transfer events. 

PMID- 23965157
TI  - Indium-based ultraviolet-transparent electroconductive oxyfluoride InOF: ambient
      pressure synthesis and unique electronic properties in comparison with In2O3.
AB  - A method for the synthesis of single-phase powdered InOF under ambient pressure
      has been developed. The method involves pyrolysis of a hydrate of InF3 in an O2
      atmosphere of controlled humidity. Various intermediate phases were formed during
      the pyrolysis, and their structures and interconversions were analyzed. Combined
      results of optical absorption measurements and density functional calculations
      indicate that InOF is a direct band gap material with a band gap energy of ~3.7
      eV. Unlike In2O3, the electrical conductivity of polycrystalline InOF pellets can
      be controlled over ~8 orders of magnitude from ~10(-8) S cm(-1) to ~2 S cm(-1) by
      thermal annealing, and the sample with the highest conductivity was a nearly
      degenerate n-type semiconductor with a relatively small carrier concentration of
      ~10(18) cm(-3). The work function of InOF measured by ultraviolet photoelectron
      spectroscopy is ~3.5 eV and is smaller by ~1.5 eV than that of In2O3. This
      difference comes from a decrease in the electron affinity. 

PMID- 23965158
TI  - Modulation of cardiometabolic pathways in skin and serum from patients with
      psoriasis.
AB  - BACKGROUND: Moderate-to-severe psoriasis is associated with an increased risk of
      atherosclerotic cardiovascular disease (ASCVD); however, the link is poorly
      understood. METHODS: Skin and serum from patients with psoriasis were evaluated
      to understand if there was evidence of dysregulation in a targeted group of
      inflammatory and lipid genes related to ASCVD. Microarray analyses of expression
      of targeted ASCVD genes from skin in 89 patients with moderate-to-severe
      psoriasis from the ACCEPT trial were compared with non-diseased skin from healthy
      controls (n = 25). Serum (n = 149) was tested at baseline for monocyte
      chemoattractant protein-1 (MCP-1), macrophage-derived chemokine (MDC), and
      apolipoprotein-A1 (Apo-A1) comparing to healthy controls (n=162). RESULTS: An
      increase in skin gene expression for MCP-1 (7.98-fold) and MDC (6.66-fold) (p <
      0.001 each) was observed in lesional versus healthy skin. Significant decreases
      in liver X receptor-alpha (LXR-alpha) (-5.94-fold), a protective lipoprotein
      metabolism gene, and in peroxisome proliferator-activated receptor-alpha (PPAR
      alpha) (-7.58-fold), a protective anti-inflammatory and lipid modulating gene,
      were observed in lesional versus healthy skin (p < 0.001 each). Serum analyses
      revealed that MCP-1 (502 vs. 141 pg/mL) and MDC (1240 vs. 409 pg/mL) levels were
      significantly elevated in psoriasis compared with healthy controls (p < 0.001
      each). Dysregulated lipid metabolism was also evident in the serum, as Apo-A1, a
      protein product related to PPAR-alpha activation, was significantly decreased in
      patients with psoriasis compared with healthy controls (25.2 vs. 38.9 mg/dL; p <
      0.001). CONCLUSIONS: Analyses of targeted genes and their products known to be
      associated with ASCVD revealed dysregulation of inflammatory (MCP-1 and MDC) and
      lipid metabolism (LXR-alpha, PPAR-alpha) genes in psoriasis. These findings
      provide evidence of a potential shared pathophysiology linking psoriasis to
      cardiometabolic diseases.

PMID- 23965159
TI  - Regional variation in distal esophagus distensibility assessed using the
      functional luminal imaging probe (FLIP).
AB  - BACKGROUND: This study aimed to evaluate the spatial variation in esophageal
      distensibility in normal subjects using a novel multichannel functional luminal
      imaging probe (FLIP). METHODS: Ten healthy subjects (four men, age 21-49 years)
      were evaluated during endoscopy with a high-resolution impedance planimetry probe
      (FLIP) positioned through the esophagogastric junction (EGJ) and distal 10 cm of
      the esophageal body. Stepwise bag distensions using 5-mL increments from 0 to 60
      mL were conducted, and simultaneous measurements of cross-sectional area (CSA)
      and the associated intrabag pressure from each subject were analyzed using a
      customized MATLABTM program. The distensibility along the esophagus was
      determined and compared between the EGJ and interval locations at 2-5 cm and 6-10
      cm above the EGJ. KEY RESULTS: The pressure-CSA relationship was nearly linear
      among sites at lower pressures (0 to 7.5 mmHg) and reached a distension plateau
      at pressures ranging from 8 to 24 mmHg. The location of greatest distensibility
      was 4 cm above the EGJ. Although the CSAs of individual recording loci were not
      significantly different, there was a significant difference between the mean CSAs
      when comparing the region 2 to 5 cm proximal to EGJ with that 6 to 10 cm proximal
      to the EGJ. CONCLUSIONS & INFERENCES: There were significant regional differences
      in distensibility along the distal esophagus with lower values in the proximal
      part compared with more distal part. The greatest distensibility was noted to
      occur at about 4 cm above the EGJ in close proximity to the location of the
      contractile deceleration point and phrenic ampulla.

PMID- 23965162
TI  - How much to worry about the FDA warning in the use of citalopram?
AB  - A number of studies have suggested that antidepressants such as selective
      serotonin reuptake inhibitors may increase a risk of developing harmful cardiac
      adverse event such as QT interval prolongation. In fact, the US Food and Drug
      Administration (FDA) consecutively gave safety warnings to healthcare
      professionals that the use of citalopram may be associated with QT interval
      prolongation in 2011 and 2012. Despite the fact that citalopram has been one of
      the most acceptable antidepressants worldwide, concerns on citalopram about
      cardiac safety issues have become apparent to clinicians after the FDA warning.
      However, a recent cohort study raises some practical questions about the FDA
      warnings on the use of citalopram and may also provide clinicians with a good
      guidance for prudent use of citalopram in clinical practice.

PMID- 23965160
TI  - A multiple-alignment based primer design algorithm for genetically highly
      variable DNA targets.
AB  - BACKGROUND: Primer design for highly variable DNA sequences is difficult, and
      experimental success requires attention to many interacting constraints. The
      advent of next-generation sequencing methods allows the investigation of rare
      variants otherwise hidden deep in large populations, but requires attention to
      population diversity and primer localization in relatively conserved regions, in
      addition to recognized constraints typically considered in primer design.
      RESULTS: Design constraints include degenerate sites to maximize population
      coverage, matching of melting temperatures, optimizing de novo sequence length,
      finding optimal bio-barcodes to allow efficient downstream analyses, and
      minimizing risk of dimerization. To facilitate primer design addressing these and
      other constraints, we created a novel computer program (PrimerDesign) that
      automates this complex procedure. We show its powers and limitations and give
      examples of successful designs for the analysis of HIV-1 populations.
      CONCLUSIONS: PrimerDesign is useful for researchers who want to design DNA
      primers and probes for analyzing highly variable DNA populations. It can be used
      to design primers for PCR, RT-PCR, Sanger sequencing, next-generation sequencing,
      and other experimental protocols targeting highly variable DNA samples.

PMID- 23965163
TI  - Acute ischemic stroke: comparison of low-dose and standard-dose regimes of tissue
      plasminogen activator.
AB  - Intravenous tissue plasminogen activator (IV-TPA), administered within 4.5 h of
      symptom onset, is the only therapeutic agent approved for achieving arterial
      recanalization in acute ischemic stroke. Current major guidelines recommend the
      use of a standard dose (0.9 mg/kg bodyweight; maximum 90 mg) of IV-TPA. However,
      comparable efficacy of IV-TPA was demonstrated in the observational studies from
      Japan when a lower dose (0.6 mg/kg bodyweight; maximum 60 mg) was used and later
      approved by the regulatory authorities. Although limited in numbers, considerable
      variations in the dose of IV-TPA are noted in recent publications from Asia, with
      variable results and optimal dose of TPA in Asia remains controversial. The
      authors present a systemic review of the existing literature and compare the
      efficacy and safety of standard-versus the low-dose IV-TPA therapy in acute
      ischemic stroke. 

PMID- 23965164
TI  - Pharmacological therapies to enhance motor recovery and walking after stroke:
      emerging strategies.
AB  - Stroke is the most common serious neurological disorder. To date, the focus for
      research and trials has been on prevention and acute care. Many patients are left
      with serious neurological impairments and limitations in activity and
      participation after stroke. Recent preliminary research and trials suggest that
      the brain is 'plastic' and that the natural history of stroke recovery can be
      improved by physical therapy and pharmacotherapy. Motor weakness and the ability
      to walk have been the primary targets for testing interventions that may improve
      recovery after stroke. Physical therapeutic interventions enhance recovery after
      stroke; however, the timing, duration and type of intervention require
      clarification and further trials. Pharmacotherapy, in particular with
      dopaminergic and selective serotonin-reuptake inhibitors, shows promise in
      enhancing motor recovery after stroke; however, further large-scale trials are
      required. 

PMID- 23965165
TI  - Management of blood pressure in acute stroke.
AB  - The importance of elevated or low arterial blood pressure (BP) early after
      stroke, and the need for pharmacological intervention to control BP, remains
      controversial. Debate surrounds if, when and how to intervene. This debate is
      informed by conflicting results from observational data and underpowered clinical
      trials and substantive outcome data are lacking. Accordingly, management
      decisions have largely been left up to the individual treating physician and
      guidelines are based on 'good practice' and theory rather than level 1, grade A
      evidence. Substantial progress has been made in recent years, particularly in the
      field of hemorrhagic stroke, where recently presented and soon to completed large
      scale trials may finally give us a firm evidence base. For ischemic stroke, many
      important studies have informed our understanding of the basic pathophysiology,
      epidemiology, treatment and outcomes of BP management in acute stroke and,
      although not yet constituting a solid 'evidence base', are helping us from the
      'cognitive quick-sand' of small studies and personal experiences. 

PMID- 23965166
TI  - Acetyl-L-carnitine: from a biological curiosity to a drug for the peripheral
      nervous system and beyond.
AB  - Acetyl-L-carnitine (ALC) is a molecule derived from acetylation of carnitine in
      the mitochondria. Carnitine acetylation enables the function of CoA and
      facilitates elimination of oxidative products. Beyond this metabolic activity,
      ALC provides acetyl groups for acetylcholine synthesis, exerts a cholinergic
      effect and optimizes the balance of energy processes. Acetylcarnitine
      supplementation induces neuroprotective, neurotrophic and analgesic effects in
      the peripheral nervous system. In the recent studies, ALC, by acting as a donor
      of acetyl groups to NF-kb p65/RelA, enhanced the transcription of the GRM2 gene
      encoding the mGLU2 receptors, inducing long-term upregulation of the mGluR2,
      evidencing therefore that its long-term analgesic effects are dependent on
      epigenetic modifications. Several studies, including double-blind, placebo
      controlled, parallel group studies and few open studies showed the effect of ALC
      in diseases characterized by neuropathies and neuropathic pain: the studies
      included diabetic neuropathy, HIV and antiretroviral therapy-induced
      neuropathies, neuropathies due to compression and chemotherapeutic agents. Double
      blinded studies involved 1773 patients. Statistical evaluations evidenced
      reduction of pain, improvements of nerve function and trophism. In conclusion,
      ALC represents a consistent therapeutic option for peripheral neuropathies, and
      its complex effects, neurotrophic and analgesic, based on epigenetic mechanism,
      open new pathways in the study of peripheral nerve disease management. 

PMID- 23965167
TI  - Self-catalytic crystal growth, formation mechanism, and optical properties of
      indium tin oxide nanostructures.
AB  - In-Sn-O nanostructures with rectangular cross-sectional rod-like, sword-like, and
      bowling pin-like morphologies were successfully synthesized through self
      catalytic growth. Mixed metallic In and Sn powders were used as source materials,
      and no catalyst layer was pre-coated on the substrates. The distance between the
      substrate and the source materials affected the size of the Sn-rich alloy
      particles during crystal growth in a quartz tube. This caused In-Sn-O
      nanostructures with various morphologies to form. An X-ray photoelectron
      spectroscope and a transmittance electron microscope with an energy-dispersive X
      ray spectrometer were used to investigate the elemental binding states and
      compositions of the as-synthesized nanostructures. The Sn doping and oxygen
      vacancies in the In2O3 crystals corresponded to the blue-green and yellow-orange
      emission bands of the nanostructures, respectively. 

PMID- 23965168
TI  - Spin-enabled plasmonic metasurfaces for manipulating orbital angular momentum of
      light.
AB  - Here, we investigate the spin-induced manipulation of orbitals using metasurfaces
      constructed from geometric phase elements. By carrying the spin effects to the
      orbital angular momentum, we show experimentally the transverse angular splitting
      between the two spins in the reciprocal space with metasurface, as a direct
      observation of the optical spin Hall effect, and an associated global orbital
      rotation through the effective orientations of the geometric phase elements. Such
      spin-orbit interaction from a metasurface with a definite topological charge can
      be geometrically interpreted using the recently developed high order Poincare
      sphere picture. These investigations may give rise to an extra degree of freedom
      in manipulating optical vortex beams and orbitals using "spin-enabled"
      metasurfaces. 

PMID- 23965169
TI  - Dried blood spot sampling for detection of monoclonal immunoglobulin gene
      rearrangement.
AB  - Molecular methods are important tools for diagnosis and monitoring of many
      lymphoproliferative disorders. The reliability of lymphoma diagnoses is
      strikingly different between developed and developing countries, partly due to
      lack of access to these advanced molecular analyses. To overcome these problems,
      we propose a new application of dried blood spots (DBS) for detecting clonal B
      cell populations in peripheral blood (PB). We ensured that the DBS contained
      sufficient lymphocytes to perform a PCR-based clonality assay without producing
      false positives. Using the Namalwa B-cell line, we established that the assay is
      sensitive enough to detect 200 clonal cells in the analyzed sample. Very similar
      clonal results were obtained between DNA from DBS and fresh whole blood from
      patients with B-cell chronic lymphocytic leukemia. B-cell clonality can also be
      detected in DBS from African children with EBV-associated diseases. This is the
      first study demonstrating that clonality testing can be performed on DBS samples,
      thus improving the diagnostic and monitoring options for lymphoproliferative
      diseases in resource-limited settings. 

PMID- 23965170
TI  - The GMOseek matrix: a decision support tool for optimizing the detection of
      genetically modified plants.
AB  - BACKGROUND: Since their first commercialization, the diversity of taxa and the
      genetic composition of transgene sequences in genetically modified plants (GMOs)
      are constantly increasing. To date, the detection of GMOs and derived products is
      commonly performed by PCR-based methods targeting specific DNA sequences
      introduced into the host genome. Information available regarding the GMOs'
      molecular characterization is dispersed and not appropriately organized. For this
      reason, GMO testing is very challenging and requires more complex screening
      strategies and decision making schemes, demanding in return the use of efficient
      bioinformatics tools relying on reliable information. DESCRIPTION: The GMOseek
      matrix was built as a comprehensive, online open-access tabulated database which
      provides a reliable, comprehensive and user-friendly overview of 328 GMO events
      and 247 different genetic elements (status: 18/07/2013). The GMOseek matrix is
      aiming to facilitate GMO detection from plant origin at different phases of the
      analysis. It assists in selecting the targets for a screening analysis,
      interpreting the screening results, checking the occurrence of a screening
      element in a group of selected GMOs, identifying gaps in the available pool of
      GMO detection methods, and designing a decision tree. The GMOseek matrix is an
      independent database with effective functionalities in a format facilitating
      transferability to other platforms. Data were collected from all available
      sources and experimentally tested where detection methods and certified reference
      materials (CRMs) were available. CONCLUSIONS: The GMOseek matrix is currently a
      unique and very valuable tool with reliable information on GMOs from plant origin
      and their present genetic elements that enables further development of
      appropriate strategies for GMO detection. It is flexible enough to be further
      updated with new information and integrated in different applications and
      platforms.

PMID- 23965171
TI  - An ABC pleiotropic drug resistance transporter of Fusarium graminearum with a
      role in crown and root diseases of wheat.
AB  - FgABC1 (FGSG_04580) is predicted to encode a pleiotropic drug resistance class
      ABC transporter in Fusarium graminearum, a globally important pathogen of wheat.
      Deletion mutants of FgABC1 showed reduced virulence towards wheat in crown and
      root infection assays but were unaltered in infectivity on barley. Expression of
      FgABC1 during head blight and crown rot disease increases during the necrotrophic
      phases of infection suggestive of a role for FgABC1 in late infection stages in
      different tissue types. Deletion of FgABC1 also led to increased sensitivity of
      the fungus to the antifungal compound benalaxyl in culture, but the response to
      known cereal defence compounds, gramine, 2-benzoxazalinone and tryptamine was
      unaltered. FgABC1 appears to have a role in protecting the fungus from antifungal
      compounds and is likely to help combat as yet unidentified wheat defence
      compounds during disease development. 

PMID- 23965172
TI  - MU opioid receptor agonist-selective regulation of interleukin-4 in T
      lymphocytes.
AB  - Opioids are irreplaceable for the treatment of severe pain. However, opioid
      induced immunomodulation affects therapies. Here we report that treatment of
      human T lymphocytes with the opioids fentanyl, methadone, loperamide and beta
      endorphin resulted in a strong induction of the cytokine interleukin-4. In
      contrast, morphine and buprenorphine induced markedly and significantly lower
      levels of interleukin-4 mRNA and protein. These findings suggest agonist-biased
      MU opioid receptor signaling in T cells. In the future, better knowledge about
      agonist-specific immunomodulatory effects of opioids offers the possibility to
      select drugs for a therapy with more favorable and/or less detrimental side
      effects in immune cells. 

PMID- 23965173
TI  - Otolaryngologic findings in prepubertal obese children with sleep-disordered
      breathing.
AB  - OBJECTIVE: To evaluate otolaryngologic findings in obese prepubertal children
      with sleep-disordered breathing. METHODS: We prospectively evaluated 29 obese
      children referred by pediatric endocrinologist, complaining of snoring and
      without a history of nasal surgery or removal of the palatine tonsils and/or
      adenoids. Patients underwent ear, nose and throat (ENT) examination, endoscopy,
      measurements of weight, height, calculation of body mass index (BMI), assessment
      of BMI z-score and polysomnography, from which were divided into two groups:
      those with obstructive sleep apnea syndrome (nine children) and those with
      primary snoring (20 children). Then we proceeded to the statistical analysis of
      the data collected. RESULTS: The groups did not differ in age, gender, weight,
      height, BMI and BMI z-score. Among the findings of the ENT examination, the
      adenoid size was the only one that differed between the groups (p = 0.01).
      CONCLUSION: The evaluation of the adenoid size is an important in obese children
      with symptoms of sleep-disordered breathing and is related to the presence of
      obstructive sleep apnea syndrome.

PMID- 23965174
TI  - Chronic hyponatriemia associated with Rett syndrome.

PMID- 23965175
TI  - Carbonic anhydrase inhibitors: synthesis and inhibition of the human carbonic
      anhydrase isoforms I, II, VII, IX and XII with benzene sulfonamides incorporating
      4,5,6,7-tetrabromophthalimide moiety.
AB  - A series of 4,5,6,7-tetrabromo-1,3-dioxoisoindolin-2-yl benzenesulfonamide
      derivatives (compounds 1-8) was synthesized by reaction of benzene sulfonamide
      derivatives with 4,5,6,7-tetrabromophthalic anhydride moiety. These new
      sulfonamides were investigated as inhibitors of the zinc metalloenzyme carbonic
      anhydrase (CA, EC 4.2.1.1) and more specifically against the human (h) cytosolic
      isoforms hCA I, II and VII and the transmembrane tumor-associated isoform hCA IX
      and XII. The new compounds were good hCA I inhibitors (Kis in the range of 143 to
      >10,000nM), but were moderately effective, as hCA II inhibitors (Kis of 47-190nM)
      and poor hCA VII inhibitors (Kis in the range of 54-175nM) compared to
      acetazolamide. The tumor-associated hCA IX was effectively inhibited with Kis
      ranging between 8.5 and 234nM and hCA XII with inhibition constants in the range
      of 6.1-197nM with high selectivity ratio. The structure-activity relationship
      (SAR) with this series of sulfonamides is straightforward, with the main features
      leading to good activity for each isoforms being established. The high sequence
      hCA alignment homology and molecular docking study of compounds was performed to
      rationalize the SAR reported over here. 

PMID- 23965176
TI  - TLR-3 receptor activation protects the very immature brain from ischemic injury.
AB  - BACKGROUND: We have shown that preconditioning by lipopolysaccharide (LPS) will
      result in 90% reduction in ischemic brain damage in P7 rats. This robust LPS
      neuroprotection was not observed in P3 or P5 pups (corresponding to human
      premature infant). LPS is a known Toll-like receptor 4 (TLR-4) ligand. We
      hypothesized that TLRs other than TLR-4 may mediate preconditioning against
      cerebral ischemic injury in the developing brain. METHODS: TLR-2, TLR-3, TLR-4,
      and TLR-9 expression was detected in brain sections from P3, P5, and P7 rats by
      immuno-staining. In subsequent experiments, P5 rats were randomly assigned to TLR
      3 specific agonist, poly I:C, or saline treated group. At 48 h after the
      injections, hypoxic-ischemic (HI) injury was induced by unilateral carotid artery
      ligation followed by hypoxia for 65 min. Brains were removed 1 week after HI
      injury and infarct volumes were compared in H&E stained sections between the two
      groups. RESULTS: TLR-2 and TLR-3 were highly expressed in brains of P3 and P5 but
      not in P7 rats. The number of TLR-4 positive cells was lower in P3 and P5
      compared to P7 brains (P <0.05). TLR-3 was predominately expressed in P5 pups (P
      <0.05). There was no significant difference in TLR-9 expression in the three age
      groups. There was a significant reduction in infarct volume (P=0.01) in poly I:C
      compared to saline pre-treated P5 pups. Pre-treatment with poly I:C downregulated
      NF-kappaB and upregulated IRF3 expression in P5 rat ischemic brains. Pre
      treatment with poly I:C did not offer neuroprotection in P7 rat brains.
      CONCLUSION: TLRs expression and function is developmentally determined. Poly I:C
      induced preconditioning against ischemic injury may be mediated by modulation of
      TLR-3 signaling pathways. This is the first study to show that TLR-3 is expressed
      in the immature brain and mediates preconditioning against ischemic injury.

PMID- 23965177
TI  - Charcot neuroarthropathy of the foot and ankle: a review.
AB  - Charcot neuroarthropathy is a limb-threatening, destructive process that occurs
      in patients with neuropathy associated with medical diseases such as diabetes
      mellitus. Clinicians' treating diabetic patients should be vigilant in
      recognizing the early signs of acute Charcot neuroarthropathy, such as pain,
      warmth, edema, or pathologic fracture in a neuropathic foot. Early detection and
      prompt treatment can prevent joint and bone destruction, which, if untreated, can
      lead to morbidity and high-level amputation. A high degree of suspicion is
      necessary. Once the early signs have been detected, prompt immobilization and
      offloading are important. Treatment should be determined on an individual basis,
      and it must be determined whether a patient can be treated conservatively or will
      require surgical intervention when entering the chronic phase. If diagnosed
      early, medical and conservative measures only will be required. Surgery is
      indicated for patients with severe or unstable deformities that, if untreated,
      will result in major amputations. A team approach that includes a foot and ankle
      surgeon, a diabetologist, a physiotherapist, a medical social councilor, and,
      most importantly, the patient and immediate family members is vital for
      successful management of this serious condition.

PMID- 23965178
TI  - Validity and reliability of the Achilles tendon total rupture score.
AB  - The best treatment of acute Achilles tendon rupture remains debated. Patient
      reported outcome measures have become cornerstones in treatment evaluations. The
      Achilles tendon total rupture score (ATRS) has been developed for this purpose
      but requires additional validation. The purpose of the present study was to
      validate a Danish translation of the ATRS. The ATRS was translated into Danish
      according to internationally adopted standards. Of 142 patients, 90 with previous
      rupture of the Achilles tendon participated in the validity study and 52 in the
      reliability study. The ATRS showed moderately strong correlations with the
      physical subscores of the Medical Outcomes Study 36-item Short-Form Health Survey
      (r = .70 to .75; p < .0001) and Victorian Institute of Sports Assessment-Achilles
      questionnaire (r = .71; p < .0001). Test-retest of the ATRS showed no significant
      difference in the mean (2.41; p = .07). The limits of agreement were +/-18.53. A
      strong correlation was found between test and retest (intercorrelation
      coefficient .908); the standard error of measurement was 6.7, and the minimal
      detectable change was 18.5. The Danish version of the ATRS showed moderately
      strong criterion validity. For study and follow-up purposes, the ATRS seems
      reliable for comparisons of groups of patients. Its usability is limited for
      repeated assessment of individual patients. The development of analysis
      guidelines would be desirable. 

PMID- 23965179
TI  - Use of tensioned olive wires through a neutralization plate for syndesmotic
      reduction.
AB  - Ankle fractures are a common osteologic outcome from trauma. These fracture
      patterns include a variety of concomitant soft tissue disruptions, including
      diastasis. Surgical treatment of a syndesmotic injury can be performed in
      conjunction with open reduction with internal fixation. The present technique
      guide demonstrates the use of pre-existing hardware, after open reduction with
      internal fixation from a previous ankle fracture, with an Ilizarov fixation
      construct to percutaneously reduce a bimalleolar equivalent fracture and
      diastasis to the syndesmosis. 

PMID- 23965180
TI  - Protocol for a double-blind randomised controlled trial of low dose intradermal
      grass pollen immunotherapy versus a histamine control on symptoms and medication
      use in adults with seasonal allergic rhinitis (PollenLITE).
AB  - BACKGROUND: Subcutaneous immunotherapy with high dose grass pollen (typically
      microgram quantities) was first described over 100 years ago. This treatment
      suppresses allergen-induced cutaneous late responses, with lesser effects on
      early responses. We previously reported that repeated 2-weekly intradermal
      injections of grass pollen - containing approximately 7 ng of major allergen Phl
      p 5 - led to a progressive suppression of the allergen-induced cutaneous
      response, and that by the sixth injection, this was inhibited by over 90%. The
      purpose of this trial is to investigate the clinical efficacy of intradermal
      desensitisation with low doses (i.e. nanogram quantities) of grass pollen
      allergen for seasonal allergic rhinitis. METHODS/DESIGN: The Pollen Low dose
      Intradermal therapy Evaluation (PollenLITE) is a single centre double-blind
      randomised parallel group controlled trial of the efficacy and safety of
      intradermal grass pollen injections plus standard treatment, versus histamine
      injections plus standard treatment, in adults with moderate-severe grass pollen
      induced allergic rhinitis ('summer hay fever'). A minimum of ninety adults with a
      history of moderate-severe persistent allergic rhinitis during the UK grass
      pollen season will be randomised into two equal groups to receive 7 or 8
      intradermal injections of grass pollen extract (containing approximately 7 ng of
      major allergen Phl p 5) or histamine, before the grass pollen season. In the
      summer, participants will score their symptoms, medication requirements, visual
      analogue scores, and complete EuroQOL (EQ-5D-5 L) and mini Rhinoconjunctivitis
      Quality of Life Questionnaires. Global assessments will also be recorded at the
      end of the pollen season. Blood samples will be collected from all participants
      for mechanistic immune assays. Skin punch biopsies will also be collected in 40
      participants selected at random from intradermal injection sites after the grass
      pollen season for mechanistic assays. Finally, to investigate if the
      desensitising effect of intradermal immunotherapy on cutaneous responses is long
      lasting, all participants will be randomised to receive a follow up intradermal
      injection after 3, 6 or 12 months with measurement of early and late response
      sizes. DISCUSSION: Randomisation began in February 2013 and the final participant
      will complete the trial protocol in August 2014. TRIAL REGISTRATION: ISRCTN
      78413121EudraCT number 2012-002193-31.

PMID- 23965182
TI  - Acceptability of human papillomavirus vaccination among male university students
      in the United Arab Emirates.
AB  - OBJECTIVE: To assess the knowledge about and acceptability of human
      papillomavirus (HPV) vaccination among male university students in the United
      Arab Emirates (UAE). METHODS: Between June and August 2012 we approached 356 male
      university students from the UAE and asked them to fill out a 12-item self
      administered questionnaire. RESULTS: Knowledge of HPV was low among the
      university students who participated (32%). Less than half of the students (46%)
      indicated they would accept HPV vaccination, and around 30% were unsure of their
      decision. Safety (68%), protection of their female partner (65%) and doctor's
      recommendation (64%) were rated as the factors most likely to increase the uptake
      of HPV vaccination among participating students. The factors rated most likely to
      stop students from using the vaccine were fear of side effects (85%), absence of
      clear benefits (38%) and objections from a religious authority (25%). Marital
      status and sexual activity were associated with greater knowledge of HPV but not
      with greater acceptance of vaccination among university students in the UAE.
      CONCLUSION: Overall acceptability of and knowledge about HPV infection and
      vaccination were low in a sample of male university students in the UAE. Marital
      status and sexual activity are associated with greater knowledge of HPV infection
      but have no effect on the acceptability of HPV vaccination.

PMID- 23965183
TI  - Immigrant women's experiences of postpartum depression in Canada: a protocol for
      systematic review using a narrative synthesis.
AB  - BACKGROUND: Literature documents that immigrant women in Canada have a higher
      prevalence of postpartum depression symptomatology than Canadian-born women.
      There exists a need to synthesize information on the contextual factors and
      social determinants of health that influence immigrant women's reception of and
      behavior in accessing existing mental health services. Our research question is:
      what are the ethnoculturally defined patterns of help-seeking behaviors and
      decision-making and other predictive factors for therapeutic mental health care
      access and outcomes with respect to postpartum depression for immigrant women in
      Canada? METHODS/DESIGN: Our synthesis incorporates a systematic review using
      narrative synthesis of reports (peer- and non-peer reviewed) of empirical
      research and aims to provide stakeholders with perspectives on postpartum mental
      health care services as experienced by immigrant women. To reach this goal we are
      using integrated knowledge translation, thus partnering with key stakeholders
      throughout the planning, implementation and dissemination stages to ensure topic
      relevancy and impact on future practice and policy. The search and selection
      strategies draw upon established systematic review methodologies as outlined by
      the Centre for Reviews and Dissemination and also incorporate guidelines for
      selection and appraisal of gray literature. Two search phases (a database and a
      gray literature phase) will identify literature for screening and final selection
      based on an inclusion/exclusion checklist. Quality appraisal will be performed
      using the tools produced by the Centre for Evidence Based Management. The
      narrative synthesis will be informed by Popay et al. (2006) framework using
      identified tools for each of its four elements. The integrated knowledge
      translation plan will ensure key messages are delivered in an audience-specific
      manner to optimize their impact on policy and practice change throughout health
      service, public health, immigration and community sectors. DISCUSSION: The
      narrative synthesis methodology will facilitate understandings and
      acknowledgement of the broader influences of theoretical and contextual
      variables, such as race, gender, socio-economic status, pre-migration history and
      geographical location. Our review aims to have a substantive and sustainable
      impact on health outcomes, practice, programs and/or policy in the context of
      postpartum mental health of immigrant women. PROSPERO registration number
      CRD42012003020.

PMID- 23965181
TI  - Comparison of fondaparinux with low molecular weight heparin for venous
      thromboembolism prevention in patients requiring rigid or semi-rigid
      immobilization for isolated non-surgical below-knee injury.
AB  - BACKGROUND: In several small studies, anticoagulant therapy reduced the incidence
      of venous thromboembolism (VTE) in patients with isolated lower-limb injuries.
      OBJECTIVES: To compare the efficacy and safety of fondaparinux 2.5 mg (1.5 mg in
      patients with a creatinine clearance between 30 and 50 mL min(-1) ) over
      nadroparin 2850 anti-factor Xa IU. PATIENTS AND METHODS: In this international,
      multicenter, randomized, open-label study, patients with an isolated non-surgical
      unilateral below-knee injury having at least one additional major risk factor for
      VTE and requiring, in the Investigator's opinion, rigid or semi-rigid
      immobilization for 21-45 days with thromboprophylaxis up to complete mobilization
      received subcutaneously once-daily either fondaparinux or nadroparin. The primary
      efficacy outcome was the composite of VTE (symptomatic or ultrasonographically
      detected asymptomatic deep vein thrombosis of the lower limb or symptomatic
      pulmonary embolism) and death up to complete mobilization. The main safety
      outcome was major bleeding. RESULTS: We randomized 1349 patients (mean age 46
      years): 88.7% had a bone fracture, and 83.8% had a plaster cast fitted (mean
      duration of immobilization, 34 days). The primary efficacy outcome occurred in 15
      of 584 patients (2.6%) in the fondaparinux group and 48 of 586 patients (8.2%) in
      the nadroparin group (odds ratio, 0.30; 95% confidence interval [CI], 0.15-0.54;
      P < 0.001). A single major bleed was experienced by fondaparinux-treated patients
      and none by nadroparin-treated patients. These results were maintained up to the
      end of follow-up. CONCLUSIONS: Fondaparinux 2.5 mg day(-1) may be a valuable
      therapeutic option over nadroparin 2850 anti-FXa IU day(-1) for preventing VTE
      after below-knee injury requiring prolonged immobilization in patients with
      additional risk factors.

PMID- 23965184
TI  - S1 is associated with chronic low back pain: a functional and structural MRI
      study.
AB  - A fundamental characteristic of neural circuits is the capacity for plasticity in
      response to experience. Neural plasticity is associated with the development of
      chronic pain disorders. In this study, we investigated 1) brain resting state
      functional connectivity (FC) differences between patients with chronic low back
      pain (cLBP) and matched healthy controls (HC); 2) FC differences within the cLBP
      patients as they experienced different levels of endogenous low back pain evoked
      by exercise maneuvers, and 3) morphometric differences between cLBP patients and
      matched HC. We found the dynamic character of FC in the primary somatosensory
      cortex (S1) in cLBP patients, i.e., S1 FC decreased when the patients experienced
      low intensity LBP as compared with matched healthy controls, and FC at S1
      increased when cLBP patients experienced high intensity LBP as compared with the
      low intensity condition. In addition, we also found increased cortical thickness
      in the bilateral S1 somatotopically associated with the lower back in cLBP
      patients as compared to healthy controls. Our results provide evidence of
      structural plasticity co-localized with areas exhibiting FC changes in S1 in cLBP
      patients.

PMID- 23965185
TI  - Role of hepatitis E virus antigen in confirming active viral replication in
      patients with acute viral hepatitis E infection.
AB  - BACKGROUND: Demonstration of active viral replication is important in
      serologically confirmed cases of hepatitis E virus (HEV) infection to assess
      prognosis. Detection of HEV RNA by reverse transcriptase polymerase chain
      reaction (rtPCR) is the gold standard for demonstration of active viremia.
      OBJECTIVES: The present study was designed to compare the diagnostic utility of
      HEV antigen (Ag) with HEV IgM and HEV rtPCR in detecting the active viral
      replication. STUDY DESIGN: Blood samples from 156 probable cases of acute viral
      hepatitis (AVH) were collected. Screening for hepatitis B surface antigen
      (HBsAg), antibody to hepatitis C virus (anti HCV), IgM antibody to hepatitis A
      virus (HAV IgM) was done on the Architect platform (Abbott Laboratories, IL,
      USA). HEV IgM ELISA (Wantai Biological, Beijing, China), HEV-Ag ELISA (Wantai
      Biological, Beijing, China) and HEV rtPCR were done on all the samples. RESULTS:
      Out of 156 AVH cases in 56 (35.8%) a diagnosis of HEV was confirmed. Positivity
      being; anti-HEV IgM 44/56, HEV RNA 20/56, and HEV antigen 17/56 in established
      cases. Male to female ratio was 3:1. The median age was 40 (range 14-71) years.
      HEV Ag showed a good concordance with HEV RNA (k=0.635, p<0.001). However HEV IgM
      did not show any concordance with HEV RNA (k=0.14). CONCLUSION: HEV antigen assay
      can be used as an additional diagnostic marker to confirm active viral
      replication in serologically positive samples.

PMID- 23965187
TI  - Importance of patient selection for patient-controlled epidural analgesia (PCEA),
      as even low-concentration solutions may lead to a very high block.
AB  - Patient-controlled epidural analgesia (PCEA) is an excellent choice of analgesia
      technique in labor; however, patient selection for such treatment is important. A
      14 year old healthy parturient receiving PCEA had a very high block due to
      patient noncompliance. 

PMID- 23965186
TI  - Reactive oxygen species, ageing and the hormesis police.
AB  - For more than 50 years, the free radical theory served as the paradigm guiding
      most investigations of ageing. However, recent studies in a variety of organisms
      have identified conceptual and practical limitations to this theory. Some of
      these limitations are related to the recent discovery that caloric restriction
      and other experimental manipulations promote longevity by inducing hormesis
      effects in association with increased reactive oxygen species (ROS). The
      beneficial role of ROS in lifespan extension is consistent with the essential
      role of these molecules in cell signalling. However, the identity of specific
      forms of ROS that promote longevity remains unclear. In this article, we argue
      that in several model systems, hydrogen peroxide plays a crucial role in the
      induction of hormesis. 

PMID- 23965188
TI  - The effect of sevoflurane versus desflurane on the incidence of upper respiratory
      morbidity in patients undergoing general anesthesia with a Laryngeal Mask Airway:
      a meta-analysis of randomized controlled trials.
AB  - STUDY OBJECTIVE: To compare the incidence of upper airway morbidity with
      sevoflurane versus desflurane in patients undergoing general anesthesia with a
      Laryngeal Mask Airway (LMA). DESIGN: Systematic review and meta-analysis of
      randomized controlled trials (RCTs). SETTING: Operating room of an academic
      medical center. MEASUREMENTS: A systematic review of RCTs of patients receiving
      general anesthesia with a LMA was performed. Sevoflurane and desflurane were used
      for maintenance of anesthesia in the RCTs. A wide search was performed to
      identify RCTs comparing desflurane with sevoflurane on the incidence of upper
      respiratory adverse events in patients undergoing surgery with a LMA. The primary
      outcomes were incidence of cough and laryngospasm. A random-effects model was
      used to perform quantitative analysis. MAIN RESULTS: Data originating from 7
      studies comprising 657 subjects were analyzed. The confidence interval (CI) was
      large relative to a clinically significant difference in the incidence of overall
      cough and laryngospasm in patients receiving desflurane versus sevoflurane (odds
      ratio [OR; 95% CI] of 1.44 [0.49 - 4.1] and 3.06 [0.43 - 21.62]), respectively.
      The incidence of cough at emergence was greater in subjects receiving desflurane
      compared with sevoflurane (OR [95% CI] of 2.43 [1.2 - 4.7], number needed to harm
      [NNH] = 9.0); however, the analysis was limited by the presence of an asymmetric
      funnel plot suggesting the possibility of publication bias. CONCLUSIONS: There is
      a lack of evidence that desflurane causes a greater incidence of upper airway
      adverse events than sevoflurane in patients undergoing general anesthesia with a
      LMA.

PMID- 23965189
TI  - Methodologies of anesthesia information management system development.

PMID- 23965190
TI  - Sequential lung isolation using a bronchial blocker (EZ-Blocker) for bilateral
      dorsal sympathectomy.

PMID- 23965191
TI  - Comparison between the analgesic efficacy of transversus abdominis plane (TAP)
      block and placebo in open retropubic radical prostatectomy: a prospective,
      randomized, double-blinded study.
AB  - STUDY OBJECTIVE: To compare the efficacy of ultrasound-guided tansversus
      abdominis plane (TAP) block with placebo for postoperative analgesia after
      retropubic radical prostatectomy (RRP). DESIGN: Prospective, randomized, double
      blinded study. SETTING: Tertiary-care Veterans Affairs (VA) hospital. PATIENTS:
      ASA physical status 1, 2, and 3 patients scheduled for RRP. INTERVENTIONS:
      Patients were randomized to two groups: the TAP group and the control group. All
      patients underwent an ultrasound-guided TAP block procedure after induction of
      general anesthesia and received either local anesthetic (TAP group) or normal
      saline (control group). MEASUREMENTS: Opioid use and verbal analog pain scores at
      1, 6, 12, and 24 hours after surgery were recorded, as was the frequency of side
      effects. Times to ambulation and first oral intake also were recorded. MAIN
      RESULTS: The TAP block group had lower pain scores and required less total opioid
      in the first 24 hours after surgery. Time to first oral intake and time to
      ambulation were similar between the two groups. CONCLUSION: The TAP block has
      early benefits in postoperative analgesia after RRP.

PMID- 23965192
TI  - Continuous hemoglobin monitoring during massive blood transfusion in a
      multivisceral pediatric transplant patient.
AB  - A 10 year old, 25 kg girl, who was formerly a conjoined twin at the heart,
      diaphragm, liver, duodenum, bile ducts, and intestine, was admitted for a repeat
      liver, small bowel, pancreas, and kidney multivisceral transplant after having
      intestinal and liver failure. Intraoperatively, the patient had excessive
      bleeding, coagulopathy, and acidosis. Pulse co-oximetry was used for continuous
      monitoring of hemoglobin (Hb) during the procedure. Although noninvasive Hb
      appeared to follow a trend that correlated with arterial Hb concentration, it did
      not show accurate agreement with measured values from intermittent blood gas
      analysis. It may not be reliable during cases with abnormal physiology, rapid
      blood loss, and massive transfusion. 

PMID- 23965193
TI  - Cardiac arrest in conjuction with hypoglycemia and spinal anesthesia.

PMID- 23965194
TI  - Standardization is the better tool to achieving competency for clinical
      management of awake craniotomy.

PMID- 23965195
TI  - A basic needs assessment of Kenyan health care practitioners' training and
      ability in providing resuscitation management for patients in Mbagathi Hospital,
      Nairobi.
AB  - STUDY OBJECTIVE: To determine if health care providers at one district hospital
      in Nairobi, Kenya, possess the training and confidence necessary to attend to
      basic needs for patient resuscitation. DESIGN: Prospective cohort study. SETTING:
      Mbagathi District Hospital, Nairobi, Kenya, a 300-bed, government district-level
      health care facility serving over one million Kenyans. SUBJECTS: 21 medical
      officers, clinical officers, medical officer and clinical officer interns, and
      nurses. MEASUREMENTS: An investigator-designed survey, the Self Assessment of
      Clinical Skills, designed to assess training and level of confidence in
      addressing basic resuscitation, was administered. MAIN RESULTS: 80% of
      respondents have been taught how to maintain a patent airway, but 22% felt less
      than confident in their ability. Nearly two thirds (62%) of respondents had not
      been trained to use a pulse oximeter. 100% of respondents felt they would benefit
      from additional training in airway and pulse oximetry assessment. While 90%
      reported that they had been taught to treat hypotension and 76% had experience
      treating hypotension, only 62% felt confident in their ability to treat
      hypotension. 95% desired additional training in hypotension management. 85%
      wanted additional training in measuring blood pressure, and every respondent
      desired additional training in the other circulatory monitoring skills listed on
      the survey. CONCLUSIONS: Providers of the Mbagathi District Hospital, Nairobi,
      report a lack of confidence in recognizing basic resuscitation needs, and they
      desire additional training.

PMID- 23965196
TI  - Using the problem-based learning discussion (PBLD) to facilitate research.

PMID- 23965197
TI  - Transient hemidiaphragmatic paresis after ultrasound-guided lateral sagittal
      infraclavicular block.
AB  - As compared with medial approaches for the infraclavicular brachial plexus block,
      lateral approaches generally have no impact on the phrenic nerve or pulmonary
      function. A patient experienced transient hemidiaphragmatic paresis after
      ultrasound-guided lateral sagittal infraclavicular block for lower arm surgery.
      An accessory phrenic nerve, ie, an anatomical variation, may have been the
      mechanism of transient hemidiaphragmatic paresis in this patient. 

PMID- 23965198
TI  - Risk factors for predicting postoperative complications after open infrarenal
      abdominal aortic aneurysm repair: results from a single vascular center in China.
AB  - STUDY OBJECTIVE: To identify the risk factors of, and develop a prediction model
      for, postoperative complications of patients undergoing infrarenal abdominal
      aortic aneurysm (IAAA) repair. DESIGN: Retrospective analysis. SETTING: Vascular
      surgery center of a university hospital. MEASUREMENTS: The clinical data of 316
      IAAA cases were collected from January 2004 to October 2010 at a single vascular
      center in China. Postoperative complications were observed within 30 days after
      surgery. Patient-specific and operation-specific characteristics were analyzed in
      relation to postoperative complications using multiple logistic regression
      analysis. MAIN RESULTS: Overall incidence of postoperative complications and
      overall 30-day mortality of IAAA repair patients were 48.4% (153/316) and 8.8%
      (28/316), respectively. Postoperative complications involved pulmonary (18.9%),
      cardiac (14.2%), renal (7.3%), gastrointestinal (5.4%), neurologic (1.3%), and
      hepatic (0.9%) systems, and acute arterial embolism of the lower limb occurred in
      1.3% of cases. Risk factors were age [> 65 yrs; odds ratio (OR) 1.6], aortic
      occlusion time (> 90 min; OR 2.4), history of chronic obstructive pulmonary
      disease (COPD; OR 4.4), emergency operation (OR 6.1), and history of cardiac
      dysfunction (OR 2.1). CONCLUSIONS: A combination of age, COPD, emergency
      operation, history of cardiac dysfunction and aortic occlusion time has
      significant impact on postoperative complications after open IAAA repair.

PMID- 23965200
TI  - Lessons from providing total intravenous anesthesia (TIVA) to a morbidly obese
      patient (294 kg [648 lbs], body mass index 85.5 kg/m2).

PMID- 23965199
TI  - Comparison of stroke volume and fluid responsiveness measurements in commonly
      used technologies for goal-directed therapy.
AB  - STUDY OBJECTIVE: To compare stroke volume (SV) and preload responsiveness
      measurements from different technologies with the esophageal Doppler monitor
      (EDM). DESIGN: Prospective measurement study. SETTING: Operating room. PATIENTS:
      20 ASA physical status 3 patients undergoing vascular, major urological, and
      bariatric surgery. INTERVENTIONS: Subjects received fluids using a standard
      Doppler protocol of 250 mL of colloid administered until SV no longer increased
      by >10%, and again when the measured SV decreased by 10%. MEASUREMENTS:
      Simultaneous readings of SV, stroke volume variation (SVV) and pulse pressure
      variation (PPV) from the LiDCOrapid, and SVV from the FloTrac/Vigileo were
      compared with EDM measurements. The pleth variability index (PVI) also was
      recorded. MAIN RESULTS: No correlation was seen in percentage SV change as
      measured by either the LiDCOrapid (r=0.05, P=0.616) or FloTrac (r=0.09, P= 0.363)
      systems compared with the EDM. Correlation was present between the LiDCOrapid and
      FloTrac (r=0.515, P<0.0001). Percentage error compared with the EDM was 81% for
      the FloTrac and 90% for the LiDCOrapid. SVV as measured by LiDCOrapid differed
      for fluid responders and nonresponders (10% vs 7%; P=0.021). Receiver operator
      curve analysis to predict a 10% increase in SV from the measured variables showed
      an area under the curve of 0.57 (95% CI 0.43-0.72) for SVV(FloTrac), 0.64 (95% CI
      0.52-0.78) for SVV(LiDCO), 0.61 (95% CI 0.46 -0.76) for PPV, and 0.59 (95% CI
      0.46 -0.71) for PVI. CONCLUSIONS: Stroke volume as measured by the FloTrac and
      LiDCOrapid systems does not correlate with the esphageal Doppler, has poor
      concordance, and a clinically unacceptable percentage error. The predictive value
      of the fluid responsiveness parameters is low, with only SVV measured by the
      LiDCOrapid having clinical utility.

PMID- 23965201
TI  - Training anesthesiology residents in providing anesthesia for awake craniotomy:
      learning curves and estimate of needed case load.
AB  - STUDY OBJECTIVE: To measure the learning curves of residents in anesthesiology in
      providing anesthesia for awake craniotomy, and to estimate the case load needed
      to achieve a "good-excellent" level of competence. DESIGN: Prospective study.
      SETTING: Operating room of a university hospital. SUBJECTS: 7 volunteer residents
      in anesthesiology. MEASUREMENTS: Residents underwent a dedicated training program
      of clinical characteristics of anesthesia for awake craniotomy. The program was
      divided into three tasks: local anesthesia, sedation-analgesia, and
      intraoperative hemodynamic management. The learning curve for each resident for
      each task was recorded over 10 procedures. Quantitative assessment of the
      individual's ability was based on the resident's self-assessment score and the
      attending anesthesiologist's judgment, and rated by modified 12 mm Likert scale,
      reported ability score visual analog scale (VAS). This ability VAS score ranged
      from 1 to 12 (ie, very poor, mild, moderate, sufficient, good, excellent). The
      number of requests for advice also was recorded (ie, resident requests for
      practical help and theoretical notions to accomplish the procedures). MAIN
      RESULTS: Each task had a specific learning rate; the number of procedures
      necessary to achieve "good-excellent" ability with confidence, as determined by
      the recorded results, were 10 procedures for local anesthesia, 15 to 25
      procedures for sedation-analgesia, and 20 to 30 procedures for intraoperative
      hemodynamic management. CONCLUSIONS: Awake craniotomy is an approach used
      increasingly in neuroanesthesia. A dedicated training program based on learning
      specific tasks and building confidence with essential features provides "good
      excellent" ability.

PMID- 23965202
TI  - Sustained airway pressure after transient occlusion of a valve venting a self
      inflating manual resuscitator.

PMID- 23965203
TI  - Anesthesia for irreversible electroporation of hepatic malignant tumors.

PMID- 23965204
TI  - Repeated spinal anesthesia in a tetraparetic patient with Guillain-Barre
      syndrome.
AB  - A 78 year old man with tetraparesis, reduced forced vital capacity, and
      neurogenic bladder dysfunction due to Guillain-Barre syndrome was admitted for
      elective transurethral prostate resection and percutaneous lithotripsy of a
      bladder stone. On the sixth postoperative day, he was readmitted for emergency
      evacuation of a clot in the bladder. Both operations were performed with spinal
      anesthesia (hyperbaric bupivacaine + fentanyl) without neurologic sequelae. 

PMID- 23965205
TI  - Effects of the menstrual cycle on injection pain due to rocuronium.
AB  - STUDY OBJECTIVE: To investigate the effect of the menstrual cycle on rocuronium
      injection pain. DESIGN: Prospective, randomized, double-blinded study. SETTING:
      Academic medical center. PATIENTS: 80 ASA physical status 1 and 2 women scheduled
      for elective surgery with general anesthesia. MEASUREMENTS: Patients were divided
      into two groups according to their time in the menstrual cycle. Forty patients at
      days 8 to 12 of the menstrual cycle were considered to be at the follicular phase
      (Group F), and 40 patients at days 20 to 24 of the menstrual cycle were
      considered to be at the luteal phase (Group L).Withdrawal movements were
      recorded. MAIN RESULTS: Overall frequency of withdrawal movements was
      significantly higher in Group L than Group F (P < 0.001). The mean withdrawal
      movement score was 1.77 +/- 0.76 in Group L and 0.52 +/- 0.67 in Group F.
      CONCLUSION: Menstrual cycle phases affect the severity of rocuronium injection
      pain. Women exhibit greater pain sensitivity from rocuronium injection in the
      luteal phase than the follicular phase.

PMID- 23965206
TI  - Effect of tranexamic acid on reducing postoperative blood loss in combined
      hypotensive epidural anesthesia and general anesthesia for total hip replacement.
AB  - STUDY OBJECTIVE: To determine whether the use of tranexamic acid in the setting
      of hypotension induced by hypotensive epidural anesthesia (HEA) has any
      additional beneficial effects in reducing perioperative blood loss and
      transfusion requirements in total hip replacement. DESIGN: Prospective,
      randomized, double-blinded trial. SETTING: University-affiliated hospital.
      PATIENTS: 68 adult, ASA physical status 1 and 2 patients undergoing primary
      unilateral cementless total hip replacement with general anesthesia and HEA.
      INTERVENTIONS: The HEATA group received a bolus dose of 15 mg/kg of tranexamic
      acid before surgical incision, followed by a continuous 15 mg/kg infusion until
      skin closure. The HEA group received normal saline instead of tranexamic acid in
      the same manner. MEASUREMENTS: Intraoperative blood loss was measured using the
      difference between the weights of used gauze and the original unused gauze, in
      addition to the blood volume accumulated in suction bottles. Postoperative blood
      loss was considered to be the amount of blood accumulated in drainage bags. MAIN
      RESULTS: There was no significant difference in intraoperative blood loss between
      the HEA and HEATA groups (251.8 +/- 109.9 mL vs. 234.9 +/- 93.9 mL), but
      postoperative blood loss was significantly less in the HEATA group than the HEA
      group (439.3 +/- 171. 6 mL vs. 1074.4 +/- 287.1 mL), as was total cumulative
      blood loss (674.2 +/- 216.4 mL vs. 1326.2 +/- 347.8 mL). There was no significant
      difference in intraoperative transfusion incidences, but postoperative
      transfusion was greater in the HEA group than the HEATA group. CONCLUSIONS:
      Administration of tranexamic acid combined with hypotensive epidural anesthesia
      reduced postoperative and total accumulative blood loss and transfusion
      requirements more than did hypotensive epidural anesthesia alone.

PMID- 23965207
TI  - Anesthetic management of an infant with Joubert syndrome for cardiac surgery.
AB  - The anesthetic implications of Joubert syndrome in an infant who required cardiac
      surgery using cardiopulmonary bypass (CPB) is presented. Children with Joubert
      syndrome present with central apnea due to malformations in the midbrain and
      cerebellum. These patients have a marked sensitivity to opioids. The use of
      dexmedetomidine along with remifentanil was effective in this case. 

PMID- 23965208
TI  - Paraneoplastic limbic encephalitis in a patient with adenocarcinoma of the colon:
      a case report.
AB  - Paraneoplastic limbic encephalitis is a rare clinical entity characterized by the
      development of neuropsychiatric symptoms associated with malignancies. A case of
      a woman who presented to the Emergency Department with abdominal pain,
      hyperglycemia, and altered mental status is presented. After initial
      stabilization and correction of hyperglycemia the patient underwent emergency
      surgery. Laparotomy showed marked dilatation and gangrenous changes of the colon
      and tumor in the sigmoid colon. She was mechanically ventilated and remained
      ventilator-dependent for 42 days. Most of the time she was febrile; fever
      persisted with peaks up to 40 degrees  C despite various antibiotic treatments.
      On neurological examination, the patient was somnolent with left-sided
      hemiparesis. Magnetic resonance imaging (MRI) showed hyperintensities in both
      hippocampal areas, and electroencephalography (EEG) showed sharp-wave activity in
      the temporal lobes. Cerebrospinal fluid (CSF) examination showed slightly
      elevated protein levels, and laboratory assessments showed an elevated titer of
      anti-Yo antibodies. Although we do not have pathological confirmation of limbic
      encephalitis, the diagnosis of paraneoplastic limbic encephalitis was presumed on
      the basis of MRI findings, EEG abnormality, elevated CSF protein, positive anti
      YO antibodies, and neurological findings. 

PMID- 23965209
TI  - Inadequate emergence after anesthesia: emergence delirium and hypoactive
      emergence in the Postanesthesia Care Unit.
AB  - STUDY OBJECTIVE: To evaluate the frequency, determinants, and outcome of
      inadequate emergence after elective surgery in the Postanesthesia Care Unit
      (PACU). DESIGN: Prospective observational study. SETTING: 12-bed PACU of a
      tertiary-care hospital in a major metropolitan area. PATIENTS: 266 adult patients
      admitted to the PACU. INTERVENTION: To evaluate inadequate emergence, the
      Richmond Agitation and Sedation Scale (RASS) was administered to patients 10
      minutes after their admission to the PACU. MEASUREMENTS: Demographic data,
      perioperative variables, and postoperative length of stay (LOS) in the PACU and
      the hospital were recorded. MAIN RESULTS: 40 (15%) patients showed symptoms of
      inadequate emergence: 17 patients (6.4%) screened positive for emergence delirium
      and 23 patients (8.6%) showed hypoactive emergence. Determinants of emergence
      delirium were longer duration of preoperative fasting (P = 0.001), higher visual
      analog scale (VAS) scores for pain (P = 0.002), and major surgical risk (P =
      0.001); these patients had a higher frequency of postoperative delirium (P =
      0.017) and had higher nausea VAS score 6 hours after surgery (P = 0.001).
      Determinants of hypoactive emergence were duration of surgery (P = 0.003), amount
      of crystalloids administered during surgery (P = 0.002), residual neuromuscular
      block (P < 0.001), high-risk surgery (P = 0.002), and lower core temperature on
      PACU admission (P = 0.028); these patients also had more frequent residual
      neuromuscular block (P < 0.001) postoperative delirium (P < 0.001), and more
      frequent adverse respiratory events (P = 0.02). Patients with hypoactive
      emergence had longer PACU and hospital LOS. CONCLUSIONS: Preventable determinants
      for emergence delirium were higher postoperative pain scores and longer fasting
      times. Hypoactive emergence was associated with longer postoperative PACU and
      hospital LOSs.

PMID- 23965210
TI  - Analgesia after Cesarean delivery: a retrospective comparison of intrathecal
      hydromorphone and morphine.
AB  - STUDY OBJECTIVE: To compare analgesia and opioid-related side effects of
      intrathecal morphine and intrathecal hydromorphone after elective Cesarean
      delivery. DESIGN: Retrospective, comparative study. SETTING: Labor and delivery
      unit of an academic hospital. PATIENTS: 114 parturients age >= 18 years,
      presenting for elective Cesarean delivery. INTERVENTIONS: Patients who received
      0.04 mg intrathecal hydromorphone were compared to a random sample of patients
      who received 0.1 mg intrathecal morphine for postoperative analgesia.
      MEASUREMENTS: The primary outcome was the presence of any opioid-related
      complication (pruritus, nausea or vomiting, respiratory depression) requiring
      treatment within 24 hours of intrathecal opioid administration. Secondary
      outcomes included total opioid consumption (in oral morphine equivalents) within
      24 hours of intrathecal opioid administration and verbal pain score (0 = none, 10
      = worst) at 4, 8, 12, 18, and 24 hours after intrathecal opioid administration.
      MAIN RESULTS: 38 patients who received intrathecal hydromorphone 0.04 mg were
      compared with 76 patients given 0.1 mg of intrathecal morphine for elective
      Cesarean delivery. No significant differences in demographics were noted between
      groups. There were no statistically significant differences between the
      intrathecal hydromorphone and intrathecal morphine groups in overall frequency of
      opioid-related complications (50% vs. 34.2%; P = 0.11), 24-hour opioid
      consumption (33 mg oral morphine equivalent [OME] vs. 8 mg OME; P = 0.27), or
      pain scores at any time point up to 24 hours. CONCLUSIONS: Overall, analgesia and
      incidence of opioid-related side effects after 0.04 mg of intrathecal
      hydromorphone did not differ statistically from 0.1 mg of intrathecal morphine.

PMID- 23965211
TI  - Anesthetic care of parturients with single ventricle physiology.
AB  - Understanding the management of the parturient with single ventricle physiology
      starts with knowledge of the lesion, the patient's current stage of surgical
      palliation, her current functional status, and the impact of pregnancy and labor
      on her cardiac physiology. A multidisciplinary team approach, described in this
      article, is crucial to a positive outcome. 

PMID- 23965212
TI  - Use of a problem-based learning discussion format to teach anesthesiology
      residents research fundamentals.
AB  - STUDY OBJECTIVE: To present a new research problem-based learning discussion
      (PBLD) conference and to evaluate its effect on residents. DESIGN: Retrospective
      observational study of resident education before and after implementation of a
      research PBLD. SETTING: Large U.S. academic anesthesiology department. SUBJECTS:
      93 anesthesiology residents with research PBLD exposure in the academic year (AY)
      2010 and AY 2011, and 85 residents without research PBLD exposure in AY 2008 and
      AY 2009. MEASUREMENTS: Since AY 2010, a PBLD format has been used to teach
      residents clinical research fundamentals. The annual 90-minute PBLD addressed
      residents' perceived barriers to research and introduced research resources
      available via the Clinical and Translational Science Institute (CTSI). Data
      recorded were: 1) number of residents who made CTSI consultation solicitations as
      a new investigator, and 2) number of new research projects proposed by the
      residents and designed with CTSI consultation. Each outcome was compared between
      the prePBLD group (AY 2008 [n=43] and AY 2009 [n=42]) and the postPBLD group (AY
      2010 [n=43] and AY 2011 [n=50]). MAIN RESULTS: The number of residents who
      consulted the CTSI as new investigators increased from 4 of 85 residents (4.7%)
      in the prePBLD group to 13 of 93 residents (14.0%) in the postPBLD group (P =
      0.042). The number of new research projects for which the residents consulted
      CTSI increased from 10 to 20 (100% increase). CONCLUSION: A PBLD format for
      research education of anesthesiology residents is effective.

PMID- 23965213
TI  - Anesthetic implications of emergent Cesarean section in a parturient with Noonan
      syndrome and bacterial endocarditis.
AB  - Noonan syndrome is a relatively common genetically transmitted disorder
      characterized by facial, cardiac, and musculoskeletal abnormalities. The
      management of a 27 year old woman with Noonan syndrome at 23 weeks' gestation,
      presenting with premature labor, who required an emergent Cesarean section for
      placental abruption, is discussed. In addition to Noonan syndrome, this patient
      had bacterial endocarditis involving the mitral and aortic valves. The anesthetic
      implications of Noonan syndrome and endocarditis during pregnancy are presented. 

PMID- 23965214
TI  - Difficulty in placement of a left-sided double-lumen tube due to aberrant
      tracheobronchial anatomy.
AB  - A rare case of a tracheal bronchus coexisting with a left-shifted carina and an
      acute angle of left main bronchus is presented. A 66 year old man with a history
      of colon cancer was scheduled for right thoracoscopic pericardial window due to
      recurrent pericardial effusion. After induction of anesthesia, the trachea was
      intubated using a 39-French, left-sided double lumen tube (DLT); the DLT was
      positioned with fiberoptic bronchoscopic guidance. Significantly high airway
      pressure was noticed as we initiated one-lung ventilation after the patient was
      positioned in the left lateral decubitus position. While repositioning the DLT,
      we found an aberrant tracheal bronchus. Although multiple attempts were made to
      adjust the DLT so as to achieve lung isolation, we could not place the DLT in the
      appropriate position due to abnormal and distorted anatomy. Lung isolation was
      unsuccessful; both lungs were carefully ventilated with small tidal volumes. 

PMID- 23965215
TI  - Predicting the appropriate uncuffed endotracheal tube size for children: a
      radiograph-based formula versus two age-based formulas.
AB  - STUDY OBJECTIVES: To determine whether a radiograph-based formula using the
      tracheal diameter from a chest radiograph predicted the appropriate endotracheal
      tube (ETT) size in children, and to compare these results with those produced
      using age-based formulas. DESIGN: Retrospective, observational study. SETTING:
      Medical record review. MEASUREMENTS: Data from 537 pediatric patients, aged 3 to
      6 years, who underwent orotracheal intubation with an uncuffed ETT, were randomly
      divided into two datasets: one was used to derive a formula and the other was for
      validation. A radiograph-based formula was obtained by linear regression modeling
      between the tracheal diameter at the seventh cervical vertebra (C7) on chest
      radiography and the appropriate ETT size from the estimation dataset (n=268). The
      appropriate size was defined as the ETT size when air leak pressure was 10 to 30
      cmH2O. The predictive ability of this equation was evaluated using the validation
      dataset (n=269). The primary outcome was the success rate of the prediction. MAIN
      RESULTS: The following radiograph-based formula was obtained: ID = 3 + 0.3 *
      (tracheal diameter at C7). The success rate of the radiograph-based formula was
      57%, which is higher than the 32% (P < 0.001) of the standard age-based formula
      (ID = 4 + age/4) or 43% (P = 0.002) of Penlington's formula (ID = 4.5 + age/4).
      An underestimation of the actual tracheal size occurred in 65% of cases using the
      age-based formulas, but in only 19% with the radiograph-based formula (P <
      0.001). CONCLUSIONS: The radiograph-based formula may be useful for predicting
      the appropriate ETT size in children aged 3 to 6 years.

PMID- 23965216
TI  - A unique case of electrical hazard during anesthesia.

PMID- 23965217
TI  - Immune response to 13-valent pneumococcal conjugate vaccine with a reduced dosing
      schedule.
AB  - BACKGROUND: The 7-valent pneumococcal conjugate vaccine (PCV7) has demonstrated
      effectiveness against pneumococcal illnesses when administered as 3 infant doses
      plus a toddler dose (3+1 schedule) or as an abbreviated schedule of 2 infant
      doses plus a toddler dose (2+1 schedule). The 13-valent pneumococcal conjugate
      vaccine (PCV13) is approved and World Health Organization-prequalified for
      administration in a 2+1 schedule when used as part of routine immunization
      programs. OBJECTIVE: To summarize immunologic responses elicited by PCV13
      administered in a 2+1 schedule and following 2 doses in a 3+1 schedule. METHODS:
      Studies were double-blind, randomized, active-controlled, multicenter studies
      except the Mexico study (open-label, single-arm). In 2+1 studies, PCV13 was
      administered at 2, 4, and 12 (UK) or 3, 5, and 11 (Italy) months. In 3+1 studies
      (Spain and Mexico), assessment was made postdose 2 of the primary series (2, 4,
      and 6 months). The primary immunogenicity endpoint was the proportion of
      participants achieving serotype-specific antipolysaccharide immunoglobulin (Ig)G
      concentrations >= 0.35MUg/mL (i.e., responders) 1 month postdose 2. Pneumococcal
      IgG geometric mean concentrations (GMCs), opsonophagocytic activity (OPA), and
      concomitant vaccine responses were assessed. RESULTS: PCV13 and PCV7 elicited
      comparable immune responses for the 7 common serotypes after 2 infant doses. The
      proportion of PCV13 responders postdose 2 was >85% for most of the 7 common and 6
      additional serotypes, except common serotypes 6B (27.9-81.4%) and 23F (55.8
      77.5%) and additional serotypes 3 (73.8-96.9%) and 6A (79.2-94.4%). Serotypes 6B
      and 23F elicited lower IgG GMCs postdose 2 compared with other serotypes; all
      serotypes demonstrated boosting posttoddler dose. All serotypes demonstrated
      functional activity; >95% of participants achieved OPA levels >= 1:8 postdose 2.
      Concomitant vaccine responses were similar between PCV13 and PCV7 groups.
      CONCLUSION: Immune responses elicited by PCV13 following 2 infant doses support
      transition from PCV7 to PCV13 in countries using a 2+1 schedule.

PMID- 23965218
TI  - Comparison of CRM197, diphtheria toxoid and tetanus toxoid as protein carriers
      for meningococcal glycoconjugate vaccines.
AB  - Glycoconjugate vaccines are among the most effective and safest vaccines ever
      developed. Diphtheria toxoid (DT), tetanus toxoid (TT) and CRM197 have been
      mostly used as protein carriers in licensed vaccines. We evaluated the
      immunogenicity of serogroup A, C, W-135 and Y meningococcal oligosaccharides
      conjugated to CRM197, DT and TT in naive mice. The three carriers were equally
      efficient in inducing an immune response against the carbohydrate moiety in
      immunologically naive mice. The effect of previous exposure to different dosages
      of the carrier protein on the anti-carbohydrate response was studied using
      serogroup A meningococcal (MenA) saccharide conjugates as a model. CRM197 showed
      a strong propensity to positively prime the anti-carbohydrate response elicited
      by its conjugates or those with the antigenically related carrier DT. Conversely
      in any of the tested conditions TT priming did not result in enhancement of the
      anti-carbohydrate response elicited by the corresponding conjugates. Repeated
      exposure of mice to TT or to CRM197 before immunization with the respective MenA
      conjugates resulted in a drastic suppression of the anti-carbohydrate response in
      the case of TT conjugate and only in a slight reduction in the case of CRM197.
      The effect of carrier priming on the anti-MenA response of DT-based conjugates
      varied depending on their carbohydrate to protein ratio. These data may have
      implications for human vaccination since conjugate vaccines are widely used in
      individuals previously immunized with DT and TT carrier proteins. 

PMID- 23965219
TI  - Construction, characterization and preclinical evaluation of MTBVAC, the first
      live-attenuated M. tuberculosis-based vaccine to enter clinical trials.
AB  - The development of a new tuberculosis vaccine is an urgent need due to the
      failure of the current vaccine, BCG, to protect against the respiratory form of
      the disease. MTBVAC is an attenuated Mycobacterium tuberculosis vaccine candidate
      genetically engineered to fulfil the Geneva consensus requirements to enter human
      clinical trials. We selected a M. tuberculosis clinical isolate to generate two
      independent deletions without antibiotic-resistance markers in the genes phoP,
      coding for a transcription factor key for the regulation of M. tuberculosis
      virulence, and fadD26, essential for the synthesis of the complex lipids
      phthiocerol dimycocerosates (DIM), one of the major mycobacterial virulence
      factors. The resultant strain MTBVAC exhibits safety and biodistribution profiles
      similar to BCG and confers superior protection in preclinical studies. These
      features have enabled MTBVAC to be the first live attenuated M. tuberculosis
      vaccine to enter clinical evaluation. 

PMID- 23965220
TI  - Development of a fast-dissolving tablet formulation of a live attenuated
      enterotoxigenic E. coli vaccine candidate.
AB  - Vaccination is considered the most cost-effective approach to preventing
      infectious diseases, yet better formulations and delivery methods for efficient
      distribution and administration of vaccines are needed, especially for low
      resource settings. A fast-dissolving tablet (FDT) that could be packaged in a
      compact stackable blister sheet is a potentially attractive option for
      formulating oral vaccines, since it would minimally impact the cold chain and
      could potentially be administered directly to patients without reconstitution.
      This study focused on using one component of a live attenuated trivalent vaccine
      under development to produce a FDT for the prevention of diarrhea induced by
      enterotoxigenic Escherichia coli (ETEC). Ten formulations were prepared and
      freeze dried to produce FDTs. Three freezing conditions were explored, along with
      different drying and package sealing methods. Physical properties examined
      included structural integrity, dissolution time, moisture content, and glass
      transition temperature. Bacterial viability was tested by assaying for colony
      forming units. The formulation compositions and freeze-drying parameters were
      adjusted in an iterative process to arrive at a promising formulation for the
      ETEC vaccine tablet. This formulation included sucrose and trehalose as
      cryoprotectants; phosphate and glutamate salts as buffers and stabilizers; and
      Natrosol((r)), polyvinylpyrrolidone, and mannitol as binders. The process loss in
      viability during freeze drying was less than 0.3 log 10 (50% recovery) for the
      optimized vaccine tablet formulation. The final tablets were robust,
      disintegrated in less than 10s, and preserved the bacteria at 2-8 degrees C for
      at least 12 months with less than 0.4 log 10 loss (40% recovery) in viability
      during storage. This study indicates that the FDT produced by freeze drying
      directly in a blister sheet could be a practical option for formulating ETEC
      vaccines for oral immunization and help to facilitate delivery of lifesaving
      vaccines, particularly in low-resource settings.

PMID- 23965221
TI  - Risk of invasive pneumococcal disease in children and adults with asthma: a
      systematic review.
AB  - BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommended
      the inclusion of asthma as a high-risk condition that should warrant pneumococcal
      vaccination, but the National Advisory Committee on Immunization (NACI) in Canada
      has not yet done so. We aimed to determine the risk of invasive pneumococcal
      disease (IPD) in patients with asthma. METHODS: We searched Ovid Medline, EMBASE,
      Classic EMBASE, PubMEd and Cochrane for articles published between January 1990
      and February 2013, using the MeSH terms pneumococcal infections/or invasive
      pneumococcal disease and asthma. Google Scholar was used to retrieve articles
      citing the seminal article by Talbot et al. Articles were included if they were
      population-based studies that evaluated the relationship between IPD and asthma.
      Two authors independently assessed all titles and abstracts. All potentially
      relevant articles were retrieved as full text and assessed for inclusion.
      RESULTS: The combined searches yielded 376 articles, which were reviewed by title
      and abstract. At this stage, 330 articles were excluded; 40 articles were
      excluded at the full article review stage - leaving 6 articles. Two additional
      articles were found through Google Scholar. The evidence reviewed consistently
      showed a positive association between asthma and risk of IPD. However, the
      magnitude of this effect was heterogeneous with adjusted odds ratios ranging from
      6.7 (95% CI 1.6-27.3) in adults >18 years to 1.7 (95% CI 0.99-3.0) in individuals
      aged 2-49 with low-risk asthma. CONCLUSION: The positive association between
      asthma and risk of IPD supports the addition of asthma as a high-risk condition
      warranting pneumococcal vaccination. Data on vaccine effectiveness in this
      population is needed.

PMID- 23965222
TI  - Health technology assessments as a mechanism for increased value for money:
      recommendations to the Global Fund.
AB  - The Global Fund is experiencing increased pressure to optimize results and
      improve its impact per dollar spent. It is also in transition from a provider of
      emergency funding, to a long-term, sustainable financing mechanism. This paper
      assesses the efficacy of current Global Fund investment and examines how health
      technology assessments (HTAs) can be used to provide guidance on the relative
      priority of health interventions currently subsidized by the Global Fund. In
      addition, this paper identifies areas where the application of HTAs can exert the
      greatest impact and proposes ways in which this tool could be incorporated, as a
      routine component, into application, decision, implementation, and monitoring and
      evaluation processes. Finally, it addresses the challenges facing the Global Fund
      in realizing the full potential of HTAs. 

PMID- 23965223
TI  - Opioids for chronic non-cancer pain: a protocol for a systematic review of
      randomized controlled trials.
AB  - BACKGROUND: Opioids are prescribed frequently and increasingly for the management
      of chronic non-cancer pain (CNCP). Current systematic reviews have a number of
      limitations, leaving uncertainty with regard to the benefits and harms associated
      with opioid therapy for CNCP. We propose to conduct a systematic review and meta
      analysis to summarize the evidence for using opioids in the treatment of CNCP and
      the risk of associated adverse events. METHODS AND DESIGN: Eligible trials will
      include those that randomly allocate patients with CNCP to treatment with any
      opioid or any non-opioid control group. We will use the guidelines published by
      the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials
      (IMMPACT) to inform the outcomes that we collect and present. We will use the
      Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system
      to evaluate confidence in the evidence on an outcome-by-outcome basis. Teams of
      reviewers will independently and in duplicate assess trial eligibility, abstract
      data, and assess risk of bias among eligible trials. To ensure interpretability
      of our results, we will present risk differences and measures of relative effect
      for all outcomes reported and these will be based on anchor-based minimally
      important clinical differences, when available. We will conduct a priori defined
      subgroup analyses consistent with current best practices. DISCUSSION: Our review
      will evaluate both the effectiveness and the adverse events associated with
      opioid use for CNCP, evaluate confidence in the evidence using the GRADE
      approach, and prioritize patient-important outcomes with a focus on functional
      gains guided by IMMPACT recommendations. Our results will facilitate evidence
      based management of patients with CNCP and identify key areas for future
      research. TRIAL REGISTRATION: Our protocol is registered on PROSPERO
      (CRD42012003023), http://www.crd.york.ac.uk/PROSPERO.

PMID- 23965224
TI  - PrefHer: finally addressing the preferences of her, too.

PMID- 23965225
TI  - Preference for subcutaneous or intravenous administration of trastuzumab in
      patients with HER2-positive early breast cancer (PrefHer): an open-label
      randomised study.
AB  - BACKGROUND: Subcutaneous trastuzumab has shown non-inferior efficacy and a
      similar pharmacokinetic and safety profile when compared with intravenous
      trastuzumab in patients with HER2-positive early breast cancer. We assessed
      patient preference for either subcutaneous or intravenous trastuzumab in the
      international, randomised PrefHer study. METHODS: Eligible patients were women
      aged 18 years or older with HER2-positive, histologically confirmed primary
      invasive breast adenocarcinoma, no evidence of residual, locally recurrent, or
      metastatic disease after completion of surgery and chemotherapy (neoadjuvant or
      adjuvant), an Eastern Cooperative Oncology Group performance status of 0 or 1,
      and a baseline left-ventricular ejection fraction of 55% or more before the first
      dose of trastuzumab. Radiotherapy or hormone therapy was allowed. Patients were
      randomised (randomly permuted blocks of four) to receive four cycles of 600 mg
      fixed-dose subcutaneous adjuvant trastuzumab via a single-use injection device or
      hand-held syringe followed by four cycles of standard intravenous trastuzumab, or
      the reverse sequence. Randomisation was stratified by de-novo versus non-de-novo
      use of intravenous trastuzumab. The primary endpoint was the proportion of
      patients indicating an overall preference for subcutaneous or intravenous
      trastuzumab, assessed by patient interview in the evaluable intention-to-treat
      (ITT) population (patients who completed both interviews and had at least one
      administration of both subcutaneous and intravenous trastuzumab). Data collection
      for PrefHer is ongoing. This study is registered with ClinicalTrials.gov, number
      NCT01401166. FINDINGS: 124 patients were randomly allocated to receive
      subcutaneous followed by intravenous trastuzumab, and 124 to receive the reverse
      sequence. 117 patients in the subcutaneous first group and 119 in the intravenous
      first group were included in the evaluable ITT population. Subcutaneous
      trastuzumab via the single-use injection device was preferred by 216 patients
      (91.5%, 95% CI 87.2-94.7; p<0.0001). Only 16 patients preferred intravenous
      trastuzumab (6.8%, 3.9-10.8), and four had no preference (1.7%, 0.5-4.3).
      Clinician-reported adverse events occurred in 141 of 242 (58%) patients during
      the pooled subcutaneous periods and 105 of 241 (44%) patients during the pooled
      intravenous periods; seven (3%) and five (2%) were grade 3, no patients had a
      grade 4 or 5 event. The most common grade 3 adverse event was influenza (two
      [0.8%] patients). INTERPRETATION: Patient preference and safety results from
      PrefHer, combined with the known non-inferior efficacy and pharmacokinetic and
      safety profile data, suggest that a fixed dose of 600 mg trastuzumab administered
      subcutaneously every 3 weeks is a validated, well tolerated treatment option for
      HER2-positive breast cancer, and is the preferred treatment of patients.

PMID- 23965226
TI  - Dissimilarities in the metabolism of antiretroviral drugs used in HIV pre
      exposure prophylaxis in colon and vagina tissues.
AB  - Attempts to prevent HIV infection through pre-exposure prophylaxis (PrEP) include
      topical application of anti-HIV drugs to the mucosal sites of infection; however,
      a potential role for local drug metabolizing enzymes in modulating the exposure
      of the mucosal tissues to these drugs has yet to be explored. Here we present the
      first report that enzymes belonging to the cytochrome P450 (CYP) and UDP
      glucuronosyltransferase (UGT) families of drug metabolizing enzymes are expressed
      and active in vaginal and colorectal tissue using biopsies collected from healthy
      volunteers. In doing so, we discovered that dapivirine and maraviroc, a non
      nucleoside reverse transcriptase inhibitor and an entry inhibitor currently in
      development as microbicides for HIV PrEP, are differentially metabolized in
      colorectal tissue and vaginal tissue. Taken together, these data should help to
      guide the optimization of small molecules being developed for HIV PrEP. 

PMID- 23965227
TI  - Lessons learned from the conduct of a multisite cluster randomized practical
      trial of decision aids in rural and suburban primary care practices.
AB  - BACKGROUND: The decision aids for diabetes (DAD) trial explored the feasibility
      of testing the effectiveness of decision aids (DAs) about coronary prevention and
      diabetes medications in community-based primary care practices, including rural
      clinics that care for patients with type 2 diabetes. METHODS: As originally
      designed, we invited clinicians in eight practices to participate in the trial,
      reviewed the patient panel of clinicians who accepted our invitation for
      potentially eligible patients, and contacted these patients by phone, enrolling
      those who accepted our invitation. As enrollment failed to meet targets, we
      recruited four new practices. After discussing the study with the clinicians and
      receiving their support, we reviewed all clinic panels for potentially eligible
      patients. Clinicians were approached to confirm participation and patient
      eligibility, and patients were approached before their visit to provide written
      informed consent. This in-clinic approach required study coordinators to travel
      and stay longer at the clinics as well as to screen more patient records for
      eligibility. The in-clinic approach was associated with better recruitment rates,
      lower patient retention and outcome completion rates, and a better intervention
      effect. RESULTS: We drew four lessons: 1) difficulties identifying potentially
      eligible patients threaten the viability of practical trials of DAs; 2) to
      improve the recruitment yield, recruit clinicians and patients for the study at
      the clinic, just before their visit; 3) approaches that improve recruitment may
      be associated with reduced retention and survey response; and 4) procedures that
      involve working closely with the practice may improve recruitment and may also
      affect the quality of the implementation of the interventions. CONCLUSION:
      Success in practice-based trials in usual primary care including rural clinics
      may require the smallest possible research footprint on the practice while
      implementing a streamlined protocol favoring in-clinic, in-person interactions
      with clinicians and patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01029288.

PMID- 23965228
TI  - Transcranial doppler assessment of cerebral perfusion in critically ill septic
      patients: a pilot study.
AB  - BACKGROUND: The aim of this study is to evaluate the feasibility and efficacy of
      Transcranial Doppler (TCD) in assessing cerebral perfusion changes in septic
      patients. METHODS: Using TCD, we measured the mean velocity in the middle
      cerebral artery (VmMCA, cm/sec) and calculated the pulsatility index (PI),
      resistance index (RI) and cerebral blood flow index (CBFi = 10*MAP/1.47(PI)) on
      the first day of patients' admission or on the first day of sepsis development;
      measurements were repeated on the second day. Sepsis was defined according to
      standard criteria. RESULTS: Forty-one patients without any known neurologic
      deficit treated in our 24-bed Critical Care Unit were assessed (Sepsis Group =
      20, Control Group = 21). Examination was feasible in 91% of septic and 85% of non
      septic patients (p = 0.89). No difference was found between the two groups in
      mean age, mean arterial pressure (MAP) or APACHE II score. The pCO2 values were
      higher in septic patients (46 +/- 12 vs. 39 +/- 4 mmHg p < 0.01). No
      statistically significant higher values of VmMCA were found in septic patients
      (110 +/- 34 cm/sec vs. 99 +/- 28 cm/sec p = 0.17). Higher values of PI and RI
      were found in septic patients (1.15 +/- 0.25 vs. 0.98 +/- 0.16 p < 0.01, 0.64 +/-
      0.08 vs. 0.59 +/- 0.06 p < 0.01, respectively). No statistically significant
      lower values of CBFi were found in septic patients (497 +/- 116 vs. 548 +/- 110 p
      = 0.06). CONCLUSIONS: Our results suggest cerebral vasoconstriction in septic
      compared to non-septic patients. TCD is an efficient and feasible exam to
      evaluate changes in cerebral perfusion during sepsis.

PMID- 23965229
TI  - Ejaculatory ducts opening into accessory urethral channel with hypospadias and
      absent verumontanum: a rare association.
AB  - Ejaculatory ducts draining into accessory urethral channel opening into perineum
      is rare. This is a case report of a 27-year-old male who had hypospadias surgery
      at 3 years of age, presenting with discharge of semen through the perineal
      opening from adolescence. Cystoscopy and dye study showed that it was a short
      channel communicating with both ejaculatory ducts. Cystoscopy of the native
      urethra revealed that the vermontanum had not developed. The mucous lined
      accessory urethra was anastomosed to the bulbar urethra. Urethrogram done after
      one year showed that the accessory urethra was draining well into the bulbar
      urethra. Such type of accessory urethral channel communicating with ejaculatory
      ducts and associated with hypospadias and absent vermontanum has not been
      reported so far. 

PMID- 23965230
TI  - An audit of holotranscobalamin ("Active" B12) and methylmalonic acid assays for
      the assessment of vitamin B12 status: application in a mixed patient population.
AB  - BACKGROUND: Vitamin B12 insufficiency/deficiency is common in mixed patient
      populations. However there is no single marker which can reliably diagnose B12
      insufficiency/deficiency. Elevated concentrations of methylmalonic acid (MMA) are
      considered the most representative marker of metabolic vitamin B12 insufficiency,
      but poor assay availability limits clinical utility. Low concentrations of serum
      vitamin B12 are often used to assess vitamin B12 status but this approach
      generates a high rate of false negative results. Emerging evidence indicates that
      holotranscobalamin (holoTC) may be a more reliable indicator of vitamin B12
      status. AIMS AND METHODS: We substituted serum vitamin B12 measurement with
      holoTC, supported by MMA in patients referred for assessment of vitamin B12
      status. A service evaluation was undertaken of the pattern of MMA values obtained
      for patients with holoTC 25-50 pmol/L (an indeterminate result). MMA cut-offs of
      280 and 360 nmol/L were applied for patients <= 65 or >65 years respectively.
      RESULTS: A total of 4,175 consecutive patients were investigated and MMA was
      analysed for 19% of patients. The incidence of elevated MMA was 41% (holoTC, 25
      29 pmol/L), 32% (30-34 pmol/L), 33% (35-39 pmol/L), 30% (40-44 pmol/L), and 26%
      (45-50 pmol/L). CONCLUSIONS: Our results indicate that in the clinical setting a
      holoTC between 25 and 50 pmol/L is a poor predictor for the concentration of MMA
      provided the goal is to identify patients with MMA values above the limits used
      in the present study. Further studies are needed to evaluate to what extent
      holoTC <25 and >50 pmol/L reflect circulatory MMA concentrations.

PMID- 23965231
TI  - SCORE and REGICOR function charts underestimate the cardiovascular risk in
      Spanish patients with rheumatoid arthritis.
AB  - INTRODUCTION: Our objective was to determine which one of the two function charts
      available in Spain to calculate cardiovascular (CV) risk, Systematic COronary
      Risk Evaluation (SCORE) or Framingham-REgistre GIroni del COR (REGICOR), should
      be used in patients with rheumatoid arthritis (RA). METHODS: A series of RA
      patients seen over a one-year period without history of CV events were assessed.
      SCORE, REGICOR, modified (m)SCORE and mREGICOR according to the European League
      Against Rheumatism (EULAR) recommendations were applied. Carotid ultrasonography
      (US) was performed. Carotid intima-media thickness (cIMT) > 0.90 mm and/or
      carotid plaques were used as the gold standard test for severe subclinical
      atherosclerosis and high CV risk (US+). The area under the receiver operating
      curves (AUC) for the predicted risk for mSCORE and mREGICOR were calculated
      according to the presence of severe carotid US findings (US+). RESULTS: We
      included 370 patients (80% women; mean age 58.9 +/- 13.7 years); 36% had disease
      duration of 10 years or more; rheumatoid factor (RF) and/or anticyclic
      citrullinated peptide (anti-CCP) were positive in 68%; and 17% had extra
      articular manifestations. The EULAR multiplier factor was used in 122 (33%) of
      the patients. The mSCORE was 2.16 +/- 2.49% and the mREGICOR 4.36 +/- 3.46%.
      Regarding US results, 196 (53%) patients were US+. The AUC mSCORE was 0.798 (CI
      95%: 0.752 to 0.844) and AUC mREGICOR 0.741 (95% CI; 0.691 to 0.792). However,
      mSCORE and mREGICOR failed to identify 88% and 91% of US+ patients. More than 50%
      of patients with mSCORE >=1% or mREGICOR >1% were US+. CONCLUSIONS: Neither of
      these two function charts was useful in estimating CV risk in Spanish RA
      patients.

PMID- 23965232
TI  - TP53 mutations are common in all subtypes of epithelial ovarian cancer and occur
      concomitantly with KRAS mutations in the mucinous type.
AB  - AIMS: Epithelial ovarian cancer (EOC) can be classified into four major types
      (serous, endometrioid, clear cell, mucinous). The prevalence of driver gene
      mutations in the different subtypes is controversial. High-grade serous
      carcinomas show frequent TP53 mutations, whereas KRAS and BRAF mutations are less
      common. In non-serous EOC, the relevance of these gene mutations remains to be
      elucidated. METHODS: We investigated 142 formalin-fixed, paraffin-embedded EOC,
      including serous (n=63), endometrioid (n=29), clear cell (n=25), mucinous (n=14),
      and others (n=11) for mutations in TP53 exons 5-8, KRAS exons 2 and 3, and BRAF
      exon 15 by pyro-sequencing using the GS Junior 454 platform. The mutational
      status was correlated with clinicopathological features and patient overall
      survival. RESULTS: We identified mutations in the coding region of TP53 in 51.4%
      (73/142), and of KRAS in 9.9% (14/142) but not of BRAF. TP53 mutations occurred
      frequently not only in high-grade serous carcinomas (58.7%), but also in mucinous
      (57%) and clear cell EOC (52%). TP53 mutations were associated with high-grade
      carcinomas (p=0.014), advanced FIGO stage (p=0.001), intraoperative residual
      disease >1cm (p=0.004), as well as poor overall survival (p=0.002). KRAS
      mutations were mainly identified in mucinous EOC (57%) and were concomitantly
      with TP53 mutations in five mucinous carcinomas (36%). CONCLUSIONS: TP53 gene
      driver mutations are a common feature of all advanced ovarian cancer subtypes,
      whereas BRAF mutations seem to be a rare event in EOC. KRAS mutations with
      synchronous TP53 mutations occur predominantly in low-grade mucinous carcinomas,
      suggesting a specific molecular background of this ovarian cancer type.

PMID- 23965233
TI  - Age-related changes of fibroblast density in the human periodontal ligament.
AB  - OBJECTIVE: Recently, research has focused intensely on age-related tissue
      changes, not only in the field of dermatology but also in dental sciences.
      Although many new insights into age-related morphological, ultrastructural and
      biochemical changes in the periodontal ligament tissue have been gained, the
      basic question of whether there is a quantitative change in cell number remains
      unanswered or, at least to date, unpublished. Thus, the aim of this study was to
      detect age-related changes of the periodontal ligament regarding fibroblast
      density. MATERIAL AND METHODS: 33 lateral tooth-bearing segments of the maxilla
      were obtained from deceased human individuals of different age, ranging from 7 to
      63 years. The buccal segment of the periodontal ligament of the mesiobuccal root
      of the first maxillary molar was evaluated histomorphometrically to obtain the
      fibroblast density. RESULTS: The results clearly indicate a steady and
      statistically significant decline of fibroblast number with age. CONCLUSION: It
      may be concluded that fibroblast density in the physiological human periodontal
      ligament tissue decreases with age, thus causing an initial delay in
      physiological, pathological or externally induced processes that require
      remodeling of the periodontal ligament, e.g. traumatic occlusion or orthodontic
      tooth movement. It may be assumed that an orthodontic tooth movement in elderly
      patients requires more time in the initial treatment phase and should be done
      with lighter forces.

PMID- 23965234
TI  - Investigating the interaction between heart rate variability and sleep EEG using
      nonlinear algorithms.
AB  - BACKGROUND: The multi-mode modulation is a key feature of sleep EEG. And the
      short-term fractal property reflects the sympathovagal modulation of heart rate
      variability (HRV). The properties of EEG and HRV strongly correlated with sleep
      status and are interesting in clinic diagnosis. NEW METHOD: 19 healthy female
      subjects were included for over-night standard polysomnographic study. Hilbert
      Huang transform (HHT) was used to characterize the temporal features of slow- and
      fast-wave oscillations decomposed from sleep EEG at different stages. Masking
      signals were used for solving the mode-mixing problem in HHT. On the other hand,
      detrended fluctuation analysis (DFA) was used to assess short-term property of
      HRV denoted as DFA alpha1, which reflects the temporal activity of autonomic
      nerve system (ANS). Thus, the dynamic interaction between sleep EEG and HRV can
      be examined through the relationship between the features of sleep EEG and DFA
      alpha1 of HRV. RESULTS: The frequency feature of sleep EEG serves as a good
      indicator for the depth of sleep during non-rapid eye movement (NREM) sleep, and
      amplitude feature of fast-wave oscillation is a good index for distinguishing
      rapid eye movement (REM) from NREM sleep. COMPARISON WITH EXISTING METHOD: The
      relationship between DFA alpha1 of HRV and the mean amplitude of fast-wave
      oscillation of sleep EEG affirmed with Pearson correlation coefficient is more
      significant than the correlation verified by the traditional spectral analysis.
      CONCLUSION: The dynamic properties of sleep EEG and HRV derived by EMD and DFA
      represent important features for cortex and ANS activities during sleep.

PMID- 23965235
TI  - Hypoxia promotes redifferentiation and suppresses markers of hypertrophy and
      degeneration in both healthy and osteoarthritic chondrocytes.
AB  - INTRODUCTION: Hypoxia is considered to be a positive influence on the healthy
      chondrocyte phenotype and cartilage matrix formation. However, hypoxia-inducible
      factors (HIFs) have been implicated in the pathogenesis of osteoarthritis (OA).
      Thus, we assessed whether healthy and OA chondrocytes have distinct responses to
      oxygen, particularly with regard to hypertrophy and degradation during
      redifferentiation. METHODS: Monolayer-expanded healthy and OA chondrocytes were
      redifferentiated for 14 days in pellet cultures under standard (20% oxygen) or
      hypoxic (2% oxygen) conditions. Cartilage matrix gene expression, matrix quality
      and quantity, degradative enzyme expression and HIF expression were measured.
      RESULTS: In hypoxia, both healthy and OA chondrocytes had higher human collagen
      type II, alpha1 gene (COL2A1), and aggrecan (ACAN) expression and sulfated
      glycosaminoglycan (sGAG) accumulation, concomitant with lower human collagen type
      X, alpha1 gene (COL10A1), and human collagen type I, alpha1 gene (COL1A1),
      expression and collagen I extracellular accumulation. OA chondrocytes had
      significantly lower sGAGs/DNA than healthy chondrocytes, but only in high oxygen
      conditions. Hypoxia also caused significantly greater sGAG retention and
      hyaluronic acid synthase 2 (HAS2) expression by OA chondrocytes. Both healthy and
      OA chondrocytes had significantly lower expression of matrix metalloproteinases
      (MMPs) MMP1, MMP2, MMP3 and MMP13 in hypoxia and less active MMP2 enzyme,
      consistent with lower MMP14 expression. However, aggrecanase (ADAMTS4 and
      ADAMTS5) expression was significantly lowered by hypoxia only in healthy cells,
      and COL10A1 and MMP13 remained significantly higher in OA chondrocytes than in
      healthy chondrocytes in hypoxic conditions. HIF-1alpha and HIF-2alpha had similar
      expression profiles in healthy and OA cells, increasing to maximal levels early
      in hypoxia and decreasing over time. CONCLUSIONS: Hypoxic culture of human
      chondrocytes has long been acknowledged to result in increased matrix
      accumulation, but still little is known of its effects on catabolism. We show
      herein that the increased expression of matrix proteins, combined with decreased
      expression of numerous degradative enzymes by hypoxia, minimizes but does not
      abolish differences between redifferentiated healthy and OA chondrocytes. Hypoxia
      induced HIF expression is associated with hypertrophic marker and degradative
      enzyme downregulation and increased measures of redifferentiation in both healthy
      and OA chondrocytes. Therefore, though HIFs may be involved in the pathogenesis
      of OA, conditions that promote HIF expression in vitro promote matrix
      accumulation and decrease degradation and hypertrophy, even in cells from OA
      joints.

PMID- 23965237
TI  - [The electronic health record: computerised provider order entry and the
      electronic instruction document as new functionalities].
AB  - An electronic health record (EHR) should provide 4 key functionalities: (a)
      documenting patient data; (b) facilitating computerised provider order entry; (c)
      displaying the results of diagnostic research; and (d) providing support for
      healthcare providers in the clinical decision-making process.- Computerised
      provider order entry into the EHR enables the electronic receipt and transfer of
      orders to ancillary departments, which can take the place of handwritten orders.-
      By classifying the computer provider order entries according to disorders,
      digital care pathways can be created. Such care pathways could result in faster
      and improved diagnostics.- Communicating by means of an electronic instruction
      document that is linked to a computerised provider order entry facilitates the
      provision of healthcare in a safer, more efficient and auditable manner.- The
      implementation of a full-scale EHR has been delayed as a result of economic,
      technical and legal barriers, as well as some resistance by physicians.

PMID- 23965238
TI  - [Evaluating individual doctors in the IFMS programme].
AB  - The 'Individueel functioneren medisch specialisten' (Individual Functioning of
      Medical Specialists, IFMS) programme is a formative evaluation tool.- The aim of
      the IFMS programme is to consolidate good practices and to ameliorate those less
      desirable. - It is an integral system that takes the complexity of the medical
      profession, the physician as an individual and the expectations and demands from
      the individual's surroundings into account. - The IFMS programme uses the
      physician's intrinsic motivation and individual responsibility as its starting
      points. - The programme's features include maintaining a portfolio and acquiring
      feedback from the surroundings which are then used as a foundation for a personal
      discussion with a trained communicator.- The outcome of this method results in a
      physician who is and remains conscious of the need to deliver high-quality care,
      taking his or her personal aspirations and demands of the work setting into
      account.

PMID- 23965236
TI  - The MOnitoring Resynchronization dEvices and CARdiac patiEnts (MORE-CARE)
      randomized controlled trial: phase 1 results on dynamics of early intervention
      with remote monitoring.
AB  - BACKGROUND: Remote monitoring (RM) in patients with advanced heart failure and
      cardiac resynchronization therapy defibrillators (CRT-D) may reduce delays in
      clinical decisions by transmitting automatic alerts. However, this strategy has
      never been tested specifically in this patient population, with alerts for lung
      fluid overload, and in a European setting. OBJECTIVE: The main objective of Phase
      1 (presented here) is to evaluate if RM strategy is able to reduce time from
      device-detected events to clinical decisions. METHODS: In this multicenter
      randomized controlled trial, patients with moderate to severe heart failure
      implanted with CRT-D devices were randomized to a Remote group (with remote
      follow-up and wireless automatic alerts) or to a Control group (with standard
      follow-up without alerts). The primary endpoint of Phase 1 was the delay between
      an alert event and clinical decisions related to the event in the first 154
      enrolled patients followed for 1 year. RESULTS: The median delay from device
      detected events to clinical decisions was considerably shorter in the Remote
      group compared to the Control group: 2 (25(th)-75(th) percentile, 1-4) days vs 29
      (25(th)-75(th) percentile, 3-51) days respectively, P=.004. In-hospital visits
      were reduced in the Remote group (2.0 visits/patient/year vs 3.2
      visits/patient/year in the Control group, 37.5% relative reduction, P<.001).
      Automatic alerts were successfully transmitted in 93% of events occurring outside
      the hospital in the Remote group. The annual rate of all-cause hospitalizations
      per patient did not differ between the two groups (P=.65). CONCLUSIONS: RM in CRT
      D patients with advanced heart failure allows physicians to promptly react to
      clinically relevant automatic alerts and significantly reduces the burden of in
      hospital visits. TRIAL REGISTRATION: Clinicaltrials.gov NCT00885677;
      http://clinicaltrials.gov/show/NCT00885677 (Archived by WebCite at
      http://www.webcitation.org/6IkcCJ7NF).

PMID- 23965239
TI  - [Antihypertensives: better evenings than mornings].
AB  - In a reasonably large proportion of patients who take antihypertensive drugs (10
      30%), hypertension appears to be therapy resistant; even the use of three
      antihypertensives does not lower the blood pressure sufficiently. The average
      nocturnal blood pressure is a better predictor of cardiovascular events than
      blood pressure measured during the day. Antihypertensives have a stronger effect
      on nocturnal blood pressure when taken in the evening rather than in the morning.
      The exact mechanism of this has not yet been unravelled, but randomised, non
      blinded studies suggest that this so-called chronotherapy does indeed lower
      cardiovascular risk in certain groups. The authors regard this as a promising
      strategy for patients with therapy-resistant hypertension in whom a nocturnal
      blood pressure dip does not occur. 

PMID- 23965240
TI  - [An occult fracture of the capitate bone].
AB  - BACKGROUND: Evaluating patients with wrist injuries is diagnostically
      challenging. Physical examination alone is not sufficient for establishing a
      diagnosis and fractures of the wrist region are not always visible on x-rays.
      CASE DESCRIPTION: In this article, we present a case of a patient who had
      sustained trauma to the wrist and was taken care of at the emergency department.
      The mechanism of trauma and clinical findings strongly indicated a fracture of
      the scaphoid bone. No abnormality was visible on x-rays; the fracture was treated
      by casting nonetheless. On a CT scan performed later, there indeed appear to be a
      non-dislocated fracture of the capitate bone present. The diagnosis was confirmed
      by bone scintigraphy a few days later. The patient recovered without
      complications. CONCLUSION: Fractures of the capitate bone are serious carpal
      injuries that must be treated as aggressively as fractures of the scaphoid bone.
      Conventional radiological examinations cannot rule out a fracture of the wrist;
      if doubt persists, readily accessible imaging techniques (such as CT or MRI)
      should be conducted.

PMID- 23965241
TI  - [Paraneoplastic phenomena in patients with a thymoma].
AB  - A thymoma arises from the epithelial cells of the thymus. Local tumour growth may
      cause symptoms like coughing, dyspnoea or chest pain. Paraneoplastic phenomena
      can also occur in patients with a thymoma; myasthenia gravis is a well-known
      example. Other neurological, dermatological, cardiological and haematological
      disorders are not always recognised as being paraneoplastic phenomena. There is
      no clear relationship between tumour activity and the clinical course of
      paraneoplastic phenomena. The three cases in this article illustrate how the
      clinical presentation of these phenomena can vary. 

PMID- 23965242
TI  - [A woman with an abnormality of the palate].
AB  - A 75-year-old woman was seen at the ENT department because of a bleeding tumor on
      the hard palate. The abnormality mimicked both clinically and histopathologically
      a malignant salivary gland tumor, but after excision it was diagnosed as
      necrotizing sialometaplasia. Clinicians should be aware of this rare and easily
      misdiagnosed benign disease, in order to avoid unnecessary treatment. 

PMID- 23965243
TI  - [When the health care inspectorate closes the operating theatres: a case study].
AB  - BACKGROUND: The topic of 'quality of care' is subject to intense interest from
      the media, the public and the government. One of the key roles of the Dutch
      Health Care Inspectorate (IGZ) is the supervision and monitoring of quality of
      care. When the IGZ pays a visit, this generally has many consequences for the
      hospital concerned. CASE STUDY: Following an unannounced inspection of a
      hospital, the IGZ closed the operating department due to shortcomings in the
      quality of care. The IGZ and the hospital proved to have different ideas
      concerning the norms of quality. Using a theoretical framework we have tried to
      provide some insight into the consequences of this situation. CONCLUSION: A
      hospital comprises a number of different domains each with its own value system
      (market, governmental and political, societal, medical profession). To prevent
      these differences standing in the way of good care, we advise all parties to look
      outside their own domain in order to overcome the boundaries and connect to other
      domains and value systems.

PMID- 23965244
TI  - [Improved hospital care for elderly patients: guidance on vulnerability and goal
      assessment].
AB  - Hospital care is highly disease-focused, tending towards further specialisation,
      and largely driven by technological innovations. Frail elderly, however, are an
      important and rapidly growing group of patients that is not best cared for in
      such a clinical environment. Case histories and the description of outcomes of an
      innovative programme called 'CareWell Primary Care' reveal that triage based on
      frailty and a global geriatric assessment of frail patients which is linked to
      goal-oriented hospital care and shared decision-making are the cornerstones of
      much needed improvement in delivering effective, safe, and sustainable hospital
      care to our ageing population. 

PMID- 23965245
TI  - [Preeclampsia as cardiovascular risk factor].
AB  - Cardiovascular diseases (CVD) are the primary cause of death in women. Guidelines
      for identifying high-risk individuals have been developed, e.g. the Dutch
      Guideline on Cardiovascular Risk Management. In the most recent version of this
      guideline, diabetes mellitus (DM) and rheumatoid arthritis (RA) are cited as
      cardiovascular risk factors; therefore, individuals with these conditions are
      identified as being at high risk. As with DM and RA, there is strong evidence
      that the experience of having a hypertensive disorder during pregnancy is a
      cardiovascular risk factor. This is particularly the case for early preeclampsia,
      which constitutes a 7-fold increased risk of ischemic heart disease. However, in
      the Netherlands, there are no guidelines and there is no consensus on how to
      screen or treat these women. Trial evidence is therefore urgently needed to
      substantiate the value of cardiovascular risk management for those women with a
      history of hypertension during pregnancy. 

PMID- 23965246
TI  - [A girl with brown skin abnormalities of the neck].
AB  - A 12-year-old girl visited the dermatologist with asymptomatic brown skin
      abnormalities of the neck and the umbilicus. Dermatologic examination showed
      multiple reticulate brown patches at both sites. All dermal abnormalities
      disappeared after firm wiping with 70% isopropyl alcohol, revealing the diagnosis
      'pheoderma'. 

PMID- 23965247
TI  - [Treatment of colorectal liver metastasis at a regional hospital versus a
      university medical centre].
AB  - OBJECTIVE: To evaluate the results of this type of liver surgery performed at a
      specialised regional hospital in comparison with the operation performed at a
      university medical centre (UMC). DESIGN: Prospective study at 2 hospitals.
      METHODS: All patients with colorectal liver metastasis who had undergone a
      partial liver resection and/or radiofrequency ablation (RFA) at Amphia Hospital
      or at the Academic Medical Centre - University of Amsterdam (AMC) from January
      2005-June 2011 were included. Data on patient characteristics, type of operation,
      pathology results and (disease-free) survival were collected. The primary outcome
      measures were surgical complications and survival. RESULTS: A total of 232
      patients were included. No difference in patient characteristics between centres
      was identified. At the AMC, 121 patients (98.4%) had undergone a resection; 6 in
      combination with RFA. Two patients (1.6%) had only undergone RFA. At Amphia
      Hospital, 85 patients (78%) had undergone a resection; 30 in combination with
      RFA. In 24 patients (22%), only RFA was performed. There was significant
      difference in the type of treatment (p < 0.01). Not significantly different
      between centres were the average lengths of hospital stays, surgical
      complications and recurrence rates. After resection, no significant differences
      in the 1- and 3-year (disease-free) survival rates were found between the
      centres. At Amphia Hospital, the overall survival at 1, 3 and 5 years was 86, 47
      and 29%, respectively. These rates were significantly better at AMC with 91, 78
      and 53%, respectively (p < 0.05). The difference in (disease-free) survival for
      the entire group of patients can be explained by the more frequent performance of
      RFA at Amphia Hospital. CONCLUSIONS: Postoperative morbidity, mortality and
      survival rates after liver surgery obtained from a specialised regional hospital
      are similar to results obtained from a UMC.

PMID- 23965248
TI  - [The measles are here again].
AB  - Since the vaccination of Dutch children against the measles through the National
      Immunisation Programme started in 1976, the incidence of measles has greatly
      decreased. Local epidemics do still occur, however; these are largely confined to
      minority groups of orthodox Protestants who object to vaccination on religious
      grounds. A local epidemic of the measles has been developing in the Netherlands
      since May of this year, predominantly within unvaccinated groups where the highly
      contagious virus can easily spread. We describe an unvaccinated 10-year-old boy
      with an uncomplicated case of the measles and an unvaccinated 9-year-old boy who
      developed encephalitis as a complication of the measles. From the waning of
      maternal antibodies until the first regular vaccination and where herd immunity
      is lacking, children are at risk of the measles. For this reason, an extra (age <
      12 months) or early (12-14 months) vaccination is being offered during the
      current epidemic for all children aged 6 to 14 months who live in areas with low
      (< 90%) vaccination coverage. 

PMID- 23965249
TI  - A randomized controlled trial on preweaning morbidity, growth and mortality in
      Holstein heifers fed a lacteal-derived colostrum replacer or pooled maternal
      colostrum.
AB  - BACKGROUND: The objective of this randomized controlled trial was to determine
      the effect of feeding a commercial lacteal-derived colostrum replacer (CR) or
      pooled maternal colostrum (MC) on preweaning morbidity, growth and mortality in
      Holstein heifer calves. A total of 568 calves were randomly assigned to be fed
      either 3.8 L of pooled MC or two doses (200 g IgG) of a CR. Calves were monitored
      daily for preweaning morbidity until weaning at 60 d old. Birth and weaning
      weights were measured to estimate growth rates. RESULTS: Calves fed CR were
      significantly less likely to be affected with a diarrhea event (OR = 0.58; 95%
      CI, 0.38 to 0.88; P value = 0.011) and had a higher rate of daily weight gain
      (0.051 kg/day; 95% CI, 0.03 to 0.08; P value <0.001) compared to calves fed
      pooled MC. Use of lacteal-derived colostrum replacer was not significantly
      associated with respiratory disease (OR = 1.01; 95% CI 0.67 to 1.51; P value =
      0.974 ), omphalitis (OR = 0.93; 95% CI 0.06 to 14.86; P value = 0.956), or
      mortality (HR = 0.71; 95% CI 0.27 to 1.92; P value = 0.505) in the study calves.
      CONCLUSIONS: The lacteal-derived CR fed at the study dose was a viable colostrum
      alternative in the event of poor quality pooled MC for the prevention of
      preweaning diarrhea and resulted in higher growth rates in comparison to calves
      fed pooled MC in the study herd.

PMID- 23965250
TI  - Isolation of alpaca anti-idiotypic heavy-chain single-domain antibody for the
      aflatoxin immunoassay.
AB  - Anti-idiotypic antibodies recognize the antigenic determinants of an antibody,
      thus they can be used as surrogate antigens. Single-domain antibodies from camlid
      heavy-chain antibodies with the benefit features of small size, thermostability,
      and ease in expression, are leading candidates to produce anti-idiotypic
      antibodies. In this work, we constructed an antibody phage library from the mRNA
      of an alpaca immunized with an antiaflatoxin monoclonal antibody (mAb) 1C11.
      Three anti-idiotypic VHH antibodies were isolated and applied to immunoassay
      toward aflatoxin as a coating antigen. The best immunoassay developed with one of
      these VHH antibodies shows an IC50 of 0.16 ng/mL toward aflatoxin B1 and cross
      reactivity toward aflatoxin B2, G1, and G2 of 90.4%, 54.4%, and 37.7%,
      respectively. The VHH-based immunoassay was successfully applied to the analysis
      of peanuts, corn, and rice, which are the predominant commodities regularly
      contaminated by aflatoxins. A good correlation (r(2) = 0.89) was found between
      the data obtained from the conventional ELISA and the ELISA based on a VHH
      coating antigen for the analysis of aflatoxins in peanuts and feedstuff. The use
      of biotechnology in developing the surrogate, the absence of standard aflatoxin
      and organic solvents in the synthesis procedures, and the reproducibility of the
      VHH antibody makes it an ideal strategy for replacing conventional synthesized
      antigens. 

PMID- 23965251
TI  - Online solid phase extraction liquid chromatography tandem mass spectrometry (SPE
      LC-MS/MS) method for the determination of sucralose in reclaimed and drinking
      waters and its photo degradation in natural waters from South Florida.
AB  - BACKGROUND: Sucralose has gained popularity as a low calorie artificial sweetener
      worldwide. Due to its high stability and persistence, sucralose has shown
      widespread occurrence in environmental waters, at concentrations that could reach
      up to several MUg/L. Previous studies have used time consuming sample preparation
      methods (offline solid phase extraction/derivatization) or methods with rather
      high detection limits (direct injection) for sucralose analysis. This study
      described a faster and sensitive analytical method for the determination of
      sucralose in environmental samples. RESULTS: An online SPE-LC-MS/MS method was
      developed, being capable to quantify sucralose in 12 minutes using only 10 mL of
      sample, with method detection limits (MDLs) of 4.5 ng/L, 8.5 ng/L and 45 ng/L for
      deionized water, drinking and reclaimed waters (1:10 diluted with deionized
      water), respectively. Sucralose was detected in 82% of the reclaimed water
      samples at concentrations reaching up to 18 MUg/L. The monthly average for a
      period of one year was 9.1 +/- 2.9 MUg/L. The calculated mass loads per capita of
      sucralose discharged through WWTP effluents based on the concentrations detected
      in wastewaters in the U. S. is 5.0 mg/day/person. As expected, the concentrations
      observed in drinking water were much lower but still relevant reaching as high as
      465 ng/L. In order to evaluate the stability of sucralose, photodegradation
      experiments were performed in natural waters. Significant photodegradation of
      sucralose was observed only in freshwater at 254 nm. Minimal degradation (<20%)
      was observed for all matrices under more natural conditions (350 nm or solar
      simulator). The only photolysis product of sucralose identified by high
      resolution mass spectrometry was a de-chlorinated molecule at m/z 362.0535, with
      molecular formula C12H20Cl2O8. CONCLUSIONS: Online SPE LC-APCI/MS/MS developed in
      the study was applied to more than 100 environmental samples. Sucralose was
      frequently detected (>80%) indicating that the conventional treatment process
      employed in the sewage treatment plants is not efficient for its removal.
      Detection of sucralose in drinking waters suggests potential contamination of
      surface and ground waters sources with anthropogenic wastewater streams. Its high
      resistance to photodegradation, minimal sorption and high solubility indicate
      that sucralose could be a good tracer of anthropogenic wastewater intrusion into
      the environment.

PMID- 23965252
TI  - Development of a strand-specific real-time qRT-PCR for the accurate detection and
      quantitation of West Nile virus RNA.
AB  - Studying the tropism and replication kinetics of West Nile virus (WNV) in
      different cell types in vitro and in tissues in animal models is important for
      understanding its pathogenesis. As detection of the negative strand viral RNA is
      a more reliable indicator of active replication for single-stranded positive
      sense RNA viruses, the specificity of qRT-PCR assays currently used for the
      detection of WNV positive and negative strand RNA was reassessed. It was shown
      that self- and falsely-primed cDNA was generated during the reverse transcription
      step in an assay employing unmodified primers and several reverse transcriptases.
      As a result, a qRT-PCR assay using the thermostable rTth in combination with
      tagged primers was developed, which greatly improved strand specificity by
      circumventing the events of self- and false-priming. The reliability of the assay
      was then addressed in vitro using BV-2 microglia cells as well as in C57/BL6
      mice. It was possible to follow the kinetics of positive and negative-strand RNA
      synthesis both in vitro and in vivo; however, the sensitivity of the assay will
      need to be optimized in order to detect and quantify negative-strand RNA
      synthesis in the very early stages of infection. Overall, the strand-specific qRT
      PCR assay developed in this study is an effective tool to quantify WNV RNA,
      reassess viral replication, and study tropism of WNV in the context of WNV
      pathogenesis. 

PMID- 23965253
TI  - Small molecule inhibitors of WNT/beta-catenin signaling block IL-1beta- and
      TNFalpha-induced cartilage degradation.
AB  - INTRODUCTION: In this study, we tested the ability of small molecule inhibitors
      of WNT/beta-catenin signaling to block interleukin 1beta (IL-1beta)- and tumor
      necrosis factor alpha (TNFalpha)-induced cartilage degradation. Proinflammatory
      cytokines such as IL-1beta and TNFalpha are potent inducers of cartilage
      degradation by upregulating matrix metalloproteinase (MMP) expression and
      activity. Because WNT/beta-catenin signaling was found to be involved in IL-1beta
      and TNFalpha-induced upregulation of MMP activity, we hypothesized that
      inhibition of WNT/beta-catenin signaling might block IL-1beta- and TNFalpha
      induced cartilage degradation. We tested the effect of small molecules that block
      the interaction between beta-catenin and TCF/Lef transcription factors on IL
      1beta- and TNFalpha-induced cartilage degradation in mouse fetal metatarsals.
      METHODS: We used mouse fetal metatarsals treated with IL-1beta and TNFalpha as an
      ex vivo model for cytokine-induced cartilage degradation. Metatarsals were
      treated with IL-1beta and TNFalpha in combination with the small molecules PKF115
      584, PKF118-310 and CGP049090 at different concentrations and then harvested them
      for histological and gene expression analysis. RESULTS: We found that IL-1beta-
      and TNFalpha-induced cartilage degradation in mouse fetal metatarsals was blocked
      by inhibiting WNT/beta-catenin signaling using small molecule PKF115-584 and
      partially using CGP049090 dose-dependently. In addition, we found that PKF115-584
      blocked IL-1beta- and TNFalpha-induced MMP mRNA expression, but did not reverse
      the inhibitory effect of IL-1beta on the expression of cartilage anabolic genes.
      CONCLUSION: In this study, we show that inhibition of WNT/beta-catenin signaling
      by small molecules can effectively prevent IL-1beta- and TNFalpha-induced
      cartilage degradation by blocking MMP expression and activity. Furthermore, we
      elucidate the involvement of WNT/beta-catenin signaling in IL-1beta- and TNFalpha
      induced cartilage degradation.

PMID- 23965254
TI  - Analysis of the security and privacy requirements of cloud-based electronic
      health records systems.
AB  - BACKGROUND: The Cloud Computing paradigm offers eHealth systems the opportunity
      to enhance the features and functionality that they offer. However, moving
      patients' medical information to the Cloud implies several risks in terms of the
      security and privacy of sensitive health records. In this paper, the risks of
      hosting Electronic Health Records (EHRs) on the servers of third-party Cloud
      service providers are reviewed. To protect the confidentiality of patient
      information and facilitate the process, some suggestions for health care
      providers are made. Moreover, security issues that Cloud service providers should
      address in their platforms are considered. OBJECTIVE: To show that, before moving
      patient health records to the Cloud, security and privacy concerns must be
      considered by both health care providers and Cloud service providers. Security
      requirements of a generic Cloud service provider are analyzed. METHODS: To study
      the latest in Cloud-based computing solutions, bibliographic material was
      obtained mainly from Medline sources. Furthermore, direct contact was made with
      several Cloud service providers. RESULTS: Some of the security issues that should
      be considered by both Cloud service providers and their health care customers are
      role-based access, network security mechanisms, data encryption, digital
      signatures, and access monitoring. Furthermore, to guarantee the safety of the
      information and comply with privacy policies, the Cloud service provider must be
      compliant with various certifications and third-party requirements, such as SAS70
      Type II, PCI DSS Level 1, ISO 27001, and the US Federal Information Security
      Management Act (FISMA). CONCLUSIONS: Storing sensitive information such as EHRs
      in the Cloud means that precautions must be taken to ensure the safety and
      confidentiality of the data. A relationship built on trust with the Cloud service
      provider is essential to ensure a transparent process. Cloud service providers
      must make certain that all security mechanisms are in place to avoid unauthorized
      access and data breaches. Patients must be kept informed about how their data are
      being managed.

PMID- 23965256
TI  - The BMA and its staff's private health cover.

PMID- 23965255
TI  - A randomized trial of practice facilitation to improve the delivery of chronic
      illness care in primary care: initial and sustained effects.
AB  - BACKGROUND: Practice facilitation (PF) is an implementation strategy now commonly
      used in primary care settings for improvement initiatives. PF occurs when a
      trained external facilitator engages and supports the practice in its change
      efforts. The purpose of this group-randomized trial is to assess PF as an
      intervention to improve the delivery of chronic illness care in primary care.
      METHODS: A randomized trial of 40 small primary care practices who were
      randomized to an initial or a delayed intervention (control) group. Trained
      practice facilitators worked with each practice for one year to implement
      tailored changes to improve delivery of diabetes care within the Chronic Care
      Model framework. The Assessment of Chronic Illness Care (ACIC) survey was
      administered at baseline and at one-year intervals to clinicians and staff in
      both groups of practices. Repeated-measures analyses of variance were used to
      assess the main effects (mean differences between groups) and the within-group
      change over time. RESULTS: There was significant improvement in ACIC scores (p <
      0.05) within initial intervention practices, from 5.58 (SD 1.89) to 6.33 (SD
      1.50), compared to the delayed intervention (control) practices where there was a
      small decline, from 5.56 (SD 1.54) to 5.27 (SD 1.62). The increase in ACIC scores
      was sustained one year after withdrawal of the PF intervention in the initial
      intervention group, from 6.33 (SD 1.50) to 6.60 (SD 1.94), and improved in the
      delayed intervention (control) practices during their one year of PF
      intervention, from 5.27 (SD 1.62) to 5.99 (SD 1.75). CONCLUSIONS: Practice
      facilitation resulted in a significant and sustained improvement in delivery of
      care consistent with the CCM as reported by those involved in direct patient care
      in small primary care practices. The impact of the observed change on clinical
      outcomes remains uncertain. TRIAL REGISTRATION: This protocol followed the
      CONSORT guidelines and is registered per ICMJE guidelines: CLINICAL TRIAL
      REGISTRATION NUMBER: NCT00482768.

PMID- 23965257
TI  - Condom use at sexual debut among Chinese youth.
AB  - Chinese youth represent a high-risk group for sexually transmitted infections and
      unintended pregnancies, but there is little understanding of their sexual
      behaviours. Using nationally representative data, this study examines the social
      and demographic correlates of condom use by Chinese youth at sexual debut. It
      also examines the relationship context of condom use at sexual debut. The results
      indicate that condom use at sexual debut is very low in China, confirming that
      youth are a high-risk group. The results demonstrate that age and educational
      attainment are the primary indicators of condom use. Early sexual debut
      associates with a greater risk of unsafe sex at sexual debut and higher
      educational attainment increases the likelihood of self-protecting behaviours.
      The likelihood of self-protection also increases when sexual partners plan their
      sexual debut or discuss contraception beforehand. The results suggest that
      interventions are needed to provide youth with better knowledge about self
      protection.

PMID- 23965259
TI  - Andrew Wyeth and N.C. Wyeth: a psychodynamic perspective on father and son.
AB  - This paper examines the relationship between two extraordinary artists, father
      and son--N.C. Wyeth (1882-1945) and Andrew Wyeth (1917-2009)--and their art. N.C.
      Wyeth, the father, the most famous illustrator of his day, painted scenes full of
      drama and action, often of men engaged in violent life and death struggles. N.C.
      was unable to separate from his powerful mother and yearned for his iconic
      father. He thought himself an artistic failure and dedicated himself to raising
      his children to be geniuses. The youngest son, Andrew Wyeth, who lived a "secret
      life," painted scenes often characterized by pathos: bleak and barren landscapes,
      leaden skies, tire tracks, gray framed houses, desiccated fields, and circling
      buzzards. In the father-son relationship, we often seen three themes perpetuated
      developmentally: (1) the son's identification with the innermost conflicts of his
      father; (2) the yearning for the iconic father of his youth; and (3) a
      continuation and disavowal of his father's life. These themes are played out in
      the relationship between Andrew Wyeth and his father.

PMID- 23965258
TI  - Dual effects of single-walled carbon nanotubes coupled with near-infrared
      radiation on Bacillus anthracis spores: inactivates spores and stimulates the
      germination of surviving spores.
AB  - BACKGROUND: Bacillus anthracis is a pathogen that causes life-threatening disease
      -anthrax. B. anthracis spores are highly resistant to extreme temperatures and
      harsh chemicals. Inactivation of B. anthracis spores is important to ensure the
      environmental safety and public health. The 2001 bioterrorism attack involving
      anthrax spores has brought acute public attention and triggered extensive
      research on inactivation of B. anthracis spores. Single-walled carbon nanotubes
      (SWCNTs) as a class of emerging nanomaterial have been reported as a strong
      antimicrobial agent. In addition, continuous near infrared (NIR) radiation on
      SWCNTs induces excessive local heating which can enhance SWCNTs' antimicrobial
      effect. In this study, we investigated the effects of SWCNTs coupled with NIR
      treatment on Bacillus anthracis spores. RESULTS AND DISCUSSION: The results
      showed that the treatment of 10 MUg/mL SWCNTs coupled with 20 min NIR
      significantly improved the antimicrobial effect by doubling the percentage of
      viable spore number reduction compared with SWCNTs alone treatment (88% vs. 42%).
      At the same time, SWCNTs-NIR treatment activated the germination of surviving
      spores and their dipicolinic acid (DPA) release during germination. The results
      suggested the dual effect of SWCNTs-NIR treatment on B. anthracis spores:
      enhanced the sporicidal effect and stimulated the germination of surviving
      spores. Molecular level examination showed that SWCNTs-NIR increased the
      expression levels (>2-fold) in 3 out of 6 germination related genes tested in
      this study, which was correlated to the activated germination and DPA release.
      SWCNTs-NIR treatment either induced or inhibited the expression of 3 regulatory
      genes detected in this study. When the NIR treatment time was 5 or 25 min, there
      were 3 out of 7 virulence related genes that showed significant decrease on
      expression levels (>2 fold decrease). CONCLUSIONS: The results of this study
      demonstrated the dual effect of SWCNTs-NIR treatment on B. anthracis spores,
      which enhanced the sporicidal effect and stimulated the germination of surviving
      spores. SWCNTs-NIR treatment also altered the expression of germination,
      regulatory, and virulence-related genes in B. anthracis.

PMID- 23965260
TI  - Motivational pharmacotherapy: combining motivational interviewing and
      antidepressant therapy to improve treatment adherence.
AB  - Treatment non-adherence in psycho-pharmacotherapy remains a significant challenge
      to the effective clinical management of psychiatric disorders, especially among
      underserved racial/ethnic groups. This article introduces motivational
      pharmacotherapy, an approach that integrates motivational interviewing into
      psycho-pharmacotherapy sessions in order to increase treatment adherence. We
      describe what aspects of motivational interviewing were incorporated into
      motivational pharmacotherapy and how we tailored the intervention to the clinical
      and cultural characteristics of monolingual Spanish-speaking immigrants with
      major depressive disorder. Transcriptions of the interactions between
      psychiatrists and patients help illustrate this approach. In our experience,
      motivational pharmacotherapy differs substantially from standard pharmacotherapy
      in how it recasts clinicians and patients as equal experts, prioritizes patients'
      motivation to engage in treatment rather than clinicians' multiple inquiries
      about symptoms, encourages patients' self-efficacy to overcome barriers, and
      attends to the momentum of patients' language about commitment to change. We also
      found that motivational pharmacotherapy can be feasibly incorporated into
      medication treatment, can be tailored to patients' culture and disorder, and may
      help increase adherence to psycho-pharmacotherapy. 

PMID- 23965263
TI  - The relationship of PTSD to negative cognitions: a 17-year longitudinal study.
AB  - With the growing interest in the role of cognitions in PTSD, this prospective
      study examined the course and bi-directional relationship between post-trauma
      cognitions and symptoms of PTSD. A sample of Israeli combat veterans, including
      former prisoners of war, was assessed in 1991, and later followed up in 2003 and
      2008. PTSD symptoms were measured at three time points. Cognitions concerning the
      self and the world were measured twice. Applying autoregressive cross-lagged
      (ARCL) modeling strategy, initial PTSD symptoms predicted subsequent negative
      cognitions but not vice versa. In addition, repeated measures design revealed
      that individuals with chronic PTSD symptoms had relatively negative cognitions
      that further amplified with time. More specifically, increasingly negative
      cognitions were documented among ex-prisoners of war. The main findings suggest
      that negative cognitions are fueled by PTSD and that in chronic PTSD there is an
      amplification of pathogenic outcomes over time. Discussion of the findings is in
      the context of current cognitive models of PTSD.

PMID- 23965262
TI  - A characterization of adult victims of sexual violence: results from the national
      epidemiological survey for alcohol and related conditions.
AB  - Sexual violence can cause acute and persistent negative psychological outcomes
      among children and adults in a community. Previous studies have frequently
      reported high prevalence of prior child and adolescent sexual abuse among adult
      victims of sexual violence. This raises uncertainty over the specific
      contribution of sexual victimization in adulthood to the adverse psychological
      outcomes. The present study draws on a large nationally representative sample of
      adults without history of childhood sexual abuse, and applies diagnostic criteria
      of DSM-IV, in order to investigate the risk factors and psychiatric comorbidities
      correlated with sexual victimization in adulthood. In a large representative
      sample of U.S. adults without history of childhood sexual abuse, 2.5% reported
      sexual victimization in adulthood. Female gender, living alone, economic
      disadvantage, and a history of childhood adversities and parental psychopathology
      were identified as risk factors. Adult sexual victimization increased the risk of
      developing a variety of psychiatric disorders, especially PTSD (HR = 3.43, 95% CI
      [2.67, 4.41]) and drug abuse (HR = 3.38, 95% CI [2.49, 4.58]). Conversely, pre
      existing psychiatric psychopathology, particularly PTSD (HR = 3.99, 95% CI [2.68,
      5.94]) and dysthymia (HR = 2.26, 95% CI [1.42, 3.59]), increased the likelihood
      of sexual victimization in adulthood. Childhood experience and adulthood
      sociodemographic characteristics are important in affecting the risk of being
      sexually victimized in adulthood. Psychiatric disorders can act as both risk
      factors and outcomes of adult sexual victimization. 

PMID- 23965261
TI  - Impact of motivational pharmacotherapy on treatment retention among depressed
      Latinos.
AB  - Compared to non-Latino Whites, U.S. racial/ethnic minority groups show higher non
      adherence with outpatient antidepressant therapy, including lower retention,
      despite adjusting for sociodemographic and insurance covariates. Culturally
      salient concerns about antidepressants leading to ambivalence about treatment
      engagement may contribute to this discrepancy. To improve treatment adherence
      among depressed Latinos, we developed motivational pharmacotherapy, a novel
      approach that combines motivational interviewing, standard pharmacotherapy, and
      attention to Latino cultural concerns about antidepressants. This 12-week, open
      trial, pre-post pilot study assessed the impact of motivational pharmacotherapy
      on antidepressant therapy retention, response (symptoms, functioning, and quality
      of life), and visit duration among n = 50 first-generation Latino outpatients
      with major depressive disorder. At study endpoint, 20% of patients discontinued
      treatment, with a mean therapy duration of 74.2 out of 84 days. Patients'
      symptoms, psychosocial functioning, and quality of life improved significantly.
      Mean visit length was 36.7 minutes for visit 1 and 24.3 minutes for subsequent
      visits, compatible with use in community clinics. Responder and remitter rates
      were 82% and 68%. Compared to published Latino proportions of non-retention (32
      53%) and previous studies at our clinic with similar samples and medications (36
      46%), Motivational pharmacotherapy appears to improve Latino retention in
      antidepressant therapy and should be investigated further in controlled designs. 

PMID- 23965264
TI  - Gender differences in the risk and protective factors associated with PTSD: a
      prospective study of National Guard troops deployed to Iraq.
AB  - This study examines gender differences in post-traumatic stress symptoms (PTSS)
      and PTSS risk/protective factors among soldiers deployed to Iraq. We pay special
      attention to two potentially modifiable military factors, military preparedness
      and unit cohesion, which may buffer the deleterious psychological effects of
      combat. Longitudinal data were collected on 922 New Jersey National Guard
      soldiers (91 women) deployed to Iraq in 2008. Anonymous surveys administered at
      pre- and post-deployment included the PTSD Checklist (PCL), the Unit Support
      Scale, and a preparedness scale adapted from the Iowa Gulf War Study. Bivariate
      analyses and hierarchical multiple regression were used to identify predictors of
      PTSS and their explanatory effects on the relationship between gender and PTSS.
      Women had a higher prevalence of probable post-deployment PTSD than men (18.7%
      vs. 8.7%; OR = 2.45; CI [1.37, 4.37]) and significantly higher post-deployment
      PTSS (33.73 vs. 27.37; p = .001). While there were no gender differences in
      combat exposure, women scored higher on pre-deployment PTSS (26.9 vs. 23.1; p <=
      .001) and lower on military preparedness (1.65 vs. 2.41; p <= .001) and unit
      cohesion (32.5 vs. 38.1; p <= .001). In a multivariate model, controlling for all
      PTSS risk/resilience factors reduced the gender difference as measured by the
      unstandardized Beta (B) by 45%, with 18% uniquely attributable to low cohesion
      and low preparedness. In the fully controlled model, gender remained a
      significant predictor of PTSS but the effect size was small (d = .26). Modifiable
      military institutional factors may account for much of the increased
      vulnerability of women soldiers to PTSD. 

PMID- 23965265
TI  - Synergistic effects of COMT and TPH2 on social cognition.
AB  - Whether genetic factors affect social cognition, particularly emotion management,
      requires elucidation. This study investigates whether social cognition varies
      with genetic variations of COMT and tryptophan hydroxylase-2 (TPH2), which
      modulate dopamine and serotonin neurotransmissions respectively, and thereby
      emotion regulation. NIMH-recommended "managing emotions branch and 2 subtasks" of
      MSCEIT and six neurocognition domains, and genotypes of COMT Val158Met and TPH2
      G703T were measured in 150 Han-Chinese healthy adults. Subjects carrying the M
      allele (M group) of COMT exceeded Val/Val homozygotes (V group) in managing
      emotions branch (p = 0.032) and emotional relation subtask (p = 0.037). TPH2 T/T
      homozygotes (T group) excelled those with the G allele (G group) in emotional
      management subtask (p = 0.025). Subjects with M+T variation surpassed the other 3
      groups (M+G, V+T and V+G) in managing emotion branch (p = 0.002), emotional
      relation subtask (p = 0.023), and emotional management subtask (p = 0.002). The
      findings remained after control for gender, age, education, and neurocognitive
      functions. Synergistically, the effect size of COMT-TPH2 combination surmounted
      the sum of separate effect sizes of COMT and TPH2. The findings suggest that
      genetic variations of COMT and TPH2 have synergistic effects on social cognition
      in the general population. 

PMID- 23965266
TI  - Epistasis and complex neuropsychiatric phenotypes.

PMID- 23965270
TI  - Complete genome sequence of Streptomyces fulvissimus.
AB  - The complete genome sequence of Streptomyces fulvissimus (DSM 40593), consisting
      of a linear chromosome with a size of 7.9Mbp, is reported. Preliminary data
      indicates that the chromosome of S. fulvissimus contains 32 putative gene
      clusters involved in the biosynthesis of secondary metabolites, two of them
      showing very high similarity to the valinomycin and nonactin biosynthetic
      clusters. The availability of genome sequence of S. fulvissimus will contribute
      to the evaluation of the full biosynthetical potential of streptomycetes. 

PMID- 23965271
TI  - The production of class III plant peroxidases in transgenic callus cultures
      transformed with the rolB gene of Agrobacterium rhizogenes.
AB  - The production of plant peroxidases by plant cell cultures is of great interest
      because of the potential for industrial applications. We used plant cell cultures
      overexpressing the rolB gene to produce increased amounts of plant class III
      peroxidases. The rolB gene ensured the stable and permanent activation of
      peroxidase activity in the transformed callus cultures of different plants. In
      particular, the total peroxidase activity in transformed Rubia cordifolia cells
      was increased 23-86-fold, and the abundance of the major peroxidase gene
      transcripts was increased 17-125-fold (depending on the level of rolB expression)
      compared with non-transformed control calli. The peroxidase-activating effect of
      rolB was greater than that of other peroxidase inducers, such as external
      stresses and methyl jasmonate. 

PMID- 23965272
TI  - Characterization of the glutamate-specific endopeptidase from Bacillus
      licheniformis expressed in Escherichia coli.
AB  - Glutamate-specific endopeptidase from Bacillus licheniformis (GSE-BL) is widely
      used in peptide recovery and synthesis because of its unique substrate
      specificity. However, the mechanism underlying its specificity is still not
      thoroughly understood. In this study, the roles of the prosegment and key amino
      acids involved in the proteolytic activity of GSE-BL were investigated. Loss of
      the GSE-BL prosegment severely restricted enzymatic activity toward Z-Phe-Leu-Glu
      pNA. A homologous model of GSE-BL revealed that it contains the catalytic triad
      "His47, Asp96 and Ser 167", which was further confirmed by site-directed
      mutagenesis. In vitro mutagenesis further indicated that Val2, Arg89 and His190
      are essential for enzymatic activity toward Z-Phe-Leu-Glu-pNA. Moreover, the
      catalytic efficiency of Phe57Ala GSE-BL toward Z-Phe-Leu-Glu-pNA was 50% higher
      than that of the native mature GSE-BL. This is the first study to fully elucidate
      the key amino acids for proteolytic activity of GSE-BL. Mature GSE-BL could be
      obtained through self-cleavage alone when Lys at -1 position was replaced by Glu,
      providing a new strategy for the preparation of mature GSE-BL. This study yielded
      some valuable insights into the substrate specificity of glutamate-specific
      endopeptidase, establishing a foundation for broadening the applications of GSE
      BL. 

PMID- 23965273
TI  - Kinetics of continuous cultivation of the oleaginous yeast Rhodosporidium
      toruloides.
AB  - Microbial lipids are potential alternative feedstock for biofuel and oleochemical
      industries. The oleaginous yeast Rhodosporidium toruloides AS 2.1389 is an
      excellent lipid producer. To attain parameters for the understanding of the lipid
      production process, we performed continuous cultivation experiments under either
      carbon or nitrogen limitation. The maintenance coefficient and maximum cell mass
      yield for this yeast were determined as 5.7 mg glucose/g cell/h and 0.42 g cell/g
      glucose, respectively, under carbon limitation. Under nitrogen limitation, the
      highest lipid yield of 0.19 g/g was observed at the dilution rate of 0.02 h(-1)
      while the highest specific lipid formation rate of 0.058 g/g cell/h at the
      dilution rate of 0.08 h(-1). A kinetic model of lipid formation under steady
      state conditions was developed, parameters estimated, and optimal continuous
      cultivation conditions forecasted. These data should be very helpful to develop
      and design more efficient bioprocesses for microbial lipid production.

PMID- 23965274
TI  - Who does what in prehospital critical care? An analysis of competencies of
      paramedics, critical care paramedics and prehospital physicians.
AB  - INTRODUCTION: Emergency medical services in the UK are facing the challenge of
      responding to an increasing number of calls, often for non-emergency care, while
      also providing critical care to the few severely ill or injured patients. In
      response, paramedic training in the UK has been extended and there are regional
      strategies to improve prehospital critical care (PHCC). We describe the clinical
      competencies of three groups of prehospital providers in the UK with the aim of
      informing future planning of the delivery of PHCC. METHODS: We used a data
      triangulation approach to obtain lists of competencies for paramedics, critical
      care paramedics (CCPs) and PHCC physicians of the Great Western Ambulance
      Service. Data sources were professional guidance documents, equipment available
      to the provider, log sheets of prehospital care episodes, direct observations and
      a survey of providers. RESULTS: We identified 389, 441 and 449 competencies for
      paramedics, CCPs and PHCC physicians, respectively. Competencies of CCPs and PHCC
      physicians which exceeded those of paramedics can be arranged in four distinct
      clusters: induction and maintenance of anaesthesia, procedural sedation, advanced
      cardiovascular management and complex invasive interventions. DISCUSSION:
      Paramedics possess a considerable number of competencies which allow them to
      diagnose and treat a variety of conditions. CCPs and PHCC physicians possess a
      few additional critical care competencies which are potentially life-saving but
      are required infrequently and can carry significant risks. Concentration of
      training and clinical exposure for a small group of providers in critical care
      teams can help optimising benefits and reducing risks of PHCC.

PMID- 23965275
TI  - Deep vein thrombosis: remember the mechanical causes.

PMID- 23965276
TI  - High-sensitivity cardiac troponin T is an independent predictor of inhospital
      mortality in emergency department patients with suspected infection: a
      prospective observational derivation study.
AB  - INTRODUCION: To assess the prognostic and discriminative accuracy of high
      sensitivity cardiac troponin T (hs-cTnT) for prediction of inhospital mortality
      in emergency department (ED) patients with suspected infection. METHODS:
      Prospective observational derivation study in ED patients with suspected
      infection. Prognostic performance of hs-cTnT (divided in four quartiles because
      of non-linearity) for prediction of inhospital mortality was assessed using
      multivariable logistic regression, correcting for predisposition, infection,
      response and organ failure (PIRO) score as a measure of illness severity and
      quality of ED treatment as quantified by the number of 'Surviving Sepsis
      Campaign' goals achieved. Discriminative power of hs-cTnT was assessed by
      receiver operator characteristics with area under the curve (AUC) analysis.
      RESULTS: Hs-cTnT (median (IQR) was 57 (25-90) ng/L (n=23) in non-survivors,
      significantly higher than the 15 (7-28) ng/L in survivors (n=269, p<0.001).
      Additionally, the lowest quartile of hs-cTnT was a perfect predictor of survival
      because zero death occurred. Therefore, the second quartile was used as a
      reference category in the multivariable logistic regression analysis showing that
      hs-cTnT was an independent predictor of inhospital mortality: Corrected ORs were
      2.2 (95% CI 0.4 to 12.1) and 5.8 (1.2 to 27.3) for the 3rd and 4th quartile
      compared with the 2nd hs-cTnT quartile. The AUCs of hs-TnT was 0.81 (0.74 to
      0.88), similar to the AUC of 0.78 (0.68 to 0.87) of the PIRO score (p>0.05).
      Overall negative predictive value of hs-cTnT was 99%. CONCLUSIONS: In ED patients
      with suspected infection, the routinely used biomarker hs-cTnT is an independent
      predictor of inhospital mortality with excellent discriminative performance.
      Future studies should focus on the additional value of hs-cTnT to existing risk
      stratification tools.

PMID- 23965277
TI  - Vegetarians are not less colonized with extended-spectrum-beta-lactamase
      producing bacteria than meat eaters.

PMID- 23965278
TI  - Pulmonary function after less invasive anterior instrumentation and fusion for
      idiopathic thoracic scoliosis.
AB  - PURPOSE: Standard thoracotomy for anterior instrumentation and fusion of the
      thoracic spine in idiopathic scoliosis may have detrimental effects on pulmonary
      function. In this study we describe a less invasive anterior surgical technique
      and show the pre- and postoperative pulmonary function with a minimum follow-up
      of 2 years. METHODS: Twenty patients with Lenke type 1 adolescent thoracic
      idiopathic scoliosis were treated with anterior spinal fusion and
      instrumentation. The mean preoperative Cobb angle of the thoracic curve was 53
      degrees  +/- 5.8. Pulmonary function tests (PFT) and radiographic evaluation was
      performed. RESULTS: The mean postoperative correction in Cobb angle of the
      thoracic curve was 27 degrees  +/- 8.2 (49%).The mean preoperative FEV1 was 2.81
      +/- 0.43 L, which increased to 3.14 +/- 0.50 L at 2 years postoperatively (P =
      0.000). The mean FEV1% did not change (89.60 +/- 7.49% preoperatively, versus
      90.53 +/- 5.95% at 2 years follow-up, P = 0.467). The TLC increased from 4.62 +/-
      0.62 L preoperatively to 5.17 +/- 0.63 L at 2 years follow-up (P = 0.000). The
      FEV1% at two years of follow-up improved to 104% of the FEV1% predicted value.
      The FEV1 improved to 97% of the FEV1 predicted value. CONCLUSION: Anterior spinal
      fusion for idiopathic scoliosis by means of a minimal open thoracotomy proved to
      be a safe surgical technique that resulted in an improvement of pulmonary
      function. Our results are similar to those of thoracoscopic procedures reported
      in literature.

PMID- 23965280
TI  - Social support during delivery in rural central Ghana: a mixed methods study of
      women's preferences for and against inclusion of a lay companion in the delivery
      room.
AB  - This study aimed to explore pregnant women's attitudes towards the inclusion of a
      lay companion as a source of social support during labour and delivery in rural
      central Ghana. Quantitative demographic and pregnancy-related data were collected
      from 50 pregnant women presenting for antenatal care at a rural district hospital
      and analysed using STATA/IC 11.1. Qualitative attitudinal questions were
      collected from the same women through semi-structured interviews; data were
      analysed using NVivo 9.0. Twenty-nine out of 50 women (58%) preferred to have a
      lay companion during facility-based labour and delivery, whereas 21 (42%)
      preferred to deliver alone with the nurses in a facility. Women desiring a
      companion were younger, had more antenatal care visits, had greater educational
      attainment and were likely to be experiencing their first delivery. Women varied
      in the type of companion they prefer (male partner vs female relative). What was
      expected in terms of social support differed based upon the type of companion.
      Male companions were expected to provide emotional support and to 'witness her
      pain'. Female companions were expected to provide emotional support as well as
      instrumental, informational and appraisal support. Three qualitative themes were
      identified that run counter to the inclusion of a lay helper: fear of an evil
      spirited companion, a companion not being necessary or helpful, and being 'too
      shy' of a companion. This research challenges the assumption of a unilateral
      desire for social support during labour and delivery, and suggests that women
      differ in the type of companion and type of support they prefer during facility
      deliveries. Future research is needed to determine the direction of the
      relationship--whether women desire certain types of support and thus choose
      companions they believe can meet those needs, or whether women desire a certain
      companion and adjust their expectations accordingly.

PMID- 23965279
TI  - South Asian Heart Risk Assessment (SAHARA): Randomized Controlled Trial Design
      and Pilot Study.
AB  - BACKGROUND: People of South Asian origin suffer a high burden of premature
      myocardial infarction (MI). South Asians form a growing proportion of the
      Canadian population and preventive strategies to mitigate the risk of MI in this
      group are needed. Prior studies have shown that multimedia interventions are
      effective and feasible in inducing health behavior changes among the obese,
      smokers, and among those who are sedentary. OBJECTIVE: Among at-risk South Asians
      living in Canada, our objectives are to determine: (1) the feasibility of a
      culturally tailored multimedia intervention to induce positive behavioral changes
      associated with reduced MI risk factors, and (2) the effectiveness and
      acceptability of information communicated by individualized MI and genetic risk
      score (GRS) reports. METHODS: The South Asian HeArt Risk Assessment (SAHARA)
      pilot study enrolled 367 individuals of South Asian origin recruited from places
      of worship and community centers in Ontario, Canada. MI risk factors including
      the 9p21 genetic variant status were provided to all participants after the
      baseline visit. Participants were randomly allocated to receive a multimedia
      intervention or control. The intervention group selected health goals and
      received personalized health messages to promote adherence to their selected
      goals. After 6 months, all participants had their MI risk factors repeated. The
      methods and results of this study are reported based on the CONSORT-EHEALTH
      guidelines. RESULTS: The mean age of participants was 53.8 years (SD 11.4), 52.0%
      (191/367) were women, and 97.5% (358/367) were immigrants to Canada. The mean
      INTERHEART risk score was 13.0 (SD 5.8) and 73.3% (269/367) had one or two copies
      of the risk allele for the 9p21 genetic variant. Both the intervention and
      control groups made some progress in health behavior changes related to diet and
      physical activity over 6 months. Participants reported that their risk score
      reports motivated behavioral changes, although half of the participants could not
      recall their risk scores at the end of study evaluation. Some components of the
      multimedia intervention were not widely used such as logging onto the website to
      set new health goals, and participants requested having more personal
      interactions with the study team. CONCLUSIONS: Some, but not all, components of
      the multimedia intervention are feasible and have the potential to induce
      positive health behavior changes. MI and GRS reports are desired by participants
      although their impact on inducing sustained health behavior change requires
      further evaluation. Information generated from this pilot study has directly
      informed the design of another randomized trial designed to reduce MI risk among
      South Asians. TRIAL REGISTRATION: ClinicalTrials.gov NCT01577719;
      http://clinicaltrials.gov/ct2/show/NCT01577719 (Archived by WebCite at
      http://www.webcitation.org/6J11uYXgJ).

PMID- 23965281
TI  - Chitosan-based siRNA delivery systems.
AB  - Recently, chitosan has attracted significant attention in the formulation of
      small interfering RNA (siRNA). Because of its cationic nature, chitosan can
      easily complex siRNA, thus readily forming nanoparticles. Moreover, chitosan is
      biocompatible and biodegradable, which make it a good candidate for siRNA
      delivery in vivo. However, chitosan requires further development to achieve high
      efficiency. This review will describe the major barriers that impair the
      efficiency of the chitosan-based siRNA delivery systems, including the stability
      of the delivery system in biological fluids and endosomal escape. Several
      solutions to counteract these barriers have been developed and will be discussed.
      The parameters to consider for designing powerful delivery systems will be
      described, particularly the possibilities for grafting targeting ligands.
      Finally, optimized systems that allow in vivo therapeutic applications for both
      local and systemic delivery will be reviewed. This review will present recent
      improvements in chitosan-based siRNA delivery systems that overcome many of these
      system's previous pitfalls and pave the way to a new generation of siRNA delivery
      systems. 

PMID- 23965282
TI  - Anisakiasis mistaken for dientamoebiasis?

PMID- 23965283
TI  - Reply to Roser and Stensvold.

PMID- 23965284
TI  - Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized
      patients in china who had severe fever with thrombocytopenia syndrome.
AB  - BACKGROUND: The wide distribution and high case-fatality ratio of severe fever
      with thrombocytopenia syndrome (SFTS) have made it a significant public health
      problem. This study was designed to identify the predictors of fatal outcomes and
      to evaluate the effectiveness of antiviral therapy in treating SFTS virus (SFTSV)
      infected patients. METHODS: A cross-sectional study was performed in a general
      hospital located in Xinyang city, whereas the largest number of patients with
      SFTS in China were treated during 2011-2012. The primary outcome for the
      treatment effect analysis was death. Other outcomes included sequential platelet
      levels and viral loads observed throughout the hospitalization and the interval
      between the initiation of ribavirin therapy and the return of the platelet count
      to a normal level. RESULTS: A total of 311 SFTSV-infected patients were included
      in the study. The most frequent clinical presentations were fever, weakness,
      myalgia, and gastrointestinal symptoms. Each patient had thrombocytopenia,
      leukopenia, or both. The case-fatality ratio (CFR) was 17.4% (95% confidence
      interval [CI], 13.1%-21.6%). Older age (odds ratio [OR], 1.061; 95% CI, 1.023
      1.099; P = .001), decreased level of consciousness (OR, 5.397; 95% CI, 2.660
      10.948; P < .001), and elevated levels of lactate dehydrogenase (>1200 U/L; OR,
      2.620; 95% CI, 1.073-6.399; P = .035) and creatine kinase (>800 U/L; OR, 2.328;
      95% CI, 1.129-4.800; P = .022) were significantly associated with fatal outcome.
      The CFRs were similar between patients who received ribavirin and those who did
      not. Ribavirin treatment showed no significant effect on either platelet counts
      or viral loads during hospitalization of patients with fatal or nonfatal cases.
      CONCLUSIONS: These findings can improve knowledge about the characteristics of
      patients with fatal outcomes and the use of antiviral drug for SFTS.

PMID- 23965286
TI  - Assessment of natural radioactivity levels in rocks and their relationships with
      the geological structure of Johor state, Malaysia.
AB  - The distribution of natural radionuclides ((238)U, (232)Th and (40)K) and their
      radiological hazard effect in rocks collected from the state of Johor, Malaysia
      were determined by gamma spectroscopy using a high-purity germanium detector. The
      highest values of (238)U, (232)Th and (40)K activity concentrations (67+/-6, 85+/
      7 and 722+/-18 Bg kg(-1), respectively) were observed in the granite rock. The
      lowest concentrations of (238)U and (232)Th (2+/-0.1 Bq kg(-1) for (238)U and 2+/
      0.1 Bq kg(-1) for (232)Th) were observed in gabbro rock. The lowest concentration
      of (40)K (45+/-2 Bq kg(-1)) was detected in sandstone. The radium equivalent
      activity concentrations for all rock samples investigated were lower than the
      internationally accepted value of 370 Bq kg(-1). The highest value of radium
      equivalent in the present study (239+/-17 Bq kg(-1)) was recorded in the area of
      granite belonging to an acid intrusive rock geological structure. The absorbed
      dose rate was found to range from 4 to 112 nGy h(-1). The effective dose ranged
      from 5 to 138 MUSv h(-1). The internal and external hazard index values were
      given in results lower than unity. The purpose of this study is to provide
      information related to radioactivity background levels and the effects of
      radiation on residents in the study area under investigation. Moreover, the
      relationships between the radioactivity levels in the rocks within the geological
      structure of the studied area are discussed. 

PMID- 23965285
TI  - Cloning and biochemical characterization of an endo-1,4-beta-mannanase from the
      coffee berry borer Hypothenemus hampei.
AB  - BACKGROUND: The study of coffee polysaccharides-degrading enzymes from the coffee
      berry borer Hypothenemus hampei, has become an important alternative in the
      identification for enzymatic inhibitors that can be used as an alternative
      control of this dangerous insect. We report the cloning, expression and
      biochemical characterization of a mannanase gene that was identified in the
      midgut of the coffee berry borer and is responsible for the degradation of the
      most abundant polysaccharide in the coffee bean. METHODS: The amino acid sequence
      of HhMan was analyzed by multiple sequence alignment comparisons with BLAST
      (Basic Local Alignment Search Tool) and CLUSTALW. A Pichia pastoris expression
      system was used to express the recombinant form of the enzyme. The mannanase
      activity was quantified by the 3,5-dinitrosalicylic (DNS) and the hydrolitic
      properties were detected by TLC. RESULTS: An endo-1,4-beta-mannanase from the
      digestive tract of the insect Hypothenemus hampei was cloned and expressed as a
      recombinant protein in the Pichia pastoris system. This enzyme is 56% identical
      to the sequence of an endo-beta-mannanase from Bacillus circulans that belongs to
      the glycosyl hydrolase 5 (GH5) family. The purified recombinant protein (rHhMan)
      exhibited a single band (35.5 kDa) by SDS-PAGE, and its activity was confirmed by
      zymography. rHhMan displays optimal activity levels at pH 5.5 and 30 degrees C
      and can hydrolyze galactomannans of varying mannose:galactose ratios, suggesting
      that the enzymatic activity is independent of the presence of side chains such as
      galactose residues. The enzyme cannot hydrolyze manno-oligosaccharides such as
      mannobiose and mannotriose; however, it can degrade mannotetraose, likely through
      a transglycosylation reaction. The K(m) and k(cat) values of this enzyme on guar
      gum were 2.074 mg ml(-1) and 50.87 s(-1), respectively, which is similar to other
      mannanases. CONCLUSION: This work is the first study of an endo-1,4-beta
      mannanase from an insect using this expression system. Due to this enzyme's
      importance in the digestive processes of the coffee berry borer, this study may
      enable the design of inhibitors against endo-1,4-beta-mannanase to decrease the
      economic losses stemming from this insect.

PMID- 23965287
TI  - Concurrent whole brain radiotherapy and bortezomib for brain metastasis.
AB  - BACKGROUND: Survival of patients with brain metastasis particularly from
      historically more radio-resistant malignancies remains dismal. A phase I study of
      concurrent bortezomib and whole brain radiotherapy was conducted to determine the
      tolerance and safety of this approach in patients with previously untreated brain
      metastasis. METHODS: A phase I dose escalation study evaluated the safety of
      bortezomib (0.9, 1.1, 1.3, 1.5, and 1.7 mg/m2) given on days 1, 4, 8 and 11 of
      whole brain radiotherapy. Patients with confirmed brain metastasis were recruited
      for participation. The primary endpoint was the dose-limiting toxicity, defined
      as any >= grade 3 non-hematologic toxicity or grade >= 4 hematologic toxicity
      from the start of treatment to one month post irradiation. Time-to-Event
      Continual Reassessment Method (TITE-CRM) was used to determine dose escalation. A
      companion study of brain diffusion tensor imaging MRI was conducted on a subset
      of patients to assess changes in the brain that might predict delayed cognitive
      effects. RESULTS: Twenty-four patients were recruited and completed the planned
      therapy. Patients with melanoma accounted for 83% of all participants. The
      bortezomib dose was escalated as planned to the highest dose of 1.7 mg/m2/dose.
      No grade 4/5 toxicities related to treatment were observed. Two patients had
      grade 3 dose-limiting toxicities (hyponatremia and encephalopathy). A partial or
      minor response was observed in 38% of patients. Bortezomib showed greater
      demyelination in hippocampus-associated white matter structures on MRI one month
      after radiotherapy compared to patients not treated with bortezomib (increase in
      radial diffusivity +16.8% versus 4.8%; p = 0.0023). CONCLUSIONS: Concurrent
      bortezomib and whole brain irradiation for brain metastasis is well tolerated at
      one month follow-up, but MRI changes that have been shown to predict delayed
      cognitive function can be detected within one month of treatment.

PMID- 23965288
TI  - Assessment of global functioning in adolescents with autism spectrum disorders:
      utility of the Developmental Disability-Child Global Assessment Scale.
AB  - Assessment of global functioning is an important consideration in treatment
      outcome research; yet, there is little guidance on its evidence-based assessment
      for children with autism spectrum disorders. This study investigated the utility
      and validity of clinician-rated global functioning using the Developmental
      Disability-Child Global Assessment Scale in a sample of higher functioning
      adolescents with autism spectrum disorders and comorbid anxiety disorders
      enrolled in a randomized controlled trial (n = 30). Pretreatment Developmental
      Disability-Child Global Assessment Scale scores correlated with severity of
      autism spectrum disorders core symptoms (r = -.388, p = .034), pragmatic
      communication (r = .407, p = .032), and verbal ability (r = .449, p = .013) and
      did not correlate with severity of anxiety symptoms or with parent-reported
      adaptive behavior. Change in Developmental Disability-Child Global Assessment
      Scale scores during treatment was associated with autism spectrum disorders
      symptomatic improvement (r = .414, p = .040) and with improved general
      communication (r = .499, p = .013). Results support the importance of assessing
      global functioning in addition to symptom change and treatment response in
      clinical trials. 

PMID- 23965290
TI  - Intensity of human prion disease surveillance predicts observed disease
      incidence.
AB  - BACKGROUND: Prospective national screening and surveillance programmes serve a
      range of public health functions. Objectively determining their adequacy and
      impact on disease may be problematic for rare disorders. We undertook to assess
      whether objective measures of disease surveillance intensity could be developed
      for the rare disorder sporadic Creutzfeldt-Jakob disease (CJD) and whether such
      measures correlate with disease incidence. METHOD: From 10 countries with
      national human prion disease surveillance centres, the annual number of suspected
      prion disease cases notified to each national unit (n=17,610), referrals for
      cerebrospinal fluid (CSF) 14-3-3 protein diagnostic testing (n=28,780) and the
      number of suspect cases undergoing diagnostic neuropathological examination
      (n=4885) from 1993 to 2006 were collected. Age and survey year adjusted incidence
      rate ratios with 95% CIs were estimated using Poisson regression models to assess
      risk factors for sporadic, non-sporadic and all prion disease cases. RESULTS: Age
      and survey year adjusted analysis showed all three surveillance intensity
      measures (suspected human prion disease notifications, 14-3-3 protein diagnostic
      test referrals and neuropathological examinations of suspect cases) significantly
      predicted the incidence of sporadic CJD, non-sporadic CJD and all prion disease.
      CONCLUSIONS: Routine national surveillance methods adjusted as population rates
      allow objective determination of surveillance intensity, which correlates
      positively with reported incidence for human prion disease, especially sporadic
      CJD, largely independent of national context. The predictive relationship between
      surveillance intensity and disease incidence should facilitate more rapid
      delineation of aberrations in disease occurrence and assessment of the adequacy
      of disease monitoring by national registries.

PMID- 23965289
TI  - Greater medial temporal hypometabolism and lower cortical amyloid burden in ApoE4
      positive AD patients.
AB  - BACKGROUND: Apolipoprotein E epsilon4 (ApoE4) has been associated with an
      increased risk of Alzheimer's disease (AD), amyloid deposition and
      hypometabolism. ApoE4 is less prevalent in non-amnestic AD variants suggesting a
      direct effect on the clinical phenotype. However, the impact of ApoE4 on amyloid
      burden and glucose metabolism across different clinical AD syndromes is not well
      understood. We aimed to assess the relationship between amyloid deposition,
      glucose metabolism and ApoE4 genotype in a clinically heterogeneous population of
      AD patients. METHODS: 52 patients with probable AD (National Institute on Aging
      Alzheimer's Association) underwent [(11)C]Pittsburgh compound B (PIB) and
      [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. All
      patients had positive PIB-PET scans. 23 were ApoE4 positive (ApoE4+) (14
      heterozygous and 9 homozygous) and 29 were ApoE4 negative (ApoE4-). Groups
      consisted of language-variant AD, visual-variant AD and AD patients with amnestic
      and dysexecutive deficits. 52 healthy controls were included for comparison. FDG
      and PIB uptake was compared between groups on a voxel-wise basis and in regions
      of interest. RESULTS: While PIB patterns were diffuse in both patient groups,
      ApoE4- patients showed higher PIB uptake than ApoE4+ patients across the cortex.
      Higher PIB uptake in ApoE4- patients was particularly significant in right
      lateral frontotemporal regions. In contrast, similar patterns of hypometabolism
      relative to controls were found in both patient groups, mainly involving lateral
      temporoparietal cortex, precuneus, posterior cingulate cortex and middle frontal
      gyrus. Comparing patient groups, ApoE4+ subjects showed greater hypometabolism in
      bilateral medial temporal and right lateral temporal regions, and ApoE4- patients
      showed greater hypometabolism in cortical areas, including supplementary motor
      cortex and superior frontal gyrus. CONCLUSIONS: ApoE4+ AD patients showed lower
      global amyloid burden and greater medial temporal hypometabolism compared with
      matched ApoE4- patients. These findings suggest that ApoE4 may increase
      susceptibility to molecular pathology and modulate the anatomic pattern of
      neurodegeneration in AD.

PMID- 23965291
TI  - Bone response to buccal tooth movements-with and without flapless alveolar
      decortication.
AB  - SUMMARY OBJECTIVE: To evaluate the biological response of alveolar bone
      surrounding maxillary second premolars to flapless alveolar decortication and
      moderate, continuous forces in a buccal direction. MATERIALS AND METHODS: Using a
      randomized split-mouth experimental design, unilateral alveolar decortication was
      performed with a piezosurgery unit around the maxillary second premolars of six
      female dogs. The contralateral side received a sham surgery. The maxillary second
      premolars were moved buccally with archwires (initial 163.9 cN expansive force)
      for 9 weeks, followed by 2 weeks of consolidation. Intraoral, radiographic, and
      model measurements were performed to evaluate tooth movements; the amount and
      quality of surrounding bone were quantified using micro-CT; bone formation was
      evaluated histologically. RESULTS: The experimental premolars were expanded and
      tipped significantly (P < 0.05) more than the control premolars (1.35 times and
      2.05 times as much, respectively). Peak rates of tooth movement occurred around 5
      weeks. Dehiscenses were observed on both the experimental and control sides, with
      no statistically significant side differences in buccal bone height (BBH). Micro
      CT analyses showed less mature bone in the apico-buccal and cervico-lingual
      regions around the experimental teeth. Hematoxylin and eosin sections
      demonstrated fenestrations on the cervico-buccal bone on both sides. The
      experimental side showed substantially more new bone formation and modeling of
      apico-buccal, cervico-lingual, and buccal bone than the control side.
      CONCLUSIONS: Archwire expansion resulted in reductions in BBH. Piezosurgical
      flapless alveolar decortication, in combination with archwire expansion,
      increased tooth movements and tipping and produced less bone, less dense bone,
      and less mature bone.

PMID- 23965292
TI  - Blood synthetic cannabinoid concentrations in cases of suspected impaired
      driving.
AB  - Twelve cases of suspected impaired driving are discussed in which the drivers who
      subsequently tested positive for synthetic cannabinoid drugs underwent a
      psychophysical assessment. The attitude of the drivers was described as
      cooperative and relaxed, speech was slow and slurred and coordination was poor.
      Pulse and blood pressure were generally elevated. Horizontal gaze nystagmus was
      assessed in nine of the subjects, but was present in only two. The most
      consistent indicator was a marked lack of convergence. In all cases where a Drug
      Recognition Expert (DRE) officer evaluated and documented impairment (10 cases),
      it was attributed to the DRE cannabis category. Performance in field sobriety
      tests was variable, ranging from poor to minimal observable effect. Synthetic
      cannabinoid testing was performed by LC-MS-MS. Positive results included: JWH-018
      (n = 4), 0.1-1.1 ng/mL; JWH-081 (n = 2) qualitative only; JWH-122 (n = 3), 2.5
      ng/mL; JWH-210 (n = 4), 0.1 ng/mL; JWH-250 (n = 1), 0.38 ng/mL and AM-2201 (n =
      6), 0.43-4.0 ng/mL. While there is good evidence of psychophysical impairment in
      these subjects, further structured data collection is needed to fully assess the
      relationship between synthetic cannabinoid use and psychomotor and cognitive
      impairment. 

PMID- 23965293
TI  - Taeniases and cysticercosis in Indonesia: past and present situations.
AB  - The main aim of this study is to overview the past and present situations of
      human taeniases and cysticercosis in Indonesia and including future perspectives.
      Through joint projects from 1996, we have confirmed the occurrence of Taenia
      saginata (beef tapeworm) in Bali, of Taenia solium (pork tapeworm) mainly in
      Papua and sporadically in Bali, and of Taenia asiatica in North Sumatra. These
      taeniases were caused through eating uncooked pork and pig viscera for T. solium
      and T. asiatica, respectively, and beef for T. saginata. The distribution of
      these tapeworms in Indonesia is basically highly restricted by the traditional
      cultural and religious backgrounds in each island. T. saginata is relatively
      common in Bali although people consume pork 'lawar' more than beef 'lawar'.
      Taeniases due to T. saginata or T. asiatica and T. solium and cysticercosis due
      to T. solium have also been sporadically reported in some other islands. Among
      these species, T. solium is exceptional since humans can be infected not only by
      larval stages (cysticerci) in pork but also by eggs released from human tapeworm
      carriers. Cysticercosis has been confirmed in Indonesia in humans, pigs and even
      dogs.

PMID- 23965295
TI  - Involvement of delta and mu opioid receptors in the acute and sensitized
      locomotor action of cocaine in mice.
AB  - Analogs of deltorphins, such as cyclo(Ndelta, Ndelta-carbonyl-d-Orn2,
      Orn4)deltorphin (DEL-6) and deltorphin II N-(ureidoethyl)amide (DK-4) are
      functional agonists predominantly for the delta opioid receptors (DOR) in the
      guinea-pig ileum and mouse vas deferens bioassays. The purpose of this study was
      to examine an influence of these peptides (5, 10 or 20 nmol, i.c.v.) on the acute
      cocaine-induced (10mg/kg, i.p.) locomotor activity and the expression of
      sensitization to cocaine locomotor effect. Sensitization to locomotor effect of
      cocaine was developed by five injections of cocaine at the dose of 10mg/kg, i.p.
      every 3 days. Our results indicated that DK-4 and DEL-6 differently affected the
      acute and sensitized cocaine locomotion. Co-administration of DEL-6 with cocaine
      enhanced acute cocaine locomotion only at the dose of 10 nmol, with minimal
      effects at the doses 5 and 20 nmol, whereas co-administration of DK-4 with
      cocaine enhanced acute cocaine-induced locomotion in a dose-dependent manner.
      Similarly to the acute effects, DEL-6 only at the dose of 10 nmol but DK-4 dose
      dependently enhanced the expression of cocaine sensitization. Pre-treatment with
      DOR antagonist - naltrindole (5 nmol, i.c.v.) and mu opioid receptor (MOR)
      antagonist, beta-funaltrexamine abolished the ability of both peptides to
      potentiate the effects of cocaine. Our study suggests that MOR and DOR are
      involved in the interactions between cocaine and both deltorphins analogs. A
      distinct dose-response effects of these peptides on cocaine locomotion probably
      arise from differential functional activation (targeting) of the DOR and MOR by
      both deltorphins analogs.

PMID- 23965294
TI  - De novo likelihood-based measures for comparing genome assemblies.
AB  - BACKGROUND: The current revolution in genomics has been made possible by software
      tools called genome assemblers, which stitch together DNA fragments "read" by
      sequencing machines into complete or nearly complete genome sequences. Despite
      decades of research in this field and the development of dozens of genome
      assemblers, assessing and comparing the quality of assembled genome sequences
      still relies on the availability of independently determined standards, such as
      manually curated genome sequences, or independently produced mapping data. These
      "gold standards" can be expensive to produce and may only cover a small fraction
      of the genome, which limits their applicability to newly generated genome
      sequences. Here we introduce a de novo  probabilistic measure of assembly quality
      which allows for an objective comparison of multiple assemblies generated from
      the same set of reads. We define the quality of a sequence produced by an
      assembler as the conditional probability of observing the sequenced reads from
      the assembled sequence. A key property of our metric is that the true genome
      sequence maximizes the score, unlike other commonly used metrics. RESULTS: We
      demonstrate that our de novo  score can be computed quickly and accurately in a
      practical setting even for large datasets, by estimating the score from a
      relatively small sample of the reads. To demonstrate the benefits of our score,
      we measure the quality of the assemblies generated in the GAGE and Assemblathon 1
      assembly "bake-offs" with our metric. Even without knowledge of the true
      reference sequence, our de novo  metric closely matches the reference-based
      evaluation metrics used in the studies and outperforms other de novo  metrics
      traditionally used to measure assembly quality (such as N50). Finally, we
      highlight the application of our score to optimize assembly parameters used in
      genome assemblers, which enables better assemblies to be produced, even without
      prior knowledge of the genome being assembled. CONCLUSION: Likelihood-based
      measures, such as ours proposed here, will become the new standard for de novo 
      assembly evaluation.

PMID- 23965296
TI  - Effects of ghrelin on gastric distention sensitive neurons in the arcuate nucleus
      of hypothalamus and gastric motility in diabetic rats.
AB  - This study was performed to observe the effects of ghrelin on the activity of
      gastric distention (GD) sensitive neurons in the arcuate nucleus of hypothalamus
      (Arc) and on gastric motility in vivo in streptozocin (STZ) induced diabetes
      mellitus (DM) rats. Electrophysiological results showed that ghrelin could excite
      GD-excitatory (GD-E) neurons and inhibit GD-inhibitory (GD-I) neurons in the Arc.
      However, fewer GD-E neurons were excited by ghrelin and the excitatory effect of
      ghrelin on GD-E neurons was much weaker in DM rats. Gastric motility research in
      vivo showed that microinjection of ghrelin into the Arc could significantly
      promote gastric motility and it showed a dose-dependent manner. The effect of
      ghrelin promoting gastric motility in DM rats was weaker than that in normal
      rats. The effects induced by ghrelin could be blocked by growth hormone
      secretagogue receptor (GHSR) antagonist [d-Lys-3]-GHRP-6 or BIM28163. RIA and
      real-time PCR data showed that the levels of ghrelin in the plasma, stomach and
      ghrelin mRNA in the Arc increased at first but decreased later and the expression
      of GHSR-1a mRNA in the Arc maintained a low level in DM rats. The present
      findings indicate that ghrelin could regulate the activity of GD sensitive
      neurons and gastric motility via ghrelin receptors in the Arc. The reduced
      effects of promoting gastric motility induced by ghrelin could be connected with
      the decreased expression of ghrelin receptors in the Arc in diabetes. Our data
      provide new experimental evidence for the role of ghrelin in gastric motility
      disorder in diabetes. 

PMID- 23965297
TI  - Relationship between seizure episode and sudden cardiac arrest in patients with
      epilepsy: a community-based study.
AB  - BACKGROUND: Among patients with epilepsy, sudden cardiac arrest (SCA) is a major
      cause of death. It is commonly thought that SCA in epilepsy occurs after a
      seizure, though the strength of evidence supporting this is limited. We sought to
      evaluate the relationship between seizures and SCA in patients with epilepsy.
      METHODS AND RESULTS: From the ongoing Oregon Sudden Unexpected Death Study, cases
      of SCA identified using prospective, multisource ascertainment (Portland
      metropolitan area, Oregon; population~1 million; February 1, 2002, to March 1,
      2012) were evaluated for history of epilepsy. In the subset with witnessed SCA,
      clinical presentations were analyzed for evidence of seizure activity immediately
      before the event as well as lifetime clinical history, including nature of
      seizures before SCA. Only 34% of patients with history of epilepsy and a
      witnessed arrest had evidence of seizure activity before the arrest. Rates of
      survival to hospital discharge after attempted resuscitation were 2.7% in
      patients with history of epilepsy versus 11.9% for patients without epilepsy
      (P=0.014). Patients with epilepsy had a significantly lower rate of presentation
      with ventricular tachycardia/ventricular fibrillation as opposed to pulseless
      electrical activity/asystole (epilepsy, 26%; no epilepsy, 44%; P=0.002), despite
      nearly identical response times. CONCLUSIONS: In the majority (66%) of epilepsy
      patients, there was no relationship between seizure and SCA, implying that SCA in
      epilepsy patients often may not involve seizure as a trigger. The significantly
      worse rate of survival from SCA in epilepsy patients warrants urgent
      investigation.

PMID- 23965298
TI  - A primer on receiver operating characteristic analysis and diagnostic efficiency
      statistics for pediatric psychology: we are ready to ROC.
AB  - OBJECTIVE: To offer a practical demonstration of receiver operating
      characteristic (ROC) analyses, diagnostic efficiency statistics, and their
      application to clinical decision making using a popular parent checklist to
      assess for potential mood disorder. METHOD: Secondary analyses of data from 589
      families seeking outpatient mental health services, completing the Child Behavior
      Checklist and semi-structured diagnostic interviews. RESULTS: Internalizing
      Problems raw scores discriminated mood disorders significantly better than did
      age- and gender-normed T scores, or an Affective Problems score. Internalizing
      scores <8 had a diagnostic likelihood ratio <0.3, and scores >30 had a diagnostic
      likelihood ratio of 7.4. CONCLUSIONS: This study illustrates a series of steps in
      defining a clinical problem, operationalizing it, selecting a valid study design,
      and using ROC analyses to generate statistics that support clinical decisions.
      The ROC framework offers important advantages for clinical interpretation.
      Appendices include sample scripts using SPSS and R to check assumptions and
      conduct ROC analyses.

PMID- 23965299
TI  - Puerarin promotes osteogenesis and inhibits adipogenesis in vitro.
AB  - BACKGROUND: Puerarin (daidzein 8-C-glucoside) has potential on preventing
      osteoporosis. This study aims to investigate the effects of puerarin on
      osteogenesis and adipogenesis in vitro. METHODS: CCK-8 assay, alkaline
      phosphatase (ALP) activity and Alizarin Red S were used to measure the effects of
      puerarin on proliferation, osteoblastic differentiation, and mineralization in
      osteoblast-like MC3T3-E1 cells. The effects of puerarin on adipogenesis were
      measured by Oil Red O staining and intracellular triglyceride level in
      preadipocyte 3T3-L1 cells. The mRNA and protein levels of osteogenesis- and
      adiopogenesis-related factors were detected by qRT-PCR and western blot,
      respectively. Further, the secreted osteocalcin levels and nuclear translocation
      of beta-catenin were detected by ELISA and immunofluorescence assay,
      respectively. RESULTS: As to osteogenesis, puerarin could stimulate proliferation
      (1 MUM, P = 0.012; 10 MUM, P = 0.015; 20 MUM, P = 0.050), ALP activity (20 MUM, P
      = 0.008) and calcium nodule formation (20 MUM, P = 0.011) in a dose-dependent
      manner. Puerarin (20 MUM) promoted osteocalcin secretion (P = 0.004) and the
      protein expression of both osteopontin (P = 0.001) and osteoprotegerin (P =
      0.003). As to adipogenesis, puerarin suppressed adipocytes formation and
      intracellular triglyceride level (P = 0.001). In addition, puerarin (20 MUM)
      decreased the mRNA and protein levels of CCAAT/enhancer binding protein alpha (P
      = 0.001, P = 0.002), proliferator-activated receptor gamma (P = 0.005, P =
      0.003), and adipocyte lipid-binding protein 4 (P = 0.001, P = 0.001). Moreover,
      phosphorylation of AKT1-Ser437 (10 MUM, P = 0.003; 20 MUM, P = 0.007) and GSK
      Ser9 (10 MUM, P = 0.005; 20 MUM, P = 0.003), and the nuclear translocation of
      beta-catenin (10 MUM, P = 0.006; 10 MUM, P = 0.002) were increased in 3T3-L1
      cells treated by puerarin. CONCLUSION: Puerarin promoted osteogenesis and
      inhibited adipogenesis in vivo, and Akt/GSK-3beta/beta-catenin signaling pathway
      was involved in the suppression of adipogenesis.

PMID- 23965301
TI  - Clinical effect of acupuncture on cervical spondylotic radiculopathy: results of
      a case series.
AB  - OBJECTIVE: To observe the effectiveness of acupuncture applied to the cervical
      region of patients with upper extremity radicular symptoms due to cervical
      spondylotic radiculopathy (CSR). METHODS: 15 subjects diagnosed with CSR and with
      upper extremity pain and/or paraesthesiae for 13.1+/-18.0 months were selected.
      The 15 patients had 16 affected limbs and scored a total of 17 symptom scores of
      pain and/or paraesthesiae. All patients were treated with acupuncture once a week
      for 4 weeks at up to 10 sites in the cervical paraspinal region centred on the
      affected area. The severity of the symptoms was recorded using a visual analogue
      scale (VAS) and functional evaluation was conducted using a Neck Disability Index
      (NDI). RESULTS: A significant reduction over time was seen for both mean VAS
      (p<0.0001) and NDI (p<0.0001). Changes were still significant at 4-week follow
      up. A 50% reduction in symptoms was scored for 15 of the 17 symptoms scored.
      CONCLUSIONS: Favourable results were seen in nearly 90% of cases. These results
      show that acupuncture treatment to the cervical region may be effective as a
      conservative therapy for treating CSR.

PMID- 23965300
TI  - Personalized exercise for adolescents with diabetes or obesity.
AB  - OBJECTIVE: This study examined adherence to a personalized, community-based
      exercise intervention by sedentary adolescents with type 1 or type 2 diabetes or
      those with obesity. RESEARCH DESIGN AND METHODS: We conducted a pretest-posttest
      investigation to explore the application of an individualized exercise
      prescription based upon current fitness level for 39 adolescents (20 with type 1
      diabetes, 9 with type 2 diabetes, and 10 obese) over 16 weeks in community
      settings. Subjects were recruited from a university-based pediatric endocrinology
      clinic in the southwestern United States. Adherence to the exercise prescription
      was monitored using accelerometers over the entire intervention period. RESULTS:
      Moderate-to-vigorous physical activity (MVPA) levels significantly increased over
      sedentary baseline values (p < .001), but the average of 42.5 +/- 22.1 min/day of
      MVPA determined at the end of the study was still less than the recommended 60
      min/day. Perceptions of health were significantly increased for the total group
      following the intervention (p = .008). For those with type 1 diabetes, there was
      a significant association between MVPA duration and percentage change in HbA1c (r
      = -.526, p = .02). CONCLUSIONS: Recruitment and retention of adolescent
      participation in daily exercise is challenging. Personalized approaches that
      include adolescent choices with family support and ongoing motivation can improve
      individual exercise adherence and a sense of personal health.

PMID- 23965302
TI  - Acupuncture and moxibustion treatment for hypersexuality in a patient who was
      uraemic: a case report.
AB  - This report concerns a case that shows the apparent successful use of acupuncture
      and moxibustion in treating hypersexuality. The patient was a 60-year-old Chinese
      woman with a history of uraemia for 4 years and hypersexuality for 7 months, the
      latter being a rare condition. The presenting symptoms were persistent sexual
      desires and fantasies, in addition to being irritated when her continuous sexual
      urges could not be satisfied. In order to control her sexual desire the patient
      had tried almost all viable therapeutic methods, including use of sedatives, but
      the symptoms could not be mitigated any further even after consulting eight
      different hospital departments. However, after 10 days of acupuncture and
      moxibustion, all her symptoms related to the problem were resolved. A year later,
      she presented with a slight relapse with similar symptoms and was again treated
      with acupuncture and moxibustion, with subsequent resolution of symptoms. Over
      the following 2 years, such symptoms have not recurred. Based on the findings
      from this case, we conclude that use of acupuncture and moxibustion may be an
      effective treatment for hypersexuality in clinical practice. 

PMID- 23965303
TI  - Research practices that can prevent an inflation of false-positive rates.
AB  - Recent studies have indicated that research practices in psychology may be
      susceptible to factors that increase false-positive rates, raising concerns about
      the possible prevalence of false-positive findings. The present article discusses
      several practices that may run counter to the inflation of false-positive rates.
      Taking these practices into account would lead to a more balanced view on the
      false-positive issue. Specifically, we argue that an inflation of false-positive
      rates would diminish, sometimes to a substantial degree, when researchers (a)
      have explicit a priori theoretical hypotheses, (b) include multiple replication
      studies in a single paper, and (c) collect additional data based on observed
      results. We report findings from simulation studies and statistical evidence that
      support these arguments. Being aware of these preventive factors allows
      researchers not to overestimate the pervasiveness of false-positives in
      psychology and to gauge the susceptibility of a paper to possible false-positives
      in practical and fair ways. 

PMID- 23965304
TI  - Dicodon monitoring of protein synthesis (DiCoMPS) reveals levels of synthesis of
      a viral protein in single cells.
AB  - The current report represents a further advancement of our previously reported
      technology termed Fluorescent transfer RNA (tRNA) for Translation Monitoring
      (FtTM), for monitoring of active global protein synthesis sites in single live
      cells. FtTM measures Forster resonance energy transfer (FRET) signals, generated
      when fluorescent tRNAs (fl-tRNAs), separately labeled as a FRET pair, occupy
      adjacent sites on the ribosome. The current technology, termed DiCodon Monitoring
      of Protein Synthesis (DiCoMPS), was developed for monitoring active synthesis of
      a specific protein. In DiCoMPS, specific fl-tRNA pair combinations are selected
      for transfection, based on the degree of enrichment of a dicodon sequence to
      which they bind in the mRNA of interest, relative to the background transcriptome
      of the cell in which the assay is performed. In this study, we used cells
      infected with the Epizootic Hemorrhagic Disease Virus 2-Ibaraki and measured,
      through DiCoMPS, the synthesis of the viral non-structural protein 3 (NS3), which
      is enriched in the AUA:AUA dicodon. fl-tRNA(Ile)UAU-generated FRET signals were
      specifically enhanced in infected cells, increased in the course of infection and
      were diminished on siRNA-mediated knockdown of NS3. Our results establish an
      experimental approach for the single-cell measurement of the levels of synthesis
      of a specific viral protein. 

PMID- 23965305
TI  - Structure of an 'open' clamp type II topoisomerase-DNA complex provides a
      mechanism for DNA capture and transport.
AB  - Type II topoisomerases regulate DNA supercoiling and chromosome segregation. They
      act as ATP-operated clamps that capture a DNA duplex and pass it through a
      transient DNA break in a second DNA segment via the sequential opening and
      closure of ATPase-, G-DNA- and C-gates. Here, we present the first 'open clamp'
      structures of a 3-gate topoisomerase II-DNA complex, the seminal complex engaged
      in DNA recognition and capture. A high-resolution structure was solved for a
      (full-length ParE-ParC55)2 dimer of Streptococcus pneumoniae topoisomerase IV
      bound to two DNA molecules: a closed DNA gate in a B-A-B form double-helical
      conformation and a second B-form duplex associated with closed C-gate helices at
      a novel site neighbouring the catalytically important beta-pinwheel DNA-binding
      domain. The protein N gate is present in an 'arms-wide-open' state with the
      undimerized N-terminal ParE ATPase domains connected to TOPRIM domains via a
      flexible joint and folded back allowing ready access both for gate and
      transported DNA segments and cleavage-stabilizing antibacterial drugs. The
      structure shows the molecular conformations of all three gates at 3.7 A, the
      highest resolution achieved for the full complex to date, and illuminates the
      mechanism of DNA capture and transport by a type II topoisomerase. 

PMID- 23965306
TI  - DAZAP1 regulates the splicing of Crem, Crisp2 and Pot1a transcripts.
AB  - Deleted in Azoospermia Associated Protein 1 (DAZAP1) is a ubiquitous
      heterogeneous nuclear ribonucleoprotein (hnRNP) that is expressed abundantly in
      the testis. DAZAP1 deficiency in mice results in growth retardation and
      spermatogenic arrest. Previous reports on DAZAP1's binding to several naturally
      occurring splicing mutations support a role for DAZAP1 in RNA splicing. To
      elucidate the biological function(s) of DAZAP1 and to search for its natural RNA
      substrates, we used microarrays to compare the expression profiles and exon
      usages of wild-type and Dazap1 mutant testes and identified three genes (Crem,
      Crisp2 and Pot1a) with aberrant RNA splicing in the mutant testes. We further
      demonstrated that DAZAP1, but not DAZAP1 mutant proteins, promoted the inclusion
      of Crem exon 4, Crisp2 exon 9 and Pot1a exon 4 in splicing reporter transcripts
      in cultured cells. Additional studies on the binding of DAZAP1 to the exons and
      their flanking intronic sequences and the effects of minigene deletions on exon
      inclusion identified regulatory regions in Crem intron 3, Crisp2 intron 9 and
      Pot1a intron 4 where DAZAP1 bound and regulated splicing. Aberrant splicing of
      the Pot1a gene, which encodes an essential protein that protects telomere
      integrity, may partially account for the growth retardation phenotype of DAZAP1
      deficient mice. 

PMID- 23965307
TI  - Structural insight into LexA-RecA* interaction.
AB  - RecA protein is a hallmark for the bacterial response to insults inflicted on
      DNA. It catalyzes the strand exchange step of homologous recombination and
      stimulates self-inactivation of the LexA transcriptional repressor. Importantly,
      by these activities, RecA contributes to the antibiotic resistance of bacteria.
      An original way to decrease the acquisition of antibiotic resistance would be to
      block RecA association with LexA. To engineer inhibitors of LexA-RecA complex
      formation, we have mapped the interaction area between LexA and active RecA-ssDNA
      filament (RecA*) and generated a three-dimensional model of the complex. The
      model revealed that one subunit of the LexA dimer wedges into a deep helical
      groove of RecA*, forming multiple interaction sites along seven consecutive RecA
      protomers. Based on the model, we predicted that LexA in its DNA-binding
      conformation also forms a complex with RecA* and that the operator DNA sterically
      precludes interaction with RecA*, which guides the induction of SOS gene
      expression. Moreover, the model shows that besides the catalytic C-terminal
      domain of LexA, its N-terminal DNA-binding domain also interacts with RecA*.
      Because all the model-based predictions have been confirmed experimentally, the
      presented model offers a validated insight into the critical step of the
      bacterial DNA damage response. 

PMID- 23965308
TI  - The sequencing bias relaxed characteristics of Hi-C derived data and implications
      for chromatin 3D modeling.
AB  - The 3D chromatin structure modeling by chromatin interactions derived from Hi-C
      experiments is significantly challenged by the intrinsic sequencing biases in
      these experiments. Conventional modeling methods only focus on the bias among
      different chromatin regions within the same experiment but neglect the bias
      arising from different experimental sequencing depth. We now show that the
      regional interaction bias is tightly coupled with the sequencing depth, and we
      further identify a chromatin structure parameter as the inherent characteristics
      of Hi-C derived data for chromatin regions. Then we present an approach for
      chromatin structure prediction capable of relaxing both kinds of sequencing
      biases by using this identified parameter. This method is validated by intra and
      inter cell-line comparisons among various chromatin regions for four human cell
      lines (K562, GM12878, IMR90 and H1hESC), which shows that the openness of
      chromatin region is well correlated with chromatin function. This method has been
      executed by an automatic pipeline (AutoChrom3D) and thus can be conveniently
      used. 

PMID- 23965309
TI  - "Chemo brain"--is cancer survivorship related to later-life cognition? Findings
      from the health and retirement study.
AB  - OBJECTIVE: Studies have shown a correlation between cancer and cognition referred
      to as "chemo brain." This study investigated the relationship between cancer and
      later-life cognition using nationally representative data. METHOD: Analysis of
      the 2006 Health and Retirement Study investigated the (a) effects of cancer
      survivorship on the total cognition score using linear regression in adults age
      65+ (n = 9,814) and (b) the effects of cancer treatment on the total recall index
      using linear regression in adults age 50+ (n = 657). RESULTS: Total cognition
      score is not associated with cancer survivorship. The association between long
      term cancer survivorship and cognition score was significant (p < .05; b = .276).
      Total recall index is not associated with chemotherapy. DISCUSSION: These results
      support other research suggesting that chemo brain may be biased by expectation
      as well as favored by research that relies upon self-reported cognitive measures
      versus cognitive testing. The study was limited by the cross-sectional design.

PMID- 23965311
TI  - The use of radio-collars for monitoring wildlife diseases: a case study from
      Iberian ibex affected by Sarcoptes scabiei in Sierra Nevada, Spain.
AB  - BACKGROUND: Wildlife radio tracking has gained popularity during the recent past.
      Ecologists and conservationists use radio-collars for different purposes: animal
      movement monitoring, home range, productivity, population estimation, behaviour,
      habitat use, survival, and predator-prey interaction, among others. The aim of
      our present study is to highlight the application of radio-collars for wildlife
      diseases monitoring. The spread of wildlife diseases and the efficacy of
      management actions for controlling them propose serious challenges for ecologists
      and conservationists, since it is difficult to re-capture (or simply observe) the
      same animal in pre-determined temporal interval, but such difficulty is overcome
      by the use of gps-gsm radio collars. METHODS: In the present study we report, for
      the first time to our knowledge, the use of radio-collars in the monitoring of
      Iberian ibex affected by Sarcoptes scabiei in Sierra Nevada mountain range,
      Spain. Twenty-five moderate or slightly mangy animals were radio-collared between
      2006 and 2013. RESULTS: The radio-collars allowed us to confirm the presence of
      resistance to S. scabiei within Iberian ibex population. Twenty (80%) of the
      collared animals recovered totally from mange, while the disease progressed in
      the other five Iberian ibex (20% of the collared animals) and the animals died.
      The average estimated recovery time of the resistant animals was 245 +/- 277
      days, and the estimated average survival time of the non-resistant Iberian ibex
      was 121 +/- 71 days. Non-resistant animals survived at least 100 days, while all
      of them died with less than 200 days. Sixty per cent of the resistant animals
      were recovered with less than 200 days. CONCLUSIONS: We report, for the first
      time, the successful use of radio collars for wildlife diseases monitoring using
      Iberian ibex/S. scabiei as a model. By using radio collars we documented that
      most of the Sarcoptes-infected Iberian ibex are resistant to this disease, and we
      estimated the average time for Iberian ibex recovering from mange infection and
      the average survival time of the non-resistant ones. We expect wider use of radio
      collars for wild animals diseases monitoring, affected/not-affected animals
      interaction, and treatment efficacy, among others.

PMID- 23965310
TI  - Life-space mobility predicts nursing home admission over 6 years.
AB  - OBJECTIVE: To explore the association between baseline life-space mobility and
      nursing home (NH) admission among community-dwelling older adults over 6 years.
      METHODS: Using data from a prospective, observational cohort study consisting of
      a random sample of 1,000 Medicare beneficiaries >= 65 years of age stratified by
      race (African American and non-Hispanic White), sex, and rural/urban residence.
      Baseline life-space mobility was assessed during in-home interviews. Participants
      were contacted by telephone every 6 months to ascertain NH admissions, Life-Space
      Assessment (LSA) scores, and vital status (living or deceased). Using
      multivariate logistic regression, the significance and independence of the
      relationship of life-space mobility with NH admission were examined. RESULTS:
      Over 6 years, the odds of NH admission increased 2% for every one point lower
      baseline life-space score independent of previously recognized risk factors.
      DISCUSSION: The LSA may be a useful tool to identify older adults at risk of NH
      admission.

PMID- 23965313
TI  - [Circumferential resection margin in the modern treatment of rectal cancer].
AB  - INTRODUCTION: In the last decades, the assessment of circumferential resection
      margin (CRM) has gained enormous importance in the management of patients with
      rectal carcinoma, not only in predicting the prognosis, but also in precise
      cancer staging, in multimodal treatment indications and in quality assessment of
      provided care. METHODS: The authors present a review article containing CRM
      definition, describing the technique of CRM assessment, the effect of CRM status
      on the prognosis and quality of provided therapy. CRM assessment in the context
      of a multidisciplinary team is especially emphasised. The aspect of CRM has to be
      considered by the radiologist during cancer staging, the surgeon in the course of
      the operation, the pathologist during precise macroscopic and histopathological
      specimen evaluation, and the oncologist when deciding on neoadjuvant/adjuvant
      therapy administration. CONCLUSION: CRM nowadays represents a fundamental aspect
      in modern treatment of patients with rectal carcinoma. The introduction of CRM
      assessment into clinical practice has lead to more precise staging, better
      multimodal therapy indications, more precise surgical technique (total mesorectal
      excision), an increased rate of sphincter-saving resections, lowered local
      recurrence rates and improved patient survival.

PMID- 23965312
TI  - Rule-based regulatory and metabolic model for Quorum sensing in P. aeruginosa.
AB  - BACKGROUND: In the pathogen P. aeruginosa, the formation of virulence factors is
      regulated via Quorum sensing signaling pathways. Due to the increasing number of
      strains that are resistant to antibiotics, there is a high interest to develop
      novel antiinfectives. In the combat of resistant bacteria, selective blockade of
      the bacterial cell-to-cell communication (Quorum sensing) has gained special
      interest as anti-virulence strategy. Here, we modeled the las, rhl, and pqs
      Quorum sensing systems by a multi-level logical approach to analyze how enzyme
      inhibitors and receptor antagonists effect the formation of autoinducers and
      virulence factors. RESULTS: Our rule-based simulations fulfill the behavior
      expected from literature considering the external level of autoinducers. In the
      presence of PqsBCD inhibitors, the external HHQ and PQS levels are indeed clearly
      reduced. The magnitude of this effect strongly depends on the inhibition level.
      However, it seems that the pyocyanin pathway is incomplete. CONCLUSIONS: To match
      experimental observations we suggest a modified network topology in which PqsE
      and PqsR acts as receptors and an autoinducer as ligand that up-regulate
      pyocyanin in a concerted manner. While the PQS biosynthesis is more appropriate
      as target to inhibit the HHQ and PQS formation, blocking the receptor PqsR that
      regulates the biosynthesis reduces the pyocyanin level stronger.

PMID- 23965315
TI  - [Not Available].

PMID- 23965314
TI  - [The radicality of surgical resection in rectal cancer. Analysis of factors
      associated with incomplete mesorectal excision].
AB  - INTRODUCTION: Circumferential resection margin (pCRM) and the completeness of
      mesorectal excision (ME) are two independent prognostic factors significantly
      associated with the radicality of surgical treatment. Positive pCRM and
      incomplete mesorectal excision are associated with a significantly higher
      incidence of local recurrence and worse patient prognosis. The aim of this
      article is to analyze the risk factors associated with incomplete mesorectal
      excision. MATERIAL AND METHODS: Patients operated on at the Department of
      Surgery, University Hospital Hradec Kralove between January 2011 and February
      2013 were included in the study. The patients data were prospectively collected
      and entered in the Dg C20 registry. The following factors were analyzed: sex,
      age, BMI, cN, pT, clinical stage, the involved segment of the rectum, neoadjuvant
      therapy, circumferential tumour location, the type of surgical approach and the
      type of surgery. RESULTS: 168 patients were operated on during the above period.
      9 (5.3%) palliative stomas and 159 (94.6%) resection procedures were performed in
      this group of 168 patients. 7 (4.4%) patients were excluded because the quality
      of excision was not assessed in them. 114 (75%) resections, including 5
      intersphincteric resections, were performed in the group of the remaining 152
      patients. 10 (7%) were Hartmanns procedures a 28 (18%) were amputation
      procedures. Out of 152 procedures, 69 (45%) were performed laparoscopically.
      Positive (y)pCRO was recorded in 26 (17%) patients, predominantly after
      abdominoperineal resection (APR) - 11 out of 27 (41%), and Hartmanns operation -
      6 out of 10 (60%). Incomplete ME was observed in 45 patients (30%), complete ME
      in 81 patients (53%) and partially complete in 26 patients (17%). Univariate
      analysis confirmed statistically significant factors associated with incomplete
      mesorectal excision: (y)pT (P = 0.00027), type of surgery (P = 0.00001) and
      tumour location (P = 0.00001). Multivariate analysis then confirmed two
      independent prognostic factors associated with incomplete mesorectal excision. It
      was the location of the tumour in the distal third of the rectum and the (y)pT
      stage of the tumour. CONCLUSION: Distal rectum tumor location and higher (y)pT
      are associated with a higher risk of incomplete mesorectal excision with worse
      patient prognosis.

PMID- 23965316
TI  - [Rectal cancer within 10 cm. Comparison of the radicality of laparoscopic and
      open surgical techniques with regard to the circumferential resection margin and
      the completeness of mesorectal excision].
AB  - INTRODUCTION: The issue of achieving radical circumferential margin in
      laparoscopic rectal surgery has not yet been satisfactorily clarified. In this
      paper we have focused on circumferential margin assessment and the quality of the
      mesorectal excision, comparing laparoscopic and open resection for cancer of the
      middle and lower rectum. MATERIAL AND METHODS: The results of surgical procedures
      for middle and low rectal cancer were analysed. All the interventions were
      performed at the Department of Surgery, Teaching Hospital in Hradec Kralove,
      during the period from January 2011 to December 2012. The data were prospectively
      collected and entered in the Rectal Cancer Registry. Age, gender, BMI, tumour
      localisation and topography, the clinical stage, preoperative chemoradiotherapy
      and response to it, the type of surgery, distal and circumferential margin
      characteristics, mesorectal excision quality, pT and pN were compared for
      laparoscopic and open surgery. RESULTS: A total of 161 patients were operated on
      for rectal cancer during the abovementioned period. 94 patients were included in
      the trial following selection. Laparoscopy was used in 40 patients and open
      surgery in 54 patients. Laparoscopic approach was performed in 33 (82.5%) low
      anterior resections (including four intersphincteric resections), 6 (15%)
      abdominoperineal amputations and 1 (2.5%) Hartmanns procedure. Open surgery was
      used for 26 (48.1%) low anterior resections, 21 (38.9%) APR and 7 (13%) Hartmanns
      procedures. Complete mesorectal excision was achieved in 45% of the laparoscopic
      resections vs. 46.3% of open resections. Nearly complete excision was performed
      in 22.5% and 11.1%, respectively. Finally, incomplete excision was described in
      30% vs. 38.9%. No available data for TME was detected in three patients. The
      differences in TME were not statistically significant. Positive circumferential
      margin was found in 5 (12.5%) patients in the laparoscopy group; on the contrary,
      in the group undergoing open surgery, pCRO+ was found in 15 (27.8%) patients.
      Here, too, the results were not statistically significant. When patients without
      preoperative chemoradiotherapy were excluded, the relationship between ypCRM in
      the laparoscopy and open surgery group was on the border of statistical
      significance (Fischer=0.0556). CONCLUSION: As has been shown in our trial, the
      outcomes of laparoscopic and open approach in rectal cancer treatment are very
      similar. Particularly, mesorectal excision quality and negative CRM results have
      proven that the laparoscopic technique is safe and comparable to open surgery in
      rectal cancer treatment.

PMID- 23965317
TI  - [Anatomic-surgical study of intercostobrachial nerve (ICBN) course in axilla
      during I. and II. level of axilla clearance in breast cancer and malignant
      melanoma].
AB  - INTRODUCTION: The aim of this paper is to offer results of anatomic study of
      axillary course of intercostobrachial nerve (ICBN) and the effort of its saving
      in primary axilla clearance (PE), secondary clearance (SE) after previous
      positive sentinel nodes detection (SLN) and in re-clearance (RE) after previous
      axilla clearance in breast cancer and malignant melanoma. The correlation between
      possibility of ICBN saving and anatomic variant of ICBN and type of previous
      surgery was observed. MATERIAL AND METHODS: A total of 113 surgeries with the
      effort of description and preservation of ICBN were done between September 2007
      and August 2011. Patients were divided into three groups according to type of
      surgery: primary clearance (PE), secondary clearance (SE) and re-clearance (RE).
      Results have been statistically tested using licensed statistical software
      Statgraphics. RESULTS: ICBN was found in 107 patients (94.7%), it wasnt found in
      six cases. There were eight different types of ICBN branching. Two most frequent
      variants formed majority of cases - 87 out of 107 (81.3%). The successful
      preservation of intact ICBN was in 86 patients (76.1%). ICBN was interrupted or
      not found in 10 patients (8.8%), partial injury of ICBN branches was detected in
      17 cases (15.0%). If the most frequent variant of ICBN branching was present, the
      nerve was not injured in 42 out of 45 cases (93.3%). Statistical testing showed
      that non-standard anatomical branches are associated with higher risk of
      perioperative injury. The risk of injury was lowest in PE (21.6%) and the highest
      in RE (42.9%). The difference wasnt statistically significant because of low
      number of re-clearance cases in our study. CONCLUSION: The anatomy of ICBN in
      axilla is variable. The standard variant of ICBN course is the most frequent (the
      trunk coming out of second intercostal space; no branches in axillary course). If
      other variants are present, there is significantly higher risk of perioperative
      injury. ICBN preservation is possible also after previous axilla clearance.
      Preparation is more difficult and the risk of injury is increasing with the
      degree of previous surgery radicality.

PMID- 23965318
TI  - [Incarcerated De Garengeots hernia complicated by gangrenous appendicitis].
AB  - Femoral hernias account for only about 0.7% of all operated hernias and are
      rather infrequent among male patients. By contrast, acute appendicitis is one of
      the most frequent diagnoses in surgery requiring urgent operation. The authors
      present one of the rare cases in which both these diagnoses occur together - De
      Garengeots hernia. Incarcerated femoral hernia with acute appendicitis is
      diagnosed preoperatively only sporadically. Imaging methods can help in the
      diagnosis, but often the final diagnosis, and especially the final solution, is
      brought about only by surgical intervention.

PMID- 23965319
TI  - [Reexpansion pulmonary oedema after drainage of a long-term spontaneous
      pneumothorax - a case report].
AB  - Reexpansion pulmonary oedema is a rare but possibly lethal complication of
      thoracic drainage for pneumothorax. Morbidity and mortality of this complication
      remains high (up to 20% of lethal cases) and as such deserves our attention. We
      report a case of ipsilateral left-sided pulmonary oedema following chest tube
      insertion in a 42-year-old male patient with spontaneous pneumothorax.
      Pneumothorax can be expected to last for up to 3 weeks (from the first
      presentation of sudden dyspnoea and chest pain). The pathophysiology of this lung
      affection has not yet been completely elucidated; the crucial role is probably
      played by damage to the endothelium which is followed by increased endothelial
      permeability during ischemia-reperfusion injury in a rapidly reexpanding lung.
      The main risk factors for the development of RPE are young age (the younger the
      patient, the higher the risk), the female sex, the degree of lung collapse, a
      pneumothorax that lasts more than 24 hours, a reexpansion of the lung in less
      than ten minutes, the use of a suction system, and - in cases of a pleural
      effusion - an evacuation volume of more than 2000 ml. Although in patients with
      these risk factors the administration of initial negative pressure should be
      avoided, this procedure remains common practice in pneumothorax treatment in the
      Czech Republic. Thoracic surgeons are more likely to use the suction system than
      pulmonologists (70% versus 52%). RPE manifestation ranges from benign clinical
      course (patients are free of complaints with only pathological chest radiography
      findings) to potentially lethal rapid respiratory failure with circulatory shock.
      Most patients develop RPE within 1 hour of expansion and the ipsilateral lung is
      affected. Only rarely can pulmonary oedema be bilateral, or in the contra-lateral
      lung. Treatment of RPE is supportive and depends on the individual patients
      condition, ranging from mere monitoring to mechanical ventilation for serious
      cases. Positive pressure mechanical ventilation and the utilization of positive
      end-expiratory pressure (PEEP) remains the gold standard of treatment.

PMID- 23965321
TI  - Oxytocin effects on neural correlates of self-referential processing.
AB  - Oxytocin (OT) influences how humans process information about others. Whether OT
      affects the processing of information about oneself remains unknown. Using a
      double-blind, placebo-controlled within-subject design, we recorded event-related
      potentials (ERPs) from adults during trait judgments about oneself and a
      celebrity and during judgments on word valence, after intranasal OT or placebo
      administration. We found that OT vs. placebo treatment reduced the differential
      amplitudes of a fronto-central positivity at 220-280 ms (P2) during self- vs.
      valence-judgments. OT vs. placebo treatment tended to reduce the differential
      amplitude of a late positive potential at 520-1000 ms (LPP) during self-judgments
      but to increase the differential LPP amplitude during other-judgments. OT effects
      on the differential P2 and LPP amplitudes to self- vs. celebrity-judgments were
      positively correlated with a measure of interdependence of self-construals. Thus
      OT modulates the neural correlates of self-referential processing and this effect
      varies as a function of interdependence.

PMID- 23965322
TI  - Compliance to treatment in elderly dysphagic patients: potential benefits of
      alternative dosage forms.
AB  - Dysphagia in elderly patients significantly impacts nutrition, pharmacotherapy,
      and quality of life. Dysphagic patients, especially those with contributing
      degeneratve neurological disorders, present unique challenges to their families,
      caregivers, and healthcare professionals. Pharmacists have a key role in
      proactively inquiring about dysphagia, ensuring safety, increasing compliance,
      and ultimately improving clinical outcomes through medication regimen assessment
      in this rapidly growing patient population. 

PMID- 23965323
TI  - Autologous eye drops for the treatment of dry eye and neurotrophic keratitis.
AB  - Tears-which contain fibronectin, growth facors, and vitamins that support the
      migration, proliferation, and differentiation of the conjunctival and corneal
      epithelium-nourish, protect, and refresh the eye. An inadequate tear film
      produces a variety of symptoms (ocular irritation, itching, burning, eye strain
      or fatigue, photophobia, a foreign-body sensation, a sharp stabbing pain, blurred
      vision) that wax and wane in intensity and are characteristic of disorders such
      as dry eye (keratoconjunctivitis sicca) and neurotrophic keratitis. In patients
      for whom commercially manufactured eye drops fail to provide relief from the
      symptoms of those conditions, autologous serum eye drops (plasma eye drops, serum
      eye drops) have proven very effective. In this report, we examine the present
      case studies that reveal the efects of autologous serum eye drops on the signs
      and symptoms of both dry eye and neurotrophic keratitis. A procedure for
      preparing autologous eye drops is included. 

PMID- 23965324
TI  - Urinary Deoxypyridinoline Level Reveals Bone Resorption, Predicts Fracture Risk,
      And Enhances the Results of Dual Energy X-ray Absorptiometry.
AB  - Bone loss leads to an increased incidence of fracture and is associated with the
      development of osteoporosis, which can strike people of any age and afflicts 10
      million individuals in the U.S. today. Research indicates that osteoporosis
      causes more than 1.5 million fractures annually, including approximately 300,000
      fractures at other sites. Early detection of bone loss (resorption), like that
      revealed by a combination of dual energy X-ray absorptiometry and monitoring the
      level of deoxypyridinoline in urine, provides the most complete picture of long
      term and short-term bone health. In this reports, we examine the effects of
      increased bone resorption and various methods of testing for bone loss, present
      findings from the literature on the effects of and monitorying for bone
      resorption, and profile individuals most likely to benefit from testing for a
      decrease in bone mass. 

PMID- 23965325
TI  - Low testosterone in older men: a discussion and review of literature on health
      consequences of hypogonadism in the aging male.
AB  - We have learned a great deal about testosterone over a long period of time and
      are familiar with its role in sexual function, libido, muscle strength/tone,
      erythropoiesis, and bone mineral density. What we are less familiar with are the
      consequences of low testosterone-hypogonadism-as it relates to the Metabolic
      Syndrome, and the strong association with diabetes and cardiovascular disease. It
      is clear that many medical researchers have taken a strong interest and are
      finding significant data in hypogonadism as it affects certain comorbid
      conditions. 

PMID- 23965326
TI  - An overview of United States pharmacopeia chapter 795 and american society of
      health-system pharmacists guidelines for nonsterile compounding.
AB  - Hospital pharmacy departments should be compliant with the standards of United
      States Pharmacopeia Chapter 795. In order to remain compliant, small hospitals
      and institutions must properly train their staff to ensure that their compounding
      procedures and the resultant preparations are in compliance with the standards in
      Chapter 795. For reasons outlined in this article, it is more challenging for
      large hospitals and institutions to remain compliant; they require a specialized
      staff that must keep all compounding personnel updated with the constant changes
      in compounding practices and standards outlined by the United States
      Pharmacopeial Convention. This article summarizes Chapter 795 on Pharmaceutical
      Compounding Nonsterile Preparations, key points in the American Society of Health
      System Pharmacists TAB guidelines on compounding nonsterile products in
      pharmacies, and author recommendations on applying these standards and guidelines
      in hospital pharmacy departments. 

PMID- 23965327
TI  - Setting up a national system of compounding pharmacies: preventing error,
      assuring quality, building trust.
AB  - Influencing the drawing of future legislation, gaining the confidence of
      consumers, prescribers, and government; and enhancing the communication with the
      medical profession are among the major upcoming challenges for compounding
      pharmacists worldwide. In our systematic effort to prevent eror and improve
      quality, we have learned that guidance is our main ally. When the Brazilian
      National Health Agency issued legislation that had a major impact on operating
      costs for compounding businesses, the Brazilian National Health Agency issued
      legislation that had major impact on operating costs for compounding businesses,
      the Brazilian National Association of Compounding Pharmacies, a nongovernmental
      organization, set out to tackle the many deadlocks resulting from the
      legislation. With the support of compounding pharmacists, the association has
      been able to develop and implement a National System for the Monitoring and
      Improvement of Compounding Practices, a process-focused system. Custom-made,
      individualized drugs are necessary for providing the best treatment, and
      compounding pharmacies must be viewed and act as partners for health. 

PMID- 23965328
TI  - Applications and sterility of autologous serum eye drops.
AB  - Severe dry eye syndrome can adversely affect a patient's quality of life. When
      preservative-free artificial tear solutions are not adequate to reduce symptons,
      the patient's own serum can be compounded into eye drops that improve the ocular
      surface. The aim of our study was to test the sterility of autologous serum eye
      drops in refrigerator conditions for up to 30 days and in freezer conditions for
      up to 180 days. It was determined that sterility was maintained throughout this
      period. 

PMID- 23965329
TI  - Basics of compounding: considerations for implementing United States pharmacopeia
      chapter 797 pharmaceutical compounding-sterile preparations, part 16: suggested
      standard operating procedures.
AB  - The standard operating procedures suggested in this article are presented to
      compounding pharmacies to ensure the quality of the environment in which a CSP is
      prepared. Since United States Pharmacopeia Chapter 797 provides minimum
      standards, each facility should aim for best practice gold standard. The standard
      operating procedures should be tailored to meet the expectations and design of
      each facility. Compounding personnel are expected to know and understand each
      standard operating procedure to allow for complete execution of the procedures. 

PMID- 23965330
TI  - Stability of preoperative cataract surgery gel in polycarbonate syringes.
AB  - The stability of preoperative cataract surgery gel packaged in 1-mL polycarbonate
      syringes, stored protected from light under controlled temperatures for a period
      of 60 days, was studied. Preoperative cataract surgery gel is a mixture of
      cyclopentolate hydrochloride 0.51 mg/mL, phenylephrine hydrochloride 5.1 mg/mL,
      and tropicamide 0.51/mL in preservative-free lidocaine hydrochloride 2% gel.
      Stability was defined as the maintenance of initial physical and chemical
      charactereistics during storage under controlled ambient (25 deg C/60% relative
      humitidty) or refrigerated (2 deg C to 4 deg C) conditions. Evaluation parameters
      were appearance, pH,sterility, endotoxin level, and potency of each active
      ingredient. The specificity and stability-indicating characteristics of an assay
      method using high-performance liquid chromatography were validated through forced
      degradation studies. Samples were tested at predefined time intervals over a
      period of 60 days. Preoperative cataract surgery gel maintained the appearance of
      a clear and colorless gel, with pH values ranging form 5.58 to 5.77 throughout
      the study period. The average initial drug concentrations for cyclopentolate
      hydrochloride, phenylephrine hydrochloride, lidocaine hydrochloride, and
      tropicamide were determined to be within +/- 10% of their label concentrations.
      Recovery of the active ingredients at subsequent time points was within +/- 10%
      of their initial concentrations, and chromatographic profile for all tested
      samples exhibited no changes in stability of the active ingredients. The
      ophthalmic gel tested sterile and had no detectable endotoxin during the 60-day
      study period. Preoperative cataract surgery gel packaged in polycarbonate
      syringes and stored protected from light is stable through 60 days at both
      controlled ambient and refrigerated conditions. 

PMID- 23965331
TI  - The release and transdermal penetration of baclofen formulated in a poloxamer
      lecithin organogel.
AB  - The purpose of this study was to evaluate the in vitro release and ex vivo
      penetration of baclofen following incorporation into a 2% poloxamer lecithin
      organogel. Franz cells were utilized for both the release and penetration
      studies. Semi-permeable dialysis membranes were used as the model skin for the
      penetration study. Baclofen release and penetration at predetermined time points
      were assessed using high-performamce liquid chromatographic analysis. Results
      demonstrated that baclofen release from the poloxamer lecithin organogel was
      significantly higher than its penetration through porcine skin. The amount of
      baclofen released by the poloxamer lecithin organogel was linear up to 12 hours.
      Approximately 20% of applied drug was released over the duration of the study
      period. In comparison with drug released, the ex vivo penetration of baclofen
      through porcine skin was very low with only minute detectable quantities
      (significantly less than 1%) after the 12-hour study period. These results
      suggest that the request to include baclofen into a compounded poloxamer lecithin
      organogel should be approached cautiously by compounding pharmacists. 

PMID- 23965332
TI  - Rapid, simple assay for ziprasidone mesylate in extemporaneously compounded oral
      solutions.
AB  - A high-performance liquid chromatographic assay method was developed to
      facilitate stability studies of extemporaneously compounded oral liquid
      formulations of ziprasidone. The method is simple and precise within the needs of
      the pharmaeutical profession. The throughput time is approximately 7 minutes per
      sample. The method is easily adaptable for inidividual needs. 

PMID- 23965333
TI  - First report of anthelmintic resistance in Haemonchus contortus in alpacas in
      Australia.
AB  - BACKGROUND: Parasitic nematodes can cause substantial clinical and subclinical
      problems in alpacas and anthelmintics are regularly used to control parasitic
      nematodes in alpacas. Although anthelmintic resistance has been reported in
      ruminants worldwide, very little is known about anthelmintic resistance in
      alpacas. The present study was carried out to confirm a suspected case of
      anthelmintic resistance in Haemonchus contortus in alpacas in Australia. METHODS:
      Post mortem examination of an alpaca was conducted to determine the cause of its
      death. To confirm a suspected case of macrocyclic lactone (ML) resistance in H.
      contortus in alpacas, a faecal egg count reduction test (FECRT) was performed
      using closantel (7.5 mg/kg) and ivermectin (0.2 mg/kg). Nematode species were
      identified by morphological and molecular methods. RESULTS: Post mortem
      examination of a 1-year-old female alpaca that had died following a brief period
      of lethargy, anorexia and recumbency revealed severe anaemia, hypoproteinaemia
      and gastric parasitism by adult Haemonchus contortus, despite recent abamectin
      (0.2 mg/kg) treatment. Based on these findings and the exclusive use of MLs in
      the herd over the preceding six years, ML resistance in parasitic nematodes of
      alpacas on this farm was suspected. FECRT revealed that the efficacy of closantel
      was 99% (95% CI 93-100), whereas that of ivermectin was 35% (95% CI 0-78),
      indicating that the treatment failure was likely due to the presence of ML
      resistant nematodes. Larval culture of faecal samples collected following
      ivermectin treatment consisted of 99% H. contortus and 1% Cooperia oncophora, a
      result confirmed using a PCR assay. CONCLUSIONS: This study provides the first
      evidence of ML resistance in H. contortus in alpacas in Australia. Based on the
      extent of anthelmintic resistance in sheep gastrointestinal nematodes in
      Australia, veterinarians and alpaca owners should be encouraged to implement
      integrated parasite management strategies to improve nematode control in alpacas.

PMID- 23965334
TI  - Benznidazole treatment of chagasic encephalitis in pregnant woman with AIDS.
AB  - We report a case of chagasic meningoencephalitis reactivation in a pregnant woman
      co-infected with Trypanosoma cruzi and HIV that was successfully managed with
      benznidazole and highly active antiretroviral therapy. Early diagnosis enabled
      rapid specific treatment that improved the health of the patient and her baby. 

PMID- 23965335
TI  - Evaluation of 2 nomogram-based strategies for dosing argatroban in patients with
      known or suspected heparin-induced thrombocytopenia.
AB  - No study has compared 2 different dosing strategies for argatroban titration nor
      has any published nomogram demonstrated improvement in outcomes. This study was
      conducted to evaluate the effectiveness of 2 argatroban nomograms on reaching
      therapeutic anticoagulation. Patients treated with argatroban were separated into
      2 sliding scale groups, percentage adjustments (PAs) and predefined dose
      increments (PDIs). The primary outcome was the time to reach a therapeutic
      activated partial thromboplastin time (aPTT). The average initial dose and dose
      to achieve a therapeutic aPTT were similar between the groups. There was also no
      difference in the number of dose changes. The time to reach a therapeutic aPTT
      was 2 hours shorter in the PDI compared to the PA group, 8 +/- 4 hours versus 10
      +/- 4 hours, P = .015. This study demonstrates a significant time advantage
      associated with a PDI nomogram compared to a PA nomogram but no difference with
      respect to the number of rate changes. 

PMID- 23965336
TI  - Effect of dalteparin on atherosclerotic lesion formation in apolipoprotein E
      deficient mice.
AB  - We aimed to investigate whether prolonged treatment with dalteparin could inhibit
      plaque progression. With C57BL/6J mice as the control, genetically deficient
      apolipoprotein E (apo E) male mice of C57BL/6J strain (apo E(-/-)) were randomly
      divided into 3 groups. The model group received no dalteparin, while the other 2
      groups received dalteparin at 100 and 200 U/kg d, respectively. The aorta was
      harvested for hematoxylin and eosin staining to observe plaque formation and for
      immunohistochemical staining to detect the expression of oxidized low-density
      lipoprotein receptor 1 (LOX-1). The expression of LOX-1 messenger RNA was
      detected by reverse transcription polymerase chain reaction, while the expression
      of LOX-1 protein was detected by Western blotting. Dalteparin decreased aortic
      plaque volume and inhibited aortic LOX-1 protein expression in apo E(-/-) mice.
      The effect persisted 4 weeks after dalteparin treatment was discontinued.
      Dalteparin may inhibit atherosclerotic lesions by downregulating the expression
      of LOX-1 protein. 

PMID- 23965338
TI  - Integration of cardiac proteome biology and medicine by a specialized
      knowledgebase.
AB  - RATIONALE: Omics sciences enable a systems-level perspective in characterizing
      cardiovascular biology. Integration of diverse proteomics data via a
      computational strategy will catalyze the assembly of contextualized knowledge,
      foster discoveries through multidisciplinary investigations, and minimize
      unnecessary redundancy in research efforts. OBJECTIVE: The goal of this project
      is to develop a consolidated cardiac proteome knowledgebase with novel
      bioinformatics pipeline and Web portals, thereby serving as a new resource to
      advance cardiovascular biology and medicine. METHODS AND RESULTS: We created
      Cardiac Organellar Protein Atlas Knowledgebase (COPaKB; www.HeartProteome.org), a
      centralized platform of high-quality cardiac proteomic data, bioinformatics
      tools, and relevant cardiovascular phenotypes. Currently, COPaKB features 8
      organellar modules, comprising 4203 LC-MS/MS experiments from human, mouse,
      drosophila, and Caenorhabditis elegans, as well as expression images of 10,924
      proteins in human myocardium. In addition, the Java-coded bioinformatics tools
      provided by COPaKB enable cardiovascular investigators in all disciplines to
      retrieve and analyze pertinent organellar protein properties of interest.
      CONCLUSIONS: COPaKB provides an innovative and interactive resource that connects
      research interests with the new biological discoveries in protein sciences. With
      an array of intuitive tools in this unified Web server, nonproteomics
      investigators can conveniently collaborate with proteomics specialists to dissect
      the molecular signatures of cardiovascular phenotypes.

PMID- 23965339
TI  - The rationale for intensity-modulated proton therapy in geometrically challenging
      cases.
AB  - Intensity-modulated proton therapy (IMPT) delivered with beam scanning is
      currently available at a limited number of proton centers. However, a simplified
      form of IMPT, the technique of field 'patching', has long been a standard
      practice in proton therapy centers. In field patching, different parts of the
      target volume are treated from different directions, i.e., a part of the tumor
      gets either full dose from a radiation field, or almost no dose. Thus, patching
      represents a form of binary intensity modulation. This study explores the
      limitations of the standard binary field patching technique, and evaluates
      possible dosimetric advantages of continuous dose modulations in IMPT. Specifics
      of the beam delivery technology, i.e., pencil beam scanning versus passive
      scattering and modulation, are not investigated. We have identified two
      geometries of target volumes and organs at risk (OAR) in which the use of field
      patching is severely challenged. We focused our investigations on two patient
      cases that exhibit these geometries: a paraspinal tumor case and a skull-base
      case. For those cases we performed treatment planning comparisons of three
      dimensional conformal proton therapy (3DCPT) with field patching versus IMPT,
      using commercial and in-house software, respectively. We also analyzed the
      robustness of the resulting plans with respect to systematic setup errors of +/-1
      mm and range errors of +/-2.5 mm. IMPT is able to better spare OAR while
      providing superior dose coverage for the challenging cases identified above. Both
      3DCPT and IMPT are sensitive to setup errors and range uncertainties, with IMPT
      showing the largest effect. Nevertheless, when delivery uncertainties are taken
      into account IMPT plans remain superior regarding target coverage and OAR
      sparing. On the other hand, some clinical goals, such as the maximum dose to OAR,
      are more likely to be unmet with IMPT under large range errors. IMPT can
      potentially improve target coverage and OAR sparing in challenging cases, even
      when compared with the relatively complicated and time consuming field patching
      technique. While IMPT plans tend to be more sensitive to delivery uncertainties,
      their dosimetric advantage generally holds. Robust treatment planning techniques
      may further reduce the sensitivity of IMPT plans. 

PMID- 23965340
TI  - Surface roughness induced electron mobility degradation in InAs nanowires.
AB  - In this work, we present a study of the surface roughness dependent electron
      mobility in InAs nanowires grown by the nickel-catalyzed chemical vapor
      deposition method. These nanowires have good crystallinity, well-controlled
      surface morphology without any surface coating or tapering and an excellent peak
      field-effect mobility up to 15,000 cm(2) V(-1) s(-1) when configured into back
      gated field-effect nanowire transistors. Detailed electrical characterizations
      reveal that the electron mobility degrades monotonically with increasing surface
      roughness and diameter scaling, while low-temperature measurements further
      decouple the effects of surface/interface traps and phonon scattering,
      highlighting the dominant impact of surface roughness scattering on the electron
      mobility for miniaturized and surface disordered nanowires. All these factors
      suggest that careful consideration of nanowire geometries and surface condition
      is required for designing devices with optimal performance.

PMID- 23965337
TI  - A receptor-specific function for Notch2 in mediating vascular smooth muscle cell
      growth arrest through cyclin-dependent kinase inhibitor 1B.
AB  - RATIONALE: Deregulated vascular smooth muscle cell (VSMC) proliferation
      contributes to multiple vascular pathologies, and Notch signaling regulates VSMC
      phenotype. OBJECTIVE: Previous work focused on Notch1 and Notch3 in VSMC during
      vascular disease; however, the role of Notch2 is unknown. Because injured murine
      carotid arteries display increased Notch2 in VSMC as compared with uninjured
      arteries, we sought to understand the impact of Notch2 signaling in VSMCs.
      METHODS AND RESULTS: In human primary VSMCs, Jagged-1 (Jag-1) significantly
      reduced proliferation through specific activation of Notch2. Increased levels of
      p27(kip1) were observed downstream of Jag-1/Notch2 signaling and were required
      for cell cycle exit. Jag-1 activation of Notch resulted in increased
      phosphorylation on serine 10, decreased ubiquitination, and prolonged half-life
      of p27(kip1). Jag-1/Notch2 signaling robustly decreased S-phase kinase-associated
      protein, an F-box protein that degrades p27(kip1) during G1. Overexpression of S
      phase kinase-associated protein before Notch activation by Jag-1 suppressed the
      induction of p27(kip1). Additionally, increased Notch2 and p27(kip1) expression
      was colocalized to the nonproliferative zone of injured arteries as indicated by
      co-staining with proliferating cell nuclear antigen, whereas Notch3 was expressed
      throughout normal and injured arteries, suggesting Notch2 may negatively regulate
      lesion formation. CONCLUSIONS: We propose a receptor-specific function for Notch2
      in regulating Jag-1-induced p27(kip1) expression and growth arrest in VSMCs.
      During vascular remodeling, colocalization of Notch2 and p27(kip1) to the
      nonproliferating region supports a model where Notch2 activation may negatively
      regulate VSMC proliferation to lessen the severity of the lesion. Thus, Notch2 is
      a potential target for control of VSMC hyperplasia.

PMID- 23965341
TI  - Spatial control of cell transfection using soluble or solid-phase redox agents
      and a redox-active ferrocenyl lipid.
AB  - We report principles for active, user-defined control over the locations and
      timing with which DNA is expressed in cells. Our approach exploits unique
      properties of a ferrocenyl cationic lipid that is inactive when oxidized, but
      active when chemically reduced. We show that methods that exert spatial control
      over the administration of reducing agents can lead to local activation of
      lipoplexes and spatial control over gene expression. The versatility of this
      approach is demonstrated using both soluble and solid-phase reducing agents.
      These methods provide control over cell transfection, including methods for
      remote activation and the patterning of expression using solid-phase redox
      agents, that are difficult to achieve using conventional lipoplexes. 

PMID- 23965342
TI  - Homeostatic regulation of spontaneous and evoked synaptic transmission in two
      steps.
AB  - BACKGROUND: During development both Hebbian and homeostatic mechanisms regulate
      synaptic efficacy, usually working in opposite directions in response to neuronal
      activity. Homeostatic plasticity has often been investigated by assaying changes
      in spontaneous synaptic transmission resulting from chronic circuit inactivation.
      However, effects of inactivation on evoked transmission have been less frequently
      reported. Importantly, contributions from the effects of circuit inactivation and
      reactivation on synaptic efficacy have not been individuated. RESULTS: Here we
      show for developing hippocampal neurons in primary culture that chronic
      inactivation with TTX results in increased mean amplitude of miniature synaptic
      currents (mEPSCs), but not evoked synaptic currents (eEPSCs). However, changes in
      quantal properties of transmission, partially reflected in mEPSCs, accurately
      predicted higher-order statistical properties of eEPSCs. The classical prediction
      of homeostasis--increased strength of evoked transmission--was realized after
      explicit circuit reactivation, in the form of cells' pairwise connection
      probability. In contrast, distributions of eEPSC amplitudes for control and
      inactivated-then-reactivated groups matched throughout. CONCLUSIONS: Homeostatic
      up-regulation of evoked synaptic transmission in developing hippocampal neurons
      in primary culture requires both the inactivation and reactivation stages,
      leading to a net increase in functional circuit connectivity.

PMID- 23965343
TI  - Computational estimation of tricarboxylic acid cycle fluxes using noisy NMR data
      from cardiac biopsies.
AB  - BACKGROUND: The aerobic energy metabolism of cardiac muscle cells is of major
      importance for the contractile function of the heart. Because energy metabolism
      is very heterogeneously distributed in heart tissue, especially during coronary
      disease, a method to quantify metabolic fluxes in small tissue samples is
      desirable. Taking tissue biopsies after infusion of substrates labeled with
      stable carbon isotopes makes this possible in animal experiments. However, the
      appreciable noise level in NMR spectra of extracted tissue samples makes
      computational estimation of metabolic fluxes challenging and a good method to
      define confidence regions was not yet available. RESULTS: Here we present a
      computational analysis method for nuclear magnetic resonance (NMR) measurements
      of tricarboxylic acid (TCA) cycle metabolites. The method was validated using
      measurements on extracts of single tissue biopsies taken from porcine heart in
      vivo. Isotopic enrichment of glutamate was measured by NMR spectroscopy in tissue
      samples taken at a single time point after the timed infusion of 13C labeled
      substrates for the TCA cycle. The NMR intensities for glutamate were analyzed
      with a computational model describing carbon transitions in the TCA cycle and
      carbon exchange with amino acids. The model dynamics depended on five flux
      parameters, which were optimized to fit the NMR measurements. To determine
      confidence regions for the estimated fluxes, we used the Metropolis-Hastings
      algorithm for Markov chain Monte Carlo (MCMC) sampling to generate extensive
      ensembles of feasible flux combinations that describe the data within measurement
      precision limits. To validate our method, we compared myocardial oxygen
      consumption calculated from the TCA cycle flux with in vivo blood gas
      measurements for 38 hearts under several experimental conditions, e.g. during
      coronary artery narrowing. CONCLUSIONS: Despite the appreciable NMR noise level,
      the oxygen consumption in the tissue samples, estimated from the NMR spectra,
      correlates with blood-gas oxygen uptake measurements for the whole heart. The
      MCMC method provides confidence regions for the estimated metabolic fluxes in
      single cardiac biopsies, taking the quantified measurement noise level and the
      nonlinear dependencies between parameters fully into account.

PMID- 23965344
TI  - TAVI in Europe - that was then and this is now.

PMID- 23965345
TI  - Observations from the CREDO-Kyoto three-vessel disease registry: can one adjust
      for the unadjustable?

PMID- 23965346
TI  - Antithrombotic therapy in PCI: why not heparin?

PMID- 23965347
TI  - More than ever, a true need to work together: Stent for Life.

PMID- 23965349
TI  - Outcome of patients after emergency conversion from transcatheter aortic valve
      implantation to surgery.
AB  - AIMS: To evaluate: 1) the causes of emergency conversion from transcatheter
      aortic valve implantation (TAVI) to surgery, 2) procedural settings, and 3) short
      term outcome of converted patients. METHODS AND RESULTS: The prospective German
      TAVI registry was used to identify patients who underwent bail-out surgery during
      TAVI. Additionally, standardised questionnaires were developed and used to assess
      more detailed periprocedural and postprocedural data. Emergency conversion from
      TAVI to open cardiac surgery was required in 24 of 1,975 patients (1.2%). Primary
      conversion causes were aorto-valvular complications (i.e., aortic annulus
      rupture, aortic perforation, or thoracic aortic dissection). This was followed by
      prosthesis embolisation, myocardial perforation, severe aortic regurgitation, and
      coronary obstructions. The mean time interval between abortions of TAVI to
      surgery was 19 minutes (SD +/- 17 min, range 5-80 min). Four of 24 patients
      (16.7%) died during the initial surgery, seven of 24 (29.2%) within the first 72
      hours and the 30-day mortality was 45.8%. The highest mortality was observed in
      patients with aortic perforation or dissection (4/5, 80%). Mortality rates for
      other entities were: prosthesis embolisation 40% (2/5), myocardial perforation
      50% (2/4), annulus rupture 67% (2/3), severe aortic regurgitation 33% (1/3), and
      coronary impairment 0% (0/3). CONCLUSIONS: Emergency conversion from TAVI to
      surgery is a rare event carrying a mortality of around 45% after 30 days. Outcome
      of converted patients with prior injury of aortic, aorto-valvular, or myocardial
      tissue during TAVI was poor, whereas patients with severe aortic regurgitation
      and those with coronary complications had a more favourable outcome after 30
      days. Collected procedural and outcome data demand on-site cardiac surgery as a
      prerequisite for TAVI and constant process optimisation efforts regarding such
      emergency scenarios.

PMID- 23965350
TI  - Two-year outcomes of everolimus vs. paclitaxel-eluting stent for the treatment of
      unprotected left main lesions: a propensity score matching comparison of patients
      included in the French Left Main Taxus (FLM Taxus) and the LEft MAin Xience
      (LEMAX) registries.
AB  - AIMS: With newer drug-eluting stents (DES), PCI has appeared as an acceptable
      alternative to cardiac surgery in the treatment of unprotected left main (ULM)
      lesions. Using data from the French Left Main Taxus and the LEft MAin Xience
      registries, we compared two-year outcomes in consecutive patients from 2003-2008
      using everolimus-eluting stents (EES) vs. paclitaxel-eluting stents (PES).
      METHODS AND RESULTS: We performed a matched comparison according to SYNTAX score,
      distal LM stenosis, provisional side-branch T-stenting and single stent use,
      focusing on the primary endpoints of target vessel MI (TVMI) and target vessel
      failure (TVF). After propensity score matching, there were 172 patients in each
      group. There was no difference in gender (76.5% male), age (69.5 +/- 11.3 years),
      diabetes (26.2% vs. 24.4%, p=0.71), NSTEMI (40.7% vs. 40.7%, p=1), or LVEF <40%
      (11.0% vs. 6.7%, p=0.22). Patients with distal LM lesions (75.9%) were treated
      using provisional T-stenting in 91.1%. The side branch was stented in 22% of all
      patients (p=0.51). Cumulative two-year events showed significant differences in
      TVMI (9.9% vs. 4.1%, p=0.04) and TVF (16.3% vs. 7.6%, p=0.01) for PES and EES,
      respectively. CONCLUSIONS: ULM stenting with EES is safer and more effective than
      PES with a reduction in TLF by 53% at two years.

PMID- 23965351
TI  - New technical and anticoagulation aspects for left atrial appendage closure using
      the WATCHMAN(r) device in patients not taking warfarin.
AB  - AIMS: The WATCHMAN(r) device was proven non-inferior to oral anticoagulation
      (OAT). However, periprocedural risks and uncertainty regarding patients with
      absolute contraindication for OAT limit the overall utilisation of this approach.
      We investigated the periprocedural safety of dual platelet inhibition and primary
      utilisation of larger device diameters in order to minimise peri-device leakage
      and repositioning of the device during the implantation process. METHODS AND
      RESULTS: Since 2010, 59 consecutive patients have been treated with the
      WATCHMAN(r) device and followed for six months. In patients with
      contraindications to warfarin, dual antiplatelet therapy (DAPT) was used during
      the first 45 days after implantation instead of warfarin. Device size was chosen
      15-30% greater than the LAA diameter in order to minimise device repositioning
      and leakage, and to prevent device embolisation. Small, non-trabecular recesses
      at the superior ridge towards the inferior, left pulmonary vein were regularly
      observed and followed by transoesophageal echo regarding thrombus formation. We
      observed a 3.3% rate of pericardial effusions and a 5% rate of thrombi at the
      device during the healing period of 45 days and no device embolisations. One
      thromboembolic event without clinical sequelae was observed during the six-month
      follow-up period. All patients stopped DAPT at six months as no primary or
      secondary leakage >5 mm around the device perimeter was observed. CONCLUSIONS:
      Our data suggest that DAPT can be used safely during the first 45 days in
      patients with contraindications to warfarin. An algorithm employing larger
      devices in relation to the LAA ostium with consecutively larger compression
      improved procedural safety compared to the current standard regarding leakage and
      device repositioning.

PMID- 23965348
TI  - Three-year outcome after percutaneous coronary intervention and coronary artery
      bypass grafting in patients with triple-vessel coronary artery disease:
      observations from the CREDO-Kyoto PCI/CABG registry cohort-2.
AB  - AIMS: We sought to investigate medium-term outcome of percutaneous coronary
      intervention (PCI) compared with coronary artery bypass grafting (CABG) in
      patients with triple-vessel coronary artery disease (TVD). METHODS AND RESULTS:
      We identified 2,981 patients with TVD (PCI: N=1,825, CABG: N=1,156) among 15,939
      patients with first coronary revascularisation enrolled in the CREDO-Kyoto
      PCI/CABG registry cohort-2. Excess adjusted three-year risk of the PCI group
      relative to the CABG group for death/myocardial infarction (MI)/stroke was
      significant (HR 1.47 [95% CI: 1.13-1.92, p=0.004]). Adjusted risk for all-cause
      death was also significantly higher with PCI as compared with CABG (HR 1.62 [95%
      CI: 1.16-2.27, p=0.005]), while risk for cardiac death was neutral between the
      two groups (HR 1.3 [95% CI: 0.81-2.07, p=0.28]). PCI was also associated with a
      markedly higher risk for any coronary revascularisation. Regarding the analysis
      stratified by the SYNTAX score, the adjusted HR of PCI relative to CABG for
      death/MI/stroke was 1.66 (95% CI: 1.04-2.65, p=0.03) in the low-score (<23:
      N=874, and N=257), 1.24 (95% CI: 0.83-1.85, p=0.29) in the intermediate-score (23
      32: N=638, and N=388), and 1.59 (95% CI: 0.998-2.54, p=0.051) in the high-score
      (>= 33: N=280, and N=375) tertiles, respectively. CONCLUSIONS: PCI as compared
      with CABG was associated with significantly higher risk for serious adverse
      events in TVD patients.

PMID- 23965352
TI  - Persistent geographical disparities in the use of primary percutaneous coronary
      intervention in 120 European regions: exploring the variation.
AB  - AIMS: Large inequalities in the use of primary percutaneous interventions (PPCI)
      for ST-elevation myocardial infarction (STEMI) are evident. In order to
      understand how we can help to implement best practice for STEMI patients, we
      investigated the variation in PPCI utilisation in 120 regions in 10 EU countries
      and the association with economic, organisational and demographic
      characteristics. METHODS AND RESULTS: We performed an ecological study using
      mixed effects regression models in the following 10 countries: Austria, Belgium,
      Denmark, England and Wales, Germany, Italy, Portugal, Spain, Sweden, and Northern
      Ireland. The main finding was the annual number of PPCI per million inhabitants
      from 2003 through 2008. Overall, the annual increase in PPCI utilisation was 1.15
      (95% CI: 1.12, 1.19) per million per year. Regional-level rates varied from 0.74
      (95% CI: 0.42, 1.30) to 1.90 (95 % CI: 1.01, 3.55) per million per year. At a
      regional level, significant positive associations with PPCI utilisation were the
      number of physicians per 100,000 inhabitants; the number of nurses and midwives
      per 100,000 inhabitants; and the proportion of the region's population aged 50 to
      <70 years. At a country level, significant positive associations with utilisation
      were the year of STEMI treatment, population density per km2; number of general
      hospital beds per 100,000 inhabitants; and the number of physicians per 100,000
      inhabitants. CONCLUSIONS: Between 2003 and 2008, PPCI utilisation increased
      significantly in the ten European countries studied, but there was a great
      variation within country regions. Regional variation in PPCI rates were
      associated with both demographic and supply factors, revealing substantial
      opportunities to improve PPCI utilisation across Europe at national and regional
      levels.

PMID- 23965353
TI  - Implementation of a physician-staffed helicopter: impact on time to primary PCI.
AB  - AIMS: This study aimed to compare air (AIR) and ground transport (GRD) of STEMI
      patients bound for primary percutaneous coronary intervention (pPCI). METHODS AND
      RESULTS: This was a prospective, controlled, observational study, including
      patients in whom STEMI was suspected outside a 30-minute driving distance from
      the PCI centre. AIR patients in a 12-month period (May 1, 2010, to April 30,
      2011) were compared with GRD patients in a 16-month period (January 1, 2010, to
      April 30, 2011). The primary endpoint was time from ECG consistent with STEMI to
      arrival in the cardiac catheterisation laboratory. We included 450 patients, 114
      AIR and 336 GRD patients. The median (5-95% range) transport distance was 97 (62
      162) vs. 94 (64-172) kilometres, respectively (p=0.01). Time from ECG to cardiac
      catheterisation laboratory arrival was significantly lower in the AIR group
      (median 84 minutes (60-160) vs.104 minutes [63-225], p<0.01). Time from ECG to
      balloon was 114 (78-221) minutes vs.132 (84-262) (p<0.01), respectively. The 30
      day mortality was 2.2% (2/91) for AIR and 6.9% (18/262) for GRD patients
      (p=0.10). One-year mortality was 6.7%, (6/90) vs. 9.9% (26/262) (p=0.35),
      respectively. CONCLUSIONS: Air transport seemed superior to ground transportation
      in reducing time from ECG diagnosis to arrival in the catheterisation laboratory
      for STEMI patients outside a 30-minute driving distance to the PCI centre.

PMID- 23965355
TI  - First-in-human evaluation of the novel BioMime sirolimus-eluting coronary stent
      with bioabsorbable polymer for the treatment of single de novo lesions located in
      native coronary vessels - results from the meriT-1 trial.
AB  - AIMS: We report the initial human evaluation of the novel BioMimeTM sirolimus
      eluting stent (SES) (Meril Life Sciences Pvt. Ltd., Gujarat, India) with an ultra
      thin stent platform (65 MUm) and a biodegradable polymer for the treatment of de
      novo coronary lesions. METHODS AND RESULTS: The meriT-1 trial was a prospective,
      non-randomised, single-arm, single-centre, first-in-human evaluation of the
      safety, feasibility and performance of the BioMime SES. Lesion criteria included
      non-occlusive stenosis <= 19 mm in length located in native coronary vessels.
      Clinical follow-up (FU) was performed at 1, 8 and 12 months; all patients were
      assigned for angiographic FU at eight months. A total of 30 patients (30 lesions)
      were enrolled between March 2009 and February 2010. Mean age was 49.9 years, 30%
      were diabetics, and 36.7% had previous myocardial infarction (MI). Baseline
      median [25%, 75% interquartile range] lesion length, reference diameter and %
      diameter stenosis were 15.51 mm [12.74, 20.27], 2.94 mm [2.71, 3.34], and 80.5%
      [67.0%, 90.7%], respectively. Overall, there was one stent implanted per lesion
      and procedural success was 100%. At eight-month angiographic FU (26/30), median
      in-stent late lumen loss was 0.15 mm [0.09, 0.33]; also, there were no cases of
      binary restenosis within the treated segment. Clinical FU at 12 months (100%)
      demonstrated absence of MACE (cardiac death, MI and target lesion
      revascularisation) and stent thrombosis (ST). CONCLUSIONS: The novel BioMime SES
      demonstrated excellent performance in single coronary lesions including high
      procedural success and efficacy, as demonstrated by the relatively low late lumen
      loss (a surrogate of neointimal hyperplasia) at eight-month angiographic FU.
      Overall, there were no safety concerns in this preliminary evaluation including
      absence of MACE or ST up to 12 months.

PMID- 23965354
TI  - Rationale and design of a large registry on renal denervation: the Global
      SYMPLICITY registry.
AB  - AIMS: Hypertension is a global healthcare concern associated with a wide range of
      comorbidities. The recognition that elevated sympathetic drive plays an important
      role in the pathogenesis of hypertension led to the use of renal artery
      denervation to interrupt the efferent and afferent sympathetic nerves between the
      brain and kidneys to lower blood pressure. Clinical trials of the SymplicityTM
      renal denervation system have demonstrated that radiofrequency ablation of renal
      artery nerves is safe and significantly lowers blood pressure in patients with
      severe resistant (systolic BP >160 mmHg) hypertension. Smaller ancillary studies
      in hypertensive patients suggest a benefit from renal denervation in a variety of
      conditions such as chronic kidney disease, glucose intolerance, sleep apnoea and
      heart failure. METHODS AND RESULTS: The Global SYMPLICITY registry, which
      incorporates the GREAT SYMPLICITY registry initiated in Germany, is being
      conducted worldwide to evaluate the safety and efficacy of treatment with the
      Symplicity renal denervation system in real-world uncontrolled hypertensive
      patients, looking first at subjects with severe resistant hypertension to confirm
      the results of prior clinical trials, but then also subjects with a wider range
      of baseline blood pressure and coexisting comorbidities. CONCLUSIONS: The
      rationale, design and first baseline data from the Global SYMPLICITY registry are
      presented.

PMID- 23965356
TI  - Stent healing response following delivery of paclitaxel via durable polymeric
      matrix versus iopromide-based balloon coating in the familial
      hypercholesterolaemic swine model of coronary injury.
AB  - AIMS: The routine use of paclitaxel-coated balloons (PCB) in combination with
      bare metal stents (BMS) in de novo coronary lesions has been questioned. In this
      study, we aimed to compare the vascular response of BMS implanted using a second
      generation PCB (BMS+PCB) with the TAXUS stent (PES) and a BMS control (BMS) in
      the familial hypercholesterolaemic swine (FHS) model of coronary injury. METHODS
      AND RESULTS: A total of 17 stents (PES=6, BMS+PCB=6, and BMS=5) were implanted in
      the coronary territory of 10 FHS using a 20% overstretch injury ratio. Imaging
      evaluation (QCA and IVUS) was conducted in all animals at baseline and 28 days
      following stent implantation. Following terminal imaging all animals were
      euthanised and stented coronary segments harvested for histological evaluation.
      At 28 days, the lowest degree of percentage diameter stenosis by QCA was achieved
      by the PES (2.9 +/- 9%) followed by the BMS+PCB (9.5 +/- 16.4%) and the BMS group
      (25.65 +/- 18.7%, p<0.05). In histology, percentage area of stenosis
      (BMS+PCB=29.6 +/- 6.4% vs. PES=21.5 +/- 3.3% vs. BMS=55.2 +/- 12.9%; p<0.01) and
      neointimal thickness (BMS+PCB=0.26 +/- 0.1 mm vs. PES=0.21 +/- 0.1 mm vs.
      BMS=0.59 +/- 0.2 mm; p<0.01) were significantly reduced in both paclitaxel groups
      in comparison to BMS controls. Both BMS+PCB and BMS groups had higher
      endothelialisation scores (PES=1.50 +/- 0.9 vs. BMS+PCB=2.73 +/- 0.4 vs.
      BMS=3.00; p<0.05) and lower peri-strut inflammatory scores (PES=0.83 +/- 0.4 vs.
      BMS+PCB=0.20 +/- 0.2 vs. BMS=0.43 +/- 0.6, p<0.05) when compared to PES.
      Neointima maturity (PCB+BMS: 2.00 [2-2.4] vs. PES: 1.00 [0.3-1] vs. BMS: 3.00,
      p<0.05) and fibrin deposition (PCB+BMS: 1.40 +/- 0.3 vs. PES: 2.17 +/- 0.7 vs.
      BMS: 0.27 +/- 0.3, p<0.05) scores in PCB+BMS appeared to fall between the PES and
      the BMS ranges. CONCLUSIONS: In the FHS coronary injury model, BMS implantation
      using a PCB yields a degree of neointimal inhibition comparable to the PES. The
      BMS+PCB combination presented lower degrees of inflammation and fibrin
      deposition; however, signs of delayed healing were still present.

PMID- 23965357
TI  - The role of the emergency services in the optimisation of primary angioplasty:
      experience from London and the Heart Attack Team.
AB  - Early ambulance services often confined their activities to a "scoop and run"
      approach, conveying sick patients quickly to the nearest emergency department.
      With the advent of modern ST-elevation myocardial infarction (STEMI) management
      and primary percutaneous coronary intervention (PPCI), the role of the emergency
      medical service (EMS) has expanded significantly. This review discusses the
      critical and evolving collaboration between the EMS and the heart attack centre.
      Speed of reperfusion is a major determinant of outcome in STEMI and, whilst the
      patient delay (symptom to call time) has a central role in this, system delay
      (first medical contact to balloon time) is linked to mortality and is used to
      measure the response of a PPCI programme and is a key element of contemporary
      guidelines. In addition to rapid diagnosis and transfer to the heart attack
      centre, the EMS has to deliver a growing number of established treatments
      including resuscitation and drug therapy. EMS also continually needs to develop
      expertise in new techniques such as advanced management of cardiac arrest
      patients, including automated cardiopulmonary resuscitation, and will need to
      deliver newer therapies if trials support their use, including cooling and
      preconditioning. Ultimately, the EMS has a central role in the management of
      STEMI patients which needs to be fully aligned with the heart attack centres.
      This integration of services is perhaps best regarded as the Heart Attack Team. 

PMID- 23965358
TI  - Tools and Techniques Clinical: transcatheter closure of left atrial appendage
      using the AmplatzerTM Cardiac Plug.

PMID- 23965359
TI  - How should I treat stent dislodgement in a STEMI patient resulting in dissection
      of left main and left circumflex arteries?
AB  - BACKGROUND: A 52-year-old female presented with acute anterior ST-elevation
      myocardial infarction (STEMI) within one hour of symptom onset to the emergency
      department. She was referred for urgent primary angioplasty. INVESTIGATION:
      Physical examination, laboratory investigations, ECG, urgent percutaneous
      coronary intervention (PCI). DIAGNOSIS: Single-vessel coronary artery disease
      (SVD). TREATMENT: Intended to stent culprit lesion. However, stent dislodged in
      left main coronary artery (LMCA) during attempted PCI to diffuse mid segment of
      left anterior descending (LAD). Initial attempt failed to retrieve the dislodged
      stent with snare. Dislodged stent removed with multiple wire technique,
      complicated by severe dissection in LAD and left circumflex artery back into the
      LMCA. The stent was trapped at tip of 6 Fr right femoral sheath, unable to be
      withdrawn. What next?

PMID- 23965361
TI  - Prescription.

PMID- 23965360
TI  - Rosiglitazone attenuates casein-induced hepatic endoplasmic reticulum stress in
      Sprague-Dawley rats: a novel model of endoplasmic reticulum stress.
AB  - The proteins found in cow milk have been reported to cause systemic inflammation.
      Endoplasmic reticulum (ER) stress is known to be involved in the development of
      several metabolic disorders including insulin resistance and non-alcoholic fatty
      liver disease. However, the effect of thiazolidinediones (TZDs) on ER stress is
      still controversial. This is why we want to investigate in this study whether
      casein, which is the major protein in cow's milk, induces ER stress in the liver
      and whether rosiglitazone can attenuate these changes. Nine-week-old male Sprague
      Dawley (SD) rats were separated into three groups: (1) vehicle treated; (2) daily
      subcutaneous injections of 1 mL 10% casein; (3) daily subcutaneous injection of 1
      mL 10% casein and rosiglitazone 4 mg/[kg d]. After 6 weeks, body weight, food
      intake, glucose and lipid parameters, and serum AST/ALT levels were measured
      after an overnight fast. Real time RT-PCR and immunohistochemical staining for
      various ER stress markers were performed, and a TUNEL analysis was also
      performed. After 6 weeks, casein injection induced weight reduction, systemic
      inflammation, and hepatic dysfunction in SD rats. Casein injection increased both
      the gene and protein expression of ER stress markers in the liver and also caused
      hepatocyte apoptosis. Rosiglitazone treatment attenuated casein-induced systemic
      inflammation, ER stress, deteriorated liver function, and increased apoptosis. In
      conclusion, our results may provide further insight into the effects of casein on
      chronic inflammatory diseases, and to have a better understanding of the
      mechanism of the anti-inflammatory properties of rosiglitazone regardless of its
      hypoglycemic effect.

PMID- 23965362
TI  - When traditional medicine fails.
AB  - The focus of most medical schools, residencies, and ongoing post-graduate
      training is on treatable conditions. Unfortunately, today's society and medical
      systems are ill-equipped to meet the needs of children who have been diagnosed
      with a terminal illness. This article discusses suggested steps to assist
      terminally ill children in successfully concluding their lives. It emphasizes the
      importance of a team of healthcare professionals to provide comprehensive and
      integrated care for the child and the child's family. Because of their small size
      and the high tendency of adverse reactions to manufactured one-size-fits-all
      drugs, pediatric patients are a unique and specialized group requiring unique and
      specialized medications. These medications can be prepared by compounding
      pharmacists, integral participants of the healthcare team. 

PMID- 23965363
TI  - Sleepless in america: compounding with melatonin.
AB  - Studies of Melatonin in the 1970s and 1980s revealed sedative and hypnotic
      properties of the compound, which have led to its use in treating sleep
      disorders. Commonly used for jet lag, melatonin is relatively inexpensive and
      associated with minimal side effects. Regulation of melatonin secretion appears
      to be abnormal in children and adults in which pervasive development disorders
      have been observed. Alteration in melatonin rhythm may be responsible for sleep
      onset and maintenance difficulties in autism. A recent review concluded that
      melatonin primarily acts on the total length of time needed to fall asleep and on
      the total length of sleep. In addition, melatonin, which does not induce
      dependence or withdrawal syndromes, may have advantages compared to commonly
      prescribed benzodiazepines. While there is an enormous amount of anecdotal
      information available, additional studies are necessary involving melatonin for
      the treatment of sleep disorders. The condition of these well-controlled studies
      must be clearly defined, especially in regards to the melatonin formulation and
      pharmacology of the products used. Various areas remain unclear, such as how the
      effects of melatonin vary by age, gender, ethnicity, and comorbid conditions of
      the population, as well as formulation, timing, and duration of melatonin
      administration. While the U.S. Food and Drug Administration does not strictly
      regulate herbs and supplements, based on available studies and clinical use,
      melatonin is generally regarded as safe in recommended doses when used in the
      short term. The safety of melatonin when used in the long term remains unclear. 

PMID- 23965364
TI  - Prophylaxis against exposure to bloodborne pathogens during compounding.
AB  - Unintentional exposure to biologic pathogens can occur when preparations that
      contain blood or its components are compounded. For example, autologous eye
      drops, which are not commercially manufactured, incorporate serum that must be
      handled by various staff members in a compounding pharmacy. In this report, we
      describe workplace practices and materials used to inform our staff members who
      handle or compound that preparation and other similar formulations about the safe
      and appropriate handling of blood or body fluids that could contain biologic
      pathogens. Compounding pharmacists who must develop and implement a standard
      operating procedure for managing exposures to bloodborne pathogens will find the
      prototype plan presented in this article of interest. 

PMID- 23965365
TI  - Compounding pharmacy: a unique service for a unique population.
AB  - Abstract not available. 

PMID- 23965366
TI  - Calculating carbohydrate content of compounded medications for patients on a
      ketogenic diet.
AB  - The ketogenic diet is a high-fat, low carbohydrate, and low-protein diet designed
      to increase the body's dependence on fatty acids for energy rather than glucose.
      This diet is used as a treatment option for young children with refractory
      seizure disorders or inborn metabolic defects. Children on this diet must be
      closely monitored by a team of healthcare professionals consisting of
      neurologists. Accurate Calculations for daily allowances of carbohydrates, fats,
      and proteins are essential for success of the treatment. Since pediatric patients
      that are on the ketogenic diet often take compounded medications, there is also a
      need to determine the carbohydrate content of the compounded medications.
      Researching and trying to calculate the carbohydrate content of compounded
      medications can be very time consuming. A group of PharmD candidates from Purdue
      University were provided with copies of the top 100 compounded oral liquids
      prepared at Clarian Health Partners, Inc. Their extensive research resulted in a
      comprehensive, quick reference list of common compounded medications and their
      respective carbohydrate content, the list of which is provided in this article.
      This list can aid physicians, caregivers, dieticians, and pharmacists in quickly
      calculating the patient's daily carbohydrate allowance, allowing more time to be
      devoted to other patient care needs. 

PMID- 23965367
TI  - Providing consultation services for wellness issues related to excercise, weight
      management, and nutritional support: key lifestyle modifications for healthier
      aging.
AB  - This article discusses the importance of compounding pharmacies offering
      consultation services to patients, specifically in the areas of exercise, weight
      management, and nutritional support. With approximately two-thirds of the adult
      U.S. population falling into the overweight category and almost one-third falling
      into the obese category, most of which are also underactive, clearly weight
      management is an area of great concern. Included in this article are some brief
      literature reviews; important information for those looking for statistics on the
      benefits of exercise and nutritional support. Vitamin D and Omega 3 fatty acid
      research information is provided, highlighting the broad-based benefits of these
      important supplements. Having a private, inviting space for your patients to
      discuss their concerns and prescription needs, encourages patients to use
      consulting services and having fact-based information can help educate your
      patients about the topics discussed in this article, as well as other healthcare
      needs. 

PMID- 23965368
TI  - Unit-dose packaging and repackaging of solid and liquid dosage forms in an
      institutional setting.
AB  - Although repackaging drugs into unit-dose packages can be time consuming and
      labor intensive, it can significantly reduce medication errors and improve
      patient safety in health systems. Pharmacists can play a vital role in choosing
      appropriate repackaging equipment and labeling programs that are compatible with
      the health system's Bar-Code-Enabled Medication Administration system. They can
      develop policies and procedures for repackaging drugs and ensuring that all
      medications have scan-able barcodes or identifiers. Pharmacists can also develop
      a quality-assurance program to ensure that the Bar-Code-Enabled Medication
      Administration system is effective and that the unit-dose packaging operations
      meet United States Pharmacopeial Convention standards and other professional
      guidelines. 

PMID- 23965369
TI  - Diverse challenges in pediatric compounding: treating pulmonary hypertension,
      uncombable hair syndrome, and acanthamoeba keratitis.
AB  - The market for commercially manufactured drugs for pediatric patients is smaller
      than that for adults, and most of the medications currently used to treat
      children, including many over-the-counter products, have not been clinically
      studied in the pediatric population. Thus a customized medication that is
      formulated to meet the unique needs of the pediatric patient and that can be
      quickly adjusted to more effectively address a child's changing medical needs can
      be essential to a successful therapeutic outcome. Compounding pharmacists are
      often faced with the demand for a novel pediatric preparation that overcomes the
      patient's taste aversions or resistance to a particular dosage form, and
      successful treatment can depend on the compounder's problem-solving skills and
      therapeutic innovation. In this article, we describe the effective treatment of
      three children whose medical needs were unmet by manufactured medications. The
      formulations for the preparations used are also provided. 

PMID- 23965371
TI  - Literature review and importance of quality control.

PMID- 23965370
TI  - An academic-practice partnership: an innovative course in advanced compounding.
AB  - Over the past century, as the dynamic of pharmacy practice has evolved, there has
      been continual ebb and flow in the practice of compounding. However, the basic
      art and science remain the same. Mirroring these practice trends, education in
      the components of compounding and curricular requirements in many Doctor of
      Pharmacy programs has also experienced many changes. At the University Of
      Washington School Of Pharmacy, students receive basic instruction in the science
      and techniques of compounding during their first professional year, but little
      further. To accommodate an increasing interest in the art, science, and practice
      of compounding in community pharmacy, the University Of Washington School Of
      Pharmacy created a unique elective in advanced compounding skills. This intensive
      course operates over a weekend at a successful community compounding pharmacy
      located in central Washington State. The course is primarily taught by the
      pharmacy owner and other pharmacists with compounding expertise. This article
      describes the evolution, assessment, and future potential of this advanced
      compounding elective at the University Of Washington School Of Pharmacy. 

PMID- 23965372
TI  - Considerations for implementing United States pharmacopeia chapter 797
      pharmaceutical compounding-sterile preparations.
AB  - To ensure the quality of compounded preparations, an efficient quality-assurance
      program is necessary. This article clearly defines the elements necessary to
      establish a quality-assurance program that meets the standards set forth in the
      United States Pharmacopeia in the area of personnel training. It is essential
      that compounders have knowledge of the substances used in compounding and the
      devices used in the compounding facility. Specific and continuous training is
      essential to provide the compounder with the necessary knowledge to get the job
      completed. Knowledge of basic science principles is necessary to enable the
      compounder to understand and interpret scientific data and reports provided by
      the suppliers. In addition, handling and manipulating the equipment requires
      specific training to ensure that the results generated by the equipment are
      correct and accurate. 

PMID- 23965373
TI  - Chemical stability of hydrocortisone in humco simple syrup and ora-sweet
      vehicles.
AB  - The chemical stability of hydrocortisone in two different commercially available
      vehicles for compounding oral liquid dosage forms has been studies using a
      stability-indicating high-performance liquid chromatographic assay method that
      was developed in our laboratory. Hydrocortisone was more stable in Ora-Sweet
      vehicle than in Humco simple syrup. After 71 days of storage at 60 degrees
      Celsius, the percent of hydrocortisone retained in Humco simple syrup was 62.8 (
      initial pH value of the dosage form was 5.2) versus 67.7 in Ora-Sweet vehicle
      (initial pH value of the dosage form was 4.3). Due to the hydrolysis of sugar,
      the physical appearances of both the dosage forms gradually changed from almost
      colorless to yellow. Citric acid, which was present only in the Ora-Sweet
      vehicle, did not adversely affect the stability of hydrocortisone. 

PMID- 23965374
TI  - Evaluation of a simple method for visual detection of microprecipitates in blends
      of parenteral drug solutions using a focused (tyndall) light beam.
AB  - The formation of microprecipitates (sub visible particles) is a critical factor
      when blending parenteral drug solutions prior to or during intravenous
      administration to a patient. In cases where compatibility is not documented,
      analytical screening of such mixtures for physical incompatibility would give a
      safer foundation for secure administration of such blends to patients. The aim of
      this article is to report our experiences with visual screening using a focused
      (Tyndall) light beam for the detection of micro precipitates within blends of
      drug solutions, a method which may be used in any hospital pharmacy without use
      of advanced analytical instrumentation. A selection of clinically applied drug
      solutions was tested for precipitation upon blending in a proportion of 1:1. In
      order to reduce potential background particle burden, the solutions were filtered
      through 0.2 micrometer pore size filters prior to mixing. To detect potential
      precipitation, the solutions were visually inspected using two different types of
      focused light beams, a 75-watt white, focused light source and a HeNe pocket
      laser-pointer, for light scattering. For comparison, a light obscuration particle
      counter test was performed as described in the European Pharmacopeia. An
      experimental set-up is described, and a detailed protocol is suggested for a
      method able to detect micro precipitates in drug solution blends by using focused
      (Tyndall) light. The performance of this method for selected blends is reported
      in comparison to the Pharmacopeial light obscuration particle count test. Despite
      the fact that visual inspection using Tyndall light is a simple and low-cost
      method, it was found sensitive for detecting minute amounts of sub visible
      particles with detection sensitivity close to the light obscuration particle
      counting limits stated by the European Pharmacopeia. In cases where an electronic
      particle counter is not accessible, a sensitive warning signal may be obtained
      from this approach indicating that it is not advisable to mix such solutions.
      Certain drug solutions, as well as their actual concentrations, can have an
      effect on precipitation, and, therefore, should be recorded in mixing tables for
      clinical use. The Tyndall method employed here may represent an important tool
      for improving the quality of decisions on whether to give two solutions
      simultaneously to a patient. 

PMID- 23965375
TI  - Stability of Oseltamivir Phosphate in SyrSpend SF, Cherry Syrup, and SyrSpend SF
      (For Reconstitution).
AB  - Oseltamivir (Tamiflu) is widely prescribed to treat and prevent influenza virus
      A, influenza virus B, and H1N1 Flu. It is manufactured by Roche in 75-mg
      capsules. The need for other administration options for patients who cannot take
      capsules and cannot use suspending agents which contain alcohol, sorbitol, or
      preservatives has led to the compounding of oseltamivir into three suspending
      vehicles that do not contain these chemicals. All three contain neither alcohol
      nor sorbitol; the third also has no preservatives, a distinct advantage for
      special patient situations. The objective of this study was to determine the
      stability of oseltamivir in three different suspending agents: SyrSpend SF,
      Cherry Syrup, and SyrSpend SF (for reconstitution). The studied samples were
      compounded into 15-mg/mL suspensions and stored in low actinic plastic
      prescription bottles at temperatures between 2 degrees Celsius and 8 degrees
      Celsius. Triplicate samples were assayed at time intervals out to 30 days by a
      stability-indicating high-performance liquid chromatography method. The method
      was validated for its specificity through forced degradation studies. All of the
      samples tested remained within 90% to 110% of their initial concentrations
      throughout the course of the study. The shelf life of these products is at least
      30 days, based on data collected when the aforementioned products are
      refrigerated and protected from light. Based on the final potency data at day 30,
      the shelf life may extend past the scope of this study, but 30 days was the limit
      of this study. 

PMID- 23965376
TI  - Meditation increases compassionate responses to suffering.

PMID- 23965377
TI  - Women's luteal-phase sexual proceptivity and the functions of extended sexuality.
AB  - Women's sexuality, unlike that of most mammals, is not solely defined by sexual
      receptivity during the short window of fertility. Women demonstrate extended
      sexuality (in which they initiate and accept sexual advances outside of the
      fertile phase) more than any other mammalian female. In this light, surprisingly
      little research has addressed the functions of women's luteal-phase sexuality. On
      the basis of theory and comparative evidence, we propose that women's initiation
      of sex during nonfertile phases evolved in part to garner investment from male
      partners. If so, women should be particularly prone to initiate luteal-phase sex
      when the potential marginal gains are greatest. Results from a study of 50
      heterosexual couples showed that women increasingly initiate sex in the luteal
      phase (but not the fertile phase) when they perceive their partners' investment
      to lag behind their own. These findings provide evidence for the distinct nature
      of women's extended sexuality and may contribute to a more comprehensive
      understanding of women's sexuality. 

PMID- 23965378
TI  - Spread of Neisseria meningitidis serogroup W clone, China.
AB  - During February 2011-June 2012, invasive infection with Neisseria meningitidis
      serogroup W was identified in 11 persons in southeastern China. All isolates
      tested had matching or near-matching pulsed-field gel electrophoresis patterns
      and belonged to multilocus sequence type 11. The epidemiologic investigation
      suggested recent transmission of this clonal complex in southeastern China. 

PMID- 23965379
TI  - Adaptive evolution of tight junction protein claudin-14 in echolocating whales.
AB  - Toothed whales and bats have independently evolved specialized ultrasonic hearing
      for echolocation. Recent findings have suggested that several genes including
      Prestin, Tmc1, Pjvk and KCNQ4 appear to have undergone molecular adaptations
      associated with the evolution of this ultrasonic hearing in mammals. Here we
      studied the hearing gene Cldn14, which encodes the claudin-14 protein and is a
      member of tight junction proteins that functions in the organ of Corti in the
      inner ear to maintain a cationic gradient between endolymph and perilymph.
      Particular mutations in human claudin-14 give rise to non-syndromic deafness,
      suggesting an essential role in hearing. Our results uncovered two bursts of
      positive selection, one in the ancestral branch of all toothed whales and a
      second in the branch leading to the delphinid, phocoenid and ziphiid whales.
      These two branches are the same as those previously reported to show positive
      selection in the Prestin gene. Furthermore, as with Prestin, the estimated
      hearing frequencies of whales significantly correlate with numbers of branch-wise
      non-synonymous substitutions in Cldn14, but not with synonymous changes. However,
      in contrast to Prestin, we found no evidence of positive selection in bats. Our
      findings from Cldn14, and comparisons with Prestin, strongly implicate multiple
      loci in the acquisition of echolocation in cetaceans, but also highlight possible
      differences in the evolutionary route to echolocation taken by whales and bats. 

PMID- 23965380
TI  - Menthol inhibits 5-HT3 receptor-mediated currents.
AB  - The effects of alcohol monoterpene menthol, a major active ingredient of the
      peppermint plant, were tested on the function of human 5-hydroxytryptamine type 3
      (5-HT3) receptors expressed in Xenopus laevis oocytes. 5-HT (1 MUM)-evoked
      currents recorded by two-electrode voltage-clamp technique were reversibly
      inhibited by menthol in a concentration-dependent (IC50 = 163 MUM) manner. The
      effects of menthol developed gradually, reaching a steady-state level within 10
      15 minutes and did not involve G-proteins, since GTPgammaS activity remained
      unaltered and the effect of menthol was not sensitive to pertussis toxin
      pretreatment. The actions of menthol were not stereoselective as (-), (+), and
      racemic menthol inhibited 5-HT3 receptor-mediated currents to the same extent.
      Menthol inhibition was not altered by intracellular 1,2-bis(o-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid injections and transmembrane potential changes. The
      maximum inhibition observed for menthol was not reversed by increasing
      concentrations of 5-HT. Furthermore, specific binding of the 5-HT3 antagonist
      [(3)H]GR65630 was not altered in the presence of menthol (up to 1 mM), indicating
      that menthol acts as a noncompetitive antagonist of the 5-HT3 receptor. Finally,
      5-HT3 receptor-mediated currents in acutely dissociated nodose ganglion neurons
      were also inhibited by menthol (100 MUM). These data demonstrate that menthol, at
      pharmacologically relevant concentrations, is an allosteric inhibitor of 5-HT3
      receptors. 

PMID- 23965381
TI  - N-aryl piperazine metabotropic glutamate receptor 5 positive allosteric
      modulators possess efficacy in preclinical models of NMDA hypofunction and
      cognitive enhancement.
AB  - Impaired transmission through glutamatergic circuits has been postulated to play
      a role in the underlying pathophysiology of schizophrenia. Furthermore,
      inhibition of the N-methyl-d-aspartate (NMDA) subtype of ionotropic glutamate
      receptors (NMDAR) induces a syndrome that recapitulates many of the symptoms
      observed in patients with schizophrenia. Selective activation of metabotropic
      glutamate receptor subtype 5 (mGlu5) may provide a novel therapeutic approach for
      treatment of symptoms associated with schizophrenia through facilitation of
      transmission through central glutamatergic circuits. Here, we describe the
      characterization of two novel N-aryl piperazine mGlu5 positive allosteric
      modulators (PAMs): 2-(4-(2-(benzyloxy)acetyl)piperazin-1-yl)benzonitrile
      (VU0364289) and 1-(4-(2,4-difluorophenyl)piperazin-1-yl)-2-((4
      fluorobenzyl)oxy)ethanone (DPFE). VU0364289 and DPFE induced robust leftward
      shifts in the glutamate concentration-response curves for Ca(2+) mobilization and
      extracellular signal-regulated kinases 1 and 2 phosphorylation. Both PAMs
      displayed micromolar affinity for the common mGlu5 allosteric binding site and
      high selectivity for mGlu5. VU0364289 and DPFE possessed suitable pharmacokinetic
      properties for dosing in vivo and produced robust dose-related effects in
      reversing amphetamine-induced hyperlocomotion, a preclinical model predictive of
      antipsychotic-like activity. In addition, DPFE enhanced acquisition of contextual
      fear conditioning in rats and reversed behavioral deficits in a mouse model of
      NMDAR hypofunction. In contrast, DPFE had no effect on reversing apomorphine
      induced disruptions of prepulse inhibition of the acoustic startle reflex. These
      mGlu5 PAMs also increased monoamine levels in the prefrontal cortex, enhanced
      performance in a hippocampal-mediated memory task, and elicited changes in
      electroencephalogram dynamics commensurate with procognitive effects.
      Collectively, these data support and extend the role for the development of novel
      mGlu5 PAMs for the treatment of psychosis and cognitive deficits observed in
      individuals with schizophrenia. 

PMID- 23965382
TI  - Biaryl amides and hydrazones as therapeutics for prion disease in transgenic
      mice.
AB  - The only small-molecule compound demonstrated to substantially extend survival in
      prion-infected mice is a biaryl hydrazone termed "Compd B" (4
      pyridinecarboxaldehyde,2-[4-(5-oxazolyl)phenyl]hydrazone). However, the hydrazone
      moiety of Compd B results in toxic metabolites, making it a poor candidate for
      further drug development. We developed a pharmacophore model based on diverse
      antiprion compounds identified by high-throughput screening; based on this model,
      we generated biaryl amide analogs of Compd B. Medicinal chemistry optimization
      led to multiple compounds with increased potency, increased brain concentrations,
      and greater metabolic stability, indicating that they could be promising
      candidates for antiprion therapy. Replacing the pyridyl ring of Compd B with a
      phenyl group containing an electron-donating substituent increased potency, while
      adding an aryl group to the oxazole moiety increased metabolic stability. To test
      the efficacy of Compd B, we applied bioluminescence imaging (BLI), which was
      previously shown to detect prion disease onset in live mice earlier than clinical
      signs. In our studies, Compd B showed good efficacy in two lines of transgenic
      mice infected with the mouse-adapted Rocky Mountain Laboratory (RML) strain of
      prions, but not in transgenic mice infected with human prions. The BLI system
      successfully predicted the efficacies in all cases long before extension in
      survival could be observed. Our studies suggest that this BLI system has good
      potential to be applied in future antiprion drug efficacy studies. 

PMID- 23965383
TI  - Platelet endothelial cell adhesion molecule targeted oxidant-resistant mutant
      thrombomodulin fusion protein with enhanced potency in vitro and in vivo.
AB  - Thrombomodulin (TM) is a glycoprotein normally present in the membrane of
      endothelial cells that binds thrombin and changes its substrate specificity to
      produce activated protein C (APC) that has antithrombotic and anti-inflammatory
      features. To compensate for loss of endogenous TM in pathology, we have fused
      recombinant TM with single chain variable fragment (scFv) of an antibody to mouse
      platelet endothelial cell adhesion molecule-1 (PECAM). This fusion, anti-PECAM
      scFv/TM, anchors on the endothelium, stimulates APC production, and provides
      therapeutic benefits superior to sTM in animal models of acute thrombosis and
      inflammation. However, in conditions of oxidative stress typical of vascular
      inflammation, TM is inactivated via oxidation of the methionine 388 (M388)
      residue. Capitalizing on the reports that M388L mutation renders TM resistant to
      oxidative inactivation, in this study we designed a mutant anti-PECAM scFv/TM
      M388L. This mutant has the same APC-producing capacity and binding to target
      cells, yet, in contrast to wild-type fusion, it retains APC-producing activity in
      an oxidizing environment in vitro and in vivo. Therefore, oxidant resistant
      mutant anti-PECAM scFv/TM M388L is a preferable targeted biotherapeutic to
      compensate for loss of antithrombotic and anti-inflammatory TM functions in the
      context of vascular oxidative stress. 

PMID- 23965384
TI  - Associations between DGAT1, FABP4, LEP, RORC, and SCD1 gene polymorphisms and fat
      deposition in Spanish commercial beef.
AB  - The objective of the present study was to assess the frequency distribution of
      markers in the diacylglycerol acyltransferase (DGAT1), fatty acid binding protein
      4 (FABP4), leptin (LEP), retinoic acid receptor-related orphan receptor C (RORC),
      and stearoyl-CoA desaturase (SCD1) genes in a Spanish commercial crossbred
      population (n = 286) produced in southwest Spain. We have also evaluated the
      association of these 5 major SNP with backfat thickness (BFT) and intramuscular
      fat (IMF) to use them routinely in the industry (if the associations are
      confirmed) due to their ease of use. The KK genotype of the DGAT1 gene was
      associated (P = 0.046) with the greatest BFT value. Bulls presenting the GG
      genotype for SNP in the FABP4 gene showed greater values for the percentage of
      IMF (P = 0.030), which means an increase of 0.155% IMF per copy of the G allele
      of this marker (P = 0.009). A significant association was found between the RORC:
      g.3290T > G marker and the percentage of IMF. The GG genotype of the RORC:
      g.3290T > G marker showed the lowest IMF percentage (P = 0.025). The specific
      associations found in this study not only provide information about the
      involvement of these genes in the fat deposition at different levels in the
      southwestern Spain cattle population, but can also serve as a tool to improve
      certain meat quality attributes through Marker Assisted Selection. However,
      sensory studies are needed to explore further the usefulness of these genes in
      meat quality and the impact on the actual palatability of the beef. 

PMID- 23965385
TI  - Methodology for quantifying the behavioral activity of dairy cows in freestall
      barns.
AB  - The objectives of this study were to 1) evaluate the validity of automated
      monitoring systems as assessment method for the behavioral activity of dairy cows
      compared with video recording, and 2) determine the sampling intervals required
      to obtain reliable estimates of the daily behavior. To determine lying, standing,
      and walking, 12 cows were equipped with automatic recording devices (IceTag = 12
      cows, HOBO Pendant G = 5 cows), and their behavior was simultaneously recorded
      using a video recording system. The correspondence between the IceTag, HOBO
      logger, and video recording data was analyzed using 2 * 2 contingency tables, and
      we determined the sensitivity, specificity, and predictive value (positive and
      negative). Both types of loggers demonstrated high sensitivity (Sen >= 0.961) and
      specificity (Sp >= 0.951) for lying and standing behaviors with predictive values
      near 1.00. The HOBO logger can accurately describe the laterality of lying
      behavior, whereas the IceTag device inadequately recorded walking, with
      probability predictive values <= 0.303. Daily behaviors of the dairy cows were
      compared for 10 different sampling intervals (1 s, and 1, 2, 3, 4, 5, 10, 15, 30,
      and 60 min) collected by the IceTag, using linear regression. A strong
      relationship (R(2) >= 0.978) was found between the total lying times from data on
      a per-second basis and estimates obtained by 1, 2, 3, 4, 5, 10, and 15 min
      sampling intervals. The sampling intervals of 1 and 2 min were comparable for all
      aspects of lying behavior (R(2) >= 0.813; P > 0.05 for slope = 1, intercept = 0).
      Long sampling intervals (30 and 60 min) showed positive relationship for
      estimating time spent lying and standing (R(2) >= 0.774), but were inappropriate
      for predicting these behaviors, because they lacked accuracy and precision. Both
      the IceTag and HOBO logger accurately measured all aspects of lying and standing
      behavior. Reliable estimates of lying and standing time can be generated using
      relatively short interval lengths (e.g., 3, 4, 5, 10, or 15 min). Shorter
      sampling intervals (<= 2 min) are required to accurately measure aspects of lying
      behavior such as number of lying bouts per day. The automated monitoring systems
      are time- and labor-saving tools that can be used by research or on farm to
      assess cow comfort related to lying behavior. 

PMID- 23965386
TI  - Topical anesthesia mitigates the pain of castration in beef calves.
AB  - Castration involves the removal of the testes and is performed to improve product
      quality and management of male calves. The procedure has been proven to cause
      significant pain and stress, and despite several attempts to reduce the impact of
      castration on animal welfare, there has yet to be a practical and affordable
      option made available for farmer application. To address this issue, we conducted
      2 trials (n = 18 and 27) to examine the efficacy of topical anesthetic Tri-Solfen
      (TA) to alleviate the pain of surgical castration. Angus bull calves (135.8 +/-
      5.7 kg) aged 3 to 4 mo were randomly allocated to 3 treatment groups, including
      surgical castration, castration in combination with TA, and uncastrated controls.
      In Trial 1, pain-related behavior was assessed using a customized numerical
      rating scale (NRS) over 4 h. In Trial 2, pre- and postoperative skin sensitivity
      of the wound and periwound areas was assessed using an electronic von Frey
      anesthesiometer (IITC Life Sciences, Woodland Hills, CA) and von Frey
      monofilaments (300 g). Sampling was repeated at 1 min and 2, 4, 6, and 24 h after
      castration. Pain threshold was measured as maximum pressure (g) exerted by the
      electronic anesthesiometer to invoke animal reflex, and responses to the von Frey
      monofilaments were scored from 0 to 3 using a NRS on the basis of local and
      central motor reflexes. Calves treated with TA displayed significantly less pain
      related behaviors up to 3.5 h after castration than untreated calves (P < 0.001)
      and did not differ from uncastrated controls. Topical anesthetic-treated calves
      also exhibited significantly greater pain threshold of the wound (559.2 +/- 14.3
      g) and surrounding skin (602.8 +/- 16.5 g) than untreated calves (446.0 +/- 18.9
      and 515.3 +/- 20.4 g, respectively; P < 0.001). Control and TA-treated calves had
      significantly lower mean response scores to von Frey stimulation than untreated
      calves (0.333, 0.978, and 4.289, respectively; P < 0.001). Results indicate that
      TA effects rapid and prolonged pain alleviation in calves up to 24 h after
      castration. Topical anesthesia may present a cost-effective, practical, on-farm
      approach to pain alleviation and is proposed as a potential tool for reducing the
      welfare impact on the beef animal in routine husbandry procedures. 

PMID- 23965387
TI  - Effects of composite antimicrobial peptides in weanling piglets challenged with
      deoxynivalenol: I. Growth performance, immune function, and antioxidation
      capacity.
AB  - The mycotoxin deoxynivalenol (DON) is a food contaminant that leads to reduced
      feed intake and reduced BW gain, as well as organ impairment. On the other hand,
      antimicrobial peptides have been shown to have positive effects on growth
      performance, nutrient digestibility, and immune function. The purpose of this
      study was to investigate the protective effects of composite antimicrobial
      peptides (CAP) on piglets challenged with DON. After a 7-d adaptation period, 28
      individually housed piglets (Duroc * Landrace * Large Yorkshire) weaned at 28 d
      of age were randomly assigned to receive 1 of 4 treatments (7 pigs/treatment):
      negative control, basal diet (NC), basal diet + 0.4% CAP (CAP), basal diet + 4
      mg/kg DON (DON), and basal diet + 4 ppm DON + 0.4% CAP (DON + CAP). On d 15 and
      30 after the initiation of treatment, blood samples were collected for the
      determination of blood profile. Piglets were monitored for 30 d to assess
      performance and then were slaughtered to obtain organs for the determination of
      the relative weight of organs. The results showed that dietary supplementation
      with DON decreased (P < 0.05) ADFI, ADG, and G:F, whereas dietary supplementation
      with CAP improved ADG and G:F (P < 0.05). The relative weight of the kidney and
      pancreas was greater and the relative weight of the spleen was lighter in the DON
      treatment than in the other 3 treatments (P < 0.05). There were no effects (P >
      0.05) on other relative weights of viscera, except the relative weight of the
      gallbladder, but the diamine oxidase activity in the liver decreased in DON
      treated piglets (P < 0.05). Piglets in the DON treatment had increased serum
      concentrations of alkaline phosphatase, alanine transaminase, and aspartate
      aminotransferase and a dramatic decrease in total protein (P < 0.05), whereas
      there were no differences (P > 0.05) between the DON + CAP treatment and the
      other treatments. The DON treatment decreased the numbers of red blood cells and
      platelets, as well as the serum catalase concentrations, and decreased the serum
      concentrations of H2O2, maleic dialdehyde, and nitric oxide (P < 0.05). The
      numbers of platelets and thrombocytocrit, as well as the serum concentrations of
      catalase, were greater, whereas the maleic dialdehyde concentrations were
      decreased, in both the CAP and DON + CAP treatments compared with the other
      treatments (P < 0.05). Compared with the control treatment, DON decreased
      peripheral lymphocyte proliferation on d 15, whereas supplementation with CAP
      increased it on d 15 and 30 (P < 0.05). These findings indicate that CAP could
      improve feed efficiency, immune function, and antioxidation capacity and
      alleviate organ damage, and thus, it has a protective effect in piglets
      challenged with DON. 

PMID- 23965388
TI  - Nutritional intervention in early life to manipulate rumen microbial colonization
      and methane output by kid goats postweaning.
AB  - The growing interest in reducing methane (CH4) emissions from ruminants by
      dietary means is constrained by the complexity of the microbial community in the
      rumen of the adult animal. The aim of this work was to study whether intervention
      in early life of goat kids has an impact on methane emissions and the microbial
      ecosystem in the rumen and whether the effects persist postweaning. Sixteen doe
      goats giving birth to 2 kids each were randomly split into 2 experimental groups:
      8 does were treated (D+) with bromochloromethane (BCM) after giving birth and
      over 2 mo, and the other 8 does were not treated (D-). In both groups of does, 1
      kid per doe was treated with BCM (k+) for 3 mo, and the other was untreated (k-),
      resulting in 4 experimental groups: D+k+, D+k-, D-k+, and D-k-. Methane emissions
      were recorded, and ruminal samples were collected from kids at 2 mo of age
      (weaning, W) and 1 (W+1) and 4 (W+4) mo later. At W+1 mo, CH4 emissions by k+
      kids were 52% and 59% less than untreated kids (in D+ and D- groups,
      respectively). However, at W+4 mo, only D+k+ kids remained lower (33%) emitters
      and exhibited greater daily BW gain (146 g/d) compared with the other 3 groups
      (121.8 g/d). The analysis of the archaeal community structure by Denaturing
      Gradient Gel Electrophoresis (DGGE)showed a strong effect of BCM treatment on
      does and kids that persisted only in D+k+ kids. The study showed that the
      application of BCM during early life of kids modified the archaeal population
      that colonized the rumen, which resulted in decreased CH4 emissions around
      weaning. The effect is influenced by the treatment applied to the doe and
      persisted 3 mo later in D+k+ kids. 

PMID- 23965389
TI  - Enteric methane production from beef cattle that vary in feed efficiency.
AB  - We hypothesized that CH4 production will decrease with increased feed efficiency.
      Two experiments were conducted to determine CH4 production of cattle that
      differed in feed efficiency. Cattle in both studies were selected from larger
      contemporary groups. Animals furthest from the confidence ellipse that resulted
      from regressing BW gain on DMI were selected. In the first experiment, 113
      crossbred steers were evaluated for feed efficiency for 64 d. Steers were 355 +/-
      1 d of age and weighed 456 +/- 10 kg when they began the study. Steers were fed a
      ration that consisted of (DM basis) 82.8% corn, 12.8% corn silage, and 4.5%
      supplement [contains 0.065% monensin, 32% CP (28% NPN), 7.5% Ca, 0.8% P, 4.8%
      NaCl, 1.8% K, and 55,116 IU/kg vitamin A]. Thirty-seven steers were selected to
      measure CH4 production. In the second experiment, 197 heifers were evaluated for
      feed efficiency for 64 d. Heifers were 286 +/- 1 d of age and weighed 327 +/- 2
      kg when they began the study. Heifers were fed a ration that consisted of (DM
      basis) 60% corn silage, 30% alfalfa hay, and 10% wet distillers grains with
      solubles. Forty-seven heifers were selected to measure CH4 production. Methane
      production was measured with respiration calorimeters. In both experiments,
      cattle had ad libitum access to feed, and DMI consumed during the 24 h before CH4
      production was measured. Methane production was collected for a 6-h period on
      untrained cattle. Consequently, methane production is not a quantitative measure
      of daily methane production; rather, it is an index value to rank cattle.
      Multiple regression analysis was used to determine the relationship between
      either BW gain:DMI ratio or residual feed intake (RFI) on CH4 production after
      adjusting for the previous 24-h DMI. In the steers, BW gain:DMI ratio and
      previous 24-h feed intake accounted for little of the variance in CH4 production
      (R(2) = 0.009), and neither did RFI and previous 24-h feed intake (R(2) = 0.001).
      In the heifers, the BW gain:DMI ratio contributed 28% toward the variance
      estimate and previous 24-h DMI contributed 72% toward the variance estimate (R(2)
      = 0.31). As the BW gain:DMI ratio increased, daily CH4 production increased. The
      regression coefficient for RFI (P = 0.45) did not differ from 0 for CH4
      production. Our study does not support our original hypothesis that CH4
      production decreases with increased feed efficiency and suggests that CH4
      production may increase with increased feed efficiency. 

PMID- 23965390
TI  - Effects of tail docking and teeth clipping on the physiological responses,
      wounds, behavior, growth, and backfat depth of pigs.
AB  - The objective of this experiment was to compare the effects of tail docking and
      teeth clipping on the growth and behavior of pigs. Pigs (n = 126) from 21 litters
      (6 pigs/litter) were blocked by birth weight, and assigned at 3 d of age within
      blocks to either teeth clipping and tail docking (processed) or control (sham
      processed). Vocalizations of pigs were recorded during the procedures, and
      behavior was observed during the lactation, nursery, and growing periods. Blood
      samples were collected on d 21 to measure serum IgG concentrations. Wounds on the
      body and tail were assessed by inspecting both sides of the body and tail at 70,
      110, and 160 d of age, whereas BW were recorded at 10, 21, 70, and 160 d of age.
      Fat and LM depths were measured ultrasonically on growing pigs at 160 d of age.
      Clipped and docked pigs vocalized more (1.06 vs. 0.62 s; P < 0.01) during
      processing, and processed pigs were observed lying alone more often (P = 0.03)
      during the 3 d after processing and the entire suckling period; however, teeth
      clipping and docking did not (P >= 0.14) alter the frequency that pigs spent
      suckling, standing, huddling, playing/fighting, or sitting during the first 3 d
      or between 5 and 15 d after processing. Social behavior during the nursery (P >=
      0.23) and grower phases (P >= 0.18) was unaffected by clipping and docking, but
      processed pigs rested more (P = 0.03) during the nursery period and were less (P
      <= 0.01) interested in exploratory behaviors during both phases, especially
      during pen (P <= 0.04) and enrichment investigations (P <= 0.02). Teeth clipping
      and tail docking reduced ADG between 10 and 21 d (P = 0.01) and 21 to 70 d of age
      (P = 0.04), resulting in lighter BW at 21 (P = 0.01) and 70 d of age (P = 0.08)
      compared with sham-processed pigs. However, 160-d BW (P = 0.62), d 70 to 160 ADG
      (P = 0.23), and G:F (P >= 0.15) were not affected by teeth clipping and tail
      docking. Additionally, there was no difference between sham and processed pigs
      for fat depth (P >= 0.05), LM depth (P = 0.93), or estimated percent muscle (P =
      0.27). Even though tail docking and teeth clipping appear to produce short-term
      pain and distress, results of this experiment indicate that leaving the teeth and
      tails intact have no detrimental effects on mortality, morbidity, live
      performance, or carcass merit of growing-finishing pigs. 

PMID- 23965392
TI  - Effects of composite antimicrobial peptides in weanling piglets challenged with
      deoxynivalenol: II. Intestinal morphology and function.
AB  - Deoxynivalenol (DON) affects animal and human health and targets the
      gastrointestinal tract. The objective of this study was to evaluate the ability
      of composite antimicrobial peptides (CAP) to repair intestinal injury in piglets
      challenged with DON. A total of 28 piglets (Duroc * Landrace * Large Yorkshire)
      weaned at 28 d of age were randomly assigned to receive 1 of 4 treatments (7
      pigs/treatment): negative control, basal diet (NC), basal diet + 0.4% composite
      antimicrobial peptide (CAP), basal diet + 4 mg/kg DON (DON), and basal diet + 4
      mg/kg DON + 0.4% CAP (DON + CAP). After an adaptation period of 7 d, blood
      samples were collected on d 15 and 30 after the initiation of treatment for
      determinations of the concentrations of D-lactate and diamine oxidase. At the end
      of the study, all piglets were slaughtered to obtain small intestines for the
      determination of intestinal morphology, epithelial cell proliferation, and
      protein expression in the mammalian target of rapamycin (mTOR) signaling pathway.
      The results showed that DON increased serum concentrations of D-lactate and
      diamine oxidase, and these values in the CAP and DON + CAP treatments were less
      than those in the NC and DON treatments, respectively (P < 0.05). The villous
      height/crypt depth in the jejunum and ileum and the goblet cell number in the
      ileum in the CAP and DON + CAP treatments were greater than those in the NC and
      DON treatments (P < 0.05). The proliferating cell nuclear antigen (PCNA) labeling
      indexes for the jejunum and ileum in the DON + CAP treatment were greater than
      those in the DON treatment (P < 0.05). The DON decreased (P < 0.05) the relative
      protein expression of phosphorylated Akt (Protein Kinase B) and mTOR in the
      jejunal and ileal mucosa and of phosphorylated 4E-binding protein 1 (p-4EBP1) in
      the jejunal mucosa, whereas CAP increased (P < 0.05) the protein expression of p
      4EBP1 in the jejunum. These findings showed that DON could enhance intestinal
      permeability, damage villi, cause epithelial cell apoptosis, and inhibit protein
      synthesis, whereas CAP improved intestinal morphology and promoted intestinal
      epithelial cell proliferation and protein synthesis, indicating that CAP may
      repair the intestinal injury induced by DON. 

PMID- 23965393
TI  - Effect of graded levels of fiber from alfalfa meal on intestinal nutrient and
      energy flow, and hindgut fermentation in growing pigs.
AB  - The objective of this experiment was to determine the effects of fiber level from
      alfalfa meal and collection period on intestinal nutrient and energy flow, and
      hindgut fermentation in growing pigs. Twenty-four pigs (initial BW = 21.4 +/- 1.5
      kg) were prepared by T-cannula insertion into the distal ileum and allotted to 4
      treatments. The pigs were provided a corn-soybean meal control diet or a diet in
      which corn and soybean meal were partly replaced by 5%, 10%, or 20% alfalfa meal
      to give the graded levels of dietary fiber during two 10-d collection periods.
      The BW of pigs at the start of periods 1 and 2 were 32.2 +/- 2.4 and 37.7 +/- 4.2
      kg, respectively. The final BW at the end of period 2 was 46.8 +/- 4.0 kg. The
      apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD)
      of nutrients and energy were measured. The VFA concentration was also determined
      in the ileal and fecal samples. Nutrient digestibility was not affected by
      inclusion of 5% alfalfa meal in the diet. The AID, ATTD, and hindgut fermentation
      of DM, carbohydrates (CHO), and GE decreased (linear, P < 0.05) as the level of
      alfalfa meal in the diet increased. The intestinal flow of DM, CHO, ADF, and GE
      increased (linear, P < 0.05) by increasing the level of dietary alfalfa. The pH
      in ileal digesta and concentration of acetate, propionate, and total VFA in the
      feces increased (linear, P < 0.01) as the level of alfalfa meal in the diet
      increased. From experiment period 1 to 2, ATTD and hindgut fermentation of CHO
      decreased (P < 0.01), whereas concentrations of propionate, valerate, and total
      VFA in ileal samples increased (P < 0.05). A multiple linear regression analysis,
      taking into account both soluble dietary fiber and insoluble dietary fiber
      intake, explained the variation (P < 0.01) in total tract flow of NDF (93%), ADF
      (84%), GE (73%), DM (71%), and CHO (62%). In conclusion, the diet containing 5%
      of alfalfa meal did not affect nutrient and energy digestion. Intestinal flow of
      CHO decreased during the 10-d collection period. The VFA concentration increased
      with fiber level and 10-d exposure to the experimental diets. Soluble and
      insoluble fibers from alfalfa meal have differential roles in nutrient digestion,
      which may help explain the variation observed in the intestinal flow of
      nutrients. 

PMID- 23965394
TI  - Technical note: whole-pen assessments of nutrient excretion and digestibility
      from dairy replacement heifers housed in sand-bedded freestalls.
AB  - Our objectives were to describe and test refined procedures for quantifying
      excreta produced from whole pens of dairy heifers. Previous research efforts
      attempting to make whole-pen measurements of excreta output have been complicated
      by the use of organic bedding, which requires cumbersome analytical techniques to
      quantify excreta apart from the bedding. Research pens equipped with sand-bedded
      freestalls offer a unique opportunity for refinement of whole-pen fecal
      collection methods, primarily because sand-bedded freestall systems contain no
      organic bedding; therefore, concentrations of ash within the manure, sand, and
      feces can be used to correct for contamination of manure by sand bedding. This
      study was conducted on a subset of heifers from a larger production-scale feeding
      trial evaluating ensiled eastern gamagrass [Tripsacum dactyloides (L.) L.]
      haylage (EGG) that was incorporated into a corn silage/alfalfa haylage-based
      blended diet at rates of 0, 9.1, 18.3, or 27.4% of total DM. The diet without EGG
      also was offered on a limit-fed basis. Eighty Holstein dairy heifers were blocked
      (heavy weight, 424 +/- 15.9 kg; light weight, 324 +/- 22.4 kg) and then assigned
      to 10 individual pens containing 8 heifers/pen. One pen per block was assigned to
      each of the 5 research diets, and whole-pen fecal collections were conducted
      twice for each pen. Grab fecal samples also were gathered from individual heifers
      within each pen, and subsequent analysis of these whole-pen composites allowed
      reasonable estimates of OM and NDF excreta output. Under the conditions of our
      experimental design, pooled SEM for the excreta DM, OM, NDF, and NDF (ash
      corrected) output were 0.113, 0.085, 0.093, and 0.075 kg.heifer(-1).d(-1),
      respectively. For DM excretion, this represented about one-third of the SEM
      reported for previous whole-pen collections from bedded-pack housing systems.
      Subsequent calculations of apparent DM and OM digestibilities indicated that the
      technique was sensitive, and linear trends (P <= 0.027) associated with the
      inclusion rates of EGG within the diet were detected. This technique allows
      estimation of apparent diet digestibilities on multiple animals simultaneously,
      thereby mitigating the need for isolating individual animals to obtain
      digestibility coefficients. The approach appears viable but requires hand labor
      for collections of multiple pens and thorough mixing of large volumes of manure
      as well as analytical corrections for sand ingested by lounging heifers. 

PMID- 23965395
TI  - Influence of dental correction on nociceptive test responses, fecal appearance,
      body condition score, and apparent digestibility coefficient for dry matter of
      Zamorano-leones donkeys (Equus asinus).
AB  - The influence of dental correction on nociceptive (pressure) test responses,
      fecal appearance, BCS, and apparent digestibility coefficient for DM was studied
      in 18 Zamorano-Leones donkeys, an endangered local breed from the Zamora province
      in Spain. For this purpose, donkeys were divided into 2 homogeneous control and
      treatment groups, based on age, BCS, and dental findings. On d 1, 45, 90, and
      135, BCS and nociceptive test responses were evaluated in all donkeys. Feed and
      fecal samples were collected from all donkeys for 3 consecutive days, starting at
      each of the aforementioned days. Apparent digestibility coefficient for DM was
      estimated, using ADL as an internal marker. A progressive decrease of positive
      nociceptive test responses was observed from d 1 up to 90 (P < 0.01) in the
      treatment group. No difference between groups was observed for BCS. However, BCS
      at d 90 was greater (P = 0.018) than observed on d 1 or 45, indicating a time
      influence. Concerning apparent digestibility coefficient for DM, there were
      differences among collection days in apparent digestibility coefficient for DM (P
      < 0.05). No differences in fecal appearance were observed between treatments or
      collection days. This study highlighted the importance of regular dental care for
      not only Zamorano-Leones donkeys but also the equid population, in general, to
      improve their welfare. 

PMID- 23965397
TI  - Proximal Myopathy: A Rare Presentation of Celiac Disease.
AB  - Celiac disease presenting as proximal myopathy is rarely seen, particularly in
      children. We report a 5-year-old girl who presented with bilateral lower limb
      weakness and on examination had proximal myopathy. She also had florid rickets
      and short stature. On investigation, the underlying etiology turned out to be
      celiac disease. Proximal myopathy with celiac disease can be secondary to the
      disease per se or due to associated osteopenia and rickets.

PMID- 23965396
TI  - BMS-927711 for the acute treatment of migraine: a double-blind, randomized,
      placebo controlled, dose-ranging trial.
AB  - BACKGROUND: BMS-927711 is a potent, selective, competitive human calcitonin gene
      related peptide (CGRP) receptor antagonist that has shown in vivo efficacy
      without vasoconstrictor effect. The objective of the current study was to
      determine an effective and tolerable dose range of BMS-927711 for the acute
      treatment of migraine. METHODS: In this randomized, double-blind, placebo
      controlled, dose-ranging study, 885 patients were randomized using an adaptive
      design to one of the following dose groups: BMS-927711 (10, 25, 75, 150, 300, or
      600 mg); sumatriptan 100 mg (active comparator); and placebo. Patients were
      treated for a single migraine attack. The primary endpoint was pain freedom at
      two hours post-dose. RESULTS: Of patients who took the study drug, 799 had one
      post-randomization efficacy evaluation. Significantly more patients in the BMS
      927711 75 mg (31.4%, P = 0.002), 150 mg (32.9%, P < 0.001), and 300 mg (29.7%, P
      = 0.002) groups and the sumatriptan group (35%, P < 0.001) had pain freedom at
      two hours post-dose versus placebo (15.3%). For the secondary endpoint of
      sustained pain freedom from two to 24 hours post-dose, BMS-927711 doses (25-600
      mg) were also statistically significant compared with placebo. No deaths or
      treatment-related serious adverse events (AEs) were reported, and no patients
      discontinued because of AEs. CONCLUSIONS: BMS-927711 is superior to placebo at
      several different doses (75 mg, 150 mg, and 300 mg) and has an excellent
      tolerability profile.

PMID- 23965398
TI  - Botulinum toxin type A in children and adolescents with severe cerebral palsy: a
      retrospective chart review.
AB  - This retrospective cohort study reviewed set goals and their outcomes of children
      and adolescents with severe cerebral palsy who received botulinum toxin A in 2008
      and 2009. Sixty children (36 male, mean age 9 years) were included. They received
      on average 4 (range 1-7) treatments, with the dosage varying between 20 and 400
      units per treatment (3-21 U/kg/body weight). Mild transient side effects were
      reported in 12 of 242 treatments with botulinum toxin A. Treatment goals were
      related to lower limb function (82%), range of motion (68%), positioning (33%),
      upper limb function (33%), and facilitating ease of care in dressing (30%),
      toileting, and diapering (22%). The treatment goals were reached in 60% to 85% by
      report of the parent and child dyad. Our findings suggest that botulinum toxin A
      should be considered as a treatment option in patients with cerebral palsy within
      Gross Motor Function Classification System levels IV and V. 

PMID- 23965399
TI  - Melanotic neuroectodermal tumor of infancy arising in the temporal bone.
AB  - Melanotic neuroectodermal tumor of infancy is a rare melanin-containing neoplasm
      with locally aggressive and rapid expansile growth, usually involving the
      maxilla, skull, and mandible of early infancy. Radical surgery is critical for a
      long-term outcome. We present a case of 14-month-old girl with rapid-growing
      subcutaneous mass arising in the right temporal bone and extending intracranially
      on computed tomographic scan. Radical surgery was performed. A brownish-black
      tumor composed of large pigmented epithelioid cells, positive for cytokeratins
      and HMB-45, and nests of small neuroblast-like cells positive for neuron-specific
      enolase and synaptophysin, was diagnosed as melanotic neuroectodermal tumor of
      infancy. The patient remained well without evidence of recurrence for 1 year
      after surgery. Clinicopathological features, management alternatives and outcome
      were discussed. 

PMID- 23965400
TI  - Speed-accuracy testing on the Apple iPad provides a quantitative test of upper
      extremity motor performance in children with dystonia.
AB  - The currently available scales for quantitative measurement of the severity of
      childhood dystonia require human observer ratings and provide poor granularity in
      the scores for individual limbs. We evaluated the use of new-generation high
      quality touchscreens (an iPad) according with the Fitts law, which is a
      mathematical model that takes into account the relation between movement time and
      the task accuracy. We compared the abilities of healthy subjects and children
      with dystonia. The linear relation described by Fitts law held for all the
      groups. The movement time and the information transmitted were age and severity
      related. Our results provide evidence for the usability and validity of using
      Fitts law as a quantitative diagnostic tool in children with dystonia.
      Furthermore, testing on touchscreen tablets may help to guide the design of user
      interfaces to maximize the communication rate for children who depend upon
      assistive communication devices.

PMID- 23965401
TI  - Ion track reconstruction in 3D using alumina-based fluorescent nuclear track
      detectors.
AB  - Fluorescent nuclear track detectors (FNTDs) based on Al2O3: C, Mg single crystal
      combined with confocal microscopy provide 3D information on ion tracks with a
      resolution only limited by light diffraction. FNTDs are also ideal substrates to
      be coated with cells to engineer cell-fluorescent ion track hybrid detectors
      (Cell-Fit-HD). This radiobiological tool enables a novel platform linking cell
      responses to physical dose deposition on a sub-cellular level in proton and heavy
      ion therapies. To achieve spatial correlation between single ion hits in the cell
      coating and its biological response the ion traversals have to be reconstructed
      in 3D using the depth information gained by the FNTD read-out. FNTDs were coated
      with a confluent human lung adenocarcinoma epithelial (A549) cell layer. Carbon
      ion irradiation of the hybrid detector was performed perpendicular and angular to
      the detector surface. In situ imaging of the fluorescently labeled cell layer and
      the FNTD was performed in a sequential read-out. Making use of the trajectory
      information provided by the FNTD the accuracy of 3D track reconstruction of
      single particles traversing the hybrid detector was studied. The accuracy is
      strongly influenced by the irradiation angle and therefore by complexity of the
      FNTD signal. Perpendicular irradiation results in highest accuracy with error of
      smaller than 0.10 degrees . The ability of FNTD technology to provide accurate 3D
      ion track reconstruction makes it a powerful tool for radiobiological
      investigations in clinical ion beams, either being used as a substrate to be
      coated with living tissue or being implanted in vivo. 

PMID- 23965402
TI  - Dysfunctional chemosensation in myasthenia gravis: a systematic review.
AB  - OBJECTIVES: Myasthenia gravis has traditionally been viewed as a disorder that
      solely affects the neuromuscular junction within the peripheral nervous system.
      However, there is now evidence that the cholinergic dysfunction of this disorder
      may be more widespread than previously believed. This article provides a
      systematic review of the studies that examined smell and taste function in
      myasthenia gravis. METHODS: We analyzed studies that reported chemosensory
      function alterations in patients with myasthenia gravis. PubMed, MEDLINE, Web of
      Science, EMBASE, and SciELO, searched to identify articles published from January
      1950 through December 2012, were supplemented by relevant articles. The following
      information was identified from each article: the number of patients, number of
      controls (if any), clinical stage of patients, neurological involvement,
      serological state, taste or smell involvement, chemosensory test used, and
      country of publication. RESULTS: Ten studies reporting smell and taste function
      and dysfunction in patients with myasthenia gravis were identified, most of which
      were case reports commenting on apparent abnormalities in the taste system. The
      sole empirical study that investigated taste function, however, was negative,
      suggesting that some reports of taste loss may reflect olfactory loss. One study
      clearly documented olfactory dysfunction in patients with myasthenia gravis,
      dysfunction most likely attributable to altered central nervous system
      cholinergic function. CONCLUSIONS: Chemosensory dysfunction has been reported in
      a number of patients with myasthenia gravis. Given the close association between
      complaints of taste dysfunction and loss of flavor sensations secondary to
      olfactory system damage, quantitative testing should be used to accurately assess
      the nature and degree of the dysfunction present in this debilitating disorder.

PMID- 23965403
TI  - Leg amyotrophic diplegia: prevalence and pattern of weakness at US neuromuscular
      centers.
AB  - OBJECTIVE: To identify the frequency of leg amyotrophic diplegia (LAD) at a US
      academic center, describe the pattern of weakness, and provide comparative data
      from 8 additional major US academic institutions. BACKGROUND: LAD is a leg onset
      variant of progressive muscular atrophy (PMA). LAD weakness is confined to the
      legs for at least 2 years, and there are no upper motor neuron signs.
      DESIGN/METHODS: We present a retrospective chart review of 24 patients with the
      LAD presentation from the University of Kansas Medical Center ( n = 8 cases) and
      from 8 US academic institutions (n = 16 cases). RESULTS: Of the 318 subjects
      identified in the University of Kansas Medical Center Neuromuscular Research
      Database, 82% (260 subjects) had amyotrophic lateral sclerosis (ALS), 1.9% (6)
      had familial ALS, 6.6% (21) had primary lateral sclerosis, and 9.2% (29) had
      lower motor neuron (LMN) disease. Of these 29 cases, 16 had PMA, 5 had brachial
      amyotrophic diplegia, while 8 had LAD. The mean LAD age of onset was 58 years
      with a male/female ratio of 3/1. Onset was asymmetric in 7/8. We identified a
      pelviperoneal pattern of weakness (sparing of knee extension and/or ankle plantar
      flexion) in 4 cases and distal predominant weakness in 3 cases. All patients had
      electrodiagnostic findings consistent with motor neuron disease confined to the
      lower extremities. We present LAD disease duration and survival data from 8 major
      academic neuromuscular centers. At last follow-up, weakness progressed to involve
      the arms in 6/24 LAD cases and of these 6 cases, 2 patients died from progression
      to typical ALS. From onset of symptoms, mean survival in LAD is 87 months, with
      92% of cases being alive. CONCLUSIONS/RELEVANCE: The natural history of LAD
      differs from typical forms of ALS and PMA. LAD is a slowly progressive disorder
      that accounts for a fourth of LMN disease cases. An asymmetric pelviperoneal
      pattern of weakness should heighten the suspicion for LAD.

PMID- 23965404
TI  - A case of severe chronic progressive axonal polyradiculoneuropathy temporally
      associated with anti-CV2/CRMP5 antibodies.
AB  - OBJECTIVES: The involvement of the peripheral nervous system by anti-CV2/CRMP5
      paraneoplastic antibodies is typically encountered as a mixed sensorimotor
      polyneuropathy. We report a fatal case of severe chronic progressive axonal
      polyradiculoneuropathy in association with this antibody. METHODS: Review of the
      patient's chart, nerve conduction/electromyographic studies, and nerve biopsy.
      RESULTS: A 51-year-old man presented with a progressive quadriparesis over a 4
      month period. Extensive evaluation for potential etiologies was significant only
      for positive anti-CV2/CRMP5 antibodies without detection of an underlying
      neoplasm. Despite multiple immunomodulatory therapies, the patient progressed and
      demonstrated electrodiagnostic evidence for a chronic axonal
      polyradiculoneuropathy with ongoing denervation. The patient eventually died of
      respiratory failure. CONCLUSIONS: This case adds to the clinical spectrum of the
      peripheral nervous system involvement in patients with paraneoplastic anti
      CV2/CRMP5 antibodies.

PMID- 23965406
TI  - Brachial plexus injury associated with extracorporeal membrane oxygenation.
AB  - INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary
      support system. We present 2 patients of ECMO-related brachial plexus injury.
      METHODS: Patients were selected from a registry of 154 patients treated with ECMO
      from January 2002 to September 2011. RESULTS: Five patients had unilateral arm
      weakness after the initiation of ECMO therapy. There was no neurological
      examination or electrophysiological testing data available for 3 patients.
      Diagnosis of brachial plexus injury was confirmed in 2 patients, one based on
      neurological examination and one based on electrophysiological testing.
      DISCUSSION: Axillary artery cannulation resulting in hematoma formation was
      identified as a probable risk factor for brachial plexus injury in our 2
      patients.

PMID- 23965405
TI  - Patient identification of the symptomatic impact of charcot-marie-tooth disease
      type 1A.
AB  - OBJECTIVE: The burden of Charcot-Marie-Tooth type 1A (CMT1A), the most common
      inherited peripheral neuropathy, including impact on patient quality of life
      (QOL) is not well understood. This study aims to qualitatively describe the range
      of symptoms associated with CMT1A and impact on QOL. METHODS: We performed
      qualitative interviews with 16 adult CMT1A patients. Each interview was analyzed
      using a qualitative framework technique to identify and index symptoms by theme.
      RESULTS: Sixteen patients provided 656 quotes. One hundred forty-five symptoms of
      importance were identified representing 20 symptomatic themes. Symptoms
      associated with difficulty with mobility and ambulation, specific activity
      impairment, and emotional distress were the most frequently mentioned.
      CONCLUSIONS: Multiple symptoms contribute to CMT1A disease burden, some
      previously underrecognized. Improved recognition of underrecognized symptoms will
      optimize patient care and QOL.

PMID- 23965407
TI  - Hereditary neuropathy with liability to pressure palsy: two cases of difficult
      diagnosis.
AB  - Hereditary neuropathy with liability to pressure palsies (HNPP) is an inherited
      autosomal dominant disorder that causes a polyneuropathy with predisposition for
      involvement at sites of compression and is often underdiagnosed or misdiagnosed
      due to its heterogeneity in clinical and electrophysiological presentation. We
      report 2 cases of HNPP, which were initially diagnosed and treated as either an
      acquired demyelinating disorder or alternative inherited demyelinating disorder.
      Thorough evaluation of repeat electrodiagnostic studies and genetic testing
      confirmed the diagnosis of HNPP in both cases. One case showed the classic
      peripheral myelin protein 22 (PMP22) deletion and the other case showed a
      previously reported single base pair deletion at Leu145 causing a frameshift
      mutation at the PMP22 gene. These cases underscore the difficulty of diagnosing
      HNPP, because of the variations in clinical and electrophysiological findings and
      reinforce the importance of a combination high index of clinical suspicion,
      electrodiagnostic testing, and genetic testing to make the diagnosis. 

PMID- 23965408
TI  - What's in the literature?
AB  - In amyotrophic lateral sclerosis (ALS), a recent double-blind placebo-controlled
      trial of acetyl-L-carnitine along with riluzole showed probable benefit in 42
      patients compared with 40 patients who received placebo. Using an
      electrophysiologic measure devised to differentiate ALS from other neuromuscular
      conditions, a "splint-hand index" was devised and is reviewed. Analysis of skin
      in ALS may also be of interest, and there was a report of accumulation of fused
      in sarcoma protein in the epidermis of ALS patients. With regard to myasthenia
      gravis, there is another report that early treatment of ocular symptoms with
      corticosteroids may prevent the development of generalized symptoms. A new study
      of thymus histopathology in muscle-specific tyrosine kinase (MuSK) myasthenia
      gravis is covered and another article on the use of thymectomy. In Duchenne
      muscular dystrophy, the best method of administrating corticosteroids is still
      being debated, and a long-term study of daily versus intermittent prednisolone is
      reviewed. The study showed less sustained benefit from the intermittent
      prednisolone but with a better side effect profile. According to 2 recent
      reports, it seems that titin mutations may be an underrecognized cause of
      myopathy with early respiratory failure in adults. Keeping with the respiratory
      failure theme, there was also an interesting article on the long-term benefits
      and side effects of cyclosporine in patients with interstitial lung disease from
      antisynthetase syndrome. Finally, the spectrum of small fiber neuropathy may be
      expanding to include a causative role in some patients with fibromyalgia syndrome
      and in juveniles with diffuse pain and a possible autoimmune predisposition. 

PMID- 23965410
TI  - Microfluidic hydrothermal growth of ZnO nanowires over high aspect ratio
      microstructures.
AB  - A hydrothermal synthesis of densely packed ZnO nanowires was realized in a
      confined space via forced circulation of the heated growth solution through
      microfluidic channels formed primarily by a set of high aspect ratio trenches in
      a Si substrate. A uniform and conformal seeding layer of ZnO was deposited to
      cover the entire surface of the trenches by means of atomic layer deposition
      (ALD). Densely packed ZnO nanowires were formed inside the trenches with
      particularly good coverage over the sidewalls, where they would not grow
      effectively through a conventional hydrothermal method. The strategy for
      controlled growth of densely packed ZnO nanowires over such high aspect ratio
      microstructures is deemed beneficial when these microstructures are employed as
      electrodes with high specific surface areas for devices such as supercapacitors
      or any other electrochemical devices. 

PMID- 23965409
TI  - Correlations in timing of sodium channel expression, epilepsy, and sudden death
      in Dravet syndrome.
AB  - Dravet Syndrome (DS) is an intractable genetic epilepsy caused by loss-of
      function mutations in SCN1A, the gene encoding brain sodium channel Nav 1.1. DS
      is associated with increased frequency of sudden unexpected death in humans and
      in a mouse genetic model of this disease. Here we correlate the time course of
      declining expression of the murine embryonic sodium channel Nav 1.3 and the rise
      in expression of the adult sodium channel Nav 1.1 with susceptibility to
      epileptic seizures and increased incidence of sudden death in DS mice. Parallel
      studies with unaffected human brain tissue demonstrate similar decline in Nav 1.3
      and increase in Nav 1.1 with age. In light of these results, we introduce the
      hypothesis that the natural loss Nav 1.3 channel expression in brain development,
      coupled with the failure of increase in functional Nav 1.1 channels in DS,
      defines a tipping point that leads to disinhibition of neural circuits,
      intractable seizures, co-morbidities, and premature death in this disease. 

PMID- 23965411
TI  - A hybrid atomistic electrodynamics-quantum mechanical approach for simulating
      surface-enhanced Raman scattering.
AB  - Surface-enhanced Raman scattering (SERS) is a technique that has broad
      implications for biological and chemical sensing applications by providing the
      ability to simultaneously detect and identify a single molecule. The Raman
      scattering of molecules adsorbed on metal nanoparticles can be enhanced by many
      orders of magnitude. These enhancements stem from a twofold mechanism: an
      electromagnetic mechanism (EM), which is due to the enhanced local field near the
      metal surface, and a chemical mechanism (CM), which is due to the adsorbate
      specific interactions between the metal surface and the molecules. The local
      field near the metal surface can be significantly enhanced due to the plasmon
      excitation, and therefore chemists generally accept that the EM provides the
      majority of the enhancements. While classical electrodynamics simulations can
      accurately simulate the local electric field around metal nanoparticles, they
      offer few insights into the spectral changes that occur in SERS. First-principles
      simulations can directly predict the Raman spectrum but are limited to small
      metal clusters and therefore are often used for understanding the CM. Thus, there
      is a need for developing new methods that bridge the electrodynamics simulations
      of the metal nanoparticle and the first-principles simulations of the molecule to
      facilitate direct simulations of SERS spectra. In this Account, we discuss our
      recent work on developing a hybrid atomistic electrodynamics-quantum mechanical
      approach to simulate SERS. This hybrid method is called the discrete interaction
      model/quantum mechanics (DIM/QM) method and consists of an atomistic
      electrodynamics model of the metal nanoparticle and a time-dependent density
      functional theory (TDDFT) description of the molecule. In contrast to most
      previous work, the DIM/QM method enables us to retain a detailed atomistic
      structure of the nanoparticle and provides a natural bridge between the
      electronic structure methods and the macroscopic electrodynamics description.
      Using the DIM/QM method, we have examined in detail the importance of the local
      environment on molecular excitation energies, enhanced molecular absorption, and
      SERS. Our results show that the molecular properties are strongly dependent not
      only on the distance of the molecule from the metal nanoparticle but also on its
      orientation relative to the nanoparticle and the specific local environment.
      Using DIM/QM to simulate SERS, we show that there is a significant dependence on
      the adsorption site. Furthermore, we present a detailed comparison between
      enhancements obtained from DIM/QM simulations and those from classical
      electrodynamics simulations of the local field. While we find qualitative
      agreement, there are significant differences due to the neglect of specific
      molecule-metal interactions in the classical electrodynamics simulations. Our
      results highlight the importance of explicitly considering the specific local
      environment in simulations of molecule-plasmon coupling. 

PMID- 23965412
TI  - The effect of low dose lipopolysaccharide on thyroid hormone-regulated actin
      cytoskeleton modulation and type 2 iodothyronine deiodinase activity in
      astrocytes.
AB  - Systemic infection/inflammation can severely interfere with brain development.
      Lipopolysaccharide (LPS) is a major cell wall component of gram-negative bacteria
      and commonly used to model the response by infections. Since perinatal exposure
      to LPS shows neurodevelopmental defects partly similar to those seen in perinatal
      hypothyroidism, we examined the effect of LPS on thyroxin (T4)-mediated
      signalings in astrocytes. Initially, C6 rat glioma-derived clonal cells were
      used, whose biological nature is similar to that of astrocytes. To measure the
      effects of LPS and T4, actin polymerization and D2 activity assays were carried
      out. LPS treatment (10 ng/mL) markedly induced actin depolymerization, whereas 10
      nM T4 promoted actin polymerization. Furthermore, T4 partly rescued LPS-induced
      actin depolymerization. LPS treatment (10 ng/mL) increased D2 activity, whereas
      T4 (10 nM) suppressed this activity. T4 restored LPS-increased D2 activity at 10
      nM. LPS-induced actin depolymerization and D2 activity were blocked by p38 MAP
      kinase inhibitor. Such effects were not seen in T4-mediated changes. Furthermore,
      similar results were found in the cerebellar primary astrocyte. These results
      indicate that, although LPS affects T4-regulated cellular events such as actin
      polymerization and D2 activity, which may induce neurodevelopmental defects
      similar to those in perinatal hypothyroidism, LPS signaling pathways are
      independent of T4 signaling pathways. 

PMID- 23965414
TI  - Atypical cutaneous vasculitis under lapatinib.

PMID- 23965415
TI  - Prescription.

PMID- 23965413
TI  - An evolving new paradigm: endothelial cells--conditional innate immune cells.
AB  - Endothelial cells (ECs) are a heterogeneous population that fulfills many
      physiological processes. ECs also actively participate in both innate and
      adaptive immune responses. ECs are one of the first cell types to detect foreign
      pathogens and endogenous metabolite-related danger signals in the bloodstream, in
      which ECs function as danger signal sensors. Treatment with lipopolysaccharide
      activates ECs, causing the production of pro-inflammatory cytokines and
      chemokines, which amplify the immune response by recruiting immune cells. Thus,
      ECs function as immune/inflammation effectors and immune cell mobilizers. ECs
      also induce cytokine production by immune cells, in which ECs function as immune
      regulators either by activating or suppressing immune cell function. In addition,
      under certain conditions, ECs can serve as antigen presenting cells (antigen
      presenters) by expressing both MHC I and II molecules and presenting endothelial
      antigens to T cells. These facts along with the new concept of endothelial
      plasticity suggest that ECs are dynamic cells that respond to extracellular
      environmental changes and play a meaningful role in immune system function. Based
      on these novel EC functions, we propose a new paradigm that ECs are conditional
      innate immune cells. This paradigm provides a novel insight into the functions of
      ECs in inflammatory/immune pathologies. 

PMID- 23965416
TI  - Emerging evidence for androgen replacement therapy in aging men.
AB  - The age-related changes in organ and system function of an individual increase
      the risk of developing certain diseases. The data presented in this article
      reviews current literature on the specific physiological effects of androgen
      deficiency in disease states and the risks and benefits of testosterone
      replacement therapy specifically in the areas of urologic, cardiac, and endocrine
      health. 

PMID- 23965417
TI  - Hormonal influences in prostate cancer: an update of a complex subject.
AB  - Pharmacists who are involved with patients and physicians have a tremendous
      opportunity to serve in the realm of prostate cancer, and there are numerous
      compounding opportunities. For example, compounded testosterone gels can help
      keep testosterone levels in the mid to upper range with proper dosing and patient
      counseling. Also, estradiol levels can be held in check or lowered by compounding
      aromatase-inhibitors such as anastrazole or letrazole into the lower doses that
      men require, rather than their more potent versions for female patients.
      Nutraceuticals such as omega-3 fatty acids, vitamin D, zinc, and selenium all
      play an important role in prostate health, as these agents have 5a-reductase
      inhibiting and anti-inflammatory properties. More than anything else, we see that
      the pathophysiology of prostate cancer, although quite complex, is being explored
      at an amazing rate. The author believes that hormonal balance is critical, and
      that it is largely hormonal imbalance that is involved in prostate disease. In
      that regard, the author concludes that the levels of testosterone, estradiol, and
      drotestosterone, experienced at a more youthful age are vital if we are to
      improve prostate health. 

PMID- 23965418
TI  - Determining the Causes of Erectile Dysfunction: Can Medications be a Double-Sided
      Sword?
AB  - Like other medical problems, diagnosing the causes of erectile dysfunction
      requires a series of tests, as well as trial and error. The possibility that side
      effects to a patient's medications may be one of the causes of erectile
      dysfunction is discussed often in published articles. Physicians are aware that
      in order to diagnose a physiological problem, the simplest causes for the problem
      should be considered and eliminated first. Therefore, the physician should review
      a patient's list of medications as first protocol. This article lists some of the
      more common causes of erectile dysfunction and provides a list of drugs that are
      linked to erectile dysfunction. Compounding pharmacists should be involved in the
      treatment of this physiological/psychological condition to offer private
      consultations and alternative medications to those patients who can't or
      shouldn't take certain manufactured drugs that may cause erectile dysfunction or,
      because of certain risks, drugs that are sold to treat erectile dysfunction. 

PMID- 23965419
TI  - Coenzyme q(10) supplementation in the treatment of heart disease.
AB  - Significant deficiencies in coenzyme Q(10) have been documented in a wide variety
      of diseases in both animal and human studies. Known predominately for its
      functions as an antioxidant and membrane stabilizer, coenzyme Q(10)
      supplementation also has been demonstrated to effectively lower blood pressure,
      decrease total cholesterol and low-density lipoprotein cholesterol, increase
      levels of high-density lipoprotein cholesterol, and decrease symptoms of dyspnea,
      peripheral edema, enlarged liver, and insomnia. The majority of clinical work
      with coenzyme Q(10) in the past two decades has focused on its role in heart
      disease. While usually found in high concentrations in heart muscle cells, both
      serum and tissue levels of coenzyme Q(10) are often lower in people with
      congestive heart failure. The severity of coenzyme Q(10) deficiency is directly
      related to the severity of heart failure. Correcting deficits in coenzyme Q(10)
      in heart failure patients can mitigate or reverse myocardial dysfunction and
      necrosis. The addition of coenzyme Q(10) to conventional treatments in congestive
      heart failure patients has been shown to improve quality of life and decrease
      hospitalization rates. In an effort to improve outcomes in patients supplemented
      with coenzyme Q(10), various delivery mechanisms to improve the bioavailability
      of coenzyme Q(10) are currently under investigation. 

PMID- 23965420
TI  - Case report: the use of inhaled cyclosprine to treat bronchiolitis obliterans
      syndrome in a lung transplant patient.
AB  - The first lung transplantation was performed successfully in 1983 and has become
      a viable option for end-stage pulmonary disease. Advances in surgical techniques,
      the development of better immunosuppressive agents, and the standardization of
      care have improved patient survival and quality of life. This article includes
      statistics on men versus women diagnosed with Chronic Obstructive Pulmonary
      Disease. Included with this article is a case report of a 52-year-old white male
      who had undergone a bilateral lung transplant. The patient's medication protocol
      is discussed within this article, including the use of inhaled cyclosporine to
      treat acute cellular rejection, one of the major complications associated with
      lung transplantation. The formulation for the cyclosporine for aerosol that was
      prepared by a compounding pharmacist is included with this article. 

PMID- 23965421
TI  - Developing a tretinoin oral liquid for patients who cannot take capsules.
AB  - Published information on alternative ways to administer commercial dosage forms
      may not always be the best option for patients and the hospital staff. There are
      resources available to research information about drugs and excipients. A
      compounding pharmacist can review the information and, based on training and
      experience in compounding, develop a formulation to meet the individual needs of
      a patient. The tretinoin oral suspension formulation included with this article
      is an example of how to develop a formulation without a published stability study
      by utilizing various compounding references and databases. 

PMID- 23965422
TI  - Inventory information approval system certification and flexible spending account
      purchases.
AB  - There is no question that 2009 was a year of change within the pharmacy industry.
      Several new requirements were implemented, including the need for an Inventory
      Information Approval System for accepting flexible spending or health
      reimbursement account cords. Some pharmacies relied on the 90% exemption rule,
      which is discussed within this article, or an alternative method to avoid the
      expense of a point of sale. However, with flexible spending or health
      reimbursement account card participation expected to reach 85% in 2010, now bay
      be the time for compounding pharmacists to weigh the pros and cons of Inventory
      Information Approval System certification. 

PMID- 23965423
TI  - Cop's Best Friend: Preventing the Illegal Distribution and Transportation of
      Prescription Drugs.
AB  - Law enforcement and the military have long relied on canines to provide
      protection of the handler and others involved in combating crime. One of the
      extremely important uses of canines is in the detection of illegal drugs, bombs,
      and other explosives to protect the President of the United States, other
      dignitaries, and the general public. This article discusses the details on a
      canine that was trained to detect major illicit pharmaceuticals. The efforts of
      this program were made easier with the help of a compounding pharmacist who
      willingly assisted the Warren County Drug Task Force in the Canine's detection
      training by preparing and individually labeling capsules that contained pure
      drug. Both parties share their experiences in this important endeavor to combat
      the illegal distribution and transportation of prescription drugs. 

PMID- 23965424
TI  - Owning an In-Network Pharmacy and a Second Out-of-Network Pharmacy that Performs
      Compounding: Suggestions on How to Avoid Being Terminated from the Pharmacy
      Benefits Manager Network.

PMID- 23965425
TI  - Quality-control: from record keeping to key performance indicators: manging
      quality in compounding pharmacies.
AB  - Record keeping is fundamental in any quality-management system. Compounding
      pharmacies use a quality-management system that is based on the Good Compounding
      Practices, which emphasizes the necessity and therefore the importance of
      maintaining records. However, the activity of recording without conducting
      further data analysis does not assure continuous improvement of the preparations,
      services, and of the system itself. The purpose of this article is to suggest
      some nonfinancial key performance indicators that can be easily implemented by
      compounding pharmacies to assist in the development of an organizational
      procedure for measuring the quality of products and services. This is a new
      paradigm for managing quality in compounding pharmacies. 

PMID- 23965426
TI  - Basics of compounding: considerations for implementing United States pharmacopeia
      chapter 797 pharmaceutical compounding-sterile preparations, part 18:
      verification of automated compounding devices for parenteral nutrition
      compounding and finished preparation release checks and tests.
AB  - A sound quality-assurance program, which should include standard operating
      procedures, documentation, verification, and analytical and microbiological
      testing, is necessary to ensure the quality of compounded preparations. This
      article discusses in a practical matter verification of automated compounding
      devices for parenteral nutrition compounding and finished preparation release
      checks and tests, and provides practice clarification to the standards set forth
      by the United States Pharmacopeial Convention, Inc. 

PMID- 23965427
TI  - Chemical stability of hydromorphone hydrochloride in patient-controlled analgesia
      injector.
AB  - The chemical stability of hydromorphone hydrochloride in patient-controlled
      analgesia injectors was studied for 34 weeks at different temperatures. The
      sterility of the solution was also monitored at the end of 16-week storage. For
      the determination of stability of hydromorphone, five groups of six patient
      controlled analgesia injectors containing hydromorphone solutions of 0.2 mg/mL (6
      mg of drug solution in 30 mL 0.9% normal saline) sealed with plastic tip caps
      were stored at 5 degrees Celsius in refrigerator, 20 degrees Celsius on bench
      top, 20 degrees Celsius in dark, 35 degrees Celsius in dark, and 50 degrees
      Celsius in dark. Chemical stability was determined throughout a storage period of
      34 weeks using high performance liquid chromatography. Sterility test was also
      performed at 16 weeks. Hydromorphone solutions stored in different conditions up
      to 34 weeks remained clear and free of visible precipitation throughout the
      study. After 8 weeks of storage in the patient-controlled analgesia injectors in
      different temperature conditions, the concentrations of hydromorphone in all the
      samples remained over 95% of their original value. At 16 and 34 weeks, the
      concentration of hydromorphone in the injectors decreased to 92% to 96% and 86%
      to 88% of their original value, respectively. In the sterility test of bacterial
      contamination of the hydromorphone solutions in the patient-controlled analgesia
      injectors at 16 weeks, none of the injector solutions showed evidence of
      microbial growth after 14 days of incubation in fluid thioglycolate medium. This
      study demonstrates the stability and sterility of hydromorphone hydrochloride
      solution. 

PMID- 23965428
TI  - Menopausal Women's Access Path to Bioidentical Hormone Replacement Therapy: An
      Exploratory.
AB  - The objective of this exploratory qualitative study was to describe (1) the key
      factors affecting women's initial decision to explore the use of bioidentical
      hormone, (2) where women gather their information on bioidentical hormones, (3)
      the enablers and barriers to obtaining bioidentical hormones, and (4) how to
      improve the bioidentical hormone replacement therapy access path. The study was
      conducted in a compounding pharmacy located in a large urban area in southern
      Ontario, Canada. The participants included four postmenopausal women between the
      ages of 46 and 72 who self-identified as users of bioidentical hormone
      replacement therapy and with comprehensive provincial healthcare coverage.
      Participants were recruited at a compounding pharmacy with the use of tri-fold
      brochures, tear-sheets, and posters. The women participated in an audio-taped
      mini focus group. Discussion was guided by six open-ended questions. Verbatim
      quotes were analyzed using an affinity diagram. Participants identified three key
      factors related to their initial decision: (1) symptoms unalleviated by synthetic
      hormone replacement therapy, (2) side effects from synthetic hormone replacement
      therapy, and (3) personal preference. They obtained information and support from
      many sources, including: family/friends, publications, and specialists in
      menopausal health. Once participants had made a decision, they obtained a
      prescription and accessed bioidentical hormone replacement therapy at a
      compounding pharmacy. Knowledgeable primary care physicians and compounding
      pharmacists were seen as enablers. Lack of support/Information and costs were
      identifies as barriers. Improvements to bioidentical hormone replacement therapy
      access path were suggested. The results of this study suggest that there may be
      value in implementing strategies to further encourage family physicians and other
      specialists in menopausal health to discuss options regarding hormone replacement
      therapy with patients. For example, the preparation and distribution of updated
      consumer decision aids that summarize the evidence on the options regarding
      hormone replacement therapy, including bioidentical hormone replacement therapy,
      could be considered. 

PMID- 23965429
TI  - Low dose naltrexone: side effects and efficacy in gastrointestinal disorders.
AB  - Use of low dose naltrexone has been advocated for a variety of medical problems.
      Only a few articles published in peer review journals have documented side
      effects of low dose naltrexone. The purpose of this study was to determine the
      frequency of adverse effects of low dose naltrexone in patients who have been
      treated for a variety of gastrointestinal disorders. The secondary purpose was to
      determine global efficacy in a retrospective survey. Patients (206) form a single
      gastroenterologist's clinical practice who had been prescribed naltrexone were
      mailed a survey to evaluate the side effects and efficacy of naltrexone. Patients
      had either irritable bowel syndrome without evidence for small intestinal
      bacterial overgrowth, chronic idiopathic constipation, or inflammatory bowel
      disease. Patients with diarrhea were given 2.5 mg daily, constipation 2.5 mg
      twice daily, and inflammatory bowel disease 4.5 mg daily. In the patients who
      returned the survey, 47/121 (38.8%) had no side effects. Of the 74/121 (61.2%)
      patients who had side effects, 58 had one or more neurological complaints, and 32
      had one or more gastrointestinal side effects. In the patients with side effects,
      24/74 (32.4%) had short lived symptoms. Low dose naltrexone was terminated owing
      to side effects in 20/74 patients (27.0%). In 13 patients with idiopathic
      irritable bowel syndrome, 2 were markedly worse. In 85 patients with irritable
      bowel syndrome-small intestinal bacterial overgrowth, 15 were markedly improved,
      32 were moderately worse, and 1 was markedly worse. In 12 patients with chronic
      constipation, 7 were markedly improved, 1 was moderately improved, 1 was mildly
      improved, and 4 were unchanged. Low dose naltrexone frequently has side effects
      but in most is tolerable. It appears to be helpful for a member of patients with
      gastrointestinal disorders. 

PMID- 23965430
TI  - Earthworm-derived pore-forming toxin lysenin and screening of its inhibitors.
AB  - Lysenin is a pore-forming toxin from the coelomic fluid of earthworm Eisenia
      foetida. This protein specifically binds to sphingomyelin and induces erythrocyte
      lysis. Lysenin consists of 297 amino acids with a molecular weight of 41 kDa. We
      screened for cellular signal transduction inhibitors of low molecular weight from
      microorganisms and plants. The purpose of the screening was to study the
      mechanism of diseases using the obtained inhibitors and to develop new
      chemotherapeutic agents acting in the new mechanism. Therefore, our aim was to
      screen for inhibitors of Lysenin-induced hemolysis from plant extracts and
      microbial culture filtrates. As a result, we isolated all-E-lutein from an
      extract of Dalbergia latifolia leaves. All-E-lutein is likely to inhibit the
      process of Lysenin-membrane binding and/or oligomer formation rather than pore
      formation. Additionally, we isolated tyrosylproline anhydride from the culture
      filtrate of Streptomyces as an inhibitor of Lysenin-induced hemolysis. 

PMID- 23965431
TI  - Effects of decreased vitamin D and accumulated uremic toxin on human CYP3A4
      activity in patients with end-stage renal disease.
AB  - In patients with end-stage renal disease, not only renal clearance but also
      hepatic clearance is known to be impaired. For instance, the concentration of
      erythromycin, a substrate of cytochrome P450 3A4 (CYP3A4), has been reported to
      be elevated in patients with end-stage renal disease. The purpose of this study
      is to elucidate the reason for the decrease in hepatic clearance in patients with
      end-stage renal disease. Deproteinized pooled sera were used to assess the
      effects of low-molecular-weight uremic toxins on CYP3A4 activity in human liver
      microsomes and human LS180 cells. Four uremic toxins (3-carboxy-4-methyl-5-propyl
      2-furanpropanoic acid, hippuric acid, indole-3-acetic acid, and 3-indoxyl
      sulfate) present at high concentrations in uremic serum were also studied.
      Simultaneous treatment of uremic serum (less than 10%) or uremic toxins did not
      affect testosterone 6beta-hydroxylation in human liver microsomes. On the other
      hand, pretreatment of each serum activates CYP3A4 in LS180 cells, and the
      increased CYP3A4 activity in uremic serum-treated cells was smaller than normal
      serum-treated cells. In addition, CYP3A4 and CYP24A1 mRNA levels also increased
      in LS180 cells exposed to normal serum, and this effect was reduced in uremic
      serum-treated cells and in cells exposed to uremic serum added to normal serum.
      Furthermore, addition of 1,25-dihydroxyvitamin D to uremic serum partially
      restored the serum effect on CYP3A4 expression. The present study suggests that
      the decrease of 1,25-dihydroxyvitamin D and the accumulation of uremic toxins
      contributed to the decreased hepatic clearance of CYP3A4 substrates in patients
      with end-stage renal disease. 

PMID- 23965433
TI  - The development of a sensitive methodology to characterise hard shell capsule
      puncture by dry powder inhaler pins.
AB  - In order for hard-shell capsules to function effectively as drug reservoirs in
      dry powder inhalers, the capsule must be punctured with sharpened pins to release
      the powdered medicament upon inspiration. Capsule performance in this setting is
      poorly understood. This study aims to develop a methodology to characterise hard
      shell capsule penetration by needles from commercial dry powder inhalers, to
      determine whether changes to capsule materials impact on their performance. Two
      pin types from two commercial dry powder inhalers were mounted in a material
      testing machine, equipped with a 500 N load cell. A stainless steel bush was used
      to secure a capsule directly below the steel pin. Hypromellose (n=10) and gelatin
      capsules (n=10) were conditioned in 'normal' or low humidity conditions and were
      subsequently punctured with both types of pin. Each puncture event was recorded
      on a load-displacement curve. The force required for puncture was 2.82+/-0.26 N
      for hypromellose capsules and 4.54+/-0.26 N for gelatin capsules, stored in
      normal humidity. Different capsule materials possessed distinguishable signature
      profiles but repeated force-displacement profiles were highly reproducible i.e.
      intra-individual variability was minimal. A rapid, robust yet sensitive
      methodology has therefore been developed that is able to characterise hard shell
      capsule materials based on the puncture performance.

PMID- 23965432
TI  - Immunotoxins: the role of the toxin.
AB  - Immunotoxins are antibody-toxin bifunctional molecules that rely on intracellular
      toxin action to kill target cells. Target specificity is determined via the
      binding attributes of the chosen antibody. Mostly, but not exclusively,
      immunotoxins are purpose-built to kill cancer cells as part of novel treatment
      approaches. Other applications for immunotoxins include immune regulation and the
      treatment of viral or parasitic diseases. Here we discuss the utility of protein
      toxins, of both bacterial and plant origin, joined to antibodies for targeting
      cancer cells. Finally, while clinical goals are focused on the development of
      novel cancer treatments, much has been learned about toxin action and
      intracellular pathways. Thus toxins are considered both medicines for treating
      human disease and probes of cellular function. 

PMID- 23965434
TI  - Lecithin-based emulsions for potential use as saliva substitutes in patients with
      xerostomia--viscoelastic properties.
AB  - The purpose of the present study was to investigate lecithin-rice bran oil
      rheological properties with the view to consider these as potential saliva
      substitutes in patients with severe xerostomia and salivary hypofunction. Pseudo
      ternary phase diagrams of rice bran oil, lecithin and water mixtures were
      constructed and characterised using polarising light microscopy. Viscoelastic
      properties, which we hypothesise are important determinants in product
      performance, were analysed using both flow and oscillatory rheology. Rheological
      properties were influenced by composition, frequency and shear stress. Frequency
      dependent viscoelasticity was observed in some formulations where viscosity
      dominated (tandelta>1) at frequencies under 5 Hz and elasticity dominated
      (tandelta<1) at higher frequencies. Threshold frequencies were determined for
      each formulation, where a peak in loss tangent was observed, coinciding with a
      reduction in the storage modulus and increase in loss modulus. The frequency
      dependent behaviour of emulsions are of interest because these combinations
      exhibit viscous behaviour at low frequencies, which may improve lubrication of
      the oral cavity at rest, whereas increased elasticity at higher frequencies may
      improve retention during higher-shear tasks such as swallowing and speaking.

PMID- 23965435
TI  - Serogroup W135 meningococcal disease, The Gambia, 2012.
AB  - In 2012, an outbreak of Neisseria meningitidis serogroup W135 occurred in The
      Gambia. The attack rate was highest among young children. The associated risk
      factors were male sex, contact with meningitis patients, and difficult breathing.
      Enhanced surveillance facilitates early epidemic detection, and multiserogroup
      conjugate vaccine could reduce meningococcal epidemics in The Gambia. 

PMID- 23965436
TI  - Graphene nanonet for biological sensing applications.
AB  - We report a simple but efficient method to fabricate versatile graphene nanonet
      (GNN)-devices. In this method, networks of V2O5 nanowires (NWs) were prepared in
      specific regions of single-layer graphene, and the graphene layer was selectively
      etched via a reactive ion etching method using the V2O5 NWs as a shadow mask. The
      process allowed us to prepare large scale patterns of GNN structures which were
      comprised of continuous networks of graphene nanoribbons (GNRs) with chemical
      functional groups on their edges. The GNN can be easily functionalized with
      biomolecules for fluorescent biochip applications. Furthermore, electrical
      channels based on GNN exhibited a rather high mobility and low noise compared
      with other network structures based on nanostructures such as carbon nanotubes,
      which was attributed to the continuous connection of nanoribbons in GNN
      structures. As a proof of concept, we built DNA sensors based on GNN channels and
      demonstrated the selective detection of DNA. Since our method allows us to
      prepare high-performance networks of GNRs over a large surface area, it should
      open up various practical biosensing applications. 

PMID- 23965437
TI  - Antibiotic stewardship among dentists: the need of the hour!!!!!!

PMID- 23965438
TI  - Characterization of salivary protein during ovulatory phase of menstrual cycle
      through MALDI-TOF/MS.
AB  - CONTEXT: Predicting ovulation is the basis on which the fertile period is
      determined. Nowadays there are many methods available to detect the ovulatory
      period. Unfortunately, these methods are not always effective for accurate
      detection of ovulation. Hence, an attempt was made to detect ovulation through
      single dimension sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS
      PAGE) analysis of protein with the help of saliva ferning. AIMS: The aim of this
      study was to determine the association of protein level with endogenous
      reproductive hormone level across the menstrual cycle. SETTINGS AND DESIGN:
      Salivary protein and its confirmation were evaluated during menstrual cycle
      followed by SDS-PAGE and Mass spectrometry. STATISTICAL METHOD USED: The protein
      content present in saliva throughout menstrual cycle is trail by SPSS statistical
      software version. MATERIALS AND METHODS: Salivary proteins were investigated
      serially during pre-ovulatory, ovulatory and post-ovulatory periods of normal
      menstrual cycle in eighteen healthy volunteers. The samples were collected in
      three consecutive menstrual cycles. Salivary protein was estimated and analyzed
      by single dimension SDS-PAGE. RESULTS: The results revealed significant
      variations in protein concentrations during the menstrual cycle. Protein levels
      were maximum during ovulation and minimum during postovulatory phase. Further,
      single dimension SDS-PAGE analysis showed seven different fractions of proteins
      is from 14-90 kilo Dalton (kDa) in the three phases of the menstrual cycle.
      CONCLUSIONS: Among the proteins, 48 kDa protein was more predominantly exhibited
      during ovulatory phase than pre and post-ovulatory phase. The present study
      indicates that the protein level and the specific protein band (48 kDa) through
      MALDI-TOF MS analysis might serve as an indicator for ovulation.

PMID- 23965439
TI  - Evaluation of total antioxidant capacity of saliva and serum in caries-free and
      caries-active adults: an in-vivo study.
AB  - CONTEXT: Oxidative stress is defined as an imbalance between the production of
      reactive oxygen species and antioxidant defense systems which are widely
      recognized as an important feature of many diseases including dental caries,
      suggesting that total antioxidant status may be of importance in determining the
      progression of caries. AIM: The aim of this study was to estimate the total
      antioxidant capacity (TAC) in saliva and serum of caries-free and caries-active
      adults and to correlate the TAC level with DMFT index (D = decayed, M = missing,
      F = filled, T = teeth). SETTINGS AND DESIGN: The present study included 100
      healthy adults who were divided into four groups: Control, group I, group II, and
      group III, with a DMFT index 0, <3, <10, and >10, respectively. MATERIALS AND
      METHODS: Saliva and serum samples were collected from all the four groups. The
      TAC of saliva and serum was estimated by phosphomolybdenum method. STATISTICAL
      ANALYSIS USED: One-way analysis of variance (ANOVA) was used to compare the TAC
      of saliva and serum. Only differences with "P" < 0.05 were considered
      statistically significant. RESULTS: The mean TAC level of both saliva and serum
      increased significantly (P < 0.001) with the DMFT index. CONCLUSION: Total
      antioxidant capacity of saliva has a linear relation with caries, i.e., as the
      severity of caries increases, the TAC level also increases.

PMID- 23965441
TI  - Color stability and flexural strength of poly (methyl methacrylate) and bis
      acrylic composite based provisional crown and bridge auto-polymerizing resins
      exposed to beverages and food dye: an in vitro study.
AB  - AIM: To evaluate the color stability and flexural strength of poly (methyl
      methacrylate) (PMMA) and bis-acrylic composite based provisional crown and bridge
      auto-polymerizing resins exposed to tea, coffee, cola, and food dye. MATERIALS
      AND METHODS: Two provisional crown and bridge resins, one DPI self-cure tooth
      molding powder (PMMA) (Group A), and one Protemp 4 Temporization Material (bis
      acrylic composite) (Group B) were used. Disk-shaped specimens for color stability
      testing (n = 30 for each material) and bar-shaped specimens for flexural strength
      testing (n = 30 for each material) were fabricated using a metal mold. The
      specimens were immersed in artificial saliva, artificial saliva + tea, artificial
      saliva + coffee, artificial saliva + cola, and artificial saliva + food dye
      solutions and stored in an incubator at 37 degrees C. Color measurements were
      taken before immersion, and then after 3 and 7 days of immersion. Flexural
      strength was evaluated after 7 days of immersion. RESULTS: Group A showed
      significantly higher color stability as compared to Group B, and artificial
      saliva + coffee solution had the most staining capacity for the resins. Test
      solutions had no effect on the flexural strength of Group A, but Group B
      specimens immersed in artificial saliva + cola showed significantly lower
      flexural strength values as compared to the control group. CONCLUSION: The
      findings of the study showed that for materials used in the study, PMMA was more
      color stable than bis-acrylic composite based resin. Also, material based on PMMA
      was more resistant to damage from dietary beverages as compared to bis-acrylic
      composite based provisional crown and bridge resin.

PMID- 23965440
TI  - Immunohistochemical analysis of CK 18 in dental follicles of impacted third
      molars: a pilot study.
AB  - OBJECTIVE: Odontogenic tumors are lesions derived from epithelial,
      ectomesenchymal, and/or mesenchymal elements that still are, or have been, part
      of the tooth-forming apparatus. Approximately 80% of odontogenic tumors occur in
      the mandible, with a marked predilection for the posterior region, and are often
      associated with an unerupted tooth. The aim of this study was to determine
      whether cytokeratin (CK) 18 immunostaining decorated the follicular tissue
      removed at the time of prophylactic extraction of impacted mandibular third
      molars, which might suggest oncofetal transformation. MATERIALS AND METHODS:
      Fifty-four impactions met the study inclusion criteria, of which 24 cases showed
      the presence of reduced enamel epithelium and/or connective tissue with
      odontogenic epithelium, which were subjected to CK 18 immunostaining. RESULTS:
      All 24 cases with adequate epithelium were CK 18 immunonegative. CONCLUSION:
      There was no oncofetal transformation in the odontogenic epithelia of the dental
      follicles studied. Thus, although we reaffirm that evaluation of follicular
      tissue is imperative since disease conditions may be found in minute follicular
      spaces, development of odontogenic cysts and tumors is unlikely.

PMID- 23965442
TI  - Connector design in a long-span-fixed dental prosthesis: a three-dimensional
      finite element analysis.
AB  - OBJECTIVES: The goal of every prosthetic management is to simulate nature and be
      in harmony with nature within the physiological limits. The occlusal forces on a
      fixed dental prosthesis are transmitted to the surrounding structures through
      pontics, connectors and retainers and more stresses are seen at the connector
      region. To analyze the stress patterns in cast and soldered connectors between
      the two pontics and between the retainer and pontic of a four unit fixed dental
      prosthesis on axial and non axial loading and also to observe and ascertain the
      need to modify the design of the rigid connectors. MATERIALS AND METHODS:
      Subsequently four models each of cast and soldered connectors with cylindrical
      and triangular design, of dimension 3 * 4 mm and thickness 0.5 mm was designed
      for the study. The first premolar and second molar were considered as the
      abutments and 2 nd premolar and 1 st molar as the pontics. The analysis was done
      using ANSYS version 8.0 software and by placing axial and non-axial load of 40
      Newtons each. RESULTS: Von Misses stresses were observed at the connector region
      between the two pontics, especially in the cervical region. CONCLUSION: The
      cylindrical cast connectors showed less stress in comparison to triangular design
      and the difference in the stress distribution of cast and soldered connectors
      were marginal. CLINICAL SIGNIFICANCE: The occlusal forces on a fixed dental
      prosthesis are transmitted to the surrounding structures through pontics,
      connectors and retainers with maximum stresses concentrated at the connectors.
      Hence this three-dimensional finite element analysis study investigated stress
      distribution in a four unit posterior fixed dental prosthesis, having cylindrical
      and triangular connector designs.

PMID- 23965444
TI  - Evaluation and comparison of interleukin-8 (IL-8) level in gingival crevicular
      fluid in health and severity of periodontal disease: a clinico-biochemical study.
AB  - BACKGROUND: Cytokines play an important role in the pathology associated with
      chronic inflammatory diseases. Because of pro-inflammatory and neutrophil
      chemotactic properties, the cytokines like interleukins (IL) may play a
      significant role in the pathogenesis of periodontitis. The biological effects of
      IL-8 are relevant in this regard. AIM: This study was done to compare the level
      of this molecule in gingival crevicular fluid (GCF) from patients with adult
      periodontitis (experimental group) and from individuals with clinically healthy
      gingival (control group). MATERIALS AND METHODS: GCF was collected from patients
      with adult periodontitis and clinically healthy gingival for 30 s using a
      Periopaper strip and the volume of the sample determined. Following elution of
      the fluid, assays for IL-8 were carried out by enzyme-linked immunosorbent assay
      (ELISA). The concentration of IL-8 was calculated in the original volume of GCF
      on each strip. RESULTS: The level of IL-8 in the experimental group was
      significantly higher than in the control group ( P < 0.01). The clinical
      parameters were positively correlated to IL-8, suggesting that the GCF IL-8
      exhibited dynamic changes upon severity of periodontal disease ( P < 0.05).
      CONCLUSION: These data suggest that level of IL-8 is associated with periodontal
      status. The level of IL-8 in GCF is valuable in detecting the inflammation of
      periodontal tissue.

PMID- 23965443
TI  - Incidence of cystic changes in impacted lower third molar.
AB  - OBJECTIVE: To assess the incidence of cystic changes in the impacted lower third
      molar (ILTM) in which the pericoronal (follicular) space is less than 2.5 mm as
      measured from the radiograph. The relationship between the cystic changes and
      patient's age, sex, and angular position and contact of ILTM with adjacent tooth
      was also evaluated. MATERIALS AND METHODS: Follicular space less than 2.5 mm as
      measured from the panoramic radiograph was included in the study. A total of 73
      tissue samples collected during the extraction ILTM were examined
      histopathologically. Then the data were analyzed for associations with age, sex,
      angular position, and contact of the ILTM with an adjacent tooth. RESULTS: There
      were 37 male and 36 female patients, age ranging from 17 to 35 years (mean 23.95
      years). Out of 73 specimens, 17 (23.3%) showed cystic changes; among them 16
      (22.1%) showed dentigerous cysts and 1 (1.2%) showed odontogenic keratocysts.
      Most of the cystic changes occurred in the 26-30 year age range. The cystic
      changes showed male predominance but could not gain statistical significance. The
      relationship between cystic changes and angular position was statistically
      significant (P < 0.05). Higher probability was found in distoangular positioned
      ILTM. The relationship between cystic changes and communication of ILTM with the
      second molar was not statistically significant. CONCLUSION: Incidence of cystic
      changes in ILTM justifies extraction of the impacted tooth associated with
      symptoms. The decision to extract or not to extract impacted third molar should
      be individualized, rather than generalized.

PMID- 23965445
TI  - A comparative evaluation of fracture resistance of endodontically treated teeth,
      with variable marginal ridge thicknesses, restored with composite resin and
      composite resin reinforced with Ribbond: an in vitro study.
AB  - BACKGROUND: The anatomic shape of maxillary premolars show a tendency towards
      separation of their cusps during mastication after endodontic treatment.
      Preservation of the marginal ridge of endodontically treated and restored
      premolars can act as a strengthening factor and improve the fracture resistance.
      OBJECTIVES: To evaluate the effect of varying thickness of marginal ridge on the
      fracture resistance of endodontically treated maxillary premolars restored with
      composite and Ribbond reinforced composites. MATERIALS AND METHODS: One hundred
      and twenty, freshly extracted, non carious human mature maxillary premolars were
      selected for this experimental in vitro study. The teeth were randomly assigned
      in to twelve groups ( n = 10). Group 1 received no preparation. All the premolars
      in other groups were root canal treated. In subgroups of 3 and 4, DO cavities
      were prepared while MOD cavities were prepared for all subgroups of group 2, the
      dimensions of the proximal boxes were kept uniform. In group 3 and 4 the
      dimensions of the mesial marginal ridge were measured using a digital Vernier
      caliper as 2 mm, 1.5 mm, 1 mm and 0.5 mm in the respective subgroups. All samples
      in groups 2.2 and all the subgroups of 3 were restored with a dentin bonding
      agent and resin composite. The teeth in group 2.3 and all subgroups of 4 were
      restored with composite reinforced with Ribbond fibers. The premolars were
      submitted to axial compression up to failure at 45 degree angle to a palatal cusp
      in universal testing machine. The mean load necessary to fracture was recorded in
      Newtons and the data was analysed. RESULTS: There was a highly significant
      difference between mean values of force required to fracture teeth in group 1 and
      all subgroups of group 2, 3 and 4 (i.e., P < 0.01) CONCLUSION: On the basis of
      static loading, preserving the mesial marginal ridge with thicknesses of mm, 1.5
      mm, 1 mm and 0.5 mm, composite restored and Ribbond reinforced composite restored
      maxillary premolars can help preserve the fracture resistance of teeth.

PMID- 23965446
TI  - Prevalence and determinant of early childhood caries among the children attending
      the Anganwadis of Wardha district, India.
AB  - BACKGROUND: Dental caries is one of the most common chronic diseases of early
      childhood. Dental problems in early childhood have been shown to be predictive of
      future dental problems, growth and development by interfering with comfort,
      nutrition, concentration, and school participation. AIM: To find out the
      prevalence of Early childhood caries (ECC) among the children attending the
      Anganwadis of Wardha district, to determine the feeding habits and their
      relationship to early childhood caries. MATERIALS AND METHODS: Community-based
      cross-sectional study among the selected Anganwadis children of 2-5 years of
      Wardha district. RESULT: A total 330 subjects, 105 children were found to be
      having ECC, 47 (30.92%) males and 58 (32.58%) females. Total 215 children
      belonged to 43-60 months age group. Out of these, 72 (33.48%) children were
      having ECC. A significant association was found between the history of bottle
      feeding and ECC (P = 0.0218). Prevalence of ECC was more among those who were
      bottle-fed than those who were not bottle-fed. CONCLUSION: Future health
      promotion and education programs in Anganwadis should include oral health issues
      and the risk factors for ECC, and its consequences should be addressed. Public
      funded oral health program should be started and targeted at children from lower
      socioeconomic status. Effective strategies should be developed to promote use of
      brush and paste for cleaning teeth and discouraging inappropriate bottle-feeding,
      discouraging on demand consumption of chocolates and sugars.

PMID- 23965447
TI  - Topography of the pulp chamber in the maxillary primary molars of a Tunisian
      children.
AB  - BACKGROUND: Knowledge of the variations in pulp chamber topography is very useful
      to the dentist while performing endodontic access cavity in primary teeth. AIM:
      To determine the horizontal crown dimensions and the pulp chamber topography of
      shedding maxillary primary molars in a sample of Tunisian children. MATERIALS AND
      METHODS: Forty two maxillary primary molars (24 first and 18 second molars) were
      used. Teeth were ultrasonically cleaned before taking morphometric measurements
      of the buccolingual and mesiodistal sizes. Statistical student test was used
      comparing the mean sizes. RESULTS: All the crown measurements were higher in the
      second molar. While the buccolingual dimension of the pulp chamber was higher in
      the second molar, the mesiodistal sizes were equivalent among the teeth. The
      thickest walls were in the buccal side of the first molar and in the mesial side
      of the second one. The ratio of several measurements indicate that the pulp
      cavity is more vestibularly and distally located in the second molar. CONCLUSION:
      Mesiodistal dimension of the pulp cavity is not proportional to that of the
      dental crown. Endodontic access cavity have to be shifted to the distal and
      vestibular sides from the first to the second upper molar.

PMID- 23965448
TI  - Excision of oral mucocele by different wavelength lasers.
AB  - BACKGROUND: Mucocele is a common benign neoplasm of oral soft tissues and the
      most common after fibroma. It generally occurs in the lower lip and its treatment
      includes excision of cyst and the responsible salivary gland, in order to prevent
      recurrences. AIMS: To evaluate the capability of three different lasers in
      performing the excision of labial mucocele with two different techniques.
      MATERIALS AND METHODS: In the presented cases, excision was performed using two
      different techniques (circumferential incision technique and mucosal preservation
      technique) and three different laser wavelengths (Er,Cr:YSGG 2780 nm, diode 808
      nm, and KTP 532 nm). RESULTS: All the tested lasers, regardless of wavelength,
      showed many advantages (bloodless surgical field, no postoperative pain, relative
      speed, and easy execution). The most useful surgical technique depends on
      clinical features of the lesion. CONCLUSION: Tested lasers, with both techniques,
      are helpful in the management of labial mucocele.

PMID- 23965449
TI  - Evaluation of resistance form of different preparation features on mandibular
      molars.
AB  - AIMS: Resistance form of full metal-ceramic crown is an important feature that
      determines longevity of these restorations. This study evaluated the resistance
      form of full metal-ceramic prepared with four different design features.
      MATERIALS AND METHODS: An acrylic tooth was prepared with 20 degrees  total
      occlusal convergence (TOC) angle, 2.5 mm of occlusocervical dimension and a
      shoulder finishing line. This design lacked resistance form. The crown
      preparation was subsequently modified by preparing Mesial Occlusal Distal
      isthmus, placing occlusal inclined plane, and reducing TOC. Four metal dies from
      these designs were constructed by lathe machine and then 10 metal copings were
      fabricated for each preparation. Metal coping were cemented on metal dies with
      temp-bond cement. Force was applied at 45 degrees  from lingual to buccal
      direction with universal testing machine. STATISTICAL ANALYSIS USED: The data
      were evaluated by Kruskal-Wallis and non-parametric Mann-Whitney test. RESULTS:
      All features increased resistance form when compare to control group. However,
      reduce TOC group showed greatest value of resistance. CONCLUSION: Within the
      limitation of this study, reducing the tapering of occlusocervival dimension is
      the most effective way in increasing resistance form, although, other features
      were also effective.

PMID- 23965450
TI  - A 10-year retrospective study on odontogenic tumors in Iran.
AB  - OBJECTIVE: The aim of this study was to review cases of odontogenic tumors
      diagnosed in two pathology centers in Tehran, Iran, during a 10-year period.
      STUDY DESIGN: Patients' records were seen at two teaching pathology Centre's of
      Shahid Beheshti University between the months of March 2000 to 2010 with
      histologic diagnosis of any type of odontogenic tumors. The records were analyzed
      for frequency, age, sex, site, as well as clinical, radiographic and
      histopathologic findings. RESULTS: Of 30706 biopsies, 4767 (15.5%) cases were
      diagnosed as oral and maxillofacial lesions. Among these, 720 cases were tumoral
      with 188 (26.1%) cases of odontogenic tumors. Tumors with odontogenic epithelium
      origin formed 70.2% of total numbers of odontogenic tumors. Mixed odontogenic
      tumors and tumors of odontogenic ectomesenchyme comprised 12.2% and 17.5% of the
      cases respectively. Ameloblastoma, with a frequency of 62.2% was the most common
      tumor in this review which was followed by odontoma and odontogenic myxoma.
      CONCLUSION: Although there are few studies on odontogenic tumors in literature,
      the comparison of our results with existing data shows significant differences in
      the distribution of tumors and age of patients, which may be due to ethnic
      features and geographic distribution of patients. Future studies on other ethnic
      groups are essential for further clarification of the findings in this research.

PMID- 23965451
TI  - The effect of photoactivation time and light tip distance on the degree of
      conversion of light and dual-cured dentin adhesives.
AB  - BACKGROUND: The degree of conversion of dental adhesive is an important parameter
      since poor mechanical properties are related to low percentage of monomer-to
      polymer conversion within resin-based materials. OBJECTIVES: To evaluate the
      influence of polymerization time and light guide distance on the degree of
      conversion (DC) of three contemporary dental adhesives. MATERIALS AND METHODS:
      The spectral data of ExciTE DSC, Single Bond (r) , and Adper (r) Prompt L-Pop
      were analyzed using FTIR spectroscopy after 20 s, 40 s, and 60 s of
      photoactivation times. Light tip distances were kept at 1, 3, and 6 mm during the
      exposures. STATISTICS: Data were analyzed using ANOVA and Tukey's test (alpha =
      0.05). RESULTS: Within groups, greater DC values were found using a tip distance
      of 1 mm or a 60-s curing time for Single Bond (r) (59%) and Adper (r) Prompt L
      Pop (65%). No statistically significant difference (P > 0.05) was found using
      either 1 mm or 3 mm tip distances after 20 s, 40 s, and 60 s of light curing time
      for Single Bond (r) . ExciTE (r) DSC showed the greatest DC values with light tip
      distances of 1 mm (90%) and 3 mm (89%), using 60 s of light curing. CONCLUSION:
      The self-etch adhesive Adper (r) Prompt L-Pop could be applied in shallow cavity
      preparations and must be light cured for at least 40 s. The light-cured total
      etch adhesive ExciTE (r) DSC could be applied in every restorative scenario if
      the curing time is extended up to 60 s or if the tip distance is extended up to 3
      mm.

PMID- 23965452
TI  - A comparison between conventional and digital radiography in root canal working
      length determination.
AB  - AIM AND OBJECTIVES: Obtaining a correct working length is necessary for
      successful root canal treatment. The aim of this study was to compare
      conventional and digital radiography in measuring root canal working length.
      MATERIALS AND METHODS: In this in vitro study 20 mesio buccal canal from
      maxillary first molars with moderate and severe curvature and 20 canal form
      anterior teeth with mild curvature were chosen and their working length were
      measured with number 15 k file (Maillefer, DENTSPLY, Germany). Then for each
      canal five radiographies were taken, three conventional radiographies using three
      methods of processing: Manual, automatic, and monobath solution; in addition to
      two other digital radiographies using CCD and PSP receptors. Two independent
      observers measured working length in each technique. Finally, the mean of working
      length in each group was compared with real working length using a paired T-test.
      Also a one-way ANOVA test was used for comparing the two groups. The level of
      statistical significance was P < 0.05. RESULTS: The results have shown that there
      was a high interobserver agreement on the measurements of the working length in
      conventional and digital radiography (P <= 0.001). Also there was no significant
      difference between conventional and digital radiography in measuring working
      length (P > 0.05). CONCLUSION: Therefore it was concluded that the accuracy of
      digital radiography is comparable with conventional radiography in measuring
      working length, so considering the advantages of the digital radiography, it can
      be used for working length determination.

PMID- 23965453
TI  - Prevalence of two root canals in human mandibular anterior teeth in an Iranian
      population.
AB  - BACKGROUND: Complete debridement and obturation of the root canal system is a key
      factor in successful endodontic treatment and the operator should therefore have
      thorough knowledge of the root canal morphology of the teeth. Numerous studies
      have been carried out to investigate the canal configuration of different tooth
      types in various populations. AIMS: The aim of the present study was to
      investigate the internal anatomy of mandibular incisors and canines in an Iranian
      population. MATERIALS AND METHODS: A total of 463 mandibular anterior teeth,
      including 186 centrals, 128 laterals, and 149 canines, were examined. A standard
      clearing technique was used to make the teeth transparent. India ink was injected
      into the canals of the teeth and the samples were examined with a magnifying
      glass. The root canal configurations were categorized according to the Vertucci
      classification. RESULTS: All the incisors in this study had one root, and 12.08%
      of the canines had two roots. We found a slightly higher prevalence of the second
      canal in incisors than in canines (36.62% vs. 20.48%). However, the probability
      of canines having two separate apical foramina was higher than that for incisors
      (12.08% vs. 0.64%). CONCLUSIONS: In view of the high prevalence of two-canaled
      mandibular anterior teeth found in this study, it would be prudent to assume that
      any mandibular anterior tooth being treated is two-canaled until a thorough
      search proves otherwise.

PMID- 23965454
TI  - Effect of fiber diameter on flexural properties of fiber-reinforced composites.
AB  - BACKGROUND: Flexural strength (FS) is one of the most important properties of
      restorative dental materials which could be improved in fiber-reinforced
      composites (FRCs) by several methods including the incorporation of stronger
      reinforcing fibers. AIM: This study evaluates the influence of the glass fiber
      diameter on the FS and elastic modulus of FRCs at the same weight percentage.
      MATERIALS AND METHODS: A mixture of 2,2-bis-[4-(methacryloxypropoxy)-phenyl]
      propaneand triethyleneglycol dimethacrylate (60/40 by weight) was prepared as the
      matrix phase in which 0.5 wt. % camphorquinone and 0.5 wt. % N-N'
      dimethylaminoethyl methacrylate were dissolved as photoinitiator system. Glass
      fibers with three different diameters (14, 19, and 26 MUm) were impregnated with
      the matrix resin using a soft brush. The FRCs were inserted into a 2 * 2 * 25 mm3
      mold and cured using a light curing unit with an intensity of ca. 600 mW/cm2 .
      The FS of the FRCs was measured in a three-point bending method. The elastic
      modulus was determined from the slope of the initial linear part of stress-strain
      curve. The fracture surface of the composites was observed using scanning
      electron microscopy to study the fiber-matrix interface. STATISTICAL ANALYSIS:
      The results were analyzed and compared using one-way ANOVA and Tukey's post-hoc
      test. RESULTS: Although the FS increased as the diameter of fibers increased up
      to 19 MUm (P < 0.05), no significant difference was observed between the
      composites containing fibers with diameters of 19 and 26 MUm. CONCLUSION: The
      diameter of the fibers influences the mechanical properties of the FRCs.

PMID- 23965455
TI  - Dental myths, oral hygiene methods and nicotine habits in an ageing rural
      population: an Indian study.
AB  - BACKGROUND: Though, increased emphasis is being given on spreading dental care
      facilities and awareness in Indian villages, the target population is
      unfortunately less literate and is not financially equipped compared to their
      urban counterparts. The rural aged additionally may have to face problems like
      desertion by the educated youth to follow better opportunities in cities,
      disease, and lack of mobility. AIMS: The present study strived to evaluate dental
      myths, oral hygiene methods, and tobacco habits awareness in a rural ageing
      population in the perspective of a changing India. SETTING AND DESIGN: The study
      area consisted of a group of ten villages, situated in district Lucknow, Uttar
      Pradesh, India. MATERIALS AND METHODS: The subjects were questioned about dental
      myths, tobacco habits, and oral hygiene methods and then divided into groups on
      the basis of age, sex, and educational status. The number of sound teeth in each
      subject was also counted. STATISTICAL ANALYSIS: Mean-values, standard deviation,
      Chi-square test and P values were used to make inter-group comparisons. RESULTS
      AND CONCLUSION: Forty percent of the subjects considered oral hygiene
      unnecessary, 60.8% of the population was relying on simple mouth rinsing for
      maintaining oral hygiene, 48% had either the habit of smoking and chewing tobacco
      or both and 81% of the subjects had one dental myth or the other. We concluded
      that the rural aged is a deprived lot and a targeted program to infuse scientific
      dental practices in them is necessary.

PMID- 23965456
TI  - Prevalence of oral lesions in Brazilian patients with tuberculosis.
AB  - BACKGROUND: Oral lesions of tuberculosis (TB) are rare and usually associated
      with the secondary form of the disease. AIM: The aim of the present study was to
      determine the prevalence of oral lesions in a cohort of TB-infected individuals.
      MATERIALS AND METHODS: The study was carried out in two reference centers for the
      treatment of TB in Recife, Brazil. All patients treated for TB in the period from
      July 2008 to March 2009 were included in the study. The data was subjected to
      descriptive statistical analysis. RESULTS: One hundred and twenty-one patients
      were included in the study. A marked male prevalence was observed, with a
      male:female ratio of 6.12:1. HIV coinfection was a common event (33%). Head and
      neck lesions of TB were rare. Cervical node enlargement was observed in seven
      individuals (5.8%) and oral ulceration in one patient (0.8%). DISCUSSION: The low
      prevalence of oral lesions of TB is in accordance with other studies. Nodal
      involvement is the most common form of head and neck disease. CONCLUSION: While
      TB may be a common accompanying feature of HIV disease, orofacial complications
      of TB are rare in individuals resident in northern Brazil.

PMID- 23965457
TI  - Assesment of artificial caries lesions through scanning electron microscopy and
      cross-sectional microhardness test.
AB  - AIMS: To assess through scanning electron microscopy (SEM) and cross-sectional
      microhardness (CSMH) test whether the methodology exposed in this experiment can
      be used to produce artificial active white spot lesions (AAWSLs) on smooth
      unabraded human dental enamel. MATERIALS AND METHODS: Ten human permanent molars
      were used in this experiment. One section of each tooth was double coated with
      nail varnish except for a limited central area sized 2.5 mm * 1 mm (2.5 mm 2 ).
      Each specimen was individually exposed to 10.4 ml of a demineralizing solution at
      pH 5.0, during 42 days (37 degrees C) without agitation. Samples were sectioned
      in the center of the AAWSL and one half was analyzed in SEM and the other half
      was subjected to CSMH. Descriptive statistics was performed to determine mean
      depth of the lesion. RESULTS: The mean depth of AAWSL was 100 MUm (s.d. =12.1)
      and a white dull rough surface could be detected by the unaided eye. SEM images
      demonstrated that although some surface areas of the lesion appeared to be
      relatively intact, erosion was present. A prismatic pattern of dissolution was
      observed in all samples with an enlargement of the prism sheaths and some samples
      had also sites of destruction of prism cores. CONCLUSION: This methodology can be
      used to induce AAWSLs in human dental enamel but surface erosion has to be taken
      into account when performing CSMH test.

PMID- 23965458
TI  - Immunolocalization of Bcl-2 oncoprotein in amlodipine-induced gingival
      overgrowth.
AB  - BACKGROUND: Drug-induced gingival overgrowth (DIGO) is one of the unwanted side
      effects of amlodipine therapy, but the pathogenesis still remains unclear.
      Apoptosis, which plays a ubiquitous role in tissue homeostasis, including
      gingiva, may be involved in the development of gingival enlargement. AIMS AND
      OBJECTIVES: (i) To study the distribution of Bcl-2 in healthy and overgrown
      gingival tissues. (ii) To compare and correlate the Bcl-2 expression in gingival
      samples from subjects on amlodipine therapy to the findings in healthy controls.
      MATERIALS AND METHODS: A total of 25 subjects were recruited for the study - 15
      hypertensive patients and 10 systemically healthy subjects. Both the groups were
      analyzed for Bcl-2 expression using immunohistochemistry. RESULTS: Few of the
      control specimens showed weak positivity to Bcl-2 antibody, with the distribution
      limited to the basal cell layers alone, whereas 10 hyperplastic specimens
      expressed Bcl-2 and, unlike the control group, the distribution pattern was seen
      in both basal and suprabasal layers. CONCLUSION: The results indicate that the
      pathogenesis of amlodipine-induced gingival overgrowth might involve inhibition
      of apoptosis, especially with morphogenesis of hyperplastic gingival epithelia.

PMID- 23965459
TI  - Targeted therapy: A novel approach in head and neck cancer.
AB  - The majority of patients with head and neck cancer present with locally advanced
      disease. Locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN)
      poses one of the most complex management challenges. This stage of disease is
      still potentially curable, but requires combined-modality therapy. One of the
      novel approaches is the use of targeted agents, particularly the epidermal growth
      factor receptor (EGFR) inhibitors, in treatment strategies in LA-SCCHN. A Medline
      search covering topics related to targeted therapies in head and neck cancer over
      the last two decades was made and the facts were compiled. Cetuximab was the
      first novel agent to obtain regulatory approval in the United States for the
      treatment of patients with Head and Neck Squamous Cell Cancer HNSCC. Cetuximab
      has been evaluated in combination with radiotherapy, chemo-radiotherapy, and
      induction chemotherapies, and was found to increase the overall survival rates in
      all the arms without raising the toxicity level of the combined modality of
      treatment significantly. The tyrosine kinase inhibitors Gefinitib and Erlotinib
      also produced an average response rate of 11% and 4% in different studies and
      also prolonged the disease control rates when used with chemotherapy. This paper
      will review the role of targeted agents, particularly the EGFR inhibitors, in the
      present treatment strategies in advanced, recurrent/metastatic head and neck
      cancer. 

PMID- 23965460
TI  - Low level laser therapy in the treatment of aphthous ulcer.
AB  - Recurrent aphthous stomatitis (RAS) is one of the most common and painful
      ulcerative lesions of the oral cavity, but until now no cure has been recognized
      for it. Two patients diagnosed with minor RAS were treated in a single sitting
      with low level laser therapy using 940-nm diode laser. The lesions healed
      completely within 3-4 days and a follow-up for 1 showed no recurrence in these
      patients. According to the results of this study, low level laser therapy can
      decrease the healing time, pain intensity, size, and recurrence of the lesion in
      patients with minor RAS, and hence can be considered the most appropriate
      treatment modality for minor RAS, with greatest clinical effectiveness. 

PMID- 23965461
TI  - Use of extraoral periapical radiography in Indian population: technique and case
      reports.
AB  - Performing intraoral radiography in certain patients is difficult as these
      patients are unable to tolerate intraoral film placement. To assist such patients
      a new technique has been innovated using extraoral film placement. Use of this
      technique has been documented in Caucasian and Taiwanese populations. In this
      paper we report use of this technique for Indian population. We have done about
      40 cases using this technique and have found the average angulation for maxillary
      (-25+/-5 degrees) and mandibular (-15+/-5 degrees) teeth for Indian population.
      We recommend use of this technique in the personal dental clinics where panoramic
      radiographic machines are not readily available. Here we report the technique and
      cases where diagnostic imaging was performed in patients using the extraoral
      periapical technique. 

PMID- 23965462
TI  - Endodontic and post-endodontic management of a fused molar.
AB  - Treatment of fused teeth needs special care and attention to the bizarre anatomy.
      This paper describes root canal treatment of a fused carious tooth presenting
      with apical periodontitis. It is a rare case of fusion of the mandibular second
      molar with a paramolar. There is no literature regarding placement of crown over
      endodontically treated fused teeth. In this case, the fused teeth were
      endodontically treated and restored by a porcelain fused to metal crown. 

PMID- 23965463
TI  - Histomorphometric analysis of nuclear and cellular volumetric alterations in oral
      lichen planus, lichenoid lesions and normal oral mucosa using image analysis
      software.
AB  - INTRODUCTION: Lichen planus is a chronic inflammatory mucocutaneous disease that
      clinically and histologically resembles lichenoid lesions, although the latter
      has a different etiology. Though criteria have been suggested for differentiating
      oral lichen planus from lichenoid lesions, confusion still prevails. AIMS: To
      study the cellular and nuclear volumetric features in the epithelium of normal
      mucosa, lichen planus, and lichenoid lesions to determine variations if any.
      MATERIALS AND METHODS: A retrospective study was done on 25 histologically
      diagnosed cases each of oral lichen planus, oral lichenoid lesions, and normal
      oral mucosa. Cellular and nuclear morphometric measurements were assessed on
      hematoxylin and eosin sections using image analysis software. STATISTICAL
      ANALYSIS: Analysis of variance test (ANOVA) and Tukey's post-hoc test. RESULTS:
      The basal cells of oral lichen planus showed a significant increase in the mean
      nuclear and cellular areas, and in nuclear volume; there was a significant
      decrease in the nuclear-cytoplasmic ratio as compared to normal mucosa. The
      suprabasal cells showed a significant increase in nuclear and cellular areas,
      nuclear diameter, and nuclear and cellular volumes as compared to normal mucosa.
      The basal cells of oral lichenoid lesions showed significant difference in the
      mean cellular area and the mean nuclear-cytoplasmic ratio as compared to normal
      mucosa, whereas the suprabasal cells differed significantly from normal mucosa in
      the mean nuclear area and the nuclear and cellular volumes. CONCLUSIONS:
      Morphometry can differentiate lesions of oral lichen planus and oral lichenoid
      lesions from normal oral mucosa. Thus, morphometry may serve to discriminate
      between normal and premalignant lichen planus and lichenoid lesions. These
      lesions might have a high risk for malignant transformation and may behave in a
      similar manner with respect to malignant transformation.

PMID- 23965464
TI  - Bilateral fusion in primary mandibular teeth.
AB  - Fusion has been described as a developmental anomaly characterized by the union
      of two adjacent teeth. Few cases of this rare anomaly in primary dentition have
      been reported in Indian population. A rare case of bilateral fusion between
      primary mandibular lateral incisors and canines is presented in this report. 

PMID- 23965465
TI  - Guided bone regeneration in the treatment of fenestration osseous defect.
AB  - This article presents a case with a fenestration defect which was treated by
      placing a resorbable barrier alone. In the case presented, the osseous defect was
      a natural space maker with the wall of the defect providing sufficient support to
      prevent collapse of the membrane into the space. So the use of membrane alone is
      the preferred treatment. Resorbable collagen membrane was placed in order to
      avoid a second surgical procedure to remove the nonresorbable membrane. The
      membrane was positioned by placing a resorbable sling suture such that it covered
      the defective site adequately. Postsurgical healing of the defect was evaluated 1
      month after the surgery and it was satisfactory. Thus guided bone regeneration of
      the fenestration defect is a reliable treatment procedure. 

PMID- 23965466
TI  - Laser vaporization of extravasation type of mucocele of the lower lip with 940-nm
      diode laser.
AB  - A 43-year-old male presented with an asymptomatic swelling of the lower labial
      mucosa. Examination revealed that the tip of maxillary canine was causing trauma
      on the affected side. A diagnosis of extravasation type of mucocele was
      established clinically. Vaporization of the mucocele was done with a 940-nm diode
      laser in contact mode. The lesion healed uneventfully and there has been no
      recurrence for 3 months. 

PMID- 23965467
TI  - Geographic differences in outcomes in outpatients with established
      atherothrombotic disease: results from the REACH Registry.
AB  - AIMS: There are major differences in the prevalence and management of patients
      with atherothrombotic disease including coronary artery disease (CAD),
      cerebrovascular disease (CVD) and peripheral artery disease (PAD) across
      different geographical regions. There is, however, little data allowing
      comparisons of management and outcomes across broad geographic regions. We aimed
      to describe geographical differences in baseline characteristics, management and
      outcomes in stable outpatients with established atherothrombotic disease. METHODS
      AND RESULTS: From the REACH Registry of atherothrombosis, patients with
      documented CAD, PAD or CVD and with 4-year follow-up were included. Baseline
      characteristics, treatments and 4-year outcomes were recorded. Event rates were
      compared between geographical regions and were adjusted for risk scores
      predicting ischemic and bleeding events. The analyses of baseline characteristics
      and medications according to geographical region showed marked differences. For
      the composite primary outcome (cardiovascular death, non-fatal myocardial
      infarction (MI) and non-fatal stroke), rates ranged from 12.1% in Japan to 18.2%
      in Eastern Europe. After adjustment, substantial variations remained: taking
      North America as a reference, patients from Western Europe and Japan had a lower
      risk of primary outcome event (hazard ratio (HR) 0.93; p = 0.045, and HR = 0.67;
      p < 0.001 respectively) whereas patients from Eastern Europe had a higher risk
      (HR = 1.24; p < 0.001). There were no obvious differences between patients from
      North America and those from Latin America, the Middle East and Asia. CONCLUSION:
      There are important variations in the outcomes of patients with atherothrombotic
      across geographic regions. These observations have important implications for
      public health and clinical research.

PMID- 23965468
TI  - A missense mutation in DUSP6 is associated with Class III malocclusion.
AB  - Class III malocclusion is a common dentofacial phenotype with a variable
      prevalence according to ethnic background. The etiology of Class III malocclusion
      has been attributed mainly to interactions between susceptibility genes and
      environmental factors during the morphogenesis of the mandible and maxilla. Class
      III malocclusion shows familial recurrence, and family-based studies support a
      predominance of an autosomal-dominant mode of inheritance. We performed whole
      exome sequencing on five siblings from an Estonian family affected by Class III
      malocclusion. We identified a rare heterozygous missense mutation, c.545C>T
      (p.Ser182Phe), in the DUSP6 gene, a likely causal variant. This variant co
      segregated with the disease following an autosomal-dominant mode of inheritance
      with incomplete penetrance. Transcriptional activation of DUSP6 has been presumed
      to be regulated by FGF/FGFR and MAPK/ERK signaling during fundamental processes
      at early stages of skeletal development. Several candidate genes within a linkage
      region on chromosome 12q22-q23--harboring DUSP6--are implicated in the regulation
      of maxillary or mandibular growth. The current study reinforces that the 12q22
      q23 region is biologically relevant to craniofacial development and may be
      genetically linked to the Class III malocclusion.

PMID- 23965470
TI  - Does a liberal national transfusion law assure blood safety? A survey of blood
      bank directors' perspectives in Lebanon.
AB  - In transfusion medicine today, 'zero risk' has become a universal objective.
      Thus, we investigated whether the level of blood safety as defined by Lebanese
      legislation is satisfactory. Our work covered the period from September 2008 to
      June 2012. First, we studied each chapter in law and regulations, and compared
      them with the latest French regulations. The standards of Good Manufacturing
      Practice, characteristics of blood products and their storage, and the overall
      organization and haemovigilance for recipients and donors are not defined. Our
      analysis revealed numerous problems in today's blood safety situation. There is,
      for example, no clear definition or identification of the different blood safety
      components. Then, we conducted a national survey of blood bank directors to
      assess their perception of blood safety in Lebanon. Our survey revealed a
      negative perception (52.4 per cent) of the current blood safety situation, with
      more than 90 per cent of respondents in favor of national regulatory
      improvements. 

PMID- 23965471
TI  - HIV immune activation drives increased Eomes expression in memory CD8 T cells in
      association with transcriptional downregulation of CD127.
AB  - BACKGROUND: During HIV infection distinct mechanisms drive immune activation of
      the CD4 and CD8 T cells leading to CD4 T-cell depletion and expansion of the CD8
      T-cell pool. This immune activation is polyclonal and extends beyond HIV-specific
      T cells. One consequence of this immune activation is a profound decrease in IL
      7Ralpha (CD127) expression on memory CD8 T cells. The mechanisms leading to this
      are unknown and because of the potential impact of reduced IL-7 signaling in
      memory T cells specific to HIV and other pathogens, in the present study we
      examined the molecular mechanisms implicated in this downregulation of CD127.
      METHODS: Membrane bound (mIL7RA) and soluble (sIL7RA) mRNA expression was
      determined by qRT-PCR. CD127, Eomesodermin (Eomes) and T-bet expression in
      healthy controls and HIV-infected patients were studied by flow cytometry.
      RESULTS: CD127 downregulation occurs at the transcriptional level for both mIL7RA
      and sIL7RA alternative spliced forms in the CD127 memory CD8 T cells. CD127
      memory CD8 T cells exhibited increased Eomes expression and an 'effector-like'
      gene profile. These changes were associated with higher HIV-RNA levels. Following
      combination antiretroviral therapy (cART), there was an increase in CD127
      expression over an extended period of time (>5 months) which was associated with
      decreased Eomes expression. CONCLUSION: CD127 is downregulated at a
      transcriptional level in memory CD8 T cells in association with upregulation of
      Eomes expression.

PMID- 23965472
TI  - Causes and significance of markedly elevated serum ferritin levels in an academic
      medical center.
AB  - OBJECTIVE: A markedly elevated serum ferritin level has been associated with
      inflammatory conditions such as adult-onset Still's disease, systemic juvenile
      idiopathic arthritis, and hemophagocytic lymphohistiocytosis/macrophage
      activation syndrome. Hyperferritinemia, however, can also be caused by a wide
      variety of disparate conditions, often with impressively high serum levels. The
      objective of this analysis was to investigate the underlying etiology of markedly
      elevated ferritin levels in a large group of patients treated as outpatients and
      inpatients in a tertiary-care medical center. METHODS: Data of all adult patients
      from 2008 through 2010 with at least 1 serum ferritin level greater than 1000
      MUg/L were reviewed. If a patient had multiple qualifying levels, the highest one
      was used. For each case, the most likely cause of the elevated ferritin was
      assessed based on the available clinical data using a simple algorithmic
      approach. RESULTS: Six hundred twenty-seven patients were found. The average
      serum ferritin level was 2647 MUg/L. The most frequent condition was malignancy
      (153/627), with iron-overload syndromes the second most common (136/627). There
      were 6 cases of adult-onset Still's disease, systemic juvenile idiopathic
      arthritis, or hemophagocytic lymphohistiocytosis/macrophage activation syndrome.
      The average ferritin level in these syndromes was 14242 MUg/L. Seven patients
      appeared to have anemia of chronic inflammation, and in 5 patients, there was no
      clearly definable cause for hyperferritinemia. CONCLUSIONS: Although extremely
      elevated ferritin levels may be associated with rheumatologic diseases, more
      often they are found in patients with other conditions such as malignancy or
      infection. In addition, extremely high ferritin levels can be found in patients
      with seemingly indolent disease or levels of chronic inflammation.

PMID- 23965473
TI  - A 22-year-old man with severe osteoporosis due to prolactinoma.
AB  - Prolactin-secreting adenomas represent nearly 40% to 60% of all pituitary
      adenomas. Prolactin inhibits the secretion of gonadotropin-releasing hormone that
      is responsible for the synthesis and secretion of gonadotropins. Sex steroids
      have an important effect on the regulation of bone metabolism in men. Decreased
      libido and impotence are the most common presenting symptoms of
      hyperprolactinemia in males. These symptoms are easily neglected by both patients
      and some physicians. We present a 22-year-old man with multiple osteoporotic
      fractures associated with prolactinoma despite the use of teriparatide for 18
      months. We emphasize and highlight the importance of hyperprolactinemia and
      fractures caused by high prolactin levels. 

PMID- 23965474
TI  - Takayasu arteritis presenting in the context of active tuberculosis: a pediatric
      case.
AB  - Takayasu arteritis (TA) is a large-vessel vasculitis, most commonly presenting in
      young adults and more rarely in pediatric patients. An apparent association
      between TA and Mycobacterium tuberculosis has been noted previously, although
      this potential relationship is not yet understood. We present the case of a 16
      year-old Haitian girl diagnosed with TA, originally presenting in the context of
      active tuberculosis. Our patient has been treated with antituberculosis therapy,
      corticosteroids, methotrexate, and rituximab to control her continued active
      vasculitis. With this case report, we seek to promote further exploration of the
      apparent association between TA and tuberculosis, as further clarification of the
      nature of this relationship may lead to the development of more targeted
      therapies and better outcomes for TA patients. 

PMID- 23965475
TI  - Primary antiphospholipid syndrome and necrotizing pancreatitis: a diagnostic
      challenge.
AB  - The objective of this study was to report an unusual case of primary
      antiphospholipid syndrome (APS)-associated severe necrotizing pancreatitis. Since
      the APS was first recognized in the 1980s, a number of manifestations of the
      disorder have been described. We report primary APS presenting as severe
      necrotizing pancreatitis. This is the first such case to date that fulfills the
      revised Sapporo classification criteria. A 38-year-old previously healthy woman
      presented with new-onset hypertensive emergency and acute kidney injury. She
      subsequently developed severe epigastric pain attributable to necrotizing
      pancreatitis and extensive splenic infarcts. Biopsies of both the pancreas and
      kidney revealed thrombotic microangiopathy. Her lupus anticoagulant was positive
      on both weeks 1 and 12 of her disease course. A diagnosis of primary APS was
      made. Despite 6 months of aggressive care, she died of sepsis. 

PMID- 23965476
TI  - Rheumatoid arthritis and tracheal chondritis complicated by pulmonary
      nontuberculous mycobacteria infection.

PMID- 23965477
TI  - Rituximab-induced serum sickness in overlapping syndrome between sjogren syndrome
      and systemic lupus erythematosus.

PMID- 23965479
TI  - Comparison of physician and patient global assessments over time in patients with
      rheumatoid arthritis: a retrospective analysis from the RADIUS cohort.
AB  - BACKGROUND: In rheumatoid arthritis (RA), there is discordance between patient
      and physician assessments of disease severity and treatment response. OBJECTIVE:
      This retrospective analysis of the RADIUS (RA Disease-Modifying Anti-Rheumatic
      Drug Intervention and Utilization Study) 1 cohort examined specific factors that
      influence differences in global assessments for therapeutic effectiveness of
      disease-modifying antirheumatic drugs made by physicians (physician global
      assessment [PhGA]) and patients (patient global assessment [PtGA]). METHODS: The
      RADIUS 1 cohort consisted of primarily community-based private practice patients
      with RA requiring either the addition of or a switch to a new biologic or
      nonbiologic disease-modifying antirheumatic drug and who were followed for up to
      5 years by their rheumatologists. Periodic assessments included PhGA, PtGA,
      Health Assessment Questionnaire-Disability Index (HAQ-DI), 28-item tender/painful
      joint count (TJC28), swollen joint count (SJC28), pain Visual Analog Scale (VAS),
      and acute-phase reactants. RESULTS: Among 4359 patients (mean disease duration,
      7.3 years), PhGA most highly correlated with TJC28 (0.6956; 95% confidence
      interval [CI], 0.6881-0.7030) and SJC28 (0.6757; 95% CI, 0.6678-0.6834). Moderate
      overall correlations were observed for PtGA with TJC28 (0.5000; 95% CI, 0.4890
      0.5108) and less 50 with SJC28 (0.3754; 95% CI, 0.3628-0.3878). Patient global
      assessment most strongly correlated with pain VAS (0.8349; 95% CI, 0.8305-0.8392)
      and moderately correlated with HAQ-DI (0.5979; 95% CI, 0.5886-0.6071). Acute
      phase reactants poorly correlated with PhGA and PtGA. CONCLUSIONS: Low
      correlations between PhGA and acute-phase reactants suggest that these
      measurements have a limited contribution compared with the physical examination
      when physicians make global assessments. These results also suggest that
      physicians should consider patients' assessments of their disease activity (HAQ,
      pain VAS, and PtGA) and put joint counts into proper context.

PMID- 23965481
TI  - A Renaissance Pope with arthritis following frostbite.
AB  - Pius II, a 15th century Pope, developed chronic foot pain following frostbite at
      age 30. Later in life he was progressively disabled by arthritis elsewhere and by
      colic, which may have been due to kidney stones. The differential diagnosis of
      his rheumatic disease and its effect on his career are discussed. 

PMID- 23965480
TI  - Integrating acupuncture with exercise-based physical therapy for knee
      osteoarthritis: a randomized controlled trial.
AB  - BACKGROUND: Knee osteoarthritis is a chronic disease associated with significant
      morbidity and economic cost. The efficacy of acupuncture in addition to
      traditional physical therapy has received little study. OBJECTIVE: The objective
      of this study was to compare the efficacy and safety of integrating a
      standardized true acupuncture protocol versus nonpenetrating acupuncture into
      exercise-based physical therapy (EPT). METHODS: This was a randomized, double
      blind, controlled trial at 3 physical therapy centers in Philadelphia, PA. We
      studied 214 patients (66% African Americans) with at least 6 months of chronic
      knee pain and x-ray-confirmed Kellgren scores of 2 or 3. Patients received 12
      sessions of acupuncture directly following EPT over 6 to 12 weeks. Acupuncture
      was performed at the same 9 points dictated by the traditional Chinese "Bi"
      syndrome approach to knee pain, using either standard needles or Streitberger non
      skin-puncturing needles. The primary outcome was the proportion of patients with
      at least a 36% improvement in Western Ontario and McMaster Universities
      Osteoarthritis Index score at 12 weeks. RESULTS: Both treatment groups showed
      improvement from combined therapy with no difference between true (31.6%) and
      nonpenetrating acupuncture (30.3%) in Western Ontario and McMaster Universities
      Osteoarthritis Index response rate (P = 0.5) or report of minor adverse events. A
      multivariable logistic regression prediction model identified an association
      between a positive expectation of relief from acupuncture and reported
      improvement. No differences were noted by race, sex, or age. CONCLUSIONS:
      Puncturing acupuncture needles did not perform any better than nonpuncturing
      needles integrated with EPT. Whether EPT, acupuncture, or other factors accounted
      for any improvement noted in both groups could not be determined in this study.
      Expectation for relief was a predictor of reported benefit.

PMID- 23965482
TI  - Incidence and prevalence of polymyositis and dermatomyositis in a health
      management organization in Buenos Aires.
AB  - BACKGROUND: Polymyositis (PM) and dermatomyositis (DM) are infrequent diseases.
      Data on incidence and prevalence are scarce and conflicting. There are no such
      data in Latin America and in Argentina in particular. OBJECTIVES: We undertook to
      examine the incidence and prevalence of PM/DM in the prepaid health maintenance
      organization (HMO) of our hospital, in the city of Buenos Aires. METHODS: Members
      of the HMO between January 1999 and June 2009 were identified from medical
      records of patients followed up by us at the HMO. Incident cases and prevalence
      were calculated at the end of the period. RESULTS: During the study period,
      146,747 persons contributed a total of 937,902.6 person-years (mean age was 46.6
      [SD, 18.4] years, and 59% were female). Ten incident cases were detected, 7 women
      and 3 men with a global incidence rate (IR) of 1.07 per 100,000 person-years (95%
      confidence interval [CI], 0.5-1.84). Three subjects had DM with an IR of 0.32 per
      100,000 person-years (95% CI, 0.1-0.99), and 7 had PM with an IR of 0.75 per
      100,000 person-years (95% CI, 0.35-0.16). On June 1, 2009, 17 prevalent cases
      were detected, with a mean age of 48.9 (SD, 17.7) years; 76% were female,
      representing a prevalence of 17.4 per 100,000 persons (95% CI, 10.1-27.8). Among
      the 17 patients with idiopathic inflammatory myopathy, 10 patients had DM, with a
      prevalence of 10.22 per 100,000 persons (95% CI, 4.9-18.8), and 7 had PM
      (prevalence, 7.2 per 100,000 persons [95% CI, 2.9-14.7]). CONCLUSIONS: It is
      difficult to compare studies from different populations and using different
      ascertainment techniques. These first data from Latin America are in general
      agreement with many studies.

PMID- 23965483
TI  - Report from the Latin American Spondyloarthritis Society for Education and
      Research in Immunology and Medicine organization 2012 workshop.
AB  - The first annual meeting of the Latin American Spondyloarthritis Society for
      Education and Research in Immunology and Medicine (LASSERIM) was held in Bogota,
      Colombia, in September 2012 and was attended by key opinion leaders, researchers,
      and rheumatologists. The meeting included presentations and discussions from
      renowned speakers during 2 days and a coaching leadership exercise led by an
      expert in the field followed by an open forum. Two groups defined a priori
      discussed the establishment of a professional network and organization to be
      involved in the identification, assessment, and effective resolution of health
      care issues in Latin America.A broad spectrum of topics were discussed but
      focused on the following: pharmacoeconomics in general rheumatology,
      spondyloarthritis and chronic back pain, therapeutic interventions in rheumatoid
      arthritis, ultrasonography in spondyloarthritis, impact of social media in
      medicine and global trends in leadership, quality of life, and innovation. A
      special workshop on coaching in health care and coaching as a tool to implement
      LASSERIM goals was part of the 2-day conference.LASSERIM will be working in the
      future on education, research, and innovation in the field of rheumatology and
      immunology. A special focus will be on spondyloarthritis, by promoting research,
      open discussions, and by conducting carefully planned research studies to impact
      on the quality of life of patients and doctors from Latin American countries. 

PMID- 23965484
TI  - Posterior reversible encephalopathy syndrome in systemic lupus erythematosus.
AB  - BACKGROUND/OBJECTIVE: Posterior reversible encephalopathy syndrome (PRES) is an
      underrecognized and reversible condition in systemic lupus erythematosus (SLE)
      that could mimic neuropsychiatric lupus. Identification of any distinct clinical
      patterns is important as one would need to escalate rather than decrease or
      discontinue immune suppression in neuropsychiatric lupus. METHODS: We
      retrospectively identified and described 5 patients with SLE who were
      hospitalized and diagnosed with PRES from 2008 to 2013 in a tertiary medical
      center and reviewed relevant literature. RESULTS: Posterior reversible
      encephalopathy syndrome in SLE occurred in young women with age distribution from
      19 to 37 years. At the time of presentation, all had hypertension (systolic blood
      pressures ranging from 150 to 220), moderate to severe disease activity (Systemic
      Lupus Erythematosus Disease Activity Index scores ranging from 11 to 41), and
      prototypical magnetic resonance imaging findings of PRES and nephritis (4 of 5
      patients had biopsy-proven lupus nephritis). Seizures, headache, and confusion
      were the most common clinical symptoms. One patient had intracerebral hematoma,
      and 2 patients had cerebral petechial hemorrhages. All patients improved without
      any neurological deficits, with a mean hospital stay of 11.2 days. CONCLUSIONS:
      Systemic lupus erythematosus should be considered in the differential diagnosis
      of patients who present with PRES. One should have a low threshold for magnetic
      resonance imaging especially when neurological symptoms occur in young women with
      or without an established diagnosis of SLE and especially among those with active
      SLE, lupus nephritis, renal failure, and/or poorly controlled hypertension. Given
      the good prognosis of PRES in SLE patients with early supportive treatment,
      prompt recognition is crucial to institute appropriate management.

PMID- 23965485
TI  - Clinical use of anti-cyclic citrullinated peptide antibody testing.

PMID- 23965486
TI  - Sacroiliitis in Behcet syndrome.

PMID- 23965487
TI  - Crowned dens syndrome and cervical interspinous bursitis mimicking acute
      meningitis.

PMID- 23965488
TI  - The prevalence and prognostic significance of right ventricular systolic
      dysfunction in nonischemic dilated cardiomyopathy.
AB  - BACKGROUND: Cardiovascular magnetic resonance is the gold-standard technique for
      the assessment of ventricular function. Although left ventricular volumes and
      ejection fraction are strong predictors of outcome in dilated cardiomyopathy
      (DCM), there are limited data regarding the prognostic significance of right
      ventricular (RV) systolic dysfunction (RVSD). We investigated whether
      cardiovascular magnetic resonance assessment of RV function has prognostic value
      in DCM. METHODS AND RESULTS: We prospectively studied 250 consecutive DCM
      patients with the use of cardiovascular magnetic resonance. RVSD, defined by RV
      ejection fraction<=45%, was present in 86 (34%) patients. During a median follow
      up period of 6.8 years, there were 52 deaths, and 7 patients underwent cardiac
      transplantation. The primary end point of all-cause mortality or cardiac
      transplantation was reached by 42 of 86 patients with RVSD and 17 of 164 patients
      without RVSD (49% versus 10%; hazard ratio, 5.90; 95% confidence interval [CI],
      3.35-10.37; P<0.001). On multivariable analysis, RVSD remained a significant
      independent predictor of the primary end point (hazard ratio, 3.90; 95% CI, 2.16
      7.04; P<0.001), as well as secondary outcomes of cardiovascular mortality or
      cardiac transplantation (hazard ratio, 3.35; 95% CI, 1.76-6.39; P<0.001), and
      heart failure death, heart failure hospitalization, or cardiac transplantation
      (hazard ratio, 2.70; 95% CI, 1.32-5.51; P=0.006). Assessment of RVSD improved
      risk stratification for all-cause mortality or cardiac transplantation (net
      reclassification improvement, 0.31; 95% CI 0.10-0.53; P=0.001). CONCLUSIONS: RVSD
      is a powerful, independent predictor of transplant-free survival and adverse
      heart failure outcomes in DCM. Cardiovascular magnetic resonance assessment of RV
      function is important in the evaluation and risk stratification of DCM patients.

PMID- 23965489
TI  - Levels and changes of HDL cholesterol and apolipoprotein A-I in relation to risk
      of cardiovascular events among statin-treated patients: a meta-analysis.
AB  - BACKGROUND: It is unclear whether levels of high-density lipoprotein cholesterol
      (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with
      cardiovascular risk among patients who achieve very low levels of low-density
      lipoprotein cholesterol on statin therapy. It is also unknown whether a rise in
      HDL-C or apoA-I after initiation of statin therapy is associated with a reduced
      cardiovascular risk. METHODS AND RESULTS: We performed a meta-analysis of 8
      statin trials in which lipids and apolipoproteins were determined in all study
      participants at baseline and at 1-year follow-up. Individual patient data were
      obtained for 38,153 trial participants allocated to statin therapy, of whom 5387
      suffered a major cardiovascular event. HDL-C levels were associated with a
      reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83;
      95% confidence interval [CI], 0.81-0.86 per 1 standard deviation increment), as
      were apoA-I levels (HR, 0.79; 95% CI, 0.72-0.82). This association was also
      observed among patients achieving on-statin low-density lipoprotein cholesterol
      levels <50 mg/dL. An increase of HDL-C was not associated with reduced
      cardiovascular risk (HR, 0.98; 95% CI, 0.94-1.01 per 1 standard deviation
      increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90-0.97).
      CONCLUSIONS: Among patients treated with statin therapy, HDL-C and apoA-I levels
      were strongly associated with a reduced cardiovascular risk, even among those
      achieving very low low-density lipoprotein cholesterol. An apoA-I increase was
      associated with a reduced risk of major cardiovascular events, whereas for HDL-C
      this was not the case. These findings suggest that therapies that increase apoA-I
      concentration require further exploration with regard to cardiovascular risk
      reduction.

PMID- 23965490
TI  - External Quality Assessment (EQA) program for the preanalytical and analytical
      immunohistochemical determination of HER2 in breast cancer: an experience on a
      regional scale.
AB  - BACKGROUND: An External Quality Assessment (EQA) program was developed to
      investigate the state of the art of HER2 immunohistochemical determination in
      breast cancer (BC) in 16 Pathology Departments in the Lazio Region (Italy). This
      program was implemented through two specific steps to evaluate HER2 staining
      (step 1) and interpretation (step 2) reproducibility among participants. METHODS:
      The management activities of this EQA program were assigned to the Coordinating
      Center (CC), the Revising Centers (RCs) and the Participating Centers (PCs). In
      step 1, 4 BC sections, selected by RCs, were stained by each PC using their own
      procedures. In step 2, each PC interpreted HER2 score in 10 BC sections stained
      by the CC. The concordance pattern was evaluated by using the kappa category
      specific statistic and/or the weighted kappa statistic with the corresponding 95%
      Jackknife confidence interval. RESULTS: In step 1, a substantial/almost perfect
      agreement was reached between the PCs for scores 0 and 3+ whereas a moderate and
      fair agreement was observed for scores 1+ and 2+, respectively.In step 2, a fully
      satisfactory agreement was observed for 6 out of the 16 PCs and a quite
      satisfactory agreement was obtained for the remaining 10 PCs. CONCLUSIONS: Our
      findings highlight that in the whole HER2 evaluation process the two intermediate
      categories, scores 1+ and 2+, are less reproducible than scores 0 and 3+. These
      findings are relevant in clinical practice where the choice of treatment is based
      on HER2 positivity, suggesting the need to share evaluation procedures within
      laboratories and implement educational programs.

PMID- 23965492
TI  - Pathogenic role of modified LDL antibodies and immune complexes in
      atherosclerosis.
AB  - There is strong evidence supporting a key role of the adaptive immune response in
      atherosclerosis, given that both activated Th cells producing predominantly
      interferon-gamma and oxidized LDL (oxLDL) and the corresponding antibodies have
      been isolated from atheromatous plaques. Studies carried out using immune
      complexes (IC) prepared with human LDL and rabbit antibodies have demonstrated
      proatherogenic and pro-inflammatory properties, mostly dependent on the
      engagement of Fcgamma receptors I and II in macrophages and macrophage-like cell
      lines. Following the development of a methodology for isolating modified LDL
      (mLDL) antibodies from serum and isolated IC, it was confirmed that antibodies
      reacting with oxLDL and advanced glycation end product-modified LDL are
      predominantly IgG of subtypes 1 and 3 and that mLDL IC prepared with human
      reagents possesses pro-inflammatory and proatherogenic properties. In previous
      studies, LDL separated from isolated IC has been analyzed for its modifications,
      and the reactivity of antibodies isolated from the same IC with different LDL
      modifications has been tested. Recently, we obtained strong evidence suggesting
      that the effects of mLDL IC on phagocytic cells are modulated by the composition
      of the mLDL. Clinical studies have shown that the level of mLDL in circulating IC
      is a strong predictor of cardiovascular disease (CVD) and, in diabetic patients,
      other significant complications, such as nephropathy and retinopathy. In
      conclusion, there is convincing ex vivo and clinical data supporting the
      hypothesis that, in humans, the humoral immune response to mLDL is pathogenic
      rather than protective. 

PMID- 23965491
TI  - Rationale, design, and baseline characteristics of a trial for the prevention of
      diabetic atherosclerosis using a DPP-4 inhibitor: the Study of Preventive Effects
      of Alogliptin on Diabetic Atherosclerosis (SPEAD-A).
AB  - AIM: Alogliptin, an efficacious inhibitor of DPP-4 that improves glycemic
      control, as well as the pancreatic beta-cell function, is now increasingly used
      to accomplish glycemic targets in type 2 diabetic patients. Interestingly, recent
      experimental studies have shown that alogliptin exerts anti-atherosclerotic
      effects in GLP-1-dependent and -independent manners. The aim of the present
      ongoing study is to investigate the preventive effects of alogliptin on the
      progression of atherosclerosis in type 2 diabetic subjects using the carotid
      intima-media thickness (IMT), an established marker of cardiovascular disease.
      METHODS AND RESULTS: The Study of Preventive Effects of Alogliptin on Diabetic
      Atherosclerosis (SPEAD-A) is a prospective, randomized, open-label, blinded
      endpoint, multicenter, parallel-group, comparative study. Between March 2011 and
      March 2012, 341 participants were recruited at 11 clinical sites, and were
      randomly allocated either to an alogliptin treatment group (172 patients) or a
      conventional treatment group (169 patients). The primary outcomes are the changes
      in the maximum and mean IMT of the common carotid artery during a 24-month
      treatment period, as measured by carotid arterial echography. The secondary
      outcomes include the changes in glycemic control, parameters related to beta-cell
      function and diabetic nephropathy, the occurrence of cardiovascular events and
      adverse events and biochemical measurements reflecting vascular function.
      CONCLUSIONS: This is the first study to address the effects of DPP-4 inhibitors
      on the progression of changes in the carotid IMT, with the patients without DPP-4
      inhibitor treatment serving as a control group. The results will be available
      soon, and these findings are expected to provide clinical data that will be
      helpful in the prevention of diabetic atherosclerosis and subsequent
      cardiovascular disease.

PMID- 23965493
TI  - Diagnostic usefulness of ultrasonography for plantar angioleiomyoma.

PMID- 23965494
TI  - Prescription-quality improvement in pharmaceutical compounding.

PMID- 23965495
TI  - Compounded analgesic therapy for disorders of movement: arthritis, neuropathic
      pain, and postpolio syndrome.
AB  - Pain caused by disorders of movement is often chronic and severe and may not be
      alleviated by commercially available medications. In such cases, the use of a
      compounded formulation can provide relief, either as sole therapy or as part of a
      combination treatment regimen. In this report, we review the effects of
      compounded analgesic preparations on chronic severe pain like that produced by
      arthritis, neuropathy, or postpolio syndrome. Case reports are included,
      formulations are presented, and two patients (one of whom, RFM III, is a coauthor
      of this paper) with a painful movement disorder describe their response to custom
      compounded therapy. 

PMID- 23965496
TI  - The role of sex hormones on fibromyalgia pain mediators.
AB  - Understanding the role of the sex hormones in the pain mechanisms and various
      effects on nociceptors is imperative to managing potential underlying hormone
      disruptions in chronic pain syndromes. The myriad of overlapping symptoms between
      mid-life hormone imbalances and mid-life onset of fibromyalgia syndrome in women
      indicates a role for sex hormones in the etiology of fibromyalgia syndrome, which
      is, as of yet, unsupported by the literature. However, fibromyalgia treatment
      should be tailored to the individual needs of the patient, and adrenal, thyroid,
      and ovarian hormone support can lessen the painful burden of fibromyalgia through
      the modulation of various hormone-regulated pain-production pathways. 

PMID- 23965497
TI  - Topical medications for orofacial neuropathic pain.
AB  - The primary advantage of the treatment modalities discussed in this article is
      the potential to provide relief of neuropathic pain without the associated side
      effects of systemic therapies. By working closely with a dental practitioner to
      help formulate the best pharmaceutical therapy for patients, the compounding
      pharmacist has become an essential member of the healthcare team for practicing
      dentists. 

PMID- 23965498
TI  - Managing pain with transdermal ketoprofen.
AB  - Successful treatment of acute and chronic pain has been and continues to be a
      challenge for physicians and pharmacists alike. This article includes a brief
      discussion about the differences between acute and chronic pain and discusses the
      use of transdermal medications for the treatment of pain. Traditional oral drug
      therapies, although effective, can have detrimental side effects that prohibit
      their use. Compounded transdermal ketoprofen offers practitioners a viable
      treatment option and alternative dosage form for nonsteroidal anti-inflammatory
      drug therapy with decreased systemic side effects. 

PMID- 23965499
TI  - Potential treatments for radiation dermatitis.
AB  - Radiation therapy used alone or in combination with chemotherapy and/or surgery
      for the treatment of cancer can be extremely problematic and painful to the
      patient. The adverse effects of radiation therapy include dryness, itching,
      peeling, or blistering of the skin. There are numerous formulas and compounds
      that can be utilized to help patients with radiation burns. The compounding
      pharmacist, physician, and patient can work together to help increase the quality
      of life for a patient that is undergoing a treatment that can be very mentally
      and physically painful. This article discusses some of the agents used by
      compounding pharmacists to provide medicinal alternatives to cater to a cancer
      patient's individualized needs. 

PMID- 23965500
TI  - Compounded gabapentin suspension for lower back pain in an older cat: a case
      report.
AB  - Lower back pain in cats, especially that caused by intervertebral disk disease,
      inhibits movement, greatly compromises quality of life, and, without treatment
      can persist unabated long term. The basic diagnostic workup available to many
      feline patients with low back discomfort can yield inconclusive results, and in
      confirmed cases of intervertebral disk disease, decompression surgery can be
      relatively expensive for the client and not without risk to the patient. Thus
      empirical treatment with an effective analgesic that is safe for and well
      tolerated by cats with low back pain is a welcome and reasonable option for many
      pet owners. In this case report, the use of a compounded suspension of gabapentin
      in an older cat with suspected lumbosacral intervertebral disk disease is
      described. That preparation was prescribed because commercially available tablets
      of gabapentin cannot be split to yield an accurate dose for this feline patient
      and manufactured gabapentin solution, which is not available as a generic but
      only as the branded product Neurontin, contains xylitol, which can be toxic to
      cats. 

PMID- 23965501
TI  - Quality-control: continuous quality improvement.
AB  - This article will help clarify the value in implementing an effective continuous
      quality improvement program in a compounding pharmacy and how a program like this
      can be critical to long-term success. Discussed in this article are: the key
      elements associated with every continuous quality improvement program, how using
      a systematic approach to implementation can add tremendous value, and the roles
      and responsibilities of the individuals that need to be involved with the
      implementation and management of a successful continuous quality improvement
      program. When implemented properly, continuous quality improvement can be
      transformative to an organization by minimizing risks, lowering costs, and
      growing their business. 

PMID- 23965502
TI  - Basics of compounding: compounding with hydrates and solvates.
AB  - As a practitioner, a pharmacist must understand that the most important
      consideration before compounding a preparation should be confirmation of the
      purity and form of all ingredients used, especially active pharmaceutical
      ingredients. It should be determined whether the dose is based on the "base",
      "salt", or "ester" form, etc. Also, many of the ingredients used in compounding
      are solvates, hydrated, or have allowable water content in the powders, and for
      those ingredients, allowances must be made based upon the water content of the
      drug. It is vitally important to refer to the Certificate of Analysis for this
      information. A pharmacist how to properly package, store, and weigh the different
      ingredients used in compounding. This article, which represents the first of a
      series of articles, discusses how the presence of "water" can affect the strength
      of the final compounded preparation. 

PMID- 23965503
TI  - Compounding rifampin suspensions with improved injectability for nasogastric
      enteral feeding tube administration.
AB  - Often medications that have to be administered to patients via a nasogastric
      enteral feeding tubes are only available as tablets and capsules with no suitable
      commercial liquid alternatives. In such situations, pharmacists and nurses have
      to compound the tablets and capsule contents into liquid suspension formulations
      for dosing. The risk of occlusion of the enteral tubes during administration is
      reduced by employing liquid suspensions that are composed of small and uniform
      particles, not subject to rapid rates of settling, resistant to caking, and
      easily and uniformly re-suspended upon agitation. Present techniques often employ
      a manual process, such as a mortar and pestle, to accomplish the particle size
      reduction and subsequent incorporation into a suitable liquid diluent. A new
      compounding device has been invented that employs an automated wet-milling
      process in a single-use disposable plastic container to compound the suspensions.
      The two processes were compared using Rifampin capsules and various liquid
      diluents. A prototype version of the new device was employed in the experiments.
      The physical characteristics of the compounded suspensions were evaluated by
      determining sedimentation rate, sedimentation volume, and particle size and shape
      using laser light scattering, optical microscopy, and scanning electron
      microscopy techniques. The use characteristic of the compounded suspensions was
      evaluated using a nasogastric tube inject ability test. The results indicated
      that suspensions prepared using the new device were more resistant to
      sedimentation and caking and were easier to re-disperse into a uniform mixture by
      gentle shaking. The results were a consequence of the particles generated by the
      new device which were found to be smaller and more uniform in shape and size. The
      suspensions prepared using the new device did not cause blockage of the enteral
      feeding tubes in comparison to those prepared using a mortar and pastle. In
      conclusion, the results indicate that the wet-milling process employed by the new
      compounding device produces liquid suspensions that are more suitable for dosing
      via nasogastric enteral tubes in comparison to the manual mortar and pestle
      method that is presently employed. 

PMID- 23965504
TI  - Weight uniformity of scored tablet halves manufactured by palestinian
      pharmaceutical companies.
AB  - The purpose of this study was to evaluate the weight uniformity of some commonly
      divided tablets produced by Palestinian Pharmaceutical companies. Volunteers were
      asked to divide scored tablets. The split units were individually weighed and the
      relative standard deviation for each product was calculated. Five scored tablet
      products failed the United States Pharmacopeia test of mass uniformity; this
      indicates that the splitting of these tablet products is not reliable for the
      provision of accurate doses. The practice of dividing tablets to achieve
      therapeutic and economic benefits for the patient may cause significant problems,
      especially in drugs with low therapeutic indices. Pharmacists may resolve this
      inconvenience by reformulating the tablet into a new dosage form, such as
      capsules, which should contain the exact amount of the medication. 

PMID- 23965505
TI  - Acute encephalitis syndrome surveillance, Kushinagar district, Uttar Pradesh,
      India, 2011-2012.
AB  - In India, quality surveillance for acute encephalitis syndrome (AES), including
      laboratory testing, is necessary for understanding the epidemiology and etiology
      of AES, planning interventions, and developing policy. We reviewed AES
      surveillance data for January 2011-June 2012 from Kushinagar District, Uttar
      Pradesh, India. Data were cleaned, incidence was determined, and demographic
      characteristics of cases and data quality were analyzed. A total of 812 AES case
      records were identified, of which 23% had illogical entries. AES incidence was
      highest among boys<6 years of age, and cases peaked during monsoon season.
      Records for laboratory results (available for Japanese encephalitis but not AES)
      and vaccination history were largely incomplete, so inferences about the
      epidemiology and etiology of AES could not be made. The low-quality AES/Japanese
      encephalitis surveillance data in this area provide little evidence to support
      development of prevention and control measures, estimate the effect of
      interventions, and avoid the waste of public health resources.

PMID- 23965507
TI  - When to order an antinuclear antibody test.

PMID- 23965508
TI  - Cranial ultrasonography of a term infant.

PMID- 23965506
TI  - Use of antidepressants near delivery and risk of postpartum hemorrhage: cohort
      study of low income women in the United States.
AB  - OBJECTIVE: To determine whether use of serotonin or non-serotonin reuptake
      inhibitors near to delivery is associated with postpartum hemorrhage. DESIGN:
      Cohort study. SETTING: 2000-07 nationwide Medicaid data (Medicaid Analytic
      eXtract). POPULATION: 106,000 pregnant women aged 12-55 with a diagnosis of mood
      or anxiety disorder. Women were categorized into four mutually exclusive exposure
      groups according to pharmacy dispensing data: current (delivery date), recent (1
      30 days before delivery date), past (1-5 months before delivery date), and no
      exposure (reference group). MAIN OUTCOME MEASURES: Risk of postpartum hemorrhage
      by timing of exposure and by serotonin or non-serotonin reuptake inhibitors,
      classes of antidepressant, and antidepressant types. Relative risks and 95%
      confidence intervals adjusted for delivery year, risk factors for postpartum
      hemorrhage, indicators of severity of mood/anxiety disorder, other indications
      for antidepressants, and other drugs. High dimensional propensity score (hdPS)
      methods were used to empirically identify and adjust for additional factors.
      RESULTS: 12,710 (12%) women had current exposure to serotonin reuptake inhibitor
      monotherapy, and 1495 (1.4%) women had current exposure to non-serotonin reuptake
      inhibitor monotherapy. The risk of postpartum hemorrhage was 2.8% among women
      with mood/anxiety disorders but no exposure to antidepressants, 4.0% in the
      current users of serotonin reuptake inhibitors, 3.8% in the current users of non
      serotonin reuptake inhibitors, 3.2% in the recent users of serotonin reuptake
      inhibitors, 3.1% in the recent users of non-serotonin reuptake inhibitors, 2.5%
      in the past users of serotonin reuptake inhibitors, and 3.4% in the past users of
      non-serotonin reuptake inhibitors. Compared with no exposure, women with current
      exposure to serotonin reuptake inhibitors had a 1.47-fold increased risk of
      postpartum hemorrhage (95% confidence interval 1.33 to 1.62) and women with
      current non-serotonin reuptake inhibitor exposure had a 1.39-fold increased risk
      (1.07 to 1.81). Results were similar with hdPS adjustment. Women with current
      exposure to serotonin reuptake inhibitors had an adjusted excess risk of 1.26%
      (0.90% to 1.62%), with a number needed to harm of 80, and for women with current
      exposure to non-serotonin reuptake inhibitors the excess risk was 1.03% (0.07% to
      1.99%), with a number needed to harm of 97. For exposure to serotonin reuptake
      inhibitors the relative risk was 1.19 (1.03 to 1.38) for recent exposure and 0.93
      (0.82 to 1.06) for past exposure; for non-serotonin reuptake inhibitors the
      figures were 1.17 (0.80 to 1.70) and 1.26 (1.00 to 1.59), respectively. Current
      exposure to selective serotonin reuptake inhibitor monotherapy was also
      associated with postpartum hemorrhage (1.42, 1.27 to 1.57), as was current
      serotonin norepinephrine (noradrenaline) reuptake inhibitor (1.90, 1.37 to 2.63)
      and tricyclic monotherapy (1.77, 0.90 to 3.47). All types of selective serotonin
      reuptake inhibitors available for analysis and venlafaxine, a serotonin
      norepinephrine reuptake inhibitor, were significantly associated with postpartum
      hemorrhage. CONCLUSIONS: Exposure to serotonin and non-serotonin reuptake
      inhibitors, including selective serotonin reuptake inhibitors, serotonin
      norepinephrine reuptake inhibitors, and tricyclics, close to the time of delivery
      was associated with a 1.4 to 1.9-fold increased risk for postpartum hemorrhage.
      While potential confounding by unmeasured factors cannot be ruled out, these
      findings suggest that patients treated with antidepressants during late pregnancy
      are more likely to experience postpartum hemorrhage.

PMID- 23965509
TI  - The NHS in the age of anxiety: rhetoric and reality--an essay by Rudolf Klein.

PMID- 23965510
TI  - HIV screening: helping clinicians make sense of test results to patients.

PMID- 23965511
TI  - Antidepressants and postpartum haemorrhage.

PMID- 23965512
TI  - CQC warns more providers over poor care standards.

PMID- 23965513
TI  - Simply wearing footwear could interrupt transmission of Strongyloides
      stercoralis.

PMID- 23965514
TI  - Expert panel will assess cost effectiveness of health checks.

PMID- 23965515
TI  - Provider choice and cost conscious consumers contribute to Singapore's
      performance.

PMID- 23965516
TI  - Equipping all citizens with the skills and equipment to be lifesavers.

PMID- 23965517
TI  - Ensuring a bright future for clinical research in surgery with trainee led
      research networks.

PMID- 23965518
TI  - The sulphydryl containing ACE inhibitor Zofenoprilat protects coronary
      endothelium from Doxorubicin-induced apoptosis.
AB  - Pediatric and adult cancer patients, following the use of the antitumor drug
      Doxorubicin develop cardiotoxicity. Pharmacological protection of microvascular
      endothelium might produce a double benefit: (i) reduction of myocardial toxicity
      (the primary target of Doxorubicin action) and (ii) maintenance of the vascular
      functionality for the adequate delivery of chemotherapeutics to tumor cells. This
      study was aimed to evaluate the mechanisms responsible of the protective effects
      of the angiotensin converting enzyme inhibitor (ACEI) Zofenoprilat against the
      toxic effects exerted by Doxorubicin on coronary microvascular endothelium. We
      found that exposure of endothelial cells to Doxorubicin (0.1-1MUM range) impaired
      cell survival by promoting their apoptosis. ERK1/2 related p53 activation, but
      not reactive oxygen species, was responsible for Doxorubicin induced caspase-3
      cleavage. P53 mediated-apoptosis and impairment of survival were reverted by
      treatment with Zofenoprilat. The previously described PI-3K/eNOS/endogenous
      fibroblast growth factor signaling was not involved in the protective effect,
      which, instead, could be ascribed to cystathionine gamma lyase dependent
      availability of H2S from Zofenoprilat. Furthermore, considering the tumor
      environment, the treatment of endothelial/tumor co-cultures with Zofenoprilat did
      not affect the antitumor efficacy of Doxorubicin. In conclusion the ACEI
      Zofenoprilat exerts a protective effect on Doxorubicin induced endothelial
      damage, without affecting its antitumor efficacy. Thus, sulfhydryl containing
      ACEI may be a useful therapy for Doxorubicin-induced cardiotoxicity. 

PMID- 23965519
TI  - Sugar-sensitive supramolecular structures based on phenylboronic Acid-modified
      cyclodextrins.
AB  - Supramolecular structures were developed from phenylboronic acid-modified
      cyclodextrins (PBA-CyDs). The intermolecular interaction between the PBA moiety
      and the CyD cavity was proved using two dimensional (2D)-NMR and powder X-ray
      diffraction techniques. PBA-alpha-CyD formed a head-to-tail supramolecular
      polymer, whereas PBA-beta-CyD formed a head-to-head dimer. The supramolecular
      structures were disintegrated in the presence of sugars owing to the resulting
      boronate sugar interactions. 

PMID- 23965520
TI  - Detection of diphtheritic polyneuropathy by acute flaccid paralysis surveillance,
      India.
AB  - Diphtheritic polyneuropathy is a vaccine-preventable illness caused by exotoxin
      producing strains of Corynebacterium diphtheriae. We present a retrospective
      convenience case series of 15 children (6 girls)<15 years of age (mean age 5.2
      years, case-fatality rate 53%, and 1 additional case-patient who was ventilator
      dependent at the time of last follow-up; median follow-up period 60 days) with
      signs and symptoms suggestive of diphtheritic polyneuropathy. All cases were
      identified through national acute flaccid paralysis surveillance, which was
      designed to detect poliomyelitis in India during 2002-2008. We also report data
      on detection of diphtheritic polyneuropathy compared with other causes of acute
      flaccid paralysis identified by this surveillance system.

PMID- 23965521
TI  - Antibody-mediated rejection, T cell-mediated rejection, and the injury-repair
      response: new insights from the Genome Canada studies of kidney transplant
      biopsies.
AB  - Prospective studies of unselected indication biopsies from kidney transplants,
      combining conventional assessment with molecular analysis, have created a new
      understanding of transplant disease states and their outcomes. A large-scale
      Genome Canada grant permitted us to use conventional and molecular phenotypes to
      create a new disease classification. T cell-mediated rejection (TCMR),
      characterized histologically or molecularly, has little effect on outcomes.
      Antibody-mediated rejection (ABMR) manifests as microcirculation lesions and
      transcript changes reflecting endothelial injury, interferon-gamma effects, and
      natural killer cells. ABMR is frequently C4d negative and has been greatly
      underestimated by conventional criteria. Indeed, ABMR, triggered in some cases by
      non-adherence, is the major disease causing failure. Progressive dysfunction is
      usually attributable to specific diseases, and pure calcineurin inhibitor
      toxicity rarely explains failure. The importance of ABMR argues against
      immunosuppressive drug minimization and stands as a barrier to tolerance
      induction. Microarrays also defined the transcripts induced by acute kidney
      injury (AKI), which correlate with reduced function, whereas histologic changes
      of acute tubular injury do not. AKI transcripts are induced in kidneys with late
      dysfunction, and are better predictors of failure than fibrosis and inflammation.
      Thus progression reflects ongoing parenchymal injury, usually from identifiable
      diseases such as ABMR, not destructive fibrosis. 

PMID- 23965523
TI  - In response.

PMID- 23965522
TI  - The renin-aldosterone axis in kidney transplant recipients and its association
      with allograft function and structure.
AB  - The level of the renin-angiotensin-aldosterone system (RAAS) activity in kidney
      transplant recipients has not been extensively studied or serially profiled. To
      describe this axis and to determine its association with glomerular filtration
      rate (GFR) change, interstitial expansion, and end-stage renal disease (ESRD), we
      measured plasma renin activity (PRA) and plasma aldosterone levels annually for 5
      years in 153 kidney transplant recipients randomly assigned to losartan or
      placebo. PRA and plasma aldosterone levels were in the normal range at all times
      and did not vary by immunosuppression regimen. Those on losartan exhibited higher
      PRA but similar plasma aldosterone levels. Neither baseline nor serial PRA or
      plasma aldosterone levels were associated with GFR decline, proteinuria, or
      interstitial expansion. Losartan use (hazard ratio (HR) 0.48 (95% confidence
      interval (CI) 0.21-1.0), insignificant) and Caucasian donor (HR 0.18 (95% CI 0.07
      0.4) significant) were associated with less doubling of serum creatinine, death,
      or ESRD. Hypertension, <3 human leukocyte antigen matches, the combination of
      tacrolimus-rapamycin, and acute rejection were associated with more events.
      Neither PRA nor plasma aldosterone levels were independently associated with this
      outcome. Higher serial plasma aldosterone levels were associated, however, with a
      significantly higher risk of ESRD (HR 1.01 (95% CI 1.00-1.02)). Thus, systemic
      RAAS is not overly activated in kidney transplant recipients, but this may not
      reflect the intrarenal system. Importantly, plasma aldosterone levels may be
      associated with more ESRD. 

PMID- 23965524
TI  - Aqueous humor oxygen measurements.

PMID- 23965525
TI  - Early adaptation and compensation of clinical vestibular responses after
      unilateral vestibular deafferentation surgery.
AB  - OBJECTIVE: To describe vestibulo-ocular function in the immediate postoperative
      period after unilateral vestibular deafferentation from vestibular schwannoma
      resection. STUDY DESIGN: Prospective longitudinal study. SETTING: Tertiary
      medical center. PATIENTS: Five patients who underwent vestibular schwannoma
      resection via retrosigmoid approach. INTERVENTIONS: Bedside video-oculography and
      video head impulse testing (HIT). MAIN OUTCOME MEASURES: Static and dynamic
      measures of vestibulo-ocular reflex (VOR) function including spontaneous
      nystagmus, skew deviation, VOR gain during HIT, and presence of saccades related
      to HIT. RESULTS: Mean ipsilesional horizontal VOR gain decreased from 0.88 +/-
      0.09 preoperatively to 0.27 +/- 0.20 on POD 2 (p = 0.004). Mean contralesional
      VOR gain declined from 0.95 +/- 0.1 preoperatively to 0.79 +/- 0.17 on POD 2 (p =
      0.032). By POD 4, ipsilesional VOR gain remained low, whereas contralesional VOR
      gain returned to baseline. Initially on POD 1 to 3, compensatory saccades
      occurred exclusively after the head stopped moving (overt) with latency of 192.8
      +/- 36.1 ms; by POD 5, saccade latency decreased to 134.5 +/- 23.5 ms (p =
      0.026), and saccades were occurring during the head rotation. Skew deviation was
      present and remained abnormal through POD 5 in 3 of the 5 patients. CONCLUSION:
      In the postoperative period, gaze stability seems to improve from contralesional
      VOR gain restoration and reduced latency of compensatory saccades.

PMID- 23965526
TI  - Dietary modification as adjunct treatment in Meniere's disease: patient
      willingness and ability to comply.
AB  - OBJECTIVE: To evaluate ease of use and compliance with dietary modification in
      the treatment of vertigo in patients with Meniere's disease. STUDY DESIGN: Mailed
      patient retrospective questionnaire and chart review. SETTING: Tertiary referral
      neurotologic private practice. SUBJECTS: 136 patients with Meniere's who returned
      a mailed questionnaire. Mean age at first clinic visit was 53 years, and at
      questionnaire was 62 years, with 54.4% female subjects. Median initial hearing
      was AAO-HNS Stage 1. Most patients also received diuretics and/or other
      treatments. INTERVENTION: Reduced sodium and caffeine-free diet. MAIN OUTCOME
      MEASURES: Ratings of diet difficulty, length of use, compliance level and
      nutritional understanding, and AAO-HNS vertigo class and functional rating before
      and with nutritional intervention. RESULTS: 46.3% of the respondents received
      written diet guidelines; only 3.2% were referred for nutritional counseling, and
      another 7.8% sought counseling independently. 77.8% and 84.7% rated a low sodium
      and a caffeine-free diet, respectively, as manageable or easy to follow; 77.9%
      followed the diet for 1 year or greater, but only 10.3% could list 5 "correct"
      foods to eat and 26% 5 foods to avoid. Those who followed the diet greater than 6
      months had larger improvement in number of spells and functional rating and a
      higher rate of Class A/B vertigo outcome (p <= 0.01, p = 0.012, and p = 0.038,
      respectively). Knowledge of foods to eat and avoid correlated with vertigo class
      (rho = -0.21, p <= 0.029 and rho = -0.26, p <= 0.01, respectively); the more
      foods correctly listed, the better the AAO-HNS class). CONCLUSION: Nutrition
      education by referral to a registered dietitian may improve outcomes in the
      medical treatment of Meniere's disease.

PMID- 23965527
TI  - Age-associated increase in arterial stiffness measured according to the cardio
      ankle vascular index without blood pressure changes in healthy adults.
AB  - AIM: The cardio-ankle vascular index (CAVI) reflects arterial stiffness from the
      aorta to the ankle, independent of blood pressure (BP). We investigated the age
      stratified CAVI in healthy, normotensive individuals to evaluate the effects of
      age on arterial stiffness. METHODS: The CAVI and peripheral BP were determined in
      healthy, normotensive Koreans 20 to 79 years of age. The subjects had no history
      of cardiovascular disease and did not take any medications for hypertension,
      diabetes mellitus or dyslipidemia (N = 1,380; 44.1% in men). RESULTS: The mean
      systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure
      (PP) were 117, 75 and 42 mmHg, respectively. The CAVI increased linearly with age
      and was determined using the following equation: CAVI = 5.0 + 0.048 * age (year)
      in men (r(2) = 0.395, p < 0.001), CAVI = 4.8 + 0.045 * age (year) in women (r(2)
      = 0.450, p < 0.001). However, SBP, DBP and PP did not change progressively with
      age. Age emerged as the major determinant of the CAVI in a stepwise multiple
      regression analysis (r(2) change = 43.1%). CONCLUSIONS: The CAVI scores increased
      with age in the healthy, normotensive individuals, whereas SBP, DBP and PP did
      not. Age was the dominant risk factor for the progression of arterial stiffness.
      These data suggest that the CAVI is a sensitive marker of the arterial aging
      process, above and beyond conventional upper arm BP.

PMID- 23965528
TI  - Nucleocytoplasmic shuttling of viral proteins in borna disease virus infection.
AB  - Nuclear import and export of viral RNA and proteins are critical to the
      replication cycle of viruses that replicate in the nucleus. Borna disease virus
      (BDV) is a nonsegmented, negative-strand RNA virus that belongs to the order
      Mononegavirales. BDV has several distinguishing features, one of the most
      striking being the site of its replication. BDV RNA is transcribed and replicated
      in the nucleus, while most other negative-strand RNA viruses replicate in the
      cytoplasm. Therefore, the nucleocytoplasmic trafficking of BDV macromolecules
      plays a key role in virus replication. Growing evidence indicates that several
      BDV proteins, including the nucleoprotein, phosphoprotein, protein X and large
      protein, contribute to the nucleocytoplasmic trafficking of BDV ribonucleoprotein
      (RNP). The directional control of BDV RNP trafficking is likely determined by the
      ratios of and interactions between the nuclear localization signals and nuclear
      export signals in the RNP. In this review, we present a comprehensive view of
      several unique mechanisms that BDV has developed to control its RNP trafficking
      and discuss the significance of BDV RNP trafficking in the replication cycle of
      BDV. 

PMID- 23965530
TI  - Gastroenteritis outbreak associated with unpasteurized tempeh, North Carolina,
      USA.
AB  - During an investigation of an outbreak of gastroenteritis caused by Salmonella
      enterica serovar Paratyphi B variant L(+) tartrate(+), we identified
      unpasteurized tempeh as a novel food vehicle and Rhizopus spp. starter culture as
      the source of the contamination. Safe handling of uncooked, unpasteurized tempeh
      should be emphasized for prevention of foodborne illnesses. 

PMID- 23965531
TI  - A facile solvothermal method to produce ZnS quantum dots-decorated graphene
      nanosheets with superior photoactivity.
AB  - Zinc sulfide-graphene (ZnS-GR) nanocomposites with a high degree of dispersion
      and high coverage of ZnS quantum dots (QDs) have been synthesized by a facile
      solvothermal method without any dispersant, during which the formation of ZnS
      nanoparticles and the reduction of graphene oxide (GO) occur simultaneously. ZnS
      GR nanocomposites exhibit much higher photoactivity than nanoparticle crystal ZnS
      (NPC-ZnS) prepared in the absence of graphene (GR), as evaluated by degradation
      of methylene blue (MB) in the liquid phase under ultraviolet (UV) light. Among
      them, the ZnS-GR nanocomposite with a 5% mass fraction of GR prepared at 120 
      degrees  C has the highest photocatalytic activity. The conversion and
      mineralization over MB are 96.7% and 57.1% respectively, which is much higher
      than that of NPC-ZnS. The high photoactivity of ZnS-GR nanocomposites can be
      ascribed to the integrated effect of an extremely high specific surface area and
      the excellent electron conductivity of GR and its significant influence on the
      morphology and structure of the samples. Moreover, it is found that the oxidation
      of MB is driven mainly by the participation of .OH radicals. Accordingly, a
      potential photocatalytic mechanism of ZnS-GR nanocomposites in the photocatalytic
      process has been proposed in this work. It is expected that our work could
      provide valuable information on the design of metal sulfide decorated GR with
      excellent properties.

PMID- 23965532
TI  - Prescription-beginning of a new United States pharmacopeial convention, inc.
      Cycle.

PMID- 23965529
TI  - Retroviral infections in sheep and goats: small ruminant lentiviruses and host
      interaction.
AB  - Small ruminant lentiviruses (SRLV) are members of the Retrovirus family
      comprising the closely related Visna/Maedi Virus (VMV) and the Caprine Arthritis
      Encephalitis Virus (CAEV), which infect sheep and goats. Both infect cells of the
      monocyte/macrophage lineage and cause lifelong infections. Infection by VMV and
      CAEV can lead to Visna/Maedi (VM) and Caprine Arthritis-Encephalitis (CAE)
      respectively, slow progressive inflammatory diseases primarily affecting the
      lungs, nervous system, joints and mammary glands. VM and CAE are distributed
      worldwide and develop over a period of months or years, always leading to the
      death of the host, with the consequent economic and welfare implications.
      Currently, the control of VM and CAE relies on the control of transmission and
      culling of infected animals. However, there is evidence that host genetics play
      an important role in determining Susceptibility/Resistance to SRLV infection and
      disease progression, but little work has been performed in small ruminants. More
      research is necessary to understand the host-SRLV interaction. 

PMID- 23965533
TI  - Developing an erythromycin ophthalmic ointment: putting the puzzle pieces
      together.
AB  - With the development of new treatment options and reported side effects with the
      use of silver nitrate ophthalmic solution, the drug manufacturers discontinued
      production of the silver nitrate ophthalmic solution in the mid-1990s. On
      December 9, 2009, the U.S. Food and Drug Administration announced that the
      erythromycin ophthalmic ointment 1-gram tubes were commercially available again
      and production by the manufacturer was expected to meet the historical demands.
      Hospitals could expect to replenish their inventory reserves after the first
      quarter of 2012. However, manufacturer backorders have been increasing due to a
      variety of factors. If a hospital has a compounding laboratory, it is possible to
      prepare erythromycin ophthalmic ointment according to the United States
      Pharmacopeia Chapter 797 standards. Since the commercial product has been
      available for decades without any major shortages until 2009, there isn't any
      published compounding information on how to prepare the ointment. This article
      discusses the development of a new procedure to compound erythromycin 0.5%
      ophthalmic ointment, the compound of which may be useful in any future shortages.
      Compounding can involve some intensive research in order to create a new
      formulation, especially when the compounder does not have access to a hired
      technical support service. It can be very challenging, but as this article
      explains, it is not impossible to do. 

PMID- 23965534
TI  - Recommendations for compounding medications for feeding tube administration.
AB  - There are no commercially available liquid medications that are formulated for
      feeding tube administration. The goal and indication of orally administered
      medications formulated in liquids is for pediatric patients or patients with
      limited ability to swallow tablets. Pharmacists who are considering compounding
      medications for feeding tube administration must be aware of the many issues
      involved in preparing drugs for this purpose. Many of these issues are discussed
      in this article. Also included in this article are reviews of some the literature
      involving the issues in co-administering nutrition by the same route. 

PMID- 23965535
TI  - Hygrometers and thermohygrometers: environmental monitoring ensures the potency
      and stability of compounding agents.
AB  - Although the terms humidity and relative humidity are often used interchangeably,
      they are not synonymous. Humidity is the amount of water in the air, and relative
      humidity is the ratio of the amount of water vapor in the air at a specific
      temperature to the maximum possible amount of water vapor in the air at that
      temperature. Thus humidity and temperature are inextricably bound in their
      effects on the environment. In a compounding pharmacy, humidity can affect the
      stability and quality of the compounds prepared, as well as equipment, chemicals,
      and polymers. Devices that measure relative humidity (hygrometers) or humidity
      and temperature (thermohygrometers) are essential instruments in a compounding
      pharmacy. They must be chosen carefully, however, to ensure that the measurements
      they yield are accurate, that they are reliable over time. Most desirable are
      devices that alert the pharmacist immediately at any time if levels of humidity
      or temperature at a designated site differ from a specific norm. In this report,
      we discuss the effects of humidity on the process of compounding and on the
      agents used in customized preparations. A Table that lists essential features of
      a variety of hygrometers and thermohygrometers appropriate for use in a
      compounding pharmacy is presented for easy reference. 

PMID- 23965536
TI  - Considerations for percutaneous absorption.
AB  - Percutaneous absorption is affected by numerous factors. Whether they are
      internal or external factors, the compounding pharmacist must collectively
      consider these variables in order to provide a safe and effective topical
      preparation for the patient. By considering the physiochemical and dermal factors
      that affect percutaneous absorption of a medication, an effective topical
      medication can be formulated to treat the patient's specific indication.
      Furthermore, this article will review the background information necessary to
      formulate transdermal prescriptions for their patients. 

PMID- 23965537
TI  - Thyroid potency calculations.
AB  - The United States Pharmacopeia defines the label strength for Levothyroxine
      Sodium USP, Liothyronine Sodium USP, and Thyroid Powder USP. These powders need a
      certificate of analysis for potency calculations. This article is an explanation
      of the calculations involved to achieve the correct United States Pharmacopeia
      label strength for thyroid hormones. 

PMID- 23965538
TI  - Unique challenges in compounding: managing severe musculoskeletal pain in a
      recovered substance abuser.
AB  - Compounding pharmacists can provide a great therapeutic service to pain
      management patients who have overcome an addiction to prescribed or illegal drugs
      or alcohol. By collaborating with the physician and the patient, the compounder
      can develop an effective analgesic formulation with no addictive potential; a
      preparation that can be safely adjusted to meet changing medical needs. In this
      report, we present a personal account of the value of two compounded preparations
      that relieve severe musculoskeletal pain without producing mood-altering effects,
      as well as information about how those compounds are prepared. 

PMID- 23965539
TI  - Quality-control analytical methods: pharmacopeial bacterial endotoxins test
      chapters.
AB  - This article summarizes and explains the essential provisions of the harmonized
      Bacterial Endotoxins Test chapter. The bacterial endotoxins test is an important
      requirement of United States Pharmacopeia Chapter 797, Pharmaceutical Compounding
      Sterile Preparations, which requires endotoxin testing of high-risk compounded
      sterile preparations. This article includes recommendations on endotoxin testing.

PMID- 23965540
TI  - Basics of compounding: basics of compounding with organic salts.
AB  - The purity and form of all ingredients used in compounding, especially of active
      pharmaceutical ingredients, must be known and considered during formulation. When
      a prescription is received, it is the responsibility of the pharmacist, and
      should be routine procedure, to correctly determine whether or not the salt or
      base/acid form of a drug is to be used as the basis for the dose. This is
      important information because the bulk substance, or active pharmaceutical
      ingredient, in a salt form is not 100% active drug. The purpose of the salt form
      is usually to enhance the solubility of the drug, but it may also enhance and
      change other attributes of the drug that make it easier to handle and manipulate
      for producing dosage forms. Resources for the purpose of determining this
      information include the United States Pharmacopeia, product package insert, and a
      call to the manufacturer or physician as appropriate. This article discusses
      compounding with salts and the factors that may affect a final compounded
      preparation. 

PMID- 23965541
TI  - Basics of compounding: considerations for implementing United States pharmacopeia
      chapter 797 pharmaceutical compounding-sterile preparations, part 20: patient or
      caregiver training, patient monitoring and adverse events reporting, and quality
      assurance program.
AB  - This article is intended to address the activities of the caregiver and encourage
      the need to address adverse events or medical errors. The advantage of disclosing
      adverse events or medication errors is to avoid further potential errors and
      determine/correct the cause of the errors. There should be awareness between
      patients and caregivers on the proper use and administration of intended
      compounded sterile preparations. Patients/patient's relatives should ask
      questions about their medications and be knowledgeable or cognizant on the
      appearance of the preparation or specified dosage of the medication. Caregivers
      should be open and explicit about the medications being administered or
      prescribed by the doctor and the rationale for such medications. This module will
      address these sections in a practical manner and provide practice clarification
      to the standards. 

PMID- 23965542
TI  - Evaluation of extemporaneous oral itraconazole suspensions by dissolution
      profiles mapping.
AB  - The objective of this study was to evaluate by dissolution profiles mapping five
      extemporaneous oral itraconazole suspensions reported in the literature.
      Dissolution profiles of the extemporaneous oral itraconazole preparations were
      mapped and correlated with their reported clinical data therein. Four out of five
      extemporaneous preparations had either too early or insufficient release of
      itraconazole during the dissolution study, potentially limiting the in vivo oral
      bioavailability in patients. Dissolution profiles in the remaining extemporaneous
      preparation was closely similar to that in commercial itraconazole capsules.
      Based on the reported clinical data and dissolution results in this study, the
      extemporaneous preparation proposed in a study by Ong and Fobes seems to be the
      most reasonable choice for our patients. Dissolution profile evaluation is an
      important quality-control parameter during the evaluation of extemporaneous
      preparations by pharmacists. 

PMID- 23965543
TI  - Compatibility and stability of cefotaxime, vancomycin, and ciprofloxacin in
      antibiotic lock solutions containing heparin.
AB  - The purpose of this study was to assess the compatibility and stability of drugs
      commonly found in antibiotic lock solutions (cefotaxime 10 mg/mL plus heparin
      5000 IU/mL, vancomycin 25 mcg/mL plus heparin 10 IU/mL, and vancomycin 25 mcg/mL
      plus ciprofloxacin 2 mg/mL plus heparin 10 IU/mL). Antibiotic lock solutions
      under investigation were generated in triplicate from pooled starting samples and
      maintained at 4 degrees Celsius, 27 degrees Celsius, and 40 degrees Celsius. The
      antibiotic lock solutions were assessed at various time intervals for chemical
      stability (specified as retaining greater than 90% of initial drug via high
      performance liquid chromatographic analysis) and physical stability(specified as
      solution free of visible precipitates). Antibiotic lock solutions containing
      cefotaxime plus heparin remained chemically and physically stable at 4 degrees
      Celsius throughout the study period. However, samples maintained at higher
      temperatures had no physical instability but underwent significant chemical
      degradation as early as 24 hours after the beginning of the incubation period.
      Vancomycin in antibiotic lock solutions with heparin also remained chemically and
      physically stable at 4 degrees Celsius but underwent minor chemical degradation
      (with no physical instability) at higher temperatures. Vancomycin and
      ciprofloxacin in antibiotic lock solutions with heparin demonstrated physical
      instability at all temperatures by 24 hours. In conclusion, none of the
      antibiotic lock solutions tested met the chemical and physical stability criteria
      specified at the beginning of the study. These results suggest that the efficacy
      of these antibiotic lock solutions is decreased due to chemical or physical
      instabilities over time. 

PMID- 23965544
TI  - Simultaneous early ovarian and endometrial cancer treated conservatively with
      spontaneous pregnancy.
AB  - INTRODUCTION: Young cancer patients increasingly request fertility sparing
      alternatives to their cancer treatments, which they should be offered when
      allowed so by the risk-benefit balance and after obtaining informed consent. CASE
      PRESENTATION: Here, we report the case of a 25 year-old nulliparous patient who
      presented with a synchronous endometrioid ovarian and endometrial carcinoma. She
      was able to conduct a full-term spontaneous pregnancy after conservative surgical
      treatment followed by adjuvant chemotherapy and hormonal treatment. Fertility
      sparing treatment is feasible in selected cases of synchronous ovarian and
      endometrial cancers. Thorough follow-up remains mandatory. CONCLUSION: This case
      demonstrates some interesting and unique features of synchronous ovarian and
      endometrial cancers since it resulted in a spontaneous pregnancy and normal
      delivery.

PMID- 23965545
TI  - Allergic contact dermatitis due to ginkgo tree fruit and leaf.

PMID- 23965546
TI  - Decrease of ATP by mitochondrial m-calpain inhibitory peptide in the rat retinas.
AB  - Activations of mitochondrial calpains cause apoptosis-inducing factor-dependent
      apoptosis of retinal photoreceptor cells in the Royal College of Surgeons (RCS)
      rat, an animal model of retinitis pigmentosa. In the present study, we attempted
      to develop specific inhibitors of mitochondrial calpains that would prevent the
      retinal degeneration. We examined the inhibitory potency of 20-mer peptides of
      the m-calpain for mitochondrial calpains activity, determined the inhibitory
      regions, and conjugated the cell-penetrating peptides (CPP). The cytotoxicity and
      delivery of the peptide was evaluated using mouse photoreceptor-derived 661W
      cells. After intravitreal injection of the peptide in RCS rats, we examined the
      peptide delivery to the retina, photoreceptor cell death numbers, responses of
      the electroretinogram (ERG), concentrations of intracellular ATP, and changes of
      retinal morphology. Results showed that one of the peptides inhibited the
      activity of the mitochondrial m-calpain. The HIV-1 tat-conjugated m-calpain
      peptide, HIV-Nm, could preserve the inhibitory potency of the mitochondrial m
      calpain, and penetrate into the 661W cells. While intravitreal injection of HIV
      Nm made it possible to deliver to the retina, it did not prevent photoreceptor
      cell death. Furthermore, it caused the ERG attenuation and the decrease in the
      intracellular ATP only a day after the injection. Although HIV-Nm did not cause
      histological change of the retina after 1 or 2 days of the administration, the
      morphological abnormality of the retina was observed after 3-14 days. Our results
      demonstrated that HIV-Nm failed to prevent the photoreceptor cell death, but
      rather caused the attenuation of ERG response and the decrease of ATP. 

PMID- 23965547
TI  - Sample size formulae for the Bayesian continual reassessment method.
AB  - BACKGROUND: In the planning of a dose finding study, a primary design objective
      is to maintain high accuracy in terms of the probability of selecting the maximum
      tolerated dose. While numerous dose finding methods have been proposed in the
      literature, concrete guidance on sample size determination is lacking. PURPOSE:
      With a motivation to provide quick and easy calculations during trial planning,
      we present closed form formulae for sample size determination associated with the
      use of the Bayesian continual reassessment method (CRM). METHODS: We examine the
      sampling distribution of a nonparametric optimal design and exploit it as a proxy
      to empirically derive an accuracy index of the CRM using linear regression.
      RESULTS: We apply the formulae to determine the sample size of a phase I trial of
      PTEN-long in pancreatic cancer patients and demonstrate that the formulae give
      results very similar to simulation. The formulae are implemented by an R function
      'getn' in the package 'dfcrm'. LIMITATIONS: The results are developed for the
      Bayesian CRM and should be validated by simulation when used for other dose
      finding methods. CONCLUSIONS: The analytical formulae we propose give quick and
      accurate approximation of the required sample size for the CRM. The approach used
      to derive the formulae can be applied to obtain sample size formulae for other
      dose finding methods.

PMID- 23965549
TI  - Renal vasodilating capacity and endothelial function are impaired in patients
      with obstructive sleep apnea syndrome and no traditional cardiovascular risk
      factors.
AB  - OBJECTIVE: Patients with obstructive sleep apnea syndrome exhibit accelerated
      vascular aging and renal damage. Aim of the study was to investigate whether
      vascular dysfunction is a feature of obstructive sleep apnea syndrome per se or
      instead related to the presence of traditional cardiovascular risk factors.
      METHODS: Forty patients with moderate-severe obstructive sleep apnea syndrome (20
      with, 20 without traditional risk factors) and 20 matched healthy controls were
      enrolled. Renal vasodilating capacity, endothelium-dependent vasodilation in the
      brachial artery, carotid-femoral pulse wave velocity and carotid stiffness were
      measured. Oxidative stress, endothelial biomarkers and leukocyte adhesion
      molecule levels were also evaluated. RESULTS: Apneic patients without traditional
      cardiovascular risk factors presented reduced endothelium-dependent vasodilation
      (3.7+/-2.1 versus 6.1+/-3.0%, P<0.05), increased serum E-selectin (49.8+/-11.5
      versus 38.9+/-17.9 ng/ml, P<0.05), and impaired renal vasodilating capacity
      (6.0+/-4.3 versus 10.4+/-6.1%, P<0.05), as compared to healthy controls.
      Endothelial NO synthase expression was reduced (0.0133 versus 0.0221*10
      copies/MUg RNA, P<0.05), whereas oxidative stress parameters and leukocyte
      adhesion molecules were similar to controls. Patients with obstructive sleep
      apnea syndrome and traditional risk factors also exhibit increased aortic and
      carotid stiffness, increased renal resistive index and intima-media thickness,
      and reduced expression of the endothelial progenitor cell marker CD34: however,
      these parameters were similar to those of healthy controls in patients with
      isolated obstructive sleep apnea syndrome. CONCLUSION: Obstructive sleep apnea
      syndrome is characterized by endothelial dysfunction and activation and impaired
      renal vasodilating capacity even in the absence of traditional cardiovascular
      risk factors, possibly due to reduced endothelial NO synthase expression.

PMID- 23965548
TI  - Nodding syndrome.
AB  - An epidemic illness characterized by head nodding associated with onchocerciasis
      has been described in eastern Africa since the early 1960s; we summarize
      published reports and recent studies. Onset of nodding occurs in previously
      healthy 5-15-year-old children and is often triggered by eating or cold
      temperatures and accompanied by cognitive impairment. Its incidence has increased
      in Uganda and South Sudan over the past 10 years. Four case-control studies
      identified modest and inconsistent associations. There were nonspecific lesions
      seen by magnetic resonance imaging, no cerebrospinal fluid inflammation, and
      markedly abnormal electroencephalography results. Nodding episodes are atonic
      seizures. Testing has failed to demonstrate associations with trypanosomiasis,
      cysticercosis, loiasis, lymphatic filariasis, cerebral malaria, measles, prion
      disease, or novel pathogens; or deficiencies of folate, cobalamin, pyridoxine,
      retinol, or zinc; or toxicity from mercury, copper, or homocysteine. There is a
      consistent enigmatic association with onchocerciasis detected by skin snip or
      serologic analysis. Nodding syndrome is an unexplained epidemic epilepsy. 

PMID- 23965551
TI  - Cholesterol key in Rett syndrome.

PMID- 23965552
TI  - Taking the bite out of TMJD pain.

PMID- 23965554
TI  - Diabetes drug could lead to longer life.

PMID- 23965555
TI  - New models for studying hepatitis C.

PMID- 23965557
TI  - Taking the temperature of the painted turtle.

PMID- 23965558
TI  - Using research animals as sentinels.

PMID- 23965559
TI  - Response to protocol review scenario: consider the purpose.

PMID- 23965560
TI  - Response to protocol review scenario: a word from OLAW and USDA.

PMID- 23965561
TI  - Response to protocol review scenario: approval required, methods may vary.

PMID- 23965562
TI  - Response to protocol review scenario: foster a team mentality.

PMID- 23965564
TI  - A thigmotaxis-based method of recapturing and transporting small mammals in the
      laboratory.
AB  - One of the challenges associated with breeding and testing of wild animals in the
      laboratory is their drive to escape. Wild rats attempt to escape their cages as
      soon as they are opened, and recapturing is often difficult and dangerous to
      laboratory personnel. The authors describe a method of recapturing wild small
      mammals in a laboratory setting that takes advantage of thigmotaxis, or the
      natural tendency to move close to walls and other solid objects. They describe a
      simple device that is easy to construct and can be used to recapture escaped rats
      and return them to their home cages. The recapture technique is efficient and
      benefits animals' well-being by minimizing their distress. 

PMID- 23965565
TI  - Regulatory requirements for providing adequate veterinary care to research
      animals.
AB  - Provision of adequate veterinary care is a required component of animal care and
      use programs in the United States. Program participants other than veterinarians,
      including non-medically trained research personnel and technicians, also provide
      veterinary care to animals, and administrators are responsible for assuring
      compliance with federal mandates regarding adequate veterinary care. All program
      participants therefore should understand the regulatory requirements for
      providing such care. The author provides a training primer on the US regulatory
      requirements for the provision of veterinary care to research animals.
      Understanding the legal basis and conditions of a program of veterinary care will
      help program participants to meet the requirements advanced in the laws and
      policies. 

PMID- 23965566
TI  - Best practices for IACUCs in the evaluation of multiple major operative
      procedures.
AB  - Evaluation of multiple major operative procedures can be a daunting task for
      IACUCs. Committee members need to know what a major operative procedure is, when
      multiple major operative procedures are permitted under the Animal Welfare Act,
      when permission from the Administrator of the US Department of Agriculture's
      Animal and Plant Health Inspection Service is required for multiple major
      operative procedures, and what information must be included when requesting such
      permission. The author discusses the intent and requirements for multiple major
      operative procedures under the Animal Welfare Act and describes best practices
      that IACUCs may use in evaluating multiple major operative procedures both within
      and across protocols. 

PMID- 23965567
TI  - Training initiatives for non-native English speakers in laboratory animal care.

PMID- 23965568
TI  - Faith versus science.

PMID- 23965569
TI  - Supporting research as well as compliance.

PMID- 23965570
TI  - Spatial processing: Humans are on the grid.

PMID- 23965572
TI  - Viewpoint on "Dissolvable fluidic time delays for programming multi-step assays
      in instrument-free paper diagnostics".

PMID- 23965574
TI  - Exploring the speed limits of liquid chromatography using shear-driven flows
      through 45 and 85 nm deep nano-channels.
AB  - We explored the possibility to perform high speed and high efficiency liquid
      chromatographic separations in channels with a sub-100 nm depth. The mobile phase
      flow through these nano-channels was generated using the shear-driven flow
      principle to generate high speed flows which were the equivalent of a 12,000 bar
      pressure-driven flow. It was found that the ultra-fast mass transfer kinetics
      prevailing in this range of small channel depths allow to drastically reduce the
      C-term contribution to band broadening, at least up to the upper speed limit of
      our current set-up (7 mm s(-1) mobile phase velocity), leaving the inescapable
      molecular diffusion (i.e., B-term band broadening) as the sole detectable source
      of band broadening. Due to the greatly reduced mass transfer limitations, 50,000
      to 100,000 theoretical plates could be generated in the span of 1 to 1.5 seconds.
      This is nearly two orders of magnitude faster than the best performing commercial
      pressure-driven UHPLC-systems. With the employed channel depths, we appear to
      have struck a practical lower limit for the channel miniaturization of shear
      driven flows. Despite the use of channel substrates with the highest grades of
      optical flatness, the overall substrate waviness (on the order of some 5 to 10
      nm) can no longer be neglected compared to the etched channel depth, which in
      turn significantly influenced the local retention factor and band broadening.

PMID- 23965573
TI  - West Nile virus RNA in tissues from donor associated with transmission to organ
      transplant recipients.
AB  - We identified West Nile virus (WNV) RNA in skin, fat, muscle, tendon, and bone
      marrow from a deceased donor associated with WNV transmission through solid organ
      transplantation. WNV could not be cultured from the RNA-positive tissues. Further
      studies are needed to determine if WNV can be transmitted from postmortem
      tissues. 

PMID- 23965575
TI  - Anisotropic growth of NiO nanorods from Ni nanoparticles by rapid thermal
      oxidation.
AB  - NiO nanorods with extremely high crystallinity were grown by rapid thermal
      oxidation through exposure of Ni nanoparticles (NPs) heated above 400 degrees  C
      to oxygen. Oxidation proceeds by nucleation of a NiO island on a Ni NP that grows
      anisotropically to produce a NiO nanorod. This process differs completely from
      that under mild oxidation conditions, where the surface of the NPs is completely
      covered with an oxide film during the early stage of oxidation. The observed
      novel behaviour strongly suggests an interfacial oxidation mechanism driven by
      the dissolution of adsorbed oxygen into the Ni NP sub-surface region, subsequent
      diffusion and reaction at the NiO/Ni interface. The early oxidation conditions of
      metal NPs impose a significant influence on the entire oxidation process at the
      nanoscale and are therefore inherently important for the precise morphological
      control of oxidized NPs to design functional nanomaterials.

PMID- 23965576
TI  - Epithelioid hemangioendothelioma of the liver: the role of hepatobiliary phase
      imaging for the preoperative diagnosis and qualification of patients for liver
      transplantation -- preliminary experience.
AB  - BACKGROUND: The aim of this study was to determine if the appearance of hepatic
      epithelioid hemangioendothelioma (HEHE) on state-of-the-art MRI including
      hepatocyte phase after administration of hepatobiliary contrast agent can
      facilitate preoperative diagnosis and identification of potential candidates for
      liver transplantation. MATERIAL AND METHODS: The study group comprised 6 patients
      with pathologically confirmed HEHE. Analysis included signal characteristics of
      55 tumor nodules (maximum of 10 lesions per patient) on T2-weighted images,
      dynamic contrast-enhanced, 5-minute delayed, and hepatobiliary phase images.
      RESULTS: The most common feature of HEHE, observed in 84% of lesions, was
      progressive contrast-enhancement, followed by subcapsular location (66%),
      confluent appearance (60%) and hyper- or isointensity on hepatobiliary phase
      images (53%). In 5 of 6 patients, capsular retraction was observed. CONCLUSIONS:
      The appearance of HEHE on hepatobiliary phase images was variable, but examined
      tumors often demonstrated hyper- or isointensity, most probably due to prolonged
      retention of contrast material. These features, along with typical morphology
      (subcapsular, confluent nodules, with progressive enhancement and capsular
      retraction), may contribute to correct diagnosis and recognition of potential
      candidates for liver transplantation.

PMID- 23965577
TI  - Prescription.

PMID- 23965578
TI  - Home infusion accreditation: another quality recognition branding tool.
AB  - Accreditation plays a significant role in fostering public confidence in the
      healthcare organization, enhancing organizational effectiveness, and improving
      patient care. It also provides the basis on which referral sources and payers can
      be assured that accredited organizations have complied with a common set of
      requirements and standards. Accreditation is the only comprehensive measure of a
      home infusion company's performance. The objective of this article is to provide
      information to help streamline and simplify the accreditation process and lower
      implementation times and associated costs. 

PMID- 23965579
TI  - Community pharmacy addresses the need for proper drug disposal with positive
      response.
AB  - In response to growing concerns regarding the improper disposal of prescription
      and over-the-counter drugs and its impact on the environment and teen drug abuse,
      the National Community Pharmacists Association developed a Prescription Disposal
      Program to assist its members in voluntarily developing consumer disposal options
      in their stores. The program includes a discount on products from partner
      organization Sharps Compliance Inc., free marketing materials, and national
      promotion via a new consumer website. To date, the program has nearly 1,000
      community pharmacies in 47 states participating. A collection of 8,000 pounds of
      drugs has resulted, with more campaigns slated for the future. Included with this
      article are testimonials from compounding pharmacists who have initiated National
      Community Pharmacists Association's drug disposal program. 

PMID- 23965580
TI  - Implementation of a viable air-sampling program using a volumetric collection
      device.
AB  - Implementation of the United States Pharmacopeia Chapter 7797 viable air sampling
      process can be done via various methods. This multi-site infusion pharmacy
      organization considered several factors in developing an air-sampling program.
      This article reviews the factors that should be considered, challenges of
      implementation, and results of deciding to conduct in-house testing. 

PMID- 23965581
TI  - Bioidentical hormones in the news.
AB  - This article reviews a collection of recent articles and published studies on sex
      hormone replacement therapy with the use of endogenous human hormones including
      estradiol, estriol, progesterone, and testosterone. 

PMID- 23965582
TI  - Conservative management of chronic kidney disease in cats: recommendations for
      veterinarians and compounding pharmacists.
AB  - Chronic kidney disease is a major cause of morbidity and mortality in aging cats,
      and assessment of that condition suggest that conservative management can provide
      substantial benefit for patients. The veterinarian's armamentarium is augmented
      each year with effective therapies for treating renal disease that are designed
      for human patients but can be successfully adapted for use in cats. The help of
      an experienced compounding pharmacist is invaluable in converting many of those
      treatments to the doses and dosage forms appropriate for veterinary patients. In
      this report, we examine effective approaches to the conservative treatment of
      chronic kidney disease in cats. Formulations useful in relieving the signs and
      symptoms of that disorder and in improving both adherence and the patient's
      quality of life are made available. 

PMID- 23965583
TI  - Tetracaine lollipops for the suppression of extreme gag reflex in dental
      patients.
AB  - An extreme gag reflex renders prophylactic dental care and undergoing operative
      dental procedures impossible for many people. Commercially available oral spray
      and lozenge anesthetics have an unpleasant taste and provide an insufficient
      duration of anesthesia. Compounded flavored tetracaine lollipops are an excellent
      alternative to other oral anesthetics and have enabled the treatment of many
      patients who have a strong aversion to dental care. In this report, we describe
      the use of the preparation in such patients. A formulation for tetracaine
      lollipops 0.5% is included. 

PMID- 23965584
TI  - Development of a standardized intranet database of formulation records for
      nonsterile compounding, part 1.
AB  - New methods for reducing medication errors in sterile compounds are always being
      considered, but the safety and stability of nonsterile compounded formulations
      are often overlooked in both hospital and independent compounding pharmacies.
      Extemporaneous compounding benefits from the pharmacist's easy access to a
      comprehensive computerized database that is based on high-performance liquid
      chromatography research and can be incorporated into a pharmacy information
      system to standardize formulations and prevent errors (which in turn improves
      patient safety). The Mission Health System, which is based in Asheville, North
      Carolina, is the cornerstone of advanced medical care in western North Carolina.
      Hospital providers in that healthcare system occasionally require customized
      compounded formulations to meet the needs of their patients (in particular,
      pediatric patients). However, each satellite pharmacy in the Mission Hospital
      system has a specific set of formulation records, and no standardized format for
      those records exists. In addition, beyond-use dates in many of those formulations
      either do not exist or are not referenced. The objectives of this project were to
      standardize the format of formulation records, create a computerized system so
      that all hospital pharmacists would have access to the same formulation records,
      create a computerized system so that all hospital pharmacists would have access
      to the same formulations, establish beyond-use dates (for nonsterile
      preparations) based on published stability studies or the most current tertiary
      literature, and improve the quality-control process for extemporaneously
      compounded nonsterile formulations prepared at the satellite hospital
      preparations and if standardized formulations are rendered easily accessible,
      then the potential for medication errors will be reduced and patient safety will
      improve. 

PMID- 23965585
TI  - Quality-control analytical methods: endtoxins: essential testing for pyrogens in
      the compounding laboratory, part 1.
AB  - Inadvertent exposure to endotoxins administered intravenously, intramuscularly,
      or intrathecally can cause a constellation of adverse effects that range from
      fever to multiple organ failure and death. Pharmacists who compound sterile
      formulations must remain exceptionally vigilant to guard against the
      contamination of such preparations with those pyrogens. Fortunately, endotoxin
      screening analyses are available for onsite use or from contract testing
      laboratories, and both options offer accurate, repeatable, and timely results.
      The volume of sterile compounding performed, the need for immediate results, and
      cost often dictate the compounder's choice of endotoxin testing. In this first of
      a 3-part series, we summarize the evolution of pyrogen screening and explain the
      mechanisms of two endotoxin test kits that provide valid results on site. A Table
      comparing those kits is presented for easy reference. In part 2 of the series,
      additional endotoxin test kits will be compared, and contract laboratory pyrogen
      testing will be profiled. In part 3, a simplified endotoxin test method for
      compounded sterile products will be presented. 

PMID- 23965586
TI  - Basics of compounding: basics of compounding with esters.
AB  - Pharmacists involved in compounding must consider a number of factors when
      determining the actual quantity of an active ingredient to use for a compounded
      prescription. Is the drug being dosed as its base form or as a salt, ester, etc.?
      Since the bulk substance, or active pharmaceutical ingredient, is not 100% active
      drug in all cases, then it is important to know whether or not the dose of the
      drug is based upon the drug ester or drug base form. This article discusses the
      basics of compounding with those drugs that are esters by the addition of a
      moiety that will form an aster for certain purposes. 

PMID- 23965588
TI  - Stability and compatibility of reconstituted caspofungin in select elastomeric
      infusion devices.
AB  - The stability and compatibility of caspofungin acetate reconstituted in 0.9%
      sodium chloride injection was studied in select elastomeric infusion devices.
      Caspofungin acetate solutions at three different concentrations, 0.2, 0.28, and
      0.5 mg/mL, were stored in three commonly used elastomeric infusion devices at 5
      degrees Celsius +/- 3 degrees Celsius and at room temperature. Sample mixtures of
      the drug were tested for stability every 12 hours (60 hours maximum) at room
      temperature, every 24 hours (72 hours maximum), and at 8, 9, and 14 days under
      refrigerated conditions (5 degrees Celsius +/- 3 degrees Celsius). Samples were
      assayed by using a high-performance liquid chromatographic method. The
      reconstituted caspofungin solutions maintained (greater than or equal to 90%) of
      the original active concentration for the duration of this study under both
      storage conditions. Degradation product levels remained within historical limits
      throughout the course of this study. Furthermore, the initial concentration of
      the caspofungin solutions was found to have no effect on the study results. 

PMID- 23965587
TI  - Quality control and physical and chemical stability of hydrocortisone oral
      suspension: an interlaboratory study.
AB  - There were two objectives of this study, one of which was to ensure that
      different 1-mg/mL hydrocortisone oral suspensions that were prepared as
      compounded preparations in four accredited laboratories using the same standard
      operating procedure were in accordance with the general quality controls of these
      disperse systems and the specific requirements of the European Pharmacopeia, the
      Royal Spanish Pharmacopeia, and the United States Pharmacopeia. The other
      objective was to confirm the shelf-life of 90 days that was established for this
      type of compounded preparation. All the suspensions were in accordance with the
      organoleptic controls and with the theoretically calculated volume per unit of
      the preparation, but the amount of active ingredient per volume of the
      preparations were smaller than the theoretically expected. This result was
      attributed to the standard operating procedure because no significative
      differences between laboratories and days were detected, in which an excess of
      active ingredient is necessary to include in the process to ensure the declared
      dose. By high-performance liquid chromatography, it was possible to confirm the
      90 days of stability of the drug at 5 degrees Celsius. 

PMID- 23965590
TI  - The CUSUM analysis of the learning curve for endoscopic thyroidectomy by the
      breast approach.
AB  - OBJECTIVES: To evaluate the learning curve for endoscopic thyroidectomy by the
      breast approach (ETBBA) based on the cumulative summation (CUSUM) technique.
      METHODS: The study included 110 consecutive patients who underwent ETBBA by a
      single surgeon between January 2009 and May 2012 at the Xiangya Hospital of
      Central South University, Changsha, China. The learning curve was evaluated using
      the CUSUM technique. The patients were chronologically arranged into 3 phases by
      the CUSUM analysis for operative time. Demographic data and operative parameters
      were also analyzed. RESULTS: The mean operative time (OT) was 125.3 minutes. The
      conversion rate for technical difficulties and the definitive complication rate
      were 6.4% and 10%, respectively. The learning curve was analyzed mainly by OT
      using the CUSUM technique. There was a significant improvement in the average OT
      (P < .05) after the first 27 patients and again after the first 67 patients (P <
      .05). A downward trend in OT was found up to the last patient. There were
      similarities in gender, tumor size, extent of surgery, blood loss, histology,
      hospital stay, conversion rate, and complications among the 3 phases. Comparison
      of 2 neighboring phases also showed no significant differences in age.
      CONCLUSIONS: ETBBA performed by surgeons has a remarkable learning curve. There
      were 27 cases in the early stage of the learning curve, whereas mastery level
      could be achieved with 67 cases.

PMID- 23965589
TI  - Five-year mortality after acute poisoning treated in ambulances, an emergency
      outpatient clinic and hospitals in Oslo.
AB  - BACKGROUND: The long-term mortality after prehospital treatment for acute
      poisoning has not been studied previously. Thus, we aimed to estimate the five
      year mortality and examine the causes of death and predictors of death for all
      acutely poisoned patients treated in ambulances, the emergency outpatient clinic,
      and hospitals in Oslo during 2003-2004. METHODS: A prospective cohort study
      included all adults (>=16 years; n=2045, median age=35 years, male=58%) who were
      discharged after treatment for acute poisoning in ambulances, the emergency
      outpatient clinic, and the four hospitals in Oslo during one year. The patients
      were observed until the end of 2008. Standardized mortality rates (SMRs) were
      calculated and multivariate Cox regression analysis was applied. RESULTS: The
      study comprised 2045 patients; 686 treated in ambulances, 646 treated in the
      outpatient clinic, and 713 treated in hospitals. After five years, 285 (14%)
      patients had died (four within one week). The SMRs after ambulance, outpatient,
      and hospital treatment were 12 (CI 9-14), 10 (CI 8-12), and 6 (CI 5-7),
      respectively. The overall SMR was 9 (CI 8-10), while the SMR after opioid
      poisoning was 27 (CI 21-32). The most frequent cause of death was accidents
      (38%). In the regression analysis, opioids as the main toxic agents (HR 2.3, CI
      1.6-3.0), older age (HR 1.6, CI 1.5-1.7), and male sex (HR 1.4, CI 1.1-1.9)
      predicted death, whereas the treatment level did not predict death. CONCLUSIONS:
      The patients had high mortality compared with the general population. Those
      treated in hospital had the lowest mortality. Opioids were the major predictor of
      death.

PMID- 23965591
TI  - The role of intraoperative nerve monitoring (IONM) in thyroidectomy: where do we
      stand today?
AB  - OBJECTIVE: Intraoperative nerve monitoring (IONM) gains daily ground, being used
      during thyroidectomy to help the surgeon identify the recurrent laryngeal nerve
      (RLN). But its value still remains debatable among endocrine surgeons. In this
      review article, we aim to present current knowledge on the subject. DATA SOURCES:
      The MEDLINE/PubMed database was searched for publications with the medical
      subject heading "Intraoperative Nerve Monitoring (IONM)" and keywords
      "thyroidectomy," "recurrent laryngeal nerve (RLN)" or "vocal cord paresis or
      vocal cord paralysis (VCP)." The search was conducted both on basis of the MESH
      tree and as a text search. STUDY SELECTION/DATA EXTRACTION: We restricted our
      search to English till July 2012. In this review, we only included 34 articles
      and abstracts that were available in English. CONCLUSIONS: RLN IONM adds a
      functional dimension to surgery that aids, but does not replace, visual
      identification. For the time being, intraoperative visual identification of the
      nerve and preoperative and postoperative laryngoscopic assessment of vocal cord
      function remain the gold standard of RLN management in thyroid surgery. Whether
      IONM will become a standard of care or not depends on the familiarization of each
      surgeon with this technique as well as on the publication of studies involving
      large series of thyroidectomies, where the evaluation of IONM will have
      significant statistical power.

PMID- 23965592
TI  - Alternative conduits for microvascular anastomoses.
AB  - Thrombotic events in vascular substitutes are the main cause of obliteration of
      most microvascular prostheses and subsequent failure of microvascular
      anastomoses. The development of new biomaterials for vascular replacement aims to
      obtain an ideal graft for microvascular surgery. Completely bioresorbable
      vascular prostheses with the capacity to induce regeneration and growth of a new
      vascular segment seem to overcome the limitations of contemporary artificial
      prostheses, mostly made of artificial materials and lacking the capacity to grow
      and be remodeled. Autologous vessels are currently the most used material for
      small-diameter arterial replacement. Immune acceptance is a major advantage
      offered by this technique, but the time required is a limitation in emergency
      surgery. The need for a prosthetic graft that would have the same properties as a
      small-diameter conduit has led investigators to pursue many avenues in vascular
      biology. This article details the development of microvascular synthetic
      prostheses, clarifying the current status and the future aims. 

PMID- 23965593
TI  - An engineering analysis of the aortic valve dynamics in patients with rotary Left
      Ventricular Assist Devices.
AB  - The use of a rotary Left Ventricular Assist Device (LVAD) as a bridge-to-recovery
      treatment is gaining considerable attention in the LVAD research community. Using
      a mathematical model of the cardiovascular-LVAD system, this paper intends to
      define the critical control parameters in terms of power and rotational speed of
      the LVAD to ensure normal dynamics of the aortic valve for different levels of
      patient's activity and severity of heart failure. The effects of permanent
      closure of the aortic valve on the hemodynamics of the patient and the pump flow
      characteristics, if the critical control values are exceeded, are also examined.
      Additionally, LVAD power and speed control parameters that yield a given
      percentage of the cardiac cycle during which the aortic valve remains open are
      examined indicating that the severity of the heart failure is a very important
      factor in deciding the appropriateness of the LVAD as a bridge-to recovery
      treatment. 

PMID- 23965594
TI  - Bioreactors as engineering support to treat cardiac muscle and vascular disease.
AB  - Cardiovascular disease is the leading cause of morbidity and mortality in the
      Western World. The inability of fully differentiated, load-bearing cardiovascular
      tissues to in vivo regenerate and the limitations of the current treatment
      therapies greatly motivate the efforts of cardiovascular tissue engineering to
      become an effective clinical strategy for injured heart and vessels. For the
      effective production of organized and functional cardiovascular engineered
      constructs in vitro, a suitable dynamic environment is essential, and can be
      achieved and maintained within bioreactors. Bioreactors are technological devices
      that, while monitoring and controlling the culture environment and stimulating
      the construct, attempt to mimic the physiological milieu. In this study, a review
      of the current state of the art of bioreactor solutions for cardiovascular tissue
      engineering is presented, with emphasis on bioreactors and biophysical stimuli
      adopted for investigating the mechanisms influencing cardiovascular tissue
      development, and for eventually generating suitable cardiovascular tissue
      replacements. 

PMID- 23965595
TI  - Challenges and methodologies of fully automatic whole heart segmentation: a
      review.
AB  - Whole heart segmentation from magnetic resonance imaging or computed tomography
      is a prerequisite for many clinical applications. Since manual delineation can be
      tedious and subject to bias, automating such segmentation becomes increasingly
      popular in the image computing field. However, fully automatic whole heart
      segmentation is challenging and only limited studies were reported in the
      literature. This article reviews the existing techniques and analyzes the
      challenges and methodologies. The techniques are classified in terms of the types
      of the prior models and the algorithms used to fit the model to unseen images.
      The prior models include the atlases and the deformable models, and the fitting
      algorithms are further decomposed into four key techniques including localization
      of the whole heart, initialization of substructures, refinement of boundary
      delineation, and regularization of shapes. Finally, the validation issues,
      challenges, and future directions are discussed. 

PMID- 23965596
TI  - Chemothermal therapy for localized heating and ablation of tumor.
AB  - Chemothermal therapy is a new hyperthermia treatment on tumor using heat released
      from exothermic chemical reaction between the injected reactants and the diseased
      tissues. With the highly minimally invasive feature and localized heating
      performance, this method is expected to overcome the ubiquitous shortcomings
      encountered by many existing hyperthermia approaches in ablating irregular tumor.
      This review provides a relatively comprehensive review on the latest advancements
      and state of the art in chemothermal therapy. The basic principles and features
      of two typical chemothermal ablation strategies (acid-base neutralization
      reaction-enabled thermal ablation and alkali-metal-enabled thermal/chemical
      ablation) are illustrated. The prospects and possible challenges facing
      chemothermal ablation are analyzed. The chemothermal therapy is expected to open
      many clinical possibilities for precise tumor treatment in a minimally invasive
      way. 

PMID- 23965597
TI  - Design of electronic medical record user interfaces: a matrix-based method for
      improving usability.
AB  - This study examines a new approach of using the Design Structure Matrix (DSM)
      modeling technique to improve the design of Electronic Medical Record (EMR) user
      interfaces. The usability of an EMR medication dosage calculator used for placing
      orders in an academic hospital setting was investigated. The proposed method
      captures and analyzes the interactions between user interface elements of the EMR
      system and groups elements based on information exchange, spatial adjacency, and
      similarity to improve screen density and time-on-task. Medication dose adjustment
      task time was recorded for the existing and new designs using a cognitive
      simulation model that predicts user performance. We estimate that the design
      improvement could reduce time-on-task by saving an average of 21 hours of
      hospital physicians' time over the course of a month. The study suggests that the
      application of DSM can improve the usability of an EMR user interface. 

PMID- 23965598
TI  - Effectiveness of health sector reforms in reducing disparities in utilization of
      skilled birth attendants in Tanzania.
AB  - Improving maternal health is a Millennium Development Goal adopted at the 2000
      Millennium Summit of the United Nations. As part of the improving maternal health
      in Tanzania, it has been recommended that skilled birth attendants be present at
      all births to help reduce the high maternal mortality ratio. However, utilization
      of these attendants varies across socio-economic groups. The government of
      Tanzania has repeatedly attempted to carry out health sector reforms (HSRs) to
      alleviate disparities in health service utilization. In particular, around 1999,
      HSRs were incorporated into two approaches, including Decentralization by
      Devolution and Sector Wide Approach. This study aims to clarify the unresolved
      questions with little published evidence on the effect of HSRs on reducing
      disparities in utilization of skilled birth attendants across socio-economic
      groups over time. We used four cross-sectional datasets from the Tanzania
      Demographic and Health Survey: 1992, 1996, 1999, and 2004/05. Subjects included
      14,752 women of reproductive age (15-49 years) and data on the most recent birth
      in the 5 years before each survey. Logistic regression analysis was performed
      with the dependent variable of whether respondents utilized skilled birth
      attendants or not, and with the main independent variables of time and socio
      economic group. Results showed that the disparity in utilization of skilled birth
      attendants was significantly decreased from 1999 to 2004/05. These findings
      suggest that the two strategies, Decentralization by Devolution and Sector Wide
      Approach, in the process of HSRs are effective in reducing the disparities in
      utilization of skilled birth attendants among socio-economic groups. 

PMID- 23965599
TI  - Embryo sexing and sex chromosomal chimerism analysis by loop-mediated isothermal
      amplification in cattle and water buffaloes.
AB  - In domestic animals of the family Bovidae, sex preselection of offspring has been
      demanded for convenience of milk/beef production and animal breeding. Development
      of the nonsurgical embryo transfer technique and sexing methods of
      preimplantation embryos made it possible. Sexing based on detection of Y
      chromosome-specific DNA sequences is considered the most reliable method to date.
      PCR enables amplification of a target sequence from a small number of
      blastomeres. However, it requires technical skill and is time consuming.
      Furthermore, PCR has the risk of false positives because of DNA contamination
      during handling of the PCR products in duplicate PCR procedures and/or
      electrophoresis. Therefore, for embryo sexing to become widely used in the cattle
      embryo transfer industry, a simple, rapid and precise sexing method needs to be
      developed. Loop-mediated isothermal amplification (LAMP) is a novel DNA
      amplification method, and the reaction is carried out under isothermal conditions
      (range, 60 to 65 C) using DNA polymerase with strand displacement activity. When
      the target DNA is amplified by LAMP, a white precipitate derived from magnesium
      pyrophosphate (a by-product of the LAMP reaction) is observed. It is noteworthy
      that LAMP does not need special reagents or electrophoresis to detect the
      amplified DNA. This review describes the development and application of an embryo
      sexing method using LAMP in cattle and water buffaloes. 

PMID- 23965600
TI  - Seasonal time measurement during reproduction.
AB  - Most species living outside the tropical zone undergo physiological adaptations
      to seasonal environmental changes and changing day length (photoperiod); this
      phenomenon is called photoperiodism. It is well known that the circadian clock is
      involved in the regulation of photoperiodism such as seasonal reproduction, but
      the mechanism underlying circadian clock regulation of photoperiodism remains
      unclear. Recent molecular analysis have revealed that, in mammals and birds, the
      pars tuberalis (PT) of the pituitary gland acts as the relay point from light
      receptors, which receive information about the photoperiod, to the endocrine
      responses. Long-day (LD)-induced thyroid-stimulating hormone (TSH) in the PT acts
      as a master regulator of seasonal reproduction in the ependymal cells (ECs)
      within the mediobasal hypothalamus (MBH) and activates thyroid hormone (TH) by
      inducing the expression of type 2 deiodinase in both LD and short-day (SD)
      breeding animals. Furthermore, the circadian clock has been found to be localized
      in the PT and ECs as well as in the circadian pacemaker(s). This review purposes
      to summarize the current knowledge concerning the involvement of the
      neuroendocrine system and circadian clock in seasonal reproduction. 

PMID- 23965601
TI  - Sperm storage in the female reproductive tract in birds.
AB  - The ability to store sperm in the female genital tract is frequently observed in
      vertebrates as well as in invertebrates. Because of the presence of a system that
      maintains the ejaculated sperm alive in the female reproductive tract in a
      variety of animals, this strategy appears to be advantageous for animal
      reproduction. Although the occurrence and physiological reasons for sperm storage
      have been reported extensively in many species, the mechanism of sperm storage in
      the female reproductive tract has been poorly understood until recently. In avian
      species, the specialized simple tubular invaginations referred to as sperm
      storage tubules (SSTs) are found in the oviduct as a sperm storage organ. In this
      review, we summarize the current understanding of the mechanism of sperm uptake
      into the SSTs, maintenance within it, and controlled release of the sperm from
      the SSTs. Since sperm storage in avian species occurs at high body temperatures
      (i.e., 41 C), elucidation of the mechanism for sperm storage may lead to the
      development of new strategies for sperm preservation at ambient temperatures, and
      these could be used in a myriad of applications in the field of reproduction. 

PMID- 23965602
TI  - Excessively long hospital stays after trauma are not related to the severity of
      illness: let's aim to the right target!
AB  - IMPORTANCE: Reduction in length of hospital stay is a veritable target in
      reducing the overall costs of health care. However, many existing approaches are
      flawed because the assumptions of what cause excessive length of stay are
      incorrect; we methodically identified the right targets in this study. OBJECTIVE:
      To identify the causes of excessively prolonged hospitalization (ExProH) in
      trauma patients. DESIGN: The trauma registry, billing databases, and medical
      records of trauma admissions were reviewed. Excessively prolonged hospitalization
      was defined by the standard method used by insurers, which is a hospital stay
      that exceeds the Diagnosis Related Group-based trim point. The causes of ExProH
      were explored in a unique potentially avoidable days database, used by our
      hospital's case managers to track discharge delays. SETTING: Level I academic
      trauma center. PARTICIPANTS: Adult trauma patients admitted between January 1,
      2006, and December 31, 2010. MAIN OUTCOMES AND MEASURES: Excessively prolonged
      hospitalization and hospital cost. RESULTS: Of 3237 patients, 155 (5%) had
      ExProH. The patients with ExProH compared with non-ExProH patients were older
      (mean [SD] age, 53 [21] vs 47 [22] years, respectively; P = .001), were more
      likely to have blunt trauma (92% vs 84%, respectively; P = .03), were more likely
      to be self-payers (16% vs 11%, respectively; P = .02) or covered by
      Medicare/Medicaid (41% vs 30%, respectively; P = .002), were more likely to be
      discharged to post-acute care facilities than home (65% vs 35%, respectively; P <
      .001), and had higher hospitalization cost (mean, $54 646 vs $18 444,
      respectively; P < .001). Both groups had similar Injury Severity Scores, Revised
      Trauma Scores, baseline comorbidities, and in-hospital complication rates.
      Independent predictors of mortality were discharge to a rehabilitation facility
      (odds ratio = 4.66; 95% CI, 2.71-8.00; P < .001) or other post-acute care
      facility (odds ratio = 5.04; 95% CI, 2.52-10.05; P < .001) as well as insurance
      type that was Medicare/Medicaid (odds ratio = 1.70; 95% CI, 1.06-2.72; P = .03)
      or self-pay (odds ratio = 2.43; 95% CI, 1.35-4.37; P = .003). The reasons for
      discharge delays were clinical in only 20% of the cases. The remaining discharges
      were excessively delayed because of difficulties in rehabilitation facility
      placement (47%), in-hospital operational delays (26%), or payer-related issues
      (7%). CONCLUSIONS AND RELEVANCE: System-related issues, not severity of illness,
      prolong hospital stay excessively. Cost-reduction efforts should target
      operational bottlenecks between acute and postacute care.

PMID- 23965603
TI  - Absence of beneficial effects on rabbit sperm cell cryopreservation by several
      antioxidant agents.
AB  - The generation of reactive oxygen species associated with cryopreservation could
      be responsible for mammalian sperm damage and the limitable value of stored semen
      in artificial insemination. The aim of this study was to assess several
      antioxidant agents supplemented in a commercial freezing extender (Gent B(r)) in
      order to improve post-thaw rabbit sperm quality. Ejaculates of 26 New Zealand
      White rabbit bucks were collected, evaluated and frozen using a conventional
      protocol. Antioxidant agents were tested at different concentrations: bovine
      serum albumin (BSA; 5, 30 or 60 mg/ml), retinol (RO; 50, 100 or 200 MUM) and
      retinyl (RI; 0.282 or 2.82 MUg/ml). Per cent viability, morphological
      abnormalities and intact acrosomes were determined using eosin-nigrosin staining.
      Motility and progressivity were analyzed by computer-assisted sperm analysis
      (CASA). In general, all sperm quality parameters were negatively affected by the
      cryopreservation process, the largest effect seen was for total motility. The
      addition of antioxidant agents did not improve thaw sperm quality. Furthermore,
      for RI groups a significant decrease in sperm quality parameters was recorded. In
      conclusion, rabbit sperm quality is negatively affected by the cryopreservation
      process. To our knowledge this report is the first using these antioxidants to
      supplement rabbit freezing extender. BSA and RO at concentrations used in the
      study did not improve sperm quality parameters after thawing, whereas RI
      supplementation appeared to be toxic. More studies are required to find the
      appropriate antioxidants necessary and their most effective concentrations to
      improve rabbit post-thaw sperm quality.

PMID- 23965605
TI  - Electroconvulsive therapy attenuates dendritic arborization in the basolateral
      amygdala.
AB  - Stress and depression are associated with aberrant neuroplasticity in the
      amygdala: there is increased dendritic arborization and synaptogenesis, perhaps
      explaining the increased anxiety and fear that are often apparent in depressed
      patients. Light microscopy images are presented, which show that 6 once-daily
      high (but not low)-dose electroconvulsive shocks attenuated dendritic
      arborization in the basolateral amygdala of Wistar rats, which changes were
      apparent even 1 month after the last electroconvulsive shock. These changes may
      explain a part of the mechanism of action of electroconvulsive therapy in
      conditions such as depression and posttraumatic stress disorder. 

PMID- 23965604
TI  - Electroconvulsive therapy anesthesia technique: minimalist versus maximally
      managed.

PMID- 23965606
TI  - Effective treatment of catatonia by combination of benzodiazepine and
      electroconvulsive therapy.
AB  - OBJECTIVE: Catatonia, a motor dysregulation syndrome, can emerge in numerous
      psychiatric disorders, mainly in schizophrenia and mood disorders, and metabolic
      and endocrine disorders such as infections, toxic states, epilepsy, and traumatic
      brain injury. In our study, we aimed to investigate demographic, clinical, and
      treatment-related characteristics of catatonic patients managed in our inpatient
      clinic. METHODS: The medical records of 57 patients diagnosed to have catatonia
      according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, Text Revision, criteria who were admitted to the inpatient psychiatry
      clinic of the Gaziantep University School of Medicine between 1 January, 2003,
      and 31 December, 2011, were retrospectively reviewed. RESULTS: In patients with
      catatonia, mood disorders (63.2%) were found to be the most common underlying or
      primary disease, whereas mutism (47.4%) was found to be the most common catatonic
      symptom. There was a comorbid medical condition in 9 patients (15.8%). Patients
      underwent an average of 9.00 electroconvulsive therapy (ECT) sessions. Among 57
      patients with catatonia, catatonic symptoms were resolved in 57 patients (100%)
      by benzodiazepine and ECT. CONCLUSIONS: In our study, full recovery was achieved
      in catatonia by benzodiazepine plus ECT combination. As a result, we recommend
      combined ECT and benzodiazepine for catatonia.

PMID- 23965607
TI  - Effects of propofol and ketamine as combined anesthesia for electroconvulsive
      therapy in patients with depressive disorder: a perspective from
      anesthesiologists.

PMID- 23965608
TI  - Electroconvulsive therapy and Klinefelter syndrome.
AB  - Klinefelter syndrome is a common sex chromosome disorder characterized by the
      presence of 1 or more extra X chromosomes, and the most prevalent karyotype is
      47,XXY. Epidemiological studies have showed that patients with Klinefelter
      syndrome had a significantly increased risk of psychosis. We presented a case of
      a patient with Klinefelter syndrome who was characterized by psychiatric
      symptoms. The patients had been refractory to clozapine and sodium valproate, but
      a remarkable improvement occurred after a cycle of 11 sessions of modified
      electroconvulsive therapy. 

PMID- 23965609
TI  - Rapid improvement of auditory verbal hallucinations in schizophrenia after add-on
      treatment with transcranial direct-current stimulation.
AB  - Treatment of nonresponsive auditory hallucinations in schizophrenia have been
      reported to improve with transcranial direct-current stimulation. This case
      description illustrates the use of add-on transcranial direct-current stimulation
      for rapid amelioration of auditory hallucinations in schizophrenia during the
      acute phase. Because transcranial direct-current stimulation is safe, largely
      well tolerated, and relatively inexpensive, this add-on treatment option is worth
      exploring through further rigorous studies. 

PMID- 23965610
TI  - Topiramate for post-electroconvulsive therapy headaches.
AB  - Headache is a common adverse effect of electroconvulsive therapy. The analgesic
      medications acetaminophen, nonsteroidal anti-inflammatory agents, muscle
      relaxants, or narcotics usually produce only short-term benefit. Topiramate was
      an effective therapy for a post-electroconvulsive therapy headache that did not
      respond to typical pain medicines. 

PMID- 23965611
TI  - Use of electroconvulsive therapy in an adolescent with systemic lupus
      erythematosus for management of depression.
AB  - Use of electroconvulsive therapy (ECT) has been infrequently described in
      patients with systemic lupus erythematosus and is most commonly used in patients
      with catatonia. In this report, we describe the use of ECT in a young adolescent
      girl who had bipolar affective disorder associated with systemic lupus
      erythematosus and was treated with ECT for the depressive episode. The patient
      achieved remission with a course of 6 ECT treatments. 

PMID- 23965612
TI  - Electroconvulsive therapy for a patient with persistent tardive dyskinesia: a
      case report and literature review.
AB  - Tardive dyskinesia (TD) is a movement disorder that presents with abnormal,
      involuntary, and irregular choreoathetoid movements involving mouth, tongue,
      face, trunk, or extremities after prolonged use of dopamine receptor-blocking
      agents. Currently, there is still a lack of effective treatment for it. Here, we
      report a female patient with paranoid schizophrenia, who has had persistent TD
      for 8 years. After electroconvulsive therapy (ECT) was performed, both of her
      psychotic symptoms and dyskinetic movements were improved. The efficacy and
      potential clinical variables of ECT in the treatment of TD were reviewed. 

PMID- 23965613
TI  - Divergent astrovirus associated with neurologic disease in cattle.
AB  - Using viral metagenomics of brain tissue from a young adult crossbreed steer with
      acute onset of neurologic disease, we sequenced the complete genome of a novel
      astrovirus (BoAstV-NeuroS1) that was phylogenetically related to an ovine
      astrovirus. In a retrospective analysis of 32 cases of bovine encephalitides of
      unknown etiology, 3 other infected animals were detected by using PCR and in situ
      hybridization for viral RNA. Viral RNA was restricted to the nervous system and
      detected in the cytoplasm of affected neurons within the spinal cord, brainstem,
      and cerebellum. Microscopically, the lesions were of widespread neuronal
      necrosis, microgliosis, and perivascular cuffing preferentially distributed in
      gray matter and most severe in the cerebellum and brainstem, with increasing
      intensity caudally down the spinal cord. These results suggest that infection
      with BoAstV-NeuroS1 is a potential cause of neurologic disease in cattle. 

PMID- 23965614
TI  - Evolution of pollination niches and floral divergence in the generalist plant
      Erysimum mediohispanicum.
AB  - BACKGROUND AND AIMS: How generalist plants diverge in response to pollinator
      selection without becoming specialized is still unknown. This study explores this
      question, focusing on the evolution of the pollination system in the pollination
      generalist Erysimum mediohispanicum (Brassicaceae). METHODS: Pollinator
      assemblages were surveyed from 2001 to 2010 in 48 geo-referenced populations
      covering the entire geographic distribution of E. mediohispanicum. Bipartite
      modularity, a complex network tool, was used to find the pollination niche of
      each population. Evolution of the pollination niches and the correlated evolution
      of floral traits and pollination niches were explored using within-species
      comparative analyses. KEY RESULTS: Despite being generalists, the E.
      mediohispanicum populations studied can be classified into five pollination
      niches. The boundaries between niches were not sharp, the niches differing among
      them in the relative frequencies of the floral visitor functional groups. The
      absence of spatial autocorrelation and phylogenetic signal indicates that the
      niches were distributed in a phylogeographic mosaic. The ancestral E.
      mediohispanicum populations presumably belonged to the niche defined by a high
      number of beetle and ant visits. A correlated evolution was found between
      pollination niches and some floral traits, suggesting the existence of generalist
      pollination ecotypes. CONCLUSIONS: It is conjectured that the geographic
      variation in pollination niches has contributed to the observed floral divergence
      in E. mediohispanicum. The process mediating this floral divergence presumably
      has been adaptive wandering, but the adaptation to the local pollinator faunas
      has been not universal. The outcome is a landscape where a few populations
      locally adapted to their pollination environment (generalist pollination
      ecotypes) coexist with many populations where this local adaptation has failed
      and where the plant phenotype is not primarily shaped by pollinators.

PMID- 23965615
TI  - Auxin increases the hydrogen peroxide (H2O2) concentration in tomato (Solanum
      lycopersicum) root tips while inhibiting root growth.
AB  - BACKGROUND AND AIMS: The hormone auxin and reactive oxygen species (ROS) regulate
      root elongation, but the interactions between the two pathways are not well
      understood. The aim of this study was to investigate how auxin interacts with ROS
      in regulating root elongation in tomato, Solanum lycopersicum. METHODS: Wild-type
      and auxin-resistant mutant, diageotropica (dgt), of tomato (S. lycopersicum
      'Ailsa Craig') were characterized in terms of root apical meristem and elongation
      zone histology, expression of the cell-cycle marker gene Sl-CycB1;1, accumulation
      of ROS, response to auxin and hydrogen peroxide (H2O2), and expression of ROS
      related mRNAs. KEY RESULTS: The dgt mutant exhibited histological defects in the
      root apical meristem and elongation zone and displayed a constitutively increased
      level of hydrogen peroxide (H2O2) in the root tip, part of which was detected in
      the apoplast. Treatments of wild-type with auxin increased the H2O2 concentration
      in the root tip in a dose-dependent manner. Auxin and H2O2 elicited similar
      inhibition of cell elongation while bringing forth differential responses in
      terms of meristem length and number of cells in the elongation zone. Auxin
      treatments affected the expression of mRNAs of ROS-scavenging enzymes and less
      significantly mRNAs related to antioxidant level. The dgt mutation resulted in
      resistance to both auxin and H2O2 and affected profoundly the expression of mRNAs
      related to antioxidant level. CONCLUSIONS: The results indicate that auxin
      regulates the level of H2O2 in the root tip, so increasing the auxin level
      triggers accumulation of H2O2 leading to inhibition of root cell elongation and
      root growth. The dgt mutation affects this pathway by reducing the auxin
      responsiveness of tissues and by disrupting the H2O2 homeostasis in the root tip.

PMID- 23965616
TI  - The timetable for allopolyploidy in flowering plants.
AB  - BACKGROUND: Our understanding of the processes and dynamics of allopolyploid
      speciation, the long-term consequences of ploidal change, and the genetic and
      chromosomal changes in new emerged allopolyploids has substantially increased
      during the past few decades. Yet we remain uncertain about the time since lineage
      divergence when two taxa are capable of spawning such entities. Indeed, the
      matter has seemed intractable. Knowledge of the window of opportunity for
      allopolyploid production is very important because it provides temporal insight
      into a key evolutionary process, and a temporal reference against which other
      modes of speciation may be measured. SCOPE: This Viewpoint paper reviews and
      integrates published information on the crossability of herbaceous species and
      the fertility of their hybrids in relation to species' divergence times. Despite
      limitations in methodology and sampling, the estimated times to hybrid sterility
      are somewhat congruent across disparate lineages. Whereas the waiting time for
      hybrid sterility is roughly 4-5 million years, the waiting time for cross
      incompatibility is roughly 8-10 million years, sometimes considerably more.
      Strict allopolyploids may be formed in the intervening time window. The
      progenitors of several allopolyploids diverged between 4 and 6 million years
      before allopolyploid synthesis, as expected. This is the first study to propose a
      general temporal framework for strict allopolyploidy. This Viewpoint paper
      hopefully will stimulate interest in studying the tempo of speciation and the
      tempo of reproductive isolation in general.

PMID- 23965617
TI  - Tapetum and middle layer control male fertility in Actinidia deliciosa.
AB  - BACKGROUND AND AIMS: Dioecism characterizes many crop species of economic value,
      including kiwifruit (Actinidia deliciosa). Kiwifruit male sterility occurs at the
      microspore stage. The cell walls of the microspores and the pollen of the male
      sterile and male-fertile flowers, respectively, differ in glucose and galactose
      levels. In numerous plants, pollen formation involves normal functioning and
      degeneration timing of the tapetum, with calcium and carbohydrates provided by
      the tapetum essential for male fertility. The aim of this study was to determine
      whether the anther wall controls male fertility in kiwifruit, providing calcium
      and carbohydrates to the microspores. METHODS: The events occurring in the anther
      wall and microspores of male-fertile and male-sterile anthers were investigated
      by analyses of light microscopy, epifluorescence, terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labelling (TUNEL assay) and transmission
      electron microscopy coupled with electron spectroscopy. The possibility that male
      sterility was related to anther tissue malfunctioning with regard to
      calcium/glucose/galactose provision to the microspores was also investigated by
      in vitro anther culture. KEY RESULTS: Both tapetum and the middle layer showed
      secretory activity and both degenerated by programmed cell death (PCD), but PCD
      was later in male-sterile than in male-fertile anthers. Calcium accumulated in
      cell walls of the middle layer and tapetum and in the exine of microspores and
      pollen, reaching higher levels in anther wall tissues and dead microspores of
      male-sterile anthers. A specific supply of glucose and calcium induced normal
      pollen formation in in vitro-cultured anthers of the male-sterile genotype.
      CONCLUSIONS: The results show that male sterility in kiwifruit is induced by
      anther wall tissues through prolonged secretory activity caused by a delay in
      PCD, in the middle layer in particular. In vitro culture results support the
      sporophytic control of male fertility in kiwifruit and open the way to
      applications to overcome dioecism and optimize kiwifruit production.

PMID- 23965618
TI  - R292K substitution and drug susceptibility of influenza A(H7N9) viruses.
AB  - Neuraminidase inhibitors are the only licensed antiviral medications available to
      treat avian influenza A(H7N9) virus infections in humans. According to a
      neuraminidase inhibition assay, an R292K substitution reduced antiviral efficacy
      of inhibitors, especially oseltamivir, and decreased viral fitness in cell
      culture. Monitoring emergence of R292K-carrying viruses using a pH-modified
      neuraminidase inhibition assay should be considered. 

PMID- 23965619
TI  - Microbial colonization influences early B-lineage development in the gut lamina
      propria.
AB  - The RAG1/RAG2 endonuclease (RAG) initiates the V(D)J recombination reaction that
      assembles immunoglobulin heavy (IgH) and light (IgL) chain variable region exons
      from germline gene segments to generate primary antibody repertoires. IgH V(D)J
      assembly occurs in progenitor (pro-) B cells followed by that of IgL in precursor
      (pre-) B cells. Expression of IgH MU and IgL (Igkappa or Iglambda) chains
      generates IgM, which is expressed on immature B cells as the B-cell antigen
      binding receptor (BCR). Rag expression can continue in immature B cells, allowing
      continued Igkappa V(D)J recombination that replaces the initial VkappaJkappa exon
      with one that generates a new specificity. This 'receptor editing' process, which
      can also lead to Iglambda V(D)J recombination and expression, provides a
      mechanism whereby antigen encounter at the Rag-expressing immature B-cell stage
      helps shape pre-immune BCR repertoires. As the major site of postnatal B-cell
      development, the bone marrow is the principal location of primary immunoglobulin
      repertoire diversification in mice. Here we report that early B-cell development
      also occurs within the mouse intestinal lamina propria (LP), where the associated
      V(D)J recombination/receptor editing processes modulate primary LP immunoglobulin
      repertoires. At weanling age in normally housed mice, the LP contains a
      population of Rag-expressing B-lineage cells that harbour intermediates
      indicative of ongoing V(D)J recombination and which contain cells with pro-B, pre
      B and editing phenotypes. Consistent with LP-specific receptor editing, Rag
      expressing LP B-lineage cells have similar VH repertoires, but significantly
      different Vkappa repertoires, compared to those of Rag2-expressing bone marrow
      counterparts. Moreover, colonization of germ-free mice leads to an increased
      ratio of Iglambda-expressing versus Igkappa-expressing B cells specifically in
      the LP. We conclude that B-cell development occurs in the intestinal mucosa,
      where it is regulated by extracellular signals from commensal microbes that
      influence gut immunoglobulin repertoires. 

PMID- 23965620
TI  - Changes in North Atlantic nitrogen fixation controlled by ocean circulation.
AB  - In the ocean, the chemical forms of nitrogen that are readily available for
      biological use (known collectively as 'fixed' nitrogen) fuel the global
      phytoplankton productivity that exports carbon to the deep ocean. Accordingly,
      variation in the oceanic fixed nitrogen reservoir has been proposed as a cause of
      glacial-interglacial changes in atmospheric carbon dioxide concentration. Marine
      nitrogen fixation, which produces most of the ocean's fixed nitrogen, is thought
      to be affected by multiple factors, including ocean temperature and the
      availability of iron and phosphorus. Here we reconstruct changes in North
      Atlantic nitrogen fixation over the past 160,000 years from the shell-bound
      nitrogen isotope ratio ((15)N/(14)N) of planktonic foraminifera in Caribbean Sea
      sediments. The observed changes cannot be explained by reconstructed changes in
      temperature, the supply of (iron-bearing) dust or water column denitrification.
      We identify a strong, roughly 23,000-year cycle in nitrogen fixation and suggest
      that it is a response to orbitally driven changes in equatorial Atlantic
      upwelling, which imports 'excess' phosphorus (phosphorus in stoichiometric excess
      of fixed nitrogen) into the tropical North Atlantic surface. In addition, we find
      that nitrogen fixation was reduced during glacial stages 6 and 4, when North
      Atlantic Deep Water had shoaled to become glacial North Atlantic intermediate
      water, which isolated the Atlantic thermocline from excess phosphorus-rich mid
      depth waters that today enter from the Southern Ocean. Although modern studies
      have yielded diverse views of the controls on nitrogen fixation, our
      palaeobiogeochemical data suggest that excess phosphorus is the master variable
      in the North Atlantic Ocean and indicate that the variations in its supply over
      the most recent glacial cycle were dominated by the response of regional ocean
      circulation to the orbital cycles. 

PMID- 23965621
TI  - Immunology: B-cell development in the gut.

PMID- 23965622
TI  - Stimulated X-ray emission for materials science.
AB  - Resonant inelastic X-ray scattering and X-ray emission spectroscopy can be used
      to probe the energy and dispersion of the elementary low-energy excitations that
      govern functionality in matter: vibronic, charge, spin and orbital excitations. A
      key drawback of resonant inelastic X-ray scattering has been the need for high
      photon densities to compensate for fluorescence yields of less than a per cent
      for soft X-rays. Sample damage from the dominant non-radiative decays thus limits
      the materials to which such techniques can be applied and the spectral resolution
      that can be obtained. A means of improving the yield is therefore highly
      desirable. Here we demonstrate stimulated X-ray emission for crystalline silicon
      at photon densities that are easily achievable with free-electron lasers. The
      stimulated radiative decay of core excited species at the expense of non
      radiative processes reduces sample damage and permits narrow-bandwidth detection
      in the directed beam of stimulated radiation. We deduce how stimulated X-ray
      emission can be enhanced by several orders of magnitude to provide, with high
      yield and reduced sample damage, a superior probe for low-energy excitations and
      their dispersion in matter. This is the first step to bringing nonlinear X-ray
      physics in the condensed phase from theory to application. 

PMID- 23965625
TI  - Life history trade-offs at a single locus maintain sexually selected genetic
      variation.
AB  - Sexual selection, through intra-male competition or female choice, is assumed to
      be a source of strong and sustained directional selection in the wild. In the
      presence of such strong directional selection, alleles enhancing a particular
      trait are predicted to become fixed within a population, leading to a decrease in
      the underlying genetic variation. However, there is often considerable genetic
      variation underlying sexually selected traits in wild populations, and
      consequently, this phenomenon has become a long-discussed issue in the field of
      evolutionary biology. In wild Soay sheep, large horns confer an advantage in
      strong intra-sexual competition, yet males show an inherited polymorphism for
      horn type and have substantial genetic variation in their horn size. Here we show
      that most genetic variation in this trait is maintained by a trade-off between
      natural and sexual selection at a single gene, relaxin-like receptor 2 (RXFP2).
      We found that an allele conferring larger horns, Ho(+), is associated with higher
      reproductive success, whereas a smaller horn allele, Ho(P), confers increased
      survival, resulting in a net effect of overdominance (that is, heterozygote
      advantage) for fitness at RXFP2. The nature of this trade-off is simple relative
      to commonly proposed explanations for the maintenance of sexually selected
      traits, such as genic capture ('good genes') and sexually antagonistic selection.
      Our results demonstrate that by identifying the genetic architecture of trait
      variation, we can determine the principal mechanisms maintaining genetic
      variation in traits under strong selection and explain apparently counter
      evolutionary observations. 

PMID- 23965626
TI  - Mechanism of Trypanosoma brucei gambiense resistance to human serum.
AB  - The African parasite Trypanosoma brucei gambiense accounts for 97% of human
      sleeping sickness cases. T. b. gambiense resists the specific human innate
      immunity acting against several other tsetse-fly-transmitted trypanosome species
      such as T. b. brucei, the causative agent of nagana disease in cattle. Human
      immunity to some African trypanosomes is due to two serum complexes designated
      trypanolytic factors (TLF-1 and -2), which both contain haptoglobin-related
      protein (HPR) and apolipoprotein LI (APOL1). Whereas HPR association with
      haemoglobin (Hb) allows TLF-1 binding and uptake via the trypanosome receptor
      TbHpHbR (ref. 5), TLF-2 enters trypanosomes independently of TbHpHbR (refs 4, 5).
      APOL1 kills trypanosomes after insertion into endosomal/lysosomal membranes. Here
      we report that T. b. gambiense resists TLFs via a hydrophobic beta-sheet of the
      T. b. gambiense-specific glycoprotein (TgsGP), which prevents APOL1 toxicity and
      induces stiffening of membranes upon interaction with lipids. Two additional
      features contribute to resistance to TLFs: reduction of sensitivity to APOL1
      requiring cysteine protease activity, and TbHpHbR inactivation due to a L210S
      substitution. According to such a multifactorial defence mechanism, transgenic
      expression of T. b. brucei TbHpHbR in T. b. gambiense did not cause parasite
      lysis in normal human serum. However, these transgenic parasites were killed in
      hypohaptoglobinaemic serum, after high TLF-1 uptake in the absence of haptoglobin
      (Hp) that competes for Hb and receptor binding. TbHpHbR inactivation preventing
      high APOL1 loading in hypohaptoglobinaemic serum may have evolved because of the
      overlapping endemic area of T. b. gambiense infection and malaria, the main cause
      of haemolysis-induced hypohaptoglobinaemia in western and central Africa. 

PMID- 23965630
TI  - Neuroscience: Bacteria get on your nerves.

PMID- 23965627
TI  - Bacteria activate sensory neurons that modulate pain and inflammation.
AB  - Nociceptor sensory neurons are specialized to detect potentially damaging
      stimuli, protecting the organism by initiating the sensation of pain and
      eliciting defensive behaviours. Bacterial infections produce pain by unknown
      molecular mechanisms, although they are presumed to be secondary to immune
      activation. Here we demonstrate that bacteria directly activate nociceptors, and
      that the immune response mediated through TLR2, MyD88, T cells, B cells, and
      neutrophils and monocytes is not necessary for Staphylococcus aureus-induced pain
      in mice. Mechanical and thermal hyperalgesia in mice is correlated with live
      bacterial load rather than tissue swelling or immune activation. Bacteria induce
      calcium flux and action potentials in nociceptor neurons, in part via bacterial N
      formylated peptides and the pore-forming toxin alpha-haemolysin, through distinct
      mechanisms. Specific ablation of Nav1.8-lineage neurons, which include
      nociceptors, abrogated pain during bacterial infection, but concurrently
      increased local immune infiltration and lymphadenopathy of the draining lymph
      node. Thus, bacterial pathogens produce pain by directly activating sensory
      neurons that modulate inflammation, an unsuspected role for the nervous system in
      host-pathogen interactions. 

PMID- 23965631
TI  - Atomic roughness enhanced friction on hydrogenated graphene.
AB  - Atomic friction on hydrogenated graphene is investigated using molecular dynamics
      simulations. Hydrogenation is found to increase friction significantly, and the
      atomic-level information provided by the simulations reveals that atomic
      roughness induced by hydrogenation is the primary cause of the friction
      enhancement. Other proposed mechanisms, specifically adhesion and rigidity, are
      excluded based on the simulation results and analyses performed using the Prandtl
      Tomlinson model. In addition, it is found that friction does not monotonically
      increase with hydrogen coverage on the graphene surface; instead, a maximum
      friction is observed at a hydrogen coverage between 5 and 10%. 

PMID- 23965628
TI  - Germline mitochondrial DNA mutations aggravate ageing and can impair brain
      development.
AB  - Ageing is due to an accumulation of various types of damage, and mitochondrial
      dysfunction has long been considered to be important in this process. There is
      substantial sequence variation in mammalian mitochondrial DNA (mtDNA), and the
      high mutation rate is counteracted by different mechanisms that decrease maternal
      transmission of mutated mtDNA. Despite these protective mechanisms, it is
      becoming increasingly clear that low-level mtDNA heteroplasmy is quite common and
      often inherited in humans. We designed a series of mouse mutants to investigate
      the extent to which inherited mtDNA mutations can contribute to ageing. Here we
      report that maternally transmitted mtDNA mutations can induce mild ageing
      phenotypes in mice with a wild-type nuclear genome. Furthermore, maternally
      transmitted mtDNA mutations lead to anticipation of reduced fertility in mice
      that are heterozygous for the mtDNA mutator allele (PolgA(wt/mut)) and aggravate
      premature ageing phenotypes in mtDNA mutator mice (PolgA(mut/mut)). Unexpectedly,
      a combination of maternally transmitted and somatic mtDNA mutations also leads to
      stochastic brain malformations. Our findings show that a pre-existing mutation
      load will not only allow somatic mutagenesis to create a critically high total
      mtDNA mutation load sooner but will also increase clonal expansion of mtDNA
      mutations to enhance the normally occurring mosaic respiratory chain deficiency
      in ageing tissues. Our findings suggest that maternally transmitted mtDNA
      mutations may have a similar role in aggravating aspects of normal human ageing. 

PMID- 23965623
TI  - The genesis and source of the H7N9 influenza viruses causing human infections in
      China.
AB  - A novel H7N9 influenza A virus first detected in March 2013 has since caused more
      than 130 human infections in China, resulting in 40 deaths. Preliminary analyses
      suggest that the virus is a reassortant of H7, N9 and H9N2 avian influenza
      viruses, and carries some amino acids associated with mammalian receptor binding,
      raising concerns of a new pandemic. However, neither the source populations of
      the H7N9 outbreak lineage nor the conditions for its genesis are fully known.
      Using a combination of active surveillance, screening of virus archives, and
      evolutionary analyses, here we show that H7 viruses probably transferred from
      domestic duck to chicken populations in China on at least two independent
      occasions. We show that the H7 viruses subsequently reassorted with enzootic H9N2
      viruses to generate the H7N9 outbreak lineage, and a related previously
      unrecognized H7N7 lineage. The H7N9 outbreak lineage has spread over a large
      geographic region and is prevalent in chickens at live poultry markets, which are
      thought to be the immediate source of human infections. Whether the H7N9 outbreak
      lineage has, or will, become enzootic in China and neighbouring regions requires
      further investigation. The discovery here of a related H7N7 influenza virus in
      chickens that has the ability to infect mammals experimentally, suggests that H7
      viruses may pose threats beyond the current outbreak. The continuing prevalence
      of H7 viruses in poultry could lead to the generation of highly pathogenic
      variants and further sporadic human infections, with a continued risk of the
      virus acquiring human-to-human transmissibility. 

PMID- 23965632
TI  - Split cord malformation.

PMID- 23965633
TI  - Impact of diabetes mellitus on arterial stiffness in a representative sample of
      an urban Brazilian population.
AB  - BACKGROUND: Independent of other cardiovascular (CV) risk factors, increased
      arterial stiffness has been established as a predictor of morbidity and
      mortality. The main aim of this study was to investigate the impact of diabetes
      on arterial stiffness in a representative sample of an urban Brazilian population
      plus Amerindians. METHODS: A total of 1,415 individuals from the general
      population were randomly selected plus 588 Amerindians from a native community in
      Brazil. In addition, a sub-sample of 380 individuals from the general population
      had 5-year follow-up data. Pulse wave velocity (PWV) was measured with a non
      invasive automatic device (Complior, Colson; Garges les Gonesses, France) and
      increased arterial stiffness was defined as PWV >= 12 m/s. RESULTS: In the
      overall group, diabetic individuals had higher frequencies of increased arterial
      stiffness and hypertension. They also had higher values of PWV, body mass index,
      total cholesterol, triglycerides, systolic and diastolic blood pressures compared
      to non-diabetic individuals (p < 0.01). In an analysis stratified by
      hypertension, PWV values and increased arterial stiffness frequency were higher
      in diabetic individuals in both groups (hypertensive and non-hypertensive) (p <
      0.05). Furthermore, higher risk for increased arterial stiffness was observed in
      the diabetic individuals from the overall group (OR = 2.27; CI = 1.47-3.52, p <
      0.001) and from the hypertensive group (OR = 2.70; CI = 1.58-4.75, p < 0.001),
      adjusted for covariates. Regarding the ethnic stratification, diabetic
      individuals from Amerindian, White, and Mulatto (mixed-race) groups had higher
      PWV values and a greater frequency of increased arterial stiffness compared to
      non-diabetic individuals. Both diabetic and non-diabetic individuals had higher
      PWV values after 5 years. There was no significant difference in the 5-year PWV
      progression in diabetic compared to non-diabetic individuals. CONCLUSIONS: These
      results confirm, in a sample of Brazilian population, that the presence of
      diabetes is associated with increased arterial stiffness and it may contribute in
      part to increased cardiovascular risk in diabetic patients.

PMID- 23965635
TI  - Psychosocial experiences of parents of infants with hypoplastic left heart
      syndrome in the PICU.
AB  - OBJECTIVE: To evaluate the psychosocial status of mothers and fathers of infants
      with hypoplastic left heart syndrome while in the PICU. DESIGN: A retrospective
      study combining interviews and psychometric testing of parents. SETTING: Tertiary
      hospital PICU. SUBJECTS: Twenty-nine parents (16 mothers and 13 fathers) of
      surviving children. INTERVENTION: A semistructured face-to-face interview was
      conducted to explore parental experiences, and a Structured Clinical Interview
      for Diagnosis-Clinical Version (posttraumatic stress disorder module) was
      conducted to determine the possibility of an acute stress disorder or a
      posttraumatic stress disorder. MEASUREMENT AND MAIN RESULTS: All parents reported
      multiple stresses which commenced with their infant's diagnosis and endured
      throughout their infant's time in PICU. The Structured Clinical Interview for
      Diagnosis revealed that acute stress disorder or posttraumatic stress disorder
      developed in 24 parents (83%). Of 18 parents whose infants were diagnosed with
      hypoplastic left heart syndrome in utero, eight of nine mothers (88%) and six of
      nine fathers (66%) had posttraumatic stress disorder. Of 11 parents whose infants
      were diagnosed with hypoplastic left heart syndrome postbirth, six of seven
      mothers had acute stress disorder and one mother had posttraumatic stress
      disorder, and of four fathers, two fathers had acute stress disorder and one
      father had posttraumatic stress disorder. The prevalence of parental stress
      related disorder was not different between mothers and fathers (p = 0.85). Only
      five parents were free of traumatic stress-related illness. Parents also
      experienced losses. Many parents were marginalized from their infant's care by
      the environment of PICU. Fifty percent of mothers experienced difficulties with
      parental-infant bonding. Ten parents (34%) began the process of adaptation to
      their infant's hypoplastic left heart syndrome and were assisted by the support
      and sensitivity of staff or had discovered other resources. CONCLUSIONS: All
      parents of surviving infants with hypoplastic left heart syndrome in PICU,
      irrespective of timing of diagnosis, experienced numerous stresses and losses,
      and the majority exhibited clinical levels of traumatic stress. Receiving the
      diagnosis itself is very traumatic and is compounded by the environment of the
      PICU which alienates parents from their infants and interferes with parent-infant
      bonding. Parental adaptation to this situation can be assisted by staff.

PMID- 23965636
TI  - Patterns of medication exposures in hospitalized pediatric patients with acute
      renal failure requiring intermittent or continuous hemodialysis.
AB  - OBJECTIVES: Care for the pediatric patient with acute renal failure who requires
      hemodialysis (including continuous renal replacement therapy) is made more
      complex, as this intervention may significantly affect drug clearance,
      potentially altering, to a degree that is largely unknown, the effectiveness and
      safety of the multiple medications used to manage this complex patient
      population. This study aims to describe patterns of drug utilization among a
      large cohort of pediatric patients requiring hemodialysis and to document the
      easily accessible existing data available for dosing guidance of frequently
      prescribed medications. STUDY DESIGN: Retrospective cohort using the Pediatric
      Health Information System database. SETTING: Forty freestanding children's
      hospitals throughout the United States. PATIENTS: Two thousand seven hundred
      thirty-eight pediatric patients with acute renal failure treated with
      hemodialysis from 2007 to 2011. INTERVENTION: A retrospective review of all
      patients requiring hemodialysis from 2007 to 2011 was conduction using the
      Pediatric Health Information System Database. MAIN RESULTS: Over 6% of pediatric
      patients with acute renal failure treated with hemodialysis were exposed to
      hemodialysis for over 2 weeks. Cumulative exposure to distinct drugs increased
      substantially with more prolonged courses of hemodialysis. Of the 50 most
      frequently prescribed medications in the cohort with acute renal failure treated
      with hemodialysis, 10% have readily available and easily accessible information
      to guide dosing adjustments with the use of hemodialysis. Furthermore, only 18%
      of these medications have clear recommendations for dosing in pediatric patients
      of all age groups with renal failure. CONCLUSIONS: Pediatric patients with acute
      renal failure managed with hemodialysis are exposed to a broad variety of
      medications, with a high prevalence of polypharmacy. There is a trend for longer
      courses of hemodialysis in these patients, which leads to an increase in
      cumulative drug exposure, complexity of drug interactions, and potential
      toxicity. For the vast majority of medications that are being used to treat this
      complex patient population, pediatric dosing guidance is not easily accessible.
      These findings underscore the need for targeted pharmacologic studies of
      medications used in the pediatric population managed with hemodialysis.

PMID- 23965637
TI  - Continuous renal replacement therapy with an automated monitor is superior to a
      free-flow system during extracorporeal life support.
AB  - OBJECTIVES: To determine whether integrated continuous renal replacement therapy
      provides more accurate fluid management than IV pump free-flow ultrafiltration in
      pediatric patients on extracorporeal life support. DESIGN: Retrospective study.
      SETTING: PICU and neonatal ICU in a tertiary academic center. PATIENTS: Infants
      and children less than 18 years old. INTERVENTIONS: Extracorporeal membrane
      oxygenation and continuous renal replacement therapy. MEASUREMENTS AND MAIN
      RESULTS: Clinical data collected on patients who received free-flow or integrated
      renal replacement therapy while on extracorporeal life support. Normalized
      ultrafiltration error was calculated as: (physician specified fluid loss per 24
      hr period - actual fluid loss per 24-hr period) divided by patient body weight
      (kg). Mixed linear regression analyses were used to model longitudinal
      ultrafiltration error trajectories within each mode of ultrafiltration. Based on
      an analysis of 458 serial ultrafiltration fluid balance measurements, integrated
      ultrafiltration was significantly more accurate than free-flow ultrafiltration
      (normalized ultrafiltration error of 1.2 vs 13.1 mL; p < 0.001). After adjusting
      for patient factors and time, integrated ultrafiltration was associated with a
      significantly lower normalized ultrafiltration error (variable estimate, -24 +/-
      6; p < 0.001). The use of integrated ultrafiltration was associated with shorter
      duration of extracorporeal life support (384 vs 583 hr, p < 0.001) and renal
      replacement therapy (185 vs 477 hr, p < 0.001) than free-flow patients. Overall
      ICU and hospital length of stay and in-hospital mortality were similar between
      the groups. CONCLUSIONS: While free-flow ultrafiltration has the advantages of
      simplicity and low cost, integrated renal replacement therapy provides more
      accurate fluid management during extracorporeal life support. Better fluid status
      management with integrated renal replacement therapy may contribute to shorter
      duration of extracorporeal life support.

PMID- 23965638
TI  - Probiotic use and prevalence of candidemia and candiduria in a PICU.
AB  - OBJECTIVES: To compare the prevalence of candidemia and candiduria before and
      after the introduction of routine use of probiotics in children who received
      broad-spectrum antibiotics in a PICU. DESIGN: Retrospective "before and after"
      study. SETTING: A 12-bed PICU of a teaching hospital in India. PATIENTS: Children
      3 months to 12 years old, admitted to the PICU over two 9 months' time periods,
      who received broad-spectrum antibiotics for more than 48 hours. INTERVENTIONS:
      Three hundred forty-four patients enrolled between November 2008 and July 2009
      after the introduction of routine use of probiotics served as the "probiotic
      group"; they had received one sachet twice a day of a probiotic mix (EUGI
      [Wallace Pharma, Goa, India] containing Lactobacillus acidophillus, Lactobacillus
      rhamnosum, Bifidobacterium longum, Bifidobacterium bifidum, Saccharomyces
      boulardii, and Streptococcus thermophilus) for 7 days. Three hundred seventy-six
      children enrolled between February 2007 and October 2007 served as "controls."
      Blood was sent for bacterial and fungal cultures if clinically indicated and
      urine catheter/bag specimen was submitted for bacterial and fungal culture twice
      a week as per unit's protocol. MEASUREMENTS AND MAIN RESULTS: Primary outcome was
      growth of Candida in blood (candidemia), and secondary outcomes were growth of
      Candida in urine (candiduria), nosocomial bloodstream infections, and urinary
      tract infections. Data were retrieved from the case records. Candidemia was seen
      in four of 344 patients (1.2%) in the probiotic group and in 14 of 376 (3.7%) in
      the control group (relative risk, 0.31; 95% CI, 0.10-0.94; p = 0.03). Candiduria
      was noted in 37 of 344 patients (10.7%) in the probiotic group and 83 of 376
      (22%) in the control group (relative risk, 0.48; 95% CI, 0.34-0.7; p = 0.0001).
      The prevalence of nosocomial bloodstream infection and urinary tract infection in
      the probiotic and control groups was 20.3% and 26% (p = 0.07) and 14.2% and 19.1%
      (p = 0.08), respectively. CONCLUSIONS: Routine use of a mix of probiotics in
      patients who receive broad-spectrum antibiotics could be a useful strategy to
      reduce the prevalence of candidemia and candiduria in the PICU.

PMID- 23965639
TI  - Ventilated cookstoves associated with improvements in respiratory health-related
      quality of life in rural Bolivia.
AB  - BACKGROUND: Household air pollution (HAP) from combustion of biomass fuels
      worldwide is linked to asthma, respiratory infections and chronic pulmonary
      diseases. Implementation of ventilated cookstoves significantly reduces exposure
      to HAP. However, improvements in concurrent respiratory health-related quality of
      life (HRQoL) have not been previously evaluated with a standardized
      questionnaire. METHODS: The association between woodsmoke exposure and
      respiratory HRQoL outcomes was evaluated using an intervention study in a rural
      community in Bolivia. Indoor carbon monoxide (CO) levels from traditional stoves
      and from cookstoves with chimneys were analyzed alongside interview results of
      women heads-of-households using the St. George's Respiratory Questionnaire (SGRQ)
      in 2009 and 1-year post-intervention. RESULTS: Pronounced improvements in
      respiratory HRQoL and significant reductions of household CO levels followed
      installation of ventilated cookstoves. Stove implementation yielded lower indoor
      CO values and correlated positively with improved SGRQ scores. CONCLUSIONS: This
      is the first use of a standardized respiratory HRQoL assessment to determine the
      impact of ventilated cookstove implementation on reducing HAP. This preliminary
      study utilizes the SGRQ as a valuable tool enabling analysis of these health
      effects in relation to other respiratory disease states.

PMID- 23965641
TI  - Contagion: a misnomer for financial crisis.

PMID- 23965640
TI  - A review of economic evaluations of behavior change interventions: setting an
      agenda for research methods and practice.
AB  - BACKGROUND: The objective of this study was to review methodological quality of
      economic evaluations of lifestyle behavior change interventions (LBCIs) and to
      examine how they address methodological challenges for public health economic
      evaluation identified in the literature. METHODS: Pubmed and the NHS economic
      evaluation database were searched for published studies in six key areas for
      behavior change: smoking, physical activity, dietary behavior, (illegal) drug
      use, alcohol use and sexual behavior. From included studies (n = 142), we
      extracted data on general study characteristics, characteristics of the LBCIs,
      methodological quality and handling of methodological challenges. RESULTS:
      Economic evaluation evidence for LBCIs showed a number of weaknesses: methods,
      study design and characteristics of evaluated interventions were not well
      reported; methodological quality showed several shortcomings and progress with
      addressing methodological challenges remained limited. CONCLUSIONS: Based on the
      findings of this review we propose an agenda for improving future evidence to
      support decision-making. Recommendations for practice include improving reporting
      of essential study details and increasing adherence with good practice standards.
      Recommendations for research methods focus on mapping out complex causal pathways
      for modeling, developing measures to capture broader domains of wellbeing and
      community outcomes, testing methods for considering equity, identifying relevant
      non-health sector costs and advancing methods for evidence synthesis.

PMID- 23965642
TI  - Contagion: epidemiological models and financial crises.
AB  - Since the 1990s, economists have drawn on the epidemiology of emerging infectious
      diseases to explain the diffusion of shock through an increasingly complex
      financial system. The successful coordination of public health responses to
      disease threats, and in particular the epidemiological modelling underpinning
      infection control, has influenced economists' understanding of the risks posed to
      the stability of the financial system by 'contagion'. While the exportation of
      analytic models and frames of reference can be fruitful, reinvigorating the
      destination domain, such analogizing can have a distorting effect. There are
      differences between biological and financial systems. Moreover, the migration of
      highly context-specific epidemiological models may undermine the basis of the
      analogy. Finally, there may be repercussions for the efficacy of public health in
      the way that its aims are misconstrued in financial analyses. 

PMID- 23965643
TI  - Comment on Peckham: contagion-epidemiological models and financial crises.

PMID- 23965645
TI  - Development of a pharmacokinetic interaction model for co-administration of
      simvastatin and amlodipine.
AB  - A model for drug interaction between amlodipine and simvastatin was developed
      using concentration data obtained from a multiple-dose study consisting of single
      and co-administration of amlodipine and simvastatin conducted in healthy
      Koreans. Amlodipine concentrations were assumed to influence the clearance of
      simvastatin and simvastatin acid, which as well as the oral bioavailability was
      allowed to vary depending on genetic polymorphisms of metabolic enzymes.
      Covariate effects on drug concentrations were also considered. The developed
      model yielded a 46% increase in simvastatin bioavailability and a 13% decrease in
      simvastatin clearance when amlodipine 10 mg was co-administered. When CYP3A4/5
      polymorphisms were assessed by a mixture model, extensive metabolizers yielded a
      decrease in simvastatin bioavailability of 81% and a decrease in simvastatin
      clearance by 4.6 times as compared to poor metabolizers. Sixty percent of the
      usual dose was the optimal simvastatin dose that can minimize the interaction
      with amlodipine 10 mg. Age and weight had significant effects on amlodipine
      concentrations. In conclusion, this study has quantitatively described the
      pharmacokinetic interaction between simvastatin and amlodipine using a modeling
      approach. Given that the two drugs are often prescribed together, the developed
      model is expected to contribute to more efficient and safer drug treatment when
      they are co-administered.

PMID- 23965646
TI  - Prescription-compounding with manufactured products.
AB  - Abstract not available. 

PMID- 23965644
TI  - Differences in the glucuronidation of resveratrol and pterostilbene: altered
      enzyme specificity and potential gender differences.
AB  - Resveratrol, a natural polyphenol found in grapes, berries and other plants, has
      been proposed as an ideal chemopreventative agent due to its plethora of health
      promoting activities. However, despite its lofty promise as a cancer prevention
      agent its success in human clinical trials has been limited due to its poor
      bioavailability. Thus, interest in other natural polyphenols is intensifying
      including the naturally occurring dimethylated analog of resveratrol,
      pterostilbene. The UDP-glucuronosyltransferase (UGT) family of enzymes plays a
      vital role in the metabolism of both resveratrol and pterostilbene. The current
      study sought to elucidate the UGT family members responsible for the metabolism
      of pterostilbene and to examine gender differences in the glucuronidation of
      resveratrol and pterostilbene. We demonstrate that UGT1A1 and UGT1A3 are mainly
      responsible for pterostilbene glucuronidation although UGT1A8, UGT1A9 and UGT1A10
      also had detectable activity. Intriguingly, UGT1A1 exhibits the highest activity
      against both resveratrol and pterostilbene despite altered hydroxyl group
      specificity. Using pooled human liver microsomes, enzyme kinetics were determined
      for pterostilbene and resveratrol glucuronides. In all cases females were more
      efficient than males, indicating potential gender differences in stilbene
      metabolism. Importantly, the glucuronidation of pterostilbene is much less
      efficient than that of resveratrol, indicating that pterostilbene will have
      dramatically decreased metabolism in humans.

PMID- 23965647
TI  - Home infusion: overcoming the barriers to entry.
AB  - The field of pharmacy service is evolving rapidly, as is the delivery of
      healthcare in general. From patients with infectious diseases dying because there
      was nothing available to fight the infections, to the involvement of an episodic
      based model of care with patients traversing inpatient- and outpatient-based
      delivery systems, to the new frontier of chronic care and with supports such as
      the one by the Centers for Disease Control that hospital-acquired infections are
      killing about 100,000 Americans every year, the home infusion business has become
      a major alternative to in-hospital treatment. This article discusses the barriers
      to entry into the home infusion business and assists in the evaluation of a home
      infusion reimbursement organization. 

PMID- 23965648
TI  - In the hands of your enemy.
AB  - In the days of the post 9/11 attacks in the United States and the response
      against terrorism, one must question whether the source and supply of medicines
      in America is safe and adequate. This article reviews a common thread that runs
      through the periods of national emergency brought on by war, beginning with the
      Revolutionary War and repeated in the Civil War, World War 1, and World War 2:
      access to sufficient safe medicines. The shortage of medicines challenged the
      birth of the new nation in the Revolutionary War and helped thwart its
      destruction by the withdrawal of the southern states in the Civil War. Similarly,
      access to natural medicine and patented synthetic chemicals created major
      challenges in both World War 1 and World War 2. While not the only factor in
      victory, medicines did play an important role. Two separate but intertwined
      questions are evident. The first is whether the United States can control and
      provide the supply of medicines needed for the health and safety of it citizens
      military and civilian. The second is whether the quality, that is the safety and
      efficacy, can be assured whether the source of the medicine is domestic or
      imported. 

PMID- 23965649
TI  - The clinical use of dehydroepiandrosterone in postmenopausal women.
AB  - A basic understanding of the distinct metabolism, mechanism of action, and
      clinical use of dehydroepiandrosterone and its metabolites is critical to
      balancing the hormone milieu in postmenopausal women. To date, studies of
      dehydroepiandrosterone therapy in women with adrenal insufficiency suggest that
      they are the most likely group to gain health benefits from
      dehydroepiandrosterone replacement therapy. Our understanding of the potential
      long-term health benefits of replacing dehydroepiandrosterone along with other
      deficient hormones is still only in its infancy. With the evidence currently
      available, however, one can reasonably suggest that dehydroepiandrosterone offers
      the promise of a safe and efficient replacement therapy for specific symptoms
      common to postmenopausal women. This article reviews the metabolism, physiology,
      and clinical use of dehydroepiandrosterone in postmenopausal women. The clinical
      effectiveness of dehydroepiandrosterone for vulvovaginal atrophy, sexual
      dysfunction, osteoporosis, adrenal and immunological function, cardiovascular
      disease, and, in combination, hormone replacement therapy is reviewed. In
      addition, the use of the dehydroepiandrosterone metabolite 7-keto
      dehydroepiandrosterone for weight loss is discussed. 

PMID- 23965650
TI  - Extemporaneous compounding of medicated ointments.
AB  - Topical preparations represent a large percentage of compounded prescriptions,
      particularly in the area of dermatology. Properties of ointment bases vary
      greatly, and active ingredients are frequently added as aqueous or alcoholic
      solutions. Currently, there are no quantitative guidelines stating the various
      water and alcohol absorption capacity of different bases. A short experiment was
      designed to quantitate the amount of water or alcohol that could be absorbed by a
      series of ointment bases of varying types. Our findings may be used to assist
      compounding pharmacists in deciding what base is most suitable to use when
      considering the amount of water, alcohol, or any similar solvent needed to
      compound the preparation. A general overview of issues related to topical
      medication compounding is also provided in this article. 

PMID- 23965651
TI  - "My hip hurts": a collaboration of clinicians in the treatment of adhesive
      capsulitis to optimize patient care.
AB  - In order to achieve a positive outcome for individuals who are diagnosed with a
      "frozen joint" or adhesive capsulitits, a collaborative relationship among
      clinicians provides support and communication. The relationship should include
      the physical therapist, physician, and the pharmacist. Capsulitis, or capsular
      restriction, is often treated with anti-inflammatory agents, localized steroidal
      injections, directed physical therapy, or orthopedic visual inspection. The
      professional judgments of coordinating healthcare practitioners provide for
      assessments and plans that result in favorable outcomes with optimized recovery
      time. 

PMID- 23965652
TI  - All-purpose nipple ointment: a compounding solution to common problems with
      breastfeeding.
AB  - Breastfeeding is readily accepted as the ideal source of infant nutrition for
      healthy growth and development. There are, however, many factors that lead to a
      mother's decision to discontinue breastfeeding. The most commonly reported
      problem is sore or painful nipples. It is essential that the healthcare team not
      only understands the obstacles associated with continued breastfeeding, but also
      work together to overcome them. Through the preparation of "all-purpose nipple
      ointment" and patient education, compounding pharmacists can do their part as
      essential members of the healthcare team and provide a pharmaceutical therapy for
      one of the major causes of breastfeeding discontinuance. 

PMID- 23965653
TI  - Case report: management of secondary hypertension in a feline with the use of
      transdermal prazosin.
AB  - Case reports, which are a report of a patient's symptoms, diagnosis treatment,
      and follow up, offer great assistance to a practitioner and compounding
      pharmacist in the oftentimes "trial and error" procedures of treating a patient
      that presents with a hard-to-treat diagnosed with hypertension secondary to
      polycstic kidney disease. 

PMID- 23965654
TI  - Quality-control analytical methods: endotoxins: essential testing for pyrogens in
      the compounding laboratory, part2.
AB  - Ensuring that the endotoxin burden in sterile preparations is within allowable
      limits is one of the greatest challenges faced by compounding pharmacists. Today,
      endotoxin analyses can be performed in the pharmacy with a test kit or
      accomplished by sending samples to a contract testing laboratory. Both types of
      screening are discussed in this article, and information that enables compounders
      to determine the preferred method of endotoxin testing is provided. A brief
      history of endotoxin testing is presented, and the advantages and disadvantages
      of pyrogen screening with either an in-house test kit or the services of a
      contract testing laboratory are explored. Accurate screening for pyrogens ensures
      that only sterile formulations containing a safe level of endotoxins are
      dispensed. An essential task in sterile compounding, endotoxin testing safeguards
      patients against the morbidity and mortality that can result from treatment with
      a contamination preparation. 

PMID- 23965655
TI  - Basics of compounding: basics of compounding with aliquots, dilutions, and
      concentrates.
AB  - Pharmacists involved in Compounding must consider a number of factors when
      determining the actual quantity of an active ingredient to use for a compounded
      prescription. Many drug substances and excipients are available as aliquots,
      dilutions, and concentrates and do not consist of 100% drug or chemical. Since
      the bulk substance, or active pharmaceutical ingredient or excipient is not 100%
      active drug in all cases, then it is important to know the strength of the item
      so that appropriate allowances can be made to obtain the correct amount. 

PMID- 23965656
TI  - Stability of methimazole in poloxamer lecithin organogel to determine beyond-use
      date.
AB  - The purpose of this stability study was to determine the beyond-use date of the
      active ingredient methimazole extemporaneously prepared for transdermal
      absorption to treat feline hyperthyroidism. The methimazole was prepared in
      poloxamer lecithin organogel and subjected to a three-month stability study. It
      was determined that under room temperature conditions (25 degrees Celsius +/- 2
      degrees/60% RH +/- 5%) the methimazole concentration remained above 90% after 62
      days. An accelerated condition of 35 degrees Celsius and refrigerated condition
      of 5 degrees Celsius were also employed to see how temperature affected the
      stability of the drug. Under all three conditions the methimazole concentration
      dropped below 90% after day 62. It was observed that the refrigerated conditions
      appeared to be least stable both physically and chemically. A control sample was
      also prepared, stored, and packaged similarly to the sample preparations. As a
      result, the beyond-use date was determined to be 60 days at room temperature. The
      drug preparation should not be stored in a refrigerated condition. 

PMID- 23965657
TI  - Barrier isolator/glovebox glove dexterity study.
AB  - In response to new, stricter safety requirements set out by the federal
      government, compounding pharmacists are investigating applications and processes
      appropriate for their facilities. One application, currently used by many
      industries, was developed by Los Alamos National Laboratories in the early days
      of defense work. A barrier isolator or "glovebox" is a containment device that
      allows work within a sealed space while providing protection for people and the
      environment. The operations at Plutonium Facility (TA-55) in Los Alamos National
      Laboratories involve various amounts of plutonium. Gloveboxes are used to handle
      plutonium, and glovebox gloves are the weakest part of this engineering control.
      Currently a lead-loaded glove made from Hypalon is used. The lead-loaded gloves
      are compared to unleaded gloves with respect to dexterity and its effect on the
      outcome of any task performance. Experiments have been conducted on two models of
      unleaded gloves (15-mil thick Hypalon gloves and 30-mil thick Hypalon gloves), as
      well as 30-mil thick lead-loaded gloves. The objective of this research is to
      study the effect of lead-loaded gloves versus unleaded gloves on task
      performance. We use inferential statistical analysis of this data to support
      scientific judgment of the probability that the observed difference between
      tested gloves is dependable or that any difference noted might have happened by
      chance. 

PMID- 23965659
TI  - Surface transfer doping can mediate both colloidal stability and self-assembly of
      nanodiamonds.
AB  - Although undoped diamond is insulating, hydrogenated bulk diamond surfaces
      exhibit surface conductivity under air and are electrochemically active in
      aqueous solutions. Due to their large surface/volume ratio, similar surface
      effects may exhibit a dramatic impact on the properties of nanodiamonds. Here we
      show that plasma-hydrogenated detonation nanodiamonds (NDs-H) display a positive
      zeta potential in water due to charge transfer with a redox couple involving
      oxygen in water. The transfer doping of NDs-H in water can be modulated by pH.
      Surprisingly, after acid addition, strong Coulomb coupling between NDs-H and
      adsorbed counterions induces the self-assembly of NDs-H into organized macro
      structures reaching millimeter scale. 

PMID- 23965658
TI  - Independent predictors of enteric fistula and abdominal sepsis after damage
      control laparotomy: results from the prospective AAST Open Abdomen registry.
AB  - IMPORTANCE: Enterocutaneous fistula (ECF), enteroatmospheric fistula (EAF), and
      intra-abdominal sepsis/abscess (IAS) are major challenges for surgeons caring for
      patients undergoing damage control laparotomy after trauma. OBJECTIVE: To
      determine independent predictors of ECF, EAF, or IAS in patients undergoing
      damage control laparotomy after trauma, using the AAST Open Abdomen Registry.
      DESIGN: The AAST Open Abdomen registry of patients with an open abdomen following
      damage control laparotomy was used to identify patients who developed ECF, EAF,
      or IAS and to compare these patients with those without these complications.
      Univariate analyses were performed to compare these groups of patients. Variables
      from univariate analyses differing at P < .20 were entered into a stepwise
      logistic regression model to identify independent risk factors for ECF, EAF, or
      IAS. SETTING: Fourteen level I trauma centers. PARTICIPANTS: A total of 517
      patients with an open abdomen following damage control laparotomy. MAIN OUTCOMES
      AND MEASURES: Complication of ECF, EAF, or IAS. RESULTS: More patients in the
      ECF/EAF/IAS group than in the group without these complications underwent bowel
      resection (63 of 111 patients [57%] vs 133 of 406 patients [33%]; P < .001).
      Within the first 48 hours after surgery, the ECF/EAF/IAS group received more
      colloids (P < .03) and total fluids (P < .03) than did the group without these
      complications. The ECF/EAF/IAS group underwent almost twice as many abdominal
      reexplorations as did the group without these complications (mean [SD] number,
      4.1 [4.1] vs 2.2 [3.4]; P < .001). After multivariate analysis, the independent
      predictors of ECF/EAF/IAS were a large bowel resection (adjusted odds ratio
      [AOR], 3.56 [95% CI, 1.88-6.76]; P < .001), a total fluid intake at 48 hours of
      between 5 and 10 L (AOR, 2.11 [95% CI, 1.15-3.88]; P = .02) or more than 10 L
      (AOR, 1.93 [95% CI, 1.04-3.57]; P = .04), and an increasing number of
      reexplorations (AOR, 1.14 [95% CI, 1.06-1.21]; P < .001). CONCLUSIONS AND
      RELEVANCE: Large bowel resection, large-volume fluid resuscitation, and an
      increasing number of abdominal reexplorations were statistically significant
      predictors of ECF, EAF, or IAS in patients with an open abdomen after damage
      control laparotomy.

PMID- 23965661
TI  - Delayed graft function in living donor kidney transplantation.

PMID- 23965660
TI  - Vitrification of day 3 cleavage-stage embryos yields better clinical outcome in
      comparison with vitrification of day 2 cleavage-stage embryos.
AB  - The objective of this retrospective study was to determine an optimal time point
      for vitrification of cleavage-stage human embryos. This study included patients
      who were undergoing day 2 or day 3 vitrified-warmed cleavage-stage embryo
      transfer at the In Vitro Fertilization (IVF) Programme of the Shanghai First
      Maternity and Infant Hospital, China, affiliated to the Tongji University School
      of Medicine, from April 2010 to March 2012. Intervention was made for the entire
      cohort of vitrified embryos for poor responder patients so as to avoid severe
      ovarian hyperstimulation syndrome. Embryo survival rate (SR) after vitrification
      warming, implantation rate (IR), and clinical pregnancy rate (CPR) were the main
      outcome measurements. In total, 380 vitrified-warmed cleavage-stage embryo
      transfer (VWT) cycles were included. We found that the SR after vitrification and
      warming for day 2 embryos and day 3 embryos were 92.7% and 92.8%, respectively.
      For poor ovarian responders, the IR of day 2 and day 3 vitrified-warmed embryos
      was 6.4% and 13.2%, respectively (P = 0.186). The CPR for day 3 vitrified-warmed
      embryos was significantly higher than that of day 2 vitrified-warmed embryos
      (17.6 vs. 4.0% per transfer cycle, P = 0.036). For patients who had their entire
      cohort of embryos vitrified to prevent severe ovarian hyperstimulation syndrome
      (OHSS), the IR and CPR were not significantly different for day 2 and day 3
      vitrified-warmed embryo transfer. In conclusion, for vitrified-warmed embryo
      transfer, cryopreservation of the entire cohort of embryos on day 3 resulted in
      better clinical outcomes compared with cryopreservation on day 2. Therefore, it
      is highly recommended that cleavage-stage embryos should be vitrified on day 3,
      but not on day 2, particularly for poor ovarian responder patients.

PMID- 23965662
TI  - Take a number.

PMID- 23965668
TI  - Polycyclic hydrocarbons: Nanographenes do the twist.

PMID- 23965669
TI  - Site-selective reactions: Exploiting intramolecularity.

PMID- 23965670
TI  - Self-assembly: Micelles grow more complex.

PMID- 23965671
TI  - Low-temperature reactions: Tunnelling in space.

PMID- 23965672
TI  - C-H bond functionalization: An aminated reaction.

PMID- 23965674
TI  - A grossly warped nanographene and the consequences of multiple odd-membered-ring
      defects.
AB  - Graphite, the most stable form of elemental carbon, consists of pure carbon
      sheets stacked upon one another like reams of paper. Individual sheets, known as
      graphene, prefer planar geometries as a consequence of the hexagonal honeycomb
      like arrangements of trigonal carbon atoms that comprise their two-dimensional
      networks. Defects in the form of non-hexagonal rings in such networks cause
      distortions away from planarity. Herein we report an extreme example of this
      phenomenon. A 26-ring C80H30 nanographene that incorporates five seven-membered
      rings and one five-membered ring embedded in a hexagonal lattice was synthesized
      by stepwise chemical methods, isolated, purified and fully characterized
      spectroscopically. Its grossly warped structure was revealed by single-crystal X
      ray crystallography. An independent synthetic route to a freely soluble
      derivative of this new type of 'nanocarbon' is also reported. Experimental data
      reveal how the properties of such a large graphene subunit are affected by
      multiple odd-membered-ring defects. 

PMID- 23965675
TI  - Accelerated chemistry in the reaction between the hydroxyl radical and methanol
      at interstellar temperatures facilitated by tunnelling.
AB  - Understanding the abundances of molecules in dense interstellar clouds requires
      knowledge of the rates of gas-phase reactions between uncharged species. However,
      because of the low temperatures within these clouds, reactions with an activation
      barrier were considered too slow to play an important role. Here we show that,
      despite the presence of a barrier, the rate coefficient for the reaction between
      the hydroxyl radical (OH) and methanol--one of the most abundant organic
      molecules in space--is almost two orders of magnitude larger at 63 K than
      previously measured at ~200 K. We also observe the formation of the methoxy
      radical product, which was recently detected in space. These results are
      interpreted by the formation of a hydrogen-bonded complex that is sufficiently
      long-lived to undergo quantum-mechanical tunnelling to form products. We
      postulate that this tunnelling mechanism for the oxidation of organic molecules
      by OH is widespread in low-temperature interstellar environments.

PMID- 23965676
TI  - Photochemical activity of a key donor-acceptor complex can drive stereoselective
      catalytic alpha-alkylation of aldehydes.
AB  - Asymmetric catalytic variants of sunlight-driven photochemical processes hold
      extraordinary potential for the sustainable preparation of chiral molecules.
      However, the involvement of short-lived electronically excited states inherent to
      any photochemical reaction makes it challenging for a chiral catalyst to dictate
      the stereochemistry of the products. Here, we report that readily available
      chiral organic catalysts, with well-known utility in thermal asymmetric
      processes, can also confer a high level of stereocontrol in synthetically
      relevant intermolecular carbon-carbon bond-forming reactions driven by visible
      light. A unique mechanism of catalysis is proposed, wherein the catalyst is
      involved actively in both the photochemical activation of the substrates (by
      inducing the transient formation of chiral electron donor-acceptor complexes) and
      the stereoselectivity-defining event. We use this approach to enable
      transformations that are extremely difficult under thermal conditions, such as
      the asymmetric alpha-alkylation of aldehydes with alkyl halides, the formation of
      all-carbon quaternary stereocentres and the control of remote stereochemistry. 

PMID- 23965677
TI  - Mechanochemical strengthening of a synthetic polymer in response to typically
      destructive shear forces.
AB  - High shear stresses are known to trigger destructive bond-scission reactions in
      polymers. Recent work has shown that the same shear forces can be used to
      accelerate non-destructive reactions in mechanophores along polymer backbones,
      and it is demonstrated here that such mechanochemical reactions can be used to
      strengthen a polymer subjected to otherwise destructive shear forces.
      Polybutadiene was functionalized with dibromocyclopropane mechanophores, whose
      mechanical activation generates allylic bromides that are crosslinked in situ by
      nucleophilic substitution reactions with carboxylates. The crosslinking is
      activated efficiently by shear forces both in solvated systems and in bulk
      materials, and the resulting covalent polymer networks possess moduli that are
      orders-of-magnitude greater than those of the unactivated polymers. These
      molecular-level responses and their impact on polymer properties have
      implications for the design of materials that, like biological materials,
      actively remodel locally as a function of their physical environment. 

PMID- 23965678
TI  - Sub-angstrom-resolution crystallography reveals physical distortions that enhance
      reactivity of a covalent enzymatic intermediate.
AB  - It is recognized widely that enzymes promote reactions by providing a pathway
      that proceeds through a transition state of lower energy. In principle, further
      rate enhancements could be achieved if intermediates are prevented from relaxing
      to their lowest energy state, and thereby reduce the barrier to the subsequent
      transition state. Here, we report sub-angstrom-resolution crystal structures of
      genuine covalent reaction intermediates of transketolase. These structures reveal
      a pronounced out-of-plane distortion of over 20 degrees  for the covalent bond
      that links cofactor and substrate, and a specific elongation of the scissile
      substrate carbon-carbon bond (d > 1.6 A). To achieve these distortions, the
      protein's conformation appears to prevent relaxation of a substrate-cofactor
      intermediate. The results implicate a reduced barrier to the subsequent step that
      is consistent with an intermediate of raised energy and leads to a more efficient
      overall process. 

PMID- 23965679
TI  - Enantioselective silyl protection of alcohols promoted by a combination of chiral
      and achiral Lewis basic catalysts.
AB  - Catalytic enantioselective monosilylations of diols and polyols furnish valuable
      alcohol-containing molecules in high enantiomeric purity. These transformations,
      however, require high catalyst loadings (20-30 mol%) and long reaction times (2-5
      days). Here, we report that a counterintuitive strategy involving the use of an
      achiral co-catalyst structurally similar to the chiral catalyst provides an
      effective solution to this problem. A combination of seemingly competitive Lewis
      basic molecules can function in concert such that one serves as an achiral
      nucleophilic promoter and the other performs as a chiral Bronsted base. On the
      addition of 7.5-20 mol% of a commercially available N-heterocycle (5
      ethylthiotetrazole), reactions typically proceed within one hour, and deliver the
      desired products in high yields and enantiomeric ratios. In some instances, there
      is no reaction in the absence of the achiral base, yet the presence of the
      achiral co-catalyst gives rise to facile formation of products in high
      enantiomeric purity. 

PMID- 23965680
TI  - Exceptional oxidation activity with size-controlled supported gold clusters of
      low atomicity.
AB  - The catalytic activity of gold depends on particle size, with the reactivity
      increasing as the particle diameter decreases. However, investigations into
      behaviour in the subnanometre regime (where gold exists as small clusters of a
      few atoms) began only recently with advances in synthesis and characterization
      techniques. Here we report an easy method to prepare isolated gold atoms
      supported on functionalized carbon nanotubes and their performance in the
      oxidation of thiophenol with O2. We show that single gold atoms are not active,
      but they aggregate under reaction conditions into gold clusters of low atomicity
      that exhibit a catalytic activity comparable to that of sulfhydryl oxidase
      enzymes. When clusters grow into larger nanoparticles, catalyst activity drops to
      zero. Theoretical calculations show that gold clusters are able to activate
      thiophenol and O2 simultaneously, and larger nanoparticles are passivated by
      strongly adsorbed thiolates. The combination of both reactants activation and
      facile product desorption makes gold clusters excellent catalysts. 

PMID- 23965681
TI  - Conditionally fluorescent molecular probes for detecting single base changes in
      double-stranded DNA.
AB  - Small variations in nucleic acid sequences can have far-reaching phenotypic
      consequences. Reliably distinguishing closely related sequences is therefore
      important for research and clinical applications. Here, we demonstrate that
      conditionally fluorescent DNA probes are capable of distinguishing variations of
      a single base in a stretch of target DNA. These probes use a novel programmable
      mechanism in which each single nucleotide polymorphism generates two
      thermodynamically destabilizing mismatch bubbles rather than the single mismatch
      formed during typical hybridization-based assays. Up to a 12,000-fold excess of a
      target that contains a single nucleotide polymorphism is required to generate the
      same fluorescence as one equivalent of the intended target, and detection works
      reliably over a wide range of conditions. Using these probes we detected point
      mutations in a 198 base-pair subsequence of the Escherichia coli rpoB gene. That
      our probes are constructed from multiple oligonucleotides circumvents synthesis
      limitations and enables long continuous DNA sequences to be probed. 

PMID- 23965682
TI  - Catalyst recognition of cis-1,2-diols enables site-selective functionalization of
      complex molecules.
AB  - Carbohydrates and natural products serve essential roles in nature, and also
      provide core scaffolds for pharmaceutical agents and vaccines. However, the
      inherent complexity of these molecules imposes significant synthetic hurdles for
      their selective functionalization and derivatization. Nature has, in part,
      addressed these issues by employing enzymes that are able to orient and activate
      substrates within a chiral pocket, which increases dramatically both the rate and
      selectivity of organic transformations. In this article we show that similar
      proximity effects can be utilized in the context of synthetic catalysts to
      achieve general and predictable site-selective functionalization of complex
      molecules. Unlike enzymes, our catalysts apply a single reversible covalent bond
      to recognize and bind to specific functional group displays within substrates. By
      combining this unique binding selectivity and asymmetric catalysis, we are able
      to modify the less reactive axial positions within monosaccharides and natural
      products. 

PMID- 23965683
TI  - On the cooperative formation of non-hydrogen-bonded water at molecular
      hydrophobic interfaces.
AB  - The unique structural, dynamical and chemical properties of air/water and
      oil/water interfaces are thought to play a key role in various biological,
      geological and environmental processes. For example, non-hydrogen-bonded
      ('dangling') OH groups--which create surface defects in water's hydrogen bonding
      network and are experimentally detected at both macroscopic (air/water or
      oil/water) and microscopic (dissolved hydrophobic molecule) interfaces--are
      thought to catalyse some chemical reactions. However, how the size, curvature or
      charge of the exposed hydrophobic surface influences water's propensity to form
      dangling OH defects has not yet been established quantitatively. Here we use
      Raman multivariate curve resolution to probe spectroscopically the hydrophobic
      hydration shell and, using a statistical multisite analysis, we show that such
      interfacial dangling OH structures are entropically stabilized and their
      formation is cooperative (the probability that a non-hydrogen-bonded OH group
      will form depends nonlinearly on the hydrophobic surface area). We thus expose an
      important difference between the chemical properties of molecular and macroscopic
      oil/water interfaces.

PMID- 23965684
TI  - Recalling radon's recognition.

PMID- 23965686
TI  - OCT and NMO: are there methods to our madness?

PMID- 23965685
TI  - Fertilization ability of porcine oocytes reconstructed from ooplasmic fragments
      produced and characterized after serial centrifugations.
AB  - Mitochondria are reported to be critical in in vitro maturation of oocytes and
      subsequent embryo development after fertilization, but their contribution for
      fertilization has not been investigated in detail. In the present study, we
      investigate the contribution of mitochondria to fertilization using reconstructed
      porcine oocytes by fusion of ooplasmic fragments produced by serial
      centrifugations (centri-fusion). Firstly, we evaluated the characteristics of
      ooplasmic fragments. Three types of fragments were obtained by centrifugation of
      porcine oocytes matured in vitro for 46 h: brownish (B), transparent (T) and
      large (L) fragments containing both B and T parts in a fragment. The production
      efficiencies of these types of fragments were 71.7, 91.0 and 17.8 fragments/100
      oocytes, respectively. In experiments, L fragments were excluded because they
      contained both brownish and transparent components that were apparently
      intermediate between B and T fragments. Observations by confocal microscopy after
      staining with MitoTracker Red CMXRos(r) and transmission electron microscopy
      revealed highly condensed active mitochondria in B fragments in contrast to T
      fragments that contained only sparse organelles. We reconstructed oocytes by
      fusion of a karyoplast and two cytoplasts from B and T fragments (B and T
      oocytes, respectively). The B oocytes showed higher sperm penetration (95.8%) and
      male pronuclear formation rates (94.2%) by in vitro fertilization than T oocytes
      (66.7% and 50.0%, respectively). These results suggest that the active
      mitochondria in oocytes may be related to their ability for fertilization.

PMID- 23965687
TI  - Low prevalence of bilateral (presumed nutritional) optic neuropathy as a cause of
      blindness in the Gambia.
AB  - OBJECTIVE: Previous reports of epidemics of optic neuropathy in Africa have
      mainly focused on eastern and central areas. Our study aimed to measure the
      prevalence of optic neuropathy in The Gambia, a West African country, and compare
      this prevalence with a simultaneously occurring epidemic of optic neuropathy, now
      considered endemic, in Tanzania. METHODS: The sample population, derived from the
      Gambian National Blindness Survey (1996), was selected using simple random
      sampling. Thirty-three cases of low vision/blindness were identified where optic
      neuropathy was the sole cause of visual loss. Within a month, 31 cases were
      located and these patients underwent ophthalmic and peripheral nerve assessment
      and completed lifestyle questionnaires. RESULTS: Five of the 31 individuals were
      found to have bilateral symmetrical optic neuropathy. Although it was not
      possible to fully ascertain etiology, the phenotype is compatible with epidemic,
      presumed nutritional, optic neuropathy described in Tanzania. Comparative
      prevalence data suggest a prevalence of 0.07% in The Gambia based on a total
      sample size of 6873 vs 2.4% in Tanzania. CONCLUSION: Our data indicate that
      bilateral optic neuropathy is nonepidemic in The Gambia. Rare vitamin B12 and
      folate deficiencies reported in rural Gambians may explain the low prevalence
      because previous epidemics were due to nutrient deficiency. Our study is the only
      available estimate of epidemic optic neuropathy in The Gambia and, as such,
      provides an important contribution to our knowledge in identifying
      characteristics that may cause specific populations to be more susceptible to
      this public health burden.

PMID- 23965688
TI  - Restricted diffusion of the superior and inferior ophthalmic veins in cavernous
      sinus thrombosis.
AB  - Two previous reports have described restricted diffusion in thrombosed superior
      ophthalmic veins (SOVs) in patients with cavernous sinus thrombosis (CST). We
      report a patient who displayed restricted diffusion in both the SOV and inferior
      ophthalmic vein in CST consequent to a masticator space abscess. The orbital
      vascular imaging findings added support to the cavernous sinus findings in making
      the diagnosis of CST. Diffusion-weighted imaging of the orbit is a valuable asset
      in this setting.

PMID- 23965689
TI  - New and emerging interventional neuroradiologic techniques for neuro
      opthalmologic disorders.
AB  - BACKGROUND: A number of cerebrovascular disorders produce manifestations of neuro
      ophthalmologic significance. In many cases, these disorders can be treated using
      endovascular techniques. METHODS: The material in this article was obtained from
      a combination of personal experience and review of the literature using PubMed.
      RESULTS: A variety of new equipment, materials, and techniques are available to
      the interventional neuro-radiologist dealing with intracranial vascular lesions
      such as aneurysms, arteriovenous fistulas, and arteriovenous malformations.
      CONCLUSION: Physicians whose patients have intracranial vascular lesions should
      be aware of the endovascular options available for their patients.

PMID- 23965692
TI  - Neuro-ophthalmology in Israel.

PMID- 23965690
TI  - An elderly woman with difficulty reading and abnormal eye movements.

PMID- 23965693
TI  - A cost-utility analysis comparing the cost-effectiveness of simultaneous and
      staged bilateral total knee arthroplasty.
AB  - BACKGROUND: The safety and efficacy of simultaneous or staged bilateral total
      knee arthroplasty have long been debated among orthopaedic surgeons. Advocates
      for simultaneous bilateral total knee arthroplasty posit that the benefits of
      decreased costs and recovery time, with no difference in functional outcomes,
      outweigh the economic costs of potential complications. The purpose of the study
      was to conduct a cost-utility analysis comparing simultaneous bilateral total
      knee arthroplasty with staged bilateral total knee arthroplasty. METHODS: A
      Markov model was designed to compare the cost-effectiveness of simultaneous
      bilateral total knee arthroplasty with that of staged bilateral total knee
      arthroplasty. Nationwide Inpatient Sample data sets from 2004 to 2007 were used
      to identify 24,574 simultaneous and 382,496 unilateral procedures. On the basis
      of the codes of the International Classification of Diseases, Ninth Revision,
      Clinical Modification, perioperative complications were categorized as minor,
      major, and mortality, and respective probability values were calculated.
      Nationwide Inpatient Sample data were used to determine hospital costs
      conditional on procedure type and complications. Rehabilitation costs, anesthesia
      costs, and heath utilities were estimated from the literature. To minimize
      selection bias, propensity score matching was used to match the groups on
      comorbid conditions, socioeconomic variables, and hospital characteristics.
      RESULTS: Using the matched sample, all complication rates were higher for the
      staged group. The estimated mean cost (in 2012 U.S. dollars) was $43,401 for
      simultaneous bilateral total knee arthroplasty compared with $72,233 for staged
      bilateral total knee arthroplasty. The quality-adjusted life years gained were
      9.31 for simultaneous bilateral total knee arthroplasty and 9.29 for staged
      bilateral total knee arthroplasty. On the basis of these matched results,
      simultaneous bilateral total knee arthroplasty dominated staged bilateral total
      knee arthroplasty with lower costs and better outcomes. CONCLUSIONS: On the basis
      of this analysis, simultaneous bilateral total knee arthroplasty is more cost
      effective than staged bilateral total knee arthroplasty, with lower costs and
      better outcomes for the average patient. These data can inform shared medical
      decision-making when bilateral total knee arthroplasty is indicated.

PMID- 23965694
TI  - Mitigating adverse event reporting bias in spine surgery.
AB  - BACKGROUND: Recent articles in the lay press and literature have raised concerns
      about the ability to report honest adverse event data from industry-sponsored
      spine surgery studies. To address this, clinical trials may utilize an
      independent Clinical Events Committee (CEC) to review adverse events and
      readjudicate the severity and relatedness accordingly. We are aware of no prior
      study that has quantified either the degree to which investigator bias is present
      in adverse event reporting or the effect that an independent CEC has on
      mitigating this potential bias. METHODS: The coflex Investigational Device
      Exemption study is a prospective randomized controlled trial comparing coflex
      (Paradigm Spine) stabilization with lumbar spinal fusion to treat spinal stenosis
      and spondylolisthesis. Investigators classified the severity of adverse events
      (mild, moderate, or severe) and their relationship to the surgery and device
      (unrelated, unlikely, possibly, probably, or definitely). An independent CEC,
      composed of three spine surgeons without affiliation to the study sponsor,
      reviewed and reclassified all adverse event reports submitted by the
      investigators. RESULTS: The CEC reclassified the level of severity, relation to
      the surgery, and/or relation to the device in 394 (37.3%) of 1055 reported
      adverse events. The proportion of adverse events that underwent reclassification
      was similar in the coflex and fusion groups (37.9% compared with 36.0%, p =
      0.56). The CEC was 5.3 (95% confidence interval [CI], 2.6 to 10.7) times more
      likely to upgrade than downgrade the adverse event. The CEC was 7.3 (95% CI, 5.1
      to 10.6) times more likely to upgrade than downgrade the relationship to the
      surgery and 11.6 (95% CI, 7.5 to 18.8) times more likely to upgrade than
      downgrade the relationship to the device. The status of the investigator's
      financial interest in the company had little effect on the reclassification of
      adverse events. CONCLUSIONS: Thirty-seven percent of adverse events were
      reclassified by the CEC; the large majority of the reclassifications were an
      upgrade in the level of severity or a designation of greater relatedness to the
      surgery or device. CLINICAL RELEVANCE: An independent CEC can identify and
      mitigate potential inherent investigator bias and facilitate an accurate
      assessment of the safety profile of an investigational device, and a CEC should
      be considered a requisite component of future clinical trials.

PMID- 23965696
TI  - Nerve block of the infrapatellar branch of the saphenous nerve in knee
      arthroscopy: a prospective, double-blinded, randomized, placebo-controlled trial.
AB  - BACKGROUND: With the rising use of outpatient knee arthroscopy over the past
      decade, interest in peripheral nerve blocks during arthroscopy has increased.
      Femoral nerve blocks are effective but are associated with an inherent risk of
      the patient falling postoperatively because of quadriceps weakness. We studied
      blocks of the infrapatellar branch of the saphenous nerve, which produce
      analgesia in the knee that is similar to that resulting from a femoral nerve
      block but without associated quadriceps weakness. METHODS: Thirty-four patients
      were enrolled into each arm of this prospective, randomized, double-blinded trial
      comparing 10 mL of 0.25% bupivacaine used as a block of the infrapatellar branch
      of the saphenous nerve with a placebo during simple knee arthroscopy. Immediate
      outcome measures included Numeric Rating Scale (NRS) pain scores (0 to 10
      points), mobility and discharge times, opioid usage, subjective adverse side
      effects, and forty-eight-hour anesthesia recovery surveys. Short-term measures
      included one-week and twelve-week Lysholm knee scores. RESULTS: No adverse
      effects or increased quadriceps weakness were observed following use of the nerve
      block. Improvement in early NRS scores and subjective nausea (p = 0.03) were
      detected. Patients for whom the block was successful also had improved twelve
      week Lysholm knee scores (p = 0.04). No differences in opioid usage, mobility
      time, forty-eight-hour anesthesia recovery scores, or one-week Lysholm knee
      scores were found. CONCLUSIONS: No significant adverse effect or disadvantage was
      identified for blocks of the infrapatellar branch of the saphenous nerve used in
      simple knee arthroscopy. In addition to decreased early NRS scores and nausea,
      blocks of the infrapatellar branch of the saphenous nerve demonstrated potential
      benefit at twelve weeks after simple knee arthroscopy.

PMID- 23965695
TI  - Molecular characterization of articular cartilage from young adults with
      femoroacetabular impingement.
AB  - BACKGROUND: Femoroacetabular impingement is a frequent cause of hip pain and may
      lead to secondary osteoarthritis, yet little is known about the molecular events
      linking mechanical hip impingement and articular cartilage degeneration. The
      first goal of this study was to quantify the expression of inflammatory cytokine
      and chemokine, matrix-degrading, and extracellular matrix genes in articular
      cartilage harvested from control hips and hips with femoroacetabular impingement
      and end-stage osteoarthritis. The second goal was to analyze the relative
      expression of these genes in articular cartilage harvested at various stages of
      osteoarthritis. METHODS: Cartilage samples were obtained from thirty-two hips
      undergoing hip preservation surgery for femoroacetabular impingement or hip
      arthroplasty. Three control cartilage samples were also analyzed. Specimens were
      graded intraoperatively with regard to the severity of cartilage damage, the
      radiographic osteoarthritis grade was recorded, and quantitative RT-PCR (real
      time polymerase chain reaction) was performed to determine relative gene
      expression. RESULTS: Except for interleukin-1beta (IL-1beta) and CXCL2, the mRNA
      (messenger RNA) expression of all other chemokine (IL-8, CXCL1, CXCL3, CXCL6,
      CCL3, and CCL3L1), matrix-degrading (matrix metalloproteinase [MMP]-13 and ADAMTS
      4), and structural matrix (COL2A1 [collagen, type II, alpha] and ACAN [aggregan])
      genes was higher overall in cartilage from hips with femoroacetabular impingement
      compared with hips with osteoarthritis and normal controls. The differences
      reached significance (p <= 0.05) for seven of these ten quantified genes, with
      CXCL3, CXCL6, and COL2A1 being elevated in the femoroacetabular impingement group
      compared with only the control group and IL-8, CCL3L1, ADAMTS-4, and ACAN being
      elevated compared with both the osteoarthritis and control groups. When samples
      were grouped according to the stage of the degenerative cascade, mRNA expression
      was relatively higher in one of the two middle stages of femoroacetabular
      impingement (chondromalacia or cleavage/thinning), with the difference reaching
      significance for IL-8, CXCL2, CXCL3, CCL3L1, and ACAN. ACAN expression was
      diminished in hips with osteoarthritis compared with femoroacetabular impingement
      but elevated compared with the control articular cartilage. CONCLUSIONS:
      Articular cartilage from the impingement zone of hips with femoroacetabular
      impingement (and particularly those hips in the cleavage/thinning stage)
      expressed higher levels of certain inflammatory, anabolic, and catabolic genes,
      representing a heightened metabolic state. CLINICAL RELEVANCE: The articular
      cartilage from the impingement zone of hips with femoroacetabular impingement was
      metabolically hyperactive, supporting the concept that such impingement is a
      structural precursor to hip osteoarthritis.

PMID- 23965697
TI  - The direct and indirect costs to society of treatment for end-stage knee
      osteoarthritis.
AB  - BACKGROUND: Although total knee arthroplasty for end-stage osteoarthritis is a
      cost-effective procedure, payers are focusing on its indications and cost because
      of its high and growing use. Improvements in pain and physical function from
      total knee arthroplasty could yield benefits in the form of increased work life
      and lower disability payments. The purpose of this study was to estimate the
      value of total knee arthroplasty from a societal perspective, including the costs
      and benefits to patients, employers, and payers. METHODS: A Markov model was used
      to estimate the value of total knee arthroplasty for patients with end-stage
      osteoarthritis of the knee by comparing direct and indirect costs between
      surgical and nonsurgical treatment scenarios. Direct costs included all medical
      costs for surgical and nonsurgical treatment of osteoarthritis of the knee.
      Indirect costs were related to lost wages due to an inability to work, lower
      earnings, or receipt of disability payments. Direct and indirect costs and
      quality-of-life measures were incorporated into the Markov model to estimate the
      impact of total knee arthroplasty on costs over patients' lifetimes and quality
      adjusted life years. The assumptions used in the model were developed with use of
      claims and survey data as well as clinical expert opinion and the peer-reviewed
      literature. RESULTS: Compared with nonsurgical treatment, total knee arthroplasty
      increased lifetime direct costs by a mean of $20,635 (net present value in 2009
      U.S. dollars). These costs were offset by societal savings of $39,565 from
      reduced indirect costs, resulting in a lifetime societal net benefit from total
      knee arthroplasty of $18,930 per patient. Eighty-five percent of these savings
      originated from increased employment and earnings, with the remaining 15% from
      fewer missed workdays and lower disability payments. CONCLUSIONS: The estimated
      lifetime societal savings from the more than 600,000 total knee arthroplasties
      performed in the U.S. in 2009 were estimated to be approximately $12 billion.
      These societal savings primarily accrued to patients and employers. The study
      demonstrates the importance of a societal perspective when considering the costs
      and benefits of total knee arthroplasty and policies that will affect access to
      this procedure.

PMID- 23965698
TI  - Arthroscopic repair of massive contracted rotator cuff tears: aggressive release
      with anterior and posterior interval slides do not improve cuff healing and
      integrity.
AB  - BACKGROUND: Few studies of large-to-massive contracted rotator cuff tears have
      examined the arthroscopic complete repair obtained by a posterior interval slide
      and whether the clinical outcomes or structural integrity achieved are better
      than those after partial repair without the posterior interval slide. METHOD: The
      study included forty-one patients with large-to-massive contracted rotator cuff
      tears, not amenable to complete repair with margin convergence alone. The
      patients underwent either arthroscopic complete repair with a posterior interval
      slide and side-to-side repair of the interval slide edge (twenty-two patients;
      Group P) or partial repair with margin convergence (nineteen patients; Group M).
      The patient assignment was not randomized. The Simple Shoulder Test (SST),
      American Shoulder and Elbow Surgeons (ASES) score, University of California at
      Los Angeles (UCLA) shoulder score, and range of motion were used to compare the
      functional outcomes. Preoperative and six-month postoperative magnetic resonance
      arthrography (MRA) images were compared within or between groups. RESULTS: At the
      two-year follow-up evaluation, the SST, ASES score, UCLA score, and range of
      motion had significantly improved (p < 0.001 for all) in both groups. However, no
      significant differences were detected between groups. Even though the difference
      in preoperative tear size on MRA images was not significant, follow-up MRA images
      identified a retear in twenty patients (91%) in Group P and a significant
      difference in tear size between groups (p = 0.007). CONCLUSIONS: The complete
      repair group with an aggressive release had no better clinical or structural
      outcomes compared with the partial repair group with margin convergence alone for
      large-to-massive contracted rotator cuff tears. In addition, the complete repair
      group had a 91% retear rate and a greater defect on follow-up MRA images. Even
      though this study had a relatively short-term follow-up, a complete repair of
      large-to-massive contracted rotator cuff tears, with an aggressive release such
      as posterior interval slide, may not have an increased benefit compared with
      partial repair without posterior interval slide.

PMID- 23965699
TI  - Lengthening of the gastrocnemius-soleus complex: an anatomical and biomechanical
      study in human cadavers.
AB  - BACKGROUND: Lengthening of the gastrocnemius-soleus complex is frequently
      performed for equinus deformity. Many techniques have been described, but there
      is uncertainty regarding the precise details of some surgical procedures.
      METHODS: The surgical anatomy of the gastrocnemius-soleus complex was
      investigated, and standardized approaches were developed for the procedures
      described by Baumann, Strayer, Vulpius, Baker, Hoke, and White. The biomechanical
      characteristics of these six procedures were then compared in three randomized
      trials involving formaldehyde-preserved human cadaveric lower limbs. After one of
      the lengthening procedures was performed, a measured dorsiflexion force was
      applied across the metatarsal heads with use of a torque dynamometer. Lengthening
      of the gastrocnemius-soleus complex was measured directly, by measuring the gap
      between the ends of the fascia or tendon. RESULTS: The gastrocnemius-soleus
      musculotendinous unit was subdivided into three zones. In Zone 1, it was possible
      to lengthen the gastrocnemius-soleus complex in either a selective or a
      differential manner-i.e., to lengthen the gastrocnemius alone or to lengthen the
      gastrocnemius and soleus by different amounts. The procedures performed in this
      zone (Baumann and Strayer procedures) were very stable but were limited with
      regard to the amount of lengthening achieved. Zone-2 lengthenings of the
      conjoined gastrocnemius aponeurosis and soleus fascia (Vulpius and Baker
      procedures) were not selective but were stable and resulted in significantly
      greater lengthening than Zone-1 procedures (p < 0.001). In Zone 3 (Hoke and White
      procedures), lengthenings of the Achilles tendon were neither selective nor
      stable but resulted in significantly greater lengthening than Zone-1 or 2
      procedures (p < 0.001). CONCLUSIONS: Surgical procedures for the correction of
      equinus deformity by lengthening of the gastrocnemius-soleus complex vary in
      terms of selectivity, stability, and range of correction. Procedures for the
      correction of equinus deformity have different anatomical and biomechanical
      characteristics. Clinical trials are needed to determine whether these
      differences are of clinical importance. It may be appropriate for surgeons to
      select a procedure involving the zone best suited to the clinical needs of a
      specific patient.

PMID- 23965700
TI  - Spinal anesthesia: should everyone receive a urinary catheter?: a randomized,
      prospective study of patients undergoing total hip arthroplasty.
AB  - BACKGROUND: The objective of this randomized prospective study was to determine
      whether a urinary catheter is necessary for all patients undergoing total hip
      arthroplasty under spinal anesthesia. METHODS: Consecutive patients undergoing
      total hip arthroplasty under spinal anesthesia were randomized to treatment with
      or without insertion of an indwelling urinary catheter. All patients received
      spinal anesthesia with 15 to 30 mg of 0.5% bupivacaine. The catheter group was
      subjected to a standard postoperative protocol, with removal of the indwelling
      catheter within forty-eight hours postoperatively. The experimental group was
      monitored for urinary retention and, if necessary, had straight catheterization
      up to two times prior to the placement of an indwelling catheter. RESULTS: Two
      hundred patients were included in the study. There was no significant difference
      between the two groups in terms of the prevalence of urinary retention, the
      prevalence of urinary tract infection, or the length of stay. Nine patients in
      the no-catheter group and three patients in the catheter group (following removal
      of the catheter) required straight catheterization because of urinary retention.
      Three patients in the catheter group and no patient in the no-catheter group had
      development of urinary tract infection. CONCLUSIONS: Patients undergoing total
      hip arthroplasty under spinal anesthesia appear to be at low risk for urinary
      retention. Thus, a routine indwelling catheter is not required for such patients.

PMID- 23965701
TI  - Outcome of surgical reconstruction after traumatic total brachial plexus palsy.
AB  - BACKGROUND: Double free muscle transfer for the treatment of traumatic total
      brachial plexus injury provides useful prehensile function. We studied the
      outcome of this muscle transfer procedure, including the changes in disability
      and quality-of-life scores. METHODS: Thirty-six patients with traumatic total
      brachial plexus injury who underwent double free muscle transfer for
      reconstruction from 2002 to 2008 and had a minimum follow-up of twenty-four
      months after the second free muscle transfer were studied. All were evaluated
      preoperatively and postoperatively with use of the Disabilities of the Arm,
      Shoulder and Hand (DASH) and Short Form-36 (SF-36) questionnaires. A separate
      questionnaire was used to determine job status, pain, use of the reconstructed
      hand, and satisfaction with the procedure. RESULTS: The mean patient age was
      twenty-nine years (range, sixteen to forty-nine years), and the mean duration of
      follow-up was thirty-six months (range, twenty-four to seventy-nine months). The
      mean active range of motion was 23 degrees  (range, 0 degrees  to 80 degrees )
      for shoulder flexion, 31 degrees  (range, 0 degrees  to 90 degrees ) for shoulder
      abduction, -18 degrees  (range, -80 degrees  to 40 degrees ) for shoulder
      external rotation, 62 degrees  (range, 0 degrees  to 130 degrees ) for the
      shoulder rotation arc, 119 degrees  (range, 90 degrees  to 150 degrees ) for
      elbow flexion, and -33 degrees  (range, -60 degrees  to -20 degrees ) for elbow
      extension. The power of elbow flexion was M4 in twenty-five patients and M3 in
      eleven. Twenty-three patients had triceps nerve reconstruction; extension was M0
      in two of these patients, M1 in seven, M2 in ten, and M3 in four. Total active
      motion of the fingers was 46 degrees  (range, 0 degrees  to 98 degrees ), with a
      mean hook grip strength of 4 kg (range, 0 to 12 kg). Wilcoxon tests revealed
      significant improvements in the DASH score and the SF-36 physical functioning,
      role physical, and physical component summary scores. The majority of patients
      worked but had changed their type of work, used the reconstructed hand in
      activities of daily living that required both hands, and were satisfied with the
      procedure. CONCLUSIONS: Double free muscle transfer yielded satisfactory function
      and allowed use of the reconstructed hand in activities that required both hands.
      The improvement in the DASH score was greater than that in the SF-36 score.

PMID- 23965702
TI  - Tourniquet use did not adversely affect recovery after arthroscopic meniscectomy.

PMID- 23965703
TI  - Cemented and uncemented implants did not differ in pain outcomes when used for
      hemiarthroplasty.

PMID- 23965704
TI  - Rehabilitation plus early ACL reconstruction and rehabilitation plus delayed
      reconstruction were similar at 5 years.

PMID- 23965705
TI  - Complications of distal radial and scaphoid fracture treatment.

PMID- 23965706
TI  - What's new in limb lengthening and deformity correction.

PMID- 23965707
TI  - The role of medial comminution and calcar restoration in varus collapse of
      proximal humeral fractures treated with locking plates.
AB  - BACKGROUND: Proximal humeral fractures that are treated with locked plate
      constructs remain susceptible to collapse into a varus position. The objectives
      of the present study were to examine how medial comminution affects fracture
      stability and to determine the effect of calcar fixation on osteosynthesis
      stability. METHODS: Eleven matched pairs of cadaveric humeri were osteotomized to
      create standard three-part fractures involving the surgical neck and the greater
      tuberosity. Five matched pairs were randomly assigned to have the medial calcar
      region remain intact. Six matched pairs had removal of a 10-mm medially based
      wedge of bone to simulate medial comminution. All fractures were stabilized in a
      uniform fashion with a proximal humeral locking plate. The constructs were
      secured, and the superior portion of the humeral head was subjected to
      compressive loading to induce varus collapse. Load-to-failure and energy-to
      failure values along with stiffness and displacement at the time of failure were
      determined. RESULTS: Medial comminution decreased the mean load to failure by 48%
      (523 N) (p = 0.015) and the mean energy to failure by 44% (2009 Nmm) (p = 0.013).
      The use of calcar screw fixation increased the mean load to failure by 31% (219
      N) (p = 0.002) and the mean energy to failure by 44% (1279 Nmm) (p = 0.006).
      CONCLUSIONS: Medial comminution significantly decreased the stability of proximal
      humeral fracture fixation constructs. Calcar restoration with screw fixation
      significantly improved the stability of repaired fractures in cadaveric
      specimens. CLINICAL RELEVANCE: The data suggest that medial comminution is a
      predictor of poor stability of proximal humeral fractures and that stability may
      be improved through calcar restoration.

PMID- 23965708
TI  - Long-term clinical outcomes of war-related hip disarticulation and transpelvic
      amputation.
AB  - BACKGROUND: The Iran-Iraq war (1980 to 1988) was one of the longest wars of the
      twentieth century. Few studies are available in the current literature evaluating
      the long-term results of proximal lower-extremity war-related amputations. The
      purpose of the present cross-sectional study was to evaluate the current health
      related quality of life and clinical musculoskeletal function of Iranian veterans
      with hip or hemipelvic amputation. METHODS: Seventy-six patients from a cohort of
      eighty-four veterans with hip disarticulation and transpelvic amputation
      participated in this study. A Persian version of Medical Outcomes Study Short
      Form-36 (SF-36) was completed for all of the veterans. RESULTS: The average
      duration of follow-up was 26.6 +/- 3.7 years. The average age (and standard
      deviation) of the veterans was 44.1 +/- 7.0 years. The average scores for the
      physical and mental health dimensions of the SF-36 were 45.85 +/- 21.56 and 57.98
      +/- 25.19, respectively. These data indicate that the amputees were doing better
      in the mental domain than in the physical domain. Forty-five patients with a
      primary amputation (97.8%) and ten with a secondary amputation (33.3%) complained
      of pain in the amputation stump. CONCLUSIONS: Veterans with proximal lower
      extremity amputation will need life-long care. Supervision starts with stump
      management and the application of appropriate surgical techniques at the time of
      the injury and continues with periodic examination throughout life.

PMID- 23965709
TI  - Chronic symptomatic os subfibulare in children.
AB  - BACKGROUND: Some children have persistent pain and instability following
      inversion injuries of the ankle. Radiographs may reveal a small osseous fragment
      distal to the lateral malleolus, suggesting an avulsion injury of the anterior
      talofibular ligament and/or calcaneofibular ligament. The avulsion injury may
      involve an os subfibulare, causing ligamentous laxity and chronic pain resulting
      from nonunion. This situation must be differentiated from an asymptomatic os
      subfibulare, which is a normal anatomic variant in 1% of children. The purpose of
      this study was to evaluate the intraoperative findings and long-term outcomes of
      patients treated operatively for symptomatic avulsion injuries or a symptomatic
      os subfibulare. METHODS: Twenty-three patients presented with chronic ankle pain
      and instability, tenderness anterior and distal to the lateral malleolus, and
      imaging studies (magnetic resonance imaging and/or stress radiographs) suspicious
      for avulsion injury of the anterior talofibular ligament and/or calcaneofibular
      ligament. After unsuccessful nonoperative treatment, all patients underwent
      excision of the osseous fragments, anatomic reconstruction of the anterior
      talofibular ligament with use of drill holes through the lateral malleolus, and a
      modified Brostrom procedure. RESULTS: The mean age of the patients was 10.4 years
      (range, eight to thirteen years) at the time of injury and 13.6 years (range,
      eight to seventeen years) at the time of surgery, representing a mean delay in
      diagnosis and treatment of 3.2 years. At a mean follow-up of 4.5 years (range,
      2.1 to 13.2 years), the mean Foot and Ankle Outcome Score was 91.4 (range, 87 to
      98) out of 100, with all but one patient returning to the preinjury recreational
      level. Only one patient had a long-term complication. CONCLUSIONS: In children
      with chronic pain and instability associated with an os subfibulare, surgical
      excision of the os subfibulare combined with reconstruction of the anterior
      talofibular ligament and a modified Brostrom procedure was effective in restoring
      ankle stability, eliminating pain, and permitting return to the preinjury
      functional level.

PMID- 23965710
TI  - Tibial nailing with the knee semi-extended: review of techniques and indications:
      AAOS exhibit selection.

PMID- 23965711
TI  - Use of patient-reported outcome measures in foot and ankle research.
AB  - BACKGROUND: In the orthopaedic literature, there is a wide range of clinical
      outcome measurement tools that have been used in evaluating foot and ankle
      procedures, disorders, and outcomes, with no broadly accepted consensus as to
      which tools are preferred. The purpose of this study was to determine the
      frequency and distribution of the various outcome instruments used in the foot
      and ankle literature, and to identify trends for use of these instruments over
      time. METHODS: We conducted a systematic review of all original clinical articles
      reporting on foot and/or ankle topics in six orthopaedic journals over a ten-year
      period (2002 to 2011). All clinical patient-reported outcome rating instruments
      used in these articles were recorded, as were study date, study design, clinical
      topic, and level of evidence. RESULTS: A total of 878 clinical foot and ankle
      articles that used at least one patient-reported outcome measure were identified
      among 16,513 total articles published during the ten-year period. There were 139
      unique clinical outcome scales used, and the five most popular scales (as a
      percentage of foot/ankle outcome articles) were the American Orthopaedic Foot &
      Ankle Society (AOFAS) scales (55.9%), visual analog scale (VAS) for pain (22.9%),
      Short Form-36 (SF-36) Health Survey (13.7%), Foot Function Index (FFI) (5.5%),
      and American Academy of Orthopaedic Surgeons (AAOS) outcomes instruments (3.3%).
      The majority of articles described Level-IV studies (70.1%); only 9.4% reported
      Level-I studies. CONCLUSIONS: A considerable variety of outcome measurement tools
      are used in the foot and ankle clinical literature, with a small proportion used
      consistently. The AOFAS scales continue to be used at a high rate relative to
      other scales that have been validated. Data from the present study underscore the
      need for a paradigm shift toward the use of consistent, valid, and reliable
      outcome measures for studies of foot and ankle procedures and disorders. It is
      not clear which existing validated outcome instruments will emerge as widely used
      and clinically meaningful. CLINICAL RELEVANCE: These data support the need for a
      paradigm shift toward the consistent use of valid and reliable outcome measures
      for foot and ankle clinical research.

PMID- 23965712
TI  - Benefits and risks of secondary data: Commentary on an article by Susan M. Odum,
      PhDc, et al.: "A cost-utility analysis comparing the cost-effectiveness of
      simultaneous and staged bilateral total knee arthroplasty".

PMID- 23965713
TI  - In the eye of the beholder: Commentary on an article by Joshua D. Auerbach, MD,
      et al.: "Mitigating adverse event reporting bias in spine surgery".

PMID- 23965714
TI  - Inflammatory events in cartilage in early stages of femoroacetabular impingement:
      Commentary on an article by Shingo Hashimoto, MD, PhD, et al.: "Molecular
      characterization of articular cartilage from young adults with femoroacetabular
      impingement".

PMID- 23965715
TI  - [Severe hypertriglyceridemia].

PMID- 23965716
TI  - [Medical service for sports events].
AB  - The medical service for sports events is for physicians and other healthcare
      professionals a particular challenge, depending on type and size of the event.
      Planning criteria exist but only in general terms and are often inadequate, so
      the preparation should based principally on experience. In addition to a good
      cooperation with the other partners of the emergency medical services, specific
      accidents and clinical pictures, as well as legal implications have to observed. 

PMID- 23965717
TI  - [Inflammatory bowel disease].
AB  - Inflammatory bowel diseases (IBD) show an increase of prevalence in Switzerland.
      Industrialization and urbanisation correlate with an increase of incidence. IBD
      are the result of a continuum of interactions between genetic factors, the
      intestinal microbial flora, the immune system as well as environmental factors.
      Treatment for active Crohn's disease includes primarily systemically acting
      steroids for induction of remission, whereas azathioprine, methotrexate and TNF
      antibodies are used for maintenance of remission. Treatment for ulcerative
      colitis includes mostly systemic acting steroids for induction of remission and
      topically and systemically acting 5-ASA products and TNF antibodies for
      maintenance of remission. For mild active disease 5-ASA drugs are effective. 

PMID- 23965718
TI  - [Heart failure - up to date].
AB  - Heart failure is a common disorder associated with high morbidity and mortality
      as well as increasing socio-economic costs. General practitioners take care of
      most of the affected patients. Knowledge on pathophysiology and modern treatment
      concepts are decisive for rational decision making. Patient management focuses on
      longer survival and higher quality of life. Major goals include reductions in
      unnecessary hospital admissions as well as appropriate and timely involvement of
      heart failure specialists. 

PMID- 23965719
TI  - [Therapies in multiple sclerosis].
AB  - Although there is still no cure for Multiple Sclerosis (MS), effective strategies
      are available to modify the disease course, to treat relapses, to manage
      symptoms, to improve functions, and to provide emotional support. In combination,
      these treatments enhance the quality of life for people living with MS. 

PMID- 23965721
TI  - [Are manual therapies effective in acute lumbar pain?].

PMID- 23965722
TI  - [5 days of systemic steroids in COPD exacerbation are adequate].

PMID- 23965723
TI  - [Cardiovascular primary prevention with omega 3 fatty acids: no effect on
      mortality].

PMID- 23965725
TI  - [CME ultrasound diagnosis 53. Lower abdominal pain. Iliopsoas syndrome].

PMID- 23965728
TI  - Vitexin 6, a novel lignan, induces autophagy and apoptosis by activating the Jun
      N-terminal kinase pathway.
AB  - Previous studies have reported that vitexins induce cytotoxic effects. In the
      present study, we investigate a new native lignan vitexin 6 (VB6) in vitro to
      determine the molecular mechanism underlying its cytotoxicity. We screened and
      cultured several tumor cell lines and subsequently analyzed VB6 cytotoxicity
      against 14 different tumor cell lines using a 3-(4,5-dimethythiazol-2-yl)-2,5
      diphenyl tetrazolium bromide assay. The expression of proteins that regulate
      apoptosis and autophagy was determined using western blot analysis. VB6 showed an
      excellent cytotoxic effect against various cancer cell lines in vitro. It induced
      apoptosis and autophagy of cancer cells. VB6-induced apoptosis showed a time
      dependent and concentration-dependent relationship with cleaved poly (ADP-ribose)
      polymerase, cleaved caspase-3, Bax upregulation, and Bcl-2 downregulation. The
      levels of Beclin-1 and LC3-II, which are markers for cell autophagy, gradually
      increased after VB6 treatment. Jun N-terminal kinase (JNK) phosphorylation was
      increased after VB6 treatment, accompanied by upregulation of P-Bcl-2 and P-C-Jun
      expression. Cotreatment with a JNK inhibitor significantly decreased VB6-induced
      cell death and downregulated P-Bcl-2, and cleaved PARP and Beclin-1 expression.
      The new native lignan VB6 inhibits cancer cell proliferation by activating the
      JNK pathway. We believe that VB6 could be a valuable chemotherapeutic drug after
      further evaluation.

PMID- 23965729
TI  - Mumps postexposure prophylaxis with a third dose of measles-mumps-rubella
      vaccine, Orange County, New York, USA.
AB  - Although the measles-mumps-rubella (MMR) vaccine is not recommended for mumps
      postexposure prophylaxis (PEP), data on its effectiveness are limited. During the
      2009-2010 mumps outbreak in the northeastern United States, we assessed
      effectiveness of PEP with a third dose of MMR vaccine among contacts in Orthodox
      Jewish households who were given a third dose within 5 days of mumps onset in the
      household's index patient. We compared mumps attack rates between persons who
      received a third MMR dose during the first incubation period after onset in the
      index patient and 2-dose vaccinated persons who had not. Twenty-eight (11.7%) of
      239 eligible household members received a third MMR dose as PEP. Mumps attack
      rates were 0% among third-dose recipients versus 5.2% among 2-dose recipients
      without PEP (p=0.57). Although a third MMR dose administered as PEP did not have
      a significant effect, it may offer some benefits in specific outbreak contexts.

PMID- 23965731
TI  - Hepatitis E virus genotype 4, Nanjing, China, 2001-2011.
AB  - During 2001-2011, hepatitis E virus (HEV) was found in the blood of patients in
      Nanjing, China. All HEV-positive patients had virus genotype 4; subgenotype 4a
      was predominant. The effective population of HEV in Nanjing increased in ~1980
      and continued until ~2003 when it plateaued. 

PMID- 23965732
TI  - BCR CDR3 length distributions differ between blood and spleen and between old and
      young patients, and TCR distributions can be used to detect myelodysplastic
      syndrome.
AB  - Complementarity-determining region 3 (CDR3) is the most hyper-variable region in
      B cell receptor (BCR) and T cell receptor (TCR) genes, and the most critical
      structure in antigen recognition and thereby in determining the fates of
      developing and responding lymphocytes. There are millions of different TCR Vbeta
      chain or BCR heavy chain CDR3 sequences in human blood. Even now, when high
      throughput sequencing becomes widely used, CDR3 length distributions (also called
      spectratypes) are still a much quicker and cheaper method of assessing repertoire
      diversity. However, distribution complexity and the large amount of information
      per sample (e.g. 32 distributions of the TCRalpha chain, and 24 of TCRbeta) calls
      for the use of machine learning tools for full exploration. We have examined the
      ability of supervised machine learning, which uses computational models to find
      hidden patterns in predefined biological groups, to analyze CDR3 length
      distributions from various sources, and distinguish between experimental groups.
      We found that (a) splenic BCR CDR3 length distributions are characterized by low
      standard deviations and few local maxima, compared to peripheral blood
      distributions; (b) healthy elderly people's BCR CDR3 length distributions can be
      distinguished from those of the young; and (c) a machine learning model based on
      TCR CDR3 distribution features can detect myelodysplastic syndrome with
      approximately 93% accuracy. Overall, we demonstrate that using supervised machine
      learning methods can contribute to our understanding of lymphocyte repertoire
      diversity. 

PMID- 23965730
TI  - Mapping resilience pathways of Indigenous youth in five circumpolar communities.
AB  - This introduction to the Special Issue Indigenous Youth Resilience in the Arctic
      reviews relevant resilience theory and research, with particular attention to
      Arctic Indigenous youth. Current perspectives on resilience, as well as the role
      of social determinants, and community resilience processes in understanding
      resilience in Indigenous circumpolar settings are reviewed. The distinctive role
      for qualitative inquiry in understanding these frameworks is emphasized, as is
      the uniquely informative lens youth narratives can offer in understanding
      Indigenous, cultural, and community resilience processes during times of social
      transition. We then describe key shared cross-site methodological elements of the
      Circumpolar Indigenous Pathways to Adulthood study, including sampling, research
      design, procedures, and analytic strategies. The site-specific papers further
      elaborate on methods, focusing on those elements unique to each site, and
      describe in considerable detail locally salient stressors and culturally
      patterned resilience strategies operating in each community. The concluding paper
      considers these across sites, exploring continuities and discontinuities, and the
      influence of cross-national social policies. 

PMID- 23965733
TI  - Oral food challenge to wheat: a near-fatal anaphylaxis and review of 93 food
      challenges in children.
AB  - BACKGROUND: Wheat allergy is among the most common food allergy in children, but
      few publications are available assessing the risk of anaphylaxis due to wheat.
      METHODS: In this study, we report the case of near-fatal anaphylaxis to wheat in
      a patient undergoing an oral food challenge (OFC) after the ingestion of a low
      dose (256 mg) of wheat. Moreover, for the first time, we analyzed the risk of
      anaphylaxis during an OFC to wheat in 93 children, compared to other more
      commonly challenged foods such as milk, egg, peanuts, and soy in more than 1000
      patients. RESULTS: This study, which includes a large number of OFCs to wheat,
      shows that wheat is an independent risk factor that is associated with
      anaphylaxis requiring epinephrine administration (Odds Ratio [OR] = 2.4) and
      anaphylaxis requiring epinephrine administration to low dose antigen (OR = 8.02).
      Other risk factors for anaphylaxis, anaphylaxis requiring epinephrine
      administration, and anaphylaxis to low dose antigen was a history of a prior
      reaction not involving only the skin (OR = 1.8, 1.9 and 1.8 respectively). None
      of the clinical variables available prior to performing the OFC could predict
      which children among those undergoing OFCs to wheat would develop anaphylaxis or
      anaphylaxis for low dose antigen. CONCLUSION: This study shows that wheat is an
      independent risk factor that is associated with anaphylaxis requiring epinephrine
      administration and anaphylaxis requiring epinephrine administration to low dose
      antigen.

PMID- 23965735
TI  - China's NanoCentre turns ten.

PMID- 23965734
TI  - p16INK4a in cellular senescence.

PMID- 23965736
TI  - Toxic effect of chemotherapy dosing using actual body weight in obese versus
      normal-weight patients: a systematic review and meta-analysis.
AB  - BACKGROUND: Many oncologists reduce chemotherapy doses in obese patients due to
      fear of excess toxic effect from very large weight-based calculations. While
      recent guidelines advise against this practice, quantitative summarization of the
      supporting evidence is not available. MATERIALS AND METHODS: We systematically
      identified studies that compared toxic effect or survival outcomes between obese
      and normal-weight adults receiving chemotherapy dosed by actual body weight
      (ABW). We pooled odds ratios (OR) and 95% confidence intervals (CI) using random
      effects models. RESULTS: Of 5490 records screened, 12 studies representing 9314
      relevant patients met inclusion criteria. The large majority of reported toxic
      effect and survival outcomes did not statistically differ between obese and
      normal-weight subjects. Exceptions included five studies in which one or more
      toxic effect or survival outcomes statistically favored obese patients, and one
      study that statistically favored normal-weight patients. Pooling usable data,
      rates of toxic effects were similar or lower in obese patients (grade 3/4
      hematologic toxic effect: OR 0.73, CI 0.55-0.98, 4 studies; grade 3/4
      nonhematologic toxic effect: OR 0.98, CI 0.76-1.26, 3 subgroups; any grade 3/4
      toxic effect: OR 0.75, CI 0.65-0.87, three studies). CONCLUSIONS: Obese patients
      receiving chemotherapy based on ABW experience similar or lower rates of toxic
      effects compared with normal-weight patients, and survival outcomes do not
      differ.

PMID- 23965737
TI  - Theoretical study of water adsorption and dissociation on Ta3N5(100) surfaces.
AB  - Water adsorption and dissociation on the perfect, oxygen containing and nitrogen
      vacancy containing Ta3N5(100) surfaces are systematically studied by density
      functional theory calculations. The results show that the perfect Ta3N5(100)
      surface is very active for water dissociation because of the dangling bonds
      formed on the perfect Ta3N5(100) surface. The presence of oxygen on the surface
      is able to stabilize the Ta3N5(100) surface but not to facilitate water
      dissociation, which may be ascribed to the saturation of surface dangling bonds
      by oxygen. The presence of a nitrogen vacancy on the surface is able to
      facilitate water dissociation, but Ta3N5(100) surfaces with nitrogen vacancies
      are not stable. We found that keeping the impurity oxygen as less as possible is
      one effective approach to enhance the water splitting ability of Ta3N5. We
      propose that doping with foreign elements is one potential method to obtain a
      clean Ta3N5(100) surface, since the oxygen concentration may be adjusted by
      competition between oxygen and foreign elements. 

PMID- 23965738
TI  - The impact of a large-scale power outage on hemodialysis center operations.
AB  - INTRODUCTION: On June 29, 2012, mid-Atlantic storms resulted in a large-scale
      power outage affecting up to three million people across multiple (US) states.
      Hemodialysis centers are dependent on electricity to provide dialysis care to end
      stage renal disease patients. The objective of this study was to determine how
      the power outage impacted operations in a sample of hemodialysis centers in the
      impacted regions. METHODS: The sample consisted of all hemodialysis centers
      located in the District of Columbia and a total of five counties with the largest
      power losses in West Virginia, Virginia, and Maryland. A semi-structured
      interview guide was developed, and the charge nurse or supervisor in each
      facility was interviewed. The survey questions addressed whether their centers
      lost power, if so, for how long, where their patients received dialysis, whether
      their centers had backup generators, and if so, whether they had any problems
      operating them, and whether their center received patients from other centers if
      they had power. RESULTS: Calls were placed to 90 dialysis centers in the sampled
      areas and a 90% response rate was achieved. Overall, hemodialysis operations at
      approximately 30% (n = 24) of the centers queried were impacted by the power
      outage. Of the 36 centers that lost power, 31% (n = 11) referred their patients
      to other dialysis centers, 22% (n = 8) accommodated their patients during a later
      shift or on a different day; the rest of the centers either experienced brief
      power outages that did not affect operations or experienced a power outage on
      days that the center is usually closed. Some centers in the study cohort reported
      receiving patients from other centers for dialysis 33% (n = 27). Thirty-two
      percent (n = 26) of the centers queried had backup generators on site. Eleven
      percent (n = 4) of the centers experiencing power outages reported that backup
      generators were brought in by their parent companies. CONCLUSIONS: Comprehensive
      emergency planning for dialysis centers should include provisions for having
      backup generators on site, having plans in place for the timely delivery of a
      generator during a power outage, or having predesignated backup dialysis centers
      for patients to receive dialysis during emergencies. Most dialysis centers
      surveyed in this study were able to sustain continuity of care by implementing
      such pre-existing emergency plans.

PMID- 23965739
TI  - Memoir: curiosity rewarded!
AB  - EDITORS' INTRODUCTION: The following reminiscence by Lucy Balian Rorke-Adams is
      the eighth autobiography in a series published in the Journal of Neuropathology
      and Experimental Neurology. These have been solicited from senior members of the
      neuropathology community who have been noted leaders and contributors to
      neuroscience and to the American Association of Neuropathologists (AANP) and have
      a historical perspective of the importance of neuropathology in diagnosis,
      education, and research. It is hoped that this series will entertain, enlighten,
      and present members of the AANP with a better sense of the legacy that we have
      inherited, as well as reintroduce our respected neuroscientists as humans having
      interesting lives filled with joys and sorrows and allow them to present their
      lives in their own words.MNH, RAS.

PMID- 23965740
TI  - Genome-wide DNA copy number analysis of desmoplastic infantile astrocytomas and
      desmoplastic infantile gangliogliomas.
AB  - Little is known about the molecular features of desmoplastic infantile
      ganglioglioma (DIG) and desmoplastic infantile astrocytoma (DIA). We performed a
      genome-wide DNA copy number analysis in combination with a multiplex ligation
      dependent probe amplification-based analysis of copy number changes of candidate
      genes in 4 DIAs and 10 DIGs. Molecular inversion probe (MIP) assay showed that
      large chromosomal alterations were rare among DIG and DIA. Focal recurrent
      genomic losses were observed in chromosome regions such as 5q13.3, 21q22.11, and
      10q21.3 in both DIA and DIG. Principal component analysis did not show any
      significant differences between the molecular profiles of DIG and DIA, and a
      hierarchical cluster analysis did not clearly separate the 2 tumor groups
      according to their molecular profiles. In 6 cases, gain of genomic material at
      7q31 (corresponding to MET gene) was found in multiplex ligation-dependent probe
      amplification (MLPA) analysis. Furthermore, two cases showed gain at 4q12, and a
      single case showed BRAF mutation. In agreement with previous analyses, this study
      demonstrates the absence of consistent recurrent chromosomal alterations in DIA
      and DIG and overall rarity of the BRAF mutation in these tumors. Notably, these
      results suggest that DIA and DIG represent a histologic spectrum of the same
      tumor rather than 2 separate entities. 

PMID- 23965741
TI  - Molecular and clinical risk factors for recurrence of skull base chordomas: gain
      on chromosome 2p, expression of brachyury, and lack of irradiation negatively
      correlate with patient prognosis.
AB  - Chordomas are invasive tumors that develop from notochordal remnants and
      frequently occur in the skull base. The T gene and its product (brachyury) have
      recently been suggested to play an important role in chordoma progression. To
      date, few studies have investigated the relationship between the
      molecular/genetic characteristics of chordoma and patient prognosis. We analyzed
      37 skull base chordomas for chromosomal copy number aberrations using comparative
      genomic hybridization, brachyury expression by immunohistochemistry, and T gene
      copy number by fluorescence in situ hybridization. The results of these molecular
      analyses and clinical parameters were compared with the patients' clinical
      courses. Univariate analyses using the log-rank test demonstrated that losses on
      chromosome 1p and gains on 1q and 2p were negatively correlated with progression
      free survival, as were factors such as female sex, partial tumor removal, lack of
      postoperative irradiation, and high MIB-1 index. Expression of brachyury and copy
      number gain of the T gene were also significantly associated with shorter
      progression-free survival. Multivariate analysis using the Cox hazards model
      showed that lack of irradiation, gain on chromosome 2p, and expression of
      brachyury were independently associated with a poor prognosis. Our results
      suggest that brachyury-negative chordomas arebiologically distinct from brachyury
      positive chordomas and that T/brachyury might be an appropriate molecular
      therapeutic target for chordoma. 

PMID- 23965742
TI  - Cerebrospinal fluid tau cleaved by caspase-6 reflects brain levels and cognition
      in aging and Alzheimer disease.
AB  - Caspase-6 (Casp6) activation in the brain is implicated early in the pathogenesis
      of Alzheimer disease (AD). In view of the need for early AD diagnosis, brain
      Casp6 activity was investigated by measuring Tau cleaved by Casp6 (TauDeltaCasp6)
      protein in postmortem cerebrospinal fluid (CSF) of 7 non-cognitively impaired; 5
      mild cognitively impaired; and 12 mild, moderate, and severe AD patients. Levels
      of TauDeltaCasp6 in CSF accurately reflected the levels of active Casp6 and
      TauDeltaCasp6 detected using immunohistochemistry in hippocampal sections from
      the same individuals. Levels of CSF TauDeltaCasp6 significantly correlated with
      AD severity and with lower Global Cognitive Scores; Mini-Mental State Examination
      scores; and episodic, semantic, and working memory scores. Regression analyses
      suggested that the CSF TauDeltaCasp6 levels combined with TauDeltaCasp6 brain
      pathology predict cognitive performance. These results indicate that CSF
      TauDeltaCasp6 levels hold promise as a novel early biomarker of AD. 

PMID- 23965744
TI  - Disruption of CDH2/N-cadherin-based adherens junctions leads to apoptosis of
      ependymal cells and denudation of brain ventricular walls.
AB  - Disruption/denudation of the ependymal lining has been associated with the
      pathogenesis of various human CNS disorders, including hydrocephalus, spina
      bifida aperta, and periventricular heterotopia. It has been traditionally
      considered that ependymal denudation is a consequence of mechanical forces such
      as ventricular enlargement. New evidence indicates that ependymal disruption can
      precede ventricular dilation, but the cellular and molecular mechanisms involved
      in the onset of ependymal denudation are unknown. Here, we present a novel model
      to study ependymal cell pathophysiology and demonstrate that selective disruption
      of N-cadherin-based adherens junctions is sufficient to provoke progressive
      ependymal denudation. Blocking N-cadherin function using specific peptides that
      interfere with the histidine-alanine-valine extracellular homophilic interaction
      domain caused early pathologic changes characterized by disruption of zonula
      adherens and abnormal intracellular accumulation of N-cadherin. These changes
      then triggered massive apoptosis of ependymal cells and denudation of brain
      ventricular walls. Because no typical extrinsic mechanical factors such as
      elevated pressure or stretching forces are involved in this model, the critical
      role of N-cadherin-based adherens junctions in ependymal survival/physiology is
      highlighted. Furthermore, the results suggest that abnormal adherens junctions
      between ependymal cells should be considered as key components of the
      pathogenesis of CNS disorders associated with ependymal denudation. 

PMID- 23965743
TI  - Skeletal muscle biopsy analysis in reducing body myopathy and other FHL1-related
      disorders.
AB  - FHL1 mutations have been associated with various disorders that include reducing
      body myopathy (RBM), Emery-Dreifuss-like muscular dystrophy, isolated
      hypertrophic cardiomyopathy, and some overlapping conditions. We report a
      detailed histochemical, immunohistochemical, electron microscopic, and
      immunoelectron microscopic analyses of muscle biopsies from 18 patients carrying
      mutations in FHL1: 14 RBM patients (Group 1), 3 Emery-Dreifuss muscular dystrophy
      patients (Group 2), and 1 patient with hypertrophic cardiomyopathy and muscular
      hypertrophy (Group 2). Group 1 muscle biopsies consistently showed RBs associated
      with cytoplasmic bodies. The RBs showed prominent FHL1 immunoreactivity whereas
      desmin, alphaB-crystallin, and myotilin immunoreactivity surrounded RBs. By
      electron microscopy, RBs were composed of electron-dense tubulofilamentous
      material that seemed to spread progressively between the myofibrils and around
      myonuclei. By immunoelectron microscopy, FHL1 protein was found exclusively
      inside RBs. Group 2 biopsies showed mild dystrophic abnormalities without RBs;
      only minor nonspecific myofibrillar abnormalities were observed under electron
      microscopy. Molecular analysis revealed missense mutations in the second FHL1 LIM
      domain in Group 1 patients and ins/del or missense mutations within the fourth
      FHL1 LIM domain in Group 2 patients. Our findings expand the morphologic features
      of RBM, clearly demonstrate the localization of FHL1 in RBs, and further
      illustrate major morphologic differences among different FHL1-related myopathies.

PMID- 23965745
TI  - Intact numbers of cerebellar purkinje and granule cells in sudden infant death
      syndrome: a stereologic analysis and critical review of neuropathologic evidence.
AB  - Despite much research during recent decades, the etiology and pathogenesis of
      sudden infant death syndrome (SIDS) remain unknown. Because of the role of the
      cerebellum in respiratory and cardiovascular control, it has been proposed that
      it plays an important role in the pathogenesis of SIDS. To date, 5 postmortem
      studies on the cerebellum of SIDS cases have yielded conflicting results. Using a
      rigorous design-based stereologic approach, we investigated postmortem cerebella
      from 9 SIDS patients who died between 2 and 10 months of age and from 9 age- and
      sex-matched control children. Neither the volumes of the cerebellar external
      granule cell layer, molecular layer, internal granule cell layer (including the
      Purkinje cell layer), and white matter nor the total numbers of Purkinje cells,
      granule cells in the internal granule cell layer, and the number of granule cells
      per Purkinje cell showed statistically significant differences between the SIDS
      cases and the controls. Based on these observations, we conclude that structural
      alterations in cerebellar development are not involved in the etiology and
      pathogenesis of SIDS. 

PMID- 23965746
TI  - Sulfonylurea receptor 1 expression in human cerebral infarcts.
AB  - In animal models of stroke, sulfonylurea receptor 1 (Sur1), a member of the
      adenosine triphosphate binding cassette transporter gene family, is
      transcriptionally upregulated in neural and vascular cells in which it plays a
      leading role in edema formation and necrotic cell death. To date, expression of
      Sur1 in the brains of humans with cerebral infarcts has not been systematically
      evaluated. We examined Sur1 expression in postmortem specimens obtained from 13
      patients within the first 31 days after focal infarcts, 5 patients with lacunar
      infarcts, and 6 normal control brains using immunohistochemistry. Elevated
      immunoreactivity for Sur1 was detected in all cases of focal infarcts, with 3
      distinct temporal patterns of expression: 1) neurons and endothelium showed the
      greatest elevation during the first week, after which levels declined; 2)
      astrocytes and microglia/macrophages showed progressive increases during the
      first 31 days; and 3) neutrophils near the infarct showed prominent
      immunoreactivity that did not change over time. Upregulation of Sur1 was
      corroborated using in situ hybridization for Abcc8 mRNA. Sulfonylurea receptor 1
      immunoreactivity in lacunar infarcts was less prominent and more sporadic than in
      nonlacunar infarcts. In conjunction with previous studies, these data suggest
      that Sur1 may be a promising treatment target in patients with acute cerebral
      infarction. 

PMID- 23965747
TI  - Interaction between akt1-positive neurons and age at surgery is associated with
      surgical outcome in children with isolated focal cortical dysplasia.
AB  - To identify pathologic characteristics that are associated with outcome, we
      performed a retrospective analysis of the clinical, radiologic, and pathologic
      features of 44 children with isolated focal cortical dysplasia (FCD) after
      epilepsy surgery. Based on the International League Against Epilepsy
      Classification, 16 patients had FCD Type I and 28 subjects had FCD Type II. A
      significantly higher percentage of subjects with FCD Type IIb versus Types I and
      IIa were seizure-free after surgery. Akt (also known as protein kinase B) is the
      main downstream target of phosphatidylinositol 3'-kinase and has been implicated
      in epilepsy pathogenesis. Semiquantitative analysis of cortical gliosis and
      quantitation of Akt1-immunoreactive neurons indicated that individuals with FCD
      Type II were more likely to have diffuse astrogliosis and higher counts of Akt1
      positive neurons versus those with FCD Type I. A logistic regression model,
      including Akt1-positive neurons, age at surgery, and the interaction of these
      factors, was significantly associated with seizure-free outcome. This study
      provides evidence that astrogliosis and overexpression of neuronal Akt1 protein
      may be important factors in the pathogenesis of FCD and suggests that the
      pathogenesis of FCD Type I may differ from that of FCD Type II in children. 

PMID- 23965748
TI  - Involvement of histaminergic system in the anxiolytic-like activities of Morus
      alba leaves in mice.
AB  - The aim of this study was to identify the effects of 85% methanolic extract of
      Morus alba leaves (EMA), which is a traditional herb, in mice. The effects of EMA
      on the anxiolytic-like behaviour were studied using the elevated plus maze (EPM)
      and hole-board test. To elucidate the mode of action of the anxiolytic-like
      effects of EMA, the mice were subjected to the co-administration of EMA (200
      mg/kg, per os (p.o.)) and either antagonist. EMA (at 200 or 400 mg/kg)
      significantly increased the percentages of time-spent in the open arms and
      entries into the open arms of the EPM versus vehicle-treated control group
      (p<0.05). Moreover, in the hole-board test, EMA (200 and 400 mg/kg) significantly
      increased the number of head-dips versus vehicle-treated control group (p<0.05).
      However, there were no changes in the locomotor activity and myorelaxant effects
      in any group compared with the vehicle-treated control group. In addition, the
      anxiolytic-like effects of EMA were abolished by thioperamide (10 mg/kg,
      intraperitoneally (i.p.)), which is a histamine H3 receptor antagonist. Moreover,
      results from reverse transcription polymerase chain reaction (RT-PCR) also
      revealed that the amygdalal histidine decarboxylase mRNA expression levels in EMA
      (200 mg/kg)-treated group were significantly higher than those in the vehicle
      treated controls (p<0.05). These results suggest that EMA might prove to be an
      effective anxiolytic agent and that EMA acts via the histaminergic system in
      central nerve system. 

PMID- 23965750
TI  - Financial impact of surgical site infections on hospitals: the hospital
      management perspective.
AB  - IMPORTANCE: Surgical site infections (SSIs) may increase health care costs, but
      few studies have conducted an analysis from the perspective of hospital
      administrators. OBJECTIVE: To determine the change in hospital profit due to
      SSIs. DESIGN: Retrospective study of data from January 1, 2007, to December 31,
      2010. SETTING: The study was performed at 4 of The Johns Hopkins Health System
      acute care hospitals in Maryland: Johns Hopkins Bayview (560 beds); Howard County
      General Hospital (238 beds); The Johns Hopkins Hospital (946 beds); and Suburban
      Hospital (229 beds). PARTICIPANTS: Eligible patients for the study included those
      patients admitted to the 4 hospitals between January 1, 2007, and December 31,
      2010, with complete data and the correct International Classification of
      Diseases, Ninth Revision code, as determined by the infection preventionist.
      Infection preventionists performed complete medical record review using National
      Healthcare Safety Network definitions to identify SSIs. Patients were stratified
      using the All Patient Refined Diagnosis Related Groups to estimate the change in
      hospital profit due to SSIs. EXPOSURE: Surgical site infections. MAIN OUTCOMES
      AND MEASURES: The outcomes of the study were the difference in daily total
      charges, length of stay (LOS), 30-day readmission rate, and profit for patients
      with an SSI when compared with patients without an SSI. The hypothesis,
      formulated prior to data collection, that patients with an SSI have higher daily
      total costs, a longer LOS, and higher 30-day readmission rates than patients
      without an SSI, was tested using a nonpaired Mann-Whitney U test, an analysis of
      covariance, and a Pearson chi2 test. Hospital charges were used as a proxy for
      hospital cost. RESULTS The daily total charges, mean LOS, and 30-day readmission
      rate for patients with an SSI compared with patients without an SSI were $7493 vs
      $7924 (P = .99); 10.56 days vs 5.64 days (P < .001); and 51.94 vs 8.19
      readmissions per 100 procedures (P < .001). The change in profit due SSIs was $2
      268 589. CONCLUSIONS AND RELEVANCE: The data suggest that hospitals have a
      financial incentive to reduce SSIs, but hospitals should expect to see an
      increase in both cost and revenue when SSIs are reduced.

PMID- 23965749
TI  - Salidroside inhibits endogenous hydrogen peroxide induced cytotoxicity of
      endothelial cells.
AB  - Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L., shows
      potent antioxidant property. Herein, we investigated the protective effects of
      salidroside against hydrogen peroxide (H2O2)-induced oxidative damage in human
      endothelial cells (EVC-304). EVC-304 cells were incubated in the presence or
      absence of low steady states of H2O2 (3-4 uM) generated by glucose oxidase (GOX)
      with or without salidroside. 3(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione
      (GSH) assays were performed, together with Hoechst 33258 staining and flow
      cytometric analysis using Annexin-V and propidium iodide (PI) label. The results
      indicated that salidroside pretreatment attenuated endogenous H2O2 induced
      apoptotic cell death in EVC-304 cells in a dose-dependent pattern. Furthermore,
      Western blot data revealed that salidroside inhibited activation of caspase-3, 9
      and cleavage of poly(ADP-ribose) polymerase (PARP) induced by endogenous H2O2. It
      also decreased the expression of Bax and rescued the balance of pro- and anti
      apoptotic proteins. All these results demonstrated that salidroside may present a
      potential therapy for oxidative stress in cardiovascular and cerebrovascular
      diseases. 

PMID- 23965751
TI  - Repeated transsphenoidal surgery or gamma knife radiosurgery in recurrent cushing
      disease after transsphenoidal surgery.
AB  - BACKGROUND: This study compared Gamma knife radiosurgery (GKRS) and repeated
      transsphenoidal adenomectomy (TSA) to find the best approach for recurrence of
      Cushing disease (CD) after unsuccessful first TSA. MATERIAL AND METHODS: Fifty
      two patients with relapse of CD after TSA were enrolled and randomly underwent a
      second surgery or GKRS as the next therapeutic approach. They were followed for a
      mean period of 3.05 +/- 0.8 years by physical examination and hormone measurement
      as well as magnetic resonance imaging. RESULTS: No significant difference was
      observed in sex ratio, mean age, adenoma type, follow-up duration, and initial
      hormone level between the two groups. No significant relationship was found
      between preoperative 24-hour free urine cortisol and disease-free months or tumor
      volume among both groups. Our statistical analysis showed higher recurrence-free
      interval in the GKRS group compared with TSA group. CONCLUSION: With longer
      recurrence-free interval, GKRS could be considered a good treatment alternative
      to repeated TSA in recurrent CD.

PMID- 23965752
TI  - Reductive assembly of cyclobutadienyl and diphosphacyclobutadienyl rings at
      uranium.
AB  - Despite the abundance of f-block-cyclopentadienyl, arene, cycloheptatrienyl and
      cyclo-octatetraenide complexes, cyclobutadienyl derivatives are unknown in spite
      of their prevalence in the d-block. Here we report that reductive [2+2]
      cycloaddition reactions of diphenylacetylene and (2,2
      dimethylpropylidyne)phosphine with uranium(V)-inverted sandwich 10pi-toluene
      tetra-anion complexes results in the isolation of inverted sandwich
      cyclobutadienyl and diphosphacyclobutadienyl dianion uranium(IV) complexes.
      Computational analysis suggests that the bonding is predominantly electrostatic.
      Although the psi4 molecular orbital in the cyclobutadienyl and
      diphosphacyclobutadienyl ligands exhibits the correct symmetry for delta-bonding
      to uranium, the dominant covalent contributions arise from pi-bonding involving
      psi2 and psi3 orbital combinations. This contrasts with uranium complexes of
      larger arenes and cyclo-octatetraenide, where delta-bonding dominates. This
      suggests that the angular requirements for uranium to bond to a small four
      membered ring favours pi-bonding, utilizing 5f- instead of 6d-orbitals, over
      delta-bonding that is favoured with larger ligands, where 6d-orbitals can become
      involved in the bonding. 

PMID- 23965753
TI  - Functions and Positions of Corporate Occupational Health Managers in Company-Wide
      Occupational Health Management.
AB  - Objectives: It has become necessary for Japanese corporations to manage
      occupational health (OH) programs consistently throughout their organizations.
      Corporations need to clarify their health policies, develop standardized
      programs, assign OH staff, and ensure that they communicate with each other. To
      realize such conditions, many occupational physicians (OPs), who have the skills
      to lead corporation-wide OH activities, are now being assigned to head offices of
      corporations and referred to as corporate OH managers. However, there has been no
      research to date in Japan on their actual situation and function. We conducted an
      interview study of corporate OH managers to clarify their functions and positions
      in corporations. Subjects and Methods: We conducted semi-structural interviews
      with 14 corporate OH managers in large corporations employing more than 5,000
      workers and multiple OPs. Interview scripts were coded to identify their
      functions as corporate OH managers and the context of their positions within
      corporate-wide OH management systems. Results: Five contexts were suggested. 1)
      Corporate OH managers played central roles in developing corporate health
      policies, standards and plans. 2) Head office department managers who supervised
      the sites distributed the policies and standards, and corporate OH managers
      instructed site OPs and OH staff. 3) In some corporations, corporate OH managers
      participated in the evaluation process of OH programs as part of occupational
      safety and health management systems or business audits. 4) Corporate OH managers
      led communications among OPs and OH staff by facilitating corporate OH meetings,
      and provided technical training. 5) Corporate OH managers in positions that
      enabled them to report directly or indirectly to decision makers (i.e., directors
      in charge) on human resource issues. Discussion: The results of this study
      suggest that companies that promote consistent company-wide OH programs also
      utilized the professional knowledge of OH managers as well as their decision
      making skills and direction processes. They also suggest that these companies
      play significant roles in securing qualified OH professionals and reaching a
      common understanding of corporate OH systems. It is necessary to study cases of
      corporate OH managers to clarify their essential competences and to develop
      appropriate training programs.

PMID- 23965754
TI  - Estimation of Organic Vapor Breakthrough Time of Activated Carbon Bed Using NIOSH
      MultiVaporTM Software.

PMID- 23965755
TI  - Loss of PDCD4 contributes to enhanced chemoresistance in Glioblastoma multiforme
      through de-repression of Bcl-xL translation.
AB  - Glioblastoma multiforme (GBM) is the most common and aggressive form of tumor of
      the central nervous system. Despite significant efforts to improve treatments,
      patient survival rarely exceeds 18 months largely due to the highly
      chemoresistant nature of these tumors. Importantly, misregulation of the
      apoptotic machinery plays a key role in the development of drug resistance. We
      previously demonstrated that Bcl-xL, an important anti-apoptotic protein, is
      regulated at the level of translation by the tumor suppressor programmed cell
      death 4 (PDCD4). We report here a strong correlation between low expression of
      PDCD4 and high expression of Bcl-xL in adult de novo GBM, GBM tumor initiating
      cells, and established GBM cell lines. Importantly, high Bcl-xL expression
      correlated significantly with poor progression and patient survival. We
      demonstrate that re-expression of PDCD4 in GBM cells down-regulated Bcl-xL
      expression and decreased cell viability. Finally, we show that direct inhibition
      of Bcl-xL by small molecule antagonist ABT-737 sensitizes GBM cells to
      doxorubicin. Our results identify Bcl-xL as a novel marker of GBM chemoresistance
      and advocate for the combined use of Bcl-xL antagonists and existing
      chemotherapeutics as a treatment option for this aggressive tumor. 

PMID- 23965756
TI  - Continued evolution of West Nile virus, Houston, Texas, USA, 2002-2012.
AB  - We investigated the genetics and evolution of West Nile virus (WNV) since initial
      detection in the United States in 1999 on the basis of continual surveillance
      studies in the Houston, Texas, USA, metropolitan area (Harris County) as a
      surrogate model for WNV evolution on a national scale. Full-length genomic
      sequencing of 14 novel 2010-2012 WNV isolates collected from resident birds in
      Harris County demonstrates emergence of 4 independent genetic groups distinct
      from historical strains circulating in the greater Houston region since 2002.
      Phylogenetic and geospatial analyses of the 2012 WNV isolates indicate closer
      genetic relationship with 2003-2006 Harris County isolates than more recent 2007
      2011 isolates. Inferred monophyletic relationships of these groups with several
      2006-2009 northeastern US isolates supports potential introduction of a novel WNV
      strain in Texas since 2010. These results emphasize the need to maintain WNV
      surveillance activities to better understand WNV transmission dynamics in the
      United States. 

PMID- 23965757
TI  - Outbreak of chikungunya virus infection, Vanimo, Papua New Guinea.
AB  - In June 2012, health authorities in Papua New Guinea detected an increase in
      febrile illnesses in Vanimo. Chikungunya virus of the Eastern/Central/Southern
      African genotype harboring the E1:A226V mutation was identified. This ongoing
      outbreak has spread to >=8 other provinces and has had a harmful effect on public
      health. 

PMID- 23965758
TI  - How can flexibility be integrated into coexistence regulations? A review.
AB  - Member states in the European Union (EU) implemented both ex ante coexistence
      regulations and ex post liability schemes to ensure that genetically modified
      (GM) and non-GM crops can be cultivated side by side without excluding any
      agricultural option. Although proportionate coexistence is best achieved if
      regulated in a flexible manner, most implemented coexistence regulations merely
      rely on rigid measures. Flexible coexistence regulations, however, would reduce
      the regulatory burden on certain agricultural options and avoid jeopardizing
      economic incentives for coexistence. Flexibility can be integrated at: (i) the
      regulatory level by relaxing the rigidity of coexistence measures in ex ante
      regulations, yet without offsetting incentives to implement coexistence measures;
      (ii) the farm level by recommending the use of pollen barriers instead of large
      and fixed isolation distances; and (iii) the national/regional level by allowing
      diversified coexistence measures, which are adapted to the heterogeneity of
      farming in the EU. Owing to difficulties of implementation, the adoption of
      flexible and proportionate coexistence regulations will inevitably entail
      challenges.

PMID- 23965759
TI  - A synthesis of gamma-trifluoromethyl alpha,beta-unsaturated gamma-butyrolactones
      using CF(3)SiMe(3) as a trifluoromethylating agent.
AB  - A general synthesis of gamma-trifluoromethyl alpha,beta-unsaturated gamma
      butyrolactones is described. The fluoride-catalyzed nucleophilic addition of a
      trifluoromethyl (CF3) group generated from (trifluoromethyl)trimethylsilane
      (CF3SiMe3, Ruppert-Prakash reagent) to a masked maleic anhydride 1
      (cyclopentadiene-maleic anhydride adduct) provides the corresponding adducts 2
      with high stereoselectivity. The gamma-trifluoromethyl alpha,beta-unsaturated
      gamma-butyrolactones 4 were obtained after treatment of the adducts 2 with
      Grignard reagents, followed by flash-vacuum pyrolysis. 

PMID- 23965760
TI  - Temperature response of the neuronal cytoskeleton mapped via atomic force and
      fluorescence microscopy.
AB  - Neuronal cells change their growth properties in response to external physical
      stimuli such as variations in external temperature, stiffness of the growth
      substrate, or topographical guidance cues. Detailed knowledge of the mechanisms
      that control these biomechanical responses is necessary for understanding the
      basic principles that underlie neuronal growth and regeneration. Here, we present
      elasticity maps of living cortical neurons (embryonic rat) as a function of
      temperature, and correlate these maps to the locations of internal structural
      components of the cytoskeleton. Neurons display a significant increase in the
      average elastic modulus upon a decrease in ambient temperature from 37 to 25 
      degrees C. We demonstrate that the dominant mechanism by which the elasticity of
      the neurons changes in response to temperature is the stiffening of the actin
      components of the cytoskeleton induced by myosin II. We also report a reversible
      shift in the location and composition of the high-stiffness areas of the neuron
      cytoskeleton with temperature. At 37  degrees C the areas of the cell displaying
      high elastic modulus overlap with the tubulin-dense regions, while at 25  degrees
      C these high-stiffness areas correspond to the actin-dense regions of the
      cytoskeleton. These results demonstrate the importance of considering temperature
      effects when investigating cytoskeletal dynamics in cells. 

PMID- 23965761
TI  - Use of food label information by urban consumers in India - a study among
      supermarket shoppers.
AB  - OBJECTIVE: To study consumer knowledge and use of food labels. DESIGN: A cross
      sectional study employing both quantitative and qualitative methods. Intercept
      interviews were conducted with 1832 consumers at supermarket sites selected using
      a stratified random sampling procedure. This information was triangulated with
      twenty-one focus group discussions. SETTING: New Delhi and Hyderabad, two metro
      cities from north and south India. SUBJECTS: Adolescent (10-19 years), adult (20
      59 years) and elderly (>=60 years) consumers. RESULTS: While the national urban
      literacy rate is 84 %, about 99 % of the study participants were educated. About
      45 % reported that they buy pre-packaged foods once weekly and about a fifth buy
      them every day. Taste, quality, convenience and ease of use are the main reasons
      for buying pre-packaged foods. Although 90 % of consumers across the age groups
      read food labels, the majority (81 %) looked only for the manufacturing date or
      expiry/best before date. Of those who read labels, only a third checked nutrition
      information and ingredients. Nutrient information on labels was not often read
      because most consumers either lacked nutrition knowledge or found the information
      too technical to understand. About 60 % read quality symbols. A positive
      association was found between education level and checking various aspects of
      food labels. Women and girls concerned about 'fat' and 'sugar' intake read the
      nutrition facts panel. CONCLUSIONS: The intention of promoting healthy food
      choices through use of food labels is not being completely met. Since a majority
      of people found it difficult to comprehend nutrition information, there is a need
      to take up educational activities and/or introduce new forms of labelling.

PMID- 23965762
TI  - Effects of cholesterol on membrane molecular dynamics studied by fast field
      cycling NMR relaxometry.
AB  - Biological membranes are complex structures composed of various lipids and
      proteins. Different membrane compositions affect viscoelastic and hydrodynamic
      properties of membranes, which are critical to their functions. Lipid bilayer
      vesicles inserted by cholesterol not only enhance membrane surface motional
      behavior but also strengthen vesicle stability. Cholesterol-rich vesicles are
      similar to cell membranes in structure and composition. Therefore, cholesterol
      rich vesicles can represent a typical model for studying membrane dynamics and
      functions. In this study, nuclear magnetic relaxation dispersion was used to
      investigate the detailed molecular dynamics of membrane differences between
      vesicles and cholesterol vesicles in the temperature range of 278-298 K. Vesicles
      of two different sizes were prepared. The effect of cholesterol mainly affected
      the order fluctuation of membranes and the diffusional motion of lipid molecules.
      In addition, phase variations were also observed in liposomes that contained
      cholesterol from analyses of the distances between lipid molecules. 

PMID- 23965763
TI  - Prevalence of circumcision among men and boys aged 14 to 59 years in the United
      States, National Health and Nutrition Examination Surveys 2005-2010.
AB  - BACKGROUND: In 2009, an estimated 3590 new heterosexually acquired HIV infections
      occurred in males in the United States. Three randomized controlled trials
      demonstrated that male circumcision decreased a man's risk for HIV acquisition
      through heterosexual sex. We describe circumcision prevalence in US males and
      determine circumcision prevalence among males potentially at increased risk for
      heterosexually acquired HIV infection. METHODS: We estimated circumcision
      prevalence among men and boys aged 14 to 59 years using data from the National
      Health and Nutrition Examination Surveys 2005-2010. We defined men and boys with
      2 or more female partners in the last year as potentially at increased risk for
      heterosexually acquired HIV infection. RESULTS: Estimated circumcision prevalence
      was 80.5%. Prevalence varied significantly by year of birth, race/ethnicity,
      health insurance type, and family income. Circumcision prevalence among men and
      boys reporting 2 or more female partners in the last year was 80.4%, which
      corresponded to an estimated 3.5 million uncircumcised men and boys potentially
      at increased risk for heterosexually acquired HIV infection. Of these men and
      boys, 48.3% lacked health insurance. CONCLUSIONS: Circumcision prevalence in the
      United States differs by demographic group, and half of uncircumcised men and
      boys potentially at increased risk for heterosexually acquired HIV are uninsured.
      These data could inform recommendations and cost analyses concerning circumcision
      in the United States.

PMID- 23965764
TI  - Newborn circumcision: ensuring universal access.

PMID- 23965765
TI  - Evaluating the Internet as a sexually transmitted disease risk environment for
      teens: findings from the communication, health, and teens study.
AB  - BACKGROUND: Few studies have examined the association between sexual health risks
      and online sex-seeking among teenagers. The purpose of this study was to assess
      the associations between meeting sex partners online and a range of sexual risk
      behaviors and outcomes among adolescents. METHODS: Participants aged 13 to 19
      years were recruited from a publicly funded teen clinic in Florida. After
      obtaining informed consent/assent, 273 participants completed an audio computer
      assisted self-interview that included questions on demographics, sexual behavior,
      sexually transmitted disease (STD) history, and online sex-seeking behaviors and
      experiences. Participants also provided urine samples for chlamydia and gonorrhea
      testing. Data were analyzed using logistic regression to identify the association
      between having an online sex partner and sexual behaviors/outcomes. RESULTS:
      After adjusting for significant bivariate correlates, teens reporting online sex
      partners were more likely to be male, be multiracial, have a history of same-sex
      sexual activity, report a higher number of vaginal sex partners, and report a
      lower age at first vaginal sex. However, teens with online sex partners were no
      more likely to have ever had an STD or a current biological STD. CONCLUSIONS:
      This study is one of the first to correlate biological STD results to online
      sexual partnering data in a youth population. Although meeting a sex partner
      online was not associated with past or current STDs, it was associated with other
      sexual risk behaviors. Future research is needed to examine the complex nature of
      online sexual partnering among adolescents and to develop intervention
      approaches.

PMID- 23965766
TI  - Incidence of genital warts in adolescents and young adults in an integrated
      health care delivery system in the United States before human papillomavirus
      vaccine recommendations.
AB  - BACKGROUND: Information on genital wart incidence in adolescents and young adults
      before human papillomavirus (HPV) vaccination is important for understanding the
      impact of the vaccine on the epidemiology of this early outcome of HPV infection.
      METHODS: The study population included 11- to 29-year-old enrollees of Northern
      California Kaiser Permanente between July 1, 2000, and July 1, 2005, before the
      availability of the HPV vaccine. We identified genital warts with an algorithm
      combining genital wart-specific International Classification of Diseases, Ninth
      Revision, Clinical Modification codes (078.10, 078.11, and 078.19) with physician
      recorded anatomic locations. We calculated sex- and age-specific incidence rates
      of genital warts and described the specific anatomic location of presentation, as
      well as recurrences of genital warts. RESULTS: We identified 1,682 cases of
      genital warts among 181,264 individuals. The incidence rate was highest among
      women (6.3/1000 person-years) and men (2.9/1000 person-years) aged 20 to 24 years
      old. Among women (n = 96,792), 63.4% of the 1240 incident genital wart cases
      occurred on the vulva and 21.1% on the cervix. Among men (n = 84,472), 91.6% of
      the 442 incident genital wart cases did not have a specific anatomic location
      recorded. Most people with an incident genital wart diagnosis (87.2%) did not
      have a recurrence during the observation period. CONCLUSIONS: Our study found
      that the incidence of genital warts was highest among persons aged 20 to 24 years
      using a unique method to identify the location of the wart. Information on
      incidence of genital warts before vaccine use provides baseline data that can be
      used to measure HPV vaccine impact.

PMID- 23965767
TI  - Retreatment rates for uncomplicated gonorrhea infection: comparing ceftriaxone
      and azithromycin versus ceftriaxone and doxycycline.
AB  - BACKGROUND: The current recommended first-line regimen to treat gonorrhea is
      ceftriaxone in combination with either azithromycin or doxycycline. Azithromycin
      is the preferred second agent. We retrospectively measured and compared gonorrhea
      retreatment rates between patients receiving ceftriaxone plus azithromycin and
      those receiving ceftriaxone plus doxycycline. METHODS: Using data from public
      sexually transmitted disease clinics for patients treated for gonorrhea in
      Baltimore, Maryland, between January 2004 and December 2011, we measured time to
      retreatment from the date the ceftriaxone regimen was received. Censoring
      occurred on the earlier of 2 years posttreatment or March 31, 2012. Survival
      analysis methods were used to compare retreatment rates. RESULTS: One tenth
      (9.9%; n = 4457) of patients were retreated within 2 years. Treatment regimen was
      not related to time to retreatment (adjusted hazard ratio [aHR], 0.88; 95%
      confidence interval, 0.69-1.12). Patients receiving expedited partner therapy
      (EPT) were 45% less likely to be retreated (aHR, 0.55 [0.31-0.96]) compared with
      patients treated before EPT became available. A subanalysis among patients
      retested for gonorrhea within 90 and 30 days found retreatment rates of 18.8% (n
      = 91/485) and 13.5% (n = 19/140), respectively. The 90-day cohort showed no
      association with treatment regimen (aHR, 0.95 [0.55-1.65]); however, all of the
      retreated patients in the 30-day cohort had received the doxycycline regimen.
      CONCLUSIONS: Gonorrhea retreatment was common, highlighting the need for
      rescreening and better partner therapies. The protective effect of EPT further
      underscores the need for effective oral therapies. Azithromycin may be preferable
      as the second agent to treat gonorrhea, although doxycycline seems to be a
      reasonable alternative.

PMID- 23965768
TI  - Sexually transmitted infection prevalence in a population seeking no-cost
      contraception.
AB  - BACKGROUND: We used universal screening to determine the prevalence rates of
      Neisseria gonorrhoeae (GC), Chlamydia trachomatis (CT), and Trichomonas vaginalis
      (TV) in 9256 women enrolling into a contraceptive study. METHODS: We offered
      screening using nucleic acid amplification or culture to all participants
      enrolling into the Contraceptive CHOICE Project. Demographic characteristics were
      collected through staff-administered questionnaires. Univariate and multivariable
      analyses were performed to assess the risk of sexually transmitted infection at
      baseline and to compare risk profiles of CT and TV. RESULTS: Results were
      available for 8347 consenting women with satisfactory results; 656 (7.9%) were
      tested positive for 1 or more infections. Approximately one third of participants
      were older than 26 years, and half were identified as African American. There
      were 35 cases of GC for a prevalence of 0.4% (95% confidence interval [CI], 0.3
      0.6), 260 cases of CT for a prevalence of 3.1% (95% CI, 2.8-3.5), and 410 cases
      of TV for a prevalence of 4.9% (95% CI, 4.4-5.4). Black women were more likely to
      be tested positive (odds ratio, 3.95; 95% CI, 3.08-5.06) compared with white
      women and accounted for 81.3% of cases. T. vaginalis was more prevalent in black
      women (8.9%) compared with white women (0.9%). Older age was a risk factor for
      TV, whereas younger age was associated with CT. Of the 656 positive cases, 106
      (16%) were diagnosed in women older than 25 years, falling outside traditional
      screening guidelines. CONCLUSION: We found GC, CT, and TV to be more prevalent
      than current national statistics, with TV being the most prevalent. Current
      screening recommendations would have missed 16% of infected women.

PMID- 23965769
TI  - Feasibility and acceptability of a novel cervicovaginal lavage self-sampling
      device among women in Kigali, Rwanda.
AB  - The Delphi Screener is a novel cervicovaginal lavage self-sampling device. Sixty
      women in Kigali (Rwanda) assessed the Screener at 2 consecutive visits. Between
      the visits, ease of use improved, reported difficulties decreased, and the
      collected sample weight increased. Most women preferred self-collection over a
      speculum examination. 

PMID- 23965770
TI  - Neisseria gonorrhoeae outbreak: unintended consequences of electronic medical
      records and using an out-of-state laboratory-California, July 2009-February 2010.
AB  - Twenty of 37 gonorrhea cases identified during an outbreak were diagnosed at one
      health care organization that used an out-of-state laboratory. The results were
      transmitted into electronic medical records without provider notification. Delays
      in treatment and reporting were identified. Systems should be implemented to
      ensure provider notification of electronic laboratory results. 

PMID- 23965771
TI  - Financial implications of male circumcision scale-up for the prevention of HIV
      and other sexually transmitted infections in a sub-Saharan African community.
AB  - BACKGROUND: The financial implications of male circumcision (MC) scale-up in sub
      Saharan Africa associated with reduced HIV have been evaluated. However, no
      analysis has incorporated the expected reduction of a comprehensive set of other
      sexually transmitted infections including human papillomavirus, herpes simplex
      virus type 2, genital ulcer disease, bacterial vaginosis, and trichomoniasis.
      METHODS: A Markov model tracked a dynamic population undergoing potential MC
      scale-up, as individuals experienced MC procedures, procedure-related adverse
      events, and MC-reduced sexually transmitted infections and accrued any associated
      costs. Rakai, Uganda, was used as a prototypical rural sub-Saharan African
      community. Monte Carlo microsimulations evaluated outcomes under 4 alternative
      scale-up strategies to reach 80% MC coverage among men aged 15 to 49 years, in
      addition to a baseline strategy defined by current MC rates in central Uganda.
      Financial outcomes included direct medical expenses only and were evaluated over
      5 and 25 years. Costs were discounted to the beginning of each period, coinciding
      with the start of MC scale-up, and expressed in US $2012. RESULTS: Cost savings
      from infections averted by MC vary from US $197,531 after 5 years of a scale-up
      program focusing on adolescent/adult procedures to more than US $13 million after
      25 years, under a strategy incorporating increased infant MCs. Over a 5-year
      period, reduction in HIV contributes to 50% of cost savings, and for 25 years,
      this contribution rises to nearly 90%. CONCLUSIONS: Sexually transmitted
      infections other than HIV contribute to cost savings associated with MC scale-up.
      Previous analyses, focusing exclusively on the financial impact through averted
      HIV, may have underestimated true cost savings by 10% to 50%.

PMID- 23965772
TI  - In Peru, reporting male sex partners imparts significant risk of incident
      HIV/sexually transmitted infection: all men Engaging in same-sex behavior need
      prevention services.
AB  - BACKGROUND: Detailed information on the sexual behavior of bisexual, non-gay
      identified men and the relationship between same-sex behavior and HIV/sexually
      transmitted infection (STI) incidence is limited. This study provides information
      on the sexual behavior with male partners of non-gay-identified men in urban,
      coastal Peru and the relationship of this behavior with HIV/STI incidence.
      METHODS: We analyzed data from 2146 non-gay-identified men with a baseline and
      then 2 years of annual follow-up, including detailed information on sexual
      behavior with up to 5 sex partners, to determine the characteristics associated
      with bisexual behavior. Discrete time proportional hazards models were used to
      determine the effect of self-reported sex with men on subsequent HIV/STI
      incidence. RESULTS: Over the 3 study visits, sex with a man was reported by 18.9%
      of men, 90% of whom also reported sex with a female partner. At baseline,
      reported bisexual behavior was associated with other sexual risk behaviors such
      as exchanging sex for money and increased risk of HIV, herpes simplex virus type
      2, and gonorrhea. The number of study visits in which recent sex with men was
      reported was positively correlated with risk of other sexual risk behaviors and
      incident HIV, herpes simplex virus type 2, and gonorrhea. Recent sex with a man
      was associated with increased HIV/STI incidence (hazard ratio, 1.79; confidence
      interval, 1.19-2.70), after adjusting for sociodemographics and other sexual risk
      behaviors. CONCLUSIONS: Given the prevalence of recent sex with men and the
      relationship of this behavior with HIV/STI incidence, interventions with non-gay
      identified men who have sex with men and their partners are warranted.

PMID- 23965773
TI  - Socioeconomic disparities in sexually transmitted infections among young adults
      in the United States: examining the interaction between income and
      race/ethnicity.
AB  - BACKGROUND: There is considerable evidence of racial/ethnic patterning of
      sexually transmitted infection (STI) risk in the United States. There is also
      evidence that poorer persons are at increased STI risk. Evidence regarding the
      interaction of race/ethnicity and income is limited, particularly nationally at
      the individual level. METHODS: We examined the pattern of socioeconomic gradients
      in STI infection among young people in a nationwide US study and determined how
      these gradients varied by race/ethnicity. We estimated the cumulative diagnosis
      prevalence of chlamydia, gonorrhea, or trichomoniasis (via self-report or
      laboratory confirmation) for young adults (ages, 18-26 years old) Hispanics and
      non-Hispanic whites, blacks, and others across income quintiles in the Add Health
      data set. We ran regression models to evaluate these relationships adjusting for
      individual- and school-level covariates. RESULTS: Sexually transmitted infection
      diagnosis was independently associated with both racial/ethnic identity and with
      low income, although the racial/ethnic disparities were much larger than income
      based ones. A negative gradient of STI risk with increasing income was present
      within all racial/ethnic categories, but was stronger for nonwhites. CONCLUSIONS:
      Both economic and racial/ethnic factors should be considered in deciding how to
      target STI prevention efforts in the United States. Particular focus may be
      warranted for poor, racial/ethnic minority women.

PMID- 23965774
TI  - Do only 21% of HIV-positive Medicaid enrollees link to treatment? Challenges in
      interpreting medicaid claims data.

PMID- 23965775
TI  - Response to Leibowitz et al.

PMID- 23965776
TI  - High-risk human papillomavirus messenger RNA testing in physician- and self
      collected specimens for cervical lesion detection in high-risk women, Kenya.
AB  - BACKGROUND: Little is known about the performance of physician-versus self
      collected specimens for high-risk human papillomavirus (hrHPV) messenger RNA
      (mRNA) testing or risk factors for hrHPV mRNA positivity in physician- versus
      self-collected specimens. We compared the performance of hrHPV mRNA testing of
      physician- and self-collected specimens for detecting cytological high-grade
      squamous intraepithelial lesions or more severe (>=HSIL) and examined risk
      factors for hrHPV mRNA positivity in female sex workers in Nairobi. METHODS: From
      2009 to 2011, 344 female sex workers participated in this cross-sectional study.
      Women self-collected a cervicovaginal specimen. A physician conducted a pelvic
      examination to obtain a cervical specimen. Physician- and self-collected
      specimens were tested for hrHPV mRNA and sexually transmitted infections using
      APTIMA nucleic acid amplification assays (Hologic/Gen-Probe Incorporated, San
      Diego, CA). Cervical cytology was conducted using physician-collected specimens
      and classified according to the Bethesda criteria. RESULTS: Overall hrHPV mRNA
      prevalence was similar in physician- and self-collected specimens (30% vs. 29%).
      Prevalence of >=HSIL was 4% (n = 15). Overall sensitivity of hrHPV testing for
      detecting >=HSIL was similar in physician-collected (86%; 95% CI, 62%-98%; 13
      cases detected) and self-collected specimens (79%; 95% CI, 55%-95%; 12 cases
      detected). Overall specificity of hrHPV mRNA for >=HSIL was similar in both
      physician-collected (73%; 95% CI, 68%-79%) and self-collected (75%; 95% CI, 70%
      79%) specimens. High-risk HPV mRNA positivity in both physician- and self
      collected specimens seemed higher in women who were younger (<30 years), had
      Trichomonas vaginalis or Mycoplasma genitalium infections, or had more than 8
      years of educational attainment. CONCLUSIONS: Self-collected specimens for hrHPV
      mRNA testing seemed to have similar sensitivity and specificity as physician
      collected specimens for the detection of >=HSIL among high-risk women.

PMID- 23965777
TI  - Sexually transmitted diseases among persons with HIV with low viral load.

PMID- 23965778
TI  - Prevalence and type distribution of human papillomavirus among 1813 men in
      Tanzania and the relationship to HIV status.
AB  - BACKGROUND: Infection with high-risk (HR) human papillomavirus (HPV) is
      associated with penile cancer in men, cervical cancer in women, and anal cancer
      and certain types of head and neck cancers in both sexes. Few studies have
      assessed the prevalence and type distribution of HPV among men in sub-Saharan
      Africa, where the rates of HIV and penile and cervical cancer are high. MATERIAL
      AND METHODS: We used data from a cross-sectional study among 1813 men in
      Tanzania. Penile samples were tested using Hybrid Capture 2, and genotyping was
      done by the INNO-LiPA HPV Genotyping Extra test. Blood samples were tested for
      HIV. The overall and type-specific prevalence and 95% confidence interval of HPV
      was estimated in relation to age and HIV status. RESULTS: The overall prevalence
      of HPV was 20.5% (95% confidence interval, 18.7-22.4), the most prevalent HR HPV
      types being HPV52, HPV51, HPV16, HPV18, HPV35, and HPV66. The HR HPV prevalence
      was significantly higher in HIV-positive men (25.7%) than in HIV-negative men
      (15.8%; P = 0.0027). The prevalence of HPV16, HPV18 and multiple HR HPVs tended
      to be higher among HIV-positive men (statistically nonsignificant), whereas no
      differences were observed for the other HPV types. CONCLUSIONS: We found a high
      prevalence of HPV types 52, 51, 16, 18, 35, and 66. This information is of
      relevance in the understanding of HPV type distributions across populations.
      Although the prevalence of HPV16 and HPV18 was slightly higher among HIV-positive
      men, our results indicate that HIV status does not strongly influence the
      distribution of HPV types. Therefore, the currently available HPV vaccines could
      prevent HPV infection independently of HIV status.

PMID- 23965779
TI  - Gonorrhea positivity in New Orleans public high schools, 1996 to 2005.

PMID- 23965780
TI  - Human papillomavirus seropositivity and subsequent risk of HIV acquisition in
      rural South African women.
AB  - OBJECTIVE: This study aimed to provide a population-based estimate of human
      papillomavirus (HPV) seropositivity for women in a rural African context and to
      evaluate the impact of HPV serostatus on subsequent acquisition of HIV outside a
      clinical setting. DESIGN: A random sample of women participating in a
      longitudinal, population-based HIV survey combined with a case-control study.
      METHODS: Blood samples of women participating in a single round of population
      based HIV surveillance (N = 1049) in a rural South African population were used
      to measure vaccine-preventable HPV seropositivity (types 6, 11, 16, and 18) in
      the general population in 2010. Using results from the repeat HIV surveys, a case
      control analysis was then performed comparing HPV sero-status in samples taken
      from HIV sero-converting women (prior to infection with HIV) against samples from
      HIV-uninfected, sexually-active controls matched 1:1 according to 5-year age band
      (377:377). Unconditional multivariable logistic regression with multiple
      imputations was used to control for sociodemographic and behavioral variables
      associated with HIV acquisition. RESULTS: Human papillomavirus seropositivity in
      the population-based sample of women was 20.8% (95% confidence interval [CI],
      18.3-23.4), and HIV prevalence was 27.6% (95% CI, 24.9-30.4). In the case-control
      analysis, allowing for variables known to be associated with HIV incidence, HPV
      seropositivity was associated with nearly 2.5 times the odds of subsequent
      acquisition of HIV (adjusted odds ratio, 2.33 [95% CI, 1.61-3.39]; P < 0.001).
      CONCLUSIONS: These results suggest that HPV vaccination before or soon after
      sexual debut could lower HIV infection risk. Randomized trials that quantify the
      impact of HPV vaccination in girls on the risk of acquiring HIV are urgently
      required.

PMID- 23965781
TI  - Underreporting of viral encephalitis and viral meningitis, Ireland, 2005-2008.
AB  - Viral encephalitis (VE) and viral meningitis (VM) have been notifiable infectious
      diseases under surveillance in the Republic of Ireland since 1981. Laboratories
      have reported confirmed cases by detection of viral nucleic acid in cerebrospinal
      fluid since 2004. To determine the prevalence of these diseases in Ireland during
      2005-2008, we analyzed 3 data sources: Hospital In-patient Enquiry data (from
      hospitalized following patients discharge) accessed through Health Intelligence
      Ireland, laboratory confirmations from the National Virus Reference Laboratory,
      and events from the Computerised Infectious Disease Reporting surveillance
      system. We found that the national surveillance system underestimates the
      incidence of these diseases in Ireland with a 10-fold higher VE hospitalization
      rate and 3-fold higher VM hospitalization rate than the reporting rate.
      Herpesviruses were responsible for most specified VE and enteroviruses for most
      specified VM from all 3 sources. Recommendations from this study have been
      implemented to improve the surveillance of these diseases in Ireland. 

PMID- 23965782
TI  - Pharmacometric Analyses to Support Early Development Decisions for LY2878735: A
      Novel Serotonin Norepinephrine Reuptake Inhibitor.
AB  - LY2878735 is a novel dual serotonin (5-hydroxytryptamine (5-HT)) and
      norepinephrine (NE) reuptake inhibitor (SNRI) in development for chronic pain
      indications. In vitro profile suggests a more balanced profile as compared with
      other SNRI's, which is expected to confer superior clinical efficacy. LY2878735
      is metabolized partly by the genetically polymorphic cytochrome P450 (CYP) 2D6
      pathway, raising pharmacokinetic (PK) variability concerns. Phase 1 PK and
      biomarker data were analyzed by pharmacometric methods to characterize the
      balance between dual-target engagement and adverse effects on heart rate (HR) and
      blood pressure (BP). A narrow range of plasma LY2878735 levels was associated
      with an acceptable balance. As compared with poor metabolizers (PM), CYP2D6
      extensive metabolizers (EM) have 21- and threefold higher clearance and
      distribution volume, respectively. Even with a CYP2D6-based dosing paradigm, a
      superior therapeutic index comparable to duloxetine, a widely used SNRI, was not
      achievable and LY2878735 development was thus terminated. Model-based approach
      effectively synthesizes PK-pharmacodynamic (PD) relationships, enabling efficient
      early development decisions.CPT: Pharmacometrics & Systems Pharmacology (2013) 2,
      e66; doi:10.1038/psp.2013.43; published online 21 August 2013. 

PMID- 23965783
TI  - Use of a biomarker in exposure-response analysis to support dose selection for
      fingolimod.
AB  - Fingolimod 0.5 mg q.d. (once daily) has been approved for the treatment of
      patients with relapsing and remitting forms of multiple sclerosis (RRMS).
      Fingolimod at two doses (0.5 and 1.25 mg) showed superior effectiveness in the
      frequency of relapse with little difference between the two dose groups. At the
      same time, fingolimod manifests a number of dose-dependent adverse events. Given
      the safety concerns and similar effect size at both dose groups, it was
      reasonable to raise the question whether doses even lower than 0.5 mg would
      produce sufficient effectiveness. Therefore, our analysis focused on estimating
      the effect size of the primary endpoint at doses lower than 0.5 mg via exposure
      response analysis. Specifically, we aim to show how biomarker data can be used as
      a bridge in exposure-response analysis to estimate the clinical endpoint response
      at certain doses when the direct relationship between exposure and the clinical
      endpoint can not be quantified reliably.CPT: Pharmacometrics & Systems
      Pharmacology (2013) 2, e67; doi:10.1038/psp.2013.44; published online 21 August
      2013. 

PMID- 23965784
TI  - Systems approaches evolve clinical pharmacology.

PMID- 23965786
TI  - [Development of temporal subtraction method for chest radiographs by using pixel
      matching technique].
AB  - A temporal subtraction image, which is obtained by subtraction of a previous
      image from a current one, can enhance interval changes on a chest radiograph by
      removal of most normal structures. However, subtraction artifacts, which tend to
      reduce its effectiveness in the detection of interval changes, were still
      included in the conventional method. In this study, we have developed a pixel
      matching technique to reduce artifacts in the temporal subtraction images. With
      this technique, the pixel value in a nonlinearly warped previous image is
      replaced by a pixel value within a kernel, which is closest to the pixel value on
      a current image. For evaluation of the proposed method, one hundred temporal
      subtraction images with a simulated nodule were used. When the kernel size of 3*3
      was employed in the pixel matching technique, the misregistration artifacts
      decreased by 72%, and the contrast-to-noise ratio of the simulated lung nodules
      was increased by 5% in comparison with the conventional method. However, the area
      of the simulated nodule on the subtraction image decreased by 6%. Our results
      indicated that the pixel matching technique can enhance simulated nodules, with a
      substantial reduction of misregistration artifacts in comparison with
      conventional subtraction images. Therefore, we believe that the temporal
      subtraction method with the pixel matching technique would assist radiologists'
      diagnoses for detection of lung nodules in digital chest radiography. 

PMID- 23965785
TI  - Wall teichoic acid structure governs horizontal gene transfer between major
      bacterial pathogens.
AB  - Mobile genetic elements (MGEs) encoding virulence and resistance genes are
      widespread in bacterial pathogens, but it has remained unclear how they
      occasionally jump to new host species. Staphylococcus aureus clones exchange MGEs
      such as S. aureus pathogenicity islands (SaPIs) with high frequency via helper
      phages. Here we report that the S. aureus ST395 lineage is refractory to
      horizontal gene transfer (HGT) with typical S. aureus but exchanges SaPIs with
      other species and genera including Staphylococcus epidermidis and Listeria
      monocytogenes. ST395 produces an unusual wall teichoic acid (WTA) resembling that
      of its HGT partner species. Notably, distantly related bacterial species and
      genera undergo efficient HGT with typical S. aureus upon ectopic expression of S.
      aureus WTA. Combined with genomic analyses, these results indicate that a
      'glycocode' of WTA structures and WTA-binding helper phages permits HGT even
      across long phylogenetic distances thereby shaping the evolution of Gram-positive
      pathogens. 

PMID- 23965787
TI  - [Proposal for contrast-amplified image reconstruction methods by adjusting
      computed tomography value scale in three-dimensional image processing].
AB  - To create three-dimensional computed tomography angiography (3D-CTA) images of
      blood vessels, it is important to acquire a high-contrast original image of the
      blood vessels and the surrounding tissues. However, reexamination is likely to be
      needed if, due to the condition of the examinee, insufficient contrast
      enhancement is achieved. This prompted us to design a method of amplifying image
      contrast using software that simply adds the CT value to each corresponding pixel
      of the original image, i.e., the same image is added after the scan. This
      prevents spatial and time discontinuities with the original image. The CT value
      of the original image can also be increased arbitrarily to any value by adjusting
      the weighting level of the added image. The difference in CT values between the
      pixels can thus be amplified without changing the contours of the original image.
      Since this method enables the original image's contrast to be amplified by post
      processing, i.e., without increasing radiation load exposure or employing
      additional contrast medium, it is a technique with high clinical utility. 

PMID- 23965788
TI  - [Influence of heart rhythm, breathing and arm position during computed tomography
      scanning on the registration accuracy of electro anatomical map (EAM) images,
      left atrium three-dimensional computed tomography angiography images, and
      fluoroscopy time during ablation to treat atrial fibrillation].
AB  - BACKGROUND: In CARTOMERGE((r)) for treatment of atrial fibrillation (AF) by
      ablation, by integrating electro anatomical map (EAM) and left atrium three
      dimensional computed tomography angiography (3D-CTA) images, identification of
      the ablation points is simplified and the procedure can be made carried out more
      rapidly. However, the influence that heart rhythm, breathing and arm position
      during CT scanning have on registration accuracy and fluoroscopy time is not
      clear. PURPOSE: To clarify the influence on registration accuracy and fluoroscopy
      time of heart rhythm, breathing and arm position during CT scanning. METHODS: The
      patients were CT-scanned during both sinus rhythm (SR) and AF in each study
      subject. We evaluated the registration accuracy of images reconstructed between
      the cardiac cycle and assessed the registration accuracy and fluoroscopy time of
      images obtained during inspiratory breath-hold, expiratory breath-hold and up and
      down position of the arm. RESULTS: Although the registration accuracy of the EAM
      image and left atrium 3D-CTA image showed a significant difference during SR, no
      significant difference was seen during AF. Expiratory breath-hold and down
      position of the arm resulted in the highest registration accuracy and the
      shortest fluoroscopy time. However, arm position had no significant effect on
      registration accuracy. CONCLUSIONS: Heart rhythm and breathing during CT scanning
      have a significant effect on the registration accuracy of EAM images, left atrium
      3D-CTA images, and fluoroscopy time.

PMID- 23965789
TI  - [Abbreviations of special terms for presentation/paper titles in magnetic
      resonance study].
AB  - PURPOSE: A large number of abbreviations have been created for various special
      terms, and used in magnetic resonance (MR) study. However, the use of these
      abbreviations in the paper title has been restricted by the majority of societies
      and journals. In this study, we investigated the use of various abbreviations for
      special terms in MR study in order to clarify which abbreviation could be used in
      the paper title without spelling. MATERIALS AND METHODS: We used two journals,
      Magnetic Resonance in Medicine (MRM) and Journal of Magnetic Resonance Imaging
      (JMRI) published by the International Society for Magnetic Resonance in Medicine
      (ISMRM), which has been considered to be the most advanced society for MR study
      in the world, as the reference standard for use of the abbreviations. RESULTS:
      Except for some basic abbreviations and specific abbreviations that were used on
      a long-term basis, the majority of abbreviations were used in the paper title
      with its full spelling in order to ensure generality. CONCLUSION: It is
      preferable that abbreviations not be used in the title of the or title of the
      paper.

PMID- 23965790
TI  - [Comparing multiple groups -non-parametric analysis-].

PMID- 23965791
TI  - [Operation support using three-dimensional computed tomography images: surgical].

PMID- 23965792
TI  - [Ultrasonographic assessment of the ischemic heart disease].

PMID- 23965794
TI  - [About the relationship between the IEC Standard (IEC 62563-1) and Quality
      Assurance (QA)Guidelines for Medical Imaging Display Systems (JESRA X-0093)].

PMID- 23965795
TI  - [My experience in Nagoya with radiological technology].

PMID- 23965797
TI  - The Journal of Nursing Research is particularly international.

PMID- 23965798
TI  - The relationship between anagliptin concentration showing over 80% inhibition of
      plasma dipeptidyl peptidase-4 activity and its protective effect against glucagon
      like peptide-1 degradation.
AB  - In dipeptidyl peptidase-4 (DPP-4) inhibitors, the inhibition of plasma DPP-4
      activity by 80% is considered sufficient to have an effect on glycemic control
      improvement through the elevation of intact glucagon-like peptide-1 (GLP-1). To
      clarify whether or not the 80% inhibition is sufficient to protect against GLP-1
      degradation, we investigated rats with a continuous infusion of exogenous GLP-1.
      When GLP-1 was infused into the femoral or portal vein, the steady state active
      GLP-1 levels in plasma significantly increased (P<0.05) at the 80% inhibitory
      concentration (IC80) of anagliptin (a highly selective DPP-4 inhibitor) against
      plasma DPP-4 activity, compared with control. In addition, the peptide levels
      increased in a concentration-dependent manner at drug concentrations from IC80 to
      10-fold IC80, and the levels at the 10-fold IC80 were significantly higher
      (P<0.05) than those at IC80. The concentration dependency on GLP-1 increment was
      also confirmed based on the experiment in which the endogenous active GLP-1
      levels were measured after an oral carbohydrate load. These findings suggest that
      an almost complete inhibition (80%) of plasma DPP-4 activity was insufficient to
      protect GLP-1 degradation, and much higher drug concentrations such as 10-fold
      IC80 are necessary to potently protect GLP-1 from degradation by DPP-4 commonly
      present in blood and tissues. 

PMID- 23965799
TI  - Design, synthesis and anticonvulsant activity evaluation of novel 4-(4
      substitutedphenyl)-3-methyl-1H-1,2,4-triazol-5(4H)-ones.
AB  - A series of novel 4-(4-substitutedphenyl)-3-methyl-1H-1,2,4-triazol-5(4H)-one
      derivatives were synthesized and screened for their anticonvulsant activities by
      the maximal electroshock test (MES) and their neurotoxicity was evaluated by the
      rotarod neurotoxicity test (TOX). In the MES test, compound 4-{4-[(3
      fluorobenzyl)oxy]phenyl}-3-methyl-1H-1,2,4-triazol-5(4H)-one (4n) was found to
      possess better anticonvulsant activity and higher safety than marketed drugs
      Carbamazepine with an ED50 value of 25.5 mg/kg and protective index (PI)
      value>48.8. In addition, the potency of compound 4n against seizures induced by
      Pentylenetetrazole, 3-Mercaptopropionic acid, and Bicuculline suggested its broad
      spectrum activity, and the mechanisms of action including inhibition of voltage
      gated ion channels and modulation of GABAergic activity might involve in its
      anticonvulsant activity. 

PMID- 23965800
TI  - Evaluation of radiochromic gel dosimetry and polymer gel dosimetry in a clinical
      dose verification.
AB  - A quantitative comparison of two full three-dimensional (3D) gel dosimetry
      techniques was assessed in a clinical setting: radiochromic gel dosimetry with an
      in-house developed optical laser CT scanner and polymer gel dosimetry with
      magnetic resonance imaging (MRI). To benchmark both gel dosimeters, they were
      exposed to a 6 MV photon beam and the depth dose was compared against a diamond
      detector measurement that served as golden standard. Both gel dosimeters were
      found accurate within 4% accuracy. In the 3D dose matrix of the radiochromic gel,
      hotspot dose deviations up to 8% were observed which are attributed to the
      fabrication procedure. The polymer gel readout was shown to be sensitive to B0
      field and B1 field non-uniformities as well as temperature variations during
      scanning. The performance of the two gel dosimeters was also evaluated for a
      brain tumour IMRT treatment. Both gel measured dose distributions were compared
      against treatment planning system predicted dose maps which were validated
      independently with ion chamber measurements and portal dosimetry. In the
      radiochromic gel measurement, two sources of deviations could be identified.
      Firstly, the dose in a cluster of voxels near the edge of the phantom deviated
      from the planned dose. Secondly, the presence of dose hotspots in the order of
      10% related to inhomogeneities in the gel limit the clinical acceptance of this
      dosimetry technique. Based on the results of the micelle gel dosimeter prototype
      presented here, chemical optimization will be subject of future work. Polymer gel
      dosimetry is capable of measuring the absolute dose in the whole 3D volume within
      5% accuracy. A temperature stabilization technique is incorporated to increase
      the accuracy during short measurements, however keeping the temperature stable
      during long measurement times in both calibration phantoms and the volumetric
      phantom is more challenging. The sensitivity of MRI readout to minimal
      temperature fluctuations is demonstrated which proves the need for adequate
      compensation strategies. 

PMID- 23965802
TI  - Cardiac dysfunction in mitochondrial disease. Clinical and molecular features.
AB  - BACKGROUND: Mitochondrial disorders (MD) are multisystem diseases that arise as a
      result of dysfunction of the oxidative phosphorylation system. The predominance
      of neuromuscular manifestations in MD could mask the presence of other clinical
      phenotypes such as cardiac dysfunction. Reported here is a retrospective study,
      the main objective of which was to characterize the clinical and molecular
      features of a cohort of patients with cardiomyopathy and MD. METHODS AND RESULTS:
      Hospital charts of 2,520 patients, evaluated for presumed MD were reviewed. The
      clinical criterion for inclusion in this study was the presence of a cardiac
      disturbance accompanied by a mitochondrial dysfunction. Only 71 patients met this
      criterion. The mitochondrial genome (mtDNA) could be sequenced only in 45 and the
      pathogenicity of 2 of the found changes was investigated using transmitochondrial
      cybrids. Three nucleotide changes in mtDNA that may be relevant and 3 with
      confirmed pathogenicity were identified but no mutations were found in the 13
      nuclear genes analyzed. CONCLUSIONS: The mtDNA should be sequenced in patients
      with cardiac dysfunction accompanied by symptoms suggestive of MD; databases
      should be carefully and periodically screened to discard mitochondrial variants
      that could be associated with MD; functional assays are necessary to classify
      mitochondrial variants as pathogenic or polymorphic; and additional efforts must
      be made in order to identify nuclear genes that can explain some as yet
      uncharacterized molecular features of mitochondrial cardiomyopathy.

PMID- 23965801
TI  - Vascular endothelial sigma1-receptor stimulation with SA4503 rescues aortic
      relaxation via Akt/eNOS signaling in ovariectomized rats with aortic banding.
AB  - BACKGROUND: We previously reported that sigma1-receptor (sigma1R) expression in
      the thoracic aorta decreased after pressure overload (PO) induced by abdominal
      aortic banding in ovariectomized (OVX) rats. Here, we asked whether stimulation
      of sigma1R with the selective agonist SA4503 elicits functional recovery of
      aortic vasodilation and constriction following vascular injury in OVX rats with
      PO. METHODS AND RESULTS:  SA4503 (0.3-1.0mg/kg) and NE-100 (a sigma1R antagonist,
      1.0mg/kg) were administered orally for 4 weeks (once daily) to OVX-PO rats.
      Vascular functions of isolated descending aorta were measured following
      phenylephrine (PE)- or endothelin-1 (ET-1)-induced vasoconstriction and
      acetylcholine (ACh)- or clonidine-induced vasodilation. SA4503 administration
      rescued PO-induced sigma1R decreases in aortic smooth muscle and endothelial
      cells. SA4503 treatment also rescued PO-induced impairments in ACh- and clonidine
      induced vasodilation without affecting PE- and ET-1-induced vasoconstriction.
      Ameliorated ACh- and clonidine-induced vasodilation was closely associated with
      increased Akt activity and in turn endothelial nitric oxide synthase (eNOS)
      phosphorylation. The SA4503-mediated improvement of vasodilation was blocked by
      NE-100 treatment. CONCLUSIONS:  sigma1R is downregulated following PO-induced
      endothelial injury in OVX rats. The selective sigma1R agonist SA4503 rescues
      impaired endothelium-dependent vasodilation in the aorta from OVX-PO rats through
      sigma1R stimulation, enhancing eNOS-cGMP signaling in vascular endothelial cells.
      These observations encourage development of novel therapeutics targeting sigma1R
      to prevent vascular endothelial injury in vascular diseases.

PMID- 23965804
TI  - Did she suffer?

PMID- 23965803
TI  - Mdig de-represses H19 large intergenic non-coding RNA (lincRNA) by down
      regulating H3K9me3 and heterochromatin.
AB  - Mineral dust-induced gene (mdig) had been linked to the development of human lung
      cancers associated with environmental exposure to mineral dust, tobacco smoke or
      other carcinogens. In the present studies, we demonstrated that the
      overexpression of mdig in A549 adenocarcinomic human alveolar type II epithelial
      cells decreases the heterochromatin conformation of the cells and de-represses
      the transcription of genes in the tandemly repeated DNA regions. Although mdig
      can only cause a marginal decrease of the total histone H3 lysine 9
      trimethylation (H3K9me3), a significant reduction of H3K9me3 in the promoter
      region of H19, the paternally imprinted but maternally expressed gene
      transcribing a large intergenic non-coding RNA (lincRNA), was observed in the
      cells with mdig overexpression. Silencing mdig by either shRNA or siRNA not only
      increased the level of H3K9me3 in the promoter region of H19 but also attenuated
      the transcription of H19 long non-coding RNA. Demethylation assays using
      immunoprecipitated mdig and histone H3 peptide substrate suggested that mdig is
      able to remove the methyl groups from H3K9me3. Clinically, we found that higher
      levels of mdig and H19 expression correlate with poorer survival of the lung
      cancer patients. Taken together, our results imply that mdig is involved in the
      regulation of H3K9me3 to influence the heterochromatin structure of the genome
      and the expression of genes important for cell growth or transformation. 

PMID- 23965805
TI  - Cost-effectiveness impact of rivaroxaban versus new and existing prophylaxis for
      the prevention of venous thromboembolism after total hip or knee replacement
      surgery in France, Italy and Spain.
AB  - Venous thromboembolism (VTE) has a significant impact on healthcare costs but is
      largely preventable with anticoagulant prophylaxis using low-molecular-weight
      heparins (LMWHs), such as enoxaparin or dalteparin. Rivaroxaban and dabigatran
      etexilate are two new oral anticoagulants (NOACs) both compared with enoxaparin
      in separate trials. A decision analytic model with a healthcare and national
      payer perspective over a five-year time horizon was used to evaluate the cost
      effectiveness of the NOACs for VTE prophylaxis after total hip replacement (THR)
      or total knee replacement (TKR) in France, Italy and Spain. Efficacy and safety
      data were obtained from randomised controlled trials of rivaroxaban vs enoxaparin
      and an indirect statistical comparison for rivaroxaban vs dabigatran. Rivaroxaban
      demonstrated dominance across all comparisons, indications and countries. In THR,
      total per-patient costs were reduced by up to ?160 in the enoxaparin comparison
      and ?115 in the dabigatran comparison, respectively. In addition, quality
      adjusted life-years (QALYs) were increased by up to 0.0011 and 0.0012 in each
      comparison, respectively. Similarly, total costs were reduced in TKR by up to
      ?137 and ?28 in the enoxaparin and dabigatran comparisons, respectively. The
      total number of QALYs was increased by up to 0.0014 in the enoxaparin comparison
      and 0.0005 in the dabigatran comparison. The results were driven by costs since
      the incremental benefits were minimal. Rivaroxaban use could result in
      substantial healthcare cost savings and improved quality of life. The results are
      applicable across three European countries with differing healthcare systems so,
      potentially, could be generalised to a much wider population. 

PMID- 23965806
TI  - Work-home interference and its prospective relation to major depression and
      treatment with antidepressants.
AB  - OBJECTIVES: Few longitudinal studies have investigated if "work-home
      interference" (WHI), conflicts between work and home demands, predicts depressive
      disorders. We examined if WHI was prospectively associated with indicators of
      major depression in a nationally representative sample. METHODS: We used multiple
      logistic and Cox regression models to examine if self-reported WHI was related to
      probable major depression [scoring high on a brief self-report scale based on the
      (Hopkins) Symptom Checklist] and/or any new antidepressant treatment using the
      prescribed drug register during a 2-year follow-up. The analytic sample comprised
      1576 men and 1678 women, working respondents to the Swedish Longitudinal
      Occupational Survey of Health (SLOSH), free of major depression and prior
      purchases of antidepressants at baseline. RESULTS: Altogether, 7% experienced
      high (very often/the whole time) and 32% moderate (sometimes) WHI. Overall, the
      analyses indicated prospective associations between especially high WHI and major
      depression and/or antidepressant treatment also when adjusting for work
      characteristics (demands, control, support, overtime). However, the estimates for
      major depression differed by sex. Separate analyses indicated that only women
      with high WHI were significantly more likely to have subsequent major depression.
      Analyses further indicated an elevated rate of antidepressant treatment for men
      in particular, partly explained by work characteristics and that major depression
      was related to subsequent high WHI. CONCLUSIONS: Based on a two-year follow-up,
      this study indicated that high WHI prospectively predicted major depression
      and/or antidepressant treatment, though effects appeared to differ to some extent
      by sex.

PMID- 23965807
TI  - High rates of Mycobacterium tuberculosis among socially marginalized immigrants
      in low-incidence area, 1991-2010, Italy.
AB  - Migration from low- and middle-income countries to high-income countries
      increasingly determines the severity of tuberculosis (TB) cases in the adopted
      country. Socially marginalized groups, about whom little is known, may account
      for a reservoir of TB among the immigrant populations. We investigated the rates
      of and risk factors for Mycobacterium tuberculosis transmission, infection, and
      disease in a cohort of 27,358 socially marginalized immigrants who were
      systematically screened (1991-2010) in an area of Italy with low TB incidence.
      Overall TB and latent TB infection prevalence and annual tuberculin skin testing
      conversion rates (i.e., incidence of new infection) were 2.7%, 34.6%, and 1.7%,
      respectively. Prevalence of both TB and latent TB infection and incidence of
      infection increased as a function of the estimated TB incidence in the
      immigrants' countries of origin. Annual infection incidence decreased with time
      elapsed since immigration. These findings have implications for control policy
      and immigrant screening in countries with a low prevalence of TB. 

PMID- 23965808
TI  - Highly pathogenic avian influenza A(H7N3) virus in poultry workers, Mexico, 2012.
AB  - We identified 2 poultry workers with conjunctivitis caused by highly pathogenic
      avian influenza A(H7N3) viruses in Jalisco, Mexico. Genomic and antigenic
      analyses of 1 isolate indicated relatedness to poultry and wild bird subtype H7N3
      viruses from North America. This isolate had a multibasic cleavage site that
      might have been derived from recombination with host rRNA. 

PMID- 23965809
TI  - Regulatory Forum commentary: alternative mouse models for future cancer risk
      assessment.
AB  - International regulatory and pharmaceutical industry scientists are discussing
      revision of the International Conference on Harmonisation of Technical
      Requirements for Registration of Pharmaceuticals for Human Use (ICH) S1 guidance
      on rodent carcinogenicity assessment of small molecule pharmaceuticals. A weight
      of-evidence approach is proposed to determine the need for rodent carcinogenicity
      studies. For compounds with high human cancer risk, the product may be labeled
      appropriately without conducting rodent carcinogenicity studies. For compounds
      with minimal cancer risk, only a 6-month transgenic mouse study (rasH2 mouse or
      p53+/- mouse) or a 2-year mouse study would be needed. If rodent carcinogenicity
      testing may add significant value to cancer risk assessment, a 2-year rat study
      and either a 6-month transgenic mouse or a 2-year mouse study is appropriate. In
      many cases, therefore, one rodent carcinogenicity study could be sufficient. The
      rasH2 model predicts neoplastic findings relevant to human cancer risk assessment
      as well as 2-year rodent models, produces fewer irrelevant neoplastic outcomes,
      and often will be preferable to a 2-year rodent study. Before revising ICH S1
      guidance, a prospective evaluation will be conducted to test the proposed weight
      of-evidence approach. This evaluation offers an opportunity for a secondary
      analysis comparing the value of alternative mouse models and 2-year rodent
      studies in the proposed ICH S1 weight-of-evidence approach for human cancer risk
      assessment. 

PMID- 23965810
TI  - [Antimicrobial resistance of Listeria monocytogenes strains of human and food
      origin in the Czech Republic].
AB  - BACKGROUND: To assess the incidence of antimicrobial resistance of L.
      monocytogenes strains isolated from humans and foods in the Czech Republic in the
      period of 2001 to 2012. MATERIAL AND METHODS: Phenotypic resistance testing has
      been monitored by the disk diffusion method and complemented by the assessment of
      minimum inhibitory concentration by E-test method and genes encoding resistance
      by the PCR method. RESULTS: All tested strains (678) were susceptible to
      ampicillin, penicillin, gentamicin, trimethoprim, vancomycin and chloramphenicol.
      Resistance to tetracycline (2/509) and erythromycin (1/509) was detected
      sporadically in strains of food origin. CONCLUSIONS: Very good and so far stable
      susceptibility of tested strains of L. monocytogenes isolated from humans and
      foods to antibiotics used in the therapy of listeriosis was found in the
      monitoring period. Sporadic occurrence of resistance was detected only in strains
      from foods.

PMID- 23965812
TI  - [Anisakiasis - a little-known parasitic zoonosis].
AB  - Parasites of the family Anisakidae cause enteric parasitic zoonoses developing
      after consumption of inadequately cooked marine fish. Cases of such diseases are
      reported mainly from Japan or other countries where raw or uncooked fish are
      traditionally consumed. The presented short communication briefly reports
      detection of larvae of Pseudoterranova spp., parasites of the family Anisakidae,
      in a fresh chilled angler-fish (Lophius piscatorius) bought at a retail store in
      the Czech Republic. 

PMID- 23965811
TI  - [News on Bartonella infections].
AB  - The review specifies 25 Bartonella species known so far and describes
      epidemiology and pathogenesis of Bartonella infections which are classified using
      patient symptomatology including culture-negative endocarditis. Microbiological
      diagnosis and significant principles of antibiotic therapy of Bartonella
      infections are also stated. 

PMID- 23965813
TI  - [Toxoplasmosis in pregnancy - questions in clinical practice].
AB  - Toxoplasmosis acquired during pregnancy is a serious disease that may
      significantly affect fetal development and cause irreversible or therapeutically
      hardly influenced damage to the newborn. Early and correct diagnosis of the
      disease in the mother is essential for determining prognosis and further
      diagnostic and therapeutic procedures. The case study combines a number of
      factors to be encountered in clinical practice which may complicate diagnostic
      considerations. One of them is the existence of a rare phenomenon of reinfection 
      its possible effects on prenatal screening and other interpretations of such
      findings. Another problem is the evaluation of the origin of sonographically
      confirmed fetopathy in relation to Toxoplasma etiology and the choice of next
      steps that should follow in this situation. Finally, the text discusses the
      selection of postnatal examinations so that they sufficiently contribute to
      decision-making about the newborn's treatment initiation. 

PMID- 23965814
TI  - [Effect of colistin consumption and prevalence of colistin-resistant bacteria].
AB  - OBJECTIVE: Recently, there has been a renaissance of the use of the antibiotic
      colistin resulting from increasing resistance of bacterial pathogens,
      particularly in intensive care patients. The study aimed at assessing the impact
      of colistin consumption on the prevalence of colistin-resistant bacteria in the
      University Hospital Olomouc (UHO). METHODS: A laboratory database was
      retrospectively searched to identify all clinically significant colistin
      resistant bacterial strains isolated between 2007 and 2011. These data were
      compared with colistin consumption over the same period and the results were
      statistically processed. RESULTS: Over the study period, a total of 6 338
      clinically significant colistin-resistant strains were detected in the UHO
      (Acinetobacter spp., Burkholderia cepacia complex, Citrobacter spp., Enterobacter
      spp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus spp.,
      Providencia spp., Pseudomonas spp., Serratia marcesces and Stenotrophomonas
      maltophilia). Over the same period, the consumption of colistin increased nearly
      10-fold. With the increasing colistin consumption, the numbers of colistin
      resistant strains of Pseudomonas aeruginosa and Acinetobacter spp. decreased over
      that period of time. By contrast, there was an increase in the rates of naturally
      Burkholderia cepacia complex strains naturally resistant to colistin. An alarming
      finding is that the prevalence of colistin-resistant strains of Klebsiella
      pneumoniae increased in the last years of the study period, especially in
      intensive care patients. CONCLUSIONS: In the UHO, higher consumption of colistin
      was accompanied by increased numbers of colistin-resistant strains. There was a
      marked increase of Burkholderia cepacia complex strains and, recently, a
      statistically insignificant but alarming increase in colistin-resistant
      Klebsiella pneumoniae strains.

PMID- 23965815
TI  - [Bacteria cleaving small-colony variants as causative agents of infective
      endocarditis and other severe diseases].
AB  - Small-colony variants (SCV) associated with specific biochemical features were
      described in many bacterial species. Bacteria with SCV phenotype have knocked out
      metabolic pathways for aerobic respiration, thus they behave like strict
      anaerobes. They are handicapped in competition for nutrients with other microbes
      but on the other hand they are able to resist some antibiotics and survive inside
      eucaryotic cells. Therefore they use to cause chronic and/or recurrent
      infections. Recovery of these infections is not possible without surgery. SCV
      phenotype seems to be a common life strategy for many bacteria. Its occurrence
      and clinical importance is similar to that of biofilm formation.

PMID- 23965816
TI  - Geography and the Medicaid mental health care infrastructure: implications for
      health care reform.
AB  - IMPORTANCE: Medicaid is the largest payer of mental health (MH) care in the
      United States, and this role will increase among states that opt into the
      Medicaid expansion. However, owing to the dearth of MH care providers who accept
      Medicaid, expanded coverage may not increase access to services. Facilities that
      provide specialty outpatient MH services and accept Medicaid compose the backbone
      of the community-based treatment infrastructure for Medicaid enrollees. For
      states that opt into the expansion, it is important to understand which local
      communities may face the greatest barriers to access these facilities. OBJECTIVE:
      To examine the availability of outpatient MH facilities that accept Medicaid
      across US counties and whether specific types of communities are more likely to
      lack this infrastructure. DESIGN, SETTING, AND PARTICIPANTS: Data from the 2008
      National Survey of Mental Health Treatment Facilities and Area Resource File were
      merged. A generalized ordered logistic regression with state fixed effects was
      estimated to examine determinants of accessibility of these facilities.
      Covariates included the percentages of residents who are black, Hispanic, living
      in poverty, and living in a rural area. MAIN OUTCOMES AND MEASURES: An ordered
      variable assessed whether a county had no access to outpatient MH facilities that
      accept Medicaid, intermediate access to these facilities (ie, >=1 facility, but
      not top quintile of facility to Medicaid enrollee per capita ratio), or high
      access (ie, top quintile of facility to Medicaid enrollee per capita ratio).
      RESULTS: More than one-third of counties do not have any outpatient MH facilities
      that accept Medicaid. Communities with a larger percentage of residents who are
      black (marginal effect [ME] = 3.9%; 95% CI, 1.2%-6.6%), Hispanic (ME = 4.8%; 95%
      CI, 2.3%-7.4%), or living in a rural area (ME = 27.9%; 95% CI, 25.3%-30.4%) are
      more likely to lack these facilities. CONCLUSIONS AND RELEVANCE: Many communities
      may face constraints on the MH safety-net system as Medicaid is expanded,
      especially rural communities and communities with a large percentage of black or
      Hispanic residents.

PMID- 23965817
TI  - Thermal stability of liquid antioxidative extracts from pomegranate peel.
AB  - BACKGROUND: Liquid extracts from pomegranate peel have the potential for use as
      natural antioxidant products. This study investigates the quality changes of
      liquid extracts before and after thermal treatment during sterilization and
      storage. Liquid pomegranate peel extracts were prepared, sterilized under ultra
      high temperature (UHT) at 121  degrees C for 10 s and then stored at three
      temperatures (4, 25 and 37  degrees C) for up to 180 days. The industrial, color,
      UV-visible spectrum profile and antioxidant (phenolics) characteristics were
      measured. RESULTS: Thermal sterilization treatment had no negative effects on the
      industrial, color, spectral and antioxidant characteristics of the extracts.
      After 180 days, the extracts stored at 4  degrees C retained 67% of the initial
      total soluble phenolic content and 58% of the original scavenging activity. The
      major antioxidant components in the extracts (stored at 4  degrees C for 180
      days) were gallic acid, punicalagin A, punicalagin B and ellagic acid having
      concentrations of 19.3, 197.2, 221.1 and 92.4 mg L-1, respectively. CONCLUSION:
      The results show that liquid pomegranate peel extracts had acceptable thermal
      stability after sterilization and storage. The recommended storage condition of
      this product was low temperature.

PMID- 23965818
TI  - Dr Elizabeth (Liz) Painter - Assistant Editor for Parasitology 1972-2013.

PMID- 23965820
TI  - Parasitism and phenotypic change in colonial hosts.
AB  - Changes in host phenotype are often attributed to manipulation that enables
      parasites to complete trophic transmission cycles. We characterized changes in
      host phenotype in a colonial host-endoparasite system that lacks trophic
      transmission (the freshwater bryozoan Fredericella sultana and myxozoan parasite
      Tetracapsuloides bryosalmonae). We show that parasitism exerts opposing
      phenotypic effects at the colony and module levels. Thus, overt infection (the
      development of infectious spores in the host body cavity) was linked to a
      reduction in colony size and growth rate, while colony modules exhibited a form
      of gigantism. Larger modules may support larger parasite sacs and increase
      metabolite availability to the parasite. Host metabolic rates were lower in
      overtly infected relative to uninfected hosts that were not investing in
      propagule production. This suggests a role for direct resource competition and
      active parasite manipulation (castration) in driving the expression of the
      infected phenotype. The malformed offspring (statoblasts) of infected colonies
      had greatly reduced hatching success. Coupled with the severe reduction in
      statoblast production this suggests that vertical transmission is rare in overtly
      infected modules. We show that although the parasite can occasionally infect
      statoblasts during overt infections, no infections were detected in the surviving
      mature offspring, suggesting that during overt infections, horizontal
      transmission incurs a trade-off with vertical transmission.

PMID- 23965821
TI  - Predicting the risk of an endemic focus of Leishmania tropica becoming
      established in South-Western Europe through the presence of its main vector,
      Phlebotomus sergenti Parrot, 1917.
AB  - The aim of the study was the construction of risk maps for exposure to
      Phlebotomus sergenti, the main vector of Leishmania tropica, with a view to
      identifying hot spots for the potential establishment of this parasite in the
      southwest of Europe. Data were collected on the presence/absence of this vector
      and the ecological and climatic characteristics of 662 sampling sites located in
      the southeast, centre and northeast of the Iberian Peninsula (south-western
      Europe). The environmental factors associated with the distribution of P.
      sergenti were determined. The best predictors for the presence of this dipteran
      were 'altitude', 'land use', 'land surface temperature', 'aspect', 'adjacent land
      cover', 'absence of vegetation in wall' and the 'absence of PVC pipes in the
      drainage holes of retaining walls'. Risk maps for exposure to the vector were
      drawn up based on these variables. The validation of the predictive risk model
      confirmed its usefulness in the detection of areas with a high risk of P.
      sergenti being present. These locations represent potential hot spots for an
      autochthonous focus of L. tropica becoming established. The risk maps produced
      for P. sergenti presence revealed several areas in the centre and south of the
      Iberian Peninsula to be the most prone to this process, which would make it
      possible for the disease to enter south-western Europe.

PMID- 23965819
TI  - Trichuris muris research revisited: a journey through time.
AB  - The mouse whipworm Trichuris muris has long been used as a tractable model of
      human Trichuriasis. Here we look back at the history of T. muris research; from
      the definition of the species and determination of its life cycle, through to the
      complex immune responses that we study today. We highlight the key research
      papers that have developed our understanding of immune responses to this
      parasite, and reflect on how original concepts have been transformed, as our
      knowledge of immunology has grown. Although we have a good understanding of host
      parasite interactions in the context of the underlying cellular immunology, there
      are still many aspects of the biology of the Trichuris parasite that remain
      undefined. We predict that advances in parasite biology will be key in the future
      development of new and improved treatments for Trichuriasis.

PMID- 23965822
TI  - Acriflavine treatment promotes dyskinetoplasty in Trypanosoma cruzi as revealed
      by ultrastructural analysis.
AB  - Trypanosomatid mitochondrial DNA is structured as a giant network of thousands of
      interlocked DNA molecules enclosed within the kinetoplast. The structure and
      replication mechanism of kinetoplast DNA (kDNA) is unique, thereby making it an
      excellent chemotherapeutic target. Alteration in the structural organization of
      kDNA can give rise to dyskinetoplastic (Dk) strains. In Dk cells, the kDNA is
      dispersed in clumps throughout the mitochondrial matrix and not organized into a
      network. In this work, Trypanosoma cruzi epimastigotes were treated with
      acriflavine, a DNA intercalating drug, which promoted a decrease in cell
      proliferation and induced the appearance of Dk protozoa. In treated cells, the
      kinetoplast lost its normal disc-shaped structure because the fibrillar
      arrangement was reduced to a compact, amorphous mass within the mitochondrion.
      Moreover, basic proteins associated with kDNA were redistributed throughout the
      Dk protozoal kinetoplast. We sought to understand how the disruption of the kDNA
      leads to the emergence of the Dk phenotype with atomic force microscopy (AFM)
      analysis of isolated networks. Our results demonstrate that the detachment of
      minicircles from the kDNA disk promotes the disassembly of the network, thereby
      generating Dk cells. Our data strongly suggest that acriflavine inhibits T. cruzi
      multiplication by interfering with kDNA replication.

PMID- 23965823
TI  - Trypanosoma evansi infection impairs memory, increases anxiety behaviour and
      alters neurochemical parameters in rats.
AB  - The aim of this study was to investigate neurochemical and enzymatic changes in
      rats infected with Trypanosoma evansi, and their interference in the cognitive
      parameters. Behavioural assessment (assessment of cognitive performance),
      evaluation of cerebral L-[3H]glutamate uptake, acetylcholinesterase (AChE)
      activity and Ca+2 and Na+, K+-ATPase activity were evaluated at 5 and 30 days
      post infection (dpi). This study demonstrates a cognitive impairment in rats
      infected with T. evansi. At 5 dpi memory deficit was demonstrated by an
      inhibitory avoidance test. With the chronicity of the disease (30 dpi) animals
      showed anxiety symptoms. It is possible the inhibition of cerebral Na+, K+-ATPase
      activity, AChE and synaptosomal glutamate uptake are involved in cognitive
      impairment in infected rats by T. evansi. The understanding of cerebral host
      parasite relationship may shed some light on the cryptic symptoms of animals and
      possibly human infection where patients often present with other central nervous
      system (CNS) disorders.

PMID- 23965825
TI  - The feasibility of non-contact ultrasound for medical imaging.
AB  - High intensity focused ultrasound in air may provide a means for medical and
      biological imaging without direct coupling of an ultrasound probe. In this study,
      an approach based on highly focused ultrasound in air is described and the
      feasibility of the technique is assessed. The overall method is based on the
      observations that (1) ultrasound in air has superior focusing ability and
      stronger nonlinear harmonic generation as compared to tissue propagation and (2)
      a tightly focused field directed into tissue causes point-like spreading that may
      be regarded as a source for generalized diffraction tomography. Simulations of a
      spherically-curved transducer are performed, where the transducer's radiation
      pattern is directed from air into tissue. It is predicted that a focal pressure
      of 162 dB (2.5 kPa) is sufficient to direct ultrasound through the body, and
      provide a small but measurable signal (~1 mPa) upon exit. Based on the
      simulations, a 20 cm diameter array consisting of 298 transducers is constructed.
      For this feasibility study, a 40 kHz resonance frequency is selected based on the
      commercial availability of such transducers. The array is used to focus through
      water and acrylic phantoms, and the time history of the exiting signal is
      evaluated. Sufficient data are acquired to demonstrate a low-resolution
      tomographic reconstruction. Finally, to demonstrate the feasibility to record a
      signal in vivo, a 75 mm * 55 mm section of a human hand is imaged in a C-mode
      configuration. 

PMID- 23965826
TI  - Enhanced potassium selectivity in a bioinspired solid nanopore.
AB  - Biological ion channels present unique ionic properties. They can be highly
      permeable to ions, while selecting only one type of ions, without external energy
      supply. An important research field has been developed to transfer these
      properties to solid state nanoporous membranes in order to develop artificial
      biomimetic nanofilters. One of the promising ways to develop biomimetic
      structures is based on the direct insertion of the gramicidin A, i.e. an ionic
      channel, inside a nanopore. Experiments have recently proved the feasibility of
      such a hybrid membrane with very interesting results regarding the ionic
      selectivity. Here, we propose to interpret these experiments using theoretical
      molecular dynamic simulations which allow us to analyze more profoundly the
      structures of the proteins confined inside the nanopore and the relation between
      their conformation and the observed ionic properties. 

PMID- 23965824
TI  - Seroepidemiological survey for canine angiostrongylosis in dogs from Germany and
      the UK using combined detection of Angiostrongylus vasorum antigen and specific
      antibodies.
AB  - Dogs infected with Angiostrongylus vasorum, a potentially lethal parasite
      parasitizing the heart and pulmonary arteries, may present severe respiratory,
      haematological and neurological signs. In this first large-scale
      seroepidemiological survey, 4003 sera originating from Germany and 4030 from the
      UK were tested by an ELISA for the detection of circulating antigen of A.
      vasorum, and by a separate ELISA detecting specific antibodies. In Germany, where
      mainly western federal states were sampled, 0.3% (n = 13, CI: 0.2-0.6%) of dogs
      were positive in both ELISAs, whereas in total 0.5% (n = 20, CI: 0.3-0.8%) were
      antigen-positive and 2.25% (n = 90, CI: 1.8-2.8%) were positive for specific
      antibodies. Regions with antigen- and antibody-positive animals were overlapping.
      In the UK, where mainly the south of the country was sampled, 0.97% (n = 39, CI:
      0.7-1.3%) of dogs were antigen- and antibody positive. In total, 1.32% (n = 53,
      CI: 1.0-1.7%) were antigen-positive, and 3.2% (n = 129, CI: 2.7-3.8%) were
      positive for specific antibodies, again in overlapping regions. These results
      confirm the occurrence of A. vasorum in a random dog population originating from
      large parts of the countries investigated. The use of the tests alone or in
      combination was considered as a function of their sensitivities and
      specificities, in order to guide efficient clinical and epidemiological
      application.

PMID- 23965827
TI  - Occupational highway transportation deaths among workers aged>=55 years--United
      States, 2003-2010.
AB  - Highway transportation incidents are the leading cause of occupational fatalities
      in the United States, with the highest fatality rates occurring among workers
      aged >=65 years. To characterize older workers at highest risk, CDC analyzed data
      from the Census of Fatal Occupational Injuries (CFOI) for the period 2003-2010
      and compared occupational highway transportation deaths among workers aged 55-64
      years and >=65 years with those among workers aged 18-54 years. This report
      describes the results of that analysis, which indicated that workers aged >=65
      years had the highest overall fatality rate (3.1 highway transportation deaths
      per 100,000 full-time-equivalent [FTE] workers per year), more than three times
      that of workers aged 18-54 years (0.9 per 100,000 FTE workers). This pattern held
      across demographic and occupational categories. These results demonstrate the
      need to further implement interventions that consider road safety risks specific
      to older workers. 

PMID- 23965828
TI  - Japanese encephalitis surveillance and immunization--Asia and the Western
      Pacific, 2012.
AB  - Japanese encephalitis (JE) virus is a leading cause of encephalitis in Asia,
      causing an estimated 67,900 JE cases annually. To control JE, the World Health
      Organization (WHO) recommends that JE vaccine be incorporated into immunization
      programs in all areas where JE is a public health problem. For many decades,
      progress mainly occurred in a small number of high-income Asian countries.
      Recently, prospects for control have improved with better disease burden
      awareness as a result of increased JE surveillance and wider availability of
      safe, effective vaccines. This report summarizes the status of JE surveillance
      and immunization programs in 2012 in Asia and the Western Pacific. Data were
      obtained from the WHO/United Nations Children's Fund (UNICEF) Joint Reporting
      Form (JRF), published literature, meeting reports, and websites. In 2012, 18
      (75%) of the 24 countries with areas of JE virus transmission risk conducted at
      least some JE surveillance, and 11 (46%) had a JE immunization program. Further
      progress toward JE control requires increased awareness of disease burden at the
      national and regional levels, availability of WHO-prequalified pediatric JE
      vaccines, and international support for surveillance and vaccine introduction in
      countries with limited resources. 

PMID- 23965829
TI  - Polio field census and vaccination of underserved populations--northern Nigeria,
      2012-2013.
AB  - In 2012, the World Health Assembly declared completion of polio eradication a
      public health emergency. However, wild poliovirus (WPV) transmission remains
      endemic in three countries (Afghanistan, Nigeria, and Pakistan). In Nigeria, the
      National Stop Transmission of Polio (N-STOP) program, under the umbrella of the
      Nigerian Field Epidemiology and Laboratory Training Program (FELTP), has been
      developed to implement innovative strategies that address the remaining polio
      eradication challenges in Nigeria. One N-STOP initiative focuses on locating and
      vaccinating children aged<5 years in remote nomadic, scattered, and border
      populations in northern Nigeria, where low polio vaccination coverage likely
      contributes to ongoing WPV transmission. During August 2012-April 2013, N-STOP
      conducted field outreach activities that enumerated 40,212 remote settlements,
      including 4,613 (11.5%) settlements never visited by vaccination teams during
      previous polio supplemental immunization activities (SIAs). Enumeration resulted
      in documentation of 906,201 children aged<5 years residing in these settlements,
      including 53,738 (5.9%) who had never received polio vaccination, and in
      detection of 211 unreported cases of acute flaccid paralysis (AFP) with onset of
      illness in the 6 months before enumeration. Sustaining access to underserved
      populations in remote settlements in future SIAs will increase overall population
      immunity and should decrease WPV transmission. By providing a flexible and
      capable workforce consisting of Nigerian citizens, N-STOP is able to support
      evaluation and implementation of innovative polio eradication strategies in
      Nigeria while building local public health capacity with a potential to address
      other public health problems following the eradication of polio from Nigeria.

PMID- 23965830
TI  - Investigational drug available directly from CDC for the treatment of infections
      with free-living amebae.
AB  - Infections caused by free-living amebae (FLA) are severe and life-threatening.
      These infections include primary amebic meningoencephalitis (PAM) caused by
      Naegleria fowleri and granulomatous amebic encephalitis caused by Balamuthia
      mandrillaris and Acanthamoeba species. Although several drugs have in vitro
      activity against FLA, mortality from these infections remains>90% despite
      treatment with combinations of drugs.

PMID- 23965831
TI  - Notes from the field: eye injuries sustained at a foam party--Collier County,
      Florida 2012.
AB  - On May 26, 2012, the Collier County Health Department was notified by law
      enforcement and hospital personnel that approximately 40 persons had sought care
      at local emergency departments because of severe eye irritation and pain.
      Patients reported that they had attended a foam party at a local nightclub the
      night before. Syndromic surveillance activities carried out by the Florida
      Department of Health identified 35 patients who had visited an emergency
      department in Collier County on May 26 with a chief complaint related to eye
      injuries, well above the expected number of less than 10. 

PMID- 23965833
TI  - Patient safety in interventional radiological procedures: safety checklists and
      protocols.

PMID- 23965832
TI  - A hidden role of the inactivated FANCD2: upregulating DeltaNp63.
AB  - A compromised Fanconi Anemia (FA) signaling pathway, often resulting from an
      inactivated FANCD2, was recently recognized to contribute to the development of
      non-FA human tumors. However, it is largely unknown as to how an impaired FA
      pathway or an inactivated FANCD2 promotes tumorigenesis. Here we unexpectedly
      found that DeltaNp63 mRNA was expressed at high levels in human cancer cells
      carrying an impaired FA pathway compared to the corresponding control cells
      carrying an intact FA pathway. This observation was recapitulated upon
      conditionally managing the status of FANCD2 monoubiquitination /activation in
      293T cells. Importantly, DeltaNp63 elevation upon FANCD2 inactivation was
      confirmed in human fibroblasts derived from FA patients. Moreover, we have
      identified a 189 bp DNA fragment downstream of the DeltaNp63 promoter (P2) that
      can mediate the upregulation of DeltaNp63 by an inactivated FANCD2, and
      determined that elevated DeltaNp63 is high enough to promote cancer cell
      proliferation and metastasis. In vivo, the elevation of FAVL, a tumor promotion
      factor that inhibits FANCD2 activation, was found to be positively associated
      with DeltaNp63 expression in human cancer tissues. Collectively, these results
      document a novel role of an inactivated FANCD2 in upregulating DeltaNp63,
      advancing our understanding of how an impaired FA pathway contributes to the
      pathogenesis of human cancer. 

PMID- 23965834
TI  - Associations between communication climate and the frequency of medical error
      reporting among pharmacists within an inpatient setting.
AB  - OBJECTIVE: Although error-reporting systems enable hospitals to accurately track
      safety climate through the identification of adverse events, these systems may be
      underused within a work climate of poor communication. The objective of this
      analysis is to identify the extent to which perceived communication climate among
      hospital pharmacists impacts medical error reporting rates. METHODS: This cross
      sectional study used survey responses from more than 5000 pharmacists responding
      to the 2010 Hospital Survey on Patient Safety Culture (HSOPSC). Two composite
      scores were constructed for "communication openness" and "feedback and about
      error," respectively. Error reporting frequency was defined from the survey
      question, "In the past 12 months, how many event reports have you filled out and
      submitted?" Multivariable logistic regressions were used to estimate the
      likelihood of medical error reporting conditional upon communication openness or
      feedback levels, controlling for pharmacist years of experience, hospital
      geographic region, and ownership status. RESULTS: Pharmacists with higher
      communication openness scores compared with lower scores were 40% more likely to
      have filed or submitted a medical error report in the past 12 months (OR, 1.4;
      95% CI, 1.1-1.7; P = 0.004). In contrast, pharmacists with higher communication
      feedback scores were not any more likely than those with lower scores to have
      filed or submitted a medical report in the past 12 months (OR, 1.0; 95% CI, 0.8
      1.3; P = 0.97). CONCLUSIONS: Hospital work climates that encourage pharmacists to
      freely communicate about problems related to patient safety is conducive to
      medical error reporting. The presence of feedback infrastructures about error may
      not be sufficient to induce error-reporting behavior.

PMID- 23965835
TI  - Application of an engineering problem-solving methodology to address persistent
      problems in patient safety: a case study on retained surgical sponges after
      surgery.
AB  - Despite innumerable attempts to eliminate the postoperative retention of surgical
      sponges, the medical error persists in operating rooms worldwide and places
      significant burden on patient safety, quality of care, financial resources, and
      hospital/physician reputation. The failure of countless solutions, from new
      sponge counting methods to radio labeled sponges, to truly eliminate the event in
      the operating room requires that the emerging field of health-care delivery
      science find innovative ways to approach the problem. Accordingly, the VA
      National Center for Patient Safety formed a unique collaboration with a team at
      the Thayer School of Engineering at Dartmouth College to evaluate the retention
      of surgical sponges after surgery and find a solution. The team used an
      engineering problem solving methodology to develop the best solution. To make the
      operating room a safe environment for patients, the team identified a need to
      make the sponge itself safe for use as opposed to resolving the relatively
      innocuous counting methods. In evaluation of this case study, the need for
      systematic engineering evaluation to resolve problems in health-care delivery
      becomes clear.

PMID- 23965836
TI  - Exploring physician hand hygiene practices and perceptions in 2 community-based
      Canadian hospitals.
AB  - OBJECTIVE: The purpose of this study was to explore the self-reported hand
      hygiene practices and the predictors of hand hygiene among physicians in a
      midsize Canadian city. METHODS: A descriptive cross-sectional survey using self
      report questionnaire administered to a complete list of 354 local physicians.
      Perception of proper compliance was defined in a participant if he/she indicated
      performance of hand hygiene before and after every patient contact at least 80%
      of the time. RESULTS: One hundred fifty-four physicians completed the
      questionnaire, yielding a 44.9% response rate. Only 45.3% of our sample reported
      performing preprocedure and postprocedure hand hygiene at least 80% of the time.
      Stepwise logistic regression results suggested that the variables "presence of
      hand hygiene auditing" (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.47
      6.91), "being too busy" (OR, 0.43; 95% CI, 0.20-0.90), "forgetfulness" (OR, 0.27;
      95%, CI, 0.13-0.56), and "the perception that hand hygiene products are damaging
      to the skin" (OR, 0.31;95% CI, 0.11-0.88) were the only independent predictors of
      physician hand hygiene compliance. CONCLUSIONS: Hand hygiene compliance among
      physicians remains an issue. The findings emphasize the need of health-care
      institutions to prioritize hand hygiene by ensuring proper promotion and
      enforcement of current policies to all practicing HCPs.

PMID- 23965837
TI  - What happens to the medication regimens of older adults during and after an acute
      hospitalization?
AB  - BACKGROUND: Hospitalized elderly patients are at risk for medication errors and
      nonadherence when discharged home. OBJECTIVE: To describe how older patients'
      medications change during and after hospitalizations and what patients ultimately
      take after discharge. METHODS: We conducted an observational cohort study of 95
      patients aged 65 years and older admitted to Johns Hopkins Bayview Medical Center
      in 2007. Inclusion criteria included admissions longer than 24 hours and
      discharge to home. Medication lists from three periods were recorded:
      prehospitalization, day of discharge, and 3 days after discharge. In comparing
      lists, we characterized: new and discontinued medications, changes in dosage, and
      changes in frequency. RESULTS: Before admission, patients were taking a total of
      701 medications (mean, 7 per patient). Upon discharge, 192 new medicines were
      started (2.0 per patient), 76 discontinued (0.8 per patient), 67 changed in
      frequency, (0.7 per patient), and 45 changed in dosage (0.5 per patient).
      Antibiotics and antihypertensives were the most commonly prescribed new
      medications. Antihypertensives were also most likely to be discontinued. At day 3
      after discharge, patients were adherent with 98% (763/778) of medications.
      However, 25% of antihypertensives and 88% analgesics discontinued by hospitalists
      on the day of discharge were reinitiated by patients upon their return home.
      CONCLUSIONS: During hospitalizations, medications of older adults change
      substantially. Despite clear medication reconciliation efforts in the hospital
      environment, medication errors occur upon discharge to home. Because current
      standards are yielding suboptimal results, alternate methodologies for promoting
      medication adherence should also be considered, developed, and studied for
      effectiveness.

PMID- 23965838
TI  - Improving patient safety in the ICU by prospective identification of missing
      safety barriers using the bow-tie prospective risk analysis model.
AB  - OBJECTIVES: To improve patient safety, potential critical events should be
      analyzed for the existence of preventive barriers. The aim of this study was to
      prospectively identify existing and missing barriers using the Bow-Tie model. We
      expected that the analysis of these barriers would lead to feasible
      recommendations to improve safety in daily patient care. METHODS:
      Multidisciplinary teams of doctors and nurses on a 28 bed ICU conducted the
      study. The Bow-Tie analysis was performed on intrahospital transportation,
      unplanned extubation, and communication, which led to 9 critical events. For each
      event, potential threats and consequences were defined and placed in a Bow-Tie
      diagram. Then, barriers were determined, ways to prevent the threat or limit the
      consequences. The barriers were defined as existing or missing and analyzed for
      feasibility. RESULTS: Intrahospital transportation: this hazard led to 7 critical
      events, the Bow-Tie analysis to 52 missing but implementable barriers and 8
      practical recommendations. For example, a pretransportation checklist.Unplanned
      extubation: this Bow-Tie analysis revealed 15 implementable missing barriers (of
      a total of 32) and led to 22 recommendations. One of them was optimizing
      treatment of delirium.Communication: this analysis showed 21 barriers, of which,
      12 were missing but feasible to implement. These barriers led to 7
      recommendations such as the need to cosign after the handover of a patient.
      CONCLUSIONS: Prospective risk analysis using the Bow-Tie model proved usable to
      identify existing and missing barriers for potential critical events. Many
      missing barriers seemed feasible to implement and led to practical
      recommendations and improvements in patient safety.

PMID- 23965839
TI  - Medication reconciliation: comparing a customized medication history form to a
      standard medication form in a specialty clinic (CAMPII 2).
AB  - BACKGROUND: Medication history forms completed by patients are an essential part
      of the medication reconciliation process. OBJECTIVE: In a crossover prospective
      study, investigators compared the accuracy and acceptability of a "fill-in-the
      blank" medication history form (USUAL) to a customized form (CUSTOM) that
      contained a checklist of the 44 most frequently prescribed diabetes clinic
      medications. METHODS: The content of both forms was compared to a "gold-standard"
      medication list compiled by a clinical pharmacist who conducted a medication
      history and reviewed pharmacy profiles and medical chart. Subject preference and
      time to complete the forms were also determined. Accurate was defined as complete
      and correct (name, dose, and frequency) relative to the gold standard. RESULTS: A
      total of 77 subjects completed both forms. Complete list accuracy was poor; there
      was no difference in the accuracy between CUSTOM (6.5%) and USUAL (9.1%) (odds
      ratio [OR], 0.33; P = 0.62). Out of a total of 648 medications, subjects
      accurately listed 43.7% of medications on CUSTOM and 45.5% on USUAL (OR, 0.88; P
      = 0.41). The 44 medications on the checklist were more than twice as likely to be
      accurately reported using CUSTOM than with USUAL (OR, 2.1; P = 0.0002). More
      subjects preferred CUSTOM (65.7%) compared with USUAL (32.8%, P = 0.007).
      CONCLUSION: Medication self-report is very poor, and few subjects created an
      accurate list on either form. Subjects were more likely to report the drugs on
      the checklist using CUSTOM than when they used USUAL; however, there was no
      difference in the overall accuracy between CUSTOM and USUAL.

PMID- 23965840
TI  - Using a patient internet portal to prevent adverse drug events: a randomized,
      controlled trial.
AB  - OBJECTIVES: Adverse drug events (ADEs) are common in ambulatory care and may
      result from poor patient-physician communication about medication-related
      symptoms. A module was developed within an electronic patient portal that was
      designed to enhance communication about medication symptoms and, in turn, reduce
      ADEs and health-care utilization. METHODS: The researchers conducted a
      randomized, controlled clinical trial of MedCheck, an automated electronic
      message generated in a patient Internet portal. MedCheck asked intervention
      patients if they had filled a recent prescription and if they had experienced any
      problems with the medication. Patients' responses were forwarded automatically to
      primary care physicians. The study enrolled 375 intervention patients and 363
      controls. After 3 months, the investigators reviewed patients' medical records
      and conducted telephone interviews to identify ADEs and to assess health-care
      utilization. RESULTS: Among the 375 intervention patients, 184 (49%) responded to
      at least 1 MedCheck message. Patients reported 52 unfilled prescriptions and 56
      medication problems. Patients responded to 72% of messages within 1 day. There
      was no statistically significant difference between intervention and control
      groups in the rate of ADEs, preventable or ameliorable ADEs, serious ADEs, or in
      subjects' health-care utilization. CONCLUSIONS: Internet portals have the
      potential to enhance patient-physician communication. However, additional
      development is required to demonstrate that such interventions can improve
      medication safety or health-care utilization.

PMID- 23965841
TI  - Effects of energy deficit, dietary protein, and feeding on intracellular
      regulators of skeletal muscle proteolysis.
AB  - This study was undertaken to characterize the ubiquitin proteasome system (UPS)
      response to varied dietary protein intake, energy deficit (ED), and consumption
      of a mixed meal. A randomized, controlled trial of 39 adults consuming protein at
      0.8 (recommended dietary allowance [RDA]), 1.6 (2*-RDA), or 2.4 (3*-RDA) g . kg(
      1) . d(-1) for 31 d. A 10-d weight maintenance (WM) period was followed by 21 d
      of 40% ED. Ubiquitin (Ub)-mediated proteolysis and associated gene expression
      were assessed in the postabsorptive (fasted) and postprandial (fed; 480 kcal, 20
      g protein) states after WM and ED by using muscle biopsies, fluorescence-based
      assays, immunoblot analysis, and real-time qRT-PCR. In the assessment of UPS
      responses to varied protein intakes, ED, and feeding, the RDA, WM, and fasted
      measures served as appropriate controls. ED resulted in the up-regulation of UPS
      associated gene expression, as mRNA expression of the atrogenes muscle RING
      finger-1 (MuRF1) and atrogin-1 were 1.2- and 1.3-fold higher (P<0.05) for ED than
      for WM. However, mixed-meal consumption attenuated UPS-mediated proteolysis,
      independent of energy status or dietary protein, as the activities of the 26S
      proteasome subunits beta1, beta2, and beta5 were lower (P<0.05) for fed than for
      fasted. Muscle protein ubiquitylation was also 45% lower (P<0.05) for fed than
      for fasted, regardless of dietary protein and energy manipulations. Independent
      of habitual protein intake and despite increased MuRF1 and atrogin-1 mRNA
      expression during ED, consuming a protein-containing mixed meal attenuates Ub
      mediated proteolysis.

PMID- 23965842
TI  - Functional responses and molecular mechanisms involved in histone-mediated
      platelet activation.
AB  - Histones are highly alkaline proteins found in cell nuclei and they can be
      released by either dying or inflammatory cells. The recent observations that
      histones are major components of neutrophil extracellular traps and promote
      platelet aggregation and platelet-dependent thrombin generation have shown that
      these proteins are potent prothrombotic molecules. Because the mechanism(s) of
      platelet activation by histones are not completely understood, we explored the
      ability of individual recombinant human histones H1, H2A, H2B, H3 and H4 to
      induce platelet activation as well as the possible molecular mechanisms involved.
      All histones were substrates for platelet adhesion and spreading and triggered
      fibrinogen binding, aggregation, von Willebrand factor release, P-selectin and
      phosphatidylserine (PS) exposure and the formation of platelet-leukocyte
      aggregates; however, H4 was the most potent. Histone-mediated fibrinogen binding,
      P-selectin and PS exposure and the formation of mixed aggregates were potentiated
      by thrombin. Histones induced the activation of ERK, Akt, p38 and NFkappaB.
      Accordingly, histone-induced platelet activation was significantly impaired by
      pretreatment of platelets with inhibitors of ERK (U 0126), PI3K/Akt (Ly 294002),
      p38 (SB 203580) and NFkappaB (BAY 11-7082 and Ro 106-9920). Preincubation of
      platelets with either aspirin or dexamethasone markedly decreased fibrinogen
      binding and the adhesion mediated by histones without affecting P-selectin
      exposure. Functional platelet responses induced by H3 and H4, but not H1, H2A and
      H2B, were partially mediated through interaction with Toll-like receptors -2 and 
      4. Our data identify histones as important triggers of haemostatic and
      proinflammatory platelet responses, and only haemostatic responses are partially
      inhibited by anti-inflammatory drugs. 

PMID- 23965843
TI  - Response to 'Abatacept in relapsing polychondritis' by Moulis et al.

PMID- 23965845
TI  - Use of staged molecular analysis to determine causes of unexplained central
      nervous system infections.
AB  - No agent is implicated in most central nervous system (CNS) infections. To
      investigate cerebrospinal fluid samples from patients with CNS infections of
      unknown cause in 1 hospital in Taiwan, we used a staged molecular approach,
      incorporating techniques including multiplex MassTag PCR, 16S rRNA PCR, DNA
      microarray, and high-throughput pyrosequencing. We determined the infectious
      agent for 31 (24%) of 131 previously negative samples. Candidate pathogens were
      identified for 25 (27%) of 94 unexplained meningitis cases and 6 (16%) of 37
      unexplained encephalitis cases. Epstein-Barr virus (18 infections) accounted for
      most of the identified agents in unexplained meningitis cases, followed by
      Escherichia coli (5), enterovirus (2), human herpesvirus 2 (1), and Mycobacterium
      tuberculosis. Herpesviruses were identified in samples from patients with
      unexplained encephalitis cases, including varicella-zoster virus (3 infections),
      human herpesvirus 1 (2), and cytomegalovirus (1). Our study confirms the power of
      multiplex MassTag PCR as a rapid diagnostic tool for identifying pathogens
      causing unexplained CNS infections. 

PMID- 23965846
TI  - LaAlO3 stoichiometry is key to electron liquid formation at LaAlO3/SrTiO3
      interfaces.
AB  - Emergent phenomena, including superconductivity and magnetism, found in the two
      dimensional electron liquid (2-DEL) at the interface between the insulators
      lanthanum aluminate (LaAlO3) and strontium titanate (SrTiO3) distinguish this
      rich system from conventional 2D electron gases at compound semiconductor
      interfaces. The origin of this 2-DEL, however, is highly debated, with focus on
      the role of defects in the SrTiO3, while the LaAlO3 has been assumed perfect.
      Here we demonstrate, through experiments and first-principle calculations, that
      the cation stoichiometry of the nominal LaAlO3 layer is key to 2-DEL formation:
      only Al-rich LaAlO3 results in a 2-DEL. Although extrinsic defects, including
      oxygen deficiency, are known to render LaAlO3/SrTiO3 samples conducting, our
      results show that in the absence of such extrinsic defects an interface 2-DEL can
      form. Its origin is consistent with an intrinsic electronic reconstruction
      occurring to counteract a polarization catastrophe. This work provides insight
      for identifying other interfaces where emergent behaviours await discovery. 

PMID- 23965844
TI  - The phenotype of TNF receptor-associated autoinflammatory syndrome (TRAPS) at
      presentation: a series of 158 cases from the Eurofever/EUROTRAPS international
      registry.
AB  - OBJECTIVE: To evaluate the genetic findings, demographic features and clinical
      presentation of tumour necrosis factor receptor-associated autoinflammatory
      syndrome (TRAPS) in patients from the Eurofever/EUROTRAPS international registry.
      METHODS: A web-based registry collected retrospective data on patients with
      TNFRSF1A sequence variants and inflammatory symptoms. Participating hospitals
      included paediatric rheumatology centres and adult centres with a specific
      interest in autoinflammatory diseases. Cases were independently validated by
      experts in the disease. RESULTS: Complete information on 158 validated patients
      was available. The most common TNFRSF1A variant was R92Q (34% of cases), followed
      by T50M (10%). Cysteine residues were disrupted in 27% of cases, accounting for
      39% of sequence variants. A family history was present in 19% of patients with
      R92Q and 64% of those with other variants. The median age at which symptoms began
      was 4.3 years but 9.1% of patients presented after 30 years of age. Attacks were
      recurrent in 88% and the commonest features associated with the pathogenic
      variants were fever (88%), limb pain (85%), abdominal pain (74%), rash (63%) and
      eye manifestations (45%). Disease associated with R92Q presented slightly later
      at a median of 5.7 years with significantly less rash or eye signs and more
      headaches. Children were more likely than adults to present with lymphadenopathy,
      periorbital oedema and abdominal pains. AA amyloidosis has developed in 16 (10%)
      patients at a median age of 43 years. CONCLUSIONS: In this, the largest reported
      case series to date, the genetic heterogeneity of TRAPS is accompanied by a
      variable phenotype at presentation. Patients had a median 70 symptomatic days a
      year, with fever, limb and abdominal pain and rash the commonest symptoms.
      Overall, there is little evidence of a significant effect of age or genotype on
      disease features at presentation.

PMID- 23965847
TI  - Effect of supplemental vitamin E on antibody titer in Japanese black calves
      vaccinated against bovine herpesvirus-1.
AB  - We investigated the effect of supplemental vitamin E on antibody titer against
      bovine herpesvirus-1 (BHV-1) in Japanese Black calves after vaccination with
      modified live virus. Thirty calves kept at the same farm were studied. They were
      divided into two groups; fifteen calves received 300 IU/day of vitamin E orally
      from 1 to 3 months of age (VE Group), and the other fifteen calves did not
      receive vitamin E supplement (Control Group). BHV-1 modified live vaccine was
      injected twice to all calves when they were 2 and 3 months of age. Following the
      vaccination, serum vitamin E concentration and neutralizing antibody titer to BHV
      1 were measured over time. VE Group showed higher serum vitamin E at 2, 3 and 4
      months of age compared to Control Group (P<0.05). The antibody titer in Control
      Group was the highest at 1 month of age, and it gradually decreased until 4
      months of age. VE Group showed increase in antibody titer at 4 months of age
      resulting in significant difference (P<0.01) from Control Group. This study
      demonstrated that vitamin E supplementation to Japanese Black calves could
      increase antibody production after the second modified live BHV-1 vaccination. 

PMID- 23965848
TI  - Maternally and naturally acquired antibody to Mannheimia haemolytica in Japanese
      Black calves.
AB  - We investigated the dynamics and duration of antibody titer against Mannheimia
      haemolytica in Japanese Black calves. Twenty unvaccinated calves from two
      Japanese Black breeding farms in Kagoshima Prefecture, Japan, were studied. The
      antibody titer against M. haemolytica reached the lowest level at 8 weeks of age
      after birth. Calves began producing antibody against M. haemolytica by themselves
      between 8 and 12 weeks of age. The results of this study might help designing a
      vaccination program against M. haemolytica for Japanese Black calves. 

PMID- 23965849
TI  - Establishment and application of a loop-mediated isothermal amplification method
      for simple, specific, sensitive and rapid detection of Toxoplasma gondii.
AB  - The Loop-mediated isothermal amplification (LAMP) method amplifies DNA with high
      simply, specificity, sensitivity and rapidity. In this study, A LAMP assay with 6
      primers targeting a highly conserved region of the GRA1 gene was developed to
      diagnose Toxoplasma gondii. The reaction time of the LAMP assay was shortened to
      30 min after optimizing the reaction system. The LAMP assay was found to be
      highly specific and stable. The detection limit of the LAMP assay was 10 copies,
      the same as that of the conventional PCR. We used the LAMP assay to develop a
      real-time fluorogenic protocol to quantitate T. gondii DNA and generated a log
      linear regression plot by plotting the time-to-threshold values against genomic
      equivalent copies. Furthermore, the LAMP assay was applied to detect T. gondii
      DNA in 423 blood samples and 380 lymph node samples from 10 pig farms, and
      positive results were obtained for 7.8% and 8.2% of samples, respectively. The
      results showed that the LAMP method is slightly more sensitive than conventional
      PCR (6.1% and 7.6%). Positive samples obtained from 6 pig farms. The LAMP assay
      established in this study resulted in simple, specific, sensitive and rapid
      detection of T. gondii DNA and is expected to play an important role in clinical
      detection of T. gondii. 

PMID- 23965850
TI  - The effect of L-carnitine on oxidative stress responses of experimental contrast
      induced nephropathy in rats.
AB  - This study was conducted to investigate the prophylactic effects of carnitine
      against contrast-induced nephropathy (CIN) and its relation to
      oxidant/antioxidant status in kidney, liver, heart, spleen and lung tissues in a
      CIN rat model. Twenty-eight adult male Wistar rats were divided into 4 groups,
      the control, contrast media (CM), carnitine and contrast media+carnitine
      (CM+carnitine) groups. Animals were placed in individual metabolism cages, and on
      the 2nd day, rats were deprived of water for 24 hr. On the 3rd day, contrast
      media were administered to groups CM and CM+carnitine. L-carnitine was
      administered on days 2, 3 and 4. Histopathological changes were evaluated in the
      right kidney after euthanization. Superoxide dismutase (SOD) and catalase (CAT)
      activities and glutathione (GSH) and malondialdehyde (MDA) levels were measured
      in renal, liver, heart, spleen and lung tissues. The SOD activities in the renal
      (P<0.05), liver (P<0.001) and spleen (P<0.05) tissues were increased in the
      carnitine group. The CAT activities in the spleen tissue were decreased (P<0.01)
      only in the CM group. Renal (P<0.05), liver (P<0.001), spleen (P<0.001) and lung
      tissue (P<0.01) GSH levels were found to be higher in the carnitine group. In
      renal, liver and lung tissues, the MDA levels increased in the CM group
      (P<0.001). The histopathological findings showed that L-carnitine may have a
      preventative effect in alleviating the negative effects of CIN. Similar to this,
      L-carnitine may play a major role in the stability of the antioxidant status in
      the kidney, liver, spleen and lung of the CIN rat model. 

PMID- 23965852
TI  - [Cellular pathology of neurodegenerative disorders].
AB  - Common cellular and molecular mechanisms including protein aggregation and
      inclusion body formation are involved in many neurodegenerative diseases. alpha
      Synuclein is a major component of Lewy bodies in Parkinson's disease (PD) as well
      as in glial cytoplasmic inclusions in multiple system atrophy (MSA). Tau is a
      principal component of neurofibrillary and glial tangles in tauopathies.
      Recently, TDP-43 was identified as a component of ubiquitinated inclusions in
      amyotrophic lateral sclerosis and frontotemporal lobar degeneration. PD is
      traditionally considered a movement disorder with hallmark lesions in the
      brainstem pigmented nuclei. However, pathological changes occur in widespread
      regions of the central and peripheral nervous systems in this disease.
      Furthermore, primary glial involvement ("gliodegeneration") can be observed in PD
      and MSA as well as in tauopathy. The present article reviews abnormal protein
      accumulation and inclusion body formation inside and outside the central nervous
      system. 

PMID- 23965851
TI  - The anti-malarial chloroquine overcomes primary resistance and restores
      sensitivity to trastuzumab in HER2-positive breast cancer.
AB  - Autophagy may control the de novo refractoriness of HER2 gene-amplified breast
      carcinomas to the monoclonal antibody trastuzumab (Herceptin). Tumor cells
      originally obtained from a patient who rapidly progressed on trastuzumab ab
      initio display increased cellular levels of the LC3-II protein--a finding that
      correlates with increased numbers of autophagosomes--and decreased levels of the
      autophagy receptor p62/SQSTM1, a protein selectively degraded by autophagy.
      Trastuzumab-refractory cells are in a state of "autophagy addiction" because
      genetic ablation of autophagy-specific genes (ATG8, ATG5, ATG12) notably reduces
      intrinsic refractoriness to trastuzumab. When the anti-malarial lysosomotropic
      drug chloroquine impedes autophagic resolution of the accumulation of
      autophagolysosomes formed in the presence of trastuzumab, cells commit to die by
      apoptosis. Accordingly, combination treatment with trastuzumab and chloroquine
      radically suppresses tumor growth by > 90% in a tumor xenograft completely
      refractory to trastuzumab. Adding chloroquine to trastuzumab-based regimens may
      therefore improve outcomes among women with autophagy-addicted HER2-positive
      breast cancer.

PMID- 23965853
TI  - [Reversible cerebral vasoconstriction syndrome with cortical subarachnoid
      hemorrhage presenting as thunderclap headache-a long followed up case].
AB  - A 59-year-old woman presented with thunderclap headache. Cranial CT showed
      cortical subarachnoid hemorrhage (cSAH) at the right parietal lobe and cerebral
      angiography on day 5 revealed multiple cerebral arterial constriction, diagnosed
      as reversible cerebral vasoconstriction syndrome (RCVS). We could not detect
      vasoconstriction in MRA at the first examination on day 4, and vasoconstrictive
      finding appeared around Willis circle 8 days later. There was a temporal
      difference in a cephalalgic symptom and vasoconstrictive appearance. Clinical
      symptoms completely recovered and head CT, MRI/MRA findings were reversible after
      two months, reflecting a rather good RCVS outcome. However, we also followed up
      this case precisely using single photon emission computed tomography (SPECT) with
      easy Z-score imaging system (e-ZIS), and hypoperfusion at the locus of cSAH
      persisted for more than one year. This finding strongly suggests that tissue
      damage in the cSAH locus induced by RCVS may be subclinicaly irreversible, even
      though clinical symptoms and abnormalities in cranial MRI and MRA completely
      recover.SPECT may be a high sensitive technique to detect the irreversible lesion
      in RCVS. 

PMID- 23965854
TI  - [A case of hypomyelinating leukodystrophy with new homozygous mutation in
      POLR3A].
AB  - We describe a 34-year-old man with hypomyelination, hypogonadotropic
      hypogonadism, ataxia, and myopia without hypodontia. He was born to non
      consanguineous parents, and had an elder brother who showed a similar phenotype.
      Laboratory studies demonstrated low level of LH, FSH and testosterone. MRI showed
      hypomyelination, atrophy of the cerebellum and the hypoplastic corpus callosum.
      Homozygous missensze mutation c.2350G>A (p.Gly784Ser) was found in POLR3A,which
      codes for the largest subunit of RNA polymerase III. Since PolIII-related
      leukodystrophies shows various combination of neurologic and non-neurologic
      features, additional reports will help to confirm the mechanism of this disease. 

PMID- 23965855
TI  - [Acute oropharyngeal palsy with localized sensory impairment resembling symptom
      distribution of acute pharyngeal-cervical-brachial variant in a patient with
      Guillain-Barre syndrome].
AB  - We present the case of a 40-year-old woman who experienced dysarthria and,
      numbness in her upper extremities and posterior region of her neck. Upon
      admission to our hospital, neurological examination revealed rhinolalia aperta
      and an incomplete palatoplegia; however, muscle strength in the neck and limbs
      was satisfactorily preserved, tendon reflexes were normal, and pathological
      reflexes were not observed. Cerebrospinal fluid and electrophysiological test
      results were also normal. On day 3 of hospitalization, a slight backflow of fluid
      into the nasal cavity was observed upon deglutition, and vibration perception was
      also impaired in the bilateral arms. Her serum tested positive for immunoglobulin
      G antibodies against such gangliosides as GT1a, GQ1b, GT1b, and GD1a. Despite
      normal tendon reflexes, she was diagnosed with a subtype of Guillain-Barre
      syndrome (GBS), and was treated with intravenous immunoglobulin therapy.
      Subsequently, her symptoms improved. Due to the combination of oropharyngeal
      palsy and sensory impairment, it was more likely the GBS subtype in this patient
      was acute oropharyngeal palsy (AOP) rather than pharyngeal-cervical-brachial
      (PCB) variant; though interestingly, the patient's sensory disturbance was
      limited to the posterior neck and upper extremities, which resembles the
      distribution of motor symptoms in PCB variant. The present case was a rare and
      important phenotype, demonstrating diversities of GBS variants. We also believe
      that GBS subtypes may represent a continuum of pathological conditions and not
      just one static condition. However, further studies involving serological
      characteristics of anti-ganglioside antibodies and clinical features for GBS are
      needed to clarify this possibility. 

PMID- 23965856
TI  - [A case of systemic lupus erythematosus predominantly presenting with myositis at
      onset].
AB  - A 42-year-old woman presented with rapid myalgia of the thigh and muscle weakness
      in the proximal limbs with markedly elevated serum CK. Despite positive for
      antibodies to anti-nuclear, anti-ds-DNA, anti-ss-DNA, anti-Sm, anti-SS-A/Ro, C
      ANCA, anti-U1-RNP and anti-ribosome and slight lymphocytopenia and
      hypocomplementemia, there was no symptom associated with systemic lupus
      erythematosus (SLE). Proteinuria and hematuria were initially considered to be
      associated with renal damage due to myoglobinuria. Muscle MRI demonstrated high
      signal intensities in the rectus femoris. Muscle biopsy of the rectus femoris
      demonstrated a mild variation in fiber size, a few necrotic and several
      regenerating fibers and minimal lymphocytic infiltration in the endomysium, which
      suggested myopathic changes with mild necrotic and regenerating processes. Thus
      she was diagnosed as idiopathic myositis at first, and was treated by
      corticosteroid therapy. Her myalgia and CK level improved, but the proteinuria
      and hematuria were persistent. A renal biopsy demonstrated lupus nephritis, and
      SLE with myositis was confirmed. She was treated with additional tacrolimus
      administration, and her proteinuria and hematuria also improved. The present case
      suggests that patients who predominantly present with myositis accompanied by
      nephritis and autoantibodies should be considered as SLE with myositis. 

PMID- 23965857
TI  - [A case of migraine with aura attenuated by transcatheter closure of atrial
      septal defect].
AB  - A 38-year old man with an 8-year history of migraine with subclinical abnormal
      brain lesions on MRI was admitted to our hospital. His migraine attacks followed
      visual disturbance or dysarthria. Brain MRI revealed old infarctions restricted
      to the posterior circular region. On transesophageal cardiography, an atrial
      septal defect (ASD) was detected, and a bubble study showed an immediate
      appearance of many bubbles in the left atrium via ASD without Valsalva maneuver.
      The bubble study on transcranial-color-flow imaging also detected micro-embolic
      signals at the left vertebral artery and the left middle cerebral artery without
      Valsalva maneuver. Since paradoxical embolism via ASD was highly suspected and
      Qp/Qs was more than 1.5, transcatheter closure of ASD using AMPLATZER((r)) Septal
      Occluder was performed. At a 2-year follow up, no recurrence of either migraine
      or infarction was found. This case indicates the relevance of right-to-left shunt
      to migraine with aura, as well as the usefulness of transcatheter closure of ASD
      using AMPLATZER((r)) Septal Occluder for treatment of migraine with aura. 

PMID- 23965858
TI  - [Cheyne-Stokes respiration appeared in an early stage of the disease in a patient
      with Creutzfeldt-Jakob disease].
AB  - A 77-year-old female developed vertigo and dysarthria. Two months later, she was
      hospitalized with disorientation and ataxia. CSF showed increased levels of NSE,
      14-3-3 protein and tau. EEG demonstrated periodic synchronous discharges (PSD).
      Brain MRI showed abnormal high intensity areas in the cerebral cortices,
      especially in the occipital lobes, putamen and caudate nucleus bilaterally, on
      DWI. Genetical analysis of prion protein revealed no specific mutation. She was
      diagnosed as having sporadic Creutzfeldt-Jakob disease (CJD). Cheyne-Stokes
      respiration (CSR) had been observed since an early stage, and decreased 5 months
      later coincident with attenuation of myoclonus and PSD. We should also pay
      attention to CSR in the diagnosis of CJD, although the complication is rare. 

PMID- 23965859
TI  - [A case of cerebral cardioembolism successfully treated by Merci retriever
      despite a large ischemic change on diffusion-weighted MR imaging].
AB  - A 63-year-old man with paroxysmal atrial fibrillation presented with aphasia
      (16:30) followed by right hemiplegia. The last known time that he was clinically
      well was 14:30. On admission (17:43), his baseline NIHSS score was 34. Head
      diffusion-weighted MR imaging (DWI) demonstrated large hyperintense signals
      throughout the left middle cerebral artery (MCA) territory. The left carotid
      angiogram (CAG) demonstrated occlusion of the left ICA 2 cm distal from the
      bifurcation. The right CAG showed a small branch laterally extending from the
      left anterior cerebral artery (ACA). Mechanical thrombectomy with a Merci
      retriever removed a large amount of thrombi after the first trial. The left ICA
      and MCA were recanalized to grade TICI 2b. The left hemiplegia was markedly
      improved, and he could walk independently. His NIHSS score was 11 at discharge.
      Revascularization therapy may improve a motor deficit in patients with possible
      penumbra of the precentral gyrus by collateral circulation from the ACA even if
      the ischemic lesion in the MCA territory is large on DWI. 

PMID- 23965860
TI  - [Skeletal muscle MRI in a patient with neuralgic amyotrophy].
AB  - Neuralgic amyotrophy has been attributed to lesions in the brachial plexus.
      However, recent studies suggest mononeuropathy multiplex as an underlying
      pathology at least in a group of patients with neuralgic amyotrophy. We report a
      man who developed weakness of finger extensors following severe shoulder pain.
      Neurological examination revealed weakness in the muscles innervated by the left
      posterior interosseus nerve and the ulnar nerve. We diagnosed him with neuralgic
      amyotrophy based on the typical clinical course and the neurological and
      neurophysiological findings. A skeletal muscle MRI revealed abnormal high T2 and
      STIR signals in the left triceps brachialis muscle, which is innervated by a
      proximal branch of the radial nerve, and in the muscles innervated by the
      posterior interosseous and ulnar nerves. The distribution of the denervated
      muscles suggested that our patient had combined lesions of the peripheral nerve
      branches rather than the brachial plexopathy. Our report highlights the potential
      of MRI for detecting denervated muscles in neuralgic amyotrophy. 

PMID- 23965861
TI  - [A case of cerebral embolism caused by Cardiobacterium hominis endocarditis].
AB  - A 45-year-old woman was referred to our hospital by ambulance with left-sided
      palsy presented at dinner. Diffusion-weighted magnetic resonance imaging (DWI)
      showed a somewhat high intensity area in the right frontal lobe, and brain
      magnetic resonance angiography (MRA) revealed right middle cerebral artery (MCA)
      occlusion in the M1 distal segment. Although intravenous rt-PA treatment was
      initiated at 2 hours and 10 minutes after onset, recanalization was not achieved.
      The patient was diagnosed as infectious endocarditis, because highly echogenic
      vegetation was observed in the non-coronary cusp of the aortic valve;
      furthermore, Cardiobacterium hominis was incubated in blood culture, although
      fever was not so high and C-reactive protein (CRP) was not elevated at the time
      of hospitalization. It was thought that the bacteremia and infectious
      endocarditis had occurred due to tooth extraction about six months previously.
      The diagnosis of infectious endocarditis caused by the HACEK group containing C.
      hominis may become difficult because the fever was not so high and inflammation
      was not so severe. 

PMID- 23965862
TI  - [The proceedings of the 2012 Kinki Regional Post Graduate Education Meeting].

PMID- 23965863
TI  - [The proceedings of the 2012 Kyusyu Regional Post Graduate Education Meeting].

PMID- 23965864
TI  - [The proceedings of the 202nd Kanto-Koshinetsu Regional Meeting of the Japanese
      Society of Neurology].

PMID- 23965865
TI  - [The proceedings of the 199th Kyusyu Regional Meeting of the Japanese Society of
      Neurology].

PMID- 23965868
TI  - [The focus problems of diagnosis and therapy in pediatric asthma].
AB  - Childhood asthma is the most common chronic airway inflammation disease. The
      phenotypes of childhood wheezing, early diagnosis of asthma and the difficulties
      in diagnosis, tailor-made treatment and monitoring are focus problems at present.
      Early diagnosis, tailor-made treatment and dynamic monitoring are key strategies
      of asthma control. 

PMID- 23965869
TI  - [Changes in IL-17 and TGF-beta1 levels in serum and bronchoalveolar lavage fluid
      and their clinical significance among children with asthma].
AB  - OBJECTIVE: To investigate the changes in the levels of interleukin-17 (IL-17) and
      transforming growth factor beta 1 (TGF-beta1) in serum and bronchoalveolar lavage
      fluid (BALF) and their clinical significance among children with asthma. METHODS:
      Fifty-six children with asthma were divided into moderate or severe asthma (n=37)
      and mild asthma groups (n=19) and 18 children without asthma were selected as the
      control group. Cells in BALF were counted under a microscope. The levels of IL-17
      and TGF-beta1 in serum and BALF were measured using ELISA. RESULTS: were no
      significant differences in total cell count and percentage of macrophages between
      the two asthma groups and the control group (P>0.05). The percentages of
      neutrophils, eosinophils and epithelial cells in BALF were significantly higher
      in the two asthma groups than in the control group (P<0.05). The two asthma
      groups had significantly higher levels of IL-17 and TGF-beta1 in serum and BALF
      than the control group (P<0.05), and the moderate or severe asthma group had
      significantly higher levels of IL-17 and TGF-beta1 in serum and BALF than the
      mild asthma group (P<0.05). Levels of IL-17 and TGF-beta1 in serum were
      significantly positively correlated with those in BALF (r=0.935 and 0.943, P<0.05
      for both). In children with asthma, serum IL-17 level was significantly
      positively correlated with the percentage of neutrophils, eosinophils and
      epithelial cells in BALF (r=0.802, 0.799, and 0.674, P<0.05 for all), and a
      significant positive correlation was also seen between serum levels of IL-17 and
      TGF-beta1 (r=0.878, P<0.05). CONCLUSIONS: Levels of IL-17 and TGF-beta1 in serum
      and BALF are elevated in children with asthma. IL-17 and TGF-beta1 may be
      involved in the occurrence and development of asthma, and they play important
      roles in asthma attack and aggravation.

PMID- 23965870
TI  - [Epidemiological survey and analysis of asthma in children aged 0-14 years old in
      urban and rural areas of Chengdu region].
AB  - OBJECTIVE: To investigate the prevalence and incidence of asthma among children
      aged 0-14 years, with different living environments, economic levels, and
      sanitary conditions, in the urban and rural areas of Chengdu, China, and their
      influential factors. METHODS: Children aged 0-14 years who were selected from
      urban, suburban and rural areas of Chengdu, were included in the study. The
      subjects were selected from all children aged 0-14 years in schools,
      kindergartens and communities by random, cluster and non-proportional sampling.
      Parents were surveyed by questionnaire to find out suspected cases, which were
      then confirmed by inquiry and physical examination in the department of
      respiratory medicine. All the obtained data were analyzed using SPSS/PC
      statistical software. RESULTS: A total of 12082 children from the urban areas,
      5677 from suburban areas and 5590 from the rural areas were included in the
      study. Of all the subjects, 551 (4.56%) had confirmed asthma, 150 (2.64%) had
      cough variant asthma (CVA), and 142 (2.54%) had suspected asthma. The prevalence
      rate of asthma was significantly higher in the urban areas than in the suburban
      and rural areas. The correct rate of diagnosis of asthma and CVA was highest in
      the urban areas, followed by the suburban and rural areas. Use of antibiotics and
      systemic corticosteroids was most common in the rural areas, followed by the
      suburban and urban areas, but this pattern was reversed for use of inhaled
      corticosteroids and leukotriene modifier. All the results in the three areas
      demonstrated that sex, age, age at which the first attack occurred, respiratory
      tract infection, inhalation/intake of allergens and genetic factors were
      significantly associated with asthmatic attack. CONCLUSIONS: Population density,
      living environment, medical and health resources and economic level are
      associated with the prevalence and treatment of asthma.

PMID- 23965871
TI  - [Relationship between early serum lipid profiles and respiratory distress
      syndrome in preterm infants].
AB  - OBJECTIVE: To investigate early serum lipid profiles in preterm infants and their
      relationship with neonatal respiratory distress syndrome (RDS). METHODS:
      Appropriate-for-gestational-age (AGA) preterm infants were grouped according to
      gestational age (GA) or birth weight (BW). AGA full-term infants were randomly
      selected as the control group. Venous blood samples were collected within 12
      hours after birth for measurement of biochemical indices, including total
      cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density
      lipoprotein cholesterol (LDL-C) and triglyceride (TG). Blood lipid levels were
      compared between preterm infants with and without RDS in various groups. RESULTS:
      Plasma TG level rose as GA and BW increased. Plasma TG levels in the 28-30 week
      and 31-33 week GA groups were significantly lower than in the 34-36 week GA and
      control groups (P<0.01). Plasma TG levels in the <= 1499 g and 1500-2499 g BW
      groups were significantly lower than in the >= 2500 g BW and control groups
      (P<0.05), and the 1500-2499 g BW group had a significantly higher plasma TG level
      than the <= 1499 g BW group (P<0.01). There were no significant differences in
      plasma HDL-C, LDL-C and TC levels between all groups and between preterm infants
      with RDS and without RDS. In the 28-30 week GA group, the preterm infants with
      RDS had a significantly lower TG level than those without RDS (P<0.05); also, in
      the <= 1499 g BW group, preterm infants with RDS had a significantly lower TG
      level than those without RDS ( P<0.05). CONCLUSIONS: Blood lipid levels are
      related to GA and BW. Low TG level may be one of the causes of RDS in preterm
      infants with a gestational age of 28-30 weeks and a BW of <= 1499 g.

PMID- 23965872
TI  - [Changes in plasma levels of thrombomodulin and D-dimer in children with
      different types of Mycoplasma pneumoniae pneumonia].
AB  - OBJECTIVE: To investigate the changes in plasma levels of thrombomodulin (TM) and
      D-dimer (DD) in children with different types of Mycoplasma pneumoniae pneumonia
      (MPP), and their role in the pathogenesis of MPP in children. METHODS: Fifty-two
      children with MMP were divided into lobar pneumonia (n=30) and interstitial
      pneumonia groups (n=22) and another 30 healthy children were selected as the
      control group. Plasma levels of TM and D-D were measured using enzyme-linked
      immunosorbent assay and latex-enhanced immunoturbidimetric assay, respectively.
      RESULTS: The lobar pneumonia, interstitial pneumonia and control groups had
      median plasma TM levels of 23.83, 15.56 and 8.78 MUg/L respectively, with
      significant differences between the three groups (P<0.01). The lobar pneumonia
      and interstitial pneumonia groups had significantly higher plasma TM levels than
      the control group (P<0.01), and the lobar pneumonia group had a significantly
      higher plasma TM level than the interstitial pneumonia group (P<0.05). Median
      plasma D-D levels in the lobar pneumonia and interstitial pneumonia groups were
      significantly higher than the reference value (P<0.01). The lobar pneumonia group
      had a significantly higher plasma D-D level than the interstitial pneumonia group
      (0.35 MUg/mL vs 0.13 MUg/mL; P<0.01), and the percentage of patients with
      elevated plasma D-D levels was significantly higher in the lobar pneumonia group
      than in the interstitial pneumonia group (87% vs 59%; P<0.05). CONCLUSIONS:
      Children with MPP, especially those with lobar pneumonia, have increased plasma
      levels of TM and D-D. This suggests that damage to vascular endothelial cells and
      blood hypercoagulability may be involved in the pathogenesis of MPP.

PMID- 23965873
TI  - [Etiology and prevention of neonatal pneumothorax].
AB  - OBJECTIVE: To investigate the risk factors and preventative measures for neonatal
      pneumothorax. METHODS: Retrospective analysis was performed on the clinical data
      of 2286 neonates who were hospitalized in the neonatal intensive care unit
      between October 2010 and November 2011, and a case-control study was conducted to
      analyze the risk factors and preventative measures for neonatal pneumothorax.
      RESULTS: The incidence of pneumothorax among the neonates was 1.57% (36/2286),
      and it was significantly higher in full-term infants than in preterm infants
      (23/1033 vs 13/1253, P=0.023). Logistic regression analysis indicated that
      cesarean section, neonatal respiratory distress syndrome (NRDS), wet lung,
      pneumonia and mechanical ventilation were the independent risk factors for
      neonatal pneumothorax (odds ratios=7.951, 6.090, 7.898, 6.272 and 4.389; P<0.05
      for all). The higher the peak inspiratory pressure (PIP) during mechanical
      ventilation, the higher the incidence of neonatal pneumothorax (P<0.001).
      Pulmonary surfactant reduced the incidence of pneumothorax among neonates with
      NRDS (2.9% vs 10.1%; P=0.006). CONCLUSIONS: Neonatal pneumothorax occurs mostly
      in full-term infants. Cesarean section, NRDS, wet lung, pneumonia and mechanical
      ventilation are closely associated with neonatal pneumothorax. Strict management
      of indications for cesarean section, keeping PIP at a low level during mechanical
      ventilation, and use of pulmonary surfactant are helpful in preventing neonatal
      pneumothorax.

PMID- 23965874
TI  - [Ex vivo expansion and clonal variation of CD34(+)CD59(+) cells from bone marrow
      in children with paroxysmal nocturnal hemoglobinuria].
AB  - OBJECTIVE: To investigate the isolation, purification and ex vivo expansion of
      CD34(+)CD59(+) cells from the bone marrow of children with paroxysmal nocturnal
      hemoglobinuria (PNH), to evaluate the capability of long-term hematopoietic
      reconstruction of the expanded CD34(+)CD59(+) cells, and to provide a laboratory
      basis for novel treatment of PNH. METHODS: CD34(+)CD59(+) cells were isolated
      from the bone marrow mononuclear cells of children with PNH using immunomagnetic
      beads and flow cytometer in sequence. The isolated cells were subjected to ex
      vivo expansion in the presence of different combinations of hematopoietic growth
      factors for two weeks. The colony-forming cells and long-term culture-initiating
      cells (LTC-ICs) were cultured and counted. RESULTS: The optimal combination of
      hematopoietic growth factors for ex vivo expansion was stem cell
      factor+interleukin (IL)-3+IL-6+FLT3 ligand+thrombopoietin+ery-thropoietin, and
      maximum expansion (30.4 +/- 6.7 folds) was seen on day 7 of days 4 to 14 of ex
      vivo expansion. After ex vivo expansion, CD34(+)CD59(+) cells remained CD59
      positive, retained strong capability of forming colony-forming units, and could
      still form LTC-ICs. There was no significant difference in capability of forming
      LTC-ICs between CD34(+)CD59(+) cells before and after expansion. The expansion
      capability of CD34(+)CD59(+) cells from children with PNH was significantly lower
      than that of CD34(+) cells from normal controls (P<0.01). CONCLUSIONS: The
      CD34(+)CD59(+) cells from children with PNH can be expanded in vitro. Post
      expansion CD34(+)CD59(+) cells retain capability of long-term hematopoietic
      reconstruction. CD34(+)CD59(+) cells showed no trend towards PNH clone during
      culture. Ex vivo expansion of CD34(+)CD59(+) cells from children with PNH might
      be practical in performing autologous transplantation clinically for these
      children.

PMID- 23965875
TI  - [CD96 expression on leukemia stem cells in 69 children with acute leukemia].
AB  - OBJECTIVE: To detect the expression of surface molecule CD96 on stem cell (LSC)
      in children with acute leukemia, and to explore its clinical significance.
      METHODS: Bone marrow mononuclear cells were isolated in 69 children with newly
      diagnosed acute leukemia. CD34(+)CD38(-)CD123(+) LSCs were separated from these
      cells by flow cytometry (FCM) and then cultured, and CD96 expression on LSCs was
      detected by FCM. R-banding technique was used to analyze the karyotypes of the 69
      children, and the data of their routine blood and immunological tests were
      collected. RESULTS: CD96 was mainly expressed in children with acute myelogenous
      leukemia, and expressed to a lesser extent in those with acute lymphoblastic
      leukemia (P<0.05). The median expression level of CD96 in Uyghur children was
      23.4%, versus 21.2% in Han children (P>0.05). The majority of children with CD96
      positive children presented poor-prognosis karyotypes. Compared with CD96
      negative children, children with CD96-positive children had a significantly lower
      complete remission rate (P<0.05) and significantly higher infection and relapse
      rates after chemotherapy (P<0.05). CONCLUSIONS: Children with acute leukemia who
      have CD96-positive LSCs have a poor prognosis. CD96 may be a new indicator of
      prognosis in children with acute leukemia.

PMID- 23965876
TI  - [Relationship between mRNA expression and promoter methylation status of p73 gene
      in peripheral blood among children with Wilms' tumor].
AB  - OBJECTIVE: To investigate the mRNA expression and promoter methylation status of
      p73 gene in the peripheral blood of children with Wilms' tumor (WT), and their
      relationship. METHODS: Forty-five children with WT were selected as the case
      group, and 15 sex- and age- matched children (without malignancies) who visited
      the hospital for physical examination or other reasons were selected as the
      control group. Peripheral blood was collected from both groups. Real-time
      quantitative PCR and methylation-specific PCR were used to determine the mRNA
      expression level and promoter methylation status of p73 gene. Their relationship
      with clinicopathological features and the effect of promoter methylation on mRNA
      expression of p73 gene were analyzed in the case group. RESULTS: The relative
      quantity (RQ) of p73 mRNA in the case group was significantly higher than in the
      control group (3.2 +/- 0.9 vs 1.6 +/- 1.1; P<0.01). The positive rate of p73 gene
      promoter methylation in the case group was significantly lower than in the
      control group (20% vs 73%; P<0.01). In the case group, the RQ of p73 mRNA was
      significantly higher in children with methylated p73 gene promoter than in those
      with unmethylated p73 gene promoter (P<0.01). In children with methylated p73
      gene promoter, the RQ of p73 mRNA was significantly higher in the case group than
      in the control group (P<0.01). In children with unmethylated p73 gene promoter,
      there was no significant difference in RQ of p73 mRNA between the case and
      control groups (P=0.810). CONCLUSIONS: Aberrant promoter methylation of p73 gene
      in peripheral blood is one of the gene expression regulations in children with
      WT, and it is related to the onset and development of WT. The p73 gene may play a
      role as oncogene in WT patients with p73 gene promoter methylation and mRNA
      overexpression is associated with promoter methylation status of p73 gene.

PMID- 23965877
TI  - [Invasive fungal infections in the pediatric intensive care unit: a clinical
      analysis of 38 cases].
AB  - OBJECTIVE: To investigate the clinical features of invasive fungal infections
      (IFI) in the pediatric intensive care unit (PICU) and, to provide a basis for the
      effective prevention and treatment of IFI. METHODS: Retrospective analysis was
      performed on the clinical features and treatment outcomes of 38 children with IFI
      who were admitted to the PICU of Wuhan Children's Hospital between January 2009
      and August 2012. RESULTS: Pulmonary fungal infection (89%) was the most common
      among the 38 cases. Before diagnosis of IFI, all patients had severe underlying
      diseases and received several broad-spectrum antibiotics, including carbapenems,
      which were used in 95% of cases; 47% of all cases had been treated with
      corticosteroids systemically; all patients had received invasive operations, and
      47% of them had undergone endotracheal intubation and mechanical ventilation.
      None of these cases had either typical clinical symptoms and signs or specific
      imaging findings. Fifty-six strains of fungi were isolated, with Candida albicans
      (41%), Aspergilli (25%), and Mucor (20%) being the most common ones. All patients
      received timely antifungal therapies, 15 cases were cured and 16 cases showed
      improvements, with a response rate of 82%, and the rate of adverse events was
      16%. CONCLUSIONS: In the PICU, the respiratory tract is the most common site of
      IFI infection, and Candida albicans is the leading pathogen. Severe underlying
      diseases, use of broad-spectrum antibiotics and corticosteroids, and invasive
      operations are the main risk factors for IFI in the PICU. Early diagnosis and
      timely treatment with high-performance antifungal drugs can improve the prognosis
      in children with IFI.

PMID- 23965878
TI  - [Clinical and pathological features in children with progressive muscular
      dystrophy].
AB  - OBJECTIVE: To investigate the clinical and pathological features of progressive
      muscular dystrophy (PMD) in children and to provide help for the early and
      accurate diagnosis of PMD. METHODS: Retrospective analysis was performed on the
      clinical data of 99 hospitalized children with PMD, including clinical
      manifestations, age of onset, family history, creatase, electromyogram (EMG) and
      pathological changes of muscles. RESULTS: Of the 99 children with PMD, the age of
      onset was 0.5-14.5 (4.7 +/- 3.1) years. Eleven cases (11%) had a family history
      of PMD. Twenty-six (26%) were misdiagnosed as other diseases. All patients
      presented with muscle weakness when seeing the doctor, and 66 (67%) of them had
      muscle atrophy and/or hypertrophy. All patients had elevated creatine kinase (CK)
      levels. The 2-7-year-old group (n=51) had a mean CK level of 9965 +/- 8876 U/L,
      and the 7-15-year-old group (n=48) had a mean CK level of 5110 +/- 4498 U/L, with
      a significant difference between the two groups (P<0.01). The EMG examination
      performed on 66 patients showed that 54 cases (82%) had myogenic damage and 10
      cases (15%) had neurogenic damage. Light microscopy revealed coexistence of
      atrophy and hypertrophy of muscle fibers, hyaline degeneration and granular
      degeneration. Electron microscopy showed that muscle fibers were different in
      thickness, some atrophic or hypertrophic; muscle cell nuclei moved inwardly,
      myofilaments dissolved and disappeared mildly under the sarcolemma, there were
      scattered melting lesions within muscle fibers, the numbers of glycogen granules
      and mitochondria increased, mild hyperplasia and expansion of sarcoplasmic
      reticulum were seen, and a small number of muscle fibers had necrosis.
      CONCLUSIONS: Weakness of both lower extremities remains the main reason for PMD
      patients seeing the doctor. CK is the main laboratory indicator for diagnosis of
      PMD. PMD is mainly manifested as myogenic damage in the early stage and may be
      accompanied by neurogenic damage in the late stage, according to the EMG
      examination. With a high misdiagnosis rate, PMD may be misdiagnosed as many other
      diseases. Pathological examination under light microscope and electron microscope
      is the main means for confirming a PMD diagnosis.

PMID- 23965879
TI  - [Auditory event-related potentials in children with functional articulation
      disorders].
AB  - OBJECTIVE: To investigate the central auditory processing function in children
      with functional articulation disorders (FAD), and possible causes of FAD.
      METHODS: Twenty-seven children with FAD were selected as the case group and 50
      age-matched normal children were selected as the control group. The two groups
      were compared with respect to the following factors: percentage of individuals
      with a positive history of language development disorder, and the form, peak
      latency and peak amplitude of mismatch negativity (MMN) on auditory event-related
      potentials. RESULTS: Compared with the control group, the case group had a
      significantly higher percentage of individuals with a positive history of
      language development disorder (70% vs 8%; P<0.01), a significantly prolonged peak
      latency of MMN (209 +/- 31 ms vs 175 +/- 32 ms; P<0.01), and an insignificantly
      lower peak amplitude of MMN (P>0.05). CONCLUSIONS: Prolonged central auditory
      processing may be one of the causes of FAD in children.

PMID- 23965880
TI  - [Epidemiological investigation of tic disorders among pupils in the Shunde
      Longjiang area, and their relationship to trace elements].
AB  - OBJECTIVE: To investigate the epidemiological characteristics of tic disorders
      (TD) among pupils in the Shunde Longjiang area, and their relationship to trace
      elements. METHODS: A cross-sectional study of 4062 children aged 6-12 years, who
      were selected from the Shunde Longjiang area by stratified cluster sampling to
      investigate the epidemiological characteristics of TD, was conducted, and blood
      concentrations of trace elements in children with TD were determined. Forty
      normal children were selected as controls. RESULTS: The overall prevalence rate
      of TD was 2.98%; the prevalence rates of transient tic disorder, chronic motor or
      vocal tic disorder and Tourette's syndrome were 3.62%, 2.39% and 1.21%
      respectively. Boys had a significantly higher prevalence rate of TD than girls
      (3.92% vs 1.96%; P<0.05). There were no significant differences in blood copper,
      manganese and magnesium levels between children with TD and normal children
      (P>0.05), however, children with TD had a significantly increased blood lead
      level and significantly decreased blood zinc and iron levels compared with the
      normal children (P<0.05). No significant differences in trace elements were found
      between children with different subtypes of TD (P>0.05). CONCLUSIONS: TD is
      common in children aged 6-12 years and more prevalent in boys than in girls. High
      blood lead level and zinc and iron deficiencies may be one of the causes of TD,
      and thus should be considered during therapy.

PMID- 23965881
TI  - [Gene mutations and clinical manifestations in children with glycogen storage
      disease type Ib].
AB  - OBJECTIVE: Glycogen storage disease type Ib (GSDIb) is caused by a deficiency of
      glucose-6-phosphate translocase (G6PT) activity due to SLC37A4 gene mutations.
      Most GSDIb patients have recurrent infections and inflammatory bowel disease,
      with poor prognosis. Detection of SLC37A4 gene mutations is of great significance
      for the diagnosis, subtyping and outcome prediction of GSD patients. This study
      aims to analyze SLC37A4 gene mutations in Chinese GSDIb patients and to
      investigate the relationship between its genotypes and clinical manifestations.
      METHODS: All exons and their flanking introns of SLC37A4 gene in 28 Chinese
      children with a primary diagnosis of GSDIb were screened by PCR combined with
      direct DNA sequencing to detect SLC37A4 gene mutations. RESULTS: Five SLC37A4
      gene mutations were detected in 7 (25%) of the 28 children, i.e., p.Gly149Glu
      (9/13, 69%), p.Gly115Arg (1/13, 8%), p.Pro191Leu (1/13, 8%), c.959-960 insT
      (1/13, 8%) and c.870+5G>A (1/13, 8%). CONCLUSIONS: In this study, c.959-960 insT
      is a novel mutation and p.Gly149Glu is the most common mutation. p.Gly149Glu may
      be associated with severe infections in children with GSDIb.

PMID- 23965882
TI  - [Clinical efficacy of mycophenolate mofetil in the treatment of systemic-onset
      juvenile idiopathic arthritis].
AB  - OBJECTIVE: To evaluate the clinical efficacy of mycophenolate mofetil (MMF) in
      the treatment of systemic-onset juvenile idiopathic arthritis (SoJIA). METHODS:
      Thirty-five patients with a confirmed diagnosis of SoJIA who had received initial
      treatment were randomly divided into control (n=15), MMF1 (n=7) and MMF2 groups
      (n=13). The control group received conventional treatment, the MMF1 group
      received MMF after 2 weeks of conventional treatment that had not led to
      remission, and the MMF2 group received combination therapy with non-steroidal
      anti-inflammatory drugs, prednisone and MMF. Symptoms, signs, laboratory indices,
      and adverse events were observed after 2, 4, and 12 weeks of treatment, and
      follow-up was performed for 3-6 months. RESULTS: Before treatment, the MMF2 group
      had a significantly longer disease course than the control group (P<0.05). After
      2 weeks of treatment, the MMF1 and MMF2 groups had a significantly lower
      prednisone dose and erythrocyte sedimentation rate (ESR) than the control group
      (P<0.05). The MMF1 group had significantly higher body temperature than the other
      two groups (P<0.05). After 4 weeks of treatment, the MMF1 group had a
      significantly lower prednisone dose and ESR than the control group (P<0.05). The
      MMF2 group had a significantly lower prednisone dose, body temperature (recovery
      to normal), white blood cell count, ESR and serum ferritin concentration than the
      control group (P<0.05). Body temperature was significantly lower in the MMF2
      group than in the MMF1 group (P<0.05). No adverse events were observed in either
      the MMF1 or MMF2 groups during treatment. CONCLUSIONS: Combination therapy with
      MMF can lead to better control of the patient's condition, more rapid relief of
      clinical symptoms and reduced glucocorticoid dose. The therapy with MMF is safe
      in children.

PMID- 23965883
TI  - [Long-term outcomes and factors for predicting ventricular arrhythmia in patients
      with catecholaminergic polymorphic ventricular tachycardia].
AB  - OBJECTIVE: To evaluate factors for predicting ventricular arrhythmia, the
      clinical effect of drugs on patients with catecholaminergic polymorphic
      ventricular tachycardia (CPVT), and their long-term outcomes. METHODS: Six
      patients diagnosed with CPVT underwent a series of electrocardiograms and 24-hour
      Holter monitoring. beta-blockers were recommended for all patients, while some
      patients were also prescribed propafenone and 1 patient underwent catheter-based
      renal sympathetic denervation (RDN). The characteristics of electrocardiogram,
      arrhythmia and long-term outcomes were monitored. RESULTS: Syncope episodes did
      not occur any longer in 1 patient on beta-blocker, but recurred in 3 other
      patients and 2 patients died (one due to his cessation of metoprolol for 3
      months). Inverted and/or bifid T waves and abnormal U wave were observed in the
      precordial leads. T wave alternans was observed in 4 patients in the precordial
      leads. These abnormal electrocardiogram features disappeared or diminished with
      beta-blocker treatment. All spontaneous episodes of ventricular tachycardia
      occurred prior to sinus tachycardia and frequent polymorphic premature
      ventricular contractions. CONCLUSIONS: Bifid and/or inverted T waves, T wave
      alternans and abnormal U waves together with sinus tachycardia and frequent
      premature ventricular contractions are indicator for predicting ventricular
      arrhythmia and assessing the effect of beta-blockers. Compliance with beta
      blocker treatment is a strong indicator of outcome.

PMID- 23965884
TI  - [Relationship between bone turnover markers and bone sound of speed in
      appropriate-for-gestational-age neonates].
AB  - OBJECTIVE: To investigate the correlation of gestational age (GA) with
      carboxyterminal propeptide of type I procollagen (PICP), deoxypyridinoline (DPD),
      and bone sound of speed (SOS) in appropriate-for-gestational-age (AGA) neonates,
      as well as the relationship between bone turnover markers and bone SOS. METHODS:
      Sixty-five AGA neonates were included in the study. The neonates were divided
      into three groups: preterm infant (GA <=3 4 weeks, 14 cases), late preterm infant
      (34 weeks<GA<37 weeks, 13 cases), and full-term infant (GA >= 37 weeks, 38
      cases). Birth weight and length were measured in all cases, and Ponderal index
      (PI) was used to estimate their nutritional status. Venous blood was collected
      within 7 days after birth to measure blood PICP concentration. Urine was
      collected to measure urinary DPD and creatinine (Cr) levels. Omnisense 7000P
      ultrasound bone sonometer was applied to measure the SOS of the left tibia in all
      cases within 7 days after birth. RESULTS: There were significant differences in
      GA (F=140.199, P<0.001), birth weight (F=47.042, P<0.001), birth length
      (F=46.877, P<0.001), and PI (F=11.898, P<0.001) between the three groups; the
      higher the GA, the higher the birth weigh, birth length, and PI. There were
      significant differences in PICP (F=30.384, P<0.001), DPD/Cr (F=21.761, P<0.001),
      and SOS (F=20.052, P<0.001) between the three groups; the higher the GA, the
      lower the PICP and DPD/Cr and the higher the bone SOS. PICP and DPD/Cr were
      negatively correlated with GA, birth weight and bone SOS (P<0.01), while bone SOS
      was positively correlated with GA and birth weight (P<0.01), which still held
      true after adjustment for GA and birth weight. CONCLUSIONS: Among AGA neonates,
      bone turnover markers are negatively correlated with GA, birth weight and bone
      SOS. High bone turnover is bad for bone health in AGA neonates.

PMID- 23965885
TI  - [Effects of L-Arg on expression of PI3K and PKB in liver among low-birth-weight
      newborn rats].
AB  - OBJECTIVE: To measure the expression of phosphatidylinositol 3-kinase (PI3K) and
      protein kinase B (PKB) in liver tissue among low-birth-weight newborn rats
      treated with L-arginine (L-Arg) in early life, and to investigate the effect of L
      Arg on insulin resistance. METHODS: Eighteen pregnant rats were randomly divided
      into three groups: control, model and intervention (n=6 each). The control group
      was fed with normal protein feed (protein content=21%) during pregnancy to
      establish a normal-birth-weight newborn rat model, and the model and intervention
      groups were fed with low-protein feed (protein content=10%) during pregnancy to
      establish a low-birth-weight newborn rat model. Newborn rats from the three
      pregnant rat groups were also assigned to control, model and intervention groups.
      During 21 days of lactation, maternal rats in the control and model groups were
      fed with normal protein feed and normal drinking water, while maternal rats in
      the intervention group were fed with normal protein feed and drinking water rich
      in L-Arg (200 mg/kg.d). After ablactation, the three groups of newborn rats were
      fed with normal protein feed and normal drinking water. Liver tissue samples were
      collected from these newborn rats at 1, 3 and 8 weeks after birth. Protein
      expression of PI3K and PKB in liver tissue was measured by Western blot. RESULTS:
      At 1 week after birth, the newborn rats in the intervention group had
      significantly higher protein expression of PI3K than in the model group
      (P=0.045), but there was no significant difference when compared with the control
      group (P=0.503). At 8 weeks after birth, the newborn rats in the intervention
      group had significantly higher protein expression of PKB than the model group
      (P=0.039), but there was no significant difference when compared with the control
      group (P>0.05). CONCLUSIONS: A supplement of L-Arg in early life can boost
      protein synthesis, increase protein expression of PI3K and PKB in liver tissue,
      promote insulin signaling and reduce insulin resistance.

PMID- 23965886
TI  - [HLH-2004 protocol: diagnostic and therapeutic guidelines for childhood
      hemophagocytic lymphohistiocytosis].

PMID- 23965887
TI  - [Clinical analysis of 23 cases of pediatric chronic lymphocytic thyroiditis].

PMID- 23965888
TI  - [Pediatric acute disseminated encephalomyelitis: clinical features and follow-up
      study in 39 cases].

PMID- 23965889
TI  - [Ceftriaxone-associated biliary pseudolithiasis in a child with nephrotic
      syndrome].

PMID- 23965890
TI  - [Relationship between vitamin D and autism spectrum disorder].
AB  - Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, with
      multiple genetic and environmental risk factors. The interplay between genetic
      and environmental factors has become the subject of intensified research in the
      last several years. Vitamin D deficiency has recently been proposed as a possible
      environmental risk factor for ASD. Vitamin D has a unique role in brain
      homeostasis, embryogenesis and neurodevelopment, immunological modulation
      (including the brain's immune system), antioxidation, antiapoptosis, neural
      differentiation and gene regulation. Children with ASD had significantly lower
      serum levels of 25-hydroxy vitamin D than healthy children.Therefore vitamin D
      deficiency during pregnancy and early childhood may be an environmental trigger
      for ASD. 

PMID- 23965891
TI  - [Advances in medical care for extremely low birth weight infants worldwide].
AB  - Dramatic advances in neonatal medicine over recent decades have resulted in
      decreased mortality and morbidity rates for extremely low birth weight infants.
      However, the survival of these infants is associated with short- and long-term
      morbidity, including severe intraventricular hemorrhage, periventricular
      leukomalacia, nosocomial infection and necrotizing enterocolitis,
      bronchopulmonary dysplasia, retinopathy of prematurity and adverse long-term
      neurodevelopmental sequelae. This article reviewed the latest advances in the
      medical care for extremely low birth weight infants including survival rate,
      ethical issues and short- and long-term morbidity, domestically and abroad. 

PMID- 23965892
TI  - [Summary of the 9th international symposium on antimicrobial agents and
      resistance].

PMID- 23965893
TI  - The osseointegration of zirconia dental implants.
AB  - Zirconia is currently extensively used in medicine, especially in orthopedic
      surgery for various joint replacement appliances. Its outstanding mechanical and
      chemical properties have made it the "material of choice" for various types of
      prostheses. Its color in particular makes it a favored material to manufacture
      dental implants. A literature search through Medline enables one to see
      zirconia's potential but also to point out and identify its weaknesses. The
      search shows that zirconia is a biocompatible, osteoconductive material that has
      the ability to osseointegrate. Its strength of bonding to bone depends on the
      surface structure of the implant. Although interesting, the studies do not allow
      for the recommendation of the use of zirconia implants in daily practice. The
      lack of studies examining the chemical and structural composition of zirconia
      implants does not allow for a "gold standard" to be established in the implant
      manufacturing process. Randomized clinical trials (RCT) are urgently needed on
      surface treatments of zirconia implants intended to achieve the best possible
      osseointegration.

PMID- 23965894
TI  - Factors associated with adoption of robotic surgical technology in US hospitals
      and relationship to radical prostatectomy procedure volume.
AB  - OBJECTIVE: Robotic technology has diffused rapidly despite high costs and limited
      additive reimbursement by major payers. We aimed to identify the factors
      associated with hospitals' decisions to adopt robotic technology and the
      consequences of these decisions. METHODS: This observational study used data on
      hospitals and market areas from 2005 to 2009. Included were hospitals in census
      based statistical areas within states in the State Inpatient Database that
      participated in the American Hospital Association annual surveys and performed
      radical prostatectomies. The likelihood that a hospital would acquire a robotic
      facility and the rates of radical prostatectomy relative to the prevalence of
      robots in geographic market areas were assessed using multivariable analysis.
      RESULTS: Hospitals in areas where a higher proportion of other hospitals had
      already acquired a robot were more likely to acquire one (P=0.012), as were those
      with more than 300 beds (P<0.0001) and teaching hospitals (P<0.0001). There was a
      significant association between years with a robot and the change in the number
      of radical prostatectomies (P<0.0001). More radical prostatectomies were
      performed in areas where the number of robots per 100,000 men was higher
      (P<0.0001). Adding a single robot per 100,000 men in an area was associated with
      a 30% increase in the rate of radical prostatectomies. CONCLUSIONS: Local area
      robot competition was associated with the rapid spread of robot technology in the
      United States. Significantly more radical prostatectomies were performed in
      hospitals with robots and in market areas of hospitals with robotic technology.

PMID- 23965895
TI  - Establishing the suitability of quantitative optical CT microscopy of PRESAGE(r)
      radiochromic dosimeters for the verification of synchrotron microbeam therapy.
AB  - Previous research on optical computed tomography (CT) microscopy in the context
      of the synchrotron microbeam has shown the potential of the technique and
      demonstrated high quality images, but has left two questions unanswered: (i) are
      the images suitably quantitative for 3D dosimetry? and (ii) what is the impact on
      the spatial resolution of the system of the limited depth-of-field of the
      microscope optics? Cuvette and imaging studies are reported here that address
      these issues. Two sets of cuvettes containing the radiochromic plastic PRESAGE(r)
      were irradiated at the ID17 biomedical beamline of the European Synchrotron
      Radiation facility over the ranges 0-20 and 0-35 Gy and a third set of cuvettes
      was irradiated over the range 0-20 Gy using a standard medical linac. In
      parallel, three cylindrical PRESAGE(r) samples of diameter 9.7 mm were irradiated
      with test patterns that allowed the quantitative capabilities of the optical CT
      microscope to be verified, and independent measurements of the imaging modulation
      transfer function (MTF) to be made via two different methods. Both
      spectrophotometric analysis and imaging gave a linear dose response, with
      gradients ranging from 0.036-0.041 cm(-1) Gy(-1) in the three sets of cuvettes
      and 0.037 (optical CT units) Gy(-1) for the imaging. High-quality, quantitative
      imaging results were obtained throughout the 3D volume, as illustrated by depth
      dose profiles. These profiles are shown to be monoexponential, and the linear
      attention coefficient of PRESAGE(r) for the synchrotron-generated x-ray beam is
      measured to be (0.185 +/- 0.02) cm(-1) in excellent agreement with expectations.
      Low-level (<5%) residual image artefacts are discussed in detail. It was possible
      to resolve easily slit patterns of width 37 um (which are smaller than many of
      the microbeams used on ID-17), but some uncertainty remains as to whether the low
      values of MTF for the higher spatial frequencies are scanner related or a result
      of genuine (but non-ideal) dose distributions. We conclude that microscopy images
      from our scanner do indeed have intensities that are proportional to
      spectrophotometric optical density and can thus be used as the basis for accurate
      dosimetry. However, further investigations are necessary before the microscopy
      images can be used to make the quantitative measures of peak-to-valley ratios for
      small-diameter microbeams. We suggest various strategies for moving forward and
      are optimistic about the future potential of this system. 

PMID- 23965896
TI  - Antipsychotics and the risk of type 2 diabetes mellitus in children and youth.
AB  - IMPORTANCE: The increased prescribing of antipsychotics for children and youth
      has heightened concerns that this practice increases the risk of type 2 diabetes
      mellitus. OBJECTIVE: To compare the risk of type 2 diabetes in children and youth
      6 to 24 years of age for recent initiators of antipsychotic drugs vs propensity
      score-matched controls who had recently initiated another psychotropic
      medication. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of the
      Tennessee Medicaid program with 28 858 recent initiators of antipsychotic drugs
      and 14 429 matched controls. The cohort excluded patients who previously received
      a diagnosis of diabetes, schizophrenia, or some other condition for which
      antipsychotics are the only generally recognized therapy. MAIN OUTCOMES AND
      MEASURES: Newly diagnosed diabetes during follow-up, as identified from diagnoses
      and diabetes medication prescriptions. RESULTS: Users of antipsychotics had a 3
      fold increased risk for type 2 diabetes (HR = 3.03 [95% CI = 1.73-5.32]), which
      was apparent within the first year of follow-up (HR = 2.49 [95% CI = 1.27-4.88]).
      The risk increased with cumulative dose during follow-up, with HRs of 2.13 (95%
      CI = 1.06-4.27), 3.42 (95% CI = 1.88-6.24), and 5.43 (95% CI = 2.34-12.61) for
      respective cumulative doses (gram equivalents of chlorpromazine) of more than 5
      g, 5 to 99 g, and 100 g or more (P < .04). The risk remained elevated for up to 1
      year following discontinuation of antipsychotic use (HR = 2.57 [95% CI = 1.34
      4.91]). When the cohort was restricted to children 6 to 17 years of age,
      antipsychotic users had more than a 3-fold increased risk of type 2 diabetes (HR
      = 3.14 [95% CI = 1.50-6.56]), and the risk increased significantly with
      increasing cumulative dose (P < .03). The risk was increased for use restricted
      to atypical antipsychotics (HR = 2.89 [95% CI = 1.64-5.10]) or to risperidone (HR
      = 2.20 [95% CI = 1.14-4.26]). CONCLUSIONS AND RELEVANCE: Children and youth
      prescribed antipsychotics had an increased risk of type 2 diabetes that increased
      with cumulative dose.

PMID- 23965897
TI  - A novel local anti-colorectal cancer drug delivery system: negative lipidoid
      nanoparticles with a passive target via a size-dependent pattern.
AB  - The nontoxic, targeted and effective delivery of nucleic acid drugs remains an
      important challenge for clinical development. Here, we describe a novel negative
      lipidoid nanoparticle delivery system, providing entrapment-based transfection
      agents for local delivery of siRNA to the colorectal cancer focus. The delivery
      system was synthesized with lipidoid material 98N12-5(1), mPEG2000-C12/C14
      glyceride and cholesterol at a desired molar ratio to realize the anionic surface
      charge of particles, which could alleviate to a larger degree the inflammatory
      response and immune stimulation of the organism, embodying dramatic
      biocompatibility. In particular, mPEG2000-C12/C14 glyceride was selected to
      ameliorate the stability of the delivery system and protection of nucleic acids
      by extending the tail length of the carbons, crucial also to neutralize the
      positive charge of 98N12-5(1) to form a resultant anionic particle. In vivo
      experiments revealed that a particle size of 90 nm perfectly realized a passive
      target in a size-dependent manner and did not affect the function of the liver
      and kidneys by a local delivery method, enema. We clarified that the uptake of
      negative lipidoid nanoparticles internalized through a lipid raft endocytotic
      pathway with low cytotoxicity, strong biocompatibility and high efficacy. This
      study suggests that negative lipidoid nanoparticles with enema delivery
      constitute, uniquely and appropriately, a local anti-colorectal cancer nucleic
      acid drug delivery platform, and the application of similar modes may be feasible
      in other therapeutic settings.

PMID- 23965898
TI  - New strategies in neuroblastoma: Therapeutic targeting of MYCN and ALK.
AB  - Clinical outcome remains poor in patients with high-risk neuroblastoma, in which
      chemoresistant relapse is common following high-intensity conventional multimodal
      therapy. Novel treatment approaches are required. Although recent genomic
      profiling initiatives have not revealed a high frequency of mutations in any
      significant number of therapeutically targeted genes, two exceptions,
      amplification of the MYCN oncogene and somatically acquired tyrosine kinase
      domain point mutations in anaplastic lymphoma kinase (ALK), present exciting
      possibilities for targeted therapy. In contrast with the situation with ALK, in
      which a robust pipeline of pharmacologic agents is available from early clinical
      use in adult malignancy, therapeutic targeting of MYCN (and MYC oncoproteins in
      general) represents a significant medicinal chemistry challenge that has remained
      unsolved for two decades. We review the latest approaches envisioned for blockade
      of ALK activity in neuroblastoma, present a classification of potential
      approaches for therapeutic targeting of MYCN, and discuss how recent developments
      in targeting of MYC proteins seem to make therapeutic inhibition of MYCN a
      reality in the clinic.

PMID- 23965899
TI  - Promoter CpG island methylation of genes in key cancer pathways associates with
      clinical outcome in high-grade serous ovarian cancer.
AB  - PURPOSE: We aimed to identify DNA methylation biomarkers of progression-free
      survival (PFS) to platinum-based chemotherapy in high-grade serous ovarian cancer
      (HGSOC) within biologically relevant ovarian cancer-associated pathways.
      EXPERIMENTAL DESIGN: Association with PFS of CpG island (CGI) promoter DNA
      methylation at genes in the pathways Akt/mTOR, p53, redox, and homologous
      recombination DNA repair was sought with PFS as the primary objective in a
      prospectively collected ovarian cancer cohort (n = 150). Significant loci were
      validated for associations between PFS, methylation, and gene expression in an
      independent The Cancer Genome Atlas (TCGA) data set of HGSOC (n = 311). RESULTS:
      DNA methylation at 29 CGI loci linked to 28 genes was significantly associated
      with PFS, independent from conventional clinical prognostic factors (adjusted P <
      0.05). Of 17 out of the 28 genes represented in the TCGA data set, methylation of
      VEGFB, VEGFA, HDAC11, FANCA, E2F1, GPX4, PRDX2, RAD54L, and RECQL4 was prognostic
      in this independent patient cohort (one-sided P < 0.05, false discovery rate <
      10%). A multivariate Cox model was constructed, with clinical parameters (age,
      stage, grade, and histologic type) and significant loci. The final model included
      NKD1, VEGFB, and PRDX2 as the three best predictors of PFS (P = 6.62 * 10(-6),
      permutation test P < 0.05). Focussing only on known VEGFs in the TCGA cohort
      showed that methylation at promoters of VEGFA, VEGFB, and VEGFC was significantly
      associated with PFS. CONCLUSIONS: A three loci model of DNA methylation could
      identify two distinct prognostic groups of patients with ovarian cancer (PFS: HR
      = 2.29, P = 3.34 * 10(-5); overall survival: HR = 1.87, P = 0.007) and patients
      more likely to have poor response to chemotherapy (OR = 3.45, P = 0.012).

PMID- 23965900
TI  - Intratumoral anti-CTLA-4 therapy: enhancing efficacy while avoiding toxicity.
AB  - Systemic administration of the checkpoint blockade antibody anti-CTLA4 results in
      severe autoimmune toxicity, limiting its clinical efficacy. Fransen and
      colleagues show here that peritumoral delivery of low doses of this
      immunomodulatory drug can trigger a systemic antitumor immune response while
      preventing the toxicity against other organs.

PMID- 23965902
TI  - Pralatrexate pharmacology and clinical development.
AB  - Folates are well known to be essential for many cellular processes, including
      cellular proliferation. As a consequence, antifolates, the fraudulent mimics of
      folic acid, have been shown to be potent therapeutic agents in many cancers. Over
      the past several decades, efforts to improve on this class of drugs have met with
      little success. Recently, one analog specifically designed to have high affinity
      for the reduced folate carrier, which efficiently internalizes natural folates
      and antifolates, has been shown to be very active in T-cell lymphoma.
      Pralatrexate, approved by the U.S. Food and Drug Administration in 2009, is
      highly active across many lymphoid malignancies, including chemotherapy-resistant
      T-cell lymphoma. Emerging combination studies have now shown that pralatrexate is
      highly synergistic with gemcitabine, histone deacetylase inhibitors like
      romidepsin and bortezomib. These insights are leading to a number of novel phase
      I and II combination studies which could challenge existing regimens like CHOP,
      and improve the outcome of patients with T-cell lymphoma.

PMID- 23965901
TI  - Phase II trial of bicalutamide in patients with androgen receptor-positive,
      estrogen receptor-negative metastatic Breast Cancer.
AB  - PURPOSE: Patients with hormone receptor-negative breast cancer generally do not
      benefit from endocrine-targeted therapies. However, a subset with androgen
      receptor (AR) expression is predicted to respond to antiandrogen therapies. This
      phase II study explored bicalutamide in AR-positive, estrogen receptor (ER), and
      progesterone receptor (PgR)-negative metastatic breast cancer. EXPERIMENTAL
      DESIGN: Tumors from patients with ER/PgR-negative advanced breast cancer were
      tested centrally for AR [immunohistochemistry (IHC) > 10% nuclear staining
      considered positive]. If either the primary or a metastatic site was positive,
      patients were eligible to receive the AR antagonist bicalutamide at a dose of 150
      mg daily. Clinical benefit rate (CBR), the primary endpoint, was defined as the
      total number of patients who show a complete response (CR), partial response
      (PR), or stable disease (SD) > 6 months; secondary endpoints included progression
      free survival (PFS) and toxicity. Correlative studies included measurement of
      circulating endocrine markers and IHC surrogates for basal-like breast cancer.
      RESULTS: Of 424 patients with ER/PgR-negative breast cancer, 12% tested AR
      positive. The 6-month CBR was 19% [95% confidence interval (CI), 7%-39%] for
      bicalutamide. The median PFS was 12 weeks (95% CI, 11-22 weeks). Bicalutamide was
      well-tolerated with no grade 4/5 treatment-related adverse events observed.
      CONCLUSION: AR was expressed in 12% of patients with ER/PgR-negative breast
      cancer screened for this trial. The CBR of 19% observed with bicalutamide shows
      proof of principle for the efficacy of minimally toxic androgen blockade in a
      select group of patients with ER/PgR-negative, AR-positive breast cancer.

PMID- 23965903
TI  - Impact of c-MYC protein expression on outcome of patients with early-stage HER2+
      breast cancer treated with adjuvant trastuzumab NCCTG (alliance) N9831.
AB  - PURPOSE: This study investigated the association between tumor MYC protein
      expression and disease-free survival (DFS) of patients randomized to receive
      chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent
      trastuzumab (Arm C) in the N9831 (Alliance) adjuvant HER2(+) trastuzumab breast
      cancer trial. EXPERIMENTAL DESIGN: This analysis included 1,736 patients
      randomized to Arms A, B, and C on N9831. Nuclear MYC protein expression was
      determined in tissue microarray sections containing three biopsies per patient or
      whole tissue sections using standard immunohistochemistry (clone 9E10). A tumor
      was considered positive for MYC protein overexpression (MYC(+)) if the nuclear 3+
      staining percentage was more than 30%. RESULTS: Five hundred and seventy-four
      (33%) tumors were MYC(+). MYC(+) was associated with hormone receptor positivity
      (chi(2), P = 0.006), tumors 2 cm or more (chi(2), P = 0.02), and a higher rate of
      nodal positivity (chi(2), P < 0.001). HRs for DFS (median follow-up: 6.1 years)
      for Arm C versus A were 0.52 (P = 0.006) and 0.65 (P = 0.006) for patients with
      MYC(+) and MYC(-) tumors, respectively (P(interaction) = 0.40). For Arm B versus
      A, HRs for patients with MYC(+) and MYC(-) tumors were 0.79 (P = 0.21) and 0.74
      (P = 0.04), respectively (P(interaction) = 0.71). For Arm C versus B, HRs for
      patients with MYC(+) and MYC(-) tumors were 0.56 (P = 0.02) and 0.89 (P = 0.49),
      respectively (P(interaction) = 0.17). CONCLUSIONS: Our data do not support an
      impact of tumor MYC protein expression on differential benefit from adjuvant
      trastuzumab.

PMID- 23965905
TI  - The evolution of Negative Pressure Wound Therapy [NPWT1: a review of science,
      available devices, and evolution in the usage of NPWT.
AB  - Negative Pressure Wound Therapy (NPWT) is an important clinical tool with
      multiple published studies reporting more rapid formation of granulation tissue
      and a decreased time for wound healing.Since the induction of NPWT systems in
      1995, there has been wide usage of the device for treatment of wounds. However,
      the past 18 years has also witnessed a significant shift in the way NPWT is
      utilized. Meeting the demands and wound care needs of an ever-growing population
      has resulted in several other companies releasing their versions of the NWPT
      device. Although there is a significant body of literature supporting the science
      and clinical advantages of the KCI system, the newer systems differ in terms of
      suction devices, connecting tubing, and wound interface materials. It cannot be
      assumed that the newly developed devices have the same science and clinical
      advantages as the KCI System. The purpose of this article is to review the
      science behind NPWT, assess and compare the currently available devices, and
      examine the scientific literature supporting the efficiency and application of
      NPWT in wound reconstruction.

PMID- 23965904
TI  - Molecular pathways: Estrogen pathway in colorectal cancer.
AB  - Worldwide, colorectal cancer has a higher incidence rate in men than in women,
      suggesting a protective role for sex hormones in the development of the disease.
      Preclinical data support a role for estrogen and its receptors in the initiation
      and progression of colorectal cancer and establishes that protective effects of
      estrogen are exerted through ERbeta. Hormone replacement therapy (HRT) in
      postmenopausal women as well as consumption of soy reduces the incidence of
      colorectal cancer. In the Women's Health Initiative trial, use of HRT in
      postmenopausal women reduced the risk of colon cancer by 56% [95% confidence
      interval (CI), 0.38-0.81; P = 0.003]. A recent meta-analysis showed that in
      women, consumption of soy reduced the risk of colon cancer by 21% (95% CI, 0.03
      0.35; P = 0.026). In this review, using the preclinical data, we translate the
      findings in the clinical trials and observational studies to define the role of
      estrogen in the prevention of colorectal cancer. We hypothesize that sometime
      during the tumorigenesis process ERbeta expression in colonocytes is lost and the
      estrogen ligand, HRT, or soy products, exerts its effects through preventing this
      loss. Thus, in the adenoma-to-carcinoma continuum, timing of HRT is a significant
      determinant of the observed benefit from this intervention. We further argue that
      the protective effects of estrogen are limited to certain molecular subtypes.
      Successful development of estrogen modulators for prevention of colorectal cancer
      depends on identification of susceptible colorectal cancer population(s). Thus,
      research to better understand the estrogen pathway is fundamental for clinical
      delivery of these agents.

PMID- 23965906
TI  - The use of barbed suture in bladder and bowel surgery.
AB  - A new class of suturing material, barbed suture, was recently added to the
      surgeon's armamentarium. It was initially used in open surgery for soft tissue
      approximation. Its applications in laparoscopic surgery quickly flourished
      because it eliminates the time-consuming process of extracorporeal and
      intracorporeal knot tying. Data supporting the use of barbed suture for the
      repair of bladder and bowel injuries is still scarce. As a matter of fact, many
      surgeons still use conventional sutures, secured with knots, when facing a
      cystotomy or an enterotomy. Choosing the best suture material for a specific
      surgical procedure lies in a thorough understanding of the suture properties. In
      this article, we shed light on the characteristics that make barbed suture
      attractive for bladder and bowel repair and illustrate our surgical approach for
      cystotomy and enterotomy repair using this novel suture material. Based on our
      experience at Magee-Womens Hospital, barbed suture provides adequate tension-free
      repairs and improves the efficiency of laparoscopic suturing when closing bladder
      or bowel defects. As we have so far not encountered any complications, we
      conclude that repairing cystotomies and enterotomies with barbed suture is
      feasible and safe. 

PMID- 23965907
TI  - Effect of the vegetarian diet on non-communicable diseases.
AB  - A vegetarian diet generally includes plenty of vegetables and fruits, which are
      rich in phytochemicals, antioxidants, fiber, magnesium, vitamins C and E, Fe3+,
      folic acid and n-6 polyunsaturated fatty acid (PUFA), and is low in cholesterol,
      total fat and saturated fatty acid, sodium, Fe2+, zinc, vitamin A, B12 and D, and
      especially n-3 PUFA. Mortality from all-cause, ischemic heart disease, and
      circulatory and cerebrovascular diseases was significantly lower in vegetarians
      than in omnivorous populations. Compared with omnivores, the incidence of cancer
      and type 2 diabetes was also significantly lower in vegetarians. However,
      vegetarians have a number of increased risk factors for non-communicable diseases
      such as increased plasma homocysteine, mean platelet volume and platelet
      aggregability compared with omnivores, which are associated with low intake of
      vitamin B12 and n-3 PUFA. Based on the present data, it would seem appropriate
      for vegetarians to carefully design their diet, specifically focusing on
      increasing their intake of vitamin B12 and n-3 PUFA to further reduce already low
      mortality and morbidity from non-communicable diseases.

PMID- 23965909
TI  - Positive communication paradigm decreases early recurrence in clubfoot treatment.
AB  - BACKGROUND: The Ponseti method has become the treatment standard for idiopathic
      clubfoot. Deformity recurrence is most commonly attributed to premature
      abandonment of the requisite abduction orthosis. A study in 2009 from our center
      revealed a high rate of deformity recurrence in our patient population. It was
      surmised that the importance of bracing to maintain correction had not been
      adequately communicated to some families, especially Native Americans. As a
      result, the principal investigator developed a different communication protocol
      for parents of infants. METHODS: All children treated for clubfoot at the
      University of New Mexico Carrie Tingley Hospital, Albuquerque, NM, from 2008 to
      2010 were reviewed. They were compared with a historical control group from this
      institution, the subjects of the 2009 study, and were analyzed for the rate of
      recurrence and Pirani score improvement. RESULTS: Our study cohort comprised 69
      infants (104 clubfeet), all of whom were treated with the new communication
      style. The recurrence rate for the new communication paradigm was 2.88% compared
      with 18.2% in the control group (P<0.001). The Pirani score improvement was 4.0
      in the treatment group compared with 3.5 in the control group (P=0.001). Native
      American recurrence was zero in the treatment group and 41% in the control group
      (P=0.011). CONCLUSIONS: A positive, rather than a negative communication style,
      emphasis on the brace as the most important aspect of treatment, and a more
      culturally sensitive family education paradigm, resulted in a lower rate of
      deformity recurrence when treating children with clubfeet using the Ponseti
      method. LEVEL OF EVIDENCE: Level III.

PMID- 23965908
TI  - Osteochondromas after radiation for pediatric malignancies: a role for expanded
      counseling for skeletal side effects.
AB  - BACKGROUND: A relationship has been reported between total body irradiation (TBI)
      and later development of osteochondromas in children who receive radiation
      therapy as conditioning before hematopoietic stem cell transplantation (HSCT).
      The goal of this study was to better characterize osteochondromas occurring in
      these children. METHODS: We identified all children (0 to 18 y) who received an
      allogeneic HSCT and TBI from 2000 to 2012 from a blood and marrow transplant
      (BMT) database. Thereafter, we identified those who developed osteochondromas
      through a chart review. In addition, we searched for diagnosis and operative
      codes from 1996 to 2012 in our pediatric orthopaedic clinical records, isolating
      osteochondroma patients with a history of radiation exposure. RESULTS: Four
      patients who underwent allogeneic HSCT and were later diagnosed with
      osteochondromas were identified from the BMT database (N=233 children); all 4
      were among a group of 72 patients who received TBI. Three patients were
      identified from orthopaedic records. The cohort included 5 boys and 2 girls with
      acute lymphoblastic leukemia (N=5) or neuroblastoma (N=2), diagnosed at a median
      age of 2.0 years. Therapy for all patients included chemotherapy, radiation
      therapy (TBI, N=5; abdominal, N=2), and HSCT. A diagnosis of osteochondroma was
      made at a median age of 11.7 years (range, 5 to 16 y), on average 8.6 years after
      radiation therapy. Diagnosis was incidental in 2 patients and secondary to
      symptoms (pain or genu valgum) in 5. Locations of osteochondromas were the
      proximal tibia (N=3), distal tibia, distal femur, distal ulna, and the distal
      phalanx (N=1 each). Three patients underwent surgical resection. CONCLUSIONS:
      Children may be more likely to develop osteochondromas after early exposure to
      radiation therapy, which may cause pain and require surgical resection. To the
      best of our knowledge, this is the first reported case of a radiation-induced
      osteochondroma causing lower extremity malalignment. Patients typically present
      to the pediatric orthopaedist's attention when symptomatic, but there may be an
      expanded role for counseling for potential for long-term skeletal effects in this
      group. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 23965910
TI  - Distal femoral physeal fixation: are smooth pins really safe?
AB  - BACKGROUND: Distal femoral physeal fractures have a high incidence of physeal
      arrest. Several factors have been postulated to contribute to this high
      incidence, including fracture type, displacement, the undulating nature of the
      physis, and fracture reduction/fixation. The purpose of this study was to
      determine whether the position of percutaneous smooth pins across the physis
      contributes to physeal bar formation. METHODS: The previously validated New
      Zealand white rabbit model was used. Power analysis determined that 30 animals
      were required. All animals had a constant 0.045 smooth Kirschner (K) wire placed
      under fluoroscopic guidance from the distal lateral femur across the physis
      centrally. A second 0.045 K-wire was placed in a cross-pin configuration from the
      medial side in one of 2 positions: zone 1--crossing the physis centrally or zone
      2--crossing the physis peripherally. Pins were removed after 4 weeks and micro
      computed tomography was performed at 8 weeks to assess for physeal bar formation.
      Histologic analysis was performed to confirm bar formation. RESULTS: Two physeal
      bars (7%) were seen after removal of the constant (lateral pin). The peripheral
      pin resulted in bar formation in 2 animals (13%) and the central pin in 1 animal
      (7%). A chi2 test was performed; there was no statistically significant
      difference between zones in terms of bar formation (P=0.5428). CONCLUSIONS:
      Injury to the growth plate after distal femoral fracture may be unavoidable.
      Treatment is aimed to minimize further injury to the physis. Cross-pinning with
      smooth K-wires results in a low rate of physeal injury. Pins that cross the
      physis both centrally and peripherally appear to have the same risk for physeal
      bar formation. CLINICAL RELEVANCE: This study reveals that physeal bar formation
      can be seen with smaller than previously reported cross-sectional damage to the
      distal femoral physis. This study highlights the need to carefully select and
      perform fixation of the distal femoral physis with as little additional trauma to
      the physis as possible.

PMID- 23965912
TI  - Early onset scoliosis: the value of serial risser casts.
AB  - BACKGROUND: Treatment of early onset scoliosis (EOS) is challenging. In many
      cases, bracing will not be effective and growing rod surgery may be
      inappropriate. Serial, Risser casts may be an effective intermediate method of
      treatment. METHODS: We studied 20 consecutive patients with EOS who received
      serial Risser casts under general anesthesia between 1999 and 2011. Analyses
      included diagnosis, sex, age at initial cast application, major curve severity,
      initial curve correction, curve magnitude at the time of treatment change or
      latest follow-up for those still in casts, number of casts per patient, the type
      of subsequent treatment, and any complications. RESULTS: There were 8 patients
      with idiopathic scoliosis, 6 patients with neuromuscular scoliosis, 5 patients
      with syndromic scoliosis, and 1 patient with skeletal dysplasia. Fifteen patients
      were female and 5 were male. The mean age at first cast was 3.8+/-2.3 years
      (range, 1 to 8 y), and the mean major curve magnitude was 74+/-18 degrees (range,
      40 to 118 degrees). After initial cast application, the major curve measured 46+/
      14 degrees (range, 25 to 79 degrees). At treatment change or latest follow-up for
      those still in casts, the major curve measured 53+/-24 degrees (range, 13 to 112
      degrees). The mean time in casts was 16.9+/-9.1 months (range, 4 to 35 mo). The
      mean number of casts per patient was 4.7+/-2.2 casts (range, 1 to 9 casts). At
      the time of this study, 7 patients had undergone growing rod surgery, 6 patients
      were still undergoing casting, 5 returned to bracing, and 2 have been lost to
      follow-up. Four patients had minor complications: 2 patients each with
      superficial skin irritation and cast intolerance. CONCLUSIONS: Serial Risser
      casting is a safe and effective intermediate treatment for EOS. It can stabilize
      relatively large curves in young children and allows the child to reach a more
      suitable age for other forms of treatment, such as growing rods. LEVEL OF
      EVIDENCE: Level IV; case series.

PMID- 23965911
TI  - Long-term patient-reported outcome after fractures of the clavicle in patients
      aged 10 to 18 years.
AB  - BACKGROUND: Fractures of the clavicle are common among adolescents and have
      traditionally been treated nonoperatively. Recent literature has demonstrated
      less satisfactory results than expected after conservative management of
      displaced fractures in adults. The purpose of this study was to evaluate the long
      term patient-reported outcome after clavicle fractures in older children and
      adolescents. METHODS: Children aged 10 to 18 years who sustained a fracture of
      the clavicle between 2006 and 2008 were identified in our institution's
      computerized files. The radiographs were examined and the fracture patterns,
      degree of dislocation, and shortening were measured. Medical records were
      reviewed and the patient-reported outcome was assessed using the Oxford Shoulder
      score and the Quick version of the Disability of Arm, Shoulder, and Hand
      questionnaire, and specific and general satisfaction scores. RESULTS: A total of
      185 patients (median age, 14.4 y) with 172 midshaft and 13 lateral fractures were
      included in the study. Sixty-five (37.8%) of the midshaft fractures were
      displaced, and 9 of these were operated. There was one case of nonunion and one
      delayed union. One hundred twenty-two (70.9%) of the patients with a midshaft
      fracture responded to the questionnaires on an average 4.7 years after injury.
      Overall results were good to excellent for the majority of nonoperatively treated
      patients; however, shortening of the fracture had a negative effect on the Oxford
      Shoulder score (P=0.02), the cosmetic satisfaction score (P=0.02), and the
      overall satisfaction score (P=0.01). CONCLUSIONS: The long-term patient-reported
      outcome after nonoperatively treated fractures of the clavicle in adolescents is
      good to excellent for the majority of the patients, and nonunion is rare.
      However, shortening of the fracture had a small negative effect on the outcome.
      Conservative management should remain the mainstay of management for fractures of
      the clavicle in this age group. LEVEL OF EVIDENCE: Level IV-retrospective case
      series.

PMID- 23965913
TI  - Chronic exertional compartment syndrome of the forearm in adolescents.
AB  - PURPOSE: Chronic exertional compartment syndrome (CECS) is a well-known process,
      although rare in the forearm. The diagnosis is based on history, clinical
      examination, and compartment pressure readings. My objective is to present the
      largest series of CECS of the forearm in adolescents and describe my experience
      in its management and evolution. METHODS: I reviewed 5 patients, 4 male
      (competing in motorcycling or motocross) and 1 female (CECS in both the legs and
      forearms), aged between 15 and 18 years. Volar and dorsal compartments were
      affected in 3 patients and isolated volar in 2 cases. The clinical diagnosis was
      objectively confirmed by measuring ICP with a low-pressure digital transducer
      (Stryker). RESULTS: Open fasciotomy was carried out in 4 patients. They resumed
      their athletic activities 6 weeks after surgery without complications, increasing
      their athletic performance level in line with their preoperative status. All
      these patients remained asymptomatic, recovering their previous competitive
      levels. The results were objectively classified as excellent in all 4 cases.
      After a mean follow-up of 6 years, the condition has not relapsed in any of the
      patients. Two of the patients agreed to a new ICP measurement 1 year after the
      surgery, showing normal values. CONCLUSIONS: CECS in the forearm in adolescents
      is a rare condition that occurs after puberty. A high index of suspicion is
      necessary to diagnose it. It is based on symptoms and ICP measurements. Most
      patients are competing motorcyclists. Surgical treatment, involving isolated
      decompression of the superficial volar compartment, is safe and effective
      (restoring normal ICP).

PMID- 23965914
TI  - Distal humerus atrophic nonunion in a child with osteogenesis imperfecta.
AB  - Atrophic nonunion of the distal humerus in children with osteogenesis imperfecta
      is a vexing and disabling problem. Traditional treatments, including casting,
      intramedullary nailing, plating and bone grafting have not been universally
      successful. We report on a case of successful treatment of one atrophic nonunion
      of the distal humerus in ad 2 year 10 month old child with type III OI who had
      failed more traditional treatments. The treatment used a combination of
      telescoping intramedullary nails, locking plate fixation and bone morphogenic
      protein. LEVEL OF EVIDENCE: Level IV.

PMID- 23965915
TI  - Sitting sagittal balance is different from standing balance in children with
      scoliosis.
AB  - BACKGROUND: Several variables can have effect on sagittal balance. The changes
      that occur between standing and sitting have been inadequately studied,
      especially in the, pediatric population. METHODS: Preoperative sagittal
      radiographs were obtained in both standing and sitting positions for 26 patients
      with idiopathic scoliosis before spinal fusion and instrumentation. Standard
      measurements of thoracic kyphosis, lumbar lordosis, sacral slope (SS), pelvic
      incidence, pelvic tilt, and lumbar intervertebral angles were, recorded.
      Differences were compared between positions using 2-sided paired t tests.
      RESULTS: When moving from standing to a seated position, the spine loses 5-degree
      thoracic kyphosis (P=0.007), 29-degree lumbar lordosis (P<0.0001), and the sacrum
      rotates 20 degrees (P<0.0001) to a more vertical position. The greatest change in
      sitting sagittal balance occurs due to increased pelvic tilt with decreased SS.
      The next greatest change is increased forward flexion of the lowest 2 lumbar
      vertebrae, 6.5 degrees between L4-L5 (P<0.0001) and 5.9 degrees between L5-S1
      (P<0.0001). Flexion occurs throughout the lumbar spine but its magnitude
      decreases in the more proximal lumbar segments, 1.6 degrees between L1-L2
      (P=0.028). The sagittal vertical axis also moves more anterior by 44 mm
      (P<0.0001). CONCLUSIONS: Sitting significantly straightens the spine with
      decreases of thoracic kyphosis, lumbar lordosis, and SS. The majority of the
      changes occur in the lumbar spine and pelvis. As humans spend much of their time
      sitting, this difference should be considered when spinal instrumentation is
      performed. These findings may be important to those who only sit, especially when
      instrumentation is extended to the pelvis. LEVEL OF EVIDENCE: Level II-
      retrospective prognostic study.

PMID- 23965917
TI  - Ulnar nerve monitoring during percutaneous pinning of supracondylar fractures in
      children.
AB  - BACKGROUND: Supracondylar fractures of the humerus in children are frequently
      managed by closed reduction and percutaneous pinning. Insertion of medial and
      lateral pins is more stable than lateral pinning alone, but carries an increased
      risk for ulnar nerve damage. This study describes the use of electrical
      stimulation concurrent with medial pin insertion as a monitoring technique for
      avoiding iatrogenic ulnar nerve injury. METHODS: A retrospective review was
      conducted on 138 children, mean age 5.6 years (SD+/-2.5), who were admitted to
      the hospital between 2007 and 2010 with uncomplicated supracondylar fractures,
      Gartland type II and above, and intact neurovascular presentation. The location
      of the ulnar nerve was identified and marked preoperatively by observing twitch
      contractions in response to electrical stimulation. The medial pin served as an
      active electrode during pin insertion, and repeated stimulation throughout the
      insertion process ensured no contact with the response of the ulnar nerve. After
      pin insertion, ulnar nerve stimulation was used again to ensure nerve continuity
      viability. RESULTS: All fractures were stabilized with 2 to 4 cross K-wires (size
      1.6 mm), with number depending on stability of the fracture. The children were
      discharged home 2 days after fracture fixation, with no iatrogenic ulnar nerve
      injury observed in any of the children. The only postoperative complication
      involved 2 cases of anterior interosseus nerve neuropraxia, which resolved
      spontaneously after 4 to 6 months. Primary fracture healing was achieved without
      nonunions or delayed unions in all cases. CONCLUSIONS: Ulnar nerve stimulation
      before and during the percutaneous pinning of supracondylar fractures in children
      is a simple, economical, and easy-to-implement technique that can prevent
      iatrogenic ulnar nerve injury. LEVEL OF EVIDENCE: Level IV.

PMID- 23965916
TI  - Correction of lower extremity angular deformities in skeletal dysplasia with
      hemiepiphysiodesis: a preliminary report.
AB  - BACKGROUND: Lower extremity angular deformities are common in children with
      skeletal dysplasia and can be treated with various surgical options. Both acute
      correction by osteotomy with internal fixation and gradual correction by external
      fixation have been used with acceptable results. Recently, the Guided Growth
      concept using temporary hemiepiphysiodesis for correction of angular deformities
      in the growing child has been proposed. This study presents the results of
      temporary hemiepiphysiodesis using eight-Plates and medial malleolus transphyseal
      screws in children with skeletal dysplasia with lower extremity angular
      deformities. METHODS: Twenty-nine patients (50 lower extremities) with skeletal
      dysplasia of different types were treated for varus or valgus deformities at 2
      centers. The mean age at the time of hemiepiphysiodesis was 10+/-2.9 years. A
      total of 66 eight-Plates and 12 medial malleolus screws were used. The average
      follow-up time between the index surgery and the latest follow-up with the eight
      Plate in was 25+/-13.4 months. Erect long-standing anteroposterior and lateral
      view radiographs were obtained for deformity planning before the procedure.
      Angular deformities on radiograph were evaluated by mechanical axis deviation,
      mechanical lateral distal femoral angle, medial proximal tibial angle, and
      lateral distal tibial angle. Mechanical axis deviation was also expressed as a
      percentage to one half of the width of the tibial plateau, and the magnitude of
      the deformity was classified by determining the zones through which the
      mechanical axis of the lower extremity passed. Four zones were determined on both
      the medial and lateral side of the knee and the zones were labeled 1, 2, 3, and
      4, corresponding to the severity of the deformity. A positive value was assigned
      for valgus alignment and a negative for varus alignment. RESULTS: Patients were
      analyzed in valgus and varus groups. There was correction in 34 of 38 valgus legs
      and 7 of 12 varus legs. In the valgus group, the mean preoperative and
      postoperative mechanical lateral distal femoral angles were 82.1+/-3.7 and 91.1+/
      4.9 degrees, respectively (P<0.001). The mean preoperative and postoperative
      medial proximal tibial angles were 98.5+/-8 and 87.8+/-7.1 degrees, respectively
      (P<0.001). Six patients with bilateral ankle valgus deformities (12 ankles)
      underwent single-screw medial malleolus hemiepiphysiodesis. The mean preoperative
      and postoperative lateral distal tibial angles were 73.9+/-8.7 and 86.1+/-6.8
      degrees, respectively (P<0.001). The numbers of plates in each anatomic location
      were not enough to make statistical conclusions in varus legs. Four patients in
      the valgus group and 3 patients in the varus group did not benefit from the
      procedure. Mechanical axes were in zone 2 or over in 94% of the legs
      preoperatively, whereas postoperatively, only 23% of the legs had mechanical axes
      in zone 2 or over in varus and valgus groups. CONCLUSIONS: Growth modulation with
      an eight-Plate is a relatively simple surgery and has low risk of mechanical
      failure or physeal damage. It can be performed in very young patients, which is
      an important advantage in skeletal dysplasia. Screw purchase is reliable even in
      the abnormal epiphysis and metaphysis. Our results show that Guided Growth using
      eight-Plates in skeletal dysplasia is safe and effective. LEVEL OF EVIDENCE:
      Level IV.

PMID- 23965918
TI  - The advantage of reversible coordination polymers in producing visible light
      sensitized Eu(III) emissions over EDTA via excluding water from the coordination
      sphere.
AB  - In this paper, we report on the impact of the structure of ligands on the
      luminescence enhancement of Eu(III) by directly exciting Eu(III) with visible
      light in aqueous media. Upon replacing the water molecules that coordinated
      around a Eu(3+) ion with a ditopic ligand 1,11-bis(2,6-dicarboxypyridin-4-yloxy)
      3,6,9-trioxaundecane (L2EO4) or ethylenediaminetetraacetic acid disodium salt
      (EDTA), significant luminescence can be obtained. L2EO4 may occupy all 9
      coordinating sites of a Eu(3+) ion at proper L2EO4/Eu ratios, whereas EDTA only
      occupies 6 of them with 3 sites left for water at various EDTA/Eu ratios. These
      coordinated water molecules quench the fluorescence of EDTA-Eu complexes
      drastically so that the luminescence is about 30 times lower than that of the
      L2EO4-Eu system. Furthermore, the negatively charged L2EO4/Eu = 3/2 coordinated
      complex can be further transformed into coordination 'polymers' by mixing with a
      positively charged block polyelectrolyte, which forms electrostatic micelles with
      further enhanced luminescence. The emission of the EDTA-Eu complex is not
      influenced by the addition of polymers due to the formation of stable small 1 : 1
      EDTA-Eu complex which doesn't change with increasing concentration. Our work
      points out that the L2EO4-Eu system is superior to the EDTA-Eu system in creating
      visible light sensitized Eu(III) luminescence, and the emission of Eu(III) can be
      indeed significantly enhanced to an applicable level by excluding all the water
      molecules in the coordination sphere of Eu(III).

PMID- 23965919
TI  - Parental inflammatory bowel disease and risk of asthma in offspring: a nationwide
      cohort study in denmark.
AB  - OBJECTIVES: Common genetic and environmental risk factors may explain the
      concurrent increase in the incidence of both inflammatory bowel disease (IBD) and
      asthma. We examined whether IBD in a parent is associated with an increased
      asthma risk in offspring. METHODS: This was a registry-based cohort study of all
      children born alive in Denmark in 1979-2009, followed through 2010. IBD and
      asthma were identified using hospital diagnoses; antiasthma medication was also
      used to identify asthma. We computed risk of asthma and estimated adjusted
      incidence rate ratios (aIRRs) with 95% confidence intervals (CIs) using Cox
      proportional-hazards regression. We evaluated asthma risk according to maternal
      and paternal IBD, Crohn's disease (CD), and ulcerative colitis (UC). Children
      without parental IBD were the comparison cohort for all comparisons. RESULTS: We
      identified 1,845,281 children, of whom 14,952 (0.8%) had a parent with IBD. The
      10-year risk of asthma was 6.9% among offspring of parents with CD, 5.6% among
      offspring of parents with UC, and 5.0% among offspring of parents without IBD.
      The aIRR for asthma associated with parental IBD was 0.98 (95% CI: 0.91-1.04).
      The aIRR was 1.09 (95% CI: 0.98-1.22) for parental CD and 0.92 (95% CI: 0.84
      1.00) for parental UC. Results were similar regardless of parent of origin or
      inclusion of antiasthma medication to define asthma. CONCLUSIONS: Our data do not
      provide evidence for an increased risk of asthma in offspring with a parental
      history of IBD.

PMID- 23965920
TI  - Biphasic myosin II light chain activation during clot retraction.
AB  - Clot retraction is an essential step during primary haemostasis, thereby
      promoting thrombus stability and wound healing. Integrin alphaIIbbeta3 plays a
      critical role in clot retraction, by inducing acto-myosin interactions that allow
      platelet cytoskeleton reorganisation. However, the signalling pathways that lead
      to clot retraction are still misunderstood. In this study, we report the first
      data on the kinetics of myosin II light chain (MLC) phosphorylation during clot
      retraction. We found an early phosphorylation peak followed by a second peak. By
      using specific inhibitors of kinases and small G proteins, we showed that MLC
      kinase (MLCK), RhoA/ROCK, and Rac-1 were involved in clot retraction and in the
      early MLC phosphorylation peak. Only Rac-1 and actin polymerisation, controlled
      by outside-in signalling, were crucial to the second MLC phosphorylation peak. 

PMID- 23965921
TI  - Arsenic resistance and prevalence of arsenic resistance genes in Campylobacter
      jejuni and Campylobacter coli isolated from retail meats.
AB  - Studies that investigate arsenic resistance in the foodborne bacterium
      Campylobacter are limited. A total of 552 Campylobacter isolates (281
      Campylobacter jejuni and 271 Campylobacter coli) isolated from retail meat
      samples were subjected to arsenic resistance profiling using the following
      arsenic compounds: arsanilic acid (4-2,048 MUg/mL), roxarsone (4-2048 MUg/mL),
      arsenate (16-8,192 MUg/mL) and arsenite (4-2,048 MUg/mL). A total of 223 of these
      isolates (114 Campylobacter jejuni and 109 Campylobacter coli) were further
      analyzed for the presence of five arsenic resistance genes (arsP, arsR, arsC,
      acr3, and arsB) by PCR. Most of the 552 Campylobacter isolates were able to
      survive at higher concentrations of arsanilic acid (512-2,048 MUg/mL), roxarsone
      (512-2,048 MUg/mL), and arsenate (128-1,024 MUg/mL), but at lower concentrations
      for arsenite (4-16 MUg/mL). Ninety seven percent of the isolates tested by PCR
      showed the presence of arsP and arsR genes. While 95% of the Campylobacter coli
      isolates contained a larger arsenic resistance operon that has all of the four
      genes (arsP, arsR, arsC and acr3), 85% of the Campylobacter jejuni isolates
      carried the short operon (arsP, and arsR). The presence of arsC and acr3 did not
      significantly increase arsenic resistance with the exception of conferring
      resistance to higher concentrations of arsenate to some Campylobacter isolates.
      arsB was prevalent in 98% of the tested Campylobacter jejuni isolates, regardless
      of the presence or absence of arsC and acr3, but was completely absent in
      Campylobacter coli. To our knowledge, this is the first study to determine
      arsenic resistance and the prevalence of arsenic resistance genes in such a large
      number of Campylobacter isolates. 

PMID- 23965922
TI  - Insights from parents about caring for a child with birth defects.
AB  - Birth defects affect 1 in 33 babies. Having a child with a birth defect impacts
      the whole family. Parents of children who have birth defects face unique
      challenges and desire to make life better for their kids. They also want to help
      to prevent birth defects in the future. Some of the challenges parents face
      involve communication with healthcare professionals, quality of life issues,
      creating awareness and advocating for research and funding, finding resources and
      support, and helping teens transition to appropriate, specialized adult care.
      This paper addresses these issues and their sub-issues, provides examples, and
      makes suggestions for improvement and research. 

PMID- 23965923
TI  - Communication by mothers with breast cancer or melanoma with their children.
AB  - Communication of familial risk of breast cancer and melanoma has the potential to
      educate relatives about their risk, and may also motivate them to engage in
      prevention and early detection practices. With the Health Insurance Portability
      and Accountability Act (HIPAA) privacy laws, the patient often becomes the sole
      communicator of such risks to family members. This study surveys mothers
      diagnosed with either breast cancer or melanoma and their adult children about
      their family communication style, knowledge of increased risk, and early
      detection practices. In both cancer groups, most mothers alerted their children
      of the risk and need for early detection practices. Breast cancer mothers
      communicated risk and secondary prevention with early detection by breast self
      examination and mammograms whereas the melanoma mothers communicated risk and
      primary prevention strategies like applying sunscreen and avoiding deliberate
      tanning. Open communication about health matters significantly increased the
      likelihood that children engaged in early detection and/or primary prevention
      behaviors. Examining the information conveyed to at-risk family members, and
      whether such information motivated them to engage in early detection/prevention
      behaviors, is key to guiding better cancer prevention communication between
      doctors and patients. 

PMID- 23965924
TI  - Reporting of foodborne illness by U.S. consumers and healthcare professionals.
AB  - During 2009-2010, a total of 1,527 foodborne disease outbreaks were reported by
      the Centers for Disease Control and Prevention (CDC) (2013). However, in a 2011
      CDC report, Scallan et al. estimated about 48 million people contract a foodborne
      illness annually in the United States. Public health officials are concerned with
      this under-reporting; thus, the purpose of this study was to identify why
      consumers and healthcare professionals don't report foodborne illness. Focus
      groups were conducted with 35 consumers who reported a previous experience with
      foodborne illness and with 16 healthcare professionals. Also, interviews with
      other healthcare professionals with responsibility of diagnosing foodborne
      illness were conducted. Not knowing who to contact, being too ill, being unsure
      of the cause, and believing reporting would not be beneficial were all identified
      by consumers as reasons for not reporting foodborne illness. Healthcare
      professionals that participated in the focus groups indicated the amount of time
      between patients' consumption of food and seeking treatment and lack of knowledge
      were barriers to diagnosing foodborne illness. Issues related to stool samples
      such as knowledge, access and cost were noted by both groups. Results suggest
      that barriers identified could be overcome with targeted education and improved
      access and information about the reporting process. 

PMID- 23965925
TI  - Infertility and its treatments in association with autism spectrum disorders: a
      review and results from the CHARGE study.
AB  - Previous findings on relationships between infertility, infertility therapies,
      and autism spectrum disorders (ASD) have been inconsistent. The goals of this
      study are first, to briefly review this evidence and second, to examine
      infertility and its treatments in association with having a child with ASD in
      newly analyzed data. In review, we identified 14 studies published as of May 2013
      investigating infertility and/or its treatments and ASD. Overall, prior results
      showed little support for a strong association, though some increases in risk
      with specific treatments were found; many limitations were noted. In new analyses
      of the CHildhood Autism Risk from Genetics and the Environment (CHARGE)
      population-based study, cases with autism spectrum disorder (ASD, n = 513) and
      controls confirmed to have typical development (n = 388) were compared with
      regard to frequencies of infertility diagnoses and treatments overall and by
      type. Infertility diagnoses and treatments were also grouped to explore potential
      underlying pathways. Logistic regression was used to obtain crude and adjusted
      odds ratios overall and, in secondary analyses, stratified by maternal age (>=35
      years) and diagnostic subgroups. No differences in infertility, infertility
      treatments, or hypothesized underlying pathways were found between cases and
      controls in crude or adjusted analyses. Numbers were small for rarer therapies
      and in subgroup analyses; thus the potential for modest associations in specific
      subsets cannot be ruled out. However, converging evidence from this and other
      studies suggests that assisted reproductive technology is not a strong
      independent risk factor for ASD. Recommendations for future studies of this topic
      are provided. 

PMID- 23965926
TI  - The role of Australian mosquito species in the transmission of endemic and exotic
      West Nile virus strains.
AB  - Recent epidemic activity and its introduction into the Western Hemisphere have
      drawn attention to West Nile virus (WNV) as an international public health
      problem. Of particular concern has been the ability for the virus to cause
      outbreaks of disease in highly populated urban centers. Incrimination of
      Australian mosquito species is an essential component in determining the
      receptivity of Australia to the introduction and/or establishment of an exotic
      strain of WNV and can guide potential management strategies. Based on vector
      competence experiments and ecological studies, we suggest candidate Australian
      mosquito species that would most likely be involved in urban transmission of WNV,
      along with consideration of the endemic WNV subtype, Kunjin. We then examine the
      interaction of entomological factors with virological and vertebrate host
      factors, as well as likely mode of introduction, which may influence the
      potential for exotic WNV to become established and be maintained in urban
      transmission cycles in Australia. 

PMID- 23965927
TI  - The contribution of childhood parental rejection and early androgen exposure to
      impairments in socio-cognitive skills in intimate partner violence perpetrators
      with high alcohol consumption.
AB  - Alcohol consumption, a larger history of childhood parental rejection, and high
      prenatal androgen exposure have been linked with facilitation and high risk of
      recidivism in intimate partner violence (IPV) perpetrators. Participants were
      distributed into two groups according to their alcohol consumption scores as high
      (HA) and low (LA). HA presented a higher history of childhood parental rejection,
      prenatal masculinization (smaller 2D:4D ratio), and violence-related scores than
      LA IPV perpetrators. Nonetheless, the former showed poor socio-cognitive skills
      performance (cognitive flexibility, emotional recognition and cognitive empathy).
      Particularly in HA IPV perpetrators, the history of childhood parental rejection
      was associated with high hostile sexism and low cognitive empathy. Moreover, a
      masculinized 2D:4D ratio was associated with high anger expression and low
      cognitive empathy. Parental rejection during childhood and early androgen
      exposure are relevant factors for the development of violence and the lack of
      adequate empathy in adulthood. Furthermore, alcohol abuse plays a key role in the
      development of socio-cognitive impairments and in the proneness to violence and
      its recidivism. These findings contribute to new coadjutant violence intervention
      programs, focused on the rehabilitation of basic executive functions and
      emotional decoding processes and on the treatment of alcohol dependence. 

PMID- 23965930
TI  - A novel molecular index for secondary oil migration distance.
AB  - Determining oil migration distances from source rocks to reservoirs can greatly
      help in the search for new petroleum accumulations. Concentrations and ratios of
      polar organic compounds are known to change due to preferential sorption of these
      compounds in migrating oils onto immobile mineral surfaces. However, these
      compounds cannot be directly used as proxies for oil migration distances because
      of the influence of source variability. Here we show that for each source facies,
      the ratio of the concentration of a select polar organic compound to its initial
      concentration at a reference point is independent of source variability and
      correlates solely with migration distance from source rock to reservoir. Case
      studies serve to demonstrate that this new index provides a valid solution for
      determining source-reservoir distance and could lead to many applications in
      fundamental and applied petroleum geoscience studies. 

PMID- 23965928
TI  - Thimerosal exposure and the role of sulfation chemistry and thiol availability in
      autism.
AB  - Autism spectrum disorder (ASD) is a neurological disorder in which a significant
      number of the children experience a developmental regression characterized by a
      loss of previously acquired skills and abilities. Typically reported are losses
      of verbal, nonverbal, and social abilities. Several recent studies suggest that
      children diagnosed with an ASD have abnormal sulfation chemistry, limited thiol
      availability, and decreased glutathione (GSH) reserve capacity, resulting in a
      compromised oxidation/reduction (redox) and detoxification capacity. Research
      indicates that the availability of thiols, particularly GSH, can influence the
      effects of thimerosal (TM) and other mercury (Hg) compounds. TM is an
      organomercurial compound (49.55% Hg by weight) that has been, and continues to
      be, used as a preservative in many childhood vaccines, particularly in developing
      countries. Thiol-modulating mechanisms affecting the cytotoxicity of TM have been
      identified. Importantly, the emergence of ASD symptoms post-6 months of age
      temporally follows the administration of many childhood vaccines. The purpose of
      the present critical review is provide mechanistic insight regarding how limited
      thiol availability, abnormal sulfation chemistry, and decreased GSH reserve
      capacity in children with an ASD could make them more susceptible to the toxic
      effects of TM routinely administered as part of mandated childhood immunization
      schedules. 

PMID- 23965929
TI  - MG53-induced IRS-1 ubiquitination negatively regulates skeletal myogenesis and
      insulin signalling.
AB  - Mitsugumin 53 (MG53) negatively regulates skeletal myogenesis by targeting
      insulin receptor substrate 1 (IRS-1). Here, we show that MG53 is an ubiquitin E3
      ligase that induces IRS-1 ubiquitination with the help of an E2-conjugating
      enzyme, UBE2H. Molecular manipulations that disrupt the E3-ligase function of
      MG53 abolish IRS-1 ubiquitination and enhance skeletal myogenesis. Skeletal
      muscles derived from the MG53-/- mice show an elevated IRS-1 level with enhanced
      insulin signalling, which protects the MG53-/- mice from developing insulin
      resistance when challenged with a high-fat/high-sucrose diet. Muscle samples
      derived from human diabetic patients and mice with insulin resistance show normal
      expression of MG53, indicating that altered MG53 expression does not serve as a
      causative factor for the development of metabolic disorders. Thus, therapeutic
      interventions that target the interaction between MG53 and IRS-1 may be a novel
      approach for the treatment of metabolic diseases that are associated with insulin
      resistance.

PMID- 23965932
TI  - Shaping medicinal product information: a before and after study exploring
      physicians' perspectives on the summary of product characteristics.
AB  - OBJECTIVE: To establish, in the context of the revised European Pharmacovigilance
      Directive and based on physicians' perspectives, how Summaries of Product
      Characteristics (SmPCs) could be more user friendly and better support
      physicians' interactions with patients, thereby improving patients' own
      understanding of their medicines. DESIGN: Qualitative focus group discussions
      (step 1), development of an alternative SmPC (step 2) and an online quantitative
      survey (step 3) comparing the alternative SmPC to the currently approved version.
      SETTING: Office-based physicians (n=218) from all federal states of Germany.
      PARTICIPANTS: 218 German physicians participated, with an equal representation of
      office-based general practitioners and specialists. For step 1 (n=18), physicians
      were recruited who frequently consulted SmPCs. OUTCOME MEASURES: Planned and
      performed: Mayring's qualitative content analysis of focus group discussions
      (step 1), rating on a five-point Likert scale of preference of current versus
      alternative SmPCs (step 3). RESULTS: Physicians confirmed the importance of SmPCs
      as a comprehensive source of medicinal product information, but were moderately
      satisfied with the current SmPCs, utilised it infrequently and were more likely
      to engage additional sources of information. The alternative SmPC was
      consistently preferred. It differed in the way information for particular patient
      groups was presented, included additional sections (synopsis, checklist for
      patient information) and used a tabular format. Physicians indicated that SmPCs
      should be available with search and hyperlink functions, as well as be
      automatically updated and integrated in available practice software or similar
      solutions. CONCLUSIONS: This research contributes to the development of an
      official, reliable medicinal product information system meeting the needs of a
      modern information society while providing the reliability of an officially
      authorised source. In the context of health literacy, SmPCs should be established
      as the primary information source for healthcare professionals to ensure
      compliant and safe utilisation of medicinal products.

PMID- 23965931
TI  - How active are our children? Findings from the Millennium Cohort Study.
AB  - OBJECTIVE: To describe levels of physical activity, sedentary time and adherence
      to Chief Medical Officers (CMO) physical activity guidelines among primary school
      aged children across the UK using objective accelerometer-based measurements.
      DESIGN: Nationally representative prospective cohort study. SETTING: Children
      born across the UK, between 2000 and 2002. PARTICIPANTS: 6497 7-year-old to 8
      year-old singleton children for whom reliable accelerometer data were available
      for at least 10 h a day for at least 2 days. MAIN OUTCOME MEASURES: Physical
      activity in counts per minute (cpm); time spent in sedentary and moderate-to
      vigorous intensity physical activity (MVPA); proportion of children meeting CMO
      guidelines (>=60 min/day MVPA); average daily steps. EXPLANATORY MEASURES:
      Gender, ethnicity, maternal current/most recent occupation, lone parenthood
      status, number of children in the household and country/region of residence.
      RESULTS: The median daily physical activity level was 595 cpm (IQR 507, 697).
      Children spent a median of 60 min (IQR 47-76) in MVPA/day and were sedentary for
      a median of 6.4 h/day (IQR 6-7). Only 51% met CMO guidelines, with girls (38%)
      less active than boys (63%). Children took an average of 10 229 (95% CI (8777 to
      11 775)) steps each day. Children of Indian ethnicity were significantly less
      active overall than all other ethnic groups. Children of Bangladeshi origin and
      those living in Northern Ireland were least likely to meet CMO guidelines.
      CONCLUSIONS: Only half of 7-year-old children in the UK achieve recommended
      levels of physical activity, with significant gender, ethnic and geographic
      variations. Longitudinal studies are needed to better understand the relevance of
      these (in)activity patterns for long-term health and well-being. In the meantime
      population-wide efforts to boost physical activity among young people are needed
      which are likely to require a broad range of policy interventions.

PMID- 23965933
TI  - Correction.

PMID- 23965934
TI  - Extending the use of PROMs in the NHS--using the Oxford Knee Score in patients
      undergoing non-operative management for knee osteoarthritis: a validation study.
AB  - OBJECTIVES: To assess the validity of the Oxford Knee Score (OKS) for use in
      patients undergoing non-operative management for their knee osteoarthritis (OA)
      within the National Health Service (NHS). DESIGN: Observational cohort study.
      SETTING: Single orthopaedic centre in England. PARTICIPANTS: 134 patients
      undergoing non-operative management for knee OA. MAIN OUTCOME MEASURES: OKS, the
      Intermittent and Constant Osteoarthritis Pain (ICOAP), the Knee Injury and
      Osteoarthritis Score-Physical Function Short Form (KOOS-PS), at baseline and 3
      month follow-up, transition item of change at 3 months. RESULTS: The OKS summary
      scale and its pain and functional component subscales demonstrated good test
      retest reliability (intraclass correlation coefficient 0.93, 0.91 and 0.92,
      respectively) and measurement precision which, allows its use with groups of
      patients with knee OA (research/audit) and with individuals (clinical practice).
      The results in this study were consistent with a priori set hypotheses about the
      relationship of OKS with other validated measures (KOOS-PS, ICOAP and short form
      12 (SF-12)), which provided evidence of its construct validity and
      responsiveness. Confirmatory factor analysis confirmed the structural validity of
      OKS. However, there was a lack of satisfactory evidence of structural validity
      for ICOAP and KOOS. The minimum detectable change (MDC90) was +/-6 for OKS (+/-16
      for the Pain Component Score (OKS-PCS) and +/-15 for the Functional Component
      Score (OKS-FCS)). Minimal important changes were ~7 for OKS (~17 for OKS-PCS and
      ~11 for OKS-FCS) and minimal important differences were ~6 for OKS (~14 for OKS
      PCS and ~10 for OKS-FCS). These values were also calculated for ICOAP and KOOS
      PS. CONCLUSIONS: The OKS summary scale, together with its pain and functional
      component subscales, has excellent measurement properties when used with patients
      with knee OA undergoing non-operative treatment and is superior to ICOAP and KOOS
      PS for this purpose. This evidence provides support for the validity of the use
      of OKS when used across the spectrum of knee OA disease severity, both in
      research and clinical practice.

PMID- 23965935
TI  - Does comorbidity increase the risk of mortality among children under 3 years of
      age?
AB  - OBJECTIVES: Diarrhoea and pneumonia remain leading causes of morbidity and
      mortality in children under 5 years of age. Little data is available to quantify
      the burden of comorbidity and the relationship between comorbid diarrhoea and
      pneumonia infections and mortality. We sought to quantify the relationship
      between comorbidity and risk of mortality among young children in two community
      based studies conducted among South Asian children. DESIGN: Secondary data
      analysis of two cohort studies. PARTICIPANTS: We identified two cohort studies of
      children under 3 years of age with prospective morbidity at least once every 2
      weeks and ongoing mortality surveillance. OUTCOME MEASURES: We calculated the
      mortality risk for diarrhoea and acute lower respiratory infection (ALRI)
      episodes and further quantified the risk of mortality when both diseases occur at
      the same time using a semiparametric additive model. RESULTS: Among Nepali
      children, the estimated additional risk of mortality for comorbid diarrhoea and
      ALRI was 0.0014 (-0.0033, 0.0060). Among South Indian children, the estimated
      additional risk of mortality for comorbid diarrhoea and ALRI was 0.0032 (-0.0098,
      0.0162). This risk is in addition to the single infection risk of mortality
      observed among these children. CONCLUSIONS: We observed an additional risk of
      mortality in children who experienced simultaneous diarrhoea and ALRI episodes
      though the CI was wide indicating low statistical support. Additional studies
      with adequate power to detect the increased risk of comorbidity on mortality are
      needed to improve confidence around the effect size estimate.

PMID- 23965937
TI  - Dental trauma on ski slopes.
AB  - OBJECTIVES: Skiing and snow-boarding are winter sports with risk of dental
      trauma. The aim of the present study was to investigate the use of protective
      gear and the occurrence of dental trauma in amateur winter sports on ski slopes.
      MATERIALS AND METHODS: A total of 500 skiers and snowboarders (345 skiers, 110
      snow-boarders, and 45 who rode both) were interviewed using a standardized
      questionnaire during one winter season (from January to April 2008). Sustained
      injuries and use of protective gear (including mouthguards) were assessed.
      RESULTS: Of the 500 interviewed, eleven (9 m, 2 f; 2.2%) had sustained dental
      trauma while skiing or snowboarding. Frequent riders were most susceptible to
      dental trauma (p < 0.001). 165 (33%) have sustained a skiing or snow- boarding
      accident at least once, males more often than females (p = 0.031). Protective
      gear was used by 337 (67.4%), helmet, back and wrist protectors being worn most
      often. Snow-boarders were generally protected best (p < 0.001). All riders who
      had sustained an accident (n = 124; 75.1%) wore protective gear at the time of
      the interview (p = 0.009). Only two of eleven who had sustained dental trauma
      wear a mouthguard now for winter sports. CONCLUSION: The results show that skiing
      and snowboarding pose only a small risk for dental trauma.

PMID- 23965936
TI  - Reducing risk with e-based support for adherence to lifestyle change in
      hypertension (REACH): protocol for a multicentred randomised controlled trial.
AB  - INTRODUCTION: Web-based lifestyle counselling designed to improve adherence to
      self-management behaviours for diet, exercise and medication has been shown to
      reduce blood pressure (BP). However, the long-term clinical outcome of these
      interventions is not established. Our aim was to establish whether an e
      counselling program is independently associated with improved clinical outcomes
      over a 12-month period, as defined by the following criteria: (1) reduction of
      systolic BP, diastolic BP, pulse pressure and associated risk factors for
      cardiovascular events; and (2) adherence to self-management behaviour (diet,
      exercise, smoke-free living and prescribed medication). METHODS AND ANALYSIS:
      Reducing risk with e-based support for adherence to lifestyle change in
      hypertension is a two-parallel group, double-blind randomised controlled trial
      that will utilise a two (Groups: e-counselling vs control) by three (assessment
      intervals: baseline, 4-month and 12-month outcome) design. BP, lipoprotein
      cholesterol, physical activity and dietary behaviours and psychological distress
      will be measured at each assessment. We plan to recruit 528 participants (35-74
      years of age) diagnosed with stage 1 or 2 hypertension (systolic BP, 140-180 mm
      Hg; diastolic BP 90-110 mm Hg) from three major cities (Toronto, London,
      Vancouver) and one rural area (Grey Bruce region) across Canada between February
      2012 and July 2015. Controls will receive general educational e-messages on heart
      healthy living and the e-counselling group will receive tailored e-messages that
      are matched to their stage of readiness for change. For both groups, e-messages
      will be sent proactively on a weekly basis during months 1-4, then bi-weekly
      during months 5-8 and then monthly during months 9-12. ETHICS AND DISSEMINATION:
      Ethical approval has been obtained from all recruitment sites. This will be one
      of the first studies to evaluate the long-term efficacy of preventive e
      counselling strategies for cardiovascular disease prevention in patients with
      hypertension. Findings from this study will be used to guide the ongoing
      development of e-counselling services. TRIAL REGISTRATION: Clinicaltrial.gov
      NCT01541540; http://clinicaltrials.gov/ct2/show/NCT01541540.

PMID- 23965938
TI  - Microsporidial keratoconjunctivitis after rugby tournament, Singapore.
AB  - We investigated an outbreak of 47 probable and 6 confirmed cases of
      microsporidial keratoconjunctivitis involving participants of an international
      rugby tournament in Singapore in April 2012.The mode of transmission was eye
      contact with soil. Vittaforma corneae was identified in 4 of 6 corneal scrapings
      and in 1 of 12 soil water samples. 

PMID- 23965939
TI  - A simplified analytical dose calculation algorithm accounting for tissue
      heterogeneity for low-energy brachytherapy sources.
AB  - The American Association of Physicists in Medicine Task Group No. 43 (AAPM TG-43)
      formalism is the standard for seeds brachytherapy dose calculation. But for
      breast seed implants, Monte Carlo simulations reveal large errors due to tissue
      heterogeneity. Since TG-43 includes several factors to account for source
      geometry, anisotropy and strength, we propose an additional correction factor,
      called the inhomogeneity correction factor (ICF), accounting for tissue
      heterogeneity for Pd-103 brachytherapy. This correction factor is calculated as a
      function of the media linear attenuation coefficient and mass energy absorption
      coefficient, and it is independent of the source internal structure. Ultimately
      the dose in heterogeneous media can be calculated as a product of dose in water
      as calculated by TG-43 protocol times the ICF. To validate the ICF methodology,
      dose absorbed in spherical phantoms with large tissue heterogeneities was
      compared using the TG-43 formalism corrected for heterogeneity versus Monte Carlo
      simulations. The agreement between Monte Carlo simulations and the ICF method
      remained within 5% in soft tissues up to several centimeters from a Pd-103
      source. Compared to Monte Carlo, the ICF methods can easily be integrated into a
      clinical treatment planning system and it does not require the detailed internal
      structure of the source or the photon phase-space. 

PMID- 23965940
TI  - Characterization of Eimeria brunetti Isolated from a Poultry Farm in Japan.
AB  - None of anticoccidial vaccines (Trivalent TAMTM, monovalent NecaTM and imported
      pentavalent Paracox((r))-5) contain Eimeria brunetti in Japan, which has not been
      regarded as a cause of coccidiosis, because of its low prevalence. However, we
      have recently reported the evidence of a high nationwide prevalence of this
      species. In this report, we describe the characteristics of E. brunetti which
      have never been clearly defined in Japan. Mortality rates and other disease
      characteristics caused by our strain (Nb strain) were similar to those reported
      previously in other studies. Despite great reduction of body weight gains among
      groups infected with over 1 * 10(3) oocysts, the intestinal lesions in the
      infected chickens were rather mild compared to previous studies. Sulfa drugs and
      lasalocid were so effective that the E. brunetti infection was almost completely
      blocked. Consequently, it is suggested that the characteristics of E. brunetti
      are various among the strains, but the pathogenicity of the Japanese Nb strain is
      enough strong to cause clinical coccidiosis. 

PMID- 23965941
TI  - Procoagulant reactivity to laboratory acute mental stress in Africans and
      Caucasians, and its relation to depressive symptoms: the SABPA study.
AB  - The risk of cardiovascular disease is dramatically increasing in Africans
      (black). The prothrombotic stress response contributes to atherothrombotic
      disease and is modulated by depressive symptoms. We examined coagulation
      reactivity to acute mental stress and its relation to psychological well-being in
      Africans relative to Caucasians (white). A total of 102 African and 165 Caucasian
      school teachers underwent the Stroop Color-Word Conflict test. Circulating levels
      of von Willebrand factor (VWF) antigen, fibrinogen, and D-dimer were measured
      before and after the Stroop. Cardiovascular reactivity measures were also
      obtained. All participants completed the Patient Health Questionnaire-9 and the
      General Health Questionnaire-28 for the assessment of depressive symptoms and
      total psychological distress, respectively. After controlling for covariates,
      resting levels of VWF, fibrinogen, and D-dimer were higher in Africans than in
      Caucasians (all p-values <=0.006). Depressive symptoms and psychological distress
      were not significantly associated with resting coagulation measures. Stress
      reactivity in VWF (p<0.001) and fibrinogen (p=0.016), but not in D-dimer
      (p=0.27), were decreased in Africans relative to Caucasians with Africans showing
      greater reactivity of total peripheral resistance (p=0.017). Depressive symptoms,
      but not general psychological distress, were associated with greater VWF increase
      (p=0.029) and greater fibrinogen decrease (p=0.030) in Africans relative to
      Caucasians. In conclusion, Africans showed greater hypercoagulability at rest but
      diminished procoagulant reactivity to acute mental stress when compared with
      Caucasians. Ethnic differences in the vascular adrenergic stress response might
      partially explain this finding. Depressive symptoms were associated with
      exaggerated VWF reactivity in Africans relative to Caucasians. The clinical
      implications of these findings for Africans need further study. 

PMID- 23965942
TI  - Genetic variation near IRF8 is associated with serologic and cytokine profiles in
      systemic lupus erythematosus and multiple sclerosis.
AB  - Alleles of interferon (IFN) regulatory factor 8 (IRF8) are associated with
      susceptibility to both systemic lupus erythematosus (SLE) and multiple sclerosis
      (MS). Although high-type I IFN is thought to be causal in SLE, type I IFN is used
      as a therapy in MS. We investigated whether IRF8 alleles were associated with
      type I IFN levels or serologic profiles in SLE and MS. Alleles that have been
      previously associated with SLE or MS were genotyped in SLE and MS patients. The
      MS-associated rs17445836G allele was associated with anti-double-stranded DNA
      (dsDNA) autoantibodies in SLE patients (meta-analysis odds ratio=1.92). The same
      allele was associated with decreased serum IFN activity in SLE patients with anti
      dsDNA antibodies, and with decreased type I IFN-induced gene expression in
      peripheral blood mononuclear cell from anti-dsDNA-negative SLE patients. In
      secondary progressive MS patients, rs17445836G was associated with decreased
      serum type I IFN. Rs17445836G was associated with increased IRF8 expression in
      SLE patient B cells. In summary, IRF8 rs17445836G is associated with human
      autoimmune disease characterized by low-type I IFN levels, and this may have
      pharmacogenetic relevance as type I IFN is modulated in SLE and MS. The
      association with autoantibodies and increased IRF8 expression in B cells supports
      a role for rs17445836G in humoral tolerance. 

PMID- 23965943
TI  - Targeted resequencing identifies defective variants of decoy receptor 3 in
      pediatric-onset inflammatory bowel disease.
AB  - Genome-wide association studies have implicated common variation at the 20q13
      locus in inflammatory bowel disease, particularly for the pediatric Crohn's form.
      This locus harbors tumor necrosis factor receptor superfamily (TNFRSF6B),
      encoding a secreted protein, decoy receptor 3 (DcR3), which binds to and
      neutralizes pro-inflammatory cytokines of the tumor necrosis factor superfamily.
      We sought to further the evidence of DcR3's role in pediatric IBD by identifying
      missense mutations with functional significance within TNFRSF6B. We sequenced the
      exons of the gene in 528 Caucasian pediatric IBD cases and 549 Caucasian healthy
      controls to establish the frequency of such events in each population. Sequencing
      revealed that our IBD cohort harbored a greater number of missense variants,
      yielding an odds ratio of 3.9 (P-value=0.005). Using functional assays, we
      established that the frequency of mutants defective in secretion from cultured
      cells was greater in the Crohn's category than in the controls, yielding an odds
      ratio of 7.1 (P-value=0.004). These results suggest that rare defective variants
      in TNFRSF6B have a role in the pathogenesis of some cases of IBD and that
      interventions targeting this group of tumor necrosis factor-family members may
      benefit patients with IBD. 

PMID- 23965944
TI  - Purification, characterization, and properties of an alkaline protease produced
      by Serratia marcescens S3-R1 inhabiting Korean ginseng rhizosphere.
AB  - BACKGROUND: An alkaline protease produced by the Serratia marcescens S3-R1 which
      inhabits in the Korean ginseng rhizosphere was investigated. The purposes of this
      study were to characterize and purify the bacterial enzyme by four different
      purification steps: precipitation of enzyme fraction by ammonium sulfate, loading
      the enzyme pellets on a DEAE-Sepharose anion-exchange chromatograph, separation
      of the fraction containing enzyme activity by fast protein liquid Mono Q
      chromatography and identification of the single-band fraction by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, and then quantification of the single
      band fraction by reverse-phase high-performance liquid chromatography. RESULTS:
      The molecular weight of the purified protease was estimated as 50 308 Da by
      matrix-assisted laser desorption ionization time-of-flight analysis. The N
      terminal amino acid sequence of the protease was identified as Ala-Val-Thr-Ile
      Glu-Asp-Ala-Val-Asp-Asp, and the enzyme belongs to the metalloprotease family.
      The optimal activities of the protease occurred at pH 7-9 and a temperature 40 
      degrees C. The ranges of pH and thermal stability of the enzyme were at 7-10 and
      30-40  degrees C, respectively. CONCLUSION: The alkaline protease was
      successfully purified and characterized from the bacterium Serratia marcescens S3
      R1, which has potential for industrial application, including milk protein
      hydrolysates.

PMID- 23965945
TI  - The temporal profile of postactivation potentiation is related to strength level.
AB  - The purpose of this investigation was to determine whether stronger individuals
      are able to express postactivation potentiation (PAP) earlier than weaker
      individuals during a vertical squat jump test. Eighteen junior elite rugby league
      players were divided into strong (relative 1 repetition maximum [1RM] back squat
      >= 2 * body mass) and weak (relative 1RM back squat <2.0 * body mass) groups.
      Each subject performed squat jumps before, 15 seconds, 3, 6, 9, and 12 minutes
      after a conditioning activity (CA) that contained 1 set of 3 back squats
      performed at 90% of 1RM. A force plate, which sampled at 1000 Hz, was used to
      determine the power output and height for each squat jump. Stronger individuals
      expressed PAP between 3 and 12 minutes post-CA, whereas their weaker counterparts
      displayed potentiation between 6 and 12 minutes post-CA. Moreover, the stronger
      group exhibited a significantly (p <= 0.05) higher PAP response than the weaker
      group at all post-CA squat jump tests. The stronger group displayed the greatest
      potentiation at 6 minutes post-CA, whereas the weaker group displayed the
      greatest potentiation response at 9 minutes following the CA. Based on these
      results, stronger individuals appear to be able to express PAP earlier after a CA
      than weaker individuals. Additionally, stronger individuals express significantly
      greater postactivation responses than weaker individuals. From a practical
      standpoint, strength and conditioning coaches should consider the athletes'
      strength levels when constructing postactivation complexes (CA + performance
      activity) as strength will dictate the time frame required between the
      conditioning and the performance activity.

PMID- 23965946
TI  - Coronary spastic angina is associated with insulin resistance - possible
      involvement of endothelial dysfunction.
AB  - OBJECTIVE: In this study, we examined whether coronary spastic angina (CSA) is
      associated with insulin resistance. BACKGROUND: There is increasing evidence that
      insulin resistance is associated with endothelial dysfunction. Patients with CSA
      show endothelial dysfunction. METHODS: The study participants include 111 CSA
      patients (81 men and 30 women, mean age 62+/-12 years) and 53 participants
      without CSA (24 men and 29 women, mean age 63+/-10 years), serving as the
      controls. The oral glucose tolerance test was performed, and anthropometric
      parameters, plasma glucose and insulin levels, lipid profiles, and other
      laboratory parameters were evaluated. RESULTS: Homeostasis model assessment of
      insulin resistance (HOMA-IR), Log HOMA-IR, the quantitative insulin sensitivity
      check index, the insulin sensitivity index, and insulin resistance 60-120 min
      after glucose load (log post-glucose-IR) were calculated as surrogate markers of
      insulin resistance. The number of men, the number of smokers, log post-glucose
      IR, the insulin sensitivity index, and fasting plasma glucose levels were higher
      in CSA patients compared with controls (P=0.001, 0.001, 0.004, 0.012, and 0.013,
      respectively), whereas plasma high-density lipoprotein cholesterol levels were
      lower (P<0.001). CONCLUSION: Insulin resistance on glucose load (log post-glucose
      IR), plasma high-density lipoprotein cholesterol levels, and smoking were
      significantly associated with CSA (r=0.225, P=0.004; r=-0.313, P<0.001; and
      r=0.258, P=0.001, respectively).

PMID- 23965947
TI  - Validity of the GRACE score for 6-month death or reinfarction after presentation
      with acute myocardial infarction in patients 80 years of age and older.
AB  - INTRODUCTION AND OBJECTIVE: The Global Registry of Acute Coronary Events (GRACE)
      risk score provides a prediction of the probability of death and myocardial
      infarction within 6 months after acute coronary syndrome. Our aim was to detect
      the validity of the GRACE risk score in predicting 6-month death or reinfarction
      in Chinese acute myocardial infarction (AMI) inpatients 80 years of age and older
      between 2003 and 2012. METHODS: Using the GRACE risk score to predict the
      combined endpoints of all-cause death or reinfarction within 6 months of AMI, we
      evaluated its discrimination and calibration by the C-statistic and the Hosmer
      Lemeshow test, respectively. RESULTS: In total, 370 patients presenting with ST
      segment elevation myocardial infarction (STEMI) and non-STEMI were included. The
      GRACE risk score ranged between 181 and 325; death or reinfarction within 6
      months of AMI was 49.2%. The GRACE model showed good discrimination overall (C
      statistic 0.708, 95% confidence interval: 0.655-0.760, P<0.001) and in patients
      with non-STEMI (C-statistic 0.756, 95% confidence interval: 0.690-0.823,
      P<0.001). However, the discriminatory capacity was lower in patients with STEMI
      (C-statistic 0.645, P=0.001). The calibration was optimal overall (Hosmer
      Lemeshow, P=0.398) and in the subgroups (STEMI, P=0.098; non-STEMI, P=0.822).
      There was a high correlation (R=0.926) between the predicted and the observed 6
      month death or reinfarction after AMI. CONCLUSION: The GRACE score is accurate
      for determination of 6-month death or reinfarction in Chinese AMI inpatients 80
      years of age and older; however, the discrimination and calibration performs less
      well in patients with STEMI.

PMID- 23965948
TI  - Preoperative poor coronary collateral circulation can predict the development of
      atrial fibrillation after coronary artery bypass graft surgery.
AB  - AIM: Coronary collateral circulation (CCC) helps to protect and preserve
      myocardium from episodes of ischemia, and reduce angina symptoms, arrhythmia, and
      cardiovascular events. Atrial fibrillation (AF) is the most frequent form of
      arrhythmia after coronary artery bypass graft (CABG) surgery. The aim of this
      study was to investigate the association between CCC and the development of AF in
      patients undergoing CABG surgery. METHODS: A total of 165 patients (mean age 63+/
      10 years, 74% men, 26% women) who were undergoing CABG surgery at our department
      were enrolled into this study. Patients were categorized into two groups
      according to preoperative CCC using the Rentrop method. RESULTS: Of the patients,
      79 had poor CCC and 89 had good CCC. The AF incidence rate in the poor collateral
      group was significantly higher than that in the good collateral group [37 (49%)
      vs. 12 (14%), P<0.001]. In univariate analysis, age, left atrium size, and poor
      CCC grade were associated with AF after CABG surgery. Multivariate analysis
      showed that only poor CCC grade (odds ratio: 11.500; 95% confidence interval
      3.977-33.253, P<0.001) was an independent predictor of the development of AF
      after adjustment of other potential confounders in patients undergoing CABG
      surgery. CONCLUSION: The present study showed that preoperative poor CCC is a
      powerful predictor of the development of AF after CABG surgery.

PMID- 23965949
TI  - Variation in referral practice and differential cancer outcome: a strong reason
      to reflect on whether current guidelines are fit for purpose or implemented
      effectively in primary care.

PMID- 23965951
TI  - From hydrogen bond donor to acceptor: the effect of ethanol fluorination on the
      first solvating water molecule.
AB  - Supersonic jet FTIR spectra of the OH stretching vibrations in complexes of mono
      , di- and trifluoroethanol with water are presented. In contrast to the non
      fluorinated ethanol case, the fluorinated alcohols are all shown to act as O
      H...O hydrogen bond donors towards water. This is found to be mostly a
      consequence of the intramolecular electron-withdrawing effect of the fluorine
      atoms and, with decreasing importance for increasing fluorination, due to the
      attractive intermolecular contact between one of the dangling water OH groups and
      the fluorine atoms. The findings provide a stepwise rationalization for the
      hydrophobic properties of the pharmaceutically important trifluoromethyl group.

PMID- 23965950
TI  - Genetic and environmental influences on the familial transmission of
      externalizing disorders in adoptive and twin offspring.
AB  - IMPORTANCE: Twin-family studies have shown that parent-child resemblance on
      substance use disorders and antisocial behavior can be accounted for by the
      transmission of a general liability to a spectrum of externalizing disorders.
      Most studies, however, include only biological parents and offspring, which
      confound genetic and environmental transmission effects. OBJECTIVE: To examine
      the familial transmission of externalizing disorders among both adoptive
      (genetically unrelated) and biological relatives to better distinguish genetic
      and environmental mechanisms of transmission. DESIGN: Family study design wherein
      each family included the mother, father, and 2 offspring, including monozygotic
      twin, dizygotic twin, nontwin biological, and adoptive offspring. Structural
      equation modeling was used to estimate familial transmission effects and their
      genetic and environmental influences. SETTING: Participants were recruited from
      the community and assessed at a university laboratory. PARTICIPANTS: A total of
      1590 families with biological offspring and 409 families with adoptive offspring.
      Offspring participants were young adults (mean age, 26.2 years). MAIN OUTCOMES
      AND MEASURES: Symptom counts of conduct disorder, adult antisocial behavior, and
      alcohol, nicotine, and drug dependence. RESULTS There was a medium effect for the
      transmission of the general externalizing liability for biological parents (r =
      0.27-0.30) but not for adoptive parents (r = 0.03-0.07). In contrast, adoptive
      siblings exhibited significant similarity on the general externalizing liability
      (r = 0.21). Biometric analyses revealed that the general externalizing liability
      was highly heritable (a2 = 0.61) but also exhibited significant shared
      environmental influences (c2 = 0.20). CONCLUSIONS AND RELEVANCE: Parent-child
      resemblance for substance use disorders and antisocial behavior is primarily due
      to the genetic transmission of a general liability to a spectrum of externalizing
      disorders. Including adoptive siblings revealed a greater role of shared
      environmental influences on the general externalizing liability than previously
      detected in twin studies and indicates that sibling rather than parent-child
      similarity indexes important environmental risk factors for externalizing
      disorders.

PMID- 23965952
TI  - Somatic mutation of KIT is rare in small cell lung cancer patients from Northeast
      China.
AB  - Studies have confirmed that protein overexpression or mutations of KIT are
      involved in growth and development of a variety of cancers. however, little is
      known about data of gene mutation and protein expression in small cell lung
      cancer (SCLC) patients from northeast China.The aim of study is to investigate
      gene mutation and protein expression in such patients with small cell lung cancer
      (SCLC) and analyse their clinical significance.The expression of c-Kit protein
      was analyzed by immunohistochemistry in 77 SCLC samples and 22 normal lung
      samples. KIT mutations were screened in exons 9, 11, 13, 14, 17 and 18 by DNA
      direct sequencing.The study showed that positive staining for c-Kit was observed
      in 28 of 77 SCLC patients . There was no correlations between expression of c-Kit
      and sex, ages, smoking status, stage. only 1 case was found to have known T801I
      mutation in exon 17. The median survival (13.9 months) of cases with c-Kit
      positive was shorter than that (19.9 months) of cases with c-Kit-negative. The
      finding revealed that stages was identified as an independent predictive factor
      for SCLC patients.Our finding reveals that somatic mutation of KIT is rare in
      SCLC patients from the northeast China and there is no enough evidence comfirming
      KIT inhibitors for treatment in SCLC.

PMID- 23965953
TI  - Oxide-based platform for reconfigurable superconducting nanoelectronics.
AB  - We report quasi-1D superconductivity at the interface of LaAlO3 and SrTiO3. The
      material system and nanostructure fabrication method supply a new platform for
      superconducting nanoelectronics. Nanostructures having line widths w ~ 10 nm are
      formed from the parent two-dimensional electron liquid using conductive atomic
      force microscope lithography. Nanowire cross-sections are small compared to the
      superconducting coherence length in LaAlO3/SrTiO3, placing them in the quasi-1D
      regime. Broad superconducting transitions versus temperature and finite
      resistances in the superconducting state well below Tc ~ 200 mK are observed,
      suggesting the presence of fluctuation- and heating-induced resistance. The
      superconducting resistances and V-I characteristics are tunable through the use
      of a back gate. Four-terminal resistances in the superconducting state show an
      unusual dependence on the current path, varying by as much as an order of
      magnitude. This new technology, i.e., the ability to 'write' gate-tunable
      superconducting nanostructures on an insulating LaAlO3/SrTiO3 'canvas', opens
      possibilities for the development of new families of reconfigurable
      superconducting nanoelectronics.

PMID- 23965955
TI  - Domain structures in nematic liquid crystals on a polycarbonate surface.
AB  - Alignment of nematic liquid crystals on polycarbonate films obtained with the use
      of solvents with different solvations is studied. Domain structures occurring
      during the growth on the polymer surface against the background of the initial
      thread-like or schlieren texture are demonstrated. It is established by optical
      methods that the domains are stable formations visualizing the polymer surface
      structures. In nematic droplets, the temperature-induced transition from the
      domain structure with two extinction bands to the structure with four bands is
      observed. This transition is shown to be caused by reorientation of the nematic
      director in the liquid crystal volume from the planar alignment to the
      homeotropic state with the pronounced radial configuration of nematic molecules
      on the surface. The observed textures are compared with different combinations of
      the volume LC orientations and the radial distribution of the director field and
      the disclination lines at the polycarbonate surface. 

PMID- 23965956
TI  - The efficacy of the quorum sensing inhibitor FS8 and tigecycline in preventing
      prosthesis biofilm in an animal model of staphylococcal infection.
AB  - We investigated the efficacy of tigecycline and FS8, alone or combined, in
      preventing prosthesis biofilm in a rat model of staphylococcal vascular graft
      infection. Graft infections were established in the back subcutaneous tissue of
      adult male Wistar rats by implantation of Dacron prostheses followed by topical
      inoculation with 2 x 107 colony-forming units of Staphylococcus aureus, strain
      Smith diffuse. The study included a control group, a contaminated group that did
      not receive any antibiotic prophylaxis, and three contaminated groups that
      received: (i) intraperitoneal tigecycline, (ii) FS8-soaked graft, and (iii)
      tigecycline plus FS8-soaked graft, respectively. Each group included 15 animals.
      The infection burden was evaluated by using sonication and quantitative agar
      culture. Moreover, an in vitro binding-study was performed to quantify the how
      much FS8 was coated to the surface of the prosthesis. Tigecycline, combined with
      FS8, against the adherent bacteria showed MICs (2.00 mg/L) and MBCs (4.00 mg/L)
      four-fold lower with respect to tigecycline alone in in vitro studies. The rat
      groups treated with tigecycline showed the lowest bacterial numbers (4.4 x 104 +/
      1.2 x 104 CFU/mL). The FS8-treated group showed a good activity and significant
      differences compared to control group with bacterial numbers of 6.8 x 104 +/- 2.0
      x 104 CFU/mL. A stronger inhibition of bacterial growth was observed in rats
      treated with a combined FS8 and tigecycline therapy than in those that were
      singly treated with bacterial numbers of 101 CFU/mL graft. In conclusion, the
      ability to affect biofilm formation as well, its property to be an antibiotic
      enhancer suggests FS8 as alternative or additional agent to use in conjunction
      with conventional antimicrobial for prevention of staphylococcal biofilm related
      infection. 

PMID- 23965957
TI  - The effects of biopolymer encapsulation on total lipids and cholesterol in egg
      yolk during in vitro human digestion.
AB  - The purpose of this study was to examine the effect of biopolymer encapsulation
      on the digestion of total lipids and cholesterol in egg yolk using an in vitro
      human digestion model. Egg yolks were encapsulated with 1% cellulose, pectin, or
      chitosan. The samples were then passed through an in vitro human digestion model
      that simulated the composition of mouth saliva, stomach acid, and the intestinal
      juice of the small intestine by using a dialysis tubing system. The change in
      digestion of total lipids was monitored by confocal fluorescence microscopy. The
      digestion rate of total lipids and cholesterol in all egg yolk samples
      dramatically increased after in vitro human digestion. The digestion rate of
      total lipids and cholesterol in egg yolks encapsulated with chitosan or pectin
      was reduced compared to the digestion rate of total lipids and cholesterol in
      other egg yolk samples. Egg yolks encapsulated with pectin or chitosan had lower
      free fatty acid content, and lipid oxidation values than samples without
      biopolymer encapsulation. Moreover, the lipase activity decreased, after in vitro
      digestion, in egg yolks encapsulated with biopolymers. These results improve our
      understanding of the effects of digestion on total lipids and cholesterol in egg
      yolk within the gastrointestinal tract. 

PMID- 23965954
TI  - Principles of miRNA-target regulation in metazoan models.
AB  - MicroRNAs (miRs) are key post-transcriptional regulators that silence gene
      expression by direct base pairing to target sites of RNAs. They have a wide
      variety of tissue expression patterns and are differentially expressed during
      development and disease. Their activity and abundance is subject to various
      levels of control ranging from transcription and biogenesis to miR response
      elements on RNAs, target cellular levels and miR turnover. This review summarizes
      and discusses current knowledge on the regulation of miR activity and concludes
      with novel non-canonical functions that have recently emerged. 

PMID- 23965958
TI  - The role of mitochondrial DNA damage and repair in the resistance of BCR/ABL
      expressing cells to tyrosine kinase inhibitors.
AB  - Chronic myeloid leukemia (CML) is a hematological malignancy that arises from the
      transformation of stem hematopoietic cells by the fusion oncogene BCR/ABL and
      subsequent clonal expansion of BCR/ABL-positive progenitor leukemic cells. The
      BCR/ABL protein displays a constitutively increased tyrosine kinase activity that
      alters many regulatory pathways, leading to uncontrolled growth, impaired
      differentiation and increased resistance to apoptosis featured by leukemic cells.
      Current CML therapy is based on tyrosine kinase inhibitors (TKIs), primarily
      imatinib, which induce apoptosis in leukemic cells. However, some patients show
      primary resistance to TKIs while others develop it in the course of therapy. In
      both cases, resistance may be underlined by perturbations in apoptotic signaling
      in leukemic cells. As mitochondria may play an important role in such signaling,
      alteration in mitochondrial metabolism may change resistance to pro-apoptotic
      action of TKIs in BCR/ABL-positive cells. Because BCR/ABL may induce reactive
      oxygen species and unfaithful DNA repair, it may affect the stability of
      mitochondrial DNA, influencing mitochondrial apoptotic signaling and in this way
      change the sensitivity of CML cells to TKIs. Moreover, cancer cells, including
      BCR/ABL-positive cells, show an increased level of glucose metabolism, resulting
      from the shift from oxidative phosphorylation to glycolysis to supply ATP for
      extensive proliferation. Enhanced level of glycolysis may be associated with TKI
      resistance and requires change in the expression of several genes regulated
      mostly by hypoxia-inducible factor-1alpha, HIF-1alpha. Such regulation may be
      associated with the impaired mitochondrial respiratory system in CML cells. In
      summary, mitochondria and mitochondria-associated molecules and pathways may be
      attractive targets to overcome TKI resistance in CML.

PMID- 23965960
TI  - Quorum sensing in the squid-Vibrio symbiosis.
AB  - Quorum sensing is an intercellular form of communication that bacteria use to
      coordinate group behaviors such as biofilm formation and the production of
      antibiotics and virulence factors. The term quorum sensing was originally coined
      to describe the mechanism underlying the onset of luminescence production in
      cultures of the marine bacterium Vibrio fischeri. Luminescence and, more
      generally, quorum sensing are important for V. fischeri to form a mutualistic
      symbiosis with the Hawaiian bobtail squid, Euprymna scolopes. The symbiosis is
      established when V. fischeri cells migrate via flagella-based motility from the
      surrounding seawater into a specialized structure injuvenile squid called the
      light organ. The cells grow to high cell densities within the light organ where
      the infection persists over the lifetime of the animal. A hallmark of a
      successful symbiosis is the luminescence produced by V. fischeri that camouflages
      the squid at night by eliminating its shadow within the water column. While the
      regulatory networks governing quorum sensing are critical for properly regulating
      V. fischeri luminescence within the squid light organ, they also regulate
      luminescence-independent processes during symbiosis. In this review, we discuss
      the quorum-sensing network of V. fischeri and highlight its impact at various
      stages during host colonization. 

PMID- 23965959
TI  - Molecular pathways involved in colorectal cancer: implications for disease
      behavior and prevention.
AB  - Research conducted during the past 30 years has increased our understanding of
      the mechanisms involved in colorectal cancer initiation and development. The
      findings have demonstrated the existence of at least three pathways: chromosomal
      instability, microsatellite instability and CpG island methylator phenotype.
      Importantly, new studies have shown that inflammation and microRNAs contribute to
      colorectal carcinogenesis. Recent data have demonstrated that several genetic and
      epigenetic changes are important in determining patient prognosis and survival.
      Furthermore, some of these mechanisms are related to patients' response to drugs,
      such as aspirin, which could be used for both chemoprevention and treatment in
      specific settings. Thus, in the near future, we could be able to predict disease
      behavior based on molecular markers found on tumors, and direct the best
      treatment options for patients.

PMID- 23965961
TI  - Influence of genetic variations on levels of inflammatory markers of healthy
      subjects at baseline and one week after clopidogrel therapy; results of a
      preliminary study.
AB  - We aimed to assess the association between the most common polymorphisms of
      cytochrome P450 (CYP) epoxygenases on the plasma levels of inflammatory markers
      in a population of healthy subjects. We also sought to determine whether CYP2C19
      2 polymorphism is associated with the anti-inflammatory response to clopidogrel.
      In a population of 49 healthy young males, the baseline plasma levels of
      inflammatory markers including C-reactive protein, haptoglobin, orosomucoid acid,
      CD-40 were compared in carriers vs. non-carriers of the most frequent CYP
      epoxygenase polymorphisms: CYP2C9 2, CYP2C9 3, CYP2C19 2, CYP2C8 2 and CYP2J2 7.
      Also, the variation of inflammatory markers from baseline to 7 days after
      administration of 75 mg per day of clopidogrel were compared in carriers vs. non
      carriers of CYP2C19 allele and also in responders vs. hypo-responders to
      clopidogrel, determined by platelet reactivity tests. There was no significant
      association between epoxygenase polymorphisms and the baseline levels of
      inflammatory markers. Likewise, CYP2C19 allele was not associated with anti
      inflammatory response to clopidogrel. Our findings did not support the notion
      that the genetic variations of CYP epoxygenases are associated with the level of
      inflammatory markers. Moreover, our results did not support the hypothesis that
      CYP2C19 2 polymorphism is associated with the variability in response to the anti
      inflammatory properties of clopidogrel.

PMID- 23965962
TI  - Liquid crystal phase behaviour of attractive disc-like particles.
AB  - We employ a generalized van der Waals-Onsager perturbation theory to construct a
      free energy functional capable of describing the thermodynamic properties and
      orientational order of the isotropic and nematic phases of attractive disc
      particles. The model mesogen is a hard (purely repulsive) cylindrical disc
      particle decorated with an anisotropic square-well attractive potential placed at
      the centre of mass. Even for isotropic attractive interactions, the resulting
      overall inter-particle potential is anisotropic, due to the orientation-dependent
      excluded volume of the underlying hard core. An algebraic equation of state for
      attractive disc particles is developed by adopting the Onsager trial function to
      characterize the orientational order in the nematic phase. The theory is then
      used to represent the fluid-phase behaviour (vapour-liquid, isotropic-nematic,
      and nematic-nematic) of the oblate attractive particles for varying values of the
      molecular aspect ratio and parameters of the attractive potential. When compared
      to the phase diagram of their athermal analogues, it is seen that the addition of
      an attractive interaction facilitates the formation of orientationally-ordered
      phases. Most interestingly, for certain aspect ratios, a coexistence between two
      anisotropic nematic phases is exhibited by the attractive disc-like fluids.

PMID- 23965964
TI  - A nitric oxide-responsive quorum sensing circuit in Vibrio harveyi regulates
      flagella production and biofilm formation.
AB  - Cell signaling plays an important role in the survival of bacterial colonies.
      They use small molecules to coordinate gene expression in a cell density
      dependent manner. This process, known as quorum sensing, helps bacteria regulate
      diverse functions such as bioluminescence, biofilm formation and virulence. In
      Vibrio harveyi, a bioluminescent marine bacterium, four parallel quorum-sensing
      systems have been identified to regulate light production. We have previously
      reported that nitric oxide (NO), through the H-NOX/HqsK quorum sensing pathway
      contributes to light production in V. harveyi through the LuxU/LuxO/LuxR quorum
      sensing pathway. In this study, we show that nitric oxide (NO) also regulates
      flagellar production and enhances biofilm formation. Our data suggest that V.
      harveyi is capable of switching between lifestyles to be able to adapt to changes
      in the environment. 

PMID- 23965965
TI  - Correlation of dual colour single particle trajectories for improved detection
      and analysis of interactions in living cells.
AB  - Interactions between objects inside living cells are often investigated by
      looking for colocalization between fluorescence microscopy images that are
      recorded in separate colours corresponding to the fluorescent label of each
      object. The fundamental limitation of this approach in the case of dynamic
      objects is that coincidental colocalization cannot be distinguished from true
      interaction. Instead, correlation between motion trajectories obtained by dual
      colour single particle tracking provides a much stronger indication of
      interaction. However, frequently occurring phenomena in living cells, such as
      immobile phases or transient interactions, can limit the correlation to small
      parts of the trajectories. The method presented here, developed for the detection
      of interaction, is based on the correlation inside a window that is scanned along
      the trajectories, covering different subsets of the positions. This scanning
      window method was validated by simulations and, as an experimental proof of
      concept, it was applied to the investigation of the intracellular trafficking of
      polymeric gene complexes by endosomes in living retinal pigment epithelium cells,
      which is of interest to ocular gene therapy. 

PMID- 23965963
TI  - Exploring the role of genetic variability and lifestyle in oxidative stress
      response for healthy aging and longevity.
AB  - Oxidative stress is both the cause and consequence of impaired functional
      homeostasis characterizing human aging. The worsening efficiency of stress
      response with age represents a health risk and leads to the onset and accrual of
      major age-related diseases. In contrast, centenarians seem to have evolved
      conservative stress response mechanisms, probably derived from a combination of a
      diet rich in natural antioxidants, an active lifestyle and a favorable genetic
      background, particularly rich in genetic variants able to counteract the stress
      overload at the level of both nuclear and mitochondrial DNA. The integration of
      these factors could allow centenarians to maintain moderate levels of free
      radicals that exert beneficial signaling and modulator effects on cellular
      metabolism. Considering the hot debate on the efficacy of antioxidant
      supplementation in promoting healthy aging, in this review we gathered the
      existing information regarding genetic variability and lifestyle factors which
      potentially modulate the stress response at old age. Evidence reported here
      suggests that the integration of lifestyle factors (moderate physical activity
      and healthy nutrition) and genetic background could shift the balance in favor of
      the antioxidant cellular machinery by activating appropriate defense mechanisms
      in response to exceeding external and internal stress levels, and thus possibly
      achieving the prospect of living a longer life. 

PMID- 23965966
TI  - MicroRNA-143 downregulates interleukin-13 receptor alpha1 in human mast cells.
AB  - MicroRNA-143 (miR-143) was found to be downregulated in allergic rhinitis, and
      bioinformatics analysis predicted that IL-13Ralpha1 was a target gene of miR-143.
      To understand the molecular mechanisms of miR-143 involved in the pathogenesis of
      allergic inflammation, recombinant miR-143 plasmid vectors were constructed, and
      human mast cell-1(HMC-1) cells which play a central role in the allergic response
      were used for study. The plasmids were transfected into HMC-1 cells using a
      lentiviral vector. Expression of IL-13Ralpha1 mRNA was then detected by reverse
      transcriptase polymerase chain reaction (RT-PCR) and Western Blotting. The miR
      143 lentiviral vector was successfully stably transfected in HMC-1 cells for
      target gene expression. Compared to the control, the target gene IL-13Ralpha1 was
      less expressed in HMC-1 transfected with miR-143 as determined by RT-PCR and
      Western Blotting (p < 0.05); this difference in expression was statistically
      significant and the inhibition efficiency was 71%. It indicates that miR-143
      directly targets IL-13Ralpha1 and suppresses IL-13Ralpha1 expression in HMC-1
      cells. Therefore, miR-143 may be associated with allergic reaction in human mast
      cells.

PMID- 23965967
TI  - Structural properties of polyphenols causing cell cycle arrest at G1 phase in
      HCT116 human colorectal cancer cell lines.
AB  - Plant-derived polyphenols are being tested as chemopreventive agents; some
      polyphenols arrest the cell cycle at G1 phase, whereas others inhibit cell cycle
      proliferation at G2/M phase. Therefore, polyphenols have been proposed to inhibit
      cell cycle progression at different phases via distinct mechanisms. Indeed, our
      previous studies showed that small structural differences in polyphenols cause
      large differences in their biological activities; however, the details of the
      structural properties causing G1 cell cycle arrest remain unknown. In this study,
      we prepared 27 polyphenols, including eight different scaffolds, to gain insight
      into the structural conditions that arrest the cell cycle at G1 phase in a
      quantitative structure-activity relationship study. We used cell cycle profiles
      to determine the biophores responsible for G1 cell cycle arrest and believe that
      the biophores identified in this study will help design polyphenols that cause G1
      cell cycle arrest. 

PMID- 23965968
TI  - Decreased expression of alpha-L-fucosidase gene FUCA1 in human colorectal tumors.
AB  - In previous studies we described a decreased alpha-L-fucosidase activity in
      colorectal tumors, appearing as a prognostic factor of tumoral recurrence. The
      aim of this work was to extend the knowledge about tissue alpha-L-fucosidase in
      colorectal cancer by quantifying the expression of its encoding gene FUCA1 in
      tumors and healthy mucosa. FUCA1 mRNA levels were measured by RT-qPCR in paired
      tumor and normal mucosa tissues from 31 patients. For the accuracy of the RT-qPCR
      results, five candidate reference genes were validated in those samples. In
      addition, activity and expression of alpha-L-fucosidase in selected matched tumor
      and healthy mucosa samples were analyzed. According to geNorm and NormFinder
      algorithms, RPLP0 and HPRT1 were the best reference genes in colorectal tissues.
      These genes were used for normalization of FUCA1 expression levels. A significant
      decrease of more than 60% in normalized FUCA1 expression was detected in tumors
      compared to normal mucosa (p = 0.002). Moreover, a gradual decrease in FUCA1
      expression was observed with progression of disease from earlier to advanced
      stages. These findings were confirmed by Western blot analysis of alpha-L
      fucosidase expression. Our results demonstrated diminished FUCA1 mRNA levels in
      tumors, suggesting that expression of tissue alpha-L-fucosidase could be
      regulated at transcriptional level in colorectal cancer.

PMID- 23965969
TI  - Regulation of huntingtin gene expression by miRNA-137, -214, -148a, and their
      respective isomiRs.
AB  - With the advent of deep sequencing technology, a variety of miRNA length and
      sequence variants, termed isomiRNAs (isomiRs), have been discovered. However, the
      functional roles of these commonly detected isomiRs remain unknown. In this
      paper, we demonstrated that miRNAs regulate the expression of the HTT gene, whose
      mutation leads to Huntington's disease (HD), a hereditary degenerative disorder.
      Specifically, we validated the interactions of canonical miRNAs, miR-137, miR
      214, and miR-148a, with the HTT 3'UTR using a luciferase assay. Moreover, we
      applied synthetic miRNA mimics to examine whether a slight shifting of miRNA seed
      regions might alter the regulation of the HTT transcript. We also examined miR
      137, miR-214, and miR-148a isomiRs and showed the activity of these isoforms on
      reporter constructs bearing appropriate sequences from the HTT 3'UTR. Hence, we
      demonstrated that certain 5'-end variants of miRNAs might be functional for the
      regulation of the same targets as canonical miRNAs.

PMID- 23965970
TI  - Inhibition of NADPH oxidase by apocynin attenuates progression of
      atherosclerosis.
AB  - Of the multiple sources of reactive oxygen species (ROS) in the blood vessel,
      NADPH oxidases are the primary source. Whereas several studies have implicated
      NADPH oxidases in the initiation of atherosclerosis, their roles in disease
      progression are incompletely understood. Our objective was to determine the
      potential clinical relevance of inhibiting NADPH oxidase in established
      atherosclerosis. Using a hypercholesteremic murine model of atherosclerosis (ApoE
      /-/LDLR-/- (AS) mice on normal chow diet), we first established a time-dependent
      relationship between superoxide levels and lesion size in AS mice. Next, we
      identified NADPH oxidase as the primary source of ROS in atherosclerotic lesions.
      Treatment of aortic segments from AS mice with apocynin, which interferes with
      NADPH oxidase activation in part by preventing translocation of the subunit
      p47phox, significantly reduced superoxide levels. Moreover, addition of apocynin
      to the drinking water of AS mice produced a decrease in lesion size as compared
      to untreated AS mice, with the effect most pronounced in the thoracoabdominal
      aorta but absent from the aortic arch. Granulocyte function in AS+apocynin mice
      was suppressed, confirming efficacy of apocynin treatment. We conclude that
      apocynin attenuates the progression of atherosclerosis in hypercholesterolemic
      mice, potentially by its ability to inhibit generation of superoxide by NADPH
      oxidase.

PMID- 23965971
TI  - UVB-stimulated TNFalpha release from human melanocyte and melanoma cells is
      mediated by p38 MAPK.
AB  - Ultraviolet (UV) radiation activates cell signaling pathways in melanocytes. As a
      result of altered signaling pathways and UV-induced cellular damage, melanocytes
      can undergo oncogenesis and develop into melanomas. In this study, we
      investigated the effect of UV-radiation on p38 MAPK (mitogen-activated protein
      kinase), JNK and NFkappaB pathways to determine which plays a major role in
      stimulating TNFalpha secretion in human HEM (melanocytes) and MM96L (melanoma)
      cells. MM96L cells exhibited 3.5-fold higher p38 activity than HEM cells at 5 min
      following UVA + B radiation and 1.6-fold higher JNK activity at 15-30 min
      following UVB+A radiation, while NFkappaB was minimally activated in both cells.
      Irradiated HEM cells had the greatest fold of TNFalpha secretion (UVB: 109-fold,
      UVA + B: 103-fold & UVB+A: 130-fold) when co-exposed to IL1alpha. The p38
      inhibitor, SB202190, inhibited TNFalpha release by 93% from UVB-irradiated HEM
      cells. In the UVB-irradiated MM96L cells, both SB202190 and sulfasalazine
      (NFkappaB inhibitor) inhibited TNFalpha release by 52%. Although, anisomycin was
      a p38 MAPK activator, it inhibited TNFalpha release in UV-irradiated cells. This
      suggests that UV-mediated TNFalpha release may occur via different p38 pathway
      intermediates compared to those stimulated by anisomycin. As such, further
      studies into the functional role p38 MAPK plays in regulating TNFalpha release in
      UV-irradiated melanocyte-derived cells are warranted.

PMID- 23965972
TI  - Molecular cloning, characterization and mRNA expression of a chitin synthase 2
      gene from the oriental fruit fly, Bactrocera dorsalis (Diptera: Tephritidae).
AB  - Chitin synthase (CHS), a potential target for eco-friendly insecticides, plays an
      essential role in chitin formation in insects. In this study, a full-length cDNA
      encoding chitin synthase 2 (BdCHS2) was cloned and characterized in the oriental
      fruit fly, Bactrocera dorsalis. The BdCHS2 cDNA had 4417 nucleotides, containing
      an open reading frame of 4122 nucleotides, which encoded 1373 amino acid residues
      with a predicted molecular weight of 158.5 kDa. Phylogenetic analysis with other
      insect CHSs suggested that BdCHS2 belongs to insect CHS2. The BdCHS2 transcript
      was predominately found in midgut but was detected at low levels in fat body,
      Malpighian tubules, integument, and trachea. Moreover, BdCHS2 was expressed in
      all developmental stages, and highly expressed in the feeding stages. There was a
      positive relationship between BdCHS2 expression and total chitin content during
      development. Furthermore, both the gene expression and chitin content in midgut
      decreased when the insect was fed for 24 h, then starved for 24 h, while they
      increased dramatically and rapidly under the condition of starvation for 24 h
      then feeding for 24 h. These results suggest that BdCHS2 may play an important
      role in regulating chitin content of the midgut, and subsequently affect the
      growth and development of B. dorsalis.

PMID- 23965973
TI  - Effects of reduced prolamin on seed storage protein composition and the
      nutritional quality of rice.
AB  - Rice seed storage proteins accumulate in two types of protein body (PB-I and PB
      II) that are nutrient sources for animals. PB-I is indigestible and negatively
      affects rice protein quality. To improve the nutritional value of rice seeds we
      are aiming to engineer the composition and accumulation of endogenous seed
      storage proteins. In this study we generated transgenic rice plants in which 13
      kD prolamin genes were suppressed by RNA interference (13 kD pro-RNAi). Analysis
      based on qRT-PCR confirmed that the targeted 13 kD prolamins were markedly
      suppressed, and were compensated for by an increase in other storage proteins
      including 10 kD prolamin, glutelins, and chaperone proteins. The storage protein
      profiles further revealed that the levels of 13 kD prolamins were significantly
      reduced, while that of the glutelin precursor was slightly increased and the
      remaining storage proteins did not change. Amino acid analysis showed that the
      reduction of 13 kD prolamins resulted in a 28% increase in the lysine content
      relative to the wild type, indicating that the 13 kD pro-RNAi rice seeds are more
      nutritious. Furthermore, a reduction in the levels of 13 kD prolamins resulted in
      abnormal formation of PB-I, which was small and had no lamellar structure. These
      results suggest that alteration of prolamins can contribute to improving the
      nutritional quality of rice. 

PMID- 23965975
TI  - NF90 in posttranscriptional gene regulation and microRNA biogenesis.
AB  - Gene expression patterns are effectively regulated by turnover and translation
      regulatory (TTR) RNA-binding proteins (RBPs). The TTR-RBPs control gene
      expression at posttranscriptional levels, such as pre-mRNA splicing, mRNA
      cytoplasmic export, turnover, storage, and translation. Double-stranded RNA
      binding proteins (DSRBPs) are known to regulate many processes of cellular
      metabolism, including transcriptional control, translational control, mRNA
      processing and localization. Nuclear factor 90 (NF90), one of the DSRBPs, is
      abundantly expressed in vertebrate tissue and participates in many aspects of RNA
      metabolism. NF90 was originally purified as a component of a DNA binding complex
      which binds to the antigen recognition response element 2 in the interleukin 2
      promoter. Recent studies have provided us with interesting insights into its
      possible physiological roles in RNA metabolism, including transcription,
      degradation, and translation. In addition, it was shown that NF90 regulates
      microRNA expression. In this review, we try to focus on the function of NF90 in
      posttranscriptional gene regulation and microRNA biogenesis.

PMID- 23965976
TI  - Homoserine lactones influence the reaction of plants to rhizobia.
AB  - Bacterial quorum sensing molecules not only grant the communication within
      bacterial communities, but also influence eukaryotic hosts. N-acyl-homoserine
      lactones (AHLs) produced by pathogenic or beneficial bacteria were shown to
      induce diverse reactions in animals and plants. In plants, the reaction to AHLs
      depends on the length of the lipid side chain. Here we investigated the impact of
      two bacteria on Arabidopsis thaliana, which usually enter a close symbiosis with
      plants from the Fabaceae (legumes) family and produce a long-chain AHL
      (Sinorhizobium meliloti) or a short-chain AHL (Rhizobium etli). We demonstrate
      that, similarly to the reaction to pure AHL molecules, the impact, which the
      inoculation with rhizosphere bacteria has on plants, depends on the type of the
      produced AHL. The inoculation with oxo-C14-HSL-producing S. meliloti strains
      enhanced plant resistance towards pathogenic bacteria, whereas the inoculation
      with an AttM lactonase-expressing S. meliloti strain did not. Inoculation with
      the oxo-C8-HSL-producing R. etli had no impact on the resistance, which is in
      agreement with our previous hypothesis. In addition, plants seem to influence the
      availability of AHLs in the rhizosphere. Taken together, this report provides new
      insights in the role of N-acyl-homoserine lactones in the inter-kingdom
      communication at the root surface.

PMID- 23965974
TI  - Non-coding RNAs and cancer.
AB  - The discovery of the biological relevance of non-coding RNA (ncRNAs) molecules
      represents one of the most significant advances in contemporary molecular
      biology. Expression profiling of human tumors, based on the expression of miRNAs
      and other short or long ncRNAs, has identified signatures associated with
      diagnosis, staging, progression, prognosis, and response to treatment. In this
      review we will discuss the recent remarkable advancement in the understanding the
      biological functions of human ncRNAs in cancer, the mechanisms of expression and
      the therapeutic potential. 

PMID- 23965977
TI  - Cucurbitacin E as inducer of cell death and apoptosis in human oral squamous cell
      carcinoma cell line SAS.
AB  - Human oral squamous cell carcinoma (OSCC) is a common form of malignant cancer,
      for which radiotherapy or chemotherapy are the main treatment methods.
      Cucurbitacin E (CuE) is a natural compound previously shown to be an antifeedant
      as well as a potent chemopreventive agent against several types of cancer. The
      present study investigates anti-proliferation (using MTT assay, CuE demonstrated
      cytotoxic activity against SAS cell with IC50 values at 3.69 uM) and induced
      apoptosis of human oral squamous cell carcinoma SAS cells after 24 h treatment
      with CuE. Mitochondrial membrane potential (MMP) and caspase activity were
      studied and our results indicate that CuE inhibits cell proliferation as well as
      the activation of apoptois in SAS cells. Both effects increased in proportion to
      the dosage of CuE and apoptosis was induced via mitochondria- and caspase
      dependent pathways. CuE can induce cell death by a mechanism that is not
      dependent on apoptosis induction, and thus represents a promising anticancer
      agent for prevention and treatment of OSCC.

PMID- 23965978
TI  - Molecular interactions in the development of brain metastases.
AB  - Brain metastases are a much-feared complication of cancer. The development of
      brain metastases requires a malignant cell to acquire characteristics that
      facilitate dissemination away from the primary site, entrance into the nervous
      system, and establishment in the brain. This review summarizes recent work
      focused on the molecular derangements leading to brain metastases and outlines
      areas in need of greater understanding. 

PMID- 23965980
TI  - Design, synthesis and antiviral activity studies of schizonepetin derivatives.
AB  - A series of schizonepetin derivatives have been designed and synthesized in order
      to obtain potent antivirus agents. The antiviral activity against HSV-1 and
      influenza virus H3N2 as well as the cytotoxicity of these derivatives was
      evaluated by using cytopathic effect (CPE) inhibition assay in vitro. Compounds
      M2, M4, M5 and M34 showed higher inhibitory activity against HSV-1 virus with the
      TC50 values being in micromole. Compounds M28, M33, and M35 showed higher
      inhibitory activity against influenza virus H3N2 with their TC50 values being
      96.4, 71.0 and 75.4 MUM, respectively. Preliminary biological activity evaluation
      indicated that the anti-H3N2 and anti-HSV-1 activities improved obviously through
      the introduction of halogen into the structure of schizonepetin. 

PMID- 23965979
TI  - Preventive or potential therapeutic value of nutraceuticals against ionizing
      radiation-induced oxidative stress in exposed subjects and frequent fliers.
AB  - Humans are constantly exposed to ionizing radiation deriving from outer space
      sources or activities related to medical care. Absorption of ionizing radiation
      doses over a prolonged period of time can result in oxidative damage and cellular
      dysfunction inducing several diseases, especially in ageing subjects. In this
      report, we analyze the effects of ionizing radiation, particularly at low doses,
      in relation to a variety of human pathologies, including cancer, and
      cardiovascular and retinal diseases. We discuss scientific data in support of
      protection strategies by safe antioxidant formulations that can provide
      preventive or potential therapeutic value in response to long-term diseases that
      may develop following exposure. 

PMID- 23965981
TI  - Post-transcriptional controls by ribonucleoprotein complexes in the acquisition
      of drug resistance.
AB  - Acquisition of drug resistance leads to failure of anti-cancer treatments and
      therapies. Although several successive chemotherapies are available, along with
      efforts towards clinical applications of new anti-cancer drugs, it is generally
      realized that there is a long way to go to treat cancers. Resistance to anti
      cancer drugs results from various factors, including genetic as well as
      epigenetic differences in tumors. Determining the molecular and cellular
      mechanisms responsible for the acquisition of drug resistance may be a helpful
      approach for the development of new therapeutic strategies to overcome treatment
      failure. Several studies have shown that the acquisition of drug resistance is
      tightly regulated by post-transcriptional regulators such as RNA binding proteins
      (RBPs) and microRNAs (miRNAs), which change the stability and translation of
      mRNAs encoding factors involved in cell survival, proliferation, epithelial
      mesenchymal transition, and drug metabolism. Here, we review our current
      understanding of ribonucleoprotein complexes, including RBPs and miRNAs, which
      play critical roles in the acquisition of drug resistance and have potential
      clinical implications for cancer.

PMID- 23965983
TI  - p53 increases MHC class I expression by upregulating the endoplasmic reticulum
      aminopeptidase ERAP1.
AB  - The p53 tumour suppressor has an important role in cancer cells. Here we show
      that p53 regulates expression of major histocompatibility complex I on the cell
      surface. We show that the tumour cell line HCT116, which lacks p53 exhibits
      significantly lower major histocompatibility complex I expression than its wild
      type counterpart. Using a combination of chromatin immunoprecipitation sequencing
      and gene expression analysis, we demonstrate that p53 upregulates expression of
      endoplasmic reticulum aminopeptidase 1 by binding to its cognate response element
      in the ERAP1 gene. Silencing of p53 decreases endoplasmic reticulum
      aminopeptidase 1 protein levels and therefore major histocompatibility complex I
      expression. We further show that this mechanism operates in A549 cells infected
      with H1N1 influenza virus, in which H1N1 activates p53, leading to endoplasmic
      reticulum aminopeptidase 1 upregulation and a corresponding increase in major
      histocompatibility complex I expression. Our study suggests a previously
      unrecognized link between p53 function and the immunosurveillance of cancer and
      infection. 

PMID- 23965982
TI  - Environmental stimuli shape biofilm formation and the virulence of periodontal
      pathogens.
AB  - Periodontitis is a common inflammatory disease affecting the tooth-supporting
      structures. It is initiated by bacteria growing as a biofilm at the gingival
      margin, and communication of the biofilms differs in health and disease. The
      bacterial composition of periodontitis-associated biofilms has been well
      documented and is under continual investigation. However, the roles of several
      host response and inflammation driven environmental stimuli on biofilm formation
      is not well understood. This review article addresses the effects of
      environmental factors such as pH, temperature, cytokines, hormones, and oxidative
      stress on periodontal biofilm formation and bacterial virulence. 

PMID- 23965985
TI  - Lived experiences in help-seeking from the perspective of a mother with a dual
      diagnosis.
AB  - Mothers with a co-occurring mental illness and substance abuse (dual diagnosis)
      use numerous different services. Help-seeking and engagement are complex
      processes which have not yet been sufficiently conceptualized. A descriptive
      phenomenological approach was used to explore these experiences from different
      service contexts and to describe the decisions in and structure of help-seeking
      over a 13-year period. Four in-depth interviews were conducted and data were
      analysed with a descriptive phenomenological method developed by Giorgi. The
      essential meaning structure is an inner conflict within the client, including a
      realization that change starts from within. The essential meaning structure
      combines the other meaning structures: disbelief of receiving help and admitting
      the need for help, keeping up the perfect facade and the risk of total collapse,
      being given and making own choices regarding care and being forced to use
      services and inner emptiness and search for contentment in life. It is possible
      that clients in the help-seeking process do not always recognize they have a need
      for care. If the client experiences inner powerlessness as emptiness and
      resistance to being helped, it is probably not possible to create relationships
      with care providers. Clients may have several ambiguous inner processes which
      prevent them from accepting the need for care. Theoretically and empirically a
      long-term approach is crucial, since the inner transformative processes take
      time. The services can contribute new experiences to the personal level of
      understanding and decision-making, if they consider the experiential level of
      their clients. 

PMID- 23965986
TI  - The letrozole phase 1 metabolite carbinol as a novel probe drug for UGT2B7.
AB  - Carbinol [4,4'-(hydroxymethylene)dibenzonitrile] is the main phase 1 metabolite
      of letrozole, a nonsteroidal aromatase inhibitor used for endocrine therapy in
      postmenopausal breast cancer. We elucidated the contribution of UDP
      glucuronosyltransferase (UGT) isoforms on the glucuronidation of carbinol.
      Identification of UGT isoforms was performed using a panel of recombinant human
      UGT enzymes. Kinetic studies were done in recombinant human UGT2B7 and pooled
      human liver microsomes (HLMs). A liquid chromatography-tandem mass spectrometry
      method was used for detection of metabolites. To assess the impact of UGT2B7*2,
      we determined the carbinol glucuronidation activity using HLM as well as UGT2B7
      protein expression in 148 human livers. Moreover, we analyzed the plasma
      concentrations of 60 letrozole-treated breast cancer patients. We identified
      UGT2B7 as the predominant UGT isoform involved in carbinol glucuronidation. In
      HLMs and recombinant UGT2B7, we determined K(m) values (9.99 and 9.56 uM) and
      V(max) values (3430 and 2399 pmol/min per milligram of protein), respectively. In
      the set of 148 human livers, carbinol glucuronidation activity significantly
      correlated with UGT2B7 protein as determined by Western blotting (r(s) = 0.5088,
      P < 0.0001). Neither carbinol glucuronidation activity (*1/*1: n = 25, 2434 +/-
      1018; *1/*2: n = 80, 2356 +/- 1372; *2/*2: n = 43, 2251 +/- 1421 pmol/min per
      milligram of protein) nor UGT2B7 protein expression was altered by the UGT2B7*2
      genotype. No impact of UGT2B7*2 on plasma levels of carbinol and carbinol-gluc
      [bis(4-cyanophenyl)methyl hexopyranosiduronic acid] in 60 letrozole-treated
      patients was found. Taken together, these findings suggest carbinol as a novel in
      vitro probe substrate for UGT2B7. In vitro and in vivo data suggest a lack of
      influence of the UGT2B7*2 polymorphism on carbinol glucuronidation.

PMID- 23965988
TI  - Long-term water temperature reconstructions from mountain lakes with different
      catchment and morphometric features.
AB  - Long-term water temperature records are necessary for better understanding
      climate change impacts on freshwaters. We reconstruct summer water temperatures
      from three climatically sensitive mountain lakes in Austria using
      paleolimnological methods aiming to examine long-term thermal dynamics and lakes'
      responses to regional climate variability since the Little Ice Age. Our results
      indicate divergent trends for the lakes. In two of the lakes, which are located
      at the sunny southern slope of mountains, water temperature has increased several
      degrees concurrent with the observed air temperature increase. In contrast, no
      change is observed in the reconstructed water temperatures of a shaded lake,
      located at the northern slope, where also the ecological and thermal changes are
      most subtle. The results indicate the importance of cold water inputs, such as
      snowmelt and groundwater, on lakes' thermal conditions and suggest that watershed
      characteristics and lake stratification play a major role in defining the lake
      specific thermal regime. 

PMID- 23965987
TI  - Autophagy sustains mitochondrial glutamine metabolism and growth of BrafV600E
      driven lung tumors.
AB  - Autophagic elimination of defective mitochondria suppresses oxidative stress and
      preserves mitochondrial function. Here, the essential autophagy gene Atg7 was
      deleted in a mouse model of BrafV600E-induced lung cancer in the presence or
      absence of the tumor suppressor Trp53. Atg7 deletion initially induced oxidative
      stress and accelerated tumor cell proliferation in a manner indistinguishable
      from Nrf2 ablation. Compound deletion of Atg7 and Nrf2 had no additive effect,
      suggesting that both genes modulate tumorigenesis by regulating oxidative stress
      and revealing a potential mechanism of autophagy-mediated tumor suppression. At
      later stages of tumorigenesis, Atg7 deficiency resulted in an accumulation of
      defective mitochondria, proliferative defects, reduced tumor burden, conversion
      of adenomas and adenocarcinomas to oncocytomas, and increased mouse life span.
      Autophagy-defective tumor-derived cell lines were impaired in their ability to
      respire and survive starvation and were glutamine-dependent, suggesting that
      autophagy-supplied substrates from protein degradation sustains BrafV600E tumor
      growth and metabolism. SIGNIFICANCE: The essential autophagy gene Atg7 functions
      to promote BrafV600E-driven lung tumorigenesis by preserving mitochondrial
      glutamine metabolism. This suggests that inhibiting autophagy is a novel approach
      to treating BrafV600E-driven cancers.

PMID- 23965989
TI  - A pivotal role for tryptophan 447 in enzymatic coupling of human endothelial
      nitric oxide synthase (eNOS): effects on tetrahydrobiopterin-dependent catalysis
      and eNOS dimerization.
AB  - Tetrahydrobiopterin (BH4) is a required cofactor for the synthesis of NO by NOS.
      Bioavailability of BH4 is a critical factor in regulating the balance between NO
      and superoxide production by endothelial NOS (eNOS coupling). Crystal structures
      of the mouse inducible NOS oxygenase domain reveal a homologous BH4-binding site
      located in the dimer interface and a conserved tryptophan residue that engages in
      hydrogen bonding or aromatic stacking interactions with the BH4 ring. The role of
      this residue in eNOS coupling remains unexplored. We overexpressed human eNOS
      W447A and W447F mutants in novel cell lines with tetracycline-regulated
      expression of human GTP cyclohydrolase I, the rate-limiting enzyme in BH4
      synthesis, to determine the importance of BH4 and Trp-447 in eNOS uncoupling. NO
      production was abolished in eNOS-W447A cells and diminished in cells expressing
      W447F, despite high BH4 levels. eNOS-derived superoxide production was
      significantly elevated in W447A and W447F versus wild-type eNOS, and this was
      sufficient to oxidize BH4 to 7,8-dihydrobiopterin. In uncoupled, BH4-deficient
      cells, the deleterious effects of W447A mutation were greatly exacerbated,
      resulting in further attenuation of NO and greatly increased superoxide
      production. eNOS dimerization was attenuated in W447A eNOS cells and further
      reduced in BH4-deficient cells, as demonstrated using a novel split Renilla
      luciferase biosensor. Reduction of cellular BH4 levels resulted in a switch from
      an eNOS dimer to an eNOS monomer. These data reveal a key role for Trp-447 in
      determining NO versus superoxide production by eNOS, by effects on BH4-dependent
      catalysis, and by modulating eNOS dimer formation. 

PMID- 23965990
TI  - Effect of charged residues in the N-domain of Sup35 protein on prion [PSI+]
      stability and propagation.
AB  - Recent studies have shown that Sup35p prion fibrils probably have a parallel in
      register beta-structure. However, the part(s) of the N-domain critical for fibril
      formation and maintenance of the [PSI(+)] phenotype remains unclear. Here we
      designed a set of five SUP35 mutant alleles (sup35(KK)) with lysine substitutions
      in each of five N-domain repeats, and investigated their effect on infectivity
      and ability of corresponding proteins to aggregate and coaggregate with wild type
      Sup35p in the [PSI(+)] strain. Alleles sup35-M1 (Y46K/Q47K) and sup35-M2
      (Q61K/Q62K) led to prion loss, whereas sup35-M3 (Q70K/Q71K), sup35-M4
      (Q80K/Q81K), and sup35-M5 (Q89K/Q90K) were able to maintain the [PSI(+)] prion.
      This suggests that the critical part of the parallel in-register beta-structure
      for the studied [PSI(+)] prion variant lies in the first 63-69 residues. Our
      study also reveals an unexpected interplay between the wild type Sup35p and
      proteins expressed from the sup35(KK) alleles during prionization. Both Sup35-M1p
      and Sup35-M2p coaggregated with Sup35p, but only sup35-M2 led to prion loss in a
      dominant manner. We suggest that in the fibrils, Sup35p can bind to Sup35-M1p in
      the same conformation, whereas Sup35-M2p only allowed the Sup35p conformation
      that leads to the non-heritable fold. Mutations sup35-M4 and sup35-M5 influence
      the structure of the prion forming region to a lesser extent, and can lead to the
      formation of new prion variants. 

PMID- 23965991
TI  - Recruitment of a cytoplasmic chaperone relay by the A2A adenosine receptor.
AB  - The adenosine A2A receptor is a prototypical rhodopsin-like G protein-coupled
      receptor but has several unique structural features, in particular a long C
      terminus (of >120 residues) devoid of a palmitoylation site. It is known to
      interact with several accessory proteins other than those canonically involved in
      signaling. However, it is evident that many more proteins must interact with the
      A2A receptor, if the trafficking trajectory of the receptor is taken into account
      from its site of synthesis in the endoplasmic reticulum (ER) to its disposal by
      the lysosome. Affinity-tagged versions of the A2A receptor were expressed in
      HEK293 cells to identify interacting partners residing in the ER by a proteomics
      approach based on tandem affinity purification. The receptor-protein complexes
      were purified in quantities sufficient for analysis by mass spectrometry. We
      identified molecular chaperones (heat-shock proteins HSP90alpha and HSP70-1A)
      that interact with and retain partially folded A2A receptor prior to ER exit.
      Complex formation between the A2A receptor and HSP90alpha (but not HSP90beta) and
      HSP70-1A was confirmed by co-affinity precipitation. HSP90 inhibitors also
      enhanced surface expression of the receptor in PC12 cells, which endogenously
      express the A2A receptor. Finally, proteins of the HSP relay machinery (e.g.
      HOP/HSC70-HSP90 organizing protein and P23/HSP90 co-chaperone) were recovered in
      complexes with the A2A receptor. These observations are consistent with the
      proposed chaperone/coat protein complex II exchange model. This posits that
      cytosolic HSP proteins are sequentially recruited to folding intermediates of the
      A2A receptor. Release of HSP90 is required prior to recruitment of coat protein
      complex II components. This prevents premature ER export of partially folded
      receptors. 

PMID- 23965992
TI  - Cross-talk from beta-adrenergic receptors modulates alpha2A-adrenergic receptor
      endocytosis in sympathetic neurons via protein kinase A and spinophilin.
AB  - Inter-regulation of adrenergic receptors (ARs) via cross-talk is a long
      appreciated but mechanistically unclear physiological phenomenon. Evidence from
      the AR literature and our own extensive studies on regulation of alpha2AARs by
      the scaffolding protein spinophilin have illuminated a potential novel mechanism
      for cross-talk from beta to alpha2ARs. In the present study, we have
      characterized a mode of endogenous AR cross-talk in native adrenergic neurons
      whereby canonical betaAR-mediated signaling modulates spinophilin-regulated
      alpha2AAR endocytosis through PKA. Our findings demonstrate that co-activation of
      beta and alpha2AARs, either by application of endogenous agonist or by
      simultaneous stimulation with distinct selective agonists, results in
      acceleration of endogenous alpha2AAR endocytosis in native neurons. We show that
      receptor-independent PKA activation by forskolin is sufficient to accelerate
      alpha2AAR endocytosis and that alpha2AAR stimulation alone drives accelerated
      endocytosis in spinophilin-null neurons. Endocytic response acceleration by
      beta/alpha2AAR co-activation is blocked by PKA inhibition and lost in spinophilin
      null neurons, consistent with our previous finding that spinophilin is a
      substrate for phosphorylation by PKA that disrupts its interaction with
      alpha2AARs. Importantly, we show that alpha2AR agonist-mediated
      alpha2AAR/spinophilin interaction is blocked by betaAR co-activation in a PKA
      dependent fashion. We therefore propose a novel mechanism for cross-talk from
      beta to alpha2ARs, whereby canonical betaAR-mediated signaling coupled to PKA
      activation results in phosphorylation of spinophilin, disrupting its interaction
      with alpha2AARs and accelerating alpha2AAR endocytic responses. This mechanism of
      cross-talk has significant implications for endogenous adrenergic physiology and
      for therapeutic targeting of beta and alpha2AARs. 

PMID- 23965993
TI  - Recruitment of the Mint3 adaptor is necessary for export of the amyloid precursor
      protein (APP) from the Golgi complex.
AB  - The amyloid precursor protein (APP) is a ubiquitously expressed single-pass
      transmembrane protein that undergoes proteolytic processing by secretases to
      generate the pathogenic amyloid-beta peptide, the major component in Alzheimer
      plaques. The traffic of APP through the cell determines its exposure to
      secretases and consequently the cleavages that generate the pathogenic or
      nonpathogenic peptide fragments. Despite the likely importance of APP traffic to
      Alzheimer disease, we still lack clear models for the routing and regulation of
      APP in cells. Like the traffic of most transmembrane proteins, the binding of
      adaptors to its cytoplasmic tail, which is 47 residues long and contains at least
      four distinct sorting motifs, regulates that of APP. We tested each of these for
      effects on the traffic of APP from the Golgi by mutating key residues within them
      and examining adaptor recruitment at the Golgi and traffic to post-Golgi site(s).
      We demonstrate strict specificity for recruitment of the Mint3 adaptor by APP at
      the Golgi, a critical role for Tyr-682 (within the YENPTY motif) in Mint3
      recruitment and export of APP from the Golgi, and we identify LAMP1(+) structures
      as the proximal destination of APP after leaving the Golgi. Together, these data
      provide a detailed view of the first sorting step in its route to the cell
      surface and processing by secretases and further highlight the critical role
      played by Mint3. 

PMID- 23965994
TI  - Constant enthalpy change value during pyrophosphate hydrolysis within the
      physiological limits of NaCl.
AB  - A decrease in water activity was thought to result in smaller enthalpy change
      values during PPi hydrolysis, indicating the importance of solvation for the
      reaction. However, the physiological significance of this phenomenon is unknown.
      Here, we combined biochemistry and calorimetry to solve this problem using NaCl,
      a physiologically occurring water activity-reducing reagent. The pyrophosphatase
      activities of extremely halophilic Haloarcula japonica, which can grow at ~4 M
      NaCl, and non-halophilic Escherichia coli and Saccharomyces cerevisiae were
      maximal at 2.0 and 0.1 M NaCl, respectively. Thus, halophilic and non-halophilic
      pyrophosphatases exhibit distinct maximal activities at different NaCl
      concentration ranges. Upon calorimetry, the same exothermic enthalpy change of 
      35 kJ/mol was obtained for the halophile and non-halophiles at 1.5-4.0 and 0.1
      2.0 M NaCl, respectively. These results show that solvation changes caused by up
      to 4.0 M NaCl (water activity of ~0.84) do not affect the enthalpy change in PPi
      hydrolysis. It has been postulated that PPi is an ATP analog, having a so-called
      high energy phosphate bond, and that the hydrolysis of both compounds is
      enthalpically driven. Therefore, our results indicate that the hydrolysis of high
      energy phosphate compounds, which are responsible for biological energy
      conversion, is enthalpically driven within the physiological limits of NaCl.

PMID- 23965995
TI  - The ATP costs and time required to degrade ubiquitinated proteins by the 26 S
      proteasome.
AB  - The degradation of ubiquitinated proteins by 26 S proteasomes requires ATP
      hydrolysis. To investigate if the six proteasomal ATPases function independently
      or in a cyclic manner, as proposed recently, we used yeast mutants that prevent
      ATP binding to Rpt3, Rpt5, or Rpt6. Although proteasomes contain six ATPase
      subunits, each of these single mutations caused a 66% reduction in basal ATP
      hydrolysis, and each blocked completely the 2-3-fold stimulation of ATPase
      activity induced by ubiquitinated substrates. Therefore, the ATPase subunits must
      function in a ordered manner, in which each is required for the stimulation of
      ATPase activity by substrates. Although ATP is essential for multiple steps in
      proteasome function, when the rate of ATP hydrolysis was reduced incrementally,
      the degradation of Ub5-DHFR (where Ub is ubiquitin and DHFR is dihydrofolate
      reductase) decreased exactly in parallel. This direct proportionality implies
      that a specific number of ATPs is consumed in degrading a ubiquitinated protein.
      When the ubiquitinated DHFR was more tightly folded (upon addition of the ligand
      folate), the rate of ATP hydrolysis was unchanged, but the time to degrade a Ub5
      DHFR molecule (~13 s) and the energy expenditure (50-80 ATPs/Ub5-DHFR) both
      increased by 2-fold. With a mutation in the ATPase C terminus that reduced gate
      opening into the 20 S proteasome, the energy costs and time required for
      conjugate degradation also increased. Thus, different ubiquitin conjugates
      activate similarly the ATPase subunit cycle that drives proteolysis, but
      polypeptide structure determines the time required for degradation and thus the
      energy cost. 

PMID- 23965996
TI  - Coarse architecture of the transient receptor potential vanilloid 1 (TRPV1) ion
      channel determined by fluorescence resonance energy transfer.
AB  - The transient receptor potential vanilloid 1 ion channel is responsible for the
      perception of high temperatures and low extracellular pH, and it is also involved
      in the response to some pungent compounds. Importantly, it is also associated
      with the perception of pain and noxious stimuli. Here, we attempt to discern the
      molecular organization and location of the N and C termini of the transient
      receptor potential vanilloid 1 ion channel by measuring FRET between genetically
      attached enhanced yellow and cyan fluorescent protein to the N or C terminus of
      the channel protein, expressed in transfected HEK 293 cells or Xenopus laevis
      oocytes. The static measurements of the domain organization were mapped into an
      available cryo-electron microscopy density of the channel with good agreement.
      These measurements also provide novel insights into the organization of terminal
      domains and their proximity to the plasma membrane. 

PMID- 23965997
TI  - Structure of the type IVa major pilin from the electrically conductive bacterial
      nanowires of Geobacter sulfurreducens.
AB  - Several species of delta proteobacteria are capable of reducing insoluble metal
      oxides as well as other extracellular electron acceptors. These bacteria play a
      critical role in the cycling of minerals in subsurface environments, sediments,
      and groundwater. In some species of bacteria such as Geobacter sulfurreducens,
      the transport of electrons is proposed to be facilitated by filamentous fibers
      that are referred to as bacterial nanowires. These nanowires are polymeric
      assemblies of proteins belonging to the type IVa family of pilin proteins and are
      mainly comprised of one subunit protein, PilA. Here, we report the high
      resolution solution NMR structure of the PilA protein from G. sulfurreducens
      determined in detergent micelles. The protein is >85% alpha-helical and exhibits
      similar architecture to the N-terminal regions of other non-conductive type IVa
      pilins. The detergent micelle interacts with the first 21 amino acids of the
      protein, indicating that this region likely associates with the bacterial inner
      membrane prior to fiber formation. A model of the G. sulfurreducens pilus fiber
      is proposed based on docking of this structure into the fiber model of the type
      IVa pilin from Neisseria gonorrhoeae. This model provides insight into the
      organization of aromatic amino acids that are important for electrical
      conduction. 

PMID- 23965998
TI  - Translesion synthesis of 8,5'-cyclopurine-2'-deoxynucleosides by DNA polymerases
      eta, iota, and zeta.
AB  - Reactive oxygen species can give rise to a battery of DNA damage products
      including the 8,5'-cyclo-2'-deoxyadenosine (cdA) and 8,5'-cyclo-2'-deoxyguanosine
      (cdG) tandem lesions. The 8,5'-cyclopurine-2'-deoxynucleosides are quite stable
      lesions and are valid and reliable markers of oxidative DNA damage. However, it
      remains unclear how these lesions compromise DNA replication in mammalian cells.
      Previous in vitro biochemical assays have suggested a role for human polymerase
      (Pol) eta in the insertion step of translesion synthesis (TLS) across the (5'S)
      diastereomers of cdA and cdG. Using in vitro steady-state kinetic assay, herein
      we showed that human Pol iota and a two-subunit yeast Pol zeta complex
      (REV3/REV7) could function efficiently in the insertion and extension steps,
      respectively, of TLS across S-cdA and S-cdG; human Pol kappa and Pol eta could
      also extend past these lesions, albeit much less efficiently. Results from a
      quantitative TLS assay showed that, in human cells, S-cdA and S-cdG inhibited
      strongly DNA replication and induced substantial frequencies of mutations at the
      lesion sites. Additionally, Pol eta, Pol iota, and Pol zeta, but not Pol kappa,
      had important roles in promoting replication through S-cdA and S-cdG in human
      cells. Based on these results, we propose a model for TLS across S-cdA and S-cdG
      in human cells, where Pol eta and/or Pol iota carries out nucleotide insertion
      opposite the lesion, whereas Pol zeta executes the extension step. 

PMID- 23965999
TI  - Duplication and functional specialization of the telomere-capping protein Cdc13
      in Candida species.
AB  - The budding yeast G-tail binding complex CST (Cdc13-Stn1-Ten1) is crucial for
      both telomere protection and replication. Previous studies revealed a family of
      Cdc13 orthologues (Cdc13A) in Candida species that are unusually small but are
      nevertheless responsible for G-tail binding and the regulation of telomere
      lengths and structures. Here we report the identification and characterization of
      a second family of Cdc13-like proteins in the Candida clade, named Cdc13B.
      Phylogenetic analysis and sequence alignment indicate that Cdc13B probably arose
      through gene duplication prior to Candida speciation. Like Cdc13A, Cdc13B appears
      to be essential. Deleting one copy each of the CDC13A and CDC13B genes caused a
      synergistic effect on aberrant telomere elongation and t-circle accumulation,
      suggesting that the two paralogues mediate overlapping and nonredundant functions
      in telomere regulation. Interestingly, Cdc13B utilizes its C-terminal OB-fold
      domain (OB4) to mediate self-association and binding to Cdc13A. Moreover, the
      stability of the heterodimer is evidently greater than that of either homodimer.
      Both the Cdc13 A/A homodimer and A/B heterodimer, but not the B/B homodimer,
      recognized the telomere G-tail repeat with high affinity and sequence
      specificity. Our results reveal novel evolutionary elaborations of the G-tail
      binding protein in Saccharomycotina yeast, suggesting a drastic remodeling of
      CDC13 that entails gene duplication, fusion, and functional specialization. The
      repeated and independent duplication of G-tail-binding proteins such as Cdc13 and
      Pot1 hints at the evolutionary advantage of having multiple G-tail-binding
      proteins. 

PMID- 23966001
TI  - Tools for improving cats' lives worldwide.

PMID- 23966000
TI  - An isoform of C/EBPbeta, LIP, regulates expression of the chemokine receptor
      CXCR4 and modulates breast cancer cell migration.
AB  - Metastasis is the primary cause of death in cancer patients. CXCR4/CXCL12
      chemokine axis provides directional cues for breast cancer cells to metastasize
      to specific organs. Despite their potential clinical importance, how CXCR4
      expression in breast cancer cells is regulated at the molecular level is not well
      understood. We identified an isoform of C/EBPbeta, liver-enriched inhibitory
      protein (LIP), as a previously unrecognized transcriptional regulator of CXCR4 in
      breast cancer cells. LIP up-regulated the transcription of CXCR4 through direct
      interaction with the CXCR4 promoter. The increase in CXCR4 mRNA was paralleled by
      an increased cell surface expression of the CXCR4, which in turn promoted CXCR4
      mediated breast cancer cell migration. A significant positive correlation between
      LIP and CXCR4 expression was observed in stage III and IV human breast carcinoma
      specimens. Neuregulin 1 (or NRG1, hereafter referred to as heregulin) increased
      CXCR4 expression in breast cancer cells, and this coincided with increased LIP
      binding on the CXCR4 promoter. These findings may have important implications for
      understanding the molecular basis of CXCR4-mediated breast cancer cell metastasis
      and could potentially allow us to develop novel strategies to reduce morbidity
      and mortality in patients with metastatic breast cancer. 

PMID- 23966002
TI  - What is a feral cat?: Variation in definitions may be associated with different
      management strategies.
AB  - STUDY RATIONALE: The definition of a true feral cat is an area of much
      contention, with many variations used worldwide. In this study, opinions were
      gathered from feral cat rescue workers and veterinary surgeons working in the
      United Kingdom to identify a practical definition of a feral cat, suitable for
      use in the field, education and research. PROTOCOL: A mixed methods approach,
      using questionnaires and focus groups, was used to collect data from feral cat
      workers and veterinary surgeons. FINDINGS: Conflicts in opinion on the
      implications of taming feral cats exist. The rescue workers typically felt that
      most cats could be tamed, whereas the veterinary surgeons felt this was generally
      inappropriate, except in the case of young kittens. A consistent definition of
      feral cats would enable better communication regarding the welfare and management
      of these animals, and would be useful for further research and education of the
      public. PROPOSED DEFINITION: A feral cat is proposed by this study to be a cat
      that is unapproachable in its free-roaming environment and is capable of
      surviving with or without direct human intervention, and may additionally show
      fearful or defensive behaviour on human contact.

PMID- 23966003
TI  - More than just T4: diagnostic testing for hyperthyroidism in cats.
AB  - CLINICAL CHALLENGES: In older cats presenting with clinical features of
      hyperthyroidism, confirmation of a diagnosis of thyroid disease is usually
      straightforward. However, the potential for false-negative and false-positive
      results exists with all thyroid function tests (especially in the context of
      routine screening of asymptomatic cats) and leads to clinical dilemmas. For
      example, a high serum T4 value may be found in a cat that lacks clinical signs of
      hyperthyroidism, or hyperthyroidism may be suspected in a cat with normal total
      T4 concentrations. PRACTICAL RELEVANCE: To avoid unnecessary treatment and
      potentially adverse effects in a euthyroid cat, thyroid function tests must
      always be interpreted in the light of the cat's history, clinical signs, physical
      examination findings and other laboratory findings. EVIDENCE BASE: In this
      article the author reviews the use of commonly recommended thyroid function
      tests, focusing on clinical scenarios that present diagnostic difficulties. In
      doing so, he draws on the veterinary and comparative literature, his own clinical
      experience, and data, unpublished to date, obtained from a series of 100
      hyperthyroid cats consecutively diagnosed at his clinic.

PMID- 23966004
TI  - Feline non-flea induced hypersensitivity dermatitis: clinical features, diagnosis
      and treatment.
AB  - PRACTICAL RELEVANCE: Hypersensitivity dermatitis (HD) is often suspected in cats
      and is mostly caused by insect bites, food or environmental allergens. Cats with
      non-flea induced HD are reported to present frequently with one or more of the
      following cutaneous reaction patterns: miliary dermatitis, eosinophilic
      dermatitis, self-induced symmetrical alopecia or head and neck
      excoriations/pruritus. CLINICAL CHALLENGES: None of the above patterns are,
      however, pathognomonic for non-flea induced HD and the diagnosis of this
      condition is based on exclusion of diseases presenting similarly and an adequate
      response to treatment. Therapeutic approaches to affected cats include use of
      immunomodulatory drugs (ciclosporin, glucocorticoids, antihistamines),
      hypoallergenic diets and allergen-specific immunotherapy. EVIDENCE BASE: This
      review provides an update on the clinical signs, diagnosis and treatment of
      feline non-flea induced HD. It draws on the findings of a recent large-scale
      study that described the clinical signs of numerous cats with non-flea HD and has
      proposed criteria to facilitate the diagnosis of the condition.

PMID- 23966005
TI  - 2013 AAFP Feline Vaccination Advisory Panel Report.
AB  - RATIONALE: This Report was developed by the Feline Vaccination Advisory Panel of
      the American Association of Feline Practitioners (AAFP) to provide practical
      recommendations to help clinicians select appropriate vaccination schedules for
      their feline patients based on risk assessment. The recommendations rely on
      published data as much as possible, as well as consensus of a multidisciplinary
      panel of experts in immunology, infectious disease, internal medicine and
      clinical practice.

PMID- 23966006
TI  - ISFM guidelines on population management and welfare of unowned domestic cats
      (Felis catus).
AB  - GUIDELINES RATIONALE: Cats are among the most commonly kept domestic pets, and
      coexist with humans in a variety of different circumstances. Cats are sentient
      beings and, as such, humans have a responsibility for cat welfare where humans
      and cats coexist. Because cats reproduce efficiently, measures to control
      populations are frequently needed, but these should be based on ethical and
      humane approaches. FRAMEWORK: These consensus guidelines from the International
      Society of Feline Medicine's Welfare Advisory Panel provide a framework for the
      approach to welfare and population control measures, primarily among unowned cats
      and those going through a homing programme.

PMID- 23966008
TI  - Use of pheromones to reduce stress in sheltered cats.

PMID- 23966009
TI  - Re-shedding of Toxoplasma gondii oocysts.

PMID- 23966011
TI  - A case of meconium aspiration syndrome in a bottlenose dolphin (Tursiops
      truncatus) calf.
AB  - Stillbirth and neonatal mortality are significant problems in captive breeding of
      dolphins, however, the causes of these problems are not fully understood. Here,
      we report a case of meconium aspiration syndrome (MAS) in a male neonate of
      bottlenose dolphin (Tursiops truncates) who died immediately after birth. At
      necropsy, a true knot was found in the umbilical cord. The lungs showed diffuse
      intraalveolar edema, hyperemic congestion and atelectasis due to meconium
      aspiration with mild inflammatory cell infiltration. Although the exact cause of
      MAS in this case was unknown, fetal hypoxia due possibly to the umbilical knot
      might have been associated with MAS, which is the first report in dolphins. MAS
      due to perinatal asphyxia should be taken into account as a possible cause of
      neonatal mortality and stillbirth of dolphin calves. 

PMID- 23966013
TI  - [Cone beam computed tomography in endodontics: a review for daily clinical
      practice].
AB  - Since the introduction of cone beam computed tomography (CBCT), this 3
      dimensional diagnostic imaging technique has been established in a growing number
      of fields in dental medicine. It has become an important tool for both diagnosis
      and treatment planning, and is also able to support endodontic treatments.
      However, the higher effective dose of ionizing radiation compared to conventional
      2-dimensional radiographs is not justifiable in every case. CBCT allows for a
      more precise diagnosis of periapical lesions, root fractures as well as external
      and internal resorptions. Concerning the utility of CBCT in treatment planning
      decisions, the gain of information through 3-dimensional imaging for any of these
      pathologies has to be evaluated carefully on an individual basis. Moreover,
      radioopaque materials such as root canal filling and posts often create
      artefacts, which may compromise diagnosis. The aim of this review is to summarize
      the possibilities and limits of CBCT imaging in endodontology as well as
      introduce guidelines for daily clinical practice. Furthermore, the article
      presents possible therapeutic advantages of preexisting CBCT scans for root canal
      treatments. 

PMID- 23966014
TI  - Higher impact, wider influence.

PMID- 23966012
TI  - Pathogenesis of Newcastle disease in vaccinated chickens: pathogenicity of
      isolated virus and vaccine effect on challenge of its virus.
AB  - The pathogenicity of Newcastle disease (ND) virus, isolated from ND outbreak in
      vaccinated chickens, was evaluated through experiments. The pathogenicity indexes
      (mean death time (MDT); 58 hr, intracerebral pathogenicity index (ICPI); 1.7 and
      intravenous pathogenicity index (IVPI); 2.51) indicated that the ND virus was
      velogenic. The ND virus caused lymphocytic necrosis in the spleen with fibrinous
      exudation and proliferation of macrophages, sinusoidal fibrin exudation in the
      liver, proliferation of macrophages in the lung, lymphocytic necrosis and
      depletion in the bursa of Fabricius, cecal tonsils and thymus, necrosis of bone
      marrow, tracheitis, conjunctivitis and necrosis of feather epithelial cells in
      specific-pathogen-free chickens. Immunohistochemically, ND virus antigens were
      seen in the lesions mentioned above. The ND virus could not induce the
      encephalitis and pancreatitis that were observed in the natural case of ND in
      vaccinated chickens. There was no clinical disease in vaccinated chickens after
      the challenge of the ND virus. In diluted ND vaccine experiments, chickens
      vaccinated with a high dilution of vaccine and then challenged with the ND virus
      showed clinical sign and mortality with pancreatic focal necrosis. Vaccine
      diluted with fresh tap water had no effect on protection against the challenge of
      the ND virus. This study suggests that improper vaccination may be involved in
      outbreaks of ND in vaccinated chickens. 

PMID- 23966015
TI  - Inhibition of hepatic fibrosis with artificial microRNA using ultrasound and
      cationic liposome-bearing microbubbles.
AB  - We sought to investigate the antifibrotic effects of an artificial microRNA
      (miRNA) targeting connective tissue growth factor (CTGF) using the ultrasound
      targeted cationic liposome-bearing microbubble destruction gene delivery system.
      Cationic liposomes were conjugated with microbubbles using a biotin-avidin
      system. Plasmids carrying the most effective artificial miRNA sequences were
      delivered by ultrasound-targeted cationic liposome-bearing microbubble
      destruction gene delivery system to rats with hepatic fibrosis. The results show
      that this method of gene delivery effectively transported the plasmids to the rat
      liver. The artificial miRNA reduced hepatic fibrosis pathological alterations as
      well as the protein and mRNA expressions of CTGF and transforming growth factor
      beta1. Furthermore, the CTGF gene silencing decreased the levels of type I
      collagen and alpha-smooth muscle actin (P<0.01). These data suggest that delivery
      of an artificial miRNA targeted against CTGF using ultrasound-targeted cationic
      liposome-bearing microbubble destruction may be an efficacious therapeutic method
      to ameliorate hepatic fibrosis. 

PMID- 23966016
TI  - Novel bunyavirus in domestic and captive farmed animals, Minnesota, USA.
AB  - We tested blood samples from domestic and captive farmed animals in Minnesota,
      USA, to determine exposure to severe fever with thrombocytopenia syndrome virus
      and Heartland-like virus. We found antibodies against virus nucleoproteins in 10%
      18% of samples from cattle, sheep, goats, deer, and elk in 24 Minnesota counties.

PMID- 23966017
TI  - Design and simulation of a full-ring multi-lofthole collimator for brain SPECT.
AB  - Currently, clinical brain single photon emission computed tomography (SPECT) is
      mostly performed using rotating dual-head gamma cameras equipped with low-energy
      high-resolution parallel-beam collimators (LEHR PAR). The resolution of these
      systems is rather poor (8-10 mm) and the rotation of the heavy gamma cameras can
      introduce misalignment errors. Therefore, we designed a static full-ring multi
      lofthole brain SPECT insert for an existing ring of LaBr3 (5% Ce) detectors. The
      novelty of the design is found in the shutter mechanism that makes the system
      very flexible and eliminates the need for rotating parts. A stationary SPECT
      insert is not only more robust, it is also easier to integrate in a magnetic
      resonance imaging system (MRI) for simultaneous SPECT-MRI. The target spatial
      resolution of our design is 6 mm. In this study we used analytical calculations
      to optimize the collimator for an existing ring of LaBr3 (5% Ce) detectors. We
      fixed the target spatial resolution at 6 mm in the center of the field-of-view
      and maximized the volume sensitivity by changing the collimator radius, the
      aperture and the number of loftholes. Based on these optimal parameters we
      simulated phantom data and evaluated the image quality of our multi-lofthole
      system. We simulated a noiseless uniform and Defrise phantom to assess artifacts
      and sampling completeness and a noiseless hot-rod phantom to assess the
      reconstructed spatial resolution. We visually evaluated a simulated noisy Hoffman
      phantom with two lesions. Then, we evaluated the non-prewhitening matched filter
      signal-to-noise ratio (NPW-SNR) in two lesion detectability phantoms: one with
      hot lesions and one with cold lesions. Finally, a contrast-to-noise (CNR) study
      was performed on a phantom with both hot and cold lesions of different sizes (6
      16 mm). All results were compared to a LEHR PAR system. The optimization resulted
      in a final collimator design with a volume sensitivity of 1.55 * 10(-4) cps Bq(
      1), which is 2.5 times lower than the sensitivity of a dual-head system with LEHR
      PAR collimators. Spatial resolution, on the other hand, has clearly improved
      compared to LEHR PAR: with the multi-lofthole system we successfully
      reconstructed 4 mm hot rods. Although this improved resolution did not result in
      an unambiguous improvement in CNR or NPW-SNR, we believe that the flexibility of
      the shutter mechanism opens interesting perspectives toward time-multiplexing and
      integration with MRI. 

PMID- 23966018
TI  - Effects of balance strategy training in myasthenia gravis: a case study series.
AB  - INTRODUCTION: Studies of exercise in patients with myasthenia gravis (MG) are
      sparse. Balance strategy training (BST) multimodal exercise has proven efficacy
      in adults for enhancing balance and functional mobility. This prospective study
      aims to determine if BST improves functional ability and balance in people with
      MG. METHODS: Seven individuals with MG participated in a 16-session workstation
      intervention. Repeated measures (pre/post-intervention and 4-week follow-up)
      consisting of quantitative myasthenia gravis score (QMG), 6-minute walk test
      (6MWT), timed up and go (TUG) with dual task (TUG(manual) and TUG(cognitive)),
      and standing stability on foam with eyes closed (foamEC) were assessed. RESULTS:
      Most measurements showed sustained improvement at follow-up. QMG, TUG(cognitive),
      and foam EC achieved clinically significant improvements (>15%). No adverse
      effects were reported. CONCLUSIONS: BST was effective in improving balance and
      QMG scores in subjects with MG. A multimodal BST approach is thus suggested to
      target different aspects of balance and functional mobility.

PMID- 23966019
TI  - Studies on CD36 deficiency in South China: Two cases demonstrating the clinical
      impact of anti-CD36 antibodies.
AB  - CD36 (also known as GPIV) deficiency is known to be responsible for the
      production of anti-Nak(a) antibodies in different clinical settings such as
      fetal/neonatal alloimmune thrombocytopenia (FNAIT), platelet transfusion
      refractoriness (PTR) and post-transfusion purpura (PTP). However, no data
      regarding the relevance of CD36 immunisation is currently available for China. In
      this study, healthy blood donors were typed for CD36 deficiency using flow
      cytometry. Nucleotide sequencing was performed to identify the molecular basis
      underlying the CD36 deficiency. Anti-Nak(a) antibodies in CD36-deficient
      individuals were analysed by ELISA and flow cytometry. By analysis of 998 healthy
      blood donors, 18 individuals failed to express CD36 on their platelets. In 5/12
      individuals no CD36 expression was detected both on platelets and monocytes. This
      result suggested that the frequencies of type I CD36 deficiency (platelets and
      monocytes) and type II CD36 deficiency (platelets only) are approximately 0.5 and
      1.3%, respectively. Nucleotide sequencing analysis of type I CD36 deficient
      individuals revealed eight different mutations; four of them were not described
      so far. However, 1228-1239del ATTGTGCCTATT and 329-330delAC appear to be the most
      common mutations related to type I CD36 deficiency in South Chinese population.
      Further analysis showed that 1/5 type I CD36 deficient individuals developed anti
      Nak(a) antibodies. In addition, anti-Nak(a) antibodies could be identified in two
      cases of thrombocytopenia associated with FNAIT and PTR. In conclusion, more than
      0.5% of CD36 type I-deficient individuals are at risk to be immunised through
      blood transfusion or pregnancy in China. Testing of anti-Nak(a) antibodies should
      be considered in FNAIT and PTR suspected cases. A registry of CD36-deficient
      donors should be established to allow treatment of immune-mediated bleeding
      disorders caused by anti-Nak(a) antibodies.

PMID- 23966021
TI  - Roles of YehZ, a putative osmoprotectant transporter, in tempering growth of
      Salmonella enterica serovar Typhimurium.
AB  - Salmonella, a main cause of foodborne diseases, encounters a variety of
      environmental stresses and overcomes the stresses by multiple resistance
      strategies. One of the general responses to hyperosmotic stress is to import or
      produce compatible solutes so that cells maintain fluid balance and protect
      proteins and lipids from denaturation. The ProP and ProU systems are the main
      transport systems for compatible solutes. The OsmU system, recently identified as
      a third osmoprotectant transport system, debilitates excessive growth as well by
      reducing production of trehalose. We studied a fourth putative osmoprotectant
      transport system, YehZYXW, with high sequence similarity with the OsmU system. A
      Salmonella strain lacking YehZ, a predicted substrate-binding protein, did not
      suffer from hyperosmolarity but rather grew more rapidly than the wild type
      regardless of glycine betaine, an osmoprotectant, suggesting that the YehZYXW
      system controls bacterial growth irrespective of transporting glycine betaine.
      However, the growth advantage of DeltayehZ was not attributable to an increase in
      OtsBA-mediated trehalose production, which is responsible for the outcompetition
      of the DeltaosmU strain. Overexpressed YehZ in trans was capable of
      deaccelerating bacterial growth vice versa, supporting a role of YehZ in
      dampening growth. The expression of yehZ was increased in response to nutrient
      starvation, acidic pH, and the presence of glycine betaine under hyperosmotic
      stress. Identifying substrates for YehZ will help decipher the role of the
      YehZYXW system in regulating bacterial growth in response to environmental cues.

PMID- 23966020
TI  - Isolation and characterization of a novel agar-degrading marine bacterium,
      Gayadomonas joobiniege gen, nov, sp. nov., from the Southern Sea, Korea.
AB  - An agar-degrading bacterium, designated as strain G7(T), was isolated from a
      coastal seawater sample from Gaya Island (Gayado in Korean), Republic of Korea.
      The isolated strain G7(T) is gram-negative, rod shaped, aerobic, non-motile, and
      non-pigmented. A similarity search based on its 16S rRNA gene sequence revealed
      that it shares 95.5%, 90.6%, and 90.0% similarity with the 16S rRNA gene
      sequences of Catenovulum agarivorans YM01(T), Algicola sagamiensis, and
      Bowmanella pacifica W3-3A(T), respectively. Phylogenetic analyses demonstrated
      that strain G7(T) formed a distinct monophyletic clade closely related to species
      of the family Alteromonadaceae in the Alteromonas-like Gammaproteobacteria. The
      G+C content of strain G7(T) was 41.12 mol%. The DNA-DNA hybridization value
      between strain G7(T) and the phylogenetically closest strain YM01(T) was 19.63%.
      The genomes of G7(T) and YM01(T) had an average ANIb value of 70.00%. The
      predominant isoprenoid quinone of this particular strain was ubiquinone-8,
      whereas that of C. agarivorans YM01(T) was menaquinone-7. The major fatty acids
      of strain G7(T) were Iso-C15:0(41.47%), Anteiso-C15:0(22.99%), and
      C16:1omega7c/iso-C15:02-OH (8.85%), which were quite different from those of
      YM01(T). Comparison of the phenotypic characteristics related to carbon
      utilization, enzyme production, and susceptibility to antibiotics also
      demonstrated that strain G7(T) is distinct from C. agarivorans YM01T. Based on
      its phenotypic, chemotaxonomic, and phylogenetic distinctiveness, strain G7(T)
      was considered a novel genus and species in the Gammaproteobacteria, for which
      the name Gayadomonas joobiniege gen. nov. sp. nov. (ATCC BAA-2321 = DSM25250(T) =
      KCTC23721(T)) is proposed.

PMID- 23966022
TI  - Epidemiological trends of sexually transmitted infections among women in Cheonan,
      South Korea, 2006-2012.
AB  - A lack of investigation in specific regions has impeded the understanding of
      epidemiological trends in the prevalence of sexually transmitted infections
      (STIs) in South Korea. To help fill this research gap, this study used multiplex
      polymerase chain reaction (mPCR) to determine the prevalence of STIs detected in
      clinical specimens collected from women in Cheonan, South Korea between August
      2006 and November 2012, and analyzed the prevalence of STIs according to age,
      bacterial pathogen, and time period. Of the 1,618 specimens collected from 1,523
      patients, 536 (35.2%) tested positive for at least 1 pathogen, with 407 (25.2%)
      testing positive for 1 pathogen, 103 (6.4%) for 2 pathogens, 20 (1.2%) for 3
      pathogens, and 6 (0.4%) for 4 pathogens (n = 697 pathogens total). The median
      ages of all patients and of STI-positive patients were 37.8 and 33.3 years,
      respectively, and both decreased annually over the study period. Mycoplasma
      hominis (MH) was detected in 62.1% of the positive specimens, Ureaplasma
      urealyticum (UU) in 28.4%, Chlamydia trachomatis (CT) in 23.1%, Trichomonas
      vaginalis (TV) in 7.8%, Mycoplasma genitalium (MG) in 6.5%, and Neisseria
      gonorrhoeae (NG) in 2.1%. Whereas the prevalence of MH, MG, and TV infection did
      not vary greatly over the study period, that of UU decreased by one-fifth and
      that of both CT and NG increased 4-fold. The results indicate great variability
      in the rates of infection with each pathogen and a decreasing trend in overall
      STI prevalence, age of patients seeking STI testing, and age of STI-positive
      patients. 

PMID- 23966024
TI  - Sumanenylferrocenes and their solid state self-assembly.
AB  - The first ferrocene-fused organometallic compounds derived from the buckybowl
      sumanene (C21H12) are presented. Both compounds, sumanenylferrocene and 1,1'
      disumanenylferrocene, have been synthesized by Negishi-type cross-coupling of
      iodosumanene and were studied crystallographically. Sumanenylferrocenes form
      unique packing motifs, which are both different from those of their corannulene
      congeners and sumanene itself. 

PMID- 23966025
TI  - Weight-based determination of spinal canal depth for paediatric lumbar punctures.
AB  - OBJECTIVES: The aim of this study was to evaluate whether spinal canal depth
      (SCD), measured using ultrasound, could be estimated from simple body
      measurements in a sample of children. METHODS: We measured SCD in a group of 225
      children aged 0-18 years in the curved left lateral position using ultrasound.
      Statistical analysis was performed using Pearson's correlation coefficient at the
      5% level of significance. We also performed linear regression analyses (analysis
      of variance) for mid-spinal canal depth (MSCD), including five potential
      predictors of age, gender, height, weight and body surface area, in each model.
      RESULTS: The mean MSCD was 33.0 mm (18.1-56.4) across the whole cohort. The best
      linear correlation of MSCD (mm) was found with weight (W; kg), approximating the
      formula MSCD=0.4W+20 (R(2)=0.72). Body weight accounted for 85% of the variance
      in the data (adjusted R(2)=0.72). Our formula gives values outside of the actual
      measured SCD range in 23/225 (10.2%) of cases and estimates MSCD at 24 mm at 10
      kg, 32 mm at 30 kg and 40 mm at 50 kg. CONCLUSIONS: We demonstrate a good
      correlation between weight and MSCD in a large group of children. Use of the
      simple formula MSCD (mm)=0.4 W+20 could improve the success rates of lumbar
      puncture in the paediatric population, but remains to be validated.

PMID- 23966023
TI  - Glutamate levels in the associative striatum before and after 4 weeks of
      antipsychotic treatment in first-episode psychosis: a longitudinal proton
      magnetic resonance spectroscopy study.
AB  - IMPORTANCE: Increased glutamate levels in the right associative striatum have
      been described in patients during a first episode of psychosis. Whether this
      increase would persist after effective antipsychotic treatment is unknown.
      OBJECTIVES: To compare the glutamate levels in antipsychotic-naive patients with
      first-episode psychosis in the right associative striatum and right cerebellar
      cortex using proton magnetic resonance spectroscopy before and 4 weeks after
      antipsychotic treatment and to compare these results with normative data from sex
      matched healthy control subjects. DESIGN, SETTING, AND PARTICIPANTS: Before-after
      trial in an inpatient psychiatric research unit among 24 antipsychotic-naive
      patients with first-episode psychosis and 18 healthy controls matched for age,
      sex, handedness, and cigarette smoking. INTERVENTIONS: Participants underwent 2
      proton magnetic resonance spectroscopy studies: patients were imaged at baseline
      and after 4 weeks of antipsychotic treatment, while controls were imaged at
      baseline and at 4 weeks after the baseline measurement. Patients were treated
      with oral risperidone (open label) for 4 weeks with dosages that were titrated on
      the basis of clinical judgment. MAIN OUTCOMES AND MEASURES: Glutamate levels were
      estimated using LCModel (version 6.2-1T) and were corrected for the cerebrospinal
      fluid proportion within the voxel. RESULTS: Patients with first-episode psychosis
      had higher levels of glutamate in the associative striatum and the cerebellum
      during the antipsychotic-naive condition compared with controls. After clinically
      effective antipsychotic treatment, glutamate levels significantly decreased in
      the associative striatum, with no significant change in the cerebellum. No
      differences in glutamate levels were observed between groups at 4 weeks.
      CONCLUSIONS AND RELEVANCE: Increased glutamate levels observed at baseline in
      patients with first-episode psychosis normalized after 4 weeks of clinically
      effective antipsychotic treatment. These results provide support for the
      hypothesis that improvement in clinical symptoms might be related to a decrease
      in glutamate levels.

PMID- 23966026
TI  - Enhanced quality and productivity of long-term aftercare of cancer in young
      people.
AB  - INTRODUCTION: Long-term morbidity associated with survival from childhood cancer
      is well defined. Traditional models of hospital-based long-term aftercare are not
      sustainable and may not be necessary for all. A programme to support development
      and implementation of redesigned care pathways is reported. METHOD: Application
      of service improvement methodologies to identify the case for change, to evidence
      development of, and test, new aftercare pathways. RESULTS: Four models of
      aftercare were identified; traditional cancer centre-delivered medical follow-up,
      shared care with local hospitals or primary care, specialist nurse-led supported
      management and self-management. Key components required for successful
      implementation of risk-stratified care included; comprehensive information
      transfer with treatment summaries and care plans, provision of care coordinators,
      effective transition across services, remote monitoring systems, educating
      professionals, maintaining patient choice. CONCLUSIONS: Adoption of risk
      stratified evidence-based aftercare pathways, generated through application of
      service improvement methodologies, can result in the delivery of enhanced quality
      and productivity.

PMID- 23966027
TI  - Just too many things to remember? A survey of paediatric trainees' recall of
      Advanced Paediatric Life Support (APLS) weight estimation formulae.

PMID- 23966028
TI  - Asthma: standards of care.

PMID- 23966029
TI  - Fibrous dysplasia causing safeguarding concerns.

PMID- 23966030
TI  - Ischaemic heart disease, influenza and influenza vaccination: a prospective case
      control study.
AB  - BACKGROUND: Abundant, indirect epidemiological evidence indicates that influenza
      contributes to all-cause mortality and cardiovascular hospitalisations with
      studies showing increases in acute myocardial infarction (AMI) and death during
      the influenza season. OBJECTIVE: To investigate whether influenza is a
      significant and unrecognised underlying precipitant of AMI. DESIGN: Case-control
      study. SETTING: Tertiary referral hospital in Sydney, Australia, during 2008 to
      2010. PATIENTS: Cases were inpatients with AMI and controls were outpatients
      without AMI at a hospital in Sydney, Australia. MAIN OUTCOME MEASURES: Primary
      outcome was laboratory evidence of influenza. Secondary outcome was baseline self
      reported acute respiratory tract infection. RESULTS: Of 559 participants, 34/275
      (12.4%) cases and 19/284 (6.7%) controls had influenza (OR 1.97, 95% CI 1.09 to
      3.54); half were vaccinated. None were recognised as having influenza during
      their clinical encounter. After adjustment, influenza infection was no longer a
      significant predictor of recent AMI. However, influenza vaccination was
      significantly protective (OR 0.55, 95% CI 0.35 to 0.85), with a vaccine
      effectiveness of 45% (95% CI 15% to 65%). CONCLUSIONS: Recent influenza infection
      was an unrecognised comorbidity in almost 10% of hospital patients. Influenza did
      not predict AMI, but vaccination was significantly protective but underused. The
      potential population health impact of influenza vaccination, particularly in the
      age group 50-64 years, who are at risk for AMI but not targeted for vaccination,
      should be further explored. Our data should inform vaccination policy and
      cardiologists should be aware of missed opportunities to vaccinate individuals
      with ischaemic heart disease against influenza.

PMID- 23966031
TI  - Evolution and distribution of saxitoxin biosynthesis in dinoflagellates.
AB  - Numerous species of marine dinoflagellates synthesize the potent environmental
      neurotoxic alkaloid, saxitoxin, the agent of the human illness, paralytic
      shellfish poisoning. In addition, certain freshwater species of cyanobacteria
      also synthesize the same toxic compound, with the biosynthetic pathway and genes
      responsible being recently reported. Three theories have been postulated to
      explain the origin of saxitoxin in dinoflagellates: The production of saxitoxin
      by co-cultured bacteria rather than the dinoflagellates themselves, convergent
      evolution within both dinoflagellates and bacteria and horizontal gene transfer
      between dinoflagellates and bacteria. The discovery of cyanobacterial saxitoxin
      homologs in dinoflagellates has enabled us for the first time to evaluate these
      theories. Here, we review the distribution of saxitoxin within the
      dinoflagellates and our knowledge of its genetic basis to determine the likely
      evolutionary origins of this potent neurotoxin. 

PMID- 23966032
TI  - The anticancer effect of fucoidan in PC-3 prostate cancer cells.
AB  - Fucoidan, a sulfated polysaccharide, has a variety of biological activities, such
      as anti-cancer, anti-angiogenic and anti-inflammatory. However, the mechanisms of
      action of fucoidan as an anti-cancer agent have not been fully elucidated. The
      present study examined the anti-cancer effect of fucoidan obtained from Undaria
      pinnatifida in PC-3 cells, human prostate cancer cells. Fucoidan induced the
      apoptosis of PC-3 cells by activating both intrinsic and extrinsic pathways. The
      induction of apoptosis was accompanied by the activation of extracellular signal
      regulated kinase mitogen-activated protein kinase (ERK1/2 MAPK) and the
      inactivation of p38 MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt. In
      addition, fucoidan also induced the up-regulation of p21Cip1/Waf and down
      regulation of E2F-1 cell-cycle-related proteins. Furthermore, in the Wnt/beta
      catenin pathway, fucoidan activated GSK-3beta that resulted in the decrease of
      beta-catenin level, followed by the decrease of c-myc and cyclin D1 expressions,
      target genes of beta-catenin in PC-3 cells. These results suggested that fucoidan
      treatment could induce intrinsic and extrinsic apoptosis pathways via the
      activation of ERK1/2 MAPK, the inactivation of p38 MAPK and PI3K/Akt signaling
      pathway, and the down-regulation of Wnt/beta-catenin signaling pathway in PC-3
      prostate cancer cells. These data support that fucoidan might have potential for
      the treatment of prostate cancer. 

PMID- 23966033
TI  - Fucoidans as potential inhibitors of HIV-1.
AB  - The antiviral activity of different structure fucoidans (alpha-l-fucans and
      galactofucans) was studied using two model viral systems based on a lentiviral
      vectors and a replication competent Moloney murine leukemia virus (Mo-MuLV). It
      was found that investigated fucoidans have no cytotoxic effects on Jurkat and SC
      1cell at the concentration range of 0.001-100 ug/mL. Fucoidans with different
      efficiency suppressed transduction of Jurkat cell line by pseudo-HIV-1 particles
      carrying the envelope protein of HIV-1 and infection of SC-1 cells by Mo-MuLV.
      According to our data, all natural fucoidans can be considered as potential anti
      HIV agents regardless of their carbohydrate backbone and degree of sulfating,
      since their activity is shown at low concentrations (0.001-0.05 ug/mL). High
      molecular weight fucoidans isolated from Saccharina cichorioides (1.3-alpha-l
      fucan), and S. japonica (galactofucan) were the most effective inhibitors. 

PMID- 23966034
TI  - Bouillonamide: a mixed polyketide-peptide cytotoxin from the marine
      cyanobacterium Moorea bouillonii.
AB  - The tropical marine cyanobacterium, Moorea bouillonii, has gained recent
      attention as a rich source of bioactive natural products. Continued chemical
      investigation of this cyanobacterium, collected from New Britain, Papua New
      Guinea, yielded a novel cytotoxic cyclic depsipeptide, bouillonamide (1), along
      with previously reported molecules, ulongamide A and apratoxin A. Planar
      structure of bouillonamide was established by extensive 1D and 2D NMR
      experiments, including multi-edited HSQC, TOCSY, HBMC, and ROESY experiments. In
      addition to the presence of alpha-amino acid residues, compound 1 contained two
      unique polyketide-derived moieties, namely a 2-methyl-6-methylamino-hex-5-enoic
      acid (Mmaha) residue and a unit of 3-methyl-5-hydroxy-heptanoic acid (Mhha).
      Absolute stereochemistry of the alpha-amino acid units in bouillonamide was
      determined mainly by Marfey's analysis. Compound 1 exhibited mild toxicity with
      IC50's of 6.0 uM against the neuron 2a mouse neuroblastoma cells.

PMID- 23966035
TI  - Structural characterization of new microcystins containing tryptophan and
      oxidized tryptophan residues.
AB  - Microcystins are cyclic peptides produced by cyanobacteria, which can be harmful
      to humans and animals when ingested. Eight of the (more than) 90 microcystin
      variants presently characterized, contain the amino acid tryptophan. The well
      researched oxidation products of tryptophan; kynurenine, oxindolylalanine, and N
      formylkynurenine, have been previously identified in intact polypeptides but
      microcystin congeners containing oxidized tryptophan moieties have not been
      reported. Liquid chromatography-tandem mass spectrometric analysis of an extract
      of Microcystis CAWBG11 led to the tentative identification of two new tryptophan
      containing microcystins (MC-WAba and MC-WL), as well as eight other microcystin
      analogs containing kynurenine, oxindolylalanine and N-formylkynurenine (Nfk).
      Investigation of one of these congeners (MC-NfkA) by nuclear magnetic resonance
      spectroscopy was used to verify the presence of Nfk in the microcystin. Liquid
      chromatography-mass spectrometry analysis of a tryptophan oxidation experiment
      demonstrated that tryptophan-containing microcystins could be converted into
      oxidized tryptophan analogs and that low levels of oxidized tryptophan congeners
      were present intracellularly in CAWBG11. MC-NfkR and MC-LNfk were detected in
      standards of MC-WR and MC-LW, indicating that care during storage of tryptophan
      containing microcystins is required. 

PMID- 23966037
TI  - Cytotoxic anthranilic acid derivatives from deep sea sediment-derived fungus
      Penicillium paneum SD-44.
AB  - Five new anthranilic acid derivatives, penipacids A-E (1-5), together with one
      known analogue (6), which was previously synthesized, were characterized from the
      ethyl acetate extract of the marine sediment-derived fungus Penicillium paneum SD
      44. Their structures were elucidated mainly by extensive NMR spectroscopic and
      mass spectrometric analysis. The cytotoxicity and antimicrobial activity of the
      isolated compounds were evaluated. Compounds 1, and 5 exhibited inhibitory
      activity against human colon cancer RKO cell line, while compound 6 displayed
      cytotoxic activity against Hela cell line. 

PMID- 23966036
TI  - An aeroplysinin-1 specific nitrile hydratase isolated from the marine sponge
      Aplysina cavernicola.
AB  - A nitrile hydratase (NHase) that specifically accepts the nitrile aeroplysinin-1
      (1) as a substrate and converts it into the dienone amide verongiaquinol (7) was
      isolated, partially purified and characterized from the Mediterranean sponge
      Aplysina cavernicola; although it is currently not known whether the enzyme is of
      sponge origin or produced by its symbiotic microorganisms. The formation of
      aeroplysinin-1 and of the corresponding dienone amide is part of the chemical
      defence system of A. cavernicola. The latter two compounds that show strong
      antibiotic activity originate from brominated isoxazoline alkaloids that are
      thought to protect the sponges from invasion of bacterial pathogens. The sponge
      was shown to contain at least two NHases as two excised protein bands from a non
      denaturating Blue Native gel showed nitrile hydratase activity, which was not
      observed for control samples. The enzymes were shown to be manganese dependent,
      although cobalt and nickel ions were also able to recover the activity of the
      nitrile hydratases. The temperature and pH optimum of the studied enzymes were
      found at 41  degrees C and pH 7.8. The enzymes showed high substrate specificity
      towards the physiological substrate aeroplysinin-1 (1) since none of the
      substrate analogues that were prepared either by partial or by total synthesis
      were converted in an in vitro assay. Moreover de-novo sequencing by mass
      spectrometry was employed to obtain information about the primary structure of
      the studied NHases, which did not reveal any homology to known NHases. 

PMID- 23966038
TI  - Double strand breaks and cell-cycle arrest induced by the cyanobacterial toxin
      cylindrospermopsin in HepG2 cells.
AB  - The newly emerging cyanobacterial cytotoxin cylindrospermopsin (CYN) is
      increasingly found in surface freshwaters, worldwide. It poses a potential threat
      to humans after chronic exposure as it was shown to be genotoxic in a range of
      test systems and is potentially carcinogenic. However, the mechanisms of CYN
      toxicity and genotoxicity are not well understood. In the present study CYN
      induced formation of DNA double strand breaks (DSBs), after prolonged exposure
      (72 h), in human hepatoma cells, HepG2. CYN (0.1-0.5 ug/mL, 24-96 h) induced
      morphological changes and reduced cell viability in a dose and time dependent
      manner. No significant increase in lactate dehydrogenase (LDH) leakage could be
      observed after CYN exposure, indicating that the reduction in cell number was due
      to decreased cell proliferation and not due to cytotoxicity. This was confirmed
      by imunocytochemical analysis of the cell-proliferation marker Ki67. Analysis of
      the cell-cycle using flow-cytometry showed that CYN has an impact on the cell
      cycle, indicating G0/G1 arrest after 24 h and S-phase arrest after longer
      exposure (72 and 96 h). Our results provide new evidence that CYN is a direct
      acting genotoxin, causing DSBs, and these facts need to be considered in the
      human health risk assessment. 

PMID- 23966039
TI  - BMAA inhibits nitrogen fixation in the cyanobacterium Nostoc sp. PCC 7120.
AB  - Cyanobacteria produce a range of secondary metabolites, one being the neurotoxic
      non-protein amino acid beta-N-methylamino-L-alanine (BMAA), proposed to be a
      causative agent of human neurodegeneration. As for most cyanotoxins, the function
      of BMAA in cyanobacteria is unknown. Here, we examined the effects of BMAA on the
      physiology of the filamentous nitrogen-fixing cyanobacterium Nostoc sp. PCC 7120.
      Our data show that exogenously applied BMAA rapidly inhibits nitrogenase activity
      (acetylene reduction assay), even at micromolar concentrations, and that the
      inhibition was considerably more severe than that induced by combined nitrogen
      sources and most other amino acids. BMAA also caused growth arrest and massive
      cellular glycogen accumulation, as observed by electron microscopy. With nitrogen
      fixation being a process highly sensitive to oxygen species we propose that the
      BMAA effects found here may be related to the production of reactive oxygen
      species, as reported for other organisms. 

PMID- 23966040
TI  - Anti-apoptotic activity in deep pelvic endometriosis.
AB  - Since endometriosis is a proliferative disease we evaluated the presence of anti
      apoptotic factor (Bcl-2) and pro-apoptotic factor (Bax) in deep pelvic
      endometriosis. A Cross-sectional observational study was performed at Santa Casa
      de Misericordia de Sao Paulo, Sao Paulo, Brazil. Forty women aged 26 to 46 years
      with deep endometriosis were selected. They had not been clinically treated for
      at least 3 months prior to surgery and then underwent surgical laparoscopy to
      treat the disease. During the surgery, tissue was collected from the uterosacral
      ligaments and the rectosigmoid; an endometrial biopsy was also performed as a
      control. All interventions were performed by the same surgeon. The specimens were
      sent for pathological and immunohistochemical analyses; endometriosis was
      confirmed in all patients. After the immunohistochemical reaction a semi
      quantitative evaluation of the staining intensity (relative optical density-ROD)
      was conducted, applying the digital densitometric analysis system. In the
      uterosacral ligaments 97.5% of the specimens were positive for Bcl2 whereas in
      the rectosigmoid 100% were positive. In the endometrium we observed that 87.5%
      were positive for Bcl2. BAX expression was null in the rectosigmoid and in the
      endometrium. In the uterosacral ligaments 2.5% of the specimens expressed BAX.
      The relative optical density of Bcl2 was higher in the rectosigmoid and in the
      uterosacral ligament when compared to the endometrium, 0.141+/-0.002; 0.129+/
      0.001, respectively (p<0.01). We concluded that the anti-apoptotic factor Bcl-2
      was expressed in all studied specimens, but in a higher staining intensity in the
      rectosigmoid and in the uterossacral ligaments in comparison to the endometrium.
      The pro-apoptotic factor Bax had virtually no expression in the studied tissues.

PMID- 23966041
TI  - Bringing order to polymers.

PMID- 23966048
TI  - Spintronics: Solar spin devices see the light.

PMID- 23966042
TI  - Multiscale materials modelling at the mesoscale.

PMID- 23966049
TI  - Colossal permittivity materials: Doping for superior dielectrics.

PMID- 23966050
TI  - Cell migration: Towards the void.

PMID- 23966051
TI  - Material witness: Yet more layers.

PMID- 23966052
TI  - Xanthoceraside inhibits pro-inflammatory cytokine expression in Abeta25-35/IFN
      gamma-stimulated microglia through the TLR2 receptor, MyD88, nuclear factor
      kappaB, and mitogen-activated protein kinase signaling pathways.
AB  - An accumulating body of evidence suggests that Alzheimer's disease (AD) is
      associated with microglia-mediated neuroinflammation and pro-inflammatory
      cytokine expression. Therefore, the suppression of neuroinflammation and pro
      inflammatory cytokine might theoretically slow down the progression of AD.
      Xanthoceraside, a novel triterpenoid saponin extracted from the husks of
      Xanthoceras sorbifolia Bunge, has potent antiinflammatory and neuroprotective
      effects. However, the molecular mechanism underlying its anti-inflammatory action
      remains unclear. In the present study, we attempted to determine the effects of
      xanthoceraside on the production of pro-inflammatory mediators in amyloid beta25
      35 (Abeta25-35)/interferon-gamma (IFN-gamma)-stimulated microglia. Our results
      indicated that xanthoceraside (0.01 and 0.1 MUM) significantly inhibited the
      release of nitric oxide (NO) and pro-inflammatory cytokines interleukin-1beta and
      tumor necrosis factor-alpha in a concentration-dependent manner. Reverse
      transcriptase-polymerase chain reaction and western blotting analyses showed that
      xanthoceraside decreased the Abeta25-35/IFN-gamma-induced production of
      cyclooxygenase-2 and inducible NO synthase. These effects were accompanied by
      inhibited activities of nuclear factor-kappaB and mitogen-activated protein
      kinase through Toll-like receptor 2 in a myeloid differentiation protein 88
      dependent manner. Our results provide support for the therapeutic potential of
      xanthoceraside in AD.

PMID- 23966053
TI  - Heart rate as a possible therapeutic guide for the prevention of cardiovascular
      disease.
AB  - Epidemiologic evidence indicates that an elevated heart rate (HR) is an
      independent predictor of all-cause and cardiovascular (CV) mortality. Ivabradine,
      a pure HR-lowering agent, reduces CV events in patients with coronary artery
      disease (CAD) and chronic heart failure, and indicate that an HR greater than 70
      b.p.m. is hazardous. These findings demonstrate not only that an elevated HR is
      an epiphenomenon of CV risk status but also that an elevated HR itself should be
      a therapeutic target. In addition, recent epidemiologic evidence demonstrates
      that the in-treatment HR or HR change predicts subsequent all-cause and CV
      mortality, independent of the HR-lowering strategy. Characteristics of the in
      treatment HR or HR change are also important as possible therapeutic guides for
      risk management. However, there have been concerns regarding deleterious effects
      on CV event prevention owing to beta-blocker-derived pharmacologic HR reduction.
      The potential role of HR and its modulation should be considered in future
      guidance documents. 

PMID- 23966054
TI  - Endothelium-derived hyperpolarizing factor and hypertension.

PMID- 23966055
TI  - RhoGEF-mediated vasoconstriction in hypertension.

PMID- 23966056
TI  - Onset threshold of the plasma levels of soluble fms-like tyrosine kinase
      1/placental growth factor ratio for predicting the imminent onset of preeclampsia
      within 4 weeks after blood sampling at 19-31 weeks of gestation.
AB  - Our aim was to evaluate the onset threshold of plasma levels of the soluble fms
      like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio for
      predicting the imminent onset of preeclampsia (PE) within 4 weeks after blood
      sampling. We prospectively measured the plasma levels of sFlt-1 and PlGF by an
      automated electrochemiluminescence immunoassay at 19-25 weeks of gestation in
      1199 women and at 26-31 weeks of gestation in 798 women. The onset threshold of
      the sFlt-1/PlGF ratio was determined as the 2.5th percentile of the 95th
      confidence interval (CI) of a regression line between the onset gestational weeks
      of PE and the standard deviation score of log10(sFlt-1/PlGF), using 25 samples
      taken within 1 week after the onset of PE. The imminent onset of PE was
      identified in 2 (0.2%) women recruited at 19-25 weeks and in 6 (0.8%) women
      recruited at 26-31 weeks. The onset threshold of plasma levels of the sFlt-1/PlGF
      ratio at 19-25 weeks showed a sensitivity (SE) of 1.00, a specificity (SP) of
      1.00, a positive likelihood ratio (LR+) of infinity and a positive predictive
      value (PPV) of 1.00; the onset threshold of plasma levels of the sFlt-1/PlGF
      ratio at 26-31 weeks showed a SE of 0.83, a SP of 0.994, a LR+ of 132 (95% CI: 51
      339) and a PPV of 0.50. In conclusion, the onset threshold of plasma levels of
      the sFlt-1/PlGF ratio was shown to be a highly sensitive and a highly specific
      screening method for detecting the imminent onset of PE within 4 weeks after
      blood sampling at 19-31 weeks. 

PMID- 23966057
TI  - Effect of antihypertensive medication adherence on hospitalization for
      cardiovascular disease and mortality in hypertensive patients.
AB  - Antihypertensive medication treatment is one effective management strategy to
      prevent cardiovascular disease (CVD) and mortality. However, little research has
      been conducted on the rates of antihypertensive medication adherence and the
      effect of antihypertensive medication adherence on health outcomes in South
      Korea. We searched the Korean National Health Insurance Claims Database for
      records from 2003 to 2007. Patients in this study were 18 years of age or older
      and they were diagnosed with hypertension and newly prescribed antihypertensive
      medication in 2003. Adherence to antihypertensive medication was estimated as the
      medication possession ratio (MPR). Multivariate Cox regression was used to
      evaluate the association between medication adherence and adverse health outcomes
      after adjusting for patient demographics and clinical characteristics. Our study
      population consisted of 40,408 patients with a mean age of 51 years. Among the
      patients, 50.3% were men, 4.0% had Medicaid health insurance, 17.8% had diabetes,
      20.9% had dyslipidemia and 42.4% were adherent (MPR >= 80%). Nonadherent patients
      (MPR<80%) were younger and more likely to have Medicaid health insurance; they
      had lower rates of diabetes and dyslipidemia compared with adherent patients. In
      the Cox multivariate analysis, nonadherence increased the risk of all adverse
      health outcomes, including all-cause mortality and hospitalization for CVD
      (hazard ratio: 1.57, confidence interval: 1.40-1.76). In conclusion, our study
      indicates that medication adherence is important for reducing hospitalization due
      to CVD and mortality.

PMID- 23966058
TI  - Effects of weight on blood pressure at rest and during exercise.
AB  - Body weight (BW) and blood pressure (BP) have a close relationship, which has
      been accounted for by hormonal changes. No previous study has evaluated the
      effect of wearing an external weight vest on BP to determine whether there is a
      simple mechanism between BW and BP. Seventeen healthy volunteers underwent weight
      reduction (WR) through caloric restriction. Before and after WR, BW, body fat
      percentage and BP at rest and during exercise were measured. Before and after WR,
      exercise testing was performed twice with the random allocation of a weight vest
      (10 kg) during one of the tests. Linear regression was used to detect independent
      associations between BP and the weight vest, BW and body fat percentage. BW
      decreased from 89.4 +/- 15.4 kg to 79.1 +/- 14.0 kg following WR (P<0.001). WR
      led to significant decreases in BP at rest (from 130.0/85.9 mm Hg to 112.5/77.8
      mm Hg, P<0.001 for systolic and diastolic BPs) and during exercise. The weight
      vest significantly increased BP at rest (to 136.1/90.7 mm Hg before and
      125.8/84.6 mm Hg after WR) and during exercise. Linear regression analysis
      identified an independent association between the weight vest and BP (P=0.006 for
      systolic BP and P=0.009 for diastolic BP at rest). This study demonstrates that
      wearing an external weight vest has immediate effects on BP at rest and during
      exercise independent of BW or body fat. More research is needed to understand the
      physiological mechanisms between weight and BP.

PMID- 23966059
TI  - Hypoadiponectinemia and aldosterone excess are associated with lack of blood
      pressure control in subjects with resistant hypertension.
AB  - Obesity, arterial stiffness and high aldosterone levels can interact to cause
      resistant hypertension (RHTN). Lower adiponectin (APN) levels may be
      significantly associated with hypertension. However, the importance of
      hypoadiponectinemia as a complicating factor in the lack of blood pressure (BP)
      control in individuals with RHTN has not been demonstrated. Ninety-six RHTN
      patients were classified into uncontrolled (UCRHTN, n = 44) and controlled
      (CRHTN, n = 52) subgroups. Their APN and aldosterone levels, office and
      ambulatory BP (ABPM) measurements, endothelium-dependent brachial artery
      responses (flow-mediated dilation (FMD)), left ventricular mass index (LVMI) and
      pulse wave velocity (PWV) were evaluated. The UCRHTN subgroup had increased
      aldosterone levels, as well as higher LVMI and PWV. In addition, lower APN levels
      and impaired FMD response were found in this subgroup. The brachial and ABPM
      pulse pressures were inversely associated with the APN levels (r = -0.45, P =
      0.002; r = -0.33, P = 0.03, respectively), as were the aldosterone levels and the
      PWV (r = -0.38, P = 0.01; r = -0.36, P = 0.02, respectively) in UCRHTN patients.
      The PWV was only significantly influenced by the APN level in the UCRHTN subgroup
      in the multivariate regression analysis. None of the correlations mentioned above
      were observed in the CRHTN subgroup. Hypoadiponectinemia and high aldosterone
      levels may therefore be implicated in resistance to antihypertensive therapy
      related to arterial stiffness.

PMID- 23966060
TI  - Understanding and mimicking the dual optimality of the fly ear.
AB  - The fly Ormia ochracea has the remarkable ability, given an eardrum separation of
      only 520 MUm, to pinpoint the 5 kHz chirp of its cricket host. Previous research
      showed that the two eardrums are mechanically coupled, which amplifies the
      directional cues. We have now performed a mechanics and optimization analysis
      which reveals that the right coupling strength is key: it results in
      simultaneously optimized directional sensitivity and directional cue linearity at
      5 kHz. We next demonstrated that this dual optimality is replicable in a
      synthetic device and can be tailored for a desired frequency. Finally, we
      demonstrated a miniature sensor endowed with this dual-optimality at 8 kHz with
      unparalleled sound localization. This work provides a quantitative and
      mechanistic explanation for the fly's sound-localization ability from a new
      perspective, and it provides a framework for the development of fly-ear inspired
      sensors to overcoming a previously-insurmountable size constraint in engineered
      sound-localization systems.

PMID- 23966061
TI  - Designing cooperativity into the designed protein Top7.
AB  - The topology of the designed protein Top7 is not found in natural proteins. Top7
      shows signatures of non-cooperative folding in both experimental studies and
      computer simulations. In particular, molecular dynamics of coarse-grained
      structure-based models of Top7 show a well-populated C-terminal folding
      intermediate. Since most similarly sized globular proteins are cooperative
      folders, the non-natural topology of Top7 has been suggested as a reason for its
      non-cooperative folding. Here, we computationally examine the folding of Top7
      with the intent of making it cooperative. We find that its folding cooperativity
      can be increased in two ways: (a) Optimization of packing interactions in the N
      terminal half of the protein enables further folding of the C-terminal
      intermediate. (b) Reduction in the packing density of the C-terminal region
      destabilizes the intermediate. In practice, these strategies are implemented in
      our Top7 model through modifications to the contact-map. These modifications do
      not alter the topology of Top7 but result in cooperative folding. Amino-acid
      mutations that mimic these modifications also lead to a significant increase in
      folding cooperativity. Finally, we devise a method to randomize the sizes of
      amino-acids within the same topology, and confirm that the structure of Top7
      makes its folding sensitive to packing interactions. In contrast, the ribosomal
      protein S6, which has secondary structure similar to Top7, has folding which is
      much less sensitive to packing perturbations. Thus, it should be possible to make
      a sequence fold cooperatively to the structure of Top7, but to do so its side
      chain packing needs to be carefully designed.

PMID- 23966062
TI  - Establishment of an SEBM/EBM China Outreach Office in Shanghai.

PMID- 23966063
TI  - Carbon-coated Li3 N nanofibers for advanced hydrogen storage.
AB  - 3D porous carbon-coated Li3 N nanofibers are successfully fabricated via the
      electrospinning technique. The as-prepared nanofibers exhibit a highly improved
      hydrogen-sorption performance in terms of both thermodynamics and kinetics. More
      interestingly, a stable regeneration can be achieved due to the unique structure
      of the nanofibers, over 10 cycles of H2 sorption at a temperature as low as 250 
      degrees C. 

PMID- 23966064
TI  - A primigravida with very-long-chain acyl-CoA dehydrogenase deficiency.

PMID- 23966065
TI  - Serum IL-17A in newly diagnosed treatment-naive patients with ulcerative colitis
      reflects clinical disease severity and predicts the course of disease.
AB  - BACKGROUND: The clinical course of ulcerative colitis (UC) is unpredictable. The
      need for reliable biomarkers to reflect disease severity and predict disease
      course is therefore large. We investigated whether cytokines in mucosal tissue
      and serum reflect clinical disease severity at the onset of UC and predict the
      future disease course. METHODS: We prospectively monitored 102 patients from the
      onset of UC during 3 years, and they were followed up yearly for clinical and
      biochemical disease severity. Rectal biopsies were obtained from healthy controls
      and patients with UC. Serum and stool samples were obtained from patients with
      UC. Total mRNA from biopsies was analyzed with real-time PCR. Cytokine levels in
      serum were determined using Luminex or ELISA. RESULTS: Mucosal mRNA expression of
      IL-17A was 99.8 times higher while IFN-gamma and IL-13 expression was increased
      12.4 and 6.7 times, respectively, in patients relative to controls. Serum IL-17A
      correlated with clinical disease severity at the onset. Also, contrary to a
      number of other parameters, serum IL-17A at the onset predicted the clinical and
      biochemical course of the disease, as reflected by the Mayo score, number *
      severity of flares, and fecal calprotectin levels, respectively, during 3 years
      after the onset of the disease. None of these associations were found with
      mucosal cytokines at the onset. CONCLUSIONS: Serum IL-17A levels of treatment
      naive patients with UC reflect clinical disease severity at the onset of the
      disease and also predicted the disease course over the following 3 years. Thus,
      serum IL-17A may be valuable in the clinical management of patients with UC at
      the onset of the disease.

PMID- 23966066
TI  - Malignant melanoma arising in the setting of epidermolysis bullosa simplex: an
      important distinction from epidermolysis bullosa nevus.
AB  - IMPORTANCE: Patients with epidermolysis bullosa (EB) do not carry a significantly
      increased risk of melanoma but are prone to developing large, markedly atypical
      melanocytic nevi (EB nevi), which may mimic melanoma clinically and
      histologically. Many authors now favor a conservative approach in managing
      atypical pigmented lesions in patients with EB. OBSERVATIONS: We present the case
      of a 30-year-old woman with severe EB simplex who sought care for a large red and
      black ulcerated plaque. The clinical differential diagnosis included EB nevus and
      melanoma. An incisional punch biopsy specimen revealed an atypical melanocytic
      proliferation with focal florid pagetoid spread and involving elongated rete
      ridges, consistent with invasive acral lentiginous melanoma. The subsequent
      amputation was confirmatory. Micrometastasis was detected in 1 of 5 sentinel
      lymph nodes. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first
      reported case of melanoma arising in EB simplex-affected skin. It highlights the
      difficulty in differentiating melanoma from an EB nevus. Despite the increasing
      awareness of EB nevi, a high index of suspicion for melanoma should be
      maintained, and early biopsy is recommended when evaluating large pigmented
      lesions in patients with EB.

PMID- 23966067
TI  - Varenicline and cytisine diminish the dysphoric-like state associated with
      spontaneous nicotine withdrawal in rats.
AB  - Tobacco addiction is characterized by a negative mood state upon smoking
      cessation and relapse after periods of abstinence. Clinical studies indicate that
      negative mood states lead to craving and relapse. The partial
      alpha4/alpha6/beta2* nicotinic acetylcholine receptor (nAChR) agonists
      varenicline and cytisine are widely used as smoking cessation treatments.
      Varenicline has been approved in the United States for smoking cessation and
      cytisine is used in Eastern European countries. Despite the widespread use of
      these compounds, very little is known about their effects on mood states. These
      studies investigated the effects of varenicline, cytisine, and the cytisine
      derivative 3-(pyridin-3'-yl)-cytisine (3-pyr-Cyt) on brain reward function in
      nicotine-naive and nicotine-withdrawing rats. The cytisine-derivative 3-pyr-Cyt
      is a very weak alpha4beta2* nAChR partial agonist and like cytisine and
      varenicline has antidepressant-like effects in animal models. The intracranial
      self-stimulation (ICSS) procedure was used to investigate the effects of these
      compounds on brain reward function. Elevations in ICSS thresholds reflect a
      dysphoric state and a lowering of thresholds is indicative of a potentiation of
      brain reward function. It was shown that acute administration of nicotine and
      varenicline lowered ICSS thresholds. Acute administration of cytisine or 3-pyr
      Cyt did not affect ICSS thresholds. Discontinuation of chronic, 14 days, nicotine
      administration led to elevations in ICSS thresholds that lasted for about 2 days.
      Varenicline and cytisine, but not 3-pyr-Cyt, diminished the nicotine withdrawal
      induced elevations in ICSS thresholds. In conclusion, these studies indicate that
      varenicline and cytisine diminish the dysphoric-like state associated with
      nicotine withdrawal and may thereby prevent relapse to smoking in humans. 

PMID- 23966068
TI  - Binge alcohol drinking by mice requires intact group 1 metabotropic glutamate
      receptor signaling within the central nucleus of the amygdala.
AB  - Despite the fact that binge alcohol drinking (intake resulting in blood alcohol
      concentrations (BACs) ?80 mg% within a 2-h period) is the most prevalent form of
      alcohol-use disorders (AUD), a large knowledge gap exists regarding how this form
      of AUD influences neural circuits mediating alcohol reinforcement. The present
      study employed integrative approaches to examine the functional relevance of
      binge drinking-induced changes in glutamate receptors, their associated
      scaffolding proteins and certain signaling molecules within the central nucleus
      of the amygdala (CeA). A 30-day history of binge alcohol drinking (for example, 4
      5 g kg(-1) per 2 h(-1)) elevated CeA levels of mGluR1, GluN2B, Homer2a/b and
      phospholipase C (PLC) beta3, without significantly altering protein expression
      within the adjacent basolateral amygdala. An intra-CeA infusion of mGluR1, mGluR5
      and PLC inhibitors all dose-dependently reduced binge intake, without influencing
      sucrose drinking. The effects of co-infusing mGluR1 and PLC inhibitors were
      additive, whereas those of coinhibiting mGluR5 and PLC were not, indicating that
      the efficacy of mGluR1 blockade to lower binge intake involves a pathway
      independent of PLC activation. The efficacy of mGluR1, mGluR5 and PLC inhibitors
      to reduce binge intake depended upon intact Homer2 expression as revealed through
      neuropharmacological studies of Homer2 null mutant mice. Collectively, these data
      indicate binge alcohol-induced increases in Group1 mGluR signaling within the CeA
      as a neuroadaptation maintaining excessive alcohol intake, which may contribute
      to the propensity to binge drink. 

PMID- 23966070
TI  - Study of the Warner-Bratzler shear force, sensory analysis and sarcomere length
      as indicators of the tenderness of sun-dried beef.
AB  - Sun-dried beef is a frequently consumed and valued product in Brazil, however,
      there have been no scientific studies on its texture. To assess the tenderness of
      sun-dried beef, an instrumental analysis (Warner-Bratzler Shear Force; WBSF), a
      sensory analysis (Quantitative Descriptive Analysis; QDA) and the sarcomere
      length (SL) were used as indicators. Significant differences were observed among
      the sun-dried beef samples. Sample 3 (composed of sun-dried meat purchased at
      three fairs from Region 3 in the city of Joao Pessoa-PB) was considered the most
      tender by the assessors, with a score of 6.7, and its WBSF analysis revealed a
      maximum value of 2.70 kgf. Additionally, this sample exhibited the highest SL
      value (1.89 um). Samples 1 and 2 (composed of sun-dried meat purchased at three
      fairs from Regions 1 and 2, respectively, in the city of Joao Pessoa) exhibited
      very similar tenderness values (WBSF and QDA) but differed in their SL values,
      which suggested that sample 2 was the least tender. In conclusion, these results
      demonstrate that the studied parameters are complementary and can be used as
      tenderness indicators for sun-dried beef. However, although the difference was
      beyond the detection limit of the assessors and the texturometer, the SL analysis
      appears to have been the most effective. 

PMID- 23966071
TI  - Electronic structure and mesoscopic simulations of nonylphenol ethoxylate
      surfactants. a combined DFT and DPD study.
AB  - The aim of this work was to gain insight into the effect of ethylene oxide (EO)
      chains on the properties of a series of nonylphenol ethoxylate (NPE) surfactants.
      We performed a theoretical study of NPE surfactants by means of density
      functional theory (DFT) and dissipative particle dynamics (DPD). Both
      approximations were used separately to obtain different properties. Four NPEs
      were selected for this purpose (EO = 4, 7, 11 and 15 length chains). DFT methods
      provided some electronic properties that are related to the EO units. One of them
      is the solvation Gibbs energy, which exhibited a linear trend with EO chain
      length. DPD calculations allow us to observe the dynamic behavior in water of the
      NPE surfactants. We propose a coarse-grained model which properly simulates the
      mesophases of each surfactant. This model can be used in other NPEs applications.

PMID- 23966072
TI  - Probing early misfolding events in prion protein mutants by NMR spectroscopy.
AB  - The post-translational conversion of the ubiquitously expressed cellular form of
      the prion protein, PrPC, into its misfolded and pathogenic isoform, known as
      prion or PrPSc, plays a key role in prion diseases. These maladies are denoted
      transmissible spongiform encephalopathies (TSEs) and affect both humans and
      animals. A prerequisite for understanding TSEs is unraveling the molecular
      mechanism leading to the conversion process whereby most alpha-helical motifs are
      replaced by beta-sheet secondary structures. Importantly, most point mutations
      linked to inherited prion diseases are clustered in the C-terminal domain region
      of PrPC and cause spontaneous conversion to PrPSc. Structural studies with PrP
      variants promise new clues regarding the proposed conversion mechanism and may
      help identify "hot spots" in PrPC involved in the pathogenic conversion. These
      investigations may also shed light on the early structural rearrangements
      occurring in some PrPC epitopes thought to be involved in modulating prion
      susceptibility. Here we present a detailed overview of our solution-state NMR
      studies on human prion protein carrying different pathological point mutations
      and the implications that such findings may have for the future of prion
      research. 

PMID- 23966069
TI  - Mass spectrometry imaging, an emerging technology in neuropsychopharmacology.
AB  - Mass spectrometry imaging is a powerful tool for directly determining the
      distribution of proteins, peptides, lipids, neurotransmitters, metabolites and
      drugs in neural tissue sections in situ. Molecule-specific imaging can be
      achieved using various ionization techniques that are suited to different
      applications but which all yield data with high mass accuracies and spatial
      resolutions. The ability to simultaneously obtain images showing the
      distributions of chemical species ranging from metal ions to macromolecules makes
      it possible to explore the chemical organization of a sample and to correlate the
      results obtained with specific anatomical features. The imaging of biomolecules
      has provided new insights into multiple neurological diseases, including
      Parkinson's and Alzheimer's disease. Mass spectrometry imaging can also be used
      in conjunction with other imaging techniques in order to identify correlations
      between changes in the distribution of important chemical species and other
      changes in the properties of the tissue. Here we review the applications of mass
      spectrometry imaging in neuroscience research and discuss its potential. The
      results presented demonstrate that mass spectrometry imaging is a useful
      experimental method with diverse applications in neuroscience. 

PMID- 23966073
TI  - Chemical composition and cytotoxicity evaluation of essential oil from leaves of
      Casearia sylvestris, its main compound alpha-zingiberene and derivatives.
AB  - Casearia sylvestris (Salicaceae), popularly known as "guacatonga", is a plant
      widely used in folk medicine to treat various diseases, including cancer. The
      present work deals with the chemical composition as well as the cytotoxic
      evaluation of its essential oil, its main constituent and derivatives. Thus, the
      crude essential oil from leaves of C. sylvestris was obtained using a Clevenger
      type apparatus and analyzed by GC/MS. This analysis afforded the identification
      of 23 substances, 13 of which corresponded to 98.73% of the total oil
      composition, with sesquiterpene a-zingiberene accounting for 50% of the oil. The
      essential oil was evaluated for cytotoxic activity against several tumor cell
      lines, giving IC50 values ranging from 12 to 153 mg/mL. Pure a-zingiberene,
      isolated from essential oil, was also evaluated against the tumor cell lines
      showing activity for HeLa, U-87, Siha and HL60 cell lines, but with IC50 values
      higher than those determined for the crude essential oil. Aiming to evaluate the
      effect of the double bonds of a-zingiberene on the cytotoxic activity, partially
      hydrogenated a-zingiberene (PHZ) and fully hydrogenated a-zingiberene (THZ)
      derivatives were obtained. For the partially hydrogenated derivative only
      cytotoxic activity to the B16F10-Nex2 cell line (IC50 65 mg/mL) was detected,
      while totally hydrogenated derivative showed cytotoxic activity for almost all
      cell lines, with B16F10-Nex2 and MCF-7 as exceptions and with IC50 values ranging
      from 34 to 65 mg/mL. These results indicate that cytotoxic activity is related
      with the state of oxidation of compound.

PMID- 23966074
TI  - Efficient synthesis of boron-containing alpha-acyloxyamide analogs via microwave
      irradiation.
AB  - In this report, a Passerini three-component reaction utilizing boron-containing
      carboxylic acids or aldehydes is discussed. The reaction was carried out in water
      and facilitated by the use of microwave irradiation. This methodology allowed for
      the efficient formation of a broad range of boron-containing alpha-acyloxyamides
      under mild conditions within a short time. Two series of boron-containing alpha
      acyloxyamides were synthesized and subsequently screened for cytotoxicity using
      the MTT cell viability assay. Two potential lead compounds were found to have
      potent activity against the HepG2 cancer cell line, demonstrating the potential
      of this methodology for use in the development of novel pharmaceuticals. 

PMID- 23966075
TI  - The click reaction as an efficient tool for the construction of macrocyclic
      structures.
AB  - The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC, known as the click
      reaction) is an established tool used for the construction of complex molecular
      architectures. Given its efficiency it has been widely applied for
      bioconjugation, polymer and dendrimer synthesis. More recently, this reaction has
      been utilized for the efficient formation of rigid or shape-persistent,
      preorganized macrocyclic species. This strategy also allows the installment of
      useful functionalities, in the form of polar and function-rich 1,2,3-triazole
      moieties, directly embedded in the macrocyclic structures. This review analyzes
      the state of the art in this context, and provides some elements of perspective
      for future applications. 

PMID- 23966076
TI  - Alkyne-azide "click" chemistry in designing nanocarriers for applications in
      biology.
AB  - The alkyne-azide cycloaddition, popularly known as the "click" reaction, has been
      extensively exploited in molecule/macromolecule build-up, and has offered
      tremendous potential in the design of nanomaterials for applications in a diverse
      range of disciplines, including biology. Some advantageous characteristics of
      this coupling include high efficiency, and adaptability to the environment in
      which the desired covalent linking of the alkyne and azide terminated moieties
      needs to be carried out. The efficient delivery of active pharmaceutical agents
      to specific organelles, employing nanocarriers developed through the use of
      "click" chemistry, constitutes a continuing topical area of research. In this
      review, we highlight important contributions click chemistry has made in the
      design of macromolecule-based nanomaterials for therapeutic intervention in
      mitochondria and lipid droplets. 

PMID- 23966077
TI  - Melaleuca alternifolia concentrate inhibits in vitro entry of influenza virus
      into host cells.
AB  - Influenza virus causes high morbidity among the infected population annually and
      occasionally the spread of pandemics. Melaleuca alternifolia Concentrate (MAC) is
      an essential oil derived from a native Australian tea tree. Our aim was to
      investigate whether MAC has any in vitro inhibitory effect on influenza virus
      infection and what mechanism does the MAC use to fight the virus infection. In
      this study, the antiviral activity of MAC was examined by its inhibition of
      cytopathic effects. In silico prediction was performed to evaluate the
      interaction between MAC and the viral haemagglutinin. We found that when the
      influenza virus was incubated with 0.010% MAC for one hour, no cytopathic effect
      on MDCK cells was found after the virus infection and no immunofluorescence
      signal was detected in the host cells. Electron microscopy showed that the virus
      treated with MAC retained its structural integrity. By computational simulations,
      we found that terpinen-4-ol, which is the major bioactive component of MAC, could
      combine with the membrane fusion site of haemagglutinin. Thus, we proved that MAC
      could prevent influenza virus from entering the host cells by disturbing the
      normal viral membrane fusion procedure. 

PMID- 23966078
TI  - Accidental interaction between PDZ domains and diclofenac revealed by NMR
      assisted virtual screening.
AB  - In silico approaches have become indispensable for drug discovery as well as drug
      repositioning and adverse effect prediction. We have developed the eF-seek
      program to predict protein-ligand interactions based on the surface structure of
      proteins using a clique search algorithm. We have also developed a special
      protein structure prediction pipeline and accumulated predicted 3D models in the
      Structural Atlas of the Human Genome (SAHG) database. Using this database, genome
      wide prediction of non-peptide ligands for proteins in the human genome was
      performed, and a subset of predicted interactions including 14 PDZ domains was
      then confirmed by NMR titration. Surprisingly, diclofenac, a non-steroidal anti
      inflammatory drug, was found to be a non-peptide PDZ domain ligand, which bound
      to 5 of 15 tested PDZ domains. The critical residues for the PDZ-diclofenac
      interaction were also determined. Pharmacological implications of the accidental
      PDZ-diclofenac interaction are further discussed. 

PMID- 23966079
TI  - Evaluation of the effect of different growth media and temperature on the
      suitability of biofilm formation by Enterobacter cloacae strains isolated from
      food samples in South Africa.
AB  - This study evaluated the effects of growth medium, temperature, and incubation
      time on biofilm formation by Enterobacter cloacae strains. The ability to adhere
      to a surface was demonstrated using a microtiter plate adherence assay whereas
      the role of cell surface properties in biofilm formation was assessed using the
      coaggregation and autoaggregation assays. The architecture of the biofilms was
      examined under scanning electron microscope (SEM). All the strains adhered to the
      well of the microtiter plate when incubated for 48 h, irrespective of the growth
      medium and incubation temperature. It was also noted that 90% and 73% of strains
      prepared from nutrient broth and cultured in brain heart infusion (BHI) broth and
      tryptic soy broth (TSB), respectively, were able to form biofilms, in contrast to
      73% and 60% strains from nutrient agar and cultured in BHI and TSB respectively
      grown under similar conditions. However, no statistically significant difference
      was observed when the two methods were compared. The coaggregation index ranged
      from 12% to 74%, with the best coaggregate activity observed when partnered with
      Streptococcus pyogenes (54%-74%). The study indicates the suitability of BHI and
      TSB medium for the cultivation of E. cloacae biofilms, however, temperature and
      incubation time significantly affect biofilm formation by these bacteria. 

PMID- 23966080
TI  - Characterization and bioactivity of polysaccharides obtained from pine cones of
      Pinus koraiensis by graded ethanol precipitation.
AB  - Pinus koraiensis polysaccharides (PKP) were extracted by hot water from P.
      koraiensis pine cones. Five polysaccharide fractions named PKP-A, PKP-B, PKP-C,
      PKP-D and PKP-E were successfully separated at final ethanol concentrations of
      30%, 50%, 60%, 70% and 80%, respectively. HPLC, FT-IR, GC-MS and automatic amino
      acid analysis were applied to investigate their chemical characteristics.
      Monosaccharide component analysis indicated that the five fractions were all
      composed of D-ribose, L-rhamnose, L-arabinose, D-xylose, D-mannose, D-glucose and
      D-galactose, but their molar ratios were quite different. HPLC results revealed
      that the polysaccharides precipitated by higher concentrations of ethanol
      solution had lower molecular masses. Moreover, the antioxidant activities of the
      five fractions were studied on the basis of hydroxyl radical and ABTS radical
      scavenging tests. The five graded polysaccharide fractions exhibited good
      inhibitory power, and MTT tests in vitro showed the IC50 of PKP-A and PKP-E were
      1,072.5 and 2,070.0 MUg . mL-1, respectively. These results demonstrated that the
      PKP could be a potential source of natural antioxidants or dietary supplements.

PMID- 23966081
TI  - Neuroprotective, anti-amyloidogenic and neurotrophic effects of apigenin in an
      Alzheimer's disease mouse model.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      extracellular senile plaques and intracellular neurofibrillary tangles in the
      brain. Amyloid-beta peptides (Abeta) are considered to play a critical role in
      the onset and progression of AD. Apigenin (4',5,7-trihydroxyflavone) is a
      pharmacologically active agent. Even though some evidence suggests that it has
      potential neuroprotective effects, no preexisting study has reported any
      therapeutic effects of apigenin in AD models. In the present study, we examined
      the effects of apigenin on cognitive function in APP/PS1 double transgenic AD
      mice and explored its mechanism(s) of action. Three-month oral treatment with
      apigenin rescued learning deficits and relieved memory retention in APP/PS1 mice.
      Apigenin also showed effects affecting APP processing and preventing Abeta burden
      due to the down-regulation of BACE1 and beta-CTF levels, the relief of Abeta
      deposition, and the decrease of insoluble Abeta levels. Moreover, apigenin
      exhibited superoxide anion scavenging effects and improved antioxidative enzyme
      activity of superoxide dismutase and glutathione peroxidase. In addition,
      apigenin restored neurotrophic ERK/CREB/BDNF pathway in the cerebral cortex. In
      conclusion, apigenin may ameliorate AD-associated learning and memory impairment
      through relieving Abeta burden, suppressing amyloidogenic process, inhibiting
      oxidative stress, and restoring ERK/CREB/BDNF pathway. Therefore, apigenin
      appears to represent an alternative medication for the prevention and/or therapy
      of AD. 

PMID- 23966082
TI  - Anti-lung cancer activity through enhancement of immunomodulation and induction
      of cell apoptosis of total triterpenes extracted from Ganoderma luncidum (Leyss.
      ex Fr.) Karst.
AB  - Ganoderma luncidum (Leyss. ex Fr.) Karst. (GLK) has been used traditionally for
      the prevention and treatment of cancers or tumors for a long time in Traditional
      Chinese Medicine. The triterpenes as main effective components of GLK have been
      found to be beneficial for the efficacy. The purpose of this study was to examine
      the anti-lung cancer activity of triterpenes of GLK in vitro and in vivo and to
      explore their anti-lung cancer effects and potential mechanisms. A549 cells and
      Lewis tumor-bearing mice were used to evaluate the inhibition effects of
      triterpenes on cell proliferation and tumor growth. The IC50 of triterpenes of
      GLK on A549 cells was 24.63 MUg/mL. Triterpenes of GLK could significantly
      inhibit tumor growth in mice (30, 60 and 120 mg/kg). The immune organs indexes
      including spleen and thymus were increased remarkedly by the treatment with
      triterpenes. Moreover, they were able to stimulate the immune response by
      increasing the expressions of IL-6 and TNF-alpha. Flow cytometric analysis
      revealed that cell arrest caused by triterpenes treatment (7.5, 15 and 30 MUg/mL)
      was in the G2/M phase in A549 cells. Triterpenes induced apoptosis by decreasing
      the expression of the antiapoptotic protein Bcl-2 and pro-caspase 9 and
      increasing the levels of cleaved-caspase 9. Our findings suggested that the
      triterpenes of GLK have anti-lung cancer activity in vitro and in vivo via
      enhancement of immunomodulation and induction of cell apoptosis. The study
      provides insights into the mechanism of GLK in the prevention and treatment of
      lung cancer. 

PMID- 23966083
TI  - Enantio- and periselective nitroalkene Diels-Alder reactions catalyzed by helical
      chiral hydrogen bond donor catalysts.
AB  - Helical-chiral double hydrogen bond donor catalysts promote the nitroalkene Diels
      Alder reaction in an enantio- and periselective manner. This represents the first
      asymmetric catalytic nitroalkene Diels-Alder reaction via LUMO-lowering
      catalysis. To gain an insight into this new process, the substrate scope of our
      catalyst was investigated by exploiting readily available 5-substituted
      pentamethylcyclopentadienes. The catalyst was found to tolerate dienes with
      different steric demands as well as dienes substituted with heteroatoms. The
      synthetic utility of 5-substituted pentamethylcyclopentadienes is rather limited,
      and thus we have developed a three-step route to 1,4,5,5-tetrasubstituted
      cyclopentadienes from commercially available ketones. 

PMID- 23966084
TI  - Combination of small molecule microarray and confocal microscopy techniques for
      live cell staining fluorescent dye discovery.
AB  - Discovering new fluorochromes is significantly advanced by high-throughput
      screening (HTS) methods. In the present study a combination of small molecule
      microarray (SMM) prescreening and confocal laser scanning microscopy (CLSM) was
      developed in order to discover novel cell staining fluorescent dyes. Compounds
      with high native fluorescence were selected from a 14,585-member library and
      further tested on living cells under the microscope. Eleven compartment-specific,
      cell-permeable (or plasma membrane-targeted) fluorochromes were identified. Their
      cytotoxicity was tested and found that between 1-10 micromolar range, they were
      non-toxic even during long-term incubations. 

PMID- 23966085
TI  - Antianxiety-like effects of Chimpi (dried citrus peels) in the elevated open
      platform test.
AB  - Dried citrus peels (Chimpi) is one of the most common natural medicines with qi
      (energy flow) rectifying and shi (dampness) drying actions, which originates from
      Citrus unshiu, and/or C. reticulata according to the definition of the
      pharmacopoeiae of Japan and China. In this study, the pharmacological effects of
      their extracts and major chemical constituents hesperidin and its aglycone
      hesperetin on anxiety were examined with an anxiety model of elevated open
      platform test using ICR male mice (6-week-old) and total duration of freezing was
      decreased in fluoxetine-treated mice, which is a simple and highly sensitive to
      the effects of serotonergic anxiolytics. Moreover, yokukansankachimpihange (YKH),
      a combination of yokukansan with Chimpi and Hange (Pinellia) was also examined
      because Chimpi is considered to play a crucial part in this formula against
      anxious symptoms in dementia patients. The results showed that Chimpi and YKH
      possess a significant anxiolytic-like effect similar to that of fluoxetine,
      suggesting that they might be similar to fluoxetine in their pharmacological
      actions through the serotonergic neurotransmission pathway. Moreover, it also
      suggested that the major chemical constituent, hesperidin could be an active
      principle attributed to the antianxiety-like effects with a direct and indirect
      role via its aglycone hesperetin. 

PMID- 23966086
TI  - Volatile aroma compounds in various brewed green teas.
AB  - This study identifies and semi-quantifies aroma volatiles in brewed green tea
      samples. The objectives of this study were to identify using a gas chromatograph
      mass spectrometer (GC-MS) paired with a headspace solid-phase micro-extraction
      (HS-SPME) the common volatile compounds that may be responsible for aroma/flavor
      of the brewed liquor of a range of green tea samples from various countries as
      consumed and to determine if green teas from the same region have similarities in
      volatile composition when green tea samples are prepared for consumption. Twenty
      four green tea samples from eight different countries were brewed as recommended
      for consumer brewing. The aroma volatiles were extracted by HS-SPME, separated on
      a gas chromatograph and identified using a mass spectrometer. Thirty-eight
      compounds were identified and the concentrations were semi-quantified. The
      concentrations were lower than those reported by other researchers, probably
      because this research examined headspace volatiles from brewed tea rather than
      solvent extraction of leaves. No relationship to country of origin was found,
      which indicates that other factors have a greater influence than country of
      origin on aroma. 

PMID- 23966087
TI  - Total synthesis, cytotoxic effects of damnacanthal, nordamnacanthal and related
      anthraquinone analogues.
AB  - Naturally occurring anthraquinones, damnacanthal (1) and nordamnacanthal (2) were
      synthesized with modified reaction steps and investigated for their cytotoxicity
      against the MCF-7 and K-562 cancer cell lines, respectively. Intermediate
      analogues 2-bromomethyl-1,3-dimethoxyanthraquinone (5, IC50 = 5.70 +/- 0.21 and
      8.50 +/- 1.18 mg/mL), 2-hydroxymethyl-1,3-dimethoxyanthraquinone (6, IC50 = 12.10
      +/- 0.14 and 14.00 +/- 2.13), 2-formyl-1,3-dimethoxyantharquinone (7, IC50 =
      13.10 +/- 1.02 and 14.80 +/- 0.74), 1,3-dimethoxy-2-methylanthraquinone (4, IC50
      = 9.40 +/- 3.51 and 28.40 +/- 2.33), and 1,3-dihydroxy-2-methylanthraquinone (3,
      IC50 = 25.60 +/- 0.42 and 28.40 +/- 0.79) also exhibited moderate cytotoxicity
      against MCF-7 and K-562 cancer cell lines, respectively. Other structurally
      related compounds like 1,3-dihydroxyanthraquinone (13a, IC50 = 19.70 +/- 0.35 and
      14.50 +/- 1.28), 1,3-dimethoxyanthraquinone (13b, IC50 = 6.50 +/- 0.66 and 5.90
      +/- 0.95) were also showed good cytotoxicity. The target compound damnacanthal
      (1) was found to be the most cytotoxic against the MCF-7 and K-562 cancer cell
      lines, with IC50 values of 3.80 +/- 0.57 and 5.50 +/- 1.26, respectively. The
      structures of all compounds were elucidated with the help of detailed
      spectroscopic techniques. 

PMID- 23966088
TI  - Modeling the interaction of dodecylphosphocholine micelles with the anticoccidial
      peptide PW2 guided by NMR data.
AB  - Antimicrobial peptides are highly dynamic entities that acquire structure upon
      binding to a membrane interface. To better understand the structure and the
      mechanism for the molecular recognition of dodecylphosphocholine (DPC) micelles
      by the anticoccidial peptide PW2, we performed molecular dynamics (MD)
      simulations guided by NMR experimental data, focusing on strategies to explore
      the transient nature of micelles, which rearrange on a millisecond to second
      timescale. We simulated the association of PW2 with a pre-built DPC micelle and
      with free-DPC molecules that spontaneously forms micelles in the presence of the
      peptide along the simulation. The simulation with spontaneous micelle formation
      provided the adequate environment which replicated the experimental data. The
      unrestrained MD simulations reproduced the NMR structure for the entire 100 ns MD
      simulation time. Hidden discrete conformational states could be described.
      Coulomb interactions are important for initial approximation and hydrogen bonds
      for anchoring the aromatic region at the interface, being essential for the
      stabilization of the interaction. Arg9 is strongly attached with phosphate. We
      observed a helix elongation process stabilized by the intermolecular peptide
      micelle association. Full association that mimics the experimental data only
      happens after complete micelle re-association. Fast micelle dynamics without
      dissociation of surfactants leads to only superficial binding. 

PMID- 23966089
TI  - Evaluation of silica-H2SO4 as an efficient heterogeneous catalyst for the
      synthesis of chalcones.
AB  - We report an efficient silica-H2SO4 mediated synthesis of a variety of chalcones
      that afforded the targeted compounds in very good yield compared to base
      catalyzed solvent free conditions as well as acid or base catalyzed refluxing
      conditions. 

PMID- 23966090
TI  - Magnetocaloric effect and slow magnetic relaxation in two only azido bridged
      ferromagnetic tetranuclear metal clusters.
AB  - Two M(II) tetranuclear complexes bridged only by azido, Mn4(N3)(7.3)Cl(0.7)L4 (1)
      and Co4(N3)8L4 (2) in which the four M(II) ions are precisely coplanar bridged
      only by six azido anions, were obtained by using 4,5-diazafluoren-9-one (L) as a
      corner ligand. Magnetic studies indicate that ferromagnetic coupling was
      conducted by the azido anions between M(II) ions. At low temperature, 1 exhibits
      a large magnetocaloric effect and 2 shows field-induced multiple magnetic
      relaxations.

PMID- 23966091
TI  - Quantitative computed tomography of diffuse lung disease.

PMID- 23966092
TI  - Establishing normal reference values in quantitative computed tomography of
      emphysema.
AB  - Quantitative computed tomography (QCT) can provide reliable and valid measures of
      lung structure and volumes. Similar to lung function measured by spirometry, lung
      measures obtained by QCT vary by demographic and anthropomorphic factors
      including sex, race/ethnicity, and height in asymptomatic nonsmokers. Hence,
      accounting for these factors is necessary to define abnormal from normal QCT
      values. Prediction equations for QCT may be derived from a sample of asymptomatic
      individuals to estimate reference values. This review article describes the
      methodology of reference equation development using, as an example, quantitative
      densitometry to detect pulmonary emphysema. The process described is
      generalizable to other QCT measures, including lung volumes, airway dimensions,
      and gas-trapping. Pulmonary emphysema is defined morphologically by airspace
      enlargement with alveolar wall destruction and has been shown to correlate with
      low lung attenuation estimated by QCT. Deriving reference values for a normal
      quantity of low lung attenuation requires 3 steps. First, criteria that define
      normal must be established. Second, variables for inclusion must be selected on
      the basis of an understanding of subject-specific, scanner-specific, and protocol
      specific factors that influence lung attenuation. Finally, a reference sample of
      normal individuals must be selected that is representative of the population in
      which QCT will be used to detect pulmonary emphysema. Sources of bias and
      confounding inherent to reference values are also discussed. Reference equation
      development is a multistep process that can define normal values for QCT measures
      such as lung attenuation. Normative reference values will increase the utility of
      QCT in both research and clinical practice. 

PMID- 23966093
TI  - Computed tomography as a biomarker in clinical trials imaging.
AB  - There has been increasing interest in developing novel pulmonary biomarkers to
      assist in drug and device development in the setting of patients with chronic
      obstructive pulmonary disease and diffuse parenchymal lung disease. In this
      review we discuss which computed tomography (CT)-based biomarkers are currently
      being implemented and the challenges inherent in their development, validation,
      and implementation in multicenter trials. CT scans provide valuable information
      about lung structure and function but face challenges with respect to
      standardization across multiple sites and time points; in addition, the concern
      around radiation has to be considered. There is relatively little information
      about how any of these biomarkers relate to other clinical outcomes such as
      progression of disease, severity of disease, clinical subtypes, or response to
      therapy. Additional information is also needed about the variability in these
      measurements. In the future, CT biomarkers may be useful in predicting disease
      progression, in indicating disease instability, and in predicting response to
      current and novel therapies, many of which are now under development. 

PMID- 23966094
TI  - Quantitative computed tomography imaging of interstitial lung diseases.
AB  - PURPOSE: High-resolution chest computed tomography (HRCT) is essential in the
      characterization of interstitial lung disease. The HRCT features of some diseases
      can be diagnostic. Longitudinal monitoring with HRCT can assess progression of
      interstitial lung disease; however, subtle changes in the volume and character of
      abnormalities can be difficult to assess. Accuracy of diagnosis can be dependent
      on expertise and experience of the radiologist, pathologist, or clinician.
      Quantitative analysis of thoracic HRCT has the potential to determine the extent
      of disease reproducibly, classify the types of abnormalities, and automate the
      diagnostic process. MATERIALS AND METHODS: Novel software that utilizes histogram
      signatures to characterize pulmonary parenchyma was used to analyze chest HRCT
      data, including retrospective processing of clinical CT scans and research data
      from the Lung Tissue Research Consortium. Additional information including
      physiological, pathologic, and semiquantitative radiologist assessment was
      available to allow comparison of quantitative results, with visual estimates of
      the disease, physiological parameters, and measures of disease outcome. RESULTS:
      Quantitative analysis results were provided in regional volumetric quantities for
      statistical analysis and a graphical representation. These results suggest that
      quantitative HRCT analysis can serve as a biomarker with physiological,
      pathologic, and prognostic significance. CONCLUSIONS: It is likely that
      quantitative analysis of HRCT can be used in clinical practice as a means to aid
      in identifying a probable diagnosis, stratifying prognosis in early disease, and
      consistently determining progression of the disease or response to therapy.
      Further optimization of quantitative techniques and longitudinal analysis of well
      characterized subjects would be helpful in validating these methods.

PMID- 23966095
TI  - Cardiac computed tomography in the emergency department.

PMID- 23966097
TI  - Partnering for Vaccine Emerging Markets--Berlin, June 10-11, 2013: balancing
      vaccine quality, capacity, and cost-of-goods in emerging markets.
AB  - Phacilitates 1st Partnering event for Vaccine Emerging Markets brought together
      approximately 100 attendees from developed and developing world vaccine
      manufacturers, leading non-profit organizations and industry suppliers. The goal
      was to discuss the vaccine needs in the developing world and how these needs can
      be met by leveraging collaboration and partnership models, by improving access to
      existing, new and next generation vaccines, by using novel technologies to drive
      competitive advantage and economics of vaccine manufacturing and by investing in
      localized capacity, including capacity for pandemic vaccines. The present article
      summarizes insights out of 30 oral contributions on how quality and capacity
      requirements can be balanced with cost by using novel manufacturing technologies
      and operating models. 

PMID- 23966098
TI  - Modern Vaccines/Adjuvants Formulation--Session 2 (Plenary II): May 15-17, 2013-
      Lausanne, Switzerland.
AB  - On the 15-17th May 2013, the Fourth International Conference on Modern
      Vaccines/Adjuvants Formulation was organized in Lausanne, Switzerland, and
      gathered stakeholders from academics and from the industry to discuss several
      challenges, advances and promises in the field of vaccine adjuvants. Plenary
      session 2 of the meeting was composed of four different presentations covering:
      (1) the recent set-up of an adjuvant technology transfer and training platform in
      Switzerland, (2) the proposition to revisit existing paradigms of modern
      vaccinology, (3) the properties of polyethyleneimine as potential new vaccine
      adjuvant, and (4) the progresses in the design of HIV vaccine candidates able to
      induce broadly neutralizing antibodies. 

PMID- 23966100
TI  - Lineage-specific molecular probing reveals novel diversity and ecological
      partitioning of haplosporidians.
AB  - Haplosporidians are rhizarian parasites of mostly marine invertebrates. They
      include the causative agents of diseases of commercially important molluscs,
      including MSX disease in oysters. Despite their importance for food security,
      their diversity and distributions are poorly known. We used a combination of
      group-specific PCR primers to probe environmental DNA samples from planktonic and
      benthic environments in Europe, South Africa and Panama. This revealed several
      highly distinct novel clades, novel lineages within known clades and seasonal
      (spring vs autumn) and habitat-related (brackish vs littoral) variation in
      assemblage composition. High frequencies of haplosporidian lineages in the water
      column provide the first evidence for life cycles involving planktonic hosts,
      host-free stages or both. The general absence of haplosporidian lineages from all
      large online sequence data sets emphasises the importance of lineage-specific
      approaches for studying these highly divergent and diverse lineages. Combined
      with host-based field surveys, environmental sampling for pathogens will enhance
      future detection of known and novel pathogens and the assessment of disease risk.

PMID- 23966099
TI  - Genome sequencing of a single cell of the widely distributed marine subsurface
      Dehalococcoidia, phylum Chloroflexi.
AB  - Bacteria of the class Dehalococcoidia (DEH), phylum Chloroflexi, are widely
      distributed in the marine subsurface, yet metabolic properties of the many
      uncultivated lineages are completely unknown. This study therefore analysed
      genomic content from a single DEH cell designated 'DEH-J10' obtained from the
      sediments of Aarhus Bay, Denmark. Real-time PCR showed the DEH-J10 phylotype was
      abundant in upper sediments but was absent below 160 cm below sea floor. A 1.44
      Mbp assembly was obtained and was estimated to represent up to 60.8% of the full
      genome. The predicted genome is much larger than genomes of cultivated DEH and
      appears to confer metabolic versatility. Numerous genes encoding enzymes of core
      and auxiliary beta-oxidation pathways were identified, suggesting that this
      organism is capable of oxidising various fatty acids and/or structurally related
      substrates. Additional substrate versatility was indicated by genes, which may
      enable the bacterium to oxidise aromatic compounds. Genes encoding enzymes of the
      reductive acetyl-CoA pathway were identified, which may also enable the fixation
      of CO2 or oxidation of organics completely to CO2. Genes encoding a putative
      dimethylsulphoxide reductase were the only evidence for a respiratory terminal
      reductase. No evidence for reductive dehalogenase genes was found. Genetic
      evidence also suggests that the organism could synthesise ATP by converting
      acetyl-CoA to acetate by substrate-level phosphorylation. Other encoded enzymes
      putatively conferring marine adaptations such as salt tolerance and organo
      sulphate sulfohydrolysis were identified. Together, these analyses provide the
      first insights into the potential metabolic traits that may enable members of the
      DEH to occupy an ecological niche in marine sediments. 

PMID- 23966101
TI  - Ancestral reproductive structure in basal kelp Aureophycus aleuticus.
AB  - Laminarialean species (so-called kelps) are the largest photosynthetic organisms
      in aquatic environments, constituting significant ecological components of
      coastal ecosystems. The largest kelps such as Macrocystis exhibit differentiation
      between stipe and blade, as well as buoyancy to maintain the distal portion at
      the water's surface for photosynthesis, while bearing reproductive structures
      only near the base on special blades (sporophylls). There is a considerable gap
      between basic kelps such as Chorda and derived kelps, and the evolution of kelp
      specialization remains unclear. Here we report novel reproductive adaptations in
      the recently discovered species Aureophycus aleuticus; unlike any known kelps, A.
      aleuticus forms zoidangia only on the expanded, disc-shaped holdfast. Molecular
      phylogeny suggests that A. aleuticus is most basal among derived kelps. Because
      Aureophycus lacks any of the elaborate anatomical structures found in other
      derived kelps, we suggest that it exhibits some of the most ancestral
      morphological features of kelps. 

PMID- 23966102
TI  - Predictors of Mortality among Tuberculosis/HIV-Coinfected Persons in Southwest
      Ethiopia: A Case-Control Study.
AB  - BACKGROUND: Tuberculosis (TB) remains the most common cause of death in people
      living with HIV/AIDS. The aim of the present study was to identify predictors of
      mortality in TB/HIV-coinfected patients. METHODS: We conducted an unmatched case
      control study among a cohort of TB/HIV-coinfected adults who were on
      antiretroviral therapy (ART). Cases comprised 69 TB/HIV-coinfected patients who
      died during this period. For each case, we selected 3 (207) TB/HIV-coinfected
      patients who were alive during the end of the follow-up period. RESULTS: Male sex
      (odds ratio [OR] = 2.04, 95% confidence interval [CI]: 1.04-4.02), being
      bedridden at enrollment (OR = 2.84, 95% CI: 1.17-6.89), and cough of more than 2
      weeks during initiation of ART (OR = 4.75 95% CI: 2.14-10.56) were the best
      predictors of mortality among TB/HIV-coinfected patients. CONCLUSION: Mortality
      among TB/HIV-coinfected patients accounted for a considerable number of deaths
      among the cohort. Patients with cough at ART initiation and with poor functional
      status should be strictly followed to reduce death.

PMID- 23966103
TI  - The role of Sep (O-phosphoserine) tRNA: Sec (selenocysteine) synthase (SEPSECS)
      in proliferation, apoptosis and hormone secretion of trophoblast cells.
AB  - OBJECTIVES: To investigate whether Sep (O-phosphoserine) tRNA: Sec
      (selenocysteine) synthase (SEPSECS), which plays an essential role in the
      synthesis of selenoprotein, affects proliferation, apoptosis and hormone
      secretion of human trophoblast cells. METHODS: Human trophoblast JEG-3 cells were
      divided into four groups: control group, SEPSECS silenced-expression group, empty
      vector group and SEPSECS over-expression group. Over-expression and silenced
      expression were achieved by transfection with plasmid DNA or RNA oligonucleotide,
      respectively. 3-[4,5-dimethylthiazol-2-yl] -2,5-diphenyltetrazolium bromide (MTT)
      and colony formation assays were performed to investigate cell proliferation,
      while apoptosis was tested by annexin V-FITC, PI double staining and caspases-3
      activation assays, enzyme-linked immunosorbent assay (ELISA) was used to
      determine the level of progesterone (PG) and human chorionic gonadotropin (hCG).
      RESULTS: SEPSECS silenced-expression clearly inhibited proliferation of JEG-3
      cells (p < 0.05), significantly induced cell apoptosis (p < 0.01) and reduced the
      production of PG and hCG (p < 0.05). On the contrary, SEPSECS over-expression
      significantly promoted both cell proliferation (p < 0.01) and secretion of PG and
      hCG (p < 0.05). CONCLUSIONS: SEPSECS significantly affects proliferation,
      apoptosis and hormone secretion of human trophoblast cells, suggesting that a
      potential relationship exists among SEPSECS, cell proliferation, apoptosis and
      hormone production of human placental trophoblast cells. Furthermore, this may
      provide a clue to uncover the relationship between selenium and human placental
      in association with an emphasis on the importance of selenium adequacy during
      pregnancy.

PMID- 23966104
TI  - The liver and the kidney: two critical organs influencing the atherothrombotic
      risk in metabolic syndrome.
AB  - The increased atherothrombotic risk in patients with metabolic syndrome (MetS)
      has been classically explained by the multiplicative effect of systemic
      concomitant pro-atherosclerotic factors. In particular, centripetal obesity,
      dyslipidaemia, glucose intolerance, hypertension (differently combined in the
      diagnosis of the disease) would be expected to act as classical cardiovascular
      risk conditions underlying accelerated atherogenesis. In order to better
      understand specific atherosclerotic pathophysiology in MetS, emerging evidence
      focused on the alterations in different organs that could serve as both
      pathophysiological targets and active players in the disease. Abnormalities in
      adipose tissue, heart and arteries have been widely investigated in a variety of
      basic research and clinical studies in MetS. In this narrative review, we focus
      on pathophysiological activities of the liver and kidney. Considering its key
      role in metabolism and production of soluble inflammatory mediators (such as C
      reactive protein [CRP]), the liver in MetS has been shown to be altered both in
      its structure and function. In particular, a relevant amount of the fat
      accumulated within this organ has been shown to be associated with different
      degrees of inflammation and potential insulin resistance. In humans, non
      alcoholic fatty liver disease (NAFLD) has been described as the hepatic
      manifestation of MetS. In an analogous manner, epidemiological evidence strongly
      suggested a "guilty" association between MetS and chronic kidney disease (CKD).
      Some biomarkers of hepatic (such as C-reactive protein, TNF-alpha or other
      cytokines) and renal diseases (such as uric acid) associated with MetS might be
      particularly useful to better manage and prevent the atherothrombotic risk. 

PMID- 23966105
TI  - Oral deferiprone for iron chelation in people with thalassaemia.
AB  - BACKGROUND: Thalassaemia major is a genetic disease characterised by a reduced
      ability to produce haemoglobin. Management of the resulting anaemia is through
      red blood cell transfusions.Repeated transfusions result in an excessive
      accumulation of iron in the body (iron overload), removal of which is achieved
      through iron chelation therapy. A commonly used iron chelator, deferiprone, has
      been found to be pharmacologically efficacious. However, important questions
      exist about the efficacy and safety of deferiprone compared to another iron
      chelator, desferrioxamine. OBJECTIVES: To summarise data from trials on the
      clinical efficacy and safety of deferiprone and to compare the clinical efficacy
      and safety of deferiprone with desferrioxamine for thalassaemia. SEARCH METHODS:
      We searched the Cochrane Cystic fibrosis and Genetic Disorders Group's
      Haemoglobinopathies trials Register and MEDLINE, EMBASE, CENTRAL (The Cochrane
      Library), LILACS and other international medical databases, plus registers of
      ongoing trials and the Transfusion Evidence Library
      (www.transfusionevidencelibrary.com). We also contacted the manufacturers of
      deferiprone and desferrioxamine.All searches were updated to 05 March 2013.
      SELECTION CRITERIA: Randomised controlled trials comparing deferiprone with
      another iron chelator; or comparing two schedules or doses of deferiprone, in
      people with transfusion-dependent thalassaemia. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed trials for risk of bias and extracted data.
      Missing data were requested from the original investigators. MAIN RESULTS: A
      total of 17 trials involving 1061 participants (range 13 to 213 participants per
      trial) were included. Of these, 16 trials compared either deferiprone alone with
      desferrioxamine alone, or a combined therapy of deferiprone and desferrioxamine
      with either deferiprone alone or desferrioxamine alone; one compared different
      schedules of deferiprone. There was little consistency between outcomes and
      limited information to fully assess the risk of bias of most of the included
      trials.Four trials reported mortality; each reported the death of one individual
      receiving deferiprone with or without desferrioxamine. One trial reported five
      further deaths in patients who withdrew from randomised treatment (deferiprone
      with or without desferrioxamine) and switched to desferrioxamine alone. Seven
      trials reported cardiac function or liver fibrosis as measures of end organ
      damage.Earlier trials measuring the cardiac iron load indirectly by magnetic
      resonance imaging (MRI) T2* signal had suggested deferiprone may reduce cardiac
      iron more quickly than desferrioxamine. However, a meta-analysis of two trials
      suggested that left ventricular ejection fraction was significantly reduced in
      patients who received desferrioxamine alone compared with combination therapy. 
      One trial, which planned five years of follow up, was stopped early due to the
      beneficial effects of combined treatment compared with deferiprone alone in terms
      of serum ferritin levels reduction.The results of this and three other trials
      suggest an advantage of combined therapy over monotherapy to reduce iron stores
      as measured by serum ferritin. There is, however, no conclusive or consistent
      evidence for the improved efficacy of combined deferiprone and desferrioxamine
      therapy over monotherapy from direct or indirect measures of liver iron. Both
      deferiprone and desferrioxamine produce a significant reduction in iron stores in
      transfusion-dependent, iron-overloaded people. There is no evidence from
      randomised controlled trials to suggest that either has a greater reduction of
      clinically significant end organ damage.Evidence of adverse events were observed
      in all treatment groups. Occurrence of any adverse event was significantly more
      likely with deferiprone than desferrioxamine in one trial, RR 2.24 (95% CI 1.19
      to 4.23). Meta-analysis of a further two trials showed a significant increased
      risk of adverse events associated with combined deferiprone and desferrioxamine
      compared with desferrioxamine alone, RR 3.04 (95% CI 1.18 to 7.83). The most
      commonly reported adverse event was joint pain, which occurred significantly more
      frequently in patients receiving deferiprone than desferrioxamine, RR 2.64 (95%
      CI 1.21 to 5.77). Other common adverse events included gastrointestinal
      disturbances as well as neutropenia or leucopenia, or both. AUTHORS' CONCLUSIONS:
      In the absence of data from randomised controlled trials, there is no evidence to
      suggest the need for a change in current treatment recommendations; namely that
      deferiprone is indicated for treating iron overload in people with thalassaemia
      major when desferrioxamine is contraindicated or inadequate. Intensified
      desferrioxamine treatment (by either subcutaneous or intravenous route) or use of
      other oral iron chelators, or both, remains the established treatment to reverse
      cardiac dysfunction due to iron overload. Indeed, the US Food and Drug
      Administration (FDA) recently only gave support for deferiprone to be used as a
      last resort for treating iron overload in thalassaemia, myelodysplasia and sickle
      cell disease. However, there is evidence that adverse events are increased in
      patients treated with deferiprone compared with desferrioxamine and in patients
      treated with combined deferiprone and desferrioxamine compared with
      desferrioxamine alone. There is an urgent need for adequately-powered, high
      quality trials comparing the overall clinical efficacy and long-term outcome of
      deferiprone with desferrioxamine.

PMID- 23966106
TI  - See-through dye-sensitized solar cells: photonic reflectors for tandem and
      building integrated photovoltaics.
AB  - See-through dye-sensitized solar cells with 1D photonic crystal Bragg reflector
      photoanodes show an increase in peak external quantum efficiency of 47% while
      still maintaining high fill factors, resulting in an almost 40% increase in power
      conversion efficiency. These photoanodes are ideally suited for tandem and
      building integrated photovoltaics. 

PMID- 23966107
TI  - Successful treatment of severe hidradenitis suppurativa with anakinra.

PMID- 23966108
TI  - Cocoa flavonoid-enriched diet modulates systemic and intestinal immunoglobulin
      synthesis in adult Lewis rats.
AB  - Previous studies have reported that a diet containing 10% cocoa, a rich source of
      flavonoids, has immunomodulatory effects on rats and, among others effects, is
      able to attenuate the immunoglobulin (Ig) synthesis in both systemic and
      intestinal compartments. The purpose of the present study was focused on
      investigating whether these effects were attributed exclusively to the flavonoid
      content or to other compounds present in cocoa. To this end, eight-week-old Lewis
      rats were fed, for two weeks, either a standard diet or three isoenergetic diets
      containing increasing proportions of cocoa flavonoids from different sources: one
      with 0.2% polyphenols from conventional defatted cocoa, and two others with 0.4%
      and 0.8% polyphenols, respectively, from non-fermented cocoa. Diet intake and
      body weight were monitored and fecal samples were obtained throughout the study
      to determine fecal pH, IgA, bacteria proportions, and IgA-coated bacteria.
      Moreover, IgG and IgM concentrations in serum samples collected during the study
      were quantified. At the end of the dietary intervention no clear changes of serum
      IgG or IgM concentrations were quantified, showing few effects of cocoa
      polyphenol diets at the systemic level. However, in the intestine, all cocoa
      polyphenol-enriched diets attenuated the age-related increase of both fecal IgA
      and IgA-coated bacteria, as well as the proportion of bacteria in feces. As these
      effects were not dependent on the dose of polyphenol present in the diets, other
      compounds and/or the precise polyphenol composition present in cocoa raw material
      used for the diets could be key factors in this effect. 

PMID- 23966109
TI  - Linseed dietary fibers reduce apparent digestibility of energy and fat and weight
      gain in growing rats.
AB  - Dietary fibers (DF) may affect energy balance, an effect often ascribed to the
      viscous nature of some water soluble DF, which affect luminal viscosity and thus
      multiple physiological processes. We have tested the hypothesis that viscous
      linseed DF reduce apparent nutrient digestibility, and limit weight gain, in a
      randomized feeding trial where 60 male, growing, Wistar rats, with an initial
      weight of ~200 g, were fed different diets (n = 10 per group): low DF control
      (C), 5% DF from cellulose (5-CEL), CEL + 5% DF from whole (5-WL) or ground
      linseed (5-GL), CEL + 5% DF from linseed DF extract (5-LDF), and CEL + 10% DF
      from linseed DF extract (10-LDF). Diets were provided ad libitum for 21 days.
      Feed intake and faecal output were measured during days 17-21. Faecal fat
      excretion increased with increasing DF content and was highest in the 10-LDF
      group. Apparent fat digestibility was highest with the C diet (94.9% +/- 0.8%)
      and lowest (74.3% +/- 0.6%) with the 10-LDF diet, and decreased in a non-linear
      manner with increasing DF (p < 0.001). Apparent fat digestibility also decreased
      with increased accessibility of DF (5-WL vs. 5-GL) and when the proportion of
      viscous DF increased (5-GL vs. 5-LDF). The 10-LDF resulted in a lower final body
      weight (258 +/- 6.2 g) compared to C (282 +/- 5.9 g), 5-CEL (281 +/- 5.9 g), and
      5-WL (285 +/- 5.9 g) (p < 0.05). The 10-LDF diet reduced body fat compared to 5
      CEL (p < 0.01). In conclusion, DF extracted from linseed reduced apparent energy
      and fat digestibility and resulted in restriction of body weight gain in growing
      rats. 

PMID- 23966110
TI  - Docosahexaenoic acid, inflammation, and bacterial dysbiosis in relation to
      periodontal disease, inflammatory bowel disease, and the metabolic syndrome.
AB  - Docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid, has
      been used to treat a range of different conditions, including periodontal disease
      (PD) and inflammatory bowel disease (IBD). That DHA helps with these oral and
      gastrointestinal diseases in which inflammation and bacterial dysbiosis play key
      roles, raises the question of whether DHA may assist in the prevention or
      treatment of other inflammatory conditions, such as the metabolic syndrome, which
      have also been linked with inflammation and alterations in normal host microbial
      populations. Here we review established and investigated associations between
      DHA, PD, and IBD. We conclude that by beneficially altering cytokine production
      and macrophage recruitment, the composition of intestinal microbiota and
      intestinal integrity, lipopolysaccharide- and adipose-induced inflammation, and
      insulin signaling, DHA may be a key tool in the prevention of metabolic syndrome.

PMID- 23966113
TI  - Lateral talar station: a clinically reproducible measure of sagittal talar
      position.
AB  - BACKGROUND: The sagittal relationship of the talus to the tibial shaft can prove
      invaluable to the orthopedist in understanding and effectively treating ankle
      pathologies such as ligamentous laxity and ankle arthritis. Any useful
      radiographic analysis tool to assess the lateral position of the talus must be
      employable reliably in the clinical setting. Previously published measurements to
      assess the lateral translational relationship of the talus relative to the tibial
      axis may not be available in the clinical setting or may be subject to
      significant inaccuracies. We have defined a sagittal talar position measurement
      (lateral talar station; LTS), which we postulated could be used reproducibly on
      clinical radiographs by the orthopedist to define the position of the talus as it
      relates to the anatomic tibial axis. In addition, we defined the normal range of
      the LTS measurement. METHODS: A retrospective cohort of patients (121 ankles, 104
      patients) who presented to our clinic with foot pain between 2005 and 2011 was
      evaluated for inclusion in the study. Exclusion criteria included patients with
      ankle trauma, instability, prior ankle surgery, or radiographic evidence of ankle
      osteoarthrosis. The final cohort consisted of 82 ankles. The LTS was measured
      digitally for each subject on weight-bearing lateral ankle radiographs by 3
      observers. The mean LTS and standard deviation was determined for the entire
      cohort. In addition, as a means of validating our methodology, we performed an
      assessment of interobserver and intraobserver reliability in terms of the LTS
      measurements. RESULTS: The LTS measurements for the entire cohort fit a Gaussian
      distribution with a mean of 1.17 mm (SD = 0.9893 mm). Interobserver intraclass
      coefficients for 2 observers (medical student and radiologist) and intraobserver
      intraclass coefficients for 1 reader (orthopaedic surgeon) indicated excellent
      reliability, being above 0.9. CONCLUSION: The LTS was a reliable measure that
      could be used on weight-bearing lateral ankle radiographs to define sagittal
      position of the talus in a clinical setting. The normal distribution for the LTS
      was described in our study population. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 23966111
TI  - Dietary fructose feeding increases adipose methylglyoxal accumulation in rats in
      association with low expression and activity of glyoxalase-2.
AB  - Methylglyoxal is a precursor to advanced glycation endproducts that may
      contribute to diabetes and its cardiovascular-related complications.
      Methylglyoxal is successively catabolized to D-lactate by glyoxalase-1 and
      glyoxalase-2. The objective of this study was to determine whether dietary
      fructose and green tea extract (GTE) differentially regulate methylglyoxal
      accumulation in liver and adipose, mediated by tissue-specific differences in the
      glyoxalase system. We fed six week old male Sprague-Dawley rats a low-fructose
      diet (10% w/w) or a high-fructose diet (60% w/w) containing no GTE or GTE at 0.5%
      or 1.0% for nine weeks. Fructose-fed rats had higher (P < 0.05) adipose
      methylglyoxal, but GTE had no effect. Plasma and hepatic methylglyoxal were
      unaffected by fructose and GTE. Fructose and GTE also had no effect on the
      expression or activity of glyoxalase-1 and glyoxalase-2 at liver or adipose.
      Regardless of diet, adipose glyoxalase-2 activity was 10.8-times lower (P < 0.05)
      than adipose glyoxalase-1 activity and 5.9-times lower than liver glyoxalase-2
      activity. Adipose glyoxalase-2 activity was also inversely related to adipose
      methylglyoxal (r = -0.61; P < 0.05). These findings suggest that fructose
      mediated adipose methylglyoxal accumulation is independent of GTE supplementation
      and that its preferential accumulation in adipose compared to liver is due to low
      constitutive expression of glyoxalase-2.

PMID- 23966114
TI  - A ten-year experience with pediatric face grafts.
AB  - The authors reviewed their 10-year experience of performing face grafts in
      children with burns. They sought to compare different methods for aesthetic
      outcome and need for reconstruction. In addition, they determined the efficacy of
      using allograft skin or Integra as temporary covers. They performed a review of
      160 pediatric patients who underwent acute facial excision and grafting for burns
      between 2000 and 2010. Of the 160 patients with a mean age of 5.8 +/- 4.8 years,
      96 were males. The mean burn size was 39.4 +/- 24.61%, of which 36.5 +/- 25.4%
      was third degree. Overall length of stay was 72.1 days, intensive care unit
      length of stay was 44.2 days, and the mortality rate was 13.75%. Ninety patients
      had their entire face burned, 42 burned half, 15 burned their foreheads, and
      seven had other combinations. The interval between injury and grafting was 13.9
      +/- 13.19 days. Sixty-three percent patients required one face graft, 23% had
      two, 8% had three, and 6% four or more. For their initial procedure, 105 patients
      underwent autografting, 28 had allografting, and 23 received Integra. The authors
      performed a two-stage procedure in 20.4% and a 1-day procedure in 79.6%. Ten
      patients had a contiguous "U-shaped" graft wrapped around the face. At least
      partial regrafting was performed in 21.1%. Allograft and Integra were used for
      massive burns (69.9 +/- 14.5%, 62.6 +/- 18.3%, respectively). Of these, 39% died,
      17% developed an Integra infection, and 43% required regrafting before
      autografting. Overall, 24.5% of patients underwent facial reconstruction during
      their first admission, and 57.1% during subsequent admissions. No difference in
      the rate of reconstructive surgery was noted between patients receiving Integra
      or autografting. Autografting face burns as an initial, one-stage procedure works
      well. The "wrap-around" autograft leads to excellent cosmetic results. When there
      is a shortage of autograft, allograft or Integra are good options but Integra
      does not reduce the need for reconstructive surgery. 

PMID- 23966115
TI  - Admission temperature and survival in patients admitted to burn centers.
AB  - It is commonly believed that hypothermia occurring during burn resuscitation is
      associated with poor outcome, but there is little direct supporting evidence. The
      authors conducted an analysis of a statewide trauma registry to determine whether
      hypothermia (T <=36.5 degrees C) was associated with mortality when controlling
      for clinical confounders. They included all patients treated at an accredited
      burn center from 2000 to 2011 where the trauma registrar recorded the primary
      injury type as a burn. They excluded records with missing data and nonphysiologic
      temperature (<26 degrees C or >42 degrees C). The primary exposure of interest
      was hypothermia. The authors constructed a hierarchical, multivariable logistic
      regression model to examine the effect of hypothermia on survival, controlling
      for potentially confounding variables. Predictors of mortality are presented as
      odds ratio (95% confidence interval). Primary burn injury was coded 17,098 times
      during the study period. Of these, 3809 were not treated at a burn center and
      1192 were excluded for missing data. Admission hypothermia was independently
      associated with mortality (1.91 [1.58-2.29]) when adjusting for age, sex, total
      second- and third-degree burn surface area (TBSA), comorbid conditions, injury
      severity score, direct transport vs referral, method of temperature measurement,
      year, and the hospital providing care. Increasing age, female sex, TBSA >40%,
      presence of multiple comorbid conditions, and increasing injury severity score
      were associated with mortality. Other variables in the model were not
      independently associated with outcome. There was a weak correlation between TBSA
      and admission temperature (r = .18). Hypothermia at hospital admission is
      independently associated with mortality in burn patients when controlling for
      clinical confounders. Future studies should address potential causes underlying
      this observation. 

PMID- 23966112
TI  - Strengths and limitations of microarray-based phenotype prediction: lessons
      learned from the IMPROVER Diagnostic Signature Challenge.
AB  - MOTIVATION: After more than a decade since microarrays were used to predict
      phenotype of biological samples, real-life applications for disease screening and
      identification of patients who would best benefit from treatment are still
      emerging. The interest of the scientific community in identifying best approaches
      to develop such prediction models was reaffirmed in a competition style
      international collaboration called IMPROVER Diagnostic Signature Challenge whose
      results we describe herein. RESULTS: Fifty-four teams used public data to develop
      prediction models in four disease areas including multiple sclerosis, lung
      cancer, psoriasis and chronic obstructive pulmonary disease, and made predictions
      on blinded new data that we generated. Teams were scored using three metrics that
      captured various aspects of the quality of predictions, and best performers were
      awarded. This article presents the challenge results and introduces to the
      community the approaches of the best overall three performers, as well as an R
      package that implements the approach of the best overall team. The analyses of
      model performance data submitted in the challenge as well as additional
      simulations that we have performed revealed that (i) the quality of predictions
      depends more on the disease endpoint than on the particular approaches used in
      the challenge; (ii) the most important modeling factor (e.g. data preprocessing,
      feature selection and classifier type) is problem dependent; and (iii) for
      optimal results datasets and methods have to be carefully matched. Biomedical
      factors such as the disease severity and confidence in diagnostic were found to
      be associated with the misclassification rates across the different teams.
      AVAILABILITY: The lung cancer dataset is available from Gene Expression Omnibus
      (accession, GSE43580). The maPredictDSC R package implementing the approach of
      the best overall team is available at www.bioconductor.org or
      http://bioinformaticsprb.med.wayne.edu/.

PMID- 23966117
TI  - A protocol of early aggressive acceleration of tube feeding increases ileus
      without perceptible benefit in severely burned patients.
AB  - Optimal nutrition is essential to the recovery of burned patients. The authors
      evaluated the efficacy of an aggressive nutrition delivery protocol. The
      following protocol was implemented: initiation of tube feeds within 4 hours,
      acceleration to goal rate within 8 hours, and tolerance of gastric residual
      volumes of 400 ml. Patients on the protocol formed the study group whereas
      patients admitted immediately before implementation served as controls for a
      study period of 7 days after admission. Outcome variables included ileus,
      prokinetic medication use, intensive care unit and overall length of stay,
      ventilator days and mortality. Variables were compared using bivariate analysis.
      The 42 study subjects and 34 controls were similar at baseline. Time to
      initiation was similar (6.8 vs 9.4 hours; P = .226), however, goal rate was
      achieved much sooner in the study group (11.2 vs 20.9 hours; P < .001). Number of
      hours spent at goal was different on days 1 and 2 (6.62 vs 2.74, P = .003 and
      17.24 vs 13.18, P = .032) with no difference thereafter. Residual volumes in the
      study group were higher from day 2 onward, and remained increased throughout the
      study period (401 vs 234 ml average; P = .449). Clinical ileus was much more
      common in the study group (8 cases vs 1, P = .037). There was no difference in
      length of stay or mortality. The protocol was successfully implemented and
      resulted in early achievement of goal tube feed rates. However, this resulted in
      tube feed intolerance as manifested by more cases of clinical ileus. 

PMID- 23966116
TI  - Differences in resuscitation in morbidly obese burn patients may contribute to
      high mortality.
AB  - The rising number of obese patients poses new challenges for burn care. These may
      include adjustments in calculations of burn size, resuscitation, ventilator wean,
      nutritional goals as well as challenges in mobilization. The authors have focused
      this observational study on resuscitation in the obese patient population in the
      first 48 hours after burn injury. Previous trauma studies suggest a prolonged
      time to reach end points of resuscitation in the obese compared to nonobese
      injured patients. The authors hypothesize that obese patients have worse outcomes
      after thermal injury and that differences in the response to resuscitation
      contribute to this disparity. The authors retrospectively analyzed data
      prospectively collected in a multicenter trial to compare resuscitation and
      outcomes in patients stratified by National Institutes of Health/World Health
      Organization body mass index (BMI) classification (BMI: normal weight, 18.5-24.9;
      overweight, 25-29.9, obese, 30-39.9; morbidly obese, >=40). Because of the
      distribution of body habitus in the obese, total burn size was recalculated for
      all patients by using the method proposed by Neaman and compared with Lund
      Browder estimates. The authors analyzed patients by BMI class for fluids
      administered and end points of resuscitation at 24 and 48 hours. Multivariate
      analysis was used to compare morbidity and mortality across BMI groups. The
      authors identified 296 adult patients with a mean TBSA of 41%. Patient and injury
      characteristics were similar across BMI categories. No significant differences
      were observed in burn size calculations by using Neaman vs Lund-Browder formulas.
      Although resuscitation volumes exceeded the predicted formula in all BMI
      categories, higher BMI was associated with less fluid administered per actual
      body weight (P = .001). Base deficit on admission was highest in the morbidly
      obese group at 24 and 48 hours. Furthermore, the morbidly obese patients did not
      correct their metabolic acidosis to the extent of their lower BMI counterparts (P
      values .04 and .03). Complications and morbidities across BMI groups were
      similar, although examination of organ failure scores indicated more severe organ
      dysfunction in the morbidly obese group. Compared with being normal weight, being
      morbidly obese was an independent risk factor for death (odds ratio = 10.1;
      confidence interval, 1.94-52.5; P = .006). Morbidly obese patients with severe
      burns tend to receive closer to predicted fluid resuscitation volumes for their
      actual weight. However, this patient group has persistent metabolic acidosis
      during the resuscitation phase and is at risk of developing more severe multiple
      organ failure. These factors may contribute to higher mortality risk in the
      morbidly obese burn patient. 

PMID- 23966118
TI  - Quantity and quality of nocturnal sleep affect morning glucose measurement in
      acutely burned children.
AB  - Hyperglycemia after severe burn injury has long been recognized, whereas sleep
      deprivation after burns is a more recent finding. The postburn metabolic effects
      of poor sleep are not clear despite reports in other populations demonstrating
      the association between sleep insufficiency and deleterious endocrine
      consequences. The aim of this study was to determine whether a relationship
      between sleep and glucose dynamics exists in acutely burned children. Two
      overnight polysomnography runs (2200 to 0600) per subject were conducted in 40
      patients with a mean (+/- SEM) age of 9.4 +/- 0.7 years, 50.1 +/- 2.9% TBSA burn,
      and 43.2 +/- 3.6% full-thickness injury. Serum glucose was drawn in the morning
      (0600) immediately after the sleep test. Insulin requirements during the 24-hour
      period preceding the 0600 glucose measurement were recorded. Generalized linear
      models were used by the authors to evaluate percent time in each stage of sleep,
      percent wake time, total sleep time, sleep efficiency, and morning serum glucose,
      accounting for insulin use. Increased time awake (P = .04, linear; P = .02,
      quadratic) and reduced time spent in stage 1 sleep (P = .03, linear) were
      associated with higher glucose levels. Sleep efficiency (P = .01, linear; P =
      .02, quadratic) and total sleep time (P = .01 linear; P = .02, quadratic) were
      inversely associated with glucose level. Morning glucose levels appear to be
      affected by the quality and quantity of overnight sleep in children who have
      sustained extensive burn injuries. Future research is needed to elucidate the
      metabolic and neuroendocrine consequences of sleep deprivation on metabolism
      after burns. 

PMID- 23966120
TI  - Examining triage patterns of inhalation injury and toxic epidermal necrolysis
      Stevens Johnson syndrome.
AB  - The American Burn Association recommends that patients with toxic epidermal
      necrolysis-Stevens Johnson syndrome (TEN-SJS) or burn inhalation injuries would
      benefit from admission or transfer to a burn center (BC). This study examines to
      what extent those criteria are observed within a regional burn network. Hospital
      discharge data from 2000 to 2010 was obtained for all hospitals within the South
      Florida regional burn network. Patients with International Classification of
      Disease-9th revision discharge diagnoses for TEN-SJS or burn inhalation injury
      and their triage destination were compared using burn triage referral criteria to
      determine whether the patients were triaged differently from American Burn
      Association recommendations. Two hundred ninety-nine TEN-SJS and 131 inhalation
      injuries were admitted to all South Florida hospitals. Only 25 (8.4%) of TEN-SJS
      and 27 (21%) of inhalation injuries were admitted to the BC. BC patients had
      greater length of stay (TEN-SJS 22 vs 10 days; inhalation 13 vs 7) and were more
      likely to be funded by charity or be self-paid (TEN-SJS 24 vs 9.5%, P = .025;
      inhalation 44 vs 14%, P < .001), but less likely to hold some form of private or
      government insurance (TEN-SJS 72 vs 88%, P = .02; inhalation 48 vs 81%, P =
      .006). TEN-SJS BC patients were more frequently discharged home for self-care (76
      vs 50%, P = .006). Non-BC patients were more often discharged to other healthcare
      facilities (28 vs 0% TEN-SJS, 20 vs 7.4% inhalation). Inappropriate triage may
      occur in more than 3 out of 4 of the TEN-SJS and inhalation injury patients
      within our burn network. Unfamiliarity with triage criteria, patient insurance
      status, and overcoding may play a role. Further studies should fully characterize
      the problem and implement education or incentives to encourage more appropriate
      triage. 

PMID- 23966121
TI  - The persistent embryonic vein in Klippel-Trenaunay syndrome.
AB  - Klippel-Trenaunay syndrome (KTS) is a congenital malformation syndrome with
      prominent vascular anomalies. A persistent embryonic vein (PEV) may be located on
      the affected leg(s) of patients with KTS. Our understanding of PEVs of the legs
      is limited and their nomenclature is confusing. The objective of this study was
      to obtain further insight in the prevalence, nomenclature and etiology of PEVs of
      the legs in KTS and to propose a standardized description of anomalous leg veins
      in KTS. We investigated 70 KTS patients for the presence of PEVs (lateral
      marginal vein, LMV) of the legs by duplex ultrasonography. We performed
      histopathological analysis of a surgically excised PEV (LMV) of a typical KTS
      patient, and we conducted an extensive literature study. Duplex ultrasonography
      showed LMVs in 12/70 (17.1%) patients. The terms used to describe PEVs in the leg
      are quite variable, while indicating only two types: lateral marginal vein (LMV)
      and persistent sciatic vein (PSV). The histology of the excised LMV showed
      remarkable similarity with that of varicose veins found in the general
      population. In conclusion, the prevalence of LMVs in our KTS cohort is 17.1%. Two
      PEVs can be found in the legs and we propose nomenclature based on anatomical
      criteria, thereby using only the terms persistent lateral marginal vein and
      persistent sciatic vein, combined with the patency of the deep venous system. We
      hypothesize that PEVs are most likely caused by a genetic defect leading to
      abnormal venous pattern formation, which is further supported by our
      histopathological findings. 

PMID- 23966119
TI  - Genetic risk factors for hypertrophic scar development.
AB  - Hypertrophic scars (HTSs) occur in 30 to 72% patients after thermal injury. Risk
      factors include skin color, female sex, young age, burn site, and burn severity.
      Recent correlations between genetic variations and clinical conditions suggest
      that single-nucleotide polymorphisms (SNPs) may be associated with HTS formation.
      The authors hypothesized that an SNP in the p27 gene (rs36228499) previously
      associated with decreased restenosis after coronary stenting would be associated
      with lower Vancouver Scar Scale (VSS) measurements and decreased itching. Patient
      and injury characteristics were collected from adults with thermal burns. VSS
      scores were calculated at 4 to 9 months after injury. Genotyping was performed
      using real-time polymerase chain reaction. Logistic regression was used to
      determine risk factors for HTS as measured by a VSS score >7. Three hundred
      subjects had a median age of 39 years (range, 18-91); 69% were male and median
      burn size was 7% TBSA (range, 0.25-80). Consistent with literature, the p27
      variant SNP had an allele frequency of 40%, but was not associated with reduced
      HTS formation or lower itch scores in any genetic model. HTS formation was
      associated with American Indian/Alaskan Native race (odds ratio [OR], 12.2; P =
      .02), facial burns (OR, 9.4; P = .04), and burn size >=20% TBSA (OR, 1.99; P =
      .03). Although the p27 SNP may protect against vascular fibroproliferation, the
      effect cannot be generalized to cutaneous scars. This study suggests that
      American Indian/Alaskan Native race, facial burns, and higher %TBSA are
      independent risk factors for HTS. The American Indian/Alaskan Native association
      suggests that there are potentially yet-to-be-identified genetic variants. 

PMID- 23966122
TI  - SVM annual meeting - June 2013: Cleveland, OH, USA.

PMID- 23966123
TI  - Structural requirements for enzymatic activities of foamy virus protease-reverse
      transcriptase.
AB  - Reverse transcriptases (RTs) are pivotal in the life cycle of retroviruses and
      convert the genomic viral RNA into double-stranded DNA. The RT polymerase domain
      is subdivided into fingers, palm, thumb, and the connection subdomain, which
      links the polymerase to the C-terminal RNase H domain. In contrast to
      orthoretroviruses, mature RT of foamy viruses harbors the protease (PR) domain at
      its N-terminus (PR-RT). Therefore and due to low homology to other RTs, it is
      difficult to define the boundaries and functions of the (sub)domains. We
      introduced N- and C-terminal deletions into simian foamy virus PR-RT to
      investigate the impact of the truncations on the catalytic activities. Both, the
      RNase H domain and the connection subdomain contribute substantially to
      polymerase integrity and stability as well as to polymerase activity and
      substrate binding. The 42 amino acids long region C-terminal of the PR is
      important for polymerase stability and activity. PR activation via binding of PR
      RT to viral RNA requires the presence of the full length PR-RT including the
      RNase H domain. In vitro, the cleavage efficiencies of FV PR for the Gag and Pol
      cleavage site are comparable, even though in virus particles only the Pol site is
      cleaved to completion suggesting that additional factors control PR activity and
      that virus maturation needs to be strictly regulated.

PMID- 23966124
TI  - Physician attitudes in Romania toward withholding and withdrawal of intensive
      care for infants with very poor prognosis.
AB  - OBJECTIVE: The purpose of this study was to examine the attitudes of Romanian
      physicians toward withholding and withdrawing intensive care for infants whose
      prognosis is very poor. METHODS: A survey tool was developed by the authors and
      completed by participants in the annual meeting of the Neonatology Association of
      Romania. RESULTS: The majority of respondents attempt resuscitation of all live
      born infants, have never stopped resuscitation at birth while the infant was
      still alive, and have never stopped respiratory support because of poor
      prognosis. Nearly all respondents were uncomfortable talking with parents about
      withholding or withdrawing intensive care, and they were also uncomfortable
      talking to the parents about the death of their infant. CONCLUSIONS: Romanian
      physicians are uniformly reluctant to withhold or withdraw intensive care for
      infants, even those with very poor prognosis. In addition, physicians are very
      uncomfortable talking with parents about limiting or stopping support and talking
      about the death of an infant. Educational programs targeting the communication of
      difficult topics with parents have the potential to decrease the discomfort
      experienced by physicians in conversing with parents about their child's poor
      prognosis or death.

PMID- 23966125
TI  - Cytokine levels in the preterm infant with neonatal intestinal injury.
AB  - OBJECTIVES: The purpose of this study is to characterize the cytokine response of
      preterm newborns with surgical necrotizing enterocolitis (NEC) or spontaneous
      intestinal perforation (SIP) before surgical treatment and to relate these
      finding to intestinal disease (NEC vs. SIP). STUDY DESIGN: The study was a 14
      month prospective, cohort study of neonates undergoing surgery or drainage for
      NEC or SIP or surgical ligation of patent ductus arteriosus (PDA). Multiplex
      cytokine detection technology was used to analyze six inflammatory markers:
      interleukin-2, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 beta (IL
      1beta), interferon-gamma, and tumor necrosis factor-alpha (TNF-alpha). RESULTS:
      Patients with NEC had much higher median preoperative levels of IL-6 (NEC: 8,381
      pg/mL; SIP: 36 pg/mL; PDA: 25 pg/mL, p < 0.001), IL-8 (NEC: 18,438 pg/mL; SIP:
      2,473 pg/mL; PDA: 1,110 pg/mL, p = 0.001), TNF-alpha (NEC: 161 pg/mL; SIP: 77
      pg/mL; PDA: 71 pg/mL, p < 0.001), and IL-1beta (NEC: 85 pg/mL; SIP: 31 pg/mL;
      PDA: 24 pg/mL, p = 0.001). Patients with NEC totalis (NEC-totalis had the highest
      levels of IL-8 and were significantly different from infants with limited NEC
      (28,141 vs. 11,429 pg/mL, p = 0.03). CONCLUSION: Surgical NEC is a profoundly
      more proinflammatory disease than SIP. The cytokine profiles of patients with SIP
      are closer to those of a nonseptic surgical neonate.

PMID- 23966126
TI  - Minor anomalies: can they predict specific major defects? A study based on 23
      major and 14 minor anomalies in over 25,000 newborns with birth defects.
AB  - BACKGROUND: Minor anomalies (mAs) are morphological features with little clinical
      relevance that have been mentioned as possible predictors of major defects (MDs).
      OBJECTIVES: To identify the preferential associations between selected MDs and
      mAs and to establish if mAs can serve as predictors for specific MDs. STUDY
      DESIGN: Information of newborns with birth defects was obtained from the ECLAMC
      (Latin American Collaborative Study of Congenital Malformations) database. The
      sample consisted of 27,247 live- and stillborn newborns with multiple
      malformations that included at least one of the selected MDs or mAs. The odds
      ratio and predictive values were calculated for significant associations, and
      concurrence rates in first degree relatives. RESULTS: A total of 33 significant
      minor-major associations were identified. Single umbilical artery (SUA) and
      preauricular tags were the most frequent mAs; the former was associated with 10
      MDs, the latter only with microtia. The highest positive predictive value was
      shown by SUA for anal atresia. Newborns with preauricular tags had significantly
      more relatives with microtia than expected. CONCLUSIONS: No new relevant
      associations between MDs and mAs were identified and few mAs seem to serve as
      predictors for specific MDs in the same newborn. However, preauricular tags can
      predict the occurrence of microtia in other family members.

PMID- 23966127
TI  - Isolated abdominal circumference < 5% or estimated fetal weight 10 to 19% as
      predictors of small for gestational age infants.
AB  - OBJECTIVES: To determine whether (1) isolated fetal abdominal circumference < 5%
      (AC5) in absence of growth restriction (estimated fetal weight < 10% [EFW10]) or
      (2) borderline fetal growth 10 to 19% (EFW10-19) predicts subsequent fetal and/or
      neonatal growth restriction. STUDY DESIGN: The authors performed a retrospective
      cohort study (January 2008 to December 2011) of women with singleton pregnancies
      between 26 and 36 weeks who had >= 1 growth ultrasound. Univariable and
      multivariable analyses were performed to determine the association between
      isolated AC5 or EFW10-19 with both subsequent sonographic diagnosis of EFW10 and
      neonatal diagnosis of small for gestational age (SGA). Test characteristics were
      calculated. RESULTS: Out of the 10,642 pregnancies, prevalence of isolated AC5,
      EFW10-19, EFW10, and SGA were as follows: AC5, 5.31%; EFW10-19, 13.30%; EFW10,
      7.95%; and SGA, 17.63%. While screening for SGA using EFW10 alone would miss
      68.34% of SGA neonates, using isolated AC5 would identify an additional 16.15% of
      SGA neonates with a 3.7% false positive rate. Using EFW10-19 would identify an
      additional 40.20% of SGA neonates with a 9.0% false positive rate. CONCLUSION:
      Fetuses with isolated AC5 or EFW10-19 are at an increased risk of growth
      restriction. Using isolated AC5 or composite EFW10-19 would identify SGA neonates
      that are missed using conventional sonographic definitions of growth restriction
      alone.

PMID- 23966128
TI  - Adults with psychosis or psychotic experiences may report adverse life events
      prior to the onset of symptoms but direction of causality cannot be inferred.

PMID- 23966129
TI  - Centralised depression care according to patient preference is effective for the
      treatment of depression symptoms following acute coronary syndrome.

PMID- 23966131
TI  - Spatial and stimulus-type tuning in the LEC, MEC, POR, PrC, CA1, and CA3 during
      spontaneous item recognition memory.
AB  - According to the "two streams" hypothesis, the lateral entorhinal (LEC) and the
      perirhinal (PrC) cortices process information related to items (a "what" stream),
      the postrhinal (POR) and the medial entorhinal cortices (MEC) process spatial
      information (a "where" stream), and both types of information are integrated in
      the hippocampus (HIP). However, within the framework of memory function, only the
      HIP is reliably shown to preferentially process spatial information, and the PrC
      items' features. In contrast, the role of the LEC and MEC in memory is virtually
      unexplored, and conflicting results emerge for the POR. Moreover, the specific
      contribution of the hippocampal subfields CA1 and CA3 to spatial and non-spatial
      memory is not thoroughly understood. To investigate which of these areas is
      specifically tuned to spatial demands or stimulus identity (odor or object), we
      assessed the pattern of activation of these areas during recognition memory by
      detecting the immediate-early gene Arc, commonly used as a marker of neuronal
      activation. We report that all MTL areas were recruited during the spatial and
      the non-spatial tasks. However, the LEC, MEC, POR, and CA1 were activated to a
      comparable level in spatial and non-spatial tasks, while the PrC was tuned to
      stimulus-type, not spatial demands, and CA3 to spatial demands but not stimulus
      type. Results are discussed within the frame of a recent model suggesting that
      the MTL could be segregated in terms of memory processes, such as recollection
      and familiarity, rather than information content.

PMID- 23966130
TI  - Insecticidal activity of pogostone against Spodoptera litura and Spodoptera
      exigua (Lepidoptera: Noctuidae).
AB  - BACKGROUND: Essential oil of Pogostemon cablin (Blanco) Benth. has been reported
      to exhibit strong insecticidal activities, but few studies have focused on the
      insecticidal activity of its main individual constituent, pogostone (PO). The
      goal of this research was to investigate the insecticidal activity of PO against
      two harmful noctuid insects, Spodoptera litura (Fabricius) and Spodoptera exigua
      (Hubner). RESULTS: In a no-choice assay, PO exhibited strong antifeedant activity
      against S. litura and S. exigua. PO showed pronounced larvicidal activities,
      including oral toxicity (LC50 986.88 mg L(-1) and 545.61 mg L(-1) respectively)
      and contact toxicity (LC50 1041.42 mg L(-1) and 519.48 mg L(-1) respectively)
      against these two noctuid insects. Additionally, PO treatment significantly
      increased the larval and pupal developmental period. Furthermore, PO showed
      moderate ovicidal activities and influenced the emergence and deformity of the
      moth. However, PO failed to exert a potent effect on adult development. These
      tested parameters proved to be dose dependent for both insect species.
      CONCLUSION: PO possesses strong insecticidal activities, especially antifeedant,
      larvicidal, growth inhibitory and pupicidal activities, against S. litura and S.
      exigua. PO may partly account for the insecticidal activity of patchouli oil and
      may be a promising candidate for the control of agricultural insects.

PMID- 23966132
TI  - Testing Leggett's inequality using Aharonov-Casher effect.
AB  - Bell's inequality is established based on local realism. The violation of Bell's
      inequality by quantum mechanics implies either locality or realism or both are
      untenable. Leggett's inequality is derived based on nonlocal realism. The
      violation of Leggett's inequality implies that quantum mechanics is neither local
      realistic nor nonlocal realistic. The incompatibility of nonlocal realism and
      quantum mechanics has been currently confirmed by photon experiments. In our
      work, we propose to test Leggett's inequality using the Aharonov-Casher effect.
      In our scheme, four entangled particles emitted from two sources manifest a two
      qubit-typed correlation that may result in the violation of the Leggett
      inequality, while satisfying the no-signaling condition for spacelike separation.
      Our scheme is tolerant to some local inaccuracies due to the topological nature
      of the Aharonov-Casher phase. The experimental implementation of our scheme can
      be possibly realized by a calcium atomic polarization interferometer experiment. 

PMID- 23966133
TI  - Combined inhaled anticholinergics and short-acting beta2-agonists for initial
      treatment of acute asthma in children.
AB  - BACKGROUND: There are several treatment options for managing acute asthma
      exacerbations (sustained worsening of symptoms that do not subside with regular
      treatment and require a change in management). Guidelines advocate the use of
      inhaled short acting beta2-agonists (SABAs) in children experiencing an asthma
      exacerbation. Anticholinergic agents, such as ipratropium bromide and atropine
      sulfate, have a slower onset of action and weaker bronchodilating effect, but may
      specifically relieve cholinergic bronchomotor tone and decrease mucosal edema and
      secretions. Therefore, the combination of inhaled anticholinergics with SABAs may
      yield enhanced and prolonged bronchodilation. OBJECTIVES: To determine whether
      the addition of inhaled anticholinergics to SABAs provides clinical improvement
      and affects the incidence of adverse effects in children with acute asthma
      exacerbations. SEARCH METHODS: We searched MEDLINE (1966 to April 2000), EMBASE
      (1980 to April 2000), CINAHL (1982 to April 2000) and reference lists of studies
      of previous versions of this review. We also contacted drug manufacturers and
      trialists. For the 2012 review update, we undertook an 'all years' search of the
      Cochrane Airways Group's register on the 18 April 2012. SELECTION CRITERIA:
      Randomized parallel trials comparing the combination of inhaled anticholinergics
      and SABAs with SABAs alone in children (aged 18 months to 18 years) with an acute
      asthma exacerbation. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial quality and extracted data. We used the GRADE rating
      system to assess the quality of evidence for our primary outcome (hospital
      admission). MAIN RESULTS: Twenty trials met the review eligibility criteria,
      generated 24 study comparisons and comprised 2697 randomised children aged one to
      18 years, presenting predominantly with moderate or severe exacerbations. Most
      studies involved both preschool-aged children and school-aged children; three
      studies also included a small proportion of infants less than 18 months of age.
      Nine trials (45%) were at a low risk of bias. Most trials used a fixed-dose
      protocol of three doses of 250 mcg or two doses of 500 mcg of nebulized
      ipratropium bromide in combination with a SABA over 30 to 90 minutes while three
      trials used a single dose and two used a flexible-dose protocol according to the
      need for SABA.The addition of an anticholinergic to a SABA significantly reduced
      the risk of hospital admission (risk ratio (RR) 0.73; 95% confidence interval
      (CI) 0.63 to 0.85; 15 studies, 2497 children, high-quality evidence). In the
      group receiving only SABAs, 23 out of 100 children with acute asthma were
      admitted to hospital compared with 17 (95% CI 15 to 20) out of 100 children
      treated with SABAs plus anticholinergics. This represents an overall number
      needed to treat for an additional beneficial outcome (NNTB) of 16 (95% CI 12 to
      29).Trends towards a greater effect with increased treatment intensity and with
      increased asthma severity were observed, but did not reach statistical
      significance. There was no effect modification due to concomitant use of oral
      corticosteroids and the effect of age could not be explored. However, exclusion
      of the one trial that included infants (< 18 months) and contributed data to the
      main outcome, did not affect the results. Statistically significant group
      differences favoring anticholinergic use were observed for lung function,
      clinical score at 120 minutes, oxygen saturation at 60 minutes, and the need for
      repeat use of bronchodilators prior to discharge from the emergency department.
      No significant group difference was seen in relapse rates.Fewer children treated
      with anticholinergics plus SABA reported nausea and tremor compared with SABA
      alone; no significant group difference was observed for vomiting. AUTHORS'
      CONCLUSIONS: Children with an asthma exacerbation experience a lower risk of
      admission to hospital if they are treated with the combination of inhaled SABAs
      plus anticholinergic versus SABA alone. They also experience a greater
      improvement in lung function and less risk of nausea and tremor. Within this
      group, the findings suggested, but did not prove, the possibility of an effect
      modification, where intensity of anticholinergic treatment and asthma severity,
      could be associated with greater benefit.Further research is required to identify
      the characteristics of children that may benefit from anticholinergic use (e.g.
      age and asthma severity including mild exacerbation and impending respiratory
      failure) and the treatment modalities (dose, intensity, and duration) associated
      with most benefit from anticholinergic use better.

PMID- 23966134
TI  - Supramolecular helices: chirality transfer from conjugated molecules to
      structures.
AB  - Different scales of chirality endow a material with many excellent properties and
      potential applications. In this review, using pi-conjugated molecules as
      functional building blocks, recent progress on supramolecular helices inspired by
      biological helicity is summarized. First, induced chirality on conjugated
      polymers and small molecules is introduced. Molecular chirality can be amplified
      to nanostructures, superstructures, and even macroscopic structures by a self
      assembly process. Then, the principles for tuning the helicity of supramolecular
      chirality, as well as formation of helical heterojunctions, are summarized.
      Finally, the potential applications of chiral structures in chiral sensing and
      organic electronic devices are critically reviewed. Due to recent progress in
      chiral structures, an interdisciplinary area called "chiral electronics" is
      expected to gain wide popularity in the near future. 

PMID- 23966135
TI  - The psychological effects of prenatal diagnostic procedures: maternal anxiety
      before and after invasive and noninvasive procedures.
AB  - OBJECTIVES: (1) To examine the change in anxiety before and after prenatal
      diagnostic procedures in women undergoing invasive (amniocentesis) and
      noninvasive (ultrasound) procedures; and (2) to examine predictors of anxiety
      before the diagnostic procedure. METHODS: A short-term follow-up study was
      conducted on a sample of pregnant women in the second trimester. Questionnaires
      were administered to women scheduled for amniocentesis (n = 37) and
      ultrasonography (n = 37) before and immediately after the procedure. The
      following questionnaires were administered: the State-Trait Anxiety Inventory,
      the Affect Intensity Measure, the COPE inventory, and the Optimism-Pessimism
      Scale. RESULTS: Prior to the administration of the prenatal diagnostic procedure,
      measured anxiety levels were the same in both groups of women (p > 0.05). An
      interaction effect of a two-way ANOVA revealed that anxiety decreased after the
      procedure in the ultrasound but not the amniocentesis group (F(1, 72) = 5.01, p =
      0.028). Although coping styles and affect intensity were found to be related to
      anxiety (p < 0.05), they were not significant predictors of anxiety before the
      diagnostic procedure when controlling for trait anxiety and procedure type.
      CONCLUSION: Anxiety levels associated with noninvasive but not after invasive,
      prenatal diagnostics tests decrease immediately following the procedure.

PMID- 23966136
TI  - A microfluidic synchronizer for fission yeast cells.
AB  - Among all the cell cycle synchronization technologies, the baby machine may be
      considered as the most artifact-free method. A baby machine incubates "mother
      cells" under normal conditions and collects their "babies", producing cell
      cultures that are similar not only in cell cycle phase but also in age. Unlike
      many other synchronization methods, no cell-cycle-blocking agent or metabolic
      stress is introduced in this method. Several macroscale and microfluidic baby
      machines have been developed for producing synchronized cell colonies. However,
      for rod-shaped cells like fission yeast (Schizosaccharomyces pombe), it is still
      a challenge to immobilize only the mother cells in a microfluidic device. Here we
      presented a new baby machine suitable for fission yeast. The device is fixed one
      end of the cell and releases the free-end daughter cell every time the cell
      finishes cytokinesis. A variety of structures for cell immobilization were
      attempted to find the optimal design. For the convenience of collection and
      further assay, we integrated into our baby machine chip a cell screener, which
      exploited the deformation of polymer material to switch between opening and
      closing states. Synchronous populations of fission yeast cells were produced with
      this device, its working detail was analyzed and performance was evaluated. The
      device provides a new on-chip tool for cell biology studies. 

PMID- 23966137
TI  - Malignant melanoma and epidermolysis bullosa simplex.

PMID- 23966138
TI  - Cross-cultural adaptation and analysis of the psychometric properties of the
      Balance Evaluation Systems Test and MiniBESTest in the elderly and individuals
      with Parkinson's disease: application of the Rasch model.
AB  - BACKGROUND: Older adults and individuals with neurological problems such as
      Parkinson's disease (PD) exhibit balance deficits that might impair their
      mobility and independence. The assessment of balance must be useful in
      identifying the presence of instability and orient interventions. OBJECTIVE: To
      translate and perform a cross-cultural adaptation of the Balance Evaluation
      Systems Test (BESTest) and MiniBESTest to Brazilian Portuguese and analyze its
      psychometric properties. METHOD: The tests were translated and adapted to
      Portuguese according to a standard method and then subjected to a test-retest
      reliability assessment (10 older adults; 10 individuals with PD). The
      psychometric properties were assessed by the Rasch model (35 older adults; 35
      individuals with PD). RESULTS: The reliability coefficient of the tests relative
      to the items and subjects varied from 0.91 and 0.98, which is indicative of the
      stability and reproducibility of the measures. In the BESTest, the person (4.19)
      and item (5.36) separation index established six balance ability levels and seven
      levels of difficulty, respectively. In the MiniBESTest, the person (3.16) and
      item (6.41) separation index established four balance ability levels and nine
      levels of difficulty, respectively. Two items in the BESTest did not fit with the
      model expectations, but the construct validity was not compromised. No item in
      the MiniBESTest was erratic. CONCLUSIONS: The results corroborate the diagnostic
      and screening functions of the BESTest and MiniBESTest, respectively, and
      indicate that the Brazilian versions exhibit adequate reliability, construct
      validity, response stability, and capacity to distinguish among various balance
      ability levels in older adults and individuals with PD.

PMID- 23966139
TI  - Prediction equations for maximal respiratory pressures of Brazilian adolescents.
AB  - BACKGROUND: The literature emphasizes the need for studies to provide reference
      values and equations able to predict respiratory muscle strength of Brazilian
      subjects at different ages and from different regions of Brazil. OBJECTIVES: To
      develop prediction equations for maximal respiratory pressures (MRP) of Brazilian
      adolescents. METHOD: In total, 182 healthy adolescents (98 boys and 84 girls)
      aged between 12 and 18 years, enrolled in public and private schools in the city
      of Natal-RN, were evaluated using an MVD300 digital manometer (Globalmed(r))
      according to a standardized protocol. Statistical analysis was performed using
      SPSS Statistics 17.0 software, with a significance level of 5%. Data normality
      was verified using the Kolmogorov-Smirnov test, and descriptive analysis results
      were expressed as the mean and standard deviation. To verify the correlation
      between the MRP and the independent variables (age, weight, height and sex), the
      Pearson correlation test was used. To obtain the prediction equations, stepwise
      multiple linear regression was used. RESULTS: The variables height, weight and
      sex were correlated to MRP. However, weight and sex explained part of the
      variability of MRP, and the regression analysis in this study indicated that
      these variables contributed significantly in predicting maximal inspiratory
      pressure, and only sex contributed significantly to maximal expiratory pressure.
      CONCLUSION: This study provides reference values and two models of prediction
      equations for maximal inspiratory and expiratory pressures and sets the necessary
      normal lower limits for the assessment of the respiratory muscle strength of
      Brazilian adolescents.

PMID- 23966140
TI  - Chester step test: assessment of functional capacity and magnitude of
      cardiorespiratory response in patients with COPD and healthy subjects.
AB  - BACKGROUND: the assessment of functional capacity in patients with chronic
      obstructive pulmonary disease (COPD) has been performed by simple and easy to
      apply methods that mimic everyday activities, such as the Chester step test
      (TChester). OBJECTIVES: to investigate whether TChester is able to differentiate
      functional capacity and the magnitude of cardiorespiratory response of patients
      with COPD from healthy subjects; and to compare it with the cardiorespiratory
      response induced by shuttle test (TShuttle) and six-minute walk test (6MWT).
      METHOD: 10 patients with COPD (64+/-10 years, and forced expiratory volume at the
      first second - FEV1 38.1+/-11.8% predicted) and 10 healthy subjects (63+/-7
      years, and FEV1 of 95.8+/-18.0% predicted) underwent evaluation of pulmonary
      function, functional status and capacity (6MWT, TShuttle and TChester). RESULTS:
      COPD patients had worst performance in all tests, when compared to healthy
      subjects (TChester 2,1+/-0,9 vs. 4,1+/-1,1 completed levels; TC6min: 435+/-105,1
      vs. 593+/-87,3 m; TShuttle 251+/-84,6 vs. 436+/-55,4 m; p<0.05). TChester
      correlated with TShuttle and 6MWT (r =0.67 and 0.83, respectively, p<0.05). There
      were no differences in heart rate and dyspnea in TChester levels between groups
      (p>0.05). SpO2 was lower in COPD patients since the first TChester level
      (p<0.05). CONCLUSION: TChester is valid in the assessment of functional capacity
      of COPD patients, being able to distinguish them from healthy subjects, inducing
      similar cardiovascular demand and greater desaturation in COPD patients.

PMID- 23966141
TI  - Late morbidity in upper limb function and quality of life in women after breast
      cancer surgery.
AB  - BACKGROUND: Breast cancer is the most common malignancy in Brazilian women. In
      recent years, there has been great progress in and an increasing number of breast
      conserving surgical techniques; however, immediate or late morbidity after
      surgery, in the form of functional impairment and pain, remains a significant
      clinical problem. OBJECTIVE: To investigate the relationship between late upper
      limb functional impairment and the quality of life in women subjected to breast
      cancer surgery. METHOD: A total of 81 women participated in the study, with the
      length of time since surgery ranging from one to five years. A survey of upper
      limb complaints reported by patients was conducted, and the questionnaires
      Disabilities of the Arm, Shoulder, and Hand (DASH) and the European Organization
      for Research and Treatment of Cancer (EORTC QLQC-30 and BR23) were applied.
      RESULTS: The correlation between the DASH score and the length of time since
      surgery determined that the longer the time since surgery, the greater the
      difficulties in functionality of the upper limb (r=0.459; p<0.0001). A
      statistically significant correlation was observed between the DASH score and
      health-related quality of life. CONCLUSION: Late functional impairment had a
      significant impact on upper limb function in everyday life and health-related
      quality of life for women who underwent breast cancer surgery.

PMID- 23966142
TI  - Reproducibility of step tests in patients with bronchiectasis.
AB  - BACKGROUND: The step test has been used to assess exercise capacity in patients
      with chronic respiratory disease; however, its use has not been described with
      regard to patients with bronchiectasis (BCT). OBJECTIVE: This study assessed the
      reliability of the Chester step test (CST) and the modified incremental step test
      (MIST) and also correlated these tests with pulmonary function, heart rate (HR),
      and distance walked during the 6-min walk test (6-MWT). METHOD: On separate days,
      17 patients randomly underwent two CSTs, two MISTs, and two 6-MWTs. Number of
      steps (NOSs), HR, and perceived exertion were recorded immediately before and
      after these tests. RESULTS: NOSs were similar across CSTs (124+/-65 and 125+/-67)
      and MISTs (158+/-83 and 156+/-76). Differences were not found across the CSTs and
      MISTs with regard to HR (138+/-25 bpm and 136+/-27 bpm), SpO2 (91+/-5% and 91+/
      3%), perceived exertion (dyspnea=4 [3-5] and 4 [2-4.5]) and fatigue (4 [2-6] and
      4 [3-5]). The CST was significantly briefer than the MIST (6.0+/-2.2 min and
      8.6+/-3.0 min) and had fewer associated NOS (125+/-67 and 158+/-83). NOSs were
      correlated with FEV1, the 6-MWD, and HR for both tests. CONCLUSIONS: The CST and
      MIST are reliable in patients with BCT. Patients tolerated the MIST more than the
      CST. Better lung function and 6-MWT scores predicted the greater NOSs and greater
      peak HR.

PMID- 23966143
TI  - Treatment time of ultrasound therapy interferes with the organization of collagen
      fibers in rat tendons.
AB  - BACKGROUND: The application time of therapeutic ultrasound is an infrequently
      studied dosimetric variable that affects tissue repair. OBJECTIVES: The aim of
      this study was to evaluate the effects of different treatment times of
      therapeutic ultrasound (US) on the organization of collagen fibers in the tendons
      of rats. METHOD: Forty Wistar rats were selected (300+/-45 g), and the rats were
      divided into five groups (n=8 for each group): Control, without tenotomy or any
      treatment; tenotomy group, with tenotomy and without treatment; US groups (US1,
      US2, and US3), subjected to tenotomy and treated with US for one, two, or three
      minutes per area of the transducer, respectively. The animals were sacrificed on
      the 12th post-operative day, and the tendons were surgically removed for analyses
      of the collagen fiber organization by means of birefringence analysis. RESULTS:
      The collagen fibers exhibited better aggregation and organization in the US3
      group compared with the tenotomy group (p<0.05). CONCLUSIONS: The findings
      suggest that US applied for three minutes per treated area improves the
      organization of collagen fibers during rat tendon repair.

PMID- 23966144
TI  - Translation, cross-cultural adaptation and analysis of the psychometric
      properties of the lower extremity functional scale (LEFS): LEFS- BRAZIL.
AB  - BACKGROUND: There is a lack of questionnaires in Brazilian Portuguese to evaluate
      patient-reported lower limb function. OBJECTIVE: To translate, cross-culturally
      adapt to the Brazilian population, and evaluate the psychometric properties of
      the Lower Extremity Functional Scale (LEFS). METHOD: The LEFS was translated by
      two independent assessors and back-translated to English. Then, the LEFS-Brazil
      was tested on 20 patients who answered the questionnaire in the cross-cultural
      adaptation phase. For the evaluation of the psychometric properties, 100 patients
      answered the questionnaire. The reliability was tested by two independent
      assessors. The Medical Outcomes Study 36-item from Health Survey (SF-36) was used
      as the criterion method for construct validity. The sensitivity to change was
      tested for four consecutive weeks. RESULTS: The internal consistency was alpha =
      0.96. The intra-observer reliability was CCI (intraclass correlation coefficient)
      = 0.96 and CCI interobserver = 0.98; the Bland and Altman mean difference (d)
      intra-observer = -1.52 and d interobserver = 0.46. The correlation between the
      LEFS and SF-36 in the first week was the following: physical function r=0.82,
      physical role r=0.57, emotional role r=0.43 and mental health r=0.33. The LEFS
      was responsive when comparing the mean of the first week to the second, third and
      fourth weeks and comparing the second to the fourth week. The cut-off point was
      11, and the area under the receiving operator curve was 0.96 95% CI [0.88;0.99],
      with sensitivity = 0.96, 1-specificity = 0 and standard error = 0.02. CONCLUSION:
      The LEFS-Brazil is reliable, valid and responsive.

PMID- 23966145
TI  - Interferential electrical stimulation improves peripheral vasodilatation in
      healthy individuals.
AB  - BACKGROUND: Interferential electrical stimulation (IES), which may be linked to
      greater penetration of deep tissue, may restore blood flow by sympathetic nervous
      modulation; however, studies have found no association between the frequency and
      duration of the application and blood flow. We hypothesized that 30 min of IES
      applied to the ganglion stellate region might improve blood flow redistribution.
      OBJECTIVES: The purpose of this study was to determine the effect of IES on
      metaboreflex activation in healthy individuals. METHOD: Interferential electrical
      stimulation or a placebo stimulus (same protocol without electrical output) was
      applied to the stellate ganglion region in eleven healthy subjects (age 25+/-1.3
      years) prior to exercise. Mean blood pressure (MBP), heart rate (HR), calf blood
      flow (CBF) and calf vascular resistance (CVR) were measured throughout exercise
      protocols (submaximal static handgrip exercise) and with recovery periods with or
      without postexercise circulatory occlusion (PECO+ and PECO -, respectively).
      Muscle metaboreflex control of calf vascular resistance was estimated by
      subtracting the area under the curve when circulation was occluded from the area
      under the curve from the AUC without circulatory occlusion. RESULTS: At peak
      exercise, increases in mean blood pressure were attenuated by IES (p<0.05), and
      the effect persisted under both the PECO+ and PECO- treatments. IES promoted
      higher CBF and lower CVR during exercise and recovery. Likewise, IES induced a
      reduction in the estimated muscle metaboreflex control (placebo, 21+/-5 units vs.
      IES, 6+/-3, p<0.01). CONCLUSION: Acute application of IES prior to exercise
      attenuates the increase in blood pressure and vasoconstriction during exercise
      and metaboreflex activation in healthy subjects.

PMID- 23966146
TI  - Body composition, muscle strength and quality of active elderly women according
      to the distance covered in the 6-minute walk test.
AB  - BACKGROUND: Changes arising from the aging process, particularly changes in body
      composition, contribute to the functional decline of the elderly. OBJECTIVE: To
      compare the body composition and muscle strength, mobility and quality in active
      elderly women according to the distance walked during the 6-minute walk test
      (6MWT). METHOD: The study included 77 active elderly women aged 65 to 80 years,
      who were divided into tertiles (A, B and C) according to the distance covered in
      the 6MWT. We performed anthropometric and clinical evaluations. Body composition
      was determined by dual energy X-ray absorptiometry (DXA). Handgrip strength (HGS)
      was measured with a portable dynamometer (Saehan), and knee extension strength
      (KES) was measured with the one repetition maximum test (1-RM). Functional
      mobility was assessed by the Timed Up and Go (TUG) test, and body balance was
      assessed by the Berg Balance Scale (BBS). Muscle quality was defined by the ratio
      between muscle strength (kgf) and muscle mass (kg). RESULTS: The group that
      walked the shortest distance in the 6MWT had a higher BMI (A=30.8+/-7.0, B=27.2+/
      4.2 and C=25.9+/-3.5 kg/m2), greater amount of fat mass (A=31.3+/-10.7, B=25.9+/
      6.7 and C=23.81+/-6.46 kg) lower HGS (A=21.8+/-5.1, B=22.1+/-3.5 and C=25.5+/-5.1
      kgf), lower knee extension strength (A=30.6+/-10.9, B=40.4+/-12.5 and C=47.2+/
      10.1 kgf), lower arm muscle quality (A=10.1+/-3.7, B=11.6+/-2 and C=12.7+/-2.2
      kg) and lower leg muscle quality (A=1.78+/-1, B=2.84+/-0.98 and C=3.31+/-0.77
      kg). There was no significant difference between muscle mass (p=0.25) and lean
      mass (p=0.26). CONCLUSION: Body fat has a negative influence on functional
      performance, even among active elderly women.

PMID- 23966147
TI  - Functional and cognitive changes in community-dwelling elderly: longitudinal
      study.
AB  - BACKGROUND: The relationship between aging and increased life expectancy in the
      overall population likely contributes to a higher frequency rate and incidence of
      illnesses and functional disabilities. Physical dependence and cognitive
      impairment might hinder the performance of activities and result in an overload
      of care duties for the patient's family and the healthcare system. OBJECTIVE: The
      aim of this study was to compare the functional and cognitive changes exhibited
      by the elderly over a 6-month period. METHOD: This longitudinal and observational
      study was conducted in a sample of 167 elderly people, who were selected from the
      database of the Network of Studies on Frailty in Brazilian Elderly, Universidade
      Federal de Minas Gerais - UFMG. The participants submitted to the Mini Mental
      State Examination (MMSE), Katz Index, Lawton and Brody's scale and responded to
      items on Advanced Activities of Daily Living (AADLs). We analyzed the data using
      multivariate regression models. RESULTS: The participants' functional capacity
      exhibited reduced performance of specific instrumental activities of daily living
      (IADLs), p=0.002, and basic activities of daily living (BADLs), p=0.038. Living
      alone (odds ratio (OR), 2.53; 95% confidence interval (CI), 1.09-5.87) and work
      status (OR, 2.52; 95% CI, 1.18-5.41) were associated with changes in the IADLs.
      The scores in the AADL scale (p=0.163) and MMSE (p=0.059) did not exhibit any
      significant difference during the study period. The participants with better
      cognitive function were more independent in their performance of AADLs and IADLs.
      CONCLUSION: The results depict specific patterns of loss and stability of
      functional capacity in community-dwelling elderly.

PMID- 23966148
TI  - 30 degrees  inclination in handles of plastic boxes can reduce postural and
      muscular workload during handling.
AB  - BACKGROUND: The handling of materials, which occurs in the industrial sector, is
      associated with lesions on the lumbar spine and in the upper limbs. Inserting
      handles in industrial boxes is a way to reduce work-related risks. Although the
      position and angle of the handles are significant factors in comfort and safety
      during handling, these factors have rarely been studied objectively. OBJECTIVE:
      To compare the handling of a commercial box and prototypes with handles and to
      evaluate the effects on upper limb posture, muscle electrical activity, and
      perceived acceptability using different grips while handling materials from
      different heights. METHOD: Thirty-seven healthy volunteers evaluated the handles
      of prototypes that allowed for changes in position (top and bottom) and angle (0
      degrees , 15 degrees , and 30 degrees ). Wrist, elbow, and shoulder movements
      were evaluated using electrogoniometry and inclinometry. The muscle electrical
      activity in the wrist extensors, biceps brachii, and the upper portion of the
      trapezius was measured using a portable electromyographer. The recorded data on
      muscle movements and electrical activity were synchronized. Subjective
      evaluations of acceptability were evaluated using a visual analog scale. RESULTS
      AND CONCLUSIONS: The prototypes with handles at a 30 degrees  angle produced the
      highest acceptability ratings, more neutral wrist positions, lower levels of
      electromyographic activity for the upper trapezius, and lower elevation angles
      for the arms. The different measurement methods were complementary in evaluating
      the upper limbs during handling.

PMID- 23966149
TI  - A new connection between VHL and cancer threads through progerin.

PMID- 23966150
TI  - How much is enough? Control of DNA double-strand break numbers in mouse meiosis.

PMID- 23966151
TI  - Prolyl isomerization: a new PIN code for DSB repair.

PMID- 23966152
TI  - The decapping scavenger enzyme DCS-1: a new modulator of miRNA turnover.

PMID- 23966153
TI  - Poised with purpose: cell plasticity enhances tumorigenicity.

PMID- 23966154
TI  - Hypothalamic inflammation and GnRH in aging development.

PMID- 23966155
TI  - Damage-induced aging and perpetual motion.

PMID- 23966157
TI  - The role of EMMPRIN expression in ovarian epithelial carcinomas.
AB  - PURPOSE: Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to
      involve in the invasion and metastasis of malignancies by regulating the
      expression of vascular endothelial growth factor (VEGF) and matrix
      metalloproteinases (MMPs) in stromal and cancer cells. The study aimed to clarify
      the role of EMMPRIN expression in tumorigenesis and progression of ovarian
      epithelial carcinomas. METHODS: EMMPRIN siRNA were transfected into ovarian
      carcinoma cells with the phenotypes and their related molecules examined. EMMPRIN
      expression was determined in ovarian normal tissue, benign and borderline tumors,
      and epithelial carcinomas by real-time PCR, western blot, and
      immunohistochemistry. RESULTS: EMMPRIN siRNA treatment resulted in a lower
      growth, G 1 arrest, apoptotic induction, decreased migration, and invasion. The
      transfectants showed reduced expression of Wnt5a, Akt, p70s6k, Bcl-xL, survivin,
      VEGF, and MMP-9 than mock and control cells at both mRNA and protein levels.
      According to real-time PCR and western blot, EMMPRIN mRNA or protein level was
      higher in ovarian borderline tumor and carcinoma than normal ovary and benign
      tumors (P<0.05), and positively correlated with dedifferentiation and FIGO
      staging (P<0.05). Immunohistochemically, EMMPRIN expression was positively
      correlated with FIGO staging, dedifferentiation, Ki-67 expression, the lower
      cumulative and relapse-free survival rate (P<0.05). CONCLUSIONS: Upregulated
      expression of EMMPRIN protein and mRNA might be involved in the pathogenesis,
      differentiation, and progression of ovarian carcinomas, possibly by modulating
      cellular events, such as proliferation, cell cycle, apoptosis, migration, and
      invasion.

PMID- 23966156
TI  - DNA repair pathways in human multiple myeloma: role in oncogenesis and potential
      targets for treatment.
AB  - Every day, cells are faced with thousands of DNA lesions, which have to be
      repaired to preserve cell survival and function. DNA repair is more or less
      accurate and could result in genomic instability and cancer. We review here the
      current knowledge of the links between molecular features, treatment, and DNA
      repair in multiple myeloma (MM), a disease characterized by the accumulation of
      malignant plasma cells producing a monoclonal immunoglobulin. Genetic instability
      and abnormalities are two hallmarks of MM cells and aberrant DNA repair pathways
      are involved in disease onset, primary translocations in MM cells, and MM
      progression. Two major drugs currently used to treat MM, the alkylating agent
      Melphalan and the proteasome inhibitor Bortezomib act directly on DNA repair
      pathways, which are involved in response to treatment and resistance. A better
      knowledge of DNA repair pathways in MM could help to target them, thus improving
      disease treatment. 

PMID- 23966158
TI  - Histone H2AX suppresses translocations in lymphomas of EMU-c-Myc transgenic mice
      that contain a germline amplicon of tumor-promoting genes.
AB  - The DNA damage response (DDR) can restrain the ability of oncogenes to cause
      genomic instability and drive malignant transformation. The gene encoding the
      histone H2AX DDR factor maps to 11q23, a region frequently altered in human
      cancers. Since H2ax functions as a haploinsufficient suppressor of B lineage
      lymphomas with c-Myc amplification and/or translocation, we determined the impact
      of H2ax expression on the ability of deregulated c-Myc expression to cause
      genomic instability and drive transformation of B cells. Neither H2ax deficiency
      nor haploinsufficiency affected the rate of mortality of EMU-c-Myc mice from B
      lineage lymphomas with genomic deletions and amplifications. Yet H2ax functioned
      in a dosage-dependent manner to prevent unbalanced translocations in EMU-c-Myc
      tumors, demonstrating that H2ax functions in a haploinsufficient manner to
      suppress allelic imbalances and limit molecular heterogeneity within and among
      EMU-c-Myc lymphomas. Regardless of H2ax copy number, all EMU-c-Myc tumors
      contained identical amplification of chromosome 19 sequences spanning 20 genes.
      Many of these genes encode proteins with tumor-promoting activities, including
      Cd274, which encodes the PD-L1 programmed death ligand that induces T cell
      apoptosis and enables cancer cells to escape immune surveillance. This amplicon
      was in non-malignant B and T cells and non-lymphoid cells, linked to the EMU-c
      Myc transgene, and associated with overexpression of PD-L1 on non-malignant B
      cells. Our data demonstrate that, in addition to deregulated c-Myc expression,
      non-malignant B lineage lymphocytes of EMU-c-Myc transgenic mice may have
      constitutive amplification and increased expression of other tumor-promoting
      genes. 

PMID- 23966159
TI  - Combined effects of PI3K and SRC kinase inhibitors with imatinib on intracellular
      calcium levels, autophagy, and apoptosis in CML-PBL cells.
AB  - Imatinib induces a complete cytogenetic regression in a large percentage of
      patients affected by chronic myeloid leukemia (CML) until mutations in the kinase
      domain of BCR-ABL appear. Alternative strategies for CML patients include the
      inhibition of phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of
      rapamycin (mTOR) pathway, which is constitutively activated in leukemia cells and
      seems important for the regulation of cell proliferation, viability, and
      autophagy. In this study, we verified the effect of imatinib mesylate (IM), alone
      or in association with LY294002 (LY) (a specific PI3K protein tyrosine kinase
      inhibitor) or 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine
      (PP1) (a Src tyrosine kinase inhibitor), on viability, intracellular calcium
      mobilization, apoptosis, and autophagy, in order to verify possible mechanisms of
      interaction. Our data demonstrated that PP1 and LY interact synergistically with
      IM by inducing apoptosis and autophagy in Bcr/Abl+ leukemia cells and this
      mechanism is related to the stress of the endoplasmic reticulum (ER). Our
      findings suggest a reasonable relationship between apoptotic and autophagic
      activity of tyrosine kinase inhibitors (TKIs) and the functionality of smooth ER
      Ca (2+)-ATPase and inositol triphosphate receptors, independently of
      intracellular calcium levels. Therapeutic strategies combining imatinib with PI3K
      and/or Src kinase inhibitors warrant further investigations in Bcr/Abl+
      malignancies, particularly in the cases of imatinib mesylate-resistant disease. 

PMID- 23966160
TI  - Protein phosphatase 4 is phosphorylated and inactivated by Cdk in response to
      spindle toxins and interacts with gamma-tubulin.
AB  - Many pharmaceuticals used to treat cancer target the cell cycle or mitotic
      spindle dynamics, such as the anti-tumor drug, paclitaxel, which stabilizes
      microtubules. Here we show that, in cells arrested in mitosis with the spindle
      toxins, nocodazole, or paclitaxel, the endogenous protein phosphatase 4 (Ppp4)
      complex Ppp4c-R2-R3A is phosphorylated on its regulatory (R) subunits, and its
      activity is inhibited. The phosphorylations are blocked by roscovitine,
      indicating that they may be mediated by Cdk1-cyclin B. Endogenous Ppp4c is
      enriched at the centrosomes in the absence and presence of paclitaxel,
      nocodazole, or roscovitine, and the activity of endogenous Ppp4c-R2-R3A is
      inhibited from G 1/S to the G 2/M phase of the cell cycle. Endogenous gamma
      tubulin and its associated protein, gamma-tubulin complex protein 2, both of
      which are essential for nucleation of microtubules at centrosomes, interact with
      the Ppp4 complex. Recombinant gamma-tubulin can be phosphorylated by Cdk1-cyclin
      B or Brsk1 and dephosphorylated by Ppp4c-R2-R3A in vitro. The data indicate that
      Ppp4c-R2-R3A regulates microtubule organization at centrosomes during cell
      division in response to stress signals such as spindle toxins, paclitaxel, and
      nocodazole, and that inhibition of the Ppp4 complex may be advantageous for
      treatment of some cancers. 

PMID- 23966161
TI  - Lineage specification in the fly nervous system and evolutionary implications.
AB  - Over the last decades, it has become clear that glia are multifunctional and
      plastic cells endowed with key regulatory roles. They control the response to
      developmental and/or pathological signals, thereby affecting neural
      proliferation, remodeling, survival, and regeneration. It is, therefore,
      important to understand the biology of these cells and the molecular mechanisms
      controlling their development/activity. The fly community has made major
      breakthroughs by characterizing the bases of gliogenesis and function. Here we
      describe the regulation and the role of the fly glial determinant. Then, we
      discuss the impact of the determinant in cell plasticity and differentiation.
      Finally, we address the conservation of this pathway across evolution. 

PMID- 23966163
TI  - The role of Aurora A in hypoxia-inducible factor 1alpha-promoting malignant
      phenotypes of hepatocelluar carcinoma.
AB  - Overexpression of both hypoxia-inducible factor 1alpha (HIF-1alpha) and Aurora A
      has been found in hepatocellular carcinoma (HCC). However, whether HIF-1alpha and
      Aurora A synergistically promote malignant phenotypes of HCC cells is unknown.
      The purpose of this study was to investigate the roles and functional correlation
      of HIF-1alpha and Aurora A in HCC progression. Immunohistochemistry was performed
      to detect HIF-1alpha and Aurora A protein expression in 55 primary HCC and
      corresponding non-tumor tissues and their clinical significance. Gene knockout
      technology using short hairpin RNA (shRNA) was used to knockdown expression of
      HIF-1alpha or Aurora A and analyze their effects on malignant phenotypes of HCC
      cells. The transcriptional regulation of Aurora A by HIF-1alpha and the possible
      downstream molecular signaling pathways were also determined. Results showed that
      hypoxia could induce the increased expression of HIF-1alpha and Aurora A in HCC
      cells. Also, shRNA-mediated HIF-1alpha downregulation could lead to the decreased
      Aurora A expression and inhibition of growth or invasion in HCC cells. Moreover,
      HIF-1alpha could transcriptionally regulate Aurora A expression by binding to
      hypoxia-responsive elements in the Aurora A promoter and recruiting the
      coactivator-p300/CBP. Additionally, shRNA-mediated Aurora A knockdown could mimic
      the effects of HIF-1alpha downregulation on phenotypes of HCC cells, and
      overexpression of Aurora A could partially rescue the phenotypical changes of HCC
      cells induced by HIF-1alpha downregulation. Further research indicated that
      activation of Akt and p38-MAPK signaling pathways mediated the downstream effects
      of HIF-1alpha and Aurora A in HCC cells under hypoxic condition. Taken together,
      our findings indicated that Aurora A might be a key regulator of HIF-1alpha
      promoting malignant phenotypes of HCC by activation of Akt and p38-MAPK signaling
      pathways.

PMID- 23966165
TI  - Phosphoproteomics taken to heart.

PMID- 23966164
TI  - Loss of the proteins Bak and Bax prevents apoptosis mediated by histone
      deacetylase inhibitors.
AB  - Burkitt lymphoma is characterized by deregulation of c-myc, and therapies
      targeting c-myc are under investigation as treatments. Histone deacetylase
      inhibitors are known to abrogate c-myc expression, leading us to examine their
      effect in a series of Burkitt lymphoma cell lines. While treatment with
      romidepsin, panobinostat, vorinostat, or belinostat for 48 h resulted in complete
      cell death in the Ramos and ST486 lines, CA46 and DG75 cells were resistant. In
      parallel studies, CA46 and DG75 cells were also insensitive to 48 h treatment
      with the Aurora kinase inhibitors (AKIs) MLN8237 (alisertib), VX-680
      (tozasertib), or ZM447439. Bax knockdown is known to lead to HDI resistance, and
      we found that loss of Bax or both Bak and Bax correlated with resistance to both
      AKIs and HDIs in the Burkitt cell lines. As proof-of-concept to evaluate the
      contribution of Bax and Bak to HDI-mediated apoptosis, we found that apoptosis
      was unaffected in HCT-116 colon carcinoma cells lacking Bak, blunted in cells
      lacking Bax, and nearly completely abrogated in cells lacking both Bak and Bax
      compared with wild-type cells. To explore potential clinical variations in Bak
      and Bax expression, a series of samples from 16 patients diagnosed with Burkitt
      lymphoma was examined. While the majority of samples were positive for both Bak
      and Bax, some (3/16) expressed low levels of both proteins. We thus conclude that
      HDI-mediated and AKI-mediated apoptosis requires mitochondrial engagement, and
      that baseline Bax and Bak expression may serve as biomarkers for patients with
      Burkitt lymphoma likely to respond to HDI treatment. 

PMID- 23966166
TI  - ZNF365 promotes stalled replication forks recovery to maintain genome stability.
AB  - The ZNF365 locus is associated with breast cancer risk in carriers of mutated
      BRCA1 and BRCA2, which are important molecules required for DNA damage response.
      Previously, we demonstrated that ZNF365 is necessary for timely resolution of
      replication intermediates of genomic fragile sites and, thus, for suppression of
      genomic instability; however, the mechanism underlying the function of ZNF365 on
      damaged DNA and stalled replication forks remains unknown. Here, we demonstrate
      that ZNF365 is induced by DNA double-strand break (DSB) signals, is involved in
      the homologous recombination (HR) repair pathway, and maintains genome integrity
      during DNA replication. On the mechanistic level, ZNF365 interacts with poly(ADP
      ribose) polymerase (PARP) 1 to tether MRE11 to the DNA end resection site. Loss
      of ZNF365 results in delayed mitotic progression and exit due to increased
      replication stress, ultimately leading to cytokinesis failure, re-duplication of
      centrosomes, and increased aneuploidy. Collectively, these results suggest an HR
      repair-dependent function of ZNF365 in preventing genomic instability. 

PMID- 23966167
TI  - Comparison of efficacy of Salmonella typhimurium A1-R and chemotherapy on stem
      like and non-stem human pancreatic cancer cells.
AB  - The XPA1 human pancreatic cancer cell line is dimorphic, with spindle stem-like
      cells and round non-stem cells. We report here the in vitro IC 50 values of stem
      like and non-stem XPA1 human pancreatic cells cells for: (1) 5-fluorouracil (5
      FU), (2) cisplatinum (CDDP), (3) gemcitabine (GEM), and (4) tumor-targeting
      Salmonella typhimurium A1-R (A1-R). IC 50 values of stem-like XPA1 cells were
      significantly higher than those of non-stem XPA1 cells for 5-FU (P = 0.007) and
      CDDP (P = 0.012). In contrast, there was no difference between the efficacy of A1
      R on stem-like and non-stem XPA1 cells. In vivo, 5-FU and A1-R significantly
      reduced the tumor weight of non-stem XPA1 cells (5-FU; P = 0.028; A1-R; P =
      0.011). In contrast, only A1-R significantly reduced tumor weight of stem-like
      XPA1 cells (P = 0.012). The combination A1-R with 5-FU improved the antitumor
      efficacy compared with 5-FU monotherapy on the stem-like cells (P = 0.004). The
      results of the present report indicate A1-R is a promising therapy for chemo
      resistant pancreatic cancer stem-like cells. 

PMID- 23966168
TI  - Revealing targeted therapeutic opportunities in triple-negative breast cancers: a
      new strategy.

PMID- 23966169
TI  - Mitochondrial p53 mediates a transcription-independent regulation of cell
      respiration and interacts with the mitochondrial F1F0-ATP synthase.
AB  - We and others previously reported that endogenous p53 can be located at
      mitochondria in the absence of stress, suggesting that p53 has a role in the
      normal physiology of this organelle. The aim of this study was to characterize in
      unstressed cells the intramitochondrial localization of p53 and identify new
      partners and functions of p53 in mitochondria. We find that the
      intramitochondrial pool of p53 is located in the intermembrane space and the
      matrix. Of note, unstressed HCT116 p53(+/+) cells simultaneously show increased
      O2 consumption and decreased mitochondrial superoxide production compared with
      their p53-null counterpart. This data was confirmed by stable H1299 cell lines
      expressing low levels of p53 specifically targeted to the matrix. Using
      immunoprecipitation and mass spectrometry, we identified the oligomycin
      sensitivity-conferring protein (OSCP), a subunit of the F1F0-ATP synthase
      complex, as a new partner of endogenous p53, specifically interacting with p53
      localized in the matrix. Interestingly, this interaction seems implicated in
      mitochondrial p53 localization. Moreover, p53 localized in the matrix promotes
      the assembly of F1F0-ATP synthase. Taking into account that deregulations of
      mitochondrial respiration and reactive oxygen species production are tightly
      linked to cancer development, we suggest that mitochondrial p53 may be an
      important regulator of normal mitochondrial and cellular physiology, potentially
      exerting tumor suppression activity inside mitochondria. 

PMID- 23966170
TI  - Saccharomyces cerevisiae Dma proteins participate in cytokinesis by controlling
      two different pathways.
AB  - Cytokinesis completion in the budding yeast S. cerevisiae is driven by tightly
      regulated pathways, leading to actomyosin ring contraction coupled to plasma
      membrane constriction and to centripetal growth of the primary septum,
      respectively. These pathways can partially substitute for each other, but their
      concomitant inactivation leads to cytokinesis block and cell death. Here we show
      that both the lack of the functionally redundant FHA-RING ubiquitin ligases Dma1
      and Dma2 and moderate Dma2 overproduction affect actomyosin ring contraction as
      well as primary septum deposition, although they do not apparently alter cell
      cycle progression of otherwise wild-type cells. In addition, overproduction of
      Dma2 impairs the interaction between Tem1 and Iqg1, which is thought to be
      required for AMR contraction, and causes asymmetric primary septum deposition as
      well as mislocalization of the Cyk3-positive regulator of this process. In
      agreement with these multiple inhibitory effects, a Dma2 excess that does not
      cause any apparent defect in wild-type cells leads to lethal cytokinesis block in
      cells lacking the Hof1 protein, which is essential for primary septum formation
      in the absence of Cyk3. Altogether, these findings suggest that the Dma proteins
      act as negative regulators of cytokinesis. 

PMID- 23966171
TI  - SUMOylation of p53 mediates interferon activities.
AB  - There is growing evidence that many host proteins involved in innate and
      intrinsic immunity are regulated by SUMOylation, and that SUMO contributes to the
      regulatory process that governs the initiation of the type I interferon (IFN)
      response. The tumor suppressor p53 is a modulator of the IFN response that plays
      a role in virus-induced apoptosis and in IFN-induced senescence. Here we
      demonstrate that IFN treatment increases the levels of SUMOylated p53 and induces
      cellular senescence through a process that is partially dependent upon
      SUMOylation of p53. Similarly, we show that vesicular stomatitis virus (VSV)
      infection induces p53 SUMOylation, and that this modification favors the control
      of VSV replication. Thus, our study provides evidence that IFN signaling induces
      p53 SUMOylation, which results in the activation of a cellular senescence program
      and contributes to the antiviral functions of interferon. 

PMID- 23966172
TI  - Regulation of lysosome biogenesis and functions in osteoclasts.
AB  - In order to resorb the mineralized bone extracellular matrix, the osteoclast
      relies on the generation of a resorption lacuna characterized by the presence of
      specific proteases and a low pH. Hence, bone resorption by osteoclasts is highly
      dependent on lysosomes, the organelles specialized in intra- and extracellular
      material degradation. This is best illustrated by the fact that multiple forms of
      human osteopetrosis are caused by mutations in genes encoding for lysosomal
      proteins. Yet, until recently, the molecular mechanisms regulating lysosomal
      biogenesis and function in osteoclasts were poorly understood. Here we review the
      latest developments in the study of lysosomal biogenesis and function in
      osteoclasts with an emphasis on the transcriptional control of these processes. 

PMID- 23966173
TI  - Pirh2: an E3 ligase with central roles in the regulation of cell cycle, DNA
      damage response, and differentiation.
AB  - Ubiquitylation is currently recognized as a major posttranslational modification
      that regulates diverse cellular processes. Pirh2 is a ubiquitin E3 ligase that
      regulates the turnover and functionality of several proteins involved in cell
      proliferation and differentiation, cell cycle checkpoints, and cell death. Here
      we review the role of Pirh2 as a regulator of the DNA damage response through the
      ubiquitylation of p53, Chk2, p73, and PolH. By ubiquitylating these proteins,
      Pirh2 regulates cell cycle checkpoints and cell death in response to DNA double
      strand breaks or the formation of bulky DNA lesions. We also discuss how Pirh2
      affects cell proliferation and differentiation in unstressed conditions through
      ubiquitylation and degradation of c-Myc, p63, and p27(kip1). Finally, we link
      these different functions of Pirh2 to its role as a tumor suppressor in mice and
      as a prognosis marker in various human cancer subtypes. 

PMID- 23966174
TI  - Blood pressure targets in the treatment of high blood pressure: a reappraisal of
      the J-shaped phenomenon.
AB  - The risk that lowering blood pressure (BP) excessively increases the incidence of
      cardiovascular disease-the J-shaped phenomenon-has been a matter of concern
      endorsed by many experts, particularly in patients with coronary heart disease
      and diabetes. The results of the Action to Control Cardiovascular Risk in Type 2
      Diabetes (ACCORD) trial strengthened the idea that it may be futile to lower BP
      more intensively in patients with diabetes. Nevertheless, there seems to be no
      direct J-shaped relation between BP-lowering treatment and outcome. Patients with
      normal or low BP and high or very high cardiovascular risk could have their BP
      reduced further by treatment. Placebo-controlled clinical trials of BP-lowering
      agents in patients with BP within normal values and concomitant cardiovascular
      disease demonstrated consistent reduction of recurrent and newer cardiovascular
      events. The use of BP agents in such conditions, as in patients with coronary
      artery disease, heart failure, diabetes and in patients recovered from a stroke
      has been endorsed by guidelines. Although is likely that there is a J-shaped
      relationship of BP with outcomes in cohort studies, clinical trials that tested
      more intensive versus standard goals and clinical trials done with patients with
      low BP demonstrated that the J-shaped phenomenon should not be a concern in the
      treatment of high BP. 

PMID- 23966175
TI  - A rapid, direct, quantitative, and label-free detector of cardiac biomarker
      troponin T using near-infrared fluorescent single-walled carbon nanotube sensors.
AB  - Patients with chest pain account for 10% of US emergency room visits according to
      data from the Center for Disease Control and Prevention (2013). For triage of
      these patients, cardiac biomarkers troponin I and T are endorsed as standard
      indicators for acute myocardial infarction (AMI, or heart attack). Thus, there is
      significant interest in developing a rapid, point-of-care (POC) device for
      troponin detection. In this work, a rapid, quantitative, and label-free assay,
      which is specific for cardiac troponin T (cTnT) detection, using fluorescent
      single-walled carbon nanotubes (SWCNTs), is demonstrated. Chitosan-wrapped carbon
      nanotubes are cross-linked to form a thin gel that is further functionalized with
      nitrilotriacetic acid (NTA) moieties. Upon chelation of Ni(2+) , the Ni(2+) -NTA
      group binds to a hexa-histidine-modified troponin antibody, which specifically
      recognizes the target protein, troponin T. As the troponin T binds to the
      antibody, the local environment of the sensor changes, allowing direct troponin
      detection through intensity changes in SWCNT bandgap fluorescence. This platform
      represents the first near-infrared SWCNT sensor array for cTnT detection.
      Detection can be completed within 5 min, demonstrating a linear response to cTnT
      concentration and an experimental detection limit of 100 ng mL(-1) (2.5 nm). This
      platform provides a promising new tool for POC AMI detection in the future.
      Moreover, the work presents two new methods of quantifying the number of amines
      and carboxylic groups, respectively, in a carbon hydrogel matrices. 

PMID- 23966177
TI  - Preventable errors with nonopioid analgesics and antiemetic drugs may increase
      burden in surgical pediatric patients.
AB  - INTRODUCTION: Many hospitalized patients are affected by medication errors (MEs)
      that may cause discomfort, harm, and even death. Especially, children are
      considered to be at high risk of experiencing harm due to MEs. More insight into
      the prevalence, type, and severity of harm caused by MEs could help reduce the
      frequency of these harmful events. The primary objectives of our study were to
      establish the prevalence of different types of MEs and the severity of harm
      caused by MEs in hospitalized children from birth to 18 years of age. In
      addition, we investigated correlations between harmful MEs and characteristics of
      the collected data from 426 hospitalized children admitted, and the medication
      process. METHODS: In this cross-sectional study, we identified MEs by reviewing
      clinical records, making direct observations, monitoring pharmacy logs, and
      reviewing voluntary incident reports. Subsequently, the MEs were classified
      according to type of error, medication group and stage of the medication process.
      Pediatricians rated the severity of the observed harm. RESULTS: We collected data
      from 426 hospitalized children admitted during August to October 2011. A total of
      322 MEs were identified, of which 39 caused patient harm. Harmful events were
      mainly because of wrong time (41%). Pediatricians rated the observed harm as
      minor in 77% of the incidents and significant in 23%. None of the harmful MEs
      resulted in permanent harm or was considered life-threatening or fatal. Patients
      admitted for a surgical procedure were at higher risk for a harmful event
      compared with patients admitted for nonsurgical reasons (adjusted odds ratio
      2.79, 95% confidence interval; 1.35-5.80). Nonopioid analgesics and antiemetic
      drugs accounted for 67% of the harmful MEs. Harmful MEs occurred most frequently
      during medication prescription (28%) and administration (62%). CONCLUSION:
      Surgical pediatric patients seem to be at high risk for harmful MEs. Although the
      harm was considered minor in most cases, it still caused discomfort for the
      patients, and the high prevalence is a source of concern. Interventions to
      prevent the MEs should focus on the prescription and administration of nonopioid
      analgesics and antiemetic drugs.

PMID- 23966178
TI  - Anxiety and quality of life of parents with children diagnosed with an anorectal
      malformation or Hirschsprung disease.
AB  - AIM: The aim of this study was to investigate the difference in anxiety and
      quality of life (QOL) between mothers and fathers of children with anorectal
      malformations (ARM) or Hirschsprung disease (HD). In addition, anxiety of parents
      of newborns was compared with parents of children in the age-group of 10 to 13
      years. METHODS: Parents of 44 patients with ARM or HD completed the World Health
      Organization Quality of Life (WHOQOL)-BREF (26 items) and the Spielberger State
      Trait Anxiety Inventory (STAI-trait 10 items, STAI-state 6 items). They were
      divided into two groups according to their children's age (0-4 years and 10-13
      years). RESULTS: Overall mothers scored significantly worse than fathers on state
      anxiety (p = 0.005). Trait anxiety was not significantly different between
      mothers and fathers. The psychological domain of the WHOQOL-BREF was
      significantly different between parents (p = 0.016), with mothers scoring worse.
      Dividing the group in newborns and school going children mothers of newborns
      showed significantly more state anxiety compared with fathers of newborns (p =
      0.016). In the group of older children, both anxiety and QOL were not
      significantly different between fathers and mothers. Comparing mothers of
      newborns with mothers of older children, the first group scored higher on state
      anxiety, but this difference was not significant (p = 0.138; 95% confidence
      interval, 0.535-3.717). CONCLUSIONS: Mothers of newborns have a higher level of
      anxiety than fathers of newborns with ARM or HD. When children with ARM or HD
      become older, this difference in anxiety between parents is not significant
      anymore. This may be explained by coping strategies.

PMID- 23966179
TI  - Experimental verification and investigation of disks scattering slab modes in
      metal-dielectric heterostructures.
AB  - A thin dielectric plate can support conventional slab modes such as leaky Fabry
      Perot, guided waves and radiation modes. When the plate is coated on a metallic
      subwavelength disk array, it can result in new confined modes, hereby named
      'disks scattering slab modes' (DSSMs). By use of a terahertz time-domain
      spectroscopy system, we experimentally verify the existence of two types of DSSMs
      in terahertz range: one we refer to as highly confined disks scattering Fabry
      Perot-like modes (DSFPMs) and the other as, weakly confined disks scattering
      radiation-like modes (DSRMs). Spectral characteristics of these confined modes
      are measured and numerically simulated. Particularly, based on the experimental
      results and a dipole-scattering model developed here, we show that the features
      of the DSFPMs can be tuned by changing the filling fraction of the disk array. We
      believe these results can make important contributions to the designs of new
      terahertz devices, including tunable absorbers and filters. 

PMID- 23966176
TI  - Predicting protein-DNA interactions by full search computational docking.
AB  - Protein-DNA interactions are essential for many biological processes. X-ray
      crystallography can provide high-resolution structures, but protein-DNA complexes
      are difficult to crystallize and typically contain only small DNA fragments.
      Thus, there is a need for computational methods that can provide useful
      predictions to give insights into mechanisms and guide the design of new
      experiments. We used the program DOT, which performs an exhaustive, rigid-body
      search between two macromolecules, to investigate four diverse protein-DNA
      interactions. Here, we compare our computational results with subsequent
      experimental data on related systems. In all cases, the experimental data
      strongly supported our structural hypotheses from the docking calculations: a
      mechanism for weak, nonsequence-specific DNA binding by a transcription factor, a
      large DNA-binding footprint on the surface of the DNA-repair enzyme uracil-DNA
      glycosylase (UNG), viral and host DNA-binding sites on the catalytic domain of
      HIV integrase, and a three-DNA-contact model of the linker histone bound to the
      nucleosome. In the case of UNG, the experimental design was based on the DNA
      binding surface found by docking, rather than the much smaller surface observed
      in the crystallographic structure. These comparisons demonstrate that the DOT
      electrostatic energy gives a good representation of the distinctive electrostatic
      properties of DNA and DNA-binding proteins. The large, favourably ranked clusters
      resulting from the dockings identify active sites, map out large DNA-binding
      sites, and reveal multiple DNA contacts with a protein. Thus, computational
      docking can not only help to identify protein-DNA interactions in the absence of
      a crystal structure, but also expand structural understanding beyond known
      crystallographic structures.

PMID- 23966180
TI  - A vision-based automated guided vehicle system with marker recognition for indoor
      use.
AB  - We propose an intelligent vision-based Automated Guided Vehicle (AGV) system
      using fiduciary markers. In this paper, we explore a low-cost, efficient vehicle
      guiding method using a consumer grade web camera and fiduciary markers. In the
      proposed method, the system uses fiduciary markers with a capital letter or
      triangle indicating direction in it. The markers are very easy to produce,
      manipulate, and maintain. The marker information is used to guide a vehicle. We
      use hue and saturation values in the image to extract marker candidates. When the
      known size fiduciary marker is detected by using a bird's eye view and Hough
      transform, the positional relation between the marker and the vehicle can be
      calculated. To recognize the character in the marker, a distance transform is
      used. The probability of feature matching was calculated by using a distance
      transform, and a feature having high probability is selected as a captured
      marker. Four directional signals and 10 alphabet features are defined and used as
      markers. A 98.87% recognition rate was achieved in the testing phase. The
      experimental results with the fiduciary marker show that the proposed method is a
      solution for an indoor AGV system. 

PMID- 23966181
TI  - Stroke damage detection using classification trees on electrical bioimpedance
      cerebral spectroscopy measurements.
AB  - After cancer and cardio-vascular disease, stroke is the third greatest cause of
      death worldwide. Given the limitations of the current imaging technologies used
      for stroke diagnosis, the need for portable non-invasive and less expensive
      diagnostic tools is crucial. Previous studies have suggested that electrical
      bioimpedance (EBI) measurements from the head might contain useful clinical
      information related to changes produced in the cerebral tissue after the onset of
      stroke. In this study, we recorded 720 EBI Spectroscopy (EBIS) measurements from
      two different head regions of 18 hemispheres of nine subjects. Three of these
      subjects had suffered a unilateral haemorrhagic stroke. A number of features
      based on structural and intrinsic frequency-dependent properties of the cerebral
      tissue were extracted. These features were then fed into a classification tree.
      The results show that a full classification of damaged and undamaged cerebral
      tissue was achieved after three hierarchical classification steps. Lastly, the
      performance of the classification tree was assessed using Leave-One-Out Cross
      Validation (LOO-CV). Despite the fact that the results of this study are limited
      to a small database, and the observations obtained must be verified further with
      a larger cohort of patients, these findings confirm that EBI measurements contain
      useful information for   assessing on the health of brain tissue after stroke and
      supports the hypothesis that classification features based on Cole parameters,
      spectral information and the geometry of EBIS measurements are useful to
      differentiate between healthy and stroke damaged brain tissue. 

PMID- 23966182
TI  - Advancements of data anomaly detection research in wireless sensor networks: a
      survey and open issues.
AB  - Wireless Sensor Networks (WSNs) are important and necessary platforms for the
      future as the concept "Internet of Things" has emerged lately. They are used for
      monitoring, tracking, or controlling of many applications in industry, health
      care, habitat, and military. However, the quality of data collected by sensor
      nodes is affected by anomalies that occur due to various reasons, such as node
      failures, reading errors, unusual events, and malicious attacks. Therefore,
      anomaly detection is a necessary process to ensure the quality of sensor data
      before it is utilized for making decisions. In this review, we present the
      challenges of anomaly detection in WSNs and state the requirements to design
      efficient and effective anomaly detection models. We then review the latest
      advancements of data anomaly detection research in WSNs and classify current
      detection approaches in five main classes based on the detection methods used to
      design these approaches. Varieties of the state-of-the-art models for each class
      are covered and their limitations are highlighted to provide ideas for potential
      future works. Furthermore, the reviewed approaches are compared and evaluated
      based on how well they meet the stated requirements. Finally, the general
      limitations of current approaches are mentioned and further research
      opportunities are suggested and discussed. 

PMID- 23966183
TI  - Characterization of the bell-shaped vibratory angular rate gyro.
AB  - The bell-shaped vibratory angular rate gyro (abbreviated as BVG) is a novel shell
      vibratory gyroscope, which is inspired by the Chinese traditional bell. It
      sensitizes angular velocity through the standing wave precession effect. The bell
      shaped resonator is a core component of the BVG and looks like the millimeter
      grade Chinese traditional bell, such as QianLong Bell and Yongle Bell. It is made
      of Ni43CrTi, which is a constant modulus alloy. The exciting element, control
      element and detection element are uniformly distributed and attached to the
      resonator, respectively. This work presents the design, analysis and
      experimentation on the BVG. It is most important to analyze the vibratory
      character of the bell-shaped resonator. The strain equation, internal force and
      the resonator's equilibrium differential equation are derived in the orthogonal
      curvilinear coordinate system. When the input angular velocity is existent on the
      sensitive axis, an analysis of the vibratory character is performed using the
      theory of thin shells. On this basis, the mode shape function and the simplified
      second order normal vibration mode dynamical equation are obtained. The coriolis
      coupling relationship about the primary mode and secondary mode is established.
      The methods of the signal processing and control loop are presented. Analyzing
      the impact resistance property of the bell-shaped resonator, which is compared
      with other shell resonators using the Finite Element Method, demonstrates that
      BVG has the advantage of a better impact resistance property. A reasonable means
      of installation and a prototypal gyro are designed. The gyroscopic effect of the
      BVG is characterized through experiments. Experimental results show that the BVG
      has not only the advantages of low cost, low power, long work life, high
      sensitivity, and so on, but, also, of a simple structure and a better impact
      resistance property for low and medium angular velocity measurements. 

PMID- 23966184
TI  - Measuring center of pressure signals to quantify human balance using multivariate
      multiscale entropy by designing a force platform.
AB  - To assess the improvement of human body balance, a low cost and portable
      measuring device of center of pressure (COP), known as center of pressure and
      complexity monitoring system (CPCMS), has been developed for data logging and
      analysis. In order to prove that the system can estimate the different magnitude
      of different sways in comparison with the commercial Advanced Mechanical
      Technology Incorporation (AMTI) system, four sway tests have been developed
      (i.e., eyes open, eyes closed, eyes open with water pad, and eyes closed with
      water pad) to produce different sway displacements. Firstly, static and dynamic
      tests were conducted to investigate the feasibility of the system. Then,
      correlation tests of the CPCMS and AMTI systems have been compared with four sway
      tests. The results are within the acceptable range. Furthermore, multivariate
      empirical mode decomposition (MEMD) and enhanced multivariate multiscale entropy
      (MMSE) analysis methods have been used to analyze COP data reported by the CPCMS
      and compare it with the AMTI system. The improvements of the CPCMS are 35% to 70%
      (open eyes test) and 60% to 70% (eyes closed test) with and without water pad.
      The AMTI system has shown an improvement of 40% to 80% (open eyes test) and 65%
      to 75% (closed eyes test). The results indicate that the CPCMS system can achieve
      similar results to the commercial product so it can determine the balance. 

PMID- 23966185
TI  - Nano-molar deltamethrin sensor based on electrical impedance of PAH/PAZO layer-by
      layer sensing films.
AB  - This work reports a novel deltamethrin (DM) sensor able to detect nano-molar
      concentrations in ethanol solutions. The sensing layer consists of a thin film,
      obtained via a layer-by-layer technique, from alternate adsorption of
      poly(allylamine chloride) (PAH) and poly[1-[4-(3-carboxy-4-hydroxyphenylazo)
      benzenesulfonamide)-1,2-ethanediyl]sodium salt] (PAZO) onto a solid support with
      interdigitaded gold electrodes. The sensor response, obtained from impedance
      spectroscopy measurements, was revealed to be linear with respect to the real
      part of impedance, taken at 100 Hz, when plotted as a function of the logarithm
      of deltamethrin molar concentrations in the micro- to nano-molar range. Sensor
      sensitivity was of 41.1 +/- 0.7 kOmega per decade of concentration for an
      immersion time above 2 min and the reproducibility is approximately 2% in a
      binary solution of ethanol and deltamethrin. The main insight of this work
      concerns to DM detection limits as the sensor revealed to be able to detect
      concentrations below 0.1 nM, a value which is significantly lower than any
      reported in the literature and close what is appropriate for in situ
      environmental contaminant detection. 

PMID- 23966186
TI  - Potential of on-line visible and near infrared spectroscopy for measurement of pH
      for deriving variable rate lime recommendations.
AB  - This paper aims at exploring the potential of visible and near infrared (vis-NIR)
      spectroscopy for on-line measurement of soil pH, with the intention to produce
      variable rate lime recommendation maps. An on-line vis-NIR soil sensor set up to
      a frame was used in this study. Lime application maps, based on pH predicted by
      vis-NIR techniques, were compared with maps based on traditional lab-measured pH.
      The validation of the calibration model using off-line spectra provided excellent
      prediction accuracy of pH (R2 = 0.85, RMSEP = 0.18 and RPD = 2.52), as compared
      to very good accuracy obtained with the on-line measured spectra (R2 = 0.81,
      RMSEP = 0.20 and RPD = 2.14). On-line predicted pH of all points (e.g., 2,160)
      resulted in the largest overall field virtual lime requirement (1.404 t), as
      compared to those obtained with 16 validation points off-line prediction (0.28
      t), on-line prediction (0.14 t) and laboratory reference measurement (0.48 t).
      The conclusion is that the vis-NIR spectroscopy can be successfully used for the
      prediction of soil pH and for deriving lime recommendations. The advantage of the
      on-line sensor over sampling with limited number of samples is that more detailed
      information about pH can be obtained, which is the reason for a higher but
      precise calculated lime recommendation rate. 

PMID- 23966187
TI  - Rapid online analysis of local feature detectors and their complementarity.
AB  - A vision system that can assess its own performance and take appropriate actions
      online to maximize its effectiveness would be a step towards achieving the long
      cherished goal of imitating humans. This paper proposes a method for performing
      an online performance analysis of local feature detectors, the primary stage of
      many practical vision systems. It advocates the spatial distribution of local
      image features as a good performance indicator and presents a metric that can be
      calculated rapidly, concurs with human visual assessments and is complementary to
      existing offline measures such as repeatability. The metric is shown to provide a
      measure of complementarity for combinations of detectors, correctly reflecting
      the underlying principles of individual detectors. Qualitative results on well
      established datasets for several state-of-the-art detectors are presented based
      on the proposed measure. Using a hypothesis testing approach and a newly
      acquired, larger image database, statistically-significant performance
      differences are identified. Different detector pairs and triplets are examined
      quantitatively and the results provide a useful guideline for combining detectors
      in applications that require a reasonable spatial distribution of image features.
      A principled framework for combining feature detectors in these applications is
      also presented. Timing results reveal the potential of the metric for online
      applications. 

PMID- 23966188
TI  - Continuous wavelet transform analysis of acceleration signals measured from a
      wave buoy.
AB  - Accelerometers, which can be installed inside a floating platform on the sea, are
      among the most commonly used sensors for operational ocean wave measurements. To
      examine the non-stationary features of ocean waves, this study was conducted to
      derive a wavelet spectrum of ocean waves and to synthesize sea surface elevations
      from vertical acceleration signals of a wave buoy through the continuous wavelet
      transform theory. The short-time wave features can be revealed by simultaneously
      examining the wavelet spectrum and the synthetic sea surface elevations. The in
      situ wave signals were applied to verify the practicality of the wavelet-based
      algorithm. We confirm that the spectral leakage and the noise at very-low
      frequency bins influenced the accuracies of the estimated wavelet spectrum and
      the synthetic sea surface elevations. The appropriate thresholds of these two
      factors were explored. To study the short-time wave features from the wave
      records, the acceleration signals recorded from an accelerometer inside a discus
      wave buoy are analysed. The results from the wavelet spectrum show the evidence
      of short-time nonlinear wave events. Our study also reveals that more surface
      profiles with higher vertical asymmetry can be found from short-time nonlinear
      wave with stronger harmonic spectral peak. Finally, we conclude that the
      algorithms of continuous wavelet transform are practical for revealing the short
      time wave features of the buoy acceleration signals. 

PMID- 23966189
TI  - A practical data recovery technique for long-term strain monitoring of mega
      columns during construction.
AB  - A practical data recovery method is proposed for the strain data lost during the
      safety monitoring of mega columns. The analytical relations among the measured
      strains are derived to recover the data lost due to unexpected errors in long
      term measurement during construction. The proposed technique is applied to
      recovery of axial strain data of a mega column in an irregular building structure
      during construction. The axial strain monitoring using the wireless strain
      sensing system was carried out for one year and five months between 23 July 2010
      and 22 February 2012. During the long-term strain sensing, three different types
      of measurement errors occurred. Using the recovery technique, the strain data
      that could not be measured at different intervals in the measurement were
      successfully recovered. It is confirmed that the problems that may occur during
      long-term wireless strain sensing of mega columns during construction could be
      resolved through the proposed recovery method. 

PMID- 23966190
TI  - Minimum detectable air velocity by thermal flow sensors.
AB  - Miniaturized thermal flow sensors have opened the doors for a large variety of
      new applications due to their small size, high sensitivity and low power
      consumption. Theoretically, very small detection limits of air velocity of some
      micrometers per second are achievable. However, the superimposed free convection
      is the main obstacle which prevents reaching these expected limits. Furthermore,
      experimental investigations are an additional challenge since it is difficult to
      generate very low flows. In this paper, we introduce a physical method, capable
      of generating very low flow values in the mixed convection region. Additionally,
      we present the sensor characteristic curves at the zero flow case and in the
      mixed convection region. Results show that the estimated minimum detectable air
      velocity by the presented method is 0.8 mm/s. The equivalent air velocity to the
      noise level of the sensor at the zero flow case is about 0.13 mm/s. 

PMID- 23966191
TI  - On the support of scientific workflows over Pub/Sub brokers.
AB  - The execution of scientific workflows is gaining importance as more computing
      resources are available in the form of grid environments. The Publish/Subscribe
      paradigm offers well-proven solutions for sustaining distributed scenarios while
      maintaining the high level of task decoupling required by scientific workflows.
      In this paper, we propose a new model for supporting scientific workflows that
      improves the dissemination of control events. The proposed solution is based on
      the mapping of workflow tasks to the underlying Pub/Sub event layer, and the
      definition of interfaces and procedures for execution on brokers. In this paper
      we also analyze the strengths and weaknesses of current solutions that are based
      on existing message exchange models for scientific workflows. Finally, we explain
      how our model improves the information dissemination, event filtering, task
      decoupling and the monitoring of scientific workflows. 

PMID- 23966192
TI  - Temperature-compensated clock skew adjustment.
AB  - This work analyzes several drift compensation mechanisms in wireless sensor
      networks (WSN). Temperature is an environmental factor that greatly affects
      oscillators shipped in every WSN mote. This behavior creates the need of
      improving drift compensation mechanisms in synchronization protocols. Using the
      Flooding Time Synchronization Protocol (FTSP), this work demonstrates that
      crystal oscillators are affected by temperature variations. Thus, the influence
      of temperature provokes a low performance of FTSP in changing conditions of
      temperature. This article proposes an innovative correction factor that minimizes
      the impact of temperature in the clock skew. By means of this factor, two new
      mechanisms are proposed in this paper: the Adjusted Temperature (AT) and the
      Advanced Adjusted Temperature (A2T). These mechanisms have been combined with
      FTSP to produce AT-FTSP and A2T-FTSP. Both have been tested in a network of
      TelosB motes running TinyOS. Results show that both AT-FTSP and A2T-FTSP improve
      the average synchronization errors compared to FTSP and other temperature
      compensated protocols (Environment-Aware Clock Skew Estimation and
      Synchronization for WSN (EACS) and Temperature Compensated Time Synchronization
      (TCTS)). 

PMID- 23966193
TI  - A comparative analysis between active and passive techniques for underwater 3D
      reconstruction of close-range objects.
AB  - In some application fields, such as underwater archaeology or marine biology,
      there is the need to collect three-dimensional, close-range data from objects
      that cannot be removed from their site. In particular, 3D imaging techniques are
      widely employed for close-range acquisitions in underwater environment. In this
      work we have compared in water two 3D imaging techniques based on active and
      passive approaches, respectively, and whole-field acquisition. The comparison is
      performed under poor visibility conditions, produced in the laboratory by
      suspending different quantities of clay in a water tank. For a fair comparison, a
      stereo configuration has been adopted for both the techniques, using the same
      setup, working distance, calibration, and objects. At the moment, the proposed
      setup is not suitable for real world applications, but it allowed us to conduct a
      preliminary analysis on the performances of the two techniques and to understand
      their capability to acquire 3D points in presence of turbidity. The performances
      have been evaluated in terms of accuracy and density of the acquired 3D points.
      Our results can be used as a reference for further comparisons in the analysis of
      other 3D techniques and algorithms. 

PMID- 23966194
TI  - Energy-efficient cognitive radio sensor networks: parametric and convex
      transformations.
AB  - Designing energy-efficient cognitive radio sensor networks is important to
      intelligently use battery energy and to maximize the sensor network life. In this
      paper, the problem of determining the power allocation that maximizes the energy
      efficiency of cognitive radio-based wireless sensor networks is formed as a
      constrained optimization problem, where the objective function is the ratio of
      network throughput and the network power. The proposed constrained optimization
      problem belongs to a class of nonlinear fractional programming problems. Charnes
      Cooper Transformation is used to transform the nonlinear fractional problem into
      an equivalent concave optimization problem. The structure of the power allocation
      policy for the transformed concave problem is found to be of a water-filling
      type. The problem is also transformed into a parametric form for which a epsilon
      optimal iterative solution exists. The convergence of the iterative algorithms is
      proven, and numerical solutions are presented. The iterative solutions are
      compared with the optimal solution obtained from the transformed concave problem,
      and the effects of different system parameters (interference threshold level, the
      number of primary users and secondary sensor nodes) on the performance of the
      proposed algorithms are investigated. 

PMID- 23966195
TI  - Measurement of phase difference for micromachined gyros driven by rotating
      aircraft.
AB  - This paper presents an approach for realizing a phase difference measurement of a
      new gyro. A silicon micromachined gyro was mounted on rotating aircraft for
      aircraft attitude control. Aircraft spin drives the silicon pendulum of a gyro
      rotating at a high speed so that it can sense the transverse angular velocity of
      the rotating aircraft based on the gyroscopic precession principle when the
      aircraft has transverse rotation. In applications of the rotating aircraft single
      channel control system, such as damping in the attitude stabilization loop, the
      gyro signal must be kept in sync with the control signal. Therefore, the phase
      difference between both signals needs to be measured accurately. Considering that
      phase difference is mainly produced by both the micromachined part and the signal
      conditioning circuit, a mathematical model has been established and analyzed to
      determine the gyro's phase frequency characteristics. On the basis of theoretical
      analysis, a dynamic simulation has been done for a case where the spin frequency
      is 15 Hz. Experimental results with the proposed measurement method applied to a
      silicon micromachined gyro driven by a rotating aircraft demonstrate that it is
      effective in practical applications. Measured curve and numerical analysis of
      phase frequency characteristic are in accordance, and the error between
      measurement and simulation is only 5.3%. 

PMID- 23966196
TI  - Modulated acquisition of spatial distortion maps.
AB  - This work discusses a novel approach to image acquisition which improves the
      robustness of captured data required for 3D range measurements. By applying a
      pseudo-random code modulation to sequential acquisition of projected patterns the
      impact of environmental factors such as ambient light and mutual interference is
      significantly reduced. The proposed concept has been proven with an experimental
      range sensor based on the laser triangulation principle. The proposed design can
      potentially enhance the use of this principle to a variety of outdoor
      applications, such as autonomous vehicles, pedestrians' safety, collision
      avoidance, and many other tasks, where robust real-time distance detection in
      real world environment is crucial. 

PMID- 23966197
TI  - An improved algorithm to generate a Wi-Fi fingerprint database for indoor
      positioning.
AB  - The major problem of Wi-Fi fingerprint-based positioning technology is the signal
      strength fingerprint database creation and maintenance. The significant temporal
      variation of received signal strength (RSS) is the main factor responsible for
      the positioning error. A probabilistic approach can be used, but the RSS
      distribution is required. The Gaussian distribution or an empirically-derived
      distribution (histogram) is typically used. However, these distributions are
      either not always correct or require a large amount of data for each reference
      point. Double peaks of the RSS distribution have been observed in experiments at
      some reference points. In this paper a new algorithm based on an improved double
      peak Gaussian distribution is proposed. Kurtosis testing is used to decide if
      this new distribution, or the normal Gaussian distribution, should be applied.
      Test results show that the proposed algorithm can significantly improve the
      positioning accuracy, as well as reduce the workload of the off-line data
      training phase. 

PMID- 23966198
TI  - Optical-based artificial palpation sensors for lesion characterization.
AB  - Palpation techniques are widely used in medical procedures to detect the presence
      of lumps or tumors in the soft breast tissues. Since these procedures are very
      subjective and depend on the skills of the physician, it is imperative to perform
      detailed a scientific study in order to develop more efficient medical sensors to
      measure and generate palpation parameters. In this research, we propose an
      optical-based, artificial palpation sensor for lesion characterization. This has
      been developed using a multilayer polydimethylsiloxane optical waveguide. Light
      was generated at the critical angle to reflect totally within the flexible and
      transparent waveguide. When a waveguide was compressed by an external force, its
      contact area would deform and cause the light to scatter. The scattered light was
      captured by a high-resolution camera and saved as an image format. To test the
      performance of the proposed system, we used a realistic tissue phantom with
      embedded hard inclusions. The experimental results show that the proposed sensor
      can detect inclusions and provide the relative value of size, depth, and Young's
      modulus of an inclusion. 

PMID- 23966199
TI  - Textile-based weft knitted strain sensors: effect of fabric parameters on sensor
      properties.
AB  - The design and development of textile-based strain sensors has been a focus of
      research and many investigators have studied this subject. This paper presents a
      new textile-based strain sensor design and shows the effect of base fabric
      parameters on its sensing properties. Sensing fabric could be used to measure
      articulations of the human body in the real environment. The strain sensing
      fabric was produced by using electronic flat-bed knitting technology; the base
      fabric was produced with elastomeric yarns in an interlock arrangement and a
      conductive yarn was embedded in this substrate to create a series of single loop
      structures. Experimental results show that there is a strong relationship between
      base fabric parameters and sensor properties. 

PMID- 23966200
TI  - Enhancing the simulation speed of sensor network applications by asynchronization
      of interrupt service routines.
AB  - Sensor network simulations require high fidelity and timing accuracy to be used
      as an implementation and evaluation tool. The cycle-accurate and instruction
      level simulator is the known solution for these purposes. However, this type of
      simulation incurs a high computation cost since it has to model not only the
      instruction level behavior but also the synchronization between multiple sensors
      for their causality. This paper presents a novel technique that exploits
      asynchronous simulations of interrupt service routines (ISR). We can avoid the
      synchronization overheads when the interrupt service routines are simulated
      without preemption. If the causality errors occur, we devise a rollback procedure
      to restore the original synchronized simulation. This concept can be extended to
      any instruction-level sensor network simulator. Evaluation results show our
      method can enhance the simulation speed up to 52% in the case of our experiments.
      For applications with longer interrupt service routines and smaller number of
      preemptions, the speedup becomes greater. In addition, our simulator is 2 to 11
      times faster than the well-known sensor network simulator. 

PMID- 23966201
TI  - National scale operational mapping of burnt areas as a tool for the better
      understanding of contemporary wildfire patterns and regimes.
AB  - This paper presents the results of an operational nationwide burnt area mapping
      service realized over Greece for the years 2007-2011, through the implementation
      of the so-called BSM_NOA dedicated method developed at the National Observatory
      of Athens for post-fire recovery management. The method exploits multispectral
      satellite imagery, such as Landsat-TM, SPOT, FORMOSAT-2, WorldView and IKONOS.
      The analysis of fire size distribution reveals that a high number of fire events
      evolve to large and extremely large wildfires under favorable wildfire
      conditions, confirming the reported trend of an increasing fire-severity in
      recent years. Furthermore, under such conditions wildfires affect to a higher
      degree areas at high altitudes, threatening the existence of ecologically
      significant ecosystems. Finally, recent socioeconomic changes and land
      abandonment has resulted in the encroachment of former agricultural areas of
      limited productivity by shrubs and trees, resulting both in increased fuel
      availability and continuity, and subsequently increased burnability. 

PMID- 23966202
TI  - Examining the association between oral health and oral HPV infection.
AB  - Oral human papillomavirus (HPV) infection is the cause of 40% to 80% of
      oropharyngeal cancers; yet, no published study has examined the role of oral
      health in oral HPV infection, either independently or in conjunction with other
      risk factors. This study examined the relation between oral health and oral HPV
      infection and the interactive effects of oral health, smoking, and oral sex on
      oral HPV infection. Our analyses comprised 3,439 participants ages 30 to 69 years
      for whom data on oral HPV and oral health were available from the nationally
      representative 2009-2010 National Health and Nutrition Examination Survey.
      Results showed that higher unadjusted prevalence of oral HPV infection was
      associated with four measures of oral health, including self-rated oral health as
      poor-to-fair [prevalence ratio (PR) = 1.56; 95% confidence interval (CI), 1.25
      1.95], indicated the possibility of gum disease (PR = 1.51; 95% CI, 1.13-2.01),
      reported use of mouthwash to treat dental problems in the past week (PR = 1.28;
      95% CI, 1.07-1.52), and higher number of teeth lost (Ptrend = 0.035). In
      multivariable logistic regression models, oral HPV infection had a statistically
      significant association with self-rated overall oral health (OR = 1.55; 95% CI,
      1.15-2.09), independent of smoking and oral sex. In conclusion, poor oral health
      was an independent risk factor of oral HPV infection, irrespective of smoking and
      oral sex practices. Public health interventions may aim to promote oral hygiene
      and oral health as an additional measure to prevent HPV-related oral cancers.

PMID- 23966203
TI  - Regulatory considerations for the potential development and application of metal
      cleanup values.
AB  - This article addresses the regulatory issues associated with the application of
      recent data to support Registration, Evaluation, Authorisation and Restriction of
      Chemical substances (REACH) requirements in Europe and the use of metal-specific
      parameters by other countries to generate remediation values for metals in soil.
      The purposes of this article are to: 1) present approaches and advances developed
      over the last decade in Europe for the REACH regulation and proposed in Australia
      by the National Environment Protection Council, 2) review current US and Canadian
      regulatory practices on ecological soil cleanup values, and 3) evaluate the
      application of new scientific approaches, methods, and soil criteria development
      processes used in other countries.

PMID- 23966204
TI  - GWAS of human bitter taste perception identifies new loci and reveals additional
      complexity of bitter taste genetics.
AB  - Human perception of bitterness displays pronounced interindividual variation.
      This phenotypic variation is mirrored by equally pronounced genetic variation in
      the family of bitter taste receptor genes. To better understand the effects of
      common genetic variations on human bitter taste perception, we conducted a genome
      wide association study on a discovery panel of 504 subjects and a validation
      panel of 104 subjects from the general population of Sao Paulo in Brazil.
      Correction for general taste-sensitivity allowed us to identify a SNP in the
      cluster of bitter taste receptors on chr12 (10.88- 11.24 Mb, build 36.1)
      significantly associated (best SNP: rs2708377, P = 5.31 * 10(-13), r(2) = 8.9%,
      beta = -0.12, s.e. = 0.016) with the perceived bitterness of caffeine. This
      association overlaps with-but is statistically distinct from-the previously
      identified SNP rs10772420 influencing the perception of quinine bitterness that
      falls in the same bitter taste cluster. We replicated this association to quinine
      perception (P = 4.97 * 10(-37), r(2) = 23.2%, beta = 0.25, s.e. = 0.020) and
      additionally found the effect of this genetic locus to be concentration specific
      with a strong impact on the perception of low, but no impact on the perception of
      high concentrations of quinine. Our study, thus, furthers our understanding of
      the complex genetic architecture of bitter taste perception. 

PMID- 23966205
TI  - DUX4 and DUX4 downstream target genes are expressed in fetal FSHD muscles.
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is one of the most prevalent adult
      muscular dystrophies. The common clinical signs usually appear during the second
      decade of life but when the first molecular dysregulations occur is still
      unknown. Our aim was to determine whether molecular dysregulations can be
      identified during FSHD fetal muscle development. We compared muscle biopsies
      derived from FSHD1 fetuses and the cells derived from some of these biopsies with
      biopsies and cells derived from control fetuses. We mainly focus on DUX4 isoform
      expression because the expression of DUX4 has been confirmed in both FSHD cells
      and biopsies by several laboratories. We measured DUX4 isoform expression by
      using qRT-PCR in fetal FSHD1 myotubes treated or not with an shRNA directed
      against DUX4 mRNA. We also analyzed DUX4 downstream target gene expression in
      myotubes and fetal or adult FSHD1 and control quadriceps biopsies. We show that
      both DUX4-FL isoforms are already expressed in FSHD1 myotubes. Interestingly,
      DUX4-FL expression level is much lower in trapezius than in quadriceps myotubes,
      which is confirmed by the level of expression of DUX4 downstream genes. We
      observed that TRIM43 and MBD3L2 are already overexpressed in FSHD1 fetal
      quadriceps biopsies, at similar levels to those observed in adult FSHD1
      quadriceps biopsies. These results indicate that molecular markers of the disease
      are already expressed during fetal life, thus opening a new field of
      investigation for mechanisms leading to FSHD. 

PMID- 23966206
TI  - Fluidic-directed assembly of aligned oligopeptides with pi-conjugated cores.
AB  - A microfluidic-based directed assembly strategy is employed to form highly
      aligned supramolecular structures. Formation of aligned synthetic oligopeptide
      nanostructures is accomplished using planar extensional flow, which induces
      alignment of underlying material suprastructures. Fluidic-directed assembly of
      supramolecular structures allows for unprecedented manipulation at the nano- and
      mesoscales, which has the potential to provide rapid and efficient control of
      functional material properties. 

PMID- 23966207
TI  - Lansoprazole for children with poorly controlled asthma.

PMID- 23966208
TI  - Smartphone-based optofluidic lab-on-a-chip for detecting pathogens from blood.
AB  - A novel smartphone-based detection device was created to detect infectious
      pathogens directly from diluted (10%) human whole blood. The model pathogen was
      histidine-rich protein 2 (HRP-2), an antigen specific to Plasmodium falciparum
      (malaria). Anti-HRP-2-conjugated submicrobeads were mixed with HRP-2-infused 10%
      blood in a lab-on-a-chip device. The white LED flash and the digital camera of
      the smartphone were used as light source and detector, which delivered light to
      and from the bead and blood mixture via optofluidic channels in the lab-on-a
      chip. The optofluidic channels were angled at 45 degrees to capture the Mie
      scatter from the sample. Considering the absorption and scattering
      characteristics of blood (red/infrared preferred) and the Mie scatter simulations
      for microbead immunoagglutination (UV preferred), blue detection showed the best
      results. The detection limit was 1 pg/mL in 10% blood. The linear range was from
      1 pg/mL to 10 ng/mL. A handheld device, easily attachable to a single smartphone,
      was finally designed and fabricated using optical mirrors and lenses and
      successfully detected the HRP-2 from 10% blood. The total assay time was
      approximately 10 min. The proposed device can potentially be used for detecting a
      wide range of blood infection with high sensitivity. 

PMID- 23966209
TI  - Restricting oral fluid and food intake during labour.
AB  - BACKGROUND: Restricting fluids and foods during labour is common practice across
      many birth settings with some women only being allowed sips of water or ice
      chips. Restriction of oral intake may be unpleasant for some women, and may
      adversely influence their experience of labour. OBJECTIVES: To determine the
      benefits and harms of oral fluid or food restriction during labour. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (30 June 2013) and reference lists of retrieved studies. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of restricting
      fluids and food for women in labour compared with women free to eat and drink.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the
      studies for inclusion, assessed risk of bias and carried out data extraction.
      MAIN RESULTS: We identified 19 studies of which we included five, involving 3130
      women. We excluded eight studies, one awaits classification and five are ongoing
      studies. All the included studies looked at women in active labour and at low
      risk of potentially requiring a general anaesthetic. One study looked at complete
      restriction versus giving women the freedom to eat and drink at will; two studies
      looked at water only versus giving women specific fluids and foods and two
      studies looked at water only versus giving women carbohydrate drinks.When
      comparing any restriction of fluids and food versus women given some nutrition in
      labour, the meta-analysis was dominated by one study undertaken in a highly
      medicalised environment. There were no statistically significant differences
      identified in: caesarean section (average risk ratio (RR) 0.89, 95% confidence
      interval (CI) 0.63 to 1.25, five studies, 3103 women), operative vaginal births
      (average RR 0.98, 95% CI 0.88 to 1.10, five studies, 3103 women) and Apgar scores
      less than seven at five minutes (average RR 1.43, 95% CI 0.77 to 2.68, four
      studies, 2902 infants), nor in any of the other outcomes assessed. Women's views
      were not assessed. The pooled data were insufficient to assess the incidence of
      Mendelson's syndrome, an extremely rare outcome. Other comparisons showed similar
      findings, except one study did report a significant increase in caesarean
      sections for women taking carbohydrate drinks in labour compared with water only,
      but these results should be interpreted with caution as the sample size was
      small. AUTHORS' CONCLUSIONS: Since the evidence shows no benefits or harms, there
      is no justification for the restriction of fluids and food in labour for women at
      low risk of complications. No studies looked specifically at women at increased
      risk of complications, hence there is no evidence to support restrictions in this
      group of women. Conflicting evidence on carbohydrate solutions means further
      studies are needed and it is critical in any future studies to assess women's
      views.

PMID- 23966210
TI  - Long-term depression of inhibitory synaptic transmission induced by spike-timing
      dependent plasticity requires coactivation of endocannabinoid and muscarinic
      receptors.
AB  - The precise timing of pre-postsynaptic activity is vital for the induction of
      long-term potentiation (LTP) or depression (LTD) at many central synapses. We
      show in synapses of rat CA1 pyramidal neurons in vitro that spike timing
      dependent plasticity (STDP) protocols that induce LTP at glutamatergic synapses
      can evoke LTD of inhibitory postsynaptic currents or STDP-iLTD. The STDP-iLTD
      requires a postsynaptic Ca(2+) increase, a release of endocannabinoids (eCBs),
      the activation of type-1 endocananabinoid receptors and presynaptic muscarinic
      receptors that mediate a decreased probability of GABA release. In contrast, the
      STDP-iLTD is independent of the activation of nicotinic receptors, GABAB Rs and G
      protein-coupled postsynaptic receptors at pyramidal neurons. We determine that
      the downregulation of presynaptic Cyclic adenosine monophosphate/protein Kinase A
      pathways is essential for the induction of STDP-iLTD. These results suggest a
      novel mechanism by which the activation of cholinergic neurons and retrograde
      signaling by eCBs can modulate the efficacy of GABAergic synaptic transmission in
      ways that may contribute to information processing and storage in the
      hippocampus.

PMID- 23966211
TI  - Multiple follicular papules on the back of an elderly man. Necrotizing
      infundibular crystalline folliculitis (NICF).

PMID- 23966212
TI  - Storing self-contained gel capillary cassettes for POC medical diagnostics.
AB  - For effective clinical uptake of the lab on a chip/point of care technology (LOC
      POC), in addition to cost advantages LOC-POC devices should offer multiple
      patient screening panels for related diseases as well as cold-chain
      transportation and storage abilities. We recently described a device that
      performs polymerase chain reaction (PCR) to simultaneously screen raw clinical
      samples from up to 16 patients for multiple infectious agents (Manage et al., Lab
      Chip, 2013, 13, 2576-2584). This cassette contains glass capillaries with
      desiccated semi-solid acrylamide gels that include all the reagents except for
      the sample, with integrated quality control. Here we report the development of
      protocols to store assembled PCR cassettes at room temperature, 4  degrees C or 
      20  degrees C as well as at +40  degrees C. We show that our cassettes are
      stable, with no loss of activity for at least 3 months at RT and at least 7
      months at 4  degrees C and -20  degrees C. However, the activity of desiccated
      cassettes degrades when stored for more than 2 weeks at 40  degrees C,
      insufficient time for post-manufacture delivery and use of cassette PCR. To
      address this, we have evaluated two stage storage protocols. PCR cassettes can
      initially be stored at 4  degrees C and -20  degrees C for prolonged periods of
      time and removed for shorter term storage at RT, retaining activity for at least
      a month, which would facilitate transport to remote areas for testing. Effective
      use of cassette PCR in high temperature regions of the world, for experimental
      purposes defined here as 40  degrees C, appears to be feasible only after a first
      stage storage in the cold, followed by no more than 1 week at 40  degrees C. This
      should allow sufficient time for delivery by the manufacturer to a central area
      well served by power and refrigeration, for later ambient temperature transport
      and use in under-resourced areas that lack refrigeration. 

PMID- 23966213
TI  - Early detection of COPD in general practice: implementation, workload and
      socioeconomic status. A mixed methods observational study.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is underdiagnosed in
      general practice. Our aim was to implement a population-based approach for the
      early detection of COPD and to assess its impact on primary care workload and
      costs, and the influence of socioeconomic status (SES). METHODS: An observational
      study with mixed methods was performed in 10 Dutch general practices of either
      low or moderate to high SES. The Respiratory Health Screening Questionnaire was
      posted during a three-month period to all persons aged 45, 55, and 65 years (one
      age group per month). The practices calculated the risk, and patients at high
      risk of COPD were invited for spirometry at the practice. The general
      practitioner used the spirometric results and a consultation to establish a
      clinical diagnosis. Qualitative and quantitative data on workload, cost, and
      barriers were evaluated. RESULTS: Ten practices returned 293 (35.3%) COPD risk
      tests for the three age groups. Participants from low SES practices responded
      better than those from moderate to high SES practices (40.8% vs. 30.5%). In
      practices with low SES 17.9% of the tests indicated high risk compared with 16.1%
      in practices with moderate to high SES. Nine patients (23%) were newly diagnosed
      with COPD. The healthcare providers' extra workload averaged 18.5 hours during
      the three months for one standard practice. The average cost of this survey
      programme (three age groups in three months) was ?520 for low SES practices and
      ?398 for moderate to high SES practices. All healthcare providers affirmed that
      the extra workload in this survey model is acceptable and feasible when finances
      are compensated. CONCLUSIONS: Early detection of COPD is feasible in daily life
      primary care. In moderate to high SES practices the costs of detecting COPD were
      less than in low SES practices.

PMID- 23966214
TI  - Early detection of COPD in general practice: patient or practice managed? A
      randomised controlled trial of two strategies in different socioeconomic
      environments.
AB  - BACKGROUND: The burden of chronic obstructive pulmonary disease (COPD) is high.
      Health benefits can be gained in primary care by early detection and preventive
      measures. AIMS: To compare the effectiveness of two strategies for population
      based early detection of COPD, taking into account different socioeconomic status
      (SES) settings. METHODS: Practices were randomised on strategy and stratified on
      SES setting. The Respiratory Health Screening Questionnaire (RHSQ) was
      distributed to all participants. In the practice-managed condition, the practice
      was responsible for the whole procedure, while in the patient-managed condition,
      patients were responsible for calculating their RHSQ risk score and applying for
      a spirometry test. The main outcome measure was the rate of COPD diagnoses after
      screening. RESULTS: More new COPD patients were detected in the practice-managed
      condition (36%) than in the patient-managed condition (18%). In low SES
      practices, more high-risk patients were found (16%) than in moderate-to-high SES
      practices (9%). Recalculated for a standard Dutch practice (2,350 patients), the
      yield would be 8.9 new COPD diagnoses, which is a 20% increase of known cases.
      CONCLUSIONS: The practice-managed variant of this screening procedure shows a
      substantial yield of new COPD diagnoses for both low and moderate-to-high SES
      practices.

PMID- 23966215
TI  - Long-term antibiotics in COPD: more benefit than harm?

PMID- 23966216
TI  - Every breath you take.

PMID- 23966217
TI  - Honey plus coffee versus systemic steroid in the treatment of persistent post
      infectious cough: a randomised controlled trial.
AB  - BACKGROUND: Persistent post-infectious cough (PPC) is a cough that remains after
      a common cold or an upper respiratory tract infection for more than three weeks
      or perhaps for many months. Two of the suggested treatments for PPC are systemic
      steroid and honey plus coffee. AIMS: The aim of this study was to evaluate and
      compare scientifically the therapeutic effects of these two regimens. METHODS: A
      double-blind randomised controlled trial was conducted from 2008 to 2011 at the
      Baqiyatallah University Hospital, Tehran, Iran. Included in the study were 97
      adults who had experienced PPC for more than three weeks. Patients with other
      causes of chronic cough, systemic disease, or abnormal routine laboratory tests
      were excluded. The participants were distributed into three groups. A jam like
      paste was prepared which consisted of honey plus coffee for the first group
      ('HC'), prednisolone for the second group (steroid, 'S'), and guaifenesin for the
      third group (control, 'C'). The participants were told to dissolve a specified
      amount of their product in warm water and to drink the solution every eight hours
      for one week. All the participants were evaluated before treatment and one week
      after completion of treatment to measure the severity of their cough. The main
      outcome measure was the mean cough frequency before and after one week's
      treatment calculated by a validated visual analogue cough questionnaire score.
      RESULTS: There were 97 adult patients (55 men) enrolled in this study with the
      mean of age of 40.1 years. The mean (+/- SD) cough scores pre- and post-treatment
      were: HC group 2.9 (0.3) pre-treatment and 0.2 (0.5) post-treatment (p < 0.001);
      steroid ('S') group 3.0 (0.0) pre-treatment and 2.4 (0.6) post-treatment (p <
      0.05); control ('C') group 2.8 (0.4) pre-treatment and 2.7 (0.5) post-treatment
      (p > 0.05). Analysis of variance showed a significant difference between the mean
      cough frequency before and after treatment in the HC group versus the S group (p<
      0.001). Honey plus coffee was found to be the most effective treatment modality
      for PPC. CONCLUSIONS: A combination of honey and coffee can be used as an
      alternative medicine in the treatment of PPC.

PMID- 23966218
TI  - The 51 kDa FADS3 is secreted in the ECM of hepatocytes and blood in rat.
AB  - The fatty acid desaturase (Fads) cluster is composed of three genes encoding for
      the Delta5- and Delta6-desaturases and FADS3. The two former proteins are
      involved in the fatty acid biosynthesis; the latter one shares a high sequence
      identity but has still no attributed function. In a previous work performed in
      rat, we described three isoforms of FADS3 expressed in a tissue-dependent manner.
      In the present study, we demonstrated a specific subcellular targeting depending
      on the isoform. In cultured hepatocytes, which mainly expressed the 51 kDa
      protein, FADS3 was unexpectedly present in the cytosolic fraction, but was also
      secreted in the extracellular matrix on fibronectin-containing fibers. The
      secretion pathway was investigated and we determined the presence of exosome-like
      vesicles on the FADS3-stained fibers. In parallel, FADS3 was detected in blood of
      hepatic vessel, and particularly in serum. In conclusion, this study demonstrated
      a very specific intra- and extracellular location of FADS3 in comparison with the
      Delta5- and Delta6-desaturases, suggesting a unique function for this putative
      desaturase, even if no activity has been yet identified neither in the
      extracellular matrix of hepatocytes nor in serum.

PMID- 23966219
TI  - What's causing toxicity in sediments? Results of 20 years of toxicity
      identification and evaluations.
AB  - Sediment toxicity identification and evaluation (TIE) methods have been used for
      20 yr to identify the causes of toxicity in sediments around the world. In the
      present study, the authors summarize and categorize results of 36 peer-reviewed
      TIE studies (67 sediments) into nonionic organic, cationic, ammonia, and "other"
      toxicant groups. Results are then further categorized according to whether the
      study was performed in freshwater or marine sediments and whether the study was
      performed using whole-sediment or interstitial-water TIE methods. When all
      studies were grouped, nonionic organic toxicants, either singly or in combination
      with other toxicants, were implicated in 70% of all studies. When studies were
      divided into interstitial-water TIE methodology compared with whole-sediment TIE
      methodology, results indicated that studies performed using interstitial-water
      TIE methods reported nonionic organic toxicity slightly more often than toxicity
      from cationic metals (67% compared with 49%). In contrast, studies using whole
      sediment TIE methods report nonionic organic chemical toxicity, either singly or
      in combination with another toxicant, in 90% of all sediments tested. Cationic
      metals play a much smaller role in whole-sediment TIE studies-fewer than 20% of
      all sediments had a metals signal. The discrepancy between the 2 methods can be
      attributed to exposure differences. Contrary to earlier findings, ammonia
      generally plays only a minor role in sediment toxicity.

PMID- 23966220
TI  - Photostimulation of whole-cell conductance in primary rat neocortical astrocytes
      mediated by organic semiconducting thin films.
AB  - Astroglial ion channels are fundamental molecular targets in the study of brain
      physiology and pathophysiology. Novel tools and devices intended for stimulation
      and control of astrocytes ion channel activity are therefore highly desirable.
      The study of the interactions between astrocytes and biomaterials is also
      essential to control and minimize reactive astrogliosis, in view of the
      development of implantable functional devices. Here, the growth of rat primary
      neocortical astrocytes on the top of a light sensitive, organic polymer film is
      reported; by means of patch-clamp analyses, the effect of the visible light
      stimulation on membrane conductance is then determined. Photoexcitation of the
      active material causes a significant depolarization of the astroglial resting
      membrane potential: the effect is associated to an increase in whole-cell
      conductance at negative potentials. The magnitude of the evoked inward current
      density is proportional to the illumination intensity. Biophysical and
      pharmacological characterization suggests that the ion channel mediating the
      photo-transduction mechanism is a chloride channel, the ClC-2 channel. These
      results open interesting perspectives for the selective manipulation of astrocyte
      bioelectrical activity by non-invasive, label-free, organic-based,
      photostimulation approaches. 

PMID- 23966221
TI  - Molecular dynamics simulations reveal that apo-HisJ can sample a closed
      conformation.
AB  - The Escherichia coli histidine binding protein HisJ is a type II periplasmic
      binding protein (PBP) that preferentially binds histidine and interacts with its
      cytoplasmic membrane ABC transporter, HisQMP2 , to initiate histidine transport.
      HisJ is a bilobal protein where the larger Domain 1 is connected to the smaller
      Domain 2 via two linking strands. Type II PBPs are thought to undergo "Venus
      flytrap" movements where the protein is able to reversibly transition from an
      open to a closed conformation. To explore the accessibility of the closed
      conformation to the apo state of the protein, we performed a set of all-atom
      molecular dynamics simulations of HisJ starting from four different
      conformations: apo-open, apo-closed, apo-semiopen, and holo-closed. The
      simulations reveal that the closed conformation is less dynamic than the open
      one. HisJ experienced closing motions and explored semiopen conformations that
      reverted to closed forms resembling those found in the holo-closed state.
      Essential dynamics analysis of the simulations identified domain closing/opening
      and twisting as main motions. The formation of specific inter-hinge strand and
      interdomain polar interactions contributed to the adoption of the closed apo
      conformations although they are up to 2.5-fold less prevalent compared with the
      holo-closed simulations. The overall sampling of the closed form by apo-HisJ
      provides a rationale for the binding of unliganded PBPs with their cytoplasmic
      membrane ABC transporters.

PMID- 23966222
TI  - The European medicines agency review of abiraterone for the treatment of
      metastatic castration-resistant prostate cancer in adult men after docetaxel
      chemotherapy and in chemotherapy-naive disease: summary of the scientific
      assessment of the committee for medicinal products for human use.
AB  - On September 5, 2011, abiraterone was approved in the European Union in
      combination with prednisone or prednisolone for the treatment of metastatic
      castration-resistant prostate cancer (CRPC) in adult men whose disease has
      progressed on or after a docetaxel-based chemotherapy regimen. On December 18,
      2012, the therapeutic indication was extended to include the use of abiraterone
      in combination with prednisone or prednisolone for the treatment of metastatic
      CRPC in adult men who are asymptomatic or mildly symptomatic after failure of
      androgen deprivation therapy in whom chemotherapy is not yet clinically
      indicated. Abiraterone is a selective, irreversible inhibitor of cytochrome P450
      17alpha, an enzyme that is key in the production of androgens. Inhibition of
      androgen biosynthesis deprives prostate cancer cells from important signals for
      growth, even in cases of resistance to castration. At the time of European Union
      approval and in a phase III trial in CRPC patients who had failed at least one
      docetaxel-based chemotherapy regimen, median overall survival for patients
      treated with abiraterone was 14.8 months versus 10.9 months for those receiving
      placebo (hazard ratio, 0.65; 95% confidence interval 0.54-0.77; p < .0001). In a
      subsequent phase III trial in a similar but chemotherapy-naive patient
      population, median radiographic progression-free survival was 16.5 months for
      patients in the abiraterone treatment arm versus 8.3 months for patients in the
      placebo arm (hazard ratio, 0.53; 95% confidence interval, 0.45-0.62; p < .0001).
      Abiraterone was most commonly associated with adverse reactions resulting from
      increased or excessive mineralocorticoid activity. These were generally
      manageable with basic medical interventions. The most common side effects
      (affecting more than 10% of patients) were urinary tract infection, hypokalemia,
      hypertension, and peripheral edema. 

PMID- 23966223
TI  - The systemic inflammatory response and its relationship to pain and other
      symptoms in advanced cancer.
AB  - INTRODUCTION: Inflammation has been identified as a hallmark of cancer and may be
      necessary for tumorgenesis and maintenance of the cancer state. Inflammation
      related symptoms are common in those with cancer; however, little is known about
      the relationship between symptoms and systemic inflammation in cancer. The aim of
      the present study was to examine the relationship between symptoms and systemic
      inflammation in a large cohort of patients with advanced cancer. METHODS: Data
      from an international cohort of patients with advanced cancer were analyzed.
      Symptoms and patient-related outcomes were recorded using the European
      Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-
      Core Questionnaire. Systemic inflammation was assessed using C-reactive protein
      levels. The relationship between these symptoms and systemic inflammation was
      examined using Spearman rank correlation (rho) and the Mann-Whitney U test.
      RESULTS: Data were available for 1,466 patients across eight European countries;
      1,215 patients (83%) had metastatic disease at study entry. The median survival
      was 3.8 months (interquartile range [IQR] 1.3-12.2 months). The following were
      associated with increased levels of inflammation: performance status (rho =
      .179), survival (rho = .347), pain (rho = .154), anorexia (rho = .206), cognitive
      dysfunction (rho = .137), dyspnea (p= .150), fatigue (rho = .197), physical
      dysfunction (rho = .207), role dysfunction (rho = .176), social dysfunction (rho
      = .132), and poor quality of life (rho = .178). All were statistically
      significant at p < .001. CONCLUSION: The results show that the majority of cancer
      symptoms are associated with inflammation. The strength of the potential
      relationship between systemic inflammation and common cancer symptoms should be
      examined further within the context of an anti-inflammatory intervention trial.

PMID- 23966224
TI  - Adjuvant treatment for gastric cancer: chemotherapy versus radiation.
AB  - Gastric cancer is among the leading causes of cancer death worldwide. Surgery is
      the only curative modality, but mortality remains high because a significant
      number of patients have recurrence after complete surgical resection.
      Chemotherapy, radiation, and chemoradiotherapy have all been studied in an
      attempt to reduce the risk for relapse and improve survival. There is no globally
      accepted standard of care for resectable gastric cancer, and treatment strategies
      vary across the world. Postoperative chemoradiation with 5
      fluorouracil/leucovorin is most commonly practiced in the United States; however,
      recent clinical trials from Asia have shown benefit of adjuvant chemotherapy
      alone and have questioned the role of radiation. In this review, we examine the
      current literature on adjuvant treatment of gastric cancer and discuss the roles
      of radiation and chemotherapy, particularly in light of these new data and their
      applicability to the Western population. We highlight some of the ongoing and
      planned clinical trials in resectable gastric cancer and identify future
      directions as well as areas where further research is needed. 

PMID- 23966225
TI  - Tuning the bandgap of exfoliated InSe nanosheets by quantum confinement.
AB  - Strong quantization effects and tuneable near-infrared photoluminescence emission
      are reported in mechanically exfoliated crystals of gamma-rhombohedral
      semiconducting InSe. The optical properties of InSe nanosheets differ
      qualitatively from those reported recently for exfoliated transition metal
      dichalcogenides and indicate a crossover from a direct to an indirect band gap
      semiconductor when the InSe flake thickness is reduced to a few nanometers. 

PMID- 23966226
TI  - Mitigating fluorescence spectral overlap in wide-field endoscopic imaging.
AB  - The number of molecular species suitable for multispectral fluorescence imaging
      is limited due to the overlap of the emission spectra of indicator fluorophores,
      e.g., dyes and nanoparticles. To remove fluorophore emission cross-talk in wide
      field multispectral fluorescence molecular imaging, we evaluate three different
      solutions: (1) image stitching, (2) concurrent imaging with cross-talk ratio
      subtraction algorithm, and (3) frame-sequential imaging. A phantom with
      fluorophore emission cross-talk is fabricated, and a 1.2-mm ultrathin scanning
      fiber endoscope (SFE) is used to test and compare these approaches. Results show
      that fluorophore emission cross-talk could be successfully avoided or
      significantly reduced. Near term, the concurrent imaging method of wide-field
      multispectral fluorescence SFE is viable for early stage cancer detection and
      localization in vivo. Furthermore, a means to enhance exogenous fluorescence
      target-to-background ratio by the reduction of tissue autofluorescence background
      is demonstrated.

PMID- 23966227
TI  - Neonatal opiate withdrawal and rooming-in: a retrospective analysis of a single
      center experience.
AB  - AIM: To evaluate our treatment of neonatal abstinence syndrome (NAS), our
      experience with rooming-in of opiate-dependent mothers and to examine the
      influence of rooming-in on short term outcome of infants exposed to opiates in
      utero. METHOD: Retrospective analysis of maternal and perinatal data of newborn
      infants with NAS treated between 2004 and 2011 in a level 3 academic children's
      hospital in a German metropolis. Therapy of NAS and duration of therapy, length
      of hospital stay and costs were considered in particular. FINDINGS: Data of 77
      newborns with NAS were analysed. 84.6% of infants were treated with tincture of
      opium (79.2% rooming-in, 88.7% no rooming-in). Infants with rooming-in (n=24) had
      a 17% shorter median duration of therapy [27.0 d (IQR 24.0-38.5), no rooming-in
      (n=53) 32.5 d (IQR 25.0-54.5)] and shorter median length of hospital stay [33.0 d
      (IQR 28.0-48.0), no rooming-in 41.5 d (IQR 30.3-54.5)]. Demographic data was
      comparable between newborns and mothers with or without rooming-in. Costs were
      median 13 457 ? (IQR 8 967-17 494)/patient [rooming-in: 9 547 ? (IQR 7 024-16
      135), no rooming-in: 14 486 ? (IQR 9 479-19 352)]. CONCLUSIONS: Rooming-in in NAS
      should be encouraged to shorten duration of therapy and length of hospital stay
      and thereby reduce costs. No major problems arose in the care of the infants with
      NAS when parents stayed with their infants but close monitoring of the newborn
      and strict instruction of parents are required.

PMID- 23966228
TI  - Physical activity and sedentary time: male perceptions in a university work
      environment.
AB  - Promoting physical activity and reducing sedentary time in males can be
      challenging, and interventions tailored specifically for males are limited.
      Understanding male perceptions of physical activity and sedentary behavior is
      important to inform development of relevant interventions, especially for males
      working in an office setting. As part of a larger intervention study to increase
      physical activity and reduce sedentary time, male university employees aged 35 to
      64 years were invited to partake in focus groups to discuss benefits, motivators,
      and barriers related to physical activity and sedentary time. Five semistructured
      focus group sessions, ranging from 50 to 70 minutes in duration, were conducted
      on two campuses at an Australian university. A total of 15 participants (9
      academic/faculty staff and 6 professional staff), with a mean (+/- SD) age of
      46.1 (+/-8.0) years took part in the study. Health and family were commonly
      discussed motivators for physical activity, whereas time constraints and work
      commitments were major barriers to physical activity participation. Sedentary
      time was a perceived "by-product" of participants' university employment, as a
      substantial proportion of their days were spent sitting, primarily at a computer.
      Participants believed that physical activity should be recognized as a legitimate
      activity at work, embedded within the university culture and endorsed using a top
      down approach. It is important to encourage breaks in sedentary time and
      recognize physical activity as a legitimate health-promoting activity that is
      supported and encouraged during working hours. These findings can be used as a
      platform from which to develop targeted strategies to promote physical activity
      in male university employees. 

PMID- 23966229
TI  - Alginate lyase and ciprofloxacin co-immobilization on biopolymeric microspheres
      for cystic fibrosis treatment.
AB  - A new formulation is described based on biopolymeric microspheres containing
      alginate lyase (AL) and ciprofloxacin (Cip) for sustainable oral delivery in CF
      patients. Alginate (ALG) and high-methoxyl pectin (HMP) are selected as the
      biopolymers to develop a composite matrix. ALG microspheres coated with HMP and
      ALG-HMP blend are gelled in water/organic solvents mixtures, obtaining Cip
      encapsulations from 46.0 to 100.0%. ALG-HMP shows a Cip sustainable release
      profile and is able to encapsulate 90.0% of AL, showing 76.0% enzyme activity
      after release under simulated intestinal conditions. The developed system is a
      promising delivery carrier to treat chronic infection of Pseudomonas aeruginosa
      and to reduce the viscoelasticity of the mucus accumulated into intestine of CF
      patients. 

PMID- 23966230
TI  - In situ laser micropatterning of proteins for dynamically arranging living cells.
AB  - This study shows the modification of the surface of polymer-layered glass
      substrates to form biofunctional micropatterns through femtosecond laser ablation
      in an aqueous solution. Domains of micrometer size on a substrate can be
      selectively converted from proteinphobic (resistant to protein adsorption) to
      proteinphilic, allowing patterning of protein features under physiological
      aqueous conditions. When femtosecond laser pulses (800 nm, 1 kHz, 200-500 nJ per
      pulse) were focused on and scanned on the substrate, which was glass covered with
      the proteinphobic polymer 2-methacryloyloxyethylphosphorylcholine (MPC), the
      surface became proteinphilic. Surface analysis by X-ray photoelectron
      spectroscopy (XPS) and scanning electron microscopy (SEM) reveals that the laser
      ablates the MPC polymer. Extracellular matrix (ECM) proteins were bound to the
      laser-ablated surface by physisorption. Since femtosecond laser ablation is
      induced under physiological aqueous conditions, this approach can form
      micropatterns of functional ECM proteins with minimal damage. This method was
      applied to pattern collagen, laminin, and gelatin on the substrate. Removal of an
      ECM protein from the substrate followed by replacement with another ECM protein
      was achieved on demand at a specific location and time by the same laser ablation
      method. Living cells adhered to the fabricated domains where ECM proteins were
      arranged. The modification of patterning during cell culture was used to control
      cell migration and form arrays of different cells. 

PMID- 23966231
TI  - Reducing greenhouse gas emissions and adapting agricultural management for
      climate change in developing countries: providing the basis for action.
AB  - Agriculture in developing countries has attracted increasing attention in
      international negotiations within the United Nations Framework Convention on
      Climate Change for both adaptation to climate change and greenhouse gas
      mitigation. However, there is limited understanding about potential
      complementarity between management practices that promote adaptation and
      mitigation, and limited basis to account for greenhouse gas emission reductions
      in this sector. The good news is that the global research community could provide
      the support needed to address these issues through further research linking
      adaptation and mitigation. In addition, a small shift in strategy by the
      Intergovernmental Panel on Climate Change (IPCC) and ongoing assistance from
      agricultural organizations could produce a framework to move the research and
      development from concept to reality. In turn, significant progress is possible in
      the near term providing the basis for UNFCCC negotiations to move beyond
      discussion to action for the agricultural sector in developing countries. 

PMID- 23966232
TI  - Evaluating the sorption of organophosphate esters to different sourced humic
      acids and its effects on the toxicity to Daphnia magna.
AB  - Because of large usage as flame retardants and additives, organophosphate esters
      (OPEs) are widely detected in the environment and regarded as emerging
      contaminants. However, the sorption of OPEs to organic matter and its effects
      have scarcely been studied. In the present study, the sorption of 9 commonly used
      OPEs to 4 representative humic acids--Elliott Soil humic acid, Suwannee River
      humic acid, Aldrich humic acid, and Acros humic acid--in the range of 0 mg/L to
      50 mg/L dissolved organic carbon (DOC), was evaluated with negligible-depletion
      solid-phase microextraction and verified by its impacts on the toxicity to the
      aquatic invertebrate Daphnia magna. Whereas OPEs with a high octanol/water
      partition coefficient (log K(OW)=4.51-6.64) were associated with humic acids
      mainly by hydrophobic interaction with DOC partition coefficient (K(DOC)) in the
      range of 102.22 to 105.31, the sorption of low-K(OW) OPEs (log K(OW)=-0.65 to
      2.59) to humic acids was not hydrophobic interaction-dominant, with K(DOC) in the
      range of 103.47 to 104.29. These results were corroborated by the effects of
      humic acids on the acute toxicity of 3 high-K(OW) OPEs to D. magna. The sorption
      of OPEs to Suwannee River humic acid was weak and had negligible effects on the
      toxicity of high-K(OW) OPEs; the presence of terrestrial Acros humic acid (50
      mg/L DOC), however, significantly decreased the toxicity by 53% to 60%. The
      results indicated that the strong sorption between high-K(OW) OPEs and
      terrestrial humic acid might affect their transportation and bioavailability.

PMID- 23966233
TI  - Putting molecules in their place.
AB  - Each class of microscope is limited to imaging specific aspects of cell structure
      and/or molecular organization. However, imaging the specimen by complementary
      microscopes and correlating the data can overcome this limitation. Whilst not a
      new approach, the field of correlative imaging is currently benefitting from the
      emergence of new microscope techniques. Here we describe the correlation of
      cryogenic fluorescence tomography (CFT) with soft X-ray tomography (SXT). This
      amalgamation of techniques integrates 3D molecular localization data (CFT) with a
      high-resolution, 3D cell reconstruction of the cell (SXT). Cells are imaged in
      both modalities in a near-native, cryopreserved state. Here we describe the
      current state of the art in correlative CFT-SXT, and discuss the future outlook
      for this method.

PMID- 23966234
TI  - Damage control: a balancing act.

PMID- 23966235
TI  - Protein structure modeling for CASP10 by multiple layers of global optimization.
AB  - In the template-based modeling (TBM) category of CASP10 experiment, we introduced
      a new protocol called protein modeling system (PMS) to generate accurate protein
      structures in terms of side-chains as well as backbone trace. In the new
      protocol, a global optimization algorithm, called conformational space annealing
      (CSA), is applied to the three layers of TBM procedure: multiple sequence
      structure alignment, 3D chain building, and side-chain re-modeling. For 3D chain
      building, we developed a new energy function which includes new distance
      restraint terms of Lorentzian type (derived from multiple templates), and new
      energy terms that combine (physical) energy terms such as dynamic fragment
      assembly (DFA) energy, DFIRE statistical potential energy, hydrogen bonding term,
      etc. These physical energy terms are expected to guide the structure modeling
      especially for loop regions where no template structures are available. In
      addition, we developed a new quality assessment method based on random forest
      machine learning algorithm to screen templates, multiple alignments, and final
      models. For TBM targets of CASP10, we find that, due to the combination of three
      stages of CSA global optimizations and quality assessment, the modeling accuracy
      of PMS improves at each additional stage of the protocol. It is especially
      noteworthy that the side-chains of the final PMS models are far more accurate
      than the models in the intermediate steps.

PMID- 23966236
TI  - Transport of nitric oxide by perfluorocarbon emulsion.
AB  - Perfluorocarbon (PFC) emulsions can transport and release various gases based on
      concentration gradients. The objective of this study was to determine the
      possibility of carrying and delivering exogenous nitric oxide (NO) into the
      circulation by simply loading PFC emulsion with NO prior infusion. PFC was
      equilibrated with room air (PFC) or 300 ppm NO (PFC-NO) at atmospheric pressure.
      Isotonic saline solution was used as a volume control (Saline). PFC and PFC-NO
      were infused at a dose of 3.5 mL/kg in the hamster window chamber model. Blood
      chemistry, and systemic and microvascular hemodynamic response were measured.
      Infusion of PFC preloaded with NO reduced blood pressure, induced microvascular
      vasodilation and increased capillary perfusion; although these changes lasted
      less than 30 min post infusion. On the other hand, infusion of PFC (without NO)
      produced vasoconstriction; however, the vasoconstriction was followed by
      vasodilatation at 30 min post infusion. Plasma nitrite and nitrate increased 15
      min after infusion of NO preloaded PFC compared with PFC, 60 min after infusion
      nitrite and nitrate were not different, and 90 min after infusion plasma S
      nitrosothiols increased in both groups. Infusion of NO preloaded PFC resulted in
      acute vascular relaxation, where as infusion of PFC (without NO) produced
      vasoconstriction, potentially due to NO sequestration by the PFC micelles. The
      late effects of PFC infusion are due to NO redistribution and plasma S
      nitrosothiols. Gas solubility in PFC can provide a tool to modulate plasma
      vasoactive NO forms availability and improve microcirculatory function and
      promote increased blood flow.

PMID- 23966237
TI  - Interactions between pregnancy, obstructive sleep apnea, and gestational diabetes
      mellitus.
AB  - CONTEXT: Questionnaire studies linked symptoms of obstructive sleep apnea (OSA)
      to the risk of gestational diabetes mellitus (GDM). Whether this association is
      present when OSA is assessed objectively by polysomnography is not known.
      OBJECTIVE: The objective of the study was to assess the relationship between
      pregnancy, OSA, and GDM. DESIGN, SETTING, AND PARTICIPANTS: We conducted
      observational case-control studies using polysomnography in 15 nonpregnant,
      nondiabetic women (NP-NGT), 15 pregnant women with normal glucose tolerance (P
      NGT), and 15 pregnant women with GDM (P-GDM). The groups were frequency matched
      for age and race/ethnicity. Pregnant women were studied during the late second to
      early third trimester. MAIN OUTCOME MEASURES: Comparisons of OSA diagnosis and
      sleep parameters between NP-NGT and P-NGT to assess the impact of pregnancy and
      between P-NGT and P-GDM to explore the association between GDM and OSA were
      measured. RESULTS: Compared with NP-NGT, P-NGT women had a higher apnea hypopnea
      index (AHI) (median 2.0 vs 0.5, P = .03) and more disrupted sleep as reflected by
      a higher wake time after sleep onset (median 66 vs 21 min, P < .01) and a higher
      microarousal index (median 16.4 vs 10.6, P = .01). Among the pregnant women, P
      GDM had markedly lower total sleep time (median 397 vs 464 min, P = .02) and a
      higher AHI (median 8.2 vs 2.0, P = .05) than P-NGT women. OSA was more prevalent
      in P-GDM than in P-NGT women (73% vs 27%, P = .01). After adjustment for
      prepregnancy body mass index, the diagnosis of GDM was associated with a
      diagnosis of OSA [odds ratio 6.60 (95% confidence interval 1.15-37.96)]. In
      pregnancy, after adjusting for prepregnancy body mass index, higher microarousal
      index significantly associated with higher hemoglobin A1c and fasting glucose
      levels. Higher oxygen desaturation index was associated with higher fasting
      glucose levels. CONCLUSION: Pregnancy is associated with sleep disturbances.
      Sleep is more disturbed in GDM than in P-NGT women. There is a strong association
      between GDM and OSA.

PMID- 23966238
TI  - The impact of insulin-independent, glucagon-induced suppression of total ghrelin
      on satiety in obesity and type 1 diabetes mellitus.
AB  - AIMS/HYPOTHESIS: The mechanisms underlying glucagon-induced satiety are
      incompletely understood. The glucagon-induced reduction in total ghrelin exerted
      at the hypothalamo-pituitary level might be responsible for this effect. Here we
      investigated glucagon-suppressive effects on circulating total and acyl-ghrelin,
      both in obesity and in type 1 diabetes mellitus (T1DM), with respect to the role
      of glucagon in appetite control. We further aimed to identify a possible
      mechanistic impact of changes in endogenous insulin. METHODS: In our prospective,
      double-blinded, placebo-controlled study, we investigated the endocrine and
      metabolic responses to intramuscular glucagon administration in 13 patients with
      T1DM (6 males, 7 females; body mass index [BMI] 24.8 +/- 0.95 kg/m(2)), 11 obese
      participants (OP; 5 males, 6 females; BMI 34.4 +/- 1.7 kg/m(2)), and 13 healthy
      lean participants (LP; 6 males, 7 females; BMI 21.7 +/- 0.6 kg/m(2)). RESULTS: As
      compared with placebo, glucagon significantly increased satiety index in T1DM and
      in LP (P < .001) but failed to induce satiety in OP (P = .152). Total ghrelin
      significantly decreased after glucagon administration in all study groups (P <
      .01). Similarly, acyl-ghrelin significantly decreased in LP (P < .01). However,
      acyl-ghrelin concentrations showed no change in OP (P = .248) and even increased
      substantially in T1DM (P < .01). Changes in acyl-ghrelin correlated positively
      with changes in nonesterified fatty acid concentrations in all groups (r = 0.31
      0.43; P < .01). CONCLUSIONS/INTERPRETATION: Glucagon-induced satiety was
      preserved in T1DM but not in obesity. This effect was unrelated to changes in
      total or acylated ghrelin and was independent of endogenous insulin release. In
      contrast to the insulin-independent glucagon-induced suppression of total
      ghrelin, glucagon- and/or insulin-induced modification of lipolysis may determine
      changes in acylated ghrelin.

PMID- 23966239
TI  - Vitamin D, muscle function, and falls in older adults: does reduced deposition of
      intramuscular adipose tissue influence the relationship?

PMID- 23966241
TI  - Loss-of-function and gain-of-function mutations of calcium-sensing receptor:
      functional analysis and the effect of allosteric modulators NPS R-568 and NPS
      2143.
AB  - OBJECTIVE: Activating mutations in the calcium-sensing receptor (CASR) gene cause
      autosomal dominant hypoparathyroidism, and heterozygous inactivating CASR
      mutations cause familial hypocalciuric hypercalcemia. Recently, there has been a
      focus on the use of allosteric modulators to restore the functional activity of
      mutant CASRs. In this study, the effect of allosteric modulators NPS R-568 and
      NPS 2143 on CASR mutants was studied in vitro. METHODS: DNA sequence analysis of
      the CASR gene was undertaken in autosomal dominant hypoparathyroidism and
      familial hypocalciuric hypercalcemia Japanese patients, and the functional
      consequences for the Gi-MAPK pathway and cell surface expression of CASR were
      determined. Furthermore, we studied the effect of NPS R-568 and NPS 2143 on the
      signal transduction activity and cell surface expression of each mutant CASR.
      RESULTS: We identified 3 activating mutations (S122C, P569H, and I839T) and 2
      inactivating mutations (A110T and R172G) in patients. The activating and
      inactivating mutations caused leftward and rightward shifts, respectively, in the
      dose-response curves of the signaling pathway. NPS R-568 rescued the signal
      transduction capacity of 2 inactivating mutants without increasing cell surface
      expression levels. NPS 2143 suppressed the enhanced activity of the activating
      mutants without altering cell surface expression levels, although A843E, which is
      a constitutively active mutant, was suppressed to a lesser degree. CONCLUSIONS:
      We have identified 4 novel mutations of CASR. Moreover, our results indicate that
      allosteric modulators can restore the activity of the loss- and gain-of-function
      mutant CASRs, identified in this study.

PMID- 23966240
TI  - A cross-sectional association between bone mineral density and parathyroid
      hormone and other biomarkers in community-dwelling young adults: the CARDIA
      study.
AB  - CONTEXT: Most association studies of bone-related biomarkers (BBMs) with bone
      mineral density (BMD) have been conducted in postmenopausal women. OBJECTIVE: We
      tested whether the following BBMs were cross-sectionally associated with BMD
      among young adults: serum 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin
      D (25OHD), PTH, osteocalcin, bone-specific alkaline phosphatase (BAP), and
      urinary pyridinoline/urinary creatinine. SETTING AND PARTICIPANTS: We studied 319
      individuals (134 women, 149 black, 24-36 years) recruited during 1992 through
      1993 in Oakland, California. BMD was assessed with dual-energy x-ray
      absorptiometry. Linear regression models estimated the association between BMD
      and each BBM. RESULTS: 1,25(OH)2D was inversely associated with all BMDs. 25OHD
      was positively, and PTH inversely, associated with lumbar spine, total hip, and
      whole-body BMD. BAP was inversely associated with left arm, right arm, and whole
      body BMD but not with spine or hip BMD. Neither osteocalcin nor urinary
      pyridinoline/urinary creatinine was associated with BMD. When we placed all BBMs
      (including 1,25(OH)2D) in one model, the pattern and magnitude of association was
      similar except for PTH, which was attenuated. The association of BMD and BBMs did
      not differ significantly by race or sex. CONCLUSIONS: In this cross-sectional
      study of healthy young men and women who had PTH levels considered normal in
      clinical practice, higher PTH was associated with lower BMD, particularly in
      weight-bearing sites (ie, spine and hip). The inverse association of 1,25(OH)2D,
      together with the attenuation of PTH, suggests that the observed association of
      PTH is mediated by 1,25(OH)2D. BAP was inversely associated with arm BMD. BBMs
      can be important markers of skeletal activity in young adults, but their clinical
      role on bone health among this population is yet to be fully determined.

PMID- 23966242
TI  - Effects of ACE I/D polymorphism and aerobic training on the immune-endocrine
      network and cardiovascular parameters of postmenopausal women.
AB  - CONTEXT: Estrogen deficiency, systemic low-grade inflammation, and reduction of
      adrenal gland function have central roles in noncommunicable chronic disease
      (NCD) development. With angiotensin-converting enzyme (ACE) insertion/deletion
      (I/D) polymorphism, the deletion variant (DD) is related to higher levels of
      circulating angiotensin II than I allele carriers (II/ID), which might interact
      with all of these molecular pathways to increase NCDs risk. On the other hand,
      physical exercise counteracts the occurrence of NCDs, potentially acting on the
      same pathways. OBJECTIVES: The aim of the study was to investigate the effects of
      walking training on adrenal steroid and cytokine levels and on cardiovascular
      parameters in postmenopausal women with ACE I/D genotypes. METHODS: Thirty-six
      (DD = 15, II/ID = 21) sedentary postmenopausal women (mean age, 56 +/- 4 y)
      participated in a 13-week program of walking training at moderate intensity.
      Heart rate, blood pressure, double product, TNF-alpha, dehydroepiandrosterone
      sulfate (DHEA-S), and cortisol were evaluated before and after the intervention
      program. RESULTS: Before walking training, the ACE DD genotype showed
      significantly higher TNF-alpha (P = .007) and lower DHEA-S concentrations (P =
      .022) than the ACE II/ID individuals. After walking training, both subgroups
      significantly decreased TNF-alpha plasma levels and cortisol/DHEA-S ratio (P =
      .001 and P = .016, respectively) and significantly increased DHEA-S levels (P <
      .001). Moreover, all the cardiovascular parameters were significantly reduced in
      the ACE DD participants (P <= .05), whereas the ACE I-allele carriers showed a
      decrease in heart rate (P <= .05) and the double product (P <= .05). CONCLUSION:
      ACE I/D polymorphism is linked to different adrenal steroid and cytokine levels,
      and ACE I-allele carriers show a better adrenal activity and systemic
      inflammatory profile. The introduction of walking training positively influences
      the menopause immune-neuroendocrine changes, independent of ACE I/D genotype.

PMID- 23966243
TI  - Regional variation in thyroid cancer incidence in Belgium is associated with
      variation in thyroid imaging and thyroid disease management.
AB  - CONTEXT: Increased thyroid cancer incidence is at least partially attributed to
      increased detection and shows considerable regional variation. OBJECTIVE: We
      investigated whether regional variation in cancer incidence was associated with
      variations in thyroid disease management. DESIGN: We conducted a retrospective
      population-based cohort study that involved linking data from the Belgian Health
      Insurance database and the Belgian Cancer Registry to compare thyroid-related
      procedures between regions with high and low cancer incidence. MAIN OUTCOME
      MEASURES: Primary outcome measures were rates of TSH testing, imaging, fine
      needle aspiration cytology (FNAC), and thyroid surgery. Secondary study outcomes
      were proportions of subjects with thyrotoxicosis and nodular disease treated with
      surgery, of subjects treated with surgery preceded by FNAC or with synchronous
      lymph node dissection, and of thyroid cancer diagnosis after surgery. RESULTS:
      The rate of TSH testing was similar, but the rate of imaging was lower in the low
      incidence region. The rate of FNAC was similar, whereas the rate of surgery was
      lower in the low incidence region (34 [95% CI 33; 35 ] vs 80 [95% CI 79; 81 ] per
      100,000 person years in the high incidence region; P < .05). In the low incidence
      region compared to the high incidence region, surgery represented a less chosen
      therapy for euthyroid nodular disease patients (47% [95% CI 46; 48] vs 69% [95%
      CI 68; 70]; P < .05), proportionally more surgery was preceded by FNAC, more
      cancer was diagnosed after total thyroidectomy, and thyroid cancer patients had
      more preoperative FNAC and synchronous lymph node dissection. CONCLUSION:
      Regional variation in thyroid cancer incidence, most marked for low-risk disease,
      is associated with different usage of thyroid imaging and surgery, supporting
      variable detection as a key determinant in geographic variation.

PMID- 23966244
TI  - Pancreatic beta-cell function is a stronger predictor of changes in glycemic
      control after an aerobic exercise intervention than insulin sensitivity.
AB  - CONTEXT: Understanding intersubject variability in glycemic control following
      exercise training will help individualize treatment. OBJECTIVE: Our aim was to
      determine whether this variability is related to training-induced changes in
      insulin sensitivity or pancreatic beta-cell function. DESIGN, SETTING, AND
      PARTICIPANTS: We conducted an observational clinical study of 105 subjects with
      impaired glucose tolerance or type 2 diabetes. INTERVENTIONS AND MAIN OUTCOME
      MEASURES: Individual subject changes in fitness (VO2max), glycemia (glycosylated
      hemoglobin, fasting glucose, oral glucose tolerance test), insulin sensitivity
      (hyperinsulinemic-euglycemic clamp), oral glucose-stimulated insulin secretion
      (GSIS), and disposition index (DI) were measured following 12 to 16 weeks of
      aerobic exercise training. Regression analyses were used to identify
      relationships between variables. RESULTS: After training, 86% of subjects
      increased VO2max and lost weight. Glycosylated hemoglobin, fasting glucose, and 2
      hour oral glucose tolerance test were reduced in 69%, 62%, and 68% of subjects,
      respectively, while insulin sensitivity improved in 90% of the participants.
      Changes in glycemic control were congruent with changes in GSIS such that 66% of
      subjects had a reduction in first-phase GSIS, and 46% had reduced second-phase
      GSIS. Training increased first- and second-phase DI in 83% and 74% of subjects.
      Training-induced changes in glycemic control were related to changes in GSIS (P <
      .05), but not insulin sensitivity or DI, and training-induced improvements in
      glycemic control were largest in subjects with greater pretraining GSIS.
      CONCLUSIONS: Intersubject variability in restoring glycemic control following
      exercise is explained primarily by changes in insulin secretion. Thus, baseline
      and training-induced changes in beta-cell function may be a key determinant of
      training-induced improvements in glycemic control.

PMID- 23966245
TI  - Three novel IGSF1 mutations in four Japanese patients with X-linked congenital
      central hypothyroidism.
AB  - CONTEXT: Congenital central hypothyroidism (C-CH) is a rare disease. We
      investigated the molecular basis of unexplained C-CH in 4 Japanese boys. PATIENTS
      AND METHODS: C-CH was diagnosed by low free T4 and/or T3 and low basal TSH
      concentrations. We used whole-exome sequencing of one patient with C-CH to
      identify potential disease-causing mutations. Thereafter, PCR direct sequencing
      was performed to Identify genetic defects underlying C-CH in 3 more patients. We
      then assessed the effects of mutations identified in the Ig superfamily, member 1
      (IGSF1), gene on protein expression and membrane trafficking. RESULTS: All
      patients had congenital hypothyroidism, and 2 had definitive prolactin
      deficiency. Two patients were detected by neonatal screening. The other patients
      were diagnosed by short stature and failure to thrive. We identified a novel
      nonsense variant in IGSF1 by whole-exome sequencing in patient 1, which was
      confirmed by PCR direct sequencing (p.R1189X). PCR direct sequencing identified
      the identical nonsense mutation in patient 2. Patients 3 and 4 harbored distinct
      missense (p.V1082E) or nonsense (p.Q645X) mutations in IGSF1. The mothers of
      patients 1, 3, and 4 were heterozygous for these mutations. The R1189X mutant,
      which lacks the transmembrane domain, failed to traffic to the plasma membrane.
      V1082E could be observed at the cell surface, but at greatly diminished levels
      relative to the wild-type form of the protein. The severely truncated Q645X
      mutant could not be detected by Western blot. CONCLUSION: Our findings provide
      additional genetic evidence that loss-of-function mutations in IGSF1 cause an X
      linked form of C-CH and variable prolactin deficiency.

PMID- 23966246
TI  - Prenatal famine, birthweight, reproductive performance and age at menopause: the
      Dutch hunger winter families study.
AB  - STUDY QUESTION: Is there an association between acute prenatal famine exposure or
      birthweight and subsequent reproductive performance and age at menopause? SUMMARY
      ANSWER: No association was found between intrauterine famine exposure and
      reproductive performance, but survival analysis showed that women exposed in
      utero were 24% more likely to experience menopause at any age. WHAT IS KNOWN
      ALREADY: Associations between prenatal famine and subsequent reproductive
      performance have been examined previously with inconsistent results. Evidence for
      the effects of famine exposure on age at natural menopause is limited to one
      study of post-natal exposure. STUDY DESIGN, SIZE, DURATION: This cohort study
      included men and women born around the time of the Dutch famine of 1944-1945. The
      study participants (n = 1070) underwent standardized interviews on reproductive
      parameters at a mean age of 59 years. PARTICIPANTS/MATERIALS, SETTING, METHODS:
      The participants were grouped as men and women with prenatal famine exposure (n =
      407), their same-sex siblings (family controls, n = 319) or other men and women
      born before or after the famine period (time controls, n = 344). Associations of
      famine exposure with reproductive performance and menopause were analysed using
      logistic regression and survival analysis with competing risk, after controlling
      for family clustering. MAIN RESULTS AND THE ROLE OF CHANCE: Gestational famine
      exposure was not associated with nulliparity, age at birth of first child,
      difficulties conceiving or pregnancy outcome (all P> 0.05) in men or women. At
      any given age, women were more likely to experience menopause after gestational
      exposure to famine (hazard ratio 1.24; 95% CI 1.03, 1.51). The association was
      not attenuated with an additional control for a woman's birthweight. In this
      study, there was no association between birthweight and age at menopause after
      adjustment for gestational famine exposure. LIMITATIONS, REASON FOR CAUTION: Age
      at menopause was self-reported and assessed retrospectively. The study power to
      examine associations with specific gestational periods of famine exposure and
      reproductive function was limited. WIDER IMPLICATIONS OF THE FINDINGS: Our
      findings support previous results that prenatal famine exposure is not related to
      reproductive performance in adult life. However, natural menopause occurs earlier
      after prenatal famine exposure, suggesting that early life events can affect
      organ function even at the ovarian level. STUDY FUNDING/COMPETING INTEREST(S):
      This study was funded by the NHLBI/NIH (R01 HL-067914). TRIAL REGISTRATION
      NUMBER: Not applicable.

PMID- 23966247
TI  - HTRF analysis of soluble huntingtin in PHAROS PBMCs.
AB  - OBJECTIVE: We measured the levels of mutant huntingtin (mtHtt) and total
      huntingtin (tHtt) in blood leukocytes from Prospective Huntington At-Risk
      Observational Study (PHAROS) subjects at 50% risk of carrying the Huntington
      disease mutation using a homogeneous time-resolved fluorescence (HTRF) assay to
      assess its potential as a biomarker. METHODS: Peripheral blood mononuclear cells
      from consenting PHAROS subjects were analyzed by HTRF using antibodies that
      simultaneously measured mtHtt and tHtt. mtHtt levels were normalized to tHtt,
      double-stranded DNA, or protein and analyzed according to cytosine-adenine
      guanine repeat length (CAGn), demographics, predicted time to clinical onset or
      known time since clinical onset, and available clinical measures. RESULTS: From
      363 assayed samples, 342 met quality control standards. Levels of mtHtt and
      mt/tHtt were higher in 114 subjects with expanded CAG repeats (CAG >= 37)
      compared with 228 subjects with nonexpanded CAG repeats (CAG <37) (p < 0.0001).
      Analysis of relationships to predicted time to onset or to phenoconversion
      suggested that the HTRF signal could mark changes during the Huntington disease
      prodrome or after clinical onset. CONCLUSIONS: The HTRF assay can effectively
      measure mtHtt in multicenter sample sets and may be useful in trials of therapies
      targeting huntingtin.

PMID- 23966248
TI  - Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and
      children.
AB  - The pseudotumor cerebri syndrome (PTCS) may be primary (idiopathic intracranial
      hypertension) or arise from an identifiable secondary cause. Characterization of
      typical neuroimaging abnormalities, clarification of normal opening pressure in
      children, and features distinguishing the syndrome of intracranial hypertension
      without papilledema from intracranial hypertension with papilledema have
      furthered our understanding of this disorder. We propose updated diagnostic
      criteria for PTCS to incorporate advances and insights into the disorder realized
      over the past 10 years. 

PMID- 23966249
TI  - Using AD biomarker research results for clinical care: a survey of ADNI
      investigators.
AB  - OBJECTIVE: To inform whether the Alzheimer's Disease Neuroimaging Initiative
      (ADNI) should change its policy of not returning research results to ADNI
      participants, we surveyed investigators and research staff about disclosing ADNI
      biomarker information to research participants, with particular emphasis on
      amyloid imaging results. METHODS: In April 2012, just before Food and Drug
      Administration approval of the amyloid-binding radiotracer, florbetapir, all ADNI
      investigators and personnel were recruited to complete an anonymous online survey
      that contained fixed choice and free-text questions. RESULTS: Although ADNI
      participants often requested amyloid imaging results (the proportions of
      investigators who reported requests from more than half of their participants
      with normal cognition or mild cognitive impairment were 20% and 22%,
      respectively), across all diagnostic groups, the majority of ADNI investigators
      (approximately 90%) did not return amyloid imaging results to ADNI participants.
      However, the majority of investigators reported that, if the Food and Drug
      Administration approved florbetapir, they would support the return of amyloid
      imaging results to participants with mild cognitive impairment and normal
      cognition, but they emphasized the need for guidance on how to provide these
      results to participants and for research to assess the value of returning results
      as well as how returning results will affect study validity and participant well
      being. CONCLUSIONS: A majority of ADNI investigators support returning amyloid
      imaging results to ADNI participants. The findings that they want guidance on how
      to do this and research on the impact of disclosure suggest how to develop and
      monitor a disclosure process.

PMID- 23966250
TI  - Clinical and biochemical improvements in a patient with MNGIE following enzyme
      replacement.

PMID- 23966251
TI  - Postictal generalized EEG suppression: an inconsistent finding in people with
      multiple seizures.
AB  - OBJECTIVE: To determine the consistency and facilitating cofactors of postictal
      generalized EEG suppression (PGES) of >20 seconds after convulsive seizures (CS),
      a suggested predictor of sudden unexpected death in epilepsy risk. METHODS: We
      retrospectively reviewed video-EEG data of people with >=2 recorded CS. Presence
      and duration of PGES were assessed by 2 independent observers blinded to patient
      status. Intraindividual consistency of PGES >20 seconds was determined and
      correlations with clinical characteristics were analyzed after correction for
      individual effects and the varying number of seizures. RESULTS: One hundred fifty
      four seizures in 59 people were analyzed. PGES >20 seconds was found in 37
      individuals (63%) and 57 (37%) of CS. The proportion of persons in whom PGES
      occurred consistently (presence or absence of PGES >20 seconds in all CS) was
      lower in those with more CS. PGES of >20 seconds was more frequent in seizures
      arising from sleep (odds ratio 3.29, 95% confidence interval 1.21-8.96) and when
      antiepileptic medication was tapered (odds ratio 4.80, 95% confidence interval
      1.27-18.14). CONCLUSION: Apparent PGES consistency was less frequent in people
      with more CS recorded, suggesting that PGES is an inconsistent finding in any one
      individual. Thus, we believe that PGES >20 seconds is not a reliable predictor of
      sudden unexpected death in epilepsy. Sleep and antiepileptic drug reduction
      appear to facilitate the occurrence of PGES.

PMID- 23966252
TI  - Long-term outcomes of epilepsy surgery in Sweden: a national prospective and
      longitudinal study.
AB  - OBJECTIVE: To investigate prospective, population-based long-term outcomes
      concerning seizures and antiepileptic drug (AED) treatment after resective
      epilepsy surgery in Sweden. METHODS: Ten- and 5-year follow-ups were performed in
      2005 to 2007 for 278/327 patients after resective epilepsy surgery from 1995 to
      1997 and 2000 to 2002, respectively. All patients had been prospectively followed
      in the Swedish National Epilepsy Surgery Register. Ninety-three patients, who
      were presurgically evaluated but not operated, served as controls. RESULTS: In
      the long term (mean 7.6 years), 62% of operated adults and 50% of operated
      children were seizure-free, compared to 14% of nonoperated adults (p < 0.001) and
      38% of nonoperated children (not significant). Forty-one percent of operated
      adults and 44% of operated children had sustained seizure freedom since surgery,
      compared to none of the controls (p < 0.0005). Multivariate analysis identified
      >=30 seizures/month at baseline and long epilepsy duration as negative predictors
      and positive MRI to be a positive predictor of long-term seizure-free outcome.
      Ten years after surgery, 86% of seizure-free children and 43% of seizure-free
      adults had stopped AEDs in the surgery groups compared to none of the controls (p
      < 0.0005). CONCLUSIONS: This population-based, prospective study shows good long
      term seizure outcomes after resective epilepsy surgery. The majority of the
      patients who are seizure-free after 5 and 10 years have sustained seizure freedom
      since surgery. Many patients who gain seizure freedom can successfully
      discontinue AEDs, more often children than adults. CLASSIFICATION OF EVIDENCE:
      This study provides Class III evidence that more patients are seizure-free and
      have stopped AED treatment in the long term after resective epilepsy surgery than
      nonoperated epilepsy patients.

PMID- 23966253
TI  - Clinical presentation of chronic traumatic encephalopathy.
AB  - OBJECTIVE: The goal of this study was to examine the clinical presentation of
      chronic traumatic encephalopathy (CTE) in neuropathologically confirmed cases.
      METHODS: Thirty-six adult male subjects were selected from all cases of
      neuropathologically confirmed CTE at the Boston University Center for the Study
      of Traumatic Encephalopathy brain bank. Subjects were all athletes, had no
      comorbid neurodegenerative or motor neuron disease, and had next-of-kin
      informants to provide retrospective reports of the subjects' histories and
      clinical presentations. These interviews were conducted blind to the subjects'
      neuropathologic findings. RESULTS: A triad of cognitive, behavioral, and mood
      impairments was common overall, with cognitive deficits reported for almost all
      subjects. Three subjects were asymptomatic at the time of death. Consistent with
      earlier case reports of boxers, 2 relatively distinct clinical presentations
      emerged, with one group whose initial features developed at a younger age and
      involved behavioral and/or mood disturbance (n = 22), and another group whose
      initial presentation developed at an older age and involved cognitive impairment
      (n = 11). CONCLUSIONS: This suggests there are 2 major clinical presentations of
      CTE, one a behavior/mood variant and the other a cognitive variant.

PMID- 23966255
TI  - Clinical and MRI activity as determinants of sample size for pediatric multiple
      sclerosis trials.
AB  - OBJECTIVE: To estimate sample sizes for pediatric multiple sclerosis (MS) trials
      using new T2 lesion count, annualized relapse rate (ARR), and time to first
      relapse (TTFR) endpoints. METHODS: Poisson and negative binomial models were fit
      to new T2 lesion and relapse count data, and negative binomial time-to-event and
      exponential models were fit to TTFR data of 42 children with MS enrolled in a
      national prospective cohort study. Simulations were performed by resampling from
      the best-fitting model of new T2 lesion count, number of relapses, or TTFR, under
      various assumptions of the effect size, trial duration, and model parameters.
      RESULTS: Assuming a 50% reduction in new T2 lesions over 6 months, 90
      patients/arm are required, whereas 165 patients/arm are required for a 40%
      treatment effect. Sample sizes for 2-year trials using relapse-related endpoints
      are lower than that for 1-year trials. For 2-year trials and a conservative
      assumption of overdispersion (theta), sample sizes range from 70 patients/arm
      (using ARR) to 105 patients/arm (TTFR) for a 50% reduction in relapses, and 230
      patients/arm (ARR) to 365 patients/arm (TTFR) for a 30% relapse reduction.
      Assuming a less conservative theta, 2-year trials using ARR require 45
      patients/arm (60 patients/arm for TTFR) for a 50% reduction in relapses and 145
      patients/arm (200 patients/arm for TTFR) for a 30% reduction. CONCLUSION: Six
      month phase II trials using new T2 lesion count as an endpoint are feasible in
      the pediatric MS population; however, trials powered on ARR or TTFR will need to
      be 2 years in duration and will require multicentered collaboration.

PMID- 23966254
TI  - Priorities in pediatric epilepsy research: improving children's futures today.
AB  - The Priorities in Pediatric Epilepsy Research workshop was held in the spirit of
      patient-centered and patient-driven mandates for developing best practices in
      care, particularly for epilepsy beginning under age 3 years. The workshop brought
      together parents, representatives of voluntary advocacy organizations,
      physicians, allied health professionals, researchers, and administrators to
      identify priority areas for pediatric epilepsy care and research including
      implementation and testing of interventions designed to improve care processes
      and outcomes. Priorities highlighted were 1) patient outcomes, especially seizure
      control but also behavioral, academic, and social functioning; 2) early and
      accurate diagnosis and optimal treatment; 3) role and involvement of parents
      (communication and shared decision-making); and 4) integration of school and
      community organizations with epilepsy care delivery. Key factors influencing
      pediatric epilepsy care included the child's impairments and seizure
      presentation, parents, providers, the health care system, and community systems.
      Care was represented as a sequential process from initial onset of seizures to
      referral for comprehensive evaluation when needed. We considered an alternative
      model in which comprehensive care would be utilized from onset, proactively,
      rather than reactively after pharmacoresistance became obvious. Barriers,
      including limited levels of evidence about many aspects of diagnosis and
      management, access to care--particularly epilepsy specialty and behavioral health
      care--and implementation, were identified. Progress hinges on coordinated
      research efforts that systematically address gaps in knowledge and overcoming
      barriers to access and implementation. The stakes are considerable, and the
      potential benefits for reduced burden of refractory epilepsy and lifelong
      disabilities may be enormous.

PMID- 23966257
TI  - Amyloid imaging: the court of public opinion.
AB  - Human amyloid imaging is one of the great recent translational medicine stories.
      Beginning with the recognition that Thioflavin T derivatives could be used as PET
      tracers, through development of Pittsburgh compound B, to Food and Drug
      Administration (FDA) approval of Florbetapir in 2012, human amyloid imaging has
      held great promise to allow in vivo inclusive diagnosis of Alzheimer disease
      (AD), even though the first principle of amyloid PET is that it functions as a
      surrogate for beta-amyloid pathology, and not necessarily as a surrogate for the
      diagnosis of AD.(1,2.) 

PMID- 23966258
TI  - The calcaneal scarf osteotomy: surgical correction of the adult acquired flatfoot
      deformity and radiographic results.
AB  - PURPOSE: Surgical correction of the adult acquired flatfoot deformity (AAFD) is
      continually evolving. This technique article presents the technique of the
      calcaneal scarf osteotomy (CSO) and radiographic evidence supporting the ability
      of this procedure to correct an AAFD. METHOD: The technique described here is a
      single osteotomy that corrects flatfoot deformity in all 3 planes.
      Retrospectively, medical records were reviewed to identify patients who underwent
      a CSO for surgical correction of AAFD. Pre- and postoperative radiographs were
      reviewed. RESULTS: Thirty patients (32 feet) had an average age of 49.0 +/- 17.2
      years (range = 35-73 years) with an average of 5.7 +/- 2.0 years (range = 1-11
      years) of follow-up. Anteroposterior and lateral radiographic parameters were
      significantly altered with this procedure (P < .001). CSO-induced calcaneal
      cuboid joint arthritis did not occur. DISCUSSION AND CONCLUSIONS: The results of
      the current study demonstrate that the CSO significantly changes radiographic
      exam parameters in patients who suffer from AAFD. Therefore, the CSO provides
      triplanar correction through one osteotomy with early return to weight bearing
      and lacks the complications such as lateral column pain associated with other
      calcaneal osteotomies. LEVELS OF EVIDENCE: Level IV, Retrospective cohort study.

PMID- 23966259
TI  - Multiple tendon ruptures of unknown etiology.
AB  - Tendon ruptures are common findings in foot and ankle practice. The etiology of
      tendon ruptures tends to be multifactorial-usually due to a combination of
      trauma, effects of systemic diseases, adverse effects of medications, and
      obesity. We present an unusual case of right Achilles tendinitis, left Achilles
      tendon rupture, bilateral peroneus longus tendon rupture, and left peroneus
      brevis tendon rupture of unknown etiology. This case report highlights the need
      for research for other possible, lesser known etiologies of tendon pathology.
      LEVEL OF EVIDENCE: Therapeutic, Level IV, Case Study.

PMID- 23966256
TI  - Unawareness of motor phenoconversion in Huntington disease.
AB  - OBJECTIVE: To determine whether Huntington disease (HD) mutation carriers have
      motor symptoms (complaints) when definite motor onset (motor phenoconversion) is
      diagnosed and document differences between the groups with and without
      unawareness of motor signs. METHODS: We analyzed data from 550 HD mutation
      carriers participating in the multicenter PREDICT-HD Study followed through the
      HD prodrome. Data analysis included demographics, the Unified Huntington's
      Disease Rating Scale (UHDRS) and the Participant HD History of symptoms, self
      report of progression, and cognitive, behavioral, and imaging measures.
      Unawareness was identified when no motor symptoms were self-reported but when
      definite motor HD was diagnosed. RESULTS: Of 38 (6.91%) with onset of motor HD,
      almost half (18/38 = 47.36%) had no motor symptoms despite signs of disease on
      the UHDRS motor rating and consistent with unawareness. A group with motor
      symptoms and signs was similar on a range of measures to the unaware group. Those
      with unawareness of HD signs reported less depression. Patients with symptoms had
      more striatal atrophy on imaging measures. CONCLUSIONS: Only half of the patients
      with newly diagnosed motor HD had motor symptoms. Unaware patients were less
      likely to be depressed. Self-report of symptoms may be inaccurate in HD at the
      earliest stage.

PMID- 23966260
TI  - Effectiveness of ankle taping on ankle joint kinematics during walking on level
      ground.
AB  - Prescriptions for functional ankle instability are generally oriented to taping,
      which need to be validated as an efficient treatment. Therefore, the aim of this
      study was to investigate the effectiveness of ankle taping on the subject's foot
      pressure and gait pattern, including mediolateral analysis, according to tape
      application side. A sample of 20 right-handed healthy subjects volunteered to
      participate in this study, which was composed of 3 taping conditions: "with
      taping of the right ankle," "with taping of both ankles," and "with taping of the
      left ankle." Participants were asked to perform a walk on the walkway to get 2
      footprints repeated 6 times. The variables measured were step length, step
      duration, double stance, and swing. The results clearly showed significant change
      in step duration and double phase when tape was applied to the left ankle, F(2,
      54) = 12.03; P < .05. Significant changes were also observed for step length and
      swing when tape was applied to the both ankles, F(2, 54) = 10.71; P < .05]. This
      study showed that double stance and swing phase duration increases, and that the
      pressure is equalized on both feet when taping the unstable ankle. Taping a
      functionally unstable ankle is more likely to improve its stability. LEVELS OF
      EVIDENCE: Therapeutic Level II: Prospective comparative trial.

PMID- 23966261
TI  - Stress fracture of the anterior process of the calcaneus: a case report.
AB  - Stress fracture of the anterior process of the calcaneus is rare. We present a
      case of a 14-year-old female basketball player who suffered a stress fracture of
      the anterior process of the calcaneus that was not associated with a
      calcaneonavicular coalition. After conservative treatment failed, drilling of the
      fracture site was required to facilitate healing. A possible cause of this rare
      type of stress fracture seemed to be a long anterior process of the calcaneus.
      LEVEL OF EVIDENCE: Therapeutic, Level IV: Case study.

PMID- 23966262
TI  - Skin demarcation and amputation level for foot gangrene following meningococcal
      septicemia.
AB  - A case report of a 55-year-old woman who was being considered for bilateral below
      knee or Syme's amputations after gangrene at the level of both forefeet due to
      meningococcal septicaemia is described. An expectant approach for 6 months
      revealed that the tissues deep to the necrotic skin were viable and she was
      subsequently able to mobilize independently with normal footwear after bilateral
      toe amputations at the metatarsophalangeal joint levels. This case and a
      literature review suggest that the demarcation of healthy skin from necrotic skin
      (eschar) should not dictate the level of amputation in dry gangrene of the foot
      following meningococcal septicemia. Magnetic resonance imaging can overestimate
      the degree of muscle necrosis. Treatment should be individualized for each
      patient, but advice should include the option of prolonged conservative treatment
      to preserve limb length and function. LEVEL OF EVIDENCE: Therapeutic, Level IV:
      Case study.

PMID- 23966263
TI  - A clinical and radiological study of peroneal tendon pathology.
AB  - BACKGROUND: The proportion of patients with clinical findings referable to
      peroneal pathology and magnetic resonance imaging (MRI)-diagnosed peroneal tendon
      pathology is unknown. Previous studies have correlated surgical findings with
      clinical data and preoperative MRI, but there are no published studies that
      reference clinical examination findings to imaging findings. PURPOSE: To
      determine the relationship between peroneal tendon pathology as diagnosed by MRI
      and clinical findings of peroneal tendon pathology. METHODS: Fifty-six patients
      who had both MRI evidence of peroneal tendon pathology and an associated clinical
      examination of the ankle were evaluated over a 3-year period at a tertiary care
      institution. Clinical examination criteria included lateral ankle tenderness,
      dislocation/snapping, and lateral ankle pain. A board-certified, fellowship
      trained musculoskeletal radiologist confirmed the presence of MRI findings
      consistent with peroneal tendon pathology. RESULTS: Of the 56 patients with
      positive findings on MRI, 27 patients had an associated positive clinical exam
      and 29 patients had a negative clinical exam. The positive predictive value of
      MRI for peroneal tendon tears with positive clinical findings was 48% (95%
      confidence interval = 35% to 61%). CONCLUSION: Patients with MRI findings of
      peroneal tendon pathology should undergo careful clinical examination, as the
      positive predictive value of MRI for peroneal tendon pathology with actual
      clinical findings is low. This study demonstrates that peroneal tendon tears are
      often incidental findings on MRI.

PMID- 23966264
TI  - Hierarchical hollow spheres of Fe2O3 @polyaniline for lithium ion battery anodes.
AB  - Hierarchical hollow spheres of Fe2 O3 @polyaniline are fabricated by template
      free synthesis of iron oxides followed by a post in- and exterior construction. A
      combination of large surface area with porous structure, fast ion/electron
      transport, and mechanical integrity renders this material attractive as a lithium
      ion anode, showing superior rate capability and cycling performance. 

PMID- 23966265
TI  - Improved MIN6 beta-cell function on self-assembled peptide amphiphile nanomatrix
      inscribed with extracellular matrix-derived cell adhesive ligands.
AB  - Understanding the role of the pancreatic extracellular matrix (ECM) in supporting
      islet survival and function drives the pursuit to create biomaterials that
      imitate and restore the pancreatic ECM microenvironment. To create an ECM mimic
      holding bioinductive cues for beta-cells, self-assembled peptide amphiphiles
      (PAs) inscribed with four selected ECM-derived cell adhesive ligands are
      synthesized. After 7 days, compared to control groups cultured on biologically
      inert substrates, MIN6 beta-cells cultured on PAs functionalized with YIGSR and
      RGDS cell adhesive ligands exhibit elevated insulin secretion in responses to
      glucose and also form beta-cell clusters. These findings suggest that the self
      assembled PA nanomatrix may be utilized to improve pancreatic islet
      transplantation for treating type 1 diabetes. 

PMID- 23966266
TI  - Agomelatine and hepatotoxicity: implications of cumulated data derived from
      spontaneous reports of adverse drug reactions.
AB  - Considering the antidepressant agomelatine (AGM) there is a discrepancy between
      the widespread knowledge of the potential of AGM to cause hepatotoxic adverse
      drug reactions (ADR) and the availability of corresponding published data. This
      impedes an adequate assessment of the hepatotoxicity profile of AGM. We conducted
      a query of the database of a German Medical Regulatory Body (BfArM) and analyzed
      spontaneous reports of hepatotoxic ADR. We identified n=58 cases of AGM-related
      hepatotoxic ADR. Most frequent ADR was asymptomatic increase of liver enzymes
      (79%); n=6 patients (10%) with AGM-related toxic hepatitis were reported.
      Characteristics of patients: female sex (69%), age > 50 years (mean 54 years),
      polypharmacy (57%), and presence of cardiovascular risk factors (58.5%). Most of
      the hepatotoxic ADR (90%) were reported to have improved/recovered after
      discontinuation of AGM. Our evaluation suggests that AGM features a potential to
      cause severe forms of hepatotoxicity and emphasizes that a pre-existing liver
      disease is a contraindication for treatment with AGM. Secondly, increased age,
      female sex and polypharmacy may be risk factors for the development of AGM
      related hepatotoxic ADR. 

PMID- 23966267
TI  - Different contribution of conserved amino acids to the global properties of
      triosephosphate isomerases.
AB  - It is generally assumed that the amino acids that exist in all homologous enzymes
      correspond to residues that participate in catalysis, or that are essential for
      folding and stability. Although this holds for catalytic residues, the function
      of conserved noncatalytic residues is not clear. It is not known if such residues
      are of equal importance and have the same role in different homologous enzymes.
      In humans, the E104D mutation in triosephosphate isomerase (TIM) is the most
      frequent mutation in the autosomal diseases named "TPI deficiencies." We explored
      if the E104D mutation has the same impact in TIMs from four different organisms
      (Homo sapiens, Giardia lamblia, Trypanosoma cruzi, and T. brucei). The catalytic
      properties were not significantly affected by the mutation, but it affected the
      rate and extent of formation of active dimers from unfolded monomers differently.
      Scanning calorimetry experiments indicated that the mutation was in all cases
      destabilizing, but the mutation effect on rates of irreversible denaturation and
      transition-state energetics were drastically dependent on the TIM background. For
      instance, the E104D mutation produce changes in activation energy ranging from
      430 kJ mol(-1) in HsTIM to -78 kJ mol(-1) in TcTIM. Thus, in TIM the role of a
      conserved noncatalytic residue is drastically dependent on its molecular
      background. Accordingly, it would seem that because each protein has a particular
      sequence, and a distinctive set of amino acid interactions, it should be regarded
      as a unique entity that has evolved for function and stability in the organisms
      to which it belongs.

PMID- 23966268
TI  - A novel method for sample delivery and testing of whole blood: gel strip PCR for
      point of care (POC) molecular diagnostics.
AB  - Testing of whole blood in miniaturized PCR is compromised by the opaque nature of
      whole blood that leads to physical masking of a fluorescent signal. We
      demonstrate a method to perform real-time PCR with whole blood that avoids
      interference from the opacity of whole blood. 

PMID- 23966269
TI  - Consistent response of vegetation dynamics to recent climate change in tropical
      mountain regions.
AB  - Global climate change has emerged as a major driver of ecosystem change. Here, we
      present evidence for globally consistent responses in vegetation dynamics to
      recent climate change in the world's mountain ecosystems located in the pan
      tropical belt (30 degrees N-30 degrees S). We analyzed decadal-scale trends and
      seasonal cycles of vegetation greenness using monthly time series of satellite
      greenness (Normalized Difference Vegetation Index) and climate data for the
      period 1982-2006 for 47 mountain protected areas in five biodiversity hotspots.
      The time series of annual maximum NDVI for each of five continental regions shows
      mild greening trends followed by reversal to stronger browning trends around the
      mid-1990s. During the same period we found increasing trends in temperature but
      only marginal change in precipitation. The amplitude of the annual greenness
      cycle increased with time, and was strongly associated with the observed increase
      in temperature amplitude. We applied dynamic models with time-dependent
      regression parameters to study the time evolution of NDVI-climate relationships.
      We found that the relationship between vegetation greenness and temperature
      weakened over time or was negative. Such loss of positive temperature sensitivity
      has been documented in other regions as a response to temperature-induced
      moisture stress. We also used dynamic models to extract the trends in vegetation
      greenness that remain after accounting for the effects of temperature and
      precipitation. We found residual browning and greening trends in all regions,
      which indicate that factors other than temperature and precipitation also
      influence vegetation dynamics. Browning rates became progressively weaker with
      increase in elevation as indicated by quantile regression models. Tropical
      mountain vegetation is considered sensitive to climatic changes, so these
      consistent vegetation responses across widespread regions indicate persistent
      global-scale effects of climate warming and associated moisture stresses. 

PMID- 23966270
TI  - A benchmarking method to measure dietary absorption efficiency of chemicals by
      fish.
AB  - Understanding the dietary absorption efficiency of chemicals in the
      gastrointestinal tract of fish is important from both a scientific and a
      regulatory point of view. However, reported fish absorption efficiencies for well
      studied chemicals are highly variable. In the present study, the authors
      developed and exploited an internal chemical benchmarking method that has the
      potential to reduce uncertainty and variability and, thus, to improve the
      precision of measurements of fish absorption efficiency. The authors applied the
      benchmarking method to measure the gross absorption efficiency for 15 chemicals
      with a wide range of physicochemical properties and structures. They selected
      2,2',5,6'-tetrachlorobiphenyl (PCB53) and decabromodiphenyl ethane as absorbable
      and nonabsorbable benchmarks, respectively. Quantities of chemicals determined in
      fish were benchmarked to the fraction of PCB53 recovered in fish, and quantities
      of chemicals determined in feces were benchmarked to the fraction of
      decabromodiphenyl ethane recovered in feces. The performance of the benchmarking
      procedure was evaluated based on the recovery of the test chemicals and precision
      of absorption efficiency from repeated tests. Benchmarking did not improve the
      precision of the measurements; after benchmarking, however, the median recovery
      for 15 chemicals was 106%, and variability of recoveries was reduced compared
      with before benchmarking, suggesting that benchmarking could account for
      incomplete extraction of chemical in fish and incomplete collection of feces from
      different tests.

PMID- 23966271
TI  - Visualization of hypoxia-inducible factor 1alpha-p300 interactions in live cells
      by fluorescence resonance energy transfer.
AB  - Hypoxia-inducible factor (HIF)-1alpha mediates the hypoxia response signaling
      pathway essential for maintaining cellular homeostasis in low oxygen environments
      through its complex formation with CBP/p300 in the nucleus. Employing
      fluorescence resonance energy transfer (FRET), we devised a live-cell interaction
      assay based on reporter proteins by tagging fluorescent proteins onto the carboxy
      termini of HIF-1alpha and p300. The nature of the constructed reporter protein
      was verified by observing localized distribution, degradation, and stabilization
      kinetics in cells transfected with the HIF-1alpha containing plasmid. A mutant
      HIF-1alpha incapable of binding to p300 was then utilized to demonstrate
      insignificant FRET efficiency, thereby confirming that our constructs could
      effectively probe the direct interaction between HIF-1alpha and p300. We further
      examined the effects of small molecules known to modulate the HIF-1alpha-p300
      interaction and transcriptional activity on FRET. Finally, by inhibiting
      activities of two HIF-specific hydroxylases, HIF-specific prolyl hydroxylase
      (PHD) 2 and factor inhibiting HIF-1 (FIH-1) with their specific siRNAs, we
      explored how these HIF-specific hydroxylases contribute to the HIF-1alpha-p300
      interaction by FRET measurements along with HIF-1 mediated transcriptional
      activation. Therefore, this technique would provide a way to study selective
      inhibition of either PHD2 or FIH-1 within living cells, and to screen specific
      inhibitors of HIF-mediated transcription activity for therapeutic applications.

PMID- 23966273
TI  - The viscosity law of dendronized linear polymers.
AB  - The intrinsic viscosity [eta] of dendronized linear macromolecules dissolved in
      thermodynamically good solvents depends both on chain length that is contour
      length L(c) of the backbone of the polymer and on the persistence length l(p).
      Investigating a set of samples of identical L(c) but differing in the generation
      number for which data on lp are available, it becomes possible to establish a
      generalized viscosity law in the form [eta] = K(M/M(p))(alpha) in which M(p)
      denotes the molar mass of the objects per l(p), M is the total molar mass, K is a
      constant, and alpha is the Mark-Howink exponent, which is found to be 0.55.

PMID- 23966274
TI  - HIV testing sites' communication about adolescent confidentiality: potential
      barriers and facilitators to testing.
AB  - PURPOSE: This study sought to evaluate HIV testing locations in New York City in
      terms of staff communication of confidentiality policies for adolescent clients.
      METHOD: Using the New York State Directory of HIV Counseling and Testing
      Resources as a sampling frame, this study made telephone contact with 164 public
      HIV testing locations in New York City and used a semistructured interview to ask
      questions about confidentiality, parental permission, and parent access to test
      results. RESULTS: At 48% of locations, either HIV testing was not offered or we
      were unable to reach a staff member to ask questions about testing options and
      confidentiality. At the remaining sites, information provided regarding
      confidentiality, parental consent, and privacy of test results was correct only
      69% to 85% of the time. Additionally, 23% of sites successfully contacted offered
      testing exclusively between 9:00 a.m. and 3:00 p.m. weekdays, when most
      adolescents are in school. CONCLUSIONS: Our findings point to a need for
      increased training and quality control at the clinical level to ensure that
      consumers in need of HIV testing are provided with accurate information and
      accessible services. Furthermore, these results highlight the need for more
      "patient-centric" sites with enhanced accessibility for potential clients,
      particularly youth.

PMID- 23966272
TI  - Dendritic cell subsets in the intestinal lamina propria: ontogeny and function.
AB  - The intestinal mucosa is exposed to large amounts of foreign antigen (Ag) derived
      from commensal bacteria, dietary Ags, and intestinal pathogens. Dendritic cells
      (DCs) are believed to be involved in the induction of tolerance to harmless Ags
      and in mounting protective immune responses to pathogens and, as such, to play
      key roles in regulating intestinal immune homeostasis. The characterization of
      classical DCs (cDCs) in the intestinal lamina propria has been under intense
      investigation in recent years but the use of markers (including CD11c, CD11b, MHC
      class II), which are also expressed by intestinal MPhis, has led to some
      controversy regarding their definition. Here we review recent studies that help
      to distinguish cDCs subsets from monocyte-derived cells in the intestinal mucosa.
      We address the phenotype and ontogeny of these cDC subsets and highlight recent
      findings indicating that these subsets play distinct roles in the regulation of
      mucosal immune responses in vivo. 

PMID- 23966275
TI  - Absolute quantitation of sub-micrometer particles in cells by flow cytometry.
AB  - Absolute quantitative measurements of nanoparticle (NP) uptake are a prerequisite
      to determine doses of NPs in pharmacological and toxicological studies. However,
      absolute quantitation is rarely reported, hindering the comparison between
      different studies. Here, a new flow cytometric approach is presented to analyze
      fluorescent NPs with a "standard" non-scanning flow cytometer and to quantify
      them inside cells. The mean fluorescence intensity of a single particle and the
      particle concentration (NPs per MUL medium) are obtained. A routine for rapid
      quantitative counting of the endocytosed NPs in HeLa cells by flow cytometry (FC)
      is developed and validated by confocal laser scanning microscopy. As a proof-of
      concept, the quantitative measurements show that the cellular uptake efficiency
      of negatively charged poly(methyl methacrylate) NPs is very low, that is, in the
      range of 10(-3) % of the added particle amount. 

PMID- 23966276
TI  - [The Dresden Body Image Inventory (DKB-35): validity in a clinical sample].
AB  - The Dresden Body Image Questionnaire (DKB-35) measures 5 dimensions of body
      image: vitality, self-acceptance, self-aggrandisement, physical closeness, and
      sexual fulfilment. This article presents data on the reliability and validity of
      the DKB-35. The sample consisted of 560 pa-tients with psychosomatic disorders.
      To analyse the factor structure, a confirmatory factor analysis was conducted. To
      examine the convergent validity, correlations between the DKB-35 scales and the
      Frankfurt Body Concept Scales (FKKS, [1]), the Narcissism Personality Inventory
      (NPI, [2]) and the self-esteem subscale of the Frankfurt Self-Concept Scales
      (FSKN, [3]) were computed. The 5 scales of the DKB-35 showed excellent
      reliability. Between the 5 DKB-35 scales and the corresponding scales of the
      FKKS, the NPI, and the FSKN, moderate correlations were found. The results
      confirm the reliability and validity of the DKB-35. Possible fields of
      applications and further developments are discussed. 

PMID- 23966277
TI  - [Resources needed to ensure inpatient psycho-oncological care].
AB  - The aim of this study was to document how many patients with malignant diseases
      in an acute care hospital can be supported by one full time psycho-oncologist and
      how long each procedure takes. Over the course of 2 years, frequency and duration
      of all interventions provided by a psycho-oncologist were documented at 6
      hospitals in Germany. A total of 4 947 patients received 20 366 psycho
      oncological interventions. One full time position could care for 351 (1st year)
      and 436 (2nd year) patients respectively. The most frequent intervention was
      supportive counselling to single patients (22%) with an average duration of 29
      min. Patients received on average 4 consultations. In addition, many short
      contacts with a duration of 10 min were provided. On average, psycho-oncological
      care could be provided by a person with a full-time position to 393 patients with
      malignant diseases. Most of the consultations were of short duration (10-30 min).

PMID- 23966278
TI  - [Parenthood and cancer: dyadic analysis of psychological distress and -health
      related quality of life of cancer parents with minor children].
AB  - The purpose of this study was the analysis of psychological distress and health
      related quality of life (HRQoL) of parents with minor children during curative
      resp. palliative treatment.Cross-sectional design with a sample of N=89 parent
      dyads. Dyadic analysis of demographic, illness and family variables via mixed
      linear models.Patients and healthy partners indicated psychological distress on
      different subscales. Intradyadic correlations were small-moderate. Most important
      predictors of psychological distress and HRQoL were treatment stadium, gender,
      family functioning, and employment status.Dependent on demographic variables,
      psychooncological support was evident mainly for parents in palliative care and
      for families with dysfunctional functioning. 

PMID- 23966279
TI  - [Obesity and symptoms of depression and anxiety in pre- and postmenopausal women:
      a comparison of different obesity indicators].
AB  - This study examines differences in the rates of depression and anxiety symptoms
      in overweight vs. normal weight women before and after the menopause. In a
      population sample of 1 416 participants of the KORA-Survey F3 2004-2005 (age 35
      74 years), body mass index (BMI), waist circumference (WC), waist-to-hip-ratio
      (WHR) und waist-to-height-ratio (WHtR) were measured via physical examination.
      Depression and anxiety were assessed with the Hospital Anxiety and Depression
      Scale. Compared with normal weight, obesity was associated with depression in
      premenopausal women. This held for elevated BMI-, WC- and WHtR-scores (OR=3.7,
      4.2, and 2.8), underlining the relevance of both general and abdominal obesity.
      Menopausal status may be a moderator for the association of obesity and
      depression, which - given the interaction between these 2 risk factors - may be
      of preventive importance in regard to the development of cardiovascular outcomes
      such as coronary heart disease.

PMID- 23966280
TI  - Photosynthetic and cellular toxicity of cadmium in Chlorella vulgaris.
AB  - The toxic effects of cadmium (Cd) on the green alga Chlorella vulgaris were
      investigated by following the response to Cd of various toxicity endpoints (cell
      growth, cell size, photochemical efficiency of PSII in the light or Phi(PSII),
      maximal photochemical efficiency or Fv/Fm, chlorophyll a fluorescence, esterase
      activity, and cell viability). These toxicity endpoints were studied in
      laboratory batch cultures of C. vulgaris over a long-term 96-h exposure to
      different Cd concentrations using flow cytometry and pulse amplitude modulated
      fluorometry. The sequence of sensitivity of these toxicity endpoints was: cell
      yield >> Phi(PSII) ~ esterase activity > Fv/Fm > chlorophyll a fluorescence ~
      cell viability. It is shown that cell apoptosis or cell death only accounted for
      a minor part of the reduction in cell yield even at very high algistatic free
      Cd2+ concentrations, and other mechanisms such as blocked cell divisions are
      major contributors to cell yield inhibition. Furthermore, cadmium may affect both
      the electron donors and acceptors of the electron transport chain at high free
      Cd2+ concentration. Finally, the resistance of cells to cell death was size
      dependent; medium-sized cells had the highest toxicity threshold. The present
      study brings new insights into the toxicity mechanisms of Cd in C. vulgaris and
      provides a detailed comparison of the sensitivity of various Cd toxicity
      endpoints.

PMID- 23966281
TI  - Basin-scale phenology and effects of climate variability on global timing of
      initial seaward migration of Atlantic salmon (Salmo salar).
AB  - Migrations between different habitats are key events in the lives of many
      organisms. Such movements involve annually recurring travel over long distances
      usually triggered by seasonal changes in the environment. Often, the migration is
      associated with travel to or from reproduction areas to regions of growth. Young
      anadromous Atlantic salmon (Salmo salar) emigrate from freshwater nursery areas
      during spring and early summer to feed and grow in the North Atlantic Ocean. The
      transition from the freshwater ('parr') stage to the migratory stage where they
      descend streams and enter salt water ('smolt') is characterized by morphological,
      physiological and behavioural changes where the timing of this parr-smolt
      transition is cued by photoperiod and water temperature. Environmental conditions
      in the freshwater habitat control the downstream migration and contribute to
      within- and among-river variation in migratory timing. Moreover, the timing of
      the freshwater emigration has likely evolved to meet environmental conditions in
      the ocean as these affect growth and survival of the post-smolts. Using
      generalized additive mixed-effects modelling, we analysed spatio-temporal
      variations in the dates of downstream smolt migration in 67 rivers throughout the
      North Atlantic during the last five decades and found that migrations were
      earlier in populations in the east than the west. After accounting for this
      spatial effect, the initiation of the downstream migration among rivers was
      positively associated with freshwater temperatures, up to about 10  degrees C and
      levelling off at higher values, and with sea-surface temperatures. Earlier
      migration occurred when river discharge levels were low but increasing. On
      average, the initiation of the smolt seaward migration has occurred 2.5 days
      earlier per decade throughout the basin of the North Atlantic. This shift in
      phenology matches changes in air, river, and ocean temperatures, suggesting that
      Atlantic salmon emigration is responding to the current global climate changes. 

PMID- 23966282
TI  - Fecal microbiota transplantation and emerging treatments for Clostridium
      difficile infection.
AB  - Due to the increased incidence and recurrence of Clostridium difficile infection,
      health care providers are seeking new and alternative treatments to the standard
      antibiotic therapy. The objective of this article is to present a review on the
      background, microbiologic efficacy, clinical efficacy, and safety of fecal
      microbiota transplantation and to provide an overview of emerging treatment
      options currently under investigation. Emerging treatment options discussed
      include the use of monoclonal antibodies directed against toxins A and B, C
      difficile vaccination, and transplantation of nontoxigenic C difficile strains. 

PMID- 23966283
TI  - Management of comorbidities in diabetics with renal cell carcinoma: past
      utilization and current outcomes.
AB  - OBJECTIVES: This study evaluated whether particular diabetes mellitus (DM),
      hyperlipidemia, or hypertension pharmacotherapy was associated with improved
      renal cell carcinoma (RCC) outcomes in diabetics with emergent RCC. METHODS: All
      DM cases newly diagnosed with RCC at Roswell Park Cancer Institute (January 01,
      2003-December 31, 2010) were included (n = 95). Baseline demographic information,
      clinical history, and cancer outcomes were documented after chart review.
      Fisher's test was used for the analysis of categorical outcomes across different
      treatment groups. Univariate and multivariate analyses for the comparisons of the
      overall survival and progression-free survival across treatment groups were
      assessed using Kaplan-Meier log-rank test and Cox proportional hazards models.
      RESULTS: We found that DM pharmacotherapy users, which may represent a more
      advanced disease as compared to those controlled by diet alone, displayed
      significantly greater mortality (P = .01). Additionally, we found that
      cholesterol-lowering pharmacotherapy use was associated with decreased RCC
      mortality (hazard ratio = 0.54, P = .06). Individuals receiving combined
      hypertension regimens had a lower chance to present with baseline metastasis;
      however, hypertension pharmacotherapy use added no survival benefit. CONCLUSION:
      Reinforcing guidelines compliance for hyperlipidemia management in patients with
      DM may provide a considerable cancer benefit if diagnosed with RCC. Studies
      evaluating the need for cholesterol-lowering pharmacotherapy in guidelines
      noncompliant DM cases upon RCC diagnosis are currently needed.

PMID- 23966284
TI  - Primary lymphoepithelioma-like carcinoma of salivary gland: sixty-nine cases with
      long-term follow-up.
AB  - BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) in the salivary glands is a
      rare but unique malignancy. METHODS: Sixty-nine patients with salivary gland LELC
      with long-term follow-up were reviewed for this study. RESULTS: There were 52
      cases in the parotid gland and 17 cases in the submandibular gland. All patients
      underwent complete tumor excision, 41 underwent neck dissection, and 39 received
      postoperative radiotherapy. The 5-year, 10-year, and 15-year overall survival
      (OS) rates were 90%, 75%, and 54%, respectively. Patients with higher
      neutrophil/lymphocyte ratio (NLR >= 4.0) and advanced stage (stage III and IV)
      had significantly poorer OS. Patients who received postoperative radiotherapy had
      significantly better relapse-free survival (RFS). In multivariate analysis,
      stage, NLR, and neck dissection were associated independently with OS, whereas
      stage and postoperative radiotherapy were associated independently with RFS.
      CONCLUSION: Salivary gland LELC is a rare malignancy with a better prognosis that
      partially attributes to surgery with neck dissection and postoperative
      radiotherapy. Preoperative NLR is an independent prognostic factor.

PMID- 23966285
TI  - Synthesis of 6-O-poly(epsilon-caprolactone)-L-ascorbic acid and its controlled
      release from supramolecular polymer micelles.
AB  - Lipophilic 6-O-poly (epsilon-caprolactone)-L-ascorbic acid (AA-6-PCL) is
      synthesized through ROP of epsilon-caprolactone (CL). The number of repeating CL
      units in the polymer chain varies from 6 to 19. AA-6-PCL loaded supramolecular
      polymer micelles (SMPMs) are constructed with beta-cyclodextrin (beta-CD) and PCL
      as blocks. Transmission electron microscopy images show a nanospheric morphology
      of the micelles with a size range of 43.3 +/- 5.0 nm. The drug loading contents
      are 22.53-39.23% for AA-6-PCL. AA-6-PCL exhibits high radical scavenging capacity
      (93.96-96.73%) and efficient scavenging potency, and a cytotoxicity study proves
      the excellent cytocompatibility of AA-6-PCL loaded beta-CD/PCL SMPMs, which
      altogether herald their potential application in the study of the induced
      pluripotent stem cells. 

PMID- 23966286
TI  - Displaced patella fractures.
AB  - Displaced patella fractures often result in disruption of the extensor mechanism
      of the knee. An intact extensor mechanism is a requirement for unassisted gait.
      Therefore, operative treatment of the displaced patella fracture is generally
      recommended. The evaluation of the patella fracture patient includes examination
      of extensor mechanism integrity. Operative management of patella fractures
      normally includes open reduction with internal fixation, although partial
      patellectomy is occasionally performed, with advancement of quadriceps tendon or
      patellar ligament to the fracture bed. Open reduction with internal fixation has
      historically been performed utilizing anterior tension band wiring, although
      comminution of the fracture occasionally makes this fixation construct
      inadequate. Supplementation or replacement of the tension band wire construct
      with interfragmentary screws, cerclage wire or suture, and/or plate-and-screw
      constructs may add to the stability of the fixation construct. Arthrosis of the
      patellofemoral joint is very common after healing of patella fractures, and
      substantial functional deficits may persist long after fracture healing has
      occurred. 

PMID- 23966287
TI  - Elaborations on sexual assault on dates among Israeli students: risk, detrimental
      effect, and resilience factors.
AB  - The current study of 668 Israeli male and female students examines the prevalence
      of gendered risk factors for sexual assault (SA) on dates, posttraumatic stress
      disorder (PTSD) as a detrimental effect of SA, and self-efficacy as resiliency to
      refuse unwanted sex following SA. Two different sets of risk factors that
      increased the likelihood of SA on dates emerged from the hierarchical regression.
      Sexual experience, use of drugs, and private location increased the risk of being
      SA victims among males, whereas sexual experience, perceived provocative
      behavior, and alcohol use increased the risk among females. In addition, PTSD and
      self-efficacy to refuse unwanted sex following SA on dates were predicted by the
      extent of coercive sexual victimization. PTSD was also predicted by subjective
      perception of sexual behavior and rape myths, whereas efficacy was predicted by
      private location. The findings contribute to the literature by showing the
      contribution of various risk factors to experiencing SA, and by showing SA effect
      on PTSD and self-efficacy. 

PMID- 23966288
TI  - Enhanced wear and corrosion in modular tapers in total hip replacement is
      associated with the contact area and surface topography.
AB  - Widespread concern exists about adverse tissue reactions after metal-on-metal
      (MoM) total hip replacement (THR). Concerns have also been expressed with wear
      and corrosion of taper junctions in THR. We report the effect of surface finish
      and contact area associated with a single combination of materials of modular
      tapers. In an in vitro test, we investigated the head/neck (CoCrMo/Ti) interface
      of modular THRs using commercially available heads. Wear and corrosion of taper
      surfaces was compared following a 10 million loading cycle. Surface parameters
      and profiles were measured before and after testing. Electrochemical static and
      dynamic corrosion tests were performed under loaded and non-loaded conditions.
      After the load test, the surface roughness parameters on the head taper were
      significantly increased where the head/neck contact area was reduced. Similarly,
      the surface roughness parameters on the head taper were significantly increased
      where rough neck tapers were used. Corrosion testing showed breaching of the
      passive film on the rough but not the smooth neck tapers. Thus, surface area and
      surface finish are important factors in wear and corrosion at modular interfaces.

PMID- 23966289
TI  - Dynamic interactions between memory systems.

PMID- 23966290
TI  - Modeling daily flowering probabilities: expected impact of climate change on
      Japanese cherry phenology.
AB  - Understanding the drivers of phenological events is vital for forecasting
      species' responses to climate change. We developed flexible Bayesian survival
      regression models to assess a 29-year, individual-level time series of flowering
      phenology from four taxa of Japanese cherry trees (Prunus spachiana, Prunus *
      yedoensis, Prunus jamasakura, and Prunus lannesiana), from the Tama Forest Cherry
      Preservation Garden in Hachioji, Japan. Our modeling framework used time-varying
      (chill and heat units) and time-invariant (slope, aspect, and elevation) factors.
      We found limited differences among taxa in sensitivity to chill, but earlier
      flowering taxa, such as P. spachiana, were more sensitive to heat than later
      flowering taxa, such as P. lannesiana. Using an ensemble of three downscaled
      regional climate models under the A1B emissions scenario, we projected shifts in
      flowering timing by 2100. Projections suggest that each taxa will flower about 30
      days earlier on average by 2100 with 2-6 days greater uncertainty around the
      species mean flowering date. Dramatic shifts in the flowering times of cherry
      trees may have implications for economically important cultural festivals in
      Japan and East Asia. The survival models used here provide a mechanistic modeling
      approach and are broadly applicable to any time-to-event phenological data, such
      as plant leafing, bird arrival time, and insect emergence. The ability to
      explicitly quantify uncertainty, examine phenological responses on a fine time
      scale, and incorporate conditions leading up to an event may provide future
      insight into phenologically driven changes in carbon balance and ecological
      mismatches of plants and pollinators in natural populations and horticultural
      crops. 

PMID- 23966291
TI  - FOXO transcription factors control E2F1 transcriptional specificity and apoptotic
      function.
AB  - The transcription factor E2F1 is a key regulator of proliferation and apoptosis
      but the molecular mechanisms that mediate these cell fate decisions remain
      unclear. Here, we identify FOXO transcription factors as E2F1 target genes that
      act in a feed-forward regulatory loop to reinforce gene induction of multiple
      apoptotic genes. We found that E2F1 forms a complex with FOXO1 and FOXO3. RNAi
      mediated silencing of FOXO impaired E2F1 binding to the promoters of cooperative
      target genes. A FOXO3 mutant insensitive to inactivation by survival kinases
      rescued the inhibitory effect of growth factor signaling on E2F1-mediated
      transcription and apoptosis. The E2F1/FOXO axis is frequently blocked in cancer,
      as evidenced by the specific downregulation of the FOXO-dependent E2F1
      transcriptional program in multiple cancer types and by the association of a
      reduced E2F1/FOXO transcriptional program with poor prognosis. HDAC and
      phosphoinositide 3-kinase (PI3K) inhibitors were identified as specific
      activators of E2F1/FOXO transcription, acting to enhance E2F1-induced apoptosis
      in a FOXO3-dependent manner. Notably, combining the histone deacetylase inhibitor
      vorinostat with a PI3K inhibitor led to enhanced FOXO-dependent apoptosis.
      Collectively, our results identify E2F1/FOXO cooperation as a regulatory
      mechanism that places E2F1 apoptotic activity under the control of survival
      signaling. Therapeutic reactivation of this tumor suppressive mechanism may offer
      a novel broad-acting therapy for cancer.

PMID- 23966292
TI  - EGFR-activating mutations correlate with a Fanconi anemia-like cellular phenotype
      that includes PARP inhibitor sensitivity.
AB  - In patients with lung cancer whose tumors harbor activating mutations in the EGF
      receptor (EGFR), increased responses to platinum-based chemotherapies are seen
      compared with wild-type cancers. However, the mechanisms underlying this
      association have remained elusive. Here, we describe a cellular phenotype of
      cross-linker sensitivity in a subset of EGFR-mutant lung cancer cell lines that
      is reminiscent of the defects seen in cells impaired in the Fanconi anemia
      pathway, including a pronounced G2-M cell-cycle arrest and chromosomal radial
      formation. We identified a defect downstream of FANCD2 at the level of
      recruitment of FAN1 nuclease and DNA interstrand cross-link (ICL) unhooking. The
      effect of EGFR mutation was epistatic with FANCD2. Consistent with the known role
      of FANCD2 in promoting RAD51 foci formation and homologous recombination repair
      (HRR), EGFR-mutant cells also exhibited an impaired RAD51 foci response to ICLs,
      but not to DNA double-strand breaks. EGFR kinase inhibition affected RAD51 foci
      formation neither in EGFR-mutant nor wild-type cells. In contrast, EGFR depletion
      or overexpression of mutant EGFR in wild-type cells suppressed RAD51 foci,
      suggesting an EGFR kinase-independent regulation of DNA repair. Interestingly,
      EGFR-mutant cells treated with the PARP inhibitor olaparib also displayed
      decreased FAN1 foci induction, coupled with a putative block in a late HRR step.
      As a result, EGFR-mutant lung cancer cells exhibited olaparib sensitivity in
      vitro and in vivo. Our findings provide insight into the mechanisms of cisplatin
      and PARP inhibitor sensitivity of EGFR-mutant cells, yielding potential
      therapeutic opportunities for further treatment individualization in this
      genetically defined subset of lung cancer.

PMID- 23966293
TI  - Integrin alphavbeta3 and fibronectin upregulate Slug in cancer cells to promote
      clot invasion and metastasis.
AB  - The blood clotting cascade is selectively involved in lung metastasis, but the
      reason for this selectivity is unclear. Here, we show that tumor cells that
      metastasize predominantly to the lung, such as renal cell carcinoma (RCC) and
      soft tissue sarcoma (STS), have an inherent capacity to generate extensive
      invadopodia when embedded in a blood clot. Compared with other metastatic cancer
      cells tested, RCC and STS cells exhibited increased levels of expression of
      fibronectin and an activated form of the integrin alphavbeta3, which coordinately
      supported the generation of an elaborate fibronectin matrix and actin stress
      fibers in fibrin-embedded tumor cells. Together, fibronectin and alphavbeta3
      induced upregulation of the transcription factor Slug, which mediates epithelial
      mesenchymal transition as well as fibrin invasion and lung metastasis. This
      mechanism is clinically significant, because primary cancer cells from patients
      with metastatic RCC strongly invaded fibrin and this correlated with fibronectin
      matrix formation and Slug expression. In contrast, tumor cells from patients with
      localized RCC were largely noninvasive. Together, our findings establish that
      activated integrin alphavbeta3 and fibronectin promote lung metastasis by
      upregulating Slug, defining a mechanism through which cancer cells can colonize
      blood clots in the lung vasculature.

PMID- 23966294
TI  - Targeting FSTL1 prevents tumor bone metastasis and consequent immune dysfunction.
AB  - Bone metastasis greatly deteriorates the quality of life in patients with cancer.
      Although mechanisms have been widely investigated, the relationship between
      cancer bone metastasis and antitumor immunity in the host has been much less
      studied. Here, we report a novel mechanism of bone metastasis mediated by FSTL1,
      a follistatin-like glycoprotein secreted by Snail(+) tumor cells, which
      metastasize frequently to bone. We found that FSTL1 plays a dual role in bone
      metastasis-in one way by mediating tumor cell invasion and bone tropism but also
      in a second way by expanding a population of pluripotent mesenchymal stem-like
      CD45(-)ALCAM(+) cells derived from bone marrow. CD45(-)ALCAM(+) cells induced
      bone metastasis de novo, but they also generated CD8(low) T cells with weak CTL
      activity in the periphery, which also promoted bone metastasis in an indirect
      manner. RNA interference-mediated attenuation of FSTL1 in tumor cells prevented
      bone metastasis along with the parallel increase in ALCAM(+) cells and CD8(low) T
      cells. These effects were accompanied by heightened antitumor immune responses in
      vitro and in vivo. In clinical specimens of advanced breast cancer, ALCAM(+)
      cells increased with FSTL1 positivity in tumor tissues, but not in adjacent
      normal tissues, consistent with a causal connection between these molecules. Our
      findings define FSTL1 as an attractive candidate therapeutic target to prevent or
      treat bone metastasis, which remains a major challenge in patients with cancer.

PMID- 23966296
TI  - Novel insights into appropriate encapsulation methods for bioactive compounds
      into polymers: a study with peptides and HDAC inhibitors.
AB  - The use of different nanoparticles (NPs) for successful encapsulation of
      bioactive substances is discussed. The inclusion efficiency into liposomes,
      acetalated dextran (Ac-Dex), and variants of poly[(lactic acid)-co-(glycolic
      acid)] (PLGA) NPs is analyzed after chemical degradation. Efficient inclusion of
      SIRT1 inhibitor Ex527 in liposomes, Ac-Dex- and PLGA-NPs is observed for all
      procedures used. Activity of Ex527 is demonstrated by monitoring the acetylation
      status of SIRT1-target p53. In contrast, small peptides are only incorporated
      into acid-terminated PLGA-NPs and marginally into Ac-Dex-NPs. The yield depends
      on peptide sequence and terminal modifications. Activity is exemplified for
      angiotensin II using the dynamic mass redistribution technology. 

PMID- 23966295
TI  - Activation of MAPK pathways due to DUSP4 loss promotes cancer stem cell-like
      phenotypes in basal-like breast cancer.
AB  - Basal-like breast cancer (BLBC) is an aggressive disease that lacks a clinically
      approved targeted therapy. Traditional chemotherapy is effective in BLBC, but it
      spares the cancer stem cell (CSC)-like population, which is likely to contribute
      to cancer recurrence after the initial treatment. Dual specificity phosphatase-4
      (DUSP4) is a negative regulator of the mitogen-activated protein kinase (MAPK)
      pathway that is deficient in highly aggressive BLBCs treated with chemotherapy,
      leading to aberrant MAPK activation and resistance to taxane-induced apoptosis.
      Herein, we investigated how DUSP4 regulates the MAP-ERK kinase (MEK) and c-jun
      NH2-kinase (JNK) pathways in modifying CSC-like behavior. DUSP4 loss increased
      mammosphere formation and the expression of the CSC-promoting cytokines
      interleukin (IL)-6 and IL-8. These effects were caused in part by loss of control
      of the MEK and JNK pathways and involved downstream activation of the ETS-1 and c
      JUN transcription factors. Enforced expression of DUSP4 reduced the CD44(+)/CD24(
      ) population in multiple BLBC cell lines in a MEK-dependent manner, limiting
      tumor formation of claudin-low SUM159PT cells in mice. Our findings support the
      evaluation of MEK and JNK pathway inhibitors as therapeutic agents in BLBC to
      eliminate the CSC population.

PMID- 23966297
TI  - Research for universal health coverage.

PMID- 23966298
TI  - Skinflammation and drug toxicity--a delicate balance.
AB  - Loss of epidermal growth factor receptor function in epidermal keratinocytes
      triggers a disfiguring acneiform rash through the coordinate activation of innate
      and adaptive immune defense mechanisms (Mascia et al. and Lichtenberger et al.,
      this issue). 

PMID- 23966299
TI  - Genetic ablation of epidermal EGFR reveals the dynamic origin of adverse effects
      of anti-EGFR therapy.
AB  - Cancer patients treated with anti-EGFR (epidermal growth factor receptor) drugs
      often develop a dose-limiting pruritic rash of unknown etiology. The aims of our
      study were to define causal associations from a clinical study of cutaneous and
      systemic changes in patients treated with gefitinib and use these to develop and
      characterize a mouse model that recapitulates the human skin rash syndrome caused
      by anti-EGFR therapy. We examined the patients' plasma before and after treatment
      with gefitinib and documented changes in chemokines and leukocyte counts
      associated with the extent of rash or the presence of pruritus. We established a
      parallel mouse model by ablating EGFR in the epidermis. These mice developed skin
      lesions similar to the human rash. Before lesion development, we detected
      increased mRNA expression of chemokines in the skin associated with early
      infiltration of macrophages and mast cells and later infiltration of eosinophils,
      T cells, and neutrophils. As the skin phenotype evolved, changes in blood counts
      and circulating chemokines reproduced those seen in the gefitinib-treated
      patients. Crossing the mutant mice with mice deficient for tumor necrosis factor
      alpha (TNF-alpha) receptors, MyD88, NOS2, CCR2, T cells, or B cells failed to
      reverse the skin phenotype. However, local depletion of macrophages provided
      partial resolution, suggesting that this model can identify targets that may be
      effective in preventing the troublesome and dose-limiting skin response to anti
      EGFR drugs. These results highlight the importance of EGFR signaling in
      maintaining skin immune homeostasis and identify a macrophage contribution to a
      serious adverse consequence of cancer chemotherapy. 

PMID- 23966300
TI  - Epidermal EGFR controls cutaneous host defense and prevents inflammation.
AB  - The epidermal growth factor receptor (EGFR) plays an important role in tissue
      homeostasis and tumor progression. However, cancer patients treated with EGFR
      inhibitors (EGFRIs) frequently develop acneiform skin toxicities, which are a
      strong predictor of a patient's treatment response. We show that the early
      inflammatory infiltrate of the skin rash induced by EGFRI is dominated by
      dendritic cells, macrophages, granulocytes, mast cells, and T cells. EGFRIs
      induce the expression of chemokines (CCL2, CCL5, CCL27, and CXCL14) in epidermal
      keratinocytes and impair the production of antimicrobial peptides and skin
      barrier proteins. Correspondingly, EGFRI-treated keratinocytes facilitate
      lymphocyte recruitment but show a considerably reduced cytotoxic activity against
      Staphylococcus aureus. Mice lacking epidermal EGFR (EGFR(Deltaep)) show a similar
      phenotype, which is accompanied by chemokine-driven skin inflammation, hair
      follicle degeneration, decreased host defense, and deficient skin barrier
      function, as well as early lethality. Skin toxicities were not ameliorated in a
      Rag2-, MyD88-, and CCL2-deficient background or in mice lacking epidermal
      Langerhans cells. The skin phenotype was also not rescued in a hairless (hr/hr)
      background, demonstrating that skin inflammation is not induced by hair follicle
      degeneration. Treatment with mast cell inhibitors reduced the immigration of T
      cells, suggesting that mast cells play a role in the EGFRI-mediated skin
      pathology. Our findings demonstrate that EGFR signaling in keratinocytes
      regulates key factors involved in skin inflammation, barrier function, and innate
      host defense, providing insights into the mechanisms underlying EGFRI-induced
      skin pathologies. 

PMID- 23966301
TI  - Improved rodent maternal metabolism but reduced intrauterine growth after
      vertical sleeve gastrectomy.
AB  - Obesity has profound negative consequences on female reproduction as well as on
      the metabolic health of offspring. Bariatric surgery is the most effective method
      for sustained weight loss. A critical question is whether bariatric surgery can
      reverse the deleterious effects of obesity on both female reproduction and
      subsequent offspring. Vertical sleeve gastrectomy (VSG) is a bariatric procedure
      rapidly growing in popularity because it provides weight loss and other metabolic
      benefits that are comparable to those offered by the more complicated Roux-en-Y
      gastric bypass (RYGB). Female rats rendered obese on a high-fat diet (HFD)
      underwent either VSG or sham surgery. Like their male counterparts, females had
      significant metabolic improvements including reduced adiposity and improved
      glucose tolerance. After VSG, female rats showed a more normal reproductive
      cycle. Despite these maternal benefits, the offspring of dams receiving VSG were
      born smaller and lighter than offspring of control dams that underwent sham
      surgery. When maintained on an HFD after puberty, these adult offspring had a
      greater propensity to develop glucose intolerance and increased adiposity than
      the offspring of lean mothers or obese mothers who underwent sham surgery. These
      data suggest that weight loss alone by obese mothers is not sufficient to reverse
      the deleterious effects of an HFD and obesity on their offspring. 

PMID- 23966302
TI  - Therapeutic intervention of Ebola virus infection in rhesus macaques with the MB
      003 monoclonal antibody cocktail.
AB  - Ebola virus (EBOV) remains one of the most lethal transmissible infections and is
      responsible for high fatality rates and substantial morbidity during sporadic
      outbreaks. With increasing human incursions into endemic regions and the reported
      possibility of airborne transmission, EBOV is a high-priority public health
      threat for which no preventive or therapeutic options are currently available.
      Recent studies have demonstrated that cocktails of monoclonal antibodies are
      effective at preventing morbidity and mortality in nonhuman primates (NHPs) when
      administered as a post-exposure prophylactic within 1 or 2 days of challenge. To
      test whether one of these cocktails (MB-003) demonstrates efficacy as a
      therapeutic (after the onset of symptoms), we challenged NHPs with EBOV and
      initiated treatment upon confirmation of infection according to a diagnostic
      protocol for U.S. Food and Drug Administration Emergency Use Authorization and
      observation of a documented fever. Of the treated animals, 43% survived
      challenge, whereas both the controls and all historical controls with the same
      challenge stock succumbed to infection. These results represent successful
      therapy of EBOV infection in NHPs. 

PMID- 23966303
TI  - Bombesin facilitates GABAergic transmission and depresses epileptiform activity
      in the entorhinal cortex.
AB  - Bombesin and the bombesin-like peptides including neuromedin B (NMB) and gastrin
      releasing peptide (GRP) are important neuromodulators in the brain. We studied
      their effects on GABAergic transmission and epileptiform activity in the
      entorhinal cortex (EC). Bath application of bombesin concentration-dependently
      increased both the frequency and amplitude of sIPSCs recorded from the principal
      neurons in the EC. Application of NMB and GRP exerted the same effects as
      bombesin. Bombesin had no effects on mIPSCs recorded in the presence of TTX but
      slightly depressed the evoked IPSCs. Omission of extracellular Ca(2+) or
      inclusion of voltage-gated Ca(2+) channel blockers, Cd(2+) and Ni(2+), blocked
      bombesin-induced increases in sIPSCs suggesting that bombesin increases GABA
      release via facilitating extracellular Ca(2+) influx. Bombesin induced membrane
      depolarization and slightly increased the input resistance of GABAergic
      interneurons recorded from layer III of the EC. The action potential firing
      frequency of the interneurons was also increased by bombesin. Bombesin-mediated
      depolarization of interneurons was unlikely to be mediated by the opening of a
      cationic conductance but due to the inhibition of inward rectifier K(+) channels.
      Bath application of bombesin, NMB and GRP depressed the frequency of the
      epileptiform activity elicited by deprivation of Mg(2+) from the extracellular
      solution suggesting that bombesin and the bombesin-like peptides have
      antiepileptic effects in the brain.

PMID- 23966304
TI  - The outcome of patients with renal involvement in pediatric-onset systemic lupus
      erythematosus--a 20-year experience in Asia.
AB  - Systemic lupus erythematosus (SLE) predominantly affects women of childbearing
      age, but 15-20% of cases are diagnosed during childhood. It is important for
      physicians to understand the epidemiology and clinical presentation for early
      detection and diagnosis of this disease in difference races. The aim of this
      retrospective review was to provide a 20-year experience for initial clinical and
      laboratory manifestations and outcomes in pediatric-onset SLE (pSLE) in a medical
      center in Asia. We reviewed medical records between April 1990 and June 2012 of
      patients with a diagnosis of International Classification of Diseases, Ninth
      Revision (ICD-9) code 710.0 (SLE), who admitted or received follow-up in the
      Department of Pediatrics at Chang Chung Memorial Hospital. Patients with a
      diagnosis of SLE prior to their 18th birthday and followed up at our hospital
      were eligible for inclusion in this study. Medical records regarding age, gender,
      date of birth and diagnosis, clinical manifestations at diagnosis, laboratory
      results, image studies and the classification criteria were reviewed. Patients
      received regular outpatient department follow-up and laboratory survey every 1-6
      months. The study cohort consisted of 189 patients; 164 females (86.87%) and 25
      males (13.23%). The overall mean age at pSLE diagnosis was 12.62 +/- 2.77 years.
      The most common clinical symptom was malar rash, followed by arthritis and oral
      ulcers. There was no significant difference in clinical and laboratory
      manifestations between females and males. More than half of the patients
      presented with renal involvement initially. The most common histological finding
      was Class IV lupus nephritis (LN), especially in males (p = 0.034) and young age.
      Even with severe LN, the rate of end-stage renal disease (ESRD) was low if
      adequate treatment was initiated. The 5, 10 and 15-year ESRD-free survival rates
      were 95.4%, 94.0% and 89.9% in patients with biopsy-proven LN. However, infection
      was the leading cause of mortality. Therefore, aggressive treatment for major
      organ involvement is important, but physicians must also be aware of fatal
      infection. The overall survival rates were 5 years: 93.4% and 10-20 years: 89.6%.

PMID- 23966305
TI  - Single dose of rituximab for pediatric-onset refractory systemic lupus
      erythematosus.

PMID- 23966306
TI  - Acute coronary syndrome unmasking a puzzling coronary anatomy: role of
      multimodality anatomic and functional imaging.

PMID- 23966307
TI  - Aortic root rupture with giant thoracic haematoma: transient improvement after
      percutaneous closure with ASD-amplatzer device.

PMID- 23966308
TI  - High coronary plaque load: a heavy burden.

PMID- 23966309
TI  - Renal function and outcomes in anticoagulated patients with non-valvular atrial
      fibrillation: the AMADEUS trial.
AB  - AIMS: Limited data are available on the impact of renal function on the outcome
      of patients with atrial fibrillation (AF). METHODS AND RESULTS: AMADEUS was a
      multicentre, randomized, open-label non-inferiority study that compared fixed
      dose idraparinux with conventional anticoagulation by dose-adjusted vitamin K
      antagonists. We performed a post hoc analysis to assess the impact of renal
      function on the outcomes of anticoagulated AF patients. The primary efficacy
      outcome was the composite of stroke/systemic embolism (SE). The principal safety
      outcome of this analysis was major bleeding. We calculated c-indexes, reflecting
      the ability for discriminating diseased vs. non-diseased patients, and the net
      reclassification improvement (NRI, an index of inferior/superior performance of
      risk estimation scores). Of 4576 patients, 45 strokes and 103 major bleeding
      events occurred following an average follow-up of 325 +/- 164 days. Patients with
      CrCl >90 mL/min had an annual stroke/SE rate of 0.6% compared with 0.8% for those
      with CrCl 60-90 mL/min and 2.2% for those with CrCl <60 mL/min (P < 0.001 for
      linear association). After adjusting for stroke risk factors, patients with CrCl
      <60 mL/min had more than two-fold higher risk of stroke/SE and almost 60% higher
      risk of major bleeding compared with those with CrCl >=60. In patients with the
      CHA2DS2VASc score 1-2, CrCl <60 mL/min was associated with eight-fold higher
      stroke risk. When added to the CHA2DS2VASc or CHADS2 scores, CrCl <60 mL/min did
      not improve the c-indexes for CHADS2 (P = 0.054) or CHA2DS2VASc (P = 0.63) but
      resulted in significant NRI (0.26, P = 0.02) in this anticoagulated trial cohort.
      CONCLUSION: Renal impairment (CrCl <60 mL/min) doubles the risk of stroke and
      increased the risk of major bleeding by almost 60% in anticoagulated patients
      with AF. Renal impairment was additive to stroke risk prediction scores based on
      a significant NRI, but no significant improvement in discrimination ability
      (based on c-indexes) for CHA2DS2VASc or CHADS2 was observed.

PMID- 23966310
TI  - Monocyte subset accumulation in the human heart following acute myocardial
      infarction and the role of the spleen as monocyte reservoir.
AB  - AIMS: Monocytes are critical mediators of healing following acute myocardial
      infarction (AMI), making them an interesting target to improve myocardial repair.
      The purpose of this study was a gain of insight into the source and recruitment
      of monocytes following AMI in humans. METHODS AND RESULTS: Post-mortem tissue
      specimens of myocardium, spleen and bone marrow were collected from 28 patients
      who died at different time points after AMI. Twelve patients who died from other
      causes served as controls. The presence and localization of monocytes (CD14(+)
      cells), and their CD14(+)CD16(-) and CD14(+)CD16(+) subsets, were evaluated by
      immunohistochemical and immunofluorescence analyses. CD14(+) cells localized at
      distinct regions of the infarcted myocardium in different phases of healing
      following AMI. In the inflammatory phase after AMI, CD14(+) cells were
      predominantly located in the infarct border zone, adjacent to cardiomyocytes, and
      consisted for 85% (78-92%) of CD14(+)CD16(-) cells. In contrast, in the
      subsequent post-AMI proliferative phase, massive accumulation of CD14(+) cells
      was observed in the infarct core, containing comparable proportions of both the
      CD14(+)CD16(-) [60% (31-67%)] and CD14(+)CD16(+) subsets [40% (33-69%)].
      Importantly, in AMI patients, of the number of CD14(+) cells was decreased by 39%
      in the bone marrow and by 58% in the spleen, in comparison with control patients
      (P = 0.02 and <0.001, respectively). CONCLUSIONS: Overall, this study showed a
      unique spatiotemporal pattern of monocyte accumulation in the human myocardium
      following AMI that coincides with a marked depletion of monocytes from the
      spleen, suggesting that the human spleen contains an important reservoir function
      for monocytes.

PMID- 23966311
TI  - Stabilization of atherosclerotic plaques: an update.

PMID- 23966313
TI  - Autologous solution protects bovine cartilage explants from IL-1alpha- and
      TNFalpha-induced cartilage degradation.
AB  - Osteoarthritis (OA) is characterized by deterioration of articular cartilage
      driven by an imbalance of pro- and anti-inflammatory cytokines. To address the
      cartilage deterioration observed in OA, an autologous protein solution (APS) has
      been developed which has been shown to inhibit the production of destructive
      proteases and inflammatory cytokines from chondrocytes and monocytes,
      respectively. The purpose of this study was to determine the chondroprotective
      effect of APS on IL-1alpha- or TNFalpha-challenged bovine articular cartilage
      explants. Cartilage explants were cultured in the presence or absence of
      recombinant inflammatory cytokines, IL-1alpha and TNFalpha. Explants under
      equivalent inflammatory conditions were pretreated with recombinant antagonists
      IL-1ra, sTNF-RI, or APS to measure their inhibition of matrix degradation.
      Explants were further evaluated with Safranin-O, Masson's Trichrome, and
      Hematoxylin and Eosin histological staining. APS was more effective than
      recombinant antagonists in preventing cartilage matrix degradation and inhibited
      any measurable IL-1alpha-induced collagen release over a 21-day culture period.
      APS treatment reduced the degree of Safranin-O staining loss when cartilage
      explants were cultured with IL-1alpha or TNFalpha. Micrographs of APS treated
      cartilage explants showed an increase in observed cellularity and apparent cell
      division. APS may have the potential to prevent cartilage loss associated with
      early OA.

PMID- 23966312
TI  - Antihypertensive efficacy of angiotensin receptor blockers as monotherapy as
      evaluated by ambulatory blood pressure monitoring: a meta-analysis.
AB  - AIMS: Angiotensin receptor blockers (ARBs) are available in different dosages and
      it is common clinical practice to uptitrate if blood pressure goal is not
      achieved with the initial dose. Data on the incremental antihypertensive efficacy
      with uptitration are scarce. It is also unclear if antihypertensive efficacy of
      losartan is comparable with other ARBs. METHODS AND RESULTS: We systematically
      reviewed PubMed/EMBASE/Cochrane databases for all randomized clinical trials
      until December 2012 reporting 24 h ambulatory blood pressure (ABP) for most
      commonly available ARBs in patients with hypertension. Reduction in ABP with ARBs
      was evaluated at 25% of the maximum (max) dose, 50% of the max dose, and at the
      max dose. Comparison was made between 24 h BP-lowering effect of losartan 50 and
      100 mg and other ARBs at 50% max dose and the max dose, respectively. Sixty-two
      studies enrolling 15 289 patients (mean age 56 years; 60% men) with a mean
      duration of 10 weeks were included in the analysis. Overall, the dose-response
      curve with ARBs was shallow with decrease of 10.3/6.7 (systolic/diastolic),
      11.7/7.6, and 13.0/8.3 mmHg with 25% max dose, 50% max dose, and with the max
      dose of ARBs, respectively. Losartan in the dose of 50 mg lowered ABP less well
      than other ARBs at 50% max dose by 2.5 mmHg systolic (P < 0.0001) and 1.8 mmHg
      diastolic (P = 0.0003). Losartan 100 mg lowered ABP less well than other ARBs at
      max dose by 3.9 mm Hg systolic (P = 0.0002) and 2.2 mmHg diastolic (P = 0.002).
      CONCLUSION: In this comprehensive analysis of the antihypertensive efficacy of
      ARBs by 24 h ABP, we observed a shallow dose-response curve, and uptitration
      marginally enhanced the antihypertensive efficacy. Blood pressure reduction with
      losartan at starting dose and at max dose was consistently inferior to the other
      ARBs.

PMID- 23966314
TI  - Subchronic toxicity evaluation of anthraquinone in Fischer 344 rats.
AB  - Female F344 rats were exposed to anthraquinone (AQ) by dietary feed at
      concentrations of 0, 50, 150, 469, 938, 1875, or 3750 ppm for 2 or 13 weeks. End
      points evaluated included clinical observations, body weights, serum chemistry,
      blood AQ, gross pathology, organ weights, and select tissue histopathology. Mean
      body weight and food consumption were 5% to 10% lower than control values in rats
      of the >=938 ppm group during study weeks 2 through 13. Occasional decreases in
      body weight means were also observed in rats of the 150 and 469 ppm groups.
      Increases in liver, kidney, and spleen weights were observed in rats exposed to
      AQ diet concentrations >=150 ppm for 13 weeks. Urinary bladder weights were
      increased at >=469 ppm. Liver and spleen weights were also increased following 2
      weeks of exposure. Liver weight increases were clearly dependent on AQ
      concentration. At 2 weeks, decreases in serum aspartate aminotransferase (AST),
      blood urea nitrogen, and creatinine concentrations were observed in higher AQ
      exposure groups, and AST was decreased at 13 weeks (>=1875 ppm). Microscopic
      alterations were observed in the liver (mild centrilobular hypertrophy), spleen
      (mild hematopoietic cell proliferation and pigmentation), and kidneys (minimal
      hyaline droplets) of rats exposed to AQ for 13 weeks. Blood AQ concentrations
      ranged from 0.75 to 14.8 ug/mL in rats of the 150 to 3750 ppm groups,
      respectively, and were similar in value following either 2 weeks or 13 weeks of
      exposure. A no observed adverse effect level of 469 ppm AQ (31.3 mg/kg/d) was
      selected based on the absence of liver histopathology. 

PMID- 23966315
TI  - Satellite observed widespread decline in Mongolian grasslands largely due to
      overgrazing.
AB  - The Mongolian Steppe is one of the largest remaining grassland ecosystems. Recent
      studies have reported widespread decline of vegetation across the steppe and
      about 70% of this ecosystem is now considered degraded. Among the scientific
      community there has been an active debate about whether the observed degradation
      is related to climate, or over-grazing, or both. Here, we employ a new
      atmospheric correction and cloud screening algorithm (MAIAC) to investigate
      trends in satellite observed vegetation phenology. We relate these trends to
      changes in climate and domestic animal populations. A series of harmonic
      functions is fitted to Moderate Resolution Imaging Spectroradiometer (MODIS)
      observed phenological curves to quantify seasonal and inter-annual changes in
      vegetation. Our results show a widespread decline (of about 12% on average) in
      MODIS observed normalized difference vegetation index (NDVI) across the country
      but particularly in the transition zone between grassland and the Gobi desert,
      where recent decline was as much as 40% below the 2002 mean NDVI. While we found
      considerable regional differences in the causes of landscape degradation, about
      80% of the decline in NDVI could be attributed to increase in livestock. Changes
      in precipitation were able to explain about 30% of degradation across the country
      as a whole but up to 50% in areas with denser vegetation cover (P < 0.05).
      Temperature changes, while significant, played only a minor role (r(2)  = 0.10, P
      < 0.05). Our results suggest that the cumulative effect of overgrazing is a
      primary contributor to the degradation of the Mongolian steppe and is at least
      partially responsible for desertification reported in previous studies. 

PMID- 23966316
TI  - Various polar tripeptides as asymmetric organocatalyst in direct aldol reactions
      in aqueous media.
AB  - A series of tripeptide organocatalysts containing a secondary amine group and two
      amino acids with polar side chain units were developed and evaluated in the
      direct asymmetric intermolecular aldol reaction of 4-nitrobenzaldehyde and
      cyclohexanone. The effectiveness of short polar peptides as asymmetric catalysts
      in aldol reactions to attain high yields of enantio- and diastereoselective
      isomers were investigated. In a comparison, glutamic acid and histidine produced
      higher % ee and yields when they were applied as the second amino acid in short
      trimeric peptides. These short polar peptides were found to be efficient
      organocatalysts for the asymmetric aldol addition reaction in aqueous media.

PMID- 23966317
TI  - Antitumor efficacy of doxorubicin-loaded laponite/alginate hybrid hydrogels.
AB  - Degradable hybrid hydrogels with improved stability are prepared by incorporating
      nanodisks of biocompatible laponite (LP) in alginate (AG) hydrogels using Ca(2+)
      as a crosslinker. The Dox-loaded hybrid hydrogels give a controlled Dox release
      at physiological environment in a sustained manner. Under conditions that mimic
      the tumor environment, both the sustainability in the Dox release (up to 17 d)
      and the release efficiency from LP/AG-Dox hydrogels are improved. The in situ
      degradation of these hybrid hydrogels gives rise to nanohybrids that might serve
      as vehicles for carrying Dox through the cell membrane and diminish the effect of
      Dox ion-trapping in the acidic extracellular environment of the tumor and/or in
      the endo-lysosomal cell compartments. 

PMID- 23966318
TI  - Rapid movement of water and cryoprotectants in pig expanded blastocysts via
      channel processes: its relevance to their higher tolerance to cryopreservation.
AB  - Pig oocytes and embryos are highly sensitive to cryopreservation; however,
      tolerance to cryopreservation increases in embryos at the expanded blastocyst
      stage. This increased tolerance may be attributed to a decrease in cytoplasmic
      lipid droplets at this stage. We previously showed that an increase in the
      permeability of the plasma membrane in mouse oocytes to water and
      cryoprotectants, caused by the artificial expression of aquaporin 3, an
      aquaglyceroporin, enhanced tolerance to cryopreservation. In the present study,
      we investigated whether membrane permeability was also involved in the tolerance
      of pig embryos to cryopreservation. The permeability of oocytes and morulae to
      water and glycerol was low, whereas that of expanded blastocysts was high.
      Activation energy for permeability to water, glycerol, ethylene glycol, and
      dimethyl sulfoxide was markedly lower for expanded blastocysts than for oocytes.
      This suggests that water and these cryoprotectants move through expanded
      blastocysts predominantly by facilitated diffusion and through oocytes
      predominantly by simple diffusion. Aquaporin 3 mRNA was expressed in expanded
      blastocysts abundantly, but less so in oocytes. On the other hand, the
      permeability of expanded blastocysts to propylene glycol was as low as that of
      oocytes, and activation energy for its permeability was similar to that of
      oocytes, which suggests that propylene glycol moves through oocytes and embryos
      predominantly by simple diffusion. These results suggest that the higher
      tolerance of pig expanded blastocysts to cryopreservation is also related to high
      membrane permeability due to the expression of water/cryoprotectant channels, in
      addition to the decrease in cytoplasmic lipid droplets. 

PMID- 23966319
TI  - The ERK1/2 signaling pathway regulates 11beta-hydroxysteroid dehydrogenase type 2
      expression in human trophoblast cells through a transcriptional mechanism.
AB  - The placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2; encoded by
      the HSD11B2 gene) plays a key role in fetal development, but its regulation is
      incompletely understood. We previously demonstrated that p38 MAPK was a positive
      regulator of placental 11beta-HSD2. However, it remains unknown if the other two
      MAPKs, ERK1/2 and JNK, were also involved. In the present study, we identified
      ERK1/2 as an important regulator of placental 11beta-HSD2. We showed that
      inhibition of ERK1/2 with the pharmacological inhibitor U0126 led to a 3-fold
      increase in 11beta-HSD2 activity, protein, and mRNA in primary human placental
      trophoblast cells. In contrast, the JNK inhibitor SP600125 had no effect.
      Furthermore, U0126 increased the HSD11B2 promoter activity by 300%, indicating
      that ERK1/2 regulates placental 11beta-HSD2 expression through a transcriptional
      mechanism. Importantly, siRNA-mediated knockdown of ERK1/2 caused a similar
      increase in 11beta-HSD2 protein. In addition, given that we previously showed
      that cadmium reduced placental 11beta-HSD2 expression via a transcriptional
      mechanism, but the signal transduction pathways involved remain unclear, we also
      addressed this question and found that treatment of trophoblast cells with
      cadmium led to rapid activation of ERK1/2. Importantly, U0126 completely
      abrogated the inhibitory effects of cadmium on placental 11beta-HSD2. Taken
      together, the present study not only identifies the ERK1/2 signaling pathway as a
      potent negative regulator of placental 11beta-HSD2 but also demonstrates that
      this pathway mediates cadmium repression of placental 11beta-HSD2. Thus, our
      present study reveals 11beta-HSD2 as an important target through which ERK1/2 may
      regulate human placental function and consequently fetal development.

PMID- 23966320
TI  - Recent insights into spindle function in mammalian oocytes and early embryos.
AB  - Errors in chromosome segregation in oocytes and early embryos lead to embryo
      aneuploidy, which contributes to early pregnancy loss. At the heart of chromosome
      segregation is the spindle, a dynamic biomechanical machine fashioned from
      microtubules, which is tasked with gathering and sorting chromosomes and
      dispatching them to the daughter cells at the time of cell division.
      Understanding the causes of segregation error in the oocyte and early embryo will
      undoubtedly hinge on a thorough understanding of the mechanism of spindle
      assembly and function in these highly specialized cellular environments. The
      recent advent of live imaging approaches to observe chromosome segregation in
      real-time in oocytes and embryos, paired with gene-silencing techniques and
      specific inhibition for assessing the function of a protein of interest, has led
      to a substantial advance in our understanding of chromosome segregation in early
      mammalian development. These studies have uncovered numerous mechanistic
      differences between oocytes, embryos, and traditional model systems. In addition,
      a flurry of recent studies using naturally aged mice as the model for human aging
      have begun to shed light on the increased levels of aneuploidy seen in embryos
      from older mothers. Here we review these recent developments and consider what
      has been learned about the causes of chromosome missegregation in early
      development. 

PMID- 23966322
TI  - Misregulated progesterone secretion and impaired pregnancy in Cyp11a1 transgenic
      mice.
AB  - Normal pregnancy is supported by increased levels of progesterone (P4), which is
      secreted from ovarian luteal cells via enzymatic steps catalyzed by P450scc
      (CYP11A1) and HSD3B. The development and maintenance of corpora lutea during
      pregnancy, however, are less well understood. Here we used Cyp11a1 transgenic
      mice to delineate the steps of luteal cell differentiation during pregnancy.
      Cyp11a1 in a bacterial artificial chromosome was injected into mouse embryos to
      generate transgenic mice with transgene expression that recapitulated endogenous
      Cyp11a1 expression. Cyp11a1 transgenic females displayed reduced pregnancy rate,
      impaired implantation and placentation, and decreased litter size in utero,
      although they produced comparable numbers of blastocysts. The differentiation of
      transgenic luteal cells was delayed during early pregnancy as shown by the
      delayed activation of genes involved in steroidogenesis and cholesterol
      availability. Luteal cell mitochondria were elongated, and their numbers were
      reduced, with morphology and numbers similar to those observed in granulosa
      cells. Transgenic luteal cells accumulated lipid droplets and secreted less
      progesterone during early pregnancy. The progesterone level returned to normal on
      gestation day 9 but was not properly withdrawn at term, leading to delayed
      stillbirth. P4 supplementation rescued the implantation rates but not the ovarian
      defects. Thus, overexpression of Cyp11a1 disrupts normal development of the
      corpus luteum, leading to progesterone insufficiency during early pregnancy.
      Misregulation of the progesterone production in Cyp11a1 transgenic mice during
      pregnancy resulted in aberrant implantation, anomalous placentation, and delayed
      parturition.

PMID- 23966321
TI  - Cyclooxygenase-1 inhibition prolongs postnatal ovarian follicle lifespan in mice.
AB  - Menopause is the permanent cessation of menstruation that results from depletion
      of ovarian germ cells and follicles. Although most animals experience
      reproductive senescence, the mechanisms differ from that in women, who may live
      more than one-third of their lives after menopause and consequently face the risk
      of a number of menopause-associated health problems. Understanding factors that
      influence ovarian aging may provide strategies to delay or alleviate
      physiological alterations that take place in postmenopausal women. The germ cell
      deficient Wv mice recapitulate follicle loss, prolong postreproductive lifespan,
      and model many physiological changes that take place in postmenopausal women.
      Here, using genetic and pharmacological approaches, we found that inhibition of
      cyclooxygenase-1 but not cyclooxygenase-2 in Wv mice delays germ cell depletion
      and preserves ovarian follicles. Cyclooxygenase-1 inhibition slows down follicle
      maturation at the conversion of primary to secondary follicles and prolongs
      postnatal ovarian follicle lifespan. The current study suggests that inhibition
      of cyclooxygenase-1 may be able to delay ovarian aging and modulate menopausal
      timing. 

PMID- 23966323
TI  - Potential new mechanisms of placental damage in celiac disease: anti
      transglutaminase antibodies impair human endometrial angiogenesis.
AB  - Celiac disease (CD) is an autoimmune enteropathy triggered by gluten ingestion
      and characterized by circulating anti-transglutaminase type 2 (anti-TG2)
      autoantibodies. An epidemiological link between maternal CD and increased risk of
      pregnancy failure has been established; however, the mechanism underlying this
      association is still poorly understood. Because proper endometrial angiogenesis
      and decidualization are prerequisites for placental development, we investigated
      the effect of anti-TG2 antibodies on the process of endometrial angiogenesis.
      Binding of anti-TG2 antibodies to human endometrial endothelial cells (HEECs) was
      evaluated by ELISA. Angiogenesis was studied in vitro on HEECs and in vivo in a
      murine model. In particular, we investigated the effect of anti-TG2 antibodies on
      HEEC matrix metalloprotease-2 (MMP-2) activity by gelatin zymography,
      cytoskeletal organization and membrane properties by confocal microscopy, and
      activation of extracellular signal-regulated kinases (ERKs) and focal adhesion
      kinase (FAK) by Western blot analysis. Anti-TG2 antibodies bound to HEECs and
      decreased newly formed vessels both in vitro and in vivo. Anti-TG2 antibodies
      impaired angiogenesis by inhibiting the activation of MMP-2, disarranging
      cytoskeleton fibers, changing the physical and mechanical properties of cell
      membranes, and inhibiting the intracellular phosphorylation of FAK and ERK. Anti
      TG2 antibodies inhibit endometrial angiogenesis affecting the TG2-dependent
      migration of HEECs and extracellular matrix degradation, which are necessary to
      form new vessels. Our results identify pathogenic mechanisms of placental damage
      in CD. 

PMID- 23966324
TI  - A promoter fragment of the sycp1 gene is sufficient to drive transgene expression
      in male and female meiotic germ cells in zebrafish.
AB  - The synaptonemal complex protein 1 (Sycp1) is required for the formation of
      crossovers that occurs during the meiotic prophase. The tissue and cell-specific
      expression pattern of the Sycp1 protein have been studied in mammals and fish,
      but data on the corresponding transcript remain scarce. In this report, we
      described for the first time in zebrafish the tissue- and cell-specific
      expression pattern of the sycp1 gene. In ovary, the expression of the sycp1
      transcript was restricted to the early primary oocytes. In testis, the sycp1
      transcript was observed in primary spermatocytes in agreement with a previous
      report describing the localization of the Sycp1 protein in those cells.
      Unexpectedly, sycp1 transcript expression remained high in spermatids. To gain
      insight on the genomic region responsible for the sycp1 gene expression pattern,
      we generated four independent Dr_sycp1:eGFP transgenic zebrafish lines carrying
      the -1482/+338 gene fragment fused to the enhanced green fluorescent protein
      reporter gene. We demonstrate that this promoter fragment contains the
      information required for the cell-specific expression of the endogenous sycp1
      gene in males and in females. However, the GFP protein and its associated
      fluorescence persist in spermatozoa and maturing oocytes. The Dr_sycp1:eGFP
      zebrafish lines have the potential to be valuable models to trace meiosis onset
      in zebrafish and constitute the first transgenic lines expressing the GFP
      reporter protein only in the male meiotic and postmeiotic cells in fish. 

PMID- 23966325
TI  - Prenatal testosterone induces sex-specific dysfunction in endothelium-dependent
      relaxation pathways in adult male and female rats.
AB  - Prenatal testosterone (T) exposure impacts postnatal cardiovascular function,
      leading to increases in blood pressure with associated decreased endothelium
      dependent vascular relaxation in adult females. Endothelial function in males is
      not known. Furthermore, which of the endothelial pathways contributes to
      endothelial dysfunction and if there exists sex differences are not known. The
      objective of this study was to characterize the relative contribution of nitric
      oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) to the impaired
      endothelium-dependent vasodilation in prenatal T-exposed adult males and females.
      Offspring of pregnant rats treated with T propionate or its vehicle were
      examined. Telemetric blood pressure levels and endothelium-dependent vascular
      reactivity were assessed with wire myography. Levels of nitric oxide synthase
      (NOS3) and Kcnn3 and Kcnn4 channel expression were examined in mesenteric
      arteries. Mean arterial pressure was significantly higher in T males and females
      than in controls. Endothelium-dependent acetylcholine relaxation was
      significantly lower in both T males and females. EDHF-mediated relaxation was
      specifically blunted in T males (Emax = 48.64% +/- 3.73%) compared to that in
      control males (Emax = 81.71% +/- 3.18%); however, NO-mediated relaxation was
      specifically impaired in T females (Emax = 36.01% +/- 4.29%) compared with that
      in control females (Emax = 54.56% +/- 6.37%). Relaxation to sodium nitroprusside
      and levcromakalim were unaffected with T-treatment. NOS3 protein was decreased in
      T females but not in T males. Kcnn3 expression was decreased in both T males and
      females compared to controls. These findings suggest that prenatal T leads to an
      increase in blood pressure in the adult offspring, associated with blunting of
      endothelial cell-associated relaxation and that the effects are sex-specific:
      EDHF-related in males and NO-related in females. 

PMID- 23966326
TI  - Adrenomedullin increased the short-circuit current in the pig oviduct through
      chloride channels via the CGRP receptor: mediation by cAMP and calcium ions but
      not by nitric oxide.
AB  - The oviduct serves as a site for the fertilization of the ovum and the transport
      of the conceptus down to the uterus for implantation. In this study, we
      investigated the presence of adrenomedullin (ADM) and its receptor component
      proteins in the pig oviduct. The effect of ADM on oviductal secretion, the
      specific receptor, and the mechanisms involved were also investigated. The
      presence of ADM and its receptor component proteins in the pig oviduct were
      confirmed using immunostaining. Short-circuit current (I(sc)) technique was
      employed to study chloride ion secretion in the oviductal epithelium. ADM
      increased I(sc) through cAMP- and calcium-activated chloride channels, and this
      effect could be inhibited by the CGRP receptor antagonist, hCGRP8-37. In
      contrast, the nitric oxide synthase inhibitor, L-NG-nitroarginine methyl ester (L
      NAME), could not block the effect of ADM on I(sc). In summary, ADM may increase
      oviductal fluid secretion via chloride secretion independent of the nitric oxide
      pathway for the transport of sperm and the conceptus.

PMID- 23966327
TI  - Metabolite profile analysis reveals functional effects of 28-day vitamin B-6
      restriction on one-carbon metabolism and tryptophan catabolic pathways in healthy
      men and women.
AB  - Suboptimal vitamin B-6 status, as reflected by low plasma pyridoxal 5'-phosphate
      (PLP) concentration, is associated with increased risk of vascular disease. PLP
      plays many roles, including in one-carbon metabolism for the acquisition and
      transfer of carbon units and in the transsulfuration pathway. PLP also serves as
      a coenzyme in the catabolism of tryptophan. We hypothesize that the pattern of
      these metabolites can provide information reflecting the functional impact of
      marginal vitamin B-6 deficiency. We report here the concentration of major
      constituents of one-carbon metabolic processes and the tryptophan catabolic
      pathway in plasma from 23 healthy men and women before and after a 28-d
      controlled dietary vitamin B-6 restriction (<0.35 mg/d). liquid chromatography
      tandem mass spectrometry analysis of the compounds relevant to one-carbon
      metabolism showed that vitamin B-6 restriction yielded increased cystathionine
      (53% pre- and 76% postprandial; P < 0.0001) and serine (12% preprandial; P <
      0.05), and lower creatine (40% pre- and postprandial; P < 0.0001), creatinine (9%
      postprandial; P < 0.05), and dimethylglycine (16% postprandial; P < 0.05)
      relative to the vitamin B-6-adequate state. In the tryptophan pathway, vitamin B
      6 restriction yielded lower kynurenic acid (22% pre- and 20% postprandial; P <
      0.01) and higher 3-hydroxykynurenine (39% pre- and 34% postprandial; P < 0.01).
      Multivariate ANOVA analysis showed a significant global effect of vitamin B-6
      restriction and multilevel partial least squares-discriminant analysis supported
      this conclusion. Thus, plasma concentrations of creatine, cystathionine,
      kynurenic acid, and 3-hydroxykynurenine jointly reveal effects of vitamin B-6
      restriction on the profiles of one-carbon and tryptophan metabolites and serve as
      biomarkers of functional effects of marginal vitamin B-6 deficiency. 

PMID- 23966329
TI  - A health promotion intervention can affect diet quality in early childhood.
AB  - Initiatives to promote children's nutrition and prevent childhood obesity are
      vital. Dietary patterns are a useful way to characterize whole diets, though no
      previous early childhood health promotion trial to our knowledge has assessed
      intervention impact using this approach. This research aimed to assess the effect
      of a healthy eating and physical activity intervention on young children's
      dietary patterns. The Melbourne Infant Feeding Activity and Nutrition Trial
      Program was a health promotion, cluster-randomized controlled trial involving 542
      families. Child diets were assessed by multiple 24-h recalls postintervention at
      ~18 mo of age. An Obesity Protective Dietary Index (OPDI) was created and dietary
      patterns were also assessed by principal components analysis (PCA). These
      outcomes were used to compare intervention and control participants to test the
      effectiveness of the intervention. Children in the intervention arm scored higher
      (15.6 +/- 5.9) than those in the control arm (14.5 +/- 6.7) for the OPDI (scores
      out of 30, P = 0.01). Three dietary patterns were identified by PCA; however, the
      scores did not substantially differ between the intervention and control arms. In
      conclusion, this paper presents novel results in both the evaluation of an early
      childhood health promotion intervention and the assessment of child dietary
      patterns. The results highlight the capacity for such an initiative to improve
      child diets and the need for further research in this area. 

PMID- 23966328
TI  - Low-fat milk ingestion prevents postprandial hyperglycemia-mediated impairments
      in vascular endothelial function in obese individuals with metabolic syndrome.
AB  - Greater intakes of low-fat dairy foods are associated with a lower risk of
      cardiovascular disease. The objective of this study was to examine whether acute
      low-fat milk ingestion would limit postprandial impairments in vascular
      endothelial function by limiting oxidative stress responses that decrease nitric
      oxide (NO) bioavailability. A randomized, double-blind, cross-over study was
      conducted in adults with metabolic syndrome (MetS) who ingested low-fat milk (475
      mL) or an isocaloric volume of rice milk after an overnight fast. Brachial artery
      flow-mediated dilation (FMD), plasma glucose, malondialdehyde (MDA), arginine
      (ARG), and asymmetric dimethylarginine (ADMA) were assessed at 30-min intervals
      during the 3-h postprandial period. Participants' (n = 19) postprandial FMD
      responses were unaffected by low-fat milk but transiently decreased (P < 0.01)
      from 6.2 +/- 0.8% (mean +/- SEM) at baseline to 3.3 +/- 0.7% at 30 min and 3.9 +/
      0.6% at 60 min following rice milk consumption. Glucose and MDA increased to a
      greater extent in the rice milk trial (P < 0.001). The MDA area under the 3 h
      postprandial curve (AUC0-3 h) was correlated with glucose AUC0-3 h (r = 0.75; P <
      0.01) and inversely related to FMD AUC0-3 h (r = -0.59; P < 0.01). ARG decreased
      following rice milk and increased with low-fat milk, whereas only rice milk
      increased ADMA:ARG. The ADMA:ARG AUC0-3 h was correlated with MDA AUC0-3 h (r =
      0.55) and was inversely related to FMD AUC0-3 h (r = -0.52) (P < 0.05). These
      findings suggest that low-fat milk maintains vascular endothelial function in
      individuals with MetS by limiting postprandial hyperglycemia that otherwise
      increases lipid peroxidation and reduces NO bioavailability. This trial was
      registered at clinicaltrials.gov as NCT01411293. 

PMID- 23966330
TI  - Vitamin D regulates the gut microbiome and protects mice from dextran sodium
      sulfate-induced colitis.
AB  - The active form of vitamin D [1,25-dihydroxycholecalciferol, 1,25(OH)2D3] and the
      vitamin D receptor (VDR) regulate susceptibility to experimental colitis. The
      effect of the bacterial microflora on the susceptibility of C57BL/6 mice to
      dextran sodium sulfate-induced colitis was determined. Mice that cannot produce
      1,25(OH)2D3 [Cyp27b1 (Cyp) knockout (KO)], VDR KO as well as their wild-type
      littermates were used. Cyp KO and VDR KO mice had more bacteria from the
      Bacteroidetes and Proteobacteria phyla and fewer bacteria from the Firmicutes and
      Deferribacteres phyla in the feces compared with wild-type. In particular, there
      were more beneficial bacteria, including the Lactobacillaceae and Lachnospiraceae
      families, in feces from Cyp KO and VDR KO mice than in feces from wild-type.
      Helicobacteraceae family member numbers were elevated in Cyp KO compared with
      wild-type mice. Depletion of the gut bacterial flora using antibiotics protected
      mice from colitis. 1,25(OH)2D3 treatment (1.25 MUg/100 g diet) of Cyp KO mice
      decreased colitis severity and reduced the numbers of Helicobacteraceae in the
      feces compared with the numbers in the feces of untreated Cyp KO mice. The
      mechanisms by which the dysbiosis occurs in VDR KO and Cyp KO mice included lower
      expression of E-cadherin on gut epithelial and immune cells and fewer tolerogenic
      dendritic cells that resulted in more gut inflammation in VDR and Cyp KO mice
      compared with wild-type mice. Increased host inflammation has been shown to
      provide pathogens with substrates to out-compete more beneficial bacterial
      species. Our data demonstrate that vitamin D regulates the gut microbiome and
      that 1,25(OH)2D3 or VDR deficiency results in dysbiosis, leading to greater
      susceptibility to injury in the gut. 

PMID- 23966331
TI  - The plasma proteome identifies expected and novel proteins correlated with
      micronutrient status in undernourished Nepalese children.
AB  - Micronutrient deficiencies are common in undernourished societies yet remain
      inadequately assessed due to the complexity and costs of existing assays. A
      plasma proteomics-based approach holds promise in quantifying multiple
      nutrient:protein associations that reflect biological function and nutritional
      status. To validate this concept, in plasma samples of a cohort of 500 6- to 8-y
      old Nepalese children, we estimated cross-sectional correlations between vitamins
      A (retinol), D (25-hydroxyvitamin D), and E (alpha-tocopherol), copper, and
      selenium, measured by conventional assays, and relative abundance of their major
      plasma-bound proteins, measured by quantitative proteomics using 8-plex iTRAQ
      mass tags. The prevalence of low-to-deficient status was 8.8% (<0.70 MUmol/L) for
      retinol, 19.2% (<50 nmol/L) for 25-hydroxyvitamin D, 17.6% (<9.3 MUmol/L) for
      alpha-tocopherol, 0% (<10 MUmol/L) for copper, and 13.6% (<0.6 MUmol/L) for
      selenium. We identified 4705 proteins, 982 in >50 children. Employing a linear
      mixed effects model, we observed the following correlations: retinol:retinol
      binding protein 4 (r = 0.88), 25-hydroxyvitamin D:vitamin D-binding protein (r =
      0.58), alpha-tocopherol:apolipoprotein C-III (r = 0.64), copper:ceruloplasmin (r
      = 0.65), and selenium:selenoprotein P isoform 1 (r = 0.79) (all P < 0.0001),
      passing a false discovery rate threshold of 1% (based on P value-derived q
      values). Individual proteins explained 34-77% (R(2)) of variation in their
      respective nutrient concentration. Adding second proteins to models raised R(2)
      to 48-79%, demonstrating a potential to explain additional variation in nutrient
      concentration by this strategy. Plasma proteomics can identify and quantify
      protein biomarkers of micronutrient status in undernourished children. The
      maternal micronutrient supplementation trial, from which data were derived as a
      follow-up activity, was registered at clinicaltrials.gov as NCT00115271. 

PMID- 23966334
TI  - Threat to the point: improving the value of comparative extinction risk analysis
      for conservation action.
AB  - Comparative extinction risk analysis is a common approach for assessing the
      relative plight of biodiversity and making conservation recommendations. However,
      the usefulness of such analyses for conservation practice has been questioned.
      One reason for underperformance may be that threats arising from global
      environmental changes (e.g., habitat loss, invasive species, climate change) are
      often overlooked, despite being widely regarded as proximal drivers of species'
      endangerment. We explore this problem by (i) reviewing the use of threats in this
      field and (ii) quantitatively investigating the effects of threat exclusion on
      the interpretation and potential application of extinction risk model results. We
      show that threat variables are routinely (59%) identified as significant
      predictors of extinction risk, yet while most studies (78%) include extrinsic
      factors of some kind (e.g., geographic or bioclimatic information), the majority
      (63%) do not include threats. Despite low overall usage, studies are increasingly
      employing threats to explain patterns of extinction risk. However, most continue
      to employ methods developed for the analysis of heritable traits (e.g., body
      size, fecundity), which may be poorly suited to the treatment of nonheritable
      predictors including threats. In our global mammal and continental amphibian
      extinction risk case studies, omitting threats reduced model predictive
      performance, but more importantly (i) reduced mechanistic information relevant to
      management; (ii) resulted in considerable disagreement in species classifications
      (12% and 5% for amphibians and mammals, respectively, translating to dozens and
      hundreds of species); and (iii) caused even greater disagreement (20-60%) in a
      downstream conservation application (species ranking). We conclude that the use
      of threats in comparative extinction risk analysis is important and increasing
      but currently in the early stages of development. Priorities for future studies
      include improving uptake, availability, quality and quantification of threat
      data, and developing analytical methods that yield more robust, relevant and
      tangible products for conservation applications. 

PMID- 23966332
TI  - p21Cip restrains hippocampal neurogenesis and protects neuronal progenitors from
      apoptosis during acute systemic inflammation.
AB  - Altered neurogenesis in adult hippocampus is implicated in cognition impairment
      and depression. Inflammation is a potent inhibitor of neurogenesis. The cyclin
      dependent kinase inhibitor p21(Cip1) (p21) restrains cell cycle progression and
      arrests the cell in the G1 phase. We recently showed that p21 is expressed in
      neuronal progenitors and regulates proliferation of these cells in the
      subgranular zone of the dentate gyrus of hippocampus where adult neurogenesis
      occurs. The current study suggests that p21 is induced in vivo in the hippocampus
      of WT mice in response to acute systemic inflammation caused by LPS injections,
      restrains neuronal progenitor proliferation and protects these cells from
      inflammation-induced apoptosis. In intact p21-/- hippocampus, neuronal
      progenitors proliferate more actively as assessed by BrdU incorporation, and give
      rise to increased number of DCX positive neuroblasts. However, when mice were
      treated with LPS, the number of neuroblasts decreased due to induced subgranular
      zone apoptosis. In vitro, differentiating Tuj-1 positive neuroblasts isolated
      from p21-/- hippocampus exhibited increased proliferation rate, measured by Ki-67
      staining, as compared to WT cells (p<0.05). In WT neuronal progenitors treated
      with IL-6, the number of p21-positive cells was increased (p<0.05), and this led
      to Tuj-1(+) cell proliferation restraint, whereas the number of proliferating
      GFAP(+) astrocytes was increased ~ 2-fold. Thus, when p21 is intact, inflammation
      might divert neuronal progenitors towards astrogliogenesis by inducing p21. At
      the same time, when p21 is lacking, no effects of IL-6 on proliferation of Tuj
      1(+) cells or GFAP(+) cells are detected in differentiating p21-/- neuronal
      progenitors. These results underscore the important role of p21 controlling
      hippocampal neuronal differentiation during inflammation.

PMID- 23966333
TI  - Effects of ACL reconstruction surgery on muscle activity of the lower limb during
      a jump-cut maneuver in males and females.
AB  - We compared muscle activity of the quadriceps, hamstring, and gastrocnemius
      muscles when ACL-intact (ACL(INT)) and ACL-reconstructed (ACL(REC)) male and
      female subjects performed a jump-cut task. Surface electromyography sensors were
      used to evaluate time to peak muscle activity and muscle activity ratios. Rectus
      femoris (RF) and vastus medialis (VM) peak timing was 71 and 78 ms earlier in
      ACL(INT) than in ACL(REC) subjects, respectively. Biceps femoris (BF) peak timing
      was 90 ms earlier in ACL(INT) than in ACL(REC) subjects and 75 ms earlier in
      females than in males. Medial gastrocnemius (MG) muscle peak timing was 77 ms
      earlier in ACL(INT) than in ACL(REC) subjects. Lateral gastrocnemius (LG) and MG
      muscle peak times were 106 ms and 87 ms earlier in females than in males,
      respectively. The RF, VM, BF, and MG peaked later in ACL(REC) than in ACL(INT)
      subjects. There was evidence suggesting that the loading phase
      quadriceps:hamstring (quad:ham) muscle activity ratio was greater in ACL(REC)
      than in ACL(INT) subjects. Finally, the injury risk phase quad:ham muscle
      activity ratio was 4.8 times greater in females than in males. In conclusion,
      differences exist in muscle activity related to ACL status and sex that could
      potentially help explain graft failure risk and the sex bias.

PMID- 23966335
TI  - Thymine modified amphiphilic biodegradable copolymers for photo-cross-linked
      micelles as stable drug carriers.
AB  - A photo-cross-linked micelle is synthesized via photodimerization of thymine
      moieties fabricated from amphiphilic block copolymers (mPEG-b-P(LA-co-MPT). The
      crosslinking behavior is monitored by UV-Vis spectra and (1) H NMR. Dynamic light
      scattering (DLS) and transmission electron microscopy (TEM) showed that cross
      linked micelles had smaller sizes than their uncross-linked precursors. In vitro
      studies reveal that cross-linking of the micelle cores results in a slow drug
      release and faster cellular uptake in comparison with uncross-linked ones in MCF
      7 and Hela cells. Moreover, the paclitaxel (PTX)-loaded core-cross-linked
      micelles exhibit similar anticancer efficacy as free PTX. This work provides a
      convenient tool for designing a more stable structure in the blood circulation to
      realize a controlled drug delivery. 

PMID- 23966336
TI  - The upside of downsizing: asymmetric trifunctional organocatalysts as small
      enzyme mimics for cooperative enhancement of both rate and enantioselectivity
      with regulation.
AB  - Small molecule organic catalysts (organocatalysts) are widely used in asymmetric
      catalysis and synthesis. Compared to their enzymatic and transition-metal
      counterparts, organocatalysts have advantages in catalytic scope and efficiency
      but are more limited in proficiency. Chiral trifunctional organocatalysts, in
      which multiple catalytic motifs act cooperatively on a chiral scaffold, are an
      emerging class of organocatalysts with improved proficiency. Cooperativity design
      that enables both enantioselectivity and rate enhancement is essential to
      developing future generations of organocatalysts in biomimetic asymmetric
      catalysis.

PMID- 23966337
TI  - Transmenopausal changes in trabecular bone quality.
AB  - Bone strength depends on its amount and quality. Bone quality includes its
      structural and material properties. Bone material properties are dependent on
      bone turnover rates. Remodeling rates are significantly increased immediately
      after menopause. In the present study, we used Raman microspectroscopic analysis
      of double iliac crest biopsies with a spatial resolution of 1 um obtained before
      and immediately after menopause (1 year after cessation of menses) in healthy
      females to investigate changes in material properties attributable to menopause.
      In particular, the mineral/matrix ratio, the relative proteoglycan and lipid
      content, the mineral maturity/crystallinity, and the relative pyridinoline
      collagen cross-link content were determined in trabecular bone as a function of
      surface metabolic activity and tissue age. The results indicate that significant
      changes (specifically in mineral/matrix ratio) were evident at active bone
      forming surfaces, whereas the relative proteoglycan content was altered at
      resorbing surfaces. These changes were not accompanied by altered mineral content
      or quality as monitored by Raman microspectroscopic analysis.

PMID- 23966338
TI  - Rectal douching and implications for rectal microbicides among populations
      vulnerable to HIV in South America: a qualitative study.
AB  - OBJECTIVE: While gel-formulated rectal microbicides (RM) are the first to enter
      clinical trials, rectal douching in preparation for anal intercourse is a common
      practice; thus RMs formulated as douches may be a convenient alternative to gels.
      Nonetheless, little is known about potential users' thoughts regarding douche
      formulated RMs or rectal douching practices, data that is needed to inform the
      advancement of douche-based RMs. This qualitative study examined thoughts
      regarding douches, their use as an RM and current douching practices among men
      who have sex with men and transgender women. METHODS: 12 focus groups and 36 in
      depth interviews were conducted (N=140) to examine the overall acceptability of
      RM, of which one component focused on rectal douching. Focus groups and
      interviews were recorded, transcribed verbatim and coded; text relating to rectal
      douching was extracted and analysed. Sociodemographic information was collected
      using a self-administered questionnaire. RESULTS: Support for a douche-formulated
      RM centred on the possibility of combined precoital hygiene and HIV protection,
      and it was believed that a deeply penetrating liquid douche would confer greater
      HIV protection than a gel. Drawbacks included rectal dryness, impracticality and
      portability issues, and potential side effects. Non-commercial douching apparatus
      use was common and liquids used included detergents, vinegar, bleach, lemon juice
      and alcohol. CONCLUSIONS: A douche-formulated RM, while desirable and perceived
      as more effective than a gel-formulated RM, also generated questions regarding
      practicality and side effects. Of immediate concern were the non-commercial
      liquids already being used that likely damage rectal epithelia, potentially
      increasing HIV infection risk. Precoital rectal douching is common and an RM
      formulated as such is desirable, but education on rectal douching practices is
      needed now.

PMID- 23966339
TI  - STI testing without HIV disclosure by MSM with diagnosed HIV infection in
      England: cross-sectional results from an online panel survey.
AB  - OBJECTIVES: To explore the reasons why men who have sex with men (MSM) with
      diagnosed HIV test for sexually transmitted infections (STIs) away from their
      usual care provider without disclosing their HIV infection. METHODS: Cross
      sectional internet panel survey of MSM. RESULTS: 9.4% of men with diagnosed HIV
      reported ever testing for STIs away from their usual HIV care provider without
      disclosing their HIV infection, and 4.4% had done so in the last year. Reported
      benefits were the convenience of using an alternative service and the avoidance
      of disclosing risky sexual behaviour to known HIV care providers. The impact on
      continuity of care was seen as a disadvantage of seeking STI screening away from
      usual care providers. A minority of men who attended an alternative service
      reported having an HIV test. CONCLUSIONS: Prevalence estimates of undiagnosed HIV
      among MSM may be inflated because some men with diagnosed HIV seek STI testing
      away from their usual care provider without disclosing their HIV infection or
      accepting an HIV test. Our data suggest that the reasons for doing so are
      convenience and discomfort about disclosing risky sexual behaviour to HIV care
      providers.

PMID- 23966340
TI  - Enhanced hippocampal neuronal excitability and LTP persistence associated with
      reduced behavioral flexibility in the maternal immune activation model of
      schizophrenia.
AB  - Individuals with schizophrenia display a number of structural and
      cytoarchitectural alterations in the hippocampus, suggesting that other functions
      such as synaptic plasticity may also be modified. Altered hippocampal plasticity
      is likely to affect memory processing, and therefore any such pathology may
      contribute to the cognitive symptoms of schizophrenia, which includes prominent
      memory impairment. The current study tested whether prenatal exposure to
      infection, an environmental risk factor that has previously been associated with
      schizophrenia produced changes in hippocampal synaptic transmission or
      plasticity, using the maternal immune activation (MIA) animal model. We also
      assessed performance in hippocampus-dependent memory tasks to determine whether
      altered plasticity is associated with memory dysfunction. MIA did not alter basal
      synaptic transmission in either the dentate gyrus or CA1 of freely moving adult
      rats. It did, however, result in increased paired-pulse facilitation of the
      dentate gyrus population spike and an enhanced persistence of dentate long-term
      potentiation. MIA animals displayed slower learning of a reversed platform
      location in the water maze, and a similarly slowed learning during reversal in a
      spatial plus maze task. Together these findings are indicative of reduced
      behavioral flexibility in response to changes in task requirements. The results
      are consistent with the hypothesis that hippocampal plasticity is altered in
      schizophrenia, and that this change in plasticity mechanisms may underlie some
      aspects of cognitive dysfunction in this disorder.

PMID- 23966341
TI  - Chirality: a relational geometric-physical property.
AB  - The definition of the term chirality by Lord Kelvin in 1893 and 1904 is analyzed
      by taking crystallography at that time into account. This shows clearly that
      chirality is a relational geometric-physical property, i.e., two relations
      between isometric objects are possible: homochiral or heterochiral. In scientific
      articles the relational term chirality is often mistaken for the two valued
      measure for the individual (absolute) sense of chirality, an arbitrary
      attributive term.

PMID- 23966342
TI  - Chitosan-based nanocoatings for hypothermic storage of living cells.
AB  - The formation of ultrathin chitosan-based nanocoating on HL-60 model cells and
      their protective function in hypothermic storage are presented. HL-60 cells are
      encapsulated in ultrathin shells by adsorbing cationic and anionic chitosan
      derivatives in a stepwise, layer-by-layer, procedure carried out in an aqueous
      medium under mild conditions. The chitosan-based films are also deposited on
      model lipid bilayer and the interactions are studied using ellipsometry and
      atomic force microscopy. The cells covered with the chitosan-based films and
      stored at 4  degrees C for 24 h express viability comparable to that of the
      control sample incubated at 37  degrees C, while the unprotected cells stored
      under the same conditions do not show viability. It is shown that the chitosan
      based shell protects HL-60 cells against damaging effect of hypothermic storage.
      Such nanocoatings provide protection, mechanical stability, and support the cell
      membrane, while ensuring penetration of small molecules such as nutrients/gases
      what is essential for cell viability. 

PMID- 23966343
TI  - Redefining the activity of a bone-specific transcription factor: novel insights
      for understanding bone formation.

PMID- 23966344
TI  - Natural variations in snow cover do not affect the annual soil CO2 efflux from a
      mid-elevation temperate forest.
AB  - Climate change might alter annual snowfall patterns and modify the duration and
      magnitude of snow cover in temperate regions with resultant impacts on soil
      microclimate and soil CO2 efflux (Fsoil ). We used a 5-year time series of Fsoil
      measurements from a mid-elevation forest to assess the effects of naturally
      changing snow cover. Snow cover varied considerably in duration (105-154 days)
      and depth (mean snow depth 19-59 cm). Periodically shallow snow cover (<10 cm)
      caused soil freezing or increased variation in soil temperature. This was mostly
      not reflected in Fsoil which tended to decrease gradually throughout winter.
      Progressively decreasing C substrate availability (identified by substrate
      induced respiration) likely over-rid the effects of slowly changing soil
      temperatures and determined the overall course of Fsoil . Cumulative CO2 efflux
      from beneath snow cover varied between 0.46 and 0.95 t C ha(-1)  yr(-1) and
      amounted to between 6 and 12% of the annual efflux. When compared over a fixed
      interval (the longest period of snow cover during the 5 years), the cumulative
      CO2 efflux ranged between 0.77 and 1.18 t C ha(-1) or between 11 and 15% of the
      annual soil CO2 efflux. The relative contribution (15%) was highest during the
      year with the shortest winter. Variations in snow cover were not reflected in the
      annual CO2 efflux (7.44-8.41 t C ha(-1) ) which did not differ significantly
      between years and did not correlate with any snow parameter. Regional climate at
      our site was characterized by relatively high amounts of precipitation.
      Therefore, snow did not play a role in terms of water supply during the warm
      season and primarily affected cold season processes. The role of changing snow
      cover therefore seems rather marginal when compared to potential climate change
      effects on Fsoil during the warm season. 

PMID- 23966345
TI  - A model for the differentiation between grid and conjunctive units in medial
      entorhinal cortex.
AB  - The multiple layers of medial entorhinal cortex (mEC) contain cells that differ
      in selectivity, connectivity, and cellular properties. Grid cells in layer II and
      in the deeper layers express triangular grid patterns in the environment. The
      firing rate of the conjunctive cells found in layer III and below, on the other
      hand, show grid-by-head direction tuning. In this study, we model the
      differentiation between grid and conjunctive cells in a network with self
      organized connections. Arranged into distinct "layers", the model grid units and
      conjunctive units develop, with a similar time course, grid fields resulting from
      firing rate adaptation and competitive learning. Grid alignment in both layers is
      delayed with respect to the formation of triangular grids. A common grid
      orientation among conjunctive units is produced, in the model, by head-direction
      modulated collateral interactions, while the grids of grid units inherit the same
      orientation through connections from conjunctive units. Grid units as well as
      conjunctive units share a similar spacing but show a random distribution of
      spatial phases. Grid units however carry more spatial information than
      conjunctive units, thus providing better inputs for the hippocampus to form
      spatial memories.

PMID- 23966346
TI  - Nonaqueous capillary electrophoretic enantioseparation of water insoluble
      Troger's base derivatives using beta-cyclodextrin as chiral selector.
AB  - Racemic mixtures of six Troger's base derivatives were separated by chiral
      nonaqueous capillary electrophoresis. The separation protocol was optimized first
      for suitable solvents. Then the applicability of various salts dissolved in
      organic solvents and their mixtures was evaluated. As chiral selectors beta
      cyclodextrin and heptakis(2,6-di-O-methyl)-beta-cyclodextrin at various
      concentrations were used. The best enantioselectivity for the studied analytes
      was obtained utilizing formamide as organic nonaqueous solvent containing a
      mixture of sodium citrate and tris(hydroxymethyl)aminomethane acetate as
      electrolytes, and beta-cyclodextrin as chiral additive. The experimental results
      demonstrated the feasibility of nonaqueous capillary electrophoresis for
      enantioseparation of Troger's base derivatives. This technique represents a
      suitable alternative to more commonly used capillary electrophoresis in aqueous
      environment.

PMID- 23966348
TI  - Acute onset anarthria without hepatic manifestation: a rare presentation of
      Wilson disease.
AB  - Wilson disease (WD) is one of the few inherited but treatable disorder mainly
      affecting the liver and brain resulting in severe disability or death if left
      untreated. Hence, it is important to keep a high index of suspicion for
      diagnosing this clinical entity in appropriate clinical settings. The clinical
      presentation can be quite variable and they may present solely with neurological
      features sans hepatic symptoms. Such neurological manifestations usually follow
      subacute to chronic course. Acute onset anarthria as the heralding and
      predominant presenting feature has been rarely reported in the literature. We
      reported a case of a 12-year-old girl who presented with acute onset anarthria
      and dystonia of 1-month duration. On further evaluation, a diagnosis of WD was
      made. The patient showed partial improvement after she was started on copper
      chelating agents and anticholinergics. 

PMID- 23966347
TI  - Reversal of lung cancer multidrug resistance by pH-responsive micelleplexes
      mediating co-delivery of siRNA and paclitaxel.
AB  - The recent advances in RNA interference (RNAi) technology provided novel and
      promising solutions for human cancer treatment. In this study, the application of
      dual pH-responsive cationic micellar nanoparticles for small interfering RNA
      (siRNA) and paclitaxel (PTX) co-delivery to overcome cancer multidrug resistance
      (MDR) is reported. The in vitro siRNA transfection shows that siRNA-luciferase
      (Luc) loaded micelleplexes efficiently silences Luc expression in various
      carcinoma cell lines. The Luc knockdown ability of the micelleplexes can be
      enhanced by choloquine (CQ) co-incubation. However, is abolished by bafilomycin
      A1 (Baf-A1) treatment. The micelleplexes are further exploited for co-delivery of
      siRNA-Bcl-2 and PTX to Bcl-2 overexpressing A549 lung cancer cells (A549-Bcl-2).
      The experimental results show that the micelleplexes could sensitize A549-Bcl-2
      cells to PTX via down-regulation of anti-apoptosis gene of Bcl-2, suggesting that
      PDMA-b-PDPA micelleplexes are promising nanovectors for siRNA and anti-cancer
      drug co-delivery to overcome cancer MDR. 

PMID- 23966349
TI  - Simulating greenhouse gas mitigation potentials for Chinese Croplands using the
      DAYCENT ecosystem model.
AB  - Understanding the potential for greenhouse gas (GHG) mitigation in agricultural
      lands is a critical challenge for climate change policy. This study uses the
      DAYCENT ecosystem model to predict GHG mitigation potentials associated with soil
      management in Chinese cropland systems. Application of ecosystem models, such as
      DAYCENT, requires the evaluation of model performance with data sets from
      experiments relevant to the climate and management of the study region. DAYCENT
      was evaluated with data from 350 cropland experiments in China, including
      measurements of nitrous oxide emissions (N2 O), methane emissions (CH4 ), and
      soil organic carbon (SOC) stock changes. In general, the model was reasonably
      accurate with R(2) values for model predictions vs. measurements ranging from
      0.71 to 0.85. Modeling efficiency varied from 0.65 for SOC stock changes to 0.83
      for crop yields. Mitigation potentials were estimated on a yield basis (Mg CO2 
      equivalent Mg(-1) Yield). The results demonstrate that the largest decrease in
      GHG emissions in rainfed systems are associated with combined effect of reducing
      mineral N fertilization, organic matter amendments and reduced-till coupled with
      straw return, estimated at 0.31 to 0.83 Mg CO2 -equivalent Mg(-1) Yield. A
      mitigation potential of 0.08 to 0.36 Mg CO2 -equivalent Mg(-1) Yield is possible
      by reducing N chemical fertilizer rates, along with intermittent flooding in
      paddy rice cropping systems. 

PMID- 23966350
TI  - Gambling, Delay, and Probability Discounting in Adults With and Without ADHD.
AB  - OBJECTIVE: We investigated the relationship between impulsivity, as measured by
      delay and probability discounting, and gambling-related cognitions and behavior
      in adults with and without ADHD. METHOD: Adults who met Diagnostic and
      Statistical Manual of Mental Disorders (4th ed.; DSM-IV) diagnostic criteria for
      ADHD (n = 31) and controls (n = 29) were recruited from the community. All
      completed an interview that included an assessment of psychiatric disorders,
      gambling questionnaires, and simulated gambling, delay, and probability
      discounting tasks. RESULTS: The ADHD group was more likely to meet the criteria
      for problem gambling and was more impulsive than controls based on a composite
      discounting measure. ADHD symptoms were correlated with gambling-related
      cognitions and behavior. Probability, but not delay discounting, explained
      significant variance in gambling-related measures after controlling for ADHD
      symptoms. DISCUSSION: Results confirm an association between adult ADHD and
      gambling, and suggest that the facets of impulsivity related to risk proneness
      may be an independent risk factor for problem gambling in this population.

PMID- 23966351
TI  - Lobeline Effects on Cognitive Performance in Adult ADHD.
AB  - OBJECTIVE: In preclinical studies, lobeline inhibited hyperactivity induced by
      nicotine and amphetamine, and improved performance and learning in studies
      utilizing radial-arm maze and spatial-discrimination water maze. This laboratory
      proof-of-concept study investigated lobeline as a treatment for ADHD symptoms in
      adults (31.11 +/- 7.08 years). METHOD: Using cognitive tasks and self-report
      measures, the effects of lobeline (0, 7.5, 15, or 30 mg, s.l.) and
      methylphenidate (0, 15, or 30 mg, p.o.) were assessed in nine volunteers with
      ADHD. RESULTS: Evidence suggested that lobeline could modestly improve working
      memory in adults with ADHD, but no significant improvement in attention was
      observed. Lobeline administration was associated with mild adverse side effects
      (nausea). CONCLUSION: Further investigation of lobeline on working memory may be
      warranted.

PMID- 23966352
TI  - Effect of External Irrelevant Distracters on a Visual Search Test in School-Age
      Children: Computerized Assessment.
AB  - OBJECTIVE: This study aimed to test the effect of an irrelevant external
      distracter included in a computer-administered visual search test. Two hypotheses
      were tested: (a) If the distracter affects performance, attention efficiency will
      be lowered; (b) if children do not habituate to the distracter, performance will
      be lower for every item of the test. METHOD: Distraction was induced changing the
      screen color unexpectedly several times in each trial-450 children (225 girls and
      225 boys) from second to sixth course were tested. This group was compared with a
      group of 423 children from the same age range who were tested with the same test
      without distraction. RESULTS: Induced distraction reduced attention efficiency
      for all ages and for every trial in the treatment group (test with distraction).
      Speed was lower, but number of errors did not increase. CONCLUSION: School-age
      children cope with an irrelevant external distracter by reducing speed, not
      accuracy.

PMID- 23966354
TI  - How do experts reporting for the legal process validate symptoms? The results of
      a survey.
AB  - This article examines the views of experts from a range of disciplines and how
      they view symptoms given to them by claimants in matters of personal injury or
      medical negligence assessments. The survey was carried out in 2009 and looks at
      current practice and attitudes from a number of different disciplines. The survey
      included questions looking at what percentage of cases were thought to be
      genuine, symptoms most likely to be elaborated, methods for assessing symptom
      validity, and documentary evidence required for a report. This article highlights
      the importance of looking at symptom validation in the legal process. 

PMID- 23966353
TI  - Study on unnatural childhood deaths presented to North Colombo Teaching Hospital,
      Sri Lanka.
AB  - INTRODUCTION: Unnatural childhood deaths are not only associated with intense
      trauma and separation distress, but also relate to a sense of neglect to protect
      children from harm. Accurate information on causes and circumstances of such
      deaths through a process of medico-legal investigations is essential in creating
      an awareness among the policy makers and educators/caregivers, to prevent these
      tragic deaths. OBJECTIVE: The aim of the study was to determine the causes and
      the circumstances of unnatural deaths of children among the medico-legal autopsy
      population presented to North Colombo Teaching Hospital, Sri Lanka. STUDY DESIGN:
      A retrospective descriptive study was carried out based on Reports of Postmortem
      Examination performed in a Tertiary Care Hospital, on children who died of
      unnatural causes during the period from 2009 to 2011. RESULTS: Out of 48
      unnatural childhood deaths, 24 (50%) children were older than 10 years of age.
      The most frequent circumstance of death was accidental 39 (81%), while the most
      frequent cause of death was drowning 16 (33%). Fifteen died due to accidental
      drowning while one was a homicidal drowning. Suicidal deaths were found only
      among the children older than 16 years of age. Fifty-four percent of the
      accidental deaths had taken place at or around the home. CONCLUSION: Accidents
      accounted for the majority (or greatest number) of tragic childhood deaths. The
      presence of drowning as the most common cause of death indicates that an immense
      responsibility lies with the parents and caregivers to prevent such deaths.

PMID- 23966355
TI  - The chronology of third molar root mineralization in south Indian population.
AB  - The aim of present study was to determine the chronology of third molar root
      mineralization and to establish south Indian reference data. Therefore, a cross
      sectional study was undertaken by evaluating 192 intraoral periapical radiographs
      in order to assess the root mineralization status of the mandibular third molar
      of south Indian individuals (101 males and 91 females) between the age of 13 and
      25. The evaluation was carried out using the seven-stage developmental scheme of
      Kullman et al. (1992). The range, mean age, standard deviation, Student t test
      and percentile distributions are presented for each stage of mineralization.
      Statistically significant differences between males and females were not found.
      All individuals from this study with mature third molar roots were at least 18
      years of age. For medicolegal purposes, the likelihood of whether a south Indian
      individual is older than 18 years or not was determined. 

PMID- 23966356
TI  - Crystallographic, spectroscopic, and theoretical investigation of the efficiently
      separated 21R and 21S-diastereoisomers of argatroban.
AB  - Argatroban (I), a potent noncovalent reversible thrombin inhibitor, is used as an
      anticoagulant for the parenteral treatment of heparin-induced thrombocytopenia
      (HIT) patients. By virtue of its pharmacological properties and the well-balanced
      risks and benefits, argatroban is now emerging as a clinically relevant
      antithrombotic agent. The availability of this drug as a mixture of 21R and 21S
      diastereoisomers, in a ratio of roughly 64:36, prompted us to design an efficient
      separation setup of the two epimers. We pursued our efforts on their detailed
      structural analysis with the aim of understanding their different activity and
      aqueous solubility. These investigations were accompanied by a modeling study of
      the two diastereoisomers, with particular attention on the easy interconverting
      half-chair of the tetrahydroquinoline system and its preferred conformation,
      which is determined by the configuration at C21. These results, together with the
      analysis of their physicochemical profiles, provide new useful information for
      the development of the individual diastereoisomers.

PMID- 23966357
TI  - Enhanced cellular transfection by ternary non-viral gene vectors coupled with
      adeno-associated virus-derived peptides.
AB  - The establishment of efficient and safe gene delivery systems is crucial for
      biomedical applications. To address this objective, novel, ternary hybrid gene
      vectors are designed with viral capsid peptides in non-viral gene carriers. The
      viral peptide, TQVGQKT, is coupled with a membrane active peptide, LK15. Which
      acts as a linker to tag peptide with plasmid DNA. Additionally, polyethylenimine
      (PEI) is employed to condense the complexes further, thereby forming ternary
      DNA/TQVGQKT-LK15/PEI complexes. The ternary complexes result in rapid
      internalization leading to significantly enhanced cellular transfection. The new
      moiety, TQVGQKT, as well as enhanced cellular transfection, will certainly
      provide crucial insights for the design of novel non-viral gene carriers with
      efficient and safe properties. 

PMID- 23966358
TI  - Effects of ocean warming and acidification on the energy budget of an excavating
      sponge.
AB  - Recent research efforts have demonstrated increased bioerosion rates under
      experimentally elevated partial pressures of seawater carbon dioxide (pCO2 ) with
      or without increased temperatures, which may lead to net erosion on coral reefs
      in the future. However, this conclusion clearly depends on the ability of the
      investigated bioeroding organisms to survive and grow in the warmer and more
      acidic future environments, which remains unexplored. The excavating sponge
      Cliona orientalis Thiele, is a widely distributed bioeroding organism and
      symbiotic with dinoflagellates of the genus Symbiodinium. Using C. orientalis, an
      energy budget model was developed to calculate amounts of carbon directed into
      metabolic maintenance and growth. This model was tested under a range of CO2
      emission scenarios (temperature + pCO2 ) appropriate to an Austral early summer.
      Under a pre-industrial scenario, present day (control) scenario, or B1 future
      scenario (associated with reducing the rate of CO2 emissions over the next few
      decades), C. orientalis maintained a positive energy budget, where metabolic
      demand was likely satisfied by autotrophic carbon provided by Symbiodinium and
      heterotrophic carbon via filter-feeding, suggesting sustainability. Under B1, C.
      orientalis likely benefited by a greater supply of photosynthetic products from
      its symbionts, which increased by up to 56% per unit area, and displayed an
      improved condition with up to 52% increased surplus carbon available for growth.
      Under an A1FI future scenario (associated with 'business-as-usual' CO2 emissions)
      bleached C. orientalis experienced the highest metabolic demand, but carbon
      acquired was insufficient to maintain the sponge, as indicated by a negative
      energy budget. These metabolic considerations suggest that previous observations
      of increased bioerosion under A1FI by C. orientalis may not last through the
      height of future A1FI summers, and survival of individual sponges may be
      dependent on the energy reserves (biomass) they have accumulated through the rest
      of the year. 

PMID- 23966359
TI  - Murine marginal zone B cells play a role in Vibrio cholerae LPS antibody
      responses.
AB  - The emergence of Vibrio cholerae (Vc) lipopolysaccharide (LPS) as a lead
      protective antigen for a cholera subunit vaccine has increased the interest in
      what type of B cell is best suited to generate anti-Vc LPS antibodies. A related
      question is what form of LPS is the most immunogenic. C57Bl/6 (B6) neonatal mice
      (10 days old) whose marginal zone (MZ) B cell compartment is still maturing and
      two lines of knockout mice that either lack the signaling mechanism required for
      the maturation of MZ B cells or that lack a receptor required for MZ B cell
      retention in the MZ were used to determine the role of MZ B cells in anti-Vc LPS
      antibody responses. Data support the conclusion that MZ B cells play a
      significant role in the anti-Vc LPS antibody response. Serum and vibriocidal
      antibody titers also depend on whether the Vc LPS is purified or bacterial cell
      associated. 

PMID- 23966360
TI  - Effect of imatinib on male reproductive hormones in BCR-ABL positive CML
      patients: A preliminary report.
AB  - Multiple animal studies, few clinical case reports and one study have observed
      decreased testosterone production and gynaecomastia as adverse effect of imatinib
      therapy. We have prospectively studied testosterone, LH and FSH levels at
      baseline and at 6 months of imatinib treatment in 34 newly diagnosed male BCR-ABL
      positive CML patients. While none of the patients had gynaecomastia at 6 months,
      the proportion of patients with low testosterone level increased significantly
      from 11.8% at baseline to 58.8% (p < 0.001) and those with high LH and FSH
      increased significantly from 26.4% and 23.5% to 82.4% and 76.4%, respectively (p
      < 0.001 and p < 0.001). Serum testosterone levels decreased significantly (p =
      0.002) and serum LH and FSH levels increased significantly at 6 months of
      imatinib therapy (p = 0.001 and p = 0.003) in comparison to baseline levels. The
      findings document the effect of imatinib on testosterone levels in adult CML
      patients much before than reported earlier. 

PMID- 23966363
TI  - Design, synthesis and herbicidal activities of novel 4-(1H-pyrazol-1-yl)-6
      (alkynyloxy)-pyrimidine derivatives as potential pigment biosynthesis inhibitors.
AB  - BACKGROUND: With the objective of finding novel valuable herbicidal candidates, a
      series of novel 4-(1H-pyrazol-1-yl)-6-(alkynyloxy)-pyrimidine derivatives were
      synthesised and their herbicide activities were evaluated in vivo. RESULTS: The
      results showed that many target compounds expressed bleaching activities. Among
      these, compound 5 h showed the best bleaching activity to gramineous weeds, being
      able to produce the highest inhibition of chlorophyll level in seedlings of
      Pennisetum alopecuroides L. (IC50 = 3.48 mg L(-1) ). Moreover, compound 5 h
      expressed good selective toxicity between gramineous P. alopecuroides L. and
      broadleaf plant Brassica campestris L. CONCLUSIONS: The present work demonstrates
      that pyrimidine derivatives containing pyrazole can be used as potential lead
      compounds for developing novel pigment biosynthesis inhibitors.

PMID- 23966364
TI  - Multi-pelvis characterisation of articular cartilage geometry.
AB  - The shape of the acetabular cartilage follows the contact stress distribution
      across the joint. Accurate characterisation of this geometry may be useful for
      the development of acetabular cup devices that are more biomechanically
      compliant. In this study, the geometry of the acetabular cartilage was
      characterised by taking plaster moulds of the acetabulum from 24 dry bone human
      pelvises and digitising the mould shapes using a three-dimensional laser scanner.
      The articular bone surface geometry was analysed, and the shape of the acetabulum
      was approximated by fitting a best-fit sphere. To test the hypothesis that the
      acetabulum is non-spherical, a best-fit ellipsoid was also fitted to the
      geometry. In each case, points around the acetabular notch edge that disclosed
      the articular surface geometry were identified, and vectors were drawn between
      these and the best-fit sphere or ellipsoid centre. The significantly larger z
      radii (into the pole) of the ellipsoids indicated that the acetabulum was non
      spherical and could imply that the kinematics of the hip joint is more complex
      than purely rotational motion, and the traditional ball-and-socket replacement
      may need to be updated to reflect this motion. The acetabular notch edges were
      observed to be curved, with males exhibiting deeper, wider and shorter notches
      than females, although the difference was not statistically significant (mean: p
      = 0.30) and supports the use of non-gender-specific models in anatomical studies.

PMID- 23966365
TI  - Computed tomography and magnetic resonance imaging findings of inflammatory
      myofibroblastic tumors of the head and neck.
AB  - BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare tumor of
      mesenchymal origin that commonly occurs in the lung. Because of its non-specific
      clinical and imaging features, IMT is often misdiagnosed as a malignant tumor.
      There have been few imaging reports on IMT of the head and neck. PURPOSE: To
      analyze the computed tomography (CT) and magnetic resonance imaging (MRI)
      findings of inflammatory myofibroblastic tumors (IMTs) of the head and neck.
      MATERIAL AND METHODS: Six patients with IMTs of the head and neck confirmed by
      histopathologic examination were analyzed retrospectively. RESULTS: The mean
      patient age was 40 years. The tumor locations in the six patients were as
      follows: left bridge of the nose (one), right infratemporal fossa (two), and left
      parotid gland (three). Three patients who underwent CT all had soft tissue masses
      or nodules and no calcification. Bridge of the nose tumor showed a homogeneous
      isodense nodule and mild homogeneous enhancement. Infratemporal fossa tumor
      showed a homogeneous low density mass and intermediate homogeneous enhancement.
      Left parotid gland tumor showed a heterogeneous, mostly low density mass, and
      intermediate heterogeneous enhancement. T1-weighted images of the parotid gland
      tumors were hypointense; the infratemporal fossa tumor was isointense. T2
      weighted images were mildly hypointense and of mixed hypo- and isointensity in
      the two parotid gland tumors; the infratemporal fossa tumor was homogeneously
      mildly hypointense. Heterogeneous intermediate enhancement was demonstrated in
      one parotid gland and the infratemporal fossa patients and mild homogeneous
      enhancement in another parotid gland patient. CONCLUSION: The imaging features of
      IMTs of the head and neck are non-specific. An ill-defined, aggressive mass and
      variable enhancement on CT and MRI may suggest the diagnosis of IMT. IMT should
      be included in the differential diagnosis of regional tumors.

PMID- 23966366
TI  - Incidental findings in computed tomographic angiography for planning percutaneous
      aortic valve replacement: advanced age, increased cancer prevalence?
AB  - BACKGROUND: Increased age is linked with a higher cancer risk according to model
      calculations. Patients with severe atherosclerotic aortic stenosis are of old
      age, therefore, a high incidence of malignancies should be found. PURPOSE: To
      evaluate the prevalence of clinically significant and potentially malignant
      incidental findings at computed tomographic angiography (CTA) performed in
      patients with severe aortic stenosis being assessed as to their suitability for
      transcatheter aortic valve replacement (TAVR). MATERIAL AND METHODS: Between
      August 2008 and April 2010, CTA of the thoraco-abdominal aorta and the pelvic
      arterial vessels was performed in 131 patients. There were 62 women (47%) and 69
      men (53%); the mean age was 81.6 years (range, 64-91 years). Incidental findings
      were recorded and categorized as potentially malignant, clinically significant,
      and clinically insignificant. Clinically significant findings were defined as
      those requiring immediate therapy, intervention or imaging, or follow-up
      examination. RESULTS: Of the 131 study patients, 31 (23.7%) presented significant
      extravascular incidental findings, 19 (14.5%) in the thorax, and 12 (9.2%) in the
      abdomen. Five lesions (3.8%) were considered potentially malignant, three of them
      (2.3%) were new and highly suspicious for malignancies (two renal cell carcinomas
      and one hepatocellular carcinoma). In two patients (1.5%) mediastinal
      lymphadenopathy was found (recurrent malignant lymphoma und new metastases from
      known bladder cancer). CONCLUSION: The prevalence of highly suspicious malignant
      incidental findings in patients undergoing TAVR is 3.8% with an average age of
      81.6 years which is not high compared to prevalence in the literature dealing
      with patients aged <70 years.

PMID- 23966367
TI  - White matter atrophy in brain of neuromyelitis optica: a voxel-based morphometry
      study.
AB  - BACKGROUND: Recent studies have shown that tissue damage in neuromyelitis optica
      (NMO) is not limited to the spinal cord and optic nerve but can also appear in
      the brain. Previous magnetic resonance imaging (MRI) studies have reported
      controversial findings regarding the presence of white matter atrophy in NMO
      patients. PURPOSE: To investigate regional white matter changes in NMO using
      voxel-based morphometry (VBM). MATERIAL AND METHODS: Conventional MRI and T1
      weighted three-dimensional MRI were performed on 20 patients with NMO and 20 age-
      and sex-matched normal controls (NCs). The data were analyzed by statistical
      parametric mapping 5 (SPM5) to generate white matter concentration maps, and
      regional white matter concentrations were compared between the two groups.
      Relationships between the white matter concentration in regions with significant
      group differences and the Expanded Disability Status Scale (EDSS) and disease
      duration were further explored. RESULTS: Compared to NCs, NMO patients had
      decreased white matter volumes in the right precentral gyrus, right postcentral
      gyrus, left middle and medial frontal gyrus, right superior frontal gyrus,
      bilateral inferior and superior parietal lobule, right angular gyrus, right
      middle occipital gyrus, and left precuneus. No significant correlation was found
      between white matter regions with volume reduction and the EDSS and disease
      duration in NMO. CONCLUSION: We found white matter atrophy in several brain
      regions in the frontal, parietal, and occipital lobes in NMO, suggesting that
      subtle white matter damage relevant to the motor, vision, and cognition systems
      exists in NMO patients. The pattern of white matter atrophy in NMO is different
      from that in multiple sclerosis (MS).

PMID- 23966368
TI  - Non-responders to treatment with antagonists of vascular endothelial growth
      factor in age-related macular degeneration.
AB  - PURPOSE: Most of the publications on modern therapy of neovascular age-related
      macular degeneration focus on the effect of the treatment. The purpose of this
      study is to determine the frequency of non-responders to anti-vascular
      endothelial growth factor (anti-VEGF) treatment and find possible reasons for
      their failure to respond. METHODS: The records of patients treated until the end
      of 2008 the first time with either bevacizumab or ranibizumab were reviewed.
      Based on the availability of measurable results and according to prior
      publications showing the effect of the therapy, loss of three lines of distance
      acuity, increase of retinal thickness or lesion size were identified as
      indicators of non-responders. Two of these three signs had to be present.
      RESULTS: 334 eyes of 283 patients were included; 74.55% received bevacizumab and
      25.45% received ranibizumab. Overall 14.37% of the eyes were identified as non
      responders (14.06% in the bevacizumab group and 15.29% in the ranibizumab group).
      Baseline distance acuity and vitreo-retinal adhesions were significantly
      correlated with non-responders. Correlations with age, gender, lesion type, other
      morphologic features, and the kind of anti-VEGF agent failed to be significant.
      10.4% of the non-responders showed a delayed but good response to anti-VEGF
      treatment. CONCLUSIONS: About 15% did not sufficiently respond to anti-VEGF
      treatment. Vitreo-retinal adherences were the only ophthalmologic factor which
      could be identified to be significantly correlated with insufficient response.

PMID- 23966369
TI  - Cataract surgery outcome in eyes with keratoconus.
AB  - BACKGROUND: To review the refractive outcome of cataract surgery in eyes with
      keratoconus. METHODS: We retrospectively reviewed the medical records of 64
      consecutive patients (92 eyes) who underwent cataract surgery with implantation
      of a spherical intraocular lens (IOL). We recorded the method of refractive
      correction and the effect of the keratometry (K) on the biometry prediction error
      (BPE). RESULTS: 35 eyes had mild keratoconus (mean K<48 dioptres (D)), 40 had
      moderate keratoconus (mean K 48 D to 55 D) and 17 had severe keratoconus (mean
      K>55 D). Actual K values were used in all eyes with mild or moderate keratoconus
      with a target refraction of approximately -1.0 D in mild keratoconus and -1.5 D
      in moderate keratoconus that resulted in a mean BPE of 0.0 D and +0.3 D,
      respectively. The actual K values were used in eight of the 17 eyes with severe
      keratoconus with a mean target refraction of -5.4 D, which resulted in a mean BPE
      of +6.8 D. In the remaining nine eyes, a standard K value of 43.25 D was used
      with a mean target refraction of -1.8 D, which resulted in a mean BPE of +0.6 D.
      CONCLUSIONS: Using the actual K values with a target of low myopia is a suitable
      option for spherical IOL selection for eyes with a mean K of <=55 D. When there
      is severe keratoconus, the use of actual K values can result in a large hyperopic
      error and the use of standard K value in these eyes should be considered.

PMID- 23966370
TI  - Association of CFH and SERPING1 polymorphisms with anterior uveitis.
AB  - AIMS: To investigate the association of the complement factor H (CFH) and
      complement component 1 inhibitor (SERPING1) genes with anterior uveitis (AU).
      METHODS: A total of 406 subjects (98 patients with AU and 308 controls) were
      recruited for this study. Two CFH polymorphisms (rs3753394 and rs1065489) and two
      SERPING1 polymorphisms (rs1005511 and rs3824988) were genotyped using TaqMan
      genotyping assays. Analyses were stratified for gender and human leukocyte
      antigen (HLA)-B27 status. Correlations of the genotypes with multiple clinical
      features were also evaluated. RESULTS: No significant association was found
      between any of the four polymorphisms and AU after multiple testing corrections.
      However, stratified analyses showed that there were significant increases in the
      frequencies of T allele and TT homozygosity for CFH-rs1065489 in female patients
      compared with that of controls (pcorr=0.004 and pcorr=0.012 respectively). In
      addition, CFH-rs1065489 was also associated with AU in patients who were HLA-B27
      positive. No significant association with AU was found for the other three single
      nucleotide polymorphisms (SNPs), even stratified by gender or HLA-B27 status.
      Genotype-phenotype analyses found that CFH-rs1065489 TT genotype was associated
      with higher uveitis recurrence frequency. No correlation was found between CFH
      rs1065489 and other clinical features. CONCLUSIONS: This study revealed an
      association of CFH-rs1065489 with AU as well as uveitis recurrence frequency. The
      influence on AU could be gender specific and dependent on HLA-B27 status. Our
      results also suggested that SERPING1 does not play a significant role in the
      development of AU.

PMID- 23966371
TI  - Use of optical coherence tomography in predicting post-treatment visual outcome
      in anterior visual pathway meningiomas.
AB  - PURPOSE: To determine the prognostic value of pretreatment optical coherence
      tomography (OCT) measurement of the peripapillary retinal nerve fibre layer
      (PRNFL) in final visual outcomes of patients with anterior visual pathway
      meningioma and optic neuropathy. METHODS: Retrospective case series from a
      tertiary care academic referral centre. Fourteen eyes (12 patients) in which
      pretreatment and post-treatment OCT, visual field and comprehensive neuro
      ophthalmic exam data were available were evaluated for visual acuity, colour
      vision and visual field change after neurosurgical and/or radiation oncologic
      treatment. RESULTS: Twelve patients and 14 eyes were analysed. Patients had
      tumours centred at the tuberculum sella (3), planum sphenoidale (3), anterior
      clinoid (2), optic nerve sheath (2), sphenoid wing (2) and olfactory groove (1).
      Nine eyes had normal PRNFL thickness (mean 95.5 MUm+/- 11.0), whereas five eyes
      had thin PRNFL (mean 66.0 MUm +/- 14.2). The mean duration of follow-up was 9.7
      months. There was no significant difference in age, duration of symptoms or
      duration of follow-up between both groups (p=0.22). After treatment, the normal
      PRNFL group experienced significant improvement in the visual acuity (p=0.03),
      colour vision (p=0.016), perimetric mean deviation (p=0.019) and foveal threshold
      (p=0.016) but not pattern SD (p=0.074) compared with the group with thin PRNFL.
      On multivariate analysis, duration of symptoms, but neither age nor follow-up
      duration, predicted final visual outcome. CONCLUSIONS: Patients with compressive
      optic neuropathy due to anterior pathway meningiomas are more likely to improve
      post-treatment if they have a normal pretreatment PRNFL and shorter duration of
      symptoms.

PMID- 23966372
TI  - The relationship between visual acuity and central visual field sensitivity in
      advanced glaucoma.

PMID- 23966373
TI  - A cautious approach to interpreting retrospective data.

PMID- 23966374
TI  - Standardised disturbance of the optical coherence tomography signal has varying
      effects on the scan quality assessment when comparing four devices.

PMID- 23966375
TI  - Multiplanar 3D ultrasound imaging to assess the anatomy of the upper airway and
      measure the subglottic and tracheal diameters in adults.
AB  - OBJECTIVE: To evaluate the feasibility of using three-dimensional (3D) ultrasound
      to assess the anatomy of the airway. METHODS: 11 young volunteers were recruited
      for 3D ultrasound and MRI of the airway. 3D ultrasound data were obtained from
      the level of the true vocal cords, cricoid cartilage and upper trachea.
      Multiplanar 3D ultrasound images were rendered and compared visually with
      corresponding MRI and cadaver anatomical sections. The anteroposterior (AP) and
      transverse diameter of the subglottic space and transverse diameter of the upper
      trachea were also measured in the 3D ultrasound and MR images and compared.
      RESULTS: The airway anatomy was clearly delineated in the multiplanar 3D
      ultrasound images. It was also possible to identify the cricothyroid junction,
      and a simple method to measure the AP diameter of the subglottic space using this
      landmark is described. We were also able to accurately measure the transverse
      diameter of the upper trachea, but the transverse diameter of the subglottic
      space was overestimated using ultrasound. There was a strong correlation for the
      AP diameter measurement (r=0.94, p<0.05) and moderate correlation for the
      transverse diameter measurement (r=0.82, p=0.002) of the subglottic space, and a
      strong correlation for the transverse diameter measurement (r=0.91, p<0.05) of
      the upper trachea, in the ultrasound and MR images. CONCLUSION: The anatomy of
      the adult airway can be assessed using 3D ultrasound. It can also be used to
      accurately measure the AP diameter of the subglottic space and the transverse
      diameter of the upper trachea. ADVANCES IN KNOWLEDGE: This is the first report to
      describe the use of 3D ultrasound to evaluate the anatomy of the upper airway and
      accurately measure the AP diameter of the subglottic space and the transverse
      diameter of the upper trachea.

PMID- 23966376
TI  - Multidetector CT findings in patients with mesenteric ischaemia following
      cardiopulmonary bypass surgery.
AB  - OBJECTIVE: To investigate CT findings in patients with pathologically proven
      mesenteric ischaemia post-cardiopulmonary bypass surgery and compare them with
      the control group of patients without ischaemia. METHODS: 68 patients were
      identified by a search of local surgical and pathological databases; these
      patients met the inclusion criteria of a laparotomy within 1 month of a procedure
      requiring cardiopulmonary bypass and a CT abdomen/pelvis within 1 week of the
      pathological diagnosis. Two radiologists independently reviewed the studies,
      evaluating 17 separate findings relating to the bowel, the vasculature or other
      structures; consensus was subsequently reached. The diagnostic value of CT
      findings was assessed using logistic regression. RESULTS: 52 of 68 patients had
      pathologically proven ischaemia. Portal venous gas, mesenteric venous gas and
      small bowel faeces sign all had specificities of >0.94 for ischaemia but low
      sensitivity (<0.27). Differential mural enhancement had high sensitivity (0.92)
      but poor specificity (0.50). The combination of pneumatosis, bowel loop
      dilatation and differential mural enhancement predicted bowel ischaemia with a
      probability of 98%. The hardest signs to interpret based on poor interreader
      kappa agreement were bowel wall thinning, mesenteric stranding and differential
      mural enhancement. CONCLUSION: A combination of CT signs was predictive of
      ischaemic bowel; however, the more specific findings lacked sensitivity. If
      clinical suspicion is high for bowel ischaemia, prompt surgical intervention is
      warranted, regardless of CT findings. ADVANCES IN KNOWLEDGE: Arterial occlusion
      was uncommon and venous occlusion was not present, which is supportive of a
      predominantly non-occlusive aetiology for ischaemia in this patient group.

PMID- 23966379
TI  - Use of hydralazine-isosorbide dinitrate combination in African American and other
      race/ethnic group patients with heart failure and reduced left ventricular
      ejection fraction.
AB  - BACKGROUND: Hydralazine-isosorbide dinitrate (H-ISDN) therapy is recommended for
      African American patients with moderate to severe heart failure with reduced
      ejection fraction (<40%) (HFrEF), but use, temporal trends, and clinical
      characteristics associated with H-ISDN therapy in clinical practice are unknown.
      METHODS AND RESULTS: An observational analysis of 54 622 patients admitted with
      HFrEF and discharged home from 207 hospitals participating in the Get With The
      Guidelines-Heart Failure registry from April 2008 to March 2012 was conducted to
      assess prescription, trends, and predictors of use of H-ISDN among eligible
      patients. Among 11 185 African American patients eligible for H-ISDN therapy,
      only 2500 (22.4%) received H-ISDN therapy at discharge. In the overall eligible
      population, 5115 of 43 498 (12.6%) received H-ISDN at discharge. Treatment rates
      increased over the study period from 16% to 24% among African Americans and from
      10% to 13% among the entire HFrEF population. In a multivariable model, factors
      associated with H-ISDN use among the entire cohort included younger age; male
      sex; African American/Hispanic ethnicity; and history of diabetes, hypertension,
      anemia, renal insufficiency, higher systolic blood pressure, and lower heart
      rate. In African American patients, these factors were similar; in addition,
      being uninsured was associated with lower use. CONCLUSIONS: Overall, few
      potentially eligible patients with HFrEF are treated with H-ISDN, and among
      African-Americans fewer than one-fourth of eligible patients received guideline
      recommended H-ISDN therapy. Improved ways to facilitate use of H-ISDN therapy in
      African American patients with HFrEF are needed.

PMID- 23966380
TI  - Generation of multiple replication-competent retroviruses through recombination
      between PreXMRV-1 and PreXMRV-2.
AB  - We previously identified two novel endogenous murine leukemia virus proviruses,
      PreXMRV-1 and PreXMRV-2, and showed that they most likely recombined during
      xenograft passaging of a human prostate tumor in mice to generate xenotropic
      murine leukemia virus-related virus (XMRV). To determine the recombination
      potential of PreXMRV-1 and PreXMRV-2, we examined the generation of replication
      competent retroviruses (RCRs) over time in a cell culture system. We observed
      that either virus alone was noninfectious and the RNA transcripts of the viruses
      were undetectable in the blood and spleen of nude mice that carry them. To
      determine their potential to generate RCRs through recombination, we transfected
      PreXMRV-1 and PreXMRV-2 into 293T cells and used the virus produced to infect
      fresh cells; the presence of reverse transcriptase activity at 10 days
      postinfection indicated the presence of RCRs. Population sequencing of proviral
      DNA indicated that all RCRs contained the gag and 5' half of pol from PreXMRV-2
      and the long terminal repeat, 3' half of pol (including integrase), and env from
      PreXMRV-1. All crossovers were within sequences of at least 9 identical
      nucleotides, and crossovers within each of two selected recombination zones of
      415 nucleotides (nt) in the 5' untranslated region and 982 nt in pol were
      required to generate RCRs. A recombinant with the same genotype as XMRV was not
      detected, and our analysis indicates that the probability of generating an
      identical RCR is vanishingly small. In addition, the studies indicate that the
      process of RCR formation is primarily driven by selection for viable cis and
      trans elements from the parental proviruses. 

PMID- 23966381
TI  - Fecal influenza in mammals: selection of novel variants.
AB  - In aquatic birds, influenza A viruses mainly replicate in the intestinal tract
      without significantly affecting the health of the host, but in mammals, they
      replicate in the respiratory tract and often cause disease. Occasionally,
      influenza viruses have been detected in stool samples of hospitalized patients
      and in rectal swabs of naturally or experimentally infected mammals. In this
      study, we compared the biological and molecular differences among four wild-type
      avian H1N1 influenza viruses and their corresponding fecal and lung isolates in
      DBA/2J and BALB/cJ mice. All fecal and lung isolates were more pathogenic than
      the original wild-type viruses, when inoculated into mice of both strains. The
      increased virulence was associated with the acquisition of genetic mutations.
      Most of the novel genotypes emerged as PB2(E627K), HA(F128V), HA(F454L), or
      HA(H300P) variations, and double mutations frequently occurred in the same
      isolate. However, influenza virus strain- and host-specific differences were also
      observed in terms of selected variants. The avian H1N1 virus of shorebird origin
      appeared to be unique in its ability to rapidly adapt to BALB/cJ mice via the
      fecal route, compared to the adaptability of the H1N1 virus of mallard origin.
      Furthermore, a bimodal distribution in fecal shedding was observed in mice
      infected with the fecal isolates, while a normal distribution was observed after
      infection with the lung isolates or wild-type virus. Fecal isolates contained HA
      mutations that increased the activation pH of the HA protein. We conclude that
      influenza virus variants that emerge in fecal isolates in mammals might influence
      viral transmission, adaptation to mammals, and viral ecology or evolution. 

PMID- 23966382
TI  - Restriction of virus infection but not catalytic dNTPase activity is regulated by
      phosphorylation of SAMHD1.
AB  - SAMHD1 is a host protein responsible, at least in part, for the inefficient
      infection of dendritic, myeloid, and resting T cells by HIV-1. Interestingly, HIV
      2 and SIVsm viruses are able to counteract SAMHD1 by targeting it for proteasomal
      degradation using their Vpx proteins. It has been proposed that SAMHD1 is a dGTP
      dependent deoxynucleoside triphosphohydrolase (dNTPase) that restricts HIV-1 by
      reducing cellular dNTP levels to below that required for reverse transcription.
      However, nothing is known about SAMHD1 posttranslational modifications and their
      potential role in regulating SAMHD1 function. We used (32)P labeling and
      immunoblotting with phospho-specific antibodies to identify SAMHD1 as a
      phosphoprotein. Several amino acids in SAMHD1 were identified to be sites of
      phosphorylation using direct mass spectrometry. Mutation of these residues to
      alanine to prevent phosphorylation or to glutamic acid to mimic phosphorylation
      had no effect on the nuclear localization of SAMHD1 or its sensitivity to Vpx
      mediated degradation. Furthermore, neither alanine nor glutamic acid
      substitutions had a significant effect on SAMHD1 dNTPase activity in an in vitro
      assay. Interestingly, however, we found that a T592E mutation, mimicking
      constitutive phosphorylation at a main phosphorylation site, severely affected
      the ability of SAMHD1 to restrict HIV-1 in a U937 cell-based restriction assay.
      In contrast, a T592A mutant was still capable of restricting HIV-1. These results
      indicate that SAMHD1 phosphorylation may be a negative regulator of SAMHD1
      restriction activity. This conclusion is supported by our finding that SAMHD1 is
      hyperphosphorylated in monocytoid THP-1 cells under nonrestrictive conditions. 

PMID- 23966383
TI  - Structure of the NS1 protein N-terminal origin recognition/nickase domain from
      the emerging human bocavirus.
AB  - Human bocavirus is a newly identified, globally prevalent, parvovirus that is
      associated with respiratory infection in infants and young children. Parvoviruses
      encode a large nonstructural protein 1 (NS1) that is essential for replication of
      the viral single-stranded DNA genome and DNA packaging and may play versatile
      roles in virus-host interactions. Here, we report the structure of the human
      bocavirus NS1 N-terminal domain, the first for any autonomous parvovirus. The
      structure shows an overall fold that is canonical to the histidine-hydrophobic
      histidine superfamily of nucleases, which integrates two distinct DNA-binding
      sites: (i) a positively charged region mediated by a surface hairpin (residues
      190 to 198) that is responsible for recognition of the viral origin of
      replication of the double-stranded DNA nature and (ii) the nickase active site
      that binds to the single-stranded DNA substrate for site-specific cleavage. The
      structure reveals an acidic-residue-rich subdomain that is present in bocavirus
      NS1 proteins but not in the NS1 orthologs in erythrovirus or dependovirus, which
      may mediate bocavirus-specific interaction with DNA or potential host factors.
      These results provide insights into recognition of the origin of replication and
      nicking of DNA during bocavirus genome replication. Mapping of variable amino
      acid residues of NS1s from four human bocavirus species onto the structure shows
      a scattered pattern, but the origin recognition site and the nuclease active site
      are invariable, suggesting potential targets for antivirals against this clade of
      highly diverse human viruses. 

PMID- 23966384
TI  - Signal transducer and activator of transcription 3 limits Epstein-Barr virus
      lytic activation in B lymphocytes.
AB  - Lytic activation of Epstein-Barr virus (EBV) is central to its life cycle and to
      most EBV-related diseases. However, not every EBV-infected B cell is susceptible
      to lytic activation. This lack of uniform susceptibility to lytic activation also
      directly impacts the success of viral oncolytic therapy for EBV cancers, yet
      determinants of susceptibility to lytic induction signals are not well
      understood. To determine if host factors influence susceptibility to EBV lytic
      activation, we developed a technique to separate lytic from refractory cells and
      reported that EBV lytic activation occurs preferentially in cells with lower
      levels of signal transducer and activator of transcription 3 (STAT3). Using this
      tool to detect single cells, we now extend the correlation between STAT3 and
      lytic versus refractory states to EBV-infected circulating B cells in patients
      with primary EBV infection, leading us to investigate whether STAT3 controls
      susceptibility to EBV lytic activation. In loss-of-function and gain-of-function
      studies in EBV-positive B lymphoma and lymphoblastoid cells, we found that the
      levels of functional STAT3 regulate susceptibility to EBV lytic activation. This
      prompted us to identify a pool of candidate cellular genes that might be
      regulated by STAT3 to limit EBV lytic activation. From this pool, we confirmed
      increases in transcript levels in refractory cells of a set of genes known to
      participate in transcription repression. Taken together, our findings place STAT3
      at a critical crossroads between EBV latency and lytic activation, processes
      fundamental to EBV lymphomagenesis. 

PMID- 23966385
TI  - Generation of rhesus macaque-tropic HIV-1 clones that are resistant to major anti
      HIV-1 restriction factors.
AB  - Human immunodeficiency virus type 1 (HIV-1) replication in macaque cells is
      restricted mainly by antiviral cellular APOBEC3, TRIM5alpha/TRIM5CypA, and
      tetherin proteins. For basic and clinical HIV-1/AIDS studies, efforts to
      construct macaque-tropic HIV-1 (HIV-1mt) have been made by us and others.
      Although rhesus macaques are commonly and successfully used as infection models,
      no HIV-1 derivatives suitable for in vivo rhesus research are available to date.
      In this study, to obtain novel HIV-1mt clones that are resistant to major
      restriction factors, we altered Gag and Vpu of our best HIV-1mt clone described
      previously. First, by sequence- and structure-guided mutagenesis, three amino
      acid residues in Gag-capsid (CA) (M94L/R98S/G114Q) were found to be responsible
      for viral growth enhancement in a macaque cell line. Results of in vitro
      TRIM5alpha susceptibility testing of HIV-1mt carrying these substitutions
      correlated well with the increased viral replication potential in macaque
      peripheral blood mononuclear cells (PBMCs) with different TRIM5 alleles,
      suggesting that the three amino acids in HIV-1mt CA are involved in the
      interaction with TRIM5alpha. Second, we replaced the transmembrane domain of Vpu
      of this clone with the corresponding region of simian immunodeficiency virus
      SIVgsn166 Vpu. The resultant clone, MN4/LSDQgtu, was able to antagonize macaque
      but not human tetherin, and its Vpu effectively functioned during viral
      replication in a macaque cell line. Notably, MN4/LSDQgtu grew comparably to
      SIVmac239 and much better than any of our other HIV-1mt clones in rhesus macaque
      PBMCs. In sum, MN4/LSDQgtu is the first HIV-1 derivative that exhibits resistance
      to the major restriction factors in rhesus macaque cells. 

PMID- 23966386
TI  - A specific population of abnormal prion protein aggregates is preferentially
      taken up by cells and disaggregated in a strain-dependent manner.
AB  - Prion diseases are characterized by the conversion of the soluble protease
      sensitive host-encoded prion protein (PrP(C)) into its aggregated, protease
      resistant, and infectious isoform (PrP(Sc)). One of the earliest events occurring
      in cells following exposure to an exogenous source of prions is the cellular
      uptake of PrP(Sc). It is unclear how the biochemical properties of PrP(Sc)
      influence its uptake, although aggregate size is thought to be important. Here we
      show that for two different strains of mouse prions, one that infects cells (22L)
      and one that does not (87V), a fraction of PrP(Sc) associated with distinct
      sedimentation properties is preferentially taken up by the cells. However, while
      the fraction of PrP(Sc) and the kinetics of uptake were similar for both strains,
      PrP(Sc) derived from the 87V strain was disaggregated more rapidly than that
      derived from 22L. The increased rate of PrP(Sc) disaggregation did not correlate
      with either the conformational or aggregate stability of 87V PrP(Sc), both of
      which were greater than those of 22L PrP(Sc). Our data suggest that the kinetics
      of disaggregation of PrP(Sc) following cellular uptake is independent of PrP(Sc)
      stability but may be dependent upon some component of the PrP(Sc) aggregate other
      than PrP. Rapid disaggregation of 87V PrP(Sc) by the cell may contribute, at
      least in part, to the inability of 87V to infect cells in vitro. 

PMID- 23966387
TI  - Multiple heparan sulfate binding site engagements are required for the infectious
      entry of human papillomavirus type 16.
AB  - Human papillomavirus (HPV) entry is accompanied by multiple receptor-induced
      conformational changes (CCs) affecting both the major and minor capsid proteins,
      L1 and L2. Interaction of heparan sulfate (HS) with L1 is essential for
      successful HPV16 entry. Recently, cocrystallization of HPV16 with heparin
      revealed four distinct binding sites. Here we characterize mutant HPV16 to
      delineate the role of engagement with HS binding sites during infectious
      internalization. Site 1 (Lys278, Lys361), which mediates primary binding, is
      sufficient to trigger an L2 CC, exposing the amino terminus. Site 2 (Lys54,
      Lys356) and site 3 (Asn57, Lys59, Lys442, Lys443) are engaged following primary
      attachment and are required for infectious entry. Site 2 mutant particles are
      efficiently internalized but fail to undergo an L1 CC on the cell surface and
      subsequent uncoating in the endocytic compartment. After initial attachment to
      the cell, site 3 mutants undergo L1 and L2 CCs and then accumulate on the
      extracellular matrix (ECM). We conclude that the induction of CCs following site
      1 and site 2 interactions results in reduced affinity for the primary HS binding
      site(s) on the cell surface, which allows engagement with site 3. Taken together,
      our findings suggest that HS binding site engagement induces CCs that prepare the
      virus for downstream events, such as the exposure of secondary binding sites,
      CCs, transfer to the uptake receptor, and uncoating. 

PMID- 23966388
TI  - Maturation-associated destabilization of hepatitis B virus nucleocapsid.
AB  - The mature nucleocapsid (NC) of hepatitis B virus containing the relaxed circular
      (RC) DNA genome can be secreted extracellularly as virions after envelopment with
      the viral surface proteins or, alternatively, can be disassembled to release RC
      DNA (i.e., uncoating) into the host cell nucleus to form the covalently closed
      circular (CCC) DNA, which sustains viral replication and persistence. In
      contrast, immature NCs containing the viral single-stranded DNA or the pregenomic
      RNA are incompetent for either envelopment or uncoating. Little is currently
      known about how mature NCs, and not the immature ones, are specifically selected
      for these processes. Here, we have carried out a biochemical analysis of the
      different NC populations upon their separation through sucrose gradient
      centrifugation. We have found that the maturation of NCs is associated with their
      destabilization, manifested as increased protease and nuclease sensitivity,
      altered sedimentation during sucrose gradient centrifugation, and retarded
      mobility during native agarose gel electrophoresis. Also, three distinct
      populations of intracellular mature NCs could be differentiated based on these
      characteristics. Furthermore, mature NCs generated in vitro under cell-free
      conditions acquired similar properties. These results have thus revealed
      significant structural changes associated with NC maturation that likely play a
      role in the selective uncoating of the mature NC for CCC DNA formation and/or its
      preferential envelopment for virion secretion. 

PMID- 23966389
TI  - A functional interaction between gp41 and gp120 is observed for monomeric but not
      oligomeric, uncleaved HIV-1 Env gp140.
AB  - The envelope glycoprotein (Env) is the sole antigenic feature on the surface of
      HIV and the target for the humoral immune system. Soluble, uncleaved gp140 Env
      constructs truncated at the transmembrane domain are being investigated
      intensively as potential vaccine immunogens by many groups, and understanding
      their structural properties is essential. We used hydrogen/deuterium-exchange
      mass spectrometry and small-angle X-ray scattering to probe structural order in a
      panel of commonly used gp140 constructs and matched gp120 monomers. We observed
      that oligomeric forms of uncleaved gp140, generally presumed to be trimeric,
      contain a protease-resistant form of gp41 akin to the postfusion, helical bundle
      conformation and appear to lack specific interactions between gp120 and gp41. In
      contrast, the monomeric form of gp140 shows significant stabilization of the
      gp120 inner domain imparted by the gp41 region, demonstrating excellent agreement
      with past mutagenesis studies. Moreover, the gp140 monomers respond to CD4
      binding in manner that is consistent with the initial stages of Env activation:
      CD4 binding induces structural ordering throughout gp120 while loosening its
      association with gp41. The results indicate that uncleaved gp140 oligomers do not
      represent an authentic prefusion form of Env, whereas gp140 monomers isolated
      from the same glycoprotein preparations in many ways exhibit function and
      internal structural order that are consistent with expectations for certain
      aspects of native Env. gp140 monomers may thus be a useful reagent for advancing
      structural and functional studies. 

PMID- 23966391
TI  - Dynamics of cytokine/chemokine responses in intestinal CD4+ and CD8+ T Cells
      during Acute Simian Immunodeficiency Virus Infection.
AB  - Loss of intestinal CD4(+) T cells was associated with decreased production of
      several T-helper 1 (TH1) and TH2 cytokines and increased production of
      interleukin 17 (IL-17), gamma interferon (IFN-gamma), CCL4, and granulocyte
      macrophage colony-stimulating factor (GM-CSF) by CD8(+) T cells 21 days after
      simian immunodeficiency virus (SIV) infection in rhesus macaques. Shifting of
      mucosal TH1 to TH2 or T-cytotoxic 1 (TC1) to TC2 cytokine profiles was not
      evident. Additionally, both CD4(+) and CD8(+) T cells showed upregulation of
      macrophage migration inhibition factor (MIF) and basic fibroblast growth factor
      (FGF-basic) cytokines that have been linked to HIV disease progression. 

PMID- 23966390
TI  - Pattern recognition receptor MDA5 modulates CD8+ T cell-dependent clearance of
      West Nile virus from the central nervous system.
AB  - Many viruses induce type I interferon responses by activating cytoplasmic RNA
      sensors, including the RIG-I-like receptors (RLRs). Although two members of the
      RLR family, RIG-I and MDA5, have been implicated in host control of virus
      infection, the relative role of each RLR in restricting pathogenesis in vivo
      remains unclear. Recent studies have demonstrated that MAVS, the adaptor central
      to RLR signaling, is required to trigger innate immune defenses and program
      adaptive immune responses, which together restrict West Nile virus (WNV)
      infection in vivo. In this study, we examined the specific contribution of MDA5
      in controlling WNV in animals. MDA5(-/-) mice exhibited enhanced susceptibility,
      as characterized by reduced survival and elevated viral burden in the central
      nervous system (CNS) at late times after infection, even though small effects on
      systemic type I interferon response or viral replication were observed in
      peripheral tissues. Intracranial inoculation studies and infection experiments
      with primary neurons ex vivo revealed that an absence of MDA5 did not impact
      viral infection in neurons directly. Rather, subtle defects were observed in CNS
      specific CD8(+) T cells in MDA5(-/-) mice. Adoptive transfer into recipient
      MDA5(+/+) mice established that a non-cell-autonomous deficiency of MDA5 was
      associated with functional defects in CD8(+) T cells, which resulted in a failure
      to clear WNV efficiently from CNS tissues. Our studies suggest that MDA5 in the
      immune priming environment shapes optimal CD8(+) T cell activation and subsequent
      clearance of WNV from the CNS. 

PMID- 23966392
TI  - Latency locus complements MicroRNA 155 deficiency in vivo.
AB  - MicroRNA-155 (miR-155) is expressed in many cancers. It also executes
      evolutionary conserved functions in normal B cell development. We show that the
      Kaposi's sarcoma-associated herpesvirus (KSHV) latency locus, which contains an
      ortholog of miR-155, miR-K12-11, complements B cell deficiencies in miR-155
      knockout mice. Germinal center (GC) formation was rescued in spleen, lymph node,
      and Peyer's patches. Immunoglobulin levels were restored. This demonstrates that
      KSHV can complement the normal, physiological function of miR-155. 

PMID- 23966393
TI  - The role of interleukin-6 in the expression of PD-1 and PDL-1 on central nervous
      system cells following infection with Theiler's murine encephalomyelitis virus.
AB  - Infection with Theiler's murine encephalomyelitis virus (TMEV) in the central
      nervous system (CNS) of susceptible mice results in an immune-mediated
      demyelinating disease which is considered a relevant viral model of human
      multiple sclerosis. We previously demonstrated that the expression of positive
      costimulatory molecules (CD40, CD80, and CD86) is higher on the microglia of TMEV
      resistant C57BL/6 (B6) mice than the microglia of TMEV-susceptible SJL/J (SJL)
      mice. In this study, we analyzed the expression levels of the negative
      costimulatory molecules PD-1 and PDL-1 in the CNS of TMEV-infected SJL mice and
      B6 mice. Our results indicated that TMEV infection induces the expression of both
      PD-1 and PDL-1 on microglia and macrophages in the CNS but not in the periphery.
      The expression of PD-1 only on CNS-infiltrating macrophages and not on resident
      microglia was considerably higher (>4-fold) in TMEV-infected SJL mice than TMEV
      infected B6 mice. We further demonstrated that interleukn-6 (IL-6) is necessary
      to induce the maximal expression of PDL-1 but not PD-1 after TMEV infection using
      IL-6-deficient mice and IL-6-transgenic mice in conjunction with recombinant IL
      6. In addition, cells from type I interferon (IFN) receptor knockout mice failed
      to upregulate PD-1 and PDL-1 expression after TMEV infection in vitro, indicating
      that type I IFN signaling is associated with the upregulation. However, other IFN
      signaling may also participate in the upregulation. Taken together, these results
      strongly suggest that the expression of PD-1 and PDL-1 in the CNS is primarily
      upregulated following TMEV infection via type I IFN signaling and the maximal
      expression of PDL-1 additionally requires IL-6 signaling. 

PMID- 23966394
TI  - Effects of cellular activation on anti-HIV-1 restriction factor expression
      profile in primary cells.
AB  - Expression of cell-intrinsic antiviral factors suppresses HIV-1 replication. We
      hypothesized that cellular activation modulates host restriction and
      susceptibility to HIV-1 infection. We measured the gene expression of 34
      antiviral factors in healthy peripheral blood mononuclear cells (PBMC). Cellular
      activation induced expression of interferon-stimulated gene 15 (ISG15),
      tripartite motif 5alpha (TRIM5alpha), bone marrow stromal cell antigen 2 (BST
      2)/tetherin, and certain apolipoprotein B mRNA editing enzyme 3 (APOBEC3) family
      members. Expression of RTF1, RNA polymerase II-associated factor 1 (PAF1),
      TRIM11, TRIM26, and BST-2/tetherin correlated with decreased HIV-1 infectivity.
      This report demonstrates synchronous effects of activation-induced antiviral
      genes on HIV-1 infectivity, providing candidates for pharmacological
      manipulation. 

PMID- 23966395
TI  - The essential, nonredundant roles of RIG-I and MDA5 in detecting and controlling
      West Nile virus infection.
AB  - Virus recognition and response by the innate immune system are critical
      components of host defense against infection. Activation of cell-intrinsic
      immunity and optimal priming of adaptive immunity against West Nile virus (WNV),
      an emerging vector-borne virus, depend on recognition by RIG-I and MDA5, two
      cytosolic pattern recognition receptors (PRRs) of the RIG-I-like receptor (RLR)
      protein family that recognize viral RNA and activate defense programs that
      suppress infection. We evaluated the individual functions of RIG-I and MDA5 both
      in vitro and in vivo in pathogen recognition and control of WNV. Lack of RIG-I or
      MDA5 alone results in decreased innate immune signaling and virus control in
      primary cells in vitro and increased mortality in mice. We also generated RIG-I(
      /-) * MDA5(-/-) double-knockout mice and found that a lack of both RLRs results
      in a complete absence of innate immune gene induction in target cells of WNV
      infection and a severe pathogenesis during infection in vivo, similar to findings
      for animals lacking MAVS, the central adaptor molecule for RLR signaling. We also
      found that RNA products from WNV-infected cells but not incoming virion RNA
      display at least two distinct pathogen-associated molecular patterns (PAMPs)
      containing 5' triphosphate and double-stranded RNA that are temporally
      distributed and sensed by RIG-I and MDA5 during infection. Thus, RIG-I and MDA5
      are essential PRRs that recognize distinct PAMPs that accumulate during WNV
      replication. Collectively, these experiments highlight the necessity and function
      of multiple related, cytoplasmic host sensors in orchestrating an effective
      immune response against an acute viral infection. 

PMID- 23966396
TI  - Varicella-zoster virus open reading frame 48 encodes an active nuclease.
AB  - Based on a DNA sequence and relative genomic position similar to those other
      herpesviruses, varicella-zoster virus (VZV) open reading frame 48 (ORF48) is
      predicted to encode an alkaline nuclease. Here we report the cloning, expression,
      purification, and characterization of recombinant VZV ORF48 protein and a VZV
      ORF48 point mutation (T172P). Protein encoded by wild-type ORF48, but not mutant
      protein, displayed both endo- and exonuclease activity, identifying ORF48 as a
      potential therapeutic target in VZV disease since efficient viral replication
      requires viral nuclease activity. 

PMID- 23966397
TI  - Inhibition of megakaryocyte development in the bone marrow underlies dengue virus
      induced thrombocytopenia in humanized mice.
AB  - A characteristic clinical feature of dengue virus infection is thrombocytopenia,
      though its underlying mechanism is not definitively determined. By adoptive
      transfer of human CD34(+) fetal liver cells into immunodeficient mice, we have
      constructed humanized mice with significant levels of human platelets,
      monocytes/macrophages, and hepatocytes. Infection of these mice with both lab
      adapted and clinical strains of dengue virus induces characteristic human
      hematological changes, including transient leukopenia and thrombocytopenia. We
      show that the specific depletion of human platelets is not mediated by antibodies
      in the periphery or reduced production of human thrombopoietin in the liver but
      reduction of human megakaryocytes and megakaryocyte progenitors in the bone
      marrow of the infected mice. These findings identify inhibition of platelet
      production in the bone marrow as a key mechanism underlying dengue-induced
      thrombocytopenia and suggest the utility of the improved humanized mouse model in
      studying dengue virus infection and pathogenesis in a human cell context. 

PMID- 23966398
TI  - Defining the interaction of HIV-1 with the mucosal barriers of the female
      reproductive tract.
AB  - Worldwide, HIV-1 infects millions of people annually, the majority of whom are
      women. To establish infection in the female reproductive tract (FRT), HIV-1 in
      male ejaculate must overcome numerous innate and adaptive immune factors,
      traverse the genital epithelium, and establish infection in underlying CD4(+)
      target cells. How the virus achieves this remains poorly defined. By utilizing a
      new technique, we define how HIV-1 interacts with different tissues of the FRT
      using human cervical explants and in vivo exposure in the rhesus macaque vaginal
      transmission model. Despite previous claims of the squamous epithelium being an
      efficient barrier to virus entry, we reveal that HIV-1 can penetrate both intact
      columnar and squamous epithelial barriers to depths where the virus can encounter
      potential target cells. In the squamous epithelium, we identify virus entry
      occurring through diffusive percolation, penetrating areas where cell junctions
      are absent. In the columnar epithelium, we illustrate that virus does not
      transverse barriers as well as previously thought due to mucus impediment. We
      also show a statistically significant correlation between the viral load of
      inocula and the ability of HIV-1 to pervade the squamous barrier. Overall, our
      results suggest a diffusive percolation mechanism for the initial events of HIV-1
      entry. With these data, we also mathematically extrapolate the number of HIV-1
      particles that penetrate the mucosa per coital act, providing a biological
      description of the mechanism for HIV-1 transmission during the acute and chronic
      stages of infection. 

PMID- 23966399
TI  - TMPRSS2 is an activating protease for respiratory parainfluenza viruses.
AB  - Here, we show that human parainfluenza viruses and Sendai virus (SeV), like other
      respiratory viruses, use TMPRSS2 for their activation. The membrane fusion
      proteins of respiratory viruses often possess serine and glutamine residues at
      the P2 and P3 positions, respectively, but these residues were not critical for
      cleavage by TMPRSS2. However, mutations of these residues affected SeV growth in
      specific epithelial cell lines, suggesting the importance of these residues for
      SeV replication in epithelia. 

PMID- 23966400
TI  - Processing of the VP1/2A junction is not necessary for production of foot-and
      mouth disease virus empty capsids and infectious viruses: characterization of
      "self-tagged" particles.
AB  - The foot-and-mouth disease virus (FMDV) capsid protein precursor, P1-2A, is
      cleaved by 3C(pro) to generate VP0, VP3, VP1, and the peptide 2A. The capsid
      proteins self-assemble into empty capsid particles or viruses which do not
      contain 2A. In a cell culture-adapted strain of FMDV (O1 Manisa [Lindholm]),
      three different amino acid substitutions (E83K, S134C, and K210E) were identified
      within the VP1 region of the P1-2A precursor compared to the field strain (wild
      type [wt]). Expression of the O1 Manisa P1-2A (wt or with the S134C substitution
      in VP1) plus 3C(pro), using a transient expression system, resulted in efficient
      capsid protein production and self-assembly of empty capsid particles. Removal of
      the 2A peptide from the capsid protein precursor had no effect on capsid protein
      processing or particle assembly. However, modification of E83K alone abrogated
      particle assembly with no apparent effect on protein processing. Interestingly,
      the K210E substitution, close to the VP1/2A junction, completely blocked
      processing by 3C(pro) at this cleavage site, but efficient assembly of "self
      tagged" empty capsid particles, containing the uncleaved VP1-2A, was observed.
      These self-tagged particles behaved like the unmodified empty capsids in antigen
      enzyme-linked immunosorbent assays and integrin receptor binding assays.
      Furthermore, mutant viruses with uncleaved VP1-2A could be rescued in cells from
      full-length FMDV RNA transcripts encoding the K210E substitution in VP1. Thus,
      cleavage of the VP1/2A junction is not essential for virus viability. The
      production of such engineered self-tagged empty capsid particles may facilitate
      their purification for use as diagnostic reagents and vaccines. 

PMID- 23966401
TI  - Human cytomegalovirus UL76 elicits novel aggresome formation via interaction with
      S5a of the ubiquitin proteasome system.
AB  - HCMV UL76 is a member of a conserved Herpesviridae protein family (Herpes_UL24)
      that is involved in viral production, latency, and reactivation. UL76 presents as
      globular aggresomes in the nuclei of transiently transfected cells. Bioinformatic
      analyses predict that UL76 has a propensity for aggregation and targets cellular
      proteins implicated in protein folding and ubiquitin-proteasome systems (UPS).
      Furthermore, fluorescence recovery after photobleaching experiments suggests that
      UL76 reduces protein mobility in the aggresome, which indicates that UL76 elicits
      the aggregation of misfolded proteins. Moreover, in the absence of other viral
      proteins, UL76 interacts with S5a, which is a major receptor of polyubiquitinated
      proteins for UPS proteolysis via its conserved region and the von Willebrand
      factor type A (VWA) domain of S5a. We demonstrate that UL76 sequesters
      polyubiquitinated proteins and S5a to nuclear aggresomes in biological proximity.
      After knockdown of endogenous S5a by RNA interference techniques, the UL76 level
      was only minimally affected in transiently expressing cells. However, a
      significant reduction in the number of cells containing UL76 nuclear aggresomes
      was observed, which suggests that S5a may play a key role in aggresome formation.
      Moreover, we show that UL76 interacts with S5a in the late phase of viral
      infection and that knockdown of S5a hinders the development of both the
      replication compartment and the aggresome. In this study, we demonstrate that
      UL76 induces a novel nuclear aggresome, likely by subverting S5a of the UPS.
      Given that UL76 belongs to a conserved family, this underlying mechanism may be
      shared by all members of the Herpesviridae. 

PMID- 23966402
TI  - Refrex-1, a soluble restriction factor against feline endogenous and exogenous
      retroviruses.
AB  - The host defense against viral infection is acquired during the coevolution or
      symbiosis of the host and pathogen. Several cellular factors that restrict
      retroviral infection have been identified in the hosts. Feline leukemia virus
      (FeLV) is a gammaretrovirus that is classified into several receptor interference
      groups, including a novel FeLV-subgroup D (FeLV-D) that we recently identified.
      FeLV-D is generated by transduction of the env gene of feline endogenous
      gammaretrovirus of the domestic cat (ERV-DCs) into FeLV. Some ERV-DCs are
      replication competent viruses which are present and hereditary in cats. We report
      here the determination of new viral receptor interference groups and the
      discovery of a soluble antiretroviral factor, termed Refrex-1. Detailed analysis
      of FeLV-D strains and ERV-DCs showed two receptor interference groups that are
      distinct from other FeLV subgroups, and Refrex-1 specifically inhibited one of
      them. Refrex-1 is characterized as a truncated envelope protein of ERV-DC and
      includes the N-terminal region of surface unit, which is a putative receptor
      binding domain, but lacks the transmembrane region. Refrex-1 is efficiently
      secreted from the cells and appears to cause receptor interference
      extracellularly. Two variants of Refrex-1 encoded by provirus loci, ERV-DC7 and
      DC16, are expressed in a broad range of feline tissues. The host retains Refrex-1
      as an antiretroviral factor, which may potentially prevent reemergence of the
      ERVs and the emergence of novel ERV-related viruses in cats. Refrex-1 may have
      been acquired during endogenization of ERV-DCs and may play an important role in
      retroviral restriction and antiviral defense in cats. 

PMID- 23966403
TI  - Transmissible gastroenteritis coronavirus genome packaging signal is located at
      the 5' end of the genome and promotes viral RNA incorporation into virions in a
      replication-independent process.
AB  - Preferential RNA packaging in coronaviruses involves the recognition of viral
      genomic RNA, a crucial process for viral particle morphogenesis mediated by RNA
      specific sequences, known as packaging signals. An essential packaging signal
      component of transmissible gastroenteritis coronavirus (TGEV) has been further
      delimited to the first 598 nucleotides (nt) from the 5' end of its RNA genome, by
      using recombinant viruses transcribing subgenomic mRNA that included potential
      packaging signals. The integrity of the entire sequence domain was necessary
      because deletion of any of the five structural motifs defined within this region
      abrogated specific packaging of this viral RNA. One of these RNA motifs was the
      stem-loop SL5, a highly conserved motif in coronaviruses located at nucleotide
      positions 106 to 136. Partial deletion or point mutations within this motif also
      abrogated packaging. Using TGEV-derived defective minigenomes replicated in trans
      by a helper virus, we have shown that TGEV RNA packaging is a replication
      independent process. Furthermore, the last 494 nt of the genomic 3' end were not
      essential for packaging, although this region increased packaging efficiency.
      TGEV RNA sequences identified as necessary for viral genome packaging were not
      sufficient to direct packaging of a heterologous sequence derived from the green
      fluorescent protein gene. These results indicated that TGEV genome packaging is a
      complex process involving many factors in addition to the identified RNA
      packaging signal. The identification of well-defined RNA motifs within the TGEV
      RNA genome that are essential for packaging will be useful for designing
      packaging-deficient biosafe coronavirus-derived vectors and providing new targets
      for antiviral therapies. 

PMID- 23966404
TI  - Phosphorylation of measles virus nucleoprotein affects viral growth by changing
      gene expression and genomic RNA stability.
AB  - The measles virus (MV) nucleoprotein associates with the viral RNA genome to form
      the N-RNA complex, providing a template for viral RNA synthesis. In our previous
      study, major phosphorylation sites of the nucleoprotein were identified as S479
      and S510. However, the functions of these phosphorylation sites have not been
      clarified. In this study, we rescued recombinant MVs (rMVs) whose phosphorylation
      sites in the nucleoprotein were substituted (rMV-S479A, rMV-S510A, and rMV
      S479A/S510A) by reverse genetics and used them in subsequent analyses. In a one
      step growth experiment, rMVs showed rapid growth kinetics compared with wild-type
      MV, although the peak titer of the wild-type MV was the same as or slightly
      higher than those of the rMVs. Time course analysis of nucleoprotein accumulation
      also revealed that viral gene expression of rMV was enhanced during the early
      phase of infection. These findings suggest that nucleoprotein phosphorylation has
      an important role in controlling viral growth rate through the regulation of
      viral gene expression. Conversely, multistep growth curves revealed that
      nucleoprotein-phosphorylation intensity inversely correlated with viral titer at
      the plateau phase. Additionally, the phosphorylation intensity of the wild-type
      nucleoprotein in infected cells was significantly reduced through nucleoprotein
      phosphoprotein binding. Excessive nucleoprotein-phosphorylation resulted in lower
      stability against RNase and faster turnover of viral genomic RNA. These results
      suggest that nucleoprotein-phosphorylation is also involved in viral genomic RNA
      stability. 

PMID- 23966405
TI  - Gag-dependent enrichment of HIV-1 RNA near the uropod membrane of polarized T
      cells.
AB  - The enrichment of HIV-1 macromolecules at the uropod of polarized T cells can
      significantly promote virus assembly and cell-mediated infection. Using live-cell
      fluorescence microscopy, we demonstrate that full-length HIV-1 RNA is enriched at
      the uropod membrane; furthermore, the presence of HIV-1 Gag containing a
      functional nucleocapsid domain is necessary for this HIV-1 RNA enrichment. The
      results from these studies provide novel insights into the mechanism of HIV-1
      replication in polarized T cells. 

PMID- 23966406
TI  - The human adenovirus 5 L4 promoter is activated by cellular stress response
      protein p53.
AB  - During adenovirus infection, the emphasis of gene expression switches from early
      genes to late genes in a highly regulated manner. Two gene products, L4-22K and
      L4-33K, contribute to this switch by activating the major late transcription unit
      (MLTU) and regulating the splicing of its transcript. L4-22K and L4-33K
      expression is driven initially by a recently described L4 promoter (L4P) embedded
      within the MLTU that is activated by early and intermediate viral factors: E1A,
      E4 Orf3, and IVa2. Here we show that this promoter is also significantly
      activated by the cellular stress response regulator, p53. Exogenous expression of
      p53 activated L4P in reporter assays, while depletion of endogenous p53 inhibited
      the induction of L4P by viral activators. Chromatin immunoprecipitation studies
      showed that p53 associates with L4P and that during adenovirus type 5 (Ad5)
      infection, this association peaks at 12 h postinfection, coinciding with the
      phase of the infectious cycle when L4P is active, and is then lost as MLP
      activation commences. p53 activation of L4P is significant during Ad5 infection,
      since depletion of p53 prior to infection of either immortalized or normal cells
      led to severely reduced late gene expression. The association of p53 with L4P is
      transient due to the action of products of L4P activity (L4-22K/33K), which
      establish a negative feedback loop that ensures the transient activity of L4P at
      the start of the late phase and contributes to an efficient switch from early- to
      late-phase virus gene expression. 

PMID- 23966407
TI  - Uptake of rabies virus into epithelial cells by clathrin-mediated endocytosis
      depends upon actin.
AB  - Rabies virus (RABV) causes a fatal zoonotic encephalitis. Disease symptoms
      require replication and spread of the virus within neuronal cells; however, in
      infected animals as well as in cell culture the virus replicates in a broad range
      of cell types. Here we use a single-cycle RABV and a recombinant vesicular
      stomatitis virus (rVSV) in which the glycoprotein (G) was replaced with that of
      RABV (rVSV RABV G) to examine RABV uptake into the African green monkey kidney
      cell line BS-C-1. Combining biochemical studies and real-time spinning-disk
      confocal fluorescence microscopy, we show that the predominant entry pathway of
      RABV particles into BS-C-1 cells is clathrin dependent. Viral particles enter
      cells in pits with elongated structures and incomplete clathrin coats which
      depend upon actin to complete the internalization process. By measuring the time
      of internalization and the abundance of the clathrin adaptor protein AP2, we
      further show that the pits that internalize RABV particles are similar to those
      that internalize VSV particles. Pharmacological perturbations of dynamin or of
      actin polymerization inhibit productive infection, linking our observations on
      particle uptake with viral infectivity. This work extends to RABV particles the
      finding that clathrin-mediated endocytosis of rhabdoviruses proceeds through
      incompletely coated pits which depend upon actin. 

PMID- 23966408
TI  - Role of DC-SIGN in Lassa virus entry into human dendritic cells.
AB  - The arenavirus Lassa virus (LASV) causes a severe hemorrhagic fever with high
      mortality in humans. Antigen-presenting cells, in particular dendritic cells
      (DCs), are early and preferred targets of LASV, and their productive infection
      contributes to the virus-induced immunosuppression observed in fatal disease.
      Here, we characterized the role of the C-type lectin DC-specific ICAM-3-grabbing
      nonintegrin (DC-SIGN) in LASV entry into primary human DCs using a chimera of the
      prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) expressing the
      LASV glycoprotein (rLCMV-LASVGP). We found that differentiation of human primary
      monocytes into DCs enhanced virus attachment and entry, concomitant with the
      upregulation of DC-SIGN. LASV and rLCMV-LASVGP bound to DC-SIGN via mannose
      sugars located on the N-terminal GP1 subunit of LASVGP. We provide evidence that
      DC-SIGN serves as an attachment factor for rLCMV-LASVGP in monocyte-derived
      immature dendritic cells (MDDC) and can accelerate the capture of free virus.
      However, in contrast to the phlebovirus Uukuniemi virus (UUKV), which uses DC
      SIGN as an authentic entry receptor, productive infection with rLCMV-LASVGP was
      less dependent on DC-SIGN. In contrast to the DC-SIGN-mediated cell entry of
      UUKV, entry of rLCMV-LASVGP in MDDC was remarkably slow and depended on actin,
      indicating the use of different endocytotic pathways. In sum, our data reveal
      that DC-SIGN can facilitate cell entry of LASV in human MDDC but that its role
      seems distinct from the function as an authentic entry receptor reported for
      phleboviruses. 

PMID- 23966409
TI  - Global RNA structure analysis of poliovirus identifies a conserved RNA structure
      involved in viral replication and infectivity.
AB  - The genomes of RNA viruses often contain RNA structures that are crucial for
      translation and RNA replication and may play additional, uncharacterized roles
      during the viral replication cycle. For the picornavirus family member
      poliovirus, a number of functional RNA structures have been identified, but much
      of its genome, especially the open reading frame, has remained uncharacterized.
      We have now generated a global RNA structure map of the poliovirus genome using a
      chemical probing approach that interrogates RNA structure with single-nucleotide
      resolution. In combination with orthogonal evolutionary analyses, we uncover
      several conserved RNA structures in the open reading frame of the viral genome.
      To validate the ability of our global analyses to identify functionally important
      RNA structures, we further characterized one of the newly identified structures,
      located in the region encoding the RNA-dependent RNA polymerase, 3D(pol), by site
      directed mutagenesis. Our results reveal that the structure is required for viral
      replication and infectivity, since synonymous mutants are defective in these
      processes. Furthermore, these defects can be partially suppressed by mutations in
      the viral protein 3C(pro), which suggests the existence of a novel functional
      interaction between an RNA structure in the 3D(pol)-coding region and the viral
      protein(s) 3C(pro) and/or its precursor 3CD(pro). 

PMID- 23966410
TI  - Neutralizing IgG at the portal of infection mediates protection against vaginal
      simian/human immunodeficiency virus challenge.
AB  - Neutralizing antibodies may have critical importance in immunity against human
      immunodeficiency virus type 1 (HIV-1) infection. However, the amount of
      protective antibody needed at mucosal surfaces has not been fully established.
      Here, we evaluated systemic and mucosal pharmacokinetics (PK) and
      pharmacodynamics (PD) of 2F5 IgG and 2F5 Fab fragments with respect to protection
      against vaginal challenge with simian-human immunodeficiency virus-BaL in
      macaques. Antibody assessment demonstrated that 2F5 IgG was more potent than
      polymeric forms (IgM and IgA) across a range of cellular and tissue models.
      Vaginal challenge studies demonstrated a dose-dependent protection for 2F5 IgG
      and no protection with 2F5 Fab despite higher vaginal Fab levels at the time of
      challenge. Animals receiving 50 or 25 mg/kg of body weight 2F5 IgG were
      completely protected, while 3/5 animals receiving 5 mg/kg were protected. In the
      control animals, infection was established by a minimum of 1 to 4
      transmitted/founder (T/F) variants, similar to natural human infection by this
      mucosal route; in the two infected animals that had received 5 mg 2F5 IgG,
      infection was established by a single T/F variant. Serum levels of 2F5 IgG were
      more predictive of sterilizing protection than measured vaginal levels. Fc
      mediated antiviral activity did not appear to influence infection of primary
      target cells in cervical explants. However, PK studies highlighted the importance
      of the Fc portion in tissue biodistribution. Data presented in this study may be
      important in modeling serum levels of neutralizing antibodies that need to be
      achieved by either vaccination or passive infusion to prevent mucosal acquisition
      of HIV-1 infection in humans. 

PMID- 23966411
TI  - A stabilized headless measles virus attachment protein stalk efficiently triggers
      membrane fusion.
AB  - Paramyxovirus attachment and fusion (F) envelope glycoprotein complexes mediate
      membrane fusion required for viral entry. The measles virus (MeV) attachment (H)
      protein stalk domain is thought to directly engage F for fusion promotion.
      However, past attempts to generate truncated, fusion-triggering-competent H-stem
      constructs remained fruitless. In this study, we addressed the problem by testing
      the hypothesis that truncated MeV H stalks may require stabilizing
      oligomerization tags to maintain intracellular transport competence and F
      triggering activity. We engineered H-stems of different lengths with added 4
      helix bundle tetramerization domains and demonstrate restored cell surface
      expression, efficient interaction with F, and fusion promotion activity of these
      constructs. The stability of the 4-helix bundle tags and the relative
      orientations of the helical wheels of H-stems and oligomerization tags govern the
      kinetics of fusion promotion, revealing a balance between H stalk conformational
      stability and F-triggering activity. Recombinant MeV particles expressing a
      bioactive H-stem construct in the place of full-length H are viable, albeit
      severely growth impaired. Overall, we demonstrate that the MeV H stalk represents
      the effector domain for MeV F triggering. Fusion promotion appears linked to the
      conformational flexibility of the stalk, which must be tightly regulated in viral
      particles to ensure efficient virus entry. While the pathways toward assembly of
      functional fusion complexes may differ among diverse members of the paramyxovirus
      family, central elements of the triggering machinery emerge as highly conserved. 

PMID- 23966412
TI  - Nontraditional localization and retention signals localize human cytomegalovirus
      pUL34 to the nucleus.
AB  - The human cytomegalovirus (HCMV) UL34 proteins localize to the nucleus. We
      identified a 204-amino-acid region, amino acids 40 to 244, as required for
      nuclear retention. A highly conserved 12-amino-acid section, amino acids 198 to
      210, was required for nuclear localization. Although the nuclear localization and
      retention signals of pUL34 overlap the domain required for DNA-binding activity,
      the two regions are separable by point mutations. Our results presented here
      identify the first example of an HCMV protein with separable nuclear localization
      and retention signals. 

PMID- 23966413
TI  - KLRG1 negatively regulates natural killer cell functions through the Akt pathway
      in individuals with chronic hepatitis C virus infection.
AB  - In this study, we demonstrate that killer cell lectin-like receptor subfamily G
      member 1 (KLRG1), a transmembrane protein preferentially expressed on T cells, is
      highly expressed on CD56(+) NK cells, which are significantly reduced in their
      numbers and functions in the peripheral blood of patients with chronic hepatitis
      C virus (HCV) infection compared to subjects without infection. KLRG1 expression
      is also upregulated on healthy NK cells exposed to Huh-7 hepatocytes infected
      with HCV in vitro. Importantly, the expression levels of KLRG1 are inversely
      associated with the capacity of NK cells to proliferate and to produce gamma
      interferon (IFN-gamma) but positively associated with apoptosis of NK cells in
      response to inflammatory cytokine stimulation. KLRG1(+) NK cells, including
      CD56(bright) and CD56(dim) subsets, exhibit impaired cell activation and IFN
      gamma production but increased apoptosis compared to KLRG1(-) NK cells,
      particularly in HCV-infected individuals. Importantly, blockade of KLRG1
      signaling significantly recovered the impaired IFN-gamma production by NK cells
      from HCV-infected subjects. Blockade of KLRG1 also enhanced the impaired
      phosphorylation of Akt (Ser473) in NK cells from HCV-infected subjects. Taken
      together, these results indicate that KLRG1 negatively regulates NK cell numbers
      and functions via the Akt pathway, thus providing a novel marker and therapeutic
      target for HCV infection. 

PMID- 23966415
TI  - New lives for old drugs: call for ideas from cardiologists.

PMID- 23966414
TI  - Nuclear relocalization of polyadenylate binding protein during rift valley fever
      virus infection involves expression of the NSs gene.
AB  - Rift Valley fever virus (RVFV), an ambisense member of the family Bunyaviridae,
      genus Phlebovirus, is the causative agent of Rift Valley fever, an important
      zoonotic infection in Africa and the Middle East. Phlebovirus proteins are
      translated from virally transcribed mRNAs that, like host mRNA, are capped but,
      unlike host mRNAs, are not polyadenylated. Here, we investigated the role of
      PABP1 during RVFV infection of HeLa cells. Immunofluorescence studies of infected
      cells demonstrated a gross relocalization of PABP1 to the nucleus late in
      infection. Immunofluorescence microscopy studies of nuclear proteins revealed
      costaining between PABP1 and markers of nuclear speckles. PABP1 relocalization
      was sharply decreased in cells infected with a strain of RVFV lacking the gene
      encoding the RVFV nonstructural protein S (NSs). To determine whether PABP1 was
      required for RVFV infection, we measured the production of nucleocapsid protein
      (N) in cells transfected with small interfering RNAs (siRNAs) targeting PABP1. We
      found that the overall percentage of RVFV N-positive cells was not changed by
      siRNA treatment, indicating that PABP1 was not required for RVFV infection.
      However, when we analyzed populations of cells producing high versus low levels
      of PABP1, we found that the percentage of RVFV N-positive cells was decreased in
      cell populations producing physiologic levels of PABP1 and increased in cells
      with reduced levels of PABP1. Together, these results suggest that production of
      the NSs protein during RVFV infection leads to sequestration of PABP1 in the
      nuclear speckles, creating a state within the cell that favors viral protein
      production. 

PMID- 23966416
TI  - Maximal step-up height as a simple and relevant health indicator: a study of leg
      muscle strength and the associations to age, anthropometric variables, aerobic
      fitness and physical function.
AB  - BACKGROUND: Low muscle strength is related to an increased risk for several
      chronic diseases. Increased muscle strength improves daily function and quality
      of life. OBJECTIVE: To measure maximal step-up height, an assessment of leg
      strength and function, and its association to age, anthropometric variables,
      maximal oxygen uptake (VO2-max) and self-reported physical function before and
      after a physical activity programme. METHODS: Female patients (n=178, 22-83
      years) with musculoskeletal disorders, metabolic risk factors and other chronic
      diseases were recruited from primary care. Maximal step-up height (standardised
      step-up without a kick-off with the floor foot), anthropometric variables, VO2
      max and self-reported physical function (Short Form 36 (SF-36)) were assessed
      before and after a 3-month group training intervention programme. Associations
      between maximal step-up height and other variables were examined using univariate
      and multivariate methods. RESULTS: At baseline and after intervention, maximal
      step-up height was negatively correlated to age, waist circumference and body
      weight and positively correlated to VO2-max, self-reported physical function and
      height. Furthermore, maximal step-up height correlated to training intensity at
      follow-up. Variations in changes in maximal step-up height were significantly
      explained by changes in waist circumference and physical function, regardless of
      age and changes in VO2-max. Maximal step-up height below 24 cm discriminated
      patients with self-reported severe limitation in physical function. CONCLUSIONS:
      Maximal step-up height, assessed simply with a standardised step-up test, may
      function as a relevant indicator of health since it correlated negatively to the
      metabolic risk factors, waist circumference, body weight and age, and positively
      to VO2-max and physical function.

PMID- 23966417
TI  - Evidence in managing traumatic anterior shoulder instability: a scoping review.
AB  - BACKGROUND: Traumatic anterior shoulder instability (TASI) accounts for 95% of
      glenohumeral dislocations and is associated with soft tissue and bony
      pathoanatomies. Non-operative treatments include slings, bracing and
      physiotherapy. Operative treatment is common, including bony and soft-tissue
      reconstructions performed through open or arthroscopic approaches. There is
      management variation in patient pathways for TASI including when to refer and
      when to operate. METHODS: A scoping review of systematic reviews, randomised
      controlled trials, comparing operative with non-operative treatments and
      different operative treatments were the methods followed. Search was conducted
      for online bibliographic databases and reference lists of relevant articles from
      2002 to 2012. Systematic reviews were appraised using AMSTAR (assessment of
      multiple systematic reviews) criteria. Controlled trials were appraised using the
      CONSORT (consolidation of standards of reporting trials) tool. RESULTS: Analysis
      of the reviews did not offer strong evidence for a best treatment option for
      TASI. No studies directly compare open, arthroscopic and structured
      rehabilitation programmes. Evaluation of arthroscopic studies and comparison to
      open procedures was difficult, as many of the arthroscopic techniques included
      are no longer used. Recurrence rate was generally considered the best measure of
      operative success, but was poorly documented throughout all studies. There was
      conflicting evidence on the optimal timing of intervention and no consensus on
      any scoring system or outcome measure. CONCLUSIONS: There is no agreement about
      which validated outcome tool should be used for assessing shoulder instability in
      patients. There is limited evidence regarding the comparative effectiveness of
      surgical and non-surgical treatment of TASI, including a lack of evidence
      regarding the optimal timing of such treatments. There is a need for a well
      structured randomised control trial to assess the efficacy of surgical and non
      surgical interventions for this common type of shoulder instability.

PMID- 23966419
TI  - Genetic alterations in thyroid tumors from patients irradiated in childhood for
      tinea capitis treatment.
AB  - OBJECTIVE: Exposure to ionizing radiation at young age is the strongest risk
      factor for the occurrence of papillary thyroid carcinoma (PTC). RET/PTC
      rearrangements are the most frequent genetic alterations associated with
      radiation-induced PTC, whereas BRAF and RAS mutations and PAX8-PPARG
      rearrangement have been associated with sporadic PTC. We decided to search for
      such genetic alterations in PTCs of patients subjected in childhood to scalp
      irradiation. DESIGN: We studied 67 thyroid tumors from 49 individuals irradiated
      in childhood for tinea capitis scalp epilation: 36 malignant (12 cases of
      conventional PTC (cPTC), two cPTC metastases, 20 cases of follicular variant PTC
      (FVPTC), one oncocytic variant of PTC and one follicular carcinoma) and 31
      follicular thyroid adenomas. METHODS: The lesions were screened for the
      BRAF(V600E) and NRAS mutations and for RET/PTC and PAX8-PPARG rearrangements.
      RESULTS: BRAF(V600E) mutation was detected in seven of 14 (50%) cPTC and two of
      20 FVPTC (10%) (P=0.019). NRAS mutation was present in one case of FVPTC (5%).
      RET/PTC1 rearrangement was found, by RT-PCR, in one of 17 cases (5.9%) and by
      fluorescence in situ hybridization in two of six cases (33%). PAX8-PPARG
      rearrangement was not detected in any carcinoma. None of the follicular adenomas
      presented any of the aforementioned genetic alterations. CONCLUSIONS: The
      prevalence of BRAF(V600E) mutation in our series is the highest reported in
      series of PTCs arising in radiation-exposed individuals. The prevalence of
      RET/PTC1 rearrangement fits with the values recently described in a similar
      setting.

PMID- 23966420
TI  - Caloric restriction modulates Mcl-1 expression and sensitizes lymphomas to BH3
      mimetic in mice.
AB  - Caloric restriction (CR) is proposed to decrease tumorigenesis through a variety
      of mechanisms including effects on glycolysis. However, the understanding of how
      CR affects the response to cancer therapy is still rudimentary. Here, using the
      Eu-Myc transgenic mouse model of B-cell lymphoma, we report that by reducing
      protein translation, CR can reduce expression of the prosurvival Bcl-2 family
      member Mcl-1 and sensitize lymphomas to ABT-737-induced death in vivo. By using
      Eu-Myc lymphoma cells lacking p53, we showed that CR mimetics such as 2
      deoxyglucose led to a decrease in Mcl-1 expression and sensitized lymphoma cells
      to ABT-737-induced death independently of p53. In keeping with this, Eu-Myc
      lymphoma cells lacking the BH3-only proapoptotic members Noxa, Puma, or Bim were
      also sensitized by CR mimetics to ABT-737-induced death. Remarkably, neither the
      loss of both Puma and Noxa, the loss of both Puma and Bim, nor the loss of all
      three BH3-only proteins prevented sensitization to ABT-737 induced by CR
      mimetics. Thus, CR can influence Mcl-1 expression and sensitize cells to BH3
      mimetic-induced apoptosis, independently of the main BH3-only proteins and of
      p53. Exploiting this may improve the efficiency of, or prevent resistance to,
      cancer therapy. 

PMID- 23966418
TI  - Alpha-synuclein post-translational modifications as potential biomarkers for
      Parkinson disease and other synucleinopathies.
AB  - The development of novel therapies against neurodegenerative disorders requires
      the ability to detect their early, presymptomatic manifestations in order to
      enable treatment before irreversible cellular damage occurs. Precocious signs
      indicative of neurodegeneration include characteristic changes in certain protein
      levels, which can be used as diagnostic biomarkers when they can be detected in
      fluids such as blood plasma or cerebrospinal fluid. In the case of
      synucleinopathies, cerebrospinal alpha-synuclein (alpha-syn) has attracted great
      interest as a potential biomarker; however, there is ongoing debate regarding the
      association between cerebrospinal alpha-syn levels and neurodegeneration in
      Parkinson disease and synucleinopathies. Post-translational modifications (PTMs)
      have emerged as important determinants of alpha-syn's physiological and
      pathological functions. Several PTMs are enriched within Lewy bodies and exist at
      higher levels in alpha-synucleinopathy brains, suggesting that certain modified
      forms of alpha-syn might be more relevant biomarkers than the total alpha-syn
      levels. However, the quantification of PTMs in bodily fluids poses several
      challenges. This review describes the limitations of current immunoassay-based
      alpha-syn quantification methods and highlights how these limitations can be
      overcome using novel mass-spectrometry-based assays. In addition, we describe how
      advances in chemical synthesis, which have enabled the preparation of alpha-syn
      proteins that are site-specifically modified at single or multiple residues, can
      facilitate the development of more accurate assays for detecting and quantifying
      alpha-syn PTMs in health and disease. 

PMID- 23966422
TI  - Myocardial perfusion scintigraphy using rubidium-82 positron emission tomography.
AB  - INTRODUCTION: Myocardial perfusion scintigraphy (MPS) is an established non
      invasive technique for the diagnosis and management of patients with suspected or
      known coronary artery disease. Because of the wealth of prognostic data, MPS
      single photon emission computed tomography (SPECT) is the most commonly used
      functional test to detect inducible ischaemia. However, the increasing
      availability of positron emission tomography (PET) scanners for oncology along
      with the introduction of the generator-produced PET tracer rubidium-82 (82Rb) has
      helped the growth of MPS PET. SOURCES OF DATA: Relevant review articles, primary
      literature and clinical guidelines identified through medical literature search
      engines. AREAS OF AGREEMENT: PET offers advantages over SPECT, including
      increased patient throughput because of rapid scanning protocols, reduced
      radiation exposure to patients and the ability to quantify tracer distribution
      accurately and hence measure myocardial perfusion in millilitre per gram per
      minute and hence myocardial perfusion reserve (MPR). AREAS OF CONTROVERSY:
      Although PET has advantages over SPECT, there are no large-scale prognostic or
      cost-effectiveness data to support it use as the primary MPS technique. GROWING
      POINTS: A wider use of absolute measurements of perfusion has the potential to
      improve diagnostic accuracy and to add prognostic value over relative assessment
      of myocardial perfusion. AREAS TIMELY FOR DEVELOPING RESEARCH: Assessment of
      absolute myocardial perfusion may provide insight into the effects of traditional
      risk factors on perfusion reserve and the impact of risk factor modifications on
      progression of coronary artery disease.

PMID- 23966421
TI  - Does coronary CT angiography improve risk stratification over coronary calcium
      scoring in symptomatic patients with suspected coronary artery disease? Results
      from the prospective multicenter international CONFIRM registry.
AB  - AIMS: The prognostic value of coronary artery calcium (CAC) scoring is well
      established and has been suggested for use to exclude significant coronary artery
      disease (CAD) for symptomatic individuals with CAD. Contrast-enhanced coronary
      computed tomographic angiography (CCTA) is an alternative modality that enables
      direct visualization of coronary stenosis severity, extent, and distribution.
      Whether CCTA findings of CAD add an incremental prognostic value over CAC in
      symptomatic individuals has not been extensively studied. METHODS AND RESULTS: We
      prospectively identified symptomatic patients with suspected but without known
      CAD who underwent both CAC and CCTA. Symptoms were defined by the presence of
      chest pain or dyspnoea, and pre-test likelihood of obstructive CAD was assessed
      by the method of Diamond and Forrester (D-F). CAC was measured by the method of
      Agatston. CCTAs were graded for obstructive CAD (>70% stenosis); and CAD plaque
      burden, distribution, and location. Plaque burden was determined by a segment
      stenosis score (SSS), which reflects the number of coronary segments with plaque,
      weighted for stenosis severity. Plaque distribution was established by a segment
      involvement score (SIS), which reflects the number of segments with plaque
      irrespective of stenosis severity. Finally, a modified Duke prognostic index
      accounting for stenosis severity, plaque distribution, and plaque location-was
      calculated. Nested Cox proportional hazard models for a composite endpoint of all
      cause mortality and non-fatal myocardial infarction (D/MI) were employed to
      assess the incremental prognostic value of CCTA over CAC. A total of 8627
      symptomatic patients (50% men, age 56 +/- 12 years) followed for 25 months
      (interquartile range 17-40 months) comprised the study cohort. By CAC, 4860 (56%)
      and 713 (8.3%) patients had no evident calcium or a score of >400, respectively.
      By CCTA, 4294 (49.8%) and 749 (8.7%) had normal coronary arteries or obstructive
      CAD, respectively. At follow-up, 150 patients experienced D/MI. CAC improved
      discrimination beyond D-F and clinical variables (area under the receiver
      operator characteristic curve 0.781 vs. 0.788, P = 0.004). When added
      sequentially to D-F, clinical variables, and CAC, all CCTA measures of CAD
      improved discrimination of patients at risk for D/MI: obstructive CAD (0.82, P <
      0.001), SSS (0.81, P < 0.001), SIS (0.81, P = 0.003), and Duke CAD prognostic
      index (0.82, P < 0.0001). CONCLUSION: In symptomatic patients with suspected CAD,
      CCTA adds incremental discriminatory power over CAC for discrimination of
      individuals at risk of death or MI.

PMID- 23966423
TI  - Genetic generations: artificial gametes and the embryos produced with them.
AB  - Certain interventions now permit the derivation of mammalian gametes from stem
      cells cultivated from either somatic cells or embryos. These gametes can be used
      in an indefinite cycle of conception in vitro, gamete derivation, conception in
      vitro, and so on, producing genetic generations that live only in vitro. One
      commentator has described this prospect for human beings as eugenics, insofar as
      it would allow for the selection and development of certain traits in human
      beings. This commentary not only offers this topic for discussion, it also wades
      into the ethical fray over the practice. Several possible lines of objection can
      be raised against this practice, but these accounts are by and large insufficient
      as an ethical analysis of this possible, future way of conceiving human children.

PMID- 23966424
TI  - Counselling variation among physicians regarding intestinal transplant for short
      bowel syndrome.
AB  - BACKGROUND: Intestinal transplant in infants with severe short bowel syndrome
      (SBS) is an emerging therapy, yet without sufficient long-term data or
      established guidelines, resulting in possible variation in practice. OBJECTIVES:
      To assess current attitudes and counselling practices among physicians regarding
      intestinal transplant in infants with SBS, and to determine whether counselling
      and management vary between subspecialists or centres. METHODS: A national sample
      of practicing paediatric surgeons and neonatologists was surveyed via the
      American Academy of Paediatrics listserves. Results were analysed by physician
      subspecialty and again by presence or absence of intestinal transplant at
      respondent's centre. RESULTS: The survey was completed by 433 respondents,
      consisting of 363 neonatologists and 70 paediatric surgeons. Fifty-seven
      respondents (13.2%) practiced at a centre that performed intestinal transplants
      in children. The vast majority of respondents (91% for preterm, 95% for term
      neonates) felt that maintaining a neonate with SBS on total parenteral nutrition
      for intestinal transplant was ethically optional (neither impermissible nor
      obligatory), and that parents should be given an informed choice whether to
      pursue that option. However, only 33% indicated they often/always offer
      intestinal transplant as a treatment option to families in this situation.
      CONCLUSIONS: There is a marked disparity between individual physicians' beliefs
      regarding the acceptability of intestinal transplant for severe SBS and their
      reported practice. Wide variability exists among physicians with respect to their
      knowledge, beliefs and practice regarding severe SBS, raising concerns about
      transparency and justice. Survival data prior to transplant, currently
      unavailable, are essential to rational decision making and informed parental
      permission.

PMID- 23966425
TI  - Sodium and potassium intakes among US infants and preschool children, 2003-2010.
AB  - BACKGROUND: Data are limited on usual sodium and potassium intakes relative to
      age-specific recommendations and the sodium:potassium ratio in infants and
      preschoolers, especially among those aged <2 y, who are black or breastfed.
      OBJECTIVE: The usual sodium intake above the Tolerable Upper Intake Levels (ULs),
      potassium intakes above Adequate Intakes (AIs), the sodium:potassium ratio, and
      sodium density (mg/kcal) among US infants and preschoolers by age group, as
      applicable, were estimated and compared by race-ethnicity and current
      breastfeeding status. DESIGN: Data were analyzed among 3 groups of children (aged
      7-11 mo, 1-3 y, and 4-5 y) from the NHANES 2003-2010 by using measurement error
      models. RESULTS: Seventy-nine percent of children aged 1-3 y and 87% of those
      aged 4-5 y exceeded their sodium UL; among non-Hispanic black children, the
      estimates were 84% and 97%, respectively. For potassium, 97% of infants, 5% of
      children aged 1-3 y, and 0.4% aged 4-5 y met their AIs. Compared with non
      Hispanic whites and Mexican Americans, non-Hispanic black infants and
      preschoolers had higher mean sodium density and sodium:potassium ratios.
      Currently breastfed infants and children consumed, on average, less sodium than
      those who were not breastfed (382 +/- 53 compared with 538 +/- 22 mg in those
      aged 7-11 mo and 1154 +/- 88 compared with 1985 +/- 24 mg in those aged 1-3 y,
      respectively), but the sodium:potassium ratio did not differ. CONCLUSIONS: Most
      US preschoolers, particularly non-Hispanic blacks, consume too much sodium, and
      nearly all do not consume enough potassium. Data that suggest that currently
      breastfed infants consume less sodium than do those who are not breastfeeding
      merit further investigation.

PMID- 23966426
TI  - An undigested gliadin peptide activates innate immunity and proliferative
      signaling in enterocytes: the role in celiac disease.
AB  - BACKGROUND: On ingestion of gliadin, the major protein component of wheat and
      other cereals, the celiac intestine is characterized by the proliferation of
      crypt enterocytes with an inversion of the differentiation/proliferation program.
      Gliadins and A-gliadin peptide P31-43, in particular, act as growth factors for
      crypt enterocytes in patients with celiac disease (CD). The effects of gliadin on
      crypt enterocyte proliferation and activation of innate immunity are mediated by
      epidermal growth factors (EGFs) and innate immunity mediators [interleukin 15
      (IL15)]. OBJECTIVE: The aim of this study was to determine the molecular basis of
      proliferation and innate immune response to gliadin peptides in enterocytes.
      DESIGN: The CaCo-2 cell line was used to study EGF-, IL15-, and P31-43-induced
      proliferation. Silencing messenger RNAs and blocking EGF receptor and IL15
      antibodies have been used to study proliferation in CaCo-2 cells and intestinal
      biopsy samples from patients with CD and control subjects. RESULTS: In the CaCo-2
      cell model, IL15 and EGF cooperated to induce proliferation in intestinal
      epithelial cells at both the transcriptional and posttranscriptional levels, and
      the respective receptors interacted to activate each other's signaling. In
      addition, the effects of the P31-43 peptide on CaCo-2 cell proliferation and
      downstream signaling were mediated by cooperation between EGF and IL15. The
      increased crypt enterocyte proliferation in intestinal biopsy samples from
      patients with CD was reduced by EGF receptor and IL15 blocking antibodies only
      when used in combination. CONCLUSIONS: EGF receptor/IL15R-alpha cooperation
      regulates intestinal epithelial cell proliferation induced by EGF, IL15, and the
      gliadin peptide P31-43. Increased proliferation of crypt enterocytes in the
      intestine of CD patients is mediated by EGF/IL15 cooperation.

PMID- 23966427
TI  - Sugar-sweetened beverages and weight gain in children and adults: a systematic
      review and meta-analysis.
AB  - BACKGROUND: The relation between sugar-sweetened beverages (SSBs) and body weight
      remains controversial. OBJECTIVE: We conducted a systematic review and meta
      analysis to summarize the evidence in children and adults. DESIGN: We searched
      PubMed, EMBASE, and Cochrane databases through March 2013 for prospective cohort
      studies and randomized controlled trials (RCTs) that evaluated the SSB-weight
      relation. Separate meta-analyses were conducted in children and adults and for
      cohorts and RCTs by using random- and fixed-effects models. RESULTS: Thirty-two
      original articles were included in our meta-analyses: 20 in children (15 cohort
      studies, n = 25,745; 5 trials, n = 2772) and 12 in adults (7 cohort studies, n =
      174,252; 5 trials, n = 292). In cohort studies, one daily serving increment of
      SSBs was associated with a 0.06 (95% CI: 0.02, 0.10) and 0.05 (95% CI: 0.03,
      0.07)-unit increase in BMI in children and 0.22 kg (95% CI: 0.09, 0.34 kg) and
      0.12 kg (95% CI: 0.10, 0.14 kg) weight gain in adults over 1 y in random- and
      fixed-effects models, respectively. RCTs in children showed reductions in BMI
      gain when SSBs were reduced [random and fixed effects: -0.17 (95% CI: -0.39,
      0.05) and -0.12 (95% CI: -0.22, -0.2)], whereas RCTs in adults showed increases
      in body weight when SSBs were added (random and fixed effects: 0.85 kg; 95% CI:
      0.50, 1.20 kg). Sensitivity analyses of RCTs in children showed more pronounced
      benefits in preventing weight gain in SSB substitution trials (compared with
      school-based educational programs) and among overweight children (compared with
      normal-weight children). CONCLUSION: Our systematic review and meta-analysis of
      prospective cohort studies and RCTs provides evidence that SSB consumption
      promotes weight gain in children and adults.

PMID- 23966429
TI  - Central tenet of cancer cachexia therapy: do patients with advanced cancer have
      exploitable anabolic potential?
AB  - BACKGROUND: Skeletal muscle wasting is considered the central feature of
      cachexia, but the potential for skeletal muscle anabolism in patients with
      advanced cancer is unproven. OBJECTIVE: We investigated the clinical course of
      skeletal muscle wasting in advanced cancer and the window of possible muscle
      anabolism. DESIGN: We conducted a quantitative analysis of computed tomography
      (CT) images for the loss and gain of muscle in population-based cohorts of
      advanced cancer patients (lung, colorectal, and pancreas cancer and
      cholangiocarcinoma) in a longitudinal observational study. RESULTS: Advanced
      cancer patients (n = 368; median survival: 196 d) had a total of 1279 CT images
      over the course of their disease. With consideration of all time points, muscle
      loss occurred in 39% of intervals between any 2 scans. However, the overall
      frequency of muscle gain was 15.4%, and muscle was stable in 45.6% of intervals
      between any 2 scans, which made the maintenance or gain of muscle the predominant
      behavior. Multinomial logistic regression revealed that being within 90 d
      (compared with >90 d) from death was the principal risk factor for muscle loss
      (OR: 2.67; 95% CI: 1.45, 4.94; P = 0.002), and muscle gain was correspondingly
      less likely (OR: 0.37; 95% CI: 0.20, 0.69; P = 0.002) at this time. Sex, age,
      BMI, and tumor group were not significant predictors of muscle loss or gain.
      CONCLUSIONS: A window of anabolic potential exists at defined early phases of the
      disease trajectory (>90 d survival), creating an opportunity for nutritional
      intervention to stop or reverse cachexia. Cancer patients within 90 d of death
      have a low likelihood of anabolic potential.

PMID- 23966428
TI  - Vitamin D intake and lung cancer risk in the Women's Health Initiative.
AB  - BACKGROUND: Prior research suggests that vitamin D protects against lung cancer
      only among certain subgroups. OBJECTIVES: We investigated whether vitamin D
      intake was associated with lung cancer and explored whether vitamin A intake
      modified the association. DESIGN: Prospective cohort data from 128,779
      postmenopausal women, including 1771 incident lung cancers in the Women's Health
      Initiative (Clinical Trials and Observational Study) 1993-2010, were analyzed.
      Twelve percent of women received active intervention (1 g Ca + 400 IU vitamin
      D3/d) in the Calcium/Vitamin D Trial. Baseline total intake included both dietary
      intake (from food-frequency questionnaires) and supplement intake (from bottle
      labels). HRs were estimated by Cox proportional hazard models. RESULTS: No
      significant association was observed overall. Among never smokers, a total
      vitamin D intake >=400 IU/d was significantly associated with lower risks of lung
      cancer (HR: 0.37; 95% CI: 0.18, 0.77 for >=800 compared with <100 IU/d; P-trend =
      0.01). No significant effect modification of total vitamin A intake on the
      association between total vitamin D intake and lung cancer was found. However,
      the Calcium/Vitamin D Trial active intervention was significantly associated with
      a lower lung cancer risk only among women with a vitamin A intake <1000 MUg/d
      retinol activity equivalents (HR: 0.69; 95% CI: 0.50, 0.96; P-interaction =
      0.09). CONCLUSIONS: Vitamin D intake was associated with a lower lung cancer risk
      in never-smoking, postmenopausal women. Lower vitamin A intake may be important
      for a beneficial association of 1 g Ca + 400 IU vitamin D3 supplementation with
      lung cancer. This trial was registered at clinicaltrials.gov as NCT00000611.

PMID- 23966431
TI  - Contribution of fruit and vegetable intake to hydration status in schoolchildren.
AB  - BACKGROUND: The specific effects of fruit and vegetable (F&V) intake on water
      balance and consequently on 24-h hydration status (HS) are unknown. OBJECTIVES:
      In a large observational cohort of German children, we examined whether a higher
      F&V intake per se is associated with improved HS and attempted to quantify the
      influence of greater consumption of F&Vs on HS. DESIGN: A total of 1286 complete
      3-d weighed dietary records and 24-h urine samples for 442 children (4- to 10-y
      olds) collected in 2000-2010 in the Dortmund Nutritional and Anthropometric
      Longitudinally Designed Study were analyzed. Free water reserve [FWR; urine
      volume (mL/24 h) minus obligatory urine volume (mL/24 h)] served as an HS
      biomarker. Median FWR and water balance variables were analyzed in different
      categories of solid-F&V intakes. Repeated-measures regression models (PROC MIXED;
      SAS Institute), adjusted for all other dietary water sources, were used to
      quantify the separate effects of solid-F&V and F&V-juice consumption on FWR.
      RESULTS: Negative FWR values, which indicated risk of hypohydration, were
      observed in 22% of children. FWR was significantly higher in solid-F&V consumers
      with high intakes than in those with low intakes (P < 0.0001). PROC MIXED models
      predicted an increase of 46 mL in FWR (average in boys and girls) when increasing
      solid-F&V intake by 100 g. Similar results were observed for F&V juice (beta =
      43, P < 0.0001). Drinking water and milk were the other significant dietary
      predictors of FWR. Solid F&Vs and F&V juices contributed 12% and 10%,
      respectively, to total water intake. CONCLUSIONS: These data confirm that regular
      intake of F&Vs may relevantly improve HS in children. Dietary interventions to
      increase F&V intake may be a promising strategy to achieve positive water balance
      in this population.

PMID- 23966430
TI  - Breastfeeding and ovarian cancer risk: a meta-analysis of epidemiologic studies.
AB  - BACKGROUND: Epidemiologic studies have yielded inconsistent findings between
      breastfeeding and epithelial ovarian cancer (EOC) risk. OBJECTIVE: We performed a
      meta-analysis to summarize available evidence of the association between
      breastfeeding and breastfeeding duration and EOC risk from published cohort and
      case-control studies. DESIGN: Relevant published studies were identified by a
      search of MEDLINE through December 2012. Two authors (T-TG and Q-JW)
      independently performed the eligibility evaluation and data abstraction. Study
      specific RRs from individual studies were pooled by using a random-effects model,
      and heterogeneity and publication-bias analyses were conducted. RESULTS: Five
      prospective and 30 case-control studies were included in this analysis. The
      pooled RR for ever compared with never breastfeeding was 0.76 (95% CI: 0.69,
      0.83), with moderate heterogeneity (Q = 69.4, P < 0.001, I(2) = 55.3%). Risk of
      EOC decreased by 8% for every 5-mo increase in the duration of breastfeeding (RR:
      0.92; 95% CI: 0.90, 0.95). The risk reduction was similar for borderline and
      invasive EOC and was consistent within case-control and cohort studies.
      CONCLUSIONS: Results of this meta-analysis support the hypothesis that ever
      breastfeeding and a longer duration of breastfeeding are associated with lower
      risks of EOC. Additional research is warranted to focus on the association with
      cancer grade and histologic subtypes of EOC.

PMID- 23966432
TI  - In this issue of Occupational Medicine.

PMID- 23966433
TI  - The heartsink consultation in occupational health practice.

PMID- 23966434
TI  - The silent killer.

PMID- 23966435
TI  - Clare Leighton, Farming, Wedgwood plate 1952.

PMID- 23966436
TI  - Occupational management of type I latex allergy.
AB  - BACKGROUND: Although the incidence of type 1 latex allergy has decreased in
      recent years with the introduction of powder-free low-protein (PFLP) latex
      gloves, type 1 latex allergy is still commonly found among workers who use
      natural rubber latex (NRL) gloves at work. AIMS: To elucidate the optimal
      management of workers with type 1 latex allergy whose work necessitates the use
      of NRL gloves in the workplace. METHODS: A sensitive electronic search of
      relevant bibliographic databases was performed with related search terms for
      articles from 1 January 1990 to 1 September 2010. Relevant abstracts were
      reviewed, and studies that furnished data on the management of type 1 latex
      allergy in the workplace were extracted. Articles for inclusion in the review
      were appraised using the Scottish Intercollegiate Guideline Network methodology.
      RESULTS: A total of 7041 abstracts were retrieved; 12 articles met the inclusion
      criteria for the review. We found moderately strong and consistent evidence that
      avoidance of NRL in the workplace reduces both symptoms and markers of
      sensitization in latex-allergic individuals. There is limited evidence that latex
      allergic workers can continue to use PFLP gloves with no worsening of symptoms,
      provided that their co-workers also use PFLP latex or non-latex gloves.
      CONCLUSIONS: Individuals with type 1 latex allergy whose work necessitates them
      wearing latex gloves may continue in their job provided that adjustments are made
      to ensure that they are not exposed to powdered latex gloves.

PMID- 23966438
TI  - Managers' perception of mental health diagnosis in doctors.

PMID- 23966439
TI  - Professor Geoffrey Warren Hanks (1946-2013): an appreciation of his contribution
      to Palliative Medicine.

PMID- 23966440
TI  - Parental challenges when children are diagnosed with life-limiting illnesses in a
      context of poverty.

PMID- 23966444
TI  - Association of interankle systolic blood pressure difference with peripheral
      vascular disease and left ventricular mass index.
AB  - BACKGROUND: An interankle systolic blood pressure (SBP) difference has been
      associated with overall and cardiovascular mortality. We investigated whether an
      association existed between this difference and ankle-brachial index (ABI),
      brachial-ankle pulse wave velocity (baPWV), and echocardiographic parameters.
      METHODS: A total of 1,059 patients referred for echocardiographic examination
      were included in the study. The 4 limb blood pressures were measured
      simultaneously using an ABI-form device. RESULTS: We performed multivariate
      forward analysis to determine the factors associated with an interankle SBP
      difference >= 15mm Hg. An ABI < 0.9 (P < 0.001), high baPWV (P < 0.001), and
      increased left ventricular mass index (LVMI; P = 0.004) were associated with an
      interankle SBP difference >= 15mm Hg. Also, the addition of an interankle SBP
      difference >= 15mm Hg to a model of clinical features could significantly improve
      the value in predicting ABI < 0.9 (P < 0.001) and increased LVMI (P = 0.036).
      CONCLUSIONS: Our study demonstrated that ABI < 0.9, high baPWV, and increased
      LVMI were independently associated with an interankle SBP difference >= 15mm Hg.
      Also, an interankle SBP difference >= 15mm Hg could offer an extra benefit in
      identifying patients with ABI < 0.9 and increased LVMI beyond conventional
      clinical features. Hence, calculation of interankle SBP difference may provide
      additional information for identifying patients with peripheral vascular disease
      and increased LVMI.

PMID- 23966445
TI  - The tale of hearts and reason: the influence of mood on decision making.
AB  - In decision-making research, one important aspect of real-life decisions has so
      far been neglected: the mood of the decision maker when generating options. The
      authors tested the use of the take-the-first (TTF) heuristic and extended the TTF
      model to understand how mood influences the option-generation process of
      individuals in two studies, the first using a between-subjects design (30
      nonexperts, 30 near-experts, and 30 experts) and the second conceptually
      replicating the first using a within-subject design (30 nonexperts). Participants
      took part in an experimental option-generation task, with 31 three-dimensional
      videos of choices in team handball. Three moods were elicited: positive, neutral,
      and negative. The findings (a) replicate previous results concerning TTF and (b)
      show that the option-generation process was associated with the physiological
      component of mood, supporting the neurovisceral integration model. The extension
      of TTF to processing emotional factors is an important step forward in explaining
      fast choices in real-life situations. 

PMID- 23966446
TI  - Executive function during acute exercise: the role of exercise intensity.
AB  - This study was designed to examine the modulation of executive functions during
      acute exercise and to determine whether exercise intensity moderates this
      relationship. Eighty college-aged adults were recruited and randomly assigned
      into one of the four following groups: control, 30%, 50%, and 80% heart rate
      reserve. The Wisconsin Card Sorting Test (WCST) was administered during each
      intervention. The results indicated that the majority of the WCST performances
      were impaired in the high exercise intensity group relative to those of the other
      three groups, whereas similar performance rates were maintained in the low- and
      moderate-intensity groups. These findings suggest that transient hypofrontality
      occurs during high-intensity exercise, but not during low- and moderate-intensity
      exercises. Future research aimed at employing the dual-mode theory, and applying
      the reticular-activating hypofrontality model is recommended to further the
      current knowledge. 

PMID- 23966447
TI  - Interactions between performance pressure, performance streaks, and attentional
      focus.
AB  - How is performance under pressure influenced by the history of events that
      precede it, and how does the pressure outcome influence the series of events that
      follow? A baseball batting simulation was used with college players to
      investigate these questions. In Experiment 1, the difficulty of the simulation
      was first adaptively adjusted to equate performance level. Batters next completed
      20 at-bats used to classify them into one of three performance groups (normal,
      cold streak, or hot streak) followed by a one at-bat pressure condition. Finally,
      performance was evaluated over a period of 20 postpressure at-bats. In Experiment
      2, a series of secondary tasks were added to assess attentional focus. In both
      experiments, whether batters succeeded or failed under pressure was significantly
      related to their performance history immediately before the pressure event, with
      the normal group having the poorest pressure performance. Performance
      postpressure was significantly related to both the pressure outcome and
      prepressure performance. These performance effects were related to changes in the
      batter's attentional focus as shown by changes in secondary task accuracy. 

PMID- 23966448
TI  - Who thrives under pressure? Predicting the performance of elite academy
      cricketers using the cardiovascular indicators of challenge and threat states.
AB  - This study assessed whether cardiovascular (CV) reactivity patterns indexing
      challenge and threat states predicted batting performance in elite male county (N
      = 12) and national (N = 30) academy cricketers. Participants completed a batting
      test under pressure, before which CV reactivity was recorded in response to ego
      threatening audio instructions. Self-reported self-efficacy, control, achievement
      goals, and emotions were also assessed. Challenge CV reactivity predicted
      superior performance in the Batting Test, compared with threat CV reactivity. The
      relationships between self-report measures and CV reactivity, and self-report
      measures and performance were inconsistent. A small subsample of participants who
      exhibited threat CV reactivity, but performed well, reported greater self
      efficacy than participants who exhibited threat CV reactivity, but performed
      poorly. Also a small subsample of participants who exhibited challenge
      reactivity, but performed poorly, had higher avoidance goals than participants
      with challenge reactivity who performed well. The mechanisms for the observed
      relationship between CV reactivity and performance are discussed alongside
      implications for future research and applied practice. 

PMID- 23966449
TI  - Physical activity and trial-by-trial adjustments of response conflict.
AB  - The relationship of physical activity to trial-by-trial adjustments of response
      conflict was assessed using behavioral task performance, the N2 event-related
      brain potential component, and phase-locking values (PLVs) in a lower gamma band
      during a perceptual conflict task. Nineteen physically active and 19 inactive
      young adults (mean age = 21.3 years) performed a Navon task, using a global
      letter made up of local letters of either the same kind (congruent trials) or a
      different kind (incongruent trials). Findings revealed that active individuals
      exhibited smaller N2 amplitudes and greater PLVs on incongruent trials that were
      preceded by incongruent trials compared with those preceded by congruent trials.
      Such phenomena were not observed for inactive individuals. These results suggest
      that greater physical activity is associated with larger trial-by-trial
      adjustments of response conflict, which we attribute to upregulation of top-down
      cognitive control and reductions in response conflict. 

PMID- 23966451
TI  - Psychological mechanisms underlying doping attitudes in sport: motivation and
      moral disengagement.
AB  - We examined whether constructs outlined in self-determination theory (Deci &
      Ryan, 2002), namely, autonomy-supportive and controlling motivational climates
      and autonomous and controlled motivation, were related to attitudes toward
      performance-enhancing drugs (PEDs) in sport and drug-taking susceptibility. We
      also investigated moral disengagement as a potential mediator. We surveyed a
      sample of 224 competitive athletes (59% female; M age = 20.3 years; M = 10.2
      years of experience participating in their sport), including 81 elite athletes.
      Using structural equation modeling analyses, our hypothesis proposing positive
      relationships with controlling climates, controlled motivation, and PEDs
      attitudes and susceptibility was largely supported, whereas our hypothesis
      proposing negative relationships among autonomous climate, autonomous motivation,
      and PEDs attitudes and susceptibility was not supported. Moral disengagement was
      a strong predictor of positive attitudes toward PEDs, which, in turn, was a
      strong predictor of PEDs susceptibility. These findings are discussed from both
      motivational and moral disengagement viewpoints. 

PMID- 23966450
TI  - Coping under pressure: employing emotion regulation strategies to enhance
      performance under pressure.
AB  - Performing under high pressure is an emotional experience. Hence, the use of
      emotion regulation strategies may prove to be highly effective in preventing
      choking under pressure. Using a golf putting task, we investigated the role of
      arousal on declined sport performance under pressure (pilot study) and the
      effectiveness of emotion regulation strategies in alleviating choking under
      pressure (main study). The pilot study showed that pressure resulted in decreased
      performance and this effect was partially mediated by increased arousal. The main
      study, a field study, showed that whereas the choking effect was observed in the
      control condition, reappraisal and, particularly, distraction were effective
      emotion regulation strategies in helping people to cope instead of choke under
      pressure. These findings suggest that interventions that aim to prevent choking
      under pressure could benefit from including emotion regulation strategies. 

PMID- 23966452
TI  - Acute exercise enhances preschoolers' ability to sustain attention.
AB  - A growing body of research has illuminated beneficial effects of a single bout of
      physical activity (i.e., acute exercise) on cognitive function in school-age
      children. However, the influence of acute exercise on preschoolers' cognitive
      function has not been reported. To address this shortcoming, the current study
      examined the effects of a 30-min bout of exercise on preschoolers' cognitive
      function. Preschoolers' cognitive function was assessed following a single bout
      of exercise and a single sedentary period. Results revealed that, after engaging
      in a bout of exercise, preschoolers exhibited markedly better ability to sustain
      attention, relative to after being sedentary (p = .006, partial eta square =
      .400). Based on these findings, providing exercise opportunities appears to
      enhance preschoolers' cognitive function. 

PMID- 23966453
TI  - Modification of erythrocyte membrane proteins, enzymes and transport mechanisms
      in chronic alcoholics: an in vivo and in vitro study.
AB  - AIM: The aim of the study was to elucidate the molecular mechanisms underlying
      the alcohol perturbation leading to deleterious effects on erythrocyte membrane
      transport in chronic alcoholics. METHODS: Membrane bound enzyme activities such
      as Na(+), K(+)-ATPase, Ca(2+),Mg(2+)-ATPase and acetylcholine esterase and
      membrane transport analysis by in vitro and erythrocyte membrane profile analysis
      in controls and chronic alcoholic red cells were analyzed. RESULTS: It was
      observed that decreased Na(+), K(+)-ATPase enzyme activity and increased
      activities of Ca(2+),Mg(2+)-ATPase and acetylcholine esterase in chronic
      alcoholics compared to controls. The in vitro studies of erythrocytes suggested
      that there is an increased uptake of glucose through chronic alcoholic red cells.
      However, glucose utilization by chronic alcoholic red cells was decreased. An
      increased sensitivity of ouabain for its binding site on Na(+), K(+)-ATPase in
      chronic alcoholic erythrocyte membrane was evident from this study. Though there
      appears to be an increased Na(+) influx in chronic alcoholic cells, the status of
      Na(+) transport is not altered much. However, ouabain caused slight disturbances
      in the transport of sodium, similar disturbances in the potassium transport
      resulting in much accumulation of potassium in red cells. CONCLUSIONS: It was
      concluded that chronic alcohol consumption modified certain membrane bound
      proteins, enzymes and transport mechanisms in chronic alcoholics.

PMID- 23966454
TI  - Tuberculous meningitis.

PMID- 23966455
TI  - EBV-driven diffuse large B-cell lymphoma confined to the liver in a patient with
      a history of idiopathic CD4 lymphocytopenia.
AB  - Idiopathic CD4 lymphocytopenia (ICL) is a rare immunodeficiency disorder. We
      describe a 49-year-old woman with a history of ICL who developed hepatic Epstein
      Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL). ICL was
      diagnosed at a time of her presentation with varicella-zoster virus (VZV)
      meningoencephalitis and chorioretinitis. Her CD4 count subsequently improved but
      remained at the lower limits of the normal range. Five years later she presented
      with cough, fever and night-sweat. She was found to have multiple liver nodules
      on MRI, fluorodeoxyglucose (FDG) avid on the positron emission tomography (PET)
      CT, histologically defined as DLBCL, EBV positive and of non-germinal centre
      type. To our knowledge this is the first reported case of EBV-positive DLBCL
      localised to the liver in the context of ICL. EBV-positive DLBCL typically occurs
      in immunocompromised individuals. The corticosteroid therapy she received for VZV
      meningoencephalitis may have contributed to the EBV reactivation with subsequent
      EBV-driven malignant transformation of B-cells. 

PMID- 23966456
TI  - Isolated cerebellar tuberculoma mimicking posterior cranial fossa tumour.
AB  - Isolated central nervous system (CNS) tuberculoma is a rare disease. This disease
      is associated with high morbidity and mortality, despite modern methods of
      detection and treatment. CNS tuberculosis can present as meningitis,
      arachnoiditis, tuberculomas or the uncommon form of tuberculous subdural empyema
      and brain abscess. We present the clinical, radiological and pathological
      findings of cerebellar tuberculoma in an Iranian immunocompetent patient
      mimicking a malignant tumour. 

PMID- 23966457
TI  - Massive per rectal bleeding in a child due to caecal arteriovenous malformation
      treated successfully by embolisation.
AB  - A 12-year-old girl presented with a sudden onset of per rectal bleeding. After
      admission, she had further episodes of large volume per rectal bleeding and
      developed hypotensive shock. Hence a massive haemorrhage protocol was activated.
      Surgical, paediatric and anaesthetic support was sought immediately. Further
      resuscitation with packed red cells, platelets and fresh frozen plasma was
      successful. An urgent CT angiogram of the abdomen confirmed active arterial
      bleeding from an arteriovenous malformation in the caecum. After a detailed
      discussion between the surgeons and the interventional radiologists, it was
      decided to attempt therapeutic embolisation first, failing which surgery was the
      option. The patient and family were fully informed. Through a right femoral
      approach under local anaesthesia, the superior mesenteric artery was catheterised
      and the bleeding vessel was successfully controlled with two microembolisation
      coils. Except for some initial abdominal discomfort, she made an uneventful
      recovery and was discharged home. 

PMID- 23966458
TI  - Low complement levels in paediatric systemic lupus erythematosus and the risk of
      bacteraemia.
AB  - This report describes an 11-year-old girl with systemic lupus erythematosus (SLE)
      with long-standing low levels of complement proteins. A disease period with lupus
      nephritis (class IIIa) was complicated by Staphylococcus aureus bacteraemia and
      osteomyelitis. She was treated with high-dose immunosuppressants and 6 weeks of
      high-dose intravenous antibiotics. The clinician should be aware of bacteraemia
      in SLE with secondary complement deficiency. 

PMID- 23966459
TI  - Isolated sacral dislocation in a 4-year-old child.
AB  - Sacral dislocation is an uncommon form of injury in childhood. A 4-year-old girl
      who was injured in a motor vehicle accident was seen in the emergency room. On
      physical examination, ecchymosis and tenderness in the abdomen and sacral region
      was identified. Radiographs revealed no pelvic pathology. CT was performed owing
      to the patient's sacral and abdominal tenderness. Dislocations were identified at
      the sacral third and fourth vertebrae without any fractures. The patient was
      discharged 10 days later with a recommendation for 6 weeks bed rest and an
      appointment for an outpatient follow-up examination. At the post-traumatic second
      month examination, the patient was walking normally. In the radiograph and MRI
      that were taken a year later, the dislocation was observed to have fused
      completely, and no pressure was seen on any anatomical structure. No functional
      pathology was identified during the interview with the family. 

PMID- 23966460
TI  - Difficulty in the intravesical morcellation procedure for leiomyoma of the
      prostate enucleated by HoLEP.
AB  - Leiomyoma of prostate are rare benign neoplasms that are usually diagnosed
      incidentally through postoperative pathological examination. A 70-year-old man is
      presented with severe symptoms of lower urinary tract obstruction. Although a
      digital rectal examination and the prostate-specific antigen level did not
      suggest malignancy, transrectal ultrasonography showed an unusual homogenous
      echoic mass measuring 45*37 mm in size in the prostate. A needle biopsy was
      performed and pathological diagnosis was prostatic leiomyoma. Holmium laser
      enucleation of prostate (HoLEP) was chosen and performed to resect the tumour.
      Although the enucleation step presented no problems, the morcellation procedure
      using a conventional transurethral mechanical morcellator was very difficult
      owing to the firmness of the tissue. By using a bipolar erectrosurgical loop,
      fragmentation and removal of tissue was accomplished. This is the first case
      reported of these rare neoplasms in which HoLEP was offered as a less invasive
      surgical approach. We emphasise the firmness of the leiomyomatous tissue, which
      would lead to morcellation failure. 

PMID- 23966461
TI  - Spinal cord schistosomiasis presenting as a spinal cord syndrome.

PMID- 23966462
TI  - Hashimoto's thyroiditis: an accidental discovery of a lingual thyroid in a 7-year
      old child.
AB  - An ectopic thyroid located at the base of the tongue is a rare entity, resulting
      from early developmental defects of thyroid gland embryogenesis during its
      descent from the foramen caecum to its normal eutopic pretracheal site. This
      condition is the main cause of congenital primary hypothyroidism, even though
      signs and symptoms of thyroid dysfunction may also appear later in childhood.
      Lingual thyroid may sometimes present with symptoms of respiratory obstruction or
      feeding difficulties. We illustrate the case of a 7-year-old girl with
      subclinical hypothyroidism due to Hashimoto's thyroiditis arising in a lingual
      thyroid. She had never suffered from upper airway obstructive symptoms, but did
      refer a 3-month history of cough. Rapid normalisation of thyroid-stimulating
      hormone levels and termination of the cough were attained when the L-thyroxine
      treatment started. After 6 months a significant reduction of lingual thyroid size
      was also noted. The diagnostic procedures and therapeutic options in childhood
      are discussed. 

PMID- 23966463
TI  - Torted gallbladder causing massive distension and gross necrosis; a rare surgical
      emergency.
AB  - Gallbladder torsion is rare and is more frequently seen in elderly women.
      Published case reports comment that diagnosis of this entity can be made
      preoperatively through imaging with some advocating removal laparoscopically.
      This case reports an elderly woman who underwent emergency laparotomy for a
      massively distended gallbladder with suspected cholecystitis. At laparotomy the
      gallbladder was found to be torted over 360 degrees  round its pedicle of the
      cystic duct and artery. The torsion was so pronounced that the gallbladder was
      massively distended and grossly necrotic with a high risk of perforation. As the
      pedicle was long the gallbladder was easily separated form the liver and removed
      in its entirety. This case presented significant diagnostic and management
      difficulties. By observing the clinical features in the triad of triads for
      gallbladder volvulus prompt diagnosis, investigation and treatment can be started
      for this rare emergency presentation. 

PMID- 23966464
TI  - Acute thyroid swelling and elevated C reactive protein.
AB  - A 34-year-old lady presented with a painful swelling of the left thyroid lobe
      since 1 week and elevated C reactive protein (CRP) above 100 mg/L. An ultrasound
      examination revealed a thyroid cyst with partly solid component, suitable with a
      haemorrhage into a cyst. The serum thyroid stimulating hormone (TSH), as well as
      peripheral thyroid hormones, was in the normal range. The acute swelling could be
      well explained by a haemorrhage, but not an elevated CRP. Her medical history was
      uneventful apart from a tooth extraction 2 weeks ago due to an infection.
      Therefore, our hypothesis was a haemorrhage into a pre-existing thyroid cyst
      during bacteraemia caused by the tooth infection. Conservative treatment with the
      aim of delayed hemithyreoidectomy failed due to a second episode of haemorrhage.
      During surgical resection pus drained out of the cyst and the histological report
      afterwards confirmed our tentative diagnosis. The patient was discharged 2 days
      later. 

PMID- 23966465
TI  - Protein kinase C activation decreases peripheral actin network density and
      increases central nonmuscle myosin II contractility in neuronal growth cones.
AB  - Protein kinase C (PKC) can dramatically alter cell structure and motility via
      effects on actin filament networks. In neurons, PKC activation has been
      implicated in repulsive guidance responses and inhibition of axon regeneration;
      however, the cytoskeletal mechanisms underlying these effects are not well
      understood. Here we investigate the acute effects of PKC activation on actin
      network structure and dynamics in large Aplysia neuronal growth cones. We provide
      evidence of a novel two-tiered mechanism of PKC action: 1) PKC activity enhances
      myosin II regulatory light chain phosphorylation and C-kinase-potentiated protein
      phosphatase inhibitor phosphorylation. These effects are correlated with
      increased contractility in the central cytoplasmic domain. 2) PKC activation
      results in significant reduction of P-domain actin network density accompanied by
      Arp2/3 complex delocalization from the leading edge and increased rates of
      retrograde actin network flow. Our results show that PKC activation strongly
      affects both actin polymerization and myosin II contractility. This synergistic
      mode of action is relevant to understanding the pleiotropic reported effects of
      PKC on neuronal growth and regeneration. 

PMID- 23966466
TI  - Insulin responsiveness of glucose transporter 4 in 3T3-L1 cells depends on the
      presence of sortilin.
AB  - Insulin-dependent translocation of glucose transporter 4 (Glut4) to the plasma
      membrane of fat and skeletal muscle cells plays the key role in postprandial
      clearance of blood glucose. Glut4 represents the major cell-specific component of
      the insulin-responsive vesicles (IRVs). It is not clear, however, whether the
      presence of Glut4 in the IRVs is essential for their ability to respond to
      insulin stimulation. We prepared two lines of 3T3-L1 cells with low and high
      expression of myc7-Glut4 and studied its translocation to the plasma membrane
      upon insulin stimulation, using fluorescence-assisted cell sorting and cell
      surface biotinylation. In undifferentiated 3T3-L1 preadipocytes, translocation of
      myc7-Glut4 was low regardless of its expression levels. Coexpression of sortilin
      increased targeting of myc7-Glut4 to the IRVs, and its insulin responsiveness
      rose to the maximal levels observed in fully differentiated adipocytes. Sortilin
      ectopically expressed in undifferentiated cells was translocated to the plasma
      membrane regardless of the presence or absence of myc7-Glut4. AS160/TBC1D4 is
      expressed at low levels in preadipocytes but is induced in differentiation and
      provides an additional mechanism for the intracellular retention and insulin
      stimulated release of Glut4. 

PMID- 23966467
TI  - Distinct roles for antiparallel microtubule pairing and overlap during early
      spindle assembly.
AB  - During spindle assembly, microtubules may attach to kinetochores or pair to form
      antiparallel pairs or interpolar microtubules, which span the two spindle poles
      and contribute to mitotic pole separation and chromosome segregation. Events in
      the specification of the interpolar microtubules are poorly understood. Using
      three-dimensional electron tomography and analysis of spindle dynamical behavior
      in living cells, we investigated the process of spindle assembly. Unexpectedly,
      we found that the phosphorylation state of an evolutionarily conserved Cdk1 site
      (S360) in gamma-tubulin is correlated with the number and organization of
      interpolar microtubules. Mimicking S360 phosphorylation (S360D) results in
      bipolar spindles with a normal number of microtubules but lacking interpolar
      microtubules. Inhibiting S360 phosphorylation (S360A) results in spindles with
      interpolar microtubules and high-angle, antiparallel microtubule pairs. The
      latter are also detected in wild-type spindles <1 MUm in length, suggesting that
      high-angle microtubule pairing represents an intermediate step in interpolar
      microtubule formation. Correlation of spindle architecture with dynamical
      behavior suggests that microtubule pairing is sufficient to separate the spindle
      poles, whereas interpolar microtubules maintain the velocity of pole displacement
      during early spindle assembly. Our findings suggest that the number of interpolar
      microtubules formed during spindle assembly is controlled in part through
      activities at the spindle poles. 

PMID- 23966469
TI  - Glycosylation-independent ERAD pathway serves as a backup system under ER stress.
AB  - During endoplasmic reticulum (ER)-associated degradation (ERAD), terminally
      misfolded proteins are retrotranslocated from the ER to the cytosol and degraded
      by the ubiquitin-proteasome system. Misfolded glycoproteins are recognized by
      calnexin and transferred to EDEM1, followed by the ER disulfide reductase ERdj5
      and the BiP complex. The mechanisms involved in ERAD of nonglycoproteins,
      however, are poorly understood. Here we show that nonglycoprotein substrates are
      captured by BiP and then transferred to ERdj5 without going through the
      calnexin/EDEM1 pathway; after cleavage of disulfide bonds by ERdj5, the
      nonglycoproteins are transferred to the ERAD scaffold protein SEL1L by the aid of
      BiP for dislocation into the cytosol. When glucose trimming of the N-glycan
      groups of the substrates is inhibited, glycoproteins are also targeted to the
      nonglycoprotein ERAD pathway. These results indicate that two distinct pathways
      for ERAD of glycoproteins and nonglycoproteins exist in mammalian cells, and
      these pathways are interchangeable under ER stress conditions. 

PMID- 23966471
TI  - Update on manging neuropathic pain.
AB  - Severe chronic neuropathic pain, which can profoundly and negatively affect
      quality of life, is usually caused by damage to peripheral nerve tissue from
      various physical, thermal, or chemical agents and is difficult to relieve.
      Commonly used opioids are quite effective in relieving nociceptive pain, but
      nerves that are damaged send pain-sensing fibers into an area of the spinal cord
      in which there are no mu or kappa receptors to receive opioids or the endogenous
      endorphins that relieve pain. Clinicians who treat neuropathic pain face daunting
      therapeutic challenges, but specific analgesic agents have proven effective in
      relieving that excruciating discomfort. In this article, drugs that target
      neuropathic pain are discussed, and case reports of patients who have overcome
      nerve-related pain are presented. Formulations for effective analgesic
      preparations useful in treating neuropathic pain are included. 

PMID- 23966472
TI  - Elegant compounded solutions for the treatment of thrombosed external
      hemorrhoids.
AB  - A thrombosed external hemorrhoid is a complication of external hemorrhoids.
      Usually, this disease is accompanied by severe pain that lasts for several days.
      The common conservative treatment is a slow, ineffective pain reliever. Surgery
      produces a lot of discomfort and inconvenience, affects the patient's quality of
      life, and presents some risks of post-operative complications. The purpose of
      this article is to propose an elegant compounded preparation to quickly treat the
      pain associated with thrombosed external hemorrhoids with a minimum of side
      effects and complications. 

PMID- 23966470
TI  - Tissue-specific and SRSF1-dependent splicing of fibronectin, a matrix protein
      that controls host cell invasion.
AB  - Cell invasion targets specific tissues in physiological placental implantation
      and pathological metastasis, which raises questions about how this process is
      controlled. We compare dermis and endometrium capacities to support trophoblast
      invasion, using matching sets of human primary fibroblasts in a coculture assay
      with human placental explants. Substituting endometrium, the natural trophoblast
      target, with dermis dramatically reduces trophoblast interstitial invasion. Our
      data reveal that endometrium expresses a higher rate of the fibronectin (FN)
      extra type III domain A+ (EDA+) splicing isoform, which displays stronger matrix
      incorporation capacity. We demonstrate that the high FN content of the
      endometrium matrix, and not specifically the EDA domain, supports trophoblast
      invasion by showing that forced incorporation of plasma FN (EDA-) promotes
      efficient trophoblast invasion. We further show that the serine/arginine-rich
      protein serine/arginine-rich splicing factor 1 (SRSF1) is more highly expressed
      in endometrium and, using RNA interference, that it is involved in the higher EDA
      exon inclusion rate in endometrium. Our data therefore show a mechanism by which
      tissues can be distinguished, for their capacity to support invasion, by their
      different rates of EDA inclusion, linked to their SRSF1 protein levels. In the
      broader context of cancer pathology, the results suggest that SRSF1 might play a
      central role not only in the tumor cells, but also in the surrounding stroma. 

PMID- 23966473
TI  - Missives from Iraq: compounding in the theatre of war-phenytoin solution heals
      severe refractory wounds: an anecdotal report.
AB  - Injuries sustained in an active war zone present some of the greatest therapeutic
      challenges to physicians, healthcare specialists, and patients. The increasing
      sophistication of weapons and the availability of armaments have improved the
      ability of combatants to inflict devastating multisystem wounds, and field
      conditions often compromise the treatment of those who survive their inital
      trauma. Countering these factors are advances in trauma care, which effectively
      treat injuries that once proved quickly fatal. As a result, many victims of war
      are now more likely than ever to require long-term care. 

PMID- 23966468
TI  - Cooperation between Rho-GEF Gef2 and its binding partner Nod1 in the regulation
      of fission yeast cytokinesis.
AB  - Cytokinesis is the last step of the cell-division cycle, which requires precise
      spatial and temporal regulation to ensure genetic stability. Rho guanine
      nucleotide exchange factors (Rho GEFs) and Rho GTPases are among the key
      regulators of cytokinesis. We previously found that putative Rho-GEF Gef2
      coordinates with Polo kinase Plo1 to control the medial cortical localization of
      anillin-like protein Mid1 in fission yeast. Here we show that an adaptor protein,
      Nod1, colocalizes with Gef2 in the contractile ring and its precursor cortical
      nodes. Like gef2, nod1 has strong genetic interactions with various cytokinesis
      mutants involved in division-site positioning, suggesting a role of Nod1 in early
      cytokinesis. We find that Nod1 and Gef2 interact through the C-termini, which is
      important for their localization. The contractile-ring localization of Nod1 and
      Gef2 also depends on the interaction between Nod1 and the F-BAR protein Cdc15,
      where the Nod1/Gef2 complex plays a role in contractile-ring maintenance and
      affects the septation initiation network. Moreover, Gef2 binds to purified
      GTPases Rho1, Rho4, and Rho5 in vitro. Taken together, our data indicate that
      Nod1 and Gef2 function cooperatively in a protein complex to regulate fission
      yeast cytokinesis. 

PMID- 23966474
TI  - Case report: lidocaine mucoadhesive buccal tablets for local relief of mouth
      ulcers.
AB  - A lidocaine-releasing adhesive buccal tablet preparation was developed to treat
      mouth ulcers in a patient who did not tolerate magic mouthwash. The tablet,
      applied locally, was compressed in a manual pellet press from a powder mixture of
      lidocaine hydrochloride, Carbopol-934, sodium carboxymethylcellulose,
      polyvinylpyrrolidone K-30, and D-mannitol. With careful local administration of
      lidocaine from the buccal patch, several side effects of magic mouthwash can be
      avoided. 

PMID- 23966475
TI  - Safe use of topical local anesthetic medications for pain management.

PMID- 23966476
TI  - Promethazine 25 mg/mL in Pluronic Lecithin Organogel for Nausea and Vomiting in a
      Pediatric Patient: A Case Report.
AB  - Nausea and vomiting, especially in pediatric patients, can cause dehydration, the
      treatment for which may require hospitalization . In patients who resist rectal
      dosage forms or are unable to tolerate oral medications, a compounded transdermal
      gel containing an antiemetic agent such as promethazine can provide effective
      relief without producing major adverse effects. In this case report, the
      treatment of severe nausea and vomiting caused by acute viral gastritis in a
      pediatric patient is described, and a formulation for an effective transdermal
      compound is provided. 

PMID- 23966477
TI  - Compounded medications in a hospital setting: patient counseling and staff
      education.
AB  - Patient counseling can be a challenge in a hospital facility, particularly for
      the compounding pharmacist. Since most patient education is provided by nurses
      and physicians, pharmacists must be diligent in educating the hospital staff
      about medications so that the patient or cargiver receives adequate counseling to
      improve compliance with the pharmaceutical care plan, to play an active role in
      monitoring for progress or adverse effects, and to prevent hospital readmission.
      this article discusses the guidelines and standards that have been established by
      the American society of Health-System Pharmacists, the Joint Commission on
      Accreditation of Healthcare Organizations, and the United States Pharmacopeial
      Convention, Inc. in the areas of patient consultation and staff education. 

PMID- 23966478
TI  - Quality-Control Analytical Methods: Pharmaceutical and Analytical Considerations
      of the Significance of pH.
AB  - Most drugs are weak acids or weak bases. The solubility, stability, activity,
      absorption, and bioavailability of these drug molecules are highly pH dependent.
      This article discusses the importance of pH in pharmacuetical preparation and
      analysis. 

PMID- 23966479
TI  - Basics of compounding; considerations for implementing United States pharmacopeia
      chapter 797 pharmaceutical compounding-sterile preparations, part 13.
AB  - A compounding facility, including the staff, bears the responsibility of ensuring
      that any potential soucre of contamination has been considered, properly
      addressed, and documented. Therefore, the design of the compounding facility must
      consider the (1)potential for airborne contamination, (2)work flow,
      (3)efficiency, and (4)personnel comfort. The understanding of a critical site,
      which is any location that is exposed and can allow intrusion of microorganisms
      and/or foreign matter, and the nature of the critical site and exposure is
      paramount in the compounding of sterile preparations. This means that not only
      the design of the facility must be considered but standard operating procedures
      must be in place for personnel, and those procedures must be strictly adhered to.
      This article emphasizes the improtance of considering the critical site during
      compounding procedures, the design and rationale supporting the facility, and
      operational activities surrounding active compounding. 

PMID- 23966480
TI  - Chemical stability of extemporaneously compounded omeprazole formulations: a
      comparison of two methods of compounding.
AB  - Liquid preparations of omeprazole are compounded extemporaneously for patients
      who cannot tolerate or have difficulty with tablets or capsules, such as those
      with a nasogastric tube or jejunal or feeding tube, those with a swallowing
      disorder, and young children and the elderly. Recommendations for preparation of
      a liquid from the enteric-coated pellets of omeprazole capsules are available in
      the literature. The pellets are dissolved in a sodium bicarbonate solution;
      shaking is recommended to aid dissolution. Apparently some pharmacists crush the
      pellets to speed up the compounding process. The aim of this study was to
      investigate the chemical stability of omeprazole in extemporaneously compounded
      liquids prepared by the grinding and shaking methods. A high-performance liquid
      chromatographic method was developed for evaluation of chemical stability.
      Samples were stored at 2 deg C (refrigerated conditions) or 25 deg C/60% relative
      humidity and assayed for drug concentration at 0, 1, 2, 4, and 8 weeks. The
      method of preparation affected the chemical stability of omeprazole when stored
      at 25 deg C/60% relative humidity; it was stable for 4 weeks if prepared by the
      shaking method, but for only 1 week if prepared by the grinding method. For both
      methods, the suspension was stable for 8 weks if stored under refrigerated
      conditions. It is recommended that the shaking method be employed for
      extemporaneously compounded omeprazole suspensions, and that the prepared
      suspension be stored in the refrigerator. 

PMID- 23966481
TI  - Stability of pergolide mesylate oral liquid at room temerature.
AB  - Pergolide mesylate (proprietary name Permax) is used to treat equine Cushing's
      syndrome. Since pergolide mesylate has been removed from the market, the tablets
      are no longer available. Therefore, pergolide mesylate preparations have to be
      compounded for veterinary use. Compounded oral liquid formulations have been
      given arbitrary beyond-use dates of 14 days (aqueous) to 90 days (oil based). The
      goal of this study was to determine the stability of a 0.2 mg/mL pergolide oral
      liquid prepared according to a previousy published formulation and stored at room
      temperature. The sample preparation and the high-performance liquid
      chromatographic assay described in the United States Pharmacopeia-National
      Formulary were modified to treat the oral liquid as a suspension. The assay was
      evaluated prior to its use. A linear relationship was found between peak area and
      concentration with Rsquared values ranging for 0.989 to 0.999 for three of the
      sample calibration plots. The daily reproducibility and day-to-day variability of
      single injections of the assay were found to have relative standard deviations of
      1.26% and 3.52%, respectively. Analysis of the oral liquid and a blank oral
      liquid (without pergolide mesylate) exposed to acid and heat demonstrated that
      the excipients and degradation species did not interfere with the drug peak.
      Samples, in replicates of five, were stored at room temperature, then pulled at
      specific intervals (1, 2, 4, 8, 12, and 16 weeks) and stored at -80 deg C for
      assay at a later date. After 16 weeks at room temperature, the drug degraded to
      71% of its original concentration. The time to reach 90% potency (t90) of
      pergolide mesylate was calculated to be 6.5 weeks (45 days). Degradation studies
      at 35 deg C, 45 deg C, and 60 deg C are in progress. 

PMID- 23966482
TI  - Formulation optimization study for an immediate-release tablet.
AB  - A simple method based on statistical analysis was used to optimize an immediate
      release tablet formulation that includes a water soluble drug. The objective of
      this study was to optimize different factors to develop a tablet formulation that
      has good tablet characteristics (hardness of 85 to 90 Newtons), disintegration
      time between 3 to 6 minutes, and friability of less than 1%. The critical
      formulation/process factors were the type and concentration of microcrystalline
      cellulose, the ratio of lactose to microcrystalline cellulose, the concentration
      of croscarmellose, and the the compression force. A two-step approach was
      implemented. First an optimization study was performed to determine the type of
      microcrystalline cellulose and its ratio to lactose. Subsequently, a final
      optimization formulation study was performed based on the results obtained in the
      preliminary study. Data were analyzed using the SPSS 15 (Statistical Software for
      Social Sciences). The differences in means between the formulation and the
      targeted product were tested using the independent t-test. The optimization study
      gave the following results: croscarmellose 1%, anhydrous lactose: Avicel PH-302
      at a ratio of 3 to 1, magnesium stearate 0.25% compressed into tablets at a
      pressure of 2.5 tons. A high P value reflected no statistical difference with the
      reference product. A final formulation was scaled up to 52 tablets and product
      quality was confirmed. The new formulation was successfully developed using a
      simple two-step approach. The results of the study in terms of disintegration,
      hardness, and friability showed no statistically significant defference between
      the new and the targeted formulation. Statistical analysis provides a systemic
      approach and allows a rapid and effective way to compound an immediate-release
      tablet for a water-soluble drug. 

PMID- 23966483
TI  - Don't take your EHR to heaven, donate it to science: legal and research policies
      for EHR post mortem.
AB  - Recently, an important public debate emerged about the digital afterlife of any
      personal data stored in the cloud. Such debate brings also to attention the
      importance of transparent management of electronic health record (EHR) data of
      deceased patients. In this perspective paper, we look at legal and regulatory
      policies for EHR data post mortem. We analyze observational research situations
      using EHR data that do not require institutional review board approval. We
      propose creation of a deceased subject integrated data repository (dsIDR) as an
      effective tool for piloting certain types of research projects. We highlight
      several dsIDR challenges in proving death status, informed consent, obtaining
      data from payers and healthcare providers and the involvement of next of kin. 

PMID- 23966484
TI  - Rapid detection of Gram-positive organisms by use of the Verigene Gram-positive
      blood culture nucleic acid test and the BacT/Alert Pediatric FAN system in a
      multicenter pediatric evaluation.
AB  - Assays that expedite the reporting of organism identification and antibiotic
      susceptibility status in positive blood cultures can fast track interventions
      that improve clinical outcomes. We evaluated the Verigene Gram-positive blood
      culture nucleic acid test (BC-GP) in two pediatric hospitals. Positive BacT/Alert
      Pediatric FAN blood cultures with Gram-positive organisms were tested using the
      BC-GP in tandem with routine laboratory procedures. To test organisms
      underrepresented in the clinical blood culture evaluation, blood culture bottles
      were spiked with diluted organism suspensions at concentrations of 10 to 100 CFU
      per milliliter. A total of 249 Gram-positive bacterial isolates were recovered
      from 242 blood cultures. The BC-GP detected Staphylococcus aureus, methicillin
      susceptible S. aureus, and methicillin-resistant S. aureus with sensitivities of
      100%, 99%, and 100% and specificities of 100%, 100%, and 99.5%, respectively. The
      BC-GP detected Staphylococcus epidermidis, methicillin-susceptible S.
      epidermidis, and methicillin-resistant S. epidermidis with sensitivities of 95%,
      80%, and 96%, respectively, and 100% specificity. The BC-GP correctly identified
      14/15 cases of Enterococcus faecalis and Enterococcus faecium bacteremia and 9
      cases of Streptococcus pneumoniae. It misidentified 5/15 clinical blood cultures
      with Streptococcus mitis/Streptococcus oralis and 1/3 blood cultures spiked with
      Streptococcus anginosus group as S. pneumoniae. The BC-GP detected a case of
      Streptococcus pyogenes bacteremia but failed to detect 2/3 clinical blood
      cultures with Streptococcus agalactiae. BC-GP's rapid accurate detection of
      Staphylococcus spp., E. faecium, and E. faecalis and its ability to ascertain
      mecA, vanA, and vanB status may expedite clinical decisions pertaining to optimal
      antibiotic use. False-positive S. pneumoniae results may warrant reporting of
      only "Streptococcus spp." when this organism is reported by the BC-GP. 

PMID- 23966485
TI  - Detection of influenza H7N9 virus: all molecular tests are not equal.
AB  - The recent emergence of influenza A virus (H7N9) emphasizes the need for its
      rapid detection. While commercial nucleic acid amplification tests (NAATs) are
      commonly used to detect seasonal influenza virus, this study demonstrated that
      the analytical sensitivity of commercial assays is highly variable compared to
      that of CDC-based in-house NAATs for the detection of H7N9. 

PMID- 23966486
TI  - Serotype 5 pneumococci causing invasive pneumococcal disease outbreaks in
      Barcelona, Spain (1997 to 2011).
AB  - In this study, we analyzed the clinical and molecular epidemiology of invasive
      serotype 5 (Ser5) pneumococcal isolates in four teaching hospitals in the
      Barcelona, Spain, area (from 1997 to 2011). Among 5,093 invasive pneumococcal
      isolates collected, 134 (2.6%) Ser5 isolates were detected. Although the overall
      incidence of Ser5-related invasive pneumococcal disease (IPD) was low (0.25
      cases/100,000 inhabitants), three incidence peaks were detected: 0.63/100,000 in
      1999, 1.15/100,000 in 2005, and 0.37/100,000 in 2009. The rates of Ser5 IPD were
      higher among young adults (18 to 64 years old) and older adults (>64 years old)
      in the first two peaks, whereas they were higher among children in 2009. The
      majority (88.8%) of the patients presented with pneumonia. Comorbid conditions
      were present in young adults (47.6%) and older adults (78.7%), the most common
      comorbid conditions being chronic obstructive pulmonary disease (20.6% and 38.3%,
      respectively) and cardiovascular diseases (11.1% and 38.3%, respectively). The
      mortality rates were higher among older adults (8.5%). All Ser5 pneumococci
      tested were fully susceptible to penicillin, cefotaxime, erythromycin, and
      ciprofloxacin. The resistance rates were 48.5% for co-trimoxazole, 6.7% for
      chloramphenicol, and 6% for tetracycline. Two major related sequence types (STs),
      ST1223 (n = 65) and ST289 (n = 61), were detected. The Colombia(5)-ST289 clone
      was responsible for all the cases in the Ser5 outbreak in 1999, whereas the
      ST1223 clone accounted for 73.8% and 61.5% of the isolates in 2005 and 2009,
      respectively. Ser5 pneumococci are a frequent cause of IPD outbreaks in the
      community and involve children and adults with or without comorbidities. The
      implementation of the new pneumococcal conjugated vaccines (PCV10 and PCV13)
      might prevent such outbreaks. 

PMID- 23966487
TI  - Mortality in kittens is associated with a shift in ileum mucosa-associated
      enterococci from Enterococcus hirae to biofilm-forming Enterococcus faecalis and
      adherent Escherichia coli.
AB  - Approximately 15% of foster kittens die before 8 weeks of age, with most of these
      kittens demonstrating clinical signs or postmortem evidence of enteritis. While a
      specific cause of enteritis is not determined in most cases, these kittens are
      often empirically administered probiotics that contain enterococci. The
      enterococci are members of the commensal intestinal microbiota but also can
      function as opportunistic pathogens. Given the complicated role of enterococci in
      health and disease, it would be valuable to better understand what constitutes a
      "healthy" enterococcal community in these kittens and how this microbiota is
      impacted by severe illness. In this study, we characterized the ileum mucosa
      associated enterococcal community of 50 apparently healthy and 50 terminally ill
      foster kittens. In healthy kittens, Enterococcus hirae was the most common
      species of ileum mucosa-associated enterococci and was often observed to adhere
      extensively to the small intestinal epithelium. These E. hirae isolates generally
      lacked virulence traits. In contrast, non-E. hirae enterococci, notably
      Enterococcus faecalis, were more commonly isolated from the ileum mucosa of
      kittens with terminal illness. Isolates of E. faecalis had numerous virulence
      traits and multiple antimicrobial resistances. Moreover, the attachment of
      Escherichia coli to the intestinal epithelium was significantly associated with
      terminal illness and was not observed in any kitten with adherent E. hirae. These
      findings identify a significant difference in the species of enterococci cultured
      from the ileum mucosa of kittens with terminal illness compared to the species
      cultured from healthy kittens. In contrast to prior case studies that associated
      enteroadherent E. hirae with diarrhea in young animals, these controlled studies
      identified E. hirae as more often isolated from healthy kittens and adherence of
      E. hirae as more common and extensive in healthy kittens than in sick kittens. 

PMID- 23966488
TI  - Chronic rhinovirus infection in an adult with cystic fibrosis.
AB  - Rhinovirus is a common cause of exacerbations of cystic fibrosis (CF) and is
      usually considered a self-limiting infection. We report a case of chronic
      infection with rhinovirus A type 33 in a 43-year-old male with CF which has
      persisted for over 2 years. 

PMID- 23966489
TI  - Novel approach for improving sensitivity of microscopic detection of acid-fast
      bacilli (AFB) by use of the ReaSLR method.
AB  - The ReaSLR methodology developed for sputum processing is a novel, low-cost, and
      simple technique that has improved the sensitivity of smear microscopy for the
      diagnosis of tuberculosis (TB). Sample processing consists of rapid liquefaction
      of the sputum specimen with the ReaSLR reagent, followed by syringe filtration,
      concentration by centrifugation, and use of the sediment for smear microscopy.
      The performance of the ReaSLR kit was evaluated on 150 sputum samples and was
      compared with that of the modified Petroff method for sputum decontamination and
      concentration. Ziehl-Neelsen staining was performed for smear microscopy after
      processing by these two techniques; simultaneously, culture on Lowenstein-Jensen
      (LJ) medium was done to evaluate the two methods. The efficiency of smear
      microscopy was 18/150 (12%) with the modified Petroff method compared to 47/150
      (31.33%) with the ReaSLR method, and this difference was statistically
      significant (P < 0.001). The ReaSLR method for smear microscopy demonstrated a
      sensitivity and specificity of 90.47% and 91.6%, respectively, whereas the
      modified Petroff method showed a sensitivity and specificity of 40.47% and
      99.07%, respectively, compared to those of culture, which was used as the gold
      standard. With the newer ReaSLR method, the kappa coefficient (kappa) was 0.8,
      which implies an excellent positive agreement. The ReaSLR method was found to be
      more sensitive than the conventional method for sputum smear microscopy. The
      newer ReaSLR method holds promise for adoption in TB control programs across the
      globe, as it was found suitable for the laboratory diagnosis of pulmonary TB.
      Further large-scale studies are needed to evaluate other aspects of this method. 

PMID- 23966490
TI  - Identification, typing, and phylogenetic relationships of the main clinical
      Nocardia species in spain according to their gyrB and rpoB genes.
AB  - This study compares the identification, typing, and phylogenetic relationships of
      the most prevalent clinical Nocardia species in Spain, as determined via sequence
      analysis of their housekeeping genes gyrB and rpoB, with the results returned by
      the gold standard 16S rRNA method. gyrB and rpoB analyses identified Nocardia
      abscessus, N. cyriacigeorgica, N. farcinica, and the N. nova complex, species
      that together account for more than half of the human nocardiosis cases recorded
      in Spain. The individual discriminatory power of gyrB and rpoB with respect to
      intraspecies typing, calculated using the Hunter-Gaston discriminatory index
      (HGDI), was generally high (HGDI, 0.85 to 1), except for rpoB with respect to N.
      farcinica (HGDI, 0.71). Phylogenetically, different degrees of intra- and
      interspecies microheterogeneity were observed for gyrB and rpoB in a group of 119
      clinical strains. A single 16S haplotype was obtained for each species, except
      for the N. nova complex (8 types), while gyrB and rpoB were more polymorphic: N.
      abscessus had 14 and 18 haplotypes, N. cyriacigeorgica had 17 and 12, N.
      farcinica had 11 and 5, and the N. nova complex had 26 and 29 haplotypes,
      respectively. A diversity gradient was therefore seen, with N. farcinica at the
      bottom followed by N. abscessus and N. cyriacigeorgica in the middle and N. nova
      complex at the top. The complexity of the N. nova complex is highlighted by its
      six variations in the GyrB (126)AAAPEH motif. gyrB sequencing (with or without
      rpoB sequencing) offers a simple means for identifying the most prevalent
      Nocardia species in Spanish medical laboratories and for determining the
      intraspecific diversity among their strains. 

PMID- 23966491
TI  - Cutaneous listeriosis.
AB  - Cutaneous infections due to Listeria monocytogenes are rare. Typically,
      infections manifest as nonpainful, nonpruritic, self-limited, localized,
      papulopustular or vesiculopustular eruptions in healthy persons. Most cases
      follow direct inoculation of the skin in veterinarians or farmers who have
      exposure to animal products of conception. Less commonly, skin lesions may arise
      from hematogenous dissemination in compromised hosts with invasive disease. Here,
      we report the first case in a gardener that occurred following exposure to soil
      and vegetation. 

PMID- 23966492
TI  - Evaluation of the vitek 2 AST-N269 card for detection of meropenem resistance in
      imipenem-susceptible meropenem-resistant Enterobacteriaceae.

PMID- 23966494
TI  - Comparison of matrix-assisted laser desorption ionization-time of flight (maldi
      tof) mass spectrometry platforms for the identification of gram-negative rods
      from patients with cystic fibrosis.
AB  - We evaluated the performance of the Bruker Biotyper and the bioMerieux Vitek MS
      with both the SARAMIS v4.09 and Knowledge Base v2.0 databases for the
      identification of 203 non-glucose-fermenting Gram-negative rods that had
      previously been identified by 16S rRNA gene sequencing. Including those that
      underwent repeat testing, 96.6%, 90.1%, and 93.6% of isolates, respectively, had
      identifications that agreed with the previous identification. 

PMID- 23966493
TI  - Cluster of macrolide-resistant Mycoplasma pneumoniae infections in Illinois in
      2012.
AB  - Macrolide-resistant Mycoplasma pneumoniae is an increasing problem worldwide but
      is not well documented in the United States. We report a cluster of macrolide
      resistant M. pneumoniae cases among a mother and two daughters. 

PMID- 23966495
TI  - Tuberculosis-spoligo-rifampin-isoniazid typing: an all-in-one assay technique for
      surveillance and control of multidrug-resistant tuberculosis on Luminex devices.
AB  - As a follow-up of the "spoligoriftyping" development, we present here an
      extension of this technique which includes the detection of isoniazid resistance
      associated mutations in a new 59-plex assay, i.e., tuberculosis-spoligo-rifampin
      isoniazid typing (TB-SPRINT), running on microbead-based multiplexed systems.
      This assay improves the synergy between clinical microbiology and epidemiology by
      providing (i) mutation-based prediction of drug resistance profiles for patient
      treatment and (ii) genotyping data for tuberculosis (TB) surveillance. This third
      generation microbead-based high-throughput assay for TB runs on the Luminex 200
      system and on the recently launched MagPix system (Luminex, Austin, TX).
      Spoligotyping patterns obtained by the TB-SPRINT method were 100% (n = 85
      isolates; 3,655/3,655 spoligotype data points) concordant with those obtained by
      microbead-based and membrane-based spoligotyping. Genetic drug susceptibility
      typing provided by the TB-SPRINT method was 100% concordant with resistance locus
      sequencing (n = 162 for rpoB gene sequencing and n = 76 for katG and inhA
      sequencing). Considering phenotypic drug susceptibility testing (DST) as the
      reference method, the sensitivity and specificity of TB-SPRINT regarding
      Mycobacterium tuberculosis complex (n = 162 isolates) rifampin resistance were
      both 100%, and those for isoniazid resistance were 90.4% (95% confidence
      interval, 85 to 95%) and 100%, respectively. Used routinely in national TB
      reference and specialized laboratories, the TB-SPRINT assay should simultaneously
      improve personalized medicine and epidemiological surveillance of multidrug
      resistant (MDR) TB. This assay is expected to play an emerging role in public
      health in countries with heavy burdens of MDR TB and/or HIV/TB coinfection.
      Application of this assay directly to biological samples, as well as development
      for extensively drug-resistant (XDR) TB detection by inclusion of second-line
      antituberculosis drug-associated mutations, is under development. With
      bioinformatical methods and data mining to reduce the number of targets to the
      most informative ones, locally adapted formats of this technique can easily be
      developed everywhere. 

PMID- 23966497
TI  - Correlation between Clostridium difficile bacterial load, commercial real-time
      PCR cycle thresholds, and results of diagnostic tests based on enzyme immunoassay
      and cell culture cytotoxicity assay.
AB  - The impact of Clostridium difficile fecal loads on diagnostic test results is
      poorly understood, but it may have clinical importance. In this study, we
      investigated the relationship between C. difficile fecal load and the results of
      four assays: a glutamate dehydrogenase (GDH) enzyme immunoassay (EIA), a toxin
      A/B antigen EIA (ToxAB), a cell culture cytotoxicity assay (CCA), and PCR
      targeting the tcdB gene. We also compared the PCR cycle threshold (CT) with the
      results of quantitative culture using Spearman's rank correlation coefficient.
      Finally, we sequenced the genomes of 24 strains with different detection
      profiles. A total of 203 clinical samples harboring toxigenic C. difficile were
      analyzed and sorted into one of four groups: 17 PCR(+) (group 1), 37 PCR(+)
      GDH(+) (group 2), 24 PCR(+) GDH(+) CCA(+) (group 3), and 125 PCR(+) GDH(+)
      ToxAB(+) (group 4). The overall median fecal load in log10 CFU/g was 6.67
      (interquartile range [IQR], 5.57 to 7.54). The median fecal bacterial load of
      groups 1, 2, 3, and 4 were 4.15 (IQR, 3.00 to 4.98), 5.74 (IQR, 4.75 to 6.16),
      6.20 (IQR, 5.23 to 6.80), and 7.08 (IQR, 6.35 to 7.83), respectively. Group 1
      samples had lower fecal loads than those from each of the other groups (P <
      0.001). Group 2 samples had lower fecal loads than those from groups 3 and 4 (P <
      0.001). There was a significant correlation between PCR CT and fecal loads (rho =
      -0.697; P < 0.001). NAP1 strains were associated with the detection of toxins by
      EIA or CCA (P = 0.041). This study demonstrates an association between C.
      difficile fecal load and the results of routinely used diagnostic tests. 

PMID- 23966498
TI  - Rapid and direct real-time detection of blaKPC and blaNDM from surveillance
      samples.
AB  - We assessed the performance of a duplex real-time PCR assay for bla(KPC) and
      bla(NDM) performed directly (D-PCR) on perianal and perirectal swabs and stool.
      Spiked specimens and 126 clinical surveillance swabs (comprising a sensitivity
      panel of 46 perirectal double swabs previously determined to be culture positive
      for bla(KPC)-PCR-positive Enterobacteriaceae and a specificity panel of 80
      perianal swabs from patients at risk of carbapenemase-producing
      Enterobacteriaceae [CPE] colonization) were studied. For the surveillance swabs,
      D-PCR was compared to PCR after broth enrichment (BE-PCR) and two culture-based
      methods: the HardyCHROM ESBL agar (HC-A) and the CDC screening (CDC-A) methods.
      PCR was performed on morphologically distinct colonies that were isolated by
      culture. All of the initial PCR testing was done without extraction using a
      simple lysis procedure. The analytical sensitivities of D-PCR for bla(KPC) were 9
      CFU/MUl (for swabs) and 90 CFU/MUl (for stool), and for bla(NDM), it was 1.9
      CFU/MUl (for both swabs and stool). In the clinical sensitivity panel, D-PCR and
      BE-PCR were initially positive for bla(KPC) in 41/46 (89.1%) and 43/46 (93.5%)
      swabs, respectively. The swabs that were initially negative by D-PCR (n = 5) and
      BE-PCR (n = 3) were visibly stool soiled; all swabs were bla(KPC) positive upon
      repeat testing after lysate extraction. The CDC-A and HC-A yielded bla(KPC)
      positive Enterobacteriaceae from 36/46 (78.3%) and 35/46 (76.1%) swabs,
      respectively (sensitivities of D-PCR/BE-PCR postextraction of soiled specimens
      versus HC-A, P = 0.0009, and versus CDC-A, P = 0.0016). All swabs in the
      specificity panel were negative for CPE by all four methods. D-PCR allows for the
      timely detection of bla(KPC) and bla(NDM) carriage with excellent sensitivity
      when specimens visibly soiled with stool undergo preparatory extraction.

PMID- 23966499
TI  - Evidence for recombination between pandemic GII.4 norovirus strains New Orleans
      2009 and Sydney 2012.
AB  - During 2012, a novel pandemic GII.4 norovirus variant, Sydney 2012, emerged
      worldwide. A signature of the variant was a GII.Pe ORF1, in association with
      GII.4 Apeldoorn 2008-like ORF2-ORF3 genes. We report the detection of recombinant
      GII.4 Sydney 2012 strains, possessing the ORF1 gene of the former pandemic
      variant New Orleans 2009. 

PMID- 23966500
TI  - Comparative evaluation of BD Phoenix and vitek 2 systems for species
      identification of common and uncommon pathogenic yeasts.
AB  - The BD Phoenix system was evaluated for species-level identification of yeasts
      (250 clinical isolates) and compared with the Vitek 2 system, using ribosomal
      internal transcribed spacer (ITS) sequence analysis as the gold standard.
      Considering only the species included in each system's database, 96.3% (236/245)
      and 91.4% (224/245) of the isolates were correctly identified by BD Phoenix and
      Vitek 2, respectively. 

PMID- 23966496
TI  - Emergence, circulation, and spatiotemporal phylogenetic analysis of
      coxsackievirus a6- and coxsackievirus a10-associated hand, foot, and mouth
      disease infections from 2008 to 2012 in Shenzhen, China.
AB  - Sporadic hand, foot, and mouth disease (HFMD) outbreaks and other infectious
      diseases in recent years have frequently been associated with certain human
      enterovirus (HEV) serotypes. This study explored the prevalences and genetic
      characteristics of non-HEV71 and non-coxsackievirus A16 (CV-A16) human
      enterovirus-associated HFMD infections in Shenzhen, China. A total of 2,411
      clinical stool specimens were collected from hospital-based surveillance for HFMD
      from 2008 to 2012. The detection of HEV was performed by real-time reverse
      transcription-PCR (RT-PCR) and RT-seminested PCR, and spatiotemporal phylogenetic
      analysis was performed based on the VP1 genes. A total of 1,803 (74.8%) strains
      comprising 28 different serotypes were detected. In the past 5 years, the
      predominant serotypes were HEV71 (60.0%), followed by CV-A16 (21.2%) and two
      uncommon serotypes, CV-A6 (13.0%) and CV-A10 (3.3%). However, CV-A6 replaced CV
      A16 as the second most common serotype between 2010 and 2012. As an emerging
      pathogen, CV-A6 became as common a causative agent of HFMD as HEV71 in Shenzhen
      in 2012. Phylogenetic analysis revealed that little variation occurred in the
      Chinese HEV71 and CV-A16 strains. The genetic characteristics of the Chinese CV
      A6 and CV-A10 strains displayed geographic differences. The CV-A6 and CV-A10
      strains circulating in Shenzhen likely originated in Europe. It was found that
      human enteroviruses have a high mutation rate due to evolutionary pressure and
      frequent recombination (3.2 * 10(-3) to 6.4 *10(-3) substitutions per site per
      year for HEV71, CV-A6, CV-A16, and CV-A10). Since certain serotypes are potential
      threats to the public health, this study provides further insights into the
      significance of the epidemiological surveillance of HFMD. 

PMID- 23966501
TI  - Anal human papillomavirus genotype distribution in HIV-infected men who have sex
      with men by geographical origin, age, and cytological status in a Spanish cohort.
AB  - Knowledge of human papillomavirus (HPV) type distribution in populations at risk
      for anal cancer is needed. Here, we describe the anal HPV genotype distribution
      in a large Spanish cohort (Cohort of the Spanish HIV Research Network HPV [CoRIS
      HPV]) of HIV-positive men who have sex with men (MSM) according to geographical
      origin, age, and cytological status. A cross-sectional analysis of baseline data
      from 1,439 HIV-infected MSM (2007 to 2012) was performed. Anal HPV genotyping was
      performed using the Linear Array HPV genotyping test. Descriptive analyses of
      subject characteristics, prevalences, and 95% confidence intervals (CI) were
      performed. The global prevalences of HPV, high-risk HPV (HR-HPV), and low-risk
      HPV (LR-HPV) types were 95.8%, 83.0%, and 72.7%, respectively. Among the HR-HPV
      types, HPV16 was the most common, followed by HPV59, -39, -51, -18, and -52. The
      prevalence of multiple HR-HPV infections was 58.5%. There were no differences in
      the crude analyses between Spanish and Latin-American MSM for most HPV types, and
      a peak in prevalence for most HPV types was seen in patients in their late
      thirties. Globally and by specific HPV groups, men with abnormal anal cytologies
      had a higher prevalence of infection than those with normal cytologies. This
      study has the largest number of HIV-positive MSM with HPV genotype data analyzed
      according to cytological status as far as we know. The information gained from
      this study can help with the design of anal cancer prevention strategies in HIV
      positive patients. 

PMID- 23966502
TI  - Is hydrogen cyanide a marker of Burkholderia cepacia complex?
AB  - Biofilm cultures of Burkholderia cepacia complex (BCC) infection have been found
      to generate the nonvolatile cyanide ion. We investigated if gaseous hydrogen
      cyanide (HCN) was a marker of BCC infection. Selected ion flow tube mass
      spectrometry analysis showed HCN was not elevated in the headspace of planktonic
      or biofilm cultures or in the exhaled breath of adult cystic fibrosis patients
      with chronic BCC infection. HCN is therefore not an in vitro or in vivo marker of
      BCC. 

PMID- 23966503
TI  - Enhanced diagnostic yields of bacteremia and candidemia in blood specimens by PCR
      electrospray ionization mass spectrometry.
AB  - A prospective study was performed to determine the value of direct molecular
      testing of whole blood for detecting the presence of culturable and unculturable
      bacteria and yeasts in patients with suspected bloodstream infections. A total of
      464 adult and pediatric patients with positive blood cultures matched with 442
      patients with negative blood cultures collected during the same period were
      recruited during a 10-month study. PCR amplification coupled with electrospray
      ionization mass spectrometry (PCR-ESI-MS) plus blood culture reached an overall
      agreement of 78.6% in the detection and species-level identification of bacterial
      and candidal pathogens. Of 33 culture-negative/PCR-ESI-MS-positive specimens, 31
      (93.9%) were judged to be truly bacteremic and/or candidemic based on a medical
      chart review and analytical metrics. Among the 15 culture-positive specimens in
      which PCR-ESI-MS detected additional bacterial or yeast species, 66.7% and 20.0%
      of the additional positive specimens by PCR-ESI-MS were judged to be truly or
      possibly bacteremic and/or candidemic, respectively. Direct analysis of blood
      samples by PCR-ESI-MS rapidly detects bacterial and yeast pathogens in patients
      with bloodstream infections. When used in conjunction with blood culture, PCR-ESI
      MS enhances the diagnostics of septicemia by shortening test turnaround time and
      improving yields. 

PMID- 23966504
TI  - Improvement rate of acute otitis media caused by Haemophilus influenzae at 1 week
      is significantly associated with time to recovery.
AB  - Acute otitis media (AOM) is the most common upper respiratory tract infection in
      childhood. Children with AOM were enrolled at Tohoku Rosai Hospital between July
      2006 and June 2011 if their middle ear fluid cultures after tympanocentesis
      yielded only Haemophilus influenzae. The susceptibilities of the isolates to
      ampicillin were determined, and microtiter biofilm assays and invasion assays
      using BEAS-2B cells were performed. The association between these bacterial
      characteristics and clinical relapses of AOM and treatment failures was
      evaluated. Seventy-four children (39 boys and 35 girls) with a median age of 1
      year (interquartile range [IQR], 0.25 to 2 years) were enrolled. Among 74 H.
      influenzae isolates, 37 showed intermediate resistance or resistance to
      ampicillin (MIC, >= 2 MUg/ml). In the microtiter biofilm assay, the median
      optical density at 600 nm (OD600) was 0.68 (IQR, 0.24 to 1.02), and 70 isolates
      formed biofilms. The median invasion rate was 15% (IQR, 0 to 10%), and 46
      isolates invaded BEAS-2B cells. Relapses and treatment failures occurred in 19
      and 6 children, respectively. There was no significant difference in the invasion
      rates between patients with and those without relapses or treatment failures.
      Also, there was no significant association between biofilm formation and relapse
      or treatment failure. The improvements in the severity scores after 1 week were
      significantly associated with the recovery time (P < 0.0001). We did not identify
      any significant association between relapse or treatment failure and bacterial
      factors. AOM has a multifactorial etiology, and this may explain why we could not
      find a significant association. An improvement in the severity score after 1 week
      of treatment may be a useful predictor of the outcome of AOM.

PMID- 23966505
TI  - Impact of blood volume, tube shaking, and incubation time on reproducibility of
      QuantiFERON-TB gold in-tube assay.
AB  - Gamma interferon (IFN-gamma) release assays (IGRAs) are functional assays used
      serially to measure the efficacy of novel tuberculosis (TB) vaccines and to
      screen health care workers for latent tuberculosis infection (LTBI). However,
      studies have shown nonreproducible IGRA results. In this study, we investigated
      the effects of blood volume (0.8, 1.0, and 1.2 ml), tube shaking (gentle versus
      vigorous), and incubation duration (16, 20, and 24 h) on the reproducibility of
      QuantiFERON-TB Gold In-Tube (QFT-GIT) results for 50 subjects (33 uninfected and
      17 infected). The median IFN-gamma TB response (TB antigen [Ag] minus nil value)
      was significantly higher with 0.8 ml blood (1.04 IU/ml) than with 1.0 ml (0.85
      IU/ml; P = 0.002) or 1.2 ml (0.49 IU/ml; P < 0.001) for subjects with LTBI.
      Compared with 0.8 ml (11.8%), there were larger proportions of false-negative
      results with 1.0 ml (29.4%; P = 0.2) and 1.2 ml (41.2%; P = 0.05) of blood for
      infected subjects. Blood volume did not significantly change the proportions of
      positive results in uninfected controls. Compared with gentle shaking, vigorous
      shaking increased the median IFN-gamma response in nil (0.04 versus 0.06 IU/ml; P
      < 0.001) and TB Ag (0.12 versus 0.24 IU/ml; P = 0.004) tubes and increased TB
      responses (TB Agvigorous minus nilgentle) (0.02 versus 0.08 IU/ml; P = 0.004).
      The duration of incubation did not have a significant impact on the proportion of
      positive results in uninfected or infected subjects. This study identified blood
      volume and tube shaking as novel preanalytical sources of variability which
      require further standardization in order to improve the quality and
      reproducibility of QFT-GIT results. 

PMID- 23966506
TI  - Application of matrix-assisted laser desorption ionization-time of flight mass
      spectrometry for identification of the fastidious pediatric pathogens
      Aggregatibacter, Eikenella, Haemophilus, and Kingella.
AB  - The accuracy of matrix-assisted laser desorption-ionization time of flight mass
      spectrometry (MALDI-TOF MS) in the identification of Haemophilus,
      Aggregatibacter, Cardiobacterium, Eikenella, and Kingella (HACEK) species was
      compared to that of phenotypic methods (Remel RapID and Vitek 2). Overall, Vitek
      MS correctly identified more isolates, incorrectly identified fewer isolates, and
      failed to identify fewer isolates than both phenotypic methods. 

PMID- 23966508
TI  - Evaluation of an enzyme immunoassay for detection of Histoplasma capsulatum
      antigen from urine specimens.
AB  - Detection of Histoplasma capsulatum urinary antigen (UAg) is important for the
      initial diagnosis of infection and for monitoring of patient responses to
      antifungal therapy. This study evaluated an analyte-specific reagent (ASR) enzyme
      immunoassay (EIA) for the detection of H. capsulatum UAg from Immuno Mycologics,
      Inc. (IMMY) (Norman, OK) in comparison with routine testing with the MiraVista
      (MVista) H. capsulatum quantitative EIA (MiraVista Diagnostics, Indianapolis,
      IN). Using prospectively collected urine specimens (n = 1,003), we observed an
      overall percent agreement between the two assays of 97.6% (979/1,003 samples).
      Compared with the MVista EIA, the sensitivity and specificity of the IMMY ASR EIA
      were 64.5% (40/62 samples) and 99.8% (939/941 samples), respectively, using a
      cutoff value of 0.5 ng/ml. Based on available clinical histories for 23/24
      discordant samples, 5 IMMY assay-negative/MVista assay-positive samples were
      considered falsely positive. Furthermore, 10/23 discordant samples were positive
      by the MVista EIA but were below the limit of quantitation (<0.4 ng/ml). The
      clinical significance of these low positive results in the MVista EIA is unclear.
      In addition to the prospective study, we tested 11 urine specimens collected from
      patients with culture-confirmed Histoplasma infections, and 100% (11/11 samples)
      were positive by the IMMY ASR EIA. In conclusion, the IMMY ASR EIA may offer an
      alternative approach for the detection of Histoplasma UAg. Additional prospective
      studies are needed to better characterize the performance of the IMMY ASR EIA in
      conjunction with clinical and laboratory findings. 

PMID- 23966507
TI  - Validation of an rpoB gene PCR assay for detection of Tropheryma whipplei: 10
      years' experience in a National Reference Laboratory.
AB  - The performance of a real-time PCR assay targeting the Tropheryma whipplei rpoB
      gene was evaluated using test strains and 1,236 clinical specimens in a national
      reference laboratory. The novel rpoB-PCR assay proved to be specific, revealed
      improved analytical sensitivity, and substantially accelerated detection of T.
      whipplei DNA in clinical specimens. 

PMID- 23966509
TI  - Pharmacodynamics of doxycycline and tetracycline against Staphylococcus
      pseudintermedius: proposal of canine-specific breakpoints for doxycycline.
AB  - Doxycycline is a tetracycline that has been licensed for veterinary use in some
      countries, but no clinical breakpoints are available for veterinary pathogens.
      The objectives of this study were (i) to establish breakpoints for doxycycline
      and (ii) to evaluate the use of tetracycline as a surrogate to predict the
      doxycycline susceptibility of Staphylococcus pseudintermedius isolates. MICs and
      inhibition zone diameters were determined for 168 canine S. pseudintermedius
      isolates according to Clinical and Laboratory Standards Institute (CLSI)
      standards. Tetracycline resistance genes were detected by PCR, and time-kill
      curves were determined for representative strains. In vitro pharmacodynamic and
      target animal pharmacokinetic data were analyzed by Monte Carlo simulation (MCS)
      for the development of MIC interpretive criteria. Optimal zone diameter
      breakpoints were defined using the standard error rate-bounded method. The two
      drugs displayed bacteriostatic activity and bimodal MIC distributions.
      Doxycycline was more active than tetracycline in non-wild-type strains. MCS and
      target attainment analysis indicated a certainty of >= 90% for attaining an area
      under the curve (AUC)/MIC ratio of >25 with a standard dosage of doxycycline (5
      mg/kg of body weight every 12 h) for strains with MICs of <= 0.125 MUg/ml.
      Tetracycline predicted doxycycline susceptibility, but current tetracycline
      breakpoints were inappropriate for the interpretation of doxycycline
      susceptibility results. Accordingly, canine-specific doxycycline MIC breakpoints
      (susceptible, <= 0.125 MUg/ml; intermediate, 0.25 MUg/ml; resistant, >= 0.5
      MUg/ml) and zone diameter breakpoints (susceptible, >= 25 mm; intermediate, 21 to
      24 mm; resistant, <= 20 mm) and surrogate tetracycline MIC breakpoints
      (susceptible, <= 0.25 MUg/ml; intermediate, 0.5 MUg/ml; resistant, >= 1 MUg/ml)
      and zone diameter breakpoints (susceptible, >= 23 mm; intermediate, 18 to 22 mm;
      resistant, <= 17 mm) were proposed based on the data generated in this study.

PMID- 23966510
TI  - Comparison of 14 molecular assays for detection of Mycobacterium tuberculosis
      complex in bronchoalveolar lavage fluid.
AB  - We compared 14 molecular assays for their ability to detect the Mycobacterium
      tuberculosis complex in bronchoalveolar lavage fluid samples. Three approaches
      were followed. First, by using DNA from Mycobacterium bovis BCG, we determined
      the detection limits of the assays using routine molecular methods. Second, in
      order to determine the analytical sensitivities of the assays, we added one of
      four M. tuberculosis isolates with various numbers of the insertion sequence
      IS6110 to N-acetyl-l-cysteine (NALC)-NaOH-treated bronchoalveolar lavage fluid
      samples in dilutions of 1:10 to 1:10,000,000. Third, intertest variabilities were
      measured and defined by the standard deviations for the quantitation cycle (Cq)
      values of three positive test results per dilution per assay. The 14 assays
      tested had similar analytical sensitivities, except for GeneXpert, which had an
      analytical sensitivity that was 10- to 100-fold lower than that of the other
      assays. The MP MTB/NTM test and the in-house TaqMan-10 revealed the best
      performances for the detection limit and had the highest analytical
      sensitivities. Most of the tests performed well regarding detection limit and
      analytical sensitivity for the detection of the M. tuberculosis complex in serial
      dilutions, and the differences were small. The MP MTB/NTM and the in-house TaqMan
      10 assays revealed the best, and GeneXpert the worst, overall performances. 

PMID- 23966511
TI  - A convenient method to screen for carbapenemase-producing Pseudomonas aeruginosa.
AB  - A combined-disk method using imipenem and cloxacillin was evaluated to
      discriminate between carbapenemase-producing (n = 56) and nonproducing (n = 62)
      strains of Pseudomonas aeruginosa. With a cloxacillin load of 4,000 MUg/disk,
      this very simple method showed a sensitivity and a specificity of 100%,
      irrespective of the type of carbapenemase produced. 

PMID- 23966513
TI  - Development of a loop-mediated isothermal amplification assay targeting the mpb64
      gene for diagnosis of intraocular tuberculosis.
AB  - A loop-mediated isothermal amplification (LAMP) assay targeting the mpb64 gene
      for the diagnosis of intraocular tuberculosis was highly specific (100%),
      sensitive (85.7%), rapid, and easy to perform. The LAMP assay can be an
      alternative to conventional PCR for the diagnosis of ocular tuberculosis in
      resource-limited settings. 

PMID- 23966512
TI  - Molecular characterization of herpes simplex virus 2 strains by analysis of
      microsatellite polymorphism.
AB  - The complete 154-kbp linear double-stranded genomic DNA sequence of herpes
      simplex virus 2 (HSV-2), consisting of two extended regions of unique sequences
      bounded by a pair of inverted repeat elements, was published in 1998 and since
      then has been widely employed in a wide range of studies. Throughout the HSV-2
      genome are scattered 150 microsatellites (also referred to as short tandem
      repeats) of 1- to 6-nucleotide motifs, mainly distributed in noncoding regions.
      Microsatellites are considered reliable markers for genetic mapping to
      differentiate herpesvirus strains, as shown for cytomegalovirus and HSV-1. The
      aim of this work was to characterize 12 polymorphic microsatellites within the
      HSV-2 genome by use of 3 multiplex PCR assays in combination with length
      polymorphism analysis for the rapid genetic differentiation of 56 HSV-2 clinical
      isolates and 2 HSV-2 laboratory strains (gHSV-2 and MS). This new system was
      applied to a specific new HSV-2 variant recently identified in HIV-1-infected
      patients originating from West Africa. Our results confirm that microsatellite
      polymorphism analysis is an accurate tool for studying the epidemiology of HSV-2
      infections. 

PMID- 23966515
TI  - The physiologic role and use of estriol.
AB  - Obtaining estrogen balance with a physiologic estriol and estradiol ratio is an
      important aspect of physiologic bioidentical hormone restoration therapy. Risks,
      including that of breast cancer, should be minimized while attempting to obtain
      the protective benefits and symptom management with therapy. EStriol plays a
      central role in protecting against breast cancer and should be considered an
      integral part of therapy for any patient with lower than normal physiologic
      levels. 

PMID- 23966514
TI  - Gallibacterium anatis bacteremia in a human.
AB  - We describe the first case of bacteremia due to Gallibacterium anatis. The
      patient, a 26-year-old woman, developed bacteremia and diarrhea. The origin of
      infection was possibly due to a diet contaminated by G. anatis in this highly
      immunocompromised patient. 

PMID- 23966516
TI  - Hormone treatment options for males: what to do for men with low testosterone.
AB  - Male hypogonadism is a condition that is receiving increasing medical scrutiny,
      resulting in research producing results favorable to the consideration of
      maintaining physiological levels of testosterone. As healthcare professionals
      interested in the health and welfare of a significant portion of the population,
      surely compounding pharmacists are interested in what can be done for men with
      this condition to help these patients improve their quality of life and long-term
      health. This article discussed the various ways that men's testosterone levels
      can be raised and provides insight into the importance of androgen-estrogen
      balance. 

PMID- 23966517
TI  - Saliva tests, part 1: clinical use, elements of testing, and guidelines for
      posttreatment interpretation.
AB  - Saliva is an excellent medium for the measurement of the biologically active
      fraction of steroid hormones in the bloodstream because it is a natural
      ultrafiltrate of blood, and steroids not bound by carrier proteins in the blood
      freely diffuse into saliva. The baseline measurement of hormone levels in saliva
      provides an accurate assessment and can be used to identify or monitor a number
      of clinical conditions, including climacteric changes in perimenopausal or
      postmenopausal women, adrenal disorders such as Addison's disease or Cushing's
      disease, and androgen deficiency in men and women, the age-related decrease of
      hormones such as testosterone and dehydroepiandrosterone can also be assessed and
      monitored. When compared with serum testing, saliva testing offers several
      advantages. Saliva collection is simple, noninvasive, stress free, painless, and
      safe for the patient and practitioner. The collection time for saliva testing is
      more controllable than that for serum testing. The transport of saliva samples
      for assessment can be accomplished inexpensively via the U.S. Postal Service
      because hormones are stable in saliva for three weeks at room temperature, and
      the cost of that testing is covered by many insurance plans. In this first of a
      two-part series, we discuss the clinical use and basic elements of saliva testing
      and provide guidelines for postreatment interpretation by compounding
      pharmacists. 

PMID- 23966518
TI  - Preventing nonmicrobiologic airborne contamination in the compounding pharmacy:
      ensuring a safe environment for compounders, staff, and clients.
AB  - Preventing and minimizing exposure to nonmicrobiologic airborne contaminants in a
      compounding pharmacy protects the health of pharmacy staff and clients. The
      inhalation of hazardous substances has been linked to the development of diseases
      and disorders that range from cancer to infertility. Although a workplace
      environmental exposure level has been established for some antibiotics at the
      time of this writing there were no exposure limits recommended by the National
      Institue for Occupational Safety and Health or permitted by the Occupational
      Safety and Health Administration for hazardous drugs or pharmaceutical compounds,
      nor were threshold limit values for those substances specified by the American
      Conference of Governmental Industrial Hygienists. For that reason, an evaluation
      of environmental air quality performed by an industrial hygienist can yield
      valuable information that will reassure staff or provide the basis for remedial
      action. This report describes the assessment by an industrial hygienist of
      airborne hormone levles in a compounding pharmacy and reviews the results of that
      analysis. 

PMID- 23966519
TI  - Compounding naltrexone for the treatment of autism.
AB  - Autism is a complex disorder that affects children. Children who present with
      symptoms of autism require a comprehensive evaluation by a multidisciplinary team
      including a psychologist, neurologist, psychiatrist, speech therapist, and other
      professionals who diagnose children with autism spectrum disorders. Following the
      diagnosis, a treatment plan is developed, which in most cases involve educational
      and behavioral interventions and medications. The multidisciplinary team then
      expands to a team of professionals to treat the disorder, the team of which
      includes a pharmacist. Anxiety, depression, obsessive-compulsive disorder,
      behavioral problems, seizures, impulsivity, and hyperactivity are the main
      symptoms of autism that have in many cases been successfully minimized and in
      some cases alleviated by proper medication. 

PMID- 23966520
TI  - Preparing nonsterile and sterile hazardous compounds in an institutional setting.
AB  - All healthcare facilites are different, and there are no comprehensive guidelines
      or United States Pharmacopeial standards that will address all of a facility's
      needs. All physicians and healthcare professionals at a facility need to work
      together and rely on credible published guidelines, state and federal
      regulations, their own professional judgment, experience, and common sense to
      create their own comprehensive program for handling hazardous drugs and
      chemicals. Some of the subjects dicussed in this article as they pertain to the
      preparation of nonsterile and sterile hazardous compounds in an institutional
      setting are: personnel and training; establishing policies and procedures;
      environmental issues; decontamination, deactivation, and disinfecting; and
      containment and disposal. 

PMID- 23966521
TI  - Safety of maternal testosterone therapy during breast feeding.
AB  - This article is an adaptation of an abstract/poster presentaton made at the 13th
      International Congress on Steroidal Hormones and Hormones and Cancer, Quebec
      City, Canada (September 2008), concerning the topic of breast feeding as a
      contraindication to testosterone therapy. The purpose of the presentation and
      this article is to provide a summary of the findings of a study that was
      conducted to evaluate maternal absorption of testosterone and its excretion into
      breast milk by using three methods of delivery: sublingual drops, vaginal cream,
      and pellet implant. Testosterone was measurable in maternal blood by all three
      methods of delivery. No significanat increase of testosterone was seen in breast
      milk when testosterone was delivered by vaginal cream, sublingual drops, or
      subcutaneous pellet implant. Testosterone was very low in infant blood at
      baseline and during testosterone therapy by pellet implant. There was no adverse
      clinical affects in the infant after seven months of continuous testosterone
      therapy to the mother by subcutaneous pellet implant. Testosterone delivered by
      sublingual drops, vaginal cream, and pellet implant was absorbed but not
      measurably excreted into breast milk. Testosterone, delivered by a 100-mg
      subcutaneous pellet implant, was effective in relieving symptoms of testosterone
      deficiency and therapy is safe for the breast-fed infant. Testosterone by pellet
      implant may be a safer and more physiologic alternative to psychotropic
      medications. 

PMID- 23966522
TI  - Quality Control, Quality Assurance, and Quality Improvement-What is the
      Difference and Why Should Compounding Pharmacies Care?
AB  - This article provides scenarios of three different pharmacies in the areas of
      quality control, quality assurance, and quality improvement. The scenarios show
      the importance that each pharmacy placed on a problem of dented capsules and the
      potential impact that an unresolved problem can have on a compounding pharmacy's
      business. Although this article focuses on one particular procedure, the purpose
      of th article is to help pharmacists understand the differences between quality
      control, quality assurance, and quality improvement. 

PMID- 23966523
TI  - Basics of compounding: considerations for implementing United States pharmacopeia
      chapter 797 pharmaceutical compounding-sterile preparations, part 14:
      environmental quality and control (continued).
AB  - The design and location of the primary engineering controls within a compounding
      facility in order to maitain an expected controlled environment is well worth the
      time and expense involved. If the airflow within the compounding area is not
      properly designed and maintained, the results can be tragic to not only the
      compounding personnel but to those patients for whom the preparations are being
      compounded. Knowledge of the placement of primary engineering controls, air
      sampling, cleaning and disinfecting, and additional personnel requirements in the
      area of sterile compounding are essential. Once the guidelines have been studied,
      compounding personnel should apply practicality and common sense to avoid
      problems with compounded sterile preparations. 

PMID- 23966524
TI  - Quality of Progesterone Suppositories Prepared by FIRST-Progesterone Vaginal
      Suppository 50 Kit or Traditional Compounding Method: In Vitro Comparison.
AB  - The objective of this study was to compare the quality of progesterone
      suppositories prepared by using the FIRST-Progesterone Vaginal Suppository Kit to
      that of progesterone suppositories compounded extemporaneously by using the
      traditional method. The comparison parameters were weight variation, content
      uniformity, pH, yield, and compounding time. Each of five compounders prepared
      two batches, one batch using each method. The results indicate that the quality
      of the suppositories prepared by both methods including weight variation and
      content uniformity, fell within the United States Pharmacopeial accepted limits
      (+/- 10% of the label concentration). However, preparation time and yield were
      significantly different. The time spent compounding the suppositories with the
      FIRST-Progesterone Vaginal Suppository 50 kit was significantly shorter (five
      times shorter) than spent compounding the suppositories by the traditional method
      (P-less than 0.05). Although all compounders were advised to use an extra 10%
      during traditional compounding, three of the compounders failed to fill the
      prescribed number and ended with fewer suppositories than required. The reasons
      for this deficiency were either conventional mold leakage or spilling during mold
      filling. 

PMID- 23966525
TI  - Women's Perspective on Progesterone: A Qualitative Study Conducted in Australia.
AB  - This study explored the perspective of women using compounded progesterone
      preparations. Semi-structured interviews were conducted in Victoria, Australia
      with eight self-selected women who were dispensed a progesterone-only
      preparation. Participating women gained symptome relief for migraine, painful
      breasts, mood swings, bloating, hot flushes, and other conditions. The
      participants also experienced unexpected benefits such as improvement in
      irregular and painful periods, relief from cystitis, or increased libido, without
      any reported negative side effects. The participants appreciated the ability to
      adjust the dose and dosage form to their individual requirements and held a
      positive perception of progesterone as a "natural" product. Accessibility of
      progesterone treatment is limited due to the limited number of doctors that have
      knowledge about the treatment, little information available for lay people, and
      cost. Participants who had been treated with progesterone were willing to share
      their experience with others, and many heard about progesterone therapy from
      their social contacts. The cost of progesterone therapy, which was often more
      expensive than traditional hormone replacement therapy, was outweighed by the
      benefits received. These women found that progesterone treatment, although hard
      to access, was beneficial over conventional therapy. 

PMID- 23966526
TI  - Basics of compounding: considerations for implementing United States pharmacopeia
      chapter 797 pharmaceutical compounding-sterile preparations, part 15: personnel
      training, cleansing, and garbing.
AB  - Proper cleansing techniques must be followed by compounding personnel, the
      purpose of which is to eliminate microbial residues that could contaminate
      compounded sterile preparations. Personnel must be highly competent and motivated
      to perform the aseptic manipulations of compounding sterile preparations,
      ingredients, and devices without mistake. For personnel to achieve the level of
      competency and the motivation required for properly compounded sterile
      preparations, they must be thoroughly trained not only on compounding procedures,
      but on all aspects of cleansing and garbing. This article discusses the
      requirements provided within the United States Pharmcopeia concerning personnel
      training, cleansing, and garbing, as well as a discussion on good compounding
      practices as they relate to each of these issues.

PMID- 23966527
TI  - Chemical stability of scopolamine hydrobromide nasal solution.
AB  - The chemical stability of scopolamine hydrobromide in nasal solution has been
      studied by using a stability-indicating high-performance liquid chromatographic
      assay method that was developed in our laboratory. The concentrations of the drug
      were directly related to peak heights, and the percent relative standard
      deviation based on five injections was 0.4. The products of decomposition and
      excipients present in the dosage forms did not interfere with the developed assay
      method. The nasal solution was stable for at least 42 days when stored in amber
      colored glass bottles at room temperature. The physical appearance and the pH
      value of the nasal solution did not change during the study period. 

PMID- 23966528
TI  - Compounding solutions for exotic and nondomesticated fauna in australia: an
      investigative study.
AB  - Veterinarians face many challenges during routine administration of medication to
      animals. This study investigated the nature of the problems that veterinarians
      encounter in practice and assessed the potential benefit of pharmaceutical
      compounding interventions for exotic and nondomesticated fauna. The research was
      conducted at three large wildlife theme parks on the Gold Coast, Australia, using
      a multi-method design of qualitative techniques including semi-structured
      interviews accompanied by field note observations. Themes identified through the
      data analysis related to: the enthusiasm of veterinarians towards pharmaceutical
      compounding; medicated foods commonly being employed in practice; a lack of
      suitable commercially available medications; time constraint problems and
      incompatibilities between feeding and dosing intervals. A decisive factor
      identified in the uptake of compounding in veterinary care was the net cost of
      the compounding procedure when compared to the figurative "value" of the animal.
      In conlusion, the study found that pharmaceutical compounding would be able to
      deliver more effective solutions than current techniques employed for a majority
      of veterinary medication problems in the area of exotic and nondomesticated
      veterinary practice. Pharmacists therefore have opportunity to diversify their
      business model while providing an important service to the community.

PMID- 23966529
TI  - Chemical stability of amitriptyline hydrochloride in oral liquid dosage forms.
AB  - The chemical stability of amitriptyline hydrochloride in two oral liquid dosage
      forms has been studied using a stability-indicating high-performance liquid
      chromatographic assay method that was developed in our laboratory. The
      concentrations of the drug were directly related to peak heights, with an R value
      of 0.999. The percent relative standard deviation based on five injections was
      1.0. The products of decomposition and excipients present in the dosage forms did
      not interfere with the developed assay method. The formulation which contained
      edetate disodium was stable for at least 37 days when stored in amber-colored
      glass bottles at room temperature. However, the pH value of this formulation
      decreased from 5.0 to 4.0 after 37 days of storage. The formulation without
      edetate disodium was stable for only 21 days (borderline) under the same storage
      conditions. The pH value of this formulation remained constant at 5 after 37 days
      of storage at room temperature and the physical appearance of both formulations
      did not change. 

PMID- 23966530
TI  - Transdermal dosing considerations for veterinarians.
AB  - Transdermal medications are being demonstrated to be a safe and effective
      alternative to oral or parenteral dosing for certain medications. These
      medications are viable options for veterinarians and pet owners with difficult-to
      treat patients. When choosing to treat an animal with a transdermal medication,
      it is essential to consider all of the factors that affect absorption, begin with
      conservative dosing, and increase dosage slowly with proper monitoring in order
      to achieve successful therapy with a diminished risk of unwanted side effects. 

PMID- 23966531
TI  - Little thief: the domestic ferret.
AB  - Three illnesses appear commonly in pet ferrets: cardiomyopathies insulinoma, and
      adrenal associated endocrinopathy. Treatment for dilated cardiomyopathy include
      ACE inhibitors, and furosemide is recommended for the treatment for long-term
      diuresis treatment of congestive heart failure. Insulinoma, cancer of the
      pancreas, is the most common neoplasm of the American ferret, often times treated
      by surgically excising the cancerous lobes, optionally can be treated with
      steroids that suppress insulin. Adrenal disease in ferrets is due to excessive
      release of estrogen from a proliferative adrenal lesion and theoretically is
      associated with the light cycle or photoperiod to which a ferret is exposed.
      Adrenal disease is commonly treated with: environmental changes; melatonin,
      administered orally or by implant; investigative hormone implant treatments to
      decrease estrogen levels; and antihistamines to decrease episodic itching. This
      article provides the history of ferrets, clinical and medical evaluations, common
      disease states of ferrets, and discusses their role as research animals. Smaller
      animals are more challenging for veterinarians and pharmacists to treat, and the
      purpose of this article is to provide insight into those challenges. 

PMID- 23966532
TI  - Congestive heart failure and other medical facts about ferrets.
AB  - Congestive heart failure, the most common form of heart disease in aged ferrets,
      is only one of the diseases to which ferrets are susceptible. Congestive heart
      failure is an insidious, progressive disease for which there is no cure. Once the
      diagnosis is made and the proper medication is determined, the ferret must remain
      on the medication. The case report included with this article, which was
      submitted by a pet owner, and the accompanying formula is an example of how a
      compounding pharmacist can work with the veterinarian to aid in the treatment of
      a small veterinary patient by preparing specific medications. 

PMID- 23966533
TI  - Scout's Story: A Case Report on Treating Congestive Heart Failure in a Ferret.
AB  - This case study reports on a ferret diagnosted with congestive heart failure. The
      veterinarians treated it with a compounded enalapril syrup successfully.
      Radiographs of the thorax of the ferret are shown along with a photo of the
      ferret receiving her daily oral medication via oral syringe. 

PMID- 23966534
TI  - A treatment of stomatitis and treatment in cats.
AB  - A three-year old spayed female Domestic Shorthair was diagnosed with chronic
      plasmacytic stomatitis involving the mandibular gingiva caudal to the canine
      teeth. The cat presented with excessive drooling and bleeding from the gums. The
      definitive diagnosis was made on oral tissue samples obtained by biopsy and
      submitted for histopathology. The management included bilateral extraction of the
      mandibular and maxillary premolars and molars with closure of the defects
      utilizing a single mucosal flap in each quadrant. Preoperative laboratory
      evaluation and negative feline leukemia virus and/or feline immunodeficiency
      virus testing were performed. Following surgical removal of the teeth, the
      inflammation improved for eight months before returning. The cat now maintains
      comfort with parenteral injections of corticosteroid approximately every three to
      five months. Compounding pharmacists play a vital role in the treatment of
      felines due to their small size concerns with toxicity and sensitivity to certain
      medications and their reluctance to be dosed. Even in medical cases where a
      surgical procedure is the final resolution to an issue, compounded preparations
      are often required prior to surgery, during surgery, and post surgery for the
      purpose of eliminating pain and discomfort in the feline patient. 

PMID- 23966535
TI  - Azithromycin in the treatment of pneumonic foals.
AB  - Rhodococcus equi, one of the most common causes of pneumonia in foals between 3
      weeks and 5 months of age, is a troublesome disease. For many years, Rhodococcus
      equi pneumonia carried a very poor to grave prognosis due to the lack of a good
      treatment protocol. However, antibiotics that are very good at treating the
      infection have been identified. Through research we have begun to further
      understand the epidemiology of the disease, acquired an arsenal of suitabe
      treatment options, and identified prevention strategies that are actively being
      studied. Oral erythromycin requires multiple daily dosing, has inconsistent
      absorption rates in foals, and a growing number of resistant Rhodococcus equi
      isolates have been identified. Azithromycin and clarithromycin have been proposed
      as alternatives to erythromycin for the treatment of Rhodococcus equi. Studies in
      other species have demonstated that azithromycin has better pharmacokinetics and
      is safer than erythromycin. Azithromycin has shown high and sustained
      intracellular and tissue concentrations with levels still high 48 hours after
      administation of the last oral dose. Azithromycin is commercially available in
      250-mg and 500-mg tablets, and 100-mg/5 mL and 200-mg/5-mL oral suspensions. Oral
      pastes and powder feed additives in various concentrations and flavors can be
      formulated by compounding pharmacists. 

PMID- 23966536
TI  - Skin disorders in horses.
AB  - Many skin disorders in horses share the same appearance-hair loss of various
      degrees, itchiness, lesions that may or may not be painful to the touch, oozing
      sores, or skin that is reddened, crusty, scaly, flaky, thickened or swollen-
      making diagnosis sometimes difficult. A horse owner's documentation of a horse's
      medical history, the history of the skin disorder, and the horse's environment
      assists veterinarians and compounding pharmacists in their diagnosis and
      treatment. This article discusses some of the common skin problems that affect
      horses, takes a look at causes, and provides a case report of the treatment of a
      veterinary patient suffering from one of these common skin disorders. 

PMID- 23966537
TI  - Case report: tripelennamine in the treatment of skin disorders in horses.
AB  - Presented here is a case r eport on a horse that is a part of the South Dakota
      State Univeristy equestrian team. The horse experienced an itchy skin allergy, as
      did other horses. It was successfully treated with compounded tripelennamine
      hydrochloride injection and diphenhydramine hydrochloride, hydrocortisone and
      tripelennamine hydrochloride topical gel. 

PMID- 23966538
TI  - Recommended tips for treating veterinary patients.
AB  - This article contains recommended tips for treating veterinary patients. Included
      in the article is atable fo recommended flavors for common veterinary patients. 

PMID- 23966539
TI  - Saliva tests, part 2: salivary hormones, hormone replacement pharmacokinetics,
      and the importance of timely testing.
AB  - Published research has substantiated the accuracy of saliva testing in
      determining the values of specific hormones such as the major estrogens
      (estradiol, estrone, estriol), progesterone, androgens (dehydroepiandrosterone,
      testerone, 5a-dihydrotestosterone), cortisol, and melatonin. When compared with
      serum testing, saliva testing also offers multiple advantages in cost and
      convenience. In this second of a two-part series, we discuss in greater detail
      the types of hormones that can be accurately identified in saliva samples, the
      pharmacokinetics of hormone replacelment therapy,and the importance of timely
      testing. 

PMID- 23966540
TI  - Efforts to Combat Prescirption Drug Abuse-Should Not Limit Access to-Compounded
      Pain Medicines.
AB  - The practice of pharmaceutical compounding may involve the dispensing of
      controlled substances, a subset of prescription drug products. In such cases, the
      Drug Enforcement Administration has authority to regulate and enforce pharmacy
      compounding in the U.S. through the Controlled Substances Act and Drug
      Enforcement Administration regulations, although the Drug Enfocement
      Administration expressly acknowledges that the agency does not establish medical
      standards or guidelines on the treatment of pain. There is a need to balance the
      interests of law enforcement in reducing the potential for prescription drug
      abuse without adversely affecting the need to ensure appropriate availability and
      access to pain medicine. Compounding pharmacies provide an important service to
      practitioners and their patients suffering from chronic pain and debilitating
      illness. without access to pain medicine, a patient's needs would go unmet,
      resulting in unnecessary pain ad suffering. 

PMID- 23966541
TI  - An abridged history of aspirin.
AB  - The story of aspirin is a fascinating story involving war, disease, an English
      vicar, scrolls from the remote past, industrial development, corporate intrigue,
      and many other intricate and interrelated stories. This article is an abridged
      version of the history of aspirin that should tweak the interest of pharmacists
      and anyone interested in a fascinating true-life account of one of the most
      widely used medications in history. This abridged account of the history of
      aspirin represents only the surface of a fascinating story continuing its 6000
      year evolvement. 

PMID- 23966542
TI  - Designing a quality-control potency testing program for a compounding pharmacy.
AB  - Undeniably, one of the most important considerations in a compounding pharmacy's
      procedures is quality. Developing a comprehensive quality-control potency program
      must begin with the most basic activities performed at a compounding pharmacy to
      the most crucial activities. If the basics are not met, the crucial activities of
      compounding sterile and nonsterile preparations and the quality of the end
      product are in jeopardy. Basic definitions are provided in thisg article as well
      as a discussion on a three-step method on setting up a quality-control potency
      testing program, to include (1) process design and how to reduce the potential of
      variations and mistakes in compounded preparations, (2) process verification, and
      (3) how to set up a sampling plan to monitor ongoing quality. Also included are
      suggestions on how to get started on the development of a quality-control potency
      testing program. 

PMID- 23966543
TI  - Setting up a National System of Compounding Pharmacies: An Introduction.

PMID- 23966544
TI  - Gadolinium contrast media during pregnancy and lactation.

PMID- 23966545
TI  - Reply to 'Review of postoperative CT and ultrasound for endovascular aneurysm
      repair using Talent stent graft: can we simplify the surveillance protocol and
      reduce the number of CT scans?'.

PMID- 23966546
TI  - Review of postoperative CT and ultrasound for endovascular aneurysm repair using
      Talent stent graft: can we simplify the surveillance protocol and reduce the
      number of CT scans?

PMID- 23966547
TI  - Evolutionary dynamics of sex-biased genes in a hermaphrodite fungus.
AB  - Differential gene expression is believed to largely explain sexually dichotomous
      phenotypes. This phenomenon is especially significant in hermaphrodites, in which
      male and female sexual tissues have identical genotypes. Sex differences in
      transcription have been linked to molecular evolution: genes with higher
      expression in male compared with female sexual tissues (i.e., male-biased genes)
      have been associated with rapid gene divergence in various animals and plants,
      implying that selective differences exist among the sexual structures. In the
      present investigation, we examined expressed sequence tags, microarrays, and gene
      sequence data from the hermaphroditic fungus Neurospora crassa and confirmed
      selective differences of genes with disparate expression among male versus female
      sexual structures in this organism. The results held across various genotypes and
      stages of sexual development. Furthermore, our data showed that N. crassa
      comprises a rare example of an organism where female-biased genes evolve rapidly;
      they exhibited faster evolution at the protein level and reduced optimal codon
      usage compared with male-biased genes, sexually unbiased genes, and vegetative
      genes. Female-biased genes also had a greater portion of sites that experienced
      positive selection and showed stronger signals of selective sweeps than male
      biased genes, suggesting that the rapid evolution is at least partly driven by
      adaptive evolution. Distinctive aspects of the reproductive biology of N. crassa
      which might explain the rapid evolution of female-biased genes are discussed,
      particularly the propensity for female-female competition during mating, as well
      as the multifunctional nature of male structures. The present findings open new
      opportunities to test hypotheses about sex-biased gene expression and molecular
      evolution. 

PMID- 23966548
TI  - Reconstruction of ancestral 16S rRNA reveals mutation bias in the evolution of
      optimal growth temperature in the Thermotogae phylum.
AB  - Optimal growth temperature is a complex trait involving many cellular components,
      and its physiology is not yet fully understood. Evolution of continuous
      characters, such as optimal growth temperature, is often modeled as a one
      dimensional random walk, but such a model may be an oversimplification given the
      complex processes underlying the evolution of continuous characters. Recent
      articles have used ancestral sequence reconstruction to infer the optimal growth
      temperature of ancient organisms from the guanine and cytosine content of the
      stem regions of ribosomal RNA, allowing inferences about the evolution of optimal
      growth temperature. Here, we investigate the optimal growth temperature of the
      bacterial phylum Thermotogae. Ancestral sequence reconstruction using a
      nonhomogeneous model was used to reconstruct the stem guanine and cytosine
      content of 16S rRNA sequences. We compare this sequence reconstruction method
      with other ancestral character reconstruction methods, and show that sequence
      reconstruction generates smaller confidence intervals and different ancestral
      values than other reconstruction methods. Unbiased random walk simulation
      indicates that the lower temperature members of the Thermotogales have been under
      directional selection; however, when a simulation is performed that takes
      possible mutations into account, it is the high temperature lineages that are, in
      fact, under directional selection. We find that the evolution of Thermotogales
      optimal growth temperatures is best fit by a biased random walk model. These
      findings suggest that it may be easier to evolve from a high optimal growth
      temperature to a lower one than vice versa. 

PMID- 23966549
TI  - The effect of lipoaspirates cryopreservation on adipose-derived stem cells.
AB  - BACKGROUND: Autologous fat grafting has gained popularity, particularly with the
      discovery of adipose-derived stem cells (ADSC). The possibility of freezing
      lipoaspirates (LA) for later use has intriguing clinical potential. However, the
      effect of LA cryopreservation on ADSC is unclear. OBJECTIVES: The authors explore
      the effect of LA cryopreservation on ADSC viability. METHODS: Human LA (n = 8)
      were harvested using a standard technique. Lipoaspirate samples were either
      processed immediately as fresh LA (A) or stored at -20 degrees C and then at -80
      degrees C for 30 days with (B) or without (C) freezing medium. Stromal vascular
      fraction (SVF) was separated from adipocytes and either cultured to obtain
      purified ADSC or processed for the isolation of 3 distinct ADSC subpopulations
      (CD90(+)/CD45(-), CD105(+)/CD45(-), and CD34(+)/CD31(-)). Apoptosis and necrosis
      were determined by an annexin V/propidium iodide assay and quantified by flow
      cytometry. The capability of ADSC for long-term proliferation and differentiation
      was also examined. RESULTS: There were no significant differences in the
      apoptosis and necrosis of adipocytes, SVF, or ADSC between groups A and B.
      However, cell viability in SVF and ADSC was significantly compromised in group C
      as compared with group B (P < .01) due to higher ADSC apoptosis but not necrosis.
      The viable ADSC isolated from fresh or frozen LA were cultured for more than 20
      passages and demonstrated similar patterns and speed of proliferation with strong
      capability to differentiate, evidenced by cell doubling time and positive
      staining with Oil Red O (Sigma-Aldrich, St Louis, Missouri) and alkaline
      phosphatase. CONCLUSIONS: Lipoaspirates cryopreservation had a significant impact
      on ADSC apoptosis but not on ADSC necrosis, proliferation, or differentiations.
      Freezing medium provides significant protection against ADSC apoptosis.

PMID- 23966551
TI  - The Patient-Centered Medical Neighborhood: Transformation of Specialty Care.
AB  - The growing need for coordinated care of those with medically complex diseases is
      becoming more important in today's health care system, wherein reimbursement
      changes are driving methods to improve quality and cost. This article discusses
      the 6 key processes that, according to the American College of Physicians, define
      an effective medical neighborhood; the evidence supporting the need for this
      coordinated system; and pilot medical neighborhood strategies being implemented. 

PMID- 23966550
TI  - Enzymatic formation of beta-citraurin from beta-cryptoxanthin and Zeaxanthin by
      carotenoid cleavage dioxygenase4 in the flavedo of citrus fruit.
AB  - In this study, the pathway of beta-citraurin biosynthesis, carotenoid contents
      and the expression of genes related to carotenoid metabolism were investigated in
      two varieties of Satsuma mandarin (Citrus unshiu), Yamashitabeni-wase, which
      accumulates beta-citraurin predominantly, and Miyagawa-wase, which does not
      accumulate beta-citraurin. The results suggested that CitCCD4 (for Carotenoid
      Cleavage Dioxygenase4) was a key gene contributing to the biosynthesis of beta
      citraurin. In the flavedo of Yamashitabeni-wase, the expression of CitCCD4
      increased rapidly from September, which was consistent with the accumulation of
      beta-citraurin. In the flavedo of Miyagawa-wase, the expression of CitCCD4
      remained at an extremely low level during the ripening process, which was
      consistent with the absence of beta-citraurin. Functional analysis showed that
      the CitCCD4 enzyme exhibited substrate specificity. It cleaved beta-cryptoxanthin
      and zeaxanthin at the 7,8 or 7',8' position. But other carotenoids tested in this
      study (lycopene, alpha-carotene, beta-carotene, all-trans-violaxanthin, and 9-cis
      violaxanthin) were not cleaved by the CitCCD4 enzyme. The cleavage of beta
      cryptoxanthin and zeaxanthin by CitCCD4 led to the formation of beta-citraurin.
      Additionally, with ethylene and red light-emitting diode light treatments, the
      gene expression of CitCCD4 was up-regulated in the flavedo of Yamashitabeni-wase.
      These increases in the expression of CitCCD4 were consistent with the
      accumulation of beta-citraurin in the two treatments. These results might provide
      new strategies to improve the carotenoid contents and compositions of citrus
      fruits. 

PMID- 23966552
TI  - Assessment of the phenotype and functionality of porcine CD8 T cell responses
      following vaccination with live attenuated classical swine fever virus (CSFV) and
      virulent CSFV challenge.
AB  - Vaccination with live attenuated classical swine fever virus (CSFV) induces solid
      protection after only 5 days, which has been associated with virus-specific T
      cell gamma interferon (IFN-gamma) responses. In this study, we employed flow
      cytometry to characterize T cell responses following vaccination and subsequent
      challenge infections with virulent CSFV. The CD3(+) CD4(-) CD8(hi) T cell
      population was the first and major source of CSFV-specific IFN-gamma. A
      proportion of these cells showed evidence for cytotoxicity, as evidenced by
      CD107a mobilization, and coexpressed tumor necrosis factor alpha (TNF-alpha). To
      assess the durability and recall of these responses, a second experiment was
      conducted where vaccinated animals were challenged with virulent CSFV after 5
      days and again after a further 28 days. While virus-specific CD4 T cell (CD3(+)
      CD4(+) CD8alpha(+)) responses were detected, the dominant response was again from
      the CD8 T cell population, with the highest numbers of these cells being detected
      14 and 7 days after the primary and secondary challenges, respectively. These CD8
      T cells were further characterized as CD44(hi) CD62L(-) and expressed variable
      levels of CD25 and CD27, indicative of a mixed effector and effector memory
      phenotype. The majority of virus-specific IFN-gamma(+) CD8 T cells isolated at
      the peaks of the response after each challenge displayed CD107a on their surface,
      and subpopulations that coexpressed TNF-alpha and interleukin 2 (IL-2) were
      identified. While it is hoped that these data will aid the rational design and/or
      evaluation of next-generation marker CSFV vaccines, the novel flow cytometric
      panels developed should also be of value in the study of porcine T cell responses
      to other pathogens/vaccines. 

PMID- 23966553
TI  - Haplotypes of the IL10 gene as potential protection factors in leprosy patients.
AB  - Leprosy is an infectious disease caused by Mycobacterium leprae characterized by
      dermatoneurological signs and symptoms that has a large number of new cases
      worldwide. Several studies have associated interleukin 10 with
      susceptibility/resistance to several diseases. We investigated haplotypes formed
      by three single nucleotide polymorphisms (SNPs) located in the IL10 gene (A
      1082G, C-819T, and C-592A) in order to better understand the susceptibility to
      and severity of leprosy in an admixed northern Brazil population, taking into
      account estimates of interethnic admixture. We observed the genotypes ACC/ACC (P
      = 0.021, odds ratio [OR] [95% confidence interval (CI)] = 0.290 [0.085 to 0823])
      and ACC/GCC (P = 0.003, OR [95% CI] = 0.220 [0.504 to 0.040]) presenting
      significant results for protection against leprosy development, framed in the
      profiles of low and medium interleukin production, respectively. Therefore, we
      suggest that genotypes A-1082G, C-819T, and C-592A formed by interleukin-10
      polymorphisms are closely related to protection of the leprosy development in an
      admixed northern Brazil population, in particular ACC/ACC and ACC/GCC genotypes. 

PMID- 23966554
TI  - Identification of a highly antigenic region of subtilisin-like serine protease 1
      for serodiagnosis of Neospora caninum infection.
AB  - Neospora caninum is an apicomplexan parasite that causes abortion in cattle;
      hence, accurate diagnosis of this pathogen is important to the cattle farming
      industry. Our previous proteomics and immunoscreening analyses revealed that the
      N. caninum subtilisin-like serine protease 1 (NcSUB1) has potential as a
      serodiagnostic tool for Neospora. Consequently, we expressed two fragments
      containing five NcSUB1 tandem repeat copies covering amino acids (aa) 524 to 843
      (NcSUB1t) and 555 to 679 (NcSUB1tr) to identify the antigenic regions. The
      serodiagnostic performances of NcSUB1t and NcSUB1tr were compared with that of
      N54, which contains a single copy of the repeats (aa 649 to 784), and with the
      truncated NcSAG1 (NcSAG1t), which lacks a signal peptide and C-terminal
      hydrophobic regions, as a positive reference. Serum samples from N. caninum
      experimentally infected cattle and mice and cattle from a farm with confirmed
      cases of Neospora abortion were tested by enzyme-linked immunosorbent assay
      (ELISA) with the four antigens. In the N. caninum experimentally infected cattle,
      the highest IgG1 antibody titers were detected against NcSUB1t, while specific
      IgG1 antibodies were detectable from 16 days postinfection (dpi), with levels
      peaking at 36 dpi for all of the antigens. On the other hand, the levels of anti
      NcSUB1 IgG2 antibodies were lower than those of anti-SAG1t IgG2 antibodies. The
      ELISA with NcSUB1t and NcSUB1tr had good sensitivity (94.59 to 95.95%) and
      specificity (80 to 100%) with bovine serum field samples compared to NcSAG1t and
      showed no cross-reactions with sera from Toxoplasma gondii experimentally
      infected mice. Moreover, IgG antibodies against NcSUB1t were detected during
      parturition in the NcSAG1t antibody-positive cattle, and NcSUB1t-specific
      antibody transfer was observed from a mother to her calf. Our results show that
      the NcSUB1 tandem repeat is potentially useful for serodiagnosis of N. caninum. 

PMID- 23966555
TI  - Insight from molecular, pathological, and immunohistochemical studies on cellular
      and humoral mechanisms responsible for vaccine-induced protection of rainbow
      trout against Yersinia ruckeri.
AB  - The immunological mechanisms associated with protection of vaccinated rainbow
      trout, Oncorhynchus mykiss, against enteric redmouth disease (ERM), caused by
      Yersinia ruckeri, were previously elucidated by the use of gene expression
      methodology and immunochemical methods. That approach pointed indirectly to both
      humoral and cellular elements being involved in protection. The present study
      correlates the level of protection in rainbow trout to cellular reactions in
      spleen and head kidney and visualizes the processes by applying
      histopathological, immunohistochemical, and in situ hybridization techniques. It
      was shown that these cellular reactions, which were more prominent in spleen than
      in head kidney, were associated with the expression of immune-related genes,
      suggesting a Th2-like response. Y. ruckeri, as shown by in situ hybridization
      (ISH), was eliminated within a few days in vaccinated fish, whereas nonprotected
      fish still harbored bacteria for a week after infection. Vaccinated fish
      reestablished normal organ structure within a few days, whereas nonprotected fish
      showed abnormalities up to 1 month postinfection. Protection in the early phase
      of infection was mainly associated with the expression of genes encoding innate
      factors (complement factors, lysozyme, and acute phase proteins), but in the
      later phase of infection, increased expression of adaptive immune genes
      dominated. The histological approach used has shown that the cellular changes
      correlated with protection of vaccinated fish. They comprised transformation of
      resident cells into macrophage-like cells and increased occurrence of CD8alpha
      and IgM cells, suggesting these cells as main players in protection. Future
      studies should investigate the causality between these factors and protection. 

PMID- 23966556
TI  - Randomized, controlled, multicenter study of the immunogenicity and safety of a
      fully liquid combination diphtheria-tetanus toxoid-five-component acellular
      pertussis (DTaP5), inactivated poliovirus (IPV), and haemophilus influenzae type
      b (Hib) vaccine compared with a DTaP3-IPV/Hib vaccine administered at 3, 5, and
      12 months of age.
AB  - This study compared the levels of immunogenicity and safety of diphtheria-tetanus
      toxoid-five-component acellular pertussis (DTaP(5)), inactivated poliovirus
      (IPV), and Haemophilus influenzae type b (Hib) (DTaP(5)-IPV-Hib) and DTaP(3)
      IPV/Hib vaccines for study participants 3, 5, and 12 months of age. Post-dose 3
      noninferiority criteria comparing DTaP(5)-IPV-Hib to DTaP(3)-IPV/Hib using rates
      of seroprotection were demonstrated against diphtheria, tetanus, and polio types
      1 to 3, but not for polyribosylribitol phosphate (PRP). While PRP did not meet
      noninferiority criteria, the seroprotection rate and geometric mean concentration
      (GMC) were high, indicating a clinically robust immune response. GMCs or titers
      for other antigens (including pertussis) and the safety profiles were generally
      similar between groups. Fully liquid DTaP(5)-IPV-Hib can be administered using
      the 3-, 5-, and 12-month vaccination schedule. (This study has been registered at
      ClinicalTrials.gov under registration no. NCT00287092.).

PMID- 23966557
TI  - All-trans-retinoic acid imprints expression of the gut-homing marker alpha4beta7
      while suppressing lymph node homing of dendritic cells.
AB  - Tissue-directed trafficking of dendritic cells (DCs) as natural adjuvants and/or
      direct vaccine carriers is highly attractive for the next generation of vaccines
      and immunotherapeutics. Since these types of studies would undoubtedly be first
      conducted using nonhuman primate models, we evaluated the ability of all-trans
      retinoic acid (ATRA) to induce gut-homing alpha4beta7 expression on rhesus
      macaque plasmacytoid and myeloid DCs (pDCs and mDCs, respectively). Induction of
      alpha4beta7 occurred in both a time-dependent and a dose-dependent manner with up
      to 8-fold increases for mDCs and 2-fold increases for pDCs compared to medium
      controls. ATRA treatment was also specific in inducing alpha4beta7 expression,
      but not expression of another mucosal trafficking receptor, CCR9. Unexpectedly,
      upregulation of alpha4beta7 was associated with a concomitant downregulation of
      CD62L, a marker of lymph node homing, indicating an overall shift in the
      trafficking repertoire. These same phenomena occurred with ATRA treatment of
      human and chimpanzee DCs, suggesting a conserved mechanism among primates.
      Collectively, these data serve as a first evaluation for ex vivo modification of
      primate DC homing patterns that could later be used in reinfusion studies for the
      purposes of immunotherapeutics or mucosa-directed vaccines. 

PMID- 23966558
TI  - Diarrhea in early childhood: short-term association with weight and long-term
      association with length.
AB  - The short-term association between diarrhea and weight is well-accepted, but the
      long-term association between diarrhea and growth is less clear. Using data from
      7 cohort studies (Peru, 1985-1987; Peru, 1989-1991; Peru, 1995-1998; Brazil, 1989
      1998; Guinea-Bissau, 1987-1990; Guinea-Bissau, 1996-1997; and Bangladesh, 1993
      1996), we evaluated the lagged relationship between diarrhea and growth in the
      first 2 years of life. Our analysis included 1,007 children with 597,638 child
      days of diarrhea surveillance and 15,629 anthropometric measurements. We
      calculated the associations between varying diarrhea burdens during lagged 30-day
      periods and length at 24 months of age. The cumulative association between the
      average diarrhea burden and length at age 24 months was -0.38 cm (95% confidence
      interval: -0.59, -0.17). Diarrhea during the 30 days prior to anthropometric
      measurement was consistently associated with lower weight at most ages, but there
      was little indication of a short-term association with length. Diarrhea was
      associated with a small but measurable decrease in linear growth over the long
      term. These findings support a focus on prevention of diarrhea as part of an
      overall public health strategy for improving child health and nutrition; however,
      more research is needed to explore catch-up growth and potential confounders. 

PMID- 23966560
TI  - Customized versus population-based birth weight charts for the detection of
      neonatal growth and perinatal morbidity in a cross-sectional study of term
      neonates.
AB  - Customized birth weight charts that incorporate maternal characteristics are now
      being adopted into clinical practice. However, there is controversy surrounding
      the value of these charts in the prediction of growth and perinatal outcomes. The
      objective of this study was to assess the use of customized charts in predicting
      growth, defined by body fat percentage, and perinatal morbidity. A total of 581
      term (>=37 weeks' gestation) neonates born in Sydney, Australia, in 2010 were
      included. Body fat percentage measurements were taken by using air displacement
      plethysmography. Objective composite measurements of perinatal morbidity were
      used to identify neonates who had poor outcomes; these data were extracted from
      medical records. The value of customized charts was assessed by calculating
      positive predictive values, negative predictive values, and odds ratios with 95%
      confidence intervals. Customized versus population-based charts did not improve
      the prediction of either low body fat percentage (59% vs. 66% positive predictive
      value and 87% vs. 89% negative predictive value, respectively) or high body fat
      percentage (48% vs. 53% positive predictive value and 90% vs. 89% negative
      predictive value, respectively). Customized charts were not better than
      population-based charts at predicting perinatal morbidity (for customized charts,
      odds ratio = 1.02, 95% confidence interval: 1.01, 1.04; for population-based
      charts, odds ratio = 1.03, 95% confidence interval: 1.01, 1.05) per percentile
      decrease in birth weight. Customized birth weight charts do not provide
      significant improvements over population-based charts in predicting neonatal
      growth and morbidity. 

PMID- 23966559
TI  - A prospective study of circulating C-reactive protein, interleukin-6, and tumor
      necrosis factor alpha receptor 2 levels and risk of ovarian cancer.
AB  - Chronic inflammation may play a role in ovarian carcinogenesis. We examined
      associations between 3 plasma biomarkers of inflammation-C-reactive protein
      (CRP), interleukin 6, and tumor necrosis factor alpha receptor 2-and risk of
      invasive epithelial ovarian cancer in prospectively collected samples from the
      Nurses' Health Study (NHS; 1989-2010), Nurses' Health Study II (NHS II; 1996
      2009), and the Women's Health Study (WHS; 1992-2011) and performed a meta
      analysis including data from previous publications. Associations with ovarian
      cancer risk were calculated using logistic regression (NHS/NHS II; n = 217 cases)
      or Cox proportional hazards regression (WHS; n = 159 cases). Study-specific
      results were combined using random-effects meta-analysis. In the NHS/NHS II and
      WHS, we observed a 53% increased risk of invasive ovarian cancer when comparing
      women in the fourth quartile of CRP with women in the first quartile (95%
      confidence interval (CI): 1.05, 2.23). A CRP level of >10 mg/L versus a level of
      <=1 mg/L was associated with a 2.16-fold increased risk (95% CI: 1.23, 3.78). In
      a meta-analysis of published studies, women in the third tertile of CRP had a 35%
      increased risk (95% CI: 1.10, 1.67) compared with women in the first tertile.
      There were no significant associations between interleukin 6 or tumor necrosis
      factor alpha receptor 2 and risk in the NHS/NHS II. Our results support the
      hypothesis that higher levels of circulating CRP are associated with increased
      risk of ovarian cancer, indicating that the role of inflammation in ovarian
      cancer requires further elucidation. 

PMID- 23966561
TI  - Invited commentary: the incremental value of customization in defining abnormal
      fetal growth status.
AB  - Reference tools based on birth weight percentiles at a given gestational week
      have long been used to define fetuses or infants that are small or large for
      their gestational ages. However, important deficiencies of the birth weight
      reference are being increasingly recognized. Overwhelming evidence indicates that
      an ultrasonography-based fetal weight reference should be used to classify fetal
      and newborn sizes during pregnancy and at birth, respectively. Questions have
      been raised as to whether further adjustments for race/ethnicity, parity, sex,
      and maternal height and weight are helpful to improve the accuracy of the
      classification. In this issue of the Journal, Carberry et al. (Am J Epidemiol.
      2013;178(8):1301-1308) show that adjustment for race/ethnicity is useful, but
      that additional fine tuning for other factors (i.e., full customization) in the
      classification may not further improve the ability to predict infant morbidity,
      mortality, and other fetal growth indicators. Thus, the theoretical advantage of
      full customization may have limited incremental value for pediatric outcomes,
      particularly in term births. Literature on the prediction of short-term maternal
      outcomes and very long-term outcomes (adult diseases) is too scarce to draw any
      conclusions. Given that each additional variable being incorporated in the
      classification scheme increases complexity and costs in practice, the clinical
      utility of full customization in obstetric practice requires further testing. 

PMID- 23966563
TI  - Point: cervical cancer screening guidelines should consider observational data on
      screening efficacy in older women.
AB  - Recent guidelines from the American Cancer Society, the American Society for
      Colposcopy and Cervical Pathology, and the American Society for Clinical
      Pathology recommend cessation of cervical cancer screening at age 65 years for
      women with an "adequate" history of negative Papanicolaou smears. In our view,
      those who formulated these guidelines did not consider a growing body of evidence
      from nonrandomized studies that provides insight into the efficacy of cervical
      cancer screening among older women. First, older women are not at indefinitely
      low risk following negative screening results. Second, recent data from the
      United States, the United Kingdom, and Sweden suggest that screening of older
      women is associated with substantial reductions in cervical cancer incidence and
      mortality, even among previously screened women. It may be that after
      consideration of the reduced incidence of (and reduced mortality from) cervical
      cancer that may result from screening older women, the harms and economic costs
      of screening will be judged to outweigh its benefits. However, it is essential to
      consider the now-documented benefits of cervical screening when formulating
      screening guidelines for older women, and recommendations that do not do so will
      lack an evidence base. 

PMID- 23966564
TI  - Counterpoint: cervical cancer screening guidelines--approaching the golden age.
AB  - Changes in screening guidelines that imply suppression of procedures once
      recommended are always controversial because of the perception that benefits are
      being curtailed. Prior to 2012, cervical cancer screening guidelines issued by US
      based expert bodies differed in several decision areas, making clinicians
      essentially cherry-pick among recommendations. To some extent, this approach to
      screening practices also served to shield clinicians from litigation. It implied
      starting screening earlier, doing it more frequently, and stopping later in life
      than necessary. This state of affairs changed in 2012, when the most influential
      professional groups updated their cervical screening guidelines, and
      recommendations became essentially unified. All groups recommended that women
      older than 65 years of age discontinue cervical cancer screening on the basis of
      evidence that screening benefits in this age group were minor and far outweighed
      by harms. The guidelines are very specific about the exceptions, which ensure
      acceptable safety. It is expected that the new guidelines will permit less
      wasteful cervical screening, while fostering the opportunity to direct resources
      towards ensuring adequate coverage of high-risk women. 

PMID- 23966565
TI  - Assembler for de novo assembly of large genomes.
AB  - Assembling a large genome using next generation sequencing reads requires large
      computer memory and a long execution time. To reduce these requirements, we
      propose an extension-based assembler, called JR-Assembler, where J and R stand
      for "jumping" extension and read "remapping." First, it uses the read count to
      select good quality reads as seeds. Second, it extends each seed by a whole-read
      extension process, which expedites the extension process and can jump over short
      repeats. Third, it uses a dynamic back trimming process to avoid extension
      termination due to sequencing errors. Fourth, it remaps reads to each assembled
      sequence, and if an assembly error occurs by the presence of a repeat, it breaks
      the contig at the repeat boundaries. Fifth, it applies a less stringent extension
      criterion to connect low-coverage regions. Finally, it merges contigs by unused
      reads. An extensive comparison of JR-Assembler with current assemblers using
      datasets from small, medium, and large genomes shows that JR-Assembler achieves a
      better or comparable overall assembly quality and requires lower memory use and
      less central processing unit time, especially for large genomes. Finally, a
      simulation study shows that JR-Assembler achieves a superior performance on
      memory use and central processing unit time than most current assemblers when the
      read length is 150 bp or longer, indicating that the advantages of JR-Assembler
      over current assemblers will increase as the read length increases with advances
      in next generation sequencing technology. 

PMID- 23966566
TI  - Induced plant defenses, host-pathogen interactions, and forest insect outbreaks.
AB  - Cyclic outbreaks of defoliating insects devastate forests, but their causes are
      poorly understood. Outbreak cycles are often assumed to be driven by density
      dependent mortality due to natural enemies, because pathogens and predators cause
      high mortality and because natural-enemy models reproduce fluctuations in
      defoliation data. The role of induced defenses is in contrast often dismissed,
      because toxic effects of defenses are often weak and because induced-defense
      models explain defoliation data no better than natural-enemy models. Natural
      enemy models, however, fail to explain gypsy moth outbreaks in North America, in
      which outbreaks in forests with a higher percentage of oaks have alternated
      between severe and mild, whereas outbreaks in forests with a lower percentage of
      oaks have been uniformly moderate. Here we show that this pattern can be
      explained by an interaction between induced defenses and a natural enemy. We
      experimentally induced hydrolyzable-tannin defenses in red oak, to show that
      induction reduces variability in a gypsy moth's risk of baculovirus infection.
      Because this effect can modulate outbreak severity and because oaks are the only
      genus of gypsy moth host tree that can be induced, we extended a natural-enemy
      model to allow for spatial variability in inducibility. Our model shows
      alternating outbreaks in forests with a high frequency of oaks, and uniform
      outbreaks in forests with a low frequency of oaks, matching the data. The
      complexity of this effect suggests that detecting effects of induced defenses on
      defoliator cycles requires a combination of experiments and models. 

PMID- 23966567
TI  - Two ScFv antibody libraries derived from identical VL-VH framework with different
      binding site designs display distinct binding profiles.
AB  - In directed evolution experiments, a single randomization scheme of an antibody
      gene does not provide optimal diversity for recognition of all sizes of antigens.
      In this study, we have expanded the recognition potential of our universal
      library, termed ScFvP, with a second distinct diversification scheme. In the
      second library, termed ScFvM, diversity was designed closer to the center of the
      antigen binding site in the same antibody framework as earlier. Also, the CDR-H3
      loop structures were redesigned to be shorter, 5-12 aa and mostly without the
      canonical salt bridge between Arg106H and Asp116H to increase the flexibility of
      the loop and to allow more space in the center of the paratope for binding
      smaller targets. Antibodies were selected from the two libraries against various
      antigens separately and as a mixture. The origin and characteristics of the
      retrieved antibodies indicate that complementary diversity results in
      complementary functionality widening the spectrum of targets amenable for
      selection.

PMID- 23966568
TI  - Is prophylactic surgery for femoroacetabular impingement indicated? A systematic
      review.
AB  - BACKGROUND: This is a systematic review to determine if prophylactic surgical
      intervention for asymptomatic patients with radiographic evidence of
      femoroacetabular impingement (FAI) is warranted to prevent early degenerative
      joint disease of the hip. METHODS: A systematic search was performed from 1965 to
      2013 in PubMed and EMBASE. Inclusion criteria were prospective or retrospective
      studies comparing skeletally mature asymptomatic patients with radiographic
      evidence of FAI treated with prophylactic hip arthroscopic surgery versus
      nonoperative management. A total of 840 references were identified from the
      searches. After detailed eligibility screening, none of the references met the
      eligibility criteria. RESULTS: No trials were identified that met the criteria
      for inclusion in the review. CONCLUSION: There is a lack of available evidence to
      support surgical intervention for the treatment of FAI in asymptomatic patients.
      This article attempts to address this dilemma by reviewing the available
      literature to answer several questions that would indirectly address the topic.
      First, what is the prevalence of FAI in the asymptomatic population? Second, what
      is the natural history of FAI if left untreated? Upon reviewing these issues, the
      authors' conclusion parallels that of the systematic review: Current evidence
      does not support prophylactic surgery for asymptomatic FAI in the vast majority
      of cases. However, limited evidence suggests that asymptomatic patients who have
      previously undergone total hip arthroplasty for FAI-induced osteoarthritis of the
      contralateral hip are at a significantly increased risk for early degenerative
      joint disease. Further research is needed to better clarify surgical indications.

PMID- 23966569
TI  - Antiplatelet treatment in the secondary prevention of coronary and
      cerebrovascular disease: is there any place for novel agents?
AB  - Ischemic heart disease and cerebrovascular disease remain major health problems
      with associated mortality and quality-of-life consequences. Antiplatelet agents,
      including thienopyridines and the new P2Y12 inhibitors, have been shown to
      improve survival in the secondary prevention setting. We review the available
      evidence on the effectiveness and safety of previous established as well as novel
      antithrombotic agents in the secondary prevention of cardiovascular disease with
      a special focus on cerebrovascular disease.

PMID- 23966570
TI  - Impact of Diabetes Mellitus on Critical Limb Ischemia With Below the Knee
      Disease: Japan Below-the-Knee Artery Treatment Subanalysis.
AB  - Background:A strong association exists between diabetes mellitus and critical
      limb ischemia.Methods and Results:We performed endovascular therapy on 1060 limbs
      in 884 patients with below knee lesions only. The patients were divided into
      diabetes (DG) and nondiabetes groups (NDG). Limb salvage was poorer in the DG
      (79% vs 89%, P = .0061). No significant difference was observed in mortality,
      amputation-free survival (AFS), and target vessel revascularization (TVR).
      Multivariate analysis revealed diabetes status, infection, poor activity of daily
      living (ADL), younger age, and procedure failure as independent predictors of
      major amputation in DG. In the NDG, procedure failure was the predictor, and
      younger age and poor ADL showed tendency of major
      amputation.Conclusions:Mortality, AFS, and TVR showed no significant difference
      between the 2 groups, but major amputation was more frequent in DG. Not only
      revascularization but also infection and diabetes control were very important for
      limb salvage in DG.

PMID- 23966571
TI  - Peripheral artery disease is an independent predictor of mortality after
      implantable cardioverter-defibrillator implantation in patients with severe left
      ventricular dysfunction.
AB  - The impact of peripheral artery disease (PAD) on survival in implantable
      cardioverter defibrillator (ICD) patients is poorly understood. Thus, we assessed
      the risk of PAD in our adult ICD patients with left ventricular dysfunction
      (ejection fraction [EF] <=35%). Survival was estimated with Kaplan-Meier method
      and compared by the log-rank test; a Cox proportional hazards model assessed the
      effects of clinical variables on survival. Average age and EF of 1399 patients
      were 67.0 +/- 12.1 years and 23.8% +/- 7.2%, respectively. The ICD patients with
      PAD had significantly worse survival than those without (unadjusted P < .0001).
      The multivariate predictors of survival at implant were (hazard ratio, HR [95%
      confidence interval]) age (HR 1.05 [1.04-1.07] P < .0001), PAD (HR 2.07 [1.53
      2.80] P < .0001), class III/IV heart failure (HR 1.36 [1.06-1.76] P = .016),
      creatinine 1.4-2.0 mg/dL (HR 1.36 [1.05-1.76] P = .019), and creatinine >=2.0
      mg/dL (HR 2.01 [1.42-2.85] P < .0001). The PAD is an independent predictor of
      mortality and should be considered in the preimplant risk assessment.

PMID- 23966572
TI  - Association between uric acid and coronary collateral circulation in patients
      with stable coronary artery disease.
AB  - Serum uric acid (SUA) levels have been proposed as a biomarker of coronary artery
      disease (CAD) and coronary collateral circulation (CCC). We investigated the
      association between SUA levels and development of CCC in patients with stable
      CAD. Consecutive patients (n = 480) with stable CAD who underwent coronary
      angiography and documented total occlusion in 1 of the major coronary arteries
      were included in this study. Levels of fasting blood glucose, white blood cell
      (WBC), creatinine, platelet count, and SUA were significantly higher in patients
      with poor CCC than in those with good CCC. After multivariate analysis, high
      levels of SUA were an independent predictor of CCC together with levels of
      fasting blood glucose and WBC. The receiver-operating characteristic analysis
      provided a cutoff value of 5.65 mg/dL for SUA to predict poor CCC with 60%
      sensitivity and 66% specificity. High levels of SUA may be associated with poor
      CCC in patients with stable CAD. 

PMID- 23966573
TI  - Lithium carbonate decreases acute suicidality in posttraumatic stress disorder.

PMID- 23966574
TI  - Can an accessory renal artery be safely covered during endovascular aortic
      aneurysm repair?
AB  - A best evidence topic was constructed according to a structured protocol. The
      question addressed was whether coverage of an accessory renal artery (ARA) in
      patients undergoing endovascular aortic aneurysm repair (EVAR) is associated with
      increased risk of renal impairment. Altogether, 106 papers were located using the
      reported searches, of which 5 represented the best evidence to answer the
      question. The authors, journal, date and country of publication, study type,
      patient group studied, relevant outcomes parameters and results of these papers
      are tabulated. Our best evidence analysis included 116 patients who had one or
      more ARA excluded during EVAR. Segmental renal infarction occurred in varying
      numbers of patients (ranging from 0 to 84%). The authors consistently demonstrate
      that loss of renal mass is not associated with functional renal impairment,
      expressed by various outcome parameters such as serum creatinine, glomerular
      filtration rate (GFR), renal failure requiring dialysis and worsening
      hypertension. Comparisons of groups of patient with covered or preserved ARAs by
      one of the selected studies showed no difference in any of these renal outcome
      parameters, apart from a significantly higher renal infarct volume in the former
      group (P < 0.001). Subgroup analysis of patients with pre-existing renal
      dysfunction (GFR < 60 ml/h/m(2)) showed no difference in GFR change when
      comparing covered with uncovered ARA patient cohorts. No type II endoleak related
      to the covered ARA was reported in any of these studies. In conclusion, current
      evidence supports the safety of coverage of ARAs located in the proximal fixation
      zone to achieve seal in EVAR. 

PMID- 23966575
TI  - Successful stent for a pseudoaneurysm after the patent ductus arteriosus closure
      procedure.
AB  - We describe the case of a large pseudoaneurysm after transcatheter closure of
      patent ductus arteriosus in a 42-year old male who developed back pain and
      dyspnoea 6 months subsequent to the first procedure. The patient's pseudoaneurysm
      was successfully treated using Talent prostheses (Medtronic AVE, Santa Rosa, CA,
      USA), though the postoperative course was without incident. 

PMID- 23966576
TI  - Does tranexamic acid stop haemoptysis?
AB  - A best evidence topic in thoracic surgery was written according to a structured
      protocol. The question addressed was 'Does tranexamic acid stop haemoptysis'?
      Altogether 49 papers were found using the reported search strategy, of which 13
      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. This consisted of
      one systematic review including a meta-analysis of two double-blind randomized
      controlled trials (RCTs), the two RCTs, one cohort study, two case-series and
      seven case reports. Main outcomes included bleeding time, bleeding volume and
      occurrence of thromboembolic complications after start of treatment. Based on
      results from the meta-analysis, no difference in remission of bleeding within 1
      week was found between tranexamic acid (TA) and placebo groups (odds ratio 1.56,
      95% CI: 0.44-5.46). However, overall bleeding time was significantly shorter for
      the TA group (weighted mean difference -19.47, 95% CI: -26.90, -12.03 h). In one
      RCT, TA reduced both the duration and the volume of bleeding compared with
      patients receiving placebo (both P < 0.0005). However, the other RCT failed to
      find a difference in bleeding time (P = 0.2). In these studies, no patient
      suffered from thromboembolic complications. Two case reports, however, describe
      development of pulmonary embolism during TA treatment. Several case reports on
      the use of TA for treatment of haemoptysis secondary to cystic fibrosis were
      found. In general, they suggest that TA may be a useful and well-tolerated
      medication for the treatment of intractable haemoptysis in this patient group. We
      conclude that limited research on the use of TA for treatment of haemoptysis
      exists. As aetiology of haemoptysis as well as length of treatment, dosage and
      form of TA administration varied between the studies, strong recommendations are
      difficult to give. Current best evidence, however, indicates that TA may reduce
      both the duration and volume of bleeding, with low risk of short-term
      thromboembolic complications, in patients with haemoptysis. 

PMID- 23966577
TI  - The use of metformin and colorectal cancer incidence in patients with type II
      diabetes mellitus.
AB  - BACKGROUND: Experimental studies have suggested that metformin may decrease the
      incidence of colorectal cancer in patients with type II diabetes. However,
      previous observational studies have reported contradictory results, which are
      likely due to important methodologic limitations. Thus, the objective of this
      study was to assess whether the use of metformin is associated with the incidence
      of colorectal cancer in patients with type II diabetes. METHODS: A cohort study
      of patients newly treated with non-insulin antidiabetic agents was assembled
      using the United Kingdom Clinical Practice Research Datalink. A nested case
      control analysis was conducted, where all incident cases of colorectal cancer
      occurring during follow-up were identified and randomly matched with up to 10
      controls. Conditional logistic regression was used to estimate adjusted rate
      ratios (RR) of colorectal cancer associated with ever use, and cumulative
      duration of use of metformin. All models accounted for latency and were adjusted
      for relevant potential confounding factors. RESULTS: Overall, ever use of
      metformin was not associated with the incidence of colorectal cancer [RR: 0.93;
      95% confidence interval (CI), 0.73-1.18]. Similarly, no dose-response
      relationship was observed in terms of cumulative duration of use. CONCLUSIONS:
      The use of metformin was not associated with the incidence of colorectal cancer
      in patients with type II diabetes. IMPACT: The results of this study do not
      support the launch of metformin randomized controlled trials for the
      chemoprevention of colorectal cancer.

PMID- 23966578
TI  - Family history of diabetes and pancreatic cancer as risk factors for pancreatic
      cancer: the PACIFIC study.
AB  - Genetic association studies have identified more than a dozen genes associated
      with risk of pancreatic cancer. Given this genetic heterogeneity, family history
      can be useful for identifying individuals at high risk for this disease. The goal
      of this analysis was to evaluate associations of family history of diabetes and
      family history of pancreatic cancer with risk of pancreatic cancer. PACIFIC is a
      case-control study based on two large health plans. Cases were diagnosed with
      pancreatic ductal adenocarcinoma (PDA) and controls were selected from the health
      plan enrollment databases and frequency matched to cases. Family history data
      were collected using an interviewer-administered questionnaire and were available
      on 654 cases and 697 controls. Logistic regression was used for the association
      analyses. First-degree relative history of diabetes was statistically
      significantly associated with increased risk of PDA [OR, 1.37; 95% confidence
      interval (CI), 1.10-1.71]. The highest risk of PDA was observed for an offspring
      with diabetes (OR, 1.95; 95% CI, 1.23-3.09). In addition, history of pancreatic
      cancer increased risk for PDA with an OR of 2.79 (95% CI, 1.44-4.08) for any
      first-degree relative history of pancreatic cancer. This population-based
      analysis showed that family history of diabetes was associated with increased
      risk of PDA and confirmed previous studies showing that first-degree family
      history of pancreatic cancer is associated with PDA. These results support the
      need for ongoing studies of genetic influences on pancreatic cancer in large
      samples and investigations of possible pleiotropic genetic effects on diabetes
      and pancreatic cancer.

PMID- 23966579
TI  - Increased proliferative background in healthy women with BRCA1/2
      haploinsufficiency is associated with high risk for breast cancer.
AB  - Previous studies indicated that BRCA haploinsufficiency was associated with
      activation of the EGF receptor (EGFR) signaling pathway and increased
      proliferative activity in mammary epithelial cells of healthy women. We
      hypothesized that these processes might be reflected in the expression of
      serologic soluble EGFR (sEGFR) and thymidine kinase 1 (TK1) activity, which
      signal the initial and final steps of the proliferative pathway, respectively. We
      found that healthy carriers of BRCA1/2 mutations (n = 80) showed a significantly
      higher TK1 activity than age-matched controls (P = 0.0003), and TK1 activity was
      similar in women with BRCA1 and BRCA2 mutations (P = 0.74). The sEGFR
      concentration was significantly higher in women with BRCA1 than in controls and
      BRCA2 mutation (P = 0.013 and 0.002, respectively). During follow-up, four of 80
      BRCA1/2 mutation carriers developed breast cancer. These women showed a
      significantly higher TK1 activity and somewhat higher sEGFR concentrations than
      the other 76 BRCA1/2 carriers (P = 0.04 and 0.09, respectively). All tumors were
      negative for ovarian hormone receptors, but showed a high EGFR expression. This
      study was limited by the short-term follow-up (mean, 27 months; range, 5-45),
      which resulted in a small sample size. Women with BRCA1 and BRCA2 mutations that
      had undergone risk-reducing bilateral salpingo-oophorectomy (BSO) showed
      significantly lower sEGFR compared with those without surgery (P = 0.007 and
      0.038, respectively). Larger, prospective studies are warranted to investigate
      whether TK1 and sEGFR measurements may be useful for identifying healthy BRCA1/2
      carriers with high risk of developing breast cancer; moreover, sEGFR measurements
      may serve as effective tools for assessing risk before and after BSO.

PMID- 23966580
TI  - Physical activity in different periods of life, sedentary behavior, and the risk
      of ovarian cancer in the NIH-AARP diet and health study.
AB  - BACKGROUND: Physical activity and sedentary behavior may influence ovarian cancer
      risk, but clear evidence is lacking. METHODS: We prospectively investigated the
      relations of self-reported physical activity and sedentary behavior to ovarian
      cancer incidence in a cohort of 148,892 U.S. women ages 50-71 years at baseline
      (1995-1996), who were followed through 2006. Multivariate Cox proportional hazard
      models were used to estimate relative risks (RR) and 95% confidence intervals
      (CI). We also conducted analysis by hormone use, body mass index (BMI), and
      cancer subtype. RESULTS: We identified 753 incident epithelial ovarian cancers.
      Overall, neither physical activity nor sedentary behavior at baseline was
      associated with ovarian cancer risk. Compared with women who never or rarely
      engaged in vigorous physical activity in the past year, women who reported more
      than 5 times/week of vigorous physical activity had an RR of 1.05 (95% CI, 0.84
      1.32). Women who sat 7+ hours/day had an RR of 1.05 (95% CI, 0.80-1.37) compared
      with those reporting <3 hours of sitting. The associations were not modified by
      hormone use or BMI and were similar for both serous and non-serous subtypes.
      CONCLUSIONS: Physical activity and sedentary behavior in middle and older ages
      were not associated with ovarian cancer risk. IMPACT: We found no clear support
      for a role of physical activity and sedentary behavior in ovarian cancer risk.

PMID- 23966581
TI  - High viral load identifies cervical lesions--letter.

PMID- 23966583
TI  - The effects of cocaine self-administration on dendritic spine density in the rat
      hippocampus are dependent on genetic background.
AB  - Chronic exposure to cocaine induces modifications to neurons in the brain regions
      involved in addiction. Hence, we evaluated cocaine-induced changes in the
      hippocampal CA1 field in Fischer 344 (F344) and Lewis (LEW) rats, 2 strains that
      have been widely used to study genetic predisposition to drug addiction, by
      combining intracellular Lucifer yellow injection with confocal microscopy
      reconstruction of labeled neurons. Specifically, we examined the effects of
      cocaine self-administration on the structure, size, and branching complexity of
      the apical dendrites of CA1 pyramidal neurons. In addition, we quantified spine
      density in the collaterals of the apical dendritic arbors of these neurons. We
      found differences between these strains in several morphological parameters. For
      example, CA1 apical dendrites were more branched and complex in LEW than in F344
      rats, while the spine density in the collateral dendrites of the apical dendritic
      arbors was greater in F344 rats. Interestingly, cocaine self-administration in
      LEW rats augmented the spine density, an effect that was not observed in the F344
      strain. These results reveal significant structural differences in CA1 pyramidal
      cells between these strains and indicate that cocaine self-administration has a
      distinct effect on neuron morphology in the hippocampus of rats with different
      genetic backgrounds. 

PMID- 23966582
TI  - Conceptus-derived prostaglandins regulate gene expression in the endometrium
      prior to pregnancy recognition in ruminants.
AB  - In cattle, the blastocyst hatches from the zona pellucida on days 8-9 and then
      forms a conceptus that grows and elongates into an ovoid and then filamentous
      shape between days 9 and 16. The growing conceptus synthesizes and secretes
      prostaglandins (PGs) and interferon tau (IFNT). Our hypothesis was that the ovoid
      conceptus exerts a local effect on the endometrium prior to maternal recognition
      of pregnancy on day 16 in cattle. In study one, synchronized cyclic heifers
      received no blastocysts or 20 in vitro-produced blastocysts on day 7 and their
      uteri were collected on day 13. IFNT was not detected by RIA in the uterine
      flushing samples of pregnant heifers containing multiple ovoid conceptuses;
      however, total PG levels were higher in the uterine lumen of pregnant heifers
      than in that of cyclic heifers. Microarray analysis revealed that the expression
      of 44 genes was increased in the endometria of day 13 pregnant heifers when
      compared with that in the endometria of cyclic heifers, and many of these genes
      were classical Type I IFN-stimulated genes (ISGs). In studies two and three, the
      effects of infusing PGs at the levels produced by the elongating day 14 conceptus
      into the uterine lumen of cyclic ewes on ISG expression in the endometrium were
      determined. Results indicated that the infusion of PGs increased the abundance of
      several ISGs in the endometrium. These studies support the hypothesis that the
      day 13 conceptus secretes PGs that act locally in a paracrine manner to alter
      gene expression in the endometrium prior to pregnancy recognition in cattle. 

PMID- 23966585
TI  - After 73 years, still the foundation of diving physiology research.

PMID- 23966584
TI  - Risk-taking behavior: dopamine D2/D3 receptors, feedback, and frontolimbic
      activity.
AB  - Decision-making involves frontolimbic and dopaminergic brain regions, but how
      prior choice outcomes, dopamine neurotransmission, and frontostriatal activity
      are integrated to affect choices is unclear. We tested 60 healthy volunteers
      using the Balloon Analogue Risk Task (BART) during functional magnetic resonance
      imaging. In the BART, participants can pump virtual balloons to increase
      potential monetary reward or cash out to receive accumulated reward; each pump
      presents greater risk and potential reward (represented by the pump number). In a
      separate session, we measured striatal D2/D3 dopamine receptor binding potential
      (BPND) with positron emission tomography in 13 of the participants. Losses were
      followed by fewer risky choices than wins; and during risk-taking after loss,
      amygdala and hippocampal activation exhibited greater modulation by pump number
      than after a cash-out event. Striatal D2/D3 BPND was positively related to the
      modulation of ventral striatal activation when participants decided to cash out
      and negatively to the number of pumps in the subsequent trial; but negatively
      related to the modulation of prefrontal cortical activation by pump number when
      participants took risk, and to overall earnings. These findings provide in vivo
      evidence for a potential mechanism by which dopaminergic neurotransmission may
      modulate risk-taking behavior through an interactive system of frontal and
      striatal activity. 

PMID- 23966586
TI  - Mechanical performance of spider orb webs is tuned for high-speed prey.
AB  - Spiders in the Orbiculariae spin orb webs that dissipate the mechanical energy of
      their flying prey, bringing the insects to rest and retaining them long enough
      for the spider to attack and subdue their meals. Small prey are easily stopped by
      webs but provide little energetic gain. While larger prey offer substantial
      nourishment, they are also challenging to capture and can damage the web if they
      escape. We therefore hypothesized that spider orb webs exhibit properties that
      improve their probability of stopping larger insects while minimizing damage when
      the mechanical energy of those prey exceeds the web's capacity. Large insects are
      typically both heavier and faster flying than smaller prey, but speed plays a
      disproportionate role in determining total kinetic energy, so we predicted that
      orb webs may dissipate energy more effectively under faster impacts, independent
      of kinetic energy per se. We used high-speed video to visualize the impact of
      wooden pellets fired into orb webs to simulate prey strikes and tested how
      capture probability varied as a function of pellet size and speed. Capture
      probability was virtually nil above speeds of ~3 m s(-1). However, successful
      captures do not directly measure the maximum possible energy dissipation by orb
      webs because these events include lower-energy impacts that may not significantly
      challenge orb web performance. Therefore, we also compared the total kinetic
      energy removed from projectiles that escaped orb webs by breaking through the
      silk, asking whether more energy was removed at faster speeds. Over a range of
      speeds relevant to insect flight, the amount of energy absorbed by orb webs
      increases with the speed of prey (i.e. the rates at which webs are stretched).
      Orb webs therefore respond to faster - and hence higher kinetic energy - prey
      with better performance, suggesting adaptation to capture larger and faster
      flying insect prey. This speed-dependent toughness of a complex structure
      suggests the utility of the intrinsic toughness of spider silk and/or features of
      the macro-design of webs for high-velocity industrial or military applications,
      such as ballistic energy absorption. 

PMID- 23966588
TI  - Hibernation physiology, freezing adaptation and extreme freeze tolerance in a
      northern population of the wood frog.
AB  - We investigated hibernation physiology and freeze tolerance in a population of
      the wood frog, Rana sylvatica, indigenous to Interior Alaska, USA, near the
      northernmost limit of the species' range. Winter acclimatization responses
      included a 233% increase in the hepatic glycogen depot that was subsidized by fat
      body and skeletal muscle catabolism, and a rise in plasma osmolality that
      reflected accrual of urea (to 106+/-10 MUmol ml(-1)) and an unidentified solute
      (to ~73 MUmol ml(-1)). In contrast, frogs from a cool-temperate population
      (southern Ohio, USA) amassed much less glycogen, had a lower uremia (28+/-5 MUmol
      ml(-1)) and apparently lacked the unidentified solute. Alaskan frogs survived
      freezing at temperatures as low as -16 degrees C, some 10-13 degrees C below
      those tolerated by southern conspecifics, and endured a 2-month bout of freezing
      at -4 degrees C. The profound freeze tolerance is presumably due to their high
      levels of organic osmolytes and bound water, which limits ice formation. Adaptive
      responses to freezing (-2.5 degrees C for 48 h) and subsequent thawing (4 degrees
      C) included synthesis of the cryoprotectants urea and glucose, and dehydration of
      certain tissues. Alaskan frogs differed from Ohioan frogs in retaining a
      substantial reserve capacity for glucose synthesis, accumulating high levels of
      cryoprotectants in brain tissue, and remaining hyperglycemic long after thawing.
      The northern phenotype also incurred less stress during freezing/thawing, as
      indicated by limited cryohemolysis and lactate accumulation. Post-glacial
      colonization of high latitudes by R. sylvatica required a substantial increase in
      freeze tolerance that was at least partly achieved by enhancing their
      cryoprotectant system. 

PMID- 23966587
TI  - Dose and developmental responses of Anopheles merus larvae to salinity.
AB  - Saltwater tolerance is a trait that carries both ecological and epidemiological
      significance for Anopheles mosquitoes that transmit human malaria, as it plays a
      key role in determining their habitat use and ecological distribution, and thus
      their local contribution to malaria transmission. Here, we lay the groundwork for
      genetic dissection of this trait by quantifying saltwater tolerance in three
      closely related cryptic species and malaria vectors from the Afrotropical
      Anopheles gambiae complex that are known to differ starkly in their tolerance to
      salinity: the obligate freshwater species A. gambiae and A. coluzzii, and the
      saltwater-tolerant species A. merus. We performed detailed comparisons of
      survivorship under varying salinities, using multiple strains of A. gambiae, A.
      coluzzii and A. merus, as well as F1 progeny from reciprocal crosses of A. merus
      and A. coluzzii. Additionally, using immunohistochemistry, we compared the
      location of three ion regulatory proteins (Na(+)/K(+)-ATPase, carbonic anhydrase
      and Na(+)/H(+)-antiporter) in the recta of A. coluzzii and A. merus reared in
      freshwater or saline water. As expected, we found that A. merus survives exposure
      to high salinities better than A. gambiae and A. coluzzii. Further, we found that
      exposure to a salinity level of 15.85 g NaCl l(-1) is a discriminating dose that
      kills all A. gambiae, A. coluzzii and A. coluzzii-A. merus F1 larvae, but does
      not negatively impact the survival of A. merus. Importantly, phenotypic
      expression of saltwater tolerance by A. merus is highly dependent upon the
      developmental time of exposure, and based on immunohistochemistry, salt tolerance
      appears to involve a major shift in Na(+)/K+-ATPase localization in the rectum,
      as observed previously for the distantly related saline-tolerant species A.
      albimanus. 

PMID- 23966589
TI  - Social regulation of maternal traits in nest-founding bumble bee (Bombus
      terrestris) queens.
AB  - During the nest-founding phase of the bumble bee colony cycle, queens undergo
      striking changes in maternal care behavior. Early in the founding phase, prior to
      the emergence of workers in the nest, queens are reproductive and also provision
      and feed their offspring. However, later in the founding phase, queens reduce
      their feeding of larvae and become specialized on reproduction. This transition
      is synchronized with the emergence of workers in the colony, who assume the task
      of feeding their siblings. Using a social manipulation experiment with the bumble
      bee Bombus terrestris, we tested the hypothesis that workers regulate the
      transition from feeding brood to specialization on reproduction in nest-founding
      bumble bee queens. Consistent with this hypothesis, we found that early-stage
      nest-founding queens with workers prematurely added to their nests reduce their
      brood-feeding behavior and increase egg laying, and likewise, late-stage nest
      founding queens increase their brood-feeding behavior and decrease egg-laying
      when workers are removed from their nests. Further, brood-feeding and egg-laying
      behaviors were negatively correlated. We used Agilent microarrays designed from
      B. terrestris brain expressed sequenced tags (ESTs) to explore a second
      hypothesis, that workers alter brain gene expression in nest-founding queens. We
      found evidence that brain gene expression in nest-founding queens is altered by
      the presence of workers, with the effect being much stronger in late-stage
      founding queens. This study provides new insights into how the transition from
      feeding brood to specialization on reproduction in queen bumble bees is regulated
      during the nest initiation phase of the colony cycle. 

PMID- 23966591
TI  - Thyroid hormone regulates muscle function during cold acclimation in zebrafish
      (Danio rerio).
AB  - Thyroid hormone (TH) is a universal regulator of growth, development and
      metabolism during cold exposure in mammals. In zebrafish (Danio rerio), TH
      regulates locomotor performance and metabolism during cold acclimation. The
      influence of TH on locomotor performance may be via its effect on metabolism or,
      as has been shown in mammals, by modulating muscle phenotypes. Our aim was to
      determine whether TH influences muscle phenotypes in zebrafish, and whether this
      could explain changes in swimming capacity in response to thermal acclimation. We
      used propylthiouracil and iopanoic acid to induce hypothyroidism in zebrafish
      over a 3-week acclimation period to either 18 or 28 degrees C. To verify that
      physiological changes following hypothyroid treatment were in fact due to the
      action of TH, we supplemented hypothyroid fish with 3,5-diiodothryronine (T2) or
      3,5,3'-triiodothyronine (T3). Cold-acclimated fish had significantly greater
      sustained swimming performance (Ucrit) but not burst speed. Greater Ucrit was
      accompanied by increased tail beat frequency, but there was no change in tail
      beat amplitude. Hypothyroidism significantly decreased Ucrit and burst
      performance, as well as tail beat frequency and SERCA activity in cold-acclimated
      fish. However, myofibrillar ATPase activity increased in cold-acclimated
      hypothyroid fish. Hypothyroid treatment also decreased mRNA concentrations of
      myosin heavy chain fast isoforms and SERCA 1 isoform in cold-acclimated fish.
      SERCA 1 mRNA increased in warm-acclimated hypothyroid fish, and SERCA 3 mRNA
      decreased in both cold- and warm-acclimated hypothyroid fish. Supplementation
      with either T2 or T3 restored Ucrit, burst speed, tail beat frequency, SERCA
      activity and myosin heavy chain and SERCA 1 and 3 mRNA levels of hypothyroid fish
      back to control levels. We show that in addition to regulating development and
      metabolism in vertebrates, TH also regulates muscle physiology in ways that
      affect locomotor performance in fish. We suggest that the role of TH in
      modulating SERCA1 expression during cold exposure may have predisposed it to
      regulate endothermic thermogenesis. 

PMID- 23966590
TI  - Auditory sensitivity of larval zebrafish (Danio rerio) measured using a
      behavioral prepulse inhibition assay.
AB  - Zebrafish (Danio rerio) have become a valuable model for investigating the
      molecular genetics and development of the inner ear in vertebrates. In this
      study, we employed a prepulse inhibition (PPI) paradigm to assess hearing in
      larval wild-type (AB) zebrafish during early development at 5-6 days post
      fertilization (d.p.f.). We measured the PPI of the acoustic startle response in
      zebrafish using a 1-dimensional shaker that simulated the particle motion
      component of sound along the fish's dorsoventral axis. The thresholds to startle
      inducing stimuli were determined in 5-6 d.p.f. zebrafish, and their hearing
      sensitivity was then characterized using the thresholds of prepulse tone stimuli
      (90-1200 Hz) that inhibited the acoustic startle response to a reliable startle
      stimulus (820 Hz at 20 dB re. 1 m s(-2)). Hearing thresholds were defined as the
      minimum prepulse tone level required to significantly reduce the startle response
      probability compared with the baseline (no-prepulse) condition. Larval zebrafish
      showed greatest auditory sensitivity from 90 to 310 Hz with corresponding mean
      thresholds of -19 to -10 dB re. 1 m s(-2), respectively. Hearing thresholds of
      prepulse tones were considerably lower than previously predicted by startle
      response assays. The PPI assay was also used to investigate the relative
      contribution of the lateral line to the detection of acoustic stimuli. After
      aminoglycoside-induced neuromast hair-cell ablation, we found no difference in
      PPI thresholds between treated and control fish. We propose that this PPI assay
      can be used to screen for novel zebrafish hearing mutants and to investigate the
      ontogeny of hearing in zebrafish and other fishes. 

PMID- 23966592
TI  - Induction of cotton ovule culture fibre branching by co-expression of cotton BTL,
      cotton SIM, and Arabidopsis STI genes.
AB  - The highly elongated single-celled cotton fibre consists of lint and fuzz,
      similar to the Arabidopsis trichome. Endoreduplication is an important
      determinant in Arabidopsis trichome initiation and morphogenesis. Fibre
      development is also controlled by functional homologues of Arabidopsis trichome
      patterning genes, although fibre cells do not have a branched shape like
      trichomes. The identification and characterization of the homologues of 10 key
      Arabidopsis trichome branching genes in Gossypium arboreum are reported here.
      Nuclear ploidy of fibres was determined, and gene function in cotton callus and
      fibre cells was investigated. The results revealed that the nuclear DNA content
      was constant in fuzz, whereas a limited and reversible change occurred in lint
      after initiation. Gossypeum arboreum branchless trichomes (GaBLT) was not
      transcribed in fibres. The homologue of STICHEL (STI), which is essential for
      trichome branching, was a pseudogene in Gossypium. Targeted expression of GaBLT,
      Arabidopsis STI, and the cytokinesis-repressing GaSIAMESE in G. hirsutum fibre
      cells cultured in vitro resulted in branching. The findings suggest that the
      distinctive developmental mechanism of cotton fibres does not depend on
      endoreduplication. This important component may be a relic function that can be
      activated in fibre cells.

PMID- 23966594
TI  - Not looking where you are leaping: a novel method of oriented travel in the
      caterpillar Calindoea trifascialis (Moore) (Lepidoptera: Thyrididae).
AB  - The prepupation caterpillar of the Southeast Asian moth Calindoea trifascialis
      constructs a leaf shelter that jumps across the ground using a jumping method
      novel among the insects. We found that movement path direction was correlated to
      the direction opposite to the most intense light. Correlated random walk (CRW)
      analyses found net squared displacements higher than predicted by a CRW, and
      fractal dimension analysis indicated straighter paths at large spatial scales.
      Rearing experiments showed high mortality from predation on the ground, but
      higher mortality resulted from sun exposure. We interpret jumping path
      orientation as an efficient search strategy to find shade in a variable
      landscape, given limited perception, in the presence of overheating and
      desiccation risks. 

PMID- 23966593
TI  - Analysis of the early-flowering mechanisms and generation of T-DNA tagging lines
      in Kitaake, a model rice cultivar.
AB  - As an extremely early flowering cultivar, rice cultivar Kitaake is a suitable
      model system for molecular studies. Expression analyses revealed that transcript
      levels of the flowering repressor Ghd7 were decreased while those of its
      downstream genes, Ehd1, Hd3a, and RFT1, were increased. Sequencing the known
      flowering-regulator genes revealed mutations in Ghd7 and OsPRR37 that cause early
      translation termination and amino acid substitutions, respectively. Genetic
      analysis of F2 progeny from a cross between cv. Kitaake and cv. Dongjin indicated
      that those mutations additively contribute to the early-flowering phenotype in
      cv. Kitaake. Because the short life cycle facilitates genetics research, this
      study generated 10 000 T-DNA tagging lines and deduced 6758 flanking sequence
      tags (FSTs), in which 3122 were genic and 3636 were intergenic. Among the genic
      lines, 367 (11.8%) were inserted into new genes that were not previously tagged.
      Because the lines were generated by T-DNA that contained the promoterless GUS
      reporter gene, which had an intron with triple splicing donors/acceptors in the
      right border region, a high efficiency of GUS expression was shown in various
      organs. Sequencing of the GUS-positive lines demonstrated that the third splicing
      donor and the first splicing acceptor of the vector were extensively used. The
      FST data have now been released into the public domain for seed distribution and
      facilitation of rice research. 

PMID- 23966595
TI  - European birds adjust their flight initiation distance to road speed limits.
AB  - Behavioural responses can help species persist in habitats modified by humans.
      Roads and traffic greatly affect animals' mortality not only through habitat
      structure modifications but also through direct mortality owing to collisions.
      Although species are known to differ in their sensitivity to the risk of
      collision, whether individuals can change their behaviour in response to this is
      still unknown. Here, we tested whether common European birds changed their flight
      initiation distances (FIDs) in response to vehicles according to road speed limit
      (a known factor affecting killing rates on roads) and vehicle speed. We found
      that FID increased with speed limit, although vehicle speed had no effect. This
      suggests that birds adjust their flight distance to speed limit, which may reduce
      collision risks and decrease mortality maximizing the time allocated to foraging
      behaviours. Mobility and territory size are likely to affect an individuals'
      ability to respond adaptively to local speed limits. 

PMID- 23966596
TI  - Forelimb muscle function in pig-nosed turtles, Carettochelys insculpta: testing
      neuromotor conservation between rowing and flapping in swimming turtles.
AB  - Changes in muscle activation patterns can lead to new locomotor modes; however,
      neuromotor conservation-the evolution of new forms of locomotion through changes
      in structure without concurrent changes to underlying motor patterns-has been
      documented across diverse styles of locomotion. Animals that swim using
      appendages do so via rowing (anteroposterior oscilations) or flapping
      (dorsoventral oscilations). Yet few studies have compared motor patterns between
      these swimming modes. In swimming turtles, propulsion is generated exclusively by
      limbs. Kinematically, turtles swim using multiple styles of rowing (freshwater
      species), flapping (sea turtles) and a unique hybrid style with superficial
      similarity to flapping by sea turtles and characterized by increased dorsoventral
      motions of synchronously oscillated forelimbs that have been modified into
      flippers (Carettochelys insculpta). We compared forelimb motor patterns in four
      species of turtle (two rowers, Apalone ferox and Trachemys scripta; one flapper,
      Caretta caretta; and Carettochelys) and found that, despite kinematic
      differences, motor patterns were generally similar among species with a few
      notable exceptions: specifically, presence of variable bursts for pectoralis and
      triceps in Trachemys (though timing of the non-variable pectoralis burst was
      similar), and the timing of deltoideus activity in Carettochelys and Caretta
      compared with other taxa. The similarities in motor patterns we find for several
      muscles provide partial support for neuromotor conservation among turtles using
      diverse locomotor styles, but the differences implicate deltoideus as a prime
      contributor to flapping limb motions. 

PMID- 23966597
TI  - Female plumage colour influences seasonal oxidative damage and testosterone
      profiles in a songbird.
AB  - Across diverse taxa, morphological traits mediate social interactions and mate
      selection. Physiological constraints on signal elaboration have been widely
      documented, but the potential for trait display to influence physiological state
      remains poorly understood. We tested for the presence of causal links between
      ventral plumage colour-a trait known to covary with reproductive performance-and
      physiological measures in female North American barn swallows, Hirundo rustica
      erythrogaster. Naturally darker swallows have lower levels of plasma oxidative
      damage. Females manipulated to display darker ventral plumage during reproduction
      rapidly decreased oxidative damage, adopting the physiological state of naturally
      darker individuals. These results support the presence of a social mechanism that
      links static plumage traits with the physiological state of their bearer during
      trait advertisement, long after the completion of signal development. 

PMID- 23966598
TI  - A brood parasite selects for its own egg traits.
AB  - Many brood parasitic birds lay eggs that mimic their hosts' eggs in appearance.
      This typically arises from selection from discriminating hosts that reject eggs
      which differ from their own. However, selection on parasitic eggs may also arise
      from parasites themselves, because it should pay a laying parasitic female to
      detect and destroy another parasitic egg previously laid in the same host nest by
      a different female. In this study, I experimentally test the source of selection
      on greater honeyguide (Indicator indicator) egg size and shape, which is
      correlated with that of its several host species, all of which breed in dark
      holes. Its commonest host species did not discriminate against experimental eggs
      that differed from their own in size and shape, but laying female honeyguides
      preferentially punctured experimental eggs more than host or control eggs. This
      should improve offspring survival given that multiple parasitism by this species
      is common, and that honeyguide chicks kill all other nest occupants. Hence,
      selection on egg size in greater honeyguides parasitizing bee-eaters appears to
      be imposed not by host defences but by interference competition among parasites
      themselves. 

PMID- 23966599
TI  - Deposition of pathogenic Mycoplasma gallisepticum onto bird feeders: host
      pathology is more important than temperature-driven increases in food intake.
AB  - Although ambient temperature has diverse effects on disease dynamics, few studies
      have examined how temperature alters pathogen transmission by changing host
      physiology or behaviour. Here, we test whether reducing ambient temperature
      alters host foraging, pathology and the potential for fomite transmission of the
      bacterial pathogen Mycoplasma gallisepticum (MG), which causes seasonal outbreaks
      of severe conjunctivitis in house finches (Haemorhous mexicanus). We housed
      finches at temperatures within or below the thermoneutral zone to manipulate food
      intake by altering energetic requirements of thermoregulation. We predicted that
      pathogen deposition on bird feeders would increase with temperature-driven
      increases in food intake and with conjunctival pathology. As expected, housing
      birds below the thermoneutral zone increased food consumption. Despite this
      difference, pathogen deposition on feeders did not vary across temperature
      treatments. However, pathogen deposition increased with conjunctival pathology,
      independently of temperature and pathogen load, suggesting that MG could enhance
      its transmission by increasing virulence. Our results suggest that in this
      system, host physiological responses are more important for transmission
      potential than temperature-dependent alterations in feeding. Understanding such
      behavioural and physiological contributions to disease transmission is critical
      to linking individual responses to climate with population-level disease
      dynamics. 

PMID- 23966600
TI  - Analysis of the prevalence rate and correlative risk factors of chronic kidney
      disease in physical checkups of adults in Henan area.
AB  - This paper reports the results of physical examination data of a population aged
      19 years and above in the Henan area. The prevalence of Chronic Kidney Disease
      (CKD) in adults in a healthy population and associations with potential risk
      factors are described. There were 556 cases with albuminuria, a prevalence rate
      of 5.09% (95% CI: 3.19-6.88). The prevalence rate of males (5.87%) was higher
      than that of females (3.81%). There were 278 cases with eGFR <60 mL/min.(1.73
      m(2))(-1), suggesting a high rate of unreported CKD in this community. 

PMID- 23966601
TI  - Meta-analysis of the correlation between PTPN22 gene polymorphisms and
      susceptibility to systemic lupus erythematosus.
AB  - In this meta-analysis of the association between PTPN22 gene polymorphisms and
      susceptibility to systemic lupus erythematosus, 4 case-control studies, including
      one from China, were included. The studies included 1864 participants: 772 cases
      and 1092 controls. The meta-analysis showed that the 1858C/T polymorphism of the
      PTPN22 gene is correlated with systemic lupus erythematosus susceptibility, when
      assessed by distribution characteristics such as nationality, race, and region. A
      large sample size from the Chinese population is required for a further
      prospective study before causality can be established. 

PMID- 23966602
TI  - Time-of-flight mass spectrometry in screening serum-specific protein in patients
      with scrotal Paget's disease.
AB  - The weak cationic chip (WCX2) and the surface-enhanced laser
      desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) were used
      to test the serum differential proteins in 20 healthy persons, 20 patients with
      chronic scrotal eczema, and 30 patients with scrotal Paget's disease and test the
      specificity and sensitivity of screening scrotal Paget's disease with
      differential proteins. We found that the differences between the 5 protein peaks
      of the normal group and the scrotal Paget's disease group in the range of 2000 to
      30 000 Da were statistically significant (P < .01) and the difference of 3
      protein peaks between the scrotal eczema group and the scrotal Paget's disease
      group in the range of 2000 to 30 000 Da was statistically significant (P < .05).
      SELDI-TOS-MS technique has certain application value in the early diagnosis of
      the scrotal Paget's disease and screening for the specific tumor markers. 

PMID- 23966603
TI  - A cross-sectional survey of dental caries, oral hygiene, and Helicobacter pylori
      infection in adults.
AB  - We explored the epidemiological risk factors for dental caries to help explain
      differences in the prevalence of adult dental caries. We examined 841 people for
      the presence of Helicobacter pylori in their dental plaque and for dental caries.
      Of the 841 subjects, 574 (68.25%) were infected with H pylori, and 516 (61.36%)
      were diagnosed with dental caries. Among the 574 subjects with H pylori, the
      prevalence of dental caries was 73.52% (422/574), while the prevalence among the
      267 cases without H pylori was 35.21% (94/267). A correlation existed between the
      presence of H pylori and the occurrence of dental caries (chi(2) = 112.8, P <
      .01, odds ratio = 5.110, 95% confidence interval = 3.740-6.982). The 574 persons
      with H pylori had a higher mean dental plaque index than those without. In
      conclusion, H pylori infection in the oral cavity is associated with dental
      caries and poor dental hygiene. 

PMID- 23966604
TI  - Environment, heredity, and epidemiology.

PMID- 23966605
TI  - Investigation of the risk factors for leukoaraiosis (LA).
AB  - Leukoaraiosis (LA) describes abnormal changes in the cerebral white matter
      frequently seen on CT and MRI in older adults. Its appearance indicates mild
      brain injury, and it is often regarded as a mark of senile dementia. Through the
      analysis of related risk factors of 6000 patients with LA diagnosed by cranial
      MRI in our department, we found that age, cerebral infarction, lacunar
      infarction, history of brain hemorrhage, and increased triglycerides were risk
      factors for LA, and the relative risk odds ratio values were 2.135 (95%
      confidence interval [CI] = 1.874-2.501), 3.330 (95% CI = 1.922-3.997), 3.412 (95%
      CI = 2.986-3.512), 3.611 (95% CI = 2.054-9.147), and 1.457 (95% CI = 1.058
      1.769), respectively. Through the identification of the risk factors for LA and
      effective interventions, the occurrence of dementia, stroke, and premature death
      may be effectively prevented. 

PMID- 23966606
TI  - Genetics and the future of public health.

PMID- 23966607
TI  - Effect of synthetic pyrethroid pesticide exposure during pregnancy on the growth
      and development of infants.
AB  - Antenatal urine of 497 pregnant women was collected in the Department of
      Gynecology and Obstetrics of a county hospital in Jiaozuo, Henan. The content of
      the main metabolites of synthetic pyrethroid pesticides in urine were determined.
      After 1 year, physical development indices of 1-year old infants, such as height,
      weight, and head and chest circumference, were measured. The neural and mental
      development of the infants was assessed by the Development Screen Test (DST)
      scale. We observed that the level of synthetic pyrethroid pesticide exposure was
      negatively related to the neural and mental development of infants (beta = 
      0.1527, P < 0.05). Therefore, direct or indirect exposure to synthetic pyrethroid
      pesticides should be avoided during pregnancy. 

PMID- 23966608
TI  - Effect of leptin receptor mutation on the development of chronic bronchitis.
AB  - To investigate the effect of serum leptin level and leptin receptor (Lepr)
      genetic mutation on chronic bronchitis, we measured the serum leptin levels of
      236 patients with chronic bronchitis and 107 healthy controls by ELISA, the
      genotype distribution of Lepr gene containing Gln223Arg polymorphic sites by the
      polymerase chain reaction-restriction fragment length polymorphism (RFLP) method,
      the levels of inflammatory markers in serum, and the concentration of
      neutrophils. We found that the GG genotype distribution and G gene frequency of
      Lepr gene Gln223Arg site of the patient group were higher than that in the
      control group. The serum high-sensitivity C-reactive protein and neutrophil
      granulocyte levels of the patient group were higher than those of the control
      group. But the leptin concentrations of those with GG genotype were lower than
      those with AA+AG genotype (P < .05). The mutation of Lepr gene Gln223Arg site may
      not directly influence the leptin level but could possibly advance the disease
      through inhibiting the biological effect of leptin. 

PMID- 23966609
TI  - A cross-sectional study of associations between nonsynonymous mutations of the
      BARD1 gene and breast cancer in Han Chinese women.
AB  - The PCR-PIRA and PCR-RFLP techniques were used for BARD1 genotyping. Correlations
      between gene polymorphisms and the susceptibility to breast cancer were analyzed
      by logistic regression analysis. RESULTS: showed that compared with the wild type
      of 378 Arg/Arg of BRAD1, the homozygotic type of 378 Ser/Ser with Arg378Ser site
      mutation had a protective effect (adjusted odds ratio: 0.628, 95% confidence
      interval: 0.306-1.145). Compared with individuals carrying the wild type of
      24Pro/Pro, the disease risk of individuals with the heterozygous type of 24
      Pro/Ser decreased by 30.6% and that with the mutational homozygotic type of 24
      Ser/Ser decreased by 43.8%. SNP sites rs2229571 and rs1048108 of BARD1 are
      associated with a lower risk of breast cancer but not rs2070094.

PMID- 23966614
TI  - miR-335 inhibits small cell lung cancer bone metastases via IGF-IR and RANKL
      pathways.
AB  - Small cell lung cancer (SCLC) is a rapidly progressing, incurable cancer that
      frequently spreads to bone. New insights are needed to identify therapeutic
      targets to prevent or retard SCLC metastatic progression. Human SCLC SBC-5 cells
      in mouse xenograft models home to skeletal and nonskeletal sites, whereas human
      SCLC SBC-3 cells only pervade nonskeletal sites. Because microRNAs (miRNA) often
      act as tumor regulators, we investigated their role in preclinical models of
      SCLC. miRNA expression profiling revealed selective and reduced expression of
      miRNA (miR)-335 and miR-29a in SBC-5 cells, compared with SBC-3 cells. In SBC-5
      cells, miR-335 expression correlated with bone osteolytic lesions, whereas miR
      29a expression did not. Overexpression of miR-335 in SBC-5 cells significantly
      reduced cell migration, invasion, proliferation, colony formation, and osteoclast
      induction in vitro. Importantly, in miR-335 overexpressing SBC-5 cell xenografts
      (n = 10), there were minimal osteolytic lesions in the majority of mice and none
      in three mice. Expression of RANK ligand (RANKL) and insulin-like growth factor-I
      receptor (IGF-IR), key mediators of bone metastases, were elevated in SBC-5 as
      compared with SBC-3 cells. Mechanistically, overexpression of miR-335 in SBC-5
      cells reduced RANKL and IGF-IR expression. In conclusion, loss of miR-335
      promoted SCLC metastatic skeletal lesions via deregulation of IGF-IR and RANKL
      pathways and was associated with metastatic osteolytic skeletal lesions.
      IMPLICATIONS: These preclinical findings establish a need to pursue the role of
      miR-335 in human SCLC with metastatic skeletal disease.

PMID- 23966615
TI  - Defining the relationship between fetal Doppler indices, abdominal circumference
      and growth rate in severe fetal growth restriction using functional linear
      discriminant analysis.
AB  - The relationship between Doppler measurements, size and growth rate in fetal
      growth restriction has not been defined. We used functional linear discriminant
      analysis (FLDA) to investigate these parameters taking account of the
      difficulties inherent in exploring relationships between repeated observations
      from a small number of cases. In 40 fetuses with severe growth restriction,
      serial abdominal circumference (AC), umbilical, middle cerebral artery (MCA) and
      ductus venosus Doppler pulsatility index measurements were recorded. In 11
      singleton fetuses with normal growth, umbilical artery pulsatility index only was
      measured. Data were expressed as z-scores in relation to gestation and analysed
      longitudinally using FLDA. In severe growth restriction, the Spearman correlation
      coefficients between umbilical artery pulsatility index and AC z-score, MCA
      pulsatility index and AC z-score and ductus venosus pulsatility index z-score and
      AC z-score were, respectively: -0.36, p = 4.4 * 10(-7); 0.70, p = 1.1 * 10(-17)
      and -0.50, p = 8.1 * 10(-4). No relationship was seen between Doppler parameters
      and growth rate. There was no relationship between umbilical artery pulsatility
      index and AC nor growth rate in normally grown fetuses. In severe fetal growth
      restriction, Doppler changes are related to absolute fetal AC size, not growth
      rate. 

PMID- 23966616
TI  - Towards a richer evolutionary game theory.
AB  - Most examples of the application of evolutionary game theory to problems in
      biology involve highly simplified models. I contend that it is time to move on
      and include much more richness in models. In particular, more thought needs to be
      given to the importance of (i) between-individual variation; (ii) the interaction
      between individuals, and hence the process by which decisions are reached; (iii)
      the ecological and life-history context of the situation; (iv) the traits that
      are under selection, and (v) the underlying psychological mechanisms that lead to
      behaviour. I give examples where including variation between individuals
      fundamentally changes predicted outcomes of a game. Variation also selects for
      real-time responses, again resulting in changed outcomes. Variation can select
      for other traits, such as choosiness and social sensitivity. More generally, many
      problems involve coevolution of more than one trait. I identify situations where
      a reductionist approach, in which a game is isolated from is ecological setting,
      can be misleading. I also highlight the need to consider flexibility of
      behaviour, mental states and other issues concerned with the evolution of
      mechanism. 

PMID- 23966617
TI  - Microfluidic one-step synthesis of alginate microspheres immobilized with
      antibodies.
AB  - Micrometre- and submicrometre-size functionalized beads are frequently used to
      capture targets of interest from a biological sample for biological
      characterizations and disease diagnosis. The main challenge of the microbead
      based assay is in the immobilization of probe molecules onto the microbead
      surfaces. In this paper, we report a versatile droplet microfluidics method to
      fabricate alginate microspheres while simultaneously immobilizing anti
      Mycobacterium tuberculosis complex IgY and anti-Escherichia coli IgG antibodies
      primarily on the porous alginate carriers for specific binding and binding
      affinity tests. The binding affinity of antibodies is directly measured by
      fluorescence intensity of stained target bacteria on the microspheres. We
      demonstrate that the functionalized alginate microspheres yield specificity
      comparable with an enzyme-linked immunosorbent assay. The high surface area-to
      volume ratio of the functionalized porous alginate microspheres improves the
      detection limit. By using the droplet microfluidics, we can easily modify the
      size and shape of alginate microspheres, and increase the concentration of
      functionalized alginate microspheres to further enhance binding kinetics and
      enable multiplexing. 

PMID- 23966618
TI  - Negative feedback self-regulation contributes to robust and high-fidelity
      transmembrane signal transduction.
AB  - We present a minimal motif model for transmembrane cell signalling. The model
      assumes signalling events taking place in spatially distributed nanoclusters
      regulated by a birth/death dynamics. The combination of these spatio-temporal
      aspects can be modulated to provide a robust and high-fidelity response behaviour
      without invoking sophisticated modelling of the signalling process as a sequence
      of cascade reactions and fine-tuned parameters. Our results show that the fact
      that the distributed signalling events take place in nanoclusters with a finite
      lifetime regulated by local production is sufficient to obtain a robust and high
      fidelity response. 

PMID- 23966619
TI  - Magnetoreception: activated cryptochrome 1a concurs with magnetic orientation in
      birds.
AB  - The radical pair model proposes that the avian magnetic compass is based on
      radical pair processes in the eye, with cryptochrome, a flavoprotein, suggested
      as receptor molecule. Cryptochrome 1a (Cry1a) is localized at the discs of the
      outer segments of the UV/violet cones of European robins and chickens. Here, we
      show the activation characteristics of a bird cryptochrome in vivo under natural
      conditions. We exposed chickens for 30 min to different light regimes and
      analysed the amount of Cry1a labelled with an antiserum against an epitope at the
      C-terminus of this protein. The staining after exposure to sunlight and to
      darkness indicated that the antiserum labels only an illuminated, activated form
      of Cry1a. Exposure to narrow-bandwidth lights of various wavelengths revealed
      activated Cry1a at UV, blue and turquoise light. With green and yellow, the
      amount of activated Cry1a was reduced, and with red, as in the dark, no activated
      Cry1a was labelled. Activated Cry1a is thus found at all those wavelengths at
      which birds can orient using their magnetic inclination compass, supporting the
      role of Cry1a as receptor molecule. The observation that activated Cry1a and well
      oriented behaviour occur at 565 nm green light, a wavelength not absorbed by the
      fully oxidized form of cryptochrome, suggests that a state other than the
      previously suggested Trp/FAD radical pair formed during photoreduction is crucial
      for detecting magnetic directions.

PMID- 23966621
TI  - Synergistic targeting of PI3K/AKT pathway and androgen receptor axis
      significantly delays castration-resistant prostate cancer progression in vivo.
AB  - The progression to castration-resistant prostate cancer (CRPC) correlates with
      gain-of-function of the androgen receptor (AR) and activation of AKT. However, as
      single agents, AR or AKT inhibitors result in a reciprocal feedback loop.
      Therefore, we hypothesized that combination of an AKT inhibitor with an
      antiandrogen might result in a more profound, long-lasting remission of CRPC.
      Here, we report that the AKT inhibitor AZD5363 potently inhibits proliferation
      and induces apoptosis in prostate cancer cell lines expressing the AR and has
      anticancer activity in vivo in androgen-sensitive and castration-resistant phases
      of the LNCaP xenograft model. However, we found that the effect of castration
      resistant tumor growth inhibition and prostate-specific antigen (PSA)
      stabilization is transient and resistance occurs with increasing PSA after
      approximately 30 days of treatment. Mechanistically, we found that single agent
      AZD5363 induces increase of AR binding to androgen response element, AR
      transcriptional activity, and AR-dependent genes such as PSA and NKX3.1
      expression. These effects were overcome by the combination of AZD5363 with the
      antiandrogen bicalutamide, resulting in synergistic inhibition of cell
      proliferation and induction of apoptosis in vitro, and prolongation of tumor
      growth inhibition and PSA stabilization in CRPC in vivo. This study provides a
      preclinical proof-of-concept that combination of an AKT inhibitor with
      antiandrogen results in prolonged disease stabilization in a model of CRPC.

PMID- 23966620
TI  - Hsp90 inhibitors promote p53-dependent apoptosis through PUMA and Bax.
AB  - Hsp90 is widely overexpressed in cancer cells and believed to be essential for
      the maintenance of malignant phenotypes. Targeting Hsp90 by small molecules has
      shown promise in solid and hematologic malignancies, which likely involves
      degradation of client oncoproteins in a cell-type-specific manner. In this study,
      we found that structurally unrelated Hsp90 inhibitors induce DNA damage and
      apoptosis via p53-dependent induction of PUMA, which indirectly triggers Bax
      activation and mitochondrial dysfunction in colon cancer cells. Deficiency in
      PUMA, BAX, or p53, at lesser extent, abrogated 17-allylamino-17
      demethoxygeldanamycin (17-AAG)-induced apoptosis and mitochondrial dysfunction,
      and enhanced clonogenic cell survival. Furthermore, suppression of p53-dependent
      p21 induction or enhanced p53 activation synergized with 17-AAG to induce PUMA
      dependent apoptosis. Finally, PUMA was found to mediate apoptotic and therapeutic
      responses to the 17-AAG analog 17-DMAG in xenografts. These results show an
      important role of the p53/PUMA/Bax axis in Hsp90 inhibitor-induced killing of p53
      wild-type cells, and have important implications for their clinical applications.

PMID- 23966622
TI  - Combining PARP-1 inhibition and radiation in Ewing sarcoma results in lethal DNA
      damage.
AB  - Ewing sarcomas (ES) harbor a chromosomal translocation that fuses the EWS gene to
      an ETS transcription factor, most commonly Friend leukemia integration 1 (FLI1).
      The EWS-FLI1 fusion protein acts in a positive feedback loop to maintain the
      expression of PARP-1, which is involved in repair of DNA damage. Here, we examine
      the effects of PARP-1 inhibition and radiation therapy on Ewing sarcomas. In
      proliferation assays, the Ewing sarcoma cell lines RD-ES and SK-N-MC were much
      more sensitive than non-Ewing sarcoma cell lines to the PARP-1 inhibitor olaparib
      (Ola; IC50 0.5-1 MUmol/L vs. >5 MUmol/L) and to radiation (IC50 2-4 Gy vs. >6
      Gy). PARP-1 inhibition with short hairpin RNA (shRNA) or Ola sensitized Ewing
      sarcoma cells, but not non-Ewing sarcoma cells, to radiation therapy in both
      proliferation and colony formation assays. Using the Comet assay, radiation of
      Ewing sarcoma cells with Ola, compared to without Ola, resulted in more DNA
      damage at 1 hour (mean tail moment 36-54 vs. 26-28) and sustained DNA damage at
      24 hours (24-29 vs. 6-8). This DNA damage led to a 2.9- to 4.0-fold increase in
      apoptosis and a 1.6- to 2.4-fold increase in cell death. The effect of PARP-1
      inhibition and radiation therapy on Ewing sarcoma cells was lost when EWS-FLI1
      was silenced by shRNA. A small dose of radiation therapy (4 Gy), when combined
      with PARP-1 inhibition, stopped the growth of SK-N-MC flank tumors xenografts. In
      conclusion, PARP-1 inhibition in Ewing sarcomas amplifies the level and duration
      of DNA damage caused by radiation therapy, leading to synergistic increases in
      apoptosis and cell death in a EWS-FLI1-dependent manner.

PMID- 23966623
TI  - CD28 sensitizes TCR Ca2+ signaling during Ag-independent polarization of plasma
      membrane rafts.
AB  - T cells become polarized during initial interactions with an APC to form an Ag
      independent synapse (AIS) composed of membrane rafts, TCR, and TCR-proximal
      signaling molecules. AISs occur temporally before TCR triggering, but their role
      in downstream TCR signaling is not understood. Using both human and murine model
      systems, we studied the signals that activate AIS formation and the effect of
      these signals on TCR-dependent responses. We show that CD28 produces AISs
      detectable by spinning disc confocal microscopy seconds following initial
      interactions between the T cell and APC. AIS formation by CD28 coincided with
      costimulatory signaling, evidenced by a cholesterol-sensitive activation of the
      MAPK ERK that potentiated Ca2+ signaling in response to CD3 cross-linking. CD45
      also enriched in AISs but to modulate Src kinase activity, because localization
      of CD45 at the cell interface reduced the activation of proximal Lck. In summary,
      we show that signaling by CD28 during first encounters between the T cell and APC
      both sensitizes TCR Ca2+ signaling by an Erk-dependent mechanism and drives
      formation of an AIS that modulates the early signaling until TCR triggering
      occurs. Thus, early Ag-independent encounters are an important window for
      optimizing T cell responses to Ag by CD28.

PMID- 23966624
TI  - Transcriptional regulation of IL-15 expression during hematopoiesis.
AB  - Dendritic cells (DCs) are the most commonly studied source of the cytokine IL-15.
      Using an IL-15 reporter transgenic mouse, we have recently shown previously
      unappreciated differences in the levels of IL-15 expressed by subsets of
      conventional DCs (CD8+ and CD8-). In this study, we show that IL-15 promoter
      activity was differentially regulated in subsets of hematopoietically derived
      cells with IL-15 expression largely limited to myeloid lineages. In contrast,
      mature cells of the lymphoid lineages expressed little to no IL-15 activity.
      Surprisingly, we discovered that hematopoietic stem cells (lineage-Sca-1+c-Kit+)
      expressed high levels of IL-15, suggesting that IL-15 expression was extinguished
      during lymphoid development. In the case of T cells, this downregulation was
      Notch-dependent and occurred in a stepwise pattern coincident with increasing
      maturation and commitment to a T cell fate. Finally, we further demonstrate that
      IL-15 expression was also controlled throughout DC development, with key
      regulatory activity of IL-15 production occurring at the pre-DC branch point,
      leading to the generation of both IL-15+CD8+ and IL-15(-/low)CD8- DC subsets.
      Thus, IL-15 expression is coordinated with cellular fate in myeloid versus
      lymphoid immune cells.

PMID- 23966626
TI  - Reduced T-dependent humoral immunity in CD20-deficient mice.
AB  - CD20 is a tetraspanning membrane protein expressed on B lymphocytes. CD20
      deficiency in both mice and humans has recently been shown to have deleterious
      effects on Ab responses to T-independent Ags; however, no effect on T-dependent
      immunity has been reported. In this study, we used a Cd20-/- mouse line to
      evaluate Ab responses to adeno-associated virus and SRBCs. The neutralizing Ab
      response to adeno-associated virus was significantly reduced by CD20 deficiency;
      both primary (IgM) and secondary (IgG1 and IgG2b) responses to SRBC were also
      reduced in Cd20-/- mice, and this was associated with a reduction in the number
      of germinal center B cells. A successful humoral response requires the
      integration of intracellular signaling networks that critically rely on calcium
      mobilization. In this article, we confirm that BCR-mediated calcium mobilization
      is reduced in Cd20-/- murine B cells after BCR stimulation in vitro, and further
      show that the reduction is due to an effect on calcium influx rather than calcium
      release from intracellular stores. Calcium-dependent upregulation of CD69 was
      impaired in CD20-deficient B cells, as was upregulation of CD86. Altogether, this
      study demonstrates a role for CD20 in B cell activation and T-dependent humoral
      immunity.

PMID- 23966627
TI  - Apoptosis-associated speck-like protein containing a caspase recruitment domain
      inflammasomes mediate IL-1beta response and host resistance to Trypanosoma cruzi
      infection.
AB  - The innate immune response to Trypanosoma cruzi infection comprises several
      pattern recognition receptors (PRRs), including TLR-2, -4, -7, and -9, as well as
      the cytosolic receptor Nod1. However, there are additional PRRs that account for
      the host immune responses to T. cruzi. In this context, the nucleotide-binding
      oligomerization domain-like receptors (NLRs) that activate the inflammasomes are
      candidate receptors that deserve renewed investigation. Following pathogen
      infection, NLRs form large molecular platforms, termed inflammasomes, which
      activate caspase-1 and induce the production of active IL-1beta and IL-18. In
      this study, we evaluated the involvement of inflammasomes in T. cruzi infection
      and demonstrated that apoptosis-associated speck-like protein containing a
      caspase recruitment domain (ASC) inflammasomes, including NLR family, pyrin
      domain-containing 3 (NLRP3), but not NLR family, caspase recruitment domain
      containing 4 or NLR family, pyrin domain-containing 6, are required for
      triggering the activation of caspase-1 and the secretion of IL-1beta. The
      mechanism by which T. cruzi mediates the activation of the ASC/NLRP3 pathway
      involves K+ efflux, lysosomal acidification, reactive oxygen species generation,
      and lysosomal damage. We also demonstrate that despite normal IFN-gamma
      production in the heart, ASC-/- and caspase-1-/- infected mice exhibit a higher
      incidence of mortality, cardiac parasitism, and heart inflammation. These data
      suggest that ASC inflammasomes are critical determinants of host resistance to
      infection with T. cruzi.

PMID- 23966628
TI  - Vascular endothelial growth factor-D-mediated blockade of regulatory T cells
      within tumors is induced by hematopoietic stem cell transplantation.
AB  - Lymphopenia-induced homeostatic proliferation of T cells after autologous
      hematopoietic stem cell transplantation (HSCT) skews the T cell repertoire by
      engaging tumor-associated Ags, leading to an induction of antitumor immunity.
      However, how HSCT alters the immunosuppressive microenvironment in the tumors is
      unknown. In this study, we first analyzed the kinetics of regulatory T cells
      (Tregs) in the tumors after syngeneic HSCT. Unexpectedly, the frequency of CD4+
      cells expressing Foxp3 was increased in the spleens, whereas the frequency was
      clearly decreased in the tumors after HSCT. The origin of reconstituted CD4+ and
      Foxp3+ cells in the tumors was mainly from the expansion of transferred splenic T
      cells. Then, to examine the mechanism of Treg suppression after HSCT, we isolated
      CD11c+ cells from tumors. A large amount of Treg-inhibitory cytokine IL-6 was
      secreted from the CD11c+ cells in the tumors, but not in the spleens in the
      recipient mice. Furthermore, to understand what factor affects the activity of
      CD11c+ cells in the tumors after HSCT, we analyzed the expression of various
      cytokines/chemokines with mouse cytokine Ab arrays, and noticed that VEGF-D
      concentration was increased in the tumors in the early period after HSCT. The
      CD11c+ cells produced IL-6 in response to VEGF-D stimulation, and an
      administration of VEGF receptor-3 neutralizing Ab significantly suppressed the
      production of IL-6 from CD11c+ cells accompanied with the increase of Tregs in
      the tumors of HSCT recipients. Autologous HSCT creates an environment that
      strongly supports the enhancement of antitumor immunity in reconstituted
      lymphopenic recipients through the suppression of Tregs.

PMID- 23966625
TI  - T cell-derived IL-17 mediates epithelial changes in the airway and drives
      pulmonary neutrophilia.
AB  - Th17 cells are a proinflammatory subset of effector T cells that have been
      implicated in the pathogenesis of asthma. Their production of the cytokine IL-17
      is known to induce local recruitment of neutrophils, but the direct impact of IL
      17 on the lung epithelium is poorly understood. In this study, we describe a
      novel mouse model of spontaneous IL-17-driven lung inflammation that exhibits
      many similarities to asthma in humans. We have found that STAT3 hyperactivity in
      T lymphocytes causes an expansion of Th17 cells, which home preferentially to the
      lungs. IL-17 secretion then leads to neutrophil infiltration and lung epithelial
      changes, in turn leading to a chronic inflammatory state with increased mucus
      production and decreased lung function. We used this model to investigate the
      effects of IL-17 activity on airway epithelium and identified CXCL5 and MIP-2 as
      important factors in neutrophil recruitment. The neutralization of IL-17 greatly
      reduces pulmonary neutrophilia, underscoring a key role for IL-17 in promoting
      chronic airway inflammation. These findings emphasize the role of IL-17 in
      mediating neutrophil-driven pulmonary inflammation and highlight a new mouse
      model that may be used for the development of novel therapies targeting Th17
      cells in asthma and other chronic pulmonary diseases. 

PMID- 23966629
TI  - IL-7 modulates in vitro and in vivo human memory T regulatory cell functions
      through the CD39/ATP axis.
AB  - The heterogeneity of human regulatory T cells (Tregs) may explain the
      discrepancies between studies on Tregs in physiology and pathology. Contrasting
      effects of IL-7 on the expansion and survival of human Tregs were reported.
      Therefore, we investigated the effects of IL-7 on the phenotype and function of
      well-characterized populations of human Tregs. We show that IL-7 signals via the
      CD127 receptor on naive, memory, and activated memory Tregs sorted from the blood
      of healthy donors, but it does not affect their proliferation. In contrast, IL-7
      affects their suppressive capacities differently. This effect was modest on naive
      Tregs but was dramatic (90%) on memory Tregs. We provide evidence that IL-7
      exerts a synergistic effect through downmodulation of the ectoenzyme CD39, which
      converts ATP to ADP/AMP, and an increase in ATP receptor P2X7. Both effects lead
      to an increase in the ATP-mediated effect, tipping the balance to favor Th17
      conversion. Using an IL-7 therapeutic study, we show that IL-7 exerts the same
      effects in vitro and in vivo in HIV-infected individuals. Globally, our data show
      that IL-7 negatively regulates Tregs and contributes to increase the number of
      tools that may affect Treg function in pathology. 

PMID- 23966631
TI  - Human CD1c+ myeloid dendritic cells acquire a high level of retinoic acid
      producing capacity in response to vitamin D3.
AB  - All-trans-retinoic acid (RA) plays a critical role in maintaining immune
      homeostasis. Mouse intestinal CD103+ dendritic cells (DCs) produce a high level
      of RA by highly expressing retinal dehydrogenase (RALDH)2, an enzyme that
      converts retinal to RA, and induce gut-homing T cells. However, it has not been
      identified which subset of human DCs produce a high level of RA. In this study,
      we show that CD1c+ blood myeloid DCs (mDCs) but not CD141(high) mDCs or
      plasmacytoid DCs exhibited a high level of RALDH2 mRNA and aldehyde dehydrogenase
      (ALDH) activity in an RA- and p38-dependent manner when stimulated with 1alpha,25
      dihydroxyvitamin D3 (VD3) in the presence of GM-CSF. The ALDH activity was
      abrogated by TLR ligands or TNF. CD103- rather than CD103+ human mesenteric lymph
      node mDCs gained ALDH activity in response to VD3. Furthermore, unlike in humans,
      mouse conventional DCs in the spleen and mesenteric lymph nodes gained ALDH
      activity in response to GM-CSF alone. RALDH2(high) CD1c+ mDCs stimulated naive
      CD4+ T cells to express gut-homing molecules and to produce Th2 cytokines in an
      RA-dependent manner. This study suggests that CD1c+ mDCs are a major human DC
      subset that produces RA in response to VD3 in the steady state. The "vitamin D
      CD1c+mDC-RA" axis may constitute an important immune component for maintaining
      tissue homeostasis in humans.

PMID- 23966630
TI  - Guanine modification of inhibitory oligonucleotides potentiates their suppressive
      function.
AB  - Inhibitory TLR7 and/or TLR9 oligonucleotides (inhibitory oligonucleotide [INH
      ODN]) are characterized by a phosphorothioate backbone and a CC(T)XXX3-5GGG
      motif, respectively. INH-ODN 2088 is a prototypic member of this class of INH-ODN
      and acts as a TLR7 and TLR9 antagonist. It contains a G quadruple that leads to
      higher order structures by the formation of G tetrads. These structures are
      unfavorable for the prediction of their pharmacological and immunological
      behavior. We show in this study that modification of Gs within the G quadruple by
      7-deaza-guanine or 7-deaza-2'-O-methyl-guanine avoids higher order structures and
      improves their inhibitory potential. Whereas TLR9-induced TNF-alpha secretion of
      bone marrow-derived macrophages and conventional dendritic cells was equally
      inhibited by INH-ODN 2088 and G-modified INH-ODNs such as INH-ODN 24888, TLR7
      induced TNF-alpha release and TLR7- and TLR9-induced IL-12p40 release were
      significantly more impaired by G-modified INH-ODNs. Similarly, the IL-6 release
      of B cells from wild-type and autoimmune MRL/Mp-lpr/lpr mice was more efficiently
      impaired by G-modified INH-ODNs. Surprisingly, INH-ODN 2088 stimulated B cells to
      proliferate when used in higher doses. Finally, in vivo, in wild-type and
      autoimmune MRL/Mp-lpr/lpr mice, G-modified INH-ODN 24888 was significantly more
      efficient than unmodified INH-ODN 2088. In summary, G modification allows the
      development of INH-ODNs with superior inhibitory potency for inflammatory
      diseases with high medical need such as systemic lupus erythematosus.

PMID- 23966632
TI  - Phosphatase Wip1 is essential for the maturation and homeostasis of medullary
      thymic epithelial cells in mice.
AB  - Thymic epithelial cells (TECs) are a key cell type in the thymic microenvironment
      essential for T cell development. However, intrinsic molecular mechanisms
      controlling TEC differentiation and activities are poorly defined. In this study,
      we found that deficiency of p53-induced phosphatase 1 (Wip1) in mice selectively
      caused severe medullary TEC (mTEC) maturation defects in an intrinsic manner.
      Wip1 knockout (KO) mice had decreased mature epithelial cell adhesion
      molecule+Ulex europaeus agglutinin-1 (UEA-1)+mTECs, including UEA-1+MHC class
      II(high), UEA-1+CD80+, UEA-1+CD40+, and UEA-1+Aire+ cells, but not decreased
      numbers of cortical epithelial cell adhesion molecule+BP-1+ TECs, in the
      postnatal stage but not in the fetal stage. Wip1-deficient mTECs express fewer
      tissue-restricted Ags and UEA-1+involucrin+ terminal-differentiated cells. Animal
      models, including grafting fetal Wip1-deficient thymic tissue into T cell
      deficient nude mice and reconstitution of lethally irradiated Wip1KO mouse
      recipients with wild-type bone marrow cells, also showed the impaired mTEC
      components in Wip1KO thymi, indicating the intrinsic regulatory role of Wip1 in
      mTEC maturation. Furthermore, thymus regeneration was significantly less
      efficient in adult Wip1KO mice than in wild-type mice after cyclophosphamide
      treatment. Wip1 deficiency resulted in elevated p38 MAPK activity in mTECs.
      Activated p38 MAPK has the ability to suppress CD40 expression on mTECs. Wip1
      deficient thymi displayed poor response to CD40L in the fetal thymus organ
      culture system. Thus, Wip1 positively controls mTEC maturation, homeostasis, and
      regeneration through limiting the p38 MAPK pathway.

PMID- 23966634
TI  - Chromosome scale genome assembly and transcriptome profiling of Nannochloropsis
      gaditana in nitrogen depletion.
AB  - Nannochloropsis is rapidly emerging as a model organism for the study of biofuel
      production in microalgae. Here, we report a high-quality genomic assembly of
      Nannochloropsis gaditana, consisting of large contigs, up to 500 kbp long, and
      scaffolds that in most cases span the entire length of the chromosomes. We
      identified 10646 complete genes and characterized possible alternative
      transcripts. The annotation of the predicted genes and the analysis of cellular
      processes revealed traits relevant for the genetic improvement of this organism
      such as genes involved in DNA recombination, RNA silencing, and cell wall
      synthesis. We also analyzed the modification of the transcriptional profile in
      nitrogen deficiency-a condition known to stimulate lipid accumulation. While the
      content of lipids increased, we did not detect major changes in expression of the
      genes involved in their biosynthesis. At the same time, we observed a very
      significant down-regulation of mitochondrial gene expression, suggesting that
      part of the Acetyl-CoA and NAD(P)H, normally oxidized through the mitochondrial
      respiration, would be made available for fatty acids synthesis, increasing the
      flux through the lipid biosynthetic pathway. Finally, we released an information
      resource of the genomic data of N. gaditana, available online at
      www.nannochloropsis.org.

PMID- 23966633
TI  - Human SAP is a novel peptidoglycan recognition protein that induces complement
      independent phagocytosis of Staphylococcus aureus.
AB  - The human pathogen Staphylococcus aureus is responsible for many community
      acquired and hospital-associated infections and is associated with high
      mortality. Concern over the emergence of multidrug-resistant strains has renewed
      interest in the elucidation of host mechanisms that defend against S. aureus
      infection. We recently demonstrated that human serum mannose-binding lectin binds
      to S. aureus wall teichoic acid (WTA), a cell wall glycopolymer--a discovery that
      prompted further screening to identify additional serum proteins that recognize
      S. aureus cell wall components. In this report, we incubated human serum with 10
      different S. aureus mutants and determined that serum amyloid P component (SAP)
      bound specifically to a WTA-deficient S. aureus DeltatagO mutant, but not to tagO
      complemented, WTA-expressing cells. Biochemical characterization revealed that
      SAP recognizes bacterial peptidoglycan as a ligand and that WTA inhibits this
      interaction. Although SAP binding to peptidoglycan was not observed to induce
      complement activation, SAP-bound DeltatagO cells were phagocytosed by human
      polymorphonuclear leukocytes in an FcgammaR-dependent manner. These results
      indicate that SAP functions as a host defense factor, similar to other
      peptidoglycan recognition proteins and nucleotide-binding oligomerization domain
      like receptors.

PMID- 23966635
TI  - Ongoing applicative studies of plant thioredoxins.
AB  - Studies triggered by the discovery of the function of thioredoxin (Trx) in
      photosynthesis have revealed its role throughout biology. Parallel biochemical
      and proteomic analyses have led to the identification of its numerous putative
      targets. Recently, to verify the biological significance of these targets, in
      vivo studies using transformants in which Trx is overexpressed or suppressed are
      in progress, and the transformants themselves that are being used in such studies
      show their potential applicative values. Moreover, Trx's mitigation of
      allergenicity for some proteins offers promising prospects in the food industry.
      Practical studies based on redox regulation, once only on the horizon, are now
      achieving new dimensions. This short review focuses on the industrial
      applications of Trx studies, the current situation, and future perspectives. The
      putative targets obtained by the proteomics approach in comparison with in vivo
      observations of the transformants are also examined. Applicative studies of
      glutathione, a counterpart of Trx, are also discussed briefly. 

PMID- 23966636
TI  - Genome-wide analysis of DNA methylation in soybean.
AB  - Cytosine methylation is an important mechanism for dynamical regulation of gene
      expression and transposable element (TE) mobility during plant developmental
      processes. Here, we identified the transcription start sites of genes using high
      throughput sequencing and then analyzed the DNA methylation status in soybean
      roots, stems, leaves, and cotyledons of developing seeds at single-base
      resolution. Profiling of DNA methylation in different organs revealed 2162
      differentially methylated regions among organs, and a portion of hypomethylated
      regions were correlated with high expression of neighboring genes. Because of the
      different distribution of class I TEs (retrotransposons) and class II TEs (DNA
      transposons), the promoters of the lowest-expressed genes showed higher levels of
      CG and CHG methylation but a lower level of CHH methylation. We further found
      that the CHH methylation level of class II TEs was higher than class I TEs,
      possibly due to the presence of more smRNAs in class II TEs. In cotyledons of
      developing seeds, smRNA abundance was roughly positively correlated with
      hypermethylated regions but negatively related to hypomethylated regions. These
      studies provide significant insights into the complicated interplays among DNA
      methylation, smRNA abundance, TE distribution, and gene expression in soybean. 

PMID- 23966637
TI  - Land-use change, not climate, controls organic carbon burial in lakes.
AB  - Lakes are a central component of the carbon cycle, both mineralizing
      terrestrially derived organic matter and storing substantial amounts of organic
      carbon (OC) in their sediments. However, the rates and controls on OC burial by
      lakes remain uncertain, as do the possible effects of future global change
      processes. To address these issues, we derived OC burial rates in (210)Pb-dated
      sediment cores from 116 small Minnesota lakes that cover major climate and land
      use gradients. Rates for individual lakes presently range from 7 to 127 g C m(-2)
      yr(-1) and have increased by up to a factor of 8 since Euro-American settlement
      (mean increase: 2.8*). Mean pre-disturbance OC burial rates were similar (14-22 g
      C m(-2) yr(-1)) across all land-cover categories (prairie, mixed deciduous and
      boreal forest), indicating minimal effect of the regional temperature gradient
      (approx. 4  degrees C) on background carbon burial. The relationship between
      modern OC burial rates and temperature was also not significant after removal of
      the effect of total phosphorus. Contemporary burial rates were strongly
      correlated with lake-water nutrients and the extent of agricultural land cover in
      the catchment. Increased OC burial, documented even in relatively undisturbed
      boreal lake ecosystems, indicates a possible role for atmospheric nitrogen
      deposition. Our results suggest that globally, future land-cover change,
      intensification of agriculture and associated nutrient loading together with
      atmospheric N-deposition will enhance OC sequestration by lakes.

PMID- 23966638
TI  - Anthropogenic environments exert variable selection on cranial capacity in
      mammals.
AB  - It is thought that behaviourally flexible species will be able to cope with novel
      and rapidly changing environments associated with human activity. However, it is
      unclear whether such environments are selecting for increases in behavioural
      plasticity, and whether some species show more pronounced evolutionary changes in
      plasticity. To test whether anthropogenic environments are selecting for
      increased behavioural plasticity within species, we measured variation in
      relative cranial capacity over time and space in 10 species of mammals. We
      predicted that urban populations would show greater cranial capacity than rural
      populations and that cranial capacity would increase over time in urban
      populations. Based on relevant theory, we also predicted that species capable of
      rapid population growth would show more pronounced evolutionary responses. We
      found that urban populations of two small mammal species had significantly
      greater cranial capacity than rural populations. In addition, species with higher
      fecundity showed more pronounced differentiation between urban and rural
      populations. Contrary to expectations, we found no increases in cranial capacity
      over time in urban populations-indeed, two species tended to have a decrease in
      cranial capacity over time in urban populations. Furthermore, rural populations
      of all insectivorous species measured showed significant increases in relative
      cranial capacity over time. Our results provide partial support for the
      hypothesis that urban environments select for increased behavioural plasticity,
      although this selection may be most pronounced early during the urban
      colonization process. Furthermore, these data also suggest that behavioural
      plasticity may be simultaneously favoured in rural environments, which are also
      changing because of human activity. 

PMID- 23966639
TI  - Parent--offspring similarity in the timing of developmental events: an origin of
      heterochrony?
AB  - Understanding the link between ontogeny (development) and phylogeny (evolution)
      remains a key aim of biology. Heterochrony, the altered timing of developmental
      events between ancestors and descendants, could be such a link although the
      processes responsible for producing heterochrony, widely viewed as an
      interspecific phenomenon, are still unclear. However, intraspecific variation in
      developmental event timing, if heritable, could provide the raw material from
      which heterochronies originate. To date, however, heritable developmental event
      timing has not been demonstrated, although recent work did suggest a genetic
      basis for intraspecific differences in event timing in the embryonic development
      of the pond snail, Radix balthica. Consequently, here we used high-resolution
      (temporal and spatial) imaging of the entire embryonic development of R. balthica
      to perform a parent-offspring comparison of the timing of twelve, physiological
      and morphological developmental events. Between-parent differences in the timing
      of all events were good predictors of such timing differences between their
      offspring, and heritability was demonstrated for two of these events (foot
      attachment and crawling). Such heritable intraspecific variation in developmental
      event timing could be the raw material for speciation events, providing a
      fundamental link between ontogeny and phylogeny, via heterochrony. 

PMID- 23966640
TI  - Persistent organic pollution in a high-Arctic top predator: sex-dependent
      thresholds in adult survival.
AB  - In long-lived species, any negative effect of pollution on adult survival may
      pose serious hazards to breeding populations. In this study, we measured
      concentrations of various organochlorines (OCs) (polychlorinated biphenyl and OC
      pesticides) in the blood of a large number of adult glaucous gulls (Larus
      hyperboreus) breeding on Bjornoya (Bear Island) in the Norwegian Arctic, and
      modelled their local survival using capture-recapture analysis. Survival was
      negatively associated with concentrations of OCs in the blood. The effect of OCs
      was nonlinear and evident only among birds with the highest concentrations (the
      uppermost deciles of contamination). The threshold for depressed survival
      differed between the sexes, with females being more sensitive to contamination.
      For birds with lower OC concentration, survival was very high, i.e. at the upper
      range of survival rates reported from glaucous and other large gull species in
      other, presumably less contaminated populations. We propose two non-exclusive
      explanations. First, at some threshold of OC concentration, parents (especially
      males) may abandon reproduction to maximize their own survival. Second, high
      contamination of OC may eliminate the most sensitive individuals from the
      population (especially among females), inducing a strong selection towards high
      quality and less sensitive phenotypes. 

PMID- 23966641
TI  - Endemic infection reduces transmission potential of an epidemic parasite during
      co-infection.
AB  - Endemic, low-virulence parasitic infections are common in nature. Such infections
      may deplete host resources, which in turn could affect the reproduction of other
      parasites during co-infection. We aimed to determine whether the reproduction,
      and therefore transmission potential, of an epidemic parasite was limited by
      energy costs imposed on the host by an endemic infection. Total lipids,
      triacylglycerols (TAG) and polar lipids were measured in cockroaches (Blattella
      germanica) that were fed ad libitum, starved or infected with an endemic
      parasite, Gregarina blattarum. Reproductive output of an epidemic parasite,
      Steinernema carpocapsae, was then assessed by counting the number of infective
      stages emerging from these three host groups. We found both starvation and
      gregarine infection reduced cockroach lipids, mainly through depletion of TAG.
      Further, both starvation and G. blattarum infection resulted in reduced emergence
      of nematode transmission stages. This is, to our knowledge, the first study to
      demonstrate directly that host resource depletion caused by endemic infection
      could affect epidemic disease transmission. In view of the ubiquity of endemic
      infections in nature, future studies of epidemic transmission should take greater
      account of endemic co-infections. 

PMID- 23966642
TI  - Invasive aquarium fish transform ecosystem nutrient dynamics.
AB  - Trade of ornamental aquatic species is a multi-billion dollar industry
      responsible for the introduction of myriad fishes into novel ecosystems. Although
      aquarium invaders have the potential to alter ecosystem function, regulation of
      the trade is minimal and little is known about the ecosystem-level consequences
      of invasion for all but a small number of aquarium species. Here, we demonstrate
      how ecological stoichiometry can be used as a framework to identify aquarium
      invaders with the potential to modify ecosystem processes. We show that explosive
      growth of an introduced population of stoichiometrically unique, phosphorus (P)
      rich catfish in a river in southern Mexico significantly transformed stream
      nutrient dynamics by altering nutrient storage and remineralization rates.
      Notably, changes varied between elements; the P-rich fish acted as net sinks of P
      and net remineralizers of nitrogen. Results from this study suggest species
      specific stoichiometry may be insightful for understanding how invasive species
      modify nutrient dynamics when their population densities and elemental
      composition differ substantially from native organisms. Risk analysis for
      potential aquarium imports should consider species traits such as body
      stoichiometry, which may increase the likelihood that an invasion will alter the
      structure and function of ecosystems. 

PMID- 23966643
TI  - Sexual selection explains more functional variation in the mammalian major
      histocompatibility complex than parasitism.
AB  - Understanding drivers of genetic diversity at the major histocompatibility
      complex (MHC) is vitally important for predicting how vertebrate immune defence
      might respond to future selection pressures and for preserving immunogenetic
      diversity in declining populations. Parasite-mediated selection is believed to be
      the major selective force generating MHC polymorphism, and while MHC-based mating
      preferences also exist for multiple species including humans, the general
      importance of mate choice is debated. To investigate the contributions of
      parasitism and sexual selection in explaining among-species variation in MHC
      diversity, we applied comparative methods and meta-analysis across 112 mammal
      species, including carnivores, bats, primates, rodents and ungulates. We tested
      whether MHC diversity increased with parasite richness and relative testes size
      (as an indicator of the potential for mate choice), while controlling for
      phylogenetic autocorrelation, neutral mutation rate and confounding ecological
      variables. We found that MHC nucleotide diversity increased with parasite
      richness for bats and ungulates but decreased with parasite richness for
      carnivores. By contrast, nucleotide diversity increased with relative testes size
      for all taxa. This study provides support for both parasite-mediated and sexual
      selection in shaping functional MHC polymorphism across mammals, and importantly,
      suggests that sexual selection could have a more general role than previously
      thought. 

PMID- 23966644
TI  - Backtracking behaviour in lost ants: an additional strategy in their navigational
      toolkit.
AB  - Ants use multiple sources of information to navigate, but do not integrate all
      this information into a unified representation of the world. Rather, the
      available information appears to serve three distinct main navigational systems:
      path integration, systematic search and the use of learnt information--mainly via
      vision. Here, we report on an additional behaviour that suggests a supplemental
      system in the ant's navigational toolkit: 'backtracking'. Homing ants, having
      almost reached their nest but, suddenly displaced to unfamiliar areas, did not
      show the characteristic undirected headings of systematic searches. Instead,
      these ants backtracked in the compass direction opposite to the path that they
      had just travelled. The ecological function of this behaviour is clear as we show
      it increases the chances of returning to familiar terrain. Importantly, the
      mechanistic implications of this behaviour stress an extra level of cognitive
      complexity in ant navigation. Our results imply: (i) the presence of a type of
      'memory of the current trip' allowing lost ants to take into account the familiar
      view recently experienced, and (ii) direct sharing of information across
      different navigational systems. We propose a revised architecture of the ant's
      navigational toolkit illustrating how the different systems may interact to
      produce adaptive behaviours.

PMID- 23966645
TI  - Stochastic environmental fluctuations drive epidemiology in experimental host
      parasite metapopulations.
AB  - Environmental fluctuations are important for parasite spread and persistence.
      However, the effects of the spatial and temporal structure of environmental
      fluctuations on host-parasite dynamics are not well understood. Temporal
      fluctuations can be random but positively autocorrelated, such that the
      environment is similar to the recent past (red noise), or random and uncorrelated
      with the past (white noise). We imposed red or white temporal temperature
      fluctuations on experimental metapopulations of Paramecium caudatum, experiencing
      an epidemic of the bacterial parasite Holospora undulata. Metapopulations (two
      subpopulations linked by migration) experienced fluctuations between stressful (5
      degrees C) and permissive (23  degrees C) conditions following red or white
      temporal sequences. Spatial variation in temperature fluctuations was implemented
      by exposing subpopulations to the same (synchronous temperatures) or different
      (asynchronous temperatures) temporal sequences. Red noise, compared with white
      noise, enhanced parasite persistence. Despite this, red noise coupled with
      asynchronous temperatures allowed infected host populations to maintain sizes
      equivalent to uninfected populations. It is likely that this occurs because
      subpopulations in permissive conditions rescue declining subpopulations in
      stressful conditions. We show how patterns of temporal and spatial environmental
      fluctuations can impact parasite spread and host population abundance. We
      conclude that accurate prediction of parasite epidemics may require realistic
      models of environmental noise.

PMID- 23966647
TI  - Wilcoxon-Mann-Whitney test used for data that are not normally distributed.

PMID- 23966646
TI  - The evolution of compliance in the human lateral mid-foot.
AB  - Fossil evidence for longitudinal arches in the foot is frequently used to
      constrain the origins of terrestrial bipedality in human ancestors. This approach
      rests on the prevailing concept that human feet are unique in functioning with a
      relatively stiff lateral mid-foot, lacking the significant flexion and high
      plantar pressures present in non-human apes. This paradigm has stood for more
      than 70 years but has yet to be tested objectively with quantitative data.
      Herein, we show that plantar pressure records with elevated lateral mid-foot
      pressures occur frequently in healthy, habitually shod humans, with magnitudes in
      some individuals approaching absolute maxima across the foot. Furthermore, the
      same astonishing pressure range is present in bonobos and the orangutan (the most
      arboreal great ape), yielding overlap with human pressures. Thus, while the mean
      tendency of habitual mechanics of the mid-foot in healthy humans is indeed
      consistent with the traditional concept of the lateral mid-foot as a relatively
      rigid or stabilized structure, it is clear that lateral arch stabilization in
      humans is not obligate and is often transient. These findings suggest a level of
      detachment between foot stiffness during gait and osteological structure, hence
      fossilized bone morphology by itself may only provide a crude indication of mid
      foot function in extinct hominins. Evidence for thick plantar tissues in
      Ardipithecus ramidus suggests that a human-like combination of active and passive
      modulation of foot compliance by soft tissues extends back into an arboreal
      context, supporting an arboreal origin of hominin bipedalism in compressive
      orthogrady. We propose that the musculoskeletal conformation of the modern human
      mid-foot evolved under selection for a functionally tuneable, rather than
      obligatory stiff structure. 

PMID- 23966648
TI  - Special article: basic perioperative transesophageal echocardiography
      examination: a consensus statement of the American Society of Echocardiography
      and the Society of Cardiovascular Anesthesiologists.

PMID- 23966649
TI  - The effect of sevoflurane on coronary flow reserve.

PMID- 23966650
TI  - Paucity of education regarding pacemakers/cardiovascular implantable electronic
      devices in anesthesiology training programs is a patient safety hazard.

PMID- 23966651
TI  - Intubation with a VivaSight single lumen through a supraglottic airway device.

PMID- 23966652
TI  - Standardization of extraglottic airway devices, is it time yet?

PMID- 23966653
TI  - Use of the American Society of Anesthesiologists Physical Status Classification
      System in research.

PMID- 23966657
TI  - T-cell immunophenotyping distinguishes active from latent tuberculosis.
AB  - BACKGROUND: Changes in the phenotype and function of Mycobacterium tuberculosis
      (M. tuberculosis)-specific CD4+ and CD8+ T-cell subsets in response to stage of
      infection may allow discrimination between active tuberculosis and latent
      tuberculosis infection. METHODS: A prospective comparison of M. tuberculosis
      specific cellular immunity in subjects with active tuberculosis and latent
      tuberculosis infection, with and without human immunodeficiency virus (HIV)
      coinfection. Polychromatic flow cytometry was used to measure CD4+ and CD8+ T
      cell subset phenotype and secretion of interferon gamma (IFN-gamma), interleukin
      2 (IL-2), and tumor necrosis factor alpha (TNF-alpha). RESULTS: Frequencies of
      CD4+ and CD8+ cells secreting IFN-gamma-only, TNF-alpha-only and dual IFN
      gamma/TNF-alpha were greater in active tuberculosis vs latent tuberculosis
      infection. All M. tuberculosis-specific CD4+ subsets, with the exception of IL-2
      only cells, switched from central to effector memory phenotype in active
      tuberculosis vs latent tuberculosis infection, accompanied by a reduction in IL-7
      receptor alpha (CD127) expression. The frequency of PPDspecific CD4+ TNF-alpha
      only-secreting T cells with an effector phenotype accurately distinguished active
      tuberculosis from latent tuberculosis infection with an area under the curve of
      0.99, substantially more discriminatory than measurement of function alone.
      CONCLUSIONS: Combined measurement of T-cell phenotype and function defines a
      highly discriminatory biomarker of tuberculosis disease activity. Unlocking the
      diagnostic and monitoring potential of this combined approach now requires
      validation in large-scale prospective studies.

PMID- 23966665
TI  - Erythropoietin administration partially prevents adipose tissue loss in
      experimental cancer cachexia models.
AB  - Cancer-associated cachexia is characterized, among other symptoms, by a dramatic
      loss of both muscle and fat. In addition, the cachectic syndrome is often
      associated with anemia. The object of the present investigation was to assess the
      effects of erythropoietin (EPO) treatment on experimental cancer cachexia models.
      The results clearly show that, in addition to the improvement of the hematocrit,
      EPO treatment promoted a partial preservation of adipose tissue while exerting
      negligible effects on muscle loss. Administration of EPO to tumor-bearing animals
      resulted in a significant increase of lipoprotein lipase (LPL) activity in
      adipose tissue, suggesting that the treatment favored triacylglycerol (TAG)
      accumulation in the adipose tissue. In vitro experiments using both adipose
      tissue slices and 3T3-L1 adipocytes suggests that EPO is able to increase the
      lipogenic rate through the activation of its specific receptor (EPOR). This
      metabolic pathway, in addition to TAG uptake by LPL, may contribute to the
      beneficial effects of EPO on fat preservation in cancer cachexia. 

PMID- 23966666
TI  - Statins stimulate the production of a soluble form of the receptor for advanced
      glycation end products.
AB  - The beneficial effects of statin therapy in the reduction of cardiovascular
      pathogenesis, atherosclerosis, and diabetic complications are well known. The
      receptor for advanced glycation end products (RAGE) plays an important role in
      the progression of these diseases. In contrast, soluble forms of RAGE act as
      decoys for RAGE ligands and may prevent the development of RAGE-mediated
      disorders. Soluble forms of RAGE are either produced by alternative splicing
      [endogenous secretory RAGE (esRAGE)] or by proteolytic shedding mediated by
      metalloproteinases [shed RAGE (sRAGE)]. Therefore we analyzed whether statins
      influence the production of soluble RAGE. Lovastatin treatment of either mouse
      alveolar epithelial cells endogenously expressing RAGE or HEK cells
      overexpressing RAGE caused induction of RAGE shedding, but did not influence
      secretion of esRAGE from HEK cells overexpressing esRAGE. Lovastatin-induced
      secretion of sRAGE was also evident after restoration of the isoprenylation
      pathway, demonstrating a correlation of sterol biosynthesis and activation of
      RAGE shedding. Lovastatin-stimulated induction of RAGE shedding was completely
      abolished by a metalloproteinase ADAM10 inhibitor. We also demonstrate that
      statins stimulate RAGE shedding at low physiologically relevant concentrations.
      Our results show that statins, due to their cholesterol-lowering effects,
      increase the soluble RAGE level by inducing RAGE shedding, and by doing this,
      might prevent the development of RAGE-mediated pathogenesis. 

PMID- 23966667
TI  - Preparation of 20-HETE using multifunctional enzyme type 2-negative Starmerella
      bombicola.
AB  - The metabolism of arachidonic acid (ARA) by cytochrome P450 omega/omega-1
      hydroxylases leads to the formation of 20-hydroxyeicosatetraenoic acid (20-HETE),
      which is an important lipid-signaling molecule involved in regulation of vascular
      tone, angiogenesis, and inflammation. Development of a simple method to prepare
      20-HETE would greatly facilitate the investigation of its biological activities.
      The nonpathogenic yeast Starmerella bombicola has been shown to convert
      exogenously added arachidonic acid to 20-HETE via the biosynthetic pathway of
      sophorolipids; however, the yield was low. Here we demonstrate that genetic
      knockout of multifunctional enzyme type 2 (MFE-2), which is involved in the beta
      oxidation of fatty acids, significantly increases the yield of ARA conversion to
      20-HETE and allows practical preparation of 20-HETE. 

PMID- 23966668
TI  - Reduced GABAergic inhibition of kidney-related PVN neurons in streptozotocin
      treated type 1 diabetic mouse.
AB  - Activity of presympathetic neurons in the paraventricular nucleus (PVN) of the
      hypothalamus is known to play an important role in the regulation of sympathetic
      outflow. Sympathetic overactivity is associated with many pathophysiological
      conditions such as diabetes mellitus and hypertension; however, the underlying
      synaptic mechanisms are poorly understood. In this study, we examined the
      GABAergic inhibitory synaptic control of kidney-related presympathetic PVN
      neurons in the streptozotocin-treated type 1 diabetic mouse model, using patch
      clamp slice electrophysiology in combination with retrograde labeling. Type 1
      diabetes resulted in decreased frequency of miniature inhibitory postsynaptic
      currents (mIPSCs). Our data also demonstrated a reduction of mIPSC amplitude and
      mean inhibitory current without alteration of input resistance. Furthermore, our
      data revealed decreased tonic GABAergic inhibition of kidney-related PVN neurons
      in diabetic conditions, which was consistent with the observed increased
      excitability of the presympathetic PVN neurons. In summary, our data demonstrated
      decreased phasic and tonic inhibitory control of kidney-related presympathetic
      PVN neurons that suggest altered sympathetic circuitry in type 1 diabetes. 

PMID- 23966669
TI  - alpha(5)GABA(A) receptors mediate primary afferent fiber tonic excitability in
      the turtle spinal cord.
AB  - gamma-Amino butyric acid (GABA) plays a key role in the regulation of central
      nervous system by activating synaptic and extrasynaptic GABAA receptors. It is
      acknowledged that extrasynaptic GABAA receptors located in the soma, dendrites,
      and axons may be activated tonically by low extracellular GABA concentrations.
      The activation of these receptors produces a persistent conductance that can
      hyperpolarize or depolarize nerve cells depending on the Cl(-) equilibrium
      potential. In an in vitro preparation of the turtle spinal cord we show that
      extrasynaptic alpha5GABAA receptors mediate the tonic state of excitability of
      primary afferents independently of the phasic primary afferent depolarization
      mediated by synaptic GABAA receptors. Blockade of alpha5GABAA receptors with the
      inverse agonist L-655,708 depressed the dorsal root reflex (DRR) without
      affecting the phasic increase in excitability of primary afferents. Using RT-PCR
      and Western blotting, we corroborated the presence of the mRNA and the
      alpha5GABAA protein in the dorsal root ganglia of the turtle spinal cord. The
      receptors were localized in primary afferents in dorsal root, dorsal root
      ganglia, and peripheral nerve terminals using immunoconfocal microscopy.
      Considering the implications of the DRR in neurogenic inflammation, alpha5GABAA
      receptors may serve as potential pharmacological targets for the treatment of
      pain. 

PMID- 23966670
TI  - Neuronal responses to target onset in oculomotor and somatomotor parietal
      circuits differ markedly in a choice task.
AB  - We often look at and sometimes reach for visible targets. Looking at a target is
      fast and relatively easy. By comparison, reaching for an object is slower and is
      associated with a larger cost. We hypothesized that, as a result of these
      differences, abrupt visual onsets may drive the circuits involved in saccade
      planning more directly and with less intermediate regulation than the circuits
      involved in reach planning. To test this hypothesis, we recorded discharge
      activity of neurons in the parietal oculomotor system (area LIP) and in the
      parietal somatomotor system (area PRR) while monkeys performed a visually guided
      movement task and a choice task. We found that in the visually guided movement
      task LIP neurons show a prominent transient response to target onset. PRR neurons
      also show a transient response, although this response is reduced in amplitude,
      is delayed, and has a slower rise time compared with LIP. A more striking
      difference is observed in the choice task. The transient response of PRR neurons
      is almost completely abolished and replaced with a slow buildup of activity,
      while the LIP response is merely delayed and reduced in amplitude. Our findings
      suggest that the oculomotor system is more closely and obligatorily coupled to
      the visual system, whereas the somatomotor system operates in a more
      discriminating manner. 

PMID- 23966671
TI  - Perceptual learning in sensorimotor adaptation.
AB  - Motor learning often involves situations in which the somatosensory targets of
      movement are, at least initially, poorly defined, as for example, in learning to
      speak or learning the feel of a proper tennis serve. Under these conditions,
      motor skill acquisition presumably requires perceptual as well as motor learning.
      That is, it engages both the progressive shaping of sensory targets and
      associated changes in motor performance. In the present study, we test the idea
      that perceptual learning alters somatosensory function and in so doing produces
      changes to human motor performance and sensorimotor adaptation. Subjects in these
      experiments undergo perceptual training in which a robotic device passively moves
      the subject's arm on one of a set of fan-shaped trajectories. Subjects are
      required to indicate whether the robot moved the limb to the right or the left
      and feedback is provided. Over the course of training both the perceptual
      boundary and acuity are altered. The perceptual learning is observed to improve
      both the rate and extent of learning in a subsequent sensorimotor adaptation task
      and the benefits persist for at least 24 h. The improvement in the present
      studies varies systematically with changes in perceptual acuity and is obtained
      regardless of whether the perceptual boundary shift serves to systematically
      increase or decrease error on subsequent movements. The beneficial effects of
      perceptual training are found to be substantially dependent on reinforced
      decision-making in the sensory domain. Passive-movement training on its own is
      less able to alter subsequent learning in the motor system. Overall, this study
      suggests perceptual learning plays an integral role in motor learning. 

PMID- 23966672
TI  - Detection of submillisecond spike timing differences based on delay-line
      anticoincidence detection.
AB  - Detection of submillisecond interaural timing differences is the basis for sound
      localization in reptiles, birds, and mammals. Although comparative studies reveal
      that different neural circuits underlie this ability, they also highlight common
      solutions to an inherent challenge: processing information on timescales shorter
      than an action potential. Discrimination of small timing differences is also
      important for species recognition during communication among mormyrid electric
      fishes. These fishes generate a species-specific electric organ discharge (EOD)
      that is encoded into submillisecond-to-millisecond timing differences between
      receptors. Small, adendritic neurons (small cells) in the midbrain are thought to
      analyze EOD waveform by comparing these differences in spike timing, but direct
      recordings from small cells have been technically challenging. In the present
      study we use a fluorescent labeling technique to obtain visually guided
      extracellular recordings from individual small cell axons. We demonstrate that
      small cells receive 1-2 excitatory inputs from 1 or more receptive fields with
      latencies that vary by over 10 ms. This wide range of excitatory latencies is
      likely due to axonal delay lines, as suggested by a previous anatomic study. We
      also show that inhibition of small cells from a calyx synapse shapes stimulus
      responses in two ways: through tonic inhibition that reduces spontaneous activity
      and through precisely timed, stimulus-driven, feed-forward inhibition. Our
      results reveal a novel delay-line anticoincidence detection mechanism for
      processing submillisecond timing differences, in which excitatory delay lines and
      precisely timed inhibition convert a temporal code into a population code. 

PMID- 23966674
TI  - Short- and long-term plasticity in CA1 neurons from mice lacking h-channel
      auxiliary subunit TRIP8b.
AB  - Hyperpolarization-activated cyclic nucleotide-gated nonselective cation channels
      (HCN or h-channels) are important regulators of neuronal physiology contributing
      to passive membrane properties, such as resting membrane potential and input
      resistance (R(N)), and to intrinsic oscillatory activity and synaptic
      integration. The correct membrane targeting of h-channels is regulated in part by
      the auxiliary h-channel protein TRIP8b. The genetic deletion of TRIP8b results in
      a loss of functional h-channels, which affects the postsynaptic integrative
      properties of neurons. We investigated the impact of TRIP8b deletion on long-term
      potentiation (LTP) at the two major excitatory inputs to CA1 pyramidal neurons:
      Schaffer collateral (SC) and perforant path (PP). We found that SC LTP was not
      significantly different between neurons from wild-type and TRIP8b-knockout mice.
      There was, however, significantly more short-term potentiation in knockout
      neurons. We also found that the persistent increase in h-current (I(h)) that
      normally occurs after LTP induction was absent in knockout neurons. The lack of
      I(h) plasticity was not restricted to activity-dependent induction, because the
      depletion of intracellular calcium stores also failed to produce the expected
      increase in I(h). Interestingly, pairing of SC and PP inputs resulted in a form
      of LTP in knockout neurons that did not occur in wild-type neurons. These results
      suggest that the physiological impact of TRIP8b deletion is not restricted to the
      integrative properties of neurons but also includes both synaptic and intrinsic
      plasticity.

PMID- 23966675
TI  - Spatiotemporal integration for tactile localization during arm movements: a
      probabilistic approach.
AB  - It has been shown that people make systematic errors in the localization of a
      brief tactile stimulus that is delivered to the index finger while they are
      making an arm movement. Here we modeled these spatial errors with a probabilistic
      approach, assuming that they follow from temporal uncertainty about the
      occurrence of the stimulus. In the model, this temporal uncertainty converts into
      a spatial likelihood about the external stimulus location, depending on arm
      velocity. We tested the prediction of the model that the localization errors
      depend on arm velocity. Participants (n = 8) were instructed to localize a
      tactile stimulus that was presented to their index finger while they were making
      either slow- or fast-targeted arm movements. Our results confirm the model's
      prediction that participants make larger localization errors when making faster
      arm movements. The model, which was used to fit the errors for both slow and fast
      arm movements simultaneously, accounted very well for all the characteristics of
      these data with temporal uncertainty in stimulus processing as the only free
      parameter. We conclude that spatial errors in dynamic tactile perception stem
      from the temporal precision with which tactile inputs are processed.

PMID- 23966673
TI  - Modulated discharge of Purkinje and stellate cells persists after unilateral loss
      of vestibular primary afferent mossy fibers in mice.
AB  - Cerebellar Purkinje cells are excited by two afferent pathways: climbing and
      mossy fibers. Climbing fibers evoke large "complex spikes" (CSs) that discharge
      at low frequencies. Mossy fibers synapse on granule cells whose parallel fibers
      excite Purkinje cells and may contribute to the genesis of "simple spikes" (SSs).
      Both afferent systems convey vestibular information to folia 9c-10. After making
      a unilateral labyrinthectomy (UL) in mice, we tested how the discharge of CSs and
      SSs was changed by the loss of primary vestibular afferent mossy fibers during
      sinusoidal roll tilt. We recorded from cells identified by juxtacellular
      neurobiotin labeling. The UL preferentially reduced vestibular modulation of CSs
      and SSs in folia 8-10 contralateral to the UL. The effects of a UL on Purkinje
      cell discharge were similar in folia 9c-10, to which vestibular primary afferents
      project, and in folia 8-9a, to which they do not project, suggesting that
      vestibular primary afferent mossy fibers were not responsible for the UL-induced
      alteration of SS discharge. UL also induced reduced vestibular modulation of
      stellate cell discharge contralateral to the UL. We attribute the decreased
      modulation to reduced vestibular modulation of climbing fibers. In summary,
      climbing fibers modulate CSs directly and SSs indirectly through activation of
      stellate cells. Whereas vestibular primary afferent mossy fibers cannot account
      for the modulated discharge of SSs or stellate cells, the nonspecific excitation
      of Purkinje cells by parallel fibers may set an operating point about which the
      discharges of SSs are sculpted by climbing fibers. 

PMID- 23966676
TI  - Regulation of dendritic calcium release in striatal spiny projection neurons.
AB  - The induction of corticostriatal long-term depression (LTD) in striatal spiny
      projection neurons (SPNs) requires coactivation of group I metabotropic glutamate
      receptors (mGluRs) and L-type Ca(2+) channels. This combination leads to the
      postsynaptic production of endocannabinoids that act presynaptically to reduce
      glutamate release. Although the necessity of coactivation is agreed upon, why it
      is necessary in physiologically meaningful settings is not. The studies described
      here attempt to answer this question by using two-photon laser scanning
      microscopy and patch-clamp electrophysiology to interrogate the dendritic
      synapses of SPNs in ex vivo brain slices from transgenic mice. These experiments
      revealed that postsynaptic action potentials induce robust ryanodine receptor
      (RYR)-dependent Ca(2+)-induced-Ca(2+) release (CICR) in SPN dendritic spines.
      Depolarization-induced opening of voltage-gated Ca(2+) channels was necessary for
      CICR. CICR was more robust in indirect pathway SPNs than in direct pathway SPNs,
      particularly in distal dendrites. Although it did not increase intracellular
      Ca(2+) concentration alone, group I mGluR activation enhanced CICR and slowed
      Ca(2+) clearance, extending the activity-evoked intraspine transient. The mGluR
      modulation of CICR was sensitive to antagonism of inositol trisphosphate
      receptors, RYRs, src kinase, and Cav1.3 L-type Ca(2+) channels. Uncaging
      glutamate at individual spines effectively activated mGluRs and facilitated CICR
      induced by back-propagating action potentials. Disrupting CICR by antagonizing
      RYRs prevented the induction of corticostriatal LTD with spike-timing protocols.
      In contrast, mGluRs had no effect on the induction of long-term potentiation.
      Taken together, these results make clearer how coactivation of mGluRs and L-type
      Ca(2+) channels promotes the induction of activity-dependent LTD in SPNs. 

PMID- 23966677
TI  - Weaker feedforward inhibition accounts for less pronounced thalamocortical
      response transformation in mouse vs. rat barrels.
AB  - Feedforward inhibition is a common motif of thalamocortical circuits. Strong
      engagement of inhibitory neurons by thalamic inputs enhances response
      differentials between preferred and nonpreferred stimuli. In rat whisker-barrel
      cortex, robustly driven inhibitory barrel neurons establish a brief epoch during
      which synchronous or near-synchronous thalamic firing produces larger responses
      to preferred stimuli, such as high-velocity deflections of the principal whisker
      in a preferred direction. Present experiments in mice show that barrel neuron
      responses to preferred vs. nonpreferred stimuli differ less than in rats. In
      addition, fast-spike units, thought to be inhibitory barrel neurons, fire less
      robustly to whisker stimuli in mice than in rats. Analyses of real and simulated
      data indicate that mouse barrel circuitry integrates thalamic inputs over a broad
      temporal window, and that, as a consequence, responses of barrel neurons are
      largely similar to those of thalamic neurons. Results are consistent with weaker
      feedforward inhibition in mouse barrels. Differences in thalamocortical circuitry
      between mice and rats may reflect mechanical properties of the whiskers
      themselves. 

PMID- 23966678
TI  - Unmasking the obligatory components of nociceptive event-related brain
      potentials.
AB  - It has been hypothesized that the human cortical responses to nociceptive and
      nonnociceptive somatosensory inputs differ. Supporting this view, somatosensory
      evoked potentials (SEPs) elicited by thermal nociceptive stimuli have been
      suggested to originate from areas 1 and 2 of the contralateral primary
      somatosensory (S1), operculo-insular, and cingulate cortices, whereas the early
      components of nonnociceptive SEPs mainly originate from area 3b of S1. However,
      to avoid producing a burn lesion, and sensitize or fatigue nociceptors,
      thermonociceptive SEPs are typically obtained by delivering a small number of
      stimuli with a large and variable interstimulus interval (ISI). In contrast, the
      early components of nonnociceptive SEPs are usually obtained by applying many
      stimuli at a rapid rate. Hence, previously reported differences between
      nociceptive and nonnociceptive SEPs could be due to differences in signal-to
      noise ratio and/or differences in the contribution of cognitive processes
      related, for example, to arousal and attention. Here, using intraepidermal
      electrical stimulation to selectively activate Adelta-nociceptors at a fast and
      constant 1-s ISI, we found that the nociceptive SEPs obtained with a long ISI are
      no longer identified, indicating that these responses are not obligatory for
      nociception. Furthermore, using a blind source separation, we found that, unlike
      the obligatory components of nonnociceptive SEPs, the obligatory components of
      nociceptive SEPs do not receive a significant contribution from a contralateral
      source possibly originating from S1. Instead, they were best explained by sources
      compatible with bilateral operculo-insular and/or cingulate locations. Taken
      together, our results indicate that the obligatory components of nociceptive and
      nonnociceptive SEPs are fundamentally different. 

PMID- 23966679
TI  - Spectral reconstruction of phase response curves reveals the synchronization
      properties of mouse globus pallidus neurons.
AB  - The propensity of a neuron to synchronize is captured by its infinitesimal phase
      response curve (iPRC). Determining whether an iPRC is biphasic, meaning that
      small depolarizing perturbations can actually delay the next spike, if delivered
      at appropriate phases, is a daunting experimental task because negative lobes in
      the iPRC (unlike positive ones) tend to be small and may be occluded by the
      normal discharge variability of a neuron. To circumvent this problem, iPRCs are
      commonly derived from numerical models of neurons. Here, we propose a novel and
      natural method to estimate the iPRC by direct estimation of its spectral modes.
      First, we show analytically that the spectral modes of the iPRC of an arbitrary
      oscillator are readily measured by applying weak harmonic perturbations. Next,
      applying this methodology to biophysical neuronal models, we show that a low
      dimensional spectral reconstruction is sufficient to capture the structure of the
      iPRC. This structure was preserved reasonably well even with added physiological
      scale jitter in the neuronal models. To validate the methodology empirically, we
      applied it first to a low-noise electronic oscillator with a known design and
      then to cortical pyramidal neurons, recorded in whole cell configuration, that
      are known to possess a monophasic iPRC. Finally, using the methodology in
      conjunction with perforated-patch recordings from pallidal neurons, we show, in
      contrast to recent modeling studies, that these neurons have biphasic somatic
      iPRCs. Biphasic iPRCs would cause lateral somatically targeted pallidal
      inhibition to desynchronize pallidal neurons, providing a plausible explanation
      for their lack of synchrony in vivo. 

PMID- 23966680
TI  - Effects of cerebellar lesions on working memory interacting with motor tasks of
      different complexities.
AB  - We examined the influence of focal cerebellar lesions on working memory (n-back
      task), gait, and the interaction between working memory and different gait tasks
      in a dual-task paradigm. The analysis included 17 young patients with chronic
      focal lesions after cerebellar tumor resection and 17 age-matched controls.
      Patients have shown mild to moderate ataxia. Lesion sites were examined on the
      basis of structural magnetic resonance imaging. N-back tasks were executed with
      different levels of difficulty (n = 1-4) during sitting (baseline), treadmill
      walking, and treadmill tandem walking (dual-task conditions). Patients exhibited
      decreased n-back performance particularly at difficult n-back levels and in dual
      task conditions. Voxel-based lesion-symptom mapping revealed that decreased
      baseline n-back performance was associated with lesions of the posterolateral
      cerebellar hemisphere and the dentate nucleus. By contrast, decreased n-back
      performance in dual-task conditions was more associated with motor-related areas
      including dorsal portions of the dentate and the interposed nucleus, suggesting a
      prioritization of the motor task. During baseline walking, increased gait
      variability was associated with lesions in medial and intermediate regions,
      whereas for baseline tandem gait, lesions in the posterolateral hemispheres and
      the dentate nucleus became important. Posterolateral regions overlapped with
      regions related to baseline n-back performance. Consistently, we observed
      increased tandem gait variability with growing n-back difficulty in the dual-task
      condition. These findings suggest that dual-task effects in cerebellar patients
      are at least partially caused by a common involvement of posterolateral
      cerebellar regions in working memory and complex motor tasks. 

PMID- 23966681
TI  - Neural mechanisms of social reorientation across adolescence.

PMID- 23966682
TI  - Prefrontal cortex HCN1 channels enable intrinsic persistent neural firing and
      executive memory function.
AB  - In many cortical neurons, HCN1 channels are the major contributors to Ih, the
      hyperpolarization-activated current, which regulates the intrinsic properties of
      neurons and shapes their integration of synaptic inputs, paces rhythmic activity,
      and regulates synaptic plasticity. Here, we examine the physiological role of Ih
      in deep layer pyramidal neurons in mouse prefrontal cortex (PFC), focusing on
      persistent activity, a form of sustained firing thought to be important for the
      behavioral function of the PFC during working memory tasks. We find that HCN1
      contributes to the intrinsic persistent firing that is induced by a brief
      depolarizing current stimulus in the presence of muscarinic agonists. Deletion of
      HCN1 or acute pharmacological blockade of Ih decreases the fraction of neurons
      capable of generating persistent firing. The reduction in persistent firing is
      caused by the membrane hyperpolarization that results from the deletion of HCN1
      or Ih blockade, rather than a specific role of the hyperpolarization-activated
      current in generating persistent activity. In vivo recordings show that deletion
      of HCN1 has no effect on up states, periods of enhanced synaptic network
      activity. Parallel behavioral studies demonstrate that HCN1 contributes to the
      PFC-dependent resolution of proactive interference during working memory. These
      results thus provide genetic evidence demonstrating the importance of HCN1 to
      intrinsic persistent firing and the behavioral output of the PFC. The causal role
      of intrinsic persistent firing in PFC-mediated behavior remains an open question.

PMID- 23966683
TI  - Prenatal exposure to nicotine stimulates neurogenesis of orexigenic peptide
      expressing neurons in hypothalamus and amygdala.
AB  - Animal and clinical studies show that gestational exposure to nicotine increases
      the propensity of offspring to consume nicotine, but the precise mechanism
      mediating this behavioral phenomenon is unclear. The present study in Sprague
      Dawley rats examined the possibility that the orexigenic peptide systems,
      enkephalin (ENK) and orexin (OX), which are stimulated by nicotine in adult
      animals and promote consummatory behavior, may be similarly responsive to
      nicotine's stimulatory effect in utero while having long-term behavioral
      consequences. The results demonstrated that nicotine exposure during gestation at
      low doses (0.75 or 1.5 mg/kg/d) significantly increased mRNA levels and density
      of neurons that express ENK in the hypothalamic paraventricular nucleus and
      central nucleus of the amygdala, OX, and another orexigenic peptide, melanin
      concentrating hormone, in the perifornical lateral hypothalamus in preweanling
      offspring. These effects persisted in the absence of nicotine, at least until
      puberty. Colabeling of the cell proliferation marker BrdU with the neuronal
      marker NeuN and peptides revealed a marked stimulatory effect of prenatal
      nicotine on neurogenesis, but not gliogenesis, and also on the number of newly
      generated neurons expressing ENK, OX, or melanin-concentrating hormone. During
      adolescence, offspring also exhibited significant behavioral changes, increased
      consumption of nicotine and other substances of abuse, ethanol and a fat-rich
      diet, with no changes in chow and water intake or body weight. These findings
      reveal a marked sensitivity during gestation of the orexigenic peptide neurons to
      low nicotine doses that may increase the offspring's propensity to overconsume
      substances of abuse during adolescence. 

PMID- 23966684
TI  - Systemic delivery of MeCP2 rescues behavioral and cellular deficits in female
      mouse models of Rett syndrome.
AB  - De novo mutations in the X-linked gene encoding the transcription factor methyl
      CpG binding protein 2 (MECP2) are the most frequent cause of the neurological
      disorder Rett syndrome (RTT). Hemizygous males usually die of neonatal
      encephalopathy. Heterozygous females survive into adulthood but exhibit severe
      symptoms including microcephaly, loss of purposeful hand motions and speech, and
      motor abnormalities, which appear after a period of apparently normal
      development. Most studies have focused on male mouse models because of the
      shorter latency to and severity in symptoms, yet how well these mice mimic the
      disease in affected females is not clear. Very few therapeutic treatments have
      been proposed for females, the more gender-appropriate model. Here, we show that
      self-complementary AAV9, bearing MeCP2 cDNA under control of a fragment of its
      own promoter (scAAV9/MeCP2), is capable of significantly stabilizing or reversing
      symptoms when administered systemically into female RTT mice. To our knowledge,
      this is the first potential gene therapy for females afflicted with RTT. 

PMID- 23966686
TI  - Involvement of the globus pallidus in behavioral goal determination and action
      specification.
AB  - Multiple loop circuits interconnect the basal ganglia and the frontal cortex, and
      each part of the cortico-basal ganglia loops plays an essential role in neuronal
      computational processes underlying motor behavior. To gain deeper insight into
      specific functions played by each component of the loops, we compared response
      properties of neurons in the globus pallidus (GP) with those in the dorsal
      premotor cortex (PMd) and the ventrolateral and dorsolateral prefrontal cortex
      (vlPFC and dlPFC) while monkeys performed a behavioral task designed to include
      separate processes for behavioral goal determination and action selection.
      Initially, visual signals instructed an abstract behavioral goal, and seconds
      later, a choice cue to select an action was presented. When the instruction cue
      appeared, GP neurons started to reflect visual features as early as vlPFC
      neurons. Subsequently, GP neurons began to reflect goals informed by the visual
      signals no later than neurons in the PMd, vlPFC, and dlPFC, indicating that the
      GP is involved in the early determination of behavioral goals. In contrast,
      action specification occurred later in the GP than in the cortical areas, and the
      GP was not as involved in the process by which a behavioral goal was transformed
      into an action. Furthermore, the length of time representing behavioral goal and
      action was shorter in the GP than in the PMd and dlPFC, indicating that the GP
      may play an important role in detecting individual behavioral events. These
      observations elucidate the involvement of the GP in goal-directed behavior. 

PMID- 23966685
TI  - Signals governing the trafficking and mistrafficking of a ciliary GPCR,
      rhodopsin.
AB  - Rhodopsin is a cilia-specific GPCR essential for vision. Rhodopsin
      mislocalization is associated with blinding diseases called retinal ciliopathies.
      The mechanism by which rhodopsin mislocalizes in rod photoreceptor neurons is not
      well understood. Therefore, we investigated the roles of trafficking signals in
      rhodopsin mislocalization. Rhodopsin and its truncation mutants were fused to a
      photoconvertible fluorescent protein, Dendra2, and expressed in Xenopus laevis
      rod photoreceptors. Photoconversion of Dendra2 causes a color change from green
      to red, enabling visualization of the dynamic events associated with rhodopsin
      trafficking and renewal. We found that rhodopsin mislocalization is a facilitated
      process for which a signal located within 322-326 aa (CCGKN) is essential. An
      additional signal within 327-336 aa further facilitated the mislocalization. This
      collective mistrafficking signal confers toxicity to rhodopsin and causes
      mislocalization when the VXPX cilia-targeting motif is absent. We also determined
      that the VXPX motif neutralizes this mistrafficking signal, enhances ciliary
      targeting at least 10-fold, and accelerates trafficking of post-Golgi vesicular
      structures. In the absence of the VXPX motif, mislocalized rhodopsin is actively
      cleared through secretion of vesicles into the extracellular milieu. Therefore,
      this study unveiled the multiple roles of trafficking signals in rhodopsin
      localization and renewal. 

PMID- 23966688
TI  - Dynamic neural network reorganization associated with second language vocabulary
      acquisition: a multimodal imaging study.
AB  - It remains unsettled whether human language relies exclusively on innately
      privileged brain structure in the left hemisphere or is more flexibly shaped
      through experiences, which induce neuroplastic changes in potentially relevant
      neural circuits. Here we show that learning of second language (L2) vocabulary
      and its cessation can induce bidirectional changes in the mirror-reverse of the
      traditional language areas. A cross-sectional study identified that gray matter
      volume in the inferior frontal gyrus pars opercularis (IFGop) and connectivity of
      the IFGop with the caudate nucleus and the superior temporal gyrus/supramarginal
      (STG/SMG), predominantly in the right hemisphere, were positively correlated with
      L2 vocabulary competence. We then implemented a cohort study involving 16 weeks
      of L2 training in university students. Brain structure before training did not
      predict the later gain in L2 ability. However, training intervention did increase
      IFGop volume and reorganization of white matter including the IFGop-caudate and
      IFGop-STG/SMG pathways in the right hemisphere. These "positive" plastic changes
      were correlated with the gain in L2 ability in the trained group but were not
      observed in the control group. We propose that the right hemispheric network can
      be reorganized into language-related areas through use-dependent plasticity in
      young adults, reflecting a repertoire of flexible reorganization of the neural
      substrates responding to linguistic experiences. 

PMID- 23966687
TI  - Optogenetic evidence that pallidal projections, not nigral projections, from the
      nucleus accumbens core are necessary for reinstating cocaine seeking.
AB  - The core subcompartment of the nucleus accumbens (NAcore) contributes
      significantly to behavioral responses following motivationally relevant stimuli,
      including drug-induced, stress-induced, and cue-induced reinstatement of cocaine
      seeking. Projections from NAcore that could carry information necessary to
      initiate reinstated cocaine seeking include outputs via the indirect pathway to
      the dorsolateral subcompartment of the ventral pallidum (dlVP) and through the
      direct pathway to the medial substantia nigra (SN). Here we used an optogenetic
      strategy to determine whether the dlVP or nigral projections from the NAcore are
      necessary for cocaine seeking initiated by a cocaine and conditioned cue
      combination in rats extinguished from cocaine self-administration. Rats were
      pretreated in the NAcore with an adeno-associated virus expressing the inhibitory
      opsin archaerhodopsin, and fiber-optic cannulae were implanted above the indirect
      pathway axon terminal field in the dlVP, or the direct pathway terminal field in
      the SN. Inhibiting the indirect pathway to the dlVP, but not the direct pathway
      to the SN, prevented cocaine-plus-cue-induced reinstatement. We also examined
      projections back to the NAcore from the ventral tegmental area (VTA) and dlVP.
      Inhibiting the dlVP to NAcore projection did not alter, while inhibiting VTA
      afferents abolished reinstated cocaine seeking. Localization of green fluorescent
      protein reporter expression and whole-cell patch electrophysiology were used to
      verify opsin expression. These data reveal a circuit involving activation of VTA
      inputs to the NAcore and NAcore projections through the indirect pathway to the
      dlVP as critical for cocaine-plus-cue-induced reinstatement of cocaine seeking. 

PMID- 23966689
TI  - Increased hippocampal neurogenesis and accelerated response to antidepressants in
      mice with specific deletion of CREB in the hippocampus: role of cAMP response
      element modulator tau.
AB  - The transcription factor cAMP response element-binding protein (CREB) has been
      implicated in the pathophysiology of depression as well as in the efficacy of
      antidepressant treatment. However, altering CREB levels appears to have differing
      effects on anxiety- and depression-related behaviors, depending on which brain
      region is examined. Furthermore, many manipulations of CREB lead to corresponding
      changes in other CREB family proteins, and the impact of these changes has been
      largely ignored. To further investigate the region-specific importance of CREB in
      depression-related behavior and antidepressant response, we used Creb(loxP/loxP)
      mice to localize CREB deletion to the hippocampus. In an assay sensitive to
      chronic antidepressant response, the novelty-induced hypophagia procedure,
      hippocampal CREB deletion, did not alter the response to chronic antidepressant
      treatment. In contrast, mice with hippocampal CREB deletion responded to acute
      antidepressant treatment in this task, and this accelerated response was
      accompanied by an increase in hippocampal neurogenesis. Upregulation of the CREB
      family protein cAMP response-element modulator (CREM) was observed after CREB
      deletion. Viral overexpression of the activator isoform of CREM, CREMtau, in the
      hippocampus also resulted in an accelerated response to antidepressants as well
      as increased hippocampal neurogenesis. This is the first demonstration of CREMtau
      within the brain playing a role in behavior and specifically in behavioral
      outcomes following antidepressant treatment. The current results suggest that
      activation of CREMtau may provide a means to accelerate the therapeutic efficacy
      of current antidepressant treatment. 

PMID- 23966690
TI  - Age-related cochlear synaptopathy: an early-onset contributor to auditory
      functional decline.
AB  - Aging listeners experience greater difficulty understanding speech in adverse
      listening conditions and exhibit degraded temporal resolution, even when
      audiometric thresholds are normal. When threshold evidence for peripheral
      involvement is lacking, central and cognitive factors are often cited as
      underlying performance declines. However, previous work has uncovered widespread
      loss of cochlear afferent synapses and progressive cochlear nerve degeneration in
      noise-exposed ears with recovered thresholds and no hair cell loss (Kujawa and
      Liberman 2009). Here, we characterize age-related cochlear synaptic and neural
      degeneration in CBA/CaJ mice never exposed to high-level noise. Cochlear hair
      cell and neuronal function was assessed via distortion product otoacoustic
      emissions and auditory brainstem responses, respectively. Immunostained cochlear
      whole mounts and plastic-embedded sections were studied by confocal and
      conventional light microscopy to quantify hair cells, cochlear neurons, and
      synaptic structures, i.e., presynaptic ribbons and postsynaptic glutamate
      receptors. Cochlear synaptic loss progresses from youth (4 weeks) to old age (144
      weeks) and is seen throughout the cochlea long before age-related changes in
      thresholds or hair cell counts. Cochlear nerve loss parallels the synaptic loss,
      after a delay of several months. Key functional clues to the synaptopathy are
      available in the neural response; these can be accessed noninvasively, enhancing
      the possibilities for translation to human clinical characterization. 

PMID- 23966691
TI  - X-linked intellectual disability-associated mutations in synaptophysin disrupt
      synaptobrevin II retrieval.
AB  - Synaptophysin is an integral synaptic vesicle (SV) protein that accounts for ~10%
      of total SV protein cargo. Deletion of synaptophysin results in the defective
      retrieval of synaptobrevin II (sybII) from the plasma membrane during
      endocytosis, coupled with a slowing in the speed of endocytosis. Synaptophysin
      has been implicated in X-linked intellectual disability, with a recent study
      identifying four separate synaptophysin gene mutations in families affected by
      the disorder. To determine how these mutations may affect synaptophysin function,
      we expressed them in cultured neurons derived from synaptophysin knock-out mice.
      Two distinct truncating mutants were mislocalized throughout the axon and
      phenocopied the arrest of sybII retrieval in synaptophysin knock-out cultures.
      The remaining two mutants displayed a nerve terminal localization but did not
      support efficient sybII retrieval. Interestingly, one mutant fully rescued SV
      endocytosis kinetics, suggesting that sybII retrieval and endocytosis speed are
      independent from each other. These studies suggest that the efficient retrieval
      of sybII by synaptophysin may be key to maintaining synaptic health and
      perturbation of this event may contribute to the pathogenesis underlying
      neurodevelopmental disorders such as X-linked intellectual disability. 

PMID- 23966692
TI  - Delusions and the role of beliefs in perceptual inference.
AB  - Delusions are unfounded yet tenacious beliefs and a symptom of psychotic
      disorder. Varying degrees of delusional ideation are also found in the healthy
      population. Here, we empirically validated a neurocognitive model that explains
      both the formation and the persistence of delusional beliefs in terms of altered
      perceptual inference. In a combined behavioral and functional neuroimaging study
      in healthy participants, we used ambiguous visual stimulation to probe the
      relationship between delusion-proneness and the effect of learned predictions on
      perception. Delusional ideation was associated with less perceptual stability,
      but a stronger belief-induced bias on perception, paralleled by enhanced
      functional connectivity between frontal areas that encoded beliefs and sensory
      areas that encoded perception. These findings suggest that weakened lower-level
      predictions that result in perceptual instability are implicated in the emergence
      of delusional beliefs. In contrast, stronger higher-level predictions that sculpt
      perception into conformity with beliefs might contribute to the tenacious
      persistence of delusional beliefs. 

PMID- 23966694
TI  - Dopamine regulates two classes of primate prefrontal neurons that represent
      sensory signals.
AB  - The lateral prefrontal cortex (PFC), a hub of higher-level cognitive processing,
      is strongly modulated by midbrain dopamine (DA) neurons. The cellular mechanisms
      have been comprehensively studied in the context of short-term memory, but little
      is known about how DA regulates sensory inputs to PFC that precede and give rise
      to such memory activity. By preparing recipient cortical circuits for incoming
      signals, DA could be a powerful determinant of downstream cognitive processing.
      Here, we tested the hypothesis that prefrontal DA regulates the representation of
      sensory signals that are required for perceptual decisions. In rhesus monkeys
      trained to report the presence or absence of visual stimuli at varying levels of
      contrast, we simultaneously recorded extracellular single-unit activity and
      applied DA to the immediate vicinity of the neurons by micro-iontophoresis. We
      found that DA modulation of prefrontal neurons is not uniform but tailored to
      specialized neuronal classes. In one population of neurons, DA suppressed
      activity with high temporal precision but preserved signal/noise ratio. Neurons
      in this group had short visual response latencies and comprised all recorded
      narrow-spiking, putative interneurons. In a distinct population, DA increased
      excitability and enhanced signal/noise ratio by reducing response variability.
      These neurons had longer visual response latencies and were composed exclusively
      of broad-spiking, putative pyramidal neurons. By gating sensory inputs to PFC and
      subsequently strengthening the representation of sensory signals, DA might play
      an important role in shaping how the PFC initiates appropriate behavior in
      response to changes in the sensory environment. 

PMID- 23966693
TI  - Parvalbumin-expressing inhibitory interneurons in auditory cortex are well-tuned
      for frequency.
AB  - In the auditory cortex, synaptic inhibition is known to be involved in shaping
      receptive fields, enhancing temporal precision, and regulating gain. Cortical
      inhibition is provided by local GABAergic interneurons, which comprise 10-20% of
      the cortical population and can be separated into numerous subclasses. The
      morphological and physiological diversity of interneurons suggests that these
      different subclasses have unique roles in sound processing; however, these roles
      are yet unknown. Understanding the receptive field properties of distinct
      inhibitory cell types will be critical to elucidating their computational
      function in cortical circuits. Here we characterized the tuning and response
      properties of parvalbumin-positive (PV+) interneurons, the largest inhibitory
      subclass. We used channelrhodopsin-2 (ChR2) as an optogenetic tag to identify PV+
      and PV- neurons in vivo in transgenic mice. In contrast to PV+ neurons in mouse
      visual cortex, which are broadly tuned for orientation, we found that auditory
      cortical PV+ neurons were well tuned for frequency, although very tightly tuned
      PV+ cells were uncommon. This suggests that PV+ neurons play a minor role in
      shaping frequency tuning, and is consistent with the idea that PV+ neurons
      nonselectively pool input from the local network. PV+ interneurons had shallower
      response gain and were less intensity-tuned than PV- neurons, suggesting that PV+
      neurons provide dynamic gain control and shape intensity tuning in auditory
      cortex. PV+ neurons also had markedly faster response latencies than PV- neurons,
      consistent with a computational role in enhancing the temporal precision of
      cortical responses. 

PMID- 23966695
TI  - Axonal localization of neuritin/CPG15 mRNA in neuronal populations through
      distinct 5' and 3' UTR elements.
AB  - Many neuronal mRNAs are actively transported into distal axons. The 3'
      untranslated regions (UTRs) of axonal mRNAs often contain cues for their
      localization. The 3' UTR of neuritin mRNA was shown to be sufficient for
      localization into axons of hippocampal neurons. Here, we show that neuritin mRNA
      localizes into axons of rat sensory neurons, but this is predominantly driven by
      the 5' rather than 3' UTR. Neuritin mRNA shifts from cell body to axon
      predominantly after nerve crush injury, suggesting that it encodes a growth
      associated protein. Consistent with this, overexpression of neuritin increases
      axon growth but only when its mRNA localizes into the axons. 

PMID- 23966697
TI  - Statistics of the electrosensory input in the freely swimming weakly electric
      fish Apteronotus leptorhynchus.
AB  - The neural computations underlying sensory-guided behaviors can best be
      understood in view of the sensory stimuli to be processed under natural
      conditions. This input is often actively shaped by the movements of the animal
      and its sensory receptors. Little is known about natural sensory scene statistics
      taking into account the concomitant movement of sensory receptors in freely
      moving animals. South American weakly electric fish use a self-generated quasi
      sinusoidal electric field for electrolocation and electrocommunication. Thousands
      of cutaneous electroreceptors detect changes in the transdermal potential (TDP)
      as the fish interact with conspecifics and the environment. Despite substantial
      knowledge about the circuitry and physiology of the electrosensory system, the
      statistical properties of the electrosensory input evoked by natural swimming
      movements have never been measured directly. Using underwater wireless telemetry,
      we recorded the TDP of Apteronotus leptorhynchus as they swam freely by
      themselves and during interaction with a conspecific. Swimming movements caused
      low-frequency TDP amplitude modulations (AMs). Interacting with a conspecific
      caused additional AMs around the difference frequency of their electric fields,
      with the amplitude of the AMs (envelope) varying at low frequencies due to mutual
      movements. Both AMs and envelopes showed a power-law relationship with frequency,
      indicating spectral scale invariance. Combining a computational model of the
      electric field with video tracking of movements, we show that specific swimming
      patterns cause characteristic spatiotemporal sensory input correlations that
      contain information that may be used by the brain to guide behavior. 

PMID- 23966698
TI  - Paired associative stimulation enforces the communication between interconnected
      areas.
AB  - Paired associative stimulation (PAS) protocols induce forms of spike-timing
      dependent-plasticity (STDP) when paired pulses are repeatedly applied with
      different timing over interconnected cortical areas such as the posterior
      parietal cortex (PPC) and the primary motor cortex (M1). However, the assessment
      of PAS effects is usually limited to M1 through recording of motor-evoked
      potential (MEP) amplitude. Here, by combining transcranial magnetic stimulation
      (TMS) with EEG we aimed at investigating PAS effects over both areas (PPC, M1)
      and the modulation induced on their connectivity in humans. In different PAS
      conditions, PPC preceded or followed M1 TMS by 5 ms. We found that TMS-evoked
      potentials (TEPs) changed differently according to the long-term depression (LTD)
      or potentiation (LTP) after-effect assessed by MEPs, but did not vary at PPC
      level. Moreover, there was no change in local oscillatory power. However, there
      was a remarkable increase of coherence between the PPC and the M1 areas. When the
      PAS protocol induced LTD as revealed by MEPs, there was a specific increase of
      the coherence between PPC and M1 within the beta band. On the contrary, when PAS
      induced LTP, the coherence crucially increased in the alpha band. The same LTP
      results were confirmed when rotating the stimulating coil in M1 during the PAS
      protocol. In conclusion, we report new evidence that opposite STDP-like effects
      induced by corticocortical PAS are associated with increased communication
      between involved brain areas and that antithetic forms of STDP-like after-effects
      result in distinct cortical rhythms connectivity changes. 

PMID- 23966696
TI  - CA1 pyramidal cell theta-burst firing triggers endocannabinoid-mediated long-term
      depression at both somatic and dendritic inhibitory synapses.
AB  - Endocannabinoids (eCBs) are retrograde lipid messengers that, by targeting
      presynaptic type 1 cannabinoid receptors (CB1Rs), mediate short- and long-term
      synaptic depression of neurotransmitter release throughout the brain. Short-term
      depression is typically triggered by postsynaptic, depolarization-induced calcium
      rises, whereas long-term depression is induced by synaptic activation of Gq/11
      protein-coupled receptors. Here we report that a physiologically relevant pattern
      of postsynaptic activity, in the form of theta-burst firing (TBF) of hippocampal
      CA1 pyramidal neurons, can trigger long-term depression of inhibitory
      transmission (iLTD) in rat hippocampal slices. Paired recordings between CA1
      interneurons and pyramidal cells, followed by post hoc morphological
      reconstructions of the interneurons' axon, revealed that somatic and dendritic
      inhibitory synaptic inputs equally expressed TBF-induced iLTD. Simultaneous
      recordings from neighboring pyramidal cells demonstrated that eCB signaling
      triggered by TBF was highly restricted to only a single, active cell.
      Furthermore, pairing submaximal endogenous activation of metabotropic glutamate
      or muscarinic acetylcholine receptors with submaximal TBF unmasked associative
      iLTD. Although CB1Rs are also expressed at Schaffer-collateral excitatory
      terminals, long-term plasticity under various recording conditions was spared at
      these synapses. Consistent with this observation, TBF also shifted the balance of
      excitation and inhibition in favor of excitatory throughput, thereby altering
      information flow through the CA1 circuit. Given the near ubiquity of burst-firing
      activity patterns and CB1R expression in the brain, the properties described here
      may be a general means by which neurons fine tune the strength of their inputs in
      a cell-wide and cell-specific manner. 

PMID- 23966699
TI  - Facilitation of pain in the human spinal cord by nocebo treatment.
AB  - Nocebo hyperalgesia is an increase in subjective pain perception after a patient
      or subject underwent an inert treatment without any active ingredient. For
      example, verbal suggestion of increased pain can enhance both pain experience and
      responses in pain-related cortical brain areas. However, changes in cortical pain
      responses may be secondary to earlier amplification of incoming pain signals
      within the spinal cord. To test for a potential early enhancement of pain signals
      in the dorsal horn of the spinal cord, we combined a nocebo heat pain paradigm
      with spinal functional magnetic resonance imaging in healthy volunteers. We found
      that local application of an inert nocebo cream on the forearm increased pain
      ratings compared with a control cream, and also reduced pain thresholds on the
      nocebo-treated skin patch. On the neurobiological level, pain stimulation induced
      a strong activation in the spinal cord at the level of the stimulated dermatomes
      C5/C6. Comparing pain stimulation under nocebo to a control pain stimulation of
      the same physical intensity revealed enhanced pain-related activity in the
      ipsilateral dorsal horn of the spinal cord. Importantly, the activation of the
      main effect of pain and the nocebo effect spatially overlapped. The current study
      thus provides direct evidence for a pain-facilitating mechanism in the human
      spinal cord before cortical processing, which can be activated by cognitive
      manipulations such as nocebo treatments. 

PMID- 23966701
TI  - Target-specific vulnerability of excitatory synapses leads to deficits in
      associative memory in a model of intellectual disorder.
AB  - Intellectual disorders (IDs) have been regularly associated with morphological
      and functional deficits at glutamatergic synapses in both humans and rodents. How
      these synaptic deficits may lead to the variety of learning and memory deficits
      defining ID is still unknown. Here we studied the functional and behavioral
      consequences of the ID gene il1rapl1 deficiency in mice and reported that
      il1rapl1 constitutive deletion alters cued fear memory formation. Combined in
      vivo and in vitro approaches allowed us to unveil a causal relationship between a
      marked inhibitory/excitatory (I/E) imbalance in dedicated amygdala neuronal
      subcircuits and behavioral deficits. Cell-targeted recordings further
      demonstrated a morpho-functional impact of the mutation at thalamic projections
      contacting principal cells, whereas the same afferents on interneurons are
      unaffected by the lack of Il1rapl1. We thus propose that excitatory synapses have
      a heterogeneous vulnerability to il1rapl1 gene constitutive mutation and that
      alteration of a subset of excitatory synapses in neuronal circuits is sufficient
      to generate permanent cognitive deficits. 

PMID- 23966700
TI  - MHCI requires MEF2 transcription factors to negatively regulate synapse density
      during development and in disease.
AB  - Major histocompatibility complex class I (MHCI) molecules negatively regulate
      cortical connections and are implicated in neurodevelopmental disorders,
      including autism spectrum disorders and schizophrenia. However, the mechanisms
      that mediate these effects are unknown. Here, we report a novel MHCI signaling
      pathway that requires the myocyte enhancer factor 2 (MEF2) transcription factors.
      In young rat cortical neurons, MHCI regulates MEF2 in an activity-dependent
      manner and requires calcineurin-mediated activation of MEF2 to limit synapse
      density. Manipulating MEF2 alone alters synaptic strength and GluA1 content, but
      not synapse density, implicating activity-dependent MEF2 activation as critical
      for MHCI signaling. The MHCI-MEF2 pathway identified here also mediates the
      effects of a mouse model of maternal immune activation (MIA) on connectivity in
      offspring. MHCI and MEF2 levels are higher, and synapse density is lower, on
      neurons from MIA offspring. Most important, dysregulation of MHCI and MEF2 is
      required for the MIA-induced reduction in neural connectivity. These results
      identify a previously unknown MHCI-calcineurin-MEF2 signaling pathway that
      regulates the establishment of cortical connections and mediates synaptic defects
      caused by MIA, a risk factor for autism spectrum disorders and schizophrenia. 

PMID- 23966703
TI  - Neural correlates of interval timing in rodent prefrontal cortex.
AB  - Time interval estimation is involved in numerous behavioral processes, but its
      underlying neural mechanisms remain unclear. In particular, it has been
      controversial whether time is encoded on a linear or logarithmic scale. Based on
      our previous finding that inactivation of the medial prefrontal cortex (mPFC)
      profoundly impairs rat's ability to discriminate time intervals, we investigated
      how the mPFC processes temporal information by examining activity of mPFC neurons
      in rats performing a temporal bisection task. Many mPFC neurons conveyed temporal
      information based on monotonically changing activity profiles over time with
      negative accelerations, so that their activity profiles were better described by
      logarithmic than linear functions. Moreover, the precision of time-interval
      discrimination based on neural activity was lowered in proportion to the elapse
      of time, but without proportional increase in neural variability, which is well
      accounted for by logarithmic, but not by linear functions. As a population, mPFC
      neurons conveyed precise information about the elapse of time with their activity
      tightly correlated with the animal's choice of target. These results suggest that
      the mPFC might be part of an internal clock in charge of controlling interval
      timing behavior, and that linearly changing neuronal activity on a logarithmic
      time scale might be one way of representing the elapse of time in the brain. 

PMID- 23966702
TI  - Stress-induced recruitment of bone marrow-derived monocytes to the brain promotes
      anxiety-like behavior.
AB  - Social stress is associated with altered immunity and higher incidence of anxiety
      related disorders. Repeated social defeat (RSD) is a murine stressor that primes
      peripheral myeloid cells, activates microglia, and induces anxiety-like behavior.
      Here we show that RSD-induced anxiety-like behavior corresponded with an exposure
      dependent increase in circulating monocytes (CD11b(+)/SSC(lo)/Ly6C(hi)) and brain
      macrophages (CD11b(+)/SSC(lo)/CD45(hi)). Moreover, RSD-induced anxiety-like
      behavior corresponded with brain region-dependent cytokine and chemokine
      responses involved with myeloid cell recruitment. Next, LysM-GFP(+) and GFP(+)
      bone marrow (BM)-chimeric mice were used to determine the neuroanatomical
      distribution of peripheral myeloid cells recruited to the brain during RSD. LysM
      GFP(+) mice showed that RSD increased recruitment of GFP(+) macrophages to the
      brain and increased their presence within the perivascular space (PVS). In
      addition, RSD promoted recruitment of GFP(+) macrophages into the PVS and
      parenchyma of the prefrontal cortex, amygdala, and hippocampus of GFP(+) BM
      chimeric mice. Furthermore, mice deficient in chemokine receptors associated with
      monocyte trafficking [chemokine receptor-2 knockout (CCR2(KO)) or fractalkine
      receptor knockout (CX3CR1(KO))] failed to recruit macrophages to the brain and
      did not develop anxiety-like behavior following RSD. Last, RSD-induced macrophage
      trafficking was prevented in BM-chimeric mice generated with CCR2(KO) or
      CX3CR1(KO) donor cells. These findings indicate that monocyte recruitment to the
      brain in response to social stress represents a novel cellular mechanism that
      contributes to the development of anxiety. 

PMID- 23966704
TI  - The ventral striato-pallidal pathway mediates the effect of predictive learning
      on choice between goal-directed actions.
AB  - The nucleus accumbens shell (NAc-S) plays an important role in the way stimuli
      that predict reward affect the performance of, and choice between, goal-directed
      actions in tests of outcome-specific Pavlovian-instrumental transfer (PIT). The
      neural processes involved in PIT downstream of the ventral striatum are, however,
      unknown. The NAc-S projects prominently to the ventral pallidum (VP), and in the
      current experiments, we assessed the involvement of the NAc-S to VP projection in
      specific PIT in rats. We first compared expression of the immediate-early gene c
      Fos in the medial (VP-m) and lateral (VP-l) regions of the VP and in addition,
      used the retrograde tracer Fluoro-gold combined with c-Fos to assess the
      involvement of these pathways during PIT. Although there was no evidence of
      differential activation in neurons in the VP-l, the VP-m showed a selective
      increase in activity in rats tested for PIT compared with appropriate controls,
      as did NAc-S neurons projecting to the VP-m. To confirm that VP-m activity is
      important for PIT, we inactivated this region before test and found this
      inactivation blocked the influence of predictive learning on choice. Finally, to
      confirm the functional importance of the NAc-S to VP-m pathway we used a
      disconnection procedure, using asymmetrical inactivation of the NAc-S and either
      the ipsilateral or contralateral VP-m. Specific PIT was blocked but only by
      inactivation of the NAc-S and VP-m in contralateral hemispheres. These results
      suggest that the NAc-S and VP-m form part of a circuit mediating the effects of
      predictive learning on choice. 

PMID- 23966706
TI  - Encoding and representation of intranasal CO2 in the mouse olfactory cortex.
AB  - Intranasal trigeminal sensory input, often perceived as a burning, tingling, or
      stinging sensation, is well known to affect odor perception. While both
      anatomical and functional imaging data suggest that the influence of trigeminal
      stimuli on odor information processing may occur within the olfactory cortex,
      direct electrophysiological evidence for the encoding of trigeminal information
      at this level of processing is unavailable. Here, in agreement with human
      functional imaging studies, we found that 26% of neurons in the mouse piriform
      cortex (PCX) display modulation in firing to carbon dioxide (CO2), an odorless
      stimulant with known trigeminal capacity. Interestingly, CO2 was represented
      within the PCX by distinct temporal dynamics, differing from those evoked by
      odor. Experiments with ascending concentrations of isopentyl acetate, an odorant
      known to elicit both olfactory and trigeminal sensations, resulted in morphing of
      the temporal dynamics of stimulus-evoked responses. Whereas low concentrations of
      odorant evoked responses upon stimulus onset, high concentrations of odorant
      and/or CO2 often evoked responses structured to stimulus offset. These
      physiological experiments in mice suggest that PCX neurons possess the capacity
      to encode for stimulus modality (olfactory vs trigeminal) by differential
      patterns of firing. These data provide mechanistic insights into the influences
      of trigeminal information on odor processing and place constraints on models of
      olfactory-trigeminal sensory integration. 

PMID- 23966705
TI  - Food restriction increases glutamate receptor-mediated burst firing of dopamine
      neurons.
AB  - Restriction of food intake increases the acquisition of drug abuse behavior and
      enhances the reinforcing efficacy of those drugs. However, the neurophysiological
      mechanisms responsible for the interactions between feeding state and drug use
      are largely unknown. Here we show that chronic mild food restriction increases
      the burst firing of dopamine neurons in the substantia nigra. Dopamine neurons
      from food-restricted mice exhibited increased burst firing in vivo, an effect
      that was enhanced by an injection of the psychomotor stimulant cocaine (10 mg/kg,
      i.p.). Food restriction also enhanced aspartic acid-induced burst firing of
      dopamine neurons in an ex vivo brain slice preparation, consistent with an
      adaptation occurring in the somatodendritic compartment and independent of a
      circuit mechanism. Enhanced burst firing persisted after 10 d of free feeding
      following chronic food restriction but was not observed following a single
      overnight fast. Whole-cell patch-clamp recordings indicated that food restriction
      also increased electrically evoked AMPAR/NMDAR ratios and increased D2
      autoreceptor-mediated desensitization in dopamine neurons. These results identify
      dopamine neurons in the substantia nigra as a convergence point for the
      interactions between feeding state and drugs of abuse. Furthermore, increased
      glutamate transmission combined with decreased autoreceptor inhibition could work
      in concert to enhance drug efficacy in response to food restriction. 

PMID- 23966708
TI  - Critical role of the hippocampus in memory for elapsed time.
AB  - Episodic memory includes information about how long ago specific events occurred.
      Since most of our experiences have overlapping elements, remembering this
      temporal context is crucial for distinguishing individual episodes. The discovery
      of timing signals in hippocampal neurons, including evidence of "time cells" and
      of gradual changes in ensemble activity over long timescales, strongly suggests
      that the hippocampus is important for this capacity. However, behavioral evidence
      that the hippocampus is critical for the memory of elapsed time is lacking. This
      is possibly because previous studies have used time durations in the range of
      seconds when assessing hippocampal dependence, a timescale known to require
      corticostriatal circuits. Here we developed a nonspatial paradigm to test the
      hypothesis that the hippocampus is critical for keeping track of elapsed time
      over several minutes. We report that rats have a robust ability to remember
      durations at this timescale. We then determined the role of the hippocampus using
      infusions of fluorophore-conjugated muscimol, a GABAA agonist. We found that the
      hippocampus was essential for discriminating smaller, but not larger, temporal
      differences (measured in log units), consistent with a role in temporal pattern
      separation. Importantly, this effect was observed at long (minutes) but not short
      (seconds) timescales, suggesting an interplay of temporal resolution and
      timescale in determining hippocampal dependence. These results offer compelling
      evidence that the hippocampus plays a critical role in remembering how long ago
      events occurred. 

PMID- 23966707
TI  - Perivascular fibroblasts form the fibrotic scar after contusive spinal cord
      injury.
AB  - Injury to the CNS leads to formation of scar tissue, which is important in
      sealing the lesion and inhibiting axon regeneration. The fibrotic scar that
      comprises a dense extracellular matrix is thought to originate from meningeal
      cells surrounding the CNS. However, using transgenic mice, we demonstrate that
      perivascular collagen1alpha1 cells are the main source of the cellular
      composition of the fibrotic scar after contusive spinal cord injury in which the
      dura remains intact. Using genetic lineage tracing, light sheet fluorescent
      microscopy, and antigenic profiling, we identify collagen1alpha1 cells as
      perivascular fibroblasts that are distinct from pericytes. Our results identify
      collagen1alpha1 cells as a novel source of the fibrotic scar after spinal cord
      injury and shift the focus from the meninges to the vasculature during scar
      formation. 

PMID- 23966710
TI  - Reliable sex and strain discrimination in the mouse vomeronasal organ and
      accessory olfactory bulb.
AB  - Animals modulate their courtship and territorial behaviors in response to
      olfactory cues produced by other animals. In rodents, detecting these cues is the
      primary role of the accessory olfactory system (AOS). We sought to systematically
      investigate the natural stimulus coding logic and robustness in neurons of the
      first two stages of accessory olfactory processing, the vomeronasal organ (VNO)
      and accessory olfactory bulb (AOB). We show that firing rate responses of just a
      few well-chosen mouse VNO or AOB neurons can be used to reliably encode both sex
      and strain of other mice from cues contained in urine. Additionally, we show that
      this population code can generalize to new concentrations of stimuli and appears
      to represent stimulus identity in terms of diverging paths in coding space.
      Together, the results indicate that firing rate code on the temporal order of
      seconds is sufficient for accurate classification of pheromonal patterns at
      different concentrations and may be used by AOS neural circuitry to discriminate
      among naturally occurring urine stimuli. 

PMID- 23966709
TI  - Enhanced spontaneous oscillations in the supplementary motor area are associated
      with sleep-dependent offline learning of finger-tapping motor-sequence task.
AB  - Sleep is beneficial for various types of learning and memory, including a finger
      tapping motor-sequence task. However, methodological issues hinder clarification
      of the crucial cortical regions for sleep-dependent consolidation in motor
      sequence learning. Here, to investigate the core cortical region for sleep
      dependent consolidation of finger-tapping motor-sequence learning, while human
      subjects were asleep, we measured spontaneous cortical oscillations by
      magnetoencephalography together with polysomnography, and source-localized the
      origins of oscillations using individual anatomical brain information from MRI.
      First, we confirmed that performance of the task at a retest session after sleep
      significantly increased compared with performance at the training session before
      sleep. Second, spontaneous delta and fast-sigma oscillations significantly
      increased in the supplementary motor area (SMA) during post-training compared
      with pretraining sleep, showing significant and high correlation with the
      performance increase. Third, the increased spontaneous oscillations in the SMA
      correlated with performance improvement were specific to slow-wave sleep. We also
      found that correlations of delta oscillation between the SMA and the prefrontal
      and between the SMA and the parietal regions tended to decrease after training.
      These results suggest that a core brain region for sleep-dependent consolidation
      of the finger-tapping motor-sequence learning resides in the SMA contralateral to
      the trained hand and is mediated by spontaneous delta and fast-sigma
      oscillations, especially during slow-wave sleep. The consolidation may arise
      along with possible reorganization of a larger-scale cortical network that
      involves the SMA and cortical regions outside the motor regions, including
      prefrontal and parietal regions. 

PMID- 23966711
TI  - Dopaminergic control of long-term depression/long-term potentiation threshold in
      prefrontal cortex.
AB  - Long-term memory in the prefrontal cortex is a necessary component of adaptive
      executive control and is strongly modulated by dopamine. However, the functional
      significance of this dopaminergic modulation remains elusive. In vitro
      experimental results on dopamine-dependent shaping of prefrontal long-term
      plasticity often appear inconsistent and, altogether, draw a complicated picture.
      It is also generally difficult to relate these findings to in vivo observations
      given strong differences between the two experimental conditions. This study
      presents a unified view of the functional role of dopamine in the prefrontal
      cortex by framing it within the Bienenstock-Cooper-Munro theory of cortical
      plasticity. We investigate dopaminergic modulation of long-term plasticity
      through a multicompartment Hodgkin-Huxley model of a prefrontal pyramidal neuron.
      Long-term synaptic plasticity in the model is governed by a calcium- and dopamine
      dependent learning rule, in which dopamine exerts its action via D1 and D2
      dopamine receptors in a concentration-dependent manner. Our results support a
      novel function of dopamine in the prefrontal cortex, namely that it controls the
      synaptic modification threshold between long-term depression and potentiation in
      pyramidal neurons. The proposed theoretical framework explains a wide range of
      experimental results and provides a link between in vitro and in vivo studies of
      dopaminergic plasticity modulation. It also suggests that dopamine may constitute
      a new player in metaplastic and homeostatic processes in the prefrontal cortex. 

PMID- 23966714
TI  - Oversupply and under-resourced: the global context of pharmacy education.

PMID- 23966712
TI  - Optogenetic control of fly optomotor responses.
AB  - When confronted with a large-field stimulus rotating around the vertical body
      axis, flies display a following behavior called "optomotor response." As neural
      control elements, the large tangential horizontal system (HS) cells of the lobula
      plate have been prime candidates for long. Here, we applied optogenetic
      stimulation of HS cells to evaluate their behavioral role in Drosophila. To
      minimize interference of the optical activation of channelrhodopsin-2 with the
      visual perception of the flies, we used a bistable variant called ChR2-C128S. By
      applying pulses of blue and yellow light, we first demonstrate
      electrophysiologically that lobula plate tangential cells can be activated and
      deactivated repeatedly with no evident change in depolarization strength over
      trials. We next show that selective optogenetic activation of HS cells elicits
      robust yaw head movements and yaw turning responses in fixed and tethered flying
      flies, respectively. 

PMID- 23966715
TI  - A need to rethink and mold consensus regarding pharmacy education in developing
      countries.

PMID- 23966716
TI  - Health information technology: are we aware and engaged?

PMID- 23966717
TI  - Pharmacy education in Vietnam.
AB  - Pharmacy education programs in Vietnam are complex and offer various career
      pathways. All include theory and laboratory modules in general, foundation, and
      pharmaceutical knowledge; placements in health facilities; and a final
      examination. The various pharmacy degree programs allow specialization in 1 or
      more of 5 main fields: (1) drug management and supply, (2) drug development and
      production, (3) pharmacology and clinical pharmacy, (4) traditional medicine and
      pharmacognosy, and (5) drug quality control, which are offered as main
      specialization options during the reformed undergraduate and postgraduate
      programs. However, pharmacy education in Vietnam in general remains product
      oriented and clinical pharmacy training has not received adequate attention. Only
      students who have obtained the bachelor of pharmacy degree, which requires a
      minimum of 5 years of study, are considered as fully qualified pharmacists. In
      contrast, an elementary diploma in pharmacy awarded after 1 year of pharmacy
      study permits entry into more junior pharmacy positions. Since the 2000s, there
      has been a surge in the number and types of schools offering pharmacy
      qualifications at various levels. 

PMID- 23966718
TI  - Team-based learning in US colleges and schools of pharmacy.
AB  - OBJECTIVE: To characterize the use of team-based learning (TBL) in US colleges
      and schools of pharmacy, including factors that may affect implementation and
      perceptions of faculty members regarding the impact of TBL on educational
      outcomes. METHODS: Respondents identified factors that inhibit or enable TBL use
      and its impact on student learning. Results were stratified by type of
      institution (public/private), class size, and TBL experience. RESULTS: Sixty-nine
      of 100 faculty members (69%) representing 43 (86%) institutions responded. Major
      factors considered to enable TBL implementation included a single campus and
      student and administration buy-in. Inhibiting factors included distant campuses,
      faculty resistance, and lack of training. Compared with traditional lectures, TBL
      is perceived to enhance student engagement, improve students' preparation for
      class, and promote achievement of course outcomes. In addition, TBL is perceived
      to be more effective than lectures at fostering learning in all 6 domains of
      Bloom's Taxonomy. CONCLUSIONS: Despite potential implementation challenges,
      faculty members perceive that TBL improves student engagement and learning.

PMID- 23966719
TI  - The prevalence and characteristics of dual PharmD/MPH programs offered at US
      colleges and schools of pharmacy.
AB  - OBJECTIVE: To assess the prevalence and characteristics of curriculum in dual
      doctor of pharmacy (PharmD)/master of public health (MPH) degree programs offered
      by US pharmacy programs. METHODS: An 18-item survey instrument was developed and
      distributed online to faculty members at US colleges and schools of pharmacy.
      RESULTS: Of the 110 colleges and schools that responded, 23 (21%) offered a
      PharmD/MPH degree. Common characteristics of these 23 programs included current
      PharmD program structure (3 + 1 year), early curricular recruitment, small
      enrollment, and interdisciplinary coursework occurring online and in the
      classroom. The impact of the dual degree on the curriculum and longevity of the
      dual-degree programs varied. About 55% of responding programs without a formal
      dual-degree program reported that additional public health training was
      available. CONCLUSION: Twenty-one percent of colleges and schools of pharmacy
      offer a combined PharmD/MPH dual degree. Most programs required an additional 1
      or 2 semesters to complete both degrees.

PMID- 23966720
TI  - A continuous quality improvement program to focus a college of pharmacy on
      programmatic advancement.
AB  - OBJECTIVE: To enhance the achievement of a college of pharmacy's goals for
      education, research, and service missions by implementing an excellence program
      based on the Studer Group model for continuous quality improvement. METHODS: The
      Studer model was combined with university strategic planning for a comprehensive
      quality-improvement program that was implemented over 5 years. The program
      included identifying and measuring key performance indicators, establishing
      specific "pillar" goals, aligning behaviors with goals and values, and training
      leaders. RESULTS: Assessment of key performance indicators over 5 years
      demonstrated progress toward achieving college goals for student and faculty
      satisfaction, research funding, numbers of students seeking formal postgraduate
      training, and private giving. CONCLUSIONS: Implementation of a continuous quality
      improvement program based on the Studer program enabled the college to focus on
      and meet its yearly and strategic goals for all components of its mission.

PMID- 23966721
TI  - Correlation of the Health Sciences Reasoning Test with student admission
      variables.
AB  - OBJECTIVES: To assess the association between scores on the Health Sciences
      Reasoning Test (HSRT) and pharmacy student admission variables. METHODS: During
      the student admissions process, cognitive data, including undergraduate grade
      point average and Pharmacy College Admission Test (PCAT) scores, were collected
      from matriculating doctor of pharmacy (PharmD) students. Between 2007 and 2009,
      the HSRT was administered to 329 first-year PharmD students. Correlations between
      HSRT scores and cognitive data, previous degree, and gender were examined.
      RESULTS: After controlling for other predictors, 3 variables were significantly
      associated with HSRT scores: percentile rank on the reading comprehension
      (p<0.001), verbal (p<0.001), and quantitative (p<0.001) subsections of the PCAT.
      CONCLUSIONS: Scores on the reading comprehension, verbal, and quantitative
      sections of the PCAT were significantly associated with HSRT scores. Some
      elements of critical thinking may be measured by these PCAT subsections. However,
      the HSRT offers information absent in standard cognitive admission criteria.

PMID- 23966722
TI  - The 4-year evolution of a social and behavioral pharmacy course.
AB  - OBJECTIVE: To evaluate the impact of 3 sequential course revisions on student
      performance in and perceived value of a social science-based course. DESIGN: The
      initial revision emphasized study of the primary literature and traditional
      assessments of student learning. Subsequent course revisions emphasized active
      learning and reflective assessment methodologies. ASSESSMENT: The syllabi, grade
      distributions, and course evaluations were collected at baseline and after each
      revision and compared. Student performance in and their perceived value of the
      course declined after the initial course revision, but significantly improved
      after subsequent revisions with performance measures returning to baseline.
      CONCLUSION: Positioning social science-based courses as a bridge to practice
      while using active-learning techniques to deliver content had a positive impact
      on students' perceived value of this Social and Behavioral Pharmacy course
      without compromising performance measures.

PMID- 23966723
TI  - A depression training session with consumer educators to reduce stigmatizing
      views and improve pharmacists' depression care attitudes and practices.
AB  - OBJECTIVE: To measure the impact of a depression training day for pharmacists
      that included a 75-minute session with a consumer educator. DESIGN: The training
      day included interactive lectures on depression; the effects and side effects of
      and indications for the use of antidepressants; adherence issues; non-drug
      treatment options for depression; and basic skills in communication. Pharmacists
      also participated in a session with a consumer educator and in counseling
      exercises that included role playing. ASSESSMENT: The study used a randomized,
      clustered, comparative design to measure pharmacists' stigma, attitudes, and
      current practice related to the provision of pharmaceutical care to people with
      depression. Mean scores for depression-care practice after the training session
      were significantly higher in the intervention group than in the control group.
      Analysis of the changes between baseline and postintervention measures in both
      the control and intervention groups confirmed a significant difference in the
      change in both social distance and practice but no significant difference in the
      change in attitude between the 2 groups of pharmacists. CONCLUSION: A continuing
      education depression training day for pharmacists that involve consumer educators
      may improve the care delivered in the community pharmacy to people with
      depression.

PMID- 23966724
TI  - An integrated course in pain management and palliative care bridging the basic
      sciences and pharmacy practice.
AB  - OBJECTIVE: To describe the development of an integrated pain and palliative care
      course and to investigate the long-term effectiveness of the course during doctor
      of pharmacy (PharmD) students' advanced pharmacy practice experiences (APPEs) and
      in their practice after graduation. DESIGN: Roseman University College of
      Pharmacy faculty developed a 3-week elective course in pain and palliative care
      by integrating relevant clinical and pharmaceutical sciences. Instructional
      strategies included lectures, team and individual activities, case studies, and
      student presentations. ASSESSMENT: Students who participated in the course in
      2010 and 2011 were surveyed anonymously to gain their perception about the class
      as well as the utility of the course during their APPEs and in their everyday
      practice. Traditional and nontraditional assessment of students confirmed that
      the learning outcomes objectives were achieved. CONCLUSIONS: Students taking the
      integrated course on pain management and palliative care achieved mastery of the
      learning outcome objectives. Surveys of students and practicing pharmacists who
      completed the course showed that the learning experience as well as retention was
      improved with the integrated mode of teaching. Integrating basic and clinical
      sciences in therapeutic courses is an effective learning strategy.

PMID- 23966725
TI  - Incremental development of an integrated assessment method for the professional
      curriculum.
AB  - OBJECTIVE: To incrementally create and embed biannual integrated knowledge and
      skills examinations into final examinations of the pharmacy practice courses
      offered in the first 3 years of the pharmacy curriculum that would account for
      10% of each course's final course grade. DESIGN: An ad hoc integrated examination
      committee was formed and tasked with addressing 4 key questions. Integrated
      examination committees for the first, second, and third years of the curriculum
      were established and tasked with identifying the most pertinent skills and
      knowledge-based content from each required course in the curriculum, developing
      measurable objectives addressing the pertinent content, and creating or revising
      multiple-choice and performance-based questions derived from integrated
      examination objectives. An Integrated Examination Review Committee evaluated all
      test questions, objectives, and student performance on each question, and revised
      the objectives and questions as needed for the following year's iteration. Eight
      performance objectives for the examinations were measured. ASSESSMENT: All 8
      performance objectives were achieved. Sixty-four percent of the college's faculty
      members participated in the integrated examination process, improving the quality
      of the examination. The incremental development and implementation of the
      examinations over a 3-year period minimized the burden on faculty time while
      engaging them in the process. Student understanding of expectations for knowledge
      and skill retention in the curriculum also improved. CONCLUSIONS: Development of
      biannual integrated examinations in the first 3 years of the classroom curriculum
      enhanced the college's culture of assessment and addressed accreditation
      guidelines for formative and summative assessment of students' knowledge and
      skills. The course will continue to be refined each year.

PMID- 23966726
TI  - Student preferences regarding teaching methods in a drug-induced diseases and
      clinical toxicology course.
AB  - OBJECTIVES: To determine which teaching method in a drug-induced diseases and
      clinical toxicology course was preferred by students and whether their preference
      correlated with their learning of drug-induced diseases. DESIGN: Three teaching
      methods incorporating active-learning exercises were implemented. A survey
      instrument was developed to analyze students' perceptions of the active-learning
      methods used and how they compared to the traditional teaching method (lecture).
      Examination performance was then correlated to students' perceptions of various
      teaching methods. ASSESSMENT: The majority of the 107 students who responded to
      the survey found traditional lecture significantly more helpful than active
      learning methods (p=0.01 for all comparisons). None of the 3 active-learning
      methods were preferred over the others. No significant correlations were found
      between students' survey responses and examination performance. CONCLUSIONS:
      Students preferred traditional lecture to other instructional methods. Learning
      was not influenced by the teaching method or by preference for a teaching method.

PMID- 23966727
TI  - Impact of a required pharmaceutical calculations course on mathematics ability
      and knowledge retention.
AB  - OBJECTIVE: To assess doctor of pharmacy (PharmD) students' mathematics ability by
      content area before and after completing a required pharmaceutical calculations
      course and to analyze changes in scores. METHODS: A mathematics skills assessment
      was administered to 2 cohorts of pharmacy students (class of 2013 and 2014)
      before and after completing a pharmaceutical calculations course. The posttest
      was administered to the second cohort 6 months after completing the course to
      assess knowledge retention. RESULTS: Both cohorts performed significantly better
      on the posttest (cohort 1, 13% higher scores; cohort 2, 15.9% higher scores).
      Significant improvement on posttest scores was observed in 6 of the 10 content
      areas for cohorts 1 and 2. Both cohorts scored lower in percentage calculations
      on the posttest than on the pretest. CONCLUSIONS: A required, 1-credit-hour
      pharmaceutical calculations course improved PharmD students' overall ability to
      perform fundamental and application-based calculations.

PMID- 23966728
TI  - Student engagement in pharmacology courses using online learning tools.
AB  - OBJECTIVE: To assess factors influencing student engagement with e-tools used as
      a learning supplement to the standard curriculum in pharmacology courses. DESIGN:
      A suite of 148 e-tools (interactive online teaching materials encompassing the
      basic mechanisms of action for different drug classes) were designed and
      implemented across 2 semesters for third-year pharmacy students. ASSESSMENT:
      Student engagement and use of this new teaching strategy were assessed using a
      survey instrument and usage statistics for the material. Use of e-tools during
      semester 1 was low, a finding attributable to a majority (75%) of students either
      being unaware of or forgetting about the embedded e-tools and a few (20%) lacking
      interest in accessing additional learning materials. In contrast to semester 1, e
      tool use significantly increased in semester 2 with the use of frequent reminders
      and announcements (p<0.001). CONCLUSION: The provision of online teaching and
      learning resources were only effective in increasing student engagement after the
      implementation of a "marketing strategy" that included e-mail reminders and
      motivation.

PMID- 23966729
TI  - A pharmacokinetics module taught within a pediatrics pharmacotherapy course.
AB  - OBJECTIVE: To review the effectiveness of a pedagogical approach and methods used
      to teach pediatric pharmacokinetics to a large class of pharmacy students in a
      required course in the third-year of a bachelor of science in pharmacy program.
      DESIGN: The pharmacokinetic sessions emphasized facilitating student
      understanding of the basic pharmacokinetic principles learned in earlier courses
      and applying that knowledge to pediatric case scenarios. This was accomplished
      using lectures with PowerPoint slides followed by small-group, context-focused
      discussions that required students to apply the principles outlined in the
      lecture. EVALUATION: Student understanding of the pharmacokinetics concepts
      discussed within the course was assessed via a written examination. CONCLUSION:
      The small-group context-focused approach to teaching pediatric pharmacokinetics
      in a large class size with minimal resources allowed opportunities for students
      to apply their foundational knowledge in an interactive and engaging atmosphere.

PMID- 23966730
TI  - Integration of problem-based learning and innovative technology into a self-care
      course.
AB  - OBJECTIVE: To assess the integration of problem-based learning and technology
      into a self-care course. DESIGN: Problem-based learning (PBL) activities were
      developed and implemented in place of lectures in a self-care course. Students
      used technology, such as computer-generated virtual patients and iPads, during
      the PBL sessions. ASSESSMENTS: Students' scores on post-case quizzes were higher
      than on pre-case quizzes used to assess baseline knowledge. Student satisfaction
      with problem-based learning and the use of technology in the course remained
      consistent throughout the semester. CONCLUSION: Integrating problem-based
      learning and technology into a self-care course enabled students to become active
      learners.

PMID- 23966732
TI  - An interprofessional psychiatric advanced pharmacy practice experience.
AB  - OBJECTIVE: To create an interprofessional psychiatry advanced pharmacy practice
      experience (APPE) and assess the initial outcomes. DESIGN: An elective psychiatry
      APPE was developed in a setting of interdisciplinary practice. Preceptor
      responsibilities were shared between a psychiatric pharmacist and an attending
      psychiatrist or psychiatric nurse practitioner. Students were also given the
      opportunity to shadow and work with other health care professionals such as
      nurses, social workers, therapists, family nurse practitioners, and utilization
      review staff members. ASSESSMENT: Midpoint and final evaluations demonstrated
      student advancement throughout the experience as well as the development of
      communication skills with patients and an increased ability to work
      collaboratively with other health care providers. Students rated this practice
      experience highly and their comments reflected achievement of the established
      learning objectives. CONCLUSION: An interdisciplinary elective practice
      experience in psychiatry at a local teaching hospital was effective in teaching
      psychiatric care and interprofessional interaction. This teaching model can be
      adapted for use in other practice settings or specialty areas.

PMID- 23966731
TI  - Enhancing team-based active learning through hands-on experience with nicotine
      replacement therapy.
AB  - OBJECTIVES: To enhance tobacco cessation active-learning in an ambulatory care
      elective course by adding hands-on experience with nicotine replacement therapy
      to a team-based learning (TBL) session. DESIGN: A hands-on experience that
      included students chewing a piece of nicotine gum was added to a TBL class
      session. Student pairs used a skills checklist to evaluate and give peer feedback
      on appropriate counseling and gum use. ASSESSMENT: Students' scores on a tobacco
      cessation examination were higher than those of students enrolled in the previous
      course in which TBL alone had been used. Based on pre- and post-experience survey
      responses, students' perceptions regarding their abilities to provide tobacco
      cessation counseling improved. Subjective student comments regarding the
      experience were positive. CONCLUSION: Participating in a TBL session that
      incorporated hands-on experience with nicotine gum in an ambulatory care elective
      course increased students' confidence in their ability to provide tobacco
      cessation counseling and provided a unique perspective on the product's
      characteristics.

PMID- 23966733
TI  - Repeated testing to improve skills in a pharmacy practice laboratory course.
AB  - OBJECTIVE: To evaluate the impact of repeated simulations and testing on the
      pharmacy practice skills development of third-year doctor of pharmacy (PharmD)
      students. DESIGN: A pharmacy practice skills laboratory was redesigned to
      reinforce skills development and enhance retention. Timed, repeated learning
      experiences that increased in complexity throughout the semester were used to
      test student knowledge, skills, and abilities. ASSESSMENT: Over a 5-year period,
      scores from skills-based activities deemed essential to professional practice and
      repeated 4 or more times in the course were analyzed. There was a significant
      improvement in scores on drug utilization reviews and patient counseling
      simulations despite the increasing difficulty and complexity of the medication
      problems presented (p <0.001). Students' scores on prescription verification and
      sterile product verification also improved significantly over 3 assessments (p
      <0.001), but then plateaued, with less improvement seen in performance on
      subsequent assessments. CONCLUSION: Providing multiple opportunities for students
      to conduct or simulate pharmacy practice activities and then test their knowledge
      and skills improves students' learning and performance.

PMID- 23966734
TI  - An elective course on pharmacy-based health screenings.
AB  - OBJECTIVE: To provide an elective course for pharmacy students focused on the
      knowledge and skills necessary to implement health screenings in a pharmacy
      environment. DESIGN: Course lectures focused on expert recommendations for health
      screenings as well as regulatory requirements and procedures integral to the
      implementation of screening services. Workshops provided hands-on experience with
      blood glucose, body composition, bone density, and cholesterol testing devices.
      ASSESSMENT: Attainment of knowledge and skills was assessed by patient case
      assignments, screening device demonstrations, group projects, and a final quiz.
      Annual course evaluations revealed consistently favorable student feedback
      regarding the course design and content. students reported a high level of
      preparedness and interest in participating in health screening services in future
      practice. CONCLUSION: An elective course focused on the delivery of health
      screenings in pharmacy settings was well received by student participants and
      exposed students to a unique opportunity in patient care.

PMID- 23966735
TI  - Should the PharmD degree be the basic educational requirement in India for
      pharmacists?

PMID- 23966736
TI  - The need for a national level competency or licensing examination for the Doctor
      of Pharmacy degree in India.

PMID- 23966737
TI  - Practice of pharmacy and language competency: delivery of integrated cross
      cultural care.

PMID- 23966738
TI  - The pharmacy student population: applications received 2011-12, degrees conferred
      2011-12, fall 2012 enrollments.

PMID- 23966739
TI  - Problems associated with treating visual impairment in resource-poor settings.

PMID- 23966740
TI  - Progress with the implementation of kangaroo mother care in four regions in
      Ghana.
AB  - AIM: To measure progress with the implementation of kangaroo mother care (KMC)
      for low birth-weight (LBW) infants at a health systems level. DESIGN: Action
      research design, with district and regional hospitals as the unit of analysis.
      SETTING: Four regions in Ghana, identified by the Ghana Health Service and
      UNICEF. PARTICIPANTS: Health workers and officials, health care facilities and
      districts in the four regions. INTERVENTION: A one-year implementation programme
      with three phases: (1) introduction to KMC, skills development in KMC practice
      and the management of implementation; (2) advanced skills development for
      regional steering committee members; and (3) an assessment of progress at the end
      of the intervention. MAIN OUTCOME MEASURES: Description of practices, services
      and facilities for KMC and the identification of strengths and challenges.
      RESULTS: Twenty-six of 38 hospitals (68%) demonstrated sufficient progress with
      KMC implementation. Half of the hospitals had designated a special ward for KMC.
      66% of hospitals used a special record for infants receiving KMC. Two of the main
      challenges were lack of support for mothers who had to remain with their LBW
      infants in hospital and no follow-up review services for LBW infants in 39% of
      hospitals. CONCLUSIONS: It was possible to roll out KMC in Ghana, but further
      support for the regions is needed to maintain the momentum. Lessons learned from
      this project could inform further scale-up of KMC and other projects in Ghana.

PMID- 23966741
TI  - Couching techniques for cataract treatment in Osogbo, South west Nigeria.
AB  - BACKGROUND: Couching is still being practised in developing countries including
      Nigeria despite its adverse effects on vision. OBJECTIVES: To find out the
      different techniques of couching, highlight the unacceptable poor visual sequelae
      and assess knowledge, attitudes, and practices of subjects. SETTINGS AND DESIGN:
      Clinic based and prospective observational study. METHODS AND MATERIAL:
      Structured interview and clinical examination of consecutive patients was used to
      obtain information. RESULTS: Fifteen subjects and 20 eyes of 9(60%) males and
      6(40%) females were studied. Age range 60 -90 years and mean 72.4+/-8.0.
      Commonest presenting complaints were "I cannot see properly/clearly" 4(26.7%) and
      "I want to do my second eye so I can see better" 3(20%). Presenting Versus (vs.)
      Corrected visual acuity (VA) was75% vs 60% blind, 55% vs 45% low vision, and 0%
      vs 10% normal vision, p= 0.032. Friends and neighbours mostly introduced subjects
      to couching (26.7% each). Commonest methods involved using sharp objects/needling
      45% and blunt/grooving/rocking methods (30%). Subjects assumed "supine" position
      75% of time. Eighty five percent of eyes were done at the coucher's. Procedure
      was painful in 73.3%. Only 5 eyes (25%) maintained vision for >10years. Thirteen
      (86.7%) said "no" to a repeat procedure and 93.4% would advice against couching.
      CONCLUSIONS: Couching methods used were very crude and archaic with attendant
      poor quality of vision and dissatisfaction. Public education, affordable and
      accessible cataract surgical services taken to the rural communities could
      gradually phase out couching.

PMID- 23966742
TI  - Attitude and beliefs of Nigerian undergraduates to spectacle wear.
AB  - BACKGROUND: Uncorrected refractive error is a common cause of preventable visual
      impairment. Glasses are the cheapest and commonest form of correction of
      refractive errors. To achieve this, patients must exhibit good compliance to
      spectacle wear. Patients' attitude and perception of glasses and eye health could
      affect compliance to spectacle wear. OBJECTIVE: To determine the attitude and
      beliefs of Nigerian undergraduates to spectacle wear. METHOD: A cross sectional
      study of 500 undergraduates of the University of Benin, Nigeria. Age range was
      from 18 to 30 years, mean age 23 +/- 2.7 years. There were 269 males and 231
      females. Semi structured questionnaires were distributed to the participants and
      collected same day after completion. RESULTS: Two-thirds (68%) of the total
      population studied had not heard of refractive error. About a third (38%)
      believed wearing eyeglasses was one of the methods used to correct refractive
      error. Half (50%) believed they would wear spectacles if prescribed with one by
      their doctor. Sixty-four percent believed eyeglasses are harmful to the eyes; and
      65% did not know that eyeglasses could be used to relieve other forms of ocular
      discomfort like headache and tearing. Fifty-seven per cent of respondents saw
      people who wore eyeglasses as visually handicapped, while 60% believed that
      eyeglasses were meant for old people. Majority of the respondents (56%) believed
      that they would be teased if they wore glasses. CONCLUSION: Knowledge of
      refractive errors and acceptance of glasses for the correction of refractive
      errors among Nigerian undergraduates is not encouraging. Public enlightenment
      programs to promote benefits of wearing prescribed spectacles are needed.

PMID- 23966743
TI  - The role of bone marrow aspirate and trephine samples in haematological diagnoses
      in patients referred to a teaching hospital in Ghana.
AB  - INTRODUCTION AND METHODS: A bone marrow examination had been requested by the
      referring clinician in over half of the 250 patients referred to the haematology
      clinic at Konfo Anokye Teaching Hospital (KATH) between 1988 and 1998 for
      investigations for various haematological disorders. Although a full blood count
      and a peripheral blood film can go a long way to resolve some of these diagnostic
      challenges faced by doctors in the districts, this information was generally not
      provided in the referral letter. After careful selection, 80 patients actually
      underwent a bone marrow examination. The result of the full blood count and
      peripheral film were available before bone marrow sampling was done. RESULTS:
      Lymphoproliferative disorders were the most common diseases that caused
      infiltration of the bone marrow. 27.5% of lymphomas were diagnosed on
      morphological examination of the bone marrow as high grade B cell NHL, 13.75% had
      tropical splenic lymphoma, 10% had chronic lymphocytic leukaemia (CLL) and 5% had
      disseminated high grade T cell lymphoma and 2.5% had Adult T cell Leukaemia
      Lymphoma (ATLL). Other disorders diagnosed after bone marrow examination include
      myelodysplastic syndrome (MDS), aplastic anaemia, megaloblastic anaemia and
      myelofibrosis. Only 8.75% of these patients had a normal bone marrow.
      CONCLUSIONS: This study has demonstrated the complexity of using bone marrow
      examination in clinical diagnosis and emphasizes the need for referring
      clinicians to consider involving specialist input in difficult haematological
      cases before requesting bone marrow examination for their patients.

PMID- 23966744
TI  - Helicobacter pylori infection in Nigerians with dyspepsia.
AB  - BACKGROUND: Helicobacter pylori is the most common chronic bacterial infection,
      and a significant aetiological factor in acid peptic diseases and gastric cancer.
      Dyspepsia is a common gastrointestinal disorder, and the most common indication
      for gastroscopy. Detection of this organism during endoscopy has become standard
      clinical practice. We determine the prevalence of H. pylori infection among
      dyspeptic patients using serology and histology. METHODS: Patients with dyspepsia
      underwent gastroscopy, and biopsies were taken from the antral portions of their
      stomach and processed. Their serum samples were tested for H. pylori infection
      using ELISA to detect anti-bodies. RESULTS: One hundred and twenty-five patients,
      comprising 49 (39.2%) males and 76 (60.8%) females were studied. A prevalence
      rate of 93.6% for H. pylori was found by serology while a rate of 80.0% was found
      by histology. CONCLUSION: There is a high prevalence of H. pylori infection in
      patients with dyspepsia; and a high percentage of detection by serological and
      histological tests.

PMID- 23966745
TI  - Low level of transmitted HIV Drug resistance at two HIV care centres in Ghana: a
      threshold survey.
AB  - BACKGROUND: As access to antiretroviral therapy (ART) increases, the emergence
      and transmission of HIV drug resistant strains becomes a major problem. The World
      Health Organization (WHO) therefore recommends an initial minimum-resource method
      to signal when transmitted HIV drug resistance (HIVDR) requires action.
      OBJECTIVE: This survey sought to generate information on the presence of HIV drug
      resistant strains in the locality where Ghana's ART for HIV was first introduced.
      METHODS: The Ghana HIVDR threshold survey (TS) was conducted and analyzed
      according to WHO strategy for surveillance of HIVDR in the Eastern Region of
      Ghana. Sixty (60) plasma specimens were collected from 2007 to 2009 by an
      unlinked anonymous method from HIV seropositive pregnant women, aged between 15
      to24 years, who were with their first pregnancy and ART naive. Genotyping was
      done as follows; Ribonucleic acid (RNA) was extracted from the samples and the
      protease (PR) and reverse transcriptase (RT) genes amplified and sequenced. The
      sequences were then analyzed for HIV drug resistance mutations using Stanford
      University HIV Drug Resistance Database. RESULTS: Only two individuals were found
      with major HIVDR mutations: one each in the PR and RT genes. Thus the level of
      HIVDR in the study population in 2009 was classified as low (< 5%). CONCLUSION:
      As at February 2009, transmitted drug resistance was not a serious problem in the
      Eastern Region of Ghana. However, it is important to continue monitoring tHIVDR
      in order to understand the dynamics of the evolution of HIV drug resistance in
      the country.

PMID- 23966746
TI  - Career destinations of University of Ghana Medical School graduates of various
      year groups.
AB  - BACKGROUND: To report on the current career destination of the University of
      Ghana Medical School (UGMS) qualified doctors in the year groups, 1998, 2000,
      2003, 2005 and 2008. DESIGN: Interview of doctors from each year group currently
      working at the Korle-Bu Teaching Hospital corroborated by phone calls to the
      doctors. SUBJECTS: All Ghanaian doctors from each graduating year group. MAIN
      OUTCOME MEASURES: 1. Current location of employment in Ghana or abroad, 2. Gender
      ratios of the doctors retained in Ghana. RESULTS: Three hundred and seventy-two
      (372) UGMS doctors consisting of 353 Ghanaians and 19 foreign students graduated
      over the five year groups. Of the 353 Ghanaians, 113 emigrated, while all but one
      of the 240 living in Ghana, practice medicine. The retention rate improved from
      54.2% in 1998 to 86.3% in 2008. The overall retention rate however is 68.0% while
      the retention rates for the male and female doctors were 69.3% and 64.6%
      respectively. Of the 177 doctors practicing in Ghana from the first 4 year-groups
      (i.e. 1998, 2000, 2003 and 2005,) 139 (i.e. 31, 31, 34 and 43 from the respective
      year groups) have either completed postgraduate training or are in the residency
      training programme. Thus 78.5% of these doctors working in Ghana have opted for
      postgraduate training. CONCLUSION: The establishment of the GCPS and to a lesser
      extent the introduction of the ADHA before it appear to have slowed down the
      medical brain drain as more and more doctors avail themselves of the local
      opportunities. The GCPS therefore needs supporting effectively in order to
      continue to be a strong incentive for the retention of doctors in Ghana, apart
      from helping to staff district general hospitals with specialists.

PMID- 23966747
TI  - Multicentric Castleman's disease in a Ghanaian adult.
AB  - Castleman's disease is a rare cause of lymphoid hyperplasia that may result in
      localized symptoms or an aggressive, multisystem disorder that can mimic other
      diseases like lymphoma or tuberculosis. We describe a case of a 55-year-old
      Ghanaian male who was successfully diagnosed and managed for multicentric
      Castleman's disease with combination chemotherapy. 

PMID- 23966748
TI  - A sudden total loss of vision after routine cataract surgery.
AB  - We share our experience of a 50-year-old controlled hypertensive woman who had
      routine cataract surgery in her left eye. She was given retrobulbar Xylocaine
      with adrenalin and postoperative gentamycin. She subsequently became blind in the
      operated eye after developing macular infarction by the first day post operative
      and optic atrophy by 2 months postoperative. This could have been caused by
      vascular occlusion in an already compromised artherosclerosed vessels. It could
      also have been due to gentamyin toxicity. Gentamycin injection given
      subconjunctivally is known to rarely result in severe retinal toxicity. This case
      illustrates that even though cataract surgery is considerd a simple routine
      procedure, and is performed in high volumes, it is not without its blinding
      complications. We recommend that the use of adrenaline in xylocaine should be
      used with caution in hypertensive patients and also the routine use of
      subconjunctival gentamycin injection after cataract surgery should be reviewed
      and other modes of endophthalmitis prophylaxis be considered. 

PMID- 23966749
TI  - Highly(>=98%) Selective Trisubstituted Alkene Synthesis of Wide Applicability via
      Fluoride-Promoted Pd-Catalyzed Cross-Coupling of Alkenylboranes.
AB  - (Z)-beta-bromo-1-propenyl(pinacol)borane(4), recently made available in 85% yield
      as a >=98% isomerically pure compound via bromoboration of 1-propyne, has been
      converted to beta-alkyl-, aryl-, and alkenyl-substituted (Z)-2-methyl-1
      alkenyl(pinacol)boranes(2a) in ca. 75% yield based on propyne via Pd-catalyzed
      Negishi alkenylation with suitable organozinc bromide. The previously sluggish
      and modest-yielding Suzuki alkenylation of beta,beta-disubstituted alkenylboranes
      has been significantly promoted by fluorides, especially nBu4NF(TBAF) or CsF to
      give trisubstituted alkenes, i.e., (Z)-beta-Me-substituted 3-i-3-xi and (E)-beta
      Ph-substituted 2b-i and 2b-ii. In all cases, each alkene product was formed in a
      >=98% seteoselectivity. The propyne-based protocol nicely complements the widely
      used Zr-catalyzed alkyne methylalumination-Pd-catalyzed alkenylation by providing
      a highly stereoselective(>=98%) route to (Z)-Me-substituted alkenes.

PMID- 23966750
TI  - Parameter Reconstruction of Vibration Systems from Partial Eigeninformation.
AB  - Quadratic matrix polynomials are fundamental to vibration analysis. Because of
      the predetermined interconnectivity among the constituent elements and the
      mandatory nonnegativity of the physical parameters, most given vibration systems
      will impose some inherent structure on the coefficients of the corresponding
      quadratic matrix polynomials. In the inverse problem of reconstructing a
      vibration system from its observed or desirable dynamical behavior, respecting
      the intrinsic structure becomes important and challenging both theoretically and
      practically. The issue of whether a structured inverse eigenvalue problem is
      solvable is problem dependent and has to be addressed structure by structure. In
      an earlier work, physical systems that can be modeled under the paradigm of a
      serially linked mass-spring system have been considered via specifically
      formulated inequality systems. In this paper, the framework is generalized to
      arbitrary generally linked systems. In particular, given any configuration of
      interconnectivity in a mass-spring system, this paper presents a mechanism that
      systematically and automatically generates a corresponding inequality system. A
      numerical approach is proposed to determine whether the inverse problem is
      solvable and, if it is so, computes the coefficient matrices while providing an
      estimate of the residual error. The most important feature of this approach is
      that it is problem independent, that is, the approach is general and robust for
      any kind of physical configuration. The ideas discussed in this paper have been
      implemented into a software package by which some numerical experiments are
      reported.

PMID- 23966751
TI  - On the Nonnegative Rank of Euclidean Distance Matrices.
AB  - The Euclidean distance matrix for n distinct points in R r is generically of rank
      r + 2. It is shown in this paper via a geometric argument that its nonnegative
      rank for the case r = 1 is generically n.

PMID- 23966752
TI  - Marriage Institutions and Sibling Competition: Evidence from South Asia*
AB  - Using data from South Asia, this article examines how arranged marriage
      cultivates rivalry among sisters. During marriage search, parents with multiple
      daughters reduce the reservation quality for an older daughter's groom, rushing
      her marriage to allow sufficient time to marry off her younger sisters. Relative
      to younger brothers, younger sisters increase a girl's marriage risk; relative to
      younger singleton sisters, younger twin sisters have the same effect. These
      effects intensify in marriage markets with lower sex ratios or greater parental
      involvement in marriage arrangements. In contrast, older sisters delay a girl's
      marriage. Because girls leave school when they marry and face limited earning
      opportunities when they reach adulthood, the number of sisters has well-being
      consequences over the life cycle. Younger sisters cause earlier school-leaving,
      lower literacy, a match to a husband with less education and a less skilled
      occupation, and (marginally) lower adult economic status. Data from a broader set
      of countries indicate that these cross-sister pressures on marriage age are
      common throughout the developing world, although the schooling costs vary by
      setting. JEL Codes: J1, I25, O15.

PMID- 23966753
TI  - Associations between personality traits, physical activity level, and muscle
      strength.
AB  - Associations among personality as measured by the Five Factor Model, physical
      activity, and muscle strength were assessed using data from the Baltimore
      Longitudinal Study of Aging (N = 1220, age: mean = 58, SD = 16). General linear
      modeling with adjustment for age, sex, race, and body mass index, and
      bootstrapping for mediation were used. We found neuroticism and most of its
      facets to negatively correlate with strength. The extraversion domain and its
      facets of warmth, activity, and positive-emotions were positively correlated with
      strength, independent of covariates. Mediation analysis results suggest that
      these associations are partly explained by physical activity level. Findings
      extend the evidence of an association between personality and physical function
      to its strength component and indicate health behavior as an important pathway.

PMID- 23966754
TI  - Pharmacologic treatment strategies in children with type 2 diabetes mellitus.
AB  - We treated 80 obese and 28 nonobese children diagnosed as having type 2 diabetes
      mellitus (T2DM). Among these patients, 26 obese and 23 nonobese children were
      assigned to pharmacologic therapies during the course of diabetes. Pharmacologic
      therapies were started if the HbA1c (NGSP) value exceeded 7.0% despite dietary
      and exercise management. For the 26 obese patients, metformin alone or in
      combination with an additional medication was frequently used. Only 2 patients
      independently received sulfonylureas (SUs) in the form of glimepiride. In
      addition, 9 patients were treated with basal insulin supported with oral
      hypoglycemic drugs (OHDs) or biphasic premix insulin. On the other hand, the 23
      nonobese patients were frequently treated with insulin alone or in combination
      with an additional medication followed by SUs. The nonobese patients tended to
      require pharmacologic therapies, in particular insulin, at an earlier stage of
      diabetes as compared with the obese patients. New antidiabetic drugs, DPP-4
      inhibitors and GLP-1 receptor agonists, seemed to exert positive effects on
      glycemic control without occurrence of hypoglycemic episodes in some patients
      regardless of the type of diabetes. These results suggest that pharmacologic
      treatment strategies in childhood T2DM should be tailored to individual patient
      characteristics. 

PMID- 23966755
TI  - Treatment of Hypophosphatemic Rickets with Phosphate and Active Vitamin D in
      Japan: A Questionnaire-based Survey.
AB  - Hereditary hypophosphatemic rickets represented by X-linked hypophosphatemic
      rickets (XLH) is a rare disorder characterized by hypophosphatemia, elevated
      alkaline phosphatase (ALP) and undermineralization of bone. Active vitamin D and
      phosphate are administered to correct hypophosphatemia and elevation of ALP.
      Overtreatment with phosphate leads to secondary hyperparathyroidism, and a large
      dose of active vitamin D has a risk of hypercalciuria. To understand the
      situation concerning treatment of patients with hereditary hypophosphatemic
      rickets in Japan, we conducted a questionnaire survey of pediatric
      endocrinologists. Answers were obtained from 53 out of 68 hospitals where the
      pediatric endocrinologists worked. One hundred and thirty-five patients were
      treated in 28 hospitals during November 2009 and May 2010; 126 patients suffered
      from hereditary hypophosphatemic rickets, and 9 had hypophosphatemia caused by
      other miscellaneous reasons. The distribution of patient age was as follows: 27
      (21%) were between 6 mo and 6 yr of age, 39 (31%) were between 6 and 12 yr of
      age, and 60 (48%) were more than 12 yr of age. Active vitamin D was given to 123
      patients, and phosphate was given to 106 patients. As for the dose of phosphorus,
      37.2-58.1 mg/kg/d was given divided into 2 to 6 aliquots. There were various
      control targets of treatment, including serum phosphate, serum ALP, rachitic
      change, urinary Ca/Cr, parathyroid hormone and growth. It is very important to
      avoid side effects of these treatments. No evidence is available about the
      optimal dose of phosphate or number of administrations in the treatment of
      patients with hypophosphatemic rickets. Although there is a recommendation for
      clinical management of patients with hypophosphatemic rickets, we should set a
      clinical guideline for it in Japan. 

PMID- 23966756
TI  - A case of graves' disease diagnosed in the course of bilateral carotid artery
      stenoses (moyamoya disease); a case report and review of the literature.
AB  - A 14-year-old boy was admitted to our hospital after being diagnosed at a local
      clinic with bilateral carotid artery stenoses (Moyamoya disease) and mild
      thyrotoxicosis. A blood examination showed suppressed TSH and elevated
      triiodothyronine and thyroxine levels; however, he was negative for anti
      thyrotropin receptor antibody (TRAB) and thyroid stimulating antibody (TSAB).
      Concern about a possible thyroid crisis led us to administer thiamazole (MMI) and
      potassium iodide (KI), following which encephalo-duro-arterio-synangiosis (EDAS)
      of the left side was performed successfully. After about 1 mo, he became positive
      for TRAB and TSAB. He was thought to have Graves' disease and Moyamoya disease
      coincidentally. Several factors are considered to be involved in the coincidental
      onset of these two diseases. 

PMID- 23966757
TI  - Association between graves' disease and renal coloboma syndrome: a case report.
AB  - Renal coloboma syndrome is an autosomal dominant condition characterized by renal
      lesions and optic nerve abnormalities. We report an 11-yr-old Japanese girl with
      familial renal coloboma syndrome, who also had Graves' disease. Four affected
      family members had a previously reported heterozygous mutation (c.76dupG,
      p.Val26Glyfs*28) in the PAX2 gene. We hypothesized that PAX2 mutations may
      increase the risk of autoimmune diseases through alterations of human beta
      defensin 1 expression. 

PMID- 23966758
TI  - Decision Analysis and Cost-effectiveness Analysis.
AB  - Healthcare decision-making can be complex, often requiring decision makers to
      weigh serious trade-offs, consider patients' values, and incorporate evidence in
      the face of uncertainty. Medical decisions are made implicitly by clinicians and
      other decision-makers on a daily basis. Decisions based largely on personal
      experience are subject to many biases. Decision analysis and cost-effectiveness
      analysis are systematic approaches used to support decision-making under
      conditions of uncertainty that involve important trade-offs. These mathematical
      tools can provide patients, physicians and policy makers with a useful approach
      to complex medical decision making.

PMID- 23966759
TI  - Developmental Characteristics of African American and Caribbean Black
      Adolescents' Attributions Regarding Discrimination.
AB  - The present study examined discrimination attributions in the psychological well
      being of Black adolescents. Findings are based on a representative sample of 810
      African American and 360 Caribbean Black youth, aged 13 to 17, who participated
      in the National Survey of American Life (NSAL). Youth completed measures of
      perceived discrimination, discrimination attributions, depressive symptoms, self
      esteem and life satisfaction. Approximately half the youth attributed
      discrimination to race/ethnicity (43%), followed by age (17%), physical
      appearance (16.5%) and gender (7.5%) and there were no ethnic, gender or age
      differences regarding discrimination attributions. Key findings suggest that the
      association between perceived discrimination and psychological did not vary
      according to discrimination attribution, which implies that discrimination is
      harmful for Black youth regardless of the attribution.

PMID- 23966760
TI  - Vulnerable Groups Living with Spinal Cord Injury.
AB  - There is considerable variation in rehabilitation outcomes within the population
      of spinal cord-injured individuals across racial and socioeconomic groups. This
      suggests that the long-term health following spinal cord injury (SCI) is
      determined, at least in part, by group differences in exposure to advantages and
      disadvantages among persons living in the community. This article conceptualizes
      the nature of vulnerability and how increased vulnerability leads to disparities
      in SCI outcomes. Demographic, socioeconomic, and geographic determinants of
      adverse outcomes among vulnerable groups are discussed. Finally, a research model
      that outlines potential processes that elicit vulnerability following SCI and
      clinical implications is reviewed.

PMID- 23966761
TI  - Improved Sparse Multi-Class SVM and Its Application for Gene Selection in Cancer
      Classification.
AB  - BACKGROUND: Microarray techniques provide promising tools for cancer diagnosis
      using gene expression profiles. However, molecular diagnosis based on high
      throughput platforms presents great challenges due to the overwhelming number of
      variables versus the small sample size and the complex nature of multi-type
      tumors. Support vector machines (SVMs) have shown superior performance in cancer
      classification due to their ability to handle high dimensional low sample size
      data. The multi-class SVM algorithm of Crammer and Singer provides a natural
      framework for multi-class learning. Despite its effective performance, the
      procedure utilizes all variables without selection. In this paper, we propose to
      improve the procedure by imposing shrinkage penalties in learning to enforce
      solution sparsity. RESULTS: The original multi-class SVM of Crammer and Singer is
      effective for multi-class classification but does not conduct variable selection.
      We improved the method by introducing soft-thresholding type penalties to
      incorporate variable selection into multi-class classification for high
      dimensional data. The new methods were applied to simulated data and two cancer
      gene expression data sets. The results demonstrate that the new methods can
      select a small number of genes for building accurate multi-class classification
      rules. Furthermore, the important genes selected by the methods overlap
      significantly, suggesting general agreement among different variable selection
      schemes. CONCLUSIONS: High accuracy and sparsity make the new methods attractive
      for cancer diagnostics with gene expression data and defining targets of
      therapeutic intervention. AVAILABILITY: The source MATLAB code are available from
      http://math.arizona.edu/~hzhang/software.html.

PMID- 23966762
TI  - Obvious optic disc swelling in a patient with cryopyrin-associated periodic
      syndrome.
AB  - Cryopyrin-associated periodic syndrome (CAPS) is a group of rare hereditary
      autoinflammatory diseases caused by mutations of the NLRP3 gene, and leads to
      excessive production of the proinflammatory cytokine, interleukin-lbeta. A 35
      year-old male presented with recurrent symptoms of urticarial-like rash, periodic
      fever, arthralgia, headache, and eye redness. His best-corrected visual acuity
      was 1.0 OD and 0.9 OS. Slit-lamp examination showed conjunctival and episcleral
      injection in both eyes. Ophthalmoscopy revealed obvious bilateral optic disc
      swelling and retinal vascular sheathing around the optic discs. Spectral domain
      optical coherence tomography also showed obvious optic disc swelling. Steroid and
      nonsteroidal anti-inflammatory drugs did not improve these symptoms. Genetic
      testing detected a heterozygous mutation of c.907G>A. Thus, the patient was
      genetically confirmed with CAPS. Visual acuity did not decrease for 3 years,
      although the optic discs became white in color. CAPS should therefore be
      distinguished from other disorders when examining optic disc swelling and/or
      uveitis patients with urticarial-like rash and periodic fever. 

PMID- 23966763
TI  - Color vision abnormality as an initial presentation of the complete type of
      congenital stationary night blindness.
AB  - Patients with the complete form of congenital stationary night blindness (CSNB)
      often have reduced visual acuity, myopia, impaired night vision, and sometimes
      nystagmus and strabismus, however, they seldom complain of color vision
      abnormality. A 17-year-old male who was at technical school showed abnormalities
      in the color perception test for employment, and was referred to our hospital for
      a detailed examination. He had no family history of color vision deficiency and
      no other symptoms. During the initial examination, his best-corrected visual
      acuity was 1.2 in both eyes. His fundus showed no abnormalities except for
      somewhat yellowish reflex in the fovea of both eyes. Electroretinogram (ERG)
      showed a good response in cone ERG and 30 Hz flicker ERG, however, the bright
      flash, mixed rod and cone ERG showed a negative type with a reduced b-wave
      (positive deflection). There was no response in the rod ERG, either. From the
      findings of the typical ERG, the patient was diagnosed with complete congenital
      stationary night blindness. This case underscores the importance of ERG in order
      to diagnose the cause of a color vision anomaly. 

PMID- 23966764
TI  - Intravitreal aflibercept for polypoidal choroidal vasculopathy after developing
      ranibizumab tachyphylaxis.
AB  - PURPOSE: To evaluate the effect of aflibercept treatment after developing
      ranibizumab tachyphylaxis for the treatment of polypoidal choroidal vasculopathy
      (PCV). PATIENTS AND METHODS: Ten eyes from ten patients with PCV who developed
      ranibizumab tachyphylaxis were reviewed. Tachyphylaxis was defined as when
      repeated intravitreal ranibizumab (IVR) resulted in a complete lack of response
      after initial treatment response. All treatments were converted to intravitreal
      aflibercept (IVA) after development of ranibizumab tachyphylaxis. Central retinal
      thickness (CRT) was compared at baseline, at complete resolution after IVR, at
      reactivation after IVR, at initial IVA, and at 4 and 12 weeks after initial IVA.
      RESULTS: Mean number of IVR treatments before conversion to IVA was 11.3 (range 5
      16). All eyes had positive therapeutic responses after conversion to IVA. Mean
      CRT at 4 and 12 weeks after initial IVA was significantly decreased from baseline
      initial IVA (P = 0.005). CONCLUSION: Switching therapy to aflibercept is
      effective for patients with PCV who develop tachyphylaxis to ranibizumab.

PMID- 23966765
TI  - Surgical results of combined pars plana vitrectomy and phacoemulsification for
      vitreous hemorrhage in PDR.
AB  - BACKGROUND: The purpose of this study was to evaluate the effectiveness, safety,
      and incidence of complications after combined clear corneal phacoemulsification
      with intraocular lens implantation and pars plana vitrectomy in eyes with
      proliferative diabetic retinopathy coexistent with significant cataract. METHODS:
      Eighty-five eyes of 85 patients with proliferative diabetic retinopathy underwent
      primary standard three-port vitrectomy with 20-gauge instruments and
      phacoemulsification with intraocular lens implantation for vitreous hemorrhage
      from 2008 to 2011. The main outcome measures were visual outcomes and surgical
      complications. RESULTS: Forty patients were male and 45 were female. Their age
      ranged from 40 to 77 years with a mean of 59.6 years. The mean follow-up was 13
      months, with a range of 6-48 months. The preoperative logMAR visual acuity
      changed from 2.62 +/- 0.6 to 0.8 +/- 0.7 postoperatively. Postoperatively, visual
      acuity improved in 79 eyes (92.9%), and did not change in six eyes (7.1%).
      Intraoperative complications were transient corneal edema (five eyes) and
      posterior capsular rupture (one eye). Postoperative complications consisted of
      transient intraocular pressure elevation (25 eyes), corneal epithelial defects
      (six eyes), anterior chamber reaction (four eyes), hyphema (two eyes), posterior
      synechiae (four eyes), vitreous hemorrhage (23 eyes), retinal tears (five eyes),
      retinal detachment (one eye), and neovascular glaucoma (one eye). CONCLUSION: Our
      study suggests that the combined operation of pars plana vitrectomy,
      phacoemulsification, and intraocular lens implantation is safe and effective for
      patients with proliferative diabetic retinopathy. We believe that the visual
      outcome and complications depended primarily on underlying posterior segment
      pathology and were not related to the combined procedure technique.

PMID- 23966766
TI  - Letter to the editor.

PMID- 23966767
TI  - Primary posterior capsular opacification in Indian rural population undergoing
      cataract surgery for hypermature senile cataract.
AB  - AIM: To find out the incidence of primary posterior capsular opacification (PCO)
      in rural patients with a hypermature senile cataract undergoing cataract surgery.
      SETTINGS: Tertiary eye care center in central India. DESIGN: Prospective,
      observational, noncomparative study. MATERIALS AND METHODS: Two-hundred eyes of
      200 patients presenting with a hypermature cataract underwent manual small
      incision cataract surgery. A single surgeon performed all surgeries under
      peribulbar anesthesia. After cortical clean-up, the capsular bag was inflated
      with viscoelastic. The presence or absence of opacity on the posterior lens
      capsule and location was noted. Postoperative follow-up was done for visual
      acuity and need for neodymium-doped yttrium aluminum garnet (ND:YAG) laser
      capsulotomy. RESULTS: Primary PCO occurred in 76 eyes (incidence of 38%). It was
      peripheral in 58 eyes (76.3%) and central in 18 eyes (23.7%). At 6 weeks
      postoperatively, best corrected visual acuity for eyes with central primary PCO
      (n = 18) was 0.2-0.3 logMAR and 0-0.2 logMAR for eyes with peripheral primary PCO
      (n = 58). Best corrected visual acuity at the 6- and 12-month follow-up was 0-0.2
      logMAR in both groups. Fibrotic primary PCO was seen in four patients. No
      predilection for the development of primary PCO to a particular quadrant of
      posterior capsule was observed. At 1 year postoperatively, eleven (14.5%)
      patients required ND:YAG laser capsulotomy, six (7.90%) of whom underwent ND:YAG
      laser capsulotomy at the 6-month follow-up. Seven patients with central primary
      PCO and four patients with peripheral primary PCO required ND:YAG laser
      capsulotomy. CONCLUSION: A high incidence of primary PCO was noted in rural
      patients with a hypermature senile cataract undergoing cataract surgery. No
      serious intraoperative complications were noted. Visual outcome at 1-year follow
      up was satisfactory. Need for early ND:YAG laser posterior capsulotomy should be
      explained to these patients before cataract surgery. No post ND:YAG capsulotomy
      complications were noted in any patient.

PMID- 23966768
TI  - Hyperautofluorescent ring in eyes with macular holes.
AB  - BACKGROUND: Fundus autofluorescence studies in eyes with macular holes (MHs) have
      shown a hyperautofluorescent spot corresponding to the hole and a
      hypoautofluorescent ring corresponding to the fluid cuff surrounding the hole.
      The purpose of this report is to present three cases of MH with a different
      fundus autofluorescence pattern. CASE REPORTS: Case 1 was a 62-year-old woman who
      did not know the duration of the MH in her left eye. Her decimal best-corrected
      visual acuity (BCVA) was 0.08. The left eye had a one-half disc diameter MH with
      a depigmented ring surrounding the area of the fluid cuff. Fundus
      autofluorescence showed a hyperautofluorescent ring corresponding to the
      depigmented ring. After vitrectomy, fundus autofluorescence showed the same size
      hyperautofluorescent ring despite the decreased size of the opened MH. Case 2 was
      a 69-year-old woman who had been diagnosed with MH in the right eye 13 years
      earlier. Her decimal BCVA was 0.1. The right eye had a one-half disc diameter MH
      with a depigmented ring surrounding the area of the fluid cuff. Fundus
      autofluorescence showed a hyperautofluorescent ring corresponding to the
      depigmented ring. Postoperative fundus autofluorescence showed the same size
      hyperautofluorescent ring despite the hole being closed. The decimal BCVA was 0.2
      in her right eye 6 months after vitrectomy. Case 3 was a 71-year-old woman who
      had been diagnosed with MH in the right eye 15 years earlier. Her decimal BCVA
      was 0.1. The right eye had a one-half disc diameter MH with a depigmented ring
      which corresponded with a hyperautofluorescent ring. Postoperative fundus
      autofluorescence showed the same size hyperautofluorescent ring despite the hole
      being closed. The decimal BCVA was 0.2 in her right eye 6 months after
      vitrectomy. CONCLUSION: Our findings suggest that a hyperautofluorescent ring in
      eyes with MHs may be an indicator of a poor surgical prognosis both anatomically
      and functionally.

PMID- 23966769
TI  - Correlation between ocular perfusion pressure and ocular pulse amplitude in
      glaucoma, ocular hypertension, and normal eyes.
AB  - BACKGROUND: The purpose of this study was to investigate the correlation between
      ocular perfusion pressure and ocular pulse amplitude in glaucoma, ocular
      hypertension, and normal eyes. METHODS: Ninety eyes from 90 patients were
      included. Thirty patients had been recently diagnosed with glaucoma and had no
      previous history of treatment for ocular hypotension, 30 had elevated intraocular
      pressure (IOP) without evidence of glaucoma, and 30 had normal IOP (<21 mmHg)
      with no detectable glaucomatous damage. Goldmann applanation tonometry (GAT),
      dynamic contour tonometry (DCT), blood pressure measurement, pachymetry, Humphrey
      visual field, and routine ophthalmic examination was performed in each patient.
      Ocular perfusion pressure was calculated as the difference between mean arterial
      pressure and IOP. The ocular pulse amplitude was given by DCT. The Pearson
      correlation coefficient was used to compare the glaucomatous and ocular
      hypertensive groups, and comparisons with the normal IOP group were done using
      the Spearman's rank correlation coefficient. RESULTS: Mean IOP by DCT was 22.7 +/
      4.3 mmHg in the glaucoma group, 22.3 +/- 2.8 mmHg in the ocular hypertension
      group, and 14.3 +/- 1.6 mmHg in the control group. Mean IOP by GAT was 19.0 +/-
      5.1 mmHg for glaucoma, 22.4 +/- 2.1 mmHg for ocular hypertension, and 12.9 +/-
      2.2 mmHg for controls. Mean ocular pulse amplitude was 3.4 +/- 1.2 mmHg in the
      glaucoma group, 3.5 +/- 1.2 mmHg in the ocular hypertension group, and 2.6 +/-
      0.9 mmHg in the control group. Mean ocular perfusion pressure was 46.3 +/- 7.9
      mmHg in the glaucoma group, 46.3 +/- 7.9 mmHg in the ocular hypertension group,
      and 50.2 +/- 7.0 mmHg in controls. No significant correlation between ocular
      perfusion pressure and ocular pulse amplitude was found in any of the groups (P =
      0.865 and r = -0.032, P = 0.403 and r = -0.156, P = 0.082 and rho = -0.307 for
      glaucoma, ocular hypertension, and normal eyes, respectively). CONCLUSION: There
      is no significant correlation between ocular perfusion pressure and ocular pulse
      amplitude values in glaucoma, ocular hypertension, or normal eyes. IOP values
      measured by GAT correlate with those measured by DCT.

PMID- 23966771
TI  - Open-source approaches for the repurposing of existing or failed candidate drugs:
      learning from and applying the lessons across diseases.
AB  - Repurposing has the objective of targeting existing drugs and failed, abandoned,
      or yet-to-be-pursued clinical candidates to new disease areas. The open-source
      model permits for the sharing of data, resources, compounds, clinical molecules,
      small libraries, and screening platforms to cost-effectively advance old drugs
      and/or candidates into clinical re-development. Clearly, at the core of drug
      repurposing activities is collaboration, in many cases progressing beyond the
      open sharing of resources, technology, and intellectual property, to the sharing
      of facilities and joint program development to foster drug-repurposing human
      capacity development. A variety of initiatives under way for drug repurposing,
      including those targeting rare and neglected diseases, are discussed in this
      review and provide insight into the stakeholders engaged in drug-repurposing
      discovery, the models of collaboration used, the intellectual property-management
      policies crafted, and human capacity developed. In the case of neglected tropical
      diseases, it is suggested that the development of human capital be a central
      aspect of drug-repurposing programs. Open-source models can support human-capital
      development through collaborative data generation, open compound access, open and
      collaborative screening, preclinical and possibly clinical studies. Given the
      urgency of drug development for neglected tropical diseases, the review suggests
      elements from current repurposing programs be extended to the neglected tropical
      diseases arena. 

PMID- 23966770
TI  - Developing therapeutic approaches for metachromatic leukodystrophy.
AB  - Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder
      caused by the deficiency of arylsulfatase A (ASA), resulting in impaired
      degradation of sulfatide, an essential sphingolipid of myelin. The clinical
      manifestations of MLD are characterized by progressive demyelination and
      subsequent neurological symptoms resulting in severe debilitation. The
      availability of therapeutic options for treating MLD is limited but expanding
      with a number of early stage clinical trials already in progress. In the
      development of therapeutic approaches for MLD, scientists have been facing a
      number of challenges including blood-brain barrier (BBB) penetration, safety
      issues concerning therapies targeting the central nervous system, uncertainty
      regarding the ideal timing for intervention in the disease course, and the lack
      of more in-depth understanding of the molecular pathogenesis of MLD. Here, we
      discuss the current status of the different approaches to developing therapies
      for MLD. Hematopoietic stem cell transplantation has been used to treat MLD
      patients, utilizing both umbilical cord blood and bone marrow sources.
      Intrathecal enzyme replacement therapy and gene therapies, administered locally
      into the brain or by generating genetically modified hematopoietic stem cells,
      are emerging as novel strategies. In pre-clinical studies, different cell
      delivery systems including microencapsulated cells or selectively neural cells
      have shown encouraging results. Small molecules that are more likely to cross the
      BBB can be used as enzyme enhancers of diverse ASA mutants, either as
      pharmacological chaperones, or proteostasis regulators. Specific small molecules
      may also be used to reduce the biosynthesis of sulfatides, or target different
      affected downstream pathways secondary to the primary ASA deficiency. Given the
      progressive neurodegenerative aspects of MLD, also seen in other lysosomal
      diseases, current and future therapeutic strategies will be complementary,
      whether used in combination or separately at specific stages of the disease
      course, to produce better outcomes for patients afflicted with this devastating
      inherited disorder. 

PMID- 23966772
TI  - Facilitators and barriers to hypertension self-management in urban African
      Americans: perspectives of patients and family members.
AB  - INTRODUCTION: We aimed to inform the design of behavioral interventions by
      identifying patients' and their family members' perceived facilitators and
      barriers to hypertension self-management. MATERIALS AND METHODS: We conducted
      focus groups of African American patients with hypertension and their family
      members to elicit their views about factors influencing patients' hypertension
      self-management. We recruited African American patients with hypertension (n =
      18) and their family members (n = 12) from an urban, community-based clinical
      practice in Baltimore, Maryland. We conducted four separate 90-minute focus
      groups among patients with controlled (one group) and uncontrolled (one group)
      hypertension, as well as their family members (two groups). Trained moderators
      used open-ended questions to assess participants' perceptions regarding patient,
      family, clinic, and community-level factors influencing patients' effective
      hypertension self-management. RESULTS: Patient participants identified several
      facilitators (including family members' support and positive relationships with
      doctors) and barriers (including competing health priorities, lack of knowledge
      about hypertension, and poor access to community resources) that influence their
      hypertension self-management. Family members also identified several facilitators
      (including their participation in patients' doctor's visits and discussions with
      patients' doctors outside of visits) and barriers (including their own limited
      health knowledge and patients' lack of motivation to sustain hypertension self
      management behaviors) that affect their efforts to support patients' hypertension
      self-management. CONCLUSION: African American patients with hypertension and
      their family members reported numerous patient, family, clinic, and community
      level facilitators and barriers to patients' hypertension self-management.
      Patients' and their family members' views may help guide efforts to tailor
      behavioral interventions designed to improve hypertension self-management
      behaviors and hypertension control in minority populations.

PMID- 23966773
TI  - Pharmacodynamics of vancomycin in elderly patients aged 75 years or older with
      methicillin-resistant Staphylococcus aureus hospital-acquired pneumonia.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections are
      associated with significant mortality and health care costs. To improve treatment
      outcomes for MRSA, a better understanding of the pharmacokinetic/pharmacodynamic
      parameters of vancomycin is required to develop optimal dosing strategies,
      particularly in elderly patients (>=75 years of age) with limited renal function.
      The purpose of this study was to determine whether pharmacokinetic indices for
      vancomycin are associated with mortality from MRSA hospital-acquired pneumonia in
      elderly patients. METHODS: We conducted a retrospective observational study with
      28-day mortality as the primary outcome for 94 patients with MRSA hospital
      acquired pneumonia who had been treated with vancomycin from January 2006 through
      December 2012. Our most recent sampling of MRSA isolates had a minimum inhibitory
      concentration (MIC) for vancomycin of 1 MUg/mL (86%), indicating that the area
      under the curve (AUC) was equal to the AUC/MIC in these isolates. The primary
      data from 28-day survivors and nonsurvivors were compared. RESULTS: Among 94
      elderly patients, the mean age was 82 (75-99) years. Multivariate analyses
      revealed that, among the factors examined, only the nonoptimal AUC (<250, >450
      MUg*h/mL) was an independent predictor of 28-day mortality in elderly patients
      (odds ratio 23.156, 95% confidence interval 6.814-78.687, P < 0.001). We detected
      a significant difference for increasing nephrotoxicity in nonsurvivors (nine of
      32 patients [28%]) compared with survivors (three of 62 patients [4.8%], P =
      0.003). CONCLUSION: This finding indicates that patients with potentially poor
      renal function are likely to have increased AUC values and a poor prognosis.
      Consideration of the pharmacokinetics/pharmacodynamics of vancomycin and
      targeting an AUC/MIC value of 250-450 MUg*h/mL may result in improved treatment
      outcomes for elderly patients with MRSA hospital-acquired pneumonia.

PMID- 23966774
TI  - Results of cataract surgery in the very elderly population.
AB  - AIM: The aim of our study was to retrospectively evaluate the effectiveness and
      safety of cataract surgery and intraocular lens implantation (IOL) for patients
      aged 90 years or older, whom we define as "very elderly." METHODS: The study
      involved a total number of 122 patients (122 eyes) with senile cataracts. The
      mean age of patients was 91.2 +/- 2.3 years (range 90-100 years old).
      Phacoemulsification (phaco) was done on 113 of 122 eyes, and 9 of 122 eyes had
      extracapsular cataract extraction (ECCE). Postoperative visual acuity and
      intraocular pressure (IOP) were analyzed on the first postoperative day, 3 months
      after surgery, and 6 months after surgery. RESULTS: Best corrected visual acuity
      (BCVA) improved in 100 of 122 eyes (82.0%). BCVA remained the same in 20 of 122
      eyes (16.4%) and decreased in 2 of 122 eyes (1.6%), mainly because of coexisting
      age-related macular degeneration (AMD). The BCVA 3 months after surgery was >=0.8
      in 23 of 122 eyes (18.9%), between 0.5 and 0.7 in 28 of 122 eyes (22.3%), and
      between 0.2 and 0.4 in 33 of 122 eyes (27.1%). We found significant implications
      of cataract surgery on decreasing IOP in the studied group of patients suffering
      from glaucoma compared to the patients without glaucoma. CONCLUSION: Advanced age
      is not a contraindication for cataract surgery. The results of the study showed
      that when systemic conditions are stable, both phaco and ECCE with IOL for very
      elderly patients are effective and safe.

PMID- 23966775
TI  - Trend of the incidence of lumbar disc herniation: decreasing with aging in the
      elderly.
AB  - BACKGROUND: Compelling evidence has shown that the incidence of lumbar disc
      herniation (LDH) increases with age. In this study, retrospective clinical
      analysis of 601 cases of LDH has been conducted to investigate the role of age in
      the incidence of LDH in the elderly. The aim of the study is to investigate the
      relationship between the process of aging and the occurrence of LDH in old
      adults. METHODS: Clinical cases (n = 601) of LDH were retrospectively analyzed.
      RESULTS: The imaging examination with computed tomography and/or magnetic
      resonance imaging showed the occurrence of degeneration in LDH patients over 65
      years of age. The most common site of LDH is toward the bottom of the spine at L4
      L5 and/or L5-S1. The incidence of LDH drops with age in the elderly, especially
      after the age of 80 years. There is an obvious decrease in LDH in the elderly
      female. CONCLUSION: A decreasing incidence of LDH with aging occurs in the
      elderly. This investigation indicates that aging is not a contributor to the
      performance of LDH in the elderly although the incidence of LDH is proportional
      to age.

PMID- 23966776
TI  - Pacemaker implantation complication rates in elderly and young patients.
AB  - AIMS: To evaluate the complication rate differences between elderly and younger
      patients who receive a permanent pacemaker implantation. METHODS: We reviewed all
      cases admitted to our institution between January 2008 and June 2009 with
      symptomatic bradyarrhythmia for whom a permanent pacemaker was implanted.
      Beginning in June 2009, we prospectively collected data from all patients with
      the same diagnosis and procedure. The frequency of complications due to the
      pacemaker implantation procedure was evaluated and compared between young (<70
      years old) and elderly (>=70 years old) patients. RESULTS: Among 574 patients
      with a permanent pacemaker, 259 patients (45.1%) were below and 315 patients
      (54.9%) were above or at 70 years of age. There were 240 (92.7%) and 19 (7.3%)
      dual-chamber pacemaker (DDD) and single-chamber pacemaker (VVI) implanted
      patients in the younger group, and 291 (76.8%) and 73 (23.2%) DDD and VVI
      pacemaker implanted patients in the elderly group, respectively. The complication
      rate was 39 (15.1%) out of 259 young patients and 24 (7.6%) out of 315 elderly
      patients. Postprocedural complications were statistically lower in the elderly
      patients than in younger patients (P = 0.005). CONCLUSION: A pacemaker
      implantation performed by an experienced operator is a safe procedure for
      patients of advanced age. The patients who are above 70 years old may have less
      complication rates than the younger patients.

PMID- 23966777
TI  - Drugs potentially affecting the extent of airways reversibility on pulmonary
      function testing are frequently consumed despite guidelines.
AB  - BACKGROUND: The increase in forced expiratory volume in one second (FEV1)
      effected by a bronchodilator is routinely assessed when patients undertake
      pulmonary function testing (PFT). Several drug classes can theoretically affect
      the magnitude of the increase in FEV1. Withholding periods are advised for many
      but not all such drugs. Anecdotally, many subjects presenting for PFT are found
      to have taken drugs that might affect the test. We did an audit of patients
      presenting for PFT to assess the frequency with which FEV1 reversibility might be
      affected by drugs. METHODS: One hundred subjects presenting to the laboratory for
      PFT were questioned about recent drug consumption by an independent pharmacy
      intern. Reversibility of FEV1 was assumed to have been affected if drugs of
      interest were consumed within defined withholding periods or two half-lives for
      drugs without such data. RESULTS: Sixty-three subjects were prescribed drugs
      likely to affect FEV1 reversibility. Thirty-six subjects consumed at least one
      such drug within the withholding period. Half (18) of these patients consumed
      beta-blockers with or without beta-agonists. Sixty-five subjects did not recall
      receiving any advice about withholding drugs prior to the test and only 10
      recalled receiving advice from their clinician or pulmonary function technician.
      CONCLUSION: Subjects presenting for PFT are infrequently advised to withhold
      drugs that may affect FEV1 reversibility, and consequently, often take such drugs
      close to the time of the test. Therefore, it is likely that the increase in FEV1
      is frequently affected by interference from drugs and this might impact on
      diagnosis and/or treatment options.

PMID- 23966778
TI  - Cisplatin-incorporated nanoparticles of poly(acrylic acid-co-methyl methacrylate)
      copolymer.
AB  - BACKGROUND: Although cisplatin is extensively used in the clinical field, its
      intrinsic toxicity limits its clinical use. We investigated nanoparticle
      formations of poly(acrylic acid-co-methyl methacrylate) (PAA-MMA) incorporating
      cisplatin and their antitumor activity in vitro and in vivo. METHODS: Cisplatin
      incorporated nanoparticles were prepared through the ion-complex formation
      between acrylic acid and cisplatin. The anticancer activity of cisplatin
      incorporated nanoparticles was assessed with CT26 colorectal carcinoma cells.
      RESULTS: Cisplatin-incorporated nanoparticles have small particle sizes of less
      than 200 nm with spherical shapes. Drug content was increased according to the
      increase of the feeding amount of cisplatin and acrylic acid content in the
      copolymer. The higher acrylic acid content in the copolymer induced increase of
      particle size and decrease of zeta potential. Cisplatin-incorporated
      nanoparticles showed a similar growth-inhibitory effect against CT26 tumor cells
      in vitro. However, cisplatin-incorporated nanoparticles showed improved antitumor
      activity against an animal tumor xenograft model. CONCLUSION: We suggest that PAA
      MMA nanoparticles incorporating cisplatin are promising carriers for an antitumor
      drug-delivery system.

PMID- 23966779
TI  - Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+
      immune cells.
AB  - The goal of this study was to develop and characterize an intravaginal
      nanomedicine for the active targeted delivery of saquinavir (SQV) to CD4(+)
      immune cells as a potential strategy to prevent or reduce HIV infection. The
      nanomedicine was formulated into a vaginal gel to provide ease in self
      administration and to enhance retention within the vaginal tract. SQV
      encapsulated nanoparticles (SQV-NPs) were prepared from poly(lactic-co-glycolic
      acid) (PLGA) and conjugated to antihuman anti-CD4 antibody. Antibody-conjugated
      SQV-NPs (Ab-SQV-NPs) had an encapsulation efficiency (EE%) of 74.4% + 3.7% and an
      antibody conjugation efficiency (ACE%) of 80.95% + 1.10%. Over 50% of total
      loaded SQV was released from NPs over 3 days. NPs were rapidly taken up by Sup-T1
      cells, with more than a twofold increase in the intracellular levels of SQV when
      delivered by Ab-SQV-NPs in comparison to controls 1 hour post-treatment. No
      cytotoxicity was observed when vaginal epithelial cells were treated for 24 hours
      with drug-free Ab-NPs (1,000 MUg/mL), 1% HEC placebo gel (200 mg/mL), or 1% HEC
      gel loaded with drug-free Ab-NPs (5 mg NPs/g gel, 200 mg/mL of gel mixture).
      Overall, we described an intravaginal nanomedicine that is nontoxic and can
      specifically deliver SQV into CD4(+) immune cells. This platform may demonstrate
      potential utility in its application as postexposure prophylaxis for the
      treatment or reduction of HIV infection, but further studies are required. 

PMID- 23966780
TI  - In situ fabrication of silver nanoparticle-filled hydrogen titanate nanotube
      layer on metallic titanium surface for bacteriostatic and biocompatible
      implantation.
AB  - A silver nanoparticle (AgNP)-filled hydrogen titanate nanotube layer was
      synthesized in situ on a metallic titanium substrate. In the synthesis approach,
      a layer of sodium titanate nanotubes is first prepared on the titanium surface by
      using a hydrothermal method. Silver nitrate solution is absorbed into the
      nanotube channels by immersing a dried nanotube layer in silver nitrate solution.
      Finally, silver ions are reduced by glucose, leading to the in situ growth of
      AgNPs in the hydrogen titanate nanotube channels. Long-term silver release and
      bactericidal experiments demonstrated that the effective silver release and
      effective antibacterial period of the titanium foil with a AgNP-filled hydrogen
      titanate nanotube layer on the surface can extend to more than 15 days. This
      steady and prolonged release characteristic is helpful to promote a long-lasting
      antibacterial capability for the prevention of severe infection after surgery. A
      series of antimicrobial and biocompatible tests have shown that the sandwich
      nanostructure with a low level of silver loading exhibits a bacteriostatic rate
      as high as 99.99%, while retaining low toxicity for cells and possessing high
      osteogenic potential. Titanium foil with a AgNP-filled hydrogen titanate nanotube
      layer on the surface that is fabricated with low-cost surface modification
      methods is a promising implantable material that will find applications in
      artificial bones, joints, and dental implants. 

PMID- 23966781
TI  - Self-microemulsifying drug delivery system for improved oral bioavailability of
      oleanolic acid: design and evaluation.
AB  - Oleanolic acid is a poorly water-soluble drug with low oral bioavailability. A
      self-microemulsifying drug delivery system (SMEDDS) has been developed to enhance
      the solubility and oral bioavailability of oleanolic acid. The formulation design
      was optimized by solubility assay, compatibility tests, and pseudoternary phase
      diagrams. The morphology, droplet size distribution, zeta potential, viscosity,
      electrical conductivity, and refractive index of a SMEDDS loaded with oleanolic
      acid were studied in detail. Compared with oleanolic acid solution, the in vitro
      release of oleanolic acid from SMEDDS showed that the drug could be released in a
      sustained manner. A highly selective and sensitive high-performance liquid
      chromatographymass spectrometry method was developed for determination of
      oleanolic acid in rat plasma. This method was used for a pharmacokinetic study of
      an oleanolic acid-loaded SMEDDS compared with the conventional tablet in rats.
      Promisingly, a 5.07-fold increase in oral bioavailability of oleanolic acid was
      achieved for the SMEDDS compared with the marketed product in tablet form. Our
      studies illustrate the potential use of a SMEDDS for delivery of oleanolic acid
      via the oral route. 

PMID- 23966782
TI  - Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation 1 as
      augmentation therapeutic strategy approaches in muscular dystrophy.
AB  - BACKGROUND: [Corrected] Muscular dystrophies consist of a number of juvenile and
      adult forms of complex disorders which generally cause weakness or efficiency
      defects affecting skeletal muscles or, in some kinds, other types of tissues in
      all parts of the body are vastly affected. In previous studies, it was observed
      that along with muscular dystrophy, immune inflammation was caused by
      inflammatory cells invasion - like T lymphocyte markers (CD8+/CD4+). Inflammatory
      processes play a major part in muscular fibrosis in muscular dystrophy patients.
      Additionally, a significant decrease in amounts of two myogenic recovery factors
      (myogenic differentation 1 [MyoD] and myogenin) in animal models was observed.
      The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T
      helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery
      activity in muscular cells justifies using it alongside this drug. METHODS: In
      this study, a nanolipodendrosome carrier as a drug delivery system was designed.
      The purpose of the system was to maximize the delivery and efficiency of the two
      drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents
      in muscular dystrophy phenotypic mice. The generation of new muscular cells was
      analyzed in SW1 mice. Then, immune system changes and probable side effects after
      injecting the nanodrug formulations were investigated. RESULTS: The loaded
      lipodendrimer nanocarrier with the candidate drug, in comparison with the
      nandrolone control drug, caused a significant increase in muscular mass, a
      reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was
      observed. The results support the hypothesis that the nanolipodendrimer
      containing the two candidate drugs will probably be an efficient means to
      ameliorate muscular degeneration, and warrants further investigation.

PMID- 23966783
TI  - Mental health system in Saudi Arabia: an overview.
AB  - BACKGROUND: There is evidence that mapping mental health systems (MHSs) helps in
      planning and developing mental health care services for users, families, and
      other caregivers. The General Administration of Mental Health and Social Services
      of the Ministry of Health over the past 4 years has sought to streamline the
      delivery of mental health care services to health consumers in Saudi Arabia.
      OBJECTIVE: We overview here the outcome of a survey that assessed the Saudi MHS
      and suggest strategic steps for its further improvement. METHOD: The World Health
      Organization Assessment Instrument for Mental Health Systems was used
      systematically to collect information on the Saudi MHS in 2009-2010, 4 years
      after a baseline assessment. RESULTS: Several mental health care milestones,
      especially provision of inpatient mental health services supported by a ratified
      Mental Health Act, were achieved during this period. However, community mental
      health care services are needed to match international trends evident in
      developed countries. Similarly, a larger well-trained mental health workforce is
      needed at all levels to meet the ever-increasing demand of Saudi society.
      CONCLUSION: This updated MHS information, discussed in light of international
      data, will help guide further development of the MHS in Saudi Arabia in the
      future, and other countries in the Eastern Mediterranean region may also benefit
      from Saudi experience.

PMID- 23966784
TI  - Facial expression in patients with bipolar disorder and schizophrenia in response
      to emotional stimuli: a partially shared cognitive and social deficit of the two
      disorders.
AB  - INTRODUCTION: It has recently been highlighted that patients affected by
      schizophrenia (SCZ) and those affected by bipolar disorder (BD) undergo gradual
      chronic worsening of cognitive and social functioning. The objective of the
      current study was to evaluate and compare (using the Facial Action Coding System
      [FACS]) the way by which patients with the two disorders experience and display
      emotions in relation to specific emotional stimuli. MATERIALS AND METHODS: Forty
      five individuals participated in the study: 15 SCZ patients, 15 BD patients, and
      15 healthy controls. All participants watched emotion-eliciting video clips while
      their facial activity was videotaped. The congruent/incongruent feeling of
      emotions and the facial expression in reaction to emotions were evaluated.
      RESULTS: SCZ and BD patients presented similar incongruent emotive feelings and
      facial expressions (significantly worse than healthy participants); SCZ patients
      expressed the emotion of disgust significantly less appropriately than BD
      patients. DISCUSSION: BD and SCZ patients seem to present a similar relevant
      impairment in both experiencing and displaying emotions; this impairment may be
      seen as a behavioral indicator of the deficit of social cognition present in both
      the disorders. As the disgust emotion is mainly elaborated in the insular cortex,
      the incongruent expression of disgust of SCZ patients can be interpreted as a
      further evidence of a functional deficit of the insular cortex in this disease.
      Specific remediation training could be used to improve emotion and social
      cognition in SCZ and BD patients.

PMID- 23966785
TI  - A new generation of antipsychotics: pharmacology and clinical utility of
      cariprazine in schizophrenia.
AB  - Cariprazine is a potential antipsychotic awaiting approval from the US Food and
      Drug Administration. It is a dopamine D2- and D3-receptor partial agonist, with
      higher affinity for D3 receptors, as opposed to the D2 antagonism of most older
      antipsychotic agents. Like most lipophilic antipsychotics, it undergoes extensive
      hepatic metabolism by cytochrome P450 (CYP), mainly the highly variable 3A4, with
      the formation of active metabolites. However, the parent compound - particularly
      its active didesmethyl derivative - is cleared very slowly, with elimination half
      lives in schizophrenic patients ranging from 2-5 days for cariprazine to 2-3
      weeks for didesmethyl-cariprazine. Exposure to the latter was several times that
      for cariprazine, although didesmethyl-cariprazine did not reach steady state
      within the 3 weeks of 12.5 mg/day dosing. Preliminary information on its
      therapeutic role comes from press releases and a few abstracts presented at
      scientific meetings. In short-term controlled trials, it was more effective than
      placebo in reducing positive and negative symptoms of schizophrenia, with an
      effective dose range of 1.5-12 mg/day. Although cariprazine was associated with a
      higher incidence of akathisia and extrapyramidal side effects than placebo, it
      did not cause weight gain, metabolic abnormalities, prolactin increase, or
      corrected QT prolongation. Similarly, cariprazine's efficacy and tolerability for
      the treatment of bipolar disorder (manic/mixed and depressive episodes) was
      established in the dose range of 3-12 mg/day, although again no long-term data
      are available. Well-designed clinical trials, mainly direct "head-to-head"
      comparisons with other second-generation antipsychotic agents, are needed to
      define the therapeutic role and safety profile of cariprazine in schizophrenia
      and bipolar mania. 

PMID- 23966786
TI  - Vacuum-venipuncture skills: time required and importance of tube order.
AB  - BACKGROUND: The purpose of this study was to assess specific vacuum-venipuncture
      skills and the influence of the time involved in skin puncture and blood
      collection. METHODS: Thirty subjects undergoing venipuncture in which video
      analysis was possible were included. These procedures were carried out by four
      nurses and recorded with a digital camera. Venipuncture skills classified by our
      observations were delineated on the basis of frame-by-frame video images, and a
      graph of x and y coordinates was created. RESULTS: With the first blood
      collection tube, strong blood flow required the practitioner to push the tube
      back in to compensate for the strong repulsive force in approximately 46% of
      cases. By the third blood-collection tube, the blood flow had weakened;
      therefore, the tube was moved up and down. In cases that required a second
      venipuncture, the tube was already pierced, so the time required to fill it to 5
      mL was significantly longer. CONCLUSION: Hand movement of the practitioner is
      adjusted according to blood flow. Reflex movement in response to strong blood
      flow may increase the risk of pushing the needle through the vein with excessive
      force. The time required to fill the tube varies among nurses, tube order, and
      level of venipuncture skills.

PMID- 23966787
TI  - Antioxidant Supplements Improve Profiles of Hepatic Oxysterols and Plasma Lipids
      in Butter-fed Hamsters.
AB  - Hypercholesterolemic diets are associated with oxidative stress that may
      contribute to hypercholesterolemia by adversely affecting enzymatically-generated
      oxysterols involved in cholesterol homeostasis. An experiment was conducted to
      examine whether the cholesterol-lowering effects of the antioxidants selenium and
      alpha-tocopherol were related to hepatic oxysterol concentrations. Four groups of
      male Syrian hamsters (n = 7-8) were fed high cholesterol and saturated fat (0.46%
      cholesterol, 14.3% fat) hypercholesterolemic semi-purified diets: 1) Control; 2)
      Control + alpha-tocopherol (67 IU all-racemic-alpha-tocopheryl-acetate/kg diet);
      3) Control + selenium (3.4 mg selenate/kg diet); and 4) Control + alpha
      tocopherol + selenium. Antioxidant supplementation was associated with lowered
      plasma cholesterol concentrations, decreased tissue lipid peroxidation and higher
      hepatic oxysterol concentrations. A second experiment examined the effect of
      graded selenium doses (0.15, 0.85, 1.7 and 3.4 mg selenate/kg diet) on mRNA
      expression of the oxysterol-generating enzyme, hepatic 27-hydroxylase (CYP27A1,
      EC 1.14.13.15), in hamsters (n = 8-9) fed the hypercholesterolemic diets.
      Supplementation of selenium at 3.4 mg selenate/kg diet was not associated with
      increased hepatic 27-hydroxylase mRNA. In conclusion, the cholesterol lowering
      effects of selenium and alpha-tocopherol were associated with increased hepatic
      enzymatically generated oxysterol concentrations, which appears to be mediated
      via improved antioxidant status rather than increased enzymatic production. 

PMID- 23966788
TI  - Effect of the DASH Diet on Pre- and Stage 1 Hypertensive Individuals in a Free
      Living Environment.
AB  - BACKGROUND: Dietary Approaches to Stop Hypertension (DASH) has been shown to
      successfully reduce systolic (SBP) and diastolic blood pressure (DBP) when
      evaluated in clinically controlled environments but there is a lack of
      information regarding the efficacy of the original DASH diet when it is applied
      in a free-living environment. PURPOSE: To provide descriptive data as to the
      changes in blood pressure individuals could expect to achieve when following the
      DASH diet in a free-living environment for 4-weeks with no additional behavioral
      modifications. METHODS: Twenty, pre- and stage 1 hypertensive participants were
      randomly split into 2 groups; DASH (males N = 5, females N = 5, age = 38.5 +/-
      10.8) and control (males N = 7, females N = 3, age = 38.1 +/- 11.1). The DASH
      group was instructed on how to follow the DASH diet on their own for 4-weeks
      while the control group continued their normal diet. SBP, DBP, body weight, 3-day
      food diaries and physical activity recall questionnaire data were collected pre
      and post intervention using a traditional person-to-person instructional
      technique. RESULTS: Two-way ANOVA demonstrated that there was a significant group
      (DASH, control) by time (pre, post) interaction for SBP (P = 0.003) and no
      significant effects for DBP. The interaction was due to a significant reduction
      (P < 0.001) in SBP in the DASH group (pre: 141.3 +/- 11.3 mmHg vs. post: 130.7 +/
      9.1 mmHg) over the course of the intervention with no change in SBP in the
      control group (pre: 133.5 +/- 6.6 mmHg vs. post: 131.9 +/- 8.9 mmHg). Pearson's
      correlation analyses revealed that changes in potential moderators of blood
      pressure including body weight, BMI, sodium intake and total kilocalories were
      each not associated with changes in SBP (r <= 0.14, P >= 0.5) or DBP (r <= 0.10,
      P >= 0.6) pre- to post-treatment. Chi-square demonstrated no significant
      differences in the number of participants per group (n = 4 DASH, n = 1 control)
      who indicated increasing physical activity during the intervention. CONCLUSION:
      DASH diet followed in a free-living environment significantly reduced SBP but not
      DBP. However, the changes in SBP and DBP were very similar to those noted in
      controlled clinical feeding evaluations of the DASH diet. Presently, none of the
      potential moderators of blood pressure that were assessed were independently
      associated with the observed changes in blood pressure which may be due to our
      small sample size or the possibility that it is the combined change in multiple
      factors that lead to reductions in blood pressure when following the DASH diet.

PMID- 23966789
TI  - Effect of nutritional supplements on immune function and body weight in
      malnourished adults.
AB  - In the United States, approximately 5% of the population is malnourished or has
      low body weight, which can adversely affect immune function. Malnutrition is more
      prevalent in older adults and is often a result of energy imbalance from various
      causes. Dietary supplementation to promote positive energy balance can reverse
      malnutrition, but has not been assessed for its effect on immune parameters. This
      8-week clinical feeding trial evaluated the effect of a commercially available,
      high-protein, high-energy formula on body weight and immune parameters in 30
      adult volunteers with body-mass indices (BMI) <21 kg/m(2). After the
      intervention, participants gained a mean of 3.74 lbs and increased BMI by 0.58
      kg/m(2). The intervention improved lean body mass and limited body fat
      accumulation. However, no clinically significant improvements in immune measures
      were observed. These results support the use of high-protein, high-energy
      supplements in the treatment of underweight/malnutrition. Further investigation
      utilizing feeding studies of longer duration, and/or studying severely
      malnourished individuals may be needed to detect an effect on immune parameters
      of weight gain promoted by nutritional supplements. 

PMID- 23966790
TI  - Increased Serum Cu/Zn SOD in Individuals with Clinical Depression Normalizes
      After Zinc and Anti-oxidant Therapy.
AB  - AIM: To assess serum Cu/Zn SOD (Superoxide Dismutase) concentration in
      individuals with clinical depression. SUBJECTS AND METHODS: Serum from 36
      individuals diagnosed with clinical depression and 18 healthy controls were
      tested for Cu/Zn SOD serum concentration using ELISAs. RESULTS: Serum Cu/Zn SOD
      levels of depressed individuals (both with and without secondary anxiety) were
      significantly higher than age and gender similar controls. We also found that,
      post anti-oxidant therapy, Cu/Zn SOD levels normalized to the level of normal
      healthy controls. DISCUSSION: These results suggest an association between Cu/Zn
      SOD serum levels and clinical depression.

PMID- 23966791
TI  - Decreased Serum Hepatocyte Growth Factor (HGF) in Individuals with Anxiety
      Increases After Zinc Therapy.
AB  - AIM: To assess serum Hepatocyte Growth Factor (HGF) levels in individuals with
      anxiety and to test the hypothesis that there is a relationship between HGF
      levels and zinc therapy. SUBJECTS AND METHODS: Serum from 19 individuals with
      anxiety and 19 controls were tested for serum HGF using ELISAs. HGF serum
      concentration in individuals with anxiety before zinc and anti-oxidant therapy
      was compared to levels after therapy. Zinc and copper levels in anxiety patients,
      pre and post therapy, were also measured and compared. RESULTS: Individuals with
      anxiety had significantly lower serum levels of HGF compared to controls (P =
      0.0005). HGF concentration rose significantly (normalized) after zinc therapy (P
      = 0.04) and zinc levels increased significantly in these same patients (P =
      0.0002). DISCUSSION: These results suggest an association between HGF serum
      levels and individuals with anxiety and demonstrate that zinc therapy is
      associated with increasing HGF levels.

PMID- 23966792
TI  - Single nucleotide polymorphisms in the mitochondrial displacement loop and age at
      onset of non-Hodgkin lymphoma.
AB  - OBJECTIVE: Single nucleotide polymorphisms (SNPs) accumulated frequently in the
      mitochondrial displacement loop (D-loop) in many cancers. We had identified
      cancer risk-associated SNPs in the D-loop of non-Hodgkin lymphoma (NHL) patients
      previously, in this study, we investigated the association of age at onset and D
      loop SNPs in NHL patients. MATERIALS AND METHODS: The D-loop region of mtDNA was
      sequenced for 133 NHL patients recorded at the Fourth Hospital of Hebei Medical
      University. The Kaplan-Meier method was used to identify age at onset-associated
      SNPs in the D-loop of NHL patients. The Cox proportional hazards model was used
      to identify independent risk factors for age at onset. RESULTS: The SNP sites of
      nucleotides 146C/T, 151T/C, 194T/C, 315C/C insert, 523Del/A, and 525Del/C were
      identified for their association with age at onset, by the logrank test. In an
      overall multivariate analysis, allele 146 (relative risk, 0.403; 95% confidence
      interval [CI]: 0.182-0.895) (P = 0.026), allele 151 (relative risk, 0.378; 95%
      CI: 0.165-0.868) (P = 0.022), and allele 315 (relative risk, 3.554; 95% CI: 1.344
      9.400) (P = 0.011) were identified as independent predictors for age at onset in
      NHL patients. CONCLUSION: SNPs in the D-loop can predict age at onset in NHL
      patients. Analysis of the D-loop SNPs can help identify NHL patient subgroups at
      high risk of early onset.

PMID- 23966793
TI  - Adjuvant chemotherapy for luminal A breast cancer: a prospective study comparing
      two popular chemotherapy regimens.
AB  - INTRODUCTION: Based on the variable benefit of taxanes in the adjuvant setting of
      early breast cancer in certain tumor phenotypes, especially in human epidermal
      growth factor receptor (HER)2-positive and triple-negative disease, and with the
      observation of a lesser benefit in luminal A, this research article aimed at
      exploring the value of docetaxel in patients with an estrogen receptor-positive,
      HER2-negative disease phenotype, who might not derive the same benefits as those
      with other phenotypes. PATIENTS AND METHODS: This was a randomized prospective
      study comparing disease-free survival (DFS) and safety profile of sequential
      adjuvant three cycles Fluorouracil, Epirubicin, Cyclophosphamide followed by
      three cycles Docetaxel (FEC-D) versus six cycles classic Fluorouracil,
      Epirubicin, Cyclophosphamide (FEC)-100 in 60 Egyptian women who presented to Dar
      Al Fouad Hospital during the period June 2007 to July 2008 with (pT1-2 pN0-3 M0).
      The primary end point was DFS in a follow-up period of 4 years. The secondary end
      point was toxicity profile. RESULTS: Four-year DFS rates were comparable in both
      arms: 73.3% +/- 8.1% in the FEC-D arm versus 76.5% +/- 7.8% in the FEC-100 arm (P
      = 0.83). N3 and grade III subgroups achieved the worst DFS in both subgroups (P =
      0.001 and P = 0.214, respectively). The rate of nausea and vomiting was higher in
      the FEC-100 arm (P = 0.49), while grade III-IV neutropenia and febrile
      neutropenia incidence was similar between both arms. CONCLUSION: Sequential
      adjuvant chemotherapy with FEC followed by docetaxel achieved comparable DFS
      results to FEC alone in luminal A phenotype subgroups of breast cancer.

PMID- 23966795
TI  - Effects of two inhaled corticosteroid/long-acting beta-agonist combinations on
      small-airway dysfunction in mild asthmatics measured by impulse oscillometry.
AB  - BACKGROUND: We previously showed that the long-acting beta agonist (LABA)
      salmeterol as inhalation powder or metered-dose inhaler improves lung-function
      parameters assessed by impulse oscillometry (IOS) in 2- to 5-year-old children
      with reversible-airway disease within 15 minutes. OBJECTIVE: We studied 12- to 45
      year-olds with mild persistent asthma in order to compare the onset and extent of
      peripheral airway effects following the first dose and after 4 weeks dosing with
      two inhaled corticosteroid (ICS)/LABA combinations: fluticasone
      propionate/salmeterol 115/21 and budesonide/formoterol 160/4.5. METHODS: Thirty
      subjects with mild persistent asthma using only an as-needed short-acting beta
      agonist (albuterol) who had at least a 40% change in integrated low-frequency
      reactance postalbuterol were selected and randomized to receive either
      fluticasone propionate/salmeterol or budesonide/formoterol (15 subjects each). We
      collected three to six IOS replicates at baseline, at 5, 20, 40, 60, 120, and 240
      minutes postdose at randomization, and after 4 weeks of twice-daily dosing.
      Blinded investigators calculated IOS frequency-dependent resistance and reactance
      (R5-R20 and AX), indicative of small-airway dysfunction, and also estimated the
      peripheral airway resistance (Rp ) and peripheral airway compliance (Cp ), using
      a respiratory-impedance model. RESULTS: At randomization visits, onset of action
      was detected as early as 5 minutes (t-test, P < 0.05) after fluticasone
      propionate/salmeterol by Cp , and within 5 minutes after budesonide/formoterol by
      R5-R20, AX, Rp , and Cp . However, after 4 weeks of dosing, only Rp was
      significantly different (from 60 to 120 minutes) after fluticasone
      propionate/salmeterol, while R5-R20, AX, Rp , and Cp were not significantly
      different within 240 minutes after budesonide/formoterol. CONCLUSION: These two
      ICS/LABA combinations initially improved the peripheral airway function of 12- to
      45-year-old asthmatics significantly in about 5 minutes or less, as measured by
      R5-R20, AX, Rp , and/or Cp . After regular dosing for 4 weeks, pre- to postdose
      differences in these parameters had diminished significantly due to improved
      predose status of peripheral airways. Single dosing with ICS/LABA combinations in
      mild persistent asthma improves small-airway function, and the effect is
      maintained over a 12-hour interval by regular use for 4 weeks.

PMID- 23966796
TI  - Streptococcus group C meningitis with cavernous sinus thrombosis.
AB  - Group C Streptococcus (GCS) is a rare cause of bacteremia in humans. It is mostly
      associated with zoonological infections. Although GCS can be part of the normal
      oral, skin, and genitourinary fora, an infection with this pathogen can be highly
      virulent, causing rapid, disseminating disease. With a mortality of about 25%,
      the poor prognosis is linked to the severity of illness and the high level of
      virulence of the organism. Only a few cases of GCS meningitis have been reported.
      We present the first case of GCS meningitis with cavernous sinus thrombosis. 

PMID- 23966797
TI  - Procalcitonin as a useful marker to decide upon intervention for urinary tract
      infection.
AB  - BACKGROUND: Because the use of procalcitonin has been advocated as a marker of
      bacterial infection, this study was carried out to determine the usefulness of
      serum PCT as an early marker to decide upon intervention for urinary tract
      infection. METHODS: The subjects were 68 patients with urinary tract infection
      (UTI) in whom we measured serum procalcitonin concentration at the start of
      treatment. RESULTS: There were 47 patients with nonobstructed UTI and 21 with
      obstructed UTI. All patients with obstructed UTI were subjected to intervention.
      There were significant differences in procalcitonin, white blood cells, and
      creatinine levels between patients with nonobstructed and obstructed UTI (P <
      0.05). CONCLUSION: Although this retrospective study comprised a small number of
      patients, we found that procalcitonin was a useful marker to decide upon urinary
      intervention.

PMID- 23966794
TI  - Combining molecular targeted agents with radiation therapy for malignant gliomas.
AB  - The expansion in understanding the molecular biology that characterizes cancer
      cells has led to the rapid development of new agents to target important
      molecular pathways associated with aberrant activation or suppression of cellular
      signal transduction pathways involved in gliomagenesis, including epidermal
      growth factor receptor, vascular endothelial growth factor receptor, mammalian
      target of rapamycin, and integrins signaling pathways. The use of antiangiogenic
      agent bevacizumab, epidermal growth factor receptor tyrosine kinase inhibitors
      gefitinib and erlotinib, mammalian target of rapamycin inhibitors temsirolimus
      and everolimus, and integrin inhibitor cilengitide, in combination with radiation
      therapy, has been supported by encouraging preclinical data, resulting in a rapid
      translation into clinical trials. Currently, the majority of published clinical
      studies on the use of these agents in combination with radiation and cytotoxic
      therapies have shown only modest survival benefits at best. Tumor heterogeneity
      and genetic instability may, at least in part, explain the poor results observed
      with a single-target approach. Much remains to be learned regarding the optimal
      combination of targeted agents with conventional chemoradiation, including the
      use of multipathways-targeted therapies, the selection of patients who may
      benefit from combined treatments based on molecular biomarkers, and the
      verification of effective blockade of signaling pathways. 

PMID- 23966798
TI  - Economic evaluation of highly purified human menopausal gonadotropin versus
      recombinant human follicle-stimulating hormone in fresh and frozen in vitro
      fertilization/intracytoplasmic sperm-injection cycles in Sweden.
AB  - Gonadotropin-releasing hormone-analog type, fertilization method, and number of
      embryos available for cryopreservation should be incorporated into economic
      evaluations of highly purified human menopausal gonadotropin (HP-hMG) and
      recombinant human follicle-stimulating hormone (r-hFSH), as they may affect
      treatment costs. We searched for randomized trials and meta-analyses comparing HP
      hMG and r-hFSH. Meta-analysis showed no significant difference in live births
      (odds ratio 0.82, 95% confidence interval [CI] 0.66-1.01), but a greater number
      of oocytes with r-hFSH (mean difference [MD] 1.96, 95% CI 1.02-2.90). Using a
      cost-minimization model for Sweden, accounting for embryo availability, survival
      following thawing, and patient dropout, we simulated patients individually for up
      to three cycles. R-hFSH was found to be cost-saving, at 2,767 kr (95% CI 1,580
      4,057) per patient (?315 or $411); baseline savings were 6.43% of the total HP
      hMG cost. In fresh cycles only, the savings for r-hFSH were 1,752 kr (95% CI 48
      3,658) per patient (?200 or $260). In univariate sensitivity analyses, savings
      were obtained until the price of r-hFSH increased by 30% or the dosage of HP-hMG
      decreased by 38%-62% of baseline value. In probabilistic sensitivity analysis, r
      hFSH was cost-saving in 100% of the simulated cohort per patient and in 85% per
      live birth; the respective percentages for fresh cycles only were 97.3% and
      73.1%. In conclusion, a greater number of oocytes with r-hFSH allows for more
      frozen embryo transfers, thereby reducing overall treatment cost. 

PMID- 23966799
TI  - Impact of scribes on patient interaction, productivity, and revenue in a
      cardiology clinic: a prospective study.
AB  - OBJECTIVE: Scribes have been used in the emergency department to improve
      physician productivity and patient interaction. There are no controlled,
      prospective studies of scribe use in the clinic setting. METHODS: A prospective
      controlled study compared standard visits (20 minute follow-up and 40 minute new
      patient) to a scribe system (15 minute follow-up and 30 minute new patient) in a
      cardiology clinic. Physician productivity, patient satisfaction, physician
      patient interaction, and revenue were measured. RESULTS: Four physicians saw 129
      patients using standard care and 210 patients with scribes during 65 clinic hours
      each. Patients seen per hour increased (P < 0.001) from 2.2 +/- 0.3 to 3.5 +/-
      0.4 (59% increase) and work relative value units (wRVU) per hour increased (P <
      0.001) from 3.5 +/- 1.3 to 5.5 +/- 1.3 (57% increase). Patient satisfaction was
      high at baseline and unchanged with scribes. In a substudy, direct patient
      contact time was lower (9.1 +/- 2.0 versus 12.9 +/- 3.4 minutes; P < 0.01) for
      scribe visits, but time of patient interaction (without computer) was greater
      (6.7 +/- 2.1 versus 1.5 +/- 1.9 minutes; P < 0.01). Subjective assessment of
      physician-patient interaction (1-10) was higher (P < 0.01) on scribe visits (9.1
      +/- 0.9 versus 7.9 +/- 1.1). Direct and indirect (downstream) revenue per patient
      seen was $142 and $2,398, with $205,740 additional revenue generated from the 81
      additional patients seen with scribes. CONCLUSION: Using scribes in a cardiology
      clinic is feasible, produces improvements in physician-patient interaction, and
      results in large increases in physician productivity and system cardiovascular
      revenue.

PMID- 23966800
TI  - Warfarin-induced calciphylaxis: a case report and review of literature.
AB  - Calciphylaxis is a challenging complication of end-stage renal disease, with an
      unknown underlying mechanism. Several risk factors have been identified, such as
      hyperphosphatemia, hypercalcemia, hyperparathyroidism, low serum albumin levels,
      and history of warfarin therapy. This article presents a case of calciphylaxis
      provoked by reintroduction of warfarin therapy, introducing the possibility of
      direct induction. 

PMID- 23966802
TI  - Management of osteoporosis and menopausal symptoms: focus on
      bazedoxifene/conjugated estrogen combination.
AB  - Loss of estrogen production in women during menopause results in a state of
      estrogen deficiency which has been associated with multiple problems, including
      vasomotor symptoms, symptoms of vulvovaginal atrophy, bone loss, and difficulties
      with sleep, mood, memory, and sexual activity. The only treatment option
      currently available to address multiple postmenopausal symptoms in women with an
      intact uterus is estrogen/progestin-containing hormone therapy (HT). Concerns
      surrounding side effects and published data regarding the association of HT with
      the increased risk for breast cancer have induced a decrease in the number of
      women seeking, initiating, and continuing this type of therapy. A combination
      containing bazedoxifene and conjugated estrogens (BZA/CE) maintains the
      established benefits of estrogen therapy for treatment of postmenopausal
      vasomotor symptoms, vulvovaginal atrophy, and osteoporosis, while certain
      estrogenic effects, such as stimulation of the uterus and breast, are antagonized
      without the side effects associated with HT. BZA/CE has been evaluated in a
      series of multicenter, randomized, double-blind, placebo-controlled, and active
      controlled Phase III trials known as the Selective estrogens, Menopause, And
      Response to Therapy (SMART) trials. BZA/CE demonstrated clinically meaningful
      improvements in vasomotor symptoms, vulvovaginal atrophy, and a protective effect
      on the skeleton. These clinical benefits were associated with an acceptable
      safety profile and an improved tolerability compared with HT. BZA/CE showed a
      favorable safety profile on the breast, endometrium, and ovaries. The incidence
      of venous thromboembolism was low and the risk does not appear to be any greater
      than for CE alone or BZA alone or greater than HT. The incidence of coronary
      heart disease and cerebrovascular accidents were similar to placebo. The overall
      incidence of cancer (including breast cancer) was low and similar to placebo. The
      SMART trials demonstrate that BZA/CE is an alternative option for treating non
      hysterectomized, symptomatic, postmenopausal women. 

PMID- 23966801
TI  - Existing data sources for clinical epidemiology: Danish registries for studies of
      medical genetic diseases.
AB  - Denmark has an extensive collection of national and regional medical registries.
      There are many advantages to registry-based research when investigating genetic
      diseases which, due to their rarity, can be difficult to identify. In this study,
      we aimed to provide an updated overview of Danish registries for medical genetic
      conditions and describe how data linkage across registries can be used to collect
      data on genetic diseases at the individual level and at the family level. We
      present a list of medical genetic registries in Denmark at the national level,
      data sources from the departments of clinical genetics and other specialized
      centers, and project-specific data sources. We also summarize key general
      registries, such as the Danish National Registry of Patients, the Danish Medical
      Birth Registry, and the Civil Registration System, which are renowned for their
      comprehensive and high quality data, and are useful supplemental data sources for
      genetic epidemiology research. We describe the potential for data linkage across
      multiple registries, which allows for access to medical histories with follow-up
      time spanning birth to death. Finally, we provide a brief introduction to the
      Danish epidemiological research setting and legalities related to data access.
      The Danish collection of medical registries is a valuable resource for genetic
      epidemiology research. 

PMID- 23966803
TI  - Resolution of exudative retinal detachment and regression of retinal macrocyst
      post-laser in Coats disease.
AB  - A 15-year-old boy presented with painless progressive blurring of vision in the
      right eye for 1 year in duration. His visual acuity in the right eye was hand
      movement. The right fundus showed presence of extensive subretinal exudates at
      the posterior pole and a retinal macrocyst at the temporal periphery. It was
      associated with exudative retinal detachment at the inferior periphery of the
      retina. Fundus angiography revealed telangiectatic retinal vessels at the
      superotemporal retina. Based on clinical and angiographic findings, a diagnosis
      of Coats disease was made. He was treated with retinal laser photocoagulation.
      There was resolution of the exudative retinal detachment, reduction of subretinal
      exudates, and regression of the retinal macrocyst with improvement of visual
      acuity to 1/60 post-laser therapy. 

PMID- 23966804
TI  - MEchatronic REspiratory System SImulator for Neonatal Applications (MERESSINA)
      project: a novel bioengineering goal.
AB  - Respiratory function is mandatory for extrauterine life, but is sometimes
      impaired in newborns due to prematurity, congenital malformations, or acquired
      pathologies. Mechanical ventilation is standard care, but long-term
      complications, such as bronchopulmonary dysplasia, are still largely reported.
      Therefore, continuous medical education is mandatory to correctly manage devices
      for assistance. Commercially available breathing function simulators are rarely
      suitable for the anatomical and physiological realities. The aim of this study is
      to develop a high-fidelity mechatronic simulator of neonatal airways and lungs
      for staff training and mechanical ventilator testing. The project is divided into
      three different phases: (1) a review study on respiratory physiology and
      pathophysiology and on already available single and multi-compartment models; (2)
      the prototyping phase; and (3) the on-field system validation. 

PMID- 23966805
TI  - Deferasirox: appraisal of safety and efficacy in long-term therapy.
AB  - Deferasirox is a once-daily, oral iron chelator that is widely used in the
      management of patients with transfusional hemosiderosis. Several Phase II trials
      along with their respective extension studies as well as a Phase III trial have
      established the efficacy and safety of this novel agent in transfusion-dependent
      patients with beta-thalassemia, sickle-cell disease and bone marrow-failure
      syndromes, including myelodysplastic syndrome and aplastic anemia. Data from
      various clinical trials show that a deferasirox dose of 20 mg/kg/day stabilizes
      serum ferritin levels and liver iron concentration, while a dose of 30-40
      mg/kg/day reduces these parameters and achieves negative iron balance in red cell
      transfusion-dependent patients with iron overload. Across various pivotal
      clinical trials, deferasirox was well tolerated, with the most common adverse
      events being gastrointestinal disturbances, skin rash, nonprogressive increases
      in serum creatinine, and elevations in liver enzyme levels. Longer-term extension
      studies have also confirmed the efficacy and safety of deferasirox. However, it
      is essential that patients on deferasirox therapy are monitored regularly to
      ensure timely management for any adverse events that may occur with long-term
      therapy. 

PMID- 23966806
TI  - Serum prolidase activity in ankylosing spondylitis and rheumatoid arthritis.
AB  - The aim of the present study was to emphasize the collagen turnover in 2 of the
      most common chronic inflammatory rheumatic diseases by evaluating serum prolidase
      activity (SPA) in ankylosing spondylitis (AS) and rheumatoid arthritis (RA). 30
      patients who met the modified New York Criteria for the classification of AS, 29
      patients who met the 2010 Rheumatoid Arthritis Classification Criteria for the
      classification of RA, and 31 healthy controls were enrolled in the study. Serum
      samples of the patients and the controls were collected and SPA was measured by a
      spectrophotometric method. The comparison of the SPA in these 3 groups was
      statistically examined. In both patient groups, the SPA was lower than in the
      control group. SPA in patients with AS was statistically significantly lower than
      in the control and RA groups (P < 0.001/P = 0.002). No statistically significant
      difference was found between the RA and the control groups (P = 0.891). In
      conclusion, lower SPA is presumably associated with decreased collagen turnover
      and fibrosis, leading to decreased physical functions in both chronic
      inflammatory musculoskeletal diseases. 

PMID- 23966807
TI  - Serum cystatin C and tubular urinary enzymes as biomarkers of renal dysfunction
      in type 2 diabetes mellitus.
AB  - Renal tubulointerstitium plays an important role in the development and
      progression of diabetic nephropathy. The aim of this study was to assess serum
      cystatin C and 2 renal tubular enzymes, neutrophil gelatinase associated
      lipocalin (NGAL) and N-acetyl-beta-D-glucosaminidase (NAG), as screening markers
      for early renal dysfunction in patients with type 2 diabetes mellitus (T2DM). ROC
      curve analysis showed that urinary NAG is the most sensitive marker of
      microalbuminuria and early renal damage with sensitivity of 83.3%, while serum
      cystatin C was the most sensitive and specific marker of macroalbuminuria and
      damage progress with sensitivity of 70.8% and specificity of 83.3% versus 70.6%
      and 83.3% for uNGAL; and 64.7% and 66.7% for NAG, respectively. Our data indicate
      that urinary NAG is the most sensitive marker for early renal damage in diabetic
      patients. However, for damage progress, serum cystatin C is the most sensitive
      and specific marker for follow-up and monitoring renal dysfunction. 

PMID- 23966808
TI  - Saxagliptin and metformin in fixed combination for the treatment of type 2
      diabetes in adults.
AB  - Type 2 diabetes affects millions of people worldwide and significantly
      contributes to morbidity and mortality of those affected by it. Current
      guidelines recommend individualized treatment regimens following first line
      metformin therapy. Saxagliptin, a dipeptidyl-peptidase 4 inhibitor, provides a
      secondary mechanism of action to decrease hyperglycemia when used in combination
      with metformin. The combination of metformin and saxagliptin has shown
      improvements in hemoglobin A1c and fasting plasma glucose in greater efficacy
      than when either agent is used alone. Adverse effects of combination therapy are
      similar to when these agents are used individually, and are rated as tolerable by
      patient satisfaction scores. Overall, the combination use of saxagliptin in
      addition to metformin is an attractive option for clinicians to use in the
      treatment of type 2 diabetes. 

PMID- 23966809
TI  - Treatment of childhood psoriasis with phototherapy and photochemotherapy.
AB  - Phototherapy and photochemotherapy are well-described treatment modalities for
      psoriasis in adults. Like many other treatments, the experience and long-term
      safety of their use in children is limited. We conducted a literature search and
      identified publications reporting the use of phototherapy and photochemotherapy
      in pediatric populations. This article summarizes the existing literature on this
      topic. Although many studies report good improvement with these treatment
      modalities, long-term safety data on their use is lacking for pediatric patients.

PMID- 23966810
TI  - Alkalizer administration improves renal function in hyperuricemia associated with
      obesity.
AB  - We evaluated the combination effect of the alkalizer citrate with the xanthine
      oxidase inhibitor allopurinol on renal function and uric acid in patients with
      hyperuricemia associated with obesity and/or metabolic syndrome (MetS), who were
      extracted from among the subjects enrolled in a prospective randomized controlled
      study aimed at assessing the efficacy of such a combination for improving renal
      function. We also conducted a post hoc analysis to examine influences on lipid
      profiles. Patients who consented to participate in the study were randomly
      allocated to receive either allopurinol alone (monotherapy) or in combination
      with a citrate preparation (combination therapy). The analysis population
      consisted of 31 obese patients with a body mass index greater than 25 kg/m(2)
      (monotherapy, 15 patients; combination therapy, 16 patients). The creatinine
      clearance rate (Ccr), serum uric acid levels, and lipid profiles were measured
      before and at 12 weeks after the start of treatment. In the combination therapy
      group, Ccr increased significantly and serum uric acid levels decreased
      significantly in obese patients, while Ccr tended to increase and serum uric acid
      levels decreased, though not significantly, in patients with MetS-related
      clinical parameters. Overall, blood triglyceride levels tended to improve in the
      combination therapy group as compared with the monotherapy group. 

PMID- 23966811
TI  - A Case-Control Study of Esomeprazole Plus Rebamipide vs. Omeprazole Plus
      Rebamipide on Post-ESD Gastric Ulcers.
AB  - OBJECTIVES: Endoscopic submucosal dissection (ESD) is useful for treating gastric
      tumors. Several trials have shown the efficacy of 4 or 8 weeks of proton pump
      inhibitor (PPI) administration for post-ESD ulcers. However, if the size of the
      post-ESD ulcer is larger than predicted, PPI administration alone might not be
      sufficient for the ulcer to heal within 4 weeks. There is no report about the
      efficacy of post-ESD gastric ulcers by esomeprazole. We examined retrospectively
      the efficacy of a combination therapy of esomeprazole plus rebamipide, a mucosal
      protective antiulcer drug, on the acceleration of post-ESD ulcer healing
      comparing with omeprazole plus rebamipide. METHODS: We reviewed the medical
      records of patients who underwent ESD for gastric neoplasia. We conducted a case
      control study to compare the healing rates within 4 weeks effected by
      esomeprazole plus rebamipide (group E) and omeprazole plus rebamipide (group O).
      The sizes of the artificial ulcers were divided into normal-sized or large-sized.
      RESULTS: The baseline characteristics did not differ significantly between the
      two groups except age and sex. Stage S1 disease was observed in 27.6% and 38.7%
      of patients after 4 weeks of treatment in the group E and O, respectively. In
      large-sized artificial ulcers, the healing rate of stage S1 in group E is
      significantly higher than that in group O in 4 weeks.(25% VS 0%:P = 0.02).
      CONCLUSIONS: The safety and efficacy profiles of esomeprazole plus rebamipide and
      omeprazole and rebamipide are similar for the treatment of ESD-induced ulcers. In
      large-sized ulcers, esomeprazole plus rebamipide promotes ulcer healing.

PMID- 23966812
TI  - Smoking counteracts the favorable effect of exercise training on endothelial
      function in patients with type 2 diabetes.
AB  - BACKGROUND: Exercise training can improve endothelial function in patients with
      diabetes. We hypothesized that the favorable effect of exercise training on
      endothelial function in patients with diabetes is counteracted by cigarette
      smoking. PURPOSE: To assess whether there is a difference in the effect of
      exercise on endothelial function in smokers and non-smokers with type 2 diabetes.
      METHODS: We performed a 3-month controlled trial in 27 never-smoking and 17
      smoking individuals with type 2 diabetes who participated in a home-based walking
      program. The percentage decrease in post-exercise ankle-brachial pressure index
      (ABI), which is an index of endothelial function, was assessed at baseline and
      after 3 months. RESULTS: Compared to the smoking group, the never-smoking group
      showed a more significant improvement in post exercise ABI during the 3 months of
      home-based training (interaction, P < 0.01). CONCLUSIONS: These results indicate
      that smoking may counteract the favorable effects of exercise training on
      endothelial function. Endothelial function plays an important role in the
      prevention of cardiovascular disease among patients with diabetes. Therefore, a
      Certified Diabetes Educator should strongly advise diabetic patients not to
      smoke.

PMID- 23966813
TI  - Pregnancy complicated by cervical varix and low-lying placenta: a case report.
AB  - We present a case of cervical varix and low-lying placenta. A cesarean section
      was performed because of the risk of bleeding with vaginal delivery; hemostasis
      was achieved using z sutures at the bleeding points. After delivery, the cervical
      varix decreased dramatically in size. It is important to recognize the clinical
      features and available treatments for cervical varix. 

PMID- 23966814
TI  - Pathological findings in a case of failed uterine artery embolization for
      placenta previa.
AB  - The reported success rate of uterine artery embolization (UAE) for obstetrical
      hemorrhage is more than 90%. We experienced a case of failed UAE for postpartum
      hemorrhage, although an embolic particle was found pathologically in the uterine
      vessels without coagulation. A 42-year-old woman (gravida 7, para 2) with
      placenta previa had genital bleeding at 35 weeks of gestation, and cesarean
      section was performed. We immediately added UAE aiming to reduce massive bleeding
      after the cesarean section, successful embolization of the bilateral uterine
      arteries and internal iliac arteries were confirmed by angiography regardless the
      vital sign was recovered with an appropriate amount of transfusion; the massive
      bleeding recurred after 1 hour of UAE. Hysterectomy was performed and
      pathological findings of the uterus showed that there was no coagulation in the
      vessels, which was supposed to be observed by the effect of gelatin sponge. In
      addition, despite the fact that no coagulation was found, only one gelatin sponge
      was found in 16 slices of the uterine wall specimens. We speculate that
      thrombotic materials were caught in vasoconstricted vessels triggered by
      hypovolemic shock due to acute blood loss, and then the gelatin sponge could be
      washed out after recovering to normalized circulation status leading to recurrent
      massive hemorrhage. 

PMID- 23966815
TI  - Hereditary Disorders with Defective Repair of UV-Induced DNA Damage.
AB  - Nucleotide excision repair (NER) is an essential system for correcting
      ultraviolet (UV)-induced DNA damage. Lesions remaining in DNA due to reduced
      capacity of NER may result in cellular death, premature aging, mutagenesis and
      carcinogenesis of the skin. So, NER is an important protection against these
      changes. There are three representative genodermatoses resulting from genetic
      defects in NER: xeroderma pigmentosum (XP), Cockayne syndrome (CS), and
      trichothiodystrophy (TTD). In Japan, CS is similarly rare but XP is more common
      and TTD is less common compared to Western countries. In 1998, we established the
      system for the diagnosis of these disorders and we have been performing DNA
      repair and genetic analysis for more than 400 samples since then. At present,
      there is no cure for any human genetic disorder. Early diagnosis and symptomatic
      treatment of neurological, ocular and dermatological abnormalities should
      contribute to prolonging life and elevating QOL in patients. 

PMID- 23966816
TI  - Presentation of a Patient who Underwent Fertility-Sparing Surgeries for
      Contralateral Recurrence of Ovarian Immature Teratoma with Gliomatosis Peritonei.
AB  - We report a patient who has maintained a regular menstrual cycle despite
      undergoing cystectomy and chemotherapy for contralateral recurrence of ovarian
      immature teratoma with gliomatosis peritonei. We initially performed a fertility
      sparing right salpingo-oophorectomy, omentectomy and peritoneal biopsy for
      immature teratoma with gliomatosis peritonei, with adjuvant chemotherapy; we
      performed a left ovarian cystectomy and peritoneal biopsy for mature cystic
      teratoma with gliomatosis peritonei 16 months after the first surgery, a
      fertility-sparing left ovarian cystectomy and peritoneal biopsy for contralateral
      recurrence of ovarian immature teratoma with gliomatosis peritonei 60 months
      after the first surgery, and a left ovarian cystectomy and peritoneal and
      external iliac lymph node biopsy for endometrial cyst with gliomatosis peritonei
      71 months after first surgery. The peritoneal gliomatosis lesions gradually
      decreased through the 4 surgeries over 8 years. The patient has maintained a
      regular menstrual cycle and currently shows no evidence of disease. 

PMID- 23966817
TI  - The Eradication of Helicobacter pylori does not Affect Glycemic Control in
      Japanese Subjects with Type 2 Diabetes.
AB  - Since infection with Helicobacter pylori has been suggested to play a pathogenic
      role in diabetes mellitus, we investigated whether eradication therapy for H.
      pylori might affect glycemic control in Japanese subjects with type 2 diabetes. A
      total of 72 subjects (55 males, 17 females; aged 63.7 years) with type 2 diabetes
      who received eradication therapy for H. pylori were included. The change of their
      blood glycosylated hemoglobin (A1C) levels 3 months before (-3 m) the H. pylori
      eradication, as well as 3 months (3 m) and 6 months (6 m) after were evaluated.
      Their A1C levels did not show any significant change after therapy {6.9 [0.1]% (
      3 m) to 7.0 [0.1]% (3 m); P = 0.3, 7.0 [0.1] (6 m); P = 0.3}. Our findings
      suggest that the eradication therapy for H. pylori does not, at least profoundly,
      affect glycemic control in Japanese subjects with type 2 diabetes. 

PMID- 23966818
TI  - All the Vice Chancellor's Neuroscientists: Unity to Achieve Success in Solving
      Malaysia's Diseases via Upgrading Clinical Services and Neuroscience Research.
AB  - President Obama of the United States of America announced this April the Brain
      Research Through Advancing Innovative Neurotechnologies (BRAIN for short)
      investment, while Professor Henry Markram's team based in the European Union will
      spend over a billion euros on the Human Brain Project, breaking through the
      unknowns in the fifth science of the decade: Neuroscience. Malaysia's growth in
      the same field needs to be augmented, and thus the Universiti Sains Malaysia's
      vision is to excel in the field of clinical brain sciences, mind sciences and
      neurosciences. This will naturally bring up the level of research in the country
      simultaneously. Thus, a center was recently established to coordinate this
      venture. The four-year Integrated Neuroscience Program established recently will
      be a sustainable source of neuroscientists for the country. We hope to establish
      ourselves by 2020 as a global university with neurosciences research as an
      important flagship. 

PMID- 23966819
TI  - Review of the medicinal effects of tualang honey and a comparison with manuka
      honey.
AB  - Tualang honey (TH) is a Malaysian multifloral jungle honey. In recent years,
      there has been a marked increase in the number of studies published in medical
      databases regarding its potential health benefits. The honey is produced by the
      rock bee (Apis dorsata), which builds hives on branches of tall Tualang trees
      located mainly in the north-western region of Peninsular Malaysia. This review
      collates the results of the various studies of TH that range from research on
      tissue culture to randomised control clinical trials. Findings thus far show
      that, TH has antimicrobial, anti-inflammatory, antioxidant, antimutagenic,
      antitumor, and antidiabetic properties, in addition to wound-healing attributes.
      Some of its properties are similar to the well-researched Manuka honey (New
      Zealand and/or Australian monofloral honey). Distinct differences include higher
      phenolics, flavonoids, and 5-(hydroxymethyl) furfural (HMF). Compared with Manuka
      honey, TH is also more effective against some gram-negative bacterial strains in
      burn wounds. 

PMID- 23966820
TI  - Isolation of Extended Spectrum beta-lactamase (ESBL) Producing Bacteria from
      Urban Surface Waters in Malaysia.
AB  - BACKGROUND: This was a preliminary study to test for the presence of multiple
      antibiotic-resistant extended spectrum beta-lactamase (ESBL) producing bacteria
      in Malaysian urban surface waters. Although the literature review revealed
      several published papers on clinical ESBL isolates in Malaysia, none were found
      on ESBL isolates obtained from local surface waters. METHODS: Isolated bacterial
      species were tested for resistance to cefotaxime, amoxicillin/clavulanate and
      aztreonam, and susceptibility to imipenem and meropenem using antibiotic
      susceptibility testing (AST) by disc diffusion. This served as a screening step
      to detect bacteria that could be potential ESBL species. 16S ribose ribonucleic
      acid (rRNA) polymerase chain reaction (PCR) testing with two clusters of bla
      (beta-lactamase) gene primers was used to test for the bla genes CTX-M (Groups 1,
      2, 9), OXA-1, SHV and TEM. RESULTS: A total of 19 isolates were found, possessing
      at least one of the bla genes tested for. There was a relatively high occurrence
      of CTX-M genes (84.2%) among these, followed by TEM genes (47.4%). The isolates
      were identified as Enterobacteriaceae (89.5%), predominantly Escherichia coli and
      Klebsiella pneumoniae. CONCLUSION: There appears to be a high occurrence of ESBL
      bacteria in local surface waters, among these being opportunistic pathogens. The
      persistence and spread of these species in the environment poses a threat to
      exposed human populations.

PMID- 23966821
TI  - Evaluation of mean glandular dose and modulation transfer function for different
      tube potentials and target-filter combinations in computed radiography
      mammography.
AB  - BACKGROUND: Different target-filter combinations in computed radiography have
      different impacts on the dose and image quality in digital radiography. This
      study aims to evaluate the mean glandular dose (MGD) and modulation transfer
      function (MTF) of various target-filter combinations by investigating the signal
      intensities of X-ray beams. METHODS: General Electric (GE) Senographe DMR Plus
      mammography unit was used for MGD and MTF evaluation. The measured MGD was
      compared with the dose reference level (DRL), whereas the MTF was evaluated using
      ImageJ 1.46o software. A modified Mammography Accreditation Phantom RMI 156 was
      exposed using different target-filter combinations of molybdenum-molybdenum (Mo
      Mo), molybdenum-rhodium (Mo-Rh) and rhodium-rhodium (Rh-Rh) at two different tube
      voltages, 26 kV and 32 kV with 50 mAs. RESULTS: In the MGD evaluations, all
      target-filters gave an MGD value of < 1.5 mGy. The one-way ANOVA test showed a
      highly significant interaction between the MGD and the kilovoltage and target
      filter material used (26 kV: F (2,12) = 49,234, P = 0.001;32 kV: F (2,12) =
      89,972, P = 0.001). A Tukey post-hoc test revealed that the MGD for 26 kV and 32
      kV was highly affected by the target-filter combinations. The test of homogeneity
      of variances indicates that the MGD varies significantly for 26 kV and 32 kV
      images (0.045 and 0.030 (P < 0.05), respectively). However, the one-way ANOVA for
      the MTF shows that no significant difference exists between the target-filter
      combinations used with 26 kV and 32 kV images either in parallel or perpendicular
      to the chest wall side F (2,189) = 0.26, P > 0.05). CONCLUSION: Higher tube
      voltage and atomic number target-filter yield higher MGD values. However, the MTF
      is independent of the X-ray energy and the type of target-filter combinations
      used.

PMID- 23966822
TI  - Socio-demographic and Clinical Profile of Substance Abusers Attending a Regional
      Drug De-addiction Centre in Chronic Conflict Area: Kashmir, India.
AB  - BACKGROUND: The menace of substance abuse is not only a socially unacceptable
      reality, but in its entirety is a disease and emerging as a major public health
      challenge. OBJECTIVE: To study the socio-demographic and clinical profile of
      patients attending the drug de-addiction centre. METHODS: A descriptive study was
      undertaken in a drug de-addiction centre at the Police Hospital in Srinagar, and
      all patients (198) who were admitted during this period were interviewed.
      RESULTS: The mean (SD) age of patients was 26.8 years (SD 7.37), and over half
      (56%) belonged to the lower-middle social class. Poly-substance abuse was seen in
      91.9%; medicinal opioids and cannabis were the most common substances abused.
      Most common age of initiation was 11-20 years (76.8%), with peer pressure and
      relief from a negative mood state being the most common reasons given for
      starting the drug(s). Prevalence of a co-morbid psychiatric disorder was high, on
      the order of 49.5%. A high rate of volatile substance use was observed among
      adolescents (54.5%). CONCLUSION: A pattern of poly-substance abuse was found to
      be quite common in patients, and use of volatile substances at a very young age
      emerged as a new trend. The dreadful repercussions of substance abuse justify the
      urgency to evolve a comprehensive strategy.

PMID- 23966823
TI  - Serum Sodium and Potassium Levels in Cerebro-vascular Accident Patients.
AB  - BACKGROUND: We aim to assess serum sodium and potassium levels in patients with
      different types of cerebro-vascular accidents (CVA) in comparison to control
      group. METHODS: A comparative cross-sectional study conducted on patients
      admitted to the emergency department from January to August 2012. Control group
      consisted of patients admitted to emergency department due to common cold,
      urinary tract infection, low back pain, cluster, and tension headache or
      migraine. Serum sodium and potassium levels were measured via standard laboratory
      methods. RESULTS: There were 77 patients in control group and 78 in CVA group.
      Forty nine patients from the CVA group had ischemic CVA, 11 had hemorrhagic CVA
      and 18 suffered a transient ischemic attack (TIA). Serum sodium level in control
      group was significantly lower than in patients with TIA, ischemic CVA, and
      hemorrhagic CVA (P < 0.001). Serum potassium level in control group was higher
      than patients with TIA, ischemic CVA, and hemorrhagic CVA (P < 0.001). Patients
      with hemorrhagic CVA showed significantly lower serum potassium level than
      patients with TIA and ischemic CVA (P < 0.001). Correspondingly, it was observed
      that serum sodium to potassium ratio was higher in patients with TIA, ischemic
      CVA, and hemorrhagic CVA (P < 0.001). In patients with hemorrhagic CVA serum
      sodium to potassium ratio was higher when compared to patients with TIA and
      ischemic CVA (P < 0.001). CONCLUSION: This study shows that higher serum sodium
      and lower serum potassium level may be associated with higher incidence of CVA.
      Further studies are paramount to elucidate the role of serum electrolyte levels
      in vascular events.

PMID- 23966824
TI  - Ten-year Investigation of Clinical, Laboratory and Radiologic Manifestations and
      Complications in Patients with Takayasu's Arteritis in Three University
      Hospitals.
AB  - BACKGROUND: Takayasu arteritis is a condition of unknown aetiology that affects
      the aorta and its primary branches. The disease has been primarily recognized and
      described in Asia. The aims of this study were to identify the main clinical,
      laboratory, and angiographic features of Takayasu arteritis in Iranian patients
      over a 10 year period from 2000 to 2010. METHODS: Data were obtained from
      angiographic and medical records of patients treated at Shahid-Rajai, Taleghani,
      and Loghman Hospitals during the above-mentioned time period. The criteria for
      definitions and findings were those proposed by the American College of
      Rheumatology. RESULTS: A total of 15 patients were identified. The median age at
      presentation was 36 years and 73.3% of patients were females. Fever was the most
      common presentation. According to "modified" National Institute of Health
      criteria, 44.7% of patients were in the acute phase of disease with systemic
      symptoms such as fever, weight loss, and elevated C-reactive protein (CRP)
      levels. Immunological markers such as antinuclear antibodies (ANA) and
      antineutrophil cytoplasmic antibodies (C-ANCA) were absent. The tuberculin test
      result was positive in 40% of the patients. Vascular bruit was present in 86.7%
      and hypertension was detected in 53.3% with 13.3% having associated renal artery
      stenosis. The angiographic manifestations were classified as; type I,
      cervicobrachial type (26.6%); type II, thoracoabdominal type (20.0%); type III,
      peripheral type (6.6%); and type IV, generalised type (46.7%). Coronary arteries
      were involved in three cases, pulmonary in two and renal in two. CONCLUSION:
      Based on our findings, the most common clinical, laboratory and angiographic
      findings were fever, increased erythrocyte sedimentation rate (ESR) and stenosis,
      respectively. Because of dangerous consequences of this disease, attention to
      fever and increased ESR, especially in young women may be helpful for physicians
      to prevent diagnosis delay.

PMID- 23966825
TI  - Survey on maternal satisfaction in receiving spinal anaesthesia for caesarean
      section.
AB  - BACKGROUND: This study was undertaken to evaluate patient satisfaction after
      spinal anaesthesia, which is the most frequently administered anaesthesia in
      obstetric patients. METHODS: A cross-sectional study of patients who underwent
      caesarean section under spinal anaesthesia in the operating rooms of Hospital
      Teluk Intan was conducted. Post-operative survey of patients on the day after
      surgery was conducted by collecting pre-operative and intra-operative data on a
      constructed questionnaire. Post-operative data, including satisfaction and
      understanding the anaesthetist's explanation regarding anaesthesia, satisfaction
      in receiving spinal anaesthesia and adverse effects, and willingness to accept or
      refuse spinal anaesthesia for a similar surgery again, were inquired by trained
      anaesthesia personnel. RESULTS: A total of 200 pregnant patients, with age
      ranging from 17 to 45 years, were surveyed: 64.5% Malay, 17% Indian, 14% Chinese
      and 4.5% others. All (100%) the patients were satisfied with the explanation
      provided regarding the choices of anaesthesia, but 2% could not concentrate on
      the explanation because of labour pain. Overall, the average satisfaction with
      spinal anaesthesia administration was divided into 194 (97%) satisfied patients
      and 6 (3%) dissatisfied patients. Factors associated with dissatisfaction were
      inadequate analgesia during surgery and failed spinal anaesthesia. Post-operative
      complications included spinal headache 5 (2.5%), post-operative nausea and
      vomiting (PONV) 1 (0.5%), pain at the surgical site 2 (1%) and backache 2 (1%).
      Furthermore, 177 (88.5%) patients would opt for spinal anaesthesia in future for
      similar surgery, if required; 16 (8%) would not; and 7 (3.5%) were not sure. The
      reasons for refusal to receive spinal anaesthesia were as follows: awareness and
      failed regional anaesthesia. CONCLUSION: The patients receiving spinal
      anaesthesia demonstrated a high rate of patient satisfaction. Ensuring the
      quality of spinal anaesthesia, improving clinical skill of the
      anaesthesiologists, and prevention of side effects might improve patient
      satisfaction.

PMID- 23966826
TI  - The Outcomes of Pars Plana Vitrectomy without Tamponade for Tractional Retinal
      Detachment Secondary to Diabetic Retinopathy.
AB  - BACKGROUND: The objective of this research was to evaluate the outcomes of pars
      plana vitrectomy (PPV) without the use of an ocular tamponade in patients with
      tractional retinal detachment (TRD) secondary to proliferative diabetic
      retinopathy (PDR) presenting to Bahawal Victoria Hospital, Bahawalpur, Pakistan.
      METHODS: This was an interventional study conducted at the Department of
      Ophthalmology, Bahawal Victoria (B.V.) Hospital, Bahawalpur, Pakistan, from July
      2011 to July 2012. A total of 75 patients (84 eyes) with TRD secondary to PDR
      were treated by PPV without using an ocular tamponade. All patients included in
      the study had a TRD secondary to PDR but did not have or develop retinal breaks
      before or during the study period. The surgical procedure included a PPV combined
      with the removal of the tractional retinal membranes and the application of
      endolaser photocoagulation to the retina. The mean follow-up period was 12
      months. RESULTS: The study included 75 patients (84 eyes). Among these, 40
      patients were females and 35 males. Successful retinal reattachment was observed
      in 78 of the operated eyes (92.8%). In these patients, the retina remained
      attached until the end of the 12 month follow-up period. Improvement in best
      corrected visual acuity (BCVA) was seen in 63 eyes (75%). The visual acuity
      remained unchanged in nine eyes (10.7%). Mean improvement in BCVA was 2.00 +/-
      1.24 at baseline to 1.24 +/- 1.22 (P = 0.010) at the end of the follow-up period.
      CONCLUSION: In the absence of retinal breaks, a TRD secondary to PDR can be
      successfully treated and improved by PPV without the use of an ocular tamponade.

PMID- 23966827
TI  - Immune mechanism: a 'double-edged sword'.
AB  - Immunology has now developed into an independent discipline in medicine which
      covers not only germ infection which is related to immunity solely but also
      covers a lot of non-infectious diseases such as autoimmune disease, allergies,
      and others. Therefore, "The Immune Mechanism: "A Double-Edged Sword" means that
      the immune mechanism (consisted of antibody mediated mechanism and T cell
      mediated mechanism), just like one edge playing the role of giving benefit
      (immunity) as it destroys the agent of infection, and another one can be
      detrimental as it will cause tissue/cell damages and then give rise to immune
      diseases (immunopathology). Now, the prevalence of these immune diseases is on
      the rise and has become a new challenge to our country towards developed country
      in 2020. Therefore, we have to make ample preparation (laboratory
      facilities/services, main power, and research) from now on in order to face the
      problems and challenges. 

PMID- 23966828
TI  - Spontaneous Resolution of Emphysematous Gastritis with Vaso-occlusive Disease-A
      Case Report.
AB  - Emphysematous gastritis secondary to vaso-occlusive disease is a surgical
      emergency. It is a rare yet severe form of widespread phlegmonous gastritis. It
      is caused by corrosive ingestion, alcohol abuse, and on rare occasions,
      infections. The clinical presentation is diagnostic with supportive information
      from contrast-enhanced computed tomography (CECT) of the abdomen and
      gastroduodenoscopy. Here, we describe a case of emphysematous gastritis with
      spontaneous vaso-occlusive disease that was successfully managed without surgery.

PMID- 23966829
TI  - Mesenchymal chondrosarcoma: a case report.
AB  - Mesenchymal chondrosarcoma is a rare disease with poor prognosis. Treatment
      including wide or radical excision is very important. Radiotherapy and
      chemotherapy are additional treatment options, but no conclusive results for
      their efficacy have been shown until date. Imaging modalities can give important
      clues for diagnosis and management planning. Angioembolization before surgery
      could be useful as prophylaxis to control intraoperative bleeding, increasing the
      likelihood of complete resection. 

PMID- 23966830
TI  - Misdiagnosed case of bronchial carcinoid presenting with refractory dyspnoea and
      wheeze: a rare case report and review of literature.
AB  - A 59-year-old male smoker presented with persistent wheezing and occasional
      coughing that had been ongoing for two years and had been unsuccessfully treated
      with an inhalational beta2 agonist, an anticholinergic and an inhalational
      steroid in the last year. On clinical examination, a left-sided wheeze was
      detected. The initial chest X-ray was normal. A computed tomography (CT) scan of
      thorax demonstrated a mass lesion in the left main bronchus. On subsequent
      bronchoscopy, an endobronchial polypoid mass was detected in the left main
      bronchus, completely occluding the bronchial lumen. A biopsy taken from the mass
      revealed features of bronchial carcinoid. Bronchial carcinoid can present
      uncommonly with wheezes, resulting in misdiagnosis as bronchial asthma or chronic
      obstructive pulmonary disease (COPD). If an asthma or COPD patient does not
      respond to conventional therapy, a CT scan and subsequent bronchoscopy is
      warranted. 

PMID- 23966831
TI  - Lymphocytic mastitis mimicking breast carcinoma, radiology and pathology
      correlation: review of two cases.
AB  - Lymphocytic mastitis, or diabetic mastopathy, is an unusual finding in early
      onset and long-standing diabetes. It can presents as a non-tender or tender
      palpable breast mass. Mammogram and ultrasound frequently demonstrate findings
      suspicious of malignancy, thus biopsy and histological confirmation is usually
      required. We reviewed two cases of lymphocytic mastitis with characteristics
      findings on mammogram, ultrasound, and histopathology. Diagnoses were confirmed
      with excision biopsy. 

PMID- 23966832
TI  - A Bacteriophage tailspike domain promotes self-cleavage of a human membrane-bound
      transcription factor, the myelin regulatory factor MYRF.
AB  - Myelination of the central nervous system (CNS) is critical to vertebrate nervous
      systems for efficient neural signaling. CNS myelination occurs as
      oligodendrocytes terminally differentiate, a process regulated in part by the
      myelin regulatory factor, MYRF. Using bioinformatics and extensive biochemical
      and functional assays, we find that MYRF is generated as an integral membrane
      protein that must be processed to release its transcription factor domain from
      the membrane. In contrast to most membrane-bound transcription factors, MYRF
      proteolysis seems constitutive and independent of cell- and tissue-type, as we
      demonstrate by reconstitution in E. coli and yeast. The apparent absence of
      physiological cues raises the question as to how and why MYRF is processed. By
      using computational methods capable of recognizing extremely divergent sequence
      homology, we identified a MYRF protein domain distantly related to bacteriophage
      tailspike proteins. Although occurring in otherwise unrelated proteins, the phage
      domains are known to chaperone the tailspike proteins' trimerization and auto
      cleavage, raising the hypothesis that the MYRF domain might contribute to a novel
      activation method for a membrane-bound transcription factor. We find that the
      MYRF domain indeed serves as an intramolecular chaperone that facilitates MYRF
      trimerization and proteolysis. Functional assays confirm that the chaperone
      domain-mediated auto-proteolysis is essential both for MYRF's transcriptional
      activity and its ability to promote oligodendrocyte maturation. This work thus
      reveals a previously unknown key step in CNS myelination. These data also
      reconcile conflicting observations of this protein family, different members of
      which have been identified as transmembrane or nuclear proteins. Finally, our
      data illustrate a remarkable evolutionary repurposing between bacteriophages and
      eukaryotes, with a chaperone domain capable of catalyzing trimerization-dependent
      auto-proteolysis in two entirely distinct protein and cellular contexts, in one
      case participating in bacteriophage tailspike maturation and in the other
      activating a key transcription factor for CNS myelination. 

PMID- 23966834
TI  - Myelination borrows a trick from phage.

PMID- 23966833
TI  - MYRF is a membrane-associated transcription factor that autoproteolytically
      cleaves to directly activate myelin genes.
AB  - The myelination of axons is a crucial step during vertebrate central nervous
      system (CNS) development, allowing for rapid and energy efficient saltatory
      conduction of nerve impulses. Accordingly, the differentiation of
      oligodendrocytes, the myelinating cells of the CNS, and their expression of
      myelin genes are under tight transcriptional control. We previously identified a
      putative transcription factor, Myelin Regulatory Factor (Myrf), as being vital
      for CNS myelination. Myrf is required for the generation of CNS myelination
      during development and also for its maintenance in the adult. It has been
      controversial, however, whether Myrf directly regulates transcription, with
      reports of a transmembrane domain and lack of nuclear localization. Here we show
      that Myrf is a membrane-associated transcription factor that undergoes an
      activating proteolytic cleavage to separate its transmembrane domain-containing C
      terminal region from a nuclear-targeted N-terminal region. Unexpectedly, this
      cleavage event occurs via a protein domain related to the autoproteolytic
      intramolecular chaperone domain of the bacteriophage tail spike proteins, the
      first time this domain has been found to play a role in eukaryotic proteins.
      Using ChIP-Seq we show that the N-terminal cleavage product directly binds the
      enhancer regions of oligodendrocyte-specific and myelin genes. This binding
      occurs via a defined DNA-binding consensus sequence and strongly promotes the
      expression of target genes. These findings identify Myrf as a novel example of a
      membrane-associated transcription factor and provide a direct molecular mechanism
      for its regulation of oligodendrocyte differentiation and CNS myelination. 

PMID- 23966836
TI  - New insights into unusual genetic disorder pave the way for promising treatments.

PMID- 23966835
TI  - Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated
      in adults by compensatory recruitment of mGluR5 and Erk signaling.
AB  - Tuberous sclerosis complex (TSC) is a multisystem genetic disease that manifests
      with mental retardation, tumor formation, autism, and epilepsy. Heightened
      signaling through the mammalian target of rapamycin (mTOR) pathway is involved in
      TSC pathology, however it remains unclear how other signaling pathways are
      perturbed and contribute to disease symptoms. Reduced long-term depression (LTD)
      was recently reported in TSC mutant mice. We find that although reduced LTD is a
      feature of the juvenile mutant hippocampus, heightened expression of metabotropic
      glutamate receptor 5 and constitutively activated Erk signaling in the adult
      hippocampus drives wild-type levels of LTD. Increased mGluR5 and Erk results in a
      novel mTOR-independent LTD in CA1 hippocampus of adult mice, and contributes to
      the development of epileptiform bursting activity in the TSC2(+/-) CA3 region of
      the hippocampus. Inhibition of mGluR5 or Erk signaling restores appropriate mTOR
      dependence to LTD, and significantly reduces epileptiform bursting in TSC2(+/-)
      hippocampal slices. We also report that adult TSC2(+/-) mice exhibit a subtle
      perseverative behavioral phenotype that is eliminated by mGluR5 antagonism. These
      findings highlight the potential of modulating the mGluR5-Erk pathway in a
      developmental stage-specific manner to treat TSC. 

PMID- 23966837
TI  - Developmental changes in the in vitro activated regenerative activity of
      primitive mammary epithelial cells.
AB  - Many normal adult tissues contain rare stem cells with extensive self-maintaining
      regenerative potential. During development, the stem cells of the hematopoietic
      and neural systems undergo intrinsically specified changes in their self-renewal
      potential. In the mouse, mammary stem cells with transplantable regenerative
      activity are first detectable a few days before birth. They share some phenotypic
      properties with their adult counterparts but are enriched in a subpopulation that
      displays a distinct gene expression profile. Here we show that fetal mammary
      epithelial cells have a greater direct and inducible growth potential than their
      adult counterparts. The latter feature is revealed in a novel culture system that
      enables large numbers of in vitro clonogenic progenitors as well as mammary stem
      cells with serially transplantable activity to be produced within 7 days from
      single fetal or adult input cells. We further show that these responses are
      highly dependent on novel factors produced by fibroblasts. These findings provide
      new avenues for elucidating mechanisms that regulate normal mammary epithelial
      stem cell properties at the single-cell level, how these change during
      development, and how their perturbation may contribute to transformation. 

PMID- 23966839
TI  - Inclusion of ethical issues in dementia guidelines: a thematic text analysis.
AB  - BACKGROUND: Clinical practice guidelines (CPGs) aim to improve professionalism in
      health care. However, current CPG development manuals fail to address how to
      include ethical issues in a systematic and transparent manner. The objective of
      this study was to assess the representation of ethical issues in general CPGs on
      dementia care. METHODS AND FINDINGS: To identify national CPGs on dementia care,
      five databases of guidelines were searched and national psychiatric associations
      were contacted in August 2011 and in June 2013. A framework for the assessment of
      the identified CPGs' ethical content was developed on the basis of a prior
      systematic review of ethical issues in dementia care. Thematic text analysis and
      a 4-point rating score were employed to assess how ethical issues were addressed
      in the identified CPGs. Twelve national CPGs were included. Thirty-one ethical
      issues in dementia care were identified by the prior systematic review. The
      proportion of these 31 ethical issues that were explicitly addressed by each CPG
      ranged from 22% to 77%, with a median of 49.5%. National guidelines differed
      substantially with respect to (a) which ethical issues were represented, (b)
      whether ethical recommendations were included, (c) whether justifications or
      citations were provided to support recommendations, and (d) to what extent the
      ethical issues were explained. CONCLUSIONS: Ethical issues were inconsistently
      addressed in national dementia guidelines, with some guidelines including most
      and some including few ethical issues. Guidelines should address ethical issues
      and how to deal with them to help the medical profession understand how to
      approach care of patients with dementia, and for patients, their relatives, and
      the general public, all of whom might seek information and advice in national
      guidelines. There is a need for further research to specify how detailed ethical
      issues and their respective recommendations can and should be addressed in
      dementia guidelines. Please see later in the article for the Editors' Summary.

PMID- 23966840
TI  - Reproductive and maternal health in the post-2015 era: cervical cancer must be a
      priority.

PMID- 23966838
TI  - Towards universal voluntary HIV testing and counselling: a systematic review and
      meta-analysis of community-based approaches.
AB  - BACKGROUND: Effective national and global HIV responses require a significant
      expansion of HIV testing and counselling (HTC) to expand access to prevention and
      care. Facility-based HTC, while essential, is unlikely to meet national and
      global targets on its own. This article systematically reviews the evidence for
      community-based HTC. METHODS AND FINDINGS: PubMed was searched on 4 March 2013,
      clinical trial registries were searched on 3 September 2012, and Embase and the
      World Health Organization Global Index Medicus were searched on 10 April 2012 for
      studies including community-based HTC (i.e., HTC outside of health facilities).
      Randomised controlled trials, and observational studies were eligible if they
      included a community-based testing approach and reported one or more of the
      following outcomes: uptake, proportion receiving their first HIV test, CD4 value
      at diagnosis, linkage to care, HIV positivity rate, HTC coverage, HIV incidence,
      or cost per person tested (outcomes are defined fully in the text). The following
      community-based HTC approaches were reviewed: (1) door-to-door testing
      (systematically offering HTC to homes in a catchment area), (2) mobile testing
      for the general population (offering HTC via a mobile HTC service), (3) index
      testing (offering HTC to household members of people with HIV and persons who may
      have been exposed to HIV), (4) mobile testing for men who have sex with men, (5)
      mobile testing for people who inject drugs, (6) mobile testing for female sex
      workers, (7) mobile testing for adolescents, (8) self-testing, (9) workplace HTC,
      (10) church-based HTC, and (11) school-based HTC. The Newcastle-Ottawa Quality
      Assessment Scale and the Cochrane Collaboration's "risk of bias" tool were used
      to assess the risk of bias in studies with a comparator arm included in pooled
      estimates. 117 studies, including 864,651 participants completing HTC, met the
      inclusion criteria. The percentage of people offered community-based HTC who
      accepted HTC was as follows: index testing, 88% of 12,052 participants; self
      testing, 87% of 1,839 participants; mobile testing, 87% of 79,475 participants;
      door-to-door testing, 80% of 555,267 participants; workplace testing, 67% of
      62,406 participants; and school-based testing, 62% of 2,593 participants. Mobile
      HTC uptake among key populations (men who have sex with men, people who inject
      drugs, female sex workers, and adolescents) ranged from 9% to 100% (among 41,110
      participants across studies), with heterogeneity related to how testing was
      offered. Community-based approaches increased HTC uptake (relative risk [RR]
      10.65, 95% confidence interval [CI] 6.27-18.08), the proportion of first-time
      testers (RR 1.23, 95% CI 1.06-1.42), and the proportion of participants with CD4
      counts above 350 cells/ul (RR 1.42, 95% CI 1.16-1.74), and obtained a lower
      positivity rate (RR 0.59, 95% CI 0.37-0.96), relative to facility-based
      approaches. 80% (95% CI 75%-85%) of 5,832 community-based HTC participants
      obtained a CD4 measurement following HIV diagnosis, and 73% (95% CI 61%-85%) of
      527 community-based HTC participants initiated antiretroviral therapy following a
      CD4 measurement indicating eligibility. The data on linking participants without
      HIV to prevention services were limited. In low- and middle-income countries, the
      cost per person tested ranged from US$2-US$126. At the population level,
      community-based HTC increased HTC coverage (RR 7.07, 95% CI 3.52-14.22) and
      reduced HIV incidence (RR 0.86, 95% CI 0.73-1.02), although the incidence
      reduction lacked statistical significance. No studies reported any harm arising
      as a result of having been tested. CONCLUSIONS: Community-based HTC achieved high
      rates of HTC uptake, reached people with high CD4 counts, and linked people to
      care. It also obtained a lower HIV positivity rate relative to facility-based
      approaches. Further research is needed to further improve acceptability of
      community-based HTC for key populations. HIV programmes should offer community
      based HTC linked to prevention and care, in addition to facility-based HTC, to
      support increased access to HIV prevention, care, and treatment. REVIEW
      REGISTRATION: International Prospective Register of Systematic Reviews
      CRD42012002554 Please see later in the article for the Editors' Summary.

PMID- 23966841
TI  - Expanding disease definitions in guidelines and expert panel ties to industry: a
      cross-sectional study of common conditions in the United States.
AB  - BACKGROUND: Financial ties between health professionals and industry may unduly
      influence professional judgments and some researchers have suggested that
      widening disease definitions may be one driver of over-diagnosis, bringing
      potentially unnecessary labeling and harm. We aimed to identify guidelines in
      which disease definitions were changed, to assess whether any proposed changes
      would increase the numbers of individuals considered to have the disease, whether
      potential harms of expanding disease definitions were investigated, and the
      extent of members' industry ties. METHODS AND FINDINGS: We undertook a cross
      sectional study of the most recent publication between 2000 and 2013 from
      national and international guideline panels making decisions about definitions or
      diagnostic criteria for common conditions in the United States. We assessed
      whether proposed changes widened or narrowed disease definitions, rationales
      offered, mention of potential harms of those changes, and the nature and extent
      of disclosed ties between members and pharmaceutical or device companies. Of 16
      publications on 14 common conditions, ten proposed changes widening and one
      narrowing definitions. For five, impact was unclear. Widening fell into three
      categories: creating "pre-disease"; lowering diagnostic thresholds; and proposing
      earlier or different diagnostic methods. Rationales included standardising
      diagnostic criteria and new evidence about risks for people previously considered
      to not have the disease. No publication included rigorous assessment of potential
      harms of proposed changes. Among 14 panels with disclosures, the average
      proportion of members with industry ties was 75%. Twelve were chaired by people
      with ties. For members with ties, the median number of companies to which they
      had ties was seven. Companies with ties to the highest proportions of members
      were active in the relevant therapeutic area. Limitations arise from reliance on
      only disclosed ties, and exclusion of conditions too broad to enable analysis of
      single panel publications. CONCLUSIONS: For the common conditions studied, a
      majority of panels proposed changes to disease definitions that increased the
      number of individuals considered to have the disease, none reported rigorous
      assessment of potential harms of that widening, and most had a majority of
      members disclosing financial ties to pharmaceutical companies. Please see later
      in the article for the Editors' Summary.

PMID- 23966843
TI  - Host mobility drives pathogen competition in spatially structured populations.
AB  - Interactions among multiple infectious agents are increasingly recognized as a
      fundamental issue in the understanding of key questions in public health
      regarding pathogen emergence, maintenance, and evolution. The full description of
      host-multipathogen systems is, however, challenged by the multiplicity of factors
      affecting the interaction dynamics and the resulting competition that may occur
      at different scales, from the within-host scale to the spatial structure and
      mobility of the host population. Here we study the dynamics of two competing
      pathogens in a structured host population and assess the impact of the mobility
      pattern of hosts on the pathogen competition. We model the spatial structure of
      the host population in terms of a metapopulation network and focus on two strains
      imported locally in the system and having the same transmission potential but
      different infectious periods. We find different scenarios leading to competitive
      success of either one of the strain or to the codominance of both strains in the
      system. The dominance of the strain characterized by the shorter or longer
      infectious period depends exclusively on the structure of the population and on
      the the mobility of hosts across patches. The proposed modeling framework allows
      the integration of other relevant epidemiological, environmental and demographic
      factors, opening the path to further mathematical and computational studies of
      the dynamics of multipathogen systems. 

PMID- 23966842
TI  - Viral proteins originated de novo by overprinting can be identified by codon
      usage: application to the "gene nursery" of Deltaretroviruses.
AB  - A well-known mechanism through which new protein-coding genes originate is by
      modification of pre-existing genes, e.g. by duplication or horizontal transfer.
      In contrast, many viruses generate protein-coding genes de novo, via the
      overprinting of a new reading frame onto an existing ("ancestral") frame. This
      mechanism is thought to play an important role in viral pathogenicity, but has
      been poorly explored, perhaps because identifying the de novo frames is very
      challenging. Therefore, a new approach to detect them was needed. We assembled a
      reference set of overlapping genes for which we could reliably determine the
      ancestral frames, and found that their codon usage was significantly closer to
      that of the rest of the viral genome than the codon usage of de novo frames.
      Based on this observation, we designed a method that allowed the identification
      of de novo frames based on their codon usage with a very good specificity, but
      intermediate sensitivity. Using our method, we predicted that the Rex gene of
      deltaretroviruses has originated de novo by overprinting the Tax gene.
      Intriguingly, several genes in the same genomic region have also originated de
      novo and encode proteins that regulate the functions of Tax. Such "gene
      nurseries" may be common in viral genomes. Finally, our results confirm that the
      genomic GC content is not the only determinant of codon usage in viruses and
      suggest that a constraint linked to translation must influence codon usage. 

PMID- 23966844
TI  - Characteristic effects of stochastic oscillatory forcing on neural firing:
      analytical theory and comparison to paddlefish electroreceptor data.
AB  - Stochastic signals with pronounced oscillatory components are frequently
      encountered in neural systems. Input currents to a neuron in the form of
      stochastic oscillations could be of exogenous origin, e.g. sensory input or
      synaptic input from a network rhythm. They shape spike firing statistics in a
      characteristic way, which we explore theoretically in this report. We consider a
      perfect integrate-and-fire neuron that is stimulated by a constant base current
      (to drive regular spontaneous firing), along with Gaussian narrow-band noise (a
      simple example of stochastic oscillations), and a broadband noise. We derive
      expressions for the nth-order interval distribution, its variance, and the serial
      correlation coefficients of the interspike intervals (ISIs) and confirm these
      analytical results by computer simulations. The theory is then applied to
      experimental data from electroreceptors of paddlefish, which have two distinct
      types of internal noisy oscillators, one forcing the other. The theory provides
      an analytical description of their afferent spiking statistics during spontaneous
      firing, and replicates a pronounced dependence of ISI serial correlation
      coefficients on the relative frequency of the driving oscillations, and
      furthermore allows extraction of certain parameters of the intrinsic oscillators
      embedded in these electroreceptors. 

PMID- 23966845
TI  - Simulating cortical development as a self constructing process: a novel multi
      scale approach combining molecular and physical aspects.
AB  - Current models of embryological development focus on intracellular processes such
      as gene expression and protein networks, rather than on the complex relationship
      between subcellular processes and the collective cellular organization these
      processes support. We have explored this collective behavior in the context of
      neocortical development, by modeling the expansion of a small number of
      progenitor cells into a laminated cortex with layer and cell type specific
      projections. The developmental process is steered by a formal language analogous
      to genomic instructions, and takes place in a physically realistic three
      dimensional environment. A common genome inserted into individual cells control
      their individual behaviors, and thereby gives rise to collective developmental
      sequences in a biologically plausible manner. The simulation begins with a single
      progenitor cell containing the artificial genome. This progenitor then gives rise
      through a lineage of offspring to distinct populations of neuronal precursors
      that migrate to form the cortical laminae. The precursors differentiate by
      extending dendrites and axons, which reproduce the experimentally determined
      branching patterns of a number of different neuronal cell types observed in the
      cat visual cortex. This result is the first comprehensive demonstration of the
      principles of self-construction whereby the cortical architecture develops. In
      addition, our model makes several testable predictions concerning cell migration
      and branching mechanisms. 

PMID- 23966846
TI  - Priors engaged in long-latency responses to mechanical perturbations suggest a
      rapid update in state estimation.
AB  - In every motor task, our brain must handle external forces acting on the body.
      For example, riding a bike on cobblestones or skating on irregular surface
      requires us to appropriately respond to external perturbations. In these
      situations, motor predictions cannot help anticipate the motion of the body
      induced by external factors, and direct use of delayed sensory feedback will tend
      to generate instability. Here, we show that to solve this problem the motor
      system uses a rapid sensory prediction to correct the estimated state of the
      limb. We used a postural task with mechanical perturbations to address whether
      sensory predictions were engaged in upper-limb corrective movements. Subjects
      altered their initial motor response in ~60 ms, depending on the expected
      perturbation profile, suggesting the use of an internal model, or prior, in this
      corrective process. Further, we found trial-to-trial changes in corrective
      responses indicating a rapid update of these perturbation priors. We used a
      computational model based on Kalman filtering to show that the response
      modulation was compatible with a rapid correction of the estimated state engaged
      in the feedback response. Such a process may allow us to handle external
      disturbances encountered in virtually every physical activity, which is likely an
      important feature of skilled motor behaviour. 

PMID- 23966847
TI  - Sensory information and encounter rates of interacting species.
AB  - Most motile organisms use sensory cues when searching for resources, mates, or
      prey. The searcher measures sensory data and adjusts its search behavior based on
      those data. Yet, classical models of species encounter rates assume that
      searchers move independently of their targets. This assumption leads to the
      familiar mass action-like encounter rate kinetics typically used in modeling
      species interactions. Here we show that this common approach can mischaracterize
      encounter rate kinetics if searchers use sensory information to search actively
      for targets. We use the example of predator-prey interactions to illustrate that
      predators capable of long-distance directional sensing can encounter prey at a
      rate proportional to prey density to the [Formula: see text] power (where
      [Formula: see text] is the dimension of the environment) when prey density is
      low. Similar anomalous encounter rate functions emerge even when predators pursue
      prey using only noisy, directionless signals. Thus, in both the high-information
      extreme of long-distance directional sensing, and the low-information extreme of
      noisy non-directional sensing, encounter rate kinetics differ qualitatively from
      those derived by classic theory of species interactions. Using a standard model
      of predator-prey population dynamics, we show that the new encounter rate
      kinetics derived here can change the outcome of species interactions. Our results
      demonstrate how the use of sensory information can alter the rates and outcomes
      of physical interactions in biological systems. 

PMID- 23966848
TI  - Endogenous cholinergic inputs and local circuit mechanisms govern the phasic
      mesolimbic dopamine response to nicotine.
AB  - Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine
      receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental
      area (VTA). Recent data have led to a debate about the principal pathway of
      nicotine action: direct stimulation of the DAergic cells through nAChR
      activation, or disinhibition mediated through desensitization of nAChRs on
      GABAergic interneurons. We use a computational model of the VTA circuitry and
      nAChR function to shed light on this issue. Our model illustrates that the
      alpha4beta2-containing nAChRs either on DA or GABA cells can mediate the acute
      effects of nicotine. We account for in vitro as well as in vivo data, and predict
      the conditions necessary for either direct stimulation or disinhibition to be at
      the origin of DA activity increases. We propose key experiments to disentangle
      the contribution of both mechanisms. We show that the rate of endogenous
      acetylcholine input crucially determines the evoked DA response for both
      mechanisms. Together our results delineate the mechanisms by which the VTA
      mediates the acute rewarding properties of nicotine and suggest an acetylcholine
      dependence hypothesis for nicotine reinforcement. 

PMID- 23966849
TI  - Biochemical competition makes fatty-acid beta-oxidation vulnerable to substrate
      overload.
AB  - Fatty-acid metabolism plays a key role in acquired and inborn metabolic diseases.
      To obtain insight into the network dynamics of fatty-acid beta-oxidation, we
      constructed a detailed computational model of the pathway and subjected it to a
      fat overload condition. The model contains reversible and saturable enzyme
      kinetic equations and experimentally determined parameters for rat-liver enzymes.
      It was validated by adding palmitoyl CoA or palmitoyl carnitine to isolated rat
      liver mitochondria: without refitting of measured parameters, the model correctly
      predicted the beta-oxidation flux as well as the time profiles of most acyl
      carnitine concentrations. Subsequently, we simulated the condition of obesity by
      increasing the palmitoyl-CoA concentration. At a high concentration of palmitoyl
      CoA the beta-oxidation became overloaded: the flux dropped and metabolites
      accumulated. This behavior originated from the competition between acyl CoAs of
      different chain lengths for a set of acyl-CoA dehydrogenases with overlapping
      substrate specificity. This effectively induced competitive feedforward
      inhibition and thereby led to accumulation of CoA-ester intermediates and
      depletion of free CoA (CoASH). The mitochondrial [NAD+]/[NADH] ratio modulated
      the sensitivity to substrate overload, revealing a tight interplay between
      regulation of beta-oxidation and mitochondrial respiration.

PMID- 23966850
TI  - Spike triggered hormone secretion in vasopressin cells; a model investigation of
      mechanism and heterogeneous population function.
AB  - Vasopressin neurons generate distinctive phasic patterned spike activity in
      response to elevated extracellular osmotic pressure. These spikes are generated
      in the cell body and are conducted down the axon to the axonal terminals where
      they trigger Ca2+ entry and subsequent exocytosis of hormone-containing vesicles
      and secretion of vasopressin. This mechanism is highly non-linear, subject to
      both frequency facilitation and fatigue, such that the rate of secretion depends
      on both the rate and patterning of the spike activity. Here we used computational
      modelling to investigate this relationship and how it shapes the overall response
      of the neuronal population. We generated a concise single compartment model of
      the secretion mechanism, fitted to experimentally observed profiles of
      facilitation and fatigue, and based on representations of the hypothesised
      underlying mechanisms. These mechanisms include spike broadening, Ca2+ channel
      inactivation, a Ca2+ sensitive K+ current, and releasable and reserve pools of
      vesicles. We coupled the secretion model to an existing integrate-and-fire based
      spiking model in order to study the secretion response to increasing synaptic
      input, and compared phasic and non-phasic spiking models to assess the functional
      value of the phasic spiking pattern. The secretory response of individual phasic
      cells is very non-linear, but the response of a heterogeneous population of
      phasic cells shows a much more linear response to increasing input, matching the
      linear response we observe experimentally, though in this respect, phasic cells
      have no apparent advantage over non-phasic cells. Another challenge for the cells
      is maintaining this linear response during chronic stimulation, and we show that
      the activity-dependent fatigue mechanism has a potentially useful function in
      helping to maintain secretion despite depletion of stores. Without this
      mechanism, secretion in response to a steady stimulus declines as the stored
      content declines.

PMID- 23966851
TI  - Relevance of trehalose in pathogenicity: some general rules, yet many exceptions.

PMID- 23966852
TI  - Bed bugs and infectious disease: a case for the arboviruses.

PMID- 23966853
TI  - Secretion of protective antigens by tissue-stage nematode larvae revealed by
      proteomic analysis and vaccination-induced sterile immunity.
AB  - Gastrointestinal nematode parasites infect over 1 billion humans, with little
      evidence for generation of sterilising immunity. These helminths are highly
      adapted to their mammalian host, following a developmental program through
      successive niches, while effectively down-modulating host immune responsiveness.
      Larvae of Heligmosomoides polygyrus, for example, encyst in the intestinal
      submucosa, before emerging as adult worms into the duodenal lumen. Adults release
      immunomodulatory excretory-secretory (ES) products, but mice immunised with adult
      H. polygyrus ES become fully immune to challenge infection. ES products of the
      intestinal wall 4th stage (L4) larvae are similarly important in host-parasite
      interactions, as they readily generate sterile immunity against infection, while
      released material from the egg stage is ineffective. Proteomic analyses of L4 ES
      identifies protective antigen targets as well as potential tissue-phase
      immunomodulatory molecules, using as comparators the adult ES proteome and a
      profile of H. polygyrus egg-released material. While 135 proteins are shared
      between L4 and adult ES, 72 are L4 ES-specific; L4-specific proteins correspond
      to those whose transcription is restricted to larval stages, while shared
      proteins are generally transcribed by all life cycle forms. Two protein families
      are more heavily represented in the L4 secretome, the Sushi domain, associated
      with complement regulation, and the ShK/SXC domain related to a toxin interfering
      with T cell signalling. Both adult and L4 ES contain extensive but distinct
      arrays of Venom allergen/Ancylostoma secreted protein-Like (VAL) members, with
      acetylcholinesterases (ACEs) and apyrase APY-3 particularly abundant in L4 ES.
      Serum antibodies from mice vaccinated with L4 and adult ES react strongly to the
      VAL-1 protein and to ACE-1, indicating that these two antigens represent major
      vaccine targets for this intestinal nematode. We have thus defined an extensive
      and novel repertoire of H. polygyrus proteins closely implicated in immune
      modulation and protective immunity.

PMID- 23966854
TI  - Phosphoantigen/IL2 expansion and differentiation of Vgamma2Vdelta2 T cells
      increase resistance to tuberculosis in nonhuman primates.
AB  - Dominant Vgamma2Vdelta2 T-cell subset exist only in primates, and recognize
      phosphoantigen from selected pathogens including M. tuberculosis(Mtb). In vivo
      function of Vgamma2Vdelta2 T cells in tuberculosis remains unknown. We conducted
      mechanistic studies to determine whether earlier expansion/differentiation of
      Vgamma2Vdelta2 T cells during Mtb infection could increase immune resistance to
      tuberculosis in macaques. Phosphoantigen/IL-2 administration specifically induced
      major expansion and pulmonary trafficking/accumulation of phosphoantigen-specific
      Vgamma2Vdelta2 T cells, significantly reduced Mtb burdens and attenuated
      tuberculosis lesions in lung tissues compared to saline/BSA or IL-2 controls.
      Expanded Vgamma2Vdelta2 T cells differentiated into multifunctional effector
      subpopulations capable of producing anti-TB cytokines IFNgamma, perforin and
      granulysin, and co-producing perforin/granulysin in lung tissue. Mechanistically,
      perforin/granulysin-producing Vgamma2Vdelta2 T cells limited intracellular Mtb
      growth, and macaque granulysin had Mtb-bactericidal effect, and inhibited
      intracellular Mtb in presence of perforin. Furthermore, phosphoantigen/IL2
      expanded Vgamma2Vdelta2 T effector cells produced IL-12, and their
      expansion/differentiation led to enhanced pulmonary responses of peptide-specific
      CD4+/CD8+ Th1-like cells. These results provide first in vivo evidence
      implicating that early expansion/differentiation of Vgamma2Vdelta2 T effector
      cells during Mtb infection increases resistance to tuberculosis. Thus, data
      support a rationale for conducting further studies of the gammadelta T-cell
      targeted treatment of established TB, which might ultimately help explore single
      or adjunctive phosphoantigen expansion of Vgamma2Vdelta2 T-cell subset as
      intervention of MDR-tuberculosis or HIV-related tuberculosis.

PMID- 23966855
TI  - A comprehensive functional portrait of two heat shock factor-type transcriptional
      regulators involved in Candida albicans morphogenesis and virulence.
AB  - Sfl1p and Sfl2p are two homologous heat shock factor-type transcriptional
      regulators that antagonistically control morphogenesis in Candida albicans, while
      being required for full pathogenesis and virulence. To understand how Sfl1p and
      Sfl2p exert their function, we combined genome-wide location and expression
      analyses to reveal their transcriptional targets in vivo together with the
      associated changes of the C. albicans transcriptome. We show that Sfl1p and Sfl2p
      bind to the promoter of at least 113 common targets through divergent binding
      motifs and modulate directly the expression of key transcriptional regulators of
      C. albicans morphogenesis and/or virulence. Surprisingly, we found that Sfl2p
      additionally binds to the promoter of 75 specific targets, including a high
      proportion of hyphal-specific genes (HSGs; HWP1, HYR1, ECE1, others), revealing a
      direct link between Sfl2p and hyphal development. Data mining pointed to a
      regulatory network in which Sfl1p and Sfl2p act as both transcriptional
      activators and repressors. Sfl1p directly represses the expression of positive
      regulators of hyphal growth (BRG1, UME6, TEC1, SFL2), while upregulating both
      yeast form-associated genes (RME1, RHD1, YWP1) and repressors of morphogenesis
      (SSN6, NRG1). On the other hand, Sfl2p directly upregulates HSGs and activators
      of hyphal growth (UME6, TEC1), while downregulating yeast form-associated genes
      and repressors of morphogenesis (NRG1, RFG1, SFL1). Using genetic interaction
      analyses, we provide further evidences that Sfl1p and Sfl2p antagonistically
      control C. albicans morphogenesis through direct modulation of the expression of
      important regulators of hyphal growth. Bioinformatic analyses suggest that
      binding of Sfl1p and Sfl2p to their targets occurs with the co-binding of Efg1p
      and/or Ndt80p. We show, indeed, that Sfl1p and Sfl2p targets are bound by Efg1p
      and that both Sfl1p and Sfl2p associate in vivo with Efg1p. Taken together, our
      data suggest that Sfl1p and Sfl2p act as central "switch on/off" proteins to
      coordinate the regulation of C. albicans morphogenesis.

PMID- 23966856
TI  - The smallest capsid protein mediates binding of the essential tegument protein
      pp150 to stabilize DNA-containing capsids in human cytomegalovirus.
AB  - Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that causes birth
      defects in newborns and life-threatening complications in immunocompromised
      individuals. Among all human herpesviruses, HCMV contains a much larger dsDNA
      genome within a similarly-sized capsid compared to the others, and it was
      proposed to require pp150, a tegument protein only found in cytomegaloviruses, to
      stabilize its genome-containing capsid. However, little is known about how pp150
      interacts with the underlying capsid. Moreover, the smallest capsid protein
      (SCP), while dispensable in herpes simplex virus type 1, was shown to play
      essential, yet undefined, role in HCMV infection. Here, by cryo electron
      microscopy (cryoEM), we determine three-dimensional structures of HCMV capsid (no
      pp150) and virion (with pp150) at sub-nanometer resolution. Comparison of these
      two structures reveals that each pp150 tegument density is composed of two helix
      bundles connected by a long central helix. Correlation between the resolved
      helices and sequence-based secondary structure prediction maps the tegument
      density to the N-terminal half of pp150. The structures also show that SCP
      mediates interactions between the capsid and pp150 at the upper helix bundle of
      pp150. Consistent with this structural observation, ribozyme inhibition of SCP
      expression in HCMV-infected cells impairs the formation of DNA-containing viral
      particles and reduces viral yield by 10,000 fold. By cryoEM reconstruction of the
      resulting "SCP-deficient" viral particles, we further demonstrate that SCP is
      required for pp150 functionally binding to the capsid. Together, our structural
      and biochemical results point to a mechanism whereby SCP recruits pp150 to
      stabilize genome-containing capsid for the production of infectious HCMV virion.

PMID- 23966857
TI  - MAP kinase phosphatase-2 plays a key role in the control of infection with
      Toxoplasma gondii by modulating iNOS and arginase-1 activities in mice.
AB  - The dual specific phosphatase, MAP kinase phosphatase-2 (MKP-2) has recently been
      demonstrated to negatively regulate macrophage arginase-1 expression, while at
      the same time to positively regulate iNOS expression. Consequently, MKP-2 is
      likely to play a significant role in the host interplay with intracellular
      pathogens. Here we demonstrate that MKP-2(-/-) mice on the C57BL/6 background
      have enhanced susceptibility compared with wild-type counterparts following
      infection with type-2 strains of Toxoplasma gondii as measured by increased
      parasite multiplication during acute infection, increased mortality from day 12
      post-infection onwards and increased parasite burdens in the brain, day 30 post
      infection. MKP-2(-/-) mice did not, however, demonstrate defective type-1
      responses compared with MKP-2(+/+) mice following infection although they did
      display significantly reduced serum nitrite levels and enhanced tissue arginase-1
      expression. Early resistance to T. gondii in MKP-2(+/+), but not MKP-2(-/-), mice
      was nitric oxide (NO) dependent as infected MKP-2(+/+), but not MKP-2(-/-) mice
      succumbed within 10 days post-infection with increased parasite burdens following
      treatment with the iNOS inhibitor L-NAME. Conversely, treatment of infected MKP
      2(-/-) but not MKP-2(+/+) mice with nor-NOHA increased parasite burdens
      indicating a protective role for arginase-1 in MKP-2(-/-) mice. In vitro studies
      using tachyzoite-infected bone marrow derived macrophages and selective
      inhibition of arginase-1 and iNOS activities confirmed that both iNOS and
      arginase-1 contributed to inhibiting parasite replication. However, the effects
      of arginase-1 were transient and ultimately the role of iNOS was paramount in
      facilitating long-term inhibition of parasite multiplication within macrophages.

PMID- 23966858
TI  - The role of selection in shaping diversity of natural M. tuberculosis
      populations.
AB  - Mycobacterium tuberculosis (M.tb), the cause of tuberculosis (TB), is estimated
      to infect a new host every second. While analyses of genetic data from natural
      populations of M.tb have emphasized the role of genetic drift in shaping patterns
      of diversity, the influence of natural selection on this successful pathogen is
      less well understood. We investigated the effects of natural selection on
      patterns of diversity in 63 globally extant genomes of M.tb and related
      pathogenic mycobacteria. We found evidence of strong purifying selection, with an
      estimated genome-wide selection coefficient equal to -9.5 * 10(-4) (95% CI -1.1 *
      10(-3) to -6.8 * 10(-4)); this is several orders of magnitude higher than recent
      estimates for eukaryotic and prokaryotic organisms. We also identified different
      patterns of variation across categories of gene function. Genes involved in
      transport and metabolism of inorganic ions exhibited very low levels of non
      synonymous polymorphism, equivalent to categories under strong purifying
      selection (essential and translation-associated genes). The highest levels of non
      synonymous variation were seen in a group of transporter genes, likely due to
      either diversifying selection or local selective sweeps. In addition to
      selection, we identified other important influences on M.tb genetic diversity,
      such as a 25-fold expansion of global M.tb populations coincident with explosive
      growth in human populations (estimated timing 1684 C.E., 95% CI 1620-1713 C.E.).
      These results emphasize the parallel demographic histories of this obligate
      pathogen and its human host, and suggest that the dominant effect of selection on
      M.tb is removal of novel variants, with exceptions in an interesting group of
      genes involved in transportation and defense. We speculate that the hostile
      environment within a host imposes strict demands on M.tb physiology, and thus a
      substantial fitness cost for most new mutations. In this respect, obligate
      bacterial pathogens may differ from other host-associated microbes such as
      symbionts.

PMID- 23966859
TI  - Local CD4 and CD8 T-cell reactivity to HSV-1 antigens documents broad viral
      protein expression and immune competence in latently infected human trigeminal
      ganglia.
AB  - Herpes simplex virus type 1 (HSV-1) infection results in lifelong chronic
      infection of trigeminal ganglion (TG) neurons, also referred to as neuronal HSV-1
      latency, with periodic reactivation leading to recrudescent herpetic disease in
      some persons. HSV-1 proteins are expressed in a temporally coordinated fashion
      during lytic infection, but their expression pattern during latent infection is
      largely unknown. Selective retention of HSV-1 reactive T-cells in human TG
      suggests their role in controlling reactivation by recognizing locally expressed
      HSV-1 proteins. We characterized the HSV-1 proteins recognized by virus-specific
      CD4 and CD8 T-cells recovered from human HSV-1-infected TG. T-cell clusters,
      consisting of both CD4 and CD8 T-cells, surrounded neurons and expressed mRNAs
      and proteins consistent with in situ antigen recognition and antiviral function.
      HSV-1 proteome-wide scans revealed that intra-TG T-cell responses included both
      CD4 and CD8 T-cells directed to one to three HSV-1 proteins per person. HSV-1
      protein ICP6 was targeted by CD8 T-cells in 4 of 8 HLA-discordant donors. In situ
      tetramer staining demonstrated HSV-1-specific CD8 T-cells juxtaposed to TG
      neurons. Intra-TG retention of virus-specific CD4 T-cells, validated to the HSV-1
      peptide level, implies trafficking of viral proteins from neurons to HLA class II
      expressing non-neuronal cells for antigen presentation. The diversity of viral
      proteins targeted by TG T-cells across all kinetic and functional classes of
      viral proteins suggests broad HSV-1 protein expression, and viral antigen
      processing and presentation, in latently infected human TG. Collectively, the
      human TG represents an immunocompetent environment for both CD4 and CD8 T-cell
      recognition of HSV-1 proteins expressed during latent infection. HSV-1 proteins
      recognized by TG-resident T-cells, particularly ICP6 and VP16, are potential HSV
      1 vaccine candidates.

PMID- 23966860
TI  - A compact viral processing proteinase/ubiquitin hydrolase from the OTU family.
AB  - Turnip yellow mosaic virus (TYMV)--a member of the alphavirus-like supergroup of
      viruses--serves as a model system for positive-stranded RNA virus membrane-bound
      replication. TYMV encodes a precursor replication polyprotein that is processed
      by the endoproteolytic activity of its internal cysteine proteinase domain (PRO).
      We recently reported that PRO is actually a multifunctional enzyme with a
      specific ubiquitin hydrolase (DUB) activity that contributes to viral
      infectivity. Here, we report the crystal structure of the 150-residue PRO.
      Strikingly, PRO displays no homology to other processing proteinases from
      positive-stranded RNA viruses, including that of alphaviruses. Instead, the
      closest structural homologs of PRO are DUBs from the Ovarian tumor (OTU) family.
      In the crystal, one molecule's C-terminus inserts into the catalytic cleft of the
      next, providing a view of the N-terminal product complex in replication
      polyprotein processing. This allows us to locate the specificity determinants of
      PRO for its proteinase substrates. In addition to the catalytic cleft, at the
      exit of which the active site is unusually pared down and solvent-exposed, a key
      element in molecular recognition by PRO is a lobe N-terminal to the catalytic
      domain. Docking models and the activities of PRO and PRO mutants in a
      deubiquitylating assay suggest that this N-terminal lobe is also likely involved
      in PRO's DUB function. Our data thus establish that DUBs can evolve to
      specifically hydrolyze both iso- and endopeptide bonds with different sequences.
      This is achieved by the use of multiple specificity determinants, as recognition
      of substrate patches distant from the cleavage sites allows a relaxed specificity
      of PRO at the sites themselves. Our results thus shed light on how such a compact
      protein achieves a diversity of key functions in viral genome replication and
      host-pathogen interaction.

PMID- 23966861
TI  - Francisella tularensis harvests nutrients derived via ATG5-independent autophagy
      to support intracellular growth.
AB  - Francisella tularensis is a highly virulent intracellular pathogen that invades
      and replicates within numerous host cell types including macrophages, hepatocytes
      and pneumocytes. By 24 hours post invasion, F. tularensis replicates up to 1000
      fold in the cytoplasm of infected cells. To achieve such rapid intracellular
      proliferation, F. tularensis must scavenge large quantities of essential carbon
      and energy sources from the host cell while evading anti-microbial immune
      responses. We found that macroautophagy, a eukaryotic cell process that primarily
      degrades host cell proteins and organelles as well as intracellular pathogens,
      was induced in F. tularensis infected cells. F. tularensis not only survived
      macroautophagy, but optimal intracellular bacterial growth was found to require
      macroautophagy. Intracellular growth upon macroautophagy inhibition was rescued
      by supplying excess nonessential amino acids or pyruvate, demonstrating that
      autophagy derived nutrients provide carbon and energy sources that support F.
      tularensis proliferation. Furthermore, F. tularensis did not require canonical,
      ATG5-dependent autophagy pathway induction but instead induced an ATG5
      independent autophagy pathway. ATG5-independent autophagy induction caused the
      degradation of cellular constituents resulting in the release of nutrients that
      the bacteria harvested to support bacterial replication. Canonical macroautophagy
      limits the growth of several different bacterial species. However, our data
      demonstrate that ATG5-independent macroautophagy may be beneficial to some
      cytoplasmic bacteria by supplying nutrients to support bacterial growth.

PMID- 23966862
TI  - Coronaviruses lacking exoribonuclease activity are susceptible to lethal
      mutagenesis: evidence for proofreading and potential therapeutics.
AB  - No therapeutics or vaccines currently exist for human coronaviruses (HCoVs). The
      Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV) epidemic in
      2002-2003, and the recent emergence of Middle East Respiratory Syndrome
      coronavirus (MERS-CoV) in April 2012, emphasize the high probability of future
      zoonotic HCoV emergence causing severe and lethal human disease. Additionally,
      the resistance of SARS-CoV to ribavirin (RBV) demonstrates the need to define new
      targets for inhibition of CoV replication. CoVs express a 3'-to-5'
      exoribonuclease in nonstructural protein 14 (nsp14-ExoN) that is required for
      high-fidelity replication and is conserved across the CoV family. All genetic and
      biochemical data support the hypothesis that nsp14-ExoN has an RNA proofreading
      function. Thus, we hypothesized that ExoN is responsible for CoV resistance to
      RNA mutagens. We demonstrate that while wild-type (ExoN+) CoVs were resistant to
      RBV and 5-fluorouracil (5-FU), CoVs lacking ExoN activity (ExoN-) were up to 300
      fold more sensitive. While the primary antiviral activity of RBV against CoVs was
      not mutagenesis, ExoN- CoVs treated with 5-FU demonstrated both enhanced
      sensitivity during multi-cycle replication, as well as decreased specific
      infectivity, consistent with 5-FU functioning as a mutagen. Comparison of full
      genome next-generation sequencing of 5-FU treated SARS-CoV populations revealed a
      16-fold increase in the number of mutations within the ExoN- population as
      compared to ExoN+. Ninety percent of these mutations represented A:G and U:C
      transitions, consistent with 5-FU incorporation during RNA synthesis. Together
      our results constitute direct evidence that CoV ExoN activity provides a critical
      proofreading function during virus replication. Furthermore, these studies
      identify ExoN as the first viral protein distinct from the RdRp that determines
      the sensitivity of RNA viruses to mutagens. Finally, our results show the
      importance of ExoN as a target for inhibition, and suggest that small-molecule
      inhibitors of ExoN activity could be potential pan-CoV therapeutics in
      combination with RBV or RNA mutagens.

PMID- 23966863
TI  - The viral KSHV chemokine vMIP-II inhibits the migration of Naive and activated
      human NK cells by antagonizing two distinct chemokine receptors.
AB  - Natural killer (NK) cells are innate immune cells able to rapidly kill virus
      infected and tumor cells. Two NK cell populations are found in the blood; the
      majority (90%) expresses the CD16 receptor and also express the CD56 protein in
      intermediate levels (CD56(Dim) CD16(Pos)) while the remaining 10% are CD16
      negative and express CD56 in high levels (CD56(Bright) CD16(Neg)). NK cells also
      reside in some tissues and traffic to various infected organs through the usage
      of different chemokines and chemokine receptors. Kaposi's sarcoma-associated
      herpesvirus (KSHV) is a human virus that has developed numerous sophisticated and
      versatile strategies to escape the attack of immune cells such as NK cells. Here,
      we investigate whether the KSHV derived cytokine (vIL-6) and chemokines (vMIP-I,
      vMIP-II, vMIP-III) affect NK cell activity. Using transwell migration assays,
      KSHV infected cells, as well as fusion and recombinant proteins, we show that out
      of the four cytokine/chemokines encoded by KSHV, vMIP-II is the only one that
      binds to the majority of NK cells, affecting their migration. We demonstrate that
      vMIP-II binds to two different receptors, CX3CR1 and CCR5, expressed by naive
      CD56(Dim) CD16(Pos) NK cells and activated NK cells, respectively. Furthermore,
      we show that the binding of vMIP-II to CX3CR1 and CCR5 blocks the binding of the
      natural ligands of these receptors, Fractalkine (Fck) and RANTES, respectively.
      Finally, we show that vMIP-II inhibits the migration of naive and activated NK
      cells towards Fck and RANTES. Thus, we present here a novel mechanism in which
      KSHV uses a unique protein that antagonizes the activity of two distinct
      chemokine receptors to inhibit the migration of naive and activated NK cells.

PMID- 23966864
TI  - beta-Catenin-independent activation of TCF1/LEF1 in human hematopoietic tumor
      cells through interaction with ATF2 transcription factors.
AB  - The role of Wnt signaling in embryonic development and stem cell maintenance is
      well established and aberrations leading to the constitutive up-regulation of
      this pathway are frequent in several types of human cancers. Upon ligand-mediated
      activation, Wnt receptors promote the stabilization of beta-catenin, which
      translocates to the nucleus and binds to the T-cell factor/lymphoid enhancer
      factor (TCF/LEF) family of transcription factors to regulate the expression of
      Wnt target genes. When not bound to beta-catenin, the TCF/LEF proteins are
      believed to act as transcriptional repressors. Using a specific lentiviral
      reporter, we identified hematopoietic tumor cells displaying constitutive TCF/LEF
      transcriptional activation in the absence of beta-catenin stabilization.
      Suppression of TCF/LEF activity in these cells mediated by an inducible dominant
      negative TCF4 (DN-TCF4) inhibited both cell growth and the expression of Wnt
      target genes. Further, expression of TCF1 and LEF1, but not TCF4, stimulated
      TCF/LEF reporter activity in certain human cell lines independently of beta
      catenin. By a complementary approach in vivo, TCF1 mutants, which lacked the
      ability to bind to beta-catenin, induced Xenopus embryo axis duplication, a
      hallmark of Wnt activation, and the expression of the Wnt target gene Xnr3.
      Through generation of different TCF1-TCF4 fusion proteins, we identified three
      distinct TCF1 domains that participate in the beta-catenin-independent activity
      of this transcription factor. TCF1 and LEF1 physically interacted and
      functionally synergized with members of the activating transcription factor 2
      (ATF2) family of transcription factors. Moreover, knockdown of ATF2 expression in
      lymphoma cells phenocopied the inhibitory effects of DN-TCF4 on the expression of
      target genes associated with the Wnt pathway and on cell growth. Together, our
      findings indicate that, through interaction with ATF2 factors, TCF1/LEF1 promote
      the growth of hematopoietic malignancies in the absence of beta-catenin
      stabilization, thus establishing a new mechanism for TCF1/LEF1 transcriptional
      activity distinct from that associated with canonical Wnt signaling. 

PMID- 23966865
TI  - Integrated model of de novo and inherited genetic variants yields greater power
      to identify risk genes.
AB  - De novo mutations affect risk for many diseases and disorders, especially those
      with early-onset. An example is autism spectrum disorders (ASD). Four recent
      whole-exome sequencing (WES) studies of ASD families revealed a handful of novel
      risk genes, based on independent de novo loss-of-function (LoF) mutations falling
      in the same gene, and found that de novo LoF mutations occurred at a twofold
      higher rate than expected by chance. However successful these studies were, they
      used only a small fraction of the data, excluding other types of de novo
      mutations and inherited rare variants. Moreover, such analyses cannot readily
      incorporate data from case-control studies. An important research challenge in
      gene discovery, therefore, is to develop statistical methods that accommodate a
      broader class of rare variation. We develop methods that can incorporate WES data
      regarding de novo mutations, inherited variants present, and variants identified
      within cases and controls. TADA, for Transmission And De novo Association,
      integrates these data by a gene-based likelihood model involving parameters for
      allele frequencies and gene-specific penetrances. Inference is based on a
      Hierarchical Bayes strategy that borrows information across all genes to infer
      parameters that would be difficult to estimate for individual genes. In addition
      to theoretical development we validated TADA using realistic simulations
      mimicking rare, large-effect mutations affecting risk for ASD and show it has
      dramatically better power than other common methods of analysis. Thus TADA's
      integration of various kinds of WES data can be a highly effective means of
      identifying novel risk genes. Indeed, application of TADA to WES data from
      subjects with ASD and their families, as well as from a study of ASD subjects and
      controls, revealed several novel and promising ASD candidate genes with strong
      statistical support. 

PMID- 23966866
TI  - Mediator directs co-transcriptional heterochromatin assembly by RNA interference
      dependent and -independent pathways.
AB  - Heterochromatin at the pericentromeric repeats in fission yeast is assembled and
      spread by an RNAi-dependent mechanism, which is coupled with the transcription of
      non-coding RNA from the repeats by RNA polymerase II. In addition, Rrp6, a
      component of the nuclear exosome, also contributes to heterochromatin assembly
      and is coupled with non-coding RNA transcription. The multi-subunit complex
      Mediator, which directs initiation of RNA polymerase II-dependent transcription,
      has recently been suggested to function after initiation in processes such as
      elongation of transcription and splicing. However, the role of Mediator in the
      regulation of chromatin structure is not well understood. We investigated the
      role of Mediator in pericentromeric heterochromatin formation and found that
      deletion of specific subunits of the head domain of Mediator compromised
      heterochromatin structure. The Mediator head domain was required for Rrp6
      dependent heterochromatin nucleation at the pericentromere and for RNAi-dependent
      spreading of heterochromatin into the neighboring region. In the latter process,
      Mediator appeared to contribute to efficient processing of siRNA from transcribed
      non-coding RNA, which was required for efficient spreading of heterochromatin.
      Furthermore, the head domain directed efficient transcription in heterochromatin.
      These results reveal a pivotal role for Mediator in multiple steps of
      transcription-coupled formation of pericentromeric heterochromatin. This
      observation further extends the role of Mediator to co-transcriptional chromatin
      regulation. 

PMID- 23966868
TI  - Comparative genomic and functional analysis of 100 Lactobacillus rhamnosus
      strains and their comparison with strain GG.
AB  - Lactobacillus rhamnosus is a lactic acid bacterium that is found in a large
      variety of ecological habitats, including artisanal and industrial dairy
      products, the oral cavity, intestinal tract or vagina. To gain insights into the
      genetic complexity and ecological versatility of the species L. rhamnosus, we
      examined the genomes and phenotypes of 100 L. rhamnosus strains isolated from
      diverse sources. The genomes of 100 L. rhamnosus strains were mapped onto the L.
      rhamnosus GG reference genome. These strains were phenotypically characterized
      for a wide range of metabolic, antagonistic, signalling and functional
      properties. Phylogenomic analysis showed multiple groupings of the species that
      could partly be associated with their ecological niches. We identified 17 highly
      variable regions that encode functions related to lifestyle, i.e. carbohydrate
      transport and metabolism, production of mucus-binding pili, bile salt resistance,
      prophages and CRISPR adaptive immunity. Integration of the phenotypic and genomic
      data revealed that some L. rhamnosus strains possibly resided in multiple niches,
      illustrating the dynamics of bacterial habitats. The present study showed two
      distinctive geno-phenotypes in the L. rhamnosus species. The geno-phenotype A
      suggests an adaptation to stable nutrient-rich niches, i.e. milk-derivative
      products, reflected by the alteration or loss of biological functions associated
      with antimicrobial activity spectrum, stress resistance, adaptability and fitness
      to a distinctive range of habitats. In contrast, the geno-phenotype B displays
      adequate traits to a variable environment, such as the intestinal tract, in terms
      of nutrient resources, bacterial population density and host effects. 

PMID- 23966869
TI  - A model-based analysis of GC-biased gene conversion in the human and chimpanzee
      genomes.
AB  - GC-biased gene conversion (gBGC) is a recombination-associated process that
      favors the fixation of G/C alleles over A/T alleles. In mammals, gBGC is
      hypothesized to contribute to variation in GC content, rapidly evolving
      sequences, and the fixation of deleterious mutations, but its prevalence and
      general functional consequences remain poorly understood. gBGC is difficult to
      incorporate into models of molecular evolution and so far has primarily been
      studied using summary statistics from genomic comparisons. Here, we introduce a
      new probabilistic model that captures the joint effects of natural selection and
      gBGC on nucleotide substitution patterns, while allowing for correlations along
      the genome in these effects. We implemented our model in a computer program,
      called phastBias, that can accurately detect gBGC tracts about 1 kilobase or
      longer in simulated sequence alignments. When applied to real primate genome
      sequences, phastBias predicts gBGC tracts that cover roughly 0.3% of the human
      and chimpanzee genomes and account for 1.2% of human-chimpanzee nucleotide
      differences. These tracts fall in clusters, particularly in subtelomeric regions;
      they are enriched for recombination hotspots and fast-evolving sequences; and
      they display an ongoing fixation preference for G and C alleles. They are also
      significantly enriched for disease-associated polymorphisms, suggesting that they
      contribute to the fixation of deleterious alleles. The gBGC tracts provide a
      unique window into historical recombination processes along the human and
      chimpanzee lineages. They supply additional evidence of long-term conservation of
      megabase-scale recombination rates accompanied by rapid turnover of hotspots.
      Together, these findings shed new light on the evolutionary, functional, and
      disease implications of gBGC. The phastBias program and our predicted tracts are
      freely available. 

PMID- 23966870
TI  - Introns regulate gene expression in Cryptococcus neoformans in a Pab2p dependent
      pathway.
AB  - Most Cryptococccus neoformans genes are interrupted by introns, and alternative
      splicing occurs very often. In this study, we examined the influence of introns
      on C. neoformans gene expression. For most tested genes, elimination of introns
      greatly reduces mRNA accumulation. Strikingly, the number and the position of
      introns modulate the gene expression level in a cumulative manner. A screen for
      mutant strains able to express functionally an intronless allele revealed that
      the nuclear poly(A) binding protein Pab2 modulates intron-dependent regulation of
      gene expression in C. neoformans. PAB2 deletion partially restored accumulation
      of intronless mRNA. In addition, our results demonstrated that the essential
      nucleases Rrp44p and Xrn2p are implicated in the degradation of mRNA transcribed
      from an intronless allele in C. neoformans. Double mutant constructions and over
      expression experiments suggested that Pab2p and Xrn2p could act in the same
      pathway whereas Rrp44p appears to act independently. Finally, deletion of the
      RRP6 or the CID14 gene, encoding the nuclear exosome nuclease and the TRAMP
      complex associated poly(A) polymerase, respectively, has no effect on intronless
      allele expression. 

PMID- 23966867
TI  - Genome-wide association of body fat distribution in African ancestry populations
      suggests new loci.
AB  - Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR),
      is a marker of body fat distribution. Although obesity disproportionately affects
      minority populations, few studies have conducted genome-wide association study
      (GWAS) of fat distribution among those of predominantly African ancestry (AA). We
      performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591
      and 27,350 AA individuals, respectively. We identified loci associated with fat
      distribution in AA individuals using meta-analyses of GWA results for WC and WHR
      (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p
      values<5.0 * 10(-6) were followed-up (stage 2) in AA with WC and with WHR.
      Additionally, we interrogated genomic regions of previously identified European
      ancestry (EA) WHR loci among AA. In joint analysis of association results
      including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064
      at LHX2, p = 2.24*10(-8) for WC-adjusted-for-BMI, and rs6931262 at RREB1, p =
      2.48*10(-8) for WHR-adjusted-for-BMI. However, neither signal was genome-wide
      significant after double GC-correction (LHX2: p = 6.5 * 10(-8); RREB1: p = 5.7 *
      10(-8)). Six of fourteen previously reported loci for waist in EA populations
      were significant (p<0.05 divided by the number of independent SNPs within the
      region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2
      SSPN). Further, we observed associations with metabolic traits: rs13389219 at
      GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and
      rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we
      observed nominal evidence for sexual dimorphism, with stronger results in AA
      women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified
      two suggestive loci associated with fat distribution in AA populations in
      addition to confirming 6 loci previously identified in populations of EA. These
      findings reinforce the concept that there are fat distribution loci that are
      independent of generalized adiposity.

PMID- 23966871
TI  - Genetic circuits that govern bisexual and unisexual reproduction in Cryptococcus
      neoformans.
AB  - Cryptococcus neoformans is a human fungal pathogen with a defined sexual cycle.
      Nutrient-limiting conditions and pheromones induce a dimorphic transition from
      unicellular yeast to multicellular hyphae and the production of infectious
      spores. Sexual reproduction involves cells of either opposite (bisexual) or one
      (unisexual) mating type. Bisexual and unisexual reproduction are governed by
      shared components of the conserved pheromone-sensing Cpk1 MAPK signal
      transduction cascade and by Mat2, the major transcriptional regulator of the
      pathway. However, the downstream targets of the pathway are largely unknown, and
      homology-based approaches have failed to yield downstream transcriptional
      regulators or other targets. In this study, we applied insertional mutagenesis
      via Agrobacterium tumefaciens transkingdom DNA delivery to identify mutants with
      unisexual reproduction defects. In addition to elements known to be involved in
      sexual development (Crg1, Ste7, Mat2, and Znf2), three key regulators of sexual
      development were identified by our screen: Znf3, Spo11, and Ubc5. Spo11 and Ubc5
      promote sporulation during both bisexual and unisexual reproduction. Genetic and
      phenotypic analyses provide further evidence implicating both genes in the
      regulation of meiosis. Phenotypic analysis of sexual development showed that Znf3
      is required for hyphal development during unisexual reproduction and also plays a
      central role during bisexual reproduction. Znf3 promotes cell fusion and
      pheromone production through a pathway parallel to and independent of the
      pheromone signaling cascade. Surprisingly, Znf3 participates in transposon
      silencing during unisexual reproduction and may serve as a link between RNAi
      silencing and sexual development. Our studies illustrate the power of unbiased
      genetic screens to reveal both novel and conserved circuits that operate sexual
      reproduction. 

PMID- 23966872
TI  - Generation of tandem direct duplications by reversed-ends transposition of maize
      ac elements.
AB  - Tandem direct duplications are a common feature of the genomes of eukaryotes
      ranging from yeast to human, where they comprise a significant fraction of copy
      number variations. The prevailing model for the formation of tandem direct
      duplications is non-allelic homologous recombination (NAHR). Here we report the
      isolation of a series of duplications and reciprocal deletions isolated de novo
      from a maize allele containing two Class II Ac/Ds transposons. The
      duplication/deletion structures suggest that they were generated by alternative
      transposition reactions involving the termini of two nearby transposable
      elements. The deletion/duplication breakpoint junctions contain 8 bp target site
      duplications characteristic of Ac/Ds transposition events, confirming their
      formation directly by an alternative transposition mechanism. Tandem direct
      duplications and reciprocal deletions were generated at a relatively high
      frequency (~0.5 to 1%) in the materials examined here in which transposons are
      positioned nearby each other in appropriate orientation; frequencies would likely
      be much lower in other genotypes. To test whether this mechanism may have
      contributed to maize genome evolution, we analyzed sequences flanking Ac/Ds and
      other hAT family transposons and identified three small tandem direct
      duplications with the structural features predicted by the alternative
      transposition mechanism. Together these results show that some class II
      transposons are capable of directly inducing tandem sequence duplications, and
      that this activity has contributed to the evolution of the maize genome.

PMID- 23966873
TI  - QTL analysis of high thermotolerance with superior and downgraded parental yeast
      strains reveals new minor QTLs and converges on novel causative alleles involved
      in RNA processing.
AB  - Revealing QTLs with a minor effect in complex traits remains difficult. Initial
      strategies had limited success because of interference by major QTLs and
      epistasis. New strategies focused on eliminating major QTLs in subsequent mapping
      experiments. Since genetic analysis of superior segregants from natural diploid
      strains usually also reveals QTLs linked to the inferior parent, we have extended
      this strategy for minor QTL identification by eliminating QTLs in both parent
      strains and repeating the QTL mapping with pooled-segregant whole-genome sequence
      analysis. We first mapped multiple QTLs responsible for high thermotolerance in a
      natural yeast strain, MUCL28177, compared to the laboratory strain, BY4742. Using
      single and bulk reciprocal hemizygosity analysis we identified MKT1 and PRP42 as
      causative genes in QTLs linked to the superior and inferior parent, respectively.
      We subsequently downgraded both parents by replacing their superior allele with
      the inferior allele of the other parent. QTL mapping using pooled-segregant whole
      genome sequence analysis with the segregants from the cross of the downgraded
      parents, revealed several new QTLs. We validated the two most-strongly linked new
      QTLs by identifying NCS2 and SMD2 as causative genes linked to the superior
      downgraded parent and we found an allele-specific epistatic interaction between
      PRP42 and SMD2. Interestingly, the related function of PRP42 and SMD2 suggests an
      important role for RNA processing in high thermotolerance and underscores the
      relevance of analyzing minor QTLs. Our results show that identification of minor
      QTLs involved in complex traits can be successfully accomplished by crossing
      parent strains that have both been downgraded for a single QTL. This novel
      approach has the advantage of maintaining all relevant genetic diversity as well
      as enough phenotypic difference between the parent strains for the trait-of
      interest and thus maximizes the chances of successfully identifying additional
      minor QTLs that are relevant for the phenotypic difference between the original
      parents. 

PMID- 23966874
TI  - A flexible approach for the analysis of rare variants allowing for a mixture of
      effects on binary or quantitative traits.
AB  - Multiple rare variants either within or across genes have been hypothesised to
      collectively influence complex human traits. The increasing availability of high
      throughput sequencing technologies offers the opportunity to study the effect of
      rare variants on these traits. However, appropriate and computationally efficient
      analytical methods are required to account for collections of rare variants that
      display a combination of protective, deleterious and null effects on the trait.
      We have developed a novel method for the analysis of rare genetic variation in a
      gene, region or pathway that, by simply aggregating summary statistics at each
      variant, can: (i) test for the presence of a mixture of effects on a trait; (ii)
      be applied to both binary and quantitative traits in population-based and family
      based data; (iii) adjust for covariates to allow for non-genetic risk factors
      and; (iv) incorporate imputed genetic variation. In addition, for preliminary
      identification of promising genes, the method can be applied to association
      summary statistics, available from meta-analysis of published data, for example,
      without the need for individual level genotype data. Through simulation, we show
      that our method is immune to the presence of bi-directional effects, with no
      apparent loss in power across a range of different mixtures, and can achieve
      greater power than existing approaches as long as summary statistics at each
      variant are robust. We apply our method to investigate association of type-1
      diabetes with imputed rare variants within genes in the major histocompatibility
      complex using genotype data from the Wellcome Trust Case Control Consortium. 

PMID- 23966875
TI  - Associations of mitochondrial haplogroups b4 and e with biliary atresia and
      differential susceptibility to hydrophobic bile Acid.
AB  - Mitochondrial dysfunction has been implicated in the pathogenesis of biliary
      atresia (BA). This study aimed to determine whether a specific mitochondrial DNA
      haplogroup is implicated in the pathogenesis and prognosis of BA. We determined
      40 mitochondrial single nucleotide polymorphisms in 15 major mitochondrial
      haplogroups by the use of 24-plex PCR and fluorescent beads combined with
      sequence-specific oligonucleotide probes in 71 patients with BA and in 200
      controls in the Taiwanese population of ethnic Chinese background. The haplogroup
      B4 and E prevalence were significantly lower and higher respectively, in the
      patients with BA than in the controls (odds ratios, 0.82 [p = 0.007] and 7.36 [p
      = 0.032] respectively) in multivariate logistic-regression analysis. The 3-year
      survival rate with native liver was significantly lower in haplogroup E than the
      other haplogroups (P = 0.037). A cytoplasmic hybrid (cybrid) was obtained from
      human 143B osteosarcoma cells devoid of mtDNA (rho(0) cell) and was fused with
      specific mtDNA bearing E and B4 haplogroups donated by healthy Taiwanese
      subjects. Chenodeoxycholic acid treatment resulted in significantly lower free
      radical production, higher mitochondrial membrane potential, more viable cells,
      and fewer apoptotic cybrid B4 cells than parental 143B and cybrid E cells. Bile
      acid treatment resulted in a significantly greater protective mitochondrial
      reaction with significantly higher mitochondrial DNA copy number and mitofusin 1
      and 2 concentrations in cybrid B4 and parental cells than in cybrid E cells. The
      results of the study suggested that the specific mitochondrial DNA haplogroups B4
      and E were not only associated with lower and higher prevalence of BA
      respectively, in the study population, but also with differential susceptibility
      to hydrophobic bile acid in the cybrid harboring different haplogroups.

PMID- 23966876
TI  - Masculinization of gene expression is associated with exaggeration of male sexual
      dimorphism.
AB  - Gene expression differences between the sexes account for the majority of
      sexually dimorphic phenotypes, and the study of sex-biased gene expression is
      important for understanding the genetic basis of complex sexual dimorphisms.
      However, it has been difficult to test the nature of this relationship due to the
      fact that sexual dimorphism has traditionally been conceptualized as a dichotomy
      between males and females, rather than an axis with individuals distributed at
      intermediate points. The wild turkey (Meleagris gallopavo) exhibits just this
      sort of continuum, with dominant and subordinate males forming a gradient in male
      secondary sexual characteristics. This makes it possible for the first time to
      test the correlation between sex-biased gene expression and sexually dimorphic
      phenotypes, a relationship crucial to molecular studies of sexual selection and
      sexual conflict. Here, we show that subordinate male transcriptomes show striking
      multiple concordances with their relative phenotypic sexual dimorphism.
      Subordinate males were clearly male rather than intersex, and when compared to
      dominant males, their transcriptomes were simultaneously demasculinized for male
      biased genes and feminized for female-biased genes across the majority of the
      transcriptome. These results provide the first evidence linking sexually
      dimorphic transcription and sexually dimorphic phenotypes. More importantly, they
      indicate that evolutionary changes in sexual dimorphism can be achieved by
      varying the magnitude of sex-bias in expression across a large proportion of the
      coding content of a genome. 

PMID- 23966877
TI  - Binding of TFIIIC to sine elements controls the relocation of activity-dependent
      neuronal genes to transcription factories.
AB  - In neurons, the timely and accurate expression of genes in response to synaptic
      activity relies on the interplay between epigenetic modifications of histones,
      recruitment of regulatory proteins to chromatin and changes to nuclear structure.
      To identify genes and regulatory elements responsive to synaptic activation in
      vivo, we performed a genome-wide ChIPseq analysis of acetylated histone H3 using
      somatosensory cortex of mice exposed to novel enriched environmental (NEE)
      conditions. We discovered that Short Interspersed Elements (SINEs) located distal
      to promoters of activity-dependent genes became acetylated following exposure to
      NEE and were bound by the general transcription factor TFIIIC. Importantly, under
      depolarizing conditions, inducible genes relocated to transcription factories
      (TFs), and this event was controlled by TFIIIC. Silencing of the TFIIIC subunit
      Gtf3c5 in non-stimulated neurons induced uncontrolled relocation to TFs and
      transcription of activity-dependent genes. Remarkably, in cortical neurons,
      silencing of Gtf3c5 mimicked the effects of chronic depolarization, inducing a
      dramatic increase of both dendritic length and branching. These findings reveal a
      novel and essential regulatory function of both SINEs and TFIIIC in mediating
      gene relocation and transcription. They also suggest that TFIIIC may regulate the
      rearrangement of nuclear architecture, allowing the coordinated expression of
      activity-dependent neuronal genes. 

PMID- 23966878
TI  - A highly redundant gene network controls assembly of the outer spore wall in S.
      cerevisiae.
AB  - The spore wall of Saccharomyces cerevisiae is a multilaminar extracellular
      structure that is formed de novo in the course of sporulation. The outer layers
      of the spore wall provide spores with resistance to a wide variety of
      environmental stresses. The major components of the outer spore wall are the
      polysaccharide chitosan and a polymer formed from the di-amino acid dityrosine.
      Though the synthesis and export pathways for dityrosine have been described,
      genes directly involved in dityrosine polymerization and incorporation into the
      spore wall have not been identified. A synthetic gene array approach to identify
      new genes involved in outer spore wall synthesis revealed an interconnected
      network influencing dityrosine assembly. This network is highly redundant both
      for genes of different activities that compensate for the loss of each other and
      for related genes of overlapping activity. Several of the genes in this network
      have paralogs in the yeast genome and deletion of entire paralog sets is
      sufficient to severely reduce dityrosine fluorescence. Solid-state NMR analysis
      of partially purified outer spore walls identifies a novel component in spore
      walls from wild type that is absent in some of the paralog set mutants.
      Localization of gene products identified in the screen reveals an unexpected role
      for lipid droplets in outer spore wall formation. 

PMID- 23966879
TI  - Chromosomal copy number variation, selection and uneven rates of recombination
      reveal cryptic genome diversity linked to pathogenicity.
AB  - Pathogenic fungi constitute a growing threat to both plant and animal species on
      a global scale. Despite a clonal mode of reproduction dominating the population
      genetic structure of many fungi, putatively asexual species are known to adapt
      rapidly when confronted by efforts to control their growth and transmission.
      However, the mechanisms by which adaptive diversity is generated across a clonal
      background are often poorly understood. We sequenced a global panel of the
      emergent amphibian pathogen, Batrachochytrium dendrobatidis (Bd), to high depth
      and characterized rapidly changing features of its genome that we believe hold
      the key to the worldwide success of this organism. Our analyses show three
      processes that contribute to the generation of de novo diversity. Firstly, we
      show that the majority of wild isolates manifest chromosomal copy number
      variation that changes over short timescales. Secondly, we show that cryptic
      recombination occurs within all lineages of Bd, leading to large regions of the
      genome being in linkage equilibrium, and is preferentially associated with
      classes of genes of known importance for virulence in other pathosystems.
      Finally, we show that these classes of genes are under directional selection, and
      that this has predominantly targeted the Global Panzootic Lineage (BdGPL). Our
      analyses show that Bd manifests an unusually dynamic genome that may have been
      shaped by its association with the amphibian host. The rates of variation that we
      document likely explain the high levels of phenotypic variability that have been
      reported for Bd, and suggests that the dynamic genome of this pathogen has
      contributed to its success across multiple biomes and host-species. 

PMID- 23966880
TI  - A role for CF1A 3' end processing complex in promoter-associated transcription.
AB  - The Cleavage Factor 1A (CF1A) complex, which is required for the termination of
      transcription in budding yeast, occupies the 3' end of transcriptionally active
      genes. We recently demonstrated that CF1A subunits also crosslink to the 5' end
      of genes during transcription. The presence of CF1A complex at the promoter
      suggested its possible involvement in the initiation/reinitiation of
      transcription. To check this possibility, we performed transcription run-on
      assay, RNAP II-density ChIP and strand-specific RT-PCR analysis in a mutant of
      CF1A subunit Clp1. As expected, RNAP II read through the termination signal in
      the temperature-sensitive mutant of clp1 at elevated temperature. The
      transcription readthrough phenotype was accompanied by a decrease in the density
      of RNAP II in the vicinity of the promoter region. With the exception of TFIIB
      and TFIIF, the recruitment of the general transcription factors onto the
      promoter, however, remained unaffected in the clp1 mutant. These results suggest
      that the CF1A complex affects the recruitment of RNAP II onto the promoter for
      reinitiation of transcription. Simultaneously, an increase in synthesis of
      promoter-initiated divergent antisense transcript was observed in the clp1
      mutant, thereby implicating CF1A complex in providing directionality to the
      promoter-bound polymerase. Chromosome Conformation Capture (3C) analysis revealed
      a physical interaction of the promoter and terminator regions of a gene in the
      presence of a functional CF1A complex. Gene looping was completely abolished in
      the clp1 mutant. On the basis of these results, we propose that the CF1A
      dependent recruitment of RNAP II onto the promoter for reinitiation and the
      regulation of directionality of promoter-associated transcription are
      accomplished through gene looping. 

PMID- 23966881
TI  - Characterization of the p53 cistrome--DNA binding cooperativity dissects p53's
      tumor suppressor functions.
AB  - p53 protects us from cancer by transcriptionally regulating tumor suppressive
      programs designed to either prevent the development or clonal expansion of
      malignant cells. How p53 selects target genes in the genome in a context- and
      tissue-specific manner remains largely obscure. There is growing evidence that
      the ability of p53 to bind DNA in a cooperative manner prominently influences
      target gene selection with activation of the apoptosis program being completely
      dependent on DNA binding cooperativity. Here, we used ChIP-seq to comprehensively
      profile the cistrome of p53 mutants with reduced or increased cooperativity. The
      analysis highlighted a particular relevance of cooperativity for extending the
      p53 cistrome to non-canonical binding sequences characterized by deletions,
      spacer insertions and base mismatches. Furthermore, it revealed a striking
      functional separation of the cistrome on the basis of cooperativity; with low
      cooperativity genes being significantly enriched for cell cycle and high
      cooperativity genes for apoptotic functions. Importantly, expression of high but
      not low cooperativity genes was correlated with superior survival in breast
      cancer patients. Interestingly, in contrast to most p53-activated genes, p53
      repressed genes did not commonly contain p53 binding elements. Nevertheless, both
      the degree of gene activation and repression were cooperativity-dependent,
      suggesting that p53-mediated gene repression is largely indirect and mediated by
      cooperativity-dependently transactivated gene products such as CDKN1A, E2F7 and
      non-coding RNAs. Since both activation of apoptosis genes with non-canonical
      response elements and repression of pro-survival genes are crucial for p53's
      apoptotic activity, the cistrome analysis comprehensively explains why p53
      induced apoptosis, but not cell cycle arrest, strongly depends on the
      intermolecular cooperation of p53 molecules as a possible safeguard mechanism
      protecting from accidental cell killing. 

PMID- 23966882
TI  - Vitellogenin underwent subfunctionalization to acquire caste and behavioral
      specific expression in the harvester ant Pogonomyrmex barbatus.
AB  - The reproductive ground plan hypothesis (RGPH) proposes that the physiological
      pathways regulating reproduction were co-opted to regulate worker division of
      labor. Support for this hypothesis in honeybees is provided by studies
      demonstrating that the reproductive potential of workers, assessed by the levels
      of vitellogenin (Vg), is linked to task performance. Interestingly, contrary to
      honeybees that have a single Vg ortholog and potentially fertile nurses, the
      genome of the harvester ant Pogonomyrmex barbatus harbors two Vg genes (Pb_Vg1
      and Pb_Vg2) and nurses produce infertile trophic eggs. P. barbatus, thus,
      provides a unique model to investigate whether Vg duplication in ants was
      followed by subfunctionalization to acquire reproductive and non-reproductive
      functions and whether Vg reproductive function was co-opted to regulate behavior
      in sterile workers. To investigate these questions, we compared the expression
      patterns of P. barbatus Vg genes and analyzed the phylogenetic relationships and
      molecular evolution of Vg genes in ants. qRT-PCRs revealed that Pb_Vg1 is more
      highly expressed in queens compared to workers and in nurses compared to
      foragers. By contrast, the level of expression of Pb_Vg2 was higher in foragers
      than in nurses and queens. Phylogenetic analyses show that a first duplication of
      the ancestral Vg gene occurred after the divergence between the poneroid and
      formicoid clades and subsequent duplications occurred in the lineages leading to
      Solenopsis invicta, Linepithema humile and Acromyrmex echinatior. The initial
      duplication resulted in two Vg gene subfamilies preferentially expressed in
      queens and nurses (subfamily A) or in foraging workers (subfamily B). Finally,
      molecular evolution analyses show that the subfamily A experienced positive
      selection, while the subfamily B showed overall relaxation of purifying
      selection. Our results suggest that in P. barbatus the Vg gene underwent
      subfunctionalization after duplication to acquire caste- and behavior- specific
      expression associated with reproductive and non-reproductive functions,
      supporting the validity of the RGPH in ants. 

PMID- 23966883
TI  - Past visits present: TCF/LEFs partner with ATFs for beta-catenin-independent
      activity.

PMID- 23966884
TI  - Multiple views to address diversity issues: an initial dialog to advance the
      chiropractic profession.
AB  - The purpose of this article is to provide expert viewpoints on the topic of
      diversity in the chiropractic profession, including cultural competency,
      diversity in the profession, educational and clinical practice strategies for
      addressing diversity, and workforce issues. Over the next decades, changing
      demographics in North America will alter how the chiropractic profession
      functions on many levels. As the population increases in diversity, we will need
      to prepare our workforce to meet the needs of future patients and society. 

PMID- 23966885
TI  - Teaching, leadership, scholarly productivity, and level of activity in the
      chiropractic profession: a study of graduates of the Los Angeles College of
      Chiropractic radiology residency program.
AB  - OBJECTIVE: The purpose of this study was to track the graduates of the Los
      Angeles College of Chiropractic (LACC) radiology residency program, review their
      scholarly productivity, and report those involved in teaching and leadership
      positions. METHODS: Former LACC residents' career information was identified
      through publicly available electronic documents including Web sites and social
      media. PubMed and the Index to Chiropractic Literature databases were searched
      for chiropractic graduate job surveys, and proportional comparisons were made
      between the career paths of LACC radiology residency graduates and those of non
      residency-trained chiropractors. RESULTS: Of 47 former LACC residents, 28 (60%)
      have or previously had careers in tertiary (chiropractic) education; and 12 (26%)
      have attained a department chair position or higher at tertiary teaching
      institutions. Twenty-two (47%) have or previously had private radiology
      practices, whereas 11 (23%) have or previously had clinical chiropractic
      practices. Often, residency graduates hold or have held 2 of these positions at
      once; and one, all 3. Chapters or books were authored by 13 (28%). CONCLUSION:
      Radiology residency LACC graduates are professionally active, particularly in
      education, and demonstrate scholarly productivity.

PMID- 23966886
TI  - Conventional medical attitudes to using a traditional medicine vodou-based model
      of pain management: survey of French dentists and the proposal of a pain model to
      facilitate integration.
AB  - OBJECTIVES: The purposes of this study were to develop a pain management model
      using traditional medicine (TM) vodou healing methods; to survey a sample of
      French dentists to rate components of conventional and proposed TM vodou-based
      pain management model; and to assess the possibility of conventional, allopathic
      providers to integrate TM or complementary and alternative medicine concepts.
      METHODS: From a set of 30 fact sheets collected from TM African healers (vodou
      healers), main clinical concepts and terminology were extracted. Twenty vodou
      based pain management concepts were collected from an interview with a TM vodou
      practitioner. From this information, a 7-step vodou-based pain management model
      was created. A sample of 40 French dentists from Nantes, France, whose practices
      focused on the clinical treatment of dental pain, was surveyed to assess the
      importance of both TM (vodou) and conventional biomedical components. RESULTS:
      Seventy percent of the dentists sampled rated the rational components of the TM
      model as "very important" or "important" for pain treatment, whereas 2 other
      traditional concepts were considered to be "supernatural" or beyond
      understanding. CONCLUSION: This study showed that traditional healers used
      conventional concepts and conventional practitioners could use traditional
      concepts. This suggests that conventional allopathic medical providers have the
      capacity to integrate biomedical concepts and other therapeutic and explanatory
      models. This information may be helpful to understand and improve risk management
      by anticipating and preventing potential reasons for failure in TM integration
      strategies and to enhance communication between patients, healers, and physicians
      to optimize TM or complementary and alternative medicine integration.

PMID- 23966887
TI  - The knowledge of our knowledge.
AB  - This classic article was published in the first volume and issue of Philosophical
      Constructs for the Chiropractic Profession. In this paper, Dr. McAndrews reviews
      the use of the term "philosophy" in chiropractic and urges the chiropractic
      profession to consider the use and misuse of this term. Reprinted with permission
      from McAndrews JF. The Knowledge of Our Knowledge. Philosophical Constructs for
      the Chiropractic Profession. 1991;1:14-17. 

PMID- 23966888
TI  - In response to "The Knowledge of Our Knowledge": 2 decades and not much has
      changed.
AB  - The chiropractic profession has struggled with how it is viewed and perceived by
      those within the profession and the powerful forces outside the profession. This
      commentary suggests that the vast majority of professional unrest is largely due
      to lines drawn upon philosophical boundaries and how we perceive what we know.
      For the profession to advance, it is imperative that unsubstantiated claims are
      eliminated from our justification for being and that we continue to test theories
      using scientific methods. Theories espoused must be able to be supported by valid
      research, and we must be ready to accept the results of these investigations and
      either build upon that body of research or accept the findings and move in
      alternative directions that science will take us. In doing so, we will contribute
      to the philosophy of health and perhaps help to change the health care paradigm
      from disease focused to wellness, which is based upon evidence and not emotion. 

PMID- 23966889
TI  - In response to "The Knowledge of Our Knowledge": a reflection on McAndrews' view
      of epistemology.
AB  - This commentary considers one of the articles published in the first volume of
      this journal and reflects on the status of research and knowledge at that time.
      The chiropractic profession has witnessed advancement in the use of the
      scientific method in the past several decades, and scholarly journals have helped
      support this substantial growth. 

PMID- 23966891
TI  - Brazilian kiss nightclub disaster.

PMID- 23966890
TI  - Probiotic Beverage with Soy Isoflavone Consumption for Breast Cancer Prevention:
      A Case-control Study.
AB  - The purpose of this study is to evaluate how beverages containing Lactobacillus
      casei Shirota (BLS) and soy isoflavone consumption since adolescence affected the
      incidence of breast cancer. In a population-based case-control study, three
      hundred and six cases with breast cancer and 662 controls aged 40 to 55 were
      matched for age and residential area and included in the analyses. Diet,
      lifestyle and other breast cancer risk factors were investigated using the self
      administered questionnaire and interview. Odds ratios (ORs) of BLS and soy
      isoflavone consumption for breast cancer incidence were independently and jointly
      estimated using a conditional logistic regression. The ORs of BLS consumption (>=
      four times a week against < four times a week) was 0.65 and statistically
      significant (p = 0.048). The analysis of association between soy consumption and
      breast cancer incidence showed the more the isoflavone consumption is, the lower
      the odds of breast cancer becomes. Adjusted ORs for breast cancer in the second,
      the third and the fourth quartiles of soy consumption against the first quartile
      were 0.76, 0.53 and 0.48, respectively (trend test, p = 0.0002). The BLS
      isoflavone interaction was not statistically significant; however, a biological
      interaction was suggested. Regular consumption of BLS and isoflavones since
      adolescence was inversely associated with the incidence of breast cancer in
      Japanese women.

PMID- 23966892
TI  - Nosocomial infections in burn patients: etiology, antimicrobial resistance, means
      to control.
AB  - The aim of our study was to determine the etiology of nosocomial infections,
      their changes over a period of five years (2007-2011), and the measures for
      control of infections and antimicrobial resistance in the Burns Clinic of the
      N.I. Pirogov University Multi-Profile Hospital for Active Treatment and Emergency
      Medicine, Sofia, Bulgaria. The medical records for all the patients and the
      database of the "Clinical Microbiology and Surveillance of Infections" National
      Information System were reviewed and analyzed to identify the microbial pathogens
      isolated in our burns Clinic. The three most frequent nosocomial pathogens were
      S. aureus, A. baumannii and P. aeruginosa. In order to control effectively
      nosocomial infections, a system of anti-infective and anti- microbial resistance
      measures has been developed and routinely implemented in our Clinic since 2008.
      Since 2009, thanks to this system, there has been a significant decrease in the
      rates of multi-resistant Staphylococcus aureus strains. Although at present the
      incidence of the nosocomial infections in our burns clinic is lower than in
      neighboring countries, several important infection control issues still need to
      be solved. We mainly rely on updating and strengthening the existing anti
      infective system in order to control the spread of multi-drug resistant
      organisms, such as A. baumannii, extended spectrum beta-lactamase-producing
      Enterobacteriaceae, and carbapenem-resistant P. aeruginosa. 

PMID- 23966893
TI  - Renal failure in burn patients: a review.
AB  - Burn care providers are usually challenged by multiple complications during the
      management of acute burns. One of the most common complications worldwide is
      renal failure. This article reviews the various aspects of renal failure
      management in burn patients. Two different types of renal failures develop in
      these patients. The different aetiological factors, incidence, suspected
      prognosis, ways of diagnosing, as well as prevention methods, and the most
      accepted treatment modalities are all discussed. A good understanding and an
      effective assessment of the problem help to reduce both morbidity and mortality
      in burn management. 

PMID- 23966895
TI  - The real expansion rate of meshers and micrografts: things we should keep in
      mind.
AB  - Skin graft expansion techniques (mesh and micrograft) are widely used, but there
      is ample evidence that skin graft meshers do not provide their claimed expansion
      rates. Although this finding might not be new for the majority of surgeons, less
      is known about surgeons' actual knowledge of expansion rates. The aim of this
      study was to evaluate the true expansion rates of commonly used expansion
      techniques with regard to claimed, achieved, and polled results. In the first
      part of the study, 54 surgeons were polled during an annual burns meeting
      regarding the most commonly used expansion techniques and expansion ratios; in
      the second step the true (achievable) expansion rates of the most widely used
      meshers and micrografts were analysed; and in third step, a poll involving 40
      surgeons was conducted to estimate the true expansion rates of the most
      frequently used skin expansion techniques. The skin meshers (1:1.5 / 1:3) did not
      achieve their claimed values: (1:1.5) 84.7% of the claimed expansion (mean +/-
      SD: 1:1.27 +/- 0.15) and (1:3) 53.1% of the 1:3 (1:1.59 +/- 0.15) mesher. The use
      of the micrografting technique resulted in 99.8% of the 1:3 (1:2.99 +/- 0.09),
      93.6% of the 1:4 (1:3.74 +/- 0.12) and 93.8% of the 1:6 (1:5.63 +/- 0.12) claimed
      expansion rates, respectively. In general the surgeons overestimated the
      achievable expansion rates. In general the achieved expansion rate was lower than
      the estimated and claimed expansion rates. The micrografting technique provided
      reliable and valid expansion rates compared to the skin meshers. We recommend
      using the micrograft technique when large expansion ratios are required, for
      example in severe extensive burns. 

PMID- 23966896
TI  - Parental authority to refuse acute burn treatment versus the protection our
      children deserve.
AB  - Our society has empowered parents to care for their children and take legally
      binding decisions on their behalf. One of the areas where such decision making is
      required is in medical care when a child's health is at stake. Three cases of
      child abuse and neglect were identified and reported. Literature searches were
      done to identify cases of child abuse in Kuwait using Medline and PubMed. News of
      child abuse was searched for using search engines (bbc.co.uk, cnn.com, and
      foxnews.com). The British Child Protection Act and the Kuwaiti Criminal
      Prosecution Code were studied. Child abuse and neglect exist in Kuwait and are
      probably underreported. The laws in Kuwait are designed to punish child abuse
      once it has occurred rather than aiming at preventing it. It is reported that 75%
      of those responsible for child abuse are the parents. They retain full authority
      to restrict medical access. Medical staff are offered very limited support and
      are restricted as to what they can achieve due to the Kuwaiti legal
      infrastructure, which should be amended so as to protect children rather than
      prosecute offenders. A local authority has to be established and empowered to
      investigate, report, and act when suspicions of child abuse arise. 

PMID- 23966894
TI  - Renal dysfunction in burns: a review.
AB  - Acute kidney injury (AKI), although rare, is a major complication of burn injury
      that commonly leads to mortality. It results from a complex interplay of various
      cellular and neuro-humoral changes affecting burn patients. Guidelines for the
      treatment of this entity are still not well defined; therefore, prevention and
      early diagnosis are key to avoid the unfavorable prognosis of AKI. These entail a
      comprehensive understanding of the global physiologic changes underlying the
      condition of burn patients and a judicious interpretation of their continuous
      homeostatic alterations. The aim of this review is to present the salient
      features in burn patient physiology that contribute to AKI. Strategies for
      identifying early AKI are presented. Finally, the different treatment modalities
      are revisited. 

PMID- 23966897
TI  - Outcomes of patients who commit suicide by burning.
AB  - Cases in which people use fire when attempting or committing suicide are not
      common but nevertheless constitute a cause of admission to burns units worldwide.
      Usually these people are suffering from stress and have been diagnosed as
      mentally ill. Schizophrenia, depression, and personality disorders are the most
      frequently diagnosed conditions. The psychological problems appear to have been
      overlooked by the family or not to have been presented to them. The aim of this
      study is to present the clinical features, characteristics, and outcomes of
      patients burned during a suicide attempt. The role of the psychiatrist is
      important, starting in the emergency room. The incidence of patients committing
      self-injury by burning appears to be higher in women burn patients. Deceased
      patients usually have a larger extent of burns and a higher incidence of other
      injuries and require more surgical procedures and longer hospitalization times.
      The problems for burn unit staff and qualified psychiatric care are discussed. 

PMID- 23966898
TI  - An unusual case of extensive self-inflicted cement burn.
AB  - Cement is a fine powder used to bind sand and stones into a matrix of concrete,
      making up the world's most frequently used building material in the construction
      industry. First described by Ramazzini in his book "De Morbis Artificia Diatriba"
      in 1700, the effect of cement on the skin was presumed to be due to contact
      dermatitis. The first cement burns case was published by Rowe and Williams in
      1963. Cement handling has been found to be responsible for many cases of
      occupational burns (generally full-thickness) usually affecting a limited TBSA,
      rarely greater than 5%, with localization especially in the lower limbs. We
      describe an unusual case of a self-inflicted cement burn involving 75% TBSA. A 28
      yr-old building worker attempted suicide by jumping into a cement mixer in a
      truck. Upon arrival at our burn centre, clinical examination revealed extensive
      burn (75% TBSA - 40% full-thickness) involving face, back, abdomen, upper limbs
      and circumferentially lower limbs, sparing the hands and feet. The patient was
      sedated, mechanically ventilated, and subjected to escharotomy of the lower limbs
      in the emergency room. The following day, the deep burns in the lower limbs were
      excised down to the fascia and covered with meshed allografts. Owing to probable
      intestinal and skin absorption of cement, metal toxicity was suspected and
      dialysis and forced diuresis were therefore initiated on day 3. The patient's
      clinical conditions gradually worsened and he died on day 13 from the multi-organ
      failure syndrome. 

PMID- 23966899
TI  - School fire in Iran: simple actions save lives.
AB  - On December 5, 2012 a fire broke out in a primary school in Iran, causing
      injuries to 26 children and two deaths. The fire came from an oil stove. Rather
      than evacuate the classroom and use the fire extinguisher, the teacher attempted
      to remove the stove itself from the classroom. During this process an explosion
      occurred resulting in a haphazard attempt at evacuation. This tragedy highlights
      gaps in both the policy and practice of fire safety. From 2005 to 2012, Iran
      experienced six large school fires that led to 67 injuries and five deaths. Five
      events were related to oil stoves. About 30% of Iran's classrooms use oil stoves
      for heating during the winter with 3.4 million students and 150,000 teachers at
      risk. Iran's Ministry of Education has mandated that regular training of school
      personnel in fire safety measures should be organized but no safety officer is
      tasked to prepare and conduct this training. Instead, the task is delegated to
      the Fire Departments, which fall under municipal administrations; however, such
      departments do not exist in 93% of the rural areas of Iran. School fires are not
      unique to Iran. Similar tragic events have occurred in several middle-income
      countries (India, Kenya, Russia) over the last decade. This article presents an
      overview of school fires in Iran and proposes preventive strategies through a
      reform in policy making and practice, including education of students and school
      personnel along with regular drills, designation of a fire safety officer, and
      development of a countrywide school fire registry. 

PMID- 23966901
TI  - MBC News.

PMID- 23966900
TI  - Primary triage of mass burn casualties with associated severe traumatic injuries.
AB  - A key aim in any mass disaster event is to avoid diverting resources by
      overwhelming specialized tertiary centers with minor casualties. The most crucial
      aspect of an effective disaster response is pre-hospital triage at the scene.
      Unfortunately, many triage systems have serious shortcomings in their
      methodologies and no existing triage system has enough scientific evidence to
      justify its universal adoption. Moreover, it is observed that the optimal
      approach to planning is by no means clear-cut and that each new incident
      involving burns appears to produce its own unique problems not all of which were
      predictable. In most major burns disasters, victims mostly have combined trauma
      burn injuries and form a heterogeneous group with a broad range of devastating
      injuries. Are these victims primarily burn patients or trauma patients? Should
      they be taken care of in a burn center or in a trauma center or only in a
      combined burns-trauma center? Who makes the decision? The present review is aimed
      at answering some of these questions. 

PMID- 23966902
TI  - Palladium Catalyzed Cyclopropanation of Unsaturated Endoperoxides. A New Peroxide
      Preserving Reaction.
AB  - Unsaturated bicyclic endoperoxides are efficiently cyclopropanated with excess
      diazomethane in the presence of catalytic Pd(OAc)2 in a stereoselective manner.
      This method represents a new peroxide preserving transformation. Whereas the
      unsaturated endoperoxides in the [2.2.1] series are attacked by the carbene from
      the exo face, the analogs with larger bridges are preferentially attacked from
      the face syn to the peroxo bridge. Only in the case of the benzannelated [2.2.2]
      system the attack occurs exclusively from the face proximal to the benzene ring.
      Certain strained cyclopropanated endoperoxides are reduced by diazomethane to
      give cis-diols. 1-Methylfuran endoperoxide gives rise to cis-1-formyl-2
      acetylcyclopropane in excellent yield.

PMID- 23966904
TI  - Progesterone inhibition of oxytocin signaling in endometrium.
AB  - Expression of the oxytocin receptor (OXTR) in the endometrium of ruminant species
      is regulated by the ovarian steroids progesterone (P) and estradiol (E). Near the
      end of the estrous cycle, long-term exposure of endometrial epithelial cells to P
      results in loss of genomic P receptors (PGRs), leading to an increase in E
      receptors (ERs). Genomic regulation of the OXTR is mediated via suppression of ER
      signaling by P. Upon OT binding at the plasma membrane of endometrial cells, a
      signaling cascade is generated stimulating release of prostaglandin F2alpha
      (PGF2alpha). Transport of PGF2alpha to the ovary results in release of OT by
      luteal cells in a positive feedback loop leading to luteal regression. This
      signaling cascade can be rapidly blocked by exposing endometrial cells to
      physiologic levels of P. This mini review will focus on the mechanisms by which P
      may act to block OXTR signaling and the luteolytic cascade in the ruminant
      endometrium, with special focus on both non-genomic signaling pathways and non
      receptor actions of P at the level of the plasma membrane. While this review
      focuses on ruminant species, non-classical blockage of OXTR signaling may be
      important for fertility in women. 

PMID- 23966903
TI  - Classification of schizophrenia patients based on resting-state functional
      network connectivity.
AB  - There is a growing interest in automatic classification of mental disorders based
      on neuroimaging data. Small training data sets (subjects) and very large amount
      of high dimensional data make it a challenging task to design robust and accurate
      classifiers for heterogeneous disorders such as schizophrenia. Most previous
      studies considered structural MRI, diffusion tensor imaging and task-based fMRI
      for this purpose. However, resting-state data has been rarely used in
      discrimination of schizophrenia patients from healthy controls. Resting data are
      of great interest, since they are relatively easy to collect, and not confounded
      by behavioral performance on a task. Several linear and non-linear classification
      methods were trained using a training dataset and evaluate with a separate
      testing dataset. Results show that classification with high accuracy is
      achievable using simple non-linear discriminative methods such as k-nearest
      neighbors (KNNs) which is very promising. We compare and report detailed results
      of each classifier as well as statistical analysis and evaluation of each single
      feature. To our knowledge our effects represent the first use of resting-state
      functional network connectivity (FNC) features to classify schizophrenia. 

PMID- 23966905
TI  - Acute and chronic glucocorticoid treatments regulate astrocyte-enriched mRNAs in
      multiple brain regions in vivo.
AB  - Previous studies have primarily interpreted gene expression regulation by
      glucocorticoids in the brain in terms of impact on neurons; however, less is
      known about the corresponding impact of glucocorticoids on glia and specifically
      astrocytes in vivo. Recent microarray experiments have identified glucocorticoid
      sensitive mRNAs in primary astrocyte cell culture, including a number of mRNAs
      that have reported astrocyte-enriched expression patterns relative to other brain
      cell types. Here, we have tested whether elevations of glucocorticoids regulate a
      subset of these mRNAs in vivo following acute and chronic corticosterone exposure
      in adult mice. Acute corticosterone exposure was achieved by a single injection
      of 10 mg/kg corticosterone, and tissue samples were harvested 2 h post-injection.
      Chronic corticosterone exposure was achieved by administering 10 mg/mL
      corticosterone via drinking water for 2 weeks. Gene expression was then assessed
      in two brain regions associated with glucocorticoid action (prefrontal cortex and
      hippocampus) by qPCR and by in situ hybridization. The majority of measured mRNAs
      regulated by glucocorticoids in astrocytes in vitro were similarly regulated by
      acute and/or chronic glucocorticoid exposure in vivo. In addition, the expression
      levels for mRNAs regulated in at least one corticosterone exposure condition
      (acute/chronic) demonstrated moderate positive correlation between the two
      conditions by brain region. In situ hybridization analyses suggest that select
      mRNAs are regulated by chronic corticosterone exposure specifically in astroctyes
      based on (1) similar general expression patterns between corticosterone-treated
      and vehicle-treated animals and (2) similar expression patterns to the pan
      astrocyte marker Aldh1l1. Our findings demonstrate that glucocorticoids regulate
      astrocyte-enriched mRNAs in vivo and suggest that glucocorticoids regulate gene
      expression in the brain in a cell type-dependent fashion. 

PMID- 23966907
TI  - Dopaminergic drug effects during reversal learning depend on anatomical
      connections between the orbitofrontal cortex and the amygdala.
AB  - Dopamine in the striatum is known to be important for reversal learning. However,
      the striatum does not act in isolation and reversal learning is also well
      accepted to depend on the orbitofrontal cortex (OFC) and the amygdala. Here we
      assessed whether dopaminergic drug effects on human striatal BOLD signaling
      during reversal learning is associated with anatomical connectivity in an
      orbitofrontal-limbic-striatal network, as measured with diffusion tensor imaging
      (DTI). By using a fiber-based approach, we demonstrate that dopaminergic drug
      effects on striatal BOLD signal varied as a function of fractional anisotropy
      (FA) in a pathway connecting the OFC with the amygdala. Moreover, our
      experimental design allowed us to establish that these white-matter dependent
      drug effects were mediated via D2 receptors. Thus, white matter dependent effects
      of the D2 receptor agonist bromocriptine on striatal BOLD signal were abolished
      by co-administration with the D2 receptor antagonist sulpiride. These data
      provide fundamental insight into the mechanism of action of dopaminergic drug
      effects during reversal learning. In addition, they may have important clinical
      implications by suggesting that white matter integrity can help predict
      dopaminergic drug effects on brain function, ultimately contributing to
      individual tailoring of dopaminergic drug treatment strategies in psychiatry. 

PMID- 23966906
TI  - Circannual changes in stress and feeding hormones and their effect on food
      seeking behaviors.
AB  - Seasonal fluctuations in food availability show a tight association with seasonal
      variations in body weight and food intake. Seasonal variations in food intake,
      energy storage, and expenditure appear to be a widespread phenomenon suggesting
      they may have evolved in anticipation for changing environmental demands. These
      cycles appear to be driven by changes in external daylength acting on
      neuroendocrine pathways. A number of neuroendocrine pathways, two of which are
      the endocrine mechanisms underlying feeding and stress, appear to show seasonal
      changes in both their circulating levels and reactivity. As such, variation in
      the level or reactivity to these hormones may be crucial factors in the control
      of seasonal variations in food-seeking behaviors. The present review examines the
      relationship between feeding behavior and seasonal changes in circulating
      hormones. We hypothesize that seasonal changes in circulating levels of
      glucocorticoids and the feeding-related hormones ghrelin and leptin contribute to
      seasonal fluctuations in feeding-related behaviors. This review will focus on the
      seasonal circulating levels of these hormones as well as sensitivity to these
      hormones in the modulation of food-seeking behaviors. 

PMID- 23966908
TI  - Mechanism based approaches for rescuing and enhancing cognition.
AB  - Progress toward pharmacological means for enhancing memory and cognition has been
      retarded by the widely discussed failure of behavioral studies in animals to
      predict human outcomes. As a result, a number of groups have targeted cognition
      related neurobiological mechanisms in animal models, with the assumption that
      these basic processes are highly conserved across mammals. Here we survey one
      such approach that begins with a form of synaptic plasticity intimately related
      to memory encoding in animals and likely operative in humans. An initial section
      will describe a detailed hypothesis concerning the signaling and structural
      events (a "substrate map") that convert learning associated patterns of afferent
      activity into extremely stable increases in fast, excitatory transmission. We
      next describe results suggesting that all instances of intellectual impairment so
      far tested in rodent models involve a common endpoint failure in the substrate
      map. This will be followed by a clinically plausible proposal for obviating the
      ultimate defect in these models. We then take up the question of whether it is
      reasonable to expect, from either general principles or a very limited set of
      experimental results, that enhancing memory will expand the cognitive
      capabilities of high functioning brains. The final section makes several
      suggestions about how to improve translation of behavioral results from animals
      to humans. Collectively, the material covered here points to the following: (1)
      enhancement, in the sense of rescue, is not an unrealistic possibility for a
      broad array of neuropsychiatric disorders; (2) serendipity aside, developing
      means for improving memory in normals will likely require integration of
      information about mechanisms with new behavioral testing strategies; (3) a shift
      in emphasis from synapses to networks is a next, logical step in the evolution of
      the cognition enhancement field. 

PMID- 23966909
TI  - Impact of trichostatin A and sodium valproate treatment on post-stroke
      neurogenesis and behavioral outcomes in immature mice.
AB  - Stroke in the neonatal brain frequently results in neurologic impairments
      including cognitive disability. We investigated the effect of long-term sodium
      valproate (valproate) and trichostatin A (TSA) treatment upon post-stroke
      neurogenesis in the dentate gyrus (DG) of stroke-injured immature mice. Decreased
      or abnormal integration of newborn DG neurons into hippocampal circuits can
      result in impaired visual-spatial function, abnormal modulation of mood-related
      behaviors, and the development of post-stroke epilepsy. Unilateral carotid
      ligation of P12 CD1 mice was followed by treatment with valproate, TSA, or
      vehicle for 2 weeks, bromodeoxyuridine (BrdU) administration for measurement of
      neurogenesis, and perfusion at P42 or P60. Behavior testing was conducted from
      P38-42. No detrimental effects on behavior testing were noted with TSA treatment,
      but mildly impaired cognitive function was noted with valproate-treated injured
      animals compared to normal animals. Significant increases in DG neurogenesis with
      both TSA and valproate treatment were noted with later administration of BrdU.
      Increased mortality and impaired weight gain was noted in the valproate-treated
      ligated animals, but not in the TSA-treated animals. In summary, the impact of
      histone deacetylase (HDAC) inhibition upon post-stroke subgranular zone
      neurogenesis is likely to depend on the age of the animal at the time point when
      neurogenesis is assessed, duration of HDAC inhibition before BrdU labeling,
      and/or the stage in the evolution of the injury. 

PMID- 23966910
TI  - Improved methods for chronic light-based motor mapping in mice: automated
      movement tracking with accelerometers, and chronic EEG recording in a bilateral
      thin-skull preparation.
AB  - Optogenetic stimulation of the mouse cortex can be used to generate motor maps
      that are similar to maps derived from electrode-based stimulation. Here we
      present a refined set of procedures for repeated light-based motor mapping in
      ChR2-expressing mice implanted with a bilateral thinned-skull chronic window and
      a chronically implanted electroencephalogram (EEG) electrode. Light stimulation
      is delivered sequentially to over 400 points across the cortex, and evoked
      movements are quantified on-line with a three-axis accelerometer attached to each
      forelimb. Bilateral maps of forelimb movement amplitude and movement direction
      were generated at weekly intervals after recovery from cranial window
      implantation. We found that light pulses of ~2 mW produced well-defined maps that
      were centered approximately 0.7 mm anterior and 1.6 mm lateral from bregma. Map
      borders were defined by sites where light stimulation evoked EEG deflections, but
      not movements. Motor maps were similar in size and location between mice, and
      maps were stable over weeks in terms of the number of responsive sites, and the
      direction of evoked movements. We suggest that our method may be used to
      chronically assess evoked motor output in mice, and may be combined with other
      imaging tools to assess cortical reorganization or sensory-motor integration. 

PMID- 23966911
TI  - Reorganization of neuronal circuits of the central olfactory system during
      postprandial sleep.
AB  - Plastic changes in neuronal circuits often occur in association with specific
      behavioral states. In this review, we focus on an emerging view that neuronal
      circuits in the olfactory system are reorganized along the wake-sleep cycle.
      Olfaction is crucial to sustaining the animals' life, and odor-guided behaviors
      have to be newly acquired or updated to successfully cope with a changing odor
      world. It is therefore likely that neuronal circuits in the olfactory system are
      highly plastic and undergo repeated reorganization in daily life. A remarkably
      plastic feature of the olfactory system is that newly generated neurons are
      continually integrated into neuronal circuits of the olfactory bulb (OB)
      throughout life. New neurons in the OB undergo an extensive selection process,
      during which many are eliminated by apoptosis for the fine tuning of neuronal
      circuits. The life and death decision of new neurons occurs extensively during a
      short time window of sleep after food consumption (postprandial sleep), a typical
      daily olfactory behavior. We review recent studies that explain how olfactory
      information is transferred between the OB and the olfactory cortex (OC) along the
      course of the wake-sleep cycle. Olfactory sensory input is effectively
      transferred from the OB to the OC during waking, while synchronized top-down
      inputs from the OC to the OB are promoted during the slow-wave sleep. We discuss
      possible neuronal circuit mechanisms for the selection of new neurons in the OB,
      which involves the encoding of olfactory sensory inputs and memory trace
      formation during waking and internally generated activities in the OC and OB
      during subsequent sleep. The plastic changes in the OB and OC are well
      coordinated along the course of olfactory behavior during wakefulness and
      postbehavioral rest and sleep. We therefore propose that the olfactory system
      provides an excellent model in which to understand behavioral state-dependent
      plastic mechanisms of the neuronal circuits in the brain. 

PMID- 23966912
TI  - Perirhinal cortical inactivation impairs object-in-place memory and disrupts task
      dependent firing in hippocampal CA1, but not in CA3.
AB  - Objects and their locations can associatively define an event and a conjoint
      representation of object-place can form an event memory. Remembering how to
      respond to a certain object in a spatial context is dependent on both hippocampus
      and perirhinal cortex (PER). However, the relative functional contributions of
      the two regions are largely unknown in object-place associative memory. We
      investigated the PER influence on hippocampal firing in a goal-directed object
      place memory task by comparing the firing patterns of CA1 and CA3 of the dorsal
      hippocampus between conditions of PER muscimol inactivation and vehicle control
      infusions. Rats were required to choose one of the two objects in a specific
      spatial context (regardless of the object positions in the context), which was
      shown to be dependent on both hippocampus and PER. Inactivation of PER with
      muscimol (MUS) severely disrupted performance of well-trained rats, resulting in
      response bias (i.e., choosing any object on a particular side). MUS did not
      significantly alter the baseline firing rates of hippocampal neurons. We measured
      the similarity in firing patterns between two trial conditions in which the same
      target objects were chosen on opposite sides within the same arm [object-in-place
      (O-P) strategy] and compared the results with the similarity in firing between
      two trial conditions in which the rat chose any object encountered on a
      particular side [response-in-place (R-P) strategy]. We found that the similarity
      in firing patterns for O-P trials was significantly reduced with MUS compared to
      control conditions (CTs). Importantly, this was largely because MUS injections
      affected the O-P firing patterns in CA1 neurons, but not in CA3. The results
      suggest that PER is critical for goal-directed organization of object-place
      associative memory in the hippocampus presumably by influencing how object
      information is associated with spatial information in CA1 according to task
      demand. 

PMID- 23966913
TI  - Decision-making in information seeking on texts: an eye-fixation-related
      potentials investigation.
AB  - Reading on a web page is known to be not linear and people need to make fast
      decisions about whether they have to stop or not reading. In such context,
      reading, and decision-making processes are intertwined and this experiment
      attempts to separate them through electrophysiological patterns provided by the
      Eye-Fixation-Related Potentials technique (EFRPs). We conducted an experiment in
      which EFRPs were recorded while participants read blocks of text that were
      semantically highly related, moderately related, and unrelated to a given goal.
      Participants had to decide as fast as possible whether the text was related or
      not to the semantic goal given at a prior stage. Decision making (stopping
      information search) may occur when the paragraph is highly related to the goal
      (positive decision) or when it is unrelated to the goal (negative decision).
      EFRPs were analyzed on and around typical eye fixations: either on words
      belonging to the goal (target), subjected to a high rate of positive decisions,
      or on low frequency unrelated words (incongruent), subjected to a high rate of
      negative decisions. In both cases, we found EFRPs specific patterns (amplitude
      peaking between 51 to 120 ms after fixation onset) spreading out on the next
      words following the goal word and the second fixation after an incongruent word,
      in parietal and occipital areas. We interpreted these results as delayed late
      components (P3b and N400), reflecting the decision to stop information searching.
      Indeed, we show a clear spill-over effect showing that the effect on word N
      spread out on word N + 1 and N + 2. 

PMID- 23966914
TI  - Directed forgetting in post-traumatic-stress-disorder: a study of refugee
      immigrants in Germany.
AB  - People with post-traumatic stress disorder (PTSD) often suffer from memory
      disturbances. In particular, previous studies suggest that PTSD patients perform
      atypically on tests of directed forgetting, which may be mediated by an altered
      emotional appraisal of the presented material. Also, a special role of
      dissociative symptoms in traumatized individuals' memory performance has been
      suggested. Here, we investigate these issues in traumatized immigrants in
      Germany. In an item-method directed forgetting task, pictures were presented
      individually, each followed by an instruction to either remember or forget it.
      Later, recognition memory was tested for all pictures, regardless of initial
      instruction. Overall, the PTSD group's discrimination accuracy was lower than the
      control group's, as PTSD participants produced fewer hits and more false alarms,
      but the groups did not differ in directed forgetting itself. Moreover, the more
      negatively participants evaluated the stimuli, the less they were able to
      discriminate old from new items. Participants with higher dissociation scores
      were particularly poor at recognizing to-be-forgotten items. Results confirm PTSD
      patients' general discrimination deficits, but provide no evidence for a distinct
      directed forgetting pattern in PTSD. Furthermore, data indicate that, in general,
      more negatively perceived items are discriminated with less accuracy than more
      positively appraised ones. Results are discussed in the larger context of emotion
      and stress-related modulations of episodic memory, with particular focus on the
      role of dissociative symptoms. 

PMID- 23966915
TI  - Co-segregation of hyperactivity, active coping styles, and cognitive dysfunction
      in mice selectively bred for low levels of anxiety.
AB  - We established mouse models of extremes in trait anxiety, which are based on
      selective breeding for low vs. normal vs. high open-arm exploration on the
      elevated plus-maze. Genetically selected low anxiety-related behavior (LAB)
      coincided with hyperactivity in the home cage. Given the fact that several
      psychiatric disorders such as schizophrenia, mania, and attention deficit
      hyperactivity disorder (ADHD) share hyperactivity symptom, we systematically
      examined LAB mice with respect to unique and overlapping endophenotypes of the
      three diseases. To this end Venn diagrams were used as an instrument for
      discrimination of possible models. We arranged the endophenotypes in Venn
      diagrams and translated them into different behavioral tests. LAB mice showed
      elevated levels of locomotion in the open field (OF) test with deficits in
      habituation, compared to mice bred for normal (NAB) and high anxiety-related
      behavior (HAB). Cross-breeding of hypoactive HAB and hyperactive LAB mice
      resulted in offspring showing a low level of locomotion comparable to HAB mice,
      indicating that the HAB alleles are dominant over LAB alleles in determining the
      level of locomotion. In a holeboard test, LAB mice spent less time in hole
      exploration, as shown in patients with schizophrenia and ADHD; however, LAB mice
      displayed no impairments in social interaction and prepulse inhibition (PPI),
      implying a unlikelihood of LAB as an animal model of schizophrenia. Although LAB
      mice displayed hyperarousal, active coping styles, and cognitive deficits,
      symptoms shared by mania and ADHD, they failed to reveal the classic manic
      endophenotypes, such as increased hedonia and object interaction. The neuroleptic
      haloperidol reduced locomotor activity in all mouse lines. The mood stabilizer
      lithium and the psychostimulant amphetamine, in contrast, selectively reduced
      hyperactivity in LAB mice. Based on the behavioral and pharmacological profiles,
      LAB mice are suggested as a novel rodent model of ADHD-like symptoms. 

PMID- 23966916
TI  - Explorations of object and location memory using fMRI.
AB  - Content-specific sub-systems of visual working memory (VWM) have been explored in
      many neuroimaging studies with inconsistent findings and procedures across
      experiments. The present study employed functional magnetic resonance imaging
      (fMRI) and a change detection task using a high number of trials and matched
      stimulus displays across object and location change (what vs. where) conditions.
      Furthermore, individual task periods were studied independently across conditions
      to identify differences corresponding to each task period. Importantly, this
      combination of task controls has not previously been described in the fMRI
      literature. Composite results revealed differential frontoparietal activation
      during each task period. A separation of object and location conditions yielded a
      distributed system of dorsal and ventral streams during the encoding of
      information corresponding to bilateral inferior parietal lobule (IPL) and lingual
      gyrus activation, respectively. Differential activity was also shown during the
      maintenance of information in middle frontal structures bilaterally for objects
      and the right IPL and left insula for locations. Together, these results reflect
      a domain-specific dissociation spanning several cortices and task periods.
      Furthermore, differential activations suggest a general caudal-rostral separation
      corresponding to object and location memory, respectively. 

PMID- 23966918
TI  - The episodicity of verbal reports of personally significant autobiographical
      memories: vividness correlates with narrative text quality more than with
      detailedness or memory specificity.
AB  - How can we tell from a memory report whether a memory is episodic or not?
      Vividness is required by many definitions, whereas detailedness, memory
      specificity, and narrative text type are competing definitions of episodicity
      used in research. We explored their correlations with vividness in personally
      significant autobiographical memories to provide evidence to support their
      relative claim to define episodic memories. In addition, we explored differences
      between different memory types and text types as well as between memories with
      different valences. We asked a lifespan sample (N = 168) of 8-, 12-, 16-, 20-, 40
      , and 65-year-olds of both genders (N = 27, 29, 27, 27, 28, 30) to provide brief
      oral life narratives. These were segmented into thematic memory units.
      Detailedness of person, place, and time did not correlate with each other or
      either vividness, memory specificity, or narrative text type. Narrative text
      type, in contrast, correlated both with vividness and memory specificity,
      suggesting narrative text type as a good criterion of episodicity. Emotionality
      turned out to be an even better predictor of vividness. Also, differences between
      narrative, chronicle, and argument text types and between specific versus more
      extended and atemporal memories were explored as well as differences between
      positive, negative, ambivalent, neutral, contamination, and redemption memory
      reports. It is concluded that temporal sequentiality is a central characteristic
      of episodic autobiographical memories. Furthermore, it is suggested that the
      textual quality of memory reports should be taken more seriously, and that
      evaluation and interpretation are inherent aspects of personally significant
      memories. 

PMID- 23966917
TI  - Neuregulin 1: a prime candidate for research into gene-environment interactions
      in schizophrenia? Insights from genetic rodent models.
AB  - Schizophrenia is a multi-factorial disease characterized by a high heritability
      and environmental risk factors. In recent years, an increasing number of
      researchers worldwide have started investigating the "two-hit hypothesis" of
      schizophrenia predicting that genetic and environmental risk factors (GxE)
      interactively cause the development of the disorder. This work is starting to
      produce valuable new animal models and reveal novel insights into the
      pathophysiology of schizophrenia. This mini review will focus on recent
      advancements in the field made by challenging mutant and transgenic rodent models
      for the schizophrenia candidate gene neuregulin 1 (NRG1) with particular
      environmental factors. It will outline results obtained from mouse and rat models
      for various Nrg1 isoforms/isoform types (e.g., transmembrane domain Nrg1, Type II
      Nrg1), which have been exposed to different forms of stress (acute versus
      chronic, restraint versus social) and housing conditions (standard laboratory
      versus minimally enriched housing). These studies suggest Nrg1 as a prime
      candidate for GxE interactions in schizophrenia rodent models and that the use of
      rodent models will enable a better understanding of GxE interactions and the
      underlying mechanisms. 

PMID- 23966919
TI  - Transcutaneous electrical nerve stimulation effects on neglect: a visual-evoked
      potential study.
AB  - We studied the effects of transcutaneous electrical nerve stimulation (TENS) in
      six right-brain-damaged patients with left unilateral spatial neglect (USN),
      using both standard clinical tests (reading, line, and letter cancelation, and
      line bisection), and electrophysiological measures (steady-state visual-evoked
      potentials, SSVEP). TENS was applied on left neck muscles for 15', and measures
      were recorded before, immediately after, and 60' after stimulation. Behavioral
      results showed that the stimulation temporarily improved the deficit in all
      patients. In cancelation tasks, omissions and performance asymmetries between the
      two hand-sides were reduced, as well as the rightward deviation in line
      bisection. Before TENS, SSVEP average latency to stimuli displayed in the left
      visual half-field [LVF (160 ms)] was remarkably longer than to stimuli shown in
      the right visual half-field [RVF (120 ms)]. Immediately after TENS, latency to
      LVF stimuli was 130 ms; 1 h after stimulation the effect of TENS faded, with
      latency returning to baseline. TENS similarly affected also the latency SSVEP of
      12 healthy participants, and their line bisection performance, with effects
      smaller in size. The present study, first, replicates evidence concerning the
      positive behavioral effects of TENS on the manifestations of left USN in right
      brain-damaged patients; second, it shows putatively related electrophysiological
      effects on the SSVEP latency. These behavioral and novel electrophysiological
      results are discussed in terms of specific directional effects of left
      somatosensory stimulation on egocentric coordinates, which in USN patients are
      displaced toward the side of the cerebral lesion. Showing that visual-evoked
      potentials latency is modulated by proprioceptive stimulation, we provide
      electrophysiological evidence to the effect that TENS may improve some
      manifestations of USN, with implications for its rehabilitation. 

PMID- 23966920
TI  - The human brain-from cells to society.
AB  - In December 2011, the European Science Foundation (ESF) brought together experts
      from a wide range of disciplines to discuss the issues that will influence the
      development of a healthier, more brain-aware European society. This perspective
      summarizes the main outcomes of that discussion and highlights important
      considerations to support improved mental health in Europe, including: The
      development of integrated neuropsychotherapeutic approaches to the treatment of
      psychiatric disorders.The development of more valid disease models for research
      into psychiatric disorders.An improved understanding of the relationship between
      biology and environment, particularly in relation to developmental plasticity and
      emerging pathology.More comparative studies to explore how scientific concepts
      relating to the human brain are received and understood in different
      sociocultural contexts.Research into the legal and ethical implications of recent
      developments in the brain sciences, including behavioral screening and
      manipulation, and emerging neurotechnologies. The broad geographical spread of
      the consulted experts across the whole of Europe, along with the wide range of
      disciplines they represent, gives these conclusions a strong scientific and pan
      European endorsement. The next step will be to look closely into these five
      selected topics, in terms of research strategy, science policy, societal
      implications, and legal and ethical frameworks. 

PMID- 23966921
TI  - Timing and awareness of movement decisions: does consciousness really come too
      late?
AB  - Since Libet's seminal observation that a brain potential related to movement
      preparation occurs before participants report to be aware of their movement
      intention, it has been debated whether consciousness has causal influence on
      movement decisions. Here we review recent advances that provide new insights into
      the dynamics of human decision-making and question the validity of different
      markers used for determining the onset of neural and conscious events. Motor
      decisions involve multiple stages of goal evaluation, intention formation, and
      action execution. While the validity of the Bereitschaftspotential (BP) as index
      of neural movement preparation is controversial, improved neural markers are able
      to predict decision outcome even at early stages. Participants report being
      conscious of their decisions only at the time of final intention formation, just
      before the primary motor cortex starts executing the chosen action. However,
      accumulating evidence suggests that this is an artifact of Libet's clock method
      used for assessing consciousness. More refined methods suggest that intention
      consciousness does not appear instantaneously but builds up progressively. In
      this view, early neural markers of decision outcome are not unconscious but
      simply reflect conscious goal evaluation stages which are not final yet and
      therefore not reported with the clock method. Alternatives to the Libet clock are
      discussed that might allow for assessment of consciousness during decision making
      with improved sensitivity to early decision stages and with less influence from
      meta-conscious and perceptual inferences. 

PMID- 23966922
TI  - Changes in brain activity of somatoform disorder patients during emotional
      empathy after multimodal psychodynamic psychotherapy.
AB  - Somatoform disorder patients show a variety of emotional disturbances including
      impaired emotion recognition and increased empathic distress. In a previous
      paper, our group showed that several brain regions involved in emotional
      processing, such as the parahippocampal gyrus and other regions, were less
      activated in pre-treatment somatoform disorder patients (compared to healthy
      controls) during an empathy task. Since the parahippocampal gyrus is involved in
      emotional memory, its decreased activation might reflect the repression of
      emotional memories (which-according to psychoanalytical concepts-plays an
      important role in somatoform disorder). Psychodynamic psychotherapy aims at
      increasing the understanding of emotional conflicts as well as uncovering
      repressed emotions. We were interested, whether brain activity in the
      parahippocampal gyrus normalized after (inpatient) multimodal psychodynamic
      psychotherapy. Using fMRI, subjects were scanned while they shared the emotional
      states of presented facial stimuli expressing anger, disgust, joy, and a neutral
      expression; distorted stimuli with unrecognizable content served as control
      condition. 15 somatoform disorder patients were scanned twice, pre and post
      multimodal psychodynamic psychotherapy; in addition, 15 age-matched healthy
      control subjects were investigated. Effects of psychotherapy on hemodynamic
      responses were analyzed implementing two approaches: (1) an a priori region of
      interest approach and (2) a voxelwise whole brain analysis. Both analyses
      revealed increased hemodynamic responses in the left and right parahippocampal
      gyrus (and other regions) after multimodal psychotherapy in the contrast "empathy
      with anger"-"control." Our results are in line with psychoanalytical concepts
      about somatoform disorder. They suggest the parahippocampal gyrus is crucially
      involved in the neurobiological mechanisms which underly the emotional deficits
      of somatoform disorder patients. 

PMID- 23966923
TI  - Non-invasive brain stimulation can induce paradoxical facilitation. Are these
      neuroenhancements transferable and meaningful to security services?
AB  - For ages, we have been looking for ways to enhance our physical and cognitive
      capacities in order to augment our security. One potential way to enhance our
      capacities may be to externally stimulate the brain. Methods of non-invasive
      brain stimulation (NIBS), such as repetitive transcranial magnetic stimulation
      (rTMS) and transcranial electrical stimulation (tES), have been recently
      developed to modulate brain activity. Both techniques are relatively safe and can
      transiently modify motor and cognitive functions outlasting the stimulation
      period. The purpose of this paper is to review data suggesting that NIBS can
      enhance motor and cognitive performance in healthy volunteers. We frame these
      findings in the context of whether they may serve security purposes.
      Specifically, we review studies reporting that NIBS induces paradoxical
      facilitation in motor (precision, speed, strength, acceleration endurance, and
      execution of daily motor task) and cognitive functions (attention, impulsive
      behavior, risk-taking, working memory, planning, and deceptive capacities).
      Although transferability and meaningfulness of these NIBS-induced paradoxical
      facilitations into real-life situations are not clear yet, NIBS may contribute at
      improving training of motor and cognitive functions relevant for military, civil,
      and forensic security services. This is an enthusiastic perspective that also
      calls for fair and open debates on the ethics of using NIBS in healthy
      individuals to enhance normal functions. 

PMID- 23966924
TI  - Improving the neural mechanisms of cognition through the pursuit of happiness.
AB  - This paper reviews evidence on the neural basis of how positive mood states can
      modulate cognition, particularly during creative problem-solving. Studies
      performed over the past few decades demonstrate that individuals in a positive
      mood engage in a broader scope of attention, enhancing their access to distant
      and unusual semantic associations, and increasing task-shifting and problem
      solving capacities. In this review, we summarize these behavioral studies; we
      then present recent findings on the changes in brain activation patterns that are
      induced by a positive mood when participants engage in problem-solving tasks and
      show how these relate to task performance. Additionally, we integrate findings on
      the neuromodulatory influence of positive mood on cognition as mediated by
      dopaminergic signaling in the prefrontal cortex and we describe how this system
      can go awry during pathological states of elevated mood as in mania. Finally, we
      describe current and future research directions using psychotherapeutic and real
      time fMRI neurofeedback approaches to up-regulate positive mood and facilitate
      optimal creative cognitive performance. We conclude with some speculations on the
      clinical implications of this emerging area of research. 

PMID- 23966925
TI  - Reconceptualizing functional brain connectivity in autism from a developmental
      perspective.
AB  - While there is almost universal agreement amongst researchers that autism is
      associated with alterations in brain connectivity, the precise nature of these
      alterations continues to be debated. Theoretical and empirical work is beginning
      to reveal that autism is associated with a complex functional phenotype
      characterized by both hypo- and hyper-connectivity of large-scale brain systems.
      It is not yet understood why such conflicting patterns of brain connectivity are
      observed across different studies, and the factors contributing to these
      heterogeneous findings have not been identified. Developmental changes in
      functional connectivity have received inadequate attention to date. We propose
      that discrepancies between findings of autism related hypo-connectivity and hyper
      connectivity might be reconciled by taking developmental changes into account. We
      review neuroimaging studies of autism, with an emphasis on functional magnetic
      resonance imaging studies of intrinsic functional connectivity in children,
      adolescents and adults. The consistent pattern emerging across several studies is
      that while intrinsic functional connectivity in adolescents and adults with
      autism is generally reduced compared with age-matched controls, functional
      connectivity in younger children with the disorder appears to be increased. We
      suggest that by placing recent empirical findings within a developmental
      framework, and explicitly characterizing age and pubertal stage in future work,
      it may be possible to resolve conflicting findings of hypo- and hyper
      connectivity in the extant literature and arrive at a more comprehensive
      understanding of the neurobiology of autism. 

PMID- 23966926
TI  - Is two better than one? Limb activation treatment combined with contralesional
      arm vibration to ameliorate signs of left neglect.
AB  - In the present study, we evaluated the effects of the Limb Activation Treatment
      (LAT) alone and in combination with the Contralateral Arm Vibration (CAV) on left
      neglect (LN) rehabilitation. We conceived them as techniques that both prompt the
      activation of the lesioned right hemisphere because of the activation (with the
      LAT as an active technique) and the stimulation (with the CAV as a passive
      technique) of the left hemibody. To test the effect of the simultaneous use of
      these two techniques (i.e., LAT and CAV) on visuo-spatial aspects of LN, we
      described the case of an LN patient (GR), who showed high intra-individual
      variability (IIV) in performance. Given the high IIV of GR, we used an ABAB
      repeated-measures design to better define the effectiveness of the combined
      application of LAT and CAV, as a function of time. The results showed an
      improvement of GR's performance on the Bells test following the combined
      application of LAT and CAV, with respect to the application of LAT alone. We did
      not find, however, significant effects of treatment on two other LN tests (i.e.,
      Line bisection and Picture scanning). We propose that the combined application of
      LAT and CAV can be beneficial for some aspects of LN. 

PMID- 23966927
TI  - Rostral and caudal prefrontal contribution to creativity: a meta-analysis of
      functional imaging data.
AB  - Creativity is of central importance for human civilization, yet its
      neurocognitive bases are poorly understood. The aim of the present study was to
      integrate existing functional imaging data by using the meta-analysis approach.
      We reviewed 34 functional imaging studies that reported activation foci during
      tasks assumed to engage creative thinking in healthy adults. A coordinate-based
      meta-analysis using Activation Likelihood Estimation (ALE) first showed a set of
      predominantly left-hemispheric regions shared by the various creativity tasks
      examined. These regions included the caudal lateral prefrontal cortex (PFC), the
      medial and lateral rostral PFC, and the inferior parietal and posterior temporal
      cortices. Further analyses showed that tasks involving the combination of remote
      information (combination tasks) activated more anterior areas of the lateral PFC
      than tasks involving the free generation of unusual responses (unusual generation
      tasks), although both types of tasks shared caudal prefrontal areas. In addition,
      verbal and non-verbal tasks involved the same regions in the left caudal
      prefrontal, temporal, and parietal areas, but also distinct domain-oriented
      areas. Taken together, these findings suggest that several frontal and parieto
      temporal regions may support cognitive processes shared by diverse creativity
      tasks, and that some regions may be specialized for distinct types of processes.
      In particular, the lateral PFC appeared to be organized along a rostro-caudal
      axis, with rostral regions involved in combining ideas creatively and more
      posterior regions involved in freely generating novel ideas. 

PMID- 23966928
TI  - On the relationship between anxiety and error monitoring: a meta-analysis and
      conceptual framework.
AB  - Research involving event-related brain potentials has revealed that anxiety is
      associated with enhanced error monitoring, as reflected in increased amplitude of
      the error-related negativity (ERN). The nature of the relationship between
      anxiety and error monitoring is unclear, however. Through meta-analysis and a
      critical review of the literature, we argue that anxious apprehension/worry is
      the dimension of anxiety most closely associated with error monitoring. Although,
      overall, anxiety demonstrated a robust, "small-to-medium" relationship with
      enhanced ERN (r = -0.25), studies employing measures of anxious apprehension show
      a threefold greater effect size estimate (r = -0.35) than those utilizing other
      measures of anxiety (r = -0.09). Our conceptual framework helps explain this more
      specific relationship between anxiety and enhanced ERN and delineates the unique
      roles of worry, conflict processing, and modes of cognitive control.
      Collectively, our analysis suggests that enhanced ERN in anxiety results from the
      interplay of a decrease in processes supporting active goal maintenance and a
      compensatory increase in processes dedicated to transient reactivation of task
      goals on an as-needed basis when salient events (i.e., errors) occur. 

PMID- 23966929
TI  - Structural neuroimaging of social cognition in progressive non-fluent aphasia and
      behavioral variant of frontotemporal dementia.
AB  - Social cognition impairments are pervasive in the frontotemporal dementias (FTD).
      These deficits would be triggered by (a) basic emotion and face recognition
      processes as well as by (b) higher level social cognition (e.g., theory of mind,
      ToM). Both emotional processing and social cognition impairments have been
      previously reported in the behavioral variant of FTD (bvFTD) and also in other
      versions of FTDs, including primary progressive aphasia. However, no
      neuroanatomic comparison between different FTD variants has been performed. We
      report selective behavioral impairments of face recognition, emotion recognition,
      and ToM in patients with bvFTD and progressive non-fluent aphasia (PNFA) when
      compared to controls. Voxel-based morphometry (VBM) shows a classical impairment
      of mainly orbitofrontal (OFC), anterior cingulate (ACC), insula and lateral
      temporal cortices in patients. Comparative analysis of regional gray matter
      related to social cognition deficits (VBM) reveals a differential pattern of
      fronto-insulo-temporal atrophy in bvFTD and an insulo-temporal involvement in
      PNFA group. Results suggest that in spite of similar social cognition impairments
      reported in bvFTD and PNFA, the former represents an inherent ToM affectation
      whereas in the PNFA these deficits could be related to more basic processes of
      face and emotion recognition. These results are interpreted in the frame of the
      fronto-insulo-temporal social context network model (SCNM). 

PMID- 23966930
TI  - Hypnosis as neurophenomenology.
AB  - Hypnosis research binds phenomenology and neuroscience. Here we show how recent
      evidence probing the impact of hypnosis and suggestion can inform and advance a
      neurophenomenological approach. In contrast to meditative practices that involve
      lengthy and intensive training, hypnosis induces profound alterations in
      subjective experience following just a few words of suggestion. Individuals
      highly responsive to hypnosis can quickly and effortlessly manifest atypical
      conscious experiences as well as override deeply entrenched processes. These
      capacities open new avenues for suspending habitual modes of attention and
      achieving refined states of meta-awareness. Furthermore, hypnosis research sheds
      light on the effects of suggestion, expectation, and interpersonal factors beyond
      the narrow context of hypnotic procedures. Such knowledge may help to further
      foster phenomenological interviewing methods, improve experiential reports, and
      elucidate the mechanisms of contemplative practices. Incorporating hypnosis and
      suggestion into the broader landscape of neurophenomenology, therefore, would
      likely help bridge subjective experience and third-person approaches to the mind.

PMID- 23966931
TI  - Feeling the pain of others is associated with self-other confusion and prior pain
      experience.
AB  - Some chronic pain patients and healthy individuals experience pain when observing
      injury or others in pain. To further understand shared pain, we investigated
      perspective taking, bodily ownership and tooth pain sensitivity. First,
      participants who reported shared pain (responders) and those who did not (non
      responders) viewed an avatar on a screen. Intermittently, 0-3 circles appeared.
      Sometimes the participant's and avatar's perspective were consistent, both
      directly viewed the same circles, and sometimes inconsistent, both directly
      viewed different circles. Responders were faster than non-responders to identify
      the number of circles when adopting a consistent perspective. Second,
      participants sat with their left hand hidden while viewing a rubber hand. All
      participants reported an illusory sensation of feeling stroking in the rubber
      hand and a sense of ownership of the rubber hand during synchronous stroking of
      the rubber and hidden hand. The responders also reported feeling the stroking and
      a sense of ownership of the rubber hand during asynchronous stroking. For
      experiment three, participants with either low, moderate, or high tooth
      sensitivity observed a series of images depicting someone eating an ice-popsicle.
      Low sensitivity participants never reported pain. In contrast, moderate and high
      sensitivity participants reported pain in response to an image depicting someone
      eating an ice popsicle (4 and 19% of the time, respectively) and depicting
      someone eating an ice-popsicle and expressing pain (23 and 40%, respectively). In
      summary, responders have reduced ability to distinguish their own and others'
      visual perspective and enhanced ability to integrate a foreign arm into their
      bodily representation. The tendency to share pain is also enhanced when an
      observed pain is commonly experienced by the observer. Shared pain may therefore
      involve reactivation of pain memories or pain schema that are readily integrated
      into a self perspective and bodily representation. 

PMID- 23966932
TI  - Unattended and attended visual change detection of motion as indexed by event
      related potentials and its behavioral correlates.
AB  - Visual mismatch negativity (vMMN) is a negative-going component amongst cognitive
      event-related potentials. It reflects an automatic change-detection process that
      occurs when an infrequent stimulus is presented that is incongruent with the
      representation of a frequent (standard) event. In our research we use visual
      motion (more specifically motion direction changes) to study vMMN. Since movement
      in the visual field is quite irresistible to our brain, the question in hand is,
      if the detection of motion direction changes is dependent on attention directed
      to the stimulus. We present a new continuous whole-display stimulus
      configuration, where the attention capturing primary task of motion onset
      detection is in the central part of the visual display and visual oddball
      sequence on the background. The visual oddball paradigm consisted of 85% standard
      and 15% deviant events, motion direction change being the deviant. We show that
      even though the unattended visual oddball sequence does not affect the
      performance in the demanding behavioral primary task, the differences appearing
      in that sequence are noticed by our brain and reflected in two distinguishable
      vMMN components in occipital and parietal scalp locations. When attention is
      directed toward the visual oddball sequence, we only see different processing of
      standards and deviants in later time-windows and task-related activity in frontal
      scalp location. Our results are obtained under strict attention manipulation
      conditions. 

PMID- 23966933
TI  - Control beliefs can predict the ability to up-regulate sensorimotor rhythm during
      neurofeedback training.
AB  - Technological progress in computer science and neuroimaging has resulted in many
      approaches that aim to detect brain states and translate them to an external
      output. Studies from the field of brain-computer interfaces (BCI) and
      neurofeedback (NF) have validated the coupling between brain signals and computer
      devices; however a cognitive model of the processes involved remains elusive.
      Psychological parameters usually play a moderate role in predicting the
      performance of BCI and NF users. The concept of a locus of control, i.e., whether
      one's own action is determined by internal or external causes, may help to
      unravel inter-individual performance capacities. Here, we present data from 20
      healthy participants who performed a feedback task based on EEG recordings of the
      sensorimotor rhythm (SMR). One group of 10 participants underwent 10 training
      sessions where the amplitude of the SMR was coupled to a vertical feedback bar.
      The other group of ten participants participated in the same task but relied on
      sham feedback. Our analysis revealed that a locus of control score focusing on
      control beliefs with regard to technology negatively correlated with the power of
      SMR. These preliminary results suggest that participants whose confidence in
      control over technical devices is high might consume additional cognitive
      resources. This higher effort in turn may interfere with brain states of
      relaxation as reflected in the SMR. As a consequence, one way to improve control
      over brain signals in NF paradigms may be to explicitly instruct users not to
      force mastery but instead to aim at a state of effortless relaxation. 

PMID- 23966934
TI  - Attention in the temporal domain: a phase-coding mechanism controls the gain of
      sensory processing.

PMID- 23966935
TI  - The potential of the human connectome as a biomarker of brain disease.
AB  - The human connectome at the level of fiber tracts between brain regions has been
      shown to differ in patients with brain disorders compared to healthy control
      groups. Nonetheless, there is a potentially large number of different network
      organizations for individual patients that could lead to cognitive deficits
      prohibiting correct diagnosis. Therefore changes that can distinguish groups
      might not be sufficient to diagnose the disease that an individual patient
      suffers from and to indicate the best treatment option for that patient. We
      describe the challenges introduced by the large variability of connectomes within
      healthy subjects and patients and outline three common strategies to use
      connectomes as biomarkers of brain diseases. Finally, we propose a fourth option
      in using models of simulated brain activity (the dynamic connectome) based on
      structural connectivity rather than the structure (connectome) itself as a
      biomarker of disease. Dynamic connectomes, in addition to currently used
      structural, functional, or effective connectivity, could be an important future
      biomarker for clinical applications. 

PMID- 23966937
TI  - Self-Associations Influence Task-Performance through Bayesian Inference.
AB  - The way we think about ourselves impacts greatly on our behavior. This paper
      describes a behavioral study and a computational model that shed new light on
      this important area. Participants were primed "clever" and "stupid" using a
      scrambled sentence task, and we measured the effect on response time and error
      rate on a rule-association task. First, we observed a confirmation bias effect in
      that associations to being "stupid" led to a gradual decrease in performance,
      whereas associations to being "clever" did not. Second, we observed that the
      activated self-concepts selectively modified attention toward one's performance.
      There was an early to late double dissociation in RTs in that primed "clever"
      resulted in RT increase following error responses, whereas primed "stupid"
      resulted in RT increase following correct responses. We propose a computational
      model of subjects' behavior based on the logic of the experimental task that
      involves two processes; memory for rules and the integration of rules with
      subsequent visual cues. The model incorporates an adaptive decision threshold
      based on Bayes rule, whereby decision thresholds are increased if integration was
      inferred to be faulty. Fitting the computational model to experimental data
      confirmed our hypothesis that priming affects the memory process. This model
      explains both the confirmation bias and double dissociation effects and
      demonstrates that Bayesian inferential principles can be used to study the effect
      of self-concepts on behavior. 

PMID- 23966936
TI  - What Can Psychiatric Disorders Tell Us about Neural Processing of the Self?
AB  - Many psychiatric disorders are associated with abnormal self-processing. While
      these disorders also have a wide-range of complex, and often heterogeneous sets
      of symptoms involving different cognitive, emotional, and motor domains, an
      impaired sense of self can contribute to many of these. Research investigating
      self-processing in healthy subjects has facilitated identification of changes in
      specific neural circuits which may cause altered self-processing in psychiatric
      disorders. While there is evidence for altered self-processing in many
      psychiatric disorders, here we will focus on four of the most studied ones,
      schizophrenia, autism spectrum disorder (ASD), major depression, and borderline
      personality disorder (BPD). We review evidence for dysfunction in two different
      neural systems implicated in self-processing, namely the cortical midline system
      (CMS) and the mirror neuron system (MNS), as well as contributions from altered
      inter-hemispheric connectivity (IHC). We conclude that while abnormalities in
      frontal-parietal activity and/or connectivity in the CMS are common to all four
      disorders there is more disruption of integration between frontal and parietal
      regions resulting in a shift toward parietal control in schizophrenia and ASD
      which may contribute to the greater severity and delusional aspects of their
      symptoms. Abnormalities in the MNS and in IHC are also particularly evident in
      schizophrenia and ASD and may lead to disturbances in sense of agency and the
      physical self in these two disorders. A better future understanding of how
      changes in the neural systems sub-serving self-processing contribute to different
      aspects of symptom abnormality in psychiatric disorders will require that more
      studies carry out detailed individual assessments of altered self-processing in
      conjunction with measurements of neural functioning. 

PMID- 23966938
TI  - Motor cortex neuroplasticity following brachial plexus transfer.
AB  - In the past decade, research has demonstrated that cortical plasticity, once
      thought only to exist in the early stages of life, does indeed continue on into
      adulthood. Brain plasticity is now acknowledged as a core principle of brain
      function and describes the ability of the central nervous system to adapt and
      modify its structural organization and function as an adaptive response to
      functional demand. In this clinical case study we describe how we used
      neuroimaging techniques to observe the functional topographical expansion of a
      patch of cortex along the sensorimotor cortex of a 27-year-old woman following
      brachial plexus transfer surgery to re-innervate her left arm. We found bilateral
      activations present in the thalamus, caudate, insula as well as across the
      sensorimotor cortex during an elbow flex motor task. In contrast we found less
      activity in the sensorimotor cortex for a finger tap motor task in addition to
      activations lateralized to the left inferior frontal gyrus and thalamus and
      bilaterally for the insula. From a pain perspective the patient who had
      experienced extensive phantom limb pain (PLP) before surgery found these
      sensations were markedly reduced following transfer of the right brachial plexus
      to the intact left arm. Within the context of this clinical case the results
      suggest that functional improvements in limb mobility are associated with
      increased activation in the sensorimotor cortex as well as reduced PLP. 

PMID- 23966939
TI  - Spatiotemporal characteristics of muscle patterns for ball catching.
AB  - What sources of information and what control strategies the central nervous
      system (CNS) uses to perform movements that require accurate sensorimotor
      coordination, such as catching a flying ball, is still debated. Here we analyzed
      the EMG waveforms recorded from 16 shoulder and elbow muscles in six subjects
      during catching of balls projected frontally from a distance of 6 m and arriving
      at two different heights and with three different flight times (550, 650, 750
      ms). We found that a large fraction of the variation in the muscle patterns was
      captured by two time-varying muscle synergies, coordinated recruitment of groups
      of muscles with specific activation waveforms, modulated in amplitude and shifted
      in time according to the ball's arrival height and flight duration. One synergy
      was recruited with a short and fixed delay from launch time. Remarkably, a second
      synergy was recruited at a fixed time before impact, suggesting that it is timed
      according to an accurate time-to-contact estimation. These results suggest that
      the control of interceptive movements relies on a combination of reactive and
      predictive processes through the intermittent recruitment of time-varying muscle
      synergies. Knowledge of the dynamic effect of gravity and drag on the ball may be
      then implicitly incorporated in a direct mapping of visual information into a
      small number of synergy recruitment parameters. 

PMID- 23966941
TI  - Is isoprenylcysteine carboxyl methyltransferase the key to reverse ageing?

PMID- 23966940
TI  - Direct connections assist neurons to detect correlation in small amplitude
      noises.
AB  - We address a question on the effect of common stochastic inputs on the
      correlation of the spike trains of two neurons when they are coupled through
      direct connections. We show that the change in the correlation of small amplitude
      stochastic inputs can be better detected when the neurons are connected by direct
      excitatory couplings. Depending on whether intrinsic firing rate of the neurons
      is identical or slightly different, symmetric or asymmetric connections can
      increase the sensitivity of the system to the input correlation by changing the
      mean slope of the correlation transfer function over a given range of input
      correlation. In either case, there is also an optimum value for synaptic strength
      which maximizes the sensitivity of the system to the changes in input
      correlation. 

PMID- 23966942
TI  - Amylin receptor: a common pathophysiological target in Alzheimer's disease and
      diabetes mellitus.
AB  - Amylin (islet amyloid polypeptide) and amyloid-beta (Abeta) protein, which are
      deposited within pancreatic islets of diabetics and brains of Alzheimer's
      patients respectively, share many biophysical and physiological properties.
      Emerging evidence indicates that the amylin receptor is a putative target
      receptor for the actions of human amylin and Abeta in the brain. The amylin
      receptor consists of the calcitonin receptor dimerized with a receptor activity
      modifying protein and is widely distributed within central nervous system. Both
      amylin and Abeta directly activate this G protein-coupled receptor and trigger
      multiple common intracellular signal transduction pathways that can culminate in
      apoptotic cell death. Moreover, amylin receptor antagonists can block both the
      biological and neurotoxic effects of human amylin and Abeta. Amylin receptors
      thus appear to be involved in the pathophysiology of Alzheimer's disease and
      diabetes, and could serve as a molecular link between the two conditions that are
      associated epidemiologically. 

PMID- 23966943
TI  - PIST (GOPC) modulates the oncogenic voltage-gated potassium channel KV10.1.
AB  - Although crucial for their correct function, the mechanisms controlling surface
      expression of ion channels are poorly understood. In the case of the voltage
      gated potassium channel KV10.1, this is determinant not only for its
      physiological function in brain, but also for its pathophysiology in tumors and
      possible use as a therapeutic target. The Golgi resident protein PIST binds
      several membrane proteins, thereby modulating their expression. Here we describe
      a PDZ domain-mediated interaction of KV10.1 and PIST, which enhances surface
      levels of KV10.1. The functional, but not the physical interaction of both
      proteins is dependent on the coiled-coil and PDZ domains of PIST; insertion of
      eight amino acids in the coiled-coil domain to render the neural form of PIST
      (nPIST) and the corresponding short isoform in an as-of-yet unknown form
      abolishes the effect. In addition, two new isoforms of PIST (sPIST and nsPIST)
      lacking nearly the complete PDZ domain were cloned and shown to be ubiquitously
      expressed. PIST and KV10.1 co-precipitate from native and expression systems.
      nPIST also showed interaction, but did not alter the functional expression of the
      channel. We could not document physical interaction between KV10.1 and sPIST, but
      it reduced KV10.1 functional expression in a dominant-negative manner. nsPIST
      showed weak physical interaction and no functional effect on KV10.1. We propose
      these isoforms to work as modulators of PIST function via regulating the binding
      on interaction partners. 

PMID- 23966945
TI  - Permeability of the peroxisomal membrane: lessons from the glyoxylate cycle.
AB  - Glyoxylate serves as intermediate in various metabolic pathways, although high
      concentrations of this metabolite are toxic to the cell. In many organisms
      glyoxylate is fed into the glyoxylate cycle. Enzymes participating in this
      metabolism are located on both sides of the peroxisomal membrane. The
      permeability of this membrane for small metabolites paves the way for exchange of
      intermediates between proteins catalyzing consecutive reactions. A model, in
      which soluble enzymes accumulate in close proximity to both ends of pore-like
      structures forming a transmembrane metabolon could explain the rapid and targeted
      exchange of intermediates. The metabolites passing the membrane differ between
      the three model organisms Saccharomyces cerevisiae, Arabidopsis thaliana, and
      Candida albicans, which reflects the ease of evolutionary adaptation processes
      whenever specific transporter proteins are not involved. The atypical
      permeability properties of the peroxisomal membrane together with a flexible
      structural arrangement ensuring the swift and selective transport across the
      membrane might represent the molecular basis for the functional versatility of
      peroxisomes. 

PMID- 23966944
TI  - Eat to reproduce: a key role for the insulin signaling pathway in adult insects.
AB  - Insects, like all heterotrophic organisms, acquire from their food the nutrients
      that are essential for anabolic processes that lead to growth (larval stages) or
      reproduction (adult stage). In adult females, this nutritional input is processed
      and results in a very specific output, i.e., the production of fully developed
      eggs ready for fertilization and deposition. An important role in this input
      output transition is attributed to the insulin signaling pathway (ISP). The ISP
      is considered to act as a sensor of the organism's nutritional status and to
      stimulate the progression of anabolic events when the status is positive. In
      several insect species belonging to different orders, the ISP has been
      demonstrated to positively control vitellogenesis and oocyte growth. Whether or
      not ISP acts herein via a mediator action of lipophilic insect hormones
      (ecdysteroids and juvenile hormone) remains debatable and might be differently
      controlled in different insect orders. Most likely, insulin-related peptides,
      ecdysteroids and juvenile hormone are involved in a complex regulatory network,
      in which they mutually influence each other and in which the insect's nutritional
      status is a crucial determinant of the network's output. The current review will
      present an overview of the regulatory role of the ISP in female insect
      reproduction and its interaction with other pathways involving nutrients,
      lipophilic hormones and neuropeptides. 

PMID- 23966946
TI  - Cellular and population plasticity of helper CD4(+) T cell responses.
AB  - Vertebrates are constantly exposed to pathogens, and the adaptive immunity has
      most likely evolved to control and clear such infectious agents. CD4(+) T cells
      are the major players in the adaptive immune response to pathogens. Following
      recognition of pathogen-derived antigens naive CD4(+) T cells differentiate into
      effectors which then control pathogen replication either directly by killing
      pathogen-infected cells or by assisting with generation of cytotoxic T
      lymphocytes (CTLs) or pathogen-specific antibodies. Pathogen-specific effector
      CD4(+) T cells are highly heterogeneous in terms of cytokines they produce. Three
      major subtypes of effector CD4(+) T cells have been identified: T-helper 1 (Th1)
      cells producing IFN-gamma and TNF-alpha, Th2 cells producing IL-4 and IL-10, and
      Th17 cells producing IL-17. How this heterogeneity is maintained and what
      regulates changes in effector T cell composition during chronic infections
      remains poorly understood. In this review we discuss recent advances in our
      understanding of CD4(+) T cell differentiation in response to microbial
      infections. We propose that a change in the phenotype of pathogen-specific
      effector CD4(+) T cells during chronic infections, for example, from Th1 to Th2
      response as observed in Mycobactrium avium ssp. paratuberculosis (MAP) infection
      of ruminants, can be achieved by conversion of T cells from one effector subset
      to another (cellular plasticity) or due to differences in kinetics
      (differentiation, proliferation, death) of different effector T cell subsets
      (population plasticity). We also shortly review mathematical models aimed at
      describing CD4(+) T cell differentiation and outline areas for future
      experimental and theoretical research. 

PMID- 23966947
TI  - Mitochondria: the cell powerhouse and nexus of stress.

PMID- 23966949
TI  - Social calls of flying big brown bats (Eptesicus fuscus).
AB  - Vocalizations serving a variety of social functions have been reported in many
      bat species (Order Chiroptera). While echolocation by big brown bats (Eptesicus
      fuscus) has been the subject of extensive study, calls used by this species for
      communication have received comparatively little research attention. Here, we
      report on a rich repertoire of vocalizations produced by big brown bats in a
      large flight room equipped with synchronized high speed stereo video and audio
      recording equipment. Bats were studied individually and in pairs, while sex, age,
      and experience with a novel foraging task were varied. We used discriminant
      function analysis (DFA) to classify six different vocalizations that were
      recorded when two bats were present. Contingency table analyses revealed a higher
      prevalence of social calls when males were present, and some call types varied in
      frequency of emission based on trial type or bat age. Bats flew closer together
      around the time some social calls were emitted, indicating that communicative
      calls may be selectively produced when conspecifics fly near one another. These
      findings are the first reports of social calls from flying big brown bats and
      provide insight into the function of communicative vocalizations emitted by this
      species. 

PMID- 23966950
TI  - Differential transport function of lymphatic vessels in the rat tail model and
      the long-term effects of Indocyanine Green as assessed with near-infrared
      imaging.
AB  - INTRODUCTION: Near-infrared (NIR) imaging has emerged as a novel imaging modality
      for assessing lymphatic function in vivo. While the technique has provided
      quantitative data previously unavailable, questions remain in regards to the
      spatiotemporal capabilities of the approach. We address three of the more
      important issues here using the rodent tail, one of the most widely utilized in
      vivo model systems in the lymphatic literature. Specifically we demonstrate (1)
      the transient vs. steady state response of lymphatics to tracer injection, (2)
      the functional characteristics of multiple collecting vessels draining the same
      tissue space in parallel, and (3) the long-term consequences of fluorescent
      tracers on lymphatic function to repeated functional measurements. METHODS: Rat
      tails were imaged with NIR and metrics of function were calculated for both
      collecting vessels that drain the tail. A nitric oxide donor cream (GTNO) was
      applied to the tail. Additionally, two different NIR dyes, indocyanine green
      (ICG) and LI-COR IRDye 800CW PEG, were utilized for function imaging at the time
      of initial injection and at 1, 2, and 4 week follow-up time points after which
      both draining lymph nodes were harvested. RESULTS AND DISCUSSION: Significant
      differences were found between the two collecting vessels such that the vessel
      first showing fluorescence (dominant) produced enhanced functional metrics
      compared to the second vessel (non-dominant). GTNO significantly reduced
      lymphatic function in the non-dominant vessel compared to the dominant. ICG
      remained visible in the tail for 2 weeks after injection and was accompanied by
      significant losses in lymphatic function and enlarged draining lymph nodes. The
      Licor tracer also remained visible for 2 weeks. However, the dye produced
      significantly lower effects on lymphatic function than ICG, and lymph nodes were
      not enlarged at any time point, suggesting that this may be a more appropriate
      contrast agent for longitudinal lymphatic imaging.

PMID- 23966948
TI  - Ionizing radiation, ion transports, and radioresistance of cancer cells.
AB  - The standard treatment of many tumor entities comprises fractionated radiation
      therapy which applies ionizing radiation to the tumor-bearing target volume.
      Ionizing radiation causes double-strand breaks in the DNA backbone that result in
      cell death if the number of DNA double-strand breaks exceeds the DNA repair
      capacity of the tumor cell. Ionizing radiation reportedly does not only act on
      the DNA in the nucleus but also on the plasma membrane. In particular, ionizing
      radiation-induced modifications of ion channels and transporters have been
      reported. Importantly, these altered transports seem to contribute to the
      survival of the irradiated tumor cells. The present review article summarizes our
      current knowledge on the underlying mechanisms and introduces strategies to
      radiosensitize tumor cells by targeting plasma membrane ion transports. 

PMID- 23966951
TI  - The relationship between P2X4 and P2X7: a physiologically important interaction?
AB  - Purinergic signaling within the kidney is becoming an important focus in the
      study of renal health and disease. The effectors of ATP signaling, the P2Y and
      P2X receptors, are expressed to varying extents in and along the nephron. There
      are many studies demonstrating the importance of the P2Y2 receptor on kidney
      function, and other P2 receptors are now emerging as participants in renal
      regulation. The P2X4 receptor has been linked to epithelial sodium transport in
      the nephron and expression levels of the P2X7 receptor are up-regulated in
      certain pathophysiological states. P2X7 antagonism has been shown to ameliorate
      rodent models of DOCA salt-induced hypertension and P2X4 null mice are
      hypertensive. Interestingly, polymorphisms in the genetic loci of P2X4 and P2X7
      have been linked to blood pressure variation in human studies. In addition to the
      increasing evidence linking these two P2X receptors to renal function and health,
      a number of studies link the two receptors in terms of physical associations
      between their subunits, demonstrated both in vitro and in vivo. This review will
      analyze the current literature regarding interactions between P2X4 and P2X7 and
      assess the potential impact of these with respect to renal function. 

PMID- 23966952
TI  - Insulin-like and IGF-like peptides in the silkmoth Bombyx mori: discovery,
      structure, secretion, and function.
AB  - A quarter of a century has passed since bombyxin, the first insulin-like peptide
      identified in insects, was discovered in the silkmoth Bombyx mori. During these
      years, bombyxin has been studied for its structure, genes, distribution,
      hemolymph titers, secretion control, as well as physiological functions, thereby
      stimulating a wide range of studies on insulin-like peptides in other insects.
      Moreover, recent studies have identified a new class of insulin family peptides,
      IGF-like peptides, in B. mori and Drosophila melanogaster, broadening the base of
      the research area of the insulin-related peptides in insects. In this review, we
      describe the achievements of the studies on insulin-like and IGF-like peptides
      mainly in B. mori with short histories of their discovery. Our emphasis is that
      bombyxins, secreted by the brain neurosecretory cells, regulate nutrient
      dependent growth and metabolism, whereas the IGF-like peptides, secreted by the
      fat body and other peripheral tissues, regulate stage-dependent growth of
      tissues. 

PMID- 23966954
TI  - Intertemporal bargaining in addiction.
AB  - The debate between disease models of addiction and moral or voluntarist models
      has been endless, and often echoes the equally endless debate between determinism
      and free will. I suggest here that part of the problem comes from how we picture
      the function of motivation in self-control. Quantitative experiments in both
      humans and non-humans have shown that delayed reward loses its effectiveness in
      proportion to its delay. The resulting instability of preference is best
      controlled by a recursive self-prediction process, intertemporal bargaining,
      which is the likely mechanism of both the strength and the experienced freedom of
      will. In this model determinism is consistent with more elements of free will
      than compatibilist philosophers have heretofore proposed, and personal
      responsibility is an inseparable, functional component of will. Judgments of
      social responsibility can be described as projections of personal responsibility,
      but normative responsibility in addiction is elusive. The cited publications that
      are under the author's control can be downloaded from www.picoeconomics.org. 

PMID- 23966953
TI  - Role of extracellular ATP and P2 receptor signaling in regulating renal cyst
      growth and interstitial inflammation in polycystic kidney disease.
AB  - Polycystic kidney diseases (PKD) are a group of inherited ciliopathies in which
      the formation and growth of multiple cysts derived from the distal nephron and
      collecting duct leads to the disruption of normal kidney architecture, chronic
      interstitial inflammation/fibrosis and hypertension. Kidney failure is the most
      life-threatening complication of PKD, and is the consequence of cyst expansion,
      renal interstitial disease and loss of normal kidney tissue. Over the last
      decade, accumulating evidence suggests that the autocrine and paracrine effects
      of ATP (through its receptor family P2X and P2Y), could be detrimental for the
      progression of PKD. (2009). In vitro, ATP-P2 signaling promotes cystic epithelial
      cell proliferation, chloride-driven fluid secretion and apoptosis. Furthermore,
      dysfunction of the polycystin signal transduction pathways promotes the
      secretagogue activity of extracellular ATP by activating a calcium-activated
      chloride channel via purinergic receptors. Finally, ATP is a danger signal and
      could potentially contribute to interstitial inflammation associated with PKD.
      These data suggest that ATP-P2 signaling worsens the progression of cyst
      enlargement and interstitial inflammation in PKD. 

PMID- 23966955
TI  - Addiction: choice or compulsion?
AB  - Normative thinking about addiction has traditionally been divided between, on the
      one hand, a medical model which sees addiction as a disease characterized by
      compulsive and relapsing drug use over which the addict has little or no control
      and, on the other, a moral model which sees addiction as a choice characterized
      by voluntary behavior under the control of the addict. Proponents of the former
      appeal to evidence showing that regular consumption of drugs causes persistent
      changes in the brain structures and functions known to be involved in the
      motivation of behavior. On this evidence, it is often concluded that becoming
      addicted involves a transition from voluntary, chosen drug use to non-voluntary
      compulsive drug use. Against this view, proponents of the moral model provide
      ample evidence that addictive drug use involves voluntary chosen behavior. In
      this article we argue that although they are right about something, both views
      are mistaken. We present a third model that neither rules out the view of
      addictive drug use as compulsive, nor that it involves voluntary chosen behavior.

PMID- 23966956
TI  - Polysubstance use in cannabis users referred for treatment: drug use profiles,
      psychiatric comorbidity and cannabis-related beliefs.
AB  - BACKGROUND: Population-based surveys demonstrate cannabis users are more likely
      to use both illicit and licit substances, compared with non-cannabis users. Few
      studies have examined the substance use profiles of cannabis users referred for
      treatment. Co-existing mental health symptoms and underlying cannabis-related
      beliefs associated with these profiles remains unexplored. METHODS: Comprehensive
      drug use and dependence severity (Severity of Dependence Scale-Cannabis) data
      were collected on a sample of 826 cannabis users referred for treatment. Patients
      completed the General Health Questionnaire, Cannabis Expectancy Questionnaire,
      Cannabis Refusal Self-Efficacy Questionnaire, and Positive Symptoms and Manic
      Excitement subscales of the Brief Psychiatric Rating Scale. Latent class analysis
      was performed on last month use of drugs to identify patterns of multiple drug
      use. Mental health comorbidity and cannabis beliefs were examined by identified
      drug use pattern. RESULTS: A three-class solution provided the best fit to the
      data: (1) cannabis and tobacco users (n = 176), (2) cannabis, tobacco, and
      alcohol users (n = 498), and (3) wide-ranging substance users (n = 132). Wide
      ranging substance users (3) reported higher levels of cannabis dependence
      severity, negative cannabis expectancies, lower opportunistic, and emotional
      relief self-efficacy, higher levels of depression and anxiety and higher manic
      excitement and positive psychotic symptoms. CONCLUSION: In a sample of cannabis
      users referred for treatment, wide-ranging substance use was associated with
      elevated risk on measures of cannabis dependence, co-morbid psychopathology, and
      dysfunctional cannabis cognitions. These findings have implications for cognitive
      behavioral assessment and treatment.

PMID- 23966958
TI  - A cross-sectional analysis of the development of response inhibition in children
      with chromosome 22q11.2 deletion syndrome.
AB  - Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder that
      is associated with cognitive impairments and significantly elevated risk for
      developing schizophrenia. While impairments in response inhibition are central to
      executive dysfunction in schizophrenia, the nature and development of such
      impairments in children with 22q11.2DS, a group at high risk for the disorder,
      are not clear. Here we used a classic Go/No-Go paradigm to quantify proactive
      (anticipatory stopping) and reactive (actual stopping) response inhibition in 47
      children with 22q11.2DS and 36 typically developing (TD) children, all ages 7-14.
      A cross-sectional design was used to examine age-related associations with
      response inhibition. When compared with TD individuals, children with 22q11.2DS
      demonstrated typical proactive response inhibition at all ages. By contrast,
      reactive response inhibition was impaired in children with 22q11.2DS relative to
      TD children. While older age predicted better reactive response inhibition in TD
      children, there was no age-related association with reactive response inhibition
      in children with 22q11.2DS. Closer examination of individual performance data
      revealed a wide range of performance abilities in older children with 22q11.2DS;
      some typical and others highly impaired. The results of this cross-sectional
      analysis suggest an impaired developmental trajectory of reactive response
      inhibition in some children with 22q11.2DS that might be related to atypical
      development of neuroanatomical systems underlying this cognitive process. As part
      of a larger study, this investigation might help identify risk factors for
      conversion to schizophrenia and lead to early diagnosis and preventive
      intervention. 

PMID- 23966957
TI  - Epigenetic Risk Factors in PTSD and Depression.
AB  - Epidemiological and clinical studies have shown that children exposed to adverse
      experiences are at increased risk for the development of depression, anxiety
      disorders, and posttraumatic stress disorder (PTSD). A history of child abuse and
      maltreatment increases the likelihood of being subsequently exposed to traumatic
      events or of developing PTSD as an adult. The brain is highly plastic during
      early life and encodes acquired information into lasting memories that normally
      subserve adaptation. Translational studies in rodents showed that enduring
      sensitization of neuronal and neuroendocrine circuits in response to early life
      adversity are likely risk factors of life time vulnerability to stress. Hereby,
      the hypothalamic-pituitary-adrenal (HPA) axis integrates cognitive, behavioral,
      and emotional responses to early-life stress and can be epigenetically programed
      during sensitive windows of development. Epigenetic mechanisms, comprising
      reciprocal regulation of chromatin structure and DNA methylation, are important
      to establish and maintain sustained, yet potentially reversible, changes in gene
      transcription. The relevance of these findings for the development of PTSD
      requires further studies in humans where experience-dependent epigenetic
      programing can additionally depend on genetic variation in the underlying
      substrates which may protect from or advance disease development. Overall,
      identification of early-life stress-associated epigenetic risk markers informing
      on previous stress history can help to advance early diagnosis, personalized
      prevention, and timely therapeutic interventions, thus reducing long-term social
      and health costs. 

PMID- 23966959
TI  - How Does a Neuron "know" to Modulate Its Epigenetic Machinery in Response to
      Early-Life Environment/Experience?
AB  - Exciting information is emerging about epigenetic mechanisms and their role in
      long-lasting changes of neuronal gene expression. Whereas these mechanisms are
      active throughout life, recent findings point to a critical window of early
      postnatal development during which neuronal gene expression may be persistently
      "re-programed" via epigenetic modifications. However, it remains unclear how the
      epigenetic machinery is modulated. Here we focus on an important example of early
      life programing: the effect of sensory input from the mother on expression
      patterns of key stress-related genes in the developing brain. We focus on the
      lasting effects of this early-life experience on corticotropin-releasing hormone
      (CRH) gene expression in the hypothalamus, and describe recent work that
      integrates organism-wide signals with cellular signals that in turn impact
      epigenetic regulation. We describe the operational brain networks that convey
      sensory input to CRH-expressing cells, and highlight the resulting "re-wiring" of
      synaptic connectivity to these neurons. We then move from intercellular to
      intracellular mechanisms, speculating about the induction, and maintenance of
      lifelong CRH repression provoked by early-life experience. Elucidating such
      pathways is critical for understanding the enduring links between experience and
      gene expression. In the context of responses to stress, such mechanisms should
      contribute to vulnerability or resilience to post-traumatic stress disorder
      (PTSD) and other stress-related disorders. 

PMID- 23966960
TI  - Alpha reactivity to first names differs in subjects with high and low dream
      recall frequency.
AB  - Studies in cognitive psychology showed that personality (openness to experience,
      thin boundaries, absorption), creativity, nocturnal awakenings, and attitude
      toward dreams are significantly related to dream recall frequency (DRF). These
      results suggest the possibility of neurophysiological trait differences between
      subjects with high and low DRF. To test this hypothesis we compared sleep
      characteristics and alpha reactivity to sounds in subjects with high and low DRF
      using polysomnographic recordings and electroencephalography (EEG). We acquired
      EEG from 21 channels in 36 healthy subjects while they were presented with a
      passive auditory oddball paradigm (frequent standard tones, rare deviant tones
      and very rare first names) during wakefulness and sleep (intensity, 50 dB above
      the subject's hearing level). Subjects were selected as High-recallers (HR, DRF =
      4.42 +/- 0.25 SEM, dream recalls per week) and Low-recallers (LR, DRF = 0.25 +/-
      0.02) using a questionnaire and an interview on sleep and dream habits. Despite
      the disturbing setup, the subjects' quality of sleep was generally preserved.
      First names induced a more sustained decrease in alpha activity in HR than in LR
      at Pz (1000-1200 ms) during wakefulness, but no group difference was found in REM
      sleep. The current dominant hypothesis proposes that alpha rhythms would be
      involved in the active inhibition of the brain regions not involved in the
      ongoing brain operation. According to this hypothesis, a more sustained alpha
      decrease in HR would reflect a longer release of inhibition, suggesting a deeper
      processing of complex sounds than in LR during wakefulness. A possibility to
      explain the absence of group difference during sleep is that increase in alpha
      power in HR may have resulted in awakenings. Our results support this hypothesis
      since HR experienced more intra sleep wakefulness than LR (30 +/- 4 vs. 14 +/- 4
      min). As a whole our results support the hypothesis of neurophysiological trait
      differences in high and low-recallers. 

PMID- 23966961
TI  - Not all minds that wander are lost: the importance of a balanced perspective on
      the mind-wandering state.
AB  - The waking mind is often occupied with mental contents that are minimally
      constrained by events in the here and now. These self-generated thoughts-e.g.,
      mind-wandering or daydreaming-interfere with external task performance and can be
      a marker for unhappiness and even psychiatric problems. They also occupy our
      thoughts for upwards of half of the time, and under non-demanding conditions they
      (i) allow us to connect our past and future selves together, (ii) help us make
      successful long-term plans and (iii) can provide a source of creative
      inspiration. The lengths that the mind goes to self-generate thought, coupled
      with its apparent functionality, suggest that the mind places a higher priority
      on such cognition than on many other mental acts. Although mind-wandering may be
      unpleasant for the individual who experiences it and disruptive to the tasks of
      the moment, self-generated thought allows consciousness freedom from the here and
      now and so reflects a key evolutionary adaptation for the mind. Here we
      synthesize recent literature from cognitive and clinical psychology and propose
      two formal hypotheses that (1) highlight task context and thought content as
      critical factors that constrain the costs and benefits of self-generated thought
      and (2) provide direction on ways to investigate the costs and benefits from an
      impartial perspective. 

PMID- 23966962
TI  - Newborn infants' auditory system is sensitive to Western music chord categories.
AB  - Neural encoding of abstract rules in the audition of newborn infants has been
      recently demonstrated in several studies using event-related potentials (ERPs).
      In the present study the neural encoding of Western music chords was investigated
      in newborn infants. Using ERPs, we examined whether the categorizations of major
      vs. minor and consonance vs. dissonance are present at the level of the change
      related mismatch response (MMR). Using an oddball paradigm, root minor, dissonant
      and inverted major chords were presented in a context of consonant root major
      chords. The chords were transposed to several different frequency levels, so that
      the deviant chords did not include a physically deviant frequency that could
      result in an MMR without categorization. The results show that the newborn
      infants were sensitive to both dissonant and minor chords but not to inverted
      major chords in the context of consonant root major chords. While the dissonant
      chords elicited a large positive MMR, the minor chords elicited a negative MMR.
      This indicates that the two categories were processed differently. The results
      suggest newborn infants are sensitive to Western music categorizations, which is
      consistent with the authors' previous studies in adults and school-aged children.

PMID- 23966964
TI  - Pros and cons of a wandering mind: a prospective study.
AB  - Mind wandering (MW) has recently been associated with both adaptive (e.g.,
      creativity enhancement) and maladaptive (e.g., mood worsening) consequences. This
      study aimed at investigating whether proneness to MW was prospectively associated
      with negative health outcomes. At time 0, 21 women, 19 men; mean age = 24.5 (4.9)
      underwent a 5-min baseline electrocardiogram (ECG), a 20-min laboratory tracking
      task with thought probes, and personality questionnaires. At time 1 (1 year
      follow-up), the same participants underwent a 24-h Ecological Momentary
      Assessment characterized by ambulatory ECG recording and electronic diaries.
      First, we examined if the likelihood of being a "mind wanderer" was associated
      with specific personality dispositions. Then, we tested if the occurrence of
      episodes of MW in the lab would be correlated with frequency of MW in daily life.
      Finally, multiple regression models were used to test if MW longitudinally acted
      as a risk factor for health, accounting for the effects of biobehavioral
      variables. Among dispositional traits, the frequency of MW episodes in daily life
      was inversely associated with the capacity of being mindful (i.e., aware of the
      present moment and non-judging). There was a positive correlation between
      frequency of MW in the lab and in daily life, suggesting that it is a stable
      disposition of the individual. When differentiated from perseverative cognition
      (i.e., rumination and worry), MW did not predict the presence of health risk
      factors 1 year later, however, a higher occurrence of episodes of MW was
      associated with short-term adverse consequences, such as increased 24-h heart
      rate (HR) on the same day and difficulty falling asleep the subsequent night.
      Present findings suggest that MW may be associated with short term "side effects"
      but argue against a long term dysfunctional view of this cognitive process. 

PMID- 23966963
TI  - Toward a unified model of face and object recognition in the human visual system.
AB  - Our understanding of the mechanisms and neural substrates underlying visual
      recognition has made considerable progress over the past 30 years. During this
      period, accumulating evidence has led many scientists to conclude that objects
      and faces are recognised in fundamentally distinct ways, and in fundamentally
      distinct cortical areas. In the psychological literature, in particular, this
      dissociation has led to a palpable disconnect between theories of how we process
      and represent the two classes of object. This paper follows a trend in part of
      the recognition literature to try to reconcile what we know about these two forms
      of recognition by considering the effects of learning. Taking a widely accepted,
      self-organizing model of object recognition, this paper explains how such a
      system is affected by repeated exposure to specific stimulus classes. In so
      doing, it explains how many aspects of recognition generally regarded as unusual
      to faces (holistic processing, configural processing, sensitivity to inversion,
      the other-race effect, the prototype effect, etc.) are emergent properties of
      category-specific learning within such a system. Overall, the paper describes how
      a single model of recognition learning can and does produce the seemingly very
      different types of representation associated with faces and objects. 

PMID- 23966965
TI  - (A)musicality in Williams syndrome: examining relationships among auditory
      perception, musical skill, and emotional responsiveness to music.
AB  - Williams syndrome (WS), a genetic, neurodevelopmental disorder, is of keen
      interest to music cognition researchers because of its characteristic auditory
      sensitivities and emotional responsiveness to music. However, actual musical
      perception and production abilities are more variable. We examined musicality in
      WS through the lens of amusia and explored how their musical perception abilities
      related to their auditory sensitivities, musical production skills, and emotional
      responsiveness to music. In our sample of 73 adolescents and adults with WS, 11%
      met criteria for amusia, which is higher than the 4% prevalence rate reported in
      the typically developing (TD) population. Amusia was not related to auditory
      sensitivities but was related to musical training. Performance on the amusia
      measure strongly predicted musical skill but not emotional responsiveness to
      music, which was better predicted by general auditory sensitivities. This study
      represents the first time amusia has been examined in a population with a known
      neurodevelopmental genetic disorder with a range of cognitive abilities. Results
      have implications for the relationships across different levels of auditory
      processing, musical skill development, and emotional responsiveness to music, as
      well as the understanding of gene-brain-behavior relationships in individuals
      with WS and TD individuals with and without amusia. 

PMID- 23966966
TI  - Attentional capture by social stimuli in young infants.
AB  - We investigated the possibility that a range of social stimuli capture the
      attention of 6-month-old infants when in competition with other non-face objects.
      Infants viewed a series of six-item arrays in which one target item was a face,
      body part, or animal as their eye movements were recorded. Stimulus arrays were
      also processed for relative salience of each item in terms of color, luminance,
      and amount of contour. Targets were rarely the most visually salient items in the
      arrays, yet infants' first looks toward all three target types were above chance,
      and dwell times for targets exceeded other stimulus types. Girls looked longer at
      faces than did boys, but there were no sex differences for other stimuli. These
      results are interpreted in a context of learning to discriminate between
      different classes of animate stimuli, perhaps in line with affordances for social
      interaction, and origins of sex differences in social attention. 

PMID- 23966967
TI  - An amodal shared resource model of language-mediated visual attention.
AB  - Language-mediated visual attention describes the interaction of two fundamental
      components of the human cognitive system, language and vision. Within this paper
      we present an amodal shared resource model of language-mediated visual attention
      that offers a description of the information and processes involved in this
      complex multimodal behavior and a potential explanation for how this ability is
      acquired. We demonstrate that the model is not only sufficient to account for the
      experimental effects of Visual World Paradigm studies but also that these effects
      are emergent properties of the architecture of the model itself, rather than
      requiring separate information processing channels or modular processing systems.
      The model provides an explicit description of the connection between the modality
      specific input from language and vision and the distribution of eye gaze in
      language-mediated visual attention. The paper concludes by discussing future
      applications for the model, specifically its potential for investigating the
      factors driving observed individual differences in language-mediated eye gaze. 

PMID- 23966968
TI  - How can audiovisual pathways enhance the temporal resolution of time-compressed
      speech in blind subjects?
AB  - In blind people, the visual channel cannot assist face-to-face communication via
      lipreading or visual prosody. Nevertheless, the visual system may enhance the
      evaluation of auditory information due to its cross-links to (1) the auditory
      system, (2) supramodal representations, and (3) frontal action-related areas.
      Apart from feedback or top-down support of, for example, the processing of
      spatial or phonological representations, experimental data have shown that the
      visual system can impact auditory perception at more basic computational stages
      such as temporal signal resolution. For example, blind as compared to sighted
      subjects are more resistant against backward masking, and this ability appears to
      be associated with activity in visual cortex. Regarding the comprehension of
      continuous speech, blind subjects can learn to use accelerated text-to-speech
      systems for "reading" texts at ultra-fast speaking rates (>16 syllables/s),
      exceeding by far the normal range of 6 syllables/s. A functional magnetic
      resonance imaging study has shown that this ability, among other brain regions,
      significantly covaries with BOLD responses in bilateral pulvinar, right visual
      cortex, and left supplementary motor area. Furthermore, magnetoencephalographic
      measurements revealed a particular component in right occipital cortex phase
      locked to the syllable onsets of accelerated speech. In sighted people, the
      "bottleneck" for understanding time-compressed speech seems related to higher
      demands for buffering phonological material and is, presumably, linked to frontal
      brain structures. On the other hand, the neurophysiological correlates of
      functions overcoming this bottleneck, seem to depend upon early visual cortex
      activity. The present Hypothesis and Theory paper outlines a model that aims at
      binding these data together, based on early cross-modal pathways that are already
      known from various audiovisual experiments on cross-modal adjustments during
      space, time, and object recognition. 

PMID- 23966969
TI  - Count on dopamine: influences of COMT polymorphisms on numerical cognition.
AB  - Catechol-O-methyltransferase (COMT) is an enzyme that is particularly important
      for the metabolism of dopamine. Functional polymorphisms of COMT have been
      implicated in working memory and numerical cognition. This is an exploratory
      study that aims at investigating associations between COMT polymorphisms, working
      memory, and numerical cognition. Elementary school children from 2th to 6th
      grades were divided into two groups according to their COMT val158met
      polymorphism [homozygous for valine allele (n = 61) vs. heterozygous plus
      methionine homozygous children or met+ group (n = 94)]. Both groups were matched
      for age and intelligence. Working memory was assessed through digit span and
      Corsi blocks. Symbolic numerical processing was assessed through transcoding and
      single-digit word problem tasks. Non-symbolic magnitude comparison and estimation
      tasks were used to assess number sense. Between-group differences were found in
      symbolic and non-symbolic numerical tasks, but not in working memory tasks.
      Children in the met+ group showed better performance in all numerical tasks while
      val homozygous children presented slower development of non-symbolic magnitude
      representations. These results suggest COMT-related dopaminergic modulation may
      be related not only to working memory, as found in previous studies, but also to
      the development of magnitude processing and magnitude representations. 

PMID- 23966970
TI  - Oxytocin and social pretreatment have similar effects on processing of negative
      emotional faces in healthy adult males.
AB  - Oxytocin has been shown to affect several aspects of human social cognition,
      including facial emotion processing. There is also evidence that social stimuli
      (such as eye-contact) can effectively modulate endogenous oxytocin levels. In the
      present study we directly tested whether intranasal oxytocin administration and
      pre-treatment with social stimuli had similar effects on face processing at the
      behavioral level. Subjects (N = 52 healthy adult males) were presented with a set
      of faces with expressions of different valence (negative, neutral, positive)
      following different types of pretreatment (oxytocin-OT or placebo-PL and social
      interaction-Soc or no social interaction-NSoc, N = 13 in each) and were asked to
      rate all faces for perceived emotion and trustworthiness. On the next day
      subjects' recognition memory was tested on a set of neutral faces and
      additionally they had to again rate each face for trustworthiness and emotion.
      Subjects in both the OT and the Soc pretreatment group (as compared to the PL and
      to the NSoc groups) gave higher emotion and trustworthiness scores for faces with
      negative emotional expression. Moreover, 24 h later, subjects in the OT and Soc
      groups (unlike in control groups) gave lower trustworthiness scores for
      previously negative faces, than for faces previously seen as emotionally neutral
      or positive. In sum these results provide the first direct evidence of the
      similar effects of intranasal oxytocin administration and social stimulation on
      the perception of negative facial emotions as well as on the delayed recall of
      negative emotional information. 

PMID- 23966971
TI  - Prolonged disengagement from distractors near the hands.
AB  - Because items near our hands are often more important than items far from our
      hands, the brain processes visual items near our hands differently than items far
      from our hands. Multiple experiments have attributed this processing difference
      to spatial attention, but the exact mechanism behind how spatial attention near
      our hands changes is still under investigation. The current experiments sought to
      differentiate between two of the proposed mechanisms: a prioritization of the
      space near the hands and a prolonged disengagement of spatial attention near the
      hands. To differentiate between these two accounts, we used the additional
      singleton paradigm in which observers searched for a shape singleton among
      homogenously shaped distractors. On half the trials, one of the distractors was a
      different color. Both the prioritization and disengagement accounts predict
      differently colored distractors near the hands will slow target responses more
      than differently colored distractors far from the hands, but the prioritization
      account also predicts faster responses to targets near the hands than far from
      the hands. The disengagement account does not make this prediction, because
      attention does not need to be disengaged when the target appears near the hand.
      We found support for the disengagement account: Salient distractors near the
      hands slowed responses more than those far from the hands, yet observers did not
      respond faster to targets near the hands. 

PMID- 23966972
TI  - Is there a role for treating inflammation in moyamoya disease?: a review of
      histopathology, genetics, and signaling cascades.
AB  - Moyamoya disease is a slowly progressing steno-occlusive condition affecting the
      cerebrovasculature. Affecting the terminal internal carotid arteries (ICA) and
      there branches, bilaterally, a resulting in a fine vascular network in the base
      of the brain to allow for compensation of the stenosed vessels. While there is
      obvious evidence of the involvement of inflammatory proteins in the condition,
      this has historically not been acknowledged as a causal factor. Here we describe
      the fundamental histopathology, genetics, and signaling cascades involved in
      moyamoya and debate whether these factors can be linked as causal factor for the
      condition or whether they are simply a secondary result of the ischemia described
      in the condition. A particular focus has been placed on the multitude of
      signaling cascades linked to the condition as these are viewed as having the
      greatest therapeutic potential. As such we hope to draw some novel insight into
      potential diagnostic and therapeutic inflammatory targets in the condition. 

PMID- 23966974
TI  - Nonlinear variability of body sway in patients with phobic postural vertigo.
AB  - BACKGROUND: Subjective postural imbalance is a key symptom in the somatoform
      phobic postural vertigo (PPV). It has been assumed that more attentional control
      of body posture and / or co-contraction of leg muscles during standing is used to
      minimize the physiological body sway in PPV. Here we analyze nonlinear
      variability of body sway in patients with PPV in order to disclose changes in
      postural control strategy associated with PPV. METHODS: Twenty patients with PPV
      and 20 age-matched healthy subjects (HS) were recorded on a stabilometer platform
      with eyes open (EO), eyes closed (EC), and while standing on a foam rubber with
      eyes closed (ECF). Spatio-temporal changes of the center of pressure (CoP)
      displacement were analyzed to assess the structure of postural variability by
      computing the scaling exponent alpha and the sample entropy (SEn) of the time
      series. RESULTS: With EO on firm ground alpha and SEn of CoP displacement were
      significantly lower in patients (p < 0.001). For more difficult conditions (EC,
      ECF) postural variability in PPV assimilated to that of HS. CONCLUSION: Postural
      control in PPV patients differs from HS under normal stance condition. It is
      characterized by a reduced scaling behavior and higher regularity. These changes
      in the structure of postural variability might suggest an inappropriate
      attentional involvement with stabilizing strategies, which are used by HS only
      for more demanding balance tasks.

PMID- 23966975
TI  - In vivo Photometry during Movement Changes Our Understanding of the Direct and
      Indirect Pathways.

PMID- 23966973
TI  - Hyperphosphorylation-induced tau oligomers.
AB  - In normal adult brain the microtubule associated protein (MAP) tau contains 2-3
      phosphates per mol of the protein and at this level of phosphorylation it is a
      soluble cytosolic protein. The normal brain tau interacts with tubulin and
      promotes its assembly into microtubules and stabilizes these fibrils. In
      Alzheimer disease (AD) brain tau is three to fourfold hyperphosphorylated. The
      abnormally hyperphosphorylated tau binds to normal tau instead of the tubulin and
      this binding leads to the formation of tau oligomers. The tau oligomers can be
      sedimented at 200,000 * g whereas the normal tau under these conditions remains
      in the supernatant. The abnormally hyperphosphorylated tau is capable of
      sequestering not only normal tau but also MAP MAP1 and MAP2 and causing
      disruption of the microtubule network promoted by these proteins. Unlike Abeta
      and prion protein (PrP) oligomers, tau oligomerization in AD and related
      tauopathies is hyperphosphorylation-dependent; in vitro dephosphorylation of AD P
      tau with protein phosphatase 2A (PP2A) inhibits and rehyperphosphorylation of the
      PP2A-AD P-tau with more than one combination of tau protein kinases promotes its
      oligomerization. In physiological assembly conditions the AD P-tau readily self
      assembles into paired helical filaments. Missense tau mutations found in
      frontotemporal dementia apparently lead to tau oligomerization and
      neurofibrillary pathology by promoting its abnormal hyperphosphorylation.
      Dysregulation of the alternative splicing of tau that alters the 1:1 ratio of the
      3-repeat: 4-repeat taus such as in Down syndrome, Pick disease, and progressive
      supranuclear palsy leads to the abnormal hyperphosphorylation of tau. 

PMID- 23966976
TI  - The Differences between Blast-Induced and Sports-Related Brain Injuries.

PMID- 23966977
TI  - Efficacy and tolerability of intravenous levetiracetam in childrens.
AB  - Intractable epilepsy in children poses a serious medical challenge. Acute
      repetitive seizures and status epilepticus leads to frequent emergency room
      visits and hospital admissions. Delay of treatment may lead to resistance to the
      first-line anticonvulsant therapies. It has been shown that these children
      continue to remain intractable even after acute seizure management with approved
      Food and Drug Administration (FDA) agents. Intravenous levetiracetam, a second
      generation anticonvulsant was approved by the FDA in 2006 in patients 16 years
      and older as an alternative when oral treatment is not an option. Data have been
      published showing that intravenous levetiracetam is safe and efficacious, and can
      be used in an acute inpatient setting. This current review will discuss the
      recent data about the safety and tolerability of intravenous levetiracetam in
      children and neonates, and emphasize the need for a larger prospective
      multicenter trial to prove the efficacy of this agent in acute seizure
      management. 

PMID- 23966978
TI  - Shift work and circadian dysregulation of reproduction.
AB  - Health impairments, including reproductive issues, are associated with working
      nights or rotating shifts. For example, shift work has been associated with an
      increased risk of irregular menstrual cycles, endometriosis, infertility,
      miscarriage, low birth weight or pre-term delivery, and reduced incidence of
      breastfeeding. Based on what is known about circadian regulation of endocrine
      rhythms in rodents (and much less in humans), the circadian clock is an integral
      regulatory part of the reproductive system. When this 24-h program is disordered
      by environmental perturbation (such as shift work) or genetic alterations, the
      endocrine system can be impaired. The purpose of this review is to explore the
      hypothesis that misalignment of reproductive hormones with the environmental
      light-dark cycle and/or sleep-wake rhythms can disrupt menstrual cycles,
      pregnancy, and parturition. We highlight the role of the circadian clock in
      regulating human reproductive physiology and shift work-induced pathology within
      each step of the reproductive axis while exploring potential mechanisms from the
      animal model literature. In addition to documenting the reproductive hazards of
      shift work, we also point out important gaps in our knowledge as critical areas
      for future investigation. For example, future studies should examine whether
      forced desynchronization disrupts gonadotropin secretion rhythms and whether
      there are sleep/wake schedules that are better or worse for the adaptation of the
      reproductive system to shift work. These studies are necessary in order to define
      not only whether or not shift work-induced circadian misalignment impairs
      reproductive capacity, but also to identify strategies for the future that can
      minimize this desynchronization. 

PMID- 23966979
TI  - GPCR Heterodimerization in the Reproductive System: Functional Regulation and
      Implication for Biodiversity.
AB  - A G protein-coupled receptor (GPCR) functions not only as a monomer or homodimer
      but also as a heterodimer with another GPCR. GPCR heterodimerization results in
      the modulation of the molecular functions of the GPCR protomer, including ligand
      binding affinity, signal transduction, and internalization. There has been a
      growing body of reports on heterodimerization of multiple GPCRs expressed in the
      reproductive system and the resultant functional modulation, suggesting that GPCR
      heterodimerization is closely associated with reproduction including the
      secretion of hormones and the growth and maturation of follicles and oocytes.
      Moreover, studies on heterodimerization among paralogs of gonadotropin-releasing
      hormone (GnRH) receptors of a protochordate, Ciona intestinalis, verified the
      species-specific regulation of the functions of GPCRs via multiple GnRH receptor
      pairs. These findings indicate that GPCR heterodimerization is also involved in
      creating biodiversity. In this review, we provide basic and current knowledge
      regarding GPCR heterodimers and their functional modulation, and explore the
      biological significance of GPCR heterodimerization. 

PMID- 23966981
TI  - Astrocytic Control of Biosynthesis and Turnover of the Neurotransmitters
      Glutamate and GABA.
AB  - Glutamate and GABA are the quantitatively major neurotransmitters in the brain
      mediating excitatory and inhibitory signaling, respectively. These amino acids
      are metabolically interrelated and at the same time they are tightly coupled to
      the intermediary metabolism including energy homeostasis. Astrocytes play a
      pivotal role in the maintenance of the neurotransmitter pools of glutamate and
      GABA since only these cells express pyruvate carboxylase, the enzyme required for
      de novo synthesis of the two amino acids. Such de novo synthesis is obligatory to
      compensate for catabolism of glutamate and GABA related to oxidative metabolism
      when the amino acids are used as energy substrates. This, in turn, is influenced
      by the extent to which the cycling of the amino acids between neurons and
      astrocytes may occur. This cycling is brought about by the glutamate/GABA -
      glutamine cycle the operation of which involves the enzymes glutamine synthetase
      (GS) and phosphate-activated glutaminase together with the plasma membrane
      transporters for glutamate, GABA, and glutamine. The distribution of these
      proteins between neurons and astrocytes determines the efficacy of the cycle and
      it is of particular importance that GS is exclusively expressed in astrocytes. It
      should be kept in mind that the operation of the cycle is associated with
      movement of ammonia nitrogen between the two cell types and different mechanisms
      which can mediate this have been proposed. This review is intended to delineate
      the above mentioned processes and to discuss quantitatively their relative
      importance in the homeostatic mechanisms responsible for the maintenance of
      optimal conditions for the respective neurotransmission processes to operate. 

PMID- 23966980
TI  - Role of adaptor proteins in secretory granule biogenesis and maturation.
AB  - In the regulated secretory pathway, secretory granules (SGs) store peptide
      hormones that are released on demand. SGs are formed at the trans-Golgi network
      and must undergo a maturation process to become responsive to secretagogues. The
      production of mature SGs requires concentrating newly synthesized soluble content
      proteins in granules whose membranes contain the appropriate integral membrane
      proteins. The mechanisms underlying the sorting of soluble and integral membrane
      proteins destined for SGs from other proteins are not yet well understood. For
      soluble proteins, luminal pH and divalent metals can affect aggregation and
      interaction with surrounding membranes. The trafficking of granule membrane
      proteins can be controlled by both luminal and cytosolic factors. Cytosolic
      adaptor proteins (APs), which recognize the cytosolic domains of proteins that
      span the SG membrane, have been shown to play essential roles in the assembly of
      functional SGs. Adaptor protein 1A (AP-1A) is known to interact with specific
      motifs in its cargo proteins and with the clathrin heavy chain, contributing to
      the formation of a clathrin coat. AP-1A is present in patches on immature SG
      membranes, where it removes cargo and facilitates SG maturation. AP-1A
      recruitment to membranes can be modulated by Phosphofurin Acidic Cluster Sorting
      protein 1 (PACS-1), a cytosolic protein which interacts with both AP-1A and cargo
      that has been phosphorylated by casein kinase II. A cargo/PACS-1/AP-1A complex is
      necessary to drive the appropriate transport of several cargo proteins within the
      regulated secretory pathway. The Golgi-localized, gamma-ear containing, ADP
      ribosylation factor binding (GGA) family of APs serve a similar role. We review
      the functions of AP-1A, PACS-1, and GGAs in facilitating the retrieval of
      proteins from immature SGs and review examples of cargo proteins whose
      trafficking within the regulated secretory pathway is governed by APs. 

PMID- 23966982
TI  - Glutamate and GABA in Appetite Regulation.
AB  - Appetite is regulated by a coordinated interplay between gut, adipose tissue, and
      brain. A primary site for the regulation of appetite is the hypothalamus where
      interaction between orexigenic neurons, expressing Neuropeptide Y/Agouti-related
      protein, and anorexigenic neurons, expressing Pro-opiomelanocortin
      cocaine/Amphetamine-related transcript, controls energy homeostasis. Within the
      hypothalamus, several peripheral signals have been shown to modulate the activity
      of these neurons, including the orexigenic peptide ghrelin and the anorexigenic
      hormones insulin and leptin. In addition to the accumulated knowledge on
      neuropeptide signaling, presence and function of amino acid neurotransmitters in
      key hypothalamic neurons brought a new light into appetite regulation. Therefore,
      the principal aim of this review will be to describe the current knowledge of the
      role of amino acid neurotransmitters in the mechanism of neuronal activation
      during appetite regulation and the associated neuronal-astrocytic metabolic
      coupling mechanisms. Glutamate and GABA dominate synaptic transmission in the
      hypothalamus and administration of their receptors agonists into hypothalamic
      nuclei stimulates feeding. By using (13)C High-Resolution Magic Angle Spinning
      Nuclear Magnetic Resonance spectroscopy based analysis, the Cerdan group has
      shown that increased neuronal firing in mice hypothalamus, as triggered by
      appetite during the feeding-fasting paradigm, may stimulate the use of lactate as
      neuronal fuel leading to increased astrocytic glucose consumption and glycolysis.
      Moreover, fasted mice showed increased hypothalamic [2-(13)C]GABA content, which
      may be explained by the existence of GABAergic neurons in key appetite regulation
      hypothalamic nuclei. Interestingly, increased [2-(13)C]GABA concentration in the
      hypothalamus of fasted animals appears to result mainly from reduction in GABA
      metabolizing pathways, rather than increased GABA synthesis by augmented activity
      of the glutamate-glutamine-GABA cycle. 

PMID- 23966983
TI  - Off-season biogenic volatile organic compound emissions from heath mesocosms:
      responses to vegetation cutting.
AB  - Biogenic volatile organic compounds (BVOCs) affect both atmospheric processes and
      ecological interactions. Our primary aim was to differentiate between BVOC
      emissions from above- and belowground plant parts and heath soil outside the
      growing season. The second aim was to assess emissions from herbivory, mimicked
      by cutting the plants. Mesocosms from a temperate Deschampsia flexuosa-dominated
      heath ecosystem and a subarctic mixed heath ecosystem were either left intact,
      the aboveground vegetation was cut, or all plant parts (including roots) were
      removed. For 3-5 weeks, BVOC emissions were measured in growth chambers by an
      enclosure method using gas chromatography-mass spectrometry. CO2 exchange, soil
      microbial biomass, and soil carbon and nitrogen concentrations were also
      analyzed. Vegetation cutting increased BVOC emissions by more than 20-fold, and
      the induced compounds were mainly eight-carbon compounds and sesquiterpenes. In
      the Deschampsia heath, the overall low BVOC emissions originated mainly from
      soil. In the mixed heath, root, and soil emissions were negligible. Net BVOC
      emissions from roots and soil of these well-drained heaths do not significantly
      contribute to ecosystem emissions, at least outside the growing season. If insect
      outbreaks become more frequent with climate change, ecosystem BVOC emissions will
      periodically increase due to herbivory. 

PMID- 23966984
TI  - Environmental impacts on the diversity of methane-cycling microbes and their
      resultant function.
AB  - Methane is an important anthropogenic greenhouse gas that is produced and
      consumed in soils by microorganisms responding to micro-environmental conditions.
      Current estimates show that soil consumption accounts for 5-15% of methane
      removed from the atmosphere on an annual basis. Recent variability in atmospheric
      methane concentrations has called into question the reliability of estimates of
      methane consumption and calls for novel approaches in order to predict future
      atmospheric methane trends. This review synthesizes the environmental and
      climatic factors influencing the consumption of methane from the atmosphere by
      non-wetland, terrestrial soil microorganisms. In particular, we focus on
      published efforts to connect community composition and diversity of methane
      cycling microbial communities to observed rates of methane flux. We find abundant
      evidence for direct connections between shifts in the methane-cycling microbial
      community, due to climate and environmental changes, and observed methane flux
      levels. These responses vary by ecosystem and associated vegetation type. This
      information will be useful in process-based models of ecosystem methane flux
      responses to shifts in environmental and climatic parameters. 

PMID- 23966985
TI  - Functional comparison of antisense proteins of HTLV-1 and HTLV-2 in viral
      pathogenesis.
AB  - The production of antisense transcripts from the 3' long terminal repeat (LTR) in
      human T-lymphotropic retroviruses has now been clearly demonstrated. After the
      identification of the antisense strand-encoded human T-lymphotropic virus type 1
      (HTLV-1) bZIP (HBZ) factor, we reported that HBZ could interact with CRE-binding
      protein (CREB) transcription factors and consequently turn off the important
      activating potential of the viral Tax protein on HTLV-1 5' LTR promoter activity.
      We have recently accumulated new results demonstrating that antisense transcripts
      also exist in HTLV-2, -3, and -4. Furthermore, our data have confirmed the
      existence of encoded proteins from these antisense transcripts (termed antisense
      proteins of HTLVs or APHs). APHs are also involved in the down-regulation of Tax
      dependent viral transcription. In this review, we will focus on the different
      molecular mechanisms used by HBZ and APH-2 to control viral expression. While HBZ
      interacts with CREB through its basic zipper domain, APH-2 binds to this cellular
      factor through a five amino acid motif localized in its carboxyl terminus.
      Moreover, unlike APH-2, HBZ possesses an N-terminal activation domain that also
      contributes to the inhibition of the viral transcription by interacting with the
      KIX domain of p300/CBP. On the other hand, HBZ was found to induce T cell
      proliferation while APH-2 was unable to promote such proliferation.
      Interestingly, HTLV-2 has not been causally linked to human T cell leukemia,
      while HTLV-1 is responsible for the development of the adult T cell
      leukemia/lymphoma. We will further discuss the possible role played by antisense
      proteins in the establishment of pathologies induced by viral infection. 

PMID- 23966986
TI  - Impact of seasonal hydrological variation on the distributions of tetraether
      lipids along the Amazon River in the central Amazon basin: implications for the
      MBT/CBT paleothermometer and the BIT index.
AB  - Suspended particulate matter (SPM) was collected along the Amazon River in the
      central Amazon basin and in three tributaries during the rising water (RW), high
      water (HW), falling water (FW) and low water (LW) season. Changes in the
      concentration and the distribution of branched glycerol dialkyl glycerol
      tetraethers (brGDGTs), i.e., the methylation index of branched tetraethers (MBT)
      and the cyclization of brGDGTs (CBT), were seen in the Amazon main stem. The
      highest concentration of core lipid (CL) brGDGTs normalized to particulate
      organic carbon (POC) was found during the HW season. During the HW season the MBT
      and CBT in the Amazon main stem was also most similar to that of lowland Amazon
      (terra firme) soils, indicating that the highest input of soil-derived brGDGTs
      occurred due to increased water runoff. During the other seasons the MBT and CBT
      indicated an increased influence of in situ production of brGDGTs even though
      soils remained the main source of brGDGTs. Our results reveal that the influence
      of seasonal variation is relatively small, but can be clearly detected.
      Crenarchaeol was mostly produced in the river. Its concentration was lower during
      the HW season compared to that of the other seasons. Hence, our study shows the
      complexity of processes that influence the GDGT distribution during the transport
      from land to ocean. It emphasizes the importance of a detailed study of a river
      basin to interpret the MBT/CBT and BIT records for paleo reconstructions in
      adjacent marine setting. 

PMID- 23966987
TI  - Ciliates learn to diagnose and correct classical error syndromes in mating
      strategies.
AB  - Preconjugal ciliates learn classical repetition error-correction codes to
      safeguard mating messages and replies from corruption by "rivals" and local
      ambient noise. Because individual cells behave as memory channels with Szilard
      engine attributes, these coding schemes also might be used to limit, diagnose,
      and correct mating-signal errors due to noisy intracellular information
      processing. The present study, therefore, assessed whether heterotrich ciliates
      effect fault-tolerant signal planning and execution by modifying engine
      performance, and consequently entropy content of codes, during mock cell-cell
      communication. Socially meaningful serial vibrations emitted from an ambiguous
      artificial source initiated ciliate behavioral signaling performances known to
      advertise mating fitness with varying courtship strategies. Microbes, employing
      calcium-dependent Hebbian-like decision making, learned to diagnose then correct
      error syndromes by recursively matching Boltzmann entropies between signal
      planning and execution stages via "power" or "refrigeration" cycles. All eight
      serial contraction and reversal strategies incurred errors in entropy magnitude
      by the execution stage of processing. Absolute errors, however, subtended
      expected threshold values for single bit-flip errors in three-bit replies,
      indicating coding schemes protected information content throughout signal
      production. Ciliate preparedness for vibrations selectively and significantly
      affected the magnitude and valence of Szilard engine performance during modal and
      non-modal strategy corrective cycles. But entropy fidelity for all replies mainly
      improved across learning trials as refinements in engine efficiency. Fidelity
      neared maximum levels for only modal signals coded in resilient three-bit
      repetition error-correction sequences. Together, these findings demonstrate
      microbes can elevate survival/reproductive success by learning to implement
      classical fault-tolerant information processing in social contexts. 

PMID- 23966988
TI  - Genomic and evolutionary aspects of phytoplasmas.
AB  - Parasitic bacteria that infect eukaryotes, such as animals and plants, often have
      reduced genomes, having lost important metabolic genes as a result of their host
      dependent life cycles. Genomic sequencing of these bacteria has revealed their
      survival strategies and adaptations to parasitism. Phytoplasmas (class
      Mollicutes, genus 'Candidatus Phytoplasma') are intracellular bacterial pathogens
      of plants and insects and cause devastating yield losses in diverse low- and high
      value crops worldwide. The complete genomic sequences of four Candidatus
      Phytoplasma species have been reported. The genomes encode even fewer metabolic
      functions than other bacterial genomes do, which may be the result of reductive
      evolution as a consequence of their life as an intracellular parasite. This
      review summarizes current knowledge of the diversity and common features of
      phytoplasma genomes, including the factors responsible for pathogenicity. 

PMID- 23966990
TI  - Impact of DNA damaging agents on genome-wide transcriptional profiles in two
      marine Synechococcus species.
AB  - Marine microorganisms, particularly those residing in coastal areas, may come in
      contact with any number of chemicals of environmental or xenobiotic origin. The
      sensitivity and response of marine cyanobacteria to such chemicals is, at
      present, poorly understood. We have looked at the transcriptional response of
      well characterized Synechococcus open ocean (WH8102) and coastal (CC9311)
      isolates to two DNA damaging agents, mitomycin C and ethidium bromide, using
      whole-genome expression microarrays. The coastal strain showed differential
      regulation of a larger proportion of its genome following "shock" treatment with
      each agent. Many of the orthologous genes in these strains, including those
      encoding sensor kinases, showed different transcriptional responses, with the
      CC9311 genes more likely to show significant changes in both treatments. While
      the overall response of each strain was considerably different, there were
      distinct transcriptional responses common to both strains observed for each DNA
      damaging agent, linked to the mode of action of each chemical. In both CC9311 and
      WH8102 there was evidence of SOS response induction under mitomycin C treatment,
      with genes recA, lexA and umuC significantly upregulated in this experiment but
      not under ethidium bromide treatment. Conversely, ethidium bromide treatment
      tended to result in upregulation of the DNA-directed RNA polymerase genes, not
      observed following mitomycin C treatment. Interestingly, a large number of genes
      residing on putative genomic island regions of each genome also showed
      significant upregulation under one or both chemical treatments. 

PMID- 23966989
TI  - Tax-1 and Tax-2 similarities and differences: focus on post-translational
      modifications and NF-kappaB activation.
AB  - Although human T cell leukemia virus type 1 and 2 (HTLV-1 and HTLV-2) share
      similar genetic organization, they have major differences in their pathogenesis
      and disease manifestation. HTLV-1 is capable of transforming T lymphocytes in
      infected patients resulting in adult T cell leukemia/lymphoma whereas HTLV-2 is
      not clearly associated with lymphoproliferative diseases. Numerous studies have
      provided accumulating evidence on the involvement of the viral transactivators
      Tax-1 versus Tax-2 in T cell transformation. Tax-1 is a potent transcriptional
      activator of both viral and cellular genes. Tax-1 post-translational
      modifications and specifically ubiquitylation and SUMOylation have been
      implicated in nuclear factor-kappaB (NF-kappaB) activation and may contribute to
      its transformation capacity. Although Tax-2 has similar protein structure
      compared to Tax-1, the two proteins display differences both in their protein
      protein interaction and activation of signal transduction pathways. Recent
      studies on Tax-2 have suggested ubiquitylation and SUMOylation independent
      mechanisms of NF-kappaB activation. In this present review, structural and
      functional differences between Tax-1 and Tax-2 will be summarized. Specifically,
      we will address their subcellular localization, nuclear trafficking and their
      effect on cellular regulatory proteins. A special attention will be given to Tax
      1/Tax-2 post-translational modification such as ubiquitylation, SUMOylation,
      phosphorylation, acetylation, NF-kappaB activation, and protein-protein
      interactions involved in oncogenecity both in vivo and in vitro. 

PMID- 23966992
TI  - High prevalence of fecal carriage of extended spectrum beta-lactamase/AmpC
      producing Enterobacteriaceae in cats and dogs.
AB  - Extended-spectrum-beta-lactamase (ESBL)/AmpC producing Enterobacteriaceae have
      been reported worldwide amongst isolates obtained from humans, food-producing
      animals, companion animals, and environmental sources. However, data on
      prevalence of fecal carriage of ESBL/AmpC producing Enterobacteriaceae in healthy
      companion animals is limited. This pilot study describes the prevalence of
      ESBL/AmpC encoding genes in healthy cats and dogs, and cats and dogs with
      diarrhea. Twenty fecal samples of each group were cultured on MacConkey agar
      supplemented with 1 mg/L cefotaxime and in LB-enrichment broth supplemented with
      1 mg/L cefotaxime, which was subsequently inoculated on MacConkey agar
      supplemented with 1 mg/L cefotaxime. ESBL/AmpC genes were identified using the
      Check-Points CT103 micro array kit and subsequently by sequencing analysis.
      Chromosomal ampC promoter mutations were detected by PCR and sequencing analysis.
      From the healthy and diarrheic dogs, respectively 45 and 55% were positive for
      Escherichia coli with reduced susceptibility for cefotaxime. From the healthy and
      diarrheic cats, the estimated prevalence was respectively 0 and 25%. One
      diarrheic cat was positive for both reduced susceptible E. coli and Proteus
      mirabilis. The ESBL/AmpC genes found in this study were mainly bla CTX-M-1, but
      also bla CTX-M-14, bla CTX-M-15, bla TEM-52-StPaul, bla SHV-12, and bla CMY-2
      were detected. This pilot study showed that the prevalence of ESBL/AmpC producing
      Enterobacteriaceae in healthy and diarrheic dogs, and diarrheic cats was
      relatively high. Furthermore, the genes found were similar to those found in
      isolates of both human and food-producing animal origin. However, since the size
      of this study was relatively small, extrapolation of the data to the general
      population of cats and dogs should be done with great care. 

PMID- 23966991
TI  - Biotic acts of antibiotics.
AB  - Biological functions of antibiotics are not limited to killing. The most likely
      function of antibiotics in natural microbial ecosystems is signaling. Does this
      signaling function of antibiotics also extend to the eukaryotic - in particular
      mammalian - cells? In this review, the host modulating properties of three
      classes of antibiotics (macrolides, tetracyclines, and beta-lactams) will be
      briefly discussed. Antibiotics can be effective in treatment of a broad spectrum
      of diseases and pathological conditions other than those of infectious etiology
      and, in this capacity, may find widespread applications beyond the intended
      antimicrobial use. This use, however, should not compromise the primary function
      antibiotics are used for. The biological background for this inter-kingdom
      signaling is also discussed. 

PMID- 23966993
TI  - Arginase 1: an unexpected mediator of pulmonary capillary barrier dysfunction in
      models of acute lung injury.
AB  - The integrity of epithelial and endothelial barriers in the lower airspaces of
      the lungs has to be tightly regulated, in order to prevent leakage and to assure
      efficient gas exchange between the alveoli and capillaries. Both G(-) and G(+)
      bacterial toxins, such as lipopolysaccharide and pneumolysin, respectively, can
      be released in high concentrations within the pulmonary compartments upon
      antibiotic treatment of patients suffering from acute respiratory distress
      syndrome (ARDS) or severe pneumonia. These toxins are able to impair endothelial
      barrier function, either directly, or indirectly, by induction of pro
      inflammatory mediators and neutrophil sequestration. Toxin-induced endothelial
      hyperpermeability can involve myosin light chain phosphorylation and/or
      microtubule rearrangement. Endothelial nitric oxide synthase (eNOS) was proposed
      to be a guardian of basal barrier function, since eNOS knock-out mice display an
      impaired expression of inter-endothelial junction proteins and as such an
      increased vascular permeability, as compared to wild type mice. The enzyme
      arginase, the activity of which can be regulated by the redox status of the cell,
      exists in two isoforms - arginase 1 (cytosolic) and arginase 2 (mitochondrial) -
      both of which can be expressed in lung microvascular endothelial cells. Upon
      activation, arginase competes with eNOS for the substrate l-arginine, as such
      impairing eNOS-dependent NO generation and promoting reactive oxygen species
      generation by the enzyme. This mini-review will discuss recent findings regarding
      the interaction between bacterial toxins and arginase during acute lung injury
      and will as such address the role of arginase in bacterial toxin-induced
      pulmonary endothelial barrier dysfunction. 

PMID- 23966994
TI  - Peripherally induced tregs - role in immune homeostasis and autoimmunity.
AB  - Thymically derived Foxp3(+) regulatory T cells (tTregs) constitute a unique T
      cell lineage that is essential for maintaining immune tolerance to self and
      immune homeostasis. However, Foxp3 can also be turned on in conventional T cells
      as a consequence of antigen exposure in the periphery, under both non
      inflammatory and inflammatory conditions. These so-called peripheral Tregs
      (pTregs) participate in the control of immunity at sites of inflammation,
      especially at the mucosal surfaces. Although numerous studies have assessed in
      vitro generated Tregs (termed induced or iTregs), these cells most often do not
      recapitulate the functional or phenotypic characteristics of in vivo generated
      pTregs. Thus, there are still many unanswered questions regarding the T cell
      receptor (TCR) repertoire and function of pTregs as well as conditions under
      which they are generated in vivo, and the degree to which these characteristics
      identify specialized features of pTregs versus features that are shared with
      tTregs. In this review, we summarize the current state of our understanding of
      pTregs and their relationship to the tTreg subset. We describe the recent
      discovery of unique cell surface markers and transcription factors (including
      Neuropilin-1 and Helios) that can be used to distinguish tTreg and pTreg subsets
      in vivo. Additionally, we discuss how the improved ability to distinguish these
      subsets provided new insights into the biology of tTregs versus pTregs and
      suggested differences in their function and TCR repertoire, consistent with a
      unique role of pTregs in certain inflammatory settings. Finally, these recent
      advances will be used to speculate on the role of individual Treg subsets in both
      tolerance and autoimmunity. 

PMID- 23966995
TI  - Early detection of simian immunodeficiency virus in the central nervous system
      following oral administration to rhesus macaques.
AB  - The timing of HIV dissemination to the central nervous system (CNS) has the
      potential to have important implications regarding HIV disease progression and
      treatment. The earlier HIV enters the CNS the more difficult it might be to
      remove with antiretroviral therapy. Alternatively, HIV may only enter the CNS
      later in the course of disease as a result of disruption of the blood-brain
      barrier. We utilized the simian immunodeficiency virus (SIV) infection of rhesus
      macaques to evaluate the oral route of infection and the subsequent spread of SIV
      to the CNS during the acute infection phase. A high dose oral SIV challenge was
      utilized to ensure a successful infection and permit the evaluation of CNS spread
      during the first 1-14 days post-infection. Ultrasensitive nested PCR was used to
      detect SIV gag DNA in the brains of macaques at 1-2 days post-infection and
      identified SIV gag DNA in the brain tissues from three of four macaques. This SIV
      DNA was also present following perfusion of the macaque brains, providing
      evidence that it was not residing in the circulating blood but in the brain
      tissue itself. The diversity of the viral envelope V1-V2 region at early times
      post-infection indicated that the brain viral variants were similar to variants
      obtained from lymph nodes. This genetic similarity between SIV obtained from
      lymphoid and brain tissues suggests that the founder population of viral species
      entered and subsequently spread without any evidence of brain-specific SIV
      selection. The relatively rapid appearance of SIV within the CNS tissue following
      oral transmission may also occur during HIV transmission where it may impact
      disease course as well as representing a challenge for long-term therapies and
      future viral eradication modalities. 

PMID- 23966997
TI  - Increased serum type I interferon activity in organ-specific autoimmune
      disorders: clinical, imaging, and serological associations.
AB  - BACKGROUND: Activation of the type I interferon (IFN) pathway has been implicated
      in the pathogenesis of systemic autoimmune disorders but its role in the
      pathogenesis of organ-specific autoimmunity is limited. We tested the hypothesis
      that endogenous expression of type I IFN functional activity contributes to the
      pathogenesis of autoimmune thyroid disease (ATD) and type I diabetes (T1DM).
      METHODS: We studied 39 patients with ATD and 39 age and sex matched controls
      along with 88 T1DM patients and 46 healthy matched controls respectively.
      Available clinical and serological parameters were recorded by chart review, and
      thyroid ultrasound was performed in 17 ATD patients. Type I IFN serum activity
      was determined in all subjects using a reporter cell assay. The rs1990760 SNP of
      the interferon-induced helicase 1 gene was genotyped in ATD patients. RESULTS:
      Serum type I IFN activity was increased in patients with ATD and T1DM compared to
      controls (p-values: 0.002 and 0.04, respectively). ATD patients with high type I
      IFN serum activity had increased prevalence of antibodies against thyroglobulin
      (anti-Tg) and cardiopulmonary manifestations compared to those with low IFN
      activity. Additionally, the presence of micronodules on thyroid ultrasound was
      associated with higher type I IFN levels. In patients with T1DM, high IFN levels
      were associated with increased apolipoprotein-B levels. CONCLUSION: Serum type I
      IFN activity is increased in ATD and T1DM and is associated with specific
      clinical, serological, and imaging features. These findings may implicate type I
      IFN pathway in the pathogenesis of specific features of organ-specific
      autoimmunity.

PMID- 23966996
TI  - Vasomotor regulation of coronary microcirculation by oxidative stress: role of
      arginase.
AB  - Overproduction of reactive oxygen species, i.e., oxidative stress, is associated
      with the activation of redox signaling pathways linking to inflammatory insults
      and cardiovascular diseases by impairing endothelial function and consequently
      blood flow dysregulation due to microvascular dysfunction. This review focuses on
      the regulation of vasomotor function in the coronary microcirculation by
      endothelial nitric oxide (NO) during oxidative stress and inflammation related to
      the activation of L-arginine consuming enzyme arginase. Superoxide produced in
      the vascular wall compromises vasomotor function by not only scavenging
      endothelium-derived NO but also inhibiting prostacyclin synthesis due to
      formation of peroxynitrite. The upregulation of arginase contributes to the
      deficiency of endothelial NO and microvascular dysfunction in various vascular
      diseases by initiating or following oxidative stress and inflammation. Hydrogen
      peroxide, a diffusible and stable oxidizing agent, exerts vasodilator function
      and plays important roles in the physiological regulation of coronary blood flow.
      In occlusive coronary ischemia, the release of hydrogen peroxide from the
      microvasculature helps to restore vasomotor function of coronary collateral
      microvessels with exercise training. However, excessive production and prolonged
      exposure of microvessels to hydrogen peroxide impairs NO-mediated endothelial
      function by reducing L-arginine availability through hydroxyl radical-dependent
      upregulation of arginase. The redox signaling can be a double-edged sword in the
      microcirculation, which helps tissue survival in one way by improving vasomotor
      regulation and elicits oxidative stress and tissue injury in the other way by
      causing vascular dysfunction. The impact of vascular arginase on the development
      of vasomotor dysfunction associated with angiotensin II receptor activation,
      hypertension, ischemia-reperfusion, hypercholesterolemia, and inflammatory
      insults is discussed. 

PMID- 23966998
TI  - Peripheral tissue homing receptor control of naive, effector, and memory CD8 T
      cell localization in lymphoid and non-lymphoid tissues.
AB  - T cell activation induces homing receptors that bind ligands on peripheral tissue
      vasculature, programing movement to sites of infection and injury. There are
      three major types of CD8 effector T cells based on homing receptor expression,
      which arise in distinct lymphoid organs. Recent publications indicate that naive,
      effector, and memory T cell migration is more complex than once thought; while
      many effectors enter peripheral tissues, some re-enter lymph nodes (LN), and
      contain central memory precursors. LN re-entry can depend on CD62L or peripheral
      tissue homing receptors. Memory T cells in LN tend to express the same homing
      receptors as their forebears, but often are CD62Lneg. Homing receptors also
      control CD8 T cell tumor entry. Tumor vasculature has low levels of many
      peripheral tissue homing receptor ligands, but portions of it resemble high
      endothelial venules (HEV), enabling naive T cell entry, activation, and
      subsequent effector activity. This vasculature is associated with positive
      prognoses in humans, suggesting it may sustain ongoing anti-tumor responses.
      These findings reveal new roles for homing receptors expressed by naive,
      effector, and memory CD8 T cells in controlling entry into lymphoid and non
      lymphoid tissues. 

PMID- 23966999
TI  - Control of Zn uptake in Arabidopsis halleri: a balance between Zn and Fe.
AB  - Zinc (Zn) is an essential plant micronutrient but is toxic in excess. To cope
      with excess Zn, plant species possess a strict metal homeostasis mechanism. The
      Zn hyperaccumulator Arabidopsis halleri has developed various adaptive mechanisms
      involving uptake, chelation, translocation and sequestration of Zn. In this mini
      review, we broadly discuss the different Zn tolerance mechanisms and then focus
      on controlled Zn uptake in A. halleri. Members of the ZRT/IRT-like protein (ZIP)
      family of metal transporters are mainly regulated by Zn and are involved in Zn
      uptake. A few members of the ZIP family, such as IRT1 and IRT2, are regulated by
      iron (Fe) and can transport multi-metals, including Zn, Fe, Mn, Cd, and Co. This
      mini-review also discusses the differential expression of multiple metal ZIP
      transporters in A. halleri and A. thaliana, a non-hyperaccumulator, with Zn
      exposure as well as Fe deficiency and their role in controlled Zn uptake and
      tolerance. 

PMID- 23967000
TI  - Belowground neighbor perception in Arabidopsis thaliana studied by transcriptome
      analysis: roots of Hieracium pilosella cause biotic stress.
AB  - Root-root interactions are much more sophisticated than previously thought, yet
      the mechanisms of belowground neighbor perception remain largely obscure. Genome
      wide transcriptome analyses allow detailed insight into plant reactions to
      environmental cues. A root interaction trial was set up to explore both
      morphological and whole genome transcriptional responses in roots of Arabidopsis
      thaliana in the presence or absence of an inferior competitor, Hieracium
      pilosella. Neighbor perception was indicated by Arabidopsis roots predominantly
      growing away from the neighbor (segregation), while solitary plants placed more
      roots toward the middle of the pot. Total biomass remained unaffected. Database
      comparisons in transcriptome analysis revealed considerable similarity between
      Arabidopsis root reactions to neighbors and reactions to pathogens. Detailed
      analyses of the functional category "biotic stress" using MapMan tools found the
      sub-category "pathogenesis-related proteins" highly significantly induced. A
      comparison to a study on intraspecific competition brought forward a core of
      genes consistently involved in reactions to neighbor roots. We conclude that
      beyond resource depletion roots perceive neighboring roots or their associated
      microorganisms by a relatively uniform mechanism that involves the strong
      induction of pathogenesis-related proteins. In an ecological context the findings
      reveal that belowground neighbor detection may occur independently of resource
      depletion, allowing for a time advantage for the root to prepare for potential
      interactions. 

PMID- 23967001
TI  - Rhizosphere wettability decreases with root age: a problem or a strategy to
      increase water uptake of young roots?
AB  - As plant roots take up water and the soil dries, water depletion is expected to
      occur in the vicinity of roots, the so called rhizosphere. However, recent
      experiments showed that the rhizosphere of lupines was wetter than the bulk soil
      during the drying period. Surprisingly, the rhizosphere remained temporarily dry
      after irrigation. Such water dynamics in the rhizosphere can be explained by the
      drying/wetting dynamics of mucilage exuded by roots. The capacity of mucilage to
      hold large volumes of water at negative water potential may favor root water
      uptake. However, mucilage hydrophobicity after drying may temporarily limit the
      local water uptake after irrigation. The effects of such rhizosphere dynamics are
      not yet understood. In particular, it is not known how the rhizosphere dynamics
      vary along roots and as a function of soil water content. My hypothesis was that
      the rewetting rate of the rhizosphere is primarily function of root age. Neutron
      radiography was used to monitor how the rhizosphere water dynamics vary along the
      root systems of lupines during drying/wetting cycles of different duration. The
      radiographs showed a fast and almost immediate rewetting of the rhizosphere of
      the distal root segments, in contrast to a slow rewetting of the rhizosphere of
      the proximal segments. The rewetting rate of the rhizosphere was not function of
      the water content before irrigation, but it was function of time. It is concluded
      that rhizosphere hydrophobicity is not uniform along roots, but it covers only
      the older and proximal root segments, while the young root segments are
      hydraulically well-connected to the soil. I included these rhizosphere dynamics
      in a microscopic model of root water uptake. In the model, the relation between
      water content and water potential in the rhizosphere is not unique and it varies
      over time, and the rewetting rate of the rhizosphere decreases with time. The
      rhisosphere variability seems an optimal adaptation strategy to increase the
      water uptake of young root segments, which possibly reached new available water,
      and partly disconnect the old root segments from the already depleted soil. 

PMID- 23967002
TI  - Overoxidation of chloroplast 2-Cys peroxiredoxins: balancing toxic and signaling
      activities of hydrogen peroxide.
AB  - Photosynthesis, the primary source of biomass and oxygen into the biosphere,
      involves the transport of electrons in the presence of oxygen and, therefore,
      chloroplasts constitute an important source of reactive oxygen species, including
      hydrogen peroxide. If accumulated at high level, hydrogen peroxide may exert a
      toxic effect; however, it is as well an important second messenger. In order to
      balance the toxic and signaling activities of hydrogen peroxide its level has to
      be tightly controlled. To this end, chloroplasts are equipped with different
      antioxidant systems such as 2-Cys peroxiredoxins (2-Cys Prxs), thiol-based
      peroxidases able to reduce hydrogen and organic peroxides. At high peroxide
      concentrations the peroxidase function of 2-Cys Prxs may become inactivated
      through a process of overoxidation. This inactivation has been proposed to
      explain the signaling function of hydrogen peroxide in eukaryotes, whereas in
      prokaryotes, the 2-Cys Prxs of which were considered to be insensitive to
      overoxidation, the signaling activity of hydrogen peroxide is less relevant. Here
      we discuss the current knowledge about the mechanisms controlling 2-Cys Prx
      overoxidation in chloroplasts, organelles with an important signaling function in
      plants. Given the prokaryotic origin of chloroplasts, we discuss the occurrence
      of 2-Cys Prx overoxidation in cyanobacteria with the aim of identifying
      similarities between chloroplasts and their ancestors regarding their response to
      hydrogen peroxide. 

PMID- 23967003
TI  - Barley responses to combined waterlogging and salinity stress: separating effects
      of oxygen deprivation and elemental toxicity.
AB  - Salinity and waterlogging are two major factors affecting crop production around
      the world and often occur together (e.g., salt brought to the surface by rising
      water tables). While the physiological and molecular mechanisms of plant
      responses to each of these environmental constraints are studied in detail, the
      mechanisms underlying plant tolerance to their combined stress are much less
      understood. In this study, whole-plant physiological responses to
      individual/combined salinity and waterlogging stresses were studied using two
      barley varieties grown in either vermiculite (semi-hydroponics) or sandy loam.
      Two weeks of combined salinity and waterlogging treatment significantly decreased
      plant biomass, chlorophyll content, maximal quantum efficiency of PSII and water
      content (WC) in both varieties, while the percentage of chlorotic and necrotic
      leaves and leaf sap osmolality increased. The adverse effects of the combined
      stresses were much stronger in the waterlogging-sensitive variety Naso Nijo.
      Compared with salinity stress alone, the combined stress resulted in a 2-fold
      increase in leaf Na(+), but a 40% decrease in leaf K(+) content. Importantly, the
      effects of the combined stress were more pronounced in sandy loam compared with
      vermiculite and correlated with changes in the soil redox potential and
      accumulation of Mn and Fe in the waterlogged soils. It is concluded that hypoxia
      alone is not a major factor determining differential plant growth under adverse
      stress conditions, and that elemental toxicities resulting from changes in soil
      redox potential have a major impact on genotypic differences in plant
      physiological and agronomical responses. These results are further discussed in
      the context of plant breeding for waterlogging stress tolerance. 

PMID- 23967004
TI  - Cross-talk of nitric oxide and reactive oxygen species in plant programed cell
      death.
AB  - In plants, programed cell death (PCD) is an important mechanism to regulate
      multiple aspects of growth and development, as well as to remove damaged or
      infected cells during responses to environmental stresses and pathogen attacks.
      Under biotic and abiotic stresses, plant cells exhibit a rapid synthesis of
      nitric oxide (NO) and a parallel accumulation of reactive oxygen species (ROS).
      Frequently, these responses trigger a PCD process leading to an intrinsic
      execution of plant cells. The accumulating evidence suggests that both NO and ROS
      play key roles in PCD. These redox active small molecules can trigger cell death
      either independently or synergistically. Here we summarize the recent progress on
      the cross-talk of NO and ROS signals in the hypersensitive response, leaf
      senescence, and other kinds of plant PCD caused by diverse cues. 

PMID- 23967005
TI  - Mitochondrial ferritin is a functional iron-storage protein in cucumber (Cucumis
      sativus) roots.
AB  - In plants, intracellular Fe trafficking must satisfy chloroplasts' and
      mitochondrial demands for Fe without allowing its accumulation in the organelles
      in dangerous redox-active forms. Protein ferritin is involved in such homeostatic
      control, however its functional role in mitochondria, differently from its role
      in chloroplasts, is still matter of debate. To test ferritin functionality as a
      24-mer Fe-storage complex in mitochondria, cucumber seedlings were grown under
      different conditions of Fe supply (excess, control, deficiency) and mitochondria
      were purified from the roots. A ferritin monomer of around 25 KDa was detected by
      SDS-PAGE in Fe-excess root mitochondria, corresponding to the annotated
      Csa5M215130/XP_004163524 protein: such a monomer is barely detectable in the
      control mitochondria and not at all in the Fe-deficient ones. Correspondingly,
      the ferritin 24-mer complex is abundant in root mitochondria from Fe-excess
      plants and it stores Fe as Fe(III): such a complex is also detectable, though to
      a much smaller extent, in control mitochondria, but not in Fe-deficient ones.
      Cucumber ferritin Csa5M215130/XP_004163524 is therefore a functional Fe(III)
      store in root mitochondria and its abundance is dependent on the Fe nutritional
      status of the plant. 

PMID- 23967006
TI  - The influence of inorganic nitrogen fertilizer forms on micronutrient
      retranslocation and accumulation in grains of winter wheat.
AB  - The fortification of cereal grains with metal micronutrients is a major target to
      combat human malnutrition of Fe and Zn. Based on recent studies showing that N
      fertilization can promote Fe and Zn accumulation in cereal grains, we
      investigated here the influence of nitrate- or ammonium-based N fertilization on
      the accumulation of Fe, Zn, and Cu as well as metal chelator pools in flag leaves
      and grains of winter wheat. Fertilization with either N form increased the
      concentrations of N and of the metal chelator nicotianamine (NA) in green leaves,
      while 2'-deoxymugineic acid (DMA) remained unaffected. Despite the differential
      response to N fertilization of NA and DMA levels in flag leaves, N fertilization
      remained without any significant effect on the net export of these metals during
      flag leaf senescence, which accounted for approximately one third of the total
      Fe, Zn, or Cu content in leaves. The significant increase in the accumulation of
      Fe, Zn, and Cu found in the grains of primarily ammonium-fertilized plants was
      unrelated to the extent of metal retranslocation from flag leaves. These results
      indicate that an increased N nutritional status of flag leaves promotes the
      accumulation of Fe, Zn, and Cu in flag leaves, which is accompanied by an
      increased pool of NA but not of DMA. With regard to the far higher concentrations
      of DMA relative to NA in leaves and leaf exudates, DMA may be more relevant for
      the mobilization and retranslocation of these metals in high-yielding wheat
      production. 

PMID- 23967007
TI  - At the intersection of non-coding transcription, DNA repair, chromatin structure,
      and cellular senescence.
AB  - It is well accepted that non-coding RNAs play a critical role in regulating gene
      expression. Recent paradigm-setting studies are now revealing that non-coding
      RNAs, other than microRNAs, also play intriguing roles in the maintenance of
      chromatin structure, in the DNA damage response, and in adult human stem cell
      aging. In this review, we will discuss the complex inter-dependent relationships
      among non-coding RNA transcription, maintenance of genomic stability, chromatin
      structure, and adult stem cell senescence. DNA damage-induced non-coding RNAs
      transcribed in the vicinity of the DNA break regulate recruitment of the DNA
      damage machinery and DNA repair efficiency. We will discuss the correlation
      between non-coding RNAs and DNA damage repair efficiency and the potential role
      of changing chromatin structures around double-strand break sites. On the other
      hand, induction of non-coding RNA transcription from the repetitive Alu elements
      occurs during human stem cell aging and hinders efficient DNA repair causing
      entry into senescence. We will discuss how this fine balance between
      transcription and genomic instability may be regulated by the dramatic changes to
      chromatin structure that accompany cellular senescence. 

PMID- 23967008
TI  - Examining marginal sequence similarities between bacterial type III secretion
      system components and Trypanosoma cruzi surface proteins: horizontal gene
      transfer or convergent evolution?
AB  - The cell invasion mechanism of Trypanosoma cruzi has similarities with some
      intracellular bacterial taxa especially regarding calcium mobilization. This
      mechanism is not observed in other trypanosomatids, suggesting that the molecules
      involved in this type of cell invasion were a product of (1) acquisition by
      horizontal gene transfer (HGT); (2) secondary loss in the other trypanosomatid
      lineages of the mechanism inherited since the bifurcation Bacteria-Neomura (1.9
      billion to 900 million years ago); or (3) de novo evolution from non-homologous
      proteins via convergent evolution. Similar to T. cruzi, several bacterial genera
      require increased host cell cytosolic calcium for intracellular invasion. Among
      intracellular bacteria, the mechanism of host cell invasion of genus Salmonella
      is the most similar to T. cruzi. The invasion of Salmonella occurs by contact
      with the host's cell surface and is mediated by the type III secretion system
      (T3SS) that promotes the contact-dependent translocation of effector proteins
      directly into host's cell cytoplasm. Here we provide evidence of distant sequence
      similarities and structurally conserved domains between T. cruzi and Salmonella
      spp T3SS proteins. Exhaustive database searches were directed to a wide range of
      intracellular bacteria and trypanosomatids, exploring sequence patterns for
      comparison of structural similarities and Bayesian phylogenies. Based on our data
      we hypothesize that T. cruzi acquired genes for calcium mobilization mediated
      invasion by ancient HGT from ancestral Salmonella lineages. 

PMID- 23967009
TI  - Effect on lifespan of high yield non-myeloablating transplantation of bone marrow
      from young to old mice.
AB  - Tissue renewal is a well-known phenomenon by which old and dying-off cells of
      various tissues of the body are replaced by progeny of local or circulating stem
      cells (SCs). An interesting question is whether donor SCs are capable to prolong
      the lifespan of an aging organism by tissue renewal. In this work, we
      investigated the possible use of bone marrow (BM) SC for lifespan extension. To
      this purpose, chimeric C57BL/6 mice were created by transplanting BM from young
      1.5-month-old donors to 21.5-month-old recipients. Transplantation was carried
      out by means of a recently developed method which allowed to transplant without
      myeloablation up to 1.5 * 10(8) cells, that is, about 25% of the total BM cells
      of the mouse. As a result, the mean survival time, counting from the age of 21.5
      months, the start of the experiment, was +3.6 and +5.0 (+/-0.1) months for the
      control and experimental groups, respectively, corresponding to a 39 +/- 4%
      increase in the experimental group over the control. In earlier studies on BM
      transplantation, a considerably smaller quantity of donor cells (5 * 10(6)) was
      used, about 1% of the total own BM cells. The recipients before transplantation
      were exposed to a lethal (for control animals) X-ray dose which eliminated the
      possibility of studying the lifespan extension by this method. 

PMID- 23967010
TI  - GraphML specializations to codify ancestral recombinant graphs.
AB  - Software which simulates, infers, or analyzes ancestral recombination graphs
      (ARGs) faces the problem of communicating them. Existing formats omit information
      either about the location of recombinations along the chromosome or the position
      of recombinations relative to the branching topology. We present a specialization
      of GraphML, an XML-based standard for mathematical graphs, for communication of
      ARGs. The GraphML <node> type is specialized to contain the node type, time,
      recombination location, and name. The GraphML <edge> type is specialized to
      contain the ancestral material passed along that edge. This approach, which we
      call ArgML, retains all information in the original ARG. Due to its use of
      established formats ArgML can be parsed, checked and displayed by existing
      software. 

PMID- 23967012
TI  - The mysterious case of the C. elegans gut granule: death fluorescence,
      anthranilic acid and the kynurenine pathway.
AB  - Gut granules are lysosome-like organelles with acidic interiors that are found in
      large numbers within the intestine of the nematode Caenorhabditis elegans. They
      are particularly prominent when viewed under ultraviolet light, which causes them
      to emit intense blue fluorescence. Yet the function of these large and abundant
      organelles in this heavily-studied model organism remains unclear. One
      possibility is that they serve as storage organelles, for example of zinc. A new
      clue to gut granule function is the identification of the blue fluorescent
      material that they contain as a glycosylated form of anthranilic acid, which is
      derived from tryptophan by action of the kynurenine pathway. This compound can
      also serve a surprising role as a natural, endogenous marker of organismal death.

PMID- 23967011
TI  - Structural disorder and the loss of RNA homeostasis in aging and
      neurodegenerative disease.
AB  - Whereas many cases of neurodegenerative disease feature the abnormal accumulation
      of protein, an abundance of recent literature highlights loss of RNA homeostasis
      as a ubiquitous and central feature of pathological states. In some diseases
      expanded repeats have been identified in non-coding regions of disease-associated
      transcripts, calling into question the relevance of protein in the disease
      mechanism. We review the literature in support of a hypothesis that intrinsically
      disordered proteins (proteins that lack a stable three dimensional conformation)
      are particularly sensitive to an age-related decline in maintenance of protein
      homeostasis. The potential consequences for structurally disordered RNA-binding
      proteins are explored, including their aggregation into complexes that could be
      transmitted through a prion-like mechanism. We propose that the spread of
      ribonucleoprotein complexes through the nervous system could propagate a neuronal
      error catastrophe at the level of RNA metabolism. 

PMID- 23967013
TI  - MicroRNA expression profiles in avian haemopoietic cells.
AB  - MicroRNAs (miRNAs) are small, abundant, non-coding RNAs that modulate gene
      expression by interfering with translation or stability of mRNA transcripts in a
      sequence-specific manner. A total of 734 precursor and 996 mature miRNAs have so
      far been identified in the chicken genome. A number of these miRNAs are expressed
      in a cell type-specific manner, and understanding their function requires
      detailed examination of their expression in different cell types. We carried out
      deep sequencing of small RNA populations isolated from stimulated or transformed
      avian haemopoietic cell lines to determine the changes in the expression profiles
      of these important regulatory molecules during these biological events. There
      were significant changes in the expression of a number of miRNAs, including miR
      155, in chicken B cells stimulated with CD40 ligand. Similarly, avian leukosis
      virus (ALV)-transformed DT40 cells also showed changes in miRNA expression in
      relation to the naive cells. Embryonic stem cell line BP25 demonstrated a
      distinct cluster of upregulated miRNAs, many of which were shown previously to be
      involved in embryonic stem cell development. Finally, chicken macrophage cell
      line HD11 showed changes in miRNA profiles, some of which are thought to be
      related to the transformation by v-myc transduced by the virus. This work
      represents the first publication of a catalog of microRNA expression in a range
      of important avian cells and provides insights into the potential roles of miRNAs
      in the hematopoietic lineages of cells in a model non-mammalian species. 

PMID- 23967014
TI  - MATCHCLIP: locate precise breakpoints for copy number variation using CIGAR
      string by matching soft clipped reads.
AB  - Copy number variations (CNVs) are associated with many complex diseases. Next
      generation sequencing data enable one to identify precise CNV breakpoints to
      better under the underlying molecular mechanisms and to design more efficient
      assays. Using the CIGAR strings of the reads, we develop a method that can
      identify the exact CNV breakpoints, and in cases when the breakpoints are in a
      repeated region, the method reports a range where the breakpoints can slide. Our
      method identifies the breakpoints of a CNV using both the positions and CIGAR
      strings of the reads that cover breakpoints of a CNV. A read with a long soft
      clipped part (denoted as S in CIGAR) at its 3'(right) end can be used to identify
      the 5'(left)-side of the breakpoints, and a read with a long S part at the 5' end
      can be used to identify the breakpoint at the 3'-side. To ensure both types of
      reads cover the same CNV, we require the overlapped common string to include both
      of the soft clipped parts. When a CNV starts and ends in the same repeated
      regions, its breakpoints are not unique, in which case our method reports the
      left most positions for the breakpoints and a range within which the breakpoints
      can be incremented without changing the variant sequence. We have implemented the
      methods in a C++ package intended for the current Illumina Miseq and Hiseq
      platforms for both whole genome and exon-sequencing. Our simulation studies have
      shown that our method compares favorably with other similar methods in terms of
      true discovery rate, false positive rate and breakpoint accuracy. Our results
      from a real application have shown that the detected CNVs are consistent with
      zygosity and read depth information. The software package is available at
      http://statgene.med.upenn.edu/softprog.html. 

PMID- 23967016
TI  - TRANSDUCER FIELD IMAGING USING ACOUSTOGRAPHY.
AB  - A common current practice for transducer field mapping is to scan, point-by
      point, a hydrophone element in a 2D raster at various distances from the
      transducer radiating surface. This approach is tedious, requiring hours of
      scanning time to generate full cross-sectional and/or axial field distributions.
      Moreover, the lateral resolution of the field distribution image is dependent on
      the indexing steps between data points. Acoustography is an imaging process in
      which an acousto-optical (AO) area sensor is employed to record the intensity of
      an ultrasound wavefield on a two-dimensional plane. This paper reports on the
      application of acoustography as a simple but practical method for assessing
      transducer field characteristics. A case study performed on a commercial
      transducer is reported, where the radiated fields are imaged using acoustography
      and compared to the corresponding quantities that are predicted numerically.

PMID- 23967015
TI  - Sarcopenia and piscines: the case for indeterminate-growing fish as unique
      genetic model organisms in aging and longevity research.
AB  - Sarcopenia and dynapenia pose significant problems for the aged, especially as
      life expectancy rises in developed countries. Current therapies are marginally
      efficacious at best, and barriers to breakthroughs in treatment may result from
      currently employed model organisms. Here, we argue that the use of indeterminate
      growing teleost fish in skeletal muscle aging research may lead to therapeutic
      advancements not possible with current mammalian models. Evidence from a
      comparative approach utilizing the subfamily Danioninae suggests that the
      indeterminate growth paradigm of many teleosts arises from adult muscle stem
      cells with greater proliferative capacity, even in spite of smaller progenitor
      populations. We hypothesize that paired-box transcription factors, Pax3/7, are
      involved with this enhanced self-renewal and that prolonged expression of these
      factors may allow some fish species to escape, or at least forestall,
      sarcopenia/dynapenia. Future research efforts should focus on the experimental
      validation of these genes as key factors in indeterminate growth, both in the
      context of muscle stem cell proliferation and in prevention of skeletal muscle
      senescence. 

PMID- 23967017
TI  - Prevalence of occult hepatitis B virus in plasma and peripheral blood mononuclear
      cell compartments of patients with chronic hepatitis C infection in tehran-iran.
AB  - BACKGROUND: Occult hepatitis B virus (HBV) infection (OBI) is frequently reported
      in patients with chronic hepatitis C virus (HCV) infection. An association
      between OBI and more liver damage, cirrhosis, hepatocellular carcinoma, and
      reduced response to interferon therapy in patients with HCV infection is
      suggested. OBJECTIVES: The aim of this study was to determine the prevalence of
      occult HBV, and evaluate its clinical influence on patients with chronic HCV.
      PATIENTS AND METHODS: A cohort study including50 patients with positive results
      for HCV, and negative results for HBsAg tests was performed. The patients were
      divided into two groups: one group had positive results for both HCV and occult
      HBV tests (n = 18), and the other had positive results for HCV, but negative
      findings for occult HBV (n = 32). All were treated with PEG-IFN alpha-2a and
      Ribavirin. Presence of HCV RNA was followed in these patients. RESULTS: HBV-DNA
      was detected using nested-PCR in 20% of plasma and 32.6% of peripheral blood
      mononuclear cell (PBMC) compartments. No significant differences were observed
      between patients with and without occult HBV for sex, age, duration of HCV
      infection, histological markers, presence of anti-HBc, HCV viral load, and HCV
      genotype. The response rate was significantly higher in patients with positive
      results for HBV-DNA test compared to those with negative findings (100% vs. 71.9
      %, P < 0.05). CONCLUSIONS: In conclusion, occult HBV was found in 36% of patients
      with negative results for HBsAg, but positive results for HCV. Detection of HBV
      DNA in both PBMCs and plasma together in comparison with plasma alone provided
      more true identification of OBI.The SVR rate was significantly higher in
      coinfected patients than mono-infected ones.

PMID- 23967018
TI  - Methodological and Statistical Comments on CASPIAN-III Study.

PMID- 23967019
TI  - Seroprevalence of anti-hepatitis a antibody among 1 - 15 year old children in
      kashan-iran.
AB  - BACKGROUND: Worldwide, hepatitis A is a common infection during childhood
      especially in developing countries. It can cause severe complications in adults
      and patients with underlying diseases. OBJECTIVES: This study was performed to
      determine the seroprevalence of hepatitis A in 1 - 15 year-old children of
      Kashan. PATIENTS AND METHODS: This cross-sectional study was performed on 666 one
      to fifteen year-old children from health-care centers in Kashan city during 2012.
      Total antibodies against hepatitis A were measured in sera by enzyme-linked
      immunosorbent assay (ELISA). RESULTS: Totally, 3.9% of children were
      seropositive. Mean number of family members was 3.92 +/- 0.89. There was no
      difference in seroprevalence of hepatitis A relative to sex, family size, mean
      age and age groups. CONCLUSIONS: In this city, a great proportion of children are
      susceptible to hepatitis A and it's complications at an older age. This decrease
      in seropositivity may be caused by elevated hygien level. According to our
      results hepatitis A vaccination is recommended at early childhood such as that of
      other regions where low prevalence of hepatitis A infection is found.

PMID- 23967020
TI  - Fibrosis evaluation by transient elastography in patients with long-term
      sustained HCV clearance.
AB  - BACKGROUND: Reversibility of advanced fibrosis after HCV-clearance is an
      important goal of therapy. OBJECTIVES: Measuring liver stiffness (LS) by
      transient elastography (TE) might be helpful in this setting. PATIENTS AND
      METHODS: We evaluated 104 patients with biopsy-proven chronic hepatitis C (CHC)
      and sustained virological response (SVR) after Peg-Interferon (IFN) plus
      ribavirin since at least 18 months. HCV-eradication was confirmed searching for
      serum HCV-RNA (TMA(r) sensitivity > 5-10 IU/ml). Data from literature reported
      the best LS cut-off values for different stages of liver fibrosis were 7.1 kPa
      for Metavir stage 2 (F2), 9.5 kPa for F3 and 12.5 for cirrhosis (F4). RESULTS: TE
      was not reliable in four SVR obese patients. Metavir-stage of biopsy was F0-1 in
      28, F2 in 47, F3 in 17 and F4 in eight patients. The median interval elapsed
      since achieving SVR was 36 months (range: 18-77, SD!!:18). Stratifying patients
      according to the histological stage assessed before treatment, a clear-cut
      gradient of LS values was observed from F0-1: median: 3.8 kPa (range: 3.5-4.9) to
      F2: 4.6 kPa (3.8-6.0), F3: 6.2 kPa (4.8-8.6) and F4: 8.4 kPa (6.2-9.2) (P =
      0.001). Overall, 86 patients had lower values of LS than the expected LS values
      according to Metavir-stage. At multivariate logistic analysis gamma-GT and
      histological steatosis were independently associated with persistence of higher
      values of LS. CONCLUSION: Long term responders to IFN-based therapies have lower
      LS values than those who are untreated and still viraemic. High levels of gamma
      GT and liver steatosis, all markers of insulin resistance, may hamper reduction
      of liver stiffness after HCV-clearance.

PMID- 23967021
TI  - Controversial concepts regarding T helper 1 and T helper 2 cytokines in hepatitis
      C virus infected patients.

PMID- 23967022
TI  - A Simple Noninvasive Score Based on Routine Parameters can Predict Liver
      Cirrhosis in Patients With Chronic Hepatitis C.
AB  - BACKGROUND: Liver biopsy has remained the gold standard for the diagnosis of
      chronic hepatitis C; even though, it has a low but non-negligible rate of both
      false negative and complications. Several authors have proposed noninvasive tools
      to diagnose cirrhosis. But none of them showed complete concordance with liver
      biopsy. OBJECTIVES: To devise a score based on noninvasive routine parameters
      that discriminate between patients with a high risk, and those with a low risk of
      cirrhosis among patients with chronic hepatitis C without performing liver
      biopsy, and to compare this score with other ones using routine parameters
      devoted to this aim. PATIENTS AND METHODS: We reviewed the charts of patients
      with chronic hepatitis C who performed a liver biopsy between 2000 and 2004.
      Multivariate analysis was used to identify independent predictors of cirrhosis.
      An independent group of patients with chronic hepatitis C admitted for a liver
      biopsy between 2007 and 2012 constituted the validation set. RESULTS: We enrolled
      249 patients who had complete laboratoristic data, and sufficient liver tissue
      for fibrosis staging. Age, AST, prothrombin activity, and platelets were
      identified as independent predictors of histological cirrhosis. We categorized
      these variables, and devised a novel score called CISCUN (Cirrhosis Score
      University of Naples), giving one point to each of the following predictors: age
      > 40 years; AST > 2 upper normal values; platelet count < 160.000/mmc;
      prothrombin activity < 100%. Cirrhosis rate was 2.9% for the 103 patients with a
      CISCUN = 0 or 1, 23.4% for the 124 patients with a CISCUN of 2 or 3, and 86.4%
      for the 22 patients with a CISCUN = 4. These results were confirmed in the
      independent validation group of 285 patients with similar characteristics.
      CONCLUSIONS: Patients with chronic hepatitis C and with a CISCUN <= 1 had a very
      low rate of cirrhosis while those with a CISCUN = 4 had a high risk of cirrhosis.
      Patients with CISCUN = 2 or 3 had an intermediate rate of cirrhosis, and
      therefore needed to perform a liver biopsy to receive a reliable diagnosis.

PMID- 23967023
TI  - Activation of Nrf2-Antioxidant Response Element Mediated Glutamate Cysteine
      Ligase Expression in Hepatoma Cell line by Homocysteine.
AB  - BACKGROUND: Homocysteine is a sulfur-containing amino acid which formed (mainly
      in the liver) during the metabolism of methionine. Prior studies indicated the
      important role of hyperhomocysteinemia in pathogenesis and progression of
      alcoholic liver disease, liver steatosis and cirrhosis. One of the most important
      mechanisms by which homocysteine promote the development of hepatic injury is
      oxidative stress. Transcription factor Nrf2-mediated antioxidant response,
      represents critical cellular defense mechanism that serves to maintain
      intracellular redox homeostasis and limit oxidative stress. Glutamate cysteine
      ligase catalytic (GCLc) is rate limiting enzyme in the synthesis of glutathione,
      an important endogenous antioxidant. OBJECTIVES: This study was conducted to
      investigate whether homocysteine induces the Nrf2 dependent expression of GCLc in
      hepatoma cell line (HepG2) and whether this induction is mediated by antioxidant
      response element (ARE) which present within its promoter. MATERIALS AND METHODS:
      Glutathione (GSH) content was measured by flow cytometry. Using electro mobility
      shift assay (EMSA) and western blotting, ARE-binding activity of Nrf2 for GCLc
      was demonstrated. Real time RT-PCR and western blotting were performed to
      evaluate whether homocysteine was able to induce mRNA and protein expression of
      GCL. RESULTS: Exposure of HepG2 cells to 50 uMD/L homocysteine and western
      blotting of nuclear extracts revealed that Nrf2 is strongly stabilized and became
      detectable in nuclear extracts. EMSA demonstrated increased binding of Nrf2 to
      oligomers containing GCL promoter - specific ARE -binding site.A time- dependent
      increase in the gene and protein expression of GCL was observed. Additionally,
      GSH, which is prime scavenger of free radicals in cells, decreased initially.
      Elevation of GSH, following the initial decline, closely correlated with gene
      expression profile of GCLc, which is a rate-limiting enzyme in GSH synthesis.
      CONCLUSIONS: Altogether, we provide direct evidence that homocysteine activates
      Nrf2-mediated antioxidant response, which protects HepG2 cells from oxidative
      damage.

PMID- 23967024
TI  - Some considerations about cardiac toxicity of combination therapy for chronic
      hepatitis C.

PMID- 23967025
TI  - Serum lipoprotein profiles and response to pegylated interferon plus ribavirin
      combination therapy in patients with chronic HCV genotype 1b infection.
AB  - BACKGROUND: Abnormal serum lipid profiles have been noted in patients with
      chronic hepatitis C virus (HCV) infection. Moreover, many reports suggest that
      serum lipoprotein profiles are more profoundly distorted in patients with HCV G1b
      infection who have an unfavorable response to pegylated interferon (peg-IFN) plus
      ribavirin (RBV) combination therapy. However, after the discovery of single
      nucleotide polymorphisms near the IL28B gene (rs8099917 and rs12979860) as potent
      predictive factors affecting the response to peg-IFN plus RBV, lipid factors are
      thought to be confounding factors. OBJECTIVES: To re-examine the significance of
      lipoprotein profiles on virological response to peg-IFN plus RBV combination
      therapy in patients with chronic HCV G1b infection, we examined cholesterol and
      triglyceride concentrations in each lipoprotein fraction separated by high
      performance liquid chromatography. PATIENTS AND METHODS: Lipoprotein profiles
      were examined using fasting sera from 108 patients infected with HCV G1b who had
      chronic hepatitis, as determined by liver biopsy. Results of lipoprotein profiles
      and clinical data, including IL28B genotype and amino acid substitution at aa70
      of HCV G1b, were compared between patients with a sustained virological response
      (SVR) and non-SVR or a non-virological response (NVR) and virological responses
      other than NVR (non-NVR). In addition, significant predictive factors
      independently associated with virological response to peg-IFNalpha-2b plus RBV
      were determined by logistic regression analysis. RESULTS: An increased ratio of
      cholesterol/triglyceride in very low-density lipoprotein (odds ratio (OR) 3.03;
      95% confidence interval (CI) 1.01-9.44) along with a major genotype of rs8099917
      (OR 9.09; 95% CI 2.94-33.33), were independent predictive factors for SVR. In
      contrast, lipid factors were not elucidated as independent predictive factors for
      NVR. CONCLUSIONS: Examination of the fasting lipid profile has clinical
      importance in predicting the efficacy of peg-IFN-alpha-2b plus RBV combination
      therapy for patients with HCV G1b even after the discovery of the IL28 genotype
      as a potent predictive factor.

PMID- 23967026
TI  - The liver Metastatic Adenocarcinoma of Colorectal Cancer With Synchronous
      Isolated Hepatic Tuberculosis.

PMID- 23967027
TI  - Noninvasive localization of accessory pathways in patients with wolff-Parkinson
      white syndrome: a strain imaging study.
AB  - BACKGROUND: Noninvasive techniques for the localization of the accessory pathways
      (APs) might help guide mapping procedures and ablation techniques. We sought to
      examine the diagnostic accuracy of strain imaging for the localization of the APs
      in Wolff-Parkinson-White syndrome. METHODS: We prospectively studied 25 patients
      (mean age = 32 +/- 17 years, 58.3% men) with evidence of pre-excitation on
      electrocardiography (ECG). Electromechanical interval was defined as the time
      difference between the onset of delta wave and the onset of regional myocardial
      contraction. Time differences between the onset of delta wave (delta) and the
      onset of regional myocardial contraction (delta-So), peak systolic motion (delta
      Sm), regional strain (delta-epsilon), peak strain (delta-epsilonp), and peak
      strain rate (delta-SRp) were measured. RESULTS: There was a significant
      difference between time to onset of delta wave to onset of peak systolic motion
      (mean +/- SD) in the AP location (A) and normal segments (B) versus that in the
      normal volunteers (C) [A: (57.08 +/- 23.88 msec) vs. B: (75.20 +/- 14.75) vs. C:
      (72.9 0 +/- 11.16); p value (A vs. B) = 0.004 and p value (A vs. C) = 0.18] and
      [A: (49.17 +/- 35.79) vs. B: (67.60 +/- 14.51) vs. C: (67.40 +/- 6.06 msec); p
      value (A vs. B) < 0.001 and p value (A vs. C) = 0.12, respectively]. CONCLUSION:
      Our study showed that strain imaging parameters [(delta-So) and (delta-Strain)]
      are superior to the ECG in the localization of the APs (84% vs. 76%).

PMID- 23967028
TI  - Can a new antiseptic agent reduce the bacterial colonization rate of central
      venous lines in post-cardiac surgery patients?
AB  - BACKGROUND: Central venous (CV) catheters play an essential role in the
      management of critically ill patients in the Intensive Care Unit (ICU). CV lines
      are, however, allied to catheter-associated blood stream infections. Bacterial
      colonization of CV lines is deemed the main cause of catheter-associated
      infection. The purpose of our study was to compare bacterial colony counts in the
      catheter site before CV line insertion in two groups of post-cardiac surgery
      patients: a group receiving Sanosil (an antiseptic agent composed of H2O2 and
      silver) and a control group. METHODS: This interventional prospective double
      blinded clinical trial recruited the patients in three post-cardiac surgery ICUs
      of a heart center. The participants were divided into interventional (113
      patients) and control (136 patients) groups. Sanosil was added to the routine
      preparation procedure (Chlorhexidine bath one day before and scrub with Povidone
      Iodine just before the CV line insertion). After the removal of the CV lines, the
      catheters tips were sent for culture and evaluation of colony counts. RESULTS:
      Catheter colonization occurred in 55 (22.1%) patients: 26 (23%) patients in the
      Sanosil group and 29 (21.3%) in the control group; there was no significant
      statistical difference between the two groups (p value = 0.75, RR = 1.05, 95% CI:
      0.76-1.45). The most common organism having colonized in the cultures of the
      catheter tips was staphylococcus epidermis: 20 cases in the control group and 16
      cases in the intervention group. CONCLUSION: Catheter colonization frequently
      occurs in post-cardiac surgery patients. However, our results did not indicate
      the effectiveness of adding Sanosil to the routine preparation procedure with
      respect to reducing catheter bacterial colonization.

PMID- 23967029
TI  - Coronary arteries bypass grafting surgery in elderly patients.
AB  - BACKGROUND: The incidence of coronary artery bypass grafting surgery (CABG) in
      elderly patients has been increasing. There are contradictory reports on the
      early outcome of elderly coronary artery patients as compared with their young
      counterparts. We designed this retrospective study to address this issue.
      METHODS: We retrospectively analyzed the results of 1489 on-pump CABG cases
      performed at our hospital during a 4.5-year period. Perioperative data such as
      demographic, medical, clinical, operative, and postoperative variables were
      collected and compared between patients 70 years old or younger (Group A, n =
      1164) and patients above 70 years of age (Group B, n = 325). Statistical analysis
      was performed using the t-test for the continuous and the X(2) tests for the
      categorical variables. Significant variables according to the univariate analysis
      (X(2) and t-test) were further analyzed using multivariate logistic regression
      analysis. RESULTS: The variables of weight (P value < 0.001), preoperative PO2 (P
      value = 0.005), ejection fraction > 30% (P value = 0.001), body surface area (P
      value = 0.003), and hypercholesterolemia (P value = 0.007) were higher in Group
      A, whereas preoperative myocardial infarction (P value < 0.001), postoperative
      low cardiac output syndrome (P value = 0.019), emergent surgery (P value =
      0.003), inotropic drug use (P value < 0.001), preoperative heparin use (P value <
      0.001), re-exploration for bleeding (P value = 0.015), hospital stay (P value <
      0.001), low ejection fraction (<= 30%) (P value = 0.001), preoperative creatinine
      > 1.5 mg/dl (P value < 0.001), chronic obstructive pulmonary disease (P value <
      0.001), intra-aortic balloon pump use (P value < 0.001), infection (P value <
      0.001), pulmonary complications (P value < 0.001), atrial fibrillation (P value <
      0.001), postoperative renal complications (P value < 0.001), and death (P value =
      0.012) were more frequent in Group B. CONCLUSION: CABG in the elderly patients
      had certain surgical risks such as chronic obstructive pulmonary disease,
      preoperative myocardial infarction, emergent surgery, and death. Also,
      postoperative complications such as pulmonary complications, inotropic drug use,
      intra-aortic balloon pump use, and infection were more frequent in the elderly
      than in the younger patients.

PMID- 23967030
TI  - Angiotensin- converting enzyme insertion/deletion polymorphism and its
      association with coronary artery disease in an Iranian population.
AB  - BACKGROUND: The study of the association between genotype and phenotype is of
      great importance for the prediction of many diseases and pathophysiological
      conditions. The relationship between angiotensin-converting enzyme (ACE) gene
      insertion/ deletion (I/D) polymorphism and pathological processes such as
      coronary artery disease (CAD) has been investigated previously with discordant
      results. This study was designed to determine the association between ACE gene
      I/D polymorphism and CAD in an Iranian population. METHODS: A total of 1050
      individuals who were referred to Tehran Heart Center for coronary angiography
      were recruited. Six hundred seventy-six CAD-positive patients (documented by
      coronary angiography and Gensini scores higher than 6) and 374 CAD-negative
      patients were evaluated for ACE gene I/D polymorphism via the Polymerase Chain
      Reaction Amplification method. The patients' age, sex, smoking status and its
      duration as well as familial history of CAD, hypertension, and diabetes mellitus
      were recorded. RESULTS: Five hundred four (74.6%) of the CAD-positive patients
      were male, and the mean age of this group was 60 (60 +/- 10). In the CAD-negative
      individuals, the mean age was 56 (56 +/- 10) and 196 of them were male (52.4%).
      After the analysis of all the groups and gender subgroups, neither genotype nor
      allele frequency was significantly different between the CAD-positive and CAD
      negative groups (p values for genotypes and allele frequencies were 0.494 and
      0.397, respectively). CONCLUSION: ACE gene I/D polymorphism was not associated
      with an increased risk of CAD in an Iranian population.

PMID- 23967031
TI  - Comparison of Echocardiographic Markers of Cardiac Dyssynchrony and Latest Left
      Ventricular Activation Site in Heart Failure Patients with and without Left
      Bundle Branch Block.
AB  - BACKGROUND: Several echocardiographic markers have been introduced to assess the
      left ventricular (LV) mechanical dyssynchrony. We studied dyssynchrony markers
      and the latest LV activation site in heart failure patients with and without left
      bundle branch block (LBBB). METHODS: Conventional echocardiography and tissue
      velocity imaging were performed for 78 patients (LV ejection fraction <= 35%),
      who were divided into two groups: LBBB (n = 37) and non-LBBB (n = 41). Time-to
      peak systolic velocity (Ts) was measured in 12 LV segments in the mid and basal
      levels. Seven dyssynchrony markers were defined: delay and standard deviation
      (SD) of Ts in all and basal segments, septal-lateral and anteroseptal-posterior
      wall delay (at the basal level), and interventricular mechanical delay (IVMD).
      RESULTS: The LBBB patients had significantly higher QRS duration and IVMD. The
      posterior wall was the latest activated site in the LBBB and the inferior wall
      was the latest in the non-LBBB patients. The most common dyssynchrony marker in
      the LBBB group was the SD of Ts in all segments (73%), whereas it was Ts delay in
      the basal segments in the non-LBBB group (48.8%). Ts delay and SD of all LV
      segments, septal lateral delay, septal-to-posterior wall delay by M-mode, pre
      ejection period of the aortic valve, and IVMD were significantly higher in the
      LBBB group than in the non-LBBB group. Also, 29.3% of the non-LBBB and 10.8% of
      the LBBB patients did not show dyssynchrony by any marker. The number of patients
      showing dyssynchrony by >= 3 markers was remarkably higher in the LBBB patients
      (73% vs. 43.9%, respectively; p value = 0.044). CONCLUSION: The LBBB patients
      presented with a higher prevalence of dyssynchrony according to the frequently
      used echocardiographic markers. The latest activation site was different between
      the groups.

PMID- 23967032
TI  - Evaluation of cardiovascular diseases and their risk factors in hospitalized
      patients in East azerbaijan province, northwest iran: a review of 18323 cases.
AB  - BACKGROUND: Coronary artery disease (CAD) is accountable for more than 30% of
      deaths worldwide and is, thus, deemed the most important factor in terms of
      disease burden around the globe. This study aimed to evaluate CAD and its risk
      factors in hospitalized patients in the East Azerbaijan Province, northwest Iran,
      from 2006 to 2007. METHODS: Data on 18.323 patients hospitalized due to
      cardiovascular diseases were collected to evaluate the diseases and their risk
      factors in 15 hospitals in the East Azerbaijan Province, northwest Iran. We
      assessed the main diagnosis of cardiovascular disease on admission in each
      hospital. Also, types of interventional and surgical procedures were assessed and
      all these variables were compared between men and women. RESULTS: The study
      population consisted of 56.6% male and 43.4% female patients. The median and
      range between quartile 1 and 3 (Q1-Q3) ages of the males and females were 59 (49
      70) and 62 (51-71) years, respectively. Ischemic heart diseases were diagnosed in
      68.4%, electrophysiological disorders in 6.5%, and valvular heart diseases in
      4.5% of the patients. The frequencies of the studied risk factors were as
      follows: cigarette smoking (47.5%); hypertension (66.95%); diabetes mellitus
      (35.9%); and history of cerebrovascular accident (16.4%) and renal disease
      (13.4%). Medical therapy was performed in 79.23%, surgery in 6.28%, and
      cardiovascular interventional therapy in 13.99% of the patients. The in-hospital
      mortality rate was 1.57% (1.42% in the males and 1.76% in the females; p value =
      0.009). CONCLUSION: The most frequent known risk factors in the hospitalized
      patients were smoking, alcohol consumption, and diabetes. In the northwest of
      Iran, age at hospitalization due to cardiovascular diseases is slightly lower
      than that in the Western populations; however, sex distribution, diagnoses, and
      treatment modalities are not significantly different from those reported in
      Western countries.

PMID- 23967033
TI  - Hemi-fontan or bidirectional cavopulmonary shunt for right ventricular failure
      after mitral valve replacement and acute ascending aortic dissection: report of
      two cases.
AB  - Right ventricular failure due to right coronary artery disease, right ventricular
      hypertrophy, stunning, abnormal septal motion, myocardial infarction, or non
      homogeneous distribution of cardioplegia is an uncommon but serious complication
      of open heart surgery. We report a patient with severe right ventricular
      hypertrophy secondary to severe mitral valve stenosis and another patient with
      detachment of the right coronary artery due to the dissection of the ascending
      aorta. The patients developed right ventricular failure, which persisted after
      surgery and rendered weaning from cardiopulmonary bypass unsuccessful. Through a
      hemi-Fontan, or bidirectional cavopulmonary shunt, and an intra-aortic balloon
      pump, the patients were successfully weaned from cardiopulmonary bypass. This
      shunt may be an alternative to a right ventricular assist device in some patients
      with right ventricular failure. The long-term outcome and the indication of bi
      directional cavopulmonary shunt has not been confirmed, although it is believed
      to be effective for saving the life of patients with low cardiac output and acute
      right ventricular failure. In our cases, six months following the operation,
      there was some degree of recovery of the right ventricular function. In long-term
      follow-up, however, it would be interesting for the authors to know if the
      improved right ventricular function, with better antegrade pulsatile flow in the
      pulmonary artery, in any way interferes with the functioning of the bidirectional
      cavopulmonary shunt. 

PMID- 23967034
TI  - Radiofrequency ablation of accessory pathways in children with complex congenital
      cardiac lesions: a report of three cases.
AB  - Catheter ablation is an accepted, highly effective modality of treatment for
      cardiac arrhythmias in children. The success rate depends on the operator's
      experience, especially in cases involving complex anatomies. We hereby report our
      recent experience of successful ablation of accessory pathways in three children
      with complex congenital heart diseases. The first case was a 7-year-old girl with
      tricuspid atresia and a previous Glenn shunt, in whom a sub-epicardial overt
      accessory pathway was successfully ablated via the coronary sinus. The second
      case, a 9-year-old girl, received accessory pathway ablation via the fenestration
      of an extracardiac Fontan pathway. The third case was a 14-year-old boy with
      dextrocardia, common atrium, common ventricle, and a previous extracardiac Fontan
      operation, in whom ablation of a concealed accessory pathway was carried out
      retrogradely from the aorta. All the ablations were done in Rajaie
      Cardiovascular, Medical and Research Center, Tehran, and all the patients were
      discharged from the hospital without any complication. 

PMID- 23967035
TI  - Endovascular treatment of isolated bilateral internal iliac artery aneurysms with
      a branched endograft: a case report.
AB  - Isolated bilateral internal iliac artery (IIA) aneurysm is a rare and potentially
      lethal disease. Endovascular repair of this disorder is a matter of debate. A
      symptomatic 68-year-old male presented with severe pelvic pains. Computed
      tomography revealed a leaking 46-mm aneurysm in the right IIA, a 27-mm aneurysm
      in the left IIA, and ectatic changes at a diameter of 31 mm in the right common
      iliac artery (CIA). Due to lower rates of morbidity and mortality, an
      endovascular approach was chosen instead of open surgical repair. However, due to
      anatomical constraints, an endograft had to be implanted in a healthy aorta in
      order to support an iliac branch endograft in the left CIA. Subsequently,
      following coil embolization of the left IIA, an iliac stent graft was extended to
      the right external iliac artery (EIA). Two-year follow-up CT imaging showed
      complete exclusion of all the aneurysms and patency of the pelvic visceral
      arteries. The patient is currently asymptomatic. Endovascular repair of bilateral
      isolated IIAs can be a feasible treatment option. However, due to limited
      availability of sizes in iliac branch devices currently on the market, a main
      body device is sometimes required to be deployed in a healthy aorta for
      additional endograft support. 

PMID- 23967036
TI  - Localized Treatment of Chest Pain is Still Common in Rural Areas.

PMID- 23967037
TI  - Quantum attack-resistent certificateless multi-receiver signcryption scheme.
AB  - The existing certificateless signcryption schemes were designed mainly based on
      the traditional public key cryptography, in which the security relies on the hard
      problems, such as factor decomposition and discrete logarithm. However, these
      problems will be easily solved by the quantum computing. So the existing
      certificateless signcryption schemes are vulnerable to the quantum attack.
      Multivariate public key cryptography (MPKC), which can resist the quantum attack,
      is one of the alternative solutions to guarantee the security of communications
      in the post-quantum age. Motivated by these concerns, we proposed a new
      construction of the certificateless multi-receiver signcryption scheme (CLMSC)
      based on MPKC. The new scheme inherits the security of MPKC, which can withstand
      the quantum attack. Multivariate quadratic polynomial operations, which have
      lower computation complexity than bilinear pairing operations, are employed in
      signcrypting a message for a certain number of receivers in our scheme. Security
      analysis shows that our scheme is a secure MPKC-based scheme. We proved its
      security under the hardness of the Multivariate Quadratic (MQ) problem and its
      unforgeability under the Isomorphism of Polynomials (IP) assumption in the random
      oracle model. The analysis results show that our scheme also has the security
      properties of non-repudiation, perfect forward secrecy, perfect backward secrecy
      and public verifiability. Compared with the existing schemes in terms of
      computation complexity and ciphertext length, our scheme is more efficient, which
      makes it suitable for terminals with low computation capacity like smart cards.

PMID- 23967038
TI  - High and distinct range-edge genetic diversity despite local bottlenecks.
AB  - The genetic consequences of living on the edge of distributional ranges have been
      the subject of a largely unresolved debate. Populations occurring along
      persistent low latitude ranges (rear-edge) are expected to retain high and unique
      genetic diversity. In contrast, currently less favourable environmental
      conditions limiting population size at such range-edges may have caused genetic
      erosion that prevails over past historical effects, with potential consequences
      on reducing future adaptive capacity. The present study provides an empirical
      test of whether population declines towards a peripheral range might be reflected
      on decreasing diversity and increasing population isolation and differentiation.
      We compare population genetic differentiation and diversity with trends in
      abundance along a latitudinal gradient towards the peripheral distribution range
      of Saccorhiza polyschides, a large brown seaweed that is the main structural
      species of kelp forests in SW Europe. Signatures of recent bottleneck events were
      also evaluated to determine whether the recently recorded distributional shifts
      had a negative influence on effective population size. Our findings show
      decreasing population density and increasing spatial fragmentation and local
      extinctions towards the southern edge. Genetic data revealed two well supported
      groups with a central contact zone. As predicted, higher differentiation and
      signs of bottlenecks were found at the southern edge region. However, a decrease
      in genetic diversity associated with this pattern was not verified. Surprisingly,
      genetic diversity increased towards the edge despite bottlenecks and much lower
      densities, suggesting that extinctions and recolonizations have not strongly
      reduced diversity or that diversity might have been even higher there in the
      past, a process of shifting genetic baselines.

PMID- 23967046
TI  - The relationship between media consumption and health-related anxieties after the
      Fukushima Daiichi nuclear disaster.
AB  - BACKGROUND: The Fukushima Daiichi nuclear disaster caused a global panic by a
      release of harmful radionuclides. In a disaster setting, misusage of contemporary
      media sources available today can lead to disseminated incorrect information and
      panic. The study aims to build a scale which examines associations between media
      and individual anxieties, and to propose effective media usages for future
      disaster management. METHODS: The University of Tokyo collaborated with the
      Fukushima local government to conduct a radiation-health-seminar for a total of
      1560 residents, at 12 different locations in Fukushima. A 13 item questionnaire
      collected once before and after a radiation-seminar was used on factor analysis
      to develop sub-scales for multiple regression models, to determine relationships
      between the sub-scales and media type consumed. A paired t-test was used to
      examine any changes in sub-scale of pre- and post-seminar scores. RESULTS: Three
      sub-scales were revealed and were associated with different media types: was with
      rumors, while concern for the future was positively associated with regional
      newspapers and negatively with national-newspapers. Anxiety about social
      disruption was associated with radio. The seminar had a significant effect on
      anxiety reduction for all the three sub-scales. CONCLUSION: Different media types
      were associated with various heightened concerns, and that a radiation seminar
      was helpful to reduce anxieties in the post-disaster setting. By tailoring post
      disaster messages via specific media types, i.e., radio, it may be possible to
      effectively convey important information, as well as to calm fears about
      particular elements of post-disaster recovery and to combat rumors.

PMID- 23967047
TI  - Intron retention in mRNA encoding ancillary subunit of insect voltage-gated
      sodium channel modulates channel expression, gating regulation and drug
      sensitivity.
AB  - Insect voltage-gated sodium (Nav) channels are formed by a well-known pore
      forming alpha-subunit encoded by para-like gene and ancillary subunits related to
      TipE from the mutation "temperature-induced-paralysis locus E." The role of these
      ancillary subunits in the modulation of biophysical and pharmacological
      properties of Na(+) currents are not enough documented. The unique neuronal
      ancillary subunit TipE-homologous protein 1 of Drosophila melanogaster (DmTEH1)
      strongly enhances the expression of insect Nav channels when heterologously
      expressed in Xenopus oocytes. Here we report the cloning and functional
      expression of two neuronal DmTEH1-homologs of the cockroach, Periplaneta
      americana, PaTEH1A and PaTEH1B, encoded by a single bicistronic gene. In PaTEH1B,
      the second exon encoding the last 11-amino-acid residues of PaTEH1A is shifted to
      3'UTR by the retention of a 96-bp intron-containing coding-message, thus
      generating a new C-terminal end. We investigated the gating and pharmacological
      properties of the Drosophila Nav channel variant (DmNav1-1) co-expressed with
      DmTEH1, PaTEH1A, PaTEH1B or a truncated mutant PaTEH1Delta(270-280) in Xenopus
      oocytes. PaTEH1B caused a 2.2-fold current density decrease, concomitant with an
      equivalent alpha-subunit incorporation decrease in the plasma membrane, compared
      to PaTEH1A and PaTEH1Delta(270-280). PaTEH1B positively shifted the voltage
      dependences of activation and slow inactivation of DmNav1-1 channels to more
      positive potentials compared to PaTEH1A, suggesting that the C-terminal end of
      both proteins may influence the function of the voltage-sensor and the pore of
      Nav channel. Interestingly, our findings showed that the sensitivity of DmNav1-1
      channels to lidocaine and to the pyrazoline-type insecticide metabolite DCJW
      depends on associated TEH1-like subunits. In conclusion, our work demonstrates
      for the first time that density, gating and pharmacological properties of Nav
      channels expressed in Xenopus oocytes can be modulated by an intron retention
      process in the transcription of the neuronal TEH1-like ancillary subunits of P.
      americana. 

PMID- 23967048
TI  - The high burden of tuberculosis (TB) and human immunodeficiency virus (HIV) in a
      large Zambian prison: a public health alert.
AB  - BACKGROUND: Tuberculosis (TB) and human immunodeficiency virus (HIV) represent
      two of the greatest health threats in African prisons. In 2010, collaboration
      between the Centre for Infectious Disease Research in Zambia, the Zambia Prisons
      Service, and the National TB Program established a TB and HIV screening program
      in six Zambian prisons. We report data on the prevalence of TB and HIV in one of
      the largest facilities: Lusaka Central Prison. METHODS: Between November 2010 and
      April 2011, we assessed the prevalence of TB and HIV amongst inmates entering,
      residing, and exiting the prison, as well as in the surrounding community. The
      screening protocol included complete history and physical exam, digital
      radiography, opt-out HIV counseling and testing, sputum smear and culture. A TB
      case was defined as either bacteriologically confirmed or clinically diagnosed.
      RESULTS: A total of 2323 participants completed screening. A majority (88%) were
      male, median age 31 years and body mass index 21.9. TB symptoms were found in
      1430 (62%). TB was diagnosed in 176 (7.6%) individuals and 52 people were already
      on TB treatment at time of screening. TB was bacteriologically confirmed in 88
      cases (3.8%) and clinically diagnosed in 88 cases (3.8%). Confirmed TB at entry
      and exit interventions were 4.6% and 5.3% respectively. Smear was positive in
      only 25% (n = 22) of bacteriologically confirmed cases. HIV prevalence among
      inmates currently residing in prison was 27.4%. CONCLUSION: Ineffective TB and
      HIV screening programs deter successful disease control strategies in prison
      facilities and their surrounding communities. We found rates of TB and HIV in
      Lusaka Central Prison that are substantially higher than the Zambian average,
      with a trend towards concentration and potential transmission of both diseases
      within the facility and to the general population. Investment in institutional
      and criminal justice reform as well as prison-specific health systems is urgently
      required.

PMID- 23967049
TI  - A simple approach for COnsumption and RElease (CORE) analysis of metabolic
      activity in single mammalian embryos.
AB  - Non-invasive assay of the consumption and release of metabolites by individual
      human embryos could allow selection at the cleavage stage of development and
      facilitate Single Embryo Transfer in clinical IVF but will require simple, high
      throughput, sensitive methods applicable to small volume samples. A rapid,
      simple, non-invasive method has therefore been devised using a standard
      fluorescence plate reader, and used to measure the consumption of pyruvate and
      glucose, and release of lactate by single bovine embryos at all stages of
      preimplantation development in culture; amino acid profiles have been determined
      using HPLC. Early embryos with an 'intermediate' level (6.14+/-0.27
      pmol/embryo/h) of pyruvate uptake were associated with the highest rate (68.3%)
      of blastocyst development indicating that a mid "optimum" range of pyruvate
      consumption correlates with high viability in this bovine model. 

PMID- 23967050
TI  - Cellular trafficking of thymosin beta-4 in HEPG2 cells following serum
      starvation.
AB  - Thymosin beta-4 (Tbeta4) is an ubiquitous multi-functional regenerative peptide,
      related to many critical biological processes, with a dynamic and flexible
      conformation which may influence its functions and its subcellular distribution.
      For these reasons, the intracellular localization and trafficking of Tbeta4 is
      still not completely defined and is still under investigation in in vivo as well
      as in vitro studies. In the current study we used HepG2 cells, a human hepatoma
      cell line; cells growing in normal conditions with fetal bovine serum expressed
      high levels of Tbeta4, restricted to the cytoplasm until 72 h. At 84 h, a diffuse
      Tbeta4 cytoplasmic immunostaining shifted to a focal perinuclear and nuclear
      reactivity. In the absence of serum, nuclear reactivity was localized in small
      granules, evenly dispersed throughout the entire nuclear envelop, and was
      observed as earlier as at 48 h. Cytoplasmic immunostaining for Tbeta4 in HepG2
      cells under starvation appeared significantly lower at 48 h and decreased
      progressively at 72 and at 84 h. At these time points, the decrease in
      cytoplasmic staining was associated with a progressive increase in nuclear
      reactivity, suggesting a possible translocation of the peptide from the cytoplasm
      to the nuclear membrane. The normal immunocytochemical pattern was restored when
      culture cells submitted to starvation for 84 h received a new complete medium for
      48 h. Mass spectrometry analysis, performed on the nuclear and cytosolic
      fractions of HepG2 growing with and without serum, showed that Tbeta4 was
      detectable only in the cytosolic and not in the intranuclear fraction. These data
      suggest that Tbeta4 is able to translocate from different cytoplasmic domains to
      the nuclear membrane and back, based on different stress conditions within the
      cell. The punctuate pattern of nuclear Tbeta4 immunostaining associated with
      Tbeta4 absence in the nucleoplasm suggest that this peptide might be localized in
      the nuclear pores, where it could regulate the pore permeability. 

PMID- 23967051
TI  - Ovarian cancer stem cells are enriched in side population and aldehyde
      dehydrogenase bright overlapping population.
AB  - Cancer stem-like cells (CSCs)/cancer-initiaiting cells (CICs) are defined as a
      small population of cancer cells that have self-renewal capacity, differentiation
      potential and high tumor-initiating ability. CSCs/CICs of ovarian cancer have
      been isolated by side population (SP) analysis, ALDEFLUOR assay and using cell
      surface markers. However, these approaches are not definitive markers for
      CSCs/CICs, and it is necessary to refine recent methods for identifying more
      highly purified CSCs/CICs. In this study, we analyzed SP cells and aldehyde
      dehydrogenese bright (ALDH(Br)) cells from ovarian cancer cells. Both SP cells
      and ALDH(Br) cells exhibited higher tumor-initiating ability and higher
      expression level of a stem cell marker, sex determining region Y-box 2 (SOX2),
      than those of main population (MP) cells and ALDH(Low) cells, respectively. We
      analyzed an SP and ALDH(Br) overlapping population (SP/ALDH(Br)), and the
      SP/ALDH(Br) population exhibited higher tumor-initiating ability than that of SP
      cells or ALDH(Br) cells, enabling initiation of tumor with as few as 10(2) cells.
      Furthermore, SP/ADLH(Br) population showed higher sphere-forming ability,
      cisplatin resistance, adipocyte differentiation ability and expression of SOX2
      than those of SP/ALDH(Low), MP/ALDH(Br) and MP/ALDH(Low) cells. Gene knockdown of
      SOX2 suppressed the tumor-initiation of ovarian cancer cells. An SP/ALDH(Br)
      population was detected in several gynecological cancer cells with ratios of 0.1%
      for HEC-1 endometrioid adenocarcinoma cells to 1% for MCAS ovary mucinous
      adenocarcinoma cells. Taken together, use of the SP and ALDH(Br) overlapping
      population is a promising approach to isolate highly purified CSCs/CICs and SOX2
      might be a novel functional marker for ovarian CSCs/CICs. 

PMID- 23967052
TI  - 2-methoxyestradiol induces mitotic arrest, apoptosis, and synergistic
      cytotoxicity with arsenic trioxide in human urothelial carcinoma cells.
AB  - 2-Methoxyestradiol (2-ME), an endogenous derivative of 17beta-estradiol, has been
      reported to elicit antiproliferative responses in various tumors. In this study,
      we investigated the effects of 2-ME on cell viability, proliferation, cell cycle,
      and apoptosis in human urothelial carcinoma (UC) cell lines. We used two high
      grade human bladder UC cell lines (NTUB1 and T24). After treatment with 2-ME, the
      cell viability and apoptosis were measured by MTT assay and flow cytometry
      (fluorescence-activated cell sorting), with annexin V-FITC staining and propidium
      iodide (PI) labeling. DNA fragmentation was analyzed by agarose gel
      electrophoresis. Flow cytometry with PI labeling was used for the cell cycle
      analyses. The protein levels of caspase activations, poly (ADP-ribose) polymerase
      (PARP) cleavage, phospho-histone H2A.X, phospho-Bad, and cell cycle regulatory
      molecules were measured by Western blot. The effects of the drug combinations
      were analyzed using the computer software, CalcuSyn. We demonstrated that 2-ME
      effectively induces dose-dependent cytotoxicity and apoptosis in human UC cells
      after 24 h exposure. DNA fragmentation, PARP cleavage, and caspase-3, 7, 8, 9
      activations can be observed with 2-ME-induced apoptosis. The decreased phospho
      Bad (Ser136 and Ser155) and mitotic arrest of the cell cycle in the process of
      apoptosis after 2-ME treatment was remarkable. In response to mitotic arrest, the
      mitotic forms of cdc25C, phospho-cdc2, cyclin B1, and phospho-histone H3 (Ser10)
      were activated. In combination with arsenic trioxide (As2O3), 2-ME elicited
      synergistic cytotoxicity (combination index <1) in UC cells. We concluded that 2
      ME significantly induces apoptosis through decreased phospho-Bad and arrests
      bladder UC cells at the mitotic phase. The synergistic antitumor effect with
      As2O3 provides a novel implication in clinical treatment of UC. 

PMID- 23967053
TI  - To supplement or not to supplement: a metabolic network framework for human
      nutritional supplements.
AB  - Flux balance analysis and constraint based modeling have been successfully used
      in the past to elucidate the metabolism of single cellular organisms. However,
      limited work has been done with multicellular organisms and even less with
      humans. The focus of this paper is to present a novel use of this technique by
      investigating human nutrition, a challenging field of study. Specifically, we
      present a steady state constraint based model of skeletal muscle tissue to
      investigate amino acid supplementation's effect on protein synthesis. We
      implement several in silico supplementation strategies to study whether amino
      acid supplementation might be beneficial for increasing muscle contractile
      protein synthesis. Concurrent with published data on amino acid supplementation's
      effect on protein synthesis in a post resistance exercise state, our results
      suggest that increasing bioavailability of methionine, arginine, and the branched
      chain amino acids can increase the flux of contractile protein synthesis. The
      study also suggests that a common commercial supplement, glutamine, is not an
      effective supplement in the context of increasing protein synthesis and thus,
      muscle mass. Similar to any study in a model organism, the computational modeling
      of this research has some limitations. Thus, this paper introduces the prospect
      of using systems biology as a framework to formally investigate how
      supplementation and nutrition can affect human metabolism and physiology. 

PMID- 23967054
TI  - Mathematical model of bursting in dissociated purkinje neurons.
AB  - In vitro, Purkinje cell behaviour is sometimes studied in a dissociated soma
      preparation in which the dendritic projection has been cleaved. A fraction of
      these dissociated somas spontaneously burst. The mechanism of this bursting is
      incompletely understood. We have constructed a biophysical Purkinje soma model,
      guided and constrained by experimental reports in the literature, that can
      replicate the somatically driven bursting pattern and which hypothesises
      Persistent Na(+) current (INaP) to be its burst initiator and SK K(+) current
      (ISK) to be its burst terminator. 

PMID- 23967055
TI  - Intracellular reprogramming of expression, glycosylation, and function of a plant
      derived antiviral therapeutic monoclonal antibody.
AB  - Plant genetic engineering, which has led to the production of plant-derived
      monoclonal antibodies (mAb(P)s), provides a safe and economically effective
      alternative to conventional antibody expression methods. In this study, the
      expression levels and biological properties of the anti-rabies virus mAb(P) SO57
      with or without an endoplasmic reticulum (ER)-retention peptide signal (Lys-Asp
      Glu-Leu; KDEL) in transgenic tobacco plants (Nicotiana tabacum) were analyzed.
      The expression levels of mAb(P) SO57 with KDEL (mAb(P)K) were significantly
      higher than those of mAb(P) SO57 without KDEL (mAb(P)) regardless of the
      transcription level. The Fc domains of both purified mAb(P) and mAb(P)K and
      hybridoma-derived mAb (mAb(H)) had similar levels of binding activity to the
      FcgammaRI receptor (CD64). The mAb(P)K had glycan profiles of both oligomannose
      (OM) type (91.7%) and Golgi type (8.3%), whereas the mAb(P) had mainly Golgi type
      glycans (96.8%) similar to those seen with mAb(H). Confocal analysis showed that
      the mAb(P)K was co-localized to ER-tracker signal and cellular areas surrounding
      the nucleus indicating accumulation of the mAb(P) with KDEL in the ER. Both
      mAb(P) and mAb(P)K disappeared with similar trends to mAb(H) in BALB/c mice. In
      addition, mAb(P)K was as effective as mAb(H) at neutralizing the activity of the
      rabies virus CVS-11. These results suggest that the ER localization of the
      recombinant mAb(P) by KDEL reprograms OM glycosylation and enhances the
      production of the functional antivirus therapeutic antibody in the plant. 

PMID- 23967057
TI  - Degradation of oxo-biodegradable plastic by Pleurotus ostreatus.
AB  - Growing concerns regarding the impact of the accumulation of plastic waste over
      several decades on the environmental have led to the development of biodegradable
      plastic. These plastics can be degraded by microorganisms and absorbed by the
      environment and are therefore gaining public support as a possible alternative to
      petroleum-derived plastics. Among the developed biodegradable plastics, oxo
      biodegradable polymers have been used to produce plastic bags. Exposure of this
      waste plastic to ultraviolet light (UV) or heat can lead to breakage of the
      polymer chains in the plastic, and the resulting compounds are easily degraded by
      microorganisms. However, few studies have characterized the microbial degradation
      of oxo-biodegradable plastics. In this study, we tested the capability of
      Pleurotus ostreatus to degrade oxo-biodegradable (D2W) plastic without prior
      physical treatment, such as exposure to UV or thermal heating. After 45 d of
      incubation in substrate-containing plastic bags, the oxo-biodegradable plastic,
      which is commonly used in supermarkets, developed cracks and small holes in the
      plastic surface as a result of the formation of hydroxyl groups and carbon-oxygen
      bonds. These alterations may be due to laccase activity. Furthermore, we observed
      the degradation of the dye found in these bags as well as mushroom formation.
      Thus, P. ostreatus degrades oxo-biodegradable plastics and produces mushrooms
      using this plastic as substrate. 

PMID- 23967056
TI  - Deep tissue injury in development of pressure ulcers: a decrease of inflammasome
      activation and changes in human skin morphology in response to aging and
      mechanical load.
AB  - Molecular mechanisms leading to pressure ulcer development are scarce in spite of
      high mortality of patients. Development of pressure ulcers that is initially
      observed as deep tissue injury is multifactorial. We postulate that biomechanical
      forces and inflammasome activation, together with ischemia and aging, may play a
      role in pressure ulcer development. To test this we used a newly-developed bio
      mechanical model in which ischemic young and aged human skin was subjected to a
      constant physiological compressive stress (load) of 300 kPa (determined by
      pressure plate analyses of a person in a reclining position) for 0.5-4 hours.
      Collagen orientation was assessed using polarized light, whereas inflammasome
      proteins were quantified by immunoblotting. Loaded skin showed marked changes in
      morphology and NLRP3 inflammasome protein expression. Sub-epidermal separations
      and altered orientation of collagen fibers were observed in aged skin at earlier
      time points. Aged skin showed significant decreases in the levels of NLRP3
      inflammasome proteins. Loading did not alter NLRP3 inflammasome proteins
      expression in aged skin, whereas it significantly increased their levels in young
      skin. We conclude that aging contributes to rapid morphological changes and
      decrease in inflammasome proteins in response to tissue damage, suggesting that a
      decline in the innate inflammatory response in elderly skin could contribute to
      pressure ulcer pathogenesis. Observed morphological changes suggest that tissue
      damage upon loading may not be entirely preventable. Furthermore, newly developed
      model described here may be very useful in understanding the mechanisms of deep
      tissue injury that may lead towards development of pressure ulcers. 

PMID- 23967058
TI  - Intracellular survival and persistence of Chlamydia muridarum is determined by
      macrophage polarization.
AB  - Macrophages can display a number of distinct phenotypes, known collectively as
      polarized macrophages. The best defined of these phenotypes are the classically
      activated, interferon gamma (IFNgamma)/LPS induced (M1) and alternatively
      activated, IL-4 induced (M2) macrophages. The goal of this study is to
      characterize macrophage-Chlamydia interactions in the context of macrophage
      polarization. Here we use Chlamydia muridarum and murine bone-marrow derived
      macrophages to show Chlamydia does not induce M2 polarization in macrophages as a
      survival strategy. Unexpectedly, the infection of macrophages was silent with no
      upregulation of M1 macrophage-associated genes. We further demonstrate that
      macrophages polarized prior to infection have a differential capacity to control
      Chlamydia. M1 macrophages harbor up to 40-fold lower inclusion forming units
      (IFU) than non-polarized or M2 polarized macrophages. Gene expression analysis
      showed an increase in 16sRNA in M2 macrophages with no change in M1 macrophages.
      Suppressed Chlamydia growth in M1 macrophages correlated with the induction of a
      bacterial gene expression profile typical of persistence as evident by increased
      Euo expression and decreased Omp1 and Tal expression. Observations of permissive
      Chlamydia growth in non-polarized and M2 macrophages and persistence in M1
      macrophages were supported through electron microscopy. This work supports the
      importance of IFNgamma in the innate immune response to Chlamydia. However,
      demonstration that the M1 macrophages, despite an antimicrobial signature, fail
      to eliminate intracellular Chlamydia supports the notion that host-pathogen co
      evolution has yielded a pathogen that can evade cellular defenses against this
      pathogen, and persist for prolonged periods of time in the host. 

PMID- 23967059
TI  - Child Behavior Checklist-Mania Scale (CBCL-MS): development and evaluation of a
      population-based screening scale for bipolar disorder.
AB  - CONTEXT: Early identification of Bipolar Disorder (BD) remains poor despite the
      high levels of disability associated with the disorder. OBJECTIVE: We developed
      and evaluated a new DSM orientated scale for the identification of young people
      at risk for BD based on the Child Behavior Checklist (CBCL) and compared its
      performance against the CBCL-Pediatric Bipolar Disorder (CBCL-PBD) and the CBCL
      Externalizing Scale, the two most widely used scales. METHODS: The new scale,
      CBCL-Mania Scale (CBCL-MS), comprises 19 CBCL items that directly correspond to
      operational criteria for mania. We tested the reliability, longitudinal stability
      and diagnostic accuracy of the CBCL-MS on data from the TRacking Adolescents'
      Individual Lives Survey (TRAILS), a prospective epidemiological cohort study of
      2230 Dutch youths assessed with the CBCL at ages 11, 13 and 16. At age 19
      lifetime psychiatric diagnoses were ascertained with the Composite International
      Diagnostic Interview. We compared the predictive ability of the CBCL-MS against
      the CBCL-Externalising Scale and the CBCL-PBD in the TRAILS sample. RESULTS: The
      CBCL-MS had high internal consistency and satisfactory accuracy (area under the
      curve = 0.64) in this general population sample. Principal Component Analyses,
      followed by parallel analyses and confirmatory factor analyses, identified four
      factors corresponding to distractibility/disinhibition, psychosis, increased
      libido and disrupted sleep. This factor structure remained stable across all
      assessment ages. Logistic regression analyses showed that the CBCL-MS had
      significantly higher predictive ability than both the other scales. CONCLUSIONS:
      Our data demonstrate that the CBCL-MS is a promising screening instrument for BD.
      The factor structure of the CBCL-MS showed remarkable temporal stability between
      late childhood and early adulthood suggesting that it maps on to meaningful
      developmental dimensions of liability to BD.

PMID- 23967060
TI  - Hidden biodiversity in an ecologically important freshwater amphipod: differences
      in genetic structure between two cryptic species.
AB  - Cryptic species, i.e. species that are morphologically hard to distinguish, have
      been detected repeatedly in various taxa and ecosystems. In order to evaluate the
      importance of this finding, we have to know in how far cryptic species differ in
      various aspects of their biology. The amphipod Gammarus fossarum is a key
      invertebrate in freshwater streams and contains several cryptic species. We
      examined the population genetic structure, genetic diversity and demographic
      history of two of them (type A and type B) using microsatellite markers and asked
      whether they show significant differences. We present results of population
      genetic analyses based on a total of 37 populations from the headwaters of two
      major European drainages, Rhine and Rhone. We found that, in both species,
      genetic diversity was geographically structured among and within drainages. For
      type A in the Rhine and type B in the Rhone, we detected significant patterns of
      isolation by distance. The increase of genetic differentiation with geographical
      distance, however, was much higher in type A than in type B. This result
      indicates substantial interspecific differences in population history and/or the
      extent of current gene flow between populations. In the Rhine, type B does not
      show evidence of isolation by distance, and population differentiation is
      relatively low across hundreds of kilometres. The majority of these populations
      also show signatures of recent bottlenecks. These patterns are consistent with a
      recent expansion of type B into the Rhine drainage. In summary, our results
      suggest considerable and previously unrecognized interspecific differences in the
      genetic structure of these cryptic keystone species. 

PMID- 23967061
TI  - Facebook use predicts declines in subjective well-being in young adults.
AB  - Over 500 million people interact daily with Facebook. Yet, whether Facebook use
      influences subjective well-being over time is unknown. We addressed this issue
      using experience-sampling, the most reliable method for measuring in-vivo
      behavior and psychological experience. We text-messaged people five times per day
      for two-weeks to examine how Facebook use influences the two components of
      subjective well-being: how people feel moment-to-moment and how satisfied they
      are with their lives. Our results indicate that Facebook use predicts negative
      shifts on both of these variables over time. The more people used Facebook at one
      time point, the worse they felt the next time we text-messaged them; the more
      they used Facebook over two-weeks, the more their life satisfaction levels
      declined over time. Interacting with other people "directly" did not predict
      these negative outcomes. They were also not moderated by the size of people's
      Facebook networks, their perceived supportiveness, motivation for using Facebook,
      gender, loneliness, self-esteem, or depression. On the surface, Facebook provides
      an invaluable resource for fulfilling the basic human need for social connection.
      Rather than enhancing well-being, however, these findings suggest that Facebook
      may undermine it. 

PMID- 23967062
TI  - Reconciling forest conservation and logging in Indonesian Borneo.
AB  - Combining protected areas with natural forest timber concessions may sustain
      larger forest landscapes than is possible via protected areas alone. However, the
      role of timber concessions in maintaining natural forest remains poorly
      characterized. An estimated 57% (303,525 km2) of Kalimantan's land area (532,100
      km2) was covered by natural forest in 2000. About 14,212 km2 (4.7%) had been
      cleared by 2010. Forests in oil palm concessions had been reduced by 5,600 km2
      (14.1%), while the figures for timber concessions are 1,336 km2 (1.5%), and for
      protected forests are 1,122 km2 (1.2%). These deforestation rates explain little
      about the relative performance of the different land use categories under
      equivalent conversion risks due to the confounding effects of location. An
      estimated 25% of lands allocated for timber harvesting in 2000 had their status
      changed to industrial plantation concessions in 2010. Based on a sample of 3,391
      forest plots (1*1 km; 100 ha), and matching statistical analyses, 2000-2010
      deforestation was on average 17.6 ha lower (95% C.I.: -22.3 ha- -12.9 ha) in
      timber concession plots than in oil palm concession plots. When location effects
      were accounted for, deforestation rates in timber concessions and protected areas
      were not significantly different (Mean difference: 0.35 ha; 95% C.I.: -0.002 ha
      0.7 ha). Natural forest timber concessions in Kalimantan had similar ability as
      protected areas to maintain forest cover during 2000-2010, provided the former
      were not reclassified to industrial plantation concessions. Our study indicates
      the desirability of the Government of Indonesia designating its natural forest
      timber concessions as protected areas under the IUCN Protected Area Category VI
      to protect them from reclassification.

PMID- 23967063
TI  - The substantial first impact of bottom fishing on rare biodiversity hotspots: a
      dilemma for evidence-based conservation.
AB  - This study describes the impact of the first passage of two types of bottom-towed
      fishing gear on rare protected shellfish-reefs formed by the horse mussel
      Modiolus modiolus (L.). One of the study sites was trawled and the other was
      scallop-dredged. Divers collected HD video imagery of epifauna from quadrats at
      the two study sites and directed infaunal samples from one site. The total number
      of epifaunal organisms was significantly reduced following a single pass of a
      trawl (90%) or scallop dredge (59%), as was the diversity of the associated
      community and the total number of M. modiolus at the trawled site. At both sites
      declines in anthozoans, hydrozoans, bivalves, echinoderms and ascidians accounted
      for most of the change. A year later, no recovery was evident at the trawled site
      and significantly fewer infaunal taxa (polychaetes, malacostracans, bivalves and
      ophuroids) were recorded in the trawl track. The severity of the two types of
      impact reflected the undisturbed status of the habitats compared to previous
      studies. As a 'priority habitat' the nature of the impacts described on M.
      modiolus communities are important to the development of conservation management
      policy and indicators of condition in Marine Protected Areas (EU Habitats
      Directive) as well as indicators of 'Good Environmental Status' under the
      European Union Marine Strategy Framework Directive. Conservation managers are
      under pressure to support decisions with good quality evidence. Elsewhere,
      indirect studies have shown declines of M. modiolus biogenic communities in
      fishing grounds. However, given the protected status of the rare habitat,
      premeditated demonstration of direct impact is unethical or illegal in Marine
      Protected Areas. This study therefore provides a unique opportunity to
      investigate the impact from fishing gear whilst at the same time reflecting on
      the dilemma of evidence-based conservation management. 

PMID- 23967064
TI  - What are the health benefits of active travel? A systematic review of trials and
      cohort studies.
AB  - BACKGROUND: Increasing active travel (primarily walking and cycling) has been
      widely advocated for reducing obesity levels and achieving other population
      health benefits. However, the strength of evidence underpinning this strategy is
      unclear. This study aimed to assess the evidence that active travel has
      significant health benefits. METHODS: The study design was a systematic review of
      (i) non-randomised and randomised controlled trials, and (ii) prospective
      observational studies examining either (a) the effects of interventions to
      promote active travel or (b) the association between active travel and health
      outcomes. Reports of studies were identified by searching 11 electronic
      databases, websites, reference lists and papers identified by experts in the
      field. Prospective observational and intervention studies measuring any health
      outcome of active travel in the general population were included. Studies of
      patient groups were excluded. RESULTS: Twenty-four studies from 12 countries were
      included, of which six were studies conducted with children. Five studies
      evaluated active travel interventions. Nineteen were prospective cohort studies
      which did not evaluate the impact of a specific intervention. No studies were
      identified with obesity as an outcome in adults; one of five prospective cohort
      studies in children found an association between obesity and active travel. Small
      positive effects on other health outcomes were found in five intervention
      studies, but these were all at risk of selection bias. Modest benefits for other
      health outcomes were identified in five prospective studies. There is suggestive
      evidence that active travel may have a positive effect on diabetes prevention,
      which may be an important area for future research. CONCLUSIONS: Active travel
      may have positive effects on health outcomes, but there is little robust evidence
      to date of the effectiveness of active transport interventions for reducing
      obesity. Future evaluations of such interventions should include an assessment of
      their impacts on obesity and other health outcomes.

PMID- 23967065
TI  - Quantifying trends in disease impact to produce a consistent and reproducible
      definition of an emerging infectious disease.
AB  - The proper allocation of public health resources for research and control
      requires quantification of both a disease's current burden and the trend in its
      impact. Infectious diseases that have been labeled as "emerging infectious
      diseases" (EIDs) have received heightened scientific and public attention and
      resources. However, the label 'emerging' is rarely backed by quantitative
      analysis and is often used subjectively. This can lead to over-allocation of
      resources to diseases that are incorrectly labelled "emerging," and insufficient
      allocation of resources to diseases for which evidence of an increasing or high
      sustained impact is strong. We suggest a simple quantitative approach, segmented
      regression, to characterize the trends and emergence of diseases. Segmented
      regression identifies one or more trends in a time series and determines the most
      statistically parsimonious split(s) (or joinpoints) in the time series. These
      joinpoints in the time series indicate time points when a change in trend
      occurred and may identify periods in which drivers of disease impact change. We
      illustrate the method by analyzing temporal patterns in incidence data for twelve
      diseases. This approach provides a way to classify a disease as currently
      emerging, re-emerging, receding, or stable based on temporal trends, as well as
      to pinpoint the time when the change in these trends happened. We argue that
      quantitative approaches to defining emergence based on the trend in impact of a
      disease can, with appropriate context, be used to prioritize resources for
      research and control. Implementing this more rigorous definition of an EID will
      require buy-in and enforcement from scientists, policy makers, peer reviewers and
      journal editors, but has the potential to improve resource allocation for global
      health. 

PMID- 23967066
TI  - L-arginine and vitamin D adjunctive therapies in pulmonary tuberculosis: a
      randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Vitamin D (vitD) and L-arginine have important antimycobacterial
      effects in humans. Adjunctive therapy with these agents has the potential to
      improve outcomes in active tuberculosis (TB). METHODS: In a 4-arm randomised,
      double-blind, placebo-controlled factorial trial in adults with smear-positive
      pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral
      adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g
      daily or matching placebo, for 8 weeks, on proportions of participants with
      negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1,
      cough, sputum, haemoptysis). All participants with available endpoints were
      included in analyses according to the study arm to which they were originally
      assigned. Adults with new smear-positive PTB were eligible. The trial was
      registered at ClinicalTrials.gov NCT00677339. RESULTS: 200 participants were
      enrolled, less than the intended sample size: 50 received L-arginine + active
      vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine +
      active vitD and 50 received placebo L-arginine + placebo vitD. According to the
      factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin
      D, 99 placebo vitamin D. Results for the primary endpoints were available in 155
      (4-week culture) and 167 (clinical score) participants. Sputum culture conversion
      was achieved by week 4 in 48/76 (63%) participants in the active L-arginine
      versus 48/79 (61%) in placebo L-arginine arms (risk difference -3%, 95% CI -19 to
      13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo
      vitD arms (risk difference 7%, 95% CI -9 to 22%). The mean clinical outcome score
      also did not differ between study arms. There were no effects of the
      interventions on adverse event rates including hypercalcaemia, or other secondary
      outcomes. CONCLUSION: Neither vitD nor L-arginine supplementation, at the doses
      administered and with the power attained, affected TB outcomes. REGISTRY:
      ClinicalTrials.gov. Registry number: NCT00677339.

PMID- 23967067
TI  - ABC transporters in Dictyostelium discoideum development.
AB  - ATP-binding cassette (ABC) transporters can translocate a broad spectrum of
      molecules across the cell membrane including physiological cargo and toxins. ABC
      transporters are known for the role they play in resistance towards anticancer
      agents in chemotherapy of cancer patients. There are 68 ABC transporters
      annotated in the genome of the social amoeba Dictyostelium discoideum. We have
      characterized more than half of these ABC transporters through a systematic study
      of mutations in their genes. We have analyzed morphological and transcriptional
      phenotypes for these mutants during growth and development and found that most of
      the mutants exhibited rather subtle phenotypes. A few of the genes may share
      physiological functions, as reflected in their transcriptional phenotypes. Since
      most of the abc-transporter mutants showed subtle morphological phenotypes, we
      utilized these transcriptional phenotypes to identify genes that are important
      for development by looking for transcripts whose abundance was unperturbed in
      most of the mutants. We found a set of 668 genes that includes many validated D.
      discoideum developmental genes. We have also found that abcG6 and abcG18 may have
      potential roles in intercellular signaling during terminal differentiation of
      spores and stalks. 

PMID- 23967068
TI  - Neighborhood ethnic diversity and behavioral and emotional problems in 3 year
      olds: results from the Generation R Study.
AB  - BACKGROUND: Studies suggest that neighborhood ethnic diversity may be important
      when it comes to understanding ethnic inequalities in mental health. The primary
      aim of this study was to investigate whether neighborhood ethnic diversity
      moderated the association between the ethnic minority status and child behavioral
      and emotional problems. METHODS: We included 3076 preschoolers participating in
      the Generation R Study, a birth cohort study in Rotterdam, the Netherlands. At
      child age 3-years, parents completed the Child Behavior Checklist (CBCL/1,5-5).
      Individual-level data, assessed with questionnaires, was combined with
      neighborhood-level data. Multi-level logistic regression models predicted the
      Odds Ratios for the CBCL total problems score as a function of maternal ethnic
      background and neighborhood ethnic diversity, computed with the Racial Diversity
      Index and categorized into tertiles. Interaction on the additive scale was
      assessed using Relative Access Risk due to Interaction. RESULTS: Being from an
      ethnic minority was associated with child behavioral and emotional problems in
      unadjusted (OR 2.76, 95% CI 1.88-4.04) and adjusted models (OR 2.64, 95% CI 1.79
      3.92). Residing in a high diversity neighborhood was associated with child
      behavioral and emotional problems in unadjusted (OR 2.03, 95% CI 1.13-3.64) but
      not in adjusted models (OR 0.89, 95% CI 0.51-1.57). When stratifying by the three
      levels of neighborhood ethnic diversity, ethnic inequalities in behavioral and
      emotional problems were greatest in low diversity neighborhoods (OR 5.24, 95%CI
      2.47-11.14), smaller in high diversity neighborhoods (OR 3.15, 95% CI 1.66-5.99)
      and smallest in medium diversity neighborhoods (OR 1.59, 95% CI 0.90-2.82). Tests
      for interaction (when comparing medium to low diversity neighborhoods) trended
      towards negative on both the additive and multiplicative scale for the maternal
      report (RERI: -3.22, 95% CI -0.70-0.59; Ratio of ORs: 0.30, 95% CI 0.12-0.76).
      CONCLUSION: This study suggests that ethnic inequalities in child behavioral and
      emotional problems may be greatest in ethnically homogeneous neighborhoods.

PMID- 23967069
TI  - Adolescent abstinence and unprotected sex in CyberSenga, an Internet-based HIV
      prevention program: randomized clinical trial of efficacy.
AB  - CONTEXT: Cost-effective, scalable programs are urgently needed in countries
      deeply affected by HIV. METHODS: This parallel-group RCT was conducted in four
      secondary schools in Mbarara, Uganda. Participants were 12 years and older,
      reported past-year computer or Internet use, and provided informed caregiver
      permission and youth assent. The intervention, CyberSenga, was a five-hour online
      healthy sexuality program. Half of the intervention group was further randomized
      to receive a booster at four-months post-intervention. The control arm received
      'treatment as usual' (i.e., school-delivered sexuality programming). The main
      outcome measures were: 1) condom use and 2) abstinence in the past three months
      at six-months' post-intervention. Secondary outcomes were: 1) condom use and 2)
      abstinence at three-month's post-intervention; and 6-month outcomes by booster
      exposure. Analyses were intention to treat. RESULTS: All 416 eligible youth were
      invited to participate, 88% (n = 366) of whom enrolled. Participants were
      randomized to the intervention (n = 183) or control (n = 183) arm; 91
      intervention participants were further randomized to the booster. No
      statistically significant results were noted among the main outcomes. Among the
      secondary outcomes: At three-month follow-up, trends suggested that intervention
      participants (81%) were more likely to be abstinent than control participants
      (74%; p = 0.08), and this was particularly true among youth who were abstinent at
      baseline (88% vs. 77%; p = 0.02). At six-month follow-up, those in the booster
      group (80%) reported higher rates of abstinence than youth in the intervention,
      no booster (57%) and control (55%) groups (p = 0.15); they also reported lower
      rates of unprotected sex (5%) compared to youth in the intervention, no booster
      (24%) and control (21%) groups (p = 0.21) among youth sexually active at
      baseline. CONCLUSIONS: The CyberSenga program may affect HIV preventive behavior
      among abstinent youth in the short term and, with the booster, may also promote
      HIV preventive behavior among sexually active youth in the longer term. TRIAL
      REGISTRATION: NCT00906178.

PMID- 23967070
TI  - Visualisation of gammaH2AX foci caused by heavy ion particle traversal;
      distinction between core track versus non-track damage.
AB  - Heavy particle irradiation produces complex DNA double strand breaks (DSBs) which
      can arise from primary ionisation events within the particle trajectory.
      Additionally, secondary electrons, termed delta-electrons, which have a range of
      distributions can create low linear energy transfer (LET) damage within but also
      distant from the track. DNA damage by delta-electrons distant from the track has
      not previously been carefully characterised. Using imaging with deconvolution, we
      show that at 8 hours after exposure to Fe (~200 keV/um) ions, gammaH2AX foci
      forming at DSBs within the particle track are large and encompass multiple
      smaller and closely localised foci, which we designate as clustered gammaH2AX
      foci. These foci are repaired with slow kinetics by DNA non-homologous end
      joining (NHEJ) in G1 phase with the magnitude of complexity diminishing with
      time. These clustered foci (containing 10 or more individual foci) represent a
      signature of DSBs caused by high LET heavy particle radiation. We also identified
      simple gammaH2AX foci distant from the track, which resemble those arising after
      X-ray exposure, which we attribute to low LET delta-electron induced DSBs. They
      are rapidly repaired by NHEJ. Clustered gammaH2AX foci induced by heavy particle
      radiation cause prolonged checkpoint arrest compared to simple gammaH2AX foci
      following X-irradiation. However, mitotic entry was observed when ~10 clustered
      foci remain. Thus, cells can progress into mitosis with multiple clusters of DSBs
      following the traversal of a heavy particle. 

PMID- 23967071
TI  - An indirubin derivative, indirubin-3'-monoxime suppresses oral cancer
      tumorigenesis through the downregulation of survivin.
AB  - Oral cancer is the fourth most common cause of death from cancer in Taiwanese
      men. Indirubin-3'-monoxime (I3M), a potent cyclin-dependent kinase inhibitor, has
      therapeutic effects in other cancer cells. In this study, we carried out in vitro
      assays to test cell viability, cell cycle progression, apoptosis, cell migration
      and invasion in this cancer type. In addition, using an oral tumorigenic animal
      model, we examined target gene and protein expression using real time qPCR,
      immunoblotting and immunohistochemical staining. Our results demonstrate that I3M
      has an anti-proliferative effect in both Cal-27 and HSC-3 oral cancer cell lines
      and that treatment of Cal-27 and HSC-3 cells with I3M results in apoptosis
      through the activation of cytochrome c. In addition, I3M interrupts the cell
      cycle in Cal-27 cells in a dose-dependent manner by arresting cells in the G2/M
      phase. We also found that I3M suppresses migration and invasion in Cal-27 cells
      by inhibiting the expression of focal adhesion kinase, urokinase-type plasminogen
      inhibitor, and matrix metalloproteinase 9. Moreover, we identified survivin as a
      target protein in I3M-treated oral cancer cells. Using an oral cancer mouse
      model, we demonstrate that topical application of an adhesive gel composed of I3M
      and poly(vinyl alcohol) (I3M/PVA) has dose-dependent anti-tumorigenic effects.
      Following treatment, the expression of survivin protein and mRNA was
      downregulated in cancerous tissues. Furthermore, plasma survivin levels were also
      reduced in the I3M-treated mice. These results suggest that topical application
      of I3M, a drug synthesized from indirubin, which is found in Qing-Dai - has
      therapeutic potential for treating oral cancer. 

PMID- 23967073
TI  - Explaining marital patterns and trends in namibia: a regression analysis of 1992,
      2000 and 2006 demographic and survey data.
AB  - BACKGROUND: Marriage is a significant event in life-course of individuals, and
      creates a system that characterizes societal and economic structures. Marital
      patterns and dynamics over the years have changed a lot, with decreasing
      proportions of marriage, increased levels of divorce and co-habitation in
      developing countries. Although, such changes have been reported in African
      societies including Namibia, they have largely remained unexplained. OBJECTIVES
      AND METHODS: IN THIS PAPER, WE EXAMINED TRENDS AND PATTERNS OF MARITAL STATUS OF
      WOMEN OF MARRIAGEABLE AGE: 15 to 49 years, in Namibia using the 1992, 2000 and
      2006 Demographic and Health Survey (DHS) data. Trends were established for
      selected demographic variables. Two binary logistic regression models for ever
      married versus never married, and cohabitation versus married were fitted to
      establish factors associated with such nuptial systems. Further a multinomial
      logistic regression models, adjusted for bio-demographic and socio-economic
      variables, were fitted separately for each year, to establish determinants of
      type of union (never married, married and cohabitation). RESULTS AND CONCLUSIONS:
      Findings indicate a general change away from marriage, with a shift in singulate
      mean age at marriage. Cohabitation was prevalent among those less than 30 years
      of age, the odds were higher in urban areas and increased since 1992. Be as it
      may marriage remained a persistent nuptiality pattern, and common among the less
      educated and employed, but lower odds in urban areas. Results from multinomial
      model suggest that marital status was associated with age at marriage, total
      children born, region, place of residence, education level and religion. We
      conclude that marital patterns have undergone significant transformation over the
      past two decades in Namibia, with a coexistence of traditional marriage framework
      with co-habitation, and sizeable proportion remaining unmarried to the late 30s.
      A shift in the singulate mean age is becoming distinctive in the Namibian
      society.

PMID- 23967072
TI  - Identification of multiple subsets of ventral interneurons and differential
      distribution along the rostrocaudal axis of the developing spinal cord.
AB  - The spinal cord contains neuronal circuits termed Central Pattern Generators
      (CPGs) that coordinate rhythmic motor activities. CPG circuits consist of motor
      neurons and multiple interneuron cell types, many of which are derived from four
      distinct cardinal classes of ventral interneurons, called V0, V1, V2 and V3.
      While significant progress has been made on elucidating the molecular and genetic
      mechanisms that control ventral interneuron differentiation, little is known
      about their distribution along the antero-posterior axis of the spinal cord and
      their diversification. Here, we report that V0, V1 and V2 interneurons exhibit
      distinct organizational patterns at brachial, thoracic and lumbar levels of the
      developing spinal cord. In addition, we demonstrate that each cardinal class of
      ventral interneurons can be subdivided into several subsets according to the
      combinatorial expression of different sets of transcription factors, and that
      these subsets are differentially distributed along the rostrocaudal axis of the
      spinal cord. This comprehensive molecular profiling of ventral interneurons
      provides an important resource for investigating neuronal diversification in the
      developing spinal cord and for understanding the contribution of specific
      interneuron subsets on CPG circuits and motor control. 

PMID- 23967074
TI  - Hospital admissions in children with down syndrome: experience of a population
      based cohort followed from birth.
AB  - OBJECTIVE: Children with Down syndrome, the most common genetic cause of
      intellectual disability, are prone to multiple and varied health-related
      problems. This study describes patterns of hospitalisations for children and
      young people with Down syndrome in Western Australia. METHODS: Birth records were
      linked to the Western Australian population-based Intellectual Disability
      database to identify all children born with Down syndrome in Western Australia
      between 1 January, 1983 and 31 December, 1999. These records were linked to the
      Hospital Morbidity Data System to provide information on all hospitalisations up
      to 31 December, 2004. Hospitalisation data, coded using ICD-9CM or ICD-10 (v0.5)
      were grouped into clinically relevant categories using the primary diagnosis.
      Rates of hospital admission for all and specific diagnoses were expressed in 1000
      person-years at-risk and median age at first admission and length of stay were
      calculated. RESULTS: Of the 405 children, 395 had one or more hospital
      admissions, totalling 3786 admissions for all children and an estimated 39.5
      person-years in hospital. On average, children were admitted 9.7 times, with an
      estimated rate of 757.2 admissions per 1000pyr (95% CI: 680, 843). A quarter of
      all admissions occurred in the first year of life. The average hospital length of
      stay was 3.8 days (95% CI: 3.7, 4.1). Upper respiratory tract conditions affected
      the most children (58.5%) and accounted for 12.1% of all admissions. Other
      disorders which affected a high percentage of children were ear/hearing
      conditions (50.6%), disorders of the oral cavity (38.0%) and lower respiratory
      tract conditions (37.5%). Overall, children with Down syndrome were hospitalised
      at a rate five times (95% CI = 4.3-6.2) that of the general population.
      CONCLUSION: Children with Down syndrome are at increased risk of morbidity for
      varied causes underlining the importance of comprehensive and targeted primary
      care for this group.

PMID- 23967075
TI  - A mathematical model of the metabolic and perfusion effects on cortical spreading
      depression.
AB  - Cortical spreading depression (CSD) is a slow-moving ionic and metabolic
      disturbance that propagates in cortical brain tissue. In addition to massive
      cellular depolarizations, CSD also involves significant changes in perfusion and
      metabolism-aspects of CSD that had not been modeled and are important to
      traumatic brain injury, subarachnoid hemorrhage, stroke, and migraine. In this
      study, we develop a mathematical model for CSD where we focus on modeling the
      features essential to understanding the implications of neurovascular coupling
      during CSD. In our model, the sodium-potassium-ATPase, mainly responsible for
      ionic homeostasis and active during CSD, operates at a rate that is dependent on
      the supply of oxygen. The supply of oxygen is determined by modeling blood flow
      through a lumped vascular tree with an effective local vessel radius that is
      controlled by the extracellular potassium concentration. We show that during CSD,
      the metabolic demands of the cortex exceed the physiological limits placed on
      oxygen delivery, regardless of vascular constriction or dilation. However,
      vasoconstriction and vasodilation play important roles in the propagation of CSD
      and its recovery. Our model replicates the qualitative and quantitative behavior
      of CSD--vasoconstriction, oxygen depletion, extracellular potassium elevation,
      prolonged depolarization--found in experimental studies. We predict faster,
      longer duration CSD in vivo than in vitro due to the contribution of the
      vasculature. Our results also help explain some of the variability of CSD between
      species and even within the same animal. These results have clinical and
      translational implications, as they allow for more precise in vitro, in vivo, and
      in silico exploration of a phenomenon broadly relevant to neurological disease.

PMID- 23967076
TI  - The influence of relatives on the efficiency and error rate of familial
      searching.
AB  - We investigate the consequences of adopting the criteria used by the state of
      California, as described by Myers et al. (2011), for conducting familial
      searches. We carried out a simulation study of randomly generated profiles of
      related and unrelated individuals with 13-locus CODIS genotypes and YFiler(r) Y
      chromosome haplotypes, on which the Myers protocol for relative identification
      was carried out. For Y-chromosome sharing first degree relatives, the Myers
      protocol has a high probability (80~99%) of identifying their relationship. For
      unrelated individuals, there is a low probability that an unrelated person in the
      database will be identified as a first-degree relative. For more distant Y
      haplotype sharing relatives (half-siblings, first cousins, half-first cousins or
      second cousins) there is a substantial probability that the more distant relative
      will be incorrectly identified as a first-degree relative. For example, there is
      a 3~18% probability that a first cousin will be identified as a full sibling,
      with the probability depending on the population background. Although the
      California familial search policy is likely to identify a first degree relative
      if his profile is in the database, and it poses little risk of falsely
      identifying an unrelated individual in a database as a first-degree relative,
      there is a substantial risk of falsely identifying a more distant Y-haplotype
      sharing relative in the database as a first-degree relative, with the consequence
      that their immediate family may become the target for further investigation. This
      risk falls disproportionately on those ethnic groups that are currently
      overrepresented in state and federal databases.

PMID- 23967077
TI  - Direct diabetes-related costs in young patients with early-onset, long-lasting
      type 1 diabetes.
AB  - OBJECTIVE: To estimate diabetes-related direct health care costs in pediatric
      patients with early-onset type 1 diabetes of long duration in Germany. RESEARCH
      DESIGN AND METHODS: Data of a population-based cohort of 1,473 subjects with type
      1 diabetes onset at 0-4 years of age within the years 1993-1999 were included
      (mean age 13.9 (SD 2.2) years, mean diabetes duration 10.9 (SD 1.9) years, as of
      31.12.2007). Diabetes-related health care services utilized in 2007 were derived
      from a nationwide prospective documentation system (DPV). Health care utilization
      was valued in monetary terms based on inpatient and outpatient medical fees and
      retail prices (perspective of statutory health insurance). Multiple regression
      models were applied to assess associations between direct diabetes-related health
      care costs per patient-year and demographic and clinical predictors. RESULTS:
      Mean direct diabetes-related health care costs per patient-year were ?3,745
      (inter-quartile range: 1,943-4,881). Costs for glucose self-monitoring were the
      main cost category (28.5%), followed by costs for continuous subcutaneous insulin
      infusion (25.0%), diabetes-related hospitalizations (22.1%) and insulin (18.4%).
      Female gender, pubertal age and poor glycemic control were associated with higher
      and migration background with lower total costs. CONCLUSIONS: Main cost
      categories in patients with on average 11 years of diabetes duration were costs
      for glucose self-monitoring, insulin pump therapy, hospitalization and insulin.
      Optimization of glycemic control in particular in pubertal age through
      intensified care with improved diabetes education and tailored insulin regimen,
      can contribute to the reduction of direct diabetes-related costs in this patient
      group.

PMID- 23967078
TI  - Oncosuppressive suicide gene virotherapy "PVH1-yCD/5-FC" for pancreatic
      peritoneal carcinomatosis treatment: NFkappaB and Akt/PI3K involvement.
AB  - Peritoneal carcinomatosis is common in advanced pancreatic cancer. Despite
      current standard treatment, patients with this disease until recently were
      considered incurable. Cancer gene therapy using oncolytic viruses have generated
      much interest over the past few years. Here, we investigated a new gene directed
      enzyme prodrug therapy (GDEPT) approach for an oncosuppressive virotherapy
      strategy using parvovirus H1 (PV-H1) which preferentially replicates and kills
      malignant cells. Although, PV-H1 is not potent enough to destroy tumors, it
      represents an attractive vector for cancer gene therapy. We therefore sought to
      determine whether the suicide gene/prodrug system, yCD/5-FC could be rationally
      combined to PV-H1 augmenting its intrinsic oncolytic activity for pancreatic
      cancer prevention and treatment. We showed that the engineered recombinant
      parvovirus rPVH1-yCD with 5-FC treatment increased significantly the intrinsic
      cytotoxic effect and resulted in potent induction of apoptosis and tumor growth
      inhibition in chemosensitive and chemoresistant cells. Additionally, the suicide
      gene-expressing PV-H1 infection reduced significantly the constitutive activities
      of NFkappaB and Akt/PI3K. Combination of their pharmacological inhibitors (MG132
      and LY294002) with rPVH1-yCD/5-FC resulted in substantial increase of antitumor
      activity. In vivo, high and sustained expression of NS1 and yCD was observed in
      the disseminated tumor nodules and absent in normal tissues. Treatment of mice
      bearing intraperitoneal pancreatic carcinomatosis with rPVH1-yCD/5-FC resulted in
      a drastic inhibition of tumor cell spreading and subsequent increase in long-term
      survival. Together, the presented data show the improved oncolytic activity of
      wPV-H1 by yCD/5-FC and thus provides valuable effective and promising virotherapy
      strategy for prevention of tumor recurrence and treatment. In the light of this
      study, the suicide gene parvovirotherapy approach represents a new weapon in the
      war against pancreatic cancer. Moreover, these preliminary accomplishments are
      opening new field for future development of new combined targeted therapies to
      have a meaningful impact on advanced cancer. 

PMID- 23967079
TI  - A panel of 4 microRNAs facilitates the prediction of left ventricular
      contractility after acute myocardial infarction.
AB  - BACKGROUND: Prediction of clinical outcome after acute myocardial infarction
      (AMI) is challenging and would benefit from new biomarkers. We investigated the
      prognostic value of 4 circulating microRNAs (miRNAs) after AMI. METHODS: We
      enrolled 150 patients after AMI. Blood samples were obtained at discharge for
      determination of N-terminal pro-brain natriuretic peptide (Nt-proBNP) and levels
      of miR-16, miR-27a, miR-101 and miR-150. Patients were assessed by
      echocardiography at 6 months follow-up and the wall motion index score (WMIS) was
      used as an indicator of left ventricular (LV) contractility. We assessed the
      added predictive value of miRNAs against a multi-parameter clinical model
      including Nt-proBNP. RESULTS: Patients with anterior AMI and elevated Nt-proBNP
      levels at discharge from the hospital were at high risk of subsequent impaired LV
      contractility (follow-up WMIS>1.2, n = 71). A combination of the 4 miRNAs (miR
      16/27a/101/150) improved the prediction of LV contractility based on clinical
      variables (P = 0.005). Patients with low levels of miR-150 (odds ratio [95%
      confidence interval] 0.08 [0.01-0.48]) or miR-101 (0.19 [0.04-0.97]) and elevated
      levels of miR-16 (15.9 [2.63-95.91]) or miR-27a (4.18 [1.36-12.83]) were at high
      risk of impaired LV contractility. The 4 miRNA panel reclassified a significant
      proportion of patients with a net reclassification improvement of 66% (P =
      0.00005) and an integrated discrimination improvement of 0.08 (P = 0.001).
      CONCLUSION: Our results indicate that panels of miRNAs may aid in prognostication
      of outcome after AMI.

PMID- 23967080
TI  - Perinatal supplementation with omega-3 polyunsaturated fatty acids improves
      sevoflurane-induced neurodegeneration and memory impairment in neonatal rats.
AB  - OBJECTIVES: To investigate if perinatal Omega-3 polyunsaturated fatty acids (n-3
      PUFAs) supplementation can improve sevoflurane-induced neurotoxicity and
      cognitive impairment in neonatal rats. METHODS: Female Sprague-Dawley rats (n = 3
      each group) were treated with or without an n-3 PUFAs (fish oil) enriched diet
      from the second day of pregnancy to 14 days after parturition. The offspring rats
      (P7) were treated with six hours sevoflurane administration (one group without
      sevoflurane/prenatal n-3 PUFAs supplement as control). The 5-bromodeoxyuridine
      (Brdu) was injected intraperitoneally during and after sevoflurane anesthesia to
      assess dentate gyrus (DG) progenitor proliferation. Brain tissues were harvested
      and subjected to Western blot and immunohistochemistry respectively. Morris water
      maze spatial reference memory, fear conditioning, and Morris water maze memory
      consolidation were tested at P35, P63 and P70 (n = 9), respectively. RESULTS: Six
      hours 3% sevoflurane administration increased the cleaved caspase-3 in the
      thalamus, parietal cortex but not hippocampus of neonatal rat brain. Sevoflurane
      anesthesia also decreased the neuronal precursor proliferation of DG in rat
      hippocampus. However, perinatal n-3 PUFAs supplement could decrease the cleaved
      caspase-3 in the cerebral cortex of neonatal rats, and mitigate the decrease in
      neuronal proliferation in their hippocampus. In neurobehavioral studies, compared
      with control and n-3 PUFAs supplement groups, we did not find significant spatial
      cognitive deficit and early long-term memory impairment in sevoflurane
      anesthetized neonatal rats at their adulthood. However, sevoflurane could impair
      the immediate fear response and working memory and short-term memory. And n-3
      PUFAs could improve neurocognitive function in later life after neonatal
      sevoflurane exposure. CONCLUSION: Our study demonstrated that neonatal exposure
      to prolonged sevoflurane could impair the immediate fear response, working memory
      and short-term memory of rats at their adulthood, which may through inducing
      neuronal apoptosis and decreasing neurogenesis. However, these sevoflurane
      induced unfavorable neuronal effects can be mitigated by perinatal n-3 PUFAs
      supplementation.

PMID- 23967081
TI  - Assessment of fusion gene status in sarcomas using a custom made fusion gene
      microarray.
AB  - Sarcomas are relatively rare malignancies and include a large number of
      histological subgroups. Based on morphology alone, the differential diagnoses of
      sarcoma subtypes can be challenging, but the identification of specific fusion
      genes aids correct diagnostication. The presence of individual fusion products
      are routinely investigated in Pathology labs. However, the methods used are time
      consuming and based on prior knowledge about the expected fusion gene and often
      the most likely break-point. In this study, 16 sarcoma samples, representing
      seven different sarcoma subtypes with known fusion gene status from a diagnostic
      setting, were investigated using a fusion gene microarray. The microarray was
      designed to detect all possible exon-exon breakpoints between all known fusion
      genes in a single analysis. An automated scoring of the microarray data from the
      38 known sarcoma-related fusion genes identified the correct fusion gene among
      the top-three hits in 11 of the samples. The analytical sensitivity may be
      further optimised, but we conclude that a sarcoma-fusion gene microarray is
      suitable as a time-saving screening tool to identify the majority of the correct
      fusion genes. 

PMID- 23967082
TI  - Discovery of J chain in African lungfish (Protopterus dolloi, Sarcopterygii)
      using high throughput transcriptome sequencing: implications in mucosal immunity.
AB  - J chain is a small polypeptide responsible for immunoglobulin (Ig) polymerization
      and transport of Igs across mucosal surfaces in higher vertebrates. We identified
      a J chain in dipnoid fish, the African lungfish (Protopterus dolloi) by high
      throughput sequencing of the transcriptome. P. dolloi J chain is 161 aa long and
      contains six of the eight Cys residues present in mammalian J chain. Phylogenetic
      studies place the lungfish J chain closer to tetrapod J chain than to the
      coelacanth or nurse shark sequences. J chain expression occurs in all P. dolloi
      immune tissues examined and it increases in the gut and kidney in response to an
      experimental bacterial infection. Double fluorescent in-situ hybridization shows
      that 88.5% of IgM+ cells in the gut co-express J chain, a significantly higher
      percentage than in the pre-pyloric spleen. Importantly, J chain expression is not
      restricted to the B-cell compartment since gut epithelial cells also express J
      chain. These results improve our current view of J chain from a phylogenetic
      perspective.

PMID- 23967083
TI  - Can topical insect repellents reduce malaria? A cluster-randomised controlled
      trial of the insect repellent N,N-diethyl-m-toluamide (DEET) in Lao PDR.
AB  - BACKGROUND: Mosquito vectors of malaria in Southeast Asia readily feed outdoors
      making malaria control through indoor insecticides such as long-lasting
      insecticidal nets (LLINs) and indoor residual spraying more difficult. Topical
      insect repellents may be able to protect users from outdoor biting, thereby
      providing additional protection above the current best practice of LLINs. METHODS
      AND FINDINGS: A double blind, household randomised, placebo-controlled trial of
      insect repellent to reduce malaria was carried out in southern Lao PDR to
      determine whether the use of repellent and long-lasting insecticidal nets (LLINs)
      could reduce malaria more than LLINs alone. A total of 1,597 households,
      including 7,979 participants, were recruited in June 2009 and April 2010. Equal
      group allocation, stratified by village, was used to randomise 795 households to
      a 15% DEET lotion and the remainder were given a placebo lotion. Participants,
      field staff and data analysts were blinded to the group assignment until data
      analysis had been completed. All households received new LLINs. Participants were
      asked to apply their lotion to exposed skin every evening and sleep under the
      LLINs each night. Plasmodium falciparum and P. vivax cases were actively
      identified by monthly rapid diagnostic tests. Intention to treat analysis found
      no effect from the use of repellent on malaria incidence (hazard ratio: 1.00, 95%
      CI: 0.99-1.01, p = 0.868). A higher socio-economic score was found to
      significantly decrease malaria risk (hazard ratio: 0.72, 95% CI: 0.58-0.90, p =
      0.004). Women were also found to have a reduced risk of infection (hazard ratio:
      0.59, 95% CI: 0.37-0.92, p = 0.020). According to protocol analysis which
      excluded participants using the lotions less than 90% of the time found similar
      results with no effect from the use of repellent. CONCLUSIONS: This randomised
      controlled trial suggests that topical repellents are not a suitable intervention
      in addition to LLINs against malaria amongst agricultural populations in southern
      Lao PDR. These results are also likely to be applicable to much of the Greater
      Mekong Sub-region. TRIAL REGISTRATION: This trial is registered with number
      NCT00938379.

PMID- 23967084
TI  - Localisation of nursery areas based on comparative analyses of the horizontal and
      vertical distribution patterns of juvenile Baltic cod (Gadus morhua).
AB  - Knowledge of the spatial distribution of juvenile cod is essential for obtaining
      precise recruitment data to conduct sustainable management of the eastern and
      western Baltic cod stocks. In this study, the horizontal and vertical
      distribution and density patterns of settled juvenile 0- and 1-group Baltic cod
      are determined, and their nursery areas are localised according to the
      environmental factors affecting them. Comparative statistical analyses of
      biological, hydrographic and hydroacoustic data are carried out based on standard
      ICES demersal trawl surveys and special integrated trawl and acoustic research
      surveys. Horizontal distribution maps for the 2001-2010 cohorts of juvenile cod
      are further generated by applying a statistical log-Gaussian Cox process model to
      the standard trawl survey data. The analyses indicate size-dependent horizontal
      and distinct vertical and diurnal distribution patterns related to the seabed
      topography, water layer depth, and the presence of hydrographic frontal zones
      (pycnoclines) as well as intraspecific patterns in relation to the presence of
      adult cod. The extent of the nursery areas also depends on the cod year class
      strength. Juvenile cod (>=3 cm) are present in all areas of the central Baltic
      Sea (CBS), showing broad dispersal. However, their highest density in the Baltic
      Basins is found at localities with a 40-70 m bottom depth in waters with oxygen
      concentrations above 2 ml O2.l-1 and temperatures above 5 degrees C. The smallest
      juveniles are also found in deep sea localities down to a 100 m depth and at
      oxygen concentrations between 2-4 ml O2.l-1. The vertical, diurnally stratified
      and repeated trawling and hydroacoustic target strength-depth distributions
      obtained from the special surveys show juvenile cod concentrations in frontal
      zone water layers (pycnocline). However, the analyses indicate that in the CBS,
      juvenile cod of all sizes do not appear to aggregate in dense schooling patterns,
      which differs from what has been reported from the North Sea.

PMID- 23967085
TI  - Aureolib - a proteome signature library: towards an understanding of
      staphylococcus aureus pathophysiology.
AB  - Gel-based proteomics is a powerful approach to study the physiology of
      Staphylococcus aureus under various growth restricting conditions. We analyzed
      679 protein spots from a reference 2-dimensional gel of cytosolic proteins of S.
      aureus COL by mass spectrometry resulting in 521 different proteins. 4,692 time
      dependent protein synthesis profiles were generated by exposing S. aureus to nine
      infection-related stress and starvation stimuli (H2O2, diamide, paraquat, NO,
      fermentation, nitrate respiration, heat shock, puromycin, mupirocin). These
      expression profiles are stored in an online resource called Aureolib
      (http://www.aureolib.de). Moreover, information on target genes of 75 regulators
      and regulatory elements were included in the database. Cross-comparisons of this
      extensive data collection of protein synthesis profiles using the tools
      implemented in Aureolib lead to the identification of stress and starvation
      specific marker proteins. Altogether, 226 protein synthesis profiles showed
      induction ratios of 2.5-fold or higher under at least one of the tested
      conditions with 157 protein synthesis profiles specifically induced in response
      to a single stimulus. The respective proteins might serve as marker proteins for
      the corresponding stimulus. By contrast, proteins whose synthesis was increased
      or repressed in response to more than four stimuli are rather exceptional. The
      only protein that was induced by six stimuli is the universal stress protein
      SACOL1759. Most strikingly, cluster analyses of synthesis profiles of proteins
      differentially synthesized under at least one condition revealed only in rare
      cases a grouping that correlated with known regulon structures. The most
      prominent examples are the GapR, Rex, and CtsR regulon. In contrast, protein
      synthesis profiles of proteins belonging to the CodY and sigma(B) regulon are
      widely distributed. In summary, Aureolib is by far the most comprehensive protein
      expression database for S. aureus and provides an essential tool to decipher more
      complex adaptation processes in S. aureus during host pathogen interaction. 

PMID- 23967086
TI  - Role of PPARalpha and HNF4alpha in stress-mediated alterations in lipid
      homeostasis.
AB  - Stress is a risk factor for several cardiovascular pathologies. PPARalpha holds a
      fundamental role in control of lipid homeostasis by directly regulating genes
      involved in fatty acid transport and oxidation. Importantly, PPARalpha agonists
      are effective in raising HDL-cholesterol and lowering triglycerides, properties
      that reduce the risk for cardiovascular diseases. This study investigated the
      role of stress and adrenergic receptor (AR)-related pathways in PPARalpha and
      HNF4alpha regulation and signaling in mice following repeated restraint stress or
      treatment with AR-antagonists administered prior to stress to block AR-linked
      pathways. Repeated restraint stress up-regulated Pparalpha and its target genes
      in the liver, including Acox, Acot1, Acot4, Cyp4a10, Cyp4a14 and Lipin2, an
      effect that was highly correlated with Hnf4alpha. In vitro studies using primary
      hepatocyte cultures treated with epinephrine or AR-agonists confirmed that
      hepatic AR/cAMP/PKA/CREB- and JNK-linked pathways are involved in PPARalpha and
      HNF4alpha regulation. Notably, restraint stress, independent of PPARalpha,
      suppressed plasma triglyceride levels. This stress-induced effect could be
      attributed in part to hormone sensitive lipase activation in the white adipose
      tissue, which was not prevented by the increased levels of perilipin. Overall,
      this study identifies a mechanistic basis for the modification of lipid
      homeostasis following stress and potentially indicates novel roles for PPARalpha
      and HNF4alpha in stress-induced lipid metabolism. 

PMID- 23967087
TI  - A ZO-1/alpha5beta1-integrin complex regulates cytokinesis downstream of
      PKCepsilon in NCI-H460 cells plated on fibronectin.
AB  - Recently, we demonstrated that integrin adhesion to the extracellular matrix at
      the cleavage furrow is essential for cytokinesis of adherent cells. Here, we
      report that tight junction protein ZO-1 (Zonula Occludens-1) is required for
      successful cytokinesis in NCI-H460 cells plated on fibronectin. This function of
      ZO-1 involves interaction with the cytoplasmic domain of alpha5-integrin to
      facilitate recruitment of active fibronectin-binding integrins to the base of the
      cleavage furrow. In the absence of ZO-1, or a functional ZO-1/alpha5beta1
      integrin complex, proper actin-dependent constriction between daughter cells is
      impaired and cells fail cytokinesis. Super-resolution microscopy reveals that in
      ZO-1 depleted cells the furrow becomes delocalized from the matrix. We also show
      that PKCepsilon-dependent phosphorylation at Serine168 is required for ZO-1
      localization to the furrow and successful cell division. Altogether, our results
      identify a novel regulatory pathway involving the interplay between ZO-1, alpha5
      integrin and PKCepsilon in the late stages of mammalian cell division. 

PMID- 23967088
TI  - An in silico analysis of troponin I mutations in hypertrophic cardiomyopathy of
      Indian origin.
AB  - Hypertrophic Cardiomyopathy (HCM) is an autosomal dominant disorder of the
      myocardium which is hypertrophied resulting in arrhythmias and heart failure
      leading to sudden cardiac death (SCD). Several sarcomeric proteins and modifier
      genes have been implicated in this disease. Troponin I, being a part of the
      Troponin complex (troponin I, troponin C, troponin T), is an important gene for
      sarcomeric function. Four mutations (1 novel) were identified in Indian HCM
      cases, namely, Pro82Ser, Arg98Gln, Arg141Gln and Arg162Gln in Troponin I protein,
      which are in functionally significant domains. In order to analyse the effect of
      the mutations on protein stability and protein-protein interactions within the
      Troponin complex, an in silico study was carried out. The freely available X-ray
      crystal structure (PDB ID: 1JIE) was used as the template to model the protein
      followed by loop generation and development of troponin complex for both the
      troponin I wild type and four mutants (NCBI ID: PRJNA194382). The structural
      study was carried out to determine the effect of mutation on the structural
      stability and protein-protein interactions between three subunits in the complex.
      These mutations, especially the arginine to glutamine substitutions were found to
      result in local perturbations within the troponin complex by creating/removing
      inter/intra molecular hydrogen bonds with troponin T and troponin C. This has led
      to a decrease in the protein stability and loss of important interactions between
      the three subunits. It could have a significant impact on the disease progression
      when coupled with allelic heterogeneity which was observed in the cases carrying
      these mutations. However, this can be further confirmed by functional studies on
      protein levels in the identified cases. 

PMID- 23967089
TI  - Aging, estrogen loss and epoxyeicosatrienoic acids (EETs).
AB  - Inflammation is a key element in many cardiovascular diseases. Both estrogen
      loss, caused by menopause, and aging have inflammatory consequences.
      Epoxyeicosatrienoic acids (EETs) are anti-inflammatory molecules synthesized by
      various cytochrome P450 (Cyp) enzymes from arachidonic acid. EETs are in the
      third (Cytochrome P450) pathway of arachindonic acid metabolism, others being
      cyclooxygenases and lipoxygenases. We hypothesized that aging and estrogen loss
      would reduce levels of anti-inflammatory EETs. Adult (6 mo) and aged (22 mo)
      ovariectomized rats with (OP) and without (Ovx) 17-?-estradiol replacement were
      used in this study. Mass spectrometry was used to measure levels of EETs and
      their metabolites, dihydroxyeicosatrienoic acids (DHETs). Levels of Cyp2C2,
      Cyp2C6, and Cyp2J2, the principal Cyps responsible for EETs synthesis, as well as
      soluble epoxide hydrolase (sEH), which metabolizes EETS to DHETs, were determined
      via western blot. Overall Cyp levels decreased with age, though Cyp2C6 increased
      in the liver. sEH was increased in the kidney with estrogen replacement. Despite
      protein changes, no differences were measured in plasma or aortic tissue levels
      of EETs. However, plasma 14,15 DHET was increased in aged Ovx, and 5,6 DHET in
      adult OP. In conclusion neither aging nor estrogen loss decreased the anti
      inflammatory EETs in the cardiovascular system. 

PMID- 23967090
TI  - Fine-mapping, gene expression and splicing analysis of the disease associated
      LRRK2 locus.
AB  - Association studies have identified several signals at the LRRK2 locus for
      Parkinson's disease (PD), Crohn's disease (CD) and leprosy. However, little is
      known about the molecular mechanisms mediating these effects. To further
      characterize this locus, we fine-mapped the risk association in 5,802 PD and
      5,556 controls using a dense genotyping array (ImmunoChip). Using samples from
      134 post-mortem control adult human brains (UK Human Brain Expression
      Consortium), where up to ten brain regions were available per individual, we
      studied the regional variation, splicing and regulation of LRRK2. We found
      convincing evidence for a common variant PD association located outside of the
      LRRK2 protein coding region (rs117762348, A>G, P = 2.56*10(-8), case/control MAF
      0.083/0.074, odds ratio 0.86 for the minor allele with 95% confidence interval
      [0.80-0.91]). We show that mRNA expression levels are highest in cortical regions
      and lowest in cerebellum. We find an exon quantitative trait locus (QTL) in brain
      samples that localizes to exons 32-33 and investigate the molecular basis of this
      eQTL using RNA-Seq data in n = 8 brain samples. The genotype underlying this eQTL
      is in strong linkage disequilibrium with the CD associated non-synonymous SNP
      rs3761863 (M2397T). We found two additional QTLs in liver and monocyte samples
      but none of these explained the common variant PD association at rs117762348. Our
      results characterize the LRRK2 locus, and highlight the importance and
      difficulties of fine-mapping and integration of multiple datasets to delineate
      pathogenic variants and thus develop an understanding of disease mechanisms. 

PMID- 23967091
TI  - Low-dose paclitaxel ameliorates pulmonary fibrosis by suppressing TGF-beta1/Smad3
      pathway via miR-140 upregulation.
AB  - Abnormal TGF-beta1/Smad3 activation plays an important role in the pathogenesis
      of pulmonary fibrosis, which can be prevented by paclitaxel (PTX). This study
      aimed to investigate an antifibrotic effect of the low-dose PTX (10 to 50 nM in
      vitro, and 0.6 mg/kg in vivo). PTX treatment resulted in phenotype reversion of
      epithelial-mesenchymal transition (EMT) in alveolar epithelial cells (AECs) with
      increase of miR-140. PTX resulted in an amelioration of bleomycin (BLM)-induced
      pulmonary fibrosis in rats with reduction of the wet lung weight to body weight
      ratios and the collagen deposition. Our results further demonstrated that PTX
      inhibited the effect of TGF-beta1 on regulating the expression of Smad3 and
      phosphorylated Smad3 (p-Smad3), and restored the levels of E-cadherin, vimentin
      and alpha-SMA. Moreover, lower miR-140 levels were found in idiopathic pulmonary
      fibrosis (IPF) patients, TGF-beta1-treated AECs and BLM-instilled rat lungs.
      Through decreasing Smad3/p-Smad3 expression and upregulating miR-140, PTX
      treatment could significantly reverse the EMT of AECs and prevent pulmonary
      fibrosis of rats. The action of PTX to ameliorate TGF-beta1-induced EMT was
      promoted by miR-140, which increased E-cadherin levels and reduced the expression
      of vimentin, Smad3 and p-Smad3. Collectively, our results demonstrate that low
      dose PTX prevents pulmonary fibrosis by suppressing the TGF-beta1/Smad3 pathway
      via upregulating miR-140. 

PMID- 23967092
TI  - IVIg treatment reduces catalytic antibody titers of renal transplanted patients.
AB  - Catalytic antibodies are immunoglobulins endowed with enzymatic activity.
      Catalytic IgG has been reported in several human autoimmune and inflammatory
      diseases. In particular, low levels of catalytic IgG have been proposed as a
      prognostic marker for chronic allograft rejection in patients undergoing kidney
      transplant. Kidney allograft is a treatment of choice for patients with end-stage
      renal failure. Intravenous immunoglobulins, a therapeutic pool of human IgG, is
      used in patients with donor-specific antibodies, alone or in conjunction with
      other immunosuppressive treatments, to desensitize the patients and prevent the
      development of acute graft rejection. Here, we followed for a period of 24 months
      the levels of catalytic IgG towards the synthetic peptide Pro-Phe-Arg
      methylcoumarinimide in a large cohort of patients undergoing kidney
      transplantation. Twenty-four percent of the patients received IVIg at the time of
      transplantation. Our results demonstrate a marked reduction in levels of
      catalytic antibodies in all patients three months following kidney transplant.
      The decrease was significantly pronounced in patients receiving adjunct IVIg
      therapy. The results suggests that prevention of acute graft rejection using
      intravenous immunoglobulins induces a transient reduction in the levels of
      catalytic IgG, thus potentially jeopardizing the use of levels of catalytic
      antibodies as a prognosis marker for chronic allograft nephropathy. 

PMID- 23967093
TI  - An inhibition of p38 mitogen activated protein kinase delays the platelet storage
      lesion.
AB  - BACKGROUND AND OBJECTIVES: Platelets during storage undergo diverse alterations
      collectively known as the platelet storage lesion, including metabolic,
      morphological, functional and structural changes. Some changes correlate with
      activation of p38 mitogen activated protein kinase (p38 MAPK). Another MAPK,
      extracellular signal-related kinase (ERK), is involved in PLT activation. The aim
      of this study was to compare the properties of platelets stored in plasma in the
      presence or absence of p38 and ERK MAPK inhibitors. MATERIALS AND METHODS: A
      single Trima apheresis platelet unit (n = 12) was aliquoted into five CLX storage
      bags. Two aliquots were continuously agitated with or without MAPK inhibitors.
      Two aliquots were subjected to 48 hours of interruption of agitation with or
      without MAPK inhibitors. One aliquot contained the same amount of solvent vehicle
      used to deliver the inhibitor. Platelets were stored at 20-24 degrees C for 7
      days and sampled on Days 1, 4, and 7 for 18 in vitro parameters. RESULTS:
      Inhibition of p38 MAPK by VX-702 leads to better maintenance of all platelet in
      vitro storage parameters including platelet mitochondrial function. Accelerated
      by interruption of agitation, the platelet storage lesion of units stored with VX
      702 was diminished to that of platelets stored with continuous agitation.
      Inhibition of ERK MAPK did not ameliorate decrements in any in vitro platelet
      properties. CONCLUSION: Signaling through p38 MAPK, but not ERK, is associated
      with platelet deterioration during storage.

PMID- 23967094
TI  - Socioeconomic, lifestyle and dietary factors associated with dietary supplement
      use during pregnancy.
AB  - BACKGROUND: Information on dietary supplement (DS) use during pregnancy is
      largely lacking. Besides, little is known about the share of DS use as self
      medication versus such use following a physician's advice/prescription. Our aim
      was to evaluate DS use and its socioeconomic, lifestyle and dietary correlates
      among pregnant women participating in the French NutriNet-Sante cohort study.
      METHOD: Data were collected by self-administered web-based questionnaires. Food
      intake was assessed by repeated 24 h dietary records. 903 pregnant women provided
      data on their DS use (both "regular" DS and medication containing mainly
      vitamins/minerals). Supplement users were compared to non-users by unconditional
      logistic regression. RESULTS: DS use-in general and as regards folic acid in
      particular-was positively correlated with age, being primiparous, having higher
      income and belonging to a higher socioprofessional category. DS users had
      significantly higher dietary intakes of most vitamins and minerals. The
      proportion of DS users (e.g., those reporting use at least three days a week)
      increased significantly with the trimester of pregnancy (58.0%, 62.2% and 74.5%,
      respectively). 50.2% of women in their 1st trimester used folic acid. The
      proportion of iron users tripled from the 1st to the 3rd trimester (18.5 to
      63.9%). DS use was prescribed or recommended by a physician in 86.7% of the
      cases. CONCLUSION: This study provided new and detailed information on DS use and
      its correlates during pregnancy. Even in this relatively well-educated
      population, folic acid supplementation at the beginning of pregnancy was
      inadequate and was associated with socioeconomic and demographic disparities.

PMID- 23967095
TI  - Foxo3a expression is a prognostic marker in breast cancer.
AB  - The forkhead box transcription factor Foxo3a has been implicated to play a
      critical role in various cancers by suppressing tumor growth. Recent studies have
      identified Foxo3a as a key regulator of Estrogen Receptor-alpha (ERalpha). In the
      present study, we examined the expression of Foxo3a, and investigated its
      clinical significance and correlation with ER and prognostic role in patients
      with breast cancer. Immunohistochemical analysis was performed on tumors from 70
      breast cancer patients. Interpretable Foxo3a expression was analyzed along with
      major clinicopathologic variables, and a comparison was made with corresponding 5
      year clinical follow-up data. Foxo3a protein expression correlated with ER
      positivity (P<0.001), histologic grade (1, 2) (P = 0.002), axillary lymph node
      negativity (P<0.001) and TNM stage (1, 2) (P<0.001). Moreover, the Kaplan-Meier
      survival curves of the study population showed that a high expression level of
      Foxo3a was significantly correlated with long-term survival (P<0.0001). In a
      multivariate analysis, Foxo3a expression was identified as a favorable
      independent prognostic factor in overall survival (P = 0.038). In conclusion, our
      results indicated that Foxo3a expression is a favorable prognostic marker in
      breast cancer. In addition, Foxo3a staining could potentially be used in patient
      stratification in conjunction with other prognostic markers. 

PMID- 23967096
TI  - Individual foraging strategies reveal niche overlap between endangered galapagos
      pinnipeds.
AB  - Most competition studies between species are conducted from a population-level
      approach. Few studies have examined inter-specific competition in conjunction
      with intra-specific competition, with an individual-based approach. To our
      knowledge, none has been conducted on marine top predators. Sympatric Galapagos
      fur seals (Arctocephalus galapagoensis) and sea lions (Zalophus wollebaeki) share
      similar geographic habitats and potentially compete. We studied their foraging
      niche overlap at Cabo Douglas, Fernandina Island from simultaneously collected
      dive and movement data to examine spatial and temporal inter- and intra-specific
      competition. Sea lions exhibited 3 foraging strategies (shallow, intermediate and
      deep) indicating intra-specific competition. Fur seals exhibited one foraging
      strategy, diving predominantly at night, between 0-80 m depth and mostly at 19-22
      h. Most sea lion dives also occurred at night (63%), between 0-40 m, within fur
      seals' diving depth range. 34% of sea lions night dives occurred at 19-22 h, when
      fur seals dived the most, but most of them occurred at dawn and dusk, when fur
      seals exhibited the least amount of dives. Fur seals and sea lions foraging
      behavior overlapped at 19 and 21 h between 0-30 m depths. Sea lions from the deep
      diving strategy exhibited the greatest foraging overlap with fur seals, in time
      (19 h), depth during overlapping time (21-24 m), and foraging range (37.7%). Fur
      seals foraging range was larger. Cabo Douglas northwest coastal area, region of
      highest diving density, is a foraging "hot spot" for both species. Fur seals and
      sea lions foraging niche overlap occurred, but segregation also occurred; fur
      seals primarily dived at night, while sea lions exhibited night and day diving.
      Both species exploited depths and areas exclusive to their species. Niche breadth
      generally increases with environmental uncertainty and decreased productivity.
      Potential competition between these species could be greater during warmer
      periods when prey availability is reduced. 

PMID- 23967097
TI  - Host species and environmental effects on bacterial communities associated with
      Drosophila in the laboratory and in the natural environment.
AB  - The fruit fly Drosophila is a classic model organism to study adaptation as well
      as the relationship between genetic variation and phenotypes. Although associated
      bacterial communities might be important for many aspects of Drosophila biology,
      knowledge about their diversity, composition, and factors shaping them is
      limited. We used 454-based sequencing of a variable region of the bacterial 16S
      ribosomal RNA gene to characterize the bacterial communities associated with wild
      and laboratory Drosophila isolates. In order to specifically investigate effects
      of food source and host species on bacterial communities, we analyzed samples
      from wild Drosophila melanogaster and D. simulans collected from a variety of
      natural substrates, as well as from adults and larvae of nine laboratory-reared
      Drosophila species. We find no evidence for host species effects in lab-reared
      flies; instead, lab of origin and stochastic effects, which could influence
      studies of Drosophila phenotypes, are pronounced. In contrast, the natural
      Drosophila-associated microbiota appears to be predominantly shaped by food
      substrate with an additional but smaller effect of host species identity. We
      identify a core member of this natural microbiota that belongs to the genus
      Gluconobacter and is common to all wild-caught flies in this study, but absent
      from the laboratory. This makes it a strong candidate for being part of what
      could be a natural D. melanogaster and D. simulans core microbiome. Furthermore,
      we were able to identify candidate pathogens in natural fly isolates. 

PMID- 23967098
TI  - Hepatic parenchymal changes following transcatheter embolization and
      chemoembolization in a rabbit tumor model.
AB  - OBJECTIVE: To compare the effects of transcatheter arterial chemoembolization
      (TACE) with transcatheter arterial embolization (TAE) on liver function, hepatic
      damage, and hepatic fibrogenesis in a rabbit tumor model. MATERIALS AND METHODS:
      Thirty-nine New Zealand white rabbits implanted with VX2 tumors in the left liver
      lobes were randomly divided into three groups: TAE, TACE, and control group. In
      the TAE group (n = 15), polyvinyl alcohol particles (PVAs) were used for left
      hepatic artery embolization. In the TACE group (n = 15), the tumors were treated
      with left hepatic arterial infusions of a suspension of 10-hydroxycamptothecin
      and lipiodol, followed by embolization with PVAs. In the control group (n = 9),
      the animals received sham treatment with distilled water. Serum and liver samples
      were collected at 6 hours, 3 days and 7 days after treatment. Liver damage was
      measured using a liver function test and histological analyses. Liver
      fibrogenesis and hepatic stellate cell (HSC) activation were evaluated using
      Sirius Red and anti-alpha-smooth muscle actin (alpha-SMA) immunohistochemical
      stains. RESULTS: TACE caused liver injury with greater increases in serum alanine
      aminotransferase and aspartate aminotransferase levels on day 3 (P<0.05).
      Histological analyses revealed increased hepatic necrosis in adjacent non
      tumorous liver tissue from day 3 compared to the TAE group (Suzuki score of
      2.33+/-1.29 versus 1.13+/-1.18, P = 0.001). HSC activation and proliferation were
      significantly increased in the TACE group compared to the control group at 3 and
      7 days after treatment (0.074+/-0.014 vs. 0.010+/-0.006, and 0.088+/-0.023 vs.
      0.017+/-0.009, P<0.05). Sirius Red staining demonstrated a statistically
      significant increase in collagen deposition in the livers in the TACE group 7
      days after embolization compared to the control group (0.118+/-0.012 vs. 0.060+/
      0.017, P = 0.05). CONCLUSION: The results of this animal study revealed that TACE
      induced prominent hepatocellular damage and hepatic fibrogenesis, which
      compromised liver function and may be responsible for chronic liver
      decompensation.

PMID- 23967099
TI  - Relating lateralization of eye use to body motion in the avoidance behavior of
      the chameleon (Chamaeleo chameleon).
AB  - Lateralization is mostly analyzed for single traits, but seldom for two or more
      traits while performing a given task (e.g. object manipulation). We examined
      lateralization in eye use and in body motion that co-occur during avoidance
      behaviour of the common chameleon, Chamaeleo chameleon. A chameleon facing a
      moving threat smoothly repositions its body on the side of its perch distal to
      the threat, to minimize its visual exposure. We previously demonstrated that
      during the response (i) eye use and body motion were, each, lateralized at the
      tested group level (N = 26), (ii) in body motion, we observed two similar-sized
      sub-groups, one exhibiting a greater reduction in body exposure to threat
      approaching from the left and one--to threat approaching from the right (left-
      and right-biased subgroups), (iii) the left-biased sub-group exhibited weak
      lateralization of body exposure under binocular threat viewing and none under
      monocular viewing while the right-biased sub-group exhibited strong
      lateralization under both monocular and binocular threat viewing. In avoidance,
      how is eye use related to body motion at the entire group and at the sub-group
      levels? We demonstrate that (i) in the left-biased sub-group, eye use is not
      lateralized, (ii) in the right-biased sub-group, eye use is lateralized under
      binocular, but not monocular viewing of the threat, (iii) the dominance of the
      right-biased sub-group determines the lateralization of the entire group tested.
      We conclude that in chameleons, patterns of lateralization of visual function and
      body motion are inter-related at a subtle level. Presently, the patterns cannot
      be compared with humans' or related to the unique visual system of chameleons,
      with highly independent eye movements, complete optic nerve decussation and
      relatively few inter-hemispheric commissures. We present a model to explain the
      possible inter-hemispheric differences in dominance in chameleons' visual control
      of body motion during avoidance.

PMID- 23967100
TI  - Arginine inhibits adsorption of proteins on polystyrene surface.
AB  - Nonspecific adsorption of protein on solid surfaces causes a reduction of
      concentration as well as enzyme inactivation during purification and storage.
      However, there are no versatile inhibitors of the adsorption between proteins and
      solid surfaces at low concentrations. Therefore, we examined additives for the
      prevention of protein adsorption on polystyrene particles (PS particles) as a
      commonly-used material for vessels such as disposable test tubes and microtubes.
      A protein solution was mixed with PS particles, and then adsorption of protein
      was monitored by the concentration and activity of protein in the supernatant
      after centrifugation. Five different proteins bound to PS particles through
      electrostatic, hydrophobic, and aromatic interactions, causing a decrease in
      protein concentration and loss of enzyme activity in the supernatant. Among the
      additives, including arginine hydrochloride (Arg), lysine hydrochloride,
      guanidine hydrochloride, NaCl, glycine, and glucose, Arg was most effective in
      preventing the binding of proteins to PS particles as well as activity loss.
      Moreover, even after the mixing of protein and PS particles, the addition of Arg
      caused desorption of the bound protein from PS particles. This study demonstrated
      a new function of Arg, which expands the potential for application of Arg to
      proteins. 

PMID- 23967101
TI  - The role of aquaporin and tight junction proteins in the regulation of water
      movement in larval zebrafish (Danio rerio).
AB  - Teleost fish living in freshwater are challenged by passive water influx; however
      the molecular mechanisms regulating water influx in fish are not well understood.
      The potential involvement of aquaporins (AQP) and epithelial tight junction
      proteins in the regulation of transcellular and paracellular water movement was
      investigated in larval zebrafish (Danio rerio). We observed that the half-time
      for saturation of water influx (K(u)) was 4.3+/-0.9 min, and reached equilibrium
      at approximately 30 min. These findings suggest a high turnover rate of water
      between the fish and the environment. Water influx was reduced by the putative
      AQP inhibitor phloretin (100 or 500 MUM). Immunohistochemistry and confocal
      microscopy revealed that AQP1a1 protein was expressed in cells on the yolk sac
      epithelium. A substantial number of these AQP1a1-positive cells were identified
      as ionocytes, either H+-ATPase-rich cells or Na+/K+-ATPase-rich cells. AQP1a1
      appeared to be expressed predominantly on the basolateral membranes of ionocytes,
      suggesting its potential involvement in regulating ionocyte volume and/or water
      flux into the circulation. Additionally, translational gene knockdown of AQP1a1
      protein reduced water influx by approximately 30%, further indicating a role for
      AQP1a1 in facilitating transcellular water uptake. On the other hand, incubation
      with the Ca2+-chelator EDTA or knockdown of the epithelial tight junction protein
      claudin-b significantly increased water influx. These findings indicate that the
      epithelial tight junctions normally act to restrict paracellular water influx.
      Together, the results of the present study provide direct in vivo evidence that
      water movement can occur through transcellular routes (via AQP); the paracellular
      routes may become significant when the paracellular permeability is increased.

PMID- 23967102
TI  - Psychological traces of China's socio-economic reforms in the ultimatum and
      dictator games.
AB  - Can traces of rapid socio-economic changes within a society be reflected in
      experimental games? The post-Mao reforms in China provide a unique natural quasi
      experiment to study people from the same society who were raised with radically
      different values about distribution of wealth and altruistic behavior. We tested
      whether the size of offers in the ultimatum and dictator games are an increasing
      function of the number of years Chinese citizens experienced of the Mao era
      ("planned economy"). For the cohort that lived throughout the entire Mao era, we
      found that mean offers in the two games were substantially higher than what is
      typically offered in laboratory studies. These offers were also higher than those
      of two younger Chinese cohorts. In general, the amount offered decreased with
      less time spent under Mao, while in the oldest group in which every member spent
      the same amount of time under Mao, the younger members tended to offer more,
      suggesting an additional effect of early education under Mao and contradicting
      the alternative hypothesis that generosity increases with age. These results
      suggest that some of the observed individual differences in the offers made in
      experimental games can be traced back to the values of the socio-economic era in
      which individuals grew up. 

PMID- 23967103
TI  - Renal expression of FGF23 in progressive renal disease of diabetes and the effect
      of ACE inhibitor.
AB  - Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone mainly produced by
      bone that acts in the kidney through FGF receptors and Klotho. Here we
      investigated whether the kidney was an additional source of FGF23 during renal
      disease using a model of type 2 diabetic nephropathy. Renal expression of FGF23
      and Klotho was assessed in Zucker diabetic fatty (ZDF) and control lean rats at
      2, 4, 6, 8 months of age. To evaluate whether the renoprotective effect of
      angiotensin converting enzyme (ACE) inhibitor in this model was associated with
      changes in FGF23 and Klotho, ZDF rats received ramipril from 4, when proteinuric,
      to 8 months of age. FGF23 mRNA was not detectable in the kidney of lean rats, nor
      of ZDF rats at 2 months of age. FGF23 became measurable in the kidney of diabetic
      rats at 4 months and significantly increased thereafter. FGF23 protein localized
      in proximal and distal tubules. Renal Klotho mRNA and protein decreased during
      time in ZDF rats. As renal disease progressed, serum phosphate levels increased
      in parallel with decline of fractional phosphorus excretion. Ramipril limited
      proteinuria and renal injury, attenuated renal FGF23 upregulation and ameliorated
      Klotho expression. Ramipril normalized serum phosphate levels and tended to
      increase fractional phosphorus excretion. These data indicate that during
      progressive renal disease the kidney is a site of FGF23 production which is
      limited by ACE inhibition. Interfering pharmacologically with the delicate
      balance of FGF23 and phosphorus in diabetes may have implications in clinics. 

PMID- 23967104
TI  - Assessment of hepatic detoxification activity: proposal of an improved variant of
      the (13)c-methacetin breath test.
AB  - Breath tests based on the administration of a (13)C-labeled drug and subsequent
      monitoring of (13)CO2 in the breath (quantified as DOB - delta over baseline)
      liberated from the drug during hepatic CPY-dependent detoxification are important
      tools in liver function diagnostics. The capability of such breath tests to
      reliably indicate hepatic CYP performance is limited by the fact that (13)CO2 is
      not exclusively exhaled but also exchanged with other compartments of the body.
      In order to assess this bias caused by variations of individual systemic CO2
      kinetics we administered intravenously the test drug (13)C-methacetin to 25
      clinically liver-healthy individuals and monitored progress curves of DOB and the
      plasma concentration of (13)C-methacetin. Applying compartment modelling we
      estimated for each individual a set of kinetic parameters characterizing the time
      dependent exchange of the drug and of CO2 with the liver and non-hepatic body
      compartments. This analysis revealed that individual variations in the kinetics
      of CO2 may account for up to 30% deviation of DOB curve parameters from their
      mean at otherwise identical (13)C-methacetin metabolization rates. In order to
      correct for this bias we introduced a novel detoxification score which ideally
      should be assessed from the DOB curve of a 2-step test ("2DOB") which is
      initialized with the injection of a standard dose of (13)C-labeled bicarbonate
      (in order to provide information on the actual CO2 status of the individual)
      followed by injection of the (13)C-labeled test drug (the common procedure).
      Computer simulations suggest that the predictive power of the proposed 2DOB
      breath test to reliably quantity the CYP-specific hepatic detoxification activity
      should be significantly higher compared to the conventional breath test. 

PMID- 23967105
TI  - Structure, antimicrobial activities and mode of interaction with membranes of
      novel [corrected] phylloseptins from the painted-belly leaf frog, Phyllomedusa
      sauvagii.
AB  - Transcriptomic and peptidomic analysis of skin secretions from the Painted-belly
      leaf frog Phyllomedusa sauvagii led to the identification of 5 novel
      phylloseptins (PLS-S2 to -S6) and also of phylloseptin-1 (PSN-1, here renamed PLS
      S1), the only member of this family previously isolated in this frog. Synthesis
      and characterization of these phylloseptins revealed differences in their
      antimicrobial activities. PLS-S1, -S2, and -S4 (79-95% amino acid sequence
      identity; net charge  = +2) were highly potent and cidal against Gram-positive
      bacteria, including multidrug resistant S. aureus strains, and killed the
      promastigote stage of Leishmania infantum, L. braziliensis and L. major. By
      contrast, PLS-S3 (95% amino acid identity with PLS-S2; net charge  = +1) and -S5
      (net charge  = +2) were found to be almost inactive against bacteria and
      protozoa. PLS-S6 was not studied as this peptide was closely related to PLS-S1.
      Differential scanning calorimetry on anionic and zwitterionic multilamellar
      vesicles combined with circular dichroism spectroscopy and membrane
      permeabilization assays on bacterial cells indicated that PLS-S1, -S2, and -S4
      are structured in an amphipathic alpha-helix that disrupts the acyl chain packing
      of anionic lipid bilayers. As a result, regions of two coexisting phases could be
      formed, one phase rich in peptide and the other lipid-rich. After reaching a
      threshold peptide concentration, the disruption of lipid packing within the
      bilayer may lead to local cracks and disintegration of the microbial membrane.
      Differences in the net charge, alpha-helical folding propensity, and/or degree of
      amphipathicity between PLS-S1, -S2 and -S4, and between PLS-S3 and -S5 appear to
      be responsible for their marked differences in their antimicrobial activities. In
      addition to the detailed characterization of novel phylloseptins from P.
      sauvagii, our study provides additional data on the previously isolated PLS-S1
      and on the mechanism of action of phylloseptins. 

PMID- 23967106
TI  - Indacaterol for chronic obstructive pulmonary disease: systematic review and meta
      analysis.
AB  - BACKGROUND: Inhaled bronchodilators are the first-line therapy for COPD.
      Indacaterol is a novel addition to existing long-acting bronchodilators.
      OBJECTIVES: Systematic review of randomized controlled trials (RCT) ON efficacy
      and safety of indacaterol as compared: 1) with placebo at different dosages, 2)
      with existing bronchodilators; (3) as add-on treatment to tiotropium. METHODS: We
      searched 13 electronic databases, including MEDLINE, EMBASE and CENTRAL, and
      contacted the manufacturer for unpublished data. Primary outcome was mean FEV1
      change at 12(th) week, secondary outcomes included changes in SGRQ, TDI and BODE
      index at 6 months, exacerbation at 1 year, and worsening of symptoms. RESULTS:
      Twelve eligible RCTs of moderate risk of bias included data from 10,977 patients.
      Compared to placebo, indacaterol improved FEV1 by a weighted mean difference
      (WMD) of 0.16 L (95%CI: 0.15, 0.18 L, p<0.001), homogeneously above the minimally
      important difference of 0.10 L. It offered clinically relevant improvement in all
      secondary outcomes except exacerbation. Magnitude of benefit did not differ
      significantly by dosage, but one treatment related death was reported at 300 ug.
      Efficacy of Indacaterol was similar to formoterol and salmeterol (FEV1 WMD = 0.04
      L, 95%CI: 0.01 L, 0.07 L, p = 0.02); and tiotropium (FEV1 WMD = 0.01 L, 95%CI: 
      0.01, 0.03 L, p = 0.61). The use of indacaterol on top of tiotropium yielded
      additional improvement on FEV1 (WMD = 0.07 L, 95%CI: 0.05 L, 0.10 L, p<0.001).
      CONCLUSION: Indacaterol is safe and beneficial for patients with COPD at dosage
      <=150 ug. It may serve as a good alternative to existing bronchodilators, or as
      an add-on to tiotropium for unresponsive patients. Use of higher dosage requires
      further justification.

PMID- 23967107
TI  - Immunohistochemical analysis of retinoblastoma and beta-catenin as an assistant
      tool in the differential diagnosis between Crohn's disease and ulcerative
      colitis.
AB  - In about 10-15% of patients with inflammatory bowel diseases (IBD) there is no
      clear definitive differential diagnosis between Crohn's disease (CD) and
      ulcerative colitis (UC) and the disease is classified as indeterminate colitis.
      Since pharmacological and surgical treatments differ in CD and UC, establishing a
      correct diagnosis is critical. The aim of this work was to access the expression
      profile of proteins involved in colonic inflammation and cancer in samples from
      CD and UC. For that, colon samples from 24 CD, 21 UC and 10 control patients were
      processed for immunohistochemistry using anti-phosphorylated RB at Ser(807/811)
      and anti-beta-catenin. Crypts were blinded, analyzed and counted for
      phosphorylated RB-positive (phospho-RB) cells or scored for positive beta-catenin
      staining. Western blot was used for confirming immuhistochemical results: RB
      phosphorylation was significantly greater in colon samples from patients with CD
      compared with UC (p<0.005). In contrast, the expression of beta-catenin was
      significantly increased in UC compared with CD (p<0.005) samples. Phospho-RB and
      beta-catenin are negatively correlated (CC: -0.573; p = 0.001). A positive
      phospho-RB test yielded high levels of sensitivity, specificity, negative and
      positive predictive values, and accuracy for the diagnosis of CD against UC. This
      work indicates that RB phosphorylation and beta-catenin nuclear translocation are
      differently expressed in CD and UC, and provide novel insights into the
      pathogenic mechanisms of IBD. In particular, rates of phospho-RB-positive cells
      in mucosal samples emerge as a promising tool for the differential diagnosis of
      patients with IBD. 

PMID- 23967108
TI  - Genetic susceptible locus in NOTCH2 interacts with arsenic in drinking water on
      risk of type 2 diabetes.
AB  - BACKGROUND: Chronic exposure to arsenic in drinking water is associated with
      increased risk of type 2 diabetes mellitus (T2DM) but the underlying molecular
      mechanism remains unclear. OBJECTIVES: This study evaluated the interaction
      between single nucleotide polymorphisms (SNPs) in genes associated with diabetes
      and arsenic exposure in drinking water on the risk of developing T2DM. METHODS:
      In 2009-2011, we conducted a follow up study of 957 Bangladeshi adults who
      participated in a case-control study of arsenic-induced skin lesions in 2001
      2003. Logistic regression models were used to evaluate the association between 38
      SNPs in 18 genes and risk of T2DM measured at follow up. T2DM was defined as
      having a blood hemoglobin A1C level greater than or equal to 6.5% at follow-up.
      Arsenic exposure was characterized by drinking water samples collected from
      participants' tubewells. False discovery rates were applied in the analysis to
      control for multiple comparisons. RESULTS: Median arsenic levels in 2001-2003
      were higher among diabetic participants compared with non-diabetic ones (71.6
      ug/L vs. 12.5 ug/L, p-value <0.001). Three SNPs in ADAMTS9 were nominally
      associated with increased risk of T2DM (rs17070905, Odds Ratio (OR)  = 2.30, 95%
      confidence interval (CI) 1.17-4.50; rs17070967, OR = 2.02, 95%CI 1.00-4.06;
      rs6766801, OR = 2.33, 95%CI 1.18-4.60), but these associations did not reach the
      statistical significance after adjusting for multiple comparisons. A significant
      interaction between arsenic and NOTCH2 (rs699780) was observed which
      significantly increased the risk of T2DM (p for interaction = 0.003; q-value =
      0.021). Further restricted analysis among participants exposed to water arsenic
      of less than 148 ug/L showed consistent results for interaction between the
      NOTCH2 variant and arsenic exposure on T2DM (p for interaction  = 0.048; q-value
      = 0.004). CONCLUSIONS: These findings suggest that genetic variation in NOTCH2
      increased susceptibility to T2DM among people exposed to inorganic arsenic.
      Additionally, genetic variants in ADAMTS9 may increase the risk of T2DM.

PMID- 23967109
TI  - Evaluating roles of nodes in optimal allocation of vaccines with economic
      considerations.
AB  - Since the allocation of vaccines is often constrained by limited resources,
      designing an economical vaccination strategy is a fundamental goal of the
      epidemiological modelling. In this study, with the objective of reducing costs,
      we determine the optimal allocation of vaccines for a general class of infectious
      diseases that spread mainly via contact. We use an optimization routine to
      identify the roles of nodes with distinct degrees as depending on the cost of
      treatment to that of vaccination (relative cost of treatment). The optimal
      allocation drives vaccination priority to medium-degree nodes at a low relative
      cost of treatment or to high-degree nodes at a high relative cost of treatment.
      According to the presented results, we may adjust the vaccination priority in the
      face of an endemic situation. 

PMID- 23967110
TI  - The prognostic significance of IRF8 transcripts in adult patients with acute
      myeloid leukemia.
AB  - Interferon regulatory factor 8 (IRF8) is a transcription factor that plays a
      critical role in normal hematopoiesis, such that disruption of IRF8 activity
      promotes leukemogenesis. We and others have identified aberrant expression of
      IRF8 transcripts, including novel splice variants, in acute myeloid leukemia
      (AML), but studies have not investigated the prognostic significance of these
      transcripts. Therefore, we developed and optimized quantitative expression assays
      for both, the wild type, or the reference sequence (WT-IRF8) and novel splice
      variants (SV-IRF8). These assays were used to quantify IRF8 transcript levels in
      194 adult patients with AML, and multivariate analyses investigated the
      prognostic significance of these expression levels. After adjusting for known
      prognostic factors, expression levels of WT- or SV-IRF8 transcripts were not
      significantly associated with complete responses or overall survival. However,
      increased expression of WT-IRF8 was associated with decreased relapse-free
      survival (RFS) in both univariate (P = 0.010) and multivariate (P = 0.019)
      analyses. Similarly, increased expression of SV-IRF8 was associated with a
      decreased RFS (univariate, P = 0.026 and multivariate, P = 0.021). These studies
      show for the first time that WT-IRF8 and SV-IRF8 are independent adverse
      prognostic factors for patients with AML. Additional studies are planned to
      examine the prognostic significance of IRF8 transcripts in other populations of
      AML patients. 

PMID- 23967112
TI  - Remotely sensed rice yield prediction using multi-temporal NDVI data derived from
      NOAA's-AVHRR.
AB  - Grain-yield prediction using remotely sensed data have been intensively studied
      in wheat and maize, but such information is limited in rice, barley, oats and
      soybeans. The present study proposes a new framework for rice-yield prediction,
      which eliminates the influence of the technology development, fertilizer
      application, and management improvement and can be used for the development and
      implementation of provincial rice-yield predictions. The technique requires the
      collection of remotely sensed data over an adequate time frame and a
      corresponding record of the region's crop yields. Longer normalized-difference
      vegetation-index (NDVI) time series are preferable to shorter ones for the
      purposes of rice-yield prediction because the well-contrasted seasons in a longer
      time series provide the opportunity to build regression models with a wide
      application range. A regression analysis of the yield versus the year indicated
      an annual gain in the rice yield of 50 to 128 kg ha(-1). Stepwise regression
      models for the remotely sensed rice-yield predictions have been developed for
      five typical rice-growing provinces in China. The prediction models for the
      remotely sensed rice yield indicated that the influences of the NDVIs on the rice
      yield were always positive. The association between the predicted and observed
      rice yields was highly significant without obvious outliers from 1982 to 2004.
      Independent validation found that the overall relative error is approximately
      5.82%, and a majority of the relative errors were less than 5% in 2005 and 2006,
      depending on the study area. The proposed models can be used in an operational
      context to predict rice yields at the provincial level in China. The
      methodologies described in the present paper can be applied to any crop for which
      a sufficient time series of NDVI data and the corresponding historical yield
      information are available, as long as the historical yield increases
      significantly. 

PMID- 23967111
TI  - Genetic imprint of vaccination on simian/human immunodeficiency virus type 1
      transmitted viral genomes in rhesus macaques.
AB  - Understanding the genetic, antigenic and structural changes that occur during HIV
      1 infection in response to pre-existing immunity will facilitate current efforts
      to develop an HIV-1 vaccine. Much is known about HIV-1 variation at the
      population level but little with regard to specific changes occurring in the
      envelope glycoprotein within a host in response to immune pressure elicited by
      antibodies. The aim of this study was to track and map specific early genetic
      changes occurring in the viral envelope gene following vaccination using a highly
      controlled viral challenge setting in the SHIV macaque model. We generated 449
      full-length env sequences from vaccinees, and 63 from the virus inoculum.
      Analysis revealed a different pattern in the distribution and frequency of
      mutations in the regions of the envelope gene targeted by the vaccine as well as
      different patterns of diversification between animals in the naive control group
      and vaccinees. Given the high stringency of the model it is remarkable that we
      were able to identify genetic changes associated with the vaccination. This work
      provides insight into the characterization of breakthrough viral populations in
      less than fully efficacious vaccines and illustrates the value of HIV-1 Env SHIV
      challenge model in macaques to unravel the mechanisms driving HIV-1 envelope
      genetic diversity in the presence of vaccine induced-responses. 

PMID- 23967113
TI  - Dynamic cerebral autoregulation changes during sub-maximal handgrip maneuver.
AB  - PURPOSE: We investigated the effect of handgrip (HG) maneuver on time-varying
      estimates of dynamic cerebral autoregulation (CA) using the autoregressive moving
      average technique. METHODS: Twelve healthy subjects were recruited to perform HG
      maneuver during 3 minutes with 30% of maximum contraction force. Cerebral blood
      flow velocity, end-tidal CO2 pressure (PETCO2), and noninvasive arterial blood
      pressure (ABP) were continuously recorded during baseline, HG and recovery.
      Critical closing pressure (CrCP), resistance area-product (RAP), and time-varying
      autoregulation index (ARI) were obtained. RESULTS: PETCO2 did not show
      significant changes during HG maneuver. Whilst ABP increased continuously during
      the maneuver, to 27% above its baseline value, CBFV raised to a plateau
      approximately 15% above baseline. This was sustained by a parallel increase in
      RAP, suggestive of myogenic vasoconstriction, and a reduction in CrCP that could
      be associated with metabolic vasodilation. The time-varying ARI index dropped at
      the beginning and end of the maneuver (p<0.005), which could be related to
      corresponding alert reactions or to different time constants of the myogenic,
      metabolic and/or neurogenic mechanisms. CONCLUSION: Changes in dynamic CA during
      HG suggest a complex interplay of regulatory mechanisms during static exercise
      that should be considered when assessing the determinants of cerebral blood flow
      and metabolism.

PMID- 23967114
TI  - Validity of physician billing claims to identify deceased organ donors in large
      healthcare databases.
AB  - OBJECTIVE: We evaluated the validity of physician billing claims to identify
      deceased organ donors in large provincial healthcare databases. METHODS: We
      conducted a population-based retrospective validation study of all deceased
      donors in Ontario, Canada from 2006 to 2011 (n = 988). We included all registered
      deaths during the same period (n = 458,074). Our main outcome measures included
      sensitivity, specificity, positive predictive value, and negative predictive
      value of various algorithms consisting of physician billing claims to identify
      deceased organ donors and organ-specific donors compared to a reference standard
      of medical chart abstraction. RESULTS: The best performing algorithm consisted of
      any one of 10 different physician billing claims. This algorithm had a
      sensitivity of 75.4% (95% CI: 72.6% to 78.0%) and a positive predictive value of
      77.4% (95% CI: 74.7% to 80.0%) for the identification of deceased organ donors.
      As expected, specificity and negative predictive value were near 100%. The number
      of organ donors identified by the algorithm each year was similar to the expected
      value, and this included the pre-validation period (1991 to 2005). Algorithms to
      identify organ-specific donors performed poorly (e.g. sensitivity ranged from 0%
      for small intestine to 67% for heart; positive predictive values ranged from 0%
      for small intestine to 37% for heart). INTERPRETATION: Primary data abstraction
      to identify deceased organ donors should be used whenever possible, particularly
      for the detection of organ-specific donations. The limitations of physician
      billing claims should be considered whenever they are used.

PMID- 23967115
TI  - A new method to isolate and culture rat kupffer cells.
AB  - BACKGROUND: Previous methods for Kupffer cells (KCs) isolation require
      sophisticated skills and tedious procedures. Few studies have attempted to
      explore the self-renewal capacity of KCs in vitro. Therefore, the aim of this
      study was to establish a simple method for rat KCs isolation and further
      investigate the mitotic potential of KCs in vitro. METHODS: KCs were obtained by
      performing one-step perfusion, enzymatic tissue treatment, differential
      centrifugation and selective adherence. The proliferation ability of cultured KCs
      was determined by MTT assay and Propidium Iodide FACS analysis. Phagocytic assay
      and ED-1, ED-2 immunofluorescence were used to identify cell phenotype. After
      stimulation with LPS, the expression of surface antigens (MHCII, CD40, CD80, and
      CD86) and the production of cytokines (NF-kappaB, TNF-alpha, IL-6 and IL-10) were
      measured for cell function identification. RESULTS: KCs were isolated with
      certain numbers and reasonable purities. The KCs were able to survive until at
      least passage 5 (P5), and at P3 showed equally strong phagocytic activity as
      primary KCs (P0). After stimulation with LPS, the change in the expression of
      surface antigens and the production of cytokines for P3 cells was similar to that
      for P0 cells. CONCLUSIONS: Our study provides a simple and efficient method for
      KCs isolation, and reveals that self-renewing KCs have the same phagocytic
      activity and functions as primary KCs.

PMID- 23967116
TI  - Reduction of brain mitochondrial beta-oxidation impairs complex I and V in
      chronic alcohol intake: the underlying mechanism for neurodegeneration.
AB  - Neuropathy and neurocognitive deficits are common among chronic alcohol users,
      which are believed to be associated with mitochondrial dysfunction in the brain.
      The specific type of brain mitochondrial respiratory chain complexes (mRCC) that
      are adversely affected by alcohol abuse has not been studied. Thus, we examined
      the alterations of mRCC in freshly isolated mitochondria from mice brain that
      were pair-fed the ethanol (4% v/v) and control liquid diets for 7-8 weeks. We
      observed that alcohol intake severely reduced the levels of complex I and V. A
      reduction in complex I was associated with a decrease in carnitine
      palmitoyltransferase 1 (cPT1) and cPT2 levels. The mitochondrial outer (cPT1) and
      inner (cPT2) membrane transporter enzymes are specialized in acylation of fatty
      acid from outer to inner membrane of mitochondria for ATP production. Thus, our
      results showed that alterations of cPT1 and cPT2 paralleled a decrease beta
      oxidation of palmitate and ATP production, suggesting that impairment of
      substrate entry step (complex I function) can cause a negative impact on ATP
      production (complex V function). Disruption of cPT1/cPT2 was accompanied by an
      increase in cytochrome C leakage, while reduction of complex I and V paralleled a
      decrease in depolarization of mitochondrial membrane potential (DeltaPsi,
      monitored by JC-1 fluorescence) and ATP production in alcohol intake. We noted
      that acetyl-L-carnitine (ALC, a cofactor of cPT1 and cPT2) prevented the adverse
      effects of alcohol while coenzyme Q10 (CoQ10) was not very effective against
      alcohol insults. These results suggest that understanding the molecular,
      biochemical, and signaling mechanisms of the CNS mitochondrial beta-oxidation
      such as ALC can mitigate alcohol related neurological disorders. 

PMID- 23967117
TI  - A comparison of methods for clustering 16S rRNA sequences into OTUs.
AB  - Recent studies of 16S rRNA sequences through next-generation sequencing have
      revolutionized our understanding of the microbial community composition and
      structure. One common approach in using these data to explore the genetic
      diversity in a microbial community is to cluster the 16S rRNA sequences into
      Operational Taxonomic Units (OTUs) based on sequence similarities. The inferred
      OTUs can then be used to estimate species, diversity, composition, and richness.
      Although a number of methods have been developed and commonly used to cluster the
      sequences into OTUs, relatively little guidance is available on their relative
      performance and the choice of key parameters for each method. In this study, we
      conducted a comprehensive evaluation of ten existing OTU inference methods. We
      found that the appropriate dissimilarity value for defining distinct OTUs is not
      only related with a specific method but also related with the sample complexity.
      For data sets with low complexity, all the algorithms need a higher dissimilarity
      threshold to define OTUs. Some methods, such as, CROP and SLP, are more robust to
      the specific choice of the threshold than other methods, especially for shorter
      reads. For high-complexity data sets, hierarchical cluster methods need a more
      strict dissimilarity threshold to define OTUs because the commonly used
      dissimilarity threshold of 3% often leads to an under-estimation of the number of
      OTUs. In general, hierarchical clustering methods perform better at lower
      dissimilarity thresholds. Our results show that sequence abundance plays an
      important role in OTU inference. We conclude that care is needed to choose both a
      threshold for dissimilarity and abundance for OTU inference. 

PMID- 23967118
TI  - The effect of polyhydroxylated alkaloids on maltase-glucoamylase.
AB  - One of the most important carbohydrate-splitting enzymes is themaltase
      glucoamylase which catalyzes the hydrolysis of alpha-glucosidic linkages. Maltase
      glucoamylase inhibitors during the last few years have aroused medical interests
      in the treatment of diabetes. They contribute to a better understanding of the
      mechanism of maltase-glucoamylase. At present there are many different classes of
      maltase-glucoamylase inhibitors. This paper focuses on alkaloidal inhibitors of
      maltase-glucoamylase and structure-activity relationship (SAR) studies between
      them in order to discover some drugs with better efficiency and lower toxicity
      for treating diabetes. 

PMID- 23967119
TI  - In vivo CD8+ T cell dynamics in the liver of Plasmodium yoelii immunized and
      infected mice.
AB  - Plasmodium falciparum malaria remains one of the most serious health problems
      globally and a protective malaria vaccine is desperately needed. Vaccination with
      attenuated parasites elicits multiple cellular effector mechanisms that lead to
      Plasmodium liver stage elimination. While granule-mediated cytotoxicity requires
      contact between CD8+ effector T cells and infected hepatocytes, cytokine
      secretion should allow parasite killing over longer distances. To better
      understand the mechanism of parasite elimination in vivo, we monitored the
      dynamics of CD8+ T cells in the livers of naive, immunized and sporozoite
      infected mice by intravital microscopy. We found that immunization of BALB/c mice
      with attenuated P. yoelii 17XNL sporozoites significantly increases the velocity
      of CD8+ T cells patrolling the hepatic microvasculature from 2.69+/-0.34 MUm/min
      in naive mice to 5.74+/-0.66 MUm/min, 9.26+/-0.92 MUm/min, and 7.11+/-0.73
      MUm/min in mice immunized with irradiated, early genetically attenuated (Pyuis4
      deficient), and late genetically attenuated (Pyfabb/f-deficient) parasites,
      respectively. Sporozoite infection of immunized mice revealed a 97% and 63%
      reduction in liver stage density and volume, respectively, compared to naive
      controls. To examine cellular mechanisms of immunity in situ, naive mice were
      passively immunized with hepatic or splenic CD8+ T cells. Unexpectedly, adoptive
      transfer rendered the motile CD8+ T cells from immunized mice immotile in the
      liver of P. yoelii infected mice. Similarly, when mice were simultaneously
      inoculated with viable sporozoites and CD8+ T cells, velocities 18 h later were
      also significantly reduced to 0.68+/-0.10 MUm/min, 1.53+/-0.22 MUm/min, and
      1.06+/-0.26 MUm/min for CD8+ T cells from mice immunized with irradiated wild
      type sporozoites, Pyfabb/f-deficient parasites, and P. yoelii CS280-288 peptide,
      respectively. Because immobilized CD8+ T cells are unable to make contact with
      infected hepatocytes, soluble mediators could potentially play a key role in
      parasite elimination under these experimental conditions. 

PMID- 23967120
TI  - Identification of potential Plk1 targets in a cell-cycle specific proteome
      through structural dynamics of kinase and Polo box-mediated interactions.
AB  - Polo like kinase 1 (Plk1) is a key player in orchestrating the wide variety of
      cell-cycle events ranging from centrosome maturation, mitotic entry, checkpoint
      recovery, transcriptional control, spindle assembly, mitotic progression,
      cytokinesis and DNA damage checkpoints recovery. Due to its versatile nature,
      Plk1 is considered an imperative regulator to tightly control the diverse aspects
      of the cell cycle network. Interactions among Plk1 polo box domain (PBD) and its
      putative binding proteins are crucial for the activation of Plk1 kinase domain
      (KD). To date, only a few substrate candidates have been characterized through
      the inclusion of both polo box and kinase domain-mediated interactions. Thus it
      became compelling to explore precise and specific Plk1 substrates through
      reassessment and extension of the structure-function paradigm. To narrow this
      apparently wide gap in knowledge, here we employed a thorough sequence search of
      Plk1 phosphorylation signature containing proteins and explored their structure
      based features like conceptual PBD-binding capabilities and subsequent
      recruitment of KD directed phosphorylation to dissect novel targets of Plk1.
      Collectively, we identified 4,521 phosphodependent proteins sharing similarity to
      the consensus phosphorylation and PBD recognition motifs. Subsequent application
      of filters including similarity index, Gene Ontology enrichment and protein
      localization resulted in stringent pre-filtering of irrelevant candidates and
      isolated unique targets with well-defined roles in cell-cycle machinery and
      carcinogenesis. These candidates were further refined structurally using
      molecular docking and dynamic simulation assays. Overall, our screening approach
      enables the identification of several undefined cell-cycle associated functions
      of Plk1 by uncovering novel phosphorylation targets. 

PMID- 23967121
TI  - A hierarchical coarse-grained (all-atom-to-all-residue) computer simulation
      approach: self-assembly of peptides.
AB  - A hierarchical computational approach (all-atom residue to all-residue peptide)
      is introduced to study self-organizing structures of peptides as a function of
      temperature. A simulated residue-residue interaction involving all-atom
      description, analogous to knowledge-based analysis (with different input), is
      used as an input to a phenomenological coarse-grained interaction for large
      scales computer simulations. A set of short peptides P1 ((1)H (2)S (3)S (4)Y (5)W
      (6)Y (7)A (8)F (9)N (10)N (11)K (12)T) is considered as an example to illustrate
      the utility. We find that peptides assemble rather fast into globular aggregates
      at low temperatures and disperse as random-coil at high temperatures. The
      specificity of the mass distribution of the self-assembly depends on the
      temperature and spatial lengths which are identified from the scaling of the
      structure factor. Analysis of energy and mobility profiles, gyration radius of
      peptide, and radial distribution function of the assembly provide insight into
      the multi-scale (intra- and inter-chain) characteristics. Thermal response of the
      global assembly with the simulated residue-residue interaction is consistent with
      that of the knowledge-based analysis despite expected quantitative differences. 

PMID- 23967122
TI  - Comparative genomic analysis of Brucella melitensis vaccine strain M5 provides
      insights into virulence attenuation.
AB  - The Brucella melitensis vaccine strain M5 is widely used to prevent and control
      brucellosis in animals. In this study, we determined the whole-genome sequence of
      M5, and conducted a comprehensive comparative analysis against the whole-genome
      sequence of the virulent strain 16 M and other reference strains. This analysis
      revealed 11 regions of deletion (RDs) and 2 regions of insertion (RIs) within the
      M5 genome. Among these regions, the sequences encompassed in 5 RDs and 1 RI
      showed consistent variation, with a large deletion between the M5 and the 16 M
      genomes. RD4 and RD5 showed the large diversity among all Brucella genomes, both
      in RD length and RD copy number. Thus, RD4 and RD5 are potential sites for typing
      different Brucella strains. Other RD and RI regions exhibited multiple single
      nucleotide polymorphisms (SNPs). In addition, a genome fragment with a 56 kb
      rearrangement was determined to be consistent with previous studies. Comparative
      genomic analysis indicated that genomic island inversion in Brucella was widely
      present. With the genetic pattern common among all strains analyzed, these 2 RDs,
      1 RI, and one inversion region are potential sites for detection of genomic
      differences. Several SNPs of important virulence-related genes (motB, dhbC, sfuB,
      dsbAB, aidA, aroC, and lysR) were also detected, and may be used to determine the
      mechanism of virulence attenuation. Collectively, this study reveals that
      comparative analysis between wild-type and vaccine strains can provide resources
      for the study of virulence and microevolution of Brucella. 

PMID- 23967123
TI  - Using pattern classification to measure adaptation to the orientation of high
      order aberrations.
AB  - BACKGROUND: The image formed by the eye's optics is blurred by the ocular
      aberrations, specific to each eye. Recent studies demonstrated that the eye is
      adapted to the level of blur produced by the high order aberrations (HOA). We
      examined whether visual coding is also adapted to the orientation of the natural
      HOA of the eye. METHODS AND FINDINGS: Judgments of perceived blur were measured
      in 5 subjects in a psychophysical procedure inspired by the "Classification
      Images" technique. Subjects were presented 500 pairs of images, artificially
      blurred with HOA from 100 real eyes (i.e. different orientations), with total
      blur level adjusted to match the subject's natural blur. Subjects selected the
      image that appeared best focused in each random pair, in a 6-choice ranked
      response. Images were presented through Adaptive Optics correction of the
      subject's aberrations. The images selected as best focused were identified as
      positive, the other as negative responses. The highest classified positive
      responses correlated more with the subject's Point Spread Function, PSF, (r =
      0.47 on average) than the negative (r = 0.34) and the difference was significant
      for all subjects (p<0.02). Using the orientation of the best fitting ellipse of
      angularly averaged integrated PSF intensities (weighted by the subject's
      responses) we found that in 4 subjects the positive PSF response was close to the
      subject's natural PSF orientation (within 21 degrees on average) whereas the
      negative PSF response was almost perpendicularly oriented to the natural PSF (at
      76 degrees on average). CONCLUSIONS: The Classification-Images inspired method is
      very powerful in identifying the internally coded blur of subjects. The
      consistent bias of the Positive PSFs towards the natural PSF in most subjects
      indicates that the internal code of blur appears rather specific to each
      subject's high order aberrations and reveals that the calibration mechanisms for
      normalizing blur also operate using orientation cues.

PMID- 23967124
TI  - A transcription factor contributes to pathogenesis and virulence in Streptococcus
      pneumoniae.
AB  - To date, the role of transcription factors (TFs) in the progression of disease
      for many pathogens is yet to be studied in detail. This is probably due to
      transient, and generally low expression levels of TFs, which are the central
      components controlling the expression of many genes during the course of
      infection. However, a small change in the expression or specificity of a TF can
      radically alter gene expression. In this study, we combined a number of quality
      based selection strategies including structural prediction of modulated genes,
      gene ontology and network analysis, to predict the regulatory mechanisms
      underlying pathogenesis of Streptococcus pneumoniae (the pneumococcus). We have
      identified two TFs (SP_0676 and SP_0927 [SmrC]) that might control tissue
      specific gene expression during pneumococcal translocation from the nasopharynx
      to lungs, to blood and then to brain of mice. Targeted mutagenesis and mouse
      models of infection confirmed the role of SP_0927 in pathogenesis and virulence,
      and suggests that SP_0676 might be essential to pneumococcal viability. These
      findings provide fundamental new insights into virulence gene expression and
      regulation during pathogenesis. 

PMID- 23967125
TI  - The effect of aerobic exercise on intrahepatocellular and intramyocellular lipids
      in healthy subjects.
AB  - BACKGROUND: Intrahepatocellular (IHCL) and intramyocellular (IMCL) lipids are
      ectopic lipid stores. Aerobic exercise results in IMCL utilization in subjects
      over a broad range of exercise capacity. IMCL and IHCL have been related to
      impaired insulin action at the skeletal muscle and hepatic level, respectively.
      The acute effect of aerobic exercise on IHCL is unknown. Possible regulatory
      factors include exercise capacity, insulin sensitivity and fat availability
      subcutaneous and visceral fat mass). AIM: To concomitantly investigate the effect
      of aerobic exercise on IHCL and IMCL in healthy subjects, using Magnetic
      Resonance spectroscopy. METHODS: Normal weight, healthy subjects were included.
      Visit 1 consisted of a determination of VO2max on a treadmill. Visit 2 comprised
      the assessment of hepatic and peripheral insulin sensitivity by a two-step
      hyperinsulinaemic euglycaemic clamp. At Visit 3, subcutaneous and visceral fat
      mass were assessed by whole body MRI, IHCL and IMCL before and after a 2-hours
      aerobic exercise (50% of VO(2max)) using 1H-MR-spectroscopy. RESULTS: Eighteen
      volunteers (12M, 6F) were enrolled in the study (age, 37.6+/-3.2 years, mean+/
      SEM; VO(2max), 53.4+/-2.9 mL/kg/min). Two hours aerobic exercise resulted in a
      significant decrease in IMCL (-22.6+/-3.3, % from baseline) and increase in IHCL
      (+34.9+/-7.6, % from baseline). There was no significant correlation between the
      exercise-induced changes in IMCL and IHCL and exercise capacity, subcutaneous and
      visceral fat mass and hepatic or peripheral insulin sensitivity. CONCLUSIONS:
      IMCL and IHCL are flexible ectopic lipid stores that are acutely influenced by
      physical exercise, albeit in different directions. TRIAL REGISTRATION:
      ClinicalTrial.gov NCT00491582.

PMID- 23967126
TI  - IgA and neutralizing antibodies to influenza a virus in human milk: a randomized
      trial of antenatal influenza immunization.
AB  - BACKGROUND: Antenatal immunization of mothers with influenza vaccine increases
      serum antibodies and reduces the rates of influenza illness in mothers and their
      infants. We report the effect of antenatal immunization on the levels of specific
      anti-influenza IgA levels in human breast milk. (ClinicalTrials.gov identifier
      NCT00142389; http://clinicaltrials.gov/ct2/show/NCT00142389). METHODS AND
      FINDINGS: The Mother's Gift study was a prospective, blinded, randomized
      controlled trial that assigned 340 pregnant Bangladeshi mothers to receive either
      trivalent inactivated influenza vaccine, or 23-valent pneumococcal polysaccharide
      vaccine during the third trimester. We evaluated breast milk at birth, 6 weeks, 6
      months, and 12 months, and serum at 10 weeks and 12 months. Milk and serum
      specimens from 57 subjects were assayed for specific IgA antibody to influenza
      A/New Caledonia (H1N1) using an enzyme-linked immunosorbent assay (ELISA) and a
      virus neutralization assay, and for total IgA using ELISA. Influenza-specific IgA
      levels in breast milk were significantly higher in influenza vaccinees than in
      pneumococcal controls for at least 6 months postpartum (p = 0.04). Geometric mean
      concentrations ranged from 8.0 to 91.1 ELISA units/ml in vaccinees, versus 2.3 to
      13.7 ELISA units/mL in controls. Virus neutralization titers in milk were 1.2 to
      3 fold greater in vaccinees, and correlated with influenza-specific IgA levels (r
      = 0.86). Greater exclusivity of breastfeeding in the first 6 months of life
      significantly decreased the expected number of respiratory illness with fever
      episodes in infants of influenza-vaccinated mothers (p = 0.0042) but not in
      infants of pneumococcal-vaccinated mothers (p = 0.4154). CONCLUSIONS: The
      sustained high levels of actively produced anti-influenza IgA in breast milk and
      the decreased infant episodes of respiratory illness with fever suggest that
      breastfeeding may provide local mucosal protection for the infant for at least 6
      months. Studies are needed to determine the cellular and immunologic mechanisms
      of breast milk-mediated protection after antepartum immunization. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00142389.

PMID- 23967127
TI  - Synucleins antagonize endoplasmic reticulum function to modulate dopamine
      transporter trafficking.
AB  - Synaptic re-uptake of dopamine is dependent on the dopamine transporter (DAT),
      which is regulated by its distribution to the cell surface. DAT trafficking is
      modulated by the Parkinson's disease-linked protein alpha-synuclein, but the
      contribution of synuclein family members beta-synuclein and gamma-synuclein to
      DAT trafficking is not known. Here we use SH-SY5Y cells as a model of DAT
      trafficking to demonstrate that all three synucleins negatively regulate cell
      surface distribution of DAT. Under these conditions the synucleins limit export
      of DAT from the endoplasmic reticulum (ER) by impairment of the ER-Golgi
      transition, leading to accumulation of DAT in this compartment. This mechanism
      for regulating DAT export indirectly through effects on ER and Golgi function
      represents a previously unappreciated role for the extended synuclein family that
      is likely applicable to trafficking of the many proteins that rely on the
      secretory pathway. 

PMID- 23967128
TI  - Toxoplasma gondii protein disulfide isomerase (TgPDI) is a novel vaccine
      candidate against toxoplasmosis.
AB  - Toxoplasma gondii is a ubiquitous protozoan parasite that can infect all warm
      blooded animals, including both mammals and birds. Protein disulfide isomerase
      (PDI) localises to the surface of T. gondii tachyzoites and modulates the
      interactions between parasite and host cells. In this study, the protective
      efficacy of recombinant T. gondii PDI (rTgPDI) as a vaccine candidate against T.
      gondii infection in BALB/c mice was evaluated. rTgPDI was expressed and purified
      from Escherichia coli. Five groups of animals (10 animals/group) were immunised
      with 10, 20, 30, 40 MUg of rTgPDI per mouse or with PBS as a control group. All
      immunisations were performed via the nasal route at 1, 14 and 21 days. Two weeks
      after the last immunisation, the immune responses were evaluated by
      lymphoproliferative assays and by cytokine and antibody measurements. The
      immunised mice were challenged with tachyzoites of the virulent T. gondii RH
      strain on the 14th day after the last immunisation. Following the challenge, the
      tachyzoite loads in tissues were assessed, and animal survival time was recorded.
      Our results showed that the group immunised with 30 MUg rTgPDI showed
      significantly higher levels of specific antibodies against the recombinant
      protein, a strong lymphoproliferative response and significantly higher levels of
      IgG2a, IFN-gamma (IFN-gamma), IL-2 and IL-4 production compared with other doses
      and control groups. While no changes in IL-10 levels were detected. After being
      challenged with T. gondii tachyzoites, the numbers of tachyzoites in brain and
      liver tissues from the rTgPDI group were significantly reduced compared with
      those of the control group, and the survival time of the mice in the rTgPDI group
      was longer than that of mice in the control group. Our results showed that
      immunisation with rTgPDI elicited a protective immune reaction and suggested that
      rTgPDI might represent a promising vaccine candidate for combating toxoplasmosis.

PMID- 23967129
TI  - Fast and flexible: argentine ants recruit from nearby trails.
AB  - Argentine ants (Linepithema humile) live in groups of nests connected by trails
      to each other and to stable food sources. In a field study, we investigated
      whether some ants recruit directly from established, persistent trails to food
      sources, thus accelerating food collection. Our results indicate that Argentine
      ants recruit nestmates to food directly from persistent trails, and that the
      exponential increase in the arrival rate of ants at baits is faster than would be
      possible if recruited ants traveled from distant nests. Once ants find a new food
      source, they walk back and forth between the bait and sometimes share food by
      trophallaxis with nestmates on the trail. Recruiting ants from nearby persistent
      trails creates a dynamic circuit, like those found in other distributed systems,
      which facilitates a quick response to changes in available resources. 

PMID- 23967130
TI  - Gadoxetic acid disodium-enhanced magnetic resonance imaging for the detection of
      hepatocellular carcinoma: a meta-analysis.
AB  - OBJECTIVE: To determine the accuracy of MR imaging with gadoxetic acid disodium
      (Gd-EOB-DTPA) for the detection of hepatocelluar carcinoma (HCC). MATERIALS AND
      METHODS: A systematic search was performed in PUBMED, EMBASE, Web of Science,
      Cochrane Library and the Chinese Biomedical Literature Database up to March 2013
      to identify studies about evaluation of Gd-EOB-DTPA enhanced MR imaging in
      patients suspected of having HCC. The data were extracted to perform
      heterogeneity test and threshold effect test and to calculate sensitivity,
      specificity, diagnostic odds ratio, predictive value, and areas under summary
      receiver operating characteristic curve (AUC). RESULTS: From 601 citations, 10
      were included in the meta-analysis. The methodological quality of the 10 studies
      was good. Overall HCC: There was significant heterogeneity in the pooled analysis
      (I(2) = 69.4%, P = 0.0005), and the pooled weighted values were determined to be
      sensitivity: 0.91 (95% confidence interval (CI): 0.89, 0. 93); specificity: 0.95
      (95% CI: 0.94, 0.96); diagnostic odds ratio: 169.94 (95% CI: 108.84, 265.36);
      positive likelihood ratio: 15.75 (95% CI: 7.45, 33.31); negative likelihood
      ratio: 0.10 (95% CI: 0.06, 0.15). The AUC was 0.9778. HCC in cirrhosis: The
      estimates were to be sensitivity: 0.91 (95% CI: 0.88, 0.93); specificity: 0.93
      (95% CI: 0.89, 0.95); diagnostic odds ratio: 234.24 (95% CI: 33.47, 1639.25);
      positive likelihood ratio: 15.08 (95% CI: 2.20, 103.40); negative likelihood
      ratio: 0.08 (95% CI: 0.03, 0.21). The AUC was 0.9814. <=20 mm HCC: The AUC was
      0.9936. There was no notable publication bias. CONCLUSIONS: This meta-analysis
      suggests that MR imaging with Gd-EOB-DTPA has high diagnostic accuracy for the
      detection of HCC, especially for <=20 mm HCC. This technique shows good prospect
      in diagnosis of HCC.

PMID- 23967131
TI  - Subgraph "backbone" analysis of dynamic brain networks during consciousness and
      anesthesia.
AB  - General anesthesia significantly alters brain network connectivity. Graph
      theoretical analysis has been used extensively to study static brain networks but
      may be limited in the study of rapidly changing brain connectivity during
      induction of or recovery from general anesthesia. Here we introduce a novel
      method to study the temporal evolution of network modules in the brain. We
      recorded multichannel electroencephalograms (EEG) from 18 surgical patients who
      underwent general anesthesia with either propofol (n = 9) or sevoflurane (n = 9).
      Time series data were used to reconstruct networks; each electroencephalographic
      channel was defined as a node and correlated activity between the channels was
      defined as a link. We analyzed the frequency of subgraphs in the network with a
      defined number of links; subgraphs with a high probability of occurrence were
      deemed network "backbones." We analyzed the behavior of network backbones across
      consciousness, anesthetic induction, anesthetic maintenance, and two points of
      recovery. Constitutive, variable and state-specific backbones were identified
      across anesthetic state transitions. Brain networks derived from neurophysiologic
      data can be deconstructed into network backbones that change rapidly across
      states of consciousness. This technique enabled a granular description of network
      evolution over time. The concept of network backbones may facilitate graph
      theoretical analysis of dynamically changing networks. 

PMID- 23967132
TI  - Linguistic diversity and traffic accidents: lessons from statistical studies of
      cultural traits.
AB  - The recent proliferation of digital databases of cultural and linguistic data,
      together with new statistical techniques becoming available has lead to a rise in
      so-called nomothetic studies [1]-[8]. These seek relationships between
      demographic variables and cultural traits from large, cross-cultural datasets.
      The insights from these studies are important for understanding how cultural
      traits evolve. While these studies are fascinating and are good at generating
      testable hypotheses, they may underestimate the probability of finding spurious
      correlations between cultural traits. Here we show that this kind of approach can
      find links between such unlikely cultural traits as traffic accidents, levels of
      extra-martial sex, political collectivism and linguistic diversity. This suggests
      that spurious correlations, due to historical descent, geographic diffusion or
      increased noise-to-signal ratios in large datasets, are much more likely than
      some studies admit. We suggest some criteria for the evaluation of nomothetic
      studies and some practical solutions to the problems. Since some of these studies
      are receiving media attention without a widespread understanding of the
      complexities of the issue, there is a risk that poorly controlled studies could
      affect policy. We hope to contribute towards a general skepticism for
      correlational studies by demonstrating the ease of finding apparently rigorous
      correlations between cultural traits. Despite this, we see well-controlled
      nomothetic studies as useful tools for the development of theories. 

PMID- 23967133
TI  - Bilateral nerve alterations in a unilateral experimental neurotrophic keratopathy
      model: a lateral conjunctival approach for trigeminal axotomy.
AB  - To study bilateral nerve changes in a newly developed novel mouse model for
      neurotrophic keratopathy by approaching the trigeminal nerve from the lateral
      fornix. Surgical axotomy of the ciliary nerve of the trigeminal nerve was
      performed in adult BALB/c mice at the posterior sclera. Axotomized,
      contralateral, and sham-treated corneas were excised on post-operative days 1, 3,
      5, 7 and 14 and immunofluorescence histochemistry was performed with anti-beta
      tubulin antibody to evaluate corneal nerve density. Blink reflex was evaluated
      using a nylon thread. The survival rate was 100% with minimal bleeding during
      axotomy and a surgical time of 8+/-0.5 minutes. The blink reflex was diminished
      at day 1 after axotomy, but remained intact in the contralateral eyes in all
      mice. The central and peripheral subbasal nerves were not detectable in the
      axotomized cornea at day 1 (p<0.001), compared to normal eyes (101.3+/-14.8 and
      69.7+/-12.0 mm/mm2 centrally and peripherally). Interestingly, the subbasal nerve
      density in the contralateral non-surgical eyes also decreased significantly to
      62.4+/-2.8 mm/mm2 in the center from day 1 (p<0.001), but did not change in the
      periphery (77.3+/-11.7 mm/mm2, P = 0.819). Our novel trigeminal axotomy mouse
      model is highly effective, less invasive, rapid, and has a high survival rate,
      demonstrating immediate loss of subbasal nerves in axotomized eyes and decreased
      subbasal nerves in contralateral eyes after unilateral axotomy. This model will
      allow investigating the effects of corneal nerve damage and serves as a new model
      for neurotrophic keratopathy.

PMID- 23967134
TI  - Specific inhibition of the redox activity of ape1/ref-1 by e3330 blocks tnf-alpha
      induced activation of IL-8 production in liver cancer cell lines.
AB  - APE1/Ref-1 is a main regulator of cellular response to oxidative stress via DNA
      repair function and co-activating activity on the NF-kappaB transcription factor.
      APE1 is central in controlling the oxidative stress-based inflammatory processes
      through modulation of cytokines expression and its overexpression is responsible
      for the onset of chemoresistance in different tumors including hepatic cancer. We
      examined the functional role of APE1 overexpression during hepatic cell damage
      related to fatty acid accumulation and the role of the redox function of APE1 in
      the inflammatory process. HepG2 cells were stably transfected with functional and
      non-functional APE1 encoding plasmids and the protective effect of APE1
      overexpression toward genotoxic compounds or FAs accumulation, was tested. JHH6
      cells were stimulated with TNF-alpha in the presence or absence of E3330, an APE1
      redox inhibitor. IL-8 promoter activity was assessed by a luciferase reporter
      assay, gene expression by Real-Time PCR and cytokines (IL-6, IL-8, IL-12) levels
      measured by ELISA. APE1 over-expression did not prevent cytotoxicity induced by
      lipid accumulation. E3330 treatment prevented the functional activation of NF
      kappaB via the alteration of APE1 subcellular trafficking and reduced IL-6 and IL
      8 expression induced by TNF-alpha and FAs accumulation through blockage of the
      redox-mediated activation of NF-kappaB. APE1 overexpression observed in hepatic
      cancer cells may reflect an adaptive response to cell damage and may be
      responsible for further cell resistance to chemotherapy and for the onset of
      inflammatory response. The efficacy of the inhibition of APE1 redox activity in
      blocking TNF-alpha and FAs induced inflammatory response opens new perspectives
      for treatment of inflammatory-based liver diseases. 

PMID- 23967135
TI  - CTA095, a novel Etk and Src dual inhibitor, induces apoptosis in prostate cancer
      cells and overcomes resistance to Src inhibitors.
AB  - Etk is a non-receptor tyrosine kinase, which provides a strong survival signal in
      human prostate cancer cells. Src, another tyrosine kinase that cross-activates
      with Etk, has been shown to play an important role in prostate cancer metastasis.
      Herein, we discovered a new class of Etk inhibitors. Within those inhibitors,
      CTA095 was identified as a potent Etk and Src dual inhibitor. CTA095 was found to
      induce autophagy as well as apoptosis in human prostate cancer cells. In
      addition, CTA095 inhibited HUVEC cell tube formation and "wound healing" of human
      prostate cancer cells, implying its role in inhibition of angiogenesis and
      metastasis of human prostate cancer. More interestingly, CTA095 could overcome
      Src inhibitor resistance in prostate cancer cells. It induces apoptosis in Src
      inhibitor resistant prostate cancer cells, likely through a mechanism of down
      regulation of Myc and BCL2. This finding indicates that simultaneously targeting
      Etk and Src could be a promising approach to overcome drug resistance in prostate
      cancer. 

PMID- 23967136
TI  - Analysis of trafficking, stability and function of human connexin 26 gap junction
      channels with deafness-causing mutations in the fourth transmembrane helix.
AB  - Human Connexin26 gene mutations cause hearing loss. These hereditary mutations
      are the leading cause of childhood deafness worldwide. Mutations in gap junction
      proteins (connexins) can impair intercellular communication by eliminating
      protein synthesis, mis-trafficking, or inducing channels that fail to dock or
      have aberrant function. We previously identified a new class of mutants that form
      non-functional gap junction channels and hemichannels (connexons) by disrupting
      packing and inter-helix interactions. Here we analyzed fourteen point mutations
      in the fourth transmembrane helix of connexin26 (Cx26) that cause non-syndromic
      hearing loss. Eight mutations caused mis-trafficking (K188R, F191L, V198M, S199F,
      G200R, I203K, L205P, T208P). Of the remaining six that formed gap junctions in
      mammalian cells, M195T and A197S formed stable hemichannels after isolation with
      a baculovirus/Sf9 protein purification system, while C202F, I203T, L205V and
      N206S formed hemichannels with varying degrees of instability. The function of
      all six gap junction-forming mutants was further assessed through measurement of
      dye coupling in mammalian cells and junctional conductance in paired Xenopus
      oocytes. Dye coupling between cell pairs was reduced by varying degrees for all
      six mutants. In homotypic oocyte pairings, only A197S induced measurable
      conductance. In heterotypic pairings with wild-type Cx26, five of the six mutants
      formed functional gap junction channels, albeit with reduced efficiency. None of
      the mutants displayed significant alterations in sensitivity to transjunctional
      voltage or induced conductive hemichannels in single oocytes. Intra-hemichannel
      interactions between mutant and wild-type proteins were assessed in rescue
      experiments using baculovirus expression in Sf9 insect cells. Of the four
      unstable mutations (C202F, I203T, L205V, N206S) only C202F and N206S formed
      stable hemichannels when co-expressed with wild-type Cx26. Stable M195T
      hemichannels displayed an increased tendency to aggregate. Thus, mutations in TM4
      cause a range of phenotypes of dysfunctional gap junction channels that are
      discussed within the context of the X-ray crystallographic structure. 

PMID- 23967137
TI  - Preventive effect of dipeptidyl peptidase-4 inhibitor on atherosclerosis is
      mainly attributable to incretin's actions in nondiabetic and diabetic
      apolipoprotein E-null mice.
AB  - AIM: Several recent reports have revealed that dipeptidyl peptidase (DPP)-4
      inhibitors have suppressive effects on atherosclerosis in apolipoprotein E-null
      (Apoe (-/-)) mice. It remains to be seen, however, whether this effect stems from
      increased levels of the two active incretins, glucagon-like peptide-1 (GLP-1) and
      glucose-dependent insulinotropic polypeptide (GIP). METHODS: Nontreated Apoe (-/
      ) mice, streptozotocin-induced diabetic Apoe (-/-) mice, and db/db diabetic mice
      were administered the DPP-4 inhibitor vildagliptin in drinking water and co
      infused with either saline, the GLP-1 receptor blocker, exendin(9-39), the GIP
      receptor blocker, (Pro(3))GIP, or both via osmotic minipumps for 4 weeks. Aortic
      atherosclerosis and oxidized low-density lipoprotein-induced foam cell formation
      in exudate peritoneal macrophages were determined. RESULTS: Vildagliptin
      increased plasma GLP-1 and GIP levels without affecting food intake, body weight,
      blood pressure, or plasma lipid profile in any of the animals tested, though it
      reduced HbA1c in the diabetic mice. Diabetic Apoe (-/-) mice exhibited further
      progressed atherosclerotic lesions and foam cell formation compared with
      nondiabetic counterparts. Nondiabetic and diabetic Apoe (-/-) mice showed a
      comparable response to vildagliptin, namely, remarkable suppression of
      atherosclerotic lesions with macrophage accumulation and foam cell formation in
      peritoneal macrophages. Exendin(9-39) or (Pro(3))GIP partially attenuated the
      vildagliptin-induced suppression of atherosclerosis. The two blockers in
      combination abolished the anti-atherosclerotic effect of vildagliptin in
      nondiabetic mice but only partly attenuated it in diabetic mice. Vildagliptin
      suppressed macrophage foam cell formation in nondiabetic and diabetic mice, and
      this suppressive effect was abolished by infusions with exendin(9
      39)+(Pro(3))GIP. Incubation of DPP-4 or vildagliptin in vitro had no effect on
      macrophage foam cell formation. CONCLUSIONS: Vildagliptin confers a substantial
      anti-atherosclerotic effect in both nondiabetic and diabetic mice, mainly via the
      action of the two incretins. However, the partial attenuation of atherosclerotic
      lesions by the dual incretin receptor antagonists in diabetic mice implies that
      vildagliptin confers a partial anti-atherogenic effect beyond that from the
      incretins.

PMID- 23967138
TI  - Using the electronic medical record to identify community-acquired pneumonia:
      toward a replicable automated strategy.
AB  - BACKGROUND: Timely information about disease severity can be central to the
      detection and management of outbreaks of acute respiratory infections (ARI),
      including influenza. We asked if two resources: 1) free text, and 2) structured
      data from an electronic medical record (EMR) could complement each other to
      identify patients with pneumonia, an ARI severity landmark. METHODS: A manual EMR
      review of 2747 outpatient ARI visits with associated chest imaging identified x
      ray reports that could support the diagnosis of pneumonia (kappa score  = 0.88
      (95% CI 0.82?0.93)), along with attendant cases with Possible Pneumonia (adds
      either cough, sputum, fever/chills/night sweats, dyspnea or pleuritic chest pain)
      or with Pneumonia-in-Plan (adds pneumonia stated as a likely diagnosis by the
      provider). The x-ray reports served as a reference to develop a text classifier
      using machine-learning software that did not require custom coding. To identify
      pneumonia cases, the classifier was combined with EMR-based structured data and
      with text analyses aimed at ARI symptoms in clinical notes. RESULTS: 370
      reference cases with Possible Pneumonia and 250 with Pneumonia-in-Plan were
      identified. The x-ray report text classifier increased the positive predictive
      value of otherwise identical EMR-based case-detection algorithms by 20-70%, while
      retaining sensitivities of 58-75%. These performance gains were independent of
      the case definitions and of whether patients were admitted to the hospital or
      sent home. Text analyses seeking ARI symptoms in clinical notes did not add
      further value. CONCLUSION: Specialized software development is not required for
      automated text analyses to help identify pneumonia patients. These results begin
      to map an efficient, replicable strategy through which EMR data can be used to
      stratify ARI severity.

PMID- 23967139
TI  - Quasispecies analysis of JC virus DNA present in urine of healthy subjects.
AB  - JC virus is a human polyomavirus that infects the majority of people without
      apparent symptoms in healthy subjects and it is the causative agent of
      progressive multifocal leucoencephalopathy (PML), a disorder following lytic
      infection of oligodendrocytes that mainly manifests itself under
      immunosuppressive conditions. A hallmark for JC virus isolated from PML-brain is
      the presence of rearrangements in the non-coding control region (NCCR)
      interspersed between the early and late genes on the viral genome. Such
      rearrangements are believed to originate from the archetype JC virus which is
      shed in urine by healthy subjects and PML patients. We applied next generation
      sequencing to explore the non-coding control region variability in urine of
      healthy subjects in search for JC virus quasispecies and rearrangements
      reminiscent of PML. For 61 viral shedders (out of a total of 254 healthy
      subjects) non-coding control region DNA and VP1 (major capsid protein) coding
      sequences were initially obtained by Sanger sequencing. Deletions between 1 and
      28 nucleotides long appeared in ~24.5% of the NCCR sequences while insertions
      were only detected in ~3.3% of the samples. 454 pyrosequencing was applied on a
      subset of 54 urine samples demonstrating the existence of JC virus quasispecies
      in four subjects (~7.4%). Hence, our results indicate that JC virus DNA in urine
      is not always restricted to one unique virus variant, but can be a mixture of
      naturally occurring variants (quasispecies) reflecting the susceptibility of the
      non-coding control region for genomic rearrangements in healthy individuals. Our
      findings pave the way to explore the presence of viral quasispecies and the
      altered viral tropism that might go along with it as a potential risk factor for
      opportunistic secondary infections such as PML. 

PMID- 23967140
TI  - Red and processed meat intake is associated with higher gastric cancer risk: a
      meta-analysis of epidemiological observational studies.
AB  - BACKGROUND: Red and processed meat was concluded as a limited-suggestive risk
      factor of gastric cancer by the World Cancer Research Fund. However, recent
      epidemiological studies have yielded inconclusive results. METHODS: We searched
      Medline, EMBASE, and the Cochrane Library from their inception to April 2013 for
      both cohort and case-control studies which assessed the association between red
      and/or processed meat intake and gastric cancer risk. Study-specific relative
      risk estimates were polled by random-effect or fixed-effect models. RESULTS:
      Twelve cohort and thirty case-control studies were included in the meta-analysis.
      Significant associations were found between both red (RR: 1.45, 95% CI: 1.22
      1.73) and processed (RR: 1.45, 95% CI: 1.26-1.65) meat intake and gastric cancer
      risk generally. Positive findings were also existed in the items of beef (RR:
      1.28, 95% CI: 1.04-1.57), bacon (RR: 1.37, 95% CI: 1.17-1.61), ham (RR: 1.44, 95%
      CI: 1.00-2.06), and sausage (RR: 1.33, 95% CI: 1.16-1.52). When conducted by
      study design, the association was significant in case-control studies (RR: 1.63,
      95% CI: 1.33-1.99) but not in cohort studies (RR: 1.02, 95% CI: 0.90-1.17) for
      red meat. Increased relative risks were seen in high-quality, adenocarcinoma,
      cardia and European-population studies for red meat. And most subgroup analysis
      confirmed the significant association between processed meat intake and gastric
      cancer risk. CONCLUSIONS: Our findings indicate that consumption of red and/or
      processed meat contributes to increased gastric cancer risk. However, further
      investigation is needed to confirm the association, especially for red meat.

PMID- 23967141
TI  - Genetic variants on 3q21 and in the Sp8 transcription factor gene (SP8) as
      susceptibility loci for psychotic disorders: a genetic association study.
AB  - BACKGROUND: Recent genome-wide association studies (GWASs) investigating bipolar
      disorder (BD) have detected a number of susceptibility genes. These studies have
      also provided novel insight into shared genetic components between BD and
      schizophrenia (SCZ), two major psychotic disorders. To examine the replication of
      the risk variants for BD and the pleiotropic effect of the variants associated
      with BD, we conducted a genetic association study of single nucleotide
      polymorphisms (SNPs) that were selected based upon previous BD GWASs, which
      targeted psychotic disorders (BD and SCZ) in the Japanese population. METHODS:
      Forty-eight SNPs were selected based upon previous GWASs. A two-stage analysis
      was conducted using first-set screening (for all SNPs: BD = 1,012, SCZ = 1,032
      and control = 993) and second-set replication samples (for significant SNPs in
      the screening analysis: BD = 821, SCZ = 1,808 and control = 2,149). We assessed
      allelic association between BD, SCZ, psychosis (BD+SCZ) and the SNPs selected for
      the analysis. RESULTS: Eight SNPs revealed nominal association signals for all
      comparisons (Puncorrected<0.05). Among these SNPs, the top two SNPs (associated
      with psychosis: Pcorrected = 0.048 and 0.037 for rs2251219 and rs2709722,
      respectively) were further assessed in the second-set samples, and we replicated
      the signals from the initial screening analysis (associated with psychosis:
      Pcorrected = 0.0070 and 0.033 for rs2251219 and rs2709722, respectively). The
      meta-analysis between the current and previous GWAS results showed that rs2251219
      in Polybromo1 (PBRM1) was significant on genome-wide association level (P = 5*10(
      8)) only for BD (P = 9.4*10(-9)) and psychosis (P = 2.0*10(-10)). Although the
      association of rs2709722 in Sp8 transcription factor (SP8) was suggestive in the
      Asian population (P = 2.1*10(-7) for psychosis), this signal weakened when the
      samples size was increased by including data from a Caucasian population (P =
      4.3*10(-3)). CONCLUSIONS: We found 3p21.1 (including PBRM1, strong linkage
      disequilibrium made it difficult to pinpoint the risk genes) and SP8 as risk loci
      for BD, SCZ and psychosis. Further replication studies will be required for
      conclusive results.

PMID- 23967142
TI  - The effects of angiotensin II and angiotensin-(1-7) in the rostral ventrolateral
      medulla of rats on stress-induced hypertension.
AB  - We have shown that angiotensin II (Ang II) and angiotensin-(1-7) [Ang-(1-7)]
      increased arterial blood pressure (BP) via glutamate release when microinjected
      into the rostral ventrolateral medulla (RVLM) in normotensive rats (control). In
      the present study, we tested the hypothesis that Ang II and Ang-(1-7) in the RVLM
      are differentially activated in stress-induced hypertension (SIH) by comparing
      the effects of microinjection of Ang II, Ang-(1-7), and their receptor
      antagonists on BP and amino acid release in SIH and control rats. We found that
      Ang II had greater pressor effect, and more excitatory (glutamate) and less
      inhibitory (taurine and gamma-aminobutyric acid) amino acid release in SIH than
      in control animals. Losartan, a selective AT1 receptor (AT1R) antagonist,
      decreased mean BP in SIH but not in control rats. PD123319, a selective AT2
      receptor (AT2R) antagonist, increased mean BP in control but not in SIH rats.
      However, Ang-(1-7) and its selective Mas receptor antagonist Ang779 evoked
      similar effects on BP and amino acid release in both SIH and control rats.
      Furthermore, we found that in the RVLM, AT1R, ACE protein expression (western
      blot) and ACE mRNA (real-time PCR) were significantly higher, whereas AT2R
      protein, ACE2 mRNA and protein expression were significantly lower in SIH than in
      control rats. Mas receptor expression was similar in the two groups. The results
      support our hypothesis and demonstrate that upregulation of Ang II by AT1R, not
      Ang-(1-7), system in the RVLM causes hypertension in SIH rats by increasing
      excitatory and suppressing inhibitory amino acid release.

PMID- 23967143
TI  - Sonic hedgehog protein is decreased and penile morphology is altered in
      prostatectomy and diabetic patients.
AB  - Erectile dysfunction (ED) is a debilitating medical condition and current
      treatments are ineffective in patients with cavernous nerve (CN) injury, due to
      penile remodeling and apoptosis. A critical regulator of penile smooth muscle and
      apoptosis is the secreted protein sonic hedgehog (SHH). SHH protein is decreased
      in rat prostatectomy and diabetic ED models, SHH inhibition in the penis induces
      apoptosis and ED, and SHH treatment at the time of CN injury suppresses smooth
      muscle apoptosis and promotes regeneration of erectile function. Thus SHH
      treatment has significant translational potential as an ED therapy if similar
      mechanisms underlie ED development in patients. In this study we quantify SHH
      protein and morphological changes in corpora cavernosal tissue of control,
      prostatectomy and diabetic patients and hypothesize that decreased SHH protein is
      an underlying cause of ED development in prostatectomy and diabetic patients. Our
      results show significantly decreased SHH protein in prostatectomy and diabetic
      penis. Morphological remodelling of the penis, including significantly increased
      apoptotic index and decreased smooth muscle/collagen ratio, accompanies declining
      SHH. SHH signaling is active in human penis and is altered in a parallel manner
      to previous observations in the rat. These results suggest that SHH has
      significant potential to be developed as an ED therapy in prostatectomy and
      diabetic patients. The increased apoptotic index long after initial injury is
      suggestive of ongoing remodeling that may be clinically manipulatable. 

PMID- 23967144
TI  - The genome of the moderate halophile Amycolicicoccus subflavus DQS3-9A1(T)
      reveals four alkane hydroxylation systems and provides some clues on the genetic
      basis for its adaptation to a petroleum environment.
AB  - The moderate halophile Amycolicicoccus subflavus DQS3-9A1(T) is the type strain
      of a novel species in the recently described novel genus Amycolicicoccus, which
      was isolated from oil mud precipitated from oil produced water. The complete
      genome of A. subflavus DQS3-9A1(T) has been sequenced and is characteristic of
      harboring the genes for adaption to the harsh petroleum environment with
      salinity, high osmotic pressure, and poor nutrient levels. Firstly, it
      characteristically contains four types of alkane hydroxylases, including the
      integral-membrane non-heme iron monooxygenase (AlkB) and cytochrome P450 CYP153,
      a long-chain alkane monooxygenase (LadA) and propane monooxygenase. It also
      accommodates complete pathways for the response to osmotic pressure.
      Physiological tests proved that the strain could grow on n-alkanes ranging from
      C10 to C36 and propane as the sole carbon sources, with the differential
      induction of four kinds of alkane hydroxylase coding genes. In addition, the
      strain could grow in 1-12% NaCl with the putative genes responsible for osmotic
      stresses induced as expected. These results reveal the effective adaptation of
      the strain DQS3-9A1(T) to harsh oil environment and provide a genome platform to
      investigate the global regulation of different alkane metabolisms in bacteria
      that are crucially important for petroleum degradation. To our knowledge, this is
      the first report to describe the co-existence of such four types of alkane
      hydroxylases in a bacterial strain. 

PMID- 23967145
TI  - Quantitative muscle MRI as an assessment tool for monitoring disease progression
      in LGMD2I: a multicentre longitudinal study.
AB  - BACKGROUND: Outcome measures for clinical trials in neuromuscular diseases are
      typically based on physical assessments which are dependent on patient effort,
      combine the effort of different muscle groups, and may not be sensitive to
      progression over short trial periods in slow-progressing diseases. We
      hypothesised that quantitative fat imaging by MRI (Dixon technique) could provide
      more discriminating quantitative, patient-independent measurements of the
      progress of muscle fat replacement within individual muscle groups. OBJECTIVE: To
      determine whether quantitative fat imaging could measure disease progression in a
      cohort of limb-girdle muscular dystrophy 2I (LGMD2I) patients over a 12 month
      period. METHODS: 32 adult patients (17 male;15 female) from 4 European tertiary
      referral centres with the homozygous c.826C>A mutation in the fukutin-related
      protein gene (FKRP) completed baseline and follow up measurements 12 months
      later. Quantitative fat imaging was performed and muscle fat fraction change was
      compared with (i) muscle strength and function assessed using standardized
      physical tests and (ii) standard T1-weighted MRI graded on a 6 point scale.
      RESULTS: There was a significant increase in muscle fat fraction in 9 of the 14
      muscles analyzed using the quantitative MRI technique from baseline to 12 months
      follow up. Changes were not seen in the conventional longitudinal physical
      assessments or in qualitative scoring of the T1w images. CONCLUSIONS:
      Quantitative muscle MRI, using the Dixon technique, could be used as an important
      longitudinal outcome measure to assess muscle pathology and monitor therapeutic
      efficacy in patients with LGMD2I.

PMID- 23967146
TI  - Environmental roots of the late bronze age crisis.
AB  - The Late Bronze Age world of the Eastern Mediterranean, a rich linkage of Aegean,
      Egyptian, Syro-Palestinian, and Hittite civilizations, collapsed famously 3200
      years ago and has remained one of the mysteries of the ancient world since the
      event's retrieval began in the late 19(th) century AD/CE. Iconic Egyptian bas
      reliefs and graphic hieroglyphic and cuneiform texts portray the proximate cause
      of the collapse as the invasions of the "Peoples-of-the-Sea" at the Nile Delta,
      the Turkish coast, and down into the heartlands of Syria and Palestine where
      armies clashed, famine-ravaged cities abandoned, and countrysides depopulated.
      Here we report palaeoclimate data from Cyprus for the Late Bronze Age crisis,
      alongside a radiocarbon-based chronology integrating both archaeological and
      palaeoclimate proxies, which reveal the effects of abrupt climate change-driven
      famine and causal linkage with the Sea People invasions in Cyprus and Syria. The
      statistical analysis of proximate and ultimate features of the sequential
      collapse reveals the relationships of climate-driven famine, sea-borne-invasion,
      region-wide warfare, and politico-economic collapse, in whose wake new societies
      and new ideologies were created. 

PMID- 23967148
TI  - Comparison of magnetic resonance imaging in live vs. post mortem rat brains.
AB  - Magnetic Resonance Imaging (MRI) is an increasingly popular technique for
      examining neurobiology in rodents because it is both noninvasive and
      nondestructive. MRI scans can be acquired from either live or post mortem
      specimens. In vivo scans have a key advantage in that subjects can be scanned at
      multiple time-points in longitudinal studies. However, repeated exposure to
      anesthesia and stress may confound studies. In contrast, post mortem scans offer
      improved image quality and increased signal-to-noise ratio (SNR) due to several
      key advantages: First, the images are not disrupted by motion and pulsation
      artifacts. Second, they allow the brain tissue to be perfused with contrast
      agents, enhancing tissue contrast. Third, they allow longer image acquisition
      times, yielding higher resolution and/or improved SNR. Fourth, they allow
      assessment of groups of animals at the same age without scheduling complications.
      Despite these advantages, researchers are often skeptical of post mortem MRI
      scans because of uncertainty about whether the fixation process alters the MRI
      measurements. To address these concerns, we present a thorough comparative study
      of in vivo and post mortem MRI scans in healthy male Wistar rats at three age
      points throughout adolescence (postnatal days 28 through 80). For each subject,
      an in vivo scan was acquired, followed by perfusion and two post mortem scans at
      two different MRI facilities. The goal was to assess robustness of measurements,
      to detect any changes in volumetric measurements after fixation, and to
      investigate any differential bias that may exist between image acquisition
      techniques. We present this volumetric analysis for comparison of 22 anatomical
      structures between in vivo and post mortem scans. No significant changes in
      volumetric measurements were detected; however, as hypothesized, the image
      quality is dramatically improved in post mortem scans. These findings illustrate
      the validity and utility of using post mortem scans in volumetric neurobiological
      studies. 

PMID- 23967147
TI  - CD36 and Fyn kinase mediate malaria-induced lung endothelial barrier dysfunction
      in mice infected with Plasmodium berghei.
AB  - Severe malaria can trigger acute lung injury characterized by pulmonary edema
      resulting from increased endothelial permeability. However, the mechanism through
      which lung fluid conductance is altered during malaria remains unclear. To define
      the role that the scavenger receptor CD36 may play in mediating this response,
      C57BL/6J (WT) and CD36-/- mice were infected with P. berghei ANKA and monitored
      for changes in pulmonary endothelial barrier function employing an isolated
      perfused lung system. WT lungs demonstrated a >10-fold increase in two measures
      of paracellular fluid conductance and a decrease in the albumin reflection
      coefficient (sigmaalb) compared to control lungs indicating a loss of barrier
      function. In contrast, malaria-infected CD36-/- mice had near normal fluid
      conductance but a similar reduction in sigmaalb. In WT mice, lung sequestered
      iRBCs demonstrated production of reactive oxygen species (ROS). To determine
      whether knockout of CD36 could protect against ROS-induced endothelial barrier
      dysfunction, mouse lung microvascular endothelial monolayers (MLMVEC) from WT and
      CD36-/- mice were exposed to H2O2. Unlike WT monolayers, which showed dose
      dependent decreases in transendothelial electrical resistance (TER) from H2O2
      indicating loss of barrier function, CD36-/- MLMVEC demonstrated dose-dependent
      increases in TER. The differences between responses in WT and CD36-/- endothelial
      cells correlated with important differences in the intracellular
      compartmentalization of the CD36-associated Fyn kinase. Malaria infection
      increased total lung Fyn levels in CD36-/- lungs compared to WT, but this
      increase was due to elevated production of the inactive form of Fyn further
      suggesting a dysregulation of Fyn-mediated signaling. The importance of Fyn in
      CD36-dependent endothelial signaling was confirmed using in vitro Fyn knockdown
      as well as Fyn-/- mice, which were also protected from H2O2- and malaria-induced
      lung endothelial leak, respectively. Our results demonstrate that CD36 and Fyn
      kinase are critical mediators of the increased lung endothelial fluid conductance
      caused by malaria infection. 

PMID- 23967149
TI  - Seasonal phenology and species composition of the aphid fauna in a northern crop
      production area.
AB  - BACKGROUND: The species diversity of aphids and seasonal timing of their flight
      activity can have significant impacts on crop production, as aphid species differ
      in their ability to transmit plant viruses and flight timing affects virus
      epidemiology. The aim of the study was to characterise the species composition
      and phenology of aphid fauna in Finland in one of the northernmost intensive crop
      production areas of the world (latitude 64 degrees ). METHODOLOGY/PRINCIPAL
      FINDINGS: Flight activity was monitored in four growing seasons (2007-010) using
      yellow pan traps (YPTs) placed in 4-8 seed potato fields and a Rothamsted suction
      trap. A total of 58,528 winged aphids were obtained, identified to 83 taxa based
      on morphology, and 34 species were additionally characterised by DNA barcoding.
      Seasonal flight activity patterns analysed based on YPT catch fell into three
      main phenology clusters. Monoecious taxa showed early or middle-season flight
      activity and belonged to species living on shrubs/trees or herbaceous plants,
      respectively. Heteroecious taxa occurred over the entire potato growing season
      (ca. 90 days). Abundance of aphids followed a clear 3-year cycle based on suction
      trap data covering a decade. Rhopalosiphum padi occurring at the end of the
      potato growing season was the most abundant species. The flight activity of Aphis
      fabae, the main vector of Potato virus Y in the region, and Aphis gossypii peaked
      in the beginning of potato growing season. CONCLUSIONS/SIGNIFICANCE: Detailed
      information was obtained on phenology of a large number aphid species, of which
      many are agriculturally important pests acting as vectors of plant viruses. Aphis
      gossypii is known as a pest in greenhouses, but our study shows that it occurs
      also in the field, even far in the north. The novel information on aphid
      phenology and ecology has wide implications for prospective pest management,
      particularly in light of climate change.

PMID- 23967150
TI  - Gray matter abnormalities in schizophrenia patients with tardive dyskinesia: a
      magnetic resonance imaging voxel-based morphometry study.
AB  - OBJECTIVE: The pathophysiological mechanism of TD remains unknown. All previous
      studies, using the region-of-interest method, focused on basal ganglion areas,
      were with inconsistent results. This whole-brain voxel-based morphometry (VBM)
      study investigate the grey matter abnormality of TD and its correlates with
      clinical ratings. METHOD: High resolution T1-weighted brain volumetric MRI from
      25 schizophrenia patients with TD (TD group), 25 age-, gender-, and handedness
      matched schizophrenia patients without TD (non-TD group), and 25 matched healthy
      subjects (NC group) were analyzed using a VBM approach. Clinical ratings included
      the Positive and Negative Symptom Scale (PANSS), Abnormal Involuntary Movement
      Scale (AIMS), and the Simpson-Angus Scale (SAS). RESULTS: The TD group had
      significantly smaller total gray matter volumes than the NC group (p = 0.05).
      Compared to the non-TD group, the TD group had significantly higher PANSS
      negative (p<0.001), SAS (p<0.001), and AIMS (p<0.001) scores; and smaller
      bilateral inferior frontal gyrus, which correlated negatively with the PANSS
      negative scores (r = -0.366, p<0.05); and smaller right superior frontal gyrus,
      which correlated negatively with AIMS scores (r = -0.399, p<0.001), and PANSS
      general score (r = -0.338, p<0.05). LIMITATIONS: The cross-section design can't
      separate the gray matter change to TD from the context of the illness of
      schizophrenia, although TD with more severe clinical psychopathology could be a
      phenotype. CONCLUSIONS: The schizophrenia patients with TD had significantly
      reduced gray matter, mostly at the bilateral inferior frontal gyrus and the right
      superior frontal gyrus, which correlated with severity of clinical symptoms and
      involuntary movement, respectively.

PMID- 23967151
TI  - Meta-analysis of genetic programs between idiopathic pulmonary fibrosis and
      sarcoidosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) and pulmonary sarcoidosis are
      typical interstitial lung diseases with unknown etiology that cause lethal lung
      damages. There are notable differences between these two pulmonary disorders,
      although they do share some similarities. Gene expression profiles have been
      reported independently, but differences on the transcriptional level between
      these two entities have not been investigated. METHODS/RESULTS: All expression
      data of lung tissue samples for IPF and sarcoidosis were from published datasets
      in the Gene Expression Omnibus (GEO) repository. After cross platform
      normalization, the merged sample data were grouped together and were subjected to
      statistical analysis for finding discriminate genes. Gene enrichments with their
      corresponding functions were analyzed by the online analysis engine "Database for
      Annotation, Visualization and Integrated Discovery" (DAVID) 6.7, and genes
      interactions and functional networks were further analyzed by STRING 9.0 and
      Cytoscape 3.0.0 Beta1. One hundred and thirty signature genes could potentially
      differentiate one disease state from another. Compared with normal lung tissue,
      tissue affected by IPF and sarcoidosis displayed similar signatures that
      concentrated on proliferation and differentiation. Distinctly expressed genes
      that could distinguish IPF from sarcoidosis are more enriched in processes of
      cilium biogenesis or degradation and regulating T cell activations. Key
      discriminative network modules involve aspects of bone morphogenetic protein
      receptor two (BMPR2) related and v-myb myeloblastosis viral oncogene (MYB)
      related proliferation. CONCLUSIONS: This study is the first attempt to examine
      the transcriptional regulation of IPF and sarcoidosis across different studies
      based on different working platforms. Groups of significant genes were found to
      clearly distinguish one condition from the other. While IPF and sarcoidosis share
      notable similarities in cell proliferation, differentiation and migration,
      remarkable differences between the diseases were found at the transcription
      level, suggesting that the two diseases are regulated by overlapping yet
      distinctive transcriptional networks.

PMID- 23967152
TI  - Incomplete normalization of regulatory t-cell frequency in the gut mucosa of
      Colombian HIV-infected patients receiving long-term antiretroviral treatment.
AB  - INTRODUCTION: To evaluate the effect of late initiation of HAART and poor immune
      reconstitution on the frequency of regulatory T-cells (Treg) in the peripheral
      blood and gut of HIV-infected patients, we studied Colombian HIV-infected
      patients who had been on suppressive HAART for at least one year. They had
      undetectable viremia but were either immunological responders (HIR); (CD4 counts
      >500 cells/ul) or non-immunological responders (NIR); (CD4 T-cell count <300
      cells/ul). Untreated HIV-infected patients and uninfected controls from the same
      region were also evaluated. METHODS: Frequency and phenotype of regulatory T
      cells (Treg) were analyzed in gut biopsies and blood samples. The functional
      effect of Treg depletion on CMV and HIV responses was determined. Markers of
      immune activation and circulating LPS levels were quantified. RESULTS: Untreated
      patients exhibited high Treg frequency in PBMC and gut, and their Treg express
      high levels of CTLA-4 and PD-1. Although HAART significantly decreased mucosal
      Treg frequency, it did not normalize it in any of the treated groups (HIR and NIR
      patients). Treg normalization was observed in the blood of HIR patients following
      HAART, but did not occur in NIR patients. Treg from HIV-infected patients
      (treated or not) suppressed HIV and hCMV-specific T-cells from gut and blood.
      Plasma LPS levels and percentage of HLA-DR+CD38+ T-cells were significantly
      elevated in all infected groups compared to controls. CONCLUSIONS: These findings
      suggest that control of viral replication is not sufficient to normalize gut Treg
      frequency in patients, independent of their response to HAART. Furthermore,
      persistence of functional Treg in the gut appears to be associated with the
      failure of HAART to repair mucosal damage.

PMID- 23967153
TI  - Grape seed procyanidin reversal of p-glycoprotein associated multi-drug
      resistance via down-regulation of NF-kappaB and MAPK/ERK mediated YB-1 activity
      in A2780/T cells.
AB  - The expression and function of P-glycoprotein (P-gp) is associated with the
      phenotype of multi-drug resistance (MDR), leading chemotherapy failure of
      patients suffered with cancer. Grape seed procyanidin(GSP) is a natural
      polyphenol supplement with anti-inflammatory effect. Present study assessed a new
      use of GSP on the MDR reversal activity and its possible molecular mechanisms in
      MDR1-overpressing paclitaxel resistant ovarian cancer cells. Our results showed
      GSP significantly enhanced the cytotoxicity of paclitaxel and adriamycin in
      paclitaxel resistant A2780/T cells but its parental A2780 cells. Furthermore, GSP
      strongly inhibited P-gp expression by blocking MDR1 gene transcription, as well
      as, increased the intracellular accumulation of the P-gp substrate rhodamine-123
      in A2780/T cells. Nuclear factor-kappaB(NF-kappaB) activity, IkappaB degradation
      level and NF-kappaB/p65 nuclear translocation induced by lipopolysaccharide (LPS)
      and receptor activator for nuclear factor-kappaB ligand (RANKL) were markedly
      inhibited by pre-treatment with GSP. Meanwhile, GSP inhibited MAPK/ERK pathway by
      decreasing the phosphorylation of ERK1/2, resulting in reduced the Y-box binding
      protein 1 (YB-1) activation with blocking its nuclear translocation. Moreover,
      the up-regulation of P-gp expression, the activation of AKT/NF-kappaB and
      MAPK/ERK pathway induced by LPS was attenuated by GSP administration. Compared
      with PDTC and U1026, inhibitor of NF-kappaB and MAPK/ERK respectively, GSP showed
      the same tendency of down-regulating NF-kappaB and MAPK/ERK mediated YB-1
      activities. Thus, GSP reverses P-gp associated MDR by inhibiting the function and
      expression of P-gp through down-regulation of NF-kappaB activity and MAPK/ERK
      pathway mediated YB-1 nuclear translocation, offering insight into the mechanism
      of reversing MDR by natural polyphenol supplement compounds. GSP could be a new
      potential MDR reversal agent used for combination therapy with chemotherapeutics
      in clinic. 

PMID- 23967154
TI  - SNPs altering ammonium transport activity of human Rhesus factors characterized
      by a yeast-based functional assay.
AB  - Proteins of the conserved Mep-Amt-Rh family, including mammalian Rhesus factors,
      mediate transmembrane ammonium transport. Ammonium is an important nitrogen
      source for the biosynthesis of amino acids but is also a metabolic waste product.
      Its disposal in urine plays a critical role in the regulation of the acid/base
      homeostasis, especially with an acid diet, a trait of Western countries. Ammonium
      accumulation above a certain concentration is however pathologic, the
      cytotoxicity causing fatal cerebral paralysis in acute cases. Alteration in
      ammonium transport via human Rh proteins could have clinical outcomes. We used a
      yeast-based expression assay to characterize human Rh variants resulting from non
      synonymous single nucleotide polymorphisms (nsSNPs) with known or unknown
      clinical phenotypes and assessed their ammonium transport efficiency, protein
      level, localization and potential trans-dominant impact. The HsRhAG variants
      (I61R, F65S) associated to overhydrated hereditary stomatocytosis (OHSt), a
      disease affecting erythrocytes, proved affected in intrinsic bidirectional
      ammonium transport. Moreover, this study reveals that the R202C variant of
      HsRhCG, the orthologue of mouse MmRhcg required for optimal urinary ammonium
      excretion and blood pH control, shows an impaired inherent ammonium transport
      activity. Urinary ammonium excretion was RHcg gene-dose dependent in mouse,
      highlighting MmRhcg as a limiting factor. HsRhCG(R202C) may confer susceptibility
      to disorders leading to metabolic acidosis for instance. Finally, the analogous
      R211C mutation in the yeast ScMep2 homologue also impaired intrinsic activity
      consistent with a conserved functional role of the preserved arginine residue.
      The yeast expression assay used here constitutes an inexpensive, fast and easy
      tool to screen nsSNPs reported by high throughput sequencing or individual cases
      for functional alterations in Rh factors revealing potential causal variants. 

PMID- 23967155
TI  - Structural and biophysical characterization of the cytoplasmic domains of human
      BAP29 and BAP31.
AB  - Two members of the B-cell associated 31 (BAP31) family are found in humans; BAP29
      and BAP31. These are ubiquitously expressed receptors residing in the endoplasmic
      reticulum. BAP31 functions in sorting of membrane proteins and in caspase-8
      mediated apoptosis, while BAP29 appears to mainly corroborate with BAP31 in
      sorting. The N-terminal half of these proteins is membrane-bound while the C
      terminal half is cytoplasmic. The latter include the so called variant of death
      effector domain (vDED), which shares weak sequence homology with DED domains.
      Here we present two structures of BAP31 vDED determined from a single and a
      twinned crystal, grown at pH 8.0 and pH 4.2, respectively. These structures show
      that BAP31 vDED forms a dimeric parallel coiled coil with no structural
      similarity to DED domains. Solution studies support this conclusion and strongly
      suggest that an additional alpha-helical domain is present in the C-terminal
      cytoplasmic region, probably forming a second coiled coil. The thermal stability
      of BAP31 vDED is quite modest at neutral pH, suggesting that it may assemble in a
      dynamic fashion in vivo. Surprisingly, BAP29 vDED is partially unfolded at pH 7,
      while a coiled coil is formed at pH 4.2 in vitro. It is however likely that
      folding of the domain is triggered by other factors than low pH in vivo. We found
      no evidence for direct interaction of the cytoplasmic domains of BAP29 and BAP31.

PMID- 23967156
TI  - Transcription factor TFAP2C regulates major programs required for murine fetal
      germ cell maintenance and haploinsufficiency predisposes to teratomas in male
      mice.
AB  - Maintenance and maturation of primordial germ cells is controlled by complex
      genetic and epigenetic cascades, and disturbances in this network lead to either
      infertility or malignant aberration. Transcription factor TFAP2C has been
      described to be essential for primordial germ cell maintenance and to be
      upregulated in several human germ cell cancers. Using global gene expression
      profiling, we identified genes deregulated upon loss of Tfap2c in embryonic stem
      cells and primordial germ cell-like cells. We show that loss of Tfap2c affects
      many aspects of the genetic network regulating germ cell biology, such as
      downregulation of maturation markers and induction of markers indicative for
      somatic differentiation, cell cycle, epigenetic remodeling and pluripotency.
      Chromatin-immunoprecipitation analyses demonstrated binding of TFAP2C to
      regulatory regions of deregulated genes (Sfrp1, Dmrt1, Nanos3, c-Kit, Cdk6,
      Cdkn1a, Fgf4, Klf4, Dnmt3b and Dnmt3l) suggesting that these genes are direct
      transcriptional targets of TFAP2C in primordial germ cells. Since Tfap2c
      deficient primordial germ cell-like cells display cancer related deregulations in
      epigenetic remodeling, cell cycle and pluripotency control, the Tfap2c-knockout
      allele was bred onto 129S2/Sv genetic background. There, mice heterozygous for
      Tfap2c develop with high incidence germ cell cancer resembling human pediatric
      germ cell tumors. Precursor lesions can be observed as early as E16.5 in
      developing testes displaying persisting expression of pluripotency markers. We
      further demonstrate that mice with a heterozygous deletion of the TFAP2C target
      gene Nanos3 are also prone to develop teratomas. These data highlight TFAP2C as a
      critical and dose-sensitive regulator of germ cell fate. 

PMID- 23967158
TI  - Tuberculosis management practices by private practitioners in Andhra Pradesh,
      India.
AB  - SETTING: Private medical practitioners in Visakhapatnam district, Andhra Pradesh,
      India. OBJECTIVES: To evaluate self-reported TB diagnostic and treatment
      practices amongst private medical practitioners against benchmark practices
      articulated in the International Standards of Tuberculosis Care (ISTC), and
      factors associated with compliance with ISTC. DESIGN: Cross- sectional survey
      using semi-structured interviews. RESULTS: Of 296 randomly selected private
      practitioners, 201 (68%) were assessed for compliance to ISTC diagnostic and
      treatment standards in TB management. Only 11 (6%) followed a combination of 6
      diagnostic standards together and only 1 followed a combination of all seven
      treatment standards together. There were 28 (14%) private practitioners who
      complied with a combination of three core ISTC (cough for tuberculosis suspects,
      sputum smear examination and use of standardized treatment). Higher ISTC
      compliance was associated with caring for more than 20 TB patients annually,
      prior sensitization to TB control guidelines, and practice of alternate systems
      of medicine. CONCLUSION: Few private practitioners in Visakhapatnam, India
      reported TB diagnostic and treatment practices that met ISTC. Better engagement
      of the private sector is urgently required to improve TB management practices and
      to prevent diagnostic delay and drug resistance.

PMID- 23967157
TI  - Increased corneal epithelial turnover contributes to abnormal homeostasis in the
      Pax6(+/-) mouse model of aniridia.
AB  - We aimed to test previous predictions that limbal epithelial stem cells (LESCs)
      are quantitatively deficient or qualitatively defective in Pax6(+/-) mice and
      decline with age in wild-type (WT) mice. Consistent with previous studies,
      corneal epithelial stripe patterns coarsened with age in WT mosaics. Mosaic
      patterns were also coarser in Pax6(+/-) mosaics than WT at 15 weeks but not at 3
      weeks, which excludes a developmental explanation and strengthens the prediction
      that Pax6(+/-) mice have a LESC-deficiency. To investigate how Pax6 genotype and
      age affected corneal homeostasis, we compared corneal epithelial cell turnover
      and label-retaining cells (LRCs; putative LESCs) in Pax6(+/-) and WT mice at 15
      and 30 weeks. Limbal BrdU-LRC numbers were not reduced in the older WT mice, so
      this analysis failed to support the predicted age-related decline in slow-cycling
      LESC numbers in WT corneas. Similarly, limbal BrdU-LRC numbers were not reduced
      in Pax6(+/-) heterozygotes but BrdU-LRCs were also present in Pax6(+/-) corneas.
      It seems likely that Pax6(+/-) LRCs are not exclusively stem cells and some may
      be terminally differentiated CD31-positive blood vessel cells, which invade the
      Pax6(+/-) cornea. It was not, therefore, possible to use this approach to test
      the prediction that Pax6(+/-) corneas had fewer LESCs than WT. However, short
      term BrdU labelling showed that basal to suprabasal movement (leading to cell
      loss) occurred more rapidly in Pax6(+/-) than WT mice. This implies that
      epithelial cell loss is higher in Pax6(+/-) mice. If increased corneal epithelial
      cell loss exceeds the cell production capacity it could cause corneal homeostasis
      to become unstable, resulting in progressive corneal deterioration. Although it
      remains unclear whether Pax6(+/-) mice have LESC-deficiency, we suggest that
      features of corneal deterioration, that are often taken as evidence of LESC
      deficiency, might occur in the absence of stem cell deficiency if corneal
      homeostasis is destabilised by excessive cell loss. 

PMID- 23967159
TI  - A meta-analysis of PTGS1 and PTGS2 polymorphisms and NSAID intake on the risk of
      developing cancer.
AB  - BACKGROUND: Several studies have investigated whether the polymorphisms in the
      prostaglandin endoperoxide synthase 1 (PTGS1) and PTGS2 genes and nonsteroidal
      anti-inflammatory drug (NSAID) use are associated with cancer risk; however,
      those studies have produced mixed results. Therefore, we performed a meta
      analysis to evaluate the association between the PTGS1 and PTGS2 polymorphisms
      and the effect of NSAID use on the risk of developing cancer. METHODS: We
      conducted a comprehensive search in PubMed through March 2012. The odds ratios
      (ORs) with the corresponding 95% confidence intervals (CIs) were calculated using
      the fixed-effect model or the random-effect model. RESULTS: The database search
      generated 13 studies that met the inclusion criteria. For PTGS1 rs3842787, NSAID
      users homozygous for the major allele (CC) had a significantly decreased cancer
      risk compared with non-NSAID users (OR = 0.73, 95% CI = 0.59-0.89). For PTGS2
      rs5275 and rs20417, there were no significant differences between the gene
      polymorphism and NSAID use on cancer risk among the 8 and 7 studies,
      respectively. However, in the stratified analysis by the type of cancer or
      ethnicity population, NSAID users homozygous for the major allele (TT) in rs5275
      demonstrated significantly decreased cancer risk compared with non-NSAID users in
      cancer type not involving colorectal adenoma (OR = 0.70, 95% CI = 0.59-0.83) and
      among the USA population (OR = 0.67, 95% CI = 0.56-0.82). NSAID users homozygous
      for the major allele (GG) in rs20417 displayed a significantly decreased cancer
      risk than non-NSAID users among the US population (OR = 0.72, 95% CI = 0.58
      0.88). For the PTGS2 rs689466 and rs2745557 SNPs, there were no significant
      differences. CONCLUSION: This meta-analysis suggests that the associations
      between PTGS polymorphisms and NSAID use on cancer risk may differ with regard to
      the type of cancer and nationality.

PMID- 23967160
TI  - Optimal waist-to-height ratio values for cardiometabolic risk screening in an
      ethnically diverse sample of South African urban and rural school boys and girls.
AB  - BACKGROUND: The proposed waist-to-height ratio (WHtR) cut-off of 0.5 is less
      optimal for cardiometabolic risk screening in children in many settings. The
      purpose of this study was to determine the optimal WHtR for children from South
      Africa, and investigate variations by gender, ethnicity and residence in the
      achieved value. METHODS: Metabolic syndrome (MetS) components were measured in
      1272 randomly selected learners, aged 10-16 years, comprising of 446 black
      Africans, 696 mixed-ancestry and 130 Caucasians. The Youden's index and the
      closest-top-left (CTL) point approaches were used to derive WHtR cut-offs for
      diagnosing any two MetS components, excluding the waist circumference. RESULTS:
      The two approaches yielded similar cut-off in girls, 0.465 (sensitivity 50.0,
      specificity 69.5), but two different values in boys, 0.455 (42.9, 88.4) and 0.425
      (60.3, 67.7) based on the Youden's index and the CTL point, respectively.
      Furthermore, WHtR cut-off values derived differed substantially amongst the
      regions and ethnic groups investigated, whereby the highest cut-off was observed
      in semi-rural and white children, respectively, Youden's index0.505 (31.6, 87.1)
      and CTL point 0.475 (44.4, 75.9). CONCLUSION: The WHtR cut-off of 0.5 is less
      accurate for screening cardiovascular risk in South African children. The optimal
      value in this setting is likely gender and ethnicity-specific and sensitive to
      urbanization.

PMID- 23967162
TI  - Hexosamine biosynthesis is a possible mechanism underlying hypoxia's effects on
      lipid metabolism in human adipocytes.
AB  - INTRODUCTION: Hypoxia regulates adipocyte metabolism. Hexosamine biosynthesis is
      implicated in murine 3T3L1 adipocyte differentiation and is a possible underlying
      mechanism for hypoxia's effects on adipocyte metabolism. METHODS: Lipid
      metabolism was studied in human visceral and subcutaneous adipocytes in in vitro
      hypoxic culture with adipophilic staining, glycerol release, and palmitate
      oxidation assays. Gene expression and hexosamine biosynthesis activation was
      studied with QRTPCR, immunofluorescence microscopy, and Western blotting.
      RESULTS: Hypoxia inhibits lipogenesis and induces basal lipolysis in visceral and
      subcutaneous human adipocytes. Hypoxia induces fatty acid oxidation in visceral
      adipocytes but had no effect on fatty acid oxidation in subcutaneous adipocytes.
      Hypoxia inhibits hexosamine biosynthesis in adipocytes. Inhibition of hexosamine
      biosynthesis with azaserine attenuates lipogenesis and induces lipolysis in
      adipocytes in normoxic conditions, while promotion of hexosamine biosynthesis
      with glucosamine in hypoxic conditions slightly increases lipogenesis.
      CONCLUSIONS: Hypoxia's net effect on human adipocyte lipid metabolism would be
      expected to impair adipocyte buffering capacity and contribute to systemic
      lipotoxicity. Our data suggest that hypoxia may mediate its effects on
      lipogenesis and lipolysis through inhibition of hexosamine biosynthesis.
      Hexosamine biosynthesis represents a target for manipulation of adipocyte
      metabolism.

PMID- 23967161
TI  - Identification and characterization of long non-coding RNAs related to mouse
      embryonic brain development from available transcriptomic data.
AB  - Long non-coding RNAs (lncRNAs) as a key group of non-coding RNAs have gained
      widely attention. Though lncRNAs have been functionally annotated and systematic
      explored in higher mammals, few are under systematical identification and
      annotation. Owing to the expression specificity, known lncRNAs expressed in
      embryonic brain tissues remain still limited. Considering a large number of
      lncRNAs are only transcribed in brain tissues, studies of lncRNAs in
      developmental brain are therefore of special interest. Here, publicly available
      RNA-sequencing (RNA-seq) data in embryonic brain are integrated to identify
      thousands of embryonic brain lncRNAs by a customized pipeline. A significant
      proportion of novel transcripts have not been annotated by available genomic
      resources. The putative embryonic brain lncRNAs are shorter in length, less
      spliced and show less conservation than known genes. The expression of putative
      lncRNAs is in one tenth on average of known coding genes, while comparable with
      known lncRNAs. From chromatin data, putative embryonic brain lncRNAs are
      associated with active chromatin marks, comparable with known lncRNAs. Embryonic
      brain expressed lncRNAs are also indicated to have expression though not evident
      in adult brain. Gene Ontology analysis of putative embryonic brain lncRNAs
      suggests that they are associated with brain development. The putative lncRNAs
      are shown to be related to possible cis-regulatory roles in imprinting even
      themselves are deemed to be imprinted lncRNAs. Re-analysis of one knockdown data
      suggests that four regulators are associated with lncRNAs. Taken together, the
      identification and systematic analysis of putative lncRNAs would provide novel
      insights into uncharacterized mouse non-coding regions and the relationships with
      mammalian embryonic brain development. 

PMID- 23967163
TI  - Elucidation of how cancer cells avoid acidosis through comparative transcriptomic
      data analysis.
AB  - The rapid growth of cancer cells fueled by glycolysis produces large amounts of
      protons in cancer cells, which tri mechanisms to transport them out, hence
      leading to increased acidity in their extracellular environments. It has been
      well established that the increased acidity will induce cell death of normal
      cells but not cancer cells. The main question we address here is: how cancer
      cells deal with the increased acidity to avoid the activation of apoptosis. We
      have carried out a comparative analysis of transcriptomic data of six solid
      cancer types, breast, colon, liver, two lung (adenocarcinoma, squamous cell
      carcinoma) and prostate cancers, and proposed a model of how cancer cells utilize
      a few mechanisms to keep the protons outside of the cells. The model consists of
      a number of previously, well or partially, studied mechanisms for transporting
      out the excess protons, such as through the monocarboxylate transporters, V
      ATPases, NHEs and the one facilitated by carbonic anhydrases. In addition we
      propose a new mechanism that neutralizes protons through the conversion of
      glutamate to gamma-aminobutyrate, which consumes one proton per reaction. We
      hypothesize that these processes are regulated by cancer related conditions such
      as hypoxia and growth factors and by the pH levels, making these encoded
      processes not available to normal cells under acidic conditions. 

PMID- 23967164
TI  - Grouping and crowding affect target appearance over different spatial scales.
AB  - Crowding is the impairment of peripheral target perception by nearby flankers. A
      number of recent studies have shown that crowding shares many features with
      grouping. Here, we investigate whether effects of crowding and grouping on target
      perception are related by asking whether they operate over the same spatial
      scale. A target letter T had two sets of flanking Ts of varying orientations. The
      first set was presented close to the target, yielding strong crowding. The second
      set was either close enough to cause crowding on their own or too far to cause
      crowding on their own. The Ts of the second set had the same orientation that
      either matched the target's orientation (Grouped condition) or not (Ungrouped
      condition). In Experiment 1, the Grouped flankers reduced crowding independently
      of their distance from the target, suggesting that grouping operated over larger
      distances than crowding. In Experiments 2 and 3 we found that grouping did not
      affect sensitivity but produced a strong bias to report that the grouped
      orientation was present at the target location whether or not it was. Finally, we
      investigated whether this bias was a response or perceptual bias, rejecting the
      former in favor of a perceptual grouping explanation. We suggest that the effect
      of grouping is to assimilate the target to the identity of surrounding flankers
      when they are all the same, and that this shape assimilation effect differs in
      its spatial scale from the integration effect of crowding. 

PMID- 23967165
TI  - Contribution of genome-wide association studies to scientific research: a
      pragmatic approach to evaluate their impact.
AB  - The factual value of genome-wide association studies (GWAS) for the understanding
      of multifactorial diseases is a matter of intense debate. Practical consequences
      for the development of more effective therapies do not seem to be around the
      corner. Here we propose a pragmatic and objective evaluation of how much new
      biology is arising from these studies, with particular attention to the
      information that can help prioritize therapeutic targets. We chose multiple
      sclerosis (MS) as a paradigm disease and assumed that, in pre-GWAS candidate-gene
      studies, the knowledge behind the choice of each gene reflected the understanding
      of the disease prior to the advent of GWAS. Importantly, this knowledge was based
      mainly on non-genetic, phenotypic grounds. We performed single-gene and pathway
      oriented comparisons of old and new knowledge in MS by confronting an unbiased
      list of candidate genes in pre-GWAS association studies with those genes
      exceeding the genome-wide significance threshold in GWAS published from 2007 on.
      At the single gene level, the majority (94 out of 125) of GWAS-discovered
      variants had never been contemplated as plausible candidates in pre-GWAS
      association studies. The 31 genes that were present in both pre- and post-GWAS
      lists may be of particular interest in that they represent disease-associated
      variants whose pathogenetic relevance is supported at the phenotypic level (i.e.
      the phenotypic information that steered their selection as candidate genes in pre
      GWAS association studies). As such they represent attractive therapeutic targets.
      Interestingly, our analysis shows that some of these variants are targets of
      pharmacologically active compounds, including drugs that are already registered
      for human use. Compared with the above single-gene analysis, at the pathway level
      GWAS results appear more coherent with previous knowledge, reinforcing some of
      the current views on MS pathogenesis and related therapeutic research. This study
      presents a pragmatic approach that helps interpret and exploit GWAS knowledge. 

PMID- 23967166
TI  - Beneficial impact of CCL2 and CCL12 neutralization on experimental malignant
      pleural effusion.
AB  - Using genetic interventions, we previously determined that C-C motif chemokine
      ligand 2 (CCL2) promotes malignant pleural effusion (MPE) formation in mice. Here
      we conducted preclinical studies aimed at assessing the specific therapeutic
      potential of antibody-mediated CCL2 blockade against MPE. For this, murine MPEs
      or skin tumors were generated in C57BL/6 mice by intrapleural or subcutaneous
      delivery of lung (LLC) or colon (MC38) adenocarcinoma cells. Human lung
      adenocarcinoma cells (A549) were used to induce MPEs in severe combined
      immunodeficient mice. Intraperitoneal antibodies neutralizing mouse CCL2 and/or
      CCL12, a murine CCL2 ortholog, were administered at 10 or 50 mg/kg every three
      days. We found that high doses of CCL2/12 neutralizing antibody treatment (50
      mg/kg) were required to limit MPE formation by LLC cells. CCL2 and CCL12 blockade
      were equally potent inhibitors of MPE development by LLC cells. Combined CCL2 and
      CCL12 neutralization was also effective against MC38-induced MPE and prolonged
      the survival of mice in both syngeneic models. Mouse-specific CCL2-blockade
      limited A549-caused xenogeneic MPE, indicating that host-derived CCL2 also
      contributes to MPE precipitation in mice. The impact of CCL2/12 antagonism was
      associated with inhibition of immune and vascular MPE-related phenomena, such as
      inflammation, new blood vessel assembly and plasma extravasation into the pleural
      space. We conclude that CCL2 and CCL12 blockade are effective against
      experimental MPE induced by murine and human adenocarcinoma in mice. These
      results suggest that CCL2-targeted therapies may hold promise for future use
      against human MPE. 

PMID- 23967167
TI  - Novel three-step pseudo-absence selection technique for improved species
      distribution modelling.
AB  - Pseudo-absence selection for spatial distribution models (SDMs) is the subject of
      ongoing investigation. Numerous techniques continue to be developed, and reports
      of their effectiveness vary. Because the quality of presence and absence data is
      key for acceptable accuracy of correlative SDM predictions, determining an
      appropriate method to characterise pseudo-absences for SDM's is vital. The main
      methods that are currently used to generate pseudo-absence points are: 1)
      randomly generated pseudo-absence locations from background data; 2) pseudo
      absence locations generated within a delimited geographical distance from
      recorded presence points; and 3) pseudo-absence locations selected in areas that
      are environmentally dissimilar from presence points. There is a need for a method
      that considers both geographical extent and environmental requirements to produce
      pseudo-absence points that are spatially and ecologically balanced. We use a
      novel three-step approach that satisfies both spatial and ecological reasons why
      the target species is likely to find a particular geo-location unsuitable. Step 1
      comprises establishing a geographical extent around species presence points from
      which pseudo-absence points are selected based on analyses of environmental
      variable importance at different distances. This step gives an ecologically
      meaningful explanation to the spatial range of background data, as opposed to
      using an arbitrary radius. Step 2 determines locations that are environmentally
      dissimilar to the presence points within the distance specified in step one. Step
      3 performs K-means clustering to reduce the number of potential pseudo-absences
      to the desired set by taking the centroids of clusters in the most
      environmentally dissimilar class identified in step 2. By considering spatial,
      ecological and environmental aspects, the three-step method identifies
      appropriate pseudo-absence points for correlative SDMs. We illustrate this method
      by predicting the New Zealand potential distribution of the Asian tiger mosquito
      (Aedes albopictus) and the Western corn rootworm (Diabrotica virgifera
      virgifera). 

PMID- 23967168
TI  - Association of body mass index with cause specific deaths in Chinese elderly
      hypertensive patients: Minhang community study.
AB  - BACKGROUND: Most studies have suggested that elevated body mass index (BMI) was
      associated with the risk of death from all cause and from specific causes.
      However, there was little evidence illustrating the effect of BMI on the
      mortality in elderly hypertensive patients in Chinese population. METHODS: The
      information of 10,957 hypertensive patients at baseline not less than 60 years
      were from Xinzhuang, a town in Minhang district of Shanghai, was extracted from
      the Electronic Health Record (EHR) system. All study participants were divided
      into eight categories of baseline BMI (with cut-points at 18, 20, 22, 24, 26, 28
      and 30 kg/m(2)). Relative hazard ratio of death from all cause, cardiovascular
      and non-cardiovascular cause by baseline BMI groups were calculated, standardized
      for sex, age, smoking, drinking, physical activity, systolic blood pressure,
      history of cardiovascular disorders, serum lipid disturbance, diabetes mellitus
      and antihypertensive drug treatment. RESULTS: DURING FOLLOW UP (MEDIAN: 3.7
      years), 561 deaths occurred. Underweight (BMI<18 kg/m(2)) was associated with
      significantly increased mortality from all cause mortality (OR: 2.00; 95% CI:
      1.43-2.79) and non cardiovascular mortality (OR: 2.76; 95% CI: 1.87-4.07), but
      not with cardiovascular mortality. For the cause specific analysis, the
      underweight was associated significantly with neoplasms (OR: 2.15; 95% CI: 1.16
      4.00) and respiratory disorders (OR: 3.41; 95% CI: 1.64-7.06). The results for
      total mortality and specific cause mortality were not influenced by sex, age and
      smoking status. CONCLUSION: Our study revealed an association between underweight
      and increased mortality from non-cardiovascular disorders in elderly hypertensive
      patients in Chinese community. Overweight and obesity were not associated with
      all cause or cause specific death.

PMID- 23967169
TI  - Bacterial community development in experimental gingivitis.
AB  - Current knowledge of the microbial composition of dental plaque in early
      gingivitis is based largely on microscopy and cultural methods, which do not
      provide a comprehensive description of oral microbial communities. This study
      used 454-pyrosequencing of the V1-V3 region of 16S rRNA genes (approximately 500
      bp), and bacterial culture, to characterize the composition of plaque during the
      transition from periodontal health to gingivitis. A total of 20 healthy
      volunteers abstained from oral hygiene for two weeks, allowing plaque to
      accumulate and gingivitis to develop. Plaque samples were analyzed at baseline,
      and after one and two weeks. In addition, plaque samples from 20 chronic
      periodontitis patients were analyzed for cross-sectional comparison to the
      experimental gingivitis cohort. All of the healthy volunteers developed
      gingivitis after two weeks. Pyrosequencing yielded a final total of 344,267
      sequences after filtering, with a mean length of 354 bases, that were clustered
      into an average of 299 species-level Operational Taxonomic Units (OTUs) per
      sample. Principal coordinates analysis (PCoA) plots revealed significant shifts
      in the bacterial community structure of plaque as gingivitis was induced, and
      community diversity increased significantly after two weeks. Changes in the
      relative abundance of OTUs during the transition from health to gingivitis were
      correlated to bleeding on probing (BoP) scores and resulted in the identification
      of new health- and gingivitis-associated taxa. Comparison of the healthy
      volunteers to the periodontitis patients also confirmed the association of a
      number of putative periodontal pathogens with chronic periodontitis. Taxa
      associated with gingivitis included Fusobacterium nucleatum subsp. polymorphum,
      Lachnospiraceae [G-2] sp. HOT100, Lautropia sp. HOTA94, and Prevotella oulorum,
      whilst Rothia dentocariosa was associated with periodontal health. Further study
      of these taxa is warranted and may lead to new therapeutic approaches to prevent
      periodontal disease.

PMID- 23967170
TI  - Increased global and local efficiency of human brain anatomical networks detected
      with FLAIR-DTI compared to non-FLAIR-DTI.
AB  - Diffusion-weighted MRI (DW-MRI), the only non-invasive technique for probing
      human brain white matter structures in vivo, has been widely used in both
      fundamental studies and clinical applications. Many studies have utilized
      diffusion tensor imaging (DTI) and tractography approaches to explore the
      topological properties of human brain anatomical networks by using the single
      tensor model, the basic model to quantify DTI indices and tractography. However,
      the conventional DTI technique does not take into account contamination by the
      cerebrospinal fluid (CSF), which has been known to affect the estimated DTI
      measures and tractography in the single tensor model. Previous studies have shown
      that the Fluid-Attenuated Inversion Recovery (FLAIR) technique can suppress the
      contribution of the CSF to the DW-MRI signal. We acquired DTI datasets from
      twenty-two subjects using both FLAIR-DTI and conventional DTI (non-FLAIR-DTI)
      techniques, constructed brain anatomical networks using deterministic
      tractography, and compared the topological properties of the anatomical networks
      derived from the two types of DTI techniques. Although the brain anatomical
      networks derived from both types of DTI datasets showed small-world properties,
      we found that the brain anatomical networks derived from the FLAIR-DTI showed
      significantly increased global and local network efficiency compared with those
      derived from the conventional DTI. The increases in the network regional
      topological properties derived from the FLAIR-DTI technique were observed in CSF
      filled regions, including the postcentral gyrus, periventricular regions,
      inferior frontal and temporal gyri, and regions in the visual cortex. Because
      brain anatomical networks derived from conventional DTI datasets with
      tractography have been widely used in many studies, our findings may have
      important implications for studying human brain anatomical networks derived from
      DW-MRI data and tractography. 

PMID- 23967171
TI  - Reconstituted high-density lipoprotein modulates activation of human leukocytes.
AB  - An anti-inflammatory effect of reconstituted High Density Lipoprotein (rHDL) has
      been demonstrated in atherosclerosis and in sepsis models. An increase of
      adhesion molecules as well as tissue factor expression on endothelial cells in
      response to inflammatory or danger signals are attenuated by the treatment with
      rHDL. Here we show the inhibitory effect of rHDL on the activation of human
      leukocytes in a whole blood assay as well as on monocyte-derived human dendritic
      cells (DC). Multiplex analysis of human whole blood showed that
      phytohaemagglutinin (PHA)-induced secretion of the cytokines IL-1beta, IL-1RA, IL
      2R, IL-6, IL-7, IL-12(p40), IL-15 and IFN-alpha was inhibited. Furthermore, an
      inhibitory effect on the production of the chemokines CCL-2, CCL-4, CCL-5, CXCL-9
      and CXCL-10 was observed. Activation of granulocytes and CD14+ monocytes by PHA
      is inhibited dose-dependently by rHDL shown as decreased up-regulation of ICAM-1
      surface expression. In addition, we found a strong inhibitory effect of rHDL on
      toll-like receptor 2 (TLR2)- and TLR4-mediated maturation of DC. Treatment of DC
      with rHDL prevented the up-regulation of cell surface molecules CD80, CD83 and
      CD86 and it inhibited the TLR-driven activation of inflammatory transcription
      factor NF-kappaB. These findings suggest that rHDL prevents activation of crucial
      cellular players of cellular immunity and could therefore be a useful reagent to
      impede inflammation as well as the link between innate and adaptive immunity.

PMID- 23967172
TI  - Hormone replacement therapy in females can decrease the risk of lung cancer: a
      meta-analysis.
AB  - The purpose of the present meta-analysis was to determine the relationship
      between hormone replacement therapy (HRT) and lung cancer risk in females.
      Publications were reviewed and obtained through a PubMed, EMBASE database and
      Cochrane Library literature search up to May, 2012. The detailed numbers of
      patients in different groups, odd ratios (ORs) and corresponding 95% confidence
      intervals (CIs) were collected and estimated using a random-effects model. Twenty
      five studies entered into the meta-analysis. The total number of participates and
      lung cancer patients was 656,403 and 11,442, respectively. The OR of all 25
      studies was 0.91 (95%CI  = 0.83 to 0.99) and P value was 0.033. In stratified
      analyses, the positive association between HRT use and decreased lung cancer risk
      was also found in the patients with BMI<25 kg/m2 (OR = 0.65, P = 0.000), and
      never smokers patients (OR = 0.86, P = 0.042). However, HRT use in patients with
      artificial menopause could increase the lung cancer risk, OR = 1.51(P = 0.001).
      The result of Egger's test did not show any evidence of publican bias (P =
      0.069). In conclusion, our meta-analysis on HRT and lung cancer risk suggests
      that HRT use is correlated with decreased lung cancer risk in female, especially
      in female with BMI<25 kg/m2 and never smokers.

PMID- 23967173
TI  - Feasibility of image-guided radiotherapy for elderly patients with locally
      advanced rectal cancer.
AB  - PURPOSE: The study aims to assess the tolerance of elderly patients (70 years or
      older) with locally advanced rectal cancers to image-guided radiotherapy (IGRT).
      A retrospective review of 13 elderly patients with locally advanced rectal cancer
      who underwent preoperative chemoradiation using IGRT was performed. Grade 3-4
      acute toxicities, survival, and long-term complications were compared to 17
      younger patients (<70 years) with the same disease stage. RESULTS: Grade 3-4
      hematologic toxicities occurred in 7.6% and 0% (p = 0.4) and gastrointestinal
      toxicities, and, in 15.2% and 5% (p = 0.5), of elderly and younger patients,
      respectively. Surgery was aborted in three patients, two in the elderly group and
      one in the younger group. One patient in the elderly group died after surgery
      from cardiac arrhythmia. After a median follow-up of 34 months, five patients had
      died, two in the elderly and three in the younger group. The 3-year survival was
      90.9% and 87.5% (p = 0.7) for the elderly and younger group respectively. Two
      patients in the younger group developed ischemic colitis and fecal incontinence.
      There was no statistically significant difference in acute and late toxicities as
      well as survival between the two groups. CONCLUSIONS AND CLINICAL RELEVANCE:
      Elderly patients with locally advanced rectal cancers may tolerate preoperative
      chemoradiation with IGRT as well as younger patients. Further prospective studies
      should be performed to investigate the potential of IGRT for possible cure in
      elderly patients with locally advanced rectal cancer.

PMID- 23967174
TI  - Higher levels of neutralizing antibodies against KSHV in KS patients compared to
      asymptomatic individuals from Zambia.
AB  - Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi
      Sarcoma (KS), the most common cancer diagnosed in HIV- infected patients. The
      role of neutralizing antibodies in KS pathogenesis and in KSHV infected
      individuals is not clearly understood. The goal of this study was to investigate
      and compare the prevalence and titers of neutralizing antibodies in plasma
      samples from KS patients and KSHV infected asymptomatic individuals from Zambia,
      a KS endemic region in sub-Saharan Africa. Plasma samples (N = 267) consisting of
      KS patients (group 1) and asymptomatic individuals (group 2) were collected from
      Lusaka, Zambia. A flow cytometry based quantitative neutralization assay
      utilizing recombinant KSHV expressing GFP was used to detect KSHV neutralizing
      antibodies. Our results show that the overall prevalence of neutralizing
      antibodies in KS patients (group 1) was 66.7% which was significantly higher than
      the prevalence of 6.5% present in KSHV infected asymptomatic individuals (group
      2). Total antibody titers as well as neutralizing antibodies titers were found to
      be significantly higher among KS patients. It is likely that higher neutralizing
      antibodies prevalence and titers in KS patients result from higher levels of
      antigenic stimulation over time. This study is first to compare prevalence and
      titers of neutralizing antibodies in participants with and without disease from a
      KSHV endemic region. 

PMID- 23967175
TI  - The 18-kDa translocator protein (TSPO) disrupts mammary epithelial morphogenesis
      and promotes breast cancer cell migration.
AB  - Mitochondria play important roles in cancer progression and have emerged as
      viable targets for cancer therapy. Increasing levels of the outer mitochondrial
      membrane protein, 18-kDa translocator protein (TSPO), are associated with
      advancing breast cancer stage. In particular, higher TSPO levels are found in
      estrogen receptor (ER)-negative breast tumors, compared with ER-positive tumors.
      In this study, we sought to define the roles of TSPO in the acquisition of breast
      cancer malignancy. Using a three-dimensional Matrigel culture system, we
      determined the impact of elevated TSPO levels on mammary epithelial
      morphogenesis. Our studies demonstrate that stable overexpression of TSPO in
      mammary epithelial MCF10A acini drives proliferation and provides partial
      resistance to luminal apoptosis, resulting in enlarged acinar structures with
      partially filled lumen that resemble early stage breast lesions leading to breast
      cancer. In breast cancer cell lines, TSPO silencing or TSPO overexpression
      significantly altered the migratory activity. In addition, we found that
      combination treatment with the TSPO ligands (PK 11195 or Ro5-4864) and
      lonidamine, a clinical phase II drug targeting mitochondria, decreased viability
      of ER-negative breast cancer cell lines. Taken together, these data demonstrate
      that increases in TSPO levels at different stages of breast cancer progression
      results in the acquisition of distinct properties associated with malignancy.
      Furthermore, targeting TSPO, particularly in combination with other mitochondria
      targeting agents, may prove useful for the treatment of ER-negative breast
      cancer. 

PMID- 23967176
TI  - Microarray-based genotyping and clinical outcomes of Staphylococcus aureus
      bloodstream infection: an exploratory study.
AB  - The clinical course of Staphylococcus aureus bacteremia varies extensively. We
      sought to determine the relationship between genetic characteristics of the
      infecting pathogen and clinical outcomes in an exploratory study. In two study
      centers, 317 blood culture isolates were analyzed by DNA microarray and spa
      genotyping. By uni- and multivariate regression analyses associations of genotype
      data with 30-day all-cause mortality, severe sepsis/septic shock, disseminated
      disease, endocarditis, and osteoarticular infection were investigated. Univariate
      analysis showed significant association between S. aureus genes/gene-clusters or
      clonal complexes and clinical endpoints. For example CC15 was associated with 30
      day mortality and CC22 with osteoarticular infection. In multivariate analysis
      methicillin resistance (mecA, OR 4.8 [1.43-16.06]) and the beta-lactamase-gene
      (bla, OR 3.12 [1.17-8.30]) remained independently associated with 30-day
      mortality. The presence of genes for enterotoxins (sed/sej/ser) was associated
      with endocarditis (OR 5.11 [1.14-18.62]). Host factors such as McCabe
      classification (OR 4.52 [2.09-9.79] for mortality), age (OR 1.06 [1.03-1.10] per
      year), and community-acquisition (OR 3.40 [1.31-8.81]) had a major influence on
      disease severity, dissemination and mortality. Individual genotypes and clonal
      complexes of S. aureus can only partially explain clinical features and outcomes
      of S. aureus bacteremia. Genotype-phenotype association studies need to include
      adjustments for host factors like age, comorbidity and community-acquisition. 

PMID- 23967177
TI  - The FLT3 inhibitor quizartinib inhibits ABCG2 at pharmacologically relevant
      concentrations, with implications for both chemosensitization and adverse drug
      interactions.
AB  - The oral second-generation bis-aryl urea fms-like tyrosine kinase 3 (FLT3)
      inhibitor quizartinib (AC220) has favorable kinase selectivity and
      pharmacokinetics. It inhibits mutant and wild-type FLT3 in vivo at 0.1 and 0.5
      uM, respectively, and has shown favorable activity and tolerability in phase I
      and II trials in acute myeloid leukemia, with QT prolongation as the dose
      limiting toxicity. Co-administration with chemotherapy is planned. We
      characterized interactions of quizartinib with the ATP-binding cassette (ABC)
      proteins ABCB1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein). Its
      effects on uptake of fluorescent substrates and apoptosis were measured by flow
      cytometry, binding to ABCB1 and ABCG2 drug-binding sites by effects on
      [125I]iodoarylazidoprazosin ([125I]-IAAP) photolabeling and ATPase activity, and
      cell viability by the WST-1 colorimetric assay. Quizartinib inhibited transport
      of fluorescent ABCG2 and ABCB1 substrates in ABCG2- and ABCB1-overexpressing
      cells in a concentration-dependent manner, from 0.1 to 5 uM and from 0.5 to 10
      uM, respectively, and inhibited [125I]-IAAP photolabeling of ABCG2 and ABCB1 with
      IC50 values of 0.07 and 3.3 uM, respectively. Quizartinib at higher
      concentrations decreased ABCG2, but not ABCB1, ATPase activity. Co-incubation
      with quizartinib at 0.1 to 1 uM sensitized ABCG2-overexpressing K562/ABCG2 and
      8226/MR20 cells to ABCG2 substrate chemotherapy drugs in a concentration
      dependent manner in cell viability and apoptosis assays. Additionally,
      quizartinib increased cellular uptake of the ABCG2 substrate fluoroquinolone
      antibiotic ciprofloxacin, which also prolongs the QT interval, in a concentration
      dependent manner, predicting altered ciprofloxacin pharmacokinetics and
      pharmacodynamics when co-administered with quizartinib. Thus quizartinib inhibits
      ABCG2 at pharmacologically relevant concentrations, with implications for both
      chemosensitization and adverse drug interactions. These interactions should be
      considered in the design of treatment regimens combining quizartinib and
      chemotherapy drugs and in choice of concomitant medications to be administered
      with quizartinib.

PMID- 23967178
TI  - Differential post-surgical metastasis and survival in SCID, NOD-SCID and NOD-SCID
      IL-2Rgamma(null) mice with parental and subline variants of human breast cancer:
      implications for host defense mechanisms regulating metastasis.
AB  - We compare for the first time, the metastatic aggressiveness of the parental MDA
      MB-231 breast cancer cell line and two luciferase-tagged in vivo-derived and
      selected pro-metastatic variants (LM2-4/luc+ and 164/8-1B/luc+ in SCID, NOD-SCID
      and NOD-SCID-IL-2Rgamma(null) (NSG) mice following orthotopic implantation and
      primary tumour resection. The variants are known to be more aggressively
      metastatic in SCID mice, compared to the parental line which has limited
      spontaneous metastatic competence in these mice. When 2*106 cells were injected
      into the mammary fat pad, the growth of the resultant primary tumours was
      identical for the various cell lines in the three strains of mice. However,
      metastatic spread of all three cell lines, including the MDA-MB-231 parental cell
      line, was strikingly more aggressive in the highly immunocompromised NSG mice
      compared to both NOD-SCID and SCID mice, resulting in extensive multi-organ
      metastases and a significant reduction in overall survival. While these studies
      were facilitated by monitoring post-surgical spontaneous metastases using whole
      body bioluminescence imaging, we observed that the luciferase-tagged parental
      line showed altered growth and diminished metastatic properties compared to its
      untagged counterpart. Our results are the first to show that host immunity can
      have a profound impact on the spread of spontaneous visceral metastases and
      survival following resection of a primary tumour in circumstances where the
      growth of primary tumours is not similarly affected; as such they highlight the
      importance of immunity in the metastatic process, and by extension, suggest
      certain therapeutic strategies that may have a significant impact on reducing
      metastasis.

PMID- 23967179
TI  - Adiponectin protein exists in aortic endothelial cells.
AB  - AIMS: Inflammation is closely associated with the development of atherosclerosis
      and metabolic syndrome. Adiponectin, an adipose-derived secretory protein,
      possesses an anti-atherosclerotic property. The present study was undertaken to
      elucidate the presence and significance of adiponectin in vasculature. METHODS
      AND RESULTS: Immunofluorescence staining was performed in aorta of wild-type (WT)
      mice and demonstrated that adiponectin was co-stained with CD31. Thoracic aorta
      was cut through and then aortic intima was carefully shaved from aorta. Western
      blotting showed the existence of adiponectin protein in aortic intima, while
      there was no adiponectin mRNA expression. Adiponectin knockout (Adipo-KO) and WT
      mice were administered with a low-dose and short-term lipopolysaccharide (LPS) (1
      mg/kg of LPS for 4 hours). The endothelium vascular adhesion molecule-1 (VCAM-1)
      and intercellular adhesion molecule-1 (ICAM-1) were highly increased in Adipo-KO
      mice compared to WT mice after LPS administration. CONCLUSIONS: Adiponectin
      protein exists in aortic endothelium under steady state and may protect
      vasculature from the initiation of atherosclerosis.

PMID- 23967180
TI  - An evaluation of the left-brain vs. right-brain hypothesis with resting state
      functional connectivity magnetic resonance imaging.
AB  - Lateralized brain regions subserve functions such as language and visuospatial
      processing. It has been conjectured that individuals may be left-brain dominant
      or right-brain dominant based on personality and cognitive style, but
      neuroimaging data has not provided clear evidence whether such phenotypic
      differences in the strength of left-dominant or right-dominant networks exist. We
      evaluated whether strongly lateralized connections covaried within the same
      individuals. Data were analyzed from publicly available resting state scans for
      1011 individuals between the ages of 7 and 29. For each subject, functional
      lateralization was measured for each pair of 7266 regions covering the gray
      matter at 5-mm resolution as a difference in correlation before and after
      inverting images across the midsagittal plane. The difference in gray matter
      density between homotopic coordinates was used as a regressor to reduce the
      effect of structural asymmetries on functional lateralization. Nine left- and 11
      right-lateralized hubs were identified as peaks in the degree map from the graph
      of significantly lateralized connections. The left-lateralized hubs included
      regions from the default mode network (medial prefrontal cortex, posterior
      cingulate cortex, and temporoparietal junction) and language regions (e.g., Broca
      Area and Wernicke Area), whereas the right-lateralized hubs included regions from
      the attention control network (e.g., lateral intraparietal sulcus, anterior
      insula, area MT, and frontal eye fields). Left- and right-lateralized hubs formed
      two separable networks of mutually lateralized regions. Connections involving
      only left- or only right-lateralized hubs showed positive correlation across
      subjects, but only for connections sharing a node. Lateralization of brain
      connections appears to be a local rather than global property of brain networks,
      and our data are not consistent with a whole-brain phenotype of greater "left
      brained" or greater "right-brained" network strength across individuals. Small
      increases in lateralization with age were seen, but no differences in gender were
      observed. 

PMID- 23967181
TI  - Echocardiographic parameters in patients with pulmonary arterial hypertension:
      correlations with right ventricular ejection fraction derived from cardiac
      magnetic resonance and hemodynamics.
AB  - BACKGROUND: Echocardiography is the most convenient method used to evaluate right
      ventricular function, and several echocardiographic parameters were studied in
      previous studies. But the value of these parameters to assess the right
      ventricular function in patients with pulmonary arterial hypertension (PAH) has
      not been well defined. METHODS: Patients with PAH were observed prospectively.
      Right heart catheterization, echocardiography and cardiac magnetic resonance
      (CMR) were performed within 1 week interval. The correlations between
      echocardiographic parameters and right ventricular ejection fraction (RVEF)
      derived from CMR as well as hemodynamics were analyzed. RESULTS: Thirty patients
      were enrolled including 24 with idiopathic PAH, 5 with PAH associated with
      connective tissue diseases and 1 with hereditary PAH. All echocardiographic
      parameters except right ventricular myocardial performance index (RVMPI)
      correlated significantly with RVEF (tricuspid annual plane systolic excursion
      [TAPSE], r = 0.440, P = 0.015; tricuspid annular systolic excursion velocity
      [S'], r = 0.444, P = 0.016; isovolumic acceleration [IVA], r = 0.600, P = 0.001;
      right ventricular fraction area change [RVFAC], r = 0.416, P = 0.022; ratio of
      right ventricular transverse diameter to left ventricular transverse diameter
      [RVETD/LVETD], r = -0.649, P<0.001; RVMPI, r = -0.027, P = 0.888). After adjusted
      for mean right atrial pressure, mean pulmonary arterial pressure and pulmonary
      vascular resistance (PVR), only IVA and RVETD/LVETD could independently predict
      RVEF. Four echocardiographic parameters displayed significant correlations with
      PVR (TAPSE, r = -0.615, P<0.001; S', r = -0.557, P = 0.002; RVFAC, r = -0.454, P
      = 0.012; RVETD/LVETD, r = 0.543, P = 0.002). CONCLUSIONS: The echocardiographic
      parameters IVA and RVETD/LVETD can reflect RVEF independently regardless of
      hemodynamics in patients with PAH. In addition, TAPSE, S', RVFAC and RVETD/LVETD
      can also reflect PVR in PAH patients.

PMID- 23967182
TI  - A yeast-based chemical screen identifies a PDE inhibitor that elevates
      steroidogenesis in mouse Leydig cells via PDE8 and PDE4 inhibition.
AB  - A cell-based high-throughput screen (HTS) was developed to detect
      phosphodiesterase 8 (PDE8) and PDE4/8 combination inhibitors. By replacing the
      Schizosaccharomyces pombe PDE gene with the murine PDE8A1 gene in strains lacking
      adenylyl cyclase, we generated strains whose protein kinase A (PKA)-stimulated
      growth in 5-fluoro orotic acid (5FOA) medium reflects PDE8 activity. From our
      previously-identified PDE4 and PDE7 inhibitors, we identified a PDE4/8 inhibitor
      that allowed us to optimize screening conditions. Of 222,711 compounds screened,
      ~0.2% displayed composite Z scores of >20. Additional yeast-based assays using
      the most effective 367 compounds identified 30 candidates for further
      characterization. Among these, compound BC8-15 displayed the lowest IC50 value
      for both PDE4 and PDE8 inhibition in in vitro enzyme assays. This compound also
      displays significant activity against PDE10A and PDE11A. BC8-15 elevates
      steroidogenesis in mouse Leydig cells as a single pharmacological agent. Assays
      using BC8-15 and two structural derivatives support a model in which PDE8 is a
      primary regulator of testosterone production by Leydig cells, with an additional
      role for PDE4 in this process. BC8-15, BC8-15A, and BC8-15C, which are
      commercially available compounds, display distinct patterns of activity against
      PDE4, PDE8, PDE10A, and PDE11A, representing a chemical toolkit that could be
      used to examine the biological roles of these enzymes in cell culture systems.

PMID- 23967183
TI  - Serum MMP-8: a novel indicator of left ventricular remodeling and cardiac outcome
      in patients after acute myocardial infarction.
AB  - OBJECTIVE: Left ventricular (LV) remodeling following myocardial infarction (MI)
      is characterized by progressive alterations of structure and function, named LV
      remodeling. Although several risk factors such as infarct size have been
      identified, LV remodeling remains difficult to predict in clinical practice.
      Changes within the extracellular matrix, involving matrix metalloproteinases
      (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), are an integral part
      of left ventricular (LV) remodeling after myocardial infarction (MI). We
      investigated the temporal profile of circulating MMPs and TIMPs and their
      relations with LV remodeling at 1 year and clinical outcome at 3 years in post-MI
      patients. METHODS: This prospective multicentre study included 246 patients with
      a first anterior MI. Serial echocardiographic studies were performed at hospital
      discharge, 3 months, and 1 year after MI, and analysed at a core laboratory. LV
      remodeling was defined as the percent change in LV end-diastolic volume (EDV)
      from baseline to 1 year. Serum samples were obtained at hospital discharge, 1, 3,
      and 12 months. Multiplex technology was used for analysis of MMP-1, -2, -3, -8, 
      9, -13, and TIMP-1, -2, -3, -4 serum levels. RESULTS: Baseline levels of MMP-8
      and MMP-9 were positively associated with changes in LVEDV (P = 0.01 and 0.02,
      respectively). When adjusted for major baseline characteristics, MMP-8 levels
      remained an independent predictor LV remodeling (P = 0.025). By univariate
      analysis, there were positive relations between cardiovascular death or
      hospitalization for heart failure during the 3-year follow-up and the baseline
      levels of MMP-2 (P = 0.03), MMP-8 (P = 0.002), and MMP-9 (P = 0.03). By
      multivariate analysis, MMP-8 was the only MMP remaining significantly associated
      with clinical outcome (P = 0.02). CONCLUSION: Baseline serum MMP-8 is a
      significant predictor of LV remodeling and cardiovascular outcome after MI and
      may help to improve risk stratification.

PMID- 23967184
TI  - Niacin increases adiponectin and decreases adipose tissue inflammation in high
      fat diet-fed mice.
AB  - AIMS: To determine the effects of niacin on adiponectin and markers of adipose
      tissue inflammation in a mouse model of obesity. MATERIALS AND METHODS: Male
      C57BL/6 mice were placed on a control or high-fat diet (HFD) and were maintained
      on such diets for the duration of the study. After 6 weeks on the control or high
      fat diets, vehicle or niacin treatments were initiated and maintained for 5
      weeks. Identical studies were conducted concurrently in HCA2 (-/-) (niacin
      receptor(-/-)) mice. RESULTS: Niacin increased serum concentrations of the anti
      inflammatory adipokine, adiponectin by 21% in HFD-fed wild-type mice, but had no
      effect on lean wild-type or lean or HFD-fed HCA2 (-/-) mice. Niacin increased
      adiponectin gene and protein expression in the HFD-fed wild-type mice only. The
      increases in adiponectin serum concentrations, gene and protein expression
      occurred independently of changes in expression of PPARgamma C/EBPalpha or SREBP
      1c (key transcription factors known to positively regulate adiponectin gene
      transcription) in the adipose tissue. Further, niacin had no effect on adipose
      tissue expression of ERp44, Ero1-Lalpha, or DsbA-L (key ER chaperones involved in
      adiponectin production and secretion). However, niacin treatment attenuated HFD
      induced increases in adipose tissue gene expression of MCP-1 and IL-1beta in the
      wild-type HFD-fed mice. Niacin also reduced the expression of the pro
      inflammatory M1 macrophage marker CD11c in HFD-fed wild-type mice. CONCLUSIONS:
      Niacin treatment attenuates obesity-induced adipose tissue inflammation through
      increased adiponectin and anti-inflammatory cytokine expression and reduced pro
      inflammatory cytokine expression in a niacin receptor-dependent manner.

PMID- 23967185
TI  - Comparison between colony morphology and molecular phylogeny in the Caribbean
      scleractinian coral genus Madracis.
AB  - A major challenge in coral biology is to find the most adequate and
      phylogenetically informative characters that allow for distinction of closely
      related coral species. Therefore, data on corallite morphology and genetic data
      are often combined to increase phylogenetic resolution. In this study, we address
      the question to which degree genetic data and quantitative information on overall
      coral colony morphologies identify similar groupings within closely related
      morphospecies of the Caribbean coral genus Madracis. Such comparison of
      phylogenies based on colony morphology and genetic data will also provide insight
      into the degree to which genotype and phenotype overlap. We have measured
      morphological features of three closely related Caribbean coral species of the
      genus Madracis (M. formosa, M. decactis and M. carmabi). Morphological
      differences were then compared with phylogenies of the same species based on two
      nuclear DNA markers, i.e. ATPSalpha and SRP54. Our analysis showed that
      phylogenetic trees based on (macroscopical) morphological properties and
      phylogenetic trees based on DNA markers ATPSalpha and SRP54 are partially similar
      indicating that morphological characteristics at the colony level provide another
      axis, in addition to commonly used features such as corallite morphology and
      ecological information, to delineate genetically different coral species. We
      discuss this new method that allows systematic quantitative comparison between
      morphological characteristics of entire colonies and genetic data. 

PMID- 23967186
TI  - Variability of sleep duration is related to subjective sleep quality and
      subjective well-being: an actigraphy study.
AB  - While there is a large body of evidence that poor subjective sleep quality is
      related to lower subjective well-being, studies on the relation of objective
      sleep measures and subjective well-being are fewer in number and less consistent
      in their findings. Using data of the Survey of Mid-Life in the United States
      (MIDUS), we investigated whether duration and quality of sleep, assessed by
      actigraphy, were related to subjective well-being and whether this relationship
      was mediated by subjective sleep quality. Three hundred and thirteen mainly white
      American individuals from the general population and 128 urban-dwelling African
      American individuals between 35 and 85 years of age were studied cross
      sectionally. Sleep duration, variability of sleep duration, sleep onset latency,
      and time awake after sleep onset were assessed by actigraphy over a period of 7
      days. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality
      Index, positive psychological well-being and symptoms of psychological distress
      were assessed with the Satisfaction with Life Scale and the Mood and Anxiety
      Symptom Questionnaire. In both white and African Americans high day-to-day
      variability in sleep duration was related to lower levels of subjective well
      being controlling age, gender, educational and marital status, and BMI. By
      contrast, sleep duration, sleep onset latency, and time awake after sleep onset
      were not related to subjective well-being controlling covariates and other sleep
      variables. Moreover, the relationship between variability in sleep duration and
      well-being was partially mediated by subjective sleep quality. The findings show
      that great day-to-day variability in sleep duration--more than average sleep
      duration--is related to poor subjective sleep quality and poor subjective well
      being.

PMID- 23967187
TI  - Involvement of yeast HSP90 isoforms in response to stress and cell death induced
      by acetic acid.
AB  - Acetic acid-induced apoptosis in yeast is accompanied by an impairment of the
      general protein synthesis machinery, yet paradoxically also by the up-regulation
      of the two isoforms of the heat shock protein 90 (HSP90) chaperone family, Hsc82p
      and Hsp82p. Herein, we show that impairment of cap-dependent translation
      initiation induced by acetic acid is caused by the phosphorylation and
      inactivation of eIF2alpha by Gcn2p kinase. A microarray analysis of polysome
      associated mRNAs engaged in translation in acetic acid challenged cells further
      revealed that HSP90 mRNAs are over-represented in this polysome fraction
      suggesting preferential translation of HSP90 upon acetic acid treatment. The
      relevance of HSP90 isoform translation during programmed cell death (PCD) was
      unveiled using genetic and pharmacological abrogation of HSP90, which suggests
      opposing roles for HSP90 isoforms in cell survival and death. Hsc82p appears to
      promote survival and its deletion leads to necrotic cell death, while Hsp82p is a
      pro-death molecule involved in acetic acid-induced apoptosis. Therefore, HSP90
      isoforms have distinct roles in the control of cell fate during PCD and their
      selective translation regulates cellular response to acetic acid stress. 

PMID- 23967188
TI  - Prevalence of and risk factors for asymptomatic inflammatory (NIH-IV) prostatitis
      in Chinese men.
AB  - BACKGROUND: While many investigators have studied symptomatic prostatitis, little
      research has been done with regard to asymptomatic (NIH-IV) prostatitis. PURPOSE:
      To describe the prevalence of and risk factors for NIH-IV prostatitis among a
      large male population. METHODS: The study population was comprised of 1,868 men
      at the second phase recruitment of a population-based cohort in China.
      Asymptomatic and symptomatic men were defined by the National Institutes of
      Health Chronic Prostatitis (CP) Symptom Index. Meanwhile, EPS specimens and their
      leukocyte count were collected. Lifestyle and demographic characteristics were
      obtained through a questionnaire. RESULTS: Prevalence of NIH-IV prostatitis was
      21.1% among 1,868 asymptomatic men aged 19-78 years and increased with age. After
      adjusteing for potential confounding variables (age, smoking habits, alcohol
      drinking habits, education, physical activity, hypertension, dyslipidemia,
      obesity and diabetes), age remained a significant factor for NIH-IV prostatitis
      (OR = 1.35; 95% CI = 1.06-1.71; P = 0.01) and the risk of NIH-IV prostatitis was
      significantly higher in smokers?15 pack/years than non-smokers (OR = 1.33; 95% CI
      = 1.01-1.75; P = 0.03). In addition, compared with non-drinkers, the OR of NIH-IV
      prostatitis in drinkers ?1 drinks/week was 1.35 (95% CI = 1.03, 1.77, p = 0.02)
      after adjusting for the other variables above. In addition, having less than a
      college education may be a risk factor for NIH-IV prostatitis, although a
      statistically significant difference did not exist in our data (OR = 1.22; 95% CI
      = 0.97-1.52; P = 0.08). CONCLUSIONS: Our findings suggest that NIH-IV prostatitis
      is prevalent in China. Age, smoking, drinking and lower education levels were
      associated with an increased risk of NIH-IV prostatitis. The prevalence of NIH-IV
      prostatitis should be taken into account when estimating the total prevalence of
      CP in future studies.

PMID- 23967189
TI  - Implementation and assessment of an intervention to debias adolescents against
      causal illusions.
AB  - Researchers have warned that causal illusions are at the root of many
      superstitious beliefs and fuel many people's faith in pseudoscience, thus
      generating significant suffering in modern society. Therefore, it is critical
      that we understand the mechanisms by which these illusions develop and persist. A
      vast amount of research in psychology has investigated these mechanisms, but
      little work has been done on the extent to which it is possible to debias
      individuals against causal illusions. We present an intervention in which a
      sample of adolescents was introduced to the concept of experimental control,
      focusing on the need to consider the base rate of the outcome variable in order
      to determine if a causal relationship exists. The effectiveness of the
      intervention was measured using a standard contingency learning task that
      involved fake medicines that typically produce causal illusions. Half of the
      participants performed the contingency learning task before participating in the
      educational intervention (the control group), and the other half performed the
      task after they had completed the intervention (the experimental group). The
      participants in the experimental group made more realistic causal judgments than
      did those in the control group, which served as a baseline. To the best of our
      knowledge, this is the first evidence-based educational intervention that could
      be easily implemented to reduce causal illusions and the many problems associated
      with them, such as superstitions and belief in pseudoscience. 

PMID- 23967190
TI  - MicroRNA-221 mediates the effects of PDGF-BB on migration, proliferation, and the
      epithelial-mesenchymal transition in pancreatic cancer cells.
AB  - The platelet-derived growth factor (PDGF) signaling pathway has been found to
      play important roles in the development and progression of human cancers by
      regulating the processes of cell proliferation, apoptosis, migration, invasion,
      metastasis, and the acquisition of the epithelial-mesenchymal transition (EMT)
      phenotype. Moreover, PDGF signaling has also been found to alter the expression
      profile of miRNAs, leading to the reversal of EMT phenotype. Although the role of
      miRNAs in cancer has been documented, there are very few studies documenting the
      cellular consequences of targeted re-expression of specific miRNAs. Therefore, we
      investigated whether the treatment of human pancreatic cancer cells with PDGF
      could alter the expression profile of miRNAs, and we also assessed the cellular
      consequences. Our study demonstrates that miR-221 is essential for the PDGF
      mediated EMT phenotype, migration, and growth of pancreatic cancer cells. Down
      regulation of TRPS1 by miR-221 is critical for PDGF-mediated acquisition of the
      EMT phenotype. Additionally, the PDGF-dependent increase in cell proliferation
      appears to be mediated by inhibition of a specific target of miR-221 and down
      regulation of p27Kip1. 

PMID- 23967192
TI  - Structure and genetic content of the megaplasmids of neurotoxigenic clostridium
      butyricum type E strains from Italy.
AB  - We determined the genetic maps of the megaplasmids of six neutoroxigenic
      Clostridium butyricum type E strains from Italy using molecular and
      bioinformatics techniques. The megaplasmids are circular, not linear as we had
      previously proposed. The differently-sized megaplasmids share a genetic region
      that includes structural, metabolic and regulatory genes. In addition, we found
      that a 168 kb genetic region is present only in the larger megaplasmids of two
      tested strains, whereas it is absent from the smaller megaplasmids of the four
      remaining strains. The genetic region unique to the larger megaplasmids contains,
      among other features, a locus for clustered regularly interspaced short
      palindromic repeats (CRISPR) and CRISPR associated (cas) genes, i.e. a bacterial
      adaptive immune system providing sequence-specific protection from invading
      genetic elements. Some CRISPR spacer sequences of the neurotoxigenic C. butyricum
      type E strains showed homology to prophage, phage and plasmid sequences from
      closely related clostridia species or from distant species, all sharing the
      intestinal habitat, suggesting that the CRISPR locus might be involved in the
      microorganism adaptation to the human or animal intestinal environment. Besides,
      we report here that each of four distinct CRISPR spacers partially matched DNA
      sequences of different prophages and phages, at identical nucleotide locations.
      This suggests that, at least in neurotoxigenic C. butyricum type E, the CRISPR
      locus is potentially able to recognize the same conserved DNA sequence of
      different invading genetic elements, besides targeting sequences unique to
      previously encountered invading DNA, as currently predicted for a CRISPR locus.
      Thus, the results of this study introduce the possibility that CRISPR loci can
      provide resistance to a wider range of invading DNA elements than previously
      appreciated. Whether it is more advantageous for the peculiar neurotoxigenic C.
      butyricum type E strains to maintain or to lose the CRISPR-cas system remains an
      open question. 

PMID- 23967191
TI  - A selective HDAC 1/2 inhibitor modulates chromatin and gene expression in brain
      and alters mouse behavior in two mood-related tests.
AB  - Psychiatric diseases, including schizophrenia, bipolar disorder and major
      depression, are projected to lead global disease burden within the next decade.
      Pharmacotherapy, the primary--albeit often ineffective--treatment method, has
      remained largely unchanged over the past 50 years, highlighting the need for
      novel target discovery and improved mechanism-based treatments. Here, we examined
      in wild type mice the impact of chronic, systemic treatment with Compound 60 (Cpd
      60), a slow-binding, benzamide-based inhibitor of the class I histone deacetylase
      (HDAC) family members, HDAC1 and HDAC2, in mood-related behavioral assays
      responsive to clinically effective drugs. Cpd-60 treatment for one week was
      associated with attenuated locomotor activity following acute amphetamine
      challenge. Further, treated mice demonstrated decreased immobility in the forced
      swim test. These changes are consistent with established effects of clinical mood
      stabilizers and antidepressants, respectively. Whole-genome expression profiling
      of specific brain regions (prefrontal cortex, nucleus accumbens, hippocampus)
      from mice treated with Cpd-60 identified gene expression changes, including a
      small subset of transcripts that significantly overlapped those previously
      reported in lithium-treated mice. HDAC inhibition in brain was confirmed by
      increased histone acetylation both globally and, using chromatin
      immunoprecipitation, at the promoter regions of upregulated transcripts, a
      finding consistent with in vivo engagement of HDAC targets. In contrast,
      treatment with suberoylanilide hydroxamic acid (SAHA), a non-selective fast
      binding, hydroxamic acid HDAC 1/2/3/6 inhibitor, was sufficient to increase
      histone acetylation in brain, but did not alter mood-related behaviors and had
      dissimilar transcriptional regulatory effects compared to Cpd-60. These results
      provide evidence that selective inhibition of HDAC1 and HDAC2 in brain may
      provide an epigenetic-based target for developing improved treatments for mood
      disorders and other brain disorders with altered chromatin-mediated
      neuroplasticity.

PMID- 23967193
TI  - A novel TetR family transcriptional regulator, SAV576, negatively controls
      avermectin biosynthesis in Streptomyces avermitilis.
AB  - Avermectins produced by Streptomyces avermitilis are potent anti-parasitic agents
      that are useful in animal health care, agriculture, and the treatment of human
      infections. In a search for novel regulators that affect avermectin biosynthesis,
      comparative transcriptome analysis was performed between wild-type strain
      ATCC31267 and avermectin overproducing strain 76-02-e, revealing some
      differentially expressed genes. SAV576, which is downregulated in 76-02-e and
      encodes a TetR family transcriptional regulator (TFR), was shown to inhibit
      avermectin production by indirectly affecting the expression of ave genes. SAV576
      directly repressed the transcription of its gene SAV576 and of adjacent genes
      SAV575 (encodes cytochrome P450/NADPH-ferrihemoprotein reductase) and SAV574. The
      SAV576-binding sites within the bidirectional SAV575-SAV576 promoter region were
      determined by DNase I footprinting assays. A consensus 15-bp palindromic sequence
      CCRTACRVYGTATGS was found in these binding sites and shown to be important for
      SAV576-binding activity. SAV575, an important target gene of SAV576, was shown to
      exert a positive effect on avermectin production. The study findings extend our
      limited knowledge of the complex regulation of avermectin biosynthesis and
      provide a basis for rational genetic manipulation of S. avermitilis to improve
      avermectin production through control of SAV576 and its target gene. 

PMID- 23967194
TI  - Expansion of multipotent stem cells from the adult human brain.
AB  - The discovery of stem cells in the adult human brain has revealed new possible
      scenarios for treatment of the sick or injured brain. Both clinical use of and
      preclinical research on human adult neural stem cells have, however, been
      seriously hampered by the fact that it has been impossible to passage these cells
      more than a very few times and with little expansion of cell numbers. Having
      explored a number of alternative culturing conditions we here present an
      efficient method for the establishment and propagation of human brain stem cells
      from whatever brain tissue samples we have tried. We describe virtually unlimited
      expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and
      Oct4 are expressed without artificial induction. For the first time multipotency
      of adult human brain-derived stem cells is demonstrated beyond tissue boundaries.
      We characterize these cells in detail in vitro including microarray and proteomic
      approaches. Whilst clarification of these cells' behavior is ongoing, results so
      far portend well for the future repair of tissues by transplantation of an adult
      patient's own-derived stem cells. 

PMID- 23967195
TI  - Drug content effects on the dispersion performance of adhesive mixtures for
      inhalation.
AB  - The drug content in adhesive mixtures for inhalation is known to influence their
      dispersion performance, but the direction and magnitude of this influence depends
      on other variables. In the past decades several mechanisms have been postulated
      to explain this finding and a number of possible interacting variables have been
      identified. Still, the role of drug content in the formulation of adhesive
      mixtures for inhalation, which includes its significance as an interacting
      variable to other parameters, is poorly understood. Therefore, the results from a
      series of drug detachment experiments are presented in which the effect of drug
      content and its dependence on flow rate, the mixing time and the type of drug is
      studied. Furthermore, it is investigated whether the effect depends on the range
      within which the drug content is changed. Quantitative and qualitative multiple
      order interactions are observed between these variables, which may be explained
      by a shifting balance between three different mechanisms. The results therefore
      demonstrate that accounting for (multiple order) interactions between variables
      has to be part of quality by design activities and the rational design of future
      experiments. 

PMID- 23967197
TI  - De novo sequencing and transcriptome analysis of Wolfiporia cocos to reveal genes
      related to biosynthesis of triterpenoids.
AB  - Wolfiporia cocos Ryvarden et Gilbertson is a saprophytic fungus in the
      Basidiomycetes. Its dried sclerotium is widely used as a traditional crude drug
      in East Asia. Especially in China, the dried sclerotium is regarded as the silver
      of the Chinese traditional drugs, not only for its white color, but also its
      medicinal value. Furthermore, triterpenoids from W. cocos are the main active
      compounds with antitumor and anti-inflammatory activity. Biosynthesis of the
      triterpenoids has rarely been researched. In this study, the de novo sequencing
      of the mycelia and sclerotia of W. cocos were carried out by Illumina HiSeq 2000.
      A total of 3,484,996,740 bp from 38,722,186 sequence reads of mycelia, and
      3,573,921,960 bp from 39,710,244 high quality sequence reads of sclerotium were
      obtained. These raw data were assembled into 60,354 contigs and 40,939
      singletons, and 56,938 contigs and 37,220 singletons for mycelia and sclerotia,
      respectively. The transcriptomic data clearly showed that terpenoid biosynthesis
      was only via the MVA pathwayin W. cocos. The production of total triterpenoids
      and pachymic acid was examined in the dry mycelia and sclerotia. The content of
      total triterpenoids was 5.36% and 1.43% in mycelia and sclerotia, respectively,
      and the content of pachymic acid was 0.458% and 0.174%. Some genes involved in
      the triterpenoid biosynthetic pathway were chosen to be verified by qRT-PCR. The
      unigenes encoding diphosphomevalonate decarboxylase (Unigene 20430), farnesyl
      diphosphate synthase (Unigene 14106 and 21656), hydroxymethylglutaryl-CoA
      reductase (NADPH) (Unigene 6395_All) and lanosterol synthase (Unigene28001_All)
      were upregulated in the mycelia stage. It is likely that expression of these
      genes influences the biosynthesis of triterpenoids in the mycelia stage. 

PMID- 23967196
TI  - Human mesenchymal stem cells suppress the stretch-induced inflammatory miR-155
      and cytokines in bronchial epithelial cells.
AB  - Current research in pulmonary pathology has focused on inflammatory reactions
      initiated by immunological responses to allergens and irritants. In addition to
      these biochemical stimuli, physical forces also play an important role in
      regulating the structure, function, and metabolism of the lung. Hyperstretch of
      lung tissues can contribute to the inflammatory responses in asthma, but the
      mechanisms of mechanically induced inflammation in the lung remain unclear. Our
      results demonstrate that excessive stretch increased the secretion of
      inflammatory cytokines by human bronchial epithelial cells (hBECs), including IL
      8. This increase of IL-8 secretion was due to an elevated microRNA-155 (miR-155)
      expression, which caused the suppression of Src homology 2 domain-containing
      inositol 5-phosphatase 1 (SHIP1) production and the subsequent activation of JNK
      signaling. In vivo studies in our asthmatic mouse model also showed such changes
      in miR-155, IL-8, and SHIP1 expressions that reflect inflammatory responses. Co
      culture with human mesenchymal stem cells (hMSCs) reversed the stretch-induced
      hBEC inflammatory responses as a result of IL-10 secretion by hMSCs to down
      regulate miR-155 expression in hBECs. In summary, we have demonstrated that
      mechanical stretch modulates the homeostasis of the hBEC secretome involving miR
      155 and that hMSCs can be used as a potential therapeutic approach to reverse
      bronchial epithelial inflammation in asthma. 

PMID- 23967198
TI  - The STK33-linked SNP rs4929949 is associated with obesity and BMI in two
      independent cohorts of Swedish and Greek children.
AB  - Recent genome wide association studies (GWAS) have identified a locus on
      chromosome 11p15.5, closely associated with serine/threonine kinase 33 (STK33),
      to be associated with body mass. STK33, a relatively understudied protein, has
      been linked to KRAS mutation-driven cancers and explored as a potential
      antineoplastic drug target. The strongest association with body mass observed at
      this loci in GWAS was rs4929949, a single nucleotide polymorphism located within
      intron 1 of the gene encoding STK33. The functional implications of rs4929949 or
      related variants have not been explored as of yet. We have genotyped rs4929949 in
      two cohorts, an obesity case-control cohort of 991 Swedish children, and a cross
      sectional cohort of 2308 Greek school children. We found that the minor allele of
      rs4929949 was associated with obesity in the cohort of Swedish children and
      adolescents (OR = 1.199 (95%CI: 1.002-1.434), p = 0.047), and with body mass in
      the cross-sectional cohort of Greek children (beta = 0.08147 (95% CI: 0.1345
      0.1618), p = 0.021). We observe the effects of rs4929949 on body mass to be
      detectable already at adolescence. Subsequent analysis did not detect any
      association of rs4929949 to phenotypic measurements describing body adiposity or
      to metabolic factors such as insulin levels, triglycerides and insulin resistance
      (HOMA). 

PMID- 23967199
TI  - Urinary lipocalin protein in a female rodent with correlation to phases in the
      estrous cycle: an experimental study accompanied by in silico analysis.
AB  - Male urinary lipocalin family proteins, practically odorant-binding proteins but
      also could be pheromones by themselves, in rodents act as a shuttle for
      chemosignal communication and facilitate delivery of the signals for access to
      congeners. However, presence of this protein in urine of female rodents has not
      yet been reported. Therefore, the present investigation was carried out to find
      if lipocalin family protein is present in the urine of female house rat and, if
      so, to find whether its expression differs between the phases in the estrous
      cycle. The rat urinary protein was separated in single dimensional gel
      electrophoresis. A 14.5 kDa lipocalin protein appeared in the urine prominently
      during the estrus and metestrus phases compared to proestrus and diestrus phases.
      The expression of this protein in the urine was very low in ovariectomized rats.
      MALDI-TOF/MS analysis affirmed the 14.5 kDa protein as a lipocalin family
      protein. Analysis adopting bio-informatics tools further proved the protein as a
      lipocalin family member. Thus, this study for the first time demonstrated the
      presence of a lipocalin family protein in the urine of a female rodent and it was
      highly expressed during estrus phase. This lipocalin protein in female rat urine
      may facilitate a chemosignal function independently of a pheromone or in
      association with a specific pheromone. 

PMID- 23967200
TI  - STAT3 regulates MMP3 in heme-induced endothelial cell apoptosis.
AB  - BACKGROUND: We have previously reported that free Heme generated during
      experimental cerebral malaria (ECM) in mice, is central to the pathogenesis of
      fatal ECM. Heme-induced up-regulation of STAT3 and CXCL10 promotes whereas up
      regulation of HO-1 prevents brain tissue damage in ECM. We have previously
      demonstrated that Heme is involved in the induction of apoptosis in vascular
      endothelial cells. In the present study, we further tested the hypothesis that
      Heme reduces blood-brain barrier integrity during ECM by induction of apoptosis
      of brain vascular endothelial cells through STAT3 and its target gene matrix
      metalloproteinase three (MMP3) signaling. METHODS: Genes associated with the
      JAK/STAT3 signaling pathway induced upon stimulation by Heme treatment, were
      assessed using real time RT(2) Profile PCR arrays. A human MMP3 promoter was
      cloned into a luciferase reporter plasmid, pMMP3, and its activity was examined
      following exposure to Heme treatment by a luciferase reporter gene assay. In
      order to determine whether activated nuclear protein STAT3 binds to the MMP3
      promoter and regulates MMP3 gene, we conducted a ChIP analysis using Heme-treated
      and untreated human brain microvascular endothelial cells (HBVEC), and determined
      mRNA and protein expression levels of MMP3 using qRT-PCR and Western blot.
      Apoptosis in HBVEC treated with Heme was evaluated by MTT and TUNEL assay.
      RESULTS: The results show that (1) Heme activates a variety of JAK/STAT3
      downstream pathways in HBVEC. STAT3 targeted genes such as MMP3 and C/EBPb
      (Apoptosis-related genes), are up regulated in HBVEC treated with Heme. (2) Heme
      induced HBVEC apoptosis via activation of STAT3 as well as its downstream
      signaling molecule MMP3 and upregulation of CXCL10 and HO-1 expressions. (3)
      Phosphorylated STAT3 binds to the MMP3 promoter in HBVEC cells, STAT3 transcribed
      MMP3 and induced MMP3 protein expression in HBVEC cells. CONCLUSIONS: Activated
      STAT3 binds to the MMP3 promoter region and regulates MMP3 in Heme-induced
      endothelial cell apoptosis.

PMID- 23967202
TI  - Targeted exon sequencing successfully discovers rare causative genes and
      clarifies the molecular epidemiology of Japanese deafness patients.
AB  - Target exon resequencing using Massively Parallel DNA Sequencing (MPS) is a new
      powerful strategy to discover causative genes in rare Mendelian disorders such as
      deafness. We attempted to identify genomic variations responsible for deafness by
      massive sequencing of the exons of 112 target candidate genes. By the analysis of
      216randomly selected Japanese deafness patients (120 early-onset and 96 late
      detected), who had already been evaluated for common genes/mutations by Invader
      assay and of which 48 had already been diagnosed, we efficiently identified
      causative mutations and/or mutation candidates in 57 genes. Approximately 86.6%
      (187/216) of the patients had at least one mutation. Of the 187 patients, in 69
      the etiology of the hearing loss was completely explained. To determine which
      genes have the greatest impact on deafness etiology, the number of mutations was
      counted, showing that those in GJB2 were exceptionally higher, followed by
      mutations in SLC26A4, USH2A, GPR98, MYO15A, COL4A5 and CDH23. The present data
      suggested that targeted exon sequencing of selected genes using the MPS
      technology followed by the appropriate filtering algorithm will be able to
      identify rare responsible genes including new candidate genes for individual
      patients with deafness, and improve molecular diagnosis. In addition, using a
      large number of patients, the present study clarified the molecular epidemiology
      of deafness in Japanese. GJB2 is the most prevalent causative gene, and the major
      (commonly found) gene mutations cause 30-40% of deafness while the remainder of
      hearing loss is the result of various rare genes/mutations that have been
      difficult to diagnose by the conventional one-by-one approach. In conclusion,
      target exon resequencing using MPS technology is a suitable method to discover
      common and rare causative genes for a highly heterogeneous monogenic disease like
      hearing loss. 

PMID- 23967201
TI  - Mechanisms of seizure propagation in 2-dimensional centre-surround recurrent
      networks.
AB  - Understanding how seizures spread throughout the brain is an important problem in
      the treatment of epilepsy, especially for implantable devices that aim to avert
      focal seizures before they spread to, and overwhelm, the rest of the brain. This
      paper presents an analysis of the speed of propagation in a computational model
      of seizure-like activity in a 2-dimensional recurrent network of integrate-and
      fire neurons containing both excitatory and inhibitory populations and having a
      difference of Gaussians connectivity structure, an approximation to that observed
      in cerebral cortex. In the same computational model network, alternative
      mechanisms are explored in order to simulate the range of seizure-like activity
      propagation speeds (0.1-100 mm/s) observed in two animal-slice-based models of
      epilepsy: (1) low extracellular [Formula: see text], which creates excess
      excitation and (2) introduction of gamma-aminobutyric acid (GABA) antagonists,
      which reduce inhibition. Moreover, two alternative connection topologies are
      considered: excitation broader than inhibition, and inhibition broader than
      excitation. It was found that the empirically observed range of propagation
      velocities can be obtained for both connection topologies. For the case of the
      GABA antagonist model simulation, consistent with other studies, it was found
      that there is an effective threshold in the degree of inhibition below which
      waves begin to propagate. For the case of the low extracellular [Formula: see
      text] model simulation, it was found that activity-dependent reductions in
      inhibition provide a potential explanation for the emergence of slowly
      propagating waves. This was simulated as a depression of inhibitory synapses, but
      it may also be achieved by other mechanisms. This work provides a localised
      network understanding of the propagation of seizures in 2-dimensional centre
      surround networks that can be tested empirically. 

PMID- 23967203
TI  - Patterns of ecosystem metabolism in the Tonle Sap Lake, Cambodia with links to
      capture fisheries.
AB  - The Tonle Sap Lake in Cambodia is a dynamic flood-pulsed ecosystem that annually
      increases its surface area from roughly 2,500 km(2) to over 12,500 km(2) driven
      by seasonal flooding from the Mekong River. This flooding is thought to structure
      many of the critical ecological processes, including aquatic primary and
      secondary productivity. The lake also has a large fishery that supports the
      livelihoods of nearly 2 million people. We used a state-space oxygen mass balance
      model and continuous dissolved oxygen measurements from four locations to provide
      the first estimates of gross primary productivity (GPP) and ecosystem respiration
      (ER) for the Tonle Sap. GPP averaged 4.1+/-2.3 g O2 m(-3) d(-1) with minimal
      differences among sites. There was a negative correlation between monthly GPP and
      lake level (r = 0.45) and positive correlation with turbidity (r = 0.65). ER
      averaged 24.9+/-20.0 g O2 m(-3) d(-1) but had greater than six-fold variation
      among sites and minimal seasonal change. Repeated hypoxia was observed at most
      sampling sites along with persistent net heterotrophy (GPP<ER), indicating
      significant bacterial metabolism of organic matter that is likely incorporated
      into the larger food web. Using our measurements of GPP, we calibrated a
      hydrodynamic-productivity model and predicted aquatic net primary production
      (aNPP) of 2.0+/-0.2 g C m(-2) d(-1) (2.4+/-0.2 million tonnes C y(-1)).
      Considering a range of plausible values for the total fisheries catch, we
      estimate that fisheries harvest is an equivalent of 7-69% of total aNPP, which is
      substantially larger than global average for marine and freshwater systems. This
      is likely due to relatively efficient carbon transfer through the food web and
      support of fish production from terrestrial NPP. These analyses are an important
      first-step in quantifying the resource pathways that support this important
      ecosystem. 

PMID- 23967204
TI  - Large-scale spatial distribution patterns of gastropod assemblages in rocky
      shores.
AB  - Gastropod assemblages from nearshore rocky habitats were studied over large
      spatial scales to (1) describe broad-scale patterns in assemblage composition,
      including patterns by feeding modes, (2) identify latitudinal pattern of
      biodiversity, i.e., richness and abundance of gastropods and/or regional
      hotspots, and (3) identify potential environmental and anthropogenic drivers of
      these assemblages. Gastropods were sampled from 45 sites distributed within 12
      Large Marine Ecosystem regions (LME) following the NaGISA (Natural Geography in
      Shore Areas) standard protocol (www.nagisa.coml.org). A total of 393 gastropod
      taxa from 87 families were collected. Eight of these families (9.2%) appeared in
      four or more different LMEs. Among these, the Littorinidae was the most widely
      distributed (8 LMEs) followed by the Trochidae and the Columbellidae (6 LMEs). In
      all regions, assemblages were dominated by few species, the most diverse and
      abundant of which were herbivores. No latitudinal gradients were evident in
      relation to species richness or densities among sampling sites. Highest diversity
      was found in the Mediterranean and in the Gulf of Alaska, while highest densities
      were found at different latitudes and represented by few species within one genus
      (e.g. Afrolittorina in the Agulhas Current, Littorina in the Scotian Shelf, and
      Lacuna in the Gulf of Alaska). No significant correlation was found between
      species composition and environmental variables (r<=0.355, p>0.05). Contributing
      variables to this low correlation included invasive species, inorganic pollution,
      SST anomalies, and chlorophyll-a anomalies. Despite data limitations in this
      study which restrict conclusions in a global context, this work represents the
      first effort to sample gastropod biodiversity on rocky shores using a
      standardized protocol across a wide scale. Our results will generate more work to
      build global databases allowing for large-scale diversity comparisons of rocky
      intertidal assemblages. 

PMID- 23967205
TI  - Metabolomics and proteomics annotate therapeutic properties of geniposide:
      targeting and regulating multiple perturbed pathways.
AB  - Geniposide is an important constituent of Gardenia jasminoides Ellis, a famous
      Chinese medicinal plant, and has displayed bright prospects in prevention and
      therapy of hepatic injury (HI). Unfortunately, the working mechanisms of this
      compound are difficult to determine and thus remain unknown. To determine the
      mechanisms that underlie this compound, we conducted a systematic analysis of the
      therapeutic effects of geniposide using biochemistry, metabolomics and
      proteomics. Geniposide significantly intensified the therapeutic efficacy as
      indicated by our modern biochemical analysis. Metabolomics results indicate 9
      ions in the positive mode as differentiating metabolites which were associated
      with perturbations in primary bile acid biosynthesis, butanoate metabolism,
      citrate cycle (TCA cycle), alanine, aspartate and glutamate metabolism. Of note,
      geniposide has potential pharmacological effect through regulating multiple
      perturbed pathways to normal state. In an attempt to address the benefits of
      geniposide based on the proteomics approaches, the protein-interacting networks
      were constructed to aid identifying the drug targets of geniposide. Six
      identified differential proteins appear to be involved in antioxidation and
      signal transduction, energy production, immunity, metabolism, chaperoning. These
      proteins were closely related in the protein-protein interaction network and the
      modulation of multiple vital physiological pathways. These data will help to
      understand the molecular therapeutic mechanisms of geniposide on hepatic damage
      rats. We also conclude that metabolomics and proteomics are powerful and
      versatile tools for both biomarker discovery and exploring the complex
      relationships between biological pathways and drug response, highlighting
      insights into drug discovery. 

PMID- 23967206
TI  - Using seabird habitat modeling to inform marine spatial planning in central
      California's National Marine Sanctuaries.
AB  - Understanding seabird habitat preferences is critical to future wildlife
      conservation and threat mitigation in California. The objective of this study was
      to investigate drivers of seabird habitat selection within the Gulf of the
      Farallones and Cordell Bank National Marine Sanctuaries to identify areas for
      targeted conservation planning. We used seabird abundance data collected by the
      Applied California Current Ecosystem Studies Program (ACCESS) from 2004-2011. We
      used zero-inflated negative binomial regression to model species abundance and
      distribution as a function of near surface ocean water properties, distances to
      geographic features and oceanographic climate indices to identify patterns in
      foraging habitat selection. We evaluated seasonal, inter-annual and species
      specific variability of at-sea distributions for the five most abundant seabirds
      nesting on the Farallon Islands: western gull (Larus occidentalis), common murre
      (Uria aalge), Cassin's auklet (Ptychorampus aleuticus), rhinoceros auklet
      (Cerorhinca monocerata) and Brandt's cormorant (Phalacrocorax penicillatus). The
      waters in the vicinity of Cordell Bank and the continental shelf east of the
      Farallon Islands emerged as persistent and highly selected foraging areas across
      all species. Further, we conducted a spatial prioritization exercise to optimize
      seabird conservation areas with and without considering impacts of current human
      activities. We explored three conservation scenarios where 10, 30 and 50 percent
      of highly selected, species-specific foraging areas would be conserved. We
      compared and contrasted results in relation to existing marine protected areas
      (MPAs) and the future alternative energy footprint identified by the California
      Ocean Uses Atlas. Our results show that the majority of highly selected seabird
      habitat lies outside of state MPAs where threats from shipping, oil spills, and
      offshore energy development remain. This analysis accentuates the need for
      innovative marine spatial planning efforts and provides a foundation on which to
      build more comprehensive zoning and management in California's National Marine
      Sanctuaries. 

PMID- 23967207
TI  - Predictors of raised viral load during antiretroviral therapy in patients with
      and without prior antiretroviral use: a cross-sectional study.
AB  - OBJECTIVES: In Lagos, Nigeria, Medecins Sans Frontieres (MSF) and the Ministry of
      Health (MoH) commenced free antiretroviral treatment (ART) in a hospital-based
      clinic. We performed a cross-sectional study to compare factors associated with
      raised viral load between patients with ("experienced") and without ("naive")
      prior antiretroviral (ARV) exposure at commencement of ART at the clinic. We also
      examined factors influencing ARV adherence in experienced patients prior to
      clinic entry. METHODS: We included adult patients receiving ART from MSF who
      answered a questionnaire about previous antiretroviral use. Multivariate logistic
      regression was used to estimate odds ratios (OR) for raised viral load (>=1000
      copies/mL). RESULTS: 1246 (96%) patients answered: 1075 (86%) reported no, and
      171 (14%) some, prior ARV exposure. ARV-naive patients were more immunosuppressed
      at baseline: 65% vs 37% (p<0.001) had CD4<200; 17% vs 9% (p = 0.013) were WHO
      stage 4. Proportionately more experienced than naive patients had raised viral
      loads (20% vs 9%, p<0.001) on ART in the MSF/MoH clinic. Raised viral load was
      associated with prior ARV experience (adjusted OR = 3.74, 95%CI 2.09-6.70,
      p<0.001) and complete interruption of current ART (adjusted OR = 3.71, 95%CI 2.06
      6.68, p<0.001). Higher CD4 at time of VL and a higher self-rated score of recent
      adherence were associated with lower OR of a raised viral load. Among experienced
      patients who missed pills before joining MSF/MoH, most common reasons were
      because ARVS were not affordable (58%) or available (33%), with raised viral load
      associated with being unsure how to take them (OR = 3.16, 95%CI 1.10-9.12, p =
      0.033). CONCLUSIONS: Patients previously exposed to ARVs had increased OR of
      raised viral load. The cost and availability of ARVs were common reasons for
      missing ARVs before joining the MSF/MoH clinic, and inadequate patient knowledge
      was associated with raised viral load.

PMID- 23967208
TI  - c-Myc regulates proliferation and Fgf10 expression in airway smooth muscle after
      airway epithelial injury in mouse.
AB  - During lung development, Fibroblast growth factor 10 (Fgf10), which is expressed
      in the distal mesenchyme and regulated by Wnt signaling, acts on the distal
      epithelial progenitors to maintain them and prevent them from differentiating
      into proximal (airway) epithelial cells. Fgf10-expressing cells in the distal
      mesenchyme are progenitors for parabronchial smooth muscle cells (PSMCs). After
      naphthalene, ozone or bleomycin-induced airway epithelial injury, surviving
      epithelial cells secrete Wnt7b which then activates the PSMC niche to induce
      Fgf10 expression. This Fgf10 secreted by the niche then acts on a subset of Clara
      stem cells to break quiescence, induce proliferation and initiate epithelial
      repair. Here we show that conditional deletion of the Wnt target gene c-Myc from
      the lung mesenchyme during development does not affect proper epithelial or
      mesenchymal differentiation. However, in the adult lung we show that after
      naphthalene-mediated airway epithelial injury c-Myc is important for the
      activation of the PSMC niche and as such induces proliferation and Fgf10
      expression in PSMCs. Our data indicate that conditional deletion of c-Myc from
      PSMCs inhibits airway epithelial repair, whereas c-Myc ablation from Clara cells
      has no effect on airway epithelial regeneration. These findings may have
      important implications for understanding the misregulation of lung repair in
      asthma and COPD. 

PMID- 23967209
TI  - Identifying and targeting mortality disparities: a framework for sub-saharan
      Africa using adult mortality data from South Africa.
AB  - BACKGROUND: Health inequities in developing countries are difficult to eradicate
      because of limited resources. The neglect of adult mortality in Sub-Saharan
      Africa (SSA) is a particular concern. Advances in data availability, software and
      analytic methods have created opportunities to address this challenge and tailor
      interventions to small areas. This study demonstrates how a generic framework can
      be applied to guide policy interventions to reduce adult mortality in high risk
      areas. The framework, therefore, incorporates the spatial clustering of adult
      mortality, estimates the impact of a range of determinants and quantifies the
      impact of their removal to ensure optimal returns on scarce resources. METHODS:
      Data from a national cross-sectional survey in 2007 were used to illustrate the
      use of the generic framework for SSA and elsewhere. Adult mortality proportions
      were analyzed at four administrative levels and spatial analyses were used to
      identify areas with significant excess mortality. An ecological approach was then
      used to assess the relationship between mortality "hotspots" and various
      determinants. Population attributable fractions were calculated to quantify the
      reduction in mortality as a result of targeted removal of high-impact
      determinants. RESULTS: Overall adult mortality rate was 145 per 10,000. Spatial
      disaggregation identified a highly non-random pattern and 67 significant high
      risk local municipalities were identified. The most prominent determinants of
      adult mortality included HIV antenatal sero-prevalence, low SES and lack of
      formal marital union status. The removal of the most attributable factors, based
      on local area prevalence, suggest that overall adult mortality could be
      potentially reduced by ~90 deaths per 10,000. CONCLUSIONS: The innovative use of
      secondary data and advanced epidemiological techniques can be combined in a
      generic framework to identify and map mortality to the lowest administration
      level. The identification of high risk mortality determinants allows health
      authorities to tailor interventions at local level. This approach can be
      replicated elsewhere.

PMID- 23967211
TI  - External quality assessment of reading and interpretation of malaria rapid
      diagnostic tests among 1849 end-users in the Democratic Republic of the Congo
      through Short Message Service (SMS).
AB  - BACKGROUND: Although malaria rapid diagnostic tests (RDT) are simple to perform,
      they remain subject to errors, mainly related to the post-analytical phase. We
      organized the first large scale SMS based external quality assessment (EQA) on
      correct reading and interpretation of photographs of a three-band malaria RDT
      among laboratory health workers in the Democratic Republic of the Congo (DR
      Congo). METHODS AND FINDINGS: High resolution EQA photographs of 10 RDT results
      together with a questionnaire were distributed to health facilities in 9 out of
      11 provinces in DR Congo. Each laboratory health worker answered the EQA by Short
      Message Service (SMS). Filled-in questionnaires from each health facility were
      sent back to Kinshasa. A total of 1849 laboratory health workers in 1014 health
      facilities participated. Most frequent errors in RDT reading were i) failure to
      recognize invalid (13.2-32.5% ) or negative test results (9.8-12.8%), (ii)
      overlooking faint test lines (4.1-31.2%) and (iii) incorrect identification of
      the malaria species (12.1-17.4%). No uniform strategy for diagnosis of malaria at
      the health facility was present. Stock outs of RDTs occurred frequently. Half of
      the health facilities had not received an RDT training. Only two thirds used the
      RDT recommended by the National Malaria Control Program. Performance of RDT
      reading was positively associated with training and the technical level of health
      facility. Facilities with RDT positivity rates >50% and located in Eastern DR
      Congo performed worse. CONCLUSIONS: Our study confirmed that errors in reading
      and interpretation of malaria RDTs are widespread and highlighted the problem of
      stock outs of RDTs. Adequate training of end-users in the application of malaria
      RDTs associated with regular EQAs is recommended.

PMID- 23967210
TI  - 17beta-estradiol enhances signalling mediated by VEGF-A-delta-like ligand 4
      notch1 axis in human endothelial cells.
AB  - Estrogens play a protective role in coronary artery disease. The mechanisms of
      action are still poorly understood, although a role for estrogens in stimulation
      of angiogenesis has been suggested. In several cell types, estrogens modulate the
      Notch pathway, which is involved in controlling angiogenesis downstream of
      vascular endothelial growth factor A (VEGF-A). The goal of our study was to
      establish whether estrogens modulate Notch activity in endothelial cells and the
      possible consequences on angiogenesis. Human umbilical vein endothelial cells
      (HUVECs) were treated with 17beta-estradiol (E2) and the effects on Notch
      signalling were evaluated. E2 increased Notch1 processing as indicated by i)
      decreased levels of Notch1 transmembrane subunit ii) increased amount of Notch1
      in nuclei iii) unaffected level of mRNA. Similarly, E2 increased the levels of
      the active form of Notch4 without altering Notch4 mRNA. Conversely, protein and
      mRNA levels of Notch2 were both reduced suggesting transcriptional repression of
      Notch2 by E2. Under conditions where Notch was activated by upregulation of Delta
      like ligand 4 (Dll4) following VEGF-A treatment, E2 caused a further increase of
      the active form of Notch1, of the number of cells with nuclear Notch1 and of Hey2
      mRNA. Estrogen receptor antagonist ICI 182.780 antagonized these effects
      suggesting that E2 modulation of Notch1 is mediated by estrogen receptors. E2
      treatment abolished the increase in endothelial cells sprouting caused by Notch
      inhibition in a tube formation assay on 3D Matrigel and in mouse aortic ring
      explants. In conclusion, E2 affects several Notch pathway components in HUVECs,
      leading to an activation of the VEGF-A-Dll4-Notch1 axis and to a modulation of
      vascular branching when Notch signalling is inhibited. These results contribute
      to our understanding of the molecular mechanisms of cardiovascular protection
      exerted by estrogens by uncovering a novel role of E2 in the Notch signalling
      mediated modulation of angiogenesis. 

PMID- 23967212
TI  - Timing of favorable conditions, competition and fertility interact to govern
      recruitment of invasive Chinese tallow tree in stressful environments.
AB  - The rate of new exotic recruitment following removal of adult invaders
      (reinvasion pressure) influences restoration outcomes and costs but is highly
      variable and poorly understood. We hypothesize that broad variation in average
      reinvasion pressure of Triadica sebifera (Chinese tallow tree, a major invader)
      arises from differences among habitats in spatiotemporal availability of realized
      recruitment windows. These windows are periods of variable duration long enough
      to permit establishment given local environmental conditions. We tested this
      hypothesis via a greenhouse mesocosm experiment that quantified how the duration
      of favorable moisture conditions prior to flood or drought stress (window
      duration), competition and nutrient availability influenced Triadica success in
      high stress environments. Window duration influenced pre-stress seedling
      abundance and size, growth during stress and final abundance; it interacted with
      other factors to affect final biomass and germination during stress. Stress type
      and competition impacted final size and biomass, plus germination, mortality and
      changes in size during stress. Final abundance also depended on competition and
      the interaction of window duration, stress type and competition. Fertilization
      interacted with competition and stress to influence biomass and changes in
      height, respectively, but did not affect Triadica abundance. Overall, longer
      window durations promoted Triadica establishment, competition and drought
      (relative to flood) suppressed establishment, and fertilization had weak effects.
      Interactions among factors frequently produced different effects in specific
      contexts. Results support our 'outgrow the stress' hypothesis and show that
      temporal availability of abiotic windows and factors that influence growth rates
      govern Triadica recruitment in stressful environments. These findings suggest
      that native seed addition can effectively suppress superior competitors in
      stressful environments. We also describe environmental scenarios where specific
      management methods may be more or less effective. Our results enable better niche
      based estimates of local reinvasion pressure, which can improve restoration
      efficacy and efficiency by informing site selection and optimal management. 

PMID- 23967213
TI  - The ING4 Binding with p53 and Induced p53 Acetylation were Attenuated by Human
      Papillomavirus 16 E6.
AB  - High risk subtype HPV16 early oncoprotein E6 contributes host cell
      immortalization and transformation through interacting with a number of cellular
      factors. ING4 is one member of the inhibitor of growth (ING) family of type II
      tumor suppressors and it has been shown to be involved in regulating p53
      function. However, the effect and mechanism of HPV16 E6 on ING4 function remain
      elusive. In this study, we report HPV16 E6 combines with ING4 in vivo and in
      vitro. The ING4 induced p53 acetylation and its combining with p53 were
      attenuated by HPV16 E6 independent of p53 degradation. The enhancing function of
      ING4 on p53 mediated apoptosis was diminished when HPV16 E6 existed. These
      findings reveal that ING4 may be a common target of oncogenic viruses for driving
      host cell carcinogenesis. 

PMID- 23967214
TI  - Incidental findings on brain MR imaging in older community-dwelling subjects are
      common but serious medical consequences are rare: a cohort study.
AB  - OBJECTIVES: Incidental findings in neuroimaging occur in 3% of volunteers. Most
      data come from young subjects. Data on their occurrence in older subjects and
      their medical, lifestyle and financial consequences are lacking. We determined
      the prevalence and medical consequences of incidental findings found in community
      dwelling older subjects on brain magnetic resonance imaging. DESIGN: Prospective
      cohort observational study. SETTING: Single centre study with input from
      secondary care. PARTICIPANTS: Lothian Birth Cohort 1936, a study of cognitive
      ageing. MAIN OUTCOME MEASURES: Incidental findings identified by two consultant
      neuroradiologists on structural brain magnetic resonance imaging at age 73 years;
      resulting medical referrals and interventions. PRIMARY AND SECONDARY OUTCOME
      MEASURES: PREVALENCE OF INCIDENTAL FINDINGS BY INDIVIDUAL CATEGORIES: neoplasms,
      cysts, vascular lesions, developmental, ear, nose or throat anomalies, by intra-
      and extracranial location; visual rating of white matter hyperintensities and
      brain atrophy. RESULTS: There were 281 incidental findings in 223 (32%) of 700
      subjects, including 14 intra- or extracranial neoplasms (2%), 15 intracranial
      vascular anomalies (2%), and 137 infarcts or haemorrhages (20%). Additionally,
      153 had moderate/severe deep white matter hyperintensities (22%) and 176 had
      cerebral atrophy at, or above, the upper limit of normal (25%) compared with a
      normative population template. The incidental findings were unrelated to white
      matter hyperintensities or atrophy; about a third of subjects had both incidental
      findings and moderate or severe WMH and a quarter had incidental findings and
      atrophy. The incidental findings resulted in one urgent and nine non-urgent
      referrals for further medical assessment, but ultimately in no new treatments.
      CONCLUSIONS: In community-dwelling older subjects, incidental findings, including
      white matter hyperintensities and atrophy, were common. However, many findings
      were not of medical importance and, in this age group, most did not result in
      further assessment and none in change of treatment.

PMID- 23967215
TI  - Natural haemozoin induces expression and release of human monocyte tissue
      inhibitor of metalloproteinase-1.
AB  - Recently matrix metalloproteinase-9 (MMP-9) and its endogenous inhibitor (tissue
      inhibitor of metalloproteinase-1, TIMP-1) have been implicated in complicated
      malaria. In vivo, mice with cerebral malaria (CM) display high levels of both MMP
      9 and TIMP-1, and in human patients TIMP-1 serum levels directly correlate with
      disease severity. In vitro, natural haemozoin (nHZ, malarial pigment) enhances
      monocyte MMP-9 expression and release. The present study analyses the effects of
      nHZ on TIMP-1 regulation in human adherent monocytes. nHZ induced TIMP-1 mRNA
      expression and protein release, and promoted TNF-alpha, IL-1beta, and MIP
      1alpha/CCL3 production. Blocking antibodies or recombinant cytokines abrogated or
      mimicked nHZ effects on TIMP-1, respectively. p38 MAPK and NF-kappaB inhibitors
      blocked all nHZ effects on TIMP-1 and pro-inflammatory molecules. Still, total
      gelatinolytic activity was enhanced by nHZ despite TIMP-1 induction.
      Collectively, these data indicate that nHZ induces inflammation-mediated
      expression and release of human monocyte TIMP-1 through p38 MAPK- and NF-kappaB
      dependent mechanisms. However, TIMP-1 induction is not sufficient to
      counterbalance nHZ-dependent MMP-9 enhancement. Future investigation on
      proteinase-independent functions of TIMP-1 (i.e. cell survival promotion and
      growth/differentiation inhibition) is needed to clarify the role of TIMP-1 in
      malaria pathogenesis. 

PMID- 23967216
TI  - Underestimating calorie content when healthy foods are present: an averaging
      effect or a reference-dependent anchoring effect?
AB  - OBJECTIVE: Previous studies have shown that estimations of the calorie content of
      an unhealthy main meal food tend to be lower when the food is shown alongside a
      healthy item (e.g. fruit or vegetables) than when shown alone. This effect has
      been called the negative calorie illusion and has been attributed to averaging
      the unhealthy (vice) and healthy (virtue) foods leading to increased perceived
      healthiness and reduced calorie estimates. The current study aimed to replicate
      and extend these findings to test the hypothesized mediating effect of ratings of
      healthiness of foods on calorie estimates. METHODS: In three online studies,
      participants were invited to make calorie estimates of combinations of foods.
      Healthiness ratings of the food were also assessed. RESULTS: The first two
      studies failed to replicate the negative calorie illusion. In a final study, the
      use of a reference food, closely following a procedure from a previously
      published study, did elicit a negative calorie illusion. No evidence was found
      for a mediating role of healthiness estimates. CONCLUSION: The negative calorie
      illusion appears to be a function of the contrast between a food being judged and
      a reference, supporting the hypothesis that the negative calorie illusion arises
      from the use of a reference-dependent anchoring and adjustment heuristic and not
      from an 'averaging' effect, as initially proposed. This finding is consistent
      with existing data on sequential calorie estimates, and highlights a significant
      impact of the order in which foods are viewed on how foods are evaluated.

PMID- 23967217
TI  - MicroRNA-196a is a putative diagnostic biomarker and therapeutic target for
      laryngeal cancer.
AB  - BACKGROUND: MicroRNA (miRNA) is an emerging subclass of small non-coding RNAs
      that regulates gene expression and has a pivotal role for many physiological
      processes including cancer development. Recent reports revealed the role of
      miRNAs as ideal biomarkers and therapeutic targets due to their tissue- or
      disease-specific nature. Head and neck cancer (HNC) is a major cause of cancer
      related mortality and morbidity, and laryngeal cancer has the highest incidence
      in it. However, the molecular mechanisms involved in laryngeal cancer development
      remain to be known and highly sensitive biomarkers and novel promising therapy is
      necessary. METHODOLOGY/PRINCIPAL FINDINGS: To explore laryngeal cancer-specific
      miRNAs, RNA from 5 laryngeal surgical specimens including cancer and non-cancer
      tissues were hybridized to microarray carrying 723 human miRNAs. The resultant
      differentially expressed miRNAs were further tested by using quantitative real
      time PCR (qRT-PCR) on 43 laryngeal tissue samples including cancers, noncancerous
      counterparts, benign diseases and precancerous dysplasias. Significant
      expressional differences between matched pairs were reproduced in miR-133b, miR
      455-5p, and miR-196a, among which miR-196a being the most promising cancer
      biomarker as validated by qRT-PCR analyses on additional 84 tissue samples. Deep
      sequencing analysis revealed both quantitative and qualitative deviation of miR
      196a isomiR expression in laryngeal cancer. In situ hybridization confirmed
      laryngeal cancer-specific expression of miR-196a in both cancer and cancer stroma
      cells. Finally, inhibition of miR-196a counteracted cancer cell proliferation in
      both laryngeal cancer-derived cells and mouse xenograft model.
      CONCLUSIONS/SIGNIFICANCE: Our study provided the possibilities that miR-196a
      might be very useful in diagnosing and treating laryngeal cancer.

PMID- 23967218
TI  - High bacterial diversity of biological soil crusts in water tracks over
      permafrost in the high arctic polar desert.
AB  - In this study we report the bacterial diversity of biological soil crusts
      (biocrusts) inhabiting polar desert soils at the northern land limit of the
      Arctic polar region (83 degrees  05 N). Employing pyrosequencing of bacterial 16S
      rRNA genes this study demonstrated that these biocrusts harbor diverse bacterial
      communities, often as diverse as temperate latitude communities. The effect of
      wetting pulses on the composition of communities was also determined by
      collecting samples from soils outside and inside of permafrost water tracks, hill
      slope flow paths that drain permafrost-affected soils. The intermittent flow
      regime in the water tracks was correlated with altered relative abundance of
      phylum level taxonomic bins in the bacterial communities, but the alterations
      varied between individual sampling sites. Bacteria related to the Cyanobacteria
      and Acidobacteria demonstrated shifts in relative abundance based on their
      location either inside or outside of the water tracks. Among cyanobacterial
      sequences, the proportion of sequences belonging to the family Oscillatoriales
      consistently increased in relative abundance in the samples from inside the water
      tracks compared to those outside. Acidobacteria showed responses to wetting
      pulses in the water tracks, increasing in abundance at one site and decreasing at
      the other two sites. Subdivision 4 acidobacterial sequences tended to follow the
      trends in the total Acidobacteria relative abundance, suggesting these organisms
      were largely responsible for the changes observed in the Acidobacteria. Taken
      together, these data suggest that the bacterial communities of these high
      latitude polar biocrusts are diverse but do not show a consensus response to
      intermittent flow in water tracks over high Arctic permafrost. 

PMID- 23967219
TI  - Phenotypic and functional heterogeneity of bovine blood monocytes.
AB  - Murine and human peripheral blood monocytes are heterogeneous in size,
      granularity, nuclear morphology, phenotype and function. Whether and how bovine
      blood monocytes follow this pattern was analyzed in this study. Flow
      cytometrically, classical monocytes (cM) CD14+CD16-, intermediate monocytes
      (intM) CD14+ CD16+ and nonclassical monocytes (ncM) CD14+ CD16+ were identified,
      with cM being the predominant subset (89%). cM showed a significant lower
      expression of CD172a, intM expressed the highest level of MHC class II molecules,
      and ncM were low positive for CD163. Compared to cM and intM, ncM showed a
      significantly reduced phagocytosis capacity, a significantly reduced generation
      of reactive oxygen species, and reduced mRNA expression of CXCL8, CXCL1 and IL
      1beta after LPS stimulation. Based on IL-1beta secretion after LPS/ATP
      stimulation, the inflammasome could be activated in cM and intM, but not in ncM.
      IFNgamma increased the expression of CD16 selectively on cM and induced a shift
      from cM into intM in vitro. In summary, bovine CD172a-positive mononuclear cells
      define three monocyte subsets with distinct phenotypic and functional
      differences. Bovine cM and intM share homologies with their human counterparts,
      whereas bovine ncM are not inflammatory monocytes.

PMID- 23967220
TI  - Peripheral effects of nesfatin-1 on glucose homeostasis.
AB  - AIMS/HYPOTHESIS: The actions of peripherally administered nesfatin-1 on glucose
      homeostasis remain controversial. The aim of this study was to characterize the
      mechanisms by which peripheral nesfatin-1 regulates glucose metabolism. METHODS:
      The effects of nesfatin-1 on glucose metabolism were examined in mice by
      continuous infusion of the peptide via osmotic pumps. Changes in AKT
      phosphorylation and Glut4 were investigated by Western blotting and
      immnuofluorescent staining. Primary myocytes, adipocytes and hepatocytes were
      isolated from male mice. RESULTS: Continuous peripheral infusion of nesfatin-1
      altered glucose tolerance and insulin sensitivity in mice fed either normal or
      high fat diet, while central administration of nesfatin-1 demonstrated no effect.
      Nesfatin-1 increases insulin secretion in vivo, and in vitro in cultured min6
      cells. In addition, nesfatin-1 up-regulates the phosphorylation of AKT in
      pancreas and min6 islet cells. In mice fed normal diet, peripheral nesfatin-1
      significantly increased insulin-stimulated phosphorylation of AKT in skeletal
      muscle, adipose tissue and liver; similar effects were observed in skeletal
      muscle and adipose tissue in mice fed high fat diet. At basal conditions and
      after insulin stimulation, peripheral nesfatin-1 markedly increased GLUT4
      membrane translocation in skeletal muscle and adipose tissue in mice fed either
      diet. In vitro studies showed that nesfatin-1 increased both basal and insulin
      stimulated levels of AKT phosphorylation in cells derived from skeletal muscle,
      adipose tissue and liver. CONCLUSIONS: Our studies demonstrate that nesfatin-1
      alters glucose metabolism by mechanisms which increase insulin secretion and
      insulin sensitivity via altering AKT phosphorylation and GLUT 4 membrane
      translocation in the skeletal muscle, adipose tissue and liver.

PMID- 23967221
TI  - Seasonal and geographic variation of southern blue whale subspecies in the Indian
      Ocean.
AB  - Understanding the seasonal movements and distribution patterns of migratory
      species over ocean basin scales is vital for appropriate conservation and
      management measures. However, assessing populations over remote regions is
      challenging, particularly if they are rare. Blue whales (Balaenoptera musculus
      spp) are an endangered species found in the Southern and Indian Oceans. Here two
      recognized subspecies of blue whales and, based on passive acoustic monitoring,
      four "acoustic populations" occur. Three of these are pygmy blue whale (B.m.
      brevicauda) populations while the fourth is the Antarctic blue whale (B.m.
      intermedia). Past whaling catches have dramatically reduced their numbers but
      recent acoustic recordings show that these oceans are still important habitat for
      blue whales. Presently little is known about the seasonal movements and degree of
      overlap of these four populations, particularly in the central Indian Ocean. We
      examined the geographic and seasonal occurrence of different blue whale acoustic
      populations using one year of passive acoustic recording from three sites located
      at different latitudes in the Indian Ocean. The vocalizations of the different
      blue whale subspecies and acoustic populations were recorded seasonally in
      different regions. For some call types and locations, there was spatial and
      temporal overlap, particularly between Antarctic and different pygmy blue whale
      acoustic populations. Except on the southernmost hydrophone, all three pygmy blue
      whale acoustic populations were found at different sites or during different
      seasons, which further suggests that these populations are generally
      geographically distinct. This unusual blue whale diversity in sub-Antarctic and
      sub-tropical waters indicates the importance of the area for blue whales in these
      former whaling grounds. 

PMID- 23967222
TI  - Implementation of a bundle of care to reduce surgical site infections in patients
      undergoing vascular surgery.
AB  - BACKGROUND: Surgical site infections (SSI's) are associated with severe
      morbidity, mortality and increased health care costs in vascular surgery.
      OBJECTIVE: To implement a bundle of care in vascular surgery and measure the
      effects on the overall and deep-SSI's rates. DESIGN: Prospective, quasi
      experimental, cohort study. METHODS: A prospective surveillance for SSI's after
      vascular surgery was performed in the Amphia hospital in Breda, from 2009 through
      2011. A bundle developed by the Dutch hospital patient safety program (DHPSP) was
      introduced in 2009. The elements of the bundle were (1) perioperative
      normothermia, (2) hair removal before surgery, (3) the use of perioperative
      antibiotic prophylaxis and (4) discipline in the operating room. Bundle
      compliance was measured every 3 months in a random sample of surgical procedures
      and this was used for feedback. RESULTS: Bundle compliance improved significantly
      from an average of 10% in 2009 to 60% in 2011. In total, 720 vascular procedures
      were performed during the study period and 75 (10.4%) SSI were observed. Deep SSI
      occurred in 25 (3.5%) patients. Patients with SSI's (28,5+/-29.3 vs 10.8+/-11.3,
      p<0.001) and deep-SSI's (48.3+/-39.4 vs 11.4+/-11.8, p<0.001) had a significantly
      longer length of hospital stay after surgery than patients without an infection.
      A significantly higher mortality was observed in patients who developed a deep
      SSI (Adjusted OR: 2.96, 95% confidence interval 1.32-6.63). Multivariate analysis
      showed a significant and independent decrease of the SSI-rate over time that
      paralleled the introduction of the bundle. The SSI-rate was 51% lower in 2011
      compared to 2009. CONCLUSION: The implementation of the bundle was associated
      with improved compliance over time and a 51% reduction of the SSI-rate in
      vascular procedures. The bundle did not require expensive or potentially harmful
      interventions and is therefore an important tool to improve patient safety and
      reduce SSI's in patients undergoing vascular surgery.

PMID- 23967223
TI  - High adult sex ratios and risky sexual behaviors: a systematic review.
AB  - BACKGROUND: Thirty-four countries worldwide have abnormally high sex ratios (>102
      men per 100 women), resulting in over 100 million missing women. Widespread sex
      selective abortion, neglect of young girls leading to premature mortality, and
      gendered migration have contributed to these persistent and increasing
      distortions. Abnormally high adult sex ratios in communities may drive sexually
      transmitted disease (STD) spread where women are missing and men cannot find
      stable partners. We systematically reviewed evidence on the association between
      high community sex ratios and individual sexual behaviors. METHODS AND FINDINGS:
      Seven databases (PubMed, Web of Science, Embase, Scopus, The Cochrane Database of
      Systematic Reviews, Sociological Abstracts, and PopLINE) were searched without
      restrictions on time or location. We followed PRISMA guidelines and evaluated
      quality according to STROBE criteria. 1093 citations were identified and six
      studies describing 57,054 individuals were included for review. All six studies
      showed an association between high community sex ratios and individual sexual
      risk behaviors. In high sex ratio communities, women were more likely to have
      multiple sex partners and men were more likely to delay first sexual intercourse
      and purchase sex. Only two studies included STD outcomes. CONCLUSIONS: High
      community sex ratios were associated with increased individual sexual risk
      behavior among both men and women. However, none of the studies examined
      unprotected sex or appropriately adjusted for gendered migration. Further studies
      are needed to understand the effect of community sex ratios on sexual health and
      to inform comprehensive STD control interventions.

PMID- 23967224
TI  - How hot are drosophila hotspots? examining recombination rate variation and
      associations with nucleotide diversity, divergence, and maternal age in
      Drosophila pseudoobscura.
AB  - Fine scale meiotic recombination maps have uncovered a large amount of variation
      in crossover rate across the genomes of many species, and such variation in
      mammalian and yeast genomes is concentrated to <5kb regions of highly elevated
      recombination rates (10-100x the background rate) called "hotspots." Drosophila
      exhibit substantial recombination rate heterogeneity across their genome, but
      evidence for these highly-localized hotspots is lacking. We assayed recombination
      across a 40Kb region of Drosophila pseudoobscura chromosome 2, with one 20kb
      interval assayed every 5Kb and the adjacent 20kb interval bisected into 10kb
      pieces. We found that recombination events across the 40kb stretch were
      relatively evenly distributed across each of the 5kb and 10kb intervals, rather
      than concentrated in a single 5kb region. This, in combination with other recent
      work, indicates that the recombination landscape of Drosophila may differ from
      the punctate recombination pattern observed in many mammals and yeast.
      Additionally, we found no correlation of average pairwise nucleotide diversity
      and divergence with recombination rate across the 20kb intervals, nor any effect
      of maternal age in weeks on recombination rate in our sample. 

PMID- 23967225
TI  - Why has the continuous decline in German suicide rates stopped in 2007?
AB  - BACKGROUND: Whereas German suicide rates had a clear decreasing tendency between
      1991 and 2006, they increased from 2007 to 2010. Deeper analyses of suicide data
      might help to understand better this change. The aim of this study was to analyze
      1) whether recent trends can be related to changes in specific suicide methods
      and diverge by gender and age; 2) whether the decrease of suicide rates before
      2007 as well as the increase from 2007 to 2010 are driven by the same suicide
      method. METHODS: Analyses were based on suicide data from the Federal Statistical
      Office of Germany. For 1998-2010, 136.583 suicide cases of men and women with
      known age and suicide method could be identified. These data were analyzed by
      joinpoint regression analysis, allowing identification of the best fitting point
      in time ("joinpoint") at which the suicide rate significantly changes in
      magnitude or direction. RESULTS: The national downward trend between 1998 and
      2007 was mainly due to corresponding changes in self-poisoning by other means
      than drugs (e.g., pesticides) (annual percentage change (APC) <= -4.33), drowning
      (APC <= -2.73), hanging (APC <= -2.69) and suicides by firearms (APC <= -1.46) in
      both genders. Regarding the overall increase of age-adjusted suicide rates in
      Germany 2007-2010, mainly the increase of self-poisoning (e.g., by drugs) and
      "being overrun" (APC >= 1.50) contributed to this trend. LIMITATIONS: The true
      suicide rates might have been underestimated because of errors in the official
      death certificates. CONCLUSIONS: Increase in suicide rates in Germany since 2007
      went along with corresponding changes for "being overrun" and "self-poisoning".
      Copycat suicides following the railway suicide of the goalkeeper Robert Enke
      partly contributed to the results. Thus, prevention of Werther effects and
      limitation of the availability of high pack sizes for drugs are of special
      relevance for the reversal of this trend.

PMID- 23967226
TI  - HPV16 oncoproteins promote cervical cancer invasiveness by upregulating specific
      matrix metalloproteinases.
AB  - Production of matrix metalloproteinases (MMPs) for degradation of extracellular
      matrix is a vital step in cancer metastasis. We investigated the effects of HPV16
      oncoproteins (16E6, 16E6*I and 16E7), either individually or combined, on the
      transcription of 7 MMPs implicated in cervical cancer invasiveness. The levels of
      7 MMPs reported to be increased in cervical cancer were determined in C33A stably
      expressing different HPV16 oncoproteins using quantitative RT-PCR and compared
      with invasion ability of cell lines using in vitro invasion and wound healing
      assays. Overexpression of MMP-2 and MT1-MMP was detected in HPV16E6E7 expressing
      cells which correlated with increased cell invasion. Combination of HPV
      oncoproteins always showed greater effects than its individual form. Inhibition
      of cell invasion using a specific MMP-2 inhibitor, OA-Hy, and anti-MT1-MMP
      antibody confirmed that invasion in these cells was dependent on both MMP-2 and
      MT1-MMP expression. Depletion of HPV16E6E7 by shRNA-mediated knock-down
      experiments resulted in decreased MMP-2 and MT1-MMP expression levels as well as
      reduced invasion ability which strongly suggested specific effects of HPV
      oncoproteins on both MMPs and on cell invasion. Immunohistochemistry study in
      invasive cervical cancers confirmed the enhanced in vivo expression of these two
      MMPs in HPV16-infected cells. In addition, possible sites required by HPV16E6E7
      on the MMP-2 and MT1-MMP promoters were investigated and PEA3 (at -552/-540 for
      MMP-2, -303 for MT1-MMP) and Sp1 (at -91 for MMP-2, -102 for MT1-MMP) binding
      sites were shown to be essential for mediating their transactivation activity. In
      conclusion, our study demonstrated that HPV16E6 and E7 oncoproteins cooperate in
      promoting cervical cancer invasiveness by specifically upregulating MMP-2 and MT1
      MMP transcription in a similar manner. 

PMID- 23967227
TI  - Structural basis of alpha-catenin recognition by EspB from enterohaemorrhagic E.
      coli based on hybrid strategy using low-resolution structural and protein
      dissection.
AB  - Enterohaemorrhagic E. coli (EHEC) induces actin reorganization of host cells by
      injecting various effectors into host cytosol through type III secretion systems.
      EspB is the natively partially folded EHEC effector which binds to host alpha
      catenin to promote the actin bundling. However, its structural basis is poorly
      understood. Here, we characterize the overall structural properties of EspB based
      on low-resolution structural data in conjunction with protein dissection
      strategy. EspB showed a unique thermal response involving cold denaturation in
      the presence of denaturant according to far-UV circular dichroism (CD). Small
      angle X-ray scattering revealed the formation of a highly extended structure of
      EspB comparable to the ideal random coil. Various disorder predictions as well as
      CD spectra of EspB fragments identified the presence of alpha-helical structures
      around G41 to Q70. The fragment corresponding to this region indicated the
      thermal response similar to EspB. Moreover, this fragment showed a high affinity
      to C-terminal vinculin homology domain of alpha-catenin. The results clarified
      the importance of preformed alpha-helix of EspB for recognition of alpha-catenin.

PMID- 23967228
TI  - Fibroblast growth factor-4 enhances proliferation of mouse embryonic stem cells
      via activation of c-Jun signaling.
AB  - Fibroblast growth factor-4 (FGF4) is expressed in embryonic stages and in adult
      tissues, where it plays critical roles in modulating multiple cellular functions.
      However, the exact roles of FGF4 on proliferation and differentiation of
      embryonic stem cells (ESCs) are not completely understood. Exogenous addition of
      FGF4 stimulated proliferation of mouse ESCs (mESCs), as proven by the increases
      in DNA synthesis and cell cycle regulatory protein induction. These increases
      were almost completely inhibited by pre-treating cells with anti-FGF4 antibody.
      FGF4 also activated c-Jun N-terminal kinase (JNK) and extracellular-signal
      regulated kinase (ERK) signaling, but not p38 kinase. Blockage of JNK signaling
      by SP600125 or by transfection with its specific siRNA significantly inhibited
      FGF4-stimulated cell proliferation through the suppression of c-Jun induction and
      activator protein-1 (AP-1) activity. However, ERK or p38 kinase inhibitor did not
      affect FGF4-stimulated proliferation in mESCs. FGF4 suppressed osteogenic
      differentiation of mESCs by inhibiting expression of transcription factors
      involved in bone formation. Further, exogenous FGF4 addition stimulated
      proliferation of human periodontal ligament stem cells (hPDLSCs) and bone marrow
      mesenchymal stem cells (BMMSCs) via activation of ERK signaling. FGF4 also
      augmented mineralization of hPDLSCs, but not of BMMSCs. Collectively, it is
      suggested that FGF4 triggers proliferation of stem cells by activating MAPK
      mediated signaling, while it affects differently osteogenic differentiation
      according to the origins of stem cells. 

PMID- 23967229
TI  - Accurate and rapid identification of the Burkholderia pseudomallei near
      neighbour, Burkholderia ubonensis, using real-time PCR.
AB  - Burkholderia ubonensis is an environmental bacterium belonging to the
      Burkholderia cepacia complex (Bcc), a group of genetically related organisms that
      are associated with opportunistic but generally nonfatal infections in healthy
      individuals. In contrast, the near-neighbour species Burkholderia pseudomallei
      causes melioidosis, a disease that can be fatal in up to 95% of cases if left
      untreated. B. ubonensis is frequently misidentified as B. pseudomallei from soil
      samples using selective culturing on Ashdown's medium, reflecting both the shared
      environmental niche and morphological similarities of these species.
      Additionally, B. ubonensis shows potential as an important biocontrol agent in B.
      pseudomallei-endemic regions as certain strains possess antagonistic properties
      towards B. pseudomallei. Current methods for characterising B. ubonensis are
      laborious, time-consuming and costly, and as such this bacterium remains poorly
      studied. The aim of our study was to develop a rapid and inexpensive real-time
      PCR-based assay specific for B. ubonensis. We demonstrate that a novel B.
      ubonensis-specific assay, Bu550, accurately differentiates B. ubonensis from B.
      pseudomallei and other species that grow on selective Ashdown's agar. We
      anticipate that Bu550 will catalyse research on B. ubonensis by enabling rapid
      identification of this organism from Ashdown's-positive colonies that are not B.
      pseudomallei. 

PMID- 23967230
TI  - Detection of renal tissue and urinary tract proteins in the human urine after
      space flight.
AB  - The urine protein composition samples of ten Russian cosmonauts (male, aged of 35
      up to 51) performed long flight missions and varied from 169 up to 199 days on
      the International Space Station (ISS) were analyzed. As a control group, urine
      samples of six back-up cosmonauts were analyzed. We used proteomic techniques to
      obtain data and contemporary bioinformatics approaches to perform the analysis.
      From the total number of identified proteins (238) in our data set, 129 were
      associated with a known tissue origin. Preflight samples contained 92 tissue
      specific proteins, samples obtained on Day 1 after landing had 90 such proteins,
      while Day 7 samples offered 95 tissue-specific proteins. Analysis showed that
      consistently present proteins in urine (under physiological conditions and after
      space flight) are cubilin, epidermal growth factor, kallikrein-1, kininogen-1,
      megalin, osteopontin, vitamin K-dependent protein Z, uromodulin. Variably present
      proteins consists of: Na(+)/K(+) ATPase subunit gamma, beta-defensin-1,
      dipeptidyl peptidase 4, maltasa-glucoamilasa, cadherin-like protein, neutral
      endopeptidase and vascular cell adhesion protein 1. And only three renal proteins
      were related to the space flight factors. They were not found in the pre-flight
      samples and in the back-up cosmonaut urine, but were found in the urine samples
      after space flight: AFAM (afamin), AMPE (aminopeptidase A) and AQP2 (aquaporin
      2). This data related with physiological readaptation of water-salt balance. The
      proteomic analysis of urine samples in different phases of space missions with
      bioinformation approach to protein identification provides new data relative to
      biomechemical mechanism of kidney functioning after space flight. 

PMID- 23967231
TI  - Genomic deregulation of the E2F/Rb pathway leads to activation of the oncogene
      EZH2 in small cell lung cancer.
AB  - Small cell lung cancer (SCLC) is a highly aggressive lung neoplasm with extremely
      poor clinical outcomes and no approved targeted treatments. To elucidate the
      mechanisms responsible for driving the SCLC phenotype in hopes of revealing novel
      therapeutic targets, we studied copy number and methylation profiles of SCLC. We
      found disruption of the E2F/Rb pathway was a prominent feature deregulated in 96%
      of the SCLC samples investigated and was strongly associated with increased
      expression of EZH2, an oncogene and core member of the polycomb repressive
      complex 2 (PRC2). Through its catalytic role in the PRC2 complex, EZH2 normally
      functions to epigenetically silence genes during development, however, it
      aberrantly silences genes in human cancers. We provide evidence to support that
      EZH2 is functionally active in SCLC tumours, exerts pro-tumourigenic functions in
      vitro, and is associated with aberrant methylation profiles of PRC2 target genes
      indicative of a "stem-cell like" hypermethylator profile in SCLC tumours.
      Furthermore, lentiviral-mediated knockdown of EZH2 demonstrated a significant
      reduction in the growth of SCLC cell lines, suggesting EZH2 has a key role in
      driving SCLC biology. In conclusion, our data confirm the role of EZH2 as a
      critical oncogene in SCLC, and lend support to the prioritization of EZH2 as a
      potential therapeutic target in clinical disease. 

PMID- 23967232
TI  - Acute measles encephalitis in partially vaccinated adults.
AB  - BACKGROUND: The pathogenesis of acute measles encephalitis (AME) is poorly
      understood. Treatment with immune-modulators is based on theories that post
      infectious autoimmune responses cause demyelination. The clinical course and
      immunological parameters of AME were examined during an outbreak in Vietnam.
      METHODS AND FINDINGS: Fifteen measles IgM-positive patients with confusion or
      Glasgow Coma Scale (GCS) score below 13, and thirteen with uncomplicated measles
      were enrolled from 2008-2010. Standardized clinical exams were performed and
      blood collected for lymphocyte and measles- and auto-antibody analysis. The
      median age of AME patients was 21 years, similar to controls. Eleven reported
      receiving measles vaccination when aged one year. Confusion developed a median of
      4 days after rash. Six patients had GCS <8 and four required mechanical
      ventilation. CSF showed pleocytosis (64%) and proteinorrhachia (71%) but measles
      virus RNA was not detected. MRI revealed bilateral lesions in the cerebellum and
      brain stem in some patients. Most received dexamethasone +/- IVIG within 4 days
      of admission but symptoms persisted for >=3 weeks in five. The concentration of
      voltage gated calcium channel-complex-reactive antibodies was 900 pM in one
      patient, and declined to 609 pM ~ 3 months later. Measles-reactive IgG antibody
      avidity was high in AME patients born after vaccine coverage exceeded 50% (~ 25
      years earlier). AME patients had low CD4 (218/ul, p = 0.029) and CD8 (200/ul, p =
      0.012) T-cell counts compared to controls. CONCLUSION: Young adults presenting
      with AME in Vietnam reported a history of one prior measles immunization, and
      those aged <25 years had high measles-reactive IgG avidity indicative of prior
      vaccination. This suggests that one-dose measles immunization is not sufficient
      to prevent AME in young adults and reinforces the importance of maintaining high
      coverage with a two-dose measles immunization schedule. Treatment with
      corticosteroids and IVIG is common practice, and should be assessed in randomized
      clinical trials.

PMID- 23967233
TI  - Apoptotic and autophagic effects of Sesbania grandiflora flowers in human
      leukemic cells.
AB  - BACKGROUND: Identification of cytotoxic compounds that induce apoptosis has been
      the mainstay of anti-cancer therapeutics for several decades. In recent years,
      focus has shifted to inducing multiple modes of cell death coupled with reduced
      systemic toxicity. The plant Sesbania grandiflora is widely used in Indian
      traditional medicine for the treatment of a broad spectrum of diseases. This
      encouraged us to investigate into the anti-proliferative effect of a fraction
      (F2) isolated from S. grandiflora flowers in cancer cells and delineate the
      underlying involvement of apoptotic and autophagic pathways. PRINCIPAL FINDINGS:
      Using MTT based cell viability assay, we evaluated the cytotoxic potential of
      fraction F2. It was the most effective on U937 cells (IC50?18.6 ug/ml).
      Inhibition of growth involved enhancement of Annexin V positivity. This was
      associated with elevated reactive oxygen species generation, measured by flow
      cytometry and reduced oxygen consumption - both effects being abrogated by anti
      oxidant NAC. This caused stimulation of pro-apoptotic proteins and concomitant
      inhibition of anti-apoptotic protein expressions inducing mitochondrial
      depolarization, as measured by flow cytometry and release of cytochrome c.
      Interestingly, even with these molecular features of apoptosis, F2 was able to
      alter Atg protein levels and induce LC3 processing. This was accompanied by
      formation of autophagic vacuoles as revealed by fluorescence and transmission
      electron microscopy - confirming the occurrence of autophagy. Eventually, F2
      triggered caspase cascade - executioners of programmed cell death and AIF
      translocation to nuclei. This culminated in cleavage of the DNA repair enzyme,
      poly (ADP-ribose) polymerase that caused DNA damage as proved by staining with
      Hoechst 33258 leading to cell death. CONCLUSIONS: The findings suggest fraction
      F2 triggers pro-oxidant activity and mediates its cytotoxicity in leukemic cells
      via apoptosis and autophagy. Thus, it merits consideration and further
      investigation as a therapeutic option for the treatment of leukemia.

PMID- 23967234
TI  - Amniotic fluid stem cells inhibit the progression of bleomycin-induced pulmonary
      fibrosis via CCL2 modulation in bronchoalveolar lavage.
AB  - The potential for amniotic fluid stem cell (AFSC) treatment to inhibit the
      progression of fibrotic lung injury has not been described. We have previously
      demonstrated that AFSC can attenuate both acute and chronic-fibrotic kidney
      injury through modification of the cytokine environment. Fibrotic lung injury,
      such as in Idiopathic Pulmonary Fibrosis (IPF), is mediated through pro-fibrotic
      and pro-inflammatory cytokine activity. Thus, we hypothesized that AFSC treatment
      might inhibit the progression of bleomycin-induced pulmonary fibrosis through
      cytokine modulation. In particular, we aimed to investigate the effect of AFSC
      treatment on the modulation of the pro-fibrotic cytokine CCL2, which is increased
      in human IPF patients and is correlated with poor prognoses, advanced disease
      states and worse fibrotic outcomes. The impacts of intravenous murine AFSC given
      at acute (day 0) or chronic (day 14) intervention time-points after bleomycin
      injury were analyzed at either day 3 or day 28 post-injury. Murine AFSC treatment
      at either day 0 or day 14 post-bleomycin injury significantly inhibited collagen
      deposition and preserved pulmonary function. CCL2 expression increased in
      bleomycin-injured bronchoalveolar lavage (BAL), but significantly decreased
      following AFSC treatment at either day 0 or at day 14. AFSC were observed to
      localize within fibrotic lesions in the lung, showing preferential targeting of
      AFSC to the area of fibrosis. We also observed that MMP-2 was transiently
      increased in BAL following AFSC treatment. Increased MMP-2 activity was further
      associated with cleavage of CCL2, rendering it a putative antagonist for
      CCL2/CCR2 signaling, which we surmise is a potential mechanism for CCL2 reduction
      in BAL following AFSC treatment. Based on this data, we concluded that AFSC have
      the potential to inhibit the development or progression of fibrosis in a
      bleomycin injury model during both acute and chronic remodeling events. 

PMID- 23967235
TI  - Evaluation of injectable constructs for bone repair with a subperiosteal cranial
      model in the rat.
AB  - While testing regenerative medicine strategies, the use of animal models that
      match the research questions and that are related to clinical translation is
      crucial. During the initial stage of evaluating new strategies for bone repair,
      the main goal is to state whether the strategies efficiently induce the formation
      of new bone tissue at an orthotopic site. Here, we present a subperiosteal model
      in rat calvaria that allow the evaluation of a broad range of approaches
      including bone augmentation, replacement and regeneration. The model is a fast to
      perform, minimally invasive, and has clearly defined control groups. The
      procedure enables to evaluate the outcomes quantitatively using micro-computed
      tomography and qualitatively by histology and immunohistochemistry. We
      established this new model, using bone morphogenetic protein-2 as an
      osteoinductive factor and hyaluronic acid hydrogel as injectable biomaterial. We
      showed that this subperiosteal cranial model offers a minimally invasive and
      promising solution for a rapid initial evaluation of injectables for bone repair.
      We believe that this approach could be a powerful platform for orthopedic
      research and regenerative medicine. 

PMID- 23967236
TI  - Prenatal testosterone exposure worsen the reproductive performance of male rat at
      adulthood.
AB  - The reproductive system is extremely susceptible to environmental insults, for
      example exogenous steroids during gestational development and differentiation.
      Experimental induction of androgen excess during prenatal life in female animal
      models reprograms their reproductive physiology, however the fetal programming of
      the male reproductive system by androgen excess has not been well studied. We
      aimed to determine the effect of prenatal exposure of two different doses of
      testosterone on different gestational days, on the male reproductive system using
      a rat model. Sixteen pregnant rats were randomly divided into two experimental
      groups and two control groups. Experimental group I were subcutaneously injected
      with 3 mg free testosterone on gestational days 16-19 and its controls received
      solvent for that time; experimental group P were subcutaneously injected with 20
      mg free testosterone on day 20 of gestational period and its controls received
      solvent at the same time. The reproductive system morphology and function of 32
      male offspring of these study groups were compared at days 6-30-60 of age and
      after puberty. The anogenital distance of the male offspring of both experimental
      groups had no significant differences on the different days of measurement,
      compared with controls. In the offspring of experimental group I, the testes
      weight, number of Sertoli, Spermatocyte and Spermatid cells, sperm count and
      motility and the serum concentration of testosterone after puberty were
      significantly decreased; except for reduction of sperm motility (p< 0.01), the
      other effects were not observed in the offspring of experimental group II. In
      summary, our data show that prenatal exposure of male rat fetuses to excess
      testosterone disrupted reproductive function, an effect highly dependent on the
      time, duration and level of exposure. It seems that the reproductive system in
      individuals exposed to high levels of androgens during fetal life should be
      evaluated at puberty and likely to be treated. 

PMID- 23967237
TI  - Mouse leydig cells with different androgen production potential are resistant to
      estrogenic stimuli but responsive to bisphenol a which attenuates testosterone
      metabolism.
AB  - It is well known that estrogens and estrogen-like endocrine disruptors can
      suppress steroidogenic gene expression, attenuate androgen production and
      decrease differentiation of adult Leydig cell lineage. However, there is no
      information about the possible link between the potency of Leydig cells to
      produce androgens and their sensitivity to estrogenic stimuli. Thus, the present
      study explored the relationship between androgen production potential of Leydig
      cells and their responsiveness to estrogenic compounds. To investigate this
      relationship we selected mouse genotypes contrasting in sex hormone levels and
      differing in testosterone/estradiol (T/E2) ratio. We found that two mouse
      genotypes, CBA/Lac and C57BL/6j have the highest and the lowest serum T/E2 ratio
      associated with increased serum LH level in C57BL/6j compared to CBA/Lac.
      Analysis of steroidogenic gene expression demonstrated significant upregulation
      of Cyp19 gene expression but coordinated suppression of LHR, StAR, 3betaHSDI and
      Cyp17a1 in Leydig cells from C57BL/6j that was associated with attenuated
      androgen production in basal and hCG-stimulated conditions compared to CBA/Lac
      mice. These genotype-dependent differences in steroidogenesis were not linked to
      changes in the expression of estrogen receptors ERalpha and Gpr30, while ERbeta
      expression was attenuated in Leydig cells from C57BL/6j compared to CBA/Lac. No
      effects of estrogenic agonists on steroidogenesis in Leydig cells from both
      genotypes were found. In contrast, xenoestrogen bisphenol A significantly
      potentiated hCG-activated androgen production by Leydig cells from C57BL/6j and
      CBA/Lac mice by suppressing conversion of testosterone into corresponding
      metabolite 5alpha-androstane-3alpha,17beta-diol. All together our data indicate
      that developing mouse Leydig cells with different androgen production potential
      are resistant to estrogenic stimuli, while xenoestrogen BPA facilitates hCG
      induced steroidogenesis in mouse Leydig cells via attenuation of testosterone
      metabolism. This cellular event can cause premature maturation of Leydig cells
      that may create abnormal intratesticular paracrine milieu and disturb proper
      development of germ cells. 

PMID- 23967238
TI  - Functional testing of an inhalable nanoparticle based influenza vaccine using a
      human precision cut lung slice technique.
AB  - Annual outbreaks of influenza infections, caused by new influenza virus subtypes
      and high incidences of zoonosis, make seasonal influenza one of the most
      unpredictable and serious health threats worldwide. Currently available vaccines,
      though the main prevention strategy, can neither efficiently be adapted to new
      circulating virus subtypes nor provide high amounts to meet the global demand
      fast enough. New influenza vaccines quickly adapted to current virus strains are
      needed. In the present study we investigated the local toxicity and capacity of a
      new inhalable influenza vaccine to induce an antigen-specific recall response at
      the site of virus entry in human precision-cut lung slices (PCLS). This new
      vaccine combines recombinant H1N1 influenza hemagglutinin (HAC1), produced in
      tobacco plants, and a silica nanoparticle (NP)-based drug delivery system. We
      found no local cellular toxicity of the vaccine within applicable concentrations.
      However higher concentrations of NP (>=10(3) ug/ml) dose-dependently decreased
      viability of human PCLS. Furthermore NP, not the protein, provoked a dose
      dependent induction of TNF-alpha and IL-1beta, indicating adjuvant properties of
      silica. In contrast, we found an antigen-specific induction of the T cell
      proliferation and differentiation cytokine, IL-2, compared to baseline level
      (152+/-49 pg/mg vs. 22+/-5 pg/mg), which could not be seen for the NP alone.
      Additionally, treatment with 10 ug/ml HAC1 caused a 6-times higher secretion of
      IFN-gamma compared to baseline (602+/-307 pg/mg vs. 97+/-51 pg/mg). This antigen
      induced IFN-gamma secretion was further boosted by the adjuvant effect of silica
      NP for the formulated vaccine to a 12-fold increase (97+/-51 pg/mg vs. 1226+/-535
      pg/mg). Thus we were able to show that the plant-produced vaccine induced an
      adequate innate immune response and re-activated an established antigen-specific
      T cell response within a non-toxic range in human PCLS at the site of virus
      entry. 

PMID- 23967239
TI  - Molecular characterization of poxviruses associated with tattoo skin lesions in
      UK cetaceans.
AB  - There is increasing concern for the well-being of cetacean populations around the
      UK. Tattoo skin disease (characterised by irregular, grey, black or yellowish,
      stippled cutaneous lesions) caused by poxvirus infection is a potential health
      indicatora potential health indicator for cetaceans. Limited sequence data
      indicates that cetacean poxviruses (CPVs) belong to an unassigned genus of the
      Chordopoxvirinae. To obtain further insight into the phylogenetic relationships
      between CPV and other Chordopoxvirinae members we partially characterized viral
      DNA originating from tattoo lesions collected in Delphinidae and Phocoenidae
      stranded along the UK coastline in 1998-2008. We also evaluated the presence of
      CPV in skin lesions other than tattoos to examine specificity and sensitivity of
      visual diagnosis. After DNA extraction, regions of the DNA polymerase and DNA
      topoisomerase I genes were amplified by PCR, sequenced and compared with other
      isolates. The presence of CPV DNA was demonstrated in tattoos from one striped
      dolphin (Stenella coeruleoalba), eight harbour porpoises (Phocoena phocoena) and
      one short-beaked common dolphin (Delphinus delphis) and in one 'dubious tattoo'
      lesion detected in one other porpoise. Seventeen of the 18 PCR positive skin
      lesions had been visually identified as tattoos and one as a dubious tattoo. None
      of the other skin lesions were PCR positive. Thus, visual identification had a
      94.4% sensitivity and 100% specificity. The DNA polymerase PCR was most effective
      in detecting CPV DNA. Limited sequence phylogeny grouped the UK samples within
      the odontocete poxviruses (CPV group 1) and indicated that two different poxvirus
      lineages infect the Phocoenidae and the Delphinidae. The phylogenetic tree had
      three major branches: one with the UK Phocoenidae viruses, one with the
      Delphinidae isolates and one for the mysticete poxvirus (CPV group 2). This
      implies a radiation of poxviruses according to the host suborder and the families
      within these suborders. 

PMID- 23967240
TI  - Mesenchymal stromal (stem) cell therapy fails to improve outcomes in experimental
      severe influenza.
AB  - RATIONALE: Severe influenza remains a major public health threat and is
      responsible for thousands of deaths annually. Increasing antiviral resistance and
      limited effectiveness of current therapies highlight the need for new approaches
      to influenza treatment. Extensive pre-clinical data have shown that mesenchymal
      stromal (stem) cell (MSC) therapy can induce anti-inflammatory effects and
      enhance repair of the injured lung. We hypothesized that MSC therapy would
      improve survival, dampen lung inflammation and decrease acute lung injury (ALI)
      in a murine model of severe influenza. METHODS: C57Bl/6 mice were infected with
      influenza A/PuertoRico/8/34 (mouse-adapted H1N1) or influenza A/Mexico/4108/2009
      (swine-origin pandemic H1N1) and administered human or mouse MSCs via the tail
      vein, either pre- or post- infection. MSC efficacy was evaluated as both an
      independent and adjunctive treatment strategy in combination with the antiviral
      agent, oseltamivir. Weight loss and survival were monitored. Inflammatory cells,
      cytokine/chemokines (IFN-gamma, CXCL10, CCL2 and CCL5) and markers of ALI (total
      protein and IgM), were measured in bronchoalveolar lavage fluid and lung
      parenchyma. RESULTS: Administration of murine MSCs or human MSCs in a
      prophylactic or therapeutic regimen failed to improve survival, decrease
      pulmonary inflammation/inflammatory cell counts or prevent ALI in influenza virus
      infected mice. MSCs administered in combination with oseltamivir also failed to
      improve outcomes. CONCLUSIONS: Despite similarities in the clinical presentation
      and pathobiology of ALI and severe influenza, our findings suggest that MSC
      therapy may not be effective for prevention and/or treatment of acute severe
      influenza.

PMID- 23967241
TI  - Seroprevalence of antibodies to highly pathogenic avian influenza A (H5N1) virus
      among close contacts exposed to H5N1 cases, China, 2005-2008.
AB  - To assess the extent of highly pathogenic avian influenza (HPAI) A (H5N1) virus
      transmission, we conducted sero-epidemiologic studies among close contacts
      exposed to H5N1 cases in mainland China during 2005-2008. Blood specimens were
      collected from 87 household members and 332 social contacts of 23 H5N1 index
      cases for HPAI H5N1 serological testing by modified horse red-blood-cell
      hemagglutinin inhibition and microneutralization assays. All participants were
      interviewed with a standardized questionnaire to collect information about the
      use of personal protective equipment, illness symptoms, exposure to an H5N1 case
      during the infectious period, and poultry exposures. Two (2.3%) household
      contacts tested positive for HPAI H5N1 virus antibody, and all social contacts
      tested negative. Both seropositive cases had prolonged, unprotected, close
      contact with a different H5N1 index case, including days of bed-care or sleeping
      together during the index case's infectious period, and did not develop any
      illness. None of the 419 close contacts used appropriate personal protective
      equipment including 17% who reported providing bedside care or having physical
      contact with an H5N1 case for at least 12 hours. Our findings suggest that HPAI
      H5N1 viruses that circulated among poultry in mainland China from 2005-2008 were
      not easily transmitted to close contacts of H5N1 cases. 

PMID- 23967242
TI  - Epidermal growth factor receptor down-regulation triggers human myoblast
      differentiation.
AB  - Initiation of human myoblast differentiation requires a negative shift
      (hyperpolarization) of the resting potential of myoblasts that depends on the
      activation of Kir2.1 potassium channels. These channels are regulated by a
      tyrosine phosphorylation. Using human primary myoblast culture, we investigated a
      possible role of various receptor tyrosine kinases in the induction of the
      differentiation process. We found that Epidermal Growth Factor Receptor (EGFR) is
      a key regulator of myoblast differentiation. EGFR activity is down-regulated
      during early human myoblast differentiation, and this event is required for
      normal differentiation to take place. Furthermore, EGFR silencing in
      proliferation conditions was able to trigger the differentiation program. This
      occurs through an increase of Kir2.1 channel activity that, via a rise of store
      operated Ca(2+) entry, leads to the expression of myogenic transcription factors
      and muscle specific proteins (Myogenin, Myocyte Enhancer Factor 2 (MEF2), Myosin
      Heavy Chain (MyHC)). Finally, blocking myoblast cell cycle in proliferation
      conditions using a cdk4 inhibitor greatly decreased myoblast proliferation but
      was not able, on its own, to promote myoblast differentiation. Taken together,
      these results show that EGFR down-regulation is an early event that is required
      for the induction of myoblast differentiation. 

PMID- 23967243
TI  - The cultural evolution of human communication systems in different sized
      populations: usability trumps learnability.
AB  - This study examines the intergenerational transfer of human communication
      systems. It tests if human communication systems evolve to be easy to learn or
      easy to use (or both), and how population size affects learnability and
      usability. Using an experimental-semiotic task, we find that human communication
      systems evolve to be easier to use (production efficiency and reproduction
      fidelity), but harder to learn (identification accuracy) for a second generation
      of naive participants. Thus, usability trumps learnability. In addition, the
      communication systems that evolve in larger populations exhibit distinct
      advantages over those that evolve in smaller populations: the learnability loss
      (from the Initial signs) is more muted and the usability benefits are more
      pronounced. The usability benefits for human communication systems that evolve in
      a small and large population is explained through guided variation reducing sign
      complexity. The enhanced performance of the communication systems that evolve in
      larger populations is explained by the operation of a content bias acting on the
      larger pool of competing signs. The content bias selects for information
      efficient iconic signs that aid learnability and enhance usability. 

PMID- 23967244
TI  - TDP-43, an ALS linked protein, regulates fat deposition and glucose homeostasis.
AB  - The identification of proteins which determine fat and lean body mass composition
      is critical to better understanding and treating human obesity. TDP-43 is a well
      conserved RNA-binding protein known to regulate alternative splicing and recently
      implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). While TDP
      43 knockout mice show early embryonic lethality, post-natal conditional knockout
      mice show weight loss, fat depletion, and rapid death, suggesting an important
      role for TDP-43 in regulating energy metabolism. Here we report, that over
      expression of TDP-43 in transgenic mice can result in a phenotype characterized
      by increased fat deposition and adipocyte hypertrophy. In addition, TDP-43 over
      expression in skeletal muscle results in increased steady state levels of Tbc1d1,
      a RAB-GTPase activating protein involved in Glucose 4 transporter (Glut4)
      translocation. Skeletal muscle fibers isolated from TDP-43 transgenic mice show
      altered Glut4 translocation in response to insulin and impaired insulin mediated
      glucose uptake. These results indicate that levels of TDP-43 regulate body fat
      composition and glucose homeostasis in vivo. 

PMID- 23967245
TI  - Camkii-mediated phosphorylation regulates distributions of Syngap-alpha1 and 
      alpha2 at the postsynaptic density.
AB  - SynGAP, a protein abundant at the postsynaptic density (PSD) of glutamatergic
      neurons, is known to modulate synaptic strength by regulating the incorporation
      of AMPA receptors at the synapse. Two isoforms of SynGAP, alpha1 and alpha2,
      which differ in their C-termini, have opposing effects on synaptic strength. In
      the present study, antibodies specific for SynGAP-alpha1 and SynGAP-alpha2 are
      used to compare the distribution patterns of the two isoforms at the postsynaptic
      density (PSD) under basal and excitatory conditions. Western immunoblotting shows
      enrichment of both isoforms in PSD fractions isolated from adult rat brain.
      Immunogold electron microscopy of rat hippocampal neuronal cultures shows similar
      distribution of both isoforms at the PSD, with a high density of immunolabel
      within the PSD core under basal conditions. Application of NMDA promotes movement
      of SynGAP-alpha1 as well as SynGAP-alpha2 out of the PSD core. In isolated PSDs
      both isoforms of SynGAP can be phosphorylated upon activation of the endogenous
      CaMKII. Application of tatCN21, a cell-penetrating inhibitor of CaMKII, to
      hippocampal neuronal cultures blocks NMDA-induced redistribution of SynGAP-alpha1
      and SynGAP-alpha2. Thus CaMKII activation promotes the removal of two distinct C
      terminal SynGAP variants from the PSD. 

PMID- 23967246
TI  - Estimating the size of HIV key affected populations in Chongqing, China, using
      the network scale-up method.
AB  - OBJECTIVES: To estimate the average social network size in the general population
      and the size of HIV key affected populations (KAPs) in Chongqing municipality
      using the network scale-up method (NSUM). METHODS: A general population survey
      was conducted in 2011 through a multistage random sampling method. Participants
      aged between 18 and 60 years were recruited. The average social network size (c)
      was estimated and adjusted by known population method. The size of HIV KAP in
      Chongqing municipality was estimated using the adjusted c value with adjustment
      for the transmission effect using the scaled respect factor. RESULTS: 3,026
      inhabitants of Chongqing agreed to the survey, and 2,957 (97.7%) completed the
      questionnaire. The adjusted c value was 310. The estimated size of KAP was
      28,418(95% Confidence Interval (CI):26,636~30,201) for female sex workers (FSW),
      163,199(95%CI:156,490~169,908) for clients of FSW, 37,959(95%CI: 34,888~41,030)
      for drug users (DU), 14,975(95%CI:13,047~16,904) for injecting drug users (IDU)
      and 16,767(95%CI:14,602~18,932) for men who have sex with men (MSM). The ratio of
      clients to FSW was 5.74?1, and IDU accounted for 39.5% of the DU population. The
      estimates suggest that FSW account for 0.37% of the female population aged 15-49
      years in Chongqing, and clients of FSW and MSM represent 2.09% and 0.21% of the
      male population aged 15-49 years in the city, respectively. CONCLUSION: NSUM
      provides reasonable population size estimates for FSW, their clients, DU and IDU
      in Chongqing. However, it is likely to underestimate the population size of MSM
      even after adjusting for the transmission effect.

PMID- 23967247
TI  - Development of an efficient targeted cell-SELEX procedure for DNA aptamer
      reagents.
AB  - BACKGROUND: DNA aptamers generated by cell-SELEX offer an attractive alternative
      to antibodies, but generating aptamers to specific, known membrane protein
      targets has proven challenging, and has severely limited the use of aptamers as
      affinity reagents for cell identification and purification. METHODOLOGY: We
      modified the BJAB lymphoblastoma cell line to over-express the murine c-kit cell
      surface receptor. After six rounds of cell-SELEX, high-throughput sequencing and
      bioinformatics analysis, we identified aptamers that bound BJAB cells expressing
      c-kit but not wild-type BJAB controls. One of these aptamers also recognizes c
      kit endogenously expressed by a mast cell line or hematopoietic progenitor cells,
      and specifically blocks binding of the c-kit ligand stem cell factor (SCF). This
      aptamer enables better separation by fluorescence-activated cell sorting (FACS)
      of c-kit(+) hematopoietic progenitor cells from mixed bone marrow populations
      than a commercially available antibody, suggesting that this approach may be
      broadly useful for rapid isolation of affinity reagents suitable for purification
      of other specific cell types. CONCLUSIONS/SIGNIFICANCE: Here we describe a novel
      procedure for the efficient generation of DNA aptamers that bind to specific cell
      membrane proteins and can be used as high affinity reagents. We have named the
      procedure STACS (Specific TArget Cell-SELEX).

PMID- 23967248
TI  - copy number variation analysis in familial BRCA1/2-negative Finnish breast and
      ovarian cancer.
AB  - BACKGROUND: Inherited factors predisposing individuals to breast and ovarian
      cancer are largely unidentified in a majority of families with hereditary breast
      and ovarian cancer (HBOC). We aimed to identify germline copy number variations
      (CNVs) contributing to HBOC susceptibility in the Finnish population. METHODS: A
      cohort of 84 HBOC individuals (negative for BRCA1/2-founder mutations and pre
      screened for the most common breast cancer genes) and 36 healthy controls were
      analysed with a genome-wide SNP array. CNV-affecting genes were further studied
      by Gene Ontology term enrichment, pathway analyses, and database searches to
      reveal genes with potential for breast and ovarian cancer predisposition. CNVs
      that were considered to be important were validated and genotyped in 20
      additional HBOC individuals (6 CNVs) and in additional healthy controls (5 CNVs)
      by qPCR. RESULTS: An intronic deletion in the EPHA3 receptor tyrosine kinase was
      enriched in HBOC individuals (12 of 101, 11.9%) compared with controls (27 of
      432, 6.3%) (OR = 1.96; P = 0.055). EPHA3 was identified in several enriched
      molecular functions including receptor activity. Both a novel intronic deletion
      in the CSMD1 tumor suppressor gene and a homozygous intergenic deletion at 5q15
      were identified in 1 of 101 (1.0%) HBOC individuals but were very rare (1 of 436,
      0.2% and 1 of 899, 0.1%, respectively) in healthy controls suggesting that these
      variants confer disease susceptibility. CONCLUSION: This study reveals new
      information regarding the germline CNVs that likely contribute to HBOC
      susceptibility in Finland. This information may be used to facilitate the genetic
      counselling of HBOC individuals but the preliminary results warrant additional
      studies of a larger study group.

PMID- 23967249
TI  - The therapeutic effect on bone mineral formation from biomimetic zinc containing
      tricalcium phosphate (ZnTCP) in zinc-deficient osteoporotic mice.
AB  - The aim of this study was to evaluate the therapeutic efficacy of biomimetic zinc
      containing tricalcium phosphate (ZnTCP) produced by hydrothermally converting
      calcium carbonate exoskeletons from foraminifera, in the treatment of
      osteoporotic mice. X-Ray powder diffraction showed crystallographic structures
      matching JCPDS profile for tricalcium phosphate. Mass spectroscopy used to
      calculate total composition amount showed similar amount of calcium (5*10(4)
      ug/g) and phosphate (4*10(4) ppm) after conversion and the presence of zinc
      (5.18*10(3) ug/g). In vitro zinc release showed no release in PBS buffer and <1%
      zinc release in 7 days. In vivo evaluation was done in ovariectomized mice by
      implanting the ZnTCP samples in the soft tissues near the right femur bone for
      four weeks. Thirty ddY mice (5 weeks old, average weight of 21 g) were divided
      into six experimental groups (normal, sham, OVX, beta-TCP, ZnTCP and direct
      injection of zinc). CT images were taken every two weeks where the bone mineral
      density (BMD) and bone mineral content (BMC) were calculated by software based on
      CT images. The ZnTCP group exhibits cortical and cancellous bone growth of 45%
      and 20% respectively. While sham, OVX and beta-TCP suffered from bone loss. A
      correlation was made between the significant body weight increase in ZnTCP with
      the significant increase in plasma zinc level compared with OVX. The presented
      results indicate that biomimetic ZnTCP were effective in preventing and treating
      bone loss in osteoporotic mice model. 

PMID- 23967250
TI  - Proteomic and carbonylation profile analysis of rat skeletal muscles following
      acute swimming exercise.
AB  - Previous studies by us and other groups characterized protein expression
      variation following long-term moderate training, whereas the effects of single
      bursts of exercise are less known. Making use of a proteomic approach, we
      investigated the effects of acute swimming exercise (ASE) on protein expression
      and carbonylation patterns in two hind limb muscles: the Extensor Digitorum
      Longus (EDL) and the Soleus, mostly composed of fast-twitch and slow-twitch
      fibres, respectively. Carbonylation is one of the most common oxidative
      modifications of proteins and a marker of oxidative stress. In fact, several
      studies suggest that physical activity and the consequent increase in oxygen
      consumption can lead to increase in reactive oxygen and nitrogen species (RONS)
      production, hence the interest in examining the impact of RONS on skeletal muscle
      proteins following ASE. Results indicate that protein expression is unaffected by
      ASE in both muscle types. Unexpectedly, the protein carbonylation level was
      reduced following ASE. In particular, the analysis found 31 and 5 spots, in
      Soleus and EDL muscles respectively, whose carbonylation is reduced after ASE.
      Lipid peroxidation levels in Soleus were markedly reduced as well. Most of the
      decarbonylated proteins are involved either in the regulation of muscle
      contractions or in the regulation of energy metabolism. A number of hypotheses
      may be advanced to account for such results, which will be addressed in future
      studies. 

PMID- 23967251
TI  - Encoding of situations in the vocal repertoire of piglets (Sus scrofa): a
      comparison of discrete and graded classifications.
AB  - Two important questions in bioacoustics are whether vocal repertoires of animals
      are graded or discrete and how the vocal expressions are linked to the context of
      emission. Here we address these questions in an ungulate species. The vocal
      repertoire of young domestic pigs, Sus scrofa, was quantitatively described based
      on 1513 calls recorded in 11 situations. We described the acoustic quality of
      calls with 8 acoustic parameters. Based on these parameters, the k-means
      clustering method showed a possibility to distinguish either two or five clusters
      although the call types are rather blurred than strictly discrete. The division
      of the vocal repertoire of piglets into two call types has previously been used
      in many experimental studies into pig acoustic communication and the five call
      types correspond well to previously published partial repertoires in specific
      situations. Clear links exist between the type of situation, its putative
      valence, and the vocal expression in that situation. These links can be described
      adequately both with a set of quantitative acoustic variables and through
      categorisation into call types. The information about the situation of emission
      of the calls is encoded through five call types almost as accurately as through
      the full quantitative description. 

PMID- 23967253
TI  - Plasma lipid composition and risk of developing cardiovascular disease.
AB  - AIMS: We tested whether characteristic changes of the plasma lipidome in
      individuals with comparable total lipids level associate with future
      cardiovascular disease (CVD) outcome and whether 23 validated gene variants
      associated with coronary artery disease (CAD) affect CVD associated lipid
      species. METHODS AND RESULTS: Screening of the fasted plasma lipidome was
      performed by top-down shotgun analysis and lipidome compositions compared between
      incident CVD cases (n = 211) and controls (n = 216) from the prospective
      population-based MDC study using logistic regression adjusting for Framingham
      risk factors. Associations with incident CVD were seen for eight lipid species
      (0.21<=q<=0.23). Each standard deviation unit higher baseline levels of two
      lysophosphatidylcholine species (LPC), LPC16?0 and LPC20?4, was associated with a
      decreased risk for CVD (P = 0.024-0.028). Sphingomyelin (SM) 38?2 was associated
      with increased odds of CVD (P = 0.057). Five triglyceride (TAG) species were
      associated with protection (P = 0.031-0.049). LPC16?0 was negatively correlated
      with the carotid intima-media thickness (P = 0.010) and with HbA1c (P = 0.012)
      whereas SM38?2 was positively correlated with LDL-cholesterol (P = 0.0*10(-6))
      and the q-values were good (q<=0.03). The risk allele of 8 CAD-associated gene
      variants showed significant association with the plasma level of several lipid
      species. However, the q-values were high for many of the associations
      (0.015<=q<=0.75). Risk allele carriers of 3 CAD-loci had reduced level of LPC16?0
      and/or LPC 20?4 (P<=0.056). CONCLUSION: Our study suggests that CVD development
      is preceded by reduced levels of LPC16?0, LPC20?4 and some specific TAG species
      and by increased levels of SM38?2. It also indicates that certain lipid species
      are intermediate phenotypes between genetic susceptibility and overt CVD. But it
      is a preliminary study that awaits replication in a larger population because
      statistical significance was lost for the associations between lipid species and
      future cardiovascular events when correcting for multiple testing.

PMID- 23967252
TI  - Regulatory and metabolic networks for the adaptation of Pseudomonas aeruginosa
      biofilms to urinary tract-like conditions.
AB  - Biofilms of the Gram-negative bacterium Pseudomonas aeruginosa are one of the
      major causes of complicated urinary tract infections with detrimental outcome. To
      develop novel therapeutic strategies the molecular adaption strategies of P.
      aeruginosa biofilms to the conditions of the urinary tract were investigated
      thoroughly at the systems level using transcriptome, proteome, metabolome and
      enzyme activity analyses. For this purpose biofilms were grown anaerobically in
      artificial urine medium (AUM). Obtained data were integrated bioinformatically
      into gene regulatory and metabolic networks. The dominating response at the
      transcriptome and proteome level was the adaptation to iron limitation via the
      broad Fur regulon including 19 sigma factors and up to 80 regulated target genes
      or operons. In agreement, reduction of the iron cofactor-dependent nitrate
      respiratory metabolism was detected. An adaptation of the central metabolism to
      lactate, citrate and amino acid as carbon sources with the induction of the
      glyoxylate bypass was observed, while other components of AUM like urea and
      creatinine were not used. Amino acid utilization pathways were found induced,
      while fatty acid biosynthesis was reduced. The high amounts of phosphate found in
      AUM explain the reduction of phosphate assimilation systems. Increased quorum
      sensing activity with the parallel reduction of chemotaxis and flagellum assembly
      underscored the importance of the biofilm life style. However, reduced formation
      of the extracellular polysaccharide alginate, typical for P. aeruginosa biofilms
      in lungs, indicated a different biofilm type for urinary tract infections.
      Furthermore, the obtained quorum sensing response results in an increased
      production of virulence factors like the extracellular lipase LipA and protease
      LasB and AprA explaining the harmful cause of these infections. 

PMID- 23967254
TI  - Can ethnic background differences in children's body composition be explained by
      differences in energy balance-related behaviors? A mediation analysis within the
      energy-project.
AB  - BACKGROUND: In affluent countries, children from non-native ethnicity have in
      general less favourable body composition indicators and energy balance-related
      behaviors (EBRBs) than children from native ethnicity. However, differences
      between countries have been reported. METHODOLOGY/PRINCIPAL FINDINGS: A school
      based survey among 10-12 years old children was conducted in seven European
      countries with a standardized protocol. Weight, height and waist circumference
      were measured; engagement in EBRBs was self-reported. For those countries with
      significant ethnic differences in body composition (Greece and the Netherlands),
      multilevel mediation analyses were conducted, to test the mediating effect of the
      EBRBs in the association between ethnic background and body composition
      indicators. Analyses were adjusted for gender and age, and for parental education
      in a later step. Partial mediation was found for sugared drinks intake and sleep
      duration in the Greek sample, and breakfast in the Dutch sample. A suppression
      effect was found for engagement in sports activites in the Greek sample.
      CONCLUSIONS/SIGNIFICANCE: Ethnic differences in children's body composition were
      partially mediated by differences in breakfast skipping in the Netherlands and
      sugared drinks intake, sports participation and sleep duration in Greece.

PMID- 23967255
TI  - Primary drug-resistant tuberculosis in Hanoi, Viet Nam: present status and risk
      factors.
AB  - INTRODUCTION: Resistance of Mycobacterium tuberculosis (MTB) to anti-tuberculosis
      (TB) drugs presents a serious challenge to TB control worldwide. We investigated
      the status of drug resistance, including multidrug-resistant (MDR) TB, and
      possible risk factors among newly diagnosed TB patients in Hanoi, the capital of
      Viet Nam. METHODS: Clinical and epidemiological information was collected from
      506 newly diagnosed patients with sputum smear- and culture-positive TB, and 489
      (96.6%) MTB isolates were subjected to conventional drug susceptibility testing,
      spoligotyping, and 15-locus variable numbers of tandem repeats typing. Adjusted
      odds ratios (aORs) were calculated to analyze the risk factors for primary drug
      resistance. RESULTS: Of 489 isolates, 298 (60.9%) were sensitive to all drugs
      tested. Resistance to isoniazid, rifampicin, streptomycin, ethambutol, and MDR
      accounted for 28.2%, 4.9%, 28.2%, 2.9%, and 4.5%, respectively. Of 24 isolates
      with rifampicin resistance, 22 (91.7%) were MDR and also resistant to
      streptomycin, except one case. Factors associated with isoniazid resistance
      included living in old urban areas, presence of the Beijing genotype, and
      clustered strains [aOR = 2.23, 95% confidence interval (CI) 1.15-4.35; 1.91, 1.18
      3.10; and 1.69, 1.06-2.69, respectively). The Beijing genotype was also
      associated with streptomycin resistance (aOR = 2.10, 95% CI 1.29-3.40). Human
      immunodeficiency virus (HIV) coinfection was associated with rifampicin
      resistance and MDR (aOR = 5.42, 95% CI 2.07-14.14; 6.23, 2.34-16.58,
      respectively). CONCLUSION: Isoniazid and streptomycin resistance was observed in
      more than a quarter of TB patients without treatment history in Hanoi.
      Transmission of isoniazid-resistant TB among younger people should be carefully
      monitored in urban areas, where Beijing strains and HIV coinfection are
      prevalent. Choosing an optimal treatment regimen on the basis of the results of
      drug susceptibility tests and monitoring of treatment adherence would minimize
      further development of drug resistance strains.

PMID- 23967256
TI  - High molecular weight forms of mammalian respiratory chain complex II.
AB  - Mitochondrial respiratory chain is organised into supramolecular structures that
      can be preserved in mild detergent solubilisates and resolved by native
      electrophoretic systems. Supercomplexes of respiratory complexes I, III and IV as
      well as multimeric forms of ATP synthase are well established. However, the
      involvement of complex II, linking respiratory chain with tricarboxylic acid
      cycle, in mitochondrial supercomplexes is questionable. Here we show that
      digitonin-solubilised complex II quantitatively forms high molecular weight
      structures (CIIhmw) that can be resolved by clear native electrophoresis. CIIhmw
      structures are enzymatically active and differ in electrophoretic mobility
      between tissues (500 - over 1000 kDa) and cultured cells (400-670 kDa). While
      their formation is unaffected by isolated defects in other respiratory chain
      complexes, they are destabilised in mtDNA-depleted, rho0 cells. Molecular
      interactions responsible for the assembly of CIIhmw are rather weak with the
      complexes being more stable in tissues than in cultured cells. While
      electrophoretic studies and immunoprecipitation experiments of CIIhmw do not
      indicate specific interactions with the respiratory chain complexes I, III or IV
      or enzymes of the tricarboxylic acid cycle, they point out to a specific
      interaction between CII and ATP synthase. 

PMID- 23967257
TI  - Signals can trump rewards in attracting seed-dispersing ants.
AB  - Both rewards and signals are important in mutualisms. In myrmecochory, or seed
      dispersal by ants, the benefits to plants are relatively well studied, but less
      is known about why ants pick up and move seeds. We examined seed dispersal by the
      ant Aphaenogaster rudis of four co-occurring species of plants, and tested
      whether morphology, chemical signaling, or the nutritional quality of fatty seed
      appendages called elaiosomes influenced dispersal rates. In removal trials, ants
      quickly collected diaspores (seeds plus elaiosomes) of Asarum canadense, Trillium
      grandiflorum, and Sanguinaria canadensis, but largely neglected those of T.
      erectum. This discrepancy was not explained by differences in the bulk cost
      benefit ratio, as assessed by the ratio of seed to elaiosome mass. We also
      provisioned colonies with diaspores from one of these four plant species or no
      diaspores as a control. Colonies performed best when fed S. canadensis diaspores,
      worst when fed T. grandiflorum, and intermediately when fed A. canadense, T.
      erectum, or no diaspores. Thus, the nutritional rewards in elaiosomes affected
      colony performance, but did not completely predict seed removal. Instead, high
      levels of oleic acid in T. grandiflorum elaiosomes may explain why ants disperse
      these diaspores even though they reduce ant colony performance. We show for the
      first time that different elaiosome-bearing plants provide rewards of different
      quality to ant colonies, but also that ants appear unable to accurately assess
      reward quality when encountering seeds. Instead, we suggest that signals can
      trump rewards as attractants of ants to seeds. 

PMID- 23967258
TI  - Decreases in electrocardiographic R-wave amplitude and QT interval predict
      myocardial ischemic infarction in Rhesus monkeys with left anterior descending
      artery ligation.
AB  - Clinical studies have demonstrated the predictive values of changes in
      electrocardiographic (ECG) parameters for the preexisting myocardial ischemic
      infarction. However, a simple and early predictor for the subsequent development
      of myocardial infarction during the ischemic phase is of significant value for
      the identification of ischemic patients at high risk. The present study was
      undertaken by using non-human primate model of myocardial ischemic infarction to
      fulfill this gap. Twenty male Rhesus monkeys at age of 2-3 years old were
      subjected to left anterior descending artery ligation. This ligation was
      performed at varying position along the artery so that it produced varying sizes
      of myocardial infarction at the late stage. The ECG recording was undertaken
      before the surgical procedure, at 2 h after the ligation, and 8 weeks after the
      surgery for each animal. The correlation of the changes in the ECG waves in the
      early or the late stage with the myocardial infarction size was analyzed. The R
      wave depression and the QT shortening in the early ischemic stage were found to
      have an inverse correlation with the myocardial infarction size. At the late
      stage, the R wave depression, the QT prolongation, the QRS score, and the ST
      segment elevation were all closely correlated with the developed infarction size.
      The poor R wave progression was identified at both the early ischemic and the
      late infarction stages. Therefore, the present study using non-human primate
      model of myocardial ischemic infarction identified the decreases in the R wave
      and the QT interval as early predictors of myocardial infarction. Validation of
      these parameters in clinical studies would greatly help identifying patients with
      myocardial ischemia at high risk for the subsequent development of myocardial
      infarction. 

PMID- 23967259
TI  - IGF-1-induced enhancement of PRNP expression depends on the negative regulation
      of transcription factor FOXO3a.
AB  - The conformational conversion of the cellular prion protein (PrP(C)) into its
      beta-sheet-rich scrapie isoform (PrP(Sc)) causes fatal prion diseases, which are
      also called transmissible spongiform encephalopathies (TSEs). Recent studies
      suggest that the expression of PrP(C) by the PRNP gene is crucial for the
      development of TSEs. Therefore, the identification of the exogenous and
      endogenous stimulating factors that regulate PRNP expression would help to
      understand the pathogenesis of TSEs. Here, we demonstrate that forkhead box O3a
      (FOXO3a) negatively regulates PRNP expression by binding to the PRNP promoter,
      which is negatively regulated by insulin-like growth factor 1 (IGF-1). Our
      results show that the IGF-1-induced enhancement of PRNP mRNA and protein levels
      is due to the activation of the PI3K-Akt signaling pathway. The activation of Akt
      then induces the phosphorylation of FOXO3a, leading to its translocation from the
      nucleus to the cytoplasm and preventing its binding to the PRNP promoter.
      Treatment with the PI3K-Akt inhibitor LY294002 induces the nuclear retention of
      FOXO3a, which leads to a decrease in PRNP expression. We present a new IGF-1-PI3K
      Akt-FOXO3a pathway, which influences PRNP expression. The results of this work
      are vital for understanding the function of PrP(C) and for future therapeutic
      approaches to human TSEs. 

PMID- 23967260
TI  - Survival of primary human hepatocytes and death of induced pluripotent stem cells
      in media lacking glucose and arginine.
AB  - BACKGROUND: Tumorigenicity is an associated risk for transplantation of
      hepatocytes differentiated from human induced pluripotent stem (hiPS) cells.
      Hepatocytes express the enzymes galactokinase and ornithine transcarbamylase
      (OTC) to aid in their own survival. However, hiPS cells do not express these
      enzymes, and therefore, are not be expected to survive in a medium containing
      galactose and ornithine and lacking glucose and arginine. MATERIALS AND METHODS:
      Real-time quantitative polymerase chain reaction (PCR) was performed to analyze
      the expression of galactokinase 1 (GALK1)1 and GALK2, ornithine
      carbamyltransferase, and phenylalanine hydroxylase (PAH). The hiPS cell line
      201B7 was cultured in hepatocyte selection medium (HSM), which lacks glucose and
      arginine but contains galactose and ornithine. Furthermore, microscopic analysis
      of the cultured cells was performed after hematoxylin and eosin (H&E) staining,
      terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling
      (TUNEL). The hiPS cells were immunostained to assess their pluripotency in HSM.
      In addition, the primary human hepatocytes were cultured with or without hiPS
      cells in HSM. RESULTS: The expression levels of GALK1, GALK2, OTC, and PAH in
      201B7 were 22.2+/-5.0 (average +/- standard deviation), 14.2% +/-1.1%, 1.2% +/
      0.2%, and 8.4% +/-0.7% respectively, compared with those in the adult liver. The
      hiPS cell population diminished when cultured in HSM and completely disappeared
      after 3 days. The cultured cells showed condensation or fragmentation of their
      nuclei, thereby suggesting apoptosis. TUNEL staining confirmed that the cells had
      undergone apoptosis. The 201B7 cells were positive for Nanog, SSEA-4, and TRA-1
      60. The primary human hepatocytes survived when cultured alone in HSM and when co
      cultured with hiPS cells. CONCLUSION: Therefore, HSM is and ideal medium for
      eliminating hiPS cells and purifying hepatocytes without inducing any damage.

PMID- 23967261
TI  - Myostatin and insulin-like growth factor I: potential therapeutic biomarkers for
      pompe disease.
AB  - OBJECTIVE: Myostatin and insulin-like growth factor 1 (IGF-1) are serum markers
      for muscle growth and regeneration. However, their value in the clinical
      monitoring of Pompe disease - a muscle glycogen storage disease - is not known.
      In order to evaluate their possible utility for disease monitoring, we assessed
      the levels of these serum markers in Pompe disease patients receiving enzyme
      replacement therapy (ERT). DESIGN: A case-control study that included 10 patients
      with Pompe disease and 10 gender- and age-matched non-Pompe disease control
      subjects was performed in a referral medical center. Average follow-up duration
      after ERT for Pompe disease patients was 11.7 months (range: 6-23 months).
      Measurements of serum myostatin, IGF-1, and creatine kinase levels were obtained,
      and examinations of muscle pathology were undertaken before and after ERT in the
      patient group. RESULTS: Compared with control subjects, Pompe disease patients
      prior to undergoing ERT had significantly lower serum IGF-1 levels (98.6 ng/ml
      vs. 307.9 ng/ml, p = 0.010) and lower myostatin levels that bordered on
      significance (1.38 ng/ml vs. 3.32 ng/ml, p = 0.075). After ERT, respective
      myostatin and IGF-1 levels in Pompe disease patients increased significantly by
      129% (from 1.38 ng/ml to 3.16 ng/ml, p = 0.047) and 74% (from 98.6 ng/ml to 171.1
      ng/ml, p = 0.013); these values fall within age-matched normal ranges. In
      contrast, myostatin and IGF-1 serum markers did not increase in age-matched
      controls. Follistatin, a control marker unrelated to muscle, increased in both
      Pompe disease patients and control subjects. At the same time, the percentage of
      muscle fibers containing intracytoplasmic vacuoles decreased from 80.0+/-26.4% to
      31.6+/-45.3%. CONCLUSION: The increase in myostatin and IGF-1 levels in Pompe
      disease patients may reflect muscle regeneration after ERT. The role of these
      molecules as potential therapeutic biomarkers in Pompe disease and other
      neuromuscular diseases warrants further study.

PMID- 23967262
TI  - ACTH- and cortisol-associated neutrophil modulation in coronary artery disease
      patients undergoing stent implantation.
AB  - BACKGROUND: Psychosocial stress and activation of neutrophil granulocytes are
      increasingly recognized as major risk factors of coronary artery disease (CAD),
      but the possible relationship of these two factors in CAD patients is largely
      unexplored. Activation of neutrophils was reported to be associated with
      stenting; however, the issue of neutrophil state in connection with percutaneous
      coronary intervention (PCI) is incompletely understood from the aspect of stress
      and its hypothalamic-pituitary-adrenal axis (HPA) background. Thus, we aimed to
      study cortisol- and ACTH-associated changes in granulocyte activation in patients
      undergoing PCI. METHODOLOGY/PRINCIPAL FINDINGS: Blood samples of 21 stable angina
      pectoris (SAP) and 20 acute coronary syndrome (ACS) patients were collected
      directly before (pre-PCI), after (post-PCI) and on the following day of PCI (1d
      PCI). Granulocyte surface L-selectin, CD15 and (neutrophil-specific) lactoferrin
      were analysed by flow cytometry. Plasma cortisol, ACTH, and lactoferrin, IL-6
      were also assayed. In both groups, pre- and post-PCI ratios of lactoferrin
      bearing neutrophils were relatively high, these percentages decreased
      substantially next day; similarly, 1d-PCI plasma lactoferrin was about half of
      the post-PCI value (all p<=0.0001). Post-PCI ACTH was reduced markedly next day,
      especially in ACS group (SAP: p<0.01, ACS: p<=0.0001). In ACS, elevated pre-PCI
      cortisol decreased considerably a day after stenting (p<0.01); in pre-PCI
      samples, cortisol correlated with plasma lactoferrin (r~0.5, p<0.05). In 1d-PCI
      samples of both groups, ACTH showed negative associations with the ratio of
      lactoferrin-bearing neutrophils (SAP: r = -0.601, p<0.005; ACS: r = -0.541,
      p<0.05) and with plasma lactoferrin (SAP: r = -0.435, p<0.05; ACS: r = -0.609,
      p<0.005). CONCLUSIONS/SIGNIFICANCE: Pre- and post-PCI states were associated with
      increased percentage of activated/degranulated neutrophils indicated by elevated
      lactoferrin parameters, the 1d-PCI declines of which were associated with plasma
      ACTH in both groups. The correlation of plasma cortisol with plasma lactoferrin
      in the extremely stressed ACS before stenting, however, suggests an association
      of cortisol with neutrophil activation.

PMID- 23967264
TI  - Metabolic flux analysis during the exponential growth phase of Saccharomyces
      cerevisiae in wine fermentations.
AB  - As a consequence of the increase in global average temperature, grapes with the
      adequate phenolic and aromatic maturity tend to be overripe by the time of
      harvest, resulting in increased sugar concentrations and imbalanced C/N ratios in
      fermenting musts. This fact sets obvious additional hurdles in the challenge of
      obtaining wines with reduced alcohols levels, a new trend in consumer demands. It
      would therefore be interesting to understand Saccharomyces cerevisiae physiology
      during the fermentation of must with these altered characteristics. The present
      study aims to determine the distribution of metabolic fluxes during the yeast
      exponential growth phase, when both carbon and nitrogen sources are in excess,
      using continuous cultures. Two different sugar concentrations were studied under
      two different winemaking temperature conditions. Although consumption and
      production rates for key metabolites were severely affected by the different
      experimental conditions studied, the general distribution of fluxes in central
      carbon metabolism was basically conserved in all cases. It was also observed that
      temperature and sugar concentration exerted a higher effect on the pentose
      phosphate pathway and glycerol formation than on glycolysis and ethanol
      production. Additionally, nitrogen uptake, both quantitatively and qualitatively,
      was strongly influenced by environmental conditions. This work provides the most
      complete stoichiometric model used for Metabolic Flux Analysis of S. cerevisiae
      in wine fermentations employed so far, including the synthesis and release of
      relevant aroma compounds and could be used in the design of optimal nitrogen
      supplementation of wine fermentations. 

PMID- 23967263
TI  - Right occipital cortex activation correlates with superior odor processing
      performance in the early blind.
AB  - Using functional magnetic resonance imaging (fMRI) in ten early blind humans, we
      found robust occipital activation during two odor-processing tasks
      (discrimination or categorization of fruit and flower odors), as well as during
      control auditory-verbal conditions (discrimination or categorization of fruit and
      flower names). We also found evidence for reorganization and specialization of
      the ventral part of the occipital cortex, with dissociation according to stimulus
      modality: the right fusiform gyrus was most activated during olfactory conditions
      while part of the left ventral lateral occipital complex showed a preference for
      auditory-verbal processing. Only little occipital activation was found in sighted
      subjects, but the same right-olfactory/left-auditory-verbal hemispheric
      lateralization was found overall in their brain. This difference between the
      groups was mirrored by superior performance of the blind in various odor
      processing tasks. Moreover, the level of right fusiform gyrus activation during
      the olfactory conditions was highly correlated with individual scores in a
      variety of odor recognition tests, indicating that the additional occipital
      activation may play a functional role in odor processing. 

PMID- 23967265
TI  - Influence of contrast and coherence on the temporal dynamics of binocular motion
      rivalry.
AB  - Levelt's four propositions (L1-L4), which characterize the relation between
      changes in "stimulus strength" in the two eyes and percept alternations, are
      considered benchmark for binocular rivalry models. It was recently demonstrated
      that adaptation mutual-inhibition models of binocular rivalry capture L4 only in
      a limited range of input strengths, predicting an increase rather than a decrease
      in dominance durations with increasing stimulus strength for weak stimuli. This
      observation challenges the validity of those models, but possibly L4 itself is
      invalid. So far, L1-L4 have been tested mainly by varying the contrast of static
      stimuli, but since binocular rivalry breaks down at low contrasts, it has been
      difficult to study L4. To circumvent this problem, and to test if the recent
      revision of L2 has more general validity, we studied changes in binocular rivalry
      evoked by manipulating coherence of oppositely-moving random-dot stimuli in the
      two eyes, and compared them against the effects of stimulus contrast. Thirteen
      human observers participated. Both contrast and coherence manipulations in one
      eye produced robust changes in both eyes; dominance durations of the eye
      receiving the stronger stimulus increased while those of the other eye decreased,
      albeit less steeply. This is inconsistent with L2 but supports its revision. When
      coherence was augmented in both eyes simultaneously, dominance durations first
      increased at low coherence, and then decreased for further increases in
      coherence. The same held true for the alternation periods. The initial increase
      in dominance durations was absent in the contrast experiments, but with coherence
      manipulations, rivalry could be tested at much lower stimulus strengths. Thus, we
      found that L4, like L2, is only valid in a limited range of stimulus strengths.
      Outside that range, the opposite is true. Apparent discrepancies between contrast
      and coherence experiments could be fully reconciled with adaptation mutual
      inhibition models using a simple input transfer-function. 

PMID- 23967266
TI  - Ectopic blood supply of hepatocellular carcinoma as depicted by angiography with
      computed tomography: associations with morphological features and therapeutic
      history.
AB  - OBJECTIVE: To investigate the associations of ectopic blood supply of
      hepatocellular carcinoma (HCC) with its morphological features and therapeutic
      history. METHODS: Three hundred and six patients with 373 HCC lesions were
      enrolled in this study, and underwent biphasic contrast-enhanced scans on a 64
      section MDCT. The anatomy of ectopic blood supply, morphological characteristics
      of HCC including the size, location and pseudocapsule, and history of
      transcatheter arterial chemoembolization (TACE) therapy were quantitively
      assessed and statistically analyzed. RESULTS: Ectopic blood supply was found in
      30.8% (115/373) lesions. The ectopic arteries were predominantly composed of
      inferior phrenic artery (86/115) followed by left and right gastric artery
      (25/115). Tumor size, location, status of pseudocapsule, and history of TACE
      therapy could impact the origination of ectopic arteries (all p<0.05).
      CONCLUSION: The ectopic feeding arteries of HCC predominantly composed of the
      perihepatic arteries are associated with the morphological features of the tumor
      and therapeutic history.

PMID- 23967267
TI  - Loss of the anorexic response to systemic 5-aminoimidazole-4-carboxamide-1-beta-D
      ribofuranoside administration despite reducing hypothalamic AMP-activated protein
      kinase phosphorylation in insulin-deficient rats.
AB  - This study tested whether chronic systemic administration of 5-aminoimidazole-4
      carboxamide-1-beta-D-ribofuranoside (AICAR) could attenuate hyperphagia, reduce
      lean and fat mass losses, and improve whole-body energy homeostasis in insulin
      deficient rats. Male Wistar rats were first rendered diabetic through
      streptozotocin (STZ) administration and then intraperitoneally injected with
      AICAR for 7 consecutive days. Food and water intake, ambulatory activity, and
      energy expenditure were assessed at the end of the AICAR-treatment period. Blood
      was collected for circulating leptin measurement and the hypothalami were
      extracted for the determination of suppressor of cytokine signaling 3 (SOCS3)
      content, as well as the content and phosphorylation of AMP-kinase (AMPK), acetyl
      CoA carboxylase (ACC), and the signal transducer and activator of transcription 3
      (STAT3). Rats were thoroughly dissected for adiposity and lean body mass (LBM)
      determinations. In non-diabetic rats, despite reducing adiposity, AICAR increased
      (~1.7-fold) circulating leptin and reduced hypothalamic SOCS3 content and food
      intake by 67% and 25%, respectively. The anorexic effect of AICAR was lost in
      diabetic rats, even though hypothalamic AMPK and ACC phosphorylation markedly
      decreased in these animals. Importantly, hypothalamic SOCS3 and STAT3 levels
      remained elevated and reduced, respectively, after treatment of insulin-deficient
      rats with AICAR. Diabetic rats were lethargic and displayed marked losses of fat
      and LBM. AICAR treatment increased ambulatory activity and whole-body energy
      expenditure while also attenuating diabetes-induced fat and LBM losses. In
      conclusion, AICAR did not reverse hyperphagia, but it promoted anti-catabolic
      effects on skeletal muscle and fat, enhanced spontaneous physical activity, and
      improved the ability of rats to cope with the diabetes-induced dysfunctional
      alterations in glucose metabolism and whole-body energy homeostasis.

PMID- 23967268
TI  - Cigarette smoke modulates vascular smooth muscle phenotype: implications for
      carotid and cerebrovascular disease.
AB  - BACKGROUND: The role of smooth muscle cell (SMC) phenotypic modulation in the
      cerebral circulation and pathogenesis of stroke has not been determined.
      Cigarette smoke is a major risk factor for atherosclerosis, but potential
      mechanisms are unclear, and its role in SMC phenotypic modulation has not been
      established. METHODS AND RESULTS: In cultured cerebral vascular SMCs, exposure to
      cigarette smoke extract (CSE) resulted in decreased promoter activity and mRNA
      expression of key SMC contractile genes (SM-alpha-actin, SM-22alpha, SM-MHC) and
      the transcription factor myocardin in a dose-dependent manner. CSE also induced
      pro-inflammatory/matrix remodeling genes (MCP-1, MMPs, TNF-alpha, IL-1beta, NF
      kappaB). CSE increased expression of KLF4, a known regulator of SMC
      differentiation, and siKLF4 inhibited CSE induced suppression of SMC contractile
      genes and myocardin and activation of inflammatory genes. These mechanisms were
      confirmed in vivo following exposure of rat carotid arteries to CSE. Chromatin
      immune-precipitation assays in vivo and in vitro demonstrated that CSE promotes
      epigenetic changes with binding of KLF4 to the promoter regions of myocardin and
      SMC marker genes and alterations in promoter acetylation and methylation.
      CONCLUSION: CSE exposure results in phenotypic modulation of cerebral SMC through
      myocardin and KLF4 dependent mechanisms. These results provides a mechanism by
      which cigarette smoke induces a pro-inflammatory/matrix remodeling phenotype in
      SMC and an important pathway for cigarette smoke to contribute to atherosclerosis
      and stroke.

PMID- 23967269
TI  - A genome-wide association study of total serum and mite-specific IgEs in asthma
      patients.
AB  - Immunoglobulin E (IgE) is one of the central players in asthma and allergic
      diseases. Although the serum IgE level, a useful endophenotype, is generally
      increased in patients with asthma, genetic factors influencing IgE regulation in
      asthma are still not fully understood. To identify the genetic variations
      associated with total serum and mite-specific IgEs in asthmatics, a genome-wide
      association study (GWAS) of 657,366 single nucleotide polymorphisms (SNPs) was
      performed in 877 Korean asthmatics. This study found that several new genes might
      be associated with total IgE in asthmatics, such as CRIM1 (rs848512, P = 1.18*10(
      6); rs711254, P = 6.73*10(-6)), ZNF71 (rs10404342, P = 7.60*10(-6)), TLN1
      (rs4879926, P = 7.74*10(-6)), and SYNPO2 (rs1472066, P = 8.36*10(-6); rs1038770,
      P = 8.66*10(-6)). Regarding the association of specific IgE to house dust mites,
      it was observed that intergenic SNPs nearby to OPRK1 and LOC730217 might be
      associated with Dermatophagoides pteronyssinus (D.p.) and Dermatophagoides
      farinae (D.f.) in asthmatics, respectively. In further pathway analysis, the
      phosphatidylinositol signaling system and adherens junction pathways were
      estimated to play a role in the regulation of total IgE levels in asthma.
      Although functional evaluations and replications of these results in other
      populations are needed, this GWAS of serum IgE in asthmatics could facilitate
      improved understanding of the role of the newly identified genetic variants in
      asthma and its related phenotypes. 

PMID- 23967270
TI  - A cell system for phenotypic screening of modifiers of SMN2 gene expression and
      function.
AB  - Spinal muscular atrophy (SMA) is an inherited neurodegenerative disease caused by
      homozygous inactivation of the SMN1 gene and reduced levels of the survival motor
      neuron (SMN) protein. Since higher copy numbers of the nearly identical SMN2 gene
      reduce disease severity, to date most efforts to develop a therapy for SMA have
      focused on enhancing SMN expression. Identification of alternative therapeutic
      approaches has partly been hindered by limited knowledge of potential targets and
      the lack of cell-based screening assays that serve as readouts of SMN function.
      Here, we established a cell system in which proliferation of cultured mouse
      fibroblasts is dependent on functional SMN produced from the SMN2 gene. To do so,
      we introduced the entire human SMN2 gene into NIH3T3 cell lines in which
      regulated knockdown of endogenous mouse Smn severely decreases cell
      proliferation. We found that low SMN2 copy number has modest effects on the cell
      proliferation phenotype induced by Smn depletion, while high SMN2 copy number is
      strongly protective. Additionally, cell proliferation correlates with the level
      of SMN activity in small nuclear ribonucleoprotein assembly. Following
      miniaturization into a high-throughput format, our cell-based phenotypic assay
      accurately measures the beneficial effects of both pharmacological and genetic
      treatments leading to SMN upregulation. This cell model provides a novel platform
      for phenotypic screening of modifiers of SMN2 gene expression and function that
      act through multiple mechanisms, and a powerful new tool for studies of SMN
      biology and SMA therapeutic development. 

PMID- 23967271
TI  - If you've got it, flaunt it: humans flaunt attractive partners to enhance their
      status and desirability.
AB  - Mating decisions are influenced by conspecifics' mate choices in many species
      including humans. Recent research has shown that women are more attracted to men
      with attractive putative partners than those with less attractive partners. We
      integrate these findings with traditional accounts of social signaling and test
      five hypotheses derived from it. In our study, 64 men and 75 women were paired
      with attractive and unattractive opposite-sex putative partners and asked whether
      they would prefer to give surveys to peers or to older adults. Consistent with
      predictions, both men and women wanted to show off (flaunt) attractive partners
      by administering surveys to peers and both men and women wanted to hide (conceal)
      unattractive partners from peers by administering surveys to older adults. These
      decisions were mediated by how participants expected others to evaluate their
      status and desirability when they administered the surveys, consistent with
      partners serving a social signaling function in humans. 

PMID- 23967272
TI  - Differential associations of depressive symptom dimensions with cardio-vascular
      disease in the community: results from the Gutenberg health study.
AB  - A current model suggested that the somatic symptom dimension accounts for the
      adverse effect of depression in patients with coronary heart disease (CHD). In
      order to test this model we sought to determine in a large population-based
      sample how symptom dimensions of depression are associated with CHD, biomarkers
      and traditional risk factors. The associations of cognitive and somatic symptom
      dimensions of depression with CHD, risk factors, endothelial function, and
      biomarkers of inflammation and myocardial stress were analyzed cross-sectionally
      in a sample of n = 5000 Mid-Europeans aged 35-74 years from the Gutenberg Health
      Study (GHS). Only the somatic symptom dimension of depression was associated with
      CHD, biomarkers (inflammation, vascular function) and cardio-vascular risk
      factors. When multivariable adjustment was applied by demographic and
      cardiovascular risk factors, the weak associations of the somatic symptom
      dimension with the biomarkers disappeared. However, the associations of the
      somatic symptom dimension with CHD, myocardial infarction, obesity, dyslipidemia
      and family history of myocardial infarction remained. Both dimensions of
      depression were independently associated with a previous diagnosis of depression
      and distressed personality (type D). Thus, our results partly confirm current
      models: Somatic, but not cognitive-affective symptom dimensions are responsible
      for the association between depression and CHD, inflammation, vascular function
      and cardiovascular risk factors in the general population. However, our findings
      challenge the assumptions that somatic depression might be due to inflammation or
      vascular dysfunction as consequence of progressed atherosclerotic disease. They
      rather emphasize a close interplay with life-style factors and with a family
      history of MI. 

PMID- 23967273
TI  - Cerebral cell renewal in adult mice controls the onset of obesity.
AB  - The hypothalamus plays a crucial role in the control of the energy balance and
      also retains neurogenic potential into adulthood. Recent studies have reported
      the severe alteration of the cell turn-over in the hypothalamus of obese animals
      and it has been proposed that a neurogenic deficiency in the hypothalamus could
      be involved in the development of obesity. To explore this possibility, we
      examined hypothalamic cell renewal during the homeostatic response to dietary fat
      in mice, i.e., at the onset of diet-induced obesity. We found that switching to
      high-fat diet (HFD) accelerated cell renewal in the hypothalamus through a local,
      rapid and transient increase in cell proliferation, peaking three days after
      introducing the HFD. Blocking HFD-induced cell proliferation by central delivery
      of an antimitotic drug prevented the food intake normalization observed after HFD
      introduction and accelerated the onset of obesity. This result showed that HFD
      induced dividing brain cells supported an adaptive anorectic function. In
      addition, we found that the percentage of newly generated neurons adopting a POMC
      phenotype in the arcuate nucleus was increased by HFD. This observation suggested
      that the maturation of neurons in feeding circuits was nutritionally regulated to
      adjust future energy intake. Taken together, these results showed that adult
      cerebral cell renewal was remarkably responsive to nutritional conditions. This
      constituted a physiological trait required to prevent severe weight gain under
      HFD. Hence this report highlighted the amazing plasticity of feeding circuits and
      brought new insights into our understanding of the nutritional regulation of the
      energy balance. 

PMID- 23967274
TI  - Protective effects of metallothionein on isoniazid and rifampicin-induced
      hepatotoxicity in mice.
AB  - Isoniazid (INH) and Rifampicin (RFP) are widely used in the world for the
      treatment of tuberculosis, but the hepatotoxicity is a major concern during
      clinical therapy. Previous studies showed that these drugs induced oxidative
      stress in liver, and several antioxidants abated this effect. Metallothionein
      (MT), a member of cysteine-rich protein, has been proposed as a potent
      antioxidant. This study attempts to determine whether endogenous expression of MT
      protects against INH and RFP-induced hepatic oxidative stress in mice. Wild type
      (MT+/+) and MT-null (MT-/-) mice were treated intragastrically with INH (150
      mg/kg), RFP (300 mg/kg), or the combination (150 mg/kg INH +300 mg/kg RFP) for 21
      days. The results showed that MT-/- mice were more sensitive than MT+/+ mice to
      INH and RFP-induced hepatic injuries as evidenced by hepatic histopathological
      alterations, increased serum AST levels and liver index, and hepatic oxidative
      stress as evidenced by the increase of MDA production and the change of liver
      antioxidant status. Furthermore, INH increased the protein expression of hepatic
      CYP2E1 and INH/RFP (alone or in combination) decreased the expression of hepatic
      CYP1A2. These findings clearly demonstrate that basal MT provides protection
      against INH and RFP-induced toxicity in hepatocytes. The CYP2E1 and CYP1A2 were
      involved in the pathogenesis of INH and RFP-induced hepatotoxicity. 

PMID- 23967275
TI  - Silent ischemic heart disease and pericardial fat volume in HIV-infected
      patients: a case-control myocardial perfusion scintigraphy study.
AB  - OBJECTIVES: to determine the prevalence of asymptomatic ischemic heart disease
      (IHD) in HIV patients by myocardial perfusion scintigraphy (MPS) and to determine
      the value of coronary artery calcium score (CACS), carotid intima-media thickness
      (cIMT) and pericardial fat volume as screening tools for detection of IHD in
      subjects with HIV. BACKGROUND: Patients with HIV seem prone to early development
      of IHD. METHODS: 105 consecutive HIV patients (mean age 47.4 years; mean duration
      of HIV 12.3 years; mean CD4+ cell count 636*106/L; all receiving antiretroviral
      therapy) and 105 controls matched for age, gender and smoking status, without
      history of IHD were recruited. MPS, CACS, cIMT, pericardial fat volume, and
      cardiovascular risk scores were measured. RESULTS: HIV patients demonstrated
      higher prevalence of perfusion defects than controls (18% vs. 0%; p<0.001)
      despite similar risk scores. Of HIV patients with perfusion defects, 42% had a
      CACS = 0. CACS and cIMT were similar in HIV patients and controls. HIV patients
      on average had 35% increased pericardial fat volume and increased concentration
      of biomarkers of atherosclerosis in the blood. HIV patients with myocardial
      perfusion defects had increased pericardial fat volume compared with HIV patients
      without perfusion defects (314+/-43 vs. 189+/-12 mL; p<0.001). CONCLUSIONS: HIV
      patients had an increased prevalence of silent IHD compared to controls as
      demonstrated by MPS. The finding was strongly associated with pericardial fat
      volume, whereas cardiovascular risk scores, cIMT and CACS seem less useful as
      screening tools for detection of myocardial perfusion defects in HIV patients.

PMID- 23967276
TI  - Hydroxyurea use and hospitalization trends in a comprehensive pediatric sickle
      cell program.
AB  - BACKGROUND: A decline in hospitalizations and pain episodes among those with
      sickle cell disease (SCD) who take hydroxyurea (HU) has been shown when compared
      to pre-HU patterns but paradoxically, when compared to those who have never been
      treated, HU recipients often have more frequent hospitalizations. This analysis
      evaluates the impact of increasing usage of HU on trends in hospitalizations and
      blood transfusions within a large SCD treatment program. METHODS: Eligibility was
      restricted to patients with Hb SS or Hb Sbeta0-thalassemia who were 2-18 years
      old between 2006-2010 and received care at St. Jude Children's Research Hospital
      (N = 508). Hospitalizations and blood transfusions were calculated for each of
      the years under study for those exposed and never exposed to HU. Differences in
      number of hospitalizations before and after HU initiation were compared. RESULTS:
      The proportion of patients receiving HU increased by 4% per year on average. In
      the HU exposed group, a modest decline in mean per-patient hospitalizations and
      per-patient hospital days occurred, while those never exposed to HU trended
      toward a slight increase over time. Rates of blood transfusions declined among
      those on HU but not in patients never exposed to HU. Patients on HU had a median
      of one fewer hospital admission in the year after initiation of HU, compared to
      the year prior. Two deaths occurred in the patient population, both of whom were
      not exposed to HU. CONCLUSIONS: Increasing usage of HU was concurrent with
      decreased hospitalization rates and blood transfusions. Our results support the
      utility of HU on decreasing hospitalizations and transfusions for patients with
      SCD outside of the clinical trial setting.

PMID- 23967277
TI  - Integration of steady-state and temporal gene expression data for the inference
      of gene regulatory networks.
AB  - We develop a new regression algorithm, cMIKANA, for inference of gene regulatory
      networks from combinations of steady-state and time-series gene expression data.
      Using simulated gene expression datasets to assess the accuracy of reconstructing
      gene regulatory networks, we show that steady-state and time-series data sets can
      successfully be combined to identify gene regulatory interactions using the new
      algorithm. Inferring gene networks from combined data sets was found to be
      advantageous when using noisy measurements collected with either lower sampling
      rates or a limited number of experimental replicates. We illustrate our method by
      applying it to a microarray gene expression dataset from human umbilical vein
      endothelial cells (HUVECs) which combines time series data from treatment with
      growth factor TNF and steady state data from siRNA knockdown treatments. Our
      results suggest that the combination of steady-state and time-series datasets may
      provide better prediction of RNA-to-RNA interactions, and may also reveal
      biological features that cannot be identified from dynamic or steady state
      information alone. Finally, we consider the experimental design of genomics
      experiments for gene regulatory network inference and show that network inference
      can be improved by incorporating steady-state measurements with time-series data.

PMID- 23967278
TI  - Sexually dimorphic, developmental, and chronobiological behavioral profiles of a
      mouse mania model.
AB  - Bipolar disorders are heritable psychiatric conditions often abstracted by
      separate animal models for mania and depression. The principal mania models
      involve transgenic manipulations or treatment with stimulants. An additional
      approach involves analysis of naturally occurring mania models including an
      inbred strain our lab has recently characterized, the Madison (MSN) mouse strain.
      These mice show a suite of behavioral and neural genetic alterations analogous to
      manic aspects of bipolar disorders. In the current study, we extended the MSN
      strain's behavioral phenotype in new directions by examining in-cage locomotor
      activity. We found that MSN activity presentation is sexually dimorphic, with MSN
      females showing higher in-cage activity than MSN males. When investigating
      development, we found that MSN mice display stable locomotor hyperactivity
      already observable when first assayed at 28 days postnatal. Using continuous
      monitoring and analysis for 1 month, we did not find evidence of spontaneous
      bipolarism in MSN mice. However, we did find that the MSN strain displayed an
      altered diurnal activity profile, getting up earlier and going to sleep earlier
      than control mice. Long photoperiods were associated with increased in-cage
      activity in MSN, but not in the control strain. The results of these experiments
      reinforce the face validity of the MSN strain as a complex mania model, adding
      sexual dimorphism, an altered diurnal activity profile, and seasonality to the
      suite of interesting dispositional phenomena related to mania seen in MSN mice. 

PMID- 23967279
TI  - Reciprocal activation of transcription factors underlies the dichotomy between
      proliferation and invasion of glioma cells.
AB  - Histology of malignant glioma depicts dense proliferative areas rich in
      angiogenesis as well as dissemination of neoplastic cells into adjacent brain
      tissue. Although the mechanisms that trigger transition from proliferative to
      invasive phenotypes are complex, the dichotomy of cell proliferation and
      migration, the "Go or Grow" hypothesis, argues for specific and coordinated
      regulation of these phenotypes. We investigated transcriptional elements that
      accompany the phenotypes of migration and proliferation, and consider the
      therapeutic significance of the "Go or Grow" hypothesis. Interrogation of matched
      core and rim regions from human glioblastoma biopsy specimens in situ (n = 44)
      revealed higher proliferation (Ki67 labeling index) in cells residing at the core
      compared to the rim. Profiling activated transcription factors in a panel of
      migration-activated versus migration-restricted GBM cells portrayed strong NF
      kappaB activity in the migratory cell population. In contrast, increased c-Myc
      activity was found in migration-restricted proliferative cells. Validation of
      transcriptional activity by NF-kappaB- or c-Myc-driven GFP or RFP, respectively,
      showed an increased NF-kappaB activity in the active migrating cells, whereas the
      proliferative, migration restricted cells displayed increased c-Myc activity.
      Immunohistochemistry on clinical specimens validated a robust phosphorylated c
      Myc staining in tumor cells at the core, whereas increased phosphorylated NF
      kappaB staining was detected in the invasive tumor cells at the rim. Functional
      genomics revealed that depletion of c-Myc expression by siRNA oligonucleotides
      reduced cell proliferation in vitro, but surprisingly, cell migration was
      enhanced significantly. Conversely, inhibition of NF-kappaB by pharmacological
      inhibitors, SN50 or BAY-11, decreased both cell migration in vitro and invasion
      ex vivo. Notably, inhibition of NF-kappaB was found to have no effect on the
      proliferation rate of glioma cells. These findings suggest that the reciprocal
      and coordinated suppression/activation of transcription factors, such as c-Myc
      and NF-kappaB may underlie the shift of glioma cells from a "growing-to-going"
      phenotype. 

PMID- 23967280
TI  - Females paired with new and heavy mates reduce intra-clutch differences in
      resource allocation.
AB  - Reproductive investment affects both offspring and parental fitness and
      influences the evolution of life histories. Females may vary their overall
      primary reproductive effort in relation to the phenotypic characteristics of
      their mate. However, the effects of male quality on differential resource
      allocation within clutches have been largely neglected despite the potential
      implications for mate choice and population dynamics, especially in species
      exhibiting biparental care and brood reduction. Female southern rockhopper
      penguins Eudyptes chrysocome paired with heavy mates reduced intra-clutch
      variation in egg and albumen masses. Females paired with new mates also reduced
      intra-clutch variation in yolk androgen levels. Since both an increased mass and
      increased androgen concentrations positively influence chick survival under
      sibling competition, the chances of fledging the whole clutch are likely to be
      higher for newly formed pairs with heavy males than for previously formed pairs
      with light males. Interestingly, total clutch provisioning did not vary with male
      quality. We show for the first time that females vary intra-clutch variation in
      resource allocation according to male quality. In species with brood reduction,
      it may be more adaptive for females to modulate the distribution of resources
      within the clutch according to breeding conditions, than to change their total
      clutch provisioning. 

PMID- 23967282
TI  - Seasonal, diurnal and vertical variation of chlorophyll fluorescence on
      Phyllostachys humilis in Ireland.
AB  - In recent years, temperate bamboo species have been introduced in Europe not only
      as an ornamental plant, but also as a new biomass crop. To measure adaptation
      stress of bamboo to the climate of Western Europe, chlorophyll fluorescence was
      measured on a diurnal and seasonal basis in Ballyboughal, Co. Dublin, Ireland.
      Measurements were attained on the leaves of each node of Phyllostachys humilis.
      The most frequently used parameter in chlorophyll fluorescence is the
      photosynthetic efficiency (Fv/Fm). A seasonal dip - as well as a larger variation
      - of Fv/Fm in spring compared to the rest of the year was observed. Over the
      year, the upper leaves of the plant perform better than the bottom leaves. These
      findings were linked to environmental factors such as light intensity, air
      temperature and precipitation, as increased light intensities, decreasing air
      temperatures and their interactions, also with precipitation levels have an
      effect on the photosynthetic efficiency (Fv/Fm) in these plants. 

PMID- 23967281
TI  - Multiple susceptibility loci for radiation-induced mammary tumorigenesis in
      F2[Dahl S x R]-intercross rats.
AB  - Although two major breast cancer susceptibility genes, BRCA1 and BRCA2, have been
      identified accounting for 20% of breast cancer genetic risk, identification of
      other susceptibility genes accounting for 80% risk remains a challenge due to the
      complex, multi-factorial nature of breast cancer. Complexity derives from
      multiple genetic determinants, permutations of gene-environment interactions,
      along with presumptive low-penetrance of breast cancer predisposing genes, and
      genetic heterogeneity of human populations. As with other complex diseases,
      dissection of genetic determinants in animal models provides key insight since
      genetic heterogeneity and environmental factors can be experimentally controlled,
      thus facilitating the detection of quantitative trait loci (QTL). We therefore,
      performed the first genome-wide scan for loci contributing to radiation-induced
      mammary tumorigenesis in female F2-(Dahl S x R)-intercross rats. Tumorigenesis
      was measured as tumor burden index (TBI) after induction of rat mammary tumors at
      forty days of age via 127Cs-radiation. We observed a spectrum of tumor latency,
      size-progression, and pathology from poorly differentiated ductal adenocarcinoma
      to fibroadenoma, indicating major effects of gene-environment interactions. We
      identified two mammary tumorigenesis susceptibility quantitative trait loci (Mts
      QTLs) with significant linkage: Mts-1 on chromosome-9 (LOD-2.98) and Mts-2 on
      chromosome-1 (LOD-2.61), as well as two Mts-QTLs with suggestive linkage: Mts-3
      on chromosome-5 (LOD-1.93) and Mts-4 on chromosome-18 (LOD-1.54). Interestingly,
      Chr9-Mts-1, Chr5-Mts-3 and Chr18-Mts-4 QTLs are unique to irradiation-induced
      mammary tumorigenesis, while Chr1-Mts-2 QTL overlaps with a mammary cancer
      susceptibility QTL (Mcs 3) reported for 7,12-dimethylbenz-[alpha]antracene (DMBA)
      induced mammary tumorigenesis in F2[COP x Wistar-Furth]-intercross rats.
      Altogether, our results suggest at least three distinct susceptibility QTLs for
      irradiation-induced mammary tumorigenesis not detected in genetic studies of
      chemically-induced and hormone-induced mammary tumorigenesis. While more study is
      needed to identify the specific Mts-gene variants, elucidation of specific
      variant(s) could establish causal gene pathways involved in mammary tumorigenesis
      in humans, and hence novel pathways for therapy.

PMID- 23967283
TI  - Metabolic reprogramming for producing energy and reducing power in fumarate
      hydratase null cells from hereditary leiomyomatosis renal cell carcinoma.
AB  - Fumarate hydratase (FH)-deficient kidney cancer undergoes metabolic remodeling,
      with changes in mitochondrial respiration, glucose, and glutamine metabolism.
      These changes represent multiple biochemical adaptations in glucose and fatty
      acid metabolism that supports malignant proliferation. However, the metabolic
      linkages between altered mitochondrial function, nucleotide biosynthesis and
      NADPH production required for proliferation and survival have not been
      elucidated. To characterize the alterations in glycolysis, the Krebs cycle and
      the pentose phosphate pathways (PPP) that either generate NADPH (oxidative) or do
      not (non-oxidative), we utilized [U-(13)C]-glucose, [U-(13)C,(15)N]-glutamine,
      and [1,2- (13)C2]-glucose tracers with mass spectrometry and NMR detection to
      track these pathways, and measured the oxygen consumption rate (OCR) and
      extracellular acidification rate (ECAR) of growing cell lines. This metabolic
      reprogramming in the FH null cells was compared to cells in which FH has been
      restored. The FH null cells showed a substantial metabolic reorganization of
      their intracellular metabolic fluxes to fulfill their high ATP demand, as
      observed by a high rate of glucose uptake, increased glucose turnover via
      glycolysis, high production of glucose-derived lactate, and low entry of glucose
      carbon into the Krebs cycle. Despite the truncation of the Krebs cycle associated
      with inactivation of fumarate hydratase, there was a small but persistent level
      of mitochondrial respiration, which was coupled to ATP production from oxidation
      of glutamine-derived alpha-ketoglutarate through to fumarate. [1,2- (13)C2]
      glucose tracer experiments demonstrated that the oxidative branch of PPP
      initiated by glucose-6-phosphate dehydrogenase activity is preferentially
      utilized for ribose production (56-66%) that produces increased amounts of ribose
      necessary for growth and NADPH. Increased NADPH is required to drive reductive
      carboxylation of alpha-ketoglutarate and fatty acid synthesis for rapid
      proliferation and is essential for defense against increased oxidative stress.
      This increased NADPH producing PPP activity was shown to be a strong consistent
      feature in both fumarate hydratase deficient tumors and cell line models. 

PMID- 23967284
TI  - Inter-vertebral flexibility of the ostrich neck: implications for estimating
      sauropod neck flexibility.
AB  - The flexibility and posture of the neck in sauropod dinosaurs has long been
      contentious. Improved constraints on sauropod neck function will have major
      implications for what we know of their foraging strategies, ecology and overall
      biology. Several hypotheses have been proposed, based primarily on osteological
      data, suggesting different degrees of neck flexibility. This study attempts to
      assess the effects of reconstructed soft tissues on sauropod neck flexibility
      through systematic removal of muscle groups and measures of flexibility of the
      neck in a living analogue, the ostrich (Struthio camelus). The possible effect of
      cartilage on flexibility is also examined, as this was previously overlooked in
      osteological estimates of sauropod neck function. These comparisons show that
      soft tissues are likely to have limited the flexibility of the neck beyond the
      limits suggested by osteology alone. In addition, the inferred presence of
      cartilage, and varying the inter-vertebral spacing within the synovial capsule,
      also affect neck flexibility. One hypothesis proposed that flexibility is
      constrained by requiring a minimum overlap between successive zygapophyses
      equivalent to 50% of zygapophyseal articular surface length (ONP50). This
      assumption is tested by comparing the maximum flexibility of the articulated
      cervical column in ONP50 and the flexibility of the complete neck with all
      tissues intact. It is found that this model does not adequately convey the
      pattern of flexibility in the ostrich neck, suggesting that the ONP50 model may
      not be useful in determining neck function if considered in isolation from
      myological and other soft tissue data. 

PMID- 23967285
TI  - No evidence for a role of adipose tissue-derived serum amyloid a in the
      development of insulin resistance or obesity-related inflammation in hSAA1(+/-)
      transgenic mice.
AB  - Obesity is associated with a low-grade inflammation including moderately
      increased serum levels of the acute phase protein serum amyloid A (SAA). In
      obesity, SAA is mainly produced from adipose tissue and serum levels of SAA are
      associated with insulin resistance. SAA has been described as a chemoattractant
      for inflammatory cells and adipose tissue from obese individuals contains
      increased numbers of macrophages. However, whether adipose tissue-derived SAA can
      have a direct impact on macrophage infiltration in adipose tissue or the
      development of insulin resistance is unknown. The aim of this study was to
      investigate the effects of adipose tissue-derived SAA1 on the development of
      insulin resistance and obesity-related inflammation. We have previously
      established a transgenic mouse model expressing human SAA1 in the adipose tissue.
      For this report, hSAA1(+/-) transgenic mice and wild type mice were fed with a
      high fat diet or normal chow. Effects of hSAA1 on glucose metabolism were
      assessed using an oral glucose tolerance test. Real-time PCR was used to measure
      the mRNA levels of macrophage markers and genes related to insulin sensitivity in
      adipose tissue. Cytokines during inflammation were analyzed using a
      Proinflammatory 7-plex Assay. We found similar insulin and glucose levels in
      hSAA1 mice and wt controls during an oral glucose tolerance test and no decrease
      in mRNA levels of genes related to insulin sensitivity in adipose tissue in
      neither male nor female hSAA1 animals. Furthermore, serum levels of
      proinflammatory cytokines and mRNA levels of macrophage markers in adipose tissue
      were not increased in hSAA1 mice. Hence, in this model we find no evidence that
      adipose tissue-derived hSAA1 influences the development of insulin resistance or
      obesity-related inflammation. 

PMID- 23967286
TI  - Influence of a polyphenol-enriched protein powder on exercise-induced
      inflammation and oxidative stress in athletes: a randomized trial using a
      metabolomics approach.
AB  - OBJECTIVES: Polyphenol supplementation was tested as a countermeasure to
      inflammation and oxidative stress induced by 3-d intensified training. METHODS:
      Water soluble polyphenols from blueberry and green tea extracts were captured
      onto a polyphenol soy protein complex (PSPC). Subjects were recruited, and
      included 38 long-distance runners ages 19-45 years who regularly competed in road
      races. Runners successfully completing orientation and baseline testing (N = 35)
      were randomized to 40 g/d PSPC (N = 17) (2,136 mg/d gallic acid equivalents) or
      placebo (N = 18) for 17 d using double-blinded methods and a parallel group
      design, with a 3-d running period inserted at day 14 (2.5 h/d, 70% VO2max). Blood
      samples were collected pre- and post-14 d supplementation, and immediately and 14
      h after the third day of running in subjects completing all aspects of the study
      (N = 16 PSPC, N = 15 placebo), and analyzed using a metabolomics platform with GC
      MS and LC-MS. RESULTS: Metabolites characteristic of gut bacteria metabolism of
      polyphenols were increased with PSPC and 3 d running (e.g., hippurate, 4
      hydroxyhippurate, 4-methylcatechol sulfate, 1.8-, 1.9-, 2.5-fold, respectively,
      P<0.05), an effect which persisted for 14-h post-exercise. Fatty acid oxidation
      and ketogenesis were induced by exercise in both groups, with more ketones at 14
      h post-exercise in PSPC (3-hydroxybutyrate, 1.8-fold, P<0.05). Established
      biomarkers for inflammation (CRP, cytokines) and oxidative stress (protein
      carbonyls) did not differ between groups. CONCLUSIONS: PSPC supplementation over
      a 17-d period did not alter established biomarkers for inflammation and oxidative
      stress but was linked to an enhanced gut-derived phenolic signature and
      ketogenesis in runners during recovery from 3-d heavy exertion. TRIAL
      REGISTRATION: ClinicalTrials.gov, U.S. National Institutes of Health, identifier:
      NCT01775384.

PMID- 23967287
TI  - Protective efficacy and immunogenicity of a combinatory DNA vaccine against
      Influenza A Virus and the Respiratory Syncytial Virus.
AB  - The Respiratory Syncytial Virus (RSV) and Influenza A Virus (IAV) are both two
      major causative agents of severe respiratory tract infections in humans leading
      to hospitalization and thousands of deaths each year. In this study, we evaluated
      the immunogenicity and efficacy of a combinatory DNA vaccine in comparison to the
      single component vaccines against both diseases in a mouse model. Intramuscular
      electroporation with plasmids expressing the hemagglutinin (HA) of IAV and the F
      protein of RSV induced strong humoral immune responses regardless if they were
      delivered in combination or alone. In consequence, high neutralizing antibody
      titers were detected, which conferred protection against a lethal challenge with
      IAV. Furthermore, the viral load in the lungs after a RSV infection could be
      dramatically reduced in vaccinated mice. Concurrently, substantial amounts of
      antigen-specific, polyfunctional CD8+ T-cells were measured after vaccination.
      Interestingly, the cellular response to the hemagglutinin was significantly
      reduced in the presence of the RSV-F encoding plasmid, but not vice versa.
      Although these results indicate a suppressive effect of the RSV-F protein, the
      protective efficacy of the combinatory vaccine was comparable to the efficacy of
      both single-component vaccines. In conclusion, the novel combinatory vaccine
      against RSV and IAV may have great potential to reduce the rate of severe
      respiratory tract infections in humans without increasing the number of necessary
      vaccinations.

PMID- 23967288
TI  - Muscular anatomy of the Podocoryna carnea hydrorhiza.
AB  - The muscular anatomy of the athecate hydroid Podocoryna carnea hydrorhiza is
      elucidated. The polyp-stolon junction is characterized by an opening, here called
      the chloe, in the otherwise continuous hydrorhizal perisarc. The chloe is
      elliptical when the polyp first arises, but takes on a more complex outline as
      multiple stolons anastomose to communicate with that polyp. Surrounding the polyp
      base are spots, here called anchors, which autofluoresce at the same wavelengths
      as perisarc and which, like perisarc, contain chitin as assessed by Calcofluor
      White, Congo Red and wheat germ agglutinin staining. Anchors remain after living
      tissues are digested using KOH. Collagen IV staining indicates that the mesoglea
      is pegged to the anchors and rhodamine phallodin staining detects cytoskeletal F
      actin fibers of the basal epidermis surrounding the anchors. Longitudinal muscle
      fibers of the polyp broaden at the polyp base and are inserted into the mesoglea
      of the underlying stolon, but were neither observed to extend along the stolonal
      axis nor to attach to the anchors. Circular muscular fibers of the polyp extend
      into stolons as a dense collection of strands running along the proximal-distal
      axis of the stolon. These gastrodermal axial muscular fibers extend to the stolon
      tip. Epidermal cells at the stolon tip and the polyp bud display a regular apical
      latticework of F-actin staining. A similar meshwork of F-actin staining was found
      in the extreme basal epidermis of all stolons. Immunohistochemical staining for
      tubulin revealed nerves at stolon tips, but at no other hydrorhizal locations.
      These studies bear on the mechanisms by which the stolon tip and polyp bud
      pulsate, the manner in which the stolon lumen closes, and on the developmental
      origin of the basal epidermis of the hydrorhiza. 

PMID- 23967289
TI  - Metagenomic detection of viruses in aerosol samples from workers in animal
      slaughterhouses.
AB  - Published studies have shown that workers in animal slaughterhouses are at a
      higher risk of lung cancers as compared to the general population. No specific
      causal agents have been identified, and exposures to several chemicals have been
      examined and found to be unrelated. Evidence suggests a biological aetiology as
      the risk is highest for workers who are exposed to live animals or to biological
      material containing animal faeces, urine or blood. To investigate possible
      biological exposures in animal slaughterhouses, we used a metagenomic approach to
      characterise the profile of organisms present within an aerosol sample. An
      assessment of aerosol exposures for individual workers was achieved by the
      collection of personal samples that represent the inhalable fraction of
      dust/bioaerosol in workplace air in both cattle and sheep slaughterhouses. Two
      sets of nine personal aerosol samples were pooled for the cattle processing and
      sheep processing areas respectively, with a total of 332,677,346 sequence reads
      and 250,144,492 sequence reads of 85 bp in length produced for each. Eukaryotic
      genome sequence was found in both sampling locations, and bovine, ovine and human
      sequences were common. Sequences from WU polyomavirus and human papillomavirus
      120 were detected in the metagenomic dataset from the cattle processing area, and
      these sequences were confirmed as being present in the original personal aerosol
      samples. This study presents the first metagenomic description of personal
      aerosol exposure and this methodology could be applied to a variety of
      environments. Also, the detection of two candidate viruses warrants further
      investigation in the setting of occupational exposures in animal slaughterhouses.

PMID- 23967290
TI  - The influence of environmental, biotic and spatial factors on diatom
      metacommunity structure in Swedish headwater streams.
AB  - Stream assemblages are structured by a combination of local (environmental
      filtering and biotic interactions) and regional factors (e.g., dispersal related
      processes). The relative importance of environmental and spatial (i.e., regional)
      factors structuring stream assemblages has been frequently assessed in previous
      large-scale studies, but biotic predictors (potentially reflecting local biotic
      interactions) have rarely been included. Diatoms may be useful for studying the
      effect of trophic interactions on community structure since: (1) a majority of
      experimental studies shows significant grazing effects on diatom species
      composition, and (2) assemblages can be divided into guilds that have different
      susceptibility to grazing. We used a dataset from boreal headwater streams in
      south-central Sweden (covering a spatial extent of ~14000 km(2)), which included
      information about diatom taxonomic composition, abundance of invertebrate grazers
      (biotic factor), environmental (physicochemical) and spatial factors (obtained
      through spatial eigenfunction analyses). We assessed the relative importance of
      environmental, biotic, and spatial factors structuring diatom assemblages, and
      performed separate analyses on different diatom guilds. Our results showed that
      the diatom assemblages were mainly structured by environmental factors. However,
      unique spatial and biological gradients, specific to different guilds and
      unrelated to each other, were also evident. We conclude that biological
      predictors, in combination with environmental and spatial variables, can reveal a
      more complete picture of the local vs. regional control of species assemblages in
      lotic environments. Biotic factors should therefore not be overlooked in applied
      research since they can capture additional local control and therefore increase
      accuracy and performance of predictive models. The inclusion of biotic predictors
      did, however, not significantly influence the unique fraction explained by
      spatial factors, which suggests low bias in previous assessments of unique
      regional control of stream assemblages. 

PMID- 23967291
TI  - DNA ligase IV and artemis act cooperatively to suppress homologous recombination
      in human cells: implications for DNA double-strand break repair.
AB  - Nonhomologous end-joining (NHEJ) and homologous recombination (HR) are two major
      pathways for repairing DNA double-strand breaks (DSBs); however, their respective
      roles in human somatic cells remain to be elucidated. Here we show using a series
      of human gene-knockout cell lines that NHEJ repairs nearly all of the
      topoisomerase II- and low-dose radiation-induced DNA damage, while it negatively
      affects survival of cells harbouring replication-associated DSBs. Intriguingly,
      we find that loss of DNA ligase IV, a critical NHEJ ligase, and Artemis, an NHEJ
      factor with endonuclease activity, independently contribute to increased
      resistance to replication-associated DSBs. We also show that loss of Artemis
      alleviates hypersensitivity of DNA ligase IV-null cells to low-dose radiation-
      and topoisomerase II-induced DSBs. Finally, we demonstrate that Artemis-null
      human cells display increased gene-targeting efficiencies, particularly in the
      absence of DNA ligase IV. Collectively, these data suggest that DNA ligase IV and
      Artemis act cooperatively to promote NHEJ, thereby suppressing HR. Our results
      point to the possibility that HR can only operate on accidental DSBs when NHEJ is
      missing or abortive, and Artemis may be involved in pathway switching from
      incomplete NHEJ to HR. 

PMID- 23967292
TI  - HIV care in the Swedish-Danish HIV cohort 1995-2010, closing the gaps.
AB  - BACKGROUND: Successful treatment reduces morbidity, mortality and transmission of
      HIV. We evaluated trends in the treatment status of HIV infected individuals
      enrolled in care in Sweden and Denmark during the years 1995-2010. Our aim was to
      assess the proportion of HIV-infected individuals who received services along the
      continuum of care in Denmark in 2010, and to discuss the findings in relation to
      the organization of the health care system. METHODS: We analyzed CD4 counts and
      viral loads (VL) among all HIV patients enrolled in the cohort. For each month of
      the study period we estimated the proportions of patients who 1) had initiated
      highly active antiretroviral treatment (HAART) and had VL<500 copies/mL, 2) were
      not eligible for HAART, 3) had initiated HAART but had VL>=500 copies/mL, 4) were
      eligible for, but had not initiated HAART and 5) had initiated HAART but no VL
      monitoring for >13 months or 6) no HAART or monitoring of CD4 for >13 months.
      Patients fulfilling criteria 1 or 2 were considered successfully managed.
      RESULTS: The proportion of successfully managed patients continued to increase
      throughout the study period and reached 83% in 2010, 92% of Swedish/Danish men
      who have sex with men and heterosexual patients, but only 74% of immigrants and
      78% of injection drug users were successfully managed due to higher rates of
      inadequate monitoring in the latter two groups. In 2010, 70% of all individuals
      diagnosed with HIV in Denmark were virally suppressed. CONCLUSION: In a public
      health care system with free access to specialized care, successful management of
      the majority of HIV patients is achievable. Interventions tailored to retain
      immigrants and injection drug users in care are needed to further reduce the
      proportion of sub-optimally treated HIV patients.

PMID- 23967293
TI  - An exploration of heat tolerance in mice utilizing mRNA and microRNA expression
      analysis.
AB  - BACKGROUND: Individuals who rapidly develop hyperthermia during heat exposure
      (heat-intolerant) are vulnerable to heat associated illness and injury. We
      recently reported that heat intolerant mice exhibit complex alterations in stress
      proteins in response to heat exposure. In the present study, we further explored
      the role of genes and molecular networks associated with heat tolerance in mice.
      METHODOLOGY: Heat-induced physiological and biochemical changes were assessed to
      determine heat tolerance levels in mice. We performed RNA and microRNA expression
      profiling on mouse gastrocnemius muscle tissue samples to determine novel
      biological pathways associated with heat tolerance. PRINCIPAL FINDINGS: Mice (n =
      18) were assigned to heat-tolerant (TOL) and heat-intolerant (INT) groups based
      on peak core temperatures during heat exposures. This was followed by biochemical
      assessments (Hsp40, Hsp72, Hsp90 and Hsf1 protein levels). Microarray analysis
      identified a total of 3,081 mRNA transcripts that were significantly misregulated
      in INT compared to TOL mice (p<0.05). Among them, Hspa1a, Dnajb1 and Hspb7 were
      differentially expressed by more than two-fold under these conditions.
      Furthermore, we identified 61 distinct microRNA (miRNA) sequences significantly
      associated with TOL compared to INT mice; eight miRNAs corresponded to target
      sites in seven genes identified as being associated with heat tolerance pathways
      (Hspa1a, Dnajb1, Dnajb4, Dnajb6, Hspa2, Hspb3 and Hspb7). CONCLUSIONS: The
      combination of mRNA and miRNA data from the skeletal muscle of adult mice
      following heat stress provides new insights into the pathophysiology of
      thermoregulatory disturbances of heat intolerance.

PMID- 23967294
TI  - Hazard analysis of critical control points assessment as a tool to respond to
      emerging infectious disease outbreaks.
AB  - Highly pathogenic avian influenza virus (HPAI) strain H5N1 has had direct and
      indirect economic impacts arising from direct mortality and control programmes in
      over 50 countries reporting poultry outbreaks. HPAI H5N1 is now reported as the
      most widespread and expensive zoonotic disease recorded and continues to pose a
      global health threat. The aim of this research was to assess the potential of
      utilising Hazard Analysis of Critical Control Points (HACCP) assessments in
      providing a framework for a rapid response to emerging infectious disease
      outbreaks. This novel approach applies a scientific process, widely used in food
      production systems, to assess risks related to a specific emerging health threat
      within a known zoonotic disease hotspot. We conducted a HACCP assessment for HPAI
      viruses within Vietnam's domestic poultry trade and relate our findings to the
      existing literature. Our HACCP assessment identified poultry flock isolation,
      transportation, slaughter, preparation and consumption as critical control points
      for Vietnam's domestic poultry trade. Introduction of the preventative measures
      highlighted through this HACCP evaluation would reduce the risks posed by HPAI
      viruses and pressure on the national economy. We conclude that this HACCP
      assessment provides compelling evidence for the future potential that HACCP
      analyses could play in initiating a rapid response to emerging infectious
      diseases. 

PMID- 23967295
TI  - Absence of functional leptin receptor isoforms in the POUND (Lepr(db/lb)) mouse
      is associated with muscle atrophy and altered myoblast proliferation and
      differentiation.
AB  - OBJECTIVE: Leptin receptors are abundant in human skeletal muscle, but the role
      of leptin in muscle growth, development and aging is not well understood. Here we
      utilized a novel mouse model lacking all functional leptin receptor isoforms
      (POUND mouse, Lepr(db/lb)) to determine the role of leptin in skeletal muscle.
      METHODS AND FINDINGS: Skeletal muscle mass and fiber diameters were examined in
      POUND mice, and primary myoblast cultures were used to determine the effects of
      altered leptin signaling on myoblast proliferation and differentiation. ELISA
      assays, integrated pathway analysis of mRNA microarrays, and reverse phase
      protein analysis were performed to identify signaling pathways impacted by leptin
      receptor deficiency. Results show that skeletal muscle mass and fiber diameter
      are reduced 30-40% in POUND mice relative to wild-type controls. Primary myoblast
      cultures demonstrate decreased proliferation and decreased expression of both
      MyoD and myogenin in POUND mice compared to normal mice. Leptin treatment
      increased proliferation in primary myoblasts from muscles of both adult (12
      months) and aged (24 months) wild-type mice, and leptin increased expression of
      MyoD and myogenin in aged primary myoblasts. ELISA assays and protein arrays
      revealed altered expression of molecules associated with the IGF-1/Akt and
      MAPK/MEK signaling pathways in muscle from the hindlimbs of mice lacking
      functional leptin receptors. CONCLUSION: These data support the hypothesis that
      the adipokine leptin is a key factor important for the regulation of skeletal
      muscle mass, and that leptin can act directly on its receptors in peripheral
      tissues to regulate cell proliferation and differentiation.

PMID- 23967296
TI  - Pituitary adenylate cyclase-activating polypeptide 6-38 blocks cocaine- and
      amphetamine-regulated transcript Peptide-induced hypophagia in rats.
AB  - Cocaine- and amphetamine-regulated transcript peptides (CARTp) suppress
      nutritional intake after administration into the fourth intracerebral ventricle.
      Recent in vitro studies have shown that PACAP 6-38, a pituitary adenylate cyclase
      activating polypeptide (PACAP) fragment, could act as a competitive antagonist
      against CARTp 55-102 on a common CARTp-sensitive receptor structure. Here, we
      show for the first time in vivo that the reduction in solid food intake induced
      by exogenous CARTp 55-102 (0.3 nmol: 1.5 ug) administered fourth i.c.v. is
      blocked by pretreatment with PACAP 6-38 (3 nmol). The PACAP 6-38 fragment had no
      effect by itself either when given into the fourth ventricle or subcutaneously.
      Although effective to block the CARTp-effect on feeding and short-term body
      weight, PACAP 6-38 failed to attenuate CARTp-associated gross motor behavioral
      changes suggesting at least two CARTp-sensitive receptor subtypes. In conclusion,
      PACAP 6-38 acts as a functional CARTp antagonist in vivo and blocks its effects
      on feeding and short term weight gain. 

PMID- 23967297
TI  - Age-related modulation of the effects of obesity on gene expression profiles of
      mouse bone marrow and epididymal adipocytes.
AB  - This study aimed to characterize and compare the effects of obesity on gene
      expression profiles in two distinct adipose depots, epididymal and bone marrow,
      at two different ages in mice. Alterations in gene expression were analyzed in
      adipocytes isolated from diet-induced obese (DIO) C57BL/6J male mice at 6 and 14
      months of age and from leptin deficient mice (ob/ob) at 6 months of age using
      microarrays. DIO affected gene expression in both depots at 6 and 14 months, but
      more genes were altered in epididymal than bone marrow adipocytes at each age and
      younger mice displayed more changes than older animals. In epididymal adipocytes
      a total of 2789 (9.6%) genes were differentially expressed at 6-months with DIO,
      whereas 952 (3.3%) were affected at 14-months. In bone marrow adipocytes, 347
      (1.2%) genes were differentially expressed at 6-months with DIO, whereas only 189
      (0.66%) were changed at 14-months. 133 genes were altered by DIO in both fat
      depots at 6-months, and 37 genes at 14-months. Only four genes were altered in
      both depots at both ages with DIO. Bone marrow adipocytes are less responsive to
      DIO than epididymal adipocytes and the response of both depots to DIO declines
      with age. This loss of responsiveness with age is likely due to age-associated
      changes in expression of genes related to adipogenesis, inflammation and
      mitochondrial function that are similar to and obscure the changes commonly
      associated with DIO. Patterns of gene expression were generally similar in
      epididymal adipocytes from ob/ob and DIO mice; however, several genes were
      differentially expressed in bone marrow adipocytes from ob/ob and DIO mice,
      perhaps reflecting the importance of leptin signaling for bone metabolism. In
      conclusion, obesity affects age-associated alterations in gene expression in both
      epididymal and bone marrow adipocytes regardless of diet or genetic background. 

PMID- 23967298
TI  - Conifer stored resources and resistance to a fungus associated with the spruce
      bark beetle Ips typographus.
AB  - Bark beetles and associated fungi are among the greatest natural threats to
      conifers worldwide. Conifers have potent defenses, but resistance to beetles and
      fungal pathogens may be reduced if tree stored resources are consumed by fungi
      rather than used for tree defense. Here, we assessed the relationship between
      tree stored resources and resistance to Ceratocystis polonica, a phytopathogenic
      fungus vectored by the spruce bark beetle Ips typographus. We measured phloem and
      sapwood nitrogen, non-structural carbohydrates (NSC), and lipids before and after
      trees were attacked by I. typographus (vectoring C. polonica) or artificially
      inoculated with C. polonica alone. Tree resistance was assessed by measuring
      phloem lesions and the proportion of necrotic phloem around the tree's
      circumference following attack or inoculation. While initial resource
      concentrations were unrelated to tree resistance to C. polonica, over time,
      phloem NSC and sapwood lipids declined in the trees inoculated with C. polonica.
      Greater resource declines correlated with less resistant trees (trees with larger
      lesions or more necrotic phloem), suggesting that resource depletion may be
      caused by fungal consumption rather than tree resistance. Ips typographus may
      then benefit indirectly from reduced tree defenses caused by fungal resource
      uptake. Our research on tree stored resources represents a novel way of
      understanding bark beetle-fungal-conifer interactions. 

PMID- 23967299
TI  - Endoglin-mediated suppression of prostate cancer invasion is regulated by activin
      and bone morphogenetic protein type II receptors.
AB  - Mortality from prostate cancer (PCa) is due to the formation of metastatic
      disease. Understanding how that process is regulated is therefore critical. We
      previously demonstrated that endoglin, a type III transforming growth factor beta
      (TGFbeta) superfamily receptor, suppresses human PCa cell invasion and
      metastasis. Endoglin-mediated suppression of invasion was also shown by us to be
      dependent upon the type I TGFbeta receptor, activin receptor-like kinase 2
      (ALK2), and the downstream effector, Smad1. In this study we demonstrate for the
      first time that two type II TGFbeta receptors are required for endoglin-mediated
      suppression of invasion: activin A receptor type IIA (ActRIIA) and bone
      morphogenetic protein receptor type II (BMPRII). Downstream signaling through
      these receptors is predominantly mediated by Smad1. ActRIIA stimulates Smad1
      activation in a kinase-dependent manner, and this is required for suppression of
      invasion. In contrast BMPRII regulates Smad1 in a biphasic manner, promoting
      Smad1 signaling through its kinase domain but suppressing it through its
      cytoplasmic tail. BMPRII's Smad1-regulatory effects are dependent upon its
      expression level. Further, its ability to suppress invasion is independent of
      either kinase function or tail domain. We demonstrate that ActRIIA and BMPRII
      physically interact, and that each also interacts with endoglin. The current
      findings demonstrate that both BMPRII and ActRIIA are necessary for endoglin
      mediated suppression of human PCa cell invasion, that they have differential
      effects on Smad1 signaling, that they make separate contributions to regulation
      of invasion, and that they functionally and physically interact. 

PMID- 23967300
TI  - Novel synthetic monoketone transmute radiation-triggered NFkappaB-dependent
      TNFalpha cross-signaling feedback maintained NFkappaB and favors neuroblastoma
      regression.
AB  - Recently, we demonstrated that radiation (IR) instigates the occurrence of a
      NFkappaB-TNFalpha feedback cycle which sustains persistent NFkappaB activation in
      neuroblastoma (NB) cells and favors survival advantage and clonal expansion.
      Further, we reported that curcumin targets IR-induced survival signaling and
      NFkappaB dependent hTERT mediated clonal expansion in human NB cells. Herein, we
      investigated the efficacy of a novel synthetic monoketone, EF24, a curcumin
      analog in inhibiting persistent NFkappaB activation by disrupting the IR-induced
      NFkappaB-TNFalpha-NFkappaB feedback signaling in NB and subsequent mitigation of
      survival advantage and clonal expansion. EF24 profoundly suppressed the IR
      induced NFkappaB-DNA binding activity/promoter activation and, maintained the
      NFkappaB repression by deterring NFkappaB-dependent TNFalpha
      transactivation/intercellular secretion in genetically varied human NB (SH-SY5Y,
      IMR-32, SK-PN-DW, MC-IXC and SK-N-MC) cell types. Further, EF24 completely
      suppressed IR-induced NFkappaB-TNFalpha cross-signaling dependent
      transactivation/translation of pro-survival IAP1, IAP2 and Survivin and
      subsequent cell survival. In corroboration, EF24 treatment maximally blocked IR
      induced NFkappaB dependent hTERT transactivation/promoter activation, telomerase
      activation and consequent clonal expansion. EF24 displayed significant regulation
      of IR-induced feedback dependent NFkappaB and NFkappaB mediated survival
      signaling and complete regression of NB xenograft. Together, the results
      demonstrate for the first time that, novel synthetic monoketone EF24 potentiates
      radiotherapy and mitigates NB progression by selectively targeting IR-triggered
      NFkappaB-dependent TNFalpha-NFkappaB cross-signaling maintained NFkappaB mediated
      survival advantage and clonal expansion. 

PMID- 23967301
TI  - Does coral disease affect symbiodinium? Investigating the impacts of growth
      anomaly on symbiont photophysiology.
AB  - Growth anomaly (GA) is a commonly observed coral disease that impairs biological
      functions of the affected tissue. GA is prevalent at Wai 'opae tide pools,
      southeast Hawai 'i Island. Here two distinct forms of this disease, Type A and
      Type B, affect the coral, Montiporacapitata. While the effects of GA on biology
      and ecology of the coral host are beginning to be understood, the impact of this
      disease on the photophysiology of the dinoflagellate symbiont, Symbiodinium spp.,
      has not been investigated. The GA clearly alters coral tissue structure and
      skeletal morphology and density. These tissue and skeletal changes are likely to
      modify not only the light micro-environment of the coral tissue, which has a
      direct impact on the photosynthetic potential of Symbiodinium spp., but also the
      physiological interactions within the symbiosis. This study utilized Pulse
      amplitude modulation fluorometry (PAM) to characterize the photophysiology of
      healthy and GA-affected M. capitata tissue. Overall, endosymbionts within GA
      affected tissue exhibit reduced photochemical efficiency. Values of both Fv/Fm
      and DeltaF/ Fm' were significantly lower (p<0.01) in GA tissue compared to
      healthy and unaffected tissues. Tracking the photophysiology of symbionts over a
      diurnal time period enabled a comparison of symbiont responses to
      photosynthetically available radiation (PAR) among tissue conditions. Symbionts
      within GA tissue exhibited the lowest values of DeltaF/Fm' as well as the highest
      pressure over photosystem II (p<0.01). This study provides evidence that the
      symbionts within GA-affected tissue are photochemically compromised compared to
      those residing in healthy tissue. 

PMID- 23967303
TI  - Seagrass restoration enhances "blue carbon" sequestration in coastal waters.
AB  - Seagrass meadows are highly productive habitats that provide important ecosystem
      services in the coastal zone, including carbon and nutrient sequestration.
      Organic carbon in seagrass sediment, known as "blue carbon," accumulates from
      both in situ production and sedimentation of particulate carbon from the water
      column. Using a large-scale restoration (>1700 ha) in the Virginia coastal bays
      as a model system, we evaluated the role of seagrass, Zosteramarina, restoration
      in carbon storage in sediments of shallow coastal ecosystems. Sediments of
      replicate seagrass meadows representing different age treatments (as time since
      seeding: 0, 4, and 10 years), were analyzed for % carbon, % nitrogen, bulk
      density, organic matter content, and 210Pb for dating at 1-cm increments to a
      depth of 10 cm. Sediment nutrient and organic content, and carbon accumulation
      rates were higher in 10-year seagrass meadows relative to 4-year and bare
      sediment. These differences were consistent with higher shoot density in the
      older meadow. Carbon accumulation rates determined for the 10-year restored
      seagrass meadows were 36.68 g C m-2 yr-1. Within 12 years of seeding, the
      restored seagrass meadows are expected to accumulate carbon at a rate that is
      comparable to measured ranges in natural seagrass meadows. This the first study
      to provide evidence of the potential of seagrass habitat restoration to enhance
      carbon sequestration in the coastal zone.

PMID- 23967302
TI  - Expression of galectin-7 is induced in breast cancer cells by mutant p53.
AB  - Galectin-7 was initially described as a marker of epithelial differentiation
      expressed in the stratified epithelium of various tissues. Like other members of
      the galectin family, its expression level is often significantly altered in
      cancer cells. In breast cancer, its expression is significantly augmented in
      aggressive molecular subtypes, most notably in estrogen receptor-negative tumors
      and in cell lines with a basal-like phenotype. Studies using experimental mouse
      models have further shown high expression of galectin-7 was sufficient to
      increase the metastatic behavior of poorly metastatic breast cancer cells,
      rendering them more resistant to apoptosis. This expression pattern in breast
      cancer cells is unexpected because galectin-7 was originally identified as a p53
      induced gene. To address this paradox, we have examined the molecular mechanisms
      regulating galectin-7 in breast cancer cells. Our results showed that
      transfection of breast cancer cells with expression vectors encoding mutant p53
      was sufficient to induce galectin-7 at both mRNA and protein levels. Doxorubicin
      treatment of breast cancer cells harboring a mutant p53 also induced galectin-7.
      This induction was specific since knockdown of endogenous mutant p53 inhibited
      doxorubicin-induced galectin-7 expression. The p53-induced galectin-7 expression
      in breast cancer cells correlated with increased NF-kappaB activity and was
      inhibited by NF-kappaB inhibitors, indicating that the ability of mutant p53 to
      induce galectin-7 was dependent on NF-kappaB activity. The implication of NF
      kappaB was further supported by data showing that NF-kappaB bound to the
      endogenous galectin-7 promoter and that TNFalpha-induced galectin-7 expression
      was abolished by NF-kappaB inhibitors. Taken together, our data provide an
      explanation to the observed high galectin-7 expression levels in cancer cells and
      suggest that galectin-7 could be part of a common pathway used by mutant p53 to
      promote cancer progression. 

PMID- 23967304
TI  - The effects of temperature and body mass on jump performance of the locust
      Locusta migratoria.
AB  - Locusts jump by rapidly releasing energy from cuticular springs built into the
      hind femur that deform when the femur muscle contracts. This study is the first
      to examine the effect of temperature on jump energy at each life stage of any
      orthopteran. Ballistics and high-speed cinematography were used to quantify the
      energy, distance, and take-off angle of the jump at 15, 25, and 35 degrees C in
      the locust Locusta migratoria. Allometric analysis across the five juvenile
      stages at 35 degrees C reveals that jump distance (D; m) scales with body mass
      (M; g) according to the power equation D = 0.35M (0.17+/-0.08 (95% CI)), jump
      take-off angle (A; degrees) scales as A = 52.5M (0.00+/-0.06), and jump energy
      (E; mJ per jump) scales as E = 1.91M (1.14+/-0.09). Temperature has no
      significant effect on the exponent of these relationships, and only a modest
      effect on the elevation, with an overall Q10 of 1.08 for jump distance and 1.09
      for jump energy. On average, adults jump 87% farther and with 74% more energy
      than predicted based on juvenile scaling data. The positive allometric scaling of
      jump distance and jump energy across the juvenile life stages is likely
      facilitated by the concomitant relative increase in the total length (L f+t; mm)
      of the femur and tibia of the hind leg, L f+t = 34.9M (0.37+/-0.02). The weak
      temperature-dependence of jump performance can be traced to the maximum tension
      of the hind femur muscle and the energy storage capacity of the femur's cuticular
      springs. The disproportionately greater jump energy and jump distance of adults
      is associated with relatively longer (12%) legs and a relatively larger (11%)
      femur muscle cross-sectional area, which could allow more strain loading into the
      femur's cuticular springs. Augmented jump performance in volant adult locusts
      achieves the take-off velocity required to initiate flight. 

PMID- 23967305
TI  - Structural basis for the interaction of the adaptor protein grb14 with activated
      ras.
AB  - Grb14, a member of the Grb7-10-14 family of cytoplasmic adaptor proteins, is a
      tissue-specific negative regulator of insulin signaling. Grb7-10-14 contain
      several signaling modules, including a Ras-associating (RA) domain, a pleckstrin
      homology (PH) domain, a family-specific BPS (between PH and SH2) region, and a C
      terminal Src-homology-2 (SH2) domain. We showed previously that the RA and PH
      domains, along with the BPS region and SH2 domain, are necessary for
      downregulation of insulin signaling. Here, we report the crystal structure at 2.4
      A resolution of the Grb14 RA and PH domains in complex with GTP-loaded H-Ras
      (G12V). The structure reveals that the Grb14 RA and PH domains form an integrated
      structural unit capable of binding simultaneously to small GTPases and
      phosphoinositide lipids. The overall mode of binding of the Grb14 RA domain to
      activated H-Ras is similar to that of the RA domains of RalGDS and Raf1 but with
      important distinctions. The integrated RA-PH structural unit in Grb7-10-14 is
      also found in a second adaptor family that includes Rap1-interacting adaptor
      molecule (RIAM) and lamellipodin, proteins involved in actin-cytoskeleton
      rearrangement. The structure of Grb14 RA-PH in complex with H-Ras represents the
      first detailed molecular characterization of tandem RA-PH domains bound to a
      small GTPase and provides insights into the molecular basis for specificity. 

PMID- 23967306
TI  - Modeling of non-steroidal anti-inflammatory drug effect within signaling pathways
      and miRNA-regulation pathways.
AB  - To date, it is widely recognized that Non-Steroidal Anti-Inflammatory Drugs
      (NSAIDs) can exert considerable anti-tumor effects regarding many types of
      cancers. The prolonged use of NSAIDs is highly associated with diverse side
      effects. Therefore, tailoring down the NSAID application onto individual patients
      has become a necessary and relevant step towards personalized medicine. This
      study conducts the systemsbiological approach to construct a molecular model
      (NSAID model) containing a cyclooxygenase (COX)-pathway and its related signaling
      pathways. Four cancer hallmarks are integrated into the model to reflect
      different developmental aspects of tumorigenesis. In addition, a Flux-Comparative
      Analysis (FCA) based on Petri net is developed to transfer the dynamic properties
      (including drug responsiveness) of individual cellular system into the model. The
      gene expression profiles of different tumor-types with available drug-response
      information are applied to validate the predictive ability of the NSAID model.
      Moreover, two therapeutic developmental strategies, synthetic lethality and
      microRNA (miRNA) biomarker discovery, are investigated based on the COX-pathway.
      In conclusion, the result of this study demonstrates that the NSAID model
      involving gene expression, gene regulation, signal transduction, protein
      interaction and other cellular processes, is able to predict the individual
      cellular responses for different therapeutic interventions (such as NS-398 and
      COX-2 specific siRNA inhibition). This strongly indicates that this type of model
      is able to reflect the physiological, developmental and pathological processes of
      an individual. The approach of miRNA biomarker discovery is demonstrated for
      identifying miRNAs with oncogenic and tumor suppressive functions for individual
      cell lines of breast-, colon- and lung-tumor. The achieved results are in line
      with different independent studies that investigated miRNA biomarker related to
      diagnostics of cancer treatments, therefore it might shed light on the
      development of biomarker discovery at individual level. Particular results of
      this study might contribute to step further towards personalized medicine with
      the systemsbiological approach. 

PMID- 23967307
TI  - Cis association of galectin-9 with Tim-3 differentially regulates IL-12/IL-23
      expressions in monocytes via TLR signaling.
AB  - Human monocytes/macrophages (M/M(F)) of the innate immunity sense and respond to
      microbial products via specific receptor coupling with stimulatory (such as TLR)
      and inhibitory (such as Tim-3) receptors. Current models imply that Tim-3
      expression on M/M(O) can deliver negative signaling to TLR-mediated IL-12
      expression through trans association with its ligand Galectin-9 (Gal-9) presented
      by other cells. However, Gal-9 is also expressed within M/M(O), and the effect of
      intracellular Gal-9 on Tim-3 activities and inflammatory responses in the same
      M/M(O) remains unknown. In this study, our data suggest that Tim-3 and IL-12/IL
      23 gene transcriptions are regulated by enhanced or silenced Gal-9 expression
      within monocytes through synergizing with TLR signaling. Additionally, TLR
      activation facilitates Gal-9/Tim-3 cis association within the same M/M(O) to
      differentially regulate IL-12/IL-23 expressions through STAT-3 phosphorylation.
      These results reveal a ligand (Gal-9) compartment-dependent regulatory effect on
      receptor (Tim-3) activities and inflammatory responses via TLR pathways--a novel
      mechanism underlying cellular responses to external or internal cues.

PMID- 23967308
TI  - Modulation of oxidative stress by twist oncoproteins.
AB  - Expression of developmental genes Twist1 and Twist2 is reactivated in many human
      tumors. Among their oncogenic activities, induction of epithelial to mesenchymal
      transition is believed to increase cell motility and invasiveness and may be
      related to acquisition of cancer stem cell phenotype. In addition, Twist proteins
      promote malignant conversion by overriding two oncogene-induced failsafe
      programs: senescence and apoptosis. Reactive oxygen species (ROS) are also
      important mediators of apoptosis, senescence and motility and are tightly linked
      to disease, notably to cancer. We report here that Twist factors and ROS are
      functionally linked. In wild type cells both Twist1 and Twist2 exhibit
      antioxidant properties. We show that Twist-driven modulation of oncogene-induced
      apoptosis is linked to its effects on oxidative stress. Finally, we identify
      several targets that mediate Twist antioxidant activity. These findings unveil a
      new function of Twist factors that could be important in explaining their
      pleiotropic role during carcinogenesis. 

PMID- 23967309
TI  - Pre-synaptic release deficits in a DYT1 dystonia mouse model.
AB  - DYT1 early-onset generalized torsion dystonia (DYT1 dystonia) is an inherited
      movement disorder caused by mutations in one allele of DYT1 (TOR1A), coding for
      torsinA. The most common mutation is a trinucleotide deletion (DeltaGAG), which
      causes a deletion of a glutamic acid residue (DeltaE) in the C-terminal region of
      torsinA. Although recent studies using cultured cells suggest that torsinA
      contributes to protein processing in the secretory pathway, endocytosis, and the
      stability of synaptic proteins, the nature of how this mutation affects synaptic
      transmission remains unclear. We previously reported that theta-burst-induced
      long-term potentiation (LTP) in the CA1 region of the hippocampal slice is not
      altered in Dyt1 DeltaGAG heterozygous knock-in (KI) mice. Here, we examined short
      term synaptic plasticity and synaptic transmission in the hippocampal slices.
      Field recordings in the hippocampal Schaffer collaterals (SC) pathway revealed
      significantly enhanced paired pulse ratios (PPRs) in Dyt1 DeltaGAG heterozygous
      KI mice, suggesting an impaired synaptic vesicle release. Whole-cell recordings
      from the CA1 neurons showed that Dyt1 DeltaGAG heterozygous KI mice exhibited
      normal miniature excitatory post-synaptic currents (mEPSC), suggesting that
      action-potential independent spontaneous pre-synaptic release was normal. On the
      other hand, there was a significant decrease in the frequency, but not amplitude
      or kinetics, of spontaneous excitatory post-synaptic currents (sEPSC) in Dyt1
      DeltaGAG heterozygous KI mice, suggesting that the action-potential dependent pre
      synaptic release was impaired. Moreover, hippocampal torsinA was significantly
      reduced in Dyt1 DeltaGAG heterozygous KI mice. Although the hippocampal slice
      model may not represent the neurons directly associated with dystonic symptoms,
      impaired release of neurotransmitters caused by partial dysfunction of torsinA in
      other brain regions may contribute to the pathophysiology of DYT1 dystonia. 

PMID- 23967310
TI  - SR-BI in bone marrow derived cells protects mice from diet induced coronary
      artery atherosclerosis and myocardial infarction.
AB  - SR-BI deficient mice that are also hypomorphic for apolipoprotein E expression
      develop diet induced occlusive coronary artery atherosclerosis, myocardial
      infarction and early death. To test the role of SR-BI in bone marrow derived
      cells, we used bone marrow transplantation to generate SR-BI-null; apoE
      hypomorphic mice in which SR-BI expression was restored solely in bone marrow
      derived cells. SR-BI-null; apoE-hypomorphic mice were transplanted with SR
      BI(+/+)apoE-hypomorphic, or control, autologous SR-BI-null; apoE-hypomorphic bone
      marrow. Four weeks later, mice were fed a high-fat, high-cholesterol, cholate
      containing diet to induce coronary artery atherosclerosis. Mice transplanted with
      autologous bone marrow developed extensive aortic atherosclerosis and severe
      occlusive coronary artery atherosclerosis after 4 weeks of feeding. This was
      accompanied by myocardial fibrosis and increased heart weights. In contrast,
      restoration of SR-BI expression in bone marrow derived-cells reduced diet induced
      aortic and coronary artery atherosclerosis, myocardial fibrosis and the increase
      in heart weights in SR-BI-null; apoE-hypomorphic mice. Restoration of SR-BI in
      bone marrow derived cells did not, however, affect steady state lipoprotein
      cholesterol levels, but did reduce plasma levels of IL-6. Monocytes from SR-BI
      null mice exhibited a greater capacity to bind to VCAM-1 and ICAM-1 than those
      from SR-BI(+/+) mice. Furthermore, restoration of SR-BI expression in bone marrow
      derived cells attenuated monocyte recruitment into atherosclerotic plaques in
      mice fed high fat, high cholesterol cholate containing diet. These data
      demonstrate directly that SR-BI in bone marrow-derived cells protects against
      both aortic and CA atherosclerosis. 

PMID- 23967311
TI  - Major clades of Australasian Rutoideae (Rutaceae) based on rbcL and atpB
      sequences.
AB  - BACKGROUND: Rutaceae subfamily Rutoideae (46 genera, c. 660 species) is diverse
      in both rainforests and sclerophyll vegetation of Australasia. Australia and New
      Caledonia are centres of endemism with a number of genera and species distributed
      disjunctly between the two regions. Our aim was to generate a high-level
      molecular phylogeny for the Australasian Rutoideae and identify major clades as a
      framework for assessing morphological and biogeographic patterns and taxonomy.
      METHODOLOGY/PRINCIPAL FINDINGS: Phylogenetic analyses were based on chloroplast
      genes, rbcL and atpB, for 108 samples (78 new here), including 38 of 46
      Australasian genera. Results were integrated with those from other molecular
      studies to produce a supertree for Rutaceae worldwide, including 115 of 154
      genera. Australasian clades are poorly matched with existing tribal
      classifications, and genera Philotheca and Boronia are not monophyletic. Major
      sclerophyll lineages in Australia belong to two separate clades, each with an
      early divergence between rainforest and sclerophyll taxa. Dehiscent fruits with
      seeds ejected at maturity (often associated with myrmecochory) are inferred as
      ancestral; derived states include woody capsules with winged seeds, samaras,
      fleshy drupes, and retention and display of seeds in dehisced fruits (the last
      two states adaptations to bird dispersal, with multiple origins among rainforest
      genera). Patterns of relationship and levels of sequence divergence in some taxa,
      mostly species, with bird-dispersed (Acronychia, Sarcomelicope, Halfordia and
      Melicope) or winged (Flindersia) seeds are consistent with recent long-distance
      dispersal between Australia and New Caledonia. Other deeper Australian/New
      Caledonian divergences, some involving ant-dispersed taxa (e.g., Neoschmidia),
      suggest older vicariance. CONCLUSIONS/SIGNIFICANCE: This comprehensive molecular
      phylogeny of the Australasian Rutoideae gives a broad overview of the group's
      evolutionary and biogeographic history. Deficiencies of infrafamilial
      classifications of Rutoideae have long been recognised, and our results provide a
      basis for taxonomic revision and a necessary framework for more focused studies
      of genera and species.

PMID- 23967312
TI  - Evidence against the involvement of chronic cerebrospinal venous abnormalities in
      multiple sclerosis. A case-control study.
AB  - OBJECTIVE: Multiple sclerosis (MS) is a chronic neurodegenerative disease of the
      CNS. Recently a controversial vascular hypothesis for MS, termed chronic
      cerebrospinal venous insufficiency (CCSVI), has been advanced. The objective of
      this study was to evaluate the relative prevalence of the venous abnormalities
      that define CCSVI. METHODS: A case-control study was conducted in which 100 MS
      patients aged between 18-65 y meeting the revised McDonald criteria were randomly
      selected and stratified into one of four MS subtypes: relapsing/remitting,
      secondary progressive, primary progressive and benign. Control subjects (16-70 y)
      with no known history of MS or other neurological condition were matched with the
      MS cases. All cases and controls underwent ultrasound imaging of the veins of the
      neck plus the deep cerebral veins, and magnetic resonance imaging of the neck
      veins and brain. These procedures were performed on each participant on the same
      day. RESULTS: On ultrasound we found no evidence of reflux, stenosis or blockage
      in the internal jugular veins (IJV) or vertebral veins (VV) in any study
      participant. Similarly, there was no evidence of either reflux or cessation of
      flow in the deep cerebral veins in any subject. Flow was detected in the IJV and
      VV in all study participants. Amongst 199 participants there was one MS subject
      who fulfilled the minimum two ultrasound criteria for CCSVI. Using MRI we found
      no significant differences in either the intra- or extra-cranial venous flow
      velocity or venous architecture between cases and controls. CONCLUSION: This case
      control study provides compelling evidence against the involvement of CCSVI in
      multiple sclerosis.

PMID- 23967313
TI  - Heterogeneous nuclear ribonucleoprotein R cooperates with mediator to facilitate
      transcription reinitiation on the c-Fos gene.
AB  - The c-fos gene responds to extracellular stimuli and undergoes robust but
      transient transcriptional activation. Here we show that heterogeneous nuclear
      ribonucleoprotein R (hnRNP R) facilitates transcription reinitiation of the c-fos
      promoter in vitro in cooperation with Mediator. Consistently, hnRNP R interacts
      with the Scaffold components (Mediator, TBP, and TFIIH) as well as TFIIB, which
      recruits RNA polymerase II (Pol II) and TFIIF to Scaffold. The cooperative action
      of hnRNP R and Mediator is diminished by the cyclin-dependent kinase 8 (CDK8)
      module, which is comprised of CDK8, Cyclin C, MED12 and MED13 of the Mediator
      subunits. Interestingly, we find that the length of the G-free cassettes, and
      thereby their transcripts, influences the hnRNP R-mediated facilitation of
      reinitiation. Indeed, indicative of a possible role of the transcript in
      facilitating transcription reinitiation, the RNA transcript produced from the G
      free cassette interacts with hnRNP R through its RNA recognition motifs (RRMs)
      and arginine-glycine-glycine (RGG) domain. Mutational analyses of hnRNP R
      indicate that facilitation of initiation and reinitiation requires distinct
      domains of hnRNP R. Knockdown of hnRNP R in mouse cells compromised rapid
      induction of the c-fos gene but did not affect transcription of constitutive
      genes. Together, these results suggest an important role for hnRNP R in
      regulating robust response of the c-fos gene. 

PMID- 23967314
TI  - Bacterial communities associated with culex mosquito larvae and two emergent
      aquatic plants of bioremediation importance.
AB  - Microbes are important for mosquito nutrition, growth, reproduction and control.
      In this study, we examined bacterial communities associated with larval
      mosquitoes and their habitats. Specifically, we characterized bacterial
      communities associated with late larval instars of the western encephalitis
      mosquito (Culextarsalis), the submerged portions of two emergent macrophytes
      (California bulrush, Schoenoplectuscalifornicus and alkali bulrush,
      Schoenoplectusmaritimus), and the associated water columns to investigate
      potential differential use of resources by mosquitoes in different wetland
      habitats. Using next-generation sequence data from 16S rRNA gene hypervariable
      regions, the alpha diversity of mosquito gut microbial communities did not differ
      between pond mesocosms containing distinct monotypic plants. Proteobacteria,
      dominated by the genus Thorsellia (Enterobacteriaceae), was the most abundant
      phylum recovered from C. tarsalis larvae. Approximately 49% of bacterial OTUs
      found in larval mosquitoes were identical to OTUs recovered from the water column
      and submerged portions of the two bulrushes. Plant and water samples were similar
      to one another, both being dominated by Actinobacteria, Bacteroidetes,
      Cyanobacteria, Proteobacteria and Verrucomicrobia phyla. Overall, the bacterial
      communities within C. tarsalis larvae were conserved and did not change across
      sampling dates and between two distinct plant habitats. Although Thorsellia spp.
      dominated mosquito gut communities, overlap of mosquito gut, plant and water
      column OTUs likely reveal the effects of larval feeding. Future research will
      investigate the role of the key indicator groups of bacteria across the different
      developmental stages of this mosquito species. 

PMID- 23967315
TI  - Slower uncoating is associated with impaired replicative capability of simian
      tropic HIV-1.
AB  - Human immunodeficiency virus type 1 (HIV-1) productively infects only humans and
      chimpanzees, but not Old World monkeys, such as rhesus and cynomolgus (CM)
      monkeys. To establish a monkey model of HIV-1/AIDS, several HIV-1 derivatives
      have been constructed. We previously generated a simian-tropic HIV-1 that
      replicates efficiently in CM cells. This virus encodes a capsid protein (CA) with
      SIVmac239-derived loops between alpha-helices 4 and 5 (L4/5) and between alpha
      helices 6 and 7 (L6/7), along with the entire vif from SIVmac239 (NL
      4/5S6/7SvifS). These SIVmac239-derived sequences were expected to protect the
      virus from HIV-1 restriction factors in monkey cells. However, the replicative
      capability of NL-4/5S6/7SvifS in human cells was severely impaired. By long-term
      cultivation of human CEM-SS cells infected with NL-4/5S6/7SvifS, we succeeded in
      partially rescuing the impaired replicative capability of the virus in human
      cells. This adapted virus encoded a G-to-E substitution at the 116(th) position
      of the CA (NL-4/5SG116E6/7SvifS). In the work described here, we explored the
      mechanism by which the replicative capability of NL-4/5S6/7SvifS was impaired in
      human cells. Quantitative analysis (by real-time PCR) of viral DNA synthesis from
      infected cells revealed that NL-4/5S6/7SvifS had a major defect in nuclear entry.
      Mutations in CA are known to affect viral core stability and result in
      deleterious effects in HIV-1 infection; therefore, we measured the kinetics of
      uncoating of these viruses. The uncoating of NL-4/5S6/7SvifS was significantly
      slower than that of wild type HIV-1 (WT), whereas the uncoating of NL
      4/5SG116E6/7SvifS was similar to that of WT. Our results suggested that the lower
      replicative capability of NL-4/5S6/7SvifS in human cells was, at least in part,
      due to the slower uncoating of this virus. 

PMID- 23967316
TI  - Unique features of two potassium channels, OsKAT2 and OsKAT3, expressed in rice
      guard cells.
AB  - Potassium is the most abundant cation and a myriad of transporters regulate K(+)
      homeostasis in plant. Potassium plays a role as a major osmolyte to regulate
      stomatal movements that control water utility of land plants. Here we report the
      characterization of two inward rectifying shaker-like potassium channels, OsKAT2
      and OsKAT3, expressed in guard cell of rice plants. While OsKAT2 showed typical
      potassium channel activity, like that of Arabidopsis KAT1, OsKAT3 did not despite
      high sequence similarity between the two channel proteins. Interestingly, the two
      potassium channels physically interacted with each other and such interaction
      negatively regulated the OsKAT2 channel activity in CHO cell system. Furthermore,
      deletion of the C-terminal domain recovered the channel activity of OsKAT3,
      suggesting that the C-terminal region was regulatory domain that inhibited
      channel activity. Two homologous channels with antagonistic interaction has not
      been previously reported and presents new information for potassium channel
      regulation in plants, especially in stomatal regulation. 

PMID- 23967317
TI  - Diabetes and pre-diabetes among persons aged 35 to 60 years in eastern Uganda:
      prevalence and associated factors.
AB  - BACKGROUND: Our aim was to estimate the prevalence of abnormal glucose regulation
      (AGR) (i.e. diabetes and pre-diabetes) and its associated factors among people
      aged 35-60 years so as to clarify the relevance of targeted screening in rural
      Africa. METHODS: A population-based survey of 1,497 people (786 women and 711
      men) aged 35-60 years was conducted in a predominantly rural Demographic
      Surveillance Site in eastern Uganda. Participants responded to a lifestyle
      questionnaire, following which their Body Mass Index (BMI) and Blood Pressure
      (BP) were measured. Fasting plasma glucose (FPG) was measured from capillary
      blood using On-Call(r) Plus (Acon) rapid glucose meters, following overnight
      fasting. AGR was defined as FPG >=6.1 mmol L-1 (World Health Organization (WHO)
      criteria or >=5.6 mmol L-1 (American Diabetes Association (ADA) criteria.
      Diabetes was defined as FPG >6.9 mmol L-1, or being on diabetes treatment.
      RESULTS: The mean age of participants was 45 years for men and 44 for women.
      Prevalence of diabetes was 7.4% (95%CI 6.1-8.8), while prevalence of pre-diabetes
      was 8.6% (95%CI 7.3-10.2) using WHO criteria and 20.2% (95%CI 17.5-22.9) with ADA
      criteria. Using WHO cut-offs, the prevalence of AGR was 2 times higher among
      obese persons compared with normal BMI persons (Adjusted Prevalence Rate Ratio
      (APRR) 1.9, 95%CI 1.3-2.8). Occupation as a mechanic, achieving the WHO
      recommended physical activity threshold, and higher dietary diversity were
      associated with lower likelihood of AGR (APRR 0.6, 95%CI 0.4-0.9; APRR 0.6, 95%CI
      0.4-0.8; APRR 0.5, 95%CI 0.3-0.9 respectively). The direct medical cost of
      detecting one person with AGR was two US dollars with ADA and three point seven
      dollars with WHO cut-offs. CONCLUSIONS: There is a high prevalence of AGR among
      people aged 35-60 years in this setting. Screening for high risk persons and
      targeted health education to address obesity, insufficient physical activity and
      non-diverse diets are necessary.

PMID- 23967318
TI  - Combination therapy with atorvastatin and amlodipine suppresses angiotensin II
      induced aortic aneurysm formation.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is a life-threatening vascular
      disease. It is controversial whether statin and calcium channel blockers (CCBs)
      has an inhibitory effect on the expansion of AAA. Some studies reported that CCBs
      have an inhibitory effect on Rho-kinase activity. Rho-kinase plays an important
      role in the pathogenesis of various cardiovascular diseases. However, there is no
      study reporting of the association between Rho-kinase and human AAAs. METHODS AND
      RESULTS: Experimental AAA was induced in Apolipoprotein E-deficient (ApoE(-/-))
      mice infused with angiotensin II (AngII) for 28 days. They were randomly divided
      into the following 5 groups; saline infusion alone (sham), AngII infusion alone,
      AngII infusion plus atorvastatin (10 mg/kg/day), AngII infusion plus amlodipine
      (1 mg/kg/day), and AngII infusion plus combination therapy with atorvastatin (10
      mg/kg/day) and amlodipine (1 mg/kg/day). The combination therapy significantly
      suppressed AngII-induced increase in maximal aortic diameter as compared with
      sham, whereas each monotherapy had no inhibitory effects. The combination therapy
      significantly reduced AngII-induced apoptosis and elastin degradation at the AAA
      lesion, whereas each monotherapy did not. Moreover, Rho-kinase activity, as
      evaluated by the extent of phosphorylation of myosin-binding subunit (a substrate
      of Rho-kinase) and matrix metalloproteinase activity were significantly increased
      in the AngII-induced AAA lesion as compared with sham, both of which were again
      significantly suppressed by the combination therapy. In human aortic samples,
      immunohistochemistory revealed that the activity and expression of Rho-kinase was
      up-regulated in AAA lesion as compared with abdominal aorta from control
      subjects. CONCLUSIONS: Rho-kinase is up-regulated in the aortic wall of human
      AAA. The combination therapy with amlodipine and Atorvastatin, but not each
      monotherapy, suppresses AngII-induced AAA formation in mice in vivo, for which
      Rho-kinase inhibition may be involved.

PMID- 23967319
TI  - Microdissection and chromosome painting of the alien chromosome in an addition
      line of wheat--Thinopyrum intermedium.
AB  - In this study, chromosome painting was developed and used to identify alien
      chromosomes in TAi-27, a wheat--Thinopyrum intermedium addition line, and the
      chromosomes of the three different genomes of Th. Intermedium. The smallest alien
      chromosome of TAi-27 was microdissected and its DNA amplified by DOP-PCR was used
      as a probe to hybridize with metaphase chromosomes of TAi-27 and Th. intermedium.
      Results showed that hybridization signals were observed in all regions of a pair
      of the smallest alien chromosomes and the pericentromeric area of another pair of
      alien chromosomes in TAi-27, indicating that the probe from microdissected
      chromosome is species specific. In Th. intermedium, 14 chromosomes had wide and
      strong hybridization signals distributed mainly on the pericentromere area and 9
      chromosomes with narrow and weak signals on the pericentromere area. The
      remaining chromosomes displayed a very weak or no signal. Sequential FISH/GISH on
      Th. intermedium chromosomes using the DNAs of microdissected chromosome,
      Pseudoroegneria spicata (St genome) and pDbH12 (a J(s) genome specific probe) as
      the probes indicated that the microdissected chromosome belonged to the St
      genome, three genomes (J(s) , J and St) in Th. intermedium could be
      distinguished, in which there is no hybridization signal on J genome that is
      similar to the genome of Th. bessarabicum. Our results showed that the smallest
      alien chromosomes may represent a truncated chromosome and the repetitive
      sequence distribution might be similar in different chromosomes within the St
      genome. However, the repetitive sequence distributions are different within the
      J(s) genome, within a single chromosome, and among different genomes in Th.
      intermedium. Our results suggested that chromosome painting could be feasible in
      some plants and useful in detecting chromosome variation and repetitive sequence
      distribution in different genomes of polyploidy plants, which is helpful for
      understanding the evolution of different genomes in polyploid plants.

PMID- 23967320
TI  - Enhanced sympathetic arousal in response to FMRI scanning correlates with task
      induced activations and deactivations.
AB  - It has been repeatedly shown that functional magnetic resonance imaging (fMRI)
      triggers distress and neuroendocrine response systems. Prior studies have
      revealed that sympathetic arousal increases, particularly at the beginning of the
      examination. Against this background it appears likely that those stress
      reactions during the scanning procedure may influence task performance and neural
      correlates. However, the question how sympathetic arousal elicited by the
      scanning procedure itself may act as a potential confounder of fMRI data remains
      unresolved today. Thirty-seven scanner naive healthy subjects performed a simple
      cued target detection task. Levels of salivary alpha amylase (sAA), as a
      biomarker for sympathetic activity, were assessed in samples obtained at several
      time points during the lab visit. SAA increased two times, immediately prior to
      scanning and at the end of the scanning procedure. Neural activation related to
      motor preparation and timing as well as task performance was positively
      correlated with the first increase. Furthermore, the first sAA increase was
      associated with task induced deactivation (TID) in frontal and parietal regions.
      However, these effects were restricted to the first part of the experiment.
      Consequently, this bias of scanner related sympathetic activation should be
      considered in future fMRI investigations. It is of particular importance for
      pharmacological investigations studying adrenergic agents and the comparison of
      groups with different stress vulnerabilities like patients and controls or
      adolescents and adults. 

PMID- 23967321
TI  - Analysis of expression, cellular localization, and function of three inhibitors
      of apoptosis (IAPs) from Litopenaeus vannamei during WSSV infection and in
      regulation of antimicrobial peptide genes (AMPs).
AB  - Inhibitors of apoptosis (IAPs) play important roles in apoptosis and NF-kappaB
      activation. In this study, we cloned and characterized three IAPs (LvIAP1-3) from
      the Pacific white shrimp, Litopenaeusvannamei. LvIAP1-3 proteins shared signature
      domains and exhibited significant similarities with other IAP family proteins.
      The tissue distributions of LvIAP1-3 were studied. The expression of LvIAP1-3 was
      induced in the muscle after white spot syndrome virus (WSSV) infection. LvIAP1
      expression in the gill, hemocytes, hepatopancreas, and intestine was responsive
      to WSSV and Vibrioalginolyticus infections. LvIAP2 expression in the gill,
      hemocytes, and hepatopancreas was also responsive to WSSV infection. The
      expression of LvIAP3 in the gill, hemocytes, and intestine was reduced after V.
      alginolyticus infection. When overexpressed in Drosophila S2 cells, GFP labeled
      LvIAP2 was distributed in the cytoplasm and appeared as speck-like aggregates in
      the nucleus. Both LvIAP1 and LvIAP3 were widely distributed throughout the
      cytoplasm and nucleus. The expression of LvIAP1, LvIAP2, and LvIAP3 was
      significantly knocked down by dsRNA-mediated gene silencing. In the gill of
      LvIAP1- or LvIAP3-silenced shrimp, the expression of WSSV VP28 was significantly
      higher than that of the dsGFP control group, suggesting that LvIAP1 and LvIAP3
      may play protective roles in host defense against WSSV infection. Intriguingly,
      the LvIAP2-silenced shrimp all died within 48 hours after dsLvIAP2 injection. In
      the hemocytes of LvIAP2-silenced shrimps, the expression of antimicrobial peptide
      genes (AMPs), including Penaeidins, lysozyme, crustins, Vibriopenaeicidae-induced
      cysteine and proline-rich peptides (VICPs), was significantly downregulated,
      while the expression of anti-lipopolysaccharide factors (ALFs) was upregulated.
      Moreover, LvIAP2 activated the promoters of the NF-kappaB pathway-controlled
      AMPs, such as shrimp Penaeidins and Drosophila drosomycin and attacin A, in
      Drosophila S2 cells. Taken together, these results reveal that LvIAP1 and LvIAP3
      might participate in the host defense against WSSV infection, and LvIAP2 might be
      involved in the regulation of shrimp AMPs. 

PMID- 23967322
TI  - Extrauterine listeriosis in the gravid mouse influences embryonic growth and
      development.
AB  - Gravid mice and other rodents inoculated with Listeria monocytogenes typically
      fail to clear an intrauterine infection and either succumb or expel their
      intrauterine contents. We took advantage of this property to investigate the
      effects of an extrauterine infection on parameters of pregnancy success. Pregnant
      mice were selected for our study if they showed no clinical signs of listeriosis
      following oral inoculation at 7.5 gestational days (gd), and had no detectable
      intrauterine colony forming units (cfu) at near term (18.5 gd). The range of oral
      doses employed was 106-108 cfu per mouse for two listerial serotype strains
      (4nonb and 1/2a). At all doses, inoculation resulted in a decrease in average
      near-term (18.5 gd) fetal weight per litter compared to sham inoculated controls.
      Additionally, embryonic death (indicated by intrauterine resorptions) was
      exhibited by some inoculated mice but was absent in all sham inoculated animals.
      In parallel experiments designed to detect possible loss of placental function,
      gravid uteruses were examined histopathologically and microbiologically 96 h
      after oral inoculation. Placental lesions were associated with high (> 106), but
      not low (< 102) or absent intrauterine cfu. In vitro, mouse embryonic
      trophoblasts were indistinguishable from mouse enterocytes in terms of their
      sensitivity to listerial exposure. A model consistent with our observations is
      one in which products (host or bacterial) generated during an acute infection
      enter embryos transplacentally and influences embryonic survival and slows normal
      growth in utero.

PMID- 23967323
TI  - Hyperbaric hyperoxia accelerates fracture healing in mice.
AB  - Increased oxygen tension influences bone metabolism. This study comprised two
      main experiments: one aimed to determine the bone mineral apposition and bone
      formation rates in vivo under hyperbaric hyperoxia (HBO), and the other aimed to
      evaluate the effects of exposure to HBO on fracture healing. In experiment 1,
      male mice were exposed to HBO [90 min/day at 90% O2 at 2 atmospheres absolute
      (ATA) for 5 days]. In experiment 2, an open femur fracture model was created in
      mice, followed by exposure to HBO 5 times/week (90 min/day at 90% O2 at 2 ATA)
      for 6 weeks after surgery. In experiment 1, HBO treatment significantly increased
      the mineral apposition and bone formation rates in the lumbar vertebra and femur
      and type 1 collagen alpha 1 and alkaline phosphatase mRNA expression in the
      lumbar vertebra. In experiment 2, at 2 weeks after fracture, the fracture callus
      was significantly larger in the HBO group than in the non-HBO group. Furthermore,
      at 4 and 6 weeks after fracture, radiographic findings showed accelerated
      fracture healing in the HBO group. At 6 weeks after fracture, femur stiffness and
      maximum load were significantly higher in the HBO group than in the non-HBO
      group. Urinary 8-hydroxy-2'-deoxyguanosine and plasma calcium concentrations were
      not significantly different between groups. These results suggest that exposure
      to HBO enhances bone anabolism and accelerates fracture healing without causing
      oxidative DNA damage or disruption of plasma calcium homeostasis.

PMID- 23967324
TI  - Clinical relevance of gain-of-function mutations of p53 in high-grade serous
      ovarian carcinoma.
AB  - PURPOSE: Inactivation of TP53, which occurs predominantly by missense mutations
      in exons 4-9, is a major genetic alteration in a subset of human cancer. In spite
      of growing evidence that gain-of-function (GOF) mutations of p53 also have
      oncogenic activity, little is known about the clinical relevance of these
      mutations. METHODS: The clinicopathological features of high-grade serous ovarian
      carcinoma (HGS-OvCa) patients with GOF p53 mutations were evaluated according to
      a comprehensive somatic mutation profile comprised of whole exome sequencing,
      mRNA expression, and protein expression profiles obtained from the Cancer Genome
      Atlas (TCGA). RESULTS: Patients with a mutant p53 protein (mutp53) with a GOF
      mutation showed higher p53 mRNA and protein expression levels than patients with
      p53 mutation with no evidence of GOF (NE-GOF). GOF mutations were more likely to
      occur within mutational hotspots, and at CpG sites, and resulted in mutp53 with
      higher functional severity (FS) scores. Clinically, patients with GOF mutations
      showed a higher frequency of platinum resistance (22/58, 37.9%) than patients
      with NE-GOF mutations (12/56, 21.4%) (p=0.054). Furthermore, patients with GOF
      mutations were more likely to develop distant metastasis (36/55, 65.5%) than
      local recurrence (19/55, 34.5%), whereas patients with NE-GOF mutations showed a
      higher frequency of locoregional recurrence (26/47, 55.3%) than distant
      metastasis (21/47, 44.7%) (p=0.035). There were no differences in overall or
      progression-free survival between patients with GOF or NE-GOF mutp53. CONCLUSION:
      This study demonstrates that patient with GOF mutp53 is characterized by a
      greater likelihood of platinum treatment resistance and distant metastatic
      properties in HGS-OvCa.

PMID- 23967325
TI  - Competence in Streptococcus pneumoniae is a response to an increasing mutational
      burden.
AB  - Competence for genetic transformation in Streptococcus pneumoniae has previously
      been described as a quorum-sensing trait regulated by a secreted peptide
      pheromone. Recently we demonstrated that competence is also activated by
      reduction in the accuracy of protein biosynthesis. We have now investigated
      whether errors upstream of translation in the form of random genomic mutations
      can provide a similar stimulus. Here we show that generation of a mutator
      phenotype in S. pneumoniae through deletions of mutX, hexA or hexB enhanced the
      expression of competence. Similarly, chemical mutagenesis with the nucleotide
      analog dPTP promoted development of competence. To investigate the relationship
      between mutational load and the activation of competence, replicate lineages of
      the mutX strain were serially passaged under conditions of relaxed selection
      allowing random accumulation of secondary mutations. Competence increased with
      propagation in these lineages but not in control lineages having wild-type mutX.
      Resequencing of these derived strains revealed between 1 and 9 single nucleotide
      polymorphisms (SNPs) per lineage, which were broadly distributed across the
      genome and did not involve known regulators of competence. Notably, the frequency
      of competence development among the sequenced strains correlated significantly
      with the number of nonsynonymous mutations that had been acquired. Together,
      these observations provide support for the hypothesis that competence in S.
      pneumoniae is regulated in response to the accumulated burden of coding mutations
      in the bacterial genome. In contrast to previously described DNA damage response
      systems that are activated by physical lesions in the chromosome, this
      pneumococcal pathway may represent a unique stress response system that monitors
      the coding integrity of the genome. 

PMID- 23967326
TI  - Psychiatric illness and intellectual disability in the Prader-Willi syndrome with
      different molecular defects--a meta analysis.
AB  - BACKGROUND AND OBJECTIVES: Several studies have suggested a difference in
      clinical features of intellectual ability and psychiatric illness in the Prader
      Willi syndrome (PWS) with the 15q11-q13 paternal deletion and maternal
      uniparental disomy (mUPD). Our objective was to appraise evidence on this
      association through a meta-analysis. METHODS: The electronic records PubMed and
      EMBASE from 1956 to 2012 were extracted for meta-analysis. Meta-analyses were
      performed by using fixed effect model. Mean difference, odds ratio, and 95%
      confidence interval were calculated. RESULTS: We retrieved a total of 744 PWS
      cases from 13 studies. These include 423 cases with paternal 15q11-q13 deletions
      and 318 cases of mUPD. Compare to the PWS cases with mUPD, PWS patients with the
      paternal 15q11-q13 deletion associated with significantly lower full scale IQ
      (FSIQ) [mean difference (MD), -2.69; 95%CI, -4.86 to -0.52; p=0.02] and verbal IQ
      (VIQ) (MD, -7.5; 95%CI, -9.75 to -5.26; p<0.00001) but higher performance IQ
      (PIQ) (MD, 4.02; 95%CI, 1.13 to 6.91; p=0.006). In contrast, PWS patients with
      mUPD are associated with significantly higher risk of psychiatric illness [odds
      rate (OR), 0.14; 95%CI, 0.08 to 0.23; p<0.00001] and higher risk of bipolar
      disorder (OR, 0.04; 95%CI, 0.01 to 0.23; p=0.0002). CONCLUSIONS: Significant
      different clinical features of cognitive development and psychiatric illness are
      associated with PWS with different molecular defects. These findings provide
      support for evidence based practice to evaluate and manage the PWS syndrome with
      different molecular defects.

PMID- 23967327
TI  - Hypoxia-inducible factor-1alpha and interleukin 33 form a regulatory circuit to
      perpetuate the inflammation in rheumatoid arthritis.
AB  - Hyperplasia of synovial fibroblasts, infiltration with inflammatory cytokines,
      and tissue hypoxia are the major characteristics of rheumatoid arthritis (RA).
      Interleukin 33 (IL-33) is a newly identified inflammatory cytokine exacerbating
      the disease severity of RA. Hypoxia-inducible factor-1alpha (HIF-1alpha) showed
      increased expression in RA synovium and could regulate a number of inflammatory
      cytokine productions. Nevertheless, its correlation with IL-33 remains largely
      unknown. Here, we showed that elevated levels of IL-33 were demonstrated in RA
      patient synovial fluids, with upregulated expression of HIF-1alpha and IL-33 in
      the synovial fibroblasts. Knocking down HIF-1alpha compromised IL-33 expression
      in rheumatoid arthritis synovial fibroblasts (RASF), while enforcing HIF-1alpha
      expression in RASF substantially upregulated IL-33 levels. HIF-1alpha promoted
      the activation of the signalling pathways controlling IL-33 production,
      particularly the p38 and ERK pathways. Moreover, we showed for the first time
      that IL-33 in turn could induce more HIF-1alpha expression in RASF, thus forming
      a HIF-1alpha/IL-33 regulatory circuit that would perpetuate the inflammatory
      process in RA. Targeting this pathological pathway and HIF-1alpha may provide new
      therapeutic strategies for overcoming the persistent and chronic inflammatory
      disease. 

PMID- 23967328
TI  - Association study of Val66Met polymorphism in brain-derived neurotrophic factor
      gene with clozapine-induced metabolic syndrome: preliminary results.
AB  - The prevalence of the metabolic syndrome (MetS) is higher among patients
      receiving atypical antipsychotics (AAPs) treatment, and even among AAPs,
      treatment with clozapine has been shown to be associated with a higher long-term
      incidence rate of MetS. Likewise, brain-derived neurotrophic factor (BDNF)
      deficiency has been reported to result in metabolic traits, such as increased
      food intake, hyperphagia and obesity, etc. In this study, we hypothesized that a
      functional polymorphism (Val66Met) in the BDNF gene may confer susceptibility to
      clozapine-induced MetS, potentially in a sex-specific manner, since an
      interaction between Val66Met polymorphism and sex was observed in our previous
      studies. A total of 199 schizophrenia patients being treated with clozapine were
      divided into two groups, MetS and non-MetS, based on the diagnostic criteria of
      the National Cholesterol Education Program's Adult Treatment Panel III. We
      genotyped the Val66Met polymorphism, and measured the serum levels of fasting
      glucose (GLU), triglyceride (TG) and high density lipoprotein cholesterol (HDL).
      There was a trend indicating a significant association between the homozygous
      Met/Met genotype and MetS in male patients (OR = 2.39; 95% CI: 1.05-5.41; p =
      0.039; corrected p = 0.078). Among the six risk factors listed in the ATPIII
      criteria, we found a significant association between fasting GLU levels and
      Val66Met polymorphism in males (p = 0.005; corrected p = 0.03), but not in
      females (p = 0.65). Post-hoc analysis in males revealed that the Met/Met carriers
      had significant higher levels of fasting GLU than those with Val/Val or Val/Met
      genotypes (p = 0.007; corrected p = 0.042 and p = 0.002; corrected p = 0.012,
      respectively). In conclusion, we observed a weak association between the Val66Met
      polymorphism and clozapine-induced MetS in a sex-specific manner. While
      preliminary, such findings prompt further, large-scale longitudinal studies to
      replicate these findings. 

PMID- 23967329
TI  - Association signals unveiled by a comprehensive gene set enrichment analysis of
      dental caries genome-wide association studies.
AB  - Gene set-based analysis of genome-wide association study (GWAS) data has recently
      emerged as a useful approach to examine the joint effects of multiple risk loci
      in complex human diseases or phenotypes. Dental caries is a common, chronic, and
      complex disease leading to a decrease in quality of life worldwide. In this
      study, we applied the approaches of gene set enrichment analysis to a major
      dental caries GWAS dataset, which consists of 537 cases and 605 controls. Using
      four complementary gene set analysis methods, we analyzed 1331 Gene Ontology (GO)
      terms collected from the Molecular Signatures Database (MSigDB). Setting false
      discovery rate (FDR) threshold as 0.05, we identified 13 significantly associated
      GO terms. Additionally, 17 terms were further included as marginally associated
      because they were top ranked by each method, although their FDR is higher than
      0.05. In total, we identified 30 promising GO terms, including 'Sphingoid
      metabolic process,' 'Ubiquitin protein ligase activity,' 'Regulation of cytokine
      secretion,' and 'Ceramide metabolic process.' These GO terms encompass broad
      functions that potentially interact and contribute to the oral immune response
      related to caries development, which have not been reported in the standard
      single marker based analysis. Collectively, our gene set enrichment analysis
      provided complementary insights into the molecular mechanisms and polygenic
      interactions in dental caries, revealing promising association signals that could
      not be detected through single marker analysis of GWAS data. 

PMID- 23967330
TI  - A Tet-on system for DRD1-expressing cells.
AB  - Cells expressing the dopamine D1 receptor (DRD1) have significant functional
      roles in diverse physiological processes including locomotion and drug addiction.
      The present work presents a novel in vivo DRD1-Bacterial Artificial Chromosome
      (BAC) Tet-on system allowing for the inducible activation of tet-operated
      transgenes specifically within DRD1-expressing cells of transgenic mice. It is
      shown that the DRD1-rtTA BAC-driven expression of a tet-operated reporter is
      under tight regulation by doxycycline and is restricted to DRD1-expressing brain
      regions. The model will be a useful research tool in studies of movement and
      reward and associated pathologies such as Parkinson's disease and addiction. 

PMID- 23967331
TI  - Jellyfish body plans provide allometric advantages beyond low carbon content.
AB  - Jellyfish form spectacular blooms throughout the world's oceans. Jellyfish body
      plans are characterised by high water and low carbon contents which enables them
      to grow much larger than non-gelatinous animals of equivalent carbon content and
      to deviate from non-gelatinous pelagic animals when incorporated into allometric
      relationships. Jellyfish have, however, been argued to conform to allometric
      relationships when carbon content is used as the metric for comparison. Here we
      test the hypothesis that differences in allometric relationships for several key
      functional parameters remain for jellyfish even after their body sizes are scaled
      to their carbon content. Data on carbon and nitrogen contents, rates of
      respiration, excretion, growth, longevity and swimming velocity of jellyfish and
      other pelagic animals were assembled. Allometric relationships between each
      variable and the equivalent spherical diameters of jellyfish and other pelagic
      animals were compared before and after sizes of jellyfish were standardised for
      their carbon content. Before standardisation, the slopes of the allometric
      relationships for respiration, excretion and growth were the same for jellyfish
      and other pelagic taxa but the intercepts differed. After standardisation, slopes
      and intercepts for respiration were similar but excretion rates of jellyfish were
      10* slower, and growth rates 2* faster than those of other pelagic animals.
      Longevity of jellyfish was independent of size. The slope of the allometric
      relationship of swimming velocity of jellyfish differed from that of other
      pelagic animals but because they are larger jellyfish operate at Reynolds numbers
      approximately 10* greater than those of other pelagic animals of comparable
      carbon content. We conclude that low carbon and high water contents alone do not
      explain the differences in the intercepts or slopes of the allometric
      relationships of jellyfish and other pelagic animals and that the evolutionary
      longevity of jellyfish and their propensity to form blooms is facilitated by
      their unique body plans. 

PMID- 23967332
TI  - Histological and micro-CT evidence of stigmatic rostellum receptivity promoting
      auto-pollination in the madagascan orchid Bulbophyllum bicoloratum.
AB  - BACKGROUND: The rostellum, a projecting part of the gynostemium in orchid
      flowers, separates the anther(s) from the stigma and thus commonly prevents auto
      pollination. Nonetheless, as a modified (usually distal) portion of the median
      stigma lobe, the rostellum has been frequently invoked of having re-gained a
      stigmatic function in rare cases of orchid auto-pollination. Here it is shown
      that a newly discovered selfing variant of Madagascan Bulbophyllumbicoloratum has
      evolved a modified rostellum allowing the penetration of pollen tubes from in
      situ pollinia. METHODS: Gynostemium micro-morphology and anatomy of selfing and
      outcrossing variants of B. bicoloratum was studied by using light and scanning
      electron microscopy and histological sections. Pollen tube growth in the selfing
      variant was further observed via X-ray computed microtomography (micro-CT),
      providing 3D reconstructions of floral tissues at a micron scale. FINDINGS:
      Selfing variants possess a suberect ('displaced') rostellum rather than the
      conventional, erect type. Very early in anthesis, the pollinia of selfers are
      released from the anther and slide down onto the suberect rostellum, where pollen
      tube growth preferentially occurs through the non-vascularized, i.e. rear
      (adaxial) and (semi-) lateral parts. This penetrated tissue is comprised of a
      thin layer of elongate and loosely arranged cells, embedded in stigmatic
      exudates, as also observed in the stigmatic cavity of both selfing and
      outcrossing variants. CONCLUSIONS: Our results provide the first solid evidence
      of a stigmatic function for the rostellum in orchid flowers, thereby
      demonstrating for the first time the feasibility of the micro-CT technique for
      accurately visualizing pollen tube growth in flowering plants. Rostellum
      receptivity in B. bicoloratum probably uniquely evolved as an adaptation for
      reproductive assurance from an outcrossing ancestor possessing an erect (non
      receptive) rostellum. These findings open up new avenues in the investigation of
      an organ that apparently re-gained its 'primordial function' of being penetrated
      by pollen tubes.

PMID- 23967333
TI  - H3K27 demethylase, JMJD3, regulates fragmentation of spermatogonial cysts.
AB  - The spermatogonial stem cell (SSC) compartment is maintained by self-renewal of
      stem cells as well as fragmentation of differentiating spermatogonia through
      abscission of intercellular bridges in a random and stochastic manner. The
      molecular mechanisms that regulate this reversible developmental lineage remain
      to be elucidated. Here, we show that histone H3K27 demethylase, JMJD3 (KDM6B),
      regulates the fragmentation of spermatogonial cysts. Down-regulation of Jmjd3 in
      SSCs promotes an increase in undifferentiated spermatogonia but does not affect
      their differentiation. Germ cell-specific Jmjd3 null male mice have larger testes
      and sire offspring for a longer period compared to controls, likely secondary to
      increased and prolonged maintenance of the spermatogonial compartment. Moreover,
      JMJD3 deficiency induces frequent fragmentation of spermatogonial cysts by
      abscission of intercellular bridges. These results suggest that JMJD3 controls
      the spermatogonial compartment through the regulation of fragmentation of
      spermatogonial cysts and this mechanism may be involved in maintenance of diverse
      stem cell niches. 

PMID- 23967335
TI  - ESTs analysis reveals putative genes involved in symbiotic seed germination in
      Dendrobium officinale.
AB  - Dendrobiumofficinale (Orchidaceae) is one of the world's most endangered plants
      with great medicinal value. In nature, D. officinale seeds must establish
      symbiotic relationships with fungi to germinate. However, the molecular events
      involved in the interaction between fungus and plant during this process are
      poorly understood. To isolate the genes involved in symbiotic germination, a
      suppression subtractive hybridization (SSH) cDNA library of symbiotically
      germinated D. officinale seeds was constructed. From this library, 1437 expressed
      sequence tags (ESTs) were clustered to 1074 Unigenes (including 902 singletons
      and 172 contigs), which were searched against the NCBI non-redundant (NR) protein
      database (E-value cutoff, e(-5)). Based on sequence similarity with known
      proteins, 579 differentially expressed genes in D. officinale were identified and
      classified into different functional categories by Gene Ontology (GO), Clusters
      of orthologous Groups of proteins (COGs) and Kyoto Encyclopedia of Genes and
      Genomes (KEGG) pathways. The expression levels of 15 selected genes emblematic of
      symbiotic germination were confirmed via real-time quantitative PCR. These genes
      were classified into various categories, including defense and stress response,
      metabolism, transcriptional regulation, transport process and signal transduction
      pathways. All transcripts were upregulated in the symbiotically germinated seeds
      (SGS). The functions of these genes in symbiotic germination were predicted.
      Furthermore, two fungus-induced calcium-dependent protein kinases (CDPKs), which
      were upregulated 6.76- and 26.69-fold in SGS compared with un-germinated seeds
      (UGS), were cloned from D. officinale and characterized for the first time. This
      study provides the first global overview of genes putatively involved in D.
      officinale symbiotic seed germination and provides a foundation for further
      functional research regarding symbiotic relationships in orchids. 

PMID- 23967334
TI  - Functions of huntingtin in germ layer specification and organogenesis.
AB  - Huntington's disease (HD) is a neurodegenerative disease caused by abnormal
      polyglutamine expansion in the huntingtin protein (Htt). Although both Htt and
      the HD pathogenic mutation (mHtt) are implicated in early developmental events,
      their individual involvement has not been adequately explored. In order to better
      define the developmental functions and pathological consequences of the normal
      and mutant proteins, respectively, we employed embryonic stem cell (ESC)
      expansion, differentiation and induction experiments using huntingtin knock-out
      (KO) and mutant huntingtin knock-in (Q111) mouse ESC lines. In KO ESCs, we
      observed impairments in the spontaneous specification and survival of ectodermal
      and mesodermal lineages during embryoid body formation and under inductive
      conditions using retinoic acid and Wnt3A, respectively. Ablation of BAX improves
      cell survival, but failed to correct defects in germ layer specification. In
      addition, we observed ensuing impairments in the specification and maturation of
      neural, hepatic, pancreatic and cardiomyocyte lineages. These developmental
      deficits occurred in concert with alterations in Notch, Hes1 and STAT3 signaling
      pathways. Moreover, in Q111 ESCs, we observed differential developmental stage
      specific alterations in lineage specification and maturation. We also observed
      changes in Notch/STAT3 expression and activation. Our observations underscore
      essential roles of Htt in the specification of ectoderm, endoderm and mesoderm,
      in the specification of neural and non-neural organ-specific lineages, as well as
      cell survival during early embryogenesis. Remarkably, these developmental events
      are differentially deregulated by mHtt, raising the possibility that HD
      associated early developmental impairments may contribute not only to region
      specific neurodegeneration, but also to non-neural co-morbidities. 

PMID- 23967336
TI  - CXCL1 contributes to beta-amyloid-induced transendothelial migration of monocytes
      in Alzheimer's disease.
AB  - BACKGROUND: Bone marrow-derived microglia that originates in part from
      hematopoietic cells, and more particularly from monocytes preferentially attach
      to amyloid deposition in brains of Alzheimer's disease (AD). However, the
      mechanism of monocytes recruited into the amyloid plaques with an accelerated
      process in AD is unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here we reported that
      monocytes from AD patients express significantly higher chemokine (C-X-C motif)
      ligand 1 (CXCL1) compared to age-matched controls. AD patient's monocytes or
      CXCL1-overexpressing THP-1 cells had enhanced ability of beta-amyloid (Abeta)
      induced transendothelial migration and Abeta-induced transendothelial migration
      for AD patient's monocytes or CXCL1-overexpressing THP-1 cells was almost
      abrogated by anti-CXCL1 antibody. Furthermore, monocytes derived from a
      transgenic mouse model of AD also expressed significantly higher CXCL1.
      CD11b+CD45(hi) population of cells that were recruited from the peripheral blood
      were markedly bolcked in APP mouse brain by anti-CXCL1 antibody. Accordingly, in
      response to Abeta, human brain microvascular endothelial cells (HBMEC)
      significantly up-regulated CXC chemokine receptor 2 (CXCR2) expression, which was
      the only identified receptor for CXCL1. In addition, a high level expression of
      CXCR2 in HBMEC significantly promoted the CXCL1-overexpressing THP-1 cells
      transendothelial migration, which could be was abrogated by anti-CXCR2 antibody.
      Further examination of possible mechanisms found that CXCL1-overexpressing THP-1
      cells induced transendothelial electrical resistance decrease, horseradish
      peroxidase flux increase, ZO-1 discontinuous and occludin re-distribution from
      insoluble to soluble fraction through interacting with CXCR2. ROCK inhibitor,
      Y27632, could block CXCL1-overexpressing THP-1 cells transendothelial migration,
      whereas other inhibitors had no effects. CONCLUSIONS/SIGNIFICANCE: The present
      data indicate that monocytes derived from AD patients overexpressing CXCL1, which
      is a determinant for Abeta-induced transendothelial migration. CXCL1 expressed by
      monocytes and CXCR2 on HBMEC is involved in monocytes migrating from blood to
      brain in AD patients.

PMID- 23967337
TI  - Subunit vaccine consisting of multi-stage antigens has high protective efficacy
      against Mycobacterium tuberculosis infection in mice.
AB  - To search for more effective tuberculosis (TB) subunit vaccines, antigens
      expressed in different growth stages of Mycobacterium tuberculosis (M.
      tuberculosis), such as RpfE (Rv2450c) produced in the stage of resuscitation,
      Mtb10.4 (Rv0288), Mtb8.4 (Rv1174c), ESAT6 (Rv3875), Ag85B (Rv1886c) mainly
      secreted by replicating bacilli, and HspX (Rv2031c) highly expressed in dormant
      bacilli, were selected to construct six fusion proteins: ESAT6-Ag85B-MPT64190-198
      Mtb8.4 (EAMM), Mtb10.4-HspX (MH), ESAT6-Mtb8.4, Mtb10.4-Ag85B, ESAT6-Ag85B, and
      ESAT6-RpfE. The six fusion proteins were separately emulsified in an adjuvant
      composed of N,N'-dimethyl-N, N'-dioctadecylammonium bromide (DDA),
      polyribocytidylic acid (poly I:C) and gelatin to construct subunit vaccines, and
      their protective effects against M. tuberculosis infection were evaluated in
      C57BL/6 mice. Furthermore, the boosting effects of EAMM and MH in the adjuvant of
      DDA plus trehalose 6,6'-dimycolate (TDM) on BCG-induced immunity were also
      evaluated. It was found that the six proteins were stably produced in E. coli and
      successfully purified by chromatography. Among them, EAMM presented the most
      effective protection against M. tuberculosis. Interestingly, the mice that
      received EAMM+MH had significantly lower bacterial counts in the lungs and
      spleens than the single protein vaccinated groups, and had the same effect as
      those that received BCG. In addition, EAMM and MH could improve BCG-primed
      protective efficacy against M. tuberculosis infection in mice. In conclusion, the
      combination of EAMM and MH containing antigens from both replicating and dormant
      stages of the bacilli could induce robust immunity against M. tuberculosis
      infection in mice and may serve as promising subunit vaccine candidate. 

PMID- 23967338
TI  - Flight phases in the song of skylarks: impact on acoustic parameters and coding
      strategy.
AB  - Skylarks inhabit open fields and perform an aerial song display which serves as a
      territorial signal. The particularly long and elaborate structure of this song
      flight raises questions about the impact of physical and energetic constraints
      acting on a communication signal. Song produced during the three distinct phases
      of the flight - ascending, level and descending phase could be subject to
      different constraints, serve different functions and encode different types of
      information. We compared song parameters during the ascending and the level
      phases. We found that the structure of the song varied with the phase of the
      flight. In particular, song had a higher tempo when skylarks were ascending which
      might be related to higher oxygen and energetic demands. We also explored which
      phase of the song flight might encode individuality. Earlier studies reported
      that skylarks reduced their territorial response to established neighbours if the
      neighbour song was broadcasted from the correct adjacent boundary, but reacted
      aggressively if the neighbour songs were broadcasted from an incorrect boundary
      (mimicking a displaced neighbour). Such differential response provides some
      evidence for individual recognition. Here, we exposed subjects to playback
      stimuli of neighbour song in which we had replaced either the song produced
      during the level or the ascending phase by the relevant song of the neighbour
      from the incorrect border. Singing response was higher towards stimuli in which
      the 'level phase song' was replaced, indicating that skylarks could be able to
      recognise their neighbours based on song of this phase. Thus, individuality seems
      to be primarily coded in the level phase of the flight song. 

PMID- 23967340
TI  - Fabrication of dense non-circular nanomagnetic device arrays using self-limiting
      low-energy glow-discharge processing.
AB  - We describe a low-energy glow-discharge process using reactive ion etching system
      that enables non-circular device patterns, such as squares or hexagons, to be
      formed from a precursor array of uniform circular openings in polymethyl
      methacrylate, PMMA, defined by electron beam lithography. This technique is of a
      particular interest for bit-patterned magnetic recording medium fabrication,
      where close packed square magnetic bits may improve its recording performance.
      The process and results of generating close packed square patterns by self
      limiting low-energy glow-discharge are investigated. Dense magnetic arrays formed
      by electrochemical deposition of nickel over self-limiting formed molds are
      demonstrated. 

PMID- 23967339
TI  - ICOS-expressing lymphocytes promote resolution of CD8-mediated lung injury in a
      mouse model of lung rejection.
AB  - Acute rejection, a common complication of lung transplantation, may promote
      obliterative bronchiolitis leading to graft failure in lung transplant
      recipients. During acute rejection episodes, CD8(+) T cells can contribute to
      lung epithelial injury but the mechanisms promoting and controlling CD8-mediated
      injury in the lung are not well understood. To study the mechanisms regulating
      CD8(+) T cell-mediated lung rejection, we used a transgenic model in which
      adoptively transferred ovalbumin (OVA)-specific cytotoxic T lymphocytes (CTL)
      induce lung injury in mice expressing an ovalbumin transgene in the small airway
      epithelium of the lungs (CC10-OVA mice). The lung pathology is similar to
      findings in humans with acute lung transplant. In the presence of an intact
      immune response the inflammation resolves by day 30. Using CC10-OVA.RAG(-/-)
      mice, we found that CD4(+) T cells and ICOS(+/+) T cells were required for
      protection against lethal lung injury, while neutrophil depletion was not
      protective. In addition, CD4(+)Foxp3 (+) ICOS(+) T cells were enriched in the
      lungs of animals surviving lung injury and ICOS(+/+) Tregs promoted survival in
      animals that received ICOS(-/-) T cells. Direct comparison of ICOS(-/-) Tregs to
      ICOS(+/+) Tregs found defects in vitro but no differences in the ability of ICOS(
      /-) Tregs to protect from lethal lung injury. These data suggest that ICOS
      affects Treg development but is not necessarily required for Treg effector
      function. 

PMID- 23967341
TI  - FERM domain containing protein 7 interacts with the Rho GDP dissociation
      inhibitor and specifically activates Rac1 signaling.
AB  - The FERM domain containing protein 7 gene (FRMD7) associated with the X-linked
      disorder idiopathic congenital nystagmus (ICN) is involved in the regulation of
      neurite elongation during neuronal development. Members of the Rho family of
      small G-proteins (Rho GTPases) are key regulators of the actin cytoskeleton and
      are implicated in the control of neuronal morphology. The Rho GDP dissociation
      inhibitor alpha, RhoGDIalpha, the main regulator of Rho GTPases, can form a
      complex with the GDP-bound form of Rho GTPases and inhibit their activation.
      Here, we demonstrate that the full length of the mouse FRMD7, rather than the N
      terminus or the C-terminus alone, directly interacts with RhoGDIalpha and
      specifically initiates Rac1 signaling in mouse neuroblastoma cell line (neuro
      2a). Moreover, we show that wild-type human FRMD7 protein is able to activate
      Rac1 signaling by interacting with RhoGDIalpha and releasing Rac1 from Rac1
      RhoGDIalpha complex. However, two missense mutations (c.781C>G and c.886G>C) of
      human FRMD7 proteins weaken the ability to interact with RhoGDIalpha and release
      less Rac1, that induce the activation of Rac1 to a lesser degree; while an
      additional mutant, c.1003C>T, which results in a C-terminal truncated protein,
      almost fails to interact with RhoGDIalpha and to activate Rac1 signaling.
      Collectively, these results suggest that FRMD7 interacts with one of the Rho
      GTPase regulators, RhoGDIalpha, and activates the Rho subfamily member Rac1,
      which regulates reorganization of actin filaments and controls neuronal
      outgrowth. We predict that human mutant FRMD7 thus influences Rac1 signaling
      activation, which can lead to abnormal neuronal outgrowth and cause the X-linked
      ICN. 

PMID- 23967342
TI  - Cytokine profiling in immigrants with clinical malaria after extended periods of
      interrupted exposure to Plasmodium falciparum.
AB  - Immunity to malaria is believed to wane with time in the absence of exposure to
      Plasmodium falciparum infection, but immunoepidemiological data on longevity of
      immunity remain controversial. We quantified serum cytokines and chemokines by
      suspension array technology as potential biomarkers for durability of immunity in
      immigrants with clinical malaria after years without parasite exposure. These
      were compared to serum/plasma profiles in naive adults (travelers) and semi
      immune adults under continuous exposure, with malaria, along with immigrant and
      traveler patients without malaria. Immigrants had higher levels of IL-2, IL-5 and
      IL-8 compared to semi-immune adults with malaria (P<=0.0200). Time since
      immigration correlated with increased IL-2 (rho=0.2738P=0.0495) and IFN-gamma
      (rho=0.3044P=0.0282). However, immigrants did not show as high IFN-gamma
      concentrations as travelers during a first malaria episode (P<0.0001). Immigrants
      and travelers with malaria had higher levels of IFN-gamma, IL-6, and IL-10
      (P<0.0100) than patients with other diseases, and IL-8 and IL-1beta were elevated
      in immigrants with malaria (P<0.0500). Therefore, malaria patients had a
      characteristic strong pro-inflammatory/Th1 signature. Upon loss of exposure,
      control of pro-inflammatory responses and tolerance to P. falciparum appeared to
      be reduced. Understanding the mechanisms to maintain non-pathogenic effector
      responses is important to develop new malaria control strategies. 

PMID- 23967343
TI  - Prolonged minocycline treatment impairs motor neuronal survival and glial
      function in organotypic rat spinal cord cultures.
AB  - BACKGROUND: Minocycline, a second-generation tetracycline antibiotic, exhibits
      anti-inflammatory and neuroprotective effects in various experimental models of
      neurological diseases, such as stroke, Alzheimer's disease, amyotrophic lateral
      sclerosis and spinal cord injury. However, conflicting results have prompted a
      debate regarding the beneficial effects of minocycline. METHODS: In this study,
      we analyzed minocycline treatment in organotypic spinal cord cultures of neonatal
      rats as a model of motor neuron survival and regeneration after injury.
      Minocycline was administered in 2 different concentrations (10 and 100 uM) at
      various time points in culture and fixed after 1 week. RESULTS: Prolonged
      minocycline administration decreased the survival of motor neurons in the
      organotypic cultures. This effect was strongly enhanced with higher
      concentrations of minocycline. High concentrations of minocycline reduced the
      number of DAPI-positive cell nuclei in organotypic cultures and simultaneously
      inhibited microglial activation. Astrocytes, which covered the surface of the
      control organotypic cultures, revealed a peripheral distribution after early
      minocycline treatment. Thus, we further analyzed the effects of 100 uM
      minocycline on the viability and migration ability of dispersed primary glial
      cell cultures. We found that minocycline reduced cell viability, delayed wound
      closure in a scratch migration assay and increased connexin 43 protein levels in
      these cultures. CONCLUSIONS: The administration of high doses of minocycline was
      deleterious for motor neuron survival. In addition, it inhibited microglial
      activation and impaired glial viability and migration. These data suggest that
      especially high doses of minocycline might have undesired affects in treatment of
      spinal cord injury. Further experiments are required to determine the conditions
      for the safe clinical administration of minocycline in spinal cord injured
      patients.

PMID- 23967344
TI  - Dissection of a single rat muscle-tendon complex changes joint moments exerted by
      neighboring muscles: implications for invasive surgical interventions.
AB  - The aim of this paper is to investigate mechanical functioning of a single
      skeletal muscle, active within a group of (previously) synergistic muscles. For
      this purpose, we assessed wrist angle-active moment characteristics exerted by a
      group of wrist flexion muscles in the rat for three conditions: (i) after
      resection of the upper arm skin; (ii) after subsequent distal tenotomy of flexor
      carpi ulnaris muscle (FCU); and (iii) after subsequent freeing of FCU distal
      tendon and muscle belly from surrounding tissues (MT dissection). Measurements
      were performed for a control group and for an experimental group after recovery
      (5 weeks) from tendon transfer of FCU to extensor carpi radialis (ECR) insertion.
      To assess if FCU tenotomy and MT dissection affects FCU contributions to wrist
      moments exclusively or also those of neighboring wrist flexion muscles, these
      data were compared to wrist angle-moment characteristics of selectively activated
      FCU. FCU tenotomy and MT dissection decreased wrist moments of the control group
      at all wrist angles tested, including also angles for which no or minimal wrist
      moments were measured when activating FCU exclusively. For the tendon transfer
      group, wrist flexion moment increased after FCU tenotomy, but to a greater extent
      than can be expected based on wrist extension moments exerted by selectively
      excited transferred FCU. We conclude that dissection of a single muscle in any
      surgical treatment does not only affect mechanical characteristics of the target
      muscle, but also those of other muscles within the same compartment. Our results
      demonstrate also that even after agonistic-to-antagonistic tendon transfer,
      mechanical interactions with previously synergistic muscles do remain present. 

PMID- 23967345
TI  - Shizukaol D isolated from Chloranthus japonicas inhibits AMPK-dependent lipid
      content in hepatic cells by inducing mitochondrial dysfunction.
AB  - This study is the first to demonstrate that shizukaol D, a natural compound
      isolated from Chloranthusjaponicus, can activate AMP- activated protein kinase
      (AMPK), a key sensor and regulator of intracellular energy metabolism, leading to
      a decrease in triglyceride and cholesterol levels in HepG2 cells. Furthermore, we
      found that shizukaol D induces mitochondrial dysfunction by depolarizing the
      mitochondrial membrane and suppressing energy production, which may result in
      AMPK activation. Our results provide a possible link between mitochondrial
      dysfunction and AMPK activation and suggest that shizukaol D might be used to
      treat metabolic syndrome. 

PMID- 23967346
TI  - A double WAP domain-containing protein Es-DWD1 from Eriocheir sinensis exhibits
      antimicrobial and proteinase inhibitory activities.
AB  - Whey acidic proteins (WAP) belong to a large gene family of antibacterial
      peptides, which are critical in the host immune response against microbial
      invasion. The common feature of these proteins is a single WAP domain maintained
      by at least one four-disulfide core (4-DSC) structure rich in cysteine residues.
      In this study, a double WAP domain (DWD)-containing protein, Es-DWD1, was first
      cloned from the Chinese mitten crab (Eriocheirsinensis). The full-length Es
      DWD1cDNA was 1193 bp, including a 411 bp open reading frame (ORF) encoding 136
      amino acids with a signal peptide of 22 amino acids in the N-terminus. A
      comparison with other reported invertebrate and vertebrate sequences revealed the
      presence of WAP domains characteristic of WAP superfamilies. As determined by
      quantitative real-time RT-PCR, Es-DWD1 transcripts were ubiquitously expressed in
      all tissues, but it was up-regulated in hemocytes post-challenge with pathogen
      associated molecular patterns (PAMPs). The mature recombinant Es-DWD1 (rEs-DWD1)
      protein exhibited different binding activities to bacteria and fungus. Moreover,
      rEs-DWD1 could exert agglutination activities against Bacillus subtilis and
      Pichiapastoris and demonstrated inhibitory activities against the growth of
      Staphylococcus aureus, Aeromonas hydrophila and P. pastoris. Furthermore, rEs
      DWD1 showed a specific protease inhibitory activity in B. subtilis. Coating of
      rEs-DWD1 onto agarose beads enhanced encapsulation of the beads by crab
      hemocytes. Collectively, the results suggest that Es-DWD1 is a double WAP domain
      containing protein with antimicrobial and proteinase inhibitory activities, which
      play significant roles in the immunity of crustaceans. 

PMID- 23967347
TI  - High antibody responses against Plasmodium falciparum in immigrants after
      extended periods of interrupted exposure to malaria.
AB  - BACKGROUND: Malaria immunity is commonly believed to wane in the absence of
      Plasmodium falciparum exposure, based on limited epidemiological data and short
      lived antibody responses in some longitudinal studies in endemic areas. METHODS:
      A cross-sectional study was conducted among sub-Saharan African adults residing
      in Spain for 1 up to 38 years (immigrants) with clinical malaria (n=55) or
      without malaria (n=37), naive adults (travelers) with a first clinical malaria
      episode (n=20) and life-long malaria exposed adults from Mozambique (semi-immune
      adults) without malaria (n=27) or with clinical malaria (n=50). Blood samples
      were collected and IgG levels against the erythrocytic antigens AMA-1 and MSP-142
      (3D7 and FVO strains), EBA-175 and DBL-alpha were determined by Luminex. IgG
      levels against antigens on the surface of infected erythrocytes (IEs) were
      measured by flow cytometry. RESULTS: Immigrants without malaria had lower IgG
      levels than healthy semi-immune adults regardless of the antigen tested
      (P<=0.026), but no correlation was found between IgG levels and time since
      migration. Upon reinfection, immigrants with malaria had higher levels of IgG
      against all antigens than immigrants without malaria. However, the magnitude of
      the response compared to semi-immune adults with malaria depended on the antigen
      tested. Thus, immigrants had higher IgG levels against AMA-1 and MSP-142
      (P<=0.015), similar levels against EBA-175 and DBL-alpha, and lower levels
      against IEs (P<=0.016). Immigrants had higher IgG levels against all antigens
      tested compared to travelers (P<=0.001), both with malaria. CONCLUSIONS: Upon
      cessation of malaria exposure, IgG responses to malaria-specific antigens were
      maintained to a large extent, although the conservation and the magnitude of the
      recall response depended on the nature of the antigen. Studies on immigrant
      populations can shed light on the factors that determine the duration of malaria
      specific antibody responses and its effect on protection, with important
      implications for future vaccine design and public health control measures.

PMID- 23967348
TI  - Evaluation of genetic polymorphisms in patients with multiple chemical
      sensitivity.
AB  - OBJECTIVE: Multiple chemical sensitivity (MCS) is a chronic medical condition
      characterized by symptoms that the affect an individual's response to low-level
      chemical exposure. In this study, we identified a chemical sensitive population
      (CSP) and investigated the effect of genetic polymorphisms on their risk of
      chemical sensitivity. METHODS: A quick environment exposure sensitivity (QEESI)
      questionnaire was used to survey 324 Japanese male workers whose DNA samples had
      been collected and stored. The following genes, which encode enzymes affecting
      the metabolic activation of a large number of xenobiotic compounds, were selected
      and analyzed in order to determine their influence on genetic predisposition to
      CSP: cytochrome P450 (CYP) 2E1, N-acetyl transferase (NAT) 2, glutathione S
      transferase (GST) M1, GSTT1, GSTP1, low Km aldehyde dehydrogenase (ALDH2), and
      superoxide dismutase (SOD) 2. RESULTS: Significant case-control distributed
      differences were observed in SOD2 polymorphisms and allele frequency distribution
      in high chemical sensitive subjects. Both the significant adjusted OR of 4.30
      (95% CI, 1.23-15.03) and 4.53 (95% CI, 1.52-13.51) were observed in SOD2 Ala/Ala
      and Val/Ala compared to Val/Val and in SOD2 Ala/Ala compared to Val/Ala compared
      to Val/Val genetic analysis in the high chemical sensitivity case-control study.
      CONCLUSIONS: We observed that high chemical sensitive individuals diagnosed by
      using Japanese criteria as MCS patients were more significantly associated with
      SOD2 polymorphisms.

PMID- 23967350
TI  - Aspects of embryonic and larval development in bighead carp Hypophthalmichthys
      nobilis and silver carp Hypophthalmichthys molitrix.
AB  - As bighead carp Hypophthalmichthysnobilis and silver carp H. molitrix (the
      bigheaded carps) are poised to enter the Laurentian Great Lakes and potentially
      damage the region's economically important fishery, information on developmental
      rates and behaviors of carps is critical to assessing their ability to establish
      sustainable populations within the Great Lakes basin. In laboratory experiments,
      the embryonic and larval developmental rates, size, and behaviors of bigheaded
      carp were tracked at two temperature treatments, one "cold" and one "warm".
      Developmental rates were computed using previously described stages of
      development and the cumulative thermal unit method. Both species have similar
      thermal requirements, with a minimum developmental temperature for embryonic
      stages of 12.1 degrees  C for silver carp and 12.9 degrees  C for bighead carp,
      and 13.3 degrees  C for silver carp larval stages and 13.4 degrees  C for bighead
      carp larval stages. Egg size differed among species and temperature treatments,
      as egg size was larger in bighead carp, and "warm" temperature treatments. The
      larvae started robust upwards vertical swimming immediately after hatching,
      interspersed with intervals of sinking. Vertical swimming tubes were used to
      measure water column distribution, and ascent and descent rates of vertically
      swimming fish. Water column distribution and ascent and descent rates changed
      with ontogeny. Water column distribution also showed some diel periodicity.
      Developmental rates, size, and behaviors contribute to the drift distance needed
      to fulfill the early life history requirements of bigheaded carps and can be used
      in conjunction with transport information to assess invasibility of a river. 

PMID- 23967349
TI  - Characterization of GABAergic neurons in the mouse lateral septum: a double
      fluorescence in situ hybridization and immunohistochemical study using tyramide
      signal amplification.
AB  - Gamma-aminobutyric acid (GABA) neurotransmission in the lateral septum (LS) is
      implicated in modulating various behavioral processes, including emotional
      reactivity and maternal behavior. However, identifying the phenotype of GABAergic
      neurons in the CNS has been hampered by the longstanding inability to reliably
      detect somal immunoreactivity for GABA or glutamic acid decarboxylase (GAD), the
      enzyme that produces GABA. In this study, we designed unique probes for both
      GAD65 (GAD2) and GAD67 (GAD1), and used fluorescence in Situ hybridization (FISH)
      with tyramide signal amplification (TSA) to achieve unequivocal detection of cell
      bodies of GABAergic neurons by GAD mRNAs. We quantitatively characterized the
      expression and chemical phenotype of GABAergic neurons across each subdivision of
      LS and in cingulate cortex (Cg) and medial preoptic area (MPOA) in female mice.
      Across LS, almost all GAD65 mRNA-expressing neurons were found to contain GAD67
      mRNA (approximately 95-98%), while a small proportion of GAD67 mRNA-containing
      neurons did not express GAD65 mRNA (5-14%). Using the neuronal marker NeuN,
      almost every neuron in LS (> 90%) was also found to be GABA-positive. Interneuron
      markers using calcium-binding proteins showed that LS GABAergic neurons displayed
      immunoreactivity for calbindin (CB) or calretinin (CR), but not parvalbumin (PV);
      almost all CB- or CR-immunoreactive neurons (98-100%) were GABAergic. The
      proportion of GABAergic neurons immunoreactive for CB or CR varied depending on
      the subdivisions examined, with the highest percentage of colocalization in the
      caudal intermediate LS (LSI) (approximately 58% for CB and 35% for CR). These
      findings suggest that the vast majority of GABAergic neurons within the LS have
      the potential for synthesizing GABA via the dual enzyme systems GAD65 and GAD67,
      and each subtype of GABAergic neurons identified by distinct calcium-binding
      proteins may exert unique roles in the physiological function and neuronal
      circuitry of the LS. 

PMID- 23967351
TI  - Immunogenic and antioxidant effects of a pathogen-associated prenyl pyrophosphate
      in Anopheles gambiae.
AB  - Despite efficient vector transmission, Plasmodium parasites suffer great
      bottlenecks during their developmental stages within Anopheles mosquitoes. The
      outcome depends on a complex three-way interaction between host, parasite and gut
      bacteria. Although considerable progress has been made recently in deciphering
      Anopheles effector responses, little is currently known regarding the underlying
      microbial immune elicitors. An interesting candidate in this sense is the
      pathogen-derived prenyl pyrophosphate and designated phosphoantigen (E)-4-hydroxy
      3-methyl-but-2-enyl pyrophosphate (HMBPP), found in Plasmodium and most
      eubacteria but not in higher eukaryotes. HMBPP is the most potent stimulant known
      of human Vgamma9Vdelta2 T cells, a unique lymphocyte subset that expands during
      several infections including malaria. In this study, we show that Vgamma9Vdelta2
      T cells proliferate when stimulated with supernatants from intraerythrocytic
      stages of Plasmodium falciparum cultures, suggesting that biologically relevant
      doses of phosphoantigens are excreted by the parasite. Next, we used Anopheles
      gambiae to investigate the immune- and redox- stimulating effects of HMBPP. We
      demonstrate a potent activation in vitro of all but one of the signaling pathways
      earlier implicated in the human Vgamma9Vdelta2 T cell response, as p38, JNK and
      PI3K/Akt but not ERK were activated in the A. gambiae 4a3B cell line.
      Additionally, both HMBPP and the downstream endogenous metabolite isopentenyl
      pyrophosphate displayed antioxidant effects by promoting cellular tolerance to
      hydrogen peroxide challenge. When provided in the mosquito blood meal, HMBPP
      induced temporal changes in the expression of several immune genes. In contrast
      to meso-diaminopimelic acid containing peptidoglycan, HMBPP induced expression of
      dual oxidase and nitric oxide synthase, two key determinants of Plasmodium
      infection. Furthermore, temporal fluctuations in midgut bacterial numbers were
      observed. The multifaceted effects observed in this study indicates that HMBPP is
      an important elicitor in common for both Plasmodium and gut bacteria in the
      mosquito. 

PMID- 23967352
TI  - epsilon subunit of Bacillus subtilis F1-ATPase relieves MgADP inhibition.
AB  - MgADP inhibition, which is considered as a part of the regulatory system of ATP
      synthase, is a well-known process common to all F1-ATPases, a soluble component
      of ATP synthase. The entrapment of inhibitory MgADP at catalytic sites terminates
      catalysis. Regulation by the epsilon subunit is a common mechanism among F1
      ATPases from bacteria and plants. The relationship between these two forms of
      regulatory mechanisms is obscure because it is difficult to distinguish which is
      active at a particular moment. Here, using F1-ATPase from Bacillus subtilis
      (BF1), which is strongly affected by MgADP inhibition, we can distinguish MgADP
      inhibition from regulation by the epsilon subunit. The epsilon subunit did not
      inhibit but activated BF1. We conclude that the epsilon subunit relieves BF1 from
      MgADP inhibition. 

PMID- 23967353
TI  - Microtubule-associated type II protein kinase A is important for neurite
      elongation.
AB  - Neuritogenesis is a process through which neurons generate their widespread axon
      and dendrites. The microtubule cytoskeleton plays crucial roles throughout
      neuritogenesis. Our previous study indicated that the amount of type II protein
      kinase A (PKA) on microtubules significantly increased upon neuronal
      differentiation and neuritogenesis. While the overall pool of PKA has been shown
      to participate in various neuronal processes, the function of microtubule
      associated PKA during neuritogenesis remains largely unknown. First, we showed
      that PKA localized to microtubule-based region in different neurons. Since PKA is
      essential for various cellular functions, globally inhibiting PKA activity will
      causes a wide variety of phenotypes in neurons. To examine the function of
      microtubule-associated PKA without changing the total PKA level, we utilized the
      neuron-specific PKA anchoring protein MAP2. Overexpressing the dominant negative
      MAP2 construct that binds to type II PKA but cannot bind to the microtubule
      cytoskeleton in dissociated hippocampal neurons removed PKA from microtubules and
      resulted in compromised neurite elongation. In addition, we demonstrated that the
      association of PKA with microtubules can also enhance cell protrusion using the
      non-neuronal P19 cells. Overexpressing a MAP2 deletion construct which does not
      target PKA to the microtubule cytoskeleton caused non-neuronal cells to generate
      shorter cell protrusions than control cells overexpressing wild-type MAP2 that
      anchors PKA to microtubules. Finally, we demonstrated that the ability of
      microtubule-associated PKA to promote protrusion elongation was independent of
      MAP2 phosphorylation. This suggests other proteins in close proximity to the
      microtubule cytoskeleton are involved in this process. 

PMID- 23967354
TI  - Genetic network and breeding patterns of a sicklefin lemon shark (Negaprion
      acutidens) population in the Society Islands, French Polynesia.
AB  - Human pressures have put many top predator populations at risk of extinction.
      Recent years have seen alarming declines in sharks worldwide, while their
      resilience remains poorly understood. Studying the ecology of small populations
      of marine predators is a priority to better understand their ability to withstand
      anthropogenic and environmental stressors. In the present study, we monitored a
      naturally small island population of 40 adult sicklefin lemon sharks in Moorea,
      French Polynesia over 5 years. We reconstructed the genetic relationships among
      individuals and determined the population's mating system. The genetic network
      illustrates that all individuals, except one, are interconnected at least through
      one first order genetic relationship. While this species developed a clear
      inbreeding avoidance strategy involving dispersal and migration, the small
      population size, low number of breeders, and the fragmented environment
      characterizing these tropical islands, limits its complete effectiveness. 

PMID- 23967355
TI  - Bruton's tyrosine kinase mediates the synergistic signalling between TLR9 and the
      B cell receptor by regulating calcium and calmodulin.
AB  - B cells signal through both the B cell receptor (BCR) which binds antigens and
      Toll-like receptors (TLRs) including TLR9 which recognises CpG DNA. Activation of
      TLR9 synergises with BCR signalling when the BCR and TLR9 co-localise within an
      auto-phagosome-like compartment. Here we report that Bruton's tyrosine kinase
      (BTK) is required for synergistic IL6 production and up-regulation of surface
      expression of MHC-class-II, CD69 and CD86 in primary murine and human B cells. We
      show that BTK is essential for co-localisation of the BCR and TLR9 within a
      potential auto-phagosome-like compartment in the Namalwa human B cell line.
      Downstream of BTK we find that calcium acting via calmodulin is required for this
      process. These data provide new insights into the role of BTK, an important
      target for autoimmune diseases, in B cell activation. 

PMID- 23967356
TI  - The malnutrition-related increase in early visceralization of Leishmania donovani
      is associated with a reduced number of lymph node phagocytes and altered conduit
      system flow.
AB  - In a murine model of moderate childhood malnutrition we found that polynutrient
      deficiency led to a 4-5-fold increase in early visceralization of L. donovani (3
      days post-infection) following cutaneous infection and a 16-fold decrease in
      lymph node barrier function (p<0.04 for all). To begin to understand the
      mechanistic basis for this malnutrition-related parasite dissemination we
      analyzed the cellularity, architecture, and function of the skin-draining lymph
      node. There was no difference in the localization of multiple cell populations in
      the lymph node of polynutrient deficient (PND) mice, but there was reduced
      cellularity with fewer CD11c(+)dendritic cells (DCs), fibroblastic reticular
      cells (FRCs), MOMA-2(+) macrophages, and CD169(+) subcapsular sinus macrophage
      (p<0.05 for all) compared to the well-nourished (WN) mice. The parasites were
      equally co-localized with DCs associated with the lymph node conduit network in
      the WN and PND mice, and were found in the high endothelial venule into which the
      conduits drain. When a fluorescent low molecular weight (10 kD) dextran was
      delivered in the skin, there was greater efflux of the marker from the lymph node
      conduit system to the spleens of PND mice (p<0.04), indicating that flow through
      the conduit system was altered. There was no evidence of disruption of the
      conduit or subcapsular sinus architecture, indicating that the movement of
      parasites into the subcortical conduit region was due to an active process and
      not from passive movement through a leaking barrier. These results indicate that
      the impaired capacity of the lymph node to act as a barrier to dissemination of
      L. donovani infection is associated with a reduced number of lymph node
      phagocytes, which most likely leads to reduced capture of parasites as they
      transit through the sinuses and conduit system. 

PMID- 23967357
TI  - A novel qPCR assay for the detection of African animal trypanosomosis in
      trypanotolerant and trypanosusceptible cattle breeds.
AB  - This study was conducted to (i) determine the prevalence of African Animal
      Trypanosomosis (AAT) in tsetse challenged areas, (ii) compare conventional with
      qPCR detection systems and (iii) evaluate the host genetic background and biology
      as risk factors. AAT prevalence studies are often confronted with low levels of
      parasitaemia. Hence, we designed a novel qPCR assay using primers and species
      specific probes amplifying the Internal Transcribed Spacer 1 (ITS1) gene. Thereby
      all three AAT species could be detected simultaneously. 368 individuals from
      three cattle types (Baoule, Zebu and hybrids) originating from 72 farms in
      Burkina Faso were analysed. Farmers were interviewed and morphometric
      measurements of the cattle taken. A chi-squared test and a logistic regression
      model were calculated to detect associations with infection. In our study, the
      overall rate of prevalence detected with the novel qPCR assay was 11.14%.
      Compared to conventional PCR we identified a concordance of 91.30%. We tested 41
      animals positive for trypanosome DNA, five animals showed multiple infections.
      Zebus were twice as often infected (21.74%) compared to Baoule (9.70%) and
      hybrids (9.57%). Trypanosoma vivax is the dominant species (9.24%), as compared
      to T. congolense (2.44%) and T. brucei (0.82%). The chi-squared tests linking the
      infection events to the breeds (Zebu vs. Baoule and Zebu vs. hybrids) were on the
      border of significance. No significant association with other tested parameters
      could be detected. We introduce a novel qPCR technique for the fast, sensitive
      and simultaneous detection of the three AAT species. Our results suggest that
      associations with breed and infection exist since Zebu cattle are more likely to
      be infected compared to Baoule and hybrids. Indigenous taurine cattle breeds,
      like the Baoule, therefore provide a unique and valuable genetic resource. 

PMID- 23967358
TI  - Multi-gene detection and identification of mosquito-borne RNA viruses using an
      oligonucleotide microarray.
AB  - BACKGROUND: Arthropod-borne viruses are important emerging pathogens world-wide.
      Viruses transmitted by mosquitoes, such as dengue, yellow fever, and Japanese
      encephalitis viruses, infect hundreds of millions of people and animals each
      year. Global surveillance of these viruses in mosquito vectors using molecular
      based assays is critical for prevention and control of the associated diseases.
      Here, we report an oligonucleotide DNA microarray design, termed ArboChip5.1, for
      multi-gene detection and identification of mosquito-borne RNA viruses from the
      genera Flavivirus (family Flaviviridae), Alphavirus (Togaviridae),
      Orthobunyavirus (Bunyaviridae), and Phlebovirus (Bunyaviridae).
      METHODOLOGY/PRINCIPAL FINDINGS: The assay utilizes targeted PCR amplification of
      three genes from each virus genus for electrochemical detection on a portable,
      field-tested microarray platform. Fifty-two viruses propagated in cell-culture
      were used to evaluate the specificity of the PCR primer sets and the ArboChip5.1
      microarray capture probes. The microarray detected all of the tested viruses and
      differentiated between many closely related viruses such as members of the
      dengue, Japanese encephalitis, and Semliki Forest virus clades. Laboratory
      infected mosquitoes were used to simulate field samples and to determine the
      limits of detection. Additionally, we identified dengue virus type 3, Japanese
      encephalitis virus, Tembusu virus, Culex flavivirus, and a Quang Binh-like virus
      from mosquitoes collected in Thailand in 2011 and 2012. CONCLUSIONS/SIGNIFICANCE:
      We demonstrated that the described assay can be utilized in a comprehensive field
      surveillance program by the broad-range amplification and specific identification
      of arboviruses from infected mosquitoes. Furthermore, the microarray platform can
      be deployed in the field and viral RNA extraction to data analysis can occur in
      as little as 12 h. The information derived from the ArboChip5.1 microarray can
      help to establish public health priorities, detect disease outbreaks, and
      evaluate control programs.

PMID- 23967359
TI  - Use of a cholera rapid diagnostic test during a mass vaccination campaign in
      response to an epidemic in Guinea, 2012.
AB  - BACKGROUND: During the 2012 cholera outbreak in the Republic of Guinea, the
      Ministry of Health, supported by Medecins Sans Frontieres - Operational Center
      Geneva, used the oral cholera vaccine Shanchol as a part of the emergency
      response. The rapid diagnostic test (RDT) Crystal VC, widely used during
      outbreaks, detects lipopolysaccharide antigens of Vibrio cholerae O1 and O139,
      both included in Shanchol. In the context of reactive use of a whole-cell cholera
      vaccine in a region where cholera cases have been reported, it is essential to
      know what proportion of vaccinated individuals would be reactive to the RDT and
      for how long after vaccination. METHODOLOGY/PRINCIPAL FINDINGS: A total of 108
      vaccinated individuals, selected systematically among all persons older than one
      year, were included at vaccination sites and 106 were included in the analysis.
      Stools samples of this cohort of vaccinated participants were collected and
      tested with the RDT every day until the test was negative for two consecutive
      visits or for a maximum of 7 days. A total of 94.3% of cholera vaccine recipients
      had a positive test after vaccination; all except one of these positive results
      were reactive only with the O139 antigen. The mean time to become negative in
      those with an initial positive result after vaccination was 3.8 days, standard
      deviation 1.1 days. CONCLUSIONS/SIGNIFICANCE: The RDT Crystal VC becomes positive
      in persons recently vaccinated against cholera, although almost exclusively to
      the O139 antigen. This reactivity largely disappeared within five days after
      vaccination. These results suggest that the test can be used normally as soon as
      24 hours after vaccination in a context of O1 epidemics, which represent the vast
      majority of cases, and after a period of five days in areas where V. cholerae
      O139 is present. The reason why only O139 test line became positive remains to be
      investigated.

PMID- 23967361
TI  - Cholera in pregnancy: outcomes from a specialized cholera treatment unit for
      pregnant women in Leogane, Haiti.
AB  - BACKGROUND: The association between cholera in pregnancy and negative fetal
      outcome has been described since the 19(th) century. However, there is limited
      published literature on the subject. We describe pregnancy outcomes from a
      specialized multidisciplinary hospital unit at the onset of a large cholera
      outbreak in Haiti in 2010 and 2011. METHODS: Pregnant women with cholera were
      hospitalized in a specialized unit within the MSF hospital compound in Leogane
      and treated using standard cholera treatment guidelines but with earlier, more
      intense fluid replacement. All women had intravenous access established at
      admission regardless of their hydration status, and all received antibiotic
      treatment. Data were collected on patient demographics, pregnancy and cholera
      status, and pregnancy outcome. In this analysis we calculated risk ratios for
      fetal death and performed logistic regression analysis to control for confounding
      factors. RESULTS: 263 pregnant women with cholera were hospitalized between
      December 2010 and July 2011. None died during hospitalization, 226 (86%) were
      discharged with a preserved pregnancy and 16 (6%) had live fullterm singleton
      births, of whom 2 died within the first 5 days postpartum. The remaining 21
      pregnancies (8%) resulted in intrauterine fetal death. The risk of fetal death
      was associated with factors reflecting severity of the cholera episode: after
      adjusting for confounding factors, the strongest risk factor for fetal death was
      severe maternal dehydration (adjusted risk ratio for severe vs. mild dehydration
      was 9.4, 95% CI 2.5-35.3, p = 0.005), followed by severe vomiting (adjusted risk
      ratio 5.1, 95% 1.1-23.8, p = 0.041). CONCLUSION: This is the largest cohort of
      pregnant women with cholera described to date. The main risk factor identified
      for fetal death was severity of dehydration. Our experience suggests that
      establishing specialized multidisciplinary units which facilitate close follow-up
      of both pregnancy and dehydration status due to cholera could be beneficial for
      patients, especially in large epidemics.

PMID- 23967360
TI  - Benznidazole and posaconazole in experimental Chagas disease: positive
      interaction in concomitant and sequential treatments.
AB  - BACKGROUND: Current chemotherapy for Chagas disease is unsatisfactory due to its
      limited efficacy, particularly in the chronic phase, with frequent side effects
      that can lead to treatment discontinuation. Combined therapy is envisioned as an
      ideal approach since it may improve treatment efficacy whilst decreasing toxicity
      and the likelihood of resistance development. We evaluated the efficacy of
      posaconazole in combination with benznidazole on Trypanosoma cruzi infection in
      vivo. METHODS AND FINDINGS: Benznidazole and posaconazole were administered
      individually or in combination in an experimental acute murine infection model.
      Using a rapid treatment protocol for 7 days, the combined treatments were more
      efficacious in reducing parasitemia levels than the drugs given alone, with the
      effects most evident in combinations of sub-optimal doses of the drugs.
      Subsequently, the curative action of these drug combinations was investigated,
      using the same infection model and 25, 50, 75 or 100 mg/kg/day (mpk) of
      benznidazole in combination with 5, 10 or 20 mpk of posaconazole, given alone or
      concomitantly for 20 days. The effects of the combination treatments on
      parasitological cures were higher than the sum of such effects when the drugs
      were administered separately at the same doses, indicating synergistic activity.
      Finally, sequential therapy experiments were carried out with benznidazole or
      posaconazole over a short interval (10 days), followed by the second drug
      administered for the same period of time. It was found that the sequence of
      benznidazole (100 mpk) followed by posaconazole (20 mpk) provided cure rates
      comparable to those obtained with the full (20 days) treatments with either drug
      alone, and no cure was observed for the short treatments with drugs given alone.
      CONCLUSIONS: Our data demonstrate the importance of investigating the potential
      beneficial effects of combination treatments with marketed compounds, and showed
      that combinations of benznidazole with posaconazole have a positive interaction
      in murine models of Chagas disease.

PMID- 23967362
TI  - Serum metabolome and lipidome changes in adult patients with primary dengue
      infection.
AB  - BACKGROUND: Dengue virus (DENV) is the most widespread arbovirus with an
      estimated 100 million infections occurring every year. Endemic in the tropical
      and subtropical areas of the world, dengue fever/dengue hemorrhagic fever
      (DF/DHF) is emerging as a major public health concern. The complex array of
      concurrent host physiologic changes has hampered a complete understanding of
      underlying molecular mechanisms of dengue pathogenesis. METHODOLOGY/PRINCIPLE
      FINDINGS: Systems level characterization of serum metabolome and lipidome of
      adult DF patients at early febrile, defervescence, and convalescent stages of
      DENV infection was performed using liquid chromatography- and gas chromatography
      mass spectrometry. The tractability of following metabolite and lipid changes in
      a relatively large sample size (n = 44) across three prominent infection stages
      allowed the identification of critical physiologic changes that coincided with
      the different stages. Sixty differential metabolites were identified in our
      metabolomics analysis and the main metabolite classes were free fatty acids,
      acylcarnitines, phospholipids, and amino acids. Major perturbed metabolic
      pathways included fatty acid biosynthesis and beta-oxidation, phospholipid
      catabolism, steroid hormone pathway, etc., suggesting the multifactorial nature
      of human host responses. Analysis of phospholipids and sphingolipids verified the
      temporal trends and revealed association with lymphocytes and platelets numbers.
      These metabolites were significantly perturbed during the early stages, and
      normalized to control levels at convalescent stage, suggesting their potential
      utility as prognostic markers. CONCLUSIONS/SIGNIFICANCE: DENV infection causes
      temporally distinct serum metabolome and lipidome changes, and many of the
      differential metabolites are involved in acute inflammatory responses. Our global
      analyses revealed early anti-inflammatory responses working in concert to
      modulate early pro-inflammatory processes, thus preventing the host from
      development of pathologies by excessive or prolonged inflammation. This study is
      the first example of how an omic- approach can divulge the extensive, concurrent,
      and dynamic host responses elicited by DENV and offers plausible physiological
      insights to why DF is self limiting.

PMID- 23967363
TI  - Evaluating paratransgenesis as a potential control strategy for African
      trypanosomiasis.
AB  - Genetic-modification strategies are currently being developed to reduce the
      transmission of vector-borne diseases, including African trypanosomiasis. For
      tsetse, the vector of African trypanosomiasis, a paratransgenic strategy is being
      considered: this approach involves modification of the commensal symbiotic
      bacteria Sodalis to express trypanosome-resistance-conferring products. Modified
      Sodalis can then be driven into the tsetse population by cytoplasmic
      incompatibility (CI) from Wolbachia bacteria. To evaluate the effectiveness of
      this paratransgenic strategy in controlling African trypanosomiasis, we developed
      a three-species mathematical model of trypanosomiasis transmission among tsetse,
      humans, and animal reservoir hosts. Using empirical estimates of CI parameters,
      we found that paratransgenic tsetse have the potential to eliminate
      trypanosomiasis, provided that any extra mortality caused by Wolbachia
      colonization is low, that the paratransgene is effective at protecting against
      trypanosome transmission, and that the target tsetse species comprises a large
      majority of the tsetse population in the release location. 

PMID- 23967364
TI  - Schistosoma mansoni-mediated suppression of allergic airway inflammation requires
      patency and Foxp3+ Treg cells.
AB  - The continual rise of asthma in industrialised countries stands in strong
      contrast to the situation in developing lands. According to the modified Hygiene
      Hypothesis, helminths play a major role in suppressing bystander immune responses
      to allergens, and both epidemiological and experimental studies suggest that the
      tropical parasitic trematode Schistosoma mansoni elicits such effects. The focus
      of this study was to investigate which developmental stages of schistosome
      infection confer suppression of allergic airway inflammation (AAI) using
      ovalbumin (OVA) as a model allergen. Moreover, we assessed the functional role
      and localization of infection-induced CD4(+)Foxp3(+) regulatory T cells (Treg) in
      mediating such suppressive effects. Therefore, AAI was elicited using
      OVA/adjuvant sensitizations with subsequent OVA aerosolic challenge and was
      induced during various stages of infection, as well as after successful anti
      helminthic treatment with praziquantel. The role of Treg was determined by
      specifically depleting Treg in a genetically modified mouse model (DEREG) during
      schistosome infection. Alterations in AAI were determined by cell infiltration
      levels into the bronchial system, OVA-specific IgE and Th2 type responses, airway
      hyper-sensitivity and lung pathology. Our results demonstrate that schistosome
      infection leads to a suppression of OVA-induced AAI when mice are challenged
      during the patent phase of infection: production of eggs by fecund female worms.
      Moreover, this ameliorating effect does not persist after anti-helminthic
      treatment, and depletion of Treg reverts suppression, resulting in aggravated AAI
      responses. This is most likely due to a delayed reconstitution of Treg in
      infected-depleted animals which have strong ongoing immune responses. In summary,
      we conclude that schistosome-mediated suppression of AAI requires the presence of
      viable eggs and infection-driven Treg cells. These data provide evidence that
      helminth derived products could be incorporated into treatment strategies that
      specifically target suppression of immune responses in AAI by inducing Treg
      cells. 

PMID- 23967365
TI  - Helminthic infections rates and malaria in HIV-infected pregnant women on anti
      retroviral therapy in Rwanda.
AB  - BACKGROUND: Within sub-Saharan Africa, helminth and malaria infections cause
      considerable morbidity in HIV-positive pregnant women and their offspring.
      Helminth infections are also associated with a higher risk of mother-to-child HIV
      transmission. The aim of this study was to determine the prevalence of, and the
      protective and risk factors for helminth and malaria infections in pregnant HIV
      positive Rwandan women receiving anti-retroviral therapy (ART). METHODOLOGY AND
      PRINCIPLE FINDINGS: Pregnant females (n = 980) were recruited from health centres
      in rural and peri-urban locations in the central and eastern provinces of Rwanda.
      Helminth infection was diagnosed using the Kato Katz method whilst the presence
      of Plasmodium falciparum was identified from blood smears. The prevalence of
      helminth infections was 34.3%; of malaria 13.3%, and of co-infections 6.6%.
      Helminth infections were more common in rural (43.1%) than peri-urban (18.0%;
      p<0.0005) sites. A CD4 count <= 350 cells/mm(3) was associated with a higher risk
      of helminth infections (odds ratio, 3.39; 95% CIs, 2.16-5.33; p<0.0005) and
      malaria (3.37 [2.11-5.38]; p<0.0005) whilst helminth infection was a risk factor
      for malaria infection and vice versa. Education and employment reduced the risk
      of all types of infection whilst hand washing protected against helminth
      infection (0.29 [0.19-0.46]; p<0.0005);). The TDF-3TC-NVP (3.47 [2.21-5.45];
      p<0.0005), D4T-3TC-NVP (2.47 [1.27-4.80]; p<0.05) and AZT-NVP (2.60 [1.33-5.08];
      p<0.05) regimens each yielded higher helminth infection rates than the AZT-3TC
      NVP regimen. Anti-retroviral therapy had no effect on the risk of malaria.
      CONCLUSION/SIGNIFICANCE: HIV-positive pregnant women would benefit from the
      scaling up of de-worming programs alongside health education and hygiene
      interventions. The differential effect of certain ART combinations (as observed
      here most strongly with AZT-3TC-NVP) possibly protecting against helminth
      infection warrants further investigation.

PMID- 23967367
TI  - Triple plane dissection in open primary rhinoplasty in middle eastern noses.
AB  - OBJECTIVE: Rhinoplasty started as a closed technique and then the open technique
      gained popularity. Open technique gave surgeons the opportunity to visualize and
      manipulate the cartilaginous skeleton at the tip of the nose precisely. The
      dissection planes in open rhinoplasty technique may be subcutaneous, submuscular
      (under the superficial musculoaponeurotic system), or subpericondrial
      subperiosteal. Each plane has advantages and disadvantages. The aim of this study
      was to combine planes to get the maximal benefit of each plane. METHOD: The study
      was performed on 38 Middle Eastern patients, among whom 23 were females and 15
      were males. All patients presented for primary rhinoplasty. They were divided
      into 5 groups on the basis of their skin thickness. Dissection started
      subcutaneous at the area of the lower lateral cartilages and then shifted
      subsuperficial musculoaponeurotic system over the upper lateral cartilages and
      ended subperiosteal over the bony skeleton. RESULTS: This triple plane of
      dissection gave acceptable results without any complication. Subcutaneous
      dissection allowed thinning of the thick sebaceous skin at the tip and alar
      region, subsuperficial musculoaponeurotic system dissection allowed direct
      exposure of the upper lateral cartilage without thinning skin at an area where it
      is thin, and subperiosteal dissection helped masking any bony irregularities
      resulted from osteotomies. CONCLUSION: The triple plane dissection in open
      primary rhinoplasty in Middle Eastern patients maximized the advantages of each
      plane and minimized the disadvantages and resulted in safe cosmetic results.

PMID- 23967366
TI  - Metabonomics reveals drastic changes in anti-inflammatory/pro-resolving
      polyunsaturated fatty acids-derived lipid mediators in leprosy disease.
AB  - Despite considerable efforts over the last decades, our understanding of leprosy
      pathogenesis remains limited. The complex interplay between pathogens and hosts
      has profound effects on host metabolism. To explore the metabolic perturbations
      associated with leprosy, we analyzed the serum metabolome of leprosy patients.
      Samples collected from lepromatous and tuberculoid patients before and
      immediately after the conclusion of multidrug therapy (MDT) were subjected to
      high-throughput metabolic profiling. Our results show marked metabolic
      alterations during leprosy that subside at the conclusion of MDT. Pathways
      showing the highest modulation were related to polyunsaturated fatty acid (PUFA)
      metabolism, with emphasis on anti-inflammatory, pro-resolving omega-3 fatty
      acids. These results were confirmed by eicosanoid measurements through enzyme
      linked immunoassays. Corroborating the repertoire of metabolites altered in sera,
      metabonomic analysis of skin specimens revealed alterations in the levels of
      lipids derived from lipase activity, including PUFAs, suggesting a high lipid
      turnover in highly-infected lesions. Our data suggest that omega-6 and omega-3,
      PUFA-derived, pro-resolving lipid mediators contribute to reduced tissue damage
      irrespectively of pathogen burden during leprosy disease. Our results demonstrate
      the utility of a comprehensive metabonomic approach for identifying potential
      contributors to disease pathology that may facilitate the development of more
      targeted treatments for leprosy and other inflammatory diseases. 

PMID- 23967368
TI  - CASE REPORT Penetrating Injury of the Orbit by a Needlefish.
AB  - OBJECTIVE: We present a very rare case of penetrating injury into the orbit by a
      needlefish. The patient underwent extirpation twice at another hospital. METHODS:
      We performed foreign body removal from a right subbrow incision under general
      anesthesia. RESULTS: The foreign body was successfully removed and the patient's
      diplopia recovered gradually after surgery. CONCLUSIONS: Treatment was similar to
      that used for penetrating injury. As there is a risk of secondary infection, it
      is important to completely remove the fish body, followed by vigorous irrigation
      and debridement.

PMID- 23967369
TI  - Medical students' perception of the educational environment in a medical college
      in India: a cross-sectional study using the Dundee Ready Education Environment
      questionnaire.
AB  - PURPOSE: The objective of this study was to assess student perceptions of the
      environment in this medical college using the Dundee Ready Educational
      Environment Measure (DREEM). METHODS: Cross-sectional study; 348 medical student
      volunteers (68.1%) of all semesters participated (511 enrolled). DREEM has 50
      items, each rated from 0-4 (Likert scale: 0, strongly disagree to 4, strongly
      agree), that measure five domains: students' perceptions of learning; perceptions
      of teachers; academic self-perception; perceptions of the atmosphere; and social
      self-perception. Mean item scores, domain scores, and global scores were
      computed. RESULTS: The three highest rated items were knowledgeable teachers,
      having good friends, and confidence about passing; the three most problematic
      items were a poor support system for stressed students, inability to memorize
      everything, and over-emphasis on factual learning. The percentage score for
      perception of learning (47.26+/- 14.85) was significantly lower than that for
      teachers (52.28+/- 9.91; P< 0.001); academic self-perception (52.14 +/- 15.21; P
      < 0.001); perception of the atmosphere (51.21 +/- 13.60; P = 0.001); and social
      self-perception (50.63+/- 13.90; P= 0.010). The global scores were lowest for
      eighth-semester students (89.8+/- 21.24) when compared to second (101.33+/-
      21.05; P= 0.003), fourth (107.69+/- 18.96; P< 0.001), and sixth (100.07+/- 20.61;
      P= 0.020). CONCLUSION: Improvement is required across all domains of the
      educational environment at this institution. Students, particularly of the eighth
      semester, perceived the teaching negatively. The lowest scores were given to the
      support system, burdensome course content, and factual learning; thus, a hybrid
      curriculum that includes problem-based learning might provide students with
      stimulating learning; structured clinical teaching with specific curricular
      objectives, as well as mentoring of senior students by faculty and near-peers,
      might improve the learning environment for senior students.

PMID- 23967370
TI  - Attitude and practice of dental surgeons towards pharmaceutical companies'
      marketing gifts.
AB  - Interaction of pharmaceutical companies (PC) with healthcare services has been a
      reason for concern. In medicine, awareness of the ethical implications of these
      interactions have been emphasized upon, while this issue has not been highlighted
      in dentistry. This study undertook a cross-sectional rapid assessment procedure
      to gather views of dentists in various institutions towards unethical practices
      in health care and pharmaceutical industry. The purpose of this study was to
      assess the need for the formulation and implementation of guidelines for the
      interaction of dentists with the pharmaceutical and device industry in the best
      interest of patients. A group of 209 dentists of Lahore including faculty
      members, demonstrators, private practitioners and fresh graduates responded to a
      questionnaire to assess their attitudes and practices towards pharmaceutical
      companies' marketing gifts. The study was conducted during 2011 and provided
      interesting data that showed the pharmaceutical industry is approaching private
      practitioners more frequently than academicians and fresh graduates. Private
      practioners accepted the gifts but mostly recognized them as unethical (over
      65%). Both groups considered sponsoring of on-campus lectures as acceptable (over
      70%). Respondents are not fully aware of the ethical demands which are imperative
      for all health care industries, and there is a dire need of strict guidelines and
      code of ethics for the dentist's interaction with the pharmaceutical and device
      industry so that patient interest is protected. 

PMID- 23967371
TI  - Effect of education based on the "4A Model" on the Iranian nurses' moral distress
      in CCU wards.
AB  - Complexity of health care has caused ethical dilemmas and moral distress to be
      quite unavoidable for nurses. Moral distress is a major, highly prevalent problem
      in the nursing profession. The study aims to investigate the effect of education
      based on the "4A model" on the rate of moral distress among the nurses working in
      Cardiac Care Units (CCU). The participants consisted of 60 nurses working in
      Cardiac Care Units (CCU), 30 in the control and 30 in the intervention group.
      Those in the intervention group took part in the educational workshop about
      "moral distress" and "4A model". The moral distress questionnaire was completed
      by both study groups 1 and 2 months after the intervention. After the
      intervention, the results of repeated measures analysis of variance revealed a
      significant difference in the moral distress mean scores between the intervention
      and the control groups (P<0.001) and within the two groups (P<0.001). Moreover, a
      significant difference was found between the two study groups regarding the mean
      score of moral distress 1 and 2 months after the intervention. The findings of
      the current study revealed a decreasing trend in the moral distress mean score in
      the intervention group, while there was an increasing trend in the control group
      after the intervention. It can be concluded that the "4A model" can be used for
      reducing moral distress and educational interventions can reduce the rate of
      moral distress among nurses. Authors of this study recommend that more studies
      with larger sample sizes be conducted in different hospital wards as well. 

PMID- 23967372
TI  - Brief report: The Third Annual Medical Ethics Congress in Iran.

PMID- 23967374
TI  - How much vitamin D is required to prevent fractures?

PMID- 23967373
TI  - Synthesis and biological evaluation of novel ferrocenyl curcuminoid derivatives.
AB  - With the purpose to improve the biological activities of curcumin, eight novel
      ferrocenyl curcuminoids were synthesized by covalent anchorage of three different
      ferrocenyl ligands. We evaluated their cytotoxicity on B16 melanoma cells and
      normal NIH 3T3 cells, their inhibition of tubulin polymerization and their effect
      on the morphology of endothelial cells. The presence of a ferrocenyl side chain
      was clearly shown to improve the biological activity of most of their
      corresponding organic curcuminoid analogues.

PMID- 23967376
TI  - Insulin-like growth factor 1 is a key regulator of bone mass.

PMID- 23967375
TI  - Clopidogrel (Plavix) could have a negative effect on bone health.

PMID- 23967377
TI  - Loss of wnt/beta-catenin signaling leads to an osteoblast to adipocyte shift.

PMID- 23967378
TI  - AAV-mediated gene therapy for heart failure: enhancing contractility and calcium
      handling.
AB  - Heart failure is a progressive, debilitating disease that is characterized by
      inadequate contractility of the heart. With an aging population, the incidence
      and economic burden of managing heart failure are anticipated to increase
      substantially. Drugs for heart failure only slow its progression and offer no
      cure. However, results of recent clinical trials using recombinant adeno
      associated virus (AAV) gene delivery offer the promise, for the first time, that
      heart failure can be reversed. The strategy is to improve contractility of
      cardiac muscle cells by enhancing their ability to store calcium through
      increased expression of the sarco(endo)plasmic reticulum Ca(2+)-ATPase pump
      (SERCA2a). Preclinical trials have also identified other proteins involved in
      calcium cycling in cardiac muscle that are promising targets for gene therapy in
      heart failure, including the following: protein phosphatase 1, adenylyl cyclase
      6, G-protein-coupled receptor kinase 2, phospholamban, SUMO1, and S100A1. These
      preclinical and clinical trials represent a "quiet revolution" that may end up
      being one of the most significant and remarkable breakthroughs in modern medical
      practice. Of course, a number of uncertainties remain, including the long-term
      utility and wisdom of improving the contractile performance of "sick" muscle
      cells. In this regard, gene therapy may turn out to be a way of buying additional
      time for actual cardiac regeneration to occur using cardiac stem cells or induced
      pluripotent stem cells. 

PMID- 23967380
TI  - HIV and innate immunity - a genomics perspective.
AB  - Innate immunity is a theme of increasing interest for HIV research. However, the
      term is overstretched to cover biological barriers, cellular systems, soluble
      factors, signaling pathways, and effectors and is inconsistently applied. A
      clearer semantic classification of the components of innate immunity is needed,
      which will have direct relevance to the interpretation of human genome variation.
      Here, we discuss genomic approaches that can assist in re-defining the perimeter
      of innate immunity. We place particular emphasis on the characteristics of
      effectors of the intracellular defense against HIV and other pathogens. 

PMID- 23967379
TI  - Gasotransmitters, poisons, and antimicrobials: it's a gas, gas, gas!
AB  - We review recent examples of the burgeoning literature on three gases that have
      major impacts in biology and microbiology. NO, CO and H2S are now co-classified
      as endogenous gasotransmitters with profound effects on mammalian physiology and,
      potentially, major implications in therapeutic applications. All are well known
      to be toxic yet, at tiny concentrations in human and cell biology, play key
      signalling and regulatory functions. All may also be endogenously generated in
      microbes. NO and H2S share the property of being biochemically detoxified, yet
      are beneficial in resisting the bactericidal properties of antibiotics. The
      mechanism underlying this protection is currently under debate. CO, in contrast,
      is not readily removed; mounting evidence shows that CO, and especially organic
      donor compounds that release the gas in biological environments, are themselves
      effective, novel antimicrobial agents. 

PMID- 23967381
TI  - Novel methods for studying multiprotein complexes in vivo.
AB  - The current consensus is that the majority of proteins act in concert in the
      cell, as homo- and heteromeric complexes of two or more proteins that carry out
      discrete biological functions. A wide range of genomic, proteomic, biochemical,
      structural and biophotonic techniques have been employed over the years to study
      the protein-protein interactions that define complexes, with the end goal of
      producing a spatiotemporal map of these modular functional units throughout the
      cell. Recent advances in the analysis of in vivo complexes have greatly improved
      structural, functional and temporal resolution, and this review highlights novel
      approaches ranging from proximity-dependent labeling and cross-linking/mass
      spectrometry through pulse-chase epitope labeling and targeted protein
      degradation. 

PMID- 23967382
TI  - Recent advances in valvular heart disease.
AB  - Valvular heart disease is one of the most dynamic and exciting fields in
      cardiovascular medicine, with significant developments in investigation and
      management over recent years. In this review, we cover some of the most exciting
      areas, including the potential for treatment strategies aimed at halting the
      progression of early aortic stenosis, the use of positron emission tomography in
      assessing disease activity, novel percutaneous strategies for treating valve
      disease and new directions in the prevention and management of infective
      endocarditis. 

PMID- 23967383
TI  - Screening colonoscopy: should we focus more on technique and less on technology?
AB  - Several large studies have confirmed that high quality colonoscopic surveillance
      can improve outcomes with substantial reduction in colorectal cancer rates. In
      order to improve outcomes from screening colonoscopy and help detect adenomas,
      the emphasis has been mainly on improvements in technology like high-resolution
      scopes, computerized as well as dye-based chromoendoscopy and wide-angle
      endoscopes. In addition to the equipment and technological innovation in the
      equipment used, a number of other factors like experience of the endoscopist,
      optimal withdrawal techniques, position changes during colonoscopy and bowel
      preparation can all influence adenoma detection and thereby the quality of
      colonoscopic surveillance. In this review we will focus on recent studies
      investigating these aspects of colonoscopy and their impact on adenoma or polyp
      detection. 

PMID- 23967384
TI  - Reproducibility in the automated quantitative assessment of HER2/neu for breast
      cancer.
AB  - BACKGROUND: With the emerging role of digital imaging in pathology and the
      application of automated image-based algorithms to a number of quantitative
      tasks, there is a need to examine factors that may affect the reproducibility of
      results. These factors include the imaging properties of whole slide imaging
      (WSI) systems and their effect on the performance of quantitative tools. This
      manuscript examines inter-scanner and inter-algorithm variability in the
      assessment of the commonly used HER2/neu tissue-based biomarker for breast cancer
      with emphasis on the effect of algorithm training. MATERIALS AND METHODS: A total
      of 241 regions of interest from 64 breast cancer tissue glass slides were scanned
      using three different whole-slide images and were analyzed using two different
      automated image analysis algorithms, one with preset parameters and another
      incorporating a procedure for objective parameter optimization. Ground truth from
      a panel of seven pathologists was available from a previous study. Agreement
      analysis was used to compare the resulting HER2/neu scores. RESULTS: The results
      of our study showed that inter-scanner agreement in the assessment of HER2/neu
      for breast cancer in selected fields of view when analyzed with any of the two
      algorithms examined in this study was equal or better than the inter-observer
      agreement previously reported on the same set of data. Results also showed that
      discrepancies observed between algorithm results on data from different scanners
      were significantly reduced when the alternative algorithm that incorporated an
      objective re-training procedure was used, compared to the commercial algorithm
      with preset parameters. CONCLUSION: Our study supports the use of objective
      procedures for algorithm training to account for differences in image properties
      between WSI systems.

PMID- 23967385
TI  - Automated extraction of precise protein expression patterns in lymphoma by text
      mining abstracts of immunohistochemical studies.
AB  - BACKGROUND: In general, surgical pathology reviews report protein expression by
      tumors in a semi-quantitative manner, that is, -, -/+, +/-, +. At the same time,
      the experimental pathology literature provides multiple examples of precise
      expression levels determined by immunohistochemical (IHC) tissue examination of
      populations of tumors. Natural language processing (NLP) techniques enable the
      automated extraction of such information through text mining. We propose
      establishing a database linking quantitative protein expression levels with
      specific tumor classifications through NLP. MATERIALS AND METHODS: Our method
      takes advantage of typical forms of representing experimental findings in terms
      of percentages of protein expression manifest by the tumor population under
      study. Characteristically, percentages are represented straightforwardly with the
      % symbol or as the number of positive findings of the total population. Such text
      is readily recognized using regular expressions and templates permitting
      extraction of sentences containing these forms for further analysis using
      grammatical structures and rule-based algorithms. RESULTS: Our pilot study is
      limited to the extraction of such information related to lymphomas. We achieved a
      satisfactory level of retrieval as reflected in scores of 69.91% precision and
      57.25% recall with an F-score of 62.95%. In addition, we demonstrate the utility
      of a web-based curation tool for confirming and correcting our findings.
      CONCLUSIONS: The experimental pathology literature represents a rich source of
      pathobiological information, which has been relatively underutilized. There has
      been a combinatorial explosion of knowledge within the pathology domain as
      represented by increasing numbers of immunophenotypes and disease
      subclassifications. NLP techniques support practical text mining techniques for
      extracting this knowledge and organizing it in forms appropriate for pathology
      decision support systems.

PMID- 23967386
TI  - What is new in the evaluation of diagnostic digital cytopathology in
      cervicovaginal smears?

PMID- 23967388
TI  - Bacteriology swabs in primary total knee arthroplasty.
AB  - OBJECTIVE: An early detection of possible periprosthetic infection may lead to an
      earlier and potentially less invasive treatment of infected total knee
      arthroplasty TKA). The purpose of the present study was to evaluate
      retrospectively our current, affordable clinical practice of intra-operative swab
      taking during primary TKA. METHODS: A total of 206 primary TKA were analysed
      retrospectively for intra-operative bacteriology swabs and subsequent
      periprosthetic infection. All bacteriology swabs were obtained in a standardized
      manner including a tissue sample. Data was statistically evaluated concerning
      standard descriptive statistics and using the chi-square test. RESULTS: Bacteria
      were identified in 43.4% with coagulase-negative staphylococci being the most
      frequently isolated pathogens (52.2%). Regarding the contingency tables and chi
      squared tests, generally no association was found between positive intra
      operative swabs and subsequent periprosthetic infection as well as all other
      parameters investigated (timing of the antibiotic prophylaxis and pre-operative
      laboratory results). CONCLUSIONS: Bacteriology swabs during primary total knee
      arthroplasty are no adequate measure to predict subsequent periprosthetic
      infections, even if augmented with a tissue sample.

PMID- 23967387
TI  - In vitro efficacy of cold atmospheric pressure plasma on S. sanguinis biofilms in
      comparison of two test models.
AB  - Dental plaque critically affects the etiology of caries, periodontitis and
      periimplantitis. The mechanical removal of plaque can only be performed partially
      due to limited accessibility. Therefore, plaque still represents one of the major
      therapeutic challenges. Even though antiseptic mouth rinses reduce the extent of
      biofilm temporarily, plaque removal remains incomplete and continuous usage can
      even result in side effects. Here we tested argon plasma produced by kinpen09 as
      one option to inactivate microorganisms and to eliminate plaque. S. sanguinis
      biofilms cultivated in either the European Biofilm Reactor (EUREBI) or in 24 well
      plates were treated with argon plasma. In both test systems a homogeneous, good
      analyzable and stable biofilm was produced on the surface of titan plates within
      72 h (>6,9 log10 CFU/ml). Despite the significantly more powerful biofilm
      production in EUREBI, the difference of 0.4 log10 CFU/ml between EUREBI and the
      24 well plates was practically not relevant. For that reason both test models
      were equally qualified for the analysis of efficacy of cold atmospheric pressure
      plasma. We demonstrate a significant reduction of the biofilm compared to the
      control in both test models. After plasma application of 180 s the biofilm
      produced in EUREBI or in 24 well plates was decreased by 0.6 log10 CFU/ml or 0.5
      log10 CFU/ml, respectively. In comparison to recently published studies analyzing
      the efficacy of kinpen09, S. sanguinis produces a hardly removable biofilm.
      Future investigations using reduced distances between plasma source and biofilm,
      various compositions of plasma and alternative plasma sources will contribute to
      further optimization of the efficacy against S. sanguinis biofilms. 

PMID- 23967389
TI  - Detection of the intercellular adhesion gene cluster (ica) in clinical
      Staphylococcus aureus isolates.
AB  - Staphylococcus aureus is a major hospital and community pathogen having the
      aptitude to cause a wide variety of infections in men. The ability of
      microorganisms to produce biofilm facilitates them to withstand the host immune
      response and is recognized as one factor contributing to chronic or persistent
      infections. It was demonstrated that the ica-encoded genes lead to the
      biosynthesis of polysaccharide intercellular adhesion (PIA) molecules, and may be
      involved in the accumulation phase of biofilm formation. Different studies have
      shown the decisive role of the ica gene as virulence factors in staphylococcal
      infections. This study was carried out to demonstrate the relationship between
      ica gene and production of slime layer in S. aureus strains. Sixty S. aureus
      strains were isolated from patients. The isolates were identified morphologically
      and biochemically following standard laboratory methods. After identification,
      the staphylococcal isolates were maintained in trypticase soy broth (TSB), to
      which 15% glycerol was added, and stored at -20 degrees C. Slime formation and
      biofilm assay was monitored. A PCR assay was developed to identify the presence
      of icaD (intercellular adhesion gene) gene in all isolates. Thirty-nine slime
      producing colonies with CRA plates (65%) formed black colors, the remaining 21
      isolates were pink (35%). In the quantitative biofilm assay 35 (58%) produced
      biofilm while 25 (42%) isolates did not exhibit this property. All isolates were
      positive for detection of icaD gene by PCR method. The interaction of icaA and
      icaD in the investigated isolates may be important in slime layer formation and
      biofilm phenomena. We propose PCR detection of the ica gene locus as a rapid and
      effective method to be used for discrimination between potentially virulent and
      nonvirulent isolates, with implications for therapeutic and preventive measures
      pertainin to the management of colonized indwelling catheters. 

PMID- 23967390
TI  - High resistance of Pseudomonas aeruginosa to paromomycin, an agent used for
      selective bowel decontamination (SBD).
AB  - BACKGROUND: Paromomycin is used for selective bowel decontamination (SBD) in
      patients undergoing bone marrow transplantation in many hospitals, but there are
      no published resistance data for this compound in the recent medical literature.
      The aim of this study was to investigate the in vitro activity of paromomycin
      against the common intestinal bacteria E. coli and P. aeruginosa. METHODS: 94 E.
      coli isolates and 77 P. aeruginosa isolates derived from clinical specimens were
      tested by broth microdilution against paromomycin and amikacin, respectively,
      following the CLSI recommendations for testing amikacin. RESULTS: 86 of 94 E.
      coli isolates (91%) and 71 of 77 P. aeruginosa isolates (92%) showed in vitro
      susceptibility to amikacin (MIC90 for both compounds: 16 ug/ml, range: 1-32 ug/ml
      for E. coli and 1->128 ug/ml for P. aeruginosa). Paromomycin was active against
      83/94 E. coli isolates (88%; MIC90: 32 ug/ml, range: 2->128 ug/ml), but showed
      poor in vitro activity against P. aeruginosa (3/77 isolates susceptible [4%];
      MIC90: >128 ug/ml, range: 2->128 ug/ml). CONCLUSION: If SBD with inclusion of an
      aminoglycoside antibiotic is applied, paromomycin should not be used unless local
      resistance data provide evidence of a sufficient in vitro activity of this
      compound against P. aeruginosa.

PMID- 23967391
TI  - Silver nanoparticles as active ingredient used for alcohol-free mouthwash.
AB  - We developed an effective and non-irritant mouthwash that is alcohol-free and has
      a low concentration of silver nanoparticles (SNP) in order to be used for
      preventing oral cavity infections in immunocompromised oncologic patients. We
      studied antimicrobial effects of silver nanoparticles (SNP) in the range of (50
      0.024 ug/ml) and 3% of ethanol (30,000 ug/ml) in mouthwash. Antimicrobial effects
      of two treatments were studied by doing challenge test on microorganisms such as
      Streptococcus mutans, Staphylococcus aureus, Escherichia coli, Pseudomonas
      aeruginosa, Candida albicans and measuring MIC and MBC (MFC) values of SNP toward
      mentioned microorganisms. These values of SNP respectively were in the range of
      (0.78-3.12) and (1.56-12.5 ug/ml). Results showed that SNP in the MIC and the
      lower concentrations killed all of the used microorganisms. No difference was
      observed between the antimicrobial effect of ethanol-free mouthwash containing
      SNP and mouthwash containing SNP and ethanol (30,000 ug/ml). SNP has high
      antimicrobial effects at low concentrations and it can be a good alternative for
      ethanol (30,000 ug/ml) because ethanol is also irritating, especially to
      sensitive or inflamed mucosa. 

PMID- 23967392
TI  - Prospective pilot study on the incidence of infections caused by peripheral
      venous catheters at a general surgical ward.
AB  - Device-associated infections comprise a significant proportion of all nosocomial
      infections. In this prospective, observational pilot study the incidence of
      infections in 89 peripheral venous catheters (PVCs) was documented on a general
      surgical ward employing an infection data sheet developed by the Institute of
      Hygiene and Environmental Medicine, Greifswald in adherence to CDC standards for
      infections. 16 of 20 infections were documented during a four-week time period
      when medical students in the first four months of their practical year performed
      their compulsory rotation on the general surgical ward. Insufficient knowledge of
      adequate hygienic measures as well as non-compliance to aseptical procedural
      measures prior to and following insertion of a peripheral venous catheter are the
      assumed instigators of these infections. In order to ensure a uniform hygienic
      standard in the performance of applied procedures, it is essential that medical
      students during this practical year receive not only theoretical, but also hands
      on schooling prior to initiation of their subsequent official residency. 

PMID- 23967393
TI  - Microbial contamination of manually reprocessed, ready to use ECG lead wire in
      intensive care units.
AB  - BACKGROUND: A number of studies have shown that non-critical medical devices can
      be contaminated with pathogens, including those resistant to antibiotics and thus
      become a potential vector for transmission. Electrocardiography (ECG) lead wire
      are non-critical medical device which are always attached on patient skin during
      their stay in intensive care unit (ICU). In view of the patient's critical
      conditions and exposure to invasive procedures, identification and prevention of
      possible risks are important to prevent infection in ICUs. OBJECTIVE: The
      objective of this study was to determine the presence of bacterial and fungal
      contamination on cleaned and disinfected reusable ECG lead wires in intensive
      care units in a hospital. METHODS: A total of 408 cleaned ECG lead wires from 93
      bed-side ECG devices and 43 ECG lead wires from 5 portable ECG devices from 4
      intensive care units (ICUs) and 1 post-anaesthesia care unit (PACU) were sampled.
      ECG lead wires were stirred in 0.89% NaCl with added neutralizer for 30 seconds.
      Samples of the solutions were cultured directly on blood agar. The remaining
      solution was cultured on blood agar after sterile filtration. The number of
      colony forming units (CFUs) was counted and the microorganisms were identified.
      RESULTS: More than half of examined ECG lead wires (n=232; 51.4%) were
      contaminated with >30 CFUs/mL sample of bacteria or with risk pathogens. Gram
      positive bacteria were the most frequently isolated organisms; particularly,
      coagulase negative staphylococci (96%) and aerobic spore forming bacteria
      (71.2%). Compared to ICUs, PACU had significantly lower proportion of
      contaminated ECG lead wires (p<0.05). The proportion of contaminated ECG lead
      wires, as well as mean number of cfus per ECG lead wire, was also significantly
      lower among multi-wire ECG leads compared to single-wire ECG leads. CONCLUSIONS:
      Manually cleaned ECG lead wires may serve as a vector for transmission of
      nosocomial pathogens. The current reprocessing technique for ECG lead wires needs
      to be improved.

PMID- 23967394
TI  - Is routine replacement of i.v. administration sets required after each change of
      intermittently administrated antibiotic infusions?
AB  - AIM: Manufacturers' instructions recommend changing the infusion line together
      with the infusion bottle after each administration. We investigated if the
      complete infusion line may be microbiologically contaminated after short-time
      antibiotic and rinse-solution application. METHOD: Immediately after the change
      of an infusion administration set after 72 hours the remaining antibiotic
      solution was inactivated with yolk and cultured on blood agar for 48 hours at 36
      degrees C to detect possible contaminants. RESULTS: Among 87 investigated samples
      no microbial growth was detected. One sample which hadn't any contact to
      antibiotics yielded 1 colony forming unit (cfu) of coagulase-negative
      staphylococci. These results suggest that in case of consecutive antibiotic-short
      and rinse-infusions the infusion line may be in place up to 72 hours without
      contamination. This, however, may be only the case for infusion sets, which are
      in contact with antibiotics. If no antibiotic is administered, the infusion
      bottle and the infusion line must be renewed together for every change. To
      clarify this question into more detail, a larger consecutive study is required.
      CONCLUSION: I.v. administration sets without any contact to antibiotics must be
      changed together with their infusion bottle after administration. In case of
      consecutive antibiotic-short- and rinse-infusions our pilot study suggests using
      the i.v. administration sets for up to 72 hours without renewing it at every
      infusion-set exchange.

PMID- 23967395
TI  - Can breathing circuit filters help prevent the spread of influenza A (H1N1) virus
      from intubated patients?
AB  - INTRODUCTION: In March 2010, more than 213 countries worldwide reported
      laboratory confirmed cases of influenza H1N1 infections with at least 16,813
      deaths. In some countries, roughly 10 to 30% of the hospitalized patients were
      admitted to the ICU and up to 70% of those required mechanical ventilation. The
      question now arises whether breathing system filters can prevent virus particles
      from an infected patient from entering the breathing system and passing through
      the ventilator into the ambient air. We tested the filters routinely used in our
      institution for their removal efficacy and efficiency for the influenza virus A
      H1N1 (A/PR/8/34). METHODS: Laboratory investigation of three filters (PALL
      Ultipor((r)) 25, Ultipor((r)) 100 and Pall BB50T Breathing Circuit Filter,
      manufactured by Pall Life Sciences) using a monodispersed aerosol of human
      influenza A (H1N1) virus in an air stream model with virus particles quantified
      as cytopathic effects in cultured canine kidney cells (MDCK). RESULTS: The
      initial viral load of 7.74+/-0.27 log10 was reduced to a viral load of <=2.43
      log10, behind the filter. This represents a viral filtration efficiency of
      >=99.9995%. CONCLUSION: The three tested filters retained the virus input,
      indicating that their use in the breathing systems of intubated and mechanically
      ventilated patients can reduce the risk of spreading the virus to the breathing
      system and the ambient air.

PMID- 23967396
TI  - The role of surface disinfection in infection prevention.
AB  - BACKGROUND: The Rudolf Schuelke Foundation addresses topics related to hygiene,
      infection prevention and public health. In this context a panel of scientists
      from various European countries discussed "The Role of Surface Disinfection in
      Infection Prevention". The most important findings and conclusions of this
      meeting are summarised in the present consensus paper. AIM: Although the
      relevance of surface disinfection is increasingly being accepted, there are still
      a number of issues which remain controversial. In particular, the following
      topics were addressed: Transferral of microbes from surface to patients as a
      cause of infection, requirements for surface disinfectants, biocidal resistance
      and toxicity, future challenges. METHODS AND FINDINGS: After discussion and
      review of current scientific literature the authors agreed that contaminated
      surfaces contribute to the transmission of pathogens and may thus pose an
      infection hazard. Targeted surface disinfection based on a risk profile is seen
      as an indispensable constituent in a multibarrier approach of universal infection
      control precautions. Resistance and cross-resistance depend on the disinfectant
      agent as well as on the microbial species. Prudent implementation of surface
      disinfection regimens tested to be effective can prevent or minimize adverse
      effects. CONCLUSIONS: Disinfection must be viewed as a holistic process. There is
      a need for defining standard principles for cleaning and disinfection, for
      ensuring compliance with these principles by measures such as written standard
      operating procedures, adequate training and suitable audit systems. Also, test
      procedures must be set up in order to demonstrate the efficacy of disinfectants
      including new application methods such as pre-soaked wipes for surface
      disinfection.

PMID- 23967397
TI  - Questionnaire-based survey on structural quality of hospitals and nursing homes
      for the elderly, their staffing with infection control personal, and
      implementation of infection control measures in Germany.
AB  - From January to May 2012, 1,860 hospitals throughout Germany received a
      questionnaire encompassing 77 items. Additionally, 300 outpatient care services
      and 310 nursing homes for elderly in Berlin also received a 10-item questionnaire
      asking on their implemented infection control practices. All questionnaires were
      anonymous. A total of 229 completed questionnaires from hospitals, 14
      questionnaires from outpatient care services, and 16 questionnaires from nursing
      homes were eligible for further analysis. The lack of Infection Control
      physicians was identified as the largest issue. In hospitals sized 400-999 beds a
      gap of 71%, and in hospitals sized >=1,000 beds a gap of 17% was reported.
      Depending on the number of hospital beds, 13-29% of hospitals sized >=100 beds
      reported not havening one infection control nurse. Since based on the number of
      beds in larger institutions or in facilities caring for high-risk patients
      several infection control nurses may be required, the deficiency in infection
      control nurses may even be higher, particularly in secondary and tertiary care
      facilities. Furthermore, the analysis revealed that the legal requirements for
      surveillance and reporting of notifiable infectious diseases have not yet been
      implemented in 11% of the facilities. The implementation of antibiotic strategies
      did show significant gaps. However, deficiencies in the implemented measures for
      the prevention of surgical site infections were less frequent. Yet 12% of the
      participants did not have a dedicated infection control concept for their
      surgical services. Eight percent of hospitals were not prepared for an outbreak
      management and 10% did not have established regulations for wearing surgical
      scrubs. Deficiencies in waste disposal and the control of air-conditioning
      systems were also noted. Based on the results of this survey, conclusions on the
      optimal resource allocation for further improvement of patient safety may be
      drawn. While all participating nursing homes had some sort of infection control
      consultation, this only applied to 12 out of 16 outpatient nursing services.
      However, all 16 nursing services worked on the basis of an implemented infection
      control plan. Though legally binding hygiene recommendations have not yet been
      implemented for nursing homes, the necessity of infection control to assure
      patient safety has obviously been recognised throughout these services. 

PMID- 23967398
TI  - One-day point prevalence of emerging bacterial pathogens in a nationwide sample
      of 62 German hospitals in 2012 and comparison with the results of the one-day
      point prevalence of 2010.
AB  - BACKGROUND: Antibiotic resistance of bacterial pathogens is an emerging problem
      worldwide. To combat multidrug resistant organisms (MRDOs) networks of care
      providers have been established in all states in Germany. The HICARE-network, a
      project to combat MRDOs, founded by the Federal Ministry of Education and
      Research, has published data from 2010 of a voluntary, German-wide, multicenter
      point-prevalence survey in 2011 conducted in collaboration with the German
      Society of Hospital Hygiene. The aim of the present survey was the re-evaluation
      of the situation in 2012. METHOD: The survey was conducted as a voluntary,
      anonymous, point-prevalence in May 2012 using routine data of microbiological
      diagnostics of the hospitals. As in the former survey of 2010 it was
      differentiated between primary, secondary and tertiary care hospitals and only
      data from intensive care units, surgical and medical wards were collected. Based
      on the survey form used in 2010, an updated version was used including more
      pathogens and corrected issues observed in the former survey. Methicillin
      resistant Staphylococcus aureus (MRSA) (total as well as separated in hospital
      acquired (HA), community-acquired (CA) and lifestock-associated (LA) MRSA),
      vancomycin resistant Staphylococcus aureus (VRSA/GRSA), vancomycin resistant
      Enterococcus faecalis resp. Enterococcus faecium (VR-E. faecalis resp. VR-E.
      faecium), extended-spectrum-beta-lactamase-building (ESBL) E. coli (ESBL-EC) and
      Klebsiella pneumoniae (ESBL-KP), multiresistant Acinetobacter spp. (MAB),
      multiresistant Pseudomonas spp. (MRP), carbapenemase-producing Enterobacteriaceae
      (CRE) as well as Clostridium difficile (CD) infections and severe infections
      requiring ICU-treatment were included in the survey along with additional data on
      screening strategy, the equipment with infection control staff and possible
      confounders. RESULTS: Out of 1,550 hospitals asked to participate, 62 returned
      data (4%). Data from 56 hospitals including primary (26), secondary (20) and
      tertiary (10) care hospitals were analyzable (3.6%). The most frequently reported
      organisms were MRSA 1.53% [CI95: 1.32-1.75], followed by CDAD 1.30% [CI95: 1.11
      1.50], ESBL-EC 0.97% [CI95: 0.80-1.14], and ESBL-KP 0.27% [CI95: 0.18-0.36],
      regardless of the level of care. Prevalence of MRDOs depended on the level of
      care and on the type of ward, as expected. Overall prevalence was highest on
      intensive care wards, and prevalences were remarkably high on medical wards
      compared to surgical wards. All tertiary care providers employed their own
      infection control nurse, while only ~70% of the secondary and primary care
      hospitals did. Surprisingly, in two of the ten participating tertiary care
      providers neither an internal nor an external infection control doctor was
      available. DISCUSSION: With more than 13,000 patients in 56 hospitals distributed
      all over Germany, the survey included more than three times as many patients as
      the first survey and therefore not only adds valuable information about the
      epidemiology of emerging nosocomial pathogens, but also helps to raise awareness
      of the problem of antibacterial resistance in Germany. The prevalences reported
      seem to be comparable to the results of the former survey and of other surveys
      published. Some hospitals reported to have no infection control personnel
      available at all. This statement is in line with another survey published in this
      issue.

PMID- 23967399
TI  - GMS Hygiene and Infection Control.

PMID- 23967400
TI  - Ultrasonic enhancement of drug penetration in solid tumors.
AB  - Increasing the penetration of drugs within solid tumors can be accomplished
      through multiple ultrasound-mediated mechanisms. The application of ultrasound
      can directly change the structure or physiology of tissues or can induce changes
      in a drug or vehicle in order to enhance delivery and efficacy. With each
      ultrasonic pulse, a fraction of the energy in the propagating wave is absorbed by
      tissue and results in local heating. When ultrasound is applied to achieve mild
      hyperthermia, the thermal effects are associated with an increase in perfusion or
      the release of a drug from a temperature-sensitive vehicle. Higher ultrasound
      intensities locally ablate tissue and result in increased drug accumulation
      surrounding the ablated region of interest. Further, the mechanical displacement
      induced by the ultrasound pulse can result in the nucleation, growth and collapse
      of gas bubbles. As a result of such cavitation, the permeability of a vessel wall
      or cell membrane can be increased. Finally, the radiation pressure of the
      propagating pulse can translate particles or tissues. In this perspective, we
      will review recent progress in ultrasound-mediated tumor delivery and the
      opportunities for clinical translation. 

PMID- 23967401
TI  - Mechanistic targets and phytochemical strategies for breaking the obesity-cancer
      link.
AB  - The prevalence of obesity, an established risk and progression factor for many
      cancers, has increased dramatically in many countries over the past three
      decades. Worldwide, an estimated 600 million adults are currently obese. Thus, a
      better understanding of the mechanistic links between obesity and cancer is
      urgently needed to identify intervention targets and strategies to offset the
      procancer effects of obesity. This review synthesizes the evidence on key
      biological mechanisms underlying the obesity-cancer association, with particular
      emphasis on obesity-associated enhancements in growth factor signaling,
      inflammation, and perturbations in the tumor microenvironment. These interrelated
      pathways and processes that are aberrantly regulated in obese individuals
      represent mechanism-based targets for disrupting the obesity-cancer link using
      phytochemicals. 

PMID- 23967402
TI  - Quality of life following amputation or limb preservation in patients with lower
      extremity bone sarcoma.
AB  - PURPOSE: Although functional differences have been described between patients
      with lower extremity bone sarcoma with amputation and limb-preservation surgery,
      differences have not clearly been shown between the two groups related to quality
      of life. The purpose of the study was to determine if there is a difference in
      overall quality of life in lower extremity bone sarcoma survivors related to
      whether they had an amputation or a limb-preservation procedure while identifying
      psychological differences for further evaluation. The main hypothesis was that
      sparing a person's limb, as opposed to amputating it, would result in a better
      quality of life. PATIENTS AND METHODS: Eighty-two long-term survivors of lower
      extremity bone sarcoma were studied to make a comparison of the overall quality
      of life, pain assessment, and psychological evaluations in limb preservation and
      amputation patients. Forty-eight patients with limb preservation and thirty-four
      patients with amputations were enrolled in the study. Validated psychometric
      measures including the Quality of Life Questionnaire (QLQ), the Minnesota
      Multiphasic Personality Inventory, and visual analog scales were utilized.
      RESULTS: The overall quality of life of patients with limb preservation was
      significantly higher than patients with amputation (p-value < 0.01). Significant
      differences were noted in the categories of material well-being, job satisfiers,
      and occupational relations. CONCLUSION: The overall quality of life of patients
      with limb-preservation appears to be better than for those patients with
      amputation based on the QLQ in patients surviving lower extremity bone sarcoma.
      Further analysis needs to verify the results and focus on the categories that
      significantly affect the overall quality of life.

PMID- 23967404
TI  - What is the Role of the Bystander Response in Radionuclide Therapies?
AB  - Radionuclide therapy for cancer is undergoing a renaissance, with a wide range of
      radionuclide and clinical delivery systems currently under investigation.
      Dosimetry at the cellular and sub-cellular level is complex with inhomogeneity
      and incomplete targeting of all cells such that some tumor cells will receive
      little or no direct radiation energy. There is now sufficient preclinical
      evidence of a Bystander response which can modulate the biology of these un
      irradiated cells with current research demonstrating both protective and
      inhibitory responses. Dependence upon fraction of irradiated cells has also been
      found and the presence of functional gap junctions appears to be import for
      several Bystander responses. The selection of either high or low LET
      radionuclides may be critical. While low LET radionuclides appear to have a
      Bystander response proportional to dose, the dose-response from high LET
      radionuclides are more complex. In media transfer experiments a "U" shaped
      response curve has been demonstrated for high LET treatments. However this "U"
      shaped response has not been seen with co-culture experiments and its relevance
      remains uncertain. For high LET treatments there is a suggestion that dose rate
      effects may also be important with inhibitory effects noted with 125I labelling
      study and a stimulatory seen with 123I labelling in one study. 

PMID- 23967405
TI  - Borrelia burgdorferi aggrecanase activity: more evidence for persistent infection
      in Lyme disease.
AB  - Lyme disease is the most common tickborne illness in the world today. A recent
      study describes for the first time an enzyme produced by the spirochetal agent of
      Lyme disease, Borrelia burgdorferi, that cleaves aggrecan, a proteoglycan found
      in joints and connective tissue. Discovery of the spirochetal aggrecanase raises
      many questions about the pathogenesis of Lyme arthritis and lends support to the
      concept of persistent B. burgdorferi infection in patients with chronic Lyme
      disease symptoms. 

PMID- 23967403
TI  - Vascular permeability and drug delivery in cancers.
AB  - The endothelial barrier strictly maintains vascular and tissue homeostasis, and
      therefore modulates many physiological processes such as angiogenesis, immune
      responses, and dynamic exchanges throughout organs. Consequently, alteration of
      this finely tuned function may have devastating consequences for the organism.
      This is particularly obvious in cancers, where a disorganized and leaky blood
      vessel network irrigates solid tumors. In this context, vascular permeability
      drives tumor-induced angiogenesis, blood flow disturbances, inflammatory cell
      infiltration, and tumor cell extravasation. This can directly restrain the
      efficacy of conventional therapies by limiting intravenous drug delivery. Indeed,
      for more effective anti-angiogenic therapies, it is now accepted that not only
      should excessive angiogenesis be alleviated, but also that the tumor vasculature
      needs to be normalized. Recovery of normal state vasculature requires diminishing
      hyperpermeability, increasing pericyte coverage, and restoring the basement
      membrane, to subsequently reduce hypoxia, and interstitial fluid pressure. In
      this review, we will introduce how vascular permeability accompanies tumor
      progression and, as a collateral damage, impacts on efficient drug delivery. The
      molecular mechanisms involved in tumor-driven vascular permeability will next be
      detailed, with a particular focus on the main factors produced by tumor cells,
      especially the emblematic vascular endothelial growth factor. Finally, new
      perspectives in cancer therapy will be presented, centered on the use of anti
      permeability factors and normalization agents. 

PMID- 23967406
TI  - The human urinary microbiome; bacterial DNA in voided urine of asymptomatic
      adults.
AB  - The urinary microbiome of healthy individuals and the way it alters with ageing
      have not been characterized and may influence disease processes. Conventional
      microbiological methods have limited scope to capture the full spectrum of
      urinary bacterial species. We studied the urinary microbiota from a population of
      healthy individuals, ranging from 26 to 90 years of age, by amplification of the
      16S rRNA gene, with resulting amplicons analyzed by 454 pyrosequencing. Mid
      stream urine (MSU) was collected by the "clean-catch" method. Quantitative PCR of
      16S rRNA genes in urine samples, allowed relative enumeration of the bacterial
      loads. Analysis of the samples indicates that females had a more heterogeneous
      mix of bacterial genera compared to the male samples and generally had
      representative members of the phyla Actinobacteria and Bacteroidetes. Analysis of
      the data leads us to conclude that a "core" urinary microbiome could potentially
      exist, when samples are grouped by age with fluctuation in abundance between age
      groups. The study also revealed age-specific genera Jonquetella, Parvimonas,
      Proteiniphilum, and Saccharofermentans. In conclusion, conventional
      microbiological methods are inadequate to fully identify around two-thirds of the
      bacteria identified in this study. Whilst this proof-of-principle study has
      limitations due to the sample size, the discoveries evident in this sample data
      are strongly suggestive that a larger study on the urinary microbiome should be
      encouraged and that the identification of specific genera at particular ages may
      be relevant to pathogenesis of clinical conditions. 

PMID- 23967408
TI  - The roundtrip to Fairbanks: the circumpolar health movement comes full circle,
      part II.
AB  - OBJECTIVES: Evaluate the course of the International Union for Circumpolar Health
      (IUCH) and the Proceedings of the International Congress(s) on Circumpolar Health
      (ICCH) in the context of the concomitant historical events. Make recommendations
      for future circumpolar health research. STUDY DESIGN: Medline search and
      historical archive search of ICCH Proceedings. METHODS: Search of all PubMed
      resources from 1966 concerning the circumpolar health movement. Two University of
      Alaska, Anchorage Archive Collections were searched: the C. E. Albrecht and Frank
      Pauls Archive Collections. RESULTS: Fourteen sets of Proceedings manuscripts and
      one set of Proceedings Abstracts were evaluated. There was a trend towards
      consistent use of the existing journals with indexing in Index Medicus; shorter
      intervals between the Congress and Proceedings manuscript publication; and
      increased online availability of either the Table of Contents or Proceedings
      citations. Recent additions include online publication of full-length manuscripts
      and 2 instances of full peer-review evaluations of the Proceedings manuscripts.
      These trends in Proceedings publication are described within the course of
      significant events in the circumpolar health movement. During this period, the
      IUCH funds are at an all-time low and show little promise of increasing, unless
      significant alternative funds strategies are pursued. CONCLUSIONS: The IUCH has
      matured politically over these years, but some of the same questions persist over
      the years. There has been a trend towards more rapid dissemination of scientific
      content, more analytic documentation of epidemiologic study design and trend
      towards wider dissemination of scientific content through the Internet.
      Significant progress in each of those areas is still possible and desirable. In
      the meantime, the IUCH should encourage alternative funding strategies by
      developing a foundation to support on-going expenses, for example Hildes awards;
      explore venues to finance Council President and At-Large members travel costs;
      and seek grants to fund special projects, for example special supplements in the
      IJCH.

PMID- 23967409
TI  - "I only smoke when I have nothing to do": a qualitative study on how smoking is
      part of everyday life in a Greenlandic village.
AB  - BACKGROUND: Smoking-related illnesses, such as chronic obstructive pulmonary
      disease, cardiovascular disease and lung cancer, are common in Greenland. Factors
      such as age, gender, cigarette use, restricted smoking at home and socio-economic
      determinants are well-known predictors for smoking and smoking cessation. In
      2005, 66% of the adult population in were Greenland smokers, despite widespread
      smoking cessation campaigns. It is therefore imperative to identify the factors
      that influence the low levels of smoking cessation to be able to offer cessation
      interventions of high quality. AIM: To develop knowledge about how smoking forms
      an incorporated part of a social and cultural context in the daily lives of
      unskilled residents of a small town in northern Greenland. DESIGN: An
      ethnographic field study was carried out in 2010, including participant
      observation, informal conversation with health professionals and semi-structured
      interviews with 4 smokers (2 women and 2 men). Data were analysed with a
      phenomenological hermeneutic approach. RESULTS: All informants were daily
      smokers. During work hours, they smoked fewer cigarettes due to control policy as
      well as having something to do. At home, they smoke more during leisure time.
      Having time on one's hands can be a factor in smokers remaining as smokers. It
      appears that smokers seem to consider themselves to be stigmatised. This may be
      one reason for wanting to stop smoking. Smokers ask how to quit and also ask for
      help to give up smoking with regard to medical treatment for withdrawal symptoms.
      Serious illness and pregnancy both appear to be triggers to consider giving up
      smoking. Severe withdrawal symptoms and lack of knowledge about how to give up
      smoking are barriers to participants achieving their goal. CONCLUSION: Prevention
      initiatives should be targeted at all smokers and a smoking cessation service
      should be developed, where smokers are supervised and receive medical treatment
      for withdrawal symptoms.

PMID- 23967407
TI  - Microorganism and filamentous fungi drive evolution of plant synapses.
AB  - In the course of plant evolution, there is an obvious trend toward an increased
      complexity of plant bodies, as well as an increased sophistication of plant
      behavior and communication. Phenotypic plasticity of plants is based on the polar
      auxin transport machinery that is directly linked with plant sensory systems
      impinging on plant behavior and adaptive responses. Similar to the emergence and
      evolution of eukaryotic cells, evolution of land plants was also shaped and
      driven by infective and symbiotic microorganisms. These microorganisms are the
      driving force behind the evolution of plant synapses and other neuronal aspects
      of higher plants; this is especially pronounced in the root apices. Plant
      synapses allow synaptic cell-cell communication and coordination in plants, as
      well as sensory-motor integration in root apices searching for water and mineral
      nutrition. These neuronal aspects of higher plants are closely linked with their
      unique ability to adapt to environmental changes. 

PMID- 23967410
TI  - Tobacco use prevalence--disentangling associations between Alaska Native race,
      low socio-economic status and rural disparities.
AB  - BACKGROUND: Tobacco use rates are exceptionally high among indigenous people in
      North America. Alaska Native, low socio-economic status (SES) and rural
      communities are high-priority populations for Alaska's Tobacco Control program.
      DESIGN: For the purpose of better informing tobacco control interventions, we
      conducted a descriptive study to describe high-priority groups using prevalence
      based and proportion-based approaches. METHODS: With data from 22,311 adults
      interviewed for Alaska's 2006-2010 Behavioral Risk Factor Surveillance System
      (BRFSS), we used stratified analysis and logistic regression models to describe
      the current use of cigarettes and smokeless tobacco (SLT) (including iq'mik, a
      unique Alaska Native SLT product) among the 3 populations of interest. RESULTS:
      "Population segments" were created with combinations of responses for Alaska
      Native race, SES and community type. We identified the highest prevalence and
      highest proportion of tobacco users for each type of tobacco by "segment". For
      cigarette smoking, while the largest proportion (nearly one-third) of the state's
      smokers are non-Native, high SES and live in urban settings, this group also has
      lower smoking prevalence than most other groups. Alaska Native, low SES, rural
      residents had both high smoking prevalence (48%) and represented a large
      proportion of the state's smokers (nearly 10%). Patterns were similar for SLT,
      with non-Native high-SES urban residents making up the largest proportion of
      users despite lower prevalence, and Alaska Native, low SES, rural residents
      having high prevalence and making up a large proportion of users. For iq'mik use,
      Alaska Native people in rural settings were both the highest prevalence and
      proportion of users. CONCLUSION: While Alaska Native race, low SES status and
      community of residence can be considered alone when developing tobacco control
      interventions, creating "population segments" based on combinations of factors
      may be helpful for tailoring effective tobacco control strategies and messaging.
      Other countries or states may use a similar approach for describing and
      prioritizing populations.

PMID- 23967411
TI  - The cost of lower respiratory tract infections hospital admissions in the
      Canadian Arctic.
AB  - BACKGROUND: Inuit infants who reside in the Nunavut (NU) regions of Arctic Canada
      have extremely high rates of lower respiratory tract infections (LRTIs)
      associated with significant health expenditures, but the costs in other regions
      of Arctic Canada have not been documented. OBJECTIVE: This prospective
      surveillance compares, across most of Arctic Canada, the rates and costs
      associated with LRTI admissions in infants less than 1 year of age, and the days
      of hospitalization and costs adjusted per live birth. DESIGN: This was a hospital
      based surveillance of LRTI admissions of infants less than 1 year of age,
      residing in Northwest Territories (NT), the 3 regions of Nunavut (NU); [Kitikmeot
      (KT), Kivalliq (KQ) and Qikiqtani (QI)] and Nunavik (NK) from 1 January 2009 to
      30 June 2010. Costs were obtained from the territorial or regional governments
      and hospitals, and included transportation, hospital stay, physician fees and
      accommodation costs. The rates of LRTI hospitalizations, days of hospitalization
      and associated costs were calculated per live birth in each of the 5 regions.
      RESULTS: There were 513 LRTI admissions during the study period. For NT, KT, KQ,
      QI and NK, the rates of LRTI hospitalization per 1000 live births were 38, 389,
      230, 202 and 445, respectively. The total days of LRTI admission per live birth
      were 0.25, 3.3, 2.6, 1.7 and 3 for the above regions. The average cost per live
      birth for LRTI admission for these regions was $1,412, $22,375, $14,608, $8,254
      and $10,333. The total cost for LRTI was $1,498,232 in NT, $15,662,968 in NU and
      $3,874,881 in NK. Medical transportation contributed to a significant proportion
      of the costs. CONCLUSION: LRTI admission rates in NU and Nunavik are much higher
      than that in NT and remain among the highest rates globally. The costs of these
      admissions are exceptionally high due to the combination of very high rates of
      admission, very expensive medical evacuations and prolonged hospitalizations.
      Decreasing the rates of LRTI in this population could result in substantial
      health savings.

PMID- 23967412
TI  - Characteristics of the Frontier Extended Stay Clinic: a new facility model.
AB  - PURPOSE: In 2004, 5 remote clinics--4 in rural frontier communities in Alaska and
      1 in Washington--were funded to pilot and examine the effectiveness and
      appropriateness of a new facility model. Transporting patients from these
      locations to higher levels of care is not always possible requiring these
      facilities to expand their scope of services and provide care for extended
      periods. The Frontier Extended Stay Clinic (FESC) model is staffed and equipped
      to provide the combined services usually found in the separate settings of an
      outpatient primary-care clinic, inpatient acute care hospital and emergency room.
      This is a descriptive study of the characteristics of these pilot facilities and
      an analysis of patient utilization and outcomes. METHODS: The 5 clinics collected
      outcome data for 2,226 extended-stay encounters of 4 hours or longer from 15
      September 2005 to 14 September 2010. Data from these extended-stay encounters
      were summarized, and descriptive statistics were used to describe: number and
      duration of encounters, when the encounters started, chief compliant, discharge
      diagnoses, transfer destination, Medicare and Medicaid eligibility, and type of
      encounter. FINDINGS: From 2005 to 2010, the mean duration of an extended-stay
      encounter was 9.1 hours. All of the clinics experienced many extended-stay
      encounters that were initiated or continued after normal business hours. The 5
      most frequent diagnoses at discharge for extended encounters were cardiovascular,
      gastrointestinal, injury, substance abuse and pneumonia/bronchitis. Almost half,
      47.6%, of extended-stay encounters resulted in discharge of the patient without a
      need for either non-urgent follow-up referral or transport. Extended-stay
      encounters that ended in a patient being transported to another medical facility
      were 43.7% of the total. More than a quarter (26.9%) of extended-stay encounters
      were eligible for Medicare payment. CONCLUSION: While many of communities can
      support a facility for primary care, there is an on-going need for facilities in
      remote frontier areas to also provide emergent and extended-stay care. The FESC
      can provide access to primary, emergent and extended-stay services in these
      locations.

PMID- 23967413
TI  - Comparative analysis of clinical, electrocardiographic, angiographic and
      echocardiographic data of indigenous and non-indigenous residents of Yakutia with
      coronary artery atherosclerosis.
AB  - AIM: The aim of the study is to compare clinical, angiographic,
      electrocardiographic, echocardiographic data between indigenous and non
      indigenous residents of Yakutia. STUDY DESIGN: We performed cross-sectional
      analysis of the Registry of Selective Coronary Angiography (SCAG) of the Yakutsk
      Republican Hospital for the period from 2004 to 2007. All patients (n = 1,233)
      were admitted to hospital from all 35 regions of the Sakha Republic (Yakutia).
      Initially, 12 (1%) patients, who had abnormal coronary arteries and 259 (21%)
      patients with normal coronary arteries were excluded from this study. From the
      remaining 962 (78%) patients with detected coronary artery atherosclerosis 394
      (41%) patients were excluded for having congenital heart malformations due to
      possible influence on the outcomes of examination for myocardial hypertrophy.
      Finally, only 568 patients were selected for further examinations. METHODS: We
      analyzed clinical data, and the findings of selective angiography, multi-detector
      computed tomography (CT), electrocardiography (ECG), 24-hour Holter ECG
      monitoring and echocardiography. RESULTS: (a) In the Sakha Republic (Yakutia)
      single-vessel coronary disease, coronary stenosis with 50-75% and 75-90% of
      constriction were detected more often among indigenous males, while multiple
      vessel coronary stenosis was detected more often among non-indigenous males as
      well as stenosis with more than 90% of constriction. Lower calcium score mean
      (349.1 +/- 129.8 vs. 621.8 +/- 115.2) was observed among indigenous patients
      compared to non-indigenous patients; (b) Painless myocardial infarction, painless
      ischaemia, arterial hypertension and atrial fibrillation were detected more often
      among indigenous male compared to non-indigenous participants; (c) Based on the
      results of ECG and echocardiographic examinations, left ventricular (LV)
      hypertrophy, particular eccentric type of hypertrophy, was found more commonly
      among indigenous than non-indigenous males; and (d) By laboratory findings,
      indigenous males had significantly lower triglyceride levels, while platelet
      counts were higher compared to non-indigenous patients. Obesity was observed less
      frequently among indigenous men compared to non-indigenous men. CONCLUSION: The
      differences observed in this study are disputable and call for further studies.
      Collection of reliable data for women should be the aim of future studies.

PMID- 23967414
TI  - Rebuilding northern foodsheds, sustainable food systems, community well-being,
      and food security.
AB  - BACKGROUND: Multiple climatic, environmental and socio-economic pressures have
      accumulated to the point where they interfere with the ability of remote rural
      Alaska Native communities to achieve food security with locally harvestable food
      resources. The harvest of wild foods has been the historical norm, but most
      Alaska Native villages are transitioning to a cash economy, with increasing
      reliance on industrially produced, store-bought foods, and with less reliable
      access to and reliance on wild, country foods. While commercially available
      market foods provide one measure of food security, the availability and quality
      of market foods are subject to the vagaries and vulnerabilities of the global
      food system; access is dependent on one's ability to pay, is limited to what is
      available on the shelves of small rural stores, and, store-bought foods do not
      fulfill the important roles that traditional country foods play in rural
      communities and cultures. Country food access is also constrained by rising
      prices of fuel and equipment, a federal and state regulatory framework that
      sometimes hinders rather than helps rural subsistence users who need to access
      traditional food resources, a regulatory framework that is often not responsive
      to changes in climate, weather and seasonality, and a shifting knowledge base in
      younger generations about how to effectively harvest, process and store wild
      foods. OBJECTIVE: The general objective is to provide a framework for
      understanding the social, cultural, ecological and political dimensions of rural
      Alaska Native food security, and to provide information on the current trends in
      rural Alaska Native food systems. DESIGN: This research is based on our long-term
      ethnographic, subsistence and food systems work in coastal and interior Alaska.
      This includes research about the land mammal harvest, the Yukon River and coastal
      fisheries, community and village gardens, small livestock production and red meat
      systems that are scaled appropriately to village size and capacity, and food
      system intervention strategies designed to rebuild local and rural foodsheds and
      to restore individual and community health. RESULTS: The contemporary cultural,
      economic and nutrition transition has severe consequences for the health of
      people and for the viability of rural communities, and in ways that are not well
      tracked by the conventional food security methodologies and frameworks. This
      article expands the discussion of food security and is premised on a holistic
      model that integrates the social, cultural, ecological, psychological and
      biomedical aspects of individual and community health. CONCLUSION: We propose a
      new direction for food-system design that prioritizes the management of place
      based food portfolios above the more conventional management of individual
      resources, one with a commitment to as much local and regional food production
      and/or harvest for local and regional consumption as is possible, and to
      community self-reliance and health for rural Alaska Natives.

PMID- 23967415
TI  - Susceptibility to hypoxia and breathing control changes after short-term cold
      exposures.
AB  - BACKGROUND: Hypoxia is the reduction of oxygen availability due to external or
      internal causes. There is large individual variability of response to hypoxia.
      OBJECTIVE: The aim of this study was to define individual and typological
      features in susceptibility to hypoxia, its interrelation with hypoxic and
      hypercapnic ventilatory responses (HVR and HCVR, respectively) and their changes
      after cold acclimation. DESIGN: Twenty-four healthy men were tested. HVR and HCVR
      were measured by the rebreathing method during hypoxic and hypercapnic tests,
      respectively. These tests were carried out in thermoneutral conditions before and
      after cold exposures (nude, at 13 degrees C, 2 h daily, for 10 days).
      Susceptibility to hypoxia (sSaO2) was determined as haemoglobin saturation slope
      during hypoxic test. RESULTS: It was found that HVR and HCVR significantly
      increased and susceptibility to hypoxia (sSaO2) tended to decrease after cold
      acclimation. According to sSaO2 results before cold exposures, the group was
      divided into 3: Group 1--with high susceptibility to hypoxia, Group 2--medium and
      Group 3--low susceptibility. Analysis of variances (MANOVA) shows the key role of
      susceptibility to hypoxia and cold exposures and their interrelation. Posterior
      analysis (Fisher LSD) showed significant difference in susceptibility to hypoxia
      between the groups prior to cold acclimation, while HVR and HCVR did not differ
      between the groups. After cold acclimation, susceptibility to hypoxia was not
      significantly different between the groups, while HCVR significantly increased in
      Groups 1 and 3, HVR significantly increased in Group 3 and HCVR, HVR did not
      change in Group 2. CONCLUSIONS: Short-term cold exposures caused an increase in
      functional reserves and improved oxygen supply of tissues in Group 1. Cold
      exposure hypoxia has caused energy loss in Group 3. Group 2 showed the most
      appropriate energy conservation reaction mode to cold exposures. No relation was
      found between the thermoregulation and the susceptibility to hypoxia.

PMID- 23967416
TI  - High prevalence of medicine-induced attempted suicides among females in Nuuk,
      Greenland, 2008-2009.
AB  - BACKGROUND: The suicide rate in Greenland, especially among men, is among the
      highest in the world. Attempted suicide rates may be high also. However, the
      rates of attempted suicide are unknown. OBJECTIVE: We aimed to estimate the age-
      and gender-specific incidence of attempted suicide using medicine in Nuuk in 2008
      2009. DESIGN: An observational retrospective study of consecutive medical records
      on patients admitted to Dronning Ingrids Hospital in Nuuk in 2008-2009 with
      possible medicine intoxication. RESULTS: Seventy-four (60 females and 14 men)
      cases of attempted suicide using medicine were included. Of those, 43 used
      paracetamol alone or in combination with other medicine. The incidence of
      attempted suicide using medicine was higher among females than males (p < 0.001).
      The highest incidence of attempted suicide with paracetamol was found among women
      aged 20-24 years (0.84%). The highest incidence of suicide with medication (1.31
      per 100 inhabitants per year) was among women aged 15-19 years. CONCLUSIONS: The
      incidence of attempted suicide using medicine was high in Nuuk, Greenland,
      especially among women. The highest incidence of suicide attempts with medication
      was observed among women in the age group 15-19 years (1.31%). This may reflect
      psychosocial vulnerability among young people in Greenland. Initiatives to
      improve living conditions for children and adolescents are highly recommended to
      be initiated immediately.

PMID- 23967417
TI  - Helicobacter pylori incidence and re-infection in the Aklavik H. pylori Project.
AB  - BACKGROUND: The Aklavik H. pylori Project (AHPP) (www.canhelpworkinggroup.ca) is
      a community-driven project examining Helicobacter pylori infection and its
      influence on health in a diverse Aboriginal community in the Northwest
      Territories. Initial research revealed that 58% of 333 participants who underwent
      a urea breath test (UBT) between 2007 and 2010 were H. pylori-positive. From 2008
      to 2010, we offered treatment to H. pylori-positive participants and 113
      consented to this treatment. OBJECTIVE: We estimated H. pylori incidence in AHPP
      participants who initially tested negative and the re-infection frequency in
      initially positive participants who were successfully treated to clear the
      infection. METHODS: Participants who were initially H. pylori-negative or
      negative after treatment during 2008-2010 were eligible for inclusion. From
      November 2011 to June 2012, participants were offered a UBT and the samples were
      analyzed using infrared spectroscopy (IRIS). Participants with a positive test
      result were classified as new cases for estimating incidence among participants
      testing negative at baseline and re-infection among those successfully treated
      for H. pylori infection. RESULTS: Among 38 initially negative participants,
      follow-up UBT showed that 33 remained negative, 3 were positive, and 2 had
      uncertain status. The estimated incidence proportion during the follow-up period
      was 8.3% (95% CI: 1.8-22.0%). Among 43 participants with a negative post
      treatment UBT, 41 remained negative and 2 were positive. The estimated re
      infection proportion during the follow-up period was 4.7% (95% CI: 0.6-16.0%).
      The frequency of new cases was similar in males and females. Aboriginal
      participants had a combined re-infection/incidence rate of 2.4% per year (95% CI:
      0.8-5.9% per year). All 9 non-Aboriginal participants remained free from
      infection throughout the study period, as did all 23 participants aged 55 years
      and above. CONCLUSIONS: The AHPP has substantially reduced the burden of
      infection in Aklavik since 2008. Continued monitoring, treatment, community
      engagement and knowledge translation activities are needed to ensure a lasting
      benefit of the project.

PMID- 23967418
TI  - Health aspects of Arctic exploration--Alaska's medical history based on the
      research files of Dr. Robert Fortuine.
AB  - BACKGROUND: Robert Fortuine provided basic medical care to Alaska Native people,
      chronicled the Health Aspects of Arctic Exploration and through a number of
      influential publications, was the first to thoroughly document and analyse
      Alaska's Medical History. This overview of his published work will provide the
      reader with a detailed overview, so that they can begin to explore Dr. Fortuine's
      many published works in more detail. OBJECTIVE: This review will explore Alaska's
      Medical History and the Health Aspects of Arctic Exploration through the research
      files and the 10 most significant publications of Dr. Robert Fortuine. DESIGN:
      Review of Dr. Fortuine's major works and the master bibliography has over 3,000
      references and 81 subjects. The master bibliography is a merger of 55 separate
      bibliographies, which provides a wealth of bibliographic information. This paper
      will describe his 10 most significant publications, 2 of which began as a journal
      issue. RESULTS: Dr. Fortuine was a prolific writer throughout his career,
      publishing 134 articles and books. He wrote papers and books on Alaska's medical
      history, tuberculosis and health care delivery from Russian-America through the
      Public Health Service efforts in the territory and then the State of Alaska. The
      master bibliography has over 3,000 references and 81 subjects. This list has a
      significant number of entries for tuberculosis with almost one-third of the
      entries including this heading. Others dwell on the history of "pre-contact"
      health, the history of Alaska Native health care, the history of the Alaska
      Department of Health, especially the tuberculosis programme, the role of the US
      Public Health Service and traditional medicine. He completely reviewed every
      Governors' and the US Surgeon General's reports in regard to Alaska content. This
      paper describes his 10 most significant publications. CONCLUSIONS: Robert
      Fortuine's published works offer a wealth of information and insight into
      Alaska's Medical History and the Health Aspects of Arctic Exploration. As is
      probably true for many historians, he began small, creating a bibliography and
      adapting a talk before tackling his first full-length book. Readers who sample
      his many works will be enriched and enlightened.

PMID- 23967419
TI  - Navigating the cultural geography of indigenous peoples' attitude toward genetic
      research: the Ohana (family) heart project.
AB  - BACKGROUND: Little is known about the burden of heart failure among indigenous
      populations, including Native Hawaiians (NH). Recent concerns about genetic
      research in the NH community resonate with similar concerns raised by American
      Indian, Alaskan Native and Canadian First Nations communities and have raised
      questions about the best way to proceed with studies involving biological
      specimens. OBJECTIVE: To help us plan a study to investigate disparities in heart
      failure incidence and outcomes in a NH community, we performed a qualitative
      study to examine the community's expectations for heart failure research that
      includes the collection of biological specimens. METHODS: Eighty-five NH with a
      personal or family history of heart failure, who lived in a geographically
      isolated community in the state of Hawai'i participated in 1 of 16 semi
      structured interviews. Interviews were conducted in a standard manner, with open
      ended questions designed to explore their expectations for a heart failure
      research study that included the collection of biological specimens. Interviews
      were analyzed thematically through iterative readings and coding. RESULTS: four
      key themes regarding heart failure research with the use of biological specimens
      characterized their expectations: (a) Need to foster trust between investigator
      and community; (b) Establish a partnership with the community to identify needs
      and goals; (c) Need for mutual benefit to investigator and community; (d)
      Identification of a key voice to represent the community. Participants expressed
      strong support for research. However, the strength of that support was directly
      related to the strength of the relationship between the research team and the
      community. The collection of biological specimens for genetic analyses was not an
      explicit concern or barrier per se. CONCLUSIONS: It appears feasible to conduct a
      heart failure research study that includes the collection of biological samples.
      However, success will likely require addressing the community's expectations,
      including the need for a long-term partnership built on trust and mutual benefit,
      and a key voice to represent the community.

PMID- 23967420
TI  - Culturally tailored postsecondary nutrition and health education curricula for
      indigenous populations.
AB  - BACKGROUND: In preparation for the initial offering of the University of Alaska
      Fairbanks (UAF), Interior-Aleutians Campus Rural Nutrition Services (RNS)
      program, a literature review was conducted to establish the need for the proposed
      program and to substantiate the methodology for delivering integrated, culturally
      tailored postsecondary education and extension to Alaska Natives and rural
      Alaskans. There was a striking absence of peer-reviewed journal articles
      describing culturally tailored postsecondary health curricula for indigenous
      populations. OBJECTIVE: To complete and discuss a current (November 2012)
      literature review for culturally tailored postsecondary health curricula designed
      and delivered for indigenous populations. METHODS/DESIGN: The author conducted an
      expanded online search that employed multiple configurations of key terms using
      Google and Google Scholar, as well as pertinent sources. The author located
      archived reports in person and contacted authors by email. RESULTS: The expanded
      search produced a modest amount of additional literature for review. A
      disappointing number of publications describing or evaluating culturally tailored
      postsecondary health curricula in mainstream institutions are available. Related
      resources on culturally tailored extension and resources for the development and
      delivery of culturally tailored nutrition and health curricula were identified.
      CONCLUSIONS: The present results demonstrate a significant absence of literature
      on the topic, which may or may not indicate the absence of sufficient culturally
      tailored postsecondary health curricula for indigenous populations. There are
      indications that culturally tailored postsecondary health curricula for
      indigenous populations have the potential to effectively address certain issues
      of health literacy and health disparities.

PMID- 23967421
TI  - Chronic obstructive pulmonary diseases related health resources allocation in
      hunan province of china.
AB  - BACKGROUND: Information about Chronic obstructive pulmonary diseases (COPD)
      related health resources allocation in China is very limited. The aim of the
      study was to explore the distribution of COPD-related health resources allocation
      among different levels public hospitals (PHs) in Hunan Province of central south
      China. METHODS: We randomly collected data from 57 Public Hospitals (PHs) at 3
      different levels in Hunan province as well as 893 pulmonary physicians (PPs) who
      worked there in 2009. Questionnaires based on the recommendations of COPD
      guideline were designed, including availability of spirometers, inhaled agents
      for COPD and COPD-related health education for local residents, as well as PPs'
      educational levels. RESULTS: Spirometers equipped ratio in 3(rd) level PHs was
      much higher than 1(st), 2(nd) PHs. The disparity varied vastly form 0% to 100%.
      The inhaled agents equipped ratio was 5.56%, 70.85% and 100% respectively for the
      1(st), 2(nd) and 3(rd) levels PHs. No 1(st) level PHs launched COPD-related
      healthcare education for local residents, only 10 of 24 for the 2(nd) level PHs
      and 10 of 15 for the 3(rd) level PHs. PPs of high educational levels concentrate
      in 3(rd) levels PHs, however, PPs working in 1(st) levels PHs and 2(nd) levels
      PHs were mainly low and median educational levels PPs' knowledge of COPD of 3(rd)
      levels PHs was much better than of 1(st) levels PHs and 2(nd) levels PHs.
      CONCLUSION: The extreme imbalance and disparity existed in COPD-related health
      resources allocation at three levels PHs in central south China. Inequity and
      insufficient in COPD-related health resources in 1(st) and 2(nd) levels PHs
      should be improved.

PMID- 23967422
TI  - Cost effectiveness of adopted quality requirements in hospital laboratories.
AB  - BACKGROUND: The present study was designed in quasi-experiment to assess adoption
      of the essential clauses of particular clinical laboratory quality management
      requirements based on international organization for standardization (ISO 15189)
      in hospital laboratories and to evaluate the cost effectiveness of compliance to
      ISO 15189. METHODS: The quality management intervention based on ISO 15189 was
      conceded through three phases; pre - intervention phase, Intervention phase and
      Post-intervention phase. RESULTS: In pre-intervention phase the compliance to ISO
      15189 was 49% for study group vs. 47% for control group with P value 0.48, while
      the post intervention results displayed 54% vs. 79% for study group and control
      group respectively in compliance to ISO 15189 and statistically significant
      difference (P value 0.00) with effect size (Cohen's d) of (0.00) in pre
      intervention phase and (0.99) in post - intervention phase. The annual average
      cost per-test for the study group and control group was 1.80 +/- 0.25 vs. 1.97 +/
      0.39, respectively with P value 0.39 whereas the post-intervention results
      showed that the annual average total costs per-test for study group and control
      group was 1.57 +/- 0.23 vs 2.08 +/- 0.38, P value 0.019 respectively, with cost
      effectiveness ratio of (0.88) in pre -intervention phase and (0.52) in post
      intervention phase. CONCLUSION: The planned adoption of quality management
      requirements (QMS) in clinical laboratories had great effect to increase the
      compliance percent with quality management system requirement, raise the average
      total cost effectiveness, and improve the analytical process capability of the
      testing procedure.

PMID- 23967423
TI  - Depression, prevalence and some risk factors in elderly nursing homes in tehran,
      iran.
AB  - BACKGROUND: The most common geriatric psychiatric disorder is depression, known
      to be a multi factorial disorder. However, the influence of common preventable
      factors is yet to be discovered. This study was designed to evaluate the
      prevalence of depression and some possible risk factors in elderly residents of
      nursing homes in Iran. METHODS: Data on demographic characteristics, nutritional
      and health status of 244 residents aged 60 years or older were collected from
      seventeen nursing homes in Tehran, Iran, during 2010 to 2012. Depression was
      assessed and classified according to the 15-item GDS. Univariate and then
      multivariate complex sample survey ordinal regression analysis was performed to
      investigate the association between depression and the risk factors. RESULTS: The
      average age of the 244 cases studied was 75.8 (+/-8.7) years, 53.3% were female
      (of whom 74.2% were housewives), 43.4% illiterate, and 32.0% were divorced or
      were living separately. The percentages of non-depressed, mild, moderate and
      severe depression were 9.8%, 50.0%, 29.5% and 10.7%, respectively. Multivariate
      analysis showed that dissatisfaction with personnel of nursing homes and food
      quality had odds ratios of 2.91 (1.33-6.36) and 2.64 (1.44-4.87), corresponding
      to greater odds of having a higher grade depression. Moreover, those who rested
      or walked had significantly higher risk of a more severe depression in comparison
      with those who did not (OR of 2.25 (1.50-3.38) and 1.98 (1.24-3.18),
      respectively), however, studying had a protective odds ratio of 0.17 (0.13-0.22).
      CONCLUSION: Depression was very common in our sample and their lifestyle
      influenced its prevalence.

PMID- 23967424
TI  - The Interrelations among the Perception of Parental Styles and Psychological Well
      Being in Adolescence: A Longitudinal Study.
AB  - BACKGROUND: This longitudinal study aims to examine the relationships between the
      perception of parental style, hope, self-esteem and Eysenck's psychoticism
      dimension throughout the span of four years. METHODS: The sample was composed of
      884 students from the Wollongong Youth Study, which commenced when students
      entered high school. During the course of the 4 years of the study, each
      participant completed the test booklets each time data was collected. Data was
      analyzed using one way ANOVA, Post-hoc test, Repeated Measurement, Pearson and
      Partial Correlation and General Linear Model in order to provide the aims of the
      study. RESULTS: The mean score of hope and self-esteem among adolescents from
      authoritative parents were higher from permissive and authoritarian families
      while the hope with a permissive perception were lower than those with
      authoritarian, and self-esteem was lower in the authoritarian group compared to
      the permissive group. Children with a permissive perception reported higher
      psychoticism compared to the two other. Significant correlations were found
      between authoritative perception and hope, self-esteem and psychoticism. Finally,
      hope, self-esteem and psychoticism showed a significant inter correlation in all
      of the parental styles. CONCLUSION: Adolescents with the perception of each kind
      of parental style showed significant between group differences in psychological
      well-being throughout the four years of the study.

PMID- 23967425
TI  - Mapping the obesity in iran by bayesian spatial model.
AB  - BACKGROUND: One of the methods used in the analysis of data related to diseases,
      and their underlying reasons is drawing geographical map. Mapping diseases is a
      valuable tool to determine the regions of high rate of infliction requiring
      therapeutic interventions. The objective of this study was to investigate obesity
      pattern in Iran by drawing geographical maps based on Bayesian spatial model to
      recognize the pattern of the understudy symptom more carefully. METHODS: The data
      of this study consisted of the number of obese people in provinces of Iran in
      terms of sex based on the reports of non-contagious disease's risks in 30
      provinces by the Iran MSRT disease center in 2007. The analysis of data was
      carried out by software R and Open BUGS. In addition, the data required for the
      adjacency matrix were produced by Geo bugs software. RESULTS: The greatest
      percentage of obese people in all age ranges (15-64) is 17.8 for men in
      Mazandaran and the lowest is 4.9 in Sistan and Baluchestan. For women the highest
      and lowest are 29.9 and 11.9 in Mazandaran and Hormozgan, respectively.
      Mazandaran was considered the province of the greatest odds ratio of obesity for
      men and women. CONCLUSION: Recognizing the geographical distribution and the
      regions of high risk of obesity is the prerequisite of decision making in
      management and planning for health system of the country. The results can be
      applied in allocating correct resources between different regions of Iran.

PMID- 23967426
TI  - Descriptive Aspects of Injection Drug Users in Iran's National Harm Reduction
      Program by Methadone Maintenance Treatment.
AB  - BACKGROUND: The Ministry of Health, Treatment and Medical Education of Iran has
      recently announced an estimated figure of 200,000 injecting drug users (IDUs).
      The aim of this study was to pilot a national program using demographics, types
      of drug abuse and prevalence of blood-borne infections among IDUs. METHODS: In
      order to elicit data on demographics, types of drug abuse and prevalence of blood
      borne infections among IDUs, a questionnaire was designed in the Bureau of Mental
      Social Health and Addiction in collaboration with Iran's Drug Control
      Headquarters of the Police Department. Therapeutical alliance of addiction in
      Shafagh Center was based on Methadone Maintenance Therapy (MMT). RESULTS: Among
      402 reported IDUs most of them were male, single and in age range of 20 to 39
      years old with 72.7% history of imprisonment. Most of them had elementary and
      high school education and a history of addiction treatment. The majority were
      current users of opioid, heroin and crack. The prevalence of blood-borne
      infections was 65.9% and 18.8% for HCV and HIV/AIDS infections, respectively.
      CONCLUSION: Prevention programs about harm reduction, treatment and counseling
      should include young IDUs as a core focus of their intervention structure.

PMID- 23967427
TI  - Reporting of Ethical Considerations Associated with Clinical Trials Published in
      Iranian Dental Journals between 2001 and 2011.
AB  - BACKGROUND: Ethical consideration is a basic requirement for design of randomized
      clinical trials. The purpose of this study was to assess whether reports of
      Iranian dental clinical trials complied with the requirements of the ethical
      principles of human research. METHODS: In this retrospective observational study
      electronic search was performed to identify all dental clinical trials published
      between 2001 and 2011. Each trial report was assessed for inclusion of a
      statement that 17 items about research ethics. RESULTS: Totally 242 papers were
      identified, of which 15.3%, stated that ethical approval had been obtained and
      50.4% of the trial reports indicated that informed consent had been obtained. The
      mean ethical score for the mentioned studies was 7/68 out of 17. CONCLUSIONS:
      Most Iranian dental clinical trial reports failed to consider important ethical
      principles. The reporting of the ethical issues associated with these trials
      could be improved further not only by the instructions to authors, but also by
      Journal editors refusing to publish trials that do not comply.

PMID- 23967428
TI  - Brewer's Yeast Improves Blood Pressure in Type 2 Diabetes Mellitus.
AB  - BACKGROUND: This study was conducted to investigate the effects of Brewer's yeast
      supplementation on serum lipoproteins and blood pressure in patients with Type 2
      diabetes mellitus. METHODS: In a randomized double blind clinical trial, 90
      adults with type 2 diabetes mellitus were recruited, and divided randomly into 2
      groups, trial group received brewer's yeast (1800 mg/day) and control group
      received placebo for 12 weeks. Weight, BMI, food consumption (based on 24 hour
      food recall), fasting serum lipoproteins (Cholesterol, Triglyceride, LDL-c, HDL
      c), systolic and diastolic blood pressures were measured before and after the
      intervention. Data analyses were performed by Statistical Package for Social
      Sciences ver. 18.0, and the statistical tests included Independent t-test, Paired
      t-test, Kolmogorov-Smirnov and analysis of covariance. This trial was registered
      in Iranian Registry of Clinical Trials (IRCT), No.IRCT138807062513N1. RESULTS:
      Eighty-four subjects (21 men and 63 women) aged 46.3+/-6.1 years completed the
      study. After 12 weeks supplementation, systolic and diastolic blood pressures
      were decreased in the group receiving brewer's yeast (4.1+/-1.5, P=0.007 and
      5.7+/-0.6, P=0.001 respectively). No-significant changes in LDL-c, HDL-c,
      Triglyceride and Cholesterol were shown. CONCLUSION: Supplementation with
      Brewer's yeast besides the usual treatment of type 2 diabetes mellitus can reduce
      systolic and diastolic blood pressures in diabetic patients.

PMID- 23967429
TI  - Parallel quality assessment of emergency departments by European foundation for
      quality management model and Iranian national program for hospital evaluation.
AB  - BACKGROUND: European Foundation for Quality Management (EFQM) model is a widely
      used quality management system (QMS) worldwide, including Iran. Current study
      aims to verify the quality assessment results of Iranian National Program for
      Hospital Evaluation (INPHE) based on those of EFQM. METHODS: This cross-sectional
      study was conducted in 2012 on a sample of emergency departments (EDs) affiliated
      with Tehran University of Medical Sciences (TUMS), Iran. The standard
      questionnaire of EFQM (V-2010) was used to gather appropriate data. The results
      were compared with those of INPHE. MS Excel was used to classify and display the
      findings. RESULTS: The average assessment score of the EDs based on the INPHE and
      EFQM model were largely different (i.e. 86.4% and 31%, respectively). In
      addition, the variation range among five EDs' scores according to each model was
      also considerable (22% for EFQM against 7% of INPHE), especially in the EDs with
      and without prior record of applying QMSs. CONCLUSION: The INPHE's assessment
      results were not confirmed by EFQM model. Moreover, the higher variation range
      among EDs' scores using EFQM model could allude to its more differentiation power
      in assessing the performance comparing with INPHE. Therefore, a need for
      improvement in the latter drawing on other QMSs' (such as EFQM) strengths, given
      the results emanated from its comparison with EFQM seems indispensable.

PMID- 23967430
TI  - Molecular Genotyping of Toxoplasma gondii in Human Spontaneous Aborted Fetuses in
      Shiraz, Southern Iran.
AB  - BACKGROUND: Congenital toxoplasmosis is associated with variable complications
      including encephalitis, microcephaly, hydrocephaly, hepatitis, lymphadenopathy
      and even intrauterine death. Presence of Toxoplasma gondii in human placenta may
      induce congenital infection. The aim of this study was to determine the genotypes
      of Toxoplasma gondii infection in human spontaneous aborted fetuses in Shiraz,
      south of Iran. METHODS: Five hundred and forty two paraffin-embedded blocks of
      aborted placenta were collected, from two university-affiliated hospitals in
      Shiraz. Occurrence of spontaneous abortion was confirmed by examine of the
      slides. After re-cutting of the blocks and dewaxing, semi-nested PCR assay was
      used to detect the fragments of T. gondii B1 gene in the samples. Also direct
      molecular genotyping was performed on positive samples with Restriction Fragment
      Length Polymorphism-PCR analysis on the SAG2 gene. RESULTS: Among the 542 tissue
      samples, the B1 gene was amplified from 78 (14.4%) of cases with the semi nested
      PCR and typed by RFLP. The genotype of Toxoplasma strains of 65 (out of 78) PCR
      positive samples were evaluated and 54 out of 65 (83.1%) were found to be type II
      and 11 out of 65 (16.9%) were type I. CONCLUSION: Considering the high level of
      Toxoplasma infection in aborted fetuses in this study, Toxoplasma might largely
      contribute to spontaneous abortion in this area of Iran.

PMID- 23967431
TI  - Antenatal Micronutrient Supplementation Relationship with Children's Weight and
      Height from Birth up to the Age of 18 Months.
AB  - BACKGROUND: Maternal nutritional is the most important environmental factor
      influencing pregnancy outcome. While studies showed association between maternal
      iron-micronutrient deficiencies with pregnancy outcome, data examining impact of
      micronutrient supplementation on growth rate beyond birth are sparse. Present
      study examined the relationship between iron and multivitamins supplementation on
      growth rate of babies up to age of 18 month. METHODS: This study was a
      statistical analysis on data recorded through a routine procedure in health
      houses from 1994 to 2007. Subjects were selected by a two-stage randomization
      method and required data extracted from the records. Analyses were performed
      using STATA 10 software. RESULTS: Data was collected for 3835 pairs of mother
      baby. Mothers received 61.7+/-5.4 and 115.6+/-53.8 multivitamins and iron
      tablets, respectively. Analyses showed significant relationship between
      children's weight and height at birth with iron supplementation and children's
      height at 6, 12 and 18 month with multivitamins supplementation. CONCLUSIONS:
      Mechanisms of these effects are unclear but it is safe to suggest supplementation
      during pregnancy is necessary.

PMID- 23967432
TI  - Higher education initiatives for disaster and emergency health in iran.
AB  - Iran's health system is expanding the disaster and emergency higher education
      programs over the country to enhance the capacity of human resources for
      effective and efficient disaster mitigation, preparedness, response and recovery.
      In this article we present an overview about the initiatives and progress of
      disaster and emergency health higher education in Iran. Following the Bam
      earthquake, in collaboration with the Ministry of Health & Medical Education and
      National Institute of Health Research, School of Public Health at the Tehran
      University of Medical Sciences, Iran took the initiative to develop a Master of
      Public Health (MPH) with disaster concentration in 2006, a PhD in disaster and
      emergency health in 2011, and a well constructed certificate course in 2008
      entitled Disaster Health Management and Risk Reduction (DHMR). Iran, Kerman and
      Shahid Beheshti Universities of Medical Sciences and University of Social Welfare
      and Rehabilitation are other academia that joined this initiative. Regarding the
      importance of programs evaluation, we have planned for a comprehensive evaluation
      of MPH and DHMR programs in 2013-4 and the Accreditation and Evaluation Board of
      Disaster & Emergency Health, based in MOH&ME, is responsible for evaluation of
      the PhD program in 3-5 years from initiation. 

PMID- 23967433
TI  - Number of family members, a new influencing factor to affect the risk of melamine
      associated urinary stones.
AB  - Melamine is a new risk of urinary stones. Gansu province is a heavily affected
      area and has large population and underdeveloped economy. We hypothesized that
      number of family members and family income may play significant roles in the
      formation of urinary stones. A case-control study was performed among 190
      infants. Results showed that the case group had less numbers of family members
      than the control (4.4 vs. 5.6, respectively). The multivariate logistic
      regression analysis indicated that number of family members was an independent
      influencing factor associated with urinary stones (OR, 0.606; 95% CI, 0.411
      0.893; P = 0.011). Family income, however, did not exhibit a significant
      difference. Observed results suggested that number of family members was a new
      and significant influencing factor to affect the risk of melamine-associated
      urinary stones. 

PMID- 23967434
TI  - Increasing international divorce and decreasing international marriage in South
      Korea.

PMID- 23967435
TI  - Historical Issues of Optic neuritis and Sensory Disorder in Persian Traditional
      Medicine.

PMID- 23967436
TI  - Ergogenic AIDS use in Iranian adolescents.

PMID- 23967437
TI  - Liver- Heart Inter- Relationship in Fatty Liver Disease Based on the Avicenna's
      Point of View.

PMID- 23967438
TI  - The Death of Lichtenstein Hernioplasty under Local Anesthesia in China.

PMID- 23967439
TI  - The morphologic spectrum of cutaneous sarcoidosis.

PMID- 23967440
TI  - An approach to vasculitis and vasculopathy.
AB  - My approach to vasculitis and vasculopathy includes: (1) Determine the level of
      care the patient needs. If I am not sure, I will order a basic laboratory
      evaluation while I decide on the more specific laboratory tests to order and of
      course do a skin biopsy. (2) Determine if the eruption represents vasculitis or
      vasculopathy. The presence of livedo reticularis or retiform purpura points
      toward vasculopathy, but keep in mind the overlap, especially with the ANCA
      associated vasculitides. (3) If vasculitis, rule out the secondary causes (ie,
      infection, drug reactions, malignancy, connective-tissue disorders) first. (4)
      Determine the size of the vessel involvement and the organ systems involved,
      which will narrow down the differential diagnosis. Although no one approach works
      for everyone, I find this method to be simple and keeps you organized when
      tackling the workup of vasculitis and vasculopathy.

PMID- 23967441
TI  - An introduction to the mock boards for incoming residents.

PMID- 23967442
TI  - Treatment of actinic keratoses.

PMID- 23967443
TI  - A novel tridentate bis(phosphinic acid)phosphine oxide based europium(III)
      selective Nafion membrane luminescent sensor.
AB  - A new europium(III) membrane luminescent sensor based on a new tridentate
      bis(phosphinic acid)phosphine oxide (3) system has been developed. The synthesis
      of this new ligand is described and its full characterization by NMR, IR and
      elemental analyses is provided. The luminescent complex formed between
      europium(III) chloride and ligand 3 was evaluated in solution, observing that its
      spectroscopic and chemical characteristics are excellent for measuring in polymer
      inclusion membranes. Included in a Nafion membrane, all the parameters (ligand
      and ionic additives) that can affect the sensitivity and selectivity of the
      sensing membrane as well as the instrumental conditions were carefully optimized.
      The best luminescence signal (lambdaexc = 229.06 nm and lambdaem = 616.02 nm) was
      exhibited by the sensing film having a Nafion : ligand composition of 262.3 : 0.6
      mg mL(-1). The membrane sensor showed a short response time (t95 = 5.0 +/- 0.2
      min) and an optimum working pH of 5.0 (25 mM acetate buffer solution). The
      membrane sensor manifested a good selectivity toward europium(III) ions with
      respect to other trivalent metals (iron, chromium and aluminium) and
      lanthanide(III) ions (lanthanum, samarium, terbium and ytterbium), although a
      small positive interference of terbium(III) ions was observed. It provided a
      linear range from 1.9 * 10(-8) to 5.0 * 10(-6) M with a very low detection limit
      (5.8 * 10(-9) M) and sensitivity (8.57 * 10(-7) a.u. per M). The applicability of
      this sensing film has been demonstrated by analyzing different kinds of spiked
      water samples obtaining recovery percentages of 95-97%.

PMID- 23967445
TI  - [Pain memory--can we forget chronic pain?].

PMID- 23967444
TI  - Optimizing the synthesis of red- and near-infrared CuInS2 and AgInS2
      semiconductor nanocrystals for bioimaging.
AB  - This work reports the study of optimization of the reaction parameters on the
      synthesis of high quality CuInS2 and AgInS2 nanocrystals for bioimaging
      applications. The concentration of reaction precursors (e.g. Ag, Cu, In and S)
      plays a key role in determining the emission profile of these ternary quantum
      dots (QDs). By carefully varying the precursor compositions, the emission of QD
      can be tuned from red to near infrared (NIR) region. Taking the advantages of NIR
      emission, which possesses minimal absorption in biological tissues, we have also
      prepared water-dispersible CuInS2/ZnS and AgInS2/ZnS nanocrystals and
      demonstrated the high biocompatibility for both deep tissue penetration and tumor
      targeting. The QDs were stabilized in Pluronic F127 block copolymer micelles,
      offering us optically and colloidally stable contrast agents for in vitro and in
      vivo imaging. Two-photon excitation of QD has also been demonstrated,
      accomplishing a NIR-to-NIR transaction. This study devotes the key steps in
      promoting the use of ternary QDs as low-toxic, photostable, and cadmium-free
      semiconductor nanocrystal formulation for multiple imaging applications. 

PMID- 23967446
TI  - [The most important aspects of risk assessment].

PMID- 23967447
TI  - [Leakage of the right main bile duct].

PMID- 23967448
TI  - [Inter-culture aspects of the health sector: opportunities, risks and side
      effects].

PMID- 23967449
TI  - Effect of pan-retinal photocoagulation treatment on vision-related quality of
      life of patients with proliferative diabetic retinopathy.

PMID- 23967450
TI  - Role of hyperglycemia-mediated erythrocyte redox state alteration in the
      development of diabetic retinopathy.

PMID- 23967451
TI  - Selection on QTL and complex traits in complex environments.
AB  - Understanding genetic variation for complex traits in heterogeneous environments
      is a fundamental problem in biology. In this issue of Molecular Ecology, Fournier
      Level et al. (2013) analyse quantitative trait loci (QTL)influencing ecologically
      important phenotypes in mapping populations of Arabidopsis thaliana grown in four
      habitats across its native European range. They used causal modelling to quantify
      the selective consequences of life history and morphological traits and QTL on
      components of fitness. They found phenology QTL colocalizing with known flowering
      time genes as well as novel loci. Most QTL influenced fitness via life history
      and size traits, rather than QTL having direct effects on fitness.Comparison of
      phenotypes among environments found no evidence for genetic trade-offs for
      phenology or growth traits, but genetic trade-offs for fitness resulted because
      flowering time had opposite fitness effects in different environments. These
      changes in QTL effects and selective consequences may maintain genetic variation
      among populations.

PMID- 23967452
TI  - Urban behavioural adaptation.
AB  - A large and growing proportion of the world is impacted directly by human
      activities; among the most extreme of these is the spread of urban environments.
      Environmental change associated with urbanization represents a potentially potent
      source of selection. While urban environments generally have lowered
      biodiversity, some clades seem to thrive in urban settings. For example, many
      members of the bird family Turdidae, known as the 'truethrushes' and the
      blackbird Turdus merula (Fig. 1) in particular, are familiar urban species.
      Indeed, the colonization of urban environments by blackbirds has become a
      textbook case study for our understanding of the many ways a wild species can
      deal with urbanization. In this issue, Mueller et al. (Molecular Ecology, 00,
      2013, 00) add to that story by beginning to address the genetic nature of
      behavioural adaptation of blackbirds colonizing urban areas. They do this by
      testing for divergence between paired urban and rural samples at a suite of
      candidate genes with hypothesized effects on behaviours thought to be important
      for the colonization of urban environments.They find evidence for consistent
      patterns of divergence at an exonic microsatellite associated with the SERT gene.
      SERT has a number of hypothesized behavioural effects, including harm avoidance,
      which may be associated with tolerating the hustle and bustle of urban
      environments. This is among the first evidence that behavioural differences
      between urban and rural environments have a genetic basis and this work suggests
      that urban environments can in some cases exert homogeneous selection pressures.

PMID- 23967453
TI  - A deep dig--hindsight on Holocene vegetation composition from ancient
      environmental DNA.
AB  - Want a glimpse at past vegetation? Studying pollen and other plant remains, which
      are preserved for example in lake sediments or mires for thousands of years,
      allows us to document regional occurrences of plant species over radiocarbon
      dated time series. Such vegetation reconstructions derived from optical analyses
      of fossil samples are inherently incomplete because they only comprise taxa that
      contribute sufficient amounts of pollen, spores, macrofossil or other evidences.
      To complement optical analyses for paleoecological inference, molecular markers
      applied to ancient DNA (aDNA) may help in disclosing information hitherto
      inaccessible to biologists. Parducci et al. (2013) targeted aDNA from sediment
      cores of two lakes in the Scandes Mountains with generic primers in a meta
      barcoding approach. When compared to palynological records from the same cores,
      respective taxon lists show remarkable differences in their compositions, but
      also in quantitative representation and in taxonomic resolution similar to a
      previous study (Jorgensen et al. 2012). While not free of assumptions that need
      critical and robust testing, notably the question of possible contamination, this
      study provides thrilling prospects to improve our knowledge about past vegetation
      composition, but also other organismic groups, stored as a biological treasure in
      the ground.

PMID- 23967454
TI  - What is a genome?
AB  - The field of genomics is expanding rapidly, yet the meanings of the word 'genome'
      have yet to be conceptualized in explicit, coherent and useful frameworks. We
      develop and apply an evolutionary conceptualization of the genome,which
      represents a logical extension of the evolutionary definition of a gene developed
      by George C.Williams. An evolutionary genome thus represents a set of genetic
      material, in a lineage, that due to common interests tends to favour the same or
      similar phenotypes.This conceptualization provides novel perspectives on genome
      functions, boundaries and evolution, which should help to guide theoretical and
      empirical genomics research.

PMID- 23967455
TI  - The number of markers and samples needed for detecting bottlenecks under
      realistic scenarios, with and without recovery: a simulation-based study.
AB  - Detecting bottlenecks is a common task in molecular ecology. While several
      bottleneck detection method sexist, evaluations of their power have focused only
      on severe bottlenecks (e.g. to Ne ~10). As a component of a recent review, Peery
      et al. (2012) analysed the power of two approaches, the M-ratio and heterozygote
      excess tests, to detect moderate bottlenecks (e.g. to Ne ~100),which is realistic
      for many conservation situations. In this Comment, we address three important
      points relevant to but not considered in Peery et al. Under moderate bottleneck
      scenarios, we test the (i) relative advantage of sampling more markers vs. more
      individuals, (ii) potential power to detect the bottleneck when utilizing dozens
      of microsatellites (a realistic possibility for contemporary studies) and (iii)
      reduction in power when post bottle neck recovery has occurred. For the realistic
      situations examined,we show that (i) doubling the number of loci shows equal or
      better power than tripling the number of individuals,(ii) increasing the number
      of markers (up to 100) results in continued additive gains in power, and
      (iii)recovery after a moderate amount of time or gradual change in size reduces
      power, by up to one-half. Our results provide a practical supplement to Peery et
      al. and encourage the continued use of bottleneck detection methods in the
      genomic age, but also emphasize that the power under different sampling schemes
      should be estimated,using simulation modelling, as a routine component of
      molecular ecology studies.

PMID- 23967456
TI  - More precisely biased: increasing the number of markers is not a silver bullet in
      genetic bottleneck testing.
AB  - In response to our review of the use of genetic bottleneck tests in the
      conservation literature (Peery et al. 2012,Molecular Ecology, 21, 3403-3418),
      Hoban et al. (2013, Molecular Ecology, in press) conducted population genetic
      simulations to show that the statistical power of genetic bottleneck tests can be
      increased substantially by sampling large numbers of microsatellite loci, as they
      suggest is now possible in the age of genomics. While we agree with Hoban and co
      workers in principle, sampling large numbers of microsatellite loci can
      dramatically increase the probability of committing type 1 errors(i.e. detecting
      a bottleneck in a stable population) when the mutation model is incorrectly
      assumed. Using conservative values for mutation model parameters can reduce the
      probability of committing type 1 errors, but doing so can result in significant
      losses in statistical power. Moreover, we believe that practical limitations
      associated with developing large numbers of high-quality microsatellite loci
      continue to constrain sample sizes, a belief supported by a literature review of
      recent studies using next generation sequencing methods to develop microsatellite
      libraries. conclusion, we maintain that researchers employing genetic bottleneck
      tests should proceed with caution and carefully assess both statistical power and
      type 1 error rates associated with their study design.

PMID- 23967457
TI  - [Not Available].

PMID- 23967458
TI  - [Not Available].

PMID- 23967459
TI  - [Not Available].

PMID- 23967460
TI  - [Not Available].

PMID- 23967461
TI  - [Not Available].

PMID- 23967462
TI  - [Not Available].

PMID- 23967463
TI  - [Not Available].

PMID- 23967464
TI  - [Mammary carcinoma -18F-FDG-PET-CT-staging vs. conventional staging].

PMID- 23967465
TI  - [Symptomatic uterine fibroids - ultrasonic ablation of uterine fibroids].

PMID- 23967466
TI  - Authors' reply.

PMID- 23967467
TI  - Infusion pump integration.
AB  - A very small but growing number of hospitals have begun integrating their
      infusion pumps with their information systems and patient records. integrating
      your pumps can dramatically reduce infusion-related medication errors. But there
      are a number of significant barriers. Find out how the three main approaches to
      integration work, and learn some best practices for tackling the challenges.

PMID- 23967468
TI  - Vital signs monitors.
AB  - The VSi, VS2+, and VS4 vital signs monitors are the newest members of the Philips
      SureSigns family. Our testing shows that they have a number of advantages. A
      major concern, however, is that vitals data could be associated with the wrong
      patient I.D. if the user deviates from the recommended workflow. Read our
      complete findings and judgments.

PMID- 23967469
TI  - Disinfection cap cuts health system's central-line bloodstream infection rate in
      half.

PMID- 23967470
TI  - Common workarounds for EHRs suggest system limitations.

PMID- 23967471
TI  - Large study finds CT increases cancer risk for young patients.

PMID- 23967473
TI  - Max airway pressure alarm will not limit airway pressure in CareFusion 3100A high
      frequency oscillatory ventilators.

PMID- 23967472
TI  - New CDC guidelines outline four "E's" for injection safety.

PMID- 23967474
TI  - Rubber central axis cable cover on Trumpf ceiling-mounted system with monitor
      bracket may fall into the sterile field.

PMID- 23967475
TI  - Olympus ESG-100 footswitch can unexpectedly change ESU mode.

PMID- 23967477
TI  - Current world literature. Nosocomial and healthcare related infections.

PMID- 23967476
TI  - From the archives.

PMID- 23967478
TI  - Sharing blueprints for better research.

PMID- 23967479
TI  - The author file:  Chris Toumazou.

PMID- 23967480
TI  - Multidimensional data.

PMID- 23967481
TI  - Imaging: Embryos under the X-ray.

PMID- 23967482
TI  - Model organisms: Fly walk.

PMID- 23967483
TI  - Proteomics: Matching marks with mechanisms.

PMID- 23967484
TI  - Stem cells: Human stem cells from cloned embryos.

PMID- 23967485
TI  - Proteomics:   Peptides aplenty.

PMID- 23967486
TI  - Microbiology:   Assembling genomes in microbial communities.

PMID- 23967487
TI  - [SEPAR-ALAT consensus for inhaled therapies].

PMID- 23967488
TI  - Reply to S.P.Sura et al.

PMID- 23967489
TI  - Reply to M.-E. Percival et al and L.B. Saltz.

PMID- 23967490
TI  - Reply to M.-E. Percival et al and L.B. Saltz.

PMID- 23967491
TI  - Reply to Y.Yamamoto et al.

PMID- 23967492
TI  - Reply to L.Antonuzzo et al.

PMID- 23967493
TI  - Resistance exercise interventions during and following cancer treatment: a
      systematic review.
AB  - Findings from prior systematic reviews suggest that exercise results in
      meaningful improvements in many clinically relevant physiologic and quality of
      life (QOL) outcomes during and following cancer treatment. However, the majority
      of exercise-cancer studies have focused upon the benefits of aerobic exercise
      (AE) and knowledge of the efficacy of resistance exercise (RE) alone as a
      supportive care intervention for cancer patients and survivors remains limited.
      Consequently, the purpose of this review was to provide the first systematic
      evaluation of the effects of RE alone upon clinically relevant physiologic and
      QOL outcomes during and following cancer treatment. Literature searches were
      conducted to identify studies examining RE interventions in cancer patients and
      survivors. Data were extracted on physiologic (fitness, physical function, and
      body composition) and QOL (fatigue, psychological well-being, and cancer-specific
      and global QOL outcomes. Cohen's d effect sizes were calculated for each outcome.
      A total of 15 studies (6 in samples undergoing active cancer treatment and 9 in
      samples having completed cancer treatment) involving 1,077 participants met the
      inclusion criteria. Findings revealed that, on average, RE resulted in large
      effect-size improvements in muscular strength (d = 0.86), moderate effect-size
      improvements in physical function (d = 0.66), and small effect-size improvements
      in body composition (d = 0.28) and QOL (d = 0.25) outcomes. The effect sizes
      observed following RE are comparable in magnitude to the effects of exercise
      interventions reported in prior comprehensive reviews of the exercise-cancer
      literature which primarily focused upon AE. Additionally, the methodologic
      quality of the studies was generally strong. Taken collectively, results of this
      systematic review suggest that RE is a promising supportive care intervention
      that results in meaningful improvements in clinically relevant physiologic and
      QOL outcomes during and following cancer treatment.

PMID- 23967494
TI  - Predicting life expectancy in patients with advanced incurable cancer: a review.
AB  - Oncologists frequently face the difficult task of estimating prognosis in
      patients with incurable malignancies. Their prediction of prognosis informs
      decision-making ranging from recommendations of cancer treatments to hospice
      enrollment. Unfortunately, physicians' estimates of prognosis are often
      inaccurate and overly optimistic. Further, physicians often fail to disclose
      their prognosis estimates, despite patient wishes to the contrary. Several
      studies have examined patient factors that might improve physicians' prognostic
      accuracy, including performance status, clinical symptoms and laboratory values.
      Prognostic models have been developed and validated but, to date, none are able
      to provide accurate estimates throughout the spectrum of advanced illness. This
      review examines tools utilized to predict life expectancy for patients with
      advanced, incurable cancer.

PMID- 23967496
TI  - Palliative care training and associations with burnout in oncology fellows.
AB  - BACKGROUND: Burnout among physicians can lead to decreased career satisfaction,
      physical and emotional exhaustion, and increased medical errors. In oncologists,
      high exposure to fatal illness is associated with burnout. METHODS: The Maslach
      Burnout Inventory, measuring Emotional Exhaustion (EE), Depersonalization (DP),
      and Personal Accomplishment (PA), was administered to second-year US oncology
      fellows. Bivariate and multivariate analyses explored associations between
      burnout and fellow demographics, attitudes, and educational experiences. RESULTS:
      A total of 254 fellows out of 402 eligible US fellows responded (63.2%) and 24.2%
      reported high EE, 30.0% reported high DP, and 26.8% reported low PA. Over half of
      the fellows reported burnout in at least one domain. Lower EE scores were
      associated with the fellows' perceptions of having received better teaching,
      explicit teaching about certain end-of-life topics, and receipt of direct
      observation of goals-of-care discussions. Fellows who reported better overall
      teaching quality and more frequent observation of their skills had less
      depersonalization. Fellows who felt a responsibility to help patients at the end
      of life to prepare for death had higher PA. LIMITATIONS: This survey relies on
      the fellows' self-reported perceptions without an objective measure for
      validation. Factors associated with burnout may not be causal. The number of
      analyses performed raises the concern for Type I errors; therefore, a stringent P
      value (0.01) was used. CONCLUSIONS: Burnout is prevalent during oncology
      training. Higher-quality teaching is associated with less burnout among fellows.
      Fellowship programs should recognize the prevalence of burnout among oncology
      fellows as well as components of training that may protect against burnout.

PMID- 23967495
TI  - Caring for oneself to care for others: physicians and their self-care.
AB  - It is well known that clinicians experience distress and grief in response to
      their patients' suffering. Oncologists and palliative care specialists are no
      exception since they commonly experience patient loss and are often affected by
      unprocessed grief. These emotions can compromise clinicians' personal well-being,
      since unexamined emotions may lead to burnout, moral distress, compassion
      fatigue, and poor clinical decisions which adversely affect patient care. One
      approach to mitigate this harm is self-care, defined as a cadre of activities
      performed independently by an individual to promote and maintain personal well
      being throughout life. This article emphasizes the importance of having a self
      care and self-awareness plan when caring for patients with life-limiting cancer
      and discusses validated methods to increase self-care, enhance self-awareness and
      improve patient care.

PMID- 23967503
TI  - Canada Health Infoway's ImagineNation Outcomes Challenge announces recipients of
      Momentum Awards.

PMID- 23967497
TI  - South African guideline for the management of chronic hepatitis B: 2013.
AB  - Hepatitis B remains a significant yet preventable health issue in South Africa.
      The introduction of the hepatitis B vaccine into the country some 18 years ago
      has demonstrated benefit, but the exposure to, and prevalence of chronic HBsAg
      positivity remain unacceptably high. Those with chronic hepatitis B virus
      infection have an elevated risk of developing cirrhosis with end-stage liver
      disease and a markedly elevated risk of hepatocellular carcinoma, independent of
      the presence of cirrhosis. The challenge in South Africa remains prevention
      through the universal vaccination coverage of all children and the identification
      of those with chronic hepatitis B virus infection. Over the last decade our
      understanding of hepatitis B and its behaviour and natural history in those with
      chronic infection has significantly improved. This understanding is key to
      identifying those who warrant further evaluation and therapy. A number of global
      societies have updated their guidelines in recent years. This document draws on
      these guidelines and serves to contextualise, for South Africa, practice
      guidelines for the management of chronic hepatitis B.

PMID- 23967504
TI  - [Professional promotion of normal birth?].

PMID- 23967505
TI  - [Reply to the letter from Dr. Christine Loytved and Prof. Beate Schucking].

PMID- 23967506
TI  - [Interdisciplinary discourse about birth].

PMID- 23967507
TI  - [Reply to the letter from Mrs. Nancy Stone and Mrs. Angelica Ensel ].

PMID- 23967508
TI  - [Swing against suspended animation].

PMID- 23967510
TI  - Proceedings and abstracts of the 64th International Symposium on Crop Protection
      Part II, May 22, 2011. Gent, Belgium.

PMID- 23967509
TI  - [Infantile myofibromatosis].

PMID- 23967511
TI  - Proceedings and abstracts of the 64th International Symposium on Crop Protection
      Part I, May 22, 2011. Gent, Belgium.

PMID- 23967512
TI  - Proceedings of the Ninth International Symposium on Marek's disease and Avian
      Herpesviruses. June 24-28, 2012, Berlin, Germany.

PMID- 23967513
TI  - The strength of no association between diet quality indices and simple indices of
      overweight/obesity.

PMID- 23967514
TI  - Authors' reply.

PMID- 23967515
TI  - Festschrift for Hans-Jorg Rheinberger.

PMID- 23967516
TI  - Author reply: To PMID 23468437.

PMID- 23967517
TI  - Letter to the editor.

PMID- 23967518
TI  - [Research strategy for development of antineoplastic agents].

PMID- 23967519
TI  - Announcing a new continuing medical education course: "Bridging Neurology and
      Psychiatry: Movement Disorders".

PMID- 23967520
TI  - Instant result: Receive a health boost from the first minute you get moving.

PMID- 23967521
TI  - Share the health: Looking for a good home for your unwanted diabetes supplies?
      Here are some options.

PMID- 23967522
TI  - Age appropriate: Should seniors keep very tight glucose control? That's up for
      debate.

PMID- 23967523
TI  - Low places: How to cope with hypoglycemic episodes--even when they don't happen
      to you.

PMID- 23967524
TI  - Curves ahead: yoga is for every body.

PMID- 23967525
TI  - Many happy returns: Celebrating the 30th anniversary of the most influential
      diabetes study to date.

PMID- 23967526
TI  - Heart smarts: Studying the role of the autoimmune response in type 1 heart
      attacks.

PMID- 23967527
TI  - It is my honor to serve you. New ACHE CEO looking forward to building on
      traditions while embracing changes ahead.

PMID- 23967528
TI  - Balancing the cost structure: innovative approaches for long-term savings and
      high-quality care.

PMID- 23967529
TI  - Consolidation: challenges and opportunities. Considering partnership strategies
      for organizational sustainability.

PMID- 23967530
TI  - Ethics in clinical research. Executives must ensure trial participants'
      protection and the public's best interest.

PMID- 23967531
TI  - Post-discharge calls and improved satisfaction. Follow-up calls, other efforts
      improve patient experience, survey scores.

PMID- 23967532
TI  - A foundation of wellness. Hospitals can play a leadership role in improving the
      health status of their employees and community.

PMID- 23967533
TI  - Polarized views of reform fading to gray. Insurance exchanges, state-federal
      partnerships to be put to the test.

PMID- 23967534
TI  - The jobs of tomorrow. As the field ofhealthcare evolves, new career paths emerge.

PMID- 23967535
TI  - Governing for healthcare transformation: A CEO perspective. Trustee oversight
      will further partnerships in the care continuum.

PMID- 23967536
TI  - The leader's role in medical device safety. Healthcare executives must ensure
      appropriate policies, procedures.

PMID- 23967537
TI  - The search for quality and outcomes. Strategic physician alignment is key to
      improving care while reducing costs.

PMID- 23967539
TI  - Appropriate preparation for healthcare executive management positions for all new
      entrants to the field.

PMID- 23967538
TI  - The healthcare executive's role in fostering inclusion of LGBT patients and
      employees.

PMID- 23967540
TI  - Impaired healthcare executives.

PMID- 23967541
TI  - Recently, in Boston, the unthinkable happened.

PMID- 23967542
TI  - Fecal transplant for recurrent Clostridium difficile infection.
AB  - Clostridium difficile infection (CDI) results in clinical manifestations ranging
      from mild diarrhea to life-threatening pseudomembranous colitis. Infection is
      most often initiated by antimicrobial therapy which causes an imbalance in normal
      colonic microflora. The pathogenesis of C. difficile is predominantly controlled
      by the production of its two cytotoxins, A and B, which damage the intestinal
      mucosa. In recent years a nationwide increase in the rate of CDI has been noted
      as well as an increase in mortality, reduced initial response to antimicrobials,
      extended resolution time, and increased rates of recurrence. Traditional
      treatment includes administration of antimicrobials. Fecal microbiota transplant
      (FMT) is an alternative therapy for CDI that is effective and promising in
      multiple CDI relapse patients. This paper will provide an overview of CDI
      epidemiology, pathogenesis, diagnosis, and treatment, and explore the case of a
      53-year-old woman suffering from her sixth episode of CDI.

PMID- 23967543
TI  - Organizational culture of Mississippi hospitals as perceived by laboratory
      professionals.
AB  - From 2006 through 2008, patient safety events cost the Medicare program $8.9
      billion and were associated with 99,180 hospital deaths. Of the $2.5 trillion
      spent on healthcare in 2009, 2.3% or $57.5 million was spent on laboratory costs.
      Reduction of laboratory-associated errors to 3.4 errors per 1 million tests could
      save money and lives. The organizational culture of a facility has an impact on
      quality improvement implementation. Clinical laboratories in Mississippi were
      surveyed to determine the predominant culture type as perceived by the medical
      laboratory professionals. Of the 1200 surveys mailed to 90 facilities, 272 were
      returned complete. It was determined that although the individual participant
      return rate was 28.6%, 49 of the 90 hospitals or 54.4% of the Mississippi
      facilities were represented through one or more individual participant responses.
      The culture scores revealed the following distribution for the individual
      respondents: group/clan culture scores were predominant for 106 (39.0%),
      hierarchical culture scores for 94 (34.6%), rational/market culture scores for 36
      (13.2%), and developmental/adhocratic culture scores for 24 (8.8%) of the
      individual respondents. The remaining 12 (4.4%) individuals reported blended or
      codominant culture scores with 50% claiming a group/clan and hierarchical split.
      The consolidation of the data to represent the 49 healthcare institutions
      revealed a different distribution, with 24 (49%) as hierarchical culture, 22
      (44.9%) as group/clan culture, and 3 (6.1%) as rational/market culture.
      Mississippi hospital data parallels previous findings with either hierarchical or
      group being the predominant organizational culture.

PMID- 23967544
TI  - A novel approach to managing hemolyzed specimens.
AB  - Hemolyzed specimens continue to cost the laboratory time and money. However, the
      core laboratory at Georgia Regents Health System, Inc. has instituted a novel
      approach to managing this problem. The purpose of this study was to determine
      whether the laboratory's new approach had a significant impact on the turn-around
      time (TAT) and cost of processing hemolyzed and non-hemolyzed specimens in the
      laboratory. The investigators queried the laboratory information systems for
      hemolyzed and non-hemolyzed specimens categorized as routine or STAT from the
      core laboratory and calculated statistical differences between the groups with
      respect to TAT and cost.The investigators found a statistically significant
      difference in the time it takes to process STAT hemolyzed specimens versus non
      hemolyzed specimens with the new approach. Because of the new approach, hemolyzed
      specimens were actually processed as fast as, or faster than non-hemolyzed
      specimens in the core laboratory.

PMID- 23967545
TI  - Sedimentation by gravity stabilizes plasma glucose for up to 60 minutes.
AB  - OBJECTIVE: Glucose levels decrease in whole blood in vitro, but there are several
      methods that minimize the loss, including special tubes and ice. This study
      evaluated whether sedimentation by gravity in an upright position was a viable
      alternative. DESIGN: Lithium heparinized blood was collected from 20 individuals
      without a diagnosis of diabetes. The samples were allowed to sediment at ambient
      temperature and were tested in quadruplicate at 30 minute intervals. A Repeated
      Measures ANOVA compared the means of each time-point. RESULTS: Plasma glucose
      results were not statistically different between 30 minutes and 60 minutes after
      collection (p = 0.156). At 90 minutes after collection, glucose was significantly
      different than the initial glucose readings (p <0.001). Each reading thereafter
      also showed a statistically significant difference from the initial reading.
      CONCLUSIONS: Samples for glucose measurement are stable in lithium heparin for no
      longer than 60 minutes when held in an upright position prior to centrifugation.

PMID- 23967546
TI  - Robot-assisted laparoscopic surgery in patients with advanced ovarian cancer:
      Farghaly's technique.

PMID- 23967547
TI  - Barrel index of bulky cervical tumours and intrauterine fluid determined by MRI
      as additional prognostic factors for survival.
AB  - OBJECTIVE: to investigate whether morphologic characteristics determined by
      magnetic resonance imaging (MRI) can discriminate between bulky cervical tumours
      with a favourable or worse prognosis. MATERIALS AND METHODS: MRI examinations
      were performed in 24 patients with cervical cancer Stage >or= 1B2. The ratio
      between tumour width and length (barrel index: BI) and the presence of
      intrauterine fluid retention were related to survival in a multivariate
      regression analysis. RESULTS: BI and intracavital fluid were predictors of
      survival, independent from tumour diameter and other known important factors for
      survival. A cut-off value of 1.40 for the BI proved to be the best prognostic
      factor with respect to recurrence and death: the hazard ratios of BI > 1.40 as
      compared to BI <or= 1.40 were 18.9 (95% CI 2.8 to 125.6) for recurrent disease
      and 16.4 (95% CI 2.9 to 93.9) for death by cervical cancer. The hazard ratios of
      intracavital fluid retention were 73.6 (95% CI 5.3 to 1,016.4) and 48.1 (95% CI
      4.7 to 491.6) for recurrence and death, respectively. CONCLUSION: The morphologic
      characteristic BI and the presence or absence of intracavital fluid as determined
      by MRI might have predictive value for survival in patients with bulky cervical
      tumours.

PMID- 23967548
TI  - Analysis of failures and clinical outcome of advanced epithelial ovarian cancer
      in patients with microscopic residual disease at second-look reassessment
      following primary cytoreductive surgery and first-line platinum-based
      chemotherapy.
AB  - AIM: To assess the pattern of failure and survival of advanced ovarian cancer
      patients with microscopic residual disease at second-look following cytoreductive
      surgery and platinum-based chemotherapy. MATERIALS AND METHODS: Nine-five women
      were retrospectively analyzed. Residual disease after initial surgery was > one
      cm in 58 (61.1%) patients, first-line chemotherapy was paclitaxel/platinum-based
      in 70 (73.7%) patients, second-look findings showed no macroscopic residuum but
      positive random peritoneal biopsies and/or positive washing ("true" microscopic
      residual disease) in 79 (83.2%) patients, and a macroscopic residuum which was
      completely resected (converted complete response) in 16(16.8%) patients. RESULTS:
      Eight-one (85.2%) patients developed recurrent disease after a median time of 14
      months (range four to 51). The abdomen (29.6%) and the pelvis (28.4%) were the
      most common sites of failure. Two- and five-year survival after second-look were
      78.1% and 31.0%, respectively. The clinical and pathological features with
      prognostic relevance at presentation (age, histotype, and tumor grade), as well
      as type of first-line chemotherapy and treatment after second-look were not
      related to the clinical outcome. There was a trend for a better survival in
      patients with optimal primary cytoreduction compared with those with suboptimal
      primary cytoreduction (five-year survival = 42.7% vs 23.4%). There was no
      significant difference in survival between the converted complete responders and
      the patients with "true" microscopic residual disease. CONCLUSIONS: These data
      confirm the unsatisfactory clinical outcome of patients with microscopic residual
      disease after first-line chemotherapy and the limited benefit of second-look
      reassessment.

PMID- 23967549
TI  - Bioethical issues on the role of contemporary gynecologists concerning HPV
      vaccination.
AB  - Debate is heating up whether or not to require girls to be vaccinated against the
      human papillomavirus (HPV), a leading cause of cervical cancer (CC). Prolepsis
      against this plague is mainly focused on early detection with Pap test
      (screening) and recently with administrating HPV vaccines in youths. OBJECTIVE:
      To discuss the increased bioethical role of contemporary gynecologist in the
      young population, with the aim to contribute to the decrease of this malignancy.
      MATERIALS AND METHODS: The authors searched the web (data-warehouse: articles,
      forums, etc., and data-mining: sequence analysis and classification) for HPV
      vaccination and related bioethical issues. RESULTS: HPV vaccines have already
      caused debates on whether they must be mandatory and on whether they cause a
      pseudo-safeness mental state, making youths "forget" necessary annual Pap tests
      or even worse, urging them in promiscuity, resulting in an increased occurrence
      of CC. CONCLUSIONS: Greece, in order to appropriately apply the Constitutional
      Law 5 Section 5 (All persons have the right to the protection of their
      health...), needs to train contemporary gynecologists in adequate youth
      consultation and proper family approaches regarding HPV vaccination issues.
      Enhancing the gynecologist's role, vaccination's effectiveness (sensitivity and
      specificity) will be increased and on the other hand, a rule of social law will
      be established in the country.

PMID- 23967550
TI  - Clinical picture of infiltrating lobular carcinoma of the breast: an analysis of
      96 patients.
AB  - OBJECTIVE: The aim of this study was to present the clinical picture of
      infiltrating lobular carcinoma (ILC) of the breast. MATERIALS AND METHODS: A
      detailed analysis was performed for the group of 96 ILC patients subject to
      initial surgical treatment in the Krakow Branch of Centre of Oncology between
      1983 and 1996. The investigated group was selected out of 2,347 breast cancer
      patients treated during that period, based on re-examination of histologic
      specimens of the initial patient group. RESULTS: The following distinctive
      demographic and clinical features of ILC were found: average age of patients: 59
      years (37 - 83); average duration of pathological symptoms: five months; most
      frequent site of primary tumor: upper outer quadrant (54.2%); primary tumor
      Stage: I/II0 (64.6%), III0A (35.4%); tumor size in breast: up to five cm (69.8%),
      larger than five cm (30.2%); no axillary lymph nodes involvement in 51% of
      patients; multifocality of lesions in 10% of patients; contralateral disease
      occurrence in eight percent of patients; atypical pattern of distant metastases,
      e.g. gastrointestinal system, gynaecologic organs, and cerebral meninges.
      CONCLUSIONS: Based on this analysis as well as on literature reports, it was
      found that the fundamental differences between ILC and infiltrating ductal
      carcinoma (IDC) included demographic and clinical features as patient age,
      primary tumor size at diagnosis, incidence of multifocality and contralateral
      disease, sites of distant metastases, and histopathological status of axillary
      lymph nodes.

PMID- 23967551
TI  - P16 immunostaining and HPV testing in histological specimens from the uterine
      cervix.
AB  - BACKGROUND: The cellular tumor suppressor protein pl61NK4a (p16) has been
      identified as a biomarker for transforming human papilloma virus (HPV)
      infections. P16 is a cyclin-dependent kinase inhibitor that regulates the cell
      cycle and cell proliferation by inhibiting cell cycle G1 progression. PURPOSE OF
      THE STUDY: To confirm the role of p16 as biomarker for transforming HPV
      infections and possible clinical applications in histological samples from the
      uterine cervix. MATERIALS AND METHODS: The subject of this study included 56
      biopsies of the cervical canal collected from January 2012 to September 2012 in
      the Institute of Pathology of the University of Sassari. The search for HPV
      immunohistochemistry was performed with the monoclonal antibody DAKO 1:25, while
      for the detection of p16 was used CINtecTM p16 (INK4a) histology kit. RESULTS: In
      56 biopsies performed in women aged between 23 and 69 years, the authors
      highlighted, by histological analysis, 24 cases of low-grade squamous
      intraepithelial lesion (LSIL) - cervical intraepithelial neoplasia (CIN1) and 31
      cases of high-grade squamous intraepithelial lesion (HSIL) - CIN2/3); 15 CIN2, 14
      CIN3, and two cervical squamous cell carcinoma in situ (SCIS). One case was an
      infiltrating squamous cell carcinoma (ISC). In 24 CIN1, there was a 16.67%
      positivity for p16 and an equal percentage occurred for HPV. In 15 cases of CIN2
      the percentage of positivity for p16 was considerably increased (73.33%), unlike
      the search for HPV which had a positivity rate of 20%. Finally, in 14 cases of
      CIN3, and in three carcinomas, the positivity for p16 was equal to 100%, however
      the search for HPV positivity was between 0% and 7.14%. CONCLUSIONS: These
      results demonstrated that p16 was a highly sensitive marker of cervical
      dysplasia. The authors have shown that p16 overexpression increased with the
      severity of cytological abnormalities and that had a greater ability to identify
      the viral infection compared to the classical immunohistochemical staining for
      HPV.

PMID- 23967552
TI  - Laparoscopic surgical staging of endometrial cancer: does obesity influence
      feasibility and perioperative outcome?
AB  - AIM: Laparoscopic treatment of early-stage endometrial cancer is the gold
      standard to reduce perioperative morbidity. Obesity is a well-known risk factor
      for endometrial cancer and anesthesiological and surgical complications. The
      authors' aim was to examine the effect of body mass index (BMI) on perioperative
      parameters and complications in laparoscopically-treated patients with
      endometrial cancer. MATERIALS AND METHODS: A consecutive series of patients
      affected by endometrial cancer and their demographic and clinicopathological data
      were collected. Patients were divided in 41 non-obese (BMI <or= 29.9) and 34
      obese (BMI >or= 30) groups. All patients had been preoperatively evaluated with
      hysteroscopic procedures and toraco-abdominal computed tomography (CT) and had
      been submitted to laparoscopic radical hysterectomy according to Querleu-Morrow,
      pelvic lymphadenectomy, peritoneal washing, and bilateral adnexectomy. RESULTS:
      There was no statistically significant difference in blood loss, number of lymph
      nodes removed, and hospital stay between the groups, but there was a trend
      towards a lengthening of surgical time in the obese women. There were no major
      intraoperative and postoperative complications. DISCUSSION: This study
      demonstrates that laparoscopic approach is feasible and safe in obese women
      evaluating the anesthesiological risk.

PMID- 23967553
TI  - Multidisciplinary approach as the optimum for surgical treatment of
      retroperitoneal sarcomas in women.
AB  - INTRODUCTION: The study aimed at evaluating surgical treatment results of
      retroperitoneal sarcomas (RPS) in female patients in terms of urological and
      oncological-gynecological collaboration. MATERIALS AND METHODS: The authors
      performed a retrospective review of 17 women who underwent resection of a
      retroperitoneal tumor. The surgical results, complications, and both overall and
      disease-free survivals were evaluated. The assessment of a positive surgical
      margin and the size of the tumor were the second objective. The Kaplan-Meyer
      survival analysis was used for statistical evaluation. RESULTS: The median follow
      up was 60 (26 - 128) months. The mean age was 55.4 (35 - 75) years. The mean size
      of tumors was 14.8 (6 - 45) cm. Local recurrences were recorded in three
      patients, while distal metastases were reported in one patient. Two patients died
      of distal metastases. The overall and cancer-specific survival was 87.5% and
      disease-free survival was 76.5%. CONCLUSIONS: Complete resection is the only
      effective treatment of retroperitoneal sarcomas. Presence of positive surgical
      margin is connected with a high risk of local recurrence regardless of an
      adjuvant chemo-and radiotherapy. The size of tumor had no impact on the survival
      or risk of local recurrence in the study group. The uro-gynecological
      collaboration was evaluated as well-suited in this part of oncological surgery.

PMID- 23967554
TI  - Nestin expression as an indicator of cervical cancer initiation.
AB  - Nestin is an intermediate filament protein expressed in proliferating cells
      during embryonic development of the central nervous system (CNS) and considered
      to be a neuronal stem cell/progenitor cell marker. This study investigated the
      difference of nestin expression between pre-cancer (carcinoma in situ - CIS) and
      cancer of cervix in 129 tissues (49 normal cervix, 41 CIS, and 39 invasive
      cervical cancer) through the use of a paraffin-embedded tissue array.
      Immunostaining was evaluated by intensity, proportion of stained cells, and
      pattern of expression. The expression of nestin was positive in 63.4% (26/41) for
      CIS and 43.6% (17/39) for invasive cervical cancer, but only 26.5% (13/49) for
      normal tissues (p = 0.002). Strong positive staining/large proportion staining
      were 53.7% (22/41) / 36.6% (15/41), 15.4% (6/39) / 61.5% (24/39) in the CIS and
      invasive cervical cancer tissues, respectively (p = 0.043, p < 0.001). The
      diffuse stain with basal layer was positive in 90.2% (37/41) for CIS, but only
      24.5% (12/49) of the samples were positive in normal tissues (p < 0.001). Based
      on these results, the authors suggest that nestin expression seems to participate
      in the step of cancer initiation and could potentially be a useful marker in the
      early detection of cervical cancer.

PMID- 23967555
TI  - Morular endometrial metaplasia: review of the literature and proposal of the
      management.
AB  - PURPOSE OF INVESTIGATION: Morular endometrial metaplasia is a rare condition that
      can be often misdiagnosed and overtreated, because it can be mistaken for a
      malignant disease. The aim of this review was to update the current opinion on
      the significance of this pathology and its risk for potential malignancies.
      MATERIALS AND METHODS: The authors report their experience of two cases of
      morular metaplasia involving very young women managed conservatively with
      hysteroscopic resection of the affected areas. RESULTS: Hysteroscopic resection
      of these lesions can be an adequate and fertility-sparing treatment of morular
      metaplasia in women of childbearing age. CONCLUSIONS: Morular metaplasia has
      indeed a mutational origin but it is a benign and hormonally inert condition. The
      risk to develop cancer is closely associated with premalignant or malignant
      endometrioid glandular proliferations that are often associated with
      hysthological finding of morules rather than with morules themselves. Management
      of this condition requires trained pathologists and gynecologists and should be
      adapted to the age of the patient.

PMID- 23967556
TI  - The effects of simple and radical hysterectomy and radiotherapy on lower urinary
      tract symptoms and urodynamics.
AB  - PURPOSE: To evaluate effects of simple/radical hysterectomy, radiotherapy, and
      their combination on lower urinary tract symptoms (LUTS) and urodynamics.
      MATERIALS AND METHODS: Four groups were formed as simple hysterectomy; Group 1 (n
      = 20), Type-II hysterectomy; Group 2 (n = 11), Type-II hysterectomy +
      radiotherapy; Group 3 (n = 16), radiotherapy; Group 4 (n = 20). LUTS, bladder
      diary, pad test, Q-tip test, stress-test, urodynamics, bladder-wall-thickness
      measurement, King's Health Questionnaire (KHQ) performed prior and at six and 18
      months after treatment. RESULTS: Pre-treatment prevalence of LUTS was higher in
      Group 1 and decreased at six and 18 months. LUTS increased in Groups 2, 3, and 4
      at six months; some of the symptoms decreased to pre-treatment levels at 18
      months. Quality of life improved in Group 1 and worsened in the others. Maximum
      bladder capacity increased in Group 1 and decreased in Groups 2 and 3. Bladder
      wall-thickness, maximum detrusor pressures increased, urine sensation decreased
      in Groups 2 and 4. Maximum vesical pressure increased and compliance decreased in
      Groups 2 and 3. CONCLUSION: LUTS may decrease after simple hysterectomy. Radical
      hysterectomy and radiotherapy result in voiding dysfunction; however some of the
      symptoms may decrease to pre-treatment levels during follow-up.

PMID- 23967557
TI  - Immunohistochemical evaluation of epithelial antigen Ber-Ep4 and CD10: new
      markers for endometriosis?
AB  - BACKGROUND: Early and certain diagnoses of endometriosis are mandatory to begin
      the correct treatment and to exclude the risk of endometriosis-associated ovarian
      carcinoma (EOC) and endometrial stromal sarcoma (ESS). PURPOSE OF THE STUDY: To
      assess the immunohistochemical expression of Ber-Ep4, an epithelial antigen, and
      CD10 in endometriosis. MATERIALS AND METHODS: Forty-eight women underwent
      laparoscopic surgery for endometriosis and endometriotic samples were recovered
      for histology. In all surgical specimens Ber-Ep4 and CD10 were searched by an
      immnohistochemical method. The authors evaluated the correlations among the
      immunohistochemical positivity and the location of endometriosis. RESULTS: Most
      cases (40/48 83.34%) were represented by ovarian endometriotic cyst. Among the
      eight remaining cases, three (3/48, 6.25%) were pelvic endometriotic lesions, two
      (2/48, 4.17%) peritoneum of vesico-uterine pouch, one vaginal lesion (2.08%), one
      salpinx lesion (2.08%), and one inguinal location (2.08%). Ber-Ep4 and CD10 were
      expressed in 90% and in 100% of the ovarian lesions, respectively. In pelvic
      lesions Ber-Ep4 and CD10 showed both 66.67% of positivity and had the same
      pattern in peritoneal, salpinx, vaginal, and inguinal lesions (50%, 100%, 100%,
      100%, respectively). Ber-Ep4 was negative in 6/48 (12.5%) cases whereas CDO10 was
      negative in 2/48 (4.17%) cases of endometriosis. The sensitivity of Ber-Ep4 and
      CD10 for endometriosis diagnosis were 87.50% and 95.83%, respectively.
      Immunohistochemistry for Ber-Ep4 showed positivity in all cases of endometriosis
      with typical cubic epithelium, whereas CD10 was positive in 1/2 (50%) atypical
      case. CONCLUSION: Immunohistochemical expression of Ber-Ep4 and CD10 was positive
      in most cases of endometriosis and was useful in differential diagnosis with
      mesothelial cysts. Ber-Ep4 was negative in cases of hyperplastic epithelium or
      cytological atypia; these cases are not well-differentiated and could be
      optimally treated by surgery and not by hormonal therapy because of the risk of
      cancer degeneration.

PMID- 23967558
TI  - Prevalence and distribution of high-risk human papillomavirus genotypes in
      cervical carcinoma, low-grade, and high-grade squamous intraepithelial lesions in
      Jordanian women.
AB  - PURPOSE: To assess high-risk human papillomavirus (HR-HPV) prevalence, and
      genotype distribution in invasive cervical cancer (CC) and its precursors in
      Jordanian patients. MATERIALS AND METHODS: A total of 124 different specimens of
      formalin-fixed, paraffin embedded samples, including 18 low-grade squamous
      intraepithelial lesions (LSILs), 28 high grade squamous intraepithelial lesions
      (HSILs), and 78 CCs were included in this study. HPV detection and typing was
      done using HPV High Risk Typing Real-TM Kit that enables the concomitant
      detection of the 12 most common HR-HPVs. RESULTS: Overall, HR-HPV prevalence was
      87.2%, 78.6%, and 72.2% in CC, HSIL, and LSIL respectively. Genotype 16 was the
      most predominant in all cervical lesions, detected in 53.8%, 46.4%, and 38.9% of
      CC, HSIL, and LSIL, respectively. Among all HPV genotypes, HPV-16 and HPV-18 were
      found separately or together in 50% of LSILs, 60.7% of HSILs, and 76.9% of CC
      specimens. HPV-31 was the second most common type detected in LSILs (22.2%) and
      HSILs (21.4%). HPV-45 was the third most common type detected in CC (11.5%).
      CONCLUSION: The prevalence and genotypes distribution patterns of HR-HPV types
      among patients with CC and its precursors in Jordan are similar to known
      international patterns. The results of this study provide baseline information on
      the HPV type distribution, which may guide the development of CC prevention and
      control programs in Jordan.

PMID- 23967559
TI  - Left fallopian tube primitive serous adenocarcinoma presenting as a cardiac
      tamponade - a case report and review of literature.
AB  - A 61-year-old woman presented to the emergency room complaining of anterior left
      thoracic pain and shortness of breath even after minor efforts. Her previous
      medical history was unremarkable. Pulmonary angiographic tomography showed a
      moderate bilateral pleural effusion that had collapsed inferior lung lobes, a
      large pericardial effusion, and several enlarged lymph nodes in the anterior
      mediastinum. Echocardiogram (ECG) showed a considerable pericardial effusion with
      some degree of heart function impairment. Pericardiocentesis and thoracocentesis
      revealed neoplastic cells in both pericardial and pleural fluids. Abdominal and
      pelvic ultrasound showed a complex cystic mass with a 13-cm diameter located at
      left adnexal region and another complex cystic tumor with five-cm diameter at
      right adnexal region, with small amount of peritoneal effusion. Surgical staging
      was performed. Pathologic diagnosis was primitive left fallopian tube serous
      adenocarcinoma with peritubal involvement and multiple peritoneal and lymphatic
      metastases (FIGO Stage IV; TNM pT3c M1). Chemotherapy was initiated. Death
      occurred 25 months after diagnosis, with secondary dissemination (breast and
      lung). No recurrence of pericardial effusion was registered after chemotherapy,
      suggesting a high susceptibility of pericardial metastasis.

PMID- 23967560
TI  - Hemoperitoneum and acute abdomen caused by the rupture of ovarian granulosa cell
      tumor: a case report.
AB  - Granulosa cell tumors (GCT) constitute 70% of all ovarian sex-cord stromal
      tumors, which account for less than five percent of all ovarian carcinoma. The
      authors herein report a rare case of a ruptured GCT of the ovary in a 43-year-old
      female who was admitted to the emergency department with signs of acute abdomen.

PMID- 23967561
TI  - Late recurrence of malignant melanoma mimicking primary peritoneal cancer.
AB  - BACKGROUND: Malignant melanoma is an extremely malignant tumor with an
      unpredictable metastatic profile with variable periods of remission. CASE: A 41
      year-old woman presented with recurrent malignant melanoma which had clinical
      features of an acute state mimicking primary peritoneal cancer. The case was an
      unusual recurrence of malignant melanoma occurring seven years after diagnosis
      and treatment of malignant melanoma in the patient's arm. The diagnosis was
      established postoperatively by immunohistochemistry. CONCLUSION: A variety of
      imaging methods and pathological methods, including an exploratory laparotomy,
      may be necessary in cases of patients suspecting primary peritoneal cancer with a
      previous history of melanoma with possible metastatic dissemination. Urgent
      diagnosis and treatment of these patients seems to be critical.

PMID- 23967562
TI  - Amelanotic malignant melanoma of the perineum: a case report.
AB  - The case of a patient diagnosed and surgically treated for amelanotic malignant
      melanoma of the perineum, accompanied by several local relapses, metastases to
      iliac-femoral lymph nodes, and distant metastases to both lungs is presented.
      Survival, up to date, equals 12 years. Amelanotic malignant melanomas are very
      rare tumors. Perineal and perianal localization of these tumors is especially
      rare. References cite about 500 cases with survival limited to between six months
      and one year after diagnosis..

PMID- 23967563
TI  - Acute hemorrhage related to spontaneous rupture of an uterine fibroid: a rare
      case report.
AB  - The authors present smooth muscle tumors of uncertain malignant potential (STUMP)
      diagnosis and surgical management of a spontaneously-ruptured degenerated uterine
      fibroids. A 48-year-old nulliparous presented with a two-day history of abdominal
      pain, bloating, constipation, and menorrhagia. Within eight hours, her distress
      level increased. Computed tomography (CT) scanning of the abdomen showed a large,
      31 x 25 cm solid-cystic lesion. An emergency laparotomy was indicated. Surgery
      revealed approximately 2,000 cc of blood and a 30 cm degenerated uterine fibroid
      with a fundal rupture, cystic, and solid components extending to the lower pole
      of the liver. Pathology results noted mild nuclear atypia, six mitoses per ten
      high-power fields (hpf) and necrosis spread that was not coagulative with a STUMP
      diagnosis. STUMP presents a problematic group of uterine smooth muscle tumors for
      any clinician. In addition, STUMP can rarely cause acute complications like a
      rupture. Therefore, prompt diagnosis and effective management are important.

PMID- 23967564
TI  - Multiorgan thrombotic disorder in a young patient with primary antiphospholipid
      syndrome (APS) and ovarian tumor.
AB  - Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening condition
      with high mortality rate besides aggressive multimodal treatment. Underlying
      triggers of "thrombotic and cytokine storm" include pregnancy, inflammation,
      trauma, surgery, and infection. The authors present a case of a young female
      patient with primary antiphospholipid syndrome (APS) who was admitted to the
      hospital due to abdominal pain caused by ovarian tumor with elevated tumor
      markers. After the prophylactic anticoagulants and antibiotic treatment, surgery
      was performed. Suddenly after treatment, her clinical status deteriorated and she
      died regardless of intensive immunosupresive and anticoagulant therapy attempts.
      This condition requires all clinical awareness, timely diagnosis, and
      therapeutical approach, including a better understanding of the pathophysiology
      that leads to CAPS.

PMID- 23967565
TI  - Uterine tumor resembling ovarian sex cord tumor. Case report and review of
      literature.
AB  - A uterine tumor resembling an ovarian sex cord tumor (UTROSCT) shows a poly
      phenotypic immunophenotype with coexpression of epithelial, myoid, and sex cord
      markers, as well as hormone receptors. The authors present a case of a 59-year
      old multiparous woman admitted to the Institute of Gynecology and Obstetrics
      Clinical Centre of Serbia in January 2010 due to prolonged vaginal bleeding and
      abdominal discomfort. The vaginal ultrasound showed an enlarged uterus size of
      100 x 74 x 81 mm, with extended cavity with an unhomogenic content and myomas
      sized 54 x 69 mm located in fundus with secondary changes. She underwent
      abdominal hysterectomy with adnexectomy. Microscopic examination revealed
      submucosal uterine tumor with variabile histological organization that had
      anastomotic trabeculae with solid cellular grupations. Rare mitotic figures (2/10
      HPF) were found. Additional imunohistochemistry showed immunophenotype: the sex
      cord areas were positive for vimentin(++), aSMA(++), AE1/AE3(+), PR(+), and
      ER(+). The poly phenotypic immunophenotype can be useful in differential
      diagnosis from other neoplasms but also suggests an origin of UTROSCT from
      uncommitted stem cell enabling for multidirectional differentiation.

PMID- 23967566
TI  - A rare case of lymphangiomyomatosis treated with leuprolide acetate: five-years
      follow-up.
AB  - Lymphangiomyomatosis (LAM) is a rare and systemic disease that is characterized
      by the abnormal proliferation of smooth muscle-like cells in the lungs and along
      the axial lymphatic system. The authors herein present a rare case of LAM that
      was treated with long-term use of leuprolide acetate, a gonadotropin-releasing
      hormone analogue (GnRHa).

PMID- 23967567
TI  - Endometrial stromal sarcoma with intracaval extension at initial presentation.
AB  - Endometrial stromal sarcoma (ESS) is a rare uterine neoplasm. Tumor involvement
      of the large vessels is extremely rare. This is a case report of ESS with tumor
      invasion of the inferior vena cava at initial presentation.

PMID- 23967568
TI  - Habitat damage, marine reserves, and the value of spatial management.
AB  - The biological benefits of marine reserves have garnered favor in the
      conservation community, but "no-take" reserve implementation is complicated by
      the economic interests of fishery stakeholders. There are now a number of studies
      examining the conditions under which marine reserves can provide both economic
      and ecological benefits. A potentially important reality of fishing that these
      studies overlook is that fishing can damage the habitat of the target stock.
      Here, we construct an equilibrium bioeconomic model that incorporates this
      habitat damage and show that the designation of marine reserves, coupled with the
      implementation of a tax on fishing effort, becomes both biologically and
      economically favorable as habitat sensitivity increases. We also study the
      effects of varied degrees of spatial control on fisheries management. Together,
      our results provide further evidence for the potential monetary and biological
      value of spatial management, and the possibility of a mutually beneficial
      resolution to the fisherman-conservationist marine reserve designation dilemma.

PMID- 23967569
TI  - Quantifying the balance between bycatch and predator or competitor release for
      nontarget species.
AB  - If a species is bycatch in a fishery targeted at its competitor or predator, it
      experiences both direct anthropogenic mortality and indirect positive effects
      through species interactions. If the species involved interact strongly, the
      release from competition or predation can counteract or exceed the negative
      effects of bycatch. We used a set of two- and three-species community modules to
      analyze the relative importance of species interactions when modeling the overall
      effect of harvest with bycatch on a nontarget species. To measure the trade-off
      between direct mortality and indirect positive effects, we developed a "bycatch
      transition point" metric to determine, for different scenarios, what levels of
      bycatch shift overall harvest impact from positive to negative. Under strong
      direct competition with a targeted competitor, release from competition due to
      harvest leads to a net increase in abundance even under moderate levels of
      bycatch. For a three-species model with a shared obligate predator, the release
      from apparent competition exceeds direct competitive release and outweighs the
      decrease from bycatch mortality under a wide range of parameters. Therefore, in
      communities where a shared predator forms a strong link between the target and
      nontarget species, the effects of indirect interactions on populations can be
      larger than those of direct interactions. The bycatch transition point metric can
      be used for tightly linked species to evaluate the relative strengths of positive
      indirect effects and negative anthropogenic impacts such as bycatch, habitat
      degradation, and introduction of invasive species.

PMID- 23967570
TI  - Scenarios involving future climate and water extraction: ecosystem states in the
      estuary of Australia's largest river.
AB  - Management of natural resources, particularly water, increasingly requires that
      likely benefits of particular actions (e.g., allocating an environmental flow)
      are quantified in advance. Therefore, new techniques are required that enable
      those potential benefits to be objectively compared among competing options for
      management (e.g., compared to a "do nothing" scenario). Scenario modeling is one
      method for developing such an objective comparison. We used existing hydrologic,
      hydrodynamic, and ecosystem response models for a case study location, the
      Coorong, an inverse estuary in South Australia, to illustrate the potential for
      such scenario modeling to inform natural resource management. We modeled a set of
      12 scenarios that included different levels of water extraction, potential future
      climate change, and sea-level change, thereby enabling a comparison of the
      different drivers of possible future reductions in water availability in the
      Coorong. We discovered that potential future climate change combined with current
      extraction levels has the capacity to devastate the ecology of the Coorong, but
      also that much of the degradation could be averted by reducing upstream
      extractions of water. The inclusion of possible sea-level change had a surprising
      effect, whereby higher sea levels increased hydrodynamic connectivity between the
      Coorong's two lagoons. Increased hydrodynamic connectivity limited the occurrence
      of extremely low water levels and high salinities due to evapoconcentration that
      were simulated for dry future climates in the absence of sea-level rise. These
      findings strongly suggest that future ecological degradation in the Coorong is
      not a foregone conclusion, and that management decisions regarding water
      allocations upstream will determine the ecological future of this coastal lagoon.

PMID- 23967571
TI  - Ecohydrological and socioeconomic integration for the operational management of
      environmental flows.
AB  - Investment in and operation of flow control infrastructure such as dams, weirs,
      and regulators can help increase both the health of regulated river ecosystems
      and the social values derived from them. This requires high-quality and high
      resolution spatiotemporal ecohydrological and socioeconomic information. We
      developed such an information base for integrated environmental flow management
      in the River Murray in South Australia (SA). A hydrological model was used to
      identify spatiotemporal inundation dynamics. River ecosystems were classified and
      mapped as ecohydrological units. Ecological response models were developed to
      link three aspects of environmental flows (flood duration, timing, and inter
      flood period) to the health responses of 16 ecological components at various life
      stages. Potential infrastructure investments (flow control regulators and
      irrigation pump relocation) were located by interpreting LiDAR elevation data,
      digital orthophotography, and wetland mapping information; and infrastructure
      costs were quantified using engineering cost models. Social values were
      quantified at a coarse scale as total economic value based on a national survey
      of willingness-to-pay for four key ecological assets; and at a local scale using
      mapped ecosystem service values. This information was integrated using a
      constrained, nonlinear, mixed-integer, compromise programming optimization model
      and solved using a stochastic Tabu search algorithm. We tested the model
      uncertainty and sensitivity using 390 Monte Carlo model runs at varying weights
      of ecological health vs. social values. Integrating ecohydrological and
      socioeconomic information identified environmental flow management regimes that
      efficiently achieved both ecological and social objectives. Using an ecologically
      weighted efficient and socially weighted efficient scenario, we illustrated model
      outputs including a suite of cost-effective infrastructure investments and an
      operational plan for new and existing flow control structures including dam
      releases, weir height manipulation, and regulator operation on a monthly time
      step. Both the investments and management regimes differed substantially between
      the two scenarios, suggesting that the choice of weightings on ecological and
      social objectives is important. This demonstrates the benefit of integrating high
      quality and high-resolution spatiotemporal ecohydrological and socioeconomic
      information for guiding the investment in and operational management of
      environmental flows.

PMID- 23967572
TI  - The impact of nitrogen source and crop rotation on nitrogen mass balances in the
      Mississippi River Basin.
AB  - Nitrogen (N) leaching to surface waters from grain farms in the Mississippi River
      Basin (MRB), USA, is the primary cause of hypoxia in the Gulf of Mexico. Regional
      scale N mass balances indicate that a small, intensively cropped area of the
      upper MRB contributes disproportionately to nitrate loading. These aggregate
      balances miss small-scale variability, especially that caused by differences in
      farm management. We constructed N mass balances for a gradient of farm types,
      from corn-soybean monocultures to diversified grain farms that rely on biological
      N fixation (BNF) as a primary N source, to compare the relative efficiency of
      diverse farming systems in the MRB. Five-year N balances were calculated for a
      most and least productive field on each farm using data collected from interviews
      with 95 grain farmers in Iowa, Ohio, Minnesota, and Wisconsin; from legume
      biomass and corn grain samples collected from a subset of farms; and published
      values from the literature. Nitrogen balances ranged from high average annual
      surpluses (149 kg N x ha(-1) x yr(-1)) to large deficits (80 kg N x ha(-1) x yr(
      1)), and differed based on N source and crop rotation. Fields with > 50% of total
      N additions from legume N sources and fields with complex crop rotations that
      included both annual and perennial species were approximately in balance (3.7 kg
      N x ha(-1) x yr(-1) and 5.7 kg N x ha(-1) x yr(-1), respectively) compared to
      fertilizer-based practices in corn-soybean rotations with average annual
      surpluses near 35 kg N x ha(-1) x yr(-1). Surplus N was also inversely related to
      the proportion of total N inputs from BNF for medium (80-160 kg N x ha(-1) x yr(
      1)) to high (> 160 kg N x ha(-1) x yr(-1)) N rates. Diversified farmers were more
      likely to adjust their management practices in response to environmental
      variability compared to fertilizer-based farmers. Taken together, results from
      this study suggest that significantly reducing surplus N in agroecosystems will
      require reducing N inputs and increasing C availability to support the internal
      biological mechanisms for storing N in farm fields.

PMID- 23967573
TI  - Habitat loss drives threshold response of benthic invertebrate communities to
      deposited sediment in agricultural streams.
AB  - Agricultural land uses can impact stream ecosystems by reducing suitable habitat,
      altering flows, and increasing inputs of diffuse pollutants including fine
      inorganic sediment (< 2 mm). These changes have been linked to altered community
      composition and declines in biodiversity. Determining the mechanisms driving
      stream biotic responses, particularly threshold impacts, has, however, proved
      elusive. To investigate a sediment threshold response by benthic invertebrates,
      an intensive survey of 30 agricultural streams was conducted along gradients of
      deposited sediment and dissolved nutrients. Partial redundancy analysis showed
      that invertebrate community composition changed significantly along the gradient
      of deposited fine sediment, whereas the effect of dissolved nitrate was weak.
      Pollution-sensitive invertebrates (%EPT, Ephemeroptera, Plecoptera, Trichoptera)
      demonstrated a strong nonlinear response to sediment, and change-point analysis
      indicated marked declines beyond a threshold of -20% fine sediment covering the
      streambed. Structural equation modeling indicated that decreased habitat
      availability (i.e., coarse substrate and associated interstices) was the key
      driver affecting pollution-sensitive invertebrates, with degraded riparian
      condition controlling resources through direct (e.g., inputs) and indirect (e.g.,
      flow-mediated) effects on deposited sediment. The identification of specific
      effects thresholds and the underlying mechanisms (e.g., loss of habitat) driving
      these changes will assist managers in setting sediment criteria and standards to
      better guide stream monitoring and rehabilitation.

PMID- 23967574
TI  - Food web structure in oil sands reclaimed wetlands.
AB  - Boreal wetlands play an important role in global carbon balance. However, their
      ecosystem function is threatened by direct anthropogenic disturbance and climate
      change. Oil sands surface mining in the boreal regions of Western Canada denudes
      tracts of land of organic materials, leaves large areas in need of reclamation,
      and generates considerable quantities of extraction process-affected materials.
      Knowledge and validation of reclamation techniques that lead to self-sustaining
      wetlands has lagged behind development of protocols for reclaiming terrestrial
      systems. It is important to know whether wetlands reclaimed with oil sands
      process materials can be restored to levels equivalent to their original
      ecosystem function. We approached this question by assessing carbon flows and
      food web structure in naturally formed and oil sands-affected wetlands
      constructed in 1970-2004 in the postmining landscape. We evaluated whether a
      prescribed reclamation strategy, involving organic matter amendment, accelerated
      reclaimed wetland development, leading to wetlands that were more similar to
      their natural marsh counterparts than wetlands that were not supplemented with
      organic matter. We measured compartment standing stocks for bacterioplankton,
      microbial biofilm, macrophytes, detritus, and zoobenthos; concentrations of
      dissolved organic carbon and residual naphthenic acids; and microbial production,
      gas fluxes, and aquatic-terrestrial exports (i.e., aquatic insect emergence). The
      total biomass of several biotic compartments differed significantly between oil
      sands and reference wetlands. Submerged macrophyte biomass, macroinvertebrate
      trophic diversity, and predator biomass and richness were lower in oil sands
      affected wetlands than in reference wetlands. There was insufficient evidence to
      conclude that wetland age and wetland amendment with peat-mineral mix mitigate
      effects of oil sands waste materials on the fully aquatic biota. Although high
      variability was observed within most compartments, our data show that 20-year-old
      wetlands containing oil sands material have not yet reached the same level of
      function as their reference counterparts.

PMID- 23967575
TI  - Time-lagged variation in pond density and primary productivity affects duck nest
      survival in the Prairie Pothole Region.
AB  - The Prairie Pothole Region (PPR) is the primary breeding region for most species
      of North American dabbling ducks (Anas spp.). Conservation of these species is
      guided in part by knowledge of relationships between nest survival probability
      and habitat features. Positive relationships between duck nest survival and
      amount and configuration of herbaceous perennial vegetation have been observed in
      previous studies, but these 2- to 4-year studies might not have adequately
      characterized the temporal effect of wet-dry episodes on nest survival. Over an
      eight-year period, we studied nest survival of five species of ducks in the PPR
      relative to spatial and temporal variation in pond density, primary productivity,
      and hydrologic status of wetlands, soil, and vegetation on 52 study sites
      selected to span a gradient of spatial variation in proportion of herbaceous
      perennial vegetation and in number of wetland basins. We observed the fate of 12
      754 nests. Consistent with past studies, 90% of nests that failed to hatch were
      destroyed by predators. Nest survival probability was positively related to
      current-year pond density and primary productivity, negatively related to pond
      density and primary productivity during the previous two years, and positively
      related to the number of wetland basins on the study site. Predicted
      relationships between nest survival and proportion or configuration of herbaceous
      perennial vegetation in the surrounding landscape were not supported. For mallard
      (Anas platyrhynchos), median estimated nest survival probability ranged from 0.02
      (SE = 0.01) to 0.22 (SE = 0.02). Estimated nest survival was greatest on sites
      with numerous wetland basins that had transitioned from dry, unproductive
      conditions to wet, productive conditions in the previous 1-2 years. Our results
      were consistent with time-lagged responses of food webs to resource pulses in a
      broad array of ecosystems. Our study highlighted the importance of wetland basins
      and wet-dry episodes to duck nest survival in the PPR. Current habitat
      conservation efforts focus on landscapes with numerous wetland basins and a high
      proportion of herbaceous perennial vegetation. Our results suggest that future
      conservation efforts should focus on preserving high-density wetland complexes
      across as large a geographic extent as possible even in cropland-dominated
      landscapes.

PMID- 23967576
TI  - Predicted responses of invasive mammal communities to climate-related changes in
      mast frequency in forest ecosystems.
AB  - Predicting the dynamics and impacts of multiple invasive species can be complex
      because ecological relationships, which occur among several trophic levels, are
      often incompletely understood. Further, the complexity of these trophic
      relationships exacerbates our inability to predict climate change effects on
      invaded ecosystems. We explore the hypothesis that interactions between two
      global change drivers, invasive vertebrates and climate change, will potentially
      make matters worse for native biodiversity. In New Zealand beech (Nothofagus
      spp.) forests, a highly irruptive invasive mammal community is driven by multi
      annual resource pulses of beech seed (masting). Because mast frequency is
      predicted to increase with climate change, we use this as a model system to
      explore the extent to which such effects may influence invasive vertebrate
      communities, and the implications of such interactions for native biodiversity
      and its management. We build on an established model of trophic interactions in
      the system, combining it with a logistic probability mast function, the
      parameters of which were altered to simulate either contemporary conditions or
      conditions of more or less frequent masting. The model predicts that increased
      mast frequency will lead to populations of a top predator (the stoat) and a
      mesopredator (the ship rat) becoming less irruptive and being maintained at
      appreciably higher average abundances in this forest type. In addition, the
      ability of both current and in-development management approaches to suppress
      invasive mammals is predicted to be compromised. Because invasive mammals are key
      drivers of native fauna extinction in New Zealand, with the additional loss of
      associated functions such as pollination and seed dispersal, these predictions
      imply potentially serious adverse impacts of climate change for the conservation
      of biodiversity and ecosystem function. Our study also highlights the importance
      of long-term monitoring data for assessing and managing future impacts of global
      change drivers.

PMID- 23967577
TI  - Using economic instruments to develop effective management of invasive species:
      insights from a bioeconomic model.
AB  - Economic growth is recognized as an important factor associated with species
      invasions. Consequently, there is increasing need to develop solutions that
      combine economics and ecology to inform invasive species management. We developed
      a model combining economic, ecological, and sociological factors to assess the
      degree to which economic policies can be used to control invasive plants. Because
      invasive plants often spread across numerous properties, we explored whether
      property owners should manage invaders cooperatively as a group by incorporating
      the negative effects of invader spread in management decisions (collective
      management) or independently, whereby the negative effects of invasive plant
      spread are ignored (independent management). Our modeling approach used a dynamic
      optimization framework, and we applied the model to invader spread using Linaria
      vulgaris. Model simulations allowed us to determine the optimal management
      strategy based on net benefits for a range of invader densities. We found that
      optimal management strategies varied as a function of initial plant densities. At
      low densities, net benefits were high for both collective and independent
      management to eradicate the invader, suggesting the importance of early detection
      and eradication. At moderate densities, collective management led to faster and
      more frequent invader eradication compared to independent management. When we
      used a financial penalty to ensure that independent properties were managed
      collectively, we found that the penalty would be most feasible when levied on a
      property's perimeter boundary to control spread among properties. At the highest
      densities, the optimal management strategy was "do nothing" because the economic
      costs of removal were too high relative to the benefits of removal. Spatial
      variation in L. vulgaris densities resulted in different optimal management
      strategies for neighboring properties, making a formal economic policy to
      encourage invasive species removal critical. To accomplish the management and
      enforcement of these economic policies, we discuss modification of existing
      agencies and infrastructure. Finally, a sensitivity analysis revealed that
      lowering the economic cost of invader removal would strongly increase the
      probability of invader eradication. Taken together, our results provide
      quantitative insight into management decisions and economic policy instruments
      that can encourage invasive species removal across a social landscape.

PMID- 23967578
TI  - Forest lepidopteran communities are more resilient to shelterwood harvests
      compared to more intensive logging regimes.
AB  - A common measure of ecosystem resilience is the time course to recovery for a
      system that has been previously disturbed. The goal of this study was to assess
      whether forest lepidopteran communities displayed three different forms of
      resilience following experimental timber harvest. Specifically, I examined
      whether moth species assemblages returned to pre-logging composition
      (compositional resilience), species richness (structural resilience), and guild
      diversity (functional resilience) after forest management. Lepidoptera were
      sampled from 16 forest stands managed with one of four harvest treatments: no
      logging, clear-cutting, shelterwood harvests, and group selection harvests. Moths
      were sampled from all forest stands one year prior to harvest in 2007 and
      immediately postharvest in 2009-2011. Moth community composition only appeared to
      be resilient to timber harvest in stands managed with shelterwood methods (15%
      biomass removed) or in the unlogged stands within managed concession units. Both
      total species richness and species richness of Quercus-feeding moths also
      appeared to recover to a near original condition three years post-shelterwood
      logging. In contrast, moth assemblages in clear-cut stands and group selection
      stands (80% biomass removed) remained impoverished. Tests of functional
      resilience suggested that richness of species known to be pollinators was largely
      unaffected by timber management, and the number of moth species known to feed on
      herbaceous vegetation doubled in stands logged using group selection methods.
      Dietary specialists were disproportionately abundant in the unlogged stands
      postharvest, suggesting that species with more narrow dietary niches have the
      lowest resilience to timber management. These results suggest that most methods
      of forest management have short-term negative impacts on woody-plant-feeding
      Lepidoptera, but that the effects are limited to a few years when the harvest
      method involves shelterwood cuts. Herbaceous-feeding Lepidoptera appear to
      quickly colonize stands managed with group selection or clear-cutting, so loss of
      species richness in stands managed with either of these treatments may be less
      than predicted based on level of timber being removed. Recovery of moth
      assemblages in more highly disturbed stands will require longer time periods and
      techniques such as group selection harvests, where upwards of 80% of the standing
      bole is removed, may not be consistent with conservation goals.

PMID- 23967580
TI  - Early recruitment dynamics in tropical restoration.
AB  - Unassisted secondary succession in abandoned tropical pastures often results in
      species-poor forests of pioneer trees that persist for decades. We characterize
      recruitment rates of woody vegetation in planting treatments during the first 60
      months of experimental restoration on thin, eroded soils at Los Tuxtlas, southern
      Mexico. We test the hypothesis that recruitment of later-successional trees is
      greater in fenced plots planted with native trees than in fenced controls that
      simulate natural succession, and further that recruitment of such species would
      be greater in plots planted with animal-dispersed trees than in those planted
      with wind-dispersed trees. Results indicated much greater recruitment of later
      successional animal-dispersed trees in planted plots as compared with controls.
      Three censuses per year recorded 960 recruited individuals of 44 species of trees
      and shrubs from 20-60 months after cattle exclusion. Ninety-six percent of
      recruits were not of planted species. Repeated-measures analyses of variance
      indicated that recruited communities included more species of pioneers than of
      later-successional trees and shrubs, with more individuals and species dispersed
      by animals than by wind. Recruitment of pioneers did not differ between control
      and planted plots. Later-successional recruits dispersed by animals accumulated >
      10 times faster in planted than control plots, with apparent acceleration after
      planted Cecropia obtusifolia and Ficus yoponensis first produced fleshy fruits 48
      months after cattle exclusion. Sparse later-successional wind-dispersed recruits
      did not differ by treatment. Our preliminary results over the first five years
      after cattle exclusion indicate that planted stands clearly accelerate succession
      through accumulation of later-successional trees and shrubs dispersed by animals.

PMID- 23967579
TI  - Mapping the margin: comparing marginal values of tropical forest remnants for
      pollination services.
AB  - Natural ecosystems benefit human communities by providing ecosystem services such
      as water purification and crop pollination. Mapping ecosystem service values has
      become popular, but most are static snapshots of average value. Estimating
      instead the economic impacts of specific ecosystem changes can better inform
      typical resource decisions. Here we develop an approach to mapping marginal
      values, those resulting from the next unit of ecosystem change, across
      landscapes. We demonstrate the approach with a recent model of crop pollination
      services in Costa Rica, simulating deforestation events to predict resulting
      marginal changes in pollination services to coffee farms. We find that marginal
      losses from deforestation vary from zero to US$700/ha across the landscape.
      Financial risks for farmers from these losses and marginal benefits of forest
      restoration show similar spatial variation. Marginal values are concentrated in
      relatively few forest parcels not identified using average value. These parcels
      lack substitutes: nearby forest parcels that can supply services in the event of
      loss. Indeed, the marginal value of forest parcels declines exponentially with
      the density of surrounding forest cover. The approach we develop is applicable to
      any ecosystem service. Combined with information on costs, it can help target
      conservation or restoration efforts to optimize benefits to people and
      biodiversity.

PMID- 23967581
TI  - Plant diversity affects behavior of generalist root herbivores, reduces crop
      damage, and enhances crop yield.
AB  - Soil-dwelling pests inflict considerable economic damage in agriculture but are
      hard to control. A promising strategy to reduce pest pressure on crops is to
      increase the plant diversity in agroecosystems. This approach, however, demands a
      sound understanding of species' interactions, which is widely lacking for
      subterranean herbivore-plant systems. Here, we examine the effects of plant
      diversification on wireworms, the soil-dwelling larvae of click beetles that
      threaten crops worldwide. We conducted a field experiment employing plant
      diversification by adding either wheat or a mix of six associated plants
      (grasses, legumes, and forbs) between rows of maize to protect it from Agriotes
      wireworms. Wireworm feeding behavior, dispersal between crop and associated
      plants, as well as maize damage and yield were examined. The former was assessed
      combining molecular gut content and stable isotope analysis. The pests were
      strongly attracted by the associated plants in August, when the crop was most
      vulnerable, whereas in September, shortly before harvest, this effect occurred
      only in the plant mix. In maize monoculture, the larvae stayed in the principal
      crop throughout the season. Larval delta13C signatures revealed that maize
      feeding was reduced up to sevenfold in wireworms of the vegetationally
      diversified treatments compared to those of the maize monoculture. These findings
      were confirmed by molecular analysis, which additionally showed a dietary
      preference of wireworms for specific plants in the associated plant mix. Compared
      to the monoculture, maize damage was reduced by 38% and 55% in the wheat and
      plant mix treatment, which translated into a yield increase of 30% and 38%,
      respectively. The present findings demonstrate that increasing the plant
      diversity in agroecosystems provides an effective insurance against soil pests.
      The underlying mechanisms are the diversion of the pest from the principle crop
      and a changed feeding behavior. The deployment of diverse mixes of associated
      plants, tailored to the specific preferences of the soil herbivores, provides a
      promising strategy for managing subterranean pests while maintaining crop yield.

PMID- 23967582
TI  - Increasing participation in incentive programs for biodiversity conservation.
AB  - Engaging private landowners in conservation activities for imperiled species is
      critical to maintaining and enhancing biodiversity. Market-based approaches can
      incentivize conservation behaviors on private lands by shifting the benefit-cost
      ratio of engaging in activities that result in net conservation benefits for
      target species. In the United States and elsewhere, voluntary conservation
      agreements with financial incentives are becoming an increasingly common
      strategy. While the influence of program design and delivery of voluntary
      conservation programs is often overlooked, these aspects are critical to
      achieving the necessary participation to attain landscape-scale outcomes. Using a
      sample of family-forest landowners in the southeast United States, we show how
      preferences for participation in a conservation program to protect an at-risk
      species, the gopher tortoise (Gopherus polyphemus), are related to program
      structure, delivery, and perceived efficacy. Landowners were most sensitive to
      programs that are highly controlling, require permanent conservation easements,
      and put landowners at risk for future regulation. Programs designed with greater
      levels of compensation and that support landowners' autonomy to make land
      management decisions can increase participation and increase landowner acceptance
      of program components that are generally unfavorable, like long-term contracts
      and permanent easements. There is an inherent trade-off between maximizing
      participation and maximizing the conservation benefits when designing a
      conservation incentive program. For conservation programs targeting private lands
      to achieve landscape-level benefits, they must attract a critical level of
      participation that creates a connected mosaic of conservation benefits. Yet,
      programs with attributes that strive to maximize conservation benefits within a
      single agreement (and reduce risks of failure) are likely to have lower
      participation, and thus lower landscape benefits. Achieving levels of landowner
      participation in conservation agreement programs that deliver lasting, landscape
      level benefits requires careful attention not only to how the program structure
      influences potential conservation benefits, but also how it influences landowners
      and their potential to participate.

PMID- 23967583
TI  - A seasonal nitrogen deposition budget for Rocky Mountain National Park.
AB  - Nitrogen deposition is a concern in many protected ecosystems around the world,
      yet few studies have quantified a complete reactive nitrogen deposition budget
      including all dry and wet, inorganic and organic compounds. Critical loads that
      identify the level at which nitrogen deposition negatively affects an ecosystem
      are often defined using incomplete reactive nitrogen budgets. Frequently only wet
      deposition of ammonium and nitrate are considered, despite the importance of
      other nitrogen deposition pathways. Recently, dry deposition pathways including
      particulate ammonium and nitrate and gas phase nitric acid have been added to
      nitrogen deposition budgets. However, other nitrogen deposition pathways,
      including dry deposition of ammonia and wet deposition of organic nitrogen, still
      are rarely included. In this study, a more complete seasonal nitrogen deposition
      budget was constructed based on observations during a year-long study period from
      November 2008 to November 2009 at a location on the east side of Rocky Mountain
      National Park (RMNP), Colorado, USA. Measurements included wet deposition of
      ammonium, nitrate, and organic nitrogen, PM2.5 (particulate matter with an
      aerodynamic diameter less than 2.5 microm, nitrate, and ammonium) concentrations
      of ammonium, nitrate, and organic nitrogen, and atmospheric gas phase
      concentrations of ammonia, nitric acid, and NO2. Dry deposition fluxes were
      determined from measured ambient concentrations and modeled deposition
      velocities. Total reactive nitrogen deposition by all included pathways was found
      to be 3.65 kg N x ha(-1) yr(-1). Monthly deposition fluxes ranged from 0.06 to
      0.54 kg N x ha(-1)yr(-1), with peak deposition in the month of July and the least
      deposition in December. Wet deposition of ammonium and nitrate were the two
      largest deposition pathways, together contributing 1.97 kg N x ha(-1)yr(-1) or
      54% of the total nitrogen deposition budget for this region. The next two largest
      deposition pathways were wet deposition of organic nitrogen and dry deposition of
      ammonia; combined they contributed 1.37 kg N x ha(-1)yr(-1) or 37% of the total
      nitrogen deposition budget. To better understand the nitrogen cycle and key
      interactions between the atmosphere and biosphere we need to include as many
      sources and types of nitrogen as possible and understand their variability
      throughout the year. Here we examine the components of the nitrogen deposition
      budget to better understand the factors that influence the different deposition
      pathways and their seasonal variations.

PMID- 23967584
TI  - Harvesting tree biomass at the stand level to assess the accuracy of field and
      airborne biomass estimation in savannas.
AB  - Tree biomass is an integrated measure of net growth and is critical for
      understanding, monitoring, and modeling ecosystem functions. Despite the
      importance of accurately measuring tree biomass, several fundamental barriers
      preclude direct measurement at large spatial scales, including the facts that
      trees must be felled to be weighed and that even modestly sized trees are
      challenging to maneuver once felled. Allometric methods allow for estimation of
      tree mass using structural characteristics, such as trunk diameter. Savanna trees
      present additional challenges, including limited available allometry and a
      prevalence of multiple stems per individual. Here we collected airborne lidar
      data over a semiarid savanna adjacent to the Kruger National Park, South Africa,
      and then harvested and weighed woody plant biomass at the plot scale to provide a
      standard against which field and airborne estimation methods could be compared.
      For an existing airborne lidar method, we found that half of the total error was
      due to averaging canopy height at the plot scale. This error was eliminated by
      instead measuring maximum height and crown area of individual trees from lidar
      data using an object-based method to identify individual tree crowns and estimate
      their biomass. The best object-based model approached the accuracy of field
      allometry at both the tree and plot levels, and it more than doubled the accuracy
      compared to existing airborne methods (17% vs. 44% deviation from harvested
      biomass). Allometric error accounted for less than one-third of the total
      residual error in airborne biomass estimates at the plot scale when using
      allometry with low bias. Airborne methods also gave more accurate predictions at
      the plot level than did field methods based on diameter-only allometry. These
      results provide a novel comparison of field and airborne biomass estimates using
      harvested plots and advance the role of lidar remote sensing in savanna
      ecosystems.

PMID- 23967585
TI  - Earthworm effects on the incorporation of litter C and N into soil organic matter
      in a sugar maple forest.
AB  - To examine the mechanisms of earthworm effects on forest soil C and N, we double
      labeled leaf litter with 13C and 15N, applied it to sugar maple forest plots with
      and without earthworms, and traced isotopes into soil pools. The experimental
      design included forest plots with different earthworm community composition
      (dominated by Lumbricus terrestris or L. rubellus). Soil carbon pools were 37%
      lower in earthworm-invaded plots largely because of the elimination of the forest
      floor horizons, and mineral soil C:N was lower in earthworm plots despite the
      mixing of high C:N organic matter into soil by earthworms. Litter disappearance
      over the first winter-spring was highest in the L. terrestris (T) plots, but
      during the warm season, rapid loss of litter was observed in both L. rubellus (R)
      and T plots. After two years, 22.0% +/- 5.4% of 13C released from litter was
      recovered in soil with no significant differences among plots. Total recovery of
      added 13C (decaying litter plus soil) was much higher in no-worm (NW) plots (61
      68%) than in R and T plots (20-29%) as much of the litter remained in the former
      whereas it had disappeared in the latter. Much higher percentage recovery of 15N
      than 13C was observed, with significantly lower values for T than R and NW plots.
      Higher overwinter earthworm activity in T plots contributed to lower soil N
      recovery. In earthworm-invaded plots isotope enrichment was highest in
      macroaggregates and microaggregates whereas in NW plots silt plus clay fractions
      were most enriched. The net effect of litter mixing and priming of recalcitrant
      soil organic matter (SOM), stabilization of SOM in soil aggregates, and
      alteration of the soil microbial community by earthworm activity results in loss
      of SOM and lowering of the C:N ratio. We suggest that earthworm stoichiometry
      plays a fundamental role in regulating C and N dynamics of forest SOM.

PMID- 23967586
TI  - Sustained carbon uptake and storage following moderate disturbance in a Great
      Lakes forest.
AB  - Carbon (C) uptake rates in many forests are sustained, or decline only briefly,
      following disturbances that partially defoliate the canopy. The mechanisms
      supporting such functional resistance to moderate forest disturbance are largely
      unknown. We used a large-scale experiment, in which > 6700 Populus (aspen) and
      Betula (birch) trees were stem-girdled within a 39-ha area, to identify
      mechanisms sustaining C uptake through partial canopy defoliation. The Forest
      Accelerated Succession Experiment in northern Michigan, USA, employs a suite of C
      cycling measurements within paired treatment and control meteorological flux
      tower footprints. We found that enhancement of canopy light-use efficiency and
      maintenance of light absorption maintained net ecosystem production (NEP) and
      aboveground wood net primary production (NPP) when leaf-area index (LAI) of the
      treatment forest temporarily declined by nearly half its maximum value. In the
      year following peak defoliation, redistribution of nitrogen (N) in the treatment
      forest from senescent early successional aspen and birch to non-girdled later
      successional species facilitated the recovery of total LAI to pre-disturbance
      levels. Sustained canopy physiological competency following disturbance coincided
      with a downward shift in maximum canopy height, indicating that compensatory
      photosynthetic C uptake by undisturbed, later successional subdominant and
      subcanopy vegetation supported C-uptake resistance to disturbance. These findings
      have implications for ecosystem management and modeling, demonstrating that
      forests may tolerate considerable leaf-area losses without diminishing rates of C
      uptake. We conclude that the resistance of C uptake to moderate disturbance
      depends not only on replacement of lost leaf area, but also on rapid compensatory
      photosynthetic C uptake during defoliation by emerging later successional
      species.

PMID- 23967587
TI  - How taxonomic diversity, community structure, and sample size determine the
      reliability of higher taxon surrogates.
AB  - Ecologists and paleontologists often rely on higher taxon surrogates instead of
      complete inventories of biological diversity. Despite their intrinsic appeal, the
      performance of these surrogates has been markedly inconsistent across empirical
      studies, to the extent that there is no consensus on appropriate taxonomic
      resolution (i.e., whether genus- or family-level categories are more appropriate)
      or their overall usefulness. A framework linking the reliability of higher taxon
      surrogates to biogeographic setting would allow for the interpretation of
      previously published work and provide some needed guidance regarding the actual
      application of these surrogates in biodiversity assessments, conservation
      planning, and the interpretation of the fossil record. We developed a
      mathematical model to show how taxonomic diversity, community structure, and
      sampling effort together affect three measures of higher taxon performance: the
      correlation between species and higher taxon richness, the relative shapes and
      asymptotes of species and higher taxon accumulation curves, and the efficiency of
      higher taxa in a complementarity-based reserve-selection algorithm. In our model,
      higher taxon surrogates performed well in communities in which a few common
      species were most abundant, and less well in communities with many equally
      abundant species. Furthermore, higher taxon surrogates performed well when there
      was a small mean and variance in the number of species per higher taxa. We also
      show that empirically measured species-higher-taxon correlations can be partly
      spurious (i.e., a mathematical artifact), except when the species accumulation
      curve has reached an asymptote. This particular result is of considerable
      practical interest given the widespread use of rapid survey methods in
      biodiversity assessment and the application of higher taxon methods to taxa in
      which species accumulation curves rarely reach an asymptote, e.g., insects.

PMID- 23967588
TI  - The relationship between environmental advocacy, values, and science: a survey of
      ecological scientists' attitudes.
AB  - This article reports the results ofa survey of 1215 nonstudent Ecological Society
      of America (ESA) members. The results pertain to three series of questions
      designed to assess ecologists' engagement in various advocacy activities, as well
      as attitudes on the relationship between environmental advocacy, values, and
      science. We also analyzed the effects of age, gender, and employment categories
      on responses. While many findings are reported, we highlight six here. First,
      ecologists in our sample do not report particularly high levels of engagement in
      advocacy activities. Second, ecologists are not an ideologically unified group.
      Indeed, there are cases of significant disagreement among ecologists regarding
      advocacy, values, and science. Third, despite some disagreement, ecologists
      generally believe that values consistent with environmental advocacy are more
      consonant with ecological pursuits than values based on environmental skepticism.
      Fourth, compared to males, female ecologists tend to be more supportive of
      advocacy and less convinced that environmentally oriented values perturb the
      pursuit of science. Fifth, somewhat paradoxically, ecologists in higher age
      brackets indicate higher engagement in advocacy activities as well as a higher
      desire for scientific objectivity. Sixth, compared to ecologists in other
      employment categories, those in government prefer a greater separation between
      science and the influences of environmental advocacy and values.

PMID- 23967592
TI  - [Engraving a great rheumatologic footprint in China].

PMID- 23967597
TI  - [To insist on evidence-based prevention for the progress and challenges of
      cardiovascular disease: a review of the progress and achievements in prevention
      and control of cardiovascular diseases in recent 10 years].

PMID- 23967598
TI  - [The progress in diagnosis and treatment of digestive diseases in the twenty
      first century].

PMID- 23967599
TI  - [The progress in diagnosis and treatment of endocrine metabolic diseases].

PMID- 23967600
TI  - [The progress in diagnosis and treatment of respiratory diseases].

PMID- 23967601
TI  - [The progress in neurology in China in recent 10 years].

PMID- 23967602
TI  - [Spring season forever: the progress in rheumatology in recent 10 years in
      China].

PMID- 23967603
TI  - [A retrospect and prospect of progress in infectious diseases in China in recent
      10 years].

PMID- 23967604
TI  - [The progress of targeted therapy of hematological malignancies in recent 10
      years].

PMID- 23967605
TI  - [The domestic and overseas progress in viral hepatitis in recent 10 years].

PMID- 23967606
TI  - [The progress in kidney diseases in recent 10 years].

PMID- 23967607
TI  - [The progress in critical care medicine in recent 10 years].

PMID- 23967608
TI  - [An analysis of impact factor of Chinese Journal of Internal Medicine from 2008
      to 2010].
AB  - OBJECTIVE: To analyze the articles and citation published in the Chinese Journal
      of Internal Medicine from 2008 to 2010, in order to investigate the influence
      factors of impact factor (IF). METHODS: All articles published in the Chinese
      Journal of Internal Medicine covered by Chinese Medical Citation Index(CMCI) from
      2008 to 2010 were searched and downloaded. Some article related attributions were
      manual added and their influences to IF were analyzed. RESULTS: A total of 1164
      academic papers were published in the journal in 3 years, with 9.95 references
      per paper. The total citation was 1029 times, with 0.93 time per paper and 0.31
      time per page. Among them, 736 articles were not cited, accounting for 63.2%.
      Original articles, pure clinical articles had good citation output. For fund
      supporting, the citation of articles without fund was higher than those with
      fund. The articles on hematology, cardiology and gastroenterology accounted the
      most, while ICU, emergency and nephrology were the least internal medicine
      reported specialties. Although there exists citation difference among different
      subjects, for considering the absolute values, neurology/psychiatry (0.73 time
      per paper), cardiology (0.65 time per paper) and gastroenterology (0. 54 time per
      paper) had better citation output, while hematology, basic research and
      rheumatology had no good performance to IF. CONCLUSION: We should further
      strengthen acquisition and dissemination of excellent articles, reduce the number
      of non-cited paper, expand periodical visibility, and provide a quick and
      convenient way of literature reading.

PMID- 23967609
TI  - [The citation analysis of Chinese Journal of Internal Medicine from 2005 to
      2011].
AB  - OBJECTIVE: To evaluate the academic level of Chinese Journal of Internal Medicine
      by analyzing its citation status by using bibliometrics method. METHODS: The
      distribution of articles published in Chinese Journal of Internal Medicine from
      January, 2005 to December, 2011 indexed by Chinese Science Citation Database
      (CSCD) was analyzed. RESULTS: A total of 2809 articles were published in Chinese
      Journal of Internal Medicine between January,2005 and December, 2011. Among them,
      832(29.62%) articles were cited for totally 1993 times. There were 14 authors
      whose total citation number in 2005-2011 was > or = 10 times. Authors of the
      cited articles came from 25 provinces, autonomous regions and municipalities. The
      regions from where the articles had the highest citation were Beijing (341
      articles), Shanghai (87 articles), Guangdong (64 articles), Jiangsu (45 articles)
      and Zhejiang (43 articles). The medical institutions with the highest citation
      were Peking Union Medical College Hospital of Peking Union Medical College and
      Chinese Academy of Medical Sciences (205 times), Peking University People's
      Hospital (77 times), and Chinese PLA General Hospital (76 times). CONCLUSIONS:
      Quite a few high level academic papers had been published in Chinese Journal of
      Internal Medicine in recent years. Chinese Journal of Internal Medicine plays a
      good role in enhancing academic exchange.

PMID- 23967610
TI  - [A bibliometric investigation to research fronts of major sub-specialties in
      internal medicine].
AB  - OBJECTIVE: To outline the research fronts of ten major sub-specialties in
      internal medicine. METHODS: Based on their impact factor scores and the
      proportion of the journals of 10 subspecialties (endocrinology & metabolism,
      cardiac & cardiovascular systems, hematology, infectious diseases, nephrology,
      gastroenterology & hepatology, respiratory system, rheumatology, critical care
      medicine, clinical neurology) in Journal Citation Report (JCR), and careful
      consulation of expert clinicians, we identified 50 journals. Their bibliographic
      records (including references) published in 2011 were downloaded, and the
      frequency of the references (citations) in each sub-specialty was counted and the
      highly cited records were extracted. We performed a clustering analysis according
      to the co-cited times among any pairs of the highly cited records. To tag each
      cluster of highly cited records, we browsed the titles and abstracts of all
      highly cited records in the same cluster, and concluded the main topics of each
      cluster. Finally, we extracted the current published papers devoted to particular
      cluster by some clustering analysis indicators. The clusters of highly cited
      records were considered as the intelligence base, and the main topics in current
      papers which citing these highly cited papers were considered as research fronts.
      RESULTS: Totally 50 journals on 10 sub-specialties in internal medicine were
      identified. A total of 202 highly cited papers, 38 clusters (knowledge bases) ,
      and 152 corresponding current citing papers presenting the research fronts were
      selected. CONCLUSIONS: We confirm and present research fronts in 10 major sub
      specialties of internal medicine. This study provides a synchronic structure of
      contemporary research activities in internal medicine sub-specialties.

PMID- 23967611
TI  - [The queries and possible answers in clinical practice in prevention of venous
      thromboembolism in medical inpatients].

PMID- 23967612
TI  - [A reappraisal of non-steroidal antiinflammatory drugs in retarding the
      progression of ankylosing spondylitis].

PMID- 23967613
TI  - [The risk factors and prognosis of transplant-associated thrombotic
      microangiopathy following acute graft-versus-host disease].
AB  - OBJECTIVE: To investigate the risk factors and prognosis of transplant-associated
      thrombotic microangiopathy (TA-TMA) following acute graft-versus-host disease
      (aGVHD), and to evaluate the factors that might influence the prognosis of TA
      TMA. METHODS: A nested case-control study was designed. Cases with TA-TMA (n =
      33) and controls (n = 77) matched for age at allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) and length of follow-up were identified from a cohort
      of 356 patients who suffered from aGVHD after allo-HSCT between 2009 and 2011.
      RESULTS: The median time to presentation of TA-TMA was 3.5 (1.2-23.0) months post
      HSCT. The median time from diagnosis and first-line treatment failure of aGVHD to
      TA-TMA diagnosis was 25 (7-257) days and 15 (5-257) days, respectively. aGVHD
      occurring beyond 60 days after allo-HSCT, initial grade III-IV aGVHD, first-line
      treatment failure and receiving tacrolimus as second-line treatment were
      independently associated with the occurrence of TA-TMA, and patients with two or
      more risk factors were at higher risk (OR = 210.0, P = 0.000). Twenty-two (66.7%)
      TA-TMA patients died. Progressive TA-TMA was the significantly adverse factor
      affecting the survival of TA-TMA cases. None of therapies could improve prognosis
      of patients with TA-TMA. CONCLUSION: Many characteristics of aGVHD were
      associated with TA-TMA, which help us to identify the individuals who are at
      higher risk of developing TA-TMA following aGVHD and to select the more
      reasonable GVHD therapeutic strategies.

PMID- 23967614
TI  - [The association of killer cell immunoglobulin like receptor gene polymorphism
      with cytomegalovirus infection after hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To explore the influence of the killer cell immunoglobulin like
      receptor (KIR) gene polymorphism on cytomegalovirus (CMV) infection and
      pathogenesis after hematopoietic stem cell transplantation (HSCT). METHODS: The
      KIR genotype was determined by sequence-specific primer polymerase chain reaction
      (PCR-SSP) in 138 pairs of donors and recipients before HSCT during October, 2005
      and May, 2011. Posttransplant monitoring for CMVpp65 antigen was performed by
      indirect immune histochemically assays since week 2 after transplantation. The
      differences between CMV positive group and negative group, inhibitive and active
      KIR of donors and recipients, and KIR haplotype frequency of donors and
      recipients were analyzed. RESULTS: There were no significant differences in
      frequency of KIR gene and haplotype AA, AB, BB between the donors and recipients.
      The frequencies of 2DS2 and 2DS4 * 003-007 of donors in CMV positive group were
      obviously lower than those in CMV negative group with significant differences (8%
      vs 16% , P = 0.0420; 3% vs 13%, P = 0.0050). There was no significant difference
      in KIR gene between CMV positive group and CMV negative group. The CMV infection
      rates of haplotype AA, BB, AB donors were 64.38%, 36.84% and 50.00%, while CMV
      infection rates of haplotype AA, BB, AB recipients were 53.73%, 46.15% and
      51.72%, respectively. The CMV infection rate was higher in the patients received
      KIR haplotype AA donor than in those received KIR haplotype BB donor (36.84% vs
      64.38%, P = 0.0299). 2DS4 x 003-007 and haplotype BB of donor were found
      associated with CMV infection in multifactor analysis. CONCLUSION: KIR genotypes
      of donors are associated with CMV infection after HSCT.

PMID- 23967615
TI  - Boston makes us proud: Years of practice makes boston EMS perfect.

PMID- 23967616
TI  - Why spinal immobilization protocols need to be updated was long overdue.

PMID- 23967617
TI  - Author Jim Morrissey, MA, EMT-P, responds.

PMID- 23967618
TI  - Speak up. Effective communication is a key tool for EMS managers.

PMID- 23967619
TI  - Futuristic rides. Think outside the box for vehicles that improve safety &
      workflow.

PMID- 23967620
TI  - Angel in the cath lab. Do dead people see us?

PMID- 23967621
TI  - Trouble at the track. NASCAR fan presents withsignificant chest pain & numbness.

PMID- 23967622
TI  - Along came Sandy. How NYC REMSCO helped coordinate the evacuation of 6000-plus
      patients during Superstorm Sandy.

PMID- 23967623
TI  - Move 'em. Teamwork key to successful transport of 130 patients to new San Diego
      area hospital.

PMID- 23967624
TI  - Apneic oxygenation. Why and how to give a non-breathing patient oxygen.

PMID- 23967625
TI  - When the unthinkable happens. Coordination is key for mass violence incidents.

PMID- 23967626
TI  - The fog of EMS. Debriefing sessions can help clear the air.

PMID- 23967627
TI  - Being Super ready. How technology keeps New Orleans alert, in real time.

PMID- 23967628
TI  - Paramedics teach future doctors. UK medical school leads in training of
      prehospital care for future medics.

PMID- 23967629
TI  - EMS: Exiled memory storage.

PMID- 23967630
TI  - [Scraping technique of stuck needle at Anmian point in the treatment of insomnia:
      a randomized controlled trial].
AB  - OBJECTIVE: To compare the efficacy difference in the treatment of insomnia
      between scraping technique of stuck needle and conventional acupuncture at Anmian
      (Extra). METHODS: One hundred and thirty one cases were randomized into an Anmian
      group (68 cases) and a conventional acupuncture group (63 cases). In the Anmian
      group, Anmian (Extra) was selected. After arrival of qi, the stuck needling was
      adopted by rotating the needle gently in single direction, 2-3 rounds till the
      needle body was stuck tightly. Afterwards, the needle tail was touched gently
      with the index finger to fix the needle body and the needle handle was scraped
      gently with the thumbnail from bottom to up. The needle was retained for 30 min.
      In the conventional acupuncture group, Sanyinjiao (SP 6), Shenmen (HT 7) and
      Baihui (GV 20) were selected and stimulated with reducing technique by rotating
      the needles. The needles were retained for 30 min. The treatment was given once
      every day, continuously for 2 weeks in both groups. The score of each factor and
      the total score in Pittsburgh sleep quality index (PSQI) were assessed before and
      after treatment in the two groups. Additionally, the efficacies of two groups
      were evaluated. RESULTS: For the patients in the conventional acupuncture group,
      the sleep quality and time of falling into spleen after treatment were improved
      as compared with those before treatment (all P < 0.01). The improvement of sleep
      time, sleep efficiency, sleep disturbance, hypnotic drug and daytime dysfunction,
      and PSQI total score did not present statistically significant difference as
      compared with those before treatment (all P > 0.05). After treatment, for the
      patients in the Anmian group, the factor score and total score in PSQI were
      apparently improved as compared with those before treatment (P < 0.01, P < 0.05).
      And the improvements of the above items were superior to the conventional
      acupuncture group (P < 0.01, P < 0.05). The total effective rate was 91.2%
      (62/68) in the Anmian group and was 74.6% (47/63) in the conventional acupuncture
      group. The clinical efficacy in the Anmian group was apparently superior to the
      conventional acupuncture group. CONCLUSION: The scraping technique of stuck
      needle at Anmian (Extra) achieves the superior effect on insomnia as compared
      with the conventional acupuncture.

PMID- 23967631
TI  - [Controlled observation of non-blister acupoint sticking and electroacupuncture
      for bronchial asthma].
AB  - OBJECTIVE: To compare the differences of clinical efficacy for bronchial asthma
      between acupoint sticking combined with ginger-separated moxibustion and
      electroacupuncture combined with ginger-separated moxibustion. METHODS: With a
      randomized and controlled method, one hundred cases were divided into an acupoint
      sticking + ginger-separated moxibustion group (group A) and an electroacupuncture
      + ginger-separated moxibustion group (group E), 50 cases in each one. The Dazhui
      (GV 14), Feishu (BL 13), Tiantu (CV 22) and so on were selected in both groups.
      The treatment was given on the 1st day of each dog-day period and each nine-day
      period after the winter solstice separately. The ginger-separated moxibustion was
      applied in the group A, which was followed by plaster sticking that was made with
      Chinese herbs (including white mustard seed, rhizoma corydalis, euphorbia kansui,
      asarum), glycerin and warm ginger juice. The regular acupuncture,
      electroacupuncture and ginger-separated moxibustion were applied in the group E.
      The scores of recovery cough, control asthma, respiratory frequency, stuffiness
      chest, wheezing and markedly and cured effective rate were compared in two groups
      before and after the treatment. RESULTS: The markedly and cured effective rate
      was 72.0% (36/50) in the group A, which was superior to 46.0% (23/50) in the
      group E (P < 0.05). All the symptom scores in two groups were obviously improved
      after the treatment, in which group A was superior to group E (all P < 0.05).
      CONCLUSION: The acupoint sticking and ginger-separated moxibustion could
      obviously improve clinical symptoms in patients with bronchial asthma, and reduce
      skin irritation of medicine to avoid the blister and relive patients' suffer,
      which has superior effect to electroacupuncture combined with ginger-separated
      moxibustion.

PMID- 23967632
TI  - [Post-stroke depression treated with acupuncture and moxibustion: an evaluation
      of therapeutic effect and safety].
AB  - OBJECTIVE: To evaluate the efficacy and safety of acupuncture and moxibustion in
      the treatment of post-stroke depression (PSD) by regulating the liver and
      strengthening the root prescription. METHODS: In light of the random controlled
      trial principle, 123 cases were randomized into an acupuncture-moxibustion group
      (42 cases), a medication group (40 cases) and an acupuncture + medication group
      (41 cases). In the acupuncture-moxibustion group, the therapy of regulating the
      liver and strengthening the root was applied. Acupuncture was given at Hegu (LI
      4), Taichong (LR 3), Baihui (GV 20, Yintang (GV 29), etc. The granule moxibustion
      was applied at Zhongwan (CV 12), Xiawan (CV 10), Guanyuan (CV 4) and Qihai (CV
      6). The treatment was given once a day and stopped in weekend. In the medication
      group, paroxetine hydrochloride tablets were prescribed for oral administration,
      20 mg each day after breakfast. In the acupuncture + medication group, the
      therapies were adopted as the acupuncture-moxibustion group and the medication
      group. In the 2nd and 4th week of treatment, HAMD was used as the primary index
      and Barthel index as the secondary one for the efficacy assessment in the three
      groups respectively. The spleen and stomach syndrome scale of TCM was used for
      the assessment of TCM syndrome efficacy. Treatment emergent symptom scale (TESS)
      was applied for the safety assessment. RESULTS: In the 4th week of treatment, the
      markedly effective rates were 69.0% (29/42), 65.0% (26/40) and 70.7% (29/41) in
      the acupuncture-moxibustion group, the medication group and the acupuncture +
      medication group respectively. The efficacies of anti-depression were similar in
      comparison among groups (P > 0.05). In the 2nd week of treatment, the improvement
      of HAMD score was significant in the acupuncture + medication group as compared
      with that before treatment and in comparison with the medication group (P < 0.05,
      P < 0.01). As for improving Barthel index, reducing the spleen and stomach
      symptom score of TCM and decreasing the score of TESS, the results in the
      acupuncture-moxibustion group and the acupuncture + medication group were
      superior to those in the medication group (P < 0.05, P < 0.01). CONCLUSION: The
      therapy of acupuncture and moxibustion with regulating the liver and
      strengthening the root achieves the definite efficacy of anti-depression and
      presents the quite high safety in treatment.

PMID- 23967633
TI  - [Acupuncture at ganglion pterygoplatinum for 71 cases of chronic simple
      rhinitis].

PMID- 23967634
TI  - [Observation on clinical efficacy of depression treated with the alliance of
      acupuncture and medication].
AB  - OBJECTIVE: To observe the differences in the clinical efficacy on depression in
      comparison among the alliance of acupuncture and Chinese herbal medicine, simple
      herbal medicine and flupentixol and melitracen tablets. METHODS: Two hundred and
      twenty-seven cases were randomized into a Chinese medicine group(75 cases), an
      acupuncture + medication group(78 cases) and a western medicine group(74 cases).
      In the Chinese medicine group, Shugan Jianwei Anshen Decoction was prescribed, in
      which Radix Bupleuri and Radix Paeoniae Alba were the monarch herbs, one dose a
      day. In the acupuncture + medication group, on the basic treatment of Chinese
      medicine, acupuncture was combined every day at Baihui (GV 20), Sishencong (EX-HN
      1), Shenmen (HT 7), Lingdao (HT 4), Daling (PC 7), Laogong (PC 8), Yongquan (KI
      1), etc. In the western medicine group, deanxit was taken orally, 1 tablet after
      getting up in the morning and after lunch respectively. The treatment lasted for
      8 weeks in the three groups. The change of Hamilton depression scale (HAMD) score
      and clinical efficacy were observed before and after treatment. RESULTS: In 8
      weeks of treatment, in the acupuncture + medication group, 19 cases were cured,
      35 cases were markedly effective, 14 cases were effective and 10 cases failed,
      the effective rate was 87.2%; in the western medicine group, 11 cases were cured,
      32 cases were markedly effective, 18 cases were effective and 13 cases failed,
      the effective rate was 82.4%; in the Chinese medicine group, 5 cases were cured,
      14 cases were markedly effective, 35 cases were effective and 21 cases failed,
      the effective rate was 72.0%. HAMD assessment was done in 8 weeks of treatment,
      which was (5.71 +/- 4.32) scores in the acupuncture + medication group, (6.09 +/-
      3.78) scores in the western medicine group and (9.24 +/- 3.49) in the Chinese
      medicine group, the differences were significant in the Chinese medicine group
      compared with the western medicine group and the acupuncture + medication group
      (both P < 0.05). The differences in the scores after treatment were not
      significant statistically between the acupuncture + medication group and the
      western medicine group (both P > 0.05), but the cured and markedly effective rate
      in the acupuncture + medication group was superior to that in the western
      medicine group (P < 0.05). CONCLUSION: The alliance of acupuncture and medication
      achieves the definite efficacy on depression, characterized as less adverse
      reactions and better safety.

PMID- 23967635
TI  - [Cutting, acupoint catgut-embedding and fire-needle therapy for 43 cases of
      hemorrhoid].

PMID- 23967636
TI  - [Influence of acupuncture and moxibustion on defecation in postoperative patients
      of anal fissure: a randomized controlled trial].
AB  - OBJECTIVE: To verify the clinical efficacy of acupuncture and moxibustion on
      defecating and pain symptoms in postoperative patient of anal fissure. METHODS:
      Two hundred cases of postoperation of anal fissure were randomly divided into an
      acupuncture-moxibustion group and a medication group, 100 cases in each one. The
      basic treatment after the surgery was the same in two groups, besides,
      acupuncture was applied at Zhongliao (BL 33) and Xialiao (BL 34) in the morning
      of first 5 days of postoperative 24 h in the acupuncture-moxibustion group, and
      suspended moxibusiton was applied at Changqiang (GV 1) within 5 to 10 min after
      defecation; while two bags of forlax was orally administrated in the morning of
      first 5 days of postoperative 24 h in the medication group. The pain intensity,
      defecation willingness, defecation difficulty and stool texture during
      postoperative defecation were observed. RESULTS: The defecation pain on the first
      two days after the treatment was not statistically significant between two groups
      (both P > 0.05). From the third day of treatment, the improvements of defecation
      pain in acupuncture-moxibustion group were more obvious than those in the
      medication group (all P < 0.05). The patients in the acupuncture-moxibustion
      group had more positive defecation willingness than those in the medication group
      (all P < 0.05). The differences of defecation difficulty and stool properties in
      two groups had no statistical significance (both P > 0.05). CONCLUSION: The
      intervention treatment of acupuncture and moxibustion has clinical significance
      on relieving pain symptoms and improving defecation willingness in postoperative
      patient of anal fissure.

PMID- 23967637
TI  - [Randomized controlled study on the treatment of knee osteoarthritis with
      different acupuncture methods at different stages].
AB  - OBJECTIVE: To explore the efficacy on knee osteoarthritis (KOA) treated with
      different acupuncture methods at different stages. METHODS: One hundred and
      eighty cases of KOA were divided into stagnation stage, fascia cramp stage and
      tendon lesion stage according to the condition of disease, 60 cases in each
      stage. Each stage was randomized into a staging treatment group and an
      electroacupuncture (EA) group, 30 cases in each one. In the staging treatment
      group, acupuncture at the tendon points of meridians and electric thermal
      needling method were adopted for the cases at the stagnation stage; the small
      needle-knife therapy and bleeding method were used for the cases at the fascia
      cramp stage; and the electric thermal therapy with thick silver needles was
      applied for the cases at the tendon lesion stage. In the EA group, EA was applied
      for the cases of all the three stages at Liangqiu (ST 34), Xuehai (SP 10),
      Yanglingquan (GB 34), etc. RESULTS: The total effective rate was 96.1% (87/90) in
      the staging treatment group and was 91.1% (82/90) in the EA group, without
      significant difference in comparison (P > 0.05). The controlled and remarkably
      effective rate (88.9%, 80/90) in the staging treatment group was higher
      apparently than (62.2%, 56/90) in the EA group (P < 0.001). And in the EA group,
      with the disease progression and the further disease stages, the controlled and
      remarkably effective rate was reduced. After treatment, the scores of symptoms
      and signs were decreased in both groups (both P < 0.001), the improvement in the
      staging treatment group was superior to that in the EA group (P < 0.001).
      CONCLUSION: The different acupuncture methods at the three stages improve
      obviously the clinical effect and are highly targeted. The mechanism of the three
      stages on "meridian muscle region pathology" and the treatment based on the
      disease stages can be the effective approach to KOA.

PMID- 23967638
TI  - [Observation on the clinical efficacy of spasmodic torticollis treated with
      matrix needling technique and acupuncture at "Wuxin points" mainly].
AB  - OBJECTIVE: To compare the difference in the efficacy on spasmodic torticollis
      between matrix needling technique combined with puncturing "Wuxin points" and the
      local injection of botox type A. METHODS: Forty-two cases were randomized into an
      acupuncture group and a botox group, 21 cases in each one. In the acupuncture
      group, the matrix needling technique was used and acupuncture was adopted at
      Fengchi (GB 20), "Wuxin points" [Shuigou (GV 26), bilateral Laogong (PC 8) and
      bilateral Yongquan (KI 1)] and local Ashi points. In the botox group, botox type
      A was injected at several spots of local region. The treatment course was 1 month
      in the two groups. The efficacy in each weekend and the results of follow-up
      visit in half a year after treatment were compared between the two groups.
      RESULTS: In the 1st weekend, the markedly effective rate was 42.8% (9/21) and the
      total effective rate was 90.5% (19/21) in the botox group, which were better than
      those of 4.8% (1/21) and 28.6% (6/21) respectively in the acupuncture group (both
      P < 0.01). In the 2nd weekend, the markedly effective rate was 71.4% (15/21) and
      the total effective rate was 95.2% (20/21) in the botox group, which were better
      than those of 19.1% (4/21) and 61.9% (13/21) respectively in the acupuncture
      group (both P < 0.01). In the 3rd weekend, the markedly effective rate was 66.7%
      (14/21) and the total effective rate was 95.2% (20/21) in the botox group, which
      were better than those of 38.1% (8/21) and 71.4% (15/21) respectively in the
      acupuncture group (both P < 0.05). The markedly effective rate and the total
      effective rate were not different significantly between the two groups in the
      treatment of 1 month and the follow-up visit in half a year (all P > 0.05). There
      was no adverse reaction in the acupuncture group. There were 14 cases of adverse
      reactions in the botox group, in which 9 cases of neck muscular weakness and 5
      cases of neck muscular pain. CONCLUSION: The treatment of matrix needling
      technique and combined with acupuncture at "Wuxin points" achieves the
      significant efficacy on spasmodic torticollis. Although the effect is not
      obtained as quickly as the local injection of botox, the efficacy of matrix
      needling technique is similar to that of botox in the treatment of 1 month and
      the follow-up visit in half a year. Moreover, this therapy has no adverse
      reaction.

PMID- 23967639
TI  - [Drug-seperated moxibustion for 62 cases of breast enlargement].

PMID- 23967640
TI  - [On mistakes in contemporary literatures of extra points in China].
AB  - Contemporary literatures which are taken as the base of literature study of extra
      points are insufficient and lack of reliability. The foundation of study is very
      weak. Based on abundant firsthand materials, analyses are made on the major
      problems of confounded names and locations, unclear quotation and source of
      reference in the study of contemporary literatures of extra points. Meanwhile,
      methods and way of thinking for solving the above mentioned problems are
      discussed in this article as well.

PMID- 23967641
TI  - [Application of Tiantu (CV 22) in emergency].
AB  - The operation and application of Tiantu (CV 22) in emergency are discussed in the
      paper. The stimulating methods at Tiantu (CV 22) are acupuncture and pressing
      technique. The correct insertion of needle and proper depth and direction of
      insertion are required during acupuncture. The pressing technique stress the
      pressing strength and pressing time. Acupuncture or pressing technique is
      suitable for the emergent measurement of asthma, asthmatic breathing, coma,
      blockage of phlegm, hiccup, sore throat, etc. It is indicated that Tiantu (CV 22)
      is the key point in the emergency and phlegm resolving. Based on the
      characteristics of the point as promoting qi circulation, reducing the reversed
      qi and resolving phlegm, in light of the proper points combination by different
      syndromes and in terms of the correct and safe stimulating methods, Tiantu (CV
      22) can achieve the immediate therapeutic effects in the emergent situations.

PMID- 23967642
TI  - [Acupuncture at Yinlingquan (SP 9), Taichong (LR 3) mainly plus blood-letting
      therapy for 52 cases of gout].

PMID- 23967643
TI  - [Fu's acupuncture for 20 cases of exacerbation of chronic obstructive pulmonary
      disease].

PMID- 23967644
TI  - [Effects of electroacupuncture at "Jiaji" (EX-B 2) on myocardial apoptosis and
      the expression of Bcl-2 and Bax in rats with ischemia-reperfusion injury].
AB  - OBJECTIVE: To explore the protective mechanism of acupuncture on myocardial
      ischemia-reperfusion injury. METHODS: Fifty Wistar rats were randomly divided
      into a sham-operation group, a model group, a Jiaji group , a Neiguan group and a
      Yanglingquan group, 10 rats in each group. The model of myocardial ischemia
      reperfusion injury was duplicated by ligating the left anterior descending
      coronary artery (LADCA) in the later four groups, and the LADCA was not ligated
      in the sham-operation group. The rats in the treatment groups were treated with
      electroacupuncture at "Jiaji" (EX-B 2), "Neiguan" (PC 6) and "Yanglingquan" (GB
      34) on both sides, respectively, once a day for 7 days. No interventions were
      produced in the sham-operation group and model group. Myocardial apoptosis were
      examined by the TUNEL method. The expressions of Bcl-2 and Bax proteins were
      measured by immunohistochemical method. RESULTS: Apoptosis index(AI) was
      significantly lower in the Jiaji group, Neiguan group and sham-operation group
      compared with model group (P < 0.01). Compared with the sham-operation group, AI
      were significantly increased in other groups (all P < 0.01). There was no
      significant difference in AI between Jiaji and Neiguan group (P > 0.05). Compared
      with the model group, the expression of Bcl-2 was significantly increased and Bax
      protein was significantly decreased in Jiaji group and Neiguan group (both P <
      0.01). The expressions of Bcl-2 and Bax proteins were significantly increased in
      other groups compared with the sham-operation group (all P < 0.01). There was no
      significant difference in the expression of Bcl-2 and Bax proteins between Jiaji
      and Neiguan group (P > 0.05). CONCLUSION: Electroacupuncture at both Jiaji (EX-B
      2) and Neiguan (PC 6) has protective effects on myocardial ischemia-reperfusion
      injury, and the mechanism is closely related to inhibiting myocardial apoptosis
      by adjusting the expression of Bcl-2 and Bax.

PMID- 23967645
TI  - [Effects of electroacupuncture on the expressions of neuroal nitric oxide
      synthase and astrocyte in dentate gyrus of rats with Parkinson's disease].
AB  - OBJECTIVE: To observe the changes in the expression of neuroal nitric oxide
      synthase (nNOS) and glial fibrillary acidic protein (GFAP) in dentate gyrus (DG)
      of rats with Parkinson's disease (PD) and effects of electroacupuncture (EA).
      METHODS: On the 7th day of stereotactic injection with 6-hydroxydopamine into
      right medial forebrain bundle, apomorphine-induced rotation was carried out to
      select the PD rats. The selected 12 rats were randomly divided into a model group
      (n = 6) and an EA group (n = 6). Moreover a normal group was established (n = 6).
      Then, the rats in EA group were treated with EA at "Hegu" (LI 4) and "Taichong"
      (LR 3), once a day for 21 days, and the other groups without any treatment. After
      EA treatment, the expressions of nNOS and GFAP in right DG were examined by
      immunohistochemistry method. RESULTS: The expression of nNOS in the right DG was
      weak in normal group, and the expression of nNOS in model group was significantly
      higher than that in normal group (P < 0.01), while in EA group, it was
      significantly lower than that in model (P < 0.01), with no difference between EA
      group and normal group (P > 0.05). The expression level of GFAP in model group
      was significantly higher than that in normal group (P < 0.01), while there was no
      difference in the number of GFAP positive cells between the above two groups (P >
      0.05), and the number of GFAP positive cells in EA group was significantly
      increased compared with that in model group (P < 0.01), while with no significant
      difference in the expression level of GFAP between EA group and model group (P >
      0.05). CONCLUSION: EA can reverse the increase of nNOS expression and promote the
      activation of astrocyte in DG on the injured side in rats with PD.

PMID- 23967646
TI  - [Eighty-seven cases of vertigo treated by acupuncture and acupoint injection of
      gastrodin].

PMID- 23967647
TI  - [Acupuncture for 30 cases of hyperplasia of breast].

PMID- 23967648
TI  - [Observation on analgesia effect of acupuncture combined with auricular-sticking
      therapy after laparoscopic cholecystectomy].

PMID- 23967649
TI  - [Briefing on the 61st academic conference of Japanese Acupuncture Association].
AB  - The main content of the 61st Academic Conference of Japanese Acupuncture
      Association is introduced and summarized in this article. Different from former
      conferences, it focuses on the academic activity which take patient into the
      major consideration, and on the feasibility study of aerospace acupuncture
      treatment. Meanwhile, study on Japanese technique of shallow insertion with fine
      needle and its results are also introduced. The developing tendency of Japanese
      Acupuncture Association is discussed at the meeting as well.

PMID- 23967650
TI  - [Exploration on the spectrum of disease and acupoints in post-stroke disorder
      treated with acupuncture and moxibustion on the basis of data mining technology].
AB  - OBJECTIVE: Data mining technology is used to analyze the spectrum of disease and
      acupoints in the treatment of post-stroke disorder with acupuncture and
      moxibustion in modern times. METHODS: The literature resources are formulated,
      the name of disease and acupoint are standardized, the spectrum of acupuncture
      for disease that post-stroke disorder belonged to and their genealogical
      classification are collected, the spectrum of acupoints in the treatment of post
      stroke disorder are summarized. RESULTS: Totally, 652 modern clinical research
      papers are collected, including 9 classification systems in ICD-10 and 40
      diseases; 143 nonacupoints are used and the application frequency are 737; 253
      acupoints are used and the application frequency are 5395. According to
      application frequency, the points are divided into often used points(23 points),
      sometimes used points (100) and less used points (130). CONCLUSION: The lack of
      standardization is the common problem found in modern acupuncture literature in
      the treatment of post-stroke disorders and the spectrum of disease is in biased
      distribution. The selected acupoints are distributed in the fourteen meridians
      and acupoints of yang meridian are the first option. The most common used
      meridians are Yangming and Shaoyang.

PMID- 23967651
TI  - [The role of acupuncture and moxibustion in organized medicine of pain].
AB  - The literature on acupuncture-moxibustion and acupuncture-moxibustion combined
      with other therapies for all kinds of pain as well as organized medicine of pain
      in recent ten years are analyzed. It is found out that application of single
      acupuncture-moxibustion has positive effect on most of pain, while acupuncture
      moxibustion combined with other therapies could improve the efficacy in a certain
      extent. The organized medical model of pain, by integration of clinical paths and
      optimization of medical methods, could achieve best effect on pain. With
      acupuncture-moxibustion joining in the organized medical model of pain, the
      analgesia effect could be enhanced, medical cost decreased and patient's life
      quality improved. The suitable disease, clinical path, action function and
      mechanism need further evidence-based research.

PMID- 23967652
TI  - [Renovation of acupuncture teaching based on opposite points].
AB  - The definition and content of opposite points is updated, and renovation of
      acupuncture teaching is explored in this article. Opposite points interconnect
      meridians and acupoints. Location of one point reminds that of the other in
      pairs. When manipulating, point-to-point puncture from two opposite sides or
      penetrating method from one side are both applicable. It has the advantages of
      less point selection and regulating yin and yang. Its application in teaching of
      meridians, acupoints, acupuncture technique and treatment may bring enthusiasm
      into the study as well as improve the level of teaching.

PMID- 23967653
TI  - [Discussion on application of Jiao Xue].

PMID- 23967654
TI  - [Umbilical ring acupoints and its clinical application in Zhuang medicine].
AB  - The theoretical basis, location, belonging of zang-fu, treatment function and
      indications, applying principle and manipulation of Umbilical Ring acupoints in
      Zhuang medicine are explained in this paper. According to Zhuang medicine,
      umbilicus is an epitome of the body and all the zang-fu and organs in the body
      have corresponding epitomes like a fetus in front-standing position. The
      umbilicus is not only a micro-diagnosis system, but also a window for illness
      treatment that could be divided into superficial, middle and deep layer to
      respectively communicate different zang-fu and organs. The umbilical inner ring
      and outer ring are collectively called Umbilical Ring acupoints, they could
      dredge paths, regulate the balance of qi and blood to regulate qi, expel poison,
      tonify deficiency and remove stasis to treat many types of diseases in the whole
      body.

PMID- 23967655
TI  - [Triple acupuncture combined with ultrashort wave therapy for 36 cases of mouse
      hand].

PMID- 23967656
TI  - [Liu Zhang-Jie's thought of acupuncture education].
AB  - Through retrieving of literature relevant to LIU Zhang-jie, his practicing and
      teaching experience in Quanzhou city are investigated, and his modern education
      thoughts are summarized in this article as well. It is found that LIU attached
      great importance on both apprenticeship and classroom teaching; he highlighted
      the theory of meridians and the classic of Treaties on Febrile Diseases;
      recommending selection of less points, and focusing on finger force during
      practice, he prefered to combine acupuncture with materia medica. He was
      practical and realistic, and never hide his mistakes. He also brought along and
      passed his ideas of acupuncture teach to his students. The medical ethic of SUN
      Si-miao was the one he advocated. He also spared no effort to write books and
      teach materials which played important roles in the spread of Chengjiang
      Acupuncture School.

PMID- 23967657
TI  - [Three successful cases treated with moxibustion and embedding needle at
      auricular points].

PMID- 23967658
TI  - [Progress on research of specificity of acupoint effects during "the 11th five
      year"].
AB  - With retrieval in CNKI and MEDLINE data base, the articles in Chinese and English
      that were written by Chinese authors, which were about the specificity of
      acupoint effects during "the Eleventh Five-Year (2006-2010)", are included.
      Researchers have studied about the specificity of acupoint effects by cerebral
      function imaging technique and it turns out that from the perspective of central
      mechanism, there are differences among aupoint stimulatory effect. The curative
      effect of acupoints is significantly better than that of nonacupoints, different
      acupoints have different curative effects, the effect of disease-related
      acupoints is better than that of unrelated acupoints, those above have intitally
      proved the existence of specificity of acupoint effects. However, part of the
      research results need futher summaries, analysis and promotion as well as try to
      avoid low-level repeat in research design.

PMID- 23967659
TI  - [Virulence factors of Helicobacter pylori].

PMID- 23967660
TI  - [A new approach for extermination of gastric cancer from Japan].
AB  - A gastric cancer elimination project that combines H. pylori eradication therapy
      and endoscopic examination is both appropriate and feasible for Japan, where
      excellent methods of diagnosis and endoscopic treatment for early gastric cancer
      are already available. In this country, the baby-boom generation is now passing
      60 years old and reaching the cancer-prone age, so an increase of medical costs
      related to gastric cancer is impending. Application for medical insurance in
      patients with H. pylori related chronic gastritis due to the Basic Plan to
      Promote Cancer Control Programs might be a first step to eliminate gastric cancer
      deaths in Japan.

PMID- 23967661
TI  - [Epidemiology of H. pylori infection and gastric mucosal atrophy].
AB  - Progress in sanitary conditions, especially development of clean water supply for
      these 50 years has been reducing prevalence of Helicobacter pylori infection in
      Japan. The reduction in corporation with a less intake of highly salted foods and
      probably infection at later ages decreases prevalence and/or severity of gastric
      mucosal atrophy. Consequently, incidence of gastric cancer has been decreasing.
      However, it was unveiled that those with H. pylori infection and gastric mucosal
      atrophy have high risk of gastric cancer even after successful eradication of the
      infection, which still remains as a problem.

PMID- 23967662
TI  - [Transmission route of H. pylori].
AB  - The incidence of Helicobacter pylori (H. pylori) infection is rapidly decreased
      in Japan. H. pylori infection is mainly acquired in the first 2 years life and
      the risk of infection declines rapidly after 5 years of age. Person-to-person
      transmission in the family appears to be the predominant and in the population
      with low prevalence, several studies showed the infected mother is likely to be
      the main source of the infection. H. pylori can be detected from vomitus, saliva
      and cathartic stools and the possibility of source of infection. Waterborne
      infection is unlikely in the developed countries.

PMID- 23967663
TI  - [Mechanism of H. pylori-induced gastric inflammation and carcinogenesis].

PMID- 23967664
TI  - [H. pylori genomics].
AB  - Helicobacter pylori, a major stomach pathogen associated with gastritis,
      gastric/duodenal ulcer, gastric cancer and other diseases, shows extreme
      diversity at the genome sequence level. It is now possible to sequence whole
      genomes of Japanese isolates at a reasonable cost. Here I summarize what has been
      learned from analyzing whole H. pylori genomes. Emphasis is placed on features of
      East Asian strains, genome dynamics and epigenetics. I cover both long-term
      evolution with us Homo sapiens and short-term evolution within our bodies. I hope
      this guide will be helpful for decoding and analyzing H. pylori genomes of
      clinical isolates, especially those from Japan and other East Asian countries.

PMID- 23967665
TI  - [Detection of prehistoric human migration by Helicobacter pylori].
AB  - Helicobacter pylori is not only a well known gastroduodenal pathogen but also a
      useful marker for tracing prehistoric footprints of human populations. Because H.
      pylori transmits mainly through vertical infection and has been carried in our
      stomach from generation to generation, its geneology well reflects that of human.
      We investigated genes of H. pylori from a wide variety of ethnicity and predicted
      the journey of ancient people after the departure from the African Continent in
      100 to 50 thousand years ago. Analysis of genotypes of single genes, multi locus
      sequence typing, and also with the aid of next generation sequencer, we
      identified a group of H. pylori strains that diverged remarkably old era in
      Okinawa, Japan.

PMID- 23967666
TI  - [New Helicobacters other than H. pylori].
AB  - Since discovery of Helicobacter pylori, more than 30 species non-H. pylori
      Helicobacter spp. (NHPH) have been reported. Those NHPH were now classified into
      gastric Helicobacter spp. and enterohepatic Helicobacter spp.(EHS). Gastric NHPH
      show tight spiral and long shape in the gastric mucosa, and we can distinguish
      from H. pylori by light microscope. Some gastric NHPH may be zoonosis and cause
      gastritis in human. H. hepaticus and H. cinaedi belongs in EHS were detected in
      human diseases. H. hepaticus may be associated with hepatobiliary diseases in
      humans. Surprisingly, it was reported that H. cinaedi infection was associated
      with atrial arrhythmias and atherosclerosis. Many NHPH will be recognized as
      human pathogen in the future.

PMID- 23967667
TI  - [Current status of diagnosis of H. pylori infection].
AB  - Helicobacter pylori infection can be diagnosed by several methods using serum,
      urine, stool, breath or gastric samples taken at endoscopic examination. Some
      methods such as a stool antigen test (SAT), an urea breath test (UBT) or gastric
      biopsy-based tests such as a rapid urease test (RUT), histology or culture reveal
      active infection. UBT or SAT is recommended for determining the success of
      eradication treatment. While serum and urine antibodies show exposure to H.
      pylori, positive results do not necessarily indicate that the infection is
      ongoing. We need to know the characters of each test and choose appropriate one
      considering clinical conditions.

PMID- 23967668
TI  - [The practical assessment of H. pylori eradication].
AB  - Helicobacter pylori (H. pylori) gastritis has been approved by Ministry of
      Health, Labour and Welfare as an additional indication for H. pylori eradication
      in Japan on Feburary 21, 2013. Diagnostic methods of H. pylori infection have
      been divided into direct (invasive) and indirect (non-invasive). Invasive tests
      requiring endoscopic biopsy include culture, histology and rapid urease test
      (RUT). Non-invasive tests not requiring endoscopic biopsy include measurement of
      H. pylori antibody(serum, urine), urea breath test(UBT) and stool antigen test.
      Assessment of the efficacy of H. pylori eradication therapy should be performed
      at least 4 weeks after the completion of treatment. UBT and monoclonal stool
      antigen test are both recommended for the assessment of H. pylori eradication.
      When the results obtained is doubtful for assessment of H. pylori eradication, it
      is preferable to perform another test or follow-up.

PMID- 23967669
TI  - [Status and problem of first line eradication of H. pylori infection].
AB  - This year eradication of H. pylori was applied for not only peptic ulcer but also
      chronic gastritis on National insurance system. However recently decrease in
      first line eradication rate of H. pylori using PPI/AC regimen. Certainly
      eradication rate after 2000 decreased in intention to treat (ITT) and per
      protocol(PP) compared to that before 2000. This tendency was induced by increase
      in CAM-resistant H. pylori. But after 2007 eradication rate decreased only in
      ITT, eradication rate didn't decrease in PP. That tendency was induced by bad
      compliance and evaluation of the eradication.

PMID- 23967670
TI  - [Second-line therapy for Helicobacter pylori].
AB  - Currently, the recommended second-line eradication regimen for Helicobacter
      pylori is a quadruple therapy consisting of PPI, bismuth, tetracycline and
      metronidazole. Recently, levofloxacin-based (PPI, levofloxacin and amoxicillin)
      and moxifloxacin-based (PPI, moxifloxacin and amoxicillin) triple therapy
      represent promising alternative. In Japan, PPI-based triple therapy (PPI,
      amoxicillin and metronidazole) is used for second-line regimen after failure of
      first-line eradication. The rate of second-line eradication is still
      high(approximately 90% (ITT)) and triple therapy with PPI, AMPC, and MNZ may
      still be considered useful for second-line eradication therapy of Helicobacter
      pylori in Japan. High-dose dual therapy with PPI and amoxicillin for 2 weeks may
      be useful treatment strategy after failure of first-line eradication.

PMID- 23967671
TI  - [Present status and future prospects of third line rescue regimens for H. pylori
      infection].
AB  - Recent reports have suggested that the candidates of the third rescue regimens
      for H. pylori infection in Japan are fluoroquinolone-based regimens and the dual
      therapy with high doses of proton pump inhibitor and amoxicillin. Of
      fluoroquinolones, sitafloxacin has the strong anti-H. pylori effect as AMPC has
      and is effective for strains resistant to levofloxacin. Sitafloxacin-based
      regimens have been reported to yield relatively sufficient eradication rates as
      the third line therapy. The dual therapy with high doses of proton pump inhibitor
      and amoxicillin has also been reported to attain the sufficient rescue rates. To
      achieve the high rescue eradication rates, the eradication regimens must be
      designed based on well-understanding of reasons for eradication failure, such as
      the resistance patterns of the bacteria, and the pharmacological characteristics
      of agents used for H. pylori eradication therapy.

PMID- 23967672
TI  - [Helicobacter pylori eradication therapy in children].
AB  - Helicobacter pylori eradication therapy is recommended in the presence of H.
      pylori positive peptic ulcer disease and refractory iron deficiency anemia in
      adolescents among Japanese children. The eradication rate of the first-line
      triple therapy with a PPI+ amoxicillin+clarithromycin is falling to about 70%. A
      triple therapy with a PPI+ amoxicillin+metronidazole is acceptable as the second
      line therapy. According to recent reports, the clarithromycin resistance rate is
      more than 40% in Japanese children. Antibiotics susceptibility testing before
      first-line therapies is taken into account. There is no available data about
      sequential therapy in Japanese children. The 13C-urea breath test and/or stool
      antigen test are recommended for confirmation of eradication at least 4 to 8
      weeks following completion of therapy.

PMID- 23967673
TI  - [Gastric ulcer and duodenal ulcer].
AB  - Peptic ulcer diseases are improved by strong acid suppression therapy. However,
      peptic ulcer diseases are often relapsed after discontinuing of acid suppression
      therapy. After discovery of Helicobacter pylori (H. pylori) in 1984, H. pylori is
      known as the strongest causal agent for peptic ulcer diseases. In November 2000,
      eradication therapy for H. pylori infection was approved under the Japanese
      system of health insurance. H. pylori eradication reduces ulcer recurrence
      dramatically. Recently, peptic ulcer diseases induced by NSAIDs and/or aspirin
      are increasing. In prevention of NSAIDs and/or aspirin induced peptic ulcer
      recurrence, H. pylori eradication plus PPI treatment is recommended. Several
      reports described occurrence of newly-developed gastric cancer after H. pylori
      eradication. Careful follow-up upper gastrointestinal endoscopy is necessary
      after H. pylori eradication.

PMID- 23967674
TI  - [Helicobacter pylori eradication for gastric MALT lymphoma].
AB  - Clinical features and efficacy of Helicobacter pylori (H. pylori) eradication for
      patients with gastric MALT lymphoma are reviewed. Gastric MALT lymphoma comprises
      1-5% of all gastric malignancies, while 40-50% of primary gastric lymphomas. In
      approximately 90% of cases, H. pylori infection plays the causative role in the
      pathogenesis, and H. pylori eradication is nowadays the first-line treatment for
      this disease, which leads to complete disease remission in 60-90% of cases.
      Predictive factors for resistance to eradication therapy include absence of H.
      pylori infection, deep invasion in the gastric wall, t(11:18)/API2-MALT1, and
      etc. Recently a large-scale Japanese multicenter study demonstrated that the long
      term clinical outcome of gastric MALT lymphoma after H. pylori eradication is
      excellent.

PMID- 23967675
TI  - [After endoscopic treatment of early stage gastric cancer].
AB  - Almost all gastric cancers including intestinal type and diffuse type develop
      from background of H. pylori infection of the gastric mucosa. In treatment of
      gastric cancer, the development of endoscopic technique expanded the indication
      of endoscopic treatment for early gastric cancer. Residual cancers due to
      incomplete resection occur within two years after endoscopic treatment. However,
      metachronous cancers continue to occur for long-term after endoscopic treatment
      of primary cancer. Multi-center, randomized controlled trial in Japan showed that
      H. pylori eradication significantly reduced the incidence of metachronous cancer
      after endoscopic resection. Severe atrophy is high risk factor on metachronous
      gastric cancer after successful eradication. Because H. pylori eradication after
      endoscopic treatment of early gastric cancer have been covered under public
      health insurance, positive eradication therapy for H. pylori infection is
      expected to reduce metachronous cancer.

PMID- 23967676
TI  - [Idiopathic thrombocytopenic purpura].
AB  - In many extragastric manifestations with Helicobacter pylori (HP) infection, the
      most convincing evidences were observed in idiopathic thrombocytopenic purpura
      (ITP). The prevalence of HP infection in ITP was not different to general
      population. The high association of HP infection in ITP was reported in Italy and
      Japan but low in USA and UK. After eradication therapy, platelet counts response
      was found in over 50% of ITP cases in Japan and Italy, and about 40% in other
      countries. The platelet counts response following eradication was maintain for
      long time with drug free and the relapse case was rare. The platelet elevation
      reaction by eradication was not influenced by previous treatment, sex and age,
      but the disease duration as ITP and the platelet count before eradication were
      controversial factors. The main side effects of eradication were diarrhea,
      vomiting and skin rash. Based on these evidences, ITP guideline in Japan (2012)
      recommended that eradication therapy was the first choice treatment for HP
      positive ITP cases.

PMID- 23967677
TI  - [The effect of Helicobacter pylori eradication on chronic gastritis].
AB  - Helicobacter pylori (H. pylori) is a major pathogen of chronic atrophic
      gastritis, intestinal metaplasia, and gastric cancer. Atrophic gastritis and
      intestinal metaplasia are recognized as precancerous lesion of gastric cancer.
      Many studies reported that H. pylori eradication had the preventive effect of
      gastric cancer. Moreover many studies mentioned the improvement of gastric
      atrophy and/or intestinal metaplasia. Two meta-analysis indicated the improvement
      of atrophic gastritis but not of intestinal metaplasia. In our study, intestinal
      metaplasia improved at lesser curvature of the corpus six years after
      eradication. H. pylori eradication has benefit for gastric cancer prevention
      provably due to improvement of the precancerous lesion such as atrophic gastritis
      and intestinal metaplasia. Especially, H. pylori eradication before the
      appearance of atrophy and intestinal metaplasia has been considered to be
      effective in inhibiting the development of gastric cancer. Therefore, improvement
      or elimination of chronic gastritis with H. pylori eradication might have
      possibility of gastric cancer inhibition.

PMID- 23967678
TI  - [Gastric hyperplastic polyps and H. pylori infection, their relationship and
      effects of eradication therapy].
AB  - Gastric hyperplastic polyp is frequently found in the stomach. The polyp almost
      never occurs in normal gastric mucosa and is most commonly associated with
      chronic gastritis induced by H. pylori infection. Most gastric hyperplastic
      polyps disappear after eradication of H. pylori. Eradication therapy is safe, non
      invasive, and reduces medical cost in comparison with polypectomy. It is now
      expected that H. pylori infection rate may decrease in the future, and H. pylori
      eradication treatment in Japan may become more common. Therefore, cases of
      gastric hyperplastic polyp and gastric cancer may decrease.

PMID- 23967679
TI  - [Relationship between Helicobacter pylori status and the development of reflux
      esophagitis or Barrett's esophagus].
AB  - To date, there are many studies on the association between Helicobacter pylori
      (H. pylori) infection and gastroesophageal reflux disease. Here we reviewed the
      relationship between H. pylori status and the development of reflux esophagitis
      (RE) or Barrett's esophagus (BE). According to many case-controlled studies, H.
      pylori infection may play a protective role in the development of RE. However,
      the frequency of RE development does not increase following successful H. pylori
      treatment based on the previous studies including meta-analysis and systematic
      review. Even though RE newly develops after H. pylori eradication, endoscopic
      findings reveal mild such as grade A or B according to the Los Angeles
      Classification System. With regard to BE, there is an inverse significant
      relationship. Since there are few studies indicating that BE increases after
      treatment of H. pylori, the eradication should be recommended for patients with
      H. pylori infection irrespective of the presence of RE or BE even in terms of the
      prevention of gastric cancer.

PMID- 23967680
TI  - [Iron-deficiency anemia].
AB  - Numerous studies have suggested a link between iron-deficiency anemia(IDA) and
      Helicobacter pylori infection. Previously, we found that strains isolated from
      IDA patients showed higher levels of Fe ion uptake and Fe-iron-dependent rapid
      proliferation than those of strains derived from patients without IDA. Recently
      we examined the nucleotide sequences of nap A, fur, and feo B of H. pylori
      strains from 24 IDA patients and those from 25 non-IDA patients. Frequency of
      neutrophil-activating protein A(Nap A), which encoded by nap A, with threonine at
      amino acid residue No. 70 (Thr70-type Nap A) was significantly higher in IDA
      strains than non-IDA strains. Strains with Thr70-type Nap A showed significantly
      higher levels of Fe3+ and Fe2+ uptake than strains with other type, Ser70-type
      Nap A, which is found in standard strains.

PMID- 23967681
TI  - [H. pylori infection and lifestyle related diseases].
AB  - The association between Helicobacter pylori infection and lifestyle related
      diseases was examined in a health survey. The results suggested that 1) infection
      of H. pylori would accelerate the progress of atherosclerosis in elderly men who
      smoke, 2) severe atrophic gastritis caused by H. pylori infection would have a
      significant association with the decrease in serum lipid level, 3) H. pylori
      infection was a decreased risk for tooth loss in healthy men, and 4) H. pylori
      infection was not associated with osteopenia in elderly. Since, clinical
      features, such as proportion of cagA-positive strains and frequency of severe
      atrophic gastritis in elderly are different between Western populations and
      Japanese, further studies based on Japanese patients are required to determine
      the association between H. pylori infection and lifestyle related diseases.

PMID- 23967682
TI  - [Gastric cancer risk classification (ABC classification)].
AB  - Infection with Helicobacter pylori (Hp) is considered a prerequisite for gastric
      carcinogenesis and gastric mucosal atrophy that develops in association with the
      infection is a risk factor for gastric cancer. The gastric cancer risk can be
      diagnosed by the ABC classification consisted of a combination of serum Hp
      antibody and the pepsinogen (PG) method. The ABC classification may contribute to
      gastric cancer screening as well as to primary care of digestive organ practice.
      However, we should remember that we cannot diagnose the gastric cancer by only
      the ABC classification, and an imaging examination is required.

PMID- 23967683
TI  - [European guideline for the management of precancerous conditions in the stomach
      and it's application to Japan].
AB  - Atrophic gastritis, intestinal metaplasia, and Helicobacter pylori (H. pylori)
      infection are commonly recognized as the risk factor of gastric cancer. In Japan
      mass screening by the X-ray examination or endoscopy has been performed for a
      long time in general population or in work place because of the high death rate
      and high incidence of gastric cancer. Periodic endoscopy has been recommended for
      the subjects with atrophic gastritis and/or intestinal metaplasia to detect
      gastric cancer in early stage. On the other hand, there was no guideline to
      manage premalignant conditions such as atrophic gastritis, intestinal metaplasia,
      and dysplasia in foreign countries. Recently the guideline for the management of
      precancerous conditions and lesions in the stomach (MAPS) has been published by
      the combined efforts of the European Society of Gastrointestinal Endoscopy,
      European Helicobacter Study Group, European Society of Pathology, and the
      Sociedade Portuguesa de Endoscopia Digestiva. In this article the main statements
      have been discussed on comparing the understandings as the premalignant
      conditions in Japan.

PMID- 23967684
TI  - [Effect on medical practices after health insurance application for "H. pylori
      gastritis"].
AB  - Eradication therapy for H. pylori infected gastritis became the health insurance
      application in Japan in 2013. It will seem that the conception of "the chronic
      gastritis" greatly changes from now on in Japan. "The chronic gastritis" will be
      classified in H. pylori gastritis and functional dyspepsia in the near future. On
      the other hand, it is expected that the process of the gastric cancer detection
      survey greatly changes too. It seems that the ABC checkup using the blood will be
      carried out in place of Barium examination. A decrease in gastric cancer
      mortality is expected as things mentioned above from now on.

PMID- 23967685
TI  - [Possible role of genetic factors on reduced risk for gastric cancer among
      duodenal ulcer patients].
AB  - Although H. pylori causes both gastric cancer and peptic ulcer, duodenal ulcer
      patients were known to have low risk for gastric cancer. Recently the association
      of PSCA and ABO with duodenal ulcer were identified by GWAS in the Japanese
      population. A T-allele of SNP rs2294008 in the PSCA promoter creates the upstream
      translational initiation codon and affects the protein localization from
      cytoplasm to cell surface. A T-allele of SNP rs2294008 increased gastric cancer
      risk but reduced duodenal ulcer risk. In addition, blood type O was shown to
      increase risk for duodenal ulcer, while blood type A was associated with gastric
      cancer risk in the Caucasian population. Our finding would partially explain low
      risk of gastric cancer among duodenal ulcer patients.

PMID- 23967686
TI  - [The inflammasome].
AB  - Inflammation is a protective response intended to eliminate primary causes of
      tissue injury, leading to tissue repair and adaptation in a focal lesion. It is
      thought that various factors are involved in the histopathological responses to
      tissue injury. One of the inflammatory cytokines, interleukin(IL)-1beta, is
      thought to play an important role in inflammatory responses. The inflammasome is
      a multi-protein complex, required for IL-1beta processing and activation to
      induce inflammation. Over the past decade, evidence has accumulated that the
      inflammasome contributes significantly to the pathogenesis of various diseases.
      In this review, we discuss the function of inflammasome and inflammasome-related
      diseases, that are now expanding beyond inflammation.

PMID- 23967687
TI  - Laureates: awards and honors, SCS Fall Meeting 2012.

PMID- 23967688
TI  - Radicals in stereoselective synthesis and electron transfer reactions.
AB  - This short historical review describes the work of the Giese group on radicals
      and radical ions that has led to the award of the Paracelsus prize in 2012.

PMID- 23967689
TI  - Total synthesis of hematoporphyrin and protoporphyrin; a conceptually new
      approach.
AB  - The total synthesis of protoporphyrin IX and its disodium salt using a new
      alternative method to the classical MacDonald condensation is reported. The key
      step is the reaction of the new unsymmetrical diiodo dipyrrylmethane 1 with the
      known dipyrrylmethane 2. Coupling of the two fragments leads directly to
      porphyrin 3 without the need of an oxidizing agent. The new methodology is well
      suited for the synthesis of protoporphyrin IX derivatives on a multi-100 g scale
      in good quality without the need for chromatography. Furthermore, these
      preparations are completely free of any contaminant of animal origin, which
      represents a real improvement in the manufacturing of protoporphyrin IX
      derivatives.

PMID- 23967690
TI  - Probing electronic dynamics during photochemical reactions.
AB  - This review discusses a new method for probing the evolution of the valence
      electron structure of molecules during chemical reactions. The method relies on
      the interaction of an intense infrared laser pulse with molecules that results in
      the emission of attosecond pulses (1 as = 10(-18) s) in a process known as high
      harmonic generation. Time-resolved high-harmonic spectroscopy measures the phase
      and amplitude of attosecond pulses emitted from the reacting molecules through
      interference with the emission from the unexcited molecules. This coherent
      detection mechanism provides a high sensitivity to small excitation fractions and
      direct access to both the amplitude and the phase of attosecond pulses, the
      latter of which is otherwise very difficult to measure. These observables reveal
      several complementary aspects of excited-state photochemical dynamics such as
      dissociation, adiabatic wave-packet evolution and conical intersection dynamics.

PMID- 23967691
TI  - Surface modification of biomaterials for conjugation with human fetal
      osteoblasts.
AB  - Surface functionalization of hydroxyapatite (HA) and beta-tricalcium phosphate
      (TCP) bioceramics with chemical ligands containing a pyrrogallol moiety was
      developed to improve the adhesion of bone cell precursors to the biomaterials.
      Fast and biocompatible copper-free click reaction with azido-modified human fetal
      osteoblasts resulted in improved cell binding to both HA and TCP bioceramics,
      opening the way for using this methodology in the preparation of cell-engineered
      bone implants.

PMID- 23967692
TI  - Local control theory using trajectory surface hopping and linear-response time
      dependent density functional theory.
AB  - The implementation of local control theory using nonadiabatic molecular dynamics
      within the framework of linear-response time-dependent density functional theory
      is discussed. The method is applied to study the photoexcitation of lithium
      fluoride, for which we demonstrate that this approach can efficiently generate a
      pulse, on-the-fly, able to control the population transfer between two selected
      electronic states. Analysis of the computed control pulse yields insights into
      the photophysics of the process identifying the relevant frequencies associated
      to the curvature of the initial and final state potential energy curves and their
      energy differences. The limitations inherent to the use of the trajectory surface
      hopping approach are also discussed.

PMID- 23967693
TI  - Nanopatterning by molecular self-assembly on surfaces.
AB  - The ability to pattern surfaces down to the nanoscale is of increasing importance
      in nanoscience research. The use of supramolecular chemistry to drive the
      formation of self-assembled networks allows for a bottom-up approach to achieve
      nanopatterned surfaces. This short review highlights some of the recent
      breakthroughs in achieving long-range order in such molecular based systems,
      complemented with examples from our own work. The tuning of molecular
      architectures can exert control on the emergent properties and function of
      molecules at interfaces. In particular the formation of porous honeycomb networks
      allows the rational design of highly ordered patterned surface domains and the
      investigation of molecular dynamics, chirality and templating effects on
      surfaces.

PMID- 23967694
TI  - Total synthesis of the myxobacterial macrolide ripostatin B.
AB  - This article describes the total synthesis of ripostatin B, which is a 14
      membered macrolide of myxobacterial origin that inhibits E. coli RNA polymerase
      by a different mechanism of action than the first-line anti-tuberculosis drug
      rifampicin. Structurally, ripostatin B features a labile and synthetically
      challenging doubly skipped triene motif embedded in the macrolactone ring. Key
      steps in the synthesis were a Paterson aldol reaction, a low-temperature
      Yamaguchi esterification and an alkene metathesis reaction to close the macrolide
      ring. The natural product was synthesized in a longest linear sequence of 21
      steps and 3.6% overall yield.

PMID- 23967695
TI  - Freeze-fracture shadow-casting (FreSCA) cryo-SEM as a tool to investigate the
      wetting of micro- and nanoparticles at liquid-liquid interfaces.
AB  - Since the seminal work of Pickering and Ramsden more than a century ago,
      adsorption of solid micro- and nanoparticles at the interface between two fluids
      has been recognized as a means to enormously improve emulsion stability against
      coalescence. Despite their long-standing use in a vast range of practical
      applications, several key issues regarding the behavior of small objects at
      liquid interfaces still remain unresolved. In particular, current techniques fail
      to investigate the properties of individual particles smaller than 500 nm. An
      exception to this scenario is a technique that we have recently developed, based
      on freeze-fracture cryo-SEM, which for the first time makes it possible to
      measure the wetting properties of single nanoscale objects through a metal shadow
      casting protocol. In this work we present additional details and results which
      showcase the potential of this novel tool as the benchmark for in situ
      characterization of particles at interfaces.

PMID- 23967696
TI  - Chiroptical properties of intrinsically chiral thiolate-protected gold clusters.
AB  - Chiral thiolate-protected gold clusters of atomic precision have gained
      increasing interest in recent years due to their potential use in catalysis,
      sensing or bioapplications. While the protection of gold clusters with chiral
      ligands is a rather trivial task, it was found that the clusters can bear
      intrinsically chiral features, most obvious in the arrangement of the protecting
      ligands on the surface of the cluster. Recent efforts showed the separation of
      the enantiomers of such intrinsically chiral gold clusters. This technique can be
      used for the prediction of chirality in structurally unknown clusters. Activation
      barriers for the racemization of Au38(SR)24 were determined. As this involves a
      huge rearrangement of the ligands, the flexibility of the gold-thiolate interface
      is demonstrated. Furthermore, the ligand exchange reactions between intrinsically
      chiral clusters and bidentate chiral thiols were studied. A limited,
      regioselective exchange was found. Most importantly, the reaction is
      diastereoselective and allows tailoring of gold clusters that are protected with
      a defined layer of ligands.

PMID- 23967697
TI  - Kinetic subpopulations detected by single-molecule spectroscopy: fundamental
      property of functional nucleic acids or experimental artefact?
AB  - Single-molecule spectroscopy allows the direct observation of conformational
      dynamics in individual biomolecules. Here, we describe how single-molecule
      Forster resonance energy transfer (smFRET) reveals heterogeneous kinetics in the
      EBS1*/IBS1* interaction, two RNA sequences that play an important role in group
      II intron mediated self-cleavage. Further examples of dynamic heterogeneity in
      functional nucleic acids are provided and the possible origins of this phenomenon
      are discussed.

PMID- 23967698
TI  - Practical considerations for improving the productivity of mass spectrometry
      based proteomics.
AB  - Mass spectrometry (MS) is currently the most sensitive and selective analytical
      technique for routine peptide and protein structure analysis. Top-down proteomics
      is based on tandem mass spectrometry (MS/ MS) of intact proteins, where multiply
      charged precursor ions are fragmented in the gas phase, typically by electron
      transfer or electron capture dissociation, to yield sequence-specific fragment
      ions. This approach is primarily used for the study of protein isoforms,
      including localization of post-translational modifications and identification of
      splice variants. Bottom-up proteomics is utilized for routine high-throughput
      protein identification and quantitation from complex biological samples. The
      proteins are first enzymatically digested into small (usually less than ca. 3
      kDa) peptides, these are identified by MS or MS/MS, usually employing collisional
      activation techniques. To overcome the limitations of these approaches while
      combining their benefits, middle-down proteomics has recently emerged. Here, the
      proteins are digested into long (3-15 kDa) peptides via restricted proteolysis
      followed by the MS/MS analysis of the obtained digest. With advancements of high
      resolution MS and allied techniques, routine implementation of the middle-down
      approach has been made possible. Herein, we present the liquid chromatography
      (LC)-MS/MS-based experimental design of our middle-down proteomic workflow
      coupled with post-LC supercharging.

PMID- 23967699
TI  - Lewis acid-water/alcohol complexes as hydrogen atom donors in radical reactions.
AB  - Water or low molecular weight alcohols are, due to their availability, low price
      and low toxicity ideal reagents for organic synthesis. Recently, it was reported
      that, despite the very strong BDE of the O-H bond, they can be used as hydrogen
      atom donors in place of expensive and/or toxic group 14 metal hydrides when boron
      and titanium(III) Lewis acids are present. This finding represents a considerable
      innovation and uncovers a new perspective on the paradigm of hydrogen atom
      transfers to radicals. We discuss here the influence of complex formation and
      other association processes on the efficacy of the hydrogen transfer step. A
      delicate balance between activation by complex formation and deactivation by
      further hydrogen bonding is operative.

PMID- 23967700
TI  - Extracting information about chemical bonding from molecular electron densities
      via single exponential decay detector (SEDD).
AB  - The recently introduced molecular descriptor (Single Exponential Decay Detector -
      SEDD) [P. de Silva, J. Korchowiec, T. A. Wesolowski, ChemPhysChem 2012, 13, 3462]
      is used to visualize bonding patterns in molecules. In each point of space SEDD
      is simply related to the electron density: SEDD(r) = In[1/rho2(del(del
      rho/rho)2)2]. Either experimental or computed densities rho(r) can be used to
      evaluate SEDD. Here, maps of SEDD are obtained from theoretical densities and
      reveal such features as core electrons, chemical bonds, lone pairs and
      delocalization in aromatic systems. It is shown that SEDD provides fingerprints
      of aromaticity, which can be separated into geometric and electronic effects.

PMID- 23967701
TI  - Precision measurements of ionization and dissociation energies by extrapolation
      of Rydberg series: from H2 to larger molecules.
AB  - Recent experiments are reviewed which have led to the determination of the
      ionization and dissociation energies of molecular hydrogen with a precision of
      0.0007 cm(-)1 (8 mJ/mol or 20 MHz) using a procedure based on high-resolution
      spectroscopic measurements of high Rydberg states and the extrapolation of the
      Rydberg series to the ionization thresholds. Molecular hydrogen, with only two
      protons and two electrons, is the simplest molecule with which all aspects of a
      chemical bond, including electron correlation effects, can be studied. Highly
      precise values of its ionization and dissociation energies provide stringent
      tests of the precision of molecular quantum mechanics and of quantum
      electrodynamics calculations in molecules. The comparison of experimental and
      theoretical values for these quantities enable one to quantify the contributions
      to a chemical bond that are neglected when making the Born-Oppenheimer
      approximation, i.e. adiabatic, nonadiabatic, relativistic, and radiative
      corrections. Ionization energies of a broad range of molecules can now be
      determined experimentally with high accuracy (i.e. about 0.01 cm(-1)).
      Calculations at similar accuracies are extremely challenging for systems
      containing more than two electrons. The combination of precision measurements of
      molecular ionization energies with highly accurateab initio calculations has the
      potential to provide, in future, fully reliable sets of thermochemical quantities
      for gas-phase reactions.

PMID- 23967702
TI  - 1,2,3-Triazoles as amide-bond surrogates in peptidomimetics.
AB  - 1,2,3-Triazoles represent a class of heterocycles with interesting properties for
      application in peptide sciences since they closely resemble amide bonds while
      being stable to enzymatic degradation. These characteristics make 1,2,3-triazoles
      promising candidates as amide-bond surrogates for the development of novel
      peptidomimetics with potentially improved biological characteristics. Despite the
      potential of the heterocycle as an amide-bond isoster, only few examples of
      triazole-based peptidomimetics can be found in the literature. With the intention
      to promote this new and promising strategy for peptide modification, this review
      summarizes synthetic methods available for the facile preparation of alpha-amino
      acid and alpha-amino alkyne building blocks and their use for the incorporation
      of 1,4-disubstituted 1,2,3 triazoles into the backbone of peptides mediated by
      the Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC). In addition, examples of
      the successful amide-to-triazole substitution in biologically active peptides are
      presented.

PMID- 23967703
TI  - [(Cp-R)M(CO)3] (M = Re or 99mTc) conjugates for theranostic receptor targeting.
AB  - Cyclopentadienyl complexes of 99mTc became accessible via a retro Diels-Alder
      synthetic approach of dimerized cyclopentadiene derivatives. So far, this
      approach was limited to derivatives comprising a carboxylic acid group, directly
      conjugated to the Cp-ring, leading to complexes [(C5H5COOH)99mTc(CO)3] and
      [(C5H5CONH-R)99mTc(CO)3], respectively. The introduction of an -NCO group via
      Curtius rearrangement and subsequent in situ reactions with alcohols or amines
      gave [(C5H5NHCO-OR)2] and [(C5H5NHCO-NHR)2]. To increase the spacer lengths
      between the Cp-ring and the functional groups, methylene and ethylene spacers
      were introduced to yield C5H5-CH2COOH and C5H5-C2H4COOH respectively. The latter
      Cp-derivatives reacted with [99mTcO4)]- and in the presence of CO
      releasing/reducing agents to the corresponding [(C5H5-spacer-COOH)99mTc(CO)3]
      complexes. The carboxylato groups can be derivatized with targeting functions,
      leading to structurally altered receptor binding complexes, with 99mTc for
      imaging and with rhenium for therapy. The nature of the 99mTc complexes was
      assessed by HPLC comparison with the corresponding rhenium compounds.

PMID- 23967704
TI  - Methane catalytic combustion on Pd9/gamma-Al2O3 with different degrees of Pd
      oxidation.
AB  - This research is focused on the analysis of adsorbed CH4 intermediates at
      oxidized Pd9 nanoparticles supported on gamma-alumina. From first-principle
      density functional theory (DFT) calculations, several configurations, charge
      transfer and electronic density of states have been analyzed in order to
      determine feasible paths for the oxidation process. Furthermore methane oxidation
      cycles have been investigated on Pd nanoparticles with different degrees of
      oxidation. In case of low oxidized Pd nanoparticles, activation of methane is
      observed, whereby hydrogen from methane is adsorbed at one oxygen atom. This
      reaction is exothermic. In a subsequent step, two water molecules desorb.
      Additionally, a very interesting structural effect becomes evident; Pd-carbide
      formation, which is also an exothermic reaction. Furthermore, oxidation of such
      carbidized Pd-nanoparticles leads to CO2 formation, which is an endothermic
      reaction. One important result is that the support is involved in the CO2
      formation. A different mechanism of methane oxidation was discovered for highly
      oxidized Pd nanoparticles. When the Pd nanoparticle is more strongly exposed to
      oxidative conditions, adsorption of methane is also possible, but it leads to
      carbonic acid production at the interface between the Pd nanoparticles and
      support. This process is endothermic.

PMID- 23967705
TI  - Bioinspired surfaces against bacterial infections.
AB  - Bioactive surfaces that can prevent bacterial infections are of great interest
      since device-related infections represent an emerging and major threat to our
      health-care system. For that purpose, dopamine and its derivatives have been
      shown to provide an exceptionally facile method for the immobilization of
      bioactive compounds on metal oxide surfaces through an operationally simple dip
      and-rinse procedure. Based on this method, three different coating strategies for
      the assembly of antifouling, antibacterial, and quorum sensing modulating
      surfaces have been established. The anachelin chromophore and nitro-dopamine
      proved to be very suitable anchoring moieties as they possess better oxidative
      stability and binding efficiency compared to dopamine itself. Furthermore,
      adsorbed bioactive hybrids were shown to be stable and recycling of the surfaces
      could be achieved. These examples clearly demonstrate the efficiency of this
      approach for the production of active surfaces, such as in biomedical devices.

PMID- 23967706
TI  - Peptide-catalyzed 1,4-addition reactions of aldehydes to nitroolefins.
AB  - Conjugate addition reactions of aldehydes to nitroolefins provide synthetically
      useful gamma-nitroaldehydes. Here we summarize our research on peptide-catalyzed
      conjugate addition reactions of aldehydes to differently substituted
      nitroolefins. We show that peptides of the general type Pro-Pro-Xaa (Xaa = acidic
      amino acid) are not only highly active, robust and stereoselective catalysts but
      have also remarkable chemoselectivities.

PMID- 23967707
TI  - Approaching two-dimensional polymers with macroscopic sizes.
AB  - We describe the challenges involved with extending the limited lateral size of
      two-dimensional polymers (2DPs). An amphiphilic monomer with three-fold symmetry
      is chosen to form an ideally tessellated monolayer at the air/water interface.
      Anthracene [4+4] photo-dimerization is chosen as the growth reaction. Formation
      of covalent net-points upon anthracene dimerization has an influence on the
      mechanical coherence of the resulting sheets which could be investigated
      qualitatively and quantitatively by means of AFM nano-indentation.

PMID- 23967708
TI  - New approaches to control infections: anti-biofilm strategies against gram
      negative bacteria.
AB  - Hospital-acquired bacterial infections, especially with Gram-negative pathogens,
      present a major threat due to the rapid spread of antibiotic-resistant strains.
      Targeting mechanisms of bacterial virulence has recently appeared as a promising
      new therapeutic paradigm. Biofilm formation is a bacterial lifestyle, which
      offers a survival advantage through its protective matrix against host immune
      defense and antibiotic treatment. Interfering with biogenesis of adhesive
      organelles, bacterial communication or carbohydrate-mediated adhesion as anti
      biofilm strategies are reviewed.

PMID- 23967709
TI  - Modeling and validation of heat and mass transfer in individual coffee beans
      during the coffee roasting process using computational fluid dynamics (CFD).
AB  - Heat and mass transfer in individual coffee beans during roasting were simulated
      using computational fluid dynamics (CFD). Numerical equations for heat and mass
      transfer inside the coffee bean were solved using the finite volume technique in
      the commercial CFD code Fluent; the software was complemented with specific user
      defined functions (UDFs). To experimentally validate the numerical model, a
      single coffee bean was placed in a cylindrical glass tube and roasted by a hot
      air flow, using the identical geometrical 3D configuration and hot air flow
      conditions as the ones used for numerical simulations. Temperature and humidity
      calculations obtained with the model were compared with experimental data. The
      model predicts the actual process quite accurately and represents a useful
      approach to monitor the coffee roasting process in real time. It provides
      valuable information on time-resolved process variables that are otherwise
      difficult to obtain experimentally, but critical to a better understanding of the
      coffee roasting process at the individual bean level. This includes variables
      such as time-resolved 3D profiles of bean temperature and moisture content, and
      temperature profiles of the roasting air in the vicinity of the coffee bean.

PMID- 23967710
TI  - Adsorption and microstructure of core-shell nanoparticles at liquid-liquid
      interfaces: an X-ray reflectivity study.

PMID- 23967711
TI  - Chemical Landmark 2012--designation of Rosental--the cradle of the Basel chemical
      industry and of the Novartis company archive.

PMID- 23967712
TI  - Genetics/genomics and drug effects.
AB  - Differences in response to medications both in terms of clinical activity and
      side-effects have long been recognised by physicians. Genetics has been recently
      considered as a potential factor to explain part of this variability.
      Pharmacogenetics focuses on the variants within one or more candidate genes while
      pharmacogenomics evaluates the entire genome for associations with pharmacologic
      phenotypes. Genetic variants can effect drug metabolism, drug transport or drug
      targets. Drug metabolism is responsible 1. for the conversion of prodrugs into
      active compounds or conversion of drug to toxic or inactive metabolites mostly
      through reactions mostly catalysed by cytochromes (CYP) P450 (phase reactions)
      and 2. for transforming drugs to compounds that are more water soluble and more
      easily excreted (phase type II reactions). Genetic polymorphisms can modify the
      activity of several CYPs such as CYPs, 2D6, 2C9, 2C19 with altered responses to
      codeine, tamoxifen, clopidogrel, warfarin, ... or of enzymes of the phase II
      reactions with abnormal responses to drugs like irinotecan, 5-fluorouracil,
      azathioprine, ... Proteins involved in the transport of drugs in or out the cells
      such as chemiotherapeutic agenrs, simvastatin, ... can also be affected by
      genetics. Genetics can also modify drug targets by mutations affecting tumour
      cells rending these later more or less responsive to drugs. Genetic tests have
      been launched for screening polymorphisms before giving drugs such as warfarin
      and several biomarkers are available in oncology. However, many challenges exist.
      For example, we need more prospective studies to have a better knowledge of the
      clinical impact and the cost-effectiveness of these tests. It remains that in the
      future pharmacogenetics/genomics will probably help to personalise medicine by
      conferring to the clinician the possibility of giving the right drug to the right
      patients and by this way improving efficacy and safety of medications.

PMID- 23967713
TI  - Evaluation of the appropriateness of intravenous amoxicillin/clavulanate
      prescription in a teaching hospital.
AB  - BACKGROUND: Despite the implementation of strategies aiming at improving
      antimicrobial utilisation, inappropriate use remains an increasing problem with
      important consequences on both antibiotic resistance and hospital costs.
      OBJECTIVE: To evaluate the appropriateness of prescribing the intravenous
      amoxicillin/clavulanate combination (Augmentin). METHODS: Prospective
      observational five-week study in a Belgian teaching hospital. Patients receiving
      prophylactic or therapeutic intravenous amoxicillin/clavulanate were enrolled.
      Data were collected by a pharmacist and the appropriateness of antibiotic
      treatment was analysed in collaboration with an infectious disease specialist
      according to local recommendations. The primary outcome measure was the
      appropriateness of indication, dosage, intravenous to oral switch and duration of
      therapy. RESULTS: One hundred and six patients were evaluated. The most common
      indications for amoxicillin/clavulanate prescriptions were: respiratory tract
      infections (38%), surgical/interventional prophylaxis (28%) and intra-abdominal
      infections (11%). Overall, 43% of intravenous amoxicillin/clavulanate
      prescriptions were fully appropriate. Indication for use was appropriate in 87%
      and dosage in 74% of cases. In contrast, the timing of intravenous to oral switch
      and duration of therapy were inappropriate in 64% and 53% of cases, respectively.
      CONCLUSIONS: This study identified two main areas for improving
      amoxicillin/clavulanate prescribing: (1) the intravenous to oral switch, which is
      often too late or nonexistent and (2) the duration of therapy, which is too long
      particularly in respiratory tract infections. The results have been presented to
      clinicians and specific interventions for optimisation are being discussed and
      implemented.

PMID- 23967714
TI  - Pain management in palliative cancer patients: a prospective observational study
      on the use of high dosages of transdermal buprenorphine.
AB  - INTRODUCTION: Despite guidelines and recommendations, a large proportion of
      patients with cancer still have inadequate pain control. Transdermal opioid
      administration can overcome problems such as swallowing and compliance, because
      only one application every three days is needed. Transdermal buprenorphine was
      documented to provide effective pain relief in cancer and non-cancer patients. A
      ceiling effect was described in animals at supratherapeutic dose levels.
      OBJECTIVES: This prospective observational pilot study was designed to explore
      the need for doses of transdermal buprenorphine beyond the recommended maximum
      dose of 140 microg/h, in a cohort of palliative patients with cancer pain.
      METHODS: 36 consecutive palliative patients with uncontrolled cancer pain were
      prescribed transdermal buprenorphine after having received adequate information
      on the disease, its evolution, the pain and the drug. They gave written informed
      consent for participation in this observational study. Pain intensity and use of
      breakthrough medication were registered by the patient and the health care
      provider. RESULTS: Pain was judged to be satisfactory controlled, by the patient
      and the health care providers, in 21 of 28 evaluable patients at a dose lower
      than or equal to 140 microg/h. The success rate was higher in the hospitalized
      patient group. The observation of adequate pain control in two patients treated
      with doses up to 210 microg/h supports the hypothesis that buprenorphine dose
      titration above 140 microg/h can be clinically effective and well tolerated. This
      also refutes the assumption of a clinically relevant ceiling effect. CONCLUSIONS:
      Transdermal buprenorphine control cancer pain in the majority of palliative
      patients.

PMID- 23967715
TI  - Prognosis of HIV infected sub-Saharan patients on renal replacement therapy (RRT)
      in Brussels, Belgium: a single centre retrospective pilot study and review of the
      literature.
AB  - BACKGROUND: Few data exist documenting the survival experience of immigrated sub
      Saharan patients infected by the human immunodeficiency virus (HIV) on renal
      replacement therapy (RRT). METHODS: This retrospective single centre pilot study
      includes 105 consecutive patients of sub-Saharan origin who started RRT in our
      unit, between January 1986 and April 2010. The aim was to analyse the
      characteristics and the survival rate on RRT of these patients. RESULTS: Out of
      105 patients 81/105 (77%) were HIV-negative and 24/105(23%) were HIV-positive.
      HIV-positive patients were younger than HIV-negative patients and they were more
      often treated with peritoneal dialysis (PD) (21/24) than with haemodialysis (HD).
      Dialysis peritonitis was equally distributed between HIV-positive and HIV
      negative patients. Because of opportunistic infections, duration of
      hospitalisation was longer for HIV-positive than for HIV-negative patients. In PD
      treated patients, the number of hospitalisations tended to be greater in patients
      who experienced at least one peritonitis episode and the duration of
      hospitalisation also tended to be longer. The survival rate was better in
      patients younger than 50 years and in patients on HD, but was similar for both
      positive and negative HIV patients. CONCLUSIONS: To the best of our knowledge,
      these are the first data concerning patients who have emigrated from sub-Saharan
      Africa to Belgium, and who are on RTT. Their survival rate is better if they are
      younger than 50 years and on HD. As the majority of HIV patients were treated by
      PD in our center, a conclusion regarding survival on different dialysis
      modalities is not possible for this group of patients. Survival rates were
      similar for HIV-positive and HIV-negative patients despite longer duration of
      hospisalization for HIV-positive patients.

PMID- 23967716
TI  - Longitudinal economic consequences of colorectal cancer in a university hospital
      setting.
AB  - BACKGROUND: Colorectal cancer is an important cause of morbidity and mortality in
      Europe. Medical interventions improve health outcomes, but may come at a
      considerable cost for the health care system and for patients. There is a need
      for so called incidence-based cost-analyses, in order to better understand the
      potential impact of new types of prevention and treatment. AIM: The objective of
      this study was to map--both from the patient and the health insurance perspective
      -the longitudinal costs of colorectal cancer in a university hospital setting. In
      addition, the average monthly cost per patient and the costs during the last year
      of life were investigated. METHODS: The incidence-based analysis was conducted on
      data from 539 patients, who were treated for colorectal cancer in the Ghent
      University Hospital between July 1989 and August 2008. Data were obtained from
      all identified invoices and analysed from the perspective of both the health
      insurance and the patient. The costs were split in three major categories: drugs,
      hospital stay and fees. The follow-up period was divided into three periods:
      before recurrence, between recurrence and metastatic disease, and from metastatic
      disease until death. RESULTS: The total cumulative cost for an average follow-up
      of 3 years and 3 months was Euro37,696.2, the cost for rectal cancer and colon
      cancer being similar (Euro38,058 versus Euro37,268 respectively). Patients pay on
      average 10% of the cost, whereby medical fees are the main contributor to this
      cost. The total cost for patients who died during followup is higher (p = 0.297)
      compared to the cost in those who were still alive at the end of the follow-up
      period. The costs are highest during the last year of life. There was a
      significant difference (p = 0.049) in costs between patients with (Euro41,256.4)
      and without (Euro35,525.4) involved Lymph Nodes (LN) at the time of diagnosis.
      CONCLUSION: This study provides insight in the total longitudinal costs of
      colorectal cancer, and on the drivers of these costs within pre-defined periods
      in the progress of the disease. Taking into consideration some inherent
      limitations of our data and methods, such data are relevant and informative to
      health care policy makers and should be investigated more frequently.

PMID- 23967717
TI  - Imported malaria in a tertiary hospital in Belgium: epidemiological and clinical
      analysis.
AB  - BACKGROUND AND OBJECTIVE: There has been a marked increase in tourism,
      immigration, and business travel to malaria-endemic areas. Non-immune individuals
      (western travellers) or immigrants living for more than one year in non-endemic
      areas who visit friends and relatives (VFR) are particularly susceptible to
      developing severe malaria when travelling to areas with high levels of
      transmission. In this study, epidemiological, clinical and biological features of
      malaria in travellers returning from endemic areas were analysed. This may help
      clinicians unfamiliar with malaria not to overlook this disease in its early
      stage, and to initiate prompt treatment. PATIENTS AND METHODS: We retrospectively
      analysed all cases of patients who presented with malaria in our institution
      between 2003 and 2008. RESULTS: Eighty patients were included. Most patients
      visited Africa (93.6%). Accordingly, P. falciparum was the main species
      identified (67/77 patients i.e. 87%). Sixty-five patients (65/78 i.e. 83.3%) had
      not taken any prophylaxis and 13 (16.7%) had taken it inadequately. Common
      clinical features were fever (80/80, 100%), influenza-like symptoms (16/80,
      20.1%), respiratory symptoms (5/80, 6.3%), neurological symptoms (2/80, 2.5%) or
      digestive symptoms (15/80, 18.8%). Digestive symptoms were predominant in
      children < 16 y.o. (60% of these patients). CONCLUSION: Imported malaria cases
      are mostly related to the lack of adequate use of chemoprophylaxis. Plasmodium
      falciparum is the main species responsible for imported cases of malaria in our
      institution. Clinical features vary, but fever is universally present at
      presentation. As such, all cases of fever upon return from a malaria-endemic area
      must be considered as malaria until proven otherwise, at least during the first
      three months after the return.

PMID- 23967718
TI  - Prevalence of orthostatic hypotension and relationship with drug use amongst
      older patients.
AB  - INTRODUCTION: Orthostatic hypotension (OH) is said to be highly prevalent in
      older people. Drugs are often involved as causative factor. Nevertheless, few
      data are available about the prevalence of OH and its relationship with drugs in
      olders. OBJECTIVES: To review data about (i) the prevalence and characteristics
      of OH in older patients; and (ii) the relationship between OH and drugs. METHODS:
      Review of publications from Ovid (PubMed) from 1980 to May 2011 using the
      following key words: "orthostatic hypotension" combined with "elderly" or
      equivalent for the analysis of prevalence (first search) and "orthostatic
      hypotension" combined with "drugs" or equivalent to assess the relationship
      between OH and drugs (second search). RESULTS: Fifty-one publications (of which
      14 with original data) were retrieved from the prevalence search, 31 for the
      second search (8 with original data: 7 retrospective studies and 1 prospective
      cohort study) and 12 reviews or experts opinions. Prevalence of OH varies
      according to the characteristics of the subjects, the settings of the studies,
      and the procedures of blood pressure measurement. In acute geriatrics units, two
      studies reported a prevalence of over 30% and one study mentioned that 68% of the
      patients presented with at least one episode during the day. OH was associated
      with several geriatric problems: gait disorders, balance disorders, falls,
      cerebral hypoperfusion, transient ischemic attacks, cognitive impairment, acute
      myocardial infarct and systolic hypertension. OH can also be asymptomatic or with
      atypical presentation: falls, gait disorders and confusion. Psychotropic agents
      (antipsychotics, sedatives, antidepressants), and cardiovascular drugs
      (antihypertensive agents, vasodilators, diuretics) were associated with OH.
      DISCUSSION: If the hypothesis of causality between drug treatment and OH is
      confirmed, the identification of the involved drugs could be of value for the
      prevention of OH and its complications. In this context, the Working Group
      Pharmacology Pharmacotherapy and Pharmaceutical Care of the Belgian Society of
      Gerontology and Geriatrics proposes to conduct a multicentre study to assess the
      prevalence of OH in Belgian acute geriatrics units and its relationship with
      drugs.

PMID- 23967719
TI  - Ergotamine-induced pleural and pericardial effusion successfully treated with
      colchicine.
AB  - A 83-year-old woman was admitted to hospital with chest pain, fever, dry cough
      and palpitations. Chest X-ray revealed a pleural effusion, assumed to be caused
      by cardiac failure and respiratory infection. Despite treatment with antibiotics
      and diuretics, the pleural effusion increased on chest X-ray and there were signs
      of pleural and pericardial effusion on computed tomography (CT) scan. Treatment
      with non-steroidal anti-inflammatory drugs (NSAIDs) was not successful. Meanwhile
      patients' long-term use of ergotamine for migraine was revealed, which is
      associated with pleuropulmonary and cardiac fibrotic reactions. Tentative
      treatment with colchicine was successful, with complete resolution of pleural
      fluid, fever, cough and inflammatory parameters. This case highlights the
      importance of establishing an ergot alkaloid use registry in unexplained
      pleuropericardial effusions and supports the use of colchicine as a potential
      therapeutic approach.

PMID- 23967720
TI  - Calciphylaxis: a rare complication in alcoholic liver disease.
AB  - Calciphylaxis, or calcific uremic arteriolopathy (CUA) is a rare but well
      described entity in patients with endstage renal disease (ESRD) and/or
      hyperparathyroidism. CUA is characterized by systemic acute calcification of the
      small and intermediate dermal vasculature that can lead to epidermal ischemia,
      ulceration, and necrosis. Cutaneous lesions of calciphylaxis characteristically
      begin as tender, violaceous, livedoid discolorations. The mechanisms of disease
      remain poorly understood although abnormal bone and mineral metabolism and
      hyperparathyroidism can contribute to CUA. Therapeutic strategies are of unproven
      benefit and mortality remains high. Calciphylaxis has also been extremely rarely
      reported in patients without ESRD and/or hyperparathyroidism. We report an
      unusual case of calciphylaxis in a patient with alcoholic liver cirrhosis and
      normal renal function, without any alteration in the phosphocalcic and
      parathyroid hormone (PTH) metabolisms.

PMID- 23967721
TI  - Unusual cause of severe anaemia in a patient with metastatic haemangiopericytoma.
AB  - Haemangiopericytoma is a rare tumor of vascular origin. We report the case of
      patient with severe refractory anaemia due to peripheral destruction of red blood
      cells by spleen metastases. Anaemia was successfully treated by splenectomy.
      Afterwards, our patient developed liver and lung metastases and was treated, in a
      clinical trial, with gefitinib that stabilised the disease during nine years.
      These interesting features are discussed.

PMID- 23967722
TI  - Relapsing visceral leishmaniasis in a HIV-1 infected patient with advanced
      disease.
AB  - Leishmaniasis, an intracellular protozoal infection in which tissue macrophages
      are targeted, is transmitted by female sandfly bite and occurs in 98 countries.
      Visceral leishmaniasis (VL) is the clinical form of leishmaniasis most frequently
      associated with HIV, especially in Europe. Both diseases have a synergistic
      detrimental effect on the cellular immune response. Treatment of VL in patients
      with underlying HIV-infection is associated with lower cure rates, higher rates
      of drug toxicity, higher relapse rates and greater mortality than treatment of VL
      in immunocompetent patients. We report the case of a HIV-1 infected patient with
      advanced disease who presented VL with multiple relapses. This case highlights
      the difficulties of treating VL in patients with HIV co-infection.

PMID- 23967723
TI  - Chronic wounds in a kidney transplant recipient with moderate renal impairment.
AB  - Calcific uremic arteriolopathy (CUA) or calciphylaxis is a condition
      predominantly observed in patients with end-stage kidney disease characterized by
      small vessel calcification, intimal proliferation, endovascular fibrosis and
      intravascular thrombosis causing down-stream infarction predominantly of skin
      resulting in extremely painful necrotic ulceration. Several interventions have
      been proposed in an attempt to attenuate the high mortality associated with CUA.
      One of the most promising therapeutic approaches is the administration of sodium
      thiosulfate which is able to chelate cations such as calcium and in this way
      possibly dissolving tissue calcium deposits into more hydrophilic calcium
      thiosulfate. Due to the scarcity of reports of CUA patients treated with sodium
      thiosulfate the safety profile of this drug is not (well) established at this
      moment especially in patients not receiving kidney replacement therapy. Here, we
      describe a case of a kidney transplant recipient with CUA and moderately declined
      kidney function who was treated with sodium thiosulfate and developed important
      hypernatremia and high anion gap acidosis necessitating significant reduction in
      dosing.

PMID- 23967724
TI  - Papain-induced asthma: a man with dyspnea from dawn till dust.
AB  - A 52-year-old man, a current smoker (40 pack years) with unremarkable medical
      history, was referred to the outpatient pneumology clinic because of recent
      complaints of shortness of breath and wheezing, which were relieved by inhaled
      bronchodilators. Serial peak expiratory flow (PEF) measurements showed a clear
      rise in PEF during the weekend and a fall on the evening after the first day of
      the week. It also showed that evening values were always lower than morning
      values. During a holiday, a slow but persistent rise in PEF was observed. Such a
      pattern is highly suggestive for occupational asthma. A detailed description of
      his job revealed papain exposure. After a positive specific IgE and skin prick
      test for papain the diagnosis of papain induced asthma was made. When an allergy
      and serious lung function impairment is proven against products encountered in a
      work related situation, not improving after maximal preventive measures, the
      patient is advised to change job.

PMID- 23967725
TI  - Autoimmune haemolytic anaemia in a patient treated with capecitabine.
AB  - A 61-year-old female, followed-up for a metastatic breast cancer, was admitted in
      our institution with conjunctival icterus, asthenia and abdominal crampoid pain.
      The patient was included in a clinical trial comparing the efficiency of
      capecitabine monotherapy versus capecitabine conjugated with a new biological
      agent in a randomised and double blind trial. The patient was in the capecitabine
      alone arm. Biological tests performed upon admission suggested the diagnosis of
      haemolytic anaemia. Moreover, the direct Coombs test result was twice positive
      indicating autoimmune haemolytic anaemia. Capecitabine has been reported to cause
      haemolysis either alone or combined with lapatinib, each time with a mechanism
      other than immunological. In this clinical case, capecitabine is the most likely
      factor causing an autoimmune haemolytic anaemia.

PMID- 23967726
TI  - An unusual case of acute psychosis in an adolescent.
AB  - Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a severe form of
      encephalitis that has been identified within the context of acute
      neuropsychiatric manifestations. We report the case of an 18-year-old adolescent
      referred for a first episode of acute psychosis. The clinical picture rapidly
      deteriorated to a state of catatonia, decreased consciousness and autonomic
      instability. Detection of highly positive anti-NMDA-R antibodies confirmed the
      diagnosis of anti-NMDA-R encephalitis. Immunosuppressive treatment and repeated
      plasma exchange resulted in slow recovery. The literature on diagnosis and
      treatment of this specific type of encephalitis is reviewed.

PMID- 23967727
TI  - Basophil activation in the diagnosis of life-threatening hypersensitivity
      reaction to iodinated contrast media: a case report.
AB  - Hypersensitivity to iodinated radiologic contrast media occurs in 1-3% of
      patients. A complete allergological work-up requires the identification of the
      pathogenetic mechanism as well as the identification of safe alternatives. The
      current diagnostic approach relies upon skin tests, since no other in vitro test
      is standardized. However skin tests do not have an absolute predictive value,
      cannot be executed immediately and may expose the patients to the risk of severe
      reactions. Recently the flow-cytometric evaluation of activated basophils, also
      known as basophil activation test (BAT) has been introduced. Our case report of a
      28-year old female who experienced an anaphylactic shock immediately after
      administration of iomeprol supports the role of BAT in the diagnosis and
      management of hypersensitivity reactions to contrast media. The possibility of
      shortening the diagnostic work-up without endangering the health of patients
      represents the main advantage of this test.

PMID- 23967728
TI  - Chronic necrotising aspergillosis mimicking ACTH-secreting tumour in a case of
      Cushing's disease.
AB  - An 18-year-old man presenting with speech and behaviour disorders was found to
      suffer from Cushing's syndrome. Ectopic ACTH secretion was initially suspected on
      the basis of very high cortisoluria and ACTH concentrations, severe hypokalemia,
      a lung hypermetabolic lesion and a normal pituitary on conventional magnetic
      resonance imaging (MRI). After lung surgery, this lesion proved to be chronic
      necrotising aspergillosis (CNA). Diagnostic reevaluation by bilateral inferior
      petrosal sinus sampling disclosed a right-sided petrosal sinus gradient
      consistent with Cushing's disease (CD). A new high resolution thin-section MRI
      demonstrated a 5 mm pituitary adenoma, which could be removed successfully. Thus,
      a lung mass associated with several clues in favour of ectopic ACTH secretion may
      hide a diagnosis of CD. Such a mass can be CNA, an opportunistic infection
      favoured by immunosuppression, which to our knowledge, is the first case reported
      in CD.

PMID- 23967729
TI  - Rectus sheath haematoma: enoxaparin-related complication.
AB  - Rectus sheath haematoma, an uncommon complication related to subcutaneous
      administration of enoxaparin, has overall mortality of 4%. Possible mechanisms
      include unintended intramuscular injection of enoxaparin, and enhanced
      anticoagulant effect in the elderly and patients with increased bleeding risk. We
      describe the case of an 80 year-old female patient who was treated after a non-ST
      elevated myocardial infarction, with enoxaparin, aspirin and clopidogrel. After a
      single dose of enoxaparin, the patient developed massive rectus sheath haematoma
      that was promptly diagnosed and was surgically managed. The patient recovered
      uneventfully. With incremented use of low-molecular weight heparins in the
      elderly, one may expect a growing number of bleeding complications.

PMID- 23967730
TI  - Pseudo-tumoural sarcoidosis.

PMID- 23967731
TI  - A rare cause of hyperferritinemia without iron overload.

PMID- 23967732
TI  - [Persistent attention on chronic hepatitis B clinical study].

PMID- 23967733
TI  - [What is new in 2012 on hepatitis C].

PMID- 23967734
TI  - [Advances in hepatocellular carcinoma research 2012].

PMID- 23967735
TI  - [Advance of diagnosis and management of fatty liver disease in 2012].

PMID- 23967736
TI  - [Acute kidney injury and hepatorenal syndrome in end stage liver disease].

PMID- 23967737
TI  - [Diagnostic and treatment guidelines for liver failure (2012 version)].

PMID- 23967738
TI  - [Clinical efficacy of various antiviral-based strategies to treat chronic
      hepatitis patients with positivity for hepatitis B e antigen and rtN236T
      mutation].
AB  - OBJECTIVE: To compare the efficacy and safety of the common antivirals, including
      adefovir dipivoxil (ADV), pegylated-interferon alpha-2a (peg-IFN) and lamivudine
      (LAM), used as combination therapies to treat chronic hepatitis B (CHB) patients
      with positivity for the hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV)
      harboring the ADV-resistance mutation, rtN236T, and to explore the factors
      associated with curative outcome. METHODS: Sixty-five adult CHB patients (age
      range: 20-60 years) who were unresponsive to ADV therapy (HBeAg-positive; HBV DNA
      >or= 10(5) copies/ml), LAM-naive, and tested positive for the rtN236T HBV
      mutation were enrolled in the study and randomly divided into two treatment
      groups: Group A (n = 33), who were administered ADV (10 mg/day, orally) plus peg
      IFN (180 microg/week, subcutaneous injection) for 48 weeks; and Group B (n = 32
      patients), who received the ADV plus LAM (100 mg/day, orally) for 48 weeks
      followed by continued LAM treatment for an additional 24 weeks. Pre- (baseline),
      during and post-treatment measurements of HBV viral loads and hepatitis B markers
      were made by quantitative PCR and electrochemiluminescence assays, respectively.
      All patients underwent liver biopsies to determine the histological activity
      index (HAI) and treatment response regarding inflammation and fibrosis stage. The
      rates of virological response (VR), HBeAg-negativity, HBeAg seroconversion, and
      alanine aminotransferase (ALT) normalization were calculated, and the
      significance of differences between groups were assessed by Student's t-test and
      Chi2 test. RESULTS: There were no significant differences between the two groups
      in regards to sex, age, or baseline levels of HBV DNA, ALT, and total bilirubin
      (P > 0.05). At weeks 24 and 48 of treatment and 24 after treatment end, group A
      showed significantly higher (vs. group B, P < 0.05) rates of reduced HBV DNA
      viral loads (81.8%, 90.9%, and 75.8% vs. 53.1%, 56.2%, and 59.4%), VR (48.5%,
      60.6%, and 42.4% vs. 31.3%, 34.4%, and 31.3%), HBeAg-negativity (39.4%, 60.6%,
      and 54.5% vs. 12.5%, 37.5%, and 37.5%), HBeAg seroconversion (27.3%, 54.5%, and
      48.5% vs. 6.3%, 15.6%, and 18.8%), and ALT normalization (72.7%, 84.8%, and 78.8%
      vs. 46.9%, 56.3%, and 46.9%). After 48 weeks of treatment, group A showed
      significantly improved HAI (vs. group B, P < 0.05). With the exception of
      treatment-related increased creatinine (P < 0.05), group A showed significantly
      higher rates of adverse reactions; although, none was serious enough to threaten
      patient safety or necessitate early termination of the treatment regimen. Twenty
      four weeks after treatment completion, five patients had HBV viral loads of >or=
      2log10 copies/ml and four had < or= 500 copies/ml, and ALT was normalized in 28
      patients. The four patients in group A with HBV DNA < or= 500 copies/ml and
      elevated ALT during treatment did not show HBeAg seroconversion. CONCLUSION: Peg
      IFN plus ADV combination therapy produced better outcomes than the ADV plus LAM
      combination therapy in regards to HBV viral loads, VR rate, HBeAg-negative rate,
      HBeAg seroconversion rate, ALT normalization rate, and HAI, but was associated
      with a higher rate of adverse reactions (none of which were severe). Lack of
      HBeAg seroconversion was associated with higher virus load and ALT levels.

PMID- 23967739
TI  - [Epidemiological and clinical features of occult hepatitis B in HIV infection
      without antiretroviral treatment].
AB  - OBJECTIVE: To investigate and analyze the differential prevalence, as well as the
      risk factors and clinical features, of occult hepatitis B virus (HBV) infection
      in the human immunodeficiency virus (HIV)-infected population without
      antiretroviral therapy (ART) as compared to the general (non-HIV-infected)
      population. METHODS: Two-hundred-and-forty-eight individuals with confirmed HIV
      infection but ART naive (males: 220, females: 28; 15-82 years old) were enrolled
      in the study, along with 121 healthy individuals (confirmed HIV antibody
      negative; males: 53, females: 68; 20-88 years old). HBV markers (hepatitis B
      surface antigen (HBsAg); hepatitis B e antigen (HBeAg); anti-HBs, anti-HBe and
      anti-hepatitis B core (HBc) antibodies) were detected by microparticle enzyme
      linked immunosorbent assay (AxSYM immunology analyzer manufactured by Abbott
      Laboratories); all cases and controls were confirmed negative for hepatitis B
      surface antigen (HBsAg). Then, the HBV DNA level in serum was detected using
      nucleic acid amplification assay (COBAS AmpliPrep/COBAS TaqMan HBV test, version
      2.0 manufactured by Roche). CD4+ T lymphocytes were measured by flow cytometry,
      and alanine aminotransferase (ALT, marker of liver function) was measured by
      enzymatic assay. RESULTS: Twenty-four of the HIV cases (9.7%) and four of the
      healthy controls (3.3%) tested positive for HBV DNA; the amount of individuals
      with HBV DNA-positivity was significantly higher in the HIV-infected group (P =
      0.035). Among the 24 cases of HBV DNA(+) HIV-infected individuals, the lowest HBV
      DNA load was < 20 IU/ml and the highest was 3.22 x 10s IU/ml; nine of the
      individuals (37.5%) had HBV DNA load > 100 IU/ml, four (16.7%) had 20-99 IU/ ml,
      and 11 (45.8%) had < 20 IU/ml. Among the total HIV-infected cases with HBV DNA
      positivity, 7.3% (8/110) were anti-HBc(+)/anti-HBs(+), 20.8% (11/53) were anti
      HBc(+)/anti-HBs(-), 14.3% (3/21) were anti-HBc(-)/anti-HBs(+), and 3.1% (2/64)
      were anti-HBc(-)/anti-HBs(-). The amount of individuals with HBV DNA-positivity
      in the anti-HBc(+)/anti-HBs(-) group was significantly different from those in
      the anti-HBc(+)/anti-HBs(+) group (P = 0.018) and the anti-HBc(-)/anti-HBs(-)
      group (P = 0.003). However, multiple comparison of HBV DNA loads detected between
      the four groups of HBV marker status revealed no significant difference (P =
      0.805). Furthermore, statistical analysis provided no evidence to support that
      occult hepatitis B infection in HIV-infected individuals had any impact on CD4+ T
      lymphocytes count (Z = 1.902, P = 0.059) or ALT levels (Z =1.401, P = 0.161).
      CONCLUSION: HIV-infected individuals who are ART naive and HBsAg(-) have a higher
      incidence of HBV DNA-positivity than individuals in the general (non-HIV
      infected) population. In addition, the highest rate of occult hepatitis B among
      the HIV-infected cases occurred among individuals who were anti-HBc(+)/anti-HBs(
      ).

PMID- 23967740
TI  - [Comparative analysis of electro-chemiluminescence immunoassay and
      chemiluminescent microparticle immunoassay abilities to quantitatively assess
      hepatitis B surface antigen].
AB  - OBJECTIVE: To perform a systematic comparative analysis of two different
      commercial automated systems using chemiluminescence immunoassay to
      quantitatively detect hepatitis B virus surface antigen (HBsAg) in patient sera.
      METHODS: The Elecsys2010 electrical chemiluminescence immunoassay (ECLIA;
      manufactured by Roche) and the ARCHITECT il000 chemiluminescence magnetic
      microparticle immunoassay (CMIA; manufactured by Abbott) were used to detect
      HBsAg in 100 serum samples of individuals who presented at our department with
      suspected hepatitis infection between January and May 2012. The manufacturer's
      protocols were strictly followed. The categorical data was analyzed by Chi
      squared test, and linear regression analysis was used to compare the results of
      the two assay systems. RESULTS: The HBsAg detection results from the two
      different assay systems showed good correlation (r >or= 0.95), and had good
      correlation at a low (r = 0.966), medium (r = 0.974) and high (r = 0.984) cutoff
      values. However, the positive detection rate of CMIA was significantly higher
      than that of ECLIA(94% vs. 88%, P < 0.05). When the HBsAg content was below 0.10
      IU/ml, the ECLIA detection rate and sensitivity were slightly higher than those
      of CMIA. CONCLUSION: The ARCHITECT i1000 and Elecsys 2010 immunoassay systems
      have good correlation in quantitative detection of HBsAg, but the former may be
      more sensitive.

PMID- 23967741
TI  - [Dynamic changes in PD-1, TLR3, and TLR4 surface expression on peripheral blood
      mononuclear cells in chronic hepatitis C patients undergoing peg-IFNalpha-2a plus
      ribavirin combination therapy].
AB  - OBJECTIVE: To investigate the dynamic changes in expression of programmed death
      (PD)-1, Toll-like receptor (TLR)3, and TLR4 on the surface of peripheral blood
      mononuclear cells (PBMCs) in patients with chronic hepatitis C (CHC) that occur
      in response to pegylated-interferon alpha-2a (peg-IFNalpha-2a) plus ribavirin
      (RBV) combination therapy, and to analyze the relation to achievement of
      sustained virological response (SVR). METHODS Twenty-three CHC patients and 10
      healthy controls were enrolled in the study. All CHC patients underwent 48 weeks
      of combination therapy with peg-IFNalpha-2a (180 microg, subcutaneous injection,
      once weekly) plus RBV (15 microg/kg, oral, once daily). Total PBMCs were isolated
      from both groups (CHC patients at treatment week 0, 12, 24, and 48 and post
      treatment week 24; controls at enrollment) and subjected to flow cytometric
      analysis of PD-1, TLR3, and TLR4 surface expression. In addition, serum levels of
      alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels were
      analyzed by enzymatic assay and the AmpliPrep/COBAS (Roche) nucleic acid
      amplification test, respectively. SVR was defined as undetectable levels of HCV
      RNA at post-treatment week 24. Intergroup differences were assessed by one-way
      ANOVA. RESULTS: The expression ratios of PD-1, TLR4 and PD-1: TLR4 on PBMCs were
      significantly higher in CHC patients before therapy than in the healthy controls
      (45.20 +/- 7.12% vs. 16.82 +/- 4.13%, 58.45 +/- 15.13% vs. 21.09 +/- 2.89%, and
      35.54 +/- 7.69% vs. 14.12 +/- 2.89%; all P < 0.05). In contrast, the expression
      ratios of TLR3 and PD-1:TLR3 were slightly, but not significantly, higher in CHC
      patients before therapy than in the healthy controls (P > 0.05). During the
      course of peg-IFNalpha-2a plus RBV combination therapy, the expression ratios of
      PD-1 and TLR4 on PBMCs showed a decreasing trend, while TLR3 expression showed an
      increasing trend. Furthermore, CHB patients who achieved SVR at post-treatment
      week 24 had a significantly different expression ratio of PD-1 and TLR3 than
      those who did not achieve SVR (P < 0.05). CONCLUSION: Surface expression of PD-1,
      TLR4, and PD-1:TLR4 is up-regulated in the total PBMCs of CHC patients. Peg
      IFNalpha-2a plus RBV treatment-induced suppression of HCV replication results in
      a significant reduction in PD-1 and TLR4 expression on the surface of PBMCs, but
      a remarkably elevated level of TLR3 expression. The dynamic change in PD-1 and
      TLR3 expression on PBMCs that occurs during antiviral therapy may be related to
      achievement of SVR.

PMID- 23967742
TI  - [Prospective study on the relation between serum vitamin D levels and liver
      cirrhosis risk].
AB  - OBJECTIVE: To explore the relation between serum vitamin D (25(OH)D)
      concentrations and liver cirrhosis. METHODS: A nested case control study was
      designed based on the Nutrition Intervention Trial (NIT) cohort, from which non
      degraded serum samples and complete baseline and follow-up data were available
      for 282 individuals diagnosed with liver cirrhosis and 564 healthy controls. The
      serum samples were tested by enzyme-linked immunosorbent assay to detect and
      quantify 25(OH)D, as well as hepatitis B virus surface antigen and core antibody
      and hepatitis C virus antibody. The study participants were divided into four
      groups according to quartile range of 25(OH)D concentration and logistic
      regression modeling was used to evaluate the relation with liver cirrhosis risk
      by estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The
      liver cirrhosis group had a significantly lower concentration of 25(OH)D than the
      control group (median and quartile range in nmol/L, cases: 15.3 and 13.8;
      controls: 20.2 and 16.6; t = 5.169, P = 0.002). When the first interval was set
      as the reference level, the ORs(95% CIs) of the second, third, and fourth
      intervals were: 0.495(0.333 - 0.736), 0.452(0.303 - 0.675), and 0.349(0.231-
      0.527). After adjusting the analysis for the presence of pathogenic-related
      confounding factors, the ORs(95% CIs) of the second, third, and fourth intervals
      were: 0.499(0.328 - 0.759), 0.427(0.278 - 0.654), and 0.344(0.222-0.532). The
      25(OH)D level was inversely correlated with risk of liver cirrhosis (Chi2 =
      25.200, P < 0.001). CONCLUSION: Risk of liver cirrhosis increases as 25(OH)D
      serum concentration decreases. Vitamin D might function as a protective factor
      against development of cirrhosis.

PMID- 23967743
TI  - [Establishment of a complex alcoholic liver fibrosis mouse model and
      investigation of OPN and TGF-beta1 hepatic expression].
AB  - OBJECTIVE: To create a convenient method to establish an alcoholic liver fibrosis
      model in mice and use it to explore the putative pathogenic mechanisms involving
      the immunomodulatory proteins osteopontin (OPN) and transforming growth factor
      betal (TGF-beta1). METHODS: Forty C57BLI6J mice were fed the Lieber-DeCarli 4%
      ethanol-containing liquid diet for four weeks, followed by an additional four
      weeks of the 4% ethanol diet combined with intraperitoneal injection of carbon
      tetrachloride (CC14 5% solution in olive oil; 2ml/ kg body weight, 2 times/week)
      to induce alcoholic liver fibrosis. Control groups (n = 6 each) included: normal
      diet; normal diet plus CCl4 injections; ethanol diet alone; ethanol diet plus
      solvent (olive oil) injections. Model establishment was monitored by sacrificing
      six mice at model inception (week 0), and weeks 4, 5, 6, 7, and 8 of modeling to
      collect liver tissues and blood for histological and biochemical analyses. Extent
      of hepatic steatosis, inflammation, and fibrosis was assessed by hematoxylin
      eosin and Masson staining. Liver function markers, serum alanine aminotransferase
      (ALT) and aspartate aminotransferase (AST) levels, were tested by automated
      enzymatic assays. Alpha-smooth muscle actin (alpha-SMA) expression was detected
      by immunohistochemistry. The mRNA and protein expression of OPN and TGF-beta1 was
      detected by real-time quantitative reverse transcription-PCR and western
      blotting, respectively. Significance of differences between multiple groups was
      assessed by one-way ANOVA analysis followed by least significant difference t
      test or Kruskal-Wallis H test followed by the Mann-Whitney U test. RESULTS:
      Compared to the control groups, the group of mice administrated ethanol and CCl4
      developed mild to moderate hepatic steatosis at week 4 of modeling, progressive
      necroinflammation and perisinusoidal and portal fibrosis from weeks 5-8, and
      irregular necrosis and bridging fibrosis at week 8. In addition, the model group
      showed progressive up-regulation of a-SMA expression in the activated hepatic
      stellate cells (HSCs) and fibrotic areas from weeks 5-8. Both hepatic OPN and TGF
      beta1 showed significantly increasing trends in mRNA and protein expressions from
      weeks 5-8 (OPN mRNA: 1.83 +/- 0.25, 2.94 +/- 0.19, 3.45 +/- 0.31, and 5.99 +/-
      0.17 (F= 476.27, P < 0.001); OPN protein: 0.52 +/- 0.06, 1.02 +/- 0.10, 1.52 +/-
      0.11 and 1.50 +/- 0.08 (F= 298.03, P< 0.001); TGF-beta1 mRNA: 13.19 +/- 0.40,
      3.31 +/- 0.28, 1.58 +/- 0.18 and 2.08 +/- 0.26 (F= 85.55, P < 0.001); TGF-P31
      protein: 1.26 +/- 0.16, 0.96 +/- 0.12, 1.09 +/- 0.25 and 1.10 +/- 0.20 (F =
      43.64, P < 0.001). CONCLUSION: Feeding C57BL/6J mice the Lieber-DeCarli ethanol
      containing liquid diet combined with CCl4 intraperitoneal injection is a
      convenient method to establish a model of alcoholic liver fibrosis within a
      relatively short amount of time (eight weeks). Progression of alcoholic liver
      fibrosis is accompanied by increased hepatic expression of OPN and TGF-beta1,
      which may contribute to the pathogenic mechanism of this disease and may be
      targets of future molecular therapies.

PMID- 23967744
TI  - [ShRNA-mediated silencing of MDM2 inhibits growth of HepG2 hepatocellular
      carcinoma cells xenografted in nude mice].
AB  - OBJECTIVE: To construct a short hairpin (sh)RNA targeting the gene encoding the
      MDM2 oncoprotein in order to investigate its role in human hepatocellular
      carcinoma (HCC) and its potential for use as a gene therapy strategy to inhibit
      HCC growth in vivo. METHODS: Small interfering (si)RNAs were designed targeting
      the MDM2 gene (siMDM2-1 and siMDM2-2) and unrelated sequences (negative control)
      and cloned into the expression plasmid pGCSilencer-U6-neo-GFP. A HCC mouse model
      was established by subcutaneous inoculation of HepG2 cells (2 x 10(6) in 0.2 ml)
      into 20 nude mice. The inoculated mice were divided into four equal groups for
      tumor-localized injections of saline, negative control siRNA plasmid, siMDM2-1
      plasmid, and siMDM2-2 plasmid. Tumor growth was observed daily (by caliper
      measurement) for one month, when mice were sacrificed by cervical dislocation.
      The tumor mass was resected for analysis of tumor inhibition rate (% = [(average
      tumor weight of control group - average tumor weight of treatment group) /
      average tumor weight of control group x 100]) and effects on MDM2 and p53 mRNA
      and protein expression (by reverse transcription- PCR and western blotting, both
      normalized to beta-actin). Significance of between-group differences was assessed
      by one-way ANOVA or LSD test; pairwise comparisons were made by the Chi-squared
      test. RESULTS: siMDM2-1 and siMDM2-2 suppressed the xenografted tumor growth
      remarkably (60.6% and 54.6% inhibition rates, respectively), significantly
      reduced the expression ofMDM2 gene (62.8% and 61.6%) and protein (60.7% and
      59.5%), and significantly increased p53 gene (47.1% and 45.6%) and protein (45.9%
      and 44.3%) (all, P < 0.05). CONCLUSION: shRNA-mediated silencing of the MDM2 gene
      effectively inhibits HCC tumorigenesis of subcutaneously xenografted HepG2 cells
      in nude mice, and the mechanism may involve p53.

PMID- 23967745
TI  - [Effects of PPAR-alpha activation on oleic acid-induced steatosis and expression
      of heme oxygenase-1 in HepG2 cells].
AB  - OBJECTIVE: To investigate the effects of peroxisome proliferator activated
      receptor-alpha (PPAR-a) activation on oleic acid (OA)-induced steatosis and
      hepatic expression of heme oxygenase-1 (HO-1) using an in vitro cell model
      system. METHODS: A steatosis human hepatocyte in vitro model system was
      established by treating HepG2 cells with 0.2 mmol/L of oleic acid for 24 hours.
      The steatosis cells were then divided into four groups for an additional 24 hours
      of treatment with 0.2 mmol/L of oleic acid alone (model control group) or with 5,
      10 or 50 pnol/L of fenofibrate (FF, a selective PPAR-a agonist; experimental
      groups). Untreated HepG2 cells served as non-steatosis controls. Effect of PPAR-a
      activation on fat accumulation was detected by Oil Red O staining and on
      intracellular triglyceride (TG) levels by enzymatic assay. mRNA and protein
      expression of PPAR-alpha and HO-1 were quantified by real-time PCR and
      immunocytochemistry, respectively. One-way ANOVA and the LSD t-test were used for
      between-group comparisons, and correlation analysis was performed with the
      Pearson's correlation coefficient. RESULTS: The steatosis model control cells
      showed significantly increased TG deposition (379.98 +/- 23.19 mg/g protein, vs.
      non-steatosis controls F = 148.56, P< 0.01), significantly decreased mRNA and
      protein expression of PPAR-alpha (0.42 +/- 0.38,F= 177.64,P< 0.01 and 0.47 +/-
      0.14, F= 120.76,P< 0.01) and HO-1 (0.36 +/- 0.66, F= 74.77,P< 0.01 and 0.26 +/-
      0.10,F= 119.90,P<0.01). FF (5, 10 and 50 micromol/L) inhibited the steatosis
      induced by OA in a concentration-dependent manner (294.00 +/- 19.80, 250.33 +/-
      9.96, and 196.99 +/- 9.14, F = 148.56, P <0.01) and increased the mRNA and
      protein expression of PPAR-alpha (0.55 +/- 0.65, 0.85 +/- 0.61, and 1.31 +/-
      0.36,F= 177.64,P< 0.01; 0.82 + 0.11, 1.31 +/- 0.16, and 1.75 +/- 0.13, F=
      120.76,P <0.01) and HO-1 (0.62 +/- 0.05, 0.84 +/- 0.07, and 1.30 +/- 0.11,F=
      74.77,P <0.01; 0.44 +/- 0.08, 0.81 +/- 0.08, 1.20 +/- 0.10,F= 119.90,P< 0.01).
      CONCLUSION: Activation of PPAR-a prevents OA-induced steatosis in HepG2 cells,
      and HO-1 may function as a downstream effector of this mechanism.

PMID- 23967746
TI  - [Construction of short hairpin RNA targeting aquaglyceroporin 9 and screening its
      effect on molecular mechanisms of nonalcoholic fatty liver disease using a cell
      model system].
AB  - OBJECTIVE: To construct a short hairpin (sh)RNA targeting aquaglyceroporin 9
      (AQP9) that effectively silences gene expression in liver cells in order to
      investigate of the role of AQP9 in nonalcoholic fatty liver disease (NAFLD)
      pathogenesis using an in vitro cell model system. METHODS: Small interfering
      (si)RNAs were designed against the human gene sequences encoding AQP9 (NCBI
      GenBank Accession No. AB008775) and unrelated control sequences, synthesized,
      annealed to form double-strands, and inserted into the pGenesil- 1 shRNA
      expression plasmid. The silencing effects of the four pshRNA-AQP9 constructs (a
      d) and the pshRNA-negative control construct were investigated by transfecting
      into the L02 human normal liver cell line and detecting expression of AQP9 mRNA
      and protein (relative to beta-actin) by reverse transcription-PCR and western
      blotting. The NAFLD cell model was established by treating L02 cells with oleic
      acid to induce fatty degeneration. After transfecting the NAFLD cell model with
      various constructs, the effects on NAFLD-related features were investigated by
      staining with Oil Red O (to detect lipid droplets) and performing enzymatic
      assays (to quantitate triglyceride (TG), free fatty acid (FFA) and glycerol
      content). The significance of intergroup differences was assessed by analysis of
      variance test. RESULTS: Of the four pshRNA-AQP9 constructs, pshRNA-AQP9a produced
      the most robust silencing effect on AQP9 mRNA (25.1 - 1.2% vs. untransfected:
      39.3 +/- 1.7% and pshRNA-negative control: 39.4 +/- 1.5%, P < 0.01) and protein
      (25.4 - 2.0% vs. untransfected: 35.1 +/- 1.9% and psh-RNA-negative control: 35.6
      +/- 2.3%, P < 0.01). Oleic acid-induced L02 cells showed enhanced AQP9 mRNA and
      protein expression, and increased intracellular content of lipid, TG, FFA, and
      glycerol, which were significantly reduced by pshRNA-AQP9a transfection (all P
      <0.05). CONCLUSION: The new pshRNA-AQP9a construct can efficiently reduce AQP9
      expression in cultured human liver cells and relieve steatosis-related features
      in an NAFLD cell model, pshRNA-AQP9a represents a novel tool for studying the
      role ofAQP9 in NAFLD pathogenesis and its potential as a gene therapy strategy.

PMID- 23967747
TI  - [Echinococcus multilocularis infection leads to increased expression of
      proliferation and anti-apoptosis factors in liver cells in BALB/c mice].
AB  - OBJECTIVE: To investigate the effects of Echinococcus multilocularis on host
      liver cell proliferation in vivo using a BALB/c mouse alveolar hydatid infection
      model. METHODS: Sixty-five 8-10-week-old female BALB/c mice were randomly divided
      into an experimental group (n = 40) and a control group (n = 25) and administered
      an abdominal injection into the left liver lobe of E. multilocularis
      protoscolices in saline solution or saline solution alone, respectively. At post
      injection day 2, 8, 30, 60, and 90, liver samples were collected for analysis of
      lesions and lesion-adjacent tissue by hematoxylin-eosin staining and differential
      expression of proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin A, and
      cyclin B1 by immunohistochemical staining. The significance of intergroup
      differences was assessed by Student's t-test. RESULTS: The control group showed
      normal liver histology at all time points. The experimental group developed E.
      multilocularis lesions that showed increased severity of pathological features,
      such as inflammatory cell invasion, steatosis and fibrous connective tissue
      hyperplasia, over time. At post-injection days 2 and 8, enlarged, binuclear and
      apocyte hepatocytes were observed close to the lesions. At post-injection days
      30, 60, and 90, the number of hepatocytes expressing PCNA progressively increased
      in the experimental group, and the numbers were significantly higher than in the
      control group (7.01 +/- 1.89 vs. 1.03 +/- 0.52, 8.41 +/- 2.80 vs. 0.93 +/- 0.31,
      and 13.4 +/- 4.43 vs. 1.07 +/- 0.94; all P < 0.05). The same progressively
      increasing trend was seen in the number of hepatocytes expressing CyclinD1, but
      was only significantly different from controls at post-injection days 30 and 60
      (6.73 +/- 2.52 vs. 0.48 +/- 0.43 and 8.22 +/- 3.09 vs. 0.55 +/- 0.34; both P <
      0.05). In contrast, the number of hepatocytes expressing cyclin A was
      significantly increased at post-injection day 30 and then showed a decreasing
      trend at days 60 and 90, although the numbers of expressing cells remained
      significantly higher than control levels at all time points (7.75 +/- 3.05 vs.
      0.69 +/- 0.36, 3.42 +/- 1.80 vs. 1.14 +/- 0.42, and 3.03 +/- 1.50 vs. 0.69 +/-
      0.31; all P < 0.05). The number of hepatocytes expressing CyclinB1 in the
      experimental group was less robust than the other cyclins (with a general
      temporal trend of increase followed by decrease), but the differential expression
      was not significantly different from the control levels at any time point.
      CONCLUSION: E. multilocularis infection may promote the expression of host
      factors related to proliferation and anti-apoptosis in liver. This pathogen
      mediated modulation of host cell-survival mechanisms may provide a rationale
      explanation for the clinical observations of hepatomegaly and the unexpected
      survival of alveolar echinococcosis patients following major hepatic resection.

PMID- 23967748
TI  - [Clinical observation of YMDD mutation in HBV-related primary liver cancer with
      lamivudine].

PMID- 23967749
TI  - [Construction of lentivirus vectors containing PNPLA3 gene and overexpression of
      PNPLA3 in Huh-7 cells].

PMID- 23967750
TI  - [The observation of blood serum creatinine and phosphorus during long-term
      adefovir dipivoxil treatment in chronic hepatitis].

PMID- 23967751
TI  - Treatment of recalcitrant chronic urticaria with nonsedating antihistamines: is
      there evidence for updosing?
AB  - Nonsedating antihistamines are the first-choice treatment for all forms of
      urticaria. In patients with recalcitrant urticaria who do not respond to
      conventional doses of antihistamines, current guidelines recommend increasing
      doses by up to 4 times in order to obtain better control of the disease. Although
      few studies have been conducted, there are convincing data from controlled trials
      for cetirizine, levocetirizine, and desloratadine that support the use of
      increased doses of such drugs in unresponsive patients. The use of higher doses
      of antihistamines has not been associated with increased adverse effects or
      somnolence. More studies with other second-generation antihistamines are required
      in order to improve the treatment of patients with severe, recalcitrant
      urticaria.

PMID- 23967752
TI  - Prevalence of asthma and severity of allergic rhinitis comparing 2 perennial
      allergens: house dust mites and Parietaria judaica pollen.
AB  - BACKGROUND: Allergic rhinitis (AR) is an increasingly prevalent worldwide disease
      that has a considerable impact on quality of life and health care costs. Asthma
      and AR may be part of the same disease, with AR leading to an increased risk of
      asthma. OBJECTIVES: To assess the prevalence of asthma in patients with AR due to
      house dust mites (HDMs) or Parietaria judaica and analyze the characteristics of
      asthma and AR in each group. METHODS: Cross-sectional, multicenter study with
      recording of demographic and clinical characteristics. All patients had AR
      confirmed by symptoms and a positive skin prick test to HDMs or P judaica. They
      were classified according to the severity and frequency ofAR following the
      Allergic Rhinitis and its Impact on Asthma (ARIA) and modified ARIA criteria and
      according to the severity of asthma following the Global Initiative for Asthma
      criteria. RESULTS: We studied 395 patients (226 in the HDM group and 169 in the
      Pjudaica group) with a mean (SD) age of 43 (15.3) years. Using the modified ARIA
      criteria, we detected more severe and persistent AR in the P judaica group than
      in the HDM group (44.5% vs 24.8%, P < .001). Nevertheless, there were no
      statistically significant differences between the groups in terms of the severity
      or prevalence (50% in HDM vs 47.9% in P judaica, P = .685) of asthma. CONCLUSION:
      AR due to P judaica pollen, which behaves like a perennial allergen, is
      associated with the same prevalence of asthma and with more severe rhinitis than
      AR due to HDMs.

PMID- 23967753
TI  - Soy aeroallergens in thoracic fraction particles (PM10).
AB  - BACKGROUND: The aerodynamic diameter of biological particles determines their
      ability to penetrate the human respiratory system. OBJECTIVE: To assess the
      content of allergens less than 10 pm in diameter in the particle fraction of
      airborne dust in order to improve control of exposure to harmful soybean
      aeroallergens. METHODS: In this study, 98 pairs of particulate matter measuring
      less than 10 microm in diameter (PM10) and total suspended particulate (TSP)
      filters were collected in parallel and analyzed for soy aeroallergens by the
      inhibition enzyme-linked immunosorbent assay. RESULTS: The median levels found
      were 6 and 22.5 U/m3 for PM10 and TSP filters, respectively. A good correlation
      was found between soy aeroallergen content in PM10 and TSP filters. The median
      proportion of soy aeroallergen content in PM10 filters versusTSP filters was
      28.6%, and varied widely across different days. CONCLUSIONS: Due to this wide
      variation between days, it seems that soy aeroallergen content in TSP filters is
      not a good surrogate of soy allergen content in PM10 filters. Further clinical
      studies should be conducted to assess differences in the health impact of soy
      allergen content in PM10 filters and TSP filters.

PMID- 23967754
TI  - Identification of new potential allergens from Nile perch (Lates niloticus) and
      cod (Gadus morhua).
AB  - BACKGROUND: Globalization of the food industry has led to widespread exposure to
      new nondomestic fish species; therefore, identification of potential allergens is
      necessary in order to diagnose allergic reactions. OBJECTIVE: Contact with a
      patient who was allergic to Nile perch (Lates niloticus) prompted us to
      investigate the immunoglobulin (Ig) E-reactive proteins that could be allergens
      of this species. METHODS: 2D gel electrophoresis was used to separate the muscle
      proteins of L niloticus and Gadus morhua. Immunoblotting was performed with sera
      from 12 patients with a history of immediate-type allergic reaction to fish and
      from atopic and nonatopic controls. IgE-reactive proteins were detected and
      identified using mass spectrometry. RESULTS: The index patient had low levels of
      IgE binding to parvalbumins. However, 8 putative allergens other than parvalbumin
      from L niloticus and 5 from G morhua were identified. Further investigation
      revealed cross-sensitivity to enolase 3 from L niloticus in 7 of the 12 fish
      allergic individuals (58%), whereas 11 of the 12 patients (92%) were sensitized
      to enolase 3 from G morhua. However, atopic control patients were also sensitized
      to enolase 3 from L niloticus and G morhua. CONCLUSION: Identification of species
      specific allergens and individual sensitization could help us to improve
      avoidance strategies.

PMID- 23967755
TI  - Immunoglobulin E reactivity and allergenic potency of Morus papyrifera (paper
      mulberry) pollen.
AB  - BACKGROUND: Paper mulberry (Morus papyrifera) pollen is considered to be one of
      the most clinically relevant aeroallergens in Pakistan. To date, the
      allergenicity of the pollen has not been investigated. OBJECTIVE: To characterize
      the sensitization profile of mulberry-allergic patients and the proteins of paper
      mulberry pollen contributing to pollinosis in the Pakistani population. METHODS:
      Proteins were extracted from mulberry pollen using different protocols.
      Immunoglobulin (Ig) E binding proteins to mulberry pollen was determined by
      ImmunoCAP testing and immunoblotting using sera from 29 mulberry pollen-allergic
      patients with positive skin prick test results to mulberry pollen antigens. The
      histamine release assay was performed in vitro to determine the allergenic
      potency of pollen extracts and a partially purified mulberry pollen allergen. The
      protein was identified using N-terminal sequencing and matrix-assisted laser
      desorption/ionization-time of flight spectrometry (MALDI-TOF/TOF). RESULTS: IgE
      sensitization to mulberry pollen was confirmed by positive ImmunoCAP results to
      pollen from Morus alba (white mulberry) in 23 out of 29 mulberry pollen-allergic
      patients. A 10-kDa protein from the paper mulberry pollen extract was considered
      a major allergen, along with additional IgE-reactive proteins. Sera from 79% of
      the patients reacted to the 10-kDa allergen, which showed substantial capacity to
      trigger histamine release in 3 out of 4 patients. N-terminal sequencing and MALDI
      TOF/TOF yielded an amino acid sequence with no homology to known proteins.
      CONCLUSIONS: Mulberry-allergic patients are sensitized to multiple mulberry
      pollen allergens. We identified a novel 10-kDa protein that was a major allergen
      and should be further investigated for diagnostic and therapeutic purposes.

PMID- 23967756
TI  - Allergen profile of Protophormia terraenovae, other species of calliphoridae, and
      Lumbricus terrestris in anglers allergic to maggots in Caceres, Spain.
AB  - BACKGROUND: Our group previously found that up to 7% of amateur anglers in
      Caceres, Spain may be allergic to the larvae of Protophormia terraenovae (order
      Diptera, family Calliphoridae) used as live bait for fishing. OBJECTIVE: To
      identify the pattern of major allergens in P terraenovae and other species of
      Calliphoridae. MATERIALS AND METHODS: Extracts of P terraenovae, Calliphora
      vomitoria, Lucilia sericata and Lumbricus terrestris were characterized using
      sodium dodecyl sulfate polyacrylamide gel electrophoresis and IgE-immunoblotting
      techniques in individual sera from 24 patients with a positive skin test result
      and/or specific IgE determination (enzyme-linked immunosorbent assay [ELISA]) to
      P terraenovae. ELISA and IgE-immunoblotting inhibition studies were also
      performed to identify potential cross-reactive allergens between these species.
      RESULTS: IgE-immunoblotting with P terraenovae showed a band of 15.3 kDa
      recognized by 15 patients, in addition to 2 further allergens of 22.8 kDa and 69
      kDa. For C vomitoria, 5 bands of 73, 46, 40, 28, and 14 kDa were observed. For L
      sericata, 2 major allergens of 73 kDa and 14 kDa were observed. In the case of L
      terrestris, IgE from 13 patients recognized 1 allergen of around 15.5 kDa. IgE
      immunoblotting and ELISA inhibition revealed the presence of cross-reactivity,
      mainly between L terrestris and P terraenovae. CONCLUSIONS: P terraenovae appears
      to have species-specific allergens and allergens shared with C vomitoria and L
      sericata. Striking immunological cross-reactivity was observed between P
      terraenovae and L terrestris. An allergen of 15-16 kDa could be involved in this
      phenomenon.

PMID- 23967757
TI  - Skin test-positive immediate hypersensitivity reaction to iodinated contrast
      media: the role of controlled challenge testing.
AB  - BACKGROUND: Immediate hypersensitivity reactions (IHR) to iodinated contrast
      media (ICM) have traditionally been considered nonallergic; however, the
      increasingly frequent reporting of positive skin test and basophil activation
      test results suggests a specific allergic mechanism in some patients. Skin tests
      have been proposed as a useful tool for diagnosis, although their sensitivity and
      predictive values remain to be determined. The role of controlled challenge
      testing has not been assessed. OBJECTIVE: We aimed to evaluate the role of
      controlled challenge testing in skin test-positive IHR to ICM. PATIENTS AND
      METHODS: We evaluated 106 patients with IHR to ICM by performing skin tests with
      the agent that caused the reaction. Patients with a positive result were
      selected. Skin tests were extended to a series of 8 ICMs; 5 patients underwent
      controlled challenge test with an alternative skin test-negative ICM; a further 2
      patients underwent computed tomography with an alternative skin test-negative
      ICM. No premedication was administered. RESULTS: Intradermal test results were
      positive to the ICM that caused the reaction in 11 out of 106 patients (10.4%).
      Five of the 11 patients tolerated a controlled challenge test with an alternative
      skin test-negative ICM. The 2 patients who underwent computed tomography with an
      alternative skin test-negative ICM tolerated the medium. CONCLUSIONS: Skin tests
      are useful for the diagnostic workup in patients with an allergic IHR to ICM.
      Since ICM cannot be avoided in many patients because they are irreplaceable in
      some diagnostic or therapeutic techniques, an alternative safe ICM should be
      investigated for future procedures. We propose the use of controlled challenge
      tests based on skin test results to address this need in skin test-positive
      reactions in order to identify an alternative non-cross-reactive ICM.

PMID- 23967758
TI  - Sequential combined therapy with omalizumab and rituximab: a new approach to
      severe atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disease, and a
      significant percentage of AD patients have severe forms. Inflammation based on
      type 2 helper T cells (T(H)2), autoantibodies, and CD8+ T cells could play a
      relevant role in this disease. When the patient requires systemic
      immunosuppressors for disease control, side effects are frequent. We propose a
      sequential therapeutic strategy with 2 monoclonal antibodies, omalizumab (anti
      immunoglobulin [Ig] E) and rituximab (anti-CD20), which might induce clinical
      benefit with few side effects in selected individuals with AD. METHODS: We report
      6 cases of severe AD refractory to conventional therapy. The patients underwent
      sequential switch therapy with omalizumab and rituximab. Clinical response was
      assessed by means of the decrease in body surface affected. Immunological
      parameters and side effects were also monitored. RESULTS: Four patients received
      omalizumab before a high-dose cycle of rituximab. In the case of recurrences,
      either low-dose cycles of rituximab or omalizumab were administered. A long-term
      clinical benefit was observed in 3 out of 4 patients. Two patients first received
      high-dose rituximab followed by either low-dose rituximab or omalizumab, and one
      of them achieved a response at 17 months. No severe side effects were recorded.
      Serum IgE level and B-cell counts decreased with therapy, the latter returning to
      baseline levels 10 to 11 months after treatment. Specific antibody responses
      remained protective during the study. CONCLUSIONS: With our proposed switch
      therapy, 4 out of 6 patients achieved a dramatic clinical improvement. This novel
      strategy targets different arms of the immune response and might be a good
      alternative for patients with severe AD.

PMID- 23967759
TI  - Pollen-food syndrome involving allergy to tiger nut.

PMID- 23967760
TI  - Echinococcus multilocularis infection in a patient treated with omalizumab.

PMID- 23967761
TI  - Safety of 2 build-up cluster immunotherapy schedules with a high-dose
      hypoallergenic pollen therapeutic extract.

PMID- 23967762
TI  - Cardiorespiratory arrest: a grade IV delayed anaphylactic reaction in the
      recovery room caused by rocuronium.

PMID- 23967763
TI  - Urticaria caused by ingestion of pasta and bread containing buckwheat flour.

PMID- 23967764
TI  - Chronic urticaria caused by allergy to peach lipid transfer protein.

PMID- 23967765
TI  - High prevalence of allergy-like respiratory diseases in common variable
      immunodeficiency.

PMID- 23967766
TI  - Nonhistaminergic idiopathic angioedema may be a presentation of mast cell
      activation syndrome.

PMID- 23967767
TI  - The effectiveness of a phonics-based early intervention for deaf and hard of
      hearing preschool children and its possible impact on reading skills in
      elementary school: a case study.
AB  - The study explored the effects of a phonics-based early intervention package on
      the early reading skills of three preschool students who were d/Deaf or hard of
      hearing who differed in regard to degree of hearing loss, use of amplification,
      and communication mode. The 40-week intervention (50-week in one case) was
      delivered through individual and group phonics-based instruction supplemented by
      Visual Phonics in a language-enriched preschool classroom. Standardized
      assessments were conducted before, during, and after the intervention. Along with
      some additional assessments, the same assessments were conducted in early
      elementary school. The results showed that all participants demonstrated at least
      some use of phonemic awareness and phonics skills when they were explicitly
      trained, and that these skills were sustained in early elementary school.
      Furthermore, all participants exhibited overall reading levels at or above age
      level when measured in early elementary school.

PMID- 23967768
TI  - Lessons from the final report of the Francis inquiry.

PMID- 23967769
TI  - How can we monitor palliative care? Suggestions from the Latin American
      Association for Palliative Care.

PMID- 23967770
TI  - End-of-life care in neurodegenerative conditions: outcomes of a specialist
      palliative neurology service.
AB  - BACKGROUND: People with advanced neurological conditions (ANCs) face complex
      problems and needs that are often unrecognised and undertreated.Their last year
      of life may be characterised by unplanned hospital admissions and an unexpected
      death. A National End-of-Life Care Programme (NEoLCP) 2010 framework made
      recommendations to aid timely and appropriate end-of-life care for people with
      ANCs. OBJECTIVES: Assessment of key outcomes of a UK nurse-led palliative
      neurology service against the NEoLCP standards. METHOD: A retrospective study of
      clinical records of patients who died from an ANC under the care of the service
      from December 2006 to April 2012. RESULTS: All 62 patients had multidisciplinary
      care coordinated by a key worker-a clinical nurse specialist (CNS) in palliative
      neurology. Mental capacity was assessed in 95% of cases, of which 95% had a
      documented advance care plan or best interest decision.The CNS had specific input
      regarding carer distress in 77% of cases. Mean hospital admissions were 0.9 per
      patient in the last year of life, compared with 3.5 nationally across all
      diagnoses. The service demonstrated better outcomes in other key areas, including
      place of death, with more patients dying at home or in the hospice compared with
      national figures. CONCLUSION: This service model fulfils key NEoLCP
      recommendations, as well as resulting in low hospital admissions and deaths.

PMID- 23967771
TI  - The experiences of patients undergoing blood transfusion in a day hospice.
AB  - AIM: To explore patients' views on living with anaemia and undergoing blood
      transfusions in a day hospice. METHODS: This was a qualitative study using semi
      structured interviews. Ten patients who between them had received 90 transfusions
      were purposively sampled from the hospice day unit. The interviews were
      digitially recorded, transcribed anonymously, and the transcripts analysed using
      a phenomenological analysis framework. FINDINGS: Tiredness was the most common
      symptom of anaemia. Participants liked attending the day hospice instead of
      hospital for their transfusions owing to differences in transport, parking,
      waiting time, and space to ask questions. The majority had no concerns about
      hospice transfusion and would be happy to return for further treatment.
      CONCLUSIONS: Haematology patients can have a good experience when undergoing
      blood transfusion at a day hospice. Hospices should perhaps offer this procedure
      more widely.

PMID- 23967772
TI  - New Zealand hospice nurses' self-rated comfort in conducting spiritual
      assessment.
AB  - AIM: To measure how comfortable hospice nurses in New Zealand are in conducting
      spiritual assessment and explore potentially associated factors. DESIGN: Cross
      sectional, mixed-methods, descriptive study. SAMPLE AND SETTING: Sixty hospice
      nurses from three New Zealand hospices. METHODS: An investigator-designed
      questionnaire measured respondents' comfort with asking patients spiritual
      assessment questions proposed for use in the health-care literature. Other items
      assessed personal and work-related factors. Open questions generated data about
      how these nurses assess spirituality.The data was analysed using measures of
      central tendency, binomial non-parametric tests, and content analysis. FINDINGS:
      These nurses were generally comfortable with proposed spiritual assessment
      questions and perceived spiritual assessment to be important. Personal factors
      including age, years in nursing, religiosity, and spirituality were not related
      to this comfort; however, training was associated with comfort. CONCLUSION: These
      findings underscore the importance of training and show how nurses can be
      comfortable with and capable of assessing patient spirituality.

PMID- 23967773
TI  - Euthanasia: the perceptions of nurses in India.
AB  - Euthanasia provokes controversies in various domains, such as the moral, ethical,
      legal, religious, scientific, and economic. India legalised passive euthanasia
      (withdrawal of life support) for patients with brain death or who are in a
      permanent vegetative state in 2011, but research on perceptions of euthanasia
      among people in India is limited. This study aimed to examine nurses' perceptions
      of the practice of euthanasia as well as factors influencing those perceptions. A
      non-probability quantitative, cross-sectional design was adopted for a sample of
      214 nurses working at a tertiary care centre. Data was collected through self
      reported questionnaires at the nurses workplace.The findings revealed mixed
      opinions on euthanasia among the nurses. However, the majority of the
      participants did not agree with the practice of euthanasia. Nonetheless, further
      research is needed on this issue across the country among various health
      professionals in the context of current legislation.

PMID- 23967774
TI  - Home visiting nurses' attitudes toward caring for dying patients, and related
      workplace factors.
AB  - AIM: To identify workplace factors related to home visiting nurses (HVNs)
      positive attitudes toward caring for dying patients. METHODS: In this cross
      sectional study, 343 HVNs working in 62 agencies across Chiba prefecture, eastern
      Japan, received an anonymous self-administered questionnaire from July to August
      2012. RESULTS: 304 questionnaires (88.6%) were returned, and the data of 206 HVNs
      (60.1%) in 54 different agencies was analysed. Multiple regression analysis
      showed that attendance at terminal care seminars, agency support of schedule
      organisation enabling attendance at terminal care seminars, and positive feedback
      from patients and families were significantly positively associated with HVNs'
      attitudes toward terminal care. CONCLUSION: These results may give useful
      interventional methods for nursing managers to enhance HVNs terminal care
      practices.

PMID- 23967775
TI  - Ten commandments of EMS leadership.

PMID- 23967776
TI  - Reel lessons.

PMID- 23967777
TI  - PEAT.

PMID- 23967778
TI  - Vegas stings.
AB  - The case detailed here is relatively straight-forward. We describe the case of a
      tourist who sustained a scorpion sting in a local state park. Her symptoms were
      more significant than typically seen with simple scorpion stings. The scorpion
      that was caught by her boyfriend was later determined to be a bark scorpion.
      However, following adequate prehospital treatment and detailed evaluation in the
      emergency department, the patient improved. It was determined that scorpion
      antivenin wasn't indicated bacause of the lack of systemic signs and symptoms.
      The patient ultimately did well and completed her vacation in Las Vegas.

PMID- 23967780
TI  - Safety & the future.

PMID- 23967779
TI  - The triple aim.

PMID- 23967781
TI  - Add a little salt.

PMID- 23967782
TI  - EMS at the healthcare table.

PMID- 23967783
TI  - Cerebral recovery.

PMID- 23967784
TI  - Provider to patient.

PMID- 23967785
TI  - TXA: a difference-maker for trauma patients.

PMID- 23967786
TI  - Germ warfare.

PMID- 23967787
TI  - Emergency management of dyspnea in dying patients.
AB  - Many terminally ill patients seek care in the emergency department. Understanding
      how to elicit goals of care from dying patients and initiate basic palliative
      measures is well within the scope of emergency medicine. While a wide variety of
      factors drive patients at the end of life into the acute-care setting, dyspnea is
      one of the most distressing symptoms experienced by dying patients, and it is a
      common reason for such patients to seek care. Many underlying disease states and
      acute illnesses account for shortness of breath at the end of life, and
      management tends to be symptomatic rather than diagnostic, particularly in those
      for whom comfort is the most important goal. Opioids are the most effective and
      widely studied agents available for palliation of dyspnea in this population,
      while adjuvant therapies such as oxygen, noninvasive positive pressure
      ventilation, and fans may also play a role. Other medications (eg,
      benzodiazepines and low-dose ketamine) may also be useful in select patients. The
      early involvement of palliative medicine specialists and/or hospice services for
      dying patients can facilitate optimal symptom management and transitions of care.

PMID- 23967788
TI  - Bioethics.

PMID- 23967789
TI  - Assessing clinical ethics consultation: processes and outcomes.
AB  - The vast majority of hospitals use clinical ethics consultation (CEC) as a
      service to address ethical issues in patient care. Both proponents and critics
      alike recognize a need to evaluate CEC. I review three outcomes of CEC that have
      been formally evaluated: healthcare cost, clinical indicators in the intensive
      care unit, and user satisfaction. These outcome indicators cannot be used to
      evaluate the worth of CEC because they are contingent and outside of the
      consultant's control. However, the failure of outcomes-based assessment poses no
      threat to CEC since the service is continually justified by the fundamental
      necessity of resolving ethical problems in patient care. While outcome indicators
      can be used as heuristics to investigate quality issues in CEC, process
      indicators can capture the quality of CEC more directly. Therefore, further
      research should be directed toward developing process-based conceptual models for
      CEC and various methods for assessing these processes.

PMID- 23967790
TI  - The art of 'autonomy': on the use and usefulness of the term in clinical
      bioethics.
AB  - Autonomy is highly regarded in American bioethics. Its prevalence in the
      literature might lead one to believe that the term's meaning is well established,
      but, as the article argues, it is unlikely that this is the case. The term
      autonomy is used to denote a complex of related ideas, and speakers have in mind
      one or more of these ideas when they employ the term. However, speakers rarely
      make explicit exactly which ideas or notions of autonomy they intend when using
      the term in clinical discussions of patient autonomy. This frequent omission
      prompts the central question of the article: Does employing the term autonomy
      with its many meanings help or hinder clinical discussions of whether patients
      and their choices ought to be respected? Does use of the term autonomy in the
      clinical setting clarify or confound? The article concludes that the prominence
      of autonomy may belie its problems.

PMID- 23967791
TI  - Why bioethics? On the anamnesis of meaning in medicine.
AB  - The history of bioethics rests upon the assumption that, given the growing
      complexity of medicine, the function of ethics is, first of all, normative:
      ethics is supposed to help in the solution of concrete problems, and to do so
      systematically, by relying upon a defined set of principles and rules. The
      scientific character of such an approach to bioethics complements the very
      understanding of modern medicine as itself increasingly scientific and technical,
      that is, as oriented toward the production of effects. Although careful
      scientific attention to the patho-physiology of disease has unquestionably
      yielded marvelous advances in modern medicine, its positivist reduction has also
      created a mind-set that brackets questions of meaning, themselves highly
      significant to human well-being and to the ethical aspects ofmedicine. The paper
      claims that, rather than sharing in the "suspension of meaning" pursued by
      medicine for the sake of scientific objectivity, the main task of bioethics
      consists in a retrieval, or "anamnesis", of the very questions medicine seems to
      suspend: the significance of illness and disease, of birth, suffering and death,
      and of the service to the ethos of generosity that sustains the healing
      professions. Also, the paper offers a cultural "etiology" of "the suspension of
      meaning" in bioethics. In addition to a critical integration of positivistic
      attitudes in medicine and the reduction of moral discourse to the normative, one
      must mention the basic presumption of a cultural situation that, in the name of
      post-modernity, raises serious doubts against the possibility of engaging in
      questions of meaning across moral boundaries. As an alternative, the paper calls
      for a moral reflection that begins neither with the application of normative
      principles, nor with an attitude of resignation towards the pursuit of the good;
      rather with a free and open confrontation with clinical experience that attends
      to the moral meaning of concrete situations, recognizing that formal modes of
      logical argumentation are only derivative functions of the moral language, and,
      thus, cannot exhaust the broad spectrum of ethical discourse in bioethics.

PMID- 23967792
TI  - Social utility and pandemic influenza triage.
AB  - In a public health disaster, such as an influenza pandemic, the focus of medical
      care shifts from the needs of the individual to those of the community, so that
      the greatest good for the greatest number may be achieved. In a pandemic it will
      be necessary to maximize the benefit derived from all available local resources.
      Triage is the device employed to decide which patients will receive these limited
      medical resources. Current Pandemic Influenza triage protocols uniformly omit any
      consideration of individual social utility, value or worth. Yet, based upon the
      severity of a pandemic it may be necessary and justifiable to include these
      criteria in making allocation decisions. The extent and manner of inclusion will
      directly correlate with pandemic severity. This paper considers existing
      protocols and proposes a manner for fully realizing the goals applicable in a
      public health crisis.

PMID- 23967793
TI  - "Their numbers have been recorded": choiceless choice and the ethics of Sara
      Nomberg-Przytyk.
AB  - In this paper, I will examine several stories written by Holocaust survivor Sara
      Nomberg-Przytyk. Taken from her autobiographical collection, Auschwitz: True
      Tales from a Grotesque Land (1967),"The Price of Life", "The Dance of the
      Rabbis," and "The Verdict" are three of forty short narratives the Polish Jewish
      writer compiled as literary testimony of her experience. During her time in
      Auschwitz, Nomberg-Przytyk held the comparatively fortunate position of infirmary
      worker, a position she earned by her pre-War leadership in the underground Polish
      Communist party. In these stories and others in the collection, she examines the
      daily ethical dilemmas faced by those working on the front lines of the Auchswitz
      death-and duplicity machine. As witnesses, they saw death in all forms, including
      mass piles of corpses, and in places that were devised to be duplicitous, such as
      the infamous "showers" that were actually gas chambers. They felt death in the
      human ashes that rose up from the crematoria and floated over their bodies as
      they navigated through their days and nights in the camp. As a witness to this
      landscape of death, Sara Nomberg-Przytyk offers us an opportunity to examine the
      nearly impossible notion of choice and human dignity within the concentrationary
      universe of Auschwitz. Through these stories, Sara Nomberg-Przytyk teaches us
      about Jewish ethics in the face of Auschwitz.

PMID- 23967794
TI  - Bioethics consultation: the Rashomon effect.
AB  - Most clinical ethical dilemmas are resolved when the facts are clear,
      communicated to all involved, and the stakeholders agree on goals consistent with
      the patient's best interests and values. However, in some instances, participants
      continue to remember and observe the same situation differently, and resolution
      remains elusive. This article refers to the classic film, Rashomon, in which the
      truth remains different for four observers of the same scene. The discussion
      explores the phenomenon, provides some examples and recommendations for what
      remain very difficult ethical dilemmas.

PMID- 23967795
TI  - Medication regimes in the context of end-of-life decisions in neonatology: legal
      considerations with regard to Dutch NICU-practice.
AB  - Developments in legal and medical research concerning end-of-life decisions
      regarding severely suffering neonates in the Netherlands provide good cause for
      reflection on specific items of this issue. This article deals with the outcomes
      of the first national survey on end-of-life practice in Dutch Neonatal Intensive
      Care Units (NICUs) and examines the legal aspects of the use of medication as a
      part of this practice. The authors particularly reflect on the application of
      analgesics and sedatives on the one hand and neuromuscular blockers (NMBs) on the
      other hand. Furthermore, they focus on different elements of medicinal use such
      as indication, the moment of administering, dosage, effects of combinations of
      drugs, the relationship to the causation of death and (failures in)
      documentation.

PMID- 23967796
TI  - The detection of oral pre- malignant lesions with an autofluorescence based
      imaging system (VELscopeTM) - a single blinded clinical evaluation.
AB  - OBJECTIVE: The disease specific five-year survival rate especially for patients
      with advanced oral cancer has not improved significantly over the period of time.
      The most effective way of combating this dilemma is an early detection, diagnosis
      and eradication of early-stage lesions and their precursors. The use of
      VELscope(r) using an autofluorescence as a diagnostic tool might be useful in
      early detection of oral malignant lesions. MATERIALS AND METHODS: 120 patients
      with suspicious oral premalignant lesions were examined with two examination
      methods. They were randomly divided into two groups. Group 1 was examined
      conventional with white-light and group 2 was examined additionally to the white
      light-examination with an autofluorescence visualization device, VELscope(r).
      Biopsies were obtained from all suspicious areas identified in both examination
      groups (n = 52). The diagnostic strategies were compared regarding sensitivity
      and specificity. RESULTS: Based upon the result, use of the VELscope(r) leads to
      a higher sensitivity (22.0%), but regarding specificity the additional use of the
      VELscope(r) is inferior (8.4%). CONCLUSION: The VELscope device is a simple, non
      invasive test of the oral mucosa, which can help the experienced clinician to
      find oral precursor malignant lesions.

PMID- 23967797
TI  - Easy synthesis of high-purity BiFeO3 nanoparticles: new insights derived from the
      structural, optical, and magnetic characterization.
AB  - Synthesis of high-purity BiFeO3 is very important for practical applications.
      This task has been very challenging for the scientific community because
      nonstoichiometric Bi(x)Fe(y)O(z) species typically appear as byproducts in most
      of the synthesis routes. In the present work, we outline the synthesis of BiFeO3
      nanostructures by a combustion reaction, employing tartaric acid or glycine as
      promoter. When glycine is used, a porous BiFeO3 network composed of tightly
      assembled and sintered nanocrystallites is obtained. The origin of high purity
      BiFeO3 nanomaterial as well as the formation of other byproducts is explained on
      the basis of metal-ligand interactions. Structural, morphological, and optical
      analysis of the intermediate that preceded the formation of porous BiFeO3
      structures was accomplished. The thorough characterization of BiFeO3
      nanoparticles (NPs) included powder X-ray diffraction (XRD); scanning electron
      microscopy (SEM) and high resolution transmission electron microscopy (HRTEM);
      thermogravimetric analysis (TGA); UV-vis electronic absorption (diffuse
      reflectance mode), Raman scattering, Mossbauer, and electron paramagnetic
      resonance (EPR) spectroscopies; and vibrating sample magnetometry (VSM). The
      byproducts like beta-Bi2O3 and 5 nm Bi2Fe4O9 NPs were obtained when tartaric acid
      was the promoter. However, no such byproducts were formed using glycine in the
      synthesis process. The average sizes of the crystallites for BiFeO3 were 26 and
      23 nm, for tartaric acid and glycine promoters, respectively. Two band gap
      energies, 2.27 and 1.66 eV, were found for BiFeO3 synthesized with tartaric acid,
      obtained from Tauc's plots. A remarkable selective enhancement in the intensity
      of the BiFeO3 A1 mode, as a consequence of the resonance Raman effect, was
      observed and discussed for the first time in this work. For glycine-promoted
      BiFeO3 nanostructures, the measured magnetization (M) value at 20,000 Oe (0.64
      emu g(-1)) was ~5 times lower than that obtained using tartaric acid. The
      difference between the M values has been associated with the different
      morphologies of the BiFeO3 nanostructures.

PMID- 23967798
TI  - Natural orifice transluminal endoscopic surgery (NOTES) for clinical management
      of intra-abdominal diseases.
AB  - Clinical research on natural orifice transluminal endoscopic surgery (NOTES) has
      been increasingly reported over the past 5 years and more than 1200 patients have
      received various NOTES procedures. The present article reviews the clinical
      practice of NOTES for the treatment of intra-abdominal diseases, and was carried
      out through systematic search with specific keywords in major databases for NOTES
      related clinical literature. The last date of the search was 15 August, 2012.
      Transvaginal cholecystectomy is the commonest NOTES procedure reported, and its
      clinical feasibility and safety was established through prospective case series
      and randomized trials. There is a regional difference in NOTES development with
      the majority of NOTES fromCaucasian countries being transvaginal cholecystectomy
      and most reports from Asian countries being NOTES-related procedures. Safe
      closure of gastrointestinal access remains challenging, and novel endoscopic
      instruments are essential to enhance future development of NOTES. 

PMID- 23967800
TI  - Synthesis of polyfluoroalkyl cyclobutenes from 3-aza-1,5-enynes via an aza
      Claisen rearrangement/cyclization cascade.
AB  - A facile synthetic route to access polyfluoroalkyl functionalized cyclobutenes
      bearing an exo cyclic double bond from 3-aza-1,5-enynes is reported. The reaction
      proceeds via a thermal aza-Claisen rearrangement to give an allene-imine
      intermediate; subsequent cyclization affords the cyclobutene core. The kinetics
      of the transformation of starting material and the intermediate was studied by
      (1)H NMR spectroscopy, where a consecutive reaction was revealed. 

PMID- 23967799
TI  - Screen time use in children under 3 years old: a systematic review of correlates.
AB  - BACKGROUND: A large percentage (68%) of children under age 3 use screen media,
      such as television, DVDs and video games, on a daily basis. Research suggests
      that increased screen time in young children is linked to negative health
      outcomes, including increased BMI, decreased cognitive and language development
      and reduced academic success. Reviews on correlates of screen time for young
      children have included preschool age children and children up to age 7; however,
      none have focused specifically on correlates among infants and toddlers. As
      research suggests that screen media use increases with age, examining correlates
      of early media exposure is essential to reducing exposure later in life. Thus,
      this paper systemically reviews literature published between January 1999 and
      January 2013 on correlates of screen time among children between 0 and 36 months
      of age. METHODS: Two methods were used to conduct this review: (1) Computerized
      searches of databases (PubMed, PsycINFO, ERIC, Medline); and (2) Reference
      sections of existing reviews and primary studies. Inclusion criteria were: (1)
      The article included separate data for children 36 months and younger, (2)
      English language, (3) peer reviewed article, (4) analysis reported for screen
      viewing as a dependent variable, (5) original research article and, (6) examined
      correlates or associations between screen time and other demographic, contextual
      or behavioral variables. Articles were compiled between 2011 and 2013 and
      evaluation occurred in 2012 and 2013. RESULTS: The literature search identified
      29 studies that met inclusion criteria. These studies investigated a total of 33
      potential correlates, which were examined in this review. Findings suggest
      demographic variables most commonly correlated with high screen time among
      infants and toddlers are child's age (older) and race/ethnicity (minority). Child
      BMI, maternal distress/depression, television viewing time of the mother and
      cognitive stimulation in the home environment were also associated with screen
      media use. Studies reported that child sex, first born status, paternal
      education, non-English speaking family, two-parent household, number of children
      in the home and non-parental childcare were not associated with screen time among
      children aged 0-36 months. Associations were unclear (fewer than 60% of studies
      report an association) for maternal age, maternal education and household income.
      The remaining correlates were investigated in fewer than three studies and thus
      not coded for an association. CONCLUSIONS: The correlates identified in this
      study point to avenues for intervention to reduce screen time use in young
      children. However, further research is necessary to explore a number of
      environmental, socio-cultural and behavioral correlates that are under-examined
      in this population and may further inform prevention and intervention strategies.

PMID- 23967801
TI  - Brightly blue and green emitting Cu(I) dimers for singlet harvesting in OLEDs.
AB  - With the chelating aminophosphane ligands Ph2P-(o-C6H4)-N(CH3)2 (PNMe2) and Ph2P
      (o-C6H4)-NC4H8 (PNpy), the four halide (Cl, Br, I)-bridged copper coordination
      compounds [Cu(MU-Cl)(PNMe2)]2 (1), [Cu(MU-Br)(PNMe2)]2 (2), [Cu(MU-I)(PNMe2)]2
      (3), and [Cu(MU-I)(PNpy)]2 (4) were synthesized and structurally characterized.
      Their photophysical properties were studied in detail. The complexes exhibit
      strong blue (lambdamax = 464 (3) and 465 nm (4)) and green (lambdamax = 506 (1)
      and 490 nm (2)) luminescence as powders with quantum yields of up to 65% at decay
      times as short as 4.1 MUs. An investigation of the emission decay behavior
      between 1.3 and 300 K gives insight into the nature of the emitting states. At
      temperatures below T ~ 60 K, the decay times of the studied compounds are several
      hundred microseconds long, which indicates that the emission originates from a
      triplet state (T1 state). DFT calculations show that this state is of
      (metal+halide)-to-ligand charge transfer (3)(M+X)LCT character. Investigations at
      1.3 K allow us to gain insight into the three triplet substates, in particular,
      to determine the individual substate decay times being as long as a few
      milliseconds. The zero-field splittings are smaller than 1 or 2 cm(-1). With an
      analysis of these data, conclusions about the effectiveness of spin-orbit
      coupling (SOC) can be drawn. Interestingly, the large differences of SOC
      constants of the halides are not obviously displayed in the triplet state
      properties. With a temperature increase from T ~ 60 to 300 K, a significant
      decrease of the emission decay time by almost 2 orders of magnitude is observed,
      and at ambient temperature, the decay times amount only to ~4-7 MUs without a
      significant reduction of the emission quantum yields. This drastic decrease of
      the (radiative) decay time is a result of the thermal population of a short-lived
      singlet state (S1 state) that lies energetically only a few hundred wavenumbers
      (460-630 cm(-1)) higher than the T1 state. Such an emission mechanism corresponds
      to a thermally activated delayed fluorescence (TADF). At ambient temperature,
      almost only a delayed fluorescence (~98%) is observed. Compounds showing this
      mechanism are highly attractive for applications in OLEDs or LEECs as, in
      principle, it is possible to harvest all singlet and triplet excitons for the
      generation of light in the lowest excited singlet state. This effect represents
      the singlet harvesting mechanism. 

PMID- 23967802
TI  - beta-Lactamase inhibitors: a review of the patent literature (2010 - 2013).
AB  - INTRODUCTION: New beta-lactamases with ever-broadening substrate specificity are
      rapidly disseminating globally, thereby threatening the efficacy of our best beta
      lactam antibiotics. A potential solution to this problem is the development of
      wide-spectrum beta-lactamase inhibitors, to be coadministered with existing and
      new beta-lactams. AREAS COVERED: This review covers the patent literature in the
      beta-lactamase inhibitor area roughly from 2010 to 2013, with prior background
      being provided in the cases of key inhibitors and antibiotic/inhibitor
      combinations. An effort has been made to identify the strong and weak points of
      each inhibitor and combination. EXPERT OPINION: Research in this field has become
      increasingly diverse, with several non-beta-lactam inhibitor classes now assuming
      importance. The emphasis has been on finding inhibitors of AmpC, the extended
      spectrum beta-lactamases and class A and D carbapenemases that can demonstrate
      synergy with antibiotics against resistant Gram-negative pathogens. Progress has
      been made. Metallo-beta-lactamases (MBL)-mediated resistance, however, represents
      an unmet challenge. The author believes that it will be extremely difficult to
      generate a selective, commercially viable MBL inhibitor with sufficient activity
      against NDM-1 and that alternate design strategies will need to be employed.

PMID- 23967803
TI  - Improving cardiac autonomic function following myocardial infarction: the case
      for anticholinesterase drugs.

PMID- 23967804
TI  - When your smoking is not just about you: antismoking advertising, interpersonal
      pressure, and quitting outcomes.
AB  - The authors investigated the potential for antismoking advertising to generate
      interpersonal pressure on smokers to quit using the Cancer Institute NSW's
      Tobacco Tracking Survey, a telephone tracking survey of adult smokers conducted
      throughout the year with approximately 50 interviews per week (N = 5,448). The
      survey includes questions relating to recently broadcast antismoking
      advertisements, including whether smokers have received pressure from family and
      friends as a result of their seeing the advertisements. The authors conducted
      multivariate logistic regression analyses to predict: (a) receiving ad-stimulated
      interpersonal pressure; and (b) quitting outcomes. All analyses controlled for
      smoker characteristics and potential exposure to the advertisements. Compared
      with ads coded as having a low level of emotion (by independent coders), ads
      coded as highly emotional were more likely to have generated interpersonal
      pressure. Ad-stimulated interpersonal pressure was associated with an increased
      likelihood of recent quit attempts and with salient quitting thoughts, with a
      greater effect on quitting thoughts for interpersonal pressure generated by
      highly and moderately emotional ads. These results support previous research
      suggesting that highly emotional antismoking ads with personal stories or graphic
      imagery are effective in promoting smoking cessation, and these results help to
      identify communication processes that contribute to the ads' success. 

PMID- 23967805
TI  - Molecular structure of starches from maize mutants deficient in starch synthase
      III.
AB  - Molecular structures of starches from dull1 maize mutants deficient in starch
      synthase III (SSIII) with a common genetic background (W64A) were characterized
      and compared with the wild type. Amylose content with altered structure was
      higher in the nonwaxy mutants (25.4-30.2%) compared to the wild type maize
      (21.5%) as revealed by gel permeation chromatography. Superlong chains of the
      amylopectin component were found in all nonwaxy samples. Unit chain length
      distribution of amylopectins and their phi,beta-limit dextrins (reflecting
      amylopectin internal structure) from dull1 mutants were also characterized by
      anion-exchange chromatography after debranching. Deficiency of SSIII led to an
      increased amount of short chains (DP <=36 in amylopectin), whereas the content of
      long chains decreased from 8.4% to between 3.1 and 3.7% in both amylopectin and
      phi,beta-limit dextrins. Moreover, both the external and internal chain lengths
      decreased, suggesting a difference in their cluster structures. Whereas the molar
      ratio of A:B-chains was similar in all samples (1.1-1.2), some ratios of chain
      categories were affected by the absence of SSIII, notably the ratio of
      "fingerprint" A-chains to "clustered" A-chains. This study highlighted the
      relationship between SSIII and the internal molecular structure of maize starch. 

PMID- 23967806
TI  - Consumption of alcoholic beverages and cognitive decline at middle age: the
      Doetinchem Cohort Study.
AB  - Accelerated cognitive decline increases the risk of dementia. Slowing down the
      rate of cognitive decline leads to the preservation of cognitive functioning in
      the elderly, who can live independently for a longer time. Alcohol consumption
      may influence the rate of cognitive decline. The aim of the present study was to
      evaluate the associations between the total consumption of alcoholic beverages
      and different types of alcoholic beverages and cognitive decline at middle age.
      In 2613 men and women of the Doetinchem Cohort Study, aged 43-70 years at
      baseline (1995-2002), cognitive function (global cognitive function and the
      domains memory, speed and flexibility) was assessed twice, with a 5-year time
      interval. In linear regression analyses, the consumption of different types of
      alcoholic beverages was analysed in relation to cognitive decline, adjusting for
      confounders. We observed that, in women, the total consumption of alcoholic
      beverages was inversely associated with the decline in global cognitive function
      over a 5-year period (P for trend = 0.02), while no association was observed in
      men. Regarding the consumption of different types of alcoholic beverages in men
      and women together, red wine consumption was inversely associated with the
      decline in global cognitive function (P for trend < 0.01) as well as memory (P
      for trend < 0.01) and flexibility (P for trend = 0.03). Smallest declines were
      observed at a consumption of about 1.5 glasses of red wine per d. No other types
      of alcoholic beverages were associated with cognitive decline. In conclusion,
      only (moderate) red wine consumption was consistently associated with less strong
      cognitive decline. Therefore, it is most likely that non-alcoholic substances in
      red wine are responsible for any cognition-preserving effects.

PMID- 23967808
TI  - Editor's Note: Attention as a Cognitive Neurosystem.

PMID- 23967807
TI  - Clinical profile, morbidity, and outcome of adult-onset generalized pustular
      psoriasis: analysis of 102 cases seen in a tertiary hospital in Johor, Malaysia.
AB  - BACKGROUND: Generalized pustular psoriasis (GPP) is a severe but rare variant of
      psoriasis. Our objective is to review the clinical profile, comorbidities, and
      outcome of patients with GPP. MATERIALS AND METHODS: A retrospective note review
      of all patients with adult-onset GPP. RESULTS: A total of 102 patients with adult
      onset GPP were diagnosed between 1989 and November 2011, with a female to male
      ratio of 2 : 1. The mean age at onset of GPP was 40.9 years (range: 21-81 years).
      Acute GPP was the most common variant seen (95 cases), followed by four localized
      variants of GPP and three with annular pustular psoriasis. Fever and painful skin
      were present in 89% of patients, arthritis in 34.7%, and leukocytosis in 78.4%.
      Common triggers were systemic steroids (45 cases), pregnancy (17 cases), and
      upper respiratory tract infections (16 cases). A positive family history of
      psoriasis and GPP was present in 29% and 11%, respectively. Comorbidities
      included obesity (42.9%), hypertension (25.7%), hyperlipidemia (25.7%), and
      diabetes mellitus (23.7%). The mean duration of admission and pustular flare for
      acute GPP was 10.3 days (range: 3-44 days) and 16 days (range: 7-60 days),
      respectively. Fifty-four patients responded to systemic retinoid, 21 to
      methotrexate, eight to cyclosporine, and one to adalimumab, but recurrences were
      common. CONCLUSIONS: Our study confirms the poor response of GPP to currently
      available anti-psoriatic agents, with frequent flare-ups. There is a need for a
      more effective targeted therapy for this condition.

PMID- 23967809
TI  - A cognitive-anatomical approach to attention in lexical access.
AB  - Recent PET studies have suggested a specific anatomy for feature identification,
      visual word forms and semantic associations. Our studies seek to explore the time
      course of access to these systems by use of reaction time and scalp electrical
      recording. Target detection times suggest that different forms of representation
      are involved in the detection of letter features, feature conjunctions (letters),
      and words. Feature search is fastest at the fovea and slows symmetrically with
      greater foveal eccentricity. It is not influenced by lexicality. Detecting a
      letter case (conjunction) shows a left to right search which differs between
      words and consonant strings. Analysis of scalp electrical distribution suggest an
      occipito-temporal distribution for the analysis of visual features (right sided)
      and for the visual word form discrimination (left sided). These fit with the PET
      results, and suggest that the feature related analysis begins within the first
      100 millisec and the visual word form discriminates words from strings by about
      200 msec. Lexical decision instructions can modify the computations found in both
      frontal and posterior areas. 

PMID- 23967810
TI  - Role of Anterior and Posterior Attention Networks in Hemispheric Asymmetries
      during Lexical Decisions.
AB  - The role of the left and right hemisphere was examined during semantic priming by
      antonyms, remote associates, and unrelated words. Targets presented directly to
      the left hemisphere showed an early facilitation and a late developing
      inhibition, while targets presented directly to the right hemisphere showed a
      late developing facilitation of strong and weak associations and little evidence
      of inhibition. When a visual cue was given prior to each target word, reaction
      times were facilitated equally in both visual fields and for all prime target
      relationships. When the priming task was combined with shadowing, reaction times
      generally increased and all evidence of inhibition in left hemisphere processing
      disappeared. This supported the idea that the inhibition found in the left
      hemisphere was due to its interaction with the anterior attention network. 

PMID- 23967811
TI  - Extrageniculate contributions to reflex visual orienting in normal humans: a
      temporal hemifield advantage.
AB  - Evidence is presented that the phylogenetically older retin-otectal pathway
      contributes to reflex orienting of visual attention in normal human subjects. The
      study exploited a lateralized neuroanatomic arrangement of retinotectal pathways
      that distinguishes them from those of the geniculostriate system; namely, more
      direct projections to the colliculus from the temporal hemifield. Subjects were
      tested under monocular viewing conditions and responded to the detection of a
      peripheral signal by making either a saccade to it or a choice reaction time
      manual keypress. Attention was summoned by noninformative peripheral precues, and
      the benefits and costs of attention were calculated relative to a central precue
      condition. Both the benefits and costs of orienting attention were greater when
      attention was summoned by signals in the temporal hemifield. This temporal
      hemifield advantage was present for both saccade and manual responses. These
      findings converge with observations in patients with occipital and midbrain
      lesions to show that the phylogenetically older retinotectal pathway retains an
      important role in controlling visually guided behavior; and they demonstrate the
      usefulness of temporal-nasal hemifield asymmetries as a marker for investigating
      extrageniculate vision in humans. 

PMID- 23967812
TI  - Right hemisphere processing superiority during sustained visual attention.
AB  - Normal subjects showed a right hemisphere processing superiority in reaction
      times to visual stimuli under conditions of sustained visual attention. This
      asymmetry was predicted based on findings in studies of blood flow, clinical
      populations, and physiology on lateralization of the noradrenergic system. The
      asymmetry was eliminated when an auditory event was delivered simultaneously with
      the visual target suggesting a common pathway between voluntary sustained
      alerting and more automatic alerting effects of external stimuli. The act of
      sustaining alertness also interacted with covert orienting of attention as would
      be expected if alerting influenced the efficiency of covert shifts of attention. 

PMID- 23967813
TI  - Components of visual orienting in early infancy: contingency learning,
      anticipatory looking, and disengaging.
AB  - Three aspects of the development of visual orienting in infants of 2, 3, and 4
      months of age are examined in this paper. These are the age of onset and sequence
      of development of (1) the ability to readily disengage gaze from a stimulus, (2)
      the ability to consistently show "anticipatory" eye movements, and (3) the
      ability to use a central cue to predict the spatial location of a target. Results
      indicated that only the 4--month-old group was easily able to disengage from an
      attractive central stimulus to orient toward a simultaneously presented target.
      The 4--month-old group also showed more than double the percentage of
      "anticipatory" looks than did the other age groups. Finally, only the 4--month
      old group showed significant evidence of being able to acquire the contingent
      relationship between a central cue and the spatial location (to the right or to
      the left) of a target. Measures of anticipatory looking and contingency learning
      were not correlated. These findings are, in general terms, consistent with the
      predictions of matura-tional accounts of the development of visual orienting. 

PMID- 23967814
TI  - The development of inhibition of return in early infancy.
AB  - The posterior visual spatial attention system involves a number of separable
      computations that allow orienting to visual locations. We have studied one of
      these computations, inhibition of return, in 3-, 4-, 6-, 12-, and 18--month-old
      infants and adults. Our results indicate that this computation develops rapidly
      between 3 and 6 months, in conjunction with the ability to program eye movements
      to specific locations. These findings demonstrate that an attention computation
      involving the mid-brain eye movement system develops after the third month of
      life. We suggest how this development might influence the infant's ability to
      represent and expect visual objects. 

PMID- 23967815
TI  - Development of spontaneous alternation in infancy.
AB  - Spontaneous alternation is a reduced tendency to return to the same location on
      successive trials. It is measured in rats in a T maze and is thought to depend on
      an intact hippocampus. In human infants, we measured alternation in the tendency
      to reach toward one of two identical toys placed in locations to the left and
      right of midline. Infants at 6 months returned to the same side as frequently as
      they alternated, but 18--month-old infants showed a significant alternation
      pattern. At 6 months, infants show inhibition of return, but do not show
      alternation in motor behavior; at 18 months, infants show both, but they are
      negatively related. These data suggest that preference for novelty may rest on
      different internal mechanisms even in quite similar tasks, and suggest that
      whereas inhibition of return is related to control by the posterior attention
      network, spontaneous alternation may be related to inhibitory control by the
      anterior attention network. 

PMID- 23967816
TI  - Impaired velocity perception in patients with lesions of the cerebellum.
AB  - In three psychophysical experiments, cerebellar patients were impaired in making
      perceptual judgments of the velocity of moving stimuli. Performance was normal
      when the judgment concerned the position of the stimuli (Experiment 1). The
      dissociation between the velocity and position tasks suggests the cerebellar
      group was selectively impaired in velocity perception. EOG data were obtained in
      Experiments 2 and 3 to assess whether the deficit was oculomotor in origin.
      Perceptual errors were not correlated with the occurrence of intrusive eye
      movements. These results provide a novel demonstration of the role of the
      cerebellum in perceptual functions that require precise timing. 

PMID- 23967817
TI  - Timing and force control deficits in clumsy children.
AB  - This study investigated the link between cognitive processes and neural
      structures involved in motor control. Children identified as clumsy through
      clinical assessment procedures were tested on tasks involving movement timing,
      perceptual timing, and force control. The clumsy children were divided into two
      groups: those with soft neurological signs associated with cerebellar dysfunction
      and those with soft neurological signs associated with dysfunction of the basal
      ganglia. A control group of age-matched children who did not exhibit evidence of
      clumsiness or soft neurological signs was also tested. The results showed a
      double dissociation between the two groups of clumsy children and the tests of
      timing and force. Clumsy children with cerebellar signs were more variable when
      attempting to tap a series of equal intervals. They were also more variable on
      the time perception task, indicating a deficit in motor and perceptual timing.
      The clumsy children with basal ganglia signs were unimpaired on the timing tasks.
      However, they were more variable in controlling the amplitude of isometric force
      pulses. These results support the hypothesis that the control of time and force
      are separate components of coordination and that these computations are dependent
      on different neural systems. 

PMID- 23967819
TI  - The organization of learning.

PMID- 23967818
TI  - Lateralized control of eye movements in attention deficit hyperactivity disorder.
AB  - How does a complex syndrome that involves abnormalities in impulse control and
      sustained attention influence simple oculomotor responses to visual stimuli? We
      found that normal children, like adults, were faster in moving their eyes in
      directions controlled by the right cerebral hemisphere under conditions where
      there was no warning of the impending target. ADHD children did not show this
      asymmetry. We speculate that this result reflects a deficit in the vigilance
      network that serves to maintain the alert state. 

PMID- 23967820
TI  - Interview with floyd e. Bloom.

PMID- 23967821
TI  - Metabolic and regulatory rearrangements underlying glycerol metabolism in
      Pseudomonas putida KT2440.
AB  - While the natural niches of the soil bacterium Pseudomonas putida are unlikely to
      include significant amounts of free glycerol as a growth substrate, this
      bacterium is genetically equipped with the functions required for its metabolism.
      We have resorted to deep sequencing of the transcripts in glycerol-grown P.
      putida KT2440 cells to gain an insight into the biochemical and regulatory
      components involved in the shift between customary C sources (e.g. glucose or
      succinate) to the polyol. Transcriptomic results were contrasted with key
      enzymatic activities under the same culture conditions. Cognate expression
      profiles revealed that genes encoding enzymes of the Entner-Doudoroff route and
      other catabolic pathways, e.g. the gluconate and 2-ketogluconate loops, were
      significantly downregulated on glycerol. Yet, the compound simultaneously
      elicited a gluconeogenic response that indicated an efficient channelling of C
      skeletons back to biomass build-up through the glyoxylate shunt rather than
      energization of the cells through downwards pathways, i.e. tricarboxylic acid
      cycle and oxidative phosphorylation. The simultaneous glycolytic and
      gluconeogenic metabolic regimes on glycerol, paradoxical as they seem, make sense
      from an ecological point of view by favouring prevalence versus exploration. This
      metabolic situation was accompanied by a considerably low expression of stress
      markers as compared with other C sources.

PMID- 23967822
TI  - Epidemiology of melasma in Brazilian patients: a multicenter study.
AB  - BACKGROUND: Melasma is an acquired, irregularly patterned, light to dark-brown
      hypermelanosis, with symmetric distribution mostly over the face. The aim of this
      study was to evaluate clinical characteristics and factors related to melasma in
      Brazilian patients. METHODS: This was a cross-sectional, multicenter study
      performed in Brazil. Investigators examined and questioned 953 patients over 18
      years of age on clinical characteristics and other factors related to their
      melasma. RESULTS: Melasma was more prevalent in women (97.5%) and in Fitzpatrick
      skin phototypes II (12.8%), III (36.3%), and IV (39.7%). Skin phototypes II and
      III and family history of melasma had early onset of the disorder when compared
      with skin phototypes IV, V, and VI (P<0.0001). Similar results were also observed
      when these same groups were compared with the absence of family history
      (P<0.0001). Extra-facial melasma was more frequent in postmenopausal women
      compared with those who were not experiencing menopause (14.2% vs. 3.5%,
      P<0.0001). CONCLUSIONS: Data suggested that the age of melasma onset are related
      to skin phototypes and family history. Additionally, extra-facial melasma was
      more common in menopausal women. This is the first study on the epidemiology of
      melasma in Brazil involving a large sample of the population. These data can be a
      source of new relevant research on the cause and development of melasma.

PMID- 23967839
TI  - Diet quality from pre-school to school age in Brazilian children: a 4-year follow
      up in a randomised control study.
AB  - A previous study demonstrated that dietary counselling for mothers during the
      first year of life improved overall diet quality of children at pre-school age in
      a low-income population. Thus, the objective of the present study was to assess
      the long-term effect of this intervention on diet quality of children at school
      age and examine the tracking of dietary intake throughout childhood. The present
      study was a follow-up of a randomised controlled trial with children who were
      assessed at 3-4 years (n 345) and 7-8 years (n 307) of age. We collected two 24 h
      dietary recalls and assessed diet quality using the Healthy Eating Index (HEI).
      Analyses were performed by group using a paired t test and a Student's t test for
      independent samples. Diet quality did not differ between the intervention and
      control groups at 7-8 years of age (HEI score 65.2 (SD 9.5) v. 64.9 (SD 8.5)).
      Regarding changes in diet quality from pre-school to school age, we observed the
      tracking of diet quality in the control group and the loss of the intervention
      effect in the intervention group. In both groups, the score for fruit and milk
      intake decreased, while that for saturated fat and dietary variety intake
      increased. The score for the intakes of grains, meat and legumes, and total fat
      remained constant for all children. The present data provide evidence that diet
      quality tracks during childhood since the total HEI score did not differ over
      time in the control group. The decrease in score for some HEI components did not
      affect the overall diet quality due to the increase in score for other HEI
      components.

PMID- 23967823
TI  - The prevalence of depression and anxiety among Chinese adults with cancer: a
      systematic review and meta-analysis.
AB  - BACKGROUND: A lot of empirical studies have been conducted to evaluate the
      prevalence of depression and anxiety among Chinese adults with cancer. We aimed
      to conduct a meta-analysis in order to evaluate the prevalence and odds ratios of
      depression and anxiety in Chinese adults with cancer compared with those without.
      METHODS: The three most comprehensive computerized Chinese academic databases
      CNKI, Wangfang and Vip databases-were systematically screened through September
      2012. PubMed and Web of Science (SCIE) were also searched from their inception
      until September 2012 without language restrictions, and an internet search was
      also used. Case-control studies assessing the prevalence of depression and
      anxiety among Chinese adults with cancer were analyzed. Study selection and
      appraisal were conducted independently by three authors. The non-weighted
      prevalence, pooled random-effects estimates of odds ratio (OR) and 95% confidence
      intervals (CI) were all calculated. RESULTS: Seventeen eligible studies with a
      total of 3497 subjects were included. The prevalence of depression and anxiety
      were significantly higher in adults with cancer compared with those without
      (Depression: 54.90% vs. 17.50%, OR = 7.85, 95% CI = 5.56-11.07, P = 0.000;
      Anxiety: 49.69% vs. 18.37%, OR = 6.46, 95% CI = 4.36-9.55, P = 0.000), the same
      situation was also observed in subgroup of control groups, assessment methods and
      cancer types. Although no difference of depression was observed in studies
      utilizing clinical diagnosis compared with self-report, the OR of anxiety in
      adults with cancer compared with those without was higher in studies utilizing
      clinical diagnosis (OR = 8.42, 95% CI = 4.83-14.70) than self-reports (OR = 5.83,
      95% CI = 3.64-9.34). The ORs of depression and anxiety in cancer patients
      compared with disease group (Depression: OR = 6.03, 95% CI = 4.23-8.61; Anxiety:
      OR = 4.40, 95% CI = 3.05-6.36) were lower than in those compared with normal
      group (Depression: OR = 13.58, 95% CI = 6.26-29.46; Anxiety: OR = 15.47, 95% CI =
      10.00-23.95). CONCLUSIONS: We identified high prevalence rates of depression and
      anxiety among Chinese adults with cancer. The findings support that the
      prevalence of depression and anxiety among adults with cancer should receive more
      attention in Chinese medical settings.

PMID- 23967852
TI  - Management of incus long process defects: incus interposition versus
      incudostapedial rebridging with bone cement.
AB  - OBJECTIVE: This study aimed to compare the hearing results of incus interposition
      and bone cement ossiculoplasty in patients with incus long process defects.
      MATERIALS AND METHODS: Ninety-nine patients with incus long process defects were
      included. Incus interposition was performed in 49 patients (group 1) and bone
      cement ossiculoplasty was performed in 50 patients (group 2). Group 1 included 29
      female and 20 male patients, with a mean age +/- standard deviation of 29.43 +/-
      12.5 years (range, 8-58 years). Group 2 comprised 32 female and 18 male patients,
      with a mean age +/- standard deviation of 29.1 +/- 14.89 years (range, 8-67
      years). RESULTS: The mean hearing gain +/- standard deviation was 15.2 +/- 9.01
      dB in group 1 and 19.36 +/- 9.08 dB in group 2. Hearing gain was significantly
      greater in the bone cement group than in the incus interposition group (p =
      0.0186). Successful hearing results (i.e. air-bone gap < 20 dB) were achieved by
      63.2 per cent of group 1 patients and 78 per cent of group 2 patients.
      CONCLUSION: Incus interposition and bone cement ossiculoplasty are safe and
      reliable methods with which to manage incus long process defects. Bone cement
      ossiculoplasty gives a greater hearing gain in appropriate cases.

PMID- 23967853
TI  - The psychophysical attributes of heat-induced pain and their relationships to
      neural mechanisms.
AB  - During the last two decades there has been a proliferation of studies evaluating
      the psychophysical and neural attributes of heat-induced pain. Experiments using
      radiant and contact heat-induced pain have produced different observations
      thereby broadening our appreciation of the importance of acknowledging how a
      noxious heat stimulus is delivered; moreover manipulations of stimulus parameters
      have now provided a foundation for understanding the underlying neural mechanisms
      of heat-induced pain and their biological significance. The psychophysical
      attributes of heat-induced pain include highly reliable thresholds for most body
      regions, minimal adaptation to maintained noxious stimuli, an exquisite
      sensitivity to small changes in stimulus intensity, slow temporal summation for
      some types of heat-induced pain (i.e., second pain) but not for others (i.e.,
      first pain), spatial summation---especially for suprathreshold noxious
      temperatures---and the perceived spread of pain well beyond the actual body area
      stimulated (i.e., radiation). The present body of information indicates that the
      pain system is optimally adapted for conveying precise information about
      intensity, and is less concerned with other stimulus features, such as spatial
      patterns or boundaries. 

PMID- 23967854
TI  - N400 to semantically anomalous pictures and words.
AB  - The N400 component of the human event-related brain potential appears to be
      related to violations of semantic expectancy during language comprehension. The
      present experiment investigated whether the N400 is related specifically to
      activity in a language system or is an index of a conceptual system that is
      accessed by both pictures and words. Sentences were visually presented one word
      at a time with the last word being replaced in one condition by a line drawing
      representing the same concept (eg, the word "socks" was replaced by a picture of
      socks). The N400 recorded in the Pictures Condition was found to be identical to
      the N400 generated by words in terms of amplitude, scalp distribution, and
      latency. These results suggest that the N400 is an index of activity in a
      conceptual memory that is accessed by both pictures and words. 

PMID- 23967855
TI  - Dissociation of object and spatial vision in human extrastriate cortex: age
      related changes in activation of regional cerebral blood flow measured with [(15)
      o]water and positron emission tomography.
AB  - We previously reported selective activation of regional cerebral blood flow
      (rCBF) in occipitotemporal cortex during a face matching task (object vision) and
      activation in superior parietal cortex during a dot-location matching task
      (spatial vision) in young subjects, The purpose of the present study was to
      determine the effects of aging on these extrastriate visual processing systems.
      Eleven young (mean age 27 +/- 4 years) and nine old (mean age 72 +/- 7 years)
      male subjects were studied. Positron emission tomographic scans were performed
      using a Scanditronix PC1024-7B tomograph and H2(15)O to measure rCBF. To locate
      brain areas that were activated by the visual tasks, pixel-by-pixel difference
      images were computed between images from a control task and images from the face
      and dot-location matching tasks. Both young and old subjects showed rCBF
      activation during face matching primarily in occipitotemporal cortex, and
      activation of superior parietal cortex during dot-location matching. Statistical
      comparisons of these activations showed that the old subjects had more activation
      of occipitotemporal cortex during the spatial task and more activation of
      superior parietal cortex during the object task than did the young subjects.
      These results show less functional separation of the dorsal and ventral visual
      pathways in older subjects, and may reflect an age-related reduction in the
      processing efficiency of these visual cortical areas. 

PMID- 23967856
TI  - Direct and Indirect Cooperation between Temporal and Parietal Networks for
      Invariant Visual Recognition.
AB  - A new type of biologically inspired multilayered network is proposed to model the
      properties of the primate visual system with respect to invariant visual
      recognition (IVR). This model is based on 10 major neurobiological and
      psychological constraints. The first five constraints shape the architecture and
      properties of the network. 1. The network model has a Y-like double-branched
      multilayered architecture, with one input (the retina) and two parallel outputs,
      the "What" and the "Where," which model, respectively, the temporal pathway,
      specialized for "object" identification, and the parietal pathway specialized for
      "spatial" localization. 2. Four processing layers are sufficient to model the
      main functional steps of primate visual system that transform the retinal
      information into prototypes (object-centered reference frame) in the "What"
      branch and into an oculomotor command in the "Where" branch. 3. The distribution
      of receptive field sizes within and between the two functional pathways provides
      an appropriate tradeoff between discrimination and invariant recognition
      capabilities. 4. The two outputs are represented by a population coding: the
      ocular command is computed as a population vector in the "Where" branch and the
      prototypes are coded in a "semidistributed" way in the "What" branch. In the
      intermediate associative steps, processing units learn to associate prototypes
      (through feedback connections) to component features (through feedforward ones).
      5. The basic processing units of the network do not model single cells but model
      the local neuronal circuits that combine different information flows organized in
      separate cortical layers. Such a biologically constrained model shows shift
      invariant and size-invariant capabilities that resemble those of humans
      (psychological constraints): 6. During the Learning session, a set of patterns
      (26 capital letters and 2 geometric figures) are presented to the network: a
      single presentation of each pattern in one position (at the center) and with one
      size is sufficient to learn the corresponding prototypes (internal
      representations). These patterns are thus presented in widely varying new sizes
      and positions during the Recognition session: 7. The "What" branch of the network
      succeeds in immediate recognition for patterns presented in the central zone of
      the retina with the learned size. 8. The recognition by the "What" branch is
      resistant to changes in size within a limited range of variation related to the
      distribution of receptive field (RF) sizes in the successive processing steps of
      this pathway. 9. Even when ocular movements are not allowed, the recognition
      capabilities of the "What" branch are unaffected by changing positions around the
      learned one. This significant shift-invariance of the "What" branch is also
      related to the distribution of RF sizes. 10. When varying both sizes and
      locations, the "What" and the "Where" branches cooperate for recognition: the
      location coding in the "Where" branch can command, under the control of the
      "What" branch, an ocular movement efficient to reset peripheral patterns toward
      the central zone of the retina until successful recognition. This model results
      in predictions about anatomical connections and physiological interactions
      between temporal and parietal cortices. 

PMID- 23967857
TI  - Facilitation of working memory in humans by a d2 dopamine receptor agonist.
AB  - Recent studies on the neurobiology of cognition have focused on the ability of
      the prefrontal cortex (PFC) to support processes of working memory, i.e, mnemonic
      processes by which information relevant for a correct response is temporarily
      maintained to be reevaluated or updated on a trial-by-trial basis. Of most recent
      interest is the role played by dopamine (DA) in spatial working memory processes
      of the principal sulcal region of the PFC. Although D1 DA receptors appear to
      modulate these mnemonic processes in monkeys, several lines of research suggest
      that D2 DA receptors could also be relevant to cognitive functions. Therefore, we
      assessed the effects of a specific D2 receptor agonist (bromocriptine) and
      placebo on visuospatial delayed response performance in human subjects. During
      delay periods of 0 or 8 sec, subjects were required to remember the spatial
      location of rapidly presented visual cues displayed in peripheral vision within a
      360 degrees  circumference. The extent to which D2 receptor activation by
      bromocriptine facilitated working memory in the 8-sec delay condition relative to
      placebo performance was assessed. As a means of providing validation of
      bromocriptine's D2 receptor effect, maximum inhibition of prolactin (PRL)
      secretion, which is inhibited specifically by activation of D2 receptor sites,
      was determined. Additionally, tasks having no working memory component were
      administered to rule out nonspecific effects of bromocriptine on sensory,
      arousal, attentional, and motor factors. Results demonstrated a significant
      facilitatory effect of bromocriptine on spatial delayed response performance
      (i.e., 8-sec delay performance). Results could not be explained by nonspecific
      effects of bromocriptine. Thus, findings of this study suggest that spatial
      working memory is facilitated by D2 receptor activation. The role that DA may
      play in human cognitive processes is discussed within the larger theoretical
      framework of DA's general role in the facilitation of goal-directed behavior. In
      the case of cognition, DA may facilitate processes that serve to guide motivated
      behavior through complex environments. 

PMID- 23967858
TI  - Event-related potentials and recognition memory for low- and high-frequency
      words.
AB  - Event-related potentials (ERPs) were recorded while subjects made recognition
      judgments on high- and low-frequency words, half of which had previously been
      presented in an incidental study task. Compared to high-frequency items, low
      frequency words were associated with superior recognition performance, and
      attracted a higher proportion of confident judgments. In the case of the low
      frequency words only, the region of the ERPs post-500 msec evoked by correctly
      classified, previously studied (old) words was more positive-going than was the
      same region of the EWs to nonstudied (new) words. These "old/new" ERP differences
      were larger from electrodes over the left than over the right hemisphere. This
      old/new by frequency interaction held when EWs were formed only from words that
      attracted confident judgments. It is argued that these data are consistent with
      the ideas that (1) post-500 msec "old/ new" EW differences in recognition memory
      tasks reflect differences in old and new words' levels of relative familiarity,
      and (2) the recognition memory advantage for low-frequency words results, at
      least in part, from the higher level of relative familiarity engendered at test
      by previously studied low-frequency items. The data are interpreted as providing
      support for "two-process" models of recognition memory. 

PMID- 23967859
TI  - Is cognitive neuropsychology possible?
AB  - Cognitive neuropsychology's domain of inquiry concerns the structure of normal
      perceptual, motor, and cognitive processes. As such, it constitutes a branch of
      cognitive science. Cognitive neuropsychology differs from other branches of
      cognitive science only by the type of observation that it uses in developing and
      evaluating theories of normal cognition. The data used in cognitive
      neuropsychology are the patterns of performance produced by brain-damged
      subjects. Because the basic data used in cognitive neuropsychology are the result
      of a biological manipulation-a brain lesion-these data will be relevant to claims
      about the functional organization of the brain. Hence, cognitive neuropsychology
      may also be considered to be a branch of cognitive neuroscience. However, in this
      paper I will be concerned with an assessment of research programs whose principal
      or only aim is to constrain theories of normal cognitive functioning through the
      analysis of acquired disorders of cognition. Following a brief discussion of the
      basic assumptions that motivate cognitive neuropsychological research, I consider
      Kosslyn and Van Kleeks (1990) claim that the study of brain-damaged subjects for
      the purpose of constraining theories of normal cognitive processing cannot lead
      to meaningful conclusions unless the theories are directly cast in terms of
      anatomical and physiological facts. I argue that these authors conflated
      criticisms that may apply to any empirical science with criticisms that may apply
      specifically to cognitive neuropsychology. Separate consideration of the
      criticisms specific to cognitive neuropsychology reveals that these are
      unfounded. The main point of this discussion is to emphasize the pragmatic
      character of the motivation for using impaired performance to constrain theories
      of normal cognition. The usefulness of cognitive neuropsychological research is
      illustrated through specific examples. 

PMID- 23967860
TI  - Is cognitive neuropsychology plausible? The perils of sitting on a one-legged
      stool.
AB  - We distinguish between strong and weak cognitive neuropsychology, with the former
      attempting to provide direct insights into the nature of information processing
      and the latter having the more modest goal of providing constraints on such
      theories. We argue that strong cognitive neuropsychology, although possible, is
      unlikely to succeed and that researchers will fare better by combining
      behavioral, computational, and neural investigations. Arguments offered by
      Caramazza (1992) in defense of strong neuropsychology are analyzed, and examples
      are offered to illustrate the power of alternative points of view. 

PMID- 23967861
TI  - Inhibitors of influenza viruses replication: a patent evaluation (WO2013019828).
AB  - A series of compounds incorporating two aromatic heterocycles were prepared as
      inhibitors of influenza virus replication in the patent. Some of them presented
      potent activity against influenza virus in Madin-Darby canine kidney (MDCK) cells
      and in influenza therapeutic mouse model. These compounds in the patent were also
      defined to be pharmaceutically acceptable salts and pharmaceutical compositions
      that were claimed to be useful for treating influenza. In view of the threat of
      influenza pandemic, it is necessary to discover new anti-influenza drugs.
      Although there is a lack of essential biological data and the molecular
      mechanisms are not clear, these compounds with potent antiviral activity stand
      for a new type of anti-influenza agents and deserve further studies. 

PMID- 23967862
TI  - Cultural universality of domestic abuse. Editorial.

PMID- 23967863
TI  - Honorary address by Her Royal Highness Princess Bajrakitiyabha at the 19th
      International Council on Women's Health Issues (ICOWHI) Congress on "Women's
      Health 2012: Partnering for a Brighter Global Future".

PMID- 23967865
TI  - Prediction of metachronous multiple primary cancers following the curative
      resection of gastric cancer.
AB  - BACKGROUND: Due to improved survival rate, gastric cancer (GC) patients have an
      increased risk of developing multiple primary cancer (MPC). The purpose of this
      study is to evaluate the clinicopathological features of MPC and to generate
      useful tools for the prediction of metachronous MPC following gastrectomy.
      METHODS: 3066 patients who underwent curative resection of GC were reviewed
      retrospectively, based on the clinical information and the medical record.
      RESULTS: The 5-year incidence of MPC was 2.5%. Of these, 54.3% had a metachronous
      MPC, while 45.7% had a synchronous MPC. The most prevalent site of metachronous
      MPC was the colorectum (26.3%), followed by lung (23.7%) and liver (18.4%).
      Multivariate logistic regression analysis revealed that old age at the time of GC
      diagnosis (>=60 years), early stage of GC (stage I and II), and multiplicity of
      GC at the time of gastrectomy were independent predictive factors for
      metachronous MPC. GC patients with either metachronous or synchronous MPC showed
      poorer survival than patients without MPC. In addition, patients with a
      metachronous MPC showed late survival disadvantage, while patients with a
      synchronous MPC showed early survival disadvantage. Furthermore, we were able to
      develop and internally validate a nomogram to predict the metachronous MPC after
      curative gastrectomy (C-index = 0.72). CONCLUSION: Patients at high risk of
      developing metachronous MPC after curative resection of GC were identified.
      Individual risk of developing metachronous MPC could be predicted by a novel
      nomogram. Further external validation with independent patient cohorts is
      required to improve the accuracy of prediction.

PMID- 23967866
TI  - Cohesin loading factor Nipbl localizes to chromosome axes during mammalian
      meiotic prophase.
AB  - BACKGROUND: Sister chromatid cohesion mediated by the cohesin complex is
      essential for accurate chromosome segregation during mitosis and meiosis. Loading
      of cohesin onto chromosomes is dependent on another protein complex called
      kollerin, containing Nipbl/Scc2 and Mau2/Scc4. Nipbl is an evolutionarily
      conserved large protein whose haploinsufficiency in humans causes a developmental
      disorder called Cornelia de Lange syndrome. Although the function of Nipbl
      homologues for chromosome cohesion in meiotic cells of non-vertebrate models has
      been elucidated, Nipbl has not been characterized so far in mammalian
      spermatocytes or oocytes. FINDINGS: Here we describe our analyses on the
      expression and localization of Nipbl in nuclei of mouse spermatocytes and oocytes
      at different stages of meiotic prophase. In both spermatocytes and oocytes we
      found that Nipbl is associated with the axial/lateral element of the synaptonemal
      complex (AE/LE) to which cohesin also localizes. Interestingly, Nipbl in
      spermatocytes, but not in oocytes, dissociates from the AE/LE at mid-pachytene
      stage coincident with completion of DNA double-strand break repair. CONCLUSIONS:
      Our data propose that cohesin loading activity is maintained during early stages
      of meiotic prophase in mammalian spermatocytes and oocytes.

PMID- 23967869
TI  - Chunks of charge: effects at play in the assembly of macromolecules at fluid
      surfaces.
AB  - Large macromolecules with hydrophobic backbones are known to assemble at the
      interface between immiscible liquids. This assembly is often unpredictable
      because of the subtle interplay among hydrophobic interactions, hydrophilic
      solvation, structural constraints, and the thermodynamics of adsorption. In these
      studies, we employ vibrational sum frequency spectroscopy and interfacial tension
      measurements to study the assembly of a simple polyelectrolyte, poly(methacrylic
      acid), as it assembles at the interface between two immiscible liquids,
      specifically, carbon tetrachloride and water. By adjusting the polyelectrolyte
      charge through pH studies and the polymer size through molecular weight studies,
      we demonstrate that charge accumulation in segments of the polymer chains is a
      critical factor in macromolecular interfacial adsorption and desorption. The
      results have implications for related charged macromolecules whose ability to
      assemble between two immiscible fluid media is essential for many biological
      processes, water remediation efforts, and enhanced oil recovery. 

PMID- 23967867
TI  - MicroRNA-503 inhibits the G1/S transition by downregulating cyclin D3 and E2F3 in
      hepatocellular carcinoma.
AB  - BACKGROUND: Increasing evidence indicates that deregulation of microRNAs (miRNAs)
      is involved in tumorigenesis. Downregulation of microRNA-503 has been observed in
      various types of diseases, including cancer. However, the biological function of
      miR-503 in hepatocellular carcinoma (HCC) is still largely unknown. In this study
      we aimed to elucidate the prognostic implications of miR-503 in HCC and its
      pathophysiologic role. METHODS: Quantitative reverse transcriptase polymerase
      chain reaction was used to evaluate miR-503 expression in HCC tissues and cell
      lines. Western blotting was performed to evaluate the expression of the miR-503
      target genes. In vivo and in vitro assays were performed to evaluate the function
      of miR-503 in HCC. Luciferase reporter assay was employed to validate the miR-503
      target genes. RESULTS: miR-503 was frequently downregulated in HCC cell lines and
      tissues. Low expression levels of miR-503 were associated with enhanced malignant
      potential such as portal vein tumor thrombi, histologic grade, TNM stage, AFP
      level and poor prognosis. Multivariate analysis indicated that miR-503
      downregulation was significantly associated with worse overall survival of HCC
      patients. Functional studies showed miR-503 suppressed the proliferation of HCC
      cells by induction of G1 phase arrest through Rb-E2F signaling pathways, and thus
      may function as a tumor suppressor. Further investigation characterized two cell
      cycle-related molecules, cyclin D3 and E2F3, as the direct miR-503 targets.
      CONCLUSION: Our data highlight an important role for miR-503 in cell cycle
      regulation and in the molecular etiology of HCC, and implicate the potential
      application of miR-503 in prognosis prediction and miRNA-based HCC therapy.

PMID- 23967870
TI  - Tranexamic acid accelerates skin barrier recovery and upregulates occludin in
      damaged skin.
AB  - BACKGROUND: Tranexamic acid (TA) is a traditional plasmin inhibitor, and its role
      in the renovation of damaged skin has become the topic of a lot of research. The
      aim of this study is to determine whether TA could repair the skin barrier by
      means of tight intercellular junctions. METHODS: Two kinds of damaged skin models
      were set up and subjected to repeated application of sodium lauryl sulfate and
      irradiation of ultraviolet B. Through bioengineering technology and
      immunohistochemistry tests, TA-induced changes in skin were detected. RESULTS:
      After 1, 3, 7, and 14 days of application, TA can significantly accelerate
      barrier recovery and decrease the melanin index values of ultraviolet B
      irritation skin. The mean optic density of occludin from TA treatment is higher
      than from self-repair. CONCLUSION: These experiments suggest that TA can
      accelerate skin barrier recovery and upregulate occludin induced by
      physicochemical damages of human skin, but it is advisable to perform more
      research on the upregulation of occludin in molecular mechanism in the future.

PMID- 23967871
TI  - Contributions of HIV-1 Nef to immune dysregulation in HIV-infected patients: a
      therapeutic target?
AB  - INTRODUCTION: HIV accessory protein Nef is a factor responsible for many of the
      viral pathogenic effects. Progression to AIDS is dramatically delayed and in some
      well-documented cases completely abolished on infection with naturally occurring
      HIV strains lacking intact nef sequences in their genomes. The topic of this
      review is the contribution of Nef to the immune pathology as a possible target in
      HIV-infected patients. AREAS COVERED: An overview of known Nef functions
      accounting for its role in pathogenesis is presented, emphasizing interactions
      with dendritic cells and macrophages, and Nef-induced exosome secretion, all
      involved in immune dysregulation during the course of HIV infection. Current
      approaches to Nef inhibition by different classes of compounds are reviewed.
      EXPERT OPINION: Blocking Nef for therapeutic purposes is a challenging endeavor
      mainly due to intrinsic properties of this HIV accessory protein. Nef has
      multiple interfaces to interact with host proteins and lacks a catalytic domain.
      Potential benefits arising from the development of successful inhibitors could
      however prove beneficial for reducing gradual deterioration of immune system in
      chronically infected patients in absence of functional cure.

PMID- 23967872
TI  - Four-electron oxidative dehydrogenation induced by proton-coupled electron
      transfer in ruthenium(III) complex with 2-(1,4,5,6-tetrahydropyrimidin-2
      yl)phenolate.
AB  - New ruthenium(II or III) complexes with general formula [Ru(O-N)(bpy)2](n+) (O-N
      = unsymmetrical bidentate phenolate ligand; bpy = 2,2'-bipyridine) were
      synthesized, and their crystal structures and electrochemical properties were
      characterized. Ru(II) complexes with 2-(2-imidazolinyl)phenolate (Himn(-)) or 2
      (1,4,5,6-tetrahydropyrimidin-2-yl)phenolate (Hthp(-)) could be deprotonated by
      addition of excess KO(t)Bu, although the deprotonated species were easily
      reprotonated by exposure to air. Unlike these Ru(II) complexes, their Ru(III)
      analogs showed interesting ligand oxidation reactions upon addition of bases.
      With [Ru(III)(Himn)(bpy)2](2+), two-electron oxidation of Himn(-) and reduction
      of the Ru(III) center resulted in conversion of the 2-imidazolinyl group to a 2
      imidazolyl group. On the other hand, the corresponding Hthp(-) complex exhibited
      four-electron oxidation of the ligand to form 2-(2-pyrimidyl)phenolate (pym(-)).
      These aromatization reactions of imidazolinyl and 1,4,5,6-tetrahydropyrimidyl
      groups were also achieved by the electrochemically generated Ru(III) complexes. 

PMID- 23967873
TI  - Prevalence of synchronous colorectal neoplasms in surgically treated gastric
      cancer patients and significance of screening colonoscopy.
AB  - BACKGROUND AND AIM: The existence of other primary tumors during the treatment
      and management of gastric cancer (GC) is an important issue. The present study
      investigated the prevalence and management of synchronous colorectal neoplasms
      (CRN) in surgically treated GC patients. METHODS: Of 381 surgically treated GC
      patients, 332 (87.1%) underwent colonoscopy to detect CRN before surgery or
      within a year after surgery. RESULTS: CRN were synchronously observed in 140
      patients (42.2%). Adenoma was observed in 131 patients (39.4%). Endoscopic
      resection was done in 18 patients with adenoma. Colorectal cancer (CRC) was
      observed in 16 patients (4.8%), superficial CRC in 13 and advanced CRC in three
      patients. Endoscopic resection of superficial CRC was carried out in seven
      patients, whereas simultaneous surgical resection of CRC was done in nine
      patients. CRN were more frequently observed in men. CRC was more frequently
      observed in GC patients with distant metastasis, albeit without significance. The
      overall survival of GC patients with CRN or CRC was poorer than that of patients
      without CRN or CRC. CONCLUSION: Synchronous CRN were commonly associated with GC
      and screening colonoscopy should be offered to patients with GC.

PMID- 23967875
TI  - A single-molecule magnet based on heptacyanomolybdate with the highest energy
      barrier for a cyanide compound.
AB  - Three trinuclear Mn2Mo molecules based on the orbitally degenerate [Mo(CN)7](4-)
      anion were prepared, one of which is the first single-molecule magnet (SMM) based
      on heptacyanomolybdate. The blocking temperature and the energy barrier (U = 40.5
      cm(-1)) are records for a cyanide-based SMM. Wide hysteresis loops and sharp
      quantum tunneling steps were observed from single-crystal measurements. 

PMID- 23967874
TI  - Formation and ecotoxicity of N-heterocyclic compounds on ammoxidation of mono-
      and polysaccharides.
AB  - Ammoxidation of technical lignins under mild conditions is a suitable approach to
      artificial humic substances. However, carbohydrates as common minor constituents
      of technical lignins have been demonstrated to be a potential source of N
      heterocyclic ecotoxic compounds. Ethyl acetate extracts of ammoxidation mixtures
      of the monosaccharides glucose and xylose exhibited considerable growth
      inhibiting activity in the OECD 201 test, with 4-methyl-1H-imidazole, 4
      (hydroxymethyl)-1H-imidazole, and 3-hydroxypyridine being the most active
      compounds. The amount of N-heterocyclic compounds formed at moderate ammoxidation
      conditions (70  degrees C, 0.2 MPa O2, 3 h) was significantly lower for the
      polysaccharides cellulose and xylan (16-30 MUg/g of educt) compared to glucose
      (15.4 mg). Ammoxidation at higher temperature is not recommendable for
      carbohydrate-rich materials as much higher amounts of N-heterocyclic compounds
      were formed from both monosaccharides (100  degrees C: 122.4-160.5 mg/g of educt)
      and polysaccharides (140  degrees C: 5.52-16.03 mg/g of educt). 

PMID- 23967876
TI  - Subjective sleep quality in relation to objective sleep estimates: comparison,
      gender differences and changes between the acute phase and the six-month follow
      up after stroke.
AB  - AIMS: To describe sleep experiences after stroke using subjective and objective
      indicators and identify possible gender differences in sleep in the acute phase
      and at 6-month follow-up. BACKGROUND: Sleep disturbances after stoke are
      recognized, but poorly described. Gender differences in sleep exist in other
      populations, but have not been reported after stroke. DESIGN: A longitudinal
      cohort study. METHOD: Subjective sleep quality was measured with the Pittsburgh
      Sleep Quality Index and objective sleep was estimated with actigraphy in 100
      patients in the acute phase and six months after stroke, from April 2007-March
      2009. FINDINGS: Subjective sleep quality was better and objective wake percentage
      was lower at follow-up than in the acute phase after stroke. Actigraphy estimated
      low sleep efficiency and many awakenings at both time points. Subjective and
      objective measures were correlated at the 6-month follow-up, but not in the acute
      phase. Women's subjective sleep efficiency and total score on the Pittsburgh
      Sleep Quality Index were worse than men's in the acute phase, but actigraphy
      estimated that women slept more than men in the course of a day. Women's
      subjective sleep quality was better at follow-up than in the acute phase. Men
      reported worse subjective sleep quality, but better subjective sleep efficiency
      at follow-up than in the acute phase, and also had lower objective wake
      percentage at follow-up. CONCLUSIONS: Subjective sleep quality was poor and
      actigraphy indicated disturbed sleep-wake patterns in the acute phase and at 6
      month follow-up. Gender differences existed in subjective and objective sleep in
      the acute phase, but not at follow-up.

PMID- 23967877
TI  - Cu-catalyzed cross-dehydrogenative coupling reactions of (benzo)thiazoles with
      cyclic ethers.
AB  - Copper-catalyzed cross-dehydrogenative coupling (CDC) reactions of
      (benzo)thiazoles with cyclic ethers were developed under mild conditions. In
      particular, the formation of C-C bonds via the CDC reactions between non-benzo
      fused azoles and ethers are reported for the first time. In addition, the
      acetals, known as the masked 2-thiazolecarboxaldehydes, could be successfully
      obtained by this CDC reaction. The preliminary mechanism and supportive DFT
      calculations are discussed as well. 

PMID- 23967878
TI  - Pain in chronic fatigue syndrome: response to rehabilitative treatments in the
      PACE trial.
AB  - BACKGROUND: Pain is a common symptom of chronic fatigue syndrome (CFS). We
      investigated the effects of the treatments used in the PACE trial [cognitive
      behavioural therapy (CBT), graded exercise therapy (GET), adaptive pacing therapy
      (APT) and specialist medical care (SMC)] on pain in CFS. METHOD: We compared pain
      outcomes including individual painful symptoms, taken from the CDC criteria for
      CFS and co-morbid fibromyalgia. We modelled outcomes adjusting for baseline
      variables with multiple linear regression. RESULTS: Significantly less frequent
      muscle pain was reported by patients following treatment with CBT compared to SMC
      (mean difference = 0.38 unit change in frequency, p = 0.02), GET versus SMC
      (0.42, p = 0.01) and GET versus APT (0.37, p = 0.01). Significantly less joint
      pain was reported following CBT versus APT (0.35, p = 0.02) and GET versus APT
      (0.36, p = 0.02). Co-morbid fibromyalgia was less frequent following GET versus
      SMC (0.03, p = 0.03). The effect sizes of these differences varied between 0.25
      and 0.31 for muscle pain and 0.24 and 0.26 for joint pain. Treatment effects on
      pain were independent of 'change in fatigue'. CONCLUSIONS: CBT and GET were more
      effective in reducing the frequency of both muscle and joint pain than APT and
      SMC. When compared to SMC, GET also reduced the frequency of co-morbid
      fibromyalgia; the size of this effect on pain was small.

PMID- 23967879
TI  - Hashimoto's encephalopathy: four cases and review of literature.
AB  - Hashimoto's encephalopathy is a rare clinically heterogenous condition consisting
      of encephalopathy, seizures and variable neurological and psychiatric
      manifestations, accompanied by high titres of serum antithyroid antibodies. We
      described the clinical and laboratory findings of four children (aged 8-17 years)
      with Hashimoto's encephalopathy. The clinical features of three patients at
      presentation included refractory epilepsy, and confusion, and one patient
      presented with behavioral and cognitive changes. During their presentation, two
      of them were in euthyroid, and the others were in hypothyroid status. All
      patients manifested increased antithyroid antibodies. Two patients improved with
      steroid treatment. The others responded to plasmapheresis instead of
      corticosteroid treatment. Physicians' awareness of this complication is of great
      importance because most patients respond dramatically to the treatment.

PMID- 23967880
TI  - Demographic and clinical features of 521 Turkish patients with Behcet's disease.
AB  - BACKGROUND: The aim of this study is to reveal demographic and clinical features
      of Behcet's disease (BD) in a Turkish population. METHODS: We retrospectively
      evaluated the clinical findings of 521 patients with BD. RESULTS: A total of 521
      patients (287 female and 234 male) were included in this study. Onset signs: oral
      ulceration (72.7%) was followed by genital ulceration (3.1%), ocular involvement
      (1.0%), and erythema nodosum-like lesions (ENLL) (0.2%). In 120 patients (23%),
      the onset manifestation compromised more than one symptom. During follow-up, in
      females and males respectively, oral ulceration was found in 100%, genital
      ulceration in 90.9% and in 82.5%, papulopustular lesions in 52.6% and in 71.4%,
      positive pathergy test in 45.3% and in 48.7%, ENLL in 43.6% and in 31.6%, ocular
      involvement in 36.9% and in 58.1%, gastrointestinal involvement in 6.6% and in
      5.6%, joint involvement in 4.2% and in 6.4%, vascular involvement in 1.7% and in
      10.6%, neurological involvement in 0% and in 4.7% and pulmonary involvement in
      0.7% and in 0.7%. Genital ulceration and ENLL were found to be statistically
      higher in females than males. Papulopustular lesions and ocular, neurological,
      and vascular involvement were significantly higher in males than females.
      CONCLUSIONS: In our study, systemic involvement was higher in males than females,
      as the disease is more severe in males than females. As the only initial finding
      of the disease can be genital ulceration or ocular manifestations, gynecologists,
      urologists, ophthalmologists, and family practitioners must keep in mind BD as a
      differential diagnosis.

PMID- 23967881
TI  - Patterns and expenditures of multi-morbidity in an insured working population in
      the United States: insights for a sustainable health care system and building
      healthier lives.
AB  - The U.S. health care system is currently heading toward unsustainable health care
      expenditures and increased dissatisfaction with health outcomes. The objective of
      this population-based study is to uncover practical insights regarding patients
      with 1 or more chronic illnesses. A cross-sectional investigation was designed to
      gather data from health records drawn from diverse US geographic markets. A
      database of 9.74 million fully-insured, working individuals was used, together
      with members in the same households. Among nearly 3.43 million patients with
      claims, 2.22 million had chronic conditions. About 24.3% had 1 chronic condition
      and 40.4% had multi-morbidity. Health care expenditures for chronic conditions
      accounted for 92% of all costs (52% for chronic costs and 40% for nonchronic
      costs). Psychiatry, orthopedics-rheumatology, endocrinology, and cardiology areas
      accounted for two thirds of these chronic condition costs; nonchronic condition
      costs were dominated by otolaryngology, gastroenterology, dermatology,
      orthopedics-rheumatology conditions, and preventive services. About 50.1% of all
      households had 2 or more members with chronic conditions. In summary, multi
      morbidity is prevalent not only among those older than age 65 years but also in
      younger and working individuals, and commonly occurs among several members of a
      household. The authors suggest that the disease-focused model of medicine should
      change to a more holistic illness-wellness model, emphasizing not only the
      physical but also the mental and social elements that can influence individual
      health. In that way the chronic care model could be broadened in context and
      content to improve the health of patients and households.

PMID- 23967882
TI  - Examining tobacco outlet concentration in New Jersey: does income and ethnicity
      matter?
AB  - This study examined the geographic association between tobacco outlet density and
      the demographic indicators of median household income and percentage of Hispanic
      residents in New Jersey. Tobacco outlet density was assessed by examining all
      tobacco retailers licensed in 2004 in New Jersey, and demographic variables were
      based on the 2000 United States Census. Results indicated that the percentage of
      Hispanic residents and median household income were both salient predictors of
      tobacco outlet density. We also observed that income level moderated the
      relationship between the percentage of Hispanics residents and tobacco outlet
      density. Implications for environmentally based tobacco prevention and control
      initiatives are discussed. 

PMID- 23967883
TI  - Substance abuse and mental health issues within Native American grandparenting
      families.
AB  - Substance abuse and mental health problems among Native Americans are associated
      with a variety of general health, social, and economic problems. This current
      study examined Native American grandparents who are raising their grandchildren
      and found that a child, parent, or grandparent had an alcohol or drug problem in
      36% of families. Substance abuse on the part of a parent was correlated with the
      reasons grandparents were raising their grandchildren. Native American
      grandparents raising grandchildren cope with a variety of challenges and receive
      little state-funded assistance or help from others. 

PMID- 23967884
TI  - Ethnic and gender differences in normative perceptions of substance use and
      actual use among college students.
AB  - The primary objective of this study was to examine whether perceived norms about
      cigarette, alcohol, and marijuana use differed from actual use by ethnicity using
      data from the 2011 College Health Survey (N = 974). Analyses of covariance
      controlling for year in college and sorority or fraternity membership indicated a
      higher mean discrepancy scores for all substances for minority students compared
      with White students. Results suggest that minorities may be at an increased risk
      for substance use due to their perception that the typical student is using more
      than they actually are. An implication is that social marketing messages may need
      to be tailored to recognize these discrepancies. 

PMID- 23967885
TI  - Protective behavioral strategies, alcohol consumption, and negative alcohol
      related consequences: do race and gender moderate these associations?
AB  - White, non-Hispanic college students tend to drink more alcohol and experience
      more negative consequences than African American college students. However,
      racial differences have not been examined for protective behavioral strategies.
      This study examined whether race and gender moderated the associations that
      protective behavioral strategies had with alcohol consumption and negative
      alcohol-related consequences. In general, the use of protective behavioral
      strategies were associated with greater deceases in consumption, harmful
      drinking, and negative consequences for White, non-Hispanic students than African
      American students, which suggests important racial differences related to
      protective strategy use. Research and clinical implications are provided. 

PMID- 23967886
TI  - Underage drinking among Asian American and Pacific Islander adolescents.
AB  - This study assessed the prevalence of alcohol abuse and dependence rates among
      four major ethnic groups of Hawai'i and examined the relationship among risk
      factors, protective factors, and demographic variables related to underage
      drinking. A total of 196 students were administered the Diagnostic Interview
      Schedule for Children, the American Drug and Alcohol Survey, and the Prevention
      Planning Survey. Drinking rates for Native Hawaiian students were significantly
      higher than those for Japanese and Caucasian students. Multiple logistic
      regression models accounted for 49% of the variance for any alcohol use. Ethnic
      group differences were found when data were disaggregated for Asian and Pacific
      Islander students. 

PMID- 23967887
TI  - A neuroethological framework for the representation of minds.
AB  - The cognition that constructs mental features such as intention, disposition, and
      character is an aspect of theory of mind. This aspect of representation of minds,
      which inherently has valence, is viewed from cognitive, evolutionary, and neural
      perspectives. It is proposed that this cognition is modular, and that it normally
      operates in association with a valence-free cognition able to represent mental
      states such as belief. Examples of neural activity capable of supporting the
      social representations macaque monkeys are believed to possess (understanding of
      affective displays, purposeful movement, and elemental social interactions) are
      presented. 

PMID- 23967888
TI  - Preserved visual imagery and categorization in a case of associative visual
      agnosia.
AB  - A patient with associative visual agnosia secondary to a penetrating
      bitemporooccipital lesion remained able to draw complex objects from memory but
      could not subsequently recognize his sketches. His retained ability to copy and
      draw briefly exposed objects indicates that this is not a problem of visual
      perception. On tasks of categorization, mental imagery, drawing, and object
      decision, he demonstrates many instances of preserved visual semantic memories
      and imagery despite a sense of unfamiliarity with the visual stimuli. We infer a
      preserved ability to derive internal visual images from semantic memory. Cues may
      help him visualize the named object, which then serves as a model for comparison
      with the actual stimulus. However, his adequate visual perception and mental
      visual imagery, even when assisted by cues, are still insufficient to correct
      fully his difficulty in recognizing objects. Unique to his case is an inability
      to match the representation of stimulus objects with his intact internal image of
      the same object. Deficient lateral inhibition between neural representations of
      similar objects may be responsible. 

PMID- 23967889
TI  - An Event-Related Potential (ERP) Analysis of Semantic Congruity and Repetition
      Effects in Sentences.
AB  - In two experiments, event-related brain potentials (ERPs) and cued-recall
      performance measures were used to examine the consequences of semantic congruity
      and repetition on the processing of words in sentences. A set of sentences, half
      of which ended with words that rendered them semantically incongruous, was
      repeated either once (eg, Experiment 1) or twice (e.g., Experiment 2). After each
      block of sentences, subjects were given all of the sentences and asked to recall
      the missing final words. Repetition benefited the recall of both congruous and
      incongruous endings and reduced the amplitude and shortened the duration of the
      N400 component of the ERP more for (1) incongruous than congruous words, (2) open
      class than closed class words, and (3) low-frequency than high-frequency open
      class words. For incongruous sentence terminations, repetition increased the
      amplitude of a broad positive component subsequent to the N400. Assuming additive
      factors logic and a traditional view of the lexicon, our N400 results indicate
      that in addition to their singular effects, semantic congruiry, repetition, and
      word frequency converge to influence a common stage of lexical processing. Within
      a parallel distributed processing framework, our results argue for substantial
      temporal and spatial overlap in the activation of codes subserving word
      recognition so as to yield the observed interactions of repetition with semantic
      congruity, lexical class, and word frequency effects. 

PMID- 23967890
TI  - Savings in relearning face-name associations as evidence for "covert recognition"
      in prosopagnosia.
AB  - Prosopagnosic patients appear to be impaired at recognizing faces. However,
      recent evidence for "covert recognition" in prosopagnosia has been taken to
      suggest that the impairment is not in face recognition per se, but rather in
      conscious access to face recognition. The most widely used test for covert
      recognition of faces in prosopagnosia is the face-name relearning task, in which
      some prosopagnosics have been found to learn correct names for previously
      familiar faces more easily than incorrect names. Although this phenomenon is
      consistent with face recognition operating normally but out of reach of conscious
      awareness, it may also be consistent with an impairment in face recognition per
      se. Perhaps savings in relearning is sufficiently sensitive to the residual
      information contained in degraded face representations that are not detectable by
      overt measures of recognition. If so, then we should expect to observe this same
      savings in relearning when overt recognition is obliterated for reasons other
      than brain damage. In the present study, we used forgetting of face-name
      associations in normal subjects as a way of degrading recognition ability. We
      found the same dissociation between overt recognition performance and savings in
      relearning as observed in prosopagnosic patients. This implies that the
      performance of prosopagnosic patients in these tasks does not demand explanation
      in terms other than an impairment in face recognition per se. 

PMID- 23967891
TI  - Modes of lexical access in the callosotomized brain.
AB  - Left hemisphere processing is typically characterized as analytic and serial
      whereas the right hemisphere is characterized as wholistic and parallel. Word
      recognition may be an exception to this dichotomy if the letter-by-letter alexia
      produced by left hemisphere damage reflects the reading abilities of the right
      hemisphere. We investigated this possibility by studying prelexical and lexical
      processes in the separated hemispheres of callosotomy patient J. W. A word
      superiority effect demonstrated in each visual field suggests that both
      hemispheres have access to a visual lexicon. Error patterns, letter recognition
      thresholds, and lexical decision performance as a function of word length suggest
      that the left hemisphere tends to utilize a parallel access mode, whereas the
      right hemisphere mode is less efficient and may be serial. Furthermore, only J.
      W.'s left hemisphere showed letter priming, an outcome consistent with
      observations in letter-by-letter alexia. These findings suggest that the right
      hemisphere may have an independent visual lexicon and may provide an alternative
      although less efficient route to reading. We suggest that a serial encoding
      strategy results because the global processing mode for which the right
      hemisphere is specialized is largely ineffective for word reading. 

PMID- 23967893
TI  - Neocortical development.

PMID- 23967892
TI  - Effects of multiple stimuli on ocular orientation by cats.
AB  - We investigated the characteristics of saccades made by cats in response to
      single and double stimuli. Stimuli were either visual, auditory, or bimodal. We
      initially trained cats to look toward the location of briefly presented single
      visual or single auditory targets that were extinguished before the initiation of
      eye movements. Following training, we monitored eye movements during and after
      the presentation of double targets, either two visual, two auditory, or bimodal,
      that were at disparate spatial locations. Cats made saccadic eye movements to
      positions that ranged between the location of the two targets. If the eye
      position at the start of a saccade was near the mid point of the targets, cats
      were less likely to initiate a saccade, and saccadic latencies were longer,
      compared to when starting eye position was at a distance from this location.
      These behavioral results are consistent with the hypothesis that the neural
      representations of briefly presented targets are combined and treated as a
      unitary, low resolution stimulus from which an orienting motor program is
      derived. The similarity of responses to double visual, double auditory, and
      bimodal stimuli suggests that a common sensorimotor mechanism applies within and
      between these sensory modalities. 

PMID- 23967894
TI  - Plasticity of development.

PMID- 23967895
TI  - Study protocol: precision of a protocol for manual intramuscular needle placement
      checked by passive stretching and relaxing of the target muscle in the lower
      extremity during BTX-A treatment in children with spastic cerebral palsy, as
      verified by means of electrical stimulation.
AB  - BACKGROUND: Intramuscular injection of botulinum toxin type-A given by manual
      intramuscular needle placement in the lower extremity under general anaesthesia
      is an established treatment and standard of care in managing spasticity in
      children with spastic cerebral palsy. Optimal needle placement is essential.
      However, reports of injection and verification techniques used in previous
      studies have been partly incomplete and there are methodological shortcomings.
      This paper describes a detailed protocol for manual intramuscular needle
      placement checked by passive stretching and relaxing of the target muscle for
      each individual muscle injection location in the lower extremity during botulinum
      toxin type-A treatment under general anaesthesia in children with spastic
      cerebral palsy. It explains the design of a study to verify this protocol, which
      consists of an injection technique combined with a needle localizing technique,
      as by means of electrical stimulation to determine its precision. METHODS: 
      SETTING: University Medical Centre, Department of Paediatric Rehabilitation
      Medicine, the Netherlands. DESIGN: prospective observational study. PARTICIPANTS:
      children with spastic cerebral palsy, aged 4 to 18 years, receiving regular
      botulinum toxin type-A treatment under general anaesthesia to improve their
      mobility, are recruited from the Department of Paediatric Rehabilitation Medicine
      at VU University Medical Centre, Amsterdam, the Netherlands. METHOD: a detailed
      protocol for manual intramuscular needle placement checked by passive stretching
      and relaxing of the target muscle has been developed for each individual muscle
      injection location of the adductor brevis muscle, adductor longus muscle,
      gracilis muscle, semimembranosus muscle, semitendinosus muscle, biceps femoris
      muscle, rectus femoris muscle, gastrocnemius lateralis muscle, gastrocnemius
      medialis muscle and soleus muscle. This protocol will be verified as by means of
      electrical stimulation.Technical details: 25 mm or 50 mm Stimuplex-needle and a
      Stimuplex-HNS-12 electrical stimulator will be used. DISCUSSION: Botulinum toxin
      type-A injected in the intended muscle is expected to yield the greatest effect
      in terms of activities. Protocols for manual intramuscular needle placement
      should be described in detail and verified to determine its precision. Detailed
      and verified protocols are essential to be able to interpret the results of
      botulinum toxin type-A treatment studies.

PMID- 23967896
TI  - Strategies to assess the validity of recommendations: a study protocol.
AB  - BACKGROUND: Clinical practice guidelines (CPGs) become quickly outdated and
      require a periodic reassessment of evidence research to maintain their validity.
      However, there is little research about this topic. Our project will provide
      evidence for some of the most pressing questions in this field: 1) what is the
      average time for recommendations to become out of date?; 2) what is the
      comparative performance of two restricted search strategies to evaluate the need
      to update recommendations?; and 3) what is the feasibility of a more regular
      monitoring and updating strategy compared to usual practice?. In this protocol we
      will focus on questions one and two. METHODS: The CPG Development Programme of
      the Spanish Ministry of Health developed 14 CPGs between 2008 and 2009. We will
      stratify guidelines by topic and by publication year, and include one CPG by
      strata.We will develop a strategy to assess the validity of CPG recommendations,
      which includes a baseline survey of clinical experts, an update of the original
      exhaustive literature searches, the identification of key references (reference
      that trigger a potential recommendation update), and the assessment of the
      potential changes in each recommendation.We will run two alternative search
      strategies to efficiently identify important new evidence: 1) PLUS search based
      in McMaster Premium LiteratUre Service (PLUS) database; and 2) a Restrictive
      Search (ReSe) based on the least number of MeSH terms and free text words needed
      to locate all the references of each original recommendation.We will perform a
      survival analysis of recommendations using the Kaplan-Meier method and we will
      use the log-rank test to analyse differences between survival curves according to
      the topic, the purpose, the strength of recommendations and the turnover. We will
      retrieve key references from the exhaustive search and evaluate their presence in
      the PLUS and ReSe search results. DISCUSSION: Our project, using a highly
      structured and transparent methodology, will provide guidance of when
      recommendations are likely to be at risk of being out of date. We will also
      assess two novel restrictive search strategies which could reduce the workload
      without compromising rigour when CPGs developers check for the need of updating.

PMID- 23967897
TI  - Effects of betaine on body composition, performance, and homocysteine
      thiolactone.
AB  - BACKGROUND: This study investigated the effects of long term betaine
      supplementation on body composition, performance, and homocysteine thiolactone
      (HCTL) in experienced strength trained men. METHODS: Twenty-three subjects were
      matched for training experience (4.8 +/- 2.3 years) and body fat percentage (BF%:
      16.9 +/- 8.0%), randomly assigned to either a placebo (PL; n = 12) or betaine
      group (BET; n = 11; 2.5 g/day), and completed a 6 week periodized training
      program consisting of 3 two-week micro-cycles. Bench press and back squat
      training volumes were recorded and changes in training volume were assessed at
      each micro-cycle. Fasting urine was collected at baseline (BL), weeks 2, 4 and 6,
      and assayed for HCTL. Subjects were tested prior to and following 6 weeks of
      treatment. Arm and thigh cross sectional area (CSA) was estimated via girth and
      skin fold measurements. Body density was estimated via skin fold calipers and
      used to estimate BF%, fat mass (FM), and lean body mass (LBM). Performance was
      assessed via vertical jump (VJ), bench press 1 RM (BP), and back squat 1 RM (BS).
      RESULTS: Arm CSA increased significantly (p < .05) in BET but not PL. No
      differences existed between group and time for changes in thigh CSA. Back squat
      training volume increased significantly (p < .05) for both groups throughout
      training. Bench press training volume was significantly (p < .05) improved for
      BET compared to PL at microcycles one and three. Body composition (BF%, FM, LBM)
      improved significantly (p < .05) in BET but not PL. No differences were found in
      performance variables (BP, BS, VJ) between groups, except there was a trend (p =
      .07) for increased VJ power in BET versus PL. A significant interaction (p < .05)
      existed for HCTL, with increases from BL to week 2 in PL, but not BET.
      Additionally, HCTL remained elevated at week 4 in PL, but not BET. CONCLUSION:
      Six-weeks of betaine supplementation improved body composition, arm size, bench
      press work capacity, attenuated the rise in urinary HCTL, and tended to improve
      power (p = .07) but not strength.

PMID- 23967898
TI  - Drug reaction with eosinophilia and systemic symptoms syndrome caused by an
      everolimus-eluting stent.

PMID- 23967899
TI  - Microsomal oxidative stress induced by NADPH is inhibited by nitrofurantoin redox
      biotranformation.
AB  - Nitrofurantoin is used in the antibacterial therapy of the urinary tract. This
      therapy is associated with various adverse effects whose mechanisms remain
      unclear. Diverse studies show that the nitro reductive metabolism of
      nitrofurantoin leads to ROS generation. This reaction can be catalyzed by several
      reductases, including the cytochrome P450 (CYP450) reductase. Oxidative stress
      arising from this nitro reductive metabolism has been proposed as the mechanism
      underlying the adverse effects associated with nitrofurantoin. There is, however,
      an apparent paradox between these findings and the ability of nitrofurantoin to
      inhibit lipid peroxidation provoked by NADPH in rat liver microsomes. This work
      was aimed to show the potential contribution of different enzymatic systems to
      the metabolism of this drug in rat liver microsomes. Our results show that
      microsomal lipid peroxidation promoted by NADPH is inhibited by nitrofurantoin in
      a concentration-dependent manner. This suggests that the consumption of NADPH in
      microsomes can be competitively promoted by lipid peroxidation and nitrofurantoin
      metabolism. The incubation of microsomes with NADPH and nitrofurantoin generated
      1-aminohidantoin. In addition, the biotransformation of a classical substrate of
      CYP450 oxidative system was competitively inhibited by nitrofurantoin. These
      results suggest that nitrofurantoin is metabolized through CYP450 system. Data
      are discussed in terms of the in vitro redox metabolism of nitrofurantoin.

PMID- 23967900
TI  - The burden of headache disorders in Pakistan: methodology of a population-based
      nationwide study, and questionnaire validation.
AB  - BACKGROUND: Large geographical gaps in our knowledge of the prevalence and burden
      of headache disorders include Pakistan, a country with major problems of poverty,
      illiteracy and security. We report implementation in this country of standard
      methods developed by Lifting The Burden (LTB) for population-based burden-of
      headache studies. METHODS: We surveyed six locations from the four provinces:
      Lahore and Multan (Punjab), Karachi and Sukkur (Sindh), Abbottabad (Khyber
      Pakhtunkhwa) and Gwadar (Baluchistan). We randomly selected rural and urban
      households in each, which were visited by trained non-medical interviewers from
      the same locations. One randomly selected adult member (18-65 years) of each
      household was interviewed using LTB's structured questionnaire translated into
      Urdu, the national language. Validation was performed among patients and
      accompanying attendants in three (urban and rural) medical facilities. After
      responding to the questionnaire, these participants were re-interviewed and
      diagnosed by a neurologist (gold standard). RESULTS: The survey was completed by
      4,223 respondents (1,957 [46.3%] male, 2,266 [53.7%] female, 1,443 [34.2%] urban,
      2,780 [65.8%] rural, mean age 34.4 +/- 11.0 years). The participation rate was
      89.5%. There were 180 participants (46.1% male, 53.9% female, 41.7% urban, 58.3%
      rural, mean age 39.4 +/- 14.2 years) in the validation sample, of whom 147
      (81.7%) reported headache in the last year. The questionnaire was 100% sensitive
      in screening for headache and for headache on >=15 days/month, and showed good
      agreement with the gold-standard diagnoses (kappa = 0.77). It was relatively
      insensitive for TTH. The questionnaire's default diagnosis of probable MOH when
      medication overuse accompanied headache on >=15 days/month was not supported by
      evidence of causation in most cases seen by the neurologist. In public-health
      terms, precise diagnosis in these cases matters less than reliably detecting the
      coexistence of these disorders. CONCLUSION: In conclusion, the methods developed
      by LTB were applied successfully in Pakistan, despite problems unique to this
      country.

PMID- 23967901
TI  - Development and validation of the Work Stressor Inventory for Nurses in Oncology:
      preliminary findings.
AB  - AIM: This study is a report of the development and testing of the Work Stressor
      Inventory for Nurses in Oncology. BACKGROUND: Stressors in oncology nursing are
      generally assessed using generic stress scales like the Nursing Stress Scale or
      the Health Professions Stress Inventory. However, qualitative investigations have
      highlighted the specific nature of the stress to which nurses are exposed.
      DESIGN: The Work Stressor Inventory for Nurses in Oncology was developed using
      both qualitative and quantitative methodologies. METHOD: For the item generation
      phase, a semi-structured interview was conducted with 59 nurses working in
      oncology units during 2007. A total of 51 work-related items were retained for
      the final survey. A convenience sample of 582 nurses working in oncology
      completed the survey between January 2008-June 2008. They also completed the
      General Health Questionnaire and the Maslach Burnout Inventory. The Work Stressor
      Inventory for Nurses in Oncology was further tested for theoretically supported
      constructs, internal consistency reliability and concurrent validity. FINDINGS:
      The exploratory results revealed five factors: workload, dealing with death and
      dying, dealing with suffering, interpersonal conflicts, dealing with patients and
      relatives. The internal consistency of the five subscales was satisfactory.
      Correlation patterns between the Work Stressor Inventory for Nurses in Oncology
      dimensions and both mental health and burnout variables support the criterion
      related validity of the scale. CONCLUSION: Future quantitative or qualitative
      studies using this scale could add knowledge about the experiences of emotional
      and organizational stressors related to this area of nursing.

PMID- 23967902
TI  - Effect of electrostatic and size on dopant occupancy in lithium niobate single
      crystal.
AB  - We proposed a simple and an effective method to predict the site occupancy and
      threshold concentration of metal ions in lithium niobate (LiNbO3, LN) single
      crystal. The ionic energy parameter E(i), defined by the ionic electronegativity
      and ionic radius, was proposed to describe the electrostatic and size effects of
      cations on the structural stability of LN. The dopant location can be easily
      identified by comparing the E(i) deviation of dopant from those of host cations
      Li(+) and Nb(5+), and the dopant prefers to occupy the lattice site with the
      smaller deviation of E(i). Our calculated occupancies agree well with those
      experimental results, which demonstrate the predictive power of our present
      method. We in this work predicted the preferred occupancies of 60 metal ions in
      LN single crystal. Further, the threshold concentrations of some frequently used
      dopants were calculated on the basis of the assumption that all doped LN crystals
      can endure the same variation of E(i).

PMID- 23967903
TI  - Surveillance of human influenza A(H3N2) virus from 1999 to 2009 in southern
      Italy.
AB  - The aim of this study was to evaluate the presence of influenza virus co
      infections in humans and changes in the genetic variability of A(H3N2) virus
      strains in southern Italy from 1999 to 2009. A partial sequence of the
      haemagglutinin (HA) gene by human influenza H3N2 strains identified in
      oropharyngeal swabs from patients with influenza-like illness was analysed by DNA
      sequencing and a phylogenetic analysis was performed. During the seasons 1999
      2000, 2002-2003, 2004-2005 and 2008-2009, the influenza viruses circulating
      belonged to subtype H3N2. However, A(H1N1) subtype virus and B type were
      respectively prevalent during the 2000-2001, 2006-2007, 2007-2008 and 2001-2002,
      2003-2004, 2005-2006 seasons. The HA sequences appeared to be closely related to
      the sequence of the influenza A vaccine strain. Only the 2002-2003 season was
      characterized by co-circulation of two viral lineages: A/New York/55/01(H3N2)
      like virus of the previous season and A/Fujian/411/02(H3N2)-like virus, a new H3
      variant. In this study, over the decade analysed, no significant change was seen
      in the sequences of the HA gene of H3 viruses isolated.

PMID- 23967904
TI  - Reaction field analysis and lipid bilayer location for lipophilic fluorophores.
AB  - Environment polarity can cause changes in absorbance or emission maxima, for a
      given fluorophore. This is termed solvatochromism. In this study semiempirical
      models of solvatochromic shifts are used to predict their lipid bilayer location.
      Four reaction field models are analyzed and compared, to provide the most
      accurate prediction of fluorophore solvatochromic shifts using a modified version
      of the Lippert equation. For curcumin, the reaction field of Block and Walker
      gave the strongest agreement between experimental and predicted values (r =
      0.978, p < 0.0001). For aluminum phthalocyanine disulfonic acid (AlPcS2), the
      reaction field of Wertheim, based on statistical mechanics, gave the best
      agreement (r = 0.951, p = 0.001) only when dispersion forces and solute
      polarizability are considered. The results of these models are correlated to the
      Dimroth-Reichardt ET(30) solvent polarity scale used by Frimer and colleagues.
      Using the model predicted values, curcumin is estimated to be 1-1.2 nm from the
      phospholipid-water interface, in the acyl chain region of the lipid bilayer.
      AlPcS2 is predicted to be 0.7-0.9 nm from the interface, at the fatty acid
      carbonyl. This investigation provides semiempirical methods to efficiently link
      fluorophore solvatochromic shifts to a location in the lipid bilayer via reaction
      field models. 

PMID- 23967905
TI  - Ammoxidation of lignocellulosic materials: formation of nonheterocyclic
      nitrogenous compounds from monosaccharides.
AB  - Ammoxidized technical lignins are valuable soil-improving materials that share
      many similarities with native terrestrial humic substances. In contrast to
      lignins, the chemical fate of carbohydrates as typical minor constituents of
      technical lignins during the ammoxidation processes has not been thoroughly
      investigated. Recently, we reported the formation of N-heterocyclic, ecotoxic
      compounds (OECD test 201) from both monosaccharides (D-glucose, D-xylose) and
      polysaccharides (cellulose, xylan) under ammoxidation conditions and showed that
      monosaccharides are a source more critical than polysaccharides in this respect.
      GC/MS-derivatization analysis of the crude product mixtures revealed that
      ammoxidation of carbohydrates which resembles the conditions encountered in
      nonenzymatical browning of foodstuff affords also a multitude of nonheterocyclic
      nitrogenous compounds such as aminosugars, glycosylamines, ammonium salts of
      aldonic, deoxyaldonic, oxalic and carbaminic acids, urea, acetamide, alpha
      hydroxyamides, and even minor amounts of alpha-amino acids. D-glucose and D
      xylose afforded largely similar product patterns which differed from each other
      only for those products that were formed under preservation of the chain
      integrity and stereoconfiguration of the respective monosaccharide. The kinetics
      and reaction pathways involved in the formation of the different classes of
      nitrogenous compounds under ammoxidation conditions are discussed.

PMID- 23967906
TI  - Pedunculated vascular anomaly of the distal duodenum treated by endoscopic
      polypectomy.

PMID- 23967907
TI  - Reciprocity in the scattering coefficients of acoustic waveguide modes.
AB  - In this Letter, a proof is provided for the reciprocity between modal scattering
      coefficients of the acoustic waveguides connected by a junction enclosure. The
      result holds for all waveguide modes and for junction enclosures with locally
      reactive boundary conditions away from the interfaces between the junction and
      waveguides. Also provided is a physical interpretation of the reciprocity of the
      modal scattering coefficients. The scattering of two-dimensional waveguide modes
      by a right-angled bend in a rectangular duct is used as an illustrating example. 

PMID- 23967908
TI  - Parametric head-related transfer function modeling and interpolation for cost
      efficient binaural sound applications.
AB  - Parametric methods for modeling the perceptually relevant features of head
      related transfer functions (HRTFs) are very important for the development of low
      cost immersive sound applications. This letter describes an efficient method
      based on a low-order infinite impulse response filter implemented by a chain of
      second order sections of conventional shelving and peak audio filters. The
      parameters (central frequency, gain, and quality factor) are numerically adjusted
      by iteratively fitting the frequency response of the filter to the desired HRTF.
      Besides allowing for low-order binaural models, the proposed approach provides an
      efficient way to synthesize HRTFs for non-measured angles by applying a simple
      interpolation between the parameters from neighboring responses. Additionally,
      the HRTF database size is significantly reduced. 

PMID- 23967909
TI  - Calculating the spectrum of anisotropic waveguides using a spectral method.
AB  - The computation of the spectrum of a waveguide with arbitrary anisotropy with
      spatial dependence is a challenging task due to the coupling between axial and
      azimuthal harmonics. This problem is tackled in cylindrical coordinates by
      extending a spectral method for the general case. By considering the matrix
      representation of the operator on the right-hand side of the governing equations,
      the latter are exactly reformulated as an infinite set of integro-differential
      equations. Essential part of this study is taking into account the coupling of
      different harmonics, which becomes evident from the kernels of these equations.
      Provided a waveguide is translationally invariant in the axial direction, the
      coupling of axial harmonics vanishes. A practical approximation and truncation
      procedure yields a generalized eigenvalue problem, which can be solved
      numerically to obtain the entire spectrum of the operator and to construct the
      dispersion curves for the eigenmodes. The spectral method is tested against the
      results from the measurements of dispersion curves for the monopole, dipole, and
      quadrupole normal modes of scaled boreholes in tilted transverse isotropy
      anisotropic rock sample. Besides, the comparison of dispersion curves calculated
      by the spectral method and those computed from the synthetic data is discussed. 

PMID- 23967910
TI  - Control of the stop band of an acoustic double fishnet.
AB  - The acoustic transmittance of two closely spaced solid plates, each perforated
      with a square array of cylindrical holes, exhibits a band of near-perfect
      acoustic attenuation originating from hybridization between a resonance in the
      gap separating the plates and pipe resonances in the holes. Displacement of one
      plate relative to the other, such that the holes are no longer aligned, or an
      increase in the plate separation leads to an increased center frequency of the
      stop band. This ability to easily tune the frequency of the stop band may prove
      advantageous. 

PMID- 23967911
TI  - Finite-size effects on the quasistatic displacement pulse in a solid specimen
      with quadratic nonlinearity.
AB  - There is an unresolved debate in the scientific community about the shape of the
      quasistatic displacement pulse produced by nonlinear acoustic wave propagation in
      an elastic solid with quadratic nonlinearity. Early analytical and experimental
      studies suggested that the quasistatic pulse exhibits a right-triangular shape
      with the peak displacement of the leading edge being proportional to the length
      of the tone burst. In contrast, more recent theoretical, analytical, numerical,
      and experimental studies suggested that the quasistatic displacement pulse has a
      flat-top shape where the peak displacement is proportional to the propagation
      distance. This study presents rigorous mathematical analyses and numerical
      simulations of the quasistatic displacement pulse. In the case of semi-infinite
      solids, it is confirmed that the time-domain shape of the quasistatic pulse
      generated by a longitudinal plane wave is not a right-angle triangle. In the case
      of finite-size solids, the finite axial dimension of the specimen cannot simply
      be modeled with a linear reflection coefficient that neglects the nonlinear
      interaction between the combined incident and reflected fields. More profoundly,
      the quasistatic pulse generated by a transducer of finite aperture suffers more
      severe divergence than both the fundamental and second order harmonic pulses
      generated by the same transducer. 

PMID- 23967912
TI  - Unmitigated numerical solution to the diffraction term in the parabolic nonlinear
      ultrasound wave equation.
AB  - Various numerical algorithms have been developed to solve the Khokhlov-Kuznetsov
      Zabolotskaya (KZK) parabolic nonlinear wave equation. In this work, a generalized
      time-domain numerical algorithm is proposed to solve the diffraction term of the
      KZK equation. This algorithm solves the transverse Laplacian operator of the KZK
      equation in three-dimensional (3D) Cartesian coordinates using a finite
      difference method based on the five-point implicit backward finite difference and
      the five-point Crank-Nicolson finite difference discretization techniques. This
      leads to a more uniform discretization of the Laplacian operator which in turn
      results in fewer calculation gridding nodes without compromising accuracy in the
      diffraction term. In addition, a new empirical algorithm based on the LU
      decomposition technique is proposed to solve the system of linear equations
      obtained from this discretization. The proposed empirical algorithm improves the
      calculation speed and memory usage, while the order of computational complexity
      remains linear in calculation of the diffraction term in the KZK equation. For
      evaluating the accuracy of the proposed algorithm, two previously published
      algorithms are used as comparison references: the conventional 2D Texas code and
      its generalization for 3D geometries. The results show that the
      accuracy/efficiency performance of the proposed algorithm is comparable with the
      established time-domain methods. 

PMID- 23967913
TI  - Fast acoustic streaming in standing waves: generation of an additional outer
      streaming cell.
AB  - Rayleigh streaming in a cylindrical acoustic standing waveguide is studied both
      experimentally and numerically for nonlinear Reynolds numbers from 1 to 30
      [Re(NL)=(U0/c0)(2)(R/deltanu)(2), with U0 the acoustic velocity amplitude at the
      velocity antinode, c0 the speed of sound, R the tube radius, and deltanu the
      acoustic boundary layer thickness]. Streaming velocity is measured by means of
      laser Doppler velocimetry in a cylindrical resonator filled with air at
      atmospheric pressure at high intensity sound levels. The compressible Navier
      Stokes equations are solved numerically with high resolution finite difference
      schemes. The resonator is excited by shaking it along the axis at imposed
      frequency. Results of measurements and of numerical calculation are compared with
      results given in the literature and with each other. As expected, the axial
      streaming velocity measured and calculated agrees reasonably well with the slow
      streaming theory for small ReNL but deviates significantly from such predictions
      for fast streaming (ReNL>1). Both experimental and numerical results show that
      when ReNL is increased, the center of the outer streaming cells are pushed toward
      the acoustic velocity nodes until counter-rotating additional vortices are
      generated near the acoustic velocity antinodes.

PMID- 23967914
TI  - Assessment of systematic measurement errors for acoustic travel-time tomography
      of the atmosphere.
AB  - Two algorithms are described for assessing systematic errors in acoustic travel
      time tomography of the atmosphere, the goal of which is to reconstruct the
      temperature and wind velocity fields given the transducers' locations and the
      measured travel times of sound propagating between each speaker-microphone pair.
      The first algorithm aims at assessing the errors simultaneously with the mean
      field reconstruction. The second algorithm uses the results of the first
      algorithm to identify the ray paths corrupted by the systematic errors and then
      estimates these errors more accurately. Numerical simulations show that the first
      algorithm can improve the reconstruction when relatively small systematic errors
      are present in all paths. The second algorithm significantly improves the
      reconstruction when systematic errors are present in a few, but not all, ray
      paths. The developed algorithms were applied to experimental data obtained at the
      Boulder Atmospheric Observatory. 

PMID- 23967915
TI  - Real-time reporting of baleen whale passive acoustic detections from ocean
      gliders.
AB  - In the past decade, much progress has been made in real-time passive acoustic
      monitoring of marine mammal occurrence and distribution from autonomous platforms
      (e.g., gliders, floats, buoys), but current systems focus primarily on a single
      call type produced by a single species, often from a single location. A hardware
      and software system was developed to detect, classify, and report 14 call types
      produced by 4 species of baleen whales in real time from ocean gliders. During a
      3-week deployment in the central Gulf of Maine in late November and early
      December 2012, two gliders reported over 25,000 acoustic detections attributed to
      fin, humpback, sei, and right whales. The overall false detection rate for
      individual calls was 14%, and for right, humpback, and fin whales, false
      predictions of occurrence during 15-min reporting periods were 5% or less.
      Transmitted pitch tracks--compact representations of sounds--allowed unambiguous
      identification of both humpback and fin whale song. Of the ten cases when whales
      were sighted during aerial or shipboard surveys and a glider was within 20 km of
      the sighting location, nine were accompanied by real-time acoustic detections of
      the same species by the glider within +/-12 h of the sighting time.

PMID- 23967916
TI  - Measuring the effect of ambient noise directionality and split-beam processing on
      the convergence of the cross-correlation function.
AB  - Measurements of ambient noise have been used to infer information about the ocean
      acoustic environment. In recent years the correlation of ambient noise has been
      shown to give estimates of the travel time of acoustic paths between the sensors
      recording the noise. A number of issues affect the results of the noise
      correlation. This paper presents the results of noise correlation of the two
      horizontally separated arrays of sensors in the 2010 ambient noise experiment.
      Using the experimental data, the effects on the convergence of the noise
      correlation are examined with respect to the size and shape of the arrays, the
      length of time used, and the directionality of the noise field. 

PMID- 23967917
TI  - Seabed roughness parameters from joint backscatter and reflection inversion at
      the Malta Plateau.
AB  - This paper presents estimates of seabed roughness and geoacoustic parameters and
      uncertainties on the Malta Plateau, Mediterranean Sea, by joint Bayesian
      inversion of mono-static backscatter and spherical wave reflection-coefficient
      data. The data are modeled using homogeneous fluid sediment layers overlying an
      elastic basement. The scattering model assumes a randomly rough water-sediment
      interface with a von Karman roughness power spectrum. Scattering and reflection
      data are inverted simultaneously using a population of interacting Markov chains
      to sample roughness and geoacoustic parameters as well as residual error
      parameters. Trans-dimensional sampling is applied to treat the number of sediment
      layers and the order (zeroth or first) of an autoregressive error model (to
      represent potential residual correlation) as unknowns. Results are considered in
      terms of marginal posterior probability profiles and distributions, which
      quantify the effective data information content to resolve scattering/geoacoustic
      structure. Results indicate well-defined scattering (roughness) parameters in
      good agreement with existing measurements, and a multi-layer sediment profile
      over a high-speed (elastic) basement, consistent with independent knowledge of
      sand layers over limestone. 

PMID- 23967918
TI  - Vertical coherence and forward scattering from the sea surface and the relation
      to the directional wave spectrum.
AB  - Results of an experiment to measure vertical spatial coherence from acoustic
      paths interacting once with the sea surface but at perpendicular azimuth angles
      are presented. The measurements were part of the Shallow Water 2006 program that
      took place off the coast of New Jersey in August 2006. An acoustic source,
      frequency range 6-20 kHz, was deployed at depth 40 m, and signals were recorded
      on a 1.4 m long vertical line array centered at depth 25 m and positioned at
      range 200 m. The vertical array consisted of four omni-directional hydrophones
      and vertical coherences were computed between pairs of these hydrophones.
      Measurements were made over four source-receiver bearing angles separated by 90
      degrees , during which sea surface conditions remained stable and characterized
      by a root-mean-square wave height of 0.17 m and a mixture of swell and wind
      waves. Vertical coherences show a statistically significant difference depending
      on source-receiver bearing when the acoustic frequency is less than about 12 kHz,
      with results tending to fade at higher frequencies. This paper presents field
      observations and comparisons of these observations with two modeling approaches,
      one based on bistatic forward scattering and the other on a rough surface
      parabolic wave equation utilizing synthetic sea surfaces.

PMID- 23967919
TI  - Interacting bubble clouds and their sonochemical production.
AB  - An acoustically driven air pocket trapped in a pit etched on a surface can emit a
      bubble cluster. When several pits are present, the resulting bubble clusters
      interact in a nontrivial way. Fernandez Rivas et al. [Angew. Chem. Int. Ed. 49,
      9699-9701 (2010)] observed three different behaviors at increasing driving power:
      clusters close to their "mother" pits, clusters attracting each other but still
      well separated, and merging clusters. The last is highly undesirable for
      technological purposes as it is associated with a reduction of the radical
      production and an enhancement of the erosion of the reactor walls. In this paper,
      the conditions for merging to occur are quantified in the case of two clusters,
      as a function of the following control parameters: driving pressure, distance
      between the two pits, cluster radius, and number of bubbles within each cluster.
      The underlying mechanism, governed by the secondary Bjerknes forces, is strongly
      influenced by the nonlinearity of the bubble oscillations and not directly by the
      number of nucleated bubbles. The Bjerknes forces are found to dampen the bubble
      oscillations, thus reducing the radical production. Therefore, the increased
      number of bubbles at high power could be the key to understanding the
      experimental observation that, above a certain power threshold, any further
      increase of the driving does not improve the sonochemical efficiency. 

PMID- 23967920
TI  - Ultrasonic wave propagation in thermoviscous moving fluid confined by heating
      pipeline and flow measurement performance.
AB  - Ultrasonic wave propagation in thermoviscous fluid with pipeline shear mean flow
      in the presence of a temperature gradient is investigated. On the assumption of
      irrotational and axisymmetric wave propagation, a mathematical formulation of the
      convected wave equation is proposed without simplification in the manner of
      Zwikker and Kosten. A method based on the Fourier-Bessel theory, which is
      complete and orthogonal in Lebesgue space, is introduced to convert the wave
      equations into homogeneous algebraic equations. Then numerical calculation of the
      axial wavenumber is presented. In the end, wave attenuation in laminar and
      turbulent flow is numerically studied. Meanwhile measurement performance of an
      ultrasonic flow meter is parametrically analyzed. 

PMID- 23967922
TI  - Antisymmetric feature-guided ultrasonic waves in thin plates with small radius
      transverse bends from low-frequency symmetric axial excitation.
AB  - The influence of bends constituting annular polygonal structures on ultrasonic
      guided waves propagating along their axis is investigated. Considering a single
      bend as a bent plate connects this problem to the better-understood physics of
      guided waves in straight plates. Using a three-dimensional finite element
      simulation validated with experiments, bends in plates are shown to act as
      features that can concentrate and guide ultrasonic energy along their length. Two
      interesting feature-guided modes are identified when the bent plate is subjected
      to "in-plane" or axial excitation applied uniformly along a through-thickness
      line bisecting the bent edge. Of these, the faster traveling mode has properties
      similar to, but travels at group velocities lower than, the S0 (fundamental
      symmetric) Lamb mode in flat plates. This paper however focuses on the slower
      bend-guided mode that is similar to the A0 (fundamental anti-symmetric) Lamb mode
      in flat plates. This mode is shown to be more strongly generated in smaller angle
      bends where it has a low attenuation. The results are discussed in light of
      simple modal studies performed using the Semi-Analytical Finite Element method. 

PMID- 23967921
TI  - Mechanisms of microbubble-vessel interactions and induced stresses: a numerical
      study.
AB  - Oscillating microbubbles within microvessels could induce stresses that lead to
      bioeffects or vascular damage. Previous work has attributed vascular damage to
      the vessel expansion or bubble jet. However, ultra-high speed images of recent
      studies suggest that it could happen due to the vascular invagination. Numerical
      simulations of confined bubbles could provide insight into understanding the
      mechanism behind bubble-vessel interactions. In this study, a finite element
      model of a coupled bubble/fluid/vessel system was developed and validated with
      experimental data. Also, for a more realistic study viscoelastic properties of
      microvessels were assessed and incorporated into this comprehensive numerical
      model. The wall shear stress (WSS) and circumferential stress (CS), metrics of
      vascular damage, were calculated from these simulations. Resultant amplitudes of
      oscillation were within 15% of those measured in experiments (four cases). Among
      the experimental cases, it was numerically found that maximum WSS values were
      between 1.1-18.3 kPa during bubble expansion and 1.5-74 kPa during bubble
      collapse. CS was between 0.43-2.2 MPa during expansion and 0.44-6 MPa while
      invaginated. This finding confirmed that vascular damage could occur during
      vascular invaginations. Predicted thresholds in which these stresses are higher
      during vessel invagination were calculated from simulations.

PMID- 23967923
TI  - Realization of an omnidirectional source of sound using parametric loudspeakers.
AB  - Parametric loudspeakers are often used in beam forming applications where a high
      directivity is required. Withal, in this paper it is proposed to use such devices
      to build an omnidirectional source of sound. An initial prototype, the
      omnidirectional parametric loudspeaker (OPL), consisting of a sphere with
      hundreds of ultrasonic transducers placed on it has been constructed. The OPL
      emits audible sound thanks to the parametric acoustic array phenomenon, and the
      close proximity and the large number of transducers results in the generation of
      a highly omnidirectional sound field. Comparisons with conventional dodecahedron
      loudspeakers have been made in terms of directivity, frequency response, and in
      applications such as the generation of diffuse acoustic fields in reverberant
      chambers. The OPL prototype has performed better than the conventional
      loudspeaker especially for frequencies higher than 500 Hz, its main drawback
      being the difficulty to generate intense pressure levels at low frequencies.

PMID- 23967924
TI  - Fluid-structure effects of cloaking a submerged spherical shell.
AB  - Backscattering from a cloaked submerged spherical shell is analyzed in the low,
      mid, and high frequency regimes. Complex poles of the scattered pressure
      amplitudes using Cauchy residue theory are evaluated in an effort to explain
      dominant features of the scattered pressure and how they are affected by the
      introduction of a cloak. The methodology used is similar to that performed by
      Sammelmann and Hackman [J. Acoust. Soc. Am. 85, 114-124 (1989); J. Acoust. Soc.
      Am. 89, 2096-2103 (1991); J. Acoust. Soc. Am. 90, 2705-2717 (1991)] in a series
      of papers written on scattering from an uncloaked spherical shell. In general, it
      is found that cloaking has the effect of diminishing the amplitude and shifting
      tonal backscatter responses. Extreme changes of normal and tangential fluid phase
      velocities at the fluid-solid interface when cloaking is employed leads to
      elimination of the "mid-frequency enhancement" near the coincidence frequency for
      even modestly effective cloaks, while reduction of the "high-frequency
      enhancement" resulting from the "thickness quasi-resonance" near the cut-off
      frequency of the symmetric (S2(B)) mode requires more effective cloaking, but can
      be practically eliminated by employing a cloak that creates tangential acoustic
      velocities in excess of the S2(B) mode phase speed near cutoff.

PMID- 23967925
TI  - Modeling of wave propagation in drill strings using vibration transfer matrix
      methods.
AB  - In order to understand critical vibration of a drill bit such as stick-slip and
      bit-bounce and their wave propagation characteristics through a drill string
      system, it is critical to model the torsional, longitudinal, and flexural waves
      generated by the drill bit vibration. Here, a modeling method based on a
      vibration transfer matrix between two sets of structural wave variables at the
      ends of a constant cross-sectional, hollow, circular pipe is proposed. For a
      drill string system with multiple pipe sections, the total vibration transfer
      matrix is calculated by multiplying all individual matrices, each is obtained for
      an individual pipe section. Since drill string systems are typically extremely
      long, conventional numerical analysis methods such as a finite element method
      (FEM) require a large number of meshes, which makes it computationally
      inefficient to analyze these drill string systems numerically. The proposed
      "analytical" vibration transfer matrix method requires significantly low
      computational resources. For the validation of the proposed method, experimental
      and numerical data are obtained from laboratory experiments and FEM analyses
      conducted by using a commercial FEM package, ANSYS. It is shown that the modeling
      results obtained by using the proposed method are well matched with the
      experimental and numerical results. 

PMID- 23967926
TI  - Narrow band noise response of a Belleville spring resonator.
AB  - This study of nonlinear dynamics includes (i) an identification of quasi-steady
      states of response using equivalent linearization, (ii) the temporal simulation
      of the system using Heun's time step procedure on time domain analytic signals,
      and (iii) a laboratory experiment. An attempt has been made to select material
      and measurement parameters so that nearly the same systems are used and analyzed
      for all three parts of the study. This study illustrates important features of
      nonlinear response to narrow band excitation: (a) states of response that the
      system can acquire with transitions of the system between those states, (b) the
      interaction between the noise source and the vibrating load in which the source
      transmits energy to or draws energy from the load as transitions occur; (c) the
      lag or lead of the system response relative to the source as transitions occur
      that causes the average frequencies of source and response to differ; and (d) the
      determination of the state of response (mass or stiffness controlled) by
      observation of the instantaneous phase of the influence function. These analyses
      take advantage of the use of time domain analytic signals that have a
      complementary role to functions that are analytic in the frequency domain. 

PMID- 23967927
TI  - Scattering of a fluid-structure coupled wave at a flanged junction between two
      flexible waveguides.
AB  - The scattering of a fluid-structure coupled wave at a flanged junction between
      two flexible waveguides is investigated. The flange is assumed to be rigid on one
      side and soft on the other; this enables a solution to be formulated using mode
      matching. It is shown that both the choice of the edge conditions imposed on the
      plates at the junction and the choice of incident forcing significantly affect
      the transmission of energy along the duct. In particular, the edge conditions
      crucially affect the transmission of structure-borne vibration but have little
      effect on fluid-borne noise. Given the singular nature of the velocity field at
      the flange tip, particular attention is paid to the validity of the mode-matching
      method. It is demonstrated that the velocity field can be accurately
      reconstructed by incorporating the Lanczos filter into the truncated modal
      expansions. The mode-matching method is thus confirmed as an viable tool for this
      class of problem. 

PMID- 23967928
TI  - Local resonance bandgaps in periodic media: theory and experiment.
AB  - Periodic composites such as acoustic metamaterials use local resonance phenomenon
      in designing low frequency sub-Bragg bandgaps. These bandgaps emerge from a
      resonant scattering interaction between a propagating wave and periodically
      arranged resonators. This paper develops a receptance coupling technique to
      combine the dynamics of the resonator with the unit cell dynamics of the
      background medium to analyze flexural wave transmission in a periodic structure,
      involving a single degree of freedom coupling between the medium and the
      resonator. Receptance techniques allow for a straightforward extension to higher
      dimensional systems with multiple degrees of freedom coupling and for easier
      experimental measurements. Closed-form expressions for the location and width of
      sub-Bragg bandgaps are obtained. Rigid body modes of the unit cell of the
      background medium are shown to set the bounding frequencies for local resonance
      bandgaps. Results from the receptance analysis compare well with Bloch wave
      analysis and experiments performed on a finite structural beam with periodic
      masses and resonators. Stronger coupling and inertia of the resonator increase
      the local resonance bandgap width. Two-fold periodicity widens the Bragg bandgap,
      narrowed by local resonators, thus expanding the design space and highlighting
      the advantages of hierarchical periodicity. 

PMID- 23967929
TI  - A mechanism study of sound wave-trapping barriers.
AB  - The performance of a sound barrier is usually degraded if a large reflecting
      surface is placed on the source side. A wave-trapping barrier (WTB), with its
      inner surface covered by wedge-shaped structures, has been proposed to confine
      waves within the area between the barrier and the reflecting surface, and thus
      improve the performance. In this paper, the deterioration in performance of a
      conventional sound barrier due to the reflecting surface is first explained in
      terms of the resonance effect of the trapped modes. At each resonance frequency,
      a strong and mode-controlled sound field is generated by the noise source both
      within and in the vicinity outside the region bounded by the sound barrier and
      the reflecting surface. It is found that the peak sound pressures in the
      barrier's shadow zone, which correspond to the minimum values in the barrier's
      insertion loss, are largely determined by the resonance frequencies and by the
      shapes and losses of the trapped modes. These peak pressures usually result in
      high sound intensity component impinging normal to the barrier surface near the
      top. The WTB can alter the sound wave diffraction at the top of the barrier if
      the wavelengths of the sound wave are comparable or smaller than the dimensions
      of the wedge. In this case, the modified barrier profile is capable of re
      organizing the pressure distribution within the bounded domain and altering the
      acoustic properties near the top of the sound barrier. 

PMID- 23967930
TI  - Irrelevant speech effect under stationary and adaptive masking conditions.
AB  - The irrelevant speech effect was investigated in this study where the serial
      recall task was performed under six different conditions: Silence, speech-only,
      noise-only, speech masked by a stationary noise at two different signal-to-noise
      ratios (SNRs), and speech masked by an adaptive noise. Measured in five test
      blocks distributed throughout the four test days, the error rate of the serial
      recall task under the silence condition sharply decreased in the first few test
      blocks, halved after completing about seven blocks. When the adaptive masking
      scheme was used, the error rate of the serial-recall test was reduced compared to
      the speech-only condition (by 9%) and to the lower-SNR stationary noise (by
      4.4%). However, the serial-recall performance was not significantly different
      between the stationary and the adaptive maskers when the average sound level was
      carefully matched. Speech Transmission Index (STI) and the correlation
      coefficient of power spectra were used as the estimators of the temporal and
      spectral distinctiveness between sound tokens, respectively. The comparison to
      the test results implied that the frequency-domain estimator may be a better
      predictor of the relative ISE especially for a non-stationary masker, although it
      was also suggested that such estimators may have to be combined possibly with an
      appropriate weighting. 

PMID- 23967931
TI  - Unsteady numerical simulation of a round jet with impinging microjets for noise
      suppression.
AB  - The objective of this study was to determine the feasibility of a lattice
      Boltzmann method (LBM)-Large Eddy Simulation methodology for the prediction of
      sound radiation from a round jet-microjet combination. The distinct advantage of
      LBM over traditional computational fluid dynamics methods is its ease of handling
      problems with complex geometries. Numerical simulations of an isothermal Mach
      0.5, Re(D) = 1 * 10(5) circular jet (D(j) = 0.0508 m) with and without the
      presence of 18 microjets (D(mj) = 1 mm) were performed. The presence of microjets
      resulted in a decrease in the axial turbulence intensity and turbulent kinetic
      energy. The associated decrease in radiated sound pressure level was around 1 dB.
      The far-field sound was computed using the porous Ffowcs Williams-Hawkings
      surface integral acoustic method. The trend obtained is in qualitative agreement
      with experimental observations. The results of this study support the accuracy of
      LBM based numerical simulations for predictions of the effects of noise
      suppression devices on the radiated sound power.

PMID- 23967932
TI  - Modeling, analysis, and validation of an active T-shaped noise barrier.
AB  - With ever-increasing land traffic, abatement of traffic noise using noise
      barriers remains significant, yet it is a challenging task due to spatial
      competition with other infrastructure. In this study, a deep insight into the
      diffraction characteristics of acoustic fields near noise barriers of various
      geometries and surface conditions was achieved using numerical simulations. A T
      shaped passive noise barrier with acoustically soft upper surfaces was
      demonstrated to outperform other candidates in a middle- or high-frequency range.
      Based on attributes of the acoustic field diffracted by T-shaped barriers, an
      active control strategy was developed to revamp the T-shaped barrier, in which a
      filtered minimax algorithm was established to drive the secondary sound sources.
      This algorithm resulted in more uniformly distributed residual sound fields than
      a filtered-X least mean square algorithm. Performance of the actively controlled
      barrier was evaluated at different positions and spacings of secondary sound
      sources and error sensors, leading to a series of optimal criteria for the design
      of active noise barriers. A prototype was fabricated and validated
      experimentally, manifesting particular effectiveness in insulating low-frequency
      noise, supplementing well the capacity of a passive T-shaped barrier which is
      effective in the middle- or high-frequency range. 

PMID- 23967933
TI  - On-road and wind-tunnel measurement of motorcycle helmet noise.
AB  - The noise source mechanisms involved in motorcycling include various aerodynamic
      sources and engine noise. The problem of noise source identification requires
      extensive data acquisition of a type and level that have not previously been
      applied. Data acquisition on track and on road are problematic due to rider
      safety constraints and the portability of appropriate instrumentation. One way to
      address this problem is the use of data from wind tunnel tests. The validity of
      these measurements for noise source identification must first be demonstrated. In
      order to achieve this extensive wind tunnel tests have been conducted and
      compared with the results from on-track measurements. Sound pressure levels as a
      function of speed were compared between on track and wind tunnel tests and were
      found to be comparable. Spectral conditioning techniques were applied to separate
      engine and wind tunnel noise from aerodynamic noise and showed that the
      aerodynamic components were equivalent in both cases. The spectral conditioning
      of on-track data showed that the contribution of engine noise to the overall
      noise is a function of speed and is more significant than had previously been
      thought. These procedures form a basis for accurate experimental measurements of
      motorcycle noise. 

PMID- 23967934
TI  - Enhanced awakening probability of repetitive impulse sounds.
AB  - In the present study relations between the level of impulse sounds and the
      observed proportion of behaviorally confirmed awakening reactions were
      determined. The sounds (shooting sounds, bangs produced by door slamming or by
      container transshipment, aircraft landings) were presented by means of
      loudspeakers in the bedrooms of 50 volunteers. The fragments for the impulse
      sounds consisted of single or multiple events. The sounds were presented during a
      6-h period that started 75 min after the subjects wanted to sleep. In order to
      take account of habituation, each subject participated during 18 nights. At equal
      indoor A-weighted sound exposure levels, the proportion of awakening for the
      single impulse sounds was equal to that for the aircraft sounds. The proportion
      of awakening induced by the multiple impulse sounds, however, was significantly
      higher. For obtaining the same rate of awakening, the sound level of each of the
      successive impulses in a fragment had to be about 15-25 dB lower than the level
      of one single impulse. This level difference was largely independent of the
      degree of habituation. Various explanations for the enhanced awakening
      probability are discussed.

PMID- 23967935
TI  - Designing sound and visual components for enhancement of urban soundscapes.
AB  - The aim of this study is to investigate the effect of audio-visual components on
      environmental quality to improve soundscape. Natural sounds with road traffic
      noise and visual components in urban streets were evaluated through laboratory
      experiments. Waterfall and stream water sounds, as well as bird sounds, were
      selected to enhance the soundscape. Sixteen photomontages of a streetscape were
      constructed in combination with two types of water features and three types of
      vegetation which were chosen as positive visual components. The experiments
      consisted of audio-only, visual-only, and audio-visual conditions. The
      preferences and environmental qualities of the stimuli were evaluated by a
      numerical scale and 12 pairs of adjectives, respectively. The results showed that
      bird sounds were the most preferred among the natural sounds, while the sound of
      falling water was found to degrade the soundscape quality when the road traffic
      noise level was high. The visual effects of vegetation on aesthetic preference
      were significant, but those of water features relatively small. It was revealed
      that the perceptual dimensions of the environment were different from the noise
      levels. Particularly, the acoustic comfort factor related to soundscape quality
      considerably influenced preference for the overall environment at a higher level
      of road traffic noise. 

PMID- 23967936
TI  - Optimizing stepwise rotation of dodecahedron sound source to improve the accuracy
      of room acoustic measures.
AB  - Dodecahedron sound sources are widely used for acoustical measurement purposes as
      they produce a good approximation of omnidirectional radiation. Evidence shows
      that such an assumption is acceptable only in the low-frequency range (namely
      below 1 kHz), while at higher frequencies sound radiation is far from being
      uniform. In order to improve the accuracy of acoustical measurements obtained
      from dodecahedron sources, international standard ISO 3382 suggests an averaging
      of results after a source rotation. This paper investigates the effects of such
      rotations, both in terms of variations in acoustical parameters and spatial
      distribution of sound reflections. Taking advantage of a spherical microphone
      array, the different reflection patterns were mapped as a function of source
      rotation, showing that some reflections may be considerably attenuated for
      different aiming directions. This paper investigates the concept of averaging
      results while changing rotation angles and the minimum number of rotations
      required to improve the accuracy of the average value. Results show that averages
      of three measurements carried out at 30 degrees  angular steps are closer to
      actual values and show much less fluctuation. In addition, an averaging of the
      directional intensity components of the selected responses stabilizes the spatial
      distribution of the reflections. 

PMID- 23967937
TI  - Neural network predictions of acoustical parameters in multi-purpose performance
      halls.
AB  - A detailed binaural sound measurement was carried out in two multi-purpose
      performance halls of different seating capacities and designs in Hong Kong in the
      present study. The effectiveness of using neural network in the predictions of
      the acoustical properties using a limited number of measurement points was
      examined. The root-mean-square deviation from measurements, statistical parameter
      distribution matching, and the results of a t-test for vanishing mean difference
      between simulations and measurements were adopted as the evaluation criteria for
      the neural network performance. The audience locations relative to the sound
      source were used as the inputs to the neural network. Results show that the
      neural network training scheme using nine uniformly located measurement points in
      each specific hall area is the best choice regardless of the hall setting and
      design. It is also found that the neural network prediction of hall spaciousness
      does not require a large amount of training data, but the accuracy of the
      reverberance related parameter predictions increases with increasing volume of
      training data. 

PMID- 23967938
TI  - Optimal irregular microphone distributions with enhanced beamforming performance
      in immersive environments.
AB  - Complex relationships between array gain patterns and microphone distributions
      limit the application of optimization algorithms on irregular arrays. This paper
      proposes a Genetic Algorithm (GA) for microphone array optimization in immersive
      (near-field) environments. Geometric descriptors for irregular arrays are
      proposed for use as objective functions to reduce optimization time by
      circumventing the need for direct array gain computations. In addition,
      probabilistic descriptions of acoustic scenes are introduced for incorporating
      prior knowledge of the source distribution. To verify the effectiveness of the
      proposed optimization, signal-to-noise ratios are compared for GA-optimized
      arrays, regular arrays, and arrays optimized through direct exhaustive
      simulations. Results show enhancements for GA-optimized arrays over arbitrary
      randomly generated arrays and regular arrays, especially at low microphone
      densities where placement becomes critical. Design parameters for the GA are
      identified for improving optimization robustness for different applications. The
      rapid convergence and acceptable processing times observed during the experiments
      establish the feasibility of this approach for optimizing array geometries in
      immersive environments where rapid deployment is required with limited knowledge
      of the acoustic scene, such as in mobile platforms and audio surveillance
      applications. 

PMID- 23967939
TI  - Deconvolution for the localization of sound sources using a circular microphone
      array.
AB  - During the last decade, the aeroacoustic community has examined various methods
      based on deconvolution to improve the visualization of acoustic fields scanned
      with planar sparse arrays of microphones. These methods assume that the
      beamforming map in an observation plane can be approximated by a convolution of
      the distribution of the actual sources and the beamformer's point-spread
      function, defined as the beamformer's response to a point source. By deconvolving
      the resulting map, the resolution is improved, and the side-lobes effect is
      reduced or even eliminated compared to conventional beamforming. Even though
      these methods were originally designed for planar sparse arrays, in the present
      study, they are adapted to uniform circular arrays for mapping the sound over 360
      degrees . This geometry has the advantage that the beamforming output is
      practically independent of the focusing direction, meaning that the beamformer's
      point-spread function is shift-invariant. This makes it possible to apply
      computationally efficient deconvolution algorithms that consist of spectral
      procedures in the entire region of interest, such as the deconvolution approach
      for the mapping of the acoustic sources 2, the Fourier-based non-negative least
      squares, and the Richardson-Lucy. This investigation examines the matter with
      computer simulations and measurements. 

PMID- 23967940
TI  - Acoustic mapping of ocean currents using networked distributed sensors.
AB  - Distributed underwater sensors are expected to provide oceanographic monitoring
      over large areas. As fabrication technology advances, low cost sensors will be
      available for many uses. The sensors communicate to each other and are networked
      using acoustic communications. This paper first studies the performance of such
      systems for current measurements using tomographic inversion approaches to
      compare with that of a conventional system which distributes the sensors on the
      periphery of the area of interest. It then proposes two simple signal processing
      methods for ocean current mapping (using distributed networked sensors) aimed at
      real-time in-buoy processing. Tomographic inversion generally requires solving a
      challenging high dimensional inverse problem, involving substantial computations.
      Given distributed sensors, currents can be constructed locally based on data from
      neighboring sensors. It is shown using simulated data that similar results are
      obtained using distributed processing as using conventional tomographic
      approaches. The advantage for distributed systems is that by increasing the
      number of nodes, one gains a much more improved performance. Furthermore,
      distributed systems use much less energy than a conventional tomographic system
      for the same area coverage. Experimental data from an acoustic communication and
      networking experiment are used to demonstrate the feasibility of acoustic current
      mapping. 

PMID- 23967941
TI  - Wave field synthesis of a virtual source located in proximity to a loudspeaker
      array.
AB  - For the derivation of 2.5-dimensional operator in wave field synthesis, a virtual
      source is assumed to be positioned far from a loudspeaker array. However, such
      far-field approximation inevitably results in a reproduction error when the
      virtual source is placed adjacent to an array. In this paper, a method is
      proposed to generate a virtual source close to and behind a continuous line array
      of loudspeakers. A driving function is derived by reducing a surface integral
      (Rayleigh integral) to a line integral based on the near-field assumption. The
      solution is then combined with the far-field formula of wave field synthesis by
      introducing a weighting function that can adjust the near- and far-field
      contribution of each driving function. This enables production of a virtual
      source anywhere in relation to the array. Simulations show the proposed method
      can reduce the reproduction error to below -18 dB, regardless of the virtual
      source position.

PMID- 23967942
TI  - Theoretical analysis of signal-to-noise ratios for transient evoked otoacoustic
      emission recordings.
AB  - Recordings of transient-evoked otoacoustic emissions (TEOAEs) suffer from two
      main sources of contamination: Random noise and the stimulus artifact. The
      stimulus artifact can be substantially reduced by using a derived non-linear
      recording paradigm. Three such paradigms are analyzed, called here the level
      derived non-linear (LDNL), the double-evoked (DE), and the rate derived non
      linear (RDNL) paradigms. While these methods successfully reduce the stimulus
      artifact, they lead to an increase in contamination by random noise. In this
      study, the signal-to-noise ratio (SNR) achievable by these three paradigms is
      compared using a common theoretical framework. This analysis also allows the
      optimization of the parameters of the RDNL paradigm to achieve the maximum SNR.
      Calculations based on the analysis with typical parameters used in practice
      suggest that when ranked in terms of their SNR for a given averaging time, RDNL
      performs best followed by the LDNL and DE paradigms. 

PMID- 23967943
TI  - Short-latency transient-evoked otoacoustic emissions as predictors of hearing
      status and thresholds.
AB  - Estimating audiometric thresholds using objective measures can be clinically
      useful when reliable behavioral information cannot be obtained. Transient-evoked
      otoacoustic emissions (TEOAEs) are effective for determining hearing status
      (normal hearing vs hearing loss), but previous studies have found them less
      useful for predicting audiometric thresholds. Recent work has demonstrated the
      presence of short-latency TEOAE components in normal-hearing ears, which have
      typically been eliminated from the analyses used in previous studies. The current
      study investigated the ability of short-latency components to predict hearing
      status and thresholds from 1-4 kHz. TEOAEs were measured in 77 adult ears with
      thresholds ranging from normal hearing to moderate sensorineural hearing loss.
      Emissions were bandpass filtered at center frequencies from 1 to 4 kHz. TEOAE
      waveforms were analyzed within two time windows that contained either short- or
      long-latency components. Waveforms were quantified by root-mean-square amplitude.
      Long-latency components were better overall predictors of hearing status and
      thresholds, relative to short-latency components. There were no significant
      improvements in predictions when short-latency components were included with long
      latency components in multivariate analyses. The results showed that short
      latency TEOAE components, as analyzed in the current study, were less predictive
      of both hearing status and thresholds from 1-4 kHz than long-latency components.

PMID- 23967945
TI  - Effect of long-term training on sound localization performance with spectrally
      warped and band-limited head-related transfer functions.
AB  - Sound localization in the sagittal planes, including the ability to distinguish
      front from back, relies on spectral features caused by the filtering effects of
      the head, pinna, and torso. It is assumed that important spatial cues are encoded
      in the frequency range between 4 and 16 kHz. In this study, in a double-blind
      design and using audio-visual training covering the full 3-D space, normal
      hearing listeners were trained 2 h per day over three weeks to localize sounds
      which were either band limited up to 8.5 kHz or spectrally warped from the range
      between 2.8 and 16 kHz to the range between 2.8 and 8.5 kHz. The training effect
      for the warped condition exceeded that for procedural task learning, suggesting a
      stable auditory recalibration due to the training. After the training,
      performance with band-limited sounds was better than that with warped ones. The
      results show that training can improve sound localization in cases where spectral
      cues have been reduced by band-limiting or remapped by warping. This suggests
      that hearing-impaired listeners, who have limited access to high frequencies,
      might also improve their localization ability when provided with spectrally
      warped or band-limited sounds and adequately trained on sound localization.

PMID- 23967944
TI  - Acoustical correlates of performance on a dynamic range compression
      discrimination task.
AB  - Dynamic range compression is widely used to reduce the difference between the
      most and least intense portions of a signal. Such compression distorts the shape
      of the amplitude envelope of a signal, but it is unclear to what extent such
      distortions are actually perceivable by listeners. Here, the ability to
      distinguish between compressed and uncompressed versions of a noise vocoded
      sentence was initially measured in listeners with normal hearing while varying
      the threshold, ratio, attack, and release parameters. This narrow condition was
      selected in order to characterize perception under the most favorable listening
      conditions. The average behavioral sensitivity to compression was highly
      correlated to several acoustical indices of modulation depth. In particular,
      performance was highly correlated to the Euclidean distance between the
      modulation spectra of the uncompressed and compressed signals. Suggesting that
      this relationship is not restricted to the initial test conditions, the
      correlation remained largely unchanged both (1) when listeners with normal
      hearing were tested using a time-compressed version of the original signal, and
      (2) when listeners with impaired hearing were tested using the original signal.
      If this relationship generalizes to more ecologically valid conditions, it will
      provide a straightforward method for predicting the detectability of compression
      induced distortions. 

PMID- 23967946
TI  - The information-divergence hypothesis of informational masking.
AB  - In recent years there has been growing interest in masking that cannot be
      attributed to interactions in the cochlea-so--called informational masking (IM).
      Similarity in the acoustic properties of target and masker and uncertainty
      regarding the masker are the two major factors identified with IM. These factors
      involve quite different manipulations of signals and are believed to entail
      fundamentally different processes resulting in IM. Here, however, evidence is
      presented that these factors affect IM through their mutual influence on a single
      factor-the information divergence of target and masker given by Simpson-Fitter's
      da [Lutfi et al. (2012). J. Acoust. Soc. Am. 132, EL109-113]. Four experiments
      are described involving multitone pattern discrimination, multi-talker word
      recognition, sound-source identification, and sound localization. In each case
      standard manipulations of masker uncertainty and target-masker similarity
      (including the covariation of target-masker frequencies) are found to have the
      same effect on performance provided they produce the same change in da. The
      function relating d(') performance to da, moreover, appears to be linear with
      constant slope across listeners. The overriding dependence of IM on da is taken
      to reflect a general principle of perception that exploits differences in the
      statistical structure of signals to separate figure from ground.

PMID- 23967947
TI  - Imprecise vowel articulation as a potential early marker of Parkinson's disease:
      effect of speaking task.
AB  - The purpose of this study was to analyze vowel articulation across various
      speaking tasks in a group of 20 early Parkinson's disease (PD) individuals prior
      to pharmacotherapy. Vowels were extracted from sustained phonation, sentence
      repetition, reading passage, and monologue. Acoustic analysis was based upon
      measures of the first (F1) and second (F2) formant of the vowels /a/, /i/, and
      /u/, vowel space area (VSA), F2i/F2u and vowel articulation index (VAI).
      Parkinsonian speakers manifested abnormalities in vowel articulation across F2u,
      VSA, F2i/F2u, and VAI in all speaking tasks except sustained phonation, compared
      to 15 age-matched healthy control participants. Findings suggest that sustained
      phonation is an inappropriate task to investigate vowel articulation in early PD.
      In contrast, monologue was the most sensitive in differentiating between controls
      and PD patients, with classification accuracy up to 80%. Measurements of vowel
      articulation were able to capture even minor abnormalities in speech of PD
      patients with no perceptible dysarthria. In conclusion, impaired vowel
      articulation may be considered as a possible early marker of PD. A certain type
      of speaking task can exert significant influence on vowel articulation.
      Specifically, complex tasks such as monologue are more likely to elicit
      articulatory deficits in parkinsonian speech, compared to other speaking tasks. 

PMID- 23967948
TI  - Accounting for the listener: comparing the production of contrastive intonation
      in typically-developing speakers and speakers with autism.
AB  - The present research investigates what drives the prosodic marking of contrastive
      information. For example, a typically developing speaker of a Germanic language
      like Dutch generally refers to a pink car as a "PINK car" (accented words in
      capitals) when a previously mentioned car was red. The main question addressed in
      this paper is whether contrastive intonation is produced with respect to the
      speaker's or (also) the listener's perspective on the preceding discourse.
      Furthermore, this research investigates the production of contrastive intonation
      by typically developing speakers and speakers with autism. The latter group is
      investigated because people with autism are argued to have difficulties
      accounting for another person's mental state and exhibit difficulties in the
      production and perception of accentuation and pitch range. To this end,
      utterances with contrastive intonation are elicited from both groups and analyzed
      in terms of function and form of prosody using production and perception
      measures. Contrary to expectations, typically developing speakers and speakers
      with autism produce functionally similar contrastive intonation as both groups
      account for both their own and their listener's perspective. However, typically
      developing speakers use a larger pitch range and are perceived as speaking more
      dynamically than speakers with autism, suggesting differences in their use of
      prosodic form. 

PMID- 23967949
TI  - Contribution of envelope periodicity to release from speech-on-speech masking.
AB  - Masking release (MR) is the improvement in speech intelligibility for a
      fluctuating interferer compared to stationary noise. Reduction in MR due to
      vocoder processing is usually linked to distortions in the temporal fine
      structure of the stimuli and a corresponding reduction in the fundamental
      frequency (F0) cues. However, it is unclear if envelope periodicity related to
      F0, produced by the interaction between unresolved harmonics, contributes to MR.
      In the present study, MR was determined from speech reception thresholds measured
      in the presence of stationary speech-shaped noise and a competing talker. Two
      types of processing were applied to the stimuli: (1) An amplitude- and frequency
      modulated vocoder attenuated the envelope periodicity and (2) high-pass (HP)
      filtering (cutoff = 500 Hz) reduced the influence of F0-related information from
      low-order resolved harmonics. When applied individually, MR was unaffected by HP
      filtering, but slightly reduced when envelope periodicity was attenuated. When
      both were applied, MR was strongly reduced. Thus, the results indicate that F0
      related information is crucial for MR, but that it is less important whether the
      F0-related information is conveyed by low-order resolved harmonics or by envelope
      periodicity as a result of unresolved harmonics. Further, envelope periodicity
      contributes substantially to MR.

PMID- 23967950
TI  - Role and relative contribution of temporal envelope and fine structure cues in
      sentence recognition by normal-hearing listeners.
AB  - The present study investigated the role and relative contribution of envelope and
      temporal fine structure (TFS) to sentence recognition in noise. Target and masker
      stimuli were added at five different signal-to-noise ratios (SNRs) and filtered
      into 30 contiguous frequency bands. The envelope and TFS were extracted from each
      band by Hilbert decomposition. The final stimuli consisted of the envelope of the
      target/masker sound mixture at x dB SNR and the TFS of the same sound mixture at
      y dB SNR. A first experiment showed a very limited contribution of TFS cues,
      indicating that sentence recognition in noise relies almost exclusively on
      temporal envelope cues. A second experiment showed that replacing the carrier of
      a sound mixture with noise (vocoder processing) cannot be considered equivalent
      to disrupting the TFS of the target signal by adding a background noise.
      Accordingly, a re-evaluation of the vocoder approach as a model to further
      understand the role of TFS cues in noisy situations may be necessary. Overall,
      these data are consistent with the view that speech information is primarily
      extracted from the envelope while TFS cues are primarily used to detect glimpses
      of the target. 

PMID- 23967951
TI  - Auditory enhancement and second language experience in Spanish and English
      weighting of secondary voicing cues.
AB  - The role of secondary cues in voicing categorization was investigated in three
      listener groups: Monolingual English (n = 20) and Spanish speakers (n = 20), and
      Spanish speakers with significant English experience (n = 16). Results showed
      that, in all three groups, participants used onset f0 in making voicing decisions
      only in the positive voice onset time (VOT) range (short lag and long lag
      tokens), while there was no effect of onset f0 on voicing categorization within
      the negative VOT range (voicing lead tokens) for any of the participant groups.
      These results support an auditory enhancement view of perceptual cue weighting:
      Onset f0 serves as a secondary cue to voicing only in the positive VOT range
      where it is not overshadowed by the presence of pre-voicing. Moreover, results
      showed that Spanish learners of English gave a significantly greater weight to
      onset f0 in their voicing decisions than did listeners in either of the other two
      groups. This result supports the view that learners may overweight secondary cues
      to distinguish between non-native categories that are assimilated to the same
      native category on the basis of a primary cue.

PMID- 23967952
TI  - The effects of working memory capacity and semantic cues on the intelligibility
      of speech in noise.
AB  - This study examined how semantically related information facilitates the
      intelligibility of spoken sentences in the presence of masking sound, and how
      this facilitation is influenced by masker type and by individual differences in
      cognitive functioning. Dutch sentences were masked by stationary noise,
      fluctuating noise, or an interfering talker. Each sentence was preceded by a text
      cue; cues were either three words that were semantically related to the sentence
      or three unpronounceable nonwords. Speech reception thresholds were adaptively
      measured. Additional measures included working memory capacity (reading span and
      size comparison span), linguistic closure ability (text reception threshold), and
      delayed sentence recognition. Word cues facilitated speech perception in noise
      similarly for all masker types. Cue benefit was related to reading span
      performance when the masker was interfering speech, but not when other maskers
      were used, and it did not correlate with text reception threshold or size
      comparison span. Better reading span performance was furthermore associated with
      enhanced delayed recognition of sentences preceded by word relative to nonword
      cues, across masker types. The results suggest that working memory capacity is
      associated with release from informational masking by semantically related
      information, and additionally with the encoding, storage, or retrieval of speech
      content in memory. 

PMID- 23967953
TI  - Using automatic alignment to analyze endangered language data: testing the
      viability of untrained alignment.
AB  - While efforts to document endangered languages have steadily increased, the
      phonetic analysis of endangered language data remains a challenge. The
      transcription of large documentation corpora is, by itself, a tremendous feat.
      Yet, the process of segmentation remains a bottleneck for research with data of
      this kind. This paper examines whether a speech processing tool, forced
      alignment, can facilitate the segmentation task for small data sets, even when
      the target language differs from the training language. The authors also examined
      whether a phone set with contextualization outperforms a more general one. The
      accuracy of two forced aligners trained on English (hmalign and p2fa) was
      assessed using corpus data from Yoloxochitl Mixtec. Overall, agreement
      performance was relatively good, with accuracy at 70.9% within 30 ms for hmalign
      and 65.7% within 30 ms for p2fa. Segmental and tonal categories influenced
      accuracy as well. For instance, additional stop allophones in hmalign's phone set
      aided alignment accuracy. Agreement differences between aligners also
      corresponded closely with the types of data on which the aligners were trained.
      Overall, using existing alignment systems was found to have potential for making
      phonetic analysis of small corpora more efficient, with more allophonic phone
      sets providing better agreement than general ones.

PMID- 23967954
TI  - The clarinet: how blowing pressure, lip force, lip position and reed "hardness"
      affect pitch, sound level, and spectrum.
AB  - Using an automated clarinet playing system, the frequency f, sound level L, and
      spectral characteristics are measured as functions of blowing pressure P and the
      force F applied by the mechanical lip at different places on the reed. The
      playing regime on the (P,F) plane lies below an extinction line F(P) with a
      negative slope of a few square centimeters and above a pressure threshold with a
      more negative slope. Lower values of F and P can produce squeaks. Over much of
      the playing regime, lines of equal frequency have negative slope. This is
      qualitatively consistent with passive reed behavior: Increasing F or P gradually
      closes the reed, reducing its equivalent acoustic compliance, which increases the
      frequency of the peaks of the parallel impedance of bore and reed. High P and low
      F produce the highest sound levels and stronger higher harmonics. At low P, sound
      level can be increased at constant frequency by increasing P while simultaneously
      decreasing F. At high P, where lines of equal f and of equal L are nearly
      parallel, this compensation is less effective. Applying F further from the
      mouthpiece tip moves the playing regime to higher F and P, as does a stiffer
      reed. 

PMID- 23967955
TI  - Preparation of stimuli for timbre perception studies.
AB  - Stimuli used in timbre perception studies must be controlled carefully in order
      to yield meaningful results. During psychoacoustic testing of individual timbre
      properties, (1) it must be ensured that timbre properties do not co-vary, as
      timbre properties are often not independent from one another, and (2) the
      potential influence of loudness, pitch, and perceived duration must be
      eliminated. A mathematical additive synthesis method is proposed which allows
      complete control over two spectral parameters, the spectral centroid
      (corresponding to brightness) and irregularity, and two temporal parameters, log
      rise-time (LRT) and a parameter characterizing the sustain/decay segment, while
      controlling for covariation in the spectral centroid and irregularity. Thirteen
      musical instrument sounds were synthesized. Perceptual data from six listeners
      indicate that variation in the four timbre properties mainly influences loudness
      and that perceived duration and pitch are not influenced significantly for the
      stimuli of longer duration (2 s) used here. Trends across instruments were found
      to be similar.

PMID- 23967956
TI  - Understanding the intentional acoustic behavior of humpback whales: a production
      based approach.
AB  - Following a production-based approach, this paper deals with the acoustic
      behavior of humpback whales. This approach investigates various physical factors,
      which are either internal (e.g., physiological mechanisms) or external (e.g.,
      environmental constraints) to the respiratory tractus of the whale, for their
      implications in sound production. This paper aims to describe a functional
      scenario of this tractus for the generation of vocal sounds. To do so, a division
      of this tractus into three different configurations is proposed, based on the air
      recirculation process which determines air sources and laryngeal valves. Then,
      assuming a vocal function (in sound generation or modification) for several
      specific anatomical components, an acoustic characterization of each of these
      configurations is proposed to link different spectral features, namely,
      fundamental frequencies and formant structures, to specific vocal production
      mechanisms. A discussion around the question of whether the whale is able to
      fully exploit the acoustic potential of its respiratory tractus is eventually
      provided. 

PMID- 23967957
TI  - Discrimination of mixed-directional whistles by a bottlenose dolphin (Tursiops
      truncatus).
AB  - Dolphins are hypothesized to deduce the swimming direction of group members by
      attending to the spectral pattern of whistle harmonics. This is known as the
      direction of movement cue hypothesis and may facilitate coordination of complex
      group behavior when visibility is poor. The direction of movement cue hypothesis
      hinges on the assumption that dolphins can discriminate between whistles with
      different harmonic patterns that are associated with signaler orientation. This
      assumption was tested with a bottlenose dolphin. Whistles were recorded from a
      dolphin at different azimuth positions (0 degrees  to 180 degrees  in 45 degrees 
      increments). Noise-free, synthetic whistles were created to mimic the direction
      dependant spectral profiles of the recorded whistles. A dolphin was then tested
      in its ability to discriminate between the synthetic whistles using fixed level
      and roving level conditions. The dolphin's discrimination performance in both the
      fixed and roving level conditions was near 100% for whistles separated by angles
      greater than 45 degrees , and near chance for 45 degrees  separations. Computer
      simulations of the task, along with the dolphin's performance, suggest that the
      dolphin's discrimination was level invariant and based on the spectral pattern of
      the whistles. 

PMID- 23967958
TI  - Hearing frequency thresholds of a harbor porpoise (Phocoena phocoena) temporarily
      affected by a continuous 1.5 kHz tone.
AB  - Harbor porpoises may suffer hearing loss when exposed to intense sounds. After
      exposure to a 1.5 kHz continuous tone without harmonics at a mean received sound
      pressure level of 154 dB re 1 MUPa for 60 min (cumulative sound exposure level:
      190 dB re 1 MUPa(2) s), the temporary hearing threshold shift (TTS) of a porpoise
      was quantified at 1.5, 2, 4, 6.5, 8, 16, 32, 63, and 125 kHz with a
      psychoacoustic technique. Significant TTS only occurred at 1.5 and 2 kHz. Mean
      TTS (1-4 min after sound exposure stopped) was ~14 dB at 1.5 kHz and ~11 dB at 2
      kHz, and recovery occurred within 96 min. Control hearing tests before and after
      a 60 min low ambient noise exposure showed that normal variation in TTS was
      limited (standard deviation: +/- 1.0 dB). Ecological effects of TTS depend not
      only on the magnitude of the TTS, its duration (depending on the exposure
      duration), and the recovery time after the exposure stopped, but also on the
      hearing frequency affected by the fatiguing noise. The hearing thresholds of
      harbor porpoises for the frequencies of their echolocation signals are not
      affected by intense low frequency sounds, therefore these sounds are unlikely to
      affect foraging efficiency.

PMID- 23967959
TI  - Species-specific beaked whale echolocation signals.
AB  - Beaked whale echolocation signals are mostly frequency-modulated (FM) upsweep
      pulses and appear to be species specific. Evolutionary processes of niche
      separation may have driven differentiation of beaked whale signals used for
      spatial orientation and foraging. FM pulses of eight species of beaked whales
      were identified, as well as five distinct pulse types of unknown species, but
      presumed to be from beaked whales. Current evidence suggests these five distinct
      but unidentified FM pulse types are also species-specific and are each produced
      by a separate species. There may be a relationship between adult body length and
      center frequency with smaller whales producing higher frequency signals. This
      could be due to anatomical and physiological restraints or it could be an
      evolutionary adaption for detection of smaller prey for smaller whales with
      higher resolution using higher frequencies. The disadvantage of higher
      frequencies is a shorter detection range. Whales echolocating with the highest
      frequencies, or broadband, likely lower source level signals also use a higher
      repetition rate, which might compensate for the shorter detection range. Habitat
      modeling with acoustic detections should give further insights into how niches
      and prey may have shaped species-specific FM pulse types. 

PMID- 23967960
TI  - Hearing thresholds of a harbor porpoise (Phocoena phocoena) for playbacks of
      multiple pile driving strike sounds.
AB  - Pile driving is presently the most common method used to attach wind turbines to
      the sea bed. To assess the impact of pile driving sounds on harbor porpoises, it
      is important to know at what distance these sounds can be detected. Using a
      psychophysical technique, a male porpoise's hearing thresholds were obtained for
      series of five pile driving sounds (inter-pulse interval 1.2-1.3 s) recorded at
      100 and 800 m from the pile driving site, and played back in a pool. The 50%
      detection threshold sound exposure levels (SELs) for the first sound of the
      series (no masking) were 72 (100 m) and 74 (800 m) dB re 1 MUPa(2)s. Multiple
      sounds in succession (series) caused a ~5 dB decrease in hearing threshold; the
      mean 50% detection threshold SELs for any sound in the series were 68 (100 m) and
      69 (800 m) dB re 1 MUPa(2)s. Depending on the actual propagation conditions and
      background noise levels, the results suggest that pile driving sounds are audible
      to porpoises at least at tens of kilometers from pile driving sites.

PMID- 23967961
TI  - Hearing thresholds of two harbor seals (Phoca vitulina) for playbacks of multiple
      pile driving strike sounds.
AB  - Pile driving, which creates high amplitude sounds with potentially negative
      impacts on the marine environment, is used to attach wind turbines to the sea
      bed. To quantify the distance at which pile driving sounds can be detected by
      harbor seals, unmasked hearing thresholds were obtained for series of five pile
      driving sounds recorded at 100 and 800 m from a pile driving location. The played
      back spectra resembled the spectra of sounds recorded under certain conditions 10
      50 km from an offshore pile driving site. The lower the received level, the later
      within the series of sounds the harbor seals responded. The mean 50% detection
      threshold sound exposure levels for any sound in the series were: 40 (seal 01,
      100 m), 39 (seal 01, 800 m), 43 (seal 02, 100 m), and 43 (seal 02, 800 m) dB re 1
      MUPa(2)s (add 9 dB for sound pressure level, dB re 1 MUPa). The mean 50%
      detection thresholds based on detection of only the first sound of the series
      were ca. 5 dB higher. Detection at sea depends on the actual propagation
      conditions and on the degree of masking of the sounds by ambient noise, but the
      present study suggests that pile driving sounds are audible to harbor seals up to
      hundreds of kilometers from pile driving sites. 

PMID- 23967962
TI  - Methods for reverberation suppression utilizing dual frequency band imaging.
AB  - Reverberations impair the contrast resolution of diagnostic ultrasound images.
      Tissue harmonic imaging is a common method to reduce these artifacts, but does
      not remove all reverberations. Dual frequency band imaging (DBI), utilizing a low
      frequency pulse which manipulates propagation of the high frequency imaging
      pulse, has been proposed earlier for reverberation suppression. This article adds
      two different methods for reverberation suppression with DBI: the delay corrected
      subtraction (DCS) and the first order content weighting (FOCW) method. Both
      methods utilize the propagation delay of the imaging pulse of two transmissions
      with alternating manipulation pressure to extract information about its depth of
      first scattering. FOCW further utilizes this information to estimate the content
      of first order scattering in the received signal. Initial evaluation is presented
      where both methods are applied to simulated and in vivo data. Both methods yield
      visual and measurable substantial improvement in image contrast. Comparing DCS
      with FOCW, DCS produces sharper images and retains more details while FOCW
      achieves best suppression levels and, thus, highest image contrast. The measured
      improvement in contrast ranges from 8 to 27 dB for DCS and from 4 dB up to the
      dynamic range for FOCW.

PMID- 23967963
TI  - Orangutan (Pongo spp.) whistling and implications for the emergence of an open
      ended call repertoire: a replication and extension.
AB  - One of the most apparent discontinuities between non-human primate (primate) call
      communication and human speech concerns repertoire size. The former is
      essentially fixed to a limited number of innate calls, while the latter
      essentially consists of numerous learned components. Consequently, primates are
      thought to lack laryngeal control required to produce learned voiced calls.
      However, whether they may produce learned voiceless calls awaits investigation.
      Here, a case of voiceless call learning in primates is investigated--orangutan
      (Pongo spp.) whistling. In this study, all known whistling orangutans are
      inventoried, whistling-matching tests (previously conducted with one individual)
      are replicated with another individual using original test paradigms, and
      articulatory and acoustic whistle characteristics are compared between three
      orangutans. Results show that whistling has been reported for ten captive
      orangutans. The test orangutan correctly matched human whistles with
      significantly high levels of performance. Whistle variation between individuals
      indicated voluntary control over the upper lip, lower lip, and respiratory
      musculature, allowing individuals to produce learned voiceless calls. Results are
      consistent with inter- and intra-specific social transmission in whistling
      orangutans. Voiceless call learning in orangutans implies that some important
      components of human speech learning and control were in place before the
      homininae-ponginae evolutionary split.

PMID- 23968034
TI  - Introduction to the special issue on methods for marine mammal passive acoustics.

PMID- 23968035
TI  - Methods for tracking multiple marine mammals with wide-baseline passive acoustic
      arrays.
AB  - Most methods used to track marine mammals with passive acoustics require that
      time differences of arrivals (TDOAs) are established and are associated between
      hydrophone pairs. Consequently, multiple animal trackers commonly apply single
      animal TDOA localization methods after performing a call separation and/or TDOA
      association step. When a wide-baseline array is used with multiple animals that
      make similar calls with short inter-call-intervals, the separation/association
      step can be challenging and potentially rejects valid TDOAs. This paper extends a
      model-based TDOA method to deal with multiple-animal datasets in a way that does
      not require a TDOA association step; animals are separated based on position.
      Advantageously, false TDOAs (e.g., a direct path associated with a multipath
      arrival) do not need to be removed. An analogous development is also presented
      for a model-based time of arrival tracking method. Results from simulations and
      application to a multiple sperm whale dataset are used to illustrate the multiple
      animal methods. Although computationally more demanding than most track-after
      association methods because separation is performed in a higher-dimensional
      space, the methods are computationally tractable and represent a useful new tool
      in the suite of options available for tracking multiple animals with passive
      acoustics. 

PMID- 23968036
TI  - Effects of different analysis techniques and recording duty cycles on passive
      acoustic monitoring of killer whales.
AB  - Killer whales in British Columbia are at risk, and little is known about their
      winter distribution. Passive acoustic monitoring of their year-round habitat is a
      valuable supplemental method to traditional visual and photographic surveys.
      However, long-term acoustic studies of odontocetes have some limitations,
      including the generation of large amounts of data that require highly time
      consuming processing. There is a need to develop tools and protocols to maximize
      the efficiency of such studies. Here, two types of analysis, real-time and long
      term spectral averages, were compared to assess their performance at detecting
      killer whale calls in long-term acoustic recordings. In addition, two different
      duty cycles, 1/3 and 2/3, were tested. Both the use of long term spectral
      averages and a lower duty cycle resulted in a decrease in call detection and
      positive pod identification, leading to underestimations of the amount of time
      the whales were present. The impact of these limitations should be considered in
      future killer whale acoustic surveys. A compromise between a lower resolution
      data processing method and a higher duty cycle is suggested for maximum
      methodological efficiency. 

PMID- 23968037
TI  - A practical weighting function for harbor porpoise underwater sound level
      measurements.
AB  - Harbor porpoise (Phocoena phocoena) are subject to underwater noise disturbance
      from anthropogenic sources, especially shipping. The underwater audiograms of
      harbor porpoise were used to create a frequency weighting function, dBht(Phocoena
      phocoena), to permit estimation of the broadband perceived amplitudes of ambient
      and shipping noise. An equation was fit to the 0.02-20 kHz range of unmasked
      detection thresholds and normalizing to 0 dB at 20 kHz; dB = 46.4-35.6 log(kHz).
      The weighting function de-emphasizes the low frequency components of noise.
      Harbor porpoise hearing is less sensitive to low frequency shipping noise and,
      except at high amplitudes, estimating potential noise impacts using linear
      measurements will be misleading.

PMID- 23968038
TI  - Effect of towed array stability on instantaneous localization of marine mammals.
AB  - Reliable localization of marine mammals using towed arrays is often required for
      mitigation, population density estimates, and bioacoustics research. The accuracy
      of the range estimates using towed arrays is often not well quantified.
      Triangulation methods using multiple hydrophones allow for fast range estimates
      but are sensitive to the species type, location of the animal with respect to the
      array, sound propagation conditions, and array stability. A simple model is
      presented that is used to estimate the range accuracy of towed arrays for
      different vocalizations and is compared to measured range accuracies of sperm
      whale clicks recorded with a 15 m baseline towed array. The ranging performance
      is particularly sensitive to hydrophone position errors which are found to
      dominate. Hydrophone position errors could be estimated using heading sensors
      placed in the array and are taken into account in the model. A good agreement is
      found between the empirical range errors and theoretically predicted ones.
      Extrapolation of the model to other species suggests that species emitting high
      frequency clicks and calls can be localized from distances out to a few
      kilometers with a baseline of 15 m, but baleen whales transmitting low frequency
      calls require longer baselines to obtain range estimates.

PMID- 23968039
TI  - A multimodal detection model of dolphins to estimate abundance validated by field
      experiments.
AB  - Abundance estimation of marine mammals requires matching of detection of an
      animal or a group of animal by two independent means. A multimodal detection
      model using visual and acoustic cues (surfacing and phonation) that enables
      abundance estimation of dolphins is proposed. The method does not require a
      specific time window to match the cues of both means for applying mark-recapture
      method. The proposed model was evaluated using data obtained in field
      observations of Ganges River dolphins and Irrawaddy dolphins, as examples of
      dispersed and condensed distributions of animals, respectively. The acoustic
      detection probability was approximately 80%, 20% higher than that of visual
      detection for both species, regardless of the distribution of the animals in
      present study sites. The abundance estimates of Ganges River dolphins and
      Irrawaddy dolphins fairly agreed with the numbers reported in previous monitoring
      studies. The single animal detection probability was smaller than that of larger
      cluster size, as predicted by the model and confirmed by field data. However,
      dense groups of Irrawaddy dolphins showed difference in cluster sizes observed by
      visual and acoustic methods. Lower detection probability of single clusters of
      this species seemed to be caused by the clumped distribution of this species. 

PMID- 23968040
TI  - Automatic detection and classification of odontocete whistles.
AB  - Methods for the fully automatic detection and species classification of
      odontocete whistles are described. The detector applies a number of noise
      cancellation techniques to a spectrogram of sound data and then searches for
      connected regions of data which rise above a pre-determined threshold. When
      tested on a dataset of recordings which had been carefully annotated by a human
      operator, the detector was able to detect (recall) 79.6% of human identified
      sounds that had a signal-to-noise ratio above 10 dB, with 88% of the detections
      being valid. A significant problem with automatic detectors is that they tend to
      partially detect whistles or break whistles into several parts. A classifier has
      been developed specifically to work with fragmented whistle detections. By
      accumulating statistics over many whistle fragments, correct classification rates
      of over 94% have been achieved for four species. The success rate is, however,
      heavily dependent on the number of species included in the classifier mix, with
      the mean correct classification rate dropping to 58.5% when 12 species were
      included.

PMID- 23968041
TI  - Acoustically derived growth rates of sperm whales (Physeter macrocephalus) in
      Kaikoura, New Zealand.
AB  - A non-invasive acoustic method for measuring the growth of sperm whales was
      developed based on estimating the length of individuals by measuring the inter
      pulse interval (IPI) of their clicks. Most prior knowledge of growth in male
      sperm whales has come from from fitting growth curves to length data gained from
      whaling. Recordings made at Kaikoura, New Zealand, were used to estimate the
      length and growth of 32 photographically identified, resident whales that have
      been recorded repeatedly between 1991 and 2009. All whales recorded more than six
      months apart (n = 30) showed an increase in IPI. Using established relationships
      between IPI and total length, it was found that the average growth rate in the
      Kaikoura population is lower, especially for smaller whales (13-14.5 m), than
      that derived from historical whaling data from other populations. This difference
      may be due to ecological differences among populations but might also reflect
      upward bias in measurements gained in whaling. The ability to track growth of
      individuals through time is only possible via non-lethal means and offers a
      fundamentally different kind of data because differences among individuals can be
      measured.

PMID- 23968042
TI  - Acoustic tracking of sperm whales in the Gulf of Alaska using a two-element
      vertical array and tags.
AB  - Between 15 and 17 August 2010, a simple two-element vertical array was deployed
      off the continental slope of Southeast Alaska in 1200 m water depth. The array
      was attached to a vertical buoy line used to mark each end of a longline fishing
      set, at 300 m depth, close to the sound-speed minimum of the deep-water profile.
      The buoy line also served as a depredation decoy, attracting seven sperm whales
      to the area. One animal was tagged with both a LIMPET dive depth-transmitting
      satellite and bioacoustic "B-probe" tag. Both tag datasets were used as an
      independent check of various passive acoustic schemes for tracking the whale in
      depth and range, which exploited the elevation angles and relative arrival times
      of multiple ray paths recorded on the array. Analytical tracking formulas were
      viable up to 2 km range, but only numerical propagation models yielded accurate
      locations up to at least 35 km range at Beaufort sea state 3. Neither
      localization approach required knowledge of the local bottom bathymetry. The
      tracking system was successfully used to estimate the source level of an
      individual sperm whale's "clicks" and "creaks" and predict the maximum detection
      range of the signals as a function of sea state.

PMID- 23968043
TI  - Determining the detection thresholds for harbor porpoise clicks of autonomous
      data loggers, the Timing Porpoise Detectors.
AB  - Timing Porpoise Detectors (T-PODs, Chelonia Ltd.) are autonomous passive acoustic
      devices for monitoring odontocetes. They register the time of occurrence and
      duration of high frequency pulsed sounds as possible odontocetes echolocation
      clicks. Because of evolution, five T-POD versions exist. Although the
      manufacturer replaced those by a digital successor, the C-POD, T-PODs are still
      used, and data from many field studies exist. Characterizing the acoustic
      properties of T-PODs enables the interpretation of data obtained with different
      devices. Here, the detection thresholds of different T-POD versions for harbor
      porpoise clicks were determined. While thresholds among devices were quite
      variable in the first T-POD generations, they became more standardized in newer
      versions. Furthermore, the influence of user-controlled settings on the threshold
      was investigated. From version 3 on, the detection threshold was found to be
      easily adjustable with version-dependent setting options "minimum intensity" and
      "sensitivity," enabling the presetting of standard thresholds. In version 4, the
      setting "click bandwidth" had a strong influence on the detection threshold,
      while "selectivity" in version 3 and "noise adaptation = ON" or "OFF" in version
      4 hardly influenced thresholds obtained in the tank tests. Nevertheless, the
      latter setting may influence thresholds in a complex acoustic environment like
      the sea. 

PMID- 23968044
TI  - The effects of acoustic misclassification on cetacean species abundance
      estimation.
AB  - To estimate the density or abundance of a cetacean species using acoustic
      detection data, it is necessary to correctly identify the species that are
      detected. Developing an automated species classifier with 100% correct
      classification rate for any species is likely to stay out of reach. It is
      therefore necessary to consider the effect of misidentified detections on the
      number of observed data and consequently on abundance or density estimation, and
      develop methods to cope with these misidentifications. If misclassification rates
      are known, it is possible to estimate the true numbers of detected calls without
      bias. However, misclassification and uncertainties in the level of
      misclassification increase the variance of the estimates. If the true numbers of
      calls from different species are similar, then a small amount of
      misclassification between species and a small amount of uncertainty around the
      classification probabilities does not have an overly detrimental effect on the
      overall variance. However, if there is a difference in the encounter rate between
      species calls and/or a large amount of uncertainty in misclassification rates,
      then the variance of the estimates becomes very large and this dramatically
      increases the variance of the final abundance estimate. 

PMID- 23968045
TI  - An automatic detection algorithm for extracting the representative frequency of
      cetacean tonal sounds.
AB  - Most studies on tonal sounds extract contour parameters from fundamental
      frequencies. The presence of harmonics and the frequency distribution of multiple
      tonal sounds have not been well researched. To investigate the occurrence and
      frequency modulation of cetacean tonal sounds, the procedure of detecting the
      instantaneous frequency bandwidth of tonal spectral peaks was integrated within
      the local-max detector to extract adopted frequencies. The adopted frequencies,
      considered the representative frequencies of tonal sounds, are used to find the
      presence of harmonics and overlapping tonal sounds. The utility and detection
      performance are demonstrated on acoustic recordings of five species from two
      databases. The recordings of humpback dolphins showed a 75% detection rate with a
      5% false detection rate, and recordings from the MobySound archive showed an 85%
      detection rate with a 5% false detection rate. These detections were achieved in
      signal-to-noise ratios of -12 to 21 dB. The parameters that measured the
      distribution of adopted frequency, as well as the prominence of harmonics and
      overlaps, indicate that the modulation of tonal sounds varied among different
      species and behaviors. This algorithm can be applied to studies on cetacean
      communication signals and long-term passive acoustic monitoring.

PMID- 23968046
TI  - Trackline and point detection probabilities for acoustic surveys of Cuvier's and
      Blainville's beaked whales.
AB  - Acoustic survey methods can be used to estimate density and abundance using
      sounds produced by cetaceans and detected using hydrophones if the probability of
      detection can be estimated. For passive acoustic surveys, probability of
      detection at zero horizontal distance from a sensor, commonly called g(0),
      depends on the temporal patterns of vocalizations. Methods to estimate g(0) are
      developed based on the assumption that a beaked whale will be detected if it is
      producing regular echolocation clicks directly under or above a hydrophone. Data
      from acoustic recording tags placed on two species of beaked whales (Cuvier's
      beaked whale-Ziphius cavirostris and Blainville's beaked whale-Mesoplodon
      densirostris) are used to directly estimate the percentage of time they produce
      echolocation clicks. A model of vocal behavior for these species as a function of
      their diving behavior is applied to other types of dive data (from time-depth
      recorders and time-depth-transmitting satellite tags) to indirectly determine
      g(0) in other locations for low ambient noise conditions. Estimates of g(0) for a
      single instant in time are 0.28 [standard deviation (s.d.) = 0.05] for Cuvier's
      beaked whale and 0.19 (s.d. = 0.01) for Blainville's beaked whale. 

PMID- 23968047
TI  - Passive acoustic monitoring of Cook Inlet beluga whales (Delphinapterus leucas).
AB  - The endangered beluga whale (Delphinapterus leucas) population in Cook Inlet, AK
      faces threats from a variety of anthropogenic factors, including coastal
      development, oil and gas exploration, vessel traffic, and military activities. To
      address existing gaps in understanding about the occurrence of belugas in Cook
      Inlet, a project was developed to use passive acoustic monitoring to document the
      year-round distribution of belugas, as well as killer whales (Orcinus orca),
      which prey on belugas. Beginning in June 2009, ten moorings were deployed
      throughout the Inlet and refurbished every two to eight months. Despite
      challenging conditions consisting of strong tidal currents carrying debris and
      seasonal ice cover, 83% of mooring deployments were successfully recovered. Noise
      from water flow, vessel traffic, and/or industrial activities was present at
      several sites, potentially masking some signals. However, belugas were
      successfully detected at multiple locations. Detections were relatively common in
      the upper inlet and less common or absent at middle and lower inlet locations.
      Killer whale signals were also recorded. Some seasonal variability in the
      occurrence of both belugas and killer whales was evident. 

PMID- 23968048
TI  - Acoustic detection and long-term monitoring of pygmy blue whales over the
      continental slope in southwest Australia.
AB  - A 9-yr dataset of continuous sea noise recording made at the Cape Leeuwin station
      of the Comprehensive Nuclear-Test-Ban Treaty hydroacoustic network in 2002-2010
      was processed to detect calls from pygmy blue whales and to analyze diurnal,
      seasonal, and interannual variations in their vocal activity. Because the
      conventional spectrogram correlation method for recognizing whale calls in sea
      noise resulted in a too high false detection rate, alternative algorithms were
      tested and the most robust one applied to the multi-year dataset. The detection
      method was based on multivariate classification using two spectrogram features of
      transients in sea noise and Fisher's linear discriminant, which provided a
      misclassification rate of approximately 1% for missed and false detections at
      moderate sensitivity settings. An analysis of the detection results revealed a
      consistent seasonal pattern in the whale presence and considerable interannual
      changes with a steady increase in the number of calls detected in 2002-2006. An
      apparent diurnal pattern of whales' vocal activity was also observed. The
      acoustic detection range for pygmy blue whales was estimated to vary from about
      50 km to nearly 200 km from the Cape Leeuwin station, depending on the ambient
      noise level, source level, and azimuth to a vocalizing whale.

PMID- 23968049
TI  - Methodology and results of calibration of tonal click detectors for small
      odontocetes (C-PODs).
AB  - Static acoustic monitoring (SAM) is one major technology for observing small
      cetacean species. Automatic click loggers deployed for long time periods (>2
      months) with a single hydrophone are a standard solution. Acoustic properties,
      like detection thresholds of these instruments, are essential for interpretation
      of results, but have nevertheless received little attention. A methodology for
      calibrating tonal click detectors in small tanks consisting of the determination
      of the horizontal directivity pattern and detection thresholds including a
      transfer function is presented. Two approaches were tested to determine detection
      thresholds by (a) determining the 50% detection threshold and (b) fitting a
      linear regression model to the recorded relative amplitudes. The tests were
      carried out on C-PODs (Cetacean PODs, tonal click detectors), the most commonly
      used instrument for SAM in Europe. Directivity and threshold were tested between
      60 and 150 kHz. Directivity showed a maximum variation of 8.5 dB in the
      horizontal plane. Sensitivity is highest between 80 and 130 kHz and linear (+/- 3
      dB) in this frequency range for most of the instruments tested. C-PODs have a
      detection threshold (calculated with the linear model) of 114.5 +/- 1.2 (standard
      deviation) dB re 1 MUPa peak-peak at 130 kHz.

PMID- 23968050
TI  - Predictions from harbor porpoise habitat association models are confirmed by long
      term passive acoustic monitoring.
AB  - Survey based habitat association models provide good spatial coverage, but only a
      snapshot in time of a species' occurrence in a particular area. A habitat
      association model for harbor porpoises was created using data from five visual
      surveys of the Moray Firth, Scotland. Its predictions were tested over broader
      temporal scales using data from static passive acoustic loggers, deployed in two
      consecutive years. Predictions of relative abundance (individuals per kilometer
      of survey transect) were obtained for each 4 km * 4 km grid cell, and compared
      with the median number of hours per day that porpoises were acoustically detected
      in those cells. There was a significant, but weak, correlation between predicted
      relative abundance and acoustic estimates of occurrence, but this was stronger
      when predictions with high standard errors were omitted. When grid cells were
      grouped into those with low, medium, and high predicted relative abundance, there
      were similarly significant differences in acoustic detections, indicating that
      porpoises were acoustically detected more often in cells where the habitat model
      predicted higher numbers. The integration of acoustic and visual data added value
      to the interpretation of results from each, allowing validation of patterns in
      relative abundance recorded during snapshot visual surveys over longer time
      scales.

PMID- 23968051
TI  - Underwater passive acoustic localization of Pacific walruses in the northeastern
      Chukchi Sea.
AB  - This paper develops and applies a linearized Bayesian localization algorithm
      based on acoustic arrival times of marine mammal vocalizations at spatially
      separated receivers which provides three-dimensional (3D) location estimates with
      rigorous uncertainty analysis. To properly account for uncertainty in receiver
      parameters (3D hydrophone locations and synchronization times) and environmental
      parameters (water depth and sound-speed correction), these quantities are treated
      as unknowns constrained by prior estimates and prior uncertainties. Unknown
      scaling factors on both the prior and arrival-time uncertainties are estimated by
      minimizing Akaike's Bayesian information criterion (a maximum entropy condition).
      Maximum a posteriori estimates for sound source locations and times, receiver
      parameters, and environmental parameters are calculated simultaneously using
      measurements of arrival times for direct and interface-reflected acoustic paths.
      Posterior uncertainties for all unknowns incorporate both arrival time and prior
      uncertainties. Monte Carlo simulation results demonstrate that, for the cases
      considered here, linearization errors are small and the lack of an accurate sound
      speed profile does not cause significant biases in the estimated locations. A
      sequence of Pacific walrus vocalizations, recorded in the Chukchi Sea northwest
      of Alaska, is localized using this technique, yielding a track estimate and
      uncertainties with an estimated speed comparable to normal walrus swim speeds. 

PMID- 23968052
TI  - Automated segmentation of linear time-frequency representations of marine-mammal
      sounds.
AB  - Many marine mammals produce highly nonlinear frequency modulations. Determining
      the time-frequency support of these sounds offers various applications, which
      include recognition, localization, and density estimation. This study introduces
      a low parameterized automated spectrogram segmentation method that is based on a
      theoretical probabilistic framework. In the first step, the background noise in
      the spectrogram is fitted with a Chi-squared distribution and thresholded using a
      Neyman-Pearson approach. In the second step, the number of false detections in
      time-frequency regions is modeled as a binomial distribution, and then through a
      Neyman-Pearson strategy, the time-frequency bins are gathered into regions of
      interest. The proposed method is validated on real data of large sequences of
      whistles from common dolphins, collected in the Bay of Biscay (France). The
      proposed method is also compared with two alternative approaches: the first is
      smoothing and thresholding of the spectrogram; the second is thresholding of the
      spectrogram followed by the use of morphological operators to gather the time
      frequency bins and to remove false positives. This method is shown to increase
      the probability of detection for the same probability of false alarms. 

PMID- 23968053
TI  - Site specific probability of passive acoustic detection of humpback whale calls
      from single fixed hydrophones.
AB  - Passive acoustic monitoring of marine mammal calls is an increasingly important
      method for assessing population numbers, distribution, and behavior. A common
      mistake in the analysis of marine mammal acoustic data is formulating conclusions
      about these animals without first understanding how environmental properties such
      as bathymetry, sediment properties, water column sound speed, and ocean acoustic
      noise influence the detection and character of vocalizations in the acoustic
      data. The approach in this paper is to use Monte Carlo simulations with a full
      wave field acoustic propagation model to characterize the site specific
      probability of detection of six types of humpback whale calls at three passive
      acoustic monitoring locations off the California coast. Results show that the
      probability of detection can vary by factors greater than ten when comparing
      detections across locations, or comparing detections at the same location over
      time, due to environmental effects. Effects of uncertainties in the inputs to the
      propagation model are also quantified, and the model accuracy is assessed by
      comparing calling statistics amassed from 24,690 humpback units recorded in the
      month of October 2008. Under certain conditions, the probability of detection can
      be estimated with uncertainties sufficiently small to allow for accurate density
      estimates.

PMID- 23968054
TI  - Calling depths of baleen whales from single sensor data: development of an
      autocorrelation method using multipath localization.
AB  - Multipath localization techniques have not previously been applied to baleen
      whale vocalizations due to difficulties in application to tonal vocalizations.
      Here it is shown that an autocorrelation method coupled with the direct reflected
      time difference of arrival localization technique can successfully resolve
      location information. A derivation was made to model the autocorrelation of a
      direct signal and its overlapping reflections to illustrate that an
      autocorrelation may be used to extract reflection information from longer
      duration signals containing a frequency sweep, such as some calls produced by
      baleen whales. An analysis was performed to characterize the difference in
      behavior of the autocorrelation when applied to call types with varying
      parameters (sweep rate, call duration). The method's feasibility was tested using
      data from playback transmissions to localize an acoustic transducer at a known
      depth and location. The method was then used to estimate the depth and range of a
      single North Atlantic right whale (Eubalaena glacialis) and humpback whale
      (Megaptera novaeangliae) from two separate experiments. 

PMID- 23968055
TI  - Source levels of dugong (Dugong dugon) vocalizations recorded in Shark Bay.
AB  - Dugongs (Dugong dugon) spend significant time in shallow, turbid waters and are
      often active at night, conditions which are not conducive to visual cues. In
      part, as a result, dugongs vocalize to gain or pass information. Passive acoustic
      recording is a useful tool for remote detection of vocal marine animals, but its
      application to dugongs has been little explored compared with other mammals.
      Aerial surveys, often used to monitor dugong distribution and abundance, are not
      always financially or logistically viable and involve inherent availability and
      perception bias considerations. Passive acoustic monitoring is also subject to
      sampling biases and a first step to identifying these biases and understanding
      the detection or communication range of animal calls is to determine call source
      level. In March 2012, four dugongs were fitted with satellite tags in Shark Bay,
      Western Australia by the Department of Environment and Conservation. During this,
      acoustic recordings were taken at 5.1 m range. Source levels for each of five
      call types (two types of chirp, bark, squeak, and quack) were estimated, assuming
      spherical spreading as the transmission loss. Mean source levels for these call
      types were 139 (n = 19), 135 (12), 142 (2), 158 (1), and 136 (9) dB re 1 MUPa at
      1 m, respectively.

PMID- 23968056
TI  - Passive acoustic monitoring using a towed hydrophone array results in
      identification of a previously unknown beaked whale habitat.
AB  - Beaked whales are diverse and species rich taxa. They spend the vast majority of
      their time submerged, regularly diving to depths of hundreds to thousands of
      meters, typically occur in small groups, and behave inconspicuously at the
      surface. These factors make them extremely difficult to detect using standard
      visual survey methods. However, recent advancements in acoustic detection
      capabilities have made passive acoustic monitoring (PAM) a viable alternative.
      Beaked whales can be discriminated from other odontocetes by the unique
      characteristics of their echolocation clicks. In 2009 and 2010, PAM methods using
      towed hydrophone arrays were tested. These methods proved highly effective for
      real-time detection of beaked whales in the Southern California Bight (SCB) and
      were subsequently implemented in 2011 to successfully detect and track beaked
      whales during the ongoing Southern California Behavioral Response Study. The
      three year field effort has resulted in (1) the successful classification and
      tracking of Cuvier's (Ziphius cavirostris), Baird's (Berardius bairdii), and
      unidentified Mesoplodon beaked whale species and (2) the identification of areas
      of previously unknown beaked whale habitat use. Identification of habitat use
      areas will contribute to a better understanding of the complex relationship
      between beaked whale distribution, occurrence, and preferred habitat
      characteristics on a relatively small spatial scale. These findings will also
      provide information that can be used to promote more effective management and
      conservation of beaked whales in the SCB, a heavily used Naval operation and
      training region. 

PMID- 23968057
TI  - Acoustic detection probability of bottlenose dolphins, Tursiops truncatus, with
      static acoustic dataloggers in Cardigan Bay, Wales.
AB  - Acoustic dataloggers are used for monitoring the occurrence of cetaceans and can
      aid in fulfilling statutory monitoring requirements of protected species.
      Although useful for long-term monitoring, their spatial coverage is restricted,
      and for many devices the effective detection distance is not specified. A
      generalized additive mixed model (GAMM) was used to investigate the effects of
      (1) distance from datalogger, (2) animal behavior (feeding and traveling), and
      (3) group size on the detection probability of bottlenose dolphins (Tursiops
      truncatus) with autonomous dataloggers (C-PODs) validated with visual
      observations. The average probability of acoustic detection for minutes with a
      sighting was 0.59 and the maximum detection distance ranged from 1343-1779 m.
      Minutes with feeding activity had higher acoustic detection rates and longer
      average effective detection radius (EDR) than traveling ones. The detection
      probability for single dolphins was significantly higher than for groups,
      indicating that their acoustic behavior may differ from those of larger groups in
      the area, making them more detectable. The C-POD is effective at detecting
      dolphin presence but the effects of behavior and group size on detectability
      create challenges for estimating density from detections as higher detection rate
      of feeding dolphins could yield erroneously high density estimates in feeding
      areas.

PMID- 23968058
TI  - Range estimation of cetaceans with compact volumetric arrays.
AB  - Passive acoustic monitoring is the method of choice to detect whales and dolphins
      that are acoustically active and to monitor their underwater behavior. The NATO
      Science and Technology Organization Centre for Maritime Research and
      Experimentation has recently implemented a compact passive acoustic monitor
      (CPAM), consisting of three arrays of two hydrophones each that are combined in a
      fixed three-dimensional arrangement and that may be towed at depths of more than
      100 m. With its volumetric configuration, the CPAM is capable of estimating the
      three-dimensional direction vector of arriving sounds and under certain
      conditions on relative geometry between the whale and hydrophone array, the CPAM
      may also estimate the range to echolocating animals. Basic ranging methods assume
      constant sound speed and apply straightforward geometry to obtain depth and
      distance to the sound source. Alternatively, ray-tracing based methods may be
      employed to integrate the information provided by real sound speed profiles. Both
      ranging methods combine measurements of sound arrival angles and surface
      reflection delays and are easily implemented in real-time applications, whereby
      one could promote the ray-tracing approach as the preferred method because it may
      integrate real sound speed profiles.

PMID- 23968059
TI  - Ultrasonic measurements of the reflection coefficient at a water/polyurethane
      foam interface.
AB  - Measured ultrasonic reflection coefficients as a function of normal incidence
      angle are reported for several samples of polyurethane foam submerged in a water
      bath. Three reflection coefficient models are employed as needed in this analysis
      to approximate the measured data: (1) an infinite plane wave impinging on an
      elastic halfspace, (2) an infinite plane wave impinging on a single fluid layer
      overlying a fluid halfspace, and (3) a finite acoustic beam impinging on an
      elastic halfspace. The compressional wave speed in each sample is calculated by
      minimizing the sum of squared error (SSE) between the measured and modeled data. 

PMID- 23968060
TI  - Feasibility of a high-powered carbon nanotube thin-film loudspeaker.
AB  - The thermophone, conceived in 1917 by Arnold and Crandall, was a unique
      thermoacoustic loudspeaker. The high heat capacity per unit area (HCPUA) of thin
      film materials at that time limited the usefulness of thermophones. Recently,
      researchers of carbon nanotubes (CNTs) have developed techniques to create a
      super-aligned thin-film of multi-walled CNTs, possessing extremely low HCPUA.
      This paper will discuss CNT thin-film loudspeaker theory as well as some initial
      investigations into the feasibility of a high-powered audio CNT speaker. The
      advantages of such a loudspeaker include: Ultra-lightweight, compact, no moving
      parts, low cost, and independence from expensive rare-earth materials. 

PMID- 23968061
TI  - The robustness of speech representations obtained from simulated auditory nerve
      fibers under different noise conditions.
AB  - Different methods of extracting speech features from an auditory model were
      systematically investigated in terms of their robustness to different noises. The
      methods either computed the average firing rate within frequency channels
      (spectral features) or inter-spike-intervals (timing features) from the simulated
      auditory nerve response. When used as the front-end for an automatic speech
      recognizer, timing features outperformed spectral features in Gaussian noise.
      However, this advantage was lost in babble, because timing features extracted the
      spectro-temporal structure of babble noise, which is similar to the target
      speaker. This suggests that different feature extraction methods are optimal
      depending on the background noise. 

PMID- 23968062
TI  - Communication: Electronic UV-Vis transient spectra of the ?OH reaction products
      of uracil, thymine, cytosine, and 5,6-dihydrouracil by using the complete active
      space self-consistent field second-order perturbation (CASPT2//CASSCF) theory.
AB  - Addition of ?OH radicals to pyrimidine nucleobases is a common reaction in
      DNA/RNA damage by reactive oxygen species. Among several experimental techniques,
      transient absorption spectroscopy has been during the last decades used to
      characterize such compounds. Discrepancies have however appeared in the
      assignment of the adduct or adducts responsible for the reported transient
      absorption UV-Vis spectra. In order to get an accurate assignment of the
      transient spectra and a unified description of the absorption properties of the
      ?OH reaction products of pyrimidines, a systematic complete active space self
      consistent field second-order perturbation (CASPT2//CASSCF) theory study has been
      carried out on the uracil, thymine, and cytosine ?OH addition adducts, as well as
      on the 5,6-dihydrouracil hydrogen abstraction products. With the obtained
      findings, the C5OH contributions to the lowest-energy band can be finally
      discarded. Instead, a bright (2)(pi2) state of the C6OH adducts is determined to
      be the main responsible in all compounds for the absorption band in the Vis
      range.

PMID- 23968063
TI  - Communication: Infrared spectroscopy of protonated allyl-trimethylsilane:
      Evidence for the beta-silyl effect.
AB  - beta-trimethylsilyl-2-propyl cation has been formed by the gas phase protonation
      of allyl-trimethylsilane and characterized by infrared multiple photon
      dissociation spectroscopy. The experimental Cbeta-Calpha (+) stretching feature
      at 1586 cm(-1), remarkably blue-shifted with respect to a C-C single bond
      stretching mode, is indicative of high double bond character, a signature of beta
      stabilizing effect due to hyperconjugation of the trimethylsilyl group in the
      beta-position with respect to the positively charged carbon. Density functional
      theory calculations at the B3LYP/6-311++G(2df,2p) level yield the optimized
      geometries and IR spectra for candidate isomeric cations and for neutral and
      charged reference species. 

PMID- 23968064
TI  - Communication: An approximation to Bader's topological atom.
AB  - A new, more flexible definition of fuzzy Voronoi cells is proposed as a
      computationally efficient alternative to Bader's Quantum Theory of Atoms in
      Molecules (QTAIM) partitioning of the physical space for large-scale routine
      calculations. The new fuzzy scheme provides atomic charges, delocalization
      indices, and molecular energy components very close to those obtained using
      QTAIM. The method is flexible enough to either ignore the presence of spurious
      non-nuclear attractors or to readily incorporate them by introducing additional
      fuzzy Voronoi cells. 

PMID- 23968065
TI  - Communication: Autodetachment versus internal conversion from the S1 state of the
      isolated GFP chromophore anion.
AB  - The anionic form of p-hydroxybenzylidene-2,3-dimethylimidazolinone (HBDI) has
      been extensively employed as a model of the chromophore of the green fluorescence
      protein. The bright S1 excited state HBDI(-) has a measured lifetime of 1.4 ps in
      the gas-phase and is dominated by two non-radiative decay mechanisms: internal
      conversion and autodetachment into the neutral continuum. Here, time-resolved
      photoelectron spectroscopy has been used to determine the yields of these two
      channels from which the lifetime for autodetachment was found to be ~30 ps. 

PMID- 23968066
TI  - Structural cluster analysis of chemical reactions in solution.
AB  - We introduce a simple and general approach to the problem of clustering
      structures from atomic trajectories of chemical reactions in solution. By
      considering distance metrics which are invariant under permutation of identical
      atoms or molecules, we demonstrate that it is possible to automatically resolve
      as distinct structural clusters the configurations corresponding to reactants,
      products, and transition states, even in presence of atom-exchanges and of
      hundreds of solvent molecules. Our approach strongly simplifies the analysis of
      large trajectories and it opens the way to the construction of kinetic network
      models of activated processes in solution employing the available efficient
      schemes developed for proteins conformational ensembles. 

PMID- 23968067
TI  - Reducing the propensity for unphysical wavefunction symmetry breaking in
      multireference calculations of the excited states of semiconductor clusters.
AB  - Unphysical spatial symmetry breaking in multiconfigurational self-consistent
      field calculations can lead to undesirable artifacts in the potential energy
      surfaces and electronic properties of molecules. Herein, we report several
      examples of such symmetry breaking in calculations of the excited states of small
      semiconductor clusters and related molecules at the state-averaged complete
      active space self-consistent field (SA-CASSCF) level of theory. A multireference
      approach is proposed to reduce its incidence: the singly excited active space
      complete active space configuration interaction (SEAS-CASCI) method. In SEAS
      CASCI, the orbitals are determined by variationally minimizing an energy
      expression that does not depend on the off-diagonal Hamiltonian matrix elements
      which drive symmetry breaking at the SA-CASSCF level of theory. By application to
      several highly symmetric molecules, SEAS-CASCI is demonstrated to reduce the
      propensity for unphysical spatial symmetry breaking and eliminate resulting
      errors in the potential energy surfaces and molecular properties relative to the
      SA-CASSCF description. The SEAS method is also found to eliminate unphysical
      wavefunction distortion in asymmetric molecules. Finally, SEAS-CASCI is
      demonstrated to accurately describe the biradicaloid region of the potential
      energy surface of ethylene. 

PMID- 23968068
TI  - Direct evaluation of the position dependent diffusion coefficient and persistence
      time from the equilibrium density profile in anisotropic fluids.
AB  - We derive expressions for the transverse diffusion coefficient D(z) and the
      average persistence time tau(z; L) within a layer of width L, for particles of a
      non-homogeneous fluid enclosed in a planar nanopore. The method allows the direct
      evaluation of these position-dependent dynamical quantities from the equilibrium
      local particle density profile. We use results for the density and persistence
      time profiles from the virtual layer molecular dynamics method to numerically
      assess the significance of the Smoluchowski approximation.

PMID- 23968069
TI  - A new perturbed-chain equation of state for square-well chains in fluid and solid
      phases.
AB  - Considering the hard-chain system as reference, a perturbed-chain equation of
      state (EOS) is developed. The second-order thermodynamic perturbation theory EOS
      is applied to the reference system. Monte Carlo simulation data for average intra
      molecular and inter-molecular segment-segment radial distribution function of
      hard-chain systems with a chain length of 3-10 in the range of packing fraction
      between 0.1 and 0.72, covering both fluid and solid phases, are reported. A
      disordered solid phase structure is considered in this work. These customized
      data are used to develop the perturbation term of square-well (SW) attractions.
      The performance of perturbed-chain EOS is tested against computer simulation data
      from the literature for compressibility factor and phase equilibrium in the
      systems of SW chains. Results within good accuracy are obtained for all the test
      cases. Global vapor-liquid-solid equilibrium diagrams for SW chain systems
      predicted by the new EOS are reported. 

PMID- 23968070
TI  - Non-Born-Oppenheimer potential energy curve: Hydrogen molecular ion with highly
      accurate free complement method.
AB  - Although the concept of a potential energy curve (PEC) originates from the
      outgrowth of the Born-Oppenheimer (BO) approximation, we propose the application
      of analysis methods for the physical PEC with non-Born-Oppenheimer (non-BO) wave
      functions. A numerical examination was performed with the highly accurate non-BO
      vibronic wave functions of hydrogen molecular ion, which were obtained in our
      previous studies with the free complement method. The reduced density function
      integrated over the electron coordinates plays an important role in understanding
      nuclear motion dynamics, since it corresponds to the wave function density of the
      vibrational and rotational motions. The maximum positions of this density
      indicate the high existence probability of nuclei and can be considered as a
      discrete representation of the PEC. Whereas an ordinary PEC with the BO
      approximation is obtained as a numeric curve after multiple electronic state
      calculations at fixed nuclear coordinates, we propose a new analytical expression
      of the PEC from a non-BO wave function. 

PMID- 23968071
TI  - Single string based global optimizer for geometry optimization in strongly
      coupled finite clusters: An adaptive mutation-driven strategy.
AB  - We propose and implement a simple adaptive heuristic to optimize the geometries
      of clusters of point charges or ions with the ability to find the global minimum
      energy configurations. The approach uses random mutations of a single string
      encoding the geometry and accepts moves that decrease the energy. Mutation
      probability and mutation intensity are allowed to evolve adaptively on the basis
      of continuous evaluation of past explorations. The resulting algorithm has been
      called Completely Adaptive Random Mutation Hill Climbing method. We have
      implemented this method to search through the complex potential energy landscapes
      of parabolically confined 3D classical Coulomb clusters of hundreds or thousands
      of charges--usually found in high frequency discharge plasmas. The energy per
      particle (EN/N) and its first and second differences, structural features,
      distribution of the oscillation frequencies of normal modes, etc., are analyzed
      as functions of confinement strength and the number of charges in the system.
      Certain magic numbers are identified. In order to test the feasibility of the
      algorithm in cluster geometry optimization on more complex energy landscapes, we
      have applied the algorithm for optimizing the geometries of MgO clusters,
      described by Coulomb-Born-Mayer potential and finding global minimum of some
      Lennard-Jones clusters. The convergence behavior of the algorithm compares
      favorably with those of other existing global optimizers.

PMID- 23968072
TI  - Wave function methods for fractional electrons.
AB  - Determining accurate chemical potentials is of considerable interest in various
      chemical and physical contexts: from small molecular charge-transfer complexes to
      bandgap in bulk materials such as semi-conductors. Chemical potentials are
      typically evaluated either by density functional theory, or, alternatively, by
      computationally more intensive Greens function based GW computations. To
      calculate chemical potentials, the ground state energy needs to be defined for
      fractional charges. We thus explore an extension of wave function theories to
      fractional charges, and investigate the ionization potential and electron
      affinity as the derivatives of the energy with respect to the electron number.
      The ultimate aim is to access the chemical potential of correlated wave function
      methods without the need of explicitly changing the numbers of electrons, making
      the approach readily applicable to bulk materials. We find that even though
      second order perturbation theory reduces the fractional charge error considerably
      compared to Hartree-Fock and standard density functionals, higher order
      perturbation theory is more accurate and coupled-cluster approaches are even more
      robust, provided the electrons are bound at the Hartree-Fock level. The success
      of post-HF approaches to improve over HF relies on two equally important aspects:
      the integer values are more accurate and the Coulomb correlation between the
      fractionally occupied orbital and all others improves the straight line behavior
      significantly as identified by a correction to Hartree-Fock. Our description of
      fractional electrons is also applicable to fractional spins, illustrating the
      ability of coupled-cluster singles and doubles to deal with two degenerate
      fractionally occupied orbitals, but its inadequacy for three and more fractional
      spins, which occur, for instance, for spherical atoms and when dissociating
      double bonds. Our approach explores the realm of typical wave function methods
      that are applied mostly in molecular chemistry, but become available to the solid
      state community and offer the advantage of an integrated approach: fundamental
      gap, relative energies, and optimal geometries can be obtained at the same level.

PMID- 23968073
TI  - A Lagrange multiplier approach for excited state properties through intermediate
      Hamiltonian formulation of Fock space multireference coupled-cluster theory.
AB  - In this paper, we present a formulation based on Lagrange multiplier approach for
      efficient evaluation of excited state energy derivatives in Fock space coupled
      cluster theory within the intermediate Hamiltonian framework. The formulation is
      applied to derive the explicit generic expressions up to second order energy
      derivatives for [1, 1] sector of Fock space with singles and doubles
      approximation. Its advantage, efficiency, and interconnection in comparison to
      the Lagrange multiplier approach in traditional formulation of Fock space, which
      is built on the concept of Bloch equation based effective Hamiltonian, has been
      discussed. Computational strategy for their implementation has also been
      discussed in some detail. 

PMID- 23968074
TI  - A quasi-continuum hydrodynamic model for slit shaped nanochannel flow.
AB  - We propose a quasi-continuum hydrodynamic model for isothermal transport of
      Lennard-Jones fluid confined in slit shaped nanochannels. In this work, we
      compute slip and viscous contributions independently and superimpose them to
      obtain the total velocity profile. Layering of fluid near the interface plays an
      important role in viscous contribution to the flow, by apparent viscosity change
      along the confining dimension. This relationship necessitates computing density
      profiles, which is done using the recently proposed empirical-potential based
      quasi-continuum theory [A. V. Raghunathan, J. H. Park, and N. R. Aluru, J. Chem.
      Phys. 127, 174701 (2007)]. Existing correlations for density dependent viscosity
      provided by Woodcock [AIChE J. 52, 438 (2006)] are used to compute viscosity
      profile in the nanopores. A Dirichlet type slip boundary condition based on a
      static Langevin friction model describing center-of-mass motion of fluid
      particles is used, the parameters of which are dependent on the fluctuations of
      total wall-fluid force from an equilibrium molecular dynamics simulation.
      Different types of corrugated surfaces are considered to study wall-fluid
      friction effects on boundary conditions. Proposed hydrodynamic model yields good
      agreement of velocity profiles obtained from non-equilibrium molecular dynamics
      simulations for gravity driven flow. 

PMID- 23968075
TI  - A density functional for strong correlation in atoms.
AB  - In this work, a strong-correlation model is developed for use with the Becke
      Roussel exchange and dynamical correlation functionals. The model is free of
      empirical parameters and is exact for the hydrogen atom. It significantly
      improves on results from conventional functionals for the relative energies of
      spin-polarized and spin-averaged atoms through the first three rows of the
      periodic table, giving a mean absolute error of only 4 kcal/mol. The dissociation
      curve for the H2 molecule is also considered. 

PMID- 23968076
TI  - Nuclear dynamics of decaying states: A semiclassical approach.
AB  - A semiclassical method is proposed for carrying out molecular fragmentation
      simulations following electronic decay processes. The nuclear motion is treated
      classically during and after the electronic decay while a quantum mechanical
      description is used for the electron dynamics. The method is compared with full
      quantum results for benchmark examples. Good agreement is achieved. Such a method
      should be very useful for studying large systems for which a quantum description
      is not feasible. 

PMID- 23968077
TI  - Efficient construction of exchange and correlation potentials by inverting the
      Kohn-Sham equations.
AB  - Given a set of canonical Kohn-Sham orbitals, orbital energies, and an external
      potential for a many-electron system, one can invert the Kohn-Sham equations in a
      single step to obtain the corresponding exchange-correlation potential, vXC(r).
      For orbitals and orbital energies that are solutions of the Kohn-Sham equations
      with a multiplicative vXC(r) this procedure recovers vXC(r) (in the basis set
      limit), but for eigenfunctions of a non-multiplicative one-electron operator it
      produces an orbital-averaged potential. In particular, substitution of Hartree
      Fock orbitals and eigenvalues into the Kohn-Sham inversion formula is a fast way
      to compute the Slater potential. In the same way, we efficiently construct
      orbital-averaged exchange and correlation potentials for hybrid and kinetic
      energy-density-dependent functionals. We also show how the Kohn-Sham inversion
      approach can be used to compute functional derivatives of explicit density
      functionals and to approximate functional derivatives of orbital-dependent
      functionals. 

PMID- 23968078
TI  - Lossless compression of wave function information using matrix factorization: A
      "gzip" for quantum chemistry.
AB  - We propose the use of the singular value decomposition to decrease the storage
      required for wave function information. The specific case considered is
      determinantal full configuration interaction, but the same technique is readily
      applicable to truncated configuration interaction and coupled-cluster
      calculations of various types; as we discuss this is a reformulation of
      approximate methods that have been in use for some time, but our approach
      eliminates those approximations. Numerical examples support the contention that
      considerable compression of the wave function is possible without significant
      loss of accuracy: as expected a considerable amount of the information contained
      in the full CI wave function is redundant. 

PMID- 23968079
TI  - Extending molecular simulation time scales: Parallel in time integrations for
      high-level quantum chemistry and complex force representations.
AB  - Parallel in time simulation algorithms are presented and applied to conventional
      molecular dynamics (MD) and ab initio molecular dynamics (AIMD) models of
      realistic complexity. Assuming that a forward time integrator, f (e.g., Verlet
      algorithm), is available to propagate the system from time ti (trajectory
      positions and velocities xi = (ri, vi)) to time ti + 1 (xi + 1) by xi + 1 =
      fi(xi), the dynamics problem spanning an interval from t0[ellipsis
      (horizontal)]tM can be transformed into a root finding problem, F(X) = [xi -
      f(x(i - 1)]i = 1, M = 0, for the trajectory variables. The root finding problem
      is solved using a variety of root finding techniques, including quasi-Newton and
      preconditioned quasi-Newton schemes that are all unconditionally convergent. The
      algorithms are parallelized by assigning a processor to each time-step entry in
      the columns of F(X). The relation of this approach to other recently proposed
      parallel in time methods is discussed, and the effectiveness of various
      approaches to solving the root finding problem is tested. We demonstrate that
      more efficient dynamical models based on simplified interactions or coarsening
      time-steps provide preconditioners for the root finding problem. However, for MD
      and AIMD simulations, such preconditioners are not required to obtain reasonable
      convergence and their cost must be considered in the performance of the
      algorithm. The parallel in time algorithms developed are tested by applying them
      to MD and AIMD simulations of size and complexity similar to those encountered in
      present day applications. These include a 1000 Si atom MD simulation using
      Stillinger-Weber potentials, and a HCl + 4H2O AIMD simulation at the MP2 level.
      The maximum speedup (serial execution/timeparallel execution time) obtained by
      parallelizing the Stillinger-Weber MD simulation was nearly 3.0. For the AIMD MP2
      simulations, the algorithms achieved speedups of up to 14.3. The parallel in time
      algorithms can be implemented in a distributed computing environment using very
      slow transmission control protocol/Internet protocol networks. Scripts written in
      Python that make calls to a precompiled quantum chemistry package (NWChem) are
      demonstrated to provide an actual speedup of 8.2 for a 2.5 ps AIMD simulation of
      HCl + 4H2O at the MP2/6-31G* level. Implemented in this way these algorithms can
      be used for long time high-level AIMD simulations at a modest cost using machines
      connected by very slow networks such as WiFi, or in different time zones
      connected by the Internet. The algorithms can also be used with programs that are
      already parallel. Using these algorithms, we are able to reduce the cost of a
      MP2/6-311++G(2d,2p) simulation that had reached its maximum possible speedup in
      the parallelization of the electronic structure calculation from 32 s/time step
      to 6.9 s/time step.

PMID- 23968080
TI  - Information-theoretic tools for parametrized coarse-graining of non-equilibrium
      extended systems.
AB  - In this paper, we focus on the development of new methods suitable for efficient
      and reliable coarse-graining of non-equilibrium molecular systems. In this
      context, we propose error estimation and controlled-fidelity model reduction
      methods based on Path-Space Information Theory, combined with statistical
      parametric estimation of rates for non-equilibrium stationary processes. The
      approach we propose extends the applicability of existing information-based
      methods for deriving parametrized coarse-grained models to Non-Equilibrium
      systems with Stationary States. In the context of coarse-graining it allows for
      constructing optimal parametrized Markovian coarse-grained dynamics within a
      parametric family, by minimizing information loss (due to coarse-graining) on the
      path space. Furthermore, we propose an asymptotically equivalent method-related
      to maximum likelihood estimators for stochastic processes-where the coarse
      graining is obtained by optimizing the information content in path space of the
      coarse variables, with respect to the projected computational data from a fine
      scale simulation. Finally, the associated path-space Fisher Information Matrix
      can provide confidence intervals for the corresponding parameter estimators. We
      demonstrate the proposed coarse-graining method in (a) non-equilibrium systems
      with diffusing interacting particles, driven by out-of-equilibrium boundary
      conditions, as well as (b) multi-scale diffusions and the corresponding
      stochastic averaging limits, comparing them to our proposed methodologies. 

PMID- 23968081
TI  - Generation of strong electric fields in an ice film capacitor.
AB  - We present a capacitor-type device that can generate strong electrostatic field
      in condensed phase. The device comprises an ice film grown on a cold metal
      substrate in vacuum, and the film is charged by trapping Cs(+) ions on the ice
      surface with thermodynamic surface energy. Electric field within the charged film
      was monitored through measuring the film voltage using a Kelvin work function
      probe and the vibrational Stark effect of acetonitrile using IR spectroscopy.
      These measurements show that the electric field can be increased to ~4 * 10(8) V
      m(-1), higher than that achievable by conventional metal plate capacitors. In
      addition, the present device may provide several advantages in studying the
      effects of electric field on molecules in condensed phase, such as the ability to
      control the sample composition and structure at molecular scale and the
      spectroscopic monitoring of the sample under electric field. 

PMID- 23968082
TI  - Highlighting short-lived excited electronic states with pump-degenerate-four-wave
      mixing.
AB  - Detection of short-lived transient species is a major challenge in femtosecond
      spectroscopy, especially when third-order techniques like transient absorption
      are used. Higher order methods employ additional interactions between light and
      matter to highlight such transient species. In this work we address numerically
      and experimentally the detection of ultrafast species with pump-Degenerate Four
      Wave Mixing (pump-DFWM). In this respect, conclusive identification of ultrafast
      species requires the proper determination of time-zero between all four laser
      pulses (pump pulse and the DFWM sequence). This is addressed here under the light
      of experimental parameters as well as molecular properties: The role of pulse
      durations, amount of pulse chirp as well as excited state life time is
      investigated by measuring a row of natural pigments differing mainly in the
      number of conjugated double bonds (N = 9 to 13). A comparison of the different
      signals reveals a strikingly unusual behavior of spheroidene (N = 10). Complete
      analysis of the pump-DFWM signal illustrates the power of the method and clearly
      assigns the uniqueness of spheroidene to a mixing of the initially excited state
      with a dark excited electronic state. 

PMID- 23968083
TI  - Measurement of Soret and Fickian diffusion coefficients by orthogonal phase
      shifting interferometry and its application to protein aqueous solutions.
AB  - We have developed a method to measure thermodiffusion and Fickian diffusion in
      transparent binary solutions. The measuring instrument consists of two
      orthogonally aligned phase-shifting interferometers coupled with a single
      rotating polarizer. This high-resolution interferometer, initially developed to
      measure isothermal diffusion coefficients in liquid systems [J. F. Torres, A.
      Komiya, E. Shoji, J. Okajima, and S. Maruyama, Opt. Lasers Eng. 50, 1287 (2012)],
      was modified to measure transient concentration profiles in binary solutions
      subject to a linear temperature gradient. A convectionless thermodiffusion field
      was created in a binary solution sample that is placed inside a Soret cell. This
      cell consists of a parallelepiped cavity with a horizontal cross-section area of
      10 * 20 mm(2), a variable height of 1-2 mm, and transparent lateral walls. The
      small height of the cell reduces the volume of the sample, shortens the
      measurement time, and increases the hydrodynamic stability of the system. An
      additional free diffusion experiment with the same optical apparatus provides the
      so-called contrast factors that relate the unwrapped phase and concentration
      gradients, i.e., the measurement technique is independent and robust. The Soret
      coefficient is determined from the concentration and temperature differences
      between the upper and lower boundaries measured by the interferometer and
      thermocouples, respectively. The Fickian diffusion coefficient is obtained by
      fitting a numerical solution to the experimental concentration profile. The
      method is validated through the measurement of thermodiffusion in the well-known
      liquid pairs of ethanol-water (ethanol 39.12 wt.%) and isobutylbenzene-dodecane
      (50.0 wt.%). The obtained coefficients agree with the literature values within
      5.0%. Finally, the developed technique is applied to visualize biomolecular
      thermophoresis. Two protein aqueous solutions at 3 mg/ml were used as samples:
      aprotinin (6.5 kDa)-water and lysozyme (14.3 kDa)-water. It was found that the
      former protein molecules are thermophilic and the latter thermophobic. In
      contrast to previously reported methods, this technique is suitable for both
      short time and negative Soret coefficient measurements. 

PMID- 23968084
TI  - Optical preparation of H2 rovibrational levels with almost complete population
      transfer.
AB  - Using stimulated Raman adiabatic passage (SARP), it is possible, in principle, to
      transfer all the population in a rovibrational level of an isolated diatomic
      molecule to an excited rovibrational level. We use an overlapping sequence of
      pump (532 nm) and dump (683 nm) single-mode laser pulses of unequal fluence to
      prepare isolated H2 molecules in a molecular beam. In a first series of
      experiments we were able to transfer more than half the population to an excited
      rovibrational level [N. Mukherjee, W. R. Dong, J. A. Harrison, and R. N. Zare, J.
      Chem. Phys. 138(5), 051101-1-051101-4 (2013)]. Since then, we have achieved
      almost complete transfer (97% +/- 7%) of population from the H2 (v = 0, J = 0)
      ground rovibrational level to the H2 (v = 1, J = 0) excited rovibrational level.
      An explanation is presented of the SARP process and how these results are
      obtained. 

PMID- 23968085
TI  - Measurement of the true transverse nuclear magnetic resonance relaxation in the
      presence of field gradients.
AB  - A measure of the nuclear spin transverse relaxation time T2, as determined using
      the nuclear magnetic resonance Carr-Purcell Meiboom-Gill (CPMG) experiment,
      provides unique information characterizing the microstructure of porous media
      which are themselves ubiquitous across fields of petrophysics, biophysics, and
      chemical engineering. However, the CPMG measurement is sensitive to diffusion in
      large magnetic field gradients. Under such conditions an effective relaxation
      time T2,eff is observed instead, described by a combination of relaxation and
      diffusion exponents. The relaxation exponent always varies as nte (where n is the
      number, and te is the temporal separation, of spin echoes). The diffusion
      exponent varies as nte (k), where 1 < k <= 3, although the exact analytic form is
      often unknown. Here we present a general approach to separating the influence of
      relaxation and diffusion by utilizing a composite diffusion exponent. Any T2,eff
      component with a power of k > 1 is removed to provide a measure of the true T2
      relaxation time distribution from CPMG data acquired in the presence of a strong
      background gradient. We apply the technique to discriminate between the effects
      of relaxation and diffusion in porous media using catalysts and rocks as
      examples. The method is generally applicable to any CPMG measurements conducted
      in the presence of a static magnetic field gradient. 

PMID- 23968086
TI  - Collisional excitation of CN(X2Sigma+) by para- and ortho-H2: Fine-structure
      resolved transitions.
AB  - We present a new four dimensional potential energy surface (PES) for the
      CN(X(2)Sigma(+))-H2 system. Both molecules were treated as rigid rotors.
      Potential energy was obtained from the electronic structure calculations using a
      partially spin-restricted coupled cluster with single, double, and perturbative
      triple excitations method. The four atoms were described using the augmented
      correlation-consistent triple zeta (aug-cc-pVTZ) basis sets augmented with mid
      bond functions for improved description of van der Waals interactions. The global
      minimum is characterized by the well depth of 121.36 cm(-1) for the linear
      CN???H2 structure. The zero-order corrected dissociation energies D0 are 27.73
      cm(-1) and 38.75 cm(-1) for the complex with para- and ortho-H2, respectively.
      These theoretical results obtained using our new PES are in excellent agreement
      with experimental values [Y. Chen and M. C. Heaven, J. Chem. Phys. 109, 5171
      (1998)]. We perform fully quantum close coupling calculations of the rotationally
      inelastic cross sections of CN in collisions with para-H2 and ortho-H2 at low and
      intermediate energies. Corresponding rate coefficients were compared with
      experimental results of Brunet et al. [J. Chem. Phys. 116, 3617 (2002)]. A good
      agreement between theoretical and experimental results was found. Fine-structure
      resolved cross sections were then obtained through a recoupling technique.
      Significant differences exist between para- and ortho-H2 results. The propensity
      rules between fine-structure levels are also studied, and it is shown that the
      cross sections for Deltaj = DeltaN transitions are much larger than those for
      Deltaj ? DeltaN transitions, as expected from theoretical considerations. 

PMID- 23968087
TI  - Kinetic and dynamic studies of the Cl(2Pu) + H2O(X1A1) -> HCl(X1Sigma+) +
      OH(X2Pi) reaction on an ab initio based full-dimensional global potential energy
      surface of the ground electronic state of ClH2O.
AB  - Extensive high-level ab initio calculations were performed on the ground
      electronic state of ClH2O. The barrier region for the title reaction was found to
      have significant multi-reference character, thus favoring the multi-reference
      configuration interaction (MRCI) method over single-reference methods such as
      coupled-cluster. A full-dimensional global potential energy surface was developed
      by fitting about 25 000 MRCI points using the permutation invariant polynomial
      method. The reaction path features a "late" barrier flanked by deep pre- and post
      barrier wells. Calculated rate constants for the forward reaction are in
      reasonable agreement with experiment, suggesting a good representation of the
      forward barrier. The dynamics of the forward reaction was also investigated using
      a quasi-classical trajectory method at energies just above the barrier. While the
      OH bond is found to be a spectator, the HCl product has significant rotational
      excitation. The reaction proceeds via both direct rebound and stripping
      mechanisms, leading to backward and sideways scattering. 

PMID- 23968088
TI  - Theoretical study of the electronic excitations of free-base porphyrin-Ar2 van
      der Waals complexes.
AB  - The intermolecular interaction of free-base porphine (FBP)-Ar2 and free-base
      tetraazaporphyrin (FBPz)-Ar2 van der Waals (vdW) complexes was calculated in the
      ground state and vertical excitations that correspond to the Q- and B-bands using
      the many-body wavefunction theory of the symmetry-adapted cluster-configuration
      interaction (SAC-CI) method and time-dependent density functional theory (TDDFT).
      For the 1(1)B3u state of FBP-Ar2 a blueshift (high-energy shift) of excitation
      energy was calculated using the SAC-CI method; such a blueshift was not obtained
      by TDDFT calculations. This calculated blueshift corresponds to the
      experimentally observed blueshift in the Qx-band of FBP for FBP-Arn complexes.
      For FBPz-Ar2, blueshifts of the Q-band were not obtained using SAC-CI and TDDFT.
      These behaviors of the energy shift of the Q-bands could not be explained by the
      point dipole-point dipole interaction model. Large redshifts (low-energy shift)
      were obtained for the B-band states (2(1)B3u and 2(1)B2u) of FBP and FBPz. The
      energy shift showed the inverse sixth-power dependence on the intermolecular
      distance. The point dipole-point dipole interaction model can describe the
      redshift of the B-band. For the excited states that exhibit large redshifts, the
      TDDFT can qualitatively describe the vdW interaction in the excited states by
      supermolecular calculations. The solvatochromic shifts for FBP and FBPz in an Ar
      matrix were examined by the linear-response polarizable continuum model and
      TDDFT. The magnitude of calculated solvatochromic redshifts is proportional to
      the square of the transition dipole moment. 

PMID- 23968089
TI  - Infrared intensities and charge mobility in hydrogen bonded complexes.
AB  - The analytical model for the study of charge mobility in the molecules presented
      by Galimberti et al. [J. Chem. Phys. 138, 164115 (2013)] is applied to hydrogen
      bonded planar dimers. Atomic charges and charge fluxes are obtained from density
      functional theory computed atomic polar tensors and related first derivatives,
      thus providing an interpretation of the IR intensity enhancement of the X-H
      stretching band observed upon aggregation. Our results show that both principal
      and non-principal charge fluxes have an important role for the rationalization of
      the spectral behavior; moreover, they demonstrate that the modulation of the
      charge distribution during vibrational motions of the -XH?Y- fragment is not
      localized exclusively on the atoms directly involved in hydrogen bonding. With
      these premises we made some correlations between IR intensities, interaction
      energies, and charge fluxes. The model was tested on small dimers and
      subsequently to the bigger one cytosine-guanine. Thus, the model can be applied
      to complex systems. 

PMID- 23968090
TI  - An ab initio study of the ground and low-lying excited states of KBe with the
      effect of inner-shell electrons.
AB  - The potential energy curves (PECs) of 1(2)Sigma(+), 2(2)Sigma(+), 1(2)Pi, and
      2(2)Pi states of KBe are calculated using multireference configuration
      interaction method and large all-electron basis sets. Four sets of frozen core
      orbitals (FCOs) are considered to examine the effect of inner-shell correlation
      electrons on the molecular properties. The ro-vibrational energy levels are
      obtained by solving the Schrodinger equation of nuclear motion based on the ab
      initio PECs. The spectroscopic parameters are determined from the ro-vibrational
      levels with Dunham expansion. The PECs are fitted into analytical potential
      energy functions using the Morse long-range potential function. The dipole moment
      functions of the states for KBe calculated with different FCOs are presented. The
      transition dipole moments for KBe between 1(2)Sigma(+) and 2(2)Sigma(+) states,
      1(2)Pi and 1(2)Sigma(+) states, and 2(2)Pi and 1(2)Sigma(+) states are also
      obtained. 

PMID- 23968091
TI  - Ro-vibrational quenching of CO (v = 1) by He impact in a broad range of
      temperatures: A benchmark study using mixed quantum/classical inelastic
      scattering theory.
AB  - The mixed quantum/classical approach is applied to the problem of ro-vibrational
      energy transfer in the inelastic collisions of CO(v = 1) with He atom, in order
      to predict the quenching rate coefficient in a broad range of temperatures 5 < T
      < 2500 K. Scattering calculations are done in two different ways: direct
      calculations of quenching cross sections and, alternatively, calculations of the
      excitation cross sections plus microscopic reversibility. In addition, a
      symmetrized average-velocity method of Billing is tried. Combination of these
      methods allows reproducing experiment in a broad range of temperatures. Excellent
      agreement with experiment is obtained at 400 < T < 2500 K (within 10%), good
      agreement in the range 100 < T < 400 K (within 25%), and semi-quantitative
      agreement at 40 < T < 100 K(within a factor of 2). This study provides a
      stringent test of the mixed quantum/classical theory, because the vibrational
      quantum in CO molecule is rather large and the quencher is very light (He atom).
      For heavier quenchers and closer to dissociation limit of the molecule, the mixed
      quantum/classical theory is expected to work even better.

PMID- 23968092
TI  - Electronic states of porphycene-O2 complex and photoinduced singlet O2
      production.
AB  - Porphycene (PC), a structural isomer of porphine, is a promising photosensitizer
      for photodynamic therapy. Its excited states can be quenched by molecular oxygen,
      generating singlet O2. The electronic structures of PC and of the PC?O2 complex
      were investigated using complete active space perturbation theory. It is shown
      that singlet oxygen generation involves 12 electronic states of the complex, with
      singlet, triplet, and quintet multiplicities. Two scenarios for singlet-O2 yield
      are analyzed: (I) quenching of triplet states of PC and (II) quenching of singlet
      states of PC. In the first scenario, which is favored under low O2 concentration,
      singlet-O2 yield is limited by the relatively low triplet quantum yield of PC. We
      discuss how the singlet-O2 yield would be busted if conditions for occurrence of
      the second scenario could be achieved. 

PMID- 23968093
TI  - Electron dynamics of molecular double ionization by circularly polarized laser
      pulses.
AB  - Using the classical ensemble method, we have investigated double ionization (DI)
      of diatomic molecules driven by circularly polarized laser pulses with different
      internuclear distances (R). The results show that the DI mechanism changes from
      sequential double ionization (SDI) to nonsequential double ionization (NSDI) as
      the internuclear distance increases. In SDI range, the structure of the electron
      momentum distribution changes seriously as R increases, which indicates the
      sensitive dependence of the release times of the two electrons on R. For NSDI,
      because of the circular polarization, the ionization of the second electron is
      not through the well-known recollision process but through a process where the
      first electron ionizes over the inner potential barrier of the molecule, moves
      directly towards the other nucleus, and kicks out the second electron. 

PMID- 23968094
TI  - Large scale molecular dynamics simulations of homogeneous nucleation.
AB  - We present results from large-scale molecular dynamics (MD) simulations of
      homogeneous vapor-to-liquid nucleation. The simulations contain between 1 * 10(9)
      and 8 * 10(9) Lennard-Jones (LJ) atoms, covering up to 1.2 MUs (56 * 10(6) time
      steps). They cover a wide range of supersaturation ratios, S ? 1.55-10(4), and
      temperatures from kT = 0.3 to 1.0epsilon (where epsilon is the depth of the LJ
      potential, and k is the Boltzmann constant). We have resolved nucleation rates as
      low as 10(17) cm(-3) s(-1) (in the argon system), and critical cluster sizes as
      large as 100 atoms. Recent argon nucleation experiments probe nucleation rates in
      an overlapping range, making the first direct comparison between laboratory
      experiments and molecular dynamics simulations possible: We find very good
      agreement within the uncertainties, which are mainly due to the extrapolations of
      argon and LJ saturation curves to very low temperatures. The self-consistent,
      modified classical nucleation model of Girshick and Chiu [J. Chem. Phys. 93, 1273
      (1990)] underestimates the nucleation rates by up to 9 orders of magnitudes at
      low temperatures, and at kT = 1.0epsilon it overestimates them by up to 10(5).
      The predictions from a semi-phenomenological model by Laaksonen et al. [Phys.
      Rev. E 49, 5517 (1994)] are much closer to our MD results, but still differ by
      factors of up to 10(4) in some cases. At low temperatures, the classical theory
      predicts critical clusters sizes, which match the simulation results (using the
      first nucleation theorem) quite well, while the semi-phenomenological model
      slightly underestimates them. At kT = 1.0epsilon, the critical sizes from both
      models are clearly too small. In our simulations the growth rates per encounter,
      which are often taken to be unity in nucleation models, lie in a range from 0.05
      to 0.24. We devise a new, empirical nucleation model based on free energy
      functions derived from subcritical cluster abundances, and find that it performs
      well in estimating nucleation rates. 

PMID- 23968095
TI  - Anharmonic theoretical simulations of infrared spectra of halogenated organic
      compounds.
AB  - The recent implementation of the computation of infrared (IR) intensities beyond
      the double-harmonic approximation [J. Bloino and V. Barone, J. Chem. Phys. 136,
      124108 (2012)] paved the route to routine calculations of infrared spectra for a
      wide set of molecular systems. Halogenated organic compounds represent an
      interesting class of molecules, from both an atmospheric and computational point
      of view, due to the peculiar chemical features related to the halogen atoms. In
      this work, we simulate the IR spectra of eight halogenated molecules (CH2F2,
      CHBrF2, CH2DBr, CF3Br, CH2CHF, CF2CFCl, cis-CHFCHBr, cis-CHFCHI), using two
      common hybrid and double-hybrid density functionals in conjunction with both
      double- and triple-zeta quality basis sets (SNSD and cc-pVTZ) as well as
      employing the coupled-cluster theory with basis sets of at least triple-zeta
      quality. Finally, we compare our results with available experimental spectra,
      with the aim of checking the accuracy and the performances of the computational
      approaches. 

PMID- 23968096
TI  - In situ Brillouin study of sodium alumino silicate glasses under pressure.
AB  - The in situ elastic and plastic behaviors of sodium aluminosilicate glasses with
      different degrees of depolymerization were analyzed using Brillouin spectroscopy.
      The observed elastic anomaly progressively vanished with depolymerization. The
      densification process appears to be different from that observed in pure silica
      glass. In the plastic regime of densified glasses hysteresis loops were observed
      and related to modification of the local silicon environment facilitated by the
      addition of sodium. 

PMID- 23968097
TI  - Local and bulk melting of shocked columnar nanocrystalline Cu: Dynamics,
      anisotropy, premelting, superheating, supercooling, and re-crystallization.
AB  - We perform large-scale molecular dynamics simulations to study shock-induced
      melting transition of idealized hexagonal columnar nanocrystalline Cu. The as
      constructed nanocrystalline Cu consists of unrotated (reference) and rotated
      columnar crystals, relative to the columnar axis. Shock loading is applied along
      three principal directions of the columnar Cu: two transverse (zigzag and
      armchair) and one longitudinal directions. Dynamic local melting processes are
      highly anisotropic with respect to the shock directions. For the transverse
      directions, hotspot effect and disparate dynamic responses of grains with
      different orientations may lead to partial or complete premelting of the
      initially rotated grains, which in turn leads to transient supercooling and
      heterogeneous recrystallization, and thus, the formation of nanocrystalline
      solids with modified grain structures or solid-liquid mixtures, depending on the
      extent of supercooling. With increasing shock strengths, the reference grains
      melt heterogeneously at interfaces and homogeneously inside. Conversely, "bulk"
      premelting of the rotated grains is absent for the longitudinal direction, except
      for grain boundary melting. The progression of recrystallization or heterogenous
      melting diminishes and eventually eliminates the transient premelting or
      superheating of the system via latent heat and thermal diffusion. Premelting or
      superheating appears unlikely for bulk melting or well-defined Hugoniot states,
      if the thermal and mechanical equilibria are achieved, and the thermodynamic
      melting curve coincides with the partial melting Hugoniot states of a
      polycrystalline solid. 

PMID- 23968098
TI  - Theoretical determination of anisotropic thermal conductivity for crystalline
      1,3,5-triamino-2,4,6-trinitrobenzene (TATB).
AB  - Bond stretching and three-center angle bending potentials have been developed to
      extend an existing rigid-bond 1,3,5-triamino-2,4,6-trinitrobenzene molecular
      dynamics force field [D. Bedrov, O. Borodin, G. D. Smith, T. D. Sewell, D. M.
      Dattelbaum, and L. L. Stevens, J. Chem. Phys. 131, 224703 (2009)] for simulations
      requiring fully flexible molecules. The potentials were fit to experimental
      vibrational spectra and electronic structure predictions of vibrational normal
      modes using a combination of zero kelvin eigenmode analysis for the isolated
      molecule and power spectra for the isolated molecule and crystal. A reverse non
      equilibrium molecular dynamics method [F. Muller-Plathe, J. Chem. Phys. 106, 6082
      (1997)] was used to obtain the room temperature, atmospheric pressure thermal
      conductivity along three directions in a well-defined, non-orthogonal basis. The
      thermal conductivity was found to be significantly anisotropic with values 1.13
      +/- 0.07, 1.07 +/- 0.07, and 0.65 +/- 0.03 W m(-1) K(-1) for directions nominally
      parallel to the a, b, and c lattice vectors, respectively. 

PMID- 23968099
TI  - The quantum nature of the OH stretching mode in ice and water probed by neutron
      scattering experiments.
AB  - The OH stretching vibrational spectrum of water was measured in a wide range of
      temperatures across the triple point, 269 K <T < 296 K, using Inelastic Neutron
      Scattering (INS). The hydrogen projected density of states and the proton mean
      kinetic energy, <EK>OH, were determined for the first time within the framework
      of a harmonic description of the proton dynamics. We found that in the liquid the
      value of <EK>OH is nearly constant as a function of T, indicating that quantum
      effects on the OH stretching frequency are weakly dependent on temperature. In
      the case of ice, ab initio electronic structure calculations, using non-local van
      der Waals functionals, provided <EK>OH values in agreement with INS experiments.
      We also found that the ratio of the stretching (<EK>OH) to the total (<EK>exp)
      kinetic energy, obtained from the present measurements, increases in going from
      ice, where hydrogen bonding is the strongest, to the liquid at ambient conditions
      and then to the vapour phase, where hydrogen bonding is the weakest. The same
      ratio was also derived from the combination of previous deep inelastic neutron
      scattering data, which does not rely upon the harmonic approximation, and the
      present measurements. We found that the ratio of stretching to the total kinetic
      energy shows a minimum in the metastable liquid phase. This finding suggests that
      the strength of intermolecular interactions increases in the supercooled phase,
      with respect to that in ice, contrary to the accepted view that supercooled water
      exhibits weaker hydrogen bonding than ice.

PMID- 23968100
TI  - Structural properties of fluids interacting via piece-wise constant potentials
      with a hard core.
AB  - The structural properties of fluids whose molecules interact via potentials with
      a hard core plus two piece-wise constant sections of different widths and heights
      are presented. These follow from the more general development previously
      introduced for potentials with a hard core plus n piece-wise constant sections
      [A. Santos, S. B. Yuste, and M. Lopez de Haro, Condens. Matter Phys. 15, 23602
      (2012)] in which use was made of a semi-analytic rational-function approximation
      method. The results of illustrative cases comprising eight different combinations
      of wells and shoulders are compared both with simulation data and with those that
      follow from the numerical solution of the Percus-Yevick and hypernetted-chain
      integral equations. It is found that the rational-function approximation
      generally predicts a more accurate radial distribution function than the Percus
      Yevick theory and is comparable or even superior to the hypernetted-chain theory.
      This superiority over both integral equation theories is lost, however, at high
      densities, especially as the widths of the wells and/or the barriers increase. 

PMID- 23968101
TI  - Linking molecular level chemistry to macroscopic combustion behavior for nano
      energetic materials with halogen containing oxides.
AB  - Coupling molecular scale reaction kinetics with macroscopic combustion behavior
      is critical to understanding the influences of intermediate chemistry on energy
      propagation, yet bridging this multi-scale gap is challenging. This study
      integrates ab initio quantum chemical calculations and condensed phase density
      functional theory to elucidate factors contributing to experimentally measured
      high flame speeds (i.e., >900 m/s) associated with halogen based energetic
      composites, such as aluminum (Al) and iodine pentoxide (I2O5). Experiments show a
      direct correlation between apparent activation energy and flame speed suggesting
      that flame speed is directly influenced by chemical kinetics. Toward this end,
      the first principle simulations resolve key exothermic surface and intermediate
      chemistries contributing toward the kinetics that promote high flame speeds.
      Linking molecular level exothermicity to macroscopic experimental investigations
      provides insight into the unique role of the alumina oxide shell passivating
      aluminum particles. In the case of Al reacting with I2O5, the alumina shell
      promotes exothermic surface chemistries that reduce activation energy and
      increase flame speed. This finding is in contrast to Al reaction with metal
      oxides that show the alumina shell does not participate exothermically in the
      reaction. 

PMID- 23968102
TI  - Chemistry at molecular junctions: Rotation and dissociation of O2 on the Ag(110)
      surface induced by a scanning tunneling microscope.
AB  - The scanning tunneling microscope (STM) is a fascinating tool used to perform
      chemical processes at the single-molecule level, including bond formation, bond
      breaking, and even chemical reactions. Hahn and Ho [J. Chem. Phys. 123, 214702
      (2005)] performed controlled rotations and dissociations of single O2 molecules
      chemisorbed on the Ag(110) surface at precise bias voltages using STM. These
      threshold voltages were dependent on the direction of the bias voltage and the
      initial orientation of the chemisorbed molecule. They also observed an
      interesting voltage-direction-dependent and orientation-dependent pathway
      selectivity suggestive of mode-selective chemistry at molecular junctions, such
      that in one case the molecule underwent direct dissociation, whereas in the other
      case it underwent rotation-mediated dissociation. We present a detailed, first
      principles-based theoretical study to investigate the mechanism of the tunneling
      induced O2 dynamics, including the origin of the observed threshold voltages, the
      pathway dependence, and the rate of O2 dissociation. Results show a direct
      correspondence between the observed threshold voltage for a process and the
      activation energy for that process. The pathway selectivity arises from a
      competition between the voltage-modified barrier heights for rotation and
      dissociation, and the coupling strength of the tunneling electrons to the
      rotational and vibrational modes of the adsorbed molecule. Finally, we explore
      the "dipole" and "resonance" mechanisms of inelastic electron tunneling to
      elucidate the energy transfer between the tunneling electrons and chemisorbed O2.

PMID- 23968103
TI  - Effect of contact area on electron transport through graphene-metal interface.
AB  - We perform first-principles investigations of electron transport in armchair
      graphene nanoribbons adsorbed on Cu(111) and Ni(111) surfaces with various
      contact areas. We find that the contact area between metals and graphene has
      different influences on the conductance. The Cu-graphene system shows an increase
      in differential conductance for more contact area at a low bias voltage,
      primarily originating from the shift of transmission peaks relative to the Fermi
      energy. As the bias increases, there is an irregular change of conductance,
      including a weak negative differential conductance for more contact area. In
      contrast, the conductance of the Ni-graphene junction is monotonically enhanced
      with increasing overlap area. The minority spin which shows a broad transmission
      is responsible for the conductance increase of Ni-graphene. These behaviors can
      be attributed to different mechanisms of the interfacial electron transport:
      Charge transfer between graphene and Cu largely dominates the transmission
      enhancement of Cu-graphene, whereas hybridization between graphene and Ni states
      plays a more important role in the transmission enhancement of Ni-graphene. The
      different behaviors of transmission increase correlate with not only the strength
      of the graphene-metal interaction but also the location of metal d states. 

PMID- 23968104
TI  - A comparative study by the grand canonical Monte Carlo and molecular dynamics
      simulations on the squeezing behavior of nanometers confined liquid films.
AB  - Grand canonical Monte Carlo (GCMC) and liquid-vapor molecular dynamics (LVMD)
      simulations are performed to investigate the squeezing and phase transition of a
      simple liquid argon film confined between two solid surfaces. Simulation results
      show that the LVMD simulation is capable of capturing the major thermodynamic
      equilibrium states of the confined film, as predicted by the GCMC simulations.
      Moreover, the LVMD simulations reveal the non-equilibrium squeeze out dynamics of
      the confined film. The study shows that the solvation force hysteresis, observed
      in many surface force experiments, is attributed to two major effects. The first
      is related to the unstable jumps during the laying transitions of the confined
      film, in which the gradient of force profile is larger than the driving spring
      constant. The second effect is related to the squeeze out dynamics of the
      confined film even though the first effect is absent. In general, these two
      dynamic processes are non-equilibrium in nature and involve significant energy
      dissipations, resulting in the force hysteresis. 

PMID- 23968105
TI  - K+-hydration in a low-energy two-dimensional wetting layer on the basal surface
      of muscovite.
AB  - Density Functional Theory points to a key role of K(+) solvation in the low
      energy two-dimensional arrangement of water molecules on the basal surface of
      muscovite. At a coverage of 9 water molecules per 2 surface potassium ions, there
      is room to accommodate the ions into wetting layers wherein half of them are
      hydrated by 3 and the other half by 4 water molecules, with no broken H-bonds, or
      wherein all are hydrated by 4. Relative to the "fully connected network of H
      bonded water molecules" that Odelius et al. found to form "a cage around the
      potassium ions," the hydrating arrangements are several tens of meV/H2O better
      bound. Thus, low-temperature wetting on muscovite is not driven towards "ice
      like" hexagonal coordination. Instead, solvation forces dominate.

PMID- 23968106
TI  - Ozone and carbon trioxide synthesis by low energy ion implantation onto solid
      carbon dioxide and implications to astrochemistry.
AB  - Ion implantation experiments were carried out on amorphous (30 K) and crystalline
      (80 K) solid CO2 using both reactive (D(+), H(+)) and non-reactive (He(+)) ions,
      simulating different irradiation environments on satellite and dust grain
      surfaces. Such ion irradiation synthesized several new species in the ice
      including ozone (O3), carbon trioxide (CO3), and carbon monoxide (CO) the main
      dissociation product of carbon dioxide. The yield of these products was found to
      be strongly dependent upon the ion used for irradiation and the sample
      temperature. Ion implantation changes the chemical composition of the ice with
      recorded infrared spectra clearly showing the coexistence of D3h and C2v isomers
      of CO3, for the first time, in ion irradiated CO2 ice. 

PMID- 23968107
TI  - Hot carrier-selective chemical reactions on Ag(110).
AB  - Here, we show that the pathways, products, and efficiencies of reactions
      occurring on a metal surface can be spatially modulated by varying the type and
      energy of hot carriers produced by injecting tunneling electrons or holes from a
      scanning tunneling microscope tip into the metal surface. Control over the metal
      surface reactions was demonstrated for the large-scale dissociation reaction of
      O2 molecules on a Ag(110) surface. Hot electrons (or holes) transported through
      the metal surface to chemisorbed O2 selectively dissociated the molecule into two
      oxygen atoms separated along the [110] (or [001]) lattice direction. The reaction
      selectivity was enhanced compared to the selectivity of a direct reaction
      involving tunneling carriers. 

PMID- 23968108
TI  - First glimpse of the soft x-ray induced excited spin-state trapping effect
      dynamics on spin cross-over molecules.
AB  - The dynamics of the soft x-ray induced excited spin state trapping (SOXIESST)
      effect of Fe(phen)2(NCS)2 (Fe-phen) powder have been investigated by x-ray
      absorption spectroscopy (XAS) using the total electron yield method, in a wide
      temperature range. The low-spin (LS) state is excited into the metastable high
      spin (HS) state at a rate that depends on the intensity of the x-ray illumination
      it receives, and both the temperature and the intensity of the x-ray illumination
      will affect the maximum HS proportion that is reached. We find that the SOXIESST
      HS spin state transforms back to the LS state at a rate that is similar to that
      found for the light induced excited spin state trapping (LIESST) effect. We show
      that it is possible to use the SOXIESST effect in combination with the LIESST
      effect to investigate the influence of cooperative behavior on the dynamics of
      both effects. To investigate the impact of molecular cooperativity, we compare
      our results on Fe-phen with those obtained for Fe{[Me2Pyrz]3BH}2 (Fe-pyrz)
      powder, which exhibits a similar thermal transition temperature but with a
      hysteresis. We find that, while the time constant of the dynamic is identical for
      both molecules, the SOXIESST effect is less efficient at exciting the HS state in
      Fe-pyrz than in Fe-phen. 

PMID- 23968109
TI  - Directed translocation of a flexible polymer through a cone-shaped nano-channel.
AB  - Translocation of a flexible polymer through a cone-shaped channel is studied,
      theoretically and using computer simulations. Our simulations show that the shape
      of the channel causes the polymer translocation to be a driven process. The
      effective driving force of entropic origin acting on the polymer is calculated as
      a function of the length and the apex-angle of the channel, theoretically. It is
      found that the translocation time is a non-monotonic function of the apex-angle
      of the channel. By increasing the apex-angle from zero, the translocation time
      shows a minimum and then a maximum. Also, it is found that regardless of the
      value of the apex-angle, the translocation time is a uniformly decreasing
      function of the channel length. The results of the theory and the simulation are
      in good qualitative agreement. 

PMID- 23968110
TI  - Effects of attractive colloids on the phase separation behaviors of binary
      polymer blends.
AB  - The attractive colloids are added as fillers to control the phase behaviors of
      binary polymer blends. Because the colloids attract both components in the
      blends, aggregates are formed by the colloids coated with both kinds of polymer
      brushes. The aggregation results in two contradictory effects on the phase
      separation. First, the formation of aggregate decreases the translational
      entropy, which promotes the phase separation. On the other hand, the phase
      separation causes the extra free energy penalty due to the stretch of the chains
      attaching on the colloids, which prevents the phase separation. Furthermore, as
      the concentration or adsorbability of the colloids increases the local
      fluctuations within the aggregates become important. This results in a transition
      from the macro-phase separation to the micro-phase separation and the existence
      of the Lifshitz point. All of these effects lead to diverse phase behaviors in
      the polymer nanocomposites system. In present work, these behaviors are studied
      theoretically by the random phase approximation in a model system. 

PMID- 23968111
TI  - Effective diffusivity in transient state.
AB  - The effective diffusivity in a polymer matrix modified with inclusions is usually
      calculated based on Kalnin-Kotomin's model [J. R. Kalnin, E. A. Kotomin, and J.
      Maier, J. Phys. Chem. Solids 63, 449-456 (2002)], which extends the well known
      Maxwell-Garnett formula. Kalnin-Kotomin's model correctly predicts effective
      diffusivity for stationary diffusion or for infinite media. In the present paper
      diffusion in composite media is studied for finite systems under transient
      conditions. The process of diffusion is modeled numerically and effective
      diffusion coefficient in the transient state is estimated, which, under certain
      conditions, is different from the predictions of the Kalnin-Kotomin's model. An
      analytical model is proposed to explain deviations of the transient effective
      coefficient of diffusion from the stationary case. 

PMID- 23968112
TI  - Driven transport of particles in 3D ordered porous media.
AB  - Brownian dynamics simulation has been employed to study the behavior of force
      driven particle transport in two different types of ordered porous media: (A)
      interconnected spherical cavities and (B) an array of spherical obstacles, both
      arranged in simple cubic lattice. The effects of the imposed field strength and
      direction on the particle mobility and diffusivity are investigated. At a given
      porosity and imposed field strength, the particle mobility is greater for Case B
      than for Case A, owing to a higher degree of pore openness for the former. While
      the normalized mobility always increases with the field strength for Case B,
      irrespective of the field direction, it decreases for Case A when the field is
      not aligned with an aperture line. The particle diffusion may become anisotropic
      and show a nonmonotonic behavior with varying field strength. The diffusivity may
      increase 10-fold under a field misaligned with an aperture line. 

PMID- 23968113
TI  - Photoelectron spectroscopic and density functional theoretical studies of the 2'
      deoxycytidine homodimer radical anion.
AB  - The intact (parent) 2'-deoxycytidine homodimer anion, (dC)2 (?-), was generated
      in the gas phase (in vacuo) using an infrared desorption/photoemission source and
      its photoelectron spectrum was recorded using a pulsed, magnetic bottle
      photoelectron spectrometer. The photoelectron spectrum (PES) revealed a broad
      peak with the maximum at an electron binding energy between 1.6 and 1.9 eV and
      with a threshold at ~1.2 eV. The relative energies and vertical detachment
      energies of possible anion radicals were calculated at the B3LYP/6-31++G(**)
      level of theory. The most stable anion radicals are the complexes involving
      combinations of the sugar[middle dot][middle dot][middle dot]base and base[middle
      dot][middle dot][middle dot]base interactions. The calculated adiabatic electron
      affinities and vertical detachment energies of the most stable (dC)2 (?-) anions
      agree with the experimental values. In contrast with previous experimental
      computational studies on the anionic complexes involving nucleobases with various
      proton-donors, the electron-induced proton transferred structures of (dC)2 (?-)
      are not responsible for the shape of PES. 

PMID- 23968114
TI  - Gibbs energies, enthalpies, and entropies of water and lysozyme at the inner edge
      of excess hydration.
AB  - The aim of this study is to simultaneously monitor the excess partial Gibbs
      energies, enthalpies, and entropies of water and white egg lysozyme and
      demonstrate how these quantities correlate with the coverage of the protein
      macromolecules by water molecules. Isothermal calorimetry and water sorption
      measurements were applied to characterize the hydration dependencies of the
      excess thermodynamic functions. The excess partial quantities are found to be
      sensitive to changes in the water and protein states. At the lowest water weight
      fractions (w1), changes in the excess functions are primarily attributable to the
      addition of water. The transition of lysozyme from a glassy (rigid) to a flexible
      (elastic) state is accompanied by significant changes in the excess partial
      quantities. When the charged groups on the protein are covered, this transition
      occurs at w1 = 0.05; when the coverage of both polar and weakly interacting
      surface elements is complete, the excess partial quantities become hydrated at w1
      > 0.5. At the highest water content, water addition has no significant effect on
      the excess quantities. At w1 > 0.5, changes in the excess functions solely
      reflect changes in the state of the protein. 

PMID- 23968115
TI  - Molecular dynamics simulation of a single-stranded DNA with heterogeneous
      distribution of nucleobases in aqueous medium.
AB  - The DNA metabolic processes often involve single-stranded DNA (ss-DNA) molecules
      as important intermediates. In the absence of base complementarity, ss-DNAs are
      more flexible and interact strongly with water in aqueous media. Ss-DNA-water
      interactions are expected to control the conformational flexibility of the DNA
      strand, which in turn should influence the properties of the surrounding water
      molecules. We have performed room temperature molecular dynamics simulation of an
      aqueous solution containing the ss-DNA dodecamer, 5'-CGCGAATTCGCG-3'. The
      conformational flexibility of the DNA strand and the microscopic structure and
      ordering of water molecules around it have been explored. The simulation reveals
      transformation of the initial base-stacked form of the ss-DNA to a fluctuating
      collapsed coil-like conformation with the formation of a few non-sequentially
      stacked base pairs. A preliminary analysis shows further collapse of the DNA
      conformation in presence of additional salt (NaCl) due to screening of negative
      charges along the backbone by excess cations. Additionally, higher packing of
      water molecules within a short distance from the DNA strand is found to be
      associated with realignment of water molecules by breaking their regular
      tetrahedral ordering. 

PMID- 23968120
TI  - Clinical and dermoscopic patterns of melanocytic nevi in Hispanic adolescents: a
      descriptive study.
AB  - BACKGROUND: Melanocytic nevi are well-known, important precursors of melanoma
      among children and adults. The adolescence period is an important period for nevi
      formation and evolution. This study provides data of a longitudinal study of nevi
      in a Hispanic adolescent population. MATERIALS AND METHODS: A cross-sectional
      survey and 1-year prospective follow-up study was performed on Hispanic students
      from grades 6 and 7 at a school in Caguas, Puerto Rico (n = 90). The survey was
      completed by the students and one of their parents. The backs of the children
      were clinically examined for melanocytic nevi using digital photography and
      dermoscopy. Follow-up was conducted one year later. RESULTS: The study cohort
      consisted of 53 (59%) boys and 37 (41%) girls, with an average age of 11.9 years
      (range 11-13 years). At the beginning of the study, 85% (n = 71/90) of the
      students presented with melanocytic nevi on their backs. After one year, new nevi
      were identified in 62% (n = 44/71), and there was a mean increase in nevus count
      of 1.8 (P < 0.001). A trend toward increased nevus count in lighter skin types
      was observed (P < 0.001). The predominant dermoscopic pattern was reticular
      (44%). The globular pattern was found most commonly in children with skin-type II
      (100%), while the reticular pattern was the most common among skin-types III
      (32%), IV (56%), and V (45%). CONCLUSIONS: This study supports the utility of
      digital photography and dermoscopy for the evaluation of melanocytic nevi,
      providing evidence of the interrelationship between nevus count, dermoscopic
      pattern, and skin phenotype.

PMID- 23968121
TI  - Diffusion tensor imaging in SPG11- and SPG4-linked hereditary spastic paraplegia.
AB  - The aim of this study was to identify potential diagnostic markers of Hereditary
      Spastic Paraplegia (HSP). We investigated the white matter features of spastic
      gait (SPG)11- and SPG4-linked HSP, using diffusion tensor imaging performed with
      a 3-Tesla (3T) scanner. We examined four patients with SPG11 mutations, three
      with SPG4 mutations, and 26 healthy controls. We obtained maps of fractional
      anisotropy (FA) and mean diffusivity (MD), which we analyzed through both region
      of interest -based approach and tract-based spatial statistics (TBSS). Compared
      with healthy controls, SPG11 patients presented increased MD and decreased FA in
      the semioval centers, frontal and peritrigonal white matter, posterior limb of
      the internal capsule, and throughout the corpus callosum. Similar alterations
      were seen in the SPG4 patients at the levels of the semioval centers, the
      posterior limb of the internal capsule, the left cerebral pedicle, the genu and
      trunk of the corpus callosum, and the peritrigonal white matter on the left. No
      MD or FA alterations were observed in the cerebellar white matter. In a direct
      comparison, white matter alterations were more pronounced and widespread in HSP
      SPG11 than in HSP-SPG4 patients. Joint TBSS analysis of all three groups
      confirmed significant widespread alterations of FA and MD values in the
      supratentorial white matter. This noninvasive study documented the presence of
      altered diffusivity in white matter in both forms of HSP, which could represent
      an important diagnostic marker of HSP. The association of reduced FA and
      increased MD in this patient population supports the interpretation of HPG as a
      neurodegenerative disorder. 

PMID- 23968122
TI  - Peripheral inflammatory activation after hippocampus irradiation in the rat.
AB  - PURPOSE: To detect the possible biochemical signs of inflammatory activation in
      the peripheral circulation in a rodent model of hippocampus irradiation, and to
      examine the effects of L-alpha-glycerylphosphorylcholine (GPC) in this
      experimental protocol. MATERIALS AND METHODS: Anesthetized Sprague-Dawley rats
      were subjected to 40 Gy cobalt irradiation of both hemispheres of the
      hippocampus, with or without GPC treatment (50 mg/kg intravenously (i.v.), 5 min
      before the irradiation, n = 6, each). A third group (n = 6) served as saline
      treated control. Blood samples were obtained 3 h after the end of irradiation in
      order to examine the changes in plasma histamine, tumor necrosis factor-alpha
      (TNF-alpha), interleukin 1-beta, interleukin 6 (IL-6) and interleukin 10 (IL-10);
      liver tissue samples were taken to determine adenosine triphosphate (ATP)
      concentrations. RESULTS: The hepatic ATP levels were significantly declined,
      while plasma concentrations of circulating TNF-alpha, IL-6, IL-10 and histamine
      were significantly increased after hippocampus irradiation. GPC treatment
      significantly reduced the irradiation-induced release of cytokines and histamine,
      and the liver ATP level was maintained at the control value. CONCLUSIONS:
      Targeted brain irradiation produced measurable pro- and anti-inflammatory
      cytokine changes in the systemic circulation. GPC supplementation provides
      significant protection against irradiation-induced peripheral pro-inflammatory
      activation and ATP depletion.

PMID- 23968124
TI  - Toward a noncomputational cognitive neuroscience.
AB  - The near universally accepted theory that the brain processes information
      persists in current neural network theory where there is "subsymbolic"
      computation (Smolensky, 1988) on distributed representations. This theory of
      brain information processing may suffice for simplifying models simulated in
      silicon but not for living neural nets where there is ongoing chemical tuning of
      the input/output transfer function at the nodes, connection weights, network
      parameters, and connectivity. Here the brain continually changes itself as it
      intersects with information from the outside. An alternative theory to
      information processing is developed in which the brain permits and supports
      "participation" of self and other as constraints on the dynamically evolving,
      self-organizing whole. The noncomputational process of "differing and deferring"
      in nonlinear dynamic neural systems is contrasted with Black's (1991) account of
      molecular information processing. State hyperspace for the noncomputational
      process of nonlinear dynamical systems, unlike classical systems, has a fractal
      dimension. The noncomputational model is supported by suggestive evidence for
      fractal properties of the brain. 

PMID- 23968125
TI  - Functional Associations among Human Posterior Extrastriate Brain Regions during
      Object and Spatial Vision.
AB  - Primate extrastriate visual cortex is organized into an occipitotemporal pathway
      for object vision and an occipitoparietal pathway for spatial vision.
      Correlations between normalized regional cerebral blood flow values (regional
      divided by global flows), obtained using H2(15)O and positron emission
      tomography, were used to examine functional associations among posterior brain
      regions for these two pathways in 17 young men during performance of a face
      matching task and a dot-location matching task. During face matching, there was a
      significant correlation in the right hemisphere between an extrastriate occipital
      region that was equally activated during both the face matching and dot-location
      matching tasks and a region in inferior occipitotemporal cortex that was
      activated more during the face matching task. The corresponding correlation in
      the left hemisphere was not significantly different from zero. Significant
      intrahemispheric correlations among posterior regions were observed more often
      for the right than for the left hemisphere. During dot-location matching, many
      significant correlations were found among posterior regions in both hemispheres,
      but significant correlations between specific regions in occipital and parietal
      cortex shown to be reliably activated during this spatial vision test were found
      only in the right cerebral hemisphere. These results suggest that (1)
      correlational analysis of normalized rCBF can detect functional interactions
      between components of proposed brain circuits, and (2) face and dot-location
      matching depend primarily on functional interactions between posterior cortical
      areas in the right cerebral hemisphere. At the same time, left hemisphere
      cerebral processing may contribute more to dot-location matching than to face
      matching. 

PMID- 23968126
TI  - Computational Consequences of a Bias toward Short Connections.
AB  - A fundamental observation in the neurosciences is that the brain is a modular
      system in which different regions perform different tasks. Recent evidence,
      however, raises questions about the accuracy of this characterization with
      respect to neo-nates. One possible interpretation of this evidence is that
      certain aspects of the modular organization of the adult brain arise
      developmentally. To explore this hypothesis we wish to characterize the
      computational principles that underlie the development of modular systems. In
      previous work we have considered computational schemes that allow a learning
      system to discover the modular structure that is present in the environment
      (Jacobs, Jordan, & Barto, 1991). In the current paper we present a complementary
      approach in which the development of modularity is due to an architectural bias
      in the learner. In particular, we examine the computational consequences of a
      simple architectural bias toward short-range connections. We present simulations
      that show that systems that learn under the influence of such a bias have a
      number of desirable properties, including a tendency to decompose tasks into
      subtasks, to decouple the dynamics of recurrent subsystems, and to develop
      location-sensitive internal representations. Furthermore, the system's units
      develop local receptive and projective fields, and the system develops
      characteristics that are typically associated with topographic maps. 

PMID- 23968127
TI  - Selective interference with the representation of size in the human by direct
      cortical electrical stimulation.
AB  - A specific category in human cognition, size representation, was disrupted by the
      application of cortical electrical interference through a recently modified
      technique involving implantation of indwelling subdural electrode arrays. When
      subjected to electrical stimulation at a specific site, the subject was unable to
      access size information when questioned verbally, but showed no deficit if the
      size discrimination was presented visually. Verbal questions about size were
      answered correctly when the patient was not subjected to cortical interference.
      Other measures of verbal and visual comprehension for the categories of color,
      shape, orientation, movement, texture, and structure, tested under cortical
      interference, were normal. This clear-cut distinction between verbal and visual
      access to information about size, shown by a reversible block at a known and
      anatomically circumscribed site, provides further evidence that higher order
      neural processing is categorically represented. 

PMID- 23968123
TI  - Treating symptomatic hyperprolactinemia in women with schizophrenia: presentation
      of the ongoing DAAMSEL clinical trial (Dopamine partial Agonist, Aripiprazole,
      for the Management of Symptomatic ELevated prolactin).
AB  - Prolactin elevations occur in people treated with antipsychotic medications and
      are often much higher in women than in men. Hyperprolactinemia is known to cause
      amenorrhea, oligomenorrhea, galactorrhea and gynecomastia in females and is also
      associated with sexual dysfunction and bone loss. These side effects increase
      risk of antipsychotic nonadherence and suicide and pose significant problems in
      the long term management of women with schizophrenia. In this manuscript, we
      review the literature on prolactin; its physiology, plasma levels, side effects
      and strategies for treatment. We also present the rationale and protocol for an
      ongoing clinical trial to treat symptomatic hyperprolactinemia in premenopausal
      women with schizophrenia. More attention and focus are needed to address these
      significant side effects and help the field better personalize the treatment of
      women with schizophrenia. 

PMID- 23968128
TI  - Visual Processing without Awareness: Evidence from Unilateral Neglect.
AB  - Can visual processing be carried out without visual awareness of the presented
      objects? In the present study we addressed this problem in patients with severe
      unilateral neglect. The patients were required to respond as fast as possible to
      target stimuli (pictures of animals and fruits) presented to the normal field by
      pressing one of the two keys according to the category of the targets. We then
      studied the influence of priming stimuli, again pictures of animals or fruits,
      presented to the neglected field on the responses to targets. By combining
      different pairs of primes and targets, three different experimental conditions
      were obtained. In the first condition, "Highly congruent," the target and prime
      stimuli belonged to the same category and were physically identical; in the
      second condition, "Congruent," the stimuli represented two elements of the same
      category but were physically dissimilar; in the third condition, "Noncongruent,"
      the stimuli represented one exemplar from each of the two categories of stimuli.
      The results showed that the responses were facilitated not only in the Highly
      congruent condition, but also in the Congruent one. This finding suggests that
      patients with neglect are able to process stimuli presented to the neglected
      field to a categorical level of representation even when they deny the stimulus
      presence in the affected field. The implications of this finding for
      psychological and physiological theory of neglect and visual cognition are
      discussed. 

PMID- 23968129
TI  - Human cerebral cortex: localization, parcellation, and morphometry with magnetic
      resonance imaging.
AB  - We describe a system of parcellation of the human brain that is based on the
      functional anatomy of the cerebral cortex and that is applied to the analysis of
      magnetic resonance images. This system is designed to support investigations of
      hemispheric asymmetries and quantitative lesion localization studies in cognitive
      neuroscience. The system of cortical subdivision is a neural systems oriented
      model that approximates subdivisions supported by previous architectonic and
      functional analyses. It is based primarily on boundaries determined by "limiting
      fissures." It is completed by a set of coronal planes, keyed to visible anatomic
      landmarks, which "close" the borders of the parcellation subdivisions. The method
      depends on computational reconstruction of the primary image data in multiple
      planes so as to allow the observed pattern of limiting fissures in a given brain
      to be digitized. In this presentation, the method is applied in order to define
      the surface anatomy of the cerebral hemispheres in a normal subject. Volumetric
      measurements of individual cortical regions are compared as hemispheric
      percentiles to areal perceniiles derived from the analysis of Jouandet et al.
      (1989), a conceptually related though methodologically different approach. We
      specifically address the approach to the study of interhemispheric differences
      and interindividual variations in cortical anatomy. 

PMID- 23968130
TI  - Brain Potentials during Memory Retrieval Provide Neurophysiological Support for
      the Distinction between Conscious Recollection and Priming.
AB  - Event-related brain potentials were recorded from subjects as they attempted to
      identify words displayed tachistoscopically. Words that had also been presented a
      few minutes earlier in a different context were identified more often than were
      words that had not been presented before. This priming effect was observed for
      words initially seen in an imagery task requiring size estimations as well as for
      words initially seen in an orthographic task requiring letter counting. Unlike
      priming, recall and recognition were much better for words repeated from the
      imagery task than from the orthographic task. Brain potentials elicited during
      word identification also differed as a function of task. Based on these
      differences, a potential from 500 to 800 msec was interpreted as an index of
      recollection processes. Earlier potentials may have indexed processing related to
      priming. These effects thus provide measures of the hypothetical processes
      underlying memory performance and demonstrate that recollection and priming are
      associated with distinct neural events. 

PMID- 23968131
TI  - Dirac fermion heating, current scaling, and direct insulator-quantum Hall
      transition in multilayer epitaxial graphene.
AB  - We have performed magnetotransport measurements on multilayer epitaxial graphene.
      By increasing the driving current I through our graphene devices while keeping
      the bath temperature fixed, we are able to study Dirac fermion heating and
      current scaling in such devices. Using zero-field resistivity as a self
      thermometer, we are able to determine the effective Dirac fermion temperature
      (TDF) at various driving currents. At zero field, it is found that TDF ? I~1/2.
      Such results are consistent with electron heating in conventional two-dimensional
      systems in the plateau-plateau transition regime. With increasing magnetic field
      B, we observe an I-independent point in the measured longitudinal resistivity
      rhoxx which is equivalent to the direct insulator-quantum Hall (I-QH) transition
      characterized by a temperature-independent point in rhoxx. Together with recent
      experimental evidence for direct I-QH transition, our new data suggest that such
      a transition is a universal effect in graphene, albeit further studies are
      required to obtain a thorough understanding of such an effect. 

PMID- 23968133
TI  - A family of layered chiral porous magnets exhibiting tunable ordering
      temperatures.
AB  - A simple change of the substituents in the bridging ligand allows tuning of the
      ordering temperatures, Tc, in the new family of layered chiral magnets
      A[M(II)M(III)(X2An)3].G (A = [(H3O)(phz)3](+) (phz = phenazine) or NBu4(+);
      X2An(2-) = C6O4X2(2-) = 2,5-dihydroxy-1,4-benzoquinone derivative dianion, with
      M(III) = Cr, Fe; M(II) = Mn, Fe, Co, etc.; X = Cl, Br, I, H; G = water or
      acetone). Depending on the nature of X, an increase in Tc from ca. 5.5 to 6.3,
      8.2, and 11.0 K (for X = Cl, Br, I, and H, respectively) is observed in the MnCr
      derivative. Furthermore, the presence of the chiral cation [(H3O)(phz)3](+),
      formed by the association of a hydronium ion with three phenazine molecules,
      leads to a chiral structure where the Delta-[(H3O)(phz)3](+) cations are always
      located below the Delta-[Cr(Cl2An)3](3-) centers, leading to a very unusual
      localization of both kinds of metals (Cr and Mn) and to an eclipsed disposition
      of the layers. This eclipsed disposition generates hexagonal channels with a void
      volume of ca. 20% where guest molecules (acetone and water) can be reversibly
      absorbed. Here we present the structural and magnetic characterization of this
      new family of anilato-based molecular magnets. 

PMID- 23968132
TI  - Structures of the excited states of phospholamban and shifts in their populations
      upon phosphorylation.
AB  - Phospholamban is an integral membrane protein that controls the calcium balance
      in cardiac muscle cells. As the function and regulation of this protein require
      the active involvement of low populated states in equilibrium with the native
      state, it is of great interest to acquire structural information about them. In
      this work, we calculate the conformations and populations of the ground state and
      the three main excited states of phospholamban by incorporating nuclear magnetic
      resonance residual dipolar couplings as replica-averaged structural restraints in
      molecular dynamics simulations. We then provide a description of the manner in
      which phosphorylation at Ser16 modulates the activity of the protein by
      increasing the sizes of the populations of its excited states. These results
      demonstrate that the approach that we describe provides a detailed
      characterization of the different states of phospholamban that determine the
      function and regulation of this membrane protein. We anticipate that the
      knowledge of conformational ensembles enable the design of new dominant negative
      mutants of phospholamban by modulating the relative populations of its
      conformational substates.

PMID- 23968135
TI  - Trp homozygotes at codon 64 of ADRB3 gene are protected against the risk of type
      2 diabetes in the Kashmiri population.
AB  - The prevalence of type 2 diabetes mellitus has reached epidemic proportions
      worldwide. Type 2 diabetes is a consequence of complex interactions among
      multiple genetic variants and environmental risk factors. Polymorphisms in
      various candidate genes confer susceptibility to diabetes. This study was
      undertaken to analyse a single nucleotide polymorphism Trp64Arg (C<->T) in the
      ADRB3 gene and elucidate its effects on type 2 diabetes and its associated risk
      factors. The study included 200 type 2 diabetes patients and 300 age and gender
      matched healthy controls belonging to the ethnic Kashmiri population. Polymerase
      chain reaction-restriction fragment length polymorphism technique was used for
      genotyping and the results were validated by direct sequencing assay. Genotypes
      for Trp64Arg polymorphism were in Hardy-Weinberg equilibrium (chi(2)=0.48, p=NS).
      Frequency of the Arg64 allele was 40% and 10.2% in cases and controls,
      respectively (p<0.05; odds ratio 5.89; 95% CI; 3.69-9.39). The Arg64 allele was
      directly related to higher body mass index, waist-to-hip ratio, dyslipidemia and
      uncontrolled disease status. The study signifies that the Arg64 allele of the
      ADRB3 gene is a genotypic risk factor and confers susceptibility to type 2
      diabetes, whereas the homozygous Trp64 genotype exerted a protective effect in
      our population. 

PMID- 23968134
TI  - Thymidylate synthase gene polymorphism and survival of colorectal cancer patients
      receiving adjuvant 5-fluorouracil.
AB  - Limited studies indicate a possible association of 5'-UTR thymidylate synthase
      enhancer region polymorphism and treatment outcome in patients medicated with 5
      fluorouracil (5-FU). The study was designed to verify the relationship in
      patients with colorectal cancer (CRC), a Polish population that received 5-FU
      based adjuvant chemotherapy. The study analyzed 145 Astler-Coller B2 and C CRC
      patients. Genotyping for a variable number of tandem repeats and G to C single
      nucleotide polymorphism in the 5'-UTR of the thymidylate synthase (TS) gene was
      carried out. TS genotypes were classified into high expression (high TS) and low
      expression types (low TS). High TS was found in 22.8% of patients. The right-side
      tumors were more frequently associated with high TS than the left-side tumors
      (p=0.024). High TS was only found in 9.3% of rectal tumors, but in 29.7% of colon
      cancers (p=0.0042). Disease-free survival after 20 months (DFS 20) was longer in
      subjects with low TS than in high TS (p=0.043). Patients who underwent
      chemotherapy had longer DFS 20 in the low TS than in the high TS subgroup
      (p=0.051). The low TS was found to be an independent good prognostic factor for
      DFS 20 in the whole group as well as in the subgroup treated with chemotherapy
      (p=0.024 and p=0.034, respectively). Patients with low TS did not show any
      differences in DFS 20 whether they were treated with adjuvant chemotherapy or
      not. Proximal CRC tumors are characterized by higher TS expression genotypes than
      distal tumors, and are at significantly greater risk of early recurrence during
      the first 20 months after surgery. 

PMID- 23968136
TI  - Small-angle neutron scattering study of structure and interaction of
      nanoparticle, protein, and surfactant complexes.
AB  - Small-angle neutron scattering (SANS) measurements have been carried out from the
      multicomponent system composed of Ludox HS40 silica nanoparticle, bovine serum
      albumin (BSA) protein, and sodium dodecyl sulfate (SDS) surfactant in an aqueous
      system under the solution condition that all the components are negatively
      charged. Although the components are similarly charged, strong structural
      evolutions among them have been observed. The complexes of different components
      in pairs (nanoparticle-protein, nanoparticle-surfactant, and protein-surfactant)
      have been examined to correlate the role of each component in the three-component
      nanoparticle-protein-surfactant system. The nanoparticle-protein system shows
      depletion interaction induced aggregation of nanoparticles in the presence of
      protein. Both nanoparticle and surfactant coexist individually in a nanoparticle
      surfactant system. In the case of a protein-surfactant system, the cooperative
      binding of surfactant with protein leads to micelle-like clusters of surfactant
      formed along the unfolded protein chain. The structure of the three-component
      (nanoparticle-protein-surfactant) system is found to be governed by the
      synergetic effect of nanoparticle-protein and protein-surfactant interactions.
      The nanoparticle aggregates coexist with the structures of protein-surfactant
      complex in the three-component system. The nanoparticle aggregation as well as
      unfolding of protein is enhanced in this system as compared to the corresponding
      two-component systems. 

PMID- 23968137
TI  - Adsorption and hydrolytic activity of the polycatalytic cellulase nanocomplex on
      cellulose.
AB  - The formation of polycatalytic enzyme complexes may enhance the effectiveness of
      enzymes due to improved substrate interaction and synergistic actions of multiple
      enzymes in proximity. Much effort has been made to develop highly efficient
      polycatalytic cellulase complexes by immobilizing cellulases on low-cost polymer
      or nanoparticle scaffolds, aiming at their potential applications in biomass
      conversion to fuels. However, some key cellulases carry out the hydrolytic
      reaction on crystalline cellulose in a directional, processive manner. A large,
      artificial polycatalytic complex is unlikely to undergo a highly coordinated
      motion to slide on the cellulose surface as a whole unit. The mechanism
      underlying the activity enhancements observed in some artificial cellulase
      complexes and the limit of this approach remain elusive. Herein, we report the
      synthesis of polycatalytic cellulase complexes bound to colloidal polymer
      nanoparticles with a magnetic core and describe their unique adsorption,
      hydrolytic activities, and motions on cellulose. The polycatalytic clusters of
      cellulases on colloidal polymers show an increased rate of hydrolytic reactions
      on cellulose, but this was observed mainly at relatively low cellulase-to
      cellulose ratios. Enhanced efficiency is mainly attributed to increased local
      concentrations of cellulases on the scaffolds and their polyvalent interactions
      with cellulose. However, once bound, the polycatalytic complexes can only carry
      out reactions locally and are not capable of relocating to new sites rapidly due
      to their lack of long-range surface mobility and their extremely tight binding.
      The development of highly optimized polycatalytic complexes may arise by
      developing novel nanoscaffolds that induce concerted motion of the complex as a
      whole. 

PMID- 23968138
TI  - Dermoscopic features of cutaneous leishmaniasis.
AB  - BACKGROUND: Previous studies have demonstrated that dermoscopy improves accuracy
      in diagnosing pigmented and non-pigmented tumors. Recently, there has been
      increasing evidence that dermoscopy can also be useful in the diagnosis of some
      skin infections. OBJECTIVE: We sought to describe the dermoscopic features of
      cutaneous leishmaniasis. METHOD: Dermoscopic examination (using the Derm Lite
      FOTO, 3Gen) of 144 CL lesions in 82 patients was performed. This study was
      conducted in the Imam Reza and Ghaem hospitals (Mashhad, Iran) from October 2010
      to September 2011. RESULTS: We observed the following dermoscopic features:
      generalized erythema (81.9%), white starbursts (60.4%), yellow hue (43.8%),
      yellow teardrop-like structures (41.7%), central ulcers (59%), hyperkeratosis
      (33.3%), and milia-like cysts (4.9%). We also observed vascular structures,
      including dotted vessels (61.1%), hairpin vessels (37.5%), linear irregular
      vessels (30.6%), comma-shaped vessels (29.9%), glomerular vessels (22.9%),
      arborizing telangiectasia (10.4%), and corkscrew vessels (4.2%). LIMITATIONS:
      Biopsy and pathologic evaluation were not performed due to ethical
      considerations. CONCLUSION: Important vascular patterns seen in melanocytic and
      non-melanocytic tumors were frequently observed in this infection. Dermoscopy may
      be a promising tool to predict the clinical course in cases of cutaneous
      leishmaniasis.

PMID- 23968139
TI  - Retinocollicular mapping explained?
AB  - We review and comment on the recent model of Grimbert and Cang of the development
      of topographically ordered maps from the retina to the superior colliculus. This
      model posits a phase in which arbors are created in zones permitted by Eph and
      ephrin signaling, followed by a phase in which activity-dependent synaptic
      plasticity refines the map. We show that it is not possible to generate the
      arborization probability functions used in the simulations of Grimbert and Cang
      using gradients of Ephs and ephrins and the interaction mechanism that Grimbert
      and Cang propose in their results. Furthermore, the arborization probabilities we
      do generate are far less sharp than we imagine truly "permissive" ones would be.
      It remains to be seen if maps can be generated from the nonpermissive
      arborization probabilities generated from gradients.

PMID- 23968141
TI  - Effect of DA-8031, a novel oral compound for premature ejaculation, on male rat
      sexual behavior.
AB  - OBJECTIVES: DA-8031 is a potent and selective serotonin transporter inhibitor
      developed for the treatment of premature ejaculation. The aim of the present
      study was to investigate the effects of DA-8031 on male sexual behavior in a rat
      model. METHODS: Sexual behavior was examined after an acute oral administration
      of 10, 30 or 100 mg/kg of DA-8031 in copulation studies with female rats.
      Pharmacokinetic parameters were calculated after oral administration of DA-8031
      at a dose level of 30 mg/kg. RESULTS: DA-8031 treatment produced a dose-dependent
      increase in ejaculation latency time and showed statistical significance at 30
      and 100 mg/kg dosage levels compared with the vehicle (P < 0.05). In addition, DA
      8031 treatment reduced the mean number of ejaculations in a dose-dependent
      manner. No changes in post-ejaculatory interval, numbers of mounts, intromissions
      or ejaculations were observed at any dose. In pharmacokinetic study, the blood
      concentration of DA-8031 peaked at 0.38 +/- 0.14 h after oral administration, and
      then rapidly declined with a half-life of 1.79 +/- 0.32 h. CONCLUSIONS: Treatment
      with DA-8031 delays the ejaculation latency time without affecting the initiation
      of mounting behavior or post-ejaculatory interval in rats. Furthermore, DA-8031
      is rapidly absorbed and eliminated after oral administration in rats. These
      preclinical findings provide a clue for the clinical testing of DA-8031 as an "on
      demand" agent for premature ejaculation.

PMID- 23968140
TI  - Barriers and facilitators to implement shared decision making in
      multidisciplinary sciatica care: a qualitative study.
AB  - BACKGROUND: The Dutch multidisciplinary sciatica guideline recommends that the
      team of professionals involved in sciatica care and the patient together decide
      on surgical or prolonged conservative treatment (shared decision making [SDM]).
      Despite this recommendation, SDM is not yet integrated in sciatica care. Existing
      literature concerning barriers and facilitators to SDM implementation mainly
      focuses on one discipline only, whereas multidisciplinary care may involve other
      barriers and facilitators, or make these more complex for both professionals and
      patients. Therefore, this qualitative study aims to identify barriers and
      facilitators perceived by patients and professionals for SDM implementation in
      multidisciplinary sciatica care. METHODS: We conducted 40 semi-structured
      interviews with professionals involved in sciatica care (general practitioners,
      physical therapists, neurologists, neurosurgeons, and orthopedic surgeons) and
      three focus groups among patients (six to eight per group). The interviews and
      focus groups were audiotaped and transcribed in full. Reported barriers and
      facilitators were classified according to the framework of Grol and Wensing. The
      software package Atlas.ti 7.0 was used for analysis. RESULTS: Professionals
      reported 53 barriers and 5 facilitators, and patients 35 barriers and 18
      facilitators for SDM in sciatica care. Professionals perceived most barriers at
      the level of the organizational context, and facilitators at the level of the
      individual professional. Patients reported most barriers and facilitators at the
      level of the individual professional. Several barriers and facilitators
      correspond with barriers and facilitators found in the literature (e.g., lack of
      time, motivation) but also new barriers and facilitators were identified. Many of
      these new barriers mentioned by both professionals and patients were related to
      the multidisciplinary setting, such as lack of visibility, lack of trust in
      expertise of other disciplines, and lack of communication between disciplines.
      CONCLUSIONS: This study identified barriers and facilitators for SDM in the
      multidisciplinary sciatica setting, by both professionals and patients. It is
      clear that more barriers than facilitators are perceived for implementation of
      SDM in sciatica care. Newly identified barriers and facilitators are related to
      the multidisciplinary care setting. Therefore, an effective implementation
      strategy of SDM in a multidisciplinary setting such as in sciatica care should
      focus on these barriers and facilitators.

PMID- 23968142
TI  - Headspace-solid phase microextraction-gas chromatography-tandem mass spectrometry
      (HS-SPME-GC-MS2) method for the determination of pyrazines in perilla seed oils:
      impact of roasting on the pyrazines in perilla seed oils.
AB  - A new headspace (HS)-solid phase microextraction (SPME)-gas chromatography-tandem
      quadrupole mass spectrometry (GC-MS(2)) was established for the simultaneous
      characterization and quantitation of pyrazines in perilla seed oils. HS-SPME
      conditions such as fiber choice, extraction temperature, and adsorption times
      were tested. The established GC-MS(2) showed low detection limit (LOD) and high
      specificity, recovery, and precision for analysis of pyrazines in perilla seed
      oils. The LODs for the pyrazines were in the range of 0.07-22.22 ng/g oil. The
      relative standard deviations (RSDs) for the intra- and interday repeated analyses
      of pyrazines were less than 9.49 and 9.76%, respectively. The mean recoveries for
      spiked pyrazines in perilla seed oil were in the range of 94.6-107.92%. Perilla
      seed oils were obtained by mechanical pressing from perilla seeds roasted to
      different degrees of roasting (mild, medium, medium dark, and dark roasting).
      Fourteen pyrazine compounds in perilla seed oils were isolated, identified, and
      quantitated. Among them, 2-methyl-3-propylpyrazine, tetramethylpyrazine, and 2,3
      diethyl-5-methylpyrazine were the first identified in perilla seed oils. Degree
      of roasting influenced greatly the composition and contents of pyrazines in
      perilla seed oils. In light-roasted perilla seed oil, 2,5-dimethylpyrazine was
      the most predominant pyrazine. However, in dark-roasted perilla seed oil, 2
      methylpyrazine was the most abundant pyrazine in the oil, representing 38.3% of
      its total pyrazine content. Dark-roasted perilla seed oil contains 16.78 times
      higher quantity of pyrazines than light-roasted perilla seed oil. This represents
      the first report on the quantity of pyrazines in perilla seed oils. 

PMID- 23968143
TI  - Differential expression analysis with global network adjustment.
AB  - BACKGROUND: Large-scale chromosomal deletions or other non-specific perturbations
      of the transcriptome can alter the expression of hundreds or thousands of genes,
      and it is of biological interest to understand which genes are most profoundly
      affected. We present a method for predicting a gene's expression as a function of
      other genes thereby accounting for the effect of transcriptional regulation that
      confounds the identification of genes differentially expressed relative to a
      regulatory network. The challenge in constructing such models is that the number
      of possible regulator transcripts within a global network is on the order of
      thousands, and the number of biological samples is typically on the order of 10.
      Nevertheless, there are large gene expression databases that can be used to
      construct networks that could be helpful in modeling transcriptional regulation
      in smaller experiments. RESULTS: We demonstrate a type of penalized regression
      model that can be estimated from large gene expression databases, and then
      applied to smaller experiments. The ridge parameter is selected by minimizing the
      cross-validation error of the predictions in the independent out-sample. This
      tends to increase the model stability and leads to a much greater degree of
      parameter shrinkage, but the resulting biased estimation is mitigated by a second
      round of regression. Nevertheless, the proposed computationally efficient "over
      shrinkage" method outperforms previously used LASSO-based techniques. In two
      independent datasets, we find that the median proportion of explained variability
      in expression is approximately 25%, and this results in a substantial increase in
      the signal-to-noise ratio allowing more powerful inferences on differential gene
      expression leading to biologically intuitive findings. We also show that a large
      proportion of gene dependencies are conditional on the biological state, which
      would be impossible with standard differential expression methods. CONCLUSIONS:
      By adjusting for the effects of the global network on individual genes, both the
      sensitivity and reliability of differential expression measures are greatly
      improved.

PMID- 23968144
TI  - Cytosolic and mitochondrial ROS: which one is associated with poor chromatin
      remodeling?
AB  - The aim of this study was to determine if there are any associations between
      impaired chromatin packaging and the origin of reactive oxygen species (ROS)
      production. Cytosolic ROS, mitochondrial ROS, DNA protamination, and apoptosis
      were evaluated with dichlorofluoresceindiacetate (DCFH-DA), dihydrorhodamine 123
      (DHR123), chromomycin A3 (CMA3), and YO-Pro-1 (Y1)/propidium iodide (PI),
      respectively, by flow cytometry (FCM) in 40 infertile individuals. Percentages
      DCF+ and R123+ sperm were positively associated with percentage CMA3+ sperm and
      negatively associated with percentage apoptotic sperm. No correlation was
      observed between CMA3+ sperm and the percentage of apoptotic sperm. Under
      protamination of sperm is not associated with the origin of ROS production, but
      their relationship may suggest an association with general physiological
      dysfunction of sperm. Furthermore, under protamination does make sperm prone to
      apoptosis. Rather, it is likely that apoptosis is induced by ROS production.
      Considering that these conclusions are derived from correlative analyses,
      additional studies including an interventive approach are required. 

PMID- 23968145
TI  - A case of idiopathic follicular mucinosis treated with bexarotene gel.
AB  - BACKGROUND: Topical bexarotene 1% gel is currently FDA-approved for early stage
      (IA and IB) persistent or refractory cutaneous T-cell lymphoma (CTCL). No
      uniformly effective therapy exists for follicular mucinosis, although several
      treatments are routinely used. There are no known reports of topical bexarotene
      being used in the treatment of idiopathic follicular mucinosis when there is no
      association with CTCL. This article reports the first case of bexarotene gel to
      successfully treat persistent idiopathic follicular mucinosis. MATERIALS AND
      METHODS: This study describes a 34-year-old Caucasian male with idiopathic
      follicular mucinosis. The patient had treatment failure with clobetasol 0.05%
      ointment and narrow-band UVB. Intralesional injections with triamcinolone 5 mg/ml
      were successful for treating the plaques in the beard area. The patient was
      treated with bexarotene 1% gel applied twice a day to the persistent plaques on
      the lower extremities. The patient reported significant improvement in hair
      growth after only six weeks of treatment. The treatment was decreased to once a
      day due to erythema, and he had complete hair regrowth at 26 weeks. DISCUSSION:
      Several treatments have been described in the literature, such as
      corticosteroids, psoralen plus ultraviolet A (PUVA) light therapy, topical
      nitrogen mustard, and radiation therapy. Isolated cases have documented the
      beneficial responses of pimecrolimus, dapsone, indomethacin, minocycline,
      isotretinoin, hydroxychloroquine and interferons. No single treatment has been
      shown to be consistently effective. CONCLUSION: Topical bexarotene 1% gel should
      be considered for patients with idiopathic follicular mucinosis resistant to
      standard treatment.

PMID- 23968146
TI  - Predictors of re-canalisation in acute cerebral infarction from occlusion of the
      terminal internal carotid artery or of the middle cerebral artery mainstem
      treated with thrombolysis.
AB  - OBJECTIVE: We have evaluated the factors of unsuccessful re-canalisation in a
      large series of patients with hemispheric cerebral infarction treated with
      thrombolysis. PATIENTS AND METHODS: All patients aged 18-80 years with an acute
      hemispheric infarction, admitted within the first few hours of symptoms onset,
      were immediately submitted to Magnetic Resonance both Imaging (MRI) and
      Angiography (MRA). MRI and MRA were repeated at 24 h of stroke. Re-canalisation
      was attributed if grade 2 or 3 of Thrombolysis in Myocardial Infarction (TIMI)
      criteria for the myocardial infarction. Outcome was rated at three months of
      stroke. Re-canalisation was matched with ageing and with the common risk factors
      for stroke. RESULTS: One hundred and twenty-one patients, 70 men and 51 women,
      with a median age of 67 years, were included. Re-canalisation was seen in 62
      patients (51%). Twenty-three patients (19%) died by 90 days of stroke. Re
      canalisation was associated to survival (1 death vs. 22, p < 0.0001). Regression
      analysis retained advanced age (Odds ratio 0.37, 95% Confidence interval 0.13
      0.98), baseline National Institute of Health Stroke Scale (NIHSS) (Odds ratio
      0.94, 95% Confidence interval 0.89-0.98) and diabetes mellitus (Odds ratio 0.28,
      95% Confidence interval 0.09-0.84) as factors contrasting re-canalisation.
      CONCLUSIONS: Our study indicates that in patients with proven occlusion of the
      terminal segment of the internal carotid artery and/or of the mainstem of the
      Middle Cerebral Artery, re-canalisation at 24 h of the acute ischemic stroke is
      dramatically associated with survival, and halted by advanced age and diabetes
      mellitus.

PMID- 23968149
TI  - Global precedence, spatial frequency channels, and the statistics of natural
      images.
AB  - A great deal of evidence suggests that early in processing, retinal images are
      filtered by parallel, spatial frequency selective channels. We attempt to
      incorporate this view of early vision with the principle of global precedence,
      which holds that Gestalt-like processes sensitive to global image configurations
      tend to dominate local feature processing in human pattern perception. Global
      precedence is inferred from the pattern of reaction times observed when visual
      patterns contain multiple cues at different levels of spatial scale.
      Specifically, it is frequently observed that global processing times are largely
      unaffected by conflicting local cues, but local processing times are
      substantially lengthened by conflicting global cues. The asymmetry of these
      effects suggests the dominant role of global configurations. Since global spatial
      information is effectively represented by low spatial frequencies, global
      precedence potentially implies a low frequency dominance. The thesis is that low
      spatial frequencies tend to be available before information carried by higher
      frequency bands, producing a coarse-to-fine temporal order in visual spatial
      perception. It is suggested that a variety of factors contribute to the "prior
      entry" of low frequency information, including the high contrast gain of the
      magnocellular pathway, the amplitude spectra typical of natural images, and
      inhibitory interactions between the parallel frequency-tuned channels. Evidence
      suggesting a close relationship between global precedence and spatial frequency
      channels is provided by observations that the essential features of the global
      precedence effect are obtained using patterns consisting of low and high
      frequency sinusoids. The hypothesis that these asymmetric interference effects
      are due to interactions between parallel spatial channels is supported by an
      analysis of reaction times (RTs), which shows that RTs to redundant low and high
      frequency cues produce less facilitation than predictions that assume the
      channels are independent. In view of previous work showing that global precedence
      depends upon the low frequency content of the stimuli, we suggest that low
      spatial frequencies represent the sine qua non for the dominance of
      configurational cues in human pattern perception, and that this configurational
      dominance reflects the microgenesis of visual pattern perception. This general
      view of the temporal dynamics of visual pattern recognition is discussed, is
      considered from an evolutionary perspective, and is related to certain
      statistical regularities in natural scenes. Potential adaptive advantages of an
      interactive parallel architecture that confers an initial processing advantage to
      low resolution information are explored. 

PMID- 23968148
TI  - Work-related violence and inconsistent condom use with non-paying partners among
      female sex workers in Adama City, Ethiopia.
AB  - BACKGROUND: Although reported condom use between female sex workers and their
      clients is high in Ethiopia, condom use with regular, non-paying partners remains
      low, posing a substantial risk of HIV infection to sex workers, their partners
      and the general population. Previous studies have identified the synergistic
      effects of substance abuse, violence and HIV risk, but few have examined these
      inter-relationships among female sex workers and their regular, non-paying
      partners. This study explored the associations between work-related violence,
      alcohol abuse and inconsistent condom use among establishment-based female sex
      workers and their regular, non-paying partners in Adama City, Ethiopia. METHODS:
      A cross-sectional survey was conducted with 350 establishment-based female sex
      workers, aged 15-35, at 63 bars, hotels and nightclubs. Multivariate logistic
      regression analysis was conducted to test the association between work-related
      violence and condom use with regular, non-paying partners, controlling for age,
      overall income, education and sex workers' total number of sexual partners in the
      past week. Alcohol abuse was explored as an effect modifier. RESULTS: Respondents
      reported a high prevalence of work-related violence (59%) and alcohol abuse
      (51%). Work-related violence was statistically significantly associated with
      unprotected sex with regular, non-paying partners among those who abused alcohol
      (OR: 6.34, 95% CI: 2.43-16.56) and among those who did not (OR: 2.98, 95% CI:
      1.36-6.54). Alcohol abuse was not associated with inconsistent condom use within
      these partnerships, though it may strengthen the effect of work-related violence
      on unprotected sex. CONCLUSIONS: Findings suggest violence against establishment
      based female sex workers is associated with HIV risk within regular, non-paying
      partnerships. Qualitative work is needed to better understand the links between a
      violent work environment and condom use with regular, non-paying partners and how
      interventions can be implemented in this context to prevent violence against sex
      workers and reduce HIV transmission.

PMID- 23968150
TI  - Maturational Constraints on Functional Specializations for Language Processing:
      ERP and Behavioral Evidence in Bilingual Speakers.
AB  - Changes in several postnatal maturational processes during neural development
      have been implicated as potential mechanisms underlying critical period
      phenomena. Lenneberg hypothesized that maturational processes similar to those
      that govern sensory and motor development may also constrain capabilities for
      normal language acquisition. Our goal, using a bilingual model, was to
      investigate the hypothesis that maturational constraints may have different
      effects upon the development of the functional specializations of distinct sub
      within language. Subjects were 61 adult Chinese/English bilinguals who were
      exposed to English at different points in development: 1-3, 4-6, 7-10, 11-13, and
      after 16 years of age. Event-related brain potentials (ERPs) and behavioral
      responses were obtained as subjects read sentences that included semantic
      anomalies, three types of syntactic violations (phrase structure, specificity
      constraint, and subjacency constraint), and their controls. The accuracy in
      judging the grammaticality for the different types of syntactic rules and their
      associated ERPs was affected by delays in second language exposure as short as 1
      3 years. By comparison the N400 response and the judgment accuracies in detecting
      semantic anomalies were altered only in subjects who were exposed to English
      after 11-13 and 16 years of age, respectively. Further, the type of changes
      occurring in ERPs with delays in exposure were qualitatively different for
      semantic and syntactic processing. All groups displayed a significant N400 effect
      in response to semantic anomalies, however, the peak latencies of the N400
      elicited in bilinguals who were exposed to English between 11-13 and >16 years
      occurred later, suggesting a slight slowing in processing. For syntactic
      processing. the ERP differences associated with delays in exposure to English
      were observed in the morphology and distribution of components. Our findings are
      consistent with the view that maturational changes significantly constrain the
      development of the neural systems that are relevant for language and, further,
      that subsystems specialized for processing different aspects of language display
      different sensitive periods. 

PMID- 23968151
TI  - The hippocampus and cerebellum in adaptively timed learning, recognition, and
      movement.
AB  - The concepts of declarative memory and procedural memory have been used to
      distinguish two basic types of learning. A neural network model suggests how such
      memory processes work together as recognition learning, reinforcement learning,
      and sensorimotor learning take place during adaptive behaviors. To coordinate
      these processes, the hippocampal formation and cerebellum each contains circuits
      that learn to adaptively time their outputs. Within the model, hippocampal timing
      helps to maintain attention on motivationally salient goal objects during
      variable task-related delays, and cerebellar timing controls the release of
      conditioned responses. This property is part of the model's description of how
      cognitive-emotional interactions focus attention on motivationally valued cues,
      and how this process breaks down due to hippocampal ablation. The model suggests
      that the hippocampal mechanisms that help to rapidly draw attention to salient
      cues could prematurely release motor commands were not the release of these
      commands adaptively timed by the cerebellum. The model hippocampal system
      modulates cortical recognition learning without actually encoding the
      representational information that the cortex encodes. These properties avoid the
      difficulties faced by several models that propose a direct hippocampal role in
      recognition learning. Learning within the model hippocampal system controls
      adaptive timing and spatial orientation. Model properties hereby clarify how
      hippocampal ablations cause amnesic symptoms and difficulties with tasks which
      combine task delays, novelty detection, and attention toward goal objects amid
      distractions. When these model recognition, reinforcement, sensorimotor, and
      timing processes work together, they suggest how the brain can accomplish
      conditioning of multiple sensory events to delayed rewards, as during serial
      compound conditioning. 

PMID- 23968152
TI  - Monkey and human face perception: inversion effects for human faces but not for
      monkey faces or scenes.
AB  - Three rhesus monkeys and two groups of 10 human subjects judged upright or
      inverted pictures as same or different. The pictures were black and white pairs
      of human faces, monkey faces, or scenes. The monkeys were trained with sets of 50
      pictures and were tested with other sets of 36 pictures from each category. The
      groups of 10 human subjects were tested with the same pictures used to test
      monkeys. Both monkeys and humans showed large performance decrements to inverted
      human faces relative to upright human faces but neither species showed inversion
      effects for monkey faces or scenes. A second test with both monkeys and humans
      showed the same pattern of results with a different set of human-face pictures
      that varied more in sex (female as well as male), facial hair, eyeglasses,
      haircut, view angle, and background than those of the first test. The results
      indicate similar face-processing mechanisms in monkeys and humans despite
      experiential and evolutionary differences. 

PMID- 23968147
TI  - Transglutaminse 2 and EGGL, the protein cross-link formed by transglutaminse 2,
      as therapeutic targets for disabilities of old age.
AB  - Aging of the extracellular matrix (ECM), the protein matrix that surrounds and
      penetrates the tissues and binds the body together, contributes significantly to
      functional aging of tissues. ECM proteins become increasingly cross-linked with
      age, and this cross-linking is probably important in the decline of the ECM's
      function. This article reviews the role of epsilon-(gamma-glutamyl)-lysine
      (EGGL), a cross-link formed by transglutaminase enzymes, and particularly the
      widely expressed isozyme transglutaminase 2 (TG2), in the aging ECM. There is
      little direct data on EGGL accumulation with age, and no direct evidence of a
      role of EGGL in the aging of the ECM with pathology. However, several lines of
      circumstantial evidence suggest that EGGL accumulates with age, and its
      association with pathology suggests that this might reflect degradation of ECM
      function. TG activity increases with age in many circumstances. ECM protein
      turnover is such that some EGGL made by TG is likely to remain in place for
      years, if not decades, in healthy tissue, and both EGGL and TG levels are
      enhanced by age-related diseases. If further research shows EGGL does accumulate
      with age, removing it could be of therapeutic benefit. Also reviewed is the
      blockade of TG and active removal of EGGL as therapeutic strategies, with the
      conclusion that both have promise. EGGL removal may have benefit for acute
      fibrotic diseases, such as tendinopathy, and for treating generalized decline in
      ECM function with old age. Extracellular TG2 and EGGL are therefore therapeutic
      targets both for specific and more generalized diseases of aging.

PMID- 23968153
TI  - Semantic processing and orthographic specificity in hemispatial neglect.
AB  - Two sets of experiments, each consisting of a semantic priming task and a
      discrimination task, investigated the proceedings of lexical information in the
      neglected visual field. In the semantic priming task, subjects made lexical
      decisions to target words preceded by lateralized word primes; in the
      discrimination task, they indicated which of two words corresponded to a target
      word presented to the left visual field (LVF) or right visual field (RVF). The
      first set of experiments indicated that although patients were unable to
      discriminate words presented in the LVF, they showed significant priming when LVF
      primes were followed by semantically related targets compared to unrelated
      targets. The second set of experiments further examined the nature of this
      priming effect by comparing priming in a condition in which primes were
      semantically related to the target word (e.g., TEA-CUP) and a condition in which
      primes were unrelated to the target word, but orthographically similar to a
      related prime (e.g., PEA-CUP). This experiment replicated the previously
      established semantic priming effects and demonstrated significant negative
      priming for targets preceded by LVF primes that were orthographically similar to
      a semantically related word. Again, patients performed at chance in the forced
      choice discrimination task when targets were presented in the LVF These findings
      indicate that semantic processing of neglected lexical information is based on
      fully specified perceptual and orthographic information. A lateral inhibitory
      mechanism is proposed that maximizes the probability, albeit unsuccessfully, that
      neglected orthographic information will reach awareness. 

PMID- 23968155
TI  - Mindblindness.

PMID- 23968154
TI  - Preference of personal to extrapersonal space in a visuomotor task.
AB  - The speed of visually triggered movements depends, among other things, on the
      time needed for visuomotor transformations. We show that it takes on average 20
      40 msec less time to respond to visual stimuli when they are projected on the
      reacting fingers than a few centimeters away from them. The result implies
      significant preference of the personal space to the extrapersonal space for
      stimuli used in the initiation of visually triggered movements. 

PMID- 23968156
TI  - Improvement of carrier diffusion length in silicon nanowire arrays using atomic
      layer deposition.
AB  - To achieve a high-efficiency silicon nanowire (SiNW) solar cell, surface
      passivation technique is very important because a SiNW array has a large surface
      area. We successfully prepared by atomic layer deposition (ALD) high-quality
      aluminum oxide (Al2O3) film for passivation on the whole surface of the SiNW
      arrays. The minority carrier lifetime of the Al2O3-depositedSiNW arrays with bulk
      silicon substrate was improved to 27 MUs at the optimum annealing condition. To
      remove the effect of bulk silicon, the effective diffusion length of minority
      carriers in the SiNW array was estimated by simple equations and a device
      simulator. As a result, it was revealed that the effective diffusion length in
      the SiNW arrays increased from 3.25 to 13.5 MUm by depositing Al2O3 and post
      annealing at 400 degrees C. This improvement of the diffusion length is very
      important for application to solar cells, and Al2O3 deposited by ALD is a
      promising passivation material for a structure with high aspect ratio such as
      SiNW arrays. 

PMID- 23968157
TI  - CHF5074 reduces biomarkers of neuroinflammation in patients with mild cognitive
      impairment: a 12-week, double-blind, placebo-controlled study.
AB  - As neuroinflammation is an early event in the pathogenesis of Alzheimer' s
      disease, new selective antiinflammatory drugs could lead to promising preventive
      strategies. We evaluated the safety, tolerability, pharmacokinetics and
      pharmacodynamics of CHF5074, a new microglial modulator, in a 12-week, double
      blind, placebo-controlled, parallel groups, ascending dose study involving 96 MCI
      patients. Subjects were allocated into three successive study cohorts to receive
      ascending, titrated doses of CHF5074 (200, 400 or 600 mg/day) or placebo. Vital
      signs, cardiac safety, neuropsychological performance and safety clinical
      laboratory parameters were assessed on all subjects. Plasma samples were
      collected throughout the study for measuring drug concentrations, soluble CD40
      ligand (sCD40L) and TNF-alpha. At the end of treatment, cerebrospinal fluid (CSF)
      samples were optionally collected after the last dose to measure drug levels,
      beta- amyloid1-42 (Abeta42), tau, phospho-tau181, sCD40L and TNF-alpha. Ten
      patients did not complete the study: one in the placebo group (consent
      withdrawn), two in the 200-mg/day treatment group (consent withdrawn and unable
      to comply) and seven in the 400-mg/day treatment group (five AEs, one consent
      withdrawn and one unable to comply). The most frequent treatment-emergent adverse
      events were diarrhea, dizziness and back pain. There were no clinically
      significant treatmentrelated clinical laboratory, vital sign or ECG
      abnormalities. CHF5074 total body clearance depended by gender, age and
      glomerular filtration rate. CHF5074 CSF concentrations increased in a dose
      dependent manner. At the end of treatment, mean sCD40L and TNF-alpha levels in
      CSF were found to be inversely related to the CHF5074 dose (p=0.037 and p=0.001,
      respectively). Plasma levels of sCD40L in the 600-mg/day group were significantly
      lower than those measured in the placebo group (p=0.010). No significant
      differences between treatment groups were found in neuropsychological tests but a
      positive dose-response trend was found on executive function in APOE4 carriers.
      This study shows that CHF5074 is well tolerated in MCI patients after a 12-week
      titrated treatment up to 600 mg/day and dose-dependently affects central nervous
      system biomarkers of neuroinflammation. 

PMID- 23968158
TI  - Binding of chondroitin 4-sulfate to cathepsin S regulates its enzymatic activity.
AB  - Human cysteine cathepsin S (catS) participates in distinct physiological and
      pathophysiological cellular processes and is considered as a valuable therapeutic
      target in autoimmune diseases, cancer, atherosclerosis, and asthma. We evaluated
      the capacity of negatively charged glycosaminoglycans (heparin, heparan sulfate,
      chondroitin 4/6-sulfates, dermatan sulfate, and hyaluronic acid) to modulate the
      activity of catS. Chondroitin 4-sulfate (C4-S) impaired the collagenolytic
      activity (type IV collagen) and inhibited the peptidase activity (Z-Phe-Arg-AMC)
      of catS at pH 5.5, obeying a mixed-type mechanism (estimated Ki = 16.5 +/- 6
      MUM). Addition of NaCl restored catS activity, supporting the idea that
      electrostatic interactions are primarly involved. Furthermore, C4-S delayed in a
      dose-dependent manner the maturation of procatS at pH 4.0 by interfering with the
      intermolecular processing pathway. Binding of C4-S to catS was demonstrated by
      gel-filtration chromatography, and its affinity was measured by surface plasmon
      resonance (equilibrium dissociation constant Kd = 210 +/- 40 nM). Moreover, C4-S
      induced subtle conformational changes in mature catS as observed by intrinsic
      fluorescence spectroscopy analysis. Molecular docking predicted three specific
      binding sites on catS for C4-S that are different from those found in the crystal
      structure of the cathepsin K-C4-S complex. Overall, these results describe a
      novel glycosaminoglycan-mediated mechanism of catS inhibition and suggest that C4
      S may modulate the collagenase activity of catS in vivo. 

PMID- 23968159
TI  - Effect of lone-electron-pair cations on the orientation of crystallographic shear
      planes in anion-deficient perovskites.
AB  - Factors affecting the structure and orientation of the crystallographic shear
      (CS) planes in anion-deficient perovskites were investigated using the (Pb(1
      z)Sr(z))(1-x)Fe(1+x)O(3-y) perovskites as a model system. The isovalent
      substitution of Sr(2+) for Pb(2+) highlights the influence of the A cation
      electronic structure because these cations exhibit very close ionic radii. Two
      compositional ranges have been identified in the system: 0.05 <= z <= 0.2, where
      the CS plane orientation gradually varies but stays close to (203)p, and 0.3 <= z
      <= 0.45 with (101)p CS planes. The incommensurately modulated structure of
      Pb0.792Sr0.168Fe1.040O2.529 was refined from neutron powder diffraction data
      using the (3 + 1)D approach (space group X2/m(alpha0gamma), X = (1/2, 1/2, 1/2,
      1/2), a = 3.9512(1) A, b = 3.9483(1) A, c = 3.9165(1) A, beta = 93.268(2) degrees
      , q = 0.0879(1)a* + 0.1276(1)c*, RF = 0.023, RP = 0.029, and T = 900 K). A
      comparison of the compounds with different CS planes indicates that the
      orientation of the CS planes is governed mainly by the stereochemical activity of
      the lone-electron-pair cations inside the perovskite blocks.

PMID- 23968160
TI  - Menarche, puberty and psychiatric disorders.
AB  - OBJECTIVE: Puberty and adolescence are important periods about mental health,
      particularly for women. Relationship between age of menarche, psychiatric
      complaints during adolescence and family stories of psychiatric disorders are
      investigated. MATERIALS AND METHODS: The study is conducted with 61 patients with
      schizophrenia, 35 patients with bipolar affective disorder, 40 patients with
      depressive disorder and 60 healthy control subjects. All subjects were evaluated
      with SCID-I and questionnaire fit for the aim of the study was fulfilled.
      RESULTS: Bipolar affective disorder had a stronger relationship with menarche,
      psychiatric problems during adolescence were related with early onset of illness
      in schizophrenia and bipolar groups. Family story of psychiatric illness was
      related with psychological problems during puberty in schizophrenia group.
      CONCLUSION: This study underlies the puberty and adolescence period for
      psychiatric illness. An integrative clinical approach is suggested while
      examining the psychiatric illness at the basis of engaged roles of hormonal
      effects of menarche, social effect of puberty psychiatric complaints and
      genetical and psychosocial burden of family story of illness.

PMID- 23968161
TI  - The formation of surface multilayers at the air-water interface from sodium
      polyethylene glycol monoalkyl ether sulfate/AlCl(3) solutions: the role of the
      size of the polyethylene oxide group.
AB  - Neutron reflectivity, NR, and surface tension, ST, have been used to study the
      surface adsorption properties at the air-water interface of the anionic
      surfactant sodium polyethylene glycol monododecyl ether sulfate (sodium lauryl
      ether sulfate, SLES) in the presence of Al(3+) multivalent counterions, by the
      addition of AlCl3. In the absence of AlCl3 and at low AlCl3 concentrations
      monolayer adsorption is observed. With increasing AlCl3 concentration, surface
      multilayer formation is observed, driven by SLES/Al(3+) complex formation. The
      onset of multilayer formation occurs initially as a single bilayer or a
      multilayer structure with a limited number of bilayers, N, <=3, and ultimately at
      higher AlCl3 concentrations N is large, >20. The evolution in the surface
      structure is determined by the surfactant and AlCl3 concentrations, and the size
      of the polyethylene oxide group in the different SLES surfactants studied. From
      the NR data, approximate surface phase diagrams are constructed, and the
      evolution of the surface structure with surfactant and electrolyte concentration
      is shown to be dependent on the size of the polyethylene oxide group. As the
      polyethylene oxide group increases in size the multilayer formation requires
      increasingly higher surfactant and AlCl3 concentrations to promote the formation.
      This is attributed to the increased steric hindrance of the polyethylene oxide
      group disrupting SLES/Al(3+) complex formation. 

PMID- 23968162
TI  - Stereocontrolled cyanohydrin ether synthesis through chiral Bronsted acid
      mediated vinyl ether hydrocyanation.
AB  - Vinyl ethers can be protonated to generate oxocarbenium ions that react with
      Me3SiCN to form cyanohydrin alkyl ethers. Reactions that form racemic products
      proceed efficiently upon conversion of the vinyl ether to an alpha-chloro ether
      prior to cyanide addition in a pathway that proceeds through Bronsted acid
      mediated chloride ionization. Enantiomerically enriched products can be accessed
      by directly protonating the vinyl ether with a chiral Bronsted acid to form a
      chiral ion pair. Me3SiCN acts as the nucleophile and PhOH serves as a
      stoichiometric proton source in a rare example of asymmetric bimolecular
      nucleophilic addition into an oxocarbenium ion. Computational studies have
      provided a model for the interaction between the catalyst and the oxocarbenium
      ion. 

PMID- 23968163
TI  - Linking brain to behavior for the visual perception of figures and objects.
AB  - The dissociation of a figure from its background is an essential feat of visual
      perception, as it allows us to detect, recognize, and interact with shapes and
      objects in our environment. In order to understand how the human brain gives rise
      to the perception of figures, we here review experiments that explore the links
      between activity in visual cortex and performance of perceptual tasks related to
      figure perception. We organize our review according to a proposed model that
      attempts to contextualize figure processing within the more general framework of
      object processing in the brain. Overall, the current literature provides us with
      individual linking hypotheses as to cortical regions that are necessary for
      particular tasks related to figure perception. Attempts to reach a more complete
      understanding of how the brain instantiates figure and object perception,
      however, will have to consider the temporal interaction between the many regions
      involved, the details of which may vary widely across different tasks. 

PMID- 23968164
TI  - Blisters in a stem cell transplant patient.

PMID- 23968165
TI  - Robotic radiosurgery versus micro-multileaf collimator: a dosimetric comparison
      for large or critically located arteriovenous malformations.
AB  - BACKGROUND: Stereotactic irradiation of large or critically located arteriovenous
      malformations (AVMs) is a special challenge for clinicians and radiation
      physicists. To date, no comprehensive comparison of two linac-based radiosurgery
      systems used for hypofractionated radiotherapy of large AVMs was published. The
      aim of the study was to compare dose distributions between CyberKnife (CK) system
      and linac with a micro-multileaf collimator (L-mMLC) in high-grade or critically
      located cerebral AVMs. METHODS: Two sets of plans made for 15 different patients
      with at least 95% target coverage were selected for comparisons. Conformity (CI),
      homogeneity (HI) and gradient score (GSI) indices, conformity index proposed by
      Lomax (CIL), conformation number (CN), quality of coverage (Q), volumes of brain
      receiving 12,10,8,6,4, and 2 Gy, minimum and maximum doses for critical
      structures in both treatment planning systems (TPS) were compared. Finally, the
      number of monitor units needed to deliver the prescribed dose was compared.
      RESULTS: The mean minimum doses in the target volume were 93.3% (CK) and 90.7% (L
      mMLC),p=n.s, maximum: 119.7 and 110%, respectively (p=0.004). The mean CI was
      1.46 and 1.86, HI: 1.2, and 1.11, CIL 0.7, and 0.6, CN: 0.68 and 0.58 for CK and
      mMLC, respectively (p<0.05). The values of GSI and Q were not significantly
      different. The volumes of the brain receiving low doses (4 Gy and 2 Gy) were
      significantly lower in the CK system. The number of monitor units necessary to
      deliver the prescribed dose was significantly greater in case of the CK system.
      CONCLUSIONS: Better conformity can favor the CK system for treatment of large
      AVMs at the cost of higher maximum doses and worse homogeneity. L-mMLC is
      superior when shorter treatment time is required. Neither system can assure
      satisfying dose gradients outside large targets surrounded by numerous critical
      structures.

PMID- 23968166
TI  - Renal injury and Nrf2 modulation in mouse kidney following chronic exposure to
      TiO2 nanoparticles.
AB  - TiO2 nanoparticles (NPs) are used in the food industry but have potential toxic
      effects in humans and animals. TiO2 NPs impair renal function and cause oxidative
      stress and renal inflammation in mice, associated with inhibition of nuclear
      factor erythroid-2-related factor 2 (Nrf2), which regulates genes encoding many
      antioxidants and detoxifying enzymes. This study determined whether TiO2 NPs
      activated the Nrf2 signaling pathway. Mice exhibited accumulation of reactive
      oxygen species and peroxidation of lipid, protein, and DNA in the kidney, coupled
      with renal dysfunction, glutathione depletion, inflammatory cell infiltration,
      fatty degeneration, and apoptosis. These were associated with increased
      expression of NOX4, cyclooxygenase-2, and nuclear factor-kappaB. Oxidative stress
      and inflammation were accompanied by decreased expression of Nrf2 and down
      regulation of its target gene products including heme oxygenase 1, glutamate
      cysteine ligase catalytic subunit, and glutathione S-transferase. Chronic TiO2 NP
      exposure is associated with suppression of Nrf2, which contributes to the
      pathogenesis of oxidative stress and inflammation.

PMID- 23968167
TI  - An anti-Aspergillus protein from Escherichia coli DH5alpha: putative inhibitor of
      siderophore biosynthesis in Aspergillus fumigatus.
AB  - An antifungal protein designated as anti-Aspergillus protein (AAP), produced by
      Escherichia coli DH5alpha, was purified and characterised. It exhibited a
      molecular weight of 60 kDa on Sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis analysis and depicted 99% purity on ultra performance liquid
      chromatography. The purified protein manifested antimycotic potential against
      pathogenic isolates of Aspergillus spp., depicting a minimum inhibitory
      concentration in the range 15.62-31.25 MUg ml(-1) and 5.0-10.0 MUg per disc,
      using microbroth dilution, spore germination inhibition and disc diffusion assays
      respectively. In vitro toxicity tests demonstrated that it showed no toxicity
      against human erythrocytes at doses up to 1000 MUg ml(-1) . Matrix-assisted laser
      desorption ionisation-Time-of-flight analysis of trypsin-digested peptides of
      purified protein and subsequent Mascot search revealed that several peptides of
      AAP have identity with bacterial siderophore biosynthetic protein, i.e. non
      ribosomal peptide synthetase enzyme, involved in critical step of fungal
      siderophore biosynthesis. Siderophore-based inhibition was further corroborated
      by Chrome azurol S assay. Hence, the antagonistic effect might be the result of
      impediment in siderophore-mediated iron uptake and transport process which may
      cause critical consequences on Aspergillus growth and virulence. 

PMID- 23968168
TI  - Credibility and treatment fidelity may matter in twelve-step treatment.

PMID- 23968169
TI  - Are "extreme consumption games" drinking games? Sometimes it's a matter of
      perspective.
AB  - Drinking games are widespread on college campuses and pose health risks to their
      players. Although there has been considerable research progress in the college
      drinking games literature, there does not appear to be a standard definition of
      the term "drinking games." Researchers, however, have attempted to classify and
      categorize drinking games in a systematic manner. For example, one category of
      drinking games (e.g., chugging, keg stands) is often referred to as consumption
      or extreme consumption games. Questions remain as to whether or how these types
      of games align with researchers' definitions of drinking games or the
      categorization systems advanced by researchers in the field. Potential challenges
      regarding the definition and categorization of drinking games, particularly with
      respect to extreme consumption types of games, are discussed.

PMID- 23968170
TI  - Multiple fruit-flavored alcoholic drinks in a can (MFAC): an overlooked class of
      potentially harmful alcohol products.
AB  - This article examines an overlooked class of alcohol products, described herein
      as multiple fruit-flavored alcoholic drinks in a can (MFAC). The article
      describes how characteristics of these products likely contribute to hazardous
      alcohol consumption among youth. Government regulation of these products may be
      needed to protect adolescent and young adult populations. National substance
      abuse surveillance systems should consider immediate adoption of MFAC use
      indicators to determine use and harm associated with these products, and to
      assess the effectiveness of future regulatory actions.

PMID- 23968171
TI  - The advent of a new pseudoephedrine product to combat methamphetamine abuse.
AB  - BACKGROUND: The personal and societal effects of methamphetamine abuse are well
      documented. The ease of accessibility to methamphetamine and the quality of the
      "high" it produces makes the drug highly desired by its abusers. Over time, many
      methamphetamine users will also become methamphetamine cooks, where
      pseudoephedrine in over-the-counter cold products is converted to methamphetamine
      through a simple, albeit extremely dangerous, process. New laws limiting access
      to these products have had limited success. No existing commercial
      pseudoephedrine products offer significant impediments to slow or limit the
      extraction and conversion of pseudoephedrine in clandestine methamphetamine
      laboratories. OBJECTIVE AND METHODS: A new pseudoephedrine 30 mg tablet product
      using Impede technology (Nexafed(r)) to deter methamphetamine production has
      recently been introduced into the marketplace. Using methods designed to mimic
      clandestine laboratory processes, the ability of this product to disrupt
      extraction and conversion of pseudoephedrine to methamphetamine yet provide
      therapeutic effectiveness was evaluated. RESULTS: ImpedeTM technology tablets
      limited the extraction and/or conversion of pseudoephedrine to methamphetamine
      when compared to a commercially marketed pseudoephedrine product (Sudafed(r)).
      Nexafed(r) tablets were also shown to be bioequivalent to the same control
      product, thus ensuring therapeutic equivalence. CONCLUSIONS: With the advent of
      new pseudoephedrine products in the marketplace with features to limit the
      extraction and conversion of pseudoephedrine to methamphetamine, new tools are
      now available to minimize the clandestine manufacture of the drug and potentially
      limit its social impact.

PMID- 23968172
TI  - A proposal to evaluate mechanistic efficacy of hallucinogens in addiction
      treatment.
AB  - Current treatments for addiction are frequently ineffective. Hallucinogenic
      therapy has been indicated as helpful for a range of substance use disorders, yet
      this approach remains understudied and publicly unavailable. It is nonetheless a
      promising treatment, which has significant, long-term beneficial effects with
      single doses and a profile characterized by general safety, low toxicity, and non
      addictiveness. However, pharmacological interventions, such as hallucinogens,
      should not be offered if the same effects (e.g. psychological insights/mystical
      experiences) and outcomes (e.g. decreased drug use) could be achieved absent
      pharmacological intervention. To date, there have been no clinical comparisons of
      drug-induced altered states with non-drug-induced states for addiction treatment.
      We propose and then outline a clinical trial to address this gap in knowledge.
      The proposed design would evaluate abstinence outcomes in a population of
      prescription opioid abusers after exposure to one of three conditions: a drug
      induced altered state using psilocybin, a non-drug-induced altered state via
      hyperventilation (Holotropic Breathwork), and an active placebo with niacin. The
      outcomes of such a study would reveal important differences in therapeutic
      potential by discriminating hallucinogen-dependent effects from those
      psychological effects resulting from altered states.

PMID- 23968173
TI  - Gender disparity in utilization rates of substance abuse services among female ex
      offenders: a population-based analysis.
AB  - BACKGROUND: The use and abuse of substances is common among offender populations.
      Although the female former offender population has risen substantially in recent
      decades, relatively little is known about their substance abuse treatment
      experiences. OBJECTIVE: This study examines disparities in substance abuse
      treatment utilization among the US population with special focus upon formerly
      incarcerated female offenders. METHODS: Using data from the National
      Epidemiologic Survey on Alcohol and Related Conditions (NESARC, n = 43,093)
      collected in 2001-2002 and 2004-2005 the authors compared lifetime rates of
      substance abuse treatment utilization between female and male ex-offenders with
      the U.S. general population. The sample population covered inpatient and
      community based substance use treatment, detoxification and rehabilitation
      programs. It is a nationally representative sample of noninstitutionalized
      persons over the age of 18. Multinomial logistic regression was performed and
      likelihood of using substance use treatment and services was calculated using
      adjusted odds ratios (AOR). RESULTS: Compared to male ex-offenders, female ex
      offenders were 52% less likely to use substance-abuse treatment services (AOR =
      0.48, 95% CI = 0.26-0.89) and 51% less likely to use rehabilitation programs (AOR
      = 0.49, 95% CI = 0.26-0.93). Compared to females in the general population,
      female ex-offenders were 10 times more likely to use substance-abuse treatment
      services (AOR = 10.14, 95% CI = 5.71-18.00), 10.5 times more likely to use
      substance detoxification programs (AOR = 10. 45, 95% CI = 5.64-19.39); 8 times
      more likely to use inpatient wards (AOR = 8.05, 95% CI = 4.16-15.59); 9 times
      more likely to use outpatient wards (AOR = 9.06, 95% CI = 4.89-16.81), and 12
      times more likely to use substance-abuse rehabilitation programs (AOR = 12.06,
      95% CI = 6.55-22.22). CONCLUSIONS: While female ex-offenders were more likely to
      have used a range of substance abuse services when compared to the general
      population, they were less likely to use substance-abuse treatment services and
      rehabilitation programs than male ex-offenders.

PMID- 23968176
TI  - Time-motion analysis of basketball players: a reliability assessment of Video
      Manual Motion Tracker 1.0 software.
AB  - This study assessed the measurement error of a monitoring system, the Video
      Manual Motion Tracker 1.0 (VMMT1.0), during time-motion analysis of basketball
      players. In this study, four reliability parameters were used to assess the
      measurement error of the system: the systematic bias, the inter-observer
      reliability, the intra-observer reliability and the absolute reliability. A
      basketball game video was used for the analysis. To assess the inter-observer
      reliability, two observers analysed a player's covered distance for 50 different
      periods of the game. To assess the relative and absolute reliability of the
      covered distance, the chosen players were monitored three times by 41 qualified
      observers. The findings did not indicate a significant systematic bias in the
      measurement error using the VMMT1.0 (one-way ANOVA, P > 0.05). The intra-observer
      reliability of the monitoring system was rated as very high (intraclass
      correlation, ICC = 0.999), similar to its inter-observer reliability (Pearson
      product-moment correlation, r = 0.994). The absolute reliability does not appear
      to be significant (standard error of measurement, SEM = 0.34 m). The results
      showed that the measurement error of the VMMT1.0 is acceptable and comparable
      with that of other time-motion analysis techniques.

PMID- 23968174
TI  - MethyQA: a pipeline for bisulfite-treated methylation sequencing quality
      assessment.
AB  - BACKGROUND: DNA methylation is an epigenetic event that adds a methyl-group to
      the 5' cytosine. This epigenetic modification can significantly affect gene
      expression in both normal and diseased cells. Hence, it is important to study
      methylation signals at the single cytosine site level, which is now possible
      utilizing bisulfite conversion technique (i.e., converting unmethylated Cs to Us
      and then to Ts after PCR amplification) and next generation sequencing (NGS)
      technologies. Despite the advances of NGS technologies, certain quality issues
      remain. Some of the more prevalent quality issues involve low per-base sequencing
      quality at the 3' end, PCR amplification bias, and bisulfite conversion rates.
      Therefore, it is important to conduct quality assessment before downstream
      analysis. To the best of our knowledge, no existing software packages can
      generally assess the quality of methylation sequencing data generated based on
      different bisulfite-treated protocols. RESULTS: To conduct the quality assessment
      of bisulfite methylation sequencing data, we have developed a pipeline named
      MethyQA. MethyQA combines currently available open-source software packages with
      our own custom programs written in Perl and R. The pipeline can provide quality
      assessment results for tens of millions of reads in under an hour. The novelty of
      our pipeline lies in its examination of bisulfite conversion rates and of the DNA
      sequence structure of regions that have different conversion rates or coverage.
      CONCLUSIONS: MethyQA is a new software package that provides users with a unique
      insight into the methylation sequencing data they are researching. It allows the
      users to determine the quality of their data and better prepares them to address
      the research questions that lie ahead. Due to the speed and efficiency at which
      MethyQA operates, it will become an important tool for studies dealing with
      bisulfite methylation sequencing data.

PMID- 23968175
TI  - Detection of comorbidities and synchronous primary tumours via thoracic
      radiography and abdominal ultrasonography and their influence on treatment
      outcome in dogs with soft tissue sarcomas, primary brain tumours and intranasal
      tumours.
AB  - Canine soft tissue sarcomas (STS), primary brain tumours and intranasal tumours
      are commonly treated with radiotherapy (RT). Given the low metastatic potential
      of these tumours, recommendations regarding imaging tests as staging are variable
      among institutions. The purpose of our study was to describe thoracic
      radiographic and abdominal ultrasonographic findings in dogs with these neoplasms
      and to investigate association of abnormal findings with alterations in
      recommended treatment. Medical records from 101 dogs, each having thoracic
      radiographs and abdominal ultrasound performed as part of their staging, were
      reviewed. In 98 of 101 (97%), imaging abnormalities were detected, 27% of which
      were further investigated with fine needle aspiration cytology or biopsy. Nine
      percent of the detected abnormalities were considered serious comorbidities that
      altered treatment recommendations, including 3 (3%) which were confirmed as
      synchronous primary neoplasms. These findings may influence recommendations
      regarding the decision to perform thoracic radiographs and abdominal ultrasound
      prior to initiation of RT. 

PMID- 23968177
TI  - Imaging Cognition: An Empirical Review of PET Studies with Normal Subjects.
AB  - We review PET studies of higher-order cognitive processes, including attention
      (sustained and selective), perception (of objects, faces, and locations),
      language (word listening, reading, and production), working memory (phonological
      and visuo-spatial), semantic memory retrieval (intentional and incidental),
      episodic memory retrieval (verbal and nonverbal), priming, and procedural memory
      (conditioning and skill learning). For each process, we identify activation
      patterns including the most consistently involved regions. These regions
      constitute important components of the network of brain regions that underlie
      each function. 

PMID- 23968178
TI  - Spontaneous eye movements during visual imagery reflect the content of the visual
      scene.
AB  - In nine naive subjects eye movements were recorded while subjects viewed and
      visualized four irregularly-checkered diagrams. Scanpaths, defined as repetitive
      sequences of fixations and saccades were found during visual imagery and viewing.
      Positions of fixations were distributed according to the spatial arrangement of
      subfeatures in the diagrams. For a particular imagined diagrammatic picture, eye
      movements were closely correlated with the eye movements recorded while viewing
      the same picture. Thus eye movements during imagery are not random but reflect
      the content of the visualized scene. The question is discussed whether scanpath
      eye movements play a significant functional role in the process of visual
      imagery. 

PMID- 23968179
TI  - Spoken Sentence Comprehension in Aphasia: Event-related Potential Evidence for a
      Lexical Integration Deficit.
AB  - In this study the N400 component of the event-related potential was used to
      investigate spoken sentence understanding in Broca's and Wernicke's aphasics. The
      aim of the study was to determine whether spoken sentence comprehension problems
      in these patients might result from a deficit in the on-line integration of
      lexical information. Subjects listened to sentences spoken at a normal rate. In
      half of these sentences, the meaning of the final word of the sentence matched
      the semantic specifications of the preceding sentence context. In the other half
      of the sentences, the sentence-final word was anomalous with respect to the
      preceding sentence context. The N400 was measured to the sentence-final words in
      both conditions. The results for the aphasic patients (n = 14) were analyzed
      according to the severity of their comprehension deficit and compared to a group
      of 12 neurologically unimpaired age-matched controls, as well as a group of 6
      nonaphasic patients with a lesion in the right hemisphere. The nonaphasic brain
      damaged patients and the aphasic patients with a light comprehension deficit
      (high comprehenders, n = 7) showed an N400 effect that was comparable to that of
      the neurologically unimpaired subjects. In the aphasic patients with a moderate
      to severe comprehension deficit (low comprehenders, n = 7), a reduction and delay
      of the N400 effect was obtained. In addition, the P300 component was measured in
      a classical oddball paradigm, in which subjects were asked to count infrequent
      low tones in a random series of high and low tones. No correlation was found
      between the occurrence of N400 and P300 effects, indicating that changes in the
      N400 results were related to the patients' language deficit. Overall, the pattern
      of results was compatible with the idea that aphasic patients with moderate to
      severe comprehension problems are impaired in the integration of lexical
      information into a higher order representation of the preceding sentence context.

PMID- 23968180
TI  - Eye movements and orienting of attention in patients with visual neglect.
AB  - The aim of the present study was to assess the relationship between overt and
      covert orienting of attention in visual neglect patients with parietal and fronto
      parietal lesions. Two stimuli were presented at eccentricities of 8 degrees  or
      20 degrees  to the left (LVF) or right (RVF) visual fields and the patient was
      required to maintain fixation on the central mark and to respond only manually
      upon the appearance of the stimulus. Neglect patients with fronto-parietal lesion
      showed a lack of oculomotor control and the presence of leftward eye movements
      without corresponding attentional shifts. Neglect patients with parietal lesions
      did not show this phenomenon. They rarely responded ocularly and manually to LVF
      stimuli, whereas they were unable to inhibit an automatic ocular orienting
      reaction towards RVF stimuli. When a RVF stimuli triggered both ocular and
      attentional shifts, the pattern of responses revealed a retinal eccentricity
      effect. Patients were more accurate to respond to stimuli located at 8 degrees 
      than 20 degrees . In contrast, when a RVF stimuli triggered only attentional
      shifts, the results showed the attentional gradient effect (Iiidavas, 1990).
      Patients were more accu- rate to respond to stimuli located at 20 degrees  than 8
      degrees . Therefore, the results of the present study seem to suggest a
      functional dissociation of the mechanisms subserving attentional and gaze
      orienting and a differential role played by the frontal and parietal lobes in
      overt visual orienting. 

PMID- 23968181
TI  - Distributed cortical network for visual attention.
AB  - The contribution of prefrontal and posterior association cortex to voluntary and
      involuntary visual attention was as sessed using electrophysiological techniques
      in patients with focal lesions in prefrontal (n = 11), temporal-parietal (n =
      10), or lateral parietal cortex (n = 7). Subjects participated in a task
      requiring detection of designated target stimuli embedded in trains of repetitive
      stimuli. Infrequent and irrelevant novel visual stimuli were randomly
      interspersed with the target and background stimuli. Controls generated attention
      dependent N1 (170 msec) and N2 (243 msec) potentials maximal over extrastriate
      cortex. Anterior and posterior association cortex lesions reduced the amplitude
      of both the N1 and N2 potentials recorded over extrastriate cortex of the
      lesioned hemisphere. The pattern of results obtained reveals that an
      intrahemispheric network involving prefrontal and posterior association cortex
      modulates early visual processing in extrastriate regions. Voluntary target
      detection generated a parietal maximal P300 response (P3b) and irrelevant novel
      stimuli generated a more frontocentrally distributed P300 (P3a). Cortical lesions
      had differential effects on P3a and P3b potentials. The P3b was not significantly
      reduced in any cortical lesioned group. Conversely, the P3a was reduced by both
      prefrontal and posterior lesions with decrements most severe throughout the
      lesioned hemisphere. These data provide evidence that an association cortex
      network involving prefrontal and posterior regions is activated during
      orientation to novel events. The lack of a significant effect on the visual
      target P3b in patients with novelty P3a reductions supports the notion that
      different neural systems are engaged during voluntary vs involuntary atten- tion
      to visual stimuli. 

PMID- 23968182
TI  - Hemispheric organization of visual memories.
AB  - This study investigates the hemispheric organization of visual memories. In five
      experiments, we examine the processes associated with the recognition of line
      patterns that are flashed laterally during a study phase. The first three
      experiments demonstrate a recognition advantage for patterns presented at test in
      the same (rather than in the opposite) hemifield in which they were presented
      during a previous study phase. This difference was obtained even when stimuli
      were presented in different locations within the same hemifield. Experiment shows
      that patterns presented centrally during the recognition phase elicit ERPs that
      are systematically more negative over the hemisphere contralateral to the side at
      which they were presented during the study phase. In Experiment 5, however, we
      found that subjects were unable to indicate the side of initial presentation of
      the patterns. The results suggest that the memory traces left by laterally
      presented stimuli are more easily accessible in the contralateral hemisphere,
      which suggests a contralateral organization of visual memories. 

PMID- 23968183
TI  - Implicit and explicit conceptual memory following frontal lobe damage.
AB  - In two experiments, the performance of patients with frontal lobe lesions was
      examined on implicit and explicit tests of conceptual memory for organized lists
      of words. Frontal patients exhibited normal levels of conceptual priming on
      implicit category production and free association tests, but they exhibited
      impaired memory performance on explicit category- and associate-cued recall
      tests. The findings of normal performance on implicit conceptual tests suggest
      that frontal patients do not have a basic deficit in semantic processing of
      individual items. Impaired performance on explicit cued recall tests may be
      related to deficits in the use of organizational encoding and strategic retrieval
      processes. 

PMID- 23968184
TI  - Cortical synchronization and perceptual framing.
AB  - How does the brain group together different parts of an object into a coherent
      visual object representation? Different parts of an object may be processed by
      the brain at different rates and may thus become desynchronized. Perceptual
      framing is a process that resynchronizes cortical activities corresponding to the
      same retinal object. A neural network model is presented that is able to rapidly
      resynchronize desynchronized neural activities. The model provides a link between
      perceptual and brain data. Model properties quantitatively simulate perceptual
      framing data, including psychophysical data about temporal order judgments and
      the reduction of threshold contrast as a function of stimulus length. Such a
      model has earlier been used to explain data about illusory contour formation,
      texture segregation, shape-from-shading, 3-D vision, and cortical receptive
      fields. The model hereby shows how many data may be understood as manifestations
      of a cortical grouping process that can rapidly resynchronize image parts that
      belong together in visual object representations. The model exhibits better
      synchronization in the presence of noise than without noise, a type of stochastic
      resonance, and synchronizes robustly when cells that represent different stimulus
      orientations compete. These properties arise when fast long-range cooperation and
      slow short-range competition interact via nonlinear feedback interactions with
      cells that obey shunting equations. 

PMID- 23968185
TI  - A locus in human extrastriate cortex for visual shape analysis.
AB  - Positron emission tomography (PET) was used to locate an area in human
      extrastriate cortex that subserves a specific component process of visual object
      recognition. Regional blood flow increased in a bilateral extrastriate area on
      the inferolateral surface of the brain near the border between the occipital and
      temporal lobes (and a smaller area in the right fusiform gyms) when subjects
      viewed line drawings of 3-dimensional objects compared to viewing scrambled
      drawings with no clear shape interpretation. Responses were Seen for both novel
      and familiar objects, implicating this area in the bottom-up (i.e., memory
      independent) analysis of visual shape. 

PMID- 23968186
TI  - Memory encoding following complete callosotomy.
AB  - Three patients with complete resection of the corpus callosum were tested in a
      series of memory tasks to determine the effects of callosotomy on the encoding
      and retrieval of information in memory. Verbal and pictorial conjunction tests
      were administered to measure patients' ability to consolidate the elements of a
      stimulus into an accurate composite memory. Patients were also tested in a paired
      associate learning task to determine the consequences of callosotomy on the
      encoding and retrieval of associations between stimuli. Although callosotomy
      patients were unimpaired in the verbal conjunction task, results from both the
      pictorial conjunction task and the paired-associate learning task suggest that
      the absence of callosal cross-talk impairs encoding in these patients. In
      addition, the pattern of results in the paired-associate learning task suggests
      that callosotomy impairs retrieval processes. The role of the callosum in the
      formation of memory traces for nonverbal material and associations between verbal
      stimuli is discussed. 

PMID- 23968187
TI  - On knowing the auxiliary of a verb that cannot be named: evidence for the
      independence of grammatical and phonological aspects of lexical knowledge.
AB  - We report the case of an Italian anomic subject who was invariably able to
      provide the auxiliary of verbs he failed to produce in oral naming tasks. This
      pattern of performance contrasts with that of another Italian-speaking patient
      documented by Miceli and Caramazza (1988) who showed a selective impairment in
      accessing syntactic features of words, but not their phonological forms. This
      double dissociation suggests that syntactic and phonological information in the
      lexicon are accessed independently and represented in distinct neural structures.

PMID- 23968188
TI  - Research strategies for functional neuroimaging: a comment on the interview with
      R.g. Shulman.

PMID- 23968189
TI  - To the editor.

PMID- 23968190
TI  - Immunohistochemical analysis of FOXP3+ regulatory T cells in healthy human skin
      and autoimmune dermatoses.
AB  - BACKGROUND: Regulatory T cells (Tregs) play an important role in autoimmune
      diseases. In skin, the presence of Tregs is thought to be mandatory for
      suppression of autoreactive T cells. Here, we assess the number of Tregs in skin
      of healthy subjects and patients with an autoimmune dermatosis. METHODS:
      Immunohistochemical stainings for CD3 and FOXP3 on skin biopsies of healthy
      subjects and subjects with psoriasis, vitiligo, pemphigus vulgaris, bullous
      pemphigoid, and halo nevus to assess the number of T and regulatory T cells,
      respectively. RESULTS: Low numbers of CD3+ and FOXP3+ cells were seen in the skin
      of healthy controls (median = 0.5%). A significantly higher frequency of Tregs
      was seen in lesional skin of patients with psoriasis (median = 12.4%) and
      patients with bullous pemphigoid (median = 10.1%) as compared to controls. In
      vitiligo (median = 0.0%), pemphigus vulgaris (median = 5.2%), and halo nevi
      (median = 5.4%), no significant difference in number of FOXP3+ cells was observed
      when compared to controls. CONCLUSIONS: As confirmed in the literature, few Tregs
      were seen in healthy skin. A high number of Tregs were present in lesional skin
      from patients with psoriasis and bullous pemphigoid. These results support the
      hypothesis that not a decrease in number but rather a decrease in function of
      Tregs would be at the basis of autoimmune skin diseases, which could result in
      unrestrained activation autoreactive T cells in skin of patients with autoimmune
      dermatoses.

PMID- 23968191
TI  - Correlation of adrenomedullin gene expression in peripheral blood leukocytes with
      severity of ischemic stroke.
AB  - Human adrenomedullin (ADM), a 52-amino acid peptide, belongs to the
      calcitonin/calcitonin gene-related peptide (CGRP)/amylin peptide family. ADM acts
      as a multifunctional regulatory peptide and is upregulated in response to
      hypoxia. Previous microarray studies have found increased ADM gene (ADM)
      expression in peripheral blood cells of patients with stroke, however, it is
      unknown if an increased ADM level is correlated with severity of human ischemic
      stroke. This study investigated ADM expression in peripheral blood leukocytes
      (PBL) of healthy controls and subjects at day 1, week 1 and week 3 postacute
      ischemic stroke using rtPCR methodology. We found that ADM expression was
      significantly upregulated on the first day of stroke compared to the healthy
      subjects and the disease controls; the levels remained elevated for up to week 3.
      Further, ADM expression at day 1 was correlated with stroke severity measured by
      the National Institute of Healthy Stroke Scale (NIHSS), the modified Barthel
      Index (mBI) and the modified Rankin Scale (mRS). This could indicate that ADM
      expression level is related to the severity of tissue damage. We suggest that
      increased ADM expression in PBL after acute ischemic stroke is most likely to
      indicate that these cells have been subjected to hypoxia and that the magnitude
      of expression is likely to be related to the volume of hypoxic tissue. Hypoxia
      can affect lymphocytes function and could affect the immune response to stroke.
      The correlation of ADM expression level with the measures of stroke severity
      implicates ADM--a potential blood bio-marker in studies of ischemic stroke.

PMID- 23968192
TI  - Alcohol consumption, smoking and overweight as a burden for health care services
      utilization: a cross-sectional study in Estonia.
AB  - BACKGROUND: Alcohol consumption, smoking and weight problems are common risk
      factors for different health problems. We examine how these risk factors are
      associated with the use of health care services. METHODS: Data for 6500
      individuals in the 25-64 age group came from three cross-sectional postal surveys
      conducted in 2004, 2006, and 2008 in Estonia. The effect of alcohol consumption,
      smoking and weight problems on the use of primary and specialist care services,
      hospitalizations and ambulance calls was analysed separately for men and women by
      using binary logistic regression. RESULTS: Overweight and/or obesity were
      strongly related to the use of primary care and out-patient specialist services
      for both genders, and to hospitalizations and ambulance calls for women. Current
      smoking was related to ambulance calls for both genders, whereas smoking in the
      past was related to the use of primary care and specialist services among men and
      to hospitalizations among women. Beer drinking was negatively associated with all
      types of health care services and similar association was found between wine
      drinking and hospitalizations. Wine drinking was positively related to specialist
      visits. The frequent drinking of strong alcohol led to an increased risk for
      ambulance calls. Drinking light alcoholic drinks was positively associated with
      all types of health care services (except ambulance calls) among men and with the
      use of specialist services among women. CONCLUSIONS: Overweight and smoking had
      the largest impact on health care utilization in Estonia. Considering the high
      prevalence of these behavioural risk factors, health policies should prioritize
      preventive programs that promote healthy lifestyles in order to decrease the
      disease burden and to reduce health care costs.

PMID- 23968194
TI  - Magnetic nanoparticle heating and heat transfer on a microscale: Basic
      principles, realities and physical limitations of hyperthermia for tumour
      therapy.
AB  - In this review article we present basic principles of magnetically induced heat
      generation of magnetic nanoparticles for application in magnetic particle
      hyperthermia. After explanation of heating mechanisms, the role of particle
      particle as well as particle-tissue interactions is discussed with respect to
      achievable heating power of the particles inside the tumour. On the basis of heat
      transfer theory at the micro-scale, the balance between generated and dissipated
      heat inside the tumour and the resulting damaging effects for biological tissue
      is examined. The heating behaviour as a function of tumour size is examined in
      combination with feasible field strength and frequency. Numerical calculations
      and experimental investigations are used to show the lower tumour size limit for
      tumour heating to therapeutically suitable temperatures. In summary, this article
      illuminates practical aspects, limitations, and the state of the art for the
      application of magnetic heating in magnetic particle hyperthermia as thermal
      treatment of small tumours.

PMID- 23968193
TI  - Two-dimensional patterns of poly(N-isopropylacrylamide) microgels to spatially
      control fibroblast adhesion and temperature-responsive detachment.
AB  - Thermoresponsive poly(N-isopropyl acrylamide) (PNIPAM) microgels were patterned
      on polystyrene substrates via dip coating, creating cytocompatible substrates
      that provided spatial control over cell adhesion. This simple dip-coating method,
      which exploits variable substrate withdrawal speeds forming particle suspension
      stripes of densely packed PNIPAM microgels, while spacings between the stripes
      contained sparsely distributed PNIPAM microgels. The assembly of three different
      PNIPAM microgel patterns, namely, patterns composed of 50 MUm stripe/50 MUm
      spacing, 50 MUm stripe/100 MUm spacing, and 100 MUm stripe/100 MUm spacing, was
      verified using high-resolution optical micrographs and ImageJ analysis. PNIPAM
      microgels existed as monolayers within stripes and spacings, as revealed by
      atomic force microscopy (AFM). Upon cell seeding on PNIPAM micropatterned
      substrates, NIH3T3 fibroblast cells preferentially adhered within spacings to
      form cell patterns. Three days after cell seeding, cells proliferated to form
      confluent cell layers. The thermoresponsiveness of the underlying PNIPAM
      microgels was then utilized to recover fibroblast cell sheets from substrates
      simply by lowering the temperature without disrupting the underlying PNIPAM
      microgel patterns. Harvested cell sheets similar to these have been used for
      multiple tissue engineering applications. Also, this simple, low-cost, template
      free dip-coating technique can be utilized to micropattern multifunctional PNIPAM
      microgels, generating complex stimuli-responsive substrates to study cell
      material interactions and allow drug delivery to cells in a spatially and
      temporally controlled manner. 

PMID- 23968196
TI  - Actinic prurigo: a case-control study of risk factors.
AB  - BACKGROUND: Actinic prurigo (AP) is an idiopathic photodermatosis that usually
      onsets during childhood and predominates in women. It is characterized by the
      symmetrical involvement of sun-exposed areas of the skin, lips, and conjunctiva.
      OBJECTIVES: This study aimed to analyze the risk factors associated with AP using
      a case-control design. METHODS: All patients diagnosed with AP during 1990-2006
      at Dr. Manuel Gea Gonzalez General Hospital in Mexico City were included.
      Respective controls were recruited. Race, demographic, geographic, socioeconomic,
      environmental, clinical, and nutritional risk factors were assessed. RESULTS: A
      total of 132 persons were enrolled. These included 44 cases and two control
      groups comprising, respectively, dermatology and non-dermatology outpatients
      without AP or any autoimmune disease. Distribution by gender, age, place of
      birth, place of residence, and economic status did not differ significantly among
      the three groups. A total of 256 variables were analyzed. Only 19 variables were
      found to be statistically significant (P < 0.05). These were: use of a boiler;
      use of firewood; car ownership; use of earthenware; mixed material housing;
      socioeconomic level 1; sun exposure; use of soap; lemon consumption; use of
      moisturizing hair cream; living with pets in the house; living with farm animals;
      age; having a family member with AP; having had surgery; having had trauma;
      having been hospitalized; use of oral medication; and use of herbal medication.
      Of 40 macro- and micronutrients analyzed, 11 were found to have statistically
      significant effects (P < 0.05). CONCLUSIONS: Multiple epidemiologic, geographic,
      clinical, and immunologic factors are involved in the etiology of AP. This study
      proposes a clear line for research directed at specific risk factors that refer
      to an individual's clinical, allergic, health, and socioeconomic status. Further
      study should also investigate the etiologic role of diet in AP and the molecular
      mechanisms behind the development of AP to establish whether AP is caused by
      exposure to polycyclic aromatic hydrocarbons.

PMID- 23968195
TI  - Luminescence of [Ru(bpy)2(dppz)]2+ bound to RNA mismatches.
AB  - The luminescence of rac-[Ru(bpy)2(dppz)](2+) (bpy = 2,2'-bipyridine and dppz =
      dipyrido[3,2-a:2',3'-c]phenazine) was explored in the presence of RNA
      oligonucleotides containing a single RNA mismatch (CA and GG) in order to develop
      a probe for RNA mismatches. While there is minimal luminescence of
      [Ru(bpy)2(dppz)](2+) in the presence of matched RNA due to weak binding, the
      luminescence is significantly enhanced in the presence of a single CA mismatch.
      The luminescence differential between CA mismatched and matched RNA is
      substantially higher compared to the DNA analogue, and therefore,
      [Ru(bpy)2(dppz)](2+) appears to be also a sensitive light switch probe for a CA
      mismatch in duplex RNA. Although the luminescence intensity is lower in the
      presence of RNA than DNA, Forster resonance energy transfer (FRET) between the
      donor ruthenium complex and FRET acceptor SYTO 61 is successfully exploited to
      amplify the luminescence in the presence of the mismatch. Luminescence and
      quenching studies with sodium iodide suggest that [Ru(bpy)2(dppz)](2+) binds to
      these mismatches via metalloinsertion from the minor groove. This work provides
      further evidence that metalloinsertion is a general binding mode of octahedral
      metal complexes to thermodynamically destabilized mismatches not only in DNA but
      also in RNA. 

PMID- 23968197
TI  - 3,4-Dichlorophenoxyacetate interleaved into anionic clay for controlled release
      formulation of a new environmentally friendly agrochemical.
AB  - A new layered organic-inorganic nanohybrid material, zinc-aluminum-3,4
      dicholorophenoxyacetate (N3,4-D) in which an agrochemical, 3,4
      dichlorophenoxyacetic acid (3,4-D), is intercalated into zinc-aluminum-layered
      double hydroxide (ZAL), was synthesized by coprecipitation method. A well-ordered
      nanomaterial was formed with a percentage loading of 53.5% (w/w). Due to the
      inclusion of 3,4-D, basal spacing expanded from 8.9 A in ZAL to 18.7 A in N3,4-D.
      The Fourier transform infrared study shows that the absorption bands of the
      resulting nanohybrid composed of both the 3,4-D and ZAL further confirmed the
      intercalation episode. Thermal analysis shows that ZAL host enhances the thermal
      stability of 3,4-D. Controlled-release experiment shows that the release of 3,4-D
      in the aqueous media is in the order of phosphate > carbonate > sulfate >
      chloride. These studies demonstrate the successful intercalation of the 3,4-D and
      its controlled release property in various aqueous media. 

PMID- 23968198
TI  - Effects of different protocols of hydration on cardiorespiratory parameters
      during exercise and recovery.
AB  - INTRODUCTION: Hydration plays a key role in the physiological maintenance
      required by exercise. OBJECTIVE: To evaluate the behavior of heart rate (HR),
      systolic (SBP) and diastolic (DBP) blood pressure, pulse oxygen saturation (SpO2)
      and respiratory rate (RR) of young people during and after prolonged physical
      exercise, with and without the intake of water or isotonic solution. METHOD: 31
      young individuals (21.63 +/- 1.86 years) were subjected to a four-step protocol
      with a 48-hour interval between each step, namely: i) a test to determine the
      incremental load used in subsequent steps, ii) a control protocol without
      hydration (CP), iii) an experimental protocol with water intake (PE1), iv) an
      experimental protocol with ingestion of isotonic (PE2). The protocols consisted
      of 10 min rest, 90 min of exercise on a treadmill at 60% of VO2peak and 60 min of
      recovery. The parameters HR, SBP, DBP, RR and SPO2 were measured at rest, at 30,
      60 and 90 min of exercise, with the exception of RR; and at 1, 3, 5, 7, 10, 20,
      30, 40, 50 and 60 min of recovery. The two-factor analysis of variance for
      repeated measures model was used for analysis (p<0.05). RESULTS: There was a
      moment effect for all variables in exercise (p<0.001), however, no effect was
      observed between the protocols (SBP, p=0.998; DBP, p=0.897; SpO2, p=0.077,
      HR=0.281) and in the interaction moment and protocol (SBP, p=0.058; DBP, p=0.191
      and SpO2, p=0.510, HR=0.496). In recovery there was also a moment effect for all
      variables analyzed (p<0.001). There was no effect among protocols for SBP
      (p=0.986), DBP (p=0.536) and RR (p=0.539), however in the SpO2 (p=0.001) and HR
      (p=0.033) variables, effects were observed between the protocols. Regarding the
      moment and protocol interaction, an effect was observed for HR (SBP, p=0.431;
      DBP, p=0.086; SpO2, p=0.445, RR, p=0.147, HR, p=0.022). CONCLUSION: For the type
      of exercise performed, both the water and the isotonic solution influenced the
      behavior of cardiorespiratory parameters, and independent of the type of
      hydration given the behavior of the parameters studied was similar.

PMID- 23968199
TI  - Molecular crowding drives active Pin1 into nonspecific complexes with endogenous
      proteins prior to substrate recognition.
AB  - Proteins and nucleic acids maintain the crowded interior of a living cell and can
      reach concentrations in the order of 200-400 g/L which affects the
      physicochemical parameters of the environment, such as viscosity and hydrodynamic
      as well as nonspecific strong repulsive and weak attractive interactions.
      Dynamics, structure, and activity of macromolecules were demonstrated to be
      affected by these parameters. However, it remains controversially debated, which
      of these factors are the dominant cause for the observed alterations in vivo. In
      this study we investigated the globular folded peptidyl-prolyl isomerase Pin1 in
      Xenopus laevis oocytes and in native-like crowded oocyte extract by in-cell NMR
      spectroscopy. We show that active Pin1 is driven into nonspecific weak attractive
      interactions with intracellular proteins prior to substrate recognition. The
      substrate recognition site of Pin1 performs specific and nonspecific attractive
      interactions. Phosphorylation of the WW domain at Ser16 by PKA abrogates both
      substrate recognition and the nonspecific interactions with the endogenous
      proteins. Our results validate the hypothesis formulated by McConkey that the
      majority of globular folded proteins with surface charge properties close to
      neutral under physiological conditions reside in macromolecular complexes with
      other sticky proteins due to molecular crowding. In addition, we demonstrate that
      commonly used synthetic crowding agents like Ficoll 70 are not suitable to mimic
      the intracellular environment due to their incapability to simulate biologically
      important weak attractive interactions. 

PMID- 23968200
TI  - Gold-catalyzed cyclization of 3-(2'-azidoaryl)-1-arylpropargyl carbonates or 3
      aryl-1-(2'-azidoaryl)propargyl carbonates to produce quinolines.
AB  - A gold-catalyzed cyclization of 3-(2'-azidoaryl)-1-arylpropargyl carbonates to
      generate substituted quinolines via a sequence of 3,3-rearrangement, 6-endo-trig
      cyclization and denitrogenation has been developed. Similar products could be
      obtained from 3-aryl-1-(2'-azidoaryl)propargyl carbonates under different gold
      catalytic conditions via a sequential 6-endo-dig cyclization, denitrogenation,
      and 1,2-H shift process. 

PMID- 23968201
TI  - Calcium ion contribution to thermostability of cyclodextrin glycosyltransferase
      is closely related to calcium-binding site CaIII.
AB  - In the study, we investigated the contribution of Ca2+ to the thermostability of
      alpha-cyclodextrin glycosyltransferase (alpha-CGTase) from Paenibacillus macerans
      , which has two calcium-binding sites (CaI and CaII), and beta-CGTase from
      Bacillus circulans , which contains an additional calcium-binding site (CaIII),
      consisting of Ala315 and Asp577. It was found that the contribution of Ca2+ to
      the thermostability of two CGTases displayed a marked difference. Ca2+ affected
      beta-CGTase thermostability significantly. After Ca2+ was added to beta-CGTase
      solution to a final concentration of 5 mM followed by incubation for 120 min at
      60  degrees C, residual activity of beta-CGTase was 88.3%, which was much higher
      than that without Ca2+. However, Ca2+ had a small contribution to alpha-CGTase
      thermostability. Furthermore, A315D and D577K mutations at CaIII could
      significantly change the contribution of Ca2+ to beta-CGTase thermostability.
      These results suggested that the contribution of Ca2+ to CGTase thermostability
      was closely related to CaIII.

PMID- 23968202
TI  - Atlantic salmon populations invaded by farmed escapees: quantifying genetic
      introgression with a Bayesian approach and SNPs.
AB  - BACKGROUND: Many native Atlantic salmon populations have been invaded by
      domesticated escapees for three decades or longer. However, thus far, the
      cumulative level of gene-flow that has occurred from farmed to wild salmon has
      not been reported for any native Atlantic salmon population. The aim of the
      present study was to investigate temporal genetic stability in native
      populations, and, quantify gene-flow from farmed salmon that caused genetic
      changes where they were observed. This was achieved by genotyping historical and
      contemporary samples from 20 populations covering all of Norway with recently
      identified single nucleotide polymorphism markers that are collectively
      diagnostic for farmed and wild salmon. These analyses were combined with analysis
      of farmed salmon and implementation of Approximate Bayesian computation based
      simulations. RESULTS: Five of the populations displayed statistically significant
      temporal genetic changes. All five of these populations became more similar to a
      pool of farmed fish with time, strongly suggesting introgression of farmed fish
      as the primary cause. The remaining 15 populations displayed weak or non
      significant temporal genetic changes. Estimated introgression of farmed fish
      ranged from 2-47% per population using approximate Bayesian computation. Thus,
      some populations exhibited high degrees of farmed salmon introgression while
      others were more or less unaffected. The observed frequency of escapees in each
      population was moderately correlated with estimated introgression per population
      R2 = 0.47 P < 0.001. Genetic isolation by distance existed within the historical
      and contemporary data sets, however, the among-population level of divergence
      decreased with time. CONCLUSIONS: This is the first study to quantify cumulative
      introgression of farmed salmon in any native Atlantic salmon population. The
      estimations demonstrate that the level of introgression has been population
      specific, and that the level of introgression is not solely predicted by the
      frequency of escapees observed in the population. However, some populations have
      been strongly admixed with farmed salmon, and these data provide policy makers
      with unique information to address this situation.

PMID- 23968203
TI  - VSL#3 (r) probiotic therapy does not reduce portal pressures in patients with
      decompensated cirrhosis.
AB  - BACKGROUND & AIMS: In patients with decompensated cirrhosis, bacterial
      translocation can contribute to splanchnic vasodilatation, decreased effective
      circulating volume, and portal hypertension. The primary objective of this
      randomized, double blind placebo controlled trial was to evaluate the effect of
      the probiotic VSL#3((r)) on the hepatic venous pressure gradient (HVPG). METHODS:
      Seventeen patients with decompensated cirrhosis and an HVPG of >= 10 mmHg were
      randomized to receive 2 months of VSL#3((r)) or an identical placebo. HVPG,
      endotoxin, interleukin (IL)-6, IL-8, IL-10, renin, aldosterone, nitric oxide and
      stool microbiota were measured at baseline and study end. RESULTS: Two of the 17
      patients were taken off the trial before completion (one for alcohol abuse and
      the second for SBP - both in placebo arm). Data were analysed on the remaining 15
      patients. The median model for end-stage liver disease score was 12, and 80% of
      patients had Child Pugh B disease. The treatment arm had a greater decrease in
      HVPG from baseline to study end than the placebo arm (median change from baseline
      -11.6% vs +2.8%), although this reduction was not statistically significant in
      either group. There was a significant reduction in the plasma aldosterone level
      in the VSL#3((r)) group, but no significant changes in the other measured
      parameters, including the stool microflora analysis. CONCLUSIONS: Within the
      limitations of our sample size, VSL#3((r)) therapy does not appear to have a
      significant impact on portal pressure reduction in patients with decompensated
      cirrhosis.

PMID- 23968204
TI  - Transmitted HIV resistance among pregnant young women infected with HIV-1 in
      Brazil.

PMID- 23968205
TI  - Health impact of incarceration on HIV-positive African American males: a
      qualitative exploration.
AB  - Previous research suggests that incarceration can have a negative effect on
      health. These health effects have an especially profound impact on HIV-positive
      individuals. As such, the current study investigates how incarceration affects
      the health of 12 African American HIV-positive formerly incarcerated males
      recruited via an AIDS Service Organization. Individuals were enrolled via
      purposive sampling and engaged in a series of in-depth interviews over a yearlong
      period (n=46). Participants ranged in age from 33 to 61 years. Most had finished
      high school, were not employed at time of first and last interview, and most were
      primarily residing at a homeless shelter. The time incarcerated ranged among
      participants from 3 months to 3 years. Findings suggest that health is impacted
      via limited and delayed access to medication, stigma, and poor quality of medical
      care while incarcerated. Health continues to worsen after release, largely due to
      incarceration's impact on individuals' social context. Macro-level policy limits
      opportunity to fulfill basic needs such as housing and hinders one's ability to
      be gainfully employed. Moreover, stigma, loss of social support, and a delay in
      accessing HIV-related services deleteriously impacts individuals' mental and
      physical health status. Implications for practice, policy and future research are
      also discussed.

PMID- 23968206
TI  - Psychometric evaluation of a cross-culturally adapted felt stigma questionnaire
      among people living with HIV in Kenya.
AB  - Psychometric properties of an 18-item HIV felt stigma questionnaire were
      evaluated utilizing data collected from a diverse ethnic and socioeconomic group
      of 370 people living with HIV/AIDS and receiving HIV/AIDS-related health services
      at an HIV clinic in Kenya. Factor analyses revealed a four factor solution
      (public attitudes, ostracize, discrimination, personal life disrupted) based on
      the Scree plot with explained variance of 44% that had Eigen values greater than
      1.00. The retained felt stigma items revealed a Cronbach's alpha coefficient of
      0.828, while the four factors had coefficient alphas ranging from 0.675 to 0.799.
      The adapted retained questionnaire was deemed a practical guide for measuring
      felt stigma in a Kenyan cultural context to necessitate provision of the most
      effective HIV-related mental health services to individuals living with HIV in
      Kenya.

PMID- 23968208
TI  - Mental rotation studied by functional magnetic resonance imaging at high field (4
      tesla): performance and cortical activation.
AB  - We studied the performance and cortical activation patterns during a mental
      rotation task (Shepard & Metzler, 1971) using functional magnetic resonance
      imaging (fMlU) at high field (4 Tesla). Twenty-four human subjects were imaged
      (fMRI group), whereas six additional subjects performed the task without being
      imaged (control group). All subjects were shown pairs of perspective drawings of
      31, objects and asked to judge whether they were the same or mirror images. The
      measures of performance examined included (1) the percentage of errors, (2) the
      speed of performance, calculated as the inverse of the average response time, and
      (3) the rate of rotation for those object pairs correctly identified as "same."
      We found the following: (1) Subjects in the fMRI group performed well outside and
      inside the magnet, and, in the latter case, before and during data acquisition.
      Moreover, performance over time improved in the same manner as in the control
      group. These findings indicate that exposure to high magnetic fields does not
      impair performance in mental rotation. (2) Functional activation data were
      analyzed from 16 subjects of the fMRI goup. Several cortical areas were activated
      during task performance. The relations between the measures of performance above
      and the magnitude of activation of specific cortical areas were investigated by
      anatomically demarcating these areas of interest and calculating a normalized
      activation for each one of them. (3) We used the multivariate technique of
      hierarchical tree modeling to determine functional clustering among areas of
      interest and performance measures. Two main branches were distinguished: One
      comprised areas in the right hemisphere and the extrastriate and superior
      parietal lobules bilaterally, whereas the other comprised areas of the left
      hemisphere and the frontal pole bilaterally; all three performance measures above
      clustered with the former branch. Specifically, performance outcome ("percentage
      of errors") clustered with the parieto-occipital subcluster, whereas both the
      speed of performance and the rate of mental rotation clustered with the right
      precentral gyms. We conclude that the mental rotation paradigm used involves the
      cooperative interaction of functional groups of cortical areas of which some are
      probably more specifically associated with performance, whereas others may serve
      a more general function within the task constraints. 

PMID- 23968209
TI  - Transcranial magnetic stimulation of the prefrontal cortex delays contralateral
      endogenous saccades.
AB  - The contributions of the superior prefrontal cortex (SPFC) and the superior
      parietal lobule (SPL) in generating voluntary endogenous and reflexive visually
      guided saccades were investigated using transcranial magnetic stimulation (TMS).
      Subjects made choice saccades to the left or right visual field in response to a
      central arrowhead (endogenous go signal) or a peripheral asterisk (exogenous go
      signal) that were presented along with a single TMS pulse at varying temporal
      intervals. TMS over the SPFC increased latencies for saccades made in response to
      an endogenous go signal toward the contralateral hemifield. No effects were
      observed when the go signal was exogenous and TMS was over the SPFC or when TMS
      was over the SPL for either saccade type. The delayed contralateral endogenous
      saccades observed in this study are likely a consequence of disruption in the
      normal operations of the human frontal eye field. 

PMID- 23968210
TI  - The neural substrate for concrete, abstract, and emotional word lexica a positron
      emission tomography study.
AB  - Viewing of single words produces a cognitively complex mental state in which
      anticipation, emotional responses, visual perceptual analysis, and activation of
      orthographic representations are all occurring. Previous PET studies have
      produced conflicting results, perhaps due to the conflation of these separate
      processes or the presence of subtle differences in stimulus material and
      methodology. A PET study of 10 normal individuals was carried out using the bolus
      H2(15)O intravenous injection technique to examine components of processing of
      passively viewed words. Subjects viewed blocks of random-letter strings or
      abstract, concrete, or emotional words (words with positive or negative emotional
      salience). Baseline conditions were either passive viewing of plus signs or an
      anticipatory state (viewing plus signs after being warned to expect words or
      random letters to appear imminently). All words (and to a lesser extent the
      random letters) produced robust activation of cerebral blood flow in the left
      posterior temporal lobe, in addition to bilateral occipital activation.
      Furthermore, emotional words produced activation in orbital and midline frontal
      structures. Further activation in the left orbital frontal gyrus, the left
      inferior temporal gyrus, the left caudate nucleus, the anterior cingulate, and
      the cerebellum could be ascribed to the anticipatory state. This pattern of
      activity suggests that the occipital regions are recruited for visual-perceptual
      analysis of words, and the left temporal lobe represents the neural substrate for
      the orthographic lexicon. In addition, emotionally relevant material produces
      further processing in limbic brain structures of the frontal lobes. Detailed
      analysis of the task therefore substantially clarifies the neuroanatomic basis of
      single-word processing. 

PMID- 23968211
TI  - Verbal Working Memory Load Affects Regional Brain Activation as Measured by PET.
AB  - We report an experiment that assesses the effect of variations in memory load on
      brain activations that mediate verbal working memory. The paradigm that forms the
      basis of this experiment is the "n-back" task in which subjects must decide for
      each letter in a series whether it matches the one presented n items back in the
      series. This task is of interest because it recruits processes involved in both
      the storage and manipulation of information in working memory. Variations in task
      difficulty were accomplished by varying the value of n. As n increased, subjects
      showed poorer behavioral performance as well as monotonically increasing
      magnitudes of brain activation in a large number of sites that together have been
      identified with verbal working-memory processes. By contrast, there was no
      reliable increase in activation in sites that are unrelated to working memory.
      These results validate the use of parametric manipulation of task variables in
      neuroimaging research, and they converge with the subtraction paradigm used most
      often in neuroimaging. In addition, the data support a model of working memory
      that includes both storage and executive processes that recruit a network of
      brain areas, all of which are involved in task performance. 

PMID- 23968212
TI  - Visual imagery facilitates visual perception: psychophysical evidence.
AB  - Visual imagery is the invention or recreation of a perceptual experience in the
      absence of retinal input.The degree to which the same neural representations are
      involved in both visual imagery and visual perception is unclear. Previous
      studies have shown that visual imagery interferes with perception (Perky effect).
      We report here psychophysical data showing a direct facilitatory effect of visual
      imagery on visual perception. Using a lateral masking detection paradigm of a
      Gabor target, flanked by peripheral Gabor masks, observers performed imagery
      tasks that were preceded by perceptual tasks. We found that both perceived and
      imaginary flanking masks can reduce contrast detection threshold. At short target
      to-mask distances imagery induced a threshold reduction of 50% as compared with
      perception, while at long target-to-mask distances imagery and perception had
      similar facilitatory effect. The imagery-induced facilitation was specific to the
      orientation of the stimulus, as well as to the eye used in the task. These data
      indicate the existence of a stimulus-specific short-term memory system that
      stores the sensory trace and enables reactivation of quasi-pictorial
      representations by topdown processes. We suggest that stimulus parameters
      dominate the imagery-induced facilitation at short target-to-mask distances, yet
      the topdown component contributes to the effect at long target-to-mask distances.

PMID- 23968213
TI  - Intact perceptual priming in a patient with damage to the anterior inferior
      temporal lobes.
AB  - We conducted three experiments to examine whether the anterior portion of the
      inferior temporal (IT) lobe is involved in the processing of visual objects in
      humans. In monkeys, damage to this region results in severe deficits in
      perception and in memory for visual objects. Our study was designed to examine
      both these processes in a patient (DM) with bilateral damage to the anterior
      portion of the inferior temporal lobe. Neuropsychological examination revealed a
      significant semantic impairment and a mild deficit in the discrimination of
      familiar objects from nonobjects. Despite these difficulties, the results of
      several studies indicated that DM was able to form and retain descriptions of the
      structure of objects. Specifically, DM showed normal perceptual priming for
      familiar and novel objects on implicit memory tests, even when the objects were
      transformed in size and left-right orientation. These results suggest that the
      anterior IT is not'involved in (1) the storage of pre-existing structural
      descriptions of known objects, (2) the ability to create new structural
      descriptions for novel objects, and (3) the ability to compute descriptions that
      are invariant with respect to changes in size and reflection. Instead, the
      anterior IT appears to provide the interface between structural descriptions of
      objects and their meanings. 

PMID- 23968214
TI  - Mamillary Body Lesions in Monkeys Impair Object-in-Place Memory: Functional Unity
      of the Fornix-Mamillary System.
AB  - Six monkeys were trained preoperatively in an automated object-in-place memory
      task in which they learned 20 new scenes in each daily session. Three of the six
      monkeys then received stereotaxically guided bilateral mamillary body lesions,
      leaving the fornix intact, while the other three received a control operation.
      Postoperatively the control animals' rate of learning new scenes was unchanged,
      but the animals with mamillary body lesions showed a severe impairment, equal to
      that seen in previous experiments after fornix transection. All six animals were
      then given fornix transection, in addition to the existing mamillary or control
      operation. The control group now showed, after fornix transection, an impairment
      equal to that of the animals with mamillary body lesions alone. But the animals
      with mamillary body lesions did not show any additional impairment following
      fornix transection. We conclude that (1) the role of the mamillary bodies in a
      model of human episodic memory is as important as the role of the fornix, (2) the
      fornix and mamillary bodies form a single functional memory system, since the
      effect of lesions in both parts is no more severe than the effects of a lesion in
      one of the parts alone, and (3) the idea that the functional effects of fornix
      transection result from cholmergic deafferentation of the hippocampus receives no
      support from the present results; rather, they support the idea that in primates
      the fornix and mamillary bodies, together with connected structures, including
      the subiculum, mamillo-thalamic tract, anterior thalamic nuclei, and cingulate
      bundle, form a cortico-cortical association pathway for episodic memory. 

PMID- 23968215
TI  - Higher-order associative learning in amnesia: evidence from the serial reaction
      time task.
AB  - Patients with anterograde amnesia are commonly believed to exhibit normal
      implicit learning. Research with the serial reaction time (SRT) task suggests
      that normal subjects can implicitly learn visuospatial sequences through a
      process that is sensitive to higher-order information that is more complex than
      pairwise associations between adjacent stimuli. The present research reexamined
      SRT learning in a group of amnesic patients with a design intended to
      specifically address the learning of higher-order information. Despite seemingly
      normal learning effects on average, the results suggest that amnesic patients do
      not learn higher-order information as well as control subjects. These results
      suggest that amnesic patients have an associative learning impairment, even when
      learning is implicit, and that the medial temporal lobe and/or diencephalic brain
      areas typically damaged in cases of amnesia normally contribute to implicit
      sequence learning. 

PMID- 23968216
TI  - Effects of early and late nocturnal sleep on declarative and procedural memory.
AB  - Recall of paired-associate lists (declarative memory) and mirror-tracing skills
      (procedural memory) was assessed after retention intervals defined over early and
      late nocturnal sleep. In addition, effects of sleep on recall were compared with
      those of early and late retention intervals filled with wakefulness. Twenty
      healthy men served as subjects. Saliva cortisol concentrations were determined
      before and after the retention intervals to determine pituitary-adrenal secretory
      activity. Sleep was determined somnopolygraphically. Sleep generally enhanced
      recall when compared with the effects of corresponding retention intervals of
      wakefulness. The benefit from sleep on recall depended on the phase of sleep and
      on the type of memory: Recall of paired-associate lists improved more during
      early sleep, and recall of mirror-tracing skills improved more during late sleep.
      The effects may reflect different influences of slow wave sleep (SWS) and rapid
      eye movement (REM) sleep since time in SWS was 5 times longer during the early
      than late sleep retention interval, and time in REM sleep was twice as long
      during late than early sleep (p < 0.005). Changes in cortisol concentrations,
      which independently of sleep and wakefulness were lower during early retention
      intervals than late ones, cannot account for the effects of sleep on memory. The
      experiments for the first time dissociate specific effects of early and late
      sleep on two principal types of memory, declarative and procedural, in humans. 

PMID- 23968217
TI  - Parents of Children with Asperger Syndrome: What is the Cognitive Phenotype?
AB  - Two cognitive anomalies have been found in autism: a superiority on the Embedded
      Figures Task and a deficit in "theory of mind." Using adult-level versions of
      these tasks, the present study investigated if parents of children with Asperger
      Syndrome might show a mild variant of these anomalies, as might be predicted from
      a genetic hypothesis. Significant differences were found on both measures.
      Parents were significantly faster than controls on the Embedded Figures Task and
      slightly but significantly less accurate at interpreting photographs of the eye
      region of the face in terms of mental states. The results are discussed in terms
      of the broader cognitive phenotype of Asperger Syndrome and in terms of their
      implications for cognitive neuroscientific theories of the condition. 

PMID- 23968218
TI  - Self-concept organisation and mental toughness in sport.
AB  - The present study examines the relationship between individual differences in
      evaluative self-organisation and mental toughness in sport, proposing that
      motivation and emotional resiliency (facets of mental toughness) stem from
      differences in core self. A cross-sectional assessment of 105 athletes competing
      at a range of performance levels took part in an online study including measures
      of self-reported mental toughness (Sport Mental Toughness Questionnaire; Sheard,
      M., Golby, J., & van Wersch, A. (2009). Progress towards construct validation of
      the Sports Mental Toughness Questionnaire (SMTQ). European Journal of
      Psychological Assessment, 25(3), 186-193. doi:10.1027/1015-5759.25.3.186) and
      self-organisation (self-descriptive attribute task; Showers, C. J. (2002).
      Integration and compartmentalisation: A model of self-structure and self-change.
      In D. Cervone & W. Mischel (Eds.), Advances in personality science (pp. 271-291).
      New York, NY: Guilford Press). As predicted, global mental toughness was
      associated with self-concept positivity, which was particularly high in
      individuals with positive-integrative self-organisation (individuals who
      distribute positive and negative self-attributes evenly across multiple selves).
      Specifically, positive integration was associated with constancy (commitment to
      goal achievement despite obstacles and the potential for failure), which extends
      presumably from positive integratives' emotional stability and drive to resolve
      negative self-beliefs.

PMID- 23968219
TI  - Thermally modulated porous silica multispectral filters and their application in
      remote imaging.
AB  - We report a thermally tunable multispectral imaging filter based on reversible
      condensation of volatile organic fluids within a nanoporous one-dimensional
      photonic crystal. The photonic crystal (optical rugate filter) comprises oxidized
      porous silicon, prepared by electrochemical etch of silicon and subsequent air
      oxidation (porous silica rugate filter, pSiF). The reflectance spectrum of the
      pSiF is designed and constructed to match two of the red emission bands of the
      luminescent complex europium(III) tris-dipicolinate, [Eu(dpa)3](3-), which has
      been used as an indicator for anthrax spores. When the pSiF is fitted with a
      thermoelectric Peltier cooler/heater and sealed in a container with 2-propanol
      vapor, microcapillary effects drive the temperature-dependent
      condensation/evaporation of 2-propanol into/out of the porous nanostructure.
      Thermal cycling experiments show that the wavelengths of the spectral bands of
      the pSiF are reversibly tuned by +/-35 nm for a temperature change of +/-40 
      degrees C. Difference images of a UV-illuminated scene containing the
      [Eu(dpa)3](3-) target, obtained by reflection from pSiF that is continuously
      thermally cycled through the emission bands of the dye, show that the target can
      be discriminated from the background or from control targets with overlapping but
      dissimilar luminescence spectra. 

PMID- 23968220
TI  - Is volunteering a public health intervention? A systematic review and meta
      analysis of the health and survival of volunteers.
AB  - BACKGROUND: Volunteering has been advocated by the United Nations, and American
      and European governments as a way to engage people in their local communities and
      improve social capital, with the potential for public health benefits such as
      improving wellbeing and decreasing health inequalities. Furthermore, the US
      Corporation for National and Community Service Strategic Plan for 2011-2015
      focused on increasing the impact of national service on community needs,
      supporting volunteers' wellbeing, and prioritising recruitment and engagement of
      underrepresented populations. The aims of this review were to examine the effect
      of formal volunteering on volunteers' physical and mental health and survival,
      and to explore the influence of volunteering type and intensity on health
      outcomes. METHODS: Experimental and cohort studies comparing the physical and
      mental health outcomes and mortality of a volunteering group to a non
      volunteering group were identified from twelve electronic databases (Cochrane
      Library, Medline, Embase, PsychINFO, CINAHL, ERIC, HMIC, SSCI, ASSIA, Social Care
      Online, Social Policy and Practice) and citation tracking in January 2013. No
      language, country or date restrictions were applied. Data synthesis was based on
      vote counting and random effects meta-analysis of mortality risk ratios. RESULTS:
      Forty papers were selected: five randomised controlled trials (RCTs, seven
      papers); four non-RCTs; and 17 cohort studies (29 papers). Cohort studies showed
      volunteering had favourable effects on depression, life satisfaction, wellbeing
      but not on physical health. These findings were not confirmed by experimental
      studies. Meta-analysis of five cohort studies found volunteers to be at lower
      risk of mortality (risk ratio: 0.78; 95% CI: 0.66, 0.90). There was insufficient
      evidence to demonstrate a consistent influence of volunteering type or intensity
      on outcomes. CONCLUSION: Observational evidence suggested that volunteering may
      benefit mental health and survival although the causal mechanisms remain unclear.
      Consequently, there was limited robustly designed research to guide the
      development of volunteering as a public health promotion intervention. Future
      studies should explicitly map intervention design to clear health outcomes as
      well as use pragmatic RCT methodology to test effects.

PMID- 23968222
TI  - Frontal fibrosing alopecia in an African man.

PMID- 23968221
TI  - Lactate uptake by the injured human brain: evidence from an arteriovenous
      gradient and cerebral microdialysis study.
AB  - Lactate has been regarded as a waste product of anaerobic metabolism of glucose.
      Evidence also suggests, however, that the brain may use lactate as an alternative
      fuel. Our aim was to determine the extent of lactate uptake from the circulation
      into the brain after traumatic brain injury (TBI) and to compare it with levels
      of lactate in the brain extracellular fluid. We recruited 19 patients with
      diffuse TBI, monitored with cerebral microdialysis and jugular bulb catheters.
      Serial arteriovenous (AV) concentration differences of glucose and lactate were
      calculated from arterial and jugular blood samples, providing a measure of net
      uptake or export by the brain. Microdialysis was used to measure brain
      extracellular glucose and lactate. In 17/19 patients studied for 5 days post
      injury, there were periods of net lactate uptake into the brain, most frequently
      on day 3 after injury. Brain microdialysate lactate had a median (interquartile
      range [IQR]) concentration of 2.5 (1.5-3.2) mmol/L during lactate uptake and 2.2
      (1.7-3.0) mmol/L during lactate export. Lactate uptake into the brain occurred at
      a median (IQR) arterial lactate concentration of 1.6 (1.0-2.2) mmol/L. Lactate
      uptake was associated with significantly higher AV difference in glucose values
      with a median (IQR) of 0.4 (0.03-0.7) mmol/L during uptake and 0.1 (-0.2-0.3)
      mmol/L during lactate export (Mann-Whitney U p=0.003). Despite relatively high
      brain lactate compared with arterial lactate concentrations, the brain appears to
      up-regulate lactate transport into the brain after TBI. This may serve to satisfy
      greater demands for energy substrate from the brain after TBI.

PMID- 23968223
TI  - A comparison of the predicted risk for cardiovascular disease between HIV
      infected and uninfected persons in Korea.
AB  - BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) has
      extended the life expectancy of persons infected with the human immunodeficiency
      virus type 1 (HIV-1). However, cardiovascular disease (CVD) is currently an
      increasing concern for HIV-infected persons. METHODS: We conducted a cross
      sectional case-control study to evaluate and compare the 10-y cardiovascular risk
      of HIV-infected Koreans who had been receiving HAART for over 6 months and age-
      and sex-matched uninfected persons who visited a health promotion center, by
      calculating Framingham risk scores (FRS). RESULTS: The average 10-y risk for
      cardiovascular events (FRS) was 7.07% (2-45) in the HIV group and 6.87% (1-37) in
      the control group (p = 0.77), corresponding to the very low risk group. Among HIV
      patients, the FRS was above 10% (low to moderate cardiovascular risk) in 19.9% of
      the patients, and above 20% (high risk) in 1.7% of the patients. In the healthy
      control group, the FRS was above 10% in 16.8% and above 20% in 2.7% (p = 0.57).
      The FRS was not significantly different for HIV-infected patients treated with
      protease inhibitor (PI)-based HAART and those treated with non-nucleoside reverse
      transcriptase inhibitor (NNRTI)-based HAART (7.26 +/- 6.3 and 6.81 +/- 4.4,
      respectively, p = 0.69). CONCLUSIONS: The predicted cardiovascular risk of HIV
      infected Koreans on HAART by FRS equation was low and similar to that of age- and
      sex-matched healthy control persons. However, the possibility remains that actual
      cardiovascular events could be underestimated. The next step for predicting the
      cardiovascular risk is to calculate the Data Collection of Adverse Events of Anti
      HIV Drugs (D:A:D) equation risks.

PMID- 23968224
TI  - Patterns of treatment of reported malaria cases during pregnancy in a Nigerian
      hospital.
AB  - BACKGROUND: Prompt and effective case management is one of the control measures
      for malaria during pregnancy. The objective of the study was to assess treatment
      patterns of presumed cases of malaria during pregnancy in a Nigerian tertiary
      health care facility. METHODS: A cross-sectional study involving immediate
      postpartum women admitted to the maternity wards of the University of Benin
      Teaching Hospital was undertaken. History of occurrence and treatment practices
      of presumed malaria during the immediate past pregnancy were obtained from the
      women's medical case files and by interview, using a pre-developed data
      collection form. RESULTS: Two hundred and ninety-seven of the 428 study
      participants (69.4%) reported a total number of 544 cases of malaria in pregnancy
      (MiP). More than 85% (n = 469/544) of the reported MiP cases occurred after the
      first trimester, while 55.5% (302/544) occurred during the second trimester.
      Among the reported MiP cases, parasite-based diagnosis was done for only 8.6% (n
      = 47). The use of antimalarial medications was reported in the treatment of 86.6%
      of the total number of cases. Antimalarial medication was used across the 3
      trimesters, including artemisinin-based combination therapy (49.6%), artemisinin
      monotherapy (15.2%), and other monotherapies, such as sulfadoxine-pyrimethamine,
      chloroquine, amodiaquine (33.3%), and oral quinine (2%). Sulfadoxine
      pyrimethamine and artemisinin derivatives were used in the treatment of 38.8% and
      34.7% of first trimester malaria cases, respectively. CONCLUSIONS: Parasite-based
      diagnosis prior to treatment was poorly practiced, and inappropriate antimalarial
      drug management of MiP was observed. Addressing these observed deficiencies is
      necessary in order to achieve success in the fight against malaria during
      pregnancy in Nigeria.

PMID- 23968225
TI  - Bacterial meningitis in children in Iceland, 1975-2010: a nationwide
      epidemiological study.
AB  - BACKGROUND: Bacterial meningitis is a serious and potentially rapid life
      threatening disease. Therefore, to ensure appropriate treatment, early
      recognition of signs and symptoms is imperative, along with knowledge of the
      epidemiology and microbiology of the disease. METHODS: A long-term, nationwide
      epidemiological study of bacterial causes of meningitis in children (<= 18 y) in
      Iceland during the period 1975-2010 was carried out. A detailed chart review was
      performed of all cases diagnosed in 1995-2010. RESULTS: A total of 477 children
      were diagnosed with bacterial meningitis during the period 1975-2010. Of these,
      67% were aged under 5 y. The most common pathogens were Neisseria meningitidis (n
      = 265), Haemophilus influenzae (n = 132), Streptococcus pneumoniae (n = 47), and
      Streptococcus agalactiae (n = 19); their incidences varied according to age. The
      age-specific incidence (cases/100,000/y) dropped from 26 in 1975 to 1 in 2010 (p
      < 0.001). The most common symptoms during the period 1995-2010 were fever (92%),
      vomiting (67%), nuchal rigidity (60%), and rashes/petechiae (51%). H. influenzae
      type b disappeared following implementation of Hib vaccination in 1989, and,
      likewise, the incidence of meningococcal meningitis fell significantly after
      vaccination against meningococcus serogroup C was initiated in 2002 (p < 0.001).
      The overall 30-day case fatality rate of bacterial meningitis was 4.4% and
      remained unchanged during the study period. CONCLUSIONS: The incidence of
      childhood bacterial meningitis has been reduced significantly by successful
      vaccinations against H. influenzae type b and N. meningitidis serogroup C.
      Nevertheless, the case fatality rate has remained unchanged and thus the disease
      is still a serious threat to childhood health. Further prevention by novel
      vaccines and improved management of childhood meningitis is an exciting
      challenge.

PMID- 23968226
TI  - Facile and green synthesis of core-shell structured magnetic chitosan
      submicrospheres and their surface functionalization.
AB  - Submicrometer-sized magnetite colloid nanocrystal clusters (MCNCs) provide a new
      avenue for constructing uniformly sized and highly magnetic composite
      submicrospheres. Herein, a facile and eco-friendly method is described for the
      synthesis of Fe3O4@poly(acrylic acid) (PAA)/chitosan (CS) core-shell
      submicrospheres using MCNCs bearing carboxyl groups as the magnetic cores. It is
      based on the self-assembly of positively charged CS chains on the surface of the
      oppositely charged MCNCs dispersed in the aqueous solution containing acrylic
      acid (AA) and a cross-linker N,N'-methylenebis(acrylamide) (MBA), followed by
      radical induced cross-linking copolymerization of AA and MBA along the CS chains.
      The resulting polymer shell comprises a medium shell of cross-linked PAA/CS
      polyelectrolyte complexes and an outer shell of protonated CS chains. It was
      found that the shell thickness could be tuned by varying either the concentration
      of radical initiator or the molar ratio of AA to aminoglucoside units of CS. To
      the surface of thus obtained Fe3O4@PAA/CS particles, Au nanoparticles, a variety
      of functional groups such as fluorescein, carboxyl, quaternary ammonium, and
      aliphatic bromide, and even functional polymer chains were successfully
      introduced. Therefore, such Fe3O4@PAA/CS submicrospheres may be used as versatile
      magnetic functional scaffolds in biorelated areas like bioseparation and medical
      assay, considering the unique features of CS like nontoxicity and
      biocompatibility. 

PMID- 23968227
TI  - Fixed drug eruption in Bangladeshi population: confirmed by provocative test.
AB  - BACKGROUND: Fixed drug eruption is designated as a typical allergic reaction
      occurring due to exposure to a medicine. This common dermatological condition is
      often being ignored for its causative agent as well as the patient's sufferings
      sometimes become unpredictable. AIMS: The objective of this large population
      study is to identify the causative agents responsible for fixed drug eruption.
      MATERIALS & METHODS: The study is comprised of 120 suspected patients of fixed
      drug eruption. History, classic clinical features of well circumscribed erythema,
      edema, and violaceous pigmentation, and the recurrence of the eruptions on the
      same sites upon re-administering drug were used as diagnostic criteria. The
      drug(s) causing allergic reactions were confirmed by provocation tests. RESULTS:
      The incidence of drug eruption was found distributed in 0.62% amongst all
      dermatology outpatient attendees. The male to female ratio recorded was 7:2. The
      highest number of cases was observed within in the age group of 21-35 years. The
      provocation tests were positive in 92 among 120. The genitalia and lips/face were
      the most commonly affected site for fixed drug eruption. DISCUSSION: The drug
      sulphonamide (including co-trimoxazole) accounted for the highest number of cases
      of eruptions (28.33 %). The other drugs, in order of frequency, responsible for
      the cause of eruptions were identified as nonsteroidal anti-inflammatory drugs,
      tetracycline, metronidazole, herbal medicine, paracetamol, fluconazole,
      penicillin, Griseofulvin, and homeopathic medicine, etc. CONCLUSION: Drug
      reactions are very frequently experienced by dermatologists in their day-to-day
      practice. The patients are often ignorant of the drugs consumed and often do not
      accept them as an etiologic factor. A detailed drug history as well as the
      complaints will be helpful before undertaking the provocation test.

PMID- 23968229
TI  - Morphology and property control of NiO nanostructures for supercapacitor
      applications.
AB  - We process one-dimensional (1D) NiO nanostructures in anodized alumina templates
      starting from electrochemically deposited Ni nanotubes (NTs), and characterize
      their morphology-dependent supercapacitance behavior. The morphology of the 1D
      NiO nanostructures is controlled by the time of annealing at 450 degrees C. After
      25 min of annealing, the NTs start to close but maintain the tubular structure,
      and after a further 300 min of annealing time, the tubes are completely closed
      and nanorods (NRs) are formed. We show that the structures obtained are highly
      promising for supercapacitor applications; the performance of the NiO NT
      structure is with a specific capacitance of 2,093 F/g, the highest ever obtained
      for NiO, approaching the theoretical capacitance of this material. A suitable
      combination of nanocrystalline grain size and the high surface area akin to the
      tubular structure is responsible for this high performance. In contrast, the NiO
      NR structure is characterized by lower performance (797 F/g). A further attribute
      of the proposed structure is its high stability against galvanostatic charging
      discharging cycling at high current densities, with almost no alteration to
      performance after 500 cycles. 

PMID- 23968228
TI  - Traits of fear resistance and susceptibility in an advanced intercross line.
AB  - Genetic variability in the strength and precision of fear memory is hypothesised
      to contribute to the etiology of anxiety disorders, including post-traumatic
      stress disorder. We generated fear-susceptible (F-S) or fear-resistant (F-R)
      phenotypes from an F8 advanced intercross line (AIL) of C57BL/6J and DBA/2J
      inbred mice by selective breeding. We identified specific traits underlying
      individual variability in Pavlovian conditioned fear learning and memory.
      Offspring of selected lines differed in the acquisition of conditioned fear.
      Furthermore, F-S mice showed greater cued fear memory and generalised fear in
      response to a novel context than F-R mice. F-S mice showed greater basal
      corticosterone levels and hypothalamic corticotrophin-releasing hormone (CRH)
      mRNA levels than F-R mice, consistent with higher hypothalamic-pituitary-adrenal
      (HPA) axis drive. Hypothalamic mineralocorticoid receptor and CRH receptor 1 mRNA
      levels were decreased in F-S mice as compared with F-R mice. Manganese-enhanced
      magnetic resonance imaging (MEMRI) was used to investigate basal levels of brain
      activity. MEMRI identified a pattern of increased brain activity in F-S mice that
      was driven primarily by the hippocampus and amygdala, indicating excessive limbic
      circuit activity in F-S mice as compared with F-R mice. Thus, selection pressure
      applied to the AIL population leads to the accumulation of heritable trait
      relevant characteristics within each line, whereas non-behaviorally relevant
      traits remain distributed. Selected lines therefore minimise false-positive
      associations between behavioral phenotypes and physiology. We demonstrate that
      intrinsic differences in HPA axis function and limbic excitability contribute to
      phenotypic differences in the acquisition and consolidation of associative fear
      memory. Identification of system-wide traits predisposing to variability in fear
      memory may help in the direction of more targeted and efficacious treatments for
      fear-related pathology. 

PMID- 23968230
TI  - Massive hemoptysis and complete unilateral lung collapse in pregnancy due to
      pulmonary tuberculosis with good maternal and fetal outcome: a case report.
AB  - BACKGROUND: We report an extremely rare case of massive hemoptysis and complete
      left-sided lung collapse in pregnancy due to pulmonary tuberculosis in a health
      care worker with good maternal and fetal outcome. CASE PRESENTATION: A 33-year
      old human immuno deficiency virus seronegative African health care worker in her
      fourth pregnancy with two previous second trimester miscarriages and an
      apparently healthy daughter from her third pregnancy presented coughing up
      copious amounts of blood at 18 weeks and two days of gestation. She had a
      cervical suture in situ for presumed cervical weakness. Computed tomography of
      her chest showed complete collapse of the left lung; subsequent bronchoscopy was
      apparently normal. Her serum beta-human chorionic gonadotropin, tests for
      autoimmune disease and echocardiography were all normal. Her lung re-inflated
      spontaneously. Sputum for acid alcohol fast bacilli was positive; our patient was
      commenced on anti-tuberculosis medication and pyridoxine. At 41 weeks and three
      days of pregnancy our patient went into spontaneous labor and delivered a live
      born female baby weighing 2.6 kg with APGAR scores of nine and 10 at one and five
      minutes respectively. She and her baby are apparently doing well about 10 months
      after delivery. CONCLUSION: It is possible to have massive hemoptysis and
      complete unilateral lung collapse with spontaneous resolution in pregnancy due to
      pulmonary tuberculosis with good maternal and fetal outcome.

PMID- 23968231
TI  - Supporting health systems in Europe: added value of EU actions?
AB  - Since the start of the economic crisis, the European Union's (EU's) predominant
      discourse has been austerity and fiscal consolidation. The detrimental effects on
      Europe's health systems and the health status of its citizens are well described.
      However, little is known about the emerging EU-level initiatives to support
      national health systems handle the challenges of efficient care provision and
      system reorganisation aimed to meet their future needs. This review analyses the
      manner, conditions and prospects of such EU support. First, health system
      objectives are increasingly entering the EU health policy agenda. Second,
      professional and patient mobility provisions may support member states (MS) in
      copying with crisis related health challenges but can potentially acerbate them
      at the same time. Third, in recent initiatives health system goals are more
      closely tied to the EU's economic growth narrative. And fourth, health system
      issues are taken up in existing EU-level structures for debate and exchange
      between MS. In addition, the design of some policies may have the potential to
      intensify socioeconomic and health inequalities rather than ameliorate them. 

PMID- 23968232
TI  - Stereocontrolled synthesis of 1,3-diols from enones: cooperative Lewis base
      mediated intramolecular carbonyl hydrosilylations.
AB  - A streamlined synthesis of beta-hydroxy ketone substrates has been developed to
      further investigate a recently discovered cooperative Lewis base-mediated
      intramolecular carbonyl hydrosilylation reaction. The synthesis features an enone
      beta-borylation/oxidation sequence that has proven to be quite general and high
      yielding. This has allowed for additional investigations into the
      diastereoselectivity of the hydrosilylation reaction through the preparation of
      important polyketide fragments. 

PMID- 23968233
TI  - Structure-guided discovery of new deaminase enzymes.
AB  - A substantial challenge for genomic enzymology is the reliable annotation for
      proteins of unknown function. Described here is an interrogation of
      uncharacterized enzymes from the amidohydrolase superfamily using a structure
      guided approach that integrates bioinformatics, computational biology, and
      molecular enzymology. Previously, Tm0936 from Thermotoga maritima was shown to
      catalyze the deamination of S-adenosylhomocysteine (SAH) to S-inosylhomocysteine
      (SIH). Homologues of Tm0936 homologues were identified, and substrate profiles
      were proposed by docking metabolites to modeled enzyme structures. These enzymes
      were predicted to deaminate analogues of adenosine including SAH, 5'
      methylthioadenosine (MTA), adenosine (Ado), and 5'-deoxyadenosine (5'-dAdo).
      Fifteen of these proteins were purified to homogeneity, and the three-dimensional
      structures of three proteins were determined by X-ray diffraction methods. Enzyme
      assays supported the structure-based predictions and identified subgroups of
      enzymes with the capacity to deaminate various combinations of the adenosine
      analogues, including the first enzyme (Dvu1825) capable of deaminating 5'-dAdo.
      One subgroup of proteins, exemplified by Moth1224 from Moorella thermoacetica,
      deaminates guanine to xanthine, and another subgroup, exemplified by Avi5431 from
      Agrobacterium vitis S4, deaminates two oxidatively damaged forms of adenine: 2
      oxoadenine and 8-oxoadenine. The sequence and structural basis of the observed
      substrate specificities were proposed, and the substrate profiles for 834 protein
      sequences were provisionally annotated. The results highlight the power of a
      multidisciplinary approach for annotating enzymes of unknown function. 

PMID- 23968234
TI  - Chromosome rearrangements, recombination suppression, and limited segregation
      distortion in hybrids between Yellowstone cutthroat trout (Oncorhynchus clarkii
      bouvieri) and rainbow trout (O. mykiss).
AB  - BACKGROUND: Introgressive hybridization is an important evolutionary process that
      can lead to the creation of novel genome structures and thus potentially new
      genetic variation for selection to act upon. On the other hand, hybridization
      with introduced species can threaten native species, such as cutthroat trout
      (Oncorhynchus clarkii) following the introduction of rainbow trout (O. mykiss).
      Neither the evolutionary consequences nor conservation implications of rainbow
      trout introgression in cutthroat trout is well understood. Therefore, we
      generated a genetic linkage map for rainbow-Yellowstone cutthroat trout (O.
      clarkii bouvieri) hybrids to evaluate genome processes that may help explain how
      introgression affects hybrid genome evolution. RESULTS: The hybrid map closely
      aligned with the rainbow trout map (a cutthroat trout map does not exist),
      sharing all but one linkage group. This linkage group (RYHyb20) represented a
      fusion between an acrocentric (Omy28) and a metacentric chromosome (Omy20) in
      rainbow trout. Additional mapping in Yellowstone cutthroat trout indicated the
      two rainbow trout homologues were fused in the Yellowstone genome. Variation in
      the number of hybrid linkage groups (28 or 29) likely depended on a Robertsonian
      rearrangement polymorphism within the rainbow trout stock. Comparison between the
      female-merged F1 map and a female consensus rainbow trout map revealed that
      introgression suppressed recombination across large genomic regions in 5 hybrid
      linkage groups. Two of these linkage groups (RYHyb20 and RYHyb25_29) contained
      confirmed chromosome rearrangements between rainbow and Yellowstone cutthroat
      trout indicating that rearrangements may suppress recombination. The frequency of
      allelic and genotypic segregation distortion varied among parents and families,
      suggesting few incompatibilities exist between rainbow and Yellowstone cutthroat
      trout genomes. CONCLUSIONS: Chromosome rearrangements suppressed recombination in
      the hybrids. This result supports several previous findings demonstrating that
      recombination suppression restricts gene flow between chromosomes that differ by
      arrangement. Conservation of synteny and map order between the hybrid and rainbow
      trout maps and minimal segregation distortion in the hybrids suggest rainbow and
      Yellowstone cutthroat trout genomes freely introgress across chromosomes with
      similar arrangement. Taken together, these results suggest that rearrangements
      impede introgression. Recombination suppression across rearrangements could
      enable large portions of non-recombined chromosomes to persist within admixed
      populations.

PMID- 23968235
TI  - TSAT is a better predictor than ferritin of hemoglobin response to Epoetin alfa
      in US dialysis patients.
AB  - Clinical guidelines recommend concurrent treatment of anemia in end-stage renal
      disease with erythropoiesis-stimulating agents (ESAs) and iron. However, there
      are mixed data about optimal iron supplementation. To help address this gap, the
      relationship between iron markers and hemoglobin (Hb) response to ESA (Epoetin
      alfa) dose was examined. Electronic medical records of 1902 US chronic
      hemodialysis patients were analyzed over a 12-month period between June 2009 and
      June 2010. The analysis included patients who had at least one Hb value during
      each 4-week interval for four consecutive intervals (k - 2, k - 1, k, and k + 1;
      k is the index interval), received at least one ESA dose during intervals k - 1
      or k, had at least one transferrin saturation (TSAT) value at interval k, and at
      least one ferritin value during intervals k - 2, k - 1, or k. Effect modification
      by TSAT and ferritin on Hb response was evaluated using the generalized
      estimating equations approach. Patients had a mean (standard deviation) age of 62
      (15) years; 41% were Caucasian, 34% African American, 65% had hypertension, and
      39% diabetes. Transferrin saturation, but not ferritin, had a statistically
      significant (P < 0.05) modifying effect on Hb response. Maximum Hb response was
      achieved when TSAT was 34%, with minimal incremental effect beyond these levels.
      Of the two standard clinical iron markers, TSAT should be used as the primary
      marker of the modifying effect of iron on Hb response to ESA. Long-term safety of
      iron use to improve Hb response to ESA warrants further study. 

PMID- 23968236
TI  - Rapid calculation of accurate atomic charges for proteins via the
      electronegativity equalization method.
AB  - We focused on the parametrization and evaluation of empirical models for fast and
      accurate calculation of conformationally dependent atomic charges in proteins.
      The models were based on the electronegativity equalization method (EEM), and the
      parametrization procedure was tailored to proteins. We used large protein
      fragments as reference structures and fitted the EEM model parameters using
      atomic charges computed by three population analyses (Mulliken, Natural,
      iterative Hirshfeld), at the Hartree-Fock level with two basis sets (6-31G*, 6
      31G**) and in two environments (gas phase, implicit solvation). We parametrized
      and successfully validated 24 EEM models. When tested on insulin and ubiquitin,
      all models reproduced quantum mechanics level charges well and were consistent
      with respect to population analysis and basis set. Specifically, the models
      showed on average a correlation of 0.961, RMSD 0.097 e, and average absolute
      error per atom 0.072 e. The EEM models can be used with the freely available EEM
      implementation EEM_SOLVER. 

PMID- 23968237
TI  - Association of physical activity and sedentary behavior with biological markers
      among U.S. pregnant women.
AB  - BACKGROUND: To examine the association between objectively measured light
      intensity and moderate-to-vigorous-intensity physical activity (MVPA), sedentary
      behaviors, and biological markers in a national sample of U.S. pregnant women, as
      few studies have examined these relationships among this population. METHODS: The
      sample of noninstitutionalized U.S. civilians was selected by a complex,
      multistage probability design. Data from the 2003-2006 National Health and
      Examination Survey were used. Two hundred six pregnant women were included in the
      data analysis. Physical activity and sedentary data were objectively measured via
      accelerometry (ActiGraph 7164). Biomarker data was obtained in the mobile
      examination center from urine, blood samples, blood pressure, and anthropometric
      measurements. Urine and blood samples were obtained to determine pregnancy
      status, C-reactive protein (CRP), high-density lipoprotein (HDL) cholesterol,
      total cholesterol, and cotinine as well as fasting glucose, fasting
      triglycerides, and fasting low-density lipoprotein (LDL) cholesterol data.
      Multivariable regression was employed to examine the association between physical
      activity, sedentary behavior, and biomarker levels. RESULTS: There was a positive
      association between sedentary behavior and CRP levels (beta coefficient
      [b]=0.001, p=0.02) and LDL cholesterol (b=0.12, p=0.02). There was an inverse
      association between light-intensity physical activity and CRP (b=-0.003; p=0.008)
      and diastolic blood pressure (b=-0.03; p=0.02), with those engaging in higher
      levels of MVPA having higher HDL cholesterol (b=6.7; p=0.01). CONCLUSION:
      Physical activity and sedentary behavior were favorably associated with various
      biomarkers among pregnant women, suggesting that healthcare providers should
      encourage pregnant women to participate in safe forms of physical activity
      behaviors while also reducing their amount of time spent in sedentary behaviors.

PMID- 23968238
TI  - Locomotor control in the long jump approach run in young novice athletes.
AB  - We examine the presence of visually regulated control in young, novice long
      jumpers as they approach the takeoff board. The approach run of 27 novice jumpers
      (age 12-13 years) practising jump training for a short period was video-recorded
      during competition. Findings revealed that young, novice participants adjust the
      length of the final steps of their approach run, suggesting the presence of
      visual control. Step regulation commenced on the fifth and fourth step from the
      board for boys and girls respectively. Their pattern of footfall variability was
      found to be comparable to that of skilled long jumpers, although young, novice
      participants presented slightly higher variability. It appears that even a
      limited period of jump training may contribute to a more consistent run-up as
      well as to smaller takeoff error, offsetting the limitations imposed by the
      partially developed cognitive abilities and perceptual awareness of young
      athletes.

PMID- 23968239
TI  - Effective osteoporosis treatment with teriparatide is associated with enhanced
      quality of life in postmenopausal women with osteoporosis: the European Forsteo
      Observational Study.
AB  - BACKGROUND: To describe changes in health-related quality of life (HRQoL) of
      postmenopausal women with osteoporosis treated with teriparatide for up to 18
      months and followed-up for a further 18 months, and to assess the influence of
      recent prior and incident fractures. METHODS: The European Forsteo Observational
      Study (EFOS) is an observational, prospective, multinational study measuring
      HRQoL using the EQ-5D. The primary objective was to assess changes in HRQoL
      during 36 months in the whole study population. A secondary post-hoc analysis
      examined fracture impact on HRQoL in four subgroups classified based on recent
      prior fracture 12 months before baseline and incident clinical fractures during
      the study. Changes from baseline were analysed using a repeated measures model.
      RESULTS: Of the 1581 patients, 48.4% had a recent prior fracture and 15.6% of
      these patients had an incident fracture during follow-up. 10.9% of the 816
      patients with no recent prior fracture had an incident fracture. Baseline mean EQ
      VAS scores were similar across the subgroups. In the total study cohort (n =
      1581), HRQoL (EQ-VAS and EQ-5D index scores) improved significantly from baseline
      to 18 months and this improvement was maintained over the 18-month post
      teriparatide period. Improvements were seen across all five EQ-5D domains during
      teriparatide treatment that were maintained after teriparatide was discontinued.
      Subjects with incident clinical fractures had significantly less improvement in
      EQ-VAS than those without incident fractures. Recent prior fracture did not
      influence the change in EQ-VAS during treatment. CONCLUSIONS: EFOS is the first
      longitudinal study in women with severe postmenopausal osteoporosis in the real
      world setting to show a substantial improvement in HRQoL during teriparatide
      treatment that was sustained during subsequent treatment with other medications.
      The increase in HRQoL was lower in the subgroups with incident fracture but was
      not influenced by recent prior fracture. The results should be interpreted in the
      context of the design of an observational study.

PMID- 23968240
TI  - Eccrine poromatosis: case report and review of the literature.
AB  - Eccrine poroma (EP) is a benign tumor of the eccrine duct. Multiple EPs are
      defined as eccrine poromatosis (EPS), an uncommon phenomenon. To date there are
      only eight reported cases of EPS. This review exemplifies the epidemiology,
      pathogenesis, differential diagnosis, and histology of EP, while reviewing the
      eight cases of EPS. Six of the eight cases of EPS had a history of
      immunosuppression from either radiation or chemotherapy. This paper will also
      emphasize the importance of excision to avoid possible malignancy. Here we
      present a 73-year-old gentleman with EPS who was also treated with radiation and
      chemotherapy prior to the onset of the lesions. 

PMID- 23968242
TI  - Porating anion-responsive copolymeric gels.
AB  - A polymerizable ionic liquid surfactant, 1-(11-acryloyloxyundecyl)-3
      methylimidiazolium bromide (ILBr), was copolymerized with methyl methacrylate
      (MMA) in aqueous microemulsions at 30% (ILBr w/w) and various water to MMA
      ratios. The ternary phase diagram of the ILBr/MMA/water system was constructed at
      25 and 60  degrees C. Homopolymers and copolymers of ILBr and MMA were produced
      by thermally initiated chain radical microemulsion polymerization at various
      compositions in bicontinuous and reverse microemulsion subdomains. Microemulsion
      polymerization reaction products varied from being gel-like to solid, and these
      materials were analyzed by thermal and scanning electron microscopy methods.
      Microemulsion polymerized materials were insoluble in all solvents tested,
      consistent with light cross-linking. Ion exchange between Br(-) and PF6(-) in
      these copolymeric materials resulted in the formation of open-cell porous
      structures in some of these materials, as was confirmed by scanning electron
      microscopy (SEM). Several compositions illustrate the capture of
      prepolymerization nanoscale structure by thermally initiated polymerization,
      expanding the domain of compositions exhibiting this feat and yet to be
      demonstrated in any other system. Regular cylindrical pores in interpenetrating
      ILBr-co-MMA and PMMA networks are produced by anion exchange in the absence of
      templates. A percolating cluster/bicontinuous transition is "captured" by SEM
      after using anion exchange to visualize the mixed cluster/pore morphology. Some
      design principles for achieving this capture and for obtaining stimuli responsive
      solvogels are articulated, and the importance of producing solvogels in capturing
      the nanoscale is highlighted. 

PMID- 23968243
TI  - Low-grade intraventricular hemorrhage: is ultrasound good enough?
AB  - OBJECTIVE: To assess diagnostic accuracy of cranial ultrasonography (CUS) in
      detecting low-grade (i.e. grade I and grade II) germinal matrix hemorrhage
      intraventricular hemorrhage (GMH-IVH) in very low birth weight (VLBW) infants.
      METHODS: Among VLBW infants who were admitted to Gaslini Children's Hospital
      neonatal intensive care unit between January and November 2012, patients who
      underwent both serial CUS since birth and magnetic resonance susceptibility
      weighted imaging (SWI) at term-equivalent age were included in this retrospective
      study. Diagnostic accuracy of CUS in detecting low-grade GMH-IVH was assessed in
      terms of sensitivity and specificity by comparing it to SWI, which was used as
      the gold-standard technique. RESULTS: Sixty VLBW infants were included in the
      study. Sensitivity of CUS in detecting low-grade GMH-IVH was low (60%), whilst
      specificity was 100%. CONCLUSIONS: In the present study, CUS sensitivity in
      detecting grade I-II GMH-IVH proved to be surprisingly low, in contrast with
      specificity. In other words, we suggest that low-grade GMH-IVH may be
      underdiagnosed in VLBW infants when assessed exclusively with CUS.

PMID- 23968244
TI  - The use of botulinum toxin-A in the management of neck and anterior chest wall
      flushing: pilot study.
AB  - Idiopathic neck and chest wall flushing could cause disabling effects on
      patients' quality of life. We aimed to evaluate the effectiveness of botulinum
      toxin-A (BTA) in the management of idiopathic neck and chest wall flushing. This
      was a pilot prospective clinical study of patients with severe idiopathic neck
      and anterior chest wall flushing. Two mouse units of BTA were injected
      intracutaneously with a maximum dose of 100 units per patient per session. The
      dermatology life quality index is used as the primary outcome measure. Twenty-two
      patients were included in the study (18 women, four men) with an average age of
      26 years (range 18-48). Twenty patients (90.9%) had immediate improvement with
      almost complete resolution of their flushing. At four weeks follow-up, 18 of 22
      patients were included in the final analysis, significant improvement in quality
      of life was achieved, and mean baseline dermatology life quality index score 7.78
      (SD 3.25) improved significantly to 4.23 (SD 3.44) with a mean difference of 3.56
      (SD 4.6; 95%, confidence interval 1.27, 5.84) with paired samples t-test 3.29
      (d.f. 17) P < 0.004. BTA may provide an effective treatment in the management of
      idiopathic neck and chest wall flushing.

PMID- 23968245
TI  - Genetics of milking characteristics in dairy cows.
AB  - Genetic selection for milking speed is feasible. The existence of a correlation
      structure between milking speed and milk yield, however, necessitates a selection
      strategy to increase milking speed with no repercussion on genetic merit for milk
      yield. Residual milking duration (RMD) and residual milking duration including
      somatic cell score (RMDS), defined as the residuals from a regression model of
      milking duration on milk yield or milk yield plus somatic cell score (SCS) have
      been advocated. The objective of this study was to undertake a first ever genetic
      analysis of these novel traits. Data on electronically recorded milking duration
      and other milking characteristics from 235 005 test-day records on 74 608 cows in
      1075 Irish dairy herds were available. Variance components for the milking
      characteristic traits were estimated using animal linear mixed models and
      covariances with other performance traits, including udder-related type traits,
      were estimated using sire models. The heritability of milking duration, RMD and
      RMDS was 0.20, 0.22 and 0.18, respectively. There were little differences in the
      heritability of RMD or RMDS when defined using genetic regression. The genetic
      standard deviation of RMDS defined on the phenotypic or genetic level was 36.8 s
      and 37.6 s, respectively, clearly indicating considerable exploitable genetic
      variation in milking duration independent of both milk yield and SCS. The genetic
      correlation between phenotypically derived RMDS and milk yield was favourable (
      0.43), but RMDS was unfavourably genetically correlated with SCS (-0.30); the
      genetic correlations with both traits when RMDS was defined at a genetic level
      were zero. RMDS defined at the phenotypic level was negatively (i.e.
      unfavourable) genetically correlated (-0.35; s.e. = 0.15) with mastitis; however,
      when defined using genetic regression, shorter RMDS was not associated with
      greater expected incidence of mastitis. RMDS, defined at the genetic level, is a
      useful heritable trait with ample genetic variation for inclusion in a national
      breeding strategy without influencing genetic gain in either milk yield or udder
      health. 

PMID- 23968241
TI  - Pharmacotherapy of traumatic brain injury: state of the science and the road
      forward: report of the Department of Defense Neurotrauma Pharmacology Workgroup.
AB  - Despite substantial investments by government, philanthropic, and commercial
      sources over the past several decades, traumatic brain injury (TBI) remains an
      unmet medical need and a major source of disability and mortality in both
      developed and developing societies. The U.S. Department of Defense neurotrauma
      research portfolio contains more than 500 research projects funded at more than
      $700 million and is aimed at developing interventions that mitigate the effects
      of trauma to the nervous system and lead to improved quality of life outcomes. A
      key area of this portfolio focuses on the need for effective pharmacological
      approaches for treating patients with TBI and its associated symptoms. The
      Neurotrauma Pharmacology Workgroup was established by the U.S. Army Medical
      Research and Materiel Command (USAMRMC) with the overarching goal of providing a
      strategic research plan for developing pharmacological treatments that improve
      clinical outcomes after TBI. To inform this plan, the Workgroup (a) assessed the
      current state of the science and ongoing research and (b) identified research
      gaps to inform future development of research priorities for the neurotrauma
      research portfolio. The Workgroup identified the six most critical research
      priority areas in the field of pharmacological treatment for persons with TBI.
      The priority areas represent parallel efforts needed to advance clinical care;
      each requires independent effort and sufficient investment. These priority areas
      will help the USAMRMC and other funding agencies strategically guide their
      research portfolios to ensure the development of effective pharmacological
      approaches for treating patients with TBI.

PMID- 23968246
TI  - The influence of dopamine-related genes on perceptual stability.
AB  - Bistable perception is the spontaneous and automatic alternation between two
      different perceptual states that occurs when sensory information is ambiguous.
      Perceptual alternation rates are robust within individuals but vary substantially
      between individuals. Slowed perceptual switching has been consistently reported
      in patients with bipolar disorder (BPD) and has been suggested as a trait marker
      for this disease. Although genetic factors have been implicated in both BPD and
      bistable perception, the underlying biological mechanisms that mediate the
      observed perceptual stability in BPD remain elusive. Here, we tested the effect
      of two variable number tandem repeat (VNTR) polymorphisms in DRD4 and DAT1
      (SLC6A3), both candidate genes for BPD with functional impact on dopaminergic
      neurotransmission, on bistable perception in a cohort of 108 healthy human
      subjects. The BPD risk allele DRD4-2R was significantly associated with slow
      perceptual switching. There was no effect of DAT1 genotype on bistable
      perception. Our findings indicate that genetic differences in dopaminergic
      neurotransmission linked to BPD also account for interindividual variability in
      bistable perception, thus providing a genetic basis for perceptual stability as a
      trait marker of BPD.

PMID- 23968247
TI  - Lesions caused by Africanized honeybee stings in three cattle in Brazil.
AB  - We report three cases of stings by Africanized bees in cattle in the state of Rio
      de Janeiro, Brazil. Erythema, subcutaneous edema, necrosis accompanied by skin
      detachment, and subsequent skin regeneration were observed, especially on the
      head and dewlap. Histopathological examinations performed 45 days later revealed
      complete skin reepithelialization with moderate dermal fibrosis. The clinical
      picture and differential diagnosis are discussed in the present manuscript, with
      a focus on photosensitization, which causes cutaneous lesions on the head
      (sequela) with cicatricial curving of the ears and can be very similar to what is
      observed in cattle attacked by swarms of bees. The distinction between
      photosensitization and bee sting lesions can be made with a focus on history and
      clinical and pathological aspects. 

PMID- 23968248
TI  - Whole transcriptome RNA-Seq allelic expression in human brain.
AB  - BACKGROUND: Measuring allelic RNA expression ratios is a powerful approach for
      detecting cis-acting regulatory variants, RNA editing, loss of heterozygosity in
      cancer, copy number variation, and allele-specific epigenetic gene silencing.
      Whole transcriptome RNA sequencing (RNA-Seq) has emerged as a genome-wide tool
      for identifying allelic expression imbalance (AEI), but numerous factors bias
      allelic RNA ratio measurements. Here, we compare RNA-Seq allelic ratios measured
      in nine different human brain regions with a highly sensitive and accurate
      SNaPshot measure of allelic RNA ratios, identifying factors affecting reliable
      allelic ratio measurement. Accounting for these factors, we subsequently surveyed
      the variability of RNA editing across brain regions and across individuals.
      RESULTS: We find that RNA-Seq allelic ratios from standard alignment methods
      correlate poorly with SNaPshot, but applying alternative alignment strategies and
      correcting for observed biases significantly improves correlations. Deploying
      these methods on a transcriptome-wide basis in nine brain regions from a single
      individual, we identified genes with AEI across all regions (SLC1A3, NHP2L1) and
      many others with region-specific AEI. In dorsolateral prefrontal cortex (DLPFC)
      tissues from 14 individuals, we found evidence for frequent regulatory variants
      affecting RNA expression in tens to hundreds of genes, depending on stringency
      for assigning AEI. Further, we find that the extent and variability of RNA
      editing is similar across brain regions and across individuals. CONCLUSIONS:
      These results identify critical factors affecting allelic ratios measured by RNA
      Seq and provide a foundation for using this technology to screen allelic RNA
      expression on a transcriptome-wide basis. Using this technology as a screening
      tool reveals tens to hundreds of genes harboring frequent functional variants
      affecting RNA expression in the human brain. With respect to RNA editing, the
      similarities within and between individuals leads us to conclude that this post
      transcriptional process is under heavy regulatory influence to maintain an
      optimal degree of editing for normal biological function.

PMID- 23968250
TI  - Comment on: Boris bikes--an accident waiting to happen?

PMID- 23968251
TI  - Combined laparoscopic and hysteroscopic approach for the treatment of a hybrid
      Mullerian duct anomaly: a case report.
AB  - Mullerian duct anomalies include a wide spectrum of genital tract defects
      resulting from a development alteration of the genital tract. An 11-year-old girl
      with a hybrid septate variety uterus with left hemi-obstruction was identified.
      Beside preoperative imaging evaluation done with ultrasound, magnetic resonance,
      and hysterosalpingography, a combined laparoscopic and hysteroscopic procedure
      was fundamental for the diagnosis. The surgical procedure also allowed us to
      perform a successful and safe treatment. We propose that the American Fertility
      Society classification of these anomalies should be revised and that hybrid
      entities should be considered in the differential diagnosis of genital tract
      malformations.

PMID- 23968249
TI  - Combination therapy using Pentostam and Praziquantel improves lesion healing and
      parasite resolution in BALB/c mice co-infected with Leishmania major and
      Schistosoma mansoni.
AB  - BACKGROUND: Most natural host populations are exposed to a diversity of parasite
      communities and co-infection of hosts by multiple parasites is commonplace across
      a diverse range of systems. Co-infection with Leishmania major and Schistosoma
      mansoni may have important consequences for disease development, severity and
      transmission dynamics. Pentavalent antimonials and Praziquantel (PZQ) have been
      relied upon as a first line of treatment for Leishmania and Schistosoma
      infections respectively. However, it is not clear how combined therapy with the
      standard drugs will affect the host and parasite burden in concomitance. The aim
      of the current study was to determine the efficacy of combined chemotherapy using
      Pentostam and PZQ in BALB/c mice co-infected with L. major and S. mansoni.
      METHODS: The study used BALB/c mice infected with L. major and S. mansoni. A 3 *
      4 factorial design with three parasite infection groups (Lm, Sm, Lm + Sm
      designated as groups infected with L. major, S. mansoni and L. major + S.
      mansoni, respectively) and four treatment regimens [P, PZQ, P + PZQ and PBS
      designating Pentostam(r)(GlaxoSmithKline UK), Praziquantel (Biltricide(r), Bayer
      Ag. Leverkusen, Germany), Pentostam + Praziquantel and Phosphate buffered saline]
      as factors was applied. In each treatment group, there were 10 mice. Lesion
      development was monitored for 10 weeks. The parasite load, body weight, weight of
      the spleen and liver were determined between week 8 and week 10. RESULTS:
      Chemotherapy using the first line of treatment for L. major and S. mansoni
      reduced the lesion size and parasite loads but did not affect the growth
      response, spleen and liver. In the co-infected BALB/c mice, the use of Pentostam
      or PZQ did not result in any appreciable disease management. However, treatment
      with P + PZQ resulted in significantly (p < 0.05) larger reduction of lesions,
      net increase in the body weight, no changes in the spleen and liver weight and
      reduced Leishman-Donovan Units (LDU) and worm counts than BALB/c mice treated
      with Pentostam or PZQ alone. CONCLUSIONS: The present study demonstrated that the
      combined first line of treatment is a more effective strategy in managing co
      infection of L. major and S. mansoni in BALB/c mice.

PMID- 23968252
TI  - Laparoscopic methods in the treatment of congenital duodenal obstruction for
      neonates.
AB  - OBJECTIVE: To evaluate the feasibility of and indication for laparoscopic methods
      for neonates with congenital duodenal obstruction. PATIENTS AND METHODS: From
      September 2009 to October 2012, 40 newborns with duodenal obstruction underwent
      exploratory laparoscopy. With a lower-pressure pneumoperitoneum of 6-8 mm Hg and
      a suspending suture for the right liver elevator, the procedure was performed
      using four trocars 3-5 mm in diameter. Under laparoscopic vision, the causes of
      duodenal obstruction were diagnosed, and then the operation methods were
      determined by the type of obstruction. RESULTS: Of the 40 cases, 4 were duodenal
      atresia (type II), 8 were duodenal stenosis, 8 were annular pancreas, and 20 were
      congenital intestinal malrotation. For the cases with duodenal diaphragmatic
      stenosis a partial excision of the diaphragm was performed after longitudinal
      incision of the anterior part of the duodenum followed laparoscopically by a
      transverse suture. For the cases with duodenal atresia (type II) and annular
      pancreas, a duodenal diamond anastomosis was successfully carried out through a
      laparoscopic approach. Ladd's operational method was performed in the cases with
      congenital intestinal malrotation. Feedings were started on postoperative Day 3
      7, without abdominal distention and vomiting, and discharge from the the hospital
      was on postoperative Day 9-14. CONCLUSIONS: Congenital duodenal obstruction is a
      common malformation in neonates. The laparoscopic procedure is an important
      method of diagnosing, and correct operational methods are the key to improve the
      therapeutic effect in the treatment of congenital duodenal obstruction. The
      laparoscope has the value of a small incision, microinvasion, and better recovery
      in diagnosis and treatment for congenital duodenal obstruction. The laparoscopic
      methods can be performed in neonates safely and are appropriate for a full-term
      newborn with tolerance to CO2 pneumoperitoneum.

PMID- 23968253
TI  - Laparoscopic gastrectomy for gastric cancer with simultaneous organ resection.
AB  - OBJECTIVES: Simultaneous organ resection is performed in 10% of laparoscopic
      gastrectomies for gastric cancer. The purpose of this study is to investigate the
      feasibility and safety of simultaneous organ resection with laparoscopic
      gastrectomy for gastric cancer. SUBJECTS AND METHODS: We retrospectively reviewed
      the medical records from a prospectively collected database of patients who
      underwent laparoscopic gastrectomy from May 2003 to April 2012 in a single
      center. The patients were classified into three groups: a gastrectomy-only (no
      simultaneous resection [NS]) group as a control, a combined resection (CB) group
      characterized by additional resection due to tumor invasion and extensive
      lymphadenectomy, and a concomitant resection (CC) group, including patients with
      other pathologic conditions. The clinical outcomes, in particular morbidity and
      mortality, were compared among the three groups. RESULTS: The NS, CB, and CC
      groups included 1883 (90.1%), 66 (3.2%), and 140 (6.7%) patients, respectively.
      Mean operation time was longer in CB and CC patients than in NS patients (233.0
      +/- 59.3, 227.4 +/- 100.9, and 180.1 +/- 54.0 minutes, respectively; P<.001), and
      mean hospital stay was longer in the CB and CC groups than in the NS group (9.6
      +/- 5.2, 8.3 +/- 4.7, and 6.9 +/- 4.4 days, respectively; P<.001). However, there
      were no statistically significant differences among the groups in the incidence
      of complications (P=.185), complications more severe than grade II (P=.077), and
      mortality (P=1.000). CONCLUSIONS: Laparoscopic simultaneous organ resection
      during laparoscopic gastrectomy for gastric cancer prolonged the operation time
      and hospital stay but did not increase morbidity and mortality.

PMID- 23968254
TI  - Laparoscopic transhiatal esophagectomy and gastric pull-up in long-gap esophageal
      atresia: description of the technique in our first 10 cases.
AB  - The definition accepted for the largely controversial and multiple criteria
      condition known as long-gap esophageal atresia (LGEA) is "inability to achieve
      primary end-to-end anastomosis," particularly in the presence of a tracheo
      esophageal fistula. In this article we report our technique of laparoscopic
      transhiatal esophagectomy and gastric pull-up (TEGPUL) in LGEA, based on the open
      approach of Spitz. Differences between TEGPUL and the original technique are the
      absence of a pyloromyotomy, the peel-away technique, the gastric pull-up through
      the distal esophagus, and its extracorporeal section. We performed the technique
      in 10 patients: 6 girls and 4 boys. Six had esophageal atresia type III (60%),
      three had esophageal atresia type I (30%) and one had esophageal atresia type II
      (10%). Mean time in surgery was 4.43 hours (range, 3.3-7 hours). Average stay in
      the pediatric intensive care unit was 5.9 days (range, 3-25 days). Average time
      under mechanical ventilation was 4.6 days (range, 2-8 days). Average total
      hospital stay was 19.4 days (range, 11-40 days). Oral feeding began at 15.6 days
      (range, 5-30 days). We believe these steps and the early realization of the
      technique will reduce the morbidity and mortality among these patients and
      decrease the number of contraindications to gastric pull-up. Nevertheless, a
      valid conclusion will require more studies with a larger number of patients and
      longer follow-up.

PMID- 23968255
TI  - Construct, concurrent, and content validity of the eoSim laparoscopic simulator.
AB  - BACKGROUND: The purpose of this study was to validate the eoSim box laparoscopic
      simulator using measures of construct, concurrent, and content validity. SUBJECTS
      AND METHODS: Forty-seven novice and expert participants were tested on both the
      Fundamentals of Laparoscopic Surgery (FLSTM; Society of American Gastrointestinal
      and Endoscopic Surgeons, Los Angles, CA) and eoSim (eoSurgicalTM, Edinburgh,
      Scotland, United Kingdom) laparoscopic simulators, using established scoring
      mechanisms. Three skill areas were examined: object transfer, precision cutting,
      and intracorporeal suturing. A questionnaire was also completed. RESULTS: Experts
      performed significantly better on the eoSim than novices, with a median score of
      51.1% versus 14.8% (P<.0001), showing construct validity. There was a high
      correlation between performance on the validated FLS simulator and the eoSim
      (0.78; P<.0001), demonstrating concurrent validity. Feedback from participants
      indicated an agreement that the eoSim was a useful training tool providing
      content validity. CONCLUSIONS: The eoSim demonstrates validity as a model for
      laparoscopic simulation. It is hoped that its decreased cost relative to other
      simulators will encourage increased uptake by trainees and institutions.

PMID- 23968256
TI  - Understanding the role of aqueous solution speciation and its application to the
      directed syntheses of complex oxidic Zr chlorides and sulfates.
AB  - The lack of an in-depth understanding of solution-phase speciation and its
      relationship to solid-state phase formation is a grand challenge in synthesis
      science. It has severely limited the ability of inorganic chemists to predict or
      rationalize the formation of compounds from solutions. The need to investigate
      mechanisms that underlie self-assembly has motivated this study of aqueous Zr
      sulfate chemistry as a model system, with the goal of understanding the
      structures of oligomeric clusters present in solution. We used high-energy X-ray
      scattering (HEXS) data to quantify Zr correlations in a series of solutions as a
      function of sulfate concentration. The pair distribution function (PDF) from the
      sulfate-free sample reveals that the average oligomeric Zr moiety is larger than
      the tetrameric building unit, [Zr4(OH)8(H2O)16](8+), generally understood to
      dominate its solution speciation. At sulfate concentrations greater than 1 m
      (molal), bidentate sulfate is observed, a coordination not seen in Zr(SO4)2.4H2O
      (2), which forms upon evaporation. Also seen in solution are correlations
      consistent with sulfate-bridged Zr dimers and the higher-order oligomers seen in
      2. At intermediate sulfate concentrations there are correlations consistent with
      large Zr hydroxo-/oxo-bridged clusters. Crystals of
      [Zr18(OH)26O20(H2O)23.2(SO4)12.7]Cl0.6.nH2O (3) precipitate from these solutions.
      The Raman spectrum of 3 has a peak at 1017 cm(-1) that can be used as a signature
      for its presence in solution. Raman studies on deuterated solutions point to the
      important role of sulfate in the crystallization process. These solution results
      emphasize the presence of well-defined prenucleation correlations on length
      scales of <1 nm, often considered to be within the structurally amorphous regime.

PMID- 23968257
TI  - Sand training: a review of current research and practical applications.
AB  - Sand surfaces can offer a higher energy cost (EC) and lower impact training
      stimulus compared with firmer and more traditional team sport training venues
      such as grass. This review aims to summarise the existing research on sand
      training, with a specific focus on its application as a team sports training
      venue. Compared with grass, significant physiological and biomechanical
      differences are associated with sand exercise. However, evidence also exists to
      suggest that training adaptations unique to sand can positively influence firm
      ground performance. Furthermore, the lower impact forces experienced on sand can
      limit muscle damage, muscle soreness, and decrements in performance capacity
      relative to exercise intensity. Therefore, using a sand training surface in team
      sports may allow greater training adaptations to be achieved, while reducing
      performance decrements and injuries that may arise from heavy training.
      Nevertheless, further research should investigate the effect of sand surfaces
      over a greater range of training types and performance outcomes, to increase the
      application of sand training for team sports.

PMID- 23968258
TI  - Different kinetic pathways of early stage calcium-phosphate cluster aggregation
      induced by carboxylate-containing polymers.
AB  - Acidic proteins are critical to biomineral formation, although their precise
      mechanistic function remains poorly understood. A number of recent studies have
      suggested a nonclassical mineralization model that emphasizes the importance of
      the formation of polymer-stabilized mineral clusters or particles; however, it
      has been difficult to characterize the precursors experimentally due to their
      transient nature. Here, we successfully captured stepwise evolution of transient
      CaP clusters in mineralizing solutions and studied the roles of functional
      polymers with laser light scattering (LLS) to determine how these polymers
      influence the stability of nanoclusters. We found that the polymer structure can
      alter CaP aggregation mechanisms, whereas the polymer concentration strongly
      influences the rate of CaP aggregation. Our results indicate that the ability of
      acidic biomolecules to control the formation of relatively stable nanoclusters in
      the early stages may be critical for intrafibrillar mineralization. More
      importantly, LLS provided information about the size and the structural evolution
      of CaP aggregates, which will help define the process of controlled
      biomineralization. 

PMID- 23968259
TI  - Quantifying the fingerprint descriptor dependence of structure-activity
      relationship information on a large scale.
AB  - It is well-known that different molecular representations, e.g., graphs,
      numerical descriptors, fingerprints, or 3D models, change the numerical results
      of molecular similarity calculations. Because the assessment of structure
      activity relationships (SARs) requires similarity and potency comparisons of
      active compounds, this representation dependence inevitably also affects SAR
      analysis. But to what extent? How exactly does SAR information change when
      alternative fingerprints are used as descriptors? What is the proportion of
      active compounds with substantial changes in SAR information induced by different
      fingerprints? To provide answers to these questions, we have quantified changes
      in SAR information across many different compound classes using six different
      fingerprints. SAR profiling was carried out on 128 target-based data sets
      comprising more than 60,000 compounds with high-confidence activity annotations.
      A numerical measure of SAR discontinuity was applied to assess SAR information on
      a per compound basis. For ~70% of all test compounds, changes in SAR
      characteristics were detected when different fingerprints were used as molecular
      representations. Moreover, the SAR phenotype of ~30% of the compounds changed,
      and distinct fingerprint-dependent local SAR environments were detected. The
      fingerprints we compared were found to generate SAR models that were essentially
      not comparable. Atom environment and pharmacophore fingerprints produced the
      largest differences in compound-associated SAR information. Taken together, the
      results of our systematic analysis reveal larger fingerprint-dependent changes in
      compound-associated SAR information than would have been anticipated.

PMID- 23968260
TI  - Microstructure of titanium-cement-lithium disilicate interface in CAD-CAM dental
      implant crowns: a three-dimensional profilometric analysis.
AB  - BACKGROUND: Peri-implantitis is an infection of the implant surface caused by
      adhesion of bacteria that generate bone resorption and sometimes even consequent
      implant loss. Both screw-retained and cemented fixed implants are affected.
      PURPOSE: The purpose of this study is to investigate the morphological defects at
      the cemented interface between titanium abutment and ceramic crown, comparing
      different adhesive cements used to fill the marginal gap. MATERIALS AND METHODS:
      Twelve computer-aided design-computer-aided manufacturing dental crowns were
      cemented to titanium abutments using three different resin composite cements.
      Sealed margins were polished using grommets with descending diamond particle
      size. Three groups of four crowns each were made according to the cement used,
      namely RelyX Unicem (3 M ESPE), Panavia F 2.0 (Kuraray), and NX3 (Nexus Kerr).
      Samples were analyzed using optical inspection, three-dimensional profilometry,
      and image analysis, including analysis of variance. RESULTS: Although RelyX
      showed significantly lower root mean square surface roughness (4.4 +/- 1.5 MUm)
      than that of NX3 (7.0 +/- 2.9 MUm), it showed no significant difference with
      Panavia (3.7 +/- 1.5 MUm). The marginal gap was significantly wider in Panavia
      (149 +/- 108 MUm) as compared with NX3 (71 +/- 45 MUm) and Relyx (64 +/- 34 MUm).
      For all groups, homogeneous heights of both metal-cement and ceramic-cement gaps
      were observed. Moreover, all samples showed homogeneity of the margins and
      absence of instrumental bias, thus validating both procedure and materials.
      CONCLUSIONS: When using the chosen polishing method, RelyX Unicem showed both low
      roughness and marginal width, and thus the smoothest and more continuous abutment
      crown interlayer, promising a low probability of occurrence of peri-implantitis.

PMID- 23968261
TI  - Implementation of adaptive radiation therapy for urinary bladder carcinoma:
      imaging, planning and image guidance.
AB  - BACKGROUND: Adaptive radiation therapy (ART) for urinary bladder cancer has
      emerged as a promising alternative to conventional RT with potential to minimize
      radiation-induced toxicity to healthy tissues. In this work we have studied
      bladder volume variations and their effect on healthy bladder dose sparing and
      intrafractional margins, in order to refine our ART strategy. MATERIAL AND
      METHODS: An online ART treatment strategy was followed for five patients with
      urinary bladder cancer with the tumors demarcated using Lipiodol((r)). A library
      of 3-4 predefined treatment plans for each patient was created based on four
      successive computed tomography (CT) scans. Cone beam CT (CBCT) images were
      acquired before each treatment fraction and after the treatment at least weekly.
      In partial bladder treatment the sparing of the healthy part of the bladder was
      investigated. The bladder wall displacements due to bladder filling were
      determined in three orthogonal directions (CC, AP, DEX-SIN) using the treatment
      planning CT scans. An ellipsoidal model was applied in order to find the
      theoretical maximum values for the bladder wall displacements. Moreover, the
      actual bladder filling rate during treatment was evaluated using the CBCT images.
      Results. In partial bladder treatment the volume of the bladder receiving high
      absorbed doses was generally smaller with a full than empty bladder. The
      estimation of the bladder volume and the upper limit for the intrafractional
      movement of the bladder wall could be represented with an ellipsoidal model with
      a reasonable accuracy. Observed maximum growth of bladder dimensions was less
      than 10 mm in all three orthogonal directions during 15 minute interval.
      CONCLUSION: The use of Lipiodol contrast agent enables partial bladder treatment
      with reduced irradiation of the healthy bladder volume. The ellipsoidal bladder
      model can be used for the estimation of the bladder volume changes and the upper
      limit of the bladder wall movement during the treatment fraction.

PMID- 23968262
TI  - Healthcare quality and the public understanding of health.

PMID- 23968263
TI  - Variability in thyroid function test requests across general practices in south
      west England.
AB  - BACKGROUND: The number of thyroid function tests (TFTs) performed in the UK and
      other countries has increased considerably in recent years. Inconsistent clinical
      practice associated with inappropriate requests for tests is thought to be an
      important cause for this increase. AIM: To study the extent of variability in
      requests for TFTs from general practices. METHODS: We analysed routine data on
      all TFTs on patients aged 16 years and over carried out by two hospitals in south
      west England (Royal Cornwall Hospital and Royal Devon & Exeter Hospital) during
      2010 at the request of 107 general practices. RESULTS: A total of 195 309 TFT
      requests were made for 148 412 patients (63% female). The total requests included
      192 108 tests for thyroid-stimulating hormone (TSH), 43 069 for free thyroxine
      (FT4) and 1972 for free tri-iodothyronine (FT3). The number of TSH tests per 1000
      list size varied widely across the practices, ranging from 84 to 482. Most of the
      variation was due to heterogeneity across practices and only 24% of this was
      accounted for by prevalence of hypothyroidism and socio-economic deprivation.
      CONCLUSIONS: There is wide variation in TFT requests from general practice and
      scope to reduce both unnecessary TFTs and the variability in the clinical
      practice. Further studies are required to understand the causes for the
      variability in testing thyroid function.

PMID- 23968264
TI  - Care pathways to improve care co-ordination and quality between primary and
      hospital care for patients with radical prostatectomy: a quality improvement
      project.
AB  - BACKGROUND: Care pathways are widely used in hospitals to improve quality. There
      is a growing interest in extending care pathways into primary care. There is
      little evidence on the relationship between care pathways across the primary
      hospital care continuum and improvement in quality of care. Members of primary
      and hospital care services in the region of Bruges (Belgium) developed a care
      pathway for radical prostatectomy patients. An evaluation of this care pathway
      encountered some problems. AIM: To assess if a revision of the care pathway would
      improve quality of care enhancing patient outcomes. METHODS: An exploratory trial
      was performed to test the feasibility of quality measurement, the possible
      intervention effect and recruitment. A pre-post-intervention postal survey was
      used. Quality of care was translated into process and outcome indicators. These
      indicators were measured in two groups receiving a postal questionnaire: one
      group before (pre-intervention) and another group after implementation (post
      intervention). A Fisher's exact test was used to compare differences for
      dichotomous variables, and a Mann-Whitney U-test to compare ordinal and
      continuous variables. RESULTS: Observed improvements in process and outcome
      indicators were not statistically significant after correcting for multiple
      testing: 95.1% of patients received the information pack during the pre-operative
      consultation (versus 81.0% in the pre-intervention), 86.0% of the patients
      consulted a physiotherapist who specialised in pelvic floor muscle exercise
      treatment (versus 56.0% in the pre-intervention) and no patients experienced pain
      (versus 13.6% in the pre-intervention). No changes were observed for
      communication and co-ordination between caregivers. CONCLUSION: Given the
      background of scarce evidence on the quality improvement effect of care pathways
      between primary and hospital care, this exploratory trial provides information
      about the quality measurement, the possible intervention effect and recruitment.
      The quality improvement process is continuing as the hospital takes further
      initiatives to improve well-being.

PMID- 23968265
TI  - 'A one-to-one thing is better than a thousand books': views and understanding of
      older people with diabetes.
AB  - BACKGROUND: Specific aspects of care have been identified as important in order
      to provide high-quality care for patients with diabetes, including the need for
      patients to understand their condition. Little research has specifically explored
      the views and understanding of older people with diabetes in primary care. AIMS:
      To explore views on quality of diabetes care and to gauge patients' understanding
      of their condition in order to identify areas for improvement in care. METHODS:
      During August and September 2012, 13 semi-structured interviews were held with
      people with diabetes aged over 75 years, recruited from an inner-city general
      practice. The interviews focused on three areas: (1) their understanding of
      diabetes, (2) their views on the information they had received, and (3) their
      views on the quality of their care. The qualitative data were analysed using N
      Vivo and techniques derived from framework analysis. RESULTS: A basic
      understanding of diabetes was shared among the responders, but certain gaps were
      identified, notably misunderstandings regarding hypoglycaemia and diabetic coma.
      Information was valued most if given in person; written information may not be
      impactful. Educational input attenuated over time and patients did not actively
      seek updating. Personal care was appreciated, but many patients expressed a
      desire to be kept better informed about their treatment. CONCLUSIONS: Older
      people with diabetes wish to be involved in their care. Healthcare providers
      should regularly assess patients' knowledge in order to resolve potentially
      harmful misunderstandings. Explanations should be detailed and repeated, and
      sources of information need to be user-friendly as appropriate to this age group.
      Nurse-led, more continuous care was highly acceptable.

PMID- 23968266
TI  - Utilising the epidemiologic triad in analysing quality improvement data:
      antibiotic use for respiratory infections as a case example.
AB  - BACKGROUND: Quality improvement investigators working in field settings, who
      typically are not trained in epidemiological methods, may not consider all three
      elements of the epidemiologic triad (person, place and time) when planning their
      projects. AIM: To demonstrate how the epidemiological triad can guide analysis
      for quality assessment. Predictors of antibiotic use in primary care were
      analysed to illustrate the approach. METHODS: This study was a secondary analysis
      of data previously collected from medical records and a provider survey. A
      convenience sample of 467 family medicine patients treated in two clinic sites
      for acute respiratory tract infections was analysed by locating quality variation
      in person, place and time. Independent variables included patient age, date of
      clinic visit, and clinic site. The outcome measure was antibiotic prescription
      (yes or no). RESULTS: Antibiotics were prescribed for 69.2% of patients in the
      sample. Age group was not related to antibiotic prescribing. Prescription was
      related to time (P = 0.0344) and clinic site (P = 0.0001) in univariate tests.
      However, only site was independently related to antibiotic prescription (odds
      ratio = 0.47, confidence interval = 0.30 to 0.73, P = 0.0008). CONCLUSION: The
      epidemiological triad assisted in guiding further post hoc analysis of predictors
      of antibiotic prescriptions. Further investigations of this quality indicator can
      be directed at exploring site differences and testing interventions. Studies of
      other quality indicators in primary care can employ the triad to guide the
      analysis.

PMID- 23968267
TI  - Outcomes for collaborative care versus routine care in the management of
      postpartum depression.
AB  - BACKGROUND: Even with routine screening, women diagnosed with postpartum
      depression (PPD) often experience delays in treatment with consequences affecting
      mother, infant, families and communities. A collaborative care management (CCM)
      approach may provide more timely, effective and higher quality of care for women
      suffering from postpartum depression. AIMS: This study compared the outcomes of
      women diagnosed with depression within a year of giving birth, comparing
      management using a collaborative care model with routine primary care. METHODS:
      In a retrospective quantitative cohort pilot study (n = 78), the outcomes of days
      to first follow-up, one-year healthcare utilisation, remission rates and other
      quality metrics were investigated. RESULTS: Those who were managed with CCM had
      fewer days to first follow-up (6.1 versus 31.4; P < 0.01), were more likely to
      meet the quality metrics of three or more related contacts in the three months
      after diagnosis (P < 0.01), and had documented Patient Health Questionnaire (PHQ
      9) or Edinburgh Postnatal Depression Scale (EPDS) measurements at 3 (P < 0.01), 6
      (P < 0.01) and 12 (P < 0.01) months. With an intention to treat model, 6-month
      remission rates were improved with CCM (46.7 vs. 6.3%, P <0.01). Those managed
      collaboratively versus routinely used healthcare in the year following diagnosis
      at similar rates. CONCLUSIONS: A CCM model offers timelier and higher quality
      care to women suffering from PPD, without contributing to higher healthcare
      utilisation.

PMID- 23968268
TI  - Understanding processes and how to improve them.
AB  - This is the second in a series of articles about the science of quality
      improvement. Many quality improvement initiatives are aimed at improving the
      process of care and ensuring that high-quality care is delivered reliably. In
      this article, we explain why it is important to understand healthcare processes
      in order to improve them and how this can be achieved. We explain the use of
      logic models to determine what information to collect (from surveys, interviews,
      direct observations and other sources) and how to analyse this information (using
      techniques such as process maps, critical-to-quality trees, driver diagrams and
      cause-and-effect diagrams) to design more reliable and higher quality healthcare
      processes. 

PMID- 23968269
TI  - Should healthy populations be screened for breast cancer? A perspective from
      someone with previously diagnosed breast cancer.

PMID- 23968270
TI  - Should healthy populations be screened for breast cancer? A consultant surgeon's
      perspective.

PMID- 23968271
TI  - Impact of continuity on quality of primary care: from the perspective of
      citizens' preferences and multimorbidity - position paper of the European Forum
      for Primary Care.
AB  - BACKGROUND: Continuity of care is one of the cornerstones of primary care.
      Initially, the concept of continuity largely corresponded to one care provider
      and continuity between doctor and patient, but today, healthcare processes and
      organisations have grown and become more complex. A survey of patients with
      complex care needs found that in all of 11 countries studied care was often
      poorly coordinated. Multidimensional models of continuity have to be developed.
      AIM: To study existing evidence concerning significance of continuity in primary
      care with special consideration given to the preferences of citizens and to
      patients with complex care needs. METHODS: Contemporary literature was studied
      from the aspects of primary care, patients' point of view, multimorbidity and
      organisational models. Examples from country systems were collected. The topic
      and drafts were presented and discussed at two EFPC conference workshops.
      RESULTS: Evidence shows that both patients and caregivers identify and value
      continuity in the form of regular sources of care, and that provider continuity
      is related to lower total healthcare costs on a macro level. Continuity is a
      considerable component of quality in primary care. Methods to measure and compare
      between primary care centres, organisations and countries to stimulate
      improvements in continuity is lacking. The complexity of operationalising
      continuity in the context of multidisciplinary team-based primary care today and
      in the future remains a challenge. CONCLUSIONS: Continuity is, and will be, an
      important component of quality in primary care, especially from the perspective
      of citizens and growing multimorbidity. Methods to develop continuity should be
      promoted.

PMID- 23968273
TI  - Intraventricular haemorrhage in preterm infants--can we improve outcome by
      addressing coagulation?
AB  - During the last few decades, the survival of preterm infants has increased
      dramatically. Nevertheless, with the increasing number of very young and
      extremely low birth weight infants, morbidity is still a major problem.
      Intraventricular Haemorrhage (IVH) is a major complication of preterm birth, and
      large haemorrhages or haemorrhages associated with parenchymal brain lesions may
      yield a high rate of future disability. IVH is a complex, multi-factorial
      disorder. Prematurity and low birth weight remain as its most important risk
      factors, affecting vulnerability of the germinal matrix as well as the
      coagulation system. Approximately 80% of IVHs occur by 72 h after birth, but a
      considerable proportion of IVH is already visible on the first cranial ultrasound
      scan within a few hours of birth. The hypothesis that a severe coagulation
      deficiency in the premature newborn could be a major contributing factor to IVH
      has been suggested, and small open label interventional studies targeting the
      premature coagulation system have been conducted with ethamsylate, vitamin K,
      fresh frozen plasma, recombinant activated factor VII and prothrombin complex
      concentrate. The outcome of these studies will be reviewed. 

PMID- 23968274
TI  - Consequences and adaptation in daily life - patients' experiences three decades
      after a nerve injury sustained in adolescence.
AB  - BACKGROUND: To explore the patients' experiences during the three decades
      following repair of a nerve injury in the forearm and its consequences for daily
      life. Strategies that were used to facilitate adaptation were also investigated.
      METHODS: Fifteen participants with a complete median and/or ulnar nerve injury
      repaired in the ages from 13-20 years were interviewed using a semi-structured
      interview guide. The median follow-up time was 31 years (range 23-40). The
      participants were asked to describe the past and present symptoms of the injured
      hand, the consequences of the injury for daily life, personal qualities and
      support from others. In addition, they were asked to describe strategies used to
      facilitate adaptation. The interviews were subjected to content analysis.
      RESULTS: The nerve injury lead to sensory and motor deficits in the injured hand,
      as well as sensitivity to cold and secondary back problems. Emotional reactions
      to trauma and symptoms related to post-traumatic stress disorder were described,
      as well as how they managed to cope with such reactions. There was a noticeable
      impact on education, leisure, professional or domestic life for some, while
      others could continue by changing e.g. their performance pattern. The
      participants' life roles and relations were also affected. Both emotion- and
      problem-based strategies were used to manage challenges in daily life.
      CONCLUSIONS: The present qualitative study can help us to provide the patient
      with honest and realistic information about what to expect after a nerve injury
      at forearm level, without eliminating hope. Emotional reactions to trauma should
      be identified and dealt with. In addition, health-care professionals can promote
      a variety of coping mechanisms to facilitate daily living for the injured
      patients.

PMID- 23968275
TI  - The cutaneous bacterium Janthinobacterium lividum inhibits the growth of
      Trichophyton rubrum in vitro.
AB  - BACKGROUND: Tinea pedis (athlete's foot) is a fungal infection that is both
      widespread and challenging to treat. Standard treatments consist of topical and
      systemic therapies of antifungal agents, such as miconazole, itraconazole, and
      terbinafine. The extended nature of topical therapy and the toxicity of long-term
      systemic therapy limit the utility of current treatments. An alternate approach
      relies on an understanding of bacterial-fungal interactions. Specifically, a
      probiotic antifungal bacterium such as Janthinobacterium lividum can counter
      infection; Janthinobacterium is a major constituent of the human skin microbiota.
      Janthinobacterium lividum has been shown to ameliorate the effects of the
      cutaneous fungal disease chytridiomycosis in a vertebrate species (Rana muscosa).
      METHODS: Dual-culture plate challenge assays were performed using J. lividum and
      Trichophyton rubrum, the leading cause of athlete's foot. RESULTS: In all cases,
      T. rubrum colonies grew significantly smaller when co-cultured with J. lividum.
      CONCLUSION: These in vitro results suggest that J. lividum merits further
      investigation as a human cutaneous probiotic.

PMID- 23968276
TI  - Solute diffusion in ionic liquids, NMR measurements and comparisons to
      conventional solvents.
AB  - Diffusion coefficients of a variety of dilute solutes in the series of 1-alkyl-1
      methylpyrrolidinium bis(trifluoromethanesulfonyl)imides ([Prn1][Tf2N], n = 3, 4,
      6, 8, and 10), trihexyltetracedecylphosphonium bis(trifluoromethanesulfonyl)imide
      [P14,666][Tf2N], and assorted imidazolium ionic liquids are measured using pulsed
      field gradient (1)H NMR. These data, combined with available literature data, are
      used to try to uncover the solute and solvent characteristics most important in
      determining tracer diffusion rates. Discussion is framed in terms of departures
      from simple hydrodynamic predictions for translational friction using the ratio
      zetaobs/zetaSE, where zetaobs is the observed friction, determined from the
      measured diffusion coefficient D via zetaobs = kBT/D, and zetaSE = 6pietaR is the
      Stokes friction on a sphere of radius R (determined from the solute van der Waals
      volume) in a solvent with viscosity eta. In the case of neutral solutes, the
      primary determinant of whether hydrodynamic predictions are accurate is the
      relative size of solute versus solvent molecules. A single correlation, albeit
      with considerable scatter, is found between zetaobs/zetaSE and the ratio of
      solute-to-solvent van der Waals volumes, zetaobs/zetaSE = {1 + a(VU/VV)(-p)},
      with constants a = 1.93 and p = 1.88. In the case of small solutes, the observed
      friction is over 100-fold smaller than predictions of hydrodynamic models. The
      dipole moment of the solute has little effect on the friction, whereas solute
      charge has a marked effect. For monovalent solutes of size comparable to or
      smaller than the solvent ions, the observed friction is comparable to or even
      greater than what is predicted by hydrodynamics. These general trends are shown
      to be quite similar to what is observed for tracer diffusion in conventional
      solvents. 

PMID- 23968277
TI  - Tumor necrosis factor-like weak inducer of apoptosis and its receptor fibroblast
      growth factor-inducible 14 are expressed in urticarial vasculitis.
AB  - Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), a member of
      the TNF family, has been implicated as a pro-inflammatory cytokine in many types
      of autoimmune and infectious diseases. However, information about TWEAK in
      dermatological diseases is limited. To date, no studies have investigated the
      roles of TWEAK in patients with urticarial vasculitis (UV). This study aimed to
      assess serum TWEAK levels, together with TWEAK and fibroblast growth factor
      inducible 14 (Fn14) expressions of skin lesions in patients with UV. Serum TWEAK
      levels in patients with UV, together with patients with cutaneous
      leukocytoclastic angiitis (CLA) and healthy controls were detected by enzyme
      linked immunosorbent assay; TWEAK and Fn14 expressions of skin lesions were
      analyzed by immunohistochemistry. Results showed that TWEAK and Fn14 were
      abundantly expressed in the dermal vessel wall of lesional skin in patients with
      UV but not healthy controls. Serum TWEAK levels in the acute stage in patients
      with UV were significantly higher than those in the convalescent stage and
      healthy controls. Serum TWEAK levels were elevated significantly in patients with
      CLA compared with those in healthy controls. Our previous study indicated that
      TWEAK may be an important mediator for the development of vascular inflammation
      in skin. In addition, we also found that TWEAK blockade substantially reduced
      vascular damage and perivascular leukocyte infiltrates in lipopolysaccharide
      induced cutaneous vasculitis. Our study shows that TWEAK may be associated with
      the pathogenesis of UV; it is therefore suggested that TWEAK may be a potential
      therapeutic target for UV and other types of cutaneous vasculitis. 

PMID- 23968278
TI  - Palladium-catalyzed coupling reactions for the functionalization of Si surfaces:
      superior stability of alkenyl monolayers.
AB  - Palladium-catalyzed Suzuki, Heck, and Sonogashira coupling reactions were studied
      as reaction protocols for organic modification of Si surfaces. These
      synthetically useful protocols allow for surface modification of alkene, alkyne,
      and halide terminated surfaces. Surface oxidation and metal contamination were
      assessed by X-ray photoelectron spectroscopy. The nature of the primary
      passivation layer was an important factor in the oxidation resistance of the Si
      surface during the secondary functionalization. Specifically, the use of alkynes
      as the primary functionalization layer gave superior stability compared to alkene
      analogues. The ability to utilize Pd-catalyzed coupling chemistries on Si
      surfaces opens great versatility for potential molecular and nanoscale
      electronics and sensing/biosensing applications. 

PMID- 23968280
TI  - Reduction of Yb(III) to Yb(II) by two-color two-photon excitation.
AB  - Ytterbium 3+ ions in alcohol were found to be reduced to the corresponding 2+
      ions upon laser irradiation with a stepwise two-color two-photon excitation. The
      infrared (975-nm) pulse with a duration of 4 ns pumps the ground state to the 4f
      excited state with the transition of (2)F(5/2) <- (2)F(7/2), and the second
      photon (355-nm) generates the charge transfer (CT) state of Cl 3p to Yb 4f; the
      reduction then occurs. Laser energy and excitation wavelength dependencies well
      explain the above mechanism. The product Yb(2+) was detected by its absorption
      spectrum peak at 367 nm. The absorption spectrum of the intermediate in the two
      photon chemistry was measured from the 4f excited state ((2)F(5/2)) to the CT
      state by nanosecond laser photolysis. The intermediate spectrum appears in the
      wavelengths shorter than 400 nm with the molar extinction coefficient on the
      order of (10(2) M(-1) cm(-1)) at 340 nm and can be explained in terms of the CT
      absorption shifted by IR photon energy. A UV nanosecond laser pulse (266 nm from
      a YAG laser with a duration of 6 ns) can generate the reactive CT state by one
      photon absorption and leads to Yb(2+) formation. The reaction yields for single
      photon UV excitation and the second photon in the two-photon excitation are on
      the order of 0.1, suggesting that the reactive states are a common CT state.

PMID- 23968279
TI  - Complete mitogenome of Asiatic lion resolves phylogenetic status within Panthera.
AB  - BACKGROUND: The origin, evolution and speciation of the lion, has been subject of
      interest, debate and study. The present surviving lions of the genus Panthera
      comprise of eight sub-species inclusive of Asiatic lion Panthera leo persica of
      India's Gir forest. Except for the Asiatic lion, the other seven subspecies are
      found in different parts of Africa. There have been different opinions regarding
      the phylogenetic status of Panthera leo, as well as classifying lions of
      different geographic regions into subspecies and races. In the present study,
      mitogenome sequence of P. leo persica deduced, using Ion Torrent PGM to assess
      phylogeny and evolution which may play an increasingly important role in
      conservation biology. RESULTS: The mtDNA sequence of P. leo persica is 17,057 bp
      in length with 40.8% GC content. Annotation of mitogenome revealed total 37
      genes, including 13 protein coding, 2 rRNA and 22 tRNA. Phylogenetic analysis
      based on whole mitogenome, suggests Panthera pardus as a neighbouring species to
      P. leo with species divergence at ~2.96 mya. CONCLUSION: This work presents first
      report on complete mitogenome of Panthera leo persica. It sheds light on the
      phylogenetic and evolutionary status within and across Felidae members. The
      result compared and evaluated with earlier reports of Felidae shows alteration of
      phylogenetic status and species evolution. This study may provide information on
      genetic diversity and population stability.

PMID- 23968281
TI  - Full "Laplacianised" posterior naive Bayesian algorithm.
AB  - BACKGROUND: In the last decade the standard Naive Bayes (SNB) algorithm has been
      widely employed in multi-class classification problems in cheminformatics. This
      popularity is mainly due to the fact that the algorithm is simple to implement
      and in many cases yields respectable classification results. Using clever
      heuristic arguments "anchored" by insightful cheminformatics knowledge, Xia et
      al. have simplified the SNB algorithm further and termed it the Laplacian
      Corrected Modified Naive Bayes (LCMNB) approach, which has been widely used in
      cheminformatics since its publication.In this note we mathematically illustrate
      the conditions under which Xia et al.'s simplification holds. It is our hope that
      this clarification could help Naive Bayes practitioners in deciding when it is
      appropriate to employ the LCMNB algorithm to classify large chemical datasets.
      RESULTS: A general formulation that subsumes the simplified Naive Bayes version
      is presented. Unlike the widely used NB method, the Standard Naive Bayes
      description presented in this work is discriminative (not generative) in nature,
      which may lead to possible further applications of the SNB method. CONCLUSIONS:
      Starting from a standard Naive Bayes (SNB) algorithm, we have derived
      mathematically the relationship between Xia et al.'s ingenious, but heuristic
      algorithm, and the SNB approach. We have also demonstrated the conditions under
      which Xia et al.'s crucial assumptions hold. We therefore hope that the new
      insight and recommendations provided can be found useful by the cheminformatics
      community.

PMID- 23968283
TI  - Anodal transcranial direct current stimulation over the supramarginal gyrus
      facilitates pitch memory.
AB  - Functional neuroimaging studies have shown activation of the supramarginal gyrus
      during pitch memory tasks. A previous transcranial direct current stimulation
      study using cathodal stimulation over the left supramarginal gyrus reported a
      detrimental effect on short-term pitch memory performance, indicating an
      important role of the supramarginal gyrus in pitch memory. The current study
      aimed to determine whether pitch memory could be improved following anodal
      stimulation of the left supramarginal gyrus. The performances of non-musicians on
      two pitch memory tasks (pitch recognition and recall) and a visual memory control
      task following anodal or sham transcranial direct current stimulation were
      compared. The results show that, post-stimulation, the anodal group but not the
      control group performed significantly better on both pitch memory tasks;
      performance did not differ on the face memory task. These findings provide strong
      support for the causal involvement of the left supramarginal gyrus in the pitch
      memory process, and highlight the potential efficacy of transcranial direct
      current stimulation as a tool to improve pitch memory. 

PMID- 23968284
TI  - A multi-modal training programme to improve physical activity, physical fitness
      and perceived physical ability in obese children.
AB  - Actual and perceived physical abilities are important correlates of physical
      activity (PA) and fitness, but little research has explored these relationships
      over time in obese children. This study was designed: (a) to assess the
      feasibility of a multi-modal training programme promoting changes in PA,
      fundamental motor skills and real and perceived physical abilities of obese
      children; and (b) to explore cross-sectional and longitudinal relationships
      between real and perceived physical competence in boys and girls. Forty-one
      participants (9.2 +/- 1.2 years) were assessed before and after an 8-month
      intervention with respect to body composition, physical fitness, self-reported PA
      and perceived physical ability. After treatment, obese children reported
      improvements in the body mass index, PA levels, gross motor performance and
      actual and perceived physical abilities. Real and perceived physical competence
      was correlated in boys, but not in girls. Results indicate that a multi-modal
      programme focused on actual and perceived physical competence as associated with
      the gradual increase in the volume of activity might be an effective strategy to
      improve adherence of the participants and to increase the lifelong exercise
      skills of obese children.

PMID- 23968282
TI  - The hyperferritinemic syndrome: macrophage activation syndrome, Still's disease,
      septic shock and catastrophic antiphospholipid syndrome.
AB  - BACKGROUND: Over the last few years, accumulating data have implicated a role for
      ferritin as a signaling molecule and direct mediator of the immune system.
      Hyperferritinemia is associated with a multitude of clinical conditions and with
      worse prognosis in critically ill patients. DISCUSSION: There are four uncommon
      medical conditions characterized by high levels of ferritin, namely the
      macrophage activation syndrome (MAS), adult onset Still's disease (AOSD),
      catastrophic antiphospholipid syndrome (cAPS) and septic shock, that share a
      similar clinical and laboratory features, and also respond to similar treatments,
      suggesting a common pathogenic mechanism. Ferritin is known to be a pro
      inflammatory mediator inducing expression of pro-inflammatory molecules, yet it
      has opposing actions as a pro-inflammatory and as an immunosuppressant. We
      propose that the exceptionally high ferritin levels observed in these uncommon
      clinical conditions are not just the product of the inflammation but rather may
      contribute to the development of a cytokine storm. SUMMARY: Here we review and
      compare four clinical conditions and the role of ferritin as an immunomodulator.
      We would like to propose including these four conditions under a common syndrome
      entity termed "Hyperferritinemic Syndrome".

PMID- 23968285
TI  - Silver and gold nanostructures: antifungal property of different shapes of these
      nanostructures on Candida species.
AB  - The shape of nanoparticles is an important determinant of their physical and
      chemical properties, possibly including the little-explored area of their use as
      antifungal agents. Therefore, we evaluated the in vitro antifungal activities of
      three different shapes of silver and gold nanostructures, including nanocubes,
      nanospheres, and nanowires, on Candida albicans, C. glabrata and C. tropicalis,
      using the microdilution and disk diffusion methods as per the guidelines of the
      Clinical and Laboratory Standards Institute. We found that silver and gold
      nanocubes had higher antifungal properties against the test species than
      nanospheres and nanowires. While some isolates were resistant to silver and gold
      nanospheres and nanowires, none of the isolates were resistant to silver and gold
      nanocubes. The occurrence of resistance is a new finding which should be further
      explored. 

PMID- 23968286
TI  - Has the impact of the working time regulations changed neurosurgical trainees'
      attitudes towards the European working time directive 5 years on?
AB  - We report the results from a survey of the British Neurosurgical Trainees'
      Association which aimed to assess current rota patterns and their compliance with
      the government's working time regulations. The survey questioned whether trainees
      felt that shift working, imposed as a result of the European working time
      directive, is continuing to impact on patient care and training opportunities in
      neurosurgery. The responses to this survey indicate that neurosurgical trainees
      remain concerned with the impact that the current working time regulations have
      on all facets of their work: training, work- life balance, and the provision of
      patient care. The survey comments show that the majority would support a change
      in legislation to allow greater flexibility in the working time regulations.

PMID- 23968287
TI  - Water oxidation mechanism for synthetic Co-oxides with small nuclearity.
AB  - Hybrid DFT model calculations have been performed for some cobalt complexes
      capable of oxidizing water. Since a very plausible mechanism for the oxygen
      evolving complex involving the cuboidal Mn4Ca structure in photosystem II (PSII)
      has recently been established, the most important part of the present study
      concerns a detailed comparison between cobalt and manganese as water oxidation
      catalysts. One similarity found is that a M(IV)-O(*) state is the key precursor
      for O-O bond formation in both cases. This means that simply getting a M(IV)
      state is not enough; a formal M(V)?O state is required, with two oxidations on
      one center from M(III). For cobalt, not even that is enough. A singlet coupled
      state is required at this oxidation level, which is not the ground state. It is
      shown that there are also more fundamental differences between catalysts based on
      these metals. The favorable low-barrier direct coupling mechanism found for PSII
      is not possible for the corresponding cobalt complexes. The origin of this
      difference is explained. For the only oxygen-evolving cubic Co4O4 complex with a
      defined structure, described by Dismukes et al., the calculated results are in
      good agreement with experiments. For the Co4 models of the amorphous cobalt-oxo
      catalyst found by Nocera et al., higher barriers are found than the one obtained
      experimentally. The reasons for this are discussed. 

PMID- 23968289
TI  - Intraoperative complications during sinus floor elevation using two different
      ultrasonic approaches: a two-center, randomized, controlled clinical trial.
AB  - PURPOSE: The aim of this study was to assess the prevalence of intraoperative
      complications during maxillary sinus elevation with lateral approach using a
      piezoelectric device with two different surgical techniques. MATERIALS AND
      METHODS: Antrostomies were randomly performed by outlining a window (group A, 36
      patients) or by eroding the cortical wall with a grinding insert until the
      membrane was visible under a thin layer of bone, before outlining the window
      (group B, 36 patients). Occurrence of membrane perforation, laceration of
      vascular branches, and surgical time was recorded. RESULTS: Seventy-two patients
      underwent sinus floor elevation: four perforations (11.1%) were observed in group
      A (two occurred during elevation with hand instruments) and zero perforations in
      group B (p < .05). No evidence of vascular lacerations was registered in both
      groups. A clinically insignificant but statistically shorter surgical time was
      recorded in group A (9.2 +/- 3.7 minutes) than in group B (13.3 +/- 2.4 minutes;
      p < .05). CONCLUSIONS: Within the limits of the present study, it may be
      concluded that ultrasonic erosion of the lateral wall of the sinus is a more
      predictable technique than piezoelectric outlining of a bone window in preventing
      from accidental perforations of Schneiderian membrane during sinus augmentation
      procedures.

PMID- 23968290
TI  - Fine-tuning the electrostatic properties of an alkali-linked organic adlayer on a
      metal substrate.
AB  - The performance of modern organic electronic devices is often determined by the
      electronic level alignment at a metal-organic interface. This property can be
      controlled by introducing an interfacial electrostatic dipole via the insertion
      of a stable interlayer between the metallic and the organic phases. Here, we use
      density functional theory to investigate the electrostatic properties of an
      assembled structure formed by alkali metals coadsorbed with 7,7,8,8
      tetracyanoquinodimethane (TCNQ) molecules on a Ag(100) substrate. We find that
      the interfacial dipole buildup is regulated by the interplay of adsorption
      energetics, steric constraints and charge transfer effects, so that choosing
      chemical substitutions within TCNQ and different alkali metals provides a rich
      playground to control the systems' electrostatics and in particular fine-tune its
      work-function shift. 

PMID- 23968291
TI  - River blindness eliminated in Colombia.

PMID- 23968292
TI  - Different gestational ages and changing vulnerability of the premature brain.
AB  - In recent decades, there has been a general increase in survival rates of preterm
      and low birth weight infants, but this overall decrease in perinatal mortality
      has not been accompanied by a decrease in long-term physical and mental
      disability. In order to reduce the long-term sequelae of prematurity and to
      establish preventive measures, it is important to identify risk factors since the
      main determinant of specific vulnerability to different types of lesions is
      gestational age. The regional tissue vulnerability at a given gestational age is
      probably determined by the local metabolic requirements together with specific
      cell characteristics and their level of maturation. In this article, we discuss
      the most common neonatal cerebral lesions (cerebellar haemorrhage, germinal
      matrix intraventricular haemorrhage, periventricular leukomalacia, arterial
      ischaemic stroke, cerebral vein sinus thrombosis and hypoxic-ischaemic
      encephalopathy) related to the gestational age-dependent vulnerability of the
      premature brain. 

PMID- 23968293
TI  - Enteric pathogens, immune status and therapeutic response in diarrhea in HIV/AIDS
      adult subjects from north India.
AB  - Intestinal infection causing diarrheal disease is a dominant contributor to high
      morbidity and mortality in developing countries. This intervention study aimed to
      assess the response of specific anti-microbial and anti-retroviral therapy (ART)
      on enteropathogens identified in HIV/AIDS adult subjects from northern India.
      Seventy five ART naive (group 1) and seventy five ART adherent (group 2) HIV/AIDS
      adult subjects with diarrhea were enrolled. Stool samples from all subjects were
      examined for enteropathogens by wet mount, staining methods, culture and ELISA.
      Subjects with enteropathogens were started on specific therapy as per National
      AIDS Control Organisation, Government of India's guidelines. Follow-up stool
      samples were examined after 2-4 weeks of completion of therapy for
      persistence/clearing of enteropathogens. CD4+ T lymphocyte count was done for all
      subjects. At enrollment, group 1 had 26.13% bacterial, 57.66% parasitic & 16.22%
      fungal pathogens while group 2 had 11.9%, 69.05% & 19.05% pathogens,
      respectively. Parasitic diarrhea was more common than bacterial diarrhea. The
      coccidian parasites (Cryptosporidium spp. & Isospora belli) were the common
      parasites identified. Clearance of enteric pathogens was significant after
      specific anti-microbial therapy (p = 0.0001). Persistence of enteropathogens was
      seen primarily for coccidian parasites. Clearance of enteropathogens after
      specific therapy and the diagnostic yield of stool specimens were influenced by
      the CD4+ counts. Immune competence coupled with specific anti-microbial therapy
      displays the best response against enteric pathogens. 

PMID- 23968295
TI  - Ultrasonic and densimetric characterization of the association of cyclic AMP with
      the cAMP-binding domain of the exchange protein EPAC1.
AB  - We employed a combination of densimetric and ultrasonic velocimetric techniques
      to characterize the volumetric properties of the association of the cAMP-binding
      domain (CBD) of EPAC1 with cAMP at 25  degrees C in a pH 7.6 buffer. The binding
      of cAMP to the CBD of EPAC1 is accompanied by changes in volume, DeltaV, and
      adiabatic compressibility, DeltaKS, of -59 +/- 4 cm(3) mol(-1) and (34 +/- 9) *
      10(-4) cm(3) mol(-1) bar(-1), respectively. We use these volumetric results in
      conjunction with the structural data to estimate a change in hydration, Deltanh,
      accompanying the binding. We calculate that approximately 103 water molecules are
      released to the bulk from the associating surfaces of the protein and the ligand.
      This number is ~30% larger than the number of water molecules in direct contact
      with the associating surfaces while also being within the error of our Deltanh
      determination. Therefore, we conclude that cAMP binding to EPAC1 may involve, in
      addition to the waters from within the first coordination sphere, also some
      waters from the second coordination sphere of the protein and cAMP. Our analysis
      of the compressibility data reveals that the protein becomes more rigid and less
      dynamic upon the cAMP binding as reflected in a 4 +/- 0.5% decrease in its
      intrinsic coefficient of adiabatic compressibility. Finally, we estimate the
      hydration, DeltaShyd, and configurational, DeltaSconf, contributions to the
      binding entropy, DeltaSb. We find that the binding entropy is determined by the
      fine balance between the DeltaShyd and DeltaSconf terms. In general, we discuss
      insights that are derived from a combination of volumetric and structural
      properties, in particular, emphasizing how measured changes in volume and
      compressibility can be interpreted in terms of hydration and dynamic properties
      of EPAC1 in its apo- and holo-forms. 

PMID- 23968294
TI  - Optimisation of the foot-and-mouth disease virus 2A co-expression system for
      biomedical applications.
AB  - BACKGROUND: Many biomedical applications require the expression or production of
      therapeutic hetero-multimeric proteins/protein complexes: in most cases only
      accomplished by co-ordinated co-expression within the same cell. Foot-and-mouth
      disease virus 2A (F2A) and '2A-like' sequences are now widely used for this
      purpose. Since 2A mediates a co-translational 'cleavage' at its own C-terminus,
      sequences encoding multiple proteins (linked via 2As) can be concatenated into a
      single ORF: a single transgene. It has been shown that in some cases, however,
      the cleavage efficiency of shorter versions of F2A may be inhibited by the C
      terminus of certain gene sequences immediately upstream of F2A. This paper
      describes further work to optimise F2A for co-expression strategies. RESULTS: We
      have inserted F2A of various lengths in between GFP and CherryFP 'reporter'
      proteins (in reciprocal or tandem arrangements). The co-expression of these
      proteins and cleavage efficiencies of F2As of various lengths were studied by in
      vitro coupled transcription and translation in rabbit reticulocyte lysates,
      western blotting of HeLa cell lysates and fluorescence microscopy. CONCLUSIONS:
      Optimal and suboptimal lengths of F2A sequences were identified as a result of
      detailed 'fine-tuning' of the F2A sequence. Based on our data and the model
      according to which 2A activity is a product of its interaction with the exit
      tunnel of the ribosome, we suggest the length of the F2A sequence which is not
      'sensitive' to the C-terminus of the upstream protein that can be successfully
      used for co-expression of two proteins for biomedical applications.

PMID- 23968296
TI  - Ten-year publication trends in dermatology in mainland China.
AB  - BACKGROUND: China has been experiencing huge changes in all aspects, including
      dermatologic research, since its reform in 1978. However, it is not known how the
      economic and intellectual development has influenced the publication trends in
      the field of dermatology, which could mirror the scientific development in other
      medical disciplines. In the present study, we analyzed publication trends from
      dermatology departments in mainland China from 2002 to 2011. METHODS: All
      publication data were obtained from www.pubmed.com. Only papers published from
      dermatology departments in mainland China were used for analysis. RESULTS: The
      number of publications increased 10-fold over this 10-year period. A total of
      1231 articles were published in English in 251 journals between 2002 and 2011. A
      total of 129 journals published only one paper from dermatology departments in
      mainland China. Over 60% of articles were original research, and 21.7% were case
      reports. Among these 251 journals, foremost was the Journal of Clinical
      Experimental Dermatology, which published 5.9% of all papers from mainland China;
      2.7% of papers were published in the Journal of Investigative Dermatology. The
      number of publications positively correlated with the changes in gross domestic
      product per capita during the study period. CONCLUSIONS: These results suggest
      that the number of publications in the dermatology field has increased markedly
      in mainland China over the last 10 years. This dramatic increase in publications
      could be attributed, at least partially, to the significant improvement in
      economic conditions in mainland China.

PMID- 23968298
TI  - Changing CPAP tubing on a neonatal unit.

PMID- 23968297
TI  - Catalytic hydrogenation activity and electronic structure determination of
      bis(arylimidazol-2-ylidene)pyridine cobalt alkyl and hydride complexes.
AB  - The bis(arylimidazol-2-ylidene)pyridine cobalt methyl complex, ((iPr)CNC)CoCH3,
      was evaluated for the catalytic hydrogenation of alkenes. At 22  degrees C and 4
      atm of H2 pressure, ((iPr)CNC)CoCH3 is an effective precatalyst for the
      hydrogenation of sterically hindered, unactivated alkenes such as trans
      methylstilbene, 1-methyl-1-cyclohexene, and 2,3-dimethyl-2-butene, representing
      one of the most active cobalt hydrogenation catalysts reported to date.
      Preparation of the cobalt hydride complex, ((iPr)CNC)CoH, was accomplished by
      hydrogenation of ((iPr)CNC)CoCH3. Over the course of 3 h at 22  degrees C,
      migration of the metal hydride to the 4-position of the pyridine ring yielded (4
      H2-(iPr)CNC)CoN2. Similar alkyl migration was observed upon treatment of
      ((iPr)CNC)CoH with 1,1-diphenylethylene. This reactivity raised the question as
      to whether this class of chelate is redox-active, engaging in radical chemistry
      with the cobalt center. A combination of structural, spectroscopic, and
      computational studies was conducted and provided definitive evidence for
      bis(arylimidazol-2-ylidene)pyridine radicals in reduced cobalt chemistry. Spin
      density calculations established that the radicals were localized on the pyridine
      ring, accounting for the observed reactivity, and suggest that a wide family of
      pyridine-based pincers may also be redox-active. 

PMID- 23968299
TI  - Huntington's disease research and practice: reflections on the journey made and
      lessons learned.

PMID- 23968300
TI  - Musical hallucination in acquired and pre-lingual deafness.

PMID- 23968302
TI  - Poly(N-isopropylacrylamide)-stabilized gold nanoparticles in combination with
      tricationic branched phenylene-ethynylene fluorophore for protein identification.
AB  - Gold nanoparticles stabilized by thermoresponsive polymer, poly(N
      isopropylacrylamide) (PNIPAM-AuNPs) were prepared by surface grafting of thiol
      terminated PNIPAM onto citrate-stabilized AuNPs. The color change of the PNIPAM
      AuNPs solution from red to blue-purple without precipitation when the solution
      was heated to 40  degrees C, above the lower critical solution temperature (LCST)
      of PNIPAM, indicated the thermoresponsive property of the synthesized AuNPs.
      PNIPAM-AuNPs were used to detect proteins by chemical nose approach based on
      fluorescence quenching of fluorophore by AuNPs. An array-based sensing platform
      for detection of six proteins, namely bovine serum albumin, lysozyme, fibrinogen,
      concanavalin A, hemoglobin, holo-transferrin human can be successfully developed
      from the PNIPAM-AuNPs having different molecular weights (4 and 8 kDa) and
      conformation (varied heat treatment from 25 to 40  degrees C) in combination with
      a tricationic branched phenylene-ethynylene fluorophore. From principal component
      analysis (PCA) followed by linear discriminant analysis (LDA), 100% accuracy of
      protein classification using a leave-one-out (LOO) approach can be achieved by
      using only two types of PNIPAM-AuNPs. 

PMID- 23968301
TI  - Continuous theta-burst stimulation modulates tactile synchronization.
AB  - BACKGROUND: Temporal order judgement (TOJ) is the ability to detect the order of
      occurrence of two sequentially delivered stimuli. Previous research has shown
      that TOJ in the presence of synchronized periodic conditioning stimuli impairs
      TOJ performance, and this phenomenon is suggested to be mediated by GABAergic
      interneurons that cause perceptual binding across the two skin sites. Application
      of continuous theta-burst repetitive TMS (cTBS) over primary somatosensory cortex
      (SI) alters temporal and spatial tactile perception. The purpose of this study
      was to examine TOJ perception in the presence and absence of synchronized
      periodic conditioning stimuli before and after cTBS applied over left-hemisphere
      SI. A TOJ task was administered on the right index and middle finger (D2 and D3)
      in two separate sessions in the presence and absence of conditioning stimuli (a
      background low amplitude sinusoidal vibration). RESULTS: CTBS reduced the impact
      of the conditioning stimuli on TOJ performance for up to 18 minutes following
      stimulation while sham cTBS did not affect TOJ performance. In contrast, the TOJ
      task performed in the absence of synchronized conditioning stimulation was
      unaltered following cTBS. CONCLUSION: We conclude that cTBS suppresses inhibitory
      networks in SI that mediate perceptual binding during TOJ synchronization. CTBS
      offers one method to suppress cortical excitability in the cortex and potentially
      benefit clinical populations with altered inhibitory cortical circuits.
      Additionally, TOJ measures with conditioning stimuli may provide an avenue to
      assess sensory processing in neurologically impaired patient populations.

PMID- 23968303
TI  - Antioxidant treatment and outcome of Cortinarius orellanus poisoning: a case
      series.
AB  - OBJECTIVES: To study the frequency, severity, and long-term outcome of renal
      injury in Cortinarius orellanus poisoning, to evaluate the association between
      the ingested amount of C. orellanus and outcome, and to evaluate the effect of N
      acetylcysteine and corticosteroid treatment on outcome. METHODS: Case series of
      eight patients. Diagnosis and severity of acute kidney injury (AKI) and chronic
      kidney disease (CKD) were classified according to current AKI and CKD
      definitions. N-acetylcysteine and corticosteroids were administered to six
      patients, former according to the standard for paracetamol poisoning. MAIN
      FINDINGS: All patients developed AKI, six in the most severe stage and four
      required renal replacement therapy (RRT). After 12 months, seven patients
      presented with CKD, of whom three required chronic RRT and further two were in
      advanced CKD. AKI and CKD severity highly correlated with the consumed amounts of
      Cortinarius orellanus (r = 0.98, p < 0.001 and r = 0.78, p = 0.02, respectively)
      but not with N-acetylcysteine and corticosteroid treatment. CONCLUSIONS: AKI and
      CKD by current definitions and classifications are frequent and severe after
      Cortinarius orellanus poisoning. The ingested amount of Cortinarius orellanus
      correlates with the severity of both AKI and CKD. N-acetylcysteine and
      corticosteroid treatment do not seem to have a beneficial effect on either AKI or
      CKD.

PMID- 23968304
TI  - Multimodal imaging of sarcoid choroidal granulomas.
AB  - BACKGROUND: Enhanced-depth imaging optical coherence tomography (EDI-OCT)
      provides high-resolution imaging of the choroid. Herein, we report multimodal
      imaging, including EDI-OCT, of a case of sarcoid choroidal granulomas. FINDINGS:
      A 63-year-old female with biopsy-supported sarcoidosis presented with unilateral
      multifocal choroidal granulomas. Enhanced-depth imaging optical coherence
      tomography (EDI-OCT) demonstrated a homogenous hyporeflective choroidal lesion
      with choriocapillaris thinning and sparing of the surrounding choroid. The
      patient was started on oral steroids with a weekly taper schedule. Within 5
      weeks, the choroidal lesions had clinically resolved with return of normal
      appearing choroidal architecture on EDI-OCT. Indocyanine green angiography,
      however, demonstrated hypofluoresence at the sites of choroidal granulomas 11
      months after the clinical resolution, suggesting a longstanding choroidal
      perfusion deficit undetected by OCT. CONCLUSIONS: Choroidal imaging via EDI-OCT
      provides detailed morphologic information of sarcoid granulomas and can
      accurately demonstrate structural resolution of the lesions.

PMID- 23968305
TI  - Hispanic parents' reading language preference and pediatric oral health-related
      quality of life.
AB  - OBJECTIVES: This study compared scores and psychometric properties from self
      identified Hispanic parents who completed Pediatric Oral Health-related Quality
      of life (POQL) parent report-on-child questionnaires in Spanish or English. The
      study hypothesized that there were no differences in psychometric properties or
      POQL scores by parent reading language preference, controlling for dental needs,
      child's place of birth, age, insurance and use of care. METHODS: POQL scores were
      computed, and the internal consistency, feasibility, factor structure and
      construct validity of the Spanish language version assessed. RESULTS: Hispanic
      parents (N = 387) of 8-14 year old children (mean age 10.2) completed the survey;
      237 in Spanish and 150 in English. Internal consistency scores were higher
      (Cronbach alpha range = .86-.93) among Hispanic parents who completed the
      questionnaire in Spanish than in English (.66-.86). POQL scores from parents who
      completed questionnaires in Spanish were higher (worse) overall (6.03 vs. 3.82, P
      = 0.022), as were physical (11.61 vs. 6.54, P = 0.001) and role functioning
      domains (1.87 vs. 0.82, P = 0.029). Items for crying, pain, and eating were
      higher (P < 0.05) for the Spanish than the English completers. However, POQL
      scores were associated only with need for care (P = 0.05), parent reports of
      dental visit in the last year (P = 0.05) and worse oral health than a year ago (P
      = 0.002), controlling for reading language (not significant) and visit in last
      year in the final multivariate linear regression.

PMID- 23968306
TI  - Availability and components of maternity services according to providers and
      users perspectives in North Gondar, Northwest Ethiopia.
AB  - BACKGROUND: The goal of reducing maternal mortality can be achieved when women
      receive important service components at the time of their maternity care. This
      study attempted to assess the availability and the components of maternity
      services according to the perspectives of service users and providers. METHOD: A
      linked facility and population-based survey was conducted over three months
      (January to March 2012) in North Gondar Zone. Twelve kebeles (clusters) were
      selected randomly from six districts to identify maternity clients cared for by
      skilled providers. Then 12 health centers and 3 hospitals utilized by the
      corresponding cluster population were selected for facility survey. Interview
      with facility managers/heads, providers and clients and observations were used
      for data collection. Data were entered using Epi Info and were exported to SPSS
      software for analysis. RESULTS: Antenatal and delivery care were available in
      most of the visited facilities. However, the majority of them were not fully
      functioning for EmOC according to their level. Signal functions including
      administration of anticonvulsants and assisted vaginal delivery were missing in
      seven and five of the 12 health centers, respectively. Only one hospital met the
      criteria for comprehensive emergency obstetric care (performed cesarean section).
      Only 24% of the providers used partograph consistently. About 538 (32.3%) and 231
      (13.8%) of the women received antenatal and delivery care from skilled providers,
      respectively. Most of the services were at health centers by nurses/midwives. At
      the time of the antenatal care, women received the important components of the
      services (percentage of users in bracket) like blood pressure checkup (79%),
      urine testing (35%), tetanus immunization (45%), iron supplementation (64%),
      birth preparedness counseling (51%) and HIV testing (71%). During delivery, 80%
      had their blood pressure measured, 78% were informed on labor progress, 89% had
      auscultation of fetal heartbeat, 80% took drugs to prevent bleeding and 78% had
      counseling on early & exclusive breast-feeding. CONCLUSION: Antenatal and
      delivery care were available in most of the visited facilities. However,
      important components of both the routine and emergency maternity care services
      were incomplete. Improving the functional capacity of health facilities for the
      delivery of routine maternity and EmOC services are needed.

PMID- 23968307
TI  - Electrospray ionization from nanopipette emitters with tip diameters of less than
      100 nm.
AB  - Work presented here demonstrates application of nanopipettes pulled to orifice
      diameters of less than 100 nm as electrospray ionization emitters for mass
      spectrometry. Mass spectrometric analysis of a series of peptides and proteins
      electrosprayed from pulled-quartz capillary nanopipette emitters with internal
      diameters ranging from 37 to 70 nm is detailed. Overall, the use of nanopipette
      emitters causes a shift toward the production of ions of higher charge states and
      leads to a reduction in width of charge-state distribution as compared to typical
      nanospray conditions. Further, nanopipettes show improved S/N and the same signal
      precision as typical nanospray, despite the much smaller dimensions. As
      characterized by SEM images acquired before and after spray, nanopipettes are
      shown to be robust under conditions employed. Analytical calculations and
      numerical simulations are used to calculate the electric field at the emitter
      tip, which can be significant for the small diameter tips used. 

PMID- 23968308
TI  - Radiographic monitoring of changes in bone height after implant placement in
      combination with an internal sinus lift without graft material.
AB  - PURPOSE: The objective was to investigate changes in bone height after implant
      placement in combination with simultaneous internal sinus lift (ISL) without
      graft material. MATERIALS AND METHODS: For a retrospective clinical study, 101
      implants placed in combination with ISL without graft were selected. The study
      included 66 patients (mean age 59.6 years) with radiographs from baseline (T0)
      and two follow-ups after mean times of 7 months (T1) and 17 months (T2). Apical
      changes in bone height were measured at the mesial and distal aspects of the
      implant. Correlation analysis was performed to identify factors affecting changes
      in bone height. RESULTS: Mean apical bone gains of 1.0 mm (mesial) and 1.7 mm
      (distal) were observed at T1. At T2, mean apical bone gains were 1.5 mm and 2.1
      mm (distal). The change in apical bone height was significant between T0 and T1,
      between T0 and T2, and between T1 and T2. Rank correlation analysis revealed a
      significant correlation (Spearman rho: -0.2 to -0.4) between small initial bone
      height and a greater amount of apical bone gain. CONCLUSIONS: A gain in apical
      bone height can be expected if implants are placed in combination with ISL
      without graft material. Variability is high, however.

PMID- 23968309
TI  - Treatment of neonatal progressive ventricular dilatation: a single-centre
      experience.
AB  - OBJECTIVE: To describe our experience with a cohort of 295 infants with
      progressive ventricular dilatation occurring in the antenatal or neonatal period.
      METHODS: A search was performed in our cranial ultrasound database. All records
      and images of infants in whom an imaging diagnosis of progressive ventricular
      dilatation had been made were retrieved. In addition, modes of treatment were
      analysed. RESULTS: Between February 1991 and March 2012, 295 neonates were
      admitted to our level 3 neonatal intensive care unit (NICU), and developed
      progressive ventricular dilatation for which they required intervention. In the
      majority of these infants, progressive ventricular dilatation developed following
      IVH grade III or IV (240/295; 81%) of whom 214/240 (89%) were preterms. Temporary
      treatment with lumbar punctures and punctures from ventricular reservoirs was
      sufficient for the majority of the preterms. A ventricular reservoir was inserted
      in 216/295 infants (73%). The overall infection rate was low (6%). A
      ventriculoperitoneal shunt (VP shunt) was inserted in 32% of the whole cohort,
      revision within 3 months was necessary in 20%, and shunt-related infection
      occurred in 12%. CONCLUSIONS: This large, single-centre cohort study reports the
      management of progressive ventricular dilatation in newborn infants. We have
      shown that with our approach, complications stay within acceptable limits.

PMID- 23968310
TI  - Modular design of redox-responsive stabilizers for nanocrystals.
AB  - Many potent drugs are difficult to administer intravenously due to poor aqueous
      solubility. A common approach for addressing this issue is to process them into
      colloidal dispersions known as "nanocrystals" (NCs). However, NCs possess high
      energy surfaces that must be stabilized with surfactants to prevent aggregation.
      An optimal surfactant should have high affinity for the nanocrystal's surface to
      stabilize it, but may also include a trigger mechanism that could offer the
      possibility of altering size distribution and uptake of the NC. This study
      presents a modular and systematic strategy for optimizing the affinity of
      polymeric stabilizers for drug nanocrystals both before and after oxidation
      (i.e., the selected trigger), thus allowing for the optimal responsiveness for a
      given application to be identified. A library of 10 redox-responsive polymer
      stabilizers was prepared by postpolymerization modification, using the thiol-yne
      reaction, of two parent block copolymers. The stabilizing potential of these
      polymers for paclitaxel NCs is presented as well as the influence of oxidation on
      size and dissolution following exposure to reactive oxygen species (ROS), which
      are strongly associated with chronic inflammation and cancer. Owing to the
      versatility of postpolymerization modification, this contribution provides
      general tools for preparing triggered-sheddable stabilizing coatings for
      nanoparticles. 

PMID- 23968311
TI  - The role of an Aboriginal women's group in meeting the high needs of clients
      attending outpatient alcohol and other drug treatment.
AB  - INTRODUCTION AND AIMS: Support groups are typically offered as part of specialist
      alcohol or other drug treatment. However, their usefulness with Indigenous
      Australians has not been examined. This paper provides a profile of Aboriginal
      women attending an inner city outpatient alcohol and other drug treatment
      service, insight into how effective women and staff perceive the support group to
      be at meeting their needs and suggestions for improvements. DESIGN AND METHODS:
      Structured interviews were conducted with 24 Aboriginal female clients of an
      outpatient treatment service and with 21 staff from across that service and the
      local Aboriginal Medical Service. Client interviews also assessed alcohol
      consumption and mental health risk (Indigenous Risk Impact Screen). RESULTS:
      Clients reported social and health indicators illustrating disadvantage and
      complex needs. Most clients and staff perceived the group to be useful and easily
      accessible. The participants discussed positive elements including opportunities
      for shared experience in a non-judgemental environment, practical support and
      health education. Staff reported how the safe, relaxed environment of the group
      helped with early identification of issues and user-friendly pathways for
      treatment access. Suggested improvements included greater involvement from
      Aboriginal staff and community members and enhanced communication with other
      staff. DISCUSSION AND CONCLUSIONS: Clients and staff recognised the usefulness of
      the group, including the opportunities it provided for socialisation and early
      intervention. Comprehensive research is needed to determine the types and sources
      of support that best assist Aboriginal women with substance use disorders.

PMID- 23968312
TI  - Evaluation of the acceptability of Peer Physical Examination (PPE) in medical and
      osteopathic students: a cross sectional survey.
AB  - BACKGROUND: Peer physical examination (PPE) is a method of training in medical
      and osteopathic curricula. The aim of this study was to compare the acceptability
      of PPE in two classes of medical and osteopathic students after their first
      experience, to obtain comparative information useful for an understanding of the
      different professional approaches. The leading hypothesis was that osteopathic
      students enter the curriculum with a more positive attitude to bodily contact.As
      a secondary aim, this study validated the new version of a questionnaire to
      assess the acceptability of PPE. METHODS: A new version of a previously validated
      questionnaire and an instrument from the literature (the Examining Fellow Student
      [EFS] questionnaire) were used for a cross-sectional survey in a class of 129 3rd
      year medical students and in two parallel classes of 1st year osteopathic
      students (total of 112 students). RESULTS: The mean score of the new
      questionnaire was significantly higher for the osteopathic students than for the
      medical students (53.4 +/- 6.3 vs. 43.4 +/- 8.9; p < 0.01). The only independent
      variables that were significantly predictive of the score in a linear regression
      analysis were gender and the condition of medical or osteopathic student. The EFS
      mean score also showed a significant difference between the osteopathic and
      medical students (30.76 +/- 2.9 vs. 27.85 +/- 4.3; p < 0.01).Factor analysis of
      the new questionnaire identified three factors (appropriateness and usefulness,
      sexual implications and passive role) accounting for 62.8% of the variance.
      Criterion validity was assessed by correlation with the EFS (Pearson's r
      coefficient = 0.61). Reliability was expressed in terms of Cronbach's alpha
      coefficient, which equals 0.86. CONCLUSIONS: These quantitative results are
      consistent with previous qualitative research on the process of embodiment both
      in medicine and osteopathy. The new questionnaire proved to be valid and
      reliable. The objective assessment of the acceptability of PPE is a way to
      determine differences in students' attitudes towards contact with the body and
      can be used for counselling students regarding career choice. This study can also
      highlight differences between students from different professions and serve as a
      basis for reflection for improved mutual interprofessional understanding and
      future interprofessional education.

PMID- 23968313
TI  - Integrating palliative care in the out-of-hospital setting: four things to jump
      start an EMS-palliative care initiative.
AB  - Emergency medical service (EMS) is frequently called to care for a seriously ill
      patient with a life-threatening or life-limiting illness. The seriously ill
      include both the acutely injured patients (for example in mass casualty events)
      and those who suffer from advanced stages of a chronic disease (for example
      severe malignant pain). EMS therefore plays an important role in delivering
      realistic, appropriate, and timely care that is consistent with the patient's
      wishes and in treating distressing symptoms in those who are seriously ill. The
      purpose of this article is to; 1) review four case scenarios that relate to
      palliative care and may be commonly encountered in the out-of-hospital setting
      and 2) provide a road map by suggesting four things to do to start an EMS
      palliative care initiative in order to optimize out-of-hospital care of the
      seriously ill and increase preparedness of EMS providers in these difficult
      situations.

PMID- 23968314
TI  - Ring-shaped Re(I) multinuclear complexes with unique photofunctional properties.
AB  - We synthesized for the first time a series of emissive ring-shaped Re(I)
      complexes (Re-rings) with various numbers of Re(I) units and various lengths of
      bridge ligands. The photophysical properties of the Re-rings could be varied
      widely through changes in the size of the central cavity. A smaller central
      cavity of the Re-rings induced intramolecular pi-pi interactions between the
      ligands and consequently caused a stronger emission and a longer lifetime of the
      excited state. The Re-rings can function as efficient and durable
      photosensitizers. The combination of a trinuclear Re-ring photosensitizer with
      fac-[Re(bpy)(CO)3(MeCN)](+) (bpy = 2,2'-bipyridine) as a catalyst photocatalyzed
      CO2 reduction with the highest quantum yield of 82%. 

PMID- 23968315
TI  - Current trends in leprosy transmission in eastern India in the era of 12-month
      multi-drug treatment: a hospital-based retrospective study.
AB  - OBJECTIVES: Our objective was to study current trends in the occurrence of new
      cases of leprosy (Hansen's disease [HD]) a decade after significant operational
      changes in the National Leprosy Elimination Program (NLEP) were enacted by
      shortening the duration of multi-drug treatment for multibacillary cases of HD to
      12 months and stopping post-treatment follow-up. METHODS: The percentages
      represented by newly diagnosed cases of HD among all new patients attending the
      dermatology outpatient department (OPD) from April 2008 to March 2011 were
      calculated from hospital records. Patient age and sex, and type of disease were
      noted in each case, and annual data were compared. The OPD data were also matched
      with population data for the catchment area of the hospital (i.e. the South 24
      Parganas district). RESULTS: There was a slight annual decline in the percentage
      of new cases represented by HD, but this was not statistically significant. This
      trend broadly corroborated changes in the annual new case detection rate in the
      catchment area of the hospital. In addition, the percentage of HD cases
      represented by paucibacillary disease was significantly higher than that
      represented by multibacillary HD (P=0.0072). CONCLUSIONS: To the best of our
      knowledge, this is the first study of this type to be conducted in eastern India.
      The present data indicate that significant transmission of HD is ongoing in the
      community.

PMID- 23968316
TI  - Oral anticoagulation and self-management: analysis of the factors that determine
      the feasibility of using self-testing and self-management in primary care.
AB  - BACKGROUND: The skills of patients on oral anticoagulants are critical for
      achieving good outcomes with this treatment. Self-management, or the capacity of
      patients to control their INR level and adjust their treatment, is an effective
      strategy of treatment. Capacity of patients to self manage is determined by a
      range of factors. The identification of these factors would improve the design of
      self management programmes and in turn increase the number of patients able to
      self-manage. The objective of our study is to identify those factors that
      determine the ability of patients on oral anticoagulant therapy to achieve self
      management of their treatment. DESIGN: This will be a three year quasi-
      experimental prospective study with a control group. 333 patients on
      anticoagulant therapy from five health centres of the Basque Health Service are
      to be followed up for a period of six months each after the intervention, to
      assess their ability to self-test and self-manage. The intervention will consist
      of a patient training programme involving the provision of information and
      practical training concerning their condition and its treatment, as well as how
      to use a portable blood coagulation monitoring device and adjust their
      anticoagulant dose. DISCUSSION: The ease-of-use of this technique lead us to
      believe that self-management is feasible and will represent an innovative advance
      that should have a substantial impact on the quality of life of this patients and
      their families as well as on the health care provision systems. TRIAL
      REGISTRATION: Osakidetza Protocol Record ISCIII-11/02285, Oral anticoagulation
      and self-management, ClinicalTrials.gov Identifier: NCT01878539.

PMID- 23968317
TI  - Twelve tips on setting up a new medical school.
AB  - BACKGROUND: Not many set up a new medical school, so those that do usually do it
      only once. Thus most have no personal previous experience to guide them. AIM: To
      give those setting up a new school some broad issues to think about as they set
      about their task. METHODS: The tips were derived from personal experience in the
      UK and in Africa. RESULTS: The 12 tips identified are engage closely with the
      parent university from the outset; decide what the medical school is going to
      concentrate on first; agree on the overall aim of the school; decide who 'owns'
      the course; agree on the type of pedagogy to be employed; ensure good alignment
      between the aims, outcomes, learning framework and assessment; plan the
      assessment along with the rest of the course; make sure the school facilities are
      sufficient and appropriate to support the aims of the course; appoint the right
      staff; plan the research programme early; plan the co-ordination between the
      university and the health services at all levels; communicate, communicate,
      communicate. CONCLUSION: It is hoped that these suggestions will be widely
      applicable to different contexts and assist those in the exciting task of setting
      up a new school.

PMID- 23968318
TI  - Developing cross-cultural competence in Chinese medical students.

PMID- 23968319
TI  - The hidden curriculum: are medical students adequately prepared for life on the
      wards?

PMID- 23968320
TI  - Deaf awareness training in medical schools.

PMID- 23968321
TI  - Are we missing a trick?

PMID- 23968323
TI  - The Objective Structured Clinical Examination (OSCE): AMEE Guide No. 81. Part I:
      an historical and theoretical perspective.
AB  - The Objective Structured Clinical Examination (OSCE) was first described by
      Harden in 1975 as an alternative to the existing methods of assessing clinical
      performance (Harden et al. 1975). The OSCE was designed to improve the validity
      and reliability of assessment of performance, which was previously assessed using
      the long case and short case examinations. Since then the use of the OSCE has
      become widespread within both undergraduate and postgraduate clinical education.
      We recognise that the introduction of the OSCE into an existing assessment
      programme is a challenging process requiring a considerable amount of theoretical
      and practical knowledge. The two parts of this Guide are designed to assist all
      those who intend implementing the OSCE into their assessment systems. Part I
      addresses the theoretical aspects of the OSCE, exploring its historical
      development, its place within the range of assessment tools and its core
      applications. Part II offers more practical information on the process of
      implementing an OSCE, including guidance on developing OSCE stations, choosing
      scoring rubrics, training examiners and standardised patients and managing
      quality assurance processes. Together we hope these two parts will act as a
      useful resource both for those choosing to implement the OSCE for the first time
      and also those wishing to quality assure their existing OSCE programme. 

PMID- 23968324
TI  - The Objective Structured Clinical Examination (OSCE): AMEE Guide No. 81. Part II:
      organisation & administration.
AB  - The organisation, administration and running of a successful OSCE programme need
      considerable knowledge, experience and planning. Different teams looking after
      various aspects of OSCE need to work collaboratively for an effective question
      bank development, examiner training and standardised patients' training. Quality
      assurance is an ongoing process taking place throughout the OSCE cycle. In order
      for the OSCE to generate reliable results it is essential to pay attention to
      each and every element of quality assurance, as poorly standardised patients,
      untrained examiners, poor quality questions and inappropriate scoring rubrics
      each will affect the reliability of the OSCE. The validity will also be
      influenced if the questions are not realistic and mapped against the learning
      outcomes of the teaching programme. This part of the Guide addresses all these
      important issues in order to help the reader setup and quality assure their new
      or existing OSCE programmes. 

PMID- 23968325
TI  - Residents provide feedback to their clinical teachers: reflection through
      dialogue.
AB  - BACKGROUND: Physicians play a crucial role in teaching residents in clinical
      practice. Feedback on their teaching performance to support this role needs to be
      provided in a carefully designed and constructive way. AIMS: We investigated an
      evaluation system for evaluating supervisors and providing formative feedback.
      METHOD: In a design based research approach, the 'Evaluation and Feedback For
      Effective Clinical Teaching System' (EFFECT-S) was examined by conducting semi
      structured interviews with residents and supervisors of five departments in five
      different hospitals about feedback conditions, acceptance and its effects.
      Interviews were analysed by three researchers, using qualitative research
      software (ATLAS-Ti). RESULTS: Principles and characteristics of the design are
      supported by evaluating EFFECT-S. All steps of EFFECT-S appear necessary. A new
      step, team evaluation, was added. Supervisors perceived the feedback as
      instructive; residents felt capable of providing feedback. Creating safety and
      honesty require different actions for residents and supervisors. Outcomes include
      awareness of clinical teaching, residents learning feedback skills, reduced
      hierarchy and an improved learning climate. CONCLUSIONS: EFFECT-S appeared useful
      for evaluating supervisors. Key mechanism was creating a safe environment for
      residents to provide honest and constructive feedback. Residents learned
      providing feedback, being part of the CanMEDS and ACGME competencies of medical
      education programmes.

PMID- 23968326
TI  - Boosting and rescuing epidermal superior population from fresh keratinocyte
      cultures.
AB  - Epidermal stem cells (EpSCs) hold great expectations in a regenerative medicine
      context, but innovative methods that permit to obtain a significant yield of
      EpSCs or stem-like epidermal cells are still required. We propose a two-step
      strategy to obtain a superior epidermal stem-like cell fraction among primary
      keratinocytes (KCs) isolated from adult human skin. The approach is based on the
      combination of rapid adherence to collagen IV with the rock-associated kinase
      inhibitor (ROCKi) treatment, and the subsequent immunomagnetic separation of the
      alpha6(high)/CD71(dim) cell subset. The combined collagen IV and ROCKi treatment
      showed not only to enhance cells clonogenic capacity, but also to induce an early
      epidermal phenotypic signature, along with the diminished expression of late
      differentiation-associated markers. More importantly, collagen IV and the ROCKi
      efficiently promoted a synergized effect over alpha6(high)/CD71(dim) expression,
      boosting the number of highly proliferative KCs stem-like cells as demonstrated
      by the expression of ki67. This cell fraction showed a superior ability to
      generate a 3D stratified epithelium formed by cells with successive
      differentiation phenotypes. Overall, this strategy indulged the possibility to
      uncover, among adult KCs, a superior epidermal cell population with stem-like
      proliferation capacity and early differentiation degree to be used in numerous
      skin regeneration approaches. 

PMID- 23968327
TI  - Glycaemic threshold for activation of the stress response in children.

PMID- 23968328
TI  - Acute myeloid leukemia in a 38-year-old hemodialyzed patient with von Hippel
      Lindau disease.
AB  - Von Hippel-Lindau disease (VHL disease) is a hereditary cancer predisposition
      syndrome caused by mutations of the von Hippel-Lindau tumor suppressor gene. The
      gene product, pVHL, regulates the level of proteins that play a central role in
      protecting cells against hypoxia. Clinical hallmarks of von Hippel-Lindau disease
      are the development of central nervous system hemangioblastomas, renal cell
      carcinoma, pheochromocytoma, neuroendocrine tumors and endolymphatic sac
      tumors.In this article the case of a 38-year old hemodialyzed patient who became
      ill with acute myeloid leukemia (AML) three years after being diagnosed with von
      Hippel-Lindau disease is presented.After cytostatic treatment the patient went
      into complete hematologic remission but there was still residual disease at the
      genetic level. After consolidation therapy patient developed bone marrow aplasia
      and severe pneumonia. Despite intensive treatment the patient died from acute
      respiratory failure.In this paper we present for the first time a case of von
      Hippel-Lindau disease associated with acute myeloid leukemia. No evidence of
      relationship between VHL disease and blood cancers has been demonstrated so far.
      Despite the fact that there is an increased risk of cancer development in
      hemodialyzed patients, cancer is a relatively rare cause of death in the dialysed
      population, and the most common malignancies are genitourinary cancers. It seems
      likely that development of acute myeloid leukemia in patient with VHL disease can
      be related to epigenetic alterations of the VHL gene, but further studies are
      needed. 

PMID- 23968329
TI  - Expansion of the Kell blood group system: two new high-prevalence antigens and
      two novel K0 (Kellnull ) phenotypes.
AB  - BACKGROUND: The number of KEL alleles associated with new antigens or loss of
      expression of high-prevalence antigens continues to increase. We investigated KEL
      in five samples: two with K0 (null) phenotypes and three with normal Kell
      expression and antibodies to high-prevalence antigens. STUDY DESIGN AND METHODS:
      Red blood cell (RBC) typing and antibody identification were by standard methods.
      Genomic DNA was isolated from white blood cells and DNA array testing and
      sequencing of KEL exons was performed by standard methods. RESULTS: Proband 1, an
      Asian woman with Kp(b+) RBCs, presented with alloanti-Kp(b) . Four years later,
      the antibody was reactive with all RBCs except K0 . She was homozygous for KEL
      c.877C>T change (p.Arg293Trp), and the high-prevalence antigen absent from her
      RBCs was named KHUL. Probands 2 and 3, both Japanese and homozygous for KEL
      c.875G>A (p.Arg292Gln), presented with an antibody reactive with all except K0
      RBCs. The antibody, named KYOR, recognizes an antigen antithetical to KYO
      (KEL31). Proband 4, a pregnant Middle Eastern woman, presented with alloanti
      Kp(b) , but her RBCs did not express Kell antigens. She was homozygous for KEL
      c.230G>T (p.Cys77Phe). Proband 5, a multiply transfused Caucasian female with an
      antibody reactive with all RBCs except K0 and lacking Kell antigens, was a
      compound heterozygote carrying a silenced allele c.574C>T (p.Arg192Stop) in trans
      to c.1664G>A (p.Gly555Glu). CONCLUSION: We describe two new high-prevalence Kell
      antigens, KHUL (ISBT 006037; KEL37) and KYOR (ISBT 006038; KEL38), and two novel
      alleles encoding K0 phenotypes. We caution that antibodies produced by
      individuals with K0 RBCs or lacking high-prevalence antigens can present as anti
      Kp(b) .

PMID- 23968330
TI  - Molecular characterization of echovirus 30-associated outbreak of aseptic
      meningitis in Guangdong in 2012.
AB  - BACKGROUND: Evaluation of the primary etiologic agents that cause aseptic
      meningitis outbreaks may provide valuable information regarding the prevention
      and management of aseptic meningitis. An outbreak of aseptic meningitis occurred
      from May to June, 2012, in Guangdong Province, China. In order to determine the
      etiologic agent, CSF specimens from 121 children hospitalized for aseptic
      meningitis at Luoding People's Hospital of Guangdong Province were tested for
      virus isolation and identification. RESULTS: Enterovirus RNA was positive in
      62.0% of 121 CSF sspecimens by real-time polymerase chain reaction (RT-PCR).
      Amplification and sequencing of the VP1 region of enterovirus isolates revealed
      Echovirus 30 (E30) was the most common isolated serotype (80% of 40 enterovirus
      strains).For the molecular characterization of the E30 isolates, the VP1 gene
      sequence of 20 Luoding E30 isolates was compared pairwise using the MegAlign with
      reference strains from GenBank. The pairwise comparison of the nucleotide
      sequences of the VP1 genes demonstrated that the sequences of the strains
      differed from those of lineage groups C, D, E, F, and G. Reconstruction of the
      phylogenetic tree based on the VP1 nucleotide sequences resulted in a
      monophyletic tree, with seven clustered lineage groups. Most of the isolates were
      segregated from other lineage groups. Four E30 isolates causing this outbreak
      aggregated into the Lineage A cluster which was derived from E30 strains that
      circulated in other regions of China from 2003-2010. CONCLUSIONS: This study
      demonstrated the Luoding strains were a distinct lineage of E30, and a probable
      cause of this outbreak. The study also demonstrated that different E30 variants
      existed in the local meningitis outbreak.

PMID- 23968331
TI  - Development of an atmospheric pressure ion mobility spectrometer-mass
      spectrometer with an orthogonal acceleration electrostatic sector TOF mass
      analyzer.
AB  - Recently developed ion mobility mass spectrometer is described. The instrument is
      based on a drift tube ion mobility spectrometer and an orthogonal acceleration
      electrostatic sector time-of-flight mass analyzer. Data collection is performed
      using a specially developed fast ADC-based recorder that allows real-time data
      integration in an interval between 3 and 100 s. Primary tests were done with
      positive ion electrospray. The tests have shown obtaining 100 ion mobility
      resolving power and 2000 mass resolving power. Obtained for 2,6-di-tert
      butylpyridine in electrosprayed liquid samples during 100 s analysis and full
      IMS/MS data collection mode were 4 nM relative limits of detection and a 1 pg
      absolute limit of detection (S/N=3). Characteristic ion mobility/mass
      distributions were recorded for selected antibiotics, including amoxicillin,
      ampicillin, lomefloxacin, and ofloxacin. At studied conditions, lomefloxacin
      forms only a protonated molecule-producing reduced ion mobility peak at 1.082
      cm(2)/(V s). Both amoxicillin and ampicillin produce [M + H](+), [M + CH3OH +
      H](+), and [M + CH3CN + H](+). Amoxicillin shows two peaks at 0.909 cm(2)/(V s)
      and 0.905 cm(2)/(V s). Ampicillin shows one peak at 0.945 cm(2)/(V s). Intensity
      of protonated methanol containing cluster for both ampicillin and amoxicillin has
      a clear tendency to rise with sample keeping time. Ofloxacin produces two peaks
      in the ion mobility distribution. A lower ion mobility peak at 1.051 cm(2)/(V s)
      is shown to be formed by [M + H](+) ions. A higher ion mobility peak appearing
      for samples kept more than 48 h is shown to be formed by both [M + H](+) ion and
      a component identified as the [M + 2H + M](+2) cluster. The cluster probably
      partly dissociates in the interface producing the [M + H](+) ion. 

PMID- 23968333
TI  - From germinal matrix to cerebellar haemorrhage.
AB  - For many years cerebellar development after preterm birth has been poorly
      investigated and has been studied without taking germinal matrix-intraventricular
      haemorrhage into account. Advanced neuroimaging techniques like magnetic
      resonance imaging, as well as the use of various acoustic windows (mastoid
      fontanelle, occipital foramen) have allowed for in vivo diagnosis of acquired
      focal haemorrhagic lesions in the cerebellum of very preterm babies. The
      vulnerability of the cerebellum also seems to be related to specific gestational
      ages, i.e., between 23 and 27 weeks, when rapid growth in cerebellar volume
      occurs and at a much faster rate than mean brain volume increase. In this paper,
      the contribution of the cerebellum in long-term motor cognitive, learning and
      behavioural functions, including psychiatric ones, is discussed. 

PMID- 23968334
TI  - Toward quantitative electrochemical measurements on the nanoscale by scanning
      probe microscopy: environmental and current spreading effects.
AB  - The application of electric bias across tip-surface junctions in scanning probe
      microscopy can readily induce surface and bulk electrochemical processes that can
      be further detected though changes in surface topography, Faradaic or conductive
      currents, or electromechanical strain responses. However, the basic factors
      controlling tip-induced electrochemical processes, including the relationship
      between applied tip bias and the thermodynamics of local processes, remains
      largely unexplored. Using the model Li-ion reduction reaction on the surface in
      Li-ion conducting glass ceramic, we explore the factors controlling Li-metal
      formation and find surprisingly strong effects of atmosphere and back electrode
      composition on the process. We find that reaction processes are highly dependent
      on the nature of the counter electrode and environmental conditions. Using a
      nondepleting Li counter electrode, Li particles could grow significantly larger
      and faster than a depleting counter electrode. Significant Li ion depletion leads
      to the inability for further Li reduction. Time studies suggest that Li diffusion
      replenishes the vacant sites after ~12 h. These studies suggest the feasibility
      of SPM-based quantitative electrochemical studies under proper environmental
      controls, extending the concepts of ultramicroelectrodes to the single-digit
      nanometer scale. 

PMID- 23968332
TI  - Multicenter validation of urinary CXCL9 as a risk-stratifying biomarker for
      kidney transplant injury.
AB  - Noninvasive biomarkers are needed to assess immune risk and ultimately guide
      therapeutic decision-making following kidney transplantation. A requisite step
      toward these goals is validation of markers that diagnose and/or predict relevant
      transplant endpoints. The Clinical Trials in Organ Transplantation-01 protocol is
      a multicenter observational study of biomarkers in 280 adult and pediatric first
      kidney transplant recipients. We compared and validated urinary mRNAs and
      proteins as biomarkers to diagnose biopsy-proven acute rejection (AR) and
      stratify patients into groups based on risk for developing AR or progressive
      renal dysfunction. Among markers tested for diagnosing AR, urinary CXCL9 mRNA
      (odds ratio [OR] 2.77, positive predictive value [PPV] 61.5%, negative predictive
      value [NPV] 83%) and CXCL9 protein (OR 3.40, PPV 67.6%, NPV 92%) were the most
      robust. Low urinary CXCL9 protein in 6-month posttransplant urines obtained from
      stable allograft recipients classified individuals least likely to develop future
      AR or a decrement in estimated glomerular filtration rate between 6 and 24 months
      (92.5-99.3% NPV). Our results support using urinary CXCL9 for clinical decision
      making following kidney transplantation. In the context of acute dysfunction, low
      values can rule out infectious/immunological causes of injury. Absent urinary
      CXCL9 at 6 months posttransplant defines a subgroup at low risk for incipient
      immune injury.

PMID- 23968335
TI  - Aboriginal people in remote communities in Arnhem Land (Northern Territory)
      restrict their smoking in some environments: Implications for developing and
      implementing interventions to reduce exposure to environmental tobacco smoke.
AB  - INTRODUCTION AND AIMS: In Arnhem Land's remote Aboriginal communities [Northern
      Territory], very high smoking rates and overcrowding mean high exposure to
      Environmental Tobacco Smoke. This study compared smokers who restrict their
      smoking in these environments with those who do not. DESIGN AND METHODS: In 2008
      2009, 258 smokers (137 males and 121 females) aged >= 16 years, provided
      information permitting categorisation of those who 'RESTRICT' their smoking in
      the house, car or workplace from those who do 'NOT RESTRICT'. Univariable and
      multivariable logistic regressions compared 'RESTRICT' and 'NOT RESTRICT' groups
      by gender, age group, daily use, tobacco consumption, time-to-first-cigarette and
      quit intentions. Those in the 'RESTRICT' group explained their motivations,
      summarised using qualitative data analysis. RESULTS: Men were almost twice as
      likely to 'NOT RESTRICT' their smoking (odds ratio = 1.88, 95% confidence
      interval = 1.14-3.08, P = 0.013). Time-to-first-cigarette was the strongest
      predictor to 'NOT RESTRICT' in women (odds ratio = 3.48, 95% confidence interval
      = 1.44-8.41, P = 0.006) with daily consumption the strongest predictor in men
      (odds ratio = 3.15, 95% confidence interval = 1.39-7.18, P = 0.006). Men and
      women shared similar motivations for restricting smoking. DISCUSSION AND
      CONCLUSIONS: Smoke-free homes and workplaces are important opportunities to
      reduce exposure to Environmental Tobacco Smoke in remote Indigenous communities.

PMID- 23968336
TI  - Attitudes towards homeless people among emergency department teachers and
      learners: a cross-sectional study of medical students and emergency physicians.
AB  - BACKGROUND: Medical students' attitudes and beliefs about homeless people may be
      shaped by the attitudes of their teachers and one of the most common sites for
      learning about homeless patients is the emergency department. The objective of
      this study was to determine if medical students in the preclinical and clinical
      years and emergency medicine faculty and residents have different attitudes and
      beliefs about homeless people. METHODS: The Health Professional Attitudes Toward
      the Homeless Inventory (HPATHI), was administered to all medical students, and
      emergency medicine physicians and residents at a large academic health sciences
      center in Canada. The HPATHI examines attitudes, interest and confidence on a 5
      point Likert scale. Differences among groups were examined using the Kruskal
      Wallis test and Pearson's chi-square test. RESULTS: The HPATHI was completed by
      371 individuals, for an overall response rate of 55%. Analysis of dichotomized
      median and percentage results revealed 5/18 statements were significant by both
      methods. On the attitudes subscales physicians and residents as a group were more
      negative for 2/9 statements and on the confidence subscale more positive for 1/4
      statements. The interest subscale achieved overall statistical significance with
      decreased positive responses among physicians and residents compared to medical
      students in 2/5 statements. CONCLUSION: This study revealed divergences in
      attitudes, interests and beliefs among medical students and emergency medicine
      physicians and residents. We offer strategies for training interventions and
      systemic support of emergency faculty. Emergency medicine physicians can examine
      their role in the development of medical students through both formal and
      informal teaching in the emergency department.

PMID- 23968337
TI  - The iTClamp controls junctional bleeding in a lethal swine exsanguination model.
AB  - OBJECTIVE: Severe hemorrhage is a leading cause of death and difficult to control
      even by trained medical personnel. Current interventions have significant
      limitations in the prehospital setting; therefore, a need exists for a new and
      effective treatment. iTraumaCare has designed a temporary wound closure device,
      the iTClamp, which controls external hemorrhage from open wounds within
      compressible zones. The device approximates the wound edges, sealing the skin
      within a pressure bar, enabling creation of a hematoma and subsequent clot
      formation. The objective of this study is to test the effectiveness of the
      iTClamp to control external bleeding due to a major vascular injury to the groin
      in an in vivo swine model. METHODS: Twenty Yorkshire-cross male swine were
      enrolled in this study. A complex groin injury was created by complete excision
      of the femoral artery and vein along with some surrounding muscle. The animals
      were divided into four treatment groups: control (no treatment), early iTClamp
      treatment, late iTClamp treatment, and standard gauze treatment. Survival rate,
      survival time, and blood loss were the primary endpoints. Physiologic parameters
      (heart rate, blood pressure, oxygen saturation) were monitored throughout the
      experiment and blood samples were collected to analyze partial thromboplastin
      time and fibrinogen. RESULTS: All (100%) of the animals treated with the iTClamp
      lived through the end of the experiment, compared to 60% in standard gauze
      treated and 0% of untreated control animals (early and late iTClamp vs. control
      and standard gauze, Fisher's exact, p = 0.003). Both the early iTClamp and late
      iTClamp treatment groups survived significantly longer than the untreated control
      pigs (Mann-Whitney U-test, p < 0.009). External blood loss was significantly
      lower in animals treated with the iTClamp (early) compared to no treatment (Mann
      Whitney U-test, p < 0.008). There was no significant change in physiologic or
      hematologic parameters between treatment groups. CONCLUSIONS: The iTClamp showed
      statistically significant improvement in survival, survival time, and estimated
      blood loss when compared to no treatment. This proof-of-concept study
      demonstrates the potential of the iTClamp to control severe bleeding and prevent
      blood loss.

PMID- 23968338
TI  - Atomic imaging of the irreversible sensing mechanism of NO2 adsorption on copper
      phthalocyanine.
AB  - Ambient NO2 adsorption onto copper(II) phthalocyanine (CuPc) monolayers is
      observed using ultrahigh vacuum (UHV) scanning tunneling microscopy (STM) to
      elucidate the molecular sensing mechanism in CuPc chemical vapor sensors. For low
      doses (1 ppm for 5 min) of NO2 at ambient temperatures, isolated chemisorption
      sites on the CuPc metal centers are observed in STM images. These chemisorbates
      almost completely desorb from the CuPc monolayer after annealing at 100  degrees
      C for 30 min. Conversely, for high NO2 doses (10 ppm for 5 min), the NO2 induces
      a fracture of the CuPc domains. This domain fracture can only be reversed by
      annealing above 150  degrees C, which is consistent with dissociative
      chemisorption into NO and atomic O accompanied by surface restructuring. This
      high stability implies that the domain fracture results from tightly bound
      adsorbates, such as atomic O. Existence of atomic O on or under the CuPc layer,
      which results in domain fracture, is revealed by XPS analysis and ozone-dosing
      experiments. The observed CuPc domain fracturing is consistent with a mechanism
      for the dosimetric sensing of NO2 and other reactive gases by CuPc organic thin
      film transistors (OTFTs). 

PMID- 23968339
TI  - Clinical efficacy and compliance of sublingual immunotherapy with
      Dermatophagoides farinae drops in patients with atopic dermatitis.
AB  - BACKGROUND: The oral route for administration of allergen immunotherapy has been
      explored since the 1900s. We attempted to evaluate the efficacy and safety of
      sublingual immunotherapy (SLIT) with Dermatophagoides farinae drops in patients
      with atopic dermatitis (AD) and investigate related factors influencing the
      patients' compliance. METHODS: A total of 107 patients with AD were randomized to
      receive either D. farinae drops plus pharmacotherapy (treatment group, n = 58) or
      only pharmacotherapy (control group, n = 49). Patients' compliance, the total
      effective rate, daily drug scores, visual analogue scale (VAS) scores, and IgG4
      level were compared respectively between two groups at different time points.
      RESULTS: Twenty-three cases have withdrawn from the study. The total effective
      rate in the treatment group (77.78%) was significantly higher than the control
      group (53.85%) (P < 0.05). The treatment group was significantly reduced in daily
      drug scores and VAS scores compared with the control group at 12 months follow
      up. Meanwhile, at the end of therapy, a significant difference was found in the
      change in average daily drug scores (difference from 1 month) between two groups
      (P < 0.01); The treatment group evidently had a higher level of serum-specific
      IgG4 than the control group at 6 and 12 month of treatment (P < 0.05).
      CONCLUSION: Dermatophagoides farinae drops are a safe and effective SLIT for
      patients with AD, which was proven to reduce the need for medicine. In addition,
      SLIT could induce a tolerogenic IgG4 response to mite allergen correlated with
      favorable clinical efficacy. Standardization of specific immunotherapy is
      essential to ensure therapeutic efficacy and compliance.

PMID- 23968341
TI  - Discovery of peptides and proteins with biotechnological potential: from methods
      to application.

PMID- 23968340
TI  - Evaluation of a self-management patient education program for patients with
      chronic heart failure undergoing inpatient cardiac rehabilitation: study protocol
      of a cluster randomized controlled trial.
AB  - BACKGROUND: Chronic heart failure requires a complex treatment regimen on a life
      long basis. Therefore, self-care/self-management is an essential part of
      successful treatment and comprehensive patient education is warranted. However,
      specific information on program features and educational strategies enhancing
      treatment success is lacking. This trial aims to evaluate a patient-oriented and
      theory-based self-management educational group program as compared to usual care
      education during inpatient cardiac rehabilitation in Germany. METHODS/DESIGN: The
      study is a multicenter cluster randomized controlled trial in four cardiac
      rehabilitation clinics. Clusters are patient education groups that comprise HF
      patients recruited within 2 weeks after commencement of inpatient cardiac
      rehabilitation. Cluster randomization was chosen for pragmatic reasons, i.e. to
      ensure a sufficient number of eligible patients to build large-enough educational
      groups and to prevent contamination by interaction of patients from different
      treatment allocations during rehabilitation. Rehabilitants with chronic systolic
      heart failure (n = 540) will be consecutively recruited for the study at the
      beginning of inpatient rehabilitation. Data will be assessed at admission, at
      discharge and after 6 and 12 months using patient questionnaires. In the
      intervention condition, patients receive the new patient-oriented self-management
      educational program, whereas in the control condition, patients receive a short
      lecture-based educational program (usual care). The primary outcome is patients'
      self-reported self-management competence. Secondary outcomes include behavioral
      determinants and self-management health behavior (symptom monitoring, physical
      activity, medication adherence), health-related quality of life, and treatment
      satisfaction. Treatment effects will be evaluated separately for each follow-up
      time point using multilevel regression analysis, and adjusting for baseline
      values. DISCUSSION: This study evaluates the effectiveness of a comprehensive
      self-management educational program by a cluster randomized trial within
      inpatient cardiac rehabilitation in Germany. Furthermore, subgroup-related
      treatment effects will be explored. Study results will contribute to a better
      understanding of both the effectiveness and mechanisms of a self-management group
      program as part of cardiac rehabilitation. TRIAL REGISTRATION: German Clinical
      Trials Register: DRKS00004841; WHO International Clinical Trials: = DRKS00004841.

PMID- 23968342
TI  - Magnetic nanoparticles: new players in antimicrobial peptide therapeutics.
AB  - Antimicrobial peptides are distributed in all forms of life presenting activity
      against bacteria, fungi, viruses, parasites and cancer. In spite of the
      tremendous potential of these molecules, very few of them have been successfully
      developed into therapeutics. The major problems associated with this new class of
      antimicrobials are molecule stability, toxicity in host cells and production
      cost. A novel strategy to overcome these obstacles is conjugation to
      nanomaterials. Magnetic nanoparticles have been widely studied in biomedicine due
      to their physicochemical properties. The conjugation of antimicrobial peptides to
      magnetic nanoparticles could combine the best properties of both, generating an
      improved antimicrobial nanoparticle. Here we provide an overview and discuss the
      potential application of magnetic nanoparticles conjugated to antimicrobial
      peptides in overcoming diseases. 

PMID- 23968343
TI  - Nanobiotechnology: an efficient approach to drug delivery of unstable
      biomolecules.
AB  - Biotechnology and nanotechnology are fields of science that can be applied
      together to solve a variety of biological issues. In the case of human health,
      biotechnology attempts to improve advances on the therapy against several
      diseases. Therapeutic peptides and proteins are promissory molecules for
      developing new medicines. Gene transfection and RNA interference have been
      considered important approaches for modern therapy to treat cancer and viral
      infections. However, because of their instability, these molecules alone cannot
      be used for in vivo application, since they are easily degraded or presenting a
      poor efficiency. Nanotechnology can contribute by the development of
      nanostructured delivery systems to increase the stability and potency of these
      molecules. Studies involving polymeric and magnetic nanoparticles, dendrimers,
      and carbon nanotubes have demonstrated a possibility to use these systems as
      vectors instead of the conventional viral ones, which present adverse effects,
      such as recombination and immunogenicity. This review presents some possibilities
      and strategies to efficiently delivery peptides, proteins, gene and RNA
      interference using nanotechnology approach. 

PMID- 23968344
TI  - Biomedical exploitation of self assembled peptide based nanostructures.
AB  - Nowadays, peptide based disease prevention is an important topic in biomedical
      science, which may radically change the traditional use of biomaterials and
      improve the life quality. Self-assembled nanostructured peptides have been
      receiving extreme attention in the drug delivery field due their high
      biocompatibility levels, better loading capacity, extended circulation and
      localization in required target site. This article focuses on the composition and
      synthesis of different forms of self-assembled peptide nanostructures as
      nanotubes, nanofibers, nanoparticles, nanotapes and nanogels. The most important
      properties for their self assembled mechanism and their biomedical applications
      are also discussed. Various potential applications of nanostructures peptide
      could be developed designed for therapeutic agent's delivery, biosensors,
      anticancerous and antimicrobial activities. 

PMID- 23968345
TI  - Heterologous production of peptides in plants: fusion proteins and beyond.
AB  - Recombinant DNA technology has allowed the ectopic production of proteins and
      peptides of different organisms leading to biopharmaceutical production in large
      cultures of bacterial, yeasts and mammalian cells. Otherwise, the expression of
      recombinant proteins and peptides in plants is an attractive alternative
      presenting several advantages over the commonly used expression systems including
      reduced production costs, easy scale-up and reduced risks of pathogen
      contamination. Different types of proteins and peptides have been expressed in
      plants, including antibodies, antigens, and proteins and peptides of medical,
      veterinary and industrial applications. However, apart from providing a proof of
      concept, the use of plants as platforms for heterologous protein and peptide
      production still depends on key steps towards optimization including the
      enhancement of expression levels, manipulation of post-transcriptional
      modifications and improvements in purification methods. In this review,
      strategies to increase heterologous protein and peptide stability and
      accumulation are discussed, focusing on the expression of peptides through the
      use of gene fusions. 

PMID- 23968346
TI  - Critical aspects to be considered prior to large-scale production of peptides.
AB  - Numerous peptides are available on the market as therapeutic drugs for regulating
      tumor growth, microorganism proliferation, immune response and/or metabolic
      disorders. Peptides are produced either by chemical synthesis or heterologous
      expression. Independent of the method chosen, there are challenges to
      transferring its production from the bench (~mg/L) to the industrial (~g/L)
      scale. Thus, the main scale-up pitfalls for the two methods of peptide production
      are reviewed here, including the advantages of each. Moreover, there will be a
      special focus on the main challenges for large-scale, heterologous production
      systems. Peptides that are currently available on the market are also described
      with an emphasis on how their process optimization has been designed in order to
      develop a cost-effective product. 

PMID- 23968347
TI  - Mechanistic aspects of peptide-membrane interactions determined by optical,
      dielectric and piezoelectric techniques: an overview.
AB  - Antimicrobial peptides (AMPs) have been isolated from a wide variety of organisms
      that include microorganisms, plants, insects, frogs and mammals. As part of the
      innate immune system expressed in many tissues, AMPs are able to provide
      protection against invasion of foreign microorganisms and exhibit a broad
      spectrum of activity against bacteria, fungi and/or virus. Non-AMPs cell
      penetrating peptides have been used as carriers for overcoming the membrane
      barrier and helping in the delivery of various molecules into the cell.
      Physicochemical peptide-lipid interactions studies can provide us with reliable
      molecular information about microbe defense response, including the elucidation
      of the prevailing mechanisms of its action, such as the barrel-stave, toroidal
      pore, carpet and detergent-like models. In this paper, we present an overview of
      the peptide-lipid mechanisms of interaction as well as discuss alternative
      techniques that could help to elucidate the peptides functionality. Quartz
      crystal microbalance (QCM), surface plasmon resonance (SPR) spectroscopy and
      electrochemical impedance spectroscopy (EIS) are useful techniques to investigate
      in details of the peptide-membrane interaction. The techniques here discussed
      could also offer specific and low-cost methods that can to shed some light over
      the different modes of action of AMPs, contributing to the development of drugs
      against infectious diseases. 

PMID- 23968348
TI  - Recent progress towards pharmaceutical applications of disulfide-rich cyclic
      peptides.
AB  - Cyclotides and conotoxins are two classes of disulfide-rich peptides that occur
      in plants and animals respectively and are the major focus of study in our
      laboratory. In the last three years there has been significant progress in
      studies of these two classes of compounds and in this article we provide an
      overview of the findings from our laboratory in this period. Highlights include
      the discovery of cyclotides in the Fabaceae and Solanaceae plant families,
      members of which are widely used in human nutrition, and the discovery of new
      classes of cyclotide precursors. These discoveries confirm the widespread
      distribution of cyclotides in the plant kingdom and the diversity of precursor
      proteins involved in their biosynthesis. Other studies have delineated the mode
      of action of naturally occurring cyclotides and have demonstrated the versatility
      of synthetic cyclotides as stable protein engineering frameworks, with
      applications in drug design. Conotoxins continue to be a rich source of
      inspiration for drug design programs, and we summarize here a range of recent
      studies from our laboratory focusing on the development of novel synthetic
      strategies and the delineation of structure-activity relationships. A major
      highlight was the development of an orally active cyclized conotoxin derivative
      that is highly efficacious in a rat model of neuropathic pain. Overall the
      studies described herein provide much encouragement for continuing efforts to
      develop peptides as drugs.

PMID- 23968349
TI  - Antimicrobial activity of defensins and defensin-like peptides with special
      emphasis on those from fungi and invertebrate animals.
AB  - Living organisms are in perpetual contact with pathogenic microbes, and in
      encounter with parasites and predators. In order to protect themselves, they
      produce a variety of antimicrobial proteins and peptides. One family of such
      protective or defensive proteins is known as defensins, characterized by a
      cationic character, a low molecular mass, and an abundance of cysteine residues.
      Defensins from mammals and plants have been succinctly reviewed by a number of
      experts in this ever-growing field. This review encompasses the defensin
      plectasin from the saprophytic fungus Pseudoplectania nigrella as well as
      defensins and defensin-like peptides from invertebrate animals such as jellyfish,
      sponges, nematodes, crustaceans, arachnids, insects, bivalves, snails, and sea
      urchins. Big defensins from mollusks are mentioned together with amphioxus big
      defensin. The structures and activities of these defense proteins are discussed. 

PMID- 23968350
TI  - Cathelicidins: peptides with antimicrobial, immunomodulatory, anti-inflammatory,
      angiogenic, anticancer and procancer activities.
AB  - The family of peptides designated as cathelicidins was identified over a decade
      ago. Cathelicidins have since gained increasing recognition, both as endogenous
      antibiotics and as effector molecules of the innate immune system. The human
      cathelicidin LL-37 is widely expressed in human tissues and plays diverse
      biological roles. It contributes substantially to host defense and impacts
      multiple aspects of immunity. In view of the escalating importance of
      cathelicidins, the activities of LL-37 with an emphasis on antimicrobial,
      immunomodulatory, anti-inflammatory, angiogenic, anticancer and procancer effects
      are discussed in this review article. 

PMID- 23968351
TI  - Studies on anticancer activities of lactoferrin and lactoferricin.
AB  - This review mainly summarizes results of recent studies on the anticancer
      activity of the multifunctional protein lactoferrin (Lf) and its derived peptide
      lactoferricin (Lfcin). The basic information on Lf and Lfcin, such as their
      sources, structures, and biological properties which favor their antitumor
      activity is introduced. The major anticancer mechanisms of Lf and Lfcin including
      cell cycle arrest, apoptosis, anti-angiogenesis, antimetastasis, immune
      modulation and necrosis are discussed. Other information from in vivo studies
      employing a mouse model is also provided. In addition, the roles of talatoferrin
      and delta lactoferrin, as well as improvement in drug delivery will be covered. 

PMID- 23968352
TI  - Lectins in human cancer: both a devil and an angel?
AB  - Lectins are a group of proteins which could recognize different sugar structures
      and specifically initiate reversible binding with them. Lectins are universally
      expressed in different organisms and undertake important biological roles.
      Understanding of their inherent roles and mechanisms that they employ has
      inspired researches with new ideas and applications. For example, along with the
      revelation of their anti-insect function, plant lectins exhibit great potential
      in agriculture. In human beings, lectins shoulder great missions in cell
      communication, differentiation and vesicle trafficking etc., aberrant expression
      of lectins is always associated with diseases. Mannan-binding lectin deficiency
      leads to immune disorder and liver sinusoidal endothelial cell lectin is involved
      in colorectal carcinoma liver metastasis. In this review, we present two
      contradictory roles of lectins in human cancer: the promotive roles of homologous
      lectins and suppressive roles of heterologous lectins in cancer development.
      Hopefully, this review will facilitate a better understanding of tumorigenesis
      and provide references for cancer treatment. 

PMID- 23968353
TI  - Emerging roles for vasoactive peptides in diagnostic and therapeutic strategies
      against atherosclerotic cardiovascular diseases.
AB  - Coronary artery disease (CAD) arising from atherosclerosis remains the most
      common cause of death and morbidity worldwide, although its risk factors, such as
      hypertension, dyslipidemia, and diabetes, have been individually treated with
      increasingly improved outcomes. Therefore, it is important to develop diagnostic
      and therapeutic windows for CAD. Many classical vasoactive hormones, inflammatory
      cytokines, and oxidative products have been implicated as potential biomarkers.
      Our recent studies have shown that high levels of the pro-atherogenic vasoactive
      agents, serotonin and urotensin II, which are potent vasoconstrictors, can be
      used as biomarkers for CAD. In subsequent trials, we unraveled anti- and pro
      atherogenic roles for more recently identified peptides. Anti-atherogenic
      peptides include the adipocytokine adiponectin, the neuronal growth factor
      heregulin-beta1 (neuregulin-1 type I), the incretin hormone, glucagon-like
      peptide-1 (GLP-1), and a peptide recently identified by an in silico approach,
      salusin-alpha. Atherogenic roles have been demonstrated by cellular, animal, and
      clinical experiments, which indicate that human adiponectin, heregulin-beta1, GLP
      1, and salusin-alpha attenuate the development of atherosclerotic lesions by
      suppressing macrophage foam cell formation via down-regulation of acyl
      CoA:cholesterol acyltransferase-1. Circulating levels of these peptides in the
      blood are markedly decreased in CAD patients compared with those in non-CAD
      patients. Receiver operating characteristic curve analyses have shown that
      salusin-alpha is the most useful biomarker for detecting CAD among the four
      peptides examined. Therefore, salusin-alpha, alone or in various combinations
      with heregulin-beta1, adiponectin, and/or GLP-1, is a candidate biomarker for
      predicting CAD. Further, anti-atherogenic peptides could potentially serve as
      useful therapeutic targets for atherosclerotic cardiovascular diseases.

PMID- 23968354
TI  - Pharmacological potential of exercise and RAS vasoactive peptides for prevention
      of diseases.
AB  - The Renin-Angiotensin-System (RAS) molecular network has been widely studied,
      especially with attention to angiotensin II, the main effector peptide among RAS.
      The relation of Ang II to hypertension pathogenesis has led to research being
      extended to other molecules from the RAS, such as angiotensin III and IV,
      angiotensin (1-5), and angiotensin (1-9). Moreover, great pharmacologic advances
      have been made in hypertension treatment by inhibiting renin and angiotensin
      converting enzymes and blocking the bonding of angiotensin II to its receptor
      AT1. Thus, RAS molecular signaling and its effect on blood pressure as well as
      its relationship to renal function and cardiovascular disease are still being
      investigated. It is a great challenge to fully cover and understand all molecules
      from the RAS, especially those that interfere with or have vasoactive properties.
      Some of these targets respond to exercise, stimulating nitric oxide synthesis and
      endothelial vasodilation. The activation of these specific molecules via exercise
      is a systematic way of controlling high blood pressure without pharmacological
      treatment. Angiotensin (1-7) has been focused due to its vasodilation properties
      and its responses to exercise, improving vascular function. Thus, stimulation of
      the ACE2/Ang (1-7)/Mas axis has been gaining ground as a prospective clinical
      means to attenuate cardiovascular diseases such as hypertension by modulating RAS
      activity. This review focuses on the vasoactive peptides from the RAS, their
      responses to exercise and possible trends for pharmacological development. In
      several cases where exercise training is not achievable, cardiovascular drug
      therapy with vasodilator peptides may possibly be an option. 

PMID- 23968355
TI  - Combining "omics" strategies to analyze the biotechnological potential of complex
      microbial environments.
AB  - It is well established in the scientific literature that only a small fraction of
      microorganisms can be cultured by conventional microbiology methods. The ever
      cheaper and faster DNA sequencing methods, together with advances in
      bioinformatics, have improved our understanding of the structure and functional
      behavior of microbial communities in many complex environments. However, the
      metagenomics approach alone cannot elucidate the functionality of all
      microorganisms, because a vast number of potentially new genes have no homologs
      in public databases. Metatranscriptomics and metaproteomics are approaches based
      on different techniques and have recently emerged as promising techniques to
      describe microbial activities within a given environment at the molecular level.
      In this review, we will discuss current developments and applications of
      metagenomics, metatranscriptomics and metaproteomics, and their limitations in
      the study of microbial communities. The combined analysis of genes, mRNA and
      protein in complex microbial environments will be key to identify novel
      biological molecules for biotechnological purposes. 

PMID- 23968356
TI  - General one-pot template-free hydrothermal method to metal oxide hollow spheres
      and their photocatalytic activities and lithium storage properties.
AB  - A general and facile one-pot template-free hydrothermal strategy has been
      developed to synthesize various metal oxide (TiO2, SnO2 and alpha-Fe2O3) hollow
      spheres with unified morphologies. The formation of hollow structure involves a
      trifluoroacetic acid (TFA)-assisted Ostwald ripening process. Photocatalytic
      activities of the as-prepared TiO2 product are evaluated by the photodegradation
      of Rhodamine B (RhB), which the TiO2 hollow spheres obtained from 450  degrees C
      thermal treatment exhibit higher photocatalytic activity than Degussa P25. In
      addition, electrochemical measurements demonstrate that all of the as-prepared
      metal oxides hollow spheres have the potential applications in lithium-ion
      battery. We have a great expectation that this synthesis strategy can afford a
      new universal route for functional metal oxide hollow materials preparation
      without using template. 

PMID- 23968357
TI  - Public attitudes to organ donation among a sample of urban-dwelling South African
      adults: a 2012 study.
AB  - BACKGROUND: Published literature suggests that attitudes toward organ donation in
      South Africa are generally positive. However, there has been a decline in the
      actual number of transplants taking place annually, which is not consistent with
      expressed positive attitudes. OBJECTIVES: Assess the attitudes of a
      representative sample of the urban-dwelling South African population toward organ
      donation and how these might affect transplant numbers. METHODS: A structured
      questionnaire was utilized to measure attitudes among a study population of 1048
      adults in five major metropolitan areas of South Africa. Field work was
      undertaken by supervised field workers. Written informed consent was obtained
      from all participants. RESULTS: Eighty-nine percent (89%) of respondents had
      heard of organ donation, and 77% indicated that they would accept an organ
      transplant if necessary. Seventy percent (70%) of respondents specified they
      would be willing to donate their own organs after death, while 67% expressed
      willingness to donate a relative's organs after death. Participants were more
      positive about kidney donation than any other organ. CONCLUSION: Public attitudes
      toward organ donation among this population are generally positive.
      Recommendations include cultural and linguistic sensitivity in educational and
      advertising campaigns, as well as extensive research into other possible causes
      of organ shortage.

PMID- 23968358
TI  - Optical imaging of treatment-related tumor cell death using a heat shock protein
      90 alkylator.
AB  - The ability to assess in near-real time the tumor cell killing efficacy of
      chemotherapy regimens would improve patient treatment and survival. An
      ineffective regimen could be abandoned early in favor of a more effective
      treatment. We sought to noninvasively image treatment-related tumor cell death in
      mice using an optically labeled synthetic heat shock protein-90 (Hsp90)
      alkylator, 4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid (GSAO). The Hsp90
      chaperone is an important element in oncogene addiction and tumor cell survival,
      and its expression is enhanced by chemotherapy. These factors were predicted to
      favor the detection of tumor cell death using GSAO. GSAO specifically labeled
      apoptotic and necrotic tumor cells in culture and cells of comparable morphology
      in subcutaneous human pancreatic carcinoma tumors in mice. A near-infrared
      fluorescent conjugate of GSAO was used to noninvasively image cyclophosphamide
      induced tumor cell death in murine orthotopic human mammary tumors. The GSAO
      conjugate did not accumulate in healthy organs or tissues in the mouse, and
      unbound compound was excreted rapidly via the kidneys. There was a significant
      increase in the GSAO fluorescence signal in the treated tumors measured either in
      vivo or ex vivo, and the fluorescence signal colocalized with apoptotic cells in
      sectioned tumors. The favorable biodistribution of optically labeled GSAO, the
      nature of its tumor cell target, and its capacity to noninvasively detect tumor
      cell death should facilitate the application of this compound in studies of the
      efficacy of existing and new chemotherapeutics. 

PMID- 23968359
TI  - Cytomegalovirus (CMV) seroprevalence in Japanese blood donors and high detection
      frequency of CMV DNA in elderly donors.
AB  - BACKGROUND: The current prevalence of cytomegalovirus (CMV) in Japan and the risk
      of CMV transfusion transmission are unknown in the era of seronegative
      leukoreduced blood components. STUDY DESIGN AND METHODS: We measured CMV-specific
      immunoglobulin (Ig)M and IgG in 2400 samples of whole blood collected from 12
      groups of blood donors categorized by sex and age at 10-year intervals from their
      teens to their 60s. We also tested for CMV DNA using polymerase chain reaction in
      the cellular fractions of all samples. RESULTS: We found that 76.6% of blood
      donors were CMV seropositive. The seroprevalences among donors in their 20s and
      30s were 58.3 and 73.3%, respectively. We detected CMV DNA in the cellular
      fraction of 4.3% of samples from donors in their 60s and in 1.0% of samples from
      donors younger than 60 years. None of the 562 seronegative samples was DNA
      positive. Furthermore, 14% of DNA-positive samples also contained DNA in the
      plasma fraction, and two of five such samples were derived from donors in their
      60s. Leukoreduced plasma components derived from donations with CMV DNA in plasma
      samples also contained a relevant amount of CMV DNA. CONCLUSION: The
      seroprevalence of CMV among Japanese blood donors of child-bearing age has not
      changed over the past 15 years. Latent CMV becomes reactivated more frequently
      among elderly donors than among younger donors. A proportion of them have free
      CMV DNA in their plasma fraction, which could not be diminished by
      leukoreduction. The risk of transfusion-transmitted CMV infection in blood with
      plasma CMV DNA should be determined.

PMID- 23968361
TI  - Design and synthesis of tetrahydrophthalimide derivatives as inhibitors of HIV-1
      reverse transcriptase.
AB  - BACKGROUND: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are one of
      the key components in highly active anti-retroviral therapy because of their high
      specificity and less toxicity. NNRTIs inhibit reverse transcriptase enzyme by
      binding to the allosteric site, which is 10A away from the active site. Rapid
      emergence of resistance is the major problem with all anti-HIV agents. Hence,
      there is continuous need to develop novel anti-HIV agents active against both
      drug sensitive and resistance strains. RESULTS: All the 16 synthesized 2-(1,3
      dioxo-3a,4-dihydro-1H-isoindol-2(3H,7H,7aH)-yl)-N-(substitutedphenyl) acetamide
      4(a-p) analogs were characterized by Fourier transform infrared spectroscopy,
      proton nuclear magnetic resonance spectroscopy, mass spectroscopy, and elemental
      analysis. Lipinski rule of five parameters and molecular parameters like
      solubility, drug likeness, and drug score were derived for designed analogs using
      online servers like Molinspiration and Osiris property explorer. Synthesized
      compounds were evaluated for their HIV-1 reverse transcriptase inhibitor activity
      by HIV-1 RNA-dependent DNA polymerase activity assay at 2 and 20 MUM
      concentrations. CONCLUSIONS: Among the 16 synthesized compounds, 4a, 4b, 4f, 4g,
      4k, and 4l showed weak reverse transcriptase inhibitor activity at 20 MUM
      concentration. For the designed compounds, there was no correlation observed
      between molecular modeling and in vitro studies.

PMID- 23968360
TI  - Evaluation of cytotoxic, genotoxic and inflammatory responses of nanoparticles
      from photocopiers in three human cell lines.
AB  - BACKGROUND: Photocopiers emit nanoparticles with complex chemical composition.
      Short-term exposures to modest nanoparticle concentrations triggered upper airway
      inflammation and oxidative stress in healthy human volunteers in a recent study.
      To further understand the toxicological properties of copier-emitted
      nanoparticles, we studied in-vitro their ability to induce cytotoxicity, pro
      inflammatory cytokine release, DNA damage, and apoptosis in relevant human cell
      lines. METHODS: Three cell types were used: THP-1, primary human nasal- and small
      airway epithelial cells. Following collection in a large volume photocopy center,
      nanoparticles were extracted, dispersed and characterized in the cell culture
      medium. Cells were doped at 30, 100 and 300 MUg/mL administered doses for up to
      24 hrs. Estimated dose delivered to cells, was ~10% and 22% of the administered
      dose at 6 and 24 hrs, respectively. Gene expression analysis of key biomarkers
      was performed using real time quantitative PCR (RT-qPCR) in THP-1 cells at 5 MUg
      nanoparticles/mL for 6-hr exposure for confirmation purposes. RESULTS: Multiple
      cytokines, GM-CSF, IL-1beta, IL-6, IL-8, IFNgamma, MCP-1, TNF-alpha and VEGF,
      were significantly elevated in THP-1 cells in a dose-dependent manner. Gene
      expression analysis confirmed up-regulation of the TNF-alpha gene in THP-1 cells,
      consistent with cytokine findings. In both primary epithelial cells, cytokines IL
      8, VEGF, EGF, IL-1alpha, TNF-alpha, IL-6 and GM-CSF were significantly elevated.
      Apoptosis was induced in all cell lines in a dose-dependent manner, consistent
      with the significant up-regulation of key apoptosis-regulating genes P53 and
      Casp8 in THP-1 cells. No significant DNA damage was found at any concentration
      with the comet assay. Up-regulation of key DNA damage and repair genes, Ku70 and
      Rad51, were also observed in THP-1 cells, albeit not statistically significant.
      Significant up-regulation of the key gene HO1 for oxidative stress, implicates
      oxidative stress induced by nanoparticles. CONCLUSIONS: Copier-emitted
      nanoparticles induced the release of pro-inflammatory cytokines, apoptosis and
      modest cytotoxicity but no DNA damage in all three-human cell lines. Taken
      together with gene expression data in THP-1 cells, we conclude that these
      nanoparticles are directly responsible for inflammation observed in human
      volunteers. Further toxicological evaluations of these nanoparticles, including
      across different toner formulations, are warranted.

PMID- 23968362
TI  - Assistive technologies after stroke: self-management or fending for yourself? A
      focus group study.
AB  - BACKGROUND: Assistive Technologies, defined as "electrical or mechanical devices
      designed to help people recover movement" have demonstrated clinical benefits in
      upper-limb stroke rehabilitation. Stroke services are becoming community-based
      and more reliant on self-management approaches. Assistive technologies could
      become important tools within self-management, however, in practice, few people
      currently use assistive technologies. This study investigated patients', family
      caregivers and health professionals' experiences and perceptions of stroke upper
      limb rehabilitation and assistive technology use and identified the barriers and
      facilitators to their use in supporting stroke self-management. METHODS: A three
      day exhibition of assistive technologies was attended by 204 patients, family
      caregivers/friends and health professionals. Four focus groups were conducted
      with people purposively sampled from exhibition attendees. They included i)
      people with stroke who had used assistive technologies (n = 5), ii) people with
      stroke who had not used assistive technologies (n = 6), iii) family caregivers (n
      = 5) and iv) health professionals (n = 6). The audio-taped focus groups were
      facilitated by a moderator and observer. All participants were asked to discuss
      experiences, strengths, weaknesses, barriers and facilitators to using assistive
      technologies. Following transcription, data were analysed using thematic
      analysis. RESULTS: All respondents thought assistive technologies had the
      potential to support self-management but that this opportunity was currently
      unrealised. All respondents considered assistive technologies could provide a
      home-based solution to the need for high intensity upper-limb rehabilitation. All
      stakeholders also reported significant barriers to assistive technology use,
      related to i) device design ii) access to assistive technology information and
      iii) access to assistive technology provision. The lack of and need for a
      coordinated system for assistive technology provision was apparent. A circular
      limitation of lack of evidence in clinical settings, lack of funded provision,
      lack of health professional knowledge about assistive technologies and confidence
      in prescribing them leading to lack of assistive technology service provision
      meant that often patients either received no assistive technologies or they
      and/or their family caregivers liaised directly with manufacturers without any
      independent expert advice. CONCLUSIONS: Considerable systemic barriers to
      realising the potential of assistive technologies in upper-limb stroke
      rehabilitation were reported. Attention needs to be paid to increasing evidence
      of assistive technology effectiveness and develop clinical service provision.
      Device manufacturers, researchers, health professionals, service funders and
      people with stroke and family caregivers need to work creatively and
      collaboratively to develop new funding models, improve device design and increase
      knowledge and training in assistive technology use.

PMID- 23968363
TI  - Fabrication of luminescent monolayered tungsten dichalcogenides quantum dots with
      giant spin-valley coupling.
AB  - A high yield (>36 wt %) method has been developed of preparing monolayered
      tungsten dichalcogenide (WS2) quantum dots (QDs) with lateral size ~8-15 nm from
      multilayered WS2 flakes. The monolayered WS2 QDs are, like monolayered WS2
      sheets, direct semiconductors despite the flake precursors being an indirect
      semiconductor. However, the QDs have a significantly larger direct transition
      energy (3.16 eV) compared to the sheets (2.1 eV) and enhanced photoluminescence
      (PL; quantum yield ~4%) in the blue-green spectral region at room temperature.
      UV/vis measurements reveal a giant spin-valley coupling of the monolayered WS2
      QDs at around 570 meV, which is larger than that of monolayered WS2 sheets (~400
      meV). This spin-valley coupling was further confirmed by PL as direct transitions
      from the conduction band minimum to split valence band energy levels, leading to
      multiple luminescence peaks centered at around 369 (3.36 eV) and 461 nm (2.69 eV,
      also contributed by a new defect level). The discovery of giant spin-valley
      coupling and the strong luminescence of the monolayered WS2 QDs make them
      potentially of interests for the applications in semiconductor-based spintronics,
      conceptual valley-based electronics, quantum information technology and
      optoelectronic devices. However, we also demonstrate that the fabricated
      monolayered WS2 QDs can be a nontoxic fluorescent label for high contrast
      bioimaging application. 

PMID- 23968364
TI  - Mediating toxic emotions in the workplace--the impact of abusive supervision.
AB  - AIM: This study explores whether abusive supervision can effectively predict
      employees' counterproductive work behaviour (CWB) and organisational citizenship
      behaviour (OCB) and the role of toxic emotions at work as a potential mediator of
      these relationships in nursing settings. BACKGROUND: Workplace bullying is
      widespread in nursing. Despite the growing literature on abusive supervision and
      employees' counterproductive work behaviour and organisational citizenship
      behaviour, few studies have examined the relationships between abusive
      supervision and these work behaviours from the viewpoint of the victimed
      employee's emotion process. METHODS: This study adopted a two-stage survey of 212
      nurses, all of whom were employed by hospitals in Taiwan. Hypotheses were tested
      through the use of hierarchical multiple regression. RESULTS: The results showed
      that abusive supervision was positively associated with toxic emotions. Moreover,
      toxic emotions could effectively predict nurses' counterproductive work behaviour
      and organisational citizenship behaviour. Finally, it was found that toxic
      emotions partially mediated the negative effects of abusive supervision on both
      work behaviours. CONCLUSION: Toxic emotions at work are a critical mediating
      variable between abusive supervision and both counterproductive work behaviour
      and organisational citizenship behaviour. Hospital administrators can implement
      policies designed to manage events effectively that can spark toxic emotions in
      their employees. IMPLICATIONS FOR NURSING MANAGEMENT: Work empowerment may be an
      effective way to reduce counterproductive work behaviour and to enhance
      organisational citizenship behaviour among nurses when supervisors do not promote
      a healthy work environment for them.

PMID- 23968365
TI  - Neonatal disorders of germinal matrix.
AB  - The germinal matrix (GM) is a richly vascularized, transient layer near the
      ventricles. It produces neurons and glial cells, and is present in the foetal
      brain between 8 and 36 weeks of gestation. At 25 weeks, it reaches its maximum
      volume and subsequently withers. The GM is vulnerable to haemorrhage in preterm
      infants. This selective vulnerability is explained by limited astrocyte end-feet
      coverage of microvessels, reduced expression of fibronectin and immature tight
      junctions. Focal lesions in the neonatal period include haemorrhage, germinolysis
      and stroke. Such lesions in transient layers interrupt normal brain maturation
      and induce neurodevelopmental sequelae. 

PMID- 23968366
TI  - Which patient and treatment factors are related to successful cardiovascular risk
      score reduction in general practice? Results from a randomized controlled trial.
AB  - BACKGROUND: Cardiovascular disease is a leading cause of death. It is important
      to identify patient and treatment factors that are related to successful
      cardiovascular risk reduction in general practice. This study investigates which
      patient and treatment factors are related to changes in cardiovascular risk
      estimation, expressed as the Systematic Coronary Risk Evaluation (SCORE) 10 year
      risk of cardiovascular mortality. METHODS: 179 general practice patients with
      mild-moderately elevated cardiovascular risk followed a one-year programme which
      included structured lifestyle and medication treatment by practice nurses, with
      or without additional self-monitoring. From the patient and treatment data
      collected as part of the "Self-monitoring and Prevention of RIsk factors by Nurse
      practitioners in the region of Groningen" randomized controlled trial (SPRING
      RCT), the contribution of patient and treatment factors to the change in SCORE
      was analysed with univariate and multivariate analyses. RESULTS: In multivariate
      analyses with multiple patient and treatment factors, only SCORE at baseline, and
      addition of or dose change in lipid lowering or antihypertensive medications over
      the course of the study were significantly related to change in SCORE.
      CONCLUSIONS: Our analyses support the targeting of treatment at individuals with
      a high SCORE at presentation. Lipid lowering medication was added or changed in
      only 12% of participants, but nevertheless was significantly related to
      DeltaSCORE in this study population. Due to the effect of medication in this
      practice-based project, the possible additional effect of the home monitoring
      devices, especially for individuals with no indication for medication, may have
      been overshadowed. TRIAL REGISTRATION: trialregister.nl NTR2188.

PMID- 23968367
TI  - Psychotherapeutic interventions in individuals at risk of developing bipolar
      disorder: a systematic review.
AB  - AIM: Accumulating data show that patients with bipolar disorder (BD) experience
      substantial symptomatology months or years before full manifestation. Based on
      the need for early preventive interventions in BD as well as data suggesting
      effectiveness of psychotherapeutic interventions for BD, we aimed to review the
      evidence for psychotherapeutic treatments in help-seeking individuals considered
      at risk for BD (At-Risk-BD). METHODS: Searching PubMed and PsycINFO, clinical
      trial registries and recently published systematic reviews, a systematic review
      was performed of psychoeducational and psychotherapeutic intervention studies in
      At-Risk-BD individuals. RESULTS: Only three completed studies were identified,
      two of which were randomized trials (n = 77) and one was an open pilot study (n =
      13). Two ongoing studies (projected n = 150 and n = 100, respectively) were found
      in trial registries. The available evidence suggests potential effectiveness of
      multi-family psychoeducational psychotherapy and family-focussed therapy for
      symptom reduction and prevention of BD conversion. CONCLUSIONS: Psychotherapeutic
      treatments are a reasonable starting point for At-Risk-BD subjects when symptom
      severity, distress and impairment are sufficiently significant to initiate
      treatment. Ongoing studies will further clarify the effectiveness and timing of
      psychotherapeutic interventions for At-Risk-BD individuals and whether or not
      they should be given alone or in conjunction with other treatments. Large multi
      site studies with standardized procedures/manuals are needed to advance the
      field.

PMID- 23968368
TI  - Microcystic adnexal carcinoma: successful management of a large scalp lesion.
AB  - Microcystic adnexal carcinoma (MAC) is a rare, malignant cutaneous neoplasm. It
      is important for us to become more aware of it, as it is often misdiagnosed,
      either clinically or histopathologically. We report a case of an extensive scalp
      lesion that was successfully treated using a combination of resection and
      adjuvant radiotherapy.

PMID- 23968369
TI  - One-stage correction of blepharophimosis-ptosis-epicanthus inversus syndrome
      using a frontalis muscle transfer technique.
AB  - Blepharophimosis-ptosis-epicanthus inversus (BPES) is a rare genetic disease
      involving a complex eyelid malformation. The surgical treatment approach for BPES
      is highly complex and a subject of controversy. This study reports the results of
      a one-stage frontalis muscle transfer technique to correct BPES. This
      retrospective, interventional study included 21 patients with BPES who had been
      followed-up for a minimum of 1 year. The one-stage intervention was a combination
      of three surgical techniques: Mustarde medial canthoplasty, Fox lateral
      canthoplasty, and the frontalis muscle transfer technique. Preoperative and
      postoperative measurements of the horizontal lid fissure length (HLFL), vertical
      lid fissure width (VLFW), inner intercanthal distance (IICD), and the IICD/HLFL
      ratio were analyzed by Wilcoxon's signed rank test. The mean preoperative
      measurements were 4.73 +/- 0.32 mm for VLFW, 19.98 +/- 3.74 mm for HLFL, 40.85 +/
      4.46 mm for IICD, and 2.11 +/- 0.45 mm for the IICD/HLFL ratio. The mean
      postoperative measurements were 7.86 +/- 0.41 mm for VLFW, 24.47 +/- 3.35 mm for
      HLFL, 32.52 +/- 4.16 mm for IICD, and 1.35 +/- 0.22 mm for the IICD/HLFL ratio (p
      < 0.0001 for all preoperative vs postoperative values). Postoperative
      complications included eyelid fold deformities, lagophthalmos, and conspicuous
      scars. Most of these complications gradually resolved. One-stage correction of
      BPES is safe and efficient with the surgical techniques described.

PMID- 23968371
TI  - A useful skin biopsy.

PMID- 23968372
TI  - Pressure-induced amorphization in single-crystal Ta2O5 nanowires: a kinetic
      mechanism and improved electrical conductivity.
AB  - Pressure-induced amorphization (PIA) in single-crystal Ta2O5 nanowires is
      observed at 19 GPa, and the obtained amorphous Ta2O5 nanowires show significant
      improvement in electrical conductivity. The phase transition process is unveiled
      by monitoring structural evolution with in situ synchrotron X-ray diffraction,
      pair distribution function, Raman spectroscopy, and transmission electron
      microscopy. The first principles calculations reveal the phonon modes softening
      during compression at particular bonds, and the analysis on the electron
      localization function also shows bond strength weakening at the same positions.
      On the basis of the experimental and theoretical results, a kinetic PIA mechanism
      is proposed and demonstrated systematically that amorphization is initiated by
      the disruption of connectivity between polyhedra (TaO6 octahedra or TaO7
      bipyramids) at the particular weak-bonding positions along the a axis in the unit
      cell. The one-dimensional morphology is well-preserved for the pressure-induced
      amorphous Ta2O5, and the electrical conductivity is improved by an order of
      magnitude compared to traditional amorphous forms. Such pressure-induced
      amorphous nanomaterials with unique properties surpassing those in either
      crystalline or conventional amorphous phases hold great promise for numerous
      applications in the future. 

PMID- 23968373
TI  - Label-free determination of the cell cycle phase in human embryonic stem cells by
      Raman microspectroscopy.
AB  - The cell cycle is a series of integrated and coordinated physiological events
      that results in cell growth and replication. Besides observing the event of cell
      division it is not feasible to determine the cell cycle phase without fatal
      and/or perturbing invasive procedures such as cell staining, fixing, and/or
      dissociation. Raman microspectroscopy (RMS) is a chemical imaging technique that
      exploits molecular vibrations as a contrast mechanism; it can be applied to
      single living cells noninvasively to allow unperturbed analysis over time. We
      used RMS to determine the cell cycle phase based on integrating the composite 783
      cm(-1) nucleic acid band intensities across individual cell nuclei. After
      correcting for RNA contributions using the RNA 811 cm(-1) band, the measured
      intensities essentially reflected DNA content. When quantifying Raman images from
      single cells in a population of methanol-fixed human embryonic stem cells, the
      histogram of corrected 783 cm(-1) band intensities exhibited a profile analogous
      to that obtained using flow-cytometry with nuclear stains. The two population
      peaks in the histogram occur at Raman intensities corresponding to a 1-fold and 2
      fold diploid DNA complement per cell, consistent with a distribution of cells
      with a population peak due to cells at the end of G1 phase (1-fold) and a peak
      due to cells entering M phase (2-fold). When treated with EdU to label the
      replicating DNA and block cell division, cells with higher EdU-related
      fluorescence generally had higher integrated Raman intensities. This provides
      proof-of-principle of an analytical method for label-free RMS determination in
      situ of cell cycle phase in adherent monolayers or even single adherent cells. 

PMID- 23968374
TI  - Graphene oxide-based fluorescent "on/off" switch for visual bioassay using
      "molecular beacon"-hosted Hoechst dyes.
AB  - In this study, the fluorescence of Hoechst dyes is significantly lit up by
      addition of our designed MB probe, forming a complex of "molecular beacon"-hosted
      Hoechst dyes (HMB). Combined with this property, a novel graphene oxide (GO)
      based fluorescent "on/off" switch was developed to visually follow bioassay
      utilizing HMB as signal indicators and GO as an excellent energy acceptor to
      efficiently quench the fluorescence of HMB in a label-easy format. We have
      demonstrated its application for label-easy fluorescence "turn on" detection of
      sequence-specific DNA and "turn off" detection of exonuclease with sensitivity
      and selectivity in a single step in homogeneous solution. Compared to traditional
      molecular beacons, the proposed design is cost-effective and simple to prepare
      without fluorescence labeling or chemical modification. 

PMID- 23968376
TI  - Across the structural re-entrant transition in BaFe2(PO4)2: influence of the two
      dimensional ferromagnetism.
AB  - BaFe2(PO4)2 was recently prepared by hydrothermal synthesis and identified as the
      first two-dimensional (2D) Ising ferromagnetic oxide, in which honeycomb layers
      made up of edge-sharing FeO6 octahedra containing high-spin Fe(2+) ions (S = 2)
      are isolated by PO4 groups and Ba(2+) cations. BaFe2(PO4)2 has a trigonal R-3
      structure at room temperature but adopts a triclinic P-1 structure below 140 K
      due to the Jahn-Teller (JT) instability arising from the (t2g)(4)(eg)(2)
      configuration. The triclinic crystal structure was refined to find significantly
      distorted Fe(2+)O6 octahedra in the honeycomb layers while the distortion
      amplitude QJT was estimated to 0.019 A. The JT stabilization energy is estimated
      to be ~7 meV per formula unit by DFT calculations. Below ~70 K, very close to the
      ferromagnetic transition temperature Tc = 65.5 K, the structure of BaFe2(PO4)2
      returns to a trigonal R-3 structure in the presence of significant ferromagnetic
      domains. This rare re-entrant structural transition is accompanied by a
      discontinuous change in the quadrupolar splitting of Fe(2+), as determined by
      Mossbauer spectroscopy. EPR measurements show the presence of magnetic domains
      well above Tc , as expected for a ferromagnetic 2D Ising system, and support that
      the magnetism of BaFe2(PO4)2 is uniaxial (g? = 0). 

PMID- 23968375
TI  - Resveratrol-loaded nanoparticles based on poly(epsilon-caprolactone) and poly(D,L
      lactic-co-glycolic acid)-poly(ethylene glycol) blend for prostate cancer
      treatment.
AB  - Nanoencapsulation of antiproliferative and chemopreventive phytoalexin trans
      resveratrol (RSV) is likely to provide protection against degradation,
      enhancement of bioavailability, improvement in intracellular penetration and
      control delivery. In this study, polymeric nanoparticles (NPs) encapsulating RSV
      (nano-RSV) as novel prototypes for prostate cancer (PCa) treatment were designed,
      characterized and evaluated using human PCa cells. Nanosystems, composed of a
      biocompatible blend of poly(epsilon-caprolactone) (PCL) and poly(d,l-lactic-co
      glycolic acid)-poly(ethylene glycol) conjugate (PLGA-PEG-COOH), were prepared by
      a nanoprecipitation method, and characterized in terms of morphology, particle
      size and zeta potential, encapsulation efficiency, thermal analyses, and in vitro
      release studies. Cellular uptake of NPs was then evaluated in PCa cell lines DU
      145, PC-3, and LNCaP using confocal fluorescence microscopy, and
      antiproliferative efficacy was assessed using MTT assay. With encapsulation
      efficiencies ranging from 74% to 98%, RSV was successfully loaded in PCL:PLGA-PEG
      COOH NPs, which showed an average diameter of 150 nm. NPs were able to control
      the RSV release at pH 6.5 and 7.4, mimicking the acidic tumoral microenvironment
      and physiological conditions, respectively, with only 55% of RSV released within
      7 h. In gastrointestinal simulated fluids, NPs released about 55% of RSV in the
      first 2 h in acidic medium, and their total RSV content within the subsequent 5 h
      at pH 7.4. Confocal fluorescence microscopy observations revealed that NPs were
      efficiently taken up by PCa cell lines. Furthermore, nano-RSV significantly
      improved the cytotoxicity compared to that of free RSV toward all three cell
      lines, at all tested concentrations (from 10 MUM to 40 MUM), proving a consistent
      sensitivity toward both the androgen-independent DU-145 and hormone-sensitive
      LNCaP cells. Our findings support the potential use of developed nanoprototypes
      for the controlled delivery of bioactive RSV for PCa
      chemoprevention/chemotherapy. 

PMID- 23968378
TI  - Emerging sodium/glucose co-transporter 2 inhibitors for type 2 diabetes.
AB  - INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a public health challenge
      globally. Numerous treatments are available which can improve insulin sensitivity
      or stimulate its secretion including biguanides, sulphonylureas and glitazones,
      as well as insulin, GLP-1 agonists and DPP-IV inhibitors. These are usually
      unable to halt progression with high resulting morbidity and mortality. New
      therapies are, therefore, being developed; inhibition of glucose reabsorption
      from the renal filtrate has been proposed as a novel therapeutic target, and
      sodium/glucose co-transporter 2 (SGLT2) inhibitors have been developed
      accordingly. AREAS COVERED: This review summarises the challenge that T2DM poses
      and describes established therapies. The market for these therapies and likely
      changes are examined, as well as the scientific rationale behind the development
      of SGLT2 inhibitors. SGLT2 inhibitors in clinical trials worldwide are reviewed
      and issues affecting their development are discussed. EXPERT OPINION: SGLT2
      inhibitors offer a novel therapeutic approach to the management of T2DM;
      advantages over other agents include weight loss and blood pressure lowering with
      a low intrinsic risk of hypoglycaemia. The main adverse effects likely to be seen
      in clinical practice are a very small increase in risk of urinary tract
      infections, and a modest risk of developing genital fungal infections - which
      appear more common in the first few months of treatment. Meta-analyses suggest no
      increased risk of cardiovascular disease, but longer duration outcome studies are
      essential to prove long-term safety and efficacy.

PMID- 23968377
TI  - Hyaluronic acid fragments enhance the inflammatory and catabolic response in
      human intervertebral disc cells through modulation of toll-like receptor 2
      signalling pathways.
AB  - INTRODUCTION: Intervertebral disc (IVD) degeneration is characterized by
      extracellular matrix breakdown and is considered to be a primary cause of
      discogenic back pain. Although increases in pro-inflammatory cytokine levels
      within degenerating discs are associated with discogenic back pain, the
      mechanisms leading to their overproduction have not yet been elucidated. As
      fragmentation of matrix components occurs during IVD degeneration, we assessed
      the potential involvement of hyaluronic acid fragments (fHAs) in the induction of
      inflammatory and catabolic mediators. METHODS: Human IVD cells isolated from
      patient biopsies were stimulated with fHAs (6 to 12 disaccharides) and their
      effect on cytokine and matrix degrading enzyme production was assessed using
      quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked
      immunosorbent assay (ELISA). The involvement of specific cell surface receptors
      and signal transduction pathways in mediating the effects of fHAs was tested
      using small interfering RNA (siRNA) approaches and kinase inhibition assays.
      RESULTS: Treatment of IVD cells with fHAs significantly increased mRNA expression
      levels of interleukin (IL)-1beta, IL-6, IL-8, cyclooxygenase (COX)-2, matrix
      metalloproteinase (MMP)-1 and -13. The stimulatory effects of fHAs on IL-6
      protein production were significantly impaired when added to IVD cells in
      combination with either Toll-like receptor (TLR)-2 siRNA or a TLR2 neutralizing
      antibody. Furthermore, the ability of fHAs to enhance IL-6 and MMP-3 protein
      production was found to be dependent on the mitogen-activated protein (MAP)
      kinase signaling pathway. CONCLUSIONS: These findings suggest that fHAs may have
      the potential to mediate IVD degeneration and discogenic back pain through
      activation of the TLR2 signaling pathway in resident IVD cells.

PMID- 23968379
TI  - Emerging drugs for polycythemia vera.
AB  - INTRODUCTION: Polycythemia vera (PV) patients suffer from disease-related
      constitutional symptoms, cardiovascular complications and risk of transformation
      into myelofibrosis and acute leukemia. AREAS COVERED: Clinical and molecular
      aspects and current therapies will be described to provide clinical and molecular
      background to understand the natural history and treatment strategies in PV.
      Pertinent ongoing research questions, challenges arising out of the specific
      disease course and biology of PV as well as challenges and opportunities for new
      agents in PV are addressed. A focus is placed on pegylated interferon-alpha
      formulations (PEG-INFa2a) and JAK2 inhibitors. Newest data on symptom burden and
      incidence and prevalence of PV and MPNs are highlighted in the context of
      development of PV therapies. EXPERT OPINION: Therapeutic goals in PV are to
      prevent vascular events, reduce symptoms and for future therapies delay/prevent
      disease progression. Currently available treatments such as phlebotomy,
      antiplatelet therapy, managing risk factors and cytoreductive therapies such as
      hydroxyurea (HU) and PEG-INFa2a are effective. JAK2 inhibitors recently have
      shown promising activity in reducing PV symptoms and spleen size and improving
      blood counts. Yet the influence of long-term outcome and delaying disease
      progression is unknown. Thus, there still remains an unmet medical need for
      improved therapy and symptom management in PV.

PMID- 23968381
TI  - Many ways lead to Rome: a glance at the multiple immunological pathways
      underlying atopic dermatitis.

PMID- 23968382
TI  - Utilizing metabolomics to distinguish asthma phenotypes: strategies and clinical
      implications.

PMID- 23968383
TI  - Risk of angioedema following invasive or surgical procedures in HAE type I and II
      -the natural history.
AB  - BACKGROUND: Hereditary angioedema (HAE), caused by deficiency in C1-inhibitor (C1
      INH), leads to unpredictable edema of subcutaneous tissues with potentially fatal
      complications. As surgery can be a trigger for edema episodes, current guidelines
      recommend preoperative prophylaxis with C1-INH or attenuated androgens in
      patients with HAE undergoing surgery. However, the risk of an HAE attack in
      patients without prophylaxis has not been quantified. OBJECTIVES: This analysis
      examined rates of perioperative edema in patients with HAE not receiving
      prophylaxis. METHODS: This was a retrospective analysis of records of randomly
      selected patients with HAE type I or II treated at the Frankfurt Comprehensive
      Care Centre. These were examined for information about surgical procedures and
      the presence of perioperative angioedema. RESULTS: A total of 331 patients were
      included; 247 underwent 700 invasive procedures. Of these procedures, 335 were
      conducted in 144 patients who had not received prophylaxis at the time of
      surgery. Categories representing significant numbers of procedures were abdominal
      (n = 113), ENT (n = 71), and gynecological (n = 58) procedures. The rate of
      documented angioedema without prophylaxis across all procedures was 5.7%; in
      24.8% of procedures, the presence of perioperative angioedema could not be
      excluded, leading to a maximum potential risk of 30.5%. Predictors of
      perioperative angioedema could not be identified. CONCLUSION: The risk of
      perioperative angioedema in patients with HAE type I or II without prophylaxis
      undergoing surgical procedures ranged from 5.7% to 30.5% (CI 3.5-35.7%). The
      unpredictability of HAE episodes supports current international treatment
      recommendations to consider short-term prophylaxis for all HAE patients
      undergoing surgery.

PMID- 23968384
TI  - Vitamin D in early life: good or bad for food allergies?

PMID- 23968385
TI  - Ghana's National Health Insurance Scheme: a national level investigation of
      members' perceptions of service provision.
AB  - BACKGROUND: Ghana's National Health Insurance Scheme (NHIS), established into law
      in 2003 and implemented in 2005 as a 'pro-poor' method of health financing, has
      made great progress in enrolling members of the general population. While many
      studies have focused on predictors of enrolment this study offers a novel
      analysis of NHIS members' perceptions of service provision at the national level.
      METHODS: Using data from the 2008 Ghana Demographic Health Survey we analyzed the
      perceptions of service provision as indicated by members enrolled in the NHIS at
      the time of the survey (n = 3468; m = 1422; f = 2046). Ordinal Logistic
      Regression was applied to examine the relationship between perceptions of service
      provision and theoretically relevant socioeconomic and demographic variables.
      RESULTS: Results demonstrate that wealth, gender and ethnicity all play a role in
      influencing members' perceptions of NHIS service provision, distinctive from its
      influence on enrolment. Notably, although wealth predicted enrolment in other
      studies, our study found that compared to the poorest men and uneducated women,
      wealthy men and educated women were less likely to perceive their service
      provision as better/same (more likely to report it was worse). Wealth was not an
      important factor for women, suggesting that household gender dynamics supersede
      household wealth status in influencing perceptions. As well, when compared to
      Akan women, women from all other ethnic groups were about half as likely to
      perceive the service provision to be better/same. CONCLUSIONS: Findings of this
      study suggest there is an important difference between originally enrolling in
      the NHIS because one believes it is potentially beneficial, and using the NHIS
      and perceiving it to be of benefit. We conclude that understanding the nature of
      this relationship is essential for Ghana's NHIS to ensure its longevity and meet
      its pro-poor mandate. As national health insurance systems are a relatively new
      phenomenon in sub-Saharan Africa little is known about their long term viability;
      understanding user perceptions of service provision is an important piece of that
      puzzle.

PMID- 23968386
TI  - Configuration of wobble base pairs having pyrimidines as anticodon wobble bases:
      significance for codon degeneracy.
AB  - Degeneracy of the genetic code was attributed by Crick to imprecise hydrogen
      bonded base-pairing at the wobble position during codon-anticodon pairing. The
      Crick wobble rules define but do not explain the RNA base pair combinations
      allowed at this position. We select six pyrimidine bases functioning as anticodon
      wobble bases (AWBs) to study their H-bonded pairing properties with the four
      major RNA bases using density functional theory at the B3LYP/6-31G(d,p) level.
      This is done to assess the extent to which the configuration of a solitary RNA
      wobble base pair may in itself determine specificity and degeneracy of the
      genetic code by allowing or disallowing the given base pair during codon
      anticodon pairing. Calculated values of select configuration markers for the base
      pairs screen well between allowed and disallowed base pairs for most cases
      examined here, where the base pair width emerges as an important factor. A few
      allowed wobble pairs invoke the involvement of RNA nucleoside conformation, as
      well as involvement of the exocyclic substituent in H-bonding. This study,
      however, cannot explain the disallowed status of the Ura?Gua wobble pair on the
      basis of configuration alone. Explanation of the allowed status of the V?Ura pair
      requires further study on the mediatory role of water molecules. Apart from these
      two cases, these computational results are sufficient, on the basis of base pair
      configuration alone, to account for the specificity and degeneracy of the genetic
      code for all known cases of codon-anticodon pairing which involve the pyrimidine
      AWBs studied here. 

PMID- 23968388
TI  - Brain susceptibility to oxidative stress in the perinatal period.
AB  - Oxidative stress (OS) occurs at birth in all newborns as a consequence of the
      hyperoxic challenge due to the transition from the hypoxic intrauterine
      environment to extrauterine life. Free radical (FRs) sources such as
      inflammation, hyperoxia, hypoxia, ischaemia-reperfusion, neutrophil and
      macrophage activation, glutamate and free iron release, all increases the OS
      during the perinatal period. Newborns, and particularly preterm infants, have
      reduced antioxidant defences and are not able to counteract the harmful effects
      of FRs. Energy metabolism is central to life because cells cannot exist without
      an adequate supply of ATP. Due to its growth, the mammalian brain can be
      considered as a steady-state system in which ATP production matches ATP
      utilisation. The developing brain is particularly sensitive to any disturbances
      in energy generation, and even a short-term interruption can lead to long-lasting
      and irreversible damage. Whenever energy failure develops, brain damage can
      occur. Accumulating evidence indicates that OS is implicated in the pathogenesis
      of many neurological diseases, such as intraventricular haemorrhage, hypoxic
      ischaemic encephalopathy and epilepsy. 

PMID- 23968387
TI  - Ambient fine particulate matter and ozone exposures induce inflammation in
      epicardial and perirenal adipose tissues in rats fed a high fructose diet.
AB  - BACKGROUND: Inflammation and oxidative stress play critical roles in the
      pathogenesis of inhaled air pollutant-mediated metabolic disease. Inflammation in
      the adipose tissues niches are widely believed to exert important effects on
      organ dysfunction. Recent data from both human and animal models suggest a role
      for inflammation and oxidative stress in epicardial adipose tissue (EAT) as a
      risk factor for the development of cardiovascular disease. We hypothesized that
      inhalational exposure to concentrated ambient fine particulates (CAPs) and ozone
      (O3) exaggerates inflammation and oxidative stress in EAT and perirenal adipose
      tissue (PAT). METHODS: Eight- week-old Male Sprague-Dawley rats were fed a normal
      diet (ND) or high fructose diet (HFr) for 8 weeks, and then exposed to ambient
      AIR, CAPs at a mean of 356 MUg/m3, O3 at 0.485 ppm, or CAPs (441 MUg/m3) + O3
      (0.497 ppm) in Dearborn, MI, 8 hours/day, 5 days/week, for 9 days over 2 weeks.
      RESULTS: EAT and PAT showed whitish color in gross, and less mitochondria, higher
      mRNA expression of white adipose specific and lower brown adipose specific genes
      than in brown adipose tissues. Exposure to CAPs and O3 resulted in the increase
      of macrophage infiltration in both EAT and PAT of HFr groups. Proinflammatory
      genes of Tnf-alpha, Mcp-1 and leptin were significantly upregulated while IL-10
      and adiponectin, known as antiinflammatory genes, were reduced after the
      exposures. CAPs and O3 exposures also induced an increase in inducible nitric
      oxide synthase (iNOS) protein expression, and decrease in mitochondrial area in
      EAT and PAT. We also found significant increases in macrophages of HFr-O3 rats.
      The synergetic interaction of HFr and dirty air exposure on the inflammation was
      found in most of the experiments. Surprisingly, exposure to CAPs or O3 induced
      more significant inflammation and oxidative stress than co-exposure of CAPs and
      O3 in EAT and PAT. CONCLUSION: EAT and PAT are both white adipose tissues. Short
      term exposure to CAPs and O3, especially with high fructose diet, induced
      inflammation and oxidative stress in EAT and PAT in rats. These findings may
      provide a link between air-pollution exposure and accelerated susceptibility to
      cardiovascular disease and metabolic complications.

PMID- 23968389
TI  - What determines the self-rated health of older individuals with stroke compared
      to other older individuals? A cross-sectional analysis of the Medical Research
      Council Cognitive Function and Aging Study.
AB  - BACKGROUND: Poor self-rated health has been associated with poorer objective
      health outcomes across a range of conditions including stroke. Identification of
      factors associated with poor self-rated health in stroke survivors has received
      little attention compared to that in other older individuals. This study
      identifies determinants of self-rated health in older individuals with or without
      a history of stroke participating in the population-representative MRC Cognitive
      Function and Aging Study (MRC CFAS). METHODS: The MRC CFAS is a multicentred
      longitudinal survey of a population representative sample of people in their 65th
      year and older at baseline. Baseline interview included questions about
      functional disability, psychiatric history, independent living status, social
      interactions, and cognitive function. Multiple logistic regression was used to
      determine associations between demographic, physical, cognitive, psychological
      and social factors with poor self-rated health among those with and without
      stroke. RESULTS: After excluding those with impaired cognitive function, 776
      individuals out of 11,957 reported a stroke. Factors associated with self-rated
      health were similar between those with or without a stroke in older individuals.
      Poorer self-rated health in those who had suffered a stroke was associated
      predominantly with the presence of comorbidity with diabetes (OR 3.5; 95% CI 1.5
      8.1) and not "getting out and about" (OR 2.6; 95% CI 1.7-4.1) even after
      adjustment for disability levels and for depression. In those without a stroke
      the most important determinants were disability (OR 3.9; 95% CI 3.2-4.8) and not
      "getting out and about" (OR 2.9; 95% CI 2.5-3.3). The presence of disability was
      less strongly associated with poor self-rated health in those with a history of
      stroke than those without due to a substantially higher reporting of poor self
      rated health in the non-disabled stroke group than the non-disabled stroke-free
      group, while those with disabilities reported poor self-rated health irrespective
      of stroke status. CONCLUSIONS: Self-rated health is determined by a range of
      psychological and social factors in addition to disability in older patients with
      stroke. Addressing social integration and mobility out of the home is an
      important element of rehabilitation for older people with stroke as well as those
      without.

PMID- 23968390
TI  - Metabolic changes in first-episode early-onset schizophrenia with second
      generation antipsychotics.
AB  - AIM: Individuals with a diagnosis of schizophrenia have a reduced life expectancy
      compared with the general population and cardiovascular disease is the major
      contributor to this early mortality. The use of second-generation antipsychotic
      (SGA) medications is associated with significant weight gain and metabolic side
      effects; however, there is limited knowledge in certain diagnostic groups,
      specifically early-onset schizophrenia (EOS). This study aimed to investigate the
      metabolic side effects of SGAs, specifically olanzapine, risperidone and
      quetiapine, in a cohort of drug-naive children and adolescents with first-episode
      EOS. METHOD: Body mass index (BMI), serum cholesterol and triglycerides were
      measured at baseline and a median of 7 months of follow up in drug-naive children
      and adolescents with EOS. RESULTS: A total of 49 children and adolescents
      received a diagnosis of first-episode EOS and we had complete follow-up data for
      74% (N = 36). A significant increase in BMI, serum triglycerides and cholesterol
      was observed in the unselected cohort after commencement of SGAs. One-third of
      children and adolescents had abnormal serum triglycerides and cholesterol;
      however, a dose-response was not demonstrated. Olanzapine and quetiapine had a
      greater increase in serum triglycerides. CONCLUSIONS: In addition to highlighting
      the need for routine screening for metabolic side effects in EOS, interventions
      to prevent and treat obesity and the metabolic syndrome are indicated.

PMID- 23968391
TI  - Nursing work: challenges for health management in the northeast of Brazil.
AB  - AIM: Social exchange theory is used as the framework to examine the interaction
      between supervisor-subordinate relationships, training and affective commitment
      for Northeast Brazilian public sector nursing professionals. BACKGROUND: There
      are continuing challenges to nursing management worldwide in terms of the supply
      of nursing professionals, their work relationships, nurse training and commitment
      to their employing organisations. The interplay between these factors for nurses
      in the Northeast of Brazil has not been well understood. METHOD: Quantitative
      data were collected from 550 nursing professionals using a cross-sectional,
      survey-base design. Qualitative data were collected from 25 participants using in
      depth interviews and focus group discussions. RESULT: Using path analysis, and
      the ordinary least squares approach, the findings demonstrated a significant, but
      weak, linkage between supervisor-subordinate relationships, training and
      organisational commitment. The qualitative data suggest that contracting out may
      be a causative factor. CONCLUSION: Healthcare managers in Brazil need to create
      more positive environments to strengthen supervisor-nurse relationships, improve
      the provision of training and to strengthen organisational commitment.
      IMPLICATIONS FOR NURSING MANAGEMENT: Healthcare policy-makers in hospital can
      make significant contributions to improving organisational commitment by reducing
      multiple job holding, improving the ratio of registered nurses to nursing
      technicians/assistants and beginning nurse supervision training in effective
      people management.

PMID- 23968392
TI  - Enzyme activity effects of N-terminal His-tag attached to catalytic sub-unit of
      phosphoinositide-3-kinase.
AB  - NTT (N-terminal tags) on the catalytic (p110) sub-unit of PI 3-K (phosphoinositol
      3-kinase) have previously been shown to increase cell signalling and oncogenic
      transformation. Here we test the impact of an NT (N-terminal) His-tag on in vitro
      lipid and protein kinase activity of all class-1 PI 3-K isoforms and two
      representative oncogenic mutant forms (E545K and H1047R), in order to elucidate
      the mechanisms behind this elevated signalling and transformation observed in
      vivo. Our results show that an NT His-tag has no impact on lipid kinase activity
      as measured by enzyme titration, kinetics and inhibitor susceptibility.
      Conversely, the NT His-tag did result in a differential effect on protein kinase
      activity, further potentiating the elevated protein kinase activity of both the
      helical domain and catalytic domain oncogenic mutants with relation to p110
      phosphorylation. All other isoforms also showed elevated p110 phosphorylation
      (although not statistically significant). We conclude that the previously
      reported increase in cell signalling and oncogenic-like transformation in
      response to p110 NTT is not mediated via an increase in the lipid kinase activity
      of PI 3-K, but may be mediated by increased p110 autophosphorylation and/or
      other, as yet unidentified, intracellular protein/protein interactions. We
      further observe that tagged recombinant protein is suitable for use in in vitro
      lipid kinase screens to identify PI 3-K inhibitors; however, we recommend that in
      vivo (including intracellular) experiments and investigations into the protein
      kinase activity of PI 3-K should be conducted with untagged constructs.

PMID- 23968394
TI  - Dermoscopic features of cerebriform intradermal nevus as secondary cutis verticis
      gyrata.

PMID- 23968395
TI  - The DNA binding domain of p53 is sufficient to trigger a potent apoptotic
      response at the mitochondria.
AB  - The tumor suppressor p53 is one of the most studied proteins in human cancer.1-3
      While nuclear p53 has been utilized for cancer gene therapy, mitochondrial
      targeting of p53 has not been fully exploited to date.4,5 In response to cellular
      stress, p53 translocates to the mitochondria and directly interacts with Bcl-2
      family proteins including antiapoptotic Bcl-XL and Bcl-2 and proapoptotic Bak and
      Bax.6 Antiapoptotic Bcl-XL forms inhibitory complexes with proapoptotic Bak and
      Bax preventing their homo-oligomerization.7 Upon translocation to the
      mitochondria, p53 binds to Bcl-XL, releases Bak and Bax from the inhibitory
      complex and enhances their homo-oligomerization.8 Bak and Bax homotetramer
      formation disrupts the mitochondrial outer membrane, releases antiapoptotic
      factors such as cytochrome c and triggers a rapid apoptotic response mediated by
      caspase induction.9 It is still unclear if the MDM2 binding domain (MBD), the
      proline-rich domain (PRD) and/or DNA binding domain (DBD) of p53 are the domains
      responsible for interaction with Bcl-XL.10-17 The purpose of this work is to
      determine if a smaller functional domain of p53 is capable of inducing apoptosis
      similarly to full length p53. To explore this question, different domains of p53
      (MBD, PRD, DBD) were fused to the mitochondrial targeting signal (MTS) from Bcl
      XL to ensure Bcl-XL specific targeting.18 The designed constructs were tested for
      apoptotic activity (TUNEL, Annexin-V, and 7-AAD) in 3 different breast cancer
      cell lines (T47D, MCF-7, MDA-MB-231), in a cervical cancer cell line (HeLa) and
      in non-small cell lung adenocarcinoma cells H1373. Our results indicate that DBD
      XL (p53 DBD fused to the Bcl-XL MTS) reproduces (in T47D cells) or demonstrates
      increased apoptotic activity (in MCF-7, MDA-MB-231, and HeLa cells) compared to
      p53-XL (full length p53 fused to Bcl-XL MTS). Additionally, mitochondrial
      dependent apoptosis assays (TMRE, caspase-9), co-IP and overexpression of Bcl-XL
      in T47D cells suggest that DBD fused to XL MTS may bind to and inhibit Bcl-XL.
      Taken together, our data demonstrates for the first time that the DBD of p53 may
      be the minimally necessary domain for achieving apoptosis at the mitochondria in
      multiple cell lines. This work highlights the role of small functional domains of
      p53 as a novel cancer biologic therapy. 

PMID- 23968396
TI  - Rational design of a photomagnetic chain: bridging single-molecule magnets with a
      spin-crossover complex.
AB  - The spin-crossover complex [Fe(LN5)(CN)2].H2O (1, LN5 = 2,13-dimethyl-3,6,9-12,18
      pentaazabicyclo[12.3.1]octadeca-1(18),2,12,14,16-pentaene), reported previously
      by Nelson et al. in 1986, was reinvestigated, and its structure determined by
      single crystal X-ray diffraction for the first time. The reaction between
      [Mn(III)(saltmen)(H2O)](+) and this photomagnetic linker yielded the trinuclear
      molecular complex [{Mn(saltmen)}2FeHS(LN5)(CN)2](ClO4)2.0.5CH3OH (2) and the one
      dimensional compound [{Mn(saltmen)}2FeLS(LN5)(CN)2](ClO4)2.0.5C4H10O.0.5H2O (3)
      depending on the addition order of the reagents (HS: High-Spin; LS: Low-Spin).
      Compound 3 exhibits a wave-shaped chain structure built from the assembly of the
      trinuclear [Mn(III)-NC-Fe(II)] motif found in 2. Static magnetic measurements
      revealed the existence of antiferromagnetic Mn(III)...Fe(II) (Fe(II) HS, S = 2)
      interactions in the trinuclear entity of 2 via the cyanido bridge leading to an
      ST = 2 ground state. In the case of 3, concomitant ferromagnetic and
      antiferromagnetic exchange interactions are found along the chain due to the
      presence of two crystallographically independent {Mn2(saltmen)2} units, which
      behave differently as shown by the magnetic susceptibility analysis, while the
      Fe(II) (LS, S = 0) cyanido-bridging moiety is isolating these dinuclear Mn(III)
      units. ac susceptibility experiments indicated slow relaxation of the
      magnetization arising from the ferromagnetically coupled [Mn2] units (tau0 = 1.1
      * 10(-7) s and Delta(eff)/k(B) = 13.9 K). Optical reflectivity and photomagnetic
      properties of 1 and 3 have been investigated in detail. These studies reveal that
      the photomagnetic properties of 1 are kept after its coordination to the acceptor
      Mn(III)/saltmen complexes, allowing in 3 to switch "on" and "off" the magnetic
      interaction between the photoinduced Fe(II) HS unit (S = 2) and the Mn(III) ions.
      To the best of our knowledge, the compound 3 represents the first example of a
      coordination network of single-molecule magnets linked by spin-crossover units
      inducing thermally and photoreversible magnetic and optical properties.

PMID- 23968397
TI  - Photocurrent mapping of 3D CdSe/CdTe windowless solar cells.
AB  - This paper details the use of scanning photocurrent microscopy to examine
      localized current collection efficiency of thin-film photovoltaic devices with in
      plane patterning at a submicrometer length scale. The devices are based upon two
      interdigitated comb electrodes at the micrometer length scale prepatterned on a
      substrate, with CdSe electrodeposited on one electrode and CdTe deposited over
      the entire surface of the resulting structure by pulsed laser deposition.
      Photocurrent maps provide information on what limits the performance of the
      windowless CdSe/CdTe thin-film photovoltaic devices, revealing "dead zones"
      particularly above the electrodes contacting the CdTe which is interpreted as
      recombination over the back contact. Additionally, the impact of ammonium sulfide
      passivation is examined, which enables device efficiency to reach 4.3% under
      simulated air mass 1.5 illumination. 

PMID- 23968398
TI  - A metabolomic study to identify new globotriaosylceramide-related biomarkers in
      the plasma of Fabry disease patients.
AB  - Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of
      the enzyme alpha-galactosidase A, which results in the progressive accumulation
      of glycosphingolipids. In addition to the two biomarkers, globotriaosylceramide
      (Gb3) and globotriaosylsphingosine (lyso-Gb3), which are routinely used for
      detection and high-risk screening of Fabry disease patients, novel urinary Gb3
      related isoforms/analogues as well as newly defined lyso-Gb3 analogues in plasma
      and urine from Fabry patients have recently been described by our group. The aim
      of this study was to extend our recent analyses to identify and evaluate new
      potential Gb3-related biomarkers in the plasma of untreated male Fabry disease
      patients using a mass spectrometry metabolomic approach. A multivariate
      statistical analysis revealed five Gb3-related novel biomarkers in the plasma of
      male Fabry patients. Three of these new biomarkers correspond to Gb3, which has
      an extra double bond on the sphingosine with C16:0, C18:0, and C22:1 fatty acid
      chains. The fourth biomarker corresponds to a mixture of two structural isomers,
      the first with a d16:1 sphingosine and a C16:0 fatty acid and the second with a
      d18:1 sphingosine and a C14:0 fatty acid. To our knowledge, it is the first time
      that a Gb3 analogue with a d16:1 sphingosine moiety has been reported. In
      addition, this Gb3 analogue was also present in its methylated form. These
      biomarkers are part of a metabolic profile that may provide insight into the
      pathophysiology of Fabry disease. 

PMID- 23968399
TI  - Rate constant and branching fraction for the NH2 + NO2 reaction.
AB  - The NH2 + NO2 reaction has been studied experimentally and theoretically. On the
      basis of laser photolysis/LIF experiments, the total rate constant was determined
      over the temperature range 295-625 K as k1,exp(T) = 9.5 * 10(-7)(T/K)(-2.05) exp(
      404 K/T) cm(3) molecule(-1) s(-1). This value is in the upper range of data
      reported for this temperature range. The reactions on the NH2 + NO2 potential
      energy surface were studied using high level ab initio transition state theory
      (TST) based master equation methods, yielding a rate constant of k1,theory(T) =
      7.5 * 10(-12)(T/K)(-0.172) exp(687 K/T) cm(3) molecule(-1) s(-1), in good
      agreement with the experimental value in the overlapping temperature range. The
      two entrance channel adducts H2NNO2 and H2NONO lead to formation of N2O + H2O
      (R1a) and H2NO + NO (R1b), respectively. The pathways through H2NNO2 and H2NONO
      are essentially unconnected, even though roaming may facilitate a small flux
      between the adducts. High- and low-pressure limit rate coefficients for the
      various product channels of NH2 + NO2 are determined from the ab initio TST-based
      master equation calculations for the temperature range 300-2000 K. The
      theoretical predictions are in good agreement with the measured overall rate
      constant but tend to overestimate the branching ratio defined as beta = k1a/(k1a
      + k1b) at lower temperatures. Modest adjustments of the attractive potentials for
      the reaction yield values of k1a = 4.3 * 10(-6)(T/K)(-2.191) exp(-229 K/T) cm(3)
      molecule(-1) s(-1) and k1b = 1.5 * 10(-12)(T/K)(0.032) exp(761 K/T) cm(3)
      molecule(-1) s(-1), in good agreement with experiment, and we recommend these
      rate coefficients for use in modeling. 

PMID- 23968400
TI  - Association of circulating levels of nicotinamide phosphoribosyltransferase
      (NAMPT/Visfatin) and of a frequent polymorphism in the promoter of the NAMPT gene
      with coronary artery disease in diabetic and non-diabetic subjects.
AB  - BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT) is the limiting enzyme
      in one of pathways of synthesis of Nicotinamide Adenine Dinucleotide, a redox
      coenzyme. NAMPT is considered as an insulin-mimetic factor and a potential
      regulatory factor in inflammatory and immune processes. Associations of
      circulating NAMPT levels with cardiovascular disease (CVD) and insulin resistance
      have been reported. We investigated association of circulating NAMPT levels and
      the rs9770242 NAMPT gene polymorphism with coronary artery disease (CAD).
      METHODS: We studied 594 Brazilian subjects undergoing a coronary angiography (49%
      of whom had type 2 diabetes). CAD, defined as stenosis greater than 50% in one
      major coronary vessel or branch, was observed in 68% of subjects. Genetic studies
      were also performed in 858 North-American Non-Hispanic White subjects with type 2
      diabetes (49% with CAD). RESULTS: We observed an interaction between glycemic and
      CAD status on the comparison of NAMPT levels by CAD status. NAMPT levels were
      higher in type 2 diabetic patients with CAD as compared to those without CAD:
      5.27 +/- 2.93 ng/ml vs. 4.43 +/- 2.94 ng/ml, p = 0.006 (mean +/- SD). NAMPT
      levels were not significantly different in non-diabetic subjects with or without
      CAD. The T-allele of rs9770242 was associated with CAD in the Brazilian cohort
      (OR 1.46, 95% CI 1.06 - 2.01, p = 0.02) while no association was observed in the
      North-American cohort. CONCLUSIONS: Our data suggest that circulating NAMPT
      levels are associated with CAD in type 2 diabetic patients. NAMPT rs9770242
      polymorphism may be associated with CAD in some populations.

PMID- 23968401
TI  - Functional Val66Met polymorphism of Brain-derived neurotrophic factor in type 2
      diabetes with depression in Han Chinese subjects.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been implicated in the
      pathogenesis of major depression. Individuals with type 2 diabetes (T2DM) have a
      high prevalence of major depression and low levels of BDNF. We therefore explored
      whether the BDNF Val66Met polymorphism is associated with co-morbid depression
      and whether depression affects the serum levels of BDNF in a Han Chinese subjects
      with T2DM. METHODS: A Total of 296 T2DM patients and 70 healthy volunteers
      (Health control, HC group) were recruited in this study. T2DM patients were
      divided into two subgroups: depressive diabetes group (DDM group, n = 64) and non
      depressive diabetes group (NDDM group, n = 232), according to the presence or the
      absence of depression assessed by Center for Epidemiologic Studies Depression
      Scale (CES-D) and Patient Health Questionnaire-9 (PHQ-9). Val66Met polymorphism
      was detected by polymerase chain reaction-restriction fragment length
      polymorphism analysis (PCR-RFLP). Serum BDNF levels were measured by ELISA kit.
      RESULTS: In this study, 21.6% (64/296) patients with T2DM had depression. The
      BDNF Val66Met genotype distributions were statistically different among the three
      groups (chi2 = 7.39, p < 0.05). DDM group carried the highest frequencies of Met
      allele (53.9%) compared to HC group (39.3%) and NDDM group (38.8%). Subjects with
      Met/Met had lowest serum BDNF levels (76.59 +/- 5.12 pg/ml, F = 7.39, p < 0.05)
      compared to subjects with Val/Met (79.04 +/- 5.19 pg/ml) and Val/Val (83.83 +/-
      3.97 pg/ml). Within T2DM group, it was also observed that the serum BDNF levels
      in DDM group were significantly lower than those in NDDM group (76.67 +/- 5.35
      vs. 79.84 +/- 3.97 pg/ml, p < 0.05). In type 2 diabetes subjects, BDNF serum
      levels were significant correlations with genotypes (r = -0.346, p < 0.01),
      depression scores (r = -0.486, p < 0.01) and HbA1c (r = -0.168, p < 0.05). After
      adjustment for gender, HbA1c, BMI and numbers of complications, BDNF Val/Met
      genotype distributions (OR = 2.105, p < 0.05) and decreased serum BDNF levels (OR
      = 0.835, p < 0.01) were independently associated with depression in T2DM.
      CONCLUSIONS: The BDNF Val66Met polymorphism might be implicated in the
      pathogenesis of depression in T2DM by decreasing serum BDNF levels in Han Chinese
      Subjects.

PMID- 23968402
TI  - What is the current status of training and practice of early intervention in
      psychiatry? Results from a survey in 35 countries.
AB  - AIM: To assess: (i) trainees' educational needs on early intervention in
      psychiatry; (ii) their satisfaction and competence in early detection and
      management of patients with severe mental disorders; (iii) characteristics of
      training on prevention and on early intervention in psychiatry; and (iv)
      organizational and clinical differences of early intervention programmes and
      services in different countries. METHODS: Sixty early career psychiatrists,
      recruited from the early career psychiatrists' network of the World Psychiatric
      Association, were invited to participate in the survey. Respondents were asked to
      provide the collective input of their trainees' association rather than that of
      any individual officer or member. An online survey was conducted using an ad hoc
      questionnaire consisting of 18 items. RESULTS: Thirty-five countries sent back
      the questionnaire (58.3%). University training in early intervention for mental
      disorders was provided in 13 countries (38%); 54% of respondents were not
      satisfied with received training and about half of them did not feel enough
      confident to provide specialistic interventions to patients at the onset of the
      disorder. Services for early intervention existed in 22 countries (63%). The most
      frequently available were those for schizophrenia (75%). Informative campaigns on
      mental disorders were usually carried out in almost all surveyed countries (85%).
      CONCLUSIONS: Although prevention and early intervention represent one of the
      current paradigms of psychiatric practice and research, efforts are still needed
      in order to improve training programmes at university sites.

PMID- 23968403
TI  - Association of HLA-DRB1 and -DQB1alleles and haplotypes with rheumatoid arthritis
      in a Pakistani population.
AB  - INTRODUCTION: Rheumatoid arthritis is an autoimmune disease with poorly
      understood pathophysiology. Genetic components of disease etiology, especially
      human leukocyte antigen (HLA) associations, are well known. Ethnic differences
      account for a number of variations in disease association with the HLA locus and
      there seem to be differences in various studies regarding its genetic
      predisposition. This study was aimed at determining the contribution of DRB1 and
      DQB1 components of HLA class II in rheumatoid arthritis in a Pakistani cohort.
      METHOD: For this study, 110 patients and 120 healthy controls from the same
      geographical area and matched ethnicity were enrolled. Blood DNA was isolated
      from all the subjects and HLA alleles were typed following allele specific
      amplification. Subsequently, haplotypes were generated and allelic and haplotype
      distribution frequencies were compared among the patients and controls using chi2
      and Arlequin software. The data obtained by this analysis were also compared with
      other reported associations found in the Pakistani population by meta-analysis.
      RESULTS: HLA allelic status was determined among the patients and controls from
      the same geographical area to account for differences in ethnicity and
      environmental factors. Significant associations were found for alleles as well as
      haplotypes among the patients of rheumatoid arthritis. DRB1*10, DQB1*05 and
      DQB1*602 were found to be associated with disease susceptibility, whereas DRB1*11
      and DQB1*02 had protective effect against the disease. Similarly, haplotype
      DRB1*10-DQB1*05 was associated disease risk, whereas DRB1*07-DQB1*02 and DRB1*11
      DQB1*0301 had a protective effect. CONCLUSION: There is a significant DRB1and
      DQB1 allele and haplotype association with rheumatoid arthritis susceptibility
      and protection.

PMID- 23968405
TI  - Editor's Note:.

PMID- 23968404
TI  - Prosequence switching: an effective strategy to produce biologically active E.
      coli heat-stable enterotoxin STh.
AB  - Enterotoxigenic Escherichia coli (ETEC) infections account for the majority of
      cases of acute secretory diarrhea. The causative agents are enterotoxins secreted
      by ETEC, among them is the heat-stable enterotoxin, STh. STh is a 19-amino acid
      peptide containing three disulfide bonds that stimulates fluid secretion in the
      bowel by binding to the receptor domain of intestinal guanylyl cyclase C (GC-C).
      Since GC-C agonists have pharmacologic potential for diagnosis and treatment of
      disorders such as constipation-predominant irritable bowel syndrome (IBS-C),
      chronic constipation, and colorectal carcinoma, it is crucial to develop methods
      for the large-scale production of STh and related peptides. Here, we present a
      strategy for recombinant expression of STh that relies on the use of the
      prosequence of human uroguanylin to support proper folding and disulfide bond
      formation. The chimeric protein CysCys-STh consisting of the propeptide of
      uroguanylin as N-terminus and the STh peptide as C-terminus was expressed in E.
      coli, and an efficient purification protocol was developed. Trypsin digestion of
      this protein released the enterotoxin which could be obtained in high purity. NMR
      and mass spectrometry confirmed the identity and homogeneity of the toxin, and
      its biological activity was confirmed by a cell-based in vivo assay. The
      expression scheme introduced here represents a cost-efficient and scalable way of
      STh production.

PMID- 23968406
TI  - Static and dynamic aspects of cortical somatotopy: a critical evaluation.
AB  - The demonstration that functional somatotopic maps within the adult neocortex
      undergo some degree of reorganization following peripheral injury has aroused
      considerable interest. The evidence for such reorganization in the rat and monkey
      is reviewed and it is concluded that in both species there is good evidence for
      limited functional map reorganization in the adult neocortex following peripheral
      injury. The significance of such functional map reorganization, particularly in
      terms of whether or not cortical maps are continuously modifiable throughout
      life, is discussed. It is concluded that the current evidence for map
      reorganization is best interpreted in terms of the unmasking of preexisting
      neuronal circuits rather than as evidence of dynamic cortical selection
      processes. 

PMID- 23968407
TI  - Behavioral Indices of Multisensory Integration: Orientation to Visual Cues is
      Affected by Auditory Stimuli.
AB  - Physiological studies have demonstrated that inputs from different sensory
      modalities converge on, and are integrated by, individual superior colliculus
      neurons and that this integration is governed by specific spatial rules. The
      present experiments were an attempt to relate these neural processes to overt
      behavior by determining if behaviors believed to involve the circuitry of the
      superior colliculus would show similar multisensory dependencies and be subject
      to the same rules of integration. The neurophysiological-behavioral parallels
      proved to be striking. The effectiveness of a stimulus of one modality in
      eliciting attentive and orientation behaviors was dramatically affected by the
      presence of a stimulus from another modality in each of the three behavioral
      paradigms used here. Animals trained to approach a low intensity visual cue had
      their performance significantly enhanced when a brief, low intensity auditory
      stimulus was presented at the same location as the visual cue, but their
      performance was significantly depressed when the auditory stimulus was disparate
      to it. These effects were independent of the animals' experience with the
      modifying (i.e. auditory) stimulus and exceeded what might have been predicted
      statistically based on the animals' performance with each single-modality cue.
      The multiplicative nature of these multisensory interactions and their dependence
      on the relative positions and intensities of the two stimuli were all very
      similar to those observed physiologically for single cells. The few differences
      that were observed appeared to reflect the fact that understanding integration at
      the level of the single cell requires reference to the individual cell's
      multisensory receptive field properties, while at the behavioral level
      populations of receptive fields must be evaluated. These data illustrate that the
      rules governing multisensory integration at the level of the single cell also
      predict responses to these stimuli in the intact behaving organism. 

PMID- 23968408
TI  - The Effects of Focal Brain Damage on Sentence Processing: an examination of the
      neurological organization of a mental module.
AB  - The effects of prior semantic context upon lexical access during sentence
      processing were examined for three groups of subjects; nonfluent agrammatic
      (Broca's) aphasic patients; fluent (Wernicke's) aphasic patients; and
      neurologically intact control patients. Subjects were asked to comprehend
      auditorily presented, structurally simple sentences containing lexical
      ambiguities, which were in a context strongly biased toward just one
      interpretation of that ambiguity. While listening to each sentence, subjects also
      had to perform a lexical decision task upon a visually presented letter string.
      For the fluent Wernicke's patients, as for the controls, lexical decisions for
      visual words related to each of the meanings of the ambiguity were facilitated.
      By contrast, agrammatic Broca's patients showed significant facilitation only for
      visual words related to the a priori most frequent interpretation of the
      ambiguity. On the basis of these data, we suggest that normal form-based word
      retrieval processes are crucially reliant upon the cortical tissue implicated in
      agrammatism, but that even the focal brain damage yielding agrammatism does not
      destroy the normally encapsulated form of word access. That is, we propose that
      in agrammatism, the modularity of word access during sentence comprehension is
      rendered less efficient but not lost. Additionally, we consider a number of
      broader issues involved in the use of pathological material to infer
      characteristics of the neurological organization of cognitive architecture. 

PMID- 23968409
TI  - An electrophysiological probe of incidental semantic association.
AB  - Long-latency components of event-related brain potentials (ERPs) recorded from
      subjects reading meaningful text are sensitive to semantic relationships among
      the major lexical items of sentences. In particular, the N400 components are
      enlarged to words that are semantically unrelated to or incongruous with the
      context provided by preceding items in a sentence. The present experiment was
      aimed at finding out whether this inverse relationship between N400 amplitude and
      semantic association would extend to situations where words were presented in
      isolated pairs, using a design that dissociated changes in N400 from confounding
      ERP waves elicited by active decision making. KRP's were recorded to 320 word
      pairs presented to eleven subjects. Each pair of words was followed by a letter,
      and subjects made a differential response according to whether or not the letter
      had been present in either of the words. After the ERP recording session,
      subjects rated the degree of semantic association between the words in each pair.
      ERP averages were formed on the basis of the subjects' ratings and on the basis
      of normative, a priori categories. For both types of averages the N400 amplitude
      was found to be a sensitive index of semantic association, even though the
      association was incidental to the subject's assigned task. These findings suggest
      the utility of the N400 measure in studies of semantic priming and as a probe of
      the automaticity of contextual influences in language processing. 

PMID- 23968410
TI  - Is word recognition automatic? A cognitive-anatomical approach.
AB  - What are the implications of anatomical localization of component mental
      operations for cognitive models? In this paper we use the anatomical
      localizations of visual and auditory word processing that were previously
      reported from PET studies (Petersen, Fox, Posner, Mintun & Raichle, 1988. We
      hypothesize that two operations performed simultaneously by the same or heavily
      interconnected anatomical areas will produce specific interference. One task is
      repeating back (shadowing) auditory words as quickly as possible. This task is
      shown to interfere with shifts of visual attention in the direction of peripheral
      cues. Both tasks are known to require common attentional operations localized to
      the medial frontal lobe. The shadowing task does not interfere with operations
      involving priming of a visual word form. This kind of priming involves areas of
      the ventral occipital lobe not used during shadowing. Finally, both shadowing and
      semantic priming involve anterior semantic and intentional areas. Accordingly,
      they can interfere. The conditions under which they produce interference suggest
      that the interference involves operations performed by the anterior attention
      system. These experiments support the idea that words automatically activate
      visual word forms, but involve shared attentional systems for higher level
      processes. 

PMID- 23968411
TI  - Derivation of Encoding Characteristics of Layer II Cerebral Cortex.
AB  - Computer simulations of layers I and II of pirifonn (olfactory) cortex indicate
      that this biological network can generate a series of distinct output responses
      to individual stimuli, such that different responses encode different levels of
      information about a stimulus. In particular, after learning a set of stimuli
      modeled after distinct groups of odors, the simulated network's initial response
      to a cue indicates only its group or category, whereas subsequent responses to
      the same stimulus successively subdivide the group into increasingly specific
      encoding of the individual cue. These sequences of responses amount to an
      automated organization of perceptual memories according to both their
      similarities and differences, facilitating transfer of learned information to
      novel stimuli without loss of specific information about exceptions. Human
      recognition performance robustly exhibits such multiple levels: a given object
      can be identified as a vehicle, as an automobile, or as a Mustang. The findings
      reported here suggest that a function as apparently complex as hierarchical
      recognition memory, which seems suggestive of higher 'cognitive' processes, may
      be a fundamental intrinsic property of the operation of this single cortical cell
      layer in response to naturally-occurring inputs to the structure. We offer the
      hypothesis that the network function of superficial cerebral conical layers may
      simultaneously acquire and hierarchically organize information about the
      similarities and differences among perceived stimuli. Experimental manipulation
      of the simulation has generated hypotheses of direct links between the values of
      specific biological features and particular attributes of behavior, generating
      testable physiological and behavioral predictions. 

PMID- 23968412
TI  - Brainprints: Computer-Generated Two-Dimensional Maps of the Human Cerebral Cortex
      in vivo.
AB  - We describe an in vivo method for the quantitative analysis of human necrotical
      anatomy. The technique allows unfolded regions of functional and morphological
      interest to be measured planimetrically. Two-dimensional cortical maps and
      surface area determinations derived from magnetic resonance images of monozygotic
      twins are presented. In addition, reconstructions and measurements of published
      post-mortem human and rhesus monkey hemispheres are reported. Potential
      applications for the study of brain organization in relation to cognitive, motor,
      and perceptual performance in normal and neurological populations are considered.

PMID- 23968432
TI  - Natural product derived antiprotozoal agents: synthesis, biological evaluation,
      and structure-activity relationships of novel chromene and chromane derivatives.
AB  - Various natural products with the chromane and chromene scaffold exhibit high
      antiprotozoal activity. The natural product encecalin (7) served as key
      intermediate for the synthesis of different ethers 9, amides 11, and amines 12.
      The chromane analogues 14 and the phenols 15 were obtained by reductive amination
      of ketones 13 and 6, respectively. Angelate 3, ethers 9, and amides 11 did not
      show considerable antiprotozoal activity. However, the chromene and chromane
      derived amines 12, 14, and 15 revealed promising antiprotozoal activity and
      represent novel lead compounds. Whereas benzylamine 12a and alpha
      methylbenzylamine 12g were active against P. falciparum with IC50 values in the
      range of chloroquine, the analogous phenols 15a and 15b were unexpectedly 10- to
      25-fold more potent than chloroquine with selectivity indexes of 6760 and 1818,
      respectively. The phenylbutylamine 14d based on the chromane scaffold has
      promising activity against T. brucei rhodesiense and L. donovani. 

PMID- 23968433
TI  - Multidimensional structure of the Groningen Frailty Indicator in community
      dwelling older people.
AB  - BACKGROUND: Due to the rapidly increasing number of older people worldwide, the
      prevalence of frailty among older adults is expected to escalate in coming
      decades. It is crucial to recognize early onset symptoms to initiate specific
      preventive care. Therefore, early detection of frailty with appropriate screening
      instruments is needed. The aim of this study was to evaluate the underlying
      dimensionality of the Groningen Frailty Indicator (GFI), a widely used self
      report screening instrument for identifying frail older adults. In addition,
      criterion validity of GFI subscales was examined and composition of GFI scores
      was evaluated. METHODS: A cross-sectional study design was used to evaluate the
      structural validity, internal consistency and criterion validity of the GFI
      questionnaire in older adults aged 65 years and older. All subjects completed the
      GFI questionnaire (n = 1508). To assess criterion validity, a smaller sample of
      119 older adults completed additional questionnaires: De Jong Gierveld Loneliness
      Scale, Hospital Anxiety Depression Scale, RAND-36 physical functioning, and
      perceived general health item of the EuroQol-5D. Exploratory factor analysis and
      Mokken scale analysis were used to evaluate the structural validity of the GFI. A
      Venn diagram was constructed to show the composition of GFI subscale scores for
      frail subjects. RESULTS: The factor structure of the GFI supported a three
      dimensional structure of the scale. The subscales Daily Activities and
      Psychosocial Functioning showed good internal consistency, scalability, and
      criterion validity (Daily Activities: Cronbach's alpha = 0.81, H(s) = .84, r = 
      .62; Psychosocial Functioning: Cronbach's alpha = 0.80, H(s) = .35, r = -.48).
      The subscale Health Problems showed less strong internal consistency but
      acceptable scalability and criterion validity (Cronbach's alpha = .57, H(s) =
      .35, r = -.48). The present data suggest that 90% of the frail older adults
      experience problems in the Psychosocial Functioning domain. CONCLUSIONS: The
      present findings support a three-dimensional factor structure of the GFI,
      suggesting that a multidimensional assessment of frailty with the GFI is
      possible. These GFI subscale scores produce a richer assessment of frailty than
      with a single overall sum GFI score, and likely their use will contribute to more
      directed and customized care for older adults.

PMID- 23968434
TI  - Port-site metastases following robot-assisted laparoscopic surgery for
      gynecological malignancies.
AB  - OBJECTIVE: To evaluate the incidence and possible predictors associated with port
      site metastases following robotic surgery. DESIGN: Prospective study. SETTING:
      University Hospital. POPULATION: Women with gynecological cancer. METHODS: The
      occurrence of port-site metastases in the first 475 women undergoing robotic
      surgery for gynecological cancer was reviewed. MAIN OUTCOME MEASURES: Rate of
      port-site metastases. RESULTS: A port-site metastasis was detected in nine of 475
      women (1.9%). Eight women had either an unexpected locally advanced disease or
      lymph-node metastases at the time of surgery. All nine women received
      postoperative adjuvant therapy. Women with >= stage III endometrial cancer and
      women with node positive cervical cancer had a significantly higher risk of
      developing a port-site metastasis, as did women with high-risk histology
      endometrial cancer. Port-site metastases were four times more likely to occur in
      a specimen-retrieval port. One (0.2%) isolated port-site metastasis was detected.
      The median time to occurrence of a port-site metastasis was 6 months (range 2-19
      months). Six of the nine women (67%) have died and their median time of survival
      from recurrence was 4 months (range 2-16 months). CONCLUSION: In women with
      gynecological cancer, the incidence of port-site metastases following robotic
      surgery was 1.9%. High-risk histology and/or advanced stage of disease at surgery
      seem to be contributing factors.

PMID- 23968435
TI  - Protected but accessible: oxygen activation by a calixarene-stabilized undecagold
      cluster.
AB  - DFT computations show that calixarenes stabilize subnanometer Au11 clusters
      allowing access of small molecules like O2 to reactive metal sites in the core.
      Maximum of three dioxygen molecules can bind to the cluster, and they are
      activated to a superoxo O2(-) state. This study predicts that gold clusters could
      act as viable oxidation catalysts at ambient conditions based on similar
      principles as the metal centers in enzymes. 

PMID- 23968436
TI  - Micromolding in capillaries for calcination-free fabrication of flexible
      inorganic phosphor films consisting of rare-earth-ion-doped nanoparticles.
AB  - We discuss the micromolding in capillaries technique for the direct fabrication
      of calcination-free rare earth ion-doped (RE) phosphor films consisting of RE
      nanoparticles on plastic sheets. We synthesized two types of RE nanoparticles
      consisting of Y2O3 matrix doped with Er and Yb ions. Green upconversion
      luminescence, red upconversion luminescence, and near-infrared fluorescence
      appeared from the RE nanoparticles under excitation of near-infrared light.
      Adjusting the channel width and depth of polydimethylsiloxane molds led to
      control of the density of nanoparticles in the patterned RE nanoparticle films.
      Adjusting concentration of the RE nanoparticle dispersion and size of the RE
      nanoparticles allowed for the control of the density of nanoparticles in the
      patterned RE nanoparticle films. The density of nanoparticles in the patterned RE
      films on plastic sheets increased with an increase in the number of injection and
      drying of the RE nanoparticle dispersion. These results demonstrate that this
      technique enables us to directly fabricate the patterned RE phosphor films on
      plastic sheets, leading to the fabrication of inorganic flexible devices with
      small fabrication steps and material consumptions. 

PMID- 23968437
TI  - What's in this issue?

PMID- 23968438
TI  - Yes, but how do I know what I don't know? Moving towards conscious competence in
      end-of-life care.

PMID- 23968439
TI  - Re-exploring the ritual of the ward round.

PMID- 23968440
TI  - Ventilator auto-cycling from cardiogenic oscillations: case report and review of
      literature.
AB  - BACKGROUND: Brain death is the total loss of all brain and brain stem functions,
      and its diagnosis is often confirmed by an apnoea test, which relies on
      disconnecting the patient from the ventilator. Auto-triggering or auto-cycling is
      defined as a ventilator being triggered in the absence of patient effort,
      intrinsic respiratory drive or inspiratory muscle activity. Ventilator auto
      triggering could delay the diagnosis of brain death leading to unnecessary
      admission for the patient and false hopes of recovery for the family. METHODS: We
      report a case of ventilator auto-triggering associated with cardiogenic
      oscillations in a female patient. RESULTS: We confirmed the finding of ventilator
      auto-triggering by changing the patient's position and reassessing the triggering
      thresholds. Brain death was then confirmed by apnoea test. CONCLUSION: This case
      is presented to arouse the awareness of the medical staff and nurses to this
      phenomenon, which can mimic an intrinsic respiratory effort in patients allegedly
      diagnosed with brain death. Along with this case report, we review the English
      language publications for similar cases.

PMID- 23968441
TI  - Critical care research in a district general hospital: the first year.
AB  - Until recently, research in critical care units has usually taken place in
      university teaching hospitals. The 'general' critical care unit patient
      population is broader than this and the research needs to reflect this. As a
      general critical care unit in a district general hospital we wanted to set-up
      research within our own department, as part of the critical care team and part of
      our culture. With extensive background communication, drive and hard work, the
      support of the hospital Research and Development department was gained and
      Comprehensive Local Research Network funding successfully applied for. A research
      team was established and a model for the Research Nurse role was developed and
      implemented. This model is described. Participation in national trials commenced
      and the research portfolio is growing. Networking with other teams also proved
      valuable. Research has been established as part of the 'culture' of the day-to
      day work and the staff have embraced this. Dedicated Research Nurse posts and
      education of the whole team have ensured successful implementation and
      recruitment of the studies. Experiences of the first year are shared and
      discussed here. Sharing experience of developing research within a critical care
      unit in a district general hospital, and a suggested model for a new Research
      Nurse role, may benefit other similar units in their efforts to establish
      research. 

PMID- 23968442
TI  - Nursing challenges with a severely injured patient in critical care.
AB  - BACKGROUND: Patients with severe, multiple, traumatic injuries are challenging to
      manage in critical care. Early identification of injuries and optimal
      resuscitation is essential for favourable outcomes. Trauma-related haemorrhage
      can lead to the lethal triad of hypothermia, coagulopathy and acidosis. Many
      trauma patients require urgent haemorrhage control and structural fixation
      through operative intervention. However, metabolic derangement and cardiovascular
      instability may delay surgery, resulting in an ongoing cycle of deterioration.
      Damage control surgery (DCS) may be used as a temporizing measure until the
      patient is stabilized in critical care. The aim of this case study is to discuss
      the complex issues faced in the critical care management of a severely injured
      patient. DESIGN: We conducted a patient case study, with analysis of care using
      published evidence. The key terms used to search for evidence were trauma,
      injury, damage control surgery, spinal fixation, critical/intensive care and
      nurse. RESULTS: We report the care of a trauma patient with complex, conflicting
      injuries requiring management of the lethal triad and DCS. The delay in
      subsequent definitive repair of spinal column fractures provided many challenges
      for critical care nurses including restricted patient mobilization, positioning
      and pressure ulcer prevention. A review of contemporary evidence relating to DCS
      reveals that whilst this technique is used increasingly in trauma, the research
      focuses on single system injuries. CONCLUSION: Evidence and guidelines are
      required to support DCS for critical care patients with multiple, conflicting
      injuries including spinal fractures. For patients with delayed surgical
      intervention, rotational bed therapy may assist critical care nurses in meeting
      needs.

PMID- 23968443
TI  - Central venous oxygen saturation: analysis, clinical use and effects on
      mortality.
AB  - AIMS AND OBJECTIVES: The aim of this literature review was to provide a clear
      definition of central venous oxygen saturation (ScvO2), highlight the differences
      between ScvO2 and mixed venous oxygen saturation (SvO2), show how it can be used
      clinically and the effect central venous oxygen saturation has on mortality.
      BACKGROUND: Many articles concentrate on the individual aspects of ScvO2, such as
      its use in early goal-directed therapy, but few provide a full overview of what
      it means, how to interpret results and how it can be used clinically. SEARCH
      STRATEGIES: Keywords were searched for including central venous oxygen saturation
      ScvO2 mixed venous oxygen saturations ScvO2 early goal-directed therapy sepsis
      and mortality. Where possible only publications within the last 10 years were
      used but key publications were not excluded if they were out with this time
      frame. CONCLUSIONS: Central venous oxygen saturation (ScvO2) is a very important
      measurement which can be easily taken in a critical care environment by both
      medical and nursing staff. It provides an understanding of the patient's oxygen
      delivery, oxygen consumption and cardiac output. It has a key role within early
      goal-directed therapy and has been shown to decrease mortality when taken and
      analysed appropriately. RELEVANCE TO CLINICAL PRACTICE: This literature review
      will highlight to nursing staff within the critical care environment the
      importance of central venous oxygen saturation measurement and interpretation. By
      raising awareness of the importance of this measurement it is hoped nursing staff
      will be proactive in both taking this test and analysing the results, therefore
      facilitating better care for the septic, critically ill patient and improving
      outcomes for these patients.

PMID- 23968444
TI  - Critical care nurses' experiences of nursing mothers in an ICU after complicated
      childbirth.
AB  - BACKGROUND: Providing nursing care for a critically ill obstetric patient or a
      patient who has just become a mother after a complicated birth can be a
      challenging experience for critical care nurses (CCNs). These patients have
      special needs because of the significant alterations in their physiology and
      anatomy together with the need to consider such specifics as breastfeeding and
      mother-child bonding. AIM: The aim with this study was to describe CCNs'
      experience of nursing the new mother and her family after a complicated
      childbirth. METHOD: The design of the study was qualitative. Data collection was
      carried out through focus group discussions with 13 CCNs in three focus groups
      during spring 2012. The data were subjected to qualitative content analysis.
      FINDINGS: The analysis resulted in the formulation of four categories: the mother
      and her vital functions are prioritized; not being responsible for the child and
      the father; an environment unsuited to the new family and collaboration with
      staff in neonatal and maternity delivery wards. CONCLUSION AND RELEVANCE TO
      CLINICAL PRACTICE: When nursing a mother after a complicated birth the CCNs give
      her and her vital signs high priority. The fathers of the children or partners of
      the mothers are expected to take on the responsibility of caring for the newborn
      child and of being the link with the neonatal ward. It is suggested that
      education about the needs of new families for nursing care would improve the
      situation and have clinical implications. Whether the intensive care unit is
      always the best place in which to provide care for mothers and new families is
      debatable.

PMID- 23968451
TI  - Cooling and Auger recombination of charges in PbSe nanorods: crossover from cubic
      to bimolecular decay.
AB  - The cooling and Auger recombination of electron-hole pairs in PbSe quantum dots
      (QDs) and a series of nanorods (NRs) with similar diameter and varying length was
      studied by ultrafast pump-probe laser spectroscopy. Hot exciton cooling rates are
      found to be independent of nanocrystal shape. The energy relaxation rate
      decreases during cooling of charges, due to reduction of the density of
      electronic states. Auger recombination occurs via cubic third-order kinetics of
      uncorrelated charges in the QDs and NRs with length up to 29 nm. On increasing
      the NR length to 52 nm, a crossover to bimolecular exciton decay is found. This
      suggests a spatial extent of the one-dimensional exciton of 30-50 nm, which is
      significantly smaller than the value of 92 nm for the three-dimensional exciton
      diameter in bulk PbSe. The Auger decay time increases with NR length, which is
      beneficial for applications in nanocrystal lasers as well as for generation of
      free charges in photovoltaics. 

PMID- 23968452
TI  - Giant congenital nevus associated with papillary thyroid cancer: the first case
      report.

PMID- 23968453
TI  - Highly bendable, conductive, and transparent film by an enhanced adhesion of
      silver nanowires.
AB  - Recently, silver nanowires (AgNWs) have attracted considerable interest for their
      potential application in flexible transparent conductive films (TCFs). One
      challenge for the commercialization of AgNW-based TCFs is the low conductivity
      and stability caused by the weak adhesion forces between the AgNWs and the
      substrate. Here, we report a highly bendable, conductive, and transparent AgNW
      film, which consists of an underlying poly(diallyldimethyl-ammonium chloride)
      (PDDA) and AgNW composite bottom layer and a top layer-by-layer (LbL) assembled
      graphene oxide (GO) and PDDA overcoating layer (OCL). We demonstrated that PDDA
      could increase the adhesion between the AgNW and the substrate to form a uniform
      AgNW network and could also serve to improve the stability of the GO OCL. Hence,
      a highly bendable, conductive, and transparent AgNW-PDDA-GO composite TCF on a
      poly(ethylene terephthalate) (PET) substrate with Rs ~ 10 Omega/sq and T ~ 91%
      could be made by an all-solution processable method at room temperature. In
      addition, our AgNW-PDDA-GO composite TCF is stable without degradation after
      exposure to H2S gas or sonication. 

PMID- 23968454
TI  - 2,2-Diphenyl-1-picrylhydrazyl as a screening tool for recombinant monoterpene
      biosynthesis.
AB  - BACKGROUND: Monoterpenes are a class of natural C10 compounds with a range of
      potential applications including use as fuel additives, fragrances, and chemical
      feedstocks. Biosynthesis of monoterpenes in heterologous systems is yet to reach
      commercially-viable levels, and therefore is the subject of strain engineering
      and fermentation optimization studies. Detection of monoterpenes typically relies
      on gas chromatography/mass spectrometry; this represents a significant analytical
      bottleneck which limits the potential to analyse combinatorial sets of
      conditions. To address this, we developed a high-throughput method for pre
      screening monoterpene biosynthesis. RESULTS: An optimised DPPH assay was
      developed for detecting monoterpenes from two-phase microbial cultures using
      dodecane as the extraction solvent. The assay was useful for reproducible
      qualitative ranking of monoterpene concentrations, and detected standard
      preparations of myrcene and gamma-terpinene dissolved in dodecane at
      concentrations as low as 10 and 15 MUM, respectively, and limonene as low as 200
      MUM. The assay could not be used quantitatively due to technical difficulties in
      capturing the initial reaction rate in a multi-well plate and the presence of
      minor DPPH-reactive contaminants. Initially, limonene biosynthesis in
      Saccharomyces cerevisiae was tested using two different limonene synthase enzymes
      and three medium compositions. The assay indicated that limonene biosynthesis was
      enhanced in a supplemented YP medium and that the Citrus limon limonene synthase
      (CLLS) was more effective than the Mentha spicata limonene synthase (MSLS). GC-MS
      analysis revealed that the DPPH assay had correctly identified the best limonene
      synthase (CLLS) and culture medium (supplemented YP medium). Because only traces
      of limonene were detected in SD medium, we subsequently identified medium
      components that improved limonene production and developed a defined medium based
      on these findings. The best limonene titres obtained were 1.48 +/- 0.22 mg
      limonene per L in supplemented YP medium and 0.9 +/- 0.15 mg limonene per L in a
      pH-adjusted supplemented SD medium. CONCLUSIONS: The DPPH assay is useful for
      detecting biosynthesis of limonene. Although the assay cannot be used
      quantitatively, it proved successful in ranking limonene production conditions
      qualitatively and thus is suitable as a first-tier screen. The DPPH assay will
      likely be applicable in detecting biosynthesis of several other monoterpenes and
      for screening libraries of monoterpene-producing strains.

PMID- 23968455
TI  - Simultaneous light-directed synthesis of mirror-image microarrays in a
      photochemical reaction cell with flare suppression.
AB  - The use of photolabile protecting groups is a versatile and well-established
      means of synthesizing high complexity microarrays of biopolymers, such as nucleic
      acids and peptides, for high-throughput analysis. The synthesis takes place in a
      photochemical reaction cell which positions the microarray substrate at the focus
      of the optical system delivering the light and which can be connected to a
      fluidics system which delivers appropriate reagents to the surface in synchrony
      with the light exposure. Here we describe a novel photochemical reaction cell
      which allows for the simultaneous synthesis of microarrays on two substrates. The
      reaction cell positions both substrates within the limited depth-of-focus of the
      optical system while maintaining the necessary reagent flow conditions. The
      resulting microarrays are mirror images of each other but otherwise essentially
      identical. The new reaction cell doubles the throughput of microarray synthesis
      without increasing the consumption of reagents. In addition, a secondary flow
      chamber behind the reaction cell can be filled with an absorbent and index
      matching fluid to eliminate reflections from light exiting the reaction cell
      assembly, greatly reducing unintended light exposure that reduces the sequence
      fidelity of the microarray probes. 

PMID- 23968456
TI  - Rheumatoid arthritis is associated with reduced adiposity but not with
      unfavorable major cardiovascular risk factor profiles and enhanced carotid
      atherosclerosis in black Africans from a developing population: a cross-sectional
      study.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is characterized by inflamed joint
      derived cytokine-mediated high-grade systemic inflammation that enhances
      cardiovascular metabolic risk and disease in developed populations. We
      investigated the potential impact of RA on cardiovascular risk factors including
      systemic inflammation and atherosclerosis, and their relationships in black
      Africans from a developing population. METHODS: We evaluated demographic
      features, adiposity indices, major traditional cardiovascular risk factors,
      circulating C-reactive protein and interleukin-6 concentrations and ultrasound
      determined carotid intima-media thickness (cIMT) in 274 black Africans; 115 had
      established RA. Data were analyzed in confounder-adjusted mixed regression
      models. RESULTS: The body mass index and waist-height ratio were lower in RA
      compared to non-RA subjects (29.2 (6.6) versus 33.7 (8.0), P < 0.0001 and 0.58
      (0.09) versus 0.62 (0.1), P = 0.0003, respectively). Dyslipidemia was less
      prevalent in patients with RA (odds ratio (OR) (95% confidence interval (CI) =
      0.54 (0.30 to 1.00)); this disparity was no longer significant after further
      adjustment for reduced adiposity and chloroquine use. RA was also not associated
      with hypertension, current smoking and diabetes. The number of major traditional
      risk factors did not differ by RA status (1.1 (0.8) versus 1.2 (0.9), P = 0.7).
      Circulating C-reactive protein concentrations were similar and serum interleukin
      6 concentrations reduced in RA (7.2 (3.1) versus 6.7 (3.1) mg/l, P = 0.7 and 3.9
      (1.9) versus 6.3 (1.9) pg/ml, P < 0.0001, respectively). The cIMT was 0.700
      (0.085) and 0.701 (0.111) mm in RA and non-RA subjects, respectively (P = 0.7).
      RA disease activity and severity parameters were consistently unrelated to
      systemic inflammation, despite the presence of clinically active disease in 82.6%
      of patients. In all participants, adiposity indices, smoking and converting
      angiotensin inhibitor non-use were associated with increased systemic
      inflammation, which related to more atherogenic lipid profiles, and circulating
      low density lipoprotein concentrations were associated with cIMT (partial R =
      0.153, P = 0.032); RA did not impact on these relationships (interaction P
      >=0.1). CONCLUSIONS: Among black Africans, patients with established RA
      experience reduced overall and abdominal adiposity but no enhanced major
      traditional risk factor and atherosclerosis burden. This study further suggests
      that an absent interleukin-6 release by inflamed RA joints into the circulation
      may account for this unaltered cardiovascular disease risk.

PMID- 23968457
TI  - Self-awareness of functional impairment in individuals at clinical high-risk for
      psychosis.
AB  - AIMS: A major public health concern associated with schizophrenia is the long
      term disability that involves an inability to function independently in the
      community. An individual's self-awareness of functional impairment may be a
      significant factor contributing to long-term disability. In fact, subjective
      interpretation of one's illness impacts treatment participation and adherence,
      and is linked to poor outcomes. However, it remains unclear how illness-related
      functional impairment is perceived by individuals prior to the onset of
      psychosis. This study aims to examine the relationship between clinician-based
      and self-report assessments of functioning, as well as the contribution of
      clinical symptoms to this relationship in individuals at clinical high-risk for
      psychosis. METHODS: The Sheehan Disability Scale, a self-rated instrument, was
      used to measure disruption in daily functioning in social and role functioning
      due to symptoms in a sample of 73 treatment-seeking patients at clinical high
      risk for psychosis and 50 healthy controls. RESULTS: Relative to healthy
      controls, clinical high-risk patients self-reported significant disruptions in
      social and role functioning. In addition, a specific relationship emerged in that
      clinician-rated measures of functioning and depression were related to subjective
      functioning. CONCLUSIONS: These findings suggest that clinical high-risk patients
      are significantly disturbed by their illness. Self-reported disruption of daily
      functioning was associated with clinician-rated functioning and depressive
      symptoms, further highlighting the impact of functional impairments on the level
      of distress experienced by patients in the early phases of the illness.
      Intervention strategies that repair functional impairment before the onset of
      psychosis may prevent long-term disability.

PMID- 23968458
TI  - Evaluation of two prevention programs 'Early Steps' and 'Faustlos' in daycare
      centers with children at risk: the study protocol of a cluster randomized
      controlled trial.
AB  - BACKGROUND: While early programs to prevent aggression and violence are widely
      used, only a few controlled trials of effectiveness of psychoanalytically based
      prevention programs for preschoolers have been evaluated. This study compares
      'Faustlos' (a violence prevention program) and 'Early Steps' (a
      psychoanalytically based, whole daycare center intervention to prevent violence)
      in daycare centers in socioeconomically deprived neighborhoods. METHODS/DESIGN:
      Preschoolers in 14 daycare centers in Frankfurt, Germany, participate in a
      cluster randomized controlled trial (CRCT). The daycare centers were randomly
      chosen from a representative baseline survey of all Frankfurt's daycare centers
      carried out in 2003 (n = 5,300) with the following stratifying factors:
      children's aggressiveness, hyperactivity, anxiety and socioeconomic status.
      Additionally, the geographic identification of socioeconomically deprived
      neighborhoods regarding low-income children was taken from the Frankfurt
      Municipality Statistics. Children's attachment classification and children's
      aggressiveness, hyperactivity, anxiety and social competence are measured as
      outcome criteria before and after 2 years of intervention. The programs in the
      study aim to reach a high-risk population. Therefore, the combination of a random
      sampling of daycare centers out of a representative baseline survey in all
      daycare centers in Frankfurt and the application of official data on the local
      distribution of low-income children are unique features offered by the EVA study
      design. Data on preschooler's attachment representations are collected in
      socioeconomically deprived neighborhoods for the first time. TRIAL REGISTRATION
      DRKS-ID: DRKS00003500.

PMID- 23968459
TI  - Bond cleavage during isobutanol thermal decomposition and the breaking of C-C
      bonds in alcohols at high temperatures.
AB  - Isobutanol was thermally decomposed in a single pulse shock tube under conditions
      where chain processes were suppressed. The main reaction is the breaking of C-C
      bonds. Literature rate expressions, experimentally determined, are found in some
      cases to be in disagreement. The rate expressions for the decomposition processes
      at temperatures of 1090 to 1240 K and pressures of 1.5 and 6 atm are k(isobutanol
      -> isopropyl + hydroxymethyl) + k(isobutanol -> methyl + 1-hydroxypropyl-2) =
      10(16.7+/-0.3) exp(-41097 +/- 750) s(-1), where k(isobutanol -> isopropyl +
      hydroxymethyl) = 10(16.45 +/-0.3) exp(-40910 +/- 750/T) s(-1) and k(isobutanol ->
      methyl + 1-hydroxypropyl-2) = 10(16.38+/-0.3) exp(-41560 +/- 750/T) s(-1). These
      values permit comparisons with recent estimates including those from ab initio
      calculations. A new procedure is presented that uses information on the kinetics
      of bond breaking reactions of alkanes and the effect of OH substitution to derive
      rate coefficients for similar reactions of alcohols. This leads to the following
      rate expression for the smaller alcohols, at temperatures of 1090 to 1240 K and
      pressures of 1.5 and 6 atm, k(ethanol -> methyl + hydroxymethyl) = 10(16.42+/
      0.3) exp(-43496 +/- 750 K/T) s(-1), k(isopropanol -> methyl + 1-hydroxyethyl) =
      10(16.54+/-0.3) exp(-42495 +/- 750 K/T) s(-1), k(n-propanol -> ethyl +
      hydroxymethyl) = 10(16.43+/-0.3) exp(-41696 +/- 750 K/T) s(-1), and k(n-propanol 
      > methyl + 2-hydroxymethyl) = 10(16.53+/-0.3) exp(-42945 +/- 750 K/T) s(-1).
      Extension of this approach to other alcohols is straightforward. The resulting
      correlations along with the data on dehydration of alcohols provide novel
      information of the kinetic stability of alcohols.

PMID- 23968460
TI  - Editor's Note.

PMID- 23968461
TI  - Why does the brain have so many visual areas?
AB  - Mammals vary in number of visual areas from a few to 20 or more as a result of
      new visual areas being added to the middle levels of processing hierarchies.
      Having more visual areas probably increases visual abilities, perhaps in part by
      allowing more stimulus parameters to be considered. Proposals that each visual
      area computes and thereby "detects" a specific stimulus attribute have so far
      dealt with attributes that most mammals can detect and thus do not relate to the
      issue of species differences in numbers of areas. The problem of forming and
      maintaining complex patterns of interconnections between many different sets of
      distinct processing models within an area may limit multiplying functions within
      a field. In addition, the adding of new visual areas is a way of avoiding
      constraints on modifying existing visual areas that are imposed by the ongoing
      functional requirements. Thus, increasing the number of visual or other cortical
      areas is an effective and apparently common mechanism for evolving new
      capacities. 

PMID- 23968462
TI  - Timing functions of the cerebellum.
AB  - This study investigated the effects of different types of neurological deficits
      on timing functions. The performance of Parkinson, cerebellar, cortical, and
      peripheral neuropathy patients was compared to age-matched control subjects on
      two separate measures of timing functions. The first task involved the production
      of timed intervals in which the subjects attempted to maintain a simple rhythm.
      The second task measured the subjects' perceptual ability to discriminate between
      small differences in the duration of two intervals. The primacy of the cerebellum
      in timing functions was demonstrated by the finding that these were the only
      patients who showed a deficit in both the production and perception of timing
      tasks. The cerebellar group was found to have increased variability in performing
      rhythmic tapping and they were less accurate than the other groups in making
      perceptual discriminations regarding small differences in duration. Critically,
      this perceptual deficit appears to be specific to the perception of time since
      the cerebellar patients were unaffected in a control task measuring the
      perception of loudness. It is argued that the operation of a timing mechanism can
      be conceptualized as an isolable component of the motor control system.
      Furthermore, the results suggest that the domain of the cerebellar timing process
      is not limited to the motor system, but is employed by other perceptual and
      cognitive systems when temporally predictive computations are needed. 

PMID- 23968463
TI  - Positron emission tomographic studies of the processing of singe words.
AB  - PET images of blood flow change that were averaged across individuals were used
      to identify brain areas related to lexical (single-word) processing, A small
      number of discrete areas were activated during several task conditions including:
      modality-specific (auditory or visual) areas activated by passive word input,
      primary motor and premotor areas during speech output, and yet further areas
      during tasks making semantic or intentional demands. 

PMID- 23968464
TI  - Why are "What" and "Where" Processed by Separate Cortical Visual Systems? A
      Computational Investigation.
AB  - In the primate visual system, the identification of objects and the processing of
      spatial information are accomplished by different cortical pathways. The
      computational properties of this "two-systems" design were explored by
      constructing simplifying connectionist models. The models were designed to
      simultaneously classify and locate shapes that could appear in multiple positions
      in a matrix, and the ease of forming representations of the two kinds of
      information was measured. Some networks were designed so that all hidden nodes
      projected to all output nodes, whereas others had the hidden nodes split into two
      groups, with some projecting to the output nodes that registered shape identity
      and the remainder projecting to the output nodes that registered location. The
      simulations revealed that splitting processing into separate streams for
      identifying and locating a shape led to better performance only under some
      circumstances. Provided that enough computational resources were available in
      both streams, split networks were able to develop more efficient internal
      representations, as revealed by detailed analyses of the patterns of weights
      between connections. 

PMID- 23968465
TI  - The recognition of antonymy by a language-enriched right hemisphere.
AB  - A commissurotomy patient with limited language in the right hemisphere was tested
      for ability to recognize direct and indirect antonyms. Normal subjects performing
      this task recognize direct antonyms faster than indirect. The patient's left
      hemisphere responded normally, but his right showed no difference in response to
      direct and indirect antonyms. It is concluded that the patient's right hemisphere
      had not learned that particular pairs of adjectives (the direct antonyms) can be
      used to represent the attribute whose contrasting values they express. Such
      learning normally occurs in the course of reasoning about attributes of things
      and events, but presumably failed to occur in this patient's right hemisphere
      because its powers of reasoning are severely limited. 

PMID- 23968466
TI  - Regulation of synaptic molecular architecture in a rat sympathetic ganglion and
      hippocampus.
AB  - Extensive evidence suggests that the synapse, the communicative organelle between
      neurons, plays a pivotal role in learning and memory. To begin defining
      epigenetic factors that potentially regulate molecular structure of the synapse,
      we have been studying a relatively simple model system, the rat sympathetic,
      superior cervical ganglion. Initially, we focused on the postsynaptic density
      (PSD), a disc-shaped structure in the postsynaptic neuron (see cover
      illustration). Previously, we found that trans-synaptic impulse activity
      regulates the predominant PSD protein molecule (PSDp). We now examine two related
      questions. Do other factors influence c synaptic structure independent of
      presynaptic innervation? Conversely, does denervation alter synaptic molecular
      structure in the hippocampus, as in the ganglion? Our studies indicate that the
      trophic protein, nerve growth factor, that governs sympathetic development and
      mature function, regulates the PSDp in normal and denervated ganglia.
      Consequently, synaptic structure in the periphery is, indeed, regulated by
      multiple factors. In the brain, fimbria-fornix lesions, which partially denervate
      the hippocampus, significantly reduce the hippocampal PSDp. We conclude that
      presynaptic innervation regulates synaptic structure in the hippocampus, as well
      as the periphery. More generally, epigenetic factors apparently regulate synaptic
      structure, potentially providing a molecular mechanism for information storage at
      the synapse. 

PMID- 23968467
TI  - Discriminating lysosomal membrane protein types using dynamic neural network.
AB  - This work presents a dynamic artificial neural network methodology, which
      classifies the proteins into their classes from their sequences alone: the
      lysosomal membrane protein classes and the various other membranes protein
      classes. In this paper, neural networks-based lysosomal-associated membrane
      protein type prediction system is proposed. Different protein sequence
      representations are fused to extract the features of a protein sequence, which
      includes seven feature sets; amino acid (AA) composition, sequence length,
      hydrophobic group, electronic group, sum of hydrophobicity, R-group, and
      dipeptide composition. To reduce the dimensionality of the large feature vector,
      we applied the principal component analysis. The probabilistic neural network,
      generalized regression neural network, and Elman regression neural network (RNN)
      are used as classifiers and compared with layer recurrent network (LRN), a
      dynamic network. The dynamic networks have memory, i.e. its output depends not
      only on the input but the previous outputs also. Thus, the accuracy of LRN
      classifier among all other artificial neural networks comes out to be the
      highest. The overall accuracy of jackknife cross-validation is 93.2% for the data
      set. These predicted results suggest that the method can be effectively applied
      to discriminate lysosomal associated membrane proteins from other membrane
      proteins (Type-I, Outer membrane proteins, GPI-Anchored) and Globular proteins,
      and it also indicates that the protein sequence representation can better reflect
      the core feature of membrane proteins than the classical AA composition.

PMID- 23968485
TI  - Design, synthesis, and characterization of novel tetrahydropyran-based bacterial
      topoisomerase inhibitors with potent anti-gram-positive activity.
AB  - There is an urgent need for new antibacterial drugs that are effective against
      infections caused by multidrug-resistant pathogens. Novel nonfluoroquinolone
      inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV)
      have the potential to become such drugs because they display potent antibacterial
      activity and exhibit no target-mediated cross-resistance with fluoroquinolones.
      Bacterial topoisomerase inhibitors that are built on a tetrahydropyran ring
      linked to a bicyclic aromatic moiety through a syn-diol linker show potent anti
      Gram-positive activity, covering isolates with clinically relevant resistance
      phenotypes. For instance, analog 49c was found to be a dual DNA gyrase
      topoisomerase IV inhibitor, with broad antibacterial activity and low propensity
      for spontaneous resistance development, but suffered from high hERG K(+) channel
      block. On the other hand, analog 49e displayed lower hERG K(+) channel block
      while retaining potent in vitro antibacterial activity and acceptable frequency
      for resistance development. Furthermore, analog 49e showed moderate clearance in
      rat and promising in vivo efficacy against Staphylococcus aureus in a murine
      infection model. 

PMID- 23968486
TI  - Bioaccumulation of perfluoroalkyl substances by Daphnia magna in water with
      different types and concentrations of protein.
AB  - Perfluoroalkyl substances (PFASs) are sometimes regarded as proteinophilic
      compounds, however, there is no research report about the effect of environmental
      protein on the bioaccumulation of PFASs in waters. In the present study we
      investigated influences of protein on the bioaccumulation of six kinds of PFASs
      by Daphnia magna in water; it included perfluorooctane sulfonate,
      perfluorooctanoic acid, perfluorononanoic acid, perfluorodecanoic acid,
      perfluoroundecanoic acid, and perfluorododecanoic acid. Two types of protein
      including bovine albumin from animal and soy peptone from plant were compared and
      the effects of protein concentration were investigated. Both types of protein at
      high concentrations (10 and 20 mg L(-1)) suppressed the bioaccumulation of PFASs.
      When protein concentration increased from 0 to 20 mg L(-1), the decreasing ratios
      of the PFAS body burden (35.3-52.9%) in Daphnia magna induced by bovine albumin
      were significantly higher than those (22.0-36.6%) by soy peptone. The dialysis
      bag experiment results showed that the binding of PFASs to protein followed the
      Freundlich isotherm, suggesting it is not a linear partitioning process but an
      adsorption-like process. The partition coefficients of PFASs between bovine
      albumin and water were higher compared to soy peptone; this resulted in higher
      reducing rates of freely dissolved concentrations of PFASs with increasing bovine
      albumin concentration, leading to a stronger suppression of PFAS bioaccumulation.
      However, the presence of both types of protein with a low concentration (1 mg L(
      1)) enhanced the bioaccumulation of PFASs. Furthermore, the water-based
      bioaccumulation factor based on the freely dissolved concentrations of PFASs even
      increased with and the depuration rate constants of PFASs from Daphnia magna
      decreased with protein concentration, suggesting that protein would not only
      reduce the bioavailable concentrations and uptake rates of PFASs but also lower
      the elimination rates of PFASs in Daphnia magna. Because these two opposite
      effects would change with different protein concentrations in water, the net
      effect of protein on PFAS bioaccumulation would also vary with protein
      concentration. 

PMID- 23968487
TI  - Prevalence of genital Chlamydia trachomatis infection among young men and women
      in Spain.
AB  - BACKGROUND: There are no accurate data regarding the real prevalence of Chlamydia
      trachomatis infection in Spain. Our aim was to determine the prevalence of C.
      trachomatis infections and the risk factors for acquiring them among 1,048 young
      (15-24 years old) inhabitants of Laviana. METHODS: The study was completed in the
      period between 1st November 2010 and 31st December 2011. We conducted a capture
      strategy in the whole population, instead of only in a sample group, with a
      capture conducted in schools, in the local health centre, by post and by phone as
      a last resort. The design was based on the model used by Shafer to increase
      screening rates. C. trachomatis was identified by RT-PCR in urine samples.
      RESULTS: A total of 487 sexually active people underwent the test, which implies
      a response rate of 59.8% of the sexually active people (target population). The
      prevalence was 4.1% (CI 95%: 3.1-5.8): women: 4% ( CI 95%; 2.8-6.4) and men: 4.3%
      (CI 95%: 2.9-7.2). The circulating genotype was the E genotype. There was an
      increase in the risk of C. trachomatis infection when barrier contraceptives were
      not routinely used OR: 4.76 (CI 95%:1.30-17.36) p<0.05. CONCLUSIONS: In our study
      the prevalence in women resembles those found in other countries in Europe and
      the prevalence in men is similar to that in women. Screening for C. trachomatis
      infection in women would be cost-effective in Spain given the prevalence of C.
      trachomatis measured by this study. The use of a condom is the best preventative
      measure for avoiding STIs in sexually active people.

PMID- 23968489
TI  - Experimental and computational studies on the [3,3]- and [3,5]-sigmatropic
      rearrangements of acetoxycyclohexadienones: a non-ionic mechanism for acyl
      migration.
AB  - Flash vacuum pyrolysis studies of substituted 6-acetoxy-2,4-cyclohexadienones (3
      and 10) from 300 to 500  degrees C provide strong experimental evidence that
      direct [3,5]-sigmatropic rearrangements in these molecules are favored over the
      more familiar [3,3]-sigmatropic rearrangements. The preference holds when the
      results are extrapolated to 0.0% conversion, indicating that this is a concerted
      process. Pyrolysis of 6,6-diacetoxy-2-methyl-2,4-cyclohexadienone (9) at 350 
      degrees C gives a modest yield of the initial [3,5]-sigmatropic rearrangement
      product, 2,6-diacetoxy-6-methyl-2,4-cyclohexadienone (11). Qualitative arguments
      and electronic structure theory calculations are in agreement that the lowest
      energy pathway for each [3,5]-sigmatropic rearrangement is via an allowed,
      concerted pseudopericyclic transition state. The crystal structures of compounds
      3, 9, and 10 prefigure these transition states. The selectivity for the [3,5]
      products increases with an increasing temperature. This unexpected selectivity is
      explained by a concerted, intramolecular, and pseudopericyclic transition state
      (TS-5) that forms a tetrahedral interemediate (ortho-acid ester 4'), followed by
      similar ring openings to isomeric phenols, which shifts the equilibrium toward
      the phenols from the [3,5] (but not the [3,3]) products. 

PMID- 23968488
TI  - Detecting association of rare variants by testing an optimally weighted
      combination of variants for quantitative traits in general families.
AB  - Although next-generation sequencing technology allows sequencing the whole genome
      of large groups of individuals, the development of powerful statistical methods
      for rare variant association studies is still underway. Even though many
      statistical methods have been developed for mapping rare variants, most of these
      methods are for unrelated individuals only, whereas family data have been shown
      to improve power to detect rare variants. The majority of the existing methods
      for unrelated individuals is essentially testing the effect of a weighted
      combination of variants with different weighting schemes. The performance of
      these methods depends on the weights being used. Recently, researchers proposed a
      test for Testing the effect of an Optimally Weighted combination of variants
      (TOW) for unrelated individuals. In this article, we extend our previously
      developed TOW for unrelated individuals to family-based data and propose a novel
      test for Testing the effect of an Optimally Weighted combination of variants for
      Family-based designs (TOW-F). The optimal weights are analytically derived. The
      results of extensive simulation studies show that TOW-F is robust to population
      stratification in a wide range of population structures, is robust to the
      direction and magnitude of the effects of causal variants, and is relatively
      robust to the percentage of neutral variants. 

PMID- 23968490
TI  - Spectral modifications and polarization dependent coupling in tailored assemblies
      of quantum dots and plasmonic nanowires.
AB  - The coupling of optical emitters with a nanostructured environment is at the
      heart of nano- and quantum optics. We control this coupling by the lithographic
      positioning of a few (1-3) quantum dots (QDs) along plasmonic silver nanowires
      with nanoscale resolution. The fluorescence emission from the QD-nanowire systems
      is probed spectroscopically, by microscopic imaging and decay time measurements.
      We find that the plasmonic modes can strongly modulate the fluorescence emission.
      For a given QD position, the local plasmon field dictates the coupling
      efficiency, and thus the relative weight of free space radiation and emission
      into plasmon modes. Simulations performed with a generic few-level model give
      very good agreement with experiment. Our data imply that the 2D degenerate
      emission dipole orientation of the QD can be forced to predominantly emit to one
      polarization component dictated by the nanowire modes. 

PMID- 23968491
TI  - Programmable interactions of functionalized single bioparticles in a
      dielectrophoresis-based microarray chip.
AB  - Manipulating single biological objects is a major unmet challenge of biomedicine.
      Herein, we describe a lab-on-a-chip platform based on dielectrophoresis (DEP).
      The DEParray is a prototypal version consisting of 320 * 320 arrayed electrodes
      generating >10,000 spherical DEP cages. It allows the capture and software-guided
      movement to predetermined spatial coordinates of single biological objects. With
      the DEParray we demonstrate (a) forced interaction between a single, preselected
      target cell and a programmable number of either microspheres or natural killer
      (NK) cells, (b) on-chip immunophenotypic discrimination of individual cells based
      on differential rosetting with microspheres functionalized with monoclonal
      antibodies to an inhibitory NK cell ligand (HLA-G), (c) on-chip, real-time (few
      minutes) assessment of immune lysis by either visual inspection or semiautomated,
      time-lapse reading of a fluorescent dye released from NK cell-sensitive targets,
      and (d) manipulation and immunophenotyping with limiting amounts (about 500)
      cells. To our knowledge, this is the first report describing a DEP-based lab-on-a
      chip platform for the quick, arrayed, software-guided binding of individually
      moved biological objects, the targeting of single cells with microspheres, and
      the real-time characterization of immunophenotypes. The DEParray candidates as a
      discovery tool for novel cell:cell interactions with no prior (immuno)phenotypic
      knowledge.

PMID- 23968492
TI  - Community engagement with genetics: public perceptions and expectations about
      genetics research.
AB  - BACKGROUND: Knowledge of molecular biology and genomics continues to expand
      rapidly, promising numerous opportunities for improving health. However, a key
      aspect of the success of genomic medicine is related to public understanding and
      acceptance. DESIGN: Using community consultations and an online survey, we
      explored public attitudes and expectations about genomics research. RESULTS:
      Thirty-three members of the general public in Newfoundland, Canada, took part in
      the community sessions, while 1024 Atlantic Canadians completed the online
      survey. Overall, many participants noted they lacked knowledge about genetics and
      associated research and took the opportunity to ask numerous questions throughout
      sessions. Participants were largely hopeful about genomics research in its
      capacity to improve health, not only for current residents, but also for future
      generations. However, they did not accept such research uncritically, and a
      variety of complex issues and questions arose during the community consultations
      and were reflected in survey responses. DISCUSSION: With the proliferation of
      biobanks and the rapid pace of discoveries in genomics research, public support
      will be crucial to realize health improvements. If researchers can engage the
      public in regular, transparent dialogue, this two-way communication could allow
      greater understanding of the research process and the design of efficient and
      effective genetic health services, informed by the public that will use them.

PMID- 23968493
TI  - Clinical, histopathologic, and immunofluorescence findings in levamisole/cocaine
      induced thrombotic vasculitis.

PMID- 23968494
TI  - Quantifying the mosquito's sweet tooth: modelling the effectiveness of attractive
      toxic sugar baits (ATSB) for malaria vector control.
AB  - BACKGROUND: Current vector control strategies focus largely on indoor measures,
      such as long-lasting insecticide treated nets (LLINs) and indoor residual
      spraying (IRS); however mosquitoes frequently feed on sugar sources outdoors,
      inviting the possibility of novel control strategies. Attractive toxic sugar
      baits (ATSB), either sprayed on vegetation or provided in outdoor bait stations,
      have been shown to significantly reduce mosquito densities in these settings.
      METHODS: Simple models of mosquito sugar-feeding behaviour were fitted to data
      from an ATSB field trial in Mali and used to estimate sugar-feeding rates and the
      potential of ATSB to control mosquito populations. The model and fitted
      parameters were then incorporated into a larger integrated vector management
      (IVM) model to assess the potential contribution of ATSB to future IVM
      programmes. RESULTS: In the Mali experimental setting, the model suggests that
      about half of female mosquitoes fed on ATSB solution per day, dying within
      several hours of ingesting the toxin. Using a model incorporating the number of
      gonotrophic cycles completed by female mosquitoes, a higher sugar-feeding rate
      was estimated for younger mosquitoes than for older mosquitoes. Extending this
      model to incorporate other vector control interventions suggests that an IVM
      programme based on both ATSB and LLINs may substantially reduce mosquito density
      and survival rates in this setting, thereby substantially reducing parasite
      transmission. This is predicted to exceed the impact of LLINs in combination with
      IRS provided ATSB feeding rates are 50% or more of Mali experimental levels. In
      addition, ATSB is predicted to be particularly effective against Anopheles
      arabiensis, which is relatively exophilic and therefore less affected by IRS and
      LLINs. CONCLUSIONS: These results suggest that high coverage with a combination
      of LLINs and ATSB could result in substantial reductions in malaria transmission
      in this setting. Further field studies of ATSB in other settings are needed to
      assess the potential of ATSB as a component in future IVM malaria control
      strategies.

PMID- 23968496
TI  - Clinical associations of serum interleukin-17 in systemic lupus erythematosus.
AB  - INTRODUCTION: Serum interleukin (IL)-17 concentrations have been reported to be
      increased in systemic lupus erythematosus (SLE), but associations with clinical
      characteristics are not well understood. We characterized clinical associations
      of serum IL-17 in SLE. METHODS: We quantified IL-17 in serum samples from 98 SLE
      patients studied cross-sectionally, and in 246 samples from 75 of these patients
      followed longitudinally over two years. Disease activity was recorded using the
      SLE Disease Activity Index (SLEDAI)-2k. Serum IL-6, migration inhibitory factor
      (MIF), and B cell activating factor of the tumour necrosis factor family (BAFF)
      were also measured in these samples. RESULTS: Serum IL-17 levels were
      significantly higher in SLE patients compared to healthy donors (P <0.0001). No
      correlation was observed between serum IL-17 and SLEDAI-2k, at baseline or during
      longitudinal follow-up. However, we observed that SLEDAI-2k was positively
      correlated with IL-17/IL-6 ratio. Serum IL-17 was significantly increased in SLE
      patients with central nervous system (CNS) disease (P = 0.0298). A strong
      correlation was observed between serum IL-17 and IL-6 (r = 0.62, P <0.0001), and
      this relationship was observed regardless of disease activity and persisted when
      integrating cytokine levels over the period observed (r = 0.66, P <0.0001). A
      strong correlation of serum IL-17 was also observed with serum BAFF (r = 0.64, P
      <0.0001), and MIF (r = 0.36, P = 0.0016). CONCLUSIONS: Serum IL-17 concentration
      correlates poorly with SLE disease activity but is significantly elevated in
      patients with CNS disease. IL-17/IL-6 ratio may be more useful than IL-17 or IL-6
      alone to characterize Th17-driven disease, such as SLE. The association of other
      cytokines with serum IL-17 suggests that IL-17 may drive activation of diverse
      immune pathways in SLE.

PMID- 23968497
TI  - Separation of Escherichia coli bacteria from peripheral blood mononuclear cells
      using standing surface acoustic waves.
AB  - A microfluidic device was developed to separate heterogeneous particle or cell
      mixtures in a continuous flow using acoustophoresis. In this device, two
      identical surface acoustic waves (SAWs) generated by interdigital transducers
      (IDTs) propagated toward a microchannel, which accordingly built up a standing
      surface acoustic wave (SSAW) field across the channel. A numerical model,
      coupling a piezoelectric effect in the solid substrate and acoustic pressure in
      the fluid, was developed to provide a better understanding of SSAW-based particle
      manipulation. It was found that the pressure nodes across the channel were
      individual planes perpendicular to the solid substrate. In the separation
      experiments, two side sheath flows hydrodynamically focused the injected particle
      or cell mixtures into a very narrow stream along the centerline. Particles
      flowing through the SSAW field experienced an acoustic radiation force that
      highly depends on the particle properties. As a result, dissimilar particles or
      cells were laterally attracted toward the pressure nodes at different magnitudes,
      and were eventually switched to different outlets. Two types of fluorescent
      microspheres with different sizes were successfully separated using the developed
      device. In addition, Escherichia coli bacteria premixed in peripheral blood
      mononuclear cells (PBMCs) were also efficiently isolated using the SSAW-base
      separation technique. Flow cytometric analysis on the collected samples found
      that the purity of separated E. coli bacteria was 95.65%. 

PMID- 23968498
TI  - Comparing single-site with multisite rTMS for the treatment of chronic tinnitus -
      clinical effects and neuroscientific insights: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Several years ago, repetitive transcranial magnetic stimulation
      (rTMS) of the auditory cortex has been introduced as a treatment approach for
      chronic tinnitus. Even if this treatment is beneficial for a subgroup of
      patients, the overall effects are limited. This limitation may be due to the fact
      that the auditory cortex is only one of several brain areas involved in tinnitus.
      Whereas auditory areas are considered to code for tinnitus loudness, conscious
      perception of and attention allocation to tinnitus is supposed to be reflected by
      network activity involving frontal and parietal cortical areas. The aim of the
      present study is to influence this frontoparietal network more efficiently by
      perturbing the most important nodes with rTMS. METHODS/DESIGN: This is a
      randomized, double-blind, parallel-group study. Patients receive rTMS treatment
      on 10 consecutive working days using either the multisite rTMS protocol (left
      dorsolateral prefrontal, 1,000 stimuli, 20 Hz; left temporoparietal, 1,000
      stimuli, 1 Hz; right temporoparietal stimulation, 1,000 stimuli, 1 Hz) or a
      single-site protocol (unilateral stimulation of the temporoparietal cortex, 3,000
      stimuli, 1 Hz). Individuals aged 18 to 70 years with chronic tinnitus >=6-month
      duration and a Tinnitus Handicap Inventory score >=38 are recruited for the
      study. A total of 50 patients are needed to detect a clinical relevant change of
      tinnitus severity (alpha = 0.05; 1 - beta = 0.80). Primary outcome measures are
      the change in the Tinnitus Questionnaire score from baseline to the end of
      treatment as well as the number of treatment responders as defined by a reduction
      in the Tinnitus Questionnaire score of >=5 points. Furthermore, changes in brain
      structure and activity are assessed using (functional) magnetic resonance imaging
      and electroencephalography in the resting state. Those measurements are also
      performed in 25 healthy control subjects. DISCUSSION: This study is designed to
      reveal whether network stimulation is superior to single-site stimulation in the
      treatment of chronic tinnitus. Furthermore, the comparison between tinnitus
      patients and healthy controls and the longitudinal effects of both rTMS treatment
      protocols on brain structure and function allow inferences to be made about the
      neural correlates of tinnitus. TRIAL REGISTRATION: Clinical Trials: NCT01663324.

PMID- 23968500
TI  - Potential role of oral anticoagulants in the treatment of patients with coronary
      artery disease: focus on dabigatran.
AB  - The pharmacologic management of patients with high-risk coronary artery disease
      consists of aspirin and a P2Y12 receptor inhibitor. Chronic oral anticoagulation
      with warfarin is the major treatment strategy to attenuate thromboembolism or
      stroke in patients with deep vein thrombosis, pulmonary embolism, heart failure
      and atrial fibrillation. A substantial percentage of the latter group of patients
      have coronary artery disease and may require stenting with long-term dual
      antiplatelet therapy in addition to therapy with warfarin to reduce arterial
      ischemic events in addition to stroke. These new oral anticoagulants have been
      developed for long-term therapy to overcome the limitations of warfarin.
      Dabigatran is a direct thrombin inhibitor and its role in patients with acute
      coronary syndrome is being explored. 

PMID- 23968499
TI  - Gene expression responses to mechanical stimulation of mesenchymal stem cells
      seeded on calcium phosphate cement.
AB  - INTRODUCTION: The aim of the study reported here was to investigate the molecular
      responses of human mesenchymal stem cells (MSC) to loading with a model that
      attempts to closely mimic the physiological mechanical loading of bone, using
      monetite calcium phosphate (CaP) scaffolds to mimic the biomechanical properties
      of bone and a bioreactor to induce appropriate load and strain. METHODS: Human
      MSCs were seeded onto CaP scaffolds and subjected to a pulsating compressive
      force of 5.5+/-4.5 N at a frequency of 0.1 Hz. Early molecular responses to
      mechanical loading were assessed by microarray and quantitative reverse
      transcription-polymerase chain reaction and activation of signal transduction
      cascades was evaluated by western blotting analysis. RESULTS: The maximum
      mechanical strain on cell/scaffolds was calculated at around 0.4%. After 2 h of
      loading, a total of 100 genes were differentially expressed. The largest cluster
      of genes activated with 2 h stimulation was the regulator of transcription, and
      it included FOSB. There were also changes in genes involved in cell cycle and
      regulation of protein kinase cascades. When cells were rested for 6 h after
      mechanical stimulation, gene expression returned to normal. Further resting for a
      total of 22 h induced upregulation of 63 totally distinct genes that were mainly
      involved in cell surface receptor signal transduction and regulation of metabolic
      and cell division processes. In addition, the osteogenic transcription factor
      RUNX-2 was upregulated. Twenty-four hours of persistent loading also markedly
      induced osterix expression. Mechanical loading resulted in upregulation of Erk1/2
      phosphorylation and the gene expression study identified a number of possible
      genes (SPRY2, RIPK1, SPRED2, SERTAD1, TRIB1, and RAPGEF2) that may regulate this
      process. CONCLUSION: The results suggest that mechanical loading activates a
      small number of immediate-early response genes that are mainly associated with
      transcriptional regulation, which subsequently results in activation of a wider
      group of genes including those associated with osteoblast proliferation and
      differentiation. The results provide a valuable insight into molecular events and
      signal transduction pathways involved in the regulation of MSC osteogenic
      differentiation in response to a physiological level of mechanical stimulation.

PMID- 23968501
TI  - Inhibiting aberrant signal transducer and activator of transcription protein
      activation with tetrapodal, small molecule Src homology 2 domain binders:
      promising agents against multiple myeloma.
AB  - The signal transducer and activator of transcription (STAT) proteins represent a
      family of cytoplasmic transcription factors that regulate a pleiotropic range of
      biological processes. In particular, Stat3 protein has attracted attention as it
      regulates the expression of genes involved in a variety of malignant processes,
      including proliferation, survival, migration, and drug resistance. Multiple
      myeloma (MM) is an incurable hematologic malignancy that often exhibits
      abnormally high levels of Stat3 activity. Although current treatment strategies
      can improve the clinical management of MM, it remains uniformly incurable with a
      dismal median survival time post-treatment of 3-4 years. Thus, novel targeted
      therapeutics are critically needed to improve MM patient outcomes. We herein
      report the development of a series of small molecule Stat3 inhibitors with potent
      anti-MM activity in vitro. These compounds showed high-affinity binding to
      Stat3's SH2 domain, inhibited intracellular Stat3 phosphorylation, and induced
      apoptosis in MM cell lines at low micromolar concentrations. 

PMID- 23968503
TI  - Aqueous solvation of Hg(OH)2: energetic and dynamical density functional theory
      studies of the Hg(OH)2-(H2O)n (n = 1-24) structures.
AB  - A systematic study of the hydration of Hg(OH)2 by the stepwise solvation approach
      is reported. The optimized structures, solvation energies, and incremental free
      energies of 1-24 water molecules interacting with the solute have been computed
      at the B3PW91 level using 6-31G(d,p) basis sets for the O and H atoms. The
      mercury atom was treated with the Stuttgart-Koln relativistic core potential in
      combination with an extended optimized valence basis set. One to three direct Hg
      water interactions appear along the solvation process. The first solvation shell
      is fully formed with 24 water molecules. A stable pentacoordinated Hg trigonal
      bipyramid structure appears for n > 15. Density functional theory (DFT) Born
      Oppenheimer molecular dynamics simulations showed the thermal stability of the
      Hg(OH)2-(H2O)24 structure at room temperature and the persistence of the trigonal
      bipyramid coordination around Hg. The Gibbs free energy for the first solvation
      shell is significantly larger for the fully solvated Hg(OH)2 than the one
      previously obtained for the HgCl2 case, due to sigma-acceptor and pi-donor
      properties involving the hydroxyl groups of the solute. This suggests that the
      transmembrane passage of Hg(OH)2 into the cell via simple diffusion is less
      favorable compared to the case when the metal is coordinated with two Cl groups. 

PMID- 23968502
TI  - Imbalance of different types of CD4(+) forkhead box protein 3 (FoxP3)(+) T cells
      in patients with new-onset systemic lupus erythematosus.
AB  - The aim of this study was to examine the numbers of CD4(+) CD25(-) forkhead box
      protein 3 (FoxP3)(+) , CD4(+) CD25(+) FoxP3(+) and CD4(+) CXCR5(+) FoxP3(+) T
      cells in patients with new-onset systemic lupus erythematosus (SLE). The numbers
      of CD4(+) CD25(-) FoxP3(+) , CD4(+) CD25(+) FoxP3(+) and CD4(+) CXCR5(+) FoxP3(+)
      T cells and the concentrations of serum interleukin (IL)-10 in 23 patients and 20
      healthy controls (HC) were measured. The potential correlations between CD4(+)
      FoxP3(+) T cells, serum IL-10 and clinical measures in SLE patients were
      analysed. In comparison with that in the HC, significantly reduced numbers of
      CD4(+) CD25(+) FoxP3(+) and CD4(+) CXCR5(+) FoxP3(+) T cells, but increased
      numbers of CD4(+) CD25(-) FoxP3(+) T cells, were detected, accompanied by
      significantly lower levels of serum IL-10 in the patients. Stratification
      analysis indicated the numbers of CD4(+) CD25(+) FoxP3(+) and CD4(+) CXCR5(+)
      FoxP3(+) T cells and serum IL-10 levels in the patients with seropositive anti
      dsDNA were significantly less than that in those with seronegative anti-dsDNA.
      Treatment with the anti-SLE therapy, particularly with prednisone, leflunomide
      and methotrexate, significantly improved the imbalance of these types of FoxP3(+)
      T cells and increased the concentrations of serum IL-10 in the drug-responding
      patients. The numbers of CD4(+) CD25(+) FoxP3(+) T cells were correlated
      negatively with the values of SLE disease activity index (SLEDAI), whereas the
      numbers of CD4(+) CD25(-) FoxP3(+) T cells were correlated positively with the
      values of SLEDAI, erythrocyte sedimentation rate (ESR) and serum C3. In addition,
      the concentrations of serum IL-10 were correlated positively with the numbers of
      CD4(+) CD25(+) FoxP3(+) T cells, but negatively with the values of SLEDAI, serum
      C3, CRP and ESR in these patients. Our data indicate that the imbalance of
      different types of FoxP3(+) CD4(+) T cells may contribute to the development of
      SLE in Chinese patients. 

PMID- 23968504
TI  - Mechanistic studies on the Pd-catalyzed vinylation of aryl halides with
      vinylalkoxysilanes in water: the effect of the solvent and NaOH promoter.
AB  - The mechanism of the Pd-catalyzed vinylation of aryl halides with
      vinylalkoxysilanes in water has been studied using different catalytic
      precursors. The NaOH promoter converts the initial vinylalkoxysilane into a
      highly reactive water-soluble vinylsilanolate species. Similarly, deuterium
      labeling experiments have shown that, irrespective of the catalytic precursor
      used, vinylation occurs exclusively at the CH vinylic functionality via a Heck
      reaction and not at the C-Si bond via a Hiyama cross-coupling. The involvement of
      a Heck mechanism is interpreted in terms of the reduced nucleophilicity of the
      base in water, which disfavors the transmetalation step. The Heck product (beta
      silylvinylarene) undergoes partial desilylation, with formation of a vinylarene,
      by three different routes: (a) hydrolytic desilylation by the aqueous solvent
      (only at high temperature); (b) transmetalation of the silyl olefin on the PdH
      Heck intermediate followed by reductive elimination of vinylarene; (c)
      reinsertion of the silyl olefin into the PdH bond of the Heck intermediate
      followed by beta-Si syn-elimination. Both the Hiyama and Heck catalytic cycles
      and desilylation mechanisms b and c have been computationally evaluated for the
      [Pd(en)Cl2] precursor in water as solvent. The calculated Gibbs energy barriers
      support the reinsertion route proposed on the basis of the experimental results. 

PMID- 23968505
TI  - Dream Bizarreness as the Cognitive Correlate of Altered Neuronal Behavior in REM
      Sleep.
AB  - Bizarreness is a cognitive feature common to REM sleep dreams, which can be
      easily measured. Because bizarreness is highly specific to dreaming, we propose
      that it is most likely brought about by changes in neuronal activity that are
      specific to REM sleep. At the level of the dream plot, bizarreness can be defined
      as either discontinuity or incongruity. In addition, the dreamer's thoughts about
      the plot may be logically deficient. We propose that dream bizarreness is the
      cognitive concomitant of two kinds of changes in neuronal dynamics during REM
      sleep. One is the disinhibition of forebrain networks caused by the withdrawal of
      the modulatory influences of norepinephrine (NE) and serotonin (5HT) in REM
      sleep, secondary to cessation of firing of locus coeruleus and dorsal raphe
      neurons. This aminergic demodulation can be mathematically modeled as a shift
      toward increased error at the outputs from neural networks, and these errors
      might be represented cognitively as incongruities and/or discontinuities. We also
      consider the possibility that discontinuities are the cognitive concomitant of
      sudden bifurcations or "jumps" in the responses of forebrain neuronal networks.
      These bifurcations are caused by phasic discharge of pontogeniculooccipital (PGO)
      neurons during REM sleep, providing a source of cholinergic modulation to the
      forebrain which could evoke unpredictable network responses. When phasic PGO
      activity stops, the resultant activity in the brain may be wholly unrelated to
      patterns of activity dominant before such phasic stimulation began.
      Mathematically such sudden shifts from one pattern of activity to a second,
      unrelated one is called a bifurcation. We propose that the neuronal bifurcations
      brought about by PGO activity might be represented cognitively as bizarre
      discontinuities of dream plot. We regard these proposals as preliminary attempts
      to model the relationship between dream cognition and REM sleep neurophysiology.
      This neurophysiological model of dream bizarreness may also prove useful in
      understanding the contributions of REM sleep to the developmental and
      experiential plasticity of the cerebral cortex. 

PMID- 23968506
TI  - Neural processes involved in directing attention.
AB  - Neural processes associated with two aspects of visual-spatial attention were
      investigated with event-related potential (ERPs): those that direct spatial
      attention to a given point in space and those that modulate the processing of
      sensory input after attention has been directed. The subjects were 6- to 9-year
      old children (51 boys and 35 girls). An arrow cue directed attention from the
      central to peripheral visual field; targets were then flashed in the attended or
      ignored visual field 600 msec after the cue. The directing of attention to the
      left vs. right visual field was associated with hemispheric differences in slow
      potentials prior to the presentation of the targets. The earliest potential,
      which started about 200 msec after the cue and was negative over the hemisphere
      contralateral to the direction of attention, was greatest over the parietal area
      and appeared to reflect processes directing attention per se. The last potential,
      which peaked 60 msec after the target and was positive over the hemisphere
      contralateral to the direction of attention, was greatest over the occipital
      parietal region. It appeared to reflect the modulation of cortical excitability
      in the regions receiving input from the relevant and irrelevant visual fields.
      The effects of spatial attention on P1, N1, and P3 ERP components following the
      targets replicated previous results. Boys appeared more aroused (as indicated by
      CNVs) and reflected faster and greater selective processing (as indicated by
      reaction time, and N1-P1 latency and amplitude) than girls. 

PMID- 23968507
TI  - Indelibility of subcortical emotional memories.
AB  - Acquisition and extinction of fear responses conditioned to a visual stimulus
      were examined in rats with ablations of visual cortex. Visual cortex lesions did
      not interfere with acquisition, indicating that visual fear conditioning, like
      auditory fear conditioning, is mediated by sub-cortical, probably thalamo
      amygdala, sensory pathways. In contrast to acquisition, extinction was greatly
      prolonged, if not prevented, by cortical ablation. This resistance to extinction
      of sub cortical emotional memories may explain certain aspects of emotional
      memory in man. 

PMID- 23968508
TI  - A simple model of prefrontal cortex function in delayed-response tasks.
AB  - Both psychologists and neurobiologists have used delayed response (DR), AB, and
      delayed matching-to-sample (DMS) tasks as tools to study the functions of
      prefrontal cortex in primates and humans. We describe a simulation model that
      relates behavioral and electrophysiological-data relevant to these tasks into a
      minimal neural network. The inputs to the network are two visual objects and a
      positive or negative reinforcement signal. As the output, the network orients
      toward one of the two objects. We subdivide the architecture of the network into
      two levels, both of which embody constraints from neuroanatomy in a simplified
      form. Level 1 consists of a sensory-motor loop with modifiable synaptic weights
      and provides a capacity for grasping. Level 2 contains memory and rule-coding
      units and modulates the lower level 1. When level 1 only is simulated, the
      network fails to learn the tasks. The errors made by the network resemble those
      of young monkeys, infants, or adults with prefrontal lesions. In particular, the
      systematic AB error can be reproduced. With level 2 on top of level 1, the
      network acquires systematic rules of behavior by mere reinforcement and rapidly
      adapts to changes in the reinforcement schedule. Learning takes place by
      selection among a repertoire of possible rules. The properties of the model are
      discussed in terms of actual behavioral and physiological data, and several
      critical experimental predictions are presented. In particular, we address the
      issues of prefrontal functions, "systematicity" in neural networks, and "mental
      Darwinism." 

PMID- 23968509
TI  - Temporal Constraints on Language Processing: Syntactic Priming in Broca's
      Aphasia.
AB  - This study tests the hypothesis that agrammatic comprehension is due to a
      computational rather than a structural language deficit. It is claimed that
      grammatic Broca's aphasics do not meet the temporal constraints in the activation
      of different types of linguistic information necessary for normal parsing. These
      temporal constraints are investigated in two experiments using a crossmodal
      syntactic priming paradigm. Each experiment tests the effect on recognition of
      grammatical versus ungrammatical links between an auditory sentence fragment (the
      prime) and a visually presented word (the target). The experiments differ in the
      interstimulus interval (ISI i.e., the amount of time provided between the offset
      of the auditory prime and the onset of the visuai target. Experiment 1, with an
      ISI of 0 msec, reveals that Broca patients - much like the control groups - show
      a grammaticality effect. In contrast to normal students and age matched controls,
      however, these patients are in general much slower in making lexical decisions
      when auditory context is present as compared to when visual targets are presented
      in isolation. Experiment 2 with an ISI of 200 msec demonstrates that when
      additional time is given to process the syntactic context, Broca's aphasics in
      contrast to age matched controls show faster decision times on the target than
      when the ISI is 0 msec. The results are in accord with the view that agrammatic
      Broca's aphasics have not lost their syntactic knowledge, but that their a
      grammatic comprehension behavior is due to the inability to process the
      linguistic information within a given time frame. More generally, the findings
      suggest that language processing can break down once activation of different
      types of linguistic information does not follow the normal time pattern. 

PMID- 23968510
TI  - Comparisons between Active Properties of Distal Dendritic Branches and Spines:
      Implications for Neuronal Computations.
AB  - The specific contributions of distal dendrites to the computational properties of
      cortical neurons are little understood and are completely ignored in most network
      simulations of higher brain functions. Compartmental models, based on realistic
      estimates of morphology and physiology, provide a means for exploring these
      contributions. We have pursued analysis of a model of synaptic integration in a
      distal dendrite bearing four spines, using a new general-purpose simulation
      program called SABER. We have analyzed this model under the assumption that the
      dendrite contains sites of impulse-generating membrane, and we have compared its
      responses to synaptic activation with the case of impulse-generating membrane
      located instead in the spine heads, as previously reported. Both types of models
      generate basic logic operations, such as AND, OR, and AND-NOT gates. Active spine
      heads require lower excitatory synaptic conductances, but active branch segments
      lead to larger responses in the soma. The transients recorded near the soma give
      no evidence of their origin in either active branch or active spines, indicating
      that the interpretation of experimental recordings with regard to sites of distal
      active responses must be viewed with caution. The results suggest the hypothesis
      that a hierarchy of logic operations is virtually inherent in the branching
      structure of dendritic trees of cortical pyramidal neurons. Inclusion of these
      properties in representations of cortical neurons would greatly enhance the
      computational power of neural networks aimed at simulating higher brain
      functions. 

PMID- 23968512
TI  - Automated spectrophotometric analyzer for rapid single-point titration of
      seawater total alkalinity.
AB  - An automated analyzer was developed to achieve fast, precise, and accurate
      measurements of seawater total alkalinity (AT) based on single-point titration
      and spectrophotometric pH detection. The single-point titration was carried out
      in a circulating loop, which allowed the titrant (hydrochloric acid and
      bromocresol green solution) and a seawater sample to mix at a constant volume
      ratio. The dissolved CO2 in the sample-titrant mixture was efficiently removed by
      an inline CO2 remover, which consists of a gas-permeable tubing (Teflon AF2400)
      submerged in a sodium hydroxide (NaOH) solution. The pH of the mixture was then
      measured with a custom-made spectrophotometric detection system. The analyzer was
      calibrated against multiple certified reference materials (CRMs) with different
      AT values. The analyzer features a sample throughput time of 6.5 min with high
      precision (+/-0.33-0.36 MUmol kg(-1); n = 48) and accuracy (-0.33 +/- 0.99 MUmol
      kg(-1); n = 10). Intercomparison to a traditional open-cell AT titrator showed
      overall good agreement of 0.88 +/- 2.03 MUmol kg(-1) (n = 22). The analyzer
      achieved excellent stability without recalibration over 11 days, during which
      time 320 measurements were made with a total running time of over 40 h. Because
      of its small size, low power consumption requirements, and its ability to be
      automated, the new analyzer can be adapted for underway and in situ measurements.

PMID- 23968513
TI  - Hysterosalpingocontrast sonography (HyCoSy): evaluation of the pain perception,
      side effects and complications.
AB  - BACKGROUND: Tubal and uterine cavity diseases commonly compromise female
      fertility. At the present time, hysteroscopy, laparoscopy with chromopertubation
      and RX-Hysterosalpingography (RX-HSG) are widely accepted screening procedures
      enabling the effective assessment of both tubal patency and uterine cavity.
      Nevertheless, consistent evidence supports the reliability of
      Hysterosalpingocontrast sonography (HyCoSy) in uterine cavity and tubal patency
      investigation, as a part of the standard infertility work-up. This prospective
      study was aimed at evaluating the tolerability of the technique as well as the
      incidence of related side effects and complications in a large series of
      infertile patients. METHODS: Pain perception of 632 infertile women was measured
      by means of an 11-point numeric rating scale. Side effects and late complications
      were also recorded. RESULTS: The mean numeric rating scale was 2.15 +/- 2.0 SD.
      Most of the patients (374/632, 59.17%) rated HyCoSy as a non-painful procedure,
      whereas 24.36% (154/632) women reported mild pelvic pain and 9.96% (63/632)
      classified the discomfort as "moderate". Only 6.48% (41/632) of the patient
      population experienced severe pelvic pain. Fifteen (2.37%) patients required drug
      administration for pain relief. Twenty-six patients (4.11%) showed mild vaso
      vagal reactions that resolved without atropine administration. No severe vaso
      vagal reactions or late complications were observed. CONCLUSIONS: HyCoSy is a
      well-tolerated examination and the associated vagal effects are unusual and
      generally mild. Consequently, we support its introduction as a first-line
      procedure for tubal patency and uterine cavity investigation in infertile women.

PMID- 23968533
TI  - Integrating child health services into malaria control services of village
      malaria workers in remote Cambodia: service utilization and knowledge of malaria
      management of caregivers.
AB  - BACKGROUND: Malaria and other communicable diseases remain major threats in
      developing countries. In Cambodia, village malaria workers (VMWs) have been
      providing malaria control services in remote villages to cope with the disease
      threats. In 2009, the VMW project integrated child health services into the
      original malaria control services. However, little has been studied about the
      utilization of VMWs' child health services. This study aimed to identify
      determinants of caregivers' VMW service utilization for childhood illness and
      caregivers' knowledge of malaria management. METHODS: A cross-sectional study was
      conducted in 36 VMW villages of Kampot and Kampong Thom provinces in July
      September 2012. An equal number of VMW villages with malaria control services
      only (M) and those with malaria control plus child health services (M+C) were
      selected from each province. Using structured questionnaires, 800 caregivers of
      children under five and 36 VMWs, one of the two VMWs who was providing VMW
      services in each study village were interviewed. RESULTS: Among the caregivers,
      23% in M villages and 52% in M+C villages utilized VMW services for childhood
      illnesses. Determinants of caregivers' utilization of VMWs in M villages included
      their VMWs' length of experience (AOR = 11.80, 95% confidence interval [CI] =
      4.46-31.19) and VMWs' service quality (AOR = 2.04, CI = 1.01-4.11). In M+C
      villages, VMWs' length of experience (AOR = 2.44, CI = 1.52-3.94) and caregivers'
      wealth index (AOR = 0.35, CI = 0.18-0.68) were associated with VMW service
      utilization. Meanwhile, better service quality of VMWs (AOR = 3.21, CI = 1.34
      7.66) and caregivers' literacy (AOR = 9.91, CI = 4.66-21.05) were positively
      associated with caregivers' knowledge of malaria management. CONCLUSIONS: VMWs'
      service quality and length of experience are important determinants of
      caregivers' utilization of VMWs' child health services and their knowledge of
      malaria management. Caregivers are seeking VMWs' support for childhood illnesses
      even if they are providing only malaria control services. This underlines the
      importance of scaling-up VMWs' capacity by adding child health services of good
      quality, which will result in improving child health status in remote Cambodia.

PMID- 23968534
TI  - Stereocontrolled synthesis of (E,Z)-dienals via tandem Rh(I)-catalyzed
      rearrangement of propargyl vinyl ethers.
AB  - A novel Rh(I)-catalyzed approach to functionalized (E,Z) dienals has been
      developed via tandem transformation where a stereoselective hydrogen transfer
      follows a propargyl Claisen rearrangement. Z-Stereochemistry of the first double
      bond suggests the involvement of a six-membered cyclic intermediate whereas the E
      stereochemistry of the second double bond stems from the subsequent
      protodemetalation step giving an (E,Z)-dienal. 

PMID- 23968535
TI  - Lyotropic liquid crystalline phases of a phytosterol ethoxylate in amide
      solvents.
AB  - Materials exhibiting unique aggregation behavior in nonaqueous solvents have
      attracted attention due to their wide applications. Motivated by this recent
      interest, the aggregation properties of a phytosterol ethoxylate surfactant, BPS
      10, in three organic amide compounds, formamide (FA), N-methylformamide (NMF),
      and N,N-dimethyl- formamide (DMF), have been studied. Polarized optical
      microscopy and small-angle X-ray scattering techniques were used to investigate
      the lyotropic liquid crystalline (LLC) phases formed in these binary systems.
      Herein, we discuss the relationship between subtle intermolecular interactions
      and the aggregation behavior of BPS-10. As good proton donors or acceptors to
      form hydrogen bonding, FA molecules allow BPS-10 to show a richer phase behavior.
      Compared with the systems formed in water and ionic liquids, the LLCs constructed
      in FA have higher thermal stability. In addition, two kinds of lamellar phases
      could coexist in a narrow region. With the methyl replacement in formamide,
      however, the ability to form hydrogen bonds is reduced and the solvent bulk phase
      structure becomes less ordered from FA to DMF. Consequently, the solvophobic
      interaction of BPS-10 becomes weaker, and the LLCs are more difficult to form. In
      addition, the extra strong interactions between the steroid rings of BPS-10 may
      provide enough driving force to produce the hexagonal phase (H1) directly in NMF
      and DMF without micelle formation, thereby creating a novel sequence (isotropic 
      > H1 -> Lalpha) of ordered phases with increasing surfactant concentration. The
      results discussed herein should prove to be a useful complement to the growing
      body of literature regarding steroid surfactant aggregation in polar organic
      solvents. 

PMID- 23968536
TI  - Skin tumors and skin infections in kidney transplant recipients vs. patients with
      pemphigus vulgaris.
AB  - BACKGROUND: Pemphigus vulgaris is an autoimmune disease of the skin and mucous
      membrane. Renal transplantation is a common procedure in Iraq, and these patients
      required prolonged use of immunosuppressive drugs. OBJECTIVE: To study the
      frequency of skin tumors and infections in patients with pemphigus vulgaris
      compared with renal transplant recipients and normal controls. PATIENTS AND
      METHODS: One hundred kidney transplant recipients, their ages ranged from 14 to
      70 (46.65 +/- 4.74) years, and 50 patients with pemphigus vulgaris, their ages
      ranged from 22 to 70 (43.32 +/- 3.46) years, were studied in Baghdad Hospital
      from June 2009 to August 2010. Patients were treated with immunosuppressive drugs
      for 0.5-25 years. Patients were examined for tumors and infections and compared
      with the general population as controls (100 individuals). RESULTS: In renal
      transplant recipients, the following infections were observed: herpetic, 25
      patients (25%); bacterial, 11 (11%); and fungal, 22 (22%). These infections
      appeared early in the course of immunosuppression. Benign tumors increased, most
      importantly viral warts in 40 (40%) and actinic keratosis, 14 (14%). The
      malignant tumors were basal cell carcinomas in 4 (4%), squamous cell carcinomas 2
      (2%), and Kaposi's sarcoma 3 (3%). These malignancies usually appeared late in
      the course of immunosuppression. Patients with pemphigus vulgaris showed no
      important skin infections or tumors. Healthy controls showed no infections apart
      from herpetic infections in 7 (7%) and viral warts in 9 (9%). No tumors were
      seen. CONCLUSIONS: Pemphigus vulgaris in prolonged immunosuppression is
      immunoprotective against skin infections and skin tumors while kidney transplant
      recipients are not protective.

PMID- 23968537
TI  - Benzothiazole aniline tetra(ethylene glycol) and 3-amino-1,2,4-triazole inhibit
      neuroprotection against amyloid peptides by catalase overexpression in vitro.
AB  - Alzheimer's disease, Familial British dementia, Familial Danish dementia, Type 2
      diabetes mellitus, plus Creutzfeldt-Jakob disease are associated with amyloid
      fibril deposition and oxidative stress. The antioxidant enzyme catalase is a
      neuroprotective amyloid binding protein. Herein the effects of catalase
      overexpression in SH-SY5Y neuronal cells on the toxicity of amyloid-beta (Abeta),
      amyloid-Bri (ABri), amyloid-Dan (ADan), amylin (IAPP), and prion protein (PrP)
      peptides were determined. Results showed catalase overexpression was
      neuroprotective against Abeta, ABri, ADan, IAPP, and PrP peptides. The catalase
      inhibitor 3-amino-1,2,4-triazole (3-AT) and catalase-amyloid interaction
      inhibitor benzothiazole aniline tetra(ethylene glycol) (BTA-EG4) significantly
      enhanced neurotoxicity of amyloid peptides in catalase overexpressing neuronal
      cells. This suggests catalase neuroprotection involves breakdown of hydrogen
      peroxide (H2O2) plus a direct binding interaction between catalase and the Abeta,
      ABri, ADan, IAPP, and PrP peptides. Kisspeptin 45-50 had additive neuroprotective
      actions against the Abeta peptide in catalase overexpressing cells. The effects
      of 3-AT had an intracellular site of action, while catalase-amyloid interactions
      had an extracellular component. These results suggest that the 3-AT and BTA-EG4
      compounds may be able to inhibit endogenous catalase mediated neuroprotection.
      Use of BTA-EG4, or compounds that inhibit catalase binding to amyloid peptides,
      as potential therapeutics for Neurodegenerative diseases may therefore result in
      unwanted effects. 

PMID- 23968538
TI  - Biodiversity ensures plant-pollinator phenological synchrony against climate
      change.
AB  - Climate change has the potential to alter the phenological synchrony between
      interacting mutualists, such as plants and their pollinators. However, high
      levels of biodiversity might buffer the negative effects of species-specific
      phenological shifts and maintain synchrony at the community level, as predicted
      by the biodiversity insurance hypothesis. Here, we explore how biodiversity might
      enhance and stabilise phenological synchrony between a valuable crop, apple and
      its native pollinators. We combine 46 years of data on apple flowering phenology
      with historical records of bee pollinators over the same period. When the key
      apple pollinators are considered altogether, we found extensive synchrony between
      bee activity and apple peak bloom due to complementarity among bee species'
      activity periods, and also a stable trend over time due to differential responses
      to warming climate among bee species. A simulation model confirms that high
      biodiversity levels can ensure plant-pollinator phenological synchrony and thus
      pollination function.

PMID- 23968539
TI  - The angiogenic factors and their soluble receptors in sepsis: friend, foe, or
      both?

PMID- 23968541
TI  - Resuscitation and auto resuscitation by airway reflexes in animals.
AB  - Various diseases often result in decompensation requiring resuscitation. In
      infants moderate hypoxia evokes a compensatory augmented breath - sigh and more
      severe hypoxia results in a solitary gasp. Progressive asphyxia provokes gasping
      respiration saving the healthy infant - autoresuscitation by gasping. A neonate
      with sudden infant death syndrome, however, usually will not survive. Our
      systematic research in animals indicated that airway reflexes have similar
      resuscitation potential as gasping respiration. Nasopharyngeal stimulation in
      cats and most mammals evokes the aspiration reflex, characterized by spasmodic
      inspiration followed by passive expiration. On the contrary, expiration reflex
      from the larynx, or cough reflex from the pharynx and lower airways manifest by a
      forced expiration, which in cough is preceded by deep inspiration. These reflexes
      of distinct character activate the brainstem rhythm generators for inspiration
      and expiration strongly, but differently. They secondarily modulate the control
      mechanisms of various vital functions of the organism. During severe asphyxia the
      progressive respiratory insufficiency may induce a life-threatening cardio
      respiratory failure. The sniff- and gasp-like aspiration reflex and similar
      spasmodic inspirations, accompanied by strong sympatho-adrenergic activation, can
      interrupt a severe asphyxia and reverse the developing dangerous cardiovascular
      and vasomotor dysfunctions, threatening with imminent loss of consciousness and
      death. During progressive asphyxia the reversal of gradually developing
      bradycardia and excessive hypotension by airway reflexes starts with reflex
      tachycardia and vasoconstriction, resulting in prompt hypertensive reaction,
      followed by renewal of cortical activity and gradual normalization of breathing.
      A combination of the aspiration reflex supporting venous return and the
      expiration or cough reflex increasing the cerebral perfusion by strong
      expirations, provides a powerful resuscitation and autoresuscitation potential,
      proved in animal experiments. They represent a simple but unique model tested in
      animal experiments. 

PMID- 23968542
TI  - ITIM-dependent negative signaling pathways for the control of cell-mediated
      xenogeneic immune responses.
AB  - Xenotransplantation is an innovative field of research with the potential to
      provide us with an alternative source of organs to face the severe shortage of
      human organ donors. For several reasons, pigs have been chosen as the most
      suitable source of organs and tissues for transplantation in humans. However,
      porcine xenografts undergo cellular immune responses representing a major barrier
      to their acceptance and normal functioning. Innate and adaptive xenogeneic
      immunity is mediated by both the recognition of xenogeneic tissue antigens and
      the lack of inhibition due to molecular cross-species incompatibilities of
      regulatory pathways. Therefore, the delivery of immunoreceptor tyrosine-based
      inhibitory motif (ITIM)-dependent and related negative signals to control innate
      (NK cells, macrophages) and adaptive T and B cells might overcome cell-mediated
      xenogeneic immunity. The proof of this concept has already been achieved in vitro
      by the transgenic overexpression of human ligands of several inhibitory receptors
      in porcine cells resulting in their resistance against xenoreactivity.
      Consequently, several transgenic pigs expressing tissue-specific human ligands of
      inhibitory coreceptors (HLA-E, CD47) or soluble competitors of costimulation
      (belatacept) have already been generated. The development of these robust and
      innovative approaches to modulate human anti-pig cellular immune responses,
      complementary to conventional immunosuppression, will help to achieve long-term
      xenograft survival. In this review, we will focus on the current strategies to
      enhance negative signaling pathways for the regulation of undesirable cell
      mediated xenoreactive immune responses. 

PMID- 23968540
TI  - Antigenic and molecular characterization of avian influenza A(H9N2) viruses,
      Bangladesh.
AB  - Human infection with avian influenza A(H9N2) virus was identified in Bangladesh
      in 2011. Surveillance for influenza viruses in apparently healthy poultry in live
      bird markets in Bangladesh during 2008-2011 showed that subtype H9N2 viruses are
      isolated year-round, whereas highly pathogenic subtype H5N1 viruses are co
      isolated with subtype H9N2 primarily during the winter months. Phylogenetic
      analysis of the subtype H9N2 viruses showed that they are reassortants possessing
      3 gene segments related to subtype H7N3; the remaining gene segments were from
      the subtype H9N2 G1 clade. We detected no reassortment with subtype H5N1 viruses.
      Serologic analyses of subtype H9N2 viruses from chickens revealed antigenic
      conservation, whereas analyses of viruses from quail showed antigenic drift.
      Molecular analysis showed that multiple mammalian-specific mutations have become
      fixed in the subtype H9N2 viruses, including changes in the hemagglutinin,
      matrix, and polymerase proteins. Our results indicate that these viruses could
      mutate to be transmissible from birds to mammals, including humans.

PMID- 23968543
TI  - Inhibition of Janus kinase/signal transducer and activator of transcription
      (JAK/STAT) signalling pathway in rheumatoid synovial fibroblasts using small
      molecule compounds.
AB  - Janus kinase (JAK) inhibitors have been developed as anti-inflammatory agents and
      have demonstrated clinical efficacy in rheumatoid arthritis (RA). We investigated
      if JAK-3-selective inhibition alone could disrupt cytokine signalling in
      rheumatoid synovial fibroblasts. In-vitro studies were performed using synovial
      fibroblasts isolated from patients with RA. Levels of activated JAK and signal
      transducer and activator of transcription (STAT) proteins were detected by
      immunoblot analysis. Target-gene expression levels were measured by reverse
      transcription-polymerase chain reaction (RT-PCR) or real-time PCR. The JAK
      inhibitors CP-690,550 and INCB028050 both suppressed activation of JAK-1/-2/-3
      and downstream STAT-1/-3/-5, as well as the expression levels of target
      proinflammatory genes (MCP-I, SAA1/2) in oncostatin-M (OSM)-stimulated rheumatoid
      synovial fibroblasts. In contrast, the JAK-3-selective inhibitor, PF-956980,
      suppressed STAT-1/-5 activation but did not affect STAT-3 activation in OSM
      stimulated rheumatoid synovial fibroblasts. In addition, PF-956980 significantly
      suppressed MCP-1 gene expression, but did not block SAA1/2 gene expression in OSM
      stimulated rheumatoid synovial fibroblasts. These data suggest that JAK-3
      selective inhibition alone is insufficient to control STAT-3-dependent signalling
      in rheumatoid synovial fibroblasts, and inhibition of JAKs, including JAK-1/-2,
      is needed to control the proinflammatory cascade in RA. 

PMID- 23968544
TI  - Stationary phase and mature infectious forms of Legionella pneumophila produce
      distinct viable but non-culturable cells.
AB  - Legionella pneumophila is an intracellular bacterial parasite of freshwater
      protozoa and an accidental waterborne human pathogen. L. pneumophila is highly
      pleomorphic showing several forms that differentiate within its developmental
      cycle. In water, L. pneumophila produces viable but non-culturable cells
      (VBNCCs), which remain largely uncharacterized. We produced VBNCCs from two
      developmental forms of L. pneumophila [stationary phase forms (SPFs) and mature
      infectious forms (MIFs)] in two water microcosms [double-deionized (dd) and tap
      water] at 45 degrees C. In contrast with SPFs, MIFs upheld a robust
      ultrastructure and high viability in the two water microcosms. In dd-water, MIFs
      and SPFs lost their culturability faster than in tap water and did not consume
      their poly-beta-hydroxybutyrate inclusions. Resuscitation in Acanthamoeba
      castellani was only possible for VBNCCs produced from SPFs in tap water. Addition
      of salts to dd-water prolonged L. pneumophila culturability to tap water levels,
      suggesting that L. pneumophila requires ions to maintain its readiness to resume
      growth. VBNCCs resisted detergent lysis and digestion in the ciliate Tetrahymena,
      except for VBNCCs produced from SPFs in dd-water. L. pneumophila VBNCCs thus show
      distinct traits according to its originating developmental form and the
      surrounding water microcosm. 

PMID- 23968545
TI  - Melanoma in skin of color in Connecticut: an analysis of melanoma incidence and
      stage at diagnosis in non-Hispanic blacks, non-Hispanic whites, and Hispanics.
AB  - BACKGROUND: The incidence of melanoma is increasing in Caucasians and in Hispanic
      subgroups in California and Florida. There is a paucity of information regarding
      melanoma incidence, stage at diagnosis, and other patient and tumor factors among
      minority subgroups in the northeast USA. This report examines melanoma in non
      Hispanic white, non-Hispanic black, and Hispanic residents of Connecticut.
      METHODS: Trends in age-adjusted melanoma incidence rates (1992-2007) and the
      corresponding annual percentage changes in rates were calculated for Connecticut
      residents by race and Hispanic ethnicity. The racial/ethnic variation was
      evaluated for a number of patient and tumor characteristics: gender, age at
      diagnosis, marital status, anatomic site, histology, ulceration, Breslow
      thickness, and stage at diagnosis. Statistical significance at the 95% level was
      assessed using confidence intervals (95% CIs) and Pearson's chi-squared tests.
      RESULTS: Between 1992 and 2007, melanoma incidence increased by 4.1% per year in
      non-Hispanic whites in Connecticut (95% CI 3.1-5.1%; P<0.05). Melanoma incidence
      remained relatively stable for Hispanics and non-Hispanic blacks over the same
      period. A significantly higher proportion of advanced (regional and distant)
      melanomas were diagnosed in non-Hispanic blacks (19.1%) and Hispanics (17.1%)
      than in non-Hispanic whites (8.7%) (P<0.001). CONCLUSIONS: A significantly higher
      proportion of advanced melanomas were diagnosed in non-Hispanic blacks and
      Hispanics than in non-Hispanic whites. There is a growing need to educate
      patients and healthcare providers of the necessity for skin cancer surveillance
      regardless of the race of the patient.

PMID- 23968546
TI  - Percutaneous endoscopic discectomy and thermal annuloplasty for professional
      athletes.
AB  - INTRODUCTION: Percutaneous endoscopic discectomy (PED) for herniated nucleus
      pulposus has become increasingly popular since first reported by Yeung and Tsou.
      Additionally, radiofrequency thermal annuloplasty (TA) with PED (PED/TA) has been
      reported to be effective for discogenic low back pain. We used the PED/TA
      procedure to successfully treat four professional athletes with discogenic low
      back pain. METHODS: All patients were men; their age at operation was 35, 35, 34,
      and 28 years. Daily low back pain was provoked by discography in all four
      patients, who had been receiving conservative but ineffective treatment for over
      1 year. Surgery was conducted with the patients under local anesthesia. A cannula
      was placed posterior to the disc and ventral to the posterior annulus fibrosus
      through a 7-mm skin incision. Degenerated nucleus pulposus at the site was
      removed percutaneously and the posterior annulus was modulated by bipolar
      radiofrequency TA. RESULTS: After surgery, low back pain was resolved in all
      cases. After effective post-surgical rehabilitation with a physical trainer or
      physical therapist, all patients returned to their original competitive level.
      CONCLUSION: PED/TA is a minimally invasive and effective procedure for discogenic
      low back pain, especially in athletes.

PMID- 23968547
TI  - Comparison of weight- vs body surface area-based growth hormone dosing for
      children: implications for response.
AB  - OBJECTIVE: To compare weight (per kg)- vs body surface area (BSA, per m(2) )
      based growth hormone (GH) dosing formats in children and to derive a useful
      conversion formula between the two formats. PATIENTS AND DESIGN: Growth hormone
      doses (>33,000) from 1874 children were obtained from the national Australian
      database (OZGROW) and used to derive conversion formulae and to confirm the
      accuracy of a conversion formula based on a weight-only BSA estimate. A further
      27,000 doses were used to test the accuracy of all formulae. The best conversion
      formula was used to compare weight- and surface area-based GH dosing, which
      included an analysis of first year response (?SDS height or growth velocity, GV).
      MEASUREMENTS: Growth hormone doses in mg/m(2) /wk and mg/kg/wk, dose estimates,
      residuals, first year ?SDS, first year GV. RESULTS: The formula, [Formula: see
      text] based on a weight-only BSA estimate, provides accurate dose conversion
      (mean residual, 0.005 mg/kg/week). A constant mg/m(2) /week dose expressed in
      terms of mg/kg/week declines quickly with increasing body weight to approximately
      15 kg after which the decline continues although less dramatically. For
      Australian patients, despite an increase in mean per m(2) dose with increased
      starting weight/age, the per kg dose decreased. This was associated with a
      greater decline in first year GV than estimated if a per kg dose had been
      maintained. CONCLUSIONS: Growth hormone doses can be accurately converted between
      formats. Surface area-based GH dosing is likely to result in a reduced height
      response as children become heavier when compared with weight-based GH dosing.

PMID- 23968548
TI  - AT1 antagonists: a patent review (2008 - 2012).
AB  - INTRODUCTION: For two decades a class of pharmaceutical molecules with proved
      beneficial therapeutic properties, especially in hypertension, has been
      introduced in the market aiming to specifically prevent the detrimental effects
      of the peptide hormone Angiotensin II at the AT1 receptor. The prototype of this
      class was losartan and based on its structure, several drugs were launched and
      also called 'Sartans'. New structural features on these molecules can provide
      multi-target properties in the RAS or other systems. New methodologies were
      developed for the treatment of hypertension utilizing either AT1 antagonists
      alone or as cocktails. AREAS COVERED: In this review article, authors aim to
      cover information provided by patents of the years 2008 - 2012. The rationale of
      writing this review article is to cover the most important patents which can
      forward the field with new important discoveries. EXPERT OPINION: From the patent
      investigation it is clear that new areas on the subject are still offered for new
      discoveries. New structural features can be still considered in the synthetic
      compounds that can advance the knowledge and beneficial effects on diseases
      related to Angiotensin II and AT1 receptor. There is era also for new
      formulations (i.e., cyclodextrins, polymers and liposomes). The multitarget
      approach can be further strengthened and more combinations can be sought in the
      rational drug design for seeking cocktails. Furthermore, the revealing of the
      complexity of the RAS offers new avenues for novel targets and this must not be
      overlooked.

PMID- 23968549
TI  - Trimetallic borohydride Li3MZn5(BH4)15 (M = Mg, Mn) containing two weakly
      interconnected frameworks.
AB  - The compounds, Li3MZn5(BH4)15, M = Mg and Mn, represent the first trimetallic
      borohydrides and are also new cationic solid solutions. These materials were
      prepared by mechanochemical synthesis from LiBH4, MCl2 or M(BH4)2, and ZnCl2. The
      compounds are isostructural, and their crystal structure was characterized by in
      situ synchrotron radiation powder X-ray and neutron diffraction and DFT
      calculations. While diffraction provides an average view of the structure as
      hexagonal (a = 15.371(3), c = 8.586(2) A, space group P63/mcm for Mg-compound at
      room temperature), the DFT optimization of locally ordered models suggests a
      related ortho-hexagonal cell. Ordered models that maximize Mg-Mg separation have
      the lowest DFT energy, suggesting that the hexagonal structure seen by
      diffraction is a superposition of three such orthorhombic structures in three
      orientations along the hexagonal c-axis. No conclusion about the coherent length
      of the orthorhombic structure can be however done. The framework in
      Li3MZn5(BH4)15 is of a new type. It contains channels built from face-sharing
      (BH4)6 octahedra. While X-ray and neutron powder diffraction preferentially
      localize lithium in the center of the octahedra, thus resulting in two weakly
      interconnected frameworks of a new type, the DFT calculations clearly favor
      lithium inside the shared triangular faces, leading to two interpenetrated mco
      nets (mco-c type) with the basic tile being built from three tfa tiles, which is
      the framework type of the related bimetallic LiZn2(BH4)5. The new borohydrides
      Li3MZn5(BH4)15 are potentially interesting as solid-state electrolytes, if the
      lithium mobility within the octahedral channels is improved by disordering the
      site via heterovalent substitution. From a hydrogen storage point of view, their
      application seems to be limited as the compounds decompose to three known metal
      borohydrides. 

PMID- 23968550
TI  - High-temperature shock tube and modeling studies on the reactions of methanol
      with D-atoms and CH3-radicals.
AB  - The shock tube technique has been used to study the hydrogen abstraction
      reactions D + CH3OH -> CH2O + H + HD (A) and CH3 + CH3OH -> CH2O + H + CH4 (B).
      For reaction A, the experiments span a T-range of 1016 K <= T <= 1325 K, at
      pressures 0.25 bar <= P <= 0.46 bar. The experiments on reaction B, CH3 + CH3OH,
      cover a T-range of 1138 K <= T <= 1270 K, at pressures around 0.40 bar. Reflected
      shock tube experiments, monitoring the depletion of D-atoms by applying D-atom
      atomic resonance absorption spectrometry (ARAS), were performed on reaction A
      using gas mixtures of C2D5I and CH3OH in Kr bath gas. C2D5I was used as precursor
      for D-atoms. For reaction B, reflected shock tube experiments monitoring H-atom
      formation with H-ARAS, were carried out using gas mixtures of diacetyl ((CH3CO)2)
      and CH3OH in Kr bath gas. (CH3CO)2 was used as the source of CH3-radicals.
      Detailed reaction models were assembled to fit the D-atom and H-atom time
      profiles in order to obtain experimental rate constants for reactions A and B.
      Total rate constants from the present experiments on D + CH3OH and CH3 + CH3OH
      can be represented by the Arrhenius equations kA(T) = 1.51 * 10(-10) exp(-3843
      K/T) cm(3) molecules(-1) s(-1) (1016 K <= T <= 1325 K) and kB(T) = 9.62 * 10(-12)
      exp(-7477 K/T) cm(3) molecules(-1) s(-1) (1138 K <= T <= 1270 K). The
      experimentally obtained rate constants were compared with available rate data
      from the literature. The results from quantum chemical studies on reaction A were
      found to be in good agreement with the present results. The present work
      represents the first direct experimental study on these bimolecular reactions at
      combustion temperatures and is important to the high-temperature oxidation of
      CH3OH. 

PMID- 23968551
TI  - New nucleotide-competitive non-nucleoside inhibitors of terminal deoxynucleotidyl
      transferase: discovery, characterization, and crystal structure in complex with
      the target.
AB  - Terminal deoxynucletidyl transferase (TdT) is overexpressed in some cancer types,
      where it might compete with pol MU during the mutagenic repair of double strand
      breaks (DSBs) through the nonhomologous end joining (NHEJ) pathway. Here we
      report the discovery and characterization of pyrrolyl and indolyl diketo acids
      that specifically target TdT and behave as nucleotide-competitive inhibitors.
      These compounds show a selective toxicity toward MOLT-4 compared to HeLa cells
      that correlate well with in vitro selectivity for TdT. The binding site of two of
      these inhibitors was determined by cocrystallization with TdT, explaining why
      these compounds are competitive inhibitors of the deoxynucleotide triphosphate
      (dNTP). In addition, because of the observed dual localization of the phenyl
      substituent, these studies open the possibility of rationally designing more
      potent compounds. 

PMID- 23968552
TI  - Rh(III)-catalyzed tandem C-H allylation and oxidative cyclization of anilides: a
      new entry to indoles.
AB  - Rh(III)-catalyzed tandem C-H allylation and oxidative cyclization of anilides
      with allyl carbonates in the presence of a slight excess of AgSbF6 salt and
      Cu(OAc)2 as oxidant affords easy, economical access to important bioactive 2
      methylindoles. The new reaction supports a wide range of functional groups on the
      anilide substrate. A possible mechanism is proposed as a basis for its rational
      further development. 

PMID- 23968553
TI  - Green manure plants for remediation of soils polluted by metals and metalloids:
      ecotoxicity and human bioavailability assessment.
AB  - Borage, white mustard and phacelia, green manure plants currently used in
      agriculture to improve soil properties were cultivated for 10 wk on various
      polluted soils with metal(loid) concentrations representative of urban
      brownfields or polluted kitchen gardens. Metal(loid) bioavailability and
      ecotoxicity were measured in relation to soil characteristics before and after
      treatment. All the plants efficiently grow on the various polluted soils. But
      borage and mustard only are able to modify the soil characteristics and
      metal(loid) impact: soil respiration increased while ecotoxicity, bioaccessible
      lead and total metal(loid) quantities in soils can be decreased respectively by
      phytostabilization and phytoextraction mechanisms. These two plants could
      therefore be used for urban polluted soil refunctionalization. However, plant
      efficiency to improve soil quality strongly depends on soil characteristics.

PMID- 23968554
TI  - Factors affecting temporal H2S emission at construction and demolition (C&D)
      debris landfills.
AB  - Odor problems associated with H2S emissions often result in odor complaints from
      nearby residents of C&D debris landfills, especially in the early morning. As
      part of a field study conducted on H2S removal ability using different cover
      materials, daily and seasonal H2S emissions through a soil cover layer were
      monitored at a C&D debris landfill to investigate factors affecting H2S
      emissions. H2S emission rates were not a constant, but varied seasonally, with an
      average emission rate of 4.67*10(-6)mgm(-2)s(-1). During a the 10-month field
      study, as the H2S concentration increased from 140ppm to about 3500ppm underneath
      the cover soil in the testing cell, H2S emissions ranged from zero to a maximum
      emission rate of 1.24*10(-5)mgm(-2)s(-1). Continuous emission monitoring
      indicated that H2S emissions even changed over time throughout the day, generally
      increasing from morning to afternoon, and were affected by soil moisture and
      temperature. Laboratory experiments were also conducted to investigate the
      effects of H2S concentration and cover soil moisture content on H2S emissions.
      The results showed that increased soil moisture reduced H2S emissions by
      retarding H2S migration through cover soil and dissolving H2S into soil water.
      The field study also indicated that due to atmospheric dispersion, high H2S
      emissions may not cause odor problems. 

PMID- 23968555
TI  - Men and women adopt similar walking mechanics and muscle activation patterns
      during load carriage.
AB  - Although numerous studies have investigated the effects of load carriage on gait
      mechanics, most have been conducted on active military men. It remains unknown
      whether men and women adapt differently to carrying load. The purpose of this
      study was to compare the effects of load carriage on gait mechanics, muscle
      activation patterns, and metabolic cost between men and women walking at their
      preferred, unloaded walking speed. We measured whole body motion, ground reaction
      forces, muscle activity, and metabolic cost from 17 men and 12 women. Subjects
      completed four walking trials on an instrumented treadmill, each five minutes in
      duration, while carrying no load or an additional 10%, 20%, or 30% of body
      weight. Women were shorter (p<0.01), had lower body mass (p=0.01), and had lower
      fat-free mass (p=0.02) compared to men. No significant differences between men
      and women were observed for any measured gait parameter or muscle activation
      pattern. As load increased, so did net metabolic cost, the duration of stance
      phase, peak stance phase hip, knee, and ankle flexion angles, and all peak joint
      extension moments. The increase in the peak vertical ground reaction force was
      less than the carried load (e.g. ground force increased approximately 6% with
      each 10% increase in load). Integrated muscle activity of the soleus, medial
      gastrocnemius, lateral hamstrings, vastus medialis, vastus lateralis, and rectus
      femoris increased with load. We conclude that, despite differences in
      anthropometry, men and women adopt similar gait adaptations when carrying load,
      adjusted as a percentage of body weight. 

PMID- 23968556
TI  - alpha1,3Galactosyltransferase knockout pigs produce the natural anti-Gal antibody
      and simulate the evolutionary appearance of this antibody in primates.
AB  - BACKGROUND: Anti-Gal is the most abundant natural antibody in humans and Old
      World primates (apes and Old World monkeys). Its ligand, the alpha-gal epitope
      (Galalpha1-3Galbeta1-4GlcNAc-R), is abundant in nonprimate mammals, prosimians
      and New World monkeys whereas it is absent in humans and Old World primates as a
      result of inactivation of the alpha1,3galactosyltransferase (alpha1,3GT) gene in
      ancestral Old World primates, as recent as 20-28 million years ago. Since anti
      Gal has been a "forbidden" autoantibody for >140 million years of evolution in
      mammals producing alpha-gal epitopes it was of interest to determine whether
      ancestral Old World primates could produce anti-Gal once alpha-gal epitopes were
      eliminated, i.e. did they carry anti-Gal encoding immunoglobulin genes, or did
      evolutionary selection eliminate these genes that may be detrimental in mammals
      synthesizing alpha-gal epitopes. This question was studied by evaluating anti-Gal
      prodution in alpha1,3GT knockout (GT-KO) pigs recently generated from wild-type
      pigs in which the alpha-gal epitope is a major self-antigen. METHODS: Anti-Gal
      antibody activity in pig sera was assessed by ELISA, flow cytometry and
      complement mediated cytolysis and compared to that in human sera. RESULTS: The
      study demonstrates abundant production of the natural anti-Gal antibody in GT-KO
      pigs at titers even higher than in humans. The fine specificity of GT-KO pig anti
      Gal is identical to that of human anti-Gal. CONCLUSIONS: Pigs and probably other
      mammals producing alpha-gal epitopes carry immunoglobulin genes encoding anti-Gal
      as an autoantibody. Once the alpha-gal epitope is eliminated in GT-KO pigs, they
      produce anti-Gal. These findings strongly suggest that similar to GT-KO pigs,
      inactivation of the alpha1,3GT gene in ancestral Old World primates enabled the
      immediate production of anti-Gal, possibly as a protective antibody against
      detrimental microbial agents carrying alpha-gal epitopes.

PMID- 23968557
TI  - Novel cyclovirus in human cerebrospinal fluid, Malawi, 2010-2011.
AB  - To identify unknown human viruses, we analyzed serum and cerebrospinal fluid
      samples from patients with unexplained paraplegia from Malawi by using viral
      metagenomics. A novel cyclovirus species was identified and subsequently found in
      15% and 10% of serum and cerebrospinal fluid samples, respectively. These data
      expand our knowledge of cyclovirus diversity and tropism.

PMID- 23968558
TI  - Multicentric paraspinal neuroglial heterotopia with Mullerian and renal agenesis:
      a variant of Mayer-Rokitansky-Kuster-Hauser syndrome?
AB  - Neuroglial heterotopia is a rare congenital anomaly that mostly involves the head
      and neck region. We report a female fetus with multicentric paraspinal neuroglial
      heterotopia in the retropharyngeal and retroperitoneal spaces, right renal
      agenesis, left renal hypoplasia, and Mullerian agenesis. Additional findings
      included bilateral preaxial polydactyly of the hands, megacystis, rectovesical
      fistula, and imperforate anus. The karyotype was 46, XX. This fetus had the
      features of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome with paraspinal
      neuroglial heterotopia. This is the first report of the co-occurrence of these
      two malformations which could share a common pathogenetic mechanism. We suggest
      this to be a variant MRKH syndrome. VIRTUAL SLIDES: The virtual slide(s) for this
      article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/3246922721015286.

PMID- 23968559
TI  - Scanty microbes, the 'symbionelle' concept.

PMID- 23968560
TI  - One calcitriol dose transiently increases Helios+ FoxP3+ T cells and ameliorates
      autoimmune demyelinating disease.
AB  - Multiple sclerosis (MS) is an incurable inflammatory demyelinating disease. We
      investigated one calcitriol dose plus vitamin D3 (calcitriol/+D) as a
      demyelinating disease treatment in experimental autoimmune encephalomyelitis
      (EAE). Evidence that calcitriol-vitamin D receptor pathway deficits may promote
      MS, and data showing calcitriol enhancement of autoimmune T cell apoptosis
      provided the rationale. Whereas vitamin D3 alone was ineffective, calcitriol/+D
      transiently increased central nervous system (CNS) Helios(+)FoxP3(+) T cells and
      sustainably decreased CNS T cells, pathology, and neurological deficits in mice
      with EAE. Calcitriol/+D, which was more effective than methylprednisolone, has
      potential for reversing inflammatory demyelinating disease safely and cost
      effectively. 

PMID- 23968561
TI  - CX3CL1 protects neurons against excitotoxicity enhancing GLT-1 activity on
      astrocytes.
AB  - In this paper we show for the first time that: i) astrocytes are required for the
      neuroprotective activity of CX3CL1 against excitotoxicity; ii) inhibition of the
      glutamate transporter 1 (GLT-1) prejudices CX3CL1-mediated neuroprotection; iii)
      CX3CL1 increases GLT-1 activity on astrocytes. The modulation of GLT-1 activity
      induced by CX3CL1 on astrocytes requires the presence and the activity of A1
      adenosine receptor (A1R), being blocked by the specific antagonist DPCPX and
      absent in A1R(-/-) astrocytes. These data introduce the astrocytes as active
      players in CX3CL1-mediated signaling between microglia and neurons, identifying
      GLT-1 as a key mediator of the neuroprotective activity of CX3CL1. 

PMID- 23968562
TI  - Rapamycin has suppressive and stimulatory effects on human plasmacytoid dendritic
      cell functions.
AB  - Plasmacytoid dendritic cells (PDC) are involved in innate immunity by interferon
      (IFN)-alpha production, and in adaptive immunity by stimulating T cells and
      inducing generation of regulatory T cells (Treg ). In this study we studied the
      effects of mammalian target of rapamycin (mTOR) inhibition by rapamycin, a
      commonly used immunosuppressive and anti-cancer drug, on innate and adaptive
      immune functions of human PDC. A clinically relevant concentration of rapamycin
      inhibited Toll-like receptor (TLR)-7-induced IFN-alpha secretion potently (-64%)
      but TLR-9-induced IFN-alpha secretion only slightly (-20%), while the same
      concentration suppressed proinflammatory cytokine production by TLR-7-activated
      and TLR-9-activated PDC with similar efficacy. Rapamycin inhibited the ability of
      both TLR-7-activated and TLR-9-activated PDC to stimulate production of IFN-gamma
      and interleukin (IL)-10 by allogeneic T cells. Surprisingly, mTOR-inhibition
      enhanced the capacity of TLR-7-activated PDC to stimulate naive and memory T
      helper cell proliferation, which was caused by rapamycin-induced up-regulation of
      CD80 expression on PDC. Finally, rapamycin treatment of TLR-7-activated PDC
      enhanced their capacity to induce CD4(+) forkhead box protein 3 (FoxP3)(+)
      regulatory T cells, but did not affect the generation of suppressive CD8(+)
      CD38(+) lymphocyte activation gene (LAG)-3(+)  Treg . In general, rapamycin
      inhibits innate and adaptive immune functions of TLR-stimulated human PDC, but
      enhances the ability of TLR-7-stimulated PDC to stimulate CD4(+) T cell
      proliferation and induce CD4(+) FoxP3(+) regulatory T cell generation. 

PMID- 23968563
TI  - [Clinical features of pulmonary embolism in elderly: a comparative study of 64
      patients].
AB  - PURPOSE: To date only a few studies regarding pulmonary embolism (PE) in elderly
      have been published. The aim of this study was to determine the clinical features
      of PE in elderly patients (>= 75 years). METHODS: All patients hospitalized for
      PE in our internal medicine department from January 2005 to December 2010 were
      included in the study. The aim was to compare the features of PE in elderly
      patients (>= 75 years) to those of patients younger than 75 years. The following
      data were recorded: past medical history, risk factors for venous thrombo
      embolism (VTE), clinical features, and PE etiologies. RESULTS: The population was
      composed of 64 patients (women 56%) with a median age of 82 years (IQR: 13.5).
      There was no statistical difference for risk factors of VTE. Syncope was more
      frequent in elderly patients (33% versus 7%, P=0.04) whereas thoracic pain
      predominated in younger patients (36,5% versus 7%, P=0.005). Chronic obstructive
      pulmonary disease was more frequent in the past medical history of elderly
      patients. The diagnostic of PE was less suspected in elderly patients (47% versus
      72%, P=0.035). The etiologies were similar between the two groups. CONCLUSION:
      Our study highlights the frequency of syncope as the presenting feature of PE in
      elderly, whereas thoracic pain is uncommon. We confirmed the difficulty to
      diagnose PE in elderly population.

PMID- 23968565
TI  - A versatile approach to Ullmann C-N couplings at room temperature: new families
      of nucleophiles and electrophiles for photoinduced, copper-catalyzed processes.
AB  - The use of light to facilitate copper-catalyzed cross-couplings of nitrogen
      nucleophiles can enable C-N bond formation to occur under unusually mild
      conditions. In this study, we substantially expand the scope of such processes,
      establishing that this approach is not limited to reactions of carbazoles with
      iodobenzene and alkyl halides. Specifically, we demonstrate for the first time
      that other nitrogen nucleophiles (e.g., common pharmacophores such as indoles,
      benzimidazoles, and imidazoles) as well as other electrophiles (e.g.,
      hindered/deactivated/heterocyclic aryl iodides, an aryl bromide, an activated
      aryl chloride, alkenyl halides, and an alkynyl bromide) serve as suitable
      partners. Photoinduced C-N bond formation can be achieved at room temperature
      using a common procedure with an inexpensive catalyst (CuI) that does not require
      a ligand coadditive and is tolerant of moisture and a variety of functional
      groups. 

PMID- 23968564
TI  - Refactoring the silent spectinabilin gene cluster using a plug-and-play scaffold.
AB  - Natural products (secondary metabolites) are a rich source of compounds with
      important biological activities. Eliciting pathway expression is always
      challenging but extremely important in natural product discovery because an
      individual pathway is tightly controlled through a unique regulation mechanism
      and hence often remains silent under the routine culturing conditions. To
      overcome the drawbacks of the traditional approaches that lack general
      applicability, we developed a simple synthetic biology approach that decouples
      pathway expression from complex native regulations. Briefly, the entire silent
      biosynthetic pathway is refactored using a plug-and-play scaffold and a set of
      heterologous promoters that are functional in a heterologous host under the
      target culturing condition. Using this strategy, we successfully awakened the
      silent spectinabilin pathway from Streptomyces orinoci. This strategy bypasses
      the traditional laborious processes to elicit pathway expression and represents a
      new platform for discovering novel natural products.

PMID- 23968566
TI  - Idiopathic basal ganglia calcifications: an atypical presentation of PKAN.
AB  - BACKGROUND: We report a patient with pantothenate kinase-associated
      neurodegeneration presenting as idiopathic basal ganglia calcifications,
      previously known as Fahr's disease. METHODS: A teenage girl presented with slowly
      progressive dystonia. Her brain magnetic resonance imaging scan revealed T1 and
      T2 hypointensities in both globus pallidi, and no eye-of-the-tiger sign. Computed
      tomography showed dense globus pallidi calcifications. Metabolic evaluation was
      negative. The patient was diagnosed with idiopathic basal ganglia calcifications,
      a poorly understood syndrome of unknown cause. Whole exome sequencing was
      performed. RESULTS: The patient was found to have two mutations in the
      pantothenate kinase 2 (PANK2) gene that have been previously associated with
      pantothenate kinase-associated neurodegeneration: a paternally inherited p.G521R
      and maternally inherited p.T528M. No deleterious changes were identified in genes
      associated with idiopathic basal ganglia calcifications or dystonia. CONCLUSIONS:
      Pantothenate kinase-associated neurodegeneration should be considered in patients
      with idiopathic basal ganglia calcifications, especially when findings are
      confined to the globus pallidus.

PMID- 23968567
TI  - Varicella-induced diaphragmatic flutter in a 12-year-old girl.

PMID- 23968568
TI  - Positive persistent visual symptoms (visual snow) presenting as a migraine
      variant in a 12-year-old girl.
AB  - BACKGROUND: Migraine is a common neurological disorder affecting children, in
      which the headache is often preceded or accompanied by a complex of neurological
      symptoms known as an aura. Persistent visual symptoms are rare, with typical
      visual aura sometimes being poorly distinguished from other visual disturbances.
      METHODS: We describe the case of a 12-year-old girl who has experienced
      persistent, constant symptoms throughout the visual fields of white, bright,
      jagged spots and black and white flashes with sparkles and dots since May 2010.
      She also has palinopsia, squiggles, and photophobia. The child's drawing of her
      visual symptoms helps illustrate the case and illuminate her ordeal. RESULTS: The
      child's visual symptoms have so far been resistant to pharmacological therapy.
      CONCLUSION: Further insight is needed into this debilitating condition to allow
      effective management in the pediatric population.

PMID- 23968569
TI  - Potassium bromide for treatment of malignant migrating partial seizures in
      infancy.
AB  - BACKGROUND: The syndrome of malignant migrating partial seizures in infancy is a
      rare epileptic syndrome with a devastating course characterized by early onset of
      continuous pharmacoresistent multifocal seizures arising from multiple
      independent sites of both hemispheres with unknown etiology. PATIENT: A 2-month
      old boy with the characteristic clinical and electroencephalograph pattern of
      migrating partial seizures in infancy was treated with potassium bromide. His
      seizures were unresponsive to the conventional and new generation antiepileptic
      drugs. RESULTS: The seizure frequency was reduced markedly with potassium
      bromide. CONCLUSIONS: Potassium bromide, an old antiepileptic drug, is useful in
      the treatment of malignant migrating partial seizures in infancy.

PMID- 23968570
TI  - Getting the skinny on thick filament regulation in cardiac muscle biology and
      disease.
AB  - Thin (actin) filament accessory proteins are thought to be the regulatory force
      for muscle contraction in cardiac muscle; however, compelling new evidence
      suggests that thick (myosin) filament regulatory proteins are emerging as having
      independent and important roles in regulating cardiac muscle contraction. Key to
      these new findings is a growing body of evidence that point to an influential
      and, more recently, direct role for ventricular myosin light chain-2 (MLC2v)
      phosphorylation in regulating cardiac muscle contraction, function, and disease.
      This includes the discovery and characterization of a cardiac-specific myosin
      light chain kinase capable of phosphorylating MLC2v as well as a myosin
      phosphatase that dephosphorylates MLC2v in the heart, which provides added
      mechanistic insights on MLC2v regulation within cardiac muscle. Here, we review
      evidence for an emerging and critical role for MLC2v phosphorylation in
      regulating cardiac myosin cycling kinetics, function, and disease, based on
      recent studies performed in genetic mouse models and humans. We further provide
      new perspectives on future avenues for targeting these pathways as therapies in
      alleviating cardiac disease. 

PMID- 23968571
TI  - Loss-of-SIRT1 function during vascular ageing: hyperphosphorylation mediated by
      cyclin-dependent kinase 5.
AB  - The longevity regulator SIRT1 is an enzyme catalyzing the deacetylation of
      protein substrates, in turn modulating their biological functions. In endothelial
      cells, downregulation of SIRT1 evokes cellular senescence. In aged arteries,
      SIRT1 expression and activity is blunted, which contributes to the development of
      atherosclerosis and abnormal vascular responses. A recent study suggests that
      cyclin-dependent kinase 5 (CDK5) is responsible for the phosphorylation of SIRT1
      at the serine 47 residue. This modification blocks the anti-senescence activity
      of SIRT1 and plays a critical role in the loss-of-SIRT1 function during vascular
      ageing. Thus, by inhibiting CDK5, SIRT1 function can be improved, in turn
      preventing the development of atherosclerosis and slowing down the process of
      vascular ageing. 

PMID- 23968572
TI  - Vaccination with heat-shocked mononuclear cells as a strategy for treating
      neurodegenerative disorders driven by microglial inflammation.
AB  - Naturally occurring T regulatory cells targeting epitopes derived from various
      heat shock proteins escape thymic negative selection and can be activated by
      vaccination with heat shock proteins; hence, vaccination with such proteins has
      exerted favorable effects on rodent models of autoimmune disorders. A more
      elegant way to achieve such vaccination, first evaluated clinically by Al-Harbi
      in the early 1990s, is to subject mononuclear cells to survivable heat shock ex
      vivo, incubate them at physiological temperature for a further 24-48 h, and then
      inject them subcutaneously; anecdotally, beneficial effects were observed with
      this strategy in a wide range of autoimmune and inflammatory conditions. There is
      growing evidence that M1-activated microglia play a primary or secondary role in
      the pathogenesis of numerous neurodegenerative diseases, as well as in major
      depression. T regulatory cells, by polarizing microglial toward a reparative M2
      phenotype, have the potential to aid control of such disorders. It would be
      appropriate to test the heat-shocked mononuclear cell vaccination strategy in
      animal models of neurodegeneration and major depression, and to evaluate this
      approach clinically if such studies yield encouraging results.

PMID- 23968573
TI  - Postoperative irrigation with bisphosphonates may reduce the recurrence of giant
      cell tumor of bone.
AB  - Giant cell tumor of bone (GCTB) is a common benign bone tumor characterized by
      local osteolysis and high proclivity for recurrence. Surgical excision is the
      preferred treatment. However, simple wide resection may cause functional and
      cosmetic deformities of the skeleton. Currently, intralesional curettage with
      adjuvant therapy is a popular treatment. Bisphosphonates are recommended as an
      effective adjuvant treatment, and their antitumor effects have been proved in
      laboratory studies. During clinical treatment, intravenous and peroral
      administration of bisphosphonates has been attempted and has been successful in
      reducing the tumor recurrence rate. However, the use of bisphosphonates in GCTB
      adjuvant therapy requires additional study. Irrigation is a classic method for
      focal clearance after surgery. Therefore, we hypothesize that postoperative
      irrigation with bisphosphonates may be a safe and effective treatment for GCTB.
      The efficacy and safety of this method are worthy of further investigation. 

PMID- 23968574
TI  - Apelin could reduce risk of contrast-induced nephropathy in patients with
      congestive heart failure.
AB  - Compared to the normal population, patients with congestive heart failure are at
      higher risk for contrast-induced nephropathy. A variety of interventions are
      suggested to reduce the risk for contrast-induced nephropathy. Unfortunately
      results of none of current protective treatments are satisfactory. Apelin a
      vasodilator adipocytokine, positively inotropic agent, and free radical scavenger
      has been recently introduced. It has been shown that endogenous apelin levels are
      decreased in patients with congestive heart failure. Two major mechanisms have
      been suggested for pathophysiology of contrast induced nephropathy including
      reactive oxygen species production and impaired renal perfusion due to
      vasoconstriction. Pretreatment with recombinant apelin (exogenous apelin-13),
      could compensate decreased endogenous apelin serum levels of congestive heart
      failure patients. Its antioxidant and cell-protective properties, decrease
      nephrotoxicity of contrast agent; additionally impaired renal perfusion due to
      malfunction of cardiac pump will refurbish, because of positively inotropic
      property of apelin plus its vasodilatation effect in renal arteries. We believe
      that the triangle of increased contractility, decreased vascular resistance and
      decreased contrast agent nephrotoxicity could significantly reduce risk of
      contrast-induced nephropathy in patients with congestive heart failure. 

PMID- 23968575
TI  - Direct measurements of rate constants for the reactions of CH3 radicals with
      C2H6, C2H4, and C2H2 at high temperatures.
AB  - The shock tube technique has been used to study the reactions CH3 + C2H6 -> C2H4
      + CH4 + H (1), CH3 + C2H4 -> Products + H (2), and CH3 + C2H2 -> Products + H
      (3). Biacetyl, (CH3CO)2, was used as a clean high temperature thermal source for
      CH3-radicals for all the three reactions studied in this work. For reaction 1,
      the experiments span a T-range of 1153 K <= T <= 1297 K, at P ~ 0.4 bar. The
      experiments on reaction 2 cover a T-range of 1176 K <= T <= 1366 K, at P ~ 1.0
      bar, and those on reaction 3 a T-range of 1127 K <= T <= 1346 K, at P ~ 1.0 bar.
      Reflected shock tube experiments performed on reactions 1-3, monitored the
      formation of H-atoms with H-atom Atomic Resonance Absorption Spectrometric
      (ARAS). Fits to the H-atom temporal profiles using an assembled kinetics model
      were used to make determinations for k1, k2, and k3. In the case of C2H6, the
      measurements of [H]-atoms were used to derive direct high-temperature rate
      constants, k1, that can be represented by the Arrhenius equation k1(T) = 5.41 *
      10(-12) exp(-6043 K/T) cm(3) molecules(-1) s(-1) (1153 K <= T <= 1297 K) for the
      only bimolecular process that occurs, H-atom abstraction. TST calculations based
      on ab initio properties calculated at the CCSD(T)/CBS//M06-2X/cc-pVTZ level of
      theory show excellent agreement, within +/-20%, of the measured rate constants.
      For the reaction of CH3 with C2H4, the present rate constant results, k2', refer
      to the sum of rate constants, k(2b) + k(2c), from two competing processes,
      addition-elimination, and the direct abstraction CH3 + C2H4 -> C3H6 + H (2b) and
      CH3 + C2H4 -> C2H2 + H + CH4 (2c). Experimental rate constants for k2' can be
      represented by the Arrhenius equation k2'(T) = 2.18 * 10(-10) exp(-11830 K/T)
      cm(3) molecules(-1) s(-1) (1176 K <= T <= 1366 K). The present results are in
      excellent agreement with recent theoretical predictions. The present study
      provides the only direct measurement for the high-temperature rate constants for
      these channels. Lastly, measurements of H-atoms from the reaction of CH3 with
      C2H2 provided direct unambiguous determinations of the rate constant for the
      dominant process under the present experimental conditions, the addition
      elimination, CH3 + C2H2 -> p-C3H4 + H (3b). Experimental rate constants for k(3b)
      can be represented by the Arrhenius equation k(3b)(T) = 5.16 * 10(-13) exp(-3852
      K/T) cm(3) molecules(-1) s(-1) (1127 K <= T <= 1346 K). The present
      determinations for k(3b) represent the only direct measurements for this reaction
      and are also in good agreement with recent theoretical predictions. The present
      experimental k(3b) values were also used to derive rate constants, k(-3b), for
      the more extensively studied back-process, the reaction of H-atoms with propyne.
      The best fit Arrhenius equation, combining the presently derived k(-3b) values
      with a recent experimental determination for k(-3b), can be represented by k(
      3b)(T) = 3.87 * 10(-11) exp(-1313 K/T) cm(3) molecules(-1) s(-1) (870 K <= T <=
      1346 K). The present studies represent a novel implementation of the sensitive H
      ARAS technique to measure rate constants for poorly characterized and difficult
      to isolate "slow" CH3-radical reactions with stable C2 hydrocarbons.

PMID- 23968576
TI  - Novel Kv1.3 blockers for immunosuppression: WO2012155199.
AB  - A recent patent application from Bionomics/Merck Serono describes novel compounds
      as blockers of the voltage-gated Kv1.3 ion channel. The blockade of this channel
      shows great promise as a new therapeutic target for the treatment of autoimmune
      disorders such as multiple sclerosis, psoriasis, diabetes and rheumatoid
      arthritis. The generic claim of this patent refers to a new chemotype of Kv1.3
      blockers based on an amide core with potent IC50's which are potentially within
      the nanomolar range. This article briefly reviews the chemistry and biology found
      in the patent and compares it with previous discoveries in the field. 

PMID- 23968577
TI  - Hydrodynamic cavitation as a novel approach for delignification of wheat straw
      for paper manufacturing.
AB  - The present work deals with application of hydrodynamic cavitation for
      intensification of delignification of wheat straw as an essential step in the
      paper manufacturing process. Wheat straw was first treated with potassium
      hydroxide (KOH) for 48 h and subsequently alkali treated wheat straw was
      subjected to hydrodynamic cavitation. Hydrodynamic cavitation reactor used in the
      work is basically a stator and rotor assembly, where the rotor is provided with
      indentations and cavitational events are expected to occur on the surface of
      rotor as well as within the indentations. It has been observed that treatment of
      alkali treated wheat straw in hydrodynamic cavitation reactor for 10-15 min
      increases the tensile index of the synthesized paper sheets to about 50-55%,
      which is sufficient for paper board manufacture. The final mechanical properties
      of the paper can be effectively managed by controlling the processing parameters
      as well as the cavitational parameters. It has also been established that
      hydrodynamic cavitation proves to be an effective method over other standard
      digestion techniques of delignification in terms of electrical energy
      requirements as well as the required time for processing. Overall, the work is
      first of its kind application of hydrodynamic cavitation for enhancing the
      effectiveness of delignification and presents novel results of significant
      interest to the paper and pulp industry opening an entirely new area of
      application of cavitational reactors.

PMID- 23968578
TI  - Wastewater treatment using hybrid treatment schemes based on cavitation and
      Fenton chemistry: a review.
AB  - Advanced oxidation processes such as cavitation and Fenton chemistry have shown
      considerable promise for wastewater treatment applications due to the ease of
      operation and simple reactor design. In this review, hybrid methods based on
      cavitation coupled with Fenton process for the treatment of wastewater have been
      discussed. The basics of individual processes (Acoustic cavitation, Hydrodynamic
      cavitation, Fenton chemistry) have been discussed initially highlighting the need
      for combined processes. The different types of reactors used for the combined
      processes have been discussed with some recommendations for large scale
      operation. The effects of important operating parameters such as solution
      temperature, initial pH, initial pollutant concentration and Fenton's reagent
      dosage have been discussed with guidelines for selection of optimum parameters.
      The optimization of power density is necessary for ultrasonic processes (US) and
      combined processes (US/Fenton) whereas the inlet pressure needs to be optimized
      in the case of Hydrodynamic cavitation (HC) based processes. An overview of
      different pollutants degraded under optimized conditions using HC/Fenton and
      US/Fenton process with comparison with individual processes have been presented.
      It has been observed that the main mechanism for the synergy of the combined
      process depends on the generation of additional hydroxyl radicals and its proper
      utilization for the degradation of the pollutant, which is strongly dependent on
      the loading of hydrogen peroxide. Overall, efficient wastewater treatment with
      high degree of energy efficiency can be achieved using combined process operating
      under optimized conditions, as compared to the individual process. 

PMID- 23968579
TI  - Capsaicin-induced metabolic and cardiovascular autonomic improvement in an animal
      model of the metabolic syndrome.
AB  - The metabolic syndrome (MetS) is associated with an increased risk of cardiac
      mortality, as it is characterised by the clustering of multiple cardiovascular
      risk factors. Studies have shown that capsaicin (red pepper) may be useful as a
      nutraceutical, ameliorating metabolic profile and cardiovascular function. The
      aim of the present study was to investigate the cardiovascular and metabolic
      effects of orally administered capsaicin in rats with the MetS. Neonate
      spontaneously hypertensive rats were injected with monosodium glutamate and
      subjected to one of the following three treatments by oral administration for 14
      d, between 27 and 30 weeks: low-dose capsaicin (CAP05, n 18, synthetic capsaicin
      powder diluted in a vehicle (10 % ethyl alcohol) plus 0.5 mg/kg body weight (BW)
      of capsaicin); high-dose capsaicin (CAP1, n 19, synthetic capsaicin powder
      diluted in a vehicle (10 % ethyl alcohol) plus 1 mg/kg BW of capsaicin); control
      (C, n 18, vehicle). Lee's index, lipid/metabolic profile, and cardiovascular
      parameters with the rats being conscious, including arterial pressure (AP) and
      heart rate (HR) variability, as well as aortic wall thickness (haematoxylin and
      eosin staining) and CD68 (cluster of differentiation 68) antibody levels
      (monocyte/macrophage immunostaining) were evaluated. Weight, Lee's index, and
      lipid and metabolic parameters, as well as AP and HR and aortic wall thickness,
      were similar between the groups. Capsaicin determined HR variability improvement
      (16.0 (sem 9.0), 31.0 (sem 28.2) and 31.3 (sem 19.0) ms2 for the C, CAP05 and
      CAP1 groups, respectively, P= 0.003), increased vascular sympathetic drive (low
      frequency component of systolic AP variability: 3.3 (sem 2.8), 8.2 (sem 7.7) and
      12.1 (sem 8.8) mmHg2 for the C, CAP05 and CAP1 groups, respectively, P< 0.001)
      and increased alpha-index (spontaneous baroreflex sensitivity). The present data
      show that capsaicin did not improve lipid and glucose abnormalities in rats with
      the MetS. However, beneficial cardiovascular effects were observed with this
      nutraceutical. 

PMID- 23968580
TI  - Developmental programming in skeletal muscle in response to overnourishment in
      the immediate postnatal life in rats.
AB  - Overnourishment during the suckling period [small litter (SL)] results in the
      development of adult-onset obesity. To investigate the mechanisms that underlie
      the development of insulin resistance in the skeletal muscle of young and adult
      female SL rats, the litter size was reduced to 3 female pups/dam (SL) while the
      control litter had 12 pups/dam from the postnatal Day 3 until Day 21. Protein
      content, mRNA expression and methylation status of the promoter region of key
      components in the insulin signaling pathway were determined in the skeletal
      muscle of SL rats. Overnutrition during the suckling period resulted in increased
      body weight gains, hyperphagia and adult-onset obesity as well as increased
      levels of serum insulin, glucose and leptin in SL rats. No differences in the
      expression of total protein as well as tyrosine phosphorylation of insulin
      receptor beta and glucose transporter 4 (Glut4) were observed in skeletal muscle
      between two groups at both ages. A significant decrease of total insulin receptor
      substrate 1 (IRS-1) and an increase in serine phosphorylation of IRS-1 were
      observed in skeletal muscle from adult SL rats. Hypermethylation of specific
      cytidyl-3',5'phospho-guanylyl (CpG) dinucleotides in the proximal promoter region
      was observed for the Irs1 and Glut4 genes, which correlated with the reduction in
      Irs1 and Glut4 mRNA levels in skeletal muscle of adult SL rats. Our results
      suggest that epigenetic modifications of the key genes involved in the insulin
      signaling pathway in skeletal muscle could result in the development of insulin
      resistance in SL female rats. 

PMID- 23968581
TI  - 3,3'-diindolylmethane rapidly and selectively inhibits hepatocyte growth factor/c
      Met signaling in breast cancer cells.
AB  - 3,3'-Diindolylmethane (DIM), an indole derivative from vegetables of the Brassica
      genus, has antiproliferative activity in breast cancer cells. Part of this
      activity is thought to be due to DIM inhibition of Akt signaling, but an upstream
      mechanism of DIM-induced Akt inhibition has not been described. The goals of this
      study were to investigate the kinetics of inhibition of Akt by physiologically
      relevant concentrations of DIM and to identify an upstream factor that mediates
      this effect. Here we report that DIM (5-25 MUM) inhibited Akt activation from 30
      min to 24h in tumorigenic MDA-MB-231 cells but did not inhibit Akt activation in
      non-tumorigenic preneoplastic MCF10AT cells. DIM inhibited hepatocyte growth
      factor (HGF)-induced Akt activation by up to 46%, cell migration by 66% and cell
      proliferation by up to 54%, but did not inhibit induction of Akt by epidermal
      growth factor or insulin-like growth factor-1. DIM decreased phosphorylation of
      the HGF receptor, c-Met, at tyrosines 1234 and 1235, indicating decreased
      activation of the receptor. This decrease was reversed by pretreatment with
      inhibitors of p38 or calcineurin. Our results demonstrate the important role of
      HGF and c-Met in DIM's anti-proliferative effect on breast cancer cells and
      suggest that DIM could have preventive or clinical value as an inhibitor of c-Met
      signaling.

PMID- 23968582
TI  - Assessment of the needs of caregivers of stroke patients at state-owned acute
      care hospitals in southern Vietnam, 2011.
AB  - INTRODUCTION: Care for stroke patients has improved steadily in southern Vietnam.
      Medical treatments such as thrombolytic therapy have been implemented at several
      hospitals, and stroke-care units composed of a team of various health
      professionals have been created. However, little attention has been focused on
      providing support to caregivers of stroke patients. This study aimed to
      characterize the caregivers of stroke patients who were treated in state-owned
      acute-care hospitals and to learn about their needs when patients are discharged.
      Such information can be used to enhance the caregiver's support system. METHODS:
      We used questionnaires to conduct a descriptive study in 2011 at a state-owned
      acute-care hospital in southern Vietnam. We recruited study participants from
      among caregivers of stroke patients who had been informed of their hospital
      discharge date. We assessed 8 caregiver characteristics, and caregiver
      participants selected their needs from the survey's list of 15 possible needs. We
      analyzed the data by using the independent sample t test and logistic regression.
      RESULTS: Of the 93 caregivers who consented to participate, 86 (92.5%) completed
      the survey and indicated their concerns at discharge. The most frequently cited
      need was information on how to prevent stroke recurrence (72, 83.7%), followed by
      which drugs are most effective in preventing a relapse (62, 72.1%), how long
      recovery would take (61, 70.9%), and availability of hospitals in the patient's
      hometown (60, 69.8%). A little over half of caregivers indicated financial
      concerns. A caregiver's need for information on diet for a stroke survivor
      increased with the caregiver's education level. CONCLUSIONS: This study revealed
      several needs among caregivers of stroke survivors in southern Vietnam that are
      similar to those found by studies of caregivers of stroke survivors in high
      income countries. Our findings suggest that comprehensive stroke care that
      includes caregiver education about healthful diets and prevention of stroke
      recurrence is needed at state-owned acute-care hospitals in southern Vietnam.

PMID- 23968583
TI  - Frequent mental distress, chronic conditions, and adverse health behaviors in the
      Behavioral Risk Factor Surveillance Survey, Jordan, 2007.
AB  - INTRODUCTION: Recent evidence indicates that chronic diseases and mental illness
      are associated. In the Middle Eastern country of Jordan, chronic diseases and
      frequent mental distress (FMD) are increasing; however, the capacity for mental
      health care is limited. The objective of this study was to determine the
      association between FMD, chronic conditions, and adverse health behaviors in
      Jordan. METHODS: The third cycle of the Jordan Behavioral Risk Factor
      Surveillance Survey (2007) served as the data source for this study. The sample
      consisted of 3,612 noninstitutionalized Jordanian adults aged 18 years or older.
      Logistic regression was used to obtain odds ratios for the association between
      chronic conditions, health behaviors, and FMD adjusted for age, sex, marital
      status, education, income, and employment. RESULTS: In the adjusted models,
      people with hypertension (adjusted odds ratio [AOR], 2.0; 95% confidence interval
      [CI], 1.6-2.7), high cholesterol (AOR, 2.3; 95% CI, 1.6-3.2), diabetes (AOR, 1.6;
      95% CI, 1.1-2.4), and asthma (AOR, 2.2; 95% CI, 1.5-3.1) and smokers (AOR, 1.5;
      95% CI, 1.1-2.0) were more likely to have FMD than people without each of these
      conditions. Adults who reported vigorous physical activity were less likely to
      have FMD (AOR, 0.6; 95% CI, 0.4-0.9) than their less active counterparts.
      CONCLUSIONS: In Jordan, FMD was associated with several chronic conditions. As a
      result, we suggest additional research to examine the complex relationship
      between FMD and chronic conditions. More doctors in the primary health care
      system should be trained in mental health.

PMID- 23968584
TI  - An effective community-academic partnership to extend the reach of screenings for
      fall risk.
AB  - Older adults should be screened for fall risk annually. Community providers
      (people without formal medical training who work with older adults in senior
      centers or aging services) may be a viable group to expand the reach of
      screenings. Our community-academic partnership developed a program to increase
      and assess fall risk screenings by community providers. Community sites hosted
      training workshops and screening events. Community screenings were well attended
      and received by providers and older adults. With administrative support from the
      regional fall prevention coalition and technical support from academia, community
      providers screened 161 older adults from a broad geographic area. Twenty-one
      community providers completed the training. Knowledge and confidence surveys
      demonstrated improvements before and after training (P<.001). Skills assessments
      demonstrated mastery of most skills, but some providers required additional
      training. Provider feedback indicated screening procedures were complex. Future
      projects will examine this model using simplified screening procedures.

PMID- 23968585
TI  - Are physical education policies working? A snapshot from San Francisco, 2011.
AB  - INTRODUCTION: School physical education (PE) has been identified as a critical
      public health tool to increase physical activity among youths. We sought to
      objectively assess compliance with PE quantity mandates and quality
      recommendations in a large urban California school district. METHODS: We
      collected PE schedules and systematically observed PE lessons (n=154) in 20
      elementary, 4 middle, and 4 high schools from February through May 2011. RESULTS:
      On the basis of schools' master schedules, 83% of elementary schools met the
      California state mandate of 100 PE minutes per week. Teachers' actual schedules
      indicated that 20% of schools met the mandate, and observation showed that only
      5% were in compliance. All middle and high schools met the mandated 200 minutes
      per week. On average, classes at all school levels met the recommended 50% of PE
      lesson time in moderate-to-vigorous physical activity. No teacher- or school
      level factors significantly predicted PE quantity, but credentialed elementary PE
      teachers spent more time building students' motor skills. CONCLUSIONS: Our
      results suggest that current national estimates of PE, which are based on
      schools' self-report, overestimate the amount of PE provided in elementary
      schools. Although more than half of PE class time was spent in moderate-to
      vigorous physical activity, total physical activity in elementary schools from PE
      is minimal and may do little to contribute to students' overall health.

PMID- 23968586
TI  - Diagnosis of skin lesions caused by Dermanyssus gallinae in five patients.

PMID- 23968587
TI  - Cathepsin L silencing enhances arsenic trioxide mediated in vitro cytotoxicity
      and apoptosis in glioblastoma U87MG spheroids.
AB  - Despite improved treatment options, glioblastoma multiforme (GBM) remains the
      most aggressive brain tumour with the shortest post-diagnostic survival. Arsenite
      (As2O3) is already being used in the treatment of acute promyelocytic leukaemia
      (APL), yet its effects on GBM have not been evaluated in detail. In U87MG cell
      monolayers, we have previously shown that arsenite cytotoxicity significantly
      increases upon transient inhibition of lysosomal protease Cathepsin L (CatL). As
      multicellular spheroids more closely represent in vivo tumours, we aimed to
      evaluate the impact of permanent CatL silencing on arsenite treatment in U87MG
      spheroids. CatL was stably silenced using shRNA expression plasmid packed
      lentiviruses. By using metabolic- and cell viability assays, we demonstrated that
      long-term CatL silencing significantly increased arsenite cytotoxicity in U87MG
      spheroids. Silenced CatL also increased arsenite-mediated apoptosis in spheroids
      via elevated p53 expression, Bax/Bcl2 ratio and caspase 3/7 activity, though with
      lower efficacy than in monolayers. Arsenite cytotoxicity was enhanced by lower
      CatL activity, since similar cytotoxicity increase was also observed using the
      novel CatL inhibitor AT094. The results have significant translational impact,
      since stable CatL silencing would enable the application of lower systemic doses
      of arsenite to achieve the desired cytotoxic effects on GBMs in vivo.

PMID- 23968588
TI  - Intermittent hypoxia induces the proliferation of rat vascular smooth muscle cell
      with the increases in epidermal growth factor family and erbB2 receptor.
AB  - Obstructive sleep apnea is characterized by intermittent hypoxia (IH), and
      associated with cardiovascular diseases, such as stroke and heart failure. These
      cardiovascular diseases have a relation to atherosclerosis marked by the
      proliferation of vascular smooth muscle cells (VSMCs). In this study, we
      investigated the influence of IH on cultured rat aortic smooth muscle cell
      (RASMC). The proliferation of RASMC was significantly increased by IH without
      changing the level of apoptosis. In order to see what induces RASMC
      proliferation, we investigated the influence of normoxia (N)-, IH- and sustained
      hypoxia (SH)-treated cell conditioned media on RASMC proliferation. IH-treated
      cell conditioned medium significantly increased RASMC proliferation compared with
      N-treated cell conditioned medium, but SH-treated cell conditioned medium did
      not. We next investigated the epidermal growth factor (EGF) family as autocrine
      growth factors. Among the EGF family, we found significant increases in mRNAs for
      epiregulin (ER), amphiregulin (AR) and neuregulin-1 (NRG1) in IH-treated cells
      and mature ER in IH-treated cell conditioned medium. We next investigated the
      changes in erbB family receptors that are receptors for ER, AR and NRG1, and
      found that erbB2 receptor mRNA and protein expressions were increased by IH, but
      not by SH. Phosphorylation of erbB2 receptor at Tyr-1248 that mediates
      intracellular signaling for several physiological effects including cell
      proliferation was increased by IH, but not by SH. In addition, inhibitor for
      erbB2 receptor suppressed IH-induced cell proliferation. These results provide
      the first demonstration that IH induces VSMC proliferation, and suggest that EGF
      family, such as ER, AR and NRG1, and erbB2 receptor could be involved in the IH
      induced VSMC proliferation.

PMID- 23968590
TI  - Olfactory cues increase avoidance behavior and induce Fos expression in the
      amygdala, hippocampus and prefrontal cortex of socially defeated mice.
AB  - Genes and proteins of the Fos family are used as markers of neuronal activity and
      can be modulated by stress. This study investigated whether social defeat (SD) or
      exposure to an olfactory cue associated with the SD experience activated Fos and
      FosB/DeltaFosB (DeltaFosB) expression in brain regions implicated in the
      development of post-traumatic stress disorder. Mice exposed to acute SD showed
      more Fos positive cells in the basolateral amygdala (BLA), CA1 of the hippocampus
      and the medial prefrontal cortex (mPFC) 1h after SD, and had greater expression
      of the more persistent FosB/DeltaFosB protein in the BLA 24 h after SD compared
      to controls. Mice exposed to an olfactory cue 24 h or 7 days after SD had higher
      levels of Fos expression in all three regions 1h after exposure to the cue, and
      displayed increased avoidance behavior compared to controls. While the avoidance
      response dissipated with time (less at 7 day vs 24 h after social defeat), Fos
      expression in the mPFC and CA1 in response to an olfactory cue was greater at 7
      days relative to 24 h after social defeat. The results suggest additional
      processing of the cue-stress association and may provide further support for a
      role of the mPFC in fear inhibition. These findings may have implications for
      brain regions and circuitry involved in the avoidance of cues associated with a
      stressful event that may lead to context-dependent adaptive or maladaptive
      behavior.

PMID- 23968589
TI  - Opioid self-administration results in cell-type specific adaptations of striatal
      medium spiny neurons.
AB  - Medium-sized spiny neurons (MSNs), the predominant neuronal population of the
      striatum, are an integral component of the many cortical and limbic pathways
      associated with reward-related behaviors. A differential role of the D1 receptor
      enriched (D1) MSNs of the striatonigral direct pathway, as compared with the D2
      receptor-enriched (D2) MSNs of the striatopallidal indirect pathway, in mediating
      the addictive behaviors associated with cocaine is beginning to emerge. However,
      whether opioids, well-known analgesics with euphoric properties, similarly induce
      dissociable signaling adaptations in these neurons remains unclear. Transgenic
      mice expressing green fluorescent protein (GFP)-labeled D1 or D2 neurons were
      implanted with intravenous jugular catheters. Mice learned to self-administer
      0.1mg/kg/infusion of the opioid remifentanil during 2h sessions over 13
      contiguous days. Thereafter, the electrophysiological properties of D1- and D2
      MSNs in the shell region of the nucleus accumbens (NAc) were assessed. We found
      that prior opioid exposure did not alter the basic membrane properties nor the
      kinetics or amplitude of miniature excitatory postsynaptic currents (mEPSCs).
      However, when challenged with the mu opioid receptor (MUOR) agonist DAMGO, the
      characteristic inhibitory profile of this receptor was altered. DAMGO inhibited
      the frequency of mEPSCs in D1-MSNs from control mice receiving saline and in D2
      MSNs from mice exposed to remifentanil or saline, but this inhibitory profile was
      reduced in D1-MSNs from mice receiving remifentanil. Remifentanil exposure also
      altered the probability of glutamate release onto D1-, but not D2-MSNs. Together
      these results suggest a D1-pathway specific effect associated with the
      acquisition of opioid-seeking behaviors. 

PMID- 23968591
TI  - Long-term treadmill exercise inhibits the progression of Alzheimer's disease-like
      neuropathology in the hippocampus of APP/PS1 transgenic mice.
AB  - Previously our study has demonstrated that long-term treadmill exercise improved
      cognitive deficit in APP/PS1 transgenic mice of Alzheimer's disease (AD)
      paralleled by enhanced long-term potentiation (LTP). The present study was
      undertaken to further investigate whether the treadmill running could inhibit the
      progression of Alzheimer's disease (AD)-like neuropathology in hippocampus of the
      APP/PS1 mouse models of AD, and to define a potential molecular mechanism
      underlying the exercise-induced reduction in AD-like neuropathology. Five months
      of treadmill exercise resulted in a robust reduction in beta-amyloid (Abeta)
      deposition and tau phosphorylation in the hippocampus of APP/PS1 mice. This was
      accompanied by a significant decrease in APP phosphorylation and PS1 expression.
      We also observed GSK3, rather than CDK5, was inhibited by treadmill exercise.
      These results indicate that treadmill exercise is sufficient to inhibit the
      progression of AD-like neuropathology in the hippocampus of APP/PS1 transgenic
      mouse model, and may mediate APP processing in favor of reduced Abeta deposition.
      In addition, we demonstrate that treadmill exercise attenuates AD-like
      neuropathology in AD transgenic mice via a GSK3 dependent signaling pathway. 

PMID- 23968592
TI  - The neuroprotective role and mechanisms of TERT in neurons with oxygen-glucose
      deprivation.
AB  - Telomerase reverse transcriptase (TERT) is reported to protect neurons from
      apoptosis induced by various stresses including hypoxia-ischemia (HI). However,
      the mechanisms by which TERT exerts its anti-apoptotic role in neurons with HI
      injury remain unclear. In this study, we examined the protective role and
      explored the possible mechanisms of TERT in neurons with HI injury in vitro.
      Primary cultured neurons were exposed to oxygen and glucose deprivation (OGD) for
      3h followed by reperfusion to mimic HI injury in vivo. Plasmids containing TERT
      antisense, sense nucleotides, or mock were transduced into neurons at 48h before
      OGD. Expression and distribution of TERT were measured by immunofluorescence
      labeling and western blot. The expression of cleaved caspase 3 (CC3), Bcl-2 and
      Bax were detected by western blot. Neuronal apoptosis was measured with terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). The
      mitochondrial reactive oxygen species (ROS) were measured by MitoSOX Red
      staining. Fluorescent probe JC-1 was used to measure the mitochondrial membrane
      potential (DeltaPsim). We found that TERT expression increased at 8h and peaked
      at 24h in neurons after OGD. CC3 expression and neuronal apoptosis were induced
      and peaked at 24h after OGD. TERT inhibition significantly increased CC3
      expression and neuronal apoptosis after OGD treatment. Additionally, TERT
      inhibition decreased the expression ratio of Bcl-2/Bax, and enhanced ROS
      production and DeltaPsim dissipation after OGD. These data suggest that TERT
      plays a neuroprotective role via anti-apoptosis in neurons after OGD. The
      underlying mechanisms may be associated with regulating Bcl-2/Bax expression
      ratio, attenuating ROS generation, and increasing mitochondrial membrane
      potential.

PMID- 23968593
TI  - Training on motor and visual spatial learning tasks in early adulthood produces
      large changes in dendritic organization of prefrontal cortex and nucleus
      accumbens in rats given nicotine prenatally.
AB  - Experience-dependent plasticity is an ongoing process that can be observed and
      measured at multiple levels. The first goal of this study was to examine the
      effects of prenatal nicotine on the performance of rats in three behavioral tasks
      (elevated plus maze (EPM), Morris water task (MWT), and Whishaw tray reaching).
      The second goal of this experiment sought to examine changes in dendritic
      organization following exposure to the behavioral training paradigm and/or low
      doses of prenatal nicotine. Female Long-Evans rats were administered daily
      injections of nicotine for the duration of pregnancy and their pups underwent a
      regimen of behavioral training in early adulthood (EPM, MWT, and Whishaw tray
      reaching). All offspring exposed to nicotine prenatally exhibited substantial
      increases in anxiety. Male offspring also showed increased efficiency in the
      Whishaw tray-reaching task and performed differently than the other groups in the
      probe trial of the MWT. Using Golgi-Cox staining we examined the dendritic
      organization of the medial and orbital prefrontal cortex as well as the nucleus
      accumbens. Participation in the behavioral training paradigm was associated with
      dramatic reorganization of dendritic morphology and spine density in all brain
      regions examined. Although both treatments (behavior training and prenatal
      nicotine exposure) markedly altered dendritic organization, the effects of the
      behavioral experience were much larger than those of the prenatal drug exposure,
      and in some cases interacted with the drug effects. 

PMID- 23968594
TI  - Ligation-independent cloning and self-cleaving intein as a tool for high
      throughput protein purification.
AB  - The rapid production of purified recombinant proteins has become increasingly
      important for countless applications. Many purification methods involve
      expression of target proteins in fusion to purification tags, which often must be
      removed from the target proteins after purification. Recently, engineered inteins
      have been used to create convenient self-cleaving tags for tag removal. Although
      intein methods can greatly simplify protein purification, commercially available
      expression vectors still rely on conventional restriction/ligation cloning
      methods for target gene insertion. We have streamlined this process by
      introducing Ligation-Independent Cloning (LIC) capability to our intein
      expression plasmids, which provides a simple method for constructing self
      cleaving tag-target gene fusions. In this work, we demonstrate efficient gene
      insertion via this system, as well as target protein expression and purification
      consistent with previously reported results. Through this newly developed system,
      arbitrary protein genes can be rapidly incorporated into self-cleaving tag
      expression vectors, and their products purified using convenient platform
      methods. 

PMID- 23968595
TI  - The compatibility heuristic in non-categorical hypothetical reasoning: inferences
      between conditionals and disjunctions.
AB  - A new theory explains how people make hypothetical inferences from a premise
      consistent with several alternatives to a conclusion consistent with several
      alternatives. The key proposal is that people rely on a heuristic that identifies
      compatible possibilities. It is tested in 7 experiments that examine inferences
      between conditionals and disjunctions. Participants accepted inferences between
      conditionals and inclusive disjunctions when a compatible possibility was
      immediately available, in their binary judgments that a conclusion followed or
      not (Experiment 1a) and ternary judgments that included it was not possible to
      know (Experiment 1b). The compatibility effect was amplified when compatible
      possibilities were more readily available, e.g., for 'A only if B' conditionals
      (Experiment 2). It was eliminated when compatible possibilities were not
      available, e.g., for 'if and only if A B' bi-conditionals and exclusive
      disjunctions (Experiment 3). The compatibility heuristic occurs even for
      inferences based on implicit negation e.g., 'A or B, therefore if C D'
      (Experiment 4), and between universals 'All A's are B's' and disjunctions
      (Experiment 5a) and universals and conditionals (Experiment 5b). The implications
      of the results for alternative theories of the cognitive processes underlying
      hypothetical deductions are discussed. 

PMID- 23968596
TI  - Validity and reliability of the Japanese version of the family needs survey.
AB  - Early intervention and disability services in Japan historically have focused on
      supporting the individual with a disability, with only secondary attention to
      family needs and priorities. Since the Basic Law for Persons with Disabilities
      was codified in 2011, the Japanese government has been responsible for supporting
      families with members who have disabilities. To assess the needs of these
      families, we evaluated the reliability and validity of the Family Needs Survey
      (FNS), initially developed in 1988 (Bailey & Simeonsson), to determine its
      usefulness for programs providing services for Japanese families who have a child
      with a disability. The FNS is a practical tool to assess family needs and is
      already used across many different cultures and populations. To evaluate the
      reliability and validity of the FNS, we conducted an anonymous survey with a self
      administered questionnaire at 6 treatment and education institutions, 3 medical
      institutions mainly for children with disabilities, and 39 special needs schools
      in the Osaka area. We analyzed 1171 parents' survey responses: 452 fathers and
      719 mothers of children with disabilities aged 0-15 years old who answered all
      items on the Japanese version of the FNS. Another survey was administered to 130
      specialists who work with children with disabilities to assess the content
      validity of the Japanese version of the FNS. We verified the factor structure,
      content validity, and reliability of the Japanese version of the FNS as an
      assessment tool with 34 items among four factors that were based on the same
      items in the original FNS. The assessment could be used for families with school
      age children as well as younger children, in contrast to the original version,
      which is not appropriate for school-age children. We also confirmed that it could
      be used without regard to type or degree of disability. 

PMID- 23968597
TI  - A new dietary strategy for long-term treatment of the metabolic syndrome is
      compared with the American Heart Association (AHA) guidelines: the MEtabolic
      Syndrome REduction in NAvarra (RESMENA) project.
AB  - The long-term effects of dietary strategies designed to combat the metabolic
      syndrome (MetS) remain unknown. The present study evaluated the effectiveness of
      a new dietary strategy based on macronutrient distribution, antioxidant capacity
      and meal frequency (MEtabolic Syndrome REduction in NAvarra (RESMENA) diet) for
      the treatment of the MetS when compared with the American Heart Association
      guidelines, used as Control. Subjects with the MetS (fifty-two men and forty-one
      women, age 49 (se 1) years, BMI 36.11 (se 0.5) kg/m2) were randomly assigned to
      one of two dietary groups. After a 2-month nutritional-learning intervention
      period, during which a nutritional assessment was made for the participants every
      15 d, a 4-month self-control period began. No significant differences were found
      between the groups concerning anthropometry, but only the RESMENA group exhibited
      a significant decrease in body weight ( - 1.7%; P= 0.018), BMI ( - 1.7%; P=
      0.019), waist circumference ( - 1.8%; P= 0.021), waist:hip ratio ( - 1.4%; P=
      0.035) and android fat mass ( - 6.9%; P= 0.008). The RESMENA group exhibited a
      significant decrease in alanine aminotransferase and aspartate aminotransferase
      (AST) concentrations ( - 26.8%; P= 0.008 and - 14.0%; P= 0.018, respectively),
      while the Control group exhibited a significant increase in glucose (7.9%; P=
      0.011), AST (11.3%; P= 0.045) and uric acid (9.0%; P< 0.001) concentrations. LDL
      cholesterol (LDL-C) concentrations were increased (Control group: 34.4%; P< 0.001
      and RESMENA group: 33.8%; P< 0.001), but interestingly so were the LDL-C:apoB
      ratio (Control group: 28.7%; P< 0.001, RESMENA group: 17.1%; P= 0.009) and HDL
      cholesterol concentrations (Control group: 21.1%; P< 0.001, RESMENA group: 8.7;
      P= 0.001). Fibre was the dietary component that most contributed to the
      improvement of anthropometry, while body-weight loss explained changes in some
      biochemical markers. In conclusion, the RESMENA diet is a good long-term dietary
      treatment for the MetS.

PMID- 23968598
TI  - Quinto Tiberio Angelerio and new measures for controlling plague in 16th-century
      Alghero, Sardinia.
AB  - Plague, a zoonotic disease caused by the bacterium Yersinia pestis, has been
      responsible for at least 3 pandemics. During 1582-1583, a plague outbreak
      devastated the seaport of Alghero in Sardinia. By analyzing contemporary medical
      texts and local documentation, we uncovered the pivotal role played by the
      Protomedicus of Alghero, Quinto Tiberio Angelerio (1532-1617), in controlling the
      epidemic. Angelerio imposed rules and antiepidemic measures new to the 16th
      century sanitary system of Sardinia. Those measures undoubtedly spared the
      surrounding districts from the spread of the contagion. Angelerio seems to have
      been an extremely successful public health officer in the history of plague
      epidemics in Sardinia.

PMID- 23968599
TI  - Breaking news in health policy and the power of social media.

PMID- 23968600
TI  - Canadian pharmacare: looking back, looking forward.
AB  - Despite Canadians' pride in medicare and the values underpinning it, the system
      is conspicuously incomplete. Universal public health insurance in Canada ends as
      soon as a patient is handed a prescription to fill; yet prescription drugs are
      the second largest component of health system costs. We look back at key moments
      in Canadian healthcare history that shaped our pharmacare system - or lack
      thereof. We look forward to changes in demography and technology that will
      increase the need for pharmacare reform in the near future. We conclude that
      meaningful public engagement in pharmacare design may generate the clarity of
      goals and level of political support needed should windows of policy opportunity
      open again. 

PMID- 23968601
TI  - Reforms in Pakistan: decisive times for improving maternal and child health.
AB  - Pakistan is a struggling economy with poor maternal and child health indicators
      that have affected attainment of the United Nations Millennium Development Goals
      4 and 5 (under-five child and maternal mortality). Recent health reforms have
      abolished the federal Ministry of Health and devolved administrative and
      financial powers to the provinces. Ideally, devolution tends to simplify a
      healthcare system's management structure and ensure more efficient delivery of
      health services to underserved populations, in this case women and children. In
      this time of transition, it is appropriate to outline prerequisites for the
      efficient management of maternal and child health (MCH) services. This paper
      examines the six building blocks of health systems in order to improve the
      utilization of MCH services in rural Pakistan. The targeted outcomes of recent
      reforms are devolved participatory decision-making regarding distribution of MCH
      related services, improved deployment of the healthcare workforce, prioritization
      of pro-poor strategies for health financing and integration of various health
      information systems. Given this window of opportunity, the provinces need to
      guarantee fairness and equity through their stewardship of the healthcare system
      so as to protect vulnerable mothers and their children, especially in rural,
      remote and disadvantaged areas of Pakistan. 

PMID- 23968602
TI  - Mining the management literature for insights into implementing evidence-based
      change in healthcare.
AB  - OBJECTIVE: We synthesized the management and health literatures for insights into
      implementing evidence-based change in healthcare drawn from industry-specific
      data. Because change principles based on evidence often fail to be translated
      into organizational practice or policy, we sought studies at the nexus of
      organizational change and knowledge translation. METHODS: We reviewed five top
      management journals to identify an initial pool of 3,091 studies, which yielded a
      final sample of 100 studies. Data were abstracted, verified by the original
      authors and revised before entry into a database. We employed a systematic
      narrative synthesis approach using words and text to distill data and explain
      relationships. We categorized studies by varying levels of relevance for
      knowledge translation as (1) primary, direct; (2) intermediate; and (3)
      secondary, indirect. We also identified recurring categories of change-related
      organizational factors. The current analysis examines these factors in studies of
      primary relevance to knowledge translation, which we also coded for intervention
      readiness to reflect how readily change can be implemented. Preliminary RESULTS
      AND CONCLUSIONS: Results centred on five change-related categories: Tailoring the
      Intervention Message; Institutional Links/Social Networks; Training; Quality of
      Work Relationships; and Fit to Organization. In particular, networks across
      institutional and individual levels appeared as prominent pathways for changing
      healthcare organizations. Power dynamics, positive social relations and team
      structures also played key roles in implementing change and translating it into
      practice. We analyzed journals in which first authors of these studies typically
      publish, and found evidence that management and health sciences remain divided.
      Bridging these disciplines through research syntheses promises a wealth of
      evidence and insights, well worth mining in the search for change that works in
      healthcare transformation.

PMID- 23968603
TI  - The effect of social capital on the use of general practitioners: a comparison of
      immigrants and non-immigrants in Ontario.
AB  - Social capital, a resource arising from the social interaction among individuals,
      may be a determinant of medical care use. This study explored the interaction
      between community- and individual-level social capital and immigrant status on
      the propensity and frequency of physician visits. The results showed that
      community social capital, as measured by the Petris Social Capital Index, was not
      significant in any of the analyses. However, a sense of belonging to the local
      community tended to decrease the number of doctor visits made by immigrants,
      while tangible social support increased and affection decreased the frequency of
      GP consultations by non-immigrants. Further research is required to determine
      which types of social capital affect utilization of different health services.
      These findings also highlight the importance of being aware of potential
      interactions between the formal and informal components of the healthcare system.

PMID- 23968604
TI  - The visible politics of the privatization debate in Quebec.
AB  - This paper analyzes the debates surrounding the privatization of health services
      financing in Quebec. The objective is to clarify policy-making processes with
      regard to this important issue and, more generally, to provide a realistic
      understanding of health-related policy processes in Canada. The analysis is based
      on a large and continuous sample of mass media and National Assembly debates on
      the question during the four-and-a-half years following the Chaoulli ruling of
      the Supreme Court of Canada. These data are used to test four hypotheses about
      relationships among the types of political actors involved, their policy
      preferences, the rhetoric they use and the anticipated policy effects they
      assert. The results are applied to a discussion of questions about the factors
      that influence the effectiveness of political communication. 

PMID- 23968605
TI  - What are wait times to see a specialist? an analysis of 26,942 referrals in
      southwestern Ontario.
AB  - BACKGROUND: Reducing wait times is a key goal of Canadian health planners and
      policy makers. Using data from the EMRs of 23 family physicians across
      southwestern Ontario, we present data on wait times to see a specialist, and
      evaluate these data for equity. METHODS: Cross-sectional analysis of EMR database
      of 29,303 patients and 544,398 encounters from October 2005 to July 2010. Wait
      time was calculated as the difference between the specialist appointment date and
      the family physician's referral date. Multilevel regression analysis was used to
      assess equity in waiting times. RESULTS: The median wait was 53 days, with female
      patients having a slightly longer wait than males (55 vs. 51 days), and younger
      patients (median = 45 days) having the shortest wait. Differences were noted
      among practices, with a range of 42-63 days. The longest waits were for
      neurosurgery (median = 103 days) and the shortest for paediatricians (median = 28
      days). There was no correlation between wait times and income, but significant
      associations were noted for patient age, sex and referral urgency.
      INTERPRETATION: This is the first study to present data on actual wait times for
      a broad array of specialists over a five-year period. There is variation among
      specialties and by practice, and further research is needed to understand reasons
      for these. From a policy perspective, there is equity in wait times in
      southwestern Ontario, as waits are not correlated with SES. Future work should
      model the patient-, physician- and contextual-level factors that determine
      specialist wait times.

PMID- 23968606
TI  - The role of community-based care capacity in shaping risk of long-term care
      facility placement.
AB  - OBJECTIVES: Across the developed world, wait lists for facility-based long-term
      care (LTC) beds continue to grow. Wait lists are primarily driven by the needs of
      aging populations (demand-side factors). Less attention has been given to system
      capacity to provide community alternatives to LTC (supply-side factors). We
      examine the role of both demand- and supply-side factors by comparing the
      characteristics of individuals who have been assessed and deemed eligible for LTC
      in urban and rural/underserviced parts of northwestern Ontario, Canada. METHODS:
      Home care assessment data were analyzed for all individuals waiting for LTC in
      northwestern Ontario as of March 2008 (n=858). For the analysis, the sample was
      separated into urban and rural groups to account for geographical differences in
      wait list location. Characteristics between these two groups were compared.
      RESULTS: Individuals on LTC wait lists in the rural areas were significantly less
      impaired in activities of daily living and cognition than their counterparts in
      the urban area. However, in both areas, impairments in lighter-care activities
      appeared to be a key wait list driver, and few people had an informal caregiver
      living in the home. CONCLUSIONS: Our data suggest that LTC wait lists reflect, at
      least to some extent, insufficient community capacity, not just need for LTC.

PMID- 23968607
TI  - Risk factors for increased severity of paediatric medication administration
      errors.
AB  - Patients' risks from medication errors are widely acknowledged. Yet not all
      errors, if they occur, have the same risks for severe consequences. Facing
      resource constraints, policy makers could prioritize factors having the greatest
      severe-outcome risks. This study assists such prioritization by identifying work
      related risk factors most clearly associated with more severe consequences. Data
      from three Canadian paediatric centres were collected, without identifiers, on
      actual or potential errors that occurred. Three hundred seventy-two errors were
      reported, with outcome severities ranging from time delays up to fatalities. Four
      factors correlated significantly with increased risk for more severe outcomes:
      insufficient training; overtime; precepting a student; and off-service patient.
      Factors' impacts on severity also vary with error class: for wrong-time errors,
      the factors precepting a student or working overtime significantly increase
      severe-outcomes risk. For other types, caring for an off-service patient has
      greatest severity risk. To expand such research, better standardization is needed
      for categorizing outcome severities. 

PMID- 23968608
TI  - An unusual co-occurrence of Langerhans cell histiocytosis and Rosai-Dorfman
      disease: report of a case and review of the literature.
AB  - BACKGROUND: The co-occurrence of Langerhans cell histiocytosis (LCH; disorder
      characterized by proliferation of Langerhans cells) and Rosai-Dorfman disease
      (RDD; histiocytic entity that is one of the non-Langerhans cell diseases) is
      extremely rare and raises several questions regarding the nature of the diseases.
      METHODS: We describe a 10-year-old boy who presented with a 3-month history of
      right scalp swelling. Clinical, pathological, and imaging evaluation disclosed
      multiple LCH of bone and cutaneous RDD. RESULTS: After initiating prednisone and
      vinblastine therapy, the patient developed an asymptomatic diffuse papular
      eruption. Biopsy revealed cutaneous RDD. Treatment was continued with a good
      response of bone LCH and significant amelioration of the cutaneous findings.
      CONCLUSIONS: Co-occurrence of LCH and RDD is a rare phenomenon. Various
      explanations, including the role of chemotherapy, are suggested based on our and
      several previously reported cases.

PMID- 23968609
TI  - Chikungunya virus infection, Brazzaville, Republic of Congo, 2011.

PMID- 23968610
TI  - An ounce of prevention.

PMID- 23968611
TI  - Putting some mustard into economic growth.
AB  - On September 27, 2012, the University of Toronto launched the Fraser Mustard
      Institute for Human Development - an appropriate recognition of an extraordinary
      individual. Fraser was a keen student of the science of human development and,
      most particularly, of early child development (ECD). He was also a powerful and
      tireless advocate for translating science into action. His institute must do
      both. Action is needed also because 25% of Canadians lack the competencies to
      function effectively in a modern economy. Other countries do much better. Facing
      a low-growth future, we cannot afford to waste this untapped potential. Although
      Prime Minister Harper's personal ideology has no place for ECD, the Mustard
      Institute can help keep the flame alive. 

PMID- 23968612
TI  - Disproportionate organizational injustice: a close look at facilities exempted
      from indoor smoking laws in Canada.
AB  - Federal and provincial legislation bans smoking in indoor public spaces and
      workplaces, yet exemptions exist for residential facilities such as nursing homes
      and addiction treatment centres. In relying on ventilated smoking rooms, however,
      these organizations are failing to protect the health of their employees and
      clients. Increased use of risk messages regarding the harms of second- and third
      hand smoke, together with enhanced nicotine replacement therapies for smokers,
      would rectify this disproportionate injustice. Such an approach must also
      recognize and counteract the efforts of the tobacco industry to block total
      indoor smoking bans. 

PMID- 23968613
TI  - Public payments to physicians in Ontario adjusted for overhead costs.
AB  - We used data collected in the 2010 National Physician Survey and public payment
      data published in the Institute for Clinical and Evaluative Sciences report
      Payments to Ontario Physicians from Ministry of Health and Long-Term Care Sources
      1992/93 to 2009/10 to estimate 2009/2010 net physician income from public
      payments for Ontario physicians by specialty. Incorporating overhead
      substantially affects estimates of physician income and changes relative
      position. For example, ophthalmologists were ranked second when only public
      payments were considered but eighth when overhead was included. Conversely,
      hospital-based specialties such as anaesthesia, radiation oncology and emergency
      medicine rank significantly higher after overhead is included. 

PMID- 23968614
TI  - Making evidence on health policy issues accessible to the media.
AB  - The media shape consumer expectations and interpretations of health
      interventions, influencing how people think about their need for care and the
      sustainability of the system. EvidenceNetwork.ca is a non-partisan, web-based
      project funded by the Canadian Institutes of Health Research and the Manitoba
      Health Research Council to make the latest evidence on controversial health
      policy issues available to the media. This website links journalists with health
      policy experts. We publish opinion pieces on current health policy issues in both
      French and English. We track who follows and uses the EvidenceNetwork.ca website
      and monitor the impact of our efforts. 

PMID- 23968615
TI  - MotherFirst: developing a maternal mental health strategy in Saskatchewan.
AB  - Up to 20% of women experience maternal mental health problems, but most
      jurisdictions lack policy for prevention, identification and treatment. To
      address this gap, a multi-stakeholder working group formed in Saskatchewan,
      Canada. As a result, the MotherFirst project emerged to create policies to
      improve the mental healthcare of mothers and to increase public and professional
      awareness. This paper critically analyzes the project using a policy cycle
      framework that can inform similar policy development. It explores the strengths
      of diverse partnerships, relationship building and public awareness campaigns,
      and the challenges that were encountered in the decision-making and
      implementation stages. 

PMID- 23968616
TI  - Developing primary care: the contribution of primary care research networks.
AB  - The performance of Canada's primary care sector remains lacklustre relative to
      other wealthy industrialized countries, and it has been suggested that a lack of
      investment in research and evaluation may be a cause. One approach to improving
      and sustaining primary care research is through research networks. Over the past
      few years, significant investments have begun to be made in developing primary
      care networks in Canada. While Canadian experience in this area is relatively
      new, in the United Kingdom primary care research networks were first established
      in the 1980s. Initially developed at a local level, these have more recently been
      incorporated into large-scale national networks. This paper reviews the UK
      experience and highlights potential lessons for the development of networks in
      Canada. 

PMID- 23968618
TI  - Metrics survey of industry-sponsored clinical trials in Canada and comparator
      jurisdictions between 2005 and 2010.
AB  - Industry-sponsored clinical trials play a key role in the development of
      therapies. This survey suggests that between 2005 and 2010, research-based
      pharmaceutical firms worldwide initiated fewer trials and recruited fewer
      subjects annually. In contrast, at the country level, the clinical trial activity
      of such firms increased in emerging countries and in Japan. Canada's trend in the
      number of new trials followed that of the global industry, but the trend in new
      sites and newly recruited subjects fell below the global rate. Informal
      comparisons point to potential issues for Canada in such areas as site capacity,
      cost per subject and time to first subject-in. When compared to certain Western
      European countries and the United States, Canada remained well positioned on a
      number of metrics. Nonetheless, Canada faces mounting challenges from both
      traditional locations and emerging countries and may require coordinated efforts
      to remain a place of choice to conduct trials. 

PMID- 23968617
TI  - Inequity in access to guideline-recommended colorectal cancer treatment in Nova
      Scotia, Canada.
AB  - Cancer continues to be one of the heaviest burdens of disease in Canada, and
      assessing potential inequities in access to cancer care may serve as a barometer
      of the health of Canadian health systems. This study tackled three limitations of
      the current literature by clearly differentiating between inequality and
      inequity, by assessing inequity in receipt of care and wait times for care, and
      by taking advantage of inequity indices to enhance comparability of inequities
      between studies and populations. We measured income-, age-, sex- and distance
      related inequities among colorectal cancer (CRC) patients in Nova Scotia by
      accounting for clinical guidelines and patient need. Results reveal statistically
      significant inequity in access to chemotherapy and radiotherapy for CRC by age,
      sex and distance, but not income. This study demonstrates the importance of
      carefully examining inequity in access to cancer care and highlights one method
      to report and compare inequities with conceptual clarity. 

PMID- 23968619
TI  - Variations in patients' assessment of chronic illness care across organizational
      models of primary health care: a multilevel cohort analysis.
AB  - PURPOSE: To measure patients' assessment of chronic illness care and its
      variation across primary healthcare (PHC) models. METHODS: We recruited 776
      patients with diabetes, heart failure, arthritis or chronic obstructive pulmonary
      disease from 33 PHC clinics. Face-to-face interviews, followed by a telephone
      interview at 12 months, were conducted using the Patient Assessment of Chronic
      Illness Care (PACIC). Multilevel regression was used in the analysis. RESULTS:
      The mean PACIC score was low at 2.5 on a scale of 1 to 5. PACIC scores were
      highest among patients affiliated with family medicine groups (mean, 2.78) and
      lowest for contact models (mean, 2.35). Patients with arthritis and older persons
      generally reported a lower assessment of chronic care. CONCLUSION: Family
      medicine groups represent an integrated model of PHC associated with higher
      levels of achievement in chronic care. Variations across PHC organizations
      suggest that some models are more appropriate for improving management of chronic
      illness.

PMID- 23968621
TI  - Chorea and tick-borne encephalitis, Poland.

PMID- 23968622
TI  - Learning from rural health innovation.

PMID- 23968620
TI  - Comparison of the American-European Consensus Group Sjogren's syndrome
      classification criteria to newly proposed American College of Rheumatology
      criteria in a large, carefully characterised sicca cohort.
AB  - OBJECTIVE: To compare the performance of the American-European Consensus Group
      (AECG) and the newly proposed American College of Rheumatology (ACR)
      classification criteria for Sjogren's Syndrome (SS) in a well-characterised sicca
      cohort, given ongoing efforts to resolve discrepancies and weaknesses in the
      systems. METHODS: In a multidisciplinary clinic for the evaluation of sicca, we
      assessed features of salivary and lacrimal gland dysfunction and autoimmunity as
      defined by tests of both AECG and ACR criteria in 646 participants. Global gene
      expression profiles were compared in a subset of 180 participants. RESULTS:
      Application of the AECG and ACR criteria resulted in classification of 279 and
      268 participants with SS, respectively. Both criteria were met by 244
      participants (81%). In 26 of the 35 AECG+/ACR participants, the minor salivary
      gland biopsy focal score was >=1 (74%), while nine had positive anti-Ro/La (26%).
      There were 24 AECG-/ACR+ who met ACR criteria mainly due to differences in the
      scoring of corneal staining. All patients with SS, regardless of classification,
      had similar gene expression profiles, which were distinct from the healthy
      controls. CONCLUSIONS: The two sets of classification criteria yield concordant
      results in the majority of cases and gene expression profiling suggests that
      patients meeting either set of criteria are more similar to other SS participants
      than to healthy controls. Thus, there is no clear evidence for increased value of
      the new ACR criteria over the old AECG criteria from the clinical or biological
      perspective. It is our contention, supported by this report, that improvements in
      diagnostic acumen will require a more fundamental understanding of the pathogenic
      mechanisms than is at present available.

PMID- 23968623
TI  - Rural health services: finding the light at the end of the tunnel.
AB  - Many rural communities across canada are facing challenges to the sustainability
      of core emergency and acute care health services, primarily due to problems with
      medical and nursing staffing. Data related to service efficacy and effectiveness
      are not well organized. Most of Canada still relies on reporting by large
      geopolitical areas (local health areas) that do not always relate natural
      catchment population outcomes to community hospital services. Re-organizing rural
      health services' outcome reporting by the characteristics of geographically
      defined catchment populations would facilitate better planning, systemic quality
      improvement and stronger continuing professional development for health
      professionals. It may also serve to inform the transformation of core health
      services in larger communities.

PMID- 23968624
TI  - Money left on the table: generic drug prices in Canada.
AB  - BACKGROUND: Generic drugs are a major cost-saving opportunity for patients and
      drug plans. While almost every province has reduced generic drug prices, we have
      no information on whether these new prices are internationally competitive.
      Therefore, I compared Canadian prices to those in two other countries. METHODS: I
      used 2009 data from the IMS Brogan Canadian CompuScript and PharmaStat databases
      and studied the 100 most frequently dispensed generic products in Ontario, which
      has Canada's lowest generic prices. I compared these prices to those in public
      drug programs in the United States and New Zealand that use tendering. Using
      these alternative prices, I calculated the potential savings in Ontario. RESULTS:
      Of the top 100 generic products, 82 were listed on an international formulary. In
      90% of cases, generic products were less expensive in other countries. If Ontario
      had obtained the lowest comparator price for these products, the annual public
      sector and overall drug expenditure savings would have been $129 million and $245
      million, respectively. Further, the province could have publicly paid for all
      these generic drugs - both public and private - and saved $87 million compared to
      current public sector expenditures. DISCUSSION: Even after recent reforms,
      generic drug prices in Canada remain high by international standards. I found
      that if Ontario had obtained commonly used generic drugs at international best
      prices, the province could have publicly paid for all generic drugs and lowered
      annual expenditures by nearly a quarter-billion dollars.

PMID- 23968625
TI  - Development of a rural health framework: implications for program service
      planning and delivery.
AB  - PURPOSE: To describe the development and application of an evidence-based rural
      health framework to guide rural health program, policy and service planning.
      METHODS: A literature review of rural health programs, focusing on health
      promotion, chronic disease prevention and population health, was conducted using
      several bibliographic databases. FINDINGS: Thirty papers met the criteria for
      review, describing chronic disease interventions and public health policies in
      rural settings. Twenty-one papers demonstrated effective intervention programs
      and highlighted potential good practices for rural health programs, which were
      used to define key elements of a rural health framework. CONCLUSIONS: The rural
      health framework was applied to an influenza immunization program to demonstrate
      its utility in assisting public health providers to increase uptake of the
      vaccine. This rural health framework provides an opportunity for program planners
      to reflect on the key issues facing rural communities to ensure the development
      of policies and strategies that will prudently and effectively meet population
      health needs.

PMID- 23968626
TI  - Evaluation of physician return-for-service agreements in Newfoundland and
      Labrador.
AB  - INTRODUCTION: Despite the widespread use of physician return-for-service (RFS)
      programs in Canada, few have been evaluated. We examined two types of RFS
      agreements (Family Medicine Bursary and Special Funded Residency Position) and
      (a) describe the proportion of RFS physicians who complete their service
      obligation and identify the predictors of completion and (b) compare the
      retention of RFS physicians to that of non-RFS physicians. METHODS: Using
      administrative data on physicians with RFS agreements in Newfoundland and
      Labrador (NL), Memorial University's Postgraduate Medical Education Office and
      the Physician and Medical Practice Database, we calculated the proportion of RFS
      physicians (1997-2009) who fulfilled their service obligation and also identified
      predictors of completion. We then followed to 2010 a cohort of physicians who
      started practice in NL between 2000 and 2005 to compare the retention of RFS and
      non-RFS physicians. RESULTS: Ninety-six (71.6%) of 134 RFS physicians fulfilled
      the service obligation in full. Physicians who held Special Funding Residency
      Position RFS agreements were 11.1 times less likely (95% CI: 4.0-33.3) to
      complete their service commitment than physicians who held Family Medicine
      Bursary RFS agreements. In the cohort of 60 RFS and 67 non-RFS physicians, 16.9%
      of RFS versus 41.8% of non-RFS physicians left NL by 2010 (p=0.004). RFS
      physicians were 3.22 times less likely (95% CI: 1.41-7.14) than non-RFS
      physicians to leave the province. Four years after starting practice, roughly 90%
      of RFS versus 60% of non-RFS physicians remained in NL; after 10 years, 70% of
      RFS versus 60% of non-RFS physicians remained (p=0.006). CONCLUSION: The RFS
      program improves the retention of physicians in NL. Using RFS tied to bursaries
      rather than residency positions may increase service completion and retention
      rates.

PMID- 23968627
TI  - An overview of practice facilitation programs in Canada: current perspectives and
      future directions.
AB  - Practice facilitation has proven to be effective in improving the quality of
      primary care. A practice facilitator is a health professional, usually external
      to the practice, who regularly visits the practice to provide support in change
      management that targets improvements in the delivery of care. Our environmental
      scan shows that several initiatives across Canada utilize practice facilitation
      as a quality improvement method; however, many are conducted in isolation as
      there is a lack of coordinated effort, knowledge translation and dissemination in
      this field across the country. We recommend that investments be made in capacity
      building, knowledge exchange and facilitator training, and that partnership
      building be considered a priority in this field.

PMID- 23968628
TI  - The effect of cigarette plain packaging on individuals' health warning recall.
AB  - PURPOSE: To examine the extent to which increasingly plainer packaging might
      increase recall of health warnings. DESIGN: A 4 (pack ID levels) x 2 (smoking
      status: smokers and non-smokers) between-subjects design in which participants
      were randomly assigned to view one package. SAMPLE: Two hundred and twenty
      students from three universities in Nova Scotia, Canada, participated in the
      survey. MEASURES: Participants were asked to recall the health warning on their
      package. ANALYSIS: A sequential binary logistic regression test to examine
      whether plain packaging and/or smoking status affects health warning recall.
      RESULTS: The odds of recalling the correct health warnings were significantly
      higher for the two plainest packages relative to the original package. The odds
      of recalling the correct health warning were also higher for non-smokers relative
      to smokers. CONCLUSIONS: The results provide compelling evidence that health
      warnings on plain packages can be more easily recalled.

PMID- 23968629
TI  - What, if anything, does amenable mortality tell us about regional health system
      performance?
AB  - OBJECTIVES: Amenable mortality is proposed as a health system performance
      measure, and has been used in comparisons across countries and socio-economic
      strata. We assess its utility as a health region-level indicator in Canada.
      APPROACH: We classified all deaths in British Columbia from 2002 to 2009 using
      two common definitions of amenable mortality. Counts and standardized rates were
      calculated for 16 health regions. To assess reliability, sensitivity and
      validity, we compared rates across regions and over time, and examined
      correlations with premature and all-cause mortality. RESULTS: Of the 238,849
      deaths in the study period, 6.6% or 13.7% were classified as amenable (depending
      on the definition used). Rates were stable or falling in more populated regions,
      but unstable with large confidence intervals elsewhere. Correlation with overall
      mortality was strong. CONCLUSION: Though amenable mortality is appealing as a
      feasible, understandable indicator, we question whether it is appropriate for
      comparisons at a subprovincial level.

PMID- 23968630
TI  - Improving collaboration between public health and family health teams in Ontario.
AB  - OBJECTIVES: To identify and explore areas where responsibilities may overlap
      between family health teams (FHTs) and public health units (PHUs); to identify
      facilitators or barriers to collaboration; and to identify priority areas for
      increased collaboration. DESIGN AND CONTEXT: Cross-sectional mixed-methods study
      of FHTs and PHUs in Ontario, Canada, consisting of a postal survey, key informant
      interviews and a roundtable meeting. RESULTS: The survey response rate was 46%.
      Direct client-based services such as giving immunizations, promoting prenatal
      health and nutrition, and counselling related to smoking cessation were
      identified as the top three areas of perceived overlap. The greatest interest in
      collaboration was expressed in the areas of emergency planning and preparedness,
      immunization, and prenatal health and nutrition. Good communication with a clear
      understanding of roles and functions was the most important facilitator, and lack
      of resources and absence of a clear provincial mandate and direction to
      collaborate were identified as significant barriers. CONCLUSIONS: Small, simple
      client-based projects of interest to both kinds of organization would be the best
      way to move forward in the short term. Improving communication between FHTs and
      PHUs, understanding of roles and functions, the use of shared or interoperable
      information systems and greater clarity from government on the ways in which
      these two key sectors of the healthcare system are intended to work together were
      identified as important for the success of increased collaboration.

PMID- 23968632
TI  - The rewards of volunteering.

PMID- 23968631
TI  - Alaria alata Infection in European mink.

PMID- 23968633
TI  - "It doesn't have to be this way".
AB  - Clyde Hertzman's sudden and untimely death was a terrible blow to those who knew
      him. It was also a major loss to health research and policy in canada and well
      beyond. He was an outstanding public academic, at the top of his intellectual
      game. here i attempt a highly selective and personal account of how he developed
      the conceptual framework that he called "the whole enchilada," of the social
      context influencing both biological and behavioural development from earliest
      infancy. From these roots spring our life trajectories, evolving social gradients
      of more--or less--successful experience at each life stage. the international
      performance of a society reflects the sum of these trajectories. Canada could do
      much better, but not in Harperland.

PMID- 23968634
TI  - How to summarize a 6,000-word paper in a six-minute video clip.
AB  - As part of our research team's knowledge transfer and exchange (KTE) efforts, we
      created a six-minute video clip that summarizes, in plain language, a scientific
      paper that describes why and how three teams of academic entrepreneurs developed
      new health technologies. Recognizing that video-based KTE strategies can be a
      valuable tool for health services and policy researchers, this paper explains the
      constraints and sources of inspiration that shaped our video production process.
      Aiming to provide practical guidance, we describe the steps and tools that we
      used to identify, refine and package the key content of the scientific paper into
      an original video format.

PMID- 23968635
TI  - The rising prevalence of asthma: true increase, diagnostic exchange or diagnostic
      accuracy?
AB  - In the midst of frequent reports about "the asthma epidemic," results from a
      number of studies by the manitoba centre for health policy have shown stable or
      decreasing prevalence of an overall indicator of respiratory diseases which
      includes asthma. To resolve these apparently contrary findings, we conducted a
      time trend analysis using administrative data. results revealed significant
      potential for diagnostic exchange: asthma prevalence increased, but that of
      bronchitis decreased.

PMID- 23968636
TI  - Wait time from primary to specialty care: a trend analysis from Edmonton, Canada.
AB  - Medical wait time is a top health policy issue in canada. reliable data on the
      referral wait time from primary to specialty care are limited. Existing data on
      referral wait times are generally self-reported by specialists. In 2008, the
      edmonton north primary care network (PCN) developed a centralized referral
      program, including a specialist database that contains information on
      specialists' referral requirements, forms and protocols, and has the capability
      of tracking referrals that the PCN makes on behalf of its family physicians to
      specialty care. We performed a trend analysis of the referral wait time (defined
      as the time from referral by a family physician to an appointment date with a
      specialist) from 2009 to 2011 using the program database (n=33,281 referrals).
      The study provided a unique and comprehensive picture of wait times for 22
      specialties. We identified a decrease in the overall wait time year over year,
      and improvement in the number of referrals that are accepted the first time.
      additionally, specific opportunities for further improvement in referral wait
      time were noted.

PMID- 23968637
TI  - Use of product listing agreements by Canadian provincial drug benefit plans.
AB  - BACKGROUND: Product listing agreements (PLAs) between drug manufacturers and drug
      plans are increasingly common worldwide. Use of PLAs by Canadian provinces has
      not previously been documented. METHODS: We collected data from all provinces on
      funding and PLA use for 25 drugs that were reviewed by the Common Drug Review
      (CDR) in 2010 or 2011 and funded by at least one province as of May 2012. We
      measured correlations between coverage and PLA use, and CDR recommendations and
      PLA use. RESULTS: The number of drugs from our sample funded by provinces ranged
      from three in Prince Edward Island to 21 in Ontario. PLA use ranged from zero in
      Quebec, Prince Edward Island, and Newfoundland and Labrador to 20 in Ontario. The
      correlation between drugs funded and PLAs used by each province was statistically
      significant (r=0.57, p=0.04); excluding Ontario, however, the correlation was not
      significant (r=0.10, p=0.40). There was a stronger correlation between the number
      of provinces funding a drug and the number using PLAs among the subset of drugs
      with negative CDR recommendations (r=0.87, p<0.01) versus those with positive
      recommendations (r=0.52, p=0.03). Of the 12 drugs sampled with a negative CDR
      recommendation, 10 were funded with a PLA in at least one province.
      INTERPRETATION: There is wide interprovincial variation in PLA use and evidence
      that PLAs may be used to fund drugs that are not otherwise cost-effective. If
      global pricing strategies are making PLAs necessary, Canadian governments should
      collaborate to improve the equity, transparency and effectiveness of PLAs across
      provinces.

PMID- 23968638
TI  - System integration and clinical utilization of the Advanced Clinician
      Practitioner in Arthritis Care (ACPAC) Program-Trained Extended Role
      Practitioners in Ontario: a two-year, system-level evaluation.
AB  - BACKGROUND: The Advanced Clinician Practitioner in Arthritis Care (ACPAC) program
      was developed in 2005 to prepare experienced physical and occupational therapists
      to function as extended role practitioners (ERPs) within models of arthritis care
      across Ontario, Canada. PURPOSE: To examine the system-level integration and
      clinical utilization of the ACPAC program-trained ERP. METHOD: A longitudinal
      survey was administered to all ACPAC graduates over a two-year period (n=30).
      RESULTS: The majority of ERPs were physical therapists working in urban settings.
      Family physicians or physician specialists referred the majority of patients. The
      longest median wait time to access ERPs' services was 22 days. Half of the ERPs
      triaged patients, and most of those who did triage (75%) worked under medical
      directives. Approximately half (51.6%) of the patients seen had a diagnosis of
      osteoarthritis, followed by rheumatoid arthritis (14.7%). CONCLUSION:
      Understanding the system-level impact of this unique human resource can help to
      shape healthcare planning and delivery of care.

PMID- 23968639
TI  - Things are not as bad as they seem: physicians' ability to predict their clinical
      practice when a new vaccine becomes available.
AB  - Survey results regarding primary care physicians' likelihood of recommending a
      new vaccine were compared before and after the vaccine was licensed by the Food
      and Drug Administration for three new vaccines: herpes zoster (HZ), human
      papillomavirus (HPV) and rotavirus (RV), using physician networks representative
      of United States physicians. The main purpose of this study was to determine (a)
      how accurately physicians predict their eventual vaccine recommendations and the
      barriers they will experience in delivering the new vaccine and (b) whether
      physicians shift towards more or less strongly recommending a new vaccine from
      pre- to post-licensure. Responses from 284, 152 and 184 physicians were analyzed
      for the three vaccines, respectively. For all vaccines, there was a significant
      association between physicians' pre- and post-licensure recommendations (p<0.05).
      When responses changed from pre- to post-licensure, physicians tended to
      recommend a given vaccine more strongly than they had anticipated pre-licensure.
      Before vaccine availability, physicians tended to predict greater barriers to
      vaccine delivery than they eventually experienced. Surveys are useful for
      predicting physician practices, but may provide a slightly pessimistic view of
      physician adoption of new vaccines. Such data can be helpful in devising
      strategies to encourage vaccine delivery by physicians.

PMID- 23968640
TI  - Meeting the privacy requirements for the development of a multi-centre patient
      registry in Canada: the Rick Hansen Spinal Cord Injury Registry.
AB  - Privacy legislation addresses concerns regarding the privacy of personal
      information; however, its interpretation by research ethics boards has resulted
      in significant challenges to the collection, management, use and disclosure of
      personal health information for multi-centre research studies. This paper
      describes the strategy used to develop the national Rick Hansen Spinal Cord
      Injury Registry (RHSCIR) in accordance with privacy statutes and benchmarked
      against best practices. An analysis of the regional and national privacy
      legislation was conducted to determine the requirements for each of the 31 local
      RHSCIR sites and the national RHSCIR office. A national privacy and security
      framework was created for RHSCIR that includes a governance structure, standard
      operating procedures, training processes, physical and technical security and
      privacy impact assessments. The framework meets a high-water mark in ensuring
      privacy and security of personal health information nationally and may assist in
      the development of other national or international research initiatives. 

PMID- 23968641
TI  - Human papillomavirus multiplex ligation-dependent probe amplification assay for
      the assessment of viral load, integration, and gain of telomerase-related genes
      in cervical malignancies.
AB  - We evaluated the reliability of a novel multiplex ligation-dependent probe
      amplification (MLPA) assay in detecting integration of human papillomavirus (HPV)
      based on the viral E2/E6 copy number ratio in formalin-fixed and paraffin
      embedded cervical lesions. The MLPA results were compared with those of
      amplification of papillomavirus oncogene transcripts for RNA, detection of
      integrated papillomavirus sequences for DNA, and HPV fluorescence in situ
      hybridization (FISH). DNA was isolated from 41 formalin-fixed and paraffin
      embedded HPV-positive cervical lesions (cervical intraepithelial neoplasia grade
      3 lesions, squamous cell carcinomas, and adenocarcinomas) for MLPA analysis. From
      13 matching frozen samples, DNA and RNA were isolated for the detection of
      integrated papillomavirus sequences and/or the amplification of papillomavirus
      oncogene transcripts, respectively. Integrated HPV16, HPV18, or both were
      identified. The MLPA assay detected viral integration in 12 of these 13 cases,
      and episomal copies also were detected in 7 cases. In 20 of the 24 cases with
      exclusive viral integration or episomal viral copies as detected by FISH, MLPA
      confirmed the physical status of the virus. In the cases classified as mixed by
      FISH, the presence of excess episomal copies complicated the recognition of viral
      integration by MLPA. Furthermore, the feasibility of detecting gain of the
      telomerase genes with the HPV MLPA assay was evaluated. The MLPA confirmed the
      FISH data in 12 of 13 cases in which the status of copy number gain for
      telomerase RNA component was known. In conclusion, the HPV MLPA assay can be
      performed on routinely processed cervical lesions for the detection of viral load
      and HPV integration. 

PMID- 23968643
TI  - Sensitive and rapid detection of blaNDM-1 in clinical samples by isothermal cross
      priming amplification.
AB  - A highly sensitive, specific diagnostic assay for detection of bla(NDM-1) based
      on cross priming amplification (CPA) was developed. The sensitivity ranged from
      2.5 to 25 copies per reaction for different clinical samples. The highly and
      sensitive detection of bla(NDM-1) in clinical samples highlighted the potential
      clinical applications of CPA.

PMID- 23968642
TI  - Mechanisms of dopamine transporter regulation in normal and disease states.
AB  - The dopamine (DA) transporter (DAT) controls the spatial and temporal dynamics of
      DA neurotransmission by driving reuptake of extracellular transmitter into
      presynaptic neurons. Many diseases such as depression, bipolar disorder,
      Parkinson's disease (PD), and attention deficit hyperactivity disorder (ADHD) are
      associated with abnormal DA levels, implicating DAT as a factor in their
      etiology. Medications used to treat these disorders and many addictive drugs
      target DAT and enhance dopaminergic signaling by suppressing transmitter
      reuptake. We now understand that the transport and binding properties of DAT are
      regulated by complex and overlapping mechanisms that provide neurons with the
      ability to modulate DA clearance in response to physiological demands. These
      processes are controlled by endogenous signaling pathways and affected by
      exogenous transporter ligands, demonstrating their importance for normal
      neurotransmission, drug abuse, and disease treatments. Increasing evidence
      supports the disruption of these mechanisms in DA disorders, implicating
      dysregulation of transport in disease etiologies and suggesting these processes
      as potential points for therapeutic manipulation of DA availability. 

PMID- 23968644
TI  - A chip-calorimetric approach to the analysis of Ag nanoparticle caused inhibition
      and inactivation of beads-grown bacterial biofilms.
AB  - With the increasing complexity of model systems for the investigation of
      antibacterial effects of nanoparticles, the demands on appropriate analysis
      methods are rising. In case of biofilms grown on small particles, the high
      inhomogeneity of the samples represents a major challenge for traditional biofilm
      analysis. For this purpose, we developed a new calorimetric method which allows
      non-invasive and real-time investigation of the effects of nanoparticles on beads
      grown biofilms which meets the requirements for an increased sample throughput.
      The method employs a newly developed chip calorimeter that is able to detect
      changes in the metabolic activity of biofilm samples within minutes. Using this
      novel device, the antibacterial effect of silver nanoparticles on Pseudomonas
      putida biofilms grown on agarose beads was investigated. The superparamagnetic
      properties of the embedded particles within the agarose beads allow an automated
      sample throughput. Growth inhibition and inactivation effects of silver
      nanoparticles (AgNPs) on biofilm bacteria were quantified by analyzing the
      metabolic heat production rate. As a result, a concentration dependent manner of
      growth inhibition and inactivation was found demonstrating the suitability and
      sensitivity of the methodology. 

PMID- 23968645
TI  - Minimization of chloroplast contamination in 16S rRNA gene pyrosequencing of
      insect herbivore bacterial communities.
AB  - Chloroplast sequence contamination in 16S ribosomal RNA gene (16S) analyses can
      be particularly problematic when sampling microbial communities in plants and
      folivorous arthropods. We previously encountered high levels of plastid
      contamination in herbivorous insect samples when we used the predominant 454
      pyrosequencing 16S methodologies described in the literature. 799F, a primer
      previously found to exclude chloroplast sequences, was modified to enhance its
      efficacy, and we describe, in detail, our methodology throughout amplicon
      pyrosequencing. Thirteen versions of 799F were assessed for the exclusion of
      chloroplast sequences from our samples. We found that a shift in the mismatch
      between 799F and chloroplast 16S resulted in significant reduction of chloroplast
      reads. Our results also indicate that amplifying sequences from environmental
      samples in a two-step PCR process, with the addition of the multiplex identifiers
      and 454 adapters in a second round of PCR, further improved primer specificity.
      Primers that included 3' phosphorothioate bonds, which were designed to block
      primer degradation, did not amplify consistently across samples. The different
      forward primers do not appear to bias the bacterial communities detected. We
      provide a methodological framework for reducing chloroplast reads in high
      throughput sequencing data sets that can be applied to a number of environmental
      samples and sequencing techniques. 

PMID- 23968647
TI  - Comparison of liquid chromatography-tandem mass spectrometry-based targeted
      proteomics and conventional analytical methods for the determination of P
      glycoprotein in human breast cancer cells.
AB  - P-glycoprotein (P-gp) is the most frequently proposed factor for multi-drug
      resistance. It is traditionally measured using antibody-based methods. While
      these techniques can provide relative quantification values for P-gp levels, the
      important information that is usually missing is its amount in the biological
      system. In this study, a novel and advanced liquid chromatography-tandem mass
      spectrometry (LC/MS/MS)-based targeted proteomics assay was developed and
      validated for the determination of P-gp in the breast cancer drug sensitive cell
      line MCF-7/WT and the drug resistant cell line MCF-7/ADR. Three tryptic peptides
      (434STTVQLMQR442, 674GSQAQDR680 and 368IIDNKPSIDSYSK380) can specifically
      represent P-gp. Among these peptides, 434STTVQLMQR442 was selected as the
      surrogate analyte for quantification, and a stable isotope-labeled synthetic
      peptide with the same sequence was used as an internal standard. The calibration
      range was validated from 10 to 1000ng/mL. The intra- and inter-day precisions
      were within 5.9% and 3.7%, respectively. The accuracy for the quality control
      (QC) samples was within 8.0%. Using this assay, the amounts of P-gp were
      accurately quantified as 3.53fg/cell (~2.08*10(-2)amol/cell) in the MCF-7/WT
      cells and 34.5fg/cell (~2.02*10(-1)amol/cell) in the MCF-7/ADR cells. This
      outcome was then compared with those obtained by conventional analytical methods
      including confocal microscopy, western blotting and flow cytometry. The
      comparative results show that not only is the LC/MS/MS-based targeted proteomics
      assay able to monitor the protein levels in a more accurate manner, but the large
      discrepancy observed between the other methods was most likely due to the lack of
      specificity and the semi-quantitative nature of the conventional assays. 

PMID- 23968646
TI  - Palmitate induces transcriptional regulation of BACE1 and presenilin by STAT3 in
      neurons mediated by astrocytes.
AB  - Deregulation of calcium has been implicated in neurodegenerative diseases,
      including Alzheimer's disease (AD). Previously, we showed that saturated free
      fatty acid, palmitate, causes AD-like changes in primary cortical neurons
      mediated by astrocytes. However, the molecular mechanisms by which conditioned
      medium from astrocytes cultured in palmitate induce AD-like changes in neurons
      are unknown. This study demonstrates that this condition medium from astrocytes
      elevates calcium level in the neurons, which subsequently increases calpain
      activity, a calcium-dependent protease, leading to enhance p25/Cdk5 activity and
      phosphorylation and activation of the STAT3 (signal transducer and activator of
      transcription) transcription factor. Inhibiting calpain or Cdk5 significantly
      reduces the upregulation in nuclear level of pSTAT3, which we found to
      transcriptionally regulate both BACE1 and presenilin-1, the latter is a catalytic
      subunit of gamma-secretase. Decreasing pSTAT3 levels reduced the mRNA levels of
      both BACE1 and presenilin-1 to near control levels. These data demonstrate a
      signal pathway leading to the activation of STAT3, and the generation of the
      amyloid peptide. Thus, our results suggest that STAT3 is an important potential
      therapeutic target of AD pathogenesis. 

PMID- 23968648
TI  - Dural ectasia in Marfan's syndrome: magnetic resonance imaging appearances and
      anaesthetic experience of three deliveries.
AB  - Neuraxial anaesthetic techniques are considered useful to minimise haemodynamic
      stress during labour. In Marfan's syndrome, connective tissue abnormalities not
      only affect the thoracic aorta but also predispose to dural ectasia. A dural
      ectatic sac may cause difficulties with neuraxial analgesia and anaesthesia. We
      discuss magnetic resonance imaging appearances and anaesthetic experience of
      three deliveries in a parturient with stable echocardiographic findings. We
      consider that epidural analgesia and anaesthesia are a safe and pragmatic
      solution for labour and delivery. Lumbo-sacral magnetic resonance imaging at
      presentation will define dural ectasia and assist in management. 

PMID- 23968649
TI  - Nintendo Wii rehabilitation ("Wii-hab") provides benefits in Parkinson's disease.
AB  - Parkinson's disease (PD) impairs both activities of daily living (ADLs) and motor
      function and has adverse effects on mood in many patients. While dopaminergic
      medications are quite helpful for motor and ADLs impairments in PD, complementary
      therapies are also important in helping patients achieve maximum benefits and
      quality of life. We hypothesized that the Nintendo Wii (Wii) is a useful tool in
      improving motor and non-motor aspects in patients with PD, given its ability to
      drive functional movements and interactive nature. We enrolled twenty subjects
      with early to mid-stage PD in an open-label within-subjects study design where
      each subject was evaluated at baseline and then re-evaluated after playing the
      Wii three times per week for four weeks. Subjects were then re-evaluated one
      month later after not playing the Wii for a month to see if effects carried over.
      Subjects demonstrated significant improvements in the primary outcome measure
      (Nottingham Extended Activities of Daily Living Test (NEADL)), quality of life
      (PDQ-39) and motor function (UPDRS), and a trend toward improved mood (HAM-D)
      after four weeks of Wii therapy. Follow-up assessments one month later showed
      continued improvement for quality of life and UPDRS scores. The results
      demonstrate that Wii therapy provides short-term motor, non-motor, and quality of
      life benefits in PD. Further studies are needed to determine if there are long
      term benefits of Wii therapy in PD. 

PMID- 23968650
TI  - Morphea and Parry-Romberg syndrome associated with a mixed movement disorder.

PMID- 23968651
TI  - Predictors of survival in a series of clinically diagnosed progressive
      supranuclear palsy patients.
AB  - BACKGROUND: Investigations into prognostic factors in progressive supranuclear
      palsy have shown conflicting results. We performed a retrospective study in order
      to identify clinical predictors of survival in clinically diagnosed progressive
      supranuclear palsy patients referred to our centre. METHODS: Data on medical
      history, survival and five clinical disability milestones (inability to walk
      unassisted, unintelligible speech, severe dysphagia, dementia and
      institutionalization) were collected from outpatients' medical records and by a
      telephone interview to caregivers. Patients were subdivided into Richardson's
      syndrome and PSP-Parkinsonism according to symptoms during the first 2 years of
      disease. Survival was analyzed by the Kaplan-Meier method and Cox regression
      analysis. RESULTS: Forty-three consecutive patients were enrolled (86%
      Richardson's syndrome). Motor disturbances were the most frequent symptoms of
      onset. During the follow-up, 60.5% of patients died after a median survival of
      7.1 years (2.2-18). Older age at onset (>63) (HR 2.8; 95% CI: 1.3-5.7; p =
      0.007), early dysphagia (HR 2.3; 95% CI: 1-5.3; p = 0.05) and early cognitive
      deficits (HR 3.6; 95% CI: 1.6-8.2; p = 0.002) were predictors of shorter
      survival. Compared to PSP-Parkinsonism patients, Richardson's syndrome patients
      had shorter survival and higher mortality risk although not statistically
      significant (HR 3 95% CI: 0.9-9.9; p = 0.07). Seventy-seven percent of patients
      developed severe disability during follow-up: shorter time to the first clinical
      disability milestone predicted shorter survival (HR 7.8; 95% CI: 2.3-26; p =
      0.0008). CONCLUSIONS: early dysphagia, cognitive impairment, older age at onset,
      and time to disability were predictors of shorter survival; Richardson's syndrome
      had a less favorable course than PSP-Parkinsonism. Clinical milestones should be
      considered as possible endpoints in future clinical trials.

PMID- 23968653
TI  - Repetitive transcranial magnetic stimulation--an alternative treatment for
      chronic refractory pain.

PMID- 23968652
TI  - Influence of electron dose rate on electron counting images recorded with the K2
      camera.
AB  - A recent technological breakthrough in electron cryomicroscopy (cryoEM) is the
      development of direct electron detection cameras for data acquisition. By
      bypassing the traditional phosphor scintillator and fiber optic coupling, these
      cameras have greatly enhanced sensitivity and detective quantum efficiency (DQE).
      Of the three currently available commercial cameras, the Gatan K2 Summit was
      designed specifically for counting individual electron events. Counting further
      enhances the DQE, allows for practical doubling of detector resolution and
      eliminates noise arising from the variable deposition of energy by each primary
      electron. While counting has many advantages, undercounting of electrons happens
      when more than one electron strikes the same area of the detector within the
      analog readout period (coincidence loss), which influences image quality. In this
      work, we characterized the K2 Summit in electron counting mode, and studied the
      relationship of dose rate and coincidence loss and its influence on the quality
      of counted images. We found that coincidence loss reduces low frequency
      amplitudes but has no significant influence on the signal-to-noise ratio of the
      recorded image. It also has little influence on high frequency signals. Images of
      frozen hydrated archaeal 20S proteasome (~700 kDa, D7 symmetry) recorded at the
      optimal dose rate retained both high-resolution signal and low-resolution
      contrast and enabled calculating a 3.6 A three-dimensional reconstruction from
      only 10,000 particles.

PMID- 23968654
TI  - Different dosing regimens for propofol induction in obese patients.
AB  - OBJECTIVES: The aim of the study is to investigate the efficacy of different
      dosages of single bolus propofol administered on the basis of total body weight
      or corrected body weight for the intravenous induction of anesthesia in obese
      patients undergoing bariatric surgery. MATERIALS AND METHODS: Thirty-eight obese
      patients with a body mass index (BMI) of 30 kg/m(2) or greater were randomly
      divided into two groups. They received single-bolus propofol (2 mg/kg) for
      intravenous induction of anesthesia based on either total body weight (TBW; 20
      patients) or corrected body weight 60% (CBW60; 18 patients). Patients'
      characteristics, biochemical data, monitored bispectral index (BIS) values, and
      hemodynamic parameters were compared between the two groups. RESULTS: The
      propofol dose was significantly lower in the CBW60 group than in the TBW group
      (189.5 +/- 36.3 mg vs. 217.3 +/- 39.1 mg, respectively; p = 0.03). The highest
      BIS value, representing potential awareness after intubation, was relatively
      higher in the CBW60 group, but this difference was not statistically significant
      (CBW60 group, 53.6 +/- 11.1; TBW group, 48.6 +/- 8.1; p = 0.22). Eighty-three
      percent of patients experienced hypotension during induction and at least 44%
      patients showed marked hypotension. There was no significant difference between
      the TBW and CBW60 groups in blood pressure after intubation. CONCLUSION: When
      using single bolus propofol, the CBW60 group showed similar BIS values and
      hemodynamic effects as the TBW group during the intravenous induction of general
      anesthesia for obese patients.

PMID- 23968655
TI  - A combination of the modified Mallampati score, thyromental distance, anatomical
      abnormality, and cervical mobility (M-TAC) predicts difficult laryngoscopy better
      than Mallampati classification.
AB  - OBJECTIVE: Unanticipated difficult tracheal intubation is a significant source of
      morbidity and mortality in anesthetized patients. A number of modules have been
      developed to predict difficult airways, but they are often complex in nature. We
      combined the modified Mallampati score (M), thyromental distance (T), anatomical
      abnormality (A), and cervical mobility (C) into a single scoring system with the
      acronym M-TAC, and evaluated it against Mallampati scoring. METHODS: We
      prospectively analyzed 500 adult patients of the American Society of
      Anesthesiologists (ASA) class I or II, scheduled for elective surgery under
      general anesthesia. Preoperative airway assessments using M-TAC were performed,
      all of which were given a score. Anesthesiologists, blinded to the pre-anesthetic
      airway assessment, performed laryngoscopy and graded the laryngoscopic view as
      per Cormack and Lehane's classification. For the study purpose, difficult
      laryngoscopy was defined as Cormack and Lehane Grade 3 or 4 of laryngoscopic
      view. RESULTS: An M-TAC score >= 4 had a significantly higher sensitivity (96%
      vs. 72%) and specificity (86% vs. 78%) with a high positive predictive value (44%
      vs. 28%) and a very low false negative value (2% vs. 15%) in comparison with
      Mallampati scoring (p < 0.05). Analysis of the receiver operating characteristic
      (ROC) curve for predicting difficult laryngoscopy revealed an area under the
      curve of 0.83 (95% CI = 0.78-0.88) for Mallampati scoring and 0.94 (95% CI = 0.92
      0.96) for M-TAC scoring system. CONCLUSION: The M-TAC scoring system has provided
      a higher sensitivity and specificity in predicting difficult laryngoscopy in
      comparison with Mallampati classification.

PMID- 23968656
TI  - Addition of dexmedetomidine to ropivacaine improves cervical plexus block.
AB  - OBJECTIVE: To investigate the sensory block onset time, duration time, and side
      effects of adding dexmedetomidine to ropivacaine for cervical plexus block.
      METHODS: Forty American Society of Anesthesiologists (ASA) Class I or II adult
      patients who were scheduled to undergo thyroid surgery were randomly allocated to
      the following groups to receive cervical plexus block: 30 mL of 0.375%
      ropivacaine combined with 1 MUg kg(-1) of dexmedetomidine; 30 mL of 0.375%
      ropivacaine combined with saline (control). The sensory block onset time,
      duration of analgesia, mean arterial pressure (MAP), heart rate (HR), and the
      incidences of side effects, such as hypotension, bradycardia, and hypoxemia were
      recorded. RESULTS: The addition of dexmedetomidine to ropivacaine (Group D)
      shortened the sensory block onset time compared with the ropivacaine group (Group
      C) (95% confidence interval [CI] 4.18-5.26; p < 0.05). The duration of analgesia
      of cervical plexus block in Group D was significantly longer than that in Group C
      (95% CI 295.96-311.12; p < 0.05). The Ramsay sedation score at 5, 10, 20, 40, 60,
      90, and 120 minutes after local anesthetic administration in Group D was
      significantly higher than that in Group C (p < 0.05). MAP level and HR level in
      Group D were significantly lower than that in Group C (p < 0.05). CONCLUSION: The
      addition of 1 MUg kg(-1) dexmedetomidine to ropivacaine for cervical plexus block
      could shorten the sensory block onset time and extend the duration of analgesia,
      and increased the quality of analgesia, with the patients being sedated and
      arousable.

PMID- 23968657
TI  - Hyperglycemia is associated with poor outcomes in surgical critically ill
      patients receiving parenteral nutrition.
AB  - BACKGROUND AND AIMS: Hyperglycemia, a major side effect of patients receiving
      total parenteral nutrition (PN), is associated with higher mortality in
      critically ill patients. The aim of this study was to determine whether elevated
      blood glucose levels would be associated with worse outcomes in patients
      receiving PN. METHODS: This retrospective study included postoperative patients
      admitted to our surgical intensive care unit (SICU) from July 2008 to June 2009.
      Data collected included blood glucose levels, length of stay, and outcome
      measures. Correlations among daily average, maximum, and minimum blood glucose
      levels and outcome measures were calculated. RESULTS: Sixty-nine patients were
      enrolled and divided into PN (n = 40) and non-PN (n = 29) groups. The initial
      mean blood glucose levels were 138.4 +/- 63.1 mg/dL and 123.2 +/- 41.8 mg/dL for
      the PN and non-PN groups, respectively. The mean blood glucose concentration was
      significantly increased (DeltaBS = 44.8 +/- 57.3 mg/dL; p < 0.001) in the PN
      group compared with the non-PN group (DeltaBS = 39.4 +/- 67.0 mg/dL; p = 0.004).
      The blood glucose concentration was significantly increased and consequently,
      consumption of insulin was increased on the 2(nd) day of ICU admission. The risk
      of mortality increased by a factor of 1.3 (OR = 1.30, 95% CI = 1.07-1.59, p =
      0.010) for each 10 mg/dL increase in blood glucose level, when the daily maximum
      blood glucose level was >250 mg/dL. There were no cases of mortality in the
      current study when the blood glucose levels were controlled below 180 mg/dL. The
      mean blood glucose level in patients receiving PN was higher in those with
      diabetes than in those without diabetes (215.5 +/- 42.8 vs. 165.8 +/- 42.0 mg/dL,
      respectively, p = 0.001). CONCLUSION: The blood glucose level was associated with
      patient outcome and should be intensively monitored in critically ill surgical
      patients. We suggest that blood glucose levels should be controlled below 180
      mg/dL in postoperative critically ill patients.

PMID- 23968658
TI  - Thalamus and pain.
AB  - The thalamus is a key relay station for the transmission of nociceptive
      information to the cerebral cortex. We review the input-output connection,
      functional imaging, direct neuronal recording, stimulation, and lesioning studies
      on the involvement of thalamus in acute and chronic pain functions. Based on its
      specific reciprocal connection with the cerebral cortex, strong nociceptive
      responsiveness, and the severe chronic pain when it is damaged, the thalamus may
      hold the key to pain consciousness and the key to understanding spontaneous and
      evoked pain in chronic pain conditions. A work plan is proposed for future study.

PMID- 23968659
TI  - Efficacy and practical issues of repetitive transcranial magnetic stimulation on
      chronic medically unexplained symptoms of pain.
AB  - Chronic pain is a common issue worldwide and remains a big challenge to
      physicians, particularly when the underlying causes do not meet any specific
      disease for settlement. Such medically unexplained somatic symptoms of pain that
      lack an integrated diagnosis in medicine have a high psychiatric comorbidity such
      as depression, and will require a multidisciplinary treatment strategy for a
      better outcome. Thus, most patients deserted management in spite of being
      inadequately treated and even presented with high resistance to analgesic drugs.
      Noninvasive brain stimulation, including repetitive transcranial magnetic
      stimulation (rTMS), has been used to treat refractory neuropathic pain and the
      analgesic efficacy is promising. So far, some case series and randomized rTMS
      studies have reported on patients with certain medically unexplained symptoms
      (MUSs) of pain (e.g., psychogenic pain or somatic symptoms in major depression
      and fibromyalgia). However, there is still no review article that is specific to
      the efficacy of rTMS on chronic unexplained symptoms of pain. Therefore, in the
      present review, we ventured to clarify the terminology and summarized the
      analgesic effects of rTMS on chronic MUSs of pain. 

PMID- 23968660
TI  - Homemade rubber spacer for endotracheal tube holder.

PMID- 23968661
TI  - A novel modified method of using Trachway intubating stylet for awake tracheal
      intubation in patients with anticipated difficult airway.
AB  - The Trachway intubating stylet is designed to facilitate tracheal intubation in
      anesthetized patients with a normal or difficult airway anatomy. The shortcoming
      of this device is the lack of a working channel to provide topicalization of the
      airway. We describe a novel modified method of using Trachway intubating stylet
      to provide airway topicalization and perform awake orotracheal intubation in two
      cases with an anticipated difficult airway. The first case was a superobese
      patient with a cervical spine disorder, whereas the second case was a patient
      with an enlarged thyroid gland. Transtracheal lidocaine injection was technically
      difficult in these patients because of neck obesity and thyroid enlargement,
      respectively. We believe that this modified method can be used to provide
      effective airway topicalization when Trachway intubating stylet is used for awake
      orotracheal intubation. 

PMID- 23968662
TI  - Diagnostic dilemma: rare case of recurrent d-lactic acidosis leading to recurrent
      acute cardiac failure.
AB  - d-Lactic acidosis is a rare form of anion gap acidosis and requires a high index
      of suspicion for appropriate diagnosis and treatment. We report a rare case of
      short bowel syndrome with recurrent episodes of antibiotic-induced d-lactic
      acidosis with the presentation of transient severe left ventricular failure. The
      patient's cardiac function returned to normal with the resolution of acidosis
      under conservative management and a low carbohydrate diet. d-Lactic acidosis has
      been known to be associated with only neurological symptoms, and cardiac failure
      has not been previously reported. 

PMID- 23968663
TI  - Two-person technique for fiberscope-aided nasotracheal intubation in anesthetized
      patients.

PMID- 23968664
TI  - CobraPLA-guided tracheal intubation for airway rescue in a child with large
      orofacial arteriovenous malformation.

PMID- 23968666
TI  - Associations of sire estimated breeding values and objective meat quality
      measurements with sensory scores in Australian lamb.
AB  - The impact of selecting for lean meat yield using breeding values for increased
      eye muscle depth (PEMD) and decreased fat depth (PFAT) on the consumer acceptance
      of lamb meat was evaluated. Consumer sensory scores (tenderness, juiciness,
      flavour, odour, overall liking) were obtained for the longissimus lumborum (loin)
      and semimembranosus (topside) muscles of 1471 lambs. On average loin samples were
      more acceptable for consumers. Sensory scores increased with higher IMF levels,
      with lower shear force levels, and when animals were younger and less muscular.
      Increasing PEMD decreased tenderness, overall liking and flavour scores in both
      muscles, and decreasing PFAT reduced tenderness within the loin samples only.
      This negative impact of PEMD and PFAT is not solely driven through the phenotypic
      impact of IMF and shear force on sensory scores. Our results confirm the growing
      concerns that selecting for lean meat yield would reduce consumer eating quality,
      and highlight that careful monitoring of selection programmes is needed to
      maintain lamb eating quality. 

PMID- 23968665
TI  - Lipidated steroid saponins from Dioscorea villosa (wild yam).
AB  - Two groups of lipidated steroid saponins including seven new compounds (2, 3, 5,
      and 7-10) were isolated from the widely used botanical, wild yam (Dioscorea
      villosa), employing a fractionation protocol of metabolomic mining. This
      methodology recently led to the isolation of 14 diarylheptanoids from the same
      plant. Together with these lipidated steroid saponins, they establish additional
      new markers for D. villosa. The lipidation of steroids with analog long-chain
      fatty acids containing different degrees of unsaturation generates an entire
      series of compounds which are difficult to purify and analyze. The structures of
      the two series of lipidated steroid saponins (series A and B) were established by
      a combination of 1D and 2D NMR as well as GC-MS after chemical modification.
      Series A was determined to be a mixture of lipidated spirostanol glycosides (1
      5), while series B (6-10) was proved to be a mixture of five lipidated
      clionasterol glucosides. The latter group represents the first derivatives of
      clionasterol to be found in D. villosa. The discovery of this specific structural
      type of aliphatic esters of steroid saponins expands the characterization of the
      secondary metabolome of D. villosa. It may also inspire biological studies which
      take into account the lipophilic character and significantly altered
      physiochemical characteristics of these otherwise relatively polar
      phytoconstituents. 

PMID- 23968667
TI  - Risk factors for squamous cell carcinoma, a study by the National Dermatology
      Centre of Colombia.
AB  - INTRODUCTION: Nonmelanoma skin cancer is the most common malignancy in white
      individuals. The risk factors for squamous cell carcinoma, which belongs to the
      family of nonmelanoma skin cancers, have not been studied in Colombia. OBJECTIVE:
      To determine the risk factors for squamous cell carcinoma in patients at a
      national referral center for skin diseases in Colombia. MATERIAL AND METHODS: We
      conducted a case-control study that evaluated sociodemographic, epidemiological,
      and clinical factors among 332 individuals. Risk was calculated as odds ratio
      (ORs) using the multivariate conditional logistic regression analysis method.
      RESULTS: The following risk factors were identified: family history of skin
      cancer (OR, 6.55; 95% CI, 1.4-28.9), living in a rural area after the age of 30
      years (OR, 3.13; 95% CI, 1.3-7.2), a lifetime working outdoors (OR, 2.98; 95% CI,
      1.5-5.7), smoking more than 10 cigarettes a day (OR, 2.96; 95% CI, 1.3-6.5),
      actinic conjunctivitis (OR, 2.68; 95% CI, 1.2-5.9), poikiloderma of Civatte (OR,
      3.29; 95% CI, 1.7-6.1), numerous facial actinic keratoses (OR, 9.23; 95% CI, 4.9
      17.1), and numerous freckles (OR, 3.68; 95% CI, 1.3-10.1). CONCLUSIONS: We have
      documented clinical characteristics and personal history factors that should
      guide the physician in making decisions on the preventive and follow-up measures
      to be adopted for individuals at risk of squamous cell carcinoma. These findings
      may help guide policy for controlling the disease using local information.

PMID- 23968668
TI  - Development of critical attitude in fundamentals of professional care discipline:
      a case study.
AB  - This is a qualitative case study to identify the contributions of a critical
      pedagogical technique in developing critical attitudes of graduating nursing
      students in Brazil. Fourteen students participated in this study. Data were
      collected from March to August 2010 using triangulation of non-participant
      observation, interview and document analysis. The collected data were transcribed
      to Word documents, which were subsequently imported into ATLAS.ti, version 6.2,
      for organisation and qualitative data analysis. The analysis was based on the
      work of Minayo (2010). The following three thematic analysis units were
      constructed: feeling free - seeking the liberty to learn to admire, admiring by
      curiosity and reflecting about the admired object. The results of the thematic
      categories reveal that the students understand that they are free to have an
      active role in their education, and the teacher facilitates this process; thus,
      the students have a raison d'etre, or reason for being, free. Feeling free, the
      student can exercise their curiosity when facing the given situations and topics,
      which challenges them to make decisions based on their awareness of the world. 

PMID- 23968669
TI  - Path dependence and health policy: intersections between the past and the future.

PMID- 23968670
TI  - Reforming Canadian primary care - don't stop half-way.
AB  - Strong primary care is a fundamental underpinning of high-performing health
      systems. Sadly, primary care infrastructure and performance in canada lag behind
      many of our international peers. Although substantial reforms have been
      implemented over the past decade, progress has been uneven, and no province has
      all the essential system elements in place. Continued investment is both needed
      and affordable. However, whether those investments - and others necessary to
      strengthen medicare - are made will be determined largely by the ongoing clash
      between communitarian and libertarian values. 

PMID- 23968671
TI  - Alternative level of care: Canada's hospital beds, the evidence and options.
AB  - Patients designated as alternative level of care (ALC) are an ongoing concern for
      healthcare policy makers across Canada. These patients occupy valuable hospital
      beds and limit access to acute care services. The objective of this paper is to
      present policy alternatives to address underlying factors associated with ALC bed
      use. Three alternatives, and their respective limitations and structural
      challenges, are discussed. Potential solutions may require a mix of policy
      options proposed here. Inadequate policy jeopardizes new acute care activity
      based funding schemes in British Columbia and Ontario. Failure to address this
      issue could exacerbate pressures on the existing bottlenecks in the community
      care system in these and other provinces. 

PMID- 23968672
TI  - Cost-control mechanisms in Canadian private drug plans.
AB  - Approximately 68% of Canadians receive prescription drug coverage through an
      employer-sponsored private plan. However, we have very limited data on the
      structure of these plans. This study aims to identify and describe the use of
      cost-control mechanisms in private drug plans in Canada and describe what private
      coverage looks like for the average Canadian. Using 2010 data from over 113,000
      different private drug plans, provided by Applied Management Consultants, we
      determined the overall use of key cost-control measures, and the cost-control
      tools that appear to be gaining currency compared to a report on benefits
      coverage in 1998. We found that the use of common cost-control measures is
      relatively low among Canadian private benefits programs. Co-insurance is much
      more common in private coverage plans than co-payments. Deductibles are uncommon
      in Canada and, when in place, are very small. The use of annual and lifetime
      maximums is increasing. Canadian private benefits programs use few cost-control
      measures to respond to increasing costs, particularly in comparison to their
      public counterparts. These results suggest there are ample opportunities for
      greater efficiency in private sector drug coverage plans. 

PMID- 23968673
TI  - High-cost users of Ontario's healthcare services.
AB  - Approximately 1.5% of ontario's population, represented by the top 5% highest
      cost-incurring users of ontario's hospital and home care services, account for
      61% of hospital and home care costs. Similar studies from other jurisdictions
      also show that a relatively small number of people use a high proportion of
      health system resources. Understanding these high-cost users (hcus) can inform
      local healthcare planners in their efforts to improve the quality of care and
      reduce burden on patients and the healthcare system. To facilitate this
      understanding, we created a profile of hcus using demographic and clinical
      characteristics. The profile provides detailed information on hcus by care type,
      geography, age, sex and top clinical conditions. 

PMID- 23968674
TI  - Coalition Priorite Cancer and the pharmaceutical industry in Quebec: conflicts of
      interest in the reimbursement of expensive cancer drugs?
AB  - In the context of scarce public resources, patient interest groups have
      increasingly turned to private organizations for financing, including the
      pharmaceutical industry. This practice puts advocacy groups in a situation of
      potential conflicts between the interests of patients and those of the drug
      companies. The interests of patients and industry can converge on issues related
      to the approval and reimbursement of medications. But even on this issue,
      interests do not always align perfectly. Using the Quebec example of Coalition
      Priorite Cancer (CPC) as a case study, we examine the ethical issues raised by
      such financial relationships in the context of drug reimbursement decision
      making. We collected, compiled and analyzed publicly available information on the
      CPC's organization and activities; this approach allowed us to raise and discuss
      important questions regarding the possible influence exerted on patient groups by
      donors. We conclude with some recommendations. 

PMID- 23968675
TI  - Product listing agreements (PLAs): a new tool for reaching Quebec's
      pharmaceutical policy objectives?
AB  - Product listing agreements (PLAs) with pharmaceutical manufacturers are
      increasingly viewed as an innovative and useful tool in the effort to control
      drug expenditures. To date, Quebec is the only province that has been reluctant
      to enter into such agreements, arguing that their confidential nature may lead to
      a disparity in coverage between individuals covered by the public plan and those
      covered by private insurance. While PLAs may, in fact, present such a risk, in
      this paper we will argue that when used correctly, these agreements are actually
      tools that could help attain all four of the objectives set out in Quebec's
      policy on medications, namely: (a) improved access to drugs, (b) fair and
      reasonable drug pricing, (c) optimal drug use and (d) maintaining a dynamic
      biopharmaceutical industry in Quebec. 

PMID- 23968676
TI  - Adverse events associated with hospitalization or detected through the RAI-HC
      assessment among Canadian home care clients.
AB  - BACKGROUND: The occurrence of adverse events (AEs) in care settings is a patient
      safety concern that has significant consequences across healthcare systems.
      Patient safety problems have been well documented in acute care settings;
      however, similar data for clients in home care (HC) settings in Canada are
      limited. The purpose of this Canadian study was to investigate AEs in HC,
      specifically those associated with hospitalization or detected through the
      Resident Assessment Instrument for Home Care (RAI-HC). METHOD: A retrospective
      cohort design was used. The cohort consisted of HC clients from the provinces of
      Nova Scotia, Ontario, British Columbia and the Winnipeg Regional Health
      Authority. RESULTS: The overall incidence rate of AEs associated with
      hospitalization ranged from 6% to 9%. The incidence rate of AEs determined from
      the RAI-HC was 4%. Injurious falls, injuries from other than fall and medication
      related events were the most frequent AEs associated with hospitalization,
      whereas new caregiver distress was the most frequent AE identified through the
      RAI-HC. CONCLUSION: The incidence of AEs from all sources of data ranged from 4%
      to 9%. More resources are needed to target strategies for addressing safety risks
      in HC in a broader context. Tools such as the RAI-HC and its Clinical Assessment
      Protocols, already available in Canada, could be very useful in the assessment
      and management of HC clients who are at safety risk.

PMID- 23968677
TI  - The association between health information technology adoption and family
      physicians' practice patterns in Canada: evidence from 2007 and 2010 National
      Physician Surveys.
AB  - OBJECTIVE: To describe the association between health information technology
      (HIT) adoption and family physicians' patient visit length in Canada after
      controlling for physician and practice characteristics. METHOD: HIT adoption is
      defined in terms of four types of HIT usage: no HIT use (NO), basic HIT use
      without electronic medical record system (HIT), basic HIT use with electronic
      medical record (EMR) and advanced HIT use (EMR + HIT). The outcome variable is
      the average time spent on a patient visit (visit length). The data for this study
      came from the 2007 and 2010 National Physician Surveys. A log-linear model was
      used to analyze our visit length outcome. RESULTS: The average time worked per
      week was found to be in the neighbourhood of 36 hours in both 2007 and 2010, but
      users of EMR and EMR + HIT were undertaking fewer patient visits per week
      relative to NO users. Multivariable analysis showed that EMR and EMR + HIT were
      associated with longer average time spent per patient visit by about 7.7%
      (p<0.05) and 6.7% (p<0.01), respectively, compared to NO users in 2007. In 2010,
      EMR was not statistically significant and EMR + HIT was associated with a 4%
      (p<0.1) increased visit length. A variety of practice-related variables such as
      the mode of remuneration, work setting and interprofessional practice influenced
      visit length in the expected direction. CONCLUSION: Use of HIT is found to be
      associated with fewer patient visits and longer visit length among family
      physicians in Canada relative to NO users, but this association weakened in the
      multivariable analysis of 2010.

PMID- 23968678
TI  - Livestock density as risk factor for livestock-associated methicillin-resistant
      Staphylococcus aureus, The Netherlands.

PMID- 23968679
TI  - How do we integrate man with machine in our resuscitation efforts?

PMID- 23968680
TI  - Which airway for cardiac arrest? Do supraglottic airways devices have a role?

PMID- 23968681
TI  - Effects of limiting anterior displacement of the center of foot pressure on
      anticipatory postural control during bilateral shoulder flexion.
AB  - In bilateral shoulder flexion with the arms moving from the sides of the body to
      the horizontal level while standing, no preceding activation of the triceps surae
      (TS) with respect to focal muscles has been found. Considering that preceding
      activation would offer a useful indicator of anticipatory postural control, it
      was attempted to induce preceding activation by limiting the anterior
      displacement range of the center of foot pressure in the anteroposterior
      direction (CoPap). Subjects were 13 healthy young adults. The 50% anterior range
      of CoPap displacement caused by shoulder flexion was calculated, and the floor
      inclined by the subject's weight when CoPap extended beyond that range. Subjects
      were instructed not to incline the floor during shoulder flexion. Under the
      limitation condition, the ankle and knee joints plantarflexed and extended at 1.1
      degrees , respectively, with no hip movement; that is, the whole body inclined
      backward by pivoting at the ankle. This limitation resulted in preceding muscle
      activation of TS as well as erector spinae and biceps femoris, and no significant
      differences in onset time were seen between these muscles. These results
      demonstrated that by limiting CoPap anterior displacement, preceding activation
      of TS could be induced with backward inclination of the whole body. 

PMID- 23968682
TI  - Rotator cuff muscle function and its relation to scapular morphology in apes.
AB  - It is widely held that many differences among primate species in scapular
      morphology can be functionally related to differing demands on the shoulder
      associated with particular locomotor habits. This perspective is largely based on
      broad scale studies, while more narrow comparisons of scapular form often fail to
      follow predictions based on inferred differences in shoulder function. For
      example, the ratio of supraspinous fossa/infraspinous fossa size in apes is
      commonly viewed as an indicator of the importance of overhead use of the
      forelimb, yet paradoxically, the African apes, the most terrestrial of the great
      apes, have higher scapular fossa ratios than the more suspensory orangutan. The
      recent discovery of several nearly complete early hominin scapular specimens, and
      their apparent morphological affinities to scapulae of orangutans and gorillas
      rather than chimpanzees, has led to renewed interest in the comparative analysis
      of human and extant ape scapular form. To facilitate the functional
      interpretation of differences in ape scapulae, particularly in regard to relative
      scapular fossa size, we used electromyography (EMG) to document the activity
      patterns in all four rotator cuff muscles in orangutans and gibbons, comparing
      the results with previously published data for chimpanzees. The EMG results
      indicate that the distinctive contributions of each cuff muscle to locomotion are
      the same in the three ape species, failing to support inferences of differences
      in rotator cuff function based on relative scapular fossa size comparisons. It is
      also shown that relative scapular fossa size is not in fact a good predictor of
      either the relative masses or cross-sectional areas of the rotator cuff muscles
      in apes, and relative fossa size gives a false impression of the importance of
      individual cuff muscles to locomotor differences among apes. A possible
      explanation for the disparity between fossa and muscle size relates to the
      underappreciated role of the scapular spine in structural reinforcement of the
      blade. 

PMID- 23968683
TI  - Provenancing silcrete in the Cape coastal zone: implications for Middle Stone Age
      research in South Africa.

PMID- 23968684
TI  - Transcription factor-induced enhancer modulations during cell fate conversions.
AB  - The activity of transcription factors (TFs) has empowered the reprogramming of
      differentiated cells into induced pluripotent stem cells (iPSCs) and alternative
      lineages. Elucidation of the molecular mechanisms underpinning these processes
      has expanded our understanding of how novel gene expression programs become
      activated while old ones are silenced. How TFs modify chromatin and activate
      requisite enzymes during these processes has recently been discussed in several
      excellent reviews. Here we discuss the questions of how ectopically expressed TFs
      access chromatin to modulate enhancers and establish a novel transcriptome during
      cell reprogramming, lineage conversions and differentiation.

PMID- 23968685
TI  - Secondary cell reprogramming systems: as years go by.
AB  - The groundbreaking discovery of the induced pluripotent stem cells in 2006
      brought a major paradigm shift in our understanding of the plasticity of
      differentiated cells. An unprecedented effort has been invested to elucidate the
      underpinning molecular mechanisms of the dramatic changes in cell properties,
      using the powerful secondary reprogramming systems (2 degrees RS). This review
      outlines the key components of the 2 degrees RS, its recent development and
      applications that have led to a deeper understanding of the 'magic' of induced
      cell fate changes.

PMID- 23968686
TI  - Molecular characterization and antigenic properties of a novel Babesia gibsoni
      glutamic acid-rich protein (BgGARP).
AB  - Identification and molecular characterization of Babesia gibsoni proteins with
      potential antigenic properties are crucial for the development and validation of
      the serodiagnostic method. In this study, we isolated a cDNA clone encoding a
      novel B. gibsoni 76-kDa protein by immunoscreening of the parasite cDNA library.
      Computer analysis revealed that the protein presents a glutamic acid-rich region
      in the C-terminal. Therefore, the protein was designated as B. gibsoni glutamic
      acid-rich protein (BgGARP). A BLASTp analysis of a translated BgGARP polypeptide
      demonstrated that the peptide shared a significant homology with a 200-kDa
      protein of Babesia bigemina and Babesia bovis. A truncated BgGARP cDNA (BgGARPt)
      encoding a predicted 13-kDa peptide was expressed in Escherichia coli (E. coli),
      and mouse antisera against the recombinant protein were used to characterize a
      corresponding native protein. The antiserum against recombinant BgGARPt
      (rBgGARPt) recognized a 140-kDa protein in the lysate of infected erythrocytes,
      which was detectable in the cytoplasm of the parasites by confocal microscopic
      observation. In addition, the specificity and sensitivity of enzyme-linked
      immunosorbent assay (ELISA) with rBgGARPt were evaluated using B. gibsoni
      infected dog sera and specific pathogen-free (SPF) dog sera. Moreover, 107 serum
      samples from dogs clinically diagnosed with babesiosis were examined using ELISA
      with rBgGARPt. The results showed that 86 (80.4%) samples were positive by
      rBgGARPt-ELISA, which was comparable to IFAT and PCR as reference test. Taken
      together, these results demonstrate that BgGARP is a suitable serodiagnostic
      antigen for detecting antibodies against B. gibsoni in dogs. 

PMID- 23968687
TI  - Miltefosine resistance in Leishmania donovani involves suppression of oxidative
      stress-induced programmed cell death.
AB  - Miltefosine (MIL), an alkylphospholipid, is the first orally administrable anti
      leishmanial drug. But due to its long half-life, miltefosine is highly vulnerable
      for resistance. Hence it is important to understand the mechanism of resistance
      and to elucidate its action on Leishmania. Here we investigate the miltefosine
      induced process of programmed cell death in wild type (miltefosine sensitive) and
      in laboratory generated resistant strains of Leishmania donovani. Results
      indicate that miltefosine induced apoptosis like death in a time and dose
      dependent manner in wild-type cells, but not in MIL-resistant cell line. The
      miltefosine resistant cells remained protected against miltefosine-induced loss
      of mitochondrial membrane potential, gradual ATP loss and cytochrome C release
      from mitochondria into the cytosol. Comparative transcriptomic study showed
      significantly increased expression of FeSODA and SIR2 genes, putatively involved
      in oxidative stress associated apoptotic cell death. We hypothesize that
      oxidative stress mediated apoptosis as an alternative mechanism of miltefosine
      resistance. 

PMID- 23968688
TI  - Heligmosomoides polygyrus infection reduces severity of type 1 diabetes induced
      by multiple low-dose streptozotocin in mice via STAT6- and IL-10-independent
      mechanisms.
AB  - Some parasitic helminths are known to protect their hosts from allergic and
      autoimmune disorders. Here, we tested the effects of a gastrointestinal nematode,
      Heligmosomoides polygyrus (Hp), on streptozotocin (STZ)-induced type 1 diabetes
      (T1D) in mice. Hp infection significantly suppressed hyperglycemia induced by
      multiple low-dose administration of STZ, but did not affect hyperglycemia induced
      by single high-dose administration of STZ. In the multiple low dose model, Hp
      infection prevented a decrease in pancreatic islet size. The augmentation of TNF
      alpha and IL-1beta expression in the pancreas was abrogated by Hp infection. The
      genetic absence of IL-10 or STAT6 did not abrogate the anti-hyperglycemic effect
      of Hp. Hp has a suppressive effect on immune mechanism-mediated experimental T1D
      via Th2 polarization-independent mechanisms. 

PMID- 23968689
TI  - Skin color has no impact on motor resonance: evidence from mu rhythm suppression
      and imitation.
AB  - It has been suggested that physical similarity with an observed model facilitates
      action-perception and understanding. Indeed, a number of studies have shown that
      observing actors of one's own race facilitate motor, sensory and pain resonance,
      possibly mediated by the human mirror-neuron system (hMNS). However, most of
      these studies have used stimuli that included emotional or cultural components,
      hence obscuring the precise contribution of physical similarity to resonance
      phenomena per se. The goal of the present study was to assess the effect of
      physical similarity (skin color) on motor resonance using stimuli that have no
      emotional and cultural components. We used both behavioral (imitation) and
      electrophysiological measures (mu-rhythm) to assess the effects of skin color on
      the hMNS during the observation of simple finger movements. Our results show
      that, in line with previous results, observation of biological movements resulted
      in faster reaction times and greater mu-rhythm suppression compared to non
      biological movements. However, physical similarity did not affect imitation speed
      or mu-rhythm desynchronization. These results suggest that physical similarity
      with an observed action in terms of skin color does not modulate hMNS activity,
      and that the enhanced resonance effects reported in the previous studies are
      likely attributable to cultural and emotional aspects. 

PMID- 23968691
TI  - Cloning of prophenoloxidase from hemocytes of the blue crab, Callinectes sapidus
      and its expression and enzyme activity during the molt cycle.
AB  - The arthropods cuticle undergoes dramatic morphological and biochemical changes
      from being soft to hardness through each molting process. Prophenoloxidase (PPO)
      known as a key enzyme in the arthropod innate immune system involved in the
      melanization reaction, has been related with the initial shell-hardening process,
      specifically in the sclerotization of the protein matrix in the new cuticle.
      Since hemocytes have been reported as the main PPO source in arthropods, the
      transport of hemocyte PPO into the newly laid, soft cuticle has been proposed for
      shell-hardening occurring during and immediately after ecdysis. In order to
      define the role of hemocyte PPO in the shell-hardening of crustaceans, the full
      length cDNA sequence (2806 nt) of hemocytes PPO of the blue crab Callinectes
      sapidus (CasPPO-hemo) is isolated using degenerate PCR and 5'-3' RACE. CasPPO
      hemo encodes a putative PPO (672 aa) showing three hemocyanin domains: N, M, and
      C in order and two copper binding sites (CuA & CuB). The sequence analysis
      identifies the putative CasPPO-hemo as zymogen which requires the cleavage at the
      N-terminus for its activation. Hemocyte extract (CasHLS) contains the PO, the
      activity of which depends on the in vitro activation of trypsin. The expression
      levels of CasPPO-hemo are kept constant during the molt cycle. The increase in
      the number of hemocytes at early premolt correlates with the elevated PO
      activity, while at late premolt, the increment in hemocyte numbers does not
      reflect on the PO activity. The functional importance of the changes in the
      levels of CasHLS-PO activity during molt cycle is discussed in relation to
      cuticle hardening process.

PMID- 23968690
TI  - Early event-related potentials indicate context-specific target processing for
      eye and hand motor systems.
AB  - Concurrent eye and hand movements toward a common visual target require different
      motor programs based on identical visual input. We used event-related brain
      potentials (ERP) to determine if and when the processing of the visual target
      differs for the two motor systems. The N2, an index for target evaluation, was
      more negative for the target of a hand than of an eye movement in two
      experiments. A possible interpretation for this finding is different visual
      target processing. Targets for hand movements require a different weighting of
      visual information, for example concerning features such as surface structure
      which are important for hand but not for eye movements. In experiment 2, the
      early C1-component, which had an average maximum at 67 ms following target onset,
      was significantly more negative when subjects pointed at the stimuli.
      Traditionally, the C1 has been regarded as a sensory component, but recent
      studies have linked it to higher order processing, such as attention and
      expectations. Thus, the present data indicate that target processing for eye or
      hand movements is already context-specific during early visual information
      processing. We suggest that differences in a target's relevance for upcoming
      movements modify target processing as well as sensory expectations.

PMID- 23968692
TI  - Genomic characterization, expression analysis, and antimicrobial function of a
      glyrichin homologue from rock bream, Oplegnathus fasciatus.
AB  - Antimicrobial peptides are important innate effector molecules, playing a vital
      role in antimicrobial immunity in all species. Glyrichin is a transmembrane
      protein and an antibacterial peptide, exerting its functions against a wide range
      of pathogenic bacteria. In this study, cDNA and a BAC clone harboring the
      glyrichin gene were identified from rock bream and characterized. Genomic
      characterization showed that the OfGlyrichin gene exhibited a 3 exon-2 intron
      structure. OfGlyrichin is a 79-amino-acid protein with a transmembrane domain at
      (22)GFMMGFAVGMAAGAMFGTFSCLR(44). Pairwise and multiple sequence alignments showed
      high identity and conservation with mammalian orthologues. Phylogenetic analysis
      showed a close relationship with fish species. Higher levels of OfGlyrichin
      transcripts were detected in the liver from healthy rock bream which were induced
      by immunogens like lipopolysaccharide, poly I:C, rock bream irido virus,
      Edwardsiella tarda and Streptococcus iniae. The synthetic peptide (pOf19) showed
      antibacterial activity against Escherichia coli, E. tarda, and S. iniae. Analysis
      of the bacterial morphological features after pOf19 peptide treatment showed
      breakage of the cell membrane, affirming that antibacterial function is
      accomplished through membrane lysis. The pOf19 peptide also showed antiviral
      activity against RBIV infection. The high conservation of the genomic structure
      and protein, together with the antimicrobial roles of OfGlyrichin, provide
      evidence for the evolutionary existence of this protein playing a vital role in
      innate immune defense in rock bream. 

PMID- 23968693
TI  - Agreement between patient interview data on prescription medication use and
      pharmacy records in those aged older than 50 years varied by therapeutic group
      and reporting of indicated health conditions.
AB  - OBJECTIVES: To estimate the agreement between interview-ascertained medication
      use and pharmacy records among the population aged older than 50 years, and to
      identify patient-level predictors of discordance. STUDY DESIGN AND SETTING: The
      Irish Longitudinal study on Ageing is representative of community-dwelling adults
      aged 50 years and older in Ireland. Interview-ascertained medication data from
      2,621 participants were linked to pharmacy dispensing records. The kappa
      statistics measured the agreement between the two sources for 19 therapeutic
      classes. Logistic regression assessed the effect of patient-level characteristics
      on survey under- and overreporting of regularly dispensed medications. RESULTS:
      Agreement was good or very good (kappa=0.64-0.86) for 15 medication classes, and
      moderate or poor for antiinflammatory and antirheumatic products (kappa=0.54),
      analgesics (kappa=0.50), psycholeptics (kappa=0.59), and ophthalmologicals
      (kappa=0.37). Not reporting an indicated health condition, less frequent
      dispensing, older age, and more medications regularly dispensed were associated
      with survey underreporting, but results varied by therapeutic class. Memory and
      cognition were not associated with discordance. CONCLUSION: Ascertaining
      medication use via patient interview seems a valid method for most medication
      classes and also captures nonprescription and supplement use. However,
      medications applied topically and as needed may be underreported. The source of
      medication data should be carefully considered when performing
      pharmacoepidemiological studies.

PMID- 23968694
TI  - Sugar for the brain: the role of glucose in physiological and pathological brain
      function.
AB  - The mammalian brain depends upon glucose as its main source of energy, and tight
      regulation of glucose metabolism is critical for brain physiology. Consistent
      with its critical role for physiological brain function, disruption of normal
      glucose metabolism as well as its interdependence with cell death pathways forms
      the pathophysiological basis for many brain disorders. Here, we review recent
      advances in understanding how glucose metabolism sustains basic brain physiology.
      We synthesize these findings to form a comprehensive picture of the cooperation
      required between different systems and cell types, and the specific breakdowns in
      this cooperation that lead to disease. 

PMID- 23968696
TI  - Comparative study of the effects of laser photobiomodulation and extract of
      Brassica oleracea on skin wounds in wistar rats: A histomorphometric study.
AB  - The objective of this study was to investigate the effect of a photobiomodulation
      laser and Brassica oleracea on tissue morphology in skin wounds. The parameters
      analyzed were type I and III collagen fibers, and thickness and surface density
      of the epithelial tissue, as well as how quickly the wound closed. Five skin
      wounds 12mm in diameter were made on the backs of the animals, which were
      randomized into four groups (8 animals each). Saline Group: 0.9% saline solution;
      Ointment Group (extract of Cabbage, B. oleracea, 10% lanolin); Balsam Group (10%
      glycolic extract of B. oleracea emulsion oil); L60 Group (laser GaAsAl
      60J/cm(2)). The applications were made daily during a 20-day treatment, and every
      4 days tissue from different wounds was removed. The reduction in the size of the
      wounds on the 4th, 8th, 12th and 16th days was significantly greater in the
      treated groups compared to the control group. At all the time points analyzed,
      there was a greater proportion of collagen in the Balsam and L60 groups (p<0.05).
      There was also a greater proliferation of epithelial cells in the L60 and Balsam
      groups after 20 days of treatment (p<0.05). The healing extract and laser
      60j/cm(2) exerted a great effect on collagen proliferation in stimulating scar
      tissue maturation. 

PMID- 23968695
TI  - NMNATs, evolutionarily conserved neuronal maintenance factors.
AB  - Proper brain function requires neuronal homeostasis over a range of environmental
      challenges. Neuronal activity, injury, and aging stress the nervous system, and
      lead to neuronal dysfunction and degeneration. Nevertheless, most organisms
      maintain healthy neurons throughout life, implying the existence of active
      maintenance mechanisms. Recent studies have revealed a key neuronal maintenance
      and protective function for nicotinamide mononucleotide adenylyl transferases
      (NMNATs). We review evidence that NMNATs protect neurons through multiple
      mechanisms in different contexts, and highlight functions that either require or
      are independent of NMNAT catalytic activity. We then summarize data supporting a
      role for NMNATs in neuronal maintenance and raise intriguing questions on how
      NMNATs preserve neuronal integrity and facilitate proper neural function
      throughout life. 

PMID- 23968697
TI  - Management of vascular access in transcatheter aortic valve replacement: part 2:
      Vascular complications.
AB  - The interventional cardiologist must be able to recognize and manage potential
      vascular complications. Iliofemoral complications are the most frequent vascular
      complications in transfemoral transcatheter aortic valve implantation. Small
      vessel dimensions, moderate or severe calcification, and center experience are
      the major predictors. The traditional treatment for injured arteries has been
      surgical reconstruction, but endovascular techniques may allow for less invasive
      but effective management of arterial injuries. Dissection may be treated with
      prolonged balloon inflation or deployment of a self-expanding or balloon
      expandable stent or a surgical graft. Iliofemoral rupture is a serious
      complication that may lead to retroperitoneal bleeding that can be unrecognized.
      Rapid insertion of a dilator or sheath or an occlusive balloon is used to achieve
      hemostasis. Prolonged balloon inflation or implantation of a covered stent or
      surgical repair should then be considered. Treatment options for failed
      percutaneous closure include prolonged manual compression, balloon angioplasty,
      stent implantation, and surgery. Aortic complications are rare, but serious
      complications are associated with a high mortality rate, even if emergent surgery
      is performed. There are specific vascular complications associated with
      alternative access routes such as transapical and transaxillary and direct aortic
      access. 

PMID- 23968698
TI  - Improved safety and reduction in stent thrombosis associated with biodegradable
      polymer-based biolimus-eluting stents versus durable polymer-based sirolimus
      eluting stents in patients with coronary artery disease: final 5-year report of
      the LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating)
      randomized, noninferiority trial.
AB  - OBJECTIVES: This study sought to report the final 5 years follow-up of the
      landmark LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating)
      trial. BACKGROUND: The LEADERS trial is the first randomized study to evaluate
      biodegradable polymer-based drug-eluting stents (DES) against durable polymer
      DES. METHODS: The LEADERS trial was a 10-center, assessor-blind, noninferiority,
      "all-comers" trial (N = 1,707). All patients were centrally randomized to
      treatment with either biodegradable polymer biolimus-eluting stents (BES) (n =
      857) or durable polymer sirolimus-eluting stents (SES) (n = 850). The primary
      endpoint was a composite of cardiac death, myocardial infarction (MI), or
      clinically indicated target vessel revascularization within 9 months. Secondary
      endpoints included extending the primary endpoint to 5 years and stent thrombosis
      (ST) (Academic Research Consortium definition). Analysis was by intention to
      treat. RESULTS: At 5 years, the BES was noninferior to SES for the primary
      endpoint (186 [22.3%] vs. 216 [26.1%], rate ratio [RR]: 0.83 [95% confidence
      interval (CI): 0.68 to 1.02], p for noninferiority <0.0001, p for superiority =
      0.069). The BES was associated with a significant reduction in the more
      comprehensive patient-orientated composite endpoint of all-cause death, any MI,
      and all-cause revascularization (297 [35.1%] vs. 339 [40.4%], RR: 0.84 [95% CI:
      0.71 to 0.98], p for superiority = 0.023). A significant reduction in very late
      definite ST from 1 to 5 years was evident with the BES (n = 5 [0.7%] vs. n = 19
      [2.5%], RR: 0.26 [95% CI: 0.10 to 0.68], p = 0.003), corresponding to a
      significant reduction in ST-associated clinical events (primary endpoint) over
      the same time period (n = 3 of 749 vs. n = 14 of 738, RR: 0.20 [95% CI: 0.06 to
      0.71], p = 0.005). CONCLUSIONS: The safety benefit of the biodegradable polymer
      BES, compared with the durable polymer SES, was related to a significant
      reduction in very late ST (>1 year) and associated composite clinical outcomes.
      (Limus Eluted From A Durable Versus ERodable Stent Coating [LEADERS] trial;
      NCT00389220).

PMID- 23968699
TI  - Enhanced mortality risk prediction with a focus on high-risk percutaneous
      coronary intervention: results from 1,208,137 procedures in the NCDR (National
      Cardiovascular Data Registry).
AB  - OBJECTIVES: This study sought to update and validate a contemporary model for
      inpatient mortality following percutaneous coronary intervention (PCI), including
      variables indicating high clinical risk. BACKGROUND: Recently, new variables were
      added to the CathPCI Registry data collection form. This modification allowed us
      to better characterize the risk of death, including recent cardiac arrest and
      duration of cardiogenic shock. METHODS: Data from 1,208,137 PCI procedures
      performed between July 2009 and June 2011 at 1,252 CathPCI Registry sites were
      used to develop both a "full" and pre-catheterization PCI in-hospital mortality
      risk model using logistic regression. To support prospective implementation, a
      simplified bedside risk score was derived from the pre-catheterization risk
      model. Model performance was assessed by discrimination and calibration metrics
      in a separate split sample. RESULTS: In-hospital mortality was 1.4%, ranging from
      0.2% among elective cases (45.1% of total cases) to 65.9% among patients with
      shock and recent cardiac arrest (0.2% of total cases). Cardiogenic shock and
      procedure urgency were the most predictive of inpatient mortality, whereas the
      presence of a chronic total occlusion, subacute stent thrombosis, and left main
      lesion location were significant angiographic predictors. The full, pre
      catheterization, and bedside risk prediction models performed well in the overall
      validation sample (C-indexes 0.930, 0.928, 0.925, respectively) and among pre
      specified patient subgroups. The model was well calibrated across the risk
      spectrum, although slightly overestimating risk in the highest risk patients.
      CONCLUSIONS: Clinical acuity is a strong predictor of PCI procedural mortality.
      With inclusion of variables that further characterize clinical stability, the
      updated CathPCI Registry mortality models remain well-calibrated across the
      spectrum of PCI risk.

PMID- 23968700
TI  - Radial versus femoral access for primary percutaneous interventions in ST-segment
      elevation myocardial infarction patients: a meta-analysis of randomized
      controlled trials.
AB  - OBJECTIVES: This study sought to determine the safety and efficacy of radial
      access compared with femoral access for primary percutaneous coronary
      intervention (PCI) in patients with ST-segment elevation myocardial infarction
      (STEMI). BACKGROUND: Numerous randomized controlled trials, including several new
      studies, have compared outcomes of these approaches in the context of primary PCI
      for STEMI patients with inconclusive results. METHODS: We performed a meta
      analysis of randomized controlled trials to compare outcomes in STEMI patients
      undergoing radial versus femoral access for primary PCI. Primary outcomes were
      death and major bleeding evaluated at the longest available follow-up. Secondary
      outcomes included access site bleeding, stroke, and procedure time. Twelve
      studies (N = 5,055) were included. All trials were conducted in centers
      experienced with both approaches. RESULTS: Compared with femoral approach, radial
      approach was associated with decreased risk of mortality (2.7% vs. 4.7%; odds
      ratio [OR]: 0.55, 95% confidence interval [CI]: 0.40 to 0.76; p < 0.001) and
      decreased risk of major bleeding (1.4% vs. 2.9%; OR: 0.51, 95% CI: 0.31 to 0.85;
      p = 0.01). Radial access was also associated with reduction in relative risk of
      access site bleeding (2.1% vs. 5.6%; OR: 0.35, 95% CI: 0.25 to 0.50; p < 0.001).
      Stroke risk was similar between both approaches (0.5% vs. 0.5%; OR: 1.07, 95% CI:
      0.45 to 2.54; p = 0.87). The procedure time was slightly longer in the radial
      group than in the femoral group (mean difference: 1.52 min; 95% CI: 0.33 to 2.70,
      p = 0.01). CONCLUSIONS: In STEMI patients undergoing primary PCI, the radial
      approach is associated with favorable outcomes and should be the preferred
      approach for experienced radial operators.

PMID- 23968701
TI  - Radial access for ST-segment elevation myocardial infarction interventions: does
      it really lower mortality?

PMID- 23968702
TI  - The value proposition in percutaneous coronary intervention.

PMID- 23968703
TI  - Clinical implications of very low on-treatment platelet reactivity in patients
      treated with thienopyridine: the POBA study (predictor of bleedings with
      antiplatelet drugs).
AB  - OBJECTIVES: This study was designed to define the hyperresponse to thienopyridine
      (very low on-treatment platelet reactivity [VLTPR]) as the most predictive
      threshold value of platelet reactivity index vasodilator-stimulated
      phosphoprotein (PRI VASP) for the prediction of non-access site-related bleeding
      events. We also aimed to identify predictors of bleeding and VLTPR in patients
      treated with thienopyridines. BACKGROUND: New P2Y12 blockers and platelet
      monitoring has been proposed to optimize platelet inhibition after acute coronary
      syndromes and improve ischemic outcomes. However, bleeding complications remain
      the Achilles' heel of antiplatelet therapy, and platelet monitoring could be
      useful to evaluate this risk. METHODS: A total of 1,542 consecutive patients
      undergoing coronary stenting for ACS were included in the present study (287
      taking clopidogrel 75 mg, 868 taking clopidogrel 150 mg, and 387 taking prasugrel
      10 mg). RESULTS: During 6-month follow-up, 9% of patients (n = 139) experienced
      nonaccess site-related Bleeding Academic Research Consortium bleeding
      complications. These patients were more often women and nondiabetic and had lower
      PRI VASP values than others (p < 0.001). Receiver-operating characteristic curve
      analysis (0.71, p < 0.01) identified a threshold value for VLTPR of PRI VASP
      <=10% to predict bleeding events with a sensitivity of 17% and a specificity of
      97%. Although prasugrel was the main predictor of VLTPR in the whole population
      (odds ratio: 10.2, 95% confidence interval: 3.0 to -34.2; p < 0.001), VLTPR was
      the strongest and independent predictor of bleeding (odds ratio: 4.7, 95%
      confidence interval: 2.7 to 8.3; p < 0.001). CONCLUSIONS: The present study
      identified VLTPR (PRI VASP <=10%) as the strongest predictor of bleeding
      complications in patients treated with thienopyridines. This marker could be
      useful for tailored therapy and bleeding prevention.

PMID- 23968704
TI  - Bleeding and thrombosis risk matters: how long can we stick to the one-size-fits
      all strategy of platelet inhibition?

PMID- 23968705
TI  - Survival after endovascular therapy in patients with type B aortic dissection: a
      report from the International Registry of Acute Aortic Dissection (IRAD).
AB  - OBJECTIVES: This study sought to evaluate long-term survival in type B aortic
      dissection patients treated with thoracic endovascular aortic repair (TEVAR)
      therapy. BACKGROUND: Historical data have supported medical therapy in type B
      acute aortic dissection (TBAAD) patients. Recent advances in TEVAR appear to
      improve in-hospital mortality. METHODS: We examined 1,129 consecutive patients
      with TBAAD enrolled in IRAD (International Registry of Acute Aortic Dissection)
      between 1995 and 2012 who received medical (n = 853, 75.6%) or TEVAR (n = 276,
      24.4%) therapy. RESULTS: Clinical history was similar between groups. TEVAR
      patients were more likely to present with a pulse deficit (28.3% vs. 13.4%, p <
      0.001) and lower extremity ischemia (16.8% vs. 3.6%, p < 0.001), and to
      characterize their pain as the "worst pain ever" (27.5% vs. 15.7%, p < 0.001).
      TEVAR patients were also most likely to present with complicated acute aortic
      dissection, defined as shock, periaortic hematoma, signs of malperfusion, stroke,
      spinal cord ischemia, mesenteric ischemia, and/or renal failure (61.7% vs.
      37.2%). In-hospital mortality was similar in patients managed with endovascular
      repair (10.9% vs. 8.7%, p = 0.273) compared with medically managed patients. One
      year mortality was also similar in both groups (8.1% endovascular vs. 9.8%
      medical, p = 0.604). Among adverse events during follow-up, aortic growth/new
      aneurysm was most common, occurring in 73.3% of patients with medical therapy and
      in 62.7% of patients after TEVAR, based on 5-year Kaplan-Meier estimates. Kaplan
      Meier survival estimates showed that patients undergoing TEVAR had a lower death
      rate (15.5% vs. 29.0%, p = 0.018) at 5 years. CONCLUSIONS: Results from IRAD show
      that TEVAR is associated with lower mortality over a 5-year period than medical
      therapy for TBAAD. Further randomized trials with long-term follow-up are needed.

PMID- 23968706
TI  - Tissue uptake, distribution, and healing response after delivery of paclitaxel
      via second-generation iopromide-based balloon coating: a comparison with the
      first-generation technology in the iliofemoral porcine model.
AB  - OBJECTIVES: This study sought to evaluate vascular drug uptake, distribution and
      response of second-generation paclitaxel coated balloon (PCB) (Cotavance, MEDRAD
      Interventional, Indianola, Pennsylvania) and compare it with first-generation
      technology, containing identical excipient and drug concentration. BACKGROUND:
      Original PCB technologies displayed a heterogeneous deposition of crystalline
      paclitaxel-iopromide inside the balloon folds, whereas second-generation PCBs
      consisted of more homogeneous, circumferential coatings. METHODS: Paclitaxel
      tissue uptake was assessed in 20 iliofemoral arteries of a domestic swine.
      Vascular healing response was assessed in the familial hypercholesterolemic model
      of iliofemoral in-stent restenosis. Three weeks after bare-metal stent
      implantation, vascular segments were randomly revascularized with first
      generation PCBs (n = 6), second-generation PCBs (n = 6), or plain balloon
      angioplasty (PBA) (n = 6). At 28 days, angiographic and histological evaluation
      was performed in all treated segments. RESULTS: One-hour paclitaxel tissue uptake
      was 42% higher in the second-generation PCBs (p = 0.03) and resulted in more
      homogeneous segment-to-segment distribution compared with first-generation PCBs.
      Both angiography (percentage of diameter stenosis: second-generation 11.5 +/- 11%
      vs. first-generation 21.9 +/- 11% vs. PBA 46.5 +/- 10%; p < 0.01) and histology
      (percentage of area stenosis: second-generation 50.5 +/- 7% vs. first-generation
      54.8 +/- 18% vs. PBA 78.2 +/- 9%; p < 0.01) showed a decrease in neointimal
      proliferation in both PCB groups. Histological variance of the percentage of area
      stenosis was lower in second-generation compared with first-generation PCBs (51.7
      vs. 328.3; p = 0.05). The presence of peristrut fibrin deposits (0.5 vs. 2.4; p <
      0.01) and medial smooth muscle cell loss (0 vs. 1.7; p < 0.01) were lower in the
      second-generation compared with first-generation PCBs. CONCLUSIONS: In the
      experimental setting, second-generation PCB showed a comparable efficacy profile
      and more favorable vascular healing response when compared to first-generation
      PCB. The clinical implications of these findings require further investigation.

PMID- 23968707
TI  - Quantitative optical coherence tomography tissue-type imaging for lipid-core
      plaque detection.

PMID- 23968708
TI  - A new tool to manage side-branch occlusion after covered-stent implantation for
      vascular complications: the neocarina reconstruction technique.

PMID- 23968709
TI  - The case for live case demonstrations.

PMID- 23968710
TI  - Hepatic brucellar abscess.

PMID- 23968711
TI  - Design, synthesis and biological evaluation of novel mansonone E derivatives
      prepared via CuAAC click chemistry as topoisomerase II inhibitors.
AB  - Two series of novel C-9 chloro- and bromo-substituted mansonone E derivatives
      with triazole moieties at the C-3 position were prepared by using copper
      catalysed azide-alkyne cycloaddition click chemistry. These compounds were found
      as potent inhibitors of topoisomerase II (Topo II) and topoisomerase I (Topo I).
      The Topo II-mediated pBR322 DNA relaxation and cleavage assay showed that the
      derivatives might act as catalytic inhibitors. Their cytotoxic activities against
      A549, HL-60, K562 and HeLa cells were evaluated, indicating that these compounds
      were potent antitumour agents. Their structure activity relationships and
      molecular docking study revealed that the substituents of the triazole were
      particularly important for cytotoxicity. 

PMID- 23968712
TI  - Studying effects of weather parameters on acute stroke: considering the
      contribution of "risk factors" and "triggering factors" together.

PMID- 23968713
TI  - Non-invasive assessment of microvascular dysfunction in families with premature
      coronary artery disease.

PMID- 23968714
TI  - Functional iron deficiency and diastolic function in heart failure with preserved
      ejection fraction.
AB  - BACKGROUND: Functional iron deficiency (FID) is an independent risk factor for
      poor outcome in advanced heart failure with reduced EF, but its role in heart
      failure with preserved EF (HFPEF) remains unclear. We aimed to investigate the
      impact of FID on cardiac performance determined by pressure-volume loop analysis
      in HFPEF. METHODS: 26 HFPEF patients who showed an increase in LV stiffness by
      pressure-volume (PV) loop analysis obtained by conductance-catheterization,
      performed exercise testing, echocardiographic examination including tissue
      Doppler and determination of iron metabolism: serum iron, ferritin and
      transferrin saturation. HFPEF patients who provided ferritin <100 MUg/l or
      ferritin of 100-299 MUg/l in combination with transferrin saturation <20% were
      defined as having FID. In 14 patients the expression of transferrin receptor was
      determined from available endomyocardial biopsies. RESULTS: Fifteen out of 26
      HFPEF patients showed FID without anemia. Compared to control subjects and HFPEF
      patients without FID, HFPEF patients with FID showed an up-regulation of the
      myocardial transferrin receptor expression (p<0.05). No differences between HFPEF
      patients with and without iron deficiency were found in heart dimensions,
      systolic and diastolic function obtained by PV-loop and echocardiography
      analysis. According to the linear regression analysis, LV stiffness was
      correlated with peak oxygen uptake (r=-0.636, p<0.001) but not with the ferritin
      level or transferrin saturation. No relation was found between FID and exercise
      capacity. The association of LV stiffness with exercise performance was
      independent from the level of iron deficiency. CONCLUSION: In non-anemic HFPEF
      patients, cardiac dysfunction and impaired exercise capacity occur independently
      of FID.

PMID- 23968715
TI  - Similar effects of vagus nerve stimulation and atrial ganglionated plexi
      stimulation on ventricular effective refractory period and action potential
      duration in canine.

PMID- 23968716
TI  - The relevance of the brain in the diseased heart: authors' response.

PMID- 23968717
TI  - Reply to the letter by Ando et al.

PMID- 23968718
TI  - Effects of Ivabradine on left ventricular function in patients with ischemic
      heart disease.

PMID- 23968719
TI  - Development of a single multiplex amplification refractory mutation system PCR
      for the detection of rifampin-resistant Mycobacterium tuberculosis.
AB  - A rapid and simple method for the detection of drug-resistant Mycobacterium
      tuberculosis is critical for the efficient treatment and control of this pathogen
      in developing country. Here we developed a single multiplex amplification
      refractory mutation system (M-ARMS) PCR, in which chimeric-primer and temperature
      switch PCR (TSP) strategy were included. Using this method, we detected rifampin
      resistance-associated mutations at codons 511, 516, 526 and 531 in the rifampin
      resistance-determining region of rpoB gene. The performance of M-ARMS-PCR assay
      was evaluated with 135 cultured isolates of M. tuberculosis. The sensitivity and
      specificity were 94.2% and 100%, respectively, compared with direct DNA
      sequencing, and 86.67% and 89.71%, respectively, compared with culture-based
      phenotypic drug susceptibility testing. Therefore, this newly-developed M-ARMS
      PCR method is useful and efficient with an intended application in provincial
      Centers for Disease Control and Prevention for rapid detection of rifampin
      resistance-associated mutations. 

PMID- 23968721
TI  - Serologic survey of plague in animals, Western Iran.

PMID- 23968720
TI  - Attenuation of fibroblast growth factor signaling by poly-N-acetyllactosamine
      type glycans.
AB  - Fibroblast growth factors (FGFs) and their receptors are expressed in a variety
      of mammalian tissues, playing a role in development and cell proliferation. While
      analyzing human sperm motility, we found that sperm treated with endo-beta
      galactosidase (EBG), which specifically hydrolyzes poly-N-acetyllactosamine type
      glycans (polyLacs), enhanced motility. Mass spectrometry analysis revealed that
      sperm-associated polyLacs are heavily fucosylated, consistent with Lewis Y
      antigen. Immunohistochemistry of epididymis using an anti-Lewis Y antibody before
      and after EBG treatment suggested that polyLacs carrying the Lewis Y epitope are
      synthesized in epididymal epithelia and secreted to seminal fluid. EBG-treated
      sperm elevated cAMP levels and calcium influx, indicating activation of
      fibroblast growth factor signaling. Seminal fluid polyLacs bound to FGFs in
      vitro, and impaired FGF-mediated signaling in HEK293T cells. 

PMID- 23968722
TI  - Synchronized 2D/3D optical mapping for interactive exploration and real-time
      visualization of multi-function neurological images.
AB  - Efficient software with the ability to display multiple neurological image
      datasets simultaneously with full real-time interactivity is critical for brain
      disease diagnosis and image-guided planning. In this paper, we describe the
      creation and function of a new comprehensive software platform that integrates
      novel algorithms and functions for multiple medical image visualization,
      processing, and manipulation. We implement an opacity-adjustment algorithm to
      build 2D lookup tables for multiple slice image display and fusion, which
      achieves a better visual result than those of using VTK-based methods. We also
      develop a new real-time 2D and 3D data synchronization scheme for multi-function
      MR volume and slice image optical mapping and rendering simultaneously through
      using the same adjustment operation. All these methodologies are integrated into
      our software framework to provide users with an efficient tool for flexibly,
      intuitively, and rapidly exploring and analyzing the functional and anatomical MR
      neurological data. Finally, we validate our new techniques and software platform
      with visual analysis and task-specific user studies. 

PMID- 23968723
TI  - Draft genome sequence of the cellulolytic Clostridium thermocellum wild-type
      strain BC1 playing a role in cellulosic biomass degradation.
AB  - The bacterium Clostridium thermocellum BC1, a thermophilic, anaerobic bacterium
      of the family Clostridiaceae, was isolated from a compost treatment site in
      Germany. It is able to grow efficiently on cellulose and cellodextrins. The draft
      genome sequence of C. thermocellum BC1 has been established and provides the
      genetic basis for application of this microorganism in thermophilic degradation
      of cellulosic biomass. 

PMID- 23968724
TI  - Multimeric immobilization of alcohol oxidase on electrospun fibers for valid
      tests of alcoholic saliva.
AB  - An accurate quantitation of ethanol is of great importance in clinical and
      forensic analyses. In the current study, alcohol oxidase (AOX) from Pichia
      pastoris, a multimeric enzyme consisting of eight identical subunits, was
      immobilized on electrospun polystyrene-co-maleic anhydride (PSMA) fibers for
      valid tests of alcoholic saliva. Branched polyethyleneimine (PEI) was grafted on
      PSMA fibers with a density of 0.15 nmol/cm(2) as tethers to allow multipoint
      covalent binding of enzyme molecules through glutaraldehyde activation, and the
      secondary and tertiary amino groups of PEI could intensify the interactions with
      AOX subunits to stabilize the quaternary structure. PSMA-PEI-AOX fibers were less
      sensitive than free AOX to the incubation temperature and pH, and indicated no
      detectable subunit release from the immobilized AOX after boiling in the presence
      of sodium dodecyl sulfate (SDS) and 2-mercaptoethanol. Color strips were
      established on PSMA-PEI-AOX fibrous mats dyed with indigo Carmine after
      incubation into ethanol solutions of different concentrations. The color fading
      ratio remained no significant change after repeat tests for 9 cycles after
      immersion in 0.2 and 0.8 mg/mL of alcoholic saliva. It was indicated that
      multipoint immobilization of the multimeric enzyme was essential to improve the
      enzyme stability by stabilizing both the quaternary structure of the enzyme and
      the structure of each individual subunit.

PMID- 23968725
TI  - Arsenic induces the expressions of angiogenesis-related factors through PI3K and
      MAPK pathways in SV-HUC-1 human uroepithelial cells.
AB  - Arsenic, a well-established human carcinogen, can cause various types of cancers,
      including bladder cancer. Angiogenesis is a key event for tumor initiation. In
      this study, several important angiogenesis related factors, including
      cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and hypoxia
      inducible factor-1alpha (HIF-1alpha), were up-regulated and PI3K/AKT and MAPK
      signal pathways were activated in human uroepithelial cell line (SV-HUC-1)
      treated with NaAsO2 (0, 1, 2, 4, 8 or 10MUM) for 24h. Arsenite-induced HIF
      1alpha, VEGF and COX-2 expressions were decreased by PI3K inhibitors. Blockage of
      the ERK1/2, p38 and JNK down-regulated the VEGF level, while ERK1/2 and p38
      inhibitors were more effective than JNK in attenuating arsenite-induced COX-2
      expression. HIF-1alpha expression was only decreased by ERK1/2 inhibitor. It was
      found that superoxide (O2(-)) generation was involved in arsenite-induced the
      activation of MAPK and PI3K pathways, which led to the HIF-1alpha, COX-2 and VEGF
      overexpressions. In conclusion, arsenite-induced COX-2, VEGF and HIF-1alpha
      expressions, mediated partially by reactive oxygen species (ROS), were regulated
      by MAPK and PI3K/AKT signaling pathways in human uroepithelial cells. 

PMID- 23968726
TI  - Global DNA methylation screening of liver in piperonyl butoxide-treated mice in a
      two-stage hepatocarcinogenesis model.
AB  - Disruptive epigenetic gene control has been shown to be involved in
      carcinogenesis. To identify key molecules in piperonyl butoxide (PBO)-induced
      hepatocarcinogenesis, we searched hypermethylated genes using CpG island (CGI)
      microarrays in non-neoplastic liver cells as a source of proliferative lesions at
      25 weeks after tumor promotion with PBO using mice. We further performed
      methylation-specific polymerase chain reaction (PCR), real-time reverse
      transcription PCR, and immunohistochemical analysis in PBO-promoted liver
      tissues. Ebp4.1, Wdr6 and Cmtm6 increased methylation levels in the promoter
      region by PBO promotion, although Cmtm6 levels were statistically non
      significant. These results suggest that PBO promotion may cause altered
      epigenetic gene regulation in non-neoplastic liver cells surrounding
      proliferative lesions to allow the facilitation of hepatocarcinogenesis. Both
      Wdr6 and Cmtm6 showed decreased expression in non-neoplastic liver cells in
      contrast to positive immunoreactivity in the majority of proliferative lesions
      produced by PBO promotion. These results suggest that both Wdr6 and Cmtm6 were
      spared from epigenetic gene modification in proliferative lesions by PBO
      promotion in contrast to the hypermethylation-mediated downregulation in
      surrounding liver cells. Considering the effective detection of proliferative
      lesions, these molecules could be used as detection markers of hepatocellular
      proliferative lesions and played an important role in hepatocarcinogenesis. 

PMID- 23968727
TI  - Hyper-methylated miR-203 dysregulates ABL1 and contributes to the nickel-induced
      tumorigenesis.
AB  - Nickel compounds have been found to be carcinogenic based upon epidemiological,
      animal and cell culture studies. Previous studies suggest that epigenetic
      mechanisms play a role in Nickel-induced carcinogenesis such as DNA methylation
      and histone modification. In this study, we investigated the role of microRNAs
      (miRNAs) in nickel-induced carcinogenesis. The expression of several miRNAs which
      may function as tumor suppressor genes revealed a strong downregulation of miR
      203 in Ni3S2-transformed 16HBE cells (NSTCs). Meanwhile, we observed
      hypermethylation of CpGs in miR-203 promoter and first exon area, and proved that
      the hyper-methylated miR-203 was involved in the Nickel-induced tumorigenesis.
      Moreover, we identified that miR-203 may suppress the tumorigenesis at least in
      part through negatively regulating its target gene ABL1. Our findings indicate
      that DNA methylation-associated silencing of tumor suppressor miRNAs contributes
      to the development of Nickel-induced cancer. 

PMID- 23968728
TI  - Highly specific and sensitive non-enzymatic determination of uric acid in serum
      and urine by extended gate field effect transistor sensors.
AB  - A potentiometric non-enzymatic sensor using off-chip extended-gate field effect
      transistor (EGFET) with a ferrocenyl-alkanethiol modified gold electrode is
      demonstrated for determining the uric acid concentration in human serum and
      urine. Hexacyanoferrate (II) and (III) ions are used as redox reagent. This
      potentiometric sensor measures the interface potential on the ferrocene
      immobilized gold electrode, which is modulated by the redox reaction between uric
      acid and hexacyanoferrate ions. The device shows a near Nernstian response to
      uric acid and is highly specific. The interference that comes from glucose,
      bilirubin, ascorbic acid and hemoglobin is negligible in normal concentration
      range of these interferents. The sensor also exhibits excellent long term
      reliability. This extended gate field effect transistor based sensors can be used
      as a point of care UA testing tool, due to the small size, low cost, and low
      sample volume consumption. 

PMID- 23968729
TI  - Label-free chemiluminescent ATP aptasensor based on graphene oxide and an
      instantaneous derivatization of guanine bases.
AB  - In this work, a novel label-free chemiluminescent (CL) aptasensor has been
      developed for rapid and facile detection of adenosine triphosphate (ATP, as model
      analyte) using graphene oxide (GO) nano-platform. The strategy relies on the
      preferential binding of GO to single-stranded DNA (ssDNA) over rigid double
      stranded DNA (dsDNA) or aptamer-target complexes, and the instantaneous
      derivative reaction between phenylglyoxal (PGO), a special CL reagent as the
      signaling molecule, and guanine nucleobases (G) of aptamer strands adsorbed on
      the surface of GO. In the absence of ATP, the aptamers adsorbed onto the surface
      of GO leading to a strong background CL signal. Conversely, in the presence of
      ATP, the aptamers formed the aptamer-ATP complexes which had weak binding ability
      to GO resulting in a significant CL signal decrease. The CL intensity was
      adversely related to the ATP concentration in the assay solution. The biosensor's
      signal decreased linearly with the logarithm of the concentration of ATP from 2
      to 80 nmol with a detection limit of 1.4 nmol. The aptasensor also showed high
      selectivity against cytosine triphosphate (CTP), guanosine triphosphate (GTP),
      and uridine triphosphate (UTP). The method presented here holds the advantages of
      being label-free, cost effective, rapid, sensitive and selective, which would
      shows great promise for clinical application.

PMID- 23968730
TI  - The requirements of a specialist Breast Centre.
AB  - INTRODUCTION: In recognition of the advances and evidence based changes in
      clinical practice that have occurred in recent years and taking into account the
      knowledge and experience accumulated through the voluntary breast unit
      certification programme, Eusoma has produced this up-dated and revised guidelines
      on the requirements of a Specialist Breast Centre (BC). METHODS: The content of
      these guidelines is based on evidence from the recent relevant peer reviewed
      literature and the consensus of a multidisciplinary team of European experts. The
      guidelines define the requirements for each breast service and for the
      specialists who work in specialist Breast Centres. RESULTS: The guidelines
      identify the minimum requirements needed to set up a BC, these being an
      integrated Breast Centre, dealing with a sufficient number of cases to allow
      effective working and continuing expertise, dedicated specialists working with a
      multidisciplinary approach, providing all services throughout the patients
      pathway and data collection and audit. It is essential that the BC also
      guarantees the continuity of care for patients with advanced (metastatic) disease
      offering treatments according to multidisciplinary competencies and a high
      quality palliative care service. The BC must ensure that comprehensive support
      and expertise may be needed, not only through the core BC team, but also ensure
      that all other medical and paramedical expertise that may be necessary depending
      on the individual case are freely available, referring the patient to the
      specific care provider depending on the problem. CONCLUSIONS: Applying minimum
      requirements and quality indicators is essential to improve organisation,
      performance and outcome in breast care. Efficacy and compliance have to be
      constantly monitored to evaluate the quality of patient care and to allow
      appropriate corrective actions leading to improvements in patient care.

PMID- 23968731
TI  - Clinical efficacy of second generation tyrosine kinase inhibitor and 5
      azacytidine combination in chronic myelogenous leukaemia in myeloid blast crisis.
AB  - Even in the tyrosine kinase inhibitors era, the prognosis of patients with
      chronic myeloid leukaemia in myeloid blast crisis remains dismal with few
      patients surviving longer than 6 months. Here we report the cases of 5 patients
      treated with the combination of 5-azacytidine and tyrosine kinase inhibitors for
      myeloid blast crisis CML. All patients achieved a complete haematological
      response including two with a complete cytogenetic and major molecular response.
      Two patients underwent an allogeneic stem cell transplantation. One died from
      relapse 34 months from diagnosis. The second is alive and free from disease at 11
      months from diagnosis. The other 3 patients are still in complete haematological
      response after 15, 24 and 33 months of follow-up. These results suggest that the
      combination has a significant activity in myeloid blast crisis and may increase
      survival.

PMID- 23968732
TI  - Pretreatment anti-Mullerian hormone predicts for loss of ovarian function after
      chemotherapy for early breast cancer.
AB  - AIM: Improving survival for women with early breast cancer (eBC) requires greater
      attention to the consequences of treatment, including risk to ovarian function.
      We have assessed whether biochemical markers of the ovarian reserve might improve
      prediction of chemotherapy related amenorrhoea. METHODS: Women (n=59, mean age
      42.6 years [(range 23.3-52.5]) with eBC were recruited before any treatment.
      Pretreatment ovarian reserve markers (anti-Mullerian hormone [AMH], follicle
      stimulating hormone [FSH], inhibin B) were analysed in relation to ovarian status
      at 2 years. RESULTS: Pretreatment AMH was significantly lower in women with
      amenorrhoea at 2 years (4.0 +/- 0.9 pmol/L versus 17.2 +/- 2.5, P<0.0001), but
      FSH and inhibin B did not differ between groups. By logistic regression,
      pretreatment AMH, but not age, FSH or inhibin B, was an independent predictor of
      ovarian status at 2 years (P=0.005; odds ratio 0.013). We combined these data
      with a similar cohort (combined n=75); receiver-operator characteristic analysis
      for AMH gave area under curve (AUC) of 0.90 (95% confidence interval (CI) 0.82
      0.97)). A cross-validated classification tree analysis resulted in a binary
      classification schema with sensitivity 98.2% and specificity 80.0% for correct
      classification of amenorrhoea. CONCLUSION: Pretreatment AMH is a useful predictor
      of long term post chemotherapy loss of ovarian function in women with eBC, adding
      significantly to the only previously established individualising predictor, i.e.
      age. AMH measurement may assist decision-making regarding treatment options and
      fertility preservation procedures.

PMID- 23968733
TI  - Increased expression of miR-126 and miR-10a predict prolonged relapse-free time
      of primary oestrogen receptor-positive breast cancer following tamoxifen
      treatment.
AB  - BACKGROUND: Adjuvant tamoxifen is a valid treatment option for women with
      oestrogen receptor (ER)-positive breast cancer. However, up to 40% of patients
      experience distant or local recurrence or die. MicroRNAs have been suggested to
      be important prognosticators in breast cancer. This study aims to identify
      microRNAs with the potential to predict tamoxifen response. PATIENTS AND METHODS:
      We performed a global microRNA screen (1105 human microRNAs) in primary tumours
      of six matched pairs of postmenopausal, ER-positive breast cancer patients
      treated with tamoxifen, who were either recurrence free or had developed a
      recurrence (median follow up: 8.84 years; range: 1.28-12.7 years). Patients of
      this discovery set and the 81 patients of the validation set (median follow up:
      8.64 years; range: 0.21-19.85 years) were treated at the Robert Bosch Hospital,
      Stuttgart, Germany, between 1986 and 2005. RESULTS: Out of the top 20 deregulated
      microRNAs (12 up-regulated, eight down-regulated) miR-126 (Hazard Ratio (HR) =
      0.56, 95% confidence interval (CI): 0.38-0.83; Holm-adj. P = 0.022) and miR-10a
      (HR = 0.53, 95% CI: 0.33-0.85; Holm-adj. P = 0.031) were identified as
      significant predictors of tamoxifen outcome by multivariate Cox regression
      analysis in the independent validation set of 81 postmenopausal, ER-positive
      patients. Kaplan-Meier survival analyses based on cut-offs determined by receiver
      operating characteristics curves confirmed that a higher expression of miR-126
      and miR-10a in the patients tumour was associated with longer relapse-free time
      (log-rank P = 0.037, P<0.0001, respectively). CONCLUSIONS: Our data suggest that
      miR-126 and miR-10a are independent predictors for tumour relapse in early
      postmenopausal breast cancer patients treated with adjuvant tamoxifen.

PMID- 23968734
TI  - miR-133a represses tumour growth and metastasis in colorectal cancer by targeting
      LIM and SH3 protein 1 and inhibiting the MAPK pathway.
AB  - In recent studies of microRNA expression, miR-133a deregulation was identified in
      colorectal carcinoma (CRC). However, the mechanisms underlying the pathogenesis
      and progression of CRC are poorly understood. We found that miR-133a expression
      was usually down-regulated in CRC cell lines and tissue specimens. Ectopic miR
      133a expression inhibited cell proliferation and cell migration. Stable
      overexpression of miR-133a was sufficient to suppress tumour growth and
      intrahepatic and pulmonary metastasis in vivo. Additional studies showed that miR
      133a can target the 3' untranslated region (3'UTR) of LIM and SH3 protein 1
      (LASP1) mRNA and suppress the expression of LASP1, which we identified in
      previous studies as a CRC-associated protein. In contrast to the phenotypes
      induced by miR-133a restoration, LASP1-induced cell proliferation and migration
      rescued miR-133a-mediated biological behaviours, as did LASP1 overexpression.
      Investigations of possible mechanisms underlying these behaviours revealed that
      miR-133a modulates the expression of key cellular molecules and participates in
      the MAPK pathway by inhibiting phosphorylation of ERK and MEK. miR-133a may play
      a key role in CRC genesis and metastasis, which suggests its potential role in
      the molecular therapy of cancer. 

PMID- 23968737
TI  - A framework for managing runoff and pollution in the rural landscape using a
      Catchment Systems Engineering approach.
AB  - Intense farming plays a key role in increasing local scale runoff and erosion
      rates, resulting in water quality issues and flooding problems. There is
      potential for agricultural management to become a major part of improved
      strategies for controlling runoff. Here, a Catchment Systems Engineering (CSE)
      approach has been explored to solve the above problem. CSE is an interventionist
      approach to altering the catchment scale runoff regime through the manipulation
      of hydrological flow pathways throughout the catchment. By targeting hydrological
      flow pathways at source, such as overland flow, field drain and ditch function, a
      significant component of the runoff generation can be managed in turn reducing
      soil nutrient losses. The Belford catchment (5.7 km(2)) is a catchment scale
      study for which a CSE approach has been used to tackle a number of environmental
      issues. A variety of Runoff Attenuation Features (RAFs) have been implemented
      throughout the catchment to address diffuse pollution and flooding issues. The
      RAFs include bunds disconnecting flow pathways, diversion structures in ditches
      to spill and store high flows, large wood debris structure within the channel,
      and riparian zone management. Here a framework for applying a CSE approach to the
      catchment is shown in a step by step guide to implementing mitigation measures in
      the Belford Burn catchment. The framework is based around engagement with
      catchment stakeholders and uses evidence arising from field science. Using the
      framework, the flooding issue has been addressed at the catchment scale by
      altering the runoff regime. Initial findings suggest that RAFs have functioned as
      designed to reduce/attenuate runoff locally. However, evidence suggested that
      some RAFs needed modification and new RAFs be created to address diffuse
      pollution issues during storm events. Initial findings from these modified RAFs
      are showing improvements in sediment trapping capacities and reductions in
      phosphorus, nitrate and suspended sediment losses during storm events.

PMID- 23968736
TI  - Segmentation of neonatal brain MR images using patch-driven level sets.
AB  - The segmentation of neonatal brain MR image into white matter (WM), gray matter
      (GM), and cerebrospinal fluid (CSF), is challenging due to the low spatial
      resolution, severe partial volume effect, high image noise, and dynamic
      myelination and maturation processes. Atlas-based methods have been widely used
      for guiding neonatal brain segmentation. Existing brain atlases were generally
      constructed by equally averaging all the aligned template images from a
      population. However, such population-based atlases might not be representative of
      a testing subject in the regions with high inter-subject variability and thus
      often lead to a low capability in guiding segmentation in those regions.
      Recently, patch-based sparse representation techniques have been proposed to
      effectively select the most relevant elements from a large group of candidates,
      which can be used to generate a subject-specific representation with rich local
      anatomical details for guiding the segmentation. Accordingly, in this paper, we
      propose a novel patch-driven level set method for the segmentation of neonatal
      brain MR images by taking advantage of sparse representation techniques.
      Specifically, we first build a subject-specific atlas from a library of aligned,
      manually segmented images by using sparse representation in a patch-based
      fashion. Then, the spatial consistency in the probability maps from the subject
      specific atlas is further enforced by considering the similarities of a patch
      with its neighboring patches. Finally, the probability maps are integrated into a
      coupled level set framework for more accurate segmentation. The proposed method
      has been extensively evaluated on 20 training subjects using leave-one-out cross
      validation, and also on 132 additional testing subjects. Our method achieved a
      high accuracy of 0.919+/-0.008 for white matter and 0.901+/-0.005 for gray
      matter, respectively, measured by Dice ratio for the overlap between the
      automated and manual segmentations in the cortical region. 

PMID- 23968735
TI  - Disrupted modular organization of resting-state cortical functional connectivity
      in U.S. military personnel following concussive 'mild' blast-related traumatic
      brain injury.
AB  - Blast-related traumatic brain injury (TBI) has been one of the "signature
      injuries" of the wars in Iraq and Afghanistan. However, neuroimaging studies in
      concussive 'mild' blast-related TBI have been challenging due to the absence of
      abnormalities in computed tomography or conventional magnetic resonance imaging
      (MRI) and the heterogeneity of the blast-related injury mechanisms. The goal of
      this study was to address these challenges utilizing single-subject, module-based
      graph theoretic analysis of resting-state functional MRI (fMRI) data. We acquired
      20min of resting-state fMRI in 63 U.S. military personnel clinically diagnosed
      with concussive blast-related TBI and 21 U.S. military controls who had blast
      exposures but no diagnosis of TBI. All subjects underwent an initial scan within
      90days post-injury and 65 subjects underwent a follow-up scan 6 to 12months
      later. A second independent cohort of 40 U.S. military personnel with concussive
      blast-related TBI served as a validation dataset. The second independent cohort
      underwent an initial scan within 30days post-injury. 75% of the scans were of
      good quality, with exclusions primarily due to excessive subject motion. Network
      analysis of the subset of these subjects in the first cohort with good quality
      scans revealed spatially localized reductions in the participation coefficient, a
      measure of between-module connectivity, in the TBI patients relative to the
      controls at the time of the initial scan. These group differences were less
      prominent on the follow-up scans. The 15 brain areas with the most prominent
      reductions in the participation coefficient were next used as regions of interest
      (ROIs) for single-subject analyses. In the first TBI cohort, more subjects than
      would be expected by chance (27/47 versus 2/47 expected, p<0.0001) had 3 or more
      brain regions with abnormally low between-module connectivity relative to the
      controls on the initial scans. On the follow-up scans, more subjects than
      expected by chance (5/37, p=0.044) but fewer subjects than on the initial scans
      had 3 or more brain regions with abnormally low between-module connectivity.
      Analysis of the second TBI cohort validation dataset with no free parameters
      provided a partial replication; again more subjects than expected by chance
      (8/31, p=0.006) had 3 or more brain regions with abnormally low between-module
      connectivity on the initial scans, but the numbers were not significant (2/27,
      p=0.276) on the follow-up scans. A single-subject, multivariate analysis by
      probabilistic principal component analysis of the between-module connectivity in
      the 15 identified ROIs, showed that 31/47 subjects in the first TBI cohort were
      found to be abnormal relative to the controls on the initial scans. In the second
      TBI cohort, 9/31 patients were found to be abnormal in identical multivariate
      analysis with no free parameters. Again, there were not substantial differences
      on the follow-up scans. Taken together, these results indicate that single
      subject, module-based graph theoretic analysis of resting-state fMRI provides
      potentially useful information for concussive blast-related TBI if high quality
      scans can be obtained. The underlying biological mechanisms and consequences of
      disrupted between-module connectivity are unknown, thus further studies are
      required. 

PMID- 23968738
TI  - Development of a time-stepping sediment budget model for assessing land use
      impacts in large river basins.
AB  - The use of river basin modelling to guide mitigation of non-point source
      pollution of wetlands, estuaries and coastal waters has become widespread. To
      assess and simulate the impacts of alternate land use or climate scenarios on
      river washload requires modelling techniques that represent sediment sources and
      transport at the time scales of system response. Building on the mean-annual
      SedNet model, we propose a new D-SedNet model which constructs daily budgets of
      fine sediment sources, transport and deposition for each link in a river network.
      Erosion rates (hillslope, gully and streambank erosion) and fine sediment sinks
      (floodplains and reservoirs) are disaggregated from mean annual rates based on
      daily rainfall and runoff. The model is evaluated in the Burdekin basin in
      tropical Australia, where policy targets have been set for reducing sediment and
      nutrient loads to the Great Barrier Reef (GBR) lagoon from grazing and cropping
      land. D-SedNet predicted annual loads with similar performance to that of a
      sediment rating curve calibrated to monitored suspended sediment concentrations.
      Relative to a 22-year reference load time series at the basin outlet derived from
      a dynamic general additive model based on monitoring data, D-SedNet had a median
      absolute error of 68% compared with 112% for the rating curve. RMS error was
      slightly higher for D-SedNet than for the rating curve due to large relative
      errors on small loads in several drought years. This accuracy is similar to
      existing agricultural system models used in arable or humid environments.
      Predicted river loads were sensitive to ground vegetation cover. We conclude that
      the river network sediment budget model provides some capacity for predicting
      load time-series independent of monitoring data in ungauged basins, and for
      evaluating the impact of land management on river sediment load time-series,
      which is challenging across large regions in data-poor environments. 

PMID- 23968739
TI  - Soft drinks consumption is associated with behavior problems in 5-year-olds.
AB  - OBJECTIVE: To examine soda consumption and aggressive behaviors, attention
      problems, and withdrawal behavior among 5-year-old children. STUDY DESIGN: The
      Fragile Families and Child Wellbeing Study is a prospective birth cohort study
      that follows a sample of mother-child pairs from 20 large US cities. Mothers
      reported children's behaviors using the Child Behavior Checklist at age 5 years
      and were asked to report how many servings of soda the child drinks on a typical
      day. RESULTS: In the sample of 2929 children, 52% were boys, 51% were African
      American, 43% consumed at least one serving of soda per day, and 4% consumed 4 or
      more servings per day. In analyses adjusted for sociodemographic factors,
      consuming one (beta, 0.7; 95% CI, 0.1-1.4), 2 (beta, 1.8; 95% CI, 0.8-2.7), 3
      (beta, 2.0; 95% CI, 0.6-3.4), or 4 or more (beta, 4.7; 95% CI, 3.2-6.2) servings
      was associated with a higher aggressive behavior score compared with consuming no
      soda. Furthermore, those who consumed 4 or more (beta, 1.7; 95% CI, 1.0-2.4) soda
      servings had higher scores on the attention problems subscale. Higher withdrawn
      behavior scores were noted among those consuming 2 (beta, 1.0; 95% CI, 0.3-1.8)
      or 4 or more (beta, 2.0; 95% CI, 0.8-3.1) soda servings compared with those who
      consumed no soda. CONCLUSION: We note an association between soda consumption and
      negative behavior among very young children; future studies should explore
      potential mechanisms that could explain this association.

PMID- 23968740
TI  - Serum 7-alpha-hydroxy-4-cholesten-3-one as a marker for bile acid loss in
      children.
AB  - OBJECTIVE: To establish age-related reference values for 7-alpha-hydroxy-4
      cholesten-3-one (C4) in a pediatric population and to investigate bile acid
      malabsorption in children with short bowel syndrome (SBS). STUDY DESIGN: Serum
      was obtained between 8:00 a.m. and 11:00 a.m. from 100 healthy children (52%
      males, 9 months to 18 years of age) after 10 hours of fasting. Pediatric patients
      with SBS served as disease controls (n = 12). Following solid-phase extraction
      and purification, C4 was determined by high-performance liquid chromatography
      using a ultraviolet detector at a wavelength of 241 nm. The upper limit of normal
      for C4 concentrations was defined as the mean plus 2 SD of the log-normal
      distribution. RESULTS: The mean concentration and SD of C4 in healthy children
      was 22.8 +/- 15.8 ng/mL with no relation to age or sex and an upper limit of
      normal of 66.5 ng/mL. Normal C4 values were found in 97 of 100 healthy children,
      and all 12 patients with SBS had C4 concentrations above 100 ng/mL (mean 299.6 +/
      167.8 ng/mL; range 105.7-562.1 ng/mL, P < .0001 compared with controls).
      CONCLUSIONS: The determined upper limit of normal for C4 concentration in healthy
      children corresponds to previously published levels in healthy adults and is
      independent of age and sex. The consistently elevated C4 concentrations in our
      patients with SBS confirm the reliability of this noninvasive, nonisotopic method
      to assess bile acid malabsorption in children.

PMID- 23968741
TI  - Impact of pubertal development on endothelial function and arterial elasticity.
AB  - OBJECTIVES: Little is known about the relation of pubertal development on
      endothelial function and arterial elasticity in children and adolescents;
      therefore, we compared brachial artery flow-mediated dilation and carotid artery
      elasticity across Tanner (pubertal) stages in children and adolescents. STUDY
      DESIGN: Blood pressure, fasting lipids, glucose and insulin, body fat, insulin
      sensitivity adjusted for lean body mass, brachial flow-mediated dilation (percent
      dilation and area under the curve), endothelium-independent dilation (peak
      dilation and area under the curve), and carotid artery elasticity were evaluated
      across pubertal stages (Tanner I vs Tanner II-IV vs Tanner V) in 344 children and
      adolescents (184 males, 160 females; ages 6 to 21 years). RESULTS: One hundred
      twenty-four subjects (mean age 8.23 +/- 0.15 years; 52 females) were Tanner stage
      I; 105 subjects (mean age 13.19 +/- 0.17 years; 47 females) were Tanner stages II
      IV; and 115 subjects (mean age 17.19 +/- 0.16 years; 61 females) were Tanner
      stage V. There were no significant differences for any of the measures of
      vascular structure and function across pubertal stages. CONCLUSION: Results of
      the current study indicate that smooth-muscle and endothelial function, as well
      as carotid artery elasticity, do not differ throughout pubertal development and
      that accounting for pubertal stage when reporting vascular data in children and
      adolescents may be unnecessary.

PMID- 23968742
TI  - Parent support improves weight loss in adolescents and young adults with Down
      syndrome.
AB  - OBJECTIVE: To assess whether parent training in behavioral intervention, combined
      with a 16-session nutrition and activity education program, would improve weight
      loss relative to nutrition and activity education alone in adolescents and young
      adults with Down syndrome. STUDY DESIGN: Twenty-one patients with Down syndrome
      aged 13-26 years with a body mass index >= 85 th percentile were enrolled and
      randomized to a 6-month nutrition and activity education intervention (n = 10) or
      to a nutrition and activity education+behaviorial intervention (n = 11), and
      followed for 6 months after the active intervention period (1-year follow-up).
      The primary outcome measure was body weight; secondary outcomes included
      percentage body fat by bioelectric impedance; intake of fruits, vegetables, and
      energy-dense low-nutrient snack food (treats) by 3-day food record; and
      moderate/vigorous physical activity by accelerometry. RESULTS: At 6 months, mean
      body weight in the nutrition and activity education+behavioral intervention group
      was 3.2 kg lower than that in the nutrition and activity education group (95% CI,
      1.0-5.5 kg; P = .005). Mean group differences were sustained at 1 year (3.6 kg;
      95% CI, 1.4-5.9 kg; P = .002). At 6 months, moderate/vigorous physical activity
      time increased by an average of 18 minutes/day compared with baseline in the
      nutrition and activity education+behavioral intervention group (P = .01) and
      decreased by 7 minutes/day in the nutrition and activity education group (P =
      .30). These changes were largely maintained at 1 year, but were not statistically
      significant. Vegetable intake in the nutrition and activity education+behavioral
      intervention group exceeded that in the nutrition and activity education group by
      a mean of 1.6 servings at 1 year (P = .009), but not at 6 months. No between
      group differences were observed for percentage body fat or consumption of fruits
      or treats. CONCLUSION: Parent-supported behavioral intervention appears to be a
      successful adjunct to a 6-month nutrition education intervention in achieving
      weight loss in adolescents and young adults with Down syndrome.

PMID- 23968743
TI  - Monoamine oxidase A and sudden infant death syndrome.

PMID- 23968744
TI  - Randomized trial of exclusive human milk versus preterm formula diets in
      extremely premature infants.
AB  - OBJECTIVE: To compare the duration of parenteral nutrition, growth, and morbidity
      in extremely premature infants fed exclusive diets of either bovine milk-based
      preterm formula (BOV) or donor human milk and human milk-based human milk
      fortifier (HUM), in a randomized trial of formula vs human milk. STUDY DESIGN:
      Multicenter randomized controlled trial. The authors studied extremely preterm
      infants whose mothers did not provide their milk. Infants were fed either BOV or
      an exclusive human milk diet of pasteurized donor human milk and HUM. The major
      outcome was duration of parenteral nutrition. Secondary outcomes were growth,
      respiratory support, and necrotizing enterocolitis (NEC). RESULTS: Birth weight
      (983 vs 996 g) and gestational age (27.5 vs 27.7 wk), in BOV and HUM,
      respectively, were similar. There was a significant difference in median
      parenteral nutrition days: 36 vs 27, in BOV vs HUM, respectively (P = .04). The
      incidence of NEC in BOV was 21% (5 cases) vs 3% in HUM (1 case), P = .08;
      surgical NEC was significantly higher in BOV (4 cases) than HUM (0 cases), P =
      .04. CONCLUSIONS: In extremely preterm infants given exclusive diets of preterm
      formula vs human milk, there was a significantly greater duration of parenteral
      nutrition and higher rate of surgical NEC in infants receiving preterm formula.
      This trial supports the use of an exclusive human milk diet to nourish extremely
      preterm infants in the neonatal intensive care unit.

PMID- 23968745
TI  - Associations of preterm births with child health and development: Japanese
      population-based study.
AB  - OBJECTIVE: To examine associations between the duration of gestation and health
      and development outcomes at 2.5 years and 5.5 years using a Japanese population
      based longitudinal survey (n = 47 015). STUDY DESIGN: Hospitalization was used as
      an indicator of physical health, and responses to questions about age-appropriate
      behaviors were used as an indicator of behavioral development. We conducted
      logistic regression analyses controlling for a set of neonatal and family
      factors. We also estimated population-attributable fractions. RESULTS: We
      observed a steady increase toward shorter duration of gestation in the risk of
      hospitalizations at age 2.5 years and 5.5 years and developmental delays at 2.5
      years (Plinear trend < .001 for all outcomes). We found associations only between
      extremely preterm birth and delayed behavioral development at age 5.5 years.
      CONCLUSION: There is a linear relationship between shorter duration of gestation
      and increased risk of later health and developmental problems. In line with
      Rose's "population paradox," the population-attributable risks for these problems
      are greater for moderately preterm infants compared with extremely preterm
      infants.

PMID- 23968746
TI  - Pediatric global health education: correlation of website information and
      curriculum.
AB  - OBJECTIVE: Web sites describing residency programs are initial sources of
      information for applicants. The correlation of global health content on pediatric
      residency program Web sites with reported curricula is unknown. To determine the
      accuracy of global health education, information on program Web sites was
      compared with queried program content responses. STUDY DESIGN: The Fellowship and
      Residency Electronic Interactive Database was used to assess pediatric residency
      programs' Web sites for global health education, applying American Academy of
      Pediatrics consensus guidelines. The authors developed a questionnaire using
      these consensus guidelines and contacted each program to assess Web site
      findings, and chi(2) tests were used to compare data from these 2 sources.
      RESULTS: Of 194 programs, 177 had operational Web sites, of which 98 participated
      in the questionnaire (55%). Ninety-three of 177 programs (53%) reported global
      health education on Web sites, whereas 80 of 98 programs (82%) reported global
      health education through direct questioning (P < .001). Results include provision
      of resident salaries during global health elective (Web site 5% vs questionnaire
      98%, P < .001), mandatory training before global health elective (8% vs 20%, P =
      .02), presence of global health elective curriculum (24% vs 75%, P < .001),
      postexperience debriefing (16% vs 29%, P = .05), and bidirectional resident
      exchange (2% vs 13%, P = .01). CONCLUSIONS: Results indicate continued expansion
      of pediatric global health education, but significant differences exist between
      information on Web sites and data obtained through direct questioning. Accurate
      representation of global health opportunities would allow for more informed
      decision-making among prospective applicants. Findings also suggest substantial
      variability in global health curricula that needs to be addressed through
      improved planning and cooperation among training programs.

PMID- 23968747
TI  - Prominent forehead hematomas ("goose-eggs") as an initial manifestation of
      hemophilia.
AB  - Prominent forehead hematomas, "goose-eggs," may suggest an underlying disorder of
      coagulation. We reviewed records of 324 children with hemophilia and confirmed
      that a goose-egg was the presenting feature leading to a diagnosis of hemophilia
      in 14 of them. Primary care providers should be aware of this unique presentation
      of hemophilia. 

PMID- 23968748
TI  - Read my lips: oral manifestations of systemic diseases.

PMID- 23968749
TI  - Diagnostic testing and treatment of pediatric headache in the emergency
      department.
AB  - OBJECTIVE: To describe the variability in diagnostic testing and treatment of
      headaches in children presenting to the emergency department (ED) with use of a
      nationally representative sample. STUDY DESIGN: This was a retrospective cohort
      study using the National Hospital Ambulatory Medical Care Survey during 2005
      2009. To assess the use of evidence-based treatment, we analyzed all patients <18
      years old in 2 groups: (1) primary discharge diagnosis of headache and (2)
      discharge diagnosis of migraine. RESULTS: Four hundred forty-eight sampled ED
      visits from 2005-2009 represented a national estimate of 1.7 million visits with
      a discharge diagnosis of headache. A total of 95 visits represented a national
      estimate of 340 000 visits with a discharge diagnosis of migraine. Median age was
      13.1 years and 60% were female with a primary diagnosis of headache. In this
      group, neuroimaging was performed in 37% of patients and 39% underwent blood
      tests. Nonsteroidal anti-inflammatory drugs and opioids were most commonly used
      for treatment. For children with a discharge diagnosis of migraine, approximately
      40% of patients received non-evidence-based treatment, most commonly with opioid
      medications, and >20% of patients underwent computed tomography scanning.
      CONCLUSIONS: There is significant variability in the evaluation and treatment of
      pediatric headache in the ED. Despite evidence-based clinical guidelines for
      migraine headache, a large number of children continue to receive opioids and
      ionizing radiation in the ED.

PMID- 23968750
TI  - Developmental delay in moderately preterm-born children with low socioeconomic
      status: risks multiply.
AB  - OBJECTIVE: To assess separate and joint effects of low socioeconomic status (SES)
      and moderate prematurity on preschool developmental delay. STUDY DESIGN:
      Prospective cohort study with a community-based sample of preterm- and term-born
      children (Longitudinal Preterm Outcome Project). We assessed SES on the basis of
      education, occupation, and family income. The Ages and Stages Questionnaire was
      used to assess developmental delay at age 4 years. We determined scores for
      overall development, and domains fine motor, gross motor, communication, problem
      solving, and personal-social of 926 moderately preterm-born (MP) (32-36 weeks
      gestation) and 544 term-born children. In multivariable logistic regression
      analyses, we used standardized values for SES and gestational age (GA). RESULTS:
      Prevalence rates for overall developmental delay were 12.5%, 7.8%, and 5.6% in MP
      children with low, intermediate, and high SES, respectively, and 7.2%, 4.0%, and
      2.8% in term-born children, respectively. The risk for overall developmental
      delay increased more with decreasing SES than with decreasing GA, but the
      difference was not statistically significant: OR (95% CI) for a 1 standard
      deviation decrease were: 1.62 (1.30-2.03) and 1.34 (1.05-1.69), respectively,
      after adjustment for sex, number of siblings, and maternal age. No interaction
      was found except for communication, showing that effects of SES and GA are mostly
      multiplicative. CONCLUSIONS: Low SES and moderate prematurity are separate risk
      factors with multiplicative effects on developmental delay. The double jeopardy
      of MP children with low SES needs special attention in pediatric care.

PMID- 23968751
TI  - Decline of medical student idealism in the first and second year of medical
      school: a survey of pre-clinical medical students at one institution.
AB  - BACKGROUND: Idealism declines in medical students over the course of training,
      with some studies identifying the beginning of the decline in year 3 of US
      curricula. PURPOSES: This study tested the hypothesis that a decline in medical
      student idealism is detectable in the first two years of medical school. METHODS:
      We sought to identify differences in survey responses between first-year (MS1)
      and second-year (MS2) medical students at the beginning (T1) and end (T2) of
      academic year 2010 on three proxies for idealism, including items asking about:
      (a) motivations for pursuing a medical career; (b) specialty choice; and (c)
      attitudes toward primary care. Principle component analysis was used to extract
      linear composite variables (LCVs) from responses to each group of questions;
      linear regression was then used to test the effect of on each LCV, controlling
      for race, ethnicity, rural or urban origins, gender, and marital status. RESULTS:
      MS2s placed more emphasis on status/income concerns (beta=0.153, p<0.001), and
      much less emphasis on idealism as a motivator (beta=-0.081, p=0.054), in pursuing
      a medical career; more likely to consider lifestyle and family considerations
      (beta=0.098, p=0.023), and less likely to consider idealistic motivations (beta=
      0.066, p=NS); and were more likely to endorse both negative/antagonistic
      (beta=0.122, p=0.004) and negative/sympathetic (beta=0.126, p=0.004) attitudes
      toward primary care. CONCLUSIONS: The results are suggestive that idealism
      decline begins earlier than noted in other studies, implying a need for
      curricular interventions in the first two years of medical school.

PMID- 23968753
TI  - Assessment of occupational radiation exposure in underground artisanal gold mines
      in Tongo, Upper East Region of Ghana.
AB  - Assessments of radon and gamma radiation levels were carried out in underground
      artisanal gold mines in Tongo. This is one of the numerous artisanal gold mining
      communities in Ghana. Solid State Nuclear Track Detectors (SSNTDs) were used to
      estimate the mean (222)Rn concentration and dose rates during the Harmattan
      season (November 2010 to February 2011). The values for the (222)Rn concentration
      at each monitoring site ranged from 14 +/- 4 Bq m(-3) to 270 +/- 9 Bq m(-3), with
      a mean value of 98 Bq m(-3). These measurements are well below the lower action
      level of 500 Bq m(-3) recommended by ICRP for workplaces. The activity
      concentrations of (40)K, (232)Th and (238)U were determined using gamma-ray
      spectroscopy method. The effective dose estimates of 0.11 +/- 0.02 mSv y(-1) to
      0.68 +/- 0.04 mSv y(-1) were below the allowable limit of 20 mSv per annum for
      occupational exposure control recommended by the ICRP. The total annual effective
      dose varied from 0.22 +/- 0.04 mSv y(-1) to 1.92 +/- 0.08 mSv y(-1).

PMID- 23968752
TI  - Early life arsenic exposure and acute and long-term responses to influenza A
      infection in mice.
AB  - BACKGROUND: Arsenic is a significant global environmental health problem.
      Exposure to arsenic in early life has been shown to increase the rate of
      respiratory infections during infancy, reduce childhood lung function, and
      increase the rates of bronchiectasis in early adulthood. OBJECTIVE: We aimed to
      determine if early life exposure to arsenic exacerbates the response to early
      life influenza infection in mice. METHODS: C57BL/6 mice were exposed to arsenic
      in utero and throughout postnatal life. At 1 week of age, a subgroup of mice were
      infected with influenza A. We then assessed the acute and long-term effects of
      arsenic exposure on viral clearance, inflammation, lung structure, and lung
      function. RESULTS: Early life arsenic exposure reduced the clearance of and
      exacerbated the inflammatory response to influenza A, and resulted in acute and
      long-term changes in lung mechanics and airway structure. CONCLUSIONS: Increased
      susceptibility to respiratory infections combined with exaggerated inflammatory
      responses throughout early life may contribute to the development of
      bronchiectasis in arsenic-exposed populations.

PMID- 23968754
TI  - Kocuria kristinae: a true pathogen in pediatric patients.
AB  - BACKGROUND: Kocuria kristinae is a Gram-positive microorganism, which has rarely
      been reported as a pathogen that causes infection in humans. Recently, a few
      studies had concluded that this pathogen can indeed cause infection in
      immunocompromised hosts. However, the number of reports on K. kristinae infection
      in pediatric patients is still relatively limited. METHODS: Clinical data on
      pediatric patients who had K. kristinae cells isolated from their blood specimens
      during the period from January 2008 to May 2012 in a tertiary-care hospital in
      northern Taiwan were gathered and analyzed. RESULTS: Among 12 patients with K.
      kristinae cells isolated from their blood specimens, laboratory test results
      confirmed seven to have K. kristinae bloodstream infection. Six of them were
      premature babies, and one had acute leukemia. The infections were all healthcare
      associated. All the six premature babies had clinical presentation of sepsis and
      were inserted with percutaneous central venous catheters. One patient had two
      sets of blood culture positive for K. kristinae infection, and two premature
      patients had two sets of K. kristinae isolated, one from blood culture and the
      other from catheter tip culture, both of which were done at the same time. The
      leukemic child was inserted with a Broviac catheter and had K. kristinae isolated
      from both blood specimen and Broviac catheter. In the remaining five patients, K.
      kristinae infection was considered to be contaminant because they had only one
      set of positive blood culture and had other recognized infections. CONCLUSION: K.
      kristinae can cause infections in premature babies and immunocompromised
      pediatric patients using long-term intravenous catheters. Therefore, K. kristinae
      should be considered as a true pathogen and proper treatment should be provided
      to all susceptible pediatric patients.

PMID- 23968755
TI  - Prognostic values of a combination of intervals between respiratory illness and
      onset of neurological symptoms and elevated serum IgM titers in Mycoplasma
      pneumoniae encephalopathy.
AB  - BACKGROUND/PURPOSE: To retrospectively analyze the clinical manifestations of
      Mycoplasma pneumoniae (M. pneumoniae)-associated encephalopathy in pediatric
      patients. METHODS: Pediatric patients with positive serum anti-M. pneumoniae
      immunoglobulin M (IgM) were enrolled in this study. Clinical signs and symptoms,
      laboratory data, neuroimaging findings, and electrophysiological data were
      reviewed. RESULTS: Of 1000 patients identified, 11 (1.1%; male:female ratio =
      7:4) had encephalopathy and were admitted to the pediatric intensive care unit.
      Clinical presentation included fever, symptoms of respiratory illness, and
      gastrointestinal upset. Neurological symptoms included altered consciousness,
      seizures, coma, focal neurological signs, and personality change. Neuroimaging
      and electroencephalographic findings were non-specific. Specimens of
      cerebrospinal fluid (CSF) for M. pneumoniae polymerase chain reaction (PCR) were
      negative. Higher M. pneumoniae IgM titers and longer intervals between
      respiratory and CNS manifestations were associated with worse outcomes.
      CONCLUSION: Clinical manifestations of M. pneumoniae-associated encephalopathy
      were variable. Diagnosis of M. pneumoniae encephalopathy should not rely on CSF
      detection of M. pneumoniae by PCR. M. pneumoniae IgM titers and intervals between
      respiratory and CNS manifestations might be possibly related to the prognosis of
      patients with M. pneumoniae-associated encephalopathy.

PMID- 23968756
TI  - Derivation of a clinical prediction rule for bloodstream infection mortality of
      patients visiting the emergency department based on predisposition, infection,
      response, and organ dysfunction concept.
AB  - BACKGROUND/PURPOSE: Bloodstream infection (BSI) is a serious infection with a
      high mortality. We aimed to construct a predictive scoring system to stratify the
      severity of patients with BSI visiting the emergency department (ED). METHODS: We
      conducted a retrospective cohort study consisting of patients who visited the ED
      of a tertiary hospital with documented BSI in 2010. The potential predictors of
      mortality were obtained via chart review. Multivariate logistic regression was
      utilized to identify predictors of mortality. Penalized maximum likelihood
      estimation (PMLE) was applied for score development. RESULTS: There were 1063
      patients with bacteremia included, with an overall 28-day mortality rate of 13.2%
      (n = 140). In multiple logistic regression with penalization, the independent
      predictors of death were "predisposition": malignancy (beta-coefficient, 0.65; +2
      points); "infection": Staphylococcus aureus (S. aureus) bacteremia (0.69; +2
      points), pneumonia (1.32; +4 points), and bacteremia with an unknown focus (0.70;
      +2 points); "response": body temperature <36  degrees C (1.17; +3 points), band
      form >5% (1.00; +3 points), and red blood cell distribution width (RDW) >15%
      (0.63; +2 points); and "organ dysfunction": pulse oximeter oxygen saturation <90%
      (0.72; +2 points) and creatinine >2 mg/dL (0.69; +2 points). The area under
      receiver operating characteristic curve (AUROC) for the model was 0.881 [95%
      confidence interval (CI), 0.848-0.913], with a better performance than the Pitt
      bacteremia score (AUROC: 0.750; 95% CI 0.699-0.800, p < 0.001). The patients were
      stratified into four risk groups: (1) low, 0-3 points, mortality rate: 1.5%; (2)
      moderate, 4-6 points, mortality rate: 10.5%; (3) high, 7-8 points, mortality
      rate: 28.6%; and (4) very high, >= 9 points, mortality rate: 65.5%. CONCLUSION:
      The new scoring system for bacteremia could facilitate the prediction of the risk
      of 28-day mortality for patients visiting the ED with BSI.

PMID- 23968757
TI  - Surgical technique influences HeartMate II left ventricular assist device
      thrombosis.
AB  - BACKGROUND: Thrombosis of the HeartMate II (HM2 [Thoratec Corporation,
      Pleasanton, CA]) is a potentially devastating complication. While attention has
      been focused on anticoagulation strategies to prevent this complication, the
      impact of surgical technique has not been assessed. METHODS: Patients undergoing
      HM2 implantation at two institutions were reviewed. Pump thrombosis (PT) was
      defined as a clinical syndrome that included more than 30% elevation in pump
      power, more than 30% elevation in lactate dehydrogenase, and greater than 20%
      decrease in hemoglobin with the presence of thrombus in the HM2 stator or rotor,
      or both, at explant or autopsy. A blinded clinician reviewed dimensions and
      angles of the HM2 obtained from chest x-ray films. Patients demonstrating PT were
      compared with patients having normal function. RESULTS: Of the 49 patients
      reviewed, 11 (22.4%) displayed evidence of PT at a median of 42 days after HM2
      implantation. Patient with PT had greater acute angulation of the HM2 inflow
      cannula immediately postoperatively (48.2 +/- 6.8 versus 65.4 +/- 9.2 degrees, p
      < 0.001) and after 30 days (50.1 +/- 8.0 versus 65.1 +/- 9.9 degrees, p < 0.001).
      Pump pocket depth was lower in the PT group immediately after HM2 implantation
      (107.0 +/- 41.9 versus 144.3 +/- 20.3 cm, p < 0.001) and after 30 days (86.0 +/-
      39.1 versus 113.1 +/- 25.4 cm, p = 0.02). Patients with evidence of PT did not
      have a decrease in end-diastolic diameter (76 +/- 9 versus 70 +/- 15 mm, p =
      0.24) whereas patients in the normal function group had effective remodeling of
      the left ventricle (70 +/- 10 versus 56 +/- 12 mm, p = 0.01). CONCLUSIONS:
      Meticulous surgical technique, which necessitates creating an adequately sized
      pump pocket and appropriately directing the inflow cannula at the time of
      operation, may reduce the risk of PT.

PMID- 23968758
TI  - Impact of preoperative chronic lung disease on survival after surgical aortic
      valve replacement.
AB  - BACKGROUND: An increasing number of patients requiring surgical aortic valve
      replacement (SAVR) present with chronic pulmonary obstructive disease (COPD). The
      purpose of this study was to compare patients who had a range of COPD from normal
      to severe and were undergoing SAVR. METHODS: Retrospective review of 2,379
      patients undergoing SAVR +/- coronary artery bypass grafting (CABG) from January
      2002 to April 2012 at a US academic institution was performed. COPD was defined
      according to the Society of Thoracic Surgeons (STS) adult cardiac database:
      normal (forced expiratory volume [FEV] > 75% predicted), mild (FEV in 1 second
      [FEV1] 60%-75%), moderate (FEV1 50%-59%), and severe (FEV1 < 50%). Multivariable
      logistic and Cox regression methods were used to determine independent
      association between COPD and short- and long-term outcomes. Selection bias
      adjustment was achieved using the STS predicted risk of mortality (PROM).
      Adjusted odds ratios (AORs) and adjusted hazard ratios (AHR) were calculated
      using the normal lung function group as the reference. Kaplan-Meier curves were
      created to estimate long-term survival. RESULTS: One thousand five hundred
      seventeen of 2,379 patients (63.8%) had isolated SAVR, whereas 862 of 2,379
      (36.2%) patients underwent SAVR + CABG. Preoperative COPD was common among
      patients (21.9%) undergoing SAVR +/- CABG and included 332 (14.0%) patients with
      mild COPD, 89 (3.7%) patients with moderate COPD, and 101 (4.2%) patients with
      severe COPD. Unadjusted in-hospital mortality rose significantly with COPD class,
      from 3.9% for those with no COPD to 9.6% to patients with severe COPD. After
      adjustment, in-hospital mortality was not statistically different in normal
      patients and in those with COPD. In contrast, when compared with normal patients,
      adjusted long-term survival was worse across levels of COPD: mild (AHR, 1.70; p <
      0.001), moderate (AHR, 2.25; p < 0.001), and severe (AHR, 2.28; p < 0.001).
      CONCLUSIONS: Preoperative COPD is common in the SAVR population and is associated
      with diminished long-term but not short-term survival.

PMID- 23968759
TI  - Functional status is highly predictive of outcomes after redo lung
      transplantation: an analysis of 390 cases in the modern era.
AB  - BACKGROUND: The aim of this study was to evaluate whether functional status is a
      predictor of outcomes after redo lung transplantation (LTx). METHODS: Adults
      undergoing redo LTx after implementation of the Lung Allocation Score (May 2005
      to December 2010) were identified in the United Network for Organ Sharing
      database. Patients were stratified into three groups based on functional status
      as measured before redo LTx by the Karnofsky scale: (1) no assistance required,
      (2) some assistance required, and (3) total assistance required. Outcomes after
      redo LTx were compared based on these preoperative functional cohorts. RESULTS: A
      total of 390 redo LTx were identified: 44 (11%) required no functional
      assistance, 176 (45%) required some assistance, and 170 (44%) required total
      assistance preoperatively. Overall survival at 1 year after redo LTx was
      significantly reduced in the total assistance group (56% versus 82% no
      assistance, versus 82% some assistance; p < 0.001). After risk adjustment,
      recipients requiring total assistance preoperatively were at significant risk for
      1-year mortality (odds ratio 3.72, p = 0.02). Overall, the preoperative
      functional assessment outperformed the Lung Allocation Score in predicting 1-year
      survival after redo LTx (c-index: 0.68 versus 0.58). Transplant survivors who
      required total assistance before redo LTx were also at increased risk of
      requiring total assistance after redo LTx (26% versus 0% no assistance, versus 3%
      some assistance; p < 0.001). CONCLUSIONS: These data suggest that performing redo
      LTx in patients requiring total functional assistance is associated with
      significant risk of early mortality and continued functional limitation, findings
      that may have important implications in organ allocation.

PMID- 23968760
TI  - Pathology and prognosis of persistent stable pure ground-glass opacity nodules
      after surgical resection.
AB  - BACKGROUND: This study aimed to show the pathologic results of pure ground glass
      opacities (pGGOs) that showed no change in patients who underwent surgical
      resection. METHODS: The data used in this study were collected from the records
      of patients who underwent surgical resection for pGGOs between January 2004 and
      December 2009. All pGGOs were detected and followed up until operation with high
      resolution computed tomography at our hospital and were followed up by computed
      tomography of the chest at least 2 years after operation. Surgical resection was
      performed for patients with pGGOs if no change was observed after a minimum of 1
      month of follow-up and if any growth of the nodules or newly formed solid
      components occurred in pGGOs of any size. RESULTS: Forty-six patients were
      enrolled into the study group. No changes in the pGGOs during serial follow-up
      occurred in 39 patients (84.8%), and 7 patients (15.2%) underwent surgical
      resection because of growth of the lesions or newly developed solid lesions
      during follow-up. Of 39 patients in the no-change group, pathologic types of the
      cancerous pGGOs in 23 patients included adenocarcinoma in situ in 21 patients,
      minimally invasive adenocarcinoma in 1 patient, and invasive adenocarcinoma in 1
      patient. In the change group, 5 patients were diagnosed with cancer. Between the
      two groups, there was no difference in sex, time intervals, or tumor size.
      Neither group had lymph node metastasis or recurrence. CONCLUSIONS: This study
      showed the pathology of persistent stable pGGO postoperatively, which confirmed
      the 59% chance of a cancer diagnosis including adenocarcinoma in situ, minimally
      invasive adenocarcinoma, or invasive adenocarcinoma.

PMID- 23968761
TI  - Coronary revascularization for patients with severe left ventricular dysfunction.
AB  - BACKGROUND: The efficacy of coronary artery bypass graft surgery (CABG) and
      percutaneous coronary intervention (PCI) in patients with coronary artery disease
      has been well defined by randomized controlled trials. However, patients with
      severe left ventricular dysfunction (ejection fraction <35%) were
      underrepresented in these trials, and management of these complex patients
      remains unclear. The purpose of this study was to compare the outcomes of
      patients with coronary artery disease and left ventricular dysfunction undergoing
      CABG versus PCI. METHODS: The Alberta Provincial Project for Outcome Assessment
      in Coronary Heart Disease (APPROACH), a clinical data collection and outcome
      monitoring initiative for the province of Alberta, Canada, was used to identify
      2925 patients with coronary artery disease and left ventricular dysfunction
      undergoing CABG (n = 1,326) or PCI (n = 1,599) between 1995 and 2008. Patients
      were propensity matched to obtain comparable subgroups among left ventricular
      dysfunction patients. RESULTS: Cox proportional hazard analysis of the propensity
      matched subgroups identified that CABG was significantly associated with lower
      rates of repeat revascularization and better survival compared with PCI at 1, 5,
      10, and 15 years. Other significant independent predictors of poor long-term
      survival included age, renal failure, heart failure, diabetes mellitus,
      peripheral vascular disease, prior myocardial infarction, left main coronary
      artery disease, and prior CABG. CONCLUSIONS: For patients with coronary artery
      disease and left ventricular dysfunction, CABG was associated with lower rates of
      repeat revascularization and improved survival over PCI, after adjustment for
      baseline risk profile differences. Further research exploring the factors leading
      to use of a particular revascularization modality in this patient population is
      required.

PMID- 23968762
TI  - Pleural recurrence and long-term survival after thoracotomy and thoracoscopic
      lobectomy.
AB  - BACKGROUND: There are concerns over procedure-related pleural dissemination
      during video-assisted thoracic surgery (VATS) lobectomy. We compared the
      incidence of pleural recurrence and long-term survival between patients
      undergoing thoracotomy and VATS lobectomy for non-small cell lung cancer (NSCLC)
      with visceral pleural invasion. METHODS: From 2004 to 2009, 2,774 patients
      underwent curative-intent pulmonary resection for NSCLC at our institution. Of
      those, 478 patients were pathologically confirmed to have visceral pleural
      invasion by primary tumor. Among these, 239 patients (50%) underwent VATS
      lobectomy and 239 (50%) underwent thoracotomy lobectomy. Their medical records
      were retrospectively reviewed and a propensity score-matched analysis was
      performed. RESULTS: Matching based on propensity scores produced 167 patients in
      each group. There were no significant differences between two groups in age, sex,
      histologic type, tumor size, and pathologic N stage. The median follow-up
      duration was 52 months. During follow-up, 14 patients (8.4%) from the VATS group
      and 12 (7.2%) from the thoracotomy group had ipsilateral pleural recurrence (p =
      0.735). There was no significant difference in the recurrence pattern between the
      two groups. Overall survival at 5 years was 83% and 74% in the VATS and
      thoracotomy groups, respectively (p = 0.16). Disease-free survival at 5 years was
      65% and 62% in the VATS and thoracotomy groups, respectively (p = 0.45).
      CONCLUSIONS: Compared with thoracotomy, VATS lobectomy does not seem to increase
      the risk of procedure-related pleural dissemination in patients with NSCLC with
      visceral pleural invasion. Long-term survival and pattern of recurrence were
      similar between the two groups.

PMID- 23968763
TI  - Preoperative beta-blocker use should not be a quality metric for coronary artery
      bypass grafting.
AB  - BACKGROUND: Preoperative beta-blockade for coronary artery bypass grafting (CABG)
      has become an accepted hospital quality metric. However, single-institution
      reports regarding the benefits of beta-blocker (beta-blocker) use are
      conflicting. The purpose of this study was to evaluate the associations between
      preoperative beta-blocker use and outcomes within a large, regional cohort.
      METHODS: Patient records from a statewide, multi-institutional Society of
      Thoracic Surgeons (STS) certified database for isolated CABG operations (2001 to
      2011) were extracted and stratified by preoperative beta-blocker use. The
      influence of preoperative beta-blockers on risk-adjusted outcomes was assessed by
      hierarchical regression modeling with adjustment for preoperative risk using
      calculated STS predictive risk indices. RESULTS: A total of 43,747 (age, 63
      years; beta-blocker 80% versus non beta-blocker 20%) patients were included.
      Median STS predicted risk of mortality scores for beta-blocker patients were
      incrementally lower (1.2% vs 1.4%, p < 0.001). Non beta-blocker patients more
      frequently developed pneumonia (3.5% vs 2.8%, p = 0.001), while beta-blocker
      patients surprisingly had greater intraoperative blood usage (16% vs 11%, p <
      0.001). There was no difference in unadjusted mortality (beta-blocker: 1.9% vs
      non beta-blocker: 2.2%, p = 0.15). After risk adjustment, preoperative beta
      blocker use was not associated with mortality (p = 0.63), morbidity, length of
      stay (p = 0.79), or hospital readmission (p = 0.97). CONCLUSIONS: Preoperative
      beta-blocker use is not associated with risk-adjusted mortality, several measures
      of morbidity, or hospital resource utilization after CABG operations. Thus, these
      data suggest that the routine use of preoperative beta-blockers for CABG
      operations should not be used as a measure of surgical quality.

PMID- 23968764
TI  - Transapical aortic valve replacement for severe aortic stenosis: results from the
      nonrandomized continued access cohort of the PARTNER trial.
AB  - BACKGROUND: Transapical (TA) aortic valve replacement was an integral part of the
      Placement of Transcatheter Aortic Valves (PARTNER) trial. Enrollment during the
      randomized trial included 104 transapical (premarket approval TA [PMA-TA]) and 92
      surgical aortic valve replacements (SAVR) within the TA cohort. On completion of
      the trial, enrollment continued in a nonrandomized continued access (NRCA)
      program. We compared the outcomes of NRCA-TA procedures with those of PMA-TA and
      SAVR. METHODS: In 22 centers, 975 patients underwent TA aortic valve replacement
      as part of the NRCA registry. Inclusion and exclusion criteria were unchanged
      from the previously reported PARTNER trial. All patients were followed up for at
      least 1 year. RESULTS: Thirty-day or in-hospital mortality was 8.8% for the NRCA
      TA cohort, compared with 10.6% and 12.0% for the PMA-TA and SAVR patients,
      respectively (p = 0.54). One-year mortality in the NRCA-TA cohort was 22.1%, not
      significantly lower than the mortality in PMA-TA and SAVR patients at 29.0% and
      25.3%, respectively (p = 0.27). Thirty-day or in-hospital stroke was 2.2% among
      NRCA-TA patients in contrast to the 6.7% stroke rate observed in the PMA-TA group
      and 5.4% in SAVR patients (p = 0.008). Lower rates of neurologic adverse events
      in the NRCA-TA group persisted at 1 year compared with the PMA-TA and SAVR
      patients. CONCLUSIONS: Among the 975 patients in the NRCA-TA cohort, rates of
      major outcomes including death and stroke compared favorably with outcomes of PMA
      TA and SAVR patients enrolled in the PARTNER trial. This trend toward improved
      outcomes may be attributed to improved patient selection, individual centers
      surmounting the procedural learning curve, and refinements in surgical technique.

PMID- 23968765
TI  - Minimally invasive resection for mediastinal ectopic parathyroid glands.
AB  - BACKGROUND: We reviewed our experience with ectopic mediastinal
      parathyroidectomy. METHODS: Between March 1980 and September 2010, mediastinal
      parathyroidectomy was performed in 33 patients with hypercalcemia secondary to
      hyperparathyroidism. RESULTS: Primary hyperparathyroidism was the main diagnosis
      in 32 patients (97%). Technetium-sestamibi scan was used in 23 (70%) for
      preoperative localization. Minimally invasive resections were performed in 18
      patients (55%), and 15 (45%) underwent open surgery. The most common minimally
      invasive surgery approach was video-assisted thoracoscopy in 9 patients (27%);
      the most common open approach was median sternotomy in 11 (33%). Intraoperative
      parathyroid hormone monitoring was used in 22 patients (67%). The ectopic glands
      were intrathymic in 15 patients (45%), in the aortopulmonary window in 7 (21%),
      and in other intrathoracic locations in the remaining 11 (33%). Parathyroid
      adenomas were identified in 21 patients (64%); parathyroid hyperplasia and
      carcinoma were identified in 9 (27%) and 3 (9%), respectively. No early mortality
      occurred in either group. Reoperation was required in 1 patient in the minimally
      invasive surgery group because of hemothorax. Morbidity occurred in 8 patients
      (24%), the most common of which was hypocalcemia in 4 (12%). The mean length of
      stay was significantly shorter in the minimally invasive surgery group (2 versus
      6 days; p < 0.001) but mortality and morbidity were not statistically different
      between the two groups (p = 0.05). Mean follow-up was 3 +/- 3.7 years.
      CONCLUSIONS: Minimally invasive mediastinal parathyroidectomy has similar
      outcomes to open surgery, with significantly shorter length of hospital stay.

PMID- 23968766
TI  - Pulmonary artery endothelial cell phenotypic alterations in a large animal model
      of pulmonary arteriovenous malformations after the Glenn shunt.
AB  - BACKGROUND: Longevity of the superior cavopulmonary connection (SCPC) is limited
      by the development of pulmonary arteriovenous malformations (PAVM). The goal of
      this study was to determine whether phenotypic changes in pulmonary artery
      endothelial cells (PAEC) that favor angiogenesis occur with PAVM formation.
      METHODS: A superior vena cava to right pulmonary artery connection was
      constructed in 5 pigs. Pulmonary arteries were harvested at 6 to 8 weeks after
      surgery to establish cultures of PAEC and smooth muscle cells, to determine cell
      proliferation, gene expression, and tubule formation. Abundance of proteins
      related to angiogenesis was measured in lung tissue. RESULTS: Contrast
      echocardiography revealed right-to-left shunting, consistent with PAVM formation.
      While the proliferation of smooth muscle cells from the right pulmonary artery
      (shunted side) and left pulmonary artery (nonshunted side) were similar, right
      PAEC proliferation was significantly higher. Expression profiles of genes
      encoding cellular signaling proteins were higher in PAECs from the right
      pulmonary artery versus left pulmonary artery. Protein abundance of angiopoietin
      1, and Tie-2 (angiopoietin receptor) were increased in the right lung (both p <
      0.05). Tubule formation was increased in endothelial cells from the right
      pulmonary artery compared with the left pulmonary artery (404 +/- 16 versus 199
      +/- 71 tubules/mm(2), respectively; p < 0.05). CONCLUSIONS: These findings
      demonstrate that PAVMs developed in a clinically relevant animal model of SCPC
      concomitantly with differential changes in PAEC proliferative ability and
      phenotype. Moreover, there was a significant increase in the angiopoietin/Tie-2
      complex in the right lung, which may provide novel therapeutic targets to
      attenuate PAVM formation after a SCPC.

PMID- 23968767
TI  - Current outcomes for tricuspid valve infective endocarditis surgery in North
      America.
AB  - BACKGROUND: Tricuspid valve (TV) infective endocarditis (IE) accounts for 15% of
      IE cases and usually is treated medically. Surgical intervention is rare, and
      understanding of treatment options is based on small series of patients. The
      purpose of this study was to describe the population and outcomes for isolated TV
      IE using The Society of Thoracic Surgeons Adult Cardiac Database. METHODS:
      Between 2002 and 2009, 910 operations for TV IE were performed. Procedures
      included replacement, repair, and valvectomy. Healed IE was present in 31.4% (n =
      286), and active IE, in 68.5% (n = 624). Baseline patient characteristics as well
      as operative mortality and morbidity were analyzed, and univariate statistical
      differences were evaluated by Kruskal-Wallis test and stratum-adjusted Mantel
      Haenszel chi(2) tests. RESULTS: The median age was 40 years, with 50.6% male.
      Replacement of the TV was the most common procedure (n = 490; 53.8%), followed by
      TV repair (n = 354; 38.9%) and valvectomy (n = 66; 7.2%). Overall operative
      mortality was 7.3%, with no significant difference in mortality among valvectomy
      12%, repair 7.6%, and replacement 6.3% (p = 0.34). Compared with the active
      group, healed patients experienced a trend toward lower operative mortality (4.2%
      versus 8.6%; p = 0.06), lower complication rates (35.6% versus 51.4%; p =
      0.0004), and shorter overall length of stay (12 versus 22 days; p < 0.0001).
      CONCLUSIONS: Isolated TV operation for IE is a rare clinical entity with a
      similar operative mortality to left-sided IE operations. Repair and replacement
      of the TV had similar perioperative mortality. Patients in the healed TV IE group
      demonstrated lower complication rates, length of stay, and a trend toward
      decreased mortality.

PMID- 23968768
TI  - The role of health economic analyses in vaccine decision making.
AB  - Beginning in the 20th century with the consideration of the seven-valent
      pneumococcal conjugate vaccine in the US, the cost effectiveness became a topic
      of discussion when this vaccine was being considered for universal use by the US
      Advisory Committee on Immunization practices (ACIP). In 2008, the ACIP began
      using formal criteria for the presentation of such data and their inclusion in
      ACIP discussions. More recently, the US Institute of Medicine has recommended
      that health economic considerations play a primary role in the prioritization of
      future vaccine for development. However, such analyses can be biased towards
      vaccines that provide economic benefit rather than those that reduce severe
      morbidity and mortality. This is because the economic impact of minor common
      events that result in medical utilization or time lost from work for parents can
      outweigh the economic impact of severe morbidity and mortality. Thus diseases
      with a low mortality and morbidity but with a common clinical manifestation such
      as the common cold could be prioritized over vaccines against diseases such as
      meningococcal sepsis where the morbidity and mortality associated with each case
      is very high, but there is no associated common clinical syndrome. Thus the use
      of cost effectiveness analyses as a 'gating criteria' to decide which vaccines
      should be developed or routinely used runs the risk of transforming vaccines into
      primarily a tool for achieving cost savings within the health care system rather
      than a public health intervention targeting human suffering, death and
      disability. It is the purpose of this article to review the framework under which
      health economic evaluations can be undertaken, to review the experience with and
      reliability of such analyses, and to discuss the potential negative implications
      of the use of health economic analyses as a primary decision making tool. 

PMID- 23968770
TI  - Symptomatic pericardial effusion after chemoradiation therapy in esophageal
      cancer patients.
AB  - PURPOSE: We investigated clinical and treatment-related factors as predictors of
      symptomatic pericardial effusion in esophageal cancer patients after concurrent
      chemoradiation therapy. METHODS AND MATERIALS: We reviewed 214 consecutive
      primary esophageal cancer patients treated with concurrent chemoradiation therapy
      between 2001 and 2010 in our institute. Pericardial effusion was detected on
      follow-up computed tomography. Symptomatic effusion was defined as effusion
      >=grade 3 according to Common Terminology Criteria for Adverse Events v4.0
      criteria. Percent volume irradiated with 5 to 65 Gy (V5-V65) and mean dose to the
      pericardium were evaluated employing dose-volume histograms. To evaluate
      dosimetry for patients treated with two-dimensional planning in the earlier
      period (2001-2005), computed tomography data at diagnosis were transferred to a
      treatment planning system to reconstruct three-dimensional plans without
      modification. Optimal dosimetric thresholds for symptomatic pericardial effusion
      were calculated by receiver operating characteristic curves. Associating clinical
      and treatment-related risk factors for symptomatic pericardial effusion were
      detected by univariate and multivariate analyses. RESULTS: The median follow-up
      was 29 (range, 6-121) months for eligible 167 patients. Symptomatic pericardial
      effusion was observed in 14 (8.4%) patients. Dosimetric analyses revealed average
      values of V30 to V45 for the pericardium and mean pericardial doses were
      significantly higher in patients with symptomatic pericardial effusion than in
      those with asymptomatic pericardial effusion (P<.05). Pericardial V5 to V55 and
      mean pericardial doses were significantly higher in patients with symptomatic
      pericardial effusion than in those without pericardial effusion (P<.001). Mean
      pericardial doses of 36.5 Gy and V45 of 58% were selected as optimal cutoff
      values for predicting symptomatic pericardial effusion. Multivariate analysis
      identified mean pericardial dose as the strongest risk factor for symptomatic
      pericardial effusion. CONCLUSIONS: Dose-volume thresholds for the pericardium
      facilitate predicting symptomatic pericardial effusion. Mean pericardial dose was
      selected based not only on the optimal dose-volume threshold but also on the most
      significant risk factor for symptomatic pericardial effusion.

PMID- 23968769
TI  - The live attenuated chimeric vaccine rWN/DEN4Delta30 is well-tolerated and
      immunogenic in healthy flavivirus-naive adult volunteers.
AB  - WNV has become the leading vector-borne cause of meningoencephalitis in the
      United States. Although the majority of WNV infections result in asymptomatic
      illness, approximately 20% of infections result in West Nile fever and 1% in West
      Nile neuroinvasive disease (WNND), which causes encephalitis, meningitis, or
      flaccid paralysis. The elderly are at particular risk for WNND, with more than
      half the cases occurring in persons older than sixty years of age. There is no
      licensed treatment for WNND, nor is there any licensed vaccine for humans for the
      prevention of WNV infection. The Laboratory of Infectious Diseases at the
      National Institutes of Health has developed a recombinant live attenuated WNV
      vaccine based on chimerization of the wild-type WNV NY99 genome with that of the
      live attenuated DENV-4 candidate vaccine rDEN4Delta30. The genes encoding the prM
      and envelope proteins of DENV-4 were replaced with those of WNV NY99 and the
      resultant virus was designated rWN/DEN4Delta30. The vaccine was evaluated in
      healthy flavivirus-naive adult volunteers age 18-50 years in two separate
      studies, both of which are reported here. The first study evaluated 103 or 104
      PFU of the vaccine given as a single dose; the second study evaluated 105 PFU of
      the vaccine given as two doses 6 months apart. The vaccine was well-tolerated and
      immunogenic at all three doses, inducing seroconversion to WNV NY99 in 74% (103
      PFU), 75% (104 PFU), and 55% (105 PFU) of subjects after a single dose. A second
      105 PFU dose of rWN/DEN4Delta30 given 6 months after the first dose increased the
      seroconversion rate 89%. Based on the encouraging results from these studies,
      further evaluation of the candidate vaccine in adults older than 50 years of age
      is planned.

PMID- 23968771
TI  - Motor stereotypy after cardiac surgery.

PMID- 23968772
TI  - Characterisation of a functional allatotropin receptor in the bumblebee, Bombus
      terrestris (Hymenoptera, Apidae).
AB  - Allatotropins (ATs) are multifunctional neuropeptides initially isolated from the
      tobacco hornworm, Manduca sexta, where they were found to stimulate juvenile
      hormone synthesis and release from the corpora allata. ATs have been found in a
      wide range of insects, but appear to be absent in Drosophila. The first AT
      receptor (ATR) was characterised in 2008 in the lepidopteran Bombyx mori. Since
      then ATRs have been characterised in Coleoptera and Diptera and in 2012, an AT
      precursor gene was identified in hymenopteran species. ATRs show large sequence
      and structural similarity to vertebrate orexin receptors (OXR). Also, AT in
      insects and orexin in vertebrates show some overlap in functions, including
      modulation of feeding behaviour and reproduction. The goal of this study was to
      identify a functional ATR in a hymenopteran species. We used ATRs (insect
      sequences) and OXRs (vertebrate sequences) to search the genome of the bumblebee,
      Bombus terrestris. Two receptors (XP_003402490 and XP_003394933) with resemblance
      to ATRs and OXRs were found. Phylogenetic analysis provided the first indication
      that XP_003402490 was more closely related to ATRs than XP_003394933. We
      investigated the transcript level distribution of both receptors and the AT
      precursor gene by means of quantitative real-time reverse transcriptase PCR.
      XP_003402490 displayed a tissue distribution comparable with ATRs in other
      species, with high transcript levels in the male accessory glands. After
      pharmacological characterisation, it appeared that XP_003402490 is indeed a
      functional ATR. Activation of the receptor causes an increase in intracellular
      calcium and cyclic AMP levels with an EC50 value in the low nanomolar to
      picomolar range. XP_003394933 remains an orphan receptor. 

PMID- 23968773
TI  - Analysis of protein expression in zebrafish during gonad differentiation by
      targeted proteomics.
AB  - The molecular mechanisms governing sex determination and differentiation in the
      zebrafish (Danio rerio) are not fully understood. To gain more insights into the
      function of specific genes in these complex processes, the expression of multiple
      candidates needs to be assessed, preferably on the protein level. Here, we
      developed a targeted proteomics method based on selected reaction monitoring
      (SRM) to study the candidate sex-related proteins in zebrafish which were
      selected based on a global proteomics analysis of adult gonads and
      representational difference analysis of male and female DNA, as well as on
      published information on zebrafish and other vertebrates. We employed the
      developed SRM protocols to acquire time-resolved protein expression profiles
      during the gonad differentiation period in vas::EGFP transgenic zebrafish.
      Evidence on protein expression was obtained for the first time for several
      candidate genes previously studied only on the mRNA level or suggested by
      bioinformatic predictions. Tuba1b (tubulin alpha 1b), initially included in the
      study as one of the potential housekeeping proteins, was found to be
      preferentially expressed in the adult testis with nearly absent expression in the
      ovary. The revealed changes in protein expression patterns associated with gonad
      differentiation suggest that several of the examined proteins, especially Ilf2
      and Ilf3 (interleukin enhancer-binding factors 2 and 3), Raldh3 (retinaldehyde
      dehydrogenase type 3), Zgc:195027 (low density lipoprotein-related receptor
      protein 3) and Sept5a (septin 5a), may play a specific role in the sexual
      differentiation in zebrafish. 

PMID- 23968774
TI  - Hospital care of children with a cleft in England.
AB  - OBJECTIVE: To analyse hospital admissions in the first 2 years of life among
      children with cleft lip and/or palate in England. DESIGN: Analysis of national
      administrative data of hospital admissions. SETTING: National Health Service
      hospitals. PATIENTS: Patients born alive between 1997 and 2008 who underwent
      surgical cleft repair. OUTCOME MEASURES: Number of admissions, including the
      birth episode, and days spent in hospital were examined. Children were analysed
      according to cleft type and whether or not they had additional congenital
      anomalies. RESULTS: 10 892 children were included. In their first 2 years,
      children without additional anomalies (n=8482) had on average 3.2 admissions and
      13.2 days in hospital, which varied from 2.6 admissions and 9.2 days with cleft
      lip to 4.7 admissions and 19.7 days with bilateral cleft lip and palate (BCLP).
      Children with additional anomalies (n=2410) had on average 6.7 admissions and
      51.4 days in hospital, which varied from 6.4 admissions and 48.5 days with cleft
      palate to 8.8 admissions and 67.5 days with BCLP. The mean number and duration of
      cleft-related admissions was similar in children without (1.6 admissions and 6.4
      days) and in those with additional anomalies (1.5 admissions and 8.5 days). 35.2%
      of children without additional anomalies had at least one emergency admission,
      whereas the corresponding figure was 67.3% with additional anomalies.
      CONCLUSIONS: The burden of hospital care in the first 2 years of life varied
      according to cleft type and presence of additional anomalies. However, cleft
      specific hospital care did not differ between children with and without
      additional anomalies.

PMID- 23968775
TI  - The cost-effectiveness of diagnostic management strategies for children with
      minor head injury.
AB  - AIM: To estimate the cost-effectiveness of diagnostic management strategies for
      children with minor head injury and identify an optimal strategy. METHODS: A
      probabilistic decision analysis model was developed to estimate the costs and
      quality-adjusted life years (QALYs) accrued by each of six potential management
      strategies for minor head injury, including a theoretical 'zero option' strategy
      of discharging all patients home without investigation. The model took a lifetime
      horizon and the perspective of the National Health Service. RESULTS: The optimal
      strategy was based on the Children's Head injury Algorithm for the prediction of
      Important Clinical Events (CHALICE) rule, although the costs and outcomes
      associated with each strategy were broadly similar. CONCLUSIONS: Liberal use of
      CT scanning based on a high sensitivity decision rule is not only effective but
      also cost saving, with the CHALICE rule being the optimal strategy, although
      there is some uncertainty in the results. Incremental changes in the costs and
      QALYs are very small when all selective CT strategies are compared. The estimated
      cost of caring for patients with brain injury worsened by delayed treatment is
      very high compared with the cost of CT scanning. This analysis suggests that all
      hospitals receiving children with minor head injury should have unrestricted
      access to CT scanning for use in conjunction with evidence-based guidelines.

PMID- 23968776
TI  - Children's health and development: approaches to early identification and
      intervention.
AB  - Many children arrive at school with problems of development and behaviour which
      affect their educational achievement and social interaction and can have lifelong
      consequences. There is a strong association between developmental vulnerability
      at school entry and a well-documented series of parent and family risk factors,
      often linked to social disadvantage. Strategies which are likely to make a
      difference to these children and improve outcomes include family support, high
      quality early education and care programmes in the preschool years, and early
      detection of emerging problems and risk factors. The evidence suggests that these
      services and programmes are best delivered within a framework of progressive
      universalism--a universal basket of services for all children and families, with
      additional support commensurate with additional needs. This provides the best
      opportunity for early identification and appropriate intervention for emerging
      developmental problems and family issues that impact on children's development.
      While there are a number of challenges that need to be addressed and overcome,
      such an approach is an important investment that will yield measurable
      educational, social and economic benefits over the long term.

PMID- 23968777
TI  - Empowering change: realist evaluation of a Scottish Government programme to
      support normal birth.
AB  - BACKGROUND: midwife-led care has consistently been found to be safe and effective
      in reducing routine childbirth interventions and improving women's experience of
      care. Despite consistent UK policy support for maximising the role of the midwife
      as the lead care provider for women with healthy pregnancies, implementation has
      been inconsistent and the persistent use of routine interventions in labour has
      given rise to concern. In response the Scottish Government initiated Keeping
      Childbirth Natural and Dynamic (KCND), a maternity care programme that aimed to
      support normal birth by implementing multiprofessional care pathways and making
      midwife-led care for healthy pregnant women the national norm. AIM: the
      evaluation was informed by realist evaluation. It aimed to explore and explain
      the ways in which the KCND programme worked or did not work in different
      maternity care contexts. METHODS: the evaluation was conducted in three phases.
      In phase one semi-structured interviews and focus groups were conducted with key
      informants to elicit the programme theory. At phase two, this theory was tested
      using a multiple case study approach. Semi-structured interviews and focus groups
      were conducted and a case record audit was undertaken. In the final phase the
      programme theory was refined through analyses and interpretation of the data.
      SETTING AND PARTICIPANTS: the setting for the evaluation was NHS Scotland. In
      phase one, 12 national programme stakeholders and 13 consultant midwives
      participated. In phase two case studies were undertaken in three health boards;
      overall 73 participants took part in interviews or focus groups. A case record
      audit was undertaken of all births in Scotland during one week in two consecutive
      years before and after pathway implementation. FINDINGS: government and health
      board level commitment to, and support of, the programme signalled its importance
      and facilitated change. Consultant midwives tailored change strategies, using
      different approaches in response to the culture of care and inter-professional
      relationships within contexts. In contexts where practice was already changing
      KCND was seen as validating and facilitating. In areas where a more medical
      culture existed there was strong resistance to change from midwives and medical
      staff and robust implementation strategies were required. Overall the pathways
      appeared to enable midwives to achieve change. KEY CONCLUSIONS: our study
      highlighted the importance of those involved in a change programme working across
      levels of hierarchy within an organisation and from the macro-context of national
      policy and institutions to the meso-context of regional health service delivery
      and the micro-context of practitioner's experiences of providing care. The
      assumptions and propositions that inform programmes of change, which are often
      left at a tacit level and unexamined by those charged with implementing them,
      were made explicit. This examination illuminated the roles of the three key
      change mechanisms adopted in the KCND programme - appointment of consultant
      midwives as programme champions, multidisciplinary care pathways, and midwife-led
      care. It revealed the role of the commitment mechanism, which built on the
      appointment of the local change champions. The analysis indicated that the
      process of change, despite these clear mechanisms, needed to be adapted to local
      contexts and responses to the implementation of KCND. IMPLICATIONS FOR PRACTICE:
      initial formative evaluation should be conducted prior to development of complex
      healthcare programmes to ensure that (1) the interventions will address the
      changes required, (2) key stakeholders who may support or resist change are
      identified, and (3) appropriate facilitation strategies are developed tailored to
      context.

PMID- 23968778
TI  - Why are young Canadians afraid of birth? A survey study of childbirth fear and
      birth preferences among Canadian University students.
AB  - OBJECTIVE: to examine attitudes towards birth that may be common among young
      adults who have been socialised into a medicalised birth culture. Specifically,
      we were interested in examining factors that might be associated with fear of
      birth and preferences for elective obstetric interventions among the next
      generation of maternity care consumers. DESIGN: secondary analysis of an online
      survey of university students. SETTING: British Columbia, Canada. PARTICIPANTS:
      students from the University of British Columbia (n=3680). A quarter of the
      sample comprised Asian students, which allowed for analysis of cultural
      differences in attitudes towards birth. Both male and female students
      participated in the study; results are reported for the full sample, and by
      gender. MEASUREMENTS: a six item fear of childbirth scale was developed, as well
      as a 4 item index that measures students' concerns over physical changes
      following pregnancy and birth and a 2 item scale that assesses students'
      attitudes towards obstetric technology. FINDINGS: as we hypothesised, students
      who were more fearful of birth preferred epidural anaesthesia and birth by CS.
      Worries over physical changes following pregnancy and birth, favourable attitudes
      towards obstetric technology, and exposure to pregnancy and birth information via
      the media were also significantly associated with a preference for CS. Fear of
      birth scores were highest among students who reported that the media had shaped
      their attitudes towards pregnancy and birth. Asian students had significantly
      higher fear of birth scores and were more likely to prefer CS, compared to
      Caucasian students. IMPLICATIONS FOR PRACTICE: young adults are contemplating
      pregnancy and birth in an increasingly technology-dependent society. Educational
      programmes aimed at reducing fear of childbirth and concerns over physical
      changes following pregnancy and childbirth might contribute to vaginal birth
      intentions among young adults. Midwives may use the findings to identify and
      counsel nulliparas who exhibit fear of birth and other childbirth attitudes that
      may predispose them to choose elective obstetric interventions.

PMID- 23968779
TI  - Mycobacterium chelonae abscesses associated with biomesotherapy, Australia, 2008.
AB  - An outbreak of skin abscesses occurred in Adelaide, Australia, in association
      with biomesotherapy, an alternative therapy practice. Mycobacterium chelonae was
      identified in 8 patient and 3 environmental samples. Our findings show M.
      chelonae infection can be associated with alternative therapies when infection
      control breaches occur. Tighter regulations of alternative therapy practices are
      needed.

PMID- 23968780
TI  - Different herd level factors associated with H1N1 or H1N2 influenza virus
      infections in fattening pigs.
AB  - Herd-level factors associated with European H1N1 or H1N2 swine influenza virus
      (SIV) infections were assessed by mean of a cross-sectional study carried out in
      125 herds in France. Serum samples from 15 fattening pigs in each herd were
      tested by haemagglutination inhibition. Data related to herd characteristics,
      biosecurity, management and housing conditions were collected by questionnaire
      during the farm visit. Climatic conditions in the post-weaning and fattening
      rooms, where the sampled pigs were housed, were measured over 20 h. Factors
      associated with H1N1 or H1N2 sero-positive status of the herd were identified by
      logistic regressions for binary outcome. For both subtypes, the odds for a herd
      to be SIV sero-positive increased if there were more than two pig herds in the
      vicinity (OR=3.2, 95% confidence interval (95% CI): 1.4-7.6, p<0.01 and OR=3.5,
      95% CI: 1.5-8.1 p<0.01 for H1N1 and H1N2 respectively). Different factors were
      specifically associated with either H1N1 or H1N2 SIV infections. The odds for a
      herd to be H1N1 sero-positive were significantly increased by having a large
      number of pigs per pen in the post-weaning room (OR=3.2, 95% CI: 1.2-8.6,
      p=0.02), temperature setpoints below 25  degrees C (OR=2.6, 95% CI: 1.1-6.4,
      p=0.03) and below 24  degrees C (OR=2.6, 95% CI: 1.1-6.1, p=0.03) for the heating
      device in the farrowing room and the ventilation controller, respectively, and
      moving the pigs to the fattening facility via a room housing older pigs (OR=3.3,
      95% CI: 1.1-9.6, p=0.03). A H1N2 sero-positive status was associated with a brief
      down period in the farrowing room (OR=2.6, 95% CI: 1.1-6.3, p=0.03), small floor
      area per pig in the post-weaning pen (OR=2.9, 95% CI: 1.2-7.0, p=0.02), large
      sized fattening room (OR=2.5, 95% CI: 1.1-5.9, p=0.03), lack of all-in all-out
      management in the fattening room (OR=2.4, 95% CI: 1.0-5.8, p=0.04) and a
      temperature range of less than 5  degrees C controlling ventilation in the
      fattening facilities (OR=3.2, 95% CI: 1.4-7.4, p<0.01). Factors related to
      external and internal biosecurity and to the control of inside climatic
      conditions should be considered together when implementing programmes to better
      control SIV infections.

PMID- 23968781
TI  - Lives forever changed: family bereavement experiences after sudden cardiac death.
AB  - AIM: To describe the bereavement experiences of families who survived the sudden
      cardiac death of a family member and identify meanings of loss. BACKGROUND:
      Approximately 325,000 people experience sudden cardiac death (SCD) annually. It
      is important to examine family experiences after SCD because of the life altering
      impact of death on surviving family members. METHODS: A descriptive design, using
      the qualitative method of narrative analysis, was used to analyze family stories
      of bereavement. RESULTS: Five themes were identified across seven families:
      sudden cardiac death ... boom; saying goodbye; grief unleashes volatile emotional
      reactions; life goes on ... but never back to normal; and meanings in loss.
      CONCLUSIONS: This study adds to an understanding of family bereavement and
      findings suggest that providing information about the cause of death and allowing
      family members to tell their stories are potentially important interventions for
      clinicians who interact with bereaved families.

PMID- 23968782
TI  - Selective tissue distribution and long circulation endowed by paclitaxel loaded
      PEGylated poly(epsilon-caprolactone-co-L-lactide) micelles leading to improved
      anti-tumor effects and low systematic toxicity.
AB  - High tumor targeting and sustained drug concentration are key points for
      successful anti-tumor therapy, however, it is a challenging task. In this work, a
      novel micelle formulation of paclitaxel (PTX) has been prepared for the purpose
      of prolonging the blood circulation time as well as improving the accumulation of
      the drug within the tumor tissue. PEGylated P(CL-co-LLA) (poly(epsilon
      caprolactone-co-L-lactide)) micelles containing PTX were prepared by solid
      dispersion-sonication method with a higher drug-loading efficiency and
      encapsulation ratio (28.4% and 94.7%, respectively). Pharmacokinetic study
      revealed that the drug-loading micelles exhibited a higher AUC values and a
      prolonged residence time of drug in the blood circulation than those of PTX
      injection. As demonstrated by tissue distribution and anti-tumor study in S180
      tumor-bearing mice, the PEG-P(CL-co-LLA)/PTX micelles displayed modified tissue
      distribution of PTX and increased accumulation of PTX in tumor, therefore,
      resulted in anti-tumor effects enhancement and drug concentration in the normal
      tissues reduction. Furthermore, the preliminary safety tests were performed by
      measuring the body weight, histopathology, blood cell counts and clinical
      chemistry parameters, and the results showed no subacute toxicity to
      hematological system, major organs or tissues in mice. Taken together, our
      valuation shows that PEG-P(CL-co-LLA) micelles is a potential drug delivery
      system of PTX for the effective treatment of the tumor and systematic toxicity
      reduction, thus, the micellar formulation can provide a useful alternative dosage
      form for i.v. administration of PTX.

PMID- 23968783
TI  - Ex vivo absorption of promestriene from oil-in-water emulsion into infant
      foreskin.
AB  - Hypospadias is a birth defect in which the urinary tract opening is not at the
      tip of the penis. Hypospadias surgery is frequently complicated by healing
      deficiencies. Topical treatments with oestrogens were reported to improve
      healing. In the present study, ex vivo percutaneous absorption of promestriene, a
      synthetic oestrogen resulting of the double esterification of estradiol was
      conducted as a pre-requisite for further clinical trial in infants. Penetration
      of promestriene into infant foreskin treated with commercial oil in water
      emulsion (10 MUg mg(-1)) for 24 h was characterized showing controlled release
      properties enabling epidermal concentration more than six times higher than
      dermal concentration (4.13+/-2.46 mg g(-1) versus 0.62+/-0.84 mg g(-1),
      respectively). Furthermore, apparent promestriene fluxes into and through the
      skin (i.e., 1.5 MUg cm(-2) h(-1) and<0.89 MUg cm(-2) h(-1), respectively) were
      calculated from (i) drug amount retained into epidermis and dermis, or (ii) the
      limit of detection into the receptor fluid. In conclusion, less than 2% of
      initial dose were absorbed within 24h which compared well with others steroids
      applied topically in colloidal systems.

PMID- 23968784
TI  - Guidance of neural regeneration on the biomimetic nanostructured matrix.
AB  - Biomimetic materials are used for creating microsystems to control cell growth
      spatially and elicit specific cellular responses by combining complex
      biomolecules with nanostructured surfaces. Intercellular cell-to-cell and cell-to
      extracellular matrix (ECM) interactions in biomimetic materials have demonstrated
      potential in the development of drug discovery platforms and regeneration
      medicine. In this study, we developed a biomimetic nanostructured matrix by using
      various ECM molecular layers to create a biomimetic and biocompatible environment
      for realizing neuronal guidance in neural regeneration medicine. Silicon-based
      substrates possessing nanostructures were modified using different ECM proteins
      and peptides to develop a biomimetic and biocompatible environment for studying
      neural behaviors in adhesion, proliferation, and differentiation. The substrates
      were flat glass, flat silicon wafers (FWs), and nanorod-structured wafers
      prepared using wet etching. The three substrates were then functionalized using
      laminin-1 peptide, PA22-2-contained active isoleucine-lysine-valine-alanine
      valine (IKVAV) peptide, and poly-d-lysine (PDL), separately. When PC12 cells were
      cultured and differentiated on the modified substrates, the cells were able to
      elongate the neurites on the glass and FW, which was coated with three types of
      peptide. More differentiated neurons were observed on the nanorod-structured
      wafers coated with laminin than on those coated with IKVAV or PDL. For achieving
      directional guidance of neurite outgrowth, substrates exhibiting a grating
      pattern of nanorods were partially collapsed by the pulling force of water,
      leaving few nanorods, which support the net form of laminin on the surface.
      Furthermore, we fabricated the topological nanostructure-patterned wafer coated
      with laminin and successfully manipulated the extension and direction of neurites
      by using more than 80 MUm of a single soma. This approach demonstrates potential
      as a facile and efficient method for guiding the direction of single axons and
      for enhancing neurite outgrowth in studies on nerve regenerative medicine.

PMID- 23968786
TI  - Measuring function in chronic progressive disorders.

PMID- 23968787
TI  - Implications of the Affordable Care Act for occupational therapy practitioners
      providing services to Medicare recipients.
AB  - The passage of the Patient Protection and Affordable Care Act of 2010 (ACA; Pub.
      L. 111-148) represents the largest expansion in government funding of health care
      since Medicare and Medicaid were established in 1965 (Curfman, Abel, & Landers,
      2012). Although the health insurance mandate and Medicaid expansion have received
      the most attention as a result of legal challenges and the July 2012 Supreme
      Court ruling on the legality of the ACA (Henry J. Kaiser Family Foundation,
      2012), other ACA initiatives may have even greater implications for occupational
      therapy. The ACA includes sections on improving quality and health systems
      performance for Medicare recipients, with some sections also applying to Medicaid
      recipients. Insurance companies commonly follow Medicare rules; therefore, the
      Medicare reforms are likely to spread across all payers, health care settings,
      and care recipients. 

PMID- 23968788
TI  - Effectiveness of a 10-week tier-1 response to intervention program in improving
      fine motor and visual-motor skills in general education kindergarten students.
AB  - OBJECTIVE: This study examined the efficacy of a 10-wk Tier 1 Response to
      Intervention (RtI) program developed in collaboration with classroom teachers to
      improve the fine motor and visual-motor skills of general education kindergarten
      students. METHOD: We recruited 113 students in six elementary schools. Two
      general education kindergarten classrooms at each school participated in the
      study. Classrooms were randomly assigned to the intervention and control groups.
      Fine motor skills, pencil grip, and visual-motor integration were measured at the
      beginning of the school year and after the 10-wk intervention. RESULTS: The
      intervention group demonstrated a statistically significant increase in fine
      motor and visual-motor skills, whereas the control group demonstrated a slight
      decline in both areas. Neither group demonstrated a change in pencil grip.
      CONCLUSION: This study provides preliminary evidence that a Tier 1 RtI program
      can improve fine motor and visual-motor skills in kindergarten students.

PMID- 23968789
TI  - Performance-based measure of executive function: comparison of community and at
      risk youth.
AB  - OBJECTIVE: We compared abilities and strategy use of at-risk youth aged 16-21 yr
      with those of a community sample of high school students using a performance
      measure of executive function, the Weekly Calendar Planning Activity (WCPA).
      METHOD: We recruited students from an alternative school for at-risk youth (n =
      113) and from community high schools in the same region (n = 49). We collected
      demographic information from and administered the WCPA to both groups. RESULTS:
      The at-risk group made more errors, used fewer strategies, and broke more rules
      than the community group; however, the groups were similar in average time for
      planning and task completion. Moderate relationships were found between WCPA and
      academic performance in the at-risk group. CONCLUSION: Comparison of at-risk and
      community youth provides support for discriminant validity of the WCPA and
      indicates that the WCPA is useful in identifying adolescents who are at risk for
      occupational performance deficits.

PMID- 23968790
TI  - Computer adaptive test approach to the assessment of children and youth with
      brachial plexus birth palsy.
AB  - This study examined the psychometric properties of item pools relevant to upper
      extremity function and activity performance and evaluated simulated 5-, 10-, and
      15-item computer adaptive tests (CATs). In a multicenter, cross-sectional study
      of 200 children and youth with brachial plexus birth palsy (BPBP), parents
      responded to upper-extremity (n = 52) and activity (n = 34) items using a 5-point
      response scale. We used confirmatory and exploratory factor analysis, ordinal
      logistic regression, item maps, and standard errors to evaluate the psychometric
      properties of the item banks. Validity was evaluated using analysis of variance
      and Pearson correlation coefficients. Results show that the two item pools have
      acceptable model fit, scaled well for children and youth with BPBP, and had good
      validity, content range, and precision. Simulated CATs performed comparably to
      the full item banks, suggesting that a reduced number of items provide similar
      information to the entire set of items. 

PMID- 23968791
TI  - Functional handwriting performance in school-age children with fetal alcohol
      spectrum disorders.
AB  - Handwriting is a critical skill for school success. Children with fetal alcohol
      spectrum disorders (FASD) often present with fine motor and visual-motor
      impairments that can affect handwriting performance, yet handwriting skills have
      not been systematically investigated in this clinical group. This study aimed to
      comprehensively describe handwriting skills in 20 school-age children with FASD.
      Children were tested with the Process Assessment of the Learner, 2nd Edition (PAL
      II), and the Visuomotor Precision subtest of NEPSY, a developmental
      neuropsychological assessment. Participants performed below average on PAL-II
      measures of handwriting legibility and speed and on NEPSY visual-motor precision
      tasks. In contrast, PAL-II measures of sensorimotor skills were broadly within
      the average range. Results provide evidence of functional handwriting challenges
      for children with FASD and suggest diminished visual-motor skills and increased
      difficulty as task complexity increases. Future research is needed to further
      describe the prevalence and nature of handwriting challenges in this population. 

PMID- 23968792
TI  - Observed recovery sequence in neurobehavioral function after severe traumatic
      brain injury.
AB  - OBJECTIVE: The Western Neuro Sensory Stimulation Profile (WNSSP) presents a
      hierarchy of items suggestive of a sequence of recovery. The aim of this study
      was to understand the sequence of recovery of neurobehavioral function in
      patients with brain injury and determine whether this sequence was consistent
      with the WNSSP test item order. METHOD: We conducted a retrospective clinical
      chart audit of 37 adult inpatients (mean age = 29 yr; 31 men, 6 women) with a
      diagnosis of traumatic brain injury and a minimum of two medical record entries
      on the WNSSP. The sequence of recovery was statistically derived from the content
      and structure of the WNSSP. RESULTS: Our analysis did not support the current
      item ordering of the WNSSP as a function of the sequence of recovery from coma,
      with the exception of the Arousal/Attention subscale. CONCLUSION: WNSSP item
      performance suggested a sequence of recovery; clinicians may consider a revised
      item order that reflects this observed order.

PMID- 23968793
TI  - Minimal depression: how does it relate to upper-extremity impairment and function
      in stroke?
AB  - OBJECTIVE. We sought to determine the association between minimal depression,
      upper-extremity (UE) impairment, and UE motor function in a cohort of
      participants with subacute stroke. METHOD. We conducted a retrospective,
      secondary analysis of an interventional study. Correlational analyses were
      performed using the following outcome measures: the UE section of the Fugl-Meyer
      Assessment (FM), the functional ability section of the Arm Motor Ability Test
      (AMAT), and the Beck Depression Inventory (BDI-II). RESULTS. We found a negative
      correlation between BDI-II and both the FM (-.120, p = .196) and the AMAT (-.110,
      p = .275); however, this correlation was not statistically significant. Women
      exhibited higher depression scores (8.75 +/- 0.78) than men (6.29 +/- 0.46; p =
      .008). CONCLUSION. Low levels of depression are not associated with UE motor
      impairment and function in people with minimal to moderate UE disability levels.
      Poststroke depression occurs more frequently in women, warranting additional
      research on sex-specific differences. Given the proliferation of UE therapies
      targeting this group, this information is important for effective therapy
      planning and implementation. 

PMID- 23968794
TI  - Enhanced task-oriented training in a person with dementia with Lewy bodies.
AB  - Despite the inevitable loss of function seen in people with progressive
      dementias, interventions for reversing or minimizing functional loss are
      understudied. Research supports task-oriented training, but practical gaps in how
      to best evaluate clients for this training and how to implement it in clinical
      settings may be thwarting translation to occupational therapy practice. We
      structured an intervention model called STOMP (Skill-building through Task
      Oriented Motor Practice) using a unique blend of task-oriented training and motor
      learning principles. In this article, we describe through a case study the
      process and outcome of using STOMP to improve functional skills in a woman with
      moderate dementia with Lewy bodies. Our findings suggest that STOMP has the
      potential to serve as a structure for the evaluation and treatment of
      occupational performance deficits in people with dementia and that this model
      warrants further investigation. 

PMID- 23968795
TI  - Driving assessment tools used by driver rehabilitation specialists: survey of use
      and implications for practice.
AB  - OBJECTIVE. This article describes the use of assessment tools by North American
      driver rehabilitation specialists (DRSs). PARTICIPANTS. Participants were 227
      self-identified DRSs from the combined databases of two national associations.
      MEASURES. Information was solicited through a self-administered survey about the
      driving evaluation process, assessment tools, and process for making fitness-to
      drive recommendations. RESULTS. More than 80% of the DRSs reported testing visual
      acuity, range of motion, muscle strength, and fine motor coordination. The most
      consistently used cognitive-perceptual tests were the Trail Making Tests, Motor
      Free Visual Perception Test-Revised, and short cognitive screening tests. A
      client's behind-the-wheel performance was the main factor in making a fitness-to
      drive recommendation. Few specialists are using computer-based tests or
      interactive driving simulators. CONCLUSION. Although use of the Useful Field of
      View((r)) has increased, there continues to be no consistency in cognitive
      assessments or guidelines for behind-the-wheel assessment. Implications for
      practice are discussed. 

PMID- 23968796
TI  - Predicting older driver on-road performance by means of the useful field of view
      and trail making test part B.
AB  - The Useful Field of View((r)) (UFOV) and Trail Making Test Part B (Trails B) are
      measures of divided attention. We determined which measure was more accurate in
      predicting on-road outcomes among drivers (N = 198, mean age = 73.86, standard
      deviation = 6.05). Receiver operating characteristic curves for the UFOV (Risk
      Index [RI] and Subtests 1-3) and Trails B significantly predicted on-road
      outcomes. Contrasting Trails B with the UFOV RI and subtests, the only difference
      was found between the UFOV RI and Trails B, indicating the UFOV RI was the best
      predictor of on-road outcomes. Misclassifications of drivers totaled 28 for the
      UFOV RI, 62 for Trails B, and 58 for UFOV Subtest 2. The UFOV RI is a superior
      test in predicting on-road outcomes, but the Trails B has acceptable accuracy and
      is comparable to the other UFOV subtests. 

PMID- 23968797
TI  - DVD training for depression identification and treatment in older adults: a two
      group, randomized, wait-list control study.
AB  - OBJECTIVE. To test the effectiveness of an educational intervention aimed at
      improving mental health knowledge and skills in occupational therapists working
      with older rehabilitation patients. METHOD. The DVD-format educational
      intervention was evaluated using a two-group randomized wait-list control design.
      Occupational therapists (n = 75) completed a 32-item knowledge questionnaire at
      three time points. Patient charts were reviewed (n = 960) at 3 months before and
      3 and 6 months after DVD training to evaluate clinical practice change. RESULTS.
      A two-way analysis of variance showed knowledge scores increased significantly
      for both groups after DVD training. A significant Group * Time interaction and
      significant main effects for time and group were found. Chart review data also
      showed significant increases in desired clinical behaviors in both groups after
      training. The greatest single item of clinical practice change was use of a
      standardized depression screen. CONCLUSION. DVD-based training can significantly
      improve mental health practice. 

PMID- 23968798
TI  - Population-centered life skills groups: perceptions of satisfaction and
      engagement.
AB  - PURPOSE. We examined the satisfaction with and engagement in population-centered
      life skills groups of women in a residential facility for substance dependence.
      METHOD. This study was a retrospective, cross-sectional analysis of 561 surveys
      designed to elicit Likert scale client ratings. Descriptive statistics were used
      to examine client satisfaction. Differences in client engagement by content focus
      and activity process were also examined by analyzing the median scores of eight
      life skills development questions using the Kruskal-Wallis test of medians.
      RESULTS. Collectively, 96.8% of those who completed the surveys were satisfied
      with the living skills groups; 73.3% strongly agreed, and 23.4% agreed. No
      significant differences (p > .05) were found in the median scores of the
      engagement responses by either content focus or activity process. CONCLUSION.
      Population-centered life skills groups conceptualized within a holistic Person
      Environment-Occupation model appear to be satisfactory and engaging interventions
      for women in recovery. 

PMID- 23968799
TI  - Occupational therapy based on Ayres Sensory Integration in the treatment of
      retentive fecal incontinence in a 3-year-old boy.
AB  - OBJECTIVE. We present the case report of a 3-yr-old boy with retentive fecal
      incontinence and sensory overresponsivity. Sensory integration theory was used to
      address the overresponsivity affecting the child's ability to acquire age
      appropriate toileting habits. We describe the 7 mo of treatment and 3 mo of
      follow-up in occupational therapy. METHOD. We analyzed a retrospective chart
      review of daily defecation log outcome data and parent interview. RESULTS.
      Notable improvements in acquiring age-appropriate toileting habits were
      documented and measured using daily defecation logs. Improvements in sensory
      processing were documented using the Sensory Profile and corroborated
      improvements in the child's ability to participate in toileting routines and
      parent report of improved quality of life. CONCLUSION. Occupational therapy using
      Ayres Sensory Integration((r)) was a useful framework for addressing this child's
      toileting habits. This case explicates occupational therapy using data-driven
      intervention principles to address the relationship among sensory processing,
      behavior, and occupational performance. 

PMID- 23968800
TI  - Household task participation of children with and without physical disability.
AB  - We examined household task participation patterns of 46 children and youth with
      and without physical disability (PD) and explored the effects of age on roles of
      and expectations for these children in household task participation. Children
      with PD did not differ significantly from those without PD in the number of
      household tasks they performed; however, they did require more assistance than
      those without PD. In both groups, younger children performed significantly fewer
      household tasks and required significantly more help than older children. These
      findings further support the discriminant validity of the Children Helping Out:
      Responsibilities, Expectations, and Supports (Dunn, 2004) measure of household
      task participation and its use with adolescents. Assessing such participation
      would help caregivers and practitioners more successfully prepare children and
      youths with PD for independent living. Considering the roles and opportunities
      for social participation inherent in many household tasks will contribute to the
      usefulness of examining such participation. 

PMID- 23968801
TI  - Five years later: achieving professional effectiveness to move
      neurorehabilitation forward.
AB  - The AOTA Centennial Vision outlined in 2007 challenged the occupational therapy
      profession to become a "powerful, widely recognized, science-driven, and evidence
      based" profession that could adapt to changing societal and cultural needs and
      flourish well into the future. That challenge can be met by simply being
      effective at what we do; this will increase our value and validate our worth.
      Neurorehabilitation in occupational therapy can also thrive if we verify that the
      interventions we use and the strategies we implement are grounded in evidence.
      Professional effectiveness will emerge by (1) increasing the dissemination of
      research that supports the methods we use and informs others of the successful
      patient outcomes we achieve and (2) expanding development and validation of
      instruments that quantitatively and qualitatively measure functional outcomes.
      Occupational therapists can individually develop professional effectiveness by
      fostering greater academic-clinical alliances, objectifying evaluation and
      intervention methods, and preparing future practitioners appropriately for
      evidence-driven practice. 

PMID- 23968802
TI  - Reducing cognitive load while teaching complex instruction to occupational
      therapy students.
AB  - Cognitive load theory is a field of research used to improve the learning of
      complex cognitive tasks by matching instruction to the learner's cognitive
      architecture. We used an experimental posttest control-group design to test the
      effectiveness of instruction designed to reduce cognitive load (CL) and improve
      instructional effectiveness in teaching complex instruction to 24 first-year
      master's students under authentic classroom conditions. We modified historically
      taught instruction using an isolated-to-interacting-elements sequencing approach
      intended to reduce high CL levels. We compared control and modified instructional
      formats using written assessment scores, subjective ratings of CL, and task
      completion times. Analysis of variance revealed significant differences for
      postinstruction, posttest CL ratings, and delayed written posttest scores (p <
      .05). No significant differences were identified for posttest completion times.
      Findings suggest that this approach can be used to improve instructional
      efficiency in teaching human locomotion to occupational therapy students. 

PMID- 23968803
TI  - The new NO donor Terpy induces similar relaxation in mesenteric resistance
      arteries of renal hypertensive and normotensive rats.
AB  - The present work aimed to investigate the cellular mechanisms involved on the
      vasorelaxation induced by the new nitric oxide donor [Ru(terpy)(bdq)NO](3+)
      (Terpy) in isolated mesenteric resistance artery and to compare the vascular
      responses in isolated vessels from 2K and 2K-1C hypertensive rats. We have used
      this artery because it is important to the control of vascular resistance and
      consequently to the blood pressure control. The NO donor Terpy induced relaxation
      in a concentration-dependent way in mesenteric resistance arteries. There were no
      differences between renal hypertensive (2K-1C) and normotensive (2K) in Terpy
      induced relaxation neither in NO released. The relaxation induced by Terpy was
      inhibited by the soluble guanylyl-cyclase (sGC) inhibitor ODQ both in 2K and in
      2K-1C with similar amplitude. In agreement with these data, the protein
      expression of the subunits alpha1 and beta1 of the enzyme sGC was not different
      between 2K-1C and 2K mesenteric bed. The relaxation induced by Terpy was
      inhibited by the cGMP-dependent protein kinase (G kinase) inhibitor or by the non
      selective K(+) channel blocker tetraethylamonium (TEA), but with no difference
      between 2K-1C and 2K arteries. The relaxation induced by Terpy was also inhibited
      by the SERCA inhibitor thapsigargin in both groups. Taken together, these results
      show that the vascular relaxation induced by the NO donor [Ru(terpy)(bdq)NO](3+)
      involves the activation of NO/sGC/cGMP/GK pathway, activation of K(+) channels
      sensitive to TEA and SERCA in normotensive and renal hypertensive rat mesenteric
      resistance arteries. Surprisingly, Terpy-induced vasorelaxation is similar in
      mesenteric resistance arteries of renal hypertensive and normotensive rats. 

PMID- 23968804
TI  - Dynamics of hepatitis B virus resistance substitutions correlates with
      virological response in lamivudine-refractory patients with entecavir rescue
      monotherapy.
AB  - Entecavir (ETV) demonstrates potent antiviral effects against lamivudine (LMV)
      resistant hepatitis B virus (HBV). This study was designed to investigate the
      impact of LMV resistance mutations on the outcome of ETV rescue therapy in LMV
      refractory patients. Twenty-six chronic hepatitis B patients who received ETV
      monotherapy for LMV resistance were enrolled. Dynamics of HBV DNA levels were
      monitored before and during ETV rescue therapy. Mutations in the HBV reverse
      transcriptase were examined by sequencing. LMV-resistant mutations (rtL180M
      and/or rtM204VI) were detected in 9 patients before ETV treatment and not in
      another 5 patients before and after the treatment. ETV therapy resulted in a
      greater reduction in the HBV DNA load in the patients with out LMV-associated
      mutations before treatment than in those with. Six patients with 100% LMV
      resistant HBV variants at week 12 posttreatment had significantly (P<0.01)
      greater HBV DNA levels at the end of follow-up than the other patients studied. A
      comparable outcome was achieved between the patients with or without emergence of
      LMV-resistant mutations during the ETV treatment. In conclusion, patients without
      100% LMV-resistant HBV mutants at week 12 and those without LMV-resistant
      mutations before treatment show a better response to ETV rescue therapy than the
      corresponding others. Therefore, individual treatment optimization is of
      significance in improving the efficacy of antiviral therapy for patients with
      chronic HBV infection.

PMID- 23968805
TI  - Apropos "Viral load in patients infected with dengue is modulated by the presence
      of anti-dengue IgM antibodies".

PMID- 23968806
TI  - Output control of da Vinci surgical system's surgical graspers.
AB  - INTRODUCTION: The number of robot-assisted surgeries performed with the da Vinci
      surgical system has increased significantly over the past decade. The
      articulating movements of the robotic surgical grasper are controlled by grip
      controls at the master console. The user interface has been implicated as one
      contributing factor in surgical grasping errors. The goal of our study was to
      characterize and evaluate the user interface of the da Vinci surgical system in
      controlling surgical graspers. MATERIALS AND METHODS: An angular manipulator with
      force sensors was used to increment the grip control angle as grasper output
      angles were measured. Input force at the grip control was simultaneously measured
      throughout the range of motion. Pressure film was used to assess the maximum
      grasping force achievable with the endoscopic grasping tool. RESULTS: The da
      Vinci robot's grip control angular input has a nonproportional relationship with
      the grasper instrument output. The grip control mechanism presents an intrinsic
      resistant force to the surgeon's fingertips and provides no haptic feedback. The
      da Vinci Maryland graspers are capable of applying up to 5.1 MPa of local
      pressure. CONCLUSIONS: The angular and force input at the grip control of the da
      Vinci robot's surgical graspers is nonproportional to the grasper instrument's
      output. Understanding the true relationship of the grip control input to grasper
      instrument output may help surgeons understand how to better control the surgical
      graspers and promote fewer grasping errors.

PMID- 23968807
TI  - Repeatability of anorectal manometry in healthy volunteers and patients.
AB  - BACKGROUND: Anorectal manometry is used extensively in the assessment of patients
      with disorders of the pelvic floor. The present study investigated the
      repeatability of anorectal manometry in healthy volunteers and patients. PATIENTS
      AND METHODS: A total of 30 healthy volunteers (15 men and 15 women) and 10
      patients with fecal incontinence (4 men and 6 women) underwent perfusion
      manometry and volumetry. Intraindividual variability was evaluated using the
      intraindividual correlation coefficient (ICC). Interindividual variability was
      expressed as the standard deviation from the calculated mean values. RESULTS: We
      found a high intraindividual correlation for the squeezing pressure (ICC 0.75
      0.95), vector volume (ICC 0.88-0.97), and rectal perception (ICC 0.82-0.98). The
      anal resting pressure showed moderate repeatability (ICC 0.60-0.72). However,
      with regard to sphincter asymmetry, rectal compliance, and the rectoanal
      inhibitory reflex, a wide range of variability was found. In the female
      volunteers, the squeezing pressure and vector volume were lower than in those in
      the male volunteers. The anal pressure, vector volume, thresholds for urgency,
      and the maximum tolerable volume were lower in the incontinent patients than in
      the healthy volunteers. CONCLUSIONS: The squeezing pressure, vector volume, and
      rectal perception allow a reliable analysis of anal sphincter function. Sphincter
      asymmetry, rectal compliance, and the rectoanal inhibitory reflex were of limited
      diagnostic value.

PMID- 23968808
TI  - Effects of mycophenolate mofetil on cutaneous lupus erythematosus in (NZB * NZW)
      F1 mice.
AB  - BACKGROUND: Few studies have evaluated the effects and precise molecular
      mechanism of mycophenolate mofetil (MMF) in the treatment of human cutaneous
      lupus erythematosus (CLE). Our findings shed light on the therapeutic effects of
      MMF in a UVB-induced NZB * NZW (NZBW) F1 CLE mouse model. METHODS: Continuous MMF
      treatment (60 mg/kg/day) was administered up to Day 50 from the beginning of UVB
      induction (Day 0; 20 weeks old), as the pathologic features of CLE are present
      after 50 days. The therapeutic effects of MMF treatment in NZBW lupus mice were
      examined by comparing histopathological changes, lupus band test (deposition of
      immune complexes at the dermal-epidermal junction) and colocalization of
      autoantibodies with a dermal autoantigen Dsg3, and by evaluating the associations
      of local matrix metalloprotease activities. RESULTS: MMF improved survival in the
      NZBW lupus mice from 35.7% to 81.8%. The proteinuria, blood urea nitrogen, and
      interleukin 6 levels were significantly reduced after MMF treatment. The dermal
      lymphocytic infiltration, deposition of immune complexes at the dermal-epidermal
      junction, colocalized autoantibodies with Dsg3, and epidermal matrix
      metalloprotease activity were also attenuated in MMF-treated NZBW F1 mice.
      CONCLUSION: The results confirmed that MMF could substantially attenuate skin
      damage due to CLE in the NZBW F1 mouse model.

PMID- 23968809
TI  - Mapping of cingulate motor function by cortical stimulation.
AB  - An 8-year-old boy with intractable left mesiofrontal lobe epilepsy underwent
      placement of stereotactic intracerebral depth electrodes to better localise the
      epileptogenic zone. Co-registration of preoperative MRI and post-electrode
      implantation CAT allowed for anatomical localisation of electrode contacts.
      Electrical stimulation of electrodes over the dorsal and ventral banks of the
      cingulate cortex on the left produced right foot dorsiflexion and right wrist and
      elbow flexion, respectively, demonstrating detailed representation of cingulate
      motor function in humans, somatotopically distributed along the banks of the
      cingulate sulcus, as seen in the non-human primate. [Published with video
      sequences]. 

PMID- 23968810
TI  - Self-administration education and polypharmacy in mechanical circulatory support
      patients.

PMID- 23968811
TI  - Diagnosis of hemolysis and device thrombosis with lactate dehydrogenase during
      left ventricular assist device support.

PMID- 23968812
TI  - Morphologic changes in the aortic wall media after support with a continuous-flow
      left ventricular assist device.
AB  - BACKGROUND: Continuous-flow left ventricular assist devices (LVADs) provide
      durable, reliable, energy-efficient long-term support. However, the biologic
      effects of continuous flow are not completely known. Therefore, we examined
      aortic wall morphology in patients with heart failure before and after prolonged
      circulatory support with a continuous-flow LVAD. METHODS: After applying a
      partial aortic occlusion vascular clamp in the lower half of the ascending aorta,
      we removed samples of aortic wall tissue and then attached the outflow graft of
      the pump. Samples were obtained from 11 patients (9 men and 2 women, mean age 65
      +/- 7 years) with severe heart failure at the time of LVAD implantation. We
      obtained matched specimens at explantation after heart transplantation (n = 5) or
      autopsy (n = 6). These specimens were removed from the distal ascending aorta,
      remote from the aortic anastomotic site. Tissue sections were stained with
      hematoxylin and eosin, Movat's pentachrome and Masson's trichrome. Smooth muscle
      actin immunohistochemistry was performed on all sections. To evaluate the
      morphology of the aortic wall media, we quantitatively graded tissue sections for
      medial thickness, medial degenerative changes, smooth muscle cell (SMC)
      disorientation and depletion, elastic fiber fragmentation and depletion, medial
      fibrosis and atherosclerotic changes. RESULTS: The mean duration of support was
      140 +/- 136 days (range 87 to 580 days). The histologic evaluation and comparison
      of specimens obtained before and after LVAD support showed significantly
      increased foci of medial degeneration, SMC depletion, elastic fiber
      fragmentation, medial fibrosis and atherosclerotic changes after LVAD support.
      Mean medial thickness was not significantly different after LVAD support. We
      observed similar changes between samples obtained at transplantation and those
      obtained at autopsy. CONCLUSIONS: After continuous-flow LVAD support, the
      morphology of the aortic wall media was altered in all of our patients. The
      clinical relevance of these findings is unknown.

PMID- 23968813
TI  - Ancylostoma ceylanicum, a re-emerging but neglected parasitic zoonosis.
AB  - Although Ancylostoma ceylanicum is known to be an endemic and widely distributed
      hookworm of dogs and cats in Asia, its contribution to human morbidity as a
      potentially zoonotic hookworm remains largely unexplored. Since its discovery by
      Lane (1913) as a 'new parasite' of humans a century ago, the hookworm has been
      regarded as a 'rare' and 'abnormal' parasite and largely overlooked in surveys of
      human parasites. Recent molecular-based surveys in Asia, however, have
      demonstrated that A. ceylanicum is the second most common hookworm species
      infecting humans, comprising between 6% and 23% of total patent hookworm
      infections. In experimentally induced infections, A. ceylanicum mimics the
      clinical picture produced by the anthroponotic hookworms of 'ground itch' and
      moderate to severe abdominal pain in the acute phase. Natural infections with A.
      ceylanicum in humans have been reported in almost all geographical areas in which
      the hookworm is known to be endemic in dogs and cats, however for the majority of
      reports, no clinical data are available. Much like the anthroponotic hookworm
      species, patent A. ceylanicum adults can isolate within the jejunum to produce
      chronic infections that on occasion, may occur in high enough burdens to produce
      anaemia. In addition, the hookworm can act much like Ancylostoma caninum and be
      found lower in the gastrointestinal tract leading to abdominal distension and
      pain, diarrhoea and occult blood in the faeces accompanied by peripheral
      eosinophilia. Whether A. ceylanicum is capable of producing both classical
      hookworm disease and evoking morbidity through an uncontrolled allergic response
      in some individuals remains unascertained. Future investigations combining the
      use of molecular diagnostic tools with clinical and pathological data will shed
      further light on its role as a human pathogen. The control of this zoonosis
      necessitates an integrated and inter-sectorial "One Health" approach be adopted
      in communities where large numbers of dogs share a close relationship with
      humans. 

PMID- 23968814
TI  - Alcohol and the methylome: design and analysis considerations for research using
      human samples.
AB  - BACKGROUND: A growing number of studies in human samples have sought to determine
      whether chronic alcohol use and alcohol use disorders (AUDs) may be associated
      with epigenetic factors, such as DNA methylation. We review the extant literature
      in light of some of the challenges that currently affect the design and
      interpretation of epigenetic research in human samples. METHOD: A literature
      search was used to identify studies that have examined DNA methylation in
      relation to alcohol use or AUDs in human samples (through July 2013). A total of
      22 studies were identified. RESULTS: Associations with quantitative or diagnostic
      phenotypes of alcohol use or AUDs have been reported for several genes. However,
      all studies to date have relied on relatively small samples and cross-sectional
      study designs. Additionally, attempts to replicate results have been rare. More
      generally, research progress is hampered by several issues, including limitations
      of the technologies used to assess DNA methylation, tissue- and cell-specificity
      of methylation patterns, the difficulties of relating observed methylation
      differences at a given locus to a functional effect, and limited knowledge about
      the molecular mechanisms underlying the effects of alcohol on DNA methylation.
      CONCLUSIONS: Although we share the optimism that epigenetics may lead to new
      insights into the etiology and pathophysiology of AUDs, the methodological and
      scientific challenges associated with conducting methylomic research in human
      samples need to be carefully considered when designing and evaluating such
      studies.

PMID- 23968815
TI  - Effects of methamphetamine on the noradrenergic activity biomarker salivary alpha
      amylase.
AB  - BACKGROUND: Methamphetamine (METH) potently activates the sympathetic nervous
      system (SNS) by increasing central and peripheral norepinephrine (NE). Salivary
      alpha-amylase (sAA) is a biomarker of SNS activation that correlates with plasma
      NE levels. The purpose of this study was to determine the impact of METH on sAA
      activity and whether changes in sAA activity were correlated with subjective
      effects ratings. METHODS: Non-treatment seeking METH-dependent volunteers (N=8)
      participated in this within-subjects laboratory-based study. Volunteers received
      randomly administered intravenous METH (0mg, 30 mg) and sAA activity,
      cardiovascular measures and subjective ratings were assessed at baseline (-15
      min) and five post-METH time points (10, 20, 30, 45, and 60 min). RESULTS: METH
      (30 mg) increased sAA activity over time. sAA activity significantly correlated
      with diastolic blood pressure following 0mg METH and systolic blood pressure
      following 30 mg METH. Subjective ratings (ANY EFFECT, HIGH, GOOD, STIMULATED,
      LIKE, WLLING TO PAY) highly correlated with sAA over five post-METH time points
      (N=40; r's=0.543-0.684, p's<0.001). Age, body mass index and METH amount received
      on a mg/kg basis were significantly associated with sAA activity. Multiple linear
      regression analysis indicated sAA activity remained a significant predictor of
      subjective ratings following METH after controlling for these factors.
      CONCLUSIONS: The NE peripheral biomarker sAA activity is associated with METH's
      subjective effects.

PMID- 23968816
TI  - Human parainfluenza virus type 3 in wild nonhuman primates, Zambia.
AB  - Human parainfluenza virus type 3 (HPIV3) genome was detected in 4 baboons in
      Zambia. Antibody for HPIV3 was detected in 13 baboons and 6 vervet monkeys in 2
      distinct areas in Zambia. Our findings suggest that wild nonhuman primates are
      susceptible to HPIV3 infection.

PMID- 23968817
TI  - Joint loading asymmetries in knee replacement patients observed both pre- and six
      months post-operation.
AB  - BACKGROUND: Studies have highlighted asymmetries in knee joint moments in
      individuals with osteoarthritis and joint replacements. However, there is a need
      to investigate the forces at the knee joints to establish the extent of loading
      asymmetries. METHODS: Twenty healthy (mean age, 62; range, 55-79 years) and 34
      pre- to post-knee arthroplasty (mean age, 64; range, 39-79 years) participants
      performed gait and sit-stand activities in a motion capture laboratory. Knee
      joint forces and moments were predicted using inverse dynamics and used to
      calculate peak loading and impulse data which were normalized to body weight.
      Comparisons were made between affected and contralateral limbs, and changes from
      pre- to post-knee arthroplasty. FINDINGS: Pre-knee arthroplasty peak vertical
      knee forces were greater in the contralateral limb compared to the affected limb
      during both gait 3.5 vs. 3.2 * body weight and sit-stand 1.8 vs. 1.5 * body
      weight. During gait, peak knee adduction moment asymmetries significantly changed
      from pre- to post-knee arthroplasty (-0.3 to 0.8 * % body weight * m * height),
      although differences in vertical knee forces remained. There were no significant
      changes in loading during sit-stand from pre- to post-knee arthroplasty. The
      healthy participants showed no noteworthy asymmetries. INTERPRETATION: This study
      showed loading asymmetries in knee forces between affected and contralateral
      limbs both pre- and post-knee arthroplasty. Continued over reliance of the
      contralateral limb could lead to pathology.

PMID- 23968818
TI  - Focal cortical dysplasia type IIIc associates with multiple cerebral cavernomas.
AB  - The distinction of isolated malformations and combined lesions constitutes a
      major novelty in the 2011 consensus classification of the International League
      against Epilepsy (ILAE) for focal cortical dysplasias (FCD). Cortical lamination
      abnormalities together with vascular lesions are subsumed as FCD IIIc. Little is
      known regarding frequency and etiology of this entity. Here, we systematically
      evaluated biopsy specimens from 72 drug-refractory epilepsy patients with
      cerebral cavernous malformations (CCM) regarding presence of associated FCD. Due
      to a non-perpendicular orientation of the cortical structures or absence of
      sufficient cortical tissue adjacent to the vascular lesion 25 samples were not
      classifiable. In the remaining 47 cases FCD IIIc was rare (4.3%), but
      significantly increased in patients with multiple CCM (28.6%; p<0.05 vs. single
      CCM). Association of FCD IIIc with multiple CCM may argue against FCD IIIc as an
      acquired lesion. 

PMID- 23968819
TI  - Stereotactic radiofrequency amygdalohippocampectomy: two years of good
      neuropsychological outcomes.
AB  - PURPOSE: To provide two-year seizure and neuropsychological outcomes in patients
      treated by stereotactic radiofrequency amygdalohippocampectomy (SAHE), an
      alternative, minimally invasive method for the treatment of mesial temporal lobe
      epilepsy (MTLE). MATERIAL AND METHODS: Thirty-seven MTLE patients treated by SAHE
      (26 left-sided, 11 right-sided) were included. Patients underwent
      neuropsychological evaluation by the Wechsler Adult Intelligence Scale-Revised
      and the Wechsler Memory Scale-Revised preoperatively, 1 year and 2 years after
      SAHE. RESULTS: Two years after SAHE twenty-eight (75.5%) patients were assessed
      as Engel Class I and seven (18.9%) patients as Engel Class II. In two patients
      (5.4%) treatment failed, one of them was classified as Class III and one as Class
      IV. Irrespective of the laterality of the procedure, the group improved
      significantly in Global and Verbal Memory Quotients, Attention, Delayed Recall,
      Semantic Long-term memory subtest and Working Memory. Additionally, increases in
      Full-scale, Verbal and Visual Intelligence Quotients were detected on the group
      level. CONCLUSION: In the present study we report good seizure control and
      neuropsychological outcomes after SAHE in our patients. We hypothesize that good
      neuropsychological results were achieved by the incomplete destruction of target
      structures, sparing the lateral temporal neocortex, and also partially by
      practice effect. Treatment failures in seizure control may be attributed to
      larger epileptogenic zones.

PMID- 23968820
TI  - Family history and frontal lobe seizures predict long-term remission in newly
      diagnosed cryptogenic focal epilepsy.
AB  - PURPOSE: Cryptogenic focal epilepsy (CFE) is a heterogeneous clinical disorder
      including patients with severe refractory forms and patients with a fairly good
      prognosis. Predictors of prognosis in CFE are poorly understood. The aim of this
      retrospective study is to identify long-term (5-year) prognostic predictors in
      patients with newly diagnosed CFE. METHODS: Subjects with cryptogenic focal
      epilepsy (CFE) seen from April 1987 to September 2011 in two twin Epilepsy
      Centres located in Reggio Calabria and Catanzaro, Calabria, Southern Italy, were
      screened. Patients were excluded if they had psychogenic seizures, major
      psychiatric disorders presence of brain lesions except for non-specific white
      matter T2-hyperintensities, short follow-up (less than five years) or for having
      received the diagnosis of CFE elsewhere. One hundred and eighty-six patients,
      firstly diagnosed in our Centres, constituted the study sample. Survival curves
      were generated according to the Kaplan-Meier method and compared with the log
      rank test. The endpoint was the cumulative time-dependent chance of 5-year
      remission after treatment start. Independent predictors of remission were tested
      by multivariate analysis using Cox proportional hazards function models. The
      accuracy of the resulting model was tested with Receiver Operating
      Characteristics (ROC) curve analysis. KEY FINDINGS: The cumulative incidence of
      remission was 23%. At Kaplan-Meier analysis, the only factor predicting remission
      was family history of epilepsy or febrile seizures (FS; p=0.02). At Cox
      regression, family history and frontal lobe epilepsy showed to be independent
      predictors of outcome (p=0.02 and 0.03, respectively). The accuracy of these
      predictors was good (area under ROC curve 0.648, 95% CI 0.575-0.716).
      Interestingly, we also found a considerable (7 years) diagnostic delay that did
      not result in a worse prognosis. SIGNIFICANCE: About one quarter of subjects with
      newly diagnosed CFE attains 5-year seizure remission during follow-up. Family
      history of epilepsy or FS and frontal localization are independent prognostic
      predictors.

PMID- 23968821
TI  - Functional imaging of auditory scene analysis.
AB  - Our auditory system is constantly faced with the task of decomposing the complex
      mixture of sound arriving at the ears into perceptually independent streams
      constituting accurate representations of individual sound sources. This
      decomposition, termed auditory scene analysis, is critical for both survival and
      communication, and is thought to underlie both speech and music perception. The
      neural underpinnings of auditory scene analysis have been studied utilizing
      invasive experiments with animal models as well as non-invasive (MEG, EEG, and
      fMRI) and invasive (intracranial EEG) studies conducted with human listeners. The
      present article reviews human neurophysiological research investigating the
      neural basis of auditory scene analysis, with emphasis on two classical paradigms
      termed streaming and informational masking. Other paradigms - such as the
      continuity illusion, mistuned harmonics, and multi-speaker environments - are
      briefly addressed thereafter. We conclude by discussing the emerging evidence for
      the role of auditory cortex in remapping incoming acoustic signals into a
      perceptual representation of auditory streams, which are then available for
      selective attention and further conscious processing. This article is part of a
      Special Issue entitled Human Auditory Neuroimaging.

PMID- 23968822
TI  - Spiral ganglion neuron quantification in the guinea pig cochlea using Confocal
      Laser Scanning Microscopy compared to embedding methods.
AB  - Neuron counting in the cochlea is a crucial but time-consuming operation for
      which various methods have been developed. To improve simplicity and efficiency,
      we tested an imaging method of the cochlea, and based on Confocal Laser Scanning
      Microscopy (CLSM), we visualised Rosenthal's Canal and quantified the spiral
      ganglion neurons (SGN) within. Cochleae of 8 normal hearing guinea pigs and one
      implanted with a silicone filament were fixed in paraformaldehyde (PFA),
      decalcified, dehydrated and cleared in Spalteholz solution. Using the tissue's
      autofluorescence, CLSM was performed at 100 fold magnification generating z
      series stacks of about 20 slices of the modiolus. In 5 midmodiolar slices per
      cochlea the perimeters of the Rosenthal's Canal were surveyed, representative
      neuron diameters were measured and the neurons first counted manually and then
      software-assisted. For comparison, 8 normal hearing guinea pig cochleae were
      embedded in paraffin and examined similarly. The CLSM method has the advantage
      that the cochleae remain intact as an organ and keep their geometrical structure.
      Z-stack creation is nearly fully-automatic and frequently repeatable with various
      objectives and step sizes and without visible bleaching. The tissue shows minimal
      or no shrinking artefacts and damage typical of embedding and sectioning. As a
      result, the cells in the cleared cochleae reach an average diameter of 21 MUm and
      a density of about 18 cells/10,000 MUm(2) with no significant difference between
      the manual and the automatical counts. Subsequently we compared the CLSM data
      with those generated using the established method of paraffin slides, where the
      SGN reached a mean density of 9.5 cells/10,000 MUm(2) and a mean soma diameter of
      13.6 MUm. We were able to prove that the semi-automatic CLSM method is a simple
      and effective technique for auditory neuron count. It provides a high grade of
      tissue preservation and the automatic stack-generation as well as the counter
      software reduces the effort considerably. In addition this visualisation
      technique offers the potential to detect the position and orientation of cochlear
      implants (CI) within the cochlea and tissue growing in the scala tympani around
      the CI and at the position of the cochleostomy due to the fact that the implant
      does not have to be removed to perform histology as in case of the paraffin
      method.

PMID- 23968823
TI  - Novel hydroxyl tricyclics (e.g., GSK966587) as potent inhibitors of bacterial
      type IIA topoisomerases.
AB  - During the course of our research to find novel mode of action antibacterials, we
      discovered a series of hydroxyl tricyclic compounds that showed good potency
      against Gram-positive and Gram-negative pathogens. These compounds inhibit
      bacterial type IIA topoisomerases. Herein we will discuss structure-activity
      relationships in this series and report advanced studies on compound 1
      (GSK966587) which demonstrates good PK and in vivo efficacy properties. X-ray
      crystallographic studies were used to provide insight into the structural basis
      for the difference in antibacterial potency between enantiomers. 

PMID- 23968824
TI  - Design, synthesis and ex vivo evaluation of colon-specific azo based prodrugs of
      anticancer agents.
AB  - Colon-specific azo based prodrugs of anticancer agents like methotrexate (6),
      gemcitabine (7) and analogue of oxaliplatin (RTB-4) (8) were synthesized and
      characterized by modern analytical techniques. The prepared prodrugs were stable
      in acidic (pH 1.2) and basic (pH 7.4) buffers which showed their stability in
      upper GIT environment. Further, an assay was performed which demonstrated the
      presence of azoreductase enzyme in the rat fecal material, rat cecum content and
      other parts of intestinal content which reduce specifically the azo bond and
      release the drug. The in vitro cytotoxicity assay was also performed which
      clearly indicated that these azo based prodrugs are active against human
      colorectal cancer cell lines (COLO 205, COLO 320 DM and HT-29). The release
      behavior of prodrugs (10, 11 and 15) was 60-70% after 24h incubation at 37
      degrees C. Therefore, the synthesized azo linked prodrugs of methotrexate,
      gemcitabine and RTB-4 are the potential candidates for colon targeted drug
      delivery system with minimal undesirable side effects. 

PMID- 23968825
TI  - Design, synthesis and biological studies of survivin dimerization modulators that
      prolong mitotic cycle.
AB  - Survivin, a member of the inhibitor of apoptosis protein (IAP) family proteins,
      has essential roles in cell division and inhibition of apoptosis. Several
      clinical studies in cancer patients have shown that the elevated levels of
      survivin correlate with aggressiveness of the disease and resistance to radiation
      and chemotherapeutic treatments. Survivin is an integral component of chromosomal
      passenger complex (CPC) where it binds to borealin and INCENP through its
      dimerization interface. Thus, disruption of functional survivin along its dimer
      interface with a small molecule is hypothesized to inhibit the proliferation of
      cancer cells and sensitize them to therapeutic agents and radiation. Recently, a
      small molecule (Abbott8) was reported to bind at the dimerization interface of
      survivin. Further development of this compound was accomplished by computational
      modeling of the molecular interactions along the dimerization interface, which
      has led to the design of promising survivin dimerization modulators. Two of the
      most potent survivin modulators, LLP3 and LLP9 at concentrations between 50 and
      100nM, caused delay in mitotic progression and major mitotic defects in
      proliferating human umbilical vein endothelial cells (HUVEC) and prostate cancer
      cells (PC3). 

PMID- 23968827
TI  - Impact of universal two-dose vaccination on varicella epidemiology in Navarre,
      Spain, 2006 to 2012.

PMID- 23968826
TI  - Naphthoquinones isolated from Diospyros anisandra exhibit potent activity against
      pan-resistant first-line drugs Mycobacterium tuberculosis strains.
AB  - BACKGROUND AND OBJECTIVES: The recent emergence of multidrug-resistant (MDR),
      extensively drug-resistant (XDR), and totally drug-resistant (TDR) Mycobacterium
      tuberculosis (MTB) strains have further complicated the control of tuberculosis
      (TB). There is an urgent need of new molecules candidates to be developed as
      novel, active, and less toxic anti-tuberculosis (anti-TB) drugs. Medicinal plants
      have been an excellent source of leads for the development of drugs, particularly
      as anti-infective agents. In previous studies, the non-polar extract of Diospyros
      anisandra showed potent anti-TB activity, and three monomeric and five dimeric
      naphthoquinones have been obtained. In this study, we performed bioguided
      chemical fractionation and the isolation of eight naphthoquinones from D.
      anisandra and their evaluation of anti-TB and cytotoxic activities against
      mammalian cells. METHODS: The n-hexane crude extract from the stem bark of the
      plant was obtained by maceration and liquid-liquid fractionation. The isolation
      of naphthoquinones was carried out by chromatographic methods and identified by
      gas chromatography and mass spectroscopy data analysis. Anti-TB activity was
      evaluated against two strains of MTB (H37Rv) susceptible to all five first-line
      anti-TB drugs and a clinical isolate that is resistant to these medications (pan
      resistant, CIBIN 99) by measuring the minimal inhibitory concentration (MIC).
      Cytotoxicity of naphthoquinones was estimated against two mammalian cells, Vero
      line and primary cultures of human peripheral blood mononuclear (PBMC) cells, and
      their selectivity index (SI) was determined. RESULTS: Plumbagin and its dimers
      maritinone and 3,3'-biplumbagin showed the strongest activity against both MTB
      strains (MIC = 1.56-3.33 MUg/mL). The bioactivity of maritinone and 3,3'
      biplumbagin were 32 times more potent than rifampicin against the pan-resistant
      strain, and both dimers showed to be non-toxic against PBMC and Vero cells. The
      SI of maritinone and 3,3'-biplumbagin on Vero cells was 74.34 and 194.11 against
      sensitive and pan-resistant MTB strains, respectively. CONCLUSION: Maritinone and
      3,3'-biplumbagin possess a very interesting potential for development as new
      drugs against M. tuberculosis, mainly resistant profile strains.

PMID- 23968828
TI  - Systematic review of tattoo-associated skin infection with rapidly growing
      mycobacteria and public health investigation of a cluster in Scotland, 2010.

PMID- 23968829
TI  - International infectious disease surveillance during the London Olympic and
      Paralympic Games 2012: process and outcomes.

PMID- 23968830
TI  - Development of cholesteryl peptide micelles for siRNA delivery.
AB  - Despite the rapid progress in the siRNA field, developing a safe and efficient
      delivery system of siRNA remains to be an obstacle in the therapeutical
      application of siRNA. The purpose of this study is to develop an efficient
      peptide-based siRNA delivery system for cancer therapy. To this end, cholesterol
      was conjugated to a series of peptides composed of lysine and histidine residues.
      The resultant cholesteryl peptides were characterized, and their potential for
      siRNA delivery was evaluated. Our results indicate that short peptides (11-21
      mer) composed of various numbers of lysine and histidine residues alone are not
      sufficient to mediate efficient siRNA delivery. However, the amphiphilic
      cholesteryl peptides can self-assemble to form a micelle-like structure in
      aqueous solutions, which significantly promotes the siRNA condensation capability
      of the peptides. The cholesteryl peptides form stable complex with siRNA and
      effectively protect siRNA from degradation in rat serum up to three days.
      Furthermore, the cholesteryl peptides efficiently transfect siRNA into different
      cancer cells and trigger potent gene silencing effect, whereas peptides without
      cholesterol modification cannot deliver siRNA into the cells. In addition, one of
      the cholesteryl peptides Chol-H3K2s displays comparable cellular uptake and gene
      silencing effect but less cytotoxicity compared with branched polyethylenimine
      (bPEI) and Lipofectamine-2000. Our results reveal that the cholesteryl peptides
      possess great potential as an efficient siRNA delivery system. 

PMID- 23968832
TI  - Ventral medial nucleus neurons send thalamocortical afferents more widely and
      more preferentially to layer 1 than neurons of the ventral anterior-ventral
      lateral nuclear complex in the rat.
AB  - Not only inhibitory afferent-dominant zone (IZ) of the ventral anterior-ventral
      lateral thalamic complex (VA-VL) but also the ventral medial nucleus (VM) is
      known to receive strong inputs from the basal ganglia and send axons to motor
      areas. We previously reported differences in axonal arborization between IZ
      neurons and the other VA-VL neurons in rats by single-neuron tracing with viral
      vectors. In the present study, the axonal arborization of single VM neurons was
      visualized by the same method, and compared with that of IZ neurons. VM neurons
      formed fewer axon collaterals in the striatum, but sent axon fibers more widely
      and more preferentially (79% of fibers) to layer 1 of cortical areas than IZ
      neurons. Furthermore, the VM seemed to contain at least 2 types of neurons; a
      major population of VM neurons sent axon fibers principally to motor-associated
      areas as VA-VL neurons did, and the other population projected mainly to orbital
      or cingulate areas. Although both VM and IZ neurons receive strong basal ganglia
      inputs, these results suggest that VM neurons, at a single neuron level,
      innervate the apical dendrites of cortical pyramidal neurons more intensely and
      more widely than IZ neurons. 

PMID- 23968831
TI  - Fine-tuning of neurogenesis is essential for the evolutionary expansion of the
      cerebral cortex.
AB  - We used several animal models to study global and regional cortical surface
      expansion: The lissencephalic mouse, gyrencephalic normal ferrets, in which the
      parietal cortex expands more than the temporal cortex, and moderately
      lissencephalic ferrets, showing a similar degree of temporal and parietal
      expansion. We found that overall cortical surface expansion is achieved when
      specific events occur prior to surpragranular layer formation. (1) The
      subventricular zone (SVZ) shows substantial growth, (2) the inner SVZ contains an
      increased number of outer radial glia and intermediate progenitor cells
      expressing Pax6, and (3) the outer SVZ contains a progenitor cell composition
      similar to the combined VZ and inner SVZ. A greater parietal expansion is also
      achieved by eliminating the latero-dorsal neurogenic gradient, so that
      neurogenesis displays a similar developmental degree between parietal and
      temporal regions. In contrast, mice or lissencephalic ferrets show more advanced
      neurogenesis in the temporal region. In conclusion, we propose that global and
      regional cortical surface expansion rely on similar strategies consisting in
      altering the timing of neurogenic events prior to the surpragranular layer
      formation, so that more progenitor cells, and ultimately more neurons, are
      produced. This hypothesis is supported by findings from a ferret model of
      lissencephaly obtained by transiently blocking neurogenesis during the formation
      of layer IV. 

PMID- 23968833
TI  - ARX regulates cortical intermediate progenitor cell expansion and upper layer
      neuron formation through repression of Cdkn1c.
AB  - Mutations in the Aristaless-related homeobox (ARX) gene are found in a spectrum
      of epilepsy and X-linked intellectual disability disorders. During development
      Arx is expressed in pallial ventricular zone (VZ) progenitor cells where the
      excitatory projection neurons of the cortex are born. Arx(-/Y) mice were shown to
      have decreased proliferation in the cortical VZ resulting in smaller brains;
      however, the basis for this reduced proliferation was not established. To
      determine the role of ARX on cell cycle dynamics in cortical progenitor cells, we
      generated cerebral cortex-specific Arx mouse mutants (cKO). The loss of pallial
      Arx resulted in the reduction of cortical progenitor cells, particularly the
      proliferation of intermediate progenitor cells (IPCs) was affected. Later in
      development and postnatally cKO brains showed a reduction of upper layer but not
      deeper layer neurons consistent with the IPC defect. Transcriptional profile
      analysis of E14.5 Arx-ablated cortices compared with control revealed that
      CDKN1C, an inhibitor of cell cycle progression, is overexpressed in the cortical
      VZ and SVZ of Arx KOs throughout corticogenesis. We also identified ARX as a
      direct regulator of Cdkn1c transcription. Together these data support a model
      where ARX regulates the expansion of cortical progenitor cells through repression
      of Cdkn1c. 

PMID- 23968835
TI  - Developmental reduction of asynchronous GABA release from neocortical fast
      spiking neurons.
AB  - Delayed asynchronous release (AR) evoked by bursts of presynaptic action
      potentials (APs) occurs in certain types of hippocampal and neocortical
      inhibitory interneurons. Previous studies showed that AR provides long-lasting
      inhibition and desynchronizes the activity in postsynaptic cells. However,
      whether AR undergoes developmental change remains unknown. In this study, we
      performed whole-cell recording from fast-spiking (FS) interneurons and pyramidal
      cells (PCs) in prefrontal cortical slices obtained from juvenile and adult rats.
      In response to AP trains in FS neurons, AR occurred at their output synapses
      during both age periods, including FS autapses and FS-PC synapses; however, the
      AR strength was significantly weaker in adults than that in juveniles. Further
      experiments suggested that the reduction of AR in adult animals could be
      attributable to the rapid clearance of residual Ca(2+) from presynaptic
      terminals. Together, our results revealed that the AR strength was stronger at
      juvenile but weaker in adult, possibly resulting from changes in presynaptic
      Ca(2+) dynamics. AR changes may meet the needs of the neural network to generate
      different types of oscillations for cortical processing at distinct behavioral
      states. 

PMID- 23968834
TI  - Induction of motor associative plasticity in the posterior parietal cortex
      primary motor network.
AB  - There is anatomical and functional connectivity between the primary motor cortex
      (M1) and posterior parietal cortex (PPC) that plays a role in sensorimotor
      integration. In this study, we applied corticocortical paired-associative stimuli
      to ipsilateral PPC and M1 (parietal ccPAS) in healthy right-handed subjects to
      test if this procedure could modulate M1 excitability and PPC-M1 connectivity.
      One hundred and eighty paired transcranial magnetic stimuli to the PPC and M1 at
      an interstimulus interval (ISI) of 8 ms were delivered at 0.2 Hz. We found that
      parietal ccPAS in the left hemisphere increased the excitability of conditioned
      left M1 assessed by motor evoked potentials (MEPs) and the input-output curve.
      Motor behavior assessed by the Purdue pegboard task was unchanged compared with
      controls. At baseline, conditioning stimuli over the left PPC potentiated MEPs
      from left M1 when ISI was 8 ms. This interaction significantly attenuated at 60
      min after left parietal ccPAS. Additional experiments showed that parietal ccPAS
      induced plasticity was timing-dependent, was absent if ISI was 100 ms, and could
      also be seen in the right hemisphere. Our results suggest that parietal ccPAS can
      modulate M1 excitability and PPC-M1 connectivity and is a new approach to modify
      motor excitability and sensorimotor interaction. 

PMID- 23968836
TI  - A forward genetic screen in mice identifies mutants with abnormal cortical
      patterning.
AB  - Formation of a 6-layered cortical plate and axon tract patterning are key
      features of cerebral cortex development. Abnormalities of these processes may be
      the underlying cause for a range of functional disabilities seen in human
      neurodevelopmental disorders. To identify mouse mutants with defects in cortical
      lamination or corticofugal axon guidance, N-ethyl-N-nitrosourea (ENU) mutagenesis
      was performed using mice expressing LacZ reporter genes in layers II/III and V of
      the cortex (Rgs4-lacZ) or in corticofugal axons (TAG1-tau-lacZ). Four lines with
      abnormal cortical lamination have been identified. One of these was a splice site
      mutation in reelin (Reln) that results in a premature stop codon and the
      truncation of the C-terminal region (CTR) domain of reelin. Interestingly, this
      novel allele of Reln did not display cerebellar malformation or ataxia, and this
      is the first report of a Reln mutant without a cerebellar defect. Four lines with
      abnormal cortical axon development were also identified, one of which was found
      by whole-genome resequencing to carry a mutation in Lrp2. These findings
      demonstrated that the application of ENU mutagenesis to mice carrying transgenic
      reporters marking cortical anatomy is a sensitive and specific method to identify
      mutations that disrupt patterning of the developing brain. 

PMID- 23968838
TI  - Rescue of NMDAR-dependent synaptic plasticity in Fmr1 knock-out mice.
AB  - Fragile X Syndrome (FXS) is the most common form of inherited intellectual
      disability and results from a loss of Fragile X mental retardation protein
      (FMRP). FMRP is important for mRNA shuttling and translational control and binds
      to proteins important for synaptic plasticity. Like many developmental disorders,
      FXS is associated with alterations in synaptic plasticity that may impair
      learning and memory processes in the brain. However, it remains unclear whether
      FMRP plays a ubiquitous role in synaptic plasticity in all brain regions. We
      report that a loss of FMRP leads to impairments in N-methyl-D-aspartate receptor
      (NMDAR)-dependent synaptic plasticity in the dentate gyrus (DG), but not in the
      cornu ammonis area 1 (CA1) subregion of the hippocampus of adult mice. DG
      specific deficits are accompanied by a significant reduction in NMDAR GluN1,
      GluN2A, and GluN2B subunit levels and reduced serine 831 GluA1 phosphorylation
      specifically in this region. Importantly, we demonstrate that treatment with
      NMDAR co-agonists (glycine or D-serine) independently rescue impairments in NMDAR
      dependent synaptic plasticity in the DG of the Fragile X mental retardation 1
      (Fmr1) knockout mouse. These findings implicate the NMDAR in the pathophysiology
      of FXS and suggest that indirect agonists of the NMDAR may be a successful
      therapeutic intervention in FXS.

PMID- 23968837
TI  - Resting-state striato-frontal functional connectivity is sensitive to DAT1
      genotype and predicts executive function.
AB  - Individual differences in striatal dopamine (DA) signaling have been associated
      both with individual differences in executive function in healthy individuals and
      with risk for psychiatric disorders defined by executive dysfunction. We used
      resting-state functional connectivity in 50 healthy adults to examine whether a
      polymorphism of the dopamine transporter gene (DAT1), which regulates striatal DA
      function, affects striatal functional connectivity in healthy adults, and whether
      that connectivity predicts executive function. We found that 9/10 heterozygotes,
      who are believed to have higher striatal DA signaling, demonstrated stronger
      connectivity between dorsal caudate (DC) and insular, dorsal anterior cingulate,
      and dorsolateral prefrontal regions, as well as between ventral striatum and
      ventrolateral prefrontal cortex, than 10/10 homozygotes. Across subjects,
      stronger DC-seeded connectivity predicted superior N-back working memory
      performance, while stronger ventral striatum-seeded connectivity predicted
      reduced impulsivity in everyday life. Further, mediation analysis suggested that
      connectivity strength mediated relationships between DAT1 genotype and behavior.
      These findings suggest that resting-state striato-frontal connectivity may be an
      endophenotype for executive function in healthy individuals. 

PMID- 23968839
TI  - Hippocampal-cerebellar interaction during spatio-temporal prediction.
AB  - The hippocampus and cerebellum play a role in the process of temporal memory
      formation. The interaction between these brain regions during the prediction of
      motor executions nevertheless remains unclear. Using fMRI, we show here that the
      hippocampus and cerebellum are co-activated during a timing-dependent task that
      requires accurate prediction timing of finger movements following preceding
      visual cues, but not during 2 control tasks: a reaction task requiring identical
      coordination of individual and combined fingers without predicting the motor
      timing, or an imagery task. In addition, functional connectivity analyses reveal
      that the hippocampus showed increased functional connectivity with the bilateral
      hemispheres of the cerebellum. These results suggest that hippocampal-cerebellar
      interplay occurs during spatio-temporal prediction of movements on the basis of
      visuomotor integration. 

PMID- 23968840
TI  - Individual differences in laughter perception reveal roles for mentalizing and
      sensorimotor systems in the evaluation of emotional authenticity.
AB  - Humans express laughter differently depending on the context: polite titters of
      agreement are very different from explosions of mirth. Using functional MRI, we
      explored the neural responses during passive listening to authentic amusement
      laughter and controlled, voluntary laughter. We found greater activity in
      anterior medial prefrontal cortex (amPFC) to the deliberate, Emitted Laughs,
      suggesting an obligatory attempt to determine others' mental states when laughter
      is perceived as less genuine. In contrast, passive perception of authentic Evoked
      Laughs was associated with greater activity in bilateral superior temporal gyri.
      An individual differences analysis found that greater accuracy on a post hoc test
      of authenticity judgments of laughter predicted the magnitude of passive
      listening responses to laughter in amPFC, as well as several regions in
      sensorimotor cortex (in line with simulation accounts of emotion perception).
      These medial prefrontal and sensorimotor sites showed enhanced positive
      connectivity with cortical and subcortical regions during listening to
      involuntary laughter, indicating a complex set of interacting systems supporting
      the automatic emotional evaluation of heard vocalizations. 

PMID- 23968841
TI  - High temperature aqueous ammonia pretreatment and post-washing enhance the high
      solids enzymatic hydrolysis of corn stover.
AB  - Aqueous ammonia pretreatment was optimized and the limiting factors in high
      solids enzymatic hydrolysis were assessed. The recommended pretreatment condition
      to achieve high enzymatic yield was: 180  degrees C, 20% (w/w) ammonia, 30 min,
      and 20% solids content. FT-IR and GC-MS results indicated that most of the lignin
      was degraded to soluble fragments after pretreatment. The pretreated solids after
      post-washing showed higher enzymatic digestibility at high solids loading than
      that without washing. The washed solids required lower cellulase and xylanase
      dosage than unwashed solids to achieve high sugar yield. Enzymatic conversions
      were declined with the increased solids loading of pretreated solids, pretreated
      washed solids, and filter papers. The results indicated that solids loading in
      enzymatic hydrolysis was an important factor affecting sugar yield. The
      increasing concentration of glucose and ligno-phenolics mainly inhibited the
      enzymatic hydrolysis of aqueous ammonia pretreated corn stover.

PMID- 23968842
TI  - Altered EEG lagged coherence during rest in obsessive-compulsive disorder.
AB  - OBJECTIVE: Functional magnetic resonance imaging (fMRI) studies found alterations
      of functional connectivity in obsessive compulsive disorder (OCD). However, there
      is little knowledge about region of interest (ROI) based electroencephalogram
      (EEG) connectivity, i.e. lagged non-linear and linear coherence in OCD. Goal of
      this study was to compare these EEG measures during rest and at different
      vigilance stages between patients and healthy controls (HC). METHODS: A 15 min
      resting-state EEG was recorded in 30 unmedicated patients and 30 matched HC.
      Intracortical lagged non-linear coherence of the main EEG-frequency bands within
      a set of frontal ROIs and within the default mode network (DMN) were computed and
      compared using intracortical exact low resolution electromagnetic tomography
      (eLORETA) software. RESULTS: Lagged non-linear but not linear coherence was
      significantly decreased for patients in comparison to HC for the beta 2 frequency
      between frontal brain areas but not within the DMN. When analysing separate EEG
      vigilance stages, only high vigilance stages yielded decreased frontal phase
      synchronisation at beta and theta frequencies. CONCLUSIONS: The results underline
      an altered neuronal communication within frontal brain areas during rest in OCD.
      SIGNIFICANCE: These findings encourage further research on connectivity measures
      as possible biomarkers for physiological homogeneous subgroups.

PMID- 23968843
TI  - EEG connectome: a new candidate for endophenotypes.

PMID- 23968844
TI  - Reply to "Parkinson's disease, L-Dopa and "express" saccades: superior colliculus
      dyskinesias?".

PMID- 23968845
TI  - Low frequency mu-like activity characterizes cortical rhythms in epilepsy due to
      ring chromosome 20.
AB  - OBJECTIVES: To evaluate the spectral and spatial features of the cortical rhythms
      in patients affected by ring chromosome 20 - [r(20)]-syndrome. METHODS: Twelve
      patients with [r(20)] syndrome were studied. As controls we enrolled 12 patients
      with idiopathic generalized epilepsy (IGE) and 12 healthy volunteers (HV). Blind
      source separation, spectral analyses and source reconstruction were applied in
      all cases in order to identify reliable spatio-temporal patterns of cortical
      activity. RESULTS: A theta-delta EEG rhythm was identified in [r(20)] patients,
      with spectral peak ranging between 3 and 7Hz and whose generators mapped over the
      sensory-motor cortices. A second peak laying at a frequency about double with
      respect to the first one was present in 6 cases. Analogue methodological approach
      in HV and IGE groups failed to show similar findings. CONCLUSIONS: EEG of [r(20)]
      patients reveals the existence of a highly reproducible EEG pattern arising from
      the sensory-motor system. SIGNIFICANCE: The recognition of this peculiar EEG
      pattern could help the diagnostic work-up. Additionally, our findings supports
      the existence of a parallelism between this EEG trait and the physiological "mu"
      rhythm which is generate by the sensory-motor system. Such link suggests a
      sensory-motor system dysfunction in [r(20)] patients.

PMID- 23968846
TI  - Immunomodulatory effects of dexamethasone on gene expression of cytokine and
      stress hormone receptors in peripheral blood mononuclear cells.
AB  - Glucocorticoid (GC) such as cortisol in humans is a major stress hormone and can
      influence immunomodulation through various mechanisms including impact on
      regulatory T-cell (RTC) elements and changes in Th1/Th2 cytokine balance. In this
      study, we sought to determine the immunomodulatory effects of GC equivalent
      dexamethasone (DEX) at various concentrations (10(-7), 10(-8), and 10(-9) M) on
      gene expression of RTC, cytokine receptors and stress hormone receptors from
      normal human peripheral blood mononuclear cells (PBMC) in an in vitro stress
      model in 24 h (acute stress) vs 11-day (chronic stress) cultures. Results
      revealed that the mRNA of forkhead box P3 (FoxP3) was significantly decreased at
      24 h with 10(-7) and 10(-8) M DEX. After 11 days, FoxP3 expression in the 10(-8)
      M DEX cultures had returned to baseline but was still down-regulated with 10(-7)
      M DEX. GC receptor (GR) mRNA decreased and beta2 adrenergic receptor (beta 2AR)
      mRNA increased significantly after 24 h exposure to DEX. These changes had
      returned to baseline in the 11-day cultures. The IFN-gammaR/IL-4R ratio, an
      alternative marker for Th1/Th2 balance, was significantly increased at 24 h and
      decreased after 11-day cultures with 10(-7) and 10(-8) M DEX compared to control
      cultures. These findings further contribute to our understanding of the
      mechanisms associated with the effects of acute vs. chronic stress on normal
      immune balance.

PMID- 23968847
TI  - Influences of cerebral stent implantation on CD4+ CD25+ FOXP3+ Treg, Th1 and Th17
      cells.
AB  - Stent implantation is primarily used for the treatment of artery stenosis.
      However, the application and use of stent struts induces local and systemic
      inflammation, leading to intractable neointimal hyperplasia. CD4(+) T cells are
      involved in artery stenosis diseases, but little is known about the influence of
      the CD4(+) T cells on the inflammation reaction after stent implantation. In this
      study, we analyzed the frequency of signature transcription factors and
      proinflammatory cytokine expression from each subtype of CD4(+) T cells in 50
      patients receiving intracranial or cervical stent implantations from December
      2011 to June 2012. The results showed that the frequency of signature
      transcription factor/cytokine production in Treg cells was reduced in the first
      week and returned to control levels at 3 months after stent implantation.
      However, we observed opposite trends for Th17 cells, showing increased signature
      transcription factor/cytokine production during the acute phase, which returned
      to control levels after 3 months. No significant difference in the frequency of
      signature transcription factor/cytokine expression was observed in Th1 cells from
      patients before and after stent implantation. We speculate that the maintenance
      of the frequency and function of Tregs controls the inflammatory response, which
      otherwise induces acute inflammation after stent implantation.

PMID- 23968848
TI  - An approach to local immunotoxicity induced by adjuvanted vaccines.
AB  - The occurrence of injection site reactions following immunization is the most
      frequently reported toxicity manifestation of vaccines; however, the different
      types of local reactions and the different mechanisms involved are still unclear.
      Here, the current advances in adjuvants and the role that adjuvants play in local
      reactions are reviewed. The role of adjuvants in the formation of the loco
      regional complex (LRC), which consists of the injection site, draining lymphatic
      vessels and regional lymph nodes, is also discussed. Finally, strategies and
      recommendations for the rational design of adjuvanted vaccines are discussed,
      with a particular interest in the reduction of local inflammation. 

PMID- 23968849
TI  - Patient-related factors may affect the outcome of neuropsychological
      rehabilitation in multiple sclerosis.
AB  - OBJECTIVE: The aim of this study was to identify factors associated with
      neuropsychological rehabilitation outcome in patients with multiple sclerosis
      (MS). METHODS: Ninety-eight relapsing-remitting MS patients received multimodal
      neuropsychological intervention (attention retraining, teaching compensatory
      strategies, psychoeducation, psychological support, and homework assignments)
      conducted once a week in 60-minute sessions during thirteen consecutive weeks.
      The evaluated factors included: 1) patient-related (baseline objective and
      subjective cognitive performance, mood, fatigue, as well as demographic factors);
      2) illness-related (duration and severity of the disease); and 3) intervention
      related factors (amount of computer-based attention exercises and homework
      assignments, therapist's evaluation of the benefit, and therapist). RESULTS:
      Patient-related factors affected rehabilitation outcome, whereas illness- and
      intervention-related factors did not. The results showed that especially MS
      patients with male gender and more severe attentional deficits benefitted from
      the intervention. CONCLUSION: Patient-related factors may affect
      neuropsychological rehabilitation outcome in MS.

PMID- 23968850
TI  - Seizure semiology reflects spread from frontal to temporal lobe: evolution of
      hyperkinetic to automotor seizures as documented by invasive EEG video
      recordings.
AB  - This patient report demonstrates the importance of seizure evolution in the
      localising value of seizure semiology. Spread of epileptic activity from frontal
      to temporal lobe, as demonstrated by invasive recordings, was reflected by change
      from hyperkinetic movements to arrest of activity with mild oral and manual
      automatisms. [Published with video sequences]. 

PMID- 23968851
TI  - The effect of substrate surface nanotopography on the behavior of multipotnent
      mesenchymal stromal cells and osteoblasts.
AB  - Hexagonally arranged Gold nanoparticles with controllable diameters and inter
      particle distances were deposited on thick SiO2 layers on top of Si wafers and
      used as masks during subsequent reactive ion etching. In this way, arrays of
      nanopillars are obtained with well-defined diameters (10/30 nm), inter-pillar
      distances (50-120 nm) and heights (20-35 nm), all on the nanoscale. Such
      nanotopographies served as substrate for multipotent mesenchymal stromal cells
      (MSC) and human osteoblasts (OB) allowing to study cellular responses to purely
      topographically patterned interfaces. Focus was put on adhesion, proliferation
      and differentiation of the cells. It turned out experimentally that adhesion is
      comparable for both cell types practically independent of topographical details
      at the substrate surface. Topography induced proliferation enhancement, however,
      is again independent of geometrical details in case of MSC, but significantly
      sensitive to pillar height in case of OB with a clear preference towards short
      nanopillars (20 nm). A high sensitivity to topographic details is also observed
      for osteogenic differentiation of MSC, in that case with a preference towards
      higher nanopillars (50 nm). The present experimental data also allow the
      important conclusion that cell proliferation and differentiation can be optimized
      simultaneously by fine-tuning nanoscaled topographical parameters.

PMID- 23968852
TI  - Brain-targeting delivery for RNAi neuroprotection against cerebral ischemia
      reperfusion injury.
AB  - Nanoparticles (NPs) with modification of brain-targeting molecules have been
      extensively exploited for therapeutic gene delivery across the blood-brain
      barrier (BBB). As one of the effective RNA interference (RNAi) approaches, short
      hairpin RNA (shRNA) has been proved to be promising in the field of gene therapy.
      Apoptosis signal-regulating kinase 1 (Ask1) has been reported to be an important
      target for gene therapy against cerebral ischemia reperfusion injury. In this
      study, dendrigraft poly-l-lysine (DGL) was decorated by dermorphin (a MU-opiate
      receptor agonist) through PEG for efficient brain-targeting, then complexed with
      anti-Ask1 shRNA plasmid DNA, yielding the DGL-PEG-dermorphin/shRNA NPs. The DGL
      PEG-dermorphin/shRNA NPs were characterized and estimated the brain-targeting
      ability. In vitro, increased cellular uptake and transfection efficiency were
      explored; in vivo, preferable accumulation and gene transfection in brain were
      showed in images. The DGL-PEG-dermorphin/shRNA NPs also revealed high efficiency
      of neuroprotection. As a result of RNAi, corresponding mRNA was distinctly
      degraded, expression of Ask1 protein was obviously suppressed, apoptotic cell
      death was apparently decreased and cerebral infarct area was significantly
      reduced. Above all, DGL-PEG-dermorphin/shRNA NPs were proved to be efficient and
      safe for brain-targeting RNAi neuroprotection against cerebral ischemia
      reperfusion injury. 

PMID- 23968853
TI  - Immunotherapy of CD30-expressing lymphoma using a highly stable ssDNA aptamer.
AB  - CD30 is highly expressed on Hodgkins lymphoma and anaplastic large cell lymphoma,
      making it an attractive target for therapy. We describe the generation of serum
      stabilized ssDNA aptamers that bind CD30 via a hybrid SELEX methodology. The
      selected aptamer bound CD30 with high affinity and specificity. Further
      optimization of the aptamer led to a short, truncated variant with a 50-fold
      higher affinity than its longer counterpart. The multivalent aptamer was able to
      induce oligomerization of CD30 receptors and, in effect, activate downstream
      signaling, which led to apoptosis of ALCL cells. Immunotherapy using aptamer
      based co-stimulation provides an alternative to antibodies, and has potential to
      transform cancer treatment. 

PMID- 23968854
TI  - Anti-biofouling conducting polymer nanoparticles as a label-free optical contrast
      agent for high resolution subsurface biomedical imaging.
AB  - Optical coherence tomography (OCT) is a modern high resolution subsurface medical
      imaging technique. Herein we describe: (i) the synthesis of a thiophene
      functionalized oligo(ethylene glycol) methacrylate (OEGMA)-based statistical
      copolymer, denoted poly(2TMOI-OEGMA); (ii) the preparation of sterically
      stabilized polypyrrole (PPy) nanoparticles of approximately 60 nm diameter; (iii)
      the evaluation of these nanoparticles as a NIR-absorbing optical contrast agent
      for high-resolution OCT imaging. We show that poly(2TMOI-OEGMA)-stabilized PPy
      nanoparticles exhibit similar optical properties to poly(vinyl alcohol) (PVA)
      stabilized PPy nanoparticles of comparable size prepared using commercially
      available PVA. Spectroscopic measurements and Mie calculations indicate that both
      types of PPy nanoparticles strongly absorb NIR radiation above 1000 nm,
      suggesting their potential use as OCT contrast agents. In vitro OCT studies
      indicate that both types of PPy nanoparticles reduce NIR backscattering within
      homogeneous intralipid tissue phantoms, offering almost identical contrast
      performance in this medium. However, PVA-stabilized PPy nanoparticles became
      colloidally unstable when dispersed in physiological buffer and immersed in a
      solid biotissue phantom and hence failed to generate a strong contrast effect. In
      contrast, the poly(2TMOI-OEGMA)-stabilized PPy nanoparticles remained well
      dispersed and hence exhibited a strong rapid onset contrast effect within the
      biotissue phantom under identical physiological conditions. Ex vivo studies
      performed on excised chicken and porcine skin tissue demonstrated that topical
      administration of a low concentration of poly(2TMOI-OEGMA)-stabilized PPy
      nanoparticles rapidly enhances OCT image contrast in both cases, allowing key
      tissue features to be readily identified. 

PMID- 23968855
TI  - Rapid tissue engineering of biomimetic human corneal limbal crypts with 3D niche
      architecture.
AB  - Limbal epithelial stem cells are responsible for the maintenance of the human
      corneal epithelium and these cells reside in a specialised stem cell niche. They
      are located at the base of limbal crypts, in a physically protected
      microenvironment in close proximity to a variety of neighbouring niche cells.
      Design and recreation of elements of various stem cell niches have allowed
      researchers to simplify aspects of these complex microenvironments for further
      study in vitro. We have developed a method to rapidly and reproducibly create
      bioengineered limbal crypts (BLCs) in a collagen construct using a simple one
      step method. Liquid is removed from collagen hydrogels using hydrophilic porous
      absorbers (HPAs) that have custom moulded micro-ridges on the base. The resulting
      topography on the surface of the thin collagen constructs resembles the
      dimensions of the stromal crypts of the human limbus. Human limbal epithelial
      cells seeded onto the surface of the constructs populate these BLCs and form
      numerous layers with a high proportion of the cells lining the crypts expressing
      putative stem cell marker, p63alpha. The HPAs are produced using a moulding
      process that is flexible and can be adapted depending on the requirements of the
      end user. Creation of defined topographical features using this process could be
      applicable to numerous tissue-engineering applications where varied 3-dimensional
      niche architectures are required. 

PMID- 23968856
TI  - Photo-activatable ternary complex based on a multifunctional shielding material
      for targeted shRNA delivery in cancer treatment.
AB  - A photo-activatable ternary complex (PTC) consisting of multifunctional shielding
      material (MSM) with photosensitizer (PS)-conjugated chondroitin sulfate and
      polyethyleneimine based binary complexes containing epidermal growth factor
      receptor (EGFR)-shRNA delivery for CD44 targeted cancer therapy has been
      developed. The PTC has a negative surface charge of -37.9 mV, and a size of
      approximately 90 nm, and the ternary complexes were found to be stable against
      plasma proteins. The stable nanostructure of PTC especially could enable CD44
      receptor mediated tumor-targeted delivery and PS-mediated endosomal disruption
      for efficient gene silencing, and an enhanced rate of cancer cell death was
      achieved both in vitro and in vivo. This suggests that PTC could represent a
      promising strategy for the delivery of other therapeutic genes for cancer
      therapy. 

PMID- 23968858
TI  - Monitoring the activity of single translocons.
AB  - Recent studies introduced a novel view that the SecYEG translocon functions as a
      monomer and interacts with the dimeric SecA ATPase, which fuels the preprotein
      translocation reaction. Here, we used nanodisc-reconstituted SecYEG to
      characterize the functional properties of single copies of the translocon. Using
      a method based on intermolecular Forster resonance energy transfer, we show for
      the first time that isolated nanodisc-reconstituted SecYEG monomers support
      preprotein translocation. When several copies of SecYEG were co-reconstituted
      within a nanodisc, no change in translocation kinetics was observed, suggesting
      that SecYEG oligomers do not facilitate enhanced translocation. In contrast,
      nanodisc-reconstituted monomers of the PrlA4 variant of SecYEG showed increased
      translocation rates. Experiments based on intramolecular Forster resonance energy
      transfer within the nanodisc-isolated monomeric SecYEG demonstrated a nucleotide
      dependent opening of the channel upon interaction with SecA. In conclusion, the
      nanodisc-reconstituted SecYEG monomers are functional for preprotein
      translocation and provide a new prospect for single-molecule analysis of dynamic
      aspects of protein translocation. 

PMID- 23968857
TI  - A DNA microarray-based analysis of immune-stimulatory and transcriptional
      responses of dendritic cells to KALA-modified nanoparticles.
AB  - Technologies for the transfection of antigen-encoding genes into the dendritic
      cells, and subsequent immune-activation are both prerequisites for a successful
      DNA vaccine. We herein report on the density-dependent enhancement of transgene
      expression by the simple modification by stearyl-conjugated KALA, an alpha
      helical peptide (STR-KALA), onto a lipid envelope-type nanoparticle (the R8-MEND,
      an octaarginine-modified multifunctional envelope-type nano device). The enhanced
      transgene expression in the KALA-modified R8-MEND (R8/KALA-MEND) cannot be
      explained by cellular uptake and nuclear delivery efficacy. Thus, the post
      nuclear delivery process (i.e. transcription), but not intracellular trafficking
      processes attributed the enhanced transfection efficacy. Microarray analyses
      revealed that transfection with the R8/KALA-MEND resulted in a greater
      perturbation in host genes expression in comparison with the R8-MEND and that
      this effect was time-dependent. Further pathway analyses in the category of
      transcription-related genes and a gene ontology analysis indicated that the
      R8/KALA-MEND stimulated the expression of transcription factors that are closely
      related to immune-activation (i.e. NF-kB and STAT). Inhibition of the
      transfection efficacy by blockage of the STAT pathways revealed that the enhanced
      transcription activity is the result of immune-stimulation. Collectively, the
      R8/KALA-MEND mounts a "switch-on" function that triggers signal transduction
      forward to the immune-stimulation analogous to an adjuvant, and consequently
      elicits active transcription. 

PMID- 23968859
TI  - Understanding molecular effects of naturally occurring genetic differences.

PMID- 23968860
TI  - Elevated levels of adiponectin and other cytokines in drug naive, first episode
      schizophrenia patients with normal weight.
AB  - OBJECTIVE: The study was to examine the levels of adiponectin (APN) and other
      cytokines, and body metabolism in drug naive, first episode schizophrenia
      patients with normal weight. METHODS: Ninety-six drug naive, first episode
      schizophrenia patients with normal weight (SZ group), 60 healthy individuals with
      normal weight (control group), and 60 overweight or obese but otherwise healthy
      individuals (obesity group) were enrolled in the study. Serum levels of
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha
      (TNF-alpha), and APN were measured using enzyme linked immunosorbent assay
      (ELISA). Glucose oxidase was used to measure plasma glucose level. Lipid levels
      were measured using the enzymatic colorimetric method. RESULTS: Serum levels of
      IL-1beta, IL-6 and TNF-alpha in both the SZ group and the obesity group were
      significantly higher than those in the control group (p's<0.001). There were no
      significant differences between the SZ group and the obesity group on those
      cytokines (p's>0.05). In addition, the levels of APN were significantly higher in
      the SZ group (p<0.001), and significantly lower in the obesity group (p<0.01)
      compared with the control group. Further, there were significant positive
      relationships between levels of APN and levels of other cytokines within the SZ
      group (p's<0.05); in contrast, there were significant negative relationships
      between levels of APN and levels of other cytokines within the obesity group
      (p's<0.05). Fasting serum levels of glucose, LDL, triglycerides and total
      cholesterol were significantly higher, and fasting serum levels of HDL were
      significantly lower in the obesity group compared with the other two groups
      (p's<0.01). There were no significant differences in any of the metabolic
      parameters between the control group and the SZ group (p's>0.05). CONCLUSIONS:
      Drug naive, first episode schizophrenia patients with normal weight seem to
      present an up-regulated inflammatory status as reflected by elevated levels of IL
      1beta, IL-6, and TNF-alpha. APN may play a unique pro-inflammatory role in this
      patient population. Implications of the findings in relation to the pathogenesis
      of schizophrenia and the vulnerability for metabolic problems were discussed.

PMID- 23968861
TI  - Charge transfer through DNA/DNA duplexes and DNA/RNA hybrids: complex theoretical
      and experimental studies.
AB  - Oligonucleotides conduct electric charge via various mechanisms and their
      characterization and understanding is a very important and complicated task. In
      this work, experimental (temperature dependent steady state fluorescence
      spectroscopy, time-resolved fluorescence spectroscopy) and theoretical (Density
      Functional Theory) approaches were combined to study charge transfer processes in
      short DNA/DNA and RNA/DNA duplexes with virtually equivalent sequences. The
      experimental results were consistent with the theoretical model - the delocalized
      nature of HOMO orbitals and holes, base stacking, electronic coupling and
      conformational flexibility formed the conditions for more effective short
      distance charge transfer processes in RNA/DNA hybrids. RNA/DNA and DNA/DNA charge
      transfer properties were strongly connected with temperature affected structural
      changes of molecular systems - charge transfer could be used as a probe of even
      tiny changes of molecular structures and settings. 

PMID- 23968862
TI  - Extracts from Astragalus membranaceus limit myocardial cell death and improve
      cardiac function in a rat model of myocardial ischemia.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The root of Astragalus membranaceus, known as
      "huang-qi", is one of the most widely used Chinese herbal medicines for the
      prevention and treatment of myocardial ischemic diseases. However, the mechanisms
      governing its therapeutic effects are largely unknown. AIMS OF THE STUDY: The
      aims of the present study were to investigate the cardioprotective effect of the
      root extract of Astragalu membranaceus (EAM) in myocardial ischemia and to
      explore its underlying mechanisms in ROS-mediated signaling cascade in vivo and
      in vitro. MATERIALS AND METHODS: The saponins in EAM were analyzed using HPLC.
      The tests for the cardioprotective effects of EAM and its mechanisms were
      performed in vivo and in vitro. In vivo, the rat model of persistent myocardial
      ischemia was produced by occlusion of the left anterior descending (LAD) coronary
      artery. In vitro, the cardiomyocyte model of oxidative stress was mimicked by the
      direct free radical donor, H2O2. RESULTS: In vivo, the increased myocardial
      infarct size and the increased serum levels of lactate dehydrogenase (LDH),
      creatine kinase isoform MB (CK-MB), and cardiac troponin (cTnI) were
      significantly decreased by pre-treatment with EAM. Moreover, cardiac function, as
      assessed by+/-dP/dt, left ventricular developed pressure (LVDP), and left
      ventricular end-diastolic pressure (LVEDP), was dramatically improved. An
      oxidative stress biomarker, malondialdehyde (MDA), was reduced, and the
      antioxidant enzyme superoxide dismutase (SOD) was induced. In vitro, H2O2
      triggered myocardial cell death and cytoplasm Ca(2+) overload were blocked by
      treatment with EAM. Furthermore, the KATP channel blocker (5-HD, glibenclamide)
      blocked the anti-apoptotic protective effect of EAM on cardiomyocytes injured by
      H2O2. CONCLUSIONS: The cardioprotection of EAM was manifested as a protection of
      tissue structure and as a decrease in serum markers of ischemic injury. The
      mechanisms underlying the EAM-mediated protective effects may involve improving
      cardiac function, attenuating the oxidative injury via a decrease in MDA, a
      maintenance in SOD, and a reduction in free radical-induced myocardial cell
      injury. Additionally, EAM enhanced the myocardial cell viability via arresting
      the influx of Ca(2+) to block cell death and opening mitochondrial KATP channels
      to reduce cell apoptosis.

PMID- 23968863
TI  - Identification of intermediate risk breast cancer patients with 1-3 positive
      lymph nodes and excellent survival after tamoxifen as only systemic adjuvant
      therapy by use of markers of proliferation and apoptosis.
AB  - BACKGROUND: According to current guidelines, patients with primary breast cancer
      and 1-3 lymph node metastases will in general be offered adjuvant chemotherapy.
      AIM: Our objective was to investigate the relationship between markers of
      proliferation and apoptosis with survival for patients subjected to adjuvant
      tamoxifen solely. MATERIAL AND METHODS: Tumour cytosol samples from 409
      consecutive patients with operable oestrogen receptor positive BC, stage I-III
      and treated with tamoxifen for 2 or 5 years were assessed for levels of caspase
      cleaved cytokeratin-18 (ccCK18), an indicator of apoptosis, by use of an ELISA
      assay. Data on S-phase fraction (SPF) were available for 370 patients. Survival
      analyses were performed according to levels of ccCK18 and SPF separately, as well
      as combined. RESULTS: A wide range of ccCK18 protein levels was found, median
      9.97, range 0.0-87.3 pg/MUgDNA. Increasing SPFs were significantly associated
      with a lower distant recurrence-free survival (DRFS) (p = 0.025) and breast
      cancer survival (BCS) (p = 0.046). In the group with low SPF (below mean), low
      amounts of ccCK/18 correlated with a shorter DRFS (p = 0.0028) and BCS (p =
      0.0027). A Proliferation Index (PI); a quotient of ccCK18/SPF was constructed.
      Low PI (high ccCK18/SPF ratios) were significantly correlated with an improved
      survival both when analysed as continuous variables; DRFS (p = 0.021), BCS (p =
      0.038) and when divided into quartiles; DRFS (p < 0.001) and BCS (p = 0.0012). A
      similar correlation was found in patients with 1-3 lymph node metastases; DRFS (p
      = 0.089) and BCS (p = 0.019). A Cox's proportional hazard model including age,
      tumour size, lymph node status, PgR and ccCK18/SPF was used for multivariate
      analysis. High ccCK18/SPF ratios correlated with improved survival; DRFS (HR =
      0.47 (0.22-0.98), p = 0.043), and BCS (HR = 0.39 (0.16-1.00), p = 0.049),
      respectively. CONCLUSION: By use of a proliferation index based on markers of
      proliferation and apoptosis, a group of patients with 1-3 lymph node metastases
      with good outcome following adjuvant tamoxifen was identified; this group could
      possibly be spared adjuvant chemotherapy.

PMID- 23968864
TI  - Angiogenic factors in relation to clinical effect in a phase II trial of weekly
      paclitaxel.
AB  - BACKGROUND: Several anticancer agents including paclitaxel have an inhibitory
      effect on angiogenesis. AIMS: To compare the overall response rate and time to
      progression with changes in circulating angiogenic factors during palliative
      treatment with weekly paclitaxel. MATERIAL AND METHODS: Patients with metastatic
      BC, ECOG 0-2, received weekly paclitaxel, concomitant with trastuzumab if HER2+
      BC (n = 7). Circulating vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (bFGF) were determined at base-line and before start of
      new course. RESULTS: Fifty-five of 63 included patients were evaluable. The
      overall response rate including stable disease >=24 weeks (CR + PD + SD) was
      obtained in 25 of the evaluable patients (45%). The median time to progression
      (TTP) was 5.3 months and overall survival (OS) 16.7 months. Patients with triple
      negative breast cancer (TNBC) showed a trend towards higher base-line VEGF
      compared with hormone receptor positive or HER2+ tumours and had shorter TTP.
      Significant differences in VEGF and bFGF levels at 12 weeks were found between
      patients with longer versus shorter TTP (VEGF: p = 0.046, bFGF: p = 0.005) and
      between patients gaining versus lacking clinical benefit (VEGF: p = 0.05, bFGF: p
      = 0.02). CONCLUSIONS: The clinical utility of circulating VEGF may be a useful
      tool for monitoring treatment efficacy.

PMID- 23968865
TI  - The first two lines of chemotherapy for anthracycline-naive metastatic breast
      cancer: a comparative study of the efficacy of anthracyclines and non
      anthracyclines.
AB  - For anthracycline-naive metastatic breast cancer (AN-MBC), early anthracycline
      treatment is a common practice. However, with the availability of newer
      chemotherapies, comparative studies on the efficacy of anthracyclines and non
      anthracyclines as early treatments for AN-MBC are lacking. We collected
      retrospective clinicopathological data from 253 AN-MBC patients treated at
      National Taiwan University Hospital between 2001 and 2006. Patients were
      categorised into anthracycline or non-anthracycline groups according to their
      regimens in the first two lines of chemotherapy. The overall survival (OS, 33.3
      vs. 34.2 months, p = 0.179), time to treatment failure of the first two lines of
      chemotherapy drugs (13.3 vs. 12.7 months, p = 0.104) and best composite response
      rate (59.5% vs. 61.1%, p = 0.81) were not significantly different between the two
      groups. Multivariate analysis showed that early anthracycline treatment was not a
      significant prognostic factor of OS (p = 0.052). Thus, the results of this study
      show that anthracyclines may not be necessary as an early treatment option for AN
      MBC. 

PMID- 23968866
TI  - Prognostic value of insulin-like growth factor 1 and insulin-like growth factor
      binding protein 3 blood levels in breast cancer.
AB  - High circulating insulin-like growth factor 1 (IGF-1) levels are firmly
      established as a risk factor for developing breast cancer, especially estrogen
      positive tumors. The effect of circulating IGF-1 on prognosis once a tumor is
      established is unknown. The authors explored the effect of IGF-1 blood levels and
      of it's main binding protein, IGFBP-3, on overall survival and occurrence of
      second primary breast tumors in breast cancer patients, as well as reproductive
      and lifestyle factors that could modify this risk. Patients were accrued from six
      hospitals in the Netherlands between 1998 and 2003. Total IGF-1 and IGFBP-3 were
      measured in 582 plasma samples. No significant association between IGF-1 and
      IGFBP-3 plasma levels and overall survival was found. However, in a multivariate
      Cox regression model including standard prognostic variables high IGF-1 levels
      were related to worse overall survival in patients receiving endocrine therapy
      (HR = 1.37, 95% CI: 1.11, 1.69, P 0.004). These data at least indicate that
      higher IGF-1 levels, and as a consequence most likely IGF-1-induced signaling,
      are related to a less favorable overall survival in breast cancer patients
      treated with endocrine therapy. Interventions aimed at reducing circulating
      levels of IGF-1 in hormone receptor positive breast cancer may improve survival. 

PMID- 23968867
TI  - Effects of sustained swimming on the red and white muscle transcriptome of
      rainbow trout (Oncorhynchus mykiss) fed a carbohydrate-rich diet.
AB  - Training at sustainable swimming speeds can produce changes in fish skeletal
      muscle that are important for aquaculture due to their growth-potentiating
      effects. Such changes may be even more relevant when fish are fed diets
      containing an increasing proportion of carbohydrates as an energy source. We
      evaluated the effects of moderate-intensity sustained swimming on the
      transcriptomic response of red and white muscle in rainbow trout fed a
      carbohydrate-rich diet using microarray and qPCR. Analysis of the red and white
      muscle transcriptome in resting or swimming (1.3 body lengths/s) fish for 30days
      revealed significant changes in the expression of a large number of genes (395
      and 597, respectively), with a total of 218 differentially expressed genes (DEGs)
      common for both muscles. A large number of the genes involved in glucose use and
      energy generation, contraction, development, synthesis and catabolism of proteins
      were up-regulated in red and white muscle. Additionally, DEGs in both muscles
      were involved in processes of defense response and apoptosis. Skeletal muscle
      contraction activates a transcriptional program required for the successful
      adaptation of both muscles to the changing demands imposed by swimming
      conditions. Future studies should further clarify the mechanisms involved in the
      adaptation of both tissues to exercise and assess possible benefits of such
      conditions for cultured fish. 

PMID- 23968868
TI  - Dynamic processes of indigenous microorganisms from a low-temperature petroleum
      reservoir during nutrient stimulation.
AB  - Compared to medium-high temperature petroleum reservoirs (30 degrees C-73 degrees
      C), little is known about microbial regulation by nutrients in low-temperature
      reservoirs. In this study, we report the performance (oil emulsification and
      biogas production) and community structure of indigenous microorganisms from a
      low-temperature (22.6 degrees C) petroleum reservoir during nutrient stimulation.
      Culture-dependent approaches indicated that the number of hydrocarbon-oxidizing
      bacteria (HOB), nitrate-reducing bacteria (NRB) and methane-producing bacteria
      (MPB) increased by between 10- and 1000-fold, while sulfate-reducing bacteria
      (SRB) were observed at low levels during stimulation. Phylogenetic analysis of
      the 16S rRNA gene indicated that Pseudomonas, Ochrobactrum, Acinetobacter,
      Halomonas and Marinobacter, which have the capability to produce surfactants,
      were selectively enriched. Methanoculleus, Methanosaeta, Methanocorpusculum and
      Methanocalculus showed the largest increase in relative abundance among archaea.
      Micro-emulsion formed with an average oil droplet diameter of 14.3 MUm (ranging
      between 4.1 MUm and 84.2 MUm) during stimulation. Gas chromatographic analysis of
      gas production (186 mL gas/200 mL medium) showed the levels of CO2 and CH4
      increased 8.97% and 6.21%, respectively. Similar to medium-high temperature
      reservoirs, HOB, NRB, SRB and MPB were ubiquitous in the low-temperature
      reservoir, and oil emulsification and gas production were the main phenomena
      observed during stimulation. Oil emulsification required a longer duration of
      time to occur in the low-temperature reservoir. 

PMID- 23968869
TI  - Different-batch metabolome analysis of Saccharomyces cerevisiae based on gas
      chromatography/mass spectrometry.
AB  - Each experimental step in metabolomics based on mass spectrometry for
      microorganisms, such as cultivation, sampling, extraction of metabolites,
      analysis, and data processing includes different systematic errors. Even if the
      same protocol is used, it is difficult to compare the data from different
      cultivation days or different analysis days. To obtain reliable quantitative
      data, it is necessary to develop an analytical workflow that can reduce errors
      from different batch of cultivation and analysis days. We compared metabolomics
      methods for Saccharomyces cerevisiae in terms of reproducibility to optimize the
      analytical workflow, particularly quenching and data processing. Our data also
      showed that reproducible data could be obtained with high signal to noise ratio.
      Therefore, we optimized a time segmented selective ion monitoring (SIM) method
      for high sensitive analysis with low-risk of false positives. The optimized
      workflow was applied to metabolome analysis of single transcription factor
      deletion mutants. As a result, we obtained clusters that were independent of
      cultivation day and analysis day but were strain-dependent. This study can help
      to implement large-scale or long-term studies, in which samples are divided among
      several laboratories because of the high number of samples. 

PMID- 23968870
TI  - Risk scores for predicting mortality after surgical ventricular reconstruction
      for ischemic cardiomyopathy: results of a Japanese multicenter study.
AB  - OBJECTIVES: Surgical ventricular reconstruction has been believed to be
      beneficial for those with ischemic cardiomyopathy. However, the effectiveness of
      surgical ventricular reconstruction was not proved by a large-scale trial, and no
      report has clearly demonstrated the exact indications and limitations of surgical
      ventricular reconstruction. The purpose of this study was to elucidate predictive
      factors of mortality after surgical ventricular reconstruction and to develop a
      prognostic model by calculating risk scores. METHODS: The study subjects were 596
      patients who underwent surgical ventricular reconstruction for chronic ischemic
      heart failure in 11 Japanese cardiovascular hospitals between 2000 and 2010.
      Potential predictors of postoperative mortality were assessed using the Cox
      proportional hazards model, and a risk score was calculated. RESULTS: Forty-one
      patients died before discharge, and 81 patients died during a mean follow-up time
      of 2.9 years. Four independent predictors of mortality were identified: age,
      Interagency Registry for Mechanically Assisted Circulatory Support profile, left
      ventricular ejection fraction, and severity of mitral regurgitation. Each
      variable was assigned a number of points proportional to its regression
      coefficient. A risk score was calculated using the point scores for each patient,
      and 3 risk groups were developed: a low-risk group (0-4 points), an intermediate
      risk group (5-6 points), and a high-risk group (7-12 points). Their 3-year
      survivals were 93%, 81%, and 44%, respectively (log-rank P < .001). Harrell's C
      index of the predictive model was 0.69. CONCLUSIONS: A simple prognostic model
      was developed to predict mortality after surgical ventricular reconstruction. It
      can be useful in clinical practice to select treatment options for ischemic heart
      failure.

PMID- 23968872
TI  - MicroRNA-30b is a multifunctional regulator of aortic valve interstitial cells.
AB  - OBJECTIVE: Calcific aortic valve disease is an active process involving a wide
      range of pathologic changes. Valve interstitial cells are the most prevalent
      cells in the heart valve and maintain normal valve structure and function.
      MicroRNAs (miRNAs) are essential posttranscriptional modulators of gene
      expression, and miRNA-30b is a known repressor of bone morphogenetic protein 2
      mediated osteogenesis. We hypothesized that miRNA-30b is a multifunctional
      regulator of aortic valve interstitial cells during calcification. METHODS: To
      determine the role of miRNA-30b in calcific aortic valve disease, we evaluated
      miRNA expression in human calcific aortic valve leaflets obtained
      intraoperatively. Furthermore, human valve interstitial cells were evaluated with
      regard to miRNA-30b expression and osteogenesis by quantitative real-time
      polymerase chain reaction, Western blotting, flow cytometry, and alkaline
      phosphatase assays. RESULTS: In this study, we demonstrated that miRNA-30b
      attenuates bone morphogenetic protein 2-induced osteoblast differentiation by
      targeting Runx2, Smad1, and caspase-3. Transfection of a mimic of miRNA-30b led
      to decreases in alkaline phosphatase activity and expressions of Runx2, Smad1,
      and caspase-3. Furthermore, dual luciferase reporter assays confirmed that Runx2,
      Smad1, and caspase-3 are direct targets of miRNA-30b. CONCLUSIONS: We
      demonstrated a remarkable role of miRNA-30b in calcific aortic valve disease as a
      regulator of human aortic valvular calcification and apoptosis through direct
      targeting of Runx2, Smad1, and caspase-3. Targeting of miRNA-30b could serve as a
      novel therapeutic strategy to limit progressive calcification in aortic stenosis.

PMID- 23968871
TI  - Invasive mechanical ventilation in patients with fibrosing interstitial
      pneumonia.
AB  - OBJECTIVE: The prognosis of patients with idiopathic pulmonary fibrosis or
      fibrosing idiopathic nonspecific interstitial pneumonia undergoing invasive
      mechanical ventilation (MV) for acute respiratory failure is known to be poor.
      The issue of life support in these patients needs to be reconsidered in light of
      changes during the past decade in ventilator settings and in the management of
      acute exacerbation. We therefore aimed to reassess the prognosis of such
      patients. METHODS: We retrospectively assessed the outcomes of all medical
      patients with idiopathic pulmonary fibrosis or fibrosing idiopathic nonspecific
      interstitial pneumonia who required invasive MV in 3 university hospitals in the
      Paris area from January 2002 to April 2009. RESULTS: In total, 27 patients (mean
      age, 66 +/- 12.8 years) required invasive MV in the intensive care unit: 8 (30%)
      were successfully weaned from MV, and 6 and 4 were discharged from the intensive
      care unit and the hospital, respectively. Survivals for patients who did not
      undergo lung transplant were 22%, 3.7%, and 3.7%, at 30 days, 6 months, and 12
      months, respectively. CONCLUSIONS: We confirm that use of invasive MV for acute
      respiratory failure in patients with idiopathic pulmonary fibrosis or fibrosing
      idiopathic nonspecific interstitial pneumonia is associated with a high
      mortality; however, a subset of patients may be discharged alive from the
      intensive care unit and hospital, providing an opportunity to consider lung
      transplant in case of eligibility. Our results suggest that invasive MV should
      not be systematically denied to these patients but discussed on a case-by-case
      basis.

PMID- 23968873
TI  - Simultaneous relief of acute visceral and limb ischemia in complicated type B
      aortic dissection by axillobifemoral bypass.

PMID- 23968874
TI  - A surge of MDR and XDR tuberculosis in France among patients born in the Former
      Soviet Union.
AB  - A marked increase in the number of multidrug-resistant (MDR) tuberculosis (TB)
      cases entirely related to patients born in the Former Soviet Union was observed
      in France in the last two years. Very few cases were clustered, suggesting it is
      a consequence of recent immigration of patients already infected in their country
      of origin. This major increase challenges the existing structures for management
      of MDR and extensively drug-resistant TB (XDR-TB).

PMID- 23968875
TI  - Increased incidence of invasive group A streptococcal disease in Ireland, 2012 to
      2013.
AB  - Invasive group A streptococcal (iGAS) infections have been notifiable in Ireland
      since 2004. Incidence rates (2004-2011) have ranged from 0.8 to 1.65 per 100,000.
      In 2012, the iGAS rate rose to 2.66 per 100,000 and was associated with a high
      proportion of emm1 isolates. A further increase in January to June 2013 has been
      associated with increased prevalence of emm3. Public health departments and
      clinicians have been alerted to this increase.

PMID- 23968876
TI  - Increase in gonorrhoea among very young adolescents, Catalonia, Spain, January
      2012 to June 2013.
AB  - Between January 2012 and June 2013, 27 sexually transmitted infections were
      reported in adolescents aged 13-15 years in Catalonia, Spain. In the first half
      of 2013, there were nine cases of gonorrhoea, while in the same period of 2012,
      there was one. In June 2013, two gonorrhoea cases aged 13-14 years, linked to a
      common source through a social network, were reported. The public health response
      should be adapted to this vulnerable population.

PMID- 23968877
TI  - Mumps epidemiology in Germany 2007-11.
AB  - In Germany, mumps has been notifiable until 2013 only in the five Eastern federal
      states (EFS) of former East Germany. Due to different immunisation policies until
      1990 and varying vaccination coverages thereafter, mumps incidences cannot be
      extrapolated to the 11 Western federal states (WFS). We studied mumps-related
      International Classification of Diseases (ICD-10) code diagnoses claimed through
      statutory health insurances between 2007 and 2011 to estimate countrywide mumps
      incidences in the outpatient sector, and compared them with case numbers from
      ambulatory notification data. Overall, 32,330 outpatient mumps cases were
      claimed. Annual incidence ranged between 9.3/100,000 and 11.8/100,000 and showed
      a significant decreasing trend. Compared with EFS, mumps incidence in WFS was
      higher and indicated a shift towards older age groups. Notified outpatient case
      numbers in EFS were 13-fold lower and from voluntary surveillance during an
      outbreak in the WFS Bavaria 8-fold lower than from insurance data (n=316 versus
      n=4,217 and n=238 versus 1,995, respectively). Of all notified cases with
      available information, 75.4% (EFS) and 57.6% (Bavaria) were unvaccinated; 6.8%
      (EFS) and 19.3% (Bavaria) required hospitalisation. In Germany, mumps is still
      endemic despite decades of vaccination, with considerable underreporting in the
      established notification systems.

PMID- 23968878
TI  - Journal of Open Public Health Data launched.

PMID- 23968879
TI  - WHO launches World health report 2013.

PMID- 23968880
TI  - Reduction of adolescent alcohol use through family-school intervention: a
      randomized trial.
AB  - PURPOSE: Two-year longitudinal follow-up data evaluated the behavioral impact of
      Resilient Families, a universal intervention that aimed to prevent early
      initiation and frequent and heavy adolescent alcohol use in secondary schools in
      Melbourne, Australia. METHODS: Of 24 secondary schools (62% of those approached),
      12 were randomly assigned to intervention and 12 as controls. Intervention
      students received a social relationship curriculum; their parents received parent
      education handbooks and invitations to parent education events outlining
      strategies to encourage healthy adolescent development and reduce adolescent
      alcohol misuse. At Wave 1 (2004), students were in Year 7 secondary school (mean
      age, 12.3 years). Data were imputed for students completing at least two of three
      annual surveys (N = 2,354). Wave 3 (2006; mean, 14.5 years) main outcome measures
      for alcohol use were "any," "frequent" (at least monthly), and "heavy" (five or
      more drinks in a session at least once in the prior fortnight). Multivariate
      logistic regression assessed intervention exposure effects, adjusting for school
      classroom clustering and baseline measures. RESULTS: Relative to controls,
      intervention students showed significant reductions in any lifetime use (adjusted
      odds ratio [AOR], .78; 95% confidence interval [CI], .62-.97), and reduced
      progression to frequent (AOR, .69; CI, .56-.86) and heavy use (AOR, .75; CI, .60
      .94). CONCLUSIONS: Randomized assignment to Resilient Families was associated
      with a significant reduction in adolescent alcohol use among families
      volunteering for the evaluation. Family-school-based interventions appear
      promising as a strategy to contribute to population reductions in currently high
      rates of adolescent alcohol misuse.

PMID- 23968881
TI  - Screening practices for identifying type 2 diabetes in adolescents.
AB  - OBJECTIVE: To characterize pediatrician and family physician (FP) screening
      practices for type 2 diabetes among adolescents and to examine the impact of the
      2010 American Diabetes Association (ADA) guidelines, recommending use of
      Hemoglobin A1c (HbA1c). METHODS: We conducted a cross-sectional mail survey of a
      random sample of 1,400 U.S. pediatricians and FPs and we received 604 eligible
      responses. Our main outcome measure was the types of tests ordered by physicians,
      particularly HbA1c, when presented with a hypothetical scenario. RESULTS: The
      overall response rate was 52% (57% for pediatricians and 48% for FPs). Fasting
      glucose and HbA1c were the most commonly ordered tests. Overall, at least 58% of
      physicians ordered HbA1c; 35% ordered HbA1c in conjunction with fasting tests;
      and 22% ordered HbA1c alone or with nonfasting tests. Only 38% of providers were
      aware of the new ADA recommended HbA1c screening guidelines. However, a majority
      (67%) said they would change their screening practices. In the context of the
      guidelines, 84% of physicians would now order HbA1c. Furthermore, there was a
      large increase in the proportion of physicians who would shift to using HbA1c
      only or with other nonfasting tests. CONCLUSIONS: When screening adolescents for
      type 2 diabetes, providers are more likely to order HbA1c and order fewer fasting
      tests in response to the new ADA guidelines. HbA1c has lower sensitivity and
      higher costs than other testing modalities in children, therefore increasing
      uptake of this test (HbA1c) in children may have implications for both detection
      rates and healthcare costs.

PMID- 23968883
TI  - Human TRPV5 and TRPV6: key players in cadmium and zinc toxicity.
AB  - TRPV5 and TRPV6 are two major calcium transport pathways in the human body
      maintaining calcium homeostasis. TRPV5 is mainly expressed in the distal
      convoluted and connecting tubule where it is the major, regulated pathway for
      calcium reabsorption. TRPV6 serves as an important calcium entry pathway in the
      duodenum and the placenta. Previously, we showed that human TRPV6 (hTRPV6)
      transports several heavy metals. In this study we tested whether human TRPV5
      (hTRPV5) also transports cadmium and zinc, and whether hTRPV5 together with
      hTRPV6 are involved in cadmium and zinc toxicity. The hTRPV5 mRNA and protein
      were expressed in HEK293 cells transiently transfected with pTagRFP-C1-hTRPV5.
      The overexpression of the hTRPV5 protein at the plasma membrane was revealed by
      cell surface biotinylation and immunofluorescence techniques. We observed that
      both cadmium and zinc permeate hTRPV5 in ion imaging experiments using Fura-2 or
      Newport Green DCF. Our results were further confirmed using whole-cell patch
      clamp technique. Transient overexpression of hTRPV5 or hTRPV6 sensitized cells to
      cadmium and zinc. Toxicity curves of cadmium and zinc were also shifted in hTRPV6
      expressing HEK293 cells clones. Our results suggest that TRPV5 and TRPV6 are
      crucial gates controlling cadmium and zinc levels in the human body especially
      under low calcium dietary conditions, when these channels are maximally
      upregulated. 

PMID- 23968882
TI  - Characterization of store-operated Ca2+ channels in pancreatic duct epithelia.
AB  - Store-operated Ca2+ channels (SOCs) are activated by depletion of intracellular
      Ca2+ stores following agonist-mediated Ca2+ release. Previously we demonstrated
      that Ca2+ influx through SOCs elicits exocytosis efficiently in pancreatic duct
      epithelial cells (PDEC). Here we describe the biophysical, pharmacological, and
      molecular properties of the duct epithelial SOCs using Ca2+ imaging, whole-cell
      patch-clamp, and molecular biology. In PDEC, agonists of purinergic, muscarinic,
      and adrenergic receptors coupled to phospholipase C activated SOC-mediated Ca2+
      influx as Ca2+ was released from intracellular stores. Direct measurement of
      [Ca2+] in the ER showed that SOCs greatly slowed depletion of the ER. Using IP3
      or thapsigargin in the patch pipette elicited inwardly rectifying SOC currents.
      The currents increased ~8-fold after removal of extracellular divalent cations,
      suggesting competitive permeation between mono- and divalent cations. The current
      was completely blocked by high doses of La3+ and 2-aminoethoxydiphenyl borate (2
      APB) but only partially depressed by SKF-96365. In polarized PDEC, SOCs were
      localized specifically to the basolateral membrane. RT-PCR screening revealed the
      expression of both STIM and Orai proteins for the formation of SOCs in PDEC. By
      expression of fluorescent STIM1 and Orai1 proteins in PDEC, we confirmed that
      colocalization of the two proteins increases after store depletion. In
      conclusion, basolateral Ca2+ entry through SOCs fills internal Ca2+ stores
      depleted by external stimuli and will facilitate cellular processes dependent on
      cytoplasmic Ca2+ such as salt and mucin secretion from the exocrine pancreatic
      ducts.

PMID- 23968884
TI  - Dynamics of Akt activation during mouse embryo development: distinct subcellular
      patterns distinguish proliferating versus differentiating cells.
AB  - Akt is a highly conserved serine-threonine protein kinase which has been
      implicated in a wide variety of cellular functions, from the regulation of growth
      and metabolism, to activation of pro-survival pathways and cell proliferation,
      and promotion of differentiation in specific cell types. However, very little is
      known about the spatial and temporal pattern of Akt activity within cells and
      whether this pattern changes as cells enter and proceed in their differentiation
      programs. To address this issue we profiled Akt activation in E8.5-E13.5 mouse
      embryos and in C2C12 cells. We used a commercial antibody against Akt,
      phosphorylated on one of its activating residues, Thr-308, and performed high
      resolution confocal imaging of the immunofluorescence in labeled embryos. We
      observe strong Akt activity during mitosis in the dermomyotome, the
      neuroepithelium and some mesenchymal cells. This burst of activity fills the
      whole cell except for heterochromatin-positive areas in the nucleus. A surge in
      activity during mitosis is also observed in subconfluent C2C12 cells. Later on in
      the differentiation programs of skeletal muscle and neural cells, derivatives of
      the dermomyotome and neuroepithelium, respectively, we find robust, sustained Akt
      activity in the cytoplasm, but not in the nucleus. Concomitantly with skeletal
      muscle differentiation, Akt activity becomes concentrated in the sarcomeric Z
      disks whereas developing neurons maintain a uniform cytoplasmic pattern of
      activated Akt. Our findings reveal unprecedented cellular and subcellular details
      of Akt activity during mouse embryo development, which is spatially and
      temporally consistent with proposed functions for Akt in mitosis and myogenic and
      neural differentiation and/or survival. Our results thus demonstrate a
      subcellular change in the pattern of Akt activation when skeletal muscle and
      neural progenitor cells cease dividing and progress in their differentiation
      programs. 

PMID- 23968885
TI  - Identification of cross-clade CTL epitopes in HIV-1 clade A/E-infected
      individuals by using the clade B overlapping peptides.
AB  - Identification of cross-clade T cell epitopes is one of key factors for the
      development of a widely applicable AIDS vaccine. We here investigated cross-clade
      CD8(+) T cell responses between clade B and A/E viruses in chronically HIV-1
      clade A/E-infected Japanese individuals. CD8(+) T cell responses to 11-mer
      overlapping peptides derived from Nef, Gag, and Pol clade B consensus sequences
      were at a similar level to those to the same peptides found in clade B-infected
      individuals. Fifteen cross-clade CTL epitopes were identified from 13 regions
      where the frequency of responders was high in the clade A/E-infected individuals.
      The sequences of 6 epitopes were conserved between the clade B and clade A/E
      viruses whereas 9 epitopes had different amino acid sequences between the 2
      viruses. CD8(+) T cells specific for the 6 conserved epitopes recognized cells
      infected with the clade A/E virus, whereas those for 8 diverse epitopes
      recognized both the clade A/E virus-infected and clade B-infected cells. All of
      the cross-clade CD8(+) T cells specific for conserved and diverse epitopes were
      detected in chronically HIV-1 clade A/E-infected individuals. These results show
      that in addition to conserved regions polymorphic ones across the clades can be
      targets for cross-clade CTLs. 

PMID- 23968886
TI  - Canadian Headache Society Guideline: acute drug therapy for migraine headache.
AB  - OBJECTIVES: The primary objective of this guideline is to assist the practitioner
      in choosing an appropriate acute medication for an individual with migraine,
      based on current evidence in the medical literature and expert consensus. It is
      focused on patients with episodic migraine ( headache on <= 14 days a month).
      METHODS: A detailed search strategy was used to find a relevant meta-analyses,
      systematic reviews and randomized double-blind controlled trials. Recommendations
      were graded with the Grading of Recommendations Assessment, Development and
      Evaluation (GRADE) Working Group, using a consensus group. In addition, a general
      literature review and expert consensus were used for aspects of acute therapy for
      which randomized controlled trials were not available. RESULTS: Twelve acute
      medications received a strong recommendation for use in acute migraine therapy
      (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan,
      zomitriptan, ASA, ibuprofen, naproxen sodium, diclofenac potassium, and
      acetaminophen). Four received a weak recommendation for use (dihydroergotamine,
      ergotamine, codeine-containing combination analgesics, and tramadol- containing
      medications). Three of these were NOT recommended for routine use (ergotamine and
      codeine- and tramadol- containing medications). Strong recommendations were made
      to avoid use of butorphanol and butalbital- containing medications.
      Metoclopramide and domperidone were strongly recommended for use when necessary.
      Our analysis also resulted in the formulation of eight general acute migraine
      management strategies. These were grouped into: 1) two mild-moderate attack
      strategies, 2) two moderate-severe attack or NSAID failure strategies, 3) three
      refractory migraine strategies, and 4) a vasoconstrictor unresponsive
      contraindicated strategy. Additional were developed for menstrual migraine during
      pregnancy, and migraine during lactation. CONCLUSION: This guideline provides
      evidence-based advice on acute pharmacological migraine therapy, and should be
      helpful to both health professionals and patients, The available medications have
      been organized into a series of strategies based on patient clinical features.
      These strategies may help practitioners make appropriate acute medication choices
      for patients with migraine.

PMID- 23968887
TI  - CD141+ myeloid dendritic cells are enriched in healthy human liver.
AB  - BACKGROUND & AIMS: Extensive populations of liver immune cells detect and respond
      to homeostatic perturbation caused by damage, infection or malignancy. Dendritic
      cells (DCs) are central to these activities, governing the balance between
      tolerance and immunity. Most of our knowledge about human liver DCs is derived
      from studies on peritumoral tissue. Little is known about the phenotype and
      function of DCs, in particular the recently described CD141(+) subset, in healthy
      human liver and how this profile is altered in liver disease. METHODS: During
      liver transplantation, healthy donor and diseased explant livers were perfused
      and hepatic mononuclear cells isolated. Dendritic cell subset frequency and
      phenotype were characterised in liver perfusates by flow cytometry and the
      function of CD141(+) DCs was evaluated by mixed lymphocyte reactions (MLRs) and
      measuring cytokine secretion. RESULTS: Almost one third of liver CD11c(+) myeloid
      DCs (mDCs) expressed CD141 compared to <5% of circulating mDCs. Hepatic CD141(+)
      DCs demonstrated pro-inflammatory function in allogeneic MLRs, inducing T cell
      production of interferon gamma (IFN-gamma) and interleukin (IL)-17. While
      CD123(+) plasmacytoid DCs (pDCs) and CD1c(+) mDCs were expanded in diseased liver
      perfusates, CD141(+) DCs were significantly depleted. Despite their depletion,
      CD141(+) DCs from explant livers produced markedly increased poly(I:C)-induced
      IFN lambda (IFN-lambda) compared with donor DCs. CONCLUSIONS: Accumulation of
      CD141(+) DCs in healthy liver, which are significantly depleted in liver disease,
      suggests differential involvement of mDC subsets in liver immunity.

PMID- 23968888
TI  - Resistin and visfatin in steatotic and non-steatotic livers in the setting of
      partial hepatectomy under ischemia-reperfusion.
AB  - BACKGROUND & AIMS: This study examined whether the regulation of resistin and
      visfatin could reduce damage and improve regeneration in both steatotic and non
      steatotic livers undergoing partial hepatectomy under ischemia-reperfusion, a
      procedure commonly applied in clinical practice to reduce bleeding. METHODS:
      Resistin and visfatin were pharmacologically modulated in lean and obese animals
      undergoing partial hepatectomy under ischemia-reperfusion. RESULTS: No evident
      role for these adipocytokines was observed in non-steatotic livers. However,
      obese animals undergoing liver surgery showed increased resistin in liver and
      plasma, without changes in adipose tissue, together with visfatin downregulation
      in liver and increment in plasma and adipose tissue. Endogenous resistin
      maintains low levels of visfatin in the liver by blocking its hepatic uptake from
      the circulation, thus regulating the visfatin detrimental effects on hepatic
      damage and regenerative failure. Indeed, the administration of anti-resistin
      antibodies increased hepatic accumulation of adipocyte-derived visfatin,
      exacerbating damage and regenerative failure. Interestingly, treatment with anti
      visfatin antibodies protected steatotic livers, and similar results were obtained
      with the concomitant inhibition of resistin and visfatin. Thus, when visfatin was
      inhibited, the injurious effects of anti-resistin antibodies disappeared. Herein
      we show that upregulation of visfatin increased NAD levels in the remnant
      steatotic liver, whereas visfatin inhibition decreased them. These later
      observations suggest that visfatin may favour synthesis of NAD instead of DNA and
      induces alterations in amino acid metabolism-urea cycle and NO production,
      overall negatively affecting liver viability. CONCLUSIONS: Our results indicate
      the clinical potential of visfatin blocking-based therapies in steatotic livers
      undergoing partial hepatectomy with ischemia-reperfusion.

PMID- 23968889
TI  - Identification of gyrB and rpoB gene mutations and differentially expressed
      proteins between a novobiocin-resistant Aeromonas hydrophila catfish vaccine
      strain and its virulent parent strain.
AB  - A total of 10 and 13 missense mutations were found in the deduced gyrB and rpoB
      proteins, respectively, between avirulent AH11NOVO vaccine strain and its
      virulent parent strain AH11P. SDS-PAGE revealed that six proteins bands were
      significantly over-expressed in AH11NOVO whereas five bands were significantly
      over-expressed in AH11P. Mass spectrometry identified seven proteins from the
      over-expressed AH11NOVO gel bands and five proteins from the over-expressed AH11P
      gel bands. QPCR confirmed that all 12 genes corresponding to the proteins
      identified by mass spectrometry were significantly over-expressed in AH11NOVO or
      AH11P. When AH11NOVO proteins were subjected to Western blot analysis, 13 protein
      bands exhibited significantly stronger reactivity with hyper-immune catfish sera.
      Fifteen proteins were identified from immunogenic protein bands, including six
      (formate acetyltransferase, chaperone htpG, transketolase, ATP synthase subunit
      alpha, asparagine-tRNA ligase, and serine hydroxymethyltransferase) that were
      over-expressed in AH11NOVO proteins and three (elongation factor G, class II
      fructose-bisphosphate aldolase, and a putative uncharacterized 23 kDa protein)
      that were over-expressed in AH11P. In addition, the following six proteins were
      also identified from the immunogenic protein bands: pyruvate dehydrogenase E1
      component, ATP synthase subunit beta, ribose-phosphate pyrophosphokinase,
      glyceraldehyde-3-phosphate dehydrogenase, 50S ribosomal L10, and 50S ribosomal
      L15. Our results might provide insights on how to develop novel efficacious
      vaccine against Aeromonas hydrophila infection.

PMID- 23968891
TI  - Growth and residual stresses of arterial walls.
AB  - Growth, residual stresses and mechanical responses of arterial walls under the
      inner pressure are investigated within the framework of a finite deformation
      hyper-elasticity theory. A biomechanical model for a two-layer thick-walled
      circular cylindrical tube is proposed to address the mechanical effects of finite
      volumetric growth and residual stresses of arterial walls. The active stress due
      to smooth muscle tone in the media and the dispersion of collagen fiber
      orientations in the adventitia are also considered. The fields of displacements
      and stress distributions of arterial walls with growth are solved analytically.
      Analysis of axial, radial and circumferential growth is considered and residual
      stress distributions of arterial walls in different cases of growth are compared.

PMID- 23968890
TI  - Pathogenesis of Venezuelan equine encephalitis.
AB  - Equine encephalids have high mortality rates and represent a significant zoonotic
      public health threat. Of these the most pathogenic viruses to equids are the
      alphaviruses in the family Togaviridae. The focus of this review Venezualen
      equine encephalitis virus (VEEV) has caused the most widespread and recent
      epidemic outbreaks of disease. Circulation in naturally occuring rodent-mosquito
      cycles, results in viral spread to both human and equine populations. However,
      equines develop a high titer viremia and can transmit the virus back to mosquito
      populations. As such, the early recognition and control of viral infection in
      equine populations is strongly associated with prevention of epidemic spread of
      the virus and limiting of disease incidence in human populations. This review
      will address identification and pathogenesis of VEEV in equids vaccination and
      treatment options, and current research for drug and vaccine development. 

PMID- 23968892
TI  - Psychological interventions for adolescent psychosis: a pilot controlled trial in
      routine care.
AB  - PURPOSE: Evidence for the recommendation to deliver Cognitive Behavioural Therapy
      (CBT) and Family Interventions (FI) to under-18s with psychosis derives from
      adult research, and no previous study has focused exclusively on an adolescent
      population. We evaluated adaptations of these therapies for adolescent inpatients
      with psychosis (CBTpA and FIpA), delivered as an adjunct to inpatient standard
      care (SC). SUBJECTS AND METHODS: Thirty adolescent inpatients with psychotic
      symptoms on admission were sequentially allocated to receive CBTpA+SC (n=10);
      FIpA+SC (n=10) or SC alone (n=10). Psychotic symptoms and functioning were
      measured at admission and discharge. RESULTS: Group comparisons did not reach
      conventional significance, but effect sizes in this pilot study showed a
      promising impact of CBTpA compared to SC alone, in reducing symptoms (ES: d=0.6),
      with smaller effect sizes for functioning (d=0.2) and for FIpA (symptoms, d=0.1
      and functioning, d=0.4). There was no advantage of either additional treatment in
      reducing length of stay, but self-report satisfaction ratings were higher for
      both psychological therapies. DISCUSSION AND CONCLUSIONS: The study is the first
      to focus on an exclusively adolescent population, using appropriately adapted
      therapy protocols. Findings suggest that the interventions are feasible,
      acceptable and helpful for adolescents with psychosis. Larger randomised
      controlled trials are now needed.

PMID- 23968893
TI  - Polymeric nanoparticles for optical sensing.
AB  - Nanotechnology is a powerful tool for use in diagnostic applications. For these
      purposes a variety of functional nanoparticles containing fluorescent labels,
      gold and quantum dots at their cores have been produced, with the aim of enhanced
      sensitivity and multiplexing capabilities. This work will review progress in the
      application of polymeric nanoparticles in optical diagnostics, both for in vitro
      and in vivo detection, together with a discussion of their biodistribution and
      biocompatibility. 

PMID- 23968894
TI  - A predictive model of longitudinal, patient-specific colonoscopy results.
AB  - We suggest a model framework, in which an individual patient's risk for colonic
      neoplasia varies based on findings from his previous colonoscopies, to predict
      longitudinal colonoscopy results. The neoplasia natural history model describes
      progression through four neoplasia development states with patient age. Multiple
      natural history model parameter sets are assumed to act concurrently on the colon
      and parameter set prevalence combinations, whose a priori likelihoods are a
      function of patient sex, provide a basis set for patient-level predictions. The
      novelty in this approach is that after a colonoscopy, both the parameter set
      combination likelihoods and their model predictions can adjust in a Bayesian
      manner based on the results and conditions of the colonoscopy. The adjustment of
      model predictions operationalizes the clinical knowledge that multiple or
      advanced neoplasia at baseline colonoscopy is an independent predictor of
      multiple or advanced neoplasia at follow-up colonoscopy--and vice versa for
      negative colonoscopies--and the adjustment of parameter set combination
      likelihoods accounts for the possibility that patients may have different
      neoplasia development rates. A model that accurately captures serial colonoscopy
      results could potentially be used to design and evaluate post-colonoscopy
      treatment strategies based on the risk of individual patients. To support model
      identification, observational longitudinal colonoscopy results, procedure
      details, and patient characteristics were collected for 4084 patients. We found
      that at least two parameter sets specific to each sex with model adjustments was
      required to capture the longitudinal colonoscopy data and inclusion of multiple
      possible parameter set combinations, which account for random variations within
      the population, was necessary to accurately predict the second-time colonoscopy
      findings for patients with a history of advanced adenomas. Application of this
      model to predict CRC risks for patients adhering to guideline recommended follow
      up colonoscopy intervals found that there are significant differences in risk
      with patient age, gender, and preparation quality and demonstrates the need for a
      more rigorous investigation into these recommendations.

PMID- 23968896
TI  - Macrolide-resistant Mycoplasma pneumoniae in humans, Ontario, Canada, 2010-2011.
AB  - Antimicrobial drug resistance rates for Mycoplasma pneumoniae was determined in
      clinical specimens and isolates obtained during 2011-2012 in Ontario, Canada. Of
      91 M. pneumoniae drug-resistant specimens, 11 (12.1%) carried nucleotide
      mutations associated with macrolide resistance in the 23S rRNA gene. None of the
      M. pneumoniae specimens were resistant to fluoroquinolones or tetracyclines.

PMID- 23968895
TI  - Diversity of cell death pathways: insight from the fly ovary.
AB  - Multiple types of cell death exist including necrosis, apoptosis, and autophagic
      cell death. The Drosophila ovary provides a valuable model to study the diversity
      of cell death modalities, and we review recent progress to elucidate these
      pathways. At least five distinct types of cell death occur in the ovary, and we
      focus on two that have been studied extensively. Cell death of mid-stage egg
      chambers occurs through a novel caspase-dependent pathway that involves autophagy
      and triggers phagocytosis by surrounding somatic epithelial cells. For every egg,
      15 germline nurse cells undergo developmental programmed cell death, which occurs
      independently of most known cell death genes. These forms of cell death are
      strikingly similar to cell death observed in the germlines of other organisms. 

PMID- 23968897
TI  - Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5
      thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones.
AB  - In our lead finding program, a series of 5-thioxo-[1,2,4]triazolo[1,5
      a][1,3,5]triazin-7-ones and their 5-thio-alkyl derivatives were designed and
      synthesized which contained different substituents at ortho-position of 2-phenyl
      ring attached to the fused ring structure. The preliminary pharmacological
      evaluation demonstrated that the synthesized compounds exhibited a varying degree
      of inhibitory activity towards thymidine phosphorylase (TP), comparable to
      reference compound, 7-Deazaxanthine (7-DX, 2) (IC50 value=42.63 MUM). The study
      also inferred that the ortho-substituted group at the phenyl ring and 5-thio
      alkyl moiety imparted steric hindrance effects in the binding site of the enzyme,
      leading to a reduced inhibitory response. In addition, compound 3a was identified
      as a mixed-type inhibitor of TP. Moreover, computational docking study was
      performed to illustrate the important structural information on the plausible
      ligand-enzyme binding interactions.

PMID- 23968898
TI  - Reducing hospital readmissions for cardiovascular disease: is it feasible?

PMID- 23968899
TI  - Juicing is not all juicy.

PMID- 23968900
TI  - Methadone and torsade de pointes: how can we better understand the association?

PMID- 23968901
TI  - Wretched excess: stool-softener abuse and cardiogenic shock.

PMID- 23968902
TI  - Risk of emergent bradycardia associated with the use of carvedilol and metoprolol
      in routine clinical practice.
AB  - BACKGROUND: Large randomized trials have reported mixed results regarding the
      risk of bradycardia between metoprolol and carvedilol. We compared the incidence
      of emergent bradycardia (measured by an emergency department visit or
      hospitalization due to bradycardia) for patients initiating metoprolol and
      carvedilol. METHODS: Adult beneficiaries of Medi-Cal, the State of California
      Medicaid program, without a diagnosis of bradycardia who initiated metoprolol or
      carvedilol between May 1, 2004, and November 1, 2009, were included. Cox
      proportional hazard regression analysis was performed to model the time to first
      occurrence of emergent bradycardia after initiation of the study drugs as a
      dependent variable and the study drug (metoprolol vs carvedilol) as the primary
      predictor with adjustments for total daily metoprolol-equivalent dose,
      formulations, and use of nonstudy drugs as time-varying covariates, as well as
      demographics and comorbidities. RESULTS: Among 38,186 subjects, 77.7% initiated
      metoprolol and 22.3% initiated carvedilol. The incidence of emergent bradycardia
      was low and comparable between the drugs (18.1 per 1000 person-years using
      metoprolol vs 17.7 per 100 person-years using carvedilol; unadjusted hazard
      ratio, 1.07; 95% confidence interval, 0.76-1.49). However, carvedilol users had
      substantially different population characteristics compared with metoprolol
      users. After adjustments for demographics, comorbidities, metoprolol-equivalent
      dose, formulations, and use of nonstudy drugs, initiation of metoprolol was
      associated with an increased risk of emergent bradycardia compared with that of
      carvedilol (adjusted hazard ratio, 1.64; 95% confidence interval, 1.14-2.36).
      CONCLUSIONS: Initiation of metoprolol is associated with an increased risk of
      emergent bradycardia compared with carvedilol, although the overall incidence of
      emergent bradycardia is low in routine clinical practice.

PMID- 23968903
TI  - Case fatality rate with vena cava filters in hospitalized stable patients with
      cancer and pulmonary embolism.
AB  - BACKGROUND: In view of the high risk of pulmonary embolism in patients with
      cancer, we tested the hypothesis that stable patients with pulmonary embolism who
      have cancer might be a subset of patients who would show a lower case fatality
      rate with vena cava filters than without filters. METHODS: Stable patients with
      pulmonary embolism and cancer at discharge from short-stay hospitals throughout
      the US from 1998-2009 were identified from the Nationwide Inpatient Sample.
      Patients with pulmonary embolism who had a diagnostic code for shock, ventilatory
      support, thrombolytic therapy, or pulmonary embolectomy were excluded because
      such patients have been shown to have lower case fatality rate with filters.
      RESULTS: In-hospital all-cause case fatality rate was lower with vena cava
      filters in stable patients with pulmonary embolism and solid malignant tumors
      providing they were aged >30 years, but there was variability according to type
      of tumor and age of patient. On average, case fatality rate among those >30 years
      with filters was 7070 of 69,350 (10.2%) (95% confidence interval, 10.0-10.4)
      versus 36,875 of 247,125 (14.9%) (95% confidence interval, 14.8-15.1) without
      filters (P <.0001) (relative risk 0.68). Among stable patients with hematological
      malignancies, case fatality rate, except in the elderly, was higher among those
      with vena cava filters than those without filters. CONCLUSION: Stable patients
      with pulmonary embolism and solid malignant tumors who are older than age 30
      years appear to be a subset of patients with pulmonary embolism who would benefit
      from vena cava filters, but this needs to be tested prospectively.

PMID- 23968904
TI  - Teaching high-value, cost-conscious care: improving residents' knowledge and
      attitudes.

PMID- 23968905
TI  - The reply.

PMID- 23968906
TI  - Incidence of sodium polystyrene sulfonate-associated colonic necrosis.

PMID- 23968907
TI  - The reply.

PMID- 23968908
TI  - Unrecognized pulmonary embolism may have simulated arrhythmogenic pneumonia.

PMID- 23968909
TI  - A diagnostic blind spot: acute infectious mononucleosis or acute retroviral
      syndrome.

PMID- 23968910
TI  - Rosuvastatin is transferred into human breast milk: a case report.

PMID- 23968911
TI  - Assay characteristics and diagnostic improvement from contemporary to high
      sensitivity troponin I immunoassays.

PMID- 23968912
TI  - Development of effluent removal prediction model efficiency in septic sludge
      treatment plant through clonal selection algorithm.
AB  - This study aims at developing a novel effluent removal management tool for septic
      sludge treatment plants (SSTP) using a clonal selection algorithm (CSA). The
      proposed CSA articulates the idea of utilizing an artificial immune system (AIS)
      to identify the behaviour of the SSTP, that is, using a sequence batch reactor
      (SBR) technology for treatment processes. The novelty of this study is the
      development of a predictive SSTP model for effluent discharge adopting the human
      immune system. Septic sludge from the individual septic tanks and package plants
      will be desuldged and treated in SSTP before discharging the wastewater into a
      waterway. The Borneo Island of Sarawak is selected as the case study. Currently,
      there are only two SSTPs in Sarawak, namely the Matang SSTP and the Sibu SSTP,
      and they are both using SBR technology. Monthly effluent discharges from 2007 to
      2011 in the Matang SSTP are used in this study. Cross-validation is performed
      using data from the Sibu SSTP from April 2011 to July 2012. Both chemical oxygen
      demand (COD) and total suspended solids (TSS) in the effluent were analysed in
      this study. The model was validated and tested before forecasting the future
      effluent performance. The CSA-based SSTP model was simulated using MATLAB 7.10.
      The root mean square error (RMSE), mean absolute percentage error (MAPE), and
      correction coefficient (R) were used as performance indexes. In this study, it
      was found that the proposed prediction model was successful up to 84 months for
      the COD and 109 months for the TSS. In conclusion, the proposed CSA-based SSTP
      prediction model is indeed beneficial as an engineering tool to forecast the long
      run performance of the SSTP and in turn, prevents infringement of future
      environmental balance in other towns in Sarawak. 

PMID- 23968913
TI  - An innovative sewage sludge reduction by using a combined mesophilic anaerobic
      and thermophilic aerobic process with thermal-alkaline treatment and sludge
      recirculation.
AB  - Lab-scale High Efficiency Digestion (HED) systems containing a Mesophilic
      Anaerobic Reactor (MAR), Thermophilic Aerobic Reactor (TAR), liquid/solid
      separation unit, and thermal-alkaline treatment were developed to evaluate the
      efficiencies of sludge reduction and methane production. The HED process was
      divided into three phases to examine the influence of sludge pretreatment and
      pretreated sludge recirculation using TCOD and VSS reduction, COD solubilization,
      and methane production. The VSS removal with a solid/liquid separation unit,
      sludge recirculation, and thermal-alkaline treatment drastically increased up to
      95% compared to the feed concentration. In addition, the results of COD
      solubilization and VSS/TSS showed that the solubilization of cells and organic
      matters by the thermal-alkaline treatment was highly increased, which was also
      consistent with the SEM images. In particular, the methane production rate
      increased 24-fold when the feed sludge and recirculated sludge were pretreated
      together. Collectively, the HED experiments performed with sludge recirculation
      and thermal-alkaline treatment demonstrated that the HED systems can be
      successfully employed for highly efficient sewage sludge reduction and methane
      gas production. 

PMID- 23968914
TI  - Synergistic inhibition of cell migration by tetraspanin CD82 and gangliosides
      occurs via the EGFR or cMet-activated Pl3K/Akt signalling pathway.
AB  - The metastasis suppressor CD82/KAI-1, which is a member of the tetraspanin
      superfamily, has been proposed to exert its activity together with
      glycosphingolipids. However, the mechanism of CD82 inhibition has not been fully
      elucidated. The present study aimed to investigate the synergistic inhibition of
      cell migration by the tetraspanin CD82 and gangliosides and to correlate this
      inhibition with activation of epidermal growth factor receptor (EGFR) and
      hepatocyte growth factor receptor (HGFR/cMet) in Hepa1-6 cell lines, whose
      motility and migration is stimulated by epidermal growth factor (EGF) and
      hepatocyte growth factor (HGF) in vitro. We found that Hepa1-6 cells transfected
      with the CD82 gene exhibited decreased migration in response to EGF and HGF. EGF
      stimulated phosphorylation of EGFR at Tyr1173 was inhibited in these cells, which
      contributed to the attenuation of EGFR. Ectopic expression of CD82 in Hepa1-6
      cells inhibited HGF-stimulated tyrosine phosphorylation of cMet at Tyr1313 and
      Tyr1365 without affecting the expression of cMet. These inhibitory effects were
      enhanced when CD82 was introduced with Ganglioside GM3 alone or GM2/GM3.
      Reduction of CD82 expression by RNA interference together with depletion of
      glycosphingolipids with P4 significantly enhanced cell motility and increased the
      expression of EGFR and its phosphorylation at Tyr1173 in response to EGF.
      Increased cell motility and HGF-dependent activation of cMet at Tyr1313 and
      Tyr1365 resulted from decreased CD82 levels and increased GM3. Furthermore, CD82
      expression selectively attenuated EGFR and cMet signalling via
      phosphatidylinositol 3-kinase/Akt but had no affect on the activity of the MAPK
      signalling pathway. These results suggest that the synergistic effects of CD82
      and GM3 or GM2/GM3 on EGFR expression and phosphorylation and cMet activation are
      responsible for CD82 inhibition of EGF- and HGF-dependent cell motility and
      migration of Hepa1-6 cells. 

PMID- 23968915
TI  - Fibromuscular dysplasia of cardiac conduction system arteries in traumatic and
      nonnatural sudden death victims aged 0 to 40 years: a histological analysis of
      100 cases.
AB  - BACKGROUND: Since 1967, numerous case reports have described fibromuscular
      alterations of the sinus node artery and/or the atrioventricular node artery as a
      potential cause of death. However, the prevalence of these changes in a healthy
      population has only rarely been investigated systematically. METHODS: The
      arteries of the cardiac conduction system were studied systematically, by means
      of routine histology, in 100 cases of victims aged 0 to 40 years with a
      nonnatural cause of death. RESULTS: Microscopic alterations were seen in the
      walls of sinus node arteries in 52 out of 100 cases, in the walls of
      atrioventricular node arteries in 63/100 cases, and in the walls of small vessels
      in 60/100 cases. CONCLUSIONS: The results demonstrate that microscopically
      detectable findings of the cardiac conduction system arteries similar to
      fibromuscular dysplasia do not indicate a defined disease and should not be
      considered as a cause of death when there are no macroscopic findings in the
      coronary arteries.

PMID- 23968917
TI  - Pearls.

PMID- 23968916
TI  - Low NK cell counts in peripheral blood are associated with inferior overall
      survival in patients with follicular lymphoma.
AB  - Host immune responses influence follicular lymphoma (FL) outcomes. To test our
      hypothesis that immune cells in blood reflect that response, we assessed by
      peripheral blood flow cytometry in 75 untreated FL patients the absolute counts
      of: lymphocytes (ALC), CD4(+)T (ACD4C), CD8(+)T (ACD8C) and natural killer (ANKC)
      cells. Low ANKC was the only parameter associated with inferior overall survival
      by univariate analysis (p=0.02), and trended to significance in multivariable
      analysis with ACD4C (p=0.08). Five (24%) patients with low initial ANKC died,
      while one (2%) with normal/high ANKC has died. In conclusion, evaluation of blood
      ANKC may be a useful indicator of outcome in previously untreated FL patients. 

PMID- 23968918
TI  - Intelligence.
AB  - Some people are cleverer than others. I think it would be a good thing if more
      biologists began with that observation as the starting point for their research.
      Why? Because it is a prominent and consistent way in which people differ from
      each other; because the measurements we make of people's cleverness produce
      scores that are correlated with important life outcomes; because it is
      interesting to discover the mechanisms that produce these individual differences;
      and because understanding these mechanisms might help to ameliorate those states
      in which cognitive function is low or declining.

PMID- 23968919
TI  - Olfaction: it makes a world of scents.
AB  - Mutations in odorant receptor genes predict olfactory perception of common
      compounds in foods and flowers. Through recombination they can generate extensive
      combinatorial variation in sensory ability among individuals. 

PMID- 23968920
TI  - Evolution: one thread to unite them all.
AB  - Mitochondria play import roles in the overall metabolism of eukaryotes.
      Traditionally, they have played a secondary role to the nucleus in the origin of
      eukaryotes. However, their relative positions in this crucial event for
      eukaryotic evolution might be reversed. 

PMID- 23968921
TI  - Vision: more than expected in the early visual system.
AB  - In the standard model of central visual processing, orientation tuned responses
      in cortex are built from untuned thalamic inputs. But recent studies in the mouse
      show orientation selectivity in thalamic neurons, and address their potential
      source and possible roles in cortical computation. 

PMID- 23968922
TI  - Calcium signaling: septins organize the SOC channel.
AB  - Store-operated Ca(2+) entry is a widely encountered mechanism for generating
      cytoplasmic Ca(2+) signals. From a whole-genome screen in HeLa cells, a new study
      reveals that cytoskeletal septins play a critical role in this process, by
      organizing signaling structures in the plasma membrane. 

PMID- 23968923
TI  - Location memory: separate cortical coding for distal and local cues.
AB  - Entorhinal cortex is implicated in coding the location of spatial cues: a new
      study has found that distinct regions of entorhinal cortex respond differentially
      to distal versus local cues when these cues are rotated in conflict with one
      another. 

PMID- 23968924
TI  - Dendrite plasticity: branching out for greener pastures.
AB  - Environmental stress triggers substantial alterations in animal physiology and,
      in some cases, brain structure. Using the nematode Caenorhabditis elegans, a new
      study reports that unfavorable conditions lead to dramatic dendrite remodeling in
      neurons that mediate an adaptive dispersal behavior. 

PMID- 23968925
TI  - Circadian biology: sleep-styles shaped by light-styles.
AB  - Light and darkness are the main time cues synchronising all biological clocks to
      the external environment. This little understood evolutionary phenomenon is
      called circadian entrainment. A new study illuminates our understanding of how
      modern light- and lifestyles compromise circadian entrainment and impact our
      biological clocks. 

PMID- 23968926
TI  - Structural Biology: Parkin's Serpentine Shape Revealed in the Year of the Snake.
AB  - Parkin is an E3 ubiquitin ligase, mutations in which are responsible for
      autosomal recessive juvenile parkinsonism. Recently, several structures of Parkin
      have been solved, revealing its serpentine shape and modes of auto-inhibition. 

PMID- 23968927
TI  - Higher-order figure discrimination in fly and human vision.
AB  - Visually-guided animals rely on their ability to stabilize the panorama and
      simultaneously track salient objects, or figures, that are distinct from the
      background in order to avoid predators, pursue food resources and mates, and
      navigate spatially. Visual figures are distinguished by luminance signals that
      produce coherent motion cues as well as more enigmatic 'higher-order' statistical
      features. Figure discrimination is thus a complex form of motion vision requiring
      specialized neural processing. In this minireview, we will highlight recent
      advances in understanding the perceptual, behavioral, and neurophysiological
      basis of higher-order figure detection in flies, much of which is grounded in the
      historical perspective and mechanistic underpinnings of human psychophysics.

PMID- 23968928
TI  - Molecular cloning and expression analysis of PDR1-like gene in ginseng subjected
      to salt and cold stresses or hormonal treatment.
AB  - The plant pleiotropic drug resistance (PDR) family of ATP-binding cassette (ABC)
      transporters is potentially involved in diverse biological processes. Currently,
      little is known about their actual physiological functions. A Panax ginseng PDR
      transporter gene (PgPDR1) was cloned and the cDNA has an open reading frame of
      4344 bp. The deduced amino acid sequence contained the characteristic domains of
      PDR transporters: Walker A, Walker B, and ABC signature. Genomic DNA
      hybridization analysis indicated that one copy of PgPDR1 gene was present in P.
      ginseng. Subcellular localization showed that PgPDR1-GFP fusion protein was
      specifically localized in the cell membrane. Promoter region analysis revealed
      the presence of cis-acting elements, some of which are putatively involved in
      response to hormone, light and stress. To understand the functional roles of
      PgPDR1, we investigated the expression patterns of PgPDR1 in different tissues
      and under various conditions. Quantitative real-time PCR (qRT-PCR) and Western
      blotting analysis showed that PgPDR1 was expressed at a high level in the roots
      and leaves compared to seeds and stems. The expression of PgPDR1 was up-regulated
      by salicylic acid (SA) or chilling, down-regulated by ABA, and regulated
      differently at transcript and protein levels by MeJA. These results suggest that
      PgPDR1 might be involved in responding to environmental stresses and hormones.

PMID- 23968929
TI  - Stress-responsive gene ICE1 from Vitis amurensis increases cold tolerance in
      tobacco.
AB  - We report the identification of the inducer of CBF expression 1 (ICE1) from Vitis
      amurensis, an upstream transcription factor that regulates the transcription of
      CBF-like genes. The structure of the basic helix-loop-helix domain of VaICE1 is
      closely related to that of ICE1 in woody plants. This gene is strongly induced in
      leaves, roots, stems, and petioles by cold temperature. With longer duration of
      exposure to cold treatments, the expression patterns of organs exhibit
      differences, which are not observed in normal condition. Transgenic tobacco over
      expressing VaICE1 has higher chilling tolerance and survival ability by improving
      the activities of superoxide dismutase, peroxidase, and catalase, as well as the
      chlorophyll yield. 

PMID- 23968930
TI  - A systemic response of geophytes is demonstrated by patterns of protein
      expression and the accumulation of signal molecules in Zantedeschia aethiopica.
AB  - In geophyte plants, such as Zantedeschia, individual leaves are directly
      connected to a specialized underground storage organ (rhizome/tuber), raising a
      question regarding systemic resistance as a mechanism of defense. A systemic
      response requires a transfer of a signal through the storage organ which has been
      evolutionary adapted to store food, minerals and moisture for seasonal growth and
      development. We have characterized the nature of induced defense responses in
      Zantedeschia aethiopica, a rhizomatous (tuber-like) ornamental plant by the
      application of local elicitation using two well-known defense elicitors, benzo
      (1,2,3)-thiadiazole-7-carbothioic acid S-methyl ester (BTH) and methyl jasmonate
      (MJ). The system consisted leaves in which local responses were directly induced,
      and systemically responsive leaves in which defense molecules were detected,
      demonstrating a transported vascular signal. Using anatomical and biochemical
      tools and local elicitation with MJ, the systemic nature of the response was
      verified in adjacent leaves by unique protein expression patterns; similarly
      polyphenol oxidase (PPO) activity was found to increase systemically in all parts
      of the locally induced plants, including the rhizome, and adjacent leaves;
      finally, significant accumulation of defense signal molecules such as salicylic
      and jasmonic acids was recorded in local and systemic leaves following
      elicitation with BTH. Anatomical sections through the leaves and the rhizome
      revealed that to be transferred from one leaf to its neighbor, signal molecules
      must have been transferred through the storage organ. The collected data strongly
      support our hypothesis that defense signals may and are transferred through the
      storage organ in monocot geophytes. 

PMID- 23968931
TI  - Persistence with cholinesterase inhibitor treatment in Alzheimer's disease.

PMID- 23968932
TI  - A real-world glimpse into the epidemiology of ALS in Canada.

PMID- 23968933
TI  - Hippocampal malrotation and temporal lobe epilepsy: what is the relationship?

PMID- 23968934
TI  - Mechanisms underlying taurine protection against glutamate-induced neurotoxicity.
AB  - Taurine appears to exert potent protections against glutamate (Glu)-induced
      injury to neurons, but the underlying molecular mechanisms are not fully
      understood. The possibly protected targets consist of the plasma membrane and the
      mitochondrial as well as endoplasmic reticulum (ER) membranes. Protection may be
      provided through a variety of effects, including the prevention of membrane
      depolarization, neuronal excitotoxicity and mitochondrial energy failure,
      increases in intracellular free calcium ([Ca2+]i), activation of calpain, and
      reduction of Bcl-2 levels. These activities are likely to be linked spatially and
      temporally in the neuroprotective functions of taurine. In addition, events that
      occur downstream of Glu stimulation, including altered enzymatic activities,
      apoptotic pathways, and necrosis triggered by the increased [Ca2+]i, can be
      inhibited by taurine. This review discusses the possible molecular mechanisms of
      taurine against Glu-induced neuronal injury, providing a better understanding of
      the protective processes, which might be helpful in the development of novel
      interventional strategies. 

PMID- 23968935
TI  - Mitochondrial depletion syndromes in children and adults.
AB  - To highlight differences between early-onset and adult mitochondrial depletion
      syndromes (MDS) concerning etiology and genetic background, pathogenesis,
      phenotype, clinical presentation and their outcome. MDSs most frequently occur in
      neonates, infants, or juveniles and more rarely in adolescents or adults. Mutated
      genes phenotypically presenting with adult-onset MDS include POLG1, TK2, TyMP,
      RRM2B, or PEO1/twinkle. Adult MDS manifest similarly to early-onset MDS, as
      myopathy, encephalo-myopathy, hepato-cerebral syndrome, or with chronic
      progressive external ophthalmoplegia (CPEO), fatigue, or only minimal muscular
      manifestations. Diagnostic work-up or treatment is not at variance from early
      onset cases. Histological examination of muscle may be normal but biochemical
      investigations may reveal multiple respiratory chain defects. The outcome appears
      to be more favorable in adult than in early-onset forms. Mitochondrial depletion
      syndromes is not only a condition of neonates, infants, or juveniles but rarely
      also occurs in adults, presenting with minimal manifestations or manifestations
      like in the early-onset forms. Outcome of adult-onset MDS appears more favorable
      than early-onset MDS. 

PMID- 23968936
TI  - Unique experiences with intercontinental trials in stroke - part II.
AB  - Supported by the Canadian Medical Research Council we performed a randomized
      trial extending from Newfoundland to British Columbia. With others a number of
      observations showed that aspirin will reduce stroke. With National Institute of
      Neurological Disorders and Stroke support we learned who would benefit and not
      from surgery in these stroke threatened carotid diseased patients. We evaluated
      the upper limits of acceptability of complications beyond which harm was done.
      Amassing this large data base of approximately 5000 individuals, followed for
      five years, previously unknown carotid phenomena were observed: 1. Ischemic
      stroke occurs in patients with prolapsing mitral valves; 2. There is risk of
      stroke in patients with residual thrombi in the occluded stump of the carotid
      artery; 3. We detected a lower risk than expected in patients with nearly
      occluded carotid arteries. We support the contention of Yusuf and Cairns' that
      Canada needs to give more financial support to purely clinical research. It pays
      off ! 

PMID- 23968938
TI  - Visual hallucinations and cognitive impairment in Parkinson's disease.
AB  - BACKGROUND: Visual hallucination (VH) is a common psychotic symptom in patients
      with Parkinson's disease (PD) and may be a significant predictor of cognitive
      impairment (CI) in such patients. OBJECTIVE: This study aimed to investigate the
      pattern of glucose metabolism of VH and the relationship between VH and CI in PD.
      METHODS: We studied 28 PD patients, including 15 with VH (PD-VH) and 13 without
      VH (PD-NVH). Of the 15 PD-VH patients, 8 patients had cognitive impairment (PD
      VHCI) whereas 7 did not (PD-VHNCI). All patients underwent [18F]
      fluorodeoxyglucose positron emission tomography ([18F] FDG PET) followed by
      statistical parametric mapping (SPM) analyses. RESULTS: Compared to the patients
      with PDNVH, PD-VHNCI patients showed glucose hypometabolism in the inferior and
      middle temporal cortices, fusiform gyri, and frontal areas, suggesting the
      involvement of the ventral visual pathway. Compared to the patients with PDNVH,
      PD-VHCI patients showed glucose hypometabolism in the temporoparietal association
      cortices with scattered frontal areas. CONCLUSION: Dysfunction of ventral visual
      pathway involving the temporal lobe may play a key role in VH development in PD
      patients. The evolving distribution from the ventral visual pathway to more
      extensive posterior cortices in PD-VHCI patients suggests that VH may be a
      prodromal symptom occurring prior to CI in PD patients.

PMID- 23968937
TI  - Hippocampal malrotation is associated with chromosome 22q11.2 microdeletion.
AB  - BACKGROUND: Patients with chromosome 22q11.2 deletion syndrome (22q11DS) are at a
      seven fold increased risk of developing seizures. However, only a fraction of
      these patients exhibit structural abnormalities such as polymicrogyria (PMG) and
      periventricular nodular heterotopia (PNH) that are known to cause seizures and to
      be associated with 22q11DS. In this study we used a dedicated seizure imaging
      protocol to look for additional structural abnormalities in these individuals
      that may explain the elevated risk of seizure disorder in this patient group.
      METHODS: Nineteen consecutive adult subjects with 22q11DS underwent a 3 Tesla MRI
      with a dedicated high-resolution seizure protocol. Neurological exam was
      performed in all patients. Genome-wide analysis excluded the presence of other
      pathogenic microdeletions or duplications. RESULTS: Structural abnormalities were
      found in 11 of 14 subjects with sufficient image quality. These included three
      patients with PNH, one of whom had associated PMG. In addition, there was a
      surprisingly high prevalence of unilateral hippocampal malrotation (HIMAL),
      observed in 9 of 14 cases (64%). EEG findings showed interictal epileptiform
      discharges with focal distribution in four patients and generalized discharges in
      one patient. CONCLUSION: The results suggest that, in addition to other known
      structural abnormalities, 22q11DS is associated with HIMAL. It has been suggested
      that this developmental abnormality of the hippocampus may predispose or
      otherwise contribute to epileptogenesis. However in this study we observed HIMAL
      in a large proportion of patients, with and without epilepsy. Therefore, other as
      yet unknown factors may contribute to the high prevalence of epilepsy in this
      population.

PMID- 23968939
TI  - Effectiveness of BoNT A in Parkinson's disease upper limb tremor management.
AB  - OBJECTIVE: One the greatest challenges of BoNT A therapy for tremor lies in the
      complexity and variation of components involved in tremor movement, and the lack
      of objective measures to determine these components. This 3 month open-label
      single injection study aims to couple clinician best judgment with kinematics to
      improve effect of BoNT A (incobotulinumtoxinA) injection in 7 patients with upper
      limb Parkinson's disease (PD) tremor. METHODS: Injection was guided with clinical
      and kinematic assessment of tremor using angular wrist position in 3 degrees of
      freedom: flexion/extension, pronation/supination, and radial/ulnar deviation.
      Overall tremor severity and change were measured by linear finger acceleration.
      RESULTS: Kinematic data from static and functional tasks demonstrate no
      improvement at one month post-injection, but significant improvement at two and
      three months. Clinical scales across UPDRS Items 20 (1, 2, 3 months post) and 21
      (2 months), and spiral drawings (3 months) showed significant improvement from
      baseline, while line drawings did not. CONCLUSIONS: This study suggests injection
      of BoNT A as a viable focal management option for upper limb PD tremor. In
      addition to clinical judgment, objective quantification of tremor dynamics by
      kinematics may be a feasible assessment and guidance tool which can be used to
      optimize injection conditions for focal tremor therapy. Kinematic analysis of
      tremor across a variety of joints in all degrees of movement may provide
      important insight into tremor dynamics, allowing optimized, targeted focal
      therapy.

PMID- 23968940
TI  - Discrimination of the cognitive profiles of MCI and depression using the KBNA.
AB  - OBJECTIVE: The current study sought to determine if the Kaplan-Baycrest
      Neurocognitive Assessment (KBNA) was capable of discriminating individuals with
      subjective memory complaints associated with depression from individuals with
      mild cognitive impairment (MCI). METHODS: Scores on 12 subtests of the KBNA were
      compared for 27 participants with MCI and 28 participants being treated for
      depression using Bonferroni correct between-group comparisons for each subtest.
      KBNA subtest scores were corrected for age and education. RESULTS: Significant
      between-group differences were obtained on six subtests with large effect sizes
      (Cohen's d) ranging from 1.19 - 1.58. The six subtests involved encoding and
      delayed episodic memory for verbal and visual information. Using logistic
      regression analysis, five subtests of the KBNA were able to correctly classify
      96.4% of study participants. CONCLUSION: The results from this preliminary
      investigation indicate that the KBNA has the potential to serve as a brief and
      reliable assessment tool capable of distinguishing individuals with subjective
      memory complaints associated with depression from individuals with MCI in a
      clinical setting. Limitations of the current study and future research are
      discussed.

PMID- 23968941
TI  - Correcting the MoCA for education: effect on sensitivity.
AB  - OBJECTIVE: The goal of this study was to quantify the impact of the suggested
      education correction on the sensitivity and specificity of the Montreal Cognitive
      Assessment (MoCA). METHOD: Twenty-five outpatients with dementia and 39 with
      amnestic mild cognitive impairment (aMCI) underwent a diagnostic evaluation,
      which included the MoCA. Thirty-seven healthy controls also completed the MoCA
      and psychiatric, medical, neurological, functional, and cognitive difficulties
      were ruled out. RESULTS: For the total MoCA score, unadjusted for education, a
      cut-off score of 26 yielded the best balance between sensitivity and specificity
      (80% and 89% respectively) in identifying cognitive impairment (people with
      either dementia or aMCI, versus controls). When applying the education
      correction, sensitivity decreased from 80% to 69% for a small specificity
      increase (89% to 92%). The cut-off score yielding the best balance between
      sensitivity and specificity for the education adjusted MoCA score fell to 25 (61%
      and 97%, respectively). CONCLUSIONS: Adjusting the MoCA total score for education
      had a detrimental effect on sensitivity with only a slight increase in
      specificity. Clinically, this loss in sensitivity can lead to an increased number
      of false negatives, as education level does not always correlate to premorbid
      intellectual function. Clinical judgment about premorbid status should guide
      interpretation. However, as this effect may be cohort specific, age and education
      corrected norms and cut-offs should be developed to help guide MoCA
      interpretation.

PMID- 23968942
TI  - Less education predicts anticholinesterase discontinuation in dementia patients.
AB  - OBJECTIVE: We investigated patient socio-demographic, clinical and functional
      factors predicting cholinesterase inhibitor discontinuation by patients
      presenting to a memory clinic in Saskatoon, Saskatchewan. METHODS: Data
      collection began in March 2004 at the Rural and Remote Memory Clinic where family
      physicians referred their non-institutionalized patients. Neurological and
      neuropsychological assessment, patient and caregiver questionnaires provided the
      socio-demographic, clinical and functional variables. Univariate logistic
      regression analysis was used to examine possible associations between each
      independent variable and the binary outcome variable of treatment
      discontinuation. Multivariate logistic regression was used to determine
      predictors of cholinesterase inhibitor discontinuation within six months of drug
      initiation. RESULTS: Our sample consisted of the first 63 patients (60.3% female)
      for whom we prescribed a cholinesterase inhibitor. The mean age at clinic day was
      74.56 years (SD=7.78). We found that years of formal education was the only
      variable significantly associated with cholinesterase inhibitor discontinuation
      by six months. The more years of formal education, the lower the rate of drug
      discontinuation by six months. CONCLUSIONS: Likelihood of cholinesterase
      inhibitor discontinuation by six months was predicted by fewer years of formal
      education.

PMID- 23968943
TI  - Meta-analysis on the association between the TF gene rs1049296 and AD.
AB  - BACKGROUND: Polymorphisms of genes participating in iron transportation have been
      associated with Alzheimer's disease (AD) risk. The association between
      transferrin (TF) gene rs1049296 (P570S) polymorphism and AD is controversial.
      METHODS: We performed meta analysis on data from 19 studies with 6310 cases and
      13661 controls to reexamine the association between the TF gene rs1049296
      polymorphism and AD. We applied a fixed-effects model to combine the odds ratio
      (OR) and 95% confidence intervals (95% CI). Egger's test was carried out to
      evaluate the potential publication bias. RESULTS: The overall ORs with 95% CIs
      showed statistical association between the TF gene rs1049296 polymorphism and the
      risk of AD in the allele contrast, the recessive model and the dominant model for
      allele C2 (fixed-effects pooled OR 1.11; 95% CI 1.05 to 1.17, pooled OR 1.13; 95%
      CI 1.06 to 1.21, and pooled OR 1.23; 95% CI 1.03 to 1.47, respectively). In the
      contrast of C2C2+C2C1 vs C1C1, large heterogeneity among the Asian subgroup
      (p=0.041, I2= 68.6%) was observed but not among the overall population (p =
      0.184, I2= 22.4%). No publication bias was observed. CONCLUSIONS: The present
      meta analysis demonstrated that TF gene rs1049296 polymorphism is a genetic
      determinant of AD.

PMID- 23968945
TI  - Epidemiological surveillance of amyotrophic lateral sclerosis in Saguenay region.
AB  - OBJECTIVES: The Neuromuscular Registry of Saguenay-Lac-Saint-Jean (SLSJ), Quebec,
      Canada was established for epidemiological surveillance of neuromuscular
      disorders including amyotrophic lateral sclerosis (ALS). The objectives of this
      study are to analyze the ALS clinical characteristics of the SLSJ population and
      to determine the incidence rate over time by five year periods since 1985.
      METHODS: The Registry was validated by a review of the medical records maintained
      at the CSSS de Chicoutimi, the regional university hospital and, by the
      estimation of the number of hospitalizations for ALS patients using the Quebec
      Hospital inpatient database (MED-ECHO). RESULTS: A total of 109 patients were
      included. Overall, the clinical features of ALS observed in SLSJ population are
      similar to those described in the literature. We observed a significant increase
      in the incidence rate of ALS during the 2005-2009 period compared with the
      previous periods. This is due to a significant increase in the incidence rate
      among the >=65 years old group, from 4.68 per 100,000 persons/year (CI 95% 2.88
      6.48) during 1985-2004 period to 12.22 (CI 95% 7.43-17.02) during 2005-2009
      period. CONCLUSION: Given the small size of the SLSJ population, a longer
      observation period will be needed to confirm a new steady state incidence of ALS
      in this region.

PMID- 23968944
TI  - The CNDR: collaborating to translate new therapies for Canadians.
AB  - BACKGROUND: Patient registries represent an important method of organizing "real
      world" patient information for clinical and research purposes. Registries can
      facilitate clinical trial planning and recruitment and are particularly useful in
      this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are
      individually rare but in aggregate have a significant prevalence. In Canada,
      information on NMDs is lacking. Barriers to performing Canadian multicentre NMD
      research exist which can be overcome by a comprehensive and collaborative NMD
      registry. METHODS: We describe the objectives, design, feasibility and initial
      recruitment results for the Canadian Neuromuscular Disease Registry (CNDR).
      RESULTS: The CNDR is a clinic-based registry which launched nationally in June
      2011, incorporates paediatric and adult neuromuscular clinics in British
      Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of
      December 2012, has recruited 1161 patients from 12 provinces and territories.
      Complete medical datasets have been captured on 460 "index disease" patients.
      Another 618 "non-index" patients have been recruited with capture of physician
      confirmed diagnosis and contact information. We have demonstrated the feasibility
      of blended clinic and central office-based recruitment. "Index disease" patients
      recruited at the time of writing include 253 with Duchenne and Becker muscular
      dystrophy, 161 with myotonic dystrophy, and 71 with ALS. CONCLUSIONS: The CNDR is
      a new nationwide registry of patients with NMDs that represents an important
      advance in Canadian neuromuscular disease research capacity. It provides an
      innovative platform for organizing patient information to facilitate clinical
      research and to expedite translation of recent laboratory findings into human
      studies.

PMID- 23968946
TI  - Evaluation of a bicycle helmet safety program for children.
AB  - BACKGROUND: Helmets have been shown to decrease the risk of brain injury;
      however, helmets must be worn correctly and fit well in order to be effective.
      The objective of this study is to determine whether kindergarten-aged children
      could learn and retain appropriate helmet wearing technique through an
      educational bicycle safety program. METHODS: Retrospective analysis of scores in
      questionnaires administered before and after an educational intervention to
      kindergarten students four to six years of age. The study took place in Prince
      Edward Island, Canada. A Wilcoxon Sign-Rank Test was used to determine if there
      was a significant overall increase in knowledge; McNemar chi-square tests were
      used to determine if there was an increase in knowledge for individual questions.
      RESULTS: There was significant improvement in pre-test to immediate post-tests
      scores and pre-test to delay post-test scores when the results were stratified by
      age, sex, bike riding status, and helmet wearing status (p<0.001 for all
      comparisons). In particular, correct responses for the questions regarding
      appropriate helmet distances from the eyes increased from 38.9% in the pre-test
      to above 90% in the post-tests (p<0.001). Correct responses for the question
      pertaining to appropriate fitting of helmet straps increased from 71.7% pre-test
      to above 90% in the post-tests (p<0.001). CONCLUSIONS: There was improved
      knowledge of appropriate helmet-wearing technique among kindergarten-aged
      children as a result of the educational intervention, and knowledge gains were
      retained for at least one month.

PMID- 23968947
TI  - Spontaneous blink rates in children during different types of eye movements.
AB  - INTRODUCTION: The spontaneous blink rate (SBR) is variable in humans. It
      increases rapidly during childhood before reaching a plateau in adulthood at 10
      20 blinks/minute. Our aim was to compare the SBR during different visual tasks in
      children. METHODS: Thirty-nine healthy participants (mean age(SD):13.6(3.5)years,
      M=21), made horizontal and vertical visually-guided saccades, tracked a
      horizontal and vertical target, performed horizontal and vertical active
      sinusoidal head rotations in light and darkness while looking straight ahead (VOR
      task) or fixated straight ahead and in four directions of gaze. The eyes of each
      participant were videotaped and reviewed twice to determine the SBR. Parametric
      and non-parametric tests were used to analyze the data. RESULTS: The median SBR
      during fixation straight ahead was seven blinks/minute, which was similar to the
      SBR during horizontal saccades and horizontal smooth pursuit tasks. The median
      SBR during vertical smooth pursuit and vertical saccades were significantly lower
      than during fixation (p<=0.042). The median SBR during the VOR task in light and
      horizontal VOR in darkness were significantly higher than during fixation
      (p=0.019-0.024). CONCLUSIONS: The median SBR during visual fixation was lower
      than that reported previously in 5-14 years-old children during rest or 11-20
      years-old subjects during quiet conversation. The median SBR was even lower
      during vertical smooth pursuit and saccades tasks. This may be due to differences
      in concentration required for visual fixation in general and vertical visual
      tasks more specifically. The higher SBR during the VOR may be due to drying of
      the eyes during head shaking.

PMID- 23968948
TI  - Calcitonin gene related peptide gene polymorphism in migraine patients.
AB  - OBJECTIVE: Calcitonin gene related peptide (CGRP), which has a vasodilator
      effect, is held responsible for neurogenic inflammation and vasodilatation of the
      cranial vessels in migraine pathophysiology. In this study, we investigated the
      association between alpha CGRP gene polymorphism (CALCA T-692C) and migraine.
      MATERIAL AND METHODS: One hundred and thirty-four female migraineurs and 96
      healthy female cases were enrolled in the study. The patient group was further
      subdivided into migraine with and without aura groups. The CALCA T-692C gene
      polymorphism was identified using polymerase chain reaction (PCR) technique and
      restriction fragment length polymorphism (RFLP). RESULTS: The genotype and allele
      frequencies of CALCA T-692C gene polymorphism did not differ between the migraine
      and control groups. Between the migraine with and without aura subgroups, there
      was no difference. No association was seen between the CALCA T-692C gene
      polymorphisms and migraine attack severity and frequency. CONCLUSION: Our study
      did not show any association between CALCA T-692C gene polymorphism and migraine.

PMID- 23968949
TI  - Life experience and DNA polymorphisms influence the brain epigenome [corrected].

PMID- 23968950
TI  - A case of stroke and blindness.

PMID- 23968951
TI  - Intracardiac migration of a ventriculoperitoneal shunt.

PMID- 23968952
TI  - Preserved drawing in a sculptor with dementia.

PMID- 23968953
TI  - Acute-onset anterograde amnesia caused by isolated bilateral fornix infarction.

PMID- 23968954
TI  - Reversible parkinsonian features in deep cerebral venous sinus thrombosis.

PMID- 23968955
TI  - Pituitary abscess: review and highlight of a case mimicking pituitary apoplexy.

PMID- 23968956
TI  - Oligodendrogliomas with abundant refractile eosinophilic granular cells.

PMID- 23968958
TI  - Chronic inflammatory demyelinating polyneuropathy and metastatic melanoma.

PMID- 23968960
TI  - Prenatal maternal depression associates with microstructure of right amygdala in
      neonates at birth.
AB  - BACKGROUND: Antenatal maternal cortisol levels associate with alterations in the
      amygdala, a structure associated with emotion regulation, in the offspring.
      However, because offspring brain and behavior are commonly assessed years after
      birth, the timing of such maternal influences is unclear. This study aimed to
      examine the association between antenatal maternal depressive symptomatology and
      neonatal amygdala volume and microstructure and thus establish evidence for the
      transgenerational transmission of vulnerability for affective disorders during
      prenatal development. METHODS: Our study recruited Asian mothers at 10 to 13
      weeks pregnancy and assessed maternal depression at 26 weeks gestation using the
      Edinburgh Postnatal Depression Scale. Structural magnetic resonance imaging and
      diffusion tensor imaging were performed with 157 nonsedated, 6- to 14-day-old
      newborns and then analyzed to extract the volume, fractional anisotropy, and
      axial diffusivity values of the amygdala. RESULTS: Adjusting for household
      income, maternal age, and smoking exposure, postconceptual age at magnetic
      resonance imaging, and birth weight, we found significantly lower fractional
      anisotropy (p = .009) and axial diffusivity (p = .028), but not volume (p =
      .993), in the right amygdala in the infants of mothers with high compared with
      those with low-normal Edinburgh Postnatal Depression Scale scores. CONCLUSIONS:
      The results reveal a significant relation between antenatal maternal depression
      and the neonatal microstructure of the right amygdala, a brain region closely
      associated with stress reactivity and vulnerability for mood anxiety disorders.
      These findings suggest the prenatal transmission of vulnerability for depression
      from mother to child and that interventions targeting maternal depression should
      begin early in pregnancy.

PMID- 23968961
TI  - Regulatory mechanisms for glycogenolysis and K+ uptake in brain astrocytes.
AB  - Recent advances in brain energy metabolism support the notion that glycogen in
      astrocytes is necessary for the clearance of neuronally-released K(+) from the
      extracellular space. However, how the multiple metabolic pathways involved in
      K(+)-induced increase in glycogen turnover are regulated is only partly
      understood. Here we summarize the current knowledge about the mechanisms that
      control glycogen metabolism during enhanced K(+) uptake. We also describe the
      action of the ubiquitous Na(+)/K(+) ATPase for both ion transport and
      intracellular signaling cascades, and emphasize its importance in understanding
      the complex relation between glycogenolysis and K(+) uptake. 

PMID- 23968962
TI  - Fetal and maternal factors associated with neonatal adiposity as measured by air
      displacement plethysmography: a large cross-sectional study.
AB  - BACKGROUND: There is evidence that the fetal and early postnatal environments
      play a role in determining the risk of lifetime obesity, diabetes and
      cardiovascular disease. Neonatal body composition, as a surrogate marker of the
      in-utero environment, can be reliably and accurately measured by air displacement
      plethysmography (ADP). Our primary objective was to identify preconception, fetal
      and maternal factors affecting neonatal body composition. METHODS: This cross
      sectional study included 599 term babies born between September and October 2010
      at Royal Prince Alfred Hospital, Sydney, Australia. Neonatal body fat percentage
      (BF%) was measured within 48 h of birth using ADP. Maternal demographic,
      anthropometric and medical data as well as neonatal gestational age and sex were
      used to develop a regression model that predicted body composition and
      birthweight. RESULTS: The mean (SD) neonatal BF% in our whole population was
      9.2(4.4)%. Significant variables in the model for neonatal BF% were neonatal sex,
      gestational age, maternal ethnicity, gestational weight gain (GWG), pre-pregnancy
      BMI, parity and maternal hypertension (p<0.05); together, these explained 19% of
      the variation in BF%. GDM status was not a significant variable. Neonatal female
      sex, maternal Caucasian ethnicity and increased gestational weight gain explained
      the most variation and were most strongly associated with increased BF%.
      CONCLUSIONS: This study highlights maternal obesity and increased gestational
      weight gain as two factors that are amenable to intervention as risk factors for
      newborn adiposity, which is important in the future study of the "developmental
      origins of health and disease" hypothesis.

PMID- 23968963
TI  - Prepubertal gynecomastia in two monozygotic twins with Peutz-Jeghers syndrome:
      clinical and surgical management.

PMID- 23968964
TI  - A novel technique with aesthetic considerations in female-to-male transsexuals
      nipple areola complex reconstruction.

PMID- 23968965
TI  - A systematic review and meta-analysis of proton magnetic resonance spectroscopy
      and mismatch negativity in bipolar disorder.
AB  - Aberrant glutamate neurotransmission has been implicated in the pathophysiology
      of bipolar disorder with accumulating evidence from imaging, post-mortem and
      pathology studies. Studies investigating in vivo changes to the glutamatergic
      system have not been as consistent and warrant clarification. Studies utilizing
      proton-magnetic resonance spectroscopy ((1)H-MRS) have reported increased levels
      of combined glutamate and glutamine ("Glx"), which have been linked to
      impairments in N-methyl-d-aspartate (NMDA) receptor function. Similarly,
      neurophysiological studies utilising mismatch negativity (MMN) as an index of
      NMDA receptor function, have reported impairments in bipolar disorder. Here, we
      provide a systematic review of the literature in regards to the concentration of
      Glx and the magnitude of MMN in bipolar disorder. Separate meta-analyses revealed
      that bipolar disorder was associated with increased Glx concentration and
      decreased MMN-both measured frontally. The current findings corroborate previous
      evidence indicating that bipolar disorder is characterized by a perturbed frontal
      glutamate system. These observed changes in bipolar disorder might manifest as
      impairments in neuronal-glial interactions that lead to disrupted neuronal output
      and ultimately result in the characteristic neurocognitive sequelae associated
      with this disorder. 

PMID- 23968966
TI  - A new concept for early recovery after surgery for patients undergoing radical
      cystectomy for bladder cancer: results of a prospective randomized study.
AB  - PURPOSE: Early recovery after surgery concepts have gained wide acceptance in
      various surgical specialties. However, limited data are available for radical
      cystectomy. A new early recovery after surgery concept was compared to a more
      conservative regimen in patients undergoing radical cystectomy for bladder
      cancer. MATERIALS AND METHODS: A total of 101 consecutive patients were
      prospectively randomized to early recovery after surgery (62) or a conservative
      regimen (39) (intended randomization ratio was 2 early recovery after surgery-to
      1 conservative regimen). Primary end points were differences in quality of life,
      and secondary end points included postoperative morbidity, demand for analgesics,
      time spent in the intermediate care unit, mobility and number of gastrointestinal
      events during hospital stay. RESULTS: Quality of life parameters, as measured by
      the EORTC (European Organization for the Research and Treatment of Cancer)
      Quality of Life questionnaire QLQ-30 did not change significantly between
      postoperative days 3 and 7 and at discharge from hospital in the conservative
      regimen group, whereas a significant improvement was observed in the early
      recovery after surgery group. Postoperative morbidity was lower in the early
      recovery after surgery group in terms of wound healing disorders (p = 0.006),
      fever (p = 0.004) and thrombosis (p = 0.027). The demand for analgesics was
      significantly lower in the early recovery after surgery group. The amount of food
      consumed in relation to the amount of food offered was significantly higher for
      the early recovery after surgery group as early as day 3 (p = 0.02). Time spent
      in the intermediate care unit was significantly shorter for the early recovery
      after surgery group (p <0.001). There were no significant differences between the
      groups with respect to gastrointestinal events. The main limitations of this
      study were the lack of long-term data as well as the single center approach.
      CONCLUSIONS: Early recovery after surgery of patients who underwent radical
      cystectomy appears to have significant benefits compared to a conservative
      regimen in terms of postoperative morbidity, quality of life, use of analgesics
      and time spent in the intermediate care unit.

PMID- 23968967
TI  - Prevalence and management of lower urinary tract symptoms in methamphetamine
      abusers: an under-recognized clinical identity.
AB  - PURPOSE: We investigate the prevalence of lower urinary tract symptoms in a
      cohort of methamphetamine abusers, and assess the therapeutic efficacy of alpha
      blockers and anticholinergics. MATERIALS AND METHODS: From May 2011 to March
      2013, 78 male methamphetamine abusers diagnosed with methamphetamine addiction
      were identified at the National Forensic Hospital, Korea. The I-PSS
      (International Prostate Symptom Score) with consultation was used to investigate
      the prevalence of lower urinary tract symptoms, defined as total I-PSS 8 or
      greater and quality of life index score of 2 or greater. These values for
      methamphetamine abusers were compared to those of 71 age matched controls. alpha
      Blockers and anticholinergics were administered to methamphetamine abusers with
      lower urinary tract symptoms according to predominant voiding and storage
      symptoms based on voiding-to-storage subscore ratios. For methamphetamine abusers
      with no response, defined as a reduction of 4 or less in total I-PSS, an
      alternative drug or combination was administered. Efficacy was assessed based on
      a 4-week interval. RESULTS: The median periods of methamphetamine abuse and
      abstinence were 18.1 years and 5.7 months, respectively. Methamphetamine abusers
      showed a higher prevalence of lower urinary tract symptoms compared to controls
      (77% vs 15%, p <0.001), with higher I-PSS and quality of life index score (13.3
      vs 5.6 and 2.9 vs 0.9, respectively; p <0.001). Anticholinergics showed the
      greatest effect on I-PSS reduction with overall response rates for alpha
      blockers, anticholinergics and combinations of 13%, 61% and 14%, respectively.
      Seven (12%) methamphetamine abusers did not respond to any therapy. CONCLUSIONS:
      Lower urinary tract symptoms were highly prevalent among methamphetamine abusers.
      Our results imply that pathological dopaminergic mechanisms have a role in
      methamphetamine associated lower urinary tract symptoms. Moreover, first line
      anticholinergics and prompt combination with alpha-blockers conferred the most
      therapeutic benefit to nonresponders.

PMID- 23968968
TI  - Generalism and the evolution of parasite virulence.
AB  - The evolution of parasite-imposed host harm (virulence) will be affected by
      numerous factors, not least the range of hosts that parasites can infect. Here,
      we consider four ways that parasite host range (generalism) might directly affect
      observed levels of parasite virulence: costs of generalism, multiplicity of
      infection, maladaptive virulence, and host availability. Integrating parasite
      infectivity range with life-history evolution will generate novel general
      hypotheses for the evolutionary ecology of virulence, as well as explicit
      predictions about the virulence of emerging diseases resulting from host shifts. 

PMID- 23968969
TI  - The intermediate disturbance hypothesis is broadly defined, substantive issues
      are key: a reply to Sheil and Burslem.

PMID- 23968970
TI  - Molecular mechanisms involved in interleukin 1-beta (IL-1beta)-induced memory
      impairment. Modulation by alpha-melanocyte-stimulating hormone (alpha-MSH).
AB  - Pro-inflammatory cytokines can affect cognitive processes such as learning and
      memory. Particularly, interleukin-1beta (IL-1beta) influences the consolidation
      of hippocampus-dependent memories. We previously reported that administration of
      IL-1beta in dorsal hippocampus impaired contextual fear memory consolidation.
      Different mechanisms have been implicated in the action of IL-1beta on long-term
      potentiation (LTP), but the processes by which this inhibition occurs in vivo
      remain to be elucidated. We herein report that intrahippocampal injection of IL
      1beta induced a significant increase in p38 phosphorylation after contextual fear
      conditioning. Also, treatment with SB203580, an inhibitor of p38, reversed
      impairment induced by IL-1beta on conditioned fear behavior, indicating that this
      MAPK would be involved in the effect of the cytokine. We also showed that IL
      1beta administration produced a decrease in glutamate release from dorsal
      hippocampus synaptosomes and that treatment with SB203580 partially reversed this
      effect. Our results indicated that IL-1beta-induced impairment in memory
      consolidation could be mediated by a decrease in glutamate release. This
      hypothesis is sustained by the fact that treatment with d-cycloserine (DCS), a
      partial agonist of the NMDA receptor, reversed the effect of IL-1beta on
      contextual fear memory. Furthermore, we demonstrated that IL-1beta produced a
      temporal delay in ERK phosphorylation and that DCS administration reversed this
      effect. We also observed that intrahippocampal injection of IL-1beta decreased
      BDNF expression after contextual fear conditioning. We previously demonstrated
      that alpha-MSH reversed the detrimental effect of IL-1beta on memory
      consolidation. The present results demonstrate that alpha-MSH administration did
      not modify the decrease in glutamate release induced by IL-1beta. However,
      intrahippocampal injection of alpha-MSH prevented the effect on ERK
      phosphorylation and BDNF expression induced by IL-1beta after contextual fear
      conditioning. Therefore, in the present study we determine possible molecular
      mechanisms involved in the impairment induced by IL-1beta on fear memory
      consolidation. We also established how this effect could be modulated by alpha
      MSH. 

PMID- 23968972
TI  - Effects of shoe sole hardness on plantar pressure and comfort in older people
      with forefoot pain.
AB  - Plantar forefoot pain is common in older people and is related to increased peak
      pressures under the foot during gait. Variations in the hardness of the shoe sole
      may therefore influence both the magnitude of loading under the foot and the
      perceived comfort of the shoe in this population. The aim of this investigation
      was to determine the effect of varying shoe sole hardness on plantar pressures
      and comfort in older people with forefoot pain. In-shoe plantar pressures under
      the forefoot, midfoot and rearfoot were recorded from 35 older people (mean age
      73.2, SD 4.5 years) with current or previous forefoot pain using the pedar-X((r))
      system. Participants walked at their normal comfortable speed along an 8m walkway
      in shoes with three different levels of sole hardness: soft (Shore A25), medium
      (Shore A40) and hard (Shore A58). Shoe comfort was measured on a 100mm visual
      analogue scale. There were statistically significant differences in peak pressure
      of between 5% and 23% across the forefoot, midfoot and rearfoot (p<0.01). The
      hard-soled shoe registered the highest peak pressures and the soft-soled shoe the
      lowest peak pressures. However, no differences in comfort scores across the three
      shoe conditions were observed. These findings demonstrate that as shoe sole
      hardness increases, plantar pressure increases, however this does not appear to
      have a significant effect on shoe comfort.

PMID- 23968973
TI  - Response inhibition during avoidance of virtual obstacles while walking.
AB  - While walking, one often has to suppress and adjust a planned step in order to
      avoid a fall. Given that steps are preprogrammed this requires some form of motor
      inhibition. Motor inhibition is commonly tested in hand function and only
      recently attempts have been made to evaluate inhibition in the lower limbs,
      during step initiation. As adequate motor inhibition might play a role in
      avoiding falls a test to assess response inhibition during walking would be
      valuable. We developed a task in which subjects walked on a treadmill by stepping
      on projected patches of light, which could suddenly change color forcing the
      subjects to avoid it by shortening or lengthening their steps. The difficulty
      level was manipulated in 4 conditions by changing the distance available to
      respond. We hypothesized that larger demands on motor inhibition during walking
      would produce more failures and tested the performance of young adults (n=12) in
      order to establish the protocol for use in older adults. The failure rate on the
      walking test was analyzed. Reducing the available response distance by 150 mm
      from the easiest condition resulted in a significant increase in failure rates
      from 15.6% to 65.1%. Therefore, results indicate this novel test can be used to
      assess the level of motor inhibition during walking. Additionally, in comparison
      to previous literature on obstacle avoidance, our experiment shows that changing
      a precise aiming movement is considerably more challenging than changing the same
      movement executed automatically.

PMID- 23968971
TI  - CCL5 and cytokine expression in the rat brain: differential modulation by chronic
      morphine and morphine withdrawal.
AB  - Opioids have been shown to influence the immune system and to promote the
      expression of pro-inflammatory cytokines in the central nervous system. However,
      recent data have shown that activation of opioid receptors increases the
      expression and release of the neuroprotective chemokine CCL5 from astrocytes in
      vitro. To further define the interaction between CCL5 and inflammation in
      response to opioids, we have examined the effect of chronic morphine and morphine
      withdrawal on the in vivo expression of CCL5 as well as of pro-inflammatory
      cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF
      alpha). Rats undergoing a chronic morphine paradigm (10 mg/kg increasing to 30
      mg/kg, twice a day for 5 days) showed a twofold increase of CCL5 protein and mRNA
      within the cortex and striatum. No changes were observed in the levels of IL
      1beta and TNF-alpha. Naltrexone blocked the effect of morphine. A chronic
      morphine paradigm with no escalating doses (10 mg/kg, twice a day) did not alter
      CCL5 levels compared to saline-treated animals. On the contrary, rats undergoing
      spontaneous morphine withdrawal exhibited lower levels of CCL5 within the cortex
      as well as increased levels of pro-inflammatory cytokines and Iba-1 positive
      cells than saline-treated rats. Overall, these data suggest that morphine
      withdrawal may promote cytokines and other inflammatory responses that have the
      potential of exacerbating neuronal damage.

PMID- 23968974
TI  - Effects of dopamine replacement therapy on lower extremity kinetics and
      kinematics during a rapid force production task in persons with Parkinson
      disease.
AB  - Postural instability appears to be a dopamine resistance motor deficit in persons
      with Parkinson disease (PD); however, little is known about the effects of
      dopamine replacement on the relative biomechanical contributions of individual
      lower extremity joints during postural control tasks. To gain insight, we
      examined persons with PD using both clinical and laboratory measures. For a
      clinical measure of motor severity we utilized the Unified Parkinson Disease
      Rating Scale motor subsection during both OFF and ON medication conditions. For
      the laboratory measure we utilized data gathered during a rapid lower extremity
      force production task. Kinematic and kinetic variables at the hip, knee, and
      ankle were gathered during a counter movement jump during both OFF and ON
      medication conditions. Sixteen persons with PD with a median Hoehn and Yahr
      severity of 2.5 completed the study. Medication resulted in significant
      improvements of angular displacement for the hip, knee, and ankle. Furthermore,
      significant improvements were revealed only at the hip for peak net moments and
      average angular velocity compared to the OFF medication condition. These results
      suggest that dopamine replacement medication result in decreased clinical motor
      disease severity and have a greater influence on kinetics and kinematics
      proximally. This proximally focused improvement may be due to active recruitment
      of muscle force and reductions in passive restraint during lower extremity rapid
      force production. 

PMID- 23968975
TI  - Validity of using annual mean particulate matter concentrations as measured at
      fixed site in assessing personal exposure: an exposure assessment study in Japan.
AB  - From 2003 through 2005, we compared annual mean particulate matter (PM) and
      nitrogen dioxide (NO2) concentrations as measured at fixed-site monitoring
      stations in 6 Japanese cities with those measured inside and outside subject
      residences and during personal monitoring. A total of 65 households participated
      in indoor and outdoor residential exposure monitoring. In summer and autumn, we
      also performed personal monitoring of one resident of each household. On each
      day, personal samplers were used to collect 24-h samples of PM and NO2
      simultaneously from the fixed sites, indoor and outdoor, and from those
      undergoing personal monitoring. We found good correlations between the fixed-site
      and outdoor measurements for annual mean (average of 7-day * 4-season)
      concentrations of PM2.5, PM10-2.5, PM10 and NO2 (Spearman's rank correlation
      coefficients (rho) >= 0.75). However, the correlations between the fixed-site and
      indoor measurements were moderate to low. In summer and autumn, the correlations
      between the fixed-site and personal mean concentrations of PM2.5 (rho = 0.62),
      PM10 (rho = 0.58), and NO2 (rho = 0.70) were acceptable. However, because people
      spend most of their time indoors, these correlations for annual mean
      concentrations were not estimated to be high. Our results are important in
      allowing researchers to estimate the effects of resulting measurement errors of
      PM and NO2.

PMID- 23968976
TI  - Sodium-dependent phosphate cotransporters and phosphate-induced calcification of
      vascular smooth muscle cells: redundant roles for PiT-1 and PiT-2.
AB  - OBJECTIVE: Elevated serum phosphate has emerged as a major risk factor for
      vascular calcification. The sodium-dependent phosphate cotransporter, PiT-1, was
      previously shown to be required for phosphate-induced osteogenic differentiation
      and calcification of cultured human vascular smooth muscle cells (VSMCs), but its
      importance in vascular calcification in vivo and the potential role of its
      homologue, PiT-2, have not been determined. We investigated the in vivo
      requirement for PiT-1 in vascular calcification using a mouse model of chronic
      kidney disease and the potential compensatory role of PiT-2 using in vitro
      knockdown and overexpression strategies. APPROACH AND RESULTS: Mice with targeted
      deletion of PiT-1 in VSMCs were generated (PiT-1(Deltasm)). PiT-1 mRNA levels
      were undetectable, whereas PiT-2 mRNA levels were increased 2-fold in the
      vascular aortic media of PiT-1(Deltasm) compared with PiT-1(flox/flox) control.
      When arterial medial calcification was induced in PiT-1(Deltasm) and PiT
      1(flox/flox) by chronic kidney disease followed by dietary phosphate loading, the
      degree of aortic calcification was not different between genotypes, suggesting
      compensation by PiT-2. Consistent with this possibility, VSMCs isolated from PiT
      1(Deltasm) mice had no PiT-1 mRNA expression, increased PiT-2 mRNA levels, and no
      difference in sodium-dependent phosphate uptake or phosphate-induced matrix
      calcification compared with PiT-1(flox/flox) VSMCs. Knockdown of PiT-2 decreased
      phosphate uptake and phosphate-induced calcification of PiT-1(Deltasm) VSMCs.
      Furthermore, overexpression of PiT-2 restored these parameters in human PiT-1
      deficient VSMCs. CONCLUSIONS: PiT-2 can mediate phosphate uptake and
      calcification of VSMCs in the absence of PiT-1. Mechanistically, PiT-1 and PiT-2
      seem to serve redundant roles in phosphate-induced calcification of VSMCs.

PMID- 23968977
TI  - Saturated fatty acid palmitate aggravates neointima formation by promoting smooth
      muscle phenotypic modulation.
AB  - OBJECTIVE: Obesity is a major risk factor of atherosclerotic cardiovascular
      disease. Circulating free fatty acid levels are known to be elevated in obese
      individuals and, along with dietary saturated fatty acids, are known to associate
      with cardiovascular events. However, little is known about the molecular
      mechanisms by which free fatty acids are linked to cardiovascular disease.
      APPROACH AND RESULTS: We found that administration of palmitate, a major
      saturated free fatty acid, to mice markedly aggravated neointima formation
      induced by carotid artery ligation and that the neointima primarily consisted of
      phenotypically modulated smooth muscle cells (SMCs). In cultured SMCs, palmitate
      induced phenotypic modulation was characterized by downregulation of SMC
      differentiation markers, such as SM alpha-actin and SM-myosin heavy chain, and
      upregulation of mediators involved in inflammation and remodeling of the vessel
      wall, such as platelet-derived growth factor B and matrix metalloproteinases. We
      also found that palmitate induced the expression of proinflammatory genes via a
      novel toll-like receptor 4/myeloid differentiation primary response 88/nuclear
      factor-kappaB/NADPH oxidase 1/reactive oxygen species signaling pathway: nuclear
      factor-kappaB was activated by palmitate via toll-like receptor 4 and its
      adapter, MyD88, and once active, it transactivated Nox1, encoding NADPH oxidase
      1, a major reactive oxygen species generator in SMCs. Pharmacological inhibition
      and small interfering RNA-mediated knockdown of the components of this signaling
      pathway mitigated the palmitate-induced upregulation of proinflammatory genes.
      More importantly, Myd88 knockout mice were resistant to palmitate-induced
      exacerbation of neointima formation. CONCLUSIONS: Palmitate seems to promote
      neointima formation by inducing inflammatory phenotypes in SMCs.

PMID- 23968979
TI  - Expansion of the NKG2C+ natural killer-cell subset is associated with high-risk
      carotid atherosclerotic plaques in seropositive patients for human
      cytomegalovirus.
AB  - OBJECTIVE: Human cytomegalovirus (HCMV), a pathogen involved in the development
      and progression of atherosclerosis, promotes in some individuals a marked
      reconfiguration of the natural killer (NK)-cell compartment whose hallmark is a
      persistent expansion of a peripheral blood NK-cell subset expressing the
      CD94/NKG2C NK receptor. We aimed to evaluate whether the HCMV-associated NK-cell
      compartment reconfiguration is related to carotid atherosclerotic plaque (CAP)
      instability. APPROACH AND RESULTS: NK receptor expression (ie, LILRB1, NKG2A,
      NKG2C, and killer immunoglobulin-like receptors [KIR]) by peripheral NK and T
      cells was evaluated in 40 patients with HCMV+ with CAP, including
      nonatherosclerotic strokes (n=15) and healthy subjects (n=11) as controls. High
      risk CAP (n=16), defined as carotid stenosis >50% with ipsilateral neurological
      symptomatology in the previous 180 days, compared with non-high-risk CAP had
      higher %NKG2C+ NK cells (29.5 +/- 22.4% versus 16.3 +/- 13.2%; P=0.026; odds
      ratio, 1.053; 95% confidence interval, 1.002-1.106; P=0.042), with a
      corresponding reduction in the NKG2A+ NK subset (31.7 +/- 17.8% versus 41.8 +/-
      15.8%; P=0.072). The proportions of NKG2C+ NK cells in high-risk CAP were
      inversely correlated with the CD4+/CD8+ ratio (R(Spearman)=-0.629; P=0.009) and
      directly with high-sensitivity C-reactive protein levels (R(Pearson) = 0.591;
      P=0.012), consistent with higher subclinical systemic inflammation. The
      intraplaque inflammatory infiltrate, evaluated in 27 CAP obtained after
      endarterectomy, showed a higher presence of subintimal CD3+ lymphocytes in those
      patients with HCMV-induced changes in the peripheral NK- and T-cell compartments.
      CONCLUSIONS: The expansion of NKG2C+ NK cells in patients with CAP seems to be
      associated with an increased risk of plaque destabilization in some patients with
      chronic HCMV infection.

PMID- 23968978
TI  - Relationship among circulating inflammatory proteins, platelet gene expression,
      and cardiovascular risk.
AB  - OBJECTIVE: Cardiovascular disease is a complex disorder influenced by
      interactions of genetic variants with environmental factors. However, there is no
      information from large community-based studies examining the relationship of
      circulating cell-specific RNA to inflammatory proteins. In light of the
      associations among inflammatory biomarkers, obesity, platelet function, and
      cardiovascular disease, we sought to examine the relationships of C-reactive
      protein (CRP) and interleukin-6 (IL-6) to the expression of key inflammatory
      transcripts in platelets. APPROACH AND RESULTS: We quantified circulating levels
      of CRP and IL-6 in 1625 participants of the Framingham Heart Study (FHS)
      Offspring cohort examination 8 (mean age, 66.6 +/- 6.6 years; 46% men). We
      measured the expression of 15 relevant genes by high-throughput quantitative
      reverse transcriptase polymerase chain reaction from platelet-derived RNA and
      used multivariable regression to relate serum concentrations of CRP and IL-6 with
      gene expression. Levels of CRP and IL-6 were associated with 10 of the 15
      platelet-derived inflammatory transcripts, ALOX5, CRP, IFIT1, IL6, PTGER2,
      S100A9, SELENBP1, TLR2, TLR4, and TNFRSF1B (P<0.001). Associations between
      platelet mRNA expression with CRP and IL-6 persisted after multivariable
      adjustment for potentially confounding factors. Six genes positively associated
      with CRP or IL-6 in the FHS sample were also upregulated in megakaryocytes in
      response to CRP or IL-6 exposure. CONCLUSIONS: Our data highlight the strong
      connection between the circulating inflammatory biomarkers CRP and IL-6 and
      platelet gene expression, adjusting for cardiovascular disease risk factors. Our
      results also suggest that body weight may directly influence these associations.

PMID- 23968980
TI  - Capillary endothelial fatty acid binding proteins 4 and 5 play a critical role in
      fatty acid uptake in heart and skeletal muscle.
AB  - OBJECTIVE: Fatty acids (FAs) are the major substrate for energy production in the
      heart. Here, we hypothesize that capillary endothelial fatty acid binding protein
      4 (FABP4) and FABP5 play an important role in providing sufficient FAs to the
      myocardium. APPROACH AND RESULTS: Both FABP4/5 were abundantly expressed in
      capillary endothelium in the heart and skeletal muscle. The uptake of a FA
      analogue, 125I-15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid, was
      significantly reduced in these tissues in double-knockout (DKO) mice for FABP4/5
      compared with wild-type mice. In contrast, the uptake of a glucose analogue, 18F
      fluorodeoxyglucose, was remarkably increased in DKO mice. The expression of
      transcripts for the oxidative catabolism of FAs was reduced during fasting,
      whereas transcripts for the glycolytic pathway were not altered in DKO hearts.
      Notably, metabolome analysis revealed that phosphocreatine and ADP levels were
      significantly lower in DKO hearts, whereas ATP content was kept at a normal
      level. The protein expression levels of the glucose transporter Glut4 and the
      phosphorylated form of phosphofructokinase-2 were increased in DKO hearts,
      whereas the phosphorylation of insulin receptor-beta and Akt was comparable
      between wild-type and DKO hearts during fasting, suggesting that a dramatic
      increase in glucose usage during fasting is insulin independent and is at least
      partly attributed to the post-transcriptional and allosteric regulation of key
      proteins that regulate glucose uptake and glycolysis. CONCLUSIONS: Capillary
      endothelial FABP4/5 are required for FA transport into FA-consuming tissues that
      include the heart. These findings identify FABP4/5 as promising targets for
      controlling the metabolism of energy substrates in FA-consuming organs that have
      muscle-type continuous capillary.

PMID- 23968982
TI  - Characterization of cardiovascular involvement in pseudoxanthoma elasticum
      families.
AB  - OBJECTIVE: Pseudoxanthoma elasticum (PXE) is an autosomal recessive connective
      tissue disorder with involvement of the skin, the retina, and the cardiovascular
      system. Cardiovascular involvement is mainly characterized by mineralization and
      fragmentation of elastic fibers of blood vessels and premature atherosclerosis.
      We conducted an ultrasound study to investigate the cardiovascular phenotype and
      to propose recommendations for the management of patients with PXE and
      heterozygous ABCC6 mutation carriers. APPROACH AND RESULTS: Thirty-two patients,
      23 carriers, and 28 healthy volunteers underwent cardiac and vascular ultrasound
      studies. Cardiac imaging revealed left ventricular diastolic dysfunction in
      patients with PXE with a significantly prolonged deceleration time and lower
      septal early diastolic velocities of the mitral annulus compared with controls.
      Carriers also demonstrated significantly prolonged deceleration time. Carotid-to
      femoral pulse wave velocity was significantly increased in patients with PXE when
      compared with carriers and controls. Vascular imaging revealed a high prevalence
      of peripheral artery disease in both patients and carriers and a significantly
      higher carotid intima-media thickness compared with controls. CONCLUSIONS: The
      results of this study clearly demonstrate impaired left ventricular diastolic
      function, impairment of the elastic properties of the aorta, and a high
      prevalence of peripheral artery disease in patients with PXE. Carriers also seem
      to exhibit a cardiovascular phenotype with mainly mild diastolic dysfunction and
      accelerated atherosclerosis. Increased awareness for cardiovascular events in
      both patients and heterozygous carriers is warranted.

PMID- 23968981
TI  - The role of shear-induced transforming growth factor-beta signaling in the
      endothelium.
AB  - OBJECTIVE: Vascular endothelial cells (ECs) are continuously exposed to blood
      flow that contributes to the maintenance of vessel structure and function;
      however, the effect of hemodynamic forces on transforming growth factor-beta (TGF
      beta) signaling in the endothelium is poorly described. We examined the potential
      role of TGF-beta signaling in mediating the protective effects of shear stress on
      ECs. APPROACH AND RESULTS: Human umbilical vein ECs (HUVECs) exposed to shear
      stress were compared with cells grown under static conditions. Signaling through
      the TGF-beta receptor ALK5 was inhibited with SB525334. Cells were examined for
      morphological changes and harvested for analysis by real-time polymerase chain
      reaction, Western blot analysis, apoptosis, proliferation, and
      immunocytochemistry. Shear stress resulted in ALK5-dependent alignment of HUVECs
      as well as attenuation of apoptosis and proliferation compared with static
      controls. Shear stress led to an ALK5-dependent increase in TGF-beta3 and Kruppel
      like factor 2, phosphorylation of endothelial NO synthase, and NO release.
      Addition of the NO donor S-nitroso-N-acetylpenicillamine rescued the cells from
      apoptosis attributable to ALK5 inhibition under shear stress. Knockdown of TGF
      beta3, but not TGF-beta1, disrupted the HUVEC monolayer and prevented the
      induction of Kruppel-like factor 2 by shear. CONCLUSIONS: Shear stress of HUVECs
      induces TGF-beta3 signaling and subsequent activation of Kruppel-like factor 2
      and NO, and represents a novel role for TGF-beta3 in the maintenance of HUVEC
      homeostasis in a hemodynamic environment.

PMID- 23968983
TI  - Protection by face masks against influenza A(H1N1)pdm09 virus on trans-Pacific
      passenger aircraft, 2009.
AB  - In response to several influenza A(H1N1)pdm09 infections that developed in
      passengers after they traveled on the same 2 flights from New York, New York,
      USA, to Hong Kong, China, to Fuzhou, China, we assessed transmission of influenza
      A(H1N1)pdm09 virus on these flights. We defined a case of infection as onset of
      fever and respiratory symptoms and detection of virus by PCR in a passenger or
      crew member of either flight. Illness developed only in passengers who traveled
      on the New York to Hong Kong flight. We compared exposures of 9 case-passengers
      with those of 32 asymptomatic control-passengers. None of the 9 case-passengers,
      compared with 47% (15/32) of control-passengers, wore a face mask for the entire
      flight (odds ratio 0, 95% CI 0-0.71). The source case-passenger was not
      identified. Wearing a face mask was a protective factor against influenza
      infection. We recommend a more comprehensive intervention study to accurately
      estimate this effect.

PMID- 23968984
TI  - Early clinical phenotypes, clinical staging, and strategic biomarker research:
      building blocks for personalized psychiatry.

PMID- 23968985
TI  - Diving deep into white matter to improve our understanding of the pathophysiology
      of schizophrenia.

PMID- 23968986
TI  - Lost their ways?

PMID- 23968987
TI  - Association of HLA-DR/DQ polymorphism with chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP) in Tunisian patients.
AB  - BACKGROUND AND OBJECTIVE: Chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP) is an immune-mediated disorder of the peripheral
      nervous system (PNS). The aim of this study was to investigate associations
      between HLA-DR/DQ alleles and CIDP in Tunisian patients. PATIENTS AND METHODS:
      HLA DR/DQ genotyping was performed using polymerase chain reaction sequence
      specific primers (PCR-SSP) with 36 CIDP patients and 100 healthy individuals
      serving as the control group. RESULTS: CIDP in Tunisian patients was found to be
      associated with the HLA-DRB1*13 allele (pc=0.03) (where pc denotes the Bonferroni
      corrected probability value). Moreover, the two haplotypes, DRB1*13/DQB1*06
      (22.22% of patients vs. 8.5% of controls, pc=0.017) and DRB1*07/DQB1*03 (13.88%
      of patients vs. 3% of controls, pc=0.005), were found to confer a susceptibility
      to CIDP. CONCLUSION: To our knowledge, this is the first study performed to
      analyze the association of HLA-DRB1/DQB1 alleles on CIDP susceptibility in a
      Tunisian population.

PMID- 23968988
TI  - The Familial Tasmanian Haematological Malignancies Study (FaTHMS): its origins,
      its history and the phenomenon of anticipation.
AB  - We began epidemiological studies of haematological malignancies (lymphomas,
      leukaemias and related diseases) in Tasmania, the island state of Australia, in
      1972. Our work has identified a number of families each containing several cases.
      In contrast to reports from elsewhere, we recognised familial cases incorporating
      the range of haematological malignancies, that is, not confined to a single
      diagnosis. Furthermore the average number of cases per extended family tree has
      exceeded that of any prior report. An unexpected discovery from the detailed
      familial analysis was that of anticipation, the phenomenon whereby the symptoms
      of a disorder become apparent at an earlier age as it is passed on to the next
      generation. These findings strengthen the case for there being genetic anomalies
      underlying the development of haematological malignancies at least in some cases,
      and are the subject of ongoing research. 

PMID- 23968989
TI  - Biogeochemical classification of South Florida's estuarine and coastal waters.
AB  - South Florida's watersheds have endured a century of urban and agricultural
      development and disruption of their hydrology. Spatial characterization of South
      Florida's estuarine and coastal waters is important to Everglades' restoration
      programs. We applied Factor Analysis and Hierarchical Clustering of water quality
      data in tandem to characterize and spatially subdivide South Florida's coastal
      and estuarine waters. Segmentation rendered forty-four biogeochemically distinct
      water bodies whose spatial distribution is closely linked to geomorphology,
      circulation, benthic community pattern, and to water management. This
      segmentation has been adopted with minor changes by federal and state
      environmental agencies to derive numeric nutrient criteria. 

PMID- 23968990
TI  - The 10-tenets for integrated, successful and sustainable marine management.

PMID- 23968991
TI  - Glophymed: an index to establish the ecological status for the Water Framework
      Directive based on phytoplankton in coastal waters.
AB  - Phytoplankton and its attributes (biomass, abundance, composition, and frequency
      and intensity of phytoplankton blooms) are essential to establish the ecological
      status in the Water Frame Directive. The aim of this study is to develop an index
      "Glophymed" based on all phytoplankton attributes for coastal water bodies
      according to the directive requirements. It is also developed an anthropogenic
      pressure index that takes into account population density, tourism, urbanization,
      industry, agriculture, fisheries and maritime transport for Comunitat Valenciana
      (Spain). Both indexes (Glophymed and human pressure index) based on a
      multisampling dataset collected monthly during several years, show a significant
      statistical correlation (r2 0.75 alpha<0.01) for typology IIA and (r2 0.93
      alpha<0.01) for typology III-W. The relation between these indexes provides
      suitable information about the integrated management plans and protection
      measures of water resources since the Glophymed index is very sensitive to human
      pressures. 

PMID- 23968992
TI  - Ocean in peril: reforming the management of global ocean living resources in
      areas beyond national jurisdiction.
AB  - This article presents the outcome of research aimed at assisting governments in
      meeting their commitments and legal obligations for sustainable fisheries, based
      on increasing evidence that global fisheries are in crisis. The article assesses
      the effectiveness of the existing legal and institutional framework for high seas
      living resources. It focuses on: (1) the role of regional fisheries management
      organizations (RFMOs); (2) tools for compliance and enforcement to stem illegal
      fishing; and (3) mechanisms for habitat protection. The article further
      highlights a variety of options for addressing key weaknesses and gaps in current
      ocean governance, including United Nations General Assembly (UNGA) resolutions,
      reforms at the regional level, as well as a possible new legal instrument, with a
      view to informing international discussions on ways to ensure the sustainable use
      of high seas resources without compromising the health of the marine environment.

PMID- 23968993
TI  - Multifaceted roles of ultra-rare and rare disease patients/parents in drug
      discovery.
AB  - Individual parents and patients are increasingly doing more to fund, discover and
      develop treatments for rare and ultra-rare diseases that afflict their children,
      themselves or their friends. They are performing roles in business development
      that would be classed as entrepreneurial; and their organizational roles in
      driving the science in some cases are equivalent to those of principal
      investigators. These roles are in addition to their usual positioning as
      advocates. Through their efforts and those of the collaborative networks that
      they have developed, they could be positioned to disrupt the usual course of drug
      discovery. This can be illustrated using three different ultra-rare disease
      parent/patient advocate groups and the diseases for which they are developing
      treatments. This represents an alternative model for pharmaceutical research. 

PMID- 23968994
TI  - A fluorescent spectroscopy and modelling analysis of anti-heparanase aptamers
      serum protein interactions.
AB  - Aptamers are short, single stranded oligonucleotide or peptide molecules that
      bind a specific target molecule and can be used for the delivery of therapeutic
      agents and/or for imaging and clinical diagnosis. Several works have been
      developed aiming at the production of aptamers and the study of their
      applications, but few results have been reported on plasmatic dynamics of such
      products. Aptamers against the heparanase enzyme have been previously described.
      In this work, the interactions of two constructs of the most promising anti
      heparanase aptamer (molecular weights about 9200Da and 22000Da) to human and
      bovine serum albumins were studied by fluorescence quenching technique. Stern
      Volmer graphs were plotted and quenching constants were estimated. Stern-Volmer
      plots obtained from experiments carried out at 25 degrees C and 37 degrees C
      showed that the quenching of fluorescence of HSA and BSA by the low molecular
      weight aptamer was a collisional phenomenon (estimated Stern-Volmer constant:
      3.22 (+/-0.01)*10(5)M(-1) for HSA at 37 degrees C and 2.47 (+/-0.01)*10(5)M(-1)
      for HSA at 25 degrees C), while the high molecular weight aptamer quenched
      albumins by static process (estimated Stern-Volmer constant: 4.05 (+/
      0.01)*10(5)M(-1) for HSA at 37 degrees C and 6.20 (+/-0.01)*10(5)M(-1) for HSA at
      25 degrees C), interacting with those proteins constituting complexes. Linear
      Stern-Volmer plot from HSA titrated with the low MW aptamer suggested the
      existence of a single binding site for the quencher in this albumin. Differently,
      for aptamer 2, the slightly downward curvature of the Stern-Volmer plot of the
      titration for that albumin suggested a possible conformational change that led to
      the exposition of lower affinity binding sites in HSA at 25 degrees C. Similarly,
      although short aptamerdoes not appear to form a stable complex (collisional
      interaction), the longer aptamer is found to form a stable complex with HSA. In
      addition, the behaviour of quenching curves for HSA and BSA and values estimated
      for ratio R1/R2 from model developed by Silva et al. suggest that the primary
      binding site in both aptamers is located closer to the tryptophan residue in sub
      domain IIA. It is likely that both aptamers are competing for the same primary
      site in albumin. 

PMID- 23968995
TI  - Multispectroscopic methods reveal different modes of interaction of anti cancer
      drug mitoxantrone with Poly(dG-dC).Poly(dG-dC) and Poly(dA-dT).Poly(dA-dT).
AB  - The interaction of mitoxantrone with alternating Poly(dG-dC).Poly(dG-dC) and
      Poly(dA-dT).Poly(dA-dT) duplex has been studied by absorption, fluorescence and
      Circular Dichroism (CD) spectroscopy at Drug to Phosphate base pair ratios
      D/P=20.0-0.04. Binding to GC polymer occurs in two distinct modes: partial
      stacking characterized by red shifts of 18-23nm at D/P=0.2-0.8 and external
      binding at D/P=1.0-20.0 whereas that to AT polymer occurs externally in the
      entire range of D/P. The binding constant and number of binding sites is
      3.7*10(5)M(-1), 0.3 and 1.3* 10(4)M(-1), 1.5 in GC and AT polymers, respectively
      at low D/P ratios. CD binding isotherms show breakpoints at D/P=0.1, 0.5 and
      0.25, 0.5 in GC and AT polymers, respectively. The intrinsic CD bands indicate
      that the distortions in GC polymer are significantly higher than that in AT
      polymer. Docking studies show partial insertion of mitoxantrone rings between to
      GC base pairs in alternating GC polymer. Side chains of mitoxantrone interact
      specifically with base pairs and DNA backbone. The studies are relevant to the
      understanding of suppression or inhibition of DNA cleavage on formation of
      ternary complex with topoisomerase-II enzyme and hence the anti cancer action. 

PMID- 23968996
TI  - Analysis of chlorophyll fluorescence spectra for the monitoring of Cd toxicity in
      a bio-energy crop (Jatropha curcas).
AB  - The vegetation of metal-contaminated soils using non-edible crops can be a safe
      and economical technique for Cd immobilization and the remediation of
      contaminated sites. Jatropha (Jatropha curcas L.) exhibits a relative tolerance
      to heavy metals and potential for biofuel production. The study was performed to
      monitor the Cd-induced alterations in jatropha plants by X-ray chlorophyll
      fluorescence. The Cd effects on photosynthetic pigments, the mineral composition
      of plants, defense enzyme activity and soluble proteins were also studied. Plants
      were grown for 20days in a nutrient solution with five Cd contents: 5, 10, 20, 30
      and 40MUmolL(-1); a control with no Cd addition was also monitored. The analysis
      of the chlorophyll fluorescence spectra allowed detecting alterations caused by
      Cd toxicity in the jatropha plants. The mineral composition of the plants was
      affected by the Cd doses; however, the Fe and Mg contents were not significantly
      reduced, which most likely improved the effects on the contents of the
      photosynthetic pigments. Because of its relative tolerance to Cd, Jatropha curcas
      may be a promising species to revegetate Cd-contaminated sites. Considering the
      long period needed to phytoremediate soils, the combination of remediation with
      bioenergy production could be an attractive option. 

PMID- 23968997
TI  - Pain control following total knee replacement surgery.

PMID- 23968998
TI  - The emergent discipline of health web science.
AB  - The transformative power of the Internet on all aspects of daily life, including
      health care, has been widely recognized both in the scientific literature and in
      public discourse. Viewed through the various lenses of diverse academic
      disciplines, these transformations reveal opportunities realized, the promise of
      future advances, and even potential problems created by the penetration of the
      World Wide Web for both individuals and for society at large. Discussions about
      the clinical and health research implications of the widespread adoption of
      information technologies, including the Internet, have been subsumed under the
      disciplinary label of Medicine 2.0. More recently, however, multi-disciplinary
      research has emerged that is focused on the achievement and promise of the Web
      itself, as it relates to healthcare issues. In this paper, we explore and
      interrogate the contributions of the burgeoning field of Web Science in relation
      to health maintenance, health care, and health policy. From this, we introduce
      Health Web Science as a subdiscipline of Web Science, distinct from but
      overlapping with Medicine 2.0. This paper builds on the presentations and
      subsequent interdisciplinary dialogue that developed among Web-oriented
      investigators present at the 2012 Medicine 2.0 Conference in Boston,
      Massachusetts. 

PMID- 23968999
TI  - Doppler ultrasonographic assessment of uterine arteries during normal canine
      puerperium.
AB  - The aim of this study was to describe Doppler ultrasonographic changes of uterine
      arteries during normal canine puerperium. Eight healthy, pure-bred bitches, were
      ultrasonographically assessed during the postpartum period on Days -3, 3, 10, 17,
      24, 38, 52 and 80 (Day 0 defined as the day of parturition). Total horn diameters
      (TD) and endometrium thickness (E) were evaluated. Color Doppler was used to
      localize uterine arteries at both sides of the body and pulsed-wave Doppler was
      performed to obtain the waveforms. Peak systolic velocity (PSV) and end diastolic
      velocity (EDV) were measured. Resistance index [(PSV-EDV)/PSV] was automatically
      calculated. Values of TD, E, PSV, EDV and RI were analyzed by repeated measures
      ANOVA followed by LSD test (SPSS 18.0; SPSS, Chicago, IL, USA). A correlation
      analysis was also carried out between RI and TD. A progressive decrease of TD
      (P<0.01) and E (P<0.01) was found in the course of the study. A gradual
      diminution of PSV (P<0.01) and EDV (P<0.01) and an increase of RI (P<0.01) were
      also found throughout the study period. The resistance index negatively
      correlated with TD (r=-0.46; P<0.01) and E (r=-0.44; P<0.01) while the
      ultrasonographic and vascular changes in this period are concurrent with
      regenerative changes in the glandular and epithelial structures of the uterus. It
      is concluded that uterine artery RI progressively increased during normal canine
      puerperium, associated to the two-dimensional ultrasonographic regression of the
      organ. 

PMID- 23969001
TI  - Validation of Toxtree and SciQSAR in silico predictive software using a publicly
      available benchmark mutagenicity database and their applicability for the
      qualification of impurities in pharmaceuticals.
AB  - The draft ICH M7 guidance (US FDA, 2013) recommends that the computational
      assessment of bacterial mutagenicity for the qualification of impurities in
      pharmaceuticals be performed using an expert rule-based method and a second
      statistically-based (Q)SAR method. The public nonproprietary 6489 compound Hansen
      benchmark mutagenicity data set was used as an external validation data set for
      Toxtree, a free expert rule-based SAR software. This is the largest known
      external validation of Toxtree. The Toxtree external validation specificity,
      sensitivity, concordance and false negative rate for this mutagenicity data set
      was 66%, 80%, 74% and 20%, respectively. This mutagenicity data set was also used
      to create a statistically-based SciQSAR-Hansen mutagenicity model. In a 10% leave
      group-out internal cross validation study the specificity, sensitivity,
      concordance and false negative rate for the SciQSAR mutagenicity model was 71%,
      83%, 77% and 17%, respectively. Combining Toxtree and SciQSAR predictions and
      scoring a positive finding in either software as a positive mutagenicity finding
      reduced the false negative rate to 7% and increased sensitivity to 93% at the
      expense of specificity which decreased to 53%. The results of this study support
      the applicability of Toxtree, and the SciQSAR-Hansen mutagenicity model for the
      qualification of impurities in pharmaceuticals. 

PMID- 23969002
TI  - We've had important advances in the connexin/pannexin field, yet there is still
      much to do.

PMID- 23969000
TI  - Neural processing correlates of assaultive violence exposure and PTSD symptoms
      during implicit threat processing: a network-level analysis among adolescent
      girls.
AB  - Assaultive violence exposure during childhood is a significant risk factor for
      posttraumatic stress disorder (PTSD). The purpose of the present study was to
      characterize the relationships of assault and PTSD severity with the organization
      of large-scale networks identified during emotion processing. Adolescent girls
      aged 12-16 with (N=15) and without (N=15) histories of assault underwent
      functional magnetic resonance imaging (fMRI) while engaged in a task that
      presented images of fearful or neutral facial expressions. Independent component
      analysis (ICA) identified a frontocingulate network, a frontoparietal network,
      and a default mode network. Assault exposure was associated with significantly
      greater activation of the frontocingulate network for fear versus neutral faces.
      Within the frontocingulate network, Posttraumatic stress disorder (PTSD) severity
      was associated with weakened functional connectivity between the left amygdala
      and the perigenual anterior cingulate. Within the frontoparietal network,
      assaulted girls demonstrated weakened connectivity of the premotor cortex with
      the right middle frontal gyrus. Within the default mode network, assault exposure
      and PTSD severity were associated with strengthening functional connectivity of
      the parahippocampus with the medial and lateral prefrontal cortex, respectively.
      Individual differences in functional connections within the frontocingulate
      network and frontoparietal network among the assaulted group were strongly
      associated with caregiver-rated family disengagement. These results demonstrate
      associations between assault and PTSD symptoms with the functional organization
      of large-scale frontoparietal, frontocingulate, and default mode networks during
      emotion processing. The relationship with caregiver-rated family disengagement
      suggests the impact of family support on the neural processing correlates of
      assault and PTSD symptoms. 

PMID- 23969003
TI  - Paroxysmal ataxia and dysarthria in multiple sclerosis.
AB  - Paroxysmal ataxia and dysarthria are part of the spectrum of transient
      neurological disturbances that can be frequently encountered in multiple
      sclerosis (MS). Prompt recognition of these symptoms is important because they
      can be the only manifestation of a MS relapse and symptomatic therapy is often
      beneficial. We report a patient who developed paroxysmal ataxia and dysarthria,
      documented by video imaging, while he was recovering from a MS relapse. Treatment
      with carbamazepine resulted in the complete reversal of the paroxysmal ataxia and
      dysarthria. 

PMID- 23969004
TI  - Anterior pseudoarthrectomy for symptomatic Bertolotti's syndrome.
AB  - Painful L5/S1 pseudoarthrosis has been previously managed with posterior excision
      and/or lumbar fusion. To our knowledge, the anterior approach for L5/S1
      pseudoarthrectomy in the treatment of Bertolotti's syndrome has not been
      described. We present two patients with severe symptomatic L5/S1 pseudoarthroses
      that were successfully excised via an anterior retroperitoneal approach with 2
      year clinical and radiological follow-up. The literature regarding surgical
      treatments for Bertolotti's syndrome is reviewed. The technique for an anterior
      retroperitoneal approach is described. This approach has been safe and effective
      in providing long term symptomatic relief to our two patients. Further studies
      comparing the outcomes of anterior versus posterior pseudoarthrectomy will guide
      the management of this condition.

PMID- 23969006
TI  - EGFR exon 20 insertion A763-Y764insFQEA and response to erlotinib--Letter.

PMID- 23969007
TI  - Cardiogenic shock following electro-cardioversion of new onset atrial flutter.
AB  - Transient hypotension and atrial stunning are known complications of electro
      cardioversion for supra-ventricular tachyarrhythmias, however, a clinically
      significant cardiac failure is extremely rare in this setting. We, herein,
      present a 77-year-old African American male who underwent electro-cardioversion
      following an unremarkable transesophageal echocardiogram (TEE) for a symptomatic
      atrial flutter of a new onset. Immediately post-cardioversion, he suffered severe
      hypotension with a depressed LV systolic function. IV dobutamine stabilized his
      blood pressure. 

PMID- 23969005
TI  - Oxidative stress and phthalate-induced down-regulation of steroidogenesis in MA
      10 Leydig cells.
AB  - Previous studies have shown that phthalate exposure can suppress steroidogenesis.
      However, the affected components of the steroidogenic pathway, and the mechanisms
      involved, remain uncertain. We show that incubating MA-10 Leydig cells with mono
      (2-ethylhexyl) phthalate (MEHP) resulted in reductions in luteinizing hormone
      (LH)-stimulated cAMP and progesterone productions. cAMP did not decrease in
      response to MEHP when the cells were incubated with cholera toxin or forskolin.
      Incubation of MEHP-treated cells with dibutyryl-cAMP, 22-hydroxycholesterol or
      pregnenolone inhibited the reductions in progesterone. Increased levels of
      reactive oxygen species (ROS) occurred in response to MEHP. In cells in which
      intracellular glutathione was depleted by buthionine sulfoximine pretreatment,
      the increases in ROS and decreases in progesterone in response to MEHP treatment
      were exacerbated. These results indicate that MEHP inhibits MA-10 Leydig cell
      steroidogenesis by targeting LH-stimulated cAMP production and cholesterol
      transport, and that a likely mechanism by which MEHP acts is through increased
      oxidative stress. 

PMID- 23969008
TI  - Respiratory failure due to infliximab induced interstitial lung disease.
AB  - Although poorly understood, interstitial lung disease has been reported as a
      possible complication of tumor necrosis factor alpha inhibitors. We report a case
      of interstitial lung disease in a 64-year-old man with psoriasis 3 weeks after
      the initiation of infliximab treatment. The patient had received two fortnightly
      infusions of infliximab following a short course of methotrexate. Thoracic
      computed tomography showed bilateral ground glass and interstitial infiltrates,
      while the results of microbiology and immunologic workup were negative. Likewise,
      bronchoalveolar lavage detected neither typical nor atypical pathogens.
      Infliximab-induced interstitial lung injury was suspected and corticosteroid
      therapy was administered which resulted in rapid clinical and radiological
      improvement. This is one of the few reported cases of interstitial lung disease
      due to infliximab in the psoriasis population. The patient had no pre-existing
      lung pathology, while his previous exposure to methotrexate was minimal and was
      not temporally associated with the induction of interstitial lung disease.

PMID- 23969009
TI  - [Imaging and quantification of corneal neovascularization].
AB  - Corneal neovascularization is defined as the invasion of vessels into the
      normally avascular clear corneal stroma, secondary to acute or chronic tissue
      injury. In addition to decreasing visual acuity, vascularity introduces
      circulating immune cells, reducing corneal immune privilege and the graft
      survival of subsequent keratoplasty. Thus, reducing neovascularization has become
      a recent therapeutic target in order to increase the success of corneal
      transplantation. Comparing the effects of antiangiogenic drugs assumes that we
      are able to quantify corneal neovascularization before and after treatment. In
      the first part of this literature review, we present the various methods to
      document neovessels (color photos, fluorescein and indocyanine green anterior
      segment angiography, in vivo confocal microscopy). Next, we report methods to
      classify and quantify corneal neovascularization. 

PMID- 23969010
TI  - Elucidating the mechanism of Cr(VI) formation upon the interaction with metal
      oxides during coal oxy-fuel combustion.
AB  - The thermodynamics underpinning the interaction of Cr-bearing species with basic
      metal oxides, i.e. K2O, Fe2O3, MgO and CaO, during the air and oxy-fuel
      combustion of coal have been examined. The synchrotron-based X-ray adsorption
      near-edge spectroscopy (XANES) was used for Cr speciation. For the oxides tested,
      Cr(VI) formation is dominated by the reduction potential of the metals. The
      oxides of Ca(2+) with high reduction potential favored the oxidation of Cr(III),
      same for K(+). The other two basic metals, Fe2O3 and MgO with lower reduction
      potentials reacted with Cr(III) to form the corresponding chromites at the
      temperatures above 600 degrees C. Coal combustion experiments in drop-tube
      furnace have confirmed the rapid capture of Cr vapors, either trivalent or
      hexavalent, by CaO into solid ash. The existence of HCl in flue gas favored the
      vaporization of Cr as CrO2Cl2, which was in turn captured by CaO into chromate.
      Both Fe2O3 and MgO exhibited less capability on scavenging the Cr(VI) vapor.
      Particularly, MgO alone exhibited a low capability for capturing the vaporized
      Cr(III) vapors. However, its co-existence with CaO in the furnace inhibited the
      Cr(VI) formation. This is beneficial for minimizing the toxicity of Cr in the
      coal combustion-derived fly ash. 

PMID- 23969011
TI  - Two-dimensional surface plasmon resonance imager: An approach to study neuronal
      differentiation.
AB  - There is a growing demand for the development of a new bioanalytical technique
      that is capable of monitoring neuronal differentiation noninvasively, in real
      time, and without any fluorescent probes. In a previous article, we demonstrated
      that a high-resolution two-dimensional surface plasmon resonance (2D-SPR) imager
      was very useful to monitor cell response on chemical stimulation in which protein
      kinase C (PKC) translocation was related. In the current study, we focused on
      developing a new method for monitoring neuronal differentiation and examined the
      application of the high-resolution 2D-SPR imager to monitor neuronal
      differentiation noninvasively and by a label-free format. We successfully
      monitored the intracellular signal transduction, which was mainly translocation
      of PKC in PC12 cells by the 2D-SPR imager, and found that the cells treated with
      a differentiation factor, nerve growth factor (NGF), showed a remarkable
      enhancement of 2D-SPR response to muscarine, carbachol, and acetylcholine
      stimulation. The results demonstrated that 2D-SPR sensing is applicable to in
      situ assessment of neuronal differentiation and to studying the expression state
      of the specific receptors in the living state.

PMID- 23969012
TI  - A semi-automated method for isolating functionally intact mitochondria from
      cultured cells and tissue biopsies.
AB  - Mitochondrial dysfunctions decisively contribute to the progression of human
      diseases, implying that functional tests of isolated mitochondria may furnish
      conclusive information for diagnosis and therapy. Classical mitochondrial
      isolation methods, however, lack precisely adjustable settings for cell rupture,
      which is the most critical step in this procedure, and this complicates
      subsequent analyses. Here, we present an efficient method to isolate functionally
      active, intact mitochondria from cultured or primary cells and minute tissue
      samples in a rapid, highly reproducible manner.

PMID- 23969013
TI  - Modified S/MAR episomal vectors for stably expressing fluorescent protein-tagged
      transgenes with small cell-to-cell fluctuations.
AB  - We modified and tested scaffold/matrix attachment region (S/MAR) episomal
      vectors. The new vectors would be useful in obtaining cells stably expressing
      fluorescent protein-tagged transgenes with small, mostly within 10-fold cell-to
      cell fluctuations. In the vectors, the same transcript directs episomal
      replication and expression of transgene/antibiotic marker, and only antibiotic
      selection without any other extra steps was sufficient to obtain desired stable
      cells, including those expressing two different proteins simultaneously.
      Furthermore, the two test cases (expression of human growth hormone in AtT20 and
      four protein kinase C isoforms in HEK293) would prove to be useful in visualizing
      and analyzing regulatory processes involving these proteins.

PMID- 23969014
TI  - Enhancement of ovarian tumor classification by improved reproducibility in matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry of serum
      glycans.
AB  - The serum N-glycome is a promising source of biomarker discovery. Matrix-assisted
      laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS)
      profiling of serum N-glycans was attempted for differentiating borderline ovarian
      tumor from benign cases, for which a low data spread is essential. An
      experimental protocol using matrix-prespotted MALDI plates and fast vacuum drying
      of the loaded N-glycan samples was developed, thereby minimizing the intensity
      variations in the replicates to an average relative standard deviation (RSD) of
      3.96% for the highest N-glycan peak (m/z 1485.53) of the Sigma-Aldrich serum
      standard. When applied to sera of ovarian tumors, this procedure exhibited an
      average RSD of 5.74% for m/z 1485.53 and of 7.28% for all MS peaks. This improved
      reproducibility combined with the OVA-Beyond((r)) screening software resulted in
      75.1% and 79.4% correct classification for benign and borderline tumor samples,
      respectively, while the classification rates by the conventional ovarian tumor
      marker CA-125 were 54.4% and 53.1%, respectively. Both true positive rate and
      true negative rate fluctuated with small numbers of markers and converged as the
      number of markers increased. Cross-validations were performed in comparison with
      CA-125. These results suggest that our optimized process for MALDI-TOF MS of the
      serum glycome has a great potential for the screening of early stage ovarian
      cancer.

PMID- 23969015
TI  - gamma-Cyclodextrin-polyurethane copolymer adsorbent for selective removal of
      endotoxin from DNA solution.
AB  - Copolymer particles for removal of endotoxins (lipopolysaccharides, LPSs) were
      prepared by suspension copolymerization of gamma-cyclodextrin (CyD) and 1,6
      hexamethylenediisocyanate. The LPS-removing activity of the copolymer particles
      was compared with that of poly(epsilon-lysine)-immobilized Cellufine (cationic
      adsorbent) or polystyrene particles (hydrophobic adsorbent) by a batch method.
      When DNA was present in solution with LPSs under physiological conditions (pH
      6.0, ionic strength of MU = 0.05-0.8), LPS-removing activity of the cationic or
      hydrophobic adsorbent was unsatisfactory because both the DNA and the LPSs were
      adsorbed onto each adsorbent. By contrast, the copolymer particles with gamma-CyD
      cavity (CyD content: 14-20 mol%) could selectively remove LPSs from a DNA
      solution (50 MUg ml(-1), pH 6.0, and MU = 0.05-0.2) containing LPSs (15 EU ml(
      1)) without the adsorption of DNA. The residual concentration of LPSs in the
      treated DNA solution was below 0.1 EU ml(-1), and the recovery of DNA was 99%.

PMID- 23969016
TI  - Re: Current practice in paediatric hypospadias surgery: specialist survey.

PMID- 23969017
TI  - Powassan meningoencephalitis, New York, New York, USA.
AB  - Disease caused by Powassan virus (POWV), a tick-borne flavivirus, ranges from
      asymptomatic to severe neurologic compromise and death. Two cases of POWV
      meningoencephalitis in New York, USA, highlight diagnostic techniques, neurologic
      outcomes, and the effect of POWV on communities to which it is endemic.

PMID- 23969018
TI  - Urinary adiponectin excretion rises with increasing albuminuria in type 1
      diabetes.
AB  - AIM: Urinary adiponectin (u-adiponectin) excretion has been suggested to reflect
      early glomerular damage. Inspired by this, we studied the levels of u-adiponectin
      in type 1 diabetic patients with different levels of urinary albumin excretion
      (UAE). METHODS: U-adiponectin was analysed by ELISA in type 1 diabetic patients:
      Fifty-eight with normoalbuminuria (<30mg albumin/24h), 43 with persistent
      microalbuminuria (30-300mg/24h) and 44 with persistent macroalbuminuria
      (>300mg/24h). For comparison, a control group of 55 healthy individuals was
      included. RESULTS: U-adiponectin increased with increasing levels of UAE
      (p<0.01). U-adiponectin median (interquartile range): Normoalbuminuria 0.38 (0.14
      1.31), microalbuminuria 1.12 (0.20-2.68), macroalbuminuria 9.20 (1.10-23.35) and
      controls 0.09 (0.06-0.24) MUg/g creatinine. Levels were unrelated to sex, age,
      cholesterol, diastolic BP and BMI. U-adiponectin was weakly associated with
      increasing systolic BP and HbA1c (r(2)<0.1, p<0.05), but strongly related to
      increasing UAE (r(2)=0.57, p<0.001) and decreasing eGFR (r(2)=0.26, p<0.001). The
      relationship between UAE and u-adiponectin was significant in all groups and
      independent of eGFR, BMI, BP and HbA1c. Furthermore, u-adiponectin was associated
      with markers of tubular damage (p<0.01). CONCLUSION: U-adiponectin rises with
      increasing levels of UAE in patients with type 1 diabetes. This is in accordance
      with the hypothesis that loss of adiponectin may reflect glomerular and/or
      tubular damage.

PMID- 23969019
TI  - Paraneoplastic and non-paraneoplastic retinopathy and optic neuropathy:
      evaluation and management.
AB  - Paraneoplastic syndromes involving the visual system are a heterogeneous group of
      disorders occurring in the setting of systemic malignancy. Timely recognition of
      one of these entities can facilitate early detection and treatment of an
      unsuspected, underlying malignancy, sometimes months before it would have
      otherwise presented, and gives the patient an increased chance at survival. We
      outline the clinical features, pathogenesis, and treatment strategies for the
      retinal- and optic nerve-based paraneoplastic syndromes: cancer-associated
      retinopathy; melanoma-associated retinopathy; paraneoplastic vitelliform
      maculopathy; bilateral diffuse uveal melanocytic proliferation; paraneoplastic
      optic neuropathy; and polyneuropathy, organomegaly, endocrinopathy, monoclonal
      gammopathy, and skin changes syndrome. Distinguishing these disorders from their
      non-paraneoplastic counterparts (e.g., autoimmune-related retinopathy and optic
      neuropathy, and acute zonal occult outer retinopathy) and determining appropriate
      systemic evaluation for the responsible tumor can be challenging. In addition, we
      discuss the utility and interpretation of autoantibody testing.

PMID- 23969020
TI  - Medical management for the prevention and treatment of diabetic macular edema.
AB  - Recent clinical trials have changed the management paradigm for diabetic macular
      edema (DME). There is an urgent need to identify the most effective ways of
      preventing retinopathy or intervening at an early, asymptomatic stage in order to
      preserve vision. The rise in the incidence of diabetes is a serious public health
      concern. Grading and screening programmes help to identify sight threatening
      diabetic retinopathy in the community early and facilitate timely referral to an
      ophthalmologist. Systemic therapies for DME target the key modifiable risk
      factors: metabolic and blood pressure control. There may also be a role for
      modification of the renin-angiotensin system and for lipid lowering agents.
      Improved glycemic and blood pressure control remain the most effective ways of
      reducing morbidity from DME. Fenofibrate also has beneficial effects, but the
      mechanism for this remains unclear. Multiple new treatments are in the pipeline,
      and these are expected to change our approach to DME for the first time in 30
      years. 

PMID- 23969021
TI  - The epidemiology and etiology of pediatric ocular trauma.
AB  - Eighteen million people worldwide have uniocular blindness from traumatic injury.
      Injuries occur disproportionally commonly in childhood. Every year a quarter of a
      million children present with serious ocular trauma. For the vast majority the
      injury is preventable. We review the international literature that identifies
      high-risk circumstances. 

PMID- 23969022
TI  - Authors' response.

PMID- 23969023
TI  - Newborn glaucoma on the Arabian Peninsula.

PMID- 23969024
TI  - Gene regulatory elements of the cardiac conduction system.
AB  - The coordinated contraction of the heart relies on the generation and conduction
      of the electrical impulse. Aberrations of the function of the cardiac conduction
      system have been associated with various arrhythmogenic disorders and increased
      risk of sudden cardiac death. The genetics underlying conduction system function
      have been investigated using functional studies and genome-wide association
      studies. Both methods point towards the involvement of ion channel genes and the
      transcription factors that govern their activity. A large fraction of disease-
      and trait-associated sequence variants lie within non-coding sequences, enriched
      with epigenetic marks indicative of regulatory DNA. Although sequence
      conservation as a result of functional constraint has been a useful property to
      identify transcriptional enhancers, this identification process has been advanced
      through the development of techniques such as ChIP-seq and chromatin conformation
      capture technologies. The role of variation in gene regulatory elements in the
      cardiac conduction system has recently been demonstrated by studies on enhancers
      of SCN5A/SCN10A and TBX5. In both studies, a region harbouring a functionally
      implicated single-nucleotide polymorphism was shown to drive reproducible cardiac
      expression in a reporter gene assay. Furthermore, the risk variant of the allele
      abrogated enhancer function in both cases. Functional studies on regulatory DNA
      will likely receive a boost through recent developments in genome modification
      technologies. 

PMID- 23969026
TI  - Analysis of DNA structure and sequence requirements for Pseudomonas aeruginosa
      MutL endonuclease activity.
AB  - The hallmark of the mismatch repair system in bacterial and eukaryotic organisms
      devoid of MutH is the presence of a MutL homologue with endonuclease activity.
      The aim of this study was to analyse whether different DNA structures affect
      Pseudomonas aeruginosa MutL (PaMutL) endonuclease activity and to determine if a
      specific nucleotide sequence is required for this activity. Our results showed
      that PaMutL was able to nick covalently closed circular plasmids but not linear
      DNA at high ionic strengths, while the activity on linear DNA was only found
      below 60 mM salt. In addition, single strand DNA, ss/ds DNA boundaries and
      negatively supercoiling degree were not required for PaMutL nicking activity.
      Finally, the analysis of the incision sites revealed that PaMutL, as well as
      Bacillus thuringiensis MutL homologue, did not show DNA sequence specificity. 

PMID- 23969027
TI  - TRIM proteins as trim tabs for the homoeostasis.
AB  - The tripartite motif (TRIM) or RBCC proteins are characterized by the TRIM
      composed of a RING finger, B-box and coiled-coil domains. TRIM proteins often
      play roles in the post-translational protein modification, including
      ubiquitylation and other ubiquitin-like modifications. Evidence has accumulated
      in regard to the contribution of TRIM proteins to diverse cellular processes,
      including such as cell cycle progression, apoptosis, immunity and transcriptional
      regulation. In particular, some of the TRIM proteins have been characterized to
      exert oncogenic or tumour suppressor-like functions depending on the context. A
      recent report by Inoue and his colleagues has revealed that Terf/TRIM17
      stimulates the degradation of a kinetochore protein ZWINT and regulates the
      proliferation of breast cancer cells. Terf has also been paid attention as a
      factor promoting neuronal apoptosis, by degrading a Bcl2-like anti-apoptotic
      protein Mcl-1. Like aircraft trim tabs, TRIM proteins trim the balance of
      homoeostasis by modulating various biological pathways through protein-protein
      interactions. 

PMID- 23969025
TI  - ITPA (inosine triphosphate pyrophosphatase): from surveillance of nucleotide
      pools to human disease and pharmacogenetics.
AB  - Cellular nucleotide pools are often contaminated by base analog nucleotides which
      interfere with a plethora of biological reactions, from DNA and RNA synthesis to
      cellular signaling. An evolutionarily conserved inosine triphosphate
      pyrophosphatase (ITPA) removes the non-canonical purine (d)NTPs inosine
      triphosphate and xanthosine triphosphate by hydrolyzing them into their
      monophosphate form and pyrophosphate. Mutations in the ITPA orthologs in model
      organisms lead to genetic instability and, in mice, to severe developmental
      anomalies. In humans there is genetic polymorphism in ITPA. One allele leads to a
      proline to threonine substitution at amino acid 32 and causes varying degrees of
      ITPA deficiency in tissues and plays a role in patients' response to drugs.
      Structural analysis of this mutant protein reveals that the protein is
      destabilized by the formation of a cavity in its hydrophobic core. The Pro32Thr
      allele is thought to cause the observed dominant negative effect because the
      resulting active enzyme monomer targets both homo- and heterodimers to
      degradation. 

PMID- 23969028
TI  - Linear ubiquitination-mediated NF-kappaB regulation and its related disorders.
AB  - Ubiquitination is a post-translational modification involved in the regulation of
      a broad variety of cellular functions, such as protein degradation and signal
      transduction, including nuclear factor-kappaB (NF-kappaB) signalling. NF-kappaB
      is crucial for inflammatory and immune responses, and aberrant NF-kappaB
      signalling is implicated in multiple disorders. We found that linear ubiquitin
      chain assembly complex (LUBAC), composed of HOIL-1L, HOIP and SHARPIN, generates
      a novel type of Met1 (M1)-linked linear polyubiquitin chain and specifically
      regulates the canonical NF-kappaB pathway. Moreover, specific deubiquitinases,
      such as CYLD, A20 (TNFAIP3) and OTULIN/gumby, inhibit LUBAC-induced NF-kappaB
      activation by different molecular mechanisms, and several M1-linked ubiquitin
      specific binding domains have been structurally defined. LUBAC and these linear
      ubiquitination-regulating factors contribute to immune and inflammatory processes
      and apoptosis. Functional impairments of these factors are correlated with
      multiple disorders, including autoinflammation, immunodeficiencies, dermatitis, B
      cell lymphomas and Parkinson's disease. This review summarizes the molecular
      basis and the pathophysiological implications of the linear ubiquitination
      mediated NF-kappaB activation pathway regulation by LUBAC. 

PMID- 23969029
TI  - Pedometer-based internet-mediated intervention for adults with chronic low back
      pain: randomized controlled trial.
AB  - BACKGROUND: Chronic pain, especially back pain, is a prevalent condition that is
      associated with disability, poor health status, anxiety and depression, decreased
      quality of life, and increased health services use and costs. Current evidence
      suggests that exercise is an effective strategy for managing chronic pain.
      However, there are few clinical programs that use generally available tools and a
      relatively low-cost approach to help patients with chronic back pain initiate and
      maintain an exercise program. OBJECTIVE: The objective of the study was to
      determine whether a pedometer-based, Internet-mediated intervention can reduce
      chronic back pain-related disability. METHODS: A parallel group randomized
      controlled trial was conducted with 1:1 allocation to the intervention or usual
      care group. 229 veterans with nonspecific chronic back pain were recruited from
      one Department of Veterans Affairs (VA) health care system. Participants
      randomized to the intervention received an uploading pedometer and had access to
      a website that provided automated walking goals, feedback, motivational messages,
      and social support through an e-community (n=111). Usual care participants
      (n=118) also received the uploading pedometer but did not receive the automated
      feedback or have access to the website. The primary outcome was measured using
      the Roland Morris Disability Questionnaire (RDQ) at 6 months (secondary) and 12
      months (primary) with a difference in mean scores of at least 2 considered
      clinically meaningful. Both a complete case and all case analysis, using linear
      mixed effects models, were conducted to assess differences between study groups
      at both time points. RESULTS: Baseline mean RDQ scores were greater than 9 in
      both groups. Primary outcome data were provided by approximately 90% of
      intervention and usual care participants at both 6 and 12 months. At 6 months,
      average RDQ scores were 7.2 for intervention participants compared to 9.2 for
      usual care, an adjusted difference of 1.6 (95% CI 0.3-2.8, P=.02) for the
      complete case analysis and 1.2 (95% CI -0.09 to 2.5, P=.07) for the all case
      analysis. A post hoc analysis of patients with baseline RDQ scores >=4 revealed
      even larger adjusted differences between groups at 6 months but at 12 months the
      differences were no longer statistically significant. CONCLUSIONS: Intervention
      participants, compared with those receiving usual care, reported a greater
      decrease in back pain-related disability in the 6 months following study
      enrollment. Between-group differences were especially prominent for patients
      reporting greater baseline levels of disability but did not persist over 12
      months. Primarily, automated interventions may be an efficient way to assist
      patients with managing chronic back pain; additional support may be needed to
      ensure continuing improvements. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00694018; http://clinicaltrials.gov/ct2/show/NCT00694018 (Archived by WebCite
      at http://www.webcitation.org/6IsG4Y90E).

PMID- 23969030
TI  - Sputum interleukin-6, tumor necrosis factor-alpha and Salivary cortisol as new
      biomarkers of depression in lung cancer patients.
AB  - Depression is common among lung cancer patients. Increasing evidence has
      suggested that hypothalamic-pituitary-adrenal (HPA) axis and pro-inflammatory
      cytokines may play a key role in the pathophysiology of depression as well as
      cancer. This pilot study investigated the efficacy of sputum interleukin (IL)-6,
      tumor necrosis factor (TNF)-alpha and salivary cortisol as new markers to support
      the diagnosis of depression in lung cancer patients. The diurnal rhythms of
      sputum IL-6, sputum TNF-alpha and salivary cortisol were measured in lung cancer
      patients with and without depression as well as depressed controls and healthy
      controls. The area under the diurnal variation curves (AUC) over the 24h time
      course and relative diurnal variation (VAR) were calculated. Receiver operating
      characteristic (ROC) analysis was performed. Patients with co-morbid depression
      and lung cancer showed highest level of sputum IL-6 AUC, sputum TNF-alpha AUC and
      lowest level of cortisol VAR (P<0.001). As a biomarker for depression, salivary
      cortisol VAR demonstrated an optimal cutoff point at 77.8% (AUC=0.94; 95% CI,
      0.85-0.98), which is associated with a sensitivity of 82.1% and a specificity of
      96.0%. Sputum IL-6 AUC demonstrated a sensitivity of 74.4% and a specificity of
      92.0% (AUC=0.81; 95% CI, 0.69-0.90). These findings suggested that higher 24h
      overall levels of sputum IL-6, TNF-alpha and flattened diurnal salivary cortisol
      slopes were associated with depression in lung cancer patients. Sputum IL-6 AUC
      and salivary cortisol VAR performed best as biomarkers in the diagnosis of
      depression in lung cancer patients. 

PMID- 23969031
TI  - Bacterial flora on Cascades frogs in the Klamath mountains of California.
AB  - Amphibians are experiencing global declines due in part to the infectious disease
      chytridiomycosis. Some symbiotic bacteria residents on frog skin have been shown
      to inhibit the growth of Batrachochytrium dendrobatitis (Bd) but few studies have
      attempted to fully describe the resident bacterial flora of frog skin. We
      cultured and sequenced 130 bacterial isolates from frogs collected from the
      California Klamath Range, recovering predominantly Gram-negative bacteria from 20
      higher order taxa and 31 genera. There were also a large number of unclassifiable
      isolates. Forty-three isolates were assessed for their ability to inhibit the
      growth of Bd in vitro; of these, two had strong and three had slight anti-Bd
      activity. We suggest that many bacterial species may play a secondary role in Bd
      resistance, acting synergistically with inhibitory species. Future research is
      required in order to characterize these interactions. Understanding the
      relationships between bacterial strains may be important in predicting and
      managing the effects of future anti-Bd treatments such as antimicrobial compounds
      or probiotic bacteria. 

PMID- 23969032
TI  - Utilization of elongation factor Tu gene (tuf) sequencing and species-specific
      PCR (SS-PCR) for the molecular identification of Acetobacter species complex.
AB  - The aim of this study was to use tuf gene as a molecular target for species
      discrimination in the Acetobacter genus, as well as to develop species-specific
      PCR method for direct species identification of Acetobacter aceti. The results
      showed that most Acetobacter species could be clearly distinguished, and the
      average sequence similarity for the tuf gene (89.5%) among type strains was
      significantly lower than that of the 16S rRNA gene sequence (98.0%). A pair of
      species-specific primers were designed and used to specifically identify A.
      aceti, but none of the other Acetobacter strains. Our data indicate that the
      phylogenetic relationships of most strains in the Acetobacter genus can be
      resolved using tuf gene sequencing, and the novel species-specific primer pair
      could be used to rapidly and accurately identify the species of A. aceti by the
      PCR based assay.

PMID- 23969033
TI  - Update on necrobiosis lipoidica: a review of etiology, diagnosis, and treatment
      options.
AB  - Necrobiosis lipoidica (NL) is a rare chronic granulomatous disease that has
      historically been associated with diabetes mellitus. Debate exists regarding the
      etiology and pathogenesis of NL with a widely accepted theory that
      microangiopathy plays a significant role. NL typically presents clinically as
      erythematous papules on the front of the lower extremities that can coalesce to
      form atrophic telangiectatic plaques. NL is usually a clinical diagnosis, but if
      the clinical suspicion is uncertain, skin biopsy specimen can help differentiate
      it from sarcoidosis, necrobiotic xanthogranuloma, and granuloma annulare. NL is a
      difficult disease to manage despite a large armamentarium of treatment options
      that include topical and intralesional corticosteroids, immunomodulators,
      biologics, platelet inhibitors, phototherapy, and surgery. Randomized control
      trials are lacking to evaluate the many treatment methods and establish a
      standard regimen of care. Disease complications such as ulceration are common,
      and lesions should also be monitored for transition to squamous cell carcinoma, a
      less common sequelae. 

PMID- 23969034
TI  - Comparative study of direct and indirect immunofluorescence and of bullous
      pemphigoid 180 and 230 enzyme-linked immunosorbent assays for diagnosis of
      bullous pemphigoid.
AB  - BACKGROUND: Direct immunofluorescence (DIF), indirect immunofluorescence (IIF),
      and enzyme-linked immunosorbent assay (ELISA) are used for the laboratory
      diagnosis of bullous pemphigoid (BP). OBJECTIVE: The diagnostic value of DIF and
      IIF on rabbit and monkey esophagus or human salt-split skin and commercial ELISAs
      was assessed. METHODS: This was a single-center retrospective study where 313
      patients with BP were compared with 488 control subjects. RESULTS: DIF was the
      most sensitive test (90.8%) whereas sensitivities for IIF on rabbit esophagus,
      IIF on monkey esophagus, IIF on salt-split skin, BP180 ELISA, and BP230 ELISA
      were 76.0%, 73.2%, 73.3%, 72.0%, and 59.0%, respectively. The sensitivity of the
      serologic tests was 88.8% altogether. The specificities for DIF, IIF on rabbit
      esophagus, IIF on monkey esophagus, IIF on salt-split skin, BP180 ELISA, and
      BP230 ELISA were 98%, 96.5%, 97.1%, 100%, 94.1%, and 99.2%, respectively.
      LIMITATIONS: The retrospective nature of study was a limitation. Correlation of
      diagnostic data with clinical manifestations or disease course was not possible.
      CONCLUSIONS: In suspected BP, both serologic tests and DIF have to be performed
      because of a sensitivity issue. Although the ELISAs had a relatively low
      sensitivity, the serologic tests altogether almost reached the level of
      sensitivity of DIF. The specificities of all assays were excellent.

PMID- 23969035
TI  - New estimates of incidence of encephalitis in England.
AB  - Encephalitis causes high rates of illness and death, yet its epidemiology remains
      poorly understood. To improve incidence estimates in England and inform priority
      setting and treatment and prevention strategies, we used hospitalization data to
      estimate incidence of infectious and noninfectious encephalitis during 2005-2009.
      Hospitalization data were linked to a dataset of extensively investigated cases
      of encephalitis from a prospective study, and capture-recapture models were
      applied. Incidence was estimated from unlinked hospitalization data as 4.32
      cases/100,000 population/year. Capture-recapture models gave a best estimate of
      encephalitis incidence of 5.23 cases/100,000/year, although the models' indicated
      incidence could be as high as 8.66 cases/100,000/year. This analysis indicates
      that the incidence of encephalitis in England is considerably higher than
      previously estimated. Therefore, encephalitis should be a greater priority for
      clinicians, researchers, and public health officials.

PMID- 23969036
TI  - Oligonucleotide probes containing pyrimidine analogs reveal diminished hydrogen
      bonding capacity of the DNA adduct O6-methyl-G in DNA duplexes.
AB  - Oligonucleotide hybridization probes containing nucleoside analogs offer a
      potential strategy for binding specific DNA sequences that bear pro-mutagenic
      O(6)-G alkylation adducts. To optimize O(6)-Me-G-targeting probes, an
      understanding of how base pairs with O(6)-Me-G are stabilized is needed. In this
      study, we compared the ability of O(6)-Me-G and G to hydrogen bond with three
      pyrimidine-like nucleobases (Z, 4-thio-U, and 3-deaza-C) bearing varied hydrogen
      bond donor and acceptor groups. We found that duplexes containing the pyrimidine
      analog nucleoside:G pairs were more thermodynamically stable than those
      containing pyrimidine analog nucleoside:O(6)-alkyl-G pairs. Thus, hydrogen
      bonding alone was not sufficient to impart selectivity to probes that target O(6)
      G alkylation adducts in DNA. 

PMID- 23969037
TI  - Enantioselective binding of chiral 1,14-dimethyl[5]helicene-spermine ligands with
      B- and Z-DNA.
AB  - Duplex DNA adopts a right-handed B-DNA conformation under physiological
      conditions. Z-DNA, meanwhile, has a left-handed helical structure and is in
      equilibrium with right-handed B-DNA. We recently reported that the bisnaphthyl
      maleimide-spermine conjugate (1) induced a B- to Z-DNA transition with high
      efficiency at low salt concentrations. It was also found that the bisnaphthyl
      ligand (1) spontaneously transformed into the corresponding [5]helicene
      derivative (2). Because [5]helicene 2 can potentially be chiral and because the
      chiral discrimination of B- and Z-DNA is also of interest, we became interested
      in whether enatiomerically pure [5]helicene-spermine conjugates might
      discriminate the chirality of B- or Z-DNA. In this study, we have demonstrated an
      efficient synthesis of chiral DNA-binding ligands by the conjugation of a
      [5]helicene unit with a spermine unit. These chiral helicene ligands exhibited
      recognition of B- and Z-DNA, with (P)-3 displaying preference for B-DNA and (M)-3
      for Z-DNA. The characteristic features of the helicene-spermine ligands developed
      in this study include two points: the cationic spermine portion produces
      electrostatic interactions along the phosphate backbone of the minor groove, and
      the helicene forms complexes in an end-stacking mode. Such binding modes,
      together with the thermodynamic parameters, account for the mode of chiral
      recognition of (P)- and (M)-3 for B- and Z-DNA. 

PMID- 23969038
TI  - Targeting interleukin-6 receptor inhibits preterm delivery induced by
      inflammation.
AB  - Intrauterine infection is still a common trigger of preterm delivery (PTD) and
      also a determinant risk factor for the subsequent development of
      neurodevelopmental abnormalities in neonates. In this study, we examined the
      expressional pattern of various inflammatory cytokines such as interleukin-1beta
      (IL-1beta), IL-6 and tumor necrosis factor-alpha (TNF-alpha) in placentae
      complicated with severe chorioamnionitis (CAM) and found that IL-6 is mainly
      expressed in macrophages in villous mesenchyme by immunohistochemical analysis
      with anti-CD-68 antibody. Using an experimental lipopolysaccharide (LPS)-induced
      PTD model, the therapeutic potential of targeting this cytokine was investigated.
      Anti-IL-6 receptor antibody (MR16-1) was delivered 6 h before LPS treatment. Mice
      in the MR16-1 group had a significantly lower rate of PTD (17%) than in the
      controls (53%, P = 0.026). As a result, MR16-1 treatment significantly prolonged
      the gestational period (control; 18.4 +/- 1.7d, MR16-1; 19.8 +/- 1.5d, P = 0.007)
      without any apparent adverse events on the mice and their pups. In primary human
      amniotic epithelial cells, pretreatment with a humanized anti-human IL-6 receptor
      antibody, tocilizumab, significantly inhibited the production of prostaglandin E2
      induced by IL-6. In conclusion, IL-6 was strongly expressed mainly in macrophages
      in villous mesenchyme in placentae complicated with CAM. Anti-IL-6R antibody
      significantly decreased the rate of PTD in LPS-induced inflammatory model in
      mice, and inhibited PGE2 production from human primary amniotic epithelial cells.
      Targeting IL-6 signaling could be a promising option for the prevention of PTD
      and needs to be further explored for future clinical application. 

PMID- 23969040
TI  - Bacterial adhesion to antibiotic-loaded guided tissue regeneration membranes - a
      scanning electron microscopy study.
AB  - BACKGROUND/PURPOSE: Bacterial contamination of sites undergoing guided tissue
      regeneration (GTR) therapy may reduce the efficiency of periodontal regeneration.
      This study compared bacterial adhesion onto various GTR membranes incorporated
      with antibiotics. METHODS: Three barrier membranes, including expanded
      polytetrafluoroethylene (ePTFE) membrane, collagen membrane, and glycolide fiber
      membrane, were loaded with tetracycline or amoxicillin. The adhesion of
      Streptococcus mutans and Aggregatibacter actinomycetemcomitans onto the GTR
      membranes with or without antibiotics was analyzed using the scanning electron
      microscopy (SEM) analysis. RESULTS: The SEM analysis showed no apparent
      alteration in the physical structure of the membranes loaded with antibiotics.
      Both S. mutans and A. actinomycetemcomitans attached best on the collagen
      membranes, followed by the ePTFE membranes, and then the glycolide fiber
      membranes without antibiotics. Moreover, higher numbers of bacteria were observed
      on the fibril areas than on the laminar areas of the ePTFE membranes. The amounts
      of attached bacteria on the GTR membranes increased after longer incubation.
      Incorporation of tetracycline or amoxicillin greatly reduced the adhesion of S.
      mutans and A. actinomycetemcomitans onto all of the GTR membranes examined.
      CONCLUSION: Incorporation of tetracycline or amoxicillin greatly reduced adhesion
      of S. mutans or A. actinomycetemcomitans on the ePTFE, glycolide fiber, or
      collagen membranes. This finding indicates that it is valuable and effective to
      use the antibiotic-loaded GTR membranes for periodontal regeneration therapy.

PMID- 23969039
TI  - Prognostic factors for Taiwanese patients with cutaneous melanoma undergoing
      sentinel lymph node biopsy.
AB  - BACKGROUND/PURPOSE: Sentinel lymph node biopsy (SLNB) is a standard procedure in
      the management of clinically node-negative melanoma. However, few studies have
      been performed on SLNB in Asia, which is an acral melanoma-prevalent area. This
      study evaluated the clinicopathologic prognostic factors of disease-free survival
      (DFS) and overall survival (OS) in Taiwanese patients with cutaneous melanoma who
      received wide excision and SLNB. The prognosis of patients with false-negative
      (FN) SLNB was also evaluated. METHODS: Malignant melanoma cases were reviewed for
      518 patients who were treated between January 2000 and December 2011. Of these
      patients, 127 patients with node-negative cutaneous melanoma who received
      successful SLNB were eligible for inclusion in the study. RESULTS: The SLNB
      positive rate was 34.6%. The median DFS was 51.5 months, and the median OS was
      90.9 months at the median follow-up of 36.6 months. Multivariate analysis
      revealed that patients whose melanoma had a Breslow thickness greater than 2 mm
      had a significantly shorter DFS than patients whose melanoma had a Breslow
      thickness of 2 mm or less [hazard ratio (HR), 3.421; p = 0.005]. Independent
      prognostic factors of OS were a Breslow thickness greater than 2 mm (HR, 4.435; p
      = 0.002); nonacral melanoma (HR, 3.048; p = 0.001); and an age older than 65
      years (HR, 2.819; p = 0.036). During the follow-up period, 13 of 83 SLN-negative
      patients developed a regional nodal recurrence. The SLNB failure rate was 15.7%
      and the FN rate was 22.8%. Compared to patients with a true-positive SLNB,
      patients with FN SLNB had a significantly shorter DFS (p = 0.001) but no
      significant difference in OS (p = 0.262). CONCLUSION: Except for the pathologic
      subtypes, prognostic factors in Taiwan are similar to those used in other
      melanoma-prevalent countries. Identifying and closely monitoring patients at risk
      of nodal recurrence after a negative SLNB is important.

PMID- 23969041
TI  - Ozone therapy in the management and prevention of caries.
AB  - The purpose of this article was to assess the effectiveness of ozone therapy in
      the management and prevention of caries, reviewing clinical and in vitro studies.
      Ozone has proven to be effective against gram-negative and gram-positive
      bacteria, viruses, and fungi. In dentistry, most of the published articles are
      based on ozone's antimicrobial effects and the treatment of caries. Most of the
      clinical studies reported ozone to be a promising alternative to conventional
      methods for caries management. However, a few studies have shown ozone to be
      insufficient for preventing caries and reducing microorganisms in open occlusal
      carious lesions. Ozone might be a useful tool to reduce and control oral
      infectious microorganisms in dental plaque and dental cavity. However, the
      results of in vitro studies are controversial; while some researchers reported
      that ozone therapy had a minimal or no effect on the viability of microorganisms,
      others suggested ozone to be highly effective in killing both gram-positive and
      gram-negative oral microorganisms. Therefore, more evidence is required before
      ozone can be accepted as an alternative to present methods for the management and
      prevention of caries.

PMID- 23969042
TI  - Langerhans cells in the lining epithelia of odontogenic cysts.

PMID- 23969043
TI  - Frequency power and coherence of electroencephalography are correlated with the
      severity of Alzheimer's disease: A multicenter analysis in Taiwan.
AB  - BACKGROUND/PURPOSE: Slowing of average electroencephalography (EEG) frequency in
      Alzheimer's disease (AD) is well established, but whether EEG changes are able to
      reflect the severity of AD is uncertain. We attempt to establish quantitative EEG
      parameters that are suitable for evaluating AD in clinical practice. METHODS:
      Ninety-five patients with newly diagnosed AD at different stages from four
      neurologic institutes were enrolled for the study. Standard scalp resting EEG
      data were collected for quantitative analysis. Global band power ratio and
      interhemispheric alpha band coherence were calculated. RESULTS: Patients with
      advanced AD had a greater slow-to-fast wave power ratio. Among several power
      ratio parameters, global theta and delta to alpha and beta band power ratio
      showed the best correlation with stages of AD (p < 0.05 between any two patient
      groups). Patients with advanced AD had decreased coherence in multiple brain
      regions. The phenomenon was most prominent in the centroparietal region (p < 0.05
      between any two patient groups). CONCLUSION: Increased global slow-to-fast power
      ratio and decreased centroparietal interhemispheric alpha band coherence are
      strongly correlated with disease progress in AD patients. These two quantitative
      EEG parameters may help evaluate AD patients in daily clinical practice. Global
      power ratio changes may suggest a shift of dominant frequency, and decreased
      interhemispheric alpha band coherence may suggest functional disconnection and
      corpus callosum abnormalities in AD patients.

PMID- 23969044
TI  - First case of neurognathostomiasis in Taiwan--A Thai laborer presenting with
      eosinophilic meningitis and intracranial hemorrhage.
AB  - We report a case of neurognathostomiasis in a Thai laborer for the first time in
      Taiwan. For patients with eosinophilic meningitis, neurognathostomiasis should be
      considered when brain image discloses subarachnoid or intracranial hemorrhage and
      when an appropriate exposure risk is available, especially a history of raw
      freshwater fish consumption in endemic areas, even a long time ago. 

PMID- 23969045
TI  - Complete Genome Sequence of Cyanobacterial Siphovirus KBS2A.
AB  - We present the genome of a cyanosiphovirus (KBS2A) that infects a marine
      Synechococcus sp. (strain WH7803). Unique to this genome, relative to other
      sequenced cyanosiphoviruses, is the absence of elements associated with
      integration into the host chromosome, suggesting this virus may not be able to
      establish a lysogenic relationship. 

PMID- 23969046
TI  - Genome Sequence of Salmonella bongori Strain N268-08 [corrected].
AB  - Salmonella bongori is a close relative of the highly virulent members of S.
      enterica subspecies enterica, encompassing more than 2,500 serovars, most of
      which cause human salmonellosis, one of the leading food-borne illnesses. S.
      bongori is only very rarely implicated in infections. We here present the
      sequence of a clinical isolate from Switzerland, S. bongori strain N268-08. 

PMID- 23969047
TI  - Complete Genome Sequence for Lactobacillus helveticus CNRZ 32, an Industrial
      Cheese Starter and Cheese Flavor Adjunct.
AB  - Lactobacillus helveticus is a lactic acid bacterium widely used in the
      manufacture of cheese and for production of bioactive peptides from milk
      proteins. We present the complete genome sequence for L. helveticus CNRZ 32, a
      strain particularly recognized for its ability to reduce bitterness and
      accelerate flavor development in cheese. 

PMID- 23969048
TI  - Genome Sequence of the Food Spoilage Yeast Zygosaccharomyces bailii CLIB 213T.
AB  - The ascomycetous yeast Zygosaccharomyces bailii is one of the most problematic
      spoilage yeasts in food and beverage industries, due to its exceptional
      resistance to various stresses. A better understanding of the molecular
      mechanisms underlying these stress resistance phenotypes might help develop
      strategies to improve food quality. Thus, we determined and annotated the genome
      sequence of the strain Z. bailii CLIB 213(T) (= CBS 680). 

PMID- 23969049
TI  - Complete genome sequence analysis of a reassortant strain of bluetongue virus
      serotype 16 from Italy.
AB  - The complete genome sequence of a reassortant field strain of bluetongue virus
      serotype 16 (BTV-16), isolated from cattle in the Apulia region of Italy in 2002,
      has been determined by Illumina sequencing. Sequence comparisons of segment 1
      (Seg-1) to Seg-10, except Seg-5, show that BTV-16 strain ITL2002 belongs to the
      major eastern topotype of BTV. 

PMID- 23969050
TI  - Full Genome Sequence of Egg Drop Syndrome Virus Strain FJ12025 Isolated from
      Muscovy Duckling.
AB  - Egg drop syndrome virus (EDSV) strain FJ12025 was isolated from a 9-day-old
      Muscovy duckling. The results of the sequence showed that the genome of strain
      FJ12025 is 33,213 bp in length, with a G+C content of 43.03%. When comparing the
      genome sequence of strain FJ12025 to that of laying duck original strain AV-127,
      we found 50 single-nucleotide polymorphisms (SNPs) between the two viral genome
      sequences. A genomic sequence comparison of FJ12025 and AV-127 will help to
      understand the phenotypic differences between the two viruses. 

PMID- 23969051
TI  - Draft Genome Sequence of Lactobacillus gasseri Strain 2016.
AB  - Different common factors contribute to the antagonistic properties of
      Lactobacillus gasseri toward various pathogens. However, there is strain-to
      strain variation in the probiotic properties of this bacterium. The draft genome
      sequence of L. gasseri strain 2016 determined in this study will assist in
      understanding the genetic basis for such variation. 

PMID- 23969052
TI  - Complete Genome Sequence of a Very Virulent Porcine Epidemic Diarrhea Virus
      Strain, CH/GDGZ/2012, Isolated in Southern China.
AB  - The classical symptoms of porcine epidemic diarrhea (PED) are acute diarrhea and
      dehydration. The isolated porcine epidemic diarrhea virus (PEDV) CH/GDGZ/2012
      strain was obtained from the feces of diseased pigs in 2012 in southern China. We
      report the complete genome sequence of strain CH/GDGZ/2012, which might be useful
      for better understanding the molecular characteristics of this virus. 

PMID- 23969053
TI  - Draft Genome Sequence of the Fast-Growing Bacterium Vibrio natriegens Strain DSMZ
      759.
AB  - Vibrio natriegens is a Gram-negative bacterium known for its extremely short
      doubling time. Here we present the annotated draft genome sequence of Vibrio
      natriegens strain DSMZ 759, with the aim of providing insights about its high
      growth rate. 

PMID- 23969054
TI  - Genome Sequence of Salmonella enterica Serovar Typhi Oral Vaccine Strain Ty21a.
AB  - Attenuated Salmonella enterica serovar Typhi strain Ty21a is an important vaccine
      for controlling typhoid fever and serves as an oral vector for delivering
      heterologous antigens. The key attenuating features of this randomly mutated
      strain remain in question. Genome sequencing has revealed 679 single nucleotide
      polymorphisms (SNPs), and will help define alterations contributing to Ty21a
      safety and immunogenicity. 

PMID- 23969055
TI  - Genome Sequence of the Quorum-Quenching Agrobacterium tumefaciens Strain WRT31.
AB  - Agrobacterium tumefaciens strain WRT31 is a quorum-sensing signal-degrading
      bacterium that has been isolated from the rhizosphere of tobacco plants. This
      strain belongs to A. tumefaciens genomovar G1, is avirulent on various putative
      host plants, devoid of Ti plasmid, and contains the blcC gene encoding a gamma
      butyrolactonase. 

PMID- 23969056
TI  - Complete Genomic Sequences of an H3N8 Equine Influenza Virus Strain Isolated in
      China.
AB  - We report the complete genomic sequence of A/equine/Heilongjiang/1/2010, a strain
      of Florida sublineage clade 2 of H3N8 subtype equine influenza virus (EIV)
      isolated in northern China. This is the first announcement of a complete genomic
      sequence of EIV of such a clade in China. 

PMID- 23969057
TI  - Complete Genome Sequence of the Arcobacter butzleri Cattle Isolate 7h1h.
AB  - Arcobacter butzleri strain 7h1h was isolated in the United Kingdom from the feces
      of a clinically healthy dairy cow. The genome of this isolate was sequenced to
      completion. Here, we present the annotation and analysis of the completed 7h1h
      genome, along with a comparison of this genome to the existing A. butzleri
      genomes. 

PMID- 23969058
TI  - Complete Genome Sequence of the Encephalomyelitic Burkholderia pseudomallei
      Strain MSHR305.
AB  - We describe the complete genome sequence of Burkholderia pseudomallei MSHR305, a
      clinical isolate taken from a fatal encephalomyelitis case, a rare form of
      melioidosis. This sequence will be used for comparisons to identify the genes
      that are involved in neurological cases. 

PMID- 23969059
TI  - Draft Genome Sequences of Five Strains of Lactobacillus acidophilus, Strain CIP
      76.13T, Isolated from Humans, Strains CIRM-BIA 442 and CIRM-BIA 445, Isolated
      from Dairy Products, and Strains DSM 20242 and DSM 9126 of Unknown Origin.
AB  - Lactobacillus acidophilus is a natural inhabitant of mammalian gastrointestinal
      systems and is used in dairy and pharmaceutical products. Five draft genome
      sequences, covering 1,995,790 nucleotides (nt) on average, are divided into 19 to
      34 scaffolds covering 1,995 to 2,053 genes. The draft genome sequences were
      compared to the sequence of the L. acidophilus NCFM dairy strain. 

PMID- 23969060
TI  - Draft Genome Sequences of Vibrio cholerae O1 ElTor Strains 2011EL-301 and P
      18785, Isolated in Russia.
AB  - We report the draft whole-genome sequences of two Vibrio cholerae O1 strains, the
      environmental toxigenic strain 2011EL-301 and the clinical nontoxigenic strain P
      18785, both isolated in Russia. Some basic data comparing the two against the
      GenBank repository are provided. 

PMID- 23969061
TI  - Draft Genome Sequence of Lactobacillus pasteurii CRBIP 24.76T.
AB  - We report the draft genome sequence of the type strain Lactobacillus pasteurii
      CRBIP 24.76, which is closely related to L. gigeriorum CRBIP 24.85(T), isolated
      from a chicken crop. The total length of the 29 contigs is about 1.9 Mb, with a
      G+C content of 40% and 1,946 coding sequences. 

PMID- 23969062
TI  - Draft Genome Sequence of Lactobacillus hominis Strain CRBIP 24.179T, Isolated
      from Human Intestine.
AB  - We report the draft genome sequence of the strain Lactobacillus hominis CRBIP
      24.179(T), isolated from a human clinical sample. The total length of the 28
      contigs is about 1.9 Mb, with a G+C content of 37% and 1,983 coding sequences. 

PMID- 23969063
TI  - Draft Genome Sequences of Lactobacillus equicursoris CIP 110162T and
      Lactobacillus sp. Strain CRBIP 24.137, Isolated from Thoroughbred Racehorse Feces
      and Human Urine, Respectively.
AB  - We report the draft genome sequences of strain Lactobacillus equicursoris CIP
      110162(T), isolated from racehorse breed feces, and Lactobacillus sp. strain
      CRBIP 24.137, isolated from human urine; the two strains are closely related. The
      total lengths of the 116 and 62 scaffolds are about 2.157 and 2.358 Mb, with G+C
      contents of 46 and 45% and 2,279 and 2,342 coding sequences (CDSs), respectively.

PMID- 23969064
TI  - Draft Genome Sequence of Holospora undulata Strain HU1, a Micronucleus-Specific
      Symbiont of the Ciliate Paramecium caudatum.
AB  - Holospora undulata is a micronucleus-specific symbiont of the ciliate Paramecium
      caudatum. We report here the draft genome sequence of H. undulata strain HU1.
      This genome information will contribute to the study of symbiosis between H.
      undulata and the host P. caudatum. 

PMID- 23969065
TI  - Numerical simulation of Electron Energy Loss Spectroscopy using a Generalized
      Multipole Technique.
AB  - We numerically simulate low-loss Electron Energy Loss Spectroscopy (EELS) of
      isolated spheroidal nanoparticles, using an electromagnetic model based on a
      Generalized Multipole Technique (GMT). The GMT is fast and accurate, and, in
      principle, flexible regarding nanoparticle shape and the incident electron beam.
      The implemented method is validated against reference analytical and numerical
      methods for plane-wave scattering by spherical and spheroidal nanoparticles.
      Also, simulated electron energy loss (EEL) spectra of spherical and spheroidal
      nanoparticles are compared to available analytical and numerical solutions. An
      EEL spectrum is predicted numerically for a prolate spheroidal aluminum
      nanoparticle. The presented method is the basis for a powerful tool for the
      computation, analysis and interpretation of EEL spectra of general geometric
      configurations. 

PMID- 23969066
TI  - Probe integrated scattering cross sections in the analysis of atomic resolution
      HAADF STEM images.
AB  - The physical basis for using a probe-position integrated cross section (PICS) for
      a single column of atoms as an effective way to compare simulation and experiment
      in high-angle annular dark-field (HAADF) scanning transmission electron
      microscopy (STEM) is described, and the use of PICS in order to make quantitative
      use of image intensities is evaluated. It is based upon the calibration of the
      detector and the measurement of scattered intensities. Due to the predominantly
      incoherent nature of HAADF STEM, it is found to be robust to parameters that
      affect probe size and shape such as defocus and source coherence. The main
      imaging parameter dependencies are on detector angle and accelerating voltage,
      which are well known. The robustness to variation in other parameters allows for
      a quantitative comparison of experimental data and simulation without the need to
      fit parameters. By demonstrating the application of the PICS to the chemical
      identification of single atoms in a heterogeneous catalyst and in thin, layered
      materials, we explore some of the experimental considerations when using this
      approach. 

PMID- 23969068
TI  - New terminology for headache/migraine as the sole ictal epileptic manifestation:
      the downsides. Reply to Cianchetti et al.

PMID- 23969067
TI  - 7,12-Dimethylbenz[a]anthracene exposure induces the DNA repair response in
      neonatal rat ovaries.
AB  - 7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all stages of
      development. This study investigated DMBA-induced DNA double strand break (DSB)
      formation with subsequent activation of the ovarian DNA repair response in models
      of pre-antral or pre-ovulatory follicle loss. Postnatal day (PND) 4 Fisher 344
      (F344) rat ovaries were cultured for 4 days followed by single exposures of
      vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and maintained in culture
      for 4 or 8 days. Alternately, PND4 F344 rat ovaries were exposed to 1 MUM DMBA at
      the start of culture for 2 days. Total RNA or protein was isolated, followed by
      qPCR or Western blotting to quantify mRNA or protein level, respectively.
      gammaH2AX and phosphorylated ATM were localized and quantified using
      immunofluorescence staining. DMBA exposure increased caspase 3 and gammaH2AX
      protein. Additionally, DMBA (12.5 nM and 1 MUM) increased levels of mRNA encoding
      Atm, Xrcc6, Brca1 and Rad51. In contrast, Parp1 mRNA was decreased on d4 and
      increased on d8 of DMBA exposure, while PARP1 protein increased after 8 days of
      DMBA exposure. Total ATM increased in a concentration-dependent temporal pattern
      (75 nM d4; 12.5 nM d8), while pATM was localized in large primary and secondary
      follicles and increased after 8 days of 75 nM DMBA exposure compared to both
      control and 12.5 nM DMBA. These findings support that, despite some concentration
      effects, DMBA induces ovarian DNA damage and that DNA repair mechanisms are
      induced as a potential mechanism to prevent follicle loss.

PMID- 23969069
TI  - Prevalence and clinical, electrocardiographic, and electrophysiologic
      characteristics of ventricular arrhythmias originating from the noncoronary sinus
      of Valsalva.
AB  - BACKGROUND: Idiopathic ventricular arrhythmias (VAs) can be rarely ablated from
      the noncoronary cusp (NCC) of the aorta. OBJECTIVE: The purpose of this study was
      to investigate the prevalence and the clinical, electrocardiographic, and
      electrophysiologic characteristics of idiopathic NCC VAs. METHODS: We studied 90
      consecutive patients who underwent successful catheter ablation of idiopathic
      aortic root VAs (left coronary cusp [LCC] 33, right coronary cusp [RCC] 32,
      junction between LCC and RCC 19, NCC = 6). RESULTS: NCC VAs occurred in
      significantly younger patients (all <40 years old) and exhibited a shorter QRS
      duration (all but one <150 ms), smaller R-wave amplitude ratio in leads II and
      III (III/II), earlier ventricular activation in the His bundle (HB) region (all
      but one preceded QRS onset by >25 ms), and larger atrial to ventricular
      electrogram amplitude ratio (A/V) at the successful ablation site (all but one
      >1) than the other VAs. QRS morphology of the NCC VAs was similar to that of RCC
      VAs, but NCC VAs always exhibited a left bundle branch block and left superior (n
      = 1) or inferior axis (n = 5). All NCC VAs exhibited ventricular tachycardias,
      although premature ventricular contractions were dominant in the other VAs.
      CONCLUSION: NCC VAs were very rare (7%) and occurred in significantly younger
      patients than those among the other aortic root VAs. In a limited set of six
      patients, the ECG and electrophysiologic characteristics of NCC VAs were similar
      to those of RCC VAs but were characterized by narrower QRS duration, smaller
      III/II ratio, earlier ventricular activation in the HB region, and A/V ratio >1
      at the successful ablation site.

PMID- 23969070
TI  - The Canadian Durata experience: grounds for cautious optimism?

PMID- 23969071
TI  - Rotors: Linking VF and VT?

PMID- 23969072
TI  - Risk factors affecting asthma prevalence in adolescents living in Istanbul,
      Turkey.
AB  - BACKGROUND: Asthma is one of the most important diseases of childhood. The aim of
      this study was to evaluate the prevalence of asthma symptoms and risk factors
      affecting asthma. METHODS: In a cross-sectional study design, 9991 children, aged
      13-14 years in 61 primary schools in 32 districts of Istanbul were evaluated.
      Asthma prevalence among the children was assessed using the ISAAC protocol.
      RESULTS: In our study, a total of 10,894 questionnaires were distributed to 13-14
      years old children, and of these 9991 questionnaires were suitable for analysis
      with an overall response rate of 91.7%. The rates of wheeze ever, wheezing in
      last 12 months and lifetime doctor diagnosed asthma prevalence were 17.4%, 9.0%,
      and 11.8%, respectively. There were 4746 boys (47.9%) and 5166 girls (52.1%) with
      M/F ratio of 0.92. Atopic family history, fewer than three siblings living at
      home, tonsillectomy or adenoidectomy history, consumption of fermented foods,
      mixed pickles, margarine and meat were found to be associated with an increased
      asthma risk. Use of paracetamol in the last 12 months, consumption of fruit and
      animal fats acted as a protective factor against asthma. The Mediterranean-style
      diet was not associated with the prevalence of asthma. CONCLUSIONS: Lifetime
      doctor diagnosed asthma prevalence was found to be 11.8% in 13-14 year olds.
      History of tonsillectomy and/or adenoidectomy and consumption of fermented foods,
      mixed pickles, margarine and meat may increase the symptoms of asthma. Usage of
      paracetamol and consumption of animal fats may be investigated as a protective
      factor against asthma.

PMID- 23969073
TI  - The role of mean platelet volume as an inflammatory marker in children with
      chronic spontaneous urticaria.
AB  - BACKGROUND: Previous studies have shown that platelets are involved in the
      inflammatory process. Mean platelet volume (MPV) has been frequently used as an
      inflammatory marker in various diseases associated with inflammation. The role of
      MPV in children with chronic spontaneous urticaria (CU), however, has not yet
      been evaluated. In this study we compared MPV levels between children with and
      without CU. METHODS: Children with CU and age-matched healthy children were
      enrolled in the study. Complete blood count and C-reactive protein (CRP) levels
      were assessed in children with CU whilst MPV levels were compared between
      children with and without CU. RESULTS: Forty children with CU (19 males; mean
      age: 8.0 +/- 3.8 year; range: 3-15 years) and 40 healthy children (17 males; mean
      age: 6.9 +/- 3.0 year; range: 2-14 year) were enrolled on the prospective, case
      control study. MPV (fL) levels were significantly lower in children with CU when
      compared to healthy children (7.42 +/- 0.77 and 7.89 +/- 0.65, respectively;
      p=0.004). Both mean platelet number and median CRP levels were significantly
      higher in children with CU when compared to healthy children (p=0.008, p=0.014,
      respectively). CONCLUSION: To our knowledge, this study is the first to evaluate
      the role of MPV as an inflammatory marker in children with CU. A decline in MPV
      may be considered as an indicator of inflammation in children with CU.

PMID- 23969074
TI  - Prevalence of asthma, local risk factors and agreement between written and video
      questionnaires among Turkish adolescents.
AB  - BACKGROUND: There is currently no standard tool for the measurement of asthma in
      epidemiological studies. The objectives of this study were to determine the
      prevalence of asthma, to describe the potential local risk factors, and to assess
      the agreement between written and video questionnaires in 13- to 14-year-old
      schoolchildren. METHODS: We performed a cross-sectional study involving 5427
      adolescents in 26 schools. Prevalence of asthma symptoms were evaluated using the
      International Study of Asthma and Allergies in Childhood (ISAAC) written and
      video questionnaire. The adolescents were asked additional questions for risk
      factors of asthma. RESULTS: The prevalence of lifetime wheeze, wheeze in the last
      12 months and doctor-diagnosed asthma with written questionnaire were found as
      13.5%, 6.3% and 11.2% respectively. Prevalence of lifetime wheeze, wheeze in the
      last 12 months, wheeze after exercise in the last 12 months, with video
      questionnaire were found as 9.6%, 5.5%, 11.9% and 1.9% respectively. The
      proportion of total agreement between the two questionnaires was high (0.77-0.81)
      with poor kappa value (0.25-0.50). In multivariate analysis, family history of
      atopy, stuffed toys and accompaniment of children to their parents after school
      hours in textile industry were found as risk factors for asthma. In addition kind
      of bird, such as canary was found as a risk factor. CONCLUSION: Prevalence of
      asthma is moderate in Turkey. Agreement between the two questionnaires was high.
      Accompaniment of children to their parents in textile industry is a newly
      described risk factor for asthma.

PMID- 23969075
TI  - Increased level of interleukin-13, but not interleukin-4 and interferon-gamma in
      chronic rhinosinusitis with nasal polyps.
AB  - BACKGROUND: This study was performed to investigate the serum level of
      interleukin (IL)-13, IL-4, and interferon (IFN)-gamma in chronic rhinosinusitis
      with nasal polyps (CRSwNP) and subsequent inflammation pattern and comorbidities
      including asthma and aspirin intolerance. METHODS: A case-control study was
      conducted on 60 adult patients with CRSwNP with mean age of 37.7+/-12.7 (ranging
      from 18 to 70) years, and on 20 healthy controls. Serum levels of IL-13, IL-4,
      and IFN-gamma were assessed, using enzyme-linked immunosorbent assay to be
      compared between case and control groups. Serum level of total immunoglobulin
      (Ig) E was also assessed in the patients with CRSwNP. RESULTS: Serum level of IL
      13 in the patients with CRSwNP was significantly higher than the controls (0.98+/
      1.56 vs. 0.34+/-0.16 pg/ml, respectively, p=0.002). IL-4 and IFN-gamma did not
      differ significantly between the two groups. Total IgE level was significantly
      increased in the patients with CRSwNP, compared to the normal values (301.43+/
      516.54 IU/ml, p=0.033). Among the patients with CRSwNP, 12/60 (20%) had aspirin
      intolerance and 44/60 (73.3%) had asthma. IgE was also higher in asthmatics than
      non-asthmatics patients (364.9+/-586.6 vs. 126.7+/-135.7, respectively, p=0.015).
      Patients with aspirin intolerance had higher levels of IFN-gamma (4.7+/-1.4 vs.
      4.1+/-0.6, respectively, p=0.022). CONCLUSIONS: IL-13 with high level of total
      IgE was observed in the patients with CRSwNP, which predisposes them to have
      concomitant asthma. IFN-gamma seems to be down-regulated in the patients with
      CRSwNP, but could be over-expressed in the presence of aspirin intolerance.

PMID- 23969076
TI  - [PAIR for complex hepatic hydatid disease].

PMID- 23969077
TI  - Exploration of the six tryptophan residues of Escherichia coli cystathionine beta
      lyase as probes of enzyme conformational change.
AB  - Cystathionine beta-lyase (CBL) catalyzes the hydrolysis of l-cystathionine (l
      Cth), producing l-homocysteine (l-Hcys), pyruvate and ammonia, in the second step
      of the transsulfuration pathway of bacteria and plants. A series of 17 site
      directed variants of Escherichia coli CBL (eCBL) was constructed to probe the
      contributions of the six tryptophan residues (W131, W188, W230, W276, W300 and
      W340) to the fluorescence spectrum of eCBL and to assess their mutability and
      utility as conformational probes. The effects of these Trp->Phe substitutions on
      kcat and Km(l)(-Cth) are less than 2-fold, with the exception of the 8-fold
      increase in Km(l)(-Cth) observed for eCBL-W340F. The midpoint of thermal
      denaturation, as monitored by circular dichroism spectroscopy, is reduced 4.7
      degrees C by the W188F substitution while the targeted replacement of the other
      five tryptophans alter Tm by less than 1.7 degrees C. The fluorescence spectrum
      of eCBL is dominated by W230 and the contribution of W340, situated in the active
      site, is minor. The observed 5-fold increase in the 336 nm fluorescence emission
      of W188 between 0 and 2M urea, suggests a conformational change at the domain
      interface. Residues W188 and W340, conserved in proteobacterial CBL enzymes, are
      situated at the core of the domain interface that forms the active-site cleft.
      The results of this study suggest that W188 is a useful probe of subtle
      conformational changes at the domain interface and active site.

PMID- 23969079
TI  - The treatment of hypertension in care home residents: a systematic review of
      observational studies.
AB  - AIM: To describe the prevalence of hypertension in care home residents, its
      treatment, change in treatment over time, and the achievement of blood pressure
      (BP) control. METHOD: The PubMed, Cochrane, Embase, and PsychINFO databases were
      searched for observational studies involving care home residents with a diagnosis
      of hypertension. The search was limited to English language articles involving
      adults and humans published from 1990 onward. Abstracts and titles were reviewed
      with eligible articles read in full. Bibliographies were examined for further
      relevant studies. The final selection of studies was then analyzed and appraised.
      RESULTS: Sixteen articles were identified for analysis, of which half were
      studies carried out in the United States. The prevalence of hypertension in care
      home residents was 35% (range 16%-71%); 72% of these were on at least 1
      antihypertensive (mean 1.5 antihypertensives per individual), with diuretics
      being the most common. The prevalence of hypertension in study populations was
      greater in more recent studies (P = .004). ACEi/ARBs (P = .001) and beta-blockers
      (P = .04) were prescribed more frequently in recent studies, whereas use of
      calcium-channel blockers and diuretics remained unchanged over time. The number
      of antihypertensives prescribed per patient was higher (correlation 0.332, P =
      .009), whereas fewer patients achieved target BP (correlation -0.671, P = .099)
      in more recent studies. CONCLUSION: Hypertension is common in care home residents
      and is commonly treated with antihypertensive drugs, which were prescribed more
      frequently in more recent studies but with no better BP control. These studies
      indicate a tendency toward increasing polypharmacy over time, with associated
      risk of adverse events, without demonstrable benefit in terms of BP control.

PMID- 23969078
TI  - Similar molecules spatially correlate with lipofuscin and N-retinylidene-N
      retinylethanolamine in the mouse but not in the human retinal pigment epithelium.
AB  - The accumulation of lipofuscin in the retinal pigment epithelium (RPE) has been
      implicated in the development of age-related macular degeneration (AMD) in
      humans. The exact composition of lipofuscin is not known but its best
      characterized component is N-retinylidene-N-retinylethanolamine (A2E), a
      byproduct of the retinoid visual cycle. Utilizing our recently developed matrix
      assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS)-based
      technique to determine the spatial distribution of A2E, this study compares the
      relationships of lipofuscin fluorescence and A2E in the murine and human RPE on
      representative normal tissue. To identify molecules with similar spatial
      patterns, the images of A2E and lipofuscin were correlated with all the
      individual images in the MALDI-IMS dataset. In the murine RPE, there was a
      remarkable correlation between A2E and lipofuscin. In the human RPE, however,
      minimal correlation was detected. These results were reflected in the marked
      distinctions between the molecules that spatially correlated with the images of
      lipofuscin and A2E in the human RPE. While the distribution of murine lipofuscin
      showed highest similarities with some of the known A2E-adducts, the composition
      of human lipofuscin was significantly different. These results indicate that A2E
      metabolism may be altered in the human compared to the murine RPE.

PMID- 23969080
TI  - Inflammatory pathways in spondyloarthritis.
AB  - Spondyloarthritis is the second most common form of chronic inflammatory
      arthritis and a unique hallmark of the disease is pathologic new bone formation.
      Several cytokine pathways have been genetically associated with ankylosing
      spondylitis (AS), the prototypic subtype of SpA, and additional evidence from
      human and animal studies support a role of these pathways in the disease. TNF has
      a key role in SpA as blockade significantly reduces inflammation and destruction,
      however the treatment does not halt new bone formation. New insights into the TNF
      pathway were recently obtained from an animal model specifically overexpressing
      the transmembrane form of TNF. This model leads to axial and peripheral new bone
      formation which is not seen in soluble TNF overexpression models, indicating
      different pathogenic roles of soluble and transmembrane TNF in arthritis
      development. Besides TNF, the IL-23/IL-17 axis is emerging as an important
      inflammatory pathway in SpA, as a SNP in the IL-23R locus has been associated
      with developing AS, mice overexpressing IL-23 develop SpA-like features and IL-17
      blockade has been shown to be efficacious for AS patients in a phase II trial. In
      this review, we focus on the cytokine pathways that have recently been
      genetically associated with SpA, i.e. TNF, IL-1, IL-6 and IL-23/IL-17. We review
      the current genetic, experimental and human in vivo data available and discuss
      how these different pathways are involved in the pathophysiology of SpA.
      Additionally, we discuss how these pathways relate to the pathogenic new bone
      formation in SpA. 

PMID- 23969081
TI  - Does circadian rhythm disruption induced by light-at-night has beneficial effect
      of melatonin on sciatic nerve injury?
AB  - Melatonin stimulates peripheral nerve regeneration. However, the precise effect
      of Melatonin on nerve repair in dark period have not been clarified. The aim of
      the present study was to investigate the effect of melatonin on sciatic nerve
      injury after melatonin was given to rats in the morning or evening by means of
      combined analysis. This is the first study to investigate the influence of
      melatonin on sciatic nerve in cut injury two different times of the day. 60 adult
      female Wistar rats were divided into 4 groups: control (Group 1), sham-operated
      (Group 2), sciatic nerve cut+melatonin treatment in light (Group 3), sciatic
      nerve cut+melatonin treatment in dark (Group 4). Melatonin was administered
      intraperitoneally at dose of 50 mg/kg/day for six weeks. Recovery of function was
      analyzed by structural (biochemical properties of the antioxidant levels and
      ultrastructural analysis) and functional analyses (Sciatic function index, pinch
      test). The data demonstrated beneficial effect of melatonin in light period.
      However significant beneficial effect of melatonin was detected on the recovery
      of the cut sciatic nerve in dark period. Melatonin treatment was unable to
      influence on the recovery of the cut sciatic nerve in dark period. This means
      that the effect of melatonin the recovery of the cut injured sciatic nerve
      depends on the time of treatment may be attributed to its circadian rhythm.

PMID- 23969082
TI  - A case of pseudogout of the temporomandibular joint with giant cell reparative
      granuloma of the temporal bone.
AB  - Pseudogout, also known as calcium pyrophosphate dihydrate deposition disease
      (CPPD) with giant cell reparative granuloma (GCRG) of the temporal bone is a rare
      disease, which is very easy to misdiagnose. When two diseases occur
      simultaneously, the pathological tissue of diseases is closely associated, which
      complicates clinical representation and causes enormous difficulty in diagnosis
      and treatment. We report a case of CPPD of the temporomandibular joint
      accompanied by surrounding GCRG of temporal bone in a 62-year-old male. 

PMID- 23969083
TI  - A BALB/c mouse model for assessing the potential allergenicity of proteins:
      comparison of allergen dose, sensitization frequency, timepoint and sex.
AB  - The present study was to investigate the possibility of using the BALB/c mouse as
      an animal model for assessing the potential allergenicity of proteins. Specific
      IgE and IgG1 against ovalbumin were induced by dosing BALB/c mice via
      intraperitoneal injection (absence of adjuvant). The effects of various allergen
      doses (5 mg, 0.5 mg or 0.05 mg OVA), sensitization times (twice or five times),
      timepoints (day 14 or day 28) and sex (male or female) were studied. IL-4, IFN
      gamma, OVA-specific IgE and IgG1 were measured by enzyme-linked immunosorbent
      assay (ELISA). A general finding was that mice treated with 0.05 mg OVA had the
      highest OVA-specific IgE and IgG1, statistically significant higher specific IgE
      and IgG1 were observed in groups sensitized five times than twice, OVA-specific
      IgE and IgG1 on day 28 were statistically higher than day 14, and higher IL-4 was
      observed in OVA-allergic mice than control mice. These results demonstrate that
      the BALB/c mouse model treated with 0.05 mg OVA intraperitoneally on days 0, 3,
      6, 9, 12 might be used for further experiments. OVA-specific IgE and IgG1 should
      be detected on day 28. Further studies including reproducibility and other
      conditions were required before using the BALB/c mouse model for assessing the
      potential allergenicity of proteins.

PMID- 23969084
TI  - Monitoring tumor response with [18F]FMAU in a sarcoma-bearing mouse model after
      liposomal vinorelbine treatment.
AB  - OBJECTIVE: Previous studies have shown that the accumulation level of FMAU in
      tumor is proportional to its proliferation rate. This study demonstrated that 2'
      deoxy-2'-[(18)F]fluoro-beta-d-arabinofuranosyluracil ([(18)F]FMAU) is a promising
      PET probe for noninvasively monitoring the therapeutic efficacy of 6% PEGylated
      liposomal vinorelbine (lipo-VNB) in a subcutaneous murine NG4TL4 sarcoma mouse
      model. METHODS: Female syngenic FVB/N mice were inoculated with NG4TL4 cells in
      the right flank. After tumor size reached 150 +/- 50 mm(3) (day 0), lipo-VNB
      (5mg/kg) was intravenously administered on days 0, 3 and 6. To monitor the
      therapeutic efficacy of lipo-VNB, [(18)F]FMAU PET was employed to evaluate the
      proliferation rate of tumor, and it was compared with that observed from
      [(18)F]FDG/[(18)F]fluoroacetate PET. The expression of proliferating cell nuclear
      antigen (PCNA) in tumor during treatment was determined by semiquantitative
      analysis of immunohistochemical staining. RESULTS: A significant inhibition
      (p<0.001) in tumor growth was observed on day 3 after a single dose treatment.
      The tumor-to-muscle ratio (T/M) derived from [(18)F]FMAU-PET images of lipo-VNB
      treated group declined from 2.33 +/- 0.16 to 1.26 +/- 0.03 after three doses of
      treatment, while that of the control remained steady. The retarded proliferation
      rate of lipo-VNB-treated sarcoma was confirmed by PCNA immunohistochemistry
      staining. However, both [(18)F]FDG and [(18)F]fluoroacetate microPET imaging did
      not show significant difference in T/M between the therapeutic and the control
      groups throughout the entire experimental period. CONCLUSION: Lipo-VNB can
      effectively impede the growth of NG4TL4 sarcoma. [(18)F]FMAU PET is an
      appropriate modality for early monitoring of the tumor response during the
      treatment course of lipo-VNB.

PMID- 23969085
TI  - Synthesis and radiopharmacological evaluation of a high-affinity and
      metabolically stabilized 18F-labeled bombesin analogue for molecular imaging of
      gastrin-releasing peptide receptor-expressing prostate cancer.
AB  - INTRODUCTION: Bombesin (BBN) and BBN analogues have attracted much attention as
      high-affinity ligands for selective targeting of the gastrin-releasing peptide
      (GRP) receptor. GRP receptors are overexpressed in a variety of human cancers
      including prostate cancer. Radiolabeled BBN derivatives are promising diagnostic
      probes for molecular imaging of GRP receptor-expressing prostate cancer. This
      study describes the synthesis and radiopharmacological evaluation of various
      metabolically stabilized fluorobenzoylated bombesin analogues (BBN-1, BBN-2, BBN
      3). METHODS: Three fluorobenzoylated BBN analogues containing an aminovaleric
      (BBN-1, BBN-2), or an aminooctanoic acid linker (BBN-3) were tested in a
      competitive binding assay against (125)I-[Tyr(4)]-BBN for their binding potency
      to the GRP receptor. Intracellular calcium release in human prostate cancer cells
      (PC3) was measured to determine agonistic or antagonistic profiles of
      fluorobenzoylated BBN derivatives. Bombesin derivative BBN-2 displayed the
      highest inhibitory potency toward GRP receptor (IC50 = 8.7 +/- 2.2 nM) and was
      subsequently selected for radiolabeling with fluorine-18 ((18)F) through
      acylation with N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). The
      radiopharmacological profile of (18)F-labeled bombesin [(18)F]BBN-2 was evaluated
      in PC3 tumor-bearing NMRI nude mice involving metabolic stability studies,
      biodistribution experiments and dynamic small-animal PET studies. RESULTS: All
      fluorobenzoylated BBN derivatives displayed high inhibitory potency toward the
      GRP receptor (IC50=8.7-16.7 nM), and all compounds exhibited antagonistic
      profiles as determined in an intracellular calcium release assay. The (18)F
      labeled BBN analogue [(18)F]BBN-2 was obtained in 30% decay-corrected
      radiochemical yield with high radiochemical purity >95% after semi-preparative
      HPLC purification. [(18)F]BBN-2 showed high metabolic stability in vivo with 65%
      of the radiolabeled peptide remaining intact after 60 min p.i. in mouse plasma.
      Biodistribution experiments and dynamic small-animal PET studies demonstrated
      high tumor uptake of [(18)F]BBN-2 in PC3 xenografts (2.75 +/- 1.82 %ID/g after 5
      min and 2.45 +/- 1.25 %ID/g after 60 min p.i.). Specificity of radiotracer uptake
      in PC3 tumors was confirmed by blocking experiments. CONCLUSION: The present
      study demonstrates that (18)F-labeled BBN analogue [(18)F]BBN-2 is a suitable PET
      radiotracer with favorable metabolic stability in vivo for molecular imaging of
      GRP receptor-positive prostate cancer.

PMID- 23969086
TI  - Development of a 13C-optimized 1.5-mm high temperature superconducting NMR probe.
AB  - We report a 1.5-mm NMR probe based on high temperature superconductors operating
      at 14.1T optimized for (13)C detection. The probe has a total sample volume of
      about 35 microliters (MUL) with an active volume of 20 MUL and provides
      exceptional mass sensitivity for (13)C detection. The probe also has excellent
      (1)H sensitivity and employs a (2)H lock; (15)N irradiation capability can be
      added in the future. The coils are cooled to about 20K using a standard Agilent
      cryogenic refrigeration system, and the sample temperature is regulated near room
      temperature. The coil design considerations are discussed in detail. This probe
      is ideal for directly detected (13)C NMR experiments for natural products
      chemistry and metabolomics applications, for which 35 MUL is an optimal sample
      volume. The outstanding (13)C sensitivity of this probe allowed us to directly
      determine the (13)C connectivity on 1.1mg of natural abundance histidine using an
      INADEQUATE experiment. We demonstrated the utility of this probe for (13)C-based
      metabolomics using a synthetic mixture of common natural abundance metabolites
      whose concentrations ranged from 1 to 5mM (40-200 nmol).

PMID- 23969087
TI  - Enzootic and epizootic rabies associated with vampire bats, peru.
AB  - During the past decade, incidence of human infection with rabies virus (RABV)
      spread by the common vampire bat (Desmodus rotundus) increased considerably in
      South America, especially in remote areas of the Amazon rainforest, where these
      bats commonly feed on humans. To better understand the epizootiology of rabies
      associated with vampire bats, we used complete sequences of the nucleoprotein
      gene to infer phylogenetic relationships among 157 RABV isolates collected from
      humans, domestic animals, and wildlife, including bats, in Peru during 2002-2007.
      This analysis revealed distinct geographic structuring that indicates that RABVs
      spread gradually and involve different vampire bat subpopulations with different
      transmission cycles. Three putative new RABV lineages were found in 3 non-vampire
      bat species that may represent new virus reservoirs. Detection of novel RABV
      variants and accurate identification of reservoir hosts are critically important
      for the prevention and control of potential virus transmission, especially to
      humans.

PMID- 23969088
TI  - The contribution of apathy and increased learning trials to risky decision-making
      in Parkinson's disease.
AB  - Impairments in executive functioning are commonly found in Parkinson's disease
      (PD); however, the research into risky decision making has been mixed. The
      present study sought to investigate three potential hypotheses: difficulty
      learning the task probabilities, levodopa equivalent dose (LED), and the presence
      of apathy. Twenty-four individuals with idiopathic PD and 13 healthy controls
      completed the Frontal Systems Behavior Scale to assess current apathy, the Iowa
      Gambling Task, and the Balloon Analog Risk Task (BART). Results indicated that
      individuals with PD selected more from Deck B, a disadvantageous deck. However,
      with an additional set of trials, participants with PD and apathy selected more
      from the most risky deck (Deck A). Apathy was not related to the BART, and LED
      was not related to either task. Results indicate that apathy is associated with
      decision-making in PD, and providing additional learning trials can improve
      decision-making in PD without apathy. 

PMID- 23969089
TI  - The Institute of Medicine Report on the Mental Health and Substance Use Workforce
      for Older Adults: a reflection.

PMID- 23969090
TI  - Delirium in the acute phase after stroke and the role of the apolipoprotein E
      gene.
AB  - OBJECTIVE: To study the association between the epsilon 4 allele of
      apolipoprotein E (APOEepsilon4) and delirium in a stroke population. METHODS: 527
      consecutive stroke patients were screened for delirium during the first week of
      admission with the confusion assessment method. In three hundred fifty-three
      patients genomic DNA isolation was available. RESULTS: The incidence of delirium
      after stroke in the 353 patients was 11.3%. There was no association between
      APOEepsilon4 and delirium. Even after adjustment for IQCODE, stroke localization,
      stroke subtype, stroke severity, infection, and brain atrophy no association was
      found (odds ratio: 0.9; 95% confidence interval: 0.4-2.1). Delirium did not last
      longer in patients with an APOEepsilon4 allele compared to patients without an
      APOEepsilon4 allele (median: 5.6 days [range: 1-21] versus median: 4.6 days
      [range: 1-15], p = 0.5). CONCLUSION: There was no association between the
      presence of an APOEepsilon4 allele and the occurrence of delirium in the acute
      phase after stroke.

PMID- 23969091
TI  - [Bilateral 23Na MR imaging of the breast and quantification of sodium
      concentration].
AB  - A novel setup for (23)Na MRI, which allows bilateral imaging of the breast, is
      presented. For this purpose a figure-eight receive-only (23)Na surface coil was
      developed. For our experiments on three samples with NaCl solutions of different
      sodium concentrations and two female subjects we used an asymmetric birdcage coil
      in transmit mode and the developed surface coil for receiving the signal at 3T.
      Imaging of the samples showed the applicability of the employed normalization
      method for measuring the distribution of sodium concentration. In a sample of
      concentration [Na(+)]=51mM we achieved SNR=70 at a nominal isotropic resolution
      of 2,5mm (TR=66ms, TE=0,6ms, TA=20min). Furthermore we showed that by means of
      this setup it is possible to quantify the sodium concentration in breast tissue
      (TSC) of a female subject with an accuracy of 23% (TR=150ms, TE=0,5ms, TA=45min).

PMID- 23969092
TI  - A quantitative comparison of the performance of three deformable registration
      algorithms in radiotherapy.
AB  - We present an evaluation of various non-rigid registration algorithms for the
      purpose of compensating interfractional motion of the target volume and organs at
      risk areas when acquiring CBCT image data prior to irradiation. Three different
      deformable registration (DR) methods were used: the Demons algorithm implemented
      in the iPlan Software (BrainLAB AG, Feldkirchen, Germany) and two custom
      developed piecewise methods using either a Normalized Correlation or a Mutual
      Information metric (featureletNC and featureletMI). These methods were tested on
      data acquired using a novel purpose-built phantom for deformable registration and
      clinical CT/CBCT data of prostate and lung cancer patients. The Dice similarity
      coefficient (DSC) between manually drawn contours and the contours generated by a
      derived deformation field of the structures in question was compared to the
      result obtained with rigid registration (RR). For the phantom, the piecewise
      methods were slightly superior, the featureletNC for the intramodality and the
      featureletMI for the intermodality registrations. For the prostate cases in less
      than 50% of the images studied the DSC was improved over RR. Deformable
      registration methods improved the outcome over a rigid registration for lung
      cases and in the phantom study, but not in a significant way for the prostate
      study. A significantly superior deformation method could not be identified. 

PMID- 23969094
TI  - Epithelial-to-mesenchymal transition in endometrioid adenocarcinoma of the
      endometrium.

PMID- 23969093
TI  - Inactivation of the lateral habenula reduces anxiogenic behavior and cocaine
      seeking under conditions of heightened stress.
AB  - Recent anatomical and functional studies have renewed interest in the lateral
      habenula (LHb), a critical brain region that works in an opponent manner to
      modulate aversive and appetitive processes. In particular, increased LHb
      activation is believed to drive anxiogenic states during stressful conditions.
      Here, we reversibly inactivated the LHb with GABA receptor agonists
      (baclofen/muscimol) in rats prior to testing in an open field, elevated plus
      maze, and defensive burying task in the presence or absence of yohimbine, a
      noradrenergic alpha2-receptor antagonist that acts as an anxiogenic stressor. In
      a second set of experiments using a cocaine self-administration and reinstatement
      model, we inactivated the LHb during extinction responding and cue-induced
      reinstatement of cocaine seeking in the presence or absence of yohimbine
      pretreatment. Inactivation of the LHb after yohimbine treatment attenuated
      anxiogenic behavior by increasing time spent in the open arms and reducing the
      time spent burying. Inactivation of the LHb also reduced cocaine seeking when cue
      induced reinstatement occurred in the presence of yohimbine, but did not affect
      extinction responding or cue-induced reinstatement by itself. These data
      demonstrate that the LHb critically regulates states of heightened anxiety during
      both unconditioned behavior and conditioned appetitive processes. 

PMID- 23969095
TI  - Claudin-7 expression and its association with tumor progression in systemic
      malignancies.

PMID- 23969096
TI  - Epithelial-to-mesenchymal transition in endometrioid adenocarcinoma of the
      endometrium--reply.

PMID- 23969097
TI  - Left-sided sessile serrated polyps/adenomas.

PMID- 23969098
TI  - Left-sided sessile serrated polyps/adenomas--reply.

PMID- 23969099
TI  - Papillary thyroid microcarcinoma associated with metastasis and fatal outcome: is
      the microcarcinoma an incidental finding?

PMID- 23969100
TI  - Papillary thyroid microcarcinoma associated with metastasis and fatal outcome: is
      the microcarcinoma an incidental finding?--reply.

PMID- 23969102
TI  - Transparent nanocrystalline yttria-stabilized-zirconia calvarium prosthesis.
AB  - Laser-based diagnostics and therapeutics show promise for many neurological
      disorders. However, the poor transparency of cranial bone (calvaria) limits the
      spatial resolution and interaction depth that can be achieved, thus constraining
      opportunity in this regard. Herein, we report preliminary results from efforts
      seeking to address this limitation through use of novel transparent cranial
      implants made from nanocrystalline yttria-stabilized zirconia (nc-YSZ). Using
      optical coherence tomography (OCT) imaging of underlying brain in an acute murine
      model, we show that signal strength is improved when imaging through nc-YSZ
      implants relative to native cranium. As such, this provides initial evidence
      supporting the feasibility of nc-YSZ as a transparent cranial implant material.
      Furthermore, it represents a crucial first step towards realization of an
      innovative new concept we are developing, which seeks to eventually provide a
      clinically-viable means for optically accessing the brain, on-demand, over large
      areas, and on a chronically-recurring basis, without need for repeated
      craniectomies. FROM THE CLINICAL EDITOR: In this study, transparent
      nanocrystalline yttria-stabilized-zirconia is used as an experimental "cranium
      prosthesis" material, enabling the replacement of segments of cranial bone with a
      material that allows for optical access to the brain on a recurrent basis using
      optical imaging methods such as OCT.

PMID- 23969101
TI  - A novel liposomal formulation of FTY720 (fingolimod) for promising enhanced
      targeted delivery.
AB  - We describe here the development and characterization of the physicochemical and
      pharmacokinetic properties of a novel liposomal formulation for FTY720 delivery,
      LP-FTY720. The mean diameter of LP-FTY720 was ~157 nm, and the FTY720 entrapment
      efficiency was ~85%. The liposomal formulation protected FTY720 from degradation
      in aqueous buffer and showed toxicity in CLL patient B cells comparable to that
      of free FTY720. Following intravenous injection in ICR mice, LP-FTY720 had an
      increased elimination phase half-life (~28 vs. ~19 hr) and decreased clearance
      (235 vs. 778 mL/h/kg) compared to the free drug. Antibodies against CD19, CD20
      and CD37 were incorporated into LP-FTY720, which provided targeted delivery to
      CLL patient B cells and thus achieved higher killing efficacy. The novel
      liposomal carrier of FTY720 demonstrated improved pharmacokinetic properties,
      comparable activity, and a potential platform for targeted delivery to CLL by
      overcoming the limited application of free FTY720 to B malignancy treatment. FROM
      THE CLINICAL EDITOR: This team reports on a novel liposomal formulation for
      FTY720 delivery, demonstrating improved pharmacokinetic properties, comparable
      activity, and a potential platform for targeted delivery to CLL using antibodies
      incorporated in the liposomes. The method expected to overcome the limited
      application of free FTY720 to B malignancy treatment.

PMID- 23969103
TI  - High loading of hydrophilic/hydrophobic doxorubicin into polyphosphazene
      polymersome for breast cancer therapy.
AB  - Breast cancer remains one of the most common cancers for females. Drug delivery
      based on cancer nanotechnology could improve the performance of some
      chemotherapeutic medicines already used in clinic. The emergence of polymersomes
      provided the potential to encapsulate hydrophobic/hydrophilic drugs. By modifying
      the weight ratio of methoxy-poly (ethylene glycol) (mPEG) chain to ethyl-p
      aminobenzoate (EAB) side group, a series of amphiphilic graft polyphosphazenes
      (PEPs) was prepared. PEP can be tuned from micelles to polymersomes with the
      decrease of mPEG content via dialysis. Either hydrophilic doxorubicin
      hydrochloride (DOX.HCl) or hydrophobic doxorubicin base (DOX) could be
      encapsulated into PEP polymersomes with high payload and high encapsulation
      efficiency due to the strong intermolecular interaction with PEP. Compared with
      free DOX.HCl administration, in vivo investigation in growth inhibition of MCF-7
      xenograft tumors in nude mice demonstrated that PEP polymersomes could enhance
      life safety without compromise of therapeutic efficacy, especially DOX.HCl loaded
      delivery system. FROM THE CLINICAL EDITOR: In this preclinical study,
      polymerosomes based on PEPs were investigated as doxorubicin delivery systems,
      demonstrating similar efficacy but less toxicity compared to standard delivery
      methods.

PMID- 23969104
TI  - A novel polyethylene glycol mediated lipid nanoemulsion as drug delivery carrier
      for paclitaxel.
AB  - A novel polyethylene glycol 400 (PEG400) mediated lipid nanoemulsion as drug
      delivery carrier for paclitaxel (PTX) was successfully developed. The formulation
      comprised a PEG400 solution of the drug (25mg/mL) that would be mixed with
      commercially 20% lipid emulsion to form PTX-loaded nanoemulsion (1mg/mL) prior to
      use. This two-vial formulation of PTX-loaded lipid nanoemulsion (TPLE) could
      significantly reduce extraction of reticuloendothelial system (RES) organs and
      increase tumor uptake, and exhibited more potent antitumor efficacy on bearing
      A2780 or Bcap-37 tumor nude mice compared to conventional PTX-loaded lipid
      nanoemulsion (CPLE). TPLE did not cause haematolysis and intravenous irritation
      response yet, and showed the same cytotoxicity against HeLa cells as Taxol(r),
      and its LD50 was 2.7-fold higher than that of Taxol(r), suggesting its good
      safety and druggability. In addition, TPLE displayed distinctly faster release of
      PTX, a greater proportion of PTX in phospholipids layer and a smaller share in
      oil phase than CPLE. From the Clinical Editor: This study demonstrates the
      feasibility and potential advantage of a novel PEG400-mediated two-vial
      formulation of lipid nanoemulsion as drug carrier for PTX in clinical application
      for the cancer therapy. FROM THE CLINICAL EDITOR: This team of investigators
      convincingly demonstrates the feasibility and potential advantage of a PEG400
      mediated two-vial formulation of lipid nanoemulsion as drug carrier for PTX in
      cancer therapy, documenting superior safety and faster release of PTX compared to
      commercially available formulations.

PMID- 23969105
TI  - Parallel microfluidic synthesis of size-tunable polymeric nanoparticles using 3D
      flow focusing towards in vivo study.
AB  - Microfluidic synthesis of nanoparticles (NPs) can enhance the controllability and
      reproducibility in physicochemical properties of NPs compared to bulk synthesis
      methods. However, applications of microfluidic synthesis are typically limited to
      in vitro studies due to low production rates. Herein, we report the
      parallelization of NP synthesis by 3D hydrodynamic flow focusing (HFF) using a
      multilayer microfluidic system to enhance the production rate without losing the
      advantages of reproducibility, controllability, and robustness. Using parallel 3D
      HFF, polymeric poly(lactide-co-glycolide)-b-polyethyleneglycol (PLGA-PEG) NPs
      with sizes tunable in the range of 13-150 nm could be synthesized reproducibly
      with high production rate. As a proof of concept, we used this system to perform
      in vivo pharmacokinetic and biodistribution study of small (20 nm diameter) PLGA
      PEG NPs that are otherwise difficult to synthesize. Microfluidic parallelization
      thus enables synthesis of NPs with tunable properties with production rates
      suitable for both in vitro and in vivo studies. FROM THE CLINICAL EDITOR:
      Applications of nanoparticle synthesis with microfluidic methods are typically
      limited to in vitro studies due to low production rates. The team of authors of
      this proof-of-principle study reports on the successful parallelization of NP
      synthesis by 3D hydrodynamic flow focusing using a multilayer microfluidic system
      to enhance production rate without losing the advantages of reproducibility,
      controllability, and robustness.

PMID- 23969106
TI  - Steroidal saponins from the flowers of Dioscorea bulbifera var. sativa.
AB  - Eleven steroidal saponins, dioscoreanosides A-K, along with five known congeners,
      were isolated from the flowers of Dioscorea bulbifera var. sativa. Their
      structures were established by extensive NMR experiments in conjunction with mass
      spectrometry. The isolated compounds were tested for cytotoxicity against urinary
      bladder carcinoma cells (ECV-304 cells). Our results revealed a moderate activity
      for spiroconazol A (15), pennogenin 3-O-alpha-l-rhamnopyranosyl-(1->4)-alpha-l
      rhamnopyranosyl-(1->4)-[alpha-l-rhamnopyranosyl-(1->2)]-beta-d-glucopyranoside
      (12), and 26-O-beta-d-glucopyranosyl-(25R)-5-en-furost-3beta,17alpha,22alpha,26
      tetraol-3-O-alpha-l-rhamnopyranosyl-(1->4)-alpha-l-rhamnopyranosyl-(1->4)-[alpha
      l-rhamnopyranosyl-(1->2)]-beta-d-glucopyranoside (13). 

PMID- 23969107
TI  - Cohaerins G-K, azaphilone pigments from Annulohypoxylon cohaerens and absolute
      stereochemistry of cohaerins C-K.
AB  - Four azaphilones, for which the trivial names cohaerins G, H, I and K are
      proposed, were isolated from the methanolic stromatal extract of Annulohypoxylon
      cohaerens together with the known metabolites cohaerins C-F and 4,5,4',5'
      tetrahydroxy-1,1'-binaphthyl (BNT). Their planar structures were determined by
      NMR spectroscopy and by mass spectrometry. While their core structure is
      identical with cohaerin C and F, respectively, subgroups 2-hydroxy-6-methylphenyl
      and (1R,2R,4S)-4-hydroxy-2-methyl-6-oxocyclohexyl account for the structural
      diversity as substituents at C-3 of the azaphilone core. The absolute
      stereochemistry was assigned by NOE NMR experiments, CD spectroscopy and
      derivatisation with Mosher's acid; in addition, the stereochemistry of cohaerins
      C-F was revised. The metabolites showed cytotoxic effects besides a weak
      antimicrobial activity. 

PMID- 23969108
TI  - Structural and bioinformatic analysis of the kiwifruit allergen Act d 11, a
      member of the family of ripening-related proteins.
AB  - The allergen Act d 11, also known as kirola, is a 17 kDa protein expressed in
      large amounts in ripe green and yellow-fleshed kiwifruit. Ten percent of all
      kiwifruit-allergic individuals produce IgE specific for the protein. Using X-ray
      crystallography, we determined the first three-dimensional structures of Act d
      11, produced from both recombinant expression in Escherichia coli and from the
      natural source (kiwifruit). While Act d 11 is immunologically correlated with the
      birch pollen allergen Bet v 1 and other members of the pathogenesis-related
      protein family 10 (PR-10), it has low sequence similarity to PR-10 proteins. By
      sequence Act d 11 appears instead to belong to the major latex/ripening-related
      (MLP/RRP) family, but analysis of the crystal structures shows that Act d 11 has
      a fold very similar to that of Bet v 1 and other PR-10 related allergens
      regardless of the low sequence identity. The structures of both the natural and
      recombinant protein include an unidentified ligand, which is relatively small
      (about 250 Da by mass spectrometry experiments) and most likely contains an
      aromatic ring. The ligand-binding cavity in Act d 11 is also significantly
      smaller than those in PR-10 proteins. The binding of the ligand, which we were
      not able to unambiguously identify, results in conformational changes in the
      protein that may have physiological and immunological implications.
      Interestingly, the residue corresponding to Glu45 in Bet v 1 (Glu46), which is
      important for IgE binding to the birch pollen allergen, is conserved in Act d 11,
      even though it is not in other allergens with significantly higher sequence
      identity to Bet v 1. We suggest that the so-called Gly-rich loop (or P-loop),
      which is conserved in all PR-10 allergens, may be responsible for IgE cross
      reactivity between Bet v 1 and Act d 11.

PMID- 23969109
TI  - Heme oxygenase-1 induction by the ROS-JNK pathway plays a role in aluminum
      induced anemia.
AB  - Aluminum (Al) overload is correlated with hypochromic anemia. It is possible that
      Al impedes heme biosynthesis and degradation by affecting the activity of
      biosynthetic enzymes. However, the molecular mechanisms by which Al affects these
      enzymes are unknown. Here, we show that long-term exposure of Sprague-Dawley rats
      to Al decreased hemoglobin concentration and the hematocrit level. In addition,
      the activity of aminolevulinic acid dehydratase (ALA-D) in rat liver was reduced,
      but heme oxygenase (HO) activity was enhanced, suggesting an impairment of heme
      homeostasis. The increase in HO activity was due to up-regulation of mRNA and
      protein of an inducible HO isozyme, HO-1. Furthermore, we found that reactive
      oxygen species (ROS)-mediated activation of c-Jun N-terminal kinase (JNK) was
      critical for HO-1 induction by Al, because ROS scavengers and JNK inhibitors
      abrogated enhancement of HO-1 by Al in rat hepatocytes. Thus, Al enhances HO-1
      expression through the ROS-JNK pathway, which may enhance HO activity and
      accelerate degradation of heme, leading to hypochromic anemia.

PMID- 23969111
TI  - Risk factors of fecal carriage with extended-spectrum beta-lactamase-producing
      Enterobacteriaceae in hospitalized patients.
AB  - BACKGROUND: Colonization of multidrug-resistant microorganisms is a potential
      source of cross transmission and subsequent infection. Screening of extended
      spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) is not yet a
      routine practice in most hospitals. METHODS: The purpose of this study was to
      investigate the risk factors of fecal carriage of ESBL-E in hospitalized
      patients. A total of 174 samples (from 97 patients) was collected. Screening test
      was accomplished using commercial chromogenic medium (ChromID ESBL agar;
      bioMerieux, Marcy l'Etoile, France). The presence of ESBLs of grown isolates was
      confirmed by Clinical and Laboratory Standards Institute guidelines. Analysis of
      the risk factors of ESBL-E carriage was performed by multivariate logistic
      regression. RESULTS: Among the risk factors, multivariate analysis demonstrated
      that prolonged hospitalization (>=90 days) (odds ratio [OR], 6.76; 95% confidence
      interval [CI]: 1.17-39.23; P = .033), prolonged intensive care unit stay (>=14
      days) (OR, 4.78; 95% CI: 1.70-13.42; P = .003), and methicillin-resistant
      Staphylococcus aureus carriage (OR, 3.29; 95% CI: 1.20-9.01; P = .020) were found
      to be significantly associated with fecal carriers. CONCLUSION: This study
      clarified the characteristics and the risk factors of hospitalized patients
      carrying ESBL-E. In addition, the cost-benefit of routine screening in addition
      to methicillin-resistant Staphylococcus aureus and vancomycin-resitant
      Enterococci needs to be assessed.

PMID- 23969110
TI  - Bioinformatic analyses of integral membrane transport proteins encoded within the
      genome of the planctomycetes species, Rhodopirellula baltica.
AB  - Rhodopirellula baltica (R. baltica) is a Planctomycete, known to have
      intracellular membranes. Because of its unusual cell structure and ecological
      significance, we have conducted comprehensive analyses of its transmembrane
      transport proteins. The complete proteome of R. baltica was screened against the
      Transporter Classification Database (TCDB) to identify recognizable integral
      membrane transport proteins. 342 proteins were identified with a high degree of
      confidence, and these fell into several different classes. R. baltica encodes in
      its genome channels (12%), secondary carriers (33%), and primary active transport
      proteins (41%) in addition to classes represented in smaller numbers. Relative to
      most non-marine bacteria, R. baltica possesses a larger number of sodium
      dependent symporters but fewer proton-dependent symporters, and it has
      dimethylsulfoxide (DMSO) and trimethyl-amine-oxide (TMAO) reductases, consistent
      with its Na(+)-rich marine environment. R. baltica also possesses a Na(+)
      translocating NADH:quinone dehydrogenase (Na(+)-NDH), a Na(+) efflux
      decarboxylase, two Na(+)-exporting ABC pumps, two Na(+)-translocating F-type
      ATPases, two Na(+):H(+) antiporters and two K(+):H(+) antiporters. Flagellar
      motility probably depends on the sodium electrochemical gradient. Surprisingly,
      R. baltica also has a complete set of H(+)-translocating electron transport
      complexes similar to those present in alpha-proteobacteria and eukaryotic
      mitochondria. The transport proteins identified proved to be typical of the
      bacterial domain with little or no indication of the presence of eukaryotic-type
      transporters. However, novel functionally uncharacterized multispanning membrane
      proteins were identified, some of which are found only in Rhodopirellula species,
      but others of which are widely distributed in bacteria. The analyses lead to
      predictions regarding the physiology, ecology and evolution of R. baltica. 

PMID- 23969113
TI  - A prospective, randomized, controlled trial of the efficacy and safety of fibrin
      pad as an adjunct to control soft tissue bleeding during abdominal,
      retroperitoneal, pelvic, and thoracic surgery.
AB  - BACKGROUND: This study evaluated the hemostatic effectiveness and safety of
      Fibrin Pad (Omrix Biopharmaceuticals Ltd.) vs absorbable hemostat in patients
      undergoing nonemergent surgery. Fibrin Pad is a topical absorbable hemostat
      designed to be effective in a variety of soft tissues and across multiple
      bleeding intensities. STUDY DESIGN: Patients 18 years and older, requiring
      abdominal, retroperitoneal, pelvic, or thoracic (noncardiac) surgery and with an
      appropriate soft-tissue target bleeding site (TBS), were randomized to receive
      Fibrin Pad or absorbable hemostat (NCT00658723). Patients were stratified by
      bleeding severity at the TBS. Assessments included percentage of patients
      achieving hemostasis at 4 minutes after randomization with no rebleeding
      requiring treatment during the subsequent 6 minutes (primary endpoint),
      proportion of patients achieving hemostasis at 10 minutes, and incidence of
      treatment failure. RESULTS: On the primary endpoint, 98.3% of patients with
      Fibrin Pad and 53.3% with absorbable hemostat achieved hemostasis at 4 minutes (p
      < 0.0001). The treatment differential was magnified (efficacy was maintained with
      Fibrin Pad but decreased with absorbable hemostat) with increasing bleeding
      intensity: in patients with mild bleeding, 100.0% vs 80.0% achieved hemostasis
      with Fibrin Pad and absorbable hemostat (p = 0.03), respectively; rates were
      96.6% vs 26.7%, respectively (p < 0.0001) with moderate bleeding. Percentages of
      patients who achieved hemostasis at 10 minutes were: Fibrin Pad, 98.3% and
      absorbable hemostat, 73.3% (p < 0.0001). Incidences of adverse events were
      comparable between groups. CONCLUSIONS: Fibrin Pad is superior to absorbable
      hemostat (SURGICEL Original Absorbable Hemostat [Ethicon]) in soft-tissue
      bleeding control and is safe and effective as an adjunct for rapidly and reliably
      achieving hemostasis for soft-tissue bleeding during surgery.

PMID- 23969114
TI  - Adherence of randomized trials within children's surgical specialties published
      during 2000 to 2009 to standard reporting guidelines.
AB  - BACKGROUND: Randomized clinical trials (RCTs) are uncommon in pediatric surgical
      specialties and the quality of reporting is unknown. Our primary purpose was to
      analyze published surgical RCTs involving children to measure adherence to the
      Consolidated Standards of Reporting Trials (CONSORT) guidelines. STUDY DESIGN:
      Published RCTs from January 1, 2000 through December 31, 2009 were reviewed. The
      trials were evaluated for the presence of 7 CONSORT guidelines and also graded
      according to the Jadad scale. RESULTS: Two hundred and twenty-eight trials were
      included. Five trials met all 7 CONSORT criteria (2%) and 53 had a Jadad score of
      >=3 (23%). Slightly more than 50% of all trials specified primary outcomes and
      <25% described power calculations according to CONSORT. Adherence to CONSORT
      guidelines for allocation concealment, randomization description, and attrition
      details was even lower. There were significant differences between surgical
      specialties with regard to CONSORT adherence to the majority of the guidelines.
      Pediatric general surgery had the largest number of published RCTs. Pediatric
      orthopaedic surgery had the highest proportion of trials with a Jadad score >=3
      (40%). CONCLUSIONS: Adherence to CONSORT guidelines is low across the spectrum of
      children's surgical specialties, although significant differences do exist.
      Future RCTs in children's surgical specialties should specifically focus on areas
      of low adherence to reporting guidelines.

PMID- 23969112
TI  - Thiocyanate potentiates antimicrobial photodynamic therapy: in situ generation of
      the sulfur trioxide radical anion by singlet oxygen.
AB  - Antimicrobial photodynamic therapy (PDT) is used for the eradication of
      pathogenic microbial cells and involves the light excitation of dyes in the
      presence of O2, yielding reactive oxygen species including the hydroxyl radical
      (OH) and singlet oxygen ((1)O2). In order to chemically enhance PDT by the
      formation of longer-lived radical species, we asked whether thiocyanate (SCN(-))
      could potentiate the methylene blue (MB) and light-mediated killing of the gram
      positive Staphylococcus aureus and the gram-negative Escherichia coli. SCN(-)
      enhanced PDT (10 uM MB, 5 J/cm(2) 660 nm hv) killing in a concentration-dependent
      manner of S. aureus by 2.5 log10 to a maximum of 4.2 log10 at 10mM (P<0.001) and
      increased killing of E. coli by 3.6 log10 to a maximum of 5.0 log10 at 10mM
      (P<0.01). We determined that SCN(-) rapidly depleted O2 from an irradiated MB
      system, reacting exclusively with (1)O2, without quenching the MB excited triplet
      state. SCN(-) reacted with (1)O2, producing a sulfur trioxide radical anion (a
      sulfur-centered radical demonstrated by EPR spin trapping). We found that MB-PDT
      of SCN(-) in solution produced both sulfite and cyanide anions, and that addition
      of each of these salts separately enhanced MB-PDT killing of bacteria. We were
      unable to detect EPR signals of OH, which, together with kinetic data, strongly
      suggests that MB, known to produce OH and (1)O2, may, under the conditions used,
      preferentially form (1)O2.

PMID- 23969115
TI  - Does the size of the stitch length affect surgical site infection?

PMID- 23969116
TI  - Pancreatic duct ligation: an idea revisited.

PMID- 23969117
TI  - Trends in attrition rates for surgical faculty.

PMID- 23969119
TI  - Toll-like receptor 4 is involved in myocardial damage following paraquat
      poisoning in mice.
AB  - The ingestion of the herbicide paraquat (PQ) can cause multiple organ injury
      including cardiac lesions. However, the underlying mechanism of myocardial damage
      is not known. Toll-like receptor 4 (TRL4) is a pattern-recognition receptor in
      the innate immune response to microbial pathogens. TLR4 is involved in heart
      dysfunction such as septic shock or myocardial ischemia. We investigated whether
      TLR4 would be linked to the pathogenesis of heart disease due to PQ exposure.
      Wild type mice (WT) and TLR4-deficient mice were injected intraperitoneally with
      75mg/kg of PQ to induce myocardial damage and tested for echocardiographic
      assessment, histopathology, pro-inflammatory cytokine and TLR4 expression. WT
      mice after PQ exposure displayed deteriorate cardiac function, pathological
      damages, increased TLR4 mRNA and protein levels as well as myocardial TNF-alpha
      and IL-1beta levels. Compared with WT mice, TLR4-deficient mice were
      significantly resistant to the PQ-induced injury. We concluded that the TLR4 was
      required as a mediator and played an important role in myocardial damage due to
      PQ. 

PMID- 23969120
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces microglial nitric oxide
      production and subsequent rat primary cortical neuron apoptosis through p38/JNK
      MAPK pathway.
AB  - It has been widely accepted that microglia, which are the innate immune cells in
      the brain, upon activation can cause neuronal damage. In the present study, we
      investigated the role of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in regulating
      microglial nitric oxide production and its role in causing neuronal damage. The
      study revealed that TCDD stimulates the expression of inducible nitric oxide
      synthase (iNOS) as well as the production of nitric oxide (NO) in a dose- and
      time-dependent manner. Further, a rapid activation of p38 and JNK MAPKs was found
      in HAPI microglia following TCDD treatment. Blockage of p38 and JNK kinases with
      their specific inhibitors, SB202190 and SP600125, significantly reduced TCDD
      induced iNOS expression and NO production. In addition, it was demonstrated
      through treating rat primary cortical neurons with media conditioned with TCDD
      treated microglia that microglial iNOS activation mediates neuronal apoptosis.
      Lastly, it was also found that p38 and JNK MAPK inhibitors could attenuate the
      apoptosis of rat cortical neurons upon exposure to medium conditioned by TCDD
      treated HAPI microglial cells. Based on these observations, we highlight that the
      p38/JNK MAPK pathways play an important role in TCDD-induced iNOS activation in
      rat HAPI microglia and in the subsequent induction of apoptosis in primary
      cortical neurons. 

PMID- 23969121
TI  - How NOD2 and autophagy may be related to Crohn's disease? A view shifted from
      live microbes to luminal bacterial debris.

PMID- 23969123
TI  - Journal performance report for 2012.

PMID- 23969124
TI  - A woman's secret. Filler rhinoplasty with Radiesse (Merz Aesthetics, San Mateo,
      CA) and gold thread implantation.

PMID- 23969125
TI  - Commentary.

PMID- 23969122
TI  - From tissue mechanics to transcription factors.
AB  - Changes in tissue stiffness are frequently associated with diseases such as
      cancer, fibrosis, and atherosclerosis. Several recent studies suggest that, in
      addition to resulting from pathology, mechanical changes may play a role akin to
      soluble factors in causing the progression of disease, and similar mechanical
      control might be essential for normal tissue development and homeostasis. Many
      cell types alter their structure and function in response to exogenous forces or
      as a function of the mechanical properties of the materials to which they adhere.
      This review summarizes recent progress in identifying intracellular signaling
      pathways, and especially transcriptional programs, that are differentially
      activated when cells adhere to materials with different mechanical properties or
      when they are subject to tension arising from external forces. Several
      cytoplasmic or cytoskeletal signaling pathways involving small GTPases, focal
      adhesion kinase and transforming growth factor beta as well as the
      transcriptional regulators MRTF-A, NFkappaB, and Yap/Taz have emerged as
      important mediators of mechanical signaling. 

PMID- 23969126
TI  - Change of shift. Nothing personal.

PMID- 23969127
TI  - Annals of Emergency Medicine Journal Club. Treatment of calcium channel blocker
      poisoning: should we re-prioritize our potpourri of treatment options?

PMID- 23969128
TI  - Female with rash. Cutaneous tattoo reaction.

PMID- 23969129
TI  - PECARN abdominal injury rule should exclude potentially abused children.

PMID- 23969130
TI  - In reply.

PMID- 23969131
TI  - A case of delayed sequence intubation in a pediatric patient with respiratory
      syncytial virus.

PMID- 23969132
TI  - Plasmodium falciparum mutant haplotype infection during pregnancy associated with
      reduced birthweight, Tanzania.
AB  - Intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine
      (IPTp-SP) is a key strategy in the control of pregnancy-associated malaria.
      However, this strategy is compromised by widespread drug resistance from single
      nucleotide polymorphisms in the Plasmodium falciparum dihydrofolate reductase and
      dihydropteroate synthetase genes. During September 2008-October 2010, we
      monitored a cohort of 924 pregnant women in an area of Tanzania with declining
      malaria transmission. P. falciparum parasites were genotyped, and the effect of
      infecting haplotypes on birthweight was assessed. Of the genotyped parasites,
      9.3%, 46.3%, and 44.4% had quadruple or less, quintuple, and sextuple mutated
      haplotypes, respectively. Mutant haplotypes were unrelated to SP doses. Compared
      with infections with the less-mutated haplotypes, infections with the sextuple
      haplotype mutation were associated with lower (359 g) birthweights. Continued use
      of the suboptimal IPTp-SP regimen should be reevaluated, and alternative
      strategies (e.g., intermittent screening and treatment or intermittent treatment
      with safe and effective alternative drugs) should be evaluated.

PMID- 23969133
TI  - MLML: consistent simultaneous estimates of DNA methylation and
      hydroxymethylation.
AB  - MOTIVATION: The two major epigenetic modifications of cytosines, 5-methylcytosine
      (5-mC) and 5-hydroxymethylcytosine (5-hmC), coexist with each other in a range of
      mammalian cell populations. Increasing evidence points to important roles of 5
      hmC in demethylation of 5-mC and epigenomic regulation in development. Recently
      developed experimental methods allow direct single-base profiling of either 5-hmC
      or 5-mC. Meaningful analyses seem to require combining these experiments with
      bisulfite sequencing, but doing so naively produces inconsistent estimates of 5
      mC or 5-hmC levels. RESULTS: We present a method to jointly model read counts
      from bisulfite sequencing, oxidative bisulfite sequencing and Tet-Assisted
      Bisulfite sequencing, providing simultaneous estimates of 5-hmC and 5-mC levels
      that are consistent across experiment types. AVAILABILITY:
      http://smithlab.usc.edu/software/mlml

PMID- 23969134
TI  - Bayesian Network Webserver: a comprehensive tool for biological network modeling.
AB  - SUMMARY: The Bayesian Network Webserver (BNW) is a platform for comprehensive
      network modeling of systems genetics and other biological datasets. It allows
      users to quickly and seamlessly upload a dataset, learn the structure of the
      network model that best explains the data and use the model to understand
      relationships between network variables. Many datasets, including those used to
      create genetic network models, contain both discrete (e.g. genotype) and
      continuous (e.g. gene expression traits) variables, and BNW allows for modeling
      hybrid datasets. Users of BNW can incorporate prior knowledge during structure
      learning through an easy-to-use structural constraint interface. After structure
      learning, users are immediately presented with an interactive network model,
      which can be used to make testable hypotheses about network relationships.
      AVAILABILITY AND IMPLEMENTATION: BNW, including a downloadable structure learning
      package, is available at http://compbio.uthsc.edu/BNW. (The BNW interface for
      adding structural constraints uses HTML5 features that are not supported by
      current version of Internet Explorer. We suggest using other browsers (e.g.
      Google Chrome or Mozilla Firefox) when accessing BNW). CONTACT: ycui2@uthsc.edu.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 23969135
TI  - DNorm: disease name normalization with pairwise learning to rank.
AB  - MOTIVATION: Despite the central role of diseases in biomedical research, there
      have been much fewer attempts to automatically determine which diseases are
      mentioned in a text-the task of disease name normalization (DNorm)-compared with
      other normalization tasks in biomedical text mining research. METHODS: In this
      article we introduce the first machine learning approach for DNorm, using the
      NCBI disease corpus and the MEDIC vocabulary, which combines MeSH(r) and OMIM.
      Our method is a high-performing and mathematically principled framework for
      learning similarities between mentions and concept names directly from training
      data. The technique is based on pairwise learning to rank, which has not
      previously been applied to the normalization task but has proven successful in
      large optimization problems for information retrieval. RESULTS: We compare our
      method with several techniques based on lexical normalization and matching,
      MetaMap and Lucene. Our algorithm achieves 0.782 micro-averaged F-measure and
      0.809 macro-averaged F-measure, an increase over the highest performing baseline
      method of 0.121 and 0.098, respectively. AVAILABILITY: The source code for DNorm
      is available at http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/DNorm, along with
      a web-based demonstration and links to the NCBI disease corpus. Results on PubMed
      abstracts are available in PubTator:
      http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/PubTator .

PMID- 23969136
TI  - Genome compression: a novel approach for large collections.
AB  - MOTIVATION: Genomic repositories are rapidly growing, as witnessed by the 1000
      Genomes or the UK10K projects. Hence, compression of multiple genomes of the same
      species has become an active research area in the past years. The well-known
      large redundancy in human sequences is not easy to exploit because of huge memory
      requirements from traditional compression algorithms. RESULTS: We show how to
      obtain several times higher compression ratio than of the best reported results,
      on two large genome collections (1092 human and 775 plant genomes). Our inputs
      are variant call format files restricted to their essential fields. More
      precisely, our novel Ziv-Lempel-style compression algorithm squeezes a single
      human genome to ~400 KB. The key to high compression is to look for similarities
      across the whole collection, not just against one reference sequence, what is
      typical for existing solutions. AVAILABILITY: http://sun.aei.polsl.pl/tgc (also
      as Supplementary Material) under a free license. Supplementary data:
      Supplementary data are available at Bioinformatics online.

PMID- 23969137
TI  - Subtle adjustments of the glucose-6-phosphate dehydrogenase (G6PD) mutation
      database and reference sequence.

PMID- 23969138
TI  - Molecular cloning and expression of TLR in the Eisenia andrei earthworm.
AB  - Toll-like receptors (TLRs) play an important role in defense responses to
      pathogens in invertebrates. Here we characterize the first TLR isolated from an
      oligochaete annelid, namely, Eisenia andrei (EaTLR) and show its expression
      pattern. The full-length EaTLR cDNA consists of 2615 bp encoding a putative
      protein of 675 amino acids. The predicted amino acid sequence comprises of an
      extracellular domain containing 31 amino acid signal peptide and seven leucine
      rich repeats (LRR), capped with cysteine-rich N- and C-terminal LRRs followed by
      a transmembrane domain and cytoplasmic Toll/IL-1R domain (TIR). TIR domains of
      twenty individual earthworms were sequenced and the variability suggesting the
      presence of a high number of TLR genes in the genome of E. andrei was observed.
      Phylogenetic analysis revealed the highest similarity of EaTLR with polychaete
      annelid, Capitella teleta and TLRs of mollusks and echinoderms. Finally, the
      highest constitutive expression of EaTLR was observed in the digestive tract.
      Gene expression was significantly increased in coelomocytes of E. andrei after
      the challenge with Gram-positive bacteria.

PMID- 23969139
TI  - Ergonomics in the operating room: protecting the surgeon.
AB  - STUDY OBJECTIVE: To review elements of an ergonomic operating room environment
      and describe common ergonomic errors in surgeon posture during laparoscopic and
      robotic surgery. DESIGN: Descriptive video based on clinical experience and a
      review of the literature (Canadian Task Force classification III). SETTING:
      Community teaching hospital affiliated with a major teaching hospital.
      SUBJECTS/AUDIENCE: Gynecologic surgeons. INTERVENTION: Demonstration of surgical
      ergonomic principles and common errors in surgical ergonomics by a physical
      therapist and surgeon. MEASUREMENTS AND MAIN RESULTS: The physical nature of
      surgery necessitates awareness of ergonomic principles. The literature has
      identified ergonomic awareness to be grossly lacking among practicing surgeons,
      and video has not been documented as a teaching tool for this population. Taking
      this into account, we created a video that demonstrates proper positioning of
      monitors and equipment, and incorrect and correct ergonomic positions during
      surgery. Also presented are 3 common ergonomic errors in surgeon posture: forward
      head position, improper shoulder elevation, and pelvic girdle asymmetry. Postural
      reset and motion strategies are demonstrated to help the surgeon learn techniques
      to counterbalance the sustained and awkward positions common during surgery that
      lead to muscle fatigue, pain, and degenerative changes. CONCLUSION: Correct
      ergonomics is a learned and practiced behavior. We believe that video is a useful
      way to facilitate improvement in ergonomic behaviors. We suggest that
      consideration of operating room setup, proper posture, and practice of postural
      resets are necessary components for a longer, healthier, and pain-free surgical
      career.

PMID- 23969140
TI  - Double circular stapler technique for bowel resection in rectosigmoid
      endometriosis.
AB  - To reduce bladder function impairment and avert the serious complications of
      anastomotic leakage after segmental rectosigmoidectomy and to minimize the
      persistence of endometriotic lesions associated with discoid resection, we used
      the double circular stapling (DCS) technique. This technique enables excision of
      bowel endometriosis nodules larger than those that can be removed with the single
      load technique of the circular stapler. Of 120 patients who underwent surgery to
      treat bowel endometriosis, intestinal shaving was performed in 24, discoid
      resection with single circular stapling in 40, and rectosigmoidectomy in 55.
      Eleven patients (9.2%) underwent the DCS technique. In the DCS group, the size of
      the rectosigmoid lesion ranged from 2.2 cm to 4.2 cm. Median operative time for
      the DCS technique was 100 minutes, compared with 150 minutes for
      rectosigmoidectomy (p = .04). Only 1 of 11 patients (9%) had urinary retention,
      compared with postoperative urinary retention in 14 of 55 patients (25%) who had
      undergone rectosigmoidectomy (difference not significant). Only 1 patient, with a
      4.2-cm nodule, had a positive margin in the specimen obtained at the second
      stapling. DCS is a promising technique and may avert rectosigmoidectomy in
      selected patients.

PMID- 23969141
TI  - General or specific factors in the treatment of primary fibromyalgia syndrome?
      Comment to Luyten P. and Abbass A. "What is the evidence for specific factors in
      the psychotherapeutic treatment of fibromyalgia?".

PMID- 23969142
TI  - Sex differences in biopsychosocial correlates of binge eating disorder: a study
      of treatment-seeking obese adults in primary care setting.
AB  - OBJECTIVE: Although community-based studies suggest equivalent levels of physical
      and psychological impairment by binge eating disorder (BED) in men and women, men
      with BED are still underrepresented in clinical studies. This study aimed to
      provide a comprehensive analysis of sex differences in biopsychosocial correlates
      of treatment-seeking obese patients with BED in primary care. METHOD: One hundred
      ninety obese adults (26% men) were recruited in primary care settings for a
      treatment study for obesity and BED. RESULTS: Very few significant sex
      differences were found in the developmental history and in current levels of
      eating disorder features, as well as psychosocial factors. Women reported
      significantly earlier age at onset of overweight and dieting and greater
      frequency of dieting. Men reported more frequent strenuous exercise. Men were
      more likely than women to meet criteria for metabolic syndrome; men were more
      likely to show clinically elevated levels of triglycerides, blood pressure, and
      fasting glucose levels. CONCLUSION: Despite few sex differences in behavioral and
      psychosocial factors, metabolic problems associated with obesity were more common
      among treatment-seeking obese men with BED than women. The findings highlight the
      importance of including men in clinical studies of BED and active screening of
      BED in obese men at primary care settings.

PMID- 23969143
TI  - Effectiveness of collaborative care for depression in Italy. A randomized
      controlled trial.
AB  - TRIAL DESIGN: This was a multicenter cluster-randomized controlled trial.
      PARTICIPANTS: A total of 227 patients >=18 years old with a new onset of
      depressive symptoms who screened positive on the first two items of the Patient
      Health Questionnaire-9 (PHQ-9) were recruited by primary care physicians (PCPs)
      of eight health districts of three Italian regions from September 2009 to June
      2011. INTERVENTION: PCPs of the intervention group received a specific
      collaborative care program including 2 days of intensive training, implementation
      of a stepped care protocol, depression management toolkit and scheduled meetings
      with a dedicated consultant psychiatrist. OBJECTIVE: The objective was to
      determine whether a collaborative care program for depression management in
      primary care leads to higher remission rate than usual PCP care. OUTCOMES:
      Outcome was clinical remission as expressed on PHQ-9 <5 at 3 months.
      RANDOMIZATION: An independent researcher used computer-generated randomization to
      assign involved primary care groups to the two alternative arms. BLINDING: PCPs
      and research personnel were not blinded. RESULTS: The 223 PCPs enrolled recruited
      227 patients (128 in collaborative care arm, 99 in the usual care arm). At 3
      months (n=210), the proportion of patients who achieved remission was higher,
      though the difference was not statistically significant, in the collaborative
      care group. The effect size was of 0.11. When considering only patients with
      minor/major depression, collaborative care appeared to be more effective than
      usual care (P=.015). CONCLUSIONS: The present intervention for managing
      depression in primary care, designed to be applicable to the Italian context,
      appears to be effective and feasible.

PMID- 23969145
TI  - Interrelationship of psychological variables.

PMID- 23969144
TI  - Patient's views on depression care in obstetric settings: how do they compare to
      the views of perinatal health care professionals?
AB  - OBJECTIVES: The objectives were to examine patients' perspectives on patient-,
      provider- and systems-level barriers and facilitators to addressing perinatal
      depression in outpatient obstetric settings. We also compare the views of
      patients and perinatal health care professionals. METHOD: Four 90-min focus
      groups were conducted with women 3-36 months after delivery (n=27) who
      experienced symptoms of perinatal depression, anxiety or emotional distress.
      Focus groups were transcribed, and resulting data were analyzed using a grounded
      theory approach. RESULTS: Barriers to addressing perinatal depression included
      fear of stigma and loss of parental rights, negative experiences with perinatal
      health care providers and lack of depression management knowledge/skills among
      professionals. Facilitators included psychoeducation, peer support and training
      for professionals. CONCLUSIONS: Patients perceive many multilevel barriers to
      treatment that are similar to those found in our previous similar study of
      perinatal health care professionals' perspectives. However, patients and
      professionals do differ in their perceptions of one another. Interventions would
      need to close these gaps and include an empathic screening and referral process
      that facilitates discussion of mental health concerns. Interventions should
      leverage strategies identified by both patients and professionals, including
      empowering both via education, resources and access to varied mental health care
      options.

PMID- 23969146
TI  - Home electroacupuncture for persistent postsurgical pain: a patient's report.
AB  - A 30-year-woman presented with iatrogenic myofascial facial pain of 12 months'
      duration after surgical treatment for bilateral temporomandibular joint
      dysfunction. Limited response to manual acupuncture was followed by a trial of
      electroacupuncture. Response to electroacupuncture was limited in duration and
      one option was to teach her partner to perform electroacupuncture at home. The
      patient and partner, trained in beauty therapy, embraced this idea and it proved
      equally effective as therapist-provided acupuncture. We describe this case report
      from the perspective of the patient, caregiver or acupuncture partner and
      therapist. Home electroacupuncture seems to be safe, acceptable and practicable
      as a maintenance treatment for patients with persistent postsurgical pain of
      myofascial origin. 

PMID- 23969147
TI  - Partial craniofacial duplication: a review of the literature and case report.
AB  - Diprosopus (Greek; di-, "two" + prosopon, "face"), or craniofacial duplication,
      is a rare craniofacial anomaly referring to the complete duplication of facial
      structures. Partial craniofacial duplication describes a broad spectrum of
      congenital anomalies, including duplications of the oral cavity. This paper
      describes a 15 month-old female with a duplicated oral cavity, mandible, and
      maxilla. A Tessier type 7 cleft, midline meningocele, and duplicated hypophysis
      were also present. The preoperative evaluation, surgical approach, postoperative
      results, and a review of the literature are presented. The surgical approach was
      designed to preserve facial nerve innervation to the reconstructed cheek and
      mouth. The duplicated mandible and maxilla were excised and the remaining left
      maxilla was bone grafted. Soft tissue repair included closure of the Tessier type
      VII cleft. Craniofacial duplication remains a rare entity that is more common in
      females. The pathophysiology remains incompletely characterized, but is
      postulated to be due to duplication of the notochord, as well as duplication of
      mandibular growth centres. While diprosopus is a severe deformity often
      associated with anencephaly, patients with partial duplication typically benefit
      from surgical treatment. Managing craniofacial duplication requires a detailed
      preoperative evaluation as well as a comprehensive, staged treatment plan. Long
      term follow up is needed appropriately to address ongoing craniofacial deformity.

PMID- 23969148
TI  - Oral antidiabetic therapy in a large Italian sample: drug supply and compliance
      for different therapeutic regimens.
AB  - OBJECTIVES: To define the main features of patients treated with oral
      antidiabetics, evaluating monotherapy (MT), loose-dose combination therapy (LDCT)
      and fixed-dose combination therapy (FDCT); to describe medication adherence to
      the different therapies; and to evaluate the differences in compliance with the
      prescribed therapy regimen among prevalent and incident patient cohorts. STUDY
      DESIGN: This study was a retrospective cohort analysis based on the ARNO
      database, a national record that tracks reimbursable prescription claims
      submitted from selected pharmacies to the Italian national health system. In
      total, 169,375 subjects, from an overall population of 4,040,624 were included in
      this study. The patients represented 12 different local health units. Each
      patient had at least one oral antidiabetic prescription claim (A10B ATC code).
      METHODS: Patients were divided into four groups according to their treatment
      regimen during the recruitment period (1 January 2008-31 December 2008): MT,
      FDCT, LDCT and switching therapy. A timespan of 5 years was considered, from 4
      years before to 1 year after the index date (i.e. date of the prescription
      selected in the recruitment period). A medication possession ratio (MPR) with a
      cut-off value of 80% was used to measure medication adherence. Descriptive
      statistics and multiple logistic regression were used to define the objectives,
      while P < 0.05 was considered to indicate significance. RESULTS: The median age
      of patients (n = 169,375, prevalence 4.2%) was 70 years [interquartile range
      (IQR) 17], and 49.1% were females. Considering the entire sample, the median MPRs
      for the treatment regimens were: MT, 0.73 (IQR 0.53; 43.9% compliant); FDCT, 1
      (IQR 0.29, 68,5% compliant); and LDCT, 0.89 (IQR 0.33, 60.3% compliant). FDCT and
      LDCT were significantly correlated with MPR. Compliance was 48.9% in the
      prevalent patient cohort (i.e. patients prescribed oral antidiabetic therapy in
      both prerecruitment and recruitment periods); median MPRs for the treatment
      regimens were: MT, 0.73 (IQR 0.52); FDCT, 1 (IQR 0.28); and LDCT, 0.90 (IQR
      0.32). Compliance was 43.0% in the incident patient cohort (i.e. patients who
      were first prescribed oral antidiabetic therapy in the recruitment period);
      median MPRs for the treatment regimens were: MT, 0.70 (IQR, 0.58); FDCT, 1 (IQR
      0.34); and LDCT, 0.64 (IQR 0.39). CONCLUSIONS: Compliance was better for FDCT
      than the other therapeutic regimens in the study population. The same trend was
      observed in both the prevalent and incident patient cohorts. As type 2 diabetes
      is a chronic lifelong pathology, and multiple agents are often required to
      achieve glycaemic control, the preference for FDCT in the population, when
      clinically applicable, could be an effective strategy for functional
      administration of clinical outcome and sources. Evaluation of specific population
      fractions (age, sex, compliance, etc.) and specific agents or drug combinations
      could also be relevant in order to reach the healthcare objectives.

PMID- 23969149
TI  - Lipoma arborescens: comparison of typical and atypical disease presentations.
AB  - AIM: To determine whether the aetiology differed between typical cases of lipoma
      arborescens with unilateral knee involvement and atypical cases involving joints
      other than the knee, polyarticular disease, and disease outside of the knee
      joint. MATERIALS AND METHODS: Cases of lipoma arborescens involving the knee
      joint were evaluated for the distribution of the disease and severity of
      degenerative arthritis. Joints other than the knee were evaluated for the
      presence and severity of degenerative arthritis, and the distribution was
      classified as either intra-articular, extra-articular, or both. Clinical history
      was reviewed for patient age at presentation, a history of inflammatory
      arthritis, diabetes mellitus, and known steroid use. Fisher's exact test was used
      to determine whether there was a statistically significant difference between
      typical and atypical presentations of the disease. RESULTS: Lipoma arborescens
      was identified in 45 joints in 39 patients. Twenty-eight patients were classified
      as "typical" and 11 patients had "atypical" disease. There was no significant
      difference in age at presentation, presence of degenerative arthritis, or known
      inflammatory arthritis when comparing typical and atypical presentations of the
      disease. CONCLUSION: Twenty-eight percent of patients in the present study had
      atypical presentation of lipoma arborescens with multifocal lipoma arborescens or
      disease in joints other than the knee. There was no significant difference in age
      at presentation, presence of degenerative arthritis, or known inflammatory
      arthritis when comparing typical and atypical presentations of the disease. Of
      the 39 patients, only three had no evidence of degenerative arthritis, which
      suggests that many cases of lipoma arborescens are secondary to chronic reactive
      change in association with degenerative arthritis.

PMID- 23969150
TI  - Ultrasonographic elastography of thyroid nodules: is adding strain ratio to
      colour mapping better?
AB  - AIM: To determine the diagnostic performance of colour mapping and strain ratio
      for characterizing malignant thyroid nodules on ultrasonographic (US)
      elastography. MATERIALS AND METHODS: The study was approved by the institutional
      review board and written informed consent was obtained. One hundred and thirty
      one patients with 142 thyroid nodules >0.5 cm were prospectively enrolled between
      July 2010 and January 2011. Seven radiologists performed US elastography (iU22
      Vision 2010; Philips, Seattle, WA, USA) using colour mapping and strain ratio for
      thyroid nodules blinded to the cytopathological results. Diagnostic performances
      of colour mapping alone, strain ratio alone, colour mapping and strain ratio, and
      colour mapping or strain ratio were compared using receiver operating
      characteristic (ROC) curve analysis. RESULTS: Of the 142 nodules, 69 (48.6%) were
      benign and 73 (51.4%) were malignant. Colour mapping of elastography showed a
      more frequent blue colour in malignant nodules than in benign nodules (65.8%
      versus 24.6%, p < 0.0001). A higher ratio than 1.21 as the best cut-off value was
      found in 65.8% of malignant nodules and 46.4% of benign nodules (p = 0.030). Area
      under the ROC curve (AUC) of colour mapping alone was significantly greater than
      that of colour mapping or strain ratio (AUC = 0.706 versus AUC = 0.63, p =
      0.0195) and similar to that of colour mapping and strain ratio (AUC = 0.673, p =
      0.1364). CONCLUSION: US elastography is helpful to predict malignant thyroid
      nodules. However, adding strain ratio to colour mapping does not improve
      performance compared to colour mapping alone.

PMID- 23969151
TI  - Assessment of extent of breast cancer: comparison between digital breast
      tomosynthesis and full-field digital mammography.
AB  - AIM: To compare the accuracy of digital breast tomosynthesis (DBT) and full-field
      digital mammography (FFDM) in preoperative assessment of local extent of breast
      cancer. MATERIALS AND METHODS: Lesion sizes of breast cancers on DBT and FFDM
      images were independently evaluated by breast radiologists. Each lesion was
      flagged as either mis-sized or not depending on whether the assessment of size at
      imaging was within 1 cm of the lesion size at surgery. Additional analyses were
      made by mammographic parenchymal density and by lesion size, using 2 cm as the
      boundary to separate the two subgroups. Statistical comparisons were performed
      using a repeated measures linear model on the percent mis-sized. P-values < 0.05
      were considered statistically significant. RESULTS: The dataset included 173
      malignant breast lesions (mean size 23.8 mm, 43% of lesions were <=2 cm in size)
      in 169 patients, two-thirds of which had heterogeneously or extremely dense
      breasts. Overall, the percentage of lesions mis-sized at DBT was significantly
      lower than at FFDM (19% versus 29%, p = 0.003). There was significantly less mis
      sizing at DBT in both heterogeneously dense breasts (11.1% difference between DBT
      and FFDM, p = 0.016) and extremely dense breasts (15.8% difference, p = 0.024).
      DBT also had significantly less mis-sizing than FFDM in the subgroup of lesions
      that were <=2 cm in size (14.7% difference, p = 0.005). CONCLUSION: DBT was
      significantly superior to FFDM for the evaluation of lesion size overall, and
      specifically for small lesions and for lesions in dense breasts. The superiority
      of DBT versus FFDM increased with parenchymal density.

PMID- 23969152
TI  - Feasibility of MR imaging in evaluating breast cancer lymphangiogenesis using
      Polyethylene glycol-GoldMag nanoparticles.
AB  - AIM: To investigate the feasibility of evaluating tumour lymphangiogenesis using
      magnetic resonance imaging (MRI) in vivo. MATERIALS AND METHODS: Water-soluble
      polyethylene glycol (PEG)-GoldMag nanoparticles were obtained by combining
      GoldMag with PEG. The PEG-GoldMag nanoparticles were bound to anti-podoplanin
      antibody (PodAb) to construct PEG-GoldMag-pod molecular probes targeting
      lymphatic endothelial cells (LECs). The characteristics of the PEG-GoldMag-pod
      nanoparticles were tested. Using these nanoparticles, tumour lymphangiogenesis
      was evaluated using MRI in vitro and in vivo. RESULTS: The average size of PEG
      GoldMag nanoparticles was about 66.8 nm, and the nanoparticles were stably
      dispersed in the liquid phase for at least 15 days. After incubation for 24 h at
      different iron concentrations ranging from 5-45 MUg/ml, the LECs were labelled
      with PEG-GoldMag-pod nanoparticles, in particular the breast cancer LECs. Dose
      dependence was observed in the labelling efficiencies and MRI images of the
      labelled cells. In vitro, the labelling efficiencies and MRI images showed that
      the nanoparticles could detect podoplanin expression in LECs. In induced rat
      models of breast cancer, PEG-GoldMag-pod nanoparticles combined with lymphatic
      vessels were significantly detectable at MRI 60 min after nanoparticle
      administration, the signal intensity was negatively correlated with the lymphatic
      vessel density of breast cancer (r = -0.864, P = 0.000). CONCLUSIONS: The present
      study proves the feasibility of evaluating tumour lymphangiogenesis with MRI in
      vivo.

PMID- 23969153
TI  - Potential role of advanced MRI techniques for the peritumoural region in
      differentiating glioblastoma multiforme and solitary metastatic lesions.
AB  - Differentiation between solitary metastatic lesions and glioblastomas, two of the
      most common malignant brain neoplasms, is often a diagnostic challenge. The
      purpose of this review is to emphasize the potential roles of advanced magnetic
      resonance imaging (MRI) techniques, including diffusion-based techniques, such as
      diffusion-weighted imaging (DWI), exponential DWI, and diffusion tensor imaging,
      MR perfusion, and MR spectroscopy, as well as conventional MRI, in making a
      distinction between glioblastomas and solitary metastases in peritumoural
      regions. Integration of advanced MRI features with conventional MRI, may provide
      valuable information for differentiating glioblastoma from solitary metastatic
      lesions. 

PMID- 23969154
TI  - Discrepancies in discrepancy meetings: results of the UK national discrepancy
      meeting survey.
AB  - AIM: To present the findings of the UK national discrepancy meeting survey of
      radiology departments across England, Wales, Scotland, and Northern Ireland
      regarding the way in which discrepancy meetings are currently conducted. This is
      in the setting of impending changes required for revalidation. MATERIALS AND
      METHODS: One hundred and fourteen (114) out of 195 (55%) of departments surveyed
      replied to an anonymous survey of 10 questions requesting information regarding
      the proportion of departments adopting a regular meeting, the consultant hours
      spent at the meeting, the system used and people involved in the identification
      of discrepancies, whether a grading system was used, and whether discrepancies
      were recorded on consultants appraisals. RESULTS: Ninety-seven percent of
      responders reported that their department has a regular discrepancy meeting.
      Among the responders, the average consultant attendance was 68%. Seven percent of
      departments did not record attendance. In departments that conduct discrepancy
      meetings, the number of cases discussed per month averaged 10. The average time
      spent per case was 6 min. Seventeen percent of departments ensure discrepancies
      form part of a consultant's appraisal. Twenty-seven percent reported not having a
      grading system, whereas those that do, use varying systems. Ninety-four percent
      reported that the majority of errors were identified by radiologists. Ten percent
      of departments undertake a systematic consultant review of random reported cases.
      CONCLUSION: Discrepancy meetings provide a crucial role in clinical governance by
      facilitating an improvement in the quality of service provided by the radiology
      department. After more than a decade since the introduction of discrepancy
      meetings in the UK, there remains a great variety in implementation across the
      country, and important considerations, such as the need for grading and recording
      discrepancies in consultant appraisals. Reflection on discrepancies and also
      attendance at discrepancy meetings is required for impending revalidation.

PMID- 23969155
TI  - Oximetry-derived perfusion index as an early indicator of CT-guided thoracic
      sympathetic blockade in palmar hyperhidrosis.
AB  - AIM: To test the hypothesis that the oximetry-derived perfusion index (PI)
      recorded in the index finger may provide earlier objective evidence for correct
      positioning of the needle tip during computed tomography (CT)-guided thoracic
      sympathetic blockade than skin temperature in palmar hyperhidrosis. MATERIALS AND
      METHODS: Forty-four CT-guided thoracic sympathetic blockades were prospectively
      performed in both hands of 22 patients. Prior to chemical blockade, PI and skin
      temperature were recorded at 1 min intervals until 20 min after lidocaine
      injection. Repeated measures analysis of variance was used to assess the potency
      of PI and skin temperature over time. Using a 100% increase in the PI as the
      threshold and symptom relief within 20 min as the reference standard, the
      sensitivity and specificity for predicting a successful injection were
      calculated. RESULTS: Thirty-seven (84%) sympathetic blockade procedures were
      clinically successful. For successful cases, the PI increased as early as 1 min
      after the blockade of the sympathetic chain (p < 0.05), whereas the skin
      temperature showed statistical significance 1 min later (p < 0.05). The PI can be
      used to indicate a successful CT-guided sympathetic blockade with 97% sensitivity
      and 100% specificity 3 min after lidocaine injection. CONCLUSION: The PI, a more
      marked and sensitive indicator than changes in skin temperature, can be used to
      indicate a successful CT-guided sympathetic blockade with satisfying sensitivity
      and specificity, 3 min after lidocaine injection in palmar hyperhidrosis.

PMID- 23969156
TI  - Construction and immunological evaluation of truncated hepatitis B core particles
      carrying HBsAg amino acids 119-152 in the major immunodominant region (MIR).
AB  - Hepatitis B capsid protein expressed in Escherichia coli can reassemble into
      icosahedral particles, which could strongly enhance the immunogenicity of foreign
      epitopes, especially those inserted into its major immunodominant region. Herein,
      we inserted the entire 'alpha' antigenic determinant amino acids (aa) 119-152 of
      HBsAg into the truncated HBc (aa 1-144), between Asp(78) and Pro(79). Prokaryotic
      expression showed that the mosaic HBc was mainly in the form of inclusion bodies.
      After denaturation with urea, it was dialyzed progressively for protein
      renaturation. We observed that before and after renaturation, mosaic HBc was
      antigenic as determined by HBsAg ELISA and a lot of viruslike particles were
      observed after renaturation. Thus, we further purified the mosaic viruslike
      particles by (NH4)2SO4 precipitation, DEAE chromatography, and Sepharose 4FF
      chromatography. Negative staining electron microscopy demonstrated the morphology
      of the viruslike particles. Immunization of Balb/c mice with mosaic particles
      induced the production of anti-HBs antibody and Th1 cell immune response
      supported by ELISPOT and CD4/CD8 proportions assay. In conclusion, we constructed
      mosaic hepatitis core particles displaying the entire 'alpha' antigenic
      determinant on the surface and laid a foundation for researching therapeutic
      hepatits B vaccines.

PMID- 23969157
TI  - Functional analysis of the distal region of the third intracellular loop of
      PROKR2.
AB  - Mutations in the G-protein-coupled receptor PROKR2 have been identified in
      patients with idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann
      syndrome (KS) manifesting with delayed puberty and infertility. Recently, the
      homozygous mutation V274D was identified in a man displaying KS with an apparent
      reversal of hypogonadism. The affected amino acid, valine 274, is located at the
      junction region of the third intracellular loop (IL3) and the sixth transmembrane
      domain (TM6). In this study, we first studied the effect of V274D and related
      mutations (V274A, V274T, and V274R) on the signaling activity and cell surface
      expression of PROKR2. Our data indicate that a charged amino acid substitution at
      residue 274 of PROKR2 results in low cell surface expression and loss-of
      function. Furthermore, we studied the effects of two clusters of basic amino
      acids located at the proximal region of Val274 on the cell surface expression and
      function of PROKR2. The deletion of RRK (270-272) resulted in undetectable cell
      surface expression, whereas RKR (264-266)-deleted PROKR2 was expressed normally
      on the cell surface but showed loss-of-function due to a deficiency in G-protein
      coupling. Our data indicate that the distal region of the IL3 of PROKR2 may
      differentially influence receptor trafficking and G-protein coupling.

PMID- 23969159
TI  - Central nervous system pathology in MFP2 deficiency: insights from general and
      conditional knockout mouse models.
AB  - Multifunctional protein-2 (MFP2), also known as D-bifunctional protein, is a
      central enzyme of the peroxisomal beta-oxidation pathway. Defects in this enzyme
      are associated with a spectrum of neurological disorders encompassing
      developmental and degenerative pathologies. In order to investigate the cellular
      and molecular mechanisms of these neuropathologies, mouse models with general and
      cell type selective loss of MFP2 were generated. In this review the distinct
      anomalies in the CNS of adult Mfp2 knockout mice are discussed, in particular the
      cerebellar degeneration and neuroinflammation. The potential underlying
      mechanisms are considered with regard to the cellular origin and biochemical
      causes. Finally, the similarities and differences between the CNS phenotypes of
      mice lacking MFP2 and mice with peroxisome biogenesis disorders are assessed. 

PMID- 23969160
TI  - Controlled polymorphic transformation of continuously crystallized solid lipid
      nanoparticles in a microstructured device: a feasibility study.
AB  - The contribution describes the transfer from a batch to a micro-continuous
      process for the production of stable solid lipid nanoparticles as drug carrier
      systems. Solid lipid nanoparticles are commonly prepared batch-wise often
      resulting in poorly defined product qualities with regard to the polymorphic
      state of their lipid matrix. In order to obtain solid lipid nanoparticle
      dispersions that meet the requirements for an acceptable pharmaceutical product,
      the manufacture of reproducible product qualities preferably containing the
      stable crystal form of the respective matrix lipid is necessary. These requests
      are addressed by the continuous preparation process of solid lipid nanoparticles.
      A four step feasibility study for the standardized evaluation whether or not a
      colloidal lipid dispersion is suitable for continuous crystallization of the
      particles resulting in stable crystal forms is presented. The process is based on
      the continuous crystallization and subsequent thermal treatment of differently
      stabilized, tripalmitin-based nanoparticle formulations in microstructured
      devices. The successful production of the stable crystal form by means of a
      continuous process chain is shown for a dispersion stabilized with a blend of
      hydrogenated soybean lecithin and sodium glycocholate. 

PMID- 23969158
TI  - The adipokine/ceramide axis: key aspects of insulin sensitization.
AB  - Until recently, sphingolipid physiology was primarily the domain of oncologists
      and immunologists. However, mounting evidence implicates ceramides and their
      derivatives in various aspects of metabolism via directly impacting the insulin
      receptor as well as modulating cell survival and proliferation. More recent
      observations suggest a strong link between a number of adipokines and ceramide
      catabolism. Here, we aim to briefly review the available data on the established
      metabolic effects of sphingolipids in various cell types and will discuss how
      adipokines exert a critical influence on the steady state levels of these lipid
      mediators. 

PMID- 23969161
TI  - Radial anatomic variation of ultrasonic velocity in human cortical bone.
AB  - Quantitative ultrasound techniques can be used to retrieve cortical bone quality.
      The aim of this study was to investigate the anatomic variations in speed of
      sound (SOS) in the radial direction of cortical bone tissue. SOS measurements
      were realized in 17 human cortical bone samples with a 3.5-MHz transverse
      transmission device. The radial dependence of SOS was investigated in a direction
      perpendicular to the periosteum. For each sample, bone porosity was measured
      using an X-ray micro-computed tomography device. The mean SOS was 3586 +/- 255
      m/s. For 16 of 17 specimens, similar radial variations in SOS were observed. In
      the periosteal region, SOS first decreased in the direction of the endosteum and
      reached a minimum value approximately in the middle of the cortical bone. SOS
      then increased, moving to the endosteal region. A significant negative
      correlation was obtained between SOS and porosity (R = -0.54, p = 0.02). 

PMID- 23969162
TI  - Motion analysis of right ventricular dysfunction under mild or moderate pressure
      overload caused by acute pulmonary embolism.
AB  - Acute pulmonary embolism (APE) is the third most common cause of death in the
      United States. Appearing as a sudden blockage in a major pulmonary artery, APE
      may cause mild, moderate or severe right ventricular (RV) overload. Although
      severe RV overload produces diagnostically obvious RV mechanical failure, little
      progress has been made in gaining a clinical and biophysical understanding of
      moderate and mild acute RV overload and its impact on RV functionality. In the
      research described here, we conducted a pilot study in pigs using
      echocardiography and observed the following abnormalities in RV functionality
      under acute mild or moderate RV overload: (i) occurrence of paradoxical septal
      motion with "waving" dynamics; (ii) decrease in local curvature of the septum (p
      < 0.01); (iii) lower positive correlation between movement of the RV free wall
      and movement of the septum (p < 0.05); (iv) slower rate of RV fractional area
      change (p < 0.05); and (v) decrease in movement stability, particularly in the
      middle of the septum (p < 0.05). 

PMID- 23969163
TI  - Use of optical flow to estimate continuous changes in muscle thickness from
      ultrasound image sequences.
AB  - Muscle thickness is one of the most widely used parameters for quantifying muscle
      function. Ultrasonography is frequently used to estimate changes in muscle
      thickness in both static and dynamic contractions. Conventionally, most such
      measurements are conducted by manual analysis of ultrasound images. This manual
      approach is time consuming, subjective, susceptible to error and not suitable for
      measuring dynamic change. In this study, we developed an automated tracking
      method based on an optical flow algorithm using an affine motion model. The goal
      of the study was to evaluate the performance of the proposed method by comparing
      it with the manual approach and by determining its repeatability. Real-time B
      mode ultrasound was used to examine the rectus femoris during voluntary
      contraction. The coefficient of multiple correlation (CMC) was used to quantify
      the level of agreement between the two methods and the repeatability of the
      proposed method. The two methods were also compared by linear regression and
      Bland-Altman analysis. The findings indicated that the results obtained using the
      proposed method were in good agreement with those obtained using the manual
      approach (CMC = 0.97 +/- 0.02, difference = -0.06 +/- 0.22 mm) and were highly
      repeatable (CMC = 0.91 +/- 0.07). In conclusion, the automated method proposed
      here provides an accurate, highly repeatable and efficient approach to the
      estimation of muscle thickness during muscle contraction. 

PMID- 23969164
TI  - Comparison of two methods for calculating the mean vascularization index of
      ovarian stroma on the basis of spatio-temporal image correlation high-definition
      flow technology.
AB  - The aim of our study was to determine the agreement between two different methods
      for calculating the mean vascularization index (VI) of ovarian stroma using
      spatio-temporal image correlation-high definition flow (STIC-HDF) technology.
      Stored 4-D STIC-HDF volume data for ovaries of 34 premenopausal women were
      assessed retrospectively. We calculated the mean VI from the VI values derived
      for each 3-D volume within the STIC sequence. Then, the examiner subjectively
      selected the two volumes with the highest and lowest color signals, respectively.
      We averaged these two values. Agreement between VI measurements was estimated by
      calculating intra-class correlation coefficients. The intra-class correlation
      coefficient for the VI was 0.999 (95% confidence interval: 0.999-1.000). The mean
      time needed to calculate the mean VI using the entire 4-D STIC sequence was
      significantly longer than the mean time needed to calculate the average value
      from the volumes with the highest and lowest color signals determined by the
      operator (p < 0001). We conclude that there is significant agreement between the
      two methods. Calculating the average VI from the highest and lowest values is
      less time consuming than calculating the mean VI from the complete STIC sequence.

PMID- 23969165
TI  - Value of contrast-enhanced ultrasound using perflubutane microbubbles for
      diagnosing liver fibrosis and cirrhosis in rats.
AB  - We determined the ability of contrast-enhanced ultrasound (CEUS) using
      perflubutane microbubbles to diagnose liver fibrosis and cirrhosis in rats using
      histology as the reference standard. Fibrosis was induced by oral administration
      of carbon tetrachloride to 32 Wistar rats. Features with baseline ultrasound (US)
      and enhancement level of liver and spleen with CEUS were obtained. In the post
      vascular phase of CEUS, images of normal livers (n = 5) were significantly
      brighter than images of fibrotic (n = 6) and cirrhotic livers (n = 13) by
      quantitative analysis (all p < 0.05). The contrast between livers and spleens in
      rats with cirrhosis was quantitatively greater than that in normal rats and rats
      with fibrosis (all p < 0.05). Compared with US, CEUS improved sensitivity from
      63% to 84% and accuracy from 71% to 88%. Specificity was 100% for both. The
      increased value of CEUS in diagnosing liver fibrosis and cirrhosis in rats
      supports its evaluation in clinical trials. 

PMID- 23969166
TI  - Contrast-enhanced ultrasound evaluation of splenic embolization in patients with
      definite left-sided infective endocarditis.
AB  - The purpose of the study described here was to prospectively evaluate the
      significance of embolization of the spleen in patients with definite left-sided
      infective endocarditis (IE) using contrast-enhanced ultrasound (CEUS). From March
      through October 2012, 6 consecutive patients (4 females and 2 males, aged 27 to
      83 years) with definite left-sided IE according to the revised Duke criteria were
      enrolled. All patients gave informed written consent, and the study was performed
      in conformity with the ethical guidelines of the Declaration of Helsinki. All
      patients underwent CEUS of the spleen within 1 week of the definite diagnosis of
      IE. A blood pool second-generation contrast agent and an ultrasound machine with
      contrast harmonic imaging technology were used for CEUS. Fifteen consecutive
      patients (7 females and 8 males, aged 39 to 88 years) who underwent CEUS from
      October through November 2012 for the study of focal liver lesions constituted
      the control group. The number of patients did not permit statistical analysis.
      Splenic CEUS revealed infarctions in 5 patients and an infarcted area in the only
      patient with negative echocardiography. All splenic CEUS procedures in the
      control group were negative. In this study, CEUS of the spleen, a repeatable and
      low-cost imaging technique, easily allowed bedside detection of asymptomatic and
      even tiny infarctions, and revealed a high rate of embolization in patients with
      definite left-sided IE. Indeed, splenic CEUS, if applied to the workup of
      patients with suspect IE, has the potential to accelerate or upgrade the
      diagnosis itself. 

PMID- 23969167
TI  - Ultrasound targeted microbubble destruction promotes angiogenesis and heart
      function by inducing myocardial microenvironment change.
AB  - The myocardial microenvironment plays a decisive role in the survival, migration
      and differentiation of stem cells. We studied myocardial micro-environmental
      changes induced by ultrasound-targeted microbubble destruction (UTMD) and their
      influence on the transplantation of mesenchymal stem cells (MSCs). Various
      intensities of ultrasound were applied to the anterior chest in canines with
      myocardial infarction after intravenous injection of microbubbles. The expression
      of cytokines and adhesion molecules in the infarcted area of the myocardium was
      detected after three sessions of UTMD in 1 wk. Real-time quantitative reverse
      transcription polymerase chain reaction (RTQ-PCR) showed that the expression of
      vascular cell adhesion molecule-1 (VCAM-1), stromal cell-derived factor-1 (SDF-1)
      and vascular endothelial growth factor (VEGF) in the 1.5 W/cm(2) and 1 W/cm(2)
      groups was markedly increased compared with the 0.5 W/cm(2) or the control groups
      (3.8- to 4.7-fold, p < 0.01), and the expression of interleukin-1beta (IL-1beta)
      in the 1.5 W/cm(2) group was increased twofold over the 1.0 W/cm(2) group,
      whereas the 0.5 W/cm(2) group experienced no significant changes. UTMD at 1.0
      W/cm(2) was performed as previously described before mesenchymal stem cell (MSC)
      transplantation. Myocardial perfusion, angiogenesis and heart function were
      investigated before and 1 month after MSC transplantation. Coronary angiography
      and 99mTc-tetrofosmin scintigraphy revealed that myocardial perfusion was
      markedly improved after UTMD + MSCs treatment (p < 0.05). At echocardiographic
      analysis, heart function and the wall motion score index were significantly
      improved by UTMD + MSCs treatment compared with MSCs or UTMD alone and the
      control. In a canine model of myocardial infarction, therapeutic effects were
      markedly enhanced by MSC transplantation after the myocardial micro-environmental
      changes induced by UTMD; therefore, this novel method may be useful as an
      efficient approach for cellular therapy. 

PMID- 23969168
TI  - Carnitine palmitoyltransferase 2 gene polymorphism is a genetic risk factor for
      sudden unexpected death in infancy.
AB  - RATIONALE: Carnitine palmitoyltransferase (CPT) II is one of a pivotal enzyme in
      mitochondrial fatty acid oxidation, which is essential for energy production
      during simultaneous glucose sparing and a requirement for major energy supply,
      such as prolonged fasting or exercise. When infants require more energy than
      provided by the glycolytic system, they rely on the mitochondrial fatty acid
      oxidation pathway. Mutations of the CPT2 gene have been reported to cause sudden
      unexpected death in infancy (SUDI). A thermolabile phenotype of a CPT2
      polymorphism (F352C) has been recently reported to reduce CPT II enzyme activity.
      The F352C variant results in energy crisis at high temperature and is suspected
      as a risk factor for acute encephalopathy. However, a relationship between CPT2
      gene polymorphism and SUDI has not been described. METHODS: Single nucleotide
      polymorphisms of the CPT2 gene were investigated among 54 SUDI cases and 200
      healthy volunteers. RESULTS: The frequency of the C allele was significantly
      higher in the SUDI group than in the control group [25.0% vs 16.0%, odds ratio
      (OR)=1.75, 95% confidence interval (CI)=1.05-2.92, p=0.030). The frequency of the
      F352C homozygote was significantly higher in the SUDI group than in control group
      (11.1% vs 3.5%, OR=3.45, 95% CI=1.11-10.73, p=0.036). CONCLUSION: The F352C CPT2
      variant might be a genetic risk factor for SUDI.

PMID- 23969169
TI  - Registration of 3D fetal neurosonography and MRI.
AB  - We propose a method for registration of 3D fetal brain ultrasound with a
      reconstructed magnetic resonance fetal brain volume. This method, for the first
      time, allows the alignment of models of the fetal brain built from magnetic
      resonance images with 3D fetal brain ultrasound, opening possibilities to develop
      new, prior information based image analysis methods for 3D fetal neurosonography.
      The reconstructed magnetic resonance volume is first segmented using a
      probabilistic atlas and a pseudo ultrasound image volume is simulated from the
      segmentation. This pseudo ultrasound image is then affinely aligned with clinical
      ultrasound fetal brain volumes using a robust block-matching approach that can
      deal with intensity artefacts and missing features in the ultrasound images. A
      qualitative and quantitative evaluation demonstrates good performance of the
      method for our application, in comparison with other tested approaches. The
      intensity average of 27 ultrasound images co-aligned with the pseudo ultrasound
      template shows good correlation with anatomy of the fetal brain as seen in the
      reconstructed magnetic resonance image. 

PMID- 23969174
TI  - Is it really a thyroid nodule?

PMID- 23969175
TI  - An unusual cause of gastrointestinal bleeding: there is more than meets the eye.

PMID- 23969176
TI  - Don't blame it on the scar tissue.

PMID- 23969177
TI  - Magnetic resonance spectroscopy in mild cognitive impairment: systematic review
      and meta-analysis.
AB  - Research using proton magnetic resonance spectroscopy (MRS) can potentially
      elucidate metabolite changes representing early degeneration in Mild Cognitive
      Impairment (MCI), an early stage of dementia. We integrated the published
      literature using meta-analysis to identify patterns of metabolite changes in MCI.
      29 MRS studies (with a total of 607 MCI patients and 862 healthy controls) were
      classified according to brain regions. Hedges' g was used as effect size in a
      random effects model. N-Acetyl Aspartate (NAA) measures were consistently reduced
      in posterior cingulate (PC), hippocampus, and the paratrigonal white matter
      (PWM). Creatine (Cr) concentration was reduced in the hippocampus and PWM.
      Choline (Cho) concentration was reduced in the hippocampus while Cho/Cr ratio was
      raised in the PC. Myo-inositol (mI) concentration was raised in the PC and mI/Cr
      ratio was raised in the hippocampus. NAA/mI ratio was reduced in the PC. NAA may
      be the most reliable marker of brain dysfunction in MCI though mI, Cho, and Cr
      may also contribute towards this. 

PMID- 23969179
TI  - Complex and region-specific changes in astroglial markers in the aging brain.
AB  - Morphological aging of astrocytes was investigated in entorhinal cortex (EC),
      dentate gyrus (DG), and cornu ammonis 1 (CA1) regions of hippocampus of male
      SV129/C57BL6 mice of different age groups (3, 9, 18, and 24 months). Astroglial
      profiles were visualized by immunohistochemistry by using glial fibrillary acidic
      protein (GFAP), glutamine synthetase (GS), and s100beta staining; these profiles
      were imaged using confocal or light microscopy for subsequent morphometric
      analysis. GFAP-positive profiles in the DG and the CA1 of the hippocampus showed
      progressive age-dependent hypertrophy, as indicated by an increase in surface,
      volume, and somata volume at 24 months of age compared with 3-month-old mice. In
      contrast with the hippocampal regions, aging induced a decrease in GFAP-positive
      astroglial profiles in the EC: the surface, volume, and cell body volume of
      astroglial cells at 24 months of age were decreased significantly compared with
      the 3-month group. The GS-positive astrocytes displayed smaller cellular surface
      areas at 24 months compared with 3-month-old animals in both areas of
      hippocampus, whereas GS-positive profiles remained unchanged in the EC of old
      mice. The morphometry of s100beta-immunoreactive profiles revealed substantial
      increase in the EC, more moderate increase in the DG, and no changes in the CA1
      area. Based on the morphological analysis of 3 astroglial markers, we conclude
      that astrocytes undergo a complex age-dependent remodeling in a brain region
      specific manner. 

PMID- 23969178
TI  - Blood pressure decrease correlates with tau pathology and memory decline in
      hypertensive elderly.
AB  - In hypertension (HTN), cerebral blood flow regulation limits are changed, and the
      threshold for blood pressure (BP) at which perfusion is safely maintained is
      higher. This shift may increase the brain's vulnerability to lower BP in subjects
      with vascular disease. We investigated whether longitudinal reduction in mean
      arterial pressure (MAP) was related to changes in cerebrospinal fluid (CSF)
      biomarkers of Alzheimer's disease in a group of cognitively healthy elderly with
      and without HTN. The relationships among MAP, memory decline, and hippocampal
      atrophy were also examined. Seventy-seven subjects (age 63.4 +/- 9.4, range 44-86
      years; education 16.9 +/- 2.1, range 10-22 years; 60% women) were assessed twice,
      2 +/- 0.5 years apart. At both time points, all subjects underwent full medical
      and neuropsychological evaluations, lumbar punctures, and magnetic resonance
      imaging examinations. Twenty-five subjects had HTN. Hyper- and normotensive
      subjects did not differ in their CSF biomarkers, hippocampal volumes (HipVs), or
      memory scores at baseline. In the entire study group, the increase in tau
      phosphorylated at threonine 181 (p-tau(181)) was associated with a decline in
      verbal episodic memory (beta = -0.30, p = 0.01) and HipV reduction (beta = -0.27,
      p = 0.02). However, longitudinal decrease in MAP was related to memory decline
      (beta = 0.50, p = 0.01) and an increase in p-tau(181) (beta = -0.50, p = 0.01)
      only in subjects with HTN. Our findings suggest that the hypertensive group may
      be sensitive to BP reductions.

PMID- 23969181
TI  - Petrosal ganglion responses to acetylcholine and ATP are enhanced by chronic
      normobaric hypoxia in the rabbit.
AB  - In mammals, adaptation to chronic hypoxia requires the integrity of the arterial
      chemoreceptors, specially the carotid body (CB). Chronic hypoxia increases the
      sensibility of the CB by acting on the receptor cells, but there is limited
      information on the effects of chronic hypoxia on the sensory neurons that
      innervate the CB. Therefore, we studied the responses evoked by ACh and ATP, the
      main transmitters that generate the chemoafferent activity, on the petrosal
      ganglion (PG) of rabbits exposed to chronic normobaric hypoxia (CNH) during
      fourteen days. ATP and ACh increased the activity of PG neurons in a dose
      dependent manner, in a similar way than in rabbits not exposed to hypoxia
      (naive). However, the duration of the responses were significantly increased by
      CNH, with the mean maximal responses to ACh and ATP increased by a factor of two
      and four, respectively. Our results suggest that CNH increases duration of the
      responses by modifying the expression and/or content of ACh and ATP receptors. 

PMID- 23969180
TI  - SAMP8 mice have altered hippocampal gene expression in long term potentiation,
      phosphatidylinositol signaling, and endocytosis pathways.
AB  - The senescence-accelerated mouse (SAMP8) strain exhibits decreased learning and
      memory and increased amyloid beta (Abeta) peptide accumulation at 12 months. To
      detect differences in gene expression in SAMP8 mice, we used a control mouse that
      was a 50% cross between SAMP8 and CD-1 mice and which showed no memory deficits
      (50% SAMs). We then compared gene expression in the hippocampus of 4- and 12
      month-old SAMP8 and control mice using Affymetrix gene arrays. At 12 months, but
      not at 4 months, pathway analysis revealed significant differences in the long
      term potentiation (6 genes), phosphatidylinositol signaling (6 genes), and
      endocytosis (10 genes) pathways. The changes in long term potentiation included
      mitogen-activated protein kinase (MAPK) signaling (N-ras, cAMP responsive element
      binding protein [CREB], protein phosphatase inhibitor 1) and Ca-dependent
      signaling (inositol triphosphate [ITP] receptors 1 and 2 and phospholipase C).
      Changes in phosphatidylinositol signaling genes suggested altered signaling
      through phosphatidylinositol-3-kinase, and Western blotting revealed
      phosphorylation changes in serine/threonine protein kinase AKT and 70S6K. Changes
      in the endocytosis pathway involved genes related to clathrin-mediated
      endocytosis (dynamin and clathrin). Endocytosis is required for receptor
      recycling, is involved in Abeta metabolism, and is regulated by
      phosphatidylinositol signaling. In summary, these studies demonstrate altered
      gene expression in 3 SAMP8 hippocampal pathways associated with memory formation
      and consolidation. These pathways might provide new therapeutic targets in
      addition to targeting Abeta metabolism itself.

PMID- 23969182
TI  - Forensic medicine experts' opinion on medico-legal autopsies in hospital deaths:
      a questionnaire survey.
AB  - OBJECTIVE: Medico-legal autopsy is conducted routinely in some countries and
      selectively in others in hospital deaths. This study was conducted to evaluate
      the views of the forensic medicine experts regarding this matter. METHODS: A
      questionnaire pro forma was sent to sixty-five forensic medicine experts
      practicing in different medical institutions all around India. Designations and
      experiences of the participants were noted by requests in the same questionnaire.
      Their specific experience in conducting medico-legal autopsy in hospital deaths
      was also requested for. Responses were charted in frequency distribution tables
      and analyzed using SPSS, version 17.0. RESULTS: One-third of the participants
      felt that a medico-legal autopsy was necessary in all the hospital death cases as
      defined in the present study. Ten percent of the participants opined that a
      medico-legal autopsy was unnecessary in hospital deaths. The majority of the
      experts mentioned finding the cause of death, followed by finding the manner of
      death and collecting the evidentiary materials, as the reasons for medico-legal
      autopsy in hospital deaths. Twenty percent of the participants felt that internal
      findings at autopsy poorly matched with the case records. All the experts agreed
      that external autopsy findings matched with the hospital case records. Nearly two
      third of the participants felt that it was difficult in some cases to interpret
      the autopsy findings without case records from the hospital where the deceased
      was treated. CONCLUSION: Our findings suggest that the exercise of carrying out
      medico-legal autopsy routinely in every hospital death as evident in the Indian
      framework is often unnecessary as per the experts' opinion. Autopsy findings in
      hospital deaths often correlate with hospital case records.

PMID- 23969183
TI  - Avoiding and nonexpressing: coping styles of patients with paragangliomas.
AB  - CONTEXT: Paraganglioma (PGL) patients and succinate dehydrogenase (SDH) gene
      mutation carriers at risk for PGLs have a decreased quality of life (QoL). QoL
      may be affected by the strategy an individual uses when dealing with a stressful
      situation, ie, specific coping styles. Understanding the various approaches to
      coping may allow the development of targeted interventions to improve patient
      QoL. OBJECTIVE: The objective of the study was to assess coping styles in PGL
      patients and SDH mutation carriers. DESIGN: This was a cross-sectional study.
      SETTING: The study was conducted at a tertiary referral center. PATIENTS AND
      METHODS: Coping styles were assessed using the Utrecht Coping List. The results
      from the study cohort were compared with a control group and data derived from
      the literature. Potential differences in coping styles between the various SDH
      mutation carriers and PGL patients without an SDH mutation were explored.
      RESULTS: Of the 174 patients who responded, 122 were SDHD, 25 SDHB, and 2 SDHC
      mutation carriers. An additional 25 patients lacked an SDH mutation. They
      recruited 100 peers as controls. Compared with the general population, the study
      cohort was more avoidant of problems (P < .001) and reported less expression of
      emotion (P < .01). Compared with patients with other conditions, they sought more
      social support (P < .001). There were no significant differences in coping styles
      between the various categories of mutation carriers or PGL patients lacking a
      mutation. CONCLUSIONS: Coping styles of PGL patients and SDH mutation carriers
      differ from those of control and reference groups and include an avoidant coping
      style and a lack of emotional expression.

PMID- 23969184
TI  - Efficacy and safety of an octreotide implant in the treatment of patients with
      acromegaly.
AB  - CONTEXT: Acromegaly is caused by excessive GH secretion and IGF-I overproduction.
      The goals of treatment are to reduce GH and IGF-I values to normal and relieve
      the associated symptoms. OBJECTIVE: The purpose of this article was to
      demonstrate that an octreotide implant (84 mg) is safe and efficacious in
      patients with acromegaly who were responsive to prior monthly octreotide long
      acting release (LAR) injections. DESIGN: This was a phase 3, open-label study.
      Before treatment, subjects received a stable monthly dose of octreotide LAR
      injections (10-40 mg) for >= 3 months. Randomization was in a 3:1 ratio to either
      a 6-month octreotide implant or monthly octreotide LAR injections. SETTING: This
      was a multicenter, international study conducted in private or institutional
      practices. SUBJECTS: Enrollment included 163 subjects (aged >= 18 years) with
      acromegaly. MAIN OUTCOME MEASURE: The efficacy, safety, and tolerability of the
      octreotide implant during 24 weeks of treatment was evaluated. RESULTS: After 24
      weeks, the success rate of the implant for maintenance of IGF-I and GH levels was
      86% (95% confidence interval, 80.3%) compared with a rate of 84% (95% confidence
      interval, 73.8%) for octreotide LAR. Serum octreotide concentrations after
      implant insertion increased within 8 days and peaked between days 14 and 28. The
      overall safety of the octreotide implant and octreotide LAR were similar.
      Diarrhea and headache were more frequent with the implant, whereas cholecystitis
      and hypertension were more frequent with octreotide LAR. CONCLUSIONS: In this
      pivotal phase 3 study, the octreotide implant maintained reduced blood levels of
      GH and IGF-I with continuous octreotide release over 6 months, which was well
      tolerated.

PMID- 23969185
TI  - Increased frequency of the anti-mullerian-inhibiting hormone receptor 2 (AMHR2)
      482 A>G polymorphism in women with polycystic ovary syndrome: relationship to
      luteinizing hormone levels.
AB  - CONTEXT: The polycystic ovary syndrome (PCOS) is a common and complex disease
      without a clear pattern of inheritance. Anti-Mullerian hormone (AMH) has an
      inhibitory effect on FSH-stimulated follicle growth. Serum AMH levels are higher
      in women with PCOS than in normo-ovulatory women. The elevated AMH levels may
      reflect abnormalities in AMH signaling. OBJECTIVE: The purpose of this study was
      to evaluate the association of the anti-Mullerian hormone receptor 2 (AMHR2) -482
      A>G polymorphism (rs2002555) with the pathophysiology of PCOS. DESIGN: AMHR2 -482
      A>G polymorphism genotyping were performed in a large cohort of women with PCOS
      and in a healthy control group. SETTING/SUBJECTS: A total of 858 Caucasian Greek
      women with PCOS and 309 healthy control women were studied. INTERVENTIONS:
      Genotyping and hormonal measurements were preformed. MAIN OUTCOME MEASURES:
      Hormone levels in women with PCOS were analyzed. RESULTS: The AMHR2 polymorphism
      was more common in women with PCOS than in control women (P = .026). Homozygous
      AMHR2 -482 A>G gene polymorphisms (GG) were associated with decreased levels of
      LH (P = .003) and lower LH to FSH ratios (P = .01) in women with PCOS, as well as
      with lower prolactin levels (P = .004). No other associations related to AMHR2 
      482 A>G polymorphisms were observed in women with PCOS or control women.
      CONCLUSION: In this study, the role of the AMHR2 -482 A>G gene polymorphism in
      the pathogenesis of PCOS was suggested by the association of the variant with
      PCOS risk. Thus, further research is needed to elucidate a possible association
      of the AMHR2 -482 A>G gene polymorphism with AMH signaling and impaired ovarian
      function and its clinical significance in women with PCOS.

PMID- 23969186
TI  - Antiproliferative and proapoptotic activity of sunitinib on endothelial and
      anaplastic thyroid cancer cells via inhibition of Akt and ERK1/2 phosphorylation
      and by down-regulation of cyclin-D1.
AB  - CONTEXT: Recent experimental evidence suggests a rationale for the use of
      multitarget tyrosine kinase inhibitors for the treatment of thyroid cancers.
      Sunitinib showed promising preliminary results against anaplastic thyroid cancer
      (ATC), and it has been used for some patients who are ineligible for clinical
      trials. OBJECTIVES: The aims of this study were to investigate the in vitro and
      in vivo activity of sunitinib on ATC and on microvascular endothelial cells and
      the molecular mechanism for the observed sunitinib activity. METHODS:
      Proliferation and apoptotic assays were performed on human dermal microvascular
      endothelial and on BRAF- or H-ras-mutated ATC cells (8305C and FB3, respectively)
      after in vitro exposure to sunitinib for 72 hours. Vascular endothelial growth
      factor receptor-2, epithelial growth factor receptor, ERK1/2, and Akt
      phosphorylation was quantified by ELISA and Western blot. Cyclin-D1 mRNA
      expression was evaluated by real-time PCR, and cyclin-D1 intracellular
      concentrations were measured by ELISA. 8305C tumor xenografts in nude mice were
      treated with sunitinib at 50 mg/kg/d (i.p.). RESULTS: Antiproliferative and
      proapoptotic activity of sunitinib was observed in both endothelial and ATC
      cells. Phospho-vascular endothelial growth factor receptor-2 levels significantly
      decreased after sunitinib treatment in activated endothelial cells. Phospho
      epidermal growth factor receptor, ERK1/2, and Akt phosphorylation was
      significantly inhibited by sunitinib treatment in endothelial and cancer cells,
      and cyclin-D1 mRNA and protein expression was inhibited. Sunitinib administration
      in vivo caused significant inhibition of tumor growth (P < .05). CONCLUSIONS:
      Sunitinib is active in vitro and in vivo against activated endothelial and ATC
      cells via the inhibition of Akt and ERK1/2 phosphorylation and through the down
      regulation of cyclin-D1.

PMID- 23969187
TI  - Metreleptin improves blood glucose in patients with insulin receptor mutations.
AB  - CONTEXT: Rabson-Mendenhall syndrome (RMS) is caused by mutations of the insulin
      receptor and results in extreme insulin resistance and dysglycemia. Hyperglycemia
      in RMS is very difficult to treat, and patients are at risk for early morbidity
      and mortality from complications of diabetes. OBJECTIVE: Our objective was to
      study 1-year effects of recombinant human methionyl leptin (metreleptin) in 5
      patients with RMS and 10-year effects in 2 of these patients. DESIGN AND SETTING:
      We conducted an open-label nonrandomized study at the National Institutes of
      Health. PATIENTS: Patients were adolescents with RMS and poorly controlled
      diabetes. INTERVENTION: Two patients were treated with escalating doses (0.02 up
      to 0.22 mg/kg/d) of metreleptin for 10 years, including 3 cycles of metreleptin
      withdrawal and reinitiation. In all 5 patients, 1-year effects of metreleptin
      (0.22 mg/kg/d) were studied. OUTCOME MEASURES: Hemoglobin A1c (HbA1c) and body
      mass index (BMI) z-scores were evaluated every 6 months. RESULTS: HbA1c decreased
      from 11.4% +/- 1.1% at baseline to 9.3% +/- 1.9% after 6 months and 9.7% +/- 1.6%
      after 12 months of metreleptin (P = .007). In patients treated for 10 years,
      HbA1c declined with each cycle of metreleptin and rose with each withdrawal. BMI
      z-scores declined from -1.4 +/- 1.8 at baseline, to -2.6 +/- 1.6 after 12 months
      of metreleptin (P = .0006). Changes in BMI z-score correlated with changes in
      HbA1c (P < .0001). CONCLUSIONS: Metreleptin treatment for 12 months was
      associated with a 1.7% reduction in HbA1c; part of this improvement was likely
      mediated via decreased BMI. Metreleptin is a promising treatment option for RMS,
      but additional therapies are needed to achieve HbA1c targets.

PMID- 23969188
TI  - Does BRAF V600E mutation predict aggressive features in papillary thyroid cancer?
      Results from four endocrine surgery centers.
AB  - BACKGROUND: Existing evidence is controversial regarding the association between
      BRAF mutation status and aggressive features of papillary thyroid cancer (PTC).
      Specifically, no study has incorporated multiple surgical practices performing
      routine central lymph node dissection (CLND) and thus has patients who are truly
      evaluable for the presence or absence of central lymph node metastases (CLNMs).
      METHODS: Consecutive patients who underwent total thyroidectomy and routine CLND
      at 4 tertiary endocrine surgery centers were retrospectively reviewed.
      Descriptive and bivariable analyses examined demographic, patient, and tumor
      related factors. Multivariable analyses examined the odds of CLNM associated with
      positive BRAF status. RESULTS: In patients with classical variant PTC, bivariate
      analysis found no significant associations between BRAF mutation and aggressive
      clinicopathologic features; multivariate analysis demonstrated that BRAF status
      was not an independent predictor of CLNM. When all patients with PTC were
      analyzed, including those with aggressive or follicular subtypes, bivariate
      analysis showed BRAF mutation to be associated with LNM, advanced American Joint
      Committee on Cancer (AJCC) stage, and histologic subtype. Multivariable analyses
      showed BRAF, age, size, and extrathyroidal extension to be associated with CLNM.
      CONCLUSION: Although BRAF mutation was found to be an independent predictor of
      central LNM in the overall cohort of patients with PTC, this relationship lost
      significance when only classical variant PTC was included in the analysis. The
      usefulness of BRAF in predicting the presence of LNM remains questionable.
      Prospective studies are needed before BRAF mutation can be considered a reliable
      factor to guide the treatment of patients with PTC, specifically whether to
      perform prophylactic CLND.

PMID- 23969189
TI  - Catastrophic bone deformities associated with primary hyperparathyroidism in a
      middle-aged man.

PMID- 23969190
TI  - Testicular adrenal rest tumors develop independently of long-term disease
      control: a longitudinal analysis of 50 adult men with congenital adrenal
      hyperplasia due to classic 21-hydroxylase deficiency.
AB  - CONTEXT: Testicular adrenal rest tumors (TARTs) and hypogonadotropic hypogonadism
      are the two most common causes for male infertility in classic 21-hydroxylase
      deficiency. Current hypotheses suggest the quality of disease control to be one
      of the main pathogenic factors for TART development. OBJECTIVE: The aim was to
      study long-term predictors for TART development in a retrospective longitudinal
      study. DESIGN: Fifty men with classic 21-hydroxylase deficiency (31 salt wasting,
      19 simple virilizing) were investigated. Testicular ultrasound at a median age at
      investigation of 27 years detected TARTs in 28 of 50 subjects (19 salt wasting, 9
      simple virilizing). TART presence was correlated with long-term parameters of
      disease control during childhood and adolescence obtained from patients' charts:
      24-hour urine pregnanetriol, serum 17-hydroxyprogesterone, onset and stage of
      pubic hair development, testicular growth, and bone age in relation to
      chronological age. RESULTS: There was no difference in pregnanetriol excretion
      over lifetime between patients with and without TARTs. Similarly, neither
      development of pubic hair and testicular volume (Tanner) nor bone age in relation
      to chronological age differed between the two groups. Furthermore, the two groups
      had the same body mass index and the same impairment of final height in relation
      to midparental target height. CONCLUSION: Our longitudinal analysis demonstrates
      no association between TART presence and parameters of disease control. These
      data, therefore, argue for other mechanisms more relevant for TART induction
      including those occurring during fetal development.

PMID- 23969191
TI  - The antifungal activity of fatty acids of all stages of Sarcophaga carnaria L.
      (Diptera: Sarcophagidae).
AB  - Fatty acids as components of cuticular lipids of insects play a significant role
      in antifungal in protection against fungal infection. The chemical composition of
      cuticular and internal extracts obtained from all developmental stages of flesh
      flies Sarcophaga carnaria was identified. The fatty acids were detected using gas
      chromatography coupled with mass spectrometry and the most abundant for all
      examined stages were: 18:1 > 16:0 > 16:1 > 18:0 > 18:2. Polyunsaturated fatty
      acids (PUFA) C20 were found in both, cuticular and internal extracts. GC-MS
      analysis showed higher relative content of PUFA in adults than in preimaginal
      stages. Fatty acids alone as well as their cuticular and internal extracts
      obtained from larvae, pupae male and female of S. carnaria were tested according
      to their potential antimicrobial activity against entomopathogenic fungi:
      Paecilomyces lilacinus, Paecilomyces fumosoroseus, Lecanicillium lecanii,
      Metarhizium anisopliae, Beauveria bassiana (Tve-N39) and B. bassiana (Dv-1/07).
      FA presented diverse antimicrobial activity depending on the length of the chain
      and the presence of unsaturated bonds. Short chain and unsaturated FA (6:0, 11:0,
      13:0) have shown significantly stronger activity against fungi but they were
      detected in lower concentrations. PUFA inhibit fungal growth more effectively
      than unsaturated long chain fatty acids. Cuticular and internal extracts of all
      living forms of S. carnaria exhibited approximately equal activity against tested
      entomopathogenic fungi. We presumed that the most abundant saturated long chain
      FA and additionally PUFA founded in our analysis are involved in protecting the
      flies against fungal infection.

PMID- 23969192
TI  - Infection prevention and control strategies in the era of limited resources and
      quality improvement: a perspective paper.
AB  - This paper aims to describe, using an evidence-based approach, the importance of
      and the resources necessary for implementing effective infection prevention and
      control (IPC) programmes. The intrinsic and explicit values of such strategies
      are presented from a clinical, health-economic and patient safety perspective.
      Policy makers and hospital managers are committed to providing comprehensive,
      accessible, and affordable healthcare of high quality. Changes in the healthcare
      system over time accompanied with variations in demographics and case-mix have
      considerably affected the availability, quality and ultimately the safety of
      healthcare. The main goal of an IPC programme is to prevent and control
      healthcare-associated infections (HAI). Many patient-, healthcare provider-, and
      organizational factors are associated with an increased risk for acquiring HAIs
      and may impact both the quality and outcome of patient care. Evidence has been
      published in support of having an effective IPC programme. It has been estimated
      that about one-third of HAIs could be prevented if key elements of the evidence
      based recommendations for IPC are adequately introduced and followed. However,
      several healthcare agencies from over the world have reported deficits in the
      essential resources and components of current IPC programmes. To meet its main
      goal, staffing, training, and infrastructure requirements are needed.
      Nevertheless, and given the economic crisis, policy makers and hospital managers
      may be tempted to not increase or even to reduce the budget as it consumes
      resources and does not generate sufficient visible revenue. IPC is a critical
      issue in patient safety, as HAIs are by far the most common complication
      affecting admitted patients. The significant clinical and health-economic burden
      HAIs place on the healthcare system speak to the importance of getting introduced
      effective IPC programmes. 

PMID- 23969193
TI  - Signal integral for optimizing the timing of defibrillation.
AB  - OBJECTIVE: The possibility of successful defibrillation decreases with an
      increased duration of ventricular fibrillation (VF). Futile electrical shocks are
      inversely correlated with myocardial contractile function and long-term survival.
      Previous studies have demonstrated that various ECG waveform analyses predict the
      success of defibrillation. This study investigated whether the absolute amplitude
      of pre-shock VF waveform is likely to predict the success of defibrillation.
      METHODS: ECG recordings of 350 out-of-hospital cardiac arrest (OOHCA) patients
      were obtained from the automated external defibrillator (AED) and analyzed by the
      method of signal integral. Successful defibrillation was defined as organized
      rhythm with heart rate >=40beat/min commencing within one min of post-shock
      period and persisting for a minimum of 30s. RESULTS: Signal integral was
      significantly greater in successful defibrillation than unsuccessful
      defibrillation (81.76+/-32.3mV vs. 34.9+/-15.33mV, p<0.001). The intersection of
      the sensitivity and specificity curve provided a threshold value of 51mV. The
      corresponding values of sensitivity, specificity, positive predictive and
      negative predictive values for successful defibrillation were 90%, 86%, 80% and
      93%, respectively. The receiver operator curve further revealed that signal
      integral predicted the likelihood of successful defibrillation (area under the
      curve=0.949). CONCLUSIONS: Signal integral predicted successful electrical shocks
      on patients with ventricular fibrillation and have potential to optimize the
      timing of defibrillation and reduce the number of electrical shocks.

PMID- 23969194
TI  - Gambling against neglect: unconscious spatial biases induced by reward
      reinforcement in healthy people and brain-damaged patients.
AB  - Orienting attention in space recruits fronto-parietal networks whose damage
      results in unilateral spatial neglect. However, attention orienting may also be
      governed by emotional and motivational factors; but it remains unknown whether
      these factors act through a modulation of the fronto-parietal attentional systems
      or distinct neural pathways. Here we asked whether attentional orienting is
      affected by learning about the reward value of targets in a visual search task,
      in a spatially specific manner, and whether these effects are preserved in right
      brain damaged patients with left spatial neglect. We found that associating
      rewards with left-sided (but not right-sided) targets during search led to
      progressive exploration biases towards left space, in both healthy people and
      neglect patients. Such spatially specific biases occurred even without any
      conscious awareness of the asymmetric reward contingencies. These results show
      that reward-induced modulations of space representation are preserved despite a
      dysfunction of fronto-parietal networks associated with neglect, and therefore
      suggest that they may arise through spared subcortical networks directly acting
      on sensory processing and/or oculomotor circuits. These effects could be usefully
      exploited for potentiating rehabilitation strategies in neglect patients. 

PMID- 23969195
TI  - Neural correlates of the relationship between discourse coherence and sensory
      monitoring in schizophrenia.
AB  - Unusual language use is a core feature of psychosis, but the nature and
      significance of this are not understood. In particular, thought disorder in
      schizophrenia (SZ) is characterized by markedly bizarre speech, but the cognitive
      components that contribute to this and the brain correlates of these components
      are unknown. A number of studies have demonstrated language abnormalities in
      single word processing, but few have examined speech in SZ at the discourse
      level. This has been at least partly due to the difficulty in quantifying content
      of discourse. Recently, methods in computational linguistics have been found to
      be useful for detecting differences in semantic coherence during discourse
      between different clinical groups. We build on this work by demonstrating how
      these methods can be combined with funtional magnetic resonance imaging (fMRI) in
      order to tease apart factors that underlie free discourse and its deviations, and
      how they relate to brain activity. Eleven volunteers with SZ and eleven controls
      participated in an interview during which they were asked to talk as much as they
      could about 'religious belief'. These same participants underwent fMRI during a
      word monitoring task, during which modality of monitoring was manipulated by
      varying the congruence of auditory and visual stimuli. Semantic coherence scores,
      measured from free discourse, were examined for their relationship to brain
      activations during fMRI. In healthy controls, regions associated with executive
      function were related to coherence. In persons with SZ, coherence was mainly
      related to auditory and visual regions, depending on the modality of monitoring,
      but superior/middle temporal cortex related to coherence regardless of task.
      These findings are consistent with existing evidence for a role of superior
      temporal cortex in thought disorder, and demonstrate that computational measures
      of semantic content capture objective measures of coherence in speech that can be
      usefully related to underlying neurophysiological processes. 

PMID- 23969196
TI  - GABA(A) receptor chloride channels are involved in the neuroprotective role of
      GABA following oxygen and glucose deprivation in the rat cerebral cortex but not
      in the hippocampus.
AB  - Assays on "ex vivo" sections of rat hippocampus and rat cerebral cortex,
      subjected to oxygen and glucose deprivation (OGD) and a three-hour reperfusion
      like (RL) recovery, were performed in the presence of either GABA or the GABA(A)
      receptor binding site antagonist, bicuculline. Lactate dehydrogenase (LDH) and
      propidium iodide were used to quantify cell mortality. We also measured, using
      real-time quantitative polymerase chain reaction (qPCR), the early
      transcriptional response of a number of genes of the glutamatergic and GABAergic
      systems. Specifically, glial pre- and post-synaptic glutamatergic transporters
      (namely GLAST1a, EAAC-1, GLT-1 and VGLUT1), three GABAA receptor subunits
      (alpha1, beta2 and gamma2), and the GABAergic presynaptic marker, glutamic acid
      decarboxylase (GAD65), were studied. Mortality assays revealed that GABAA
      receptor chloride channels play an important role in the neuroprotective effect
      of GABA in the cerebral cortex, but have a much smaller effect in the
      hippocampus. We also found that GABA reverses the OGD-dependent decrease in
      GABA(A) receptor transcript levels, as well as mRNA levels of the membrane and
      vesicular glutamate transporter genes. Based on the markers used, we conclude
      that OGD results in differential responses in the GABAergic presynaptic and
      postsynaptic systems.

PMID- 23969197
TI  - Regional homogeneity of resting-state fMRI contributes to both neurovascular and
      task activation variations.
AB  - The task induced blood oxygenation level dependent signal changes observed using
      functional magnetic resonance imaging (fMRI) are critically dependent on the
      relationship between neuronal activity and hemodynamic response. Therefore,
      understanding the nature of neurovascular coupling is important when interpreting
      fMRI signal changes evoked via task. In this study, we used regional homogeneity
      (ReHo), a measure of local synchronization of the BOLD time series, to
      investigate whether the similarities of one voxel with the surrounding voxels are
      a property of neurovascular coupling. FMRI scans were obtained from fourteen
      subjects during bilateral finger tapping (FTAP), digit-symbol substitution (DSST)
      and periodic breath holding (BH) paradigm. A resting-state scan was also obtained
      for each of the subjects for 4min using identical imaging parameters. Inter-voxel
      correlation analyses were conducted between the resting-state ReHo, resting-state
      amplitude of low frequency fluctuations (ALFF), BH responses and task activations
      within the masks related to task activations. There was a reliable mean voxel
      wise spatial correlation between ReHo and other neurovascular variables (BH
      responses and ALFF). We observed a moderate correlation between ReHo and task
      activations (FTAP: r=0.32; DSST: r=0.22) within the task positive network and a
      small yet reliable correlation within the default mode network (DSST: r=-0.08).
      Subsequently, a linear regression was used to estimate the contribution of ReHo,
      ALFF and BH responses to the task activated voxels. The unique contribution of
      ReHo was minimal. The results suggest that regional synchrony of the BOLD
      activity is a property that can explain the variance of neurovascular coupling
      and task activations; but its contribution to task activations can be accounted
      for by other neurovascular factors such as the ALFF. 

PMID- 23969198
TI  - 3.0T MR investigation of CLIPPERS: role of susceptibility weighted and perfusion
      weighted imaging.
AB  - For the first time we describe and interpret Susceptibility Weighted Imaging
      (SWI) and Perfusion Weighted Imaging (PWI) findings in a case of Chronic
      Lymphocytic Inflammation with Perivascular Pontine Enhancement Responsive to
      Steroids (CLIPPERS). The diagnosis of the disease was formulated on the basis of
      typical Magnetic Resonance (MR) findings and its responsiveness to steroids in a
      40-year-old man with acute onset of dizziness, ataxia and diplopia. The patient
      underwent a 3 tesla (T) MR examination including SWI and PWI sequences. SWI
      revealed prominent veins and multiple hypointense lesions of different size
      widely distributed in brainstem and cerebellum, which could be expression of iron
      deposition or cellular infiltrates. PWI demonstrated global infratentorial
      hypoperfusion. SWI and PWI provide new information on CLIPPERS that might be
      helpful to understand the physiopathology of the disease. Further observations
      are needed to evaluate if these findings are peculiar for CLIPPERS and if they
      might have a role in a non-invasive diagnosis of the disease.

PMID- 23969199
TI  - 3 TESLA MR imaging in adults with focal onset epilepsy.
AB  - OBJECTIVE: The finding of cerebral epileptogenic lesions in magnetic resonance
      (MR) has demonstrated to be a relevant prognostic factor for potential surgical
      candidates. In a series of consecutive adults with focal onset epilepsy, we
      investigated the yield of 3T MR imaging for detecting epileptogenic cerebral
      lesions. MATERIALS AND METHODS: We prospectively recruited 161 adult patients
      with a diagnosis of focal epilepsy, all of whom underwent standardized MR imaging
      study performed with a 3T magnet. RESULTS: Lesion-related epilepsy was observed
      in 48% of patients, and 12% of cryptogenic patients showed subtle or non-specific
      lesions related to the epileptogenic source. The most common findings were focal
      cortical dysplasia and vascular lesions, followed by mesial temporal sclerosis,
      tumors, and scars from previous cerebral injuries. Patients older than 72 years
      were more likely to have vascular epilepsy. CONCLUSIONS: Diagnostic assessment
      using a standardized 3T MR imaging protocol for focal-onset epilepsy detects
      lesions in nearly half the patients. Our results indicate that elders with focal
      epilepsy should be searched for vascular lesions.

PMID- 23969200
TI  - The number of regulatory T cells in transbronchial lung allograft biopsies is
      related to FoxP3 mRNA levels in bronchoalveolar lavage fluid and to the degree of
      acute cellular rejection.
AB  - BACKGROUND: The transcription factor Forkhead Box P3 (FoxP3) is a marker of
      regulatory T cells (Tregs) - a subset of T cells known to suppress a wide range
      of immune responses. These cells are considered to be pivotal for the induction
      of tolerance to donor antigens in human allografts. We aimed to correlate the
      number of lymphocytes expressing FoxP3 in transbronchial biopsies from lung
      allografts with the FoxP3 expression in bronchoalveolar lavage fluid (BALF). In
      addition, we aimed to correlate the number of FoxP3+ cells in transbronchial
      biopsies with the degree of acute cellular rejection in lung allografts.
      MATERIALS AND METHODS: The expression of FoxP3 was evaluated using
      immunohistochemical staining in 40 lung allograft biopsies obtained from 23
      patients. The number of Tregs was related to the FoxP3 mRNA levels as determined
      using qRT-PCR in corresponding BALF samples from the same patients. Furthermore,
      the number of Tregs was related to the degree of acute allograft rejection
      (according to ISHLT criteria, A0-A4). RESULTS: Regression analysis showed a
      significant concordance between the number of Tregs in lung tissue and the level
      of FoxP3 mRNA relative to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA
      levels in BALF (n=40, p=0.0001). In addition, we found a significant increase in
      the number of Tregs during acute allograft rejections of grades A2 and higher
      (median: 32.6Tregs/mm(2)) when compared to those of grades A1 and A0 (median:
      4.9Tregs/mm(2)) (p=0.0002). DISCUSSION AND CONCLUSION: The association between
      the distribution of Tregs in transbronchial biopsies and the level of FoxP3 mRNA
      in BALF indicates that assessment of FoxP3 mRNA in BALF is a reliable non
      invasive method for evaluating the number of Tregs in lung tissue. Furthermore,
      the association between the number of Tregs in lung tissue and the degree of
      acute cellular rejection shows that Tregs are recruited to the site of
      inflammation and may be involved in the regulation of acute rejection. Thus,
      Tregs may play a role in the cellular processes that affect lung allograft
      outcome.

PMID- 23969201
TI  - Which drug-induced side effects would be tolerated in the prospect of seizure
      control?
AB  - There is ample evidence that side effects of antiepileptic pharmacotherapy
      negatively affect quality of life, adherence, and long-term retention. The study
      was set up to evaluate the anticipated tolerance of common side effects provided
      that a 50% or 100% reduction of seizure frequency would be achieved. An anonymous
      inquiry in 79 consecutive patients with epilepsy comprised questions regarding
      the severity of epilepsy/seizures and the perceived impact of seizures and drug
      treatment on daily functioning and a 10-tiered rating which assesses 11 common
      behavioral/psychiatric, cognitive, physiological, or physical side effects
      according to the degree to which they would be tolerated. Least acceptance was
      evident for psychiatric side effects followed by cognitive, physiological, and
      physical side effects. Weight gain and tiredness were the most tolerated side
      effects. The overall low acceptance of negative side effects was slightly higher
      in the case of a 100% vs. 50% seizure frequency reduction (28% vs. 21% of the
      maximum toleration score regarding all side effects). Surely, there is a trade
      off between the severity of epilepsy, seizure control, and the acceptance of
      adverse treatment effects. However, the data disclose that psychiatric and
      cognitive side effects are least accepted. Thus, consideration of individual
      tolerance and monitoring of side effects in addition to seizures may increase
      adherence and therapy success. 

PMID- 23969202
TI  - Increased ratio of glutamate/glutamine to creatine in the right hippocampus
      contributes to depressive symptoms in patients with epilepsy.
AB  - PURPOSE: Our study aimed to investigate whether the glutamatergic system in the
      hippocampus is correlated with depressive symptoms in patients with epilepsy.
      METHODS: Fifty patients with epilepsy were recruited and divided into three
      groups on the basis of their Hamilton Depression Rating Scale (HAMD) scores.
      Single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) was carried out.
      Pearson correlation analysis and multiple linear regression analysis were
      performed to investigate any correlation between the variables of hippocampal
      metabolites and HAMD scores. RESULTS: Proton magnetic resonance spectroscopy
      analysis showed that the ratio of glutamate/glutamine to creatine (Glx/Cr) in the
      right hippocampus was significantly increased in patients with moderate
      depression and correlated positively with HAMD scores. Multiple linear regression
      analysis showed that the ratio of Glx/Cr in the right hippocampus was an
      independent risk factor relating to depressive symptoms in patients with
      epilepsy. CONCLUSION: A disturbance of the hippocampal glutamatergic system may
      be involved in the pathogenesis of depression in epilepsy.

PMID- 23969203
TI  - Psychiatric disorders in patients with psychogenic nonepileptic seizures and drug
      resistant epilepsy: a study of an Argentine population.
AB  - Epidemiological data show that up to 20-30% of patients with psychogenic
      nonepileptic seizures (PNESs), resembling drug-resistant epilepsy (DRE), are
      referred to tertiary epilepsy centers. Furthermore, both disorders present high
      psychiatric comorbidity, and video-EEG is the gold standard to make differential
      diagnoses. In this study, we described and compared the clinical presentation and
      the frequency of psychiatric disorders codified in DSM IV in two groups of
      patients, one with PNESs and the other with DRE, admitted in a tertiary care
      epilepsy center of Buenos Aires, Argentina. We included 35 patients with PNESs
      and 49 with DRE; all were admitted in the video-EEG unit in order to confirm an
      epilepsy diagnosis and determine surgical treatment possibilities. All patients
      underwent a neurological and psychiatric assessment, according to standardized
      protocol (SCID I and II; DSM IV criteria). Student's t test was performed to
      compare continuous variables and Chi square test to compare qualitative
      variables. In this study, 33 (67%) patients with DRE and 35 (100%) patients with
      PNESs met criteria for at least one disorder codified in Axis I of DSM IV
      (p=0.003). Differences in the frequency of psychiatric disorder presentation were
      found between groups. Anxiety disorders (16.32% vs 40%; p=0.015), trauma history
      (24.5% vs 48.57%; p=0.02), posttraumatic stress disorder (4.08% vs 22.85%;
      p=0.009), and personality cluster B disorders (18.37% vs 42.86%; p=0.02) were
      more frequent in the group with PNESs. Psychotic disorders were more frequent in
      the group with DRE (20.4% vs 2.85%; p=0.019). Depression was equally prevalent in
      both groups. Standardized psychiatric assessment provides information that could
      be used by the mental health professional who receives the referral in order to
      improve quality of care and smooth transitions to proper PNES treatment, which
      should include a multidisciplinary approach including neurology and psychiatry. 

PMID- 23969205
TI  - Neurochemistry of myenteric plexus neurons of bank vole (Myodes glareolus) ileum.
AB  - The neurochemistry of enteric neurons differs among species of small laboratory
      rodents (guinea-pig, mouse, rat). In this study we characterized the phenotype of
      ileal myenteric plexus (MP) neuronal cells and fibers of the bank vole (Myodes
      glareolus), a common rodent living in Europe and in Northern Asia which is also
      employed in prion experimental transmission studies. Six neuronal markers were
      tested: choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS),
      calbindin (CALB), calcitonin gene-related peptide (CGRP) and substance P (SP),
      along with HuC/D as a pan-neuronal marker. Neurons expressing ChAT- and nNOS
      immunoreactivity (IR) were 36 +/- 12% and 24 +/- 5%, respectively. Those
      expressing CGRP-, SP- and CALB-IR were 3 +/- 3%, 21 +/- 5% and 6 +/- 2%,
      respectively. Therefore, bank vole MPs differ consistently from murine MPs in
      neurons expressing CGRP-, SP- and CALB-IR. These data may contribute to define
      the prion susceptibility of neuron cell populations residing within ileal MPs
      from bank voles, along with their morpho-functional alterations following oral
      experimental prion challenge.

PMID- 23969206
TI  - USA missing opportunities for HPV vaccination.

PMID- 23969204
TI  - Novel immunogenic baculovirus expressed virus-like particles of foot-and-mouth
      disease (FMD) virus protect guinea pigs against challenge.
AB  - Vaccination is a well accepted strategy for control of foot-and-mouth disease
      (FMD) in endemic countries. Currently, chemically inactivated virus antigens are
      used for preparation of FMD vaccine. To develop a non-infectious and safe
      recombinant vaccine, we expressed structural polypeptide of FMDV (O/IND/R2/75)
      using baculovirus expression system. We show that inclusion of mutated viral 3C
      protease in frame with the polypeptide (P1-2A), enhanced the yield of structural
      proteins. The structural proteins retained antigenicity and assembled into empty
      virus-like particles (VLPs). Immunization of guinea pigs with purified fractions
      of the VLPs resulted in humoral and cell mediated immune response by 4 weeks. The
      VLPs elicited comparable humoral immune response and relatively higher cell
      mediated immune response, when compared to conventional vaccine in guinea pigs.
      Further, up to 70% of the VLP immunized guinea pigs were protected against
      challenge with homologous guinea pig adapted virus. Our results highlight the
      application of recombinant FMDV VLPs in FMD vaccination.

PMID- 23969207
TI  - Do we need new drugs against human African trypanosomiasis?

PMID- 23969208
TI  - Community-associated MRSA from the Indian subcontinent.

PMID- 23969209
TI  - Studies of selective decontamination.

PMID- 23969210
TI  - Studies of selective decontamination.

PMID- 23969211
TI  - Studies of selective decontamination - Authors' reply.

PMID- 23969212
TI  - Selective digestive decontamination and bacterial resistance.

PMID- 23969213
TI  - Selective digestive decontamination and bacterial resistance - Authors' reply.

PMID- 23969214
TI  - Laboratory monitoring for antiretroviral therapy in low-resource settings.

PMID- 23969215
TI  - Cheryl Jones: cracking mysteries in paediatric infection.

PMID- 23969217
TI  - The emergence of influenza A H7N9 in human beings 16 years after influenza A
      H5N1: a tale of two cities.
AB  - Infection with either influenza A H5N1 virus in 1997 or avian influenza A H7N9
      virus in 2013 caused severe pneumonia that did not respond to typical or atypical
      antimicrobial treatment, and resulted in high mortality. Both viruses are
      reassortants with internal genes derived from avian influenza A H9N2 viruses that
      circulate in Asian poultry. Both viruses have genetic markers of mammalian
      adaptation in their haemagglutinin and polymerase PB2 subunits, which enhanced
      binding to human-type receptors and improved replication in mammals,
      respectively. Hong Kong (affected by H5N1 in 1997) and Shanghai (affected by H7N9
      in 2013) are two rapidly flourishing cosmopolitan megacities that were increasing
      in human population and poultry consumption before the outbreaks. Both cities are
      located along the avian migratory route at the Pearl River delta and Yangtze
      River delta. Whether the widespread use of the H5N1 vaccine in east Asia-with
      suboptimum biosecurity measures in live poultry markets and farms-predisposed to
      the emergence of H7N9 or other virus subtypes needs further investigation. Why
      H7N9 seems to be more readily transmitted from poultry to people than H5N1 is
      still unclear. 

PMID- 23969218
TI  - Pyogenic liver abscess caused by Streptococcus mitis.

PMID- 23969219
TI  - The Journal of Visceral Surgery has doubled its impact factor in just two years!

PMID- 23969216
TI  - Clinical epidemiology of the global expansion of Klebsiella pneumoniae
      carbapenemases.
AB  - Klebsiella pneumoniae carbapenemases (KPCs) were originally identified in the USA
      in 1996. Since then, these versatile beta-lactamases have spread internationally
      among Gram-negative bacteria, especially K pneumoniae, although their precise
      epidemiology is diverse across countries and regions. The mortality described
      among patients infected with organisms positive for KPC is high, perhaps as a
      result of the limited antibiotic options remaining (often colistin, tigecycline,
      or aminoglycosides). Triple drug combinations using colistin, tigecycline, and
      imipenem have recently been associated with improved survival among patients with
      bacteraemia. In this Review, we summarise the epidemiology of KPCs across
      continents, and discuss issues around detection, present antibiotic options and
      those in development, treatment outcome and mortality, and infection control. In
      view of the limitations of present treatments and the paucity of new drugs in the
      pipeline, infection control must be our primary defence for now. 

PMID- 23969220
TI  - [Chronic medications in the preoperative period: should they be stopped?].
AB  - As different specialists are becoming increasingly involved in the preoperative
      management of our patients (for two main reasons; Primary Care doctors have to
      perform minor surgical procedures, and as coordination between Primary Care and
      In-hospital Care is more and more necessary in order to improve their outcomes),
      we believe that an update is needed as regards the management of chronic
      medications in this period. We will try to review the current literature dealing
      with the recommendations about withdrawing or continuing these drugs. 

PMID- 23969221
TI  - Management of large coronary dissection after STAR.
AB  - The guided-STAR technique is an alternative anterograde approach for treatment of
      coronary chronic total occlusion (CTO) and it is usually followed by implantation
      of multiple stents. We describe a case of residual long coronary dissection left
      unstented after guided-STAR, with good results at 2months follow-up. This case
      emphasizes the fact that sometimes even the longest coronary dissections can be
      left unstented especially in the contest of a CTO. 

PMID- 23969222
TI  - Two-year follow-up of percutaneous coronary intervention using EucaTax or Cypher.
AB  - BACKGROUND: The EucaTax stent (EUPES) is a coronary stent with biodegradable
      polymer and camouflage coating that has been developed to promote the complete
      elution of drugs and decrease the risk of late complications. The aim of this
      study was to evaluate the efficacy and safety of the double-coated EUPES in
      patients with stable angina versus sirolimus-eluting stent CYPHER (SES) with
      permanent polymer coating. METHODS AND MATERIALS: The study included consecutive
      patient with at least 70% de novo coronary lesions in one or two native coronary
      arteries and who had undergone the coronary stenting using either EUPES or SES.
      We evaluated the 2-year major adverse cardiac events (MACE) rates, including
      total death (cardiac, non-cardiac), myocardial infarction (MI), target lesion
      revascularisation (TLR) and stent thrombosis. RESULTS: Between 2006 and 2009 this
      observational, prospective, single centre study included 602 patients (282 with
      EUPES and 320 with SES). At 2years, the rates of TLR (16.3% versus 6.25%;
      p=0.0001) and MACE (18.4% versus 7.8%; p=0.001) were significantly higher in the
      EUPES than in the SES group. The rate of TLR was significantly higher in the
      EUPES group compared with SES group in stenting of artery with a diameter less
      than 3mm, using stent length more than 18mm, as well as when the residual
      stenosis was more than 12%. CONCLUSIONS: We found that EUPES was inferior to SES
      during the 2-year follow-up with respect to rates of MACE and TLR that were
      significantly higher in the EUPES than in the SES group.

PMID- 23969223
TI  - C-reactive protein and prognosis in women and men with coronary artery disease
      after percutaneous coronary intervention.
AB  - BACKGROUND: Sex-based differences in the association between C-reactive protein
      (CRP) and cardiovascular events in patients with coronary artery disease (CAD)
      are incompletely investigated. We investigated whether there are gender
      differences in the association between CRP and outcome in patients with CAD after
      percutaneous coronary intervention (PCI). METHODS: This study included 13,170
      consecutive patients with CAD: 10,098 men and 3072 women. CRP was measured on
      admission in all patients. The primary outcome was 1-year mortality. RESULTS: CRP
      level (median [25th-75th percentiles]) was higher in women than in men (3.08
      [1.30-8.37] mg/L vs 2.30 [0.92-6.47] mg/L; P<0.001). CRP was >3mg/L in 4250 men
      (42.1%) and 1554 women (50.6%; P<0.001). One-year mortality was 4.9% (n=641
      deaths). Deaths occurred in 318 men with CRP >3mg/L and 122 men with CRP <=3mg/L
      (mortality estimates 7.7% and 2.1%, P<0.001) and in 154 women with CRP >3mg/L and
      47 women with CRP <=3mg/L (mortality estimates 10.1% and 3.2%, P<0.001). After
      adjustment in the Cox model, CRP was associated with increased risk of mortality
      in women (adjusted hazard ratio [HR]=1.03, 95% confidence interval [CI] 1.01
      1.04, P<0.001 for each 5mg/L increase) and in men (adjusted HR=1.02 [1.01-1.03],
      P<0.001, for each 5mg/L increase). CRP predicted mortality with an area under the
      receiver-operating characteristic curve =0.721, [0.683-0.760] in women and 0.732,
      [0.707-0.757] in men (P=0.659). CONCLUSIONS: Elevated CRP levels provide similar
      prognostic information in men and women with CAD after PCI which is independent
      and supplementary to that provided by conventional cardiovascular risk factors.

PMID- 23969224
TI  - Coronary artery bypass graft surgery using the radial artery as a secondary
      conduit improves patient survival.
AB  - BACKGROUND: The clinical benefits of the left internal thoracic artery-to-left
      anterior descending coronary artery graft are well established in coronary artery
      bypass graft surgery (CABG). However, limited data are available regarding the
      long-term outcome of the radial artery (RA) as a secondary conduit over the
      established standard of the saphenous venous graft. METHODS AND RESULTS: We
      compared the 12-year survival outcome in a set of propensity-matched CABG
      patients who received either the RA or the saphenous vein as a secondary conduit.
      A multivariable logistic regression that included 18 baseline characteristics was
      used to define the propensity of receiving an RA graft. The propensity model
      resulted in 260 matched pairs who underwent first-time isolated CABG from 1996 to
      2001 with similar preoperative characteristics (C statistic=0.86). The cumulative
      12-year survival estimated by use of the Kaplan-Meier method was higher for the
      RA graft patients (hazard ratio 0.76; P=0.03). This survival advantage was
      especially significant in diabetics (P=0.005), in women (P=0.02), and in the
      elderly (P=0.04.) The protective effect appeared beginning at year 5 post
      surgical intervention. CONCLUSION: The RA as a secondary conduit provided
      superior long-term survival after CABG, especially in diabetic patients, women,
      and the elderly. This effect was most pronounced >5 years after surgery.

PMID- 23969225
TI  - MicroRNA based treatment of cardiomyopathy: not all dystrophies are created
      equal.

PMID- 23969226
TI  - Microbiota abnormalities in inflammatory airway diseases - Potential for therapy.
AB  - Increasingly the development of novel therapeutic strategies is taking into
      consideration the contribution of the intestinal microbiota to health and
      disease. Dysbiosis of the microbial communities colonizing the human intestinal
      tract has been described for a variety of chronic diseases, such as inflammatory
      bowel disease, obesity and asthma. In particular, reduction of several so-called
      probiotic species including Lactobacilli and Bifidobacteria that are generally
      considered to be beneficial, as well as an outgrowth of potentially pathogenic
      bacteria is often reported. Thus a tempting therapeutic approach is to shape the
      constituents of the microbiota in an attempt to restore the microbial balance
      towards the growth of 'health-promoting' bacterial species. A twist to this
      scenario is the recent discovery that the respiratory tract also harbors a
      microbiota under steady-state conditions. Investigators have shown that the
      microbial composition of the airway flora is different between healthy lungs and
      those with chronic lung diseases, such as asthma, chronic obstructive pulmonary
      disease as well as cystic fibrosis. This is an emerging field, and thus far there
      is very limited data showing a direct contribution of the airway microbiota to
      the onset and progression of disease. However, should future studies provide such
      evidence, the airway microbiota might soon join the intestinal microbiota as a
      target for therapeutic intervention. In this review, we highlight the major
      advances that have been made describing the microbiota in chronic lung disease
      and discuss current and future approaches concerning manipulation of the
      microbiota for the treatment and prevention of disease.

PMID- 23969227
TI  - Quantitative proteomic profiling of tumor cell response to telomere dysfunction
      using isotope-coded protein labeling (ICPL) reveals interaction network of
      candidate senescence markers.
AB  - Telomerase inhibition causes progressive telomere shortening and cellular
      senescence, which constitutes a universal barrier to tumor growth and therefore
      an attractive target for tumor therapy. To expand our previous studies, we
      investigated the global effects of telomere dysfunction on the proteome of tumor
      cells in order to find novel senescence biomarkers. Telomerase-deficient HCT-116
      cell clones were analyzed by a quantitative proteomic approach using isotope
      coded protein labeling (ICPL) and nanoflow-HPLC-MS/MS. Stringent reduction of the
      extensive proteomic data from this tumor cell model revealed a list of 59 markers
      including proteins identified in our former studies and a number of novel
      proteins involved in tumorigenesis and metastasis such as SFN, S100A4, ANXA2, and
      LGALS1. A loss of the chromatin protein HMGB2 was demonstrated not only in
      various telomerase-inhibited clones of different tumor cell lines, but also in
      normal human fibroblasts undergoing replicative senescence and in aging
      telomerase knockout mice. Impressively, a coherent and dense network of protein
      protein interactions for the bulk of the markers and their implementation in
      signaling pathways involving key regulators for tumorigenesis were revealed.
      These results have an impact on the understanding of telomere- and senescence
      related signal transduction in tumor cells in consideration of the general lack
      of senescence markers. BIOLOGICAL SIGNIFICANCE: Induction of cellular senescence
      constitutes a potent concept for tumor therapy which interferes with
      immortalization and additional hallmarks of cancer. The application of a powerful
      quantitative proteomic approach using isotope-coded protein labeling to an
      approved model for senescence represented by telomerase inhibited tumor cells led
      to the identification of novel candidate biomarkers for telomere dysfunction and
      replicative senescence. Thereby, the identified markers not only fit in the
      context of the investigated processes with a relevance for additional hallmarks
      of cancer but are also involved in a strong interaction network and integrated in
      canonical pathways centered around key cancer-relevant proteins. These potential
      markers alone or in combination will significantly extend the view on telomere
      associated signal transduction in tumor cells and contribute to the field of
      cellular senescence and aging in consideration of the general lack of biomarkers
      in this regard.

PMID- 23969229
TI  - A review of the mechanism for poor placentation in early-onset preeclampsia: the
      role of autophagy in trophoblast invasion and vascular remodeling.
AB  - Shallow trophoblast invasion and impaired vascular remodeling of spiral arteries
      have been recognized in early-onset preeclampsia. Placentation and vascular
      remodeling are multistep processes, and hypoxia, placental oxidative stress,
      excessive or atypical maternal immune response to trophoblasts, exaggerated
      inflammation, and increased production of anti-angiogenic factors such as the
      soluble form of the vascular endothelial growth factor (VEGF) receptor (sFlt-1)
      and soluble endoglin (sENG) may play a role in poor placentation in preeclampsia.
      Recent findings suggest that autophagy plays an important role in extravillous
      trophoblast (EVT) invasion and vascular remodeling under hypoxia, and sENG
      inhibits EVT invasion and vascular remodeling by the inhibition of autophagy
      under hypoxic conditions. In this review, we discuss the relationship between
      inadequate autophagy and poor placentation in preeclampsia. 

PMID- 23969228
TI  - Identification of mitochondrial dysfunction in Hutchinson-Gilford progeria
      syndrome through use of stable isotope labeling with amino acids in cell culture.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a rare segmental premature aging
      disorder that recapitulates some biological and physical aspects of physiological
      aging. The disease is caused by a sporadic dominant mutation in the LMNA gene
      that leads to the expression of progerin, a mutant form of lamin A that lacks 50
      amino acids and retains a toxic farnesyl modification in its carboxy-terminus.
      However, the mechanisms underlying cellular damage and senescence and accelerated
      aging in HGPS are incompletely understood. Here, we analyzed fibroblasts from
      healthy subjects and HGPS patients using SILAC (stable isotope labeling with
      amino acids in cell culture). We found in HGPS cells a marked downregulation of
      mitochondrial oxidative phosphorylation proteins accompanied by mitochondrial
      dysfunction, a process thought to provoke broad organ decline during normal
      aging. We also found mitochondrial dysfunction in fibroblasts from adult
      progeroid mice expressing progerin (Lmna(G609G/G609G) knock-in mice) or prelamin
      A (Zmpste24-null mice). Analysis of tissues from these mouse models revealed that
      the damaging effect of these proteins on mitochondrial function is time- and dose
      dependent. Mitochondrial alterations were not observed in the brain, a tissue
      with extremely low progerin expression that seems to be unaffected in HGPS.
      Remarkably, mitochondrial function was restored in progeroid mouse fibroblasts
      treated with the isoprenylation inhibitors FTI-277 or pravastatin plus
      zoledronate, which are being tested in HGPS clinical trials. Our results suggest
      that mitochondrial dysfunction contributes to premature organ decline and aging
      in HGPS. Beyond its effects on progeria, prelamin A and progerin may also
      contribute to mitochondrial dysfunction and organ damage during normal aging,
      since these proteins are expressed in cells and tissues from non-HGPS
      individuals, most prominently at advanced ages. BIOLOGICAL SIGNIFICANCE:
      Mutations in LMNA or defective processing of prelamin A causes premature aging
      disorders, including Hutchinson-Gilford progeria syndrome (HGPS). Most HGPS
      patients carry in heterozygosis a de-novo point mutation (c.1824C>T: GGC>GGT;
      p.G608G) which causes the expression of the lamin A mutant protein called
      progerin. Despite the importance of progerin and prelamin A in accelerated aging,
      the underlying molecular mechanisms remain largely unknown. To tackle this
      question, we compared the proteome of skin-derived dermal fibroblast from HGPS
      patients and age-matched controls using quantitative stable isotope labeling with
      amino acids in cell culture (SILAC). Our results show a pronounced down
      regulation of several components of the mitochondrial ATPase complex accompanied
      by up-regulation of some glycolytic enzymes. Accordingly, functional studies
      demonstrated mitochondrial dysfunction in HGPS fibroblasts. Moreover, our
      expression and functional studies using cellular and animal models confirmed that
      mitochondrial dysfunction is a feature of progeria which develops in a time- and
      dose-dependent manner. Finally, we demonstrate improved mitochondrial function in
      progeroid mouse cells treated with a combination of statins and
      aminobisphosphonates, two drugs that are being evaluated in ongoing HGPS clinical
      trials. Although further studies are needed to unravel the mechanisms through
      which progerin and prelamin A provoke mitochondrial abnormalities, our findings
      may pave the way to improved treatments of HGPS. These studies may also improve
      our knowledge of the mechanisms leading to mitochondrial dysfunction during
      normal aging, since both progerin and prelamin A have been found to accumulate
      during normal aging.

PMID- 23969230
TI  - Saikosaponin A of Bupleurum chinense (Chaihu) elevates bone morphogenetic protein
      4 (BMP-4) during hepatic stellate cell activation.
AB  - BACKGROUND: Saikosaponin a (SSa) is a compound extracted from a Chinese herb
      which has been widely used in treating liver diseases such as liver fibrosis.
      However, the mechanism of SSa in treatment of liver fibrosis still remain
      unclear. Our previous study demonstrated that BMP4 stimulated the expression of
      smooth muscle alpha actin (alpha-SMA) in the liver. Therefore, the current study
      investigates the effect of SSa on BMP4 expression during hepatic stellate cell
      activation in a human hepatic stellate cell line. METHODS: LX-2 cells were
      cultured in DMEM/F12 with fetal bovine serum and treated with SSa in different
      times and concentrations. The expression of BMP4 was examined by both RT-PCR and
      western blot analysis. WST-1 proliferation reagent was used to evaluate cell
      proliferation. alpha-SMA and Bax protein expression was determined by western
      blot analysis. RESULTS: Both mRNA and protein levels of BMP-4 were significantly
      inhibited in LX-2 cells after 5 MUM SSa treatment. SSa significantly inhibited LX
      2 proliferation at the concentration of 5MUM while BMP-4 had no effect on LX-2
      proliferation. BMP-4 increased alpha-SMA expression in LX-2 while SSa reduced
      alpha-SMA expression. In addition SSa could neutralize the effect of BMP-4 on
      alpha-SMA expression. SSd also inhibited BMP4 expression but not NG. Bax protein
      expression was induced in these cells by 5 MUM SSa. CONCLUSION: SSa could down
      regulate BMP-4 expression and inhibit hepatic stellate cell activation.
      Therefore, SSa could be used for treatment of liver disease with elevated BMP-4
      expression.

PMID- 23969231
TI  - The one-two punch: combination treatment in chronic myeloid leukemia.
AB  - Despite the success of tyrosine kinase inhibitor (TKI) therapy in patients with
      chronic myeloid leukemia (CML), minimal residual disease persists, requiring
      indefinite treatment. Accumulated evidence has shown that leukemic stem cells
      (LSCs) in the bone marrow can survive TKI treatment via downstream BCR-ABL1
      independent signaling pathways that are activated by soluble growth factors and
      interactions with the extracellular matrix in the bone marrow microenvironment.
      Research efforts have therefore turned to the identification and development of
      agents that target LSCs, and together with TKIs, have the potential to eradicate
      CML. A number of such agents are now under clinical investigation, and others are
      soon to enter early-phase studies. This review examines the pathways, molecular
      targets, and potential new therapeutics that, with TKIs, may provide an effective
      "one-two punch" to cure CML.

PMID- 23969232
TI  - Negative reward expectations in Borderline Personality Disorder patients:
      neurophysiological evidence.
AB  - Borderline Personality Disorder (BPD) patients present profound disturbances in
      affect regulation and impulse control which could reflect a dysfunction in reward
      related processes. The current study investigated these processes in a sample of
      18 BPD patients and 18 matched healthy controls, using an event-related brain
      potentials methodology. Results revealed a reduction in the amplitude of the
      Feedback-Related Negativity of BPD patients, which is a neurophysiological index
      of the impact of negative feedback in reward-related tasks. This reduction, in
      the effect of negative feedback in BPD patients, was accompanied by a different
      behavioral pattern of risk choice compared to healthy participants. These
      findings confirm a dysfunctional reward system in BDP patients, which might
      compromise their capacity to build positive expectations of future rewards and
      decision making. 

PMID- 23969233
TI  - Chemical and thermochemical aspects of the ozonolysis of ethyl oleate:
      decomposition enthalpy of ethyl oleate ozonide.
AB  - Neat ethyl oleate was ozonized in a bubble reactor and the progress of the
      ozonolysis was followed by infrared (FT-IR) spectroscopy and by the differential
      scanning calorimetry (DSC). The ozonolysis was conducted till a molar ratio
      O3/C=C~1 when the exothermal reaction spontaneously went to completion. A
      specific thermochemical calculation on ethyl oleate ozonation has been made to
      determine the theoretical heat of the ozonization reaction using the group
      increment approach. A linear relationship was found both in the integrated
      absorptivity of the ozonide infrared band at 1110 cm(-1) and the ozonolysis time
      as well as the thermal decomposition enthalpy of the ozonides and peroxides
      formed as a result of the ozonation. The DSC decomposition temperature of
      ozonated ethyl oleate occurs with an exothermal peak at about 150-155  degrees C
      with a decomposition enthalpy of 243.0 kJ/mol at molar ratio O3/C=C~1. It is
      shown that the decomposition enthalpy of ozonized ethyl oleate is a constant
      value (~243 kJ/mol) at any stage of the O3/C=C once an adequate normalization of
      the decomposition enthalpy for the amount of the adsorbed ozone is taken into
      consideration. The decomposition enthalpy of ozonized ethyl oleate was also
      calculated using a simplified thermochemical model, obtaining a result in
      reasonable agreement with the experimental value.

PMID- 23969234
TI  - Environmental enrichment rescues DYRK1A activity and hippocampal adult
      neurogenesis in TgDyrk1A.
AB  - Hippocampal adult neurogenesis disruptions have been suggested as one of the
      neuronal plasticity mechanisms underlying learning and memory impairment in Down
      syndrome (DS). However, it remains unknown whether specific candidate genes are
      implicated in these phenotypes in the multifactorial context of DS. Here we
      report that transgenic mice (TgDyrk1A) with overdosage of Dyrk1A, a DS candidate
      gene, show important alterations in adult neurogenesis including reduced cell
      proliferation rate, altered cell cycle progression and reduced cell cycle exit
      leading to premature migration, differentiation and reduced survival of newly
      born cells. In addition, less proportion of newborn hippocampal TgDyrk1A neurons
      are activated upon learning, suggesting reduced integration in learning circuits.
      Some of these alterations were DYRK1A kinase-dependent since we could rescue
      those using a DYRK1A inhibitor, epigallocatechin-3-gallate. Environmental
      enrichment also normalized DYRK1A kinase overdosage in the hippocampus, and
      rescued adult neurogenesis alterations in TgDyrk1A mice. We conclude that Dyrk1A
      is a good candidate to explain neuronal plasticity deficits in DS and that
      normalizing the excess of DYRK1A kinase activity either pharmacologically or
      using environmental stimulation can correct adult neurogenesis defects in DS.

PMID- 23969235
TI  - Posttranscriptional regulation of SOD1 gene expression under oxidative stress:
      Potential role of ELAV proteins in sporadic ALS.
AB  - Increased levels of SOD1 mRNA have been observed in sporadic ALS patients (SALS)
      compared to controls. Hence, the understanding of the mechanisms by which SOD1
      gene expression is modulated may shed new light on SOD1 involvement in ALS. Of
      interest, some adenine/uracil-rich elements (AREs) in SOD1 3'-untranslated region
      have been identified. These sequences represent the docking sites for several RNA
      binding proteins such as ELAV proteins (ELAVs), positive regulators of gene
      expression. We first investigated in SH-SY5Y cells whether SOD1 mRNA represents a
      target of ELAVs. Results from RNA Electrophoretic Mobility Shift and RNA
      immunoprecipitation assays showed a molecular interaction between ELAVs and SOD1
      mRNA. We also observed that the treatment with H2O2 induced a significant
      increase of the amount of SOD1 mRNA bound by ELAVs and an up-regulation of SOD1
      protein levels. We found a specific increase in ELAV/HuR phosphorylation,
      suggesting activation of this protein, in peripheral blood mononuclear cells from
      SALS patients compared to controls. Finally, we found increased levels of ELAV
      proteins in the motor cortex and spinal cord from SALS patients compared to
      controls, in parallel with SOD1 up-regulation in the same areas. This study
      suggests, for the first time, that ELAVs are involved in the regulation of SOD1
      gene expression at post-transcriptional level and that these proteins are more
      activated in ALS pathology. The link between ELAVs and SOD1 may open novel
      perspectives for ALS research, paving the way for new therapeutic options.

PMID- 23969236
TI  - Genetic ablation of phospholipase C delta 1 increases survival in SOD1(G93A)
      mice.
AB  - Amyotrophic Lateral Sclerosis (ALS) is a devastating progressive
      neurodegenerative disease, resulting in selective motor neuron degeneration and
      paralysis. Patients die approximately 3-5 years after diagnosis. Disease
      pathophysiology is multifactorial, including excitotoxicity, but is not yet fully
      understood. Genetic analysis has proven fruitful in the past to further
      understand genes modulating the disease and increase knowledge of disease
      mechanisms. Here, we revisit a previously performed microsatellite analysis in
      ALS and focus on another hit, PLCD1, encoding phospholipase C delta 1
      (PLCdelta1), to investigate its role in ALS. PLCdelta1 may contribute to
      excitotoxicity as it increases inositol 1,4,5-trisphosphate (IP3) formation,
      which releases calcium from the endoplasmic reticulum through IP3 receptors. We
      find that expression of PLCdelta1 is increased in ALS mouse spinal cord and in
      neurons from ALS mice. Furthermore, genetic ablation of this protein in ALS mice
      significantly increases survival, but does not affect astrogliosis, microgliosis,
      aggregation or the amount of motor neurons at end stage compared to ALS mice with
      PLCdelta1. Interestingly, genetic ablation of PLCdelta1 prevents nuclear
      shrinkage of motor neurons in ALS mice at end stage. These results indicate that
      PLCD1 contributes to ALS and that PLCdelta1 may be a new target for future
      studies.

PMID- 23969237
TI  - DJ-1 facilitates the interaction between STAT1 and its phosphatase, SHP-1, in
      brain microglia and astrocytes: A novel anti-inflammatory function of DJ-1.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative movement disorder
      caused by the death of dopaminergic neurons in the substantia nigra. Importantly,
      altered astrocyte and microglial functions could contribute to neuronal death in
      PD. In this study, we demonstrate a novel mechanism by which DJ-1 (PARK7), an
      early onset autosomal-recessive PD gene, negatively regulates inflammatory
      responses of astrocytes and microglia by facilitating the interaction between
      STAT1 and its phosphatase, SHP-1 (Src-homology 2-domain containing protein
      tyrosine phosphatase-1). Astrocytes and microglia cultured from DJ-1-knockout
      (KO) mice exhibited increased expression of inflammatory mediators and
      phosphorylation levels of STAT1 (p-STAT1) in response to interferon-gamma (IFN
      gamma) compared to cells from wild-type (WT) mice. DJ-1 deficiency also
      attenuated IFN-gamma-induced interactions of SHP-1 with p-STAT1 and STAT1,
      measured 1 and 12h after IFN-gamma treatment, respectively. Subsequent
      experiments showed that DJ-1 directly interacts with SHP-1, p-STAT1, and STAT1.
      Notably, DJ-1 bound to SHP-1 independently of IFN-gamma, whereas the interactions
      of DJ-1 with p-STAT1 and STAT1 were dependent on IFN-gamma. Similar results were
      obtained in brain slice cultures, where IFN-gamma induced much stronger STAT1
      phosphorylation and inflammatory responses in KO slices than in WT slices.
      Moreover, IFN-gamma treatment induced neuronal damage in KO slices. Collectively,
      these findings suggest that DJ-1 may function as a scaffold protein that
      facilitates SHP-1 interactions with p-STAT1 and STAT1, thereby preventing
      extensive and prolonged STAT1 activation. Thus, the loss of DJ-1 function may
      increase the risk of PD by enhancing brain inflammation.

PMID- 23969240
TI  - [Facioscapulohumeral muscular dystrophy type 2].
AB  - INTRODUCTION: In recent years, the advances of knowledge in clinical, genetic and
      epigenetic features of facioscapulohumeral muscular dystrophy (FSHD) allowed the
      identification of two forms of FSHD, the classical autosomal dominant FSHD type
      1, and FSHD type 2 characterized by an identical clinical phenotype but
      associated with a different (epi)genetic defect. STATE OF THE ART: In the large
      majority of FSHD1 patients, the identification of D4Z4 pathogenic contraction on
      a permissive chromosome 4 is sufficient for diagnosis, while FSHD2 diagnosis is
      complicated by the fact that the genetic defect associated with this disease is
      not known yet and a complete D4Z4 genotype and a D4Z4 specific methylation test
      are required. Indeed, FSHD2 patients display a non-contracted D4Z4 allele on
      chromosomes 4, at least one permissive chromosome 4QA and a profound
      hypomethylation of both chromosomes 4 and 10. A common pathophysiological pathway
      has been hypothesized for FSHD1 and FSHD2 in order to explain the identical
      clinical phenotype and the highly similar epigenetic changes found in patients
      affected by these diseases. According to this hypothesis, chromatin relaxation -
      due to pathogenic D4Z4 contraction in FSHD1 patients, and to important
      hypomethylation of this locus in FSHD2 patients - would allow the last D4Z4 unit
      to encode for a toxic DUX4 transcript. This transcript would be stable only when
      encoded from a permissive chromosome 4 carrying a polyadenylation signal
      immediately distal to the last D4Z4 unit on chromosome 4. PERSPECTIVES: Since, to
      express clinical phenotype, FSHD2 patients have to carry both 4QA chromosome and
      hypomethylated D4Z4 on chromosomes 4 and 10, digenic transmission has been
      hypothesized for this disease. The identification of the gene(s) and the exact
      epigenetic pathway underlining this disease will be mandatory to increase the
      rate of diagnosis for FSHD2 patients and to confirm the hypothesis of a common
      FSHD1 and FSHD2 pathophysiological pathway involving DUX4 gene. CONCLUSIONS: The
      identification, among patients carrying a FSHD phenotype, of FSHD2, a new disease
      with distinct (epi)genetic features but having a common pathophysiological
      pathway with FSHD1, suggests the possibility of developping new therapeutic
      strategies suitable for both diseases.

PMID- 23969241
TI  - [IMRT and head and neck tumors: does differential fractionation have a role?].
AB  - For head and neck cancer, intensity-modulated radiation therapy (IMRT) provides
      benefits in terms of coverage of the target tumour volume and reduction of the
      dose to organs at risk. Altered fractionation called SMART (simultaneous
      modulated accelerated radiation therapy) or SIB (simultaneous integrated boost),
      equivalent to the "concomitant boost" of conventional techniques, provides
      additional theoretical gain in the therapeutic index and simplifies the practical
      implementation of the treatment. The impact on tumour control and acute and late
      toxicities is encouraging but needs to be confirmed by prospective clinical
      studies with sufficient follow-up. A lot of different protocols have been tested
      without really bringing out a "gold standard". However, the current results tend
      to suggest a SIB/SMART-IMRT moderately accelerated without combined chemotherapy
      for limited stages (I and II), and SIB-IMRT slightly accelerated with induction
      and/or concomitant chemotherapy for more advanced stages (III and IV). 

PMID- 23969242
TI  - [Pelvic lymph nodes imaging].
AB  - Detecting metastatic pelvic lymph nodes is essential during the survey of a
      pelvic carcinoma. In routine clinical practice, CT scan is commonly used.
      However, its accuracy is quite low for small size lymph nodes. Diffusion-weighted
      imaging could be in the near future an efficient modality. 

PMID- 23969243
TI  - [Obesity and radiation: technical difficulties, toxicity and efficacy].
AB  - The number of obese patients has increased in France over the last two decades,
      which has had an impact on the incidence of numerous types of cancer. The
      treatment of cancer by radiotherapy is impacted by obesity as a result of the
      physical, technical and dosimetric constraints, the acute and late toxicity,
      local control and the survival of patients. 

PMID- 23969238
TI  - Role of calpains in the injury-induced dysfunction and degeneration of the
      mammalian axon.
AB  - Axonal injury and degeneration, whether primary or secondary, contribute to the
      morbidity and mortality seen in many acquired and inherited central nervous
      system (CNS) and peripheral nervous system (PNS) disorders, such as traumatic
      brain injury, spinal cord injury, cerebral ischemia, neurodegenerative diseases,
      and peripheral neuropathies. The calpain family of proteases has been
      mechanistically linked to the dysfunction and degeneration of axons. While the
      direct mechanisms by which transection, mechanical strain, ischemia, or
      complement activation trigger intra-axonal calpain activity are likely different,
      the downstream effects of unregulated calpain activity may be similar in
      seemingly disparate diseases. In this review, a brief examination of axonal
      structure is followed by a focused overview of the calpain family. Finally, the
      mechanisms by which calpains may disrupt the axonal cytoskeleton, transport, and
      specialized domains (axon initial segment, nodes, and terminals) are discussed.

PMID- 23969239
TI  - Loss of corticostriatal and thalamostriatal synaptic terminals precedes striatal
      projection neuron pathology in heterozygous Q140 Huntington's disease mice.
AB  - Motor slowing, forebrain white matter loss, and striatal shrinkage have been
      reported in premanifest Huntington's disease (HD) prior to overt striatal neuron
      loss. We carried out detailed LM and EM studies in a genetically precise HD
      mimic, heterozygous Q140 HD knock-in mice, to examine the possibility that loss
      of corticostriatal and thalamostriatal terminals prior to striatal neuron loss
      underlies these premanifest HD abnormalities. In our studies, we used VGLUT1 and
      VGLUT2 immunolabeling to detect corticostriatal and thalamostriatal
      (respectively) terminals in dorsolateral (motor) striatum over the first year of
      life, prior to striatal projection neuron pathology. VGLUT1+ axospinous
      corticostriatal terminals represented about 55% of all excitatory terminals in
      striatum, and VGLUT2+ axospinous thalamostriatal terminals represented about 35%,
      with VGLUT1+ and VGLUT2+ axodendritic terminals accounting for the remainder. In
      Q140 mice, a significant 40% shortfall in VGLUT2+ axodendritic thalamostriatal
      terminals and a 20% shortfall in axospinous thalamostriatal terminals were
      already observed at 1 month of age, but VGLUT1+ terminals were normal in
      abundance. The 20% deficiency in VGLUT2+ thalamostriatal axospinous terminals
      persisted at 4 and 12 months in Q140 mice, and an additional 30% loss of VGLUT1+
      corticostriatal terminals was observed at 12 months. The early and persistent
      deficiency in thalamostriatal axospinous terminals in Q140 mice may reflect a
      development defect, and the impoverishment of this excitatory drive to striatum
      may help explain early motor defects in Q140 mice and in premanifest HD. The loss
      of corticostriatal terminals at 1 year in Q140 mice is consistent with prior
      evidence from other mouse models of corticostriatal disconnection early during
      progression, and can explain both the measurable bradykinesia and striatal white
      matter loss in late premanifest HD.

PMID- 23969244
TI  - [Organization and prerequisites for the delegation of dosimetry tasks].
AB  - The planning of irradiation treatments is a task of medical physics, based on the
      appropriate calculations of a dose distribution from radiation beams, virtually
      set up on a simulation software. This task is at the centre of the chain of
      treatment preparation: between the contouring phase and the objective definition,
      which are specialties of the radiation oncologist, and the joint validation of
      the treatment plan by the physician and the physicist. Historically, this task
      has been performed by the medical physicist, but can be delegated to other
      professionals, especially radiation technologists. The evolution of the
      techniques and procedures tends to a specialization of the skilled workers toward
      this new work of dosimetry specialist or treatment planning technician. In this
      paper, the training, relational and organizational aspects will be described to
      explain how the delegation of the tasks, in the context of treatment plan
      preparation between professionals can be set up with the highest level of quality
      and security for the patient treatment and with the respect of legal obligations
      and requirements of each profession. 

PMID- 23969245
TI  - [Hypofractionation and radiotherapy: "the eternal return"].
AB  - Hypofractionation is not a new idea in radiotherapy. The use of a few high-dose
      fractions has been proposed by some pioneers of our specialty in the early years
      of the 20th century. Hypofractionation then reappeared several times in the next
      decades, based on successive radiobiological concepts, a number of them having
      been shown to be wrong. The nominal single dose (NSD), for example, so
      fashionable in the 1970's, dramatically underestimated the late toxicity of the
      high-dose fractions. Consequently, the NSD was directly responsible for a
      significant increase of the incidence and of the severity of late complications
      in large cohorts of patients. The linear-quadratic model (LQ) unequivocally
      improved our understanding of fractionation sensitivity, but one has to keep in
      mind its limitations, both in the areas of low and high doses per fraction. For
      more than a decade, prostate cancer has been the subject of fierce discussions
      about its sensitivity to fractionation. A number of studies have suggested an
      unusually low (for a malignant tumor) alpha/beta ratio. However, the available
      data do not allow a precise evaluation of this ratio; "very low" (1.5 Gy), with
      an advantage of hypofractionation in terms of local control? Or simply "low" (3-4
      Gy), only allowing a reduction of the total number of fractions (with a dose
      adequately reduced)? While waiting for complementary data, it is advised to
      remain very careful when modifying the classical schemes towards
      hypofractionation. 

PMID- 23969246
TI  - [Bladder cancer radiotherapy margins].
AB  - Radical cystectomy is the gold standard treatment of invasive bladder carcinoma,
      but conservative treatment is a serious option for selected patients. It
      comprises a transurethral resection, as complete as possible, before a radiation
      therapy of the whole bladder and pelvis, with a concomitant chemotherapy. Bladder
      wall movements during the treatment course lead to the use of wide margins to
      cover the clinical target volume. Planning target volume margins must be
      anisotropic to correspond to the mobility of each bladder zone: 10mm in the
      inferior portion, 15 mm in lateral directions, and 20 to 25 mm in anterior and
      superior directions. The development of image-guided radiotherapy and adaptative
      radiotherapy should lead to a reduction of these margins. Besides, partial
      bladder radiotherapy is showing encouraging results, by reducing the clinical
      target volume in well-selected patients.

PMID- 23969247
TI  - Lipidomics as a principal tool for advancing biomedical research.
AB  - Lipidomics, which targets at the construction of a comprehensive map of lipidome
      comprising the entire lipid pool within a cell or tissue, is currently emerging
      as an independent discipline at the interface of lipid biology, technology and
      medicine. The diversity and complexity of the biological lipidomes call for
      technical innovation and improvement to meet the needs of various biomedical
      studies. The recent wave of expansion in the field of lipidomic research is
      mainly attributed to advances in analytical technologies, in particular, the
      development of new mass spectrometric and chromatographic tools for the
      characterization and quantification of the wide array of diverse lipid species in
      the cellular lipidome. Here, we review some of the key technical advances in
      lipidome analysis and put forth the applications of lipidomics in addressing the
      biological roles of lipids in numerous disease models including the metabolic
      syndrome, neurodegenerative diseases and infectious diseases, as well as the
      increasing urgency to construct the lipidome inventory for various
      mammalian/organism models useful for biomedical research. 

PMID- 23969248
TI  - Rb protein is essential to the senescence-associated heterochromatic foci
      formation induced by HMGA2 in primary WI38 cells.
AB  - Cellular senescence is an irreversible form of cell cycle arrest that provides a
      barrier to neoplastic transformation. The integrity of the Rb (Retinoblastoma)
      pathway is necessary for the formation of the senescence-associated
      heterochromatin foci (SAHF) that offers a molecular basis for the stability of
      the senescent state. Surprisingly, although high mobility group A2 protein
      (HMGA2) can promote tumorigenesis and inhibit Rb function in tumor cells, high
      level expression of HMGA2 is sufficient to induce SAHF formation in primary
      cells. It therefore becomes significant to determine whether Rb protein is
      necessary in HMGA2-induced SAHF formation. In this study, we established the
      cellular senescence and SAHF assembly WI38 cell model by ectopic expression of
      HMGA2, in which typical senescent markers were seen, including notable
      upregulation of p53, p21 and p16, and elevated SA-beta-galactosidase staining
      together with downregulation of E2F target genes. We then showed that the Rb
      pathway inhibitor E7 protein was able to partly abolish the ability of SAHF
      formation after HMGA2 expression in WI38 cells, indicating that Rb is a crucial
      factor for HMGA2-induced SAHF formation. However, Rb depletion did not completely
      rescue the cell growth arrest induced by HMGA2, suggesting that Rb is not an
      exclusive pathway for HMGA2-induced senescence in WI38 cells. 

PMID- 23969249
TI  - Evolutionary and functional analysis of the key pluripotency factor Oct4 and its
      family proteins.
AB  - Oct4 is one of the key pluripotent factors essential for embryonic stem cells and
      induced pluripotent stem (iPS) cells. Oct4 belongs to the POU domain family,
      which contains multiples genes with various important functions. Although the
      function of Oct4 has been extensively studied, detailed comparison of Oct4 with
      other POU family genes and their evolutionary analysis are still lacking. Here,
      we systematically identified POU family genes from lower to higher animal
      species. We observed an expansion of POU family genes in vertebrates, with an
      additional increment in mammalian genomes. We analyzed the phylogenetic
      relationship, tissue specific expression profiles and regulatory networks of POU
      family genes of the human genome, and predicted the putative binding microRNAs of
      human POU family genes. These results provide the first comprehensive
      evolutionary and comparative analysis of POU family genes, which will help to
      better understand the relationships among POU family genes and shed light on
      their future functional studies. 

PMID- 23969250
TI  - Alteration of terminal heterochromatin and chromosome rearrangements in
      derivatives of wheat-rye hybrids.
AB  - Wheat-rye addition and substitution lines and their self progenies revealed
      variations in telomeric heterochromatin and centromeres. Furthermore, a
      mitotically unstable dicentric chromosome and stable multicentric chromosomes
      were observed in the progeny of a Chinese Spring-Imperial rye 3R addition line.
      An unstable multicentric chromosome was found in the progeny of a 6R/6D
      substitution line. Drastic variation of terminal heterochromatin including
      movement and disappearance of terminal heterochromatin occurred in the progeny of
      wheat-rye addition line 3R, and the 5RS ditelosomic addition line. Highly stable
      minichromosomes were observed in the progeny of a monosomic 4R addition line, a
      ditelosomic 5RS addition line and a 6R/6D substitution line. Minichromosomes,
      with and without the FISH signals for telomeric DNA (TTTAGGG)n, derived from a
      monosomic 4R addition line are stable and transmissible to the next generation.
      The results indicated that centromeres and terminal heterochromatin can be
      profoundly altered in wheat-rye hybrid derivatives. 

PMID- 23969251
TI  - Functional analysis of autophagy genes via Agrobacterium-mediated transformation
      in the vascular Wilt fungus Verticillium dahliae.
AB  - Autophagy is a widely conserved intracellular process for degradation and
      recycling of proteins, organelles and cytoplasm in eukaryotic organisms and is
      now emerging as an important process in foliar infection by many plant pathogenic
      fungi. However, the role of autophagy in soil-borne fungal physiology and
      infection biology is poorly understood. Here, we report the establishment of an
      Agrobacterium tumefaciens-mediated transformation (ATMT) system and its
      application to investigate two autophagy genes, VdATG8 and VdATG12, by means of
      targeted gene replacement and complementation. Transformation of a cotton
      infecting Verticillium dahliae strain Vd8 with a novel binary vector pCOM led to
      the production of 384 geneticin-resistant transformants per 1 * 10(6) conidia. V.
      dahliae mutants lacking either VdATG8 or VdATG12 exhibited reduced conidiation
      and impaired aerial hyphae production. Disease development on Arabidopsis plants
      was slightly delayed when inoculated with VdATG8 or VdATG12 gene deletion
      mutants, compared with the wild-type and gene complemented strains. Surprisingly,
      in vitro inoculation with unimpaired roots revealed that the abilities of root
      invasion were not affected in gene deletion mutants. These results indicate that
      autophagy is necessary for aerial hyphae development and plant colonization but
      not for root infection in V. dahliae.

PMID- 23969252
TI  - Association of renin binding protein (RnBP) gene polymorphisms with essential
      hypertension in the Hani minority of southwestern China.

PMID- 23969253
TI  - Structural and expressional variation analyses of mitochondrial genomes reveal
      candidate transcripts for the S(V) cytoplasmic male sterility in wheat (Triticum
      aestivum L.).

PMID- 23969254
TI  - Genome-wide analysis of gene expression in stationary phase and genetic
      characterization of stationary-phase-dependent halocin gene expression in the
      haloarchaeon Haloferax mediterranei.

PMID- 23969255
TI  - Sidney Katz, MD: a new paradigm for chronic illness and long-term care.
AB  - Dr. Sidney Katz's legacy to the field of gerontology is internationally
      recognized as his success at developing standardized measures and processes,
      beginning with the activities of daily living index, for the functional
      assessment of older adults with chronic conditions necessitating long-term
      services and supports. That work served as the bedrock for his subsequent major
      accomplishments, which improved rehabilitation services through interdisciplinary
      team work and attention to the patient-family constellation; reformed the
      regulation of nursing homes, refocusing it on resident outcomes and quality of
      life; and promulgated the concept of active life expectancy as a new approach to
      measuring the quality of later life. Few other scholars and researchers in the
      history of the field of aging can claim one, much less multiple monumental
      contributions leading to major advances in the treatment of chronic illness and
      the quality of long-term care. 

PMID- 23969256
TI  - Improvements and decline in the physical functioning of Israeli older adults.
AB  - PURPOSE OF THE STUDY: The current study depicts improvement and decline in
      functioning among 3 population groups of Israeli older adults: Jews and veteran
      immigrants, former Soviet Union immigrants, and Arabs. METHODS: Using
      longitudinal data from 2005 and 2010 Survey of Health and Retirement (SHARE) in
      Israel (n = 982), we examined 4 functional changes in late life in mobility,
      movement, activities of daily living (ADL), and instrumental ADL, as a function
      of sociodemographic, health, and social variables RESULTS: The findings reveal
      that physical functioning among older adults can decline as well as improve over
      time. Older age, higher number of diseases and comorbidity, living with others
      (not the spouse) compared with living alone, receiving informal help and formal
      help with homemaking, and declined mental health and cognitive status predict
      deterioration in physical functioning. Also, Arab older adults are at higher risk
      of deterioration over time compared with Jewish older adults. IMPLICATIONS:
      Findings imply that noncompatible assistance to older adults may "save them the
      hassle" of doing things by themselves and thus, weakens a potential functional
      rehabilitation process. There is a need to guide not only professional personnel
      but also nonprofessional home care workers and family members on how to encourage
      and retain older adults' functions as much as possible in order to improve their
      quality of life. Another implication of investing in rehabilitation is that it
      might reduce the disability rate among older adults and thus save health
      expenditures on long-term care at the macrosocial level.

PMID- 23969257
TI  - Impact of medication aide use on skilled nursing facility quality.
AB  - PURPOSE OF THE STUDY: A number of states have begun to allow skilled nursing
      facilities to employ medication aides, who have less formal education than
      registered nurses (RNs) or licensed practical nurses (LPNs), to administer
      medications. If this results in fewer RNs or LPNs, quality degradation may occur.
      We evaluated the effect of regulations allowing for medication aides on
      subsequent medication aide use and the effect of changes in medication aide use
      on other nurse staffing, deficiencies, and Nursing Home Quality Initiative (NHQI)
      health outcome measures. DESIGN AND METHODS: Staffing levels and inspection
      deficiencies from the Online Survey and Certification and Reporting System and
      NHQI data from 2004 to 2010 for facilities from eight southeastern U.S. states
      are used in instrumental variables models with facility fixed effects. RESULTS:
      Facilities in states allowing for medication aide use increased medication aide
      use with no statistically significant reduction in RN or LPN use. Medication aide
      use decreased the probability that a facility received a deficiency citation for
      unnecessary drug use or having a medication error rate greater than or equal to
      5% and had no effect on deficiencies for significant or harmful medication
      errors. Increased medication aide use was associated with fewer pharmacy and
      total deficiency citations and decreased use of physical restraints; in contrast,
      more use of medication aides was associated with an increase in the percentage of
      residents needing help with activities of daily living and losing continence.
      IMPLICATIONS: This study provides support for state policies that allow skilled
      nursing facilities to use medication aides.

PMID- 23969258
TI  - Do productive activities reduce inflammation in later life? Multiple roles,
      frequency of activities, and C-reactive protein.
AB  - PURPOSE OF THE STUDY: The study investigates whether productive activities by
      older adults reduce bodily inflammation, as indicated by C-reactive protein
      (CRP), a biomeasure associated with the risk of cardiovascular diseases. DESIGN
      AND METHODS: The study uses a representative survey of adults aged 57-85 from the
      National Social Life, Health, and Aging Project (N = 1,790). Linear regression
      models were used to analyze the effects of multiple roles (employment,
      volunteering, attending meetings, and caregiving) and the frequency of activity
      within each role on log values of CRP concentration (mg/L) drawn from assayed
      blood samples. RESULTS: Number of roles for productive activities was associated
      with lower levels of CRP net of chronic conditions, lifestyle factors, and
      socioeconomic resources. When specific types of activity were examined,
      volunteering manifested the strongest association with lower levels of
      inflammation, particularly in the 70+ group. There was no evidence that frequent
      engagement in volunteer activity was associated with heightened inflammation.
      IMPLICATIONS: Productive activities-and frequent volunteering in particular-may
      protect individuals from inflammation that is associated with increased risk of
      hypertension and cardiovascular disease.

PMID- 23969260
TI  - A multifunctional pipette for localized drug administration to brain slices.
AB  - We have developed a superfusion method utilizing an open-volume microfluidic
      device for administration of pharmacologically active substances to selected
      areas in brain slices with high spatio-temporal resolution. The method consists
      of a hydrodynamically confined flow of the active chemical compound, which
      locally stimulates neurons in brain slices, applied in conjunction with
      electrophysiological recording techniques to analyze the response. The
      microfluidic device, which is a novel free-standing multifunctional pipette,
      allows diverse superfusion experiments, such as testing the effects of different
      concentrations of drugs or drug candidates on neurons in different cell layers
      with high positional accuracy, affecting only a small number of cells. We
      demonstrate herein the use of the method with electrophysiological recordings of
      pyramidal cells in hippocampal and prefrontal cortex brain slices from rats,
      determine the dependence of electric responses on the distance of the superfusion
      device from the recording site, document a multifold gain in solution exchange
      time as compared to whole slice perfusion, and show that the device is able to
      store and deliver up to four solutions in a series. Localized solution delivery
      by means of open-volume microfluidic technology also reduces reagent consumption
      and tissue culture expenses significantly, while allowing more data to be
      collected from a single tissue slice, thus reducing the number of laboratory
      animals to be sacrificed for a study. 

PMID- 23969261
TI  - Dual-energy CT: clinical application in differentiating an adrenal adenoma from a
      metastasis.
AB  - BACKGROUND: Application of dual-energy CT in characterization of adrenal nodules
      has not been well evaluated. PURPOSE: To evaluate the ability of dual-energy CT
      scan to differentiate an adrenal adenoma from a metastasis. MATERIAL AND METHODS:
      Fifty-five patients presenting 63 adrenal nodules underwent dual-energy CT scan
      at tube voltages of 80 kVp and 140 kVp. Mean attenuation values were measured for
      every nodule at 80/140 kVp and at 40/100 keV. Mean attenuation value changes
      between 140 kVp and 80 kVp (MAVC140-80kVp) and mean attenuation value changes
      between 100 keV and 40 keV (MAVC100-40keV) were calculated. RESULTS: Of the 63
      adrenal nodules available for analyses, 42 nodules were classified as adenoma (26
      lipid-rich and 16 lipid-poor) and 21 were classified as metastases. MAVC140-80kVp
      and MAVC100-40keV of all adenomas (including lipid-poor and lipid-rich) were
      significantly higher than metastases (P < 0.001). According to receiver-operating
      characteristic (ROC) curve analyses, areas under the ROC curve of MAVC140-80kVp
      and MAVC100-40keV for diagnosing adrenal adenomas were both of 0.964. When the
      cut-off points were set at 2.42 HU and 6.95 HU for MAVC140-80kVp and MAVC100
      40keV, the two parameters both had a sensitivity of 78.6% and a specificity of
      100% in adenoma diagnosis. CONCLUSION: Unique energy spectrum information
      provided by dual-energy CT scan displays a high capacity to distinguish adrenal
      adenoma from metastasis.

PMID- 23969262
TI  - BI-RADS(r) 3 lesions at contrast-enhanced breast MRI: is an initial short
      interval follow-up necessary?
AB  - BACKGROUND: Magnetic resonance imaging (MRI) BI-RADS(r) 3 lesions should have a
      very high probability of being benign. To prove benignity most institutions do
      follow-up MRI. PURPOSE: To evaluate the necessity of initial short-interval
      follow-up after 6 months as it is suggested for mammographic BI-RADS(r)3 lesions.
      MATERIAL AND METHODS: We analyzed 163 consecutive MRI-BI-RADS(r) 3 lesions on
      follow-up MRI: 75 masses (46%), 67 foci (41.1%), and 21 (12.9%) non-mass-like
      enhancing lesions (NMLE). RESULTS: During MRI follow-up (mean time, 563 days) 20%
      of the lesions disappeared, 23% decreased, 52% did not change, and 4.9% showed
      increase. All increasing lesions were biopsied (5 benign, 2 ductal carcinoma in
      situ, 1 invasive carcinoma). The rate of malignancy was 1.8%. All malignant
      lesions (1 mass, 1 focus, 1 NMLE) showed increase at initial follow-up after a
      mean interval of 190 days. CONCLUSION: In this study the malignancy rate of MRI
      BI-RADS(r) 3 lesions corresponded to mammographic BI-RADS(r) 3 lesions. Initial
      short-interval MRI should be suggested to identify malignant MRI-BI-RADS(r) 3
      lesions.

PMID- 23969263
TI  - Diffusion tensor imaging of the cervical spinal cord in healthy adult population:
      normative values and measurement reproducibility at 3T MRI.
AB  - BACKGROUND: Compared to diffusion tensor imaging (DTI) of the brain, there is a
      paucity of reports addressing the applicability of DTI in the evaluation of the
      spinal cord. Most normative data of cervical spinal cord DTI consist of
      relatively small and arbitrarily collected populations. Comprehensive normative
      data are necessary for clinical decision-making. PURPOSE: To establish normal
      values for cervical spinal cord DTI metrics with region of interest (ROI)- and
      fiber tractography (FT)-based measurements and to assess the reproducibility of
      both measurement methods. MATERIAL AND METHODS: Forty healthy adults underwent
      cervical spinal cord 3T MRI. Sagittal and axial conventional T2 sequences and DTI
      in the axial plane were performed. Whole cord fractional anisotropy (FA) and
      apparent diffusion coefficient (ADC) values were determined at different cervical
      levels from C2 to C7 using the ROI method. DTI metrics (FA, axial, and radial
      diffusivities based on eigenvalues lambda1, lambda2, and lambda3, and ADC) of the
      lateral and posterior funicles were measured at C3 level. FA and ADC of the whole
      cord and the lateral and posterior funicles were also measured using quantitative
      tractography. Intra- and inter-observer variation of the measurement methods were
      assessed. RESULTS: Whole cord FA values decreased and ADC values increased in the
      rostral to caudal direction from C2 to C7. Between the individual white matter
      funicles no statistically significant difference for FA or ADC values was found.
      Both axial diffusivity and radial diffusivity of both lateral funicles differed
      significantly from those of the posterior funicle. Neither gender nor age
      correlated with any of the DTI metrics. Intra-observer variation of the
      measurements for whole cord FA and ADC showed almost perfect agreement with both
      ROI and tractography-based measurements. There was more variation in measurements
      of individual columns. Inter-observer agreement varied from moderate to strong
      for whole cord FA and ADC. CONCLUSION: Both ROI- and FT-based measurements are
      applicable methods yielding reproducible results for cervical spinal cord DTI
      metrics. Normative values for both measurement methods are presented.

PMID- 23969264
TI  - The role of follow-up ultrasound and clinical parameters after abdominal MDCT in
      patients with multiple trauma.
AB  - BACKGROUND: Beside its value during the initial trauma work-up (focused
      assessment with sonography for trauma), ultrasound (US) is recommended for early
      follow-up examinations of the abdomen in multiple injured patients. However,
      multidetector CT (MDCT) has proven to reliably diagnose traumatic lesions of
      abdominal organs, to depict their extent, and to assess their clinical relevance.
      PURPOSE: To evaluate the diagnostic impact of follow-up US studies after MDCT of
      the abdomen and to identify possible clinical parameters indicating the need of a
      follow-up US. MATERIAL AND METHODS: During a 30-month period, patients with
      suspected multiple trauma were allocated. Patients with admission to the ICU, an
      initial abdominal MDCT scan, and an US follow-up examination after 6 and 24 h
      were included. Two patient cohorts were defined: patients with normal abdominal
      MDCT (group 1), patients with trauma-related pathologic abdominal MDCT (group 2).
      In all patients, parameters indicating alteration of vital functions or
      hemorrhage within the first 24 h were obtained by reviewing the medical charts.
      RESULTS: Forty-four of 193 patients were included: 24 were categorized in group 1
      (mean age, 41.1 years; range, 21-90 years), 20 in group 2 (mean age, 36.6 years;
      range, 16-71 years). In group 1, US did not provide new information compared to
      emergency MDCT. In group 2, there were no contradictory 6- and 24-h follow-up US
      findings. In patients with positive MDCT findings and alterations of clinical
      parameters, US did not detect progression of a previously diagnosed pathology or
      any late manifestation of such a lesion. In none of the patients with negative
      abdominal MDCT and pathological clinical parameters US indicated an abdominal
      injury. CONCLUSION: Routine US follow-up does not yield additional information
      after abdominal trauma. In patients with MDCT-proven organ lesions, follow-up
      MDCT should be considered if indicated by abnormal clinical and/or laboratory
      findings.

PMID- 23969265
TI  - Low-contrast-dose protocol in cardiac CT: 20% contrast dose reduction using 100
      kVp and high-tube-current-time setting in 256-slice CT.
AB  - BACKGROUND: The use of the smallest contrast dose is highly desirable in
      performing cardiac computed tomography (CT), especially for patients with
      cardiovascular diseases to prevent contrast-induced nephropathy. PURPOSE: To
      evaluate the feasibility of 20% reduced contrast dose protocol in cardiac CT
      using 100 kVp and high-tube-current-time product setting. MATERIAL AND METHODS:
      Fifty patients were scanned with our conventional 120 kVp protocol, and the other
      50 patients underwent scans using a tube voltage of 100 kVp, a high-tube-current
      time product, and a 20% reduced contrast dose. We evaluated estimated effective
      dose (ED), CT attenuation, image noise, and contrast-to-noise ratio (CNR) of the
      ascending aorta. We also evaluated CT attenuation of the coronary arteries. Two
      radiologists independently assessed image quality of coronary arteries. RESULTS:
      There was no significant difference in the ED between the 100 kVp and 120 kVp
      protocols (21.7 mSv +/- 1.6 vs. 21.8 mSv +/- 1.1, P=0.65). There was no
      significant difference in the CNR of the ascending aorta between the 100 kVp and
      120 kVp protocols (18.8 +/- 3.5 vs. 18.7 +/- 3.8, P=0.98). Mean CT attenuation of
      the coronary arteries of the 100 kVp protocols was significantly higher than that
      of 120 kVp protocols (P<0.05). There was no significant difference in the overall
      image quality of the coronary artery between the 100 kVp and 120 kVp protocols
      (3.7 +/- 0.4 vs. 3.7 +/- 0.5, P=0.65). CONCLUSION: For cardiac CT a voltage
      setting of 100 kVp and a high-tube-current-time product enable 20% reduction in
      the contrast dose without affecting the quality of coronary artery images
      compared with a 120 kVp and standard-contrast-dose CT protocol.

PMID- 23969266
TI  - Ultrasound findings of subacute thyroiditis: a single institution retrospective
      review.
AB  - BACKGROUND: High resolution ultrasonography features have also been described as
      having a useful supporting role in the diagnosis of subacute granulomatous
      thyroiditis (ST), and images are generally characterized by heterogeneous
      hypoechoic areas of the affected tissue with lack of flow on color Doppler US.
      PURPOSE: To determine the sonographic features of subacute granulomatous
      thyroiditis. MATERIAL AND METHODS: We reviewed the medical records of patients
      referred at the Endocrine and Metabolic Unit of our Institution between January
      2010 and December 2011. RESULTS: A total of 7520 patients were evaluated in our
      department between January 2010 and December 2011. Among them, 22 (0.3%) patients
      had a diagnosis of ST (19 women and 3 men, 45.4 +/- 9.7 year; range, 33-62
      years). Ultrasound examination showed bilateral ST in 64% of patients. Thyroid
      volume was 13.2 +/- 7.7 mL, without difference if ST was unilateral (13.2 +/- 7.1
      mL) or bilateral (13.9 +/- 8.3 mL). On grayscale US, heterogeneous diffusely or
      focally marked hypoechoic areas, like "lava flow", were found in all the lesions.
      CONCLUSION: Our data confirm the high sensitivity of US in the diagnosis of ST:
      diffuse hypoechoic and confluent areas with the characteristic features like
      "lava flow".

PMID- 23969267
TI  - Nutrition support clinicians: needed now more than ever.

PMID- 23969268
TI  - Improving patient outcomes through registered dietitian order writing.
AB  - Traditionally, registered dietitians (RD) have not had order writing privileges
      in most patient-care facilities and rely on physicians to implement their
      recommendations. Research has demonstrated that this model results in a high
      percentage of RD recommendations not being ordered. Timely nutrition
      interventions are important due to the prevalence of malnutrition in the hospital
      setting and when RD recommendations are implemented, important outcomes are
      improved. In addition, several studies have demonstrated that when RDs have order
      writing privileges, which allows more assurance that an intervention will occur
      and timely interventions, improved outcomes, such as improved nutrition status,
      better management of electrolytes and glycemic control, reaching goal calories
      sooner, reduction in inappropriate parenteral nutrition use, cost savings, and
      less error with electronic order entry. The process for implementation and
      outcomes of an RD order writing program at 1 large, urban, tertiary medical
      center is described. The program has been successful, but the implementation
      process required multiple years and ongoing monitoring through data collection to
      ensure success. RDs interested in order writing privileges must consider federal
      and state regulations, their individual scope of practice (relevant training and
      competency assessment), and how to obtain approval from the appropriate hospital
      governing committees. RDs who obtain order writing privileges must understand
      "with privilege comes responsibility" and should plan to conduct outcomes
      research to promote the value and acceptance of RD order writing by regulatory
      agencies at all levels and hospital leaders, for instance physicians and
      administrators. 

PMID- 23969269
TI  - Pressure to produce=pressure to reduce accident reporting?
AB  - Each year, more than 4 million U.S. workers are injured on the job - several
      thousand die (Bureau of Labor Statistics, 2008). Despite these staggering
      numbers, research suggests that they are gross underestimates of the true volume
      of workplace related illnesses and injuries due to accident under-reporting.
      Although accident under-reporting has been well-documented, less is known
      regarding why this occurs. The current study suggests that under-reporting may in
      part be due to high levels of perceived production pressure. Specifically, this
      study tested the hypotheses that production pressure would be related to more
      experienced accidents overall and more negative attitudes toward reporting
      accidents. Further, we expected that production pressure would exacerbate the
      under-reporting of accidents. Survey data were collected from a sample of 212
      copper mining workers located in the southwestern United States. The survey
      measured employee perceptions regarding production pressure, attitudes toward
      reporting accidents, perceived consequences of reporting accidents, and actual
      reporting behaviors (e.g., types and numbers of accidents experienced vs.
      reported). As predicted, the average number of experienced accidents per employee
      was significantly higher (M=2.84) than the number of reported accidents (M=.49).
      In addition, production pressure was related to more negative reporting
      attitudes. Individuals who had positive reporting attitudes were injured less
      frequently; however, when an incident occurred, they were more likely to report
      it. Finally, higher levels of production pressure were related to greater
      accident under-reporting. Additionally, employees who perceived high levels of
      production pressure not only experienced more accidents overall, they also
      reported fewer of them to the organization. Implications for occupational safety
      initiatives--particularly in the current economic climate--are discussed, as are
      methodological challenges of conducting research in this area.

PMID- 23969270
TI  - Distraction and driving: results from a case-control responsibility study of
      traffic crash injured drivers interviewed at the emergency room.
AB  - BACKGROUND: Use of cellular phones has been shown to be associated with crashes
      but many external distractions remain to be studied. OBJECTIVE: To assess the
      risk associated with diversion of attention due to unexpected events or secondary
      tasks at the wheel. DESIGN: Responsibility case-control study. SETTING: Adult
      emergency department of the Bordeaux University Hospital (France) from April 2010
      to August 2011. PARTICIPANTS: 955 injured drivers presenting as a result of motor
      vehicle crash. MAIN OUTCOME MEASURES: The main outcome variable was
      responsibility for the crash. Exposures were external distraction, alcohol use,
      psychotropic medicine use, and sleep deprivation. Potential confounders were
      sociodemographic and crash characteristics. RESULTS: Beyond classical risk factor
      found to be associated with responsibility, results showed that distracting
      events inside the vehicle (picking up an object), distraction due to driver
      activity (smoking) and distracting events occurring outside were associated with
      an increased probability of being at fault. These distraction-related factors
      accounted for 8% of injurious road crashes. LIMITATIONS: Retrospective
      responsibility self-assessment. CONCLUSIONS: Diverted attention may carry more
      risk than expected. Our results are supporting recent research efforts to detect
      periods of driving vulnerability related to inattention.

PMID- 23969271
TI  - Is road safety management linked to road safety performance?
AB  - This research aims to explore the relationship between road safety management and
      road safety performance at country level. For that purpose, an appropriate
      theoretical framework is selected, namely the 'SUNflower' pyramid, which
      describes road safety management systems in terms of a five-level hierarchy: (i)
      structure and culture, (ii) programmes and measures, (iii) 'intermediate'
      outcomes'--safety performance indicators (SPIs), (iv) final outcomes--fatalities
      and injuries, and (v) social costs. For each layer of the pyramid, a composite
      indicator is implemented, on the basis of data for 30 European countries.
      Especially as regards road safety management indicators, these are estimated on
      the basis of Categorical Principal Component Analysis upon the responses of a
      dedicated road safety management questionnaire, jointly created and dispatched by
      the ETSC/PIN group and the 'DaCoTA' research project. Then, quasi-Poisson models
      and Beta regression models are developed for linking road safety management
      indicators and other indicators (i.e. background characteristics, SPIs) with road
      safety performance. In this context, different indicators of road safety
      performance are explored: mortality and fatality rates, percentage reduction in
      fatalities over a given period, a composite indicator of road safety final
      outcomes, and a composite indicator of 'intermediate' outcomes (SPIs). The
      results of the analyses suggest that road safety management can be described on
      the basis of three composite indicators: "vision and strategy", "budget,
      evaluation and reporting", and "measurement of road user attitudes and
      behaviours". Moreover, no direct statistical relationship could be established
      between road safety management indicators and final outcomes. However, a
      statistical relationship was found between road safety management and
      'intermediate' outcomes, which were in turn found to affect 'final' outcomes,
      confirming the SUNflower approach on the consecutive effect of each layer.

PMID- 23969272
TI  - Appendiceal hamartoma resembling PHTS of soft tissue in a patient with Cowden
      syndrome.

PMID- 23969273
TI  - Histological evaluation of preoperative mediastinoscopy lymph node biopsies in
      non-small cell lung cancer.
AB  - INTRODUCTION: Despite the advent of PET scanning and endoscopic minimally
      invasive methods of sampling mediastinal lymph nodes, surgical assessment,
      particularly by mediastinoscopy, remains an important tool for staging non-small
      cell lung cancer. METHODS: We carried out a retrospective review of
      mediastinoscopic lymph node biopsies taken at The Royal Infirmary of Edinburgh
      between 1996 and 2006 and performed additional histological investigations on
      select cases. RESULTS: In total, 89/802 (11%) patients had a negative
      mediastinoscopy but final resection stage of N2/N3. Within this group, 41/89
      (46%) patients had positive resection lymph nodes in stations potentially
      accessible to biopsy at mediastinoscopy. Of these, 30 (34%) patients had had the
      metastatic station sampled at mediastinoscopy. Further histopathological
      examination (multiple levels and pancytokeratin immunohistochemistry) of these
      original biopsies detected micrometastases in two cases, one of which, in
      retrospect, had been missed on the original section at the time of reporting.
      Isolated tumour cells were detected by immunohistochemistry in another two cases.
      CONCLUSIONS: Routine examination of additional levels and immunohistochemical
      staining of mediastinal lymph nodes biopsies is not required and would not
      improve the overall negative predictive value of the procedure.

PMID- 23969274
TI  - Genomic profiling of plasma cell disorders in a clinical setting: integration of
      microarray and FISH, after CD138 selection of bone marrow.
AB  - AIM: To evaluate the role of whole genome comparative genomic hybridisation
      microarray (array-CGH) in detecting genomic imbalances as compared to
      conventional karyotype (GTG-analysis) or myeloma specific fluorescence in situ
      hybridisation (FISH) panel in a diagnostic setting for plasma cell dyscrasia
      (PCD). METHODS: A myeloma-specific interphase FISH (i-FISH) panel was carried out
      on CD138 PC-enriched bone marrow (BM) from 20 patients having BM biopsies for
      evaluation of PCD. Whole genome array-CGH was performed on reference (control)
      and neoplastic (test patient) genomic DNA extracted from CD138 PC-enriched BM and
      analysed. RESULTS: Comparison of techniques demonstrated a much higher detection
      rate of genomic imbalances using array-CGH. Genomic imbalances were detected in
      1, 19 and 20 patients using GTG-analysis, i-FISH and array-CGH, respectively.
      Genomic rearrangements were detected in one patient using GTG-analysis and seven
      patients using i-FISH, while none were detected using array-CGH. I-FISH was the
      most sensitive method for detecting gene rearrangements and GTG-analysis was the
      least sensitive method overall. All copy number aberrations observed in GTG
      analysis were detected using array-CGH and i-FISH. CONCLUSIONS: We show that
      array-CGH performed on CD138-enriched PCs significantly improves the detection of
      clinically relevant and possibly novel genomic abnormalities in PCD, and thus
      could be considered as a standard diagnostic technique in combination with IGH
      rearrangement i-FISH.

PMID- 23969275
TI  - Small intestinal mucosal xanthoma in a patient with CHILD syndrome.

PMID- 23969276
TI  - [Analysis of costs and cost-effectiveness of preferred GESIDA/National AIDS Plan
      regimens for initial antiretroviral therapy in human immunodeficiency virus
      infected adult patients in 2013].
AB  - INTRODUCTION: The GESIDA and National AIDS Plan panel of experts have proposed
      "preferred regimens" of antiretroviral treatment (ART) as initial therapy in HIV
      infected patients for 2013. The objective of this study is to evaluate the costs
      and effectiveness of initiating treatment with these "preferred regimens".
      METHODS: An economic assessment of costs and effectiveness (cost/effectiveness)
      was performed using decision tree analysis models. Effectiveness was defined as
      the probability of having viral load <50copies/mL at week48, in an intention-to
      treat analysis. Cost of initiating treatment with an ART regime was defined as
      the costs of ART and its consequences (adverse effects, changes of ART regime and
      drug resistance analyses) during the first 48weeks. The perspective of the
      analysis is that of the National Health System was applied, only taking into
      account differential direct costs: ART (official prices), management of adverse
      effects, resistance studies, and determination of HLA B*5701. The setting is
      Spain and the costs are those of 2013. A sensitivity deterministic analysis was
      performed, constructing three scenarios for each regimen: baseline, most
      favourable, and most unfavourable cases. RESULTS: In the baseline case scenario,
      the cost of initiating treatment ranges from 6,747euros for TDF/FTC+NVP to
      12,059euros for TDF/FTC+RAL. The effectiveness ranges between 0.66 for
      ABC/3TC+LPV/r and ABC/3TC+ATV/r, and 0.87 for TDF/FTC+RAL and ABC/3TC+RAL.
      Effectiveness, in terms of cost/effectiveness, varies between 8,396euros and
      13,930euros per responder at 48weeks, for TDF/FTC/RPV and TDF/FTC+RAL,
      respectively. CONCLUSIONS: Taking ART at official prices, the most effective
      regimen was TDF/FTC/RPV, followed by the rest of non-nucleoside containing
      regimens. The sensitivity analysis confirms the robustness of these findings.

PMID- 23969277
TI  - Switching from MAPK-dependent to MAPK-independent repression of the sodium-iodide
      symporter in 2D and 3D cultured normal thyroid cells.
AB  - Loss of sodium-iodide symporter (NIS) expression in thyroid tumour cells
      primarily caused by constitutive MAPK pathway activation is often refractory to
      small molecule MAPK inhibitors. Suggested mechanisms are rebound MAPK signalling
      and activation of alternative signalling pathways. Here we provide evidence that
      failure to recover down-regulated NIS by MEK inhibition is not specific to tumour
      cells. NIS mRNA levels remained repressed in TSH-stimulated primary thyroid cells
      co-treated with epidermal growth factor (EGF) and pan-MEK inhibitor U0126 in the
      presence of 5% fetal bovine serum or, independently of serum, in 3D cultured
      thyroid follicles. This led to inhibited iodide transport and iodination. In
      contrast, U0126 restituted thyroglobulin synthesis in EGF-treated follicular
      cells. Serum potentiated TSH-stimulated NIS expression in 2D culture. U0126
      blocked down-regulation of NIS only in serum-starved cells with a diminished TSH
      response. Together, this suggests that morphogenetic signals modify the
      expression of NIS and recovery response to MEK inhibition. 

PMID- 23969278
TI  - Screening interval for celiac disease in patients with type 1 diabetes mellitus.

PMID- 23969279
TI  - A new method to detect cerebral blood flow waveform in synchrony with chest
      compression by near-infrared spectroscopy during CPR.
AB  - OBJECTIVE: The objective of the study is to demonstrate the utility of near
      infrared spectroscopy (NIRS) in evaluating chest compression (CC) quality in
      cardiac arrest (CA) patients as well as determine its prognosis predictive value.
      METHODS: We present a nonconsecutive case series of adult patients with CA whose
      cardiopulmonary resuscitation (CPR) was monitored with NIRS and collected the
      total hemoglobin concentration change (DeltacHb), the tissue oxygen index (TOI),
      and the DeltaTOI to assess CC quality in a noninvasive fashion. RESULTS: During
      CPR, DeltacHb displayed waveforms monitor, which we regarded as a surrogate for
      CC quality. Total hemoglobin concentration change waveforms responded accurately
      to variations or cessations of CCs. In addition, a TOI greater than 40% measured
      upon admission appears to be significant in predicting patient's outcome. Of 15
      patients, 6 had a TOI greater than 40% measured upon admission, and 67% of the
      latter were in return of spontaneous circulation after CPR and were found to be
      significantly different between return of spontaneous circulation and death (P =
      .047; P < .05). CONCLUSION: Near-infrared spectroscopy reliably assesses the
      quality of CCs in patients with CA demonstrated by synchronous waveforms during
      CPR and possible prognostic predictive value, although further investigation is
      warranted.

PMID- 23969280
TI  - Real-time 3-dimensional contrast-enhanced ultrasound in detecting hemorrhage of
      blunt renal trauma.
AB  - OBJECTIVES: The objective of this study is to evaluate the diagnostic value of
      real-time 3-dimensional contrast-enhanced ultrasound in the hemorrhage of blunt
      renal trauma. METHODS: Eighteen healthy New Zealand white rabbits were randomly
      divided into 3 groups. Blunt renal trauma was performed on each group by using
      minitype striker. Ultrasonography, color Doppler flow imaging, and contrast
      enhanced 2-dimensional and real-time 3-dimensional ultrasound were applied before
      and after the strike. The time to shock and blood pressure were subjected to
      statistical analysis. Then, a comparative study of ultrasound and pathology was
      carried out. RESULTS: All the struck kidneys were traumatic. In the
      ultrasonography, free fluid was found under the renal capsule. In the color
      Doppler flow imaging, active hemorrhage was not identified. In 2-dimensional
      contrast-enhanced ultrasound, active hemorrhage of the damaged kidney was
      characterized. Real-time 3-dimensional contrast-enhanced ultrasound showed a real
      time and stereoscopic ongoing bleeding of the injured kidney. The wider the
      hemorrhage area in 4-dimensional contrast-enhanced ultrasound was, the faster the
      blood pressure decreased. CONCLUSIONS: Real-time 3-dimensional contrast-enhanced
      ultrasound is a promising noninvasive tool for stereoscopically and vividly
      detecting ongoing hemorrhage of blunt renal trauma in real time.

PMID- 23969282
TI  - Evaluation of photocatalytic activities of supported catalysts on NaX zeolite or
      activated charcoal.
AB  - This study aimed to evaluate the photocatalytic activity of ZnO and Nb2O5
      catalysts, both supported on NaX zeolite and activated charcoal (AC). The
      synergistic effect between oxide and support and the influence of solution pH (3,
      7 and 9) on photocatalytic degradation of reactive blue 5G (C.I. 222) were
      analyzed. The catalysts Nb2O5/NaX, Nb2O5/AC and ZnO/NaX, ZnO/AC with 5 and 10%
      (wt%) were prepared by wet impregnation. The results showed that the catalysts
      exhibit quite different structural and textural properties. The synergic effect
      between ZnO and NaX support was higher than that with the activated charcoal,
      showing that these catalysts were more efficient. The most photoactive catalyst
      was 10% ZnO/NaX which showed 100% discoloration of the dye solution at pH 3, 7
      and 9 after 0.5, 5 and 2h of irradiation, respectively. The hydrolytic nature of
      zeolite favored the formation of surface hydroxyl radicals, which increased the
      activity of the photocatalyst. Thus, catalysts supported on NaX zeolite are
      promising for use in photocatalysis.

PMID- 23969283
TI  - An environmental forensic procedure to analyse anthropogenic pressures of urban
      origin on surface water of protected coastal agro-environmental wetlands
      (L'Albufera de Valencia Natural Park, Spain).
AB  - Detection and spatial distribution of 14 drugs of abuse and 17 pharmaceuticals in
      surface waters was investigated to determine transport hydrological connectivity
      between urban, agriculture and natural environments. Solid-phase extraction and
      liquid chromatography tandem mass spectrometry was applied to all samples. To
      determine spatial incidence of contaminants, analytical results of target
      compounds were georeferenced and integrated into a geographical information
      systems structure together with layers of municipal population, location of
      sewage water treatment plants and irrigation channels and sectors. The
      methodology was applied to L'Albufera Natural Park in Valencia (Spain). A total
      of 9 drugs of abuse were detected at 16 points (76% of the sample sites). Cocaine
      and its metabolite, benzoylecgonine, were the most detected substances, being
      found in 12 and 16 samples, respectively. Maximum concentrations were found in
      benzoylecgonine (78.71 ng/L) and codeine (51.60 ng/L). Thirteen pharmaceuticals
      were found at 16 points. The most detected compounds were carbamazepine (15
      samples) and ibuprofen (11 samples). Maximum concentrations were detected in
      acetaminophen (17,699.4 ng/L), ibuprofen (3913.7 ng/L) and codeine (434.0 ng/L).
      Spatial distribution of pharmaceuticals showed a clear relationship between
      irrigation areas, high population densities municipalities (above 1000 h/km(2))
      and sewage water treatment plants.

PMID- 23969281
TI  - Relief of cannabis withdrawal symptoms and cannabis quitting strategies in people
      with schizophrenia.
AB  - This study examined the response to cannabis withdrawal symptoms and use of
      quitting strategies to maintain abstinence in people with schizophrenia. A
      convenience sample of 120 participants with schizophrenia who had at least weekly
      cannabis use and a previous quit attempt without formal treatment were
      administered the 176-item Marijuana Quit Questionnaire to characterize their
      "most serious" (self-defined) quit attempt. One hundred thirteen participants had
      withdrawal symptoms, of whom 104 (92.0%) took some action to relieve a symptom,
      most commonly nicotine use (75%). 90% of withdrawal symptoms evoked an action for
      relief in a majority of participants experiencing them, most frequently anxiety
      (95.2% of participants) and cannabis craving (94.4%). 96% of participants used
      one or more quitting strategies to maintain abstinence during their quit attempt,
      most commonly getting rid of cannabis (72%) and cannabis paraphernalia (67%).
      Religious support or prayer was the quitting strategy most often deemed "most
      helpful" (15%). Use of a self-identified most helpful quitting strategy was
      associated with significantly higher one-month (80.8% vs. 73.6%) and one-year
      (54.9% vs. 41.3%) abstinence rates. Actions to relieve cannabis withdrawal
      symptoms in people with schizophrenia are common. Promotion of effective quitting
      strategies may aid relapse prevention. 

PMID- 23969285
TI  - Comparative DNA damage and oxidative effects of carcinogenic and non-carcinogenic
      sediment-bound PAHs in the gills of a bivalve.
AB  - Polycyclic aromatic hydrocarbons (PAHs) regarded as carcinogenic and non
      carcinogenic to humans are ubiquitous hydrophobic pollutants that tend to be
      trapped in aquatic sediments. As a consequence of their acknowledged toxicity and
      pro-mutagenic or even carcinogenic potential, PAHs are deemed prioritary in
      biomonitoring programmes. Still, the differences between the toxicity of
      carcinogenic and non-carcinogenic PAHs are poorly known especially, when aquatic
      organisms are exposed to ecologically-relevant concentrations of these compounds
      in sediments. Laboratory bioassays with sediments spiked with phenanthrene (Phe)
      and benzo[b]fluoranthene (B[b]F), non-carcinogenic and carcinogenic PAH,
      respectively, were conducted and the effects of exposure (related to DNA damage
      and oxidative stress) were analyzed in the gills of a burrowing clam, Ruditapes
      decussatus (Bivalvia, Veneridae). To ensure ecological relevance, two contaminant
      concentrations (termed "low" and "high") were selected in accordance with
      available PAH sediment quality guidelines. The results showed that, even in "low"
      concentrations, both compounds caused a likely genotoxic effect in the gills,
      which is in accordance with the link between PAHs in water. Glutathione S
      transferase activity and glutathione biosynthesis appear to be associated with
      limited lipid peroxidation even though they were insufficient to prevent higher
      and faster genotoxicity induced by exposure to the carcinogenic B[b]F,
      comparative to Phe. Overall the findings indicate that low concentrations of
      sediment-bound PAHs, carcinogenic or not, may be rendered significantly
      bioavailable to benthic filter-feeders as to induce genotoxicity, revealing that
      even PAHs considered non-carcinogenic to humans detain a latent, albeit
      significant, pro-mutagenic hazard to bivalve molluscs. 

PMID- 23969284
TI  - A(1) and A(3) adenosine receptors inhibit LPS-induced hypoxia-inducible factor-1
      accumulation in murine astrocytes.
AB  - Adenosine (Ado) exerts neuroprotective and anti-inflammatory functions by acting
      through four receptor subtypes A1, A2A, A2B and A3. Astrocytes are one of its
      targets in the central nervous system. Hypoxia-inducible factor-1 (HIF-1), a
      master regulator of oxygen homeostasis, is induced after hypoxia, ischemia and
      inflammation and plays an important role in brain injury. HIF-1 is expressed by
      astrocytes, however the regulatory role played by Ado on HIF-1alpha modulation
      induced by inflammatory and hypoxic conditions has not been investigated. Primary
      murine astrocytes were activated with lipopolysaccharide (LPS) with or without
      Ado, Ado receptor agonists, antagonists and receptor silencing, before exposure
      to normoxia or hypoxia. HIF-1alpha accumulation and downstream genes regulation
      were determined. Ado inhibited LPS-increased HIF-1alpha accumulation under both
      normoxic and hypoxic conditions, through activation of A1 and A3 receptors. In
      cells incubated with the blockers of p44/42 MAPK and Akt, LPS-induced HIF-1alpha
      accumulation was significantly decreased in normoxia and hypoxia, suggesting the
      involvement of p44/42 MAPK and Akt in this effect and Ado inhibited kinases
      phosphorylation. A series of angiogenesis and metabolism related genes were
      modulated by hypoxia in an HIF-1 dependent way, but not further increased by LPS,
      with the exception of GLUT-1 and hexochinase II that were elevated by LPS only in
      normoxia and inhibited by Ado receptors. Instead, genes involved in inflammation,
      like inducible nitric-oxide synthase (iNOS) and A2B receptors, were increased by
      LPS in normoxia, strongly stimulated by LPS in concert with hypoxia and inhibited
      by Ado, through A1 and A3 receptor subtypes. In conclusion A1 and A3 receptors
      reduce the LPS-mediated HIF-1alpha accumulation in murine astrocytes, resulting
      in a downregulation of genes involved in inflammation and hypoxic injury, like
      iNOS and A2B receptors, in both normoxic and hypoxic conditions. 

PMID- 23969286
TI  - BpTRUth: do automated blood pressure monitors outperform mercury?
AB  - Manual measurement of blood pressure (BP) in the office (MOBP) is inferior in
      accuracy when compared with ambulatory BP measurements (ABPM) since it misses
      white coat and masked effects on BP. BpTRU, an automated office BP device (AOBP),
      has been reported to reduce white coat effect. We performed a retrospective
      review of the diagnostic accuracy of MOBP (taken by a trained nurse in clinical
      hypertension) and AOBP using the Bland-Altman method in hypertensive patients
      referred to a Renal Hypertension Clinic. In 329 hypertensive patients, the 95%
      limits of agreement between systolic AOBP and ABPM were -31 mm Hg to 33 mm Hg and
      for MOBP and ABPM were -27.8 mm Hg to 37.4 mm Hg. The bias between systolic MOBP
      and systolic ABPM was 4.9 mm Hg (95% confidence interval, 3.0-6.6 mm Hg) whereas
      the bias between the systolic AOBP and the systolic ABPM was -3.2 (95% confidence
      interval, -1.3 to -5.0). AOBP did not improve treatment relevant classification
      errors compared with MOBP (28% vs. 23%; P = .052). Our data support findings by
      others showing that AOBP improves, but does not eliminate, white coat effect. The
      increased detection of white coat effect appears related to systematic downward
      bias by BpTRU. As a result, detection of masked effect is undermined by BpTRU. 

PMID- 23969287
TI  - Perception of uncontrolled blood pressure and non-adherence to anti-hypertensive
      agents in diabetic hypertensive patients.
AB  - We assessed the association between adherence to antihypertensive drug treatment
      and patient's perception of uncontrolled blood pressure (BP) in diabetic
      hypertensive subjects. This was a cross-sectional study that evaluated adherence
      to antihypertensives (Morisky questionnaire), patients' perception of abnormal
      BP, office BP, and ambulatory BP monitoring in diabetic hypertensive subjects. We
      evaluated 323 patients, 65.2% women, aged 56.5 +/- 7 years, glycosylated
      hemoglobin (HbA1c) 8.0% (range, 6.9%-9.6%), diabetes duration of 10 years (range,
      5-17 years). Adherence to drug treatment was 51.4%. Patients who reported
      hypertension-related symptoms (60.4%) had a lower level of adherence (P < .001).
      Non-adherence occurred four times more frequently in patients who reported
      hypertension-related symptoms (P < .001, adjusted for use of three or more anti
      hypertensives, age, and duration of diabetes). Non-adherents had higher office
      diastolic BP (83.6 +/- 11.9 vs. 79.8 +/- 9.9; P = .003), but no difference
      between groups was observed considering systolic, diastolic, and mean BP
      evaluated by ambulatory BP monitoring. Low rates of adherence to antihypertensive
      drug treatment were observed in outpatient hypertensive diabetic subjects.
      Perception of uncontrolled BP levels was strongly and independently associated
      with non-adherence. Non-adherence determined repercussion on office BP that may
      have clinical implications in cardiovascular risk. 

PMID- 23969288
TI  - A prospective, assessor-blind evaluation of surgeon-performed transcutaneous
      laryngeal ultrasonography in vocal cord examination before and after
      thyroidectomy.
AB  - INTRODUCTION: Transcutaneous laryngeal ultrasonography (TLUSG) is a promising
      alternative to direct laryngoscopy in assessing perioperative vocal cord
      function. This study sought to evaluate the accuracy of TLUSG in assessing vocal
      cord function. METHODS: Altogether, 204 patients underwent TLUSG and direct
      laryngoscopy before and after elective thyroidectomy. For both examinations,
      vocal cord movements were independently graded. Grade I meant both vocal cords
      had normal movement; grade II meant >=1 vocal cord had decreased movement; and
      grade III meant >=1 vocal cord had no movement. Grade II or III on direct
      laryngoscopy was defined as vocal cord paresis or palsy (VCP). To assess
      accuracy, TLUSG findings were correlated with direct laryngoscopy findings.
      RESULTS: No patient had preoperative VCP, and 17 had unilateral postoperative
      VCP. The overall postoperative VCP rate was 5.1%. TLUSG failed to assess VCs in
      11 (5.4%) postoperative patients. Of these, 2 had VCP and 9 had no VCP on direct
      laryngoscopy. Postoperative TLUSG had a sensitivity, specificity, positive
      predictive value, and negative predictive value of 93.3%, 97.8%, 77.8%, and
      99.4%, respectively. Of the 175 patients with grade I on TLUSG, only 1 (<1%) had
      grade II VCP on direct laryngoscopy. CONCLUSION: TLUSG is a promising,
      noninvasive tool for selecting patients to undergo direct laryngoscopy before and
      after thyroidectomy.

PMID- 23969289
TI  - [Oocyte vitrification in an ART laboratory].
AB  - Oocyte vitrification has been authorized in France after the modification of
      French bioethics law in July 2011. This evolution will bring a dramatic change in
      patients' management since, from 2011, infertile couples, oocyte donation and
      fertility preservation programs will benefit this technique in France. We have
      introduced oocyte vitrification in our ART laboratory through a validation of the
      method using Evidence-Based Medicine model: open system Cryotop, Ethylene-glycol
      15% and DMSO 15%. Based on our 1-year experience, oocyte vitrification upgrades
      our daily practice while also minimizing embryo cryoconservation as recommended
      by the law. 

PMID- 23969290
TI  - Efficient in vivo depletion of CD8(+) T lymphocytes in common marmosets by novel
      CD8 monoclonal antibody administration.
AB  - In order to directly demonstrate the roles of CD8(+) T lymphocytes in non-human
      primates, in vivo depletion of the CD8(+) T cells by administration of a CD8
      specific monoclonal antibody (mAb) is one of the crucial techniques. Recently,
      the common marmoset (Callithrix jacchus), which is classified as a New World
      monkey, has been shown useful as an experimental animal model for various human
      diseases such as multiple sclerosis, Parkinson's disease and a number of
      infectious diseases. Here we show that an anti-marmoset CD8 mAb 6F10, which we
      have recently established, efficiently depletes the marmoset CD8(+) T lymphocytes
      in vivo, i.e., the administration of 6F10 induces drastic and specific reduction
      in the ratio of the CD8(+) T cell subset for at least three weeks or longer. Our
      finding will help understand the pivotal role of CD8(+) T cells in vivo in the
      control of human diseases. 

PMID- 23969291
TI  - Characterization of a multifunctional alpha2,3-sialyltransferase from Pasteurella
      dagmatis.
AB  - A new multifunctional alpha2,3-sialyltransferase has been discovered in
      Pasteurella dagmatis. The enzyme, in short PdST, was identified from the P.
      dagmatis genome by sequence similarity with sialyltransferases of
      glycosyltransferase family GT-80. In addition to its regioselective
      sialyltransferase activity (5.9 U/mg; pH 8.0), purified PdST is alternatively
      active at low pH as alpha2,3-sialidase (0.5 U/mg; pH 4.5) and alpha2,3-trans
      sialidase (1.0 U/mg; pH 4.5). It also shows cytidine-5'-monophosphate N-acetyl
      neuraminic (CMP-Neu5Ac) hydrolase activity (3.7 U/mg; pH 8.0) when no sialyl
      acceptor substrate is present in the reaction. After sialyltransferase PmST1 from
      P. multocida, PdST is the second member of family GT-80 to display this
      remarkable catalytic promiscuity. A unique feature of PdST, however, is a
      naturally occurring Ser-to-Thr substitution within a highly conserved
      Y(112)DDGS(116) sequence motif. In PmST1, the equivalent Ser(143) is involved in
      binding of the CMP-Neu5Ac donor substrate. Reversion of the natural mutation in a
      T116S-PdST variant resulted in a marked increase in alpha2,3-trans-sialidase side
      activity (4.0 U/mg; pH 4.5), whereas the major sialyltransferase activity was
      lowered (3.8 U/mg; pH 8.0). The Michaelis-Menten constant for CMP-Neu5Ac was
      decreased 4-fold in T116S mutant when compared with wild-type PdST (KM=1.1 mM),
      indicating that residue 116 of PdST contributes to a delicate balance between
      substrate binding and catalytic activity. D-Galactose and various beta-D
      galactosides function as sialyl acceptors from CMP-Neu5Ac, whereas other hexoses
      (e.g. D-glucose) are inactive. Structure comparison was used to rationalize the
      particular acceptor substrate specificity of PdST in relation to other GT-80
      sialyltransferases that show strict alpha2,3-regioselectivity, but are flexible
      in using alpha/beta-galactosides for sialylation.

PMID- 23969292
TI  - Myasthenia gravis in association with extrathymic neoplasia.

PMID- 23969293
TI  - Neurological syndromes associated with medication use.

PMID- 23969295
TI  - Statement of the Spanish Interdisciplinary Cardiovascular Prevention Committee
      (CEIPC for its Spanish acronym) on the 2012 European Cardiovascular Prevention
      Guidelines.
AB  - Based on the two main frameworks for evaluating scientific evidence (SEC and
      GRADE) European cardiovascular prevention guidelines recommend interventions
      across all life stages using a combination of population-based and high-risk
      strategies with diet as the cornerstone of prevention. The evaluation of
      cardiovascular risk (CVR) incorporates HDL levels and psychosocial factors, a
      very high risk category, and the concept of age-risk. They also recommend
      cognitive-behavioural methods (e.g., motivational interviewing, psychological
      interventions) led by health professionals and with the participation of the
      patient's family, to counterbalance psychosocial stress and reduce CVR through
      the institution of positive habits such as a healthy diet, physical activity,
      smoking cessation, and adherence to treatment. Additionally, public health
      interventions - such as smoking ban in public areas or the elimination of trans
      fatty acids from the food chain - are also essential. Other innovations include
      abandoning antiplatelet therapy in primary prevention and the recommendation of
      maintaining blood pressure within the 130-139/80-85 mmHg range in diabetic
      patients and individuals with high CVR. Finally, due to the significant impact on
      patient progress and medical costs, special emphasis is given to the low
      therapeutic adherence levels observed. In sum, improving cardiovascular
      prevention requires a true partnership among the political class, public
      administrations, scientific and professional associations, health foundations,
      consumer associations, patients and their families. Such partnership would
      promote population-based and individual strategies by taking advantage of the
      broad spectrum of scientific evidence available, from clinical trials to
      observational studies and mathematical models to evaluate population-based
      interventions, including cost-effectiveness analyses.

PMID- 23969294
TI  - Workload of on-call emergency room neurologists in a Spanish tertiary care
      centre. A one-year prospective study.
AB  - INTRODUCTION: Population ageing, the rising demand for healthcare, and the
      establishment of acute stroke treatment programs have given rise to increases in
      the number and complexity of neurological emergency cases. Nevertheless, many
      centres in Spain still lack on-call emergency neurologists. METHODS: We conducted
      a retrospective study to describe the role of on-call neurologists at Hospital
      General Universitario Gregorio Maranon, a tertiary care centre in Madrid, Spain.
      Sociodemographic characteristics, most common pathologies, diagnostic tests, and
      destination of the patients attended were recorded daily using a computer
      database. Results were compared with the general care data from the emergency
      department. RESULTS: The team attended 3234 patients (3.48% of the emergency
      department total). The mean number of patients seen per day was 11.15. The most
      frequent pathologies were stroke (34%), epilepsy (16%) and headache (8%). The
      mean stay in the emergency department was 7.17 hours. Hospital admission rate was
      40% (7.38% of emergency hospital admissions). The main destinations for admitted
      patients were the stroke unit (39.5%) and the neurology department (33%).
      Endovascular or thrombolytic therapies were performed on 76 occasions. Doctors
      attended 70% of the patients during on-call hours. CONCLUSIONS: Emergency
      neurological care is varied, complex, and frequently necessary. Neurological
      cases account for a sizeable percentage of both patient visits to the emergency
      room and the total number of emergency admissions. The current data confirm that
      on-call neurologists available on a 24-hour basis are needed in emergency
      departments.

PMID- 23969296
TI  - A comparison of early diagnostic utility of Alzheimer disease biomarkers in brain
      magnetic resonance and cerebrospinal fluid.
AB  - INTRODUCTION: The goals of this study were to compare the early diagnostic
      utility of Alzheimer disease biomarkers in the CSF with those in brain MRI in
      conditions found in our clinical practice, and to ascertain the diagnostic
      accuracy of both techniques used together. METHODS: Between 2008 and 2009, we
      included 30 patients with mild cognitive impairment (MCI) who were examined using
      1.5 Tesla brain MRI and AD biomarker analysis in CSF. MRI studies were evaluated
      by 2 radiologists according to the Korfs visual scale. CSF biomarkers were
      analysed using INNOTEST reagents for Abeta1-42, total-tau and phospho-tau181p. We
      evaluated clinical changes 2 years after inclusion. RESULTS: By 2 years after
      inclusion, 15 of the original 30 patients (50%) had developed AD (NINCDS-ADRA
      criteria). The predictive utility of AD biomarkers in CSF (RR 2.7; 95% CI, 1.1
      6.7; P<.01) was greater than that of MRI (RR 1.5; 95% CI 95%, 0.7-3.4; P<.2);
      using both techniques together yielded a sensitivity and a negative predictive
      value of 100%. Normal results on both complementary tests ruled out progression
      to AD (100%) within 2 years of inclusion. CONCLUSIONS: Our results show that the
      diagnostic accuracy of biomarkers in CSF is higher than that of biomarkers in
      MRI. Combined use of both techniques is highly accurate for either early
      diagnosis or exclusion of AD in patients with MCI.

PMID- 23969297
TI  - Hirayama disease: Is surgery an option?
AB  - INTRODUCTION: Hirayama disease is a rare cervical myelopathy, predominantly
      affecting young males, which presents with distal atrophy of the upper limbs as
      its first and main symptom. It must be differentiated from motor neuron diseases
      because its natural history is different and because HD tends to stabilise in
      less than 5 years. Diagnosis is based on clinical findings and dynamic flexion
      MRI showing segmental spinal muscular atrophy, detachment of the posterior dura
      mater and venous congestion in the epidural space. The tendency is to indicate
      conservative treatment and no indications for surgery have been established.
      PATIENTS: We present 4 cases meeting both clinical criteria and dynamic MRI
      imaging criteria for a diagnosis of Hirayama disease. Two have stabilised
      spontaneously over the course of many years, and MRI scans show that typical
      changes have disappeared. Another case also remains stable following a shorter
      observation time. The fourth case is a young man who developed severe myelopathy
      in just over a year, and therefore underwent surgery. While his follow-up time is
      still short, his condition remains stable. CONCLUSIONS: Our 4 cases suggest that
      the condition of most patients with Hirayama stabilises naturally; patients
      should be evaluated for surgery on an individual basis, and surgery should
      probably be limited to the most severe cases that have progressed quickly.

PMID- 23969298
TI  - The role of response inhibition in temporal preparation: evidence from a go/no-go
      task.
AB  - During the foreperiod (FP) of a warned reaction task, participants engage in a
      process of temporal preparation to speed response to the impending target
      stimulus. Previous neurophysiological studies have shown that inhibition is
      applied during FP to prevent premature response. Previous behavioral studies have
      shown that the duration of FP on both the current and the preceding trial
      codetermine response time to the target. Integrating these findings, the present
      study tested the hypothesis that the behavioral effects find their origin in
      response inhibition on the preceding trial. In two experiments the variable-FP
      paradigm was combined with a go/no-go task, in which no-go stimuli required
      explicit response inhibition. The resulting data pattern revealed sequential
      effects of both FP (long or short) and response requirement (go or no-go), which
      could be jointly understood as expressions of response inhibition, consistent
      with the hypothesis. 

PMID- 23969299
TI  - Perceptual load does not modulate auditory distractor processing.
AB  - In vision, it is well established that the perceptual load of a relevant task
      determines the extent to which irrelevant distractors are processed. Much less
      research has addressed the effects of perceptual load within hearing. Here, we
      provide an extensive test using two different perceptual load manipulations,
      measuring distractor processing through response competition and awareness
      report. Across four experiments, we consistently failed to find support for the
      role of perceptual load in auditory selective attention. We therefore propose
      that the auditory system - although able to selectively focus processing on a
      relevant stream of sounds - is likely to have surplus capacity to process
      auditory information from other streams, regardless of the perceptual load in the
      attended stream. This accords well with the notion of the auditory modality
      acting as an 'early-warning' system as detection of changes in the auditory scene
      is crucial even when the perceptual demands of the relevant task are high. 

PMID- 23969301
TI  - A novel association of two non-synonymous polymorphisms in PER2 and PER3 genes
      with specific diurnal preference subscales.
AB  - The circadian system is responsible for the generation and maintenance of
      physiological and behavioral rhythms in mammals and allows synchronization with
      the environment. Different polymorphisms in clock genes have been studied in
      healthy humans, providing inconsistent results in different populations. In this
      study, we evaluated the possibility that two non-synonymous polymorphisms in PER2
      (p.Gly1244Glu, rs934945) and PER3 (p.Met1028Thr, rs2640909) genes might be
      associated with diurnal preference in healthy Colombian subjects. A total of 209
      Colombian university students were genotyped for two functional polymorphisms in
      PER2 and PER3 genes (rs934945 and rs2640909). We applied the composite scale of
      morningness (CSM) to measure phenotypic patterns of human diurnal preference.
      Additionally, we extracted from the CSM three subscale scores ("morningness",
      "activity planning" and "morning alertness"). We used a false discovery rate
      approach (q values) for correction of multiple testing. PER2 (rs934945) showed a
      significant association with two CSM subscale scores: "activity planning" and
      "morning alertness". For PER3 (rs2640909), we observed an association with the
      "morningness" CSM subscale scores. We found a significant association between
      novel and functional polymorphisms in PER2 and PER3 genes with specific CSM
      subscales for diurnal preference. We showed for the first time the association of
      rs934945 with "morning alertness" and rs2640909 with "morningness". We suggest
      that these results should be replicated in order to confirm the association in
      other populations. Finally, the study of additional novel functional
      polymorphisms in other clock genes could be of relevance for a deep understanding
      of circadian phenotypes and neuropsychiatric disorders. 

PMID- 23969300
TI  - Opioid and noradrenergic contributions of tapentadol in experimental neuropathic
      pain.
AB  - Tapentadol is a dual action molecule with mu opioid agonist and norepinephrine
      (NE) reuptake blocking activity that has recently been introduced for the
      treatment of moderate to severe pain. The effects of intraperitoneal (i.p.)
      morphine (10mg/kg), tapentadol (10 or 30 mg/kg) or duloxetine (30 mg/kg), a
      norepinephrine/serotonin (NE/5HT) reuptake inhibitor, were evaluated in male,
      Sprague-Dawley rats with spinal nerve ligation (SNL) or sham surgery.
      Additionally, the effects of these drugs on spinal cerebrospinal fluid (CSF) NE
      levels were quantified. Response thresholds to von Frey filament stimulation
      decreased significantly from baseline in SNL, but not sham, operated rats.
      Duloxetine, tapentadol and morphine produced significant and time-related
      reversal of tactile hypersensitivity. Duloxetine significantly increased spinal
      CSF NE levels in both sham and SNL rats and no significant differences were
      observed in these groups. Tapentadol (10 mg/kg) produced a significant increase
      in spinal NE levels in SNL, but not in sham, rats. At the higher dose (30 mg/kg),
      tapentadol produced a significant increase in spinal CSF NE levels in both SNL
      and sham groups; however, spinal NE levels were elevated for an extended period
      in the SNL rats. This could be detected 30 min following tapentadol (30 mg/kg) in
      both sham and SNL groups. Surprisingly, while the dose of morphine studied
      reversed tactile hypersensitivity in nerve-injured rats, CSF NE levels were
      significantly reduced in both sham- and SNL rats. The data suggest that
      tapentadol elicits enhanced elevation in spinal NE levels in a model of
      experimental neuropathic pain offering a mechanistic correlate to observed
      clinical efficacy in this pain state.

PMID- 23969302
TI  - Discovering unhealthiness: evidence from cluster analysis.
AB  - PURPOSE: This study examines information on an array of health limitations,
      chronic conditions, treatments, and drug consumptions to reveal the prevalence
      and severity of unhealthiness that are not directly observed. METHODS: Cluster
      analysis is applied to 265,468 individuals who participated in the 45 and Up
      Study in Australia. RESULTS: Among the study participants, 8% of those age 45-54
      years, 10% of those age 55-64, 13% of those age 65-74, and 17% of those age 75
      and older were classified as unhealthy. For the youngest individuals,
      unhealthiness is characterized by moderate-to-high mental distress, a poor
      physical health score equivalent to the score associated with having four major
      limitations in physical functioning, teeth health less than good, and having been
      diagnosed with at least two chronic conditions. The oldest individuals also
      suffer from these limitations, as well as dependence on at least three different
      drug groups and two medical treatments, but they are in better mental health
      state. CONCLUSIONS: Understanding unhealthiness across population groups will
      result in more effective allocation of health resources. Older populations
      require more resources to be devoted to the management of physical health and
      chronic illnesses.

PMID- 23969303
TI  - Is exposure to secondhand smoke associated with cognitive parameters of children
      and adolescents?--a systematic literature review.
AB  - PURPOSE: Despite the known association of second hand smoke (SHS) with increased
      risk of ill health and mortality, the effects of SHS exposure on cognitive
      functioning in children and adolescents are unclear. Through a critical review of
      the literature we sought to determine whether a relationship exists between these
      variables. METHODS: The authors systematically reviewed articles (dated 1989
      2012) that investigated the association between SHS exposure (including in utero
      due to SHS exposure by pregnant women) and performance on neurocognitive and
      academic tests. Eligible studies were identified from searches of Web of
      Knowledge, MEDLINE, Science Direct, Google Scholar, CINAHL, EMBASE, Zetoc, and
      Clinicaltrials.gov. RESULTS: Fifteen articles were identified, of which 12 showed
      inverse relationships between SHS and cognitive parameters. Prenatal SHS exposure
      was inversely associated with neurodevelopmental outcomes in young children,
      whereas postnatal SHS exposure was associated with poor academic achievement and
      neurocognitive performance in older children and adolescents. Furthermore, SHS
      exposure was associated with an increased risk of neurodevelopmental delay.
      CONCLUSIONS: Recommendations should be made to the public to avoid sources of SHS
      and future research should investigate interactions between SHS exposure and
      other risk factors for delayed neurodevelopment and poor cognitive performance.

PMID- 23969304
TI  - Evaluation of health advisory service for H7N9 control in China.

PMID- 23969305
TI  - A post hoc pooled analysis of exacerbations among US participants in randomized
      controlled trials of tiotropium.
AB  - BACKGROUND: Exacerbations are a defining outcome of chronic obstructive pulmonary
      disease (COPD). We evaluated the effect of tiotropium on COPD exacerbations and
      related hospitalizations among patients from the USA enrolled in clinical trials.
      METHODS: Data were pooled from six randomized, double-blind, placebo-controlled
      trials (6 to >= 12 months' duration) of tiotropium in patients with COPD.
      Exacerbations were defined retrospectively as an increase in or new onset of >1
      respiratory symptom lasting for >= 3 days and requiring treatment with systemic
      corticosteroids and/or antibiotics. Time to first exacerbation or hospitalization
      and exacerbation rates were analyzed at 6 months, and at 1 year for studies >= 1
      year. RESULTS: In total, 4355 patients (tiotropium, 2268, placebo, 2087; mean age
      66.5 years; forced expiratory volume in 1 s [FEV1] 1.03 L [35.5% predicted]) were
      analyzed at 6 months and 2455 at 1 year (tiotropium 1317, placebo 1138; mean age
      65.5 years; FEV1 1.03 L [37.0% predicted]). Tiotropium delayed time to first
      exacerbation or first hospitalized exacerbation at 6 months (hazard ratios [HRs],
      0.80, 0.65, respectively; p < 0.001 vs placebo) and 1 year (HRs, 0.73 and 0.55; p
      < 0.001 vs placebo) and reduced exacerbation rates and hospitalization rates (6
      months: HRs, 0.79, 0.64; 1 year: HRs, 0.78, 0.56, respectively; all p < 0.01 vs
      placebo). Tiotropium significantly reduced exacerbations, irrespective of inhaled
      corticosteroid use at baseline. Tiotropium was not associated with an increased
      risk of cardiac-related events. CONCLUSIONS: Tiotropium significantly reduced the
      risk and rates of exacerbations and hospitalizations among US patients with COPD.

PMID- 23969306
TI  - [Management of vaginal carcinoma in patients over 70 years old: advantage of a
      radiotherapy-brachytherapy association].
AB  - OBJECTIVE: Report and discuss the management of the primitive vaginal cancer in
      elderly adults at a single institute. PATIENTS AND METHODS: Data from patients
      more than 70 year-old treated for a primitive vaginal cancer at the Institut de
      Cancerologie de la Loire Lucien-Neuwirth was retrospectively collected. RESULTS:
      From August 1999 to January 2009, 9/24 patients treated for a primitive vaginal
      cancer had more than 70 year-old. The median age was 81 years (7-94 years). Most
      patients had a performance status less or equal to 1 (n=6), a squamous cell
      carcinoma (n=7) and a FIGO stage less or equal to II (n=6). All patients were
      treated with 3D external beam radiation, 3 received concurrent chemotherapy, 3
      had a supplementary brachytherapy, and 6 had a colpohysterectomy. Among 7
      evaluable patients, there were 4 complete responses, 2 partial responses and one
      progression. Main acute toxicities were gastrointestinal (n=5), urinary (n=3),
      general (n=3) and cutaneous (n=2). Three patients experienced late toxicities.
      Four patients had a local recurrence after a mean delay of 10.8 months. At last
      news, 4 patients were still alive and 4/5 deaths were related to the cancer. All
      (n=3) patients who received the combination of radiotherapy - brachytherapy were
      alive and disease-free. Median overall survival was 18 months. DISCUSSION AND
      CONCLUSIONS: Primitive vaginal cancers are rare and aggressive tumours. Our
      results suggested the feasibility of the combination of radiotherapy and
      brachytherapy for elderly patients. Prospective trials remain needed to better
      define and validate the optimal strategy, especially in elderly adults.

PMID- 23969307
TI  - Five parameters you must understand to master control of your laser/light-based
      devices.
AB  - In this article, the authors review basic fundamental principles of light
      characteristics and their interaction with the target tissue. It is imperative
      for the practitioner to understand these concepts to deliver appropriate,
      efficacious, and safe phototherapeutic treatment for their patients. Once a
      diagnosis is made and a laser is chosen as a treatment tool, a basic knowledge
      and understanding of the physics and properties of light/tissue interaction is
      essential to allow practitioners to provide their patients with optimal results. 

PMID- 23969308
TI  - Decitabine can be safely reduced after achievement of best objective response in
      patients with myelodysplastic syndrome.
AB  - BACKGROUND: Decitabine is standard therapy in patients with myelodysplastic
      syndrome (MDS). Current recommendations suggest a dose of 20 mg/m(2)
      intravenously (IV) daily for 5 days every 4 weeks. However, this therapy is
      associated with frequent grade 3/4 hematologic toxicity, requiring dose delays
      and/or dose reductions (DD/DR). RESULTS: We investigated the outcomes of 122
      patients with MDS who had DD/DR of frontline decitabine therapy. Sixty-five
      patients (53%) had DR by at least 25% or DD (defined as a delay beyond 5 weeks
      between cycles). Thirty-five patients (29%) underwent DD/DR after achieving best
      objective response, 30 patients (25%) underwent DD/DR before best objective
      response, and 57 (54%) patients had no DD/DR. There was a trend for more durable
      responses in favor of patients requiring DD/DR after the achievement of best
      objective response (median not reached) (P = .161). Overall survival rates were
      significantly higher for patients who had DD/DR after best objective response
      compared with those who had DD/DR before best objective response or those with no
      DD/DR (30 vs. 22 vs. 11 months, respectively; P < .001). Progression-free
      survival (PFS) rates also trended higher for those with DD/DR after best
      objective response (median not reached) compared with those who required DD/DR
      before best objective response (median of 15 months) (P = .285). CONCLUSION:
      DD/DR may be safely accomplished once the patient has achieved best objective
      response (preferably complete remission [CR]) without impacting outcome.
      Prospective evaluation of an approach conceived of a loading dose for induction
      of a best objective response followed by a maintenance schedule is to be
      considered.

PMID- 23969309
TI  - Biological and clinical features of trisomy 21 in adult patients with acute
      myeloid leukemia.
AB  - INTRODUCTION: Trisomy 21 is frequently noted in patients with AML. In adults, +21
      has traditionally been considered an intermediate-risk cytogenetic aberration.
      PATIENTS AND METHODS: We analyzed 90 patients with newly diagnosed AML harboring
      +21. Four cytogenetic subgroups were defined based on associated cytogenetic
      abnormalities: +21 alone, +21 with favorable, +21 with intermediate, and +21 with
      unfavorable cytogenetics. RESULTS: Fifty-four percent of patients with +21 AML
      achieved a complete remission (CR) or CR with incomplete platelet recovery (CRp)
      after induction therapy with a trend toward improved CR/CRp rates in patients
      with +21 alone/+21 with favorable cytogenetics compared with patients with +21
      with intermediate/+21 with unfavorable cytogenetics (76% vs. 50%; P = .057). Time
      to progression (TTP) was 12 months (range, 5-19) and overall survival (OS) was 9
      months (range, 7-11) for the entire group. TTP was longer for patients with +21
      alone (not reached) or with +21 with favorable cytogenetics (101 months) compared
      with those with +21 with intermediate cytogenetics (2 months) or +21 with
      unfavorable cytogenetics (11 months) (P = .02). Similarly, OS was improved in
      patients with +21 with favorable cytogenetics (not reached) or +21 alone (107
      months), compared with +21 with unfavorable cytogenetics (9 months) or +21 with
      intermediate cytogenetics (8 months) (P < .001). The differences in TTP and OS
      were maintained on multivariate analysis (P = .04 and P = .001; respectively).
      CONCLUSION: Isolated +21 hitherto classified as intermediate-risk cytogenetics
      might actually behave as a favorable-risk cytogenetics in adult AML patients.

PMID- 23969310
TI  - Ancestral Myf5 gene activity in periocular connective tissue identifies a subset
      of fibro/adipogenic progenitors but does not connote a myogenic origin.
AB  - Extraocular muscles (EOM) represent a unique muscle group that controls eye
      movements and originates from head mesoderm, while the more typically studied
      body and limb muscles are somite-derived. Aiming to investigate myogenic
      progenitors (satellite cells) in EOM versus limb and diaphragm of adult mice, we
      have been using flow cytometry in combination with myogenic-specific Cre-loxP
      lineage marking for cell isolation. While analyzing cells from the EOM of mice
      that harbor Myf5(Cre)-driven GFP expression, we identified in addition to the
      expected GFP(+) myogenic cells (presumably satellite cells), a second dominant
      GFP(+) population distinguished as being Sca1(+), non-myogenic, and exhibiting a
      fibro/adipogenic potential. This unexpected population was not only unique to EOM
      compared to the other muscles but also specific to the Myf5(Cre)-driven reporter
      when compared to the MyoD(Cre) driver. Histological studies of periocular tissue
      preparations demonstrated the presence of Myf5(Cre)-driven GFP(+) cells in
      connective tissue locations adjacent to the muscle masses, including cells in the
      vasculature wall. These vasculature-associated GFP(+) cells were further
      identified as mural cells based on the presence of the specific XLacZ4 transgene.
      Unlike the EOM satellite cells that originate from a Pax3-negative lineage, these
      non-myogenic Myf5(Cre)-driven GFP(+) cells appear to be related to cells of a
      Pax3-expressing origin, presumably derived from the neural crest. In all, our
      lineage tracing based on multiple reporter lines has demonstrated that regardless
      of common ancestral expression of Myf5, there is a clear distinction between
      periocular myogenic and non-myogenic cell lineages according to their mutually
      exclusive antecedence of MyoD and Pax3 gene activity. 

PMID- 23969312
TI  - ELONGATA3 is required for shoot meristem cell cycle progression in Arabidopsis
      thaliana seedlings.
AB  - A key feature of the development of a higher plant is the continuous formation of
      new organs from the meristems. Originally patterned during embryogenesis, the
      meristems must activate cell division de novo at the time of germination, in
      order to initiate post-embryonic development. In a mutagenesis screen aimed at
      finding new players in early seedling cell division control, we identified
      ELONGATA3 (ELO3) as a key regulator of meristem cell cycle activation in
      Arabidopsis. Our results show that plants carrying a hypomorphic allele of ELO3
      fail to activate cell division in the meristems following germination, which
      leads to seedling growth arrest and lethality. Further analyses suggest that this
      is due to a failure in DNA replication, followed by cell cycle arrest, in the
      meristematic tissue. Interestingly, the meristem cell cycle arrest in elo3
      mutants, but not the later leaf developmental defects that have been linked to
      the loss of ELO3 activities, can be relieved by the addition of metabolic sugars
      in the growth medium. This finding points to a new role by which carbohydrate
      availability promotes meristem growth. Furthermore, growth arrested elo3 mutants
      suffer a partial loss of shoot meristem identity, which provides further evidence
      that cell cycle activities can influence the control of tissue identity. 

PMID- 23969311
TI  - Identification and dissection of a key enhancer mediating cranial neural crest
      specific expression of transcription factor, Ets-1.
AB  - Neural crest cells form diverse derivatives that vary according to their level of
      origin along the body axis, with only cranial neural crest cells contributing to
      facial skeleton. Interestingly, the transcription factor Ets-1 is uniquely
      expressed in cranial but not trunk neural crest, where it functions as a direct
      input into neural crest specifier genes, Sox10 and FoxD3. We have isolated and
      interrogated a cis-regulatory element, conserved between birds and mammals, that
      drives reporter expression in a manner that recapitulates that of endogenous Ets
      1 expression in the neural crest. Within a minimal Ets-1 enhancer region,
      mutation of putative binding sites for SoxE, homeobox, Ets, TFAP2 or Fox proteins
      results in loss or reduction of neural crest enhancer activity. Morpholino
      mediated loss-of-function experiments show that Sox9, Pax7, Msx1/2, Ets-1, TFAP2A
      and FoxD3, all are required for enhancer activity. In contrast, mutation of a
      putative cMyc/E-box sequence augments reporter expression, consistent with this
      being a repressor binding site. Taken together, these results uncover new inputs
      into Ets-1, revealing critical links in the cranial neural crest gene regulatory
      network. 

PMID- 23969313
TI  - Using conventional HIV tests on oral fluid.
AB  - There is need for more evaluations of non-invasive tests in order to broaden the
      reach of testing programs and to perform large scale epidemiological studies. In
      this study, three different human immunodeficiency virus (HIV) enzyme linked
      immunosorbent assays (ELISAs) and one line immunoassay were evaluated to detect
      HIV antibodies in oral fluid samples. Specimens were collected, after informed
      consent was obtained, with the Oracol (MMD, Worcester, England) device. A total
      IgG quantitation test was performed to demonstrate the quality of the sample.
      Assessment of a modified protocol of the Vironostika HIV Ag/Ab, Enzygnost Anti
      HIV 1/2 Plus Genscreen HIV-1/2 Version 2 and a line immune confirmatory assay the
      INNO-LIA HIV I/II score was done, using oral fluid specimens of 325 HIV positive
      and negative individuals. For the ELISAs, the addition of an extra internal oral
      fluid control was evaluated as well as different cut-offs, time between sampling
      and testing and the effect of drinking water just before sampling. Finally, the
      confirmatory test and some testing algorithms and combination of tests were
      discussed. The results obtained from the oral fluid specimens were compared with
      the gold standard on paired serum specimens. Firstly, there was no significant
      difference observed between the use of the kit controls and the oral fluid
      controls. New protocols and calculation of cut-offs were defined for two of the
      three ELISAs. High sensitivities and specificities were obtained with all three
      ELISAs without any statistical difference between the three tests. Secondly, no
      statistically significant difference was observed when samples were stored for
      different time periods between sampling and testing, meaning that a period of
      seven days at room temperature before testing is still acceptable. Thirdly,
      drinking water before sample collection did not interfere with the testing,
      although lower optical densities were observed. None of the positive samples were
      missed. In addition, the line immunoassay INNO-LIA HIV I/II score test is a
      promising test for confirmation of reactive oral fluid specimen, but more samples
      need to be validated in order to adapt the interpretation rules specifically for
      oral fluid specimens. Different choices/algorithms adapted for the purpose of
      testing can be proposed. In conclusion, it can be said that the commercial ELISAs
      with adapted protocol and cut-off values are suitable tools for making HIV test
      performance accessible to people. With this non-invasive sampling method, more
      eligible individuals can and will be selected for further HIV test on blood.

PMID- 23969314
TI  - Evaluation of a novel Scheimpflug-based non-contact tonometer in healthy subjects
      and patients with ocular hypertension and glaucoma.
AB  - BACKGROUND: To evaluate the agreement of intraocular pressure (IOP) and central
      corneal thickness (CCT) measurements obtained with the non-contact tonometer
      Corvis Scheimpflug Technology (Corvis ST, OCULUS, Wetzlar, Germany) versus
      Goldmann applanation tonometry (GAT) and ultrasound-based corneal pachymetry (US
      CCT). METHODS: Eye healthy participants, patients with ocular hypertension (OHT)
      and patients with open-angle glaucoma were included in this prospective study. In
      each participant, GAT, US-CCT and measurements with Corvis ST were obtained
      (Corvis-IOP and Corvis-CCT). Accuracy and repeatability were tested by
      correlation and regression analyses, Bland-Altman plots and assessment of
      intraclass correlation coefficients. RESULTS: A consecutive series of 188 right
      study eyes of 188 participants (142 eyes with glaucoma, 10 eyes with OHT and 36
      control eyes) were included in this prospective study. The mean GAT of all
      included was 14.5+/-4.8 mm Hg compared with mean Corvis-IOP of 15.4+/-5.6 mm Hg
      (Spearman's r=0.75, p<0.0001). Mean US-CCT was 544.56+/-40.0 um compared with
      Corvis-CCT of 545.2+/-46.5 um (Pearson's r=0.78, p<0.0001). Bland-Altman plots of
      all included eyes as well as subgroup analyses revealed good agreement of the IOP
      and CCT measurement techniques. High intraclass correlation coefficient values in
      17 patients with repeated measurements revealed very good repeatability (0.942
      and 0.937 for Corvis-IOP and Corvis-CCT, respectively). Corvis-IOP but not GAT
      showed a trend of dependence on CCT. CONCLUSIONS: Obtaining CCT and measuring IOP
      with the Corvis ST reveals very good repeatability and good accuracy in healthy
      subjects and patients with OHT and glaucoma when compared with standardised US
      pachymetry or GAT.

PMID- 23969315
TI  - Central serous chorioretinopathy in a 91-year-old woman.

PMID- 23969316
TI  - Imaging dynamic interactions between spliceosomal proteins and pre-mRNA in living
      cells.
AB  - The ability to observe protein dynamics in living cells is critical for the
      mechanistic understanding of highly flexible biological processes such as pre
      mRNA splicing by the spliceosome. Splicing relies on intricate RNA and protein
      networks that are repeatedly rearranged during spliceosome assembly. Here we
      describe a method based on fluorescence microscopy that has been used by our and
      other laboratories to study interaction of spliceosomal proteins with nascent pre
      mRNA in living cells. The method involves co-expressing in mammalian cells the
      target pre-mRNA labeled with one color, and the spliceosomal protein tagged with
      another color. The diffusion coefficient of the protein as well as its
      association and dissociation rates with the pre-mRNA are estimated by
      fluorescence recovery after photobleaching (FRAP) or photoactivation. 

PMID- 23969318
TI  - PCR-based Methodologies Used to Detect and Differentiate the Burkholderia
      pseudomallei complex: B. pseudomallei, B. mallei, and B. thailandensis.
AB  - Methods for the rapid detection and differentiation of the Burkholderia
      pseudomallei complex comprising B. pseudomallei, B. mallei, and B. thailandensis,
      have been the topic of recent research due to the high degree of phenotypic and
      genotypic similarities of these species. B. pseudomallei and B. mallei are
      recognized by the CDC as tier 1 select agents. The high mortality rates of
      glanders and melioidosis, their potential use as bioweapons, and their low
      infectious dose, necessitate the need for rapid and accurate detection methods.
      Although B. thailandensis is generally avirulent in mammals, this species
      displays very similar phenotypic characteristics to that of B. pseudomallei.
      Optimal identification of these species remains problematic, due to the
      difficulty in developing a sensitive, selective, and accurate assay. The
      development of PCR technologies has revolutionized diagnostic testing and these
      detection methods have become popular due to their speed, sensitivity, and
      accuracy. The purpose of this review is to provide a comprehensive overview and
      evaluation of the advancements in PCR-based detection and differentiation
      methodologies for the B. pseudomallei complex, and examine their potential uses
      in diagnostic and environmental testing. 

PMID- 23969319
TI  - Successfully treated abdominal pregnancy causing hemoperitoneum using combined
      surgical and systemic methotrexate therapy: a case report and review of cases
      treated at Kyushu University Hospital.
AB  - Abdominal pregnancy is a rare condition that accounts for only 1% of all ectopic
      pregnancies but results in high maternal morbidity and mortality. We present a
      case of abdominal pregnancy with massive peritoneal bleeding successfully treated
      using systemic methotrexate (MTX). A 34-year-old woman with amenorrhea for 8
      weeks and a positive pregnancy test was referred for evaluation of ectopic
      pregnancy. Transvaginal ultrasonographic scan showed a gestational sac measuring
      25 mm in diameter containing a viable embryo in the cul-de-sac and a considerable
      amount of free fluid in the patient's lower abdomen and pelvis. Laboratory
      parameters showed that her hemoglobin concentration was 5.8 g/dl and serum human
      chorionic gonadotropin concentration was 13,195 mIU/ml. Emergency surgery
      revealed an abdominal pregnancy in the cul-de-sac and a massive intra-abdominal
      hemorrhage. After a hemostasis procedure, the patient was successfully treated
      using systemic MTX. We also present the review of abdominal pregnancy cases
      treated using systemic MTX at our institution over 10 years. Systemic MTX
      treatment for abdominal pregnancy is safe and effective and makes it possible to
      avoid the risk of excessive bleeding by surgical resection of the implantation
      site. 

PMID- 23969321
TI  - Beneficial effects of fresh and fermented kimchi in prediabetic individuals.
AB  - BACKGROUND: With the increased incidence of diabetes mellitus, the importance of
      early intervention in prediabetes has been emphasized. We previously reported
      that fermented kimchi, a traditional Korean food, reduced body weight and
      improved metabolic factors in overweight participants. We hypothesized that
      kimchi and its fermented form would have beneficial effects on glucose metabolism
      in patients with prediabetes. METHODS: A total of 21 participants with
      prediabetes were enrolled. During the first 8 weeks, they consumed either fresh
      (1-day-old) or fermented (10-day-old) kimchi. After a 4-week washout period, they
      switched to the other type of kimchi for the next 8 weeks. RESULTS: Consumption
      of both types of kimchi significantly decreased body weight, body mass index, and
      waist circumference. Fermented kimchi decreased insulin resistance, and increased
      insulin sensitivity, QUICKI and disposition index values (p = 0.004 and 0.028,
      respectively). Systolic and diastolic blood pressure (BP) decreased significantly
      in the fermented kimchi group. The percentages of participants who showed
      improved glucose tolerance were 9.5 and 33.3% in the fresh and fermented kimchi
      groups, respectively. CONCLUSIONS: Consumption of kimchi had beneficial effects
      on glucose metabolism-related and anthropometric factors in participants with
      prediabetes. Fermented kimchi had additional effects on BP and insulin
      resistance/sensitivity. The percentage of participants who showed improvement in
      glucose tolerance was high in the fermented kimchi group.

PMID- 23969322
TI  - Helium atom scattering investigation of the Sb(111) surface.
AB  - The Sb(111) surface was studied with helium atom scattering (HAS). Elastic HAS at
      different energies of the incident helium beam (15.3, 21.9, 28.4 meV) was applied
      for structural investigations. The lattice constants derived from the positions
      of the observed diffraction peaks up to third order were found to be in perfect
      agreement with previous structure determinations of Sb(111). The observed
      diffraction patterns with clear peaks up to second order were used to model the
      electronic surface corrugation with the GR method. As an estimation for the
      attractive part of the interaction potential a well depth of (4.0 +/- 0.5) meV
      was found. Best fit results were obtained with a corrugation height of 12-13% of
      the lattice constant, which is rather large compared to other surfaces with
      metallic character. Intensity measurements of the specular peak as a function of
      incident energy were analysed to determine the distribution of terraces on the
      surface. The results show a quite flat Sb(111) surface and a step height of 3.81
      A of the remaining terraces.

PMID- 23969317
TI  - Integrating virtual and biochemical screening for protein tyrosine phosphatase
      inhibitor discovery.
AB  - Protein tyrosine phosphatases (PTPs) represent an important class of enzymes that
      mediate signal transduction and control diverse aspects of cell behavior. The
      importance of their activity is exemplified by their significant contribution to
      disease etiology with over half of all human PTP genes implicated in at least one
      disease. Small molecule inhibitors targeting individual PTPs are important
      biological tools, and are needed to fully characterize the function of these
      enzymes. Moreover, potent and selective PTP inhibitors hold the promise to
      transform the treatment of many diseases. While numerous methods exist to develop
      PTP-directed small molecules, we have found that complimentary use of both
      virtual (in silico) and biochemical (in vitro) screening approaches expedite
      compound identification and drug development. Here, we summarize methods
      pertinent to our work and others. Focusing on specific challenges and successes
      we have experienced, we discuss the considerable caution that must be taken to
      avoid enrichment of inhibitors that function by non-selective oxidation. We also
      discuss the utility of using "open" PTP structures to identify active-site
      directed compounds, a rather unconventional choice for virtual screening. When
      integrated closely, virtual and biochemical screening can be used in a productive
      workflow to identify small molecules targeting PTPs. 

PMID- 23969323
TI  - Pediatric cervical intraosseous schwannoma.
AB  - Intraosseous schwannoma of the spine is an extremely rare tumor, with only 18
      cases reported so far in the literature. We describe the 1st case of intraosseous
      schwannoma in the pediatric age group, which was treated successfully, and we
      review the pertinent literature. 

PMID- 23969324
TI  - Guidelines of diagnostics and treatment of acute left-sided colonic
      diverticulitis.
AB  - BACKGROUND: The incidence of acute left-sided colonic diverticulitis (ACD) is
      increasing in the Western world. To improve the quality of patient care, a
      guideline for diagnosis and treatment of diverticulitis is needed. METHODS: A
      multidisciplinary working group, representing experts of relevant specialties,
      was involved in the guideline development. A systematic literature search was
      conducted to collect scientific evidence on epidemiology, classification,
      diagnostics and treatment of diverticulitis. Literature was assessed using the
      classification system according to an evidence-based guideline development
      method, and levels of evidence of the conclusions were assigned to each topic.
      Final recommendations were given, taking into account the level of evidence of
      the conclusions and other relevant considerations such as patient preferences,
      costs and availability of facilities. RESULTS: The natural history of
      diverticulitis is usually mild and treatment is mostly conservative. Although
      younger patients have a higher risk of recurrent disease, a higher risk of
      complications compared to older patients was not found. In general, the clinical
      diagnosis of ACD is not accurate enough and therefore imaging is indicated. The
      triad of pain in the lower left abdomen on physical examination, the absence of
      vomiting and a C-reactive protein >50 mg/l has a high predictive value to
      diagnose ACD. If this triad is present and there are no signs of complicated
      disease, patients may be withheld from further imaging. If imaging is indicated,
      conditional computed tomography, only after a negative or inconclusive
      ultrasound, gives the best results. There is no indication for routine endoscopic
      examination after an episode of diverticulitis. There is no evidence for the
      routine administration of antibiotics in patients with clinically mild
      uncomplicated diverticulitis. Treatment of pericolic or pelvic abscesses can
      initially be treated with antibiotic therapy or combined with percutaneous
      drainage. If this treatment fails, surgical drainage is required. Patients with a
      perforated ACD resulting in peritonitis should undergo an emergency operation.
      There is an ongoing debate about the optimal surgical strategy. CONCLUSION:
      Scientific evidence is scarce for some aspects of ACD treatment (e.g. natural
      history of ACD, ACD in special patient groups, prevention of ACD, treatment of
      uncomplicated ACD and medical treatment of recurrent ACD), leading to treatment
      being guided by the surgeon's personal preference. Other aspects of the
      management of patients with ACD have been more thoroughly researched (e.g.
      imaging techniques, treatment of complicated ACD and elective surgery of ACD).
      This guideline of the diagnostics and treatment of ACD can be used as a reference
      for clinicians who treat patients with ACD.

PMID- 23969325
TI  - Faster, higher, stronger? Evidence for formulation and efficacy for ibuprofen in
      acute pain.
AB  - A Cochrane review of ibuprofen in acute pain suggested that rapidly absorbed
      formulations of salts, or features to speed absorption, provided better analgesia
      than standard ibuprofen as the free acid. We examined several lines of evidence
      to investigate what benefit derived from fast-acting formulations. A systematic
      review of the kinetics of oral ibuprofen (30 studies, 1015 subjects) showed that
      median maximum plasma concentrations of fast-acting formulations occurred before
      50 min (29-35 min for arginine, lysine, and sodium salts) compared with 90 min
      for standard formulations. An updated analysis of clinical trials (over 10,000
      patients) showed that fast-acting formulations produced significantly better
      analgesia over 6h and fewer remedications than standard formulations in both
      indirect and direct comparisons. In dental studies, 200-mg fast-acting ibuprofen
      (number needed to treat 2.1; 95% confidence interval 1.9-2.4) was as effective as
      400 mg standard ibuprofen (number needed to treat 2.4; 95% confidence interval
      2.2-2.5), with faster onset of analgesia. Individual patient data analysis in
      dental pain demonstrated a strong correlation between more rapid reduction of
      pain intensity over 0-60 min and better pain relief over 0-6h. Rapid initial
      reduction of pain intensity was also linked with reduced need for remedication.
      Fast-acting formulations of ibuprofen demonstrated more rapid absorption, faster
      initial pain reduction, good overall analgesia in more patients at the same dose,
      and probably longer-lasting analgesia, but with no higher rate of patients
      reporting adverse events. Achieving a better analgesic effect with fast-acting
      nonsteroidal anti-inflammatory drug formulations has important implications for
      safety. Formulation chemistry is of potential importance for analgesics.

PMID- 23969326
TI  - Prognostic value of coping strategies in a community-based sample of persons with
      chronic symptomatic knee osteoarthritis.
AB  - Radiographic knee osteoarthritis (OA) is a highly prevalent condition that has
      been the focus of a number of studies identifying factors that are prognostic of
      continued or worsening pain and function. Although prior prognostic studies have
      identified a number of demographic, physical, and psychological factors that are
      predictive of outcome, minimal focus has been placed on pain coping skills as
      prognostic factors, despite cross-sectional evidence suggesting that pain coping
      skills are associated with pain and function in knee OA. The present study
      reports on the use of pain coping skills as prognostic factors for changes in
      pain and/or function over a 1-year period. Participants were drawn from the
      Osteoarthritis Initiative, a prospective longitudinal cohort study of persons
      recruited from the community who either had knee OA or were at high risk for
      developing knee OA. Data from the Coping Strategies Questionnaire were compared
      against 1-year change in pain, function, or both, using established criteria for
      defining whether the patient got better, worse, or stayed the same over the 1
      year period. Results revealed a significant effect for praying/hoping, increased
      behavioral activities, and pain catastrophizing as prognostic of pain outcomes;
      ignoring pain and praying/hoping were prognostic of function outcomes; and
      increased behavioral activities and pain catastrophizing were prognostic of a
      combined pain and function outcome. The findings provide important new evidence
      regarding the potential clinical relevance of a number of pain coping responses
      hypothesized to influence future pain and function in persons with arthritis. 

PMID- 23969327
TI  - Risk factors for developing prolonged grief during bereavement in family carers
      of cancer patients in palliative care: a longitudinal study.
AB  - CONTEXT: Family carers of palliative care patients report high levels of
      psychological distress throughout the caregiving phase and during bereavement.
      Palliative care providers are required to provide psychosocial support to family
      carers; however, determining which carers are more likely to develop prolonged
      grief (PG) is currently unclear. OBJECTIVES: To ascertain whether family carers
      reporting high levels of PG symptoms and those who develop PG disorder (PGD) by
      six and 13 months postdeath can be predicted from predeath information. METHODS:
      A longitudinal study of 301 carers of patients receiving palliative care was
      conducted across three palliative care services. Data were collected on entry to
      palliative care (T1) on a variety of sociodemographic variables, carer-related
      factors, and psychological distress measures. The measures of psychological
      distress were then readministered at six (T2; n=167) and 13 months postdeath (T3;
      n=143). RESULTS: The PG symptoms at T1 were a strong predictor of both PG
      symptoms and PGD at T2 and T3. Greater bereavement dependency, a spousal
      relationship to the patient, greater impact of caring on schedule, poor family
      functioning, and low levels of optimism also were risk factors for PG symptoms.
      CONCLUSION: Screening family carers on entry to palliative care seems to be the
      most effective way of identifying who has a higher risk of developing PG. We
      recommend screening carers six months after the death of their relative to
      identify most carers with PG.

PMID- 23969328
TI  - A hospital-based palliative care service for patients with advanced organ failure
      in sub-Saharan Africa reduces admissions and increases home death rates.
AB  - CONTEXT: Despite emerging data of cost savings under palliative care in various
      regions, no such data have been generated in response to the high burden of
      terminal illness in Africa. OBJECTIVES: This evaluation of a novel hospital-based
      palliative care service for patients with advanced organ failure in urban South
      Africa aimed to determine whether the service reduces admissions and increases
      home death rates compared with the same fixed time period of standard hospital
      care. METHODS: Data on admissions and place of death were extracted from routine
      hospital activity records for a fixed period before death, using standard patient
      daily expense rates. Data from the first 56 consecutive deaths under the new
      service (intervention group) were compared with 48 consecutive deaths among
      patients immediately before the new service (historical controls). RESULTS: Among
      the intervention and control patients, 40 of 56 (71.4%) and 47 of 48 (97.9%),
      respectively, had at least one admission (P < 0.001). The mean number of
      admissions for the intervention and control groups was 1.39 and 1.98,
      respectively (P < 0.001). The mean total number of days spent admitted for
      intervention and control groups was 4.52 and 9.3 days, respectively (P < 0.001).
      For the intervention and control patients, a total of 253 and 447 admission days
      were recorded, respectively, with formal costs of $587 and $1209, respectively.
      For the intervention and control groups, home death was achieved by 33 of 56
      (58.9%) and nine of 48 (18.8%), respectively (P <= 0.001). CONCLUSION: These data
      demonstrate that an outpatient hospital-based service reduced admissions and
      improved the rate of home deaths and offers a feasible and cost-effective model
      for such settings.

PMID- 23969329
TI  - The circadian clock and cell cycle: interconnected biological circuits.
AB  - The circadian clock governs biological timekeeping on a systemic level, helping
      to regulate and maintain physiological processes, including endocrine and
      metabolic pathways with a periodicity of 24-hours. Disruption within the
      circadian clock machinery has been linked to numerous pathological conditions,
      including cancer, suggesting that clock-dependent regulation of the cell cycle is
      an essential control mechanism. This review will highlight recent advances on the
      'gating' controls of the circadian clock at various checkpoints of the cell cycle
      and also how the cell cycle can influence biological rhythms. The reciprocal
      influence that the circadian clock and cell cycle exert on each other suggests
      that these intertwined biological circuits are essential and multiple
      regulatory/control steps have been instated to ensure proper timekeeping. 

PMID- 23969331
TI  - A new ionic liquid-water-organic solvent three phase microextraction for
      simultaneous preconcentration flavonoids and anthraquinones from traditional
      Chinese prescription.
AB  - A novel technique, ionic liquid-water-organic solvent three phase microextraction
      (ILWOS-3p-ME) was developed and introduced for simultaneous preconcentration and
      determination of flavonoids and anthraquinones in Chinese herbal formula and its
      preparations. This technique was performed in one step by using a syringe. High
      performance liquid chromatography with an UV-detector (HPLC/UV) was subsequently
      conducted. Two solvents with different densities (organic solvent and ionic
      liquid with densities less than and higher than water, respectively) were
      separately placed in a syringe, which was used as an extraction device. A cloudy
      emulsion was formed by manually shaking the syringe. The mixture was allowed to
      stand for several minutes; afterward, the emulsion readily separated into three
      phases: an upper organic solvent extraction phase; a middle aqueous sample phase;
      and a lower ionic liquid extraction phase. Both the upper and lower layers were
      transferred to a small Eppendorf (EP) tube. Conducting ILWOS-3P-ME with HPLC/UV,
      we simultaneously determined the bioactive components of flavonoids and
      anthraquinones in traditional Chinese medicine. ILWOS-3P-ME is a simple, rapid,
      practical, and effective method to extract and preconcentrate of different types
      of trace bioactive components from traditional Chinese medicine simultaneously. 

PMID- 23969330
TI  - Forced degradation and impurity profiling: recent trends in analytical
      perspectives.
AB  - This review describes an epigrammatic impression of the recent trends in
      analytical perspectives of degradation and impurities profiling of
      pharmaceuticals including active pharmaceutical ingredient (API) as well as drug
      products during 2008-2012. These recent trends in forced degradation and impurity
      profiling were discussed on the head of year of publication; columns, matrix (API
      and dosage forms) and type of elution in chromatography (isocratic and gradient);
      therapeutic categories of the drug which were used for analysis. It focuses
      distinctly on comprehensive update of various analytical methods including
      hyphenated techniques for the identification and quantification of thresholds of
      impurities and degradants in different pharmaceutical matrices. 

PMID- 23969332
TI  - Beclomethasone dipropionate and formoterol reduce oxidative/nitrosative stress
      generated by cigarette smoke extracts and IL-17A in human bronchial epithelial
      cells.
AB  - Interleukin-17A (IL-17A), cigarette smoke and oxidative/nitrosative stress are
      involved in inflammatory airway diseases, and the mechanisms behind these
      processes are still poorly understood. We investigated whether recombinant human
      IL-17A (rhIL-17A), in combination with cigarette smoke extracts (CSE), increases
      the levels of inducibile nitric oxide synthase (iNOS), reactive oxygen species,
      nitrotyrosine (NT) and the activation of signal transducer and activator of
      transcription 1 (STAT-1) in normal human bronchial epithelial cells (16HBE). The
      effect of beclomethasone dipropionate (BDP), formoterol and their combination was
      also evaluated. We demonstrated that rhIL-17A or CSE alone increases iNOS
      expression, reactive oxygen species and NT production and STAT-1 downstream
      signalling activation in terms of STAT-1ser727 and STAT-1tyr701 phosphorylation.
      The combination of both stimuli further increased iNOS, ROS, NT and STAT-1ser727
      phosphorylation. The silencing of STAT-1 expression partially reduced the levels
      of iNOS, reactive oxygen species and NT generated by rhIL-17A and inhibited the
      effect of CSE alone in 16HBE cells. The treatment of the cells with the MEK1/2
      inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis (o-aminophenylmercapto
      butadiene) abolished the expression of iNOS and STAT-1ser727 phosphorylation
      generated by rhIL-17A. 16HBE treated with BDP or formoterol alone partially
      suppressed the effect of IL-17A or CSE on ROS, NT, and STAT-1 activation.
      Furthermore the use of the drugs in combination showed an additive effect in
      16HBE. Our findings demonstrate that IL-17A increases oxidative/nitrosative
      markers, likely via ERK1/2 downstream signalling and STAT-1 pathway activation in
      human bronchial epithelial cells. BDP and formoterol treatment reduces this
      effect showing an additive effect used in combination. 

PMID- 23969333
TI  - Epidermal nevus and ameloblastoma: a rare association.
AB  - Epidermal nevi are clinical manifestations of a malformation affecting the
      embryonic ectoderm. They appear as linear verrucous lesions and are more often
      located in the skin of the trunk or the extremities. Rarely, verrucous lesions
      affect the oral mucosa. Epidermal nevi can be a component of epidermal nevus
      syndrome (ENS), which is characterized by malformations involving several organs,
      such as the central nervous system. ENS is rarely associated with other solid
      tumors. We present the case of a patient affected by ENS who developed maxillary
      and mandibular ameloblastomas. Epidermal nevi were located in the left middle and
      lower third of the face and in the left cervical region, whereas the
      ameloblastomas arose within the left maxillary mucosa and within the left
      mandibular ramus. Features of the syndrome are described and the relevant
      literature is reviewed. 

PMID- 23969334
TI  - Effect of mouth cleaning with hinokitiol-containing gel on oral malodor: a
      randomized, open-label pilot study.
AB  - AIM: The aim of the study was to evaluate the effect of mouth cleaning with
      hinokitiol-containing gel on oral malodor. METHODS: An open-label, randomized,
      controlled trial was conducted to assess oral malodor and clinical parameters
      related to oral malodor before and after mouth cleaning with hinokitiol
      containing gel (n = 9) or with gel not including hinokitiol (n = 9). Mouth
      cleaning included the teeth, gingiva, and tongue and was carried out 3 times per
      day for 4 weeks. RESULTS: Organoleptic test (OLT) scores (P = .021), levels of
      hydrogen sulfide (P = .008) and methyl mercaptan (P = .020), frequency of
      bleeding on probing, average probing pocket depth, and plaque index significantly
      improved in the group using hinokitiol. In contrast, only the OLT score (P =
      .031) significantly improved in the control group after the treatment regimen.
      CONCLUSION: Mouth cleaning with hinokitiol-containing gel may be effective for
      reduction of oral malodor.

PMID- 23969335
TI  - Under-recognized: inflammatory trigeminal neuropathy.

PMID- 23969336
TI  - Laparoscopy versus laparotomy in the management of ectopic pregnancy with massive
      hemoperitoneum.
AB  - OBJECTIVE: To compare the safety and feasibility of operative laparoscopy versus
      laparotomy in women with ruptured ectopic pregnancy and massive hemoperitoneum.
      METHODS: In a retrospective cohort study at a university-affiliated medical
      center, records of women with ruptured ectopic pregnancy and massive
      hemoperitoneum (>800mL) were reviewed. RESULTS: Sixty women were diagnosed with
      ruptured ectopic pregnancy and massive hemoperitoneum: 48 underwent emergency
      laparoscopy; 12 underwent emergency laparotomy. There was no difference in
      hemodynamic status at presentation between the groups. Median operating time was
      significantly shorter in the laparoscopy group (50minutes [range, 43-63minutes]
      vs 60minutes [range, 60-72minutes]; P=0.01). Median intra-abdominal blood loss
      was significantly greater in the laparotomy group (1500mL [range, 1400-2000mL] vs
      1000mL [range, 800-1200mL]; P=0.002). There was no difference between the groups
      regarding treatment with blood products, perioperative complications, and
      hospitalization period. CONCLUSION: In patients with ruptured ectopic pregnancy
      and massive hemoperitoneum, laparoscopy is feasible and safe, with significantly
      shorter operating times compared with laparotomy. While the mode of surgery
      should be based on the surgeon's experience and preference, the significantly
      lower hemoperitoneum volume associated with laparoscopy may be a reflection of
      shorter operating times and quicker hemorrhage control.

PMID- 23969337
TI  - Maternal deaths attributable to hypertensive disorders in a tertiary hospital in
      Ghana.
AB  - OBJECTIVE: To determine the contribution of hypertensive disorders of pregnancy
      to maternal deaths at Korle Bu Teaching Hospital (KBTH) in Accra, Ghana. METHODS:
      The retrospective descriptive study conducted at KBTH during 2010-2011 involved a
      comprehensive review of all maternal deaths attributable to hypertensive
      disorders. RESULTS: There were 21 385 deliveries, 21742 live births, and 199
      maternal deaths, resulting in a maternal mortality ratio of 915.3 per 100000 live
      births. In total, 63 (31.7%) maternal deaths were attributable to hypertensive
      disorders with a case fatality rate of 3.9%. The incidence of hypertensive
      disorders of pregnancy was 7.6%. Hypertensive disorders were the most common
      direct cause of maternal death followed by obstetric hemorrhage (26.6%), unsafe
      abortion (11.1%), and puerperal sepsis (3.5%). Most (38.1%) hypertension-related
      maternal deaths occurred within 24hours of admission and the majority (79.4%) had
      been referred. Eclampsia was the leading immediate cause of hypertension-related
      death (23.8%), followed by acute renal failure (20.6%), intracerebral hemorrhage
      (15.9%), and pulmonary edema (12.7%). CONCLUSION: Hypertensive diseases are the
      leading cause of maternal death at KBTH, having overtaken obstetric hemorrhage,
      with eclampsia, acute renal failure, intracerebral hemorrhage, and pulmonary
      edema representing the major immediate causes of hypertension-related maternal
      death.

PMID- 23969338
TI  - Knockdown of PSMB7 induces autophagy in cardiomyocyte cultures: possible role in
      endoplasmic reticulum stress.
AB  - Proteasomal and autophagic pathways of protein degradation are two essential,
      endoplasmic reticulum (ER)-associated proteolytic systems involved in the ER
      stress response. The functional interaction between them has been shown by
      proteasome pharmacological inhibition. However, little data have been found
      concerning autophagy induction using an RNA interference approach due to the
      multisubunit composition of proteolytic systems. We suggested that silencing of
      single proteasome subunits can induce massive autophagy. Psmb7-specific small
      interference RNA added to isolated cardiomyocytes significantly affected mRNA
      expression of essential ER stress marker proteins, including DDIT3/CHOP and
      HSPA5/GRP78. mRNA expression of the key autophagy regulator MTOR was also
      increased. These findings were confirmed by single-cell reverse transcription
      real-time PCR on individual monodansylcadaverine (MDC)-labeled cardiomyocytes.
      RNA interference that decreased the levels of non-catalytic PSMB7 subunits of the
      proteasome had no influence on chymotrypsin- and trypsin-like activities, but
      significantly decreased peptidyl-glutamyl peptide-hydrolyzing activity.
      Immunohistochemical analysis showed increased levels of LC3-marked vacuoles in
      the cytoplasm of Psmb7-knockdown cells, and MDC staining showed significantly
      increased numbers of neonatal cardiomyocytes with autophagic vacuoles. After
      anoxia-reoxygenation, the number of cells with signs of autophagy after Psmb7
      gene silencing was higher. Our results indicate that Psmb7 knockdown induces ER
      stress and autophagy in cardiomyocytes, which may be a useful approach to
      activate specific autophagy. 

PMID- 23969339
TI  - Long insular artery infarction: characteristics of a previously unrecognized
      entity.
AB  - BACKGROUND AND PURPOSE: The infarctions arising in the long insular arteries of
      the M2 segment have been poorly described in the past. The purpose of this study
      was to investigate the incidence, clinical characteristics, and pathogenesis of
      long insular artery infarcts. MATERIALS AND METHODS: Patients with acute isolated
      infarcts in territories of the long insular arteries and lenticulostriate
      arteries were retrospectively reviewed. The long insular artery territory was
      defined as the area above the lenticulostriate artery territory at the level of
      centrum semiovale. On the coronal section, it lies between the tip of the
      anterior horn and the top of the superior limb of the insular cleft. Clinical
      features and prevalence of embolic sources were compared between the 2 groups.
      RESULTS: Of 356 consecutive patients with acute ischemic stroke, 8 (2.2%) had a
      long insular artery infarct (long insular artery group) and 50 (14.0%) had a
      lenticulostriate artery infarct (lenticulostriate artery group). There were no
      differences in age, sex, prevalence of risk factors, neurologic deficit, or
      incidence of lacunar syndromes between these groups. Abrupt onset was more common
      in the long insular artery than in the lenticulostriate artery group (P = .004).
      The prevalence of embolic high-risk sources (eg, atrial fibrillation) was not
      significantly different between these groups, but the combined prevalence of all
      embolic sources, including moderate-risk sources, was significantly higher in the
      long insular artery group (P = .048). CONCLUSIONS: Isolated infarction caused by
      long insular artery occlusion is not rare. Abrupt onset is more common for long
      insular artery infarction, and this finding could be attributed to the higher
      incidence of an embolic etiology as the pathogenesis of infarction.

PMID- 23969340
TI  - Combination therapy consisting of ethanol and radiofrequency ablation for
      predominantly cystic thyroid nodules.
AB  - SUMMARY: Predominantly cystic thyroid nodules are often aspirated before
      radiofrequency ablation to enhance its efficacy; however internal bleeding during
      the aspiration is a problem. We evaluated the feasibility and safety of ethanol
      ablation to control internal bleeding that occurred during preparatory
      aspiration. Between September 2010 and August 2011, 11 of 40 predominantly cystic
      nodules bled internally during fluid aspiration before radiofrequency ablation.
      To control the bleeding, 99% ethanol was injected. The efficacy of ethanol in
      controlling bleeding, final nodule volume and complications were assessed.
      Control of the bleeding by ethanol ablation and subsequent radiofrequency
      ablation was feasible in all patients. Ninety-one percent (10/11) could be
      treated in 1 session. The mean nodule volume dropped from 17.1 to 4.3 mL (P <
      .018). There were no major complications. Ethanol ablation and radiofrequency
      ablation combination therapy is a feasible and safe technique for treating
      predominantly cystic thyroid nodules that exhibit internal bleeding during
      preparatory aspiration.

PMID- 23969341
TI  - Review of transcranial Doppler ultrasound to detect microemboli during orthopedic
      surgery.
AB  - Transcranial Doppler ultrasonography has been used to detect microemboli in the
      middle cerebral artery during orthopedic surgery. We conducted a comprehensive
      systematic literature review of transcranial Doppler ultrasonography in
      orthopedic surgery to evaluate its status in this setting. Fourteen studies were
      selected for qualitative analysis. The highest number of patients studied was 45;
      emboli were detected in all studies, occurring in 20%-100% of patients. Most
      embolic counts were below 10, but some high counts were noted. No study reported
      all the technical parameters of the transcranial Doppler ultrasonography. All
      studies assessed neurologic status, and 6 studies evaluated cognitive function
      postoperatively. No study identified an association between postoperative
      cognitive function and embolic count. Six studies sought the presence of right-to
      left shunts.

PMID- 23969342
TI  - Improved quality and diagnostic confidence achieved by use of dose-reduced
      gadolinium blood-pool agents for time-resolved intracranial MR angiography.
AB  - BACKGROUND AND PURPOSE: Time-resolved MRA with the use of bolus injection of
      paramagnetic agents has proved valuable in neurovascular imaging. Standard
      contrast agents have limited blood-pool residence times, motivating the
      development of highly protein-bound blood-pool agents with greater relaxivity and
      longer intravascular residence, affording improved image quality at lesser doses.
      This study represents the first comparison of blood-pool agents to standard
      agents in time-resolved cerebral MRA. MATERIALS AND METHODS: One hundred datasets
      were acquired at 1.5 T by use of a standardized, time-resolved MRA protocol.
      Patients received either unit dosing of a standard extracellular agent at 0.1
      mmol/kg or a blood-pool agent at 0.03 mmol/kg. Peak arterial and venous
      enhancement phases were identified and subsequently scored qualitatively by use
      of a 4-point Likert scale, with attention to 6 vascular segments: 1) intracranial
      ICA; 2) MCA M1; 3) MCA M2; 4) MCA M3; 5) deep cerebral veins; and 6) dural venous
      sinuses. RESULTS: Fifty MR angiographies were acquired with each agent. No
      significant differences were found between agents in generation of uncontaminated
      arteriograms. Blood-pool agents, at 67% dose reduction, were of significantly
      greater quality across most vascular segments, including ICA (P = .019), M2 (P =
      .003), and M3 (P < .01). Superiority in the M1 segment approached significance (P
      = .059). Significantly better venographic quality was noted for deep venous
      structures (P = .016) with the use of blood-pool agents. CONCLUSIONS: Blood-pool
      agents provide superior demonstration of most intracranial vessels in time
      resolved MRA compared with standard agents, at reduced doses. The greater
      relaxation enhancement and more favorable dosing profile make blood-pool agents
      superior to standard agents for use in cerebral time-resolved MRA.

PMID- 23969343
TI  - Histogram analysis of intravoxel incoherent motion for differentiating recurrent
      tumor from treatment effect in patients with glioblastoma: initial clinical
      experience.
AB  - BACKGROUND AND PURPOSE: Intravoxel incoherent motion can simultaneously measure
      diffusion and perfusion characteristics. Our aim was to determine whether the
      perfusion and diffusion parameters derived from intravoxel incoherent motion
      could act as imaging biomarkers for distinguishing recurrent tumor from treatment
      effect in patients with glioblastoma. MATERIALS AND METHODS: Fifty-one patients
      with pathologically confirmed recurrent tumor (n = 31) or treatment effect (n =
      20) were assessed by means of intravoxel incoherent motion MR imaging. The
      histogram cutoffs of the 90th percentiles for perfusion and normalized CBV and
      the 10th percentiles for diffusion and ADC were calculated and correlated with
      the final pathology results. A leave-one-out cross-validation was used to
      evaluate the diagnostic performance of our classifiers. RESULTS: The mean 90th
      percentile for perfusion was significantly higher in the recurrent tumor group
      (0.084 +/- 0.020) than in the treatment effect group (0.040 +/- 0.010) (P <
      .001). The 90th percentile for perfusion provided a smaller number of patients
      within an overlap zone in which misclassifications can occur, compared with the
      90th percentile for normalized CBV. The mean 10th percentile for diffusion was
      significantly lower in the recurrent tumor group than in the treatment effect
      group (P = .006). Receiver operating characteristic curve analyses showed the
      90th percentile for perfusion to be a significant predictor for differentiation,
      with a sensitivity of 87.1% and a specificity of 95.0%. There was a significant
      positive correlation between the 90th percentiles for perfusion and normalized
      CBV (r = 0.674; P < .001). CONCLUSIONS: A histogram analysis of intravoxel
      incoherent motion parameters can be used as a noninvasive imaging biomarker for
      differentiating recurrent tumor from treatment effect in patients with
      glioblastoma.

PMID- 23969344
TI  - CT angiography findings in carotid blowout syndrome and its role as a predictor
      of 1-year survival.
AB  - BACKGROUND AND PURPOSE: Carotid blowout is a serious late complication of prior
      treatment of advanced head and neck cancer. We evaluate the efficacy of CTA in
      the diagnosis of impending carotid blowout syndrome in patients with head and
      neck cancer, and its capability to predict clinical outcome. MATERIALS AND
      METHODS: The clinical data of 29 patients with impending carotid blowout who
      underwent CTA were collected and analyzed. Imaging signs included tissue
      necrosis, exposed artery, viable perivascular tumor, pseudoaneurysm, and contrast
      extravasation. DSA was obtained in 20 patients. One-year outcomes were compared
      based on management. RESULTS: The most common CTA finding was necrosis (94%),
      followed by exposed artery (73%), viable tumor (67%), pseudoaneurysm (58%), and
      contrast extravasation (30%). Exposed artery, pseudoaneurysm, and contrast
      extravasation were the 3 CTA findings related to outcomes. All of the
      pseudoaneurysm and contrast extravasation cases were associated with an exposed
      artery. An exposed artery was the most important prognostic predictor and could
      not be diagnosed on DSA. Patients without the 3 findings on CTA (group 1) had the
      best survival rate at 1-year follow-up, followed by patients with the 3 findings
      treated immediately by permanent artery occlusion (group 2). Patients with the 3
      findings who had no immediate treatment (group 3) had the worst outcomes (P <
      .001 in group 1 vs group 3 and group 2 vs group 3; P = .056 group 1 vs group 2).
      CONCLUSIONS: CTA, with its ability to diagnose an exposed artery compared with
      DSA, may offer important management and prognostic information in patients with
      impending carotid blowout.

PMID- 23969345
TI  - CT and MRI of pediatric skull lesions with fluid-fluid levels.
AB  - Fluid-fluid levels can occur whenever different fluid densities are contained
      within a cystic or compartmentalized lesion, usually related to the evolution of
      hematoma or necrosis. Review of the literature demonstrated that throughout the
      skeletal system, the most common etiology for fluid-fluid levels is aneurysmal
      bone cyst, but there are no dedicated studies of the pediatric calvaria, to our
      knowledge. In this report, we present clinicopathologic characteristics and CT
      and MR imaging of 11 patients with pediatric skull mass lesions demonstrating
      fluid-fluid levels. MR imaging demonstrated more fluid-fluid levels compared with
      CT in all cases. The etiologies of skull lesions with fluid-fluid levels were
      Langerhans cell histiocytosis in 4 (36.6%), aneurysmal bone cysts in 3 (27.2%),
      cephalohematoma in 3 (27.2%), and metastatic neuroblastoma in 1 (9%).
      Radiologists should be aware of the other etiologies of calvarial lesions with
      fluid-fluid levels in the pediatric skull.

PMID- 23969346
TI  - Economic conditions and health behaviours during the 'Great Recession'.
AB  - BACKGROUND: The adoption of healthier behaviours has been hypothesised as a
      mechanism to explain empirical findings of population health improvements during
      some economic downturns. METHODS: We estimated the effect of the local
      unemployment rate on health behaviours using pooled annual surveys from the 2003
      2010 Behavioral Risk Factor Surveillance Surveys, as well as population-based
      telephone surveys of the US adult general population. Analyses were based on
      approximately 1 million respondents aged 25 years or older living in 90
      Metropolitan Statistical Areas and Metropolitan Divisions (MMSAs). The primary
      exposure was the quarterly MMSA-specific unemployment rate. Outcomes included
      alcohol consumption, smoking status, attempts to quit smoking, body mass index,
      overweight/obesity and past-month physical activity or exercise. RESULTS: The
      average unemployment rate across MMSAs increased from a low of 4.5% in 2007 to a
      high of 9.3% in 2010. In multivariable models accounting for individual-level
      sociodemographic characteristics and MMSA and quarter fixed effects, a one
      percentage-point increase in the unemployment rate was associated with 0.15 (95%
      CI -0.31 to 0.01) fewer drinks consumed in the past month and a 0.14 (95% CI 
      0.28 to 0.00) percentage-point decrease in the prevalence of past-month heavy
      drinking; these effects were driven primarily by men. Changes in the unemployment
      rate were not consistently associated with other health behaviours. Although
      individual-level unemployment status was associated with higher levels of alcohol
      consumption, smoking and obesity, the MMSA-level effects of the recession were
      largely invariant across employment groups. CONCLUSIONS: Our results do not
      support the hypothesis that health behaviours mediate the effects of local-area
      economic conditions on mortality.

PMID- 23969347
TI  - The Greek financial crisis and homicide rates: another reason to worry.

PMID- 23969348
TI  - Systematic differences among never, occasional and moderate alcohol users in
      southern China, and its use in alcohol research: a cross-sectional study.
AB  - BACKGROUND: Western observational studies show moderate alcohol use, compared
      with never use, positively associated with health. Moderate users differ
      systematically from others, making these observations vulnerable to confounding.
      Observations from other contexts may help distinguish whether these associations
      are confounded. To assess whether southern Chinese would provide a more suitable
      setting to examine the association of moderate alcohol use with health, we
      compared never alcohol users with moderate alcohol users and occasional users in
      this setting. METHODS: We used age-adjusted multinomial regression to assess sex
      stratified associations of alcohol use (never, occasional (<1 occasion/week),
      moderate (<=140 g ethanol/week for women and <=210 g for men)) with health
      attributes and indicators in the Guangzhou Biobank Cohort Study (2003-2008) (n=26
      361). RESULTS: Among men, moderate alcohol users, when compared with never users,
      had slightly lower socioeconomic position and unhealthier lifestyle. Conversely,
      occasional alcohol users, when compared with never users, had higher
      socioeconomic position and healthier lifestyle. Among women, when compared with
      never users, both occasional and moderate users had higher socioeconomic position
      and healthier lifestyle. However, all alcohol users for both sexes, when compared
      with never users, were more likely to be ever smokers and to be exposed to
      secondhand smoke. CONCLUSIONS: Observations in alcohol epidemiology may be
      affected by confounding due to contextually specific systematic differences.
      Results from a particular setting should not be interpreted as causal unless they
      are verified in different populations and, preferably, in non-observational
      studies.

PMID- 23969349
TI  - Managing conflicts of interest in clinical care: the "race to the middle" at U.S.
      medical schools.
AB  - PURPOSE: National recommendations specify how medical schools should manage
      clinical conflicts of interest (CCOIs), including gifts and payments to
      physicians from pharmaceutical companies. A 2008 study showed that few schools
      had policies in keeping with the recommendations. The authors conducted a follow
      up study in 2011 to assess possible improvements. METHOD: To obtain policies in
      12 areas of CCOI, the authors searched the Web sites of all 133 medical schools
      existing in July 2011 and contacted schools that had no online policies. Policies
      were scored as no policy, permissive, moderate, or stringent, based on published
      recommendations; each school's scores were averaged to assess overall policy
      strength. Changes since 2008 were evaluated. The authors also collected
      information on schools' public/private status, hospital ownership/affiliation,
      and National Institutes of Health (NIH) funding to determine whether these
      characteristics were associated with differences in policy strength. RESULTS:
      Policies were obtained for a representative sample of 127 (95%) medical schools.
      The frequency of stringent policies increased from 2008 to 2011 in all CCOI
      areas, and medical schools' overall policy strength more than doubled. However,
      less than stringent policies remained the norm for all areas except ghostwriting.
      Greater NIH funding was associated with stronger policies in five areas and with
      higher overall policy strength. CONCLUSIONS: Schools have made great progress
      toward national standards, yet room for improvement remains: The data reveal not
      a race to the top but a shift from the bottom to the middle. Follow-up research
      should explore whether stronger policies emerge in the future.

PMID- 23969350
TI  - Clinical Spanish use and language proficiency testing among pediatric residents.
AB  - PURPOSE: To describe patterns of clinical Spanish use by pediatric residents, and
      to compare self-assessment of language proficiency against an objective language
      test. METHOD: In 2010, the authors e-mailed a survey to all 247 pediatric
      residents at three institutions, inviting those with any level of Spanish
      language ability to participate. Participants completed a survey reporting
      Spanish proficiency, interpreter use, and comfort using Spanish in a range of
      clinical scenarios. Clinical scenarios were grouped and analyzed by degree of
      complexity. Self-reported Spanish proficiency was compared with tested
      proficiency, as measured by a 20-minute telephone assessment of general language
      ability. Scores were categorized as "not proficient," "proficient," and "highly
      proficient." RESULTS: Of the 247 residents, 78 (32%) participated, self-reporting
      a range of Spanish skills; 23% of those reported spoken proficiency ("proficient"
      or "fluent"). Participants at all levels of proficiency reported using Spanish
      without interpretation, including 63% of those who were not proficient. The
      majority (56%) of nonproficient residents reported comfort using Spanish in
      straightforward clinical scenarios, and 10% reported comfort in clinical
      scenarios with legal implications. Self-reported proficiency had a positive
      predictive value of 67% for testing at a proficient level and 22% for testing at
      a highly proficient level. CONCLUSIONS: Regardless of level of Spanish
      proficiency, pediatric residents provide clinical care to patients in Spanish.
      Self-reported Spanish proficiency does not reliably predict tested ability,
      especially when using stringent criteria to define proficiency. Provider language
      "credentialing" is an important step in implementing a policy to improve care for
      limited English proficiency patients.

PMID- 23969351
TI  - To stay or not to stay? A grounded theory study of residents' postcall behaviors
      and their rationalizations for those behaviors.
AB  - PURPOSE: Although policies to restrict residents' duty hours are pervasive,
      resident adherence to restricted duty hours has proved challenging. The authors
      sought to describe residents' postcall behaviors and understand the dominant
      rationalizations underpinning their decisions to stay or not to stay after a 24
      hour shift. METHOD: Using constructivist grounded theory methodology, the authors
      conducted semistructured interviews with 24 residents across six surgical and
      nonsurgical specialty programs at one Canadian institution during 2012. They
      analyzed transcripts iteratively using a constant comparative method of
      identifying and refining key themes as the data set accrued, and theoretically
      sampling until theme saturation. RESULTS: Abiding by cultural norms was the
      dominant rationalization for both choosing to continue to work postcall or to go
      home. Cutting across this dominant theme were three subcategories
      (infrastructure, invoking values, and negotiating tension) with a pattern of
      residents invoking similar values of patient safety and education regardless of
      the cultural norms of their program, the infrastructure within which they worked,
      or the tensions they were navigating. CONCLUSIONS: Although central to residents'
      rationalizations, values appear to be versatile, amenable to multiple, even
      conflicting, applications. Residents perceived that they were upholding the
      values of patient safety and education regardless of which postcall behavior they
      chose-staying or going. Based on this, for duty hours reform initiatives to be
      successful, a shift to emphasizing organizational changes will be required to
      reduce the circumstances in which postcall behavior is an individual, values
      based decision.

PMID- 23969352
TI  - Understanding clinical uncertainty: what is going on when experienced surgeons
      are not sure what to do?
AB  - PURPOSE: In clinical settings, uncertainty is part of everyday practice. However,
      a lack of insight into how experts approach uncertainty limits the ability to
      explicitly teach and assess it in training. This study explored how experienced
      surgeons perceived and handled uncertainty during challenging intraoperative
      situations, to develop a theoretical language supporting both education and
      research. METHOD: This constructivist qualitative study included observations and
      interviews during 26 surgical cases. The cases, drawn from seven staff surgeons
      from various specialties at a medical school, were purposively sampled after
      being preidentified by the surgeon as "likely challenging." The authors combined
      template and inductive analyses. In template analysis, an existing theory was
      used to identify instances of uncertainty in the dataset. Inductive analysis was
      used to elaborate and refine the concepts. RESULTS: Template analysis confirmed
      that existing theoretical concepts are relevant to surgery. However, inductive
      analysis revealed additional concepts and positioned existing concepts within new
      relationships. Two new theoretical themes were recognizing uncertainty and
      responding to uncertainty, each with corresponding subthemes. Factors such as the
      novelty of the situation, difficulty in predicting the outcome, and difficulty
      deciding the course of action mainly characterize an uncertain situation in
      surgery according to the participants. CONCLUSIONS: The results offer a refined
      language for conceptualizing uncertainty in surgery. Although further research
      could elaborate and test the explanatory power of this language, the authors
      anticipate that it has implications both for current discussions of surgical
      safety and for future development of explicit training for effective management
      of surgical uncertainty.

PMID- 23969353
TI  - Primary care, the ROAD less traveled: what first-year medical students want in a
      specialty.
AB  - PURPOSE: Medical students are increasingly choosing non-primary-care specialties.
      Students consider lifestyle in selecting their specialty, but how entering
      medical students perceive lifestyle is unknown. This study investigates how first
      year students value or rate lifestyle domains and specialty-selection
      characteristics and whether their ratings vary by interest in primary care (PC).
      METHOD: During the 2012-2013 academic year, the authors conducted a cross
      sectional survey of first-year medical students from 11 MD-granting medical
      schools. Using a five-point Likert-type scale (1 = not important at all; 5 =
      extremely important), respondents rated the importance of 5 domains of good
      lifestyle and 21 characteristics related to specialty selection. The authors
      classified students into five groups by PC interest and assessed differences by
      PC interest using one-way analysis of variance. RESULTS: Of 1,704 participants,
      1,020 responded (60%). The option "type of work I am doing" was the highest-rated
      lifestyle domain (mean 4.8, standard deviation [SD] 0.6). "Being satisfied with
      the job" was the highest-rated specialty-selection characteristic (mean 4.7, SD
      0.5). "Availability of practice locations in rural areas" was rated lowest (mean
      2.0, SD 1.1). As PC interest decreased, the importance of "opportunities to work
      with underserved populations" also decreased, but importance of "average salary
      earned" increased (effect sizes of 0.98 and 0.94, respectively). CONCLUSIONS:
      First-year students valued enjoying work. The importance of financial
      compensation was inversely associated with interest in PC. Examining the
      determinants of enjoyable work may inform interventions to help students attain
      professional fulfillment in PC.

PMID- 23969354
TI  - Are we all on the same page? A discourse analysis of interprofessional
      collaboration.
AB  - PURPOSE: Interprofessional collaboration (IPC) has become a dominant idea in both
      medical education and clinical care as reflected in its incorporation into
      competency-based educational frameworks and hospital accreditation models. This
      study examined the published literature to explore whether a shared IPC discourse
      underpins these current efforts. METHOD: Using a critical discourse analysis
      methodology informed by Michel Foucault's approach, the authors analyzed an
      archive of 188 texts published from 1960 through 2011. The authors identified the
      texts through a search of PubMed and CINAHL. RESULTS: The authors identified two
      major discourses in IPC: utilitarian and emancipatory. The utilitarian discourse
      is characterized by a positivist, experimental approach to the question of
      whether IPC is useful in patient care and, if so, what features best promote
      successful outcomes. This discourse uses the language of "evidence" and
      "validity." The emancipatory discourse is characterized by a constructivist
      approach concerned primarily with equalizing power relations among health
      practitioners; its language includes "power" and "dominance." CONCLUSIONS: This
      study suggests that IPC is not a single, coherent idea in medical education and
      health care. At least two different IPC discourses exist, each with its own
      distinctive truths, objects, and language. The extent to which educators and
      health care practitioners may tacitly align with one discourse or the other may
      explain the tensions that have accompanied the conceptualization, implementation,
      and assessment of IPC. Explicit acknowledgment of and attention to these
      discourses could improve the coherence and impact of IPC efforts in educational
      and clinical settings.

PMID- 23969355
TI  - Comparing diagnostic performance and the utility of clinical vignette-based
      assessment under testing conditions designed to encourage either automatic or
      analytic thought.
AB  - PURPOSE: Although decades of research have yielded considerable insight into
      physicians' clinical reasoning processes, assessing these processes remains
      challenging; thus, the authors sought to compare diagnostic performance and the
      utility of clinical vignette-based assessment under testing conditions designed
      to encourage either automatic or analytic thought. METHOD: This 2011-2012
      multicenter randomized study of 393 clinicians (medical students, postgraduate
      trainees, and faculty) measured diagnostic accuracy on clinical vignettes under
      two conditions: one encouraged participants to give their first impression (FI),
      and the other led participants through a directed search (DS) for the correct
      diagnosis. The authors compared accuracy, feasibility, reliability, and relation
      to United States Medical Licensing Exam (USMLE) scores under each condition.
      RESULTS: A 2 (instructional condition) * 2 (vignette complexity) * 3 (experience
      level) analysis of variance revealed no difference in accuracy as a function of
      instructional condition (F[1,379] = 2.44, P = .12), but demonstrated the expected
      main effects of vignette complexity (F[1,379] = 965.2, P < .001) and experience
      (F[2,379] = 39.6, P < .001). Pearson correlations revealed greater associations
      between assessment scores and USMLE performance in the FI condition than in the
      DS condition (P < .001). Spearman-Brown calculations consistently indicated that
      alpha >= 0.75 could be achieved more efficiently under the FI condition relative
      to the DS condition. CONCLUSIONS: Instructions to trust one's first impres-sions
      result in similar performance when compared with instructions to consider
      clinical information in a systematic fashion, but have greater utility when used
      for the purposes of assessment.

PMID- 23969356
TI  - The design of a medical school social justice curriculum.
AB  - The acquisition of skills to recognize and redress adverse social determinants of
      disease is an important component of undergraduate medical education. In this
      article, the authors justify and define "social justice curriculum" and then
      describe the medical school social justice curriculum designed by the
      multidisciplinary Social Justice Vertical Integration Group (SJVIG) at the Geisel
      School of Medicine at Dartmouth. The SJVIG addressed five goals: (1) to define
      core competencies in social justice education, (2) to identify key topics that a
      social justice curriculum should cover, (3) to assess social justice curricula at
      other institutions, (4) to catalog institutionally affiliated community outreach
      sites at which teaching could be paired with hands-on service work, and (5) to
      provide examples of the integration of social justice teaching into the core
      (i.e., basic science) curriculum. The SJVIG felt a social justice curriculum
      should cover the scope of health disparities, reasons to address health
      disparities, and means of addressing these disparities. The group recommended
      competency-based student evaluations and advocated assessing the impact of
      medical students' social justice work on communities. The group identified the
      use of class discussion of physicians' obligation to participate in social
      justice work as an educational tool, and they emphasized the importance of a
      mandatory, longitudinal, immersive, mentored community outreach practicum.
      Faculty and administrators are implementing these changes as part of an overall
      curriculum redesign (2012-2015). A well-designed medical school social justice
      curriculum should improve student recognition and rectification of adverse social
      determinants of disease. 

PMID- 23969357
TI  - Fostering innovation in medicine and health care: what must academic health
      centers do?
AB  - There is a real need for innovation in health care delivery, as well as in
      medicine, to address related challenges of access, quality, and affordability
      through new and creative approaches. Health care environments must foster
      innovation, not just allowing it but actively encouraging it to happen anywhere
      and at every level in health care and medicine-from the laboratory, to the
      operating room, bedside, and clinics. This paper reviews the essential elements
      and environmental factors important for health-related innovation to flourish in
      academic health systems.The authors maintain that innovation must be actively
      cultivated by teaching it, creating "space" for and supporting it, and providing
      opportunities for its implementation. The authors seek to show the importance of
      these three fundamental principles and how they can be implemented, highlighting
      examples from across the country and their own institution.Health innovation
      cannot be relegated to a second-class status by the urgency of day-to-day
      operations, patient care, and the requirements of traditional research.
      Innovation needs to be elevated to a committed endeavor and become a part of an
      organization's culture, particularly in academic health centers. 

PMID- 23969358
TI  - Caring for patients with limited English proficiency: are residents prepared to
      use medical interpreters?
AB  - PURPOSE: To evaluate whether educational sessions on interpreter use and
      experience with interpreters are associated with resident self-efficacy in the
      use of professional interpreters. METHOD: In 2010, the authors surveyed residents
      from seven pediatric residency programs. Their 29-item survey collected data on
      training and experience with interpreters and self-efficacy in (1) determining
      when an interpreter is needed and (2) using a professional interpreter. The
      authors conducted bivariate and multivariate regression analyses. RESULTS: Among
      the 271 respondents, 82% reported that >= 10% of their patients had limited
      English proficiency (LEP), 53% indicated they had "a lot" of experience with
      interpreters, and 54% reported never receiving any educational sessions on
      interpreter use. The majority reported high self-efficacy in knowing when an
      interpreter is needed (69%) and in using an interpreter (68%). Residents
      reporting a high experience level with interpreters were more likely to report
      high self-efficacy in knowing when an interpreter is needed (odds ratio [OR] =
      1.85; 95% confidence interval[CI] = 1.03-3.32) and in using an interpreter (OR =
      3.97; 95% CI = 1.19-13.31). Formal training on using interpreters was also
      associated with high self-efficacy in interpreter use(OR = 1.62; 95% CI = 1.22
      2.14). CONCLUSIONS: Many residents who care for patients with LEP have never
      received educational sessions on interpreter use. Such training is associated
      with high self-efficacy and may enhance patient-provider communication.
      Incorporating this training into residency programs is necessary to equip
      providers with skills to communicate with patients and families with LEP.

PMID- 23969359
TI  - Changing the culture of academic medicine to eliminate the gender leadership gap:
      50/50 by 2020.
AB  - Central to the daily struggles that successful working women face is the
      misalignment of the current work culture and the values of the workforce. In
      addition to contributing to work-life integration conflicts, this disconnect
      perpetuates the gender leadership gap. The dearth of women at the highest ranks
      of academic medicine not only sends a clear message to women that they must
      choose between career advancement and their personal life but also represents a
      loss of talent for academic health centers as they fail to recruit and retain the
      best and the brightest. To close the gender leadership gap and to meet the needs
      of the next generation of physicians, scientists, and educators, the authors
      argue that the culture of academic medicine must change to one in which
      flexibility and work-life integration are core parts of the definition of
      success. Faculty must see flexibility policies, such as tenure clock extensions
      and parental leaves, as career advancing rather than career limiting. To achieve
      these goals, the authors describe the Stanford University School of Medicine
      Academic Biomedical Career Customization (ABCC) model. This framework includes
      individualized career plans, which span a faculty member's career, with options
      to flex up or down in research, patient care, administration, and teaching, and
      mentoring discussions, which ensure that faculty take full advantage of the
      existing policies designed to make career customization possible. The authors
      argue that with vision, determination, and focus, the academic medicine community
      can eliminate the gender leadership gap to achieve 50/50 by 2020. 

PMID- 23969360
TI  - Aligning academic continuing medical education with quality improvement: a model
      for the 21st century.
AB  - The recent health care quality improvement (QI) movement has called for
      significant changes to the way that health care is delivered and taught in
      academic medical centers (AMCs). This movement also has affected academic
      continuing medical education (CME). In January 2011, to better align the CME and
      QI efforts of AMCs, the Association of American Medical Colleges (AAMC) launched
      a pilot initiative called Aligning and Educating for Quality (ae4Q). The goal of
      this pilot was to assist 11 AMCs as they moved to a more integrated model of
      continuous performance improvement by aligning their quality measurement and
      improvement with their continuing education endeavors. In this article, the
      authors describe the development of the ae4Q pilot and the resulting outcomes
      that have led to ongoing improvements.During the 18-month pilot, AAMC consultants
      conducted readiness assessments and on-site visits and provided consultation
      services and Web-based resources based on the AMC's needs. Following these
      interventions at each site, they then conducted both interviews with participants
      and postintervention assessment surveys to measure the impact of the pilot.
      Findings included demonstrated increases in the alignment of CME and QI, a
      greater use of quality data in CME design and delivery, and a greater use of CME
      as an intervention for clinical improvement. Two sites also attributed
      measureable improved clinical outcomes to their participation in the ae4Q pilot.
      The AAMC has used these findings to create resources and ongoing services to
      support AMCs as they pursue efforts to align QI and CME. 

PMID- 23969361
TI  - "I am a doctor": negotiating the discourses of standardization and diversity in
      professional identity construction.
AB  - PURPOSE: Medical educators have expressed concern that students' professional
      identities do not always align with their expectations or with professional
      standards. The authors propose that, in constructing appropriate professional
      identities, medical students today are affected by the competing discourses of
      diversity and standardization. METHOD: Between March and May 2012, the authors
      conducted a critical review of seminal publications to highlight the discourses
      of diversity and standardization in the medical education literature. They
      surveyed the social sciences literature on identity construction and drew
      examples from medical education to demonstrate how a social constructionist
      approach could inform the discussion about how medical students' professional
      identities are affected by these discourses. RESULTS: The discourse of diversity
      emphasizes individuality, difference, and a plurality of possibilities and
      advances the notion that heterogeneity is beneficial to medical education and to
      patients. In contrast, the discourse of standardization strives for homogeneity,
      sameness, and a limited range of possibilities and conveys that there is a single
      way to be a competent, professional physician. Thus, these discourses are in
      tension, a fact that medical educators largely have ignored. A social
      constructionist approach to identity suggests that medical students resolve this
      tension in different ways and construct different identities as a result.
      CONCLUSIONS: To influence medical students' professional identity construction,
      the authors advocate that educators seek change across the profession-faculty
      must acknowledge and take advantage of the tension between the discourses of
      standardization and diversity.

PMID- 23969362
TI  - Validity evidence for a patient note scoring rubric based on the new patient note
      format of the United States Medical Licensing Examination.
AB  - PURPOSE: This study examines validity evidence for the Patient Note Scoring
      Rubric, which was developed for a local graduation competency exam (GCE) to
      assess patient notes written in the new United States Medical Licensing
      Examination (USMLE) Step 2 Clinical Skills format. The rubric was designed to
      measure three dimensions: Documentation, justified differential diagnosis (DDX),
      and Workup. METHOD: Analyses used GCE data from 170 fourth-year medical students
      who completed five standardized patient (SP) cases in May 2012. Five physician
      raters each scored all responses for one case. Internal structure was examined
      using correlations between dimensions and between cases; a generalizability study
      was also conducted. Relationship to other variables was examined by correlating
      patient note scores with SP encounter scores. Consequence was assessed by
      comparing pass-fail rates between the rubric and the previous global rating.
      Response process was examined using rater feedback. RESULTS: Correlations between
      scores from different dimensions ranged between 0.33 and 0.44. Reliability of
      scores based on the phi coefficient was 0.43; 15 cases were required to reach a
      phi coefficient of 0.70. Evidence of case specificity was found. Documentation
      scores were moderately correlated with SP scores for data gathering (r = 0.47, P
      < .001). There was no meaningful change in pass-fail rates. Raters' feedback
      indicated that they required more training for scoring the DDX and Workup
      dimensions. CONCLUSIONS: There is initial validity evidence for use of this
      rubric to score local clinical exams that are based on the new USMLE patient note
      format.

PMID- 23969363
TI  - The development of scientific communication skills: a qualitative study of the
      perceptions of trainees and their mentors.
AB  - PURPOSE: Scientific communication, both written and oral, is the cornerstone of
      success in biomedical research, yet formal instruction is rarely provided.
      Trainees with little exposure to standard academic English may find developing
      scientific communication skills challenging. In this exploratory, hypothesis
      generating qualitative study, the authors examined the process by which mentored
      junior researchers learn scientific communication skills, their feelings about
      the challenges, and their mentor's role in the process. METHOD: In 2010, the
      authors conducted semistructured focus groups and interviews to explore research
      trainees' and faculty mentors' perceptions and practices regarding scientific
      communication skills development, as part of the development phase of a larger
      quantitative study. The facilitator took detailed notes and verified their
      accuracy with participants during the sessions; a second member of the research
      team observed and verified the recorded notes. Three coders performed a thematic
      analysis, and the other authors reviewed it. RESULTS: Forty-three trainees and 50
      mentors participated. Trainees and mentors had diverging views on the role of
      mentoring in fostering communication skills development. Trainees expressed
      varying levels of self-confidence but considerable angst. Mentors felt that most
      trainees have low self-confidence. Trainees expressed interest in learning
      scientific communication skills, but mentors reported that some trainees were
      insufficiently motivated and seemed resistant to guidance. Both groups agreed
      that trainees found mentors' feedback difficult to accept. CONCLUSIONS: The
      degree of distress, dissatisfaction, and lack of mutual understanding between
      mentors and trainees was striking. These themes have important implications for
      best practices and resource development.

PMID- 23969364
TI  - Assessing residents' written learning goals and goal writing skill: validity
      evidence for the learning goal scoring rubric.
AB  - PURPOSE: To provide validity evidence for use of the Learning Goal Scoring Rubric
      to assess the quality of written learning goals and residents' goal writing
      skills. METHOD: This two-part study used the rubric to assess University of
      Colorado third-year pediatric residents' written learning goals to obtain
      validity evidence. In study 1, five raters independently scored 48 goals written
      in 2010-2011 and 2011-2012 by 48 residents, who also responded to the Jefferson
      Scale of Physician Lifelong Learning (JeffSPLL). In study 2, two raters
      independently scored 48 goals written in 2011-2012 by 12 residents. Intraclass
      correlation coefficients (ICCs) assessed rater agreement to provide evidence for
      response process. Generalizability theory assessed internal structure.
      Independent-samples Mann-Whitney U tests and correlations assessed relationship
      to other variables. Content was matched to published literature and instructional
      methods. RESULTS: The ICC was 0.71 for the overall rubric. In study 1, where the
      generalizability study's (G study's) object of measurement was learning goals,
      the phi coefficient was 0.867. In study 2, where the G study's object of
      measurement was the resident (goal writing skill), the phi coefficient was 0.751.
      The total mean score of residents with goal writing training was significantly
      higher than that of those without (7.54 versus 4.98, P < .001). Correlation
      between goal quality and JeffSPLL score was not significant. Investigators agreed
      that the content matched the published literature and instructional methods.
      CONCLUSIONS: Preliminary validity evidence indicates that this scoring rubric can
      assess learning goal quality and goal writing skill.

PMID- 23969365
TI  - Sponsorship: a path to the academic medicine C-suite for women faculty?
AB  - Despite increases in the percentages of women medical school graduates and
      faculty over the past decade, women physicians and scientists remain
      underrepresented in academic medicine's highest-level executive positions, known
      as the "C-suite." The challenges of today and the future require novel approaches
      and solutions that depend on having diverse leaders. Such diversity has been
      widely shown to be critical to creating initiatives and solving complex problems
      such as those facing academic medicine and science. However, neither formal
      mentoring programs focused on individual career development nor executive
      coaching programs focused on individual job performance have led to substantial
      increases in the proportion of women in academic medicine's top leadership
      positions.Faced with a similar dilemma, the corporate world has initiated
      sponsorship programs designed to accelerate the careers of women as leaders.
      Sponsors differ from mentors and coaches in one key area: They have the position
      and power to advocate publicly for the advancement of nascent talent, including
      women, in the organization. Although academic medicine differs from the corporate
      world, the strong sponsorship programs that have advanced women into
      corporations' upper levels of leadership can serve as models for sponsorship
      programs to launch new leaders in academic medicine. 

PMID- 23969366
TI  - Practice indicators of suboptimal care and avoidable adverse events: a content
      analysis of a national qualifying examination.
AB  - PURPOSE: To (1) compile an initial list of physician-related practice indicators
      (PRINDs) that contribute to causing or preventing suboptimal care (SOCR) and
      adverse events (AEs) and (2) determine the extent to which one national exam
      assessed these PRINDs. METHOD: In 2009-2010, the authors searched the literature
      and surveyed 17 physician experts to compile a list of PRINDs of SOCR and
      avoidable AEs. They then conducted a content analysis of the 2008 and 2009
      Medical Council of Canada (MCC) Qualifying Examinations (QEs). RESULTS: The
      authors identified 92 unique PRINDs, of which 59 were behaviors or decisions
      expected of all physicians and suitable for assessment on a general medical
      examination. Of these, 36 (61%) were tested on the 2008 and 2009 MCC QEs. The
      mean number of PRINDs tested per exam was highest for Part I Knowledge (32.2),
      followed by Part I clinical decision making (CDM) (18.4) and Part II clinical
      performance (objective structured clinical examination [OSCE]) (9.8). The
      percentage of questions or cases per exam testing a PRIND (e.g., 14/36 [39%] for
      CDM and 5.26/12 [44%] for OSCE) differed from the percentage of the total test
      score attributed to PRINDs (e.g., 10.8/36 [30%] for CDM and 68.5/1,522.3 [5%] for
      OSCE). CONCLUSIONS: PRINDs represent candidates' abilities to avoid SOCR and AEs
      and constitute an important aspect of medical practice to be assessed on
      licensing or certifying examinations to best protect the public. The different
      scoring methods used to measure such knowledge and skills warrant further
      consideration.

PMID- 23969367
TI  - Medical education reimagined: a call to action.
AB  - The authors propose a new model for medical education based on the "flipped
      classroom" design. In this model, students would access brief (~10 minute) online
      videos to learn new concepts on their own time. The content could be viewed by
      the students as many times as necessary to master the knowledge in preparation
      for classroom time facilitated by expert faculty leading dynamic, interactive
      sessions where students can apply their newly mastered knowledge.The authors
      argue that the modern digitally empowered learner, the unremitting expansion of
      biomedical knowledge, and the increasing specialization within the practice of
      medicine drive the need to reimagine medical education. The changes that they
      propose emphasize the need to define a core curriculum that can meet learners
      where they are in a digitally oriented world, enhance the relevance and retention
      of knowledge through rich interactive exercises, and facilitate in-depth learning
      fueled by individual students' aptitude and passion. The creation and adoption of
      this model would be meaningfully enhanced by cooperative efforts across medical
      schools. 

PMID- 23969368
TI  - Just imagine: new paradigms for medical education.
AB  - For all its traditional successes, the current model of medical education in the
      United States and Canada is being challenged on issues of quality, throughput,
      and cost, a process that has exposed numerous shortcomings in its efforts to meet
      the needs of the nations' health care systems. A radical change in direction is
      required because the current path will not lead to a solution.The 2010
      publication Educating Physicians: A Call for Reform of Medical School and
      Residency identifies several goals for improving the medical education system,
      and proposals have been made to reform medical education to meet these goals.
      Enacting these recommendations practically and efficiently, while training more
      health care providers at a lower cost, is challenging.To advance solutions, the
      authors review innovations that are disrupting higher education and describe a
      vision for using these to create a new model for competency-based, learner
      centered medical education that can better meet the needs of the health care
      system while adhering to the spirit of the above proposals. These innovations
      include collaboration amongst medical schools to develop massive open online
      courses for didactic content; faculty working in small groups to leverage this
      online content in a "flipped-classroom" model; and digital badges for
      credentialing entrustable professional activities over the continuum of learning.

PMID- 23969369
TI  - Educating future physicians to track health care quality: feasibility and
      perceived impact of a health care quality report card for medical students.
AB  - PURPOSE: Quality improvement (QI) requires measurement, but medical schools
      rarely provide opportunities for students to measure their patient outcomes. The
      authors tested the feasibility and perceived impact of a quality metric report
      card as part of an Education-Centered Medical Home longitudinal curriculum.
      METHOD: Student teams were embedded into faculty practices and assigned a panel
      of patients to follow longitudinally. Students performed retrospective chart
      reviews and reported deidentified data on 30 nationally endorsed QI metrics for
      their assigned patients. Scorecards were created for each clinic team. Students
      completed pre/post surveys on self-perceived QI skills. RESULTS: A total of 405
      of their patients' charts were abstracted by 149 students (76% response rate;
      mean 2.7 charts/student). Median abstraction time was 21.8 (range: 13.1-37.1)
      minutes. Abstracted data confirmed that the students had successfully recruited a
      "high-risk" patient panel. Initial performance on abstracted quality measures
      ranged from 100% adherence on the use of beta-blockers in postmyocardial
      infarction patients to 24% on documentation of dilated diabetic eye exams. After
      the chart abstraction assignment, grand rounds, and background readings, student
      self-assessment of their perceived QI skills significantly increased for all
      metrics, though it remained low. CONCLUSIONS: Creation of an actionable health
      care quality report card as part of an ambulatory longitudinal experience is
      feasible, and it improves student perception of QI skills. Future research will
      aim to use statistical process control methods to track health care quality
      prospectively as our students use their scorecards to drive clinic-level
      improvement efforts.

PMID- 23969370
TI  - The third-year medical student "grapevine": managing transitions between third
      year clerkships using peer-to-peer handoffs.
AB  - PURPOSE: As third-year medical students rotate between clerkships, they
      experience multiple transitions across workplace cultures and shifting learning
      expectations. The authors explored clerkship transitions from the students'
      perspective by examining the advice they passed on to their peers in preparation
      for new clerkships. METHOD: Seventy-one students from three Veterans Affairs
      based clerkship rotations at the University of California, San Francisco, School
      of Medicine participated in a peer-to-peer handoff session from 2008 to 2011. In
      the handoff session, they gave tips for optimizing performance to students
      starting the clerkship they had just completed. The authors transcribed student
      comments from four handoff sessions and used qualitative content analysis to
      identify and compare advice across clerkships. RESULTS: Students shared advice
      about workplace culture, content learning, logistics, and work-life balance.
      Common themes included expectations of the rotation, workplace norms, specific
      tasks, learning opportunities, and learning strategies. Comments about patient
      care and work-life balance were rare. Students emphasized different themes for
      each clerkship; for example, for some clerkships, students commented heavily on
      tasks and content learning, while in another students focused on workplace
      culture and exam preparation. CONCLUSIONS: These findings characterize the
      transitions that third-year students undergo as they rotate into new clinical
      training environments. Students emphasized different aspects of each clerkship in
      the advice they passed to their peers, and their comments often describe informal
      norms or opportunities that official clerkship orientations may not address. Peer
      to-peer handoffs may help ease transitions between clerkships with dissimilar
      cultures and expectations.

PMID- 23969371
TI  - Do in-training evaluation reports deserve their bad reputations? A study of the
      reliability and predictive ability of ITER scores and narrative comments.
AB  - PURPOSE: Although scores on in-training evaluation reports (ITERs) are often
      criticized for poor reliability and validity, ITER comments may yield valuable
      information. The authors assessed across-rotation reliability of ITER scores in
      one internal medicine program, ability of ITER scores and comments to predict
      postgraduate year three (PGY3) performance, and reliability and incremental
      predictive validity of attendings' analysis of written comments. METHOD: Numeric
      and narrative data from the first two years of ITERs for one cohort of residents
      at the University of Toronto Faculty of Medicine (2009-2011) were assessed for
      reliability and predictive validity of third-year performance. Twenty-four
      faculty attendings rank-ordered comments (without scores) such that each resident
      was ranked by three faculty. Mean ITER scores and comment rankings were submitted
      to regression analyses; dependent variables were PGY3 ITER scores and program
      directors' rankings. RESULTS: Reliabilities of ITER scores across nine rotations
      for 63 residents were 0.53 for both postgraduate year one (PGY1) and postgraduate
      year two (PGY2). Interrater reliabilities across three attendings' rankings were
      0.83 for PGY1 and 0.79 for PGY2. There were strong correlations between ITER
      scores and comments within each year (0.72 and 0.70). Regressions revealed that
      PGY1 and PGY2 ITER scores collectively explained 25% of variance in PGY3 scores
      and 46% of variance in PGY3 rankings. Comment rankings did not improve
      predictions. CONCLUSIONS: ITER scores across multiple rotations showed decent
      reliability and predictive validity. Comment ranks did not add to the predictive
      ability, but correlation analyses suggest that trainee performance can be
      measured through these comments.

PMID- 23969372
TI  - Assessing the impact of electronic health records as an enabler of hospital
      quality and patient satisfaction.
AB  - PURPOSE: To assess the impact of using an advanced electronic health record (EHR)
      on hospital quality and patient satisfaction. METHOD: This retrospective, cross
      sectional analysis was conducted in 2012 to evaluate the association between
      advanced EHR use (Healthcare Information Management Systems Society [HIMSS] Stage
      6 or 7 as of December 2012) and estimated process and experience of care scores
      for hospitals under the Medicare Hospital Value-Based Purchasing Program, using
      data from the American Hospital Association for 2008 to 2010. Generalized linear
      regression models were fit to test the association between advanced EHR use with
      process of care and experience of care, controlling for hospital characteristics.
      In a second analysis, the models included variables to account for HIMSS stage of
      advanced EHR use. RESULTS: The study included 2,988 hospitals, with 248 (8.3%)
      classified as advanced EHR users (HIMSS Stage 6 or 7). After controlling for
      hospital characteristics, advanced EHR use was associated with a 4.2-point-higher
      process of care score (P < .001). Hospitals with Stage 7 EHRs had 11.7 points
      higher process of care scores, but Stage 6 users had scores that were not
      substantially different from those of nonadvanced users. There was no significant
      difference in estimated experience of care scores by level of advanced EHR use.
      CONCLUSIONS: This study evaluated the effectiveness of the U.S. federal
      government's investment in hospital information technology infrastructure.
      Results suggest that the most advanced EHRs have the greatest payoff in improving
      clinical process of care scores, without detrimentally impacting the patient
      experience.

PMID- 23969373
TI  - It's academic: public policy activities among faculty members in a department of
      medicine.
AB  - PROBLEM: To investigate whether and how faculty members in a department of
      medicine are engaged in public policy activities. APPROACH: Between February and
      April 2011, the authors conducted a cross-sectional, Web-based survey of all
      active Department of Medicine faculty members at the University of California,
      San Francisco. Survey questions covered demographics, academic role, academic
      rank, and participation in three specific public policy activities during the
      past five years: (1) policy-related research, (2) expert advice to government
      officials, and (3) public policy advocacy in collaboration with organizations
      outside government. OUTCOMES: Two hundred twenty of 553 faculty (40%) responded
      to the survey. One hundred twenty-four faculty members (56% of respondents and
      22% of total active faculty) reported that they were engaged in at least one of
      the three types of policy-related activities: 51 (23%) conducted policy-related
      research, 67 (30%) provided expert advice to government officials, and 93 (42%)
      collaborated with organizations to advocate for public policy. Higher faculty
      rank was significantly associated with faculty members reporting that they were
      involved in one or more of the three policy activities (P = .04). NEXT STEPS:
      Academic departments should identify public policy expertise among their faculty
      and leverage this expertise by facilitating opportunities to develop a shared
      faculty awareness of their public policy activities, by supporting the
      establishment of mentoring relationships for less experienced faculty in the area
      of public policy, and by incorporating standards of excellence for work in public
      policy into the promotions process.

PMID- 23969374
TI  - RIME foreword: a behind-the-scenes look at this year's Research in Medical
      Education Program.

PMID- 23969375
TI  - Cognition before curriculum: rethinking the integration of basic science and
      clinical learning.
AB  - PURPOSE: Integrating basic science and clinical concepts in the undergraduate
      medical curriculum is an important challenge for medical education. The health
      professions education literature includes a variety of educational strategies for
      integrating basic science and clinical concepts at multiple levels of the
      curriculum. To date, assessment of this literature has been limited. METHOD: In
      this critical narrative review, the authors analyzed literature published in the
      last 30 years (1982-2012) using a previously published integration framework.
      They included studies that documented approaches to integration at the level of
      programs, courses, or teaching sessions and that aimed to improve learning
      outcomes. The authors evaluated these studies for evidence of successful
      integration and to identify factors that contribute to integration. RESULTS:
      Several strategies at the program and course level are well described but poorly
      evaluated. Multiple factors contribute to successful learning, so identifying how
      interventions at these levels result in successful integration is difficult.
      Evidence from session-level interventions and experimental studies suggests that
      integration can be achieved if learning interventions attempt to link basic and
      clinical science in a causal relationship. These interventions attend to how
      learners connect different domains of knowledge and suggest that successful
      integration requires learners to build cognitive associations between basic and
      clinical science. CONCLUSIONS: One way of understanding the integration of basic
      and clinical science is as a cognitive activity occurring within learners. This
      perspective suggests that learner-centered, content-focused, and session-level
      oriented strategies can achieve cognitive integration.

PMID- 23969376
TI  - Reduction of venous thromboembolism (VTE) in hospitalized patients: aligning
      continuing education with interprofessional team-based quality improvement in an
      academic medical center.
AB  - PROBLEM: Despite clear prophylactic guidelines and national quality emphasis, a
      minority of hospitalized patients receive appropriate prophylaxis for venous
      thromboembolism (VTE). Data from the University of Kansas Hospital (KUH) revealed
      an unacceptably high incidence of VTE. APPROACH: The authors aligned continuing
      education with quality improvement through formation of an interprofessional,
      multidisciplinary team to develop strategic educational and system operational
      plans to decrease VTE incidence. The authors reviewed 261 charts with the
      secondary diagnosis of VTE for identification of themes or causes of VTE to
      develop multipronged educational and system-based action plans. The authors
      reviewed a "menu" of evidence-based content delivery techniques to develop the
      educational plan. Multiple noneducational adjunct system strategies were also
      developed and implemented. OUTCOMES: After implementation of all specific action
      plans, the KUH VTE incidence decreased 51% from November 2010 to June 2012 (from
      12.68 to 6.10 per 1,000 patients). Insertion of peripherally inserted central
      catheters, a common identified theme, dropped from almost 360 insertions in
      December of 2010 to less than 200 insertions in April 2012. NEXT STEPS: Aligning
      continuing education with quality improvement through an interprofessional,
      multidisciplinary team approach was associated with a decrease in VTE. The
      authors describe challenges and lessons learned to inform implementation of
      similar quality-improvement-driven continuing education initiatives elsewhere.
      Challenges included time, resources, multiple service lines, and departments with
      variable acceptance of data. Lessons learned included the value of leadership
      commitment, interprofessional team work, assessing individual data, expertise of
      continuing education, using multiple educational methods, and the need for
      overall champions.

PMID- 23969377
TI  - Video-assisted thoracic surgery for esophagus for treating locally recurrent
      gastric cancer at the anastomotic site.
AB  - OBJECTIVE: To report a case of video-assisted thoracic surgery for esophagus
      (VATS-E) for the treatment of locally recurrent gastric cancer at the anastomotic
      site. CLINICAL PRESENTATION AND INTERVENTION: A 59-year-old man underwent total
      gastrectomy for gastric cancer. Histopathologically, it was mucinous
      adenocarcinoma [pT1(sm), pN1, sM0, PM(-), DM(-), stage IB]. Local recurrence was
      detected and he received chemotherapy and radiotherapy; histopathologically, it
      was identified as mucinous adenocarcinoma [pT1(sm), pN0, sM0, stage IA]. As the
      local recurrence was uncontrollable, he underwent VATS-E. At the 1-year follow
      up, he was recurrence-free. CONCLUSION: The VATS-E minimally invasive surgery was
      a very useful technique for anastomotic recurrence after total gastrectomy in our
      patient.

PMID- 23969379
TI  - Evidence that stress per se has a role in the precipitation and natural history
      of depressive illness.

PMID- 23969380
TI  - A coarse to fine minutiae-based latent palmprint matching.
AB  - With the availability of live-scan palmprint technology, high resolution
      palmprint recognition has started to receive significant attention in forensics
      and law enforcement. In forensic applications, latent palmprints provide critical
      evidence as it is estimated that about 30 percent of the latents recovered at
      crime scenes are those of palms. Most of the available high-resolution palmprint
      matching algorithms essentially follow the minutiae-based fingerprint matching
      strategy. Considering the large number of minutiae (about 1,000 minutiae in a
      full palmprint compared to about 100 minutiae in a rolled fingerprint) and large
      area of foreground region in full palmprints, novel strategies need to be
      developed for efficient and robust latent palmprint matching. In this paper, a
      coarse to fine matching strategy based on minutiae clustering and minutiae match
      propagation is designed specifically for palmprint matching. To deal with the
      large number of minutiae, a local feature-based minutiae clustering algorithm is
      designed to cluster minutiae into several groups such that minutiae belonging to
      the same group have similar local characteristics. The coarse matching is then
      performed within each cluster to establish initial minutiae correspondences
      between two palmprints. Starting with each initial correspondence, a minutiae
      match propagation algorithm searches for mated minutiae in the full palmprint.
      The proposed palmprint matching algorithm has been evaluated on a latent-to-full
      palmprint database consisting of 446 latents and 12,489 background full prints.
      The matching results show a rank-1 identification accuracy of 79.4 percent, which
      is significantly higher than the 60.8 percent identification accuracy of a state
      of-the-art latent palmprint matching algorithm on the same latent database. The
      average computation time of our algorithm for a single latent-to-full match is
      about 141 ms for genuine match and 50 ms for impostor match, on a Windows XP
      desktop system with 2.2-GHz CPU and 1.00-GB RAM. The computation time of our
      algorithm is an order of magnitude faster than a previously published state-of
      the-art-algorithm. 

PMID- 23969381
TI  - Automatic generation of co-embeddings from relational data with adaptive shaping.
AB  - In this paper, we study the co-embedding problem of how to map different types of
      patterns into one common low-dimensional space, given only the associations
      (relation values) between samples. We conduct a generic analysis to discover the
      commonalities between existing co-embedding algorithms and indirectly related
      approaches and investigate possible factors controlling the shapes and
      distributions of the co-embeddings. The primary contribution of this work is a
      novel method for computing co-embeddings, termed the automatic co-embedding with
      adaptive shaping (ACAS) algorithm, based on an efficient transformation of the co
      embedding problem. Its advantages include flexible model adaptation to the given
      data, an economical set of model variables leading to a parametric co-embedding
      formulation, and a robust model fitting criterion for model optimization based on
      a quantization procedure. The secondary contribution of this work is the
      introduction of a set of generic schemes for the qualitative analysis and
      quantitative assessment of the output of co-embedding algorithms, using existing
      labeled benchmark datasets. Experiments with synthetic and real-world datasets
      show that the proposed algorithm is very competitive compared to existing ones.

PMID- 23969382
TI  - Calibration by correlation using metric embedding from nonmetric similarities.
AB  - This paper presents a new intrinsic calibration method that allows us to
      calibrate a generic single-view point camera just by waving it around. From the
      video sequence obtained while the camera undergoes random motion, we compute the
      pairwise time correlation of the luminance signal for a subset of the pixels. We
      show that if the camera undergoes a random uniform motion, then the pairwise
      correlation of any pixels pair is a function of the distance between the pixel
      directions on the visual sphere. This leads to formalizing calibration as a
      problem of metric embedding from nonmetric measurements: We want to find the
      disposition of pixels on the visual sphere from similarities that are an unknown
      function of the distances. This problem is a generalization of multidimensional
      scaling (MDS) that has so far resisted a comprehensive observability analysis
      (can we reconstruct a metrically accurate embedding?) and a solid generic
      solution (how do we do so?). We show that the observability depends both on the
      local geometric properties (curvature) as well as on the global topological
      properties (connectedness) of the target manifold. We show that, in contrast to
      the euclidean case, on the sphere we can recover the scale of the points
      distribution, therefore obtaining a metrically accurate solution from nonmetric
      measurements. We describe an algorithm that is robust across manifolds and can
      recover a metrically accurate solution when the metric information is observable.
      We demonstrate the performance of the algorithm for several cameras (pin-hole,
      fish-eye, omnidirectional), and we obtain results comparable to calibration using
      classical methods. Additional synthetic benchmarks show that the algorithm
      performs as theoretically predicted for all corner cases of the observability
      analysis. 

PMID- 23969383
TI  - Efficient subframe video alignment using short descriptors.
AB  - This paper addresses the problem of video alignment. We present efficient
      approaches that allow for spatiotemporal alignment of two sequences. Unlike most
      related works, we consider independently moving cameras that capture a 3D scene
      at different times. The novelty of the proposed method lies in the adaptation and
      extension of an efficient information retrieval framework that casts the
      sequences as an image database and a set of query frames, respectively. The
      efficient retrieval builds on the recently proposed quad descriptor. In this
      context, we define the 3D Vote Space (VS) by aggregating votes through a
      multiquerying (multiscale) scheme and we present two solutions based on VS
      entries; a causal solution that permits online synchronization and a global
      solution through multiscale dynamic programming. In addition, we extend the
      recently introduced ECC image-alignment algorithm to the temporal dimension that
      allows for spatial registration and synchronization refinement with subframe
      accuracy. We investigate full search and quantization methods for short
      descriptors and we compare the proposed schemes with the state of the art.
      Experiments with real videos by moving or static cameras demonstrate the
      efficiency of the proposed method and verify its effectiveness with respect to
      spatiotemporal alignment accuracy. 

PMID- 23969384
TI  - Exhaustive linearization for robust camera pose and focal length estimation.
AB  - We propose a novel approach for the estimation of the pose and focal length of a
      camera from a set of 3D-to-2D point correspondences. Our method compares
      favorably to competing approaches in that it is both more accurate than existing
      closed form solutions, as well as faster and also more accurate than iterative
      ones. Our approach is inspired on the EPnP algorithm, a recent O(n) solution for
      the calibrated case. Yet we show that considering the focal length as an
      additional unknown renders the linearization and relinearization techniques of
      the original approach no longer valid, especially with large amounts of noise. We
      present new methodologies to circumvent this limitation termed exhaustive
      linearization and exhaustive relinearization which perform a systematic
      exploration of the solution space in closed form. The method is evaluated on both
      real and synthetic data, and our results show that besides producing precise
      focal length estimation, the retrieved camera pose is almost as accurate as the
      one computed using the EPnP, which assumes a calibrated camera. 

PMID- 23969385
TI  - Facial age estimation by learning from label distributions.
AB  - One of the main difficulties in facial age estimation is that the learning
      algorithms cannot expect sufficient and complete training data. Fortunately, the
      faces at close ages look quite similar since aging is a slow and smooth process.
      Inspired by this observation, instead of considering each face image as an
      instance with one label (age), this paper regards each face image as an instance
      associated with a label distribution. The label distribution covers a certain
      number of class labels, representing the degree that each label describes the
      instance. Through this way, one face image can contribute to not only the
      learning of its chronological age, but also the learning of its adjacent ages.
      Two algorithms, named IIS-LLD and CPNN, are proposed to learn from such label
      distributions. Experimental results on two aging face databases show remarkable
      advantages of the proposed label distribution learning algorithms over the
      compared single-label learning algorithms, either specially designed for age
      estimation or for general purpose. 

PMID- 23969387
TI  - Highly nonrigid object tracking via patch-based dynamic appearance modeling.
AB  - A novel tracking algorithm is proposed for targets with drastically changing
      geometric appearances over time. To track such objects, we develop a local patch
      based appearance model and provide an efficient online updating scheme that
      adaptively changes the topology between patches. In the online update process,
      the robustness of each patch is determined by analyzing the likelihood landscape
      of the patch. Based on this robustness measure, the proposed method selects the
      best feature for each patch and modifies the patch by moving, deleting, or newly
      adding it over time. Moreover, a rough object segmentation result is integrated
      into the proposed appearance model to further enhance it. The proposed framework
      easily obtains segmentation results because the local patches in the model serve
      as good seeds for the semi-supervised segmentation task. To solve the complexity
      problem attributable to the large number of patches, the Basin Hopping (BH)
      sampling method is introduced into the tracking framework. The BH sampling method
      significantly reduces computational complexity with the help of a deterministic
      local optimizer. Thus, the proposed appearance model could utilize a sufficient
      number of patches. The experimental results show that the present approach could
      track objects with drastically changing geometric appearance accurately and
      robustly. 

PMID- 23969386
TI  - Handwritten Chinese/Japanese text recognition using semi-Markov conditional
      random fields.
AB  - This paper proposes a method for handwritten Chinese/Japanese text (character
      string) recognition based on semi-Markov conditional random fields (semi-CRFs).
      The high-order semi-CRF model is defined on a lattice containing all possible
      segmentation-recognition hypotheses of a string to elegantly fuse the scores of
      candidate character recognition and the compatibilities of geometric and
      linguistic contexts by representing them in the feature functions. Based on given
      models of character recognition and compatibilities, the fusion parameters are
      optimized by minimizing the negative log-likelihood loss with a margin term on a
      training string sample set. A forward-backward lattice pruning algorithm is
      proposed to reduce the computation in training when trigram language models are
      used, and beam search techniques are investigated to accelerate the decoding
      speed. We evaluate the performance of the proposed method on unconstrained online
      handwritten text lines of three databases. On the test sets of databases CASIA
      OLHWDB (Chinese) and TUAT Kondate (Japanese), the character level correct rates
      are 95.20 and 95.44 percent, and the accurate rates are 94.54 and 94.55 percent,
      respectively. On the test set (online handwritten texts) of ICDAR 2011 Chinese
      handwriting recognition competition, the proposed method outperforms the best
      system in competition. 

PMID- 23969388
TI  - Improved object categorization and detection using comparative object similarity.
AB  - Due to the intrinsic long-tailed distribution of objects in the real world, we
      are unlikely to be able to train an object recognizer/detector with many visual
      examples for each category. We have to share visual knowledge between object
      categories to enable learning with few or no training examples. In this paper, we
      show that local object similarity information--statements that pairs of
      categories are similar or dissimilar--is a very useful cue to tie different
      categories to each other for effective knowledge transfer. The key insight: Given
      a set of object categories which are similar and a set of categories which are
      dissimilar, a good object model should respond more strongly to examples from
      similar categories than to examples from dissimilar categories. To exploit this
      category-dependent similarity regularization, we develop a regularized kernel
      machine algorithm to train kernel classifiers for categories with few or no
      training examples. We also adapt the state-of-the-art object detector to encode
      object similarity constraints. Our experiments on hundreds of categories from the
      Labelme dataset show that our regularized kernel classifiers can make significant
      improvement on object categorization. We also evaluate the improved object
      detector on the PASCAL VOC 2007 benchmark dataset. 

PMID- 23969389
TI  - Learning graphical model parameters with approximate marginal inference.
AB  - Likelihood-based learning of graphical models faces challenges of computational
      complexity and robustness to model misspecification. This paper studies methods
      that fit parameters directly to maximize a measure of the accuracy of predicted
      marginals, taking into account both model and inference approximations at
      training time. Experiments on imaging problems suggest marginalization-based
      learning performs better than likelihood-based approximations on difficult
      problems where the model being fit is approximate in nature. 

PMID- 23969390
TI  - Modeling temporal interactions with interval temporal bayesian networks for
      complex activity recognition.
AB  - Complex activities typically consist of multiple primitive events happening in
      parallel or sequentially over a period of time. Understanding such activities
      requires recognizing not only each individual event but, more importantly,
      capturing their spatiotemporal dependencies over different time intervals. Most
      of the current graphical model-based approaches have several limitations. First,
      time--sliced graphical models such as hidden Markov models (HMMs) and dynamic
      Bayesian networks are typically based on points of time and they hence can only
      capture three temporal relations: precedes, follows, and equals. Second, HMMs are
      probabilistic finite-state machines that grow exponentially as the number of
      parallel events increases. Third, other approaches such as syntactic and
      description-based methods, while rich in modeling temporal relationships, do not
      have the expressive power to capture uncertainties. To address these issues, we
      introduce the interval temporal Bayesian network (ITBN), a novel graphical model
      that combines the Bayesian Network with the interval algebra to explicitly model
      the temporal dependencies over time intervals. Advanced machine learning methods
      are introduced to learn the ITBN model structure and parameters. Experimental
      results show that by reasoning with spatiotemporal dependencies, the proposed
      model leads to a significantly improved performance when modeling and recognizing
      complex activities involving both parallel and sequential events. 

PMID- 23969391
TI  - Multiview face detection and registration requiring minimal manual intervention.
AB  - Most face recognition systems require faces to be detected and localized a
      priori. In this paper, an approach to simultaneously detect and localize multiple
      faces having arbitrary views and different scales is proposed. The main
      contribution of this paper is the introduction of a face constellation, which
      enables multiview face detection and localization. In contrast to other multiview
      approaches that require many manually labeled images for training, the proposed
      face constellation requires only a single reference image of a face containing
      two manually indicated reference points for initialization. Subsequent training
      face images from arbitrary views are automatically added to the constellation
      (registered to the reference image) based on finding the correspondences between
      distinctive local features. Thus, the key advantage of the proposed scheme is the
      minimal manual intervention required to train the face constellation. We also
      propose an approach to identify distinctive correspondence points between pairs
      of face images in the presence of a large amount of false matches. To detect and
      localize multiple faces with arbitrary views, we then propose a probabilistic
      classifier-based formulation to evaluate whether a local feature cluster
      corresponds to a face. Experimental results conducted on the FERET, CMU, and FDDB
      datasets show that our proposed approach has better performance compared to the
      state-of-the-art approaches for detecting faces with arbitrary pose. 

PMID- 23969392
TI  - Nonlinear camera response functions and image deblurring: theoretical analysis
      and practice.
AB  - This paper investigates the role that nonlinear camera response functions (CRFs)
      have on image deblurring. We present a comprehensive study to analyze the effects
      of CRFs on motion deblurring. In particular, we show how nonlinear CRFs can cause
      a spatially invariant blur to behave as a spatially varying blur. We prove that
      such nonlinearity can cause large errors around edges when directly applying
      deconvolution to a motion blurred image without CRF correction. These errors are
      inevitable even with a known point spread function (PSF) and with state-of-the
      art regularization-based deconvolution algorithms. In addition, we show how CRFs
      can adversely affect PSF estimation algorithms in the case of blind
      deconvolution. To help counter these effects, we introduce two methods to
      estimate the CRF directly from one or more blurred images when the PSF is known
      or unknown. Our experimental results on synthetic and real images validate our
      analysis and demonstrate the robustness and accuracy of our approaches. 

PMID- 23969393
TI  - Stereo seam carving a geometrically consistent approach.
AB  - Image retargeting algorithms attempt to adapt the image content to the screen
      without distorting the important objects in the scene. Existing methods address
      retargeting of a single image. In this paper, we propose a novel method for
      retargeting a pair of stereo images. Naively retargeting each image independently
      will distort the geometric structure and hence will impair the perception of the
      3D structure of the scene. We show how to extend a single image seam carving to
      work on a pair of images. Our method minimizes the visual distortion in each of
      the images as well as the depth distortion. A key property of the proposed method
      is that it takes into account the visibility relations between pixels in the
      image pair (occluded and occluding pixels). As a result, our method guarantees,
      as we formally prove, that the retargeted pair is geometrically consistent with a
      feasible 3D scene, similar to the original one. Hence, the retargeted stereo pair
      can be viewed on a stereoscopic display or further processed by any computer
      vision algorithm. We demonstrate our method on a number of challenging indoor and
      outdoor stereo images. 

PMID- 23969394
TI  - Two cloud-based cues for estimating scene structure and camera calibration.
AB  - We describe algorithms that use cloud shadows as a form of stochastically
      structured light to support 3D scene geometry estimation. Taking video captured
      from a static outdoor camera as input, we use the relationship of the time series
      of intensity values between pairs of pixels as the primary input to our
      algorithms. We describe two cues that relate the 3D distance between a pair of
      points to the pair of intensity time series. The first cue results from the fact
      that two pixels that are nearby in the world are more likely to be under a cloud
      at the same time than two distant points. We describe methods for using this cue
      to estimate focal length and scene structure. The second cue is based on the
      motion of cloud shadows across the scene; this cue results in a set of linear
      constraints on scene structure. These constraints have an inherent ambiguity,
      which we show how to overcome by combining the cloud motion cue with the spatial
      cue. We evaluate our method on several time lapses of real outdoor scenes. 

PMID- 23969395
TI  - Joint histogram-based cost aggregation for stereo matching.
AB  - This paper presents a novel method for performing efficient cost aggregation in
      stereo matching. The cost aggregation problem is reformulated from the
      perspective of a histogram, giving us the potential to reduce the complexity of
      the cost aggregation in stereo matching significantly. Differently from previous
      methods which have tried to reduce the complexity in terms of the size of an
      image and a matching window, our approach focuses on reducing the computational
      redundancy that exists among the search range, caused by a repeated filtering for
      all the hypotheses. Moreover, we also reduce the complexity of the window-based
      filtering through an efficient sampling scheme inside the matching window. The
      tradeoff between accuracy and complexity is extensively investigated by varying
      the parameters used in the proposed method. Experimental results show that the
      proposed method provides high-quality disparity maps with low complexity and
      outperforms existing local methods. This paper also provides new insights into
      complexity-constrained stereo-matching algorithm design. 

PMID- 23969396
TI  - Minimum near-convex shape decomposition.
AB  - Shape decomposition is a fundamental problem for part-based shape representation.
      We propose the minimum near-convex decomposition (MNCD) to decompose arbitrary
      shapes into minimum number of "near-convex" parts. The near-convex shape
      decomposition is formulated as a discrete optimization problem by minimizing the
      number of nonintersecting cuts. Two perception rules are imposed as constraints
      into our objective function to improve the visual naturalness of the
      decomposition. With the degree of near-convexity a user-specified parameter, our
      decomposition is robust to local distortions and shape deformation. The
      optimization can be efficiently solved via binary integer linear programming.
      Both theoretical analysis and experiment results show that our approach
      outperforms the state-of-the-art results without introducing redundant parts and
      thus leads to robust shape representation. 

PMID- 23969397
TI  - Monotonicity and error type differentiability in performance measures for target
      detection and tracking in video.
AB  - There exists an abundance of systems and algorithms for multiple target detection
      and tracking in video, and many measures for evaluating the quality of their
      output have been proposed. The contribution of this paper lies in the following:
      first, it argues that such performance measures should have two fundamental
      properties--monotonicity and error type differentiability; second, it shows that
      the recently proposed measures do not have either of these properties and are,
      thus, less usable; third, it composes a set of simple measures, partly built on
      common practice, that does have these properties. The informativeness of the
      proposed set of performance measures is demonstrated through their application on
      face detection and tracking results. 

PMID- 23969398
TI  - Landscape and seasonal factors influence Salmonella and Campylobacter prevalence
      in a rural mixed use watershed.
AB  - Salmonella and Campylobacter prevalence in stream networks of the Satilla River
      Basin (SRB) were monitored monthly from August 2007 to August 2009 to study
      relationships between these pathogens and land use, presence of poultry houses
      and wastewater treatment plant (WWTP) discharge. Salmonella and Campylobacter
      were detected at all 10 stream sites and the three sites at the sole wastewater
      treatment plant (WWTP) in the study area. In all, 43% (129/299) and 62% (96/156)
      of samples were positive for Salmonella and Campylobacter, respectively, with
      detection frequency increasing in downstream sites with more poultry production
      and influence of WWTP discharge. Both Salmonella and Campylobacter detection
      frequencies were positively associated with the number of poultry houses in the
      subwatersheds, but agricultural land use as a proportion of the watershed was not
      a significant predictor of either pathogen. Fecal indicator bacterial levels were
      assessed and evaluated for their ability to predict the presence of pathogens. Of
      those examined, enterococci was most predictive; of the 129 samples positive for
      Salmonella, 88% (113/129) were detected when enterococci were above EPA single
      sample threshold (61 CFU 100 ml(-1)); and of the 96 samples positive for
      Campylobacter, 90% (86/96) were detected when enterococci levels exceeded this
      level. Comparatively, Escherichia coli concentrations were above EPA single
      sample thresholds in 38% (49/129) of the positive Salmonella samples. Detection
      of the pathogens throughout the watershed indicated that there was potential for
      waterborne transmission especially in downstream areas that were more likely to
      have recreational users.

PMID- 23969399
TI  - TiO2 nanoparticles aggregation and disaggregation in presence of alginate and
      Suwannee River humic acids. pH and concentration effects on nanoparticle
      stability.
AB  - The behavior of manufactured TiO2 nanoparticles is studied in a systematic way in
      presence of alginate and Suwannee River humic acids at variable concentrations.
      TiO2 nanoparticles aggregation, disaggregation and stabilization are investigated
      using dynamic light scattering and electrophoretic experiments allowing the
      measurement of z-average hydrodynamic diameters and zeta potential values.
      Stability of the TiO2 nanoparticles is discussed by considering three pH
      dependent electrostatic scenarios. In the first scenario, when pH is below the
      TiO2 nanoparticle point of zero charge, nanoparticles exhibit a positively
      charged surface whereas alginate and Suwannee River humic acids are negatively
      charged. Fast adsorption at the TiO2 nanoparticles occurs, promotes surface
      charge neutralization and aggregation. By increasing further alginate and
      Suwannee River humic acids concentrations charge inversion and stabilization of
      TiO2 nanoparticles are obtained. In the second electrostatic scenario, at the
      surface charge neutralization pH, TiO2 nanoparticles are rapidly forming
      aggregates. Adsorption of alginate and Suwannee River humic acids on aggregates
      leads to their partial fragmentation. In the third electrostatic scenario, when
      nanoparticles, alginate and Suwannee River humic acids are negatively charged,
      only a small amount of Suwannee River humic acids is adsorbed on TiO2
      nanoparticles surface. It is found that the fate and behavior of individual and
      aggregated TiO2 nanoparticles in presence of environmental compounds are mainly
      driven by the complex interplay between electrostatic attractive and repulsive
      interactions, steric and van der Waals interactions, as well as concentration
      ratio. Results also suggest that environmental aquatic concentration ranges of
      humic acids and biopolymers largely modify the stability of aggregated or
      dispersed TiO2 nanoparticles. 

PMID- 23969400
TI  - Life cycle assessment applied to wastewater treatment: state of the art.
AB  - Life cycle assessment (LCA) is a technique to quantify the impacts associated
      with a product, service or process from cradle-to-grave perspective. Within the
      field of wastewater treatment (WWT) LCA was first applied in the 1990s. In the
      pursuit of more environmentally sustainable WWT, it is clear that LCA is a
      valuable tool to elucidate the broader environmental impacts of design and
      operation decisions. With growing interest from utilities, practitioners, and
      researchers in the use of LCA in WWT systems, it is important to make a review of
      what has been achieved and describe the challenges for the forthcoming years.
      This work presents a comprehensive review of 45 papers dealing with WWT and LCA.
      The analysis of the papers showed that within the constraints of the ISO
      standards, there is variability in the definition of the functional unit and the
      system boundaries, the selection of the impact assessment methodology and the
      procedure followed for interpreting the results. The need for stricter adherence
      to ISO methodological standards to ensure quality and transparency is made clear
      and emerging challenges for LCA applications in WWT are discussed, including: a
      paradigm shift from pollutant removal to resource recovery, the adaptation of LCA
      methodologies to new target compounds, the development of regional factors, the
      improvement of the data quality and the reduction of uncertainty. Finally, the
      need for better integration and communication with decision-makers is
      highlighted. 

PMID- 23969401
TI  - Bifunctional resin-ZVI composites for effective removal of arsenite through
      simultaneous adsorption and oxidation.
AB  - Bifunctional resin-supported nanosized zero-valent iron (N-S-ZVI) composite was
      developed by combining the oxidation properties of nZVI/O2 with adsorption
      features of iron oxides and anion-exchange resin N-S. In batch culture
      experiments, N-S and the N-S-ZVI composite were examined for As(III) and As(V).
      The results reveal that ZVI in the composite played a key role in enhancing
      As(III) removal. The N-S-ZVI composites could oxidize more toxic As(III) to less
      toxic As(V) with high efficiency under ambient conditions without the need of
      noble metals. At the same time, the oxidized As(V) could be effectively removed
      by adsorption onto the surface of composites. The mechanisms for the oxidation of
      As(III) to As(V) and the simultaneous removal of As(V) are proposed. In order to
      investigate the potential performance of N-S-ZVI in practical use, the effects of
      solution pH and coexisting anions on arsenite removal and on fixed-bed column
      treatment of simulated waters were studied. All the results indicated that the
      bifunctional composites have a great potential for As(III) removal from
      contaminated waters. 

PMID- 23969402
TI  - Attitudes about palliative care: a comparison of pediatric critical care and
      oncology providers.
AB  - INTRODUCTION: Pediatric critical care and oncology providers care for patients
      who have life-threatening or serious illness, yet they receive little palliative
      care education. OBJECTIVE: Compare oncology and critical care providers'
      attitudes regarding palliative care. METHODS: An electronic survey assessed
      respondents' opinions of whether, when, and why palliative care should be
      utilized. RESULTS: Response rate was 49%. Critical care physicians were more
      likely to incorporate palliative care for psychosocial support; oncologists for
      symptom control. Those with palliative care education were more likely to involve
      in palliative care, did so earlier and for reasons other than end-of-life
      planning. CONCLUSIONS: Oncology and critical care providers utilized palliative
      care for different reasons.

PMID- 23969403
TI  - Letter to the editor on harnessing complex emergent metaphors for effective
      communication in palliative care: a multimodal perceptual analysis of hospice
      patients' reports of transcendence experiences.

PMID- 23969405
TI  - Assessing early growth and adiposity: report from an EarlyNutrition Academy
      workshop.
AB  - This report provides a summary of a workshop organised by the European Commission
      funded EarlyNutrition Project and the EarlyNutrition Academy. Accurate and
      reliable methods to assess body composition are needed in research on prenatal
      and early post-natal influences of nutrition on later health because common
      surrogate measures of maternal and offspring adiposity (body fat content), such
      as body mass index (BMI), have relatively poor predictive power for the risk of
      later disease. The key goals of the workshop were to discuss approaches to assess
      growth and body composition from pregnancy to adolescence, to summarise
      conclusions and to prepare a framework for research in the EarlyNutrition
      Project. The participants concluded that there is a pressing need to harmonise
      the methodologies for assessing body composition, recognising that each has
      advantages and limitations. Essential core measurements across studies assessing
      early growth and body composition were identified, including weight, length, BMI,
      waist and mid-upper arm circumference, subscapular and triceps skinfold
      thicknesses, and bioelectrical impedance analysis. In research settings with
      access to more sophisticated technologies, additional methods could include dual
      energy X-ray absorptiometry, peripheral quantitative computed tomography,
      ultrasound assessment of regional body fat, magnetic resonance imaging (MRI), air
      displacement plethysmography (ADP), and deuterium dilution. These provide richer
      data to answer research questions in greater depth but also increase costs. Where
      overall whole-body composition is the primary outcome measure, ADP or tracer
      dilution should be used whenever possible. Where regional distribution of body
      fat is of greater interest, an imaging technique such as MRI is preferred. 

PMID- 23969404
TI  - Stevens-Johnson syndrome induced by sorafenib for metastatic renal cell
      carcinoma.
AB  - Sorafenib is an orally administered active multikinase inhibitor for metastatic
      renal cell carcinoma that is now considered a standard agent. Skin toxicity, such
      as hand-foot skin reaction, is one of the frequent adverse effects of sorafenib.
      On the other hand, sorafenib-induced erythema multiforme is very rare, and
      Stevens-Johnson syndrome and toxic epidermal necrolysis induced by sorafenib have
      not been reported. We report the first case of Stevens-Johnson syndrome caused by
      sorafenib for metastatic renal cell carcinoma.

PMID- 23969406
TI  - Complex resistivity signatures of ethanol biodegradation in porous media.
AB  - Numerous adverse effects are associated with the accidental release of ethanol
      (EtOH) and its persistence in the subsurface. Geophysical techniques may permit
      non-invasive, real time monitoring of microbial degradation of hydrocarbon. We
      performed complex resistivity (CR) measurements in conjunction with geochemical
      data analysis on three microbial-stimulated and two control columns to
      investigate changes in electrical properties during EtOH biodegradation processes
      in porous media. A Debye Decomposition approach was applied to determine the
      chargeability (m), normalized chargeability (m(n)) and time constant (tau) of the
      polarization magnitude and relaxation length scale as a function of time. The CR
      responses showed a clear distinction between the bioaugmented and control columns
      in terms of real (sigma') and imaginary (sigma") conductivity, phase (phi) and
      apparent formation factor (F(app)). Unlike the control columns, a substantial
      decrease in sigma' and increase in F(app) occurred at an early time (within 4
      days) of the experiment for all three bioaugmented columns. The observed decrease
      in sigma' is opposite to previous studies on hydrocarbon biodegradation. These
      columns also exhibited increases in phi (up to ~9 mrad) and sigma" (up to two
      order of magnitude higher) 5 weeks after microbial inoculation. Variations in m
      and m(n) were consistent with temporal changes in phi and sigma" responses,
      respectively. Temporal geochemical changes and high resolution scanning electron
      microscopy imaging corroborated the CR findings, thus indicating the sensitivity
      of CR measurements to EtOH biodegradation processes. Our results offer insight
      into the potential application of CR measurements for long-term monitoring of
      biogeochemical and mineralogical changes during intrinsic and induced EtOH
      biodegradation in the subsurface.

PMID- 23969408
TI  - Malnutrition Forum introduction.

PMID- 23969407
TI  - Prognostic factors and survival after resection of colorectal liver metastasis in
      the era of preoperative chemotherapy: an 11-year single-centre study.
AB  - INTRODUCTION: A variety of factors have been identified in the literature which
      influence survival following resection of colorectal liver metastases (CRLM).
      Much of this literature is historical, and its relevance to contemporary practice
      is not known. The aim of this study was to identify those factors which influence
      survival during the era of preoperative chemotherapy in patients undergoing
      resection of CRLM in a UK centre. METHODS: All patients having liver resection
      for CRLM during an 11-year period up to 2011 were identified from a prospectively
      maintained database. Prognostic factors analysed included tumour size (>=5 or <5
      cm), lymph node status of the primary tumour, margin positivity (R1; <1 mm), neo
      adjuvant chemotherapy (for liver), tumour differentiation, number of liver
      metastases (>=4), preoperative carcinoembryonic antigen (CEA; >=200 ng/ml) and
      whether metastases were synchronous (i.e. diagnosed within 12 months of
      colorectal resection) or metachronous to the primary tumour. Overall survival
      (OS) was compared using Kaplan-Meier plots and a log rank test for significance.
      Multivariate analysis was performed using a Cox regression model. Statistical
      analysis was performed in SPSS v19, and p < 0.05 was considered to be
      significant. RESULTS: 432 patients underwent resection of CRLM during this period
      (67% male; mean age 64.5 years), and of these, 54 (13.5%) had re-resections. The
      overall 5-year survival in this series was 43% with an actuarial 10-year survival
      of 40%. A preoperative CEA >=200 ng/ml was present in 10% of patients and was
      associated with a poorer 5-year OS (24 vs. 45%; p < 0.001). A positive resection
      margin <1 mm was present in 16% of patients, and this had a negative impact on 5
      year OS (15 vs. 47%; p < 0.001). Tumour differentiation, number, biliary or
      vascular invasion, size, relationship to primary disease, nodal status of the
      primary disease or the use of neo-adjuvant chemotherapy had no impact on OS.
      Multivariate analysis identified only the presence of a positive resection margin
      (OR 1.75; p < 0.05) and a preoperative CEA >=200 ng/ml (OR 1.88; p < 0.01) as
      independent predictors of poor OS. CONCLUSION: Despite the wide variety of
      prognostic factors reported in the literature, this study was only able to
      identify a preoperative CEA >=200 ng/ml and the presence of tumour within 1 mm of
      the resection margin as being of value in predicting survival. These variables
      are likely to identify patients who may benefit from intensive follow-up to
      enable early aggressive treatment of recurrent disease.

PMID- 23969409
TI  - Managing postacute malnutrition (undernutrition) risk.
AB  - Although a direct correlation between poor nutrition status and increased risk of
      readmission has yet to be established, it is reasonable to assume that patients
      who are identified as undernourished while hospitalized would be "at increased
      risk of adverse outcomes" following discharge. Also, the evidence that links
      nonadherence to dietary prescriptions after discharge, with increased
      readmissions in patients with heart failure (HF), is fairly robust. Nutrition
      screening prior to discharge should be mandated, just as it is at admission.
      However, the criteria to assess a patient's ability to adequately and
      appropriately nourish themselves after discharge are very different from those
      used to diagnose and treat malnutrition on admission or during a hospital stay.
      The U.S. healthcare environment germane to the readmissions rates policy that was
      adopted for implementation in October 2012 by the Centers for Medicare & Medicaid
      Services is characterized. Factors critical to the successful development and
      implementation of a post-acute nutrition care plan are described. Nutrition
      related contributors to readmissions in HF are delineated. Transitional care
      models that could be adapted to enhance nutrition care plan efficacy are
      identified, as is the need to adopt a multidisciplinary approach to nutrition in
      transitional care that includes care coordination and routine follow-up. An
      evidence-based systematic approach to determine those patients in whom palliative
      vs restorative nutrition care is appropriate needs to be developed. 

PMID- 23969410
TI  - Addressing malnutrition in hospitalized adults.
AB  - Established guidelines and standardized protocols exist to assist clinicians in
      effectively addressing disease-related malnutrition in hospitalized adults. The
      goals of this treatment vary according to the disease state and the severity of
      the malnutrition. In starvation-related malnutrition, the goal of nutrition
      therapy is to restore healthy levels of lean body mass and body fat. For chronic
      disease-related malnutrition, the goals of treatment are to maintain and improve
      lean body mass and body fat. In acute-disease-related malnutrition, the goals of
      nutrition therapy are to support vital organ function and preserve the host
      response through the acute episode. The success of addressing malnutrition in
      hospitalized patients depends not just on the nutrition therapy selected, but
      also on the timely and appropriate application of guidelines and protocols by the
      clinicians dedicated to caring for malnourished patients. Coordination of
      nutrition care among providers is highly desirable, and usually includes a
      multidisciplinary team of clinicians typically comprising a physician, nurse,
      dietitian, and pharmacist. For greatest success, this attention to recognizing
      and addressing malnutrition begins at admission and continues beyond discharge to
      the community. When addressing malnutrition in hospitalized patients, oral
      feeding through diet enrichment or oral nutrition supplementation (ONS) is the
      first line of defense. ONS has consistently been demonstrated to provide
      nutrition, clinical, functional, and economic benefits to malnourished patients
      in both individual trials and meta-analyses. In an era when the cost of
      healthcare is rising as the population ages, addressing malnutrition in
      hospitalized patients is an important priority. 

PMID- 23969411
TI  - Recognizing malnutrition in adults: definitions and characteristics, screening,
      assessment, and team approach.
AB  - Appropriate recognition of malnutrition in adults requires knowledge of screening
      and assessment methodologies. An appreciation for the contributions of
      inflammation has resulted in a new etiology-based approach to defining
      malnutrition syndromes. The Academy of Nutrition and Dietetics and the American
      Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) have published a
      consensus document that extends this approach to describe characteristics for the
      identification and documentation of malnutrition in adults. Nutrition screening
      tools are used to identify patients at nutrition risk and those who are likely to
      benefit from further assessment and intervention. Nutrition assessment serves to
      guide appropriate intervention. A systematic approach to nutrition assessment
      that supports the new diagnostic scheme and criteria from the Academy and
      A.S.P.E.N. has recently been presented. Since screening delays and failures in
      the diagnosis and management of malnutrition are all too common, a
      multidisciplinary team approach is recommended to promote improved communication
      and quality of care. 

PMID- 23969412
TI  - Assembly of trimeric polyoxovanadate aggregates based on [MnV13O38]7- building
      blocks and lanthanide cations.
AB  - Three trimeric polyoxovanadate based on 1:13 anions [MnV13O38](7-) with
      lanthanide cations Ln(3+) (Ln = La, Ce and Nd) and pyridine-3-carboxylic acid:
      HK3{[Ln(H2O)4]6[MnV13O38]3(SO4)2}.3(C6H6NO2).nH2O (Ln = La 1, Nd 3; n = 33 for 1,
      20 for 3), H(2.5)K(1.5){[Ce(H2O)4]6[MnV13O38]3(SO4)2}.3(C6H6NO2).20.5H2O (2)
      (C6H5NO2 = pyridine-3-carboxylic acid) have been synthesized and characterized by
      elemental analysis, IR spectroscopy, UV spectroscopy, TG analysis, XPRD,
      electrochemical analyses, magnetism and single-crystal X-ray diffraction.
      Compounds 1-3 are isostructural and crystallized in the hexagonal system, space
      group P6(3)/m. Compounds 1-3 contain an unusual trimeric polyoxoanion
      [{Ln2MnV13O38}3(SO4)2](7-), representing the first polyoxovanadate-based trimeric
      aggregate with rare earth ions. The electrochemical and electrocatalytic
      properties of the compounds have been investigated. Magnetic studies indicate
      that antiferromagnetic interactions exist in the compounds.

PMID- 23969413
TI  - Highly hydrophilic and insulating fluorinated reduced graphene oxide.
AB  - A facile method for the synthesis of highly fluorinated reduced graphene oxide
      from graphene oxide using BF3-OEt2 solution and alkylthiol/alkylamine on the Gram
      scale has been described using a detailed mechanism. The maximum fluorination was
      as high as 38 wt% and the fluorinated reduced graphene oxide produced has great
      wettability and high insulating properties. 

PMID- 23969414
TI  - One antitoxin--two functions: SR4 controls toxin mRNA decay and translation.
AB  - Type I toxin-antitoxin systems encoded on bacterial chromosomes became the focus
      of research during the past years. However, little is known in terms of
      structural requirements, kinetics of interaction with their targets and
      regulatory mechanisms of the antitoxin RNAs. Here, we present a combined in vitro
      and in vivo analysis of the bsrG/SR4 type I toxin-antitoxin system from Bacillus
      subtilis. The secondary structures of SR4 and bsrG mRNA and of the SR4/bsrG RNA
      complex were determined, apparent binding rate constants calculated and
      functional segments required for complex formation narrowed down. The initial
      contact between SR4 and its target was shown to involve the SR4 terminator loop
      and loop 3 of bsrG mRNA. Additionally, a contribution of the stem of SR4 stem
      loop 3 to target binding was found. On SR4/bsrG complex formation, a 4 bp double
      stranded region sequestering the bsrG Shine Dalgarno (SD) sequence was extended
      to 8 bp. Experimental evidence was obtained that this extended region caused
      translation inhibition of bsrG mRNA. Therefore, we conclude that SR4 does not
      only promote degradation of the toxin mRNA but also additionally inhibit its
      translation. This is the first case of a dual-acting antitoxin RNA. 

PMID- 23969415
TI  - Aminoacylation and translational quality control strategy employed by leucyl-tRNA
      synthetase from a human pathogen with genetic code ambiguity.
AB  - Aminoacyl-tRNA synthetases should ensure high accuracy in tRNA aminoacylation.
      However, the absence of significant structural differences between amino acids
      always poses a direct challenge for some aminoacyl-tRNA synthetases, such as
      leucyl-tRNA synthetase (LeuRS), which require editing function to remove mis
      activated amino acids. In the cytoplasm of the human pathogen Candida albicans,
      the CUG codon is translated as both Ser and Leu by a uniquely evolved
      CatRNA(Ser)(CAG). Its cytoplasmic LeuRS (CaLeuRS) is a crucial component for CUG
      codon ambiguity and harbors only one CUG codon at position 919. Comparison of the
      activity of CaLeuRS-Ser(919) and CaLeuRS-Leu(919) revealed yeast LeuRSs have a
      relaxed tRNA recognition capacity. We also studied the mis-activation and editing
      of non-cognate amino acids by CaLeuRS. Interestingly, we found that CaLeuRS is
      naturally deficient in tRNA-dependent pre-transfer editing for non-cognate
      norvaline while displaying a weak tRNA-dependent pre-transfer editing capacity
      for non-cognate alpha-amino butyric acid. We also demonstrated that post-transfer
      editing of CaLeuRS is not tRNA(Leu) species-specific. In addition, other
      eukaryotic but not archaeal or bacterial LeuRSs were found to recognize
      CatRNA(Ser)(CAG). Overall, we systematically studied the aminoacylation and
      editing properties of CaLeuRS and established a characteristic LeuRS model with
      naturally deficient tRNA-dependent pre-transfer editing, which increases LeuRS
      types with unique editing patterns. 

PMID- 23969416
TI  - Competitive superhelical transitions involving cruciform extrusion.
AB  - A DNA molecule under negative superhelical stress becomes susceptible to
      transitions to alternate structures. The accessible alternate conformations
      depend on base sequence and compete for occupancy. We have developed a method to
      calculate equilibrium distributions among the states available to such systems,
      as well as their average thermodynamic properties. Here we extend this approach
      to include superhelical cruciform extrusion at both perfect and imperfect
      inverted repeat (IR) sequences. We find that short IRs do not extrude cruciforms,
      even in the absence of competition. But as the length of an IR increases, its
      extrusion can come to dominate both strand separation and B-Z transitions.
      Although many IRs are present in human genomic DNA, we find that extrusion
      susceptible ones occur infrequently. Moreover, their avoidance of transcription
      start sites in eukaryotes suggests that cruciform formation is rarely involved in
      mechanisms of gene regulation. We examine a set of clinically important
      chromosomal translocation breakpoints that occur at long IRs, whose rearrangement
      has been proposed to be driven by cruciform extrusion. Our results show that the
      susceptibilities of these IRs to cruciform formation correspond closely with
      their observed translocation frequencies. 

PMID- 23969417
TI  - Opposing roles for 53BP1 during homologous recombination.
AB  - Although DNA non-homologous end-joining repairs most DNA double-strand breaks
      (DSBs) in G2 phase, late repairing DSBs undergo resection and repair by
      homologous recombination (HR). Based on parallels to the situation in G1 cells,
      previous work has suggested that DSBs that undergo repair by HR predominantly
      localize to regions of heterochromatin (HC). By using H3K9me3 and H4K20me3 to
      identify HC regions, we substantiate and extend previous evidence, suggesting
      that HC-DSBs undergo repair by HR. Next, we examine roles for 53BP1 and BRCA1 in
      this process. Previous studies have shown that 53BP1 is pro-non-homologous end
      joining and anti-HR. Surprisingly, we demonstrate that in G2 phase, 53BP1 is
      required for HR at HC-DSBs with its role being to promote phosphorylated KAP-1
      foci formation. BRCA1, in contrast, is dispensable for pKAP-1 foci formation but
      relieves the barrier caused by 53BP1. As 53BP1 is retained at irradiation-induced
      foci during HR, we propose that BRCA1 promotes displacement but retention of
      53BP1 to allow resection and any necessary HC modifications to complete HR. In
      contrast to this role for 53BP1 in HR in G2 phase, we show that it is dispensable
      for HR in S phase, where HC regions are likely relaxed during replication. 

PMID- 23969418
TI  - Angiotensin receptor blockers are associated with reduced fibrosis and
      interleukin-6 expression in calcific aortic valve disease.
AB  - BACKGROUND: Calcific aortic valve disease (CAVD) is a chronic disorder
      characterized by the mineralization of the aortic valve and involving fibrosis.
      OBJECTIVES: In this work we sought to determine if the fibrotic component of the
      remodeling process of CAVD was related to the use of angiotensin-converting
      enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARBs). METHODS: In
      477 patients with CAVD, the aortic valve was examined by histology. A
      semiquantitative score of fibrosis was generated and associations with
      clinical/cardiometabolic variables examined. In a subset of 103 patients the
      aortic valve was available to study the infiltration by inflammatory cells and
      expression of interleukin-6 (IL-6) by quantitative real-time PCR. RESULTS: The
      fibrosis score of the aortic valve was independently related to the hemodynamic
      severity of CAVD measured by echocardiography. The fibrotic score of the aortic
      valve was also related to the expression of IL-6. The use of ARBs but not of ACEi
      was associated with a lower fibrosis score of the aortic valve even after
      correction for covariates. In addition, patients under ARBs had lower aortic
      valve inflammation and expression of IL-6. CONCLUSIONS: These findings suggest
      that ARBs may alter the fibrotic process of the aortic valve in CAVD, possibly by
      lowering tissue inflammation.

PMID- 23969420
TI  - Brain region- and sex-specific modulation of mitochondrial glucocorticoid
      receptor phosphorylation in fluoxetine treated stressed rats: effects on energy
      metabolism.
AB  - Antidepressants affect glucocorticoid receptor (GR) functioning partly through
      modulation of its phosphorylation but their effects on mitochondrial GR have
      remained undefined. We investigated the ability of chronic fluoxetine treatment
      to affect chronic stress-induced changes of mitochondrial GR and its
      phosphoisoforms (pGRs) in the prefrontal cortex and hippocampus of female and
      male rats. Since mitochondrial GR regulates oxidative phosphorylation, expression
      of mitochondrial-encoded subunits of cytochrome (cyt) c oxidase and its activity
      were also investigated. Chronic stress caused accumulation of the GR in
      mitochondria of female prefrontal cortex, while the changes in the hippocampus
      were sex-specific at the levels of pGRs. Expression of mitochondrial COXs genes
      corresponded to chronic stress-modulated mitochondrial GR in both tissues of both
      genders and to cyt c oxidase activity in females. Moreover, the metabolic
      parameters in stressed animals were affected by fluoxetine therapy only in the
      hippocampus. Namely, fluoxetine effects on mitochondrial COXs and cyt c oxidase
      activity in the hippocampus seem to be conveyed through pGR232 in females, while
      in males this likely occurs through other mechanisms. In summary, sex-specific
      regulation of cyt c oxidase by the stress and antidepressant treatment and its
      differential convergence with mitochondrial GR signaling in the prefrontal cortex
      and hippocampus could contribute to clarification of sex-dependent vulnerability
      to stress-related disorders and sex-specific clinical impact of antidepressants. 

PMID- 23969419
TI  - Isolation and mutational analysis of circulating tumor cells from lung cancer
      patients with magnetic sifters and biochips.
AB  - Detection and characterization of circulating tumor cells (CTCs) may reveal
      insights into the diagnosis and treatment of malignant disease. Technologies for
      isolating CTCs developed thus far suffer from one or more limitations, such as
      low throughput, inability to release captured cells, and reliance on expensive
      instrumentation for enrichment or subsequent characterization. We report a
      continuing development of a magnetic separation device, the magnetic sifter,
      which is a miniature microfluidic chip with a dense array of magnetic pores. It
      offers high efficiency capture of tumor cells, labeled with magnetic
      nanoparticles, from whole blood with high throughput and efficient release of
      captured cells. For subsequent characterization of CTCs, an assay, using a
      protein chip with giant magnetoresistive nanosensors, has been implemented for
      mutational analysis of CTCs enriched with the magnetic sifter. The use of these
      magnetic technologies, which are separate devices, may lead the way to routine
      preparation and characterization of "liquid biopsies" from cancer patients. 

PMID- 23969422
TI  - Comparing predictors of conversion to Alzheimer's disease using the disease state
      index.
AB  - BACKGROUND: The Disease State Index (DSI) is a method which interprets data
      originating from multiple different sources, assisting the clinician in the
      diagnosis and follow-up of dementia diseases. OBJECTIVE: We compared the
      differences in accuracy in differentiating stable mild cognitive impairment (S
      MCI) and progressive MCI (P-MCI) obtained from different data combinations using
      the DSI. METHODS: We investigated 212 cases with S-MCI and 165 cases with P-MCI
      from the Alzheimer's Disease Neuroimaging Initiative cohort. Data from
      neuropsychological tests, cerebrospinal fluid, apolipoprotein E (APOE) genotype,
      magnetic resonance imaging (MRI) and positron emission tomography (PET) were
      included. RESULTS: The combination of all parameters gave the highest accuracy
      (accuracy 0.70, sensitivity 0.71, specificity 0.68). In the different categories,
      neuropsychological tests (0.65, 0.65, 0.65) and hippocampal volumetry (0.66,
      0.66, 0.66) achieved the highest accuracy. CONCLUSION: In addition to
      neuropsychological testing, MRI is recommended to be included for differentiating
      S-MCI from P-MCI. APOE genotype, CSF and PET may provide some additional
      information.

PMID- 23969421
TI  - Indirect effect of financial strain on daily cortisol output through daily
      negative to positive affect index in the Coronary Artery Risk Development in
      Young Adults Study.
AB  - Daily affect is important to health and has been linked to cortisol. The
      combination of high negative affect and low positive affect may have a bigger
      impact on increasing HPA axis activity than either positive or negative affect
      alone. Financial strain may both dampen positive affect as well as increase
      negative affect, and thus provides an excellent context for understanding the
      associations between daily affect and cortisol. Using random effects mixed
      modeling with maximum likelihood estimation, we examined the relationship between
      self-reported financial strain and estimated mean daily cortisol level (latent
      cortisol variable), based on six salivary cortisol assessments throughout the
      day, and whether this relationship was mediated by greater daily negative to
      positive affect index measured concurrently in a sample of 776 Coronary Artery
      Risk Development in Young Adults (CARDIA) Study participants. The analysis
      revealed that while no total direct effect existed for financial strain on
      cortisol, there was a significant indirect effect of high negative affect to low
      positive affect, linking financial strain to elevated cortisol. In this sample,
      the effects of financial strain on cortisol through either positive affect or
      negative affect alone were not significant. A combined affect index may be a more
      sensitive and powerful measure than either negative or positive affect alone,
      tapping the burden of chronic financial strain, and its effects on biology. 

PMID- 23969424
TI  - Fruit and vegetables: intake and sociodemographic determinants among Portuguese
      mothers.
AB  - BACKGROUND: Fruit and vegetable intake is crucial in health promotion and disease
      prevention. Inadequate intake is found among adult populations worldwide. AIMS:
      To assess fruit and vegetable intake among Portuguese mothers and to examine its
      association with sociodemographic determinants. METHODS: A national cross
      sectional survey was performed in Portugal as part of the Pro Children study.
      Data from self-administrated precoded 24-hour recall and food frequency
      questionnaires answered by 1,853 mothers of 11- to 13-year-old children were
      analyzed. Descriptive analysis of the data was followed by logistic regression to
      assess associations between daily fruit and vegetable intake and sociodemographic
      determinants. RESULTS: The mean fruit and vegetable intake was 221.2 and 170.0
      g/day, respectively. Only 46% of the mothers met the WHO recommendations (>=400 g
      fruit and vegetables/day). Daily fruit intake was significantly higher among
      mothers who live with a spouse/partner, and who belong to a higher social class.
      For vegetables, daily intake was significantly higher among mothers with a higher
      education and social class. CONCLUSIONS: This study shows that the mean intake of
      fruit and vegetables among Portuguese mothers is far below international
      recommendations. Effective strategies to promote fruit and vegetable intake are
      needed, especially for mothers belonging to lower social classes and educational
      levels.

PMID- 23969425
TI  - What is to be done about Russian science?

PMID- 23969437
TI  - Forecasts turn tide on silt.

PMID- 23969438
TI  - Half of 2011 papers now free to read.

PMID- 23969439
TI  - Big horns clash with longevity in sheep.

PMID- 23969440
TI  - Romanian science in free fall.

PMID- 23969441
TI  - US regulation misses some GM crops.

PMID- 23969442
TI  - Stem cells: Egg engineers.

PMID- 23969443
TI  - Medical research: Trial unpredictability yields predictable therapy gains.

PMID- 23969446
TI  - Antibiotics: Support US policy change.

PMID- 23969447
TI  - Panama: Curb indigenous fears of REDD+.

PMID- 23969448
TI  - Fukushima: 'Ecolab' branding insensitive.

PMID- 23969449
TI  - Fukushima: Unpaid soil-research effort.

PMID- 23969450
TI  - Antibiotics: Collect more US data.

PMID- 23969451
TI  - Michael John Morwood (1950-2013).

PMID- 23969452
TI  - Plant biology: Electric defence.

PMID- 23969453
TI  - Astrophysics: Twinkling stars.

PMID- 23969454
TI  - Biotechnology: Programming genomes with light.

PMID- 23969455
TI  - Condensed-matter physics: A solid triple point.

PMID- 23969457
TI  - Ecology: Abundant equals nested.

PMID- 23969458
TI  - Evolutionary biology: A gut feeling for isolation.

PMID- 23969460
TI  - An observational correlation between stellar brightness variations and surface
      gravity.
AB  - Surface gravity is a basic stellar property, but it is difficult to measure
      accurately, with typical uncertainties of 25 to 50 per cent if measured
      spectroscopically and 90 to 150 per cent if measured photometrically.
      Asteroseismology measures gravity with an uncertainty of about 2 per cent but is
      restricted to relatively small samples of bright stars, most of which are giants.
      The availability of high-precision measurements of brightness variations for more
      than 150,000 stars provides an opportunity to investigate whether the variations
      can be used to determine surface gravities. The Fourier power of granulation on a
      star's surface correlates physically with surface gravity: if brightness
      variations on timescales of hours arise from granulation, then such variations
      should correlate with surface gravity. Here we report an analysis of archival
      data that reveals an observational correlation between surface gravity and root
      mean squared brightness variations on timescales of less than eight hours for
      stars with temperatures of 4,500 to 6,750 kelvin, log surface gravities of 2.5 to
      4.5 (cgs units) and overall brightness variations of less than three parts per
      thousand. A straightforward observation of optical brightness variations
      therefore allows a determination of the surface gravity with a precision of
      better than 25 per cent for inactive Sun-like stars at main-sequence to giant
      stages of evolution. 

PMID- 23969459
TI  - GLUTAMATE RECEPTOR-LIKE genes mediate leaf-to-leaf wound signalling.
AB  - Wounded leaves communicate their damage status to one another through a poorly
      understood process of long-distance signalling. This stimulates the distal
      production of jasmonates, potent regulators of defence responses. Using non
      invasive electrodes we mapped surface potential changes in Arabidopsis thaliana
      after wounding leaf eight and found that membrane depolarizations correlated with
      jasmonate signalling domains in undamaged leaves. Furthermore, current injection
      elicited jasmonoyl-isoleucine accumulation, resulting in a transcriptome enriched
      in RNAs encoding key jasmonate signalling regulators. From among 34 screened
      membrane protein mutant lines, mutations in several clade 3 GLUTAMATE RECEPTOR
      LIKE genes (GLRs 3.2, 3.3 and 3.6) attenuated wound-induced surface potential
      changes. Jasmonate-response gene expression in leaves distal to wounds was
      reduced in a glr3.3 glr3.6 double mutant. This work provides a genetic basis for
      investigating mechanisms of long-distance wound signalling in plants and
      indicates that plant genes related to those important for synaptic activity in
      animals function in organ-to-organ wound signalling. 

PMID- 23969461
TI  - Measurement of a solid-state triple point at the metal-insulator transition in
      VO2.
AB  - First-order phase transitions in solids are notoriously challenging to study. The
      combination of change in unit cell shape, long range of elastic distortion and
      flow of latent heat leads to large energy barriers resulting in domain structure,
      hysteresis and cracking. The situation is worse near a triple point, where more
      than two phases are involved. The well-known metal-insulator transition in
      vanadium dioxide, a popular candidate for ultrafast optical and electrical
      switching applications, is a case in point. Even though VO2 is one of the
      simplest strongly correlated materials, experimental difficulties posed by the
      first-order nature of the metal-insulator transition as well as the involvement
      of at least two competing insulating phases have led to persistent controversy
      about its nature. Here we show that studying single-crystal VO2 nanobeams in a
      purpose-built nanomechanical strain apparatus allows investigation of this
      prototypical phase transition with unprecedented control and precision. Our
      results include the striking finding that the triple point of the metallic phase
      and two insulating phases is at the transition temperature, Ttr = Tc, which we
      determine to be 65.0 +/- 0.1  degrees C. The findings have profound implications
      for the mechanism of the metal-insulator transition in VO2, but they also
      demonstrate the importance of this approach for mastering phase transitions in
      many other strongly correlated materials, such as manganites and iron-based
      superconductors. 

PMID- 23969462
TI  - Emergence of structural and dynamical properties of ecological mutualistic
      networks.
AB  - Mutualistic networks are formed when the interactions between two classes of
      species are mutually beneficial. They are important examples of cooperation
      shaped by evolution. Mutualism between animals and plants has a key role in the
      organization of ecological communities. Such networks in ecology have generally
      evolved a nested architecture independent of species composition and latitude;
      specialist species, with only few mutualistic links, tend to interact with a
      proper subset of the many mutualistic partners of any of the generalist species.
      Despite sustained efforts to explain observed network structure on the basis of
      community-level stability or persistence, such correlative studies have reached
      minimal consensus. Here we show that nested interaction networks could emerge as
      a consequence of an optimization principle aimed at maximizing the species
      abundance in mutualistic communities. Using analytical and numerical approaches,
      we show that because of the mutualistic interactions, an increase in abundance of
      a given species results in a corresponding increase in the total number of
      individuals in the community, and also an increase in the nestedness of the
      interaction matrix. Indeed, the species abundances and the nestedness of the
      interaction matrix are correlated by a factor that depends on the strength of the
      mutualistic interactions. Nestedness and the observed spontaneous emergence of
      generalist and specialist species occur for several dynamical implementations of
      the variational principle under stationary conditions. Optimized networks,
      although remaining stable, tend to be less resilient than their counterparts with
      randomly assigned interactions. In particular, we show analytically that the
      abundance of the rarest species is linked directly to the resilience of the
      community. Our work provides a unifying framework for studying the emergent
      structural and dynamical properties of ecological mutualistic networks. 

PMID- 23969464
TI  - "Disentangling nestedness" disentangled.

PMID- 23969465
TI  - James et al. reply.

PMID- 23969466
TI  - Mode of delivery at periviable gestational ages: impact on subsequent
      reproductive outcomes.

PMID- 23969467
TI  - Granule proteases of hematopoietic cells, a family of versatile inflammatory
      mediators - an update on their cleavage specificity, in vivo substrates, and
      evolution.
AB  - Cells from several of the hematopoietic cell lineages including mast cells,
      basophils, neutrophils, cytotoxic T cells, and natural killer (NK) cells store
      proteases at very high levels within their cytoplasmic granules. In mast cells,
      these proteases can account for up to 35% of the total cellular protein, and the
      absolute majority of these belong to the chymotrypsin-related serine protease
      family. A number of very diverse functions have been identified for these
      proteases, including apoptosis induction, blood pressure regulation, inactivation
      of insect and snake toxins, intestinal parasite expulsion, killing of bacteria
      and fungi, induction, mobilization, or degradation of cytokines, and the
      degradation of connective tissue components. A very broad spectrum of primary
      cleavage specificities has also been observed, including chymase, tryptase, asp
      ase, elastase, and met-ase specificities, which highlights the large flexibility
      in the active site of these proteases. Mast cells primarily express chymases and
      tryptases with chymotryptic or tryptic primary cleavage specificities,
      respectively. Neutrophils have several enzymes with chymase, elastase, and
      tryptase specificities. T cells and NK cells express between 5 and 14 different
      granzymes, depending on the species, and these enzymes have tryptase, asp-ase,
      chymase, and met-ase specificities. This review focuses on the appearance of
      these proteases during vertebrate evolution, their primary and extended cleavage
      specificities, and their potential in vivo substrates. The in vivo substrates and
      functions are a particular challenging issue because several of these enzymes
      have a relatively broad specificity and may therefore cleave a wide range of
      different substrates.

PMID- 23969468
TI  - Detection of unknown beta-thalassemia cases from atypical HbA1c chromatograms.

PMID- 23969469
TI  - Category-specific uncertainty modeling in clinical laboratory measurement
      processes.
AB  - BACKGROUND: A statement of measurement uncertainty describes the quality of a
      clinical assay analysis result, and uncertainty models of clinical assays can be
      used to evaluate and optimize laboratory protocols designed to minimize the
      measurement uncertainty associated with an assay. In this study, we propose a
      methodology to lend systematic structure to the uncertainty modeling process.
      METHODS: Clinical laboratory assays are typically classified based on the
      chemical reaction involved, and therefore, based on the assay analysis
      methodology. We use this fact to demonstrate that uncertainty models for assays
      within the same category are structurally identical in all respects except for
      the values of certain model parameters. This is accomplished by building
      uncertainty models for assays belonging to two categories--substrate assays based
      on optical absorbance analysis of endpoint reactions, and ion selective electrode
      (ISE) assays based on potentiometric measurements of electromotive force.
      RESULTS: Uncertainty models for the substrate assays and the ISE assays are
      built, and for each category, a general mathematical framework for the
      uncertainty model is developed. The parameters of the general framework that vary
      from assay to assay for each category are identified and listed. CONCLUSIONS:
      Estimates of measurement uncertainty from the models were compared with estimates
      of uncertainty from quality control data from the clinical laboratory. We
      demonstrate that building a general modeling framework for each assay category
      and plugging in parameter values for each assay is sufficient to generate
      uncertainty models for an assay within a given category.

PMID- 23969470
TI  - Searching for genes involved in hypertension development in special populations:
      children and pre-eclamptic women. Where are we standing now?
AB  - Primary hypertension is a very common disorder particularly in the aging
      population but hypertensive disorders can appear earlier in life, especially when
      obesity and unhealthy lifestyle are present. Also pregnant women can be at risk
      of developing gestational hypertension and/or pre-eclampsia, which causes
      complications in nearly 7% of pregnancies. These "special" populations could be
      regarded as natural models suited to reveal mechanisms of hypertension
      development which are either common to other forms of hypertension, including
      primary hypertension or specific to these populations. Recent studies in the
      field of genetics of primary hypertension have used new powerful tools, such as
      genome-wide association studies (GWAS) and sequencing, but studies about
      hypertension during childhood and in pregnancy have seldom used high-throughput
      technologies and the knowledge in this field comes mostly from the candidate gene
      approach. In this review we summarize some interesting results from genetic
      studies conducted in childhood and adolescence and during pregnancy and underline
      the need to apply modern technologies in these potentially very fruitful
      populations.

PMID- 23969471
TI  - Communities of practice in nursing academia: a growing need to practice what we
      teach.
AB  - Although the community of practice (CoP) concept has been heavily utilized in
      business literature since its inception in the 1990s, it has not been
      significantly featured in nursing research. With student-centered approaches
      increasingly infusing nursing classrooms, including opportunities for
      collaborative learning and the development of student learning communities, it
      may be time to ask: Do we practice what we teach? Nursing academia faces
      challenges related to recruitment and retention, scholarly productivity and
      engagement of new faculty, and increasing demands for collaborative research.
      Challenges, some would argue, that could be addressed through CoPs; a sentiment
      reflected in the recent expansion of nursing CoP literature. What is the current
      state of the application of this concept in nursing academia and what barriers
      present in the promotion and development of CoPs in the academy? This article
      addresses these questions and provides guidance for those in search of community.

PMID- 23969472
TI  - Iatrogenic venous thrombosis secondary to supplemental medicine toxicity.
AB  - OBJECTIVE: We described a case of cerebral venous sinus thrombosis in a patient
      taking multiple supplements as part of a naturopathic anti-aging regimen.
      METHODS: Case report. RESULTS: The patient presented with a thalamic infarct
      associated with a thrombus in the vein of Galen. He reported no previous history
      of endocrinopathy and no known hypercoagulability risk factors. He was treated
      with therapeutic anticoagulation resulting in improvement. Diagnostic workup
      revealed hyperthyroidism and gonadotrophic deficiency attributed to significant
      supplement medicine usage. CONCLUSION: This case highlights a potential risk of
      dietary supplements. Use of these supplements may be a risk factor for idiopathic
      cerebral venous thrombosis.

PMID- 23969473
TI  - In vivo and in vitro estrogenic activity of extracts from Erythrina poeppigiana
      (Fabaceae).
AB  - In developing countries, around 80% of the population still resorts on
      traditional medicine for their primary health care. Erythrina poeppigiana (Walp.)
      O.F. Cook, one of these medicinal plants, was found to be particularly rich in
      isoflavonoids which exhibited, individually, significant estrogenic activity in
      vitro. The possible combined effects of these bioactive isoflavones, as they are
      naturally found in the crude extracts of E. poeppigiana, prompted us to assess
      their in vivo estrogenicity. We first tested the ability of the extracts to
      transactivate estrogen receptor alpha (ERalpha) in vitro using U2OS human
      osteosarcoma cells. We next investigated their effects in vivo in an uterotrophic
      assay, using ovariectomized rats treated with the extracts at the doses of 50,
      100, 200, and 400 mg/kg BW/d orally for 3 days. Finally, we assessed their
      ability to relieve hot flushes, using data loggers. At the end of treatments,
      animals were sacrificed, and organs (mammary glands, vagina, and uteri) were
      collected for histo-morphometric analyses. The methanol extract significantly and
      dose-dependently transactivated ERalpha at all tested doses. All extracts induced
      significant increases of vaginal and uterine epithelial heights. Only the
      dichloromethane extract could significantly relieve hot flushes as estradiol.
      These results indicate that E. poeppigiana extracts have estrogen-like effects in
      vivo, suggesting that its active principles act in synergy when they are taken in
      combination in the crude extract. These findings, therefore, support the
      traditional use of E. poeppigiana to alleviate some menopausal problems; our
      previous phytochemical investigations contribute to the standardization of this
      phytomedicine.

PMID- 23969474
TI  - Choroid Metastasis from Testicular Carcinoma: A Rare Entity.
AB  - The aim of this report is to contribute to the clinical understanding of choroid
      metastasis from testicular carcinoma. A young male patient presented with loss of
      vision in his left eye with ptosis and proptosis. Fundoscopy revealed bullous
      retinal detachment with dark hazy vitreous. The preliminary diagnosis of choroid
      carcinoma with vitreous involvement was made by an ophthalmologist. Later in the
      physical examination, there was a firm painless left testicular swelling.
      Testicular tumor markers were raised. Based on ultrasonography, MRI and PET-CT, a
      clinical diagnosis of left testicular carcinoma metastasizing to the left choroid
      and vitreous was made. A mixed germ cell tumor was reported on histopathological
      examination. After cisplatin-based chemotherapy, serum tumor markers normalized
      and vision improved. Exceptional choroidal and vitreous metastases with absence
      of other visceral and bony involvement constituted the presenting sign. Although
      rare, testicular carcinoma must be considered to metastasize to the eye,
      especially if loss of vision is the chief complaint. 

PMID- 23969475
TI  - Comparison of the Agency for Healthcare Research and Quality Patient Safety
      Indicator Rates Among Veteran Dual Users.
AB  - This study compares rates of 11 Agency for Healthcare Research and Quality
      Patient Safety Indicators (PSIs) among 266 203 veteran dual users (ie, those with
      hospitalizations in both the Veterans Health Administration [VA] and the private
      sector through Medicare fee-for-service coverage) during 2002 to 2007. PSI risk
      adjusted rates were calculated using the PSI software (version 3.1a). Rates of
      pressure ulcer, central venous catheter-related bloodstream infections, and
      postoperative sepsis, areas in which the VA has focused quality improvement
      efforts, were found to be significantly lower in the VA than in the private
      sector. VA had significantly higher rates for 7 of the remaining 8 PSIs, although
      the rates of only 2 PSIs (postoperative hemorrhage/hematoma and accidental
      puncture or laceration) remained higher in the VA after sensitivity analyses were
      conducted. A better understanding of system-level differences in coding practices
      and patient severity, poorly documented in administrative data, is needed before
      conclusions about differences in quality can be drawn. 

PMID- 23969476
TI  - Prognosis of the bradycardia pacemaker recipient assessed at first implantation:
      a nationwide cohort study.
AB  - OBJECTIVE: Pacing technology and care have improved notably over the past decade,
      justifying an update on the long-term prognosis and pre-implantation determinants
      of prognosis of bradycardia pacemaker (PM) recipients. DESIGN: Prospective cohort
      study. SETTING: 23 Dutch pacemaker centres PATIENTS: Pre-implantation
      characteristics of 1517 patients receiving a first bradycardia PM between 2003
      2007 were studied in relation to survival. INTERVENTIONS: None; patients were
      followed up during routine clinical practice. MAIN OUTCOME MEASURES: Cause and
      time to death. RESULTS: At the end of a mean follow-up of 5.8 (SD 1.1) years, 512
      patients (33%) died, mostly of non-cardiac cause (67%). There were two PM related
      deaths. Survival rates were 93%, 81%, 69%, and 61% after 1, 3, 5 and 7 years,
      respectively. PM recipients without concomitant cardiovascular disease at
      implantation showed survival rates comparable to age and sex matched controls.
      Predictors at time of implantation associated with cardiac mortality were: age,
      coronary artery disease (CAD), diabetes, heart failure, valve disease, and the
      indication for PM implantation. Predictors for all cause mortality were: male
      gender, age, body mass index, CAD, cardiac surgery, diabetes, heart failure, and
      maintained atrioventricular synchrony. CONCLUSIONS: A pre-implantation history of
      heart failure, CAD, and diabetes are the most important predictors for worse
      prognosis in PM recipients. Without baseline heart disease, survival rates equal
      that of the general population, suggesting that the prognosis of contemporary PM
      recipients is mainly determined by comorbid diseases and a bradycardia pacing
      indication as such does not influence survival. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT00135174.

PMID- 23969477
TI  - Bile acids induce arrhythmias: old metabolite, new tricks.

PMID- 23969478
TI  - Indexing aortic valve area by body surface area increases the prevalence of
      severe aortic stenosis.
AB  - BACKGROUND: To account for differences in body size in patients with aortic
      stenosis, aortic valve area (AVA) is divided by body surface area (BSA) to
      calculate indexed AVA (AVAindex). Cut-off values for severe stenosis are <1.0 cm2
      for AVA and <0.6 cm2/m2 for AVAindex. OBJECTIVE: To investigate the influence of
      indexation on the prevalence of severe aortic stenosis and on the predictive
      accuracy regarding clinical outcome. METHODS: Echocardiographic and
      anthropometric data from a retrospective cohort of 2843 patients with aortic
      stenosis (jet velocity >2.5 m/s) and from 1525 patients prospectively followed in
      the simvastatin and ezetimibe in aortic stenosis (SEAS) trial were analysed.
      RESULTS: The prevalence of severe stenosis increased with the AVAindex criterion
      compared to AVA from 71% to 80% in the retrospective cohort, and from 29% to 44%
      in SEAS (both p<0.001). Overall, the predictive accuracy for aortic valve events
      was virtually identical for AVA and AVAindex in the SEAS population (mean follow
      up of 46 months; area under the receiver operating characteristic curve: 0.67
      (95% CI 0.64 to 0.70) vs. 0.68 (CI 0.65 to 0.71) (NS). However, 213 patients
      additionally categorised as severe by AVAindex experienced significantly less
      valve related events than those fulfilling only the AVA criterion (p<0.001).
      CONCLUSIONS: Indexing AVA by BSA (AVAindex) significantly increases the
      prevalence of patients with criteria for severe stenosis by including patients
      with a milder degree of the disease without improving the predictive accuracy for
      aortic valve related events.

PMID- 23969480
TI  - DNA damage response-related proteins in gastric cancer: ATM, Chk2 and p53
      expression and their prognostic value.
AB  - OBJECTIVES: The aims of this study were to assess expressions of the DNA damage
      response (DDR)-related proteins and to investigate their clinical significances
      in gastric carcinoma. METHODS: Two independent cohorts, a training set (n=524)
      and validation set (n=394), of gastric cancer patients were enrolled. Ataxia
      telangiectasia mutated (ATM), checkpoint kinase 2 (Chk2), and p53 expressions
      were examined by immunohistochemistry using tissue microarray. RESULTS: ATM loss,
      Chk2 loss, and p53 positivity were observed in 21.8, 14.1, and 36.1% of the
      training set, and in 17.3, 12.2, and 35.8% of the validation set, respectively.
      In the training set, the aberrant expressions of ATM, Chk2, or p53 were
      significantly associated with an advanced TNM stage and poor disease-specific
      survival. This association was verified in the validation set. Chk2 positivity
      and p53 negativity were significantly related to a prolonged disease-specific
      survival. Also, patients with nonaberrant expressional levels of all 3 DDR
      related proteins had a more favorable outcome than others. Multivariate analyses
      showed that Chk2 loss and at least 1 aberrant DDR-related protein remained as
      independent prognostic factors of poor disease-specific survival. CONCLUSIONS:
      This study elucidated the prognostic implications of DDR-related proteins, and
      suggests that their aberrant expressions play critical roles in the development
      and progression of gastric cancer.

PMID- 23969481
TI  - Pre-school hyperactivity/attention problems and educational outcomes in
      adolescence: prospective longitudinal study.
AB  - BACKGROUND: High levels of attentional and hyperactivity problems in school-aged
      children, even if subthreshold for attention-deficit hyperactivity disorder
      (ADHD), are associated with academic under-achievement. Few large-scale,
      community-based studies have investigated the relationship between pre-school and
      adolescence. AIMS: To investigate whether pre-school hyperactivity/inattention
      and conduct problems are independently associated with academic outcomes at age
      16. METHOD: Data from the prospective, population-based Avon Longitudinal Study
      of Parents and Children (ALSPAC) were used. After adjusting for a broad range of
      confounder variables, the associations between parent-rated
      hyperactivity/inattention and conduct problems measured at age 3 and academic
      outcomes at age 16 (national General Certificate of Secondary Education (GCSE)
      examination results) were investigated (n = 11 640). RESULTS: Both early
      hyperactivity/inattention and conduct problems had negative effects on academic
      outcomes. In adjusted analyses, abnormal hyperactivity/inattention scores were
      associated with reductions of ten GCSE points in boys. Borderline and abnormal
      conduct problem scores were associated with reductions of 9-10 and 12-15 points
      respectively. CONCLUSIONS: Pre-school hyperactivity/inattention and conduct
      problems carry risk of worse academic outcomes at 16.

PMID- 23969482
TI  - Decision-making capacity for treatment in psychiatric and medical in-patients:
      cross-sectional, comparative study.
AB  - BACKGROUND: Is the nature of decision-making capacity (DMC) for treatment
      significantly different in medical and psychiatric patients? AIMS: To compare the
      abilities relevant to DMC for treatment in medical and psychiatric patients who
      are able to communicate a treatment choice. METHOD: A secondary analysis of two
      cross-sectional studies of consecutive admissions: 125 to a psychiatric hospital
      and 164 to a medical hospital. The MacArthur Competence Assessment Tool -
      Treatment and a clinical interview were used to assess decision-making abilities
      (understanding, appreciating and reasoning) and judgements of DMC. We limited
      analysis to patients able to express a choice about treatment and stratified the
      analysis by low and high understanding ability. RESULTS: Most people scoring low
      on understanding were judged to lack DMC and there was no difference by hospital
      (P = 0.14). In both hospitals there were patients who were able to understand yet
      lacked DMC (39% psychiatric v. 13% medical in-patients, P<0.001). Appreciation
      was a better 'test' of DMC in the psychiatric hospital (where psychotic and
      severe affective disorders predominated) (P<0.001), whereas reasoning was a
      better test of DMC in the medical hospital (where cognitive impairment was
      common) (P = 0.02). CONCLUSIONS: Among those with good understanding, the
      appreciation ability had more salience to DMC for treatment in a psychiatric
      setting and the reasoning ability had more salience in a medical setting.

PMID- 23969483
TI  - Treatment of child anxiety disorders via guided parent-delivered cognitive
      behavioural therapy: randomised controlled trial.
AB  - BACKGROUND: Promising evidence has emerged of clinical gains using guided self
      help cognitive-behavioural therapy (CBT) for child anxiety and by involving
      parents in treatment; however, the efficacy of guided parent-delivered CBT has
      not been systematically evaluated in UK primary and secondary settings. AIMS: To
      evaluate the efficacy of low-intensity guided parent-delivered CBT treatments for
      children with anxiety disorders. METHOD: A total of 194 children presenting with
      a current anxiety disorder, whose primary carer did not meet criteria for a
      current anxiety disorder, were randomly allocated to full guided parent-delivered
      CBT (four face-to-face and four telephone sessions) or brief guided parent
      delivered CBT (two face-to-face and two telephone sessions), or a wait-list
      control group (trial registration: ISRCTN92977593). Presence and severity of
      child primary anxiety disorder (Anxiety Disorders Interview Schedule for DSM-IV,
      child/parent versions), improvement in child presentation of anxiety (Clinical
      Global Impression - Improvement scale), and change in child anxiety symptoms
      (Spence Children's Anxiety Scale, child/parent version and Child Anxiety Impact
      scale, parent version) were assessed at post-treatment and for those in the two
      active treatment groups, 6 months post-treatment. RESULTS: Full guided parent
      delivered CBT produced superior diagnostic outcomes compared with wait-list at
      post-treatment, whereas brief guided parent-delivered CBT did not: at post
      treatment, 25 (50%) of those in the full guided CBT group had recovered from
      their primary diagnosis, compared with 16 (25%) of those on the wait-list
      (relative risk (RR) 1.85, 95% CI 1.14-2.99); and in the brief guided CBT group,
      18 participants (39%) had recovered from their primary diagnosis post-treatment
      (RR = 1.56, 95% CI 0.89-2.74). Level of therapist training and experience was
      unrelated to child outcome. CONCLUSIONS: Full guided parent-delivered CBT is an
      effective and inexpensive first-line treatment for child anxiety.

PMID- 23969484
TI  - Pattern recognition analysis of anterior cingulate cortex blood flow to classify
      depression polarity.
AB  - Differentiating bipolar from recurrent unipolar depression is a major clinical
      challenge. In 18 healthy females and 36 females in a depressive episode--18 with
      bipolar disorder type I, 18 with recurrent unipolar depression--we applied
      pattern recognition analysis using subdivisions of anterior cingulate cortex
      (ACC) blood flow at rest, measured with arterial spin labelling. Subgenual ACC
      blood flow classified unipolar v. bipolar depression with 81% accuracy (83%
      sensitivity, 78% specificity).

PMID- 23969485
TI  - Mental disorders and risk of accidental death.
AB  - BACKGROUND: Little is known about accidental death risks among psychiatric
      patients. AIMS: To examine this issue in the most comprehensive study to date.
      METHOD: National cohort study of all Swedish adults (n = 6 908 922) in 2001-2008.
      RESULTS: There were 22 419 (0.3%) accidental deaths in the total population,
      including 5933 (0.9%) accidental deaths v. 3731 (0.6%) suicides among psychiatric
      patients (n = 649 051). Of persons who died from accidents, 26.0% had any
      psychiatric diagnosis v. 9.4% in the general population. Accidental death risk
      was four- to sevenfold among personality disorders, six- to sevenfold among
      dementia, and two- to fourfold among schizophrenia, bipolar disorder, depression
      or anxiety disorders, and was not fully explained by comorbid substance use.
      Strong associations were found irrespective of sociodemographic characteristics,
      and for different types of accidental death (especially poisoning or falls).
      CONCLUSIONS: All mental disorders were strong independent risk factors for
      accidental death, which was substantially more common than suicide.

PMID- 23969486
TI  - The neurology of aretaeus: radix pedis neurologia.
AB  - Aretaeus (Aretaios) was a physician born in Cappadocia in about the 2nd century
      AD, a student of medicine and physician in Alexandria. His works are found in
      eight books which espoused the physiological and pathological views of the
      Hippocratic principles derived from the pneumatists and the eclectic schools.
      Though he has been called the forgotten physician, it has been said that: 'after
      Hippocrates no single Greek author has equalled Aretaios'. In order to give an
      indication of his neurological legacy, this paper offers a summary of and
      quotations from his principal neurological contributions: migraine, vertigo,
      tetanus, epilepsy, melancholia, strokes and paralysis. One of his most important
      discoveries was the notion that the pyramidal tract decussates. 

PMID- 23969487
TI  - Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle
      arrest and apoptosis.
AB  - In the present study, we investigated the effect of apigenin, a flavonoid widely
      present in fruits and vegetables, on a tongue oral cancer-derived cell line (SCC
      25) and on a keratinocyte cell line (HaCaT), with the aim of unveiling its
      antiproliferative mechanisms. The effect of apigenin on cell growth was evaluated
      by MTT assay, while apoptosis was investigated by phosphatidyl serine membrane
      translocation and cell cycle distribution by propidium iodide DNA staining
      through flow cytometry. In addition the expression of cyclins and cyclin
      dependent kinases was evaluated by western blotting. A reduction of apigenin
      induced cell growth was found in both cell lines, although SCC-25 cells were
      significantly more sensitive than the immortalized keratinocytes, HaCaT.
      Moreover, apigenin induced apoptosis and modulated the cell cycle in SCC-25
      cells. Apigenin treatment resulted in cell cycle arrest at both G0/G1 and G2/M
      checkpoints, while western blot analysis revealed the decreased expression of
      cyclin D1 and E, and inactivation of CDK1 upon apigenin treatment. These results
      demonstrate the anticancer potential of apigenin in an oral squamous cell
      carcinoma cell line, suggesting that it may be a very promising chemopreventive
      agent due to its cancer cell cytotoxic activity and its ability to act as a cell
      cycle modulating agent at multiple levels.

PMID- 23969488
TI  - Regional and socioeconomic disparities in the treatment of unruptured cerebral
      aneurysms in the USA: 2000-2010.
AB  - BACKGROUND: The Institute of Medicine called attention to the pervasive
      differences in treatments and outcomes between ethnic groups. We sought to
      highlight the geographic and racial disparities in access to treatment for
      unruptured cerebral aneurysms. METHODS: We performed a retrospective cohort study
      involving patients with unruptured cerebral aneurysms from 2000 to 2010,
      registered in the National Inpatient Sample (NIS) database. Primary outcomes were
      those patients receiving treatment and the ratio of untreated to treated
      aneurysms per state. The purpose of this study was to determine if there were
      geographic and racial disparities in access to treatment of unruptured cerebral
      aneurysms based on the NIS. Logistic regression and analysis of variance (ANOVA)
      techniques were used. RESULTS: There were 57 418 patients diagnosed with
      unruptured aneurysms (mean age 61.4 years, 70.5% females), with 18 231 undergoing
      treatment. Males (OR 0.67, 95% CI 0.64 to 0.71, p<0.0001), Asian (OR 0.88, 95% CI
      0.81 to 0.96, p=0.003), Hispanic (OR 0.76, 95% CI 0.65 to 0.90, p=0.001), African
      American (OR 0.57, 95% CI 0.53 to 0.62, p<0.0001), and patients without insurance
      (OR 0.76, 95% CI 0.67 to 0.87, p<0.0001) were associated with decreased chance of
      treatment. The opposite was true for lower Charlson Comorbidity Index (OR 3.03,
      95% CI 2.71 to 3.39, p<0.0001), coverage by Medicaid (OR 1.12, 95% CI 1.03 to
      1.23, p=0.012), or private insurance (OR 1.92, 95% CI 1.80 to 2.04, p<0.0001),
      and lower income (OR 1.22, 95% CI 1.15 to 1.31, p<0.0001). Significant regional
      variability was observed among the different states (p=0.006, ANOVA), with
      Maryland being an outlier. CONCLUSIONS: Based on the NIS database, the rate of
      treatment of unruptured cerebral aneurysms varies according to sex, race, and
      region.

PMID- 23969489
TI  - Retrograde mechanico-chemical endovenous ablation of infrageniculate great
      saphenous vein for persistent venous stasis ulcers.
AB  - OBJECTIVE: To present the use of retrograde mechanico-chemical endovenous
      ablation for ablating the remaining below-knee great saphenous vein in patients
      with venous stasis ulcers persisting after above-knee great saphenous vein
      ablation. METHODS: This small study includes six patients with persistent
      C6EpAsPr ulcers following above-knee great saphenous vein ablation with no
      incompetent perforators. They were treated using retrograde mechanico-chemical
      endovenous ablation approach followed by Unna therapy, followed up on post op
      days 3 and 30 with ultrasound, and subsequent weekly visits until the wound
      healed. RESULTS: Six patients (four men and two women), have average ulcer size
      of 4.1 cm(2). There was no nerve injury or other complications after mechanico
      chemical endovenous ablation. These patients had an average of 28 +/- 11 days
      healing time, compared with a mean of five months in traditional method.
      CONCLUSION: Mechanico-chemical endovenous ablation can be safe and effective in
      the treatment of patients with below-knee great saphenous vein insufficiency with
      venous ulcers.

PMID- 23969490
TI  - Variations in ultrasound scanning protocols in the UK for suspected deep vein
      thrombosis in outpatients.
AB  - AIMS: To assess current ultrasound scanning protocol in outpatients with
      suspected deep vein thrombosis (DVT), in particular whether practitioners
      routinely scanned calf veins. METHODS: A standard questionnaire was sent out via
      post to all radiology departments in the United Kingdom (UK) and via the British
      Medical Ultrasound Society (BMUS) website in 2010. Responses were entered into
      Access(r) and database queries were run to analyse responses. Free-text comments
      were taken into account in our analysis. RESULTS: A total of 277 responses (50
      through the BMUS website) were received (46% postal response rate). Of them, six
      were excluded as these were incomplete. Thus, 97 (36%) were consultants, 13 (5%)
      accredited vascular scientists (AVSs), 153 (56%) sonographers and six (2%) higher
      radiology trainees. All AVSs scanned the whole limb and used all three modalities
      of compression, colour and pulse wave Dopplers. Practice across other health-care
      professionals varied. In all, 120/176 (68%) of other health-care professionals
      trained in vascular ultrasound scanned the whole limb routinely and 82/120 of
      these used all three scanning modalities. Trained sonographers scanned the whole
      limb significantly more than the medical cohort (P = 0.017). The use of all three
      modalities varied significantly between AVS and the non-AVS trained professionals
      (P = 0.0194), the trained medical cohort of consultants and sonographers (P =
      0.0001), and trained and non-trained respondents (P = 0.0113). The commonly
      chosen reason for not scanning the whole limb was that it had poor sensitivity
      for calf vein DVTs. Free-text reasons for not scanning the whole limb routinely
      included local protocols prohibiting it. CONCLUSIONS: There is a discrepancy
      between the scanning protocols of medically trained and allied health-care
      professionals, trained or otherwise in vascular ultrasound, and between these
      groups and AVSs. This is likely to have an impact on clinical governance.

PMID- 23969491
TI  - Water-soluble conjugated polyelectrolyte brush encapsulated rare-earth ion doped
      nanoparticles with dual-upconversion properties for multicolor cell imaging.
AB  - A concise route to prepare water-soluble rare-earth ion doped upconversion
      nanoparticles (UCNPs) by encapsulation of grafted cationic conjugated
      polyelectrolyte brushes (PFNBr) is reported. Integrating two kinds of
      upconversion materials effectively addresses multicolor fluorescence by
      introducing the concept of dual-upconversion. 

PMID- 23969492
TI  - Reply: To PMID 23548890.

PMID- 23969493
TI  - AKT activation and telomerase reverse transcriptase expression are concurrently
      associated with prognosis of gastric cancer.
AB  - AKT is a protein in the phosphatidylinositol-3 kinase (PI3K) pathway and
      associated with diverse pro-tumoral responses. Activation of the human telomere
      reverse transcriptase (hTERT) is one of AKT's tumorigenic effects. In this study,
      the significance of AKT phosphorylation and hTERT on prognosis of gastric cancer
      were examined. AKT activation by epidermal growth factor increased hTERT
      expression and telomerase activity. In contrast, AKT inactivation by inhibitors
      and knockdown decreased hTERT expression and telomerase activity in MKN28 gastric
      cancer cells. In 40 gastric cancer tissues, significant correlations were found
      among the levels of phosphorylated AKT (pAKT), hTERT expression, and telomer
      length. The pAKT levels or the levels of pAKT/hTERT were not associated with
      clinicopathological parameters, including stage and nodal metastasis. However,
      survival rates of the pAKT-high patients or the pAKT-high and hTERT-high patients
      were significantly poorer than those in other patients. These findings suggest
      that AKT and hTERT are good molecular targets for the treatment of gastric
      cancer. 

PMID- 23969495
TI  - Acute myocardial infarction caused by tumor-associated thrombotic
      thrombocytopenic purpura: case report.
AB  - OBJECTIVE: To describe a case with acute myocardial infarction caused by gastric
      carcinoma-associated thrombotic thrombocytopenic purpura. CLINICAL PRESENTATION
      AND INTERVENTION: A 79-year-old man was admitted with abdominal pain and pyrexia.
      He later developed cardiac complications and microangiopathy that indicated
      worsening progression. Manifold evidence confirmed the diagnosis of myocardial
      infarction caused by thrombotic thrombocytopenic purpura. The patient was treated
      mainly with plasma transfusion incorporated with steroids. CONCLUSION: This case
      should remind physicians to consider microangiopathy as a differential diagnosis
      in patients with unexplained cardiac symptoms or atypical presentation. Early
      diagnosis and treatment are helpful in decreasing the sequelae of this syndrome.

PMID- 23969496
TI  - Identification of optimal target gene regions for hepatitis B virus genotyping by
      DNA sequencing.
AB  - OBJECTIVES: DNA sequencing is the gold standard for hepatitis B virus (HBV)
      genotyping. We investigated the intergenotypic discriminatory capabilities of
      various target gene regions over the entire HBV genome, introducing a novel data
      evaluation approach generally applicable in viral genotyping. METHODS: Complete
      genome sequences of seventy HBV variants obtained from the sera of 50 Syrian
      patients were determined and assigned GenBank accession No. from JN257148 to
      JN257217. Nucleotide sequence contigs were analyzed together with the NCBI
      reference genome set of HBV genotypes. Nine target gene regions were analyzed by
      phylogenetic and scored BLAST analyses. Thirty-one overlapping 300-bp sequence
      segments over the entire genome were also analyzed using a scored BLAST analysis,
      and intergenotypic discriminatory capabilities were statistically estimated for
      each. RESULTS: Intergenotype discrimination was extremely significant when
      targeting either the complete genome, the entire coding sequence of either P or S
      genes, or any 300-bp sequence segment over the coding sequences of S protein or
      the polymerase N-terminal domain. Interestingly, intergenotypic discriminatory
      capability correlated negatively with intragenotype variation. CONCLUSIONS: The
      intragenotypic conservation of certain target gene regions determines the
      intergenotypic discriminatory capability and allows reliable genotyping with
      relatively short segments. Our referential genome-wide tabulated guide allows for
      selecting candidate target gene regions for sequencing-based HBV genotyping. (c)
      2013 S. Karger AG, Basel.

PMID- 23969497
TI  - Ethylbenzene-induced hearing loss, neurobehavioral function, and neurotransmitter
      alterations in petrochemical workers.
AB  - OBJECTIVE: To estimate hearing loss, neurobehavioral function, and
      neurotransmitter alteration induced by ethylbenzene in petrochemical workers.
      METHODS: From two petrochemical plants, 246 and 307 workers exposed to both
      ethylbenzene and noise were recruited-290 workers exposed to noise only from a
      power station plant and 327 office personnel as control group, respectively.
      Hearing and neurobehavioral functions were evaluated. Serum neurotransmitters
      were also determined. RESULTS: The prevalence of hearing loss was much higher in
      petrochemical groups than that in power station and control groups (P < 0.05).
      Compared with the control group, scores of neurobehavioral function reflecting
      learning and memory were decreased in petrochemical workers (P < 0.05), as well
      as acetylcholinesterase activity. Negative correlation was shown between
      neurobehavioral function and acetylcholinesterase. CONCLUSIONS: Ethylbenzene
      exposure might be associated with hearing loss, neurobehavioral function
      impairment, and imbalance of neurotransmitters.

PMID- 23969498
TI  - State-level estimates of cancer-related absenteeism costs.
AB  - BACKGROUND: Cancer is one of the top five most costly diseases in the United
      States and leads to substantial work loss. Nevertheless, limited state-level
      estimates of cancer absenteeism costs have been published. METHODS: In analyses
      of data from the 2004-2008 Medical Expenditure Panel Survey, the 2004 National
      Nursing Home Survey, the U.S. Census Bureau for 2008, and the 2009 Current
      Population Survey, we used regression modeling to estimate annual state-level
      absenteeism costs attributable to cancer from 2004 to 2008. RESULTS: We estimated
      that the state-level median number of days of absenteeism per year among employed
      cancer patients was 6.1 days and that annual state-level cancer absenteeism costs
      ranged from $14.9 million to $915.9 million (median = $115.9 million) across
      states in 2010 dollars. Absenteeism costs are approximately 6.5% of the costs of
      premature cancer mortality. CONCLUSIONS: The results from this study suggest that
      lost productivity attributable to cancer is a substantial cost to employees and
      employers and contributes to estimates of the overall impact of cancer in a state
      population.

PMID- 23969499
TI  - Chronic obstructive pulmonary disease prevalence among nonsmokers by occupation
      in the United States.
AB  - OBJECTIVE: To examine the prevalence of chronic obstructive pulmonary disease
      (COPD) among nonsmokers by occupation in the United States. METHODS: The 1997 to
      2004 National Health Interview Survey data for working adults aged 25 years or
      more were used to estimate the COPD prevalence and to examine change in COPD
      prevalence between 1997 to 2000 and 2001 to 2004 by occupational groups. RESULTS:
      During 1997 to 2004, COPD prevalence was 2.8%. The COPD prevalence was highest in
      financial records processing (4.6%) occupations. There was a slight increase in
      COPD prevalence during the two survey periods from 2.8% during 1997 to 2000
      compared with 2.9% during 2001 to 2004. CONCLUSIONS: No significant changes in
      the COPD prevalence between the two periods were found. Nevertheless, the
      elevated COPD prevalence in certain occupational groups suggests that other risk
      factors play a role in developing COPD.

PMID- 23969501
TI  - Hits and misses: screening commercial drivers for obstructive sleep apnea using
      guidelines recommended by a joint task force.
AB  - OBJECTIVE: To evaluate joint task force criteria-based screening for severe
      obstructive sleep apnea (s-OSA) in commercial drivers. METHODS: Among a community
      based cohort of licensed commercial vehicle drivers, we assessed utility of the
      joint task force criteria. We conducted full, 14-channel overnight
      polysomnography in all drivers, defining s-OSA as an apnea-hypopnea index of 30
      or more per hour. RESULTS: One hundred of 104 drivers with successful
      polysomnography studies were predominantly obese (median body mass index = 32.8
      kg/m; interquartile range = 26.8 to 37.4) and had a median apnea-hypopnea index
      of 20.6 per hour (interquartile range = 10.0 to 34.2). Examination-based criteria
      were more effective (sensitivity = 80%; negative posttest probability [nPTP] =
      17%) than symptom-based criteria (sensitivity = 63%; nPTP = 23%). Examination and
      symptom-based criteria combined had high sensitivity (97%) and low nPTP (7%), but
      poor specificity (19%). CONCLUSIONS: Examination-based criteria missed 20% of s
      OSA cases. Combining examination with confidentially reported symptoms improved
      sensitivity but required confirmatory polysomnography in 86%, supporting
      universal screening of all drivers.

PMID- 23969500
TI  - Threshold value estimation for respirable quartz dust exposure and silicosis
      incidence among workers in the german porcelain industry.
AB  - OBJECTIVES: To estimate a threshold value for the respirable quartz dust
      concentration and silicosis incidence (1/1, ILO 1980/2000) in the German
      porcelain worker cohort. METHODS: Forty incident cases occurred among 17,144
      workers. Estimation of the relationship to cumulative respirable quartz dust
      exposures by using Cox regression with restricted cubic splines (7 knots or less)
      and fractional polynomials (degrees 5 or less). Threshold estimates were obtained
      by subtracting candidate values from the time-dependent concentration data
      (setting the result to zero if negative) and recalculating cumulative exposure.
      RESULTS: Best threshold estimate was 0.25 mg/m (95% confidence interval: 0.15 to
      0.30 mg/m). CONCLUSIONS: A concentration threshold for silicosis risk is
      plausible. A threshold Cox model fitted the data significantly better than a
      nonthreshold model, summarized the cohort information without a loss in extracted
      information and more simply than restricted cubic splines and fractional
      polynomials.

PMID- 23969502
TI  - An industry-based cohort study of the association between weight gain and
      hypertension risk among rotating shift workers.
AB  - OBJECTIVES: We investigated whether the association between shift work and
      hypertension is independent of weight gain. METHODS: Subjects were 10,173 male
      employees (9209 daytime workers, 964 three-shift workers; mean follow-up period:
      12.7 years). Hypertension was defined as systolic blood pressure 140 mm Hg or
      more or diastolic blood pressure 90 mm Hg or more. The risk of developing
      hypertension among shift workers was estimated using a Cox proportional hazards
      model with adjustment for several factors. RESULTS: Analysis revealed that "shift
      work" (hazard ratio [HR]: 1.85; 95% confidence interval [CI]: 1.68, 2.03),
      "baseline body mass index" (HR: 1.13; 95% CI: 1.12, 1.15), and "increase in body
      mass index during follow-up" (HR: 1.15; 95% CI: 1.13, 1.17) were significant
      independent risk factors for hypertension. CONCLUSIONS: Shift work is a
      significant risk factor for hypertension that is independent of both starting
      weight and weight gained over years of work.

PMID- 23969503
TI  - Maternal occupation and term low birth weight in a predominantly latina
      population in los angeles, california.
AB  - OBJECTIVES: Focusing on Latinas, we investigated whether maternal occupations
      during pregnancy increase term low birth weight (TLBW) (less than 2500 g; 37
      weeks or more). METHODS: In a case-control study (n = 1498) nested within a 2003
      birth cohort (n = 58,316) in Los Angeles County, California (65% Latina), we
      assessed the influence of maternal occupation on TLBW, using Occupational Codes
      based on the 2000 US Census Occupational Classification System. RESULTS: Odds
      ratios (ORs) for TLBW were increased among women working during pregnancy in
      "transportation and material moving operations" (adjusted OR = 3.28; 95%
      confidence interval = 1.00 to 10.73), "food preparation and serving occupations"
      (adjusted OR = 3.03, 95% confidence interval = 1.21 to 7.62), or "production
      occupations" (adjusted OR = 2.63, 95% confidence interval = 1.01 to 6.82)
      compared with "office occupations;" 73% to 93% of women working in these higher
      risk jobs were immigrant Latinas. CONCLUSIONS: Working conditions in various jobs
      held mainly by first-generation immigrant Latinas increase risks for TLBW and
      need to be addressed to develop strategies to reduce TLBW.

PMID- 23969505
TI  - Occupation and head and neck cancer risk in men: results from the ICARE study, a
      French population-based case-control study.
AB  - OBJECTIVE: To investigate the associations between occupations and head and neck
      (HN) cancer risk in men. METHODS: ICARE is a French population-based case-control
      study on HN cancer. Analyses included 1833 cases and 2747 controls. Complete
      occupational history was collected. Odds ratios (ORs) were estimated for
      occupations and industries ever held and according to duration of employment.
      RESULTS: Elevated ORs, increasing with duration of employment, were observed for
      several occupations, including cleaners (OR = 1.7; 95% confidence interval [CI],
      1.0 to 2.8), launderers (OR = 6.8; CI, 1.3 to 34.4), firefighters (OR = 3.9; CI,
      1.4 to 11.2), several agricultural occupations, welders (OR = 1.9; CI, 1.3 to
      2.8), structural metal preparers and erectors (OR = 2.1; CI, 1.2 to 3.7), rubber
      workers (OR = 2.0; CI, 1.0 to 3.9), several construction occupations, and
      material-handling equipment operators (OR = 1.8; CI, 1.1 to 2.9). Analyses by
      industry corroborated these findings. CONCLUSIONS: These results confirmed the
      role of occupational exposures in HN cancer.

PMID- 23969504
TI  - Long-term socioprofessional and psychological status in workers investigated for
      occupational asthma in quebec.
AB  - OBJECTIVE: To compare the long-term status of workers with occupational asthma
      (OA) with those of subjects with work-exacerbated asthma (WEA) and nonasthmatic
      (NA) workers. METHODS: We contacted 179 subjects investigated for suspected OA at
      Hopital du Sacre-Coeur de Montreal, Montreal, Quebec, Canada, from 1997 to 2007.
      Participants completed questionnaires on psychological and functional status,
      followed by a telephone interview about socioprofessional outcomes and health
      care utilization. RESULTS: The OA workers are more likely to have been removed
      from the workplace than the WEA workers. The health-related quality of life of
      all workers was still impaired. A high prevalence of psychiatric disorders was
      found among OA and WEA workers. Compared with WEA and OA workers, the NA group
      showed a higher rate of physician consultations for all causes. CONCLUSIONS:
      Regardless of the diagnosis they received, these workers need to benefit from
      psychosocial support in the period after investigation for suspicion of OA.

PMID- 23969506
TI  - Concordance between current job and usual job in occupational and industry
      groupings: assessment of the 2010 national health interview survey.
AB  - OBJECTIVE: To determine whether current job is a reasonable surrogate for usual
      job. METHODS: Data from the 2010 National Health Interview Survey were utilized
      to determine concordance between current and usual jobs for workers employed
      within the past year. Concordance was quantitated by kappa values for both simple
      and detailed industry and occupational groups. Good agreement is considered to be
      present when kappa values exceed 60. RESULTS: Overall kappa values +/- standard
      errors were 74.5 +/- 0.5 for simple industry, 72.4 +/- 0.5 for detailed industry,
      76.3 +/- 0.4 for simple occupation, 73.7 +/- 0.5 for detailed occupation, and
      80.4 +/- 0.6 for very broad occupational class. Sixty-five of 73 detailed
      industry groups and 78 of 81 detailed occupation groups evaluated had good
      agreement between current and usual jobs. CONCLUSIONS: Current job can often
      serve as a reliable surrogate for usual job in epidemiologic studies.

PMID- 23969508
TI  - Economic evaluation of an occupational health care guideline for prevention of
      weight gain among employees.
AB  - OBJECTIVE: To determine the cost-effectiveness and the financial return of a
      guideline for occupational physicians (OPs), aimed at the prevention of weight
      gain among employees. METHODS: The guideline consisted of a company-environment
      scan and up to five individual sessions with an OP. Sixteen OPs randomized to the
      guideline (n = 7) or usual care group (n = 9) recruited 275 and 249 employees.
      Costs were collected by using 3-monthly retrospective questionnaires. Quality
      adjusted life-years gained were determined with 6-monthly administered EuroQol
      5D. Waist circumference and body weight were measured at baseline and 18 months.
      RESULTS: Unfavorable differences were found on waist circumference (+1.6 cm; 95%
      confidence interval [CI], 0.27 to 2.90) and weight (+1.1 kg; 95% CI, 0.01 to
      2.15). Probabilities of cost-effectiveness were consistently less than 55%. Net
      employer loss was &OV0556;-158 (95% CI, -2865 to 2672). CONCLUSIONS: The
      occupational health care guideline was not cost-effective and no financial return
      was shown.

PMID- 23969509
TI  - Reactive airways dysfunction syndrome and considerations of irritant-induced
      Asthma.
AB  - The Occupational Medicine Forum is prepared by the ACOEM Occupational and
      Environmental Medical Practice Committee and does not necessarily represent an
      official ACOEM position. The Forum is intended for health professionals and is
      not intended to provide medical or legal advice, including illness prevention,
      diagnosis or treatment, or regulatory compliance. Such advice should be obtained
      directly from a physician and/or attorney. 

PMID- 23969507
TI  - Work-related knee injuries treated in US emergency departments.
AB  - OBJECTIVE: To characterize work-related knee injuries treated in US emergency
      departments (EDs). METHODS: We characterized work-related knee injuries treated
      in EDs in 2007 and examined trends from 1998 to 2007 by using the National
      Electronic Injury Surveillance System-occupational supplement. RESULTS: In 2007,
      184,300 (+/- 54,000; 95% confidence interval) occupational knee injuries were
      treated in US EDs, accounting for 5% of the 3.4 (+/- 0.9) million ED-treated
      occupational injuries. The ED-treated knee injury rate was 13 (+/- 4) injuries
      per 10,000 full-time equivalent workers. Younger workers and older female workers
      had high rates. Strains/sprains and contusions/abrasions were common-frequently
      resulting from falls and bodily reaction/overexertion events. Knee injury rates
      declined from 1998 through 2007. CONCLUSIONS: Knee injury prevention should
      emphasize reducing falls and bodily reaction/overexertion events, particularly
      among all youth and older women.

PMID- 23969510
TI  - Control of the spatial arrangements of supramolecular networks based on saddle
      distorted porphyrins by intermolecular hydrogen bonding.
AB  - Supramolecular integration of a saddle-distorted zinc(II) porphyrin complex,
      which has hydroxyl groups at the para-position of the four meso-aryl groups, has
      been demonstrated on the basis of hydrogen bonding among the peripheral hydroxyl
      groups. The hydrogen-bonding patterns were controlled by the recrystallization
      solvents and additives, and particularly, addition of a bifunctional ligand such
      as 4,4'-bipyridine (bpy). The coordination of bpy to form dinuclear Zn(II)
      porphyrin complexes causes a conformational difference: the dimeric complex with
      four hydroxyl groups is in an eclipsed form, however, a derivative without
      hydroxyl groups is in a staggered form due to the presence or absence of the
      intermolecular hydrogen bonding. In addition, the dimerization by the bpy
      coordination resulted in the expansion of the intermolecular space formed in the
      porphyrin networks, suggesting the potential to be applied for inclusion of guest
      molecules.

PMID- 23969511
TI  - Assessment of the peripheral ventilatory response to CO2 in heart failure
      patients: reliability of the single-breath test.
AB  - The assessment of chemoreflex sensitivity in heart failure patients is gaining
      increasing interest since recent studies demonstrated that augmented
      chemosensitivity is an independent predictor of mortality and represents an
      important pathogenic factor in the development of Cheyne-Stokes respiration. The
      single-breath CO2 test is a well-established method to quantify peripheral
      hypercapnic chemoreflex sensitivity. As the original criteria for the computation
      of the chemoreflex sensitivity in healthy subjects need to be modified in heart
      failure patients to take into account impaired cardiac function, the effects of
      such modifications on measurement reliability deserve investigation. Hence, we
      devised this study to assess the reliability of the single-breath CO2 test in
      heart failure patients. In 27 clinically stable, mild-to-moderate heart failure
      patients (age (mean+/-SD): 64+/-10 years, left ventricular ejection fraction:
      34+/-7%, NYHA class: 2.7+/-0.4), the test was administered on two consecutive
      days in the same conditions. Reliability was assessed by the standard error of
      measurement (SEM) and by the intraclass correlation coefficient (ICC). The mean
      value of the chemoreflex sensitivity on the two days was: 0.25 +/- 0.12 and 0.24
      +/- 0.12 l min(-1) mmHg(-1) (p = 0.45), respectively. The SEM was 0.05 l min(-1)
      mmHg(-1), indicating large intra-subject variability. Consequently, in order to
      be 95% confident that a real change has occurred between two measurements taken
      on the same individual (test-retest), the observed difference must be higher than
      +/-0.15 l min(-1) mmHg(-1), which is about 60% of the mean value across our
      population. The ICC was 0.71, indicating thatintra-subject variability, although
      high, is a limited (29%) portion of inter-subject variability. Intra-subject
      variability should be carefully taken into account when using the single-breath
      CO2 test in assessing changes in individual patients. The observed ICC indicates
      that this test may provide useful information for diagnostic/classification
      purposes. 

PMID- 23969512
TI  - Scalable alignment of three-dimensional cellular constructs in a microfluidic
      chip.
AB  - There have been considerable efforts to engineer three-dimensional (3D)
      microfluidic environments to enhance cellular function over conventional two
      dimensional (2D) cultures in microfluidic chips, but few involve topographical
      features, such as micro/nano-grooves, which are beneficial for cell types of
      cardiac, skeletal and neuronal lineages. Here we have developed a cost-effective
      and scalable method to incorporate micro-topographical cues into microfluidic
      chips to induce cell alignment. Using commercially available optical media as
      molds for replica molding, we produced large surface areas of
      polydimethylsiloxane (PDMS) micro-grooved substrates and plasma-bonded them to
      multiple microfluidic chips. Besides aligning a 2D monolayer of cells, the micro
      grooved substrate can align 3D cellular constructs on chip. C2C12 mouse myoblasts
      were cultured three-dimensionally in a microfluidic chip with incorporated PDMS
      micro-grooved substrate remodeled into an aligned 3D cellular construct, where
      the actin cytoskeleton and nuclei were preferentially oriented along the micro
      grooves. Cells within the 3D cellular constructs can align without being in
      direct contact with the micro-grooves due to synergism between topography and
      fluid shear stress. Aligned C2C12 3D cellular constructs showed enhanced
      differentiation into skeletal muscles as compared to randomly aligned ones. This
      novel method enables the routine inclusion of micro-topographical cues into 2D or
      3D microfluidic cultures to generate relevant physiological models for studying
      tissue morphogenesis and drug screening applications. 

PMID- 23969513
TI  - Absence of pharmacokinetic drug-drug interaction of pertuzumab with trastuzumab
      and docetaxel.
AB  - Pertuzumab is a novel antihuman epidermal growth factor receptor 2 (HER2)
      humanized monoclonal antibody. Combined with trastuzumab plus docetaxel,
      pertuzumab improved progression-free and overall survival versus trastuzumab plus
      docetaxel in the phase III CLEOPATRA trial (NCT00567190) in first-line HER2
      positive metastatic breast cancer. Thirty-seven patients participated in a
      pharmacokinetic (PK)/corrected QT interval substudy of CLEOPATRA, which evaluated
      potential PK drug-drug interaction (DDI). PK parameters were calculated using
      noncompartmental methods, and DDI analyses were carried out. In the presence of
      trastuzumab and docetaxel, the mean pertuzumab Cmin and Cmax in cycle 3 were 63.6
      and 183 ug/ml, respectively. The pertuzumab concentrations observed were
      consistent with simulations from a validated population PK model, indicating that
      trastuzumab and docetaxel did not alter pertuzumab PK. Comparison of geometric
      least-squares mean PK parameters between arms showed no impact of pertuzumab on
      the PK of trastuzumab or docetaxel. In conclusion, no PK DDI was observed when
      pertuzumab, trastuzumab, and docetaxel were combined for the treatment of HER2
      positive metastatic breast cancer. 

PMID- 23969514
TI  - Endoscopic characteristics and causes of misdiagnosis of intestinal
      schistosomiasis.
AB  - The aim of this study was to determine the clinical and endoscopic
      manifestations, and pathological characteristics of intestinal schistosomiasis in
      China, in order to raise awareness of intestinal schistosomiasis and prevent
      misdiagnosis and missed diagnosis. The retrospective analysis of clinical and
      endoscopic manifestations, and histopathological characteristics, were conducted
      for 96 patients with intestinal schistosomiasis. Among these patients, 21 lived
      in areas that were not infected with Schistosoma and 25 (26%) had no history of
      schistosome infection or contact with infected water. These patients were mainly
      hospitalized due to symptoms of diarrhea, mucus and bloody purulent stool.
      Sixteen cases were of the acute enteritis type, and colonoscopy results
      determined hyperaemic edema and dispersed small mucosal ulcers. The acute
      infection in patients was pathologically characterized by the deposition of
      intact ova with a large quantity of eosinocyte infiltration. Forty-one cases were
      of the chronic enteritis type which predominantly manifested with yellow nodules
      and disorder of the vascular surfaces in the intestines. Thirty-nine cases were
      diagnosed with mixed type enteritis, which demonstrated acute and chronic
      histopathological appearances. In addition, six cases of complicated colorectal
      cancer were observed. Of the 24 misdiagnosed patients, eight were misdiagnosed
      with ulcerative colitis, five with colorectal cancer, five with colorectal
      tuberculosis, four with chronic bacillary dysentery and two with irritable bowel
      syndrome. Intestinal schistosomiasis demonstrated no specific clinical or
      endoscopic manifestations and it was determined that patients with abdominal
      pain, diarrhea and mucous stool may be infected with intestinal schistosomiasis.
      Epidemiological investigations and colonoscopy combined with multi-block and
      multi-site biopsies may improve the diagnosis of intestinal schistosomiasis. In
      addition, it is necessary for intestinal schistosomiasis to be followed up by
      colonoscopy, due to its possible correlation with colorectal tumors. 

PMID- 23969515
TI  - United States pharmacopeia convention standards and clinical information for
      compounded medications used in veterinary medicine.
AB  - The United States Pharmacopeial Convention, a nongovernmental, nonprofit
      standards-setting organization, is active in the development of standards and
      information for many therapeutic ingredients and products, including compounded
      preparations utilized in human and veterinary health care. These activities are
      spearheaded by several expert committees, including Compounding Pharmacy, Sterile
      Compounding, veterinary Drugs, and Veterinary Medicine Information, with
      assistance from associated staff scientists. This article highlights the key
      processes surrounding the development of United sTates Pharmacopeial convention
      standard formulations and clinical use information for compounded medications
      used in veterineary medicine. 

PMID- 23969516
TI  - Rabbit medicine.
AB  - When filling prescriptions for a rabbit, it is important to know whether the
      rabbit is a pet or is being raised as a source of food for human consumption.
      Several drugs widely used for pet rabbits are prohibited from exralabel use in
      animals raised for food production. The list of banned drugs should always be
      perused prior to filling a prescription for a rabbit being raised for food
      production. Since no veterinary-approved products exist for rabbits and most
      medications must be compounded, pharmacists are likely to encounter prescriptions
      for rabbits in their practice. A basic understanding of rabbit anatomy, physiolgy
      and common diseases will assist pharmacists in distinguishing between safe and
      dangerous drugs for administration to rabbits. 

PMID- 23969517
TI  - The Whales: A Pharmacist's Story.
AB  - It is a daily occurrence for Grandpa's Compounding Pharmacy in Placerville,
      California, to compound preparations to meet the unique needs of individual human
      and animal patients. However, until May 2007, there had never been a request for
      compounded medications for patients weighing 12,500 pounds or 55,000 pounds! When
      two Eastern North Pacific humpback whales (mother and daughter) were traveling
      their instinctive route north to Oregon, they were for some unknown reason
      diverted into the San Fransico Bay and eventually up the Sacramento River Delta,
      where they became stranded. When it was determined by several government and
      volunteer agencies that the whales needed medical attention, Grandpa's
      Compounding Pharmacy was contacted to compound antibiotics in large quantitites
      to save these misguided sea occupants. The pharmacy rose to the challenge of what
      may have been a once-in-a-lifetime experience and successfuly compounded
      lifesaving medications for these patients in crisis. 

PMID- 23969518
TI  - Equine's Cushing's Disease: A Clinical Update.
AB  - The Department of Pharmacology at the North Carolina State University College of
      Veterinary Medicine is currently conducting stability studies of oral suspensions
      of pergolide for the treatment of Cushing's disease. While those results are not
      available at this time, this paper summarizes the results of a literature search
      on possible clinical treatments for equine Cushing's and is intended to provide
      insight into the pathophysiology of the disease. Pharmacological options for
      treatment of equine Cushing's are discussed. 

PMID- 23969519
TI  - Submitting compelling case reports for drug therapy in veterinary patients.
AB  - When peer reviewed scientific information is not available, veterinarians and
      pharmacists often turn to their colleagues seeking evidence based upon clinical
      experience in order to devise a treatment plan for a patient. Compounding
      pharmacists who provide care and compounds for veterinary patients have vast
      clinical experience of great educational value. Using specific guidelines,
      compounding pharmacists can prepare useful case reports and/or case series by
      proactively collecting clinical data, carefully selecting a case for
      presentation, and collating the details into a compelling story with a clear
      message that can survive editorial triage and contribute to the advancement of
      veterinary medical care. 

PMID- 23969520
TI  - Obtaining accreditation by the pharmacy compounding accreditation board, part 2:
      developing essential standard operating procedures.
AB  - A key component of qualifying for accreditation with the Pharmacy Compounding
      Accreditation Board is having a set of comprehensive standard operating
      procedures that are being used by the pharmacy staff. The three criteria in
      standard operating procedures for which the Pharmacy Compounding Accreditation
      Board looks are: (1)written standard operating procedures; (2)standard operating
      procedures that reflect what the organization actualy does; and (3) whether the
      written standard operating procedures are implemented. Following specified steps
      in the preparation of standard operating procedures will result in procedures
      that meet Pharmacy Compounding Accreditation Board Requirements, thereby placing
      pharmacies one step closer to qualifying for accreditation. 

PMID- 23969521
TI  - Quality-control analytical methods: a discussion of United States pharmacopeia
      chapter 71 sterility tests.
AB  - It is apparent that the quality assurance program of a compounding pharmacy
      cannot adhere to the strict requirements of some of the general chapters in the
      United States Pharmacopeia. Those chapters containing such strict requirements
      that may impact pharmacy compounding should be studied thoroughly by the
      appropriate United States Pharmacoepia expert committee. Afterward, a
      determination should be made of which standards are reasonable and which can be
      modified and implemented to ensure timely preparation of quality compounded
      medications. 

PMID- 23969522
TI  - Considerations for implementing United States pharmacopeia chapter 797
      pharmaceutical compounding-sterile preparation, part 3: risk levels.
AB  - The intent of United States Pharmacopeia Chapter 797 Pharmaceutical Compounding
      Sterile Preparations is to prevent patient harm and fatalities that may result
      from nonsterility, excessive endotoxin load, large content errors in strength of
      correct ingredients, or the presence of incorrect ingredients. Understanding the
      different microbial contamination risk levels involved in compounding sterile
      preparations, how to appropriately assign those risk levels, and the steps needed
      to maintain sterility decreases the probability of a contaminated preparation. 

PMID- 23969523
TI  - Zinc content of commercial diluents widely used in drug admixtures prepared for
      intravenous infusion.
AB  - During ongoing quality improvement efforts with two Wyeth parenteral products,
      Protonix and Zosyn, we noted that dosing solutions prepared from the products
      yielded inconsistent results on the United States Pharmacopeia Chapter 788 test
      for subvisible particulates. This manuscript discusses variables that have a
      direct impact on intravenous products meeting compendial monograph specifications
      under conditions that are encountered in the clinical setting. The rubber
      stoppers of vials used for parenteral products, different parts of commercial
      admixture bags, and the tubing of the administration sets and devices contain
      residual amounts of metal ions, plasticizers, and other additives incorparated
      for specific functions. The transition metal ions, including zinc and copper, may
      leach into drug products during manufacture and during storage of dosing
      admixture bags prepared for infusion in hospital pharmacies or clinics. The metal
      ions may compromise the quality of the infusion admixture through catalytic drug
      degradation and/or generation of undesirable metal ion complexes, which may
      convert soluble drug molecules into insoluble particulates. To preserve the
      quality of the drug product, it is essential that metal ion leachables be
      controlled proactively during manufacture of the drug product; knowledge of metal
      ion contents in the commercial diluents use for reconstitution, admixture
      preparation, and flushing of the administration lines is also critical. 

PMID- 23969524
TI  - Isoniazid release from suppositories compounded with selected bases.
AB  - There is an increasing need for an alternative route of isoniazid adminstration
      for prophylaxis and treatment of tuberculosis in children. The purpose of this
      study is to evaluate the in vitro release of isoniazid from extemporaneously
      compounded isoniazid suppositories with a goal of optimizing the suppository
      dosage form for this indication. Suppositories were compounded using three
      different base formulations (cocoa butter, Witepsol H15 Base F, and a combination
      of polyethylene glycols 3350, 1000, and 400). The release profiles of six
      compounded suppositories with isoniazid (100 mg) were tested with a United States
      Pharmacopeial Convention-approved dissolution apparatus. Isoniazid concentrations
      at predetermined time points were determined using high-performance liquid
      chromatographic analysis. The results show that drug release from the water
      solutble base (mixed polyethylene glycols) was significantly greater than that
      from the lipophilic bases (cocoa butter and Witepsol H15). The percentage of
      isoniazid release form the polyethylene glycol suppository formulation (70 +/-
      1.4 mg/mL) was greater than that from the cocoa butter (55 +/- 1.1 mg/mL) and
      Witepsol H15 Base F (18 +/- 0.36 mg/mL) suppository formulations. 

PMID- 23969525
TI  - Post Scription: Thousands of Unapproved New Drugs are on the U.S. Market, Part 2.

PMID- 23969526
TI  - Hyaluronan degrading silica nanoparticles for skin cancer therapy.
AB  - We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced
      adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal
      was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific
      activity of the enzyme via the layer-by-layer self-assembly technique. This
      process was characterized by dynamic light scattering (DLS), zeta potential,
      infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and
      enzymatic activity measurements. The nanoparticles were tested in vivo as
      adjuvants of carboplatin (CP), peritumorally injected in A375 human melanoma
      bearing mice and compared with the non-immobilized enzyme, on the basis of equal
      enzymatic activity. Alcian Blue staining of A375 tumors indicated large
      overexpression of hyaluronan. At the end of the experiment, tumor volume
      reduction with SiNP-immobilized Hyal was significantly enhanced compared to non
      immobilized Hyal. Field emission scanning electron microscopy (FE-SEM) images
      together with energy dispersive X-ray spectroscopy (EDS) spectra confirmed the
      presence of SiNP on the tumor. We mean a proof of concept: this extracellular
      matrix (ECM) degrading enzyme, immobilized on SiNP, is a more effective local
      adjuvant of cancer drugs than the non-immobilized enzyme. This could prove useful
      in future therapies using other or a combination of ECM degrading enzymes. 

PMID- 23969527
TI  - Association between idiopathic hearing loss and mitochondrial DNA mutations: a
      study on 169 hearing-impaired subjects.
AB  - Mutations in mitochondrial DNA (mtDNA) have been shown to be an important cause
      of sensorineural hearing loss (SNHL). In this study, we performed a clinical and
      genetic analysis of 169 hearing-impaired patients and some of their relatives
      suffering from idiopathic SNHL, both familial and sporadic. The analysis of four
      fragments of their mtDNA identified several polymorphisms, the well known
      pathogenic mutation, A1555G, and some novel mutations in different genes,
      implying changes in the aminoacidic sequence. A novel sporadic mutation in 12S
      rRNA (MT-RNR1), not previously reported in the literature, was found in a case of
      possible aminoglycoside-induced progressive deafness.

PMID- 23969528
TI  - Neuroprotein dynamics in the cerebrospinal fluid: intraindividual concomitant
      ventricular and lumbar measurements.
AB  - OBJECTIVE: The measurement of neuromarker/neuroproteins in the cerebrospinal
      fluid (CSF) is gaining increased popularity. However, insufficient information is
      available on the rostrocaudal distribution of neuroproteins in the CSF to
      guarantee an appropriate interpretation of ventricular versus lumbar
      concentrations. METHODS: In 10 patients treated with both an external ventricular
      and a lumbar CSF drain, we collected concomitant CSF samples. We measured CSF
      concentrations of the glial S100B protein, the neuron-specific enolase (Cobas
      e411(r); Roche Diagnostics), the leptomeningeal beta-trace protein (BN Pro
      Spec(r); Dade Behring/Siemens), and the blood-derived albumin (Immage; Beckman
      Coulter). Statistical analysis was performed with a paired Wilcoxon signed ranks
      test. RESULTS: In patients with a free CSF circulation without any recent
      neurosurgical procedure, S100B and neuron-specific enolase concentrations did not
      differ between the ventricular and lumbar CSF while beta-trace and albumin levels
      were significantly higher in the lumbar than in the ventricular CSF (p=0.008 and
      p=0.005). Following posterior fossa tumor surgery, all proteins accumulate in the
      lumbar CSF. CONCLUSION: For brain-derived proteins, we could not confirm a
      rostrocaudal CSF gradient while lepto-meningeal and blood-derived proteins
      accumulate in the lumbar CSF. We conclude that for the interpretation of protein
      CSF concentrations, the source of the sample is of crucial importance.

PMID- 23969529
TI  - Bioorthogonal labelling of biomolecules: new functional handles and ligation
      methods.
AB  - This review provides a literature overview of bioorthogonal ligation methods for
      protein modification, which have largely evolved over the last 15 years. Since
      1990, various new reactions have been developed that do not involve naturally
      occurring functional handles. Especially the development of such so-called
      bioorthogonal ligations has significantly contributed to our ability to
      selectively modify biomolecules not only in the test tube, but also in living
      systems. 

PMID- 23969530
TI  - Inhibition of MMP-9 using a pyrrole-imidazole polyamide reduces cell invasion in
      renal cell carcinoma.
AB  - We investigated the clinical significance of the expression levels of matrix
      metalloproteinase 9 (MMP-9) in renal cell carcinoma (RCC). In addition, we
      validated the efficacy of pyrrole imidazole polyamide (PIP) targeting MMP-9 on
      inhibiting proliferation and invasion of RCC. We evaluated the expression levels
      of MMP-9 in 249 RCC specimens by immunostaining and analyzed the association
      between MMP-9 expression levels and cancer-specific survival. Furthermore, in a
      human RCC cell line, Caki-2, we tested the effect of a couple of PIPs targeting
      MMP-9 one recognizing an NF-kappaB binding site (MMP-9-NF-kappaB PIP) and another
      for the AP-1 binding site (MMP-9-AP-1 PIP) in the MMP-9 promoter. The expression
      levels of MMP-9, proliferative activity and invasive capability were tested by
      quantitative PCR, WST8 assay and Matrigel invasion assay, respectively. By
      immunostaining of the clinical specimens, strong MMP-9 staining was proven to be
      a significant predictor of poor prognosis for cancer-specific survival (P<0.01).
      In Caki-2 cells, MMP-9-NF-kappaB PIP significantly reduced the expression levels
      of MMP-9 mRNA and inhibited cell invasion, but did not affect the cell
      proliferation activity. On the other hand, no effect was found in MMP-9-AP-1 PIP
      on MMP-9 mRNA expression, cell proliferation and invasion. We confirmed the
      inhibitory effects of MMP-9-NF-kappaB PIP on the expression of MMP-9 and
      subsequent invasion of Caki-2 cells. Since it was clearly shown that high MMP-9
      expression levels were associated with poor prognosis of RCC, MMP-9 is a
      potential candidate target for RCC treatment. Transcription therapy using a minor
      groove binder, such as NF-kappaB PIP, may be a potential therapeutic agent for
      RCC, although further investigation is required. 

PMID- 23969531
TI  - Rearrangement of atrial bundle architecture and consequent changes in anisotropy
      of conduction constitute the 3-dimensional substrate for atrial fibrillation.
AB  - BACKGROUND: Anisotropy of conduction facilitates re-entry and is, therefore, a
      key determinant of the stability of atrial fibrillation (AF). Little is known
      about the effect of AF on atrial bundle architecture and consequent changes in
      anisotropy of conduction and maintenance of AF. METHODS AND RESULTS: Direct
      contact mapping was performed in left atria of goats with acute AF (n=6) or
      persistent AF (n=5). The degree and direction of anisotropic conduction were
      analyzed. Mapped tissue regions were imaged by high-resolution MRI for
      identification of endocardial and epicardial bundle directions. Correlation
      between endocardial and epicardial bundle directions and between bundle
      directions and anisotropic conduction was quantified. In persistent AF,
      epicardial bundles were oriented more perpendicularly to endocardial bundles than
      in acute AF (% angles<20 degrees  between epicardial and endocardial bundle
      directions were 7.63% and 21.25%, respectively; P<0.01). In acute AF, the
      direction of epicardially mapped anisotropic conduction correlated with
      endocardial but not with epicardial bundles. In persistent AF, the direction of
      anisotropic conduction correlated better with epicardial than with endocardial
      bundles (% angles<20 degrees  between direction of anisotropic conduction and
      bundle direction were 28.77% and 18.45%, respectively; P<0.01). CONCLUSIONS:
      During AF, atrial bundle rearrangement manifests itself in more perpendicular
      orientation of epicardial to endocardial bundles. Propagation of fibrillation
      waves is dominated by endocardial bundles in acute AF and by epicardial bundles
      in persistent AF. Together with the loss of endo-epicardial electrical
      connections, rearrangement of atrial bundles underlies endo-epicardial
      dissociation of electrical activity and the development of a 3-dimensional AF
      substrate.

PMID- 23969532
TI  - Analysis of serum gamma-glutamyl transferase levels in neonatal intensive care
      unit patients.
AB  - OBJECTIVES: Gamma-glutamyl transferase (GGT) is commonly measured in newborn
      infants as a sensitive liver function test; however, reference ranges are mostly
      based on early studies, including relatively small number of patients. The aim of
      this study was to emphasise recently changed GGT values because of changed
      newborns profile admitted to neonatal intensive care units (NICUs) and establish
      new cross-sectional reference ranges for the serum GGT levels in a cohort of
      neonates between 26 and 42 weeks' gestational age in 1 centre. METHODS: From
      January 1, 2010 to December 31, 2012, liver function tests including serum GGT
      measurements were performed in 705 newborns who were admitted to NICUs because of
      different aetiologies at Gazi University School of Medicine Hospital, Ankara,
      Turkey. Infants with Apgar score <8 at the fifth minute, any metabolic or liver
      disease, cholestasis, congenital infection, culture-proven sepsis, elevated serum
      aminotransferases, and who were treated with phenobarbital were excluded.
      Clinical and laboratory data of 583 neonates were analysed retrospectively. GGT
      was measured by enzymatic method using the Abbott Architect C16000 autoanalyser.
      Mean, 2.5th, and 97.5th percentiles were used to express the reference range
      data. RESULTS: Four hundred sixty-one GGT values of 200 preterm infants and 501
      GGT values of 383 term infants during the first 28 days after birth were
      analysed. Serum GGT levels of preterm infants in the first 7 days and between 8
      and 28 days after delivery were (mean+/-standard deviation; 141.81+/-88.56 U/L
      and 131.17+/-85.53 U/L) similar to term infants (139.90+/-86.46 U/L and 144.56+/
      86.51 U/L), respectively (P=0.649 and P=0.087). Serum GGT levels were found to be
      significantly higher in male infants (no need of query) (145.98+/-93.68 U/L) than
      female infants (132.18+/-78.97 U/L) (P=0.035), and infants born vaginally
      (152.24+/-90.71 U/L) also had higher serum GGT activity than those born by
      caesarean section (135.38+/-85.37 U/L) (P=0.005). CONCLUSIONS: A new reference
      range for serum GGT levels that is higher than previous reference values can
      identify neonates with truly abnormal results and prevent unnecessary
      interventions.

PMID- 23969533
TI  - Calretinin, beta-tubulin immunohistochemistry, and submucosal nerve trunks
      morphology in Hirschsprung disease: possible applications in clinical practice.
AB  - OBJECTIVES: The aim of this study was to investigate calretinin and beta-tubulin
      immunohistochemical expression together with submucosal nerve trunks morphology
      in differently innervated segments of Hirschsprung disease (HD) and total colonic
      aganglionosis (TCA). METHODS: A total of 25 cases (22 HD, 3 TCA) and 18 controls
      were processed for calretinin and beta-tubulin immunohistochemistry. Sections
      representative of distal aganglionic, transition, and proximal ganglionic
      segments were evaluated by a visual grading score; beta-tubulin was evaluated
      also by image analysis. Submucosal nerve trunks hypertrophy and hyperplasia were
      measured by citomorphology. The length of proximal segment was correlated to
      postoperative bowel function. RESULTS: Controls showed intense calretinin and
      beta-tubulin staining. In HD and TCA, calretinin staining was related to the
      presence of ganglion cells: negative in distal, faint in transition, intense in
      proximal segment. beta-Tubulin staining was weak in all of the segments of HD and
      negative in TCA. Hypertrophic and hyperplastic nerve trunks characterized
      aganglionic segment, and progressively decreasing nerve size was observed in
      transition and ganglionic segments. Transient postoperative constipation,
      soiling, or enterocolitis was present in 59% of patients with HD without clear
      relation to proximal segment length or presence of hypertrophic nerve trunks.
      CONCLUSIONS: Calretinin is a reliable marker of the presence of ganglion cells,
      and, together with nerve hypertrophy, it helps to identify the transition zone.
      Length and nerve size of proximal segment in resected specimen did not affect the
      postsurgical intestinal function. Reduced beta-tubulin expression along the
      entire colonic tract, included proximal ganglionic segments, may represent a
      potential impairing factor for the enteric neural transmission.

PMID- 23969534
TI  - Isolated autoimmune enteropathy associated with autoantibodies to a novel 28-kDa
      duodenal antigen.

PMID- 23969536
TI  - Validation of ultrasound methods to monitor gastric volume changes in preterm
      infants.
AB  - OBJECTIVES: The aim of this study was to validate 4 sonographic methods of
      estimating stomach volume for the purpose of monitoring changes in gastric volume
      over time and to describe the echogenic characteristics of milk feeds. METHODS:
      Twenty-four infants were monitored during a single intragastric tube feed, with 2
      ultrasound images of the entire stomach and an image of the antral cross
      sectional area (ACSA) before, during, and after the feed. Raw measurements, 3
      stomach volume calculations, and ACSA were tested for intra- and interrater
      agreement. Calculated stomach volumes and ACSA were compared with delivered feed
      volumes, and characteristics of stomach image echogenicity graded at each time
      point. RESULTS: Spheroid calculation of stomach volume was the most reliable and
      valid measure of stomach volume. Fortified breast milk feeds were more echogenic
      than unfortified breast milk feeds. Residual stomach volumes (median 2.12 mL,
      range 0.59-9.27 mL) were identified in 18 of 24 infants. CONCLUSIONS: Direct
      ultrasound stomach measurement (spheroid) will provide a useful research tool and
      a potential clinical tool for assessing gastric emptying and feeding intolerance
      in preterm infants.

PMID- 23969535
TI  - Assessing psychosocial risk in pediatric inflammatory bowel disease: validation
      of the Psychosocial Assessment Tool 2.0_General.
AB  - AIM: The aim of this study was to present the preliminary psychometric properties
      of the Psychosocial Assessment Tool 2.0_General (PAT2.0_GEN), a brief screener
      for psychosocial risk in families of children with inflammatory bowel disease
      (IBD). METHODS: Caregivers of 42 youth with IBD were recruited and administered a
      battery of measures including the PAT2.0_GEN and well-validated measures of child
      emotional and behavioral functioning at baseline and at a 6-month follow-up.
      RESULTS: Internal consistency for the PAT2.0_GEN total score was good
      (alpha=0.82). Baseline was significantly associated with the 6-month follow-up
      (r=0.79, P<0.001). Significant correlations between the baseline PAT2.0 _GEN
      total score and caregiver-reported Child Behavior Checklist total scores at
      baseline (r=0.74, P<0.001) and at a 6-month follow-up (r=0.62, P<0.001) support
      the content and predictive validity of the PAT2.0_GEN. Baseline PAT2.0_GEN was
      also significantly correlated with youth-reported Child Behavior Checklist total
      scores at baseline (r=0.37, P=0.02) but not at the 6-month follow-up (r=0.23,
      P=0.17). CONCLUSIONS: A number of indicators support the concurrent and
      predictive utility of the PAT2.0_GEN. The PAT2.0_GEN is a promising tool for
      screening psychosocial risk that could facilitate the provision of psychosocial
      services to those patients most in need.

PMID- 23969537
TI  - Feeding immaturity in preterm neonates: risk factors for oropharyngeal aspiration
      and timing of maturation.
AB  - OBJECTIVE: Oropharyngeal aspiration (OPA) is a common cause of morbidity in
      premature neonates. We sought to identify significant risk factors and determine
      the timing of feeding maturation in preterm infants with OPA. METHODS: We
      performed a retrospective medical record review of 148 former preterm neonates
      referred for modified barium swallow study (MBSS) during a 3-year period. We
      looked at the MBSS results and potential clinical and demographic risk factors
      and performed bivariate and multivariable logistic regression analyses to
      evaluate predictors of failure. We evaluated the timing of resolution of OPA
      based on MBSS results. RESULTS: Of the 148 infants comprising our study cohort,
      47 (32%) passed their initial MBSS and 101 (68%) were found to aspirate thin
      liquids. Infants who aspirate had younger corrected gestational age (CGA) and
      postnatal age at the time of testing. Increasing CGA led to lower odds of
      failing. Infants passed a MBSS at a median CGA of 53 weeks and those who failed
      an initial MBSS eventually passed after a median of ~3.4 months from the first
      study. Infants with bronchopulmonary dysplasia had lower odds of failing their
      MBSS (odds ratio 0.16), but those taking inhaled corticosteroids and diuretics
      had higher odds of failing, and infants who were multiples also had higher odds
      of failing. CONCLUSIONS: We determined the median CGA for passing MBSS and
      identified risk factors for OPA in this population. This information can help
      guide providers when counseling families on timing of feeding maturity and
      anticipation of appropriate timing for follow-up MBSS testing.

PMID- 23969538
TI  - Obesity and symptomatic cholelithiasis in childhood: epidemiologic and case
      control evidence for a strong relation.
AB  - OBJECTIVES: The aims of this study were to correlate the temporal trends in
      obesity prevalence with hospitalization rates for symptomatic cholelithiasis and
      to estimate the strength of the association between obesity and symptomatic
      cholelithiasis in patients hospitalized at an urban children's hospital in New
      York serving a multiethnic population. METHODS: Using obesity prevalence data
      from the National Health and Nutrition Examination Survey and the rates of
      hospitalization for cholelithiasis derived from the Kids' Inpatient Database for
      1997-2007, we estimated a correlation and a linear regression. We conducted a
      retrospective, case-control study in which each case ages 4 to 20 years with
      symptomatic cholelithiasis was individually matched to a control admitted with
      appendicitis based on age, sex, ethnicity, and race. RESULTS: The prevalence of
      obesity and the cholelithiasis hospitalization rate increased over time (R=0.87,
      P=0.0025). For every 1% increase in the obesity rate among children, the rate of
      hospitalization for gallstones increased by 0.65/100,000 children (R2=0.75,
      P=0.0025, 95% confidence interval [CI] 0.32-0.99). The odds ratio for obesity in
      cases versus controls was 5.78 (n=518, P<0.0001, 95% CI 3.50-9.53). We found a
      significant dose-response effect, which showed that for every 1 z score increase
      in body mass index, the risk of cholelithiasis was increased by 79% (P<0.0001,
      95% CI 1.5-2.13). CONCLUSIONS: The national trend in the prevalence of obesity
      from 1997 to 2009 was significantly correlated with increasing rates of
      hospitalization for pediatric cholelithiasis. Our case-control study suggests
      that obesity is a significant risk factor for hospital admission because of
      cholelithiasis.

PMID- 23969539
TI  - Nonsteroidal anti-inflammatory drug-induced vanishing bile duct syndrome treated
      with plasmapheresis.

PMID- 23969540
TI  - Atypical manifestation of carnitine palmitoyltransferase 1A deficiency:
      hepatosplenomegaly and nephromegaly.

PMID- 23969542
TI  - Eosinophilic esophagitis in a child with juvenile polyposis syndrome: is there a
      link?

PMID- 23969541
TI  - Humoral immune mechanism of liver injury in giant cell hepatitis with autoimmune
      hemolytic anemia.
AB  - BACKGROUND AND AIMS: Giant cell hepatitis with autoimmune hemolytic anemia (GCH
      AHA) is presumed to be an autoimmune disease, but the mechanism of liver injury
      is unknown. We proposed that in CGH-AHA, the humoral limb of autoimmunity is the
      dominant force driving progressive liver injury. METHODS: We studied 6 cases of
      GCH-AHA and 6 cases of autoimmune hepatitis (AIH) with early childhood onset (3
      type 1 and 3 type 2). Liver biopsies were graded for portal and periportal
      inflammation and for giant cells. Immunohistochemistry characterized cellular
      inflammation and complement involvement in injury by showing C5b-9 complex in
      hepatocytes. RESULTS: Clinical and biochemical features at presentation were
      generally similar; however, the absence of autoantibodies and the presence of
      Coombs positivity did distinguish GCH-AHA from early-onset AIH. Liver biopsy
      pathology in CGH-AHA showed giant cells and little inflammation, whereas AIH
      showed the opposite. C5b-9 staining showed high-grade complement-mediated pan
      lobular hepatocyte injury in all of the cases with GCH-AHA, whereas little C5b-9
      was seen in hepatocytes in cases with AIH. Inflammation in GCH-AHA comprised
      mainly lobular macrophages and neutrophils, whereas portal and periportal T-cell
      and B-cell inflammation characterized cases with AIH. Most cases with AIH
      responded to therapy with prednisone and azathioprine, whereas most cases with
      GCH-AHA responded only to rituximab. CONCLUSIONS: Widespread complement-mediated
      hepatocyte injury and typical C3a and C5a complement-driven liver inflammation
      along with Coombs-positive hemolytic anemia in GCH-AHA provide convincing
      evidence that systemic B-cell autoimmunity plays a central pathologic mechanism
      in the disease. Our findings support B-cell-directed immunotherapy as a first
      line treatment of GCH-AHA.

PMID- 23969543
TI  - A versatile chemical tool for the preparation of conductive graphene-based
      polymer nanocomposites.
AB  - A general route for the functionalization of graphene and graphene derivatives
      with a low molecular weight polymer by thiol-radical reactions is reported.
      Polymer-modified graphene is employed as a filler for high density polyethylene
      to generate materials with good electrical conductivity. 

PMID- 23969544
TI  - Spinal tuberculosis: which is the best surgical approach?

PMID- 23969545
TI  - Phosphoinositide 3-kinase delta/gamma inhibition does not prevent concanavalin A
      induced hepatitis.
AB  - An increasing number of studies have suggested that phosphoinositide 3-kinase
      gamma (PI3Kgamma) and PI3Kdelta are involved in the pathogenesis of autoimmune
      and inflammatory diseases, such as asthma and atherosclerosis. However, the
      underlying mechanism of acute hepatitis remains unknown. The present study aimed
      to determine the effect of PI3Kdelta/gamma inhibition on hepatic injury in a
      murine model of hepatitis induced by concanavalin A (ConA). It was demonstrated
      that the pharmacological inhibition of PI3Kdelta/gamma by TG100-115 did not
      prevent liver damage following ConA challenge. Furthermore, the PI3Kdelta/gamma
      inhibition resulted in elevated transaminase activity in the serum, aggravated
      hepatic lesions characterized by hepatic necrosis, increased inflammatory cell
      infiltration and apoptosis of hepatocytes. Survival tests demonstrated that TG100
      115 significantly increased the death rate of mice following ConA challenge. In
      addition, TG100-115 increased the serum levels of the proinflammatory cytokine IL
      2 following ConA injection. These results may oppose the development of
      PI3Kdelta/gamma inhibitors as therapeutic agents, particularly for the treatment
      of human hepatitis.

PMID- 23969546
TI  - Bilateral masseter and internal pterygoid muscle hypertrophy: a diagnostic
      challenge.
AB  - OBJECTIVE: To describe an unusual case of bilateral masseter and pterygoid muscle
      hypertrophy. CLINICAL PRESENTATION AND INTERVENTION: A 53-year-old female patient
      presented with a bilateral, painless swelling at the parotid areas without
      improvement after using antibiotics/systemic corticosteroids/nonsteroidal anti
      inflammatory agents. Her medical history included thyroid nodules, but no
      dental/occlusal disorders were observed. The initial differential diagnosis
      included salivary gland/jaw bone/masseter pathology, but the CT/MRI revealed only
      an increase in the size of the masseter and pterygoid muscles. The patient was
      informed of the benign nature of the swelling and was advised to discontinue the
      use of nonsteroidal anti-inflammatory agents. CONCLUSION: The bilateral
      hypertrophy of masseter muscles should be considered in differential diagnosis in
      cases of unilateral or bilateral swelling of the parotid or lateral mandible
      area.

PMID- 23969547
TI  - Paper-based electroanalytical devices with an integrated, stable reference
      electrode.
AB  - This paper describes the development of a referenced Electrochemical Paper-based
      Analytical Device (rEPAD) comprising a sample zone, a reference zone, and a
      connecting microfluidic channel that includes a central contact zone. We
      demonstrated that the rEPADs provide a simple system for direct and accurate
      voltammetric measurements that are referenced by an electrode with a constant,
      well-defined potential. The performance of the rEPADs is comparable to commercial
      electrochemical cells, and the layout can be easily integrated into systems that
      permit multiplexed analysis and pipette-free sampling. The cost of this portable
      device is sufficiently low that it could be for single-use, disposable
      applications, and its method of fabrication is compatible with that used for
      other paper-based systems. 

PMID- 23969548
TI  - Kidney attack: overdiagnosis of acute kidney injury or comprehensive definition
      of acute kidney syndromes?

PMID- 23969550
TI  - Sex-specific differences in the development of acute alcohol-induced liver
      steatosis in mice.
AB  - AIMS: Results of several animal studies suggest that similar to humans, female
      rodents are more susceptible to chronic alcohol-induced liver disease (ALD). The
      aim of the present study was to determine whether female mice are more
      susceptible to acute alcohol-induced steatosis than male mice and to investigate
      possible mechanisms involved. METHODS: Male and female C57BL/6J mice received one
      single dose of ethanol (6 g/kg bodyweight) or isocaloric maltose-dextrin solution
      intragastrically. Plasma alcohol concentration, markers of hepatic steatosis,
      activation of the TLR-4 signaling cascade and triglyceride export as well as
      lipid peroxidation and of iron metabolism were measured 12 h after acute alcohol
      intake. RESULTS: In male and female ethanol-treated mice, plasma alcohol
      concentrations were still markedly increased 12 h after the alcohol challenge,
      which was associated with a significant accumulation of lipids in the liver and
      increase of transaminases in plasma; however, lipid accumulation was ~3-fold
      higher in females in comparison with male animals. Expression of MyD88 was only
      found to be significantly induced in livers of female alcohol-exposed mice,
      whereas protein levels of ApoB were found to be significantly lower only in
      livers of female mice exposed to ethanol. Levels of 4-HNE protein adducts and
      ferritin were induced in livers of male and female ethanol-treated mice.
      CONCLUSION: Taken together, these data suggest that female mice are also more
      susceptible to acute alcohol-induced liver steatosis and that this involves an
      increased activation of TLR-4-dependent signaling pathways in the liver.

PMID- 23969551
TI  - Chronic excessive alcohol consumption and male fertility: a case report on
      reversible azoospermia and a literature review.
AB  - AIMS: The aim of this work was to report on a heavy drinker whose azoospermia was
      reversed after alcohol withdrawal. We also review the literature on links between
      alcohol consumption and azoospermia. METHOD: This study is a clinical case report
      and a literature review. RESULTS: Two years after alcohol withdrawal, a child was
      born following assisted reproduction technique. Excessive alcohol consumption
      (i.e. more than 60 g a day) is strongly associated with azoospermia and this
      condition may be reversible after alcohol withdrawal. CONCLUSIONS: Testicular
      biopsies should be countra-indicated for heavy drinkers, and in order to increase
      the chances of obtaining a pregnancy, alcohol abstinence should be encouraged in
      male with low-to-moderate alcohol intakes.

PMID- 23969552
TI  - Blood ethanol levels of nonabstinent Japanese alcoholic men in the morning after
      drinking and their ADH1B and ALDH2 genotypes.
AB  - AIMS: Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B, rs1229984) and
      aldehyde dehydrogenase-2 (ALDH2, rs671) affect ethanol (EtOH) metabolism and
      susceptibility to alcoholism. METHODS: We evaluated associations between
      ADH1B/ALDH2 genotypes and the blood EtOH levels of 805 Japanese alcoholic men in
      the morning after they had drunk within the previous 34 h. RESULTS: Age-adjusted
      usual alcohol consumption did not differ according to ADH1B/ALDH2 genotypes.
      Higher blood EtOH levels persisted for longer periods in the ADH1B*1/*1 carriers
      (n = 246) than in the ADH1B*2 carriers (n = 559). Blood EtOH levels did not
      differ by ALDH2 genotype. The blood EtOH levels >= 0.3 mg/ml (criterion for drunk
      driving in Japanese law) were observed (40% vs. 14-17%, P < 0.0001) in a higher
      proportion of the ADH1B*1/*1 carriers than of the ADH1B*2 carriers after a 12.1
      to-18-h interval since the last drink. Multivariate analyses showed that the EtOH
      levels heightened by 0.500 mg/ml in the presence of ADH1B*1*1 and by 0.248 mg/ml
      in the presence of cirrhosis, and lowered by 0.120 mg/ml per 10-year age
      increase, by 0.087 mg/ml per 10-kg body-weight increase and by 0.673 mg/ml per 10
      h interval since the last drink. The odds ratio (95% confidence interval) for an
      EtOH level >= 0.3 mg/ml was 3.44 (2.34-5.04) in the presence of ADH1B*1/*1, 2.01
      (1.28-3.14) in the presence of cirrhosis, 0.59 (0.49-0.71) per 10-year age
      increase, 0.80 (0.68-0.95) per 10-kg body-weight increase and 0.10 (0.07-0.15)
      per 10-h interval since the last drink. CONCLUSION: The longer-than-expected EtOH
      lingering in the blood of the ADH1B*1/*1 alcoholics may exacerbate alcohol
      related problems, including drunk driving.

PMID- 23969553
TI  - Retraction: Biochemical predictors of delirium tremens in patients in alcohol
      withdrawal.

PMID- 23969554
TI  - Study of immunogenicity of recombinant proteins based on hemagglutinin and
      neuraminidase conservative epitopes of influenza A virus.
AB  - BACKGROUND: Recombinant hemagglutinin (rHA) and neurominidase (rNA) developed in
      our investigation are amino acid sequence consensus variants of H1N1 2009 subtype
      influenza virus strain, also including immunogenic epitopes typical for other
      influenza virus subtypes (H3N1 and H5N1). Substitutions were made: typical for
      Russian virus isolates (in HA - S220T, NA - D248N) and in active centers of
      molecules - R118L, R293L, R368L; C92S, C417S to increase recombinant proteins
      stability in E. coli. The aim of the present work was to study immunogenicity of
      the obtained rHA and rNA. MATERIAL AND METHODS: Fragments aa 83-469 of NA and aa
      61-287 of HA were chosen because they include the main B-cell epitopes and are
      the minimal structures for correct folding of target proteins. The designed
      nucleotide sequences were synthesized and purified and the expression of rNA and
      rNA were analyzed. For immunization and virus challenge we used influenza viruses
      A/California/04/2009 (H1N1), A/PR/8/34 (H1N1), A/Perth/16/2009 (H3N2),
      A/Chicken/Kurgan/05/2005 R.G. (H5N1), and B/Florida/04/2006. Specific IgG levels
      were determined by ELISA in 96-well ELISA plates. Significant differences of
      survival in mouse groups were analyzed by Mantel-Cox (log-rank) and Gehan-Breslow
      Wilcoxon tests. RESULTS: The obtained results demonstrate the high immunogenicity
      and ability of indicated proteins mixture to provide similar cross-protection
      against influenza viruses of the H1N1 subtype. CONCLUSIONS: The data obtained
      suggest efficient pluripotent vaccine creation based on HA and NA conservative
      regions.

PMID- 23969555
TI  - Transcriptome analysis of murine thymic epithelial cells reveals age-associated
      changes in microRNA expression.
AB  - Age-related thymic involution is accompanied by a decrease in thymopoiesis and,
      thus, a deficiency in T cell-mediated immunity in the elderly. A number of events
      involved in thymic involution have been discovered; however, it remains unclear
      as to whether they are causes or consequences of thymic involution. These events
      include the degeneration of T cell progenitors, as well as the deterioration of
      the thymic stroma, which is a characteristic of thymic epithelial cell loss due
      to increased apoptosis and decreased cell proliferation. MicroRNAs (miRNAs) are
      believed to play important roles in the regulation of cell death and
      proliferation during the aging process. In the present study, we compared the
      transcriptional levels of various miRNAs in TECs from young and aged mice using
      microarray analysis. Quantitative PCR was performed to confirm the changes in the
      expression of miRNAs in the different age groups. Possible downstream targets and
      pathways of these miRNAs were predicted by performing bioinformatics analysis. To
      the best of our knowledge, this is the first study to systematically analyze the
      expression of miRNAs in mouse TECs and to demonstrate that miRNA expression is
      altered with thymic aging.

PMID- 23969556
TI  - Analog restless legs syndrome rating scale.
AB  - We propose an analog restless legs syndrome (RLS) rating scale (ARLS) to assess
      RLS severity. ARLS has three components: overall perceived severity of symptoms,
      the severity of urge to move and the degree to which symptoms improve with
      movement, each scored from 0 to 100. ARLS is relatively convenient, easy to
      administer in clinics and can be rapidly assessed. Our goal was to compare the
      novel ARLS with the well-known International RLS Study Group scale (IRLS) to
      assess the efficacy of the ARLS. ARLS and IRLS were administered on 93 occasions.
      Perceived severity of the disease measured with ARLS positively correlated with
      the normalized IRLS score (correlation coefficient 0.6; slope 1.2; p<0.0001).
      Improvement in symptoms after movement inversely correlated with the disease
      burden as measured with normalized IRLS score (slope -0.94; correlation
      coefficient 0.4; p=0.0001). For both low and high IRLS scores, the urge to move
      measured with ARLS saturated, suggesting a non-linear, multifactorial
      relationship between the perception of RLS severity and the urge to move. In
      conclusion, individual components of the ARLS correlated well with total IRLS
      score. We emphasize that the ARLS is a simple RLS rating tool that can be used in
      clinical settings.

PMID- 23969557
TI  - Long-term growth under elevated CO2 suppresses biotic stress genes in non
      acclimated, but not cold-acclimated winter wheat.
AB  - This study compared the photosynthetic performance and the global gene expression
      of the winter hardy wheat Triticum aestivum cv Norstar grown under non-acclimated
      (NA) or cold-acclimated (CA) conditions at either ambient CO2 or elevated CO2. CA
      Norstar maintained comparable light-saturated and CO2-saturated rates of
      photosynthesis but lower quantum requirements for PSII and non-photochemical
      quenching relative to NA plants even at elevated CO2. Neither NA nor CA plants
      were sensitive to feedback inhibition of photosynthesis at elevated CO2. Global
      gene expression using microarray combined with bioinformatics analysis revealed
      that genes affected by elevated CO2 were three times higher in NA (1,022 genes)
      compared with CA (372 genes) Norstar. The most striking effect was the down
      regulation of genes involved in the plant defense responses in NA Norstar. In
      contrast, cold acclimation reversed this down-regulation due to the cold
      induction of genes involved in plant pathogenesis resistance; and cellular and
      chloroplast protection. These results suggest that elevated CO2 has less impact
      on plant performance and productivity in cold-adapted winter hardy plants in the
      northern climates compared with warmer environments. Selection for cereal
      cultivars with constitutively higher expression of biotic stress defense genes
      may be necessary under elevated CO2 during the warm growth period and in warmer
      climates. 

PMID- 23969558
TI  - Theophylline-dependent riboswitch as a novel genetic tool for strict regulation
      of protein expression in Cyanobacterium Synechococcus elongatus PCC 7942.
AB  - The cyanobacterium Synechococcus elongatus PCC 7942 is a major model species for
      studies of photosynthesis. It is are also a potential cell factory for the
      production of renewable biofuels and valuable chemicals. We employed engineered
      riboswitches to control translational initiation of target genes in this
      cyanobacterium. A firefly luciferase reporter assay revealed that three
      theophylline riboswitches performed as expected in the cyanobacterium. Riboswitch
      E* exhibited very low leaky expression of luciferase and superior and dose
      dependent on/off regulation of protein expression by theophylline. The maximum
      magnitude of the induction vs. basal level was ~190-fold. Furthermore, the
      induction level was responsive to a wide range of theophylline concentrations in
      the medium, from 0 to 2 mM, facilitating the fine-tuning of luciferase
      expression. We adapted this riboswitch to another gene regulation system, in
      which expression of the circadian clock kaiC gene product is controlled by the
      theophylline concentration in the culture medium. The results demonstrated that
      the adequately adjusted expression level of KaiC restored complete circadian
      rhythm in the kaiC-deficient arrhythmic mutant. This theophylline-dependent
      riboswitch system has potential for various applications as a useful genetic tool
      in cyanobacteria. 

PMID- 23969559
TI  - Human dendritic cells transfected with a human papilloma virus-18 construct
      display decreased mobility and upregulated cytokine production.
AB  - The marked depletion of dendritic cells (DCs) in skin cancers, as well as
      preneoplastic and neoplastic cervical epithelium, suggests a central role for DCs
      in productive human papillomavirus (HPV) infection and cancer promotion. It has
      been suggested that HPV may facilitate tumor development by reducing DC density,
      contributing to a decrease in local immune surveillance. In this study, we have
      examined the response of human DCs transfected with a construct containing the
      HPV18 genome and their subsequent expression of papilloma virus proteins.
      Transfected cells expressed the L1 major capsid protein and upregulated E6 and E7
      oncoprotein transcripts as detected by RT-PCR. Transfection of DCs also resulted
      in a significant increase in cytokine production. Finally, we observed that HPV18
      transfection decreased the migratory activity of DCs. Our data indicate that HPV
      transfection of DCs leads to changes in migratory activity and cytokine
      production, which potentially can suppress or delay immune responses to viral
      antigens. Additionally, changes in cytokine production by HPV-transformed human
      fibroblasts and human cervical epithelial cells revealed that the migratory and
      antigen-presenting functions of DCs may be impaired by the suppressive effects of
      cytokines produced by HPV-infected epithelial and stromal cells. 

PMID- 23969560
TI  - Prostacyclin regulates spinal nociceptive processing through cyclic adenosine
      monophosphate-induced translocation of glutamate receptors.
AB  - BACKGROUND: Prostacyclin (PGI2) is known to be an important mediator of
      peripheral pain sensation (nociception) whereas little is known about its role in
      central sensitization. METHODS: The levels of the stable PGI2-metabolite 6-keto
      prostaglandin F1alpha (6-keto-PGF1alpha) and of prostaglandin E2 (PGE2) were
      measured in the dorsal horn with the use of mass spectrometry after peripheral
      inflammation. Expression of the prostanoid receptors was determined by
      immunohistology. Effects of prostacyclin receptor (IP) activation on spinal
      neurons were investigated with biochemical assays (cyclic adenosine monophosphate
      , glutamate release-measurement, Western blot analysis) in embryonic cultures and
      adult spinal cord. The specific IP antagonist Cay10441 was applied intrathecally
      after zymosan-induced mechanical hyperalgesia in vivo. RESULTS: Peripheral
      inflammation caused a significant increase of the stable PGI2 metabolite 6-keto
      PGF1alpha in the dorsal horn of wild-type mice (n = 5). IP was located on spinal
      neurons and did not colocalize with the prostaglandin E2 receptors EP2 or EP4.
      The selective IP-agonist cicaprost increased cyclic adenosine monophosphate
      synthesis in spinal cultures from wild-type but not from IP-deficient mice (n = 5
      10). The combination of fluorescence-resonance-energy transfer-based cyclic
      adenosine monophosphate imaging and calcium imaging showed a cicaprost-induced
      cyclic adenosine monophosphate synthesis in spinal cord neurons (n = 5-6).
      Fittingly, IP activation increased glutamate release from acute spinal cord
      sections of adult mice (n = 13-58). Cicaprost, but not agonists for EP2 and EP4,
      induced protein kinase A-dependent phosphorylation of the GluR1 subunit and its
      translocation to the membrane. Accordingly, intrathecal administration of the IP
      receptor antagonist Cay10441 had an antinociceptive effect (n = 8-11).
      CONCLUSION: Spinal prostacyclin synthesis during early inflammation causes the
      recruitment of GluR1 receptors to membrane fractions, thereby augmenting the
      onset of central sensitization.

PMID- 23969561
TI  - Simultaneous electroencephalographic and functional magnetic resonance imaging
      indicate impaired cortical top-down processing in association with anesthetic
      induced unconsciousness.
AB  - BACKGROUND: In imaging functional connectivity (FC) analyses of the resting
      brain, alterations of FC during unconsciousness have been reported. These results
      are in accordance with recent electroencephalographic studies observing impaired
      top-down processing during anesthesia. In this study, simultaneous records of
      functional magnetic resonance imaging (fMRI) and electroencephalogram were
      performed to investigate the causality of neural mechanisms during propofol
      induced loss of consciousness by correlating FC in fMRI and directional
      connectivity (DC) in electroencephalogram. METHODS: Resting-state 63-channel
      electroencephalogram and blood oxygen level-dependent 3-Tesla fMRI of 15 healthy
      subjects were simultaneously registered during consciousness and propofol-induced
      loss of consciousness. To indicate DC, electroencephalographic symbolic transfer
      entropy was applied as a nonlinear measure of mutual interdependencies between
      underlying physiological processes. The relationship between FC of resting-state
      networks of the brain (z values) and DC was analyzed by a partial correlation.
      RESULTS: Independent component analyses of resting-state fMRI showed decreased FC
      in frontoparietal default networks during unconsciousness, whereas FC in primary
      sensory networks increased. DC indicated a decline in frontal-parietal (area
      under the receiver characteristic curve, 0.92; 95% CI, 0.68-1.00) and
      frontooccipital (0.82; 0.53-1.00) feedback DC (P<0.05 corrected). The changes of
      FC in the anterior default network correlated with the changes of DC in frontal
      parietal (rpartial=+0.62; P=0.030) and frontal-occipital (+0.63; 0.048)
      electroencephalographic electrodes (P<0.05 corrected). CONCLUSION: The
      simultaneous propofol-induced suppression of frontal feedback connectivity in the
      electroencephalogram and of frontoparietal FC in the fMRI indicates a fundamental
      role of top-down processing for consciousness.

PMID- 23969562
TI  - Medial septal cholinergic neurons modulate isoflurane anesthesia.
AB  - BACKGROUND: Cholinergic drugs are known to modulate the response of general
      anesthesia. However, the sensitivity of isoflurane or other volatile anesthetics
      after selective lesion of septal cholinergic neurons that project to the
      hippocampus is not known. METHODS: Male Long Evans rats had 192 immunoglobulin G
      saporin infused into the medial septum (n = 10), in order to selectively lesion
      cholinergic neurons, whereas control, sham-lesioned rats were infused with saline
      (n = 12). Two weeks after septal infusion, the hypnotic properties of isoflurane
      and ketamine were measured using a behavioral endpoint of loss of righting reflex
      (LORR). Septal lesion was assessed by counting choline acetyltransferase
      immunoreactive cells and parvalbumin-immunoreactive cells. RESULTS: Rats with 192
      immunoglobulin G-saporin lesion, as compared with control rats with sham lesion,
      showed a 85% decrease in choline acetyltransferase-immunoreactive, but not
      parvalbumin-immunoreactive, neurons in the medial septal area. Lesioned as
      compared with control rats showed increased isoflurane sensitivity, characterized
      by a leftward shift of the graph plotting cumulative LORR percent with isoflurane
      dose. However, lesioned and control rats were not different in their LORR
      sensitivity to ketamine. When administered with 1.375% isoflurane, LORR induction
      time was shorter, whereas emergence time was longer, in lesioned as compared with
      control rats. Hippocampal 62-100 Hz gamma power in the electroencephalogram
      decreased with isoflurane dose, with a decrease that was greater in lesioned (n =
      5) than control rats (n = 5). CONCLUSIONS: These findings suggest a role of the
      septal cholinergic neurons in modulating the sensitivity to isoflurane
      anesthesia, which affects both induction and emergence. The sensitivity of
      hippocampal gamma power to isoflurane appears to indicate anesthesia (LORR)
      sensitivity.

PMID- 23969563
TI  - Muscle-tendon lengths according to sagittal knee kinematics in patients with
      cerebral palsy: differences between recurvatum and crouch knee.
AB  - This study evaluated the differences in muscle-tendon lengths during single limb
      support between recurvatum and crouch knee in patients with cerebral palsy. Group
      I consisted of 14 patients who had recurvatum knee, whereas group II consisted of
      17 patients who had crouch knee. Compared with group II, group I had decreased
      ankle power and plantarflexion moment and only the average muscle-tendon lengths
      of the gluteus medius and vasti was decreased. There were no differences in other
      muscle-tendon lengths. Recurvatum and crouch knee could occur with similar muscle
      tendon lengths of the gastrocnemius, semimembranosus, biceps femoris, and rectus
      femoris. 

PMID- 23969564
TI  - Slipped capital femoral epiphysis caused by neurogenic heterotopic ossification.
AB  - Slipped capital femoral epiphysis (SCFE) is rare in nonambulatory patients, as
      mechanical factors play important roles in the development of the disease. We
      report a case of SCFE, which occurred in a 12-year-old girl with a nonambulatory
      status after cerebral infarction. SCFE occurred after she received passive range
      of motion exercise and extracorporeal shock wave treatment for neurogenic
      heterotopic ossification around the hip joint. The patient was successfully
      managed by a stepwise approach, with radiological and clinical improvements. 

PMID- 23969565
TI  - N-heterocyclic carbene catalyzed regioselective oxo-acyloxylation of alkenes with
      aromatic aldehydes: a high yield synthesis of alpha-acyloxy ketones and esters.
AB  - An N-heterocyclic carbene (NHC)-catalyzed reaction of alkenes with aromatic
      aldehydes providing for a high yield synthesis of alpha-acyloxy ketones and
      esters has been described. This unprecedented regioselective oxidative process
      employs NBS and Et3N in stoichiometric amounts and O2 (1 atm) as an oxidant under
      ambient conditions in DMSO as a solvent. 

PMID- 23969566
TI  - Hetero Bodipy-dimers as heavy atom-free triplet photosensitizers showing a long
      lived triplet excited state for triplet-triplet annihilation upconversion.
AB  - Bodipy dimers in which the two different sub-units take an orthogonal orientation
      were prepared, which show strong absorption of visible light, long-lived triplet
      excited states (140.9 MUs) and high singlet oxygen ((1)O2) quantum yields (64%).
      The dimers were used for triplet-triplet annihilation upconversion (quantum yield
      is up to 3.7%). 

PMID- 23969567
TI  - Hospital reputation and perceptions of patient safety.
AB  - OBJECTIVE: The objective of this study was to explore the theoretical
      relationship between the social reputation and the perceived safety of a
      hospital. SUBJECTS AND METHODS: A random sample of 316 patients and 27 relatives
      of patients who were unable to respond themselves at four public hospitals in
      Madrid, Barcelona and Alicante were interviewed to establish a measure of
      reputation and perceived safety. RESULTS: There were no different perceptions
      between patients and relatives regarding hospital reputation or safety perception
      (p > 0.05). The perception of patients or relatives of health professionals'
      competence (beta = 0.07, 95% CI 0.01-0.12), the perception of a positive
      treatment output of surgical or medical treatment (beta = 0.35, 95% CI 0.22-0.49)
      and hospital reputation (beta = 0.08, 95% CI 0.02-0.14) were directly and
      positively associated with their perception that the hospital was a safe clinical
      environment in which few clinical errors are committed. CONCLUSIONS: The data
      suggested that the social reputation of these hospitals and the perceptions of
      patients or relatives of patient safety were indeed correlated. Future research
      should assess whether efforts to enhance hospital reputation, by improving
      patients' perceptions of clinical safety, may contribute to reducing the
      frequency of litigation cases.

PMID- 23969568
TI  - Intravitreal bevacizumab for choroidal neovascularization in age-related macular
      degeneration.
AB  - Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, is
      used in the treatment of cancer. It was the first clinically available
      angiogenesis inhibitor in the U.S. Recently, bevacizumab has been used by
      ophthalmologists in the intravitreal treatment of choroidal neovascularization in
      age-related macular degeneration. Since all published trials were less than one
      year in duration, including follow up, no conclusion can be drawn about the long
      term safety and efficacy of intravitreal bevacizumab. In open-label studies,
      however, intravitreal bevacizumab has yielded marked improvements in visual
      acuity and central retinal thickness. Compounding pharmacists who are validated
      in aseptic compounding can prepare intravitreal bevacizumab from the available
      preservative-free phosphate-buffered intravenous solution using strict aseptic
      technique. 

PMID- 23969569
TI  - Cancer-related terminology: glossaries for compounded pharmacists and their
      clients.
AB  - Webster's dictionary defines cancer as a "pernicious, spreading evil...", a
      definition that is hard to debate. Cancer is a life-changing disease for both the
      patient with cancer and the family members. Compounding pharmacists have the
      resources to assist patients in reducing their pain, nausea, and other symptoms
      of cancer and the side effects of their cancer treatments. By providing a
      glossary of terms for clients affected by cancer, compounding pharmacists also
      can reduce at least a small part of their frustration. The International Journal
      of Pharmaceutical Compounding, Inc., has published many formulations and articles
      dealing with cancer-related symptoms and treatment side effects, and is working
      hard to get more formulations online so we can participate in the challenge and
      victory of defeating the pain and suffering of patients with cancer. 

PMID- 23969570
TI  - Hospice and compounding pharmacy: once inseparable.
AB  - Like hospice, compounding pharmacy offers a specialized service. Hospice
      continues to offer the strong emotional, psychological, and spiritual support to
      dying phatients and their family members that it has provided for many years, but
      the procedure for ordering drugs for the patients of hospice care in the U.S. has
      changed. Most hospice organizations work on a contract-only basis with service
      providers, which include compounding pharmacists, and in most cases a patient's
      drugs are ordered from large, remote pharmaceutical suppliers with whom hospice
      has contracts. At times, hospice patients' medication needs are not met by this
      system, and compounding pharmacists may be called upon in such situations, often
      to assist in the rapid relief of a patient's pain and discomfort. Since not every
      manufactured drug or dosage form is suitable for every patient, especially those
      that have become frail and weak, a compounding pharmacist should be one of the
      most vital members of the hospice team. Unfortunately, from hospice care's humble
      beginning at a time when "compounding" was the sole source of medication, many
      hospice organizations now consider compounding pharmacists and compounded
      preparations as only one of many options for emergency treatments. A once strong
      union is no longer so solid. 

PMID- 23969571
TI  - Disposing of expired drugs and chemicals: new options for compounders.
AB  - Years ago, pharmacists disposed of expired drugs and chemicals by incinerating
      them, flushing them down the toilet, washing them down the sink, or attempting to
      return them to the manufacturer. Some of those methods of disposal have proven
      over time to exert a devastating effect on the environment (and often on the
      local community), and compliance with state and federal regulations for the
      management of expired drugs has become essential to avoid incurring fines and to
      protect the public welfare. Now, pharmacists who must navigate the complexities
      of that effort have professional allies. Over the last decade, the disposal of
      hazardous pharmaceutical waste has become a science, and companies with expertise
      in that specialty are increasing in number. In this article, information about
      several pharmaceutical waste disposal or returns companies is compared, and
      criteria for selecting a drug disposal service are presented. 

PMID- 23969572
TI  - Stability Versus Potency Testing: The Madness is in the Method.
AB  - Potency tests, known as quantitative tests, are designed to determine how much of
      the active drug is in the sample. Stability tests are used to determine a beyond
      use date for a preparation. Employing the proper method to determine potency or
      stability is key to understanding the difference between potency testing and
      stability testing. Methods of determining potency may or may not be stability
      indicating, but stability can be determined only by a stability-indicating
      method. A stability-indicating method can determine both potency and stability.
      Quality assurance programs are essential to establishing standards for compounded
      preparations. It is important that compounding pharmacists understand the
      differences between potency and stability tests and that these tests are made an
      integral part of the quality asurance program. 

PMID- 23969573
TI  - Considerations for implementing United States pharmacopeia chapter 797
      pharmaceutical compounding-sterile preparations, part 5: verification of
      accuracy, sterility, and sterilization of compounded preparations.
AB  - United States Pharmacopeia Chapter 797 Pharmaceutical Compounding-Sterile
      Preparations pertains to all preadministration manipulations and procedures
      involved in the preparation of sterile compounds for application, implantation,
      infusion, inhalation, injection, insertion, instillation, or irrigation,
      including preparation, storage, and transportation. The chapter does not pertain
      to actual clinical administation of compounded sterile preparations to patients.
      The intent of Chapter 797 is simply to prevent patient harm and fatalitites that
      may result from nosterility, excessive endotoxin load, large content errors in
      strength of correct ingredients, or the presence of incorrect ingredients.
      Because the achievement of sterility requires that facilities meet minimum
      cleanliness standards, that personnel be trained adequately and undergo periodic
      testing and training in sterilization techniques, and that appropriate principles
      and practices be applied to sustain solution stablity, compliance with Chapter
      797 should be the goal of any facility where sterile preparations are compounded.
      Many pharmacies have already achieved compliance with Chapter 797, and those that
      have already met the new standards seem to support them strongly. This article
      discusses procedures for verification of the accuracy, sterility, and
      sterilization of compounded preparations. The importance of United States
      Pharmacopeia Chapter 71, 1035, and 1211, all of which contain vital information,
      is also discussed. 

PMID- 23969574
TI  - Specialty compounding for improved patient care: 2006 national survey of
      compounding pharmacists.
AB  - Pharmacy compounding is re-emerging as a critical area of pharmacy practice. This
      re-emergence has generated considerable discussion among stakeholders of the
      pharmacy profession about how pharmacy compounding is best regulated to ensure
      the safety and efficacy of compounded preparations. In light of this discussion,
      the American College of Apothecaries conducted a survey in August 2006 that was
      sent to compounding pharmacists, the list of which was provided by the
      International Journal of Pharmaceutical Compounding. The purpose of the survey
      was to (1)assess the safety and efficacy of compounded preparations as reported
      by compounding pharmacists, (2)describe the types of compounding and other
      professional services that are offered by these pharmacists, (3)describe selected
      business information for compounding pharmacies, and (4)monitor changes in the
      compounding pharmacy landscape since the 2005 National Survey of Compounding
      Pharmacists, the results of which were published in the November/December 2006
      issue of the International Journal of Pharmaceutical Compounding. State boards of
      pharmacy were surveyed for reports of problems related to instability of
      compounded preparations and adverse reactions caused by compounded preparations.
      Data trends in this study are similar to those reported in the 2005 survey, also
      conducted by the American College of Apothecaries. Repsondents reported
      relatively few adverse events caused by compounded preparations. These
      respondents, many of whom are independent pharmacists, offer a variety of
      compounding, professional, and patient care services. Of 18 responding state
      boards of pharmacy, four noted reports of compounding problems in their state. 

PMID- 23969575
TI  - Room temperature stability of injectable succinylcholine dichloride.
AB  - The purpose of this study was to determine the room temperature stability over a
      period of several months of commercially available intravenous succinylcholine
      dichloride (Quelicin, 20 mg/mL) in vials. A previously validated electro-spray
      tandem mass spectrometry method developed for the determination of
      succinylcholine dichloride in plasma was used. This method was based upon a
      stable isotope dilution assay using hexadeuterosuccinylcholine diiodide as the
      internal standard and was shown to be specific, sensitive, and reproducible.
      Calibration curves were plots of the ratios of intensities of the major product
      ions in the collision-induced dissociation spectrum for known concentration
      ratios of succinylcholine dichloride and hexadeuterosuccinylcholine diiodide in
      solutions. The concentration of succinylcholine dichloride was shown to decline
      linearly. After 1, 3, and 6 months at room temperature, the vial contents
      retained approximately 98%, 95%, and 90% of their inital concentration,
      respectively. We suggest, therefore, that succinylcholine dichloride can be
      stored safely at room temperature under normal daylight for 6 months. 

PMID- 23969576
TI  - PostScription: Consumer Options for the Disposal of Unused Medications.

PMID- 23969577
TI  - Short-term effect of percutaneous recanalization of chronic total occlusions on
      QT dispersion and heart rate variability parameters.
AB  - BACKGROUND: QT dispersion (QTd), which is a measure of inhomogeneity of
      myocardial repolarization, increases following impaired myocardial perfusion. Its
      prolongation may provide a suitable substrate for life-threatening ventricular
      arrhythmias. We investigated the changes in QTd and heart rate variability (HRV)
      parameters after successful coronary artery revascularization in a patient with
      chronic total occlusions (CTO). MATERIAL/METHODS: This study included 139
      successfully revascularized CTO patients (118 men, 21 women, mean age 58.3+/-9.6
      years). QTd was measured from a 12-lead electrocardiogram and was defined as the
      difference between maximum and minimum QT interval. HRV analyses of all subjects
      were obtained. Frequency domain (LF: HF) and time domain (SDNN, pNN50, and rMSSD)
      parameters were analyzed. QT intervals were also corrected for heart rate using
      Bazett's formula, and the corrected QT interval dispersion (QTcd) was then
      calculated. All measurements were made before and after percutaneous coronary
      intervention (PCI). RESULTS: Both QTd and QTcd showed significant improvement
      following successful revascularization of CTO (55.83+/-14.79 to 38.87+/-11.69;
      p<0.001 and 61.02+/-16.28 to 42.92+/-13.41; p<0.001). The revascularization of
      LAD (n=38), Cx (n=28) and RCA (n=73) resulted in decrease in HRV indices,
      including SDDN, rMSSD, and pNN50, but none of the variables reached statistical
      significance. CONCLUSIONS: Successful revascularization of CTO may result in
      improvement in regional heterogeneity of myocardial repolarization, evidenced as
      decreased QTcd after the PCI. The revascularization in CTO lesions does not seem
      to have a significant impact on HRV.

PMID- 23969578
TI  - Influence of disease severity on fatigue in patients with Parkinson's disease is
      mainly mediated by symptoms of depression.
AB  - PURPOSE: Fatigue is a frequent non-motor complaint of patients with Parkinson's
      disease (PD). Despite increasing knowledge on fatigue, the factors leading to its
      development are still not recognised. The aim of this investigation was to test,
      using structural equation modelling, the hypothesis that the influence of disease
      severity on fatigue is mediated by symptoms of depression in patients with PD.
      METHOD: The sample consisted of 190 PD patients (93 men, 48.9%, mean age 68.2+/
      9.3 years, mean disease duration 6.4+/-4.7 years) recruited from hospitals and
      outpatient clinics in the East Slovakia region. The Multidimensional Fatigue
      Inventory, the Hospital Anxiety and Depression Scale and the Unified Parkinson's
      Disease Rating Scale were used. LISREL was used to analyse the data. RESULTS:
      Disease severity was directly associated with symptoms of depression (beta=0.26)
      and directly affected fatigue in terms of increased levels of general fatigue
      (beta=0.35), physical fatigue (beta=0.22), reduced activity (beta=0.31) and
      mental fatigue (beta=0.29), but did not directly influence reduced motivation.
      Symptoms of depression mediated the impact of disease severity on general fatigue
      (beta=0.25), on reduced activity (beta=0.31) and on mental fatigue (beta=0.28),
      but not on physical fatigue. Reduced motivation was not mediated, but directly
      influenced by more symptoms of depression (beta=0.82). DISCUSSION: Since
      increased symptoms of depression mediate the impact of disease severity on three
      domains of fatigue in PD patients, disease management should focus on the
      treatment of PD and symptoms of depression.

PMID- 23969579
TI  - Euphol arrests breast cancer cells at the G1 phase through the modulation of
      cyclin D1, p21 and p27 expression.
AB  - Euphorbia tirucalli is a long-established treatment for a wide variety of
      cancers. However, the mechanism of its anticancer effect is yet to be elucidated.
      In the present study, we examined the anticancer effect of euphol, a tetracyclic
      triterpene alcohol isolated from the sap of Euphorbia tirucalli, in T47D human
      breast cancer cells. Following the treatment of cells with different doses of
      euphol for 24, 48 and 72 h, the cell proliferation, cell cycle, and mRNA and
      protein levels of cell cycle regulatory molecules were analyzed, respectively.
      Treatment of the cells with euphol resulted in decreased cell viability, which
      was accompanied by an accumulation of cells in the G1 phase. Further studies
      demonstrated that euphol treatment downregulated cyclin D1 expression and the
      hypophosphorylation of Rb. Furthermore, this effect was correlated with the
      downregulation of cyclin-dependent kinase 2 (CDK2) expression and the
      upregulation of the CDK inhibitors p21 and p27. Reduced expression levels of
      cyclin A and B1 were also observed, corresponding to the decreased distribution
      of cells in the S and G2/M phases, respectively. These findings indicated that
      euphol is an active agent in Euphorbia tirucalli that exerts anticancer activity
      by arresting the cell cycle of cancer cells.

PMID- 23969580
TI  - Unusual presentations of type 2 idiopathic macular telangiectasia.
AB  - PURPOSE: To report unusual presentations of type 2A idiopathic macular
      telangiectasia (IMT). METHODS: A retrospective analysis of disease presentation
      was conducted in 32 patients with type 2A IMT. All patients underwent a complete
      ophthalmological examination, including spectral domain optical coherence
      tomography (SD-OCT), fluorescein angiography (FA) and indocyanine green
      angiography (ICGA). RESULTS: Three out of 32 study patients showed the
      simultaneous presentation of type 2 IMT and other retinal diseases. In the first
      patient, the ophthalmological examination revealed a proliferative IMT associated
      with late-onset Stargardt disease. The second patient presented bilateral
      nonproliferative IMT and chronic serous chorioretinopathy in the left eye. The
      examination of the third patient revealed basal laminar drusen and soft drusen
      associated with IMT in both eyes. CONCLUSIONS: Type 2 IMT may represent an
      unusual presentation of Stargardt disease, chronic serous chorioretinopathy and
      basal laminar drusen. These presentations are most likely coincidental and
      highlight the importance of FA, ICGA and SD-OCT in the diagnosis and treatment of
      such cases.

PMID- 23969581
TI  - A novel prehospital electrocardiogram score predicts myocardial salvage in
      patients with ST-segment elevation myocardial infarction evaluated by cardiac
      magnetic resonance.
AB  - OBJECTIVES: We hypothesized that prehopsital ECG scores can identify ST-segment
      elevation myocardial infarction (STEMI) patients in whom time delay is
      particularly important for myocardial salvage. METHODS: We evaluated the Anderson
      Wilkins (AW) score (which designates the acuteness of ischemia) and grade 3
      ischemia (GI3) (which identifies severe ischemia) in the prehospital ECG and
      compared them to the myocardial salvage index (MSI) assessed by cardiac magnetic
      resonance. RESULTS: In 150 patients, system delay (alarm to balloon inflation)
      (beta = -0.304, p < 0.001) and AW score (beta = 0.364, p < 0.001) correlated with
      MSI. AW scores >=3 (p < 0.001) and GI3 (p = 0.002) predicted the MSI. We formed 4
      subgroups combining AW scores (<3 or >=3) and grades of ischemia (<GI3 or =GI3),
      yielding a prehospital salvage score of 1-4, which predicted the MSI (p < 0.001),
      left ventricular ejection fraction at 3 months (p = 0.017), infarct size (p <
      0.001), and troponin T (p < 0.001). MSI was only dependent on system delay in
      patients with acute ischemia (AW score = 3) with (beta = -0.687, p = 0.005) or
      without (beta = -0.454, p < 0.001) severe ischemia (GI3). CONCLUSION: In patients
      with STEMI, the novel prehospital salvage score identifies subgroups in which
      myocardial salvage is particularly time dependent.

PMID- 23969582
TI  - Annual rescreening for alcohol misuse: diminishing returns for some patient
      subgroups.
AB  - BACKGROUND: Routine alcohol screening is widely recommended, and Medicare now
      reimburses for annual alcohol screening. Although up to 18% of patients will
      screen positive for alcohol misuse, the value of annual rescreening for patients
      who repeatedly screen negative is unknown. OBJECTIVE: To evaluate the probability
      of converting to a positive alcohol screen at annual rescreening among VA
      outpatients who previously screened negative 2-4 times. RESEARCH DESIGN:
      Retrospective cohort study. SUBJECTS: A total of 179,035 VA outpatients (10,588
      women) who previously screened negative on 2 and up to 4 consecutive annual
      alcohol screens and were rescreened the next year. MEASURES: AUDIT-C alcohol
      screening scores (range, 0-12) were obtained from electronic medical record data.
      The probability of converting to a positive screen (scores: men >=4; women, >=3)
      at rescreening after 2-4 prior negative screens was evaluated overall and across
      subgroups based on age, sex, and prior negative screen scores (scores: men, 0-3;
      women, 0-2). RESULTS: The overall probability of converting to a positive
      subsequent screen decreased modestly from 3.5% to 1.9% as the number of prior
      consecutive negative screens increased from 2 to 4, yet varied widely across
      subgroups based on age, sex, and prior negative screen scores (0.6%-38.7%).
      CONCLUSIONS: The likelihood of converting to a positive screen at annual
      rescreening is strongly influenced by age, sex, and scaled screening scores on
      prior negative alcohol screens. Algorithms for the frequency of repeat alcohol
      screening for patients who repeatedly screen negative should be based on these
      factors. These results may have implications for other routine behavioral health
      screenings.

PMID- 23969583
TI  - Do additional recontacts to increase response rate improve physician survey data
      quality?
AB  - BACKGROUND: Although response rates for physician surveys have been decreasing,
      it is not clear whether this trend is associated with an increase in survey
      nonresponse bias. One means for assessing potential bias is to conduct a level-of
      effort analysis that compares data estimates for respondents interviewed during
      the first recruitment contact to respondents interviewed at later recontact
      cycles. METHODS: We compared early and later responders within the Survey of
      Physician Attitudes Regarding the Care of Cancer Survivors with respect to both
      demographic characteristics and aggregate survey responses to items on survivor
      care knowledge, attitudes, and practices. RESULTS: Accumulating additional
      completions across each of 4 respondent contact attempts improved weighted
      response rates (35.0%, 46.9%, 52.3%, and 57.6%, respectively). However, the
      majority of estimates for analyzed variables remained relatively unchanged over
      additional cycles of recontact. CONCLUSIONS: We conclude that additional
      respondent recontact attempts, especially beyond a single recontact, had little
      influence on key data distributions, suggesting that these were ineffective in
      reducing nonresponse bias. Further, the conduct of additional recruitment
      recontacts was an inefficient means for increasing statistical power. For the
      conduct of physician surveys, a practice that may in some cases be cost
      effective, while also controlling total survey error, is to establish a larger
      initial sample; to either eliminate nonresponse follow-up or to limit this to one
      recontact; and to accept a somewhat lower final overall survey response rate.

PMID- 23969584
TI  - Hospitalization and skilled nursing care are predictors of influenza vaccination
      among patients on hemodialysis: evidence of confounding by frailty.
AB  - BACKGROUND: Observational studies of preventive medications, such as
      vaccinations, can suffer from the healthy-user bias because vaccinated patients
      may be healthier than unvaccinated patients. Indicators of health status and
      frailty suitable for attenuating this bias could be identified in administrative
      data. OBJECTIVE: To examine the association of baseline variables and time
      dependent hospitalization and skilled nursing care with the receipt of influenza
      vaccination in patients with end-stage renal disease. RESEARCH DESIGN:
      Observational cohort study using United States Renal Data System files each year
      from 1999 to 2005. SUBJECTS: Population-based cohorts that included >115,000
      adult, hemodialysis patients each year. MEASURES: We estimated hazard ratios for
      the association of baseline variables and time-dependent hospitalization days and
      skilled nursing days with influenza vaccination, controlling for demographic and
      baseline health status variables. RESULTS: Vaccination coverage increased from
      47% in 1999 to 60% in 2005. Patients with any length of hospitalization were less
      likely to be vaccinated, however, the association was stronger in patients with
      longer stays [15-25 d: hazard ratio=0.64 (95% confidence interval, 0.62-0.65); 26
      30 d: 0.40 (0.38-0.42)]. Patients with any length of skilled nursing care of >1
      day had similar estimates; these patients were also less likely to be vaccinated
      [26-30 d: 0.66 (0.64-0.69)]. CONCLUSIONS: Patients with long hospitalizations or
      skilled nursing stays were less likely to be vaccinated suggesting evidence of
      the healthy-user effect. These variables could be used to account for bias in
      studies of preventive services in patients on dialysis.

PMID- 23969585
TI  - Variation in inpatient tonsillectomy costs within and between US hospitals
      attributable to postoperative complications.
AB  - BACKGROUND: Tonsillectomy is the second most common inpatient procedure in US
      children. However, the factors that influence tonsillectomy-related costs are
      unknown. OBJECTIVE: The objective of the study was to describe variation in US
      inpatient tonsillectomy costs and examine whether postoperative complications
      contribute to these disparities in costs. RESEARCH DESIGN: This is a
      retrospective cohort study of the 2009 Nationwide Inpatient Sample. Hierarchical,
      mixed-effects linear regression modeling was used to analyze the association
      between postoperative complications and cost, controlling for clinically relevant
      characteristics such as age, number of chronic comorbidity indicators, and
      hospital mean complication rates. We also estimated the variance in cost
      attributable to the treating hospital using the intraclass correlation
      coefficient. SUBJECTS: The study cohort comprised 12,512 adult and pediatric
      patients undergoing tonsillectomy or adenotonsillectomy in the inpatient setting.
      MEASURES: Cost, posttonsillectomy hemorrhage, and mechanical ventilator use at
      the individual encounter and at hospital level were evaluated. RESULTS: The
      aggregate cost of tonsillectomies in the cohort was $94.2 million. The median
      cost per encounter across all hospitals was $4393 (interquartile range, $3279
      $6981), whereas the mean cost was $7525 (95% confidence interval, $6453-$8597).
      Mechanical ventilation was associated with an adjusted increase of $30,081 per
      encounter (95% confidence interval, $18,199-$41,964). The intraclass correlation
      coefficient declined from 0.117 to 0.070 after adjusting for mean hospital
      mechanical ventilation rate, which accounted for 40.2% of the interhospital
      variation in cost. CONCLUSIONS: Use of mechanical ventilation significantly
      increases the cost of inpatient tonsillectomy care. Further research should
      examine risk factors contributing to higher rates of mechanical ventilation after
      tonsillectomy, which in turn can guide systemic quality improvement interventions
      to reduce costs.

PMID- 23969586
TI  - Adequacy of lymph node examination in colorectal surgery: contribution of the
      hospital versus the surgeon.
AB  - BACKGROUND: Examination of at least 12 lymph nodes (LNs) in the staging of colon
      cancer (CC) was recommended by the National Comprehensive Cancer Network in 2000;
      however, rates of an adequate examination remain low. This study compares the
      impact of the hospital contextual variance against that of the operating surgeon
      on delivery of an adequate LN examination. STUDY DESIGN: Retrospective analysis
      of California Cancer Registry data for all CC operations (2001-2006).
      Hierarchical models predicted the adequacy of LN examination as a function of
      patient, surgeon, and hospital characteristics. Models were created using
      penalized quasi-likelihood approximation with second order Taylor linearization
      as implemented in MLwiN 2.15. RESULTS: A total of 25,606 resections involving
      3376 surgeons operating in 346 hospitals were analyzed. Half of cases had an
      adequate examination. Hierarchical models showed the median odds of an adequate
      examination associated with the hospital context [(MORhosp 2.05; 95% confidence
      interval, 1.9-2.2) was much higher than that associated with the surgeon (MORsurg
      1.34; 95% confidence interval, 1.2-1.4)]. Hospital characteristics teaching and
      high volume predicted higher odds of an adequate examination. There was no
      association with hospital revenue. CONCLUSIONS: Approximately half of patients
      undergoing surgery for CC received an adequate LN examination. Hospital
      contextual factors had a stronger association with receipt of an adequate
      examination than surgeon factors. Our results suggest that quality improvement
      initiatives and incentives should be targeted at the hospital level to achieve
      the highest impact. Furthermore, we have identified nonteaching and low volume
      settings as rational targets for these efforts.

PMID- 23969587
TI  - Health care for chronic pain: overuse, underuse, and treatment needs: commentary
      on: chronic pain and health services utilization-is there overuse of diagnostic
      tests and inequalities in nonpharmacologic methods utilization?

PMID- 23969588
TI  - Chronic pain and health services utilization: is there overuse of diagnostic
      tests and inequalities in nonpharmacologic treatment methods utilization?
AB  - BACKGROUND: Few studies have described patterns and determinants of health
      services utilization (HSU) in chronic pain (CP) subjects. We aimed to describe
      these, in particular, regarding medical consultations (MCs), diagnostic tests
      (DTs), pain medicines (PMs) and nonpharmacologic treatment methods (NTM)
      utilization. METHODS: A cross-sectional nationwide study was conducted in a
      representative sample of the Portuguese population. The 5094 participants were
      selected using random digit dialling and were contacted by computer-assisted
      telephone interviews. Questionnaires included the brief pain inventory and pain
      disability index. Estimates were adequately weighted for the population. RESULTS:
      Prevalence of CP and CP with moderate to severe disability was 36.7% and 10.8%,
      respectively. Most CP subjects were being managed/treated by health professionals
      (81%) and had high levels of HSU. More than half of them had used imaging DT in
      the previous 6 months. Main factors associated with HSU were as follows: pain
      related disability, intensity, duration, and depressive symptoms for MC
      utilization; sex, pain-related disability, and duration for PM utilization; and
      education level and depression diagnosis for NTM utilization. CONCLUSIONS: The
      main drivers behind HSU are pain severity, psychological distress, and socio
      economic determinants. An important set of benchmarks are presented regarding HSU
      in CP subjects, comprising useful tools for public health policy and decision
      making. Results presented may suggest possible inequalities in the access to NTM,
      and interventions to improve access are encouraged. Moreover, possible indirect
      evidence of imaging DT overuse is presented, and it is recommended that their use
      in CP subjects should more closely follow existing guidelines.

PMID- 23969590
TI  - Service use at the end-of-life in Medicare advantage versus traditional Medicare.
AB  - BACKGROUND: Relative to traditional fee-for-service Medicare, managed care plans
      caring for Medicare beneficiaries may be better positioned to promote recommended
      services and discourage burdensome procedures with little clinical value at the
      end of life. OBJECTIVE: To compare end-of-life service use for enrollees in
      Medicare Advantage health maintenance organizations (MA-HMO) relative to similar
      individuals enrolled in traditional Medicare (TM). RESEARCH DESIGN, SUBJECTS,
      MEASURES: For a national cohort of Medicare decedents continuously enrolled in MA
      HMOs or TM in their year of death, 2003-2009, we obtained hospice enrollment
      information and individual-level Healthcare Effectiveness Data and Information
      Set utilization measures for MA-HMO decedents for up to 1 year before death. We
      developed comparable claims-based measures for TM decedents matched on age, sex,
      race, and location. RESULTS: Hospice use in the year preceding death was higher
      among MA than TM decedents in 2003 (38% vs. 29%), but the gap narrowed over the
      study period (46% vs. 40% in 2009). Relative to TM, MA decedents had
      significantly lower rates of inpatient admissions (5%-14% lower), inpatient days
      (18%-29% lower), and emergency department visits (42%-54% lower). MA decedents
      initially had lower rates of ambulatory surgery and procedures that converged
      with TM rates by 2009 and had modestly lower rates of physician visits initially
      that surpassed TM rates by 2007. CONCLUSIONS: Relative to comparable TM decedents
      in the same local areas, MA-HMO decedents more frequently enrolled in hospice and
      used fewer inpatient and emergency department services, demonstrating that MA
      plans provide less end-of-life care in hospital settings.

PMID- 23969591
TI  - National antiviral treatment program and the incidence of hepatocellular
      carcinoma and associated mortality in Taiwan: a preliminary report.
AB  - BACKGROUND: Taiwan's Bureau of National Health Insurance launched the National
      Antiviral Treatment Program (NATP) in 2003 to reimburse patients for antiviral
      drugs and interferons for chronic hepatitis B and C. The objective was to examine
      the impact of the NATP on the incidence and mortality due to hepatocellular
      carcinoma (HCC). METHODS: The cumulative numbers of NATP participants were
      retrieved from the National Health Insurance claims database. The national
      incidence and mortality rates of HCC were obtained from the Taiwan Cancer
      Registry in each quarter from 1979 to 2009. An interrupted time-series analysis
      was applied to test the temporal trend change before and after NATP. RESULTS:
      From 1979 to 1995, the HCC incidence increased in men and women of all age
      groups. From 2003 to 2009, 31,155 men and 10,769 women received anti-hepatitis B
      virus therapy, whereas 13,939 men and 10,721 women received anti-hepatitis C
      virus therapy. The incidence of HCC reached a plateau and then started to decline
      in men aged 30-39 (slope change P=0.003), 50-59 (P=0.051), and 60-69 years
      (P<0.001). A similar trend was noted in women aged 50-59 (P=0.035), 60-69
      (P=0.006), and 70-79 years (P=0.052). The HCC mortality rate had been decreasing
      since 1996 and a further decline was observed after 2004 in men aged 60-69 years
      and women aged 60-79 years. CONCLUSIONS: There is a strong temporal relationship
      between NATP and the stabilization of the HCC incidence and related mortality.
      The cost-effectiveness of the NATP needs further evaluation.

PMID- 23969589
TI  - Reasons for not prescribing guideline-recommended medications to adults with
      heart failure.
AB  - BACKGROUND: Little is known about how often contextual factors such as patient
      preferences and competing priorities impact prescribing of guideline-recommended
      medications, or about the extent to which these factors are documented in medical
      records and available to performance measurement systems. METHODS: Mixed-methods
      study of 295 veterans aged 50 years and older in 4 VA health care systems who had
      systolic heart failure and were not prescribed a beta-blocker and/or an
      angiotensin converting enzyme inhibitor or angiotensin-receptor blocker. Reasons
      for nontreatment were identified from clinic notes and from interviews with 62
      primary care clinicians caring for these patients. These reasons were classified
      using a published taxonomy. RESULTS: Among 295 patients not receiving guideline
      recommended drugs for heart failure, chart review identified biomedical reasons
      for nonprescribing in 42%-58% of patients and contextual reasons in 11%-17%.
      Clinician interviews identified twice as many reasons for nonprescribing as chart
      review (mean 1.6 vs. 0.8 reasons per patient, P<0.001). In these interviews,
      biomedical reasons for nonprescribing were cited in 50%-70% of patients, and
      contextual reasons in 64%-70%. The most common contextual reasons were
      comanagement with other clinicians (32%-35% of patients), patient preferences and
      nonadherence (15%-24%), and clinician belief that the medication is not indicated
      in the patient (12%-20%). CONCLUSIONS: Contextual reasons for not prescribing
      angiotensin converting enzyme inhibitor / angiotensin-receptor blockers and beta
      blockers are present in two thirds of patients with heart failure who did not
      receive these medications, yet are poorly documented in medical records. The
      structure of medical records should be improved to facilitate documentation of
      contextual reasons for not providing guideline-recommended care.

PMID- 23969592
TI  - Out of context: clinical practice guidelines and patients with multiple chronic
      conditions: a systematic review.
AB  - BACKGROUND: Poor fidelity to practice guidelines in the care of people with
      multiple chronic conditions (MCC) may result from patients and clinicians
      struggling to apply recommendations that do not consider the interplay of MCC,
      socio-personal context, and patient preferences. OBJECTIVE: The objective of the
      study was to assess the quality of guideline development and the extent to which
      guidelines take into account 3 important factors: the impact of MCC, patients'
      socio-personal contexts, and patients' personal values and preferences. RESEARCH
      DESIGN: We conducted a systematic search of clinical practice guidelines for
      patients with type 2 diabetes mellitus published between 2006 and 2012. Ovid
      Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE,
      Scopus, EBSCO CINAHL, and the National Guideline Clearinghouse were searched. Two
      reviewers working independently selected studies, extracted data, and evaluated
      the quality of the guidelines. RESULTS: We found 28 eligible guidelines, which,
      on average, had major methodological limitations (AGREE II mean score 3.8 of 7,
      SD=1.6). Patients or methodologists were not included in the guideline
      development process in 20 (71%) and 24 (86%) guidelines, respectively. There was
      a complete absence of incorporating the impact of MCC, socio-personal context,
      and patient preferences in 8 (29%), 11 (39%), and 16 (57%) of the 28 guidelines,
      respectively. When mentioned, MCC were considered biologically, but not as
      contributors of complexity or patient work or as motivation to focus on patient
      centered outcomes. CONCLUSIONS: Extant clinical practice guidelines for one
      chronic disease sometimes consider the context of the patient with that disease,
      but only do so narrowly. Guideline panels must remove their contextual blinders
      if they want to practically guide the care of patients with MCC.

PMID- 23969594
TI  - Medicare Part D is associated with reducing the financial burden of health care
      services in Medicare beneficiaries with diagnosed diabetes.
AB  - BACKGROUND: Medicare Part D, implemented in 2006, provided coverage for
      prescription drugs to all Medicare beneficiaries. OBJECTIVE: To examine the
      effect of Part D on the financial burden of persons with diagnosed diabetes.
      RESEARCH DESIGN, SUBJECTS, AND OUTCOME MEASURES: We conducted an interrupted time
      series analysis using data from the 1996 to 2008 Medical Expenditure Panel Survey
      (11,178 persons with diabetes who were covered by Medicare, and 8953 persons aged
      45-64 y with diabetes who were not eligible for Medicare coverage). We then
      compared changes in 4 outcomes: (1) annual individual out-of-pocket expenditure
      (OOPE) for prescription drugs; (2) annual individual total OOPE for all health
      care services; (3) annual total family OOPE for all health care services; and (4)
      percentage of persons with high family financial burden (OOPE >=10% of income).
      RESULTS: For Medicare beneficiaries with diabetes, Part D was associated with a
      28% ($530) decrease in individual annual OOPE for prescription drugs, a 23%
      ($560) reduction in individual OOPE for all health care, a 23% ($863) reduction
      in family OOPE for all health care, and a 24% reduction in the percentage of
      families with high financial burden in 2006. There were similar reductions in
      2007 and 2008. By 2008, the percentage of Medicare beneficiaries with diabetes
      living in high financial burden families was 37% lower than it would have been
      had Part D not been in place. CONCLUSIONS: Introduction of Part D coverage was
      associated with a substantial reduction in the financial burden of Medicare
      beneficiaries with diabetes and their families.

PMID- 23969593
TI  - Measuring symptoms in community-dwelling older adults: the psychometric
      properties of a brief symptom screen.
AB  - BACKGROUND: With aging, the probability of experiencing multiple chronic
      conditions has increased, along with symptoms associated with these conditions.
      Symptoms form a central component of illness burden, and distress. To date, most
      symptom measures have focused on a particular disease population. OBJECTIVE: We
      aimed to develop and evaluate a simple symptom screen using data obtained from a
      representative sample of community-dwelling older adults. METHODS: Psychometric
      analyses were conducted on 10 self-reported dichotomous symptom indicators
      collected during in-person interviews from a sample of 1000 community-dwelling
      older adults. Symptoms included shortness of breath, feeling tired or fatigued,
      problems with balance or dizziness, perceived weakness in legs, constipation,
      daily pain, stiffness, poor appetite, anxiety, and anhedonia. RESULTS: Over one
      third of the individuals (37.4%) had 5 or more concurrent symptoms. Stiffness and
      feeling tired were the most common symptoms. Confirmatory factor analyses were
      performed on the 10 symptoms for single factor and bifactor (physical and
      affective) models of symptom reporting. Goodness-of-fit indices indicated better
      fit for the bifactor model (chidf=10=89.6; P<0.001), but the practical
      significance of the improvement in fit was negligible. Differential item
      functioning analyses showed some differences of relatively high magnitude in
      location parameters by race; however, because the differential item functioning
      was in different directions, the impact on the overall measure was most likely
      lessened. CONCLUSIONS: Among community-dwelling older adults, a large proportion
      experienced multiple co-occurring symptoms. This Brief Symptom Screen can be used
      to quickly measure the overall symptom load in older adult populations, including
      those with multiple chronic conditions.

PMID- 23969596
TI  - Sensing nanoparticles using a double nanohole optical trap.
AB  - We use a double nanohole (DNH) optical trap to quantify the size and
      concentration of nanoparticles in solution. The time to trap shows a linear
      dependence with nanosphere size and a -2/3 power dependence with nanosphere
      concentration, which is in agreement with simple microfluidic considerations. The
      DNH approach has size-specificity on the order of a few nanometers, which was
      used to selectively quantify particles of a single size within a heterogeneous
      solution. By looking at individual trapping events, it is in principle possible
      to extend this approach to the ultimate limit of a single particle concentration,
      while also being able to operate at high concentrations in the same
      configuration. In addition, the DNH trap allows us to hold onto individual
      particles and thereby study constituents of a heterogeneous mixture. By repeating
      the trapping measurements on spherical particles of different refractive index,
      we found that the transmission step that indicates trapping scales empirically
      with the Clausius-Mossotti factor. This approach may be applied to several
      sensing applications, such as in the study of virus populations, where
      concentrations vary over many orders of magnitude. 

PMID- 23969597
TI  - Tractography-guided stimulation of somatosensory fibers for thalamic pain relief.
AB  - BACKGROUND: The spinothalamocortical tract (STC) is seen as a neural tract
      responsible for or involved in the generation or transmission of thalamic pain.
      Either the thalamus itself or the posterior limb of the internal capsule (PLIC)
      are targets for deep brain stimulation (DBS) in patients with thalamic pain, but
      due to its low contrast, conventional MRI cannot visualize the STC directly.
      OBJECTIVES: To show the feasibility of integrating diffusion tensor imaging-based
      tractography into the stereotactic treatment planning for identification of an
      object-oriented lead trajectory that allows STC-DBS with multiple electrode
      contacts. METHODS: Diffusion tensor imaging was performed in 4 patients with
      thalamic pain. The STC was modeled and integrated into the stereotactic treatment
      planning for DBS. DBS-lead implantation was done according to trajectory planning
      along the modeled STC at the level of the PLIC. RESULTS: After implantation,
      electrode stimulation was possible over a length of more than 20 mm with a
      tractography-based trajectory along the PLIC part of the STC. After a follow-up
      of 12 months, pain relief of more than 40% was achieved in 3 of 4 patients with
      rating on a visual analogue scale. In 1 patient, stimulation failed to reach any
      long-lasting positive effects. CONCLUSIONS: Integrating tractography data into
      stereotactic planning of DBS in thalamic pain is technically feasible. It can be
      used to identify a lead trajectory that allows for multiple contact stimulation
      along the STC at the level of the PLIC. Due to long-lasting positive stimulation
      effect, tractography-guided stimulation of sensory fibers seems to be beneficial
      for thalamic pain relief.

PMID- 23969598
TI  - The Kiss-1/Kiss-1R complex as a negative regulator of cell motility and cancer
      metastasis (Review).
AB  - Metastasis is a complex multistep process that involves the impairment of cell
      cell adhesion in the neoplastic epithelium, invasion into adjacent tissues and
      the dissemination of cancer cells through the lymphatic and haematogenous routes.
      The inhibition of the metastatic process at an early stage has become a hot topic
      in cancer research. The Kiss-1 gene, initially described as a suppressor of
      metastasis in malignant melanoma, encodes the Kiss-1 protein which can be
      processed to other peptides, e.g., Kisspeptin-10, Kisspeptin-13, Kisspeptin-14
      and Kisspeptin-54. These peptides are endogenous ligands of the Kiss-1 receptor
      (Kiss-1R), a G protein-coupled receptor (GPR) also known as hOT7T175, AXOR12 or
      GPR54. The Kiss-1 gene has been suggested as a suppressor of metastasis in a
      various types of cancer, including gastric cancer, oesophageal carcinoma,
      pancreatic, ovarian, bladder and prostate cancer, through the regulation of
      cellular migration and invasion. In the current review, we summarise the current
      understanding of the role of Kiss-1 and Kiss-1R in cancer and cancer metastasis.

PMID- 23969599
TI  - Hydration and speciation studies of Mn2+ in aqueous solution with simple
      monovalent anions (ClO4-, NO3-, Cl-, Br-).
AB  - Raman spectroscopic measurements have been performed on aqueous solutions of
      Mn(ClO4)2, MnCl2, MnBr2, and Mn(NO3)2 in the terahertz region (40-600 cm(-1)) and
      to wavenumbers up to 4200 cm(-1) employing an absorption gap in these light pink
      coloured solutions. In Mn(ClO4)2 solutions of water and heavy water, the
      hexahydrate and its deuterate, [Mn(OH2)6](2+) and [Mn(OD2)6](2+), were
      characterized as showing a very weak, strongly polarized band at 354 cm(-1) and
      338 cm(-1), respectively. These modes were assigned to nu1 MnO6 of [Mn(OH2)6](2+)
      and [Mn(OD2)6](2+). In Mn(NO3)2(aq), the undisturbed mode at 354 cm(-1),
      representative of manganese hexahydrate, was also detected in dilute solutions up
      to ~3 mol L(-1) and no sign of nitrato complex formation could be obtained. In
      fairly dilute MnCl2(aq) up to ~1.5 mol L(-1) the hexaaqua ions were identified
      but in concentrated solutions, chloro-complexes of Mn(2+) were detected in the
      form of [Mn(OH2)(6-n)Cl(n)]((+2-n)) with n equal to one or two. In MnBr2(aq) a
      comparable picture to the one in MnCl2(aq) could be obtained. Density functional
      theory (DFT) calculations on Mn(2+) water clusters were carried out to optimize
      the geometry and calculate the frequencies of the [Mn(OH2)6](2+) cluster. For
      this purpose an unrestricted B3LYP functional was used with a triple-zeta basis
      set 6-311+G(d,p). In order to include the hydration effects around the
      [Mn(OH2)6](2+), a continuum model approach was employed where the solvent is
      described by a structureless dielectric polarizable continuum using the
      Polarizable Continuum Model of Solvation (PCM). The gas phase cluster of
      [Mn(OH2)6](2+) led to lower MnO6 frequencies compared to the measured ones. A
      second, much larger cluster model, with 18 water molecules containing 6 waters in
      the first shell and an explicit second hydration shell, [Mn(OH2)6(OH2)12](2+),
      was modelled. Again, the cluster in vacuo and the cluster surrounded by a
      structureless polarizable continuum were considered. The larger cluster including
      the polarizable continuum gives the most realistic frequency value of nu1 MnO6
      and the other MnO6 skeleton modes. The hydration enthalpy, DeltaH(hyd(l)) at 298
      K, of [Mn(OH2)6](2+)(aq) was calculated by applying a Born-Haber cycle and
      correcting for the heat of vaporization, DeltaH(vap), of water and the solvation
      enthalpy, DeltaH(solv), released by transferring the gas phase cluster into the
      solution. The theoretical hydration enthalpy is in fair agreement with the
      measured hydration enthalpy.

PMID- 23969601
TI  - CD97 is a multifunctional leukocyte receptor with distinct roles in human cancers
      (Review).
AB  - G-protein coupled receptors (GPCRs) represent the most diverse and biologically
      ubiquitous protein receptors. The epidermal growth factor seven-span
      transmembrane (EGF-TM7) family consists of adhesion GPCRs with a diverse
      functional repertoire. CD97 is the most broadly expressed member with roles in
      cell adhesion, migration and regulation of intercellular junctions. CD97 is also
      expressed in a variety of human malignancies including those of the thyroid,
      stomach, colon and brain. CD97 confers an invasive phenotype and has been shown
      to correlate with tumor grade, lymph node invasion, metastatic spread and overall
      prognosis. More recently, CD97 was found to signal through Galpha12/13, resulting
      in increased RHO-GTP levels. Proven roles in tumor invasion and signaling make
      CD97 an exciting novel therapeutic target. In this review, we will discuss the
      structure and function of this receptor, with a specific focus on its mechanistic
      significance in neoplastic diseases. 

PMID- 23969602
TI  - Current compounding practices in europe.
AB  - Compounding is a worldwide practice that has evolved over centuries. Compounding
      has developed differently throughout the world, however, and today, approaches to
      preparing customized medications vary greatly among countries. This doctoral
      project was undertaken, therefore, to obtain data that highlight the similarities
      and differences in compounding across Europe. In this report, we present our
      preliminary findings regarding compounding in Portugal and the United Kingdom.
      Throughout Europe, there is a need for consensual standards of compounding
      practice and common monographs for preparations, and our ongoing research is
      designed to provide a key contribution to the standardization of compounding
      among European countries. 

PMID- 23969600
TI  - Plastid genome instability leads to reactive oxygen species production and
      plastid-to-nucleus retrograde signaling in Arabidopsis.
AB  - The plastid genome is highly conserved among plant species, suggesting that
      alterations of its structure would have dramatic impacts on plant fitness.
      Nevertheless, little is known about the direct consequences of plastid genome
      instability. Recently, it was reported that the plastid Whirly proteins WHY1 and
      WHY3 and a specialized type-I polymerase, POLIB, act as safeguards against
      plastid genome instability in Arabidopsis (Arabidopsis thaliana). In this study,
      we use ciprofloxacin, an organelle double-strand break-inducing agent, and the
      why1why3polIb-1 variegated mutant to evaluate the impact of generalized plastid
      DNA instability. First, we show that in why1why3polIb-1 and ciprofloxacin-treated
      plants, plastid genome instability is associated with increased reactive oxygen
      species production. Then, using different light regimens, we show that the
      elevated reactive oxygen species production correlates with the appearance of a
      yellow-variegated phenotype in the why1why3polIb-1 population. This redox
      imbalance also correlates to modifications of nuclear gene expression patterns,
      which in turn leads to acclimation to high light. Taken together, these results
      indicate that plastid genome instability induces an oxidative burst that favors,
      through nuclear genetic reprogramming, adaptation to subsequent oxidative
      stresses. 

PMID- 23969603
TI  - Compounding around the world.
AB  - Pharmaceutical compounding is universal in its prevalence. Variations in disease
      patterns, culture, and tradition; the role of government in health care; and the
      availability of essential equipment and required agents shape a compounding
      profile unique to each country worldwide. In the following reflections,
      pharmacists form Argentina, Belgium, Colombia, Germany, Puerto Rico, Spain, and
      the United States describe their experiences in the compounding setting unique to
      their practice and their nation. The unifying theme in their comments is the
      dedication of each contributor to enabling recovery and ensuring the good health
      of his or her clients. 

PMID- 23969604
TI  - Establishing a quality-assurance program for hospital compounding.
AB  - Quality assurance is an ongoing process whereby procedures are reviewed
      constantly and changed if necessary to improve the quality of patient care and
      safety. Since most compounding in hospitals is for off-label uses and is usually
      considered high risk, high volume, or problem prone, close monitoring and
      documentation of compounding activities play vital roles in a quality-assurance
      program. Hospital compounders must be diligent in following all of the standards
      of the United States Pharmacopeia and Joint Commission on Accreditation of
      Healthcare Organizations and the guidelines of the American Society of Health
      System Pharmacists to develop and maintain a good quality-assurance program. All
      compounders should strive to dispense high-quality preparation to provide the
      best patient care. 

PMID- 23969605
TI  - Hormone Therapy: It's Time for a Second Opinion.
AB  - The opinion paper titled "Compounded Bioidentical Hormones," published by the
      American College of Obstetricians and Gynecologists in November 2005, appears to
      be aimed at influencing how some clinicians care for their patients. The paper
      may not accurately report the findings of authors listed in its own references in
      regard to safety and efficacy of bioidentical hormones, nor does it address the
      fact that a number of mass-produced preparations on the market include
      bioidentical estadiol, progesterone, and/or testosterone. The authors of the
      paper take the point of view that hormone therapy does not belong to a class of
      drugs with an indication for individualized dosing, but this position is not
      congruent with the fact that manufacturers of mass-produced hormones have U.S.
      Food and Drug Administration approval when they discuss flexible dosing of
      bioidentical hormones. The opinion paper openly opposes compounded bioidentical
      hormones, yet fails to mention the legal precedence and regulatory oversights
      that support the use of compounded prescriptions to dispense hormone replacement
      therapies, a practice that has since been upheld by a federal court. Also, the
      opinion paper fails to recogninze correlations between plasma and salivary
      hormone levels reported by reserachers listed in its own references. While it is
      always wise for clinicians to review the opinions of medical organizations, it is
      sometimes appropriate to ask for a second opinion. 

PMID- 23969606
TI  - Quality-Control Analytical Methods: Minimizing the Probability of Out-of
      Specification Preparations: Results That Make You Say...Hmmm!
AB  - To prevent compounding of an out-of-specification preparation, the possible
      causes of such an error must be identified and eliminated. Implementation of
      simple practices can decrease the probability of errors, resulting in a safer
      situation for both the patient and the pharmacy. The United States Pharmacopeia
      National Formulary is the standard-setting reference for compounding procedures;
      all compounding pharmacists should read and adhere to those standards. This
      article discusses these standards as they relate to drug potency, sterility,
      endotoxin, and particulate matter results. 

PMID- 23969607
TI  - Basics of compounding: considerations for implementing United States pharmacopeia
      chapter 797 pharmaceutical compounding sterile preparations, part 6: 2008
      revisions to chapter 797.
AB  - United States Pharmacopeia Chapter 797 Pharmaceutical Compounding-Sterile
      Preparations pertains to all preadministration manipulations and procedures
      involved in the preparation of sterile compounds for application, implantation,
      infusion, inhalation, injection, insertion, instillation, or irrigation,
      including preparation, storage and transportation. The chapter does not pertain
      to actual clinical administration of compounded sterile preparations to patients.
      The intent of Chapter 797 is simply to prevent patient harm and fatalities that
      may result from nonsterility , excessive endotoxin load, large content errors in
      strength of correct ingredients, or the presence of incorrect ingredients.
      Because the achievement of sterility requires that facilities meet minimum
      cleanliness standards, that personnel be trained adequately and undergo periodic
      testing and training in sterilization techniques, and that appropriate principles
      and practices be appied to sustain solution stability, compliance with Chapter
      797, and those that have already met the new standards seem to support them
      strongly. A number of significant changes have been made to Chapter 797, and this
      article discusses these changes. 

PMID- 23969608
TI  - Compatibility and stability of palonosetron hydrochloride with four neruomuscular
      blocking agents during simulated y-site administration.
AB  - Palonosetron hydrochloride is a longer-acting selective 5-HT3 receptor antagonist
      that has been approved for the prevention of chemotherapy-induced nausea and
      vomiting and is being evaluated for the prevention of postoperative nausea and
      vomiting. The objective of this study was to evaluate the physical and chemical
      stability of palonosetron hydrochloride 50 mcg/mL when mixed with any of the
      neuromuscular blocking drugs cisatracurium besylate 0.5 mg/mL, rocuronium bromide
      1 mg/mL, succinylcholine chloride 2 mg/mL, and vecuronium bromide 1 mg/mL during
      simulated Y-site administration. Triplicate samples of palonosetron hydrochloride
      with each of the neuromuscular blocking drugs were tested. Samples were stored
      and evaluated for up to 4 hours at room temperature. Physical stability was
      assessed by turbidimetric and particulate measurements and visual inspection.
      Chemical stability was assessed by high-performnace liquid chromatography. All of
      the admixtures were clear and colorless when viewed in normal fluorescent room
      light and when viewed with a Tyndall beam. Measured turbidity and particulate
      content were low initially and remained low throughout the study. The drug
      concentration was unchanged in all of the samples tested. Palonosetron
      hydrochloride is physically and chemically stable with cisatracurium besylate,
      rocuronium bromide, succinylcholine chloride, or vecuronium bromide at the
      concentrations tested during simulated Y-site administration over 4 hours at
      ambient room temperature. 

PMID- 23969609
TI  - Chemical stability of tramadol hydrochloride injection.
AB  - The chemical stability of tramadol hydrochloride injection was studied by using a
      stability-indicating high-performance liquid chromatographic assay method that
      was developed in our laboratory. The concentrations of the drug were related
      directly to peak heights, and the percent relative standard deviation based on
      five injections was 0.9. The products of decomposition and excipients present in
      the dosage form did not interfere with the developed assay method. The injection
      was stable for at least 42 days when stored in clear glass vials at room
      temperature. The pH value of the injection remained constant at 6.7 after 42 days
      of storage, and the physical appearance of the injection did not change during
      the study period. 

PMID- 23969610
TI  - Pharmaceutical development of enteric-release hard gelatin capsules in the
      compounding setting.
AB  - Enteric coated capsules are characterized by their resistance to dissolution in
      low pH environments, such as the stomach, and by their rapid disintegration in a
      higher pH environment, such as the intestine. The surface of hard gelatin
      capsules is usually smooth and nonporous, which limits their coating efficiency.
      We developed a simple, quick, and easily reproducible compounding preparation
      method for enteric-release hard gelatin capsules. Twenty-two batches of 60
      diclofenac sodium capsules each were prepared and then divided into three groups.
      Each group was submitted to a different coating process using a small-scale
      enteric coating machine and a coating process based on the atomization (spraying)
      of organic solutions of polymers. The results of dissolution testing were
      compared statistically within the groups and also with a reference drug control
      (Voltaren DR). Some of the batches in group I and all the batches in groups II
      and III met the pharmacopeial requirements for enteric release, in both acid and
      pH 6.8 phosphate buffer stages. Dissolution of capsules coated with Eudragit L100
      was more efficient than that of other tested systems (P less than 0.05). The
      dissolution assay results for group III in the acid stage were superior to the
      results for the reference drug, but no statistical difference was noticed between
      these two in the phosphate buffer stage. Diclofenac sodium hard gelatin capsules
      coated with cellulose acetate Phthalate or Eudragit L100 presented dissolution
      performance that met pharmacopeial requirements. Furthermore, results obtained
      with Eudragit-coated capsules were comparable to those obtained with the
      reference drug. 

PMID- 23969611
TI  - Compatibility and stability of palonosetron hydrochloride with gentamicin,
      metronidazole, or vancomycin during simulated y-site administration.
AB  - Palonosetron hydrochloride is a relatively long-acting selective 5-HT3 receptor
      antagonist that has been approved for the prevention of chemotherapy-induced
      nausea and vomiting and is being evaluated for the prevention of postoperative
      nausea and vomiting. The objective of this study was to evaluate the physical and
      chemical stability of palonosetron hydrochloride 50 mcg/mL when mixed with
      gentamicin sulfate 5 mg/mL, metronidazole 5 mg/mL, or vancomycin hydrochloride 5
      mg/mL during simulated Y-site administration. Duplicate samples of palonosetron
      hydrochloride with each of the anti-infectives were tested. Samples were stored
      and evaluated for up to 4 hours at room temperature. Physical stability was
      assessed by turbidimetric and particulate measurements and visual inspection.
      Chemical stability was assessed by high-performance liquid chromatography. All of
      the admixtures were clear and colorless when viewed in normal fluorescent room
      light and when viewed with a Tyndall beam. Measured turbidity and particulate
      content were low initially and remained low throughout the study. The drug
      concentration was unchanged in all of the samples tesed. Palonosetron
      hydrochloride is physically and chemically stable with gentamicin sulfate,
      metronidazole, or vancomycin hydrochloride at the concentrations tested during
      simulated Y-site administration over 4 hours at ambient room temperature. 

PMID- 23969612
TI  - PostScription: Accreditation By the Pharmacy Compounding Accreditation Board:
      Raising the Bar for Patient Care.

PMID- 23969613
TI  - Palladium-catalyzed cyclization of bromoenynamides to tricyclic azacycles:
      synthesis of trikentrin-like frameworks.
AB  - Palladium-catalyzed cascade cyclization of bromoenynamides equipped with an
      additional alkyne or ynamide substituent affords azatricyclic products. Using 5-
      to 7-membered ring tethers, this chemistry offers a regiospecific route to highly
      functionalized azacycles. Elaboration to the trikentrin B skeleton is achieved
      from the arylsilane cyclization products. 

PMID- 23969614
TI  - Behavioral effects of clozapine, pimavanserin, and quetiapine in rodent models of
      Parkinson's disease and Parkinson's disease psychosis: evaluation of therapeutic
      ratios.
AB  - No safe, tolerated, and effective treatment for Parkinson's disease psychosis
      (PDP) is available; however, clozapine and quetiapine are often used off-label.
      An ideal PDP drug should have a therapeutic window that alleviates psychotic
      symptoms at doses that allow for maintained motor control and do not cause
      sedation. The present study determined the effective doses of quetiapine,
      clozapine, and the nondopaminergic, selective 5-HT2A inverse agonist/antagonist,
      pimavanserin, in an animal model of PDP and compared them with the doses that
      caused dopamine blockade and sedation. Augmented amphetamine-induced locomotion
      in rats with bilateral substantia nigra lesions was used to assess antipsychotic
      efficacy, whereas blockade of apomorphine-induced rotations in rats with
      unilateral 6-hydroxydopamine lesions was used to assess antidopaminergic action
      and reduction in spontaneous locomotion was used to assess sedation. The
      estimated therapeutic ratios for clozapine and quetiapine varied between 0.81 and
      3.3. In contrast, the estimated therapeutic ratios for pimavanserin were at or
      above 170. These results suggest that a selective 5-HT2A inverse
      agonist/antagonist, such as pimavanserin, may provide distinct advantages
      compared with clozapine or quetiapine as a therapy for PDP. 

PMID- 23969615
TI  - Effects of gabapentin on thermal sensitivity following spinal nerve ligation or
      spinal cord compression.
AB  - Neuropathic pain challenges healthcare professionals and researchers to develop
      new strategies of treatment and experimental models to better understand the
      pathophysiology of this condition. In the present study, the efficacy of
      gabapentin on thermal sensitivity following spinal nerve ligation and spinal cord
      compression was evaluated. The method of behavioral assessment was a well
      validated cortically dependent operant escape task. Spinal nerve ligation
      produced peripheral neuropathic pain whereas spinal cord compression, achieved
      with an expanding polymer placed extradurally, produced a condition of central
      neuropathic pain. Changes in thermal sensitivity were also observed in animals
      undergoing nerve ligation surgery without nerve injury. Gabapentin (50 and 100
      mg/kg) significantly reduced thermal sensitivity to 10 and 44.5  degrees C in
      surgically naive animals as well as those undergoing spinal nerve ligation and
      spinal cord compression. In conclusion, an operant method of behavioral
      assessment was used to show that spinal nerve ligation and spinal cord
      compression produced increases in sensitivity to noxious cold and heat stimuli. A
      decrease in thermal sensitivity was observed following administration of
      gabapentin. The results achieved with these methods are consistent with the
      clinical profile of gabapentin in treating conditions of neuropathic pain.

PMID- 23969616
TI  - Photoinduced charge-transfer dynamics of sequentially aligned donor-acceptor
      systems in an ionic liquid.
AB  - Photoinduced charge separation processes of linear phenyleneethynylene
      derivatives (PEN) with different sequences of electron-withdrawing
      perfluorophenyl groups (A) and electron-donating phenyl groups (D) were
      investigated in an ionic liquid (IL), BmimTFSI, by picosecond time-resolved
      fluorescence (TRF) and transient absorption (TA) spectroscopies. Very rapid
      photoinduced charge separation within 10 ps in AADD was followed by the
      stabilization of the charge-transfer (CT) state by the solvation, while the
      excited states in ADAD and ADDA were ascribable to the locally excited (LE)
      state. Equilibrium between the LE and CT states was established for DAAD with
      time constants of forward and backward processes much faster than the solvation
      time. The relative population of the CT state increases with time owing to the
      dynamic stabilization of the CT state by the solvation. The elementary charge
      separation process, the increase in the CT population, and their relation to the
      solvation time were discussed. 

PMID- 23969617
TI  - An analysis of factors related to recurrence of myxofibrosarcoma.
AB  - OBJECTIVE: Myxofibrosarcoma is clinically characterized by a high frequency of
      local recurrence after surgery. To improve the clinical outcome of patients with
      myxofibrosarcoma, it is imperative to control any postsurgical local recurrence.
      METHODS: In this study, we performed a retrospective clinicopathologic analysis
      of 100 consecutive patients with myxofibrosarcoma to identify factors related to
      poor prognosis. All of the patients had been diagnosed, and had undergone surgery
      at the National Cancer Center Hospital between 1999 and 2008. RESULTS: At the
      initial visit to our hospital, 64 patients had primary myxofibrosarcoma, whereas
      36 had undergone primary unplanned resection at other facilities. Of the 36
      patients, 11 consulted our hospital before recurrence and 25 did so after
      recurrence. A histologically positive margin after surgery was evident in 28% of
      the cases overall. The estimated 5-year recurrence-free survival rate was 74.8%.
      Univariate analysis showed that primary unplanned resection at another facility
      (P = 0.0001) and a histologically positive margin (P = 0.0224) were significant
      predictors of local recurrence. When these two factors were subjected to
      multivariate analysis, only primary unplanned resection at another facility was
      significantly correlated with the estimated recurrence-free survival rate (P =
      0.0011). Primary unplanned resection was also significantly related to the 5-year
      disease-free survival rate (P = 0.0401). CONCLUSIONS: Our findings indicate that
      primary unplanned resection at a non-referral hospital is the most important risk
      factor related to poor prognosis of myxofibrosarcoma. Accurate diagnosis and
      adequate initial surgery are most important factors for improving the clinical
      outcomes of myxofibrosarcoma.

PMID- 23969618
TI  - Tadalafil monotherapy for benign prostatic hyperplasia.

PMID- 23969619
TI  - Evaluating the message or the messenger? Implications for self-validation in
      persuasion.
AB  - Characteristics of persuasive message sources have been extensively studied.
      However, little attention has been paid to situations when people are motivated
      to form an evaluation of the communicator rather than the communicated issue. We
      postulated that these different foci can affect how a source validates message
      related cognitions. Participants focused on the source (Studies 1 and 2) or the
      issue (Study 2) while reading weak or strong message arguments. Later, the
      communicator was described as low or high in credibility. When focused on the
      source, highly motivated participants were more confident and their attitudes
      were more reflective of thoughts when argument quality matched (e.g., weak
      arguments-low credibility) rather than mismatched (e.g., weak arguments-high
      credibility) source credibility. Conversely, when participants were focused on
      the issue, self-validation was greater when credibility was high rather than low
      regardless of argument quality. Implications of these findings for the study and
      practice of persuasion are discussed. 

PMID- 23969620
TI  - The compassion-hostility paradox: the interplay of vigilant, prevention-focused
      self-regulation, compassion, and hostility.
AB  - The present research examined the notion that the prosocial attitude of
      compassion is positively related to the antisocial attitude of hostility given
      that compassion and hostility entail elements reflecting vigilant, prevention
      focused self-regulation. In fact, it was found in four samples (N = 4,903) that
      individuals with a strong vigilant prevention focus reported higher levels on
      measures of hostility as well as higher levels on compassion than individuals
      characterized by a weak prevention focus. In addition, compassion and hostility
      are indeed positively correlated reflecting the Compassion-Hostility Paradox. The
      positive association between compassion and hostility is substantially reduced
      when the chronic level of prevention-focused self-regulation is controlled for. A
      complementary experimental study in which compassion was manipulated revealed an
      effect of compassion on hostility in chronically prevention-focused individuals. 

PMID- 23969621
TI  - Different effects of religion and God on prosociality with the ingroup and
      outgroup.
AB  - Recent studies have found that activating religious cognition by priming
      techniques can enhance prosocial behavior, arguably because religious concepts
      carry prosocial associations. But many of these studies have primed multiple
      concepts simultaneously related to the sacred. We argue here that religion and
      God are distinct concepts that activate distinct associations. In particular, we
      examine the effect of God and religion on prosociality toward the ingroup and
      outgroup. In three studies, we found that religion primes enhanced prosociality
      toward ingroup members, consistent with ingroup affiliation, whereas, God primes
      enhanced prosociality toward outgroup member, consistent with concerns of moral
      impression management. Implications for theory and methodology in religious
      cognition are discussed. 

PMID- 23969622
TI  - Marking time: selective use of temporal landmarks as barriers between current and
      future selves.
AB  - Temporal landmarks such as birthdays and significant calendar dates structure our
      perception of time. People might highlight temporal landmarks spontaneously in an
      effort to regulate connections between temporal selves. Five studies demonstrated
      that landmarks are used spontaneously to induce psychological separation from
      undesirable temporal selves. Participants were more likely to think of events
      that fell in between the current and the future self if an imagined future self
      was negative than if it was positive (Studies 1a, 1b, and 2). Furthermore, when a
      self-enhancement mindset was activated, participants were more likely to call to
      mind intervening temporal landmarks to protect themselves from a negative future
      self than when this mindset was not activated (Study 3). Finally, when
      psychological separations between the current self and a negative future self
      were introduced through alternate means, participants no longer selectively used
      landmarks to separate themselves from this future self (Study 4). 

PMID- 23969623
TI  - Sex differences in succumbing to sexual temptations: a function of impulse or
      control?
AB  - Men succumb to sexual temptations (e.g., infidelity, mate poaching) more than
      women. Explanations for this effect vary; some researchers propose that men and
      women differ in sexual impulse strength, whereas others posit a difference in
      sexual self-control. These studies are the first to test such underlying
      mechanisms. In Study 1, participants reported on their impulses and intentional
      control exertion when they encountered a real-life tempting but forbidden
      potential partner. Study 2 required participants to perform a reaction-time task
      in which they accepted/rejected potential partners, and we used process
      dissociation to separate the effects of impulse and control. In both studies, men
      succumbed to the sexual temptations more than women, and this sex difference
      emerged because men experienced stronger impulses, not because they exerted less
      intentional control. Implications for the integration of evolutionary and self
      regulatory perspectives on sex differences are discussed. 

PMID- 23969624
TI  - One-carbon metabolism and bipolar disorder.
AB  - OBJECTIVE: Folate is one of the most widely used nutraceuticals for the treatment
      of mood disorders. In this article, we review folate metabolism, its relationship
      with bipolar disorder, and its therapeutic potential. METHODS: We searched PubMed
      and the Cochrane Library for relevant articles up to and including the year 2012.
      Background information, proposed mechanisms of action, and results from clinical
      trials were reviewed. RESULTS: Folate is an essential cofactor involved in
      methylation reactions, which are critical for monoamine synthesis and
      homocysteine regulation. Folate level is thought to be associated with mood
      disorders and limited response to antidepressants. Functional deficiency, due to
      a common genetic variant of the methylenetetrahydrofolate reductase (NAD(P)H)
      (MTHFR) gene, could also affect the presentation of bipolar disorder. Sodium
      valproate and lamotrigine, commonly used mood stabilizers for the treatment of
      bipolar disorder, can potentially interfere with folate and homocysteine
      metabolism. Previous studies consistently support the efficacy of folate in the
      treatment of depression; one study showed efficacy in the treatment of mania.
      Biologically active forms of folate formulations, which do not require
      biochemical conversion, could be beneficial in the treatment of bipolar disorder.
      CONCLUSIONS: Folate augmentation could be effective for the treatment of bipolar
      disorder. A common genetic variant of the MTHFR gene might impact the treatment
      effect of folate augmentation. The biologically active form of folate could
      potentially correct mood stabilizer-associated functional folate deficiency, help
      normalize monoamine synthesis, and improve outcomes.

PMID- 23969625
TI  - Do population-wide tobacco control approaches help smokers with mental illness?

PMID- 23969626
TI  - Is too much caution enough?

PMID- 23969627
TI  - Anorexia nervosa and social contagion: clinical implications.

PMID- 23969629
TI  - Ecological factors influencing HIV sexual risk and resilience among young people
      in rural Kenya: implications for prevention.
AB  - Most new HIV infections in Kenya occur among young people. The purpose of this
      study was to understand ecological factors that influence HIV-related sexual risk
      and resilience among young people in rural Kenya and to elicit their ideas for
      HIV prevention interventions. Nine focus groups (N = 199) were conducted with
      both female (55%) and male (45%) participants (ages 14-24 years) living in rural
      communities in Kenya. Findings were organized into thematic areas related to the
      following systems of influence: (i) intrapersonal (substance use, HIV knowledge),
      (ii) interpersonal (peer pressure, lack of parent-child communication,
      interpersonal sexual violence), (iii) institutional/community (pornography,
      transactional sex, 'idleness', lack of role models) and (iv) socio
      cultural/policy (Kikuyu culture, Western influence, religious beliefs, HIV
      related stigma and gendered sexual scripts). Results regarding the types of HIV
      prevention programs that participants believed should be developed for young
      people in rural Kenya revealed seven primary themes, including (i) HIV prevention
      community/group workshops, (ii) condom distribution, (iii) job skills trainings,
      (iv) athletic and social clubs, (v) HIV-related stigma reduction campaigns, (vi)
      community-wide demonstrations and (vii) other HIV/AIDS activities led by young
      people. Implications for the development of culturally and developmentally
      appropriate HIV prevention interventions for young people in rural Kenya are
      discussed. 

PMID- 23969628
TI  - 'It's about the smoke, not the smoker': messages that motivate rural communities
      to support smoke-free policies.
AB  - Rural residents are exposed to sophisticated tobacco advertising and tobacco
      growing represents an economic mainstay in many rural communities. There is a
      need for effective health messages to counter the pro-tobacco culture in these
      communities. To determine relevant cultural themes and key message features that
      affect receptivity to pro-health advertisements among rural residents, 11
      exploratory focus groups and surveys with community advocates (N = 82) in three
      rural Kentucky counties were conducted. Participants reviewed and rated a
      collection of print media advertisements and branding materials used by rural
      communities to promote smoke-free policies. Findings reveal that negative
      emotional tone, loss framing, appeals to religiosity, and shifting focus away
      from smokers are effective strategies with rural audiences. Potential pitfalls
      were identified. Attacks on smokers may not be a useful strategy. Health risk
      messages reinforced beliefs of secondhand smoke harm but some argued that the
      messages needed to appeal to smokers and emphasize health hazards to smokers,
      rather than to non-smokers only. Messages describing ineffectiveness of smoking
      sections were understood but participants felt they were only relevant for
      restaurants and not all public spaces. Emphasis on religiosity and social norms
      shows promise as a culturally sensitive approach to promoting smoke-free
      environments in rural communities. 

PMID- 23969630
TI  - Socio-environmental influences on physical activity among young people: a
      qualitative study.
AB  - This multi-methods qualitative study aimed to identify environmental factors that
      influence physical activity participation among young people in Edinburgh,
      Scotland. School pupils (aged 11-13 years) took part using photography, computer
      blogs, maps and focus group discussions (FGDs). Eleven computer sessions (n =
      131) and 14 FGDs (n = 63) took place. Factors influencing physical activity
      behaviour included proximity and access to local facilities, family and peers and
      the school physical activity environment. A variety of facilitators and barriers
      to participation were also reported. Most notable was the importance of cost and
      value for money when choosing physical activities which, although more evident
      among pupils attending schools in areas of low socio-economic status (SES), was
      relevant across all SES groups. Reporting easy access to sports facilities was
      more common among pupils attending schools from high/medium SES. Use of
      greenspace for physical activity was reported among pupils from all schools, but
      was more common among those from low SES schools. Pupils were, in general,
      satisfied with the facilities available at school, but felt time for physical
      education could be increased. Findings may help inform interventions, aimed at
      promoting physical activity at local level. 

PMID- 23969631
TI  - Spotting and supporting eating disorders in school: recommendations from school
      staff.
AB  - Eating disorders have a high rate of onset in school-aged children. School staff
      are in an excellent position to spot the early warning signs and offer support
      during recovery. This article explores the findings from focus groups conducted
      with 63 members of staff from 29 UK schools with the aims of (i) understanding
      whether they are in a good position to support students with eating disorders and
      (ii) to generate recommendations regarding school staff's training needs for
      spotting and supporting eating disorders. Participants took part in semi
      structured focus groups. These were transcribed and analysed using content
      analysis principles. Five key themes emerged: (i) many staff do not have a basic
      understanding of eating disorders, (ii) eating disorders are taboo in the
      staffroom, (iii) staff do not feel comfortable talking to students about eating
      disorders, (iv) support is needed to ensure the teacher-parent relationship is a
      positive one and (v) school staff would welcome practical ideas for how they can
      best support students during the recovery period. The findings show that school
      staff currently feel ill-equipped to support students with eating disorders and
      endorse a need for focused training for school staff to better enable them to
      support students with eating disorders. 

PMID- 23969632
TI  - Understanding barriers to exercise implementation 5-year post-breast cancer
      diagnosis: a large-scale qualitative study.
AB  - Due to the amount of literature supporting exercise participation after cancer
      diagnosis, there has been recent interest in barriers to exercise engagement
      among cancer patients. However, little is known regarding reasons why people
      choose to disengage and how this disengagement occurs over time. This study aimed
      to qualitatively study the perceived barriers to exercise implementation, 5-year
      post-breast cancer diagnosis. Eighty-three female breast cancer survivors
      participated in a one-to-one semi-structured interview, regarding their
      experience of exercise over the past 5 years following their original
      participation in a group-based structured exercise intervention after diagnosis
      (41 from intervention and 42 from original control group). The data were analysed
      using inductive thematic analysis. The findings included three main themes and
      several subthemes regarding the women's perceived barriers: psychological
      barriers (lack of motivation, fears, dislike of gym, not being the 'sporty
      type'), physical barriers (the ageing process, cancer treatment and other
      physical co-morbidities, fatigue and weight gain) and contextual and
      environmental barriers (employment, traditional female care-giving roles,
      proximity/access to facilities, seasonal weather). The findings add inductive
      support to the current survivor health research advocating the use of activity
      immediately after diagnosis, as well as the need for tailored activity programmes
      in order to overcome potential obstacles.

PMID- 23969633
TI  - Intramuscular pressure before and after botulinum toxin in chronic exertional
      compartment syndrome of the leg: a preliminary study.
AB  - BACKGROUND: Botulinum toxin A (BoNT-A) is used in the treatment of muscle
      hypertrophy but has never been used in chronic exertional compartment syndrome
      (CECS). The objective diagnostic criterion in this condition is an abnormally
      elevated intramuscular pressure (IMP) in the compartment. In this study, the IMP
      was measured 1 minute (P1) and 5 minutes (P5) after the exercise was stopped
      before and after BoNT-A injection. HYPOTHESIS: Botulinum toxin A reduces the IMP
      (P1 and P5) and eliminates the pain associated with CECS. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: Botulinum toxin A was injected into the
      muscles of moderately trained patients with an anterior or anterolateral
      exertional compartment syndrome of the leg. The BoNT-A dose (mean +/- SD) ranged
      from 76 +/- 7 to 108 +/- 10 U per muscle, depending on which of the 5 muscles in
      the 2 compartments were injected. The primary end point was IMP (P1, P5).
      Secondary end points were exertional pain, muscle strength, and safety. Follow-up
      was conducted up to 9 months. RESULTS: A total of 25 anterior compartments and 17
      lateral compartments were injected in 16 patients. The time interval (mean +/-
      SD) between the BoNT-A injection and after BoNT-A injection IMP measurement was
      4.4 +/- 1.6 months (range, 3-9 months). In the anterior compartment, P1 and P5
      fell by 63% +/- 17% (P < .00001) and 59% +/- 24% (P < .0001), respectively; in
      the lateral compartment, P1 and P5 fell by 68% +/- 21% (P < .001) and 63% +/- 21%
      (P < .01), respectively. Exertional pain and muscle strength were monitored,
      based on the Medical Research Council score. The exertional pain was completely
      eliminated in 15 patients (94%). In 5 patients (31%), the strength of the
      injected muscles remained normal. In 11 patients (69%), strength decreased from
      4.5 (out of 5) to 3.5 (P < .01), although without functional consequences. In the
      conditions of this study, BoNT-A showed a good safety profile in patients with
      CECS. CONCLUSION: In this case series, BoNT-A reduced the IMP and eliminated
      exertional pain in anterior or anterolateral CECS of the leg for up to 9 months
      after the intervention. The mode of action of BoNT-A is still unclear. A
      randomized controlled study should be carried out to determine whether BoNT-A can
      be used as a medical alternative to surgical treatment.

PMID- 23969634
TI  - A flavonoid chrysin suppresses hypoxic survival and metastatic growth of mouse
      breast cancer cells.
AB  - Tumor hypoxia commonly occurs in solid tumors, and correlates with metastasis.
      Current cancer therapies are inefficient in curing metastatic disease. Herein, we
      examined effect of Thai propolis extract and its major constituent, chrysin, on
      hypoxic survival of 4T1 mouse breast cancer cells in vitro, and investigated its
      underlying mechanism. In vivo effect of chrysin on metastatic progression of
      cancer cells was studied, both as a single agent and in combination with another
      antimetastatic agent, agonistic monoclonal antibody targeting the DR5 TRAIL
      receptor (DR5 mAb). Thai propolis extract and chrysin decreased survival of 4T1
      cells after exposure to hypoxia (1% O2), for 2 days. Immunoblot analysis revealed
      that chrysin inhibited hypoxia-induced STAT3 phosphorylation without affecting
      HIF-1alpha protein level. Chrysin also abrogated hypoxia-induced VEGF gene
      expression as determined by qRT-PCR. The in vivo effect of chrysin was determined
      in a spontaneous metastasis mouse model of breast cancer, either alone or in
      combination with DR5 mAb. Daily oral administration of chrysin in Balb/c mice
      implanted with 4T1 cells significantly suppressed growth of lung metastatic
      colonies. Moreover, antimetastatic activity of DR5 mAb was enhanced when given in
      combination with chrysin. We demonstrate that chrysin has potential in
      controlling metastatic progression. 

PMID- 23969635
TI  - New optical method for enhanced detection of colon cancer by capsule endoscopy.
AB  - PillCam(r)COLON capsule endoscopy (CE), a non-invasive diagnostic tool of the
      digestive tract, has dramatically changed the diagnostic approach and has become
      an attractive alternative to the conventional colonoscopy for early detection of
      colorectal cancer. However, despite the significant progress and non-invasive
      detection capability, studies have shown that its sensitivity and specificity is
      lower than that of conventional colonoscopy. This work presents a new optical
      detection method, specifically tailored to colon cancer detection and based on
      the well-known optical properties of immune-conjugated gold nanorods (GNRs). We
      show, on a colon cancer model implanted in a chick chorioallantoic membrane
      (CAM), that this detection method enables conclusive differentiation between
      cancerous and normal tissues, where neither the distance between the light source
      and the intestinal wall, nor the background signal, affects the monitored signal.
      This optical method, which can easily be integrated in CE, is expected to reduce
      false positive and false negative results and improve identification of tumors
      and micro metastases. 

PMID- 23969636
TI  - The Imperative of Public Health Education: A Global Perspective.
AB  - This review positions public health as an endeavour that requires a high order of
      professionalism in addressing the health of populations; this requires investment
      in an educational capacity that is designed to meet this need. In the global
      context, the field has evolved enormously over the past half century, supported
      by institutions such as the World Bank, the World Health Organization and the
      Institute of Medicine. Operational structures are formulated by strategic
      principles, with educational and career pathways guided by competency frameworks,
      all requiring modulation according to local, national and global realities.
      Talented and well-motivated individuals are attracted by its multidisciplinary
      and transdisciplinary environment, and the opportunity to achieve interventions
      that make real differences to people's lives. The field is globally competitive
      and open to many professional backgrounds based on merit. Its competencies
      correspond with assessments of population needs, and the ways in which strategies
      and services are formulated. Thus, its educational planning is needs-based and
      evidence-driven. This review explores four public health education levels:
      graduate, undergraduate, continuing professional education and promotion of
      health literacy for general populations. The emergence of accreditation schemes
      is examined, focusing on their relative merits and legitimate international
      variations. The role of relevant research policies is recognized, along with the
      need to foster professional and institutional networks in all regions of the
      world. It is critically important for the health of populations that nations
      assess their public health human resource needs and develop their ability to
      deliver this capacity, and not depend on other countries to supply it.

PMID- 23969637
TI  - Relationship between the phase value of ESWAN and fractional anisotropy of
      diffusion tensor imaging in patients with cerebral microbleeds: preliminary
      results.
AB  - AIMS: The purpose of the present study was to measure phase values (PVs) and
      fractional anisotropy (FA) of cerebral microbleeds (CMBs) using phase and FA map,
      and to investigate the potential relationship between PVs and FAs in CMBs in
      vivo. METHODS: We retrospectively analyzed 30 patients with CMBs using enhanced
      T2*-weighted angiography and diffusion tensor imaging. The PVs and FAs of CMBs
      were measured and documented, and the mean FAs were compared between CMBs and the
      corresponding normal brain tissue. The mean PVs were correlated with FAs in CMBs
      in seven different brain regions. RESULTS: A total of 106 CMBs were defined, and
      the mean FA of the CMBs in white matter, EC/IC/CR, thalamus, and cerebellum were
      significantly lower than that of normal brain tissue in the control group
      (p<0.05). Positive correlations were observed between the PV and FA of CMBs in
      white matter, external capsule, internal capsule and corona radiata (r=0.70,
      0.38). CONCLUSION: Enhanced T2*-weighted angiography and diffusion tensor imaging
      sequence may be useful neuroimaging sequences that could reflect the severity of
      damage of white matter by measuring the FA of CMBs and provide useful reference
      data for the quantitative assessment of CMBs.

PMID- 23969638
TI  - Freedoms and rights.

PMID- 23969639
TI  - Needless needle loss.

PMID- 23969640
TI  - Unjust, relatively ignored.

PMID- 23969641
TI  - Diodontic implant.

PMID- 23969642
TI  - Tongue cancer subgroup.

PMID- 23969643
TI  - Different perspectives.

PMID- 23969644
TI  - Death of a pastry chef.

PMID- 23969651
TI  - Government to remove restriction on HIV-positive dentists.

PMID- 23969652
TI  - Managing the phase-down of amalgam: part II. Implications for practising
      arrangements and lessons from Norway.
AB  - The announcement of the Minamata Convention has triggered the lead into a phase
      down in the use of dental amalgam. This paper considers aspects of this
      development in the context of the experience of banning the use of dental amalgam
      in Norway. It is suggested that strong top-down leadership and joined-up working
      by all relevant stakeholders, including patients, may be one of the most
      important keys to an effective, seamless transition to the provision of
      preventatively orientated, patient-centred, minimally interventive operative
      dentistry, based on state-of-the-art selection and application of tooth-coloured
      restorative materials. The benefits of such a transition are considered to be an
      important goal for dentistry in the UK. 

PMID- 23969653
TI  - Needlestick and occupational exposure to infections: a compendium of current
      guidelines.
AB  - Needlestick and occupational exposure to infections is a constant threat in
      dental practice. Many blood-borne infections, including human immunodeficiency
      virus (HIV) infection, hepatitis B and hepatitis C, may be contracted through
      this route. We provide here a useful compendium for dental practitioners on
      current guidelines available to obviate such threats, as well as a simple
      flowchart on prophylactic measures that could be taken after an accidental
      exposure. 

PMID- 23969654
TI  - The use of diffuse laser photonic energy and indocyanine green photosensitiser as
      an adjunct to periodontal therapy.
AB  - Light-activated chemical therapy - generally known as photodynamic therapy (PDT) 
      has been developed within medicine, to allow the use of an applied agent
      (photosensitiser) that could be activated using laser photonic energy, leading to
      the destruction of target cellular structures. In clinical dentistry, PDT has
      been utilised within a wide scope of topical application in endodontic,
      periodontal and oral epithelial pathology where specifically, anti-bacterial
      action may prove useful. Underlying the complex and multi-factorial aetiology,
      periodontal disease remains of essentially-bacterial origin and anti-bacterial
      PDT (aPDT) has been investigated as an adjunctive to other periodontal treatment
      therapies. Of several topically-applied photosensitisers, one agent, indocyanine
      green, may be activated using a diode laser wavelength (810 nm) that is commonly
      available in clinical dental practice, to provide generalised bacteriocidal
      effect. Unlike antibiotics and antibacterial mouthwashes, the mode of action
      appears to be nonspecific to bacterial species and is linked to cell death
      through a process of oxidative stress. Additionally, indocyanine green has
      otherwise low toxicity to non-target host tissue and dental restorative
      materials. This paper explores the background to this therapy, its position
      within the broader delivery of periodontal treatment and the specific application
      of indocyanine green in clinical dental practice. 

PMID- 23969659
TI  - Summary of: Treatment of early caries lesions using biomimetic self-assembling
      peptides--a clinical safety trial.

PMID- 23969660
TI  - An investigation of complete denture teaching in the UK: part 1. A survey of
      undergraduate teaching.
AB  - AIM: This paper is the first in a series of two that investigate the
      undergraduate teaching of complete dentures in the UK. MATERIALS AND METHODS: A
      questionnaire was sent by email to 13 UK dental schools enquiring about the
      number of hours spent in the lecture theatre, laboratory and clinic. The schools
      were also asked to give their views about the preparedness of the new graduates
      for dealing with complete dentures in general practice. RESULTS: There was great
      disparity between schools in the overall number of lectures delivered. Two
      schools claimed 28 hours and the remainder varied between 6-15 hours. Four
      schools devoted more time to laboratory work whereas three schools spent more
      time in the clinic. One school reported no dedicated clinical time for complete
      dentures. There appears to be a regional variation with northern UK dental
      schools spending more time on the teaching of complete dentures. The quota for
      complete dentures varied from three in most schools to eight in one school and
      none in another. Comments from the dental schools varied from a reported lack of
      suitable complete denture cases, to concerns with insufficient curricular time
      devoted to the subject and a subsequent lack of clinical competence on
      graduation. Some schools have integrated complete denture teaching into the
      general prosthodontic course as it is considered inappropriate to teach different
      aspects of prosthetics in isolation. CONCLUSION: Competence in complete dentures
      falls short of what is expected. With a single exception all the schools seem to
      have low expectations for their undergraduate students to be practically trained
      and experienced in the production of complete dentures. Despite the advent of
      implants and the introduction of clinical dental technicians, there is and will
      continue to be a need for the competent treatment of the edentulous population by
      general practitioners.

PMID- 23969661
TI  - How do we measure quality in primary dental care?
AB  - In the second paper of a series exploring quality in primary dental care a way to
      measure quality in dentistry is considered. Unless there are valid and reliable
      tools to measure quality then quality can never be improved. Measurement tools
      need to be acceptable to patients if they are to be employed, as well as to busy
      practices in terms of practicality and costs. Examples such as the General
      Medical Practitioner's Quality Outcome Framework need to be understood to see if
      they can be translated to dentistry. 

PMID- 23969678
TI  - Philip Greene: 'in order to be a good dentist you must be a good periodontist'.
      Interview by Ruth Doherty.
AB  - British Society of Periodontology President Philip Greene discusses the
      considerable changes in periodontics over the past 40 years and suggests that the
      reward system for GDPs must change to allow the delivery of effective perio for
      patients. 

PMID- 23969679
TI  - Treatment of early caries lesions using biomimetic self-assembling peptides--a
      clinical safety trial.
AB  - OBJECTIVE: We previously reported that a rationally designed biomimetic self
      assembling peptide, P11-4, nucleated hydroxyapatite de novo and was apparently
      capable of in situ enamel regeneration following infiltration into caries-like
      lesions. Our present aim was to determine the safety and potential clinical
      efficacy of a single application of P11-4 on early enamel lesions. MATERIALS AND
      METHODS: Fifteen healthy adults with Class V 'white spot' lesions received a
      single application of P11-4. Adverse events and lesion appearances were recorded
      over 180 days. RESULTS: Patients treated with P11-4 experienced a total of 11
      adverse events during the study, of which two were possibly related to the
      protocol. Efficacy evaluation suggested that treatment with P11-4 significantly
      decreased lesion size (p = 0.02) after 30 days and shifted the apparent
      progression of the lesions from 'arrested/progressing' to 'remineralising' (p
      <0.001). A highly significant improvement in the global impression of change was
      recorded at day 30 compared with baseline (p <0.001). CONCLUSIONS: The results
      suggest that treatment of early caries lesions with P11-4 is safe, and that a
      single application is associated with significant enamel regeneration, presumably
      by promoting mineral deposition within the subsurface tissue.

PMID- 23969680
TI  - The impact of a community-based health education programme on oral cancer risk
      factor awareness among a Gujarati community.
AB  - OBJECTIVES: To determine any differences in oral cancer risk factor awareness and
      behaviour among first and second generation Gujarati muslims and to investigate
      the impact of a community-based health education programme on oral cancer risk
      factor awareness. DESIGN: Respondents completed a confidential, bilingual
      questionnaire in English and Gujarati regarding alcohol, tobacco, paan, sopari,
      paan masala and gutka use before and after a community-based health education
      programme on oral cancer risk factors. SETTING: Community Health Fair. Indian
      Muslim Welfare Association, Batley, West Yorkshire. SUBJECTS: Ninety-six male and
      female Gujarati muslims aged 16 to 81 years. MAIN OUTCOME MEASURES: Quantitative
      results on oral cancer risk factor awareness before and after a health education
      programme. Quantitative figures obtained from the questionnaire with regards to
      alcohol, tobacco, paan, sopari, paan masala and gutka usage. RESULTS: There were
      very low levels of alcohol consumption among Gujarati muslims. First generation
      Gujarati males consumed significantly more tobacco than second generation
      Gujarati males, difference in proportion 0.30 (0.03 to 0.56, p = 0.03). There was
      complete absence of paan use among Gujarati females. First generation Gujarati
      males consumed significantly higher amounts of sopari compared with their male
      counterparts in the second generation (p = 0.003). There were very low rates of
      paan masala use. Only first generation Gujarati males consumed gutka.
      Significantly more first generation males and females correctly identified all
      oral cancer risk factors after the health education intervention compared with
      baseline (difference 0.40, 95% CI 0.23 to 0.57, p = <0.001). Significantly more
      second generation males and females correctly identified all oral cancer risk
      factors after the health education intervention compared with baseline
      (difference 0.45, 95% CI 0.28 to 0.61, p = <0.001). CONCLUSION: Our study
      demonstrated significant differences in oral cancer risk factor awareness and
      practices among first and second generation Gujarati muslims and that a local
      community-based health education programme was effective in raising awareness.

PMID- 23969681
TI  - Cell-free circulating DNA as a novel biomarker in patients with the acute
      coronary syndrome.

PMID- 23969682
TI  - Metabolism: How sweet it is... .

PMID- 23969687
TI  - Metastasis: Active lymph nodes.

PMID- 23969688
TI  - Tumour microenvironment: Means of resistance.

PMID- 23969693
TI  - Zebrafish cancer: the state of the art and the path forward.
AB  - The zebrafish is a recent addition to animal models of human cancer, and studies
      using this model are rapidly contributing major insights. Zebrafish develop
      cancer spontaneously, after mutagen exposure and through transgenesis. The
      tumours resemble human cancers at the histological, gene expression and genomic
      levels. The ability to carry out in vivo imaging, chemical and genetic screens,
      and high-throughput transgenesis offers a unique opportunity to functionally
      characterize the cancer genome. Moreover, increasingly sophisticated modelling of
      combinations of genetic and epigenetic alterations will allow the zebrafish to
      complement what can be achieved in other models, such as mouse and human cell
      culture systems. 

PMID- 23969694
TI  - Hybrid optofluidic integration.
AB  - Complete integration of microfluidic and optical functions in a single lab-on
      chip device is one goal of optofluidics. Here, we demonstrate the hybrid
      integration of a PDMS-based fluid handling layer with a silicon-based optical
      detection layer in a single optofluidic system. The optical layer consists of a
      liquid-core antiresonant reflecting optical waveguide (ARROW) chip that is
      capable of single particle detection and interfacing with optical fiber.
      Integrated devices are reconfigurable and able to sustain high pressures despite
      the small dimensions of the liquid-core waveguide channels. We show the
      combination of salient sample preparation capabilities-particle mixing,
      distribution, and filtering-with single particle fluorescence detection.
      Specifically, we demonstrate fluorescent labelling of lambda-DNA, followed by
      flow-based single-molecule detection on a single device. This points the way
      towards amplification-free detection of nucleic acids with low-complexity
      biological sample preparation on a chip. 

PMID- 23969692
TI  - Disrupting proton dynamics and energy metabolism for cancer therapy.
AB  - Intense interest in the 'Warburg effect' has been revived by the discovery that
      hypoxia-inducible factor 1 (HIF1) reprogrammes pyruvate oxidation to lactic acid
      conversion; lactic acid is the end product of fermentative glycolysis. The most
      aggressive and invasive cancers, which are often hypoxic, rely on exacerbated
      glycolysis to meet the increased demand for ATP and biosynthetic precursors and
      also rely on robust pH-regulating systems to combat the excessive generation of
      lactic and carbonic acids. In this Review, we present the key pH-regulating
      systems and synthesize recent advances in strategies that combine the disruption
      of pH control with bioenergetic mechanisms. We discuss the possibility of
      exploiting, in rapidly growing tumours, acute cell death by 'metabolic
      catastrophe'. 

PMID- 23969695
TI  - beta1-adrenergic receptor and sphingosine-1-phosphate receptor 1 (S1PR1)
      reciprocal downregulation influences cardiac hypertrophic response and
      progression to heart failure: protective role of S1PR1 cardiac gene therapy.
AB  - BACKGROUND: The sphingosine-1-phosphate receptor 1 (S1PR1) and beta1-adrenergic
      receptor (beta1AR) are G-protein-coupled receptors expressed in the heart. These
      2 receptors have opposing actions on adenylyl cyclase because of differential G
      protein coupling. Importantly, both of these receptors can be regulated by the
      actions of G-protein-coupled receptor kinase-2, which triggers desensitization
      and downregulation processes. Although classic signaling paradigms suggest that
      simultaneous activation of beta1ARs and S1PR1s in a myocyte would simply result
      in opposing action on cAMP production, in this report we have uncovered a direct
      interaction between these 2 receptors, with regulatory involvement of G-protein
      coupled receptor kinase-2. METHODS AND RESULTS: In HEK (human embryonic kidney)
      293 cells overexpressing both beta1AR and S1PR1, we demonstrated that beta1AR
      downregulation can occur after stimulation with sphingosine-1-phosphate (an S1PR1
      agonist), whereas S1PR1 downregulation can be triggered by isoproterenol (a beta
      adrenergic receptor agonist) treatment. This cross talk between these 2 distinct
      G-protein-coupled receptors appears to have physiological significance, because
      they interact and show reciprocal regulation in mouse hearts undergoing chronic
      beta-adrenergic receptor stimulation and in a rat model of postischemic heart
      failure. CONCLUSIONS: We demonstrate that restoration of cardiac plasma membrane
      levels of S1PR1 produces beneficial effects that counterbalance the deleterious
      beta1AR overstimulation in heart failure.

PMID- 23969697
TI  - Fibrinogen: a circulating factor in search of its genetic architecture.

PMID- 23969699
TI  - Everolimus in combination with paclitaxel and carboplatin in patients with
      metastatic melanoma: a phase II trial of the Sarah Cannon Research Institute
      Oncology Research Consortium.
AB  - This phase II trial examined the efficacy and toxicity of first-line treatment
      with everolimus, paclitaxel, and carboplatin in patients with advanced melanoma.
      Seventy patients with metastatic or locally advanced unresectable melanoma who
      had been untreated previously with chemotherapy or targeted agents received first
      line treatment with everolimus (5 mg, orally, daily), paclitaxel (175 mg/m,
      intravenous, every 3 weeks), and carboplatin (area under the curve 6.0,
      intravenous, every 3 weeks). Response to treatment was assessed every 6 weeks;
      responding and stable patients received six cycles of paclitaxel and carboplatin,
      and subsequently continued single-agent everolimus until disease progression or
      unacceptable toxicity. Twelve patients (17%) showed objective responses (all
      partial); an additional 27 patients showed measurable tumor shrinkage. After a
      median follow-up of 15 months, the median progression-free survival was 4.0
      months (95% confidence interval 2.8-5.0 months); the median survival for the
      entire group was 10.1 months. Myelosuppression was the most common grade 3/4
      toxicity; 70% of patients experienced at least one episode of grade 3/4 toxicity
      while on study. Although this regimen was active in the first-line treatment of
      advanced melanoma, there was no suggestion of improved efficacy when compared
      with previous results with paclitaxel/carboplatin alone. Further study of this
      combination is not recommended. 

PMID- 23969698
TI  - Function and distribution of apolipoprotein A1 in the artery wall are markedly
      distinct from those in plasma.
AB  - BACKGROUND: Prior studies show that apolipoprotein A1 (apoA1) recovered from
      human atherosclerotic lesions is highly oxidized. Ex vivo oxidation of apoA1 or
      high-density lipoprotein (HDL) cross-links apoA1 and impairs lipid binding,
      cholesterol efflux, and lecithin-cholesterol acyltransferase activities of the
      lipoprotein. Remarkably, no studies to date directly quantify either the function
      or HDL particle distribution of apoA1 recovered from the human artery wall.
      METHODS AND RESULTS: A monoclonal antibody (10G1.5) was developed that equally
      recognizes lipid-free and HDL-associated apoA1 in both native and oxidized forms.
      Examination of homogenates of atherosclerotic plaque-laden aorta showed >100-fold
      enrichment of apoA1 compared with normal aorta (P<0.001). Surprisingly, buoyant
      density fractionation revealed that only a minority (<3% of total) of apoA1
      recovered from either lesions or normal aorta resides within an HDL-like particle
      (1.063<=d<=1.21). In contrast, the majority (>90%) of apoA1 within aortic tissue
      (normal and lesions) was recovered within the lipoprotein-depleted fraction
      (d>1.21). Moreover, both lesion and normal artery wall apoA1 are highly cross
      linked (50% to 70% of total), and functional characterization of apoA1
      quantitatively recovered from aorta with the use of monoclonal antibody 10G1.5
      showed ~80% lower cholesterol efflux activity and ~90% lower lecithin-cholesterol
      acyltransferase activity relative to circulating apoA1. CONCLUSIONS: The function
      and distribution of apoA1 in human aorta are quite distinct from those found in
      plasma. The lipoprotein is markedly enriched within atherosclerotic plaque,
      predominantly lipid-poor, not associated with HDL, extensively oxidatively cross
      linked, and functionally impaired.

PMID- 23969700
TI  - The synthesis, spectroscopy and X-ray single crystal structure of catena-[(MU
      anacardato)-copper(II)bipyridine][Cu2{(MU-O2CC6H3(o-OH)(o-C15H31)}4(NC5H5)2].
AB  - Hydrogenation of crude anacardic acid gave a transparent crystalline product on
      recrystallization. When reacted with copper nitrate in the presence of pyridine
      it produced green crystals of a pyridine adduct of a dimeric copper(II)
      anacardate with the copper acetate structure. The X-ray single crystal structures
      of both anacardic acid and the copper complex were determined. Magnetic studies
      have confirmed strong antiferromagnetic coupling between copper(II) centre in the
      dimer. The exchange coupling constant was determined to be J = -324 cm(-1). The
      EPR spectra of the polycrystalline product are consistent with spin S = 1. The
      zero-field splitting parameter and g tensor values are |D| = 0.36 cm(-1), g(||) =
      2.36 and g(?) = 2.06.

PMID- 23969701
TI  - Transient global amnesia associated with accidental high-frequency stimulation of
      the right hippocampus in deep brain stimulation for segmental dystonia.
AB  - We report on a 66-year-old woman with segmental dystonia treated with chronic
      bilateral deep brain stimulation of the globus pallidus internus, in whom
      accidental high-voltage, high-frequency stimulation induced an episode of
      transient global amnesia (TGA) via an electrode contact which was misplaced in
      the right hippocampus. A possible mechanism underlying this TGA episode may have
      been the inhibition of local neuronal activity or fiber activation by high
      current density via direct electrical stimulation of hippocampal structures.
      While a unifying etiology of TGA has not been proven so far, our case
      demonstrates a possible link between focal electrical stimulation of hippocampal
      structures and the full clinical picture of the syndrome. 

PMID- 23969702
TI  - Bovine apolipoprotein (apo)A-I displays more enhanced antioxidant and anti
      atherosclerotic activity in lipid-free and lipid-bound states than human and
      porcine apoA-I.
AB  - Apolipoprotein A-I (apoA-I) is a major component of high-density lipoprotein
      (HDL), which displays anti-atherosclerotic activity in plasma. In the current
      study, we compared the functional and structural characteristics of human, bovine
      and porcine apoA-I as regards their antioxidant ability and protein stability. In
      the lipid-free state, the immunoreactivity of bovine and porcine apoA-I differed
      from that of human apoA-I and bovine and porcine apoA-I exhibited greater
      resistance to denaturation induced by urea treatment. Bovine apoA-I showed the
      weakest binding ability of dimyristoyl phosphatidylcholine; however, bovine apoA
      I formed slightly larger reconstituted HDL (rHDL) particles with palmitoyl oleoyl
      phosphatidylcholine, with a higher number of apoA-I-containing particles. Bovine
      and porcine apoA-I comprised of pentameric structures, whereas human apoA-I in
      the rHDL state consisted of trimeric structures. Although apoA-I from all three
      species showed a similar content of alpha-helicity in the lipid-free state
      (approximately 53%), bovine apoA-I showed a lower alpha-helicity content
      (approximately 66%) compared with human apoA-I (approximately 74%) in the rHDL
      state. Bovine apoA-I was more resistant to denaturation and glycation upon
      treatment with urea and fructose, respectively. Furthermore, bovine apoA-I showed
      a greater inhibition of cupric ion-mediated low-density lipoprotein (LDL)
      oxidation and uptake of acetylated LDL by macrophages compared with human or
      porcine apoA-I in the lipid-free and lipid-bound states. In conclusion, bovine
      apoA-I has unique functional properties in the lipid-free and lipid-bound states,
      and displays significantly enhanced anti-atherosclerotic activity. 

PMID- 23969704
TI  - Ureterocele: antenatal diagnosis and management.
AB  - Ureteroceles are cystic dilations of the intravesical submucosal ureter. Most
      cases are associated with complete ureteral and renal duplication, and
      association with ureterohydronephrosis is frequent. The authors describe the 4
      cases of fetal ureterocele diagnosed from March 2008 to March 2012. Mean
      gestational age at diagnosis was 23 weeks (16-34 weeks). One of 4 cases
      progressed to severe hydronephrosis with megacystis and was referred to a Fetal
      Medicine Center for fetoscopy and laser ureterocelotomy. The remaining 3 cases
      did not need fetal therapy. Mean gestational age at delivery was 37 weeks. One
      case abandoned follow-up; 2 children were submitted to cystoscopic ureterocele
      incision and the child submitted to fetal therapy needed heminephrectomy due to
      recurrent urinary tract infections. In those 3 cases renal function was
      preserved. When a fetal ureterocele is diagnosed, close sonographic surveillance
      should be offered to monitor the possible urinary tract obstruction and assess
      the need for prenatal intervention. Fetal diagnosis is important to program the
      timing of delivery and postnatal care. 

PMID- 23969705
TI  - Topical treatment of neuropathic pain.
AB  - Pikes Peak Hospice and Palliative Care, Inc., provides care for more than 200
      patients with terminal disease who reside at home, in long-term care facilities,
      in assisted living facilities, or in its acute-care Inpatient Unit. Over the past
      4 years, its pharmacy has evolved to provide individualized compounded
      preparations to meet the unique and complex needs of these patients. An integral
      part of this evolution was development and implementation of topical treatment
      for pain. These patients often have multiple medical conditions and complicated
      health issues. Nearly 50% of patients in the care of Pikes Peak Hospice receive a
      topical compound to treat any of a variety of conditions, including neuropathies,
      muscle skeletal pain, wound pain, agitation, and anxiety. Topical compounds give
      practitioners another option in managing patient maladies and, in many instances,
      compounded topicals have proven as effective, if not more effective, than
      commercially available products. In some cases, patients have been able to stop
      oral pain medications or reduce their dose because the topical preparation is so
      effective. All in all, the topical preparations described in this article have
      been invaluable to our patients' comfort and an indispensable option for
      practitioners. 

PMID- 23969706
TI  - Compounded local anesthetics to minimize pain from medical procedures.
AB  - Many procedures do not have to be painful. There are several available
      pharmacological options, both commercial and compounded, for providing local
      anesthesia and thus minimizing the fear and stress associated with these
      procedures. No patient should suffer because the clinician lacks the knowledge or
      comfort level necessary to provide adequate analgesia during painful medical
      procedures. Compounding pharmacists can prepare local and topical anesthetics for
      clinics, emergency departments, patient-care units, and physicians' offices to
      keep on hand for medical emergencies and procedures; this reduces the waiting
      period for patients, allows procedures to be performed efficiently, and improves
      patient care. 

PMID- 23969707
TI  - Dilution and compounding of ziconotide for intrathecal administration.
AB  - Intrathecal therapy is an established treatment option for patients with severe
      chronic pain who do not receive adequate relief from less invasive methods.
      Ziconotide is the only nonopioid analgesic approved by the U.S. Food and Drug
      Administration for intrathecal administration. Ziconotide is approved for
      monotherapy only, but combination intrathecal therapy is considered an acceptable
      treatment option by experts in the field. When ziconotide is administered as
      monotherapy, the stability exceeds the refill intervals recommended in the
      ziconotide prescibing information. Compounding ziconotide with other intrathecal
      drugs speeds ziconotide degradation, but the stability loss does not increase
      patient risk for withdrawal symptoms, because ziconotide dose reductions are not
      associated with adverse effects and the drugs compounded with ziconotide remained
      stable in a series of studies. Results from in vitro studies suggest that the
      stability of ziconotide can be maximized by diluting commercial ziconotide
      formulations as little as possible, decreasing the concentration(s) of the
      drug(s) compounded with ziconotide, and compounding ziconotide with powders
      (rather than solutions) of other intrathecal drugs. Because oxygen speeds
      ziconotide degradation, removing dissolved oxygen by bubbling nitrogen through
      diluted or compounded solutions improves ziconotide stability. By incorporating
      these recommendations into standardized protocols for diluting and compounding
      ziconotide, clinicians can help ensure that patients receive safe and cost
      effective intrathecal ziconotide treatment. 

PMID- 23969708
TI  - Pharmacy compounding at the University of Connecticut: secundem artem et
      scientia.
AB  - The curriculum of the University of Connecticut School of Pharmacy continues to
      evolve just as the practice of pharmacy evolves. This is especially true in the
      practice of compounding, which has re-emerged as a respected art and science. The
      practice of compounding focuses on pharmaceutical elegance but also requires
      pharmacists to use their professional judgment based on limited data to assess
      the stability and efficacy of a compound before dispensing the preparation. The
      University's basic curriculum facilitates learning proper techniques and
      formulation, and the Advanced Compounding elective challenges students to master
      the evaluation of literature in the area of comounded preparations. While
      encouraging students to learn from mistakes, this elective allows students to
      gain confidence with techniques and available resources, empowering them to think
      creatively and improve patient care as they become active compounding
      pharmacists. 

PMID- 23969709
TI  - Developing and implementing a clinical pharmacy rotation in a community
      compounding pharmacy.
AB  - Specialty Medicine Compounding Pharmacy participates in the pharmacy student
      preceptor programs of Ohio Northern University and the University of Michigan.
      The pharmacy has developed a rotation program with two main emphases, developing
      a core set of compounding skills and learning new administrative skills. While
      compounding should be the main focus of any clinical pharmacy rotation program,
      preceptors are in a unique position to teach students skills that they may never
      have the opportunity to learn elsewhere. This article explains how to develop a
      rotation program that gives the student a well-rounded learning experience that
      encompasees the art of compounding and more. 

PMID- 23969710
TI  - Microbial air-sampling equipment, part 1: meeting United States pharmacopeia
      chapter 797 standards.
AB  - The most recent changes to Chapter 797 of the United States Pharmcopeia-National
      Formulary initiated an intense controversy about the frequency of cleanroom air
      sampling that is required to prevent the contamination of sterile preparations.
      For compounders who must purchase an air sampler to use in the cleanroom, choices
      abound. Included in this article are a review of United States Pharmacopeia
      National Formulary requirements that pertain to air sampling, a discussion of how
      recent revision to Chapter 797 affect air sampling and patient safety, and, for
      easy reference, a table that features specifications for various models of
      microbial air samplers. 

PMID- 23969711
TI  - Communication with pharmacy technicians: how to reduce stress and improve
      pharmacy operations.
AB  - Analysis of interviews with certified pharmacy technicians revealed that they
      experience work-related stressors related to the need for accuracy, workload
      expansion, and customer interaction. Three types of supportive communication
      (i.e., instrumental , emotional, informational) are discussed as methods to
      reduce the negative impact of these stressors on pharmacy operations. 

PMID- 23969712
TI  - Obtaining accreditation by the pharmacy compounding accreditation board, part 3:
      developing a program of qualtity assurance and continuous qualtiy improvement.
AB  - Before a compounding pharmacy can receive accreditation from the Pharmacy
      Compounding Accreditation Board, the pharmacy must show evidence of both quality
      assurance activities and continuous quality improvement activities. Although
      quality assurance data gathering and monitoring can be integrated into pharmacy
      activities fairly easily, the coninuous quality improvement program may take a
      little more time and effort to implement . Before integrating these programs,
      compounding pharmacists must have a complete understanding of the differences
      between these two programs. Even if accreditation with the Pharmacy Compounding
      Accreditation Board is not being considered, it is important that compounding
      pharmacies have these two programs implemented. In the long run, it will pay off
      in higher quality services, error prevention, and perhaps greater efficiency of
      pharmacy operations. 

PMID- 23969713
TI  - Litigating the legality of compounding: the medical center pharmacy case.
AB  - The question of whether all compounded drugs are "new drugs" has been disputed in
      the United states for over 15 years. The Federal Food, Drug, and Cosmetic Act
      generally requires that "new drugs" obtain U.S. Food and Drug Administration
      approval before being sold in the U.S. Between 1938 and the late 1980s, the U.S.
      Food and Drug Adminsitration did not asert that compounded drugs are subject to
      the drug provisions. Then the U.S.Food and Drug Administration developed and
      advanced a new theory. As articulated in a 1989 memorandum by a U.S. Food and
      Drug Administration attorney, the U.S. Food and Drug Administration could take
      the position that compounded drugs were new drugs and therefore subject to new
      drug approval requirements. Although the memorandum acknowledged that this
      represented a significant change in policy, the U.S.Food and Drug Administration
      adopted this legal theory. Their position that compounded drugs are new drugs led
      to a clash between the agency and compounding pharmacies. Congress appeared to
      settle this dispute in 1997 when it passed the Food and Drug Administration
      Modernization Act. This law contained a provision expempting pharmacies from the
      new drug approval requirements (and two other requirements) if they met certain
      critieria. Although the U.S. Food and Drug Administration has continued to
      maintain that is will not assert the "unapproved new drug" theory against the
      traditional compounding of drugs, it has invoked the "new drug" theory in many
      warning letters to pharmacies, including a series of heavily publicized warning
      letters issued the day before oral argument in the Medical Center Pharmacy case
      to the validity of the U.S. Food and Drug Administration's interpretation. The
      Fifth Circuit decision in the Medical Center Pharmcy case will provide an answer.
      It may not, however, be the final answer. 

PMID- 23969714
TI  - Web 2.0 and health 2.0: are you in?
AB  - With over 6 billion web pages, over $100 billion in online sales every year in
      the U.S. alone and the average growth rate of online purchasing exceeding 26%
      over the last 5 years, the Internet is a powerful business tool. Today's shopper
      sees your actual pharmacy location and your Internet presence as one and the
      same. One study showed that 82% of the consumers surveyed who had a single
      frustrating experience online with a retailer would not return to the site for
      future dealings. A bad experience online made 28% of those surveyed unlikely to
      return to the retail location of the business, and over 55% said a bad online
      experience would have a negative impact on their overall opinion of the retailer.
      Web 2.0 refers to the social networking applications of the internet, Health 2.0
      to its special health applications. Taking your Internet presence to the 2.0
      level must be balanced with all of the other demands you are facing-but be aware
      that it's happening all around you. 

PMID- 23969715
TI  - Quality-control analytical methods: a process verification model for quality
      assurance in a compounding pharmacy.
AB  - There are virtually thousands of examples of uses of the "process" model of
      quality assurance in modern industrial applications, so the precedent for this
      type of quality-assurance in modern industrial applications, so the precedent for
      this type of quality-assurance and quality-control program is well estabilished
      and thoroughly accepted. The initiation of a process verification model for
      quality assurance and control, and the documentation involved in the process,
      constitute appropriate proof that a compounding pharmacy is developing quality
      preparations, which in turn can be used to improve a pharmacy's operation. 

PMID- 23969696
TI  - Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects
      identifies 23 fibrinogen-associated Loci but no strong evidence of a causal
      association between circulating fibrinogen and cardiovascular disease.
AB  - BACKGROUND: Estimates of the heritability of plasma fibrinogen concentration, an
      established predictor of cardiovascular disease, range from 34% to 50%. Genetic
      variants so far identified by genome-wide association studies explain only a
      small proportion (<2%) of its variation. METHODS AND RESULTS: We conducted a meta
      analysis of 28 genome-wide association studies including >90 000 subjects of
      European ancestry, the first genome-wide association meta-analysis of fibrinogen
      levels in 7 studies in blacks totaling 8289 samples, and a genome-wide
      association study in Hispanics totaling 1366 samples. Evaluation for association
      of single-nucleotide polymorphisms with clinical outcomes included a total of 40
      695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030
      controls for stroke, and 3208 cases and 46 167 controls for venous
      thromboembolism. Overall, we identified 24 genome-wide significant (P<5*10(-8))
      independent signals in 23 loci, including 15 novel associations, together
      accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis
      highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen
      genes and pathways related to inflammation, adipocytokines, and thyrotrophin
      releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a
      few loci were significantly associated with coronary artery disease, the combined
      effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was
      not significant for coronary artery disease, stroke, or venous thromboembolism.
      CONCLUSIONS: We identify 23 robustly associated fibrinogen loci, 15 of which are
      new. Clinical outcome analysis of these loci does not support a causal
      relationship between circulating levels of fibrinogen and coronary artery
      disease, stroke, or venous thromboembolism.

PMID- 23969716
TI  - Basics of compounding: considerations for implementing United States pharmacopeia
      chapter 797 pharmaceutical compounding-sterile preparations, part 7: microbial
      contamination risk levels, 12-hour use, and immediate use.
AB  - This article discusses the types of contamination that may occur when compounding
      personnel prepare, handle, or store sterile preparations, as discussed in United
      States Pharmacopeia Chapter 797 Pharmaceutical Compounding-Sterile Preparations.
      Contamination may be microbial, physical, or chemical, and all these are possible
      when sterile preparations are made. Microbial contamination may be fungal or
      bacterial. The most frequently identified microbial organisms in sterile
      preparations are spores and endotoxins. Chemical and physical contamination
      includes foreign objects, chemicals, physical matter, nonsterile components or
      objects, and airborne particles, objects, or matter from environments with
      uncontrolled air quality. Thorough knowledge of the possible sources of
      contamination can help in implementing the steps and processes to avoid
      contamination. The purpose of this article is to review the contamination risk
      level categories as disussed in Chapter 797. 

PMID- 23969718
TI  - Chemical stability of naltrexone hydrochloride injection.
AB  - The chemical stability of naltrexone hydrochloride injection was studied by using
      a stability-indicating high-performance liquid chromatographic assay method that
      was developed in our laboratory. The concentrations of the drug were related
      directly to peak heights, and the percent relative standard deviation based on
      five injections was 1.0. The products of decomposition and excipients present in
      the dosage form did not interfere with the developed assay method. The injection
      was stable for at least 42 days when stored in clear glass vials at room
      temperature. The pH value of the injection decreased from 6.4 to 5.5 after 42
      days of storage; the physical appearance of the injection did not change during
      the study period. 

PMID- 23969717
TI  - Evaluation of the percutaneous absorption of promethazine hydrochloride, in
      vitro, using the human ex vivo skin model.
AB  - For several years, pharmacists have been using vehicles such as Pluronic lecithin
      organogel and Lipoderm for the delivery of medication, including promethazine,
      through the skin. This study evaluated the percutaneous absorption
      pharmacokinetics of promethazine hydrochloride 25 mg/g in Pluronic lecithin
      organogel and the commercial base Lipoderm,in vitro, in human ex vivo skin, using
      the finite dose technique and Franz Diffusion Cells. Due to the polar nature of
      promethazine hydrochloride, it was theorized that this drug would present a
      transdermal challenge for these two commonly utilized compounding bases. An
      amount of 5 mcL/cm squared of each formulation was applied to triplicate sections
      of skin from three different ex vivo skin donors. At 4, 8, 12, 24, 32, and 48
      hours post-application, the reservoir solution in the Franz Cell was removed and
      analyzed. Lipoderm performed better than Pluronic lecithin organogel based on
      total absorption into the reservoir solution (2.86% +/- 0.79 vs. 1.73% +/-0.85)
      (P less than 0.2). Total permeation through and beyond the stratum corneum
      (epidermis, dermis, and reservoir solution) after 48 hours was significantly
      greater for Lipoderm than for Pluronic lecithin organogel (23.06% +/- 3.33 vs.
      10.31% +/- 5.44), with the Student's t-test showing statistical significance (P
      less than 0.001). These data indicate that promethazine hydrochloride does
      penetrate into and through human ex vivo skin in vitro using Lipoderm and
      Pluronic lecithin organogel, with Lipoderm showing better results. 

PMID- 23969719
TI  - Compatibility of caspofungin acetate injection with other drugs simulated y-site
      coadministration.
AB  - The physical compatibility of caspofungin acetate injection with selected other
      drugs during simulated Y-site coadministration was evaluated by visual
      observation and turbidity measurement. Five-milliliter samples of caspofungin
      acetate 0.7 mg/mL in 0.9% sodium chloride injection were combined with 5 mL of 67
      other drugs including antineoplastics,analgesics, anti-infectives, and supportive
      care drugs, undiluted or diluted in 0.9% sodium chloride injection or 5% dextrose
      injection, and with a parenteral nutrition admixture. Visual examinations were
      performed with the unaided eye in normal laboratory fluorescent light and with a
      Tyndall beam (high-intensity monodirectional light beam) to enhance visualization
      of small particles and low-level turbidity. The turbidity of each sample was
      measured as well. The sample mixtures were evaluated immediately and at 1 and 4
      hours after preparation. Nineteen of the drugs tested and the parenteral
      nutrition admixture were incompatible with caspofungin acetate 0.7 mg/mL during
      the 4-hour observation period. The remaining drugs were compatible for at least 4
      hours. Gross precipitation or turbidity changes visible in normal diffuse room
      light with the unaided eye occurred with 18 drugs and with the parenteral
      nutrition admixture. Microprecipitation of particulates not visible with the
      unaided eye occurred with cytarabine. The measured turbidity of the caspofungin
      acetate control solutions and the compatible test samples remained essentially
      unchanged throughout the observation period. In combination with caspofungin
      acetate, 48 drugs and a parenteral nutrition admixture were considered to be
      physically compatible. In contrast, 19 drugs with the parenteral nutrition
      admixture exhibited frank precipitation or microparticulate formation within 4
      hours and should not be simultaneously administered via Y-site with caspofungin
      acetate. 

PMID- 23969720
TI  - PostScription: A Contemporary Perspective on Compounding Education.

PMID- 23969721
TI  - Bladder cancer cell-derived exosomes inhibit tumor cell apoptosis and induce cell
      proliferation in vitro.
AB  - Exosomes are small membrane vesicles released by a variety of mammalian cells
      into the extracellular space and are involved in cell-to-cell signaling. This
      study aimed to investigate the effects of bladder cancer cell-derived exosomes on
      the regulation of tumor cell viability and apoptosis, as well as the underlying
      molecular events. Exosomes were purified from the supernatants of human bladder
      cancer T24 cell cultures. Transmission electron microscopy was used to confirm
      their morphology and western blot analyses determined the protein content of
      cells. Subsequently, bladder cancer cell lines were treated with different
      concentrations of exosomes. Tumor cell viability was shown to be reduced, as
      detected by the Cell Counting Kit-8 assay. Annexin V/flow cytometric assays
      showed that exosomes inhibited apoptosis of bladder cancer cell lines in a dose-
      and time-dependent manner. Exosomes were demonstrated to upregulate the
      expression of Bcl-2 and Cyclin D1 proteins, but reduce the levels of Bax and
      caspase-3 proteins in these cells. Moreover, exosomes dose-dependently increased
      the expression of phosphorylated Akt and extracellular signal-regulated protein
      kinase (ERK). In conclusion, this study demonstrated that bladder cancer cell
      derived exosomes inhibited tumor cell apoptosis, which was associated with the
      activation of Akt and ERK pathway genes, suggesting that tumor-derived exosomes
      are involved in bladder cancer progression. Inhibition of exosome formation and
      release may therefore be a novel strategy in future treatment of bladder cancer.

PMID- 23969722
TI  - 18FDG-PET to assess recurrence and long term survival in patients with malignant
      melanoma.
AB  - AIM: To assess the diagnostic and prognostic value of FDG-PET/CT in the follow-up
      of malignant melanoma in comparison to the serum protein S100B. PATIENTS AND
      METHODS: A total of ninety patients with either low-risk or high-risk malignant
      melanoma, respectively, were included in this study. The follow-up of the
      patients was pursuant with the guidelines of the German Dermatological
      Association. The diagnostic accuracy and diagnostic power were determined for
      PET/CT and for the serum protein S100B. RESULTS: In 28 of the 90 patients PET/CT
      was positive in the follow up, 47 patients had an elevated Serum S100B level.
      Sensitivity, specificity, PPV and NPV of PET/CT for the total groups of patients
      were 87%, 93%, 87% and 93%. The corresponding values for the serum protein S100B
      were 65%, 52%, 43% and 74%, respectively. PET/CT positive patients showed a
      significantly (p < 0.001) higher risk of melanoma associated death compared to
      patients with PET/CT negative findings. No statistical significance could be
      found in the 5 year survival rate between the S100B positive and S100B negative
      patients. CONCLUSION: PET/CT is suitable to confirm or exclude recurrences and
      can be used to assess the prognosis in melanoma patients. The diagnostic accuracy
      and the prognostic power is much higher compared to the serum protein S100B.

PMID- 23969723
TI  - The effect of duration post-migraine on visual electrophysiology and visual field
      performance in people with migraine.
AB  - PURPOSE: In between migraine attacks, some people show visual field defects that
      are worse when measured closer to the end of a migraine event. In this cohort
      study, we consider whether electrophysiological responses correlate with visual
      field performance at different times post-migraine, and explore evidence for
      cortical versus retinal origin. METHODS: Twenty-six non-headache controls and 17
      people with migraine performed three types of perimetry (static, flicker and blue
      on-yellow) to assess different aspects of visual function at two visits conducted
      at different durations post-migraine. On the same days, the pattern
      electroretinogram (PERG) and visual evoked response (PVER) were recorded.
      RESULTS: Migraine participants showed persistent, interictal, localised visual
      field loss, with greater deficits at the visit nearer to migraine offset. Spatial
      patterns of visual field defect consistent with retinal and cortical dysfunction
      were identified. The PERG was normal, whereas the PVER abnormality found did not
      change with time post-migraine and did not correlate with abnormal visual field
      performance. CONCLUSIONS: Dysfunction on clinical tests of vision is common in
      between migraine attacks; however, the nature of the defect varies between
      individuals and can change with time. People with migraine show markers of both
      retinal and/or cortical dysfunction. Abnormal visual field sensitivity does not
      predict abnormality on electrophysiological testing.

PMID- 23969724
TI  - Phosphoramidate synthesis via copper-catalysed aerobic oxidative coupling of
      amines and H-phosphonates.
AB  - The copper-catalysed oxidative coupling of amines and H-phosphonates to produce
      phosphoramidates has been achieved using CuI as the catalyst and O2 (present in
      air) as the sole oxidant. 

PMID- 23969725
TI  - An experimental animal model for abdominal fascia healing after surgery.
AB  - BACKGROUND: Incisional hernia (IH) is a well-known complication after abdominal
      surgical procedures. The exact etiology of IH is still unknown even though many
      risk factors have been suggested. The aim of this study was to create an animal
      model of a weakly healed abdominal fascia that could be used to evaluate the
      actively healing fascia. Such an animal model may promote future research in the
      prevention of IH. METHODS: 86 male Sprague-Dawley rats were used to establish a
      model involving six experiments (experiments A-F). Mechanical testing of the
      breaking strength of the healed fascia was performed by testing tissue strips
      from the healed fascia versus the unincised control fascia 7 and 28 days
      postoperatively. RESULTS: During the six experiments a healing model was created
      that produced significantly weaker coherent fascia when compared with the control
      tissue measured in terms of mechanical breaking strength. This new animal model
      employed myofascial closing after a full thickness abdominal incision using a
      running suture with fast-absorbable suture material. This technique produced a
      weak myofascial layer compared with the control tissue measured in terms of
      breaking strength after both 7 and 28 days. CONCLUSION: It was possible to create
      a healed but weak abdominal fascia in rats with a minimum of defects after
      incision using a running suture technique in the fascia. In contrast to other
      models, regular tissue defects were absent, and the model can therefore be used
      to evaluate the changes, both histological and mechanical, in the actively
      healing fascia, which may lead to incisional herniation. Furthermore, the model
      may also be used to study interventions performed to promote healing. This
      contrasts with existing models with regular fascia defects, which are not well
      suited for this purpose.

PMID- 23969727
TI  - Comment on 'Beta-blockers increase response to chemotherapy via direct anti
      tumour and anti-angiogenic mechanisms in neuroblastoma'.

PMID- 23969726
TI  - MiR-17-92 and miR-221/222 cluster members target KIT and ETV1 in human
      gastrointestinal stromal tumours.
AB  - BACKGROUND: Gastrointestinal stromal tumours (GIST) are characterised by high
      expression of KIT and ETV1, which cooperate in GIST oncogenesis. Our aim was to
      identify microRNAs that are deregulated in GIST, have a role in GIST
      pathogenesis, and could potentially be used as therapeutic tool. METHODS:
      Differentially expressed microRNAs between primary GIST (n=50) and
      gastrointestinal leiomyosarcomas (GI-LMS, n=10) were determined using
      microarrays. Selected microRNA mimics were transfected into GIST-882 and GIST-T1
      cell lines to study the effects of microRNA overexpression on GIST cells.
      Luciferase reporter assays were used to establish regulation of target genes by
      selected microRNAs. RESULTS: MiR-17-92 and miR-221/222 cluster members were
      significantly (P<0.01) lower expressed in GIST vs GI-LMS and normal
      gastrointestinal control tissues. MiR-17/20a/222 overexpression in GIST cell
      lines severely inhibited cell proliferation, affected cell cycle progression,
      induced apoptosis and strongly downregulated protein and--to a lesser extent-
      mRNA levels of their predicted target genes KIT and ETV1. Luciferase reporter
      assays confirmed direct regulation of KIT and ETV1 by miR-222 and miR-17/20a,
      respectively. CONCLUSION: MicroRNAs that may have an essential role in GIST
      pathogenesis were identified, in particular miR-17/20a/222 that target KIT and
      ETV1. Delivering these microRNAs therapeutically could hold great potential for
      GIST management, especially in imatinib-resistant disease.

PMID- 23969728
TI  - Reply: Comment on 'Beta-blockers increase response to chemotherapy via direct
      anti-tumour and anti-angiogenic mechanisms in neuroblastoma'--beta-blockers are
      potent anti-angiogenic and chemo-sensitising agents, rather than cytotoxic drugs.

PMID- 23969729
TI  - Reduced expression of bone morphogenetic protein receptor IA in pancreatic cancer
      is associated with a poor prognosis.
AB  - BACKGROUND: The expression of SMAD4, the central component of the transforming
      growth factor-beta (TGF-beta) and bone morphogenetic protein (BMP) signalling
      pathways, is lost in 50% of pancreatic cancers and is associated with a poor
      survival. Although the TGF-beta pathway has been extensively studied and
      characterised in pancreatic cancer, there is very limited data on BMP signalling,
      a well-known tumour-suppressor pathway. BMP signalling can be lost not only at
      the level of SMAD4 but also at the level of BMP receptors (BMPRs), as has been
      described in colorectal cancer. METHODS: We performed immunohistochemical
      analysis of the expression levels of BMP signalling components in pancreatic
      cancer and correlated these with survival. We also manipulated the activity of
      BMP signalling in vitro. RESULTS: Reduced expression of BMPRIA is associated with
      a significantly worse survival, primarily in a subset of SMAD4-positive cancers.
      In vitro inactivation of SMAD4-dependent BMP signalling increases proliferation
      and invasion of pancreatic cancer cells, whereas inactivation of BMP signalling
      in SMAD4-negative cells does not change the proliferation and invasion or leads
      to an opposite effect. CONCLUSION: Our data suggest that BMPRIA expression is a
      good prognostic marker and that the BMP pathway is a potential target for future
      therapeutic interventions in pancreatic cancer.

PMID- 23969731
TI  - Nitrous oxide reduction-coupled alkene-alkene coupling catalysed by
      metalloporphyrins.
AB  - Porphyrin complexes of iron, manganese and cobalt catalysed reductive
      dimerization of alkenes with NaBH4 under N2O. The reaction system using Fe(III)
      porphyrin generated an Fe(I) porphyrin intermediate that reduced N2O to
      regenerate Fe(III) porphyrin.

PMID- 23969730
TI  - P2Y2 receptor promotes cell invasion and metastasis in prostate cancer cells.
AB  - BACKGROUND: Our previous study demonstrated that extracellular adenosine 5'
      triphosphate (ATP) stimulated prostate cancer cell invasion via P2Y receptors.
      However, the purinergic receptor subtype(s) involved in this process remains
      unclear. Here we aimed to determine whether P2Y2, one subtype of P2Y receptors,
      was involved in the invasion and metastasis of prostate cancer cells, and
      elucidated the underlying mechanism. METHODS: RNAi was introduced to silence the
      expression of P2Y2. In vitro invasion and migration assays and in vivo
      experiments were carried out to examine the role of P2Y2 receptor in cell
      invasion and metastasis. cDNA microarray was performed to identify the
      differentially expressed genes downstream of ATP treatment. RESULTS: P2Y2 was
      significantly expressed in the prostate cancer cells. Knockdown of P2Y2 receptor
      suppressed cell invasion and metastasis in vitro and in vivo. Further experiments
      identified that ATP could promote IL-8 and Snail expression and inhibit E
      cadherin and Claudin-1 expression. Knockdown of P2Y2 receptor affected the
      expression of these EMT/invasion-related genes in vitro and in vivo. CONCLUSION:
      P2Y2 receptor promotes cell invasion and metastasis in prostate cancer cells via
      some EMT/invasion-related genes. Thereby, P2Y2 receptor could be a potential
      therapeutic target for the treatment of prostate cancer.

PMID- 23969732
TI  - Transposable elements in fish chromosomes: a study in the marine cobia species.
AB  - Rachycentron canadum, a unique representative of the Rachycentridae family, has
      been the subject of considerable biotechnological interest due to its potential
      use in marine fish farming. This species has undergone extensive research
      concerning the location of genes and multigene families on its chromosomes.
      Although most of the genome of some organisms is composed of repeated DNA
      sequences, aspects of the origin and dispersion of these elements are still
      largely unknown. The physical mapping of repetitive sequences on the chromosomes
      of R. canadum proved to be relevant for evolutionary and applied purposes.
      Therefore, here, we present the mapping by fluorescence in situ hybridization of
      the transposable element (TE) Tol2, the non-LTR retrotransposons Rex1 and Rex3,
      together with the 18S and 5S rRNA genes in the chromosome of this species. The
      Tol2 TE, belonging to the family of hAT transposons, is homogeneously distributed
      in the euchromatic regions of the chromosomes but with huge colocalization with
      the 18S rDNA sites. The hybridization signals for Rex1 and Rex3 revealed a semi
      arbitrary distribution pattern, presenting differentiated dispersion in
      euchromatic and heterochromatic regions. Rex1 elements are associated
      preferentially in heterochromatic regions, while Rex3 shows a scarce distribution
      in the euchromatic regions of the chromosomes. The colocalization of TEs with 18S
      and 5S rDNA revealed complex chromosomal regions of repetitive sequences. In
      addition, the nonpreferential distribution of Rex1 and Rex3 in all
      heterochromatic regions, as well as the preferential distribution of the Tol2
      transposon associated with 18S rDNA sequences, reveals a distinct pattern of
      organization of TEs in the genome of this species. A heterogeneous chromosomal
      colonization of TEs may confer different evolutionary rates to the
      heterochromatic regions of this species.

PMID- 23969738
TI  - A role for IL-17 in age-related macular degeneration.

PMID- 23969736
TI  - Metalloproteinases and their natural inhibitors in inflammation and immunity.
AB  - Over the past 50 years, steady growth in the field of metalloproteinase biology
      has shown that the degradation of extracellular matrix components represents only
      a fraction of the functions performed by these enzymes and has highlighted their
      fundamental roles in immunity. Metalloproteinases regulate aspects of immune cell
      development, effector function, migration and ligand-receptor interactions. They
      carry out ectodomain shedding of cytokines and their cognate receptors. Together
      with their endogenous inhibitors TIMPs (tissue inhibitor of metalloproteinases),
      these enzymes regulate signalling downstream of the tumour necrosis factor
      receptor and the interleukin-6 receptor, as well as that downstream of the
      epidermal growth factor receptor and Notch, which are all pertinent for
      inflammatory responses. This Review discusses the metalloproteinase family as a
      crucial component in immune cell development and function. 

PMID- 23969739
TI  - Prelude to a successful site visit, part 2.
AB  - This column provides information on accreditation for nursing programs of all
      types. Readers may submit questions to the Accreditation Commission for Education
      in Nursing. General questions of interest to a wide audience will be addressed in
      this column, whereas more specific questions or those requiring confidentiality
      will be answered directly. 

PMID- 23969737
TI  - Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of
      the beginning.
AB  - The field of HIV-1 vaccine research has seen a renaissance with the
      identification of antibodies that neutralize most circulating HIV-1 strains. An
      understanding of the structural mode of target recognition that these antibodies
      use and the immune pathways that lead to their development is emerging. This
      knowledge has provided fundamental insights into the pathways that elicit broadly
      neutralizing antibodies and provides a foundation for active and passive
      immunization strategies to prevent HIV-1 infection.

PMID- 23969741
TI  - Thoughts regarding innovations in nursing education, part 1.
AB  - Many new nursing leaders assuming deanships, assistant, or interim deanships have
      limited education, experience, or background to prepare them for the job. To
      assist new deans and those aspiring to be deans, the authors of this department
      offer survival tips based on their personal experiences and insights. They
      address common issues, challenges, and opportunities that face academic executive
      teams, such as negotiating an executive contract, obtaining faculty lines,
      building effective work teams, managing difficult employees, and creating nimble
      organizational structure to respond to changing consumer, healthcare delivery,
      and community needs. The authors welcome counterpoint discussions with readers. 

PMID- 23969743
TI  - Enhancing learning: A comparison of lecture and gaming outcomes.
AB  - Contrary to what we anticipated, our outcomes indicated that learning and
      satisfaction with learning were no different between the traditional lecture
      group and the educational gaming group. Learners in the gaming group scored on
      the examination just as well as, but no higher than, did those in the lecture
      group. Similarly, students in the gaming group were just as, but no more,
      satisfied with their learning than were students in the lecture group. Of note,
      both teaching/learning strategies were shown to be effective for learning with
      students earning a B average on the examination. Likewise, students in both
      groups were very satisfied with their respective teaching/learning strategies.
      Given that our assessment did not support gaming as a superior teaching/learning
      strategy over lecture, what remains now is the need for a longitudinal study to
      determine if there are differences in long-term learning. As we implement
      creative methods of instruction, it is also important to test their effectiveness
      to ensure that the teaching-learning process is evidence based.

PMID- 23969744
TI  - FaceTime: a virtual pathway between research and practice.

PMID- 23969745
TI  - Implementation of a teaching assistant program in graduate nursing education.
AB  - Identifying and educating students who have an interest and talent to be future
      educators is a challenge throughout academia, including nursing. The ideal
      scenario is to identify students early in their education and construct or
      scaffold a unique relationship between professor and student. The authors discuss
      a teaching assistant model, implemented in a nursing graduate program, which
      augments the education process while developing potential future nursing
      educators. 

PMID- 23969747
TI  - Social bullying in nursing academia.
AB  - Social bullying has gained attention in the contemporary literature and
      increasing scrutiny in nursing academia. With a paucity of research on the topic
      in nursing, the authors asked nursing faculty about the phenomenon of being
      bullied by faculty colleagues or academic administrators. They discuss their
      study and its outcomes and implications for academic work lives, recruitment, and
      retention. 

PMID- 23969748
TI  - Study abroad programs: Using alumni and graduate students as affiliate faculty.
AB  - To expand student appreciation of global health and diversity, many schools of
      nursing offer study abroad programs. However, this type of labor-intensive
      program can be difficult in light of faculty shortages and constrained resources.
      The authors discuss how these issues were addressed using alumni and graduate
      students as affiliate teachers in 3 clinical study abroad settings. 

PMID- 23969749
TI  - Implementing team-based learning in a nurse practitioner curriculum.
AB  - Team-based learning (TBL) is an innovative, learner-centered teaching strategy
      that promotes active learning. The authors describe their experience with
      implementing TBL in an adult-gerontology acute and primary care course for nurse
      practitioners as well as their evaluation of student outcomes. 

PMID- 23969750
TI  - Pinstructive ideas: Using a social networking bulletin board for nursing
      education.
AB  - The advancement of Web 2.0 tools has created multiple avenues in which nursing
      students can search for and share information. Nursing faculty should consider
      using these advancements to create teaching-learning activities that engage
      students. The authors discuss the use of Pinterest, a visual social bookmarking
      site that was used to promote active and engaged learning in a course designed to
      prepare future nursing educators who, as faculty, will feel comfortable embracing
      this technology. Steps that faculty can take in planning, implementing, and
      evaluating Pinterest activities as well as lessons learned and suggestions for
      other use of Pinterest are discussed. 

PMID- 23969751
TI  - Using the flipped classroom in graduate nursing education.
AB  - A flipped classroom is a pedagogical model that involves having students view
      online lectures, read current evidence-based articles, and complete text readings
      prior to class. Students then come to class ready to actively engage in
      collaborative learning through case scenarios, small group discussion, or other
      meaningful, interactive activities. The flipped classroom model described here
      was an overwhelming success for both students and faculty. 

PMID- 23969753
TI  - Making high-fidelity simulation relevant to the home setting.
AB  - The integration of high-fidelity simulation can prepare nurses to respond to
      realistic patient situations and be ready for their roles as professional nurses.
      A learning framework such as Understanding by Design can be used to develop
      simulations that are cohesive with course and program outcomes. The authors
      discuss their use of this framework to develop a simulation in a community health
      course. 

PMID- 23969754
TI  - Using a first-year seminar to introduce nursing.
AB  - First-year seminar courses designed to aid the transition of freshmen students to
      the collegiate experience are commonplace requirements at many 4-year
      institutions. The authors describe the development, implementation, and outcomes
      of a first-year seminar course with introductory nursing content. 

PMID- 23969755
TI  - Cultural awareness: Enhancing clinical experiences in rural Appalachia.
AB  - Students often work with clients from a cultural group different than their own.
      This is especially true for students completing clinical practica in Appalachia,
      where there is a culture unique to that geographic area. To prepare for this
      unique setting, common cultural scenarios experienced in the clinical setting
      must be addressed to help provide culturally appropriate patient care while
      developing required clinical competencies. Although applicable to most nursing
      students, the author discusses culturally specific approaches to clinical care of
      clients from Appalachia, specifically applied to nurse practitioner students,
      preceptors, and clinical faculty. 

PMID- 23969757
TI  - Promoter methylation status of the FHIT gene and Fhit expression: association
      with HER2/neu status in breast cancer patients.
AB  - Aberrant DNA methylation has been recognized to contribute to breast
      carcinogenesis, and promoter hypermethylation of several tumor suppressor genes
      has been correlated with decreased gene expression. The fragile histidine triad
      (FHIT) gene is a putative tumor suppressor gene in breast and other types of
      cancer, and loss of Fhit expression has been observed in breast cancer. The aim
      of the present study was to evaluate the association between methylation of the
      FHIT gene and its expression in breast cancer, and to investigate whether
      methylation and expression of the FHIT gene correlates with clinicopathological
      characteristics in relation to human epidermal growth factor receptor 2 (HER2)
      status. Pyrosequencing of bisulfite-treated DNA was performed to study the
      methylation status of the FHIT gene in 60 breast cancer samples. We examined the
      expression of Fhit using tissue microarrays by immunohistochemical staining. FHIT
      methylation was detected in 96.7% and the positive expression rate of Fhit was
      87.3% of the patients. The mean methylation level of the FHIT gene was associated
      with intratumoral inflammation. Methylation level of the FHIT gene had no
      significant differences according to molecular subtypes. Loss of Fhit expression
      was associated with large tumor size, basal-like subtype and positive expression
      of EGFR. In HER2-negative breast cancer, loss of Fhit expression was
      significantly associated with tumor size, estrogen receptor status and Ki-67
      proliferation index. No significant correlation between methylation of the FHIT
      gene and its expression was observed in the present study. Our results suggest
      that loss of Fhit expression in breast cancer is associated with poor prognostic
      features, and it is also relevant to the results in HER2-negative breast cancer.
      Further studies with larger sample sizes and longer follow-up are required to
      clarify the predictive and prognostic value of Fhit expression and the FHIT gene
      methylation status in breast cancer. 

PMID- 23969759
TI  - The relationship between cell-free circulating DNA and inflammation in acute
      coronary syndrome.

PMID- 23969758
TI  - Older people and digital disengagement: a fourth digital divide?
AB  - Digital technologies are becoming more pervasive in all areas of society.
      Enabling everyone to have access and capability to use the Internet and
      associated digital technologies, summed up in the term 'digital inclusion', is
      seen to have wide-ranging benefits to the individual, to the economy and to
      society. For older people, being digitally included can help them to maintain
      their independence, social connectedness and sense of worth in the face of
      declining health or limited capabilities, as well as also offering new
      opportunities to improve their quality of life. At present however, access to the
      technology and to the benefits is not equally distributed either between or
      within nations, and older people tend to be on the 'wrong' side of what is termed
      the 'digital divide'. Governments globally are developing strategies to promote
      digital inclusion and indeed Internet uptake is increasing steadily, including
      amongst older people. However, such strategies have focussed on getting people
      online, and there appears to be an assumption that once someone is online they
      will remain 'digitally engaged'. In fact statistics show that some users give up
      using the Internet, and there is emerging evidence that older people are more
      vulnerable to the factors which can lead to this outcome. The authors see this
      phenomenon as a potential but largely unrecognised 'fourth digital divide' which
      has serious implications for social inclusion. The objectives of this article are
      (a) to raise awareness of the phenomenon of digital disengagement by considering
      some of the emerging evidence, (b) to explore some of the potential implications
      of not recognising and therefore not addressing the needs of the digitally
      disengaged older population, and (c) to reveal the prevailing gap in knowledge
      which future research should address. 

PMID- 23969761
TI  - Early local differentiation of the cell wall matrix defines the contact sites in
      lobed mesophyll cells of Zea mays.
AB  - BACKGROUND AND AIMS: The morphogenesis of lobed mesophyll cells (MCs) is highly
      controlled and coupled with intercellular space formation. Cortical microtubule
      rings define the number and the position of MC isthmi. This work investigated
      early events of MC morphogenesis, especially the mechanism defining the position
      of contacts between MCs. The distributions of plasmodesmata, the hemicelluloses
      callose and (1 -> 3,1 -> 4)-beta-d-glucans (MLGs) and the pectin epitopes
      recognized by the 2F4, JIM5, JIM7 and LM6 antibodies were studied in the cell
      walls of Zea mays MCs. METHODS: Matrix cell wall polysaccharides were
      immunolocalized in hand-made sections and in sections of material embedded in LR
      White resin. Callose was also localized using aniline blue in hand-made sections.
      Plasmodesmata distribution was examined by transmission electron microscopy.
      RESULTS: Before reorganization of the dispersed cortical microtubules into
      microtubule rings, particular bands of the longitudinal MC walls, where the MC
      contacts will form, locally differentiate by selective (1) deposition of callose
      and the pectin epitopes recognized by the 2F4, LM6, JIM5 and JIM7 antibodies, (2)
      degradation of MLGs and (3) formation of secondary plasmodesmata clusterings.
      This cell wall matrix differentiation persists in cell contacts of mature MCs.
      Simultaneously, the wall bands between those of future cell contacts
      differentiate with (1) deposition of local cell wall thickenings including
      cellulose microfibrils, (2) preferential presence of MLGs, (3) absence of callose
      and (4) transient presence of the pectins identified by the JIM5 and JIM7
      antibodies. The wall areas between cell contacts expand determinately to form the
      cell isthmi and the cell lobes. CONCLUSIONS: The morphogenesis of lobed MCs is
      characterized by the early patterned differentiation of two distinct cell wall
      subdomains, defining the sites of the future MC contacts and of the future MC
      isthmi respectively. This patterned cell wall differentiation precedes cortical
      microtubule reorganization and may define microtubule ring disposition.

PMID- 23969762
TI  - Ultrastructure of stomatal development in early-divergent angiosperms reveals
      contrasting patterning and pre-patterning.
AB  - BACKGROUND AND AIMS: Angiosperm stomata consistently possess a pair of guard
      cells, but differ between taxa in the patterning and developmental origin of
      neighbour cells. Developmental studies of phylogenetically pivotal taxa are
      essential as comparative yardsticks for understanding the evolution of stomatal
      development. METHODS: We present a novel ultrastructural study of developing
      stomata in leaves of Amborella (Amborellales), Nymphaea and Cabomba
      (Nymphaeales), and Austrobaileya and Schisandra (Austrobaileyales), representing
      the three earliest-divergent lineages of extant angiosperms (the ANITA-grade).
      KEY RESULTS: Alternative developmental pathways occur in early-divergent
      angiosperms, resulting partly from differences in pre-patterning and partly from
      the presence or absence of highly polarized (asymmetric) mitoses in the stomatal
      cell lineage. Amplifying divisions are absent from ANITA-grade taxa, indicating
      that ostensible similarities with the stomatal patterning of Arabidopsis are
      superficial. In Amborella, 'squared' pre-patterning occurs in intercostal
      regions, with groups of four protodermal cells typically arranged in a rectangle;
      most guard-mother cells are formed by asymmetric division of a precursor cell
      (the mesoperigenous condition) and are typically triangular or trapezoidal. In
      contrast, water-lily stomata are always perigenous (lacking asymmetric
      divisions). Austrobaileya has occasional 'giant' stomata. CONCLUSIONS: Similar
      mature stomatal phenotypes can result from contrasting morphogenetic factors,
      although the results suggest that paracytic stomata are invariably the product of
      at least one asymmetric division. Loss of asymmetric divisions in stomatal
      development could be a significant factor in land plant evolution, with
      implications for the diversity of key structural and physiological pathways.

PMID- 23969763
TI  - Efficient prevention strategy against the development of a palmar-plantar
      erythrodysesthesia during chemotherapy.
AB  - BACKGROUND: Pegylated liposomal doxorubicin (PLD) is a highly efficient
      chemotherapeutic; however, it induces dermal side effects such as palmar-plantar
      erythrodysesthesia (PPE) in up to 80% of cases, probably by being emitted with
      the sweat onto the skin surface. AIM: The aim of the present study was to examine
      whether a topically applied ointment containing antioxidants with a high radical
      protection factor is able to prevent the formation of PPE. METHODS: Twenty
      patients suffering from ovarian carcinoma and treated with PLD were observed.
      RESULTS: 60% of the patients tolerated the regular application of the cream and
      developed no PPE. The remaining 40% interrupted the application. Six of them
      developed PPE and resumed ointment application thereafter. In these cases the PPE
      disappeared or was strongly reduced. CONCLUSION: The results of the observation
      clearly demonstrate that topical application of the ointment is an efficient
      strategy against the development of PPE during chemotherapy with PLD.

PMID- 23969764
TI  - Estriol: Women's Choice vs. A Manufacturer's Greed.
AB  - The U.S. Food and Drug Administration recently took action to "halt" the
      compounding of hormone preparations that contain estriol, an action requested in
      a citizen petition filed by Wyeth Pharmaceuticals. If the Food and Drug
      Administration, with the support of Wyeth is successful in its efforts, women
      throughout the U.S. who rely on compounded hormones containing estriol will have
      to discontinue their prescribed treatment. The International Academy of
      Compounding Pharmacists is engaged in ongoing outreach to ensure that members of
      Congress recognize the importance of protecting pharmacy compounding for the
      health and well-being of hteir constituents. Significant progress has been made
      with the recent introduction of a congressional resolution in support of estriol.

PMID- 23969765
TI  - Transdermal progesterone: effects on menopausal symptoms and on thrombotic,
      anticoagulant, and inflammatory factors in postmenopausal women.
AB  - Conventional hormone replacement therapy increases a woman's risk of thrombotic
      events as evidenced in large prospective clinical trials, including HERS I and
      the Women's Health Initiative. A possible mechanism for this is the unfavorable
      net effects of conjugated equine estrogens and medroxyprogesterone acetate on
      factors involved in hemostatic balance and inflammation. The objective of this
      study was to examine the short-term effects of transdermal progesterone on
      menopausal symptoms and serum levels of hemostatic, inflammatory, and immune
      signaling factors. In a prospective, randomized, double-blinded, placebo
      controlled, crossover study, 30 healthy postmenopausal women received either 20
      mg/day of transdermal progesterone or placebo for 4 weeks, followed by a 4-week
      washout period, and were then crossed over to receive either placebo or active
      drug for an additional 4 weeks. Baseline, 4-week follow-up, and end-of-study
      values were obtained for the Greene Climacteric Scale, and for serum levels of
      total factor VII:C, factor VIIa, factor V, fibrinogen, antithrombin III,
      plasminogen activator inhibitor-1, C-reactive protein, interleukin-6, matrix
      metalloproteinase-9, and tumor necrosis factor-a. Transdermal progesterone
      significantly improved Greene Climacteric Scale scores. In sharp contrast to
      previous studies of conventional hormone replacement therapy, no detrimental
      effect was observed on any of the hemostatic or inflammatory components examined.
      Administration of transdermal progesterone at a daily dose of 20 mg significantly
      relieves menopausal symptoms in postmenopausal women without adversely altering
      prothrombotic potential. We suggest, therefore, that this treatment be seriously
      considered as an effective and safe alternative clinical therapy for women
      suffering from menopausal symptoms. 

PMID- 23969766
TI  - The magic of magnesium.
AB  - Magnesium is the fourth most abundant mineral in the body and is essential to
      good health. Approximately 50% of total body magnesium is found in bone. The
      other half is found predominantly inside cells of body tissues and organs. Only
      1% of magnesium is found in blood. Studies performed on the importance of
      magnesium and the medical conditions that may arise from inadequate magnesium in
      the body have increased the interest of magnesium supplementation. Magnesium, an
      important electrolyte needed for proper muscle, nerve, and enzyme function, is
      also used as a supplement to relieve premenstrual symptoms related to mood
      changes. Studies indicate that some of the medical conditions that may arise from
      inadequate magnesium are hypertension, hear arrhythmias, diabetes, osteoporosis,
      migraines, premature ejaculation, premenstrual syndrome, and insomnia, to list a
      few. Compounding pharmacists can consult with patients and assist them with
      magnesium supplements that are prepared specifically for their health needs. 

PMID- 23969767
TI  - Beyond-use dating, labeling, delivery, and storage of compounded and repackaged
      medications in a hospital or institutional setting.
AB  - Batch-preparation of compounded medications in anticipation of orders or
      prescriptions and repackaging of medications into unit-dose packages are
      necessary in the hospital or institutional setting in order to provide around-the
      clock patient care. Professional judgment by the compounding pharmacist(s) and
      adherence to specific standards and guidelines set by the Joint Commission on
      Accreditation of Healthcare Organizations; United States Pharmacopeial
      convention, Inc.; and American Society of Health-System Pharmacists help to
      ensure that such medications retain their expected potency and are properly
      labeled, stored, and administered. 

PMID- 23969768
TI  - Microbial air-sampling equipment, part 2: experiences of compounding pharmacists.
AB  - The most recent changes to Chapter 797 of the United States Pharmacopeia-National
      Formulary initiated an intense controversy about the frequency of cleanroom air
      sampling that is required to prevent the contamination of sterile preparations.
      For compounders who must purchase an air sampler to use in the cleanroom, choices
      abound. This article summarizes discussions from compounding pharmacists and
      their experiences with air sampling devices. 

PMID- 23969770
TI  - Using Readily Available Technology to Start or Enhance Pharmacy-based
      Immunization.
AB  - Although the concept is relatively new in the U.S., the increase in the number of
      states permitting pharmacists to administer vaccines to their patients suggests
      that policymakers realize the importance and health benefits impact of pharmacy
      involvement in immunization delivery. The authors of this article recommend that
      compounding pharmacists consider the importance of offering immunization services
      in their community and have described several ways to use readily available
      technology to enhance immunization services. 

PMID- 23969769
TI  - Recommendations for overcoming barriers to medication therapy management
      implementation, part 1: review of literature.
AB  - As a required service of the Medicare Modernization Act of 2003, medication
      therapy management services must be offered by all Part D prescription drug plan
      sponsors in order to improve overall knowledge of medication usage for targeted
      patients. Those targeted patients include patients who have multiple chronic
      diseases, have been prescribed several covered Part D medications, and are paying
      at least $4,000 in out-of-pocket expenses for their medication each year. This
      article serves as a literature review of medication therapy management services
      and serves as an introduction to a study conducted by the authors concerning some
      of the barriers and recommendations to overcome such barriers encountered by
      Indiana pharmacists. 

PMID- 23969771
TI  - Quality-control analytical methods: homogeneity of dosage forms.
AB  - Content uniformity is the degree of consistency in the amount of the drug
      substance among dosage units. There are two ways to determine content uniformity
      according to United States Pharmacopeial Chapter 905: by means of Content
      Uniformity or Weight Variation methods. It is essenetial that compounding
      pharmacists know the different methods, how they work, and when to use each
      method to determine the content uniformity of their individual dosages. 

PMID- 23969772
TI  - Basics of compounding: considerations for implementing United States pharmacopeia
      chapter 797 pharmaceutical compounding-sterile preparations, part 8: stability
      and beyond-use dating.
AB  - Beyond-use-dates for sterile preparations are divided into two categories. If a
      program of sterility testing is not in place, then the short beyond-use dates
      specified in United States Pharmacopeia Chapter 797 for the different risk levels
      are to be used. If a program of sterility testing is in place, then the beyond
      use dates described in United States Pharmacopeia Chpater 795 for stability of
      various types of preparations/formulations can be used, which are somewhat longer
      than those in Chapter 797. Beyond-use dates are established on the basis of
      chemical and physical aspects of a compounded preparation. If a sterility testing
      program is in place, then each compounded preparation is considered "sterile" and
      the areas of concern are chemical and physical stability. In manufacturing, not
      every dosage unit is tested, only a sample. Similarly, only a sample of
      compounded preparations is tested. A sterility testing program must be in place
      to demonstrate that compounding proceures are under control. If a longer beyond
      use date is needed, then appropriate and specific stability studies of the
      compounded preparation must be undertaken. A very generalized difference between
      Chapter 795 and Chapter 797 is the requirement for sterility. The majority of
      Chapter 797 is involved with the requirements necessary to achieve and/or
      maintain sterility in compounded preparations and includes standards for the
      facility, equipment materials, personnel, and training. 

PMID- 23969773
TI  - Lack of commercial oral drug formulations for children in two hospital group
      purchasing agreements in france and Canada.
AB  - There are a limited number of commercial oral pediatric drug formulations on the
      market. The incidence of available commercial oral formulations for children has
      not been studied to date. This study compared the number and the characteristics
      of oral pediatric drug formulations listed on two hospital group purchasing
      agreements for the two large urban areas (e.g., Paris and Montreal), valid on
      April 1, 2006. Variables collected were the brand and the generic name product,
      the anatomical therapeutic chemical classification, the drug formulation, and the
      dispensing tool. Throughout this study, we identified that there was a total of
      191 and 151 commercial oral pediatric drug formulations corresponding to 127 and
      94 generic name products, respectively in Paris and Montreal. The three main
      anatomical therapeutic chemical classification classes are alimentary tract and
      metabolism drugs, systemic anti-infectives, and drugs acting on nervous system.
      There are only 47 generic names common to both group purchasing agreements. Also,
      our study provides examples of discrepancies between countries in terms of
      availability of commercial oral drug formulation for children. Market
      globalization should contribute to reduce these differences in the limited number
      of commercial oral pediatric drug formulations. 

PMID- 23969774
TI  - Physical and chemical stability of palonosetron hydrochloride with glycopyrrolate
      and neostigmine during simulated y-site administration.
AB  - The objective of this study was to evaluate the physical and chemical stability
      of undiluted palonosetron hydrochloride 50 mcg/mL when mixed with undiluted
      glycopyrrolate 0.2 mg/mL and neostigmine methylsulfate 0.5 mg/mL during simulated
      Y-site administration. Duplicate test samples were prepared by admixing 7.5 mL of
      palonosetron hydrochloride with 7.5 mL of glycopyrrolate and neostigmine
      methylsulfate injections. Physical stability was assessed by using a multi-step
      evaluation procedure that included both turbidimetric and particulate
      measurements and visual inspection. Chemical stability was assessed by using a
      multi-step evalutation procedure that included both turbidimetric and particulate
      measurements and visual inspection. Chemical stability was assessed by using
      stability-indicating high-performance liquid chromatography analytical techniques
      based on the determination of drug concentrations. Evaluations were perfromed
      initially upon mixing and 1 and 4 hours after mixing. The samples were clear and
      colorless when viewed with a Tyndall beam. Measured turbidity remained unchanged
      and particulate content was low and exhibited little change. High-performance
      liquid chromatography analysis found palonosetron hydrochloride and both
      glycopyrrolate and neostigmine methylsulfate remained stable throughout the 4
      hour test with no drug loss. Palonosetron hydrochloride is physically compatible
      and chemically stable with glycopyrrolate and neostigmine methylsulfate during
      simulated Y-site administration. 

PMID- 23969775
TI  - Chemical stability of perphenazine in two commercially available vehicles for
      oral liquid dosage forms.
AB  - The chemical stability of perphenazine in two commercially available vehicles for
      oral liquid dosage forms was studied by using a stability-indicating high
      performance liquid chromatographic assay method that was developed in our
      laboratory. The results indicate that the recommended beyond-use date of 180 days
      in Ora-Sweet syrup vehicle (final pH of the dosage form was 4.2) is not valid for
      this product. However, in Humco's simple syrup (final pH of the dosage form was
      4.5), perphenazine was stable for at least 183 days. The decomposition of
      perphenazine followed first order law. The decomposition constant at room
      temperature in Ora-Sweet syrup vehicle was 2.3 times higher (0.0007 per day)
      versus in Hucmco's simple syrup (0.0003 per day). The pH values of both dosage
      forms remained constant, and the physical appearance of both dosage forms did not
      change during this study period. For a stable oral liquid dosage form did not
      change during this study period. For a stable oral liquid dosage form of
      perphenazine, the pH value is very critical. 

PMID- 23969776
TI  - It is Not Just What You Say...But How You Say It!

PMID- 23969777
TI  - Are forensic experts biased by the side that retained them?
AB  - How objective are forensic experts when they are retained by one of the opposing
      sides in an adversarial legal proceeding? Despite long-standing concerns from
      within the legal system, little is known about whether experts can provide
      opinions unbiased by the side that retained them. In this experiment, we paid 108
      forensic psychologists and psychiatrists to review the same offender case files,
      but deceived some to believe that they were consulting for the defense and some
      to believe that they were consulting for the prosecution. Participants scored
      each offender on two commonly used, well-researched risk-assessment instruments.
      Those who believed they were working for the prosecution tended to assign higher
      risk scores to offenders, whereas those who believed they were working for the
      defense tended to assign lower risk scores to the same offenders; the effect
      sizes (d) ranged up to 0.85. The results provide strong evidence of an allegiance
      effect among some forensic experts in adversarial legal proceedings. 

PMID- 23969778
TI  - The interactive effect of anger and disgust on moral outrage and judgments.
AB  - The two studies reported here demonstrated that a combination of anger and
      disgust predicts moral outrage. In Study 1, anger toward moral transgressions
      (sexual assault, funeral picketing) predicted moral outrage only when it co
      occurred with at least moderate disgust, and disgust predicted moral outrage only
      when it co-occurred with at least moderate anger. In Study 2, a mock-jury
      paradigm that included emotionally disturbing photographs of a murder victim
      revealed that, compared to anger, disgust was a more consistent predictor of
      moral outrage (i.e., it predicted moral outrage at all levels of anger).
      Furthermore, moral outrage mediated the effect of participants' anger on their
      confidence in a guilty verdict--but only when anger co-occurred with at least a
      moderate level of disgust--whereas moral outrage mediated the effect of
      participants' disgust on their verdict confidence at all levels of anger. The
      interactive effect of anger and disgust has important implications for
      theoretical explanations of moral outrage, moral judgments in general, and legal
      decision making.

PMID- 23969779
TI  - High-performance supercapacitor and lithium-ion battery based on 3D hierarchical
      NH4F-induced nickel cobaltate nanosheet-nanowire cluster arrays as self-supported
      electrodes.
AB  - A facile hydrothermal method is developed for large-scale production of three
      dimensional (3D) hierarchical porous nickel cobaltate nanowire cluster arrays
      derived from nanosheet arrays with robust adhesion on Ni foam. Based on the
      morphology evolution upon reaction time, a possible formation process is
      proposed. The role of NH4F in formation of the structure has also been
      investigated based on different NH4F amounts. This unique structure significantly
      enhances the electroactive surface areas of the NiCo2O4 arrays, leading to better
      interfacial/chemical distributions at the nanoscale, fast ion and electron
      transfer and good strain accommodation. Thus, when it is used for supercapacitor
      testing, a specific capacitance of 1069 F g(-1) at a very high current density of
      100 A g(-1) was obtained. Even after more than 10,000 cycles at various large
      current densities, a capacitance of 2000 F g(-1) at 10 A g(-1) with 93.8%
      retention can be achieved. It also exhibits a high-power density (26.1 kW kg(-1))
      at a discharge current density of 80 A g(-1). When used as an anode material for
      lithium-ion batteries (LIBs), it presents a high reversible capacity of 976 mA h
      g(-1) at a rate of 200 mA g(-1) with good cycling stability and rate capability.
      This array material is rarely used as an anode material. Our results show that
      this unique 3D hierarchical porous nickel cobaltite is promising for
      electrochemical energy applications.

PMID- 23969780
TI  - Use of prolactin receptor antagonist to better understand prolactin regulation of
      pituitary homeostasis.
AB  - The anterior pituitary is permanently regulated by processes of apoptosis and
      proliferation in order to maintain tissue homeostasis. Several factors have been
      implicated in this regulation and lately, prolactin (PRL) has been included into
      that list. However, since PRL is secreted by anterior pituitary lactotropes, the
      actual outcome of its autocrine/paracrine actions on pituitary cells has remained
      difficult to assess. The availability of the pure PRL receptor antagonist Del1-9
      G129R-hPRL has been helpful to circumvent this problem. While PRL has been
      traditionally associated with increased cell proliferation, recent studies
      revealed that this hormone actually induces apoptosis and decreases proliferation
      of anterior pituitary cells, by mechanisms involving the PRL receptor. The aim of
      this short review is to overview our current understanding of the regulation of
      pituitary homeostasis by PRL. Moreover, studies involving Del1-9-G129R-hPRL have
      helped anticipate to what extent future treatments involving PRL receptor
      inhibitors may interfere with processes regulated by PRL at the central level.

PMID- 23969781
TI  - Development of the Heart Failure Screening Tool (Heart-FaST) to measure barriers
      that impede engagement in self-care.
AB  - BACKGROUND: Screening for self-care capacity is advocated before applying
      educational strategies. No screening tool has been specifically developed to
      assess barriers that impede engagement in self-care in people with heart failure.
      Earlier conceptual work (InCOGNITO) identified NYHA class, mild cognitive
      impairment and depressive symptoms as barriers that impede engagement in HF self
      care. AIMS: Study aims were: 1) to develop the Heart Failure Screening Tool
      (Heart-FaST) as a means of assessing three critical barriers to self-care; 2) to
      assess the content validity of the Heart-FaST; and 3) to test the feasibility of
      implementing the Heart-FaST in clinical practice. METHODS: The Heart-FaST was
      developed from barriers identified in previous research (InCOGNITO) and from
      expert panel consensus. Content validity was assessed by examining the proportion
      of experts who scored each item as relevant. RESULTS: The InCOGNITO study
      indicated that four cognitive tasks, seven emotional questions and NYHA
      functional class were significantly correlated with the self-care scales:
      maintenance, management and confidence. These factors were used to create the
      Heart-FaST items. Consensus on wording and items to be included in the Heart-FaST
      was reached after two rounds of panel discussion. All items had an item-level
      content validity index >= 0.78. High scores on each barrier (physical, cognitive
      and emotional functioning) suggest poor self-care and the need for more intensive
      disease management efforts. CONCLUSION: The Heart-FaST measures three critical
      barriers that impede engagement in self-care. In clinical practice this tool may
      assist in individually tailoring educational and support strategies to promote
      effective heart failure self-care.

PMID- 23969782
TI  - Anti-inflammatory effects of kudingcha methanol extract (Ilex kudingcha C.J.
      Tseng) in dextran sulfate sodium-induced ulcerative colitis.
AB  - The present study aimed to investigate the anti-inflammatory effects of Ilex
      kudingcha C.J. Tseng methanol extracts (KME) on 3% dextran sulfate sodium (DSS)
      induced ulcerative colitis (UC) in mice (C57BL/6J strain). Body weight, disease
      activity index (DAI), colon length, colon weight to length ratio, colonic
      myeloperoxidase (MPO), glutathione (GSH) and malondialdehyde (MDA) levels were
      measured. Histological changes were observed by hematoxylin and eosin staining.
      Colonic levels of tumor necrosis factor-alpha (TNF-alpha), interleukin(IL)-1beta
      and IL-6 were measured with an enzyme-linked immunosorbent assay. The mRNA
      expression of TNF-alpha, IL-1beta, -6, inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) in the colon tissue, was quantified by RT-PCR. KME
      significantly suppressed DSS-induced body weight loss, colon length shortening
      and decreased the colon weight to length ratio. It also resulted in increased GSH
      and reduced MPO and MDA levels in the colon tissue. Histological observation
      suggested that KME prevented edema, mucosal damage and loss of crypts, which are
      induced by DSS. In addition, KME decreased the levels of TNF-alpha, IL-1beta and 
      6 in the colon tissues, while inhibiting the mRNA expression of these cytokines,
      as well as iNOS and COX-2. The results of this study suggested that KME has anti
      inflammatory effects on DSS-induced UC in mice (C57BL/6J strain) by reducing the
      colonic levels and inhibiting the mRNA expression of pro-inflammatory cytokines.

PMID- 23969783
TI  - The misoprostol vaginal insert: deja vu all over again.

PMID- 23969784
TI  - Expanding the screening for diabetes in pregnancy: overmedicalization or the
      right thing to do?

PMID- 23969785
TI  - Enhancing the needle count in the haystack: serial ultrasonography for low-to
      moderate risk adnexal masses.

PMID- 23969786
TI  - Frequency and disposition of ovarian abnormalities followed with serial
      transvaginal ultrasonography.
AB  - OBJECTIVE: To examine the prevalence, incidence, persistence, and resolution of
      ovarian abnormalities using serial transvaginal ultrasonography. METHODS: A group
      of 39,337 women in the University of Kentucky Ovarian Cancer Screening Program
      were monitored with 221,576 baseline and interval transvaginal ultrasonography.
      RESULTS: The transvaginal ultrasonogram was normal for first and all subsequent
      visits for 31,834 participants (80.9%), whereas 6,807 women (17.3%) had
      transvaginal ultrasonograms interpreted as abnormal and were monitored over
      21,588 ultrasonograms. Ovarian cysts were more common in premenopausal
      (prevalence 34.9%, incidence 15.3%) than in postmenopausal women (prevalence
      17.0%, incidence 8.2%). For the group with abnormalities, the initial
      transvaginal ultrasonogram was abnormal in 46.7% of the cases, of which 63.2%
      resolved to normal on subsequent ultrasonograms. Of 35,314 cases classified as
      normal on the first examination, 9.9% were abnormal on subsequent annual
      examinations. The abnormal findings were classified as follows: unilocular cysts
      (11.5%), cysts with septations (9.8%), cysts with solid areas (7.1%), and solid
      masses (1.8%). Many transvaginal ultrasonographic abnormalities were followed to
      resolution. Surgery was performed on 557 participants for 85 ovarian malignancies
      and 472 nonmalignancies. Over the duration of the study, the positive predictive
      value (PPV) increased from 8.1% to 24.7%. CONCLUSION: Serial ultrasonography has
      shown that many ovarian abnormalities resolve, even if the initial appearance is
      complex, solid, or bilateral. Thus, it is advantageous to avoid a single
      transvaginal ultrasonographic abnormality as the sole trigger for surgery and to
      take a measured serial approach to reduce false-positive results and increase the
      PPV. LEVEL OF EVIDENCE: II.

PMID- 23969787
TI  - Risk factors for anal intraepithelial neoplasia in women with genital dysplasia.
AB  - OBJECTIVE: To identify risk factors associated with anal intraepithelial
      neoplasia and develop a model for predicting the likelihood of anal
      intraepithelial neoplasia in heterosexual women. METHODS: A prospective cohort of
      327 patients from 2006 to 2011 with a biopsy-confirmed diagnosis of genital
      intraepithelial neoplasia (vulvar, vaginal, or cervical) underwent both anal
      cytology and anoscopy. Variables significant between those with and without anal
      intraepithelial neoplasia were identified using logistic regression. A forward
      stepwise regression analysis was carried out to identify a combination of
      variables that effectively predicted anal intraepithelial neoplasia. RESULTS: In
      the cohort of analyzed patients, 64 (46.7%) women with anal intraepithelial
      neoplasia were identified, yielding a prevalence of 19.6%. Immunosuppression,
      vulvar dysplasia, multiple sexual partners (more than four), smoking history, and
      history of anal sex were positively associated with anal intraepithelial
      neoplasia (P<.05). These variables were analyzed using forward stepwise logistic
      regression. The final model used the presence of any two of three risk factors
      (vulvar intraepithelial neoplasia [VIN], immunosuppression, and history of anal
      sex) to predict 38.8% of anal intraepithelial neoplasia in our population. Area
      under the receiver operating characteristic curve for two of three of the factors
      was 0.708 (P<.05). This model has a negative predictive value of 88.2% (95%
      confidence interval [CI] 0.83-0.92) and positive predictive value of 43.1% (95%
      CI 0.31-0.56). CONCLUSION: A simple predictive model based on the presence or
      absence of two of three risk factors (VIN, immunosuppression, and history of anal
      sex) can be used by the clinician to quantify anal intraepithelial neoplasia risk
      in women with genital dysplasia. LEVEL OF EVIDENCE: II.

PMID- 23969788
TI  - Survival in women with grade 1 serous ovarian carcinoma.
AB  - OBJECTIVE: To examine clinicopathologic variables associated with survival among
      women with low-grade (grade 1) serous ovarian carcinoma enrolled in a phase III
      study. METHODS: This was an ancillary data analysis of Gynecologic Oncology Group
      protocol 182, a phase III study of women with stage III-IV epithelial ovarian
      carcinoma treated with carboplatin and paclitaxel compared with triplet or
      sequential doublet regimens. Women with grade 1 serous carcinoma (a surrogate for
      low-grade serous disease) were included in the analysis. RESULTS: Among the 3,686
      enrolled participants, 189 had grade 1 disease. The median age was 56.5 years and
      87.3% had stage III disease. The median follow-up time was 47.1 months.
      Stratification according to residual disease after primary surgery was
      microscopic residual in 24.9%, 0.1-1.0 cm of residual in 51.3%, and more than 1.0
      cm of residual in 23.8%. On multivariate analysis, only residual disease status
      (P=.006) was significantly associated with survival. Patients with microscopic
      residual had a significantly longer median progression-free (33.2 months) and
      overall survival (96.9 months) compared with those with residual 0.1-1.0 cm (14.7
      months and 44.5 months, respectively) and more than 1.0 cm of residual disease
      (14.1 months and 42.0 months, respectively; progression-free and overall
      survival, P<.001). After adjustment for other variables, patients with low-grade
      serous carcinoma with measurable residual disease had a similar adjusted hazard
      ratio for death (2.12; P=.002) as their high-grade serous carcinoma counterparts
      with measurable disease (2.31; P<.001). CONCLUSIONS: Surgical cytoreduction to
      microscopic residual was associated with improved progression-free and overall
      survival in women with advanced-stage low-grade serous ovarian carcinoma.
      CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov,
      NCT00011986. LEVEL OF EVIDENCE: II.

PMID- 23969789
TI  - Nationwide trends in the performance of inpatient hysterectomy in the United
      States.
AB  - OBJECTIVE: To examine the use of inpatient hysterectomy and explore changes in
      the use of various routes of hysterectomy and patterns of referral. METHODS: The
      Nationwide Inpatient Sample was used to identify all women aged 18 years or older
      who underwent inpatient hysterectomy between 1998 and 2010. Weighted estimates of
      national trends were calculated and the number of procedures performed estimated.
      Trends in hospital volume and across hospital characteristics were examined.
      RESULTS: After weighting, we identified a total 7,438,452 women who underwent
      inpatient hysterectomy between 1998 and 2010. The number of hysterectomies
      performed annually rose from 543,812 in 1998 to a peak of 681,234 in 2002; it
      then declined consistently annually and reached 433,621 cases in 2010. Overall,
      247,973 (36.4%) fewer hysterectomies were performed in 2010 compared with 2002.
      From 2002 to 2010 the number of hysterectomies performed for each of the
      following indications declined: leiomyoma (-47.6%), abnormal bleeding (-28.9%),
      benign ovarian mass (-63.1%), endometriosis (-65.3%), and pelvic organ prolapse (
      39.4%). The median hospital case volume decreased from 83 procedures per year in
      2002 to 50 cases per year in 2010 (P<.001). CONCLUSION: The number of inpatient
      hysterectomies performed in the United States has declined substantially over the
      past decade. The median number of hysterectomies per hospital has declined
      likewise by more than 40%. LEVEL OF EVIDENCE: III.

PMID- 23969790
TI  - Diminishing availability of trial of labor after cesarean delivery in New Mexico
      hospitals.
AB  - OBJECTIVE: To examine the availability of trial of labor after cesarean delivery
      (TOLAC) in New Mexico from 1998 to 2012 and maternity care providers' perception
      of barriers to TOLAC. METHODS: Hospital maternity unit directors were surveyed
      regarding TOLAC availability from 1998 to 2012. Maternity care providers
      (obstetrician-gynecologists, certified nurse-midwives, and family medicine
      physicians) were surveyed in 2008 regarding resources and barriers to providing
      TOLAC and emergency cesarean delivery. RESULTS: Trial of labor after cesarean
      delivery was available in 100% of counties with maternity care units in 1998
      (22/22); by 2008, availability decreased to 32% (7/22). After changes in national
      guidelines, availability increased slightly to 9 of 22 (41%) in 2012. Barriers to
      TOLAC included anesthesia availability (88%), hospital and medical malpractice
      policies (80%), malpractice cost (69%), and obstetric surgeon availability (59%).
      In hospitals without TOLAC services, 73% of maternity care providers indicated a
      surgeon could be present in the hospital within 20 minutes of the emergency
      delivery decision; only 43% indicated obstetric anesthesia personnel could be
      present within 20 minutes (P<.001). CONCLUSIONS: Availability of TOLAC in New
      Mexico has decreased dramatically. Policy changes are needed to support TOLAC
      access in rural and community hospitals. LEVEL OF EVIDENCE: III.

PMID- 23969791
TI  - The role of growth trajectories in classifying fetal growth restriction.
AB  - OBJECTIVE: To examine the validity of a growth trajectory method to discriminate
      between pathologically and constitutionally undergrown fetuses using repeated
      measures of estimated fetal weight. METHODS: In a prospective, observational,
      multicenter study in Ireland, 1,116 women with a growth-restricted fetus
      diagnosed participated with the objective of evaluating ultrasound findings as
      predictors of pediatric morbidity and mortality. Fetal growth trajectories were
      based on estimated fetal weight. RESULTS: Between 22 weeks of gestation and term,
      two fetal growth trajectories were identified: normal (96.7%) and pathologic
      (3.3%). Compared with the normal trajectory, the pathologic trajectory was
      associated with an increased risk for preeclampsia (odds ratio [OR] 8.1, 95%
      confidence interval [CI] 2.6-23.4), increased umbilical artery resistance at 30
      weeks of gestation (OR 12.6, 95% CI 4.6-34.1) or 34 weeks of gestation (OR 28.0,
      95% CI 8.9-87.7), reduced middle cerebral artery resistance at 30 weeks of
      gestation (OR 0.33, 95% CI 0.12-0.96) or 34 weeks of gestation (OR 0.14, 95% CI
      0.03-0.74), lower gestational age at delivery (mean 32.02 weeks of gestation
      compared with 38.02 weeks of gestation; P<.001), and higher perinatal
      complications (OR 21.5, 95% CI 10.5-44.2). In addition, 89.2% of newborns with
      pathologic fetal growth were admitted to neonatal intensive care units compared
      with 25.9% of those with normal growth. CONCLUSIONS: Fetal growth trajectory
      analysis reliably differentiated fetuses with a pathologic growth pattern among a
      group of women with growth-restricted fetuses. With further development, this
      approach could provide clarity to how we define, identify, and ultimately manage
      pathologic fetal growth. LEVEL OF EVIDENCE: II.

PMID- 23969792
TI  - Timing of excessive pregnancy-related weight gain and offspring adiposity at
      birth.
AB  - OBJECTIVE: To evaluate whether the timing of excessive maternal weight gain in a
      cohort of women following current guidelines for healthy living during pregnancy
      affects neonatal adiposity at birth. METHODS: One hundred seventy-two healthy
      women who were at least 18 years old with body mass indexes (BMIs) of at least
      18.5 were recruited between 16 weeks and 20 weeks of gestation. The cohort
      followed healthy living guidelines during pregnancy and were retrospectively
      grouped according to 2009 Institute of Medicine guidelines for weight gain in the
      first and second halves of pregnancy: 1) appropriate gestational weight gain (ie,
      within Institute of Medicine recommendations) in the first and second halves of
      pregnancy ("overall appropriate"); 2) appropriate gestational weight gain in the
      first half of pregnancy and excessive gestational weight gain in the second half
      of pregnancy ("late excessive"); 3) excessive gestational weight gain in the
      first half of pregnancy and appropriate gestational weight gain in the second
      half of pregnancy ("early excessive"); and 4) excessive gestational weight gain
      throughout pregnancy ("overall excessive"). Primary measures included neonatal
      weight, length, BMI, and body fat at birth measured 6-18 hours after delivery.
      Neonatal body fat greater than 14% was considered excessive. RESULTS: Neonates of
      women who gained excessively in the first half of pregnancy exhibited greater
      heel-crown length, birth weight, and excessive body fat ("early excessive" 17.5+/
      3.1%, "overall excessive" 18.7+/-3.3%) compared with those born to women who
      gained appropriately ("overall appropriate" 13.2+/-4.1%; "late excessive" 14.7+/
      3.3%; P<.01). Neonates of women who gained excessively in the first half of
      pregnancy had an increased risk (odds ratio [OR] 2.64, 95% confidence interval
      [CI] 1.35-5.17) of elevated body fat at birth compared with neonates of women
      with total excessive weight gain (OR 1.49, 95% CI 0.80-2.79). CONCLUSION: Timing
      of excessive weight gain is an important factor influencing neonatal
      morphometrics. Prevention of early excessive weight gain should be encouraged in
      the period before conception and reinforced early in pregnancy. LEVEL OF
      EVIDENCE: II.

PMID- 23969793
TI  - The association of maternal obesity with fetal pH and base deficit at cesarean
      delivery.
AB  - OBJECTIVE: To evaluate the association between maternal body mass index (BMI) and
      umbilical cord acid-base status at the time of cesarean delivery. METHODS: We
      conducted a retrospective multicenter cohort study using data from the Cesarean
      Section Registry of the Eunice Kennedy Shriver National Institute of Child Health
      and Human Development Maternal-Fetal Medicine Units Network. Women were included
      if they delivered a live, nonanomalous singleton at 37-41 weeks of gestation by
      prelabor cesarean under spinal anesthesia. We excluded women with diagnoses that
      might be associated with uteroplacental insufficiency. Body mass index at
      delivery was examined both as a continuous and categorical exposure, and acid
      base status was based on cord arterial pH and base deficit. RESULTS: There were
      5,742 mother-neonate pairs who met criteria for analysis. Among possible
      confounders (including sociodemographic variables, number of previous uterine
      incisions, diabetes, hematocrit, neonatal gender, and birth weight), African
      American race, birth weight, parity, and smoking status were significantly
      associated with both BMI and acid-base parameters. Adjusted for those four
      factors, with increasing BMI category (less than 25, 25-29.9, 30-34.9, 35-39.9,
      and 40 or higher), mean pH decreased from 7.25 to 7.22 (P<.001), proportion with
      pH less than 7.1 increased from 3.5% to 7.7% (P=.011), mean base deficit
      increased from 4.01 mmol/L to 4.83 mmol/L (P=.030), and proportion with base
      deficit of 12 mmol/L or more increased from 0.6% to 4.7% (P=.003). When BMI was
      analyzed continuously and adjusted for these confounders, for every 10-unit
      increase in BMI, cord arterial pH decreased by 0.01 (P<.001) and base deficit
      increased by 0.26 mmol/L (P=.005). CONCLUSION: For women undergoing nonemergent
      prelabor cesarean delivery under spinal anesthesia, fetal pH declines and base
      deficit rises as maternal BMI increases. LEVEL OF EVIDENCE: II.

PMID- 23969794
TI  - Increased prevalence of major congenital anomalies in births with placental
      abruption.
AB  - OBJECTIVE: To examine the association between major congenital anomalies and
      placental abruption. METHODS: A register-based retrospective case-control study
      was carried out from 1987 to 2005. Data on baseline characteristics and birth
      outcomes were collected from three Finnish national health registers: the Medical
      Birth Register, National Hospital Discharge Register, and Register of Congenital
      Malformations. The study population consisted of 4,190 women with singleton birth
      and placental abruption. Three control women without placental abruption were
      selected for each case, matched by maternal age, parity, year of birth, and
      hospital district. The main outcome measure of the study was a major congenital
      anomaly associated with placental abruption. RESULTS: In total, 261 (prevalence
      623/10,000) births with placental abruption and 415 (prevalence 330/10,000)
      control births had major congenital anomalies (odds ratio [OR] 1.92, 95%
      confidence interval [CI] 1.6-2.52). The association was strongest among births
      with growth restriction and prematurity. Adjusted analysis revealed a significant
      association with central nervous system anomalies (OR 2.33, 95% CI 1.29-4.23),
      anomalies of the eyes and ears (OR 1.82, 95% CI 1.08-3.09), cardiovascular
      anomalies (OR 1.78, 95% CI 1.34-2.37), respiratory anomalies (OR 3.51, 95% CI
      1.56-7.90), gastrointestinal anomalies (OR 3.81, 95% CI 2.27-6.41), genitourinary
      anomalies (OR 2.55, 95% CI 1.73- 3.74), musculoskeletal anomalies (OR 1.67, 95%
      CI 1.24-2.24), and anomalies of integument (OR 3.29, 95% CI 1.20-8.98) in births
      complicated by placental abruption. CONCLUSIONS: Major congenital anomalies are
      twice as common among neonates born from pregnancies complicated by placental
      abruption compared with control pregnancies without abruption. This observation
      applies to several organ systems. LEVEL OF EVIDENCE: II.

PMID- 23969795
TI  - Prevalence and correlates of gastroschisis in 15 states, 1995 to 2005.
AB  - OBJECTIVE: To identify trends in the prevalence and epidemiologic correlates of
      gastroschisis using a large population-based sample with cases identified by the
      National Birth Defects Prevention Network over the course of an 11-year period.
      METHODS: This study examined 4,713 cases of gastroschisis occurring in 15 states
      during 1995-2005, using public use natality data sets for denominators.
      Multivariable Poisson regression was used to identify statistically significant
      risk factors, and Joinpoint regression analyses were conducted to assess temporal
      trends in gastroschisis prevalence by maternal age and race and ethnicity.
      RESULTS: Results show an increasing temporal trend for gastroschisis (from 2.32
      per 10,000 to 4.42 per 10,000 live births). Increasing prevalence of
      gastroschisis has occurred primarily among younger mothers (11.45 per 10,000 live
      births among mothers younger than age 20 years compared with 5.35 per 10,000
      among women aged 20 to 24 years). In the multivariable analysis, using non
      Hispanic whites as the referent group, non-Hispanic black women had the lowest
      risk of having a gastroschisis-affected pregnancy (prevalence ratio 0.42, 95%
      confidence interval [CI] 0.37-0.48), followed by Hispanics (prevalence ratio
      0.86, 95% CI 0.81-0.92). Gastroschisis prevalence did not differ by newborn sex.
      CONCLUSIONS: Our findings demonstrate that the prevalence of gastroschisis has
      been increasing since 1995 among 15 states in the United States, and that higher
      rates of gastroschisis are associated with non-Hispanic white maternal race and
      ethnicity, and maternal age younger than 25 years (particularly younger than 20
      years of age). LEVEL OF EVIDENCE: III.

PMID- 23969796
TI  - Biomarkers and cervical length to predict spontaneous preterm birth in
      asymptomatic high-risk women.
AB  - OBJECTIVE: To investigate whether biomarkers from different pathways of
      spontaneous preterm birth (cervical membrane degradation [fetal fibronectin],
      cervical remodeling [soluble E-cadherin], and inflammation (elafin, surfactant
      protein-D, interleukin-6 [IL-6]) were superior to one biomarker alone in
      predicting preterm birth. Our secondary objective was to examine the association
      of these biomarkers with cervical length in predicting preterm birth. METHODS: We
      performed a single-center, prospective cohort study from August 2011 to November
      2012 of asymptomatic women at risk for spontaneous preterm birth as a result of
      obstetric and gynecologic history. Cervicovaginal fluid and cervical length
      measurements were collected at two time points (20-23 6/7 weeks and 24-27 6/7
      weeks of gestation). RESULTS: Among the 104 women with complete data, the preterm
      birth rate was 24.5%. Prior preterm birth (P=.006) and cervical length at visit 1
      (P=.003) were significantly associated with preterm birth, whereas fetal
      fibronectin and median biomarker levels (elafin, soluble E-cadherin, IL-6) were
      not. Median surfactant protein-D levels at visit 1 by preterm birth status were
      statistically but not clinically different (0.44 ng/mL compared with 0.40 ng/mL,
      P<.001). Analyses of biomarkers from more than one pathway were not superior to
      single biomarker analyses in predicting prematurity. Neither inclusion of
      biomarkers nor fetal fibronectin improved the predictive ability of cervical
      length alone. CONCLUSION: Cervical length assessment and obstetric history but
      not fetal fibronectin or biomarkers were useful in the risk stratification of
      women identified to be at greatest risk for spontaneous preterm birth. LEVEL OF
      EVIDENCE: II.

PMID- 23969797
TI  - Uterine massage to reduce blood loss after vaginal delivery: a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate whether sustained transabdominal uterine massage can
      reduce blood loss after vaginal delivery. METHODS: In this multicenter randomized
      controlled trial, eligible women who had delivered vaginally were randomly
      assigned to receive 10 units oxytocin intramuscularly immediately after delivery
      of the shoulder plus 30 minutes of sustained transabdominal uterine massage after
      delivery of the placenta or to 10 units oxytocin intramuscularly alone. The
      primary outcome was blood loss of 400 mL or more in the 2 hours after delivery of
      the neonate. Secondary outcomes included blood loss of 1,000 mL or more, blood
      loss in the 2 hours after delivery, use of therapeutic uterotonics or other
      hemostatic procedures, hemoglobin of lower than 80 g/L before discharge, and need
      for blood transfusion. Analysis was by intent to treat. With a one-sided alpha of
      0.05 and a power of 0.8, a sample size of 1,061 women per group was calculated to
      detect a 3% absolute decrease in the primary outcome. RESULTS: Of 2,340 eligible
      women, 1,170 were randomized to oxytocin plus uterine massage and 1,170 to the
      oxytocin-only group. Baseline characteristics were similar in both groups. The
      incidence of blood loss of 400 mL or more in the 2 hours after delivery was not
      significantly different between the two groups (143/1,170 [12.2%] compared with
      144/1,170 [12.3%]; relative risk 0.99, 95% confidence interval 0.88-1.13)
      according to intent-to-treat analysis with a power of more than 0.8. No
      significant differences were found in the secondary outcomes. CONCLUSION: In
      patients delivered vaginally, transabdominal uterine massage after delivery of
      the placenta in addition to oxytocin does not reduce blood loss when compared
      with administration of oxytocin alone. CLINICAL TRIAL REGISTRATION: Chinese
      Clinical Trial Registry, www.chictr.org, ChiCTR-TRC-11001763. LEVEL OF EVIDENCE:
      I.

PMID- 23969798
TI  - Postpartum contraception in publicly-funded programs and interpregnancy
      intervals.
AB  - OBJECTIVE: To assess the extent to which women received contraceptive services
      within 90 days after birth at their first or subsequent visits and whether
      contraceptive provision was associated with optimal interpregnancy intervals.
      METHOD: We linked California's 2008 Birth Statistical Master File with Medicaid
      databases to build a cohort of women aged 15-44 years who had given birth in 2008
      and received publicly-funded health care services in the 18 months after their
      previous live birth (N=117,644). We determined whether provision of contraception
      within 90 days after birth was associated with optimal interpregnancy intervals
      when controlling for covariates. RESULT: Only 41% (n=48,775) of women had a
      contraceptive claim within 90 days after birth. To avoid short interpregnancy
      intervals, 6 women would need to receive contraception to avoid one additional
      short interval (number needed to treat=6.38). Receipt of a contraceptive method,
      receiving contraception at the first clinic visit, and being seen by Medi-Cal and
      its family planning expansion program were significantly associated with
      avoidance of short interpregnancy intervals. Receiving contraception at the first
      postpartum clinic visit had an additional independent effect on avoiding short
      interpregnancy intervals when controlling for the other variables. Although
      foreign-born women had 47% higher odds of avoiding short interpregnancy intervals
      than U.S.-born women, women of Asian and Pacific Islander ethnicity had 24% lower
      odds of avoiding short interpregnancy intervals than white women. CONCLUSION:
      Findings of this study suggest that closer attention to provision of postpartum
      contraception in publicly-funded programs has the potential to improve optimal
      interpregnancy intervals among low-income women. LEVEL OF EVIDENCE: II.

PMID- 23969799
TI  - Sterilization of rural and urban women in the United States.
AB  - OBJECTIVE: To examine the prevalence of sterilization among women aged 20-34
      years in rural and urban areas in the United States. METHODS: Data were obtained
      from the 2006-2010 National Survey of Family Growth, a cross-sectional survey
      conducted by the Centers for Disease Control and Prevention. The study population
      included the 4,685 female respondents who did not want to become pregnant at the
      time of the survey. Women who were not sexually active with men or were infertile
      for reasons other than contraception were excluded. We performed bivariate and
      stratified analysis and multivariable logistic regression modeling to determine
      the associations between place of residence and sterilization after considering
      other demographic characteristics. RESULTS: Rural women were at increased odds of
      undergoing sterilization compared with urban and suburban women (22.75% compared
      with 12.69%, respectively; crude odds ratio [OR] 2.03, 95% confidence interval
      [CI] 1.44-2.86; risk difference 0.10, 95% CI 0.05-0.16). Education level was
      found to be a significant effect modifier of the relationship between location of
      residence and sterilization. In adjusted analysis, controlling for age, parity,
      race and ethnicity, income, insurance status, history of unintended pregnancy,
      and relationship status, rural women without a high school degree were more
      likely to have undergone sterilization compared with urban and rural women with
      greater than a high school education (OR 8.34, 95% CI 4.45-15.61). CONCLUSIONS:
      Rural women with low education levels have a high prevalence of sterilization.
      Future studies need to address the reasons for this interaction between education
      and geography and its influence on contraceptive method choice. LEVEL OF
      EVIDENCE: II.

PMID- 23969800
TI  - Presenting symptoms of women with depression in an obstetrics and gynecology
      setting.
AB  - OBJECTIVE: To describe the presenting symptoms of women with depression in two
      obstetrics and gynecology clinics, determine depression diagnosis frequency, and
      examine factors associated with depression diagnosis. METHODS: Data were
      extracted from charts of women screening positive for depression in a clinical
      trial testing a collaborative care depression intervention. Bivariate and
      multivariable analyses examined patient factors associated with the diagnosis of
      depression by an obstetrician-gynecologist (ob-gyn). RESULTS: Eleven percent of
      women with depression presented with a psychologic chief complaint but another
      30% mentioned psychologic distress. All others noted physical symptoms only or
      presented for preventive care. Ob-gyns did not identify 60% of women with a
      depression diagnosis. Depression severity was similar in women who were or were
      not diagnosed by their ob-gyns. Bivariate analyses showed four factors
      significantly associated with depression diagnosis: reporting a psychologic
      symptom as the chief complaint or associated symptom (72% compared with 18.6%,
      P<.001), younger age (35.5 years compared with 40.8 years, P<.005), being within
      12 months postpartum (13.9% compared with 2.8%, P<.005), and a primary care
      oriented visit (72% compared with 30%, P<.001). Multivariable analysis showed
      that reporting a psychologic symptom (adjusted odds ratio [OR] 8.90, 95%
      confidence interval [CI] 4.15-19.10, P<.001), a primary care oriented visit
      (adjusted OR 2.46, 95% CI 1.14-5.29, P=.03), and each year of increasing age
      (adjusted OR 0.96, 95% CI 0.93-0.96, P=.02) were significantly associated with a
      depression diagnosis. CONCLUSION: The majority of women with depression presented
      with physical symptoms; most women with depression were not diagnosed by their ob
      gyn, and depression severity was similar in those diagnosed and those not
      diagnosed. LEVEL OF EVIDENCE: III.

PMID- 23969802
TI  - Ultrasonographic evaluation of pelvic organ support during pregnancy.
AB  - OBJECTIVE: To investigate whether pregnancy affects levator hiatus dimensions and
      the position and mobility of the bladder neck and the levator ani muscle in
      nulliparous pregnant women. METHODS: In the present study, 274 nulliparous
      pregnant women were examined at 21 weeks and 37 weeks of gestation using three
      dimensional and four-dimensional transperineal ultrasonography at rest, during
      contraction, and during Valsalva maneuver. Levator hiatus dimensions were the
      anteroposterior diameter, the transverse diameter, and the area measured in
      rendered images. Positions of the bladder neck and levator plate were analyzed in
      the midsagittal plane, and mobility was calculated as displacement of the bladder
      neck or levator plate from rest to contraction or from rest to Valsalva. RESULTS:
      A significant increase for all levator hiatus dimension measurements was found
      from 21 weeks to 37 weeks of gestation. The most marked change was found for
      levator hiatus area at rest and during Valsalva maneuver, in which the mean area
      was increased by 17.1% (11.7-13.7 cm(2)) and 21.4% (15.4-18.7 cm(2)),
      respectively. Bladder neck mobility changed significantly during pregnancy. The
      most marked change was seen from rest to contraction (mean -14 mm, standard
      deviation 0.4). CONCLUSIONS: An increase of all hiatal dimensions as well as
      bladder neck mobility was found from 21 weeks to 37 weeks of gestation in
      nulliparous pregnant women. The findings indicate that the changes in pelvic
      organ support are not solely caused by delivery, but also by physiologic changes
      during pregnancy. LEVEL OF EVIDENCE: II.

PMID- 23969801
TI  - Enhanced recovery in gynecologic surgery.
AB  - OBJECTIVE: To investigate the effects of enhanced recovery (a multimodal
      perioperative care enhancement protocol) in patients undergoing gynecologic
      surgery. METHODS: Consecutive patients managed under an enhanced recovery pathway
      and undergoing cytoreduction, surgical staging, or pelvic organ prolapse surgery
      between June 20, 2011, and December 20, 2011, were compared with consecutive
      historical controls (March to December 2010) matched by procedure. Wilcoxon rank
      sum, chi, and Fisher's exact tests were used for comparisons. Direct medical
      costs incurred in the first 30 days were obtained from the Olmsted County
      Healthcare Expenditure and Utilization Database and standardized to 2011 Medicare
      dollars. RESULTS: A total of 241 enhanced recovery women in the case group (81
      cytoreduction, 84 staging, and 76 vaginal surgery) were compared with women in
      the control groups. In the cytoreductive group, patient-controlled anesthesia use
      decreased from 98.7% to 33.3% and overall opioid use decreased by 80% in the
      first 48 hours with no change in pain scores. Enhanced recovery resulted in a 4
      day reduction in hospital stay with stable readmission rates (25.9% of women in
      the case group compared with 17.9% of women in the control group) and 30-day cost
      savings of more than $7,600 per patient (18.8% reduction). No differences were
      observed in rate (63% compared with 71.8%) or severity of postoperative
      complications (grade 3 or more: 21% compared with 20.5%). Similar, albeit less
      dramatic, improvements were observed in the other two cohorts. Ninety-five
      percent of patients rated satisfaction with perioperative care as excellent or
      very good. CONCLUSIONS: Implementation of enhanced recovery was associated with
      acceptable pain management with reduced opioids, reduced length of stay with
      stable readmission and morbidity rates, good patient satisfaction, and
      substantial cost reductions. LEVEL OF EVIDENCE: II.

PMID- 23969803
TI  - Predicting the decline in human chorionic gonadotropin in a resolving pregnancy
      of unknown location.
AB  - OBJECTIVES: To characterize the curve derived from serial human chorionic
      gonadotropin (hCG) values in women with spontaneous resolution of pregnancy of
      unknown location and to assess factors that modify the decline. METHODS: Data
      from three sites were extracted from a clinical database of women with a
      symptomatic pregnancy of unknown location that required follow-up with serial hCG
      levels. A nonlinear mixed-effects regression model was used to generate hCG
      elimination curves. RESULTS: Four hundred forty-three women presenting with a
      pregnancy of unknown location that resolved without intervention were studied
      between September 2007 and May 2009. Women older than 35 years had a slower hCG
      decline (P=.001) and those with pain had a steeper decline (P=.006), but these
      changes did not alter the curve in a clinically meaningful way. The decline in
      hCG is faster for those with a higher level at presentation. The average decline
      of hCG in women with spontaneous resolution is slower than previously reported.
      However, the minimal decline in hCG for women with spontaneous resolution of a
      pregnancy of unknown location ranged from 35% to 50% at 2 days of follow-up and
      from 66% to 87% at 7 days, which is more rapid than previously reported.
      CONCLUSION: In a diverse population, using updated statistical methods, it was
      observed that the minimal decline in hCG for women with spontaneous resolution is
      more rapid than previously reported. A decline slower than these thresholds may
      indicate the presence of retained trophoblastic tissue or ectopic pregnancy.
      LEVEL OF EVIDENCE: III.

PMID- 23969804
TI  - Absence of association between serum folate and preeclampsia in women exposed to
      food fortification.
AB  - OBJECTIVE: To evaluate serum folate concentration early in pregnancy and any
      association with hypertensive disorders of pregnancy in a population exposed to
      folic acid supplementation and food fortification. METHODS: This is a nested case
      control study based on a prospective cohort of 7,929 pregnant women recruited in
      the Quebec City metropolitan area, including 214 participants who developed a
      hypertensive disorder of pregnancy and 428 normotensive participants in the
      control group matched for parity, multiple pregnancy, smoking status,
      gestational, and maternal age at inclusion, and duration of blood sample storage.
      Serum folate levels were measured at a mean of 14 weeks of gestation. RESULTS:
      More than 98% of the participants took folic acid or multivitamins before the end
      of the first trimester. Mean serum folate levels were accordingly high and there
      were no differences between women who further developed a hypertensive disorder
      of pregnancy compared with women in the control group (60.1 nmol/L compared with
      57.9 nmol/L; P=.51). The proportion of participants with serum folate below the
      10th percentile (less than 22.3 nmol/L) of age-matched women in our outpatient
      population was similar between groups (P=.66) and no participant had levels
      generally defined as folate deficiency (less than 10 nmol/L). CONCLUSION: In a
      general cohort of pregnant women benefiting from a national policy of folic acid
      food fortification combined with a high adherence to folic acid supplementation,
      serum folate levels are high and do not differ between women who develop a
      hypertensive disorder of pregnancy and women who remain normotensive. Further
      supplementation with higher doses is unlikely to be beneficial in such
      populations. LEVEL OF EVIDENCE: II.

PMID- 23969806
TI  - National Institutes of Health consensus development conference statement:
      diagnosing gestational diabetes mellitus, March 4-6, 2013.

PMID- 23969805
TI  - Vasa previa: clinical presentations, outcomes, and implications for management.
AB  - OBJECTIVE: To review experience with diagnosis, clinical associations, and
      outcomes of vasa previa in a single institution. METHODS: This was a
      retrospective review of all identified vasa previa cases from January 1 1990, to
      June 30, 2010. RESULTS: Sixty cases of vasa previa were identified (53
      singletons, seven twins); 56 cases were diagnosed before delivery. An abnormal
      cord insertion or abnormal placental location was present in 55 cases. Missed
      diagnoses were attributed to technical and observer factors. Preterm bleeding was
      encountered in 25 (42%) case group participants. Seven case group participants
      required an emergent delivery, with significant neonatal morbidity and mortality.
      Twin pregnancies had a significantly earlier median age at delivery of 32 weeks
      of gestation compared with 35 weeks of gestations in singletons (P=.01). The
      seven twin pregnancies had a 28.6% emergent preterm delivery rate, whereas
      singletons had a 4.1% rate (P=.07). In 14 case group participants, the membranous
      fetal vessel was located in the lower uterus and not directly over the cervix.
      The vessel location was not related to the risk of emergent delivery. CONCLUSION:
      Transvaginal ultrasound scans of at-risk patients can identify most cases of vasa
      previa. Preterm bleeding does not usually require immediate delivery. The rate of
      emergent preterm delivery was low in singleton pregnancies. Twins were delivered,
      on average, 3 weeks earlier than singletons. LEVEL OF EVIDENCE: III.

PMID- 23969807
TI  - Pertussis, a disease whose time has come: what can be done to control the
      problem?
AB  - In the United States, major epidemics of pertussis or whooping cough have
      occurred in the last 5 years making this disease a major public health issue. The
      adolescent and adult populations are the major transmitters of disease to the
      community. However, these epidemics have had the greatest effect on the young
      infant population resulting in high rates of hospitalizations and complications
      and accounting for 100% of the mortality. Optimization of vaccine recommendations
      is a strategy that is critically important as a method to control the disease
      burden and decrease the transmission of disease to the young infant population.
      Immunization that is focused on the close contacts of these young infants (the
      cocoon strategy) is felt to be one of the main cornerstones to vaccine
      optimization with the immunization of pregnant women being critical. Transmission
      studies have shown that adolescent and adult close contacts, especially new
      mothers, are the source of disease transmission to their young infants in more
      than 50% of the cases. The Centers for Disease Control and Prevention and the
      American College of Obstetricians and Gynecologists strongly recommend that the
      tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis booster
      vaccine be given to pregnant women during each pregnancy between 27 weeks and 36
      weeks of gestation to protect their infant against pertussis disease. 

PMID- 23969808
TI  - Decreasing prematurity in twin gestations: predicaments and possibilities.
AB  - The twin birth rate has been steadily increasing in the United States over the
      past 10 years attributable in large part to the increased use of reproductive
      technologies. Despite advancements in the prevention of preterm labor for
      singletons, the overall rate of preterm birth has decreased only minimally.
      Several interventions to prevent preterm birth in twins have been studied, but
      none has proven effective. Inpatient bedrest has not been shown to be effective
      and can cause significant maternal morbidity. Although intramuscular 17alpha
      hydroxyprogesterone caproate is effective in decreasing the risk of recurrent
      preterm delivery in singletons, neither it nor cerclage is effective in twin
      gestations, even in those with a short cervix. However, small trials, subgroup
      analyses, and a meta-analysis suggest that vaginal progesterone and the Arabin
      cervical pessary may reduce rates of preterm birth in twins of mothers with a
      short cervix. Given the current lack of effective therapies to prevent preterm
      birth in twins, large multicenter trials are needed to assess the effectiveness
      of vaginal progesterone and pessary in twins of mothers with a short cervix. 

PMID- 23969809
TI  - Risk of acute thromboembolic events with oral contraceptive use: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To estimate the risk of venous thromboembolism, stroke, or myocardial
      infarction (MI) associated with the use of oral contraceptive pills (OCPs) and to
      describe how these risks vary by dose or formulation. DATA SOURCES: We searched
      PubMed, Embase, the Cochrane Database of Systematic Reviews, and
      ClinicalTrials.gov for studies published from January 1995 through June 2012 that
      evaluated the association between OCP use and risk of venous thromboembolism,
      stroke, or MI. METHODS OF STUDY SELECTION: We reviewed 6,476 citations. We
      included English-language, controlled studies with human participants reporting a
      quantitative association between exposure to OCPs and outcomes of venous
      thromboembolism, stroke, or MI. Two investigators independently reviewed articles
      for inclusion or exclusion; discordant decisions were resolved by team review and
      consensus. Random-effects meta-analysis was used to generate summary odds ratios
      (ORs). TABULATION, INTEGRATION, AND RESULTS: Fifty studies met inclusion
      criteria. There were no randomized clinical trials. We found threefold increased
      odds of venous thromboembolism among current compared with noncurrent OCP users
      (14 studies; OR 2.97, 95% confidence interval [CI] 2.46-3.59). We found twofold
      increased odds of ischemic stroke (seven studies; OR 1.90, 95% CI 1.24-2.91).
      There was no evidence of increased risk of hemorrhagic stroke (four studies; OR
      1.03, 95% CI 0.71-1.49) or MI (eight studies; OR 1.34, 95% CI 0.87-2.08).
      CONCLUSION: Current use of combined OCPs is associated with increased odds of
      venous thromboembolism and ischemic stroke but not hemorrhagic stroke or MI.

PMID- 23969810
TI  - What is new in preterm birth prevention? Important recent articles.
AB  - This month, we focus on current research in preterm birth prevention. Dr. Andrews
      discusses recent publications, and each is concluded with a "bottom line" that is
      the take-home message. The complete reference for each can be found in on this
      page, along with direct links to the abstracts. 

PMID- 23969811
TI  - 2012 updated consensus guidelines for the management of abnormal cervical cancer
      screening tests and cancer precursors.

PMID- 23969812
TI  - In reply.

PMID- 23969813
TI  - What is new in gynecologic oncology? Thought-provoking articles from the past
      year.

PMID- 23969814
TI  - In reply.

PMID- 23969815
TI  - Effect of maternal body mass index on serum magnesium levels given for seizure
      prophylaxis.

PMID- 23969816
TI  - In reply.

PMID- 23969817
TI  - Long-term mortality associated with oophorectomy compared with ovarian
      conservation in the Nurses' Health Study.

PMID- 23969818
TI  - In reply.

PMID- 23969819
TI  - Women in leadership positions within obstetrics and gynecology: does the past
      explain the present?

PMID- 23969820
TI  - Reply: To PMID 23168768.

PMID- 23969821
TI  - Ovaries, estrogen, and longevity and long-term mortality associated with
      oophorectomy compared with ovarian conservation in the Nurses' Health Study and
      variation in ovarian conservation in women undergoing hysterectomy for benign
      indications.

PMID- 23969822
TI  - Is breast always best? A personal reflection on the challenges of breastfeeding.

PMID- 23969826
TI  - College publications.

PMID- 23969827
TI  - Practice Bulletin No. 137: Gestational diabetes mellitus.
AB  - Gestational diabetes mellitus (GDM) is one of the most common medical
      complications of pregnancy. Debate continues to surround both the diagnosis and
      treatment of GDM despite several recent large-scale studies addressing these
      issues. The purpose of this document is to 1) provide a brief overview of the
      understanding of GDM, 2) provide management guidelines that have been validated
      by appropriately conducted clinical research, and 3) identify gaps in current
      knowledge toward which future research can be directed. 

PMID- 23969828
TI  - Committee Opinion No. 569: oral health care during pregnancy and through the
      lifespan.
AB  - Oral health is an important component of general health and should be maintained
      during pregnancy and through a woman's lifespan. Maintaining good oral health may
      have a positive effect on cardiovascular disease, diabetes, and other disorders.
      In 2007-2009, 35% of U.S. women reported that they did not have a dental visit
      within the past year and 56% of women did not visit a dentist during pregnancy.
      Access to dental care is directly related to income level; the poorest women are
      least likely to have received dental care. Optimal maternal oral hygiene during
      the perinatal period may decrease the amount of caries-producing oral bacteria
      transmitted to the infant during common parenting behavior, such as sharing
      spoons. Although some studies have shown a possible association between
      periodontal infection and preterm birth, evidence has failed to show any
      improvement in outcomes after dental treatment during pregnancy. Nonetheless,
      these studies did not raise any concern about the safety of dental services
      during pregnancy. To potentiate general health and well-being, women should
      routinely be counseled about the maintenance of good oral health habits
      throughout their lives as well as the safety and importance of oral health care
      during pregnancy.

PMID- 23969829
TI  - Committee Opinion No. 570: breastfeeding in underserved women: increasing
      initiation and continuation of breastfeeding.
AB  - Maternal and infant benefits from breastfeeding are well documented and are
      especially important to underserved women. Underserved women are
      disproportionately likely to experience adverse health outcomes that may improve
      with breastfeeding. They face unique barriers and have low rates of initiation
      and continuation of breastfeeding. Through a multidisciplinary approach that
      involves practitioners, family members, and child care providers, obstetrician
      gynecologists can help underserved women overcome obstacles and obtain the
      benefits of breastfeeding for themselves and their infants. 

PMID- 23969830
TI  - Technology Assessment No. 10: single-incision laparoscopy.
AB  - Single-incision laparoscopy is a minimally invasive technique that decreases the
      number of operative sites used in traditional laparoscopic surgery to one skin
      incision, with the potential advantages of improving cosmesis and decreasing
      postoperative pain. There are limited data to demonstrate the safety and
      feasibility of single-incision surgery. Large prospective studies are needed that
      compare traditional laparoscopy with single-incision laparoscopy for various
      indications. Available evidence demonstrates no distinct clinical advantage of
      single-incision surgery compared with traditional laparoscopy, and issues
      regarding ergonomics, surgeon learning curve, and need for special
      instrumentation still need to be addressed.

PMID- 23969831
TI  - Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and
      regulates network formation.
AB  - Hereditary spastic paraplegias are inherited neurological disorders characterized
      by progressive lower-limb spasticity and weakness. Although more than 50 genetic
      loci are known [spastic gait (SPG)1 to -57], over half of hereditary spastic
      paraplegia cases are caused by pathogenic mutations in four genes encoding
      proteins that function in tubular endoplasmic reticulum (ER) network formation:
      atlastin-1 (SPG3A), spastin (SPG4), reticulon 2 (SPG12), and receptor expression
      enhancing protein 1 (SPG31). Here, we show that the SPG33 protein protrudin
      contains hydrophobic, intramembrane hairpin domains, interacts with tubular ER
      proteins, and functions in ER morphogenesis by regulating the sheet-to-tubule
      balance and possibly the density of tubule interconnections. Protrudin also
      interacts with KIF5 and harbors a Rab-binding domain, a noncanonical FYVE (Fab-1,
      YGL023, Vps27, and EEA1) domain, and a two phenylalanines in an acidic tract
      (FFAT) domain and, thus, may also function in the distribution of ER tubules via
      ER contacts with the plasma membrane or other organelles. 

PMID- 23969832
TI  - Changing the fate of cancer, one splice at a time.

PMID- 23969833
TI  - Microscopy ambient ionization top-down mass spectrometry reveals developmental
      patterning.
AB  - There is immense cellular and molecular heterogeneity in biological systems.
      Here, we demonstrate the utility of integrating an inverted light microscope with
      an ambient ionization source, nanospray electrospray desorption ionization,
      attached to a high-resolution mass spectrometer to characterize the molecular
      composition of mouse spinal cords. We detected a broad range of molecules,
      including peptides and proteins, as well as metabolites such as lipids, sugars,
      and other small molecules, including S-adenosyl methionine and glutathione,
      through top-down MS. Top-down analysis revealed variation in the expression of
      Hb, including the transition from fetal to adult Hb and heterogeneity in Hb
      subunits consistent with the genetic diversity of the mouse models. Similarly,
      temporal changes to actin-sequestering proteins beta-thymosins during development
      were observed. These results demonstrate that interfacing microscopy with ambient
      ionization provides the means to perform targeted in situ ambient top-down mass
      spectral analysis to study the pattern of proteins, lipids, and sugars in
      biologically heterogeneous samples. 

PMID- 23969834
TI  - Alteration of genic 5-hydroxymethylcytosine patterning in olfactory neurons
      correlates with changes in gene expression and cell identity.
AB  - The modified DNA base 5-hydroxymethylcytosine (5hmC) is enriched in neurons where
      it may contribute to gene regulation and cellular identity. To determine how 5hmC
      influences gene expression in an in vivo neuronal population, we assessed the
      patterning and function of the base along the developmental lineage of the main
      olfactory epithelium-from multipotent stem cells through neuronal progenitors to
      mature olfactory sensory neurons (mOSNs). We find that 5hmC increases over gene
      bodies during mOSN development with substantial patterning occuring between the
      progenitor and mOSN stages. Although gene-body 5hmC levels correlate with gene
      expression in all three developmental cell types, this association is
      particularly pronounced within mOSNs. Overexpression of Tet3 in mOSNs markedly
      alters gene-body 5hmC levels and gene expression in a manner consistent with a
      positive role for 5hmC in transcription. Moreover, Tet3 overexpression disrupts
      olfactory receptor expression and the targeting of axons to the olfactory bulb,
      key molecular and anatomical features of the olfactory system. Our results
      suggest a physiologically significant role for gene-body 5hmC in transcriptional
      facilitation and the maintenance of cellular identity independent of its function
      as an intermediate to demethylation.

PMID- 23969835
TI  - Expression of the Arp2/3 complex in human gliomas and its role in the migration
      and invasion of glioma cells.
AB  - A hallmark of directional cell migration is localized actin polymerization at the
      leading protrusions of the cell. The Arp2/3 complex nucleates the formation of
      the dendritic actin network (lamellipodia) at the leading edge of motile cells.
      This study was designed to investigate the role of the Arp2/3 complex in the
      infiltrative behavior of glioma cells. Immunofluorescence and western blotting
      showed a positive correlation between the expression of Arp2/3 and the malignancy
      of glioma specimens (r=0.686, P=0.02) and confocal microscopy demonstrated
      localization of the Arp2/3 complex in lamellipodia of glioma cells. Furthermore,
      we examined the effects of Arp2/3 complex inhibition in U251, LN229 and SNB19
      glioma cells using CK666, an Arp2/3 complex inhibitor. Glioma cells lost
      lamellipodia and cell polarity after treatment with CK666. Inhibition of the
      Arp2/3 complex significantly affected the ability of glioma cells to migrate and
      invade. In the wound-healing assay, CK666 markedly inhibited cell migration, U251
      cell migration was inhibited to 38.73+/-3.45% of control, LN229 cells to 57.40+/
      2.16% of control and SNB19 cells to 34.17+/-3.82% of control. Also, CK666
      significantly impaired Transwell chamber invasion capability of U251, LN229 and
      SNB19 cells compared with DMSO control by 72.70+/-4.86, 39.12+/-8.42 and 41.41+/
      4.66%, respectively. The Arp2/3 complex is, therefore, likely to be a crucial
      participant in glioma cell invasion and migration, and may represent a target for
      therapeutic intervention. 

PMID- 23969838
TI  - Development: heads or tails.

PMID- 23969837
TI  - Phytoestrogens regulate the proliferation and expression of stem cell factors in
      cell lines of malignant testicular germ cell tumors.
AB  - Phytoestrogens have been shown to exert anti-proliferative effects on different
      cancer cells. In addition it could be demonstrated that inhibition of
      proliferation is associated with downregulation of the known stem cell factors
      NANOG, POU5F1 and SOX2 in tumor cells. We demonstrate the potential of Belamcanda
      chinensis extract (BCE) and tectorigenin as anticancer drugs in cell lines of
      malignant testicular germ cell tumor cells (TGCT) by inhibition of proliferation
      and regulating the expression of stem cell factors. The TGCT cell lines TCam-2
      and NTera-2 were treated with BCE or tectorigenin and MTT assay was used to
      measure the proliferation of tumor cells. In addition, the expression of stem
      cell factors was analyzed by quantitative PCR and western blot analysis.
      Furthermore, global expression analysis was performed by microarray technique.
      BCE and tectorigenin inhibited proliferation and downregulated the stem cell
      factors NANOG and POU5F1 in TGCT cells. In addition, gene expression profiling
      revealed induction of genes important for the differentiation and inhibition of
      oncogenes. Utilizing connectivity map in an attempt to elucidate mechanism
      underlying BCE treatments we found highly positive association to histone
      deacetylase inhibitors (HDACi) amongst others. Causing no histone deacetylase
      inhibition, the effects of BCE on proliferation and stem cell factors may be
      based on histone-independent mechanisms such as direct hyperacetylation of
      transcription factors. Based on these findings, phytoestrogens may be useful as
      new agents in the treatment of TGCT.

PMID- 23969839
TI  - Non-coding RNAs: PIWI's new assistant.

PMID- 23969845
TI  - Stable divalent germanium, tin and lead amino(ether)-phenolate monomeric
      complexes: structural features, inclusion heterobimetallic complexes, and ROP
      catalysis.
AB  - Stable germanium(II) and lead(II) amido complexes {LO(i)}M(N(SiMe3)2) (M =
      Ge(II), Pb(II)) bearing amino(ether)phenolate ligands are readily available using
      the proteo-ligands {LO(i)}H of general formula 2-CH2NR2-4,6-tBu2-C6H2OH (i = 1,
      NR2 = N((CH2)2OCH3)2; i = 2, NR2 = NEt2; i = 3, NR2 = aza-15-crown-5) and
      M(N(SiMe3)2)2 precursors. The molecular structures of these germylenes and
      plumbylenes, as well as those of {LO(3)}GeCl, {LO(3)}SnCl and of the congeneric
      {LO(4)}Sn(II)(N(SiMe3)2) where NR2 = aza-12-crown-4, have been determined
      crystallographically. All complexes are monomeric, with 3-coordinate metal
      centres. The phenolate systematically acts as a N^O(phenolate) bidentate ligand,
      with no interactions between the metal and the O(side-arm) atoms in these cases
      (for {LO(1)}(-), {LO(3)}(-) and {LO(4)}(-)) where they could potentially arise.
      For each family, the lone pair of electrons essentially features ns(2) character,
      and there is little, if any, hybridization of the valence orbitals.
      Heterobimetallic complexes {LO(3)}M(N(SiMe3)2).LiOTf, where the Li(+) cation sits
      inside the tethered crown-ether, were prepared by reaction of {LO(3)}M(N(SiMe3)2)
      and LiOTf (M = Ge(II), Sn(II)). The inclusion of Li(+) (featuring a close contact
      with the triflate anion) in the macrocycle bears no influence on the coordination
      sphere of the divalent tetrel element. In association with iPrOH, the amido
      germylenes, stannylenes and plumbylenes catalyse the controlled polymerisation of
      L- and racemic lactide. The activity increases linearly according to Ge(II) ?
      Sn(II) ? Pb(II). The simple germylenes generate very sluggish catalysts, but the
      activity is significantly boosted if the heterobimetallic complex
      {LO(3)}Ge(N(SiMe3)2).LiOTf is used instead. On the other hand, with 10-25 equiv.
      of iPrOH, the plumbylenes afford highly active binary catalysts, converting 1000
      or 5000 equiv. of monomer at 60  degrees C within 3 or 45 min, respectively, in a
      controlled fashion.

PMID- 23969847
TI  - Cryopreservation of mutton snapper ( Lutjanus analis) sperm.
AB  - This study aimed to develop a protocol of semen cryopreservation of the mutton
      snapper Lutjanus analis. The interaction between three extenders ( pH 6.1; 7.8
      and 8.2) , two concentrations of dimethyl sulfoxide ( DMSO, 5 and 10%) and three
      cooling rates ( -90; -60 and -30 degrees C.min-1) on the sperm motility rate and
      motility time were analyzed by a factorial experiment. A sample of 30 fishes (
      1,261 +/- 449 g) collected in the nature was kept in floating net cages. The
      semen was frozen by using cryogenic straws, in nitrogen vapour and transferred,
      later, to liquid nitrogen. Fertilization test was accomplished to evaluate the
      viability of the cryopreserved sperm. The highest sperm motility rate and
      motility time ( P < 0.05) was achieved by combining extender C ( pH 8.2) with
      DMSO ( 10%) and cooling rate of -60 degrees C.min-1 ( P < 0.05) . The use of
      cryopreserved sperm presented fertilization rates higher than 59% validating the
      present protocol for mutton snapper. 

PMID- 23969846
TI  - Nuclear entropy, angular second moment, variance and texture correlation of
      thymus cortical and medullar lymphocytes: grey level co-occurrence matrix
      analysis.
AB  - Grey level co-occurrence matrix analysis (GLCM) is a well-known mathematical
      method for quantification of cell and tissue textural properties, such as
      homogeneity, complexity and level of disorder. Recently, it was demonstrated that
      this method is capable of evaluating fine structural changes in nuclear structure
      that otherwise are undetectable during standard microscopy analysis. In this
      article, we present the results indicating that entropy, angular second moment,
      variance, and texture correlation of lymphocyte nuclear structure determined by
      GLCM method are different in thymus cortex when compared to medulla. A total of
      300 thymus lymphocyte nuclei from 10 one-month-old mice were analyzed: 150 nuclei
      from cortex and 150 nuclei from medullar regions of thymus. Nuclear GLCM analysis
      was carried out using National Institutes of Health ImageJ software. For each
      nucleus, entropy, angular second moment, variance and texture correlation were
      determined. Cortical lymphocytes had significantly higher chromatin angular
      second moment (p < 0.001) and texture correlation (p < 0.05) compared to medullar
      lymphocytes. Nuclear GLCM entropy and variance of cortical lymphocytes were on
      the other hand significantly lower than in medullar lymphocytes (p < 0.001).
      These results suggest that GLCM as a method might have a certain potential in
      detecting discrete changes in nuclear structure associated with lymphocyte
      migration and maturation in thymus. 

PMID- 23969848
TI  - Active polyketides isolated from Penicillium herquei.
AB  - In this work we are reporting the isolation by classical methods of
      chromatography of six polyketides from Penicillium herquei. The compounds
      citreorosein ( 1) , emodin ( 2) , janthinone ( 3) , citrinin ( 4) , citrinin H1 (
      5) and dicitrinol ( 6) were identified by spectral methods of 1D and 2D NMR and
      MS. Compounds 1, 2 and 3 were tested against promastigotes forms of Leishmania
      brasiliensis and 1 and 2 were also assayed against Escherichia coli, Pseudomonas
      aeruginosa and Bacillus subtilis and showed good activity. 

PMID- 23969849
TI  - Evaluation of wound healing and antimicrobial properties of aqueous extract from
      Bowdichia virgilioides stem barks in mice.
AB  - The decoction of the stem barks from Bowdichia virgilioides KUNTH is a folk
      remedy used to treat inflammatory disorders in Latin American and Brazil. In the
      present study, the wound healing activity of aqueous extract of the stem bark
      from B. virgilioides, called AEBv, was evaluated by the rate of healing by wound
      contraction and period of epithelization at different days post-wound using the
      wound excisional model. On day 9, the AEBv-treated animals exhibited
      significative reduction in the wound area when compared with controls. In wound
      infected with S. aureus, the AEBv significantly improved the wound contraction
      when compared to the saline-treated mice. The histological analysis showed that
      AEBv induced a collagen deposition, increase in the fibroblast count and few
      inflammatory cells than compared to saline-treated group. The expression of
      collagen type I was increased in the group treated with AEBv as indicated by
      immunohistochemical staining. In vitro, the AEBv was effective only against S.
      aureus but not against P. aeruginosa. Together, the results of this study
      demonstrate, for the first time, the healing and antimicrobiological effects of
      aqueous extract of the stem bark from B. virgilioides in the therapy of skin
      wounds. 

PMID- 23969850
TI  - Daily and seasonal activity patterns of free range South-American rattlesnake
      (Crotalus durissus).
AB  - This study aimed at describing daily and seasonal variation in the activity of a
      population of South-American rattlesnakes (Crotalus durissus) in a savanna like
      habitat (Cerrado) in Southeastern Brazil. Seasonal and daily activities of snakes
      were evaluated by the number of captures of snakes during road surveys,
      accidental encounters, and relocations by radio-tracking. Our results show that
      climatic variables such as air temperature and rainfall have little influence on
      the activity pattern of rattlesnakes. Our findings indicate that rattlesnakes
      spend most of the day resting and most of the night in ambush posture. The South
      American rattlesnake is active throughout the year with a discrete peak in
      activity of males during the matting season. The possibility of maintaining
      activity levels even during the coldest and driest season can facilitate the
      colonization of several habitats in South America. This possibility currently
      facilitates the colonization of deforested areas by rattlesnakes. 

PMID- 23969851
TI  - Evidence of separate karyotype evolutionary pathway in Euglossa orchid bees by
      cytogenetic analyses.
AB  - Euglossini are solitary bees considered important pollinators of many orchid
      species. Information regarding chromosome organization is available for only a
      small number of species in this group. In the present work, the species Euglossa
      townsendi and E. carolina were analyzed by cytogenetic techniques to collect
      information that may aid the understanding of their evolution and chromosomal
      organization. The chromosome number found was n = 21 for males and 2n = 42 for
      females in the two species. The distribution and amount of heterochromatin
      regions differed in the two species analyzed, where they were classified as
      ?high? or ?low? heterochromatin content, similarly to what has already been
      performed in social bee species of the genus Melipona. Banding patterns found in
      this study suggest that other mechanisms may have occurred in the karyotype
      evolution of this group, unlike those suggested for social bees and ants.
      Karyotype evolution of solitary bees appears to have occurred as an event
      separate from other hymenopterans and did not involve chromosome fissions and
      heterochromatin amplification. 

PMID- 23969844
TI  - Phospho-Ser/Thr-binding domains: navigating the cell cycle and DNA damage
      response.
AB  - Coordinated progression through the cell cycle is a complex challenge for
      eukaryotic cells. Following genotoxic stress, diverse molecular signals must be
      integrated to establish checkpoints specific for each cell cycle stage, allowing
      time for various types of DNA repair. Phospho-Ser/Thr-binding domains have
      emerged as crucial regulators of cell cycle progression and DNA damage
      signalling. Such domains include 14-3-3 proteins, WW domains, Polo-box domains
      (in PLK1), WD40 repeats (including those in the E3 ligase SCF(betaTrCP)), BRCT
      domains (including those in BRCA1) and FHA domains (such as in CHK2 and MDC1).
      Progress has been made in our understanding of the motif (or motifs) that these
      phospho-Ser/Thr-binding domains connect with on their targets and how these
      interactions influence the cell cycle and DNA damage response.

PMID- 23969852
TI  - Chemical, enzymatic and cellular antioxidant activity studies of Agaricus blazei
      Murrill.
AB  - Mushrooms possess nutritional and medicinal properties that have long been used
      for human health preservation and that have been considered by researchers as
      possible sources of free radical scavengers. In this work, the antioxidant
      properties of water extracts from Agaricus blazei Murill, produced by maceration
      and decoction, are demonstrated in vitro. Resistance to oxidation is demonstrated
      through three mechanisms: i) inhibition of enzymatic oxidative process, with 100%
      inhibition of HRP (horseradish peroxidase) and MPO (myeloperoxidase); ii)
      inhibition of cellular oxidative stress, with 80% inhibition of the oxidative
      burst of polymorphonuclear neutrophils (PMNs); and iii) direct action over
      reactive species, with 62% and 87% suppression of HOCl and superoxide anion
      radical (O2* -), respectively. From the data, it was concluded that the aqueous
      extract of A. blazei has significant antioxidant activity, indicating its
      possible application for nutraceutical and medicinal purposes. 

PMID- 23969853
TI  - The role of cyclooxygenase-2 on endurance exercise training in female LDL
      receptor knockout ovariectomized mice.
AB  - Estrogen deprivation in postmenopausal women increases cardiovascular risk.
      Cardiovascular risk as a result of atherosclerosis is able to induce an
      inflammatory disease as far as cyclooxygenase-2 ( COX-2) expression. The purpose
      of the study was to investigate the role of COX-2 on exercise training in female
      mice low-density lipoprotein receptor knockout ( LDL-KO) with or without
      ovariectomy. A total of 15 female C57BL/6 mice and 15 female LDL-KO mice were
      distributed into 6 groups: sedentary control, sedentary control ovariectomized,
      trained control ovariectomized, LDL-KO sedentary, LDL-KO sedentary ovariectomized
      and LDL-KO trained ovariectomized. The ascending part of the aorta was stained
      with H&E and COX-2 expression was assessed by immunohistochemistry. Results
      revealed that ovariectomy as well as exercise training were not able to induce
      histopathological changes in mouse aorta for all groups investigated. LDL-KO mice
      demonstrated plaque containing cholesterol clefts, foamy histiocytes and mild
      inflammatory process for all groups indistinctly. Ovariectomy induced a strong
      immunoexpression in atherosclerosis lesion of LDL-KO mice. Nevertheless, a down
      regulation of COX-2 expression was detected in LDL-KO trained ovariectomized when
      compared to LDL-KO sedentary. Our results are consistent with the notion that
      exercise training is able to modulate COX-2 expression in LDL-KO mice as a result
      of COX-2 down-regulation. 

PMID- 23969854
TI  - Role of the cathelicidin-related antimicrobial peptide in inflammation and
      mortality in a mouse model of bacterial meningitis.
AB  - Antimicrobial peptides (AP) are important components of the innate immune system,
      yet little is known about their expression and function in the brain. Our
      previous work revealed upregulated gene expression of cathelicidin-related AP
      (CRAMP) following bacterial meningitis in primary rat glial cells as well as
      bactericidal activity against frequent meningitis-causing bacteria. However, the
      effect of cathelicidin expression on the progression of inflammation and
      mortality in bacterial meningitis remains unknown. Therefore, we used CRAMP
      deficient mice to investigate the effect of CRAMP on bacterial growth,
      inflammatory responses and mortality in meningitis. Meningitis was induced by
      intracerebral injection of type 3 Streptococcus pneumoniae. The degree of
      inflammation was analyzed in various brain regions by means of
      immunohistochemistry and real-time RT-PCR. CRAMP deficiency led to a higher
      mortality rate that was associated with increased bacterial titers in the
      cerebellum, blood and spleen as well as decreased meningeal neutrophil
      infiltration. CRAMP-deficient mice displayed a higher degree of glial cell
      activation that was accompanied by a more pronounced proinflammatory response.
      Taken together, this work provides insight into the important role of CRAMP as
      part of the innate immune defense against pathogens in bacterial CNS infections.

PMID- 23969856
TI  - Multiple mechanisms repress N-Bak mRNA translation in the healthy and apoptotic
      neurons.
AB  - N-Bak is a neuron-specific BH3-only splice variant of pro-apoptotic Bcl-2 family
      member Bak. We have shown that its mRNA is stable in the neurons, whereas the
      protein cannot be detected by antibodies, suggesting a strong translational
      arrest of the mRNA. Here we identify two regulatory elements in the N-Bak mRNA
      that significantly repress translation in the luciferase reporter assay: an
      upstream open reading frame in the 5'-untranslated region (UTR) and naturally
      spliced exon-exon junction downstream of the premature translation termination
      codon in the 3'UTR. We also show that N-Bak mRNA is stored in granular structures
      in the sympathetic neurons and stays in these granules during intrinsic
      apoptosis. Finally, we confirm the absence of N-Bak protein by quantitative mass
      spectrometry analysis in the healthy, apoptotic or stressed sympathetic and
      cortical neurons. We conclude that N-Bak mRNA is translationally repressed by
      multiple mechanisms, and the protein does not participate in the classical
      apoptosis or cellular stress response.

PMID- 23969858
TI  - Clinical features of takotsubo cardiomyopathy - a single-center experience.
AB  - Takotsubo cardiomyopathy (TTC), also known as transient apical ballooning
      syndrome or stress-induced cardiomyopathy, is a distinctive reversible condition
      often affecting postmenopausal women after a stressful event. It is characterized
      by sudden temporary systolic dysfunction of the apical and/or mid-segments of the
      left ventricle. The underlying mechanisms have not yet been elucidated, but
      several hypotheses include catecholamine cardiotoxicity, microvascular
      dysfunction and coronary artery spasm. We conducted a retrospective descriptive
      study on patients with the discharge diagnosis of TTC from 2003 to 2012 at
      Danbury Hospital, Danbury, Conn., USA. A total of 78 patients met the Modified
      Mayo Criteria for the Diagnosis of TTC and were included in the study. Clinical
      characteristics at baseline, past surgical and medical history including
      psychiatric records were reviewed and recorded. The mean age was 70.5 +/- 14
      years, 87% (n = 68) were women, of which 11.7% (n = 8) were aged <=55 years.
      Depression was present in 20.5% (n = 16) of the patients and anxiety in 30.8% (n
      = 24). Twenty-one patients (27.3%) reported a preceding emotional stressful event
      and 31 (40.3%) had a preceding physical stressor. Fifty patients (64.1%)
      presented with chest pain, 28 (35.9%) had ST-segment elevation upon admission and
      5 (6.3%) died during their hospital stay. TTC is becoming an increasingly
      recognized condition and clinicians should include it in the differential
      diagnosis of patients presenting with a suspected acute coronary syndrome. It is
      frequent in postmenopausal women with preceding physical or emotional stress and
      overall prognosis is good among patients who survive the initial acute phase of
      heart failure. 

PMID- 23969859
TI  - Canine public servants: caring for drug detection dogs.
AB  - Dogs are utilized more and more to seek out illicit and hazardous substances
      under the guidance of humans. Therefore, veterinarians, dog handlers, and
      pharmacists must all collaborate to ensure adequate protection, treatment, and
      care for detection dogs in the line of duty. Ideally, veterinarians and
      pharmacists can work together to train and equip dog handlers with state of the
      art instructions and animal emergency kits that can provide life-saving
      decontamination at the site of exposure. Pharmacists can collaborate with
      veterinarians to provide animal emergency kits containing essential treatment
      aids such as apomorphine, hydrogen peroxide, activated charcoal/sorbitol
      cathartic suspension, ocular irrigants, and instructions and associated devices
      for administration. Immediate intervention provides the best prognosis for canine
      heroes that suffer exposure to occupational toxicological hazards. 

PMID- 23969860
TI  - Transdermal Amlodipine Besylate in Lipoderm for the treatment of Feline
      Hypertension: A Report of Two Cases.
AB  - Primary hypertension may be more common in cats than prior research has
      indicated. Untreated feline hypertension damages organs nourished by a rich
      vascular supply, and kidney disease, ocular impairment and cardiac irregularites
      can be caused by this silent and progressive disorder. The effects of
      hypertension can be minimized with treatment, however, and the long-acting
      dihydropyridine calcium anatgonist amlodipine has been proven safe and effective
      in the management of high blood pressure in cats. Because anxiety can increase
      blood pressure even in normotensive cats, hypertensive feline patients must be
      protected as much as possible from the stress caused by forced medication. A
      compounded preparation of amlodipine in a transdermal gel can be easily applied
      to the feline pinna without subjecting the patient to the trauma of oral
      treatment. In this report, the potency and effectiveness of amlodipine besylate
      in Lipoderm transdermal gel for the treatment of feline hypertension are
      examined, and two case reports describing the outcome of treatment with that
      preparation in hypertensive cats are presented. 

PMID- 23969857
TI  - Withaferin A: a proteasomal inhibitor promotes healing after injury and exerts
      anabolic effect on osteoporotic bone.
AB  - Withania somnifera or Ashwagandha is a medicinal herb of Ayurveda. Though the
      extract and purified molecules, withanolides, from this plant have been shown to
      have different pharmacological activities, their effect on bone formation has not
      been studied. Here, we show that one of the withanolide, withaferin A (WFA) acts
      as a proteasomal inhibitor (PI) and binds to specific catalytic beta subunit of
      the 20S proteasome. It exerts positive effect on osteoblast by increasing
      osteoblast proliferation and differentiation. WFA increased expression of
      osteoblast-specific transcription factor and mineralizing genes, promoted
      osteoblast survival and suppressed inflammatory cytokines. In osteoclast, WFA
      treatment decreased osteoclast number directly by decreasing expression of
      tartarate-resistant acid phosphatase and receptor activator of nuclear factor
      kappa-B (RANK) and indirectly by decreasing osteoprotegrin/RANK ligand ratio. Our
      data show that in vitro treatment of WFA to calvarial osteoblast cells decreased
      expression of E3 ubiquitin ligase, Smad ubiquitin regulatory factor 2 (Smurf2),
      preventing degradation of Runt-related transcription factor 2 (RunX2) and
      relevant Smad proteins, which are phosphorylated by bone morphogenetic protein 2.
      Increased Smurf2 expression due to exogenous treatment of tumor necrosis factor
      alpha (TNFalpha) to primary osteoblast cells was decreased by WFA treatment. This
      was corroborated by using small interfering RNA against Smurf2. Further, WFA also
      blocked nuclear factor kappa-B (NF-kB) signaling as assessed by tumor necrosis
      factor stimulated nuclear translocation of p65-subunit of NF-kB. Overall data
      show that in vitro proteasome inhibition by WFA simultaneously promoted
      osteoblastogenesis by stabilizing RunX2 and suppressed osteoclast
      differentiation, by inhibiting osteoclastogenesis. Oral administration of WFA to
      osteopenic ovariectomized mice increased osteoprogenitor cells in the bone marrow
      and increased expression of osteogenic genes. WFA supplementation improved
      trabecular micro-architecture of the long bones, increased biomechanical strength
      parameters of the vertebra and femur, decreased bone turnover markers
      (osteocalcin and TNFalpha) and expression of skeletal osteoclastogenic genes. It
      also increased new bone formation and expression of osteogenic genes in the femur
      bone as compared with vehicle groups (Sham) and ovariectomy (OVx), Bortezomib
      (known PI), injectible parathyroid hormone and alendronate (FDA approved drugs).
      WFA promoted the process of cortical bone regeneration at drill-holes site in the
      femur mid-diaphysis region and cortical gap was bridged with woven bone within 11
      days of both estrogen sufficient and deficient (ovariectomized, Ovx) mice.
      Together our data suggest that WFA stimulates bone formation by abrogating
      proteasomal machinery and provides knowledge base for its clinical evaluation as
      a bone anabolic agent.

PMID- 23969861
TI  - Veterinary compounding for myasthenia gravis.
AB  - Myasthenia gravis is a neruomuscular disease commonly encountered in veterinary
      medicine. With accurate diagnosis, treatment, and compliant caregivers, the
      prognosis for remission and a normal life is good. Unfortunately, drugs used to
      diagnose and treat myasthenia gravis are frequently unavailable due to
      manufacturer shortages. During these periods, compounding pharmacists can play a
      valuable role in maintaining a good quality of life for these patients by
      providing compounded versions of drugs that are commercially unavailable. 

PMID- 23969862
TI  - Equine anesthesia: triple drip.
AB  - Anesthetization of large animals, such as the horse, is a challenge for
      veterinarians and compounding pharmacists. This article discusses the technique
      of intravenous anesthesia by using a combination of xylazine and ketamine in the
      horse for short-term unconsciousness; a combination of xylazine, diazepam, and
      ketamine, for improved sedation and muscle relaxation; and a combination of
      xylazine, ketamine, and guaifenesin, referred to as Triple Drip, for the maximum
      1-hour duration of unconsciousness. Compounding pharmacists that have the
      facilities and training required to prepare sterile compounds can greatly assist
      equine surgeons in the treatment of veterinarians' most challenging patients. 

PMID- 23969863
TI  - Publication Expansion of United States Pharmacopeial Conventions's Veterinary
      Standards and Clinical Information.
AB  - The United States Pharmacopeial Convention is actively involved in providing
      comprehensive information for compounded veterinary formulations and their
      clinical use. Several United States Pharmacopeia Expert Committees are working to
      develop information establishing the safety and efficacy of necessary
      formulations, drug substance monographs for each active pharmaceutical
      ingredient, and compounding formulation monographs for each dosage form required.

PMID- 23969864
TI  - Golden Ticket to the United States Pharmacopeial Convention's Veterinary
      Internship.
AB  - The future of the United States Pharmacopeial's impact on a broad spectrum of
      entities, including healthcare professionals, government agencies, and academic
      organizations, is expanding. The organization's outreach programs, like the
      summer internship opportunity, are influencing young professionals from a variety
      of specialties and interests. It broadens the view of the student to include
      pharmacy practice, policy issues, the superfluity of opportunities, and
      specialized careers in the healthcare industry. The summer internship program
      instills in its participants an understanding of the United States Pharmacopeia's
      global impact and respect for the organization's dedication to quality. 

PMID- 23969866
TI  - Insurance for the Compounding Business, Part 1: Who is Covered?
AB  - The practice of pharmacy was simpler in the past. Prior to the 1980s, pharmacists
      did not have to worry about "duty to warn" claims, or lawsuits for failure to
      adequately perform a prospective drug review, or claims that the pharmacist
      failed to counsel the patient adequately. In those earlier days, if a pharmacist
      put the right tablet in the bottle with the correct directions, there would be no
      claim or lawsuit. Occasionally, pharmacists would make a medication error.
      Putting the wrong pill in the bottle or mistyping the directions could result in
      serious injury and a significant claim for damages. But the number of errors was
      in keeping with the lower volume of prescriptions filled, and claims were
      relatively few. Today, community pharmacies fill over three billion presciptions
      annually. In keeping with that statistic, the number of claims against
      compounding pharmacists and pharmacies has, understandably, also increased. Not
      all insurance policies for pharmacy professional liability have kept up with the
      changes in pharmacy. With the divergence in pharmacy pracitices, coupled with the
      changes in pharmacists' duties and pharmacy law, the pharmnacist must read and
      understand insurance policies to be sure coverage is adequate. This article is
      intended to help pharmacy owners and pharmacists understand their needs and what
      to look for in their insurance policies. 

PMID- 23969865
TI  - Medication therapy management implementation, part 2: study methodologies,
      barriers, and recommendations to overcome barriers.
AB  - As a required service of the Medicare Modernization Act of 2003, medication
      therapy management services must be offered by all Part D prescription drug-plan
      sponsors in order to improve overall knowledge of medication usage for targeted
      patients. Those targeted patients include patients who have multiple chronic
      diseases, have been prescribed several covered Part D medications, and are paying
      at least $4,000 in medication each year. This article presents the methodolgy
      used by authors to conduct a study of Indiana pharmacists to determine
      pharmacists' attitudes and practices surrounding medication therapy management
      services. This article also discusses some of the barriers and recommendations to
      overcome such barriers encountered by Indiana pharmacists. 

PMID- 23969867
TI  - Excipient choices for special populations.
AB  - Patients with allergies or intolerances and those requiring special diets are
      among the groups that require formulations with special excipients. When
      compounding preparations for this population, the suitability of dyes,
      flavorings, sweeteners, preservatives, gelatins, milk products, gluten, corn,
      soy, nuts, alcohol, chocolate, and other animal-derived ingredients must be
      considered. Unlike manufacturers of foods and nutritional supplements,
      pharmaceutical companies are not required to list certain ingredients of
      manufactured drugs, such as wheat. Therefore, a patient may unknowingly purchase
      a manufactured drug containing an excipient that he cannont tolerate. Once
      informed of a patient's allergy, intolerance, or special diet, the compounding
      pharmacist is able to prepare a prescription from which a particular excipient
      has been eliminated. In many cases, however, the particulars of a patient's
      specific allergy or intolerance are difficult to determine and predict, and thus
      creative thinking is required from the copounding pharmacist. Without question,
      the need for special excipients will continue. 

PMID- 23969868
TI  - Obtaining accreditation by the pharmacy compounding accreditation board, part 4:
      tips for "last minute" preparations.
AB  - One of the most exciting new developments in the world of compounding is the
      opportunity for a pharmacy to obtain accreditation. Other healthcare
      organizations have had that opportunity for years. Compounding pharmaies now have
      an external standard-setting entity to which they can apply for accreditation-the
      Pharmcy Compounding Accreditaion Board-and they are encouraged to do so. The
      pharmacy staff may have extra anxiety the few days before a survey is conducted
      by the Pharmacy Compounding Accreditation Board, but, by following the pre-survey
      tips included in this article, compounding pharmacists and their staff can
      channel the extra energy into productive activites that will help in achieving
      accreditation. 

PMID- 23969869
TI  - Technology for the patient-centric pharmacy.
AB  - All professionals, regardless of the service they provide, must remain current
      with technological developments in their field if they are to serve their clients
      effectively. The healthcare professions are no different, and, in the past,
      practitioners were the main focus of technological advancements in the healthcare
      fields. In today's technologically savvy environment, however, consumer awareness
      has come to the forefront in health care. Some patients are more technologically
      adept than others; technological resources for patients should be simple to
      locate and user-friendly so patients are motivated to engage in self-care
      management. 

PMID- 23969870
TI  - Considerations for implementing United States pharmacopeia chapter 797
      pharmaceutical compounding-sterile preparations, part 9: immediate use compounded
      sterile preparations.
AB  - United States Pharmacopeia Chapter 797 Pharmaceutical Compounding-Sterile
      Preparations pertains to all preadministration manipulations and procedures
      involved in the preparation of sterile compounds of application, implantations,
      infusion, inhalation, injection, insertion, instillation, or irrigation,
      including preparation, storage, and transportation. The chapter does not pertain
      to actual clinical administration of compounded sterile preparations to patient.
      The intent of Chapter 797 is simply to prevent patient harm and fatalities that
      may result from nonsterility, excessive endotoxin load, large content errors in
      strength of correct ingredients, or the presence of incorrect ingredients.
      Because the achievement of sterility requires that facilities meet the minimum
      cleanliness standards, that personnel be trained adequately and undergo periodic
      testing and training in sterilization techniques, and that appropriate principles
      and practices be applied to sustain solution stability, compliance with Chapter
      797, and those that have already met the new standards seem to support them
      strongly. Chapter 797 sets standards for all compounded sterile preparations,
      including those for immediate use. This article discusses the techniques and
      standards used when immediate-use compounded sterile preparations are needed. 

PMID- 23969871
TI  - Testing the long term stability of vancomycin ophthalmic solution.
AB  - Some patients with a keratoprosthesis (artificial cornea) are required to use
      prophylactic vancomycin ophthalmic solution daily for life to prevent infection,
      a regimen which has proven to be highly successful. The objective of this study
      was to determine whether such vancomycin solutions would remain stable at room
      temperature for an extended period of time, beyond that suggested by available
      published stability data and used in current practice. By relaxing the storage
      requirement and extending the expiration date of this solution, it was hoped that
      patient adherence and satisfaction would increase. The studied vancomycin
      ophthalmic solutions were compounded at the Massachusetts Eye and Ear Infirmary,
      Department of Pharmacy Services, Boston, Massachusetts, and were sent to an
      outside laboratory for high-performance liquid chromatography potency testing at
      predefined time points. Vancomycin 14-mg/mL ophthalmic solution compounded with
      0.005% benzalkonium retains potency for at least 60 days at room temperature and
      6 months frozen. Extending the beyond-use dating of vancomycin may lead to
      improved patient adherence by lowering costs and increasing convenience of
      storage and shipment of the medication. 

PMID- 23969872
TI  - Compatibility and Stability of Palonosetron Hydrochloride with Lactated Ringer's
      Hetastarch in Lactated Electrolyte, and Mannitol Injections During Simulated Y
      Site Administration.
AB  - Palonosetron hydrochloride is a longer-acting, selective 5-HT3 receptor
      antagonist that has been approved for the prevention of chemotherapy-induced
      nausea and vomiting ad is being evaluated for the prevention of postoperative
      nausea and vomiting. The objective of this study was to evaluate the physical and
      chemical stability of palonosetron hydrochloride 50mcg/mL when mixed with
      Lactated Ringer's injection, 6% hetastarch in lactated electrolyte injection, or
      15% mannitol injection during simulated Y-site administration. Duplicate samples
      of each admixture were tested. The samples were stored and evaluated for 4 hours
      at room temperature. Physical stability was assessed by turbidimetric and
      particulate measurements, and by visual inspection. Chemical stability was
      assessed by using high-performance liquid chromatography. All of the admixtures
      were clear and colorless when viewed in normal fluorescent room light and when
      viewed with a Tyndall beam. Measured turbidity and particulate content were low
      initially and remained low throughout the observation period. Palonosetron
      hydrochloride concentration was unchanged in any of the samples throughout the
      study period. Palonosetron hydrochlorie is physically and chemically stable with
      Lactated Ringer's injection, 6% hetastarch in lactated elecrolyte injection, or
      15% mannitol injection during simulated Y-site administration over 4 hours at
      ambient room temperature. 

PMID- 23969874
TI  - PostScription: The International Society of Pharmaceutical Compounding: A
      Discussion of its Importance from the Perspective of ISPhC Leadership.

PMID- 23969873
TI  - Chemical stability of admixtures combining ziconotide with fentanyl or sufentanil
      during simulated intrathecal administration.
AB  - Although the U.S. Food and Drug Administration has not approved the combined use
      of intrathecal medications, practitioners frequently prescribe combination
      intrathecal therapy for patients who do not experience adequate analgesia with a
      single intrathecal agent; however, the chemical stability of an analgesic
      combination may influence the frequency of pump refills necessary to maintain
      safe and efective pain control. This investigation was performed to evaluate the
      chemical stability of admixtures containing 25 mcg/mL ziconotide and either 1000
      mcg/mL fentanyl citrate or 1000 mcg/mL sufentanil citrate during simulated
      intrathecal infusion under laboratory conditions at 37 deg C. Admixtures were
      prepared from commercial ziconotide (25 mcg/mL) and lyophilized powders of the
      opioid drugs, sparged with nitrogen to remove dissolved oxygen, and stored in
      implantable intrathecal pumps at 37 deg C. Samples obtained at various intervals
      over the course of 40 days were assessed for drug concentrations by using high
      performance liquid chromatography. The periods of time that the admixtures
      retained > or = 90% and > or = 80% of the initial concentrations of each drug
      (i.e., the 90% and 80% stabilities) were determined by using linear regression
      and 95% confidence intervals. At study end, ziconotide concentrations averaged
      87.5% of the initial concentration in the ziconotide/fentanyl admixture and 89.3%
      of the initial concentration in the ziconotide/sufentanil admixture; opioid
      concentrations were unchanged. Ziconotide was 90% stable for 26 days and 80%
      stable for 58 days (extrapolated) when combined with fentanyl; when combined with
      sufentanil, ziconotide was 90% stable for 33 days and 80% stable for 68 days
      (extrapolated). The opioids were stable throughout the study. At the
      concentrations used in this study, ziconotide/fentanyl and ziconotide/sufentanil
      admixtures were relatively stable. 

PMID- 23969875
TI  - Modulating the M2delta-to-ligand charge transfer transition by the use of
      diarylboron substituents.
AB  - From the reactions between the quadruply bonded complexes M2(T(i)PB)4, where M =
      Mo or W and T(i)PB = 2,4,6-triisopropylbenzoate, and the carboxylic acids HOOC
      C6H4-4-B(mesityl)2, LH (2 equivalents) the complexes trans-M2(T(i)PB)2L2 have
      been prepared. The new compounds have been characterized by (1)H NMR, MALDI-TOF
      MS, UV-Vis-NIR and steady-state emission spectroscopy, time-resolved transient
      absorption spectroscopy and cyclic voltammetry. These results are compared with
      the related properties of the benzoates, M2(T(i)PB)2(O2CPh)2 (prepared similarly)
      and with DFT calculations on model compounds where formate substitutes for
      T(i)PB. The new compounds M2(T(i)PB)2L2 are intensely colored in toluene or THF
      solutions: red (M = Mo) and green (M = W) and the introduction of the p
      B(mesityl)2 group notably shifts these metal to ligand charge transfer
      transitions to lower energy in comparison to the benzoate complexes
      M2(T(i)PB)2(O2C-C6H5)2. Upon the addition of fluoride ions these intense
      absorptions are shifted to much higher energy in a reversible manner for M = Mo. 

PMID- 23969876
TI  - [Biomarkers in allergic conjunctival diseases].

PMID- 23969877
TI  - [Clinical applictions of periostin].

PMID- 23969878
TI  - [Important points for newly revised Japanese pediatric guideline for treatment
      and management of asthma (JPGL) 2012].

PMID- 23969879
TI  - [Adult anaphylaxis in practical medicine].

PMID- 23969880
TI  - [Implementation status of the oral food challenge in Japan].
AB  - BACKGROUND: Oral Food Challenge (OFC) has been covered by medical insurance and
      has been acknowledged as a standardized method for diagnosis of food allergies.
      After 5 years have passed, we would clarify the state of achievement for OFC,
      list up the problems, and produce the basic information for the policies in our
      future. METHOD: The investigation had been done toward allergic specialists for
      Japanese Society of Allergology and the members of Japanese Society of Pediatric
      Allergy and Clinical Immunology. RESULTS: 1353 doctors answered the
      questionnaires. It consists of Practitioners for 49.9%, doctors working for
      hospitals with more than 100 beds for 43.9%, and their specialized fields are
      Pediatrics for 65%, Internal medicine for 18.8%. The examination shows OFC was
      not done for 60% of the total population. Out of 541 facilities, 47.5% for 1 to
      10 OFC per year, 22% for 11 to 30 OFC per year, 11.3% for 31-50 OFC per year,
      8.7% for 51-100 OFC per year, and 10.5% for more than 100 OFC per year. Based on
      the population with the age under 9, the national OFC fill-rate average is 6.4%
      considering ratio of patient population. CONCLUSIONS: OFC has been examined
      widely by allergic specialists in Japan. However, the fill-rate is not enough and
      we need to test more OFC strategically.

PMID- 23969881
TI  - [Analysis of bacterial culture and cytology in nasal smear of Japanese ceder
      pollinosis in pre-season and in season].
AB  - BACKGROUND: Previously, we reported that nasal symptom appeared in some patients
      of Japanese cedar pollinosis (JCP) before season. Over than 50% of them had
      neutrophils (no eosinophil) in their nasal smear (less than 10%; eosinophils),
      and Staphylococcus aureus or epidermis by culture were detected in more than 90%
      of them. We thought the attack caused from rhinitis by Staphylococcus. METHOD:
      For more details of these bacterium in JCP, we enforced bacterial culture in the
      nose and cytology in the nasal smear in asymptomatic (PreAs), symptomatic in pre
      season (PreSy), and symptomatic in season (InSy) of JCP in 2011. RESULTS:
      Positive rates of Staphylococcus aureus were 79%, 75%, 53%, Staphylococcus
      epidermis; 15%, 10%, 16%, Moraxella catarrhalis; 9%, 25%, 19%, and Streptococcus
      Pneumonia; 7%, 12%, 16% in PreAs (n=53), PreSy (60), and InSy (70) respectively.
      Cytology showed that 45% of PreAs (n=53), 65% of PreSy (60) with statistical
      higher in latter group, and 8% of InSy (72) were only neutrophils in nasal smear.
      Six% of PreAs, 2% of PreSy, and 51% of InSy were eosinophils. Forty-three% of
      PreAs with statistical higher than 22% of PreSy and 7% of InSy were nasal cell
      free. CONCLUSION: These results mean the inflammation by Staphylococcus species
      or Moraxella catarrhalis might involve symptom appearance in pre-season.

PMID- 23969882
TI  - [A case of apple allergy with initial symptoms like food-dependent exercise
      induced anaphylaxis].
AB  - A 13-year-old boy with two episodes of anaphylaxis after exercise was suspected
      as food-dependent exercise-induced anaphylaxis (FEIAn). The exercise challenge
      test after ingestion of an apple was performed, because apple was commonly
      contained in meals before the both episodes and a prick test for apple was
      positive. The exercise test was positive accompanied with nasal discharge,
      sneezing, throat discomfort, swelling of the uvula. The patient was instructed to
      refrain from exercise for 4 hours after ingestion of apple. In five months, he
      developed allergic symptoms only by an intake of foods containing heated apple
      without exercise and showed a slight increase in apple-specific IgE from negative
      to 0.51 IU/ml. The prognosis of FEIAn has not been well described. Cases with
      FEIAn to apples like this case require a close follow-up in consideration of
      development of allergic reactions without exercise. 

PMID- 23969884
TI  - Toca 511 gene transfer and 5-fluorocytosine in combination with temozolomide
      demonstrates synergistic therapeutic efficacy in a temozolomide-sensitive
      glioblastoma model.
AB  - Toca 511 (vocimagene amiretrorepvec), an amphotropic retroviral replicating
      vector (RRV), can successfully and safely deliver a functional, optimized
      cytosine deaminase (CD) gene to tumors in orthotopic glioma models. This agent,
      in conjunction with subsequent oral extended-release 5-fluorocytosine (5-FC)
      (Toca FC), is currently under investigation in patients with recurrent high-grade
      glioma . Temozolomide (TMZ) with radiation is the most frequently used first-line
      treatment for patients with glioblastoma, the most common and aggressive form of
      primary brain cancer in adults. However, subsets of patients with certain genetic
      alterations do not respond well to TMZ treatment and the overall median survival
      for patients who respond remains modest, suggesting that combinatorial approaches
      may be necessary to significantly improve outcomes. We show that in vitro TMZ
      delays but does not prevent RRV spread, nor interfere with Toca 511+5-FC-mediated
      cell killing in glioma tumor cells, and in vivo there is no significant
      hematologic effect from the combination of 5-FC and the clinically relevant dose
      of TMZ. A synergistic long-term survival advantage is observed in mice bearing an
      orthotopic TMZ-sensitive glioma after Toca 511 administration followed by
      coadministration of TMZ and 5-FC. These results provide support for the
      investigation of this novel combination treatment strategy in patients with newly
      diagnosed malignant glioma. 

PMID- 23969885
TI  - Comparative antitumor effect among GM-CSF, IL-12 and GM-CSF+IL-12 genetically
      modified tumor cell vaccines.
AB  - Genetically modified cells have been shown to be one of the most effective cancer
      vaccine strategies. An evaluation is made of the efficacy of both preventive and
      therapeutic antitumor vaccines against murine melanoma, using C57BL/6 mice and
      irradiated B16 tumor cells expressing granulocyte and macrophage colony
      stimulating factor (GM-CSF), interleukin-12 (IL-12) or both. Tumor was
      transplanted by the injection of wild-type B16 cells. Tumor growth and survival
      were measured to evaluate the efficacy of vaccination. Specific humoral response
      and immunoglobulin G (IgG) switch were evaluated measuring total IgG and IgG1 and
      IgG2a subtypes against tumor membrane proteins of B16 cells. In preventive
      vaccination, all treated groups showed delayed tumor growth. In addition, the
      group vaccinated to express only GM-CSF achieved 100% animal survival (P<0.005).
      Vaccination with GM-CSF+IL-12-producing B16 cells yielded lesser results (60%
      survival, P<0.005). Furthermore, all surviving animals remained disease-free
      after second tumor implantation 1 year later. The therapeutic vaccination
      strategies resulted in significantly delayed tumor growth, mainly using B16 cells
      producing GM-CSF+IL-12 cytokines, with 70% tumor growth inhibition (P<0.001)
      although none of the animals reached overall survival. The results obtained
      suggest that the GM-CSF+IL-12 combination only increases the efficacy of
      therapeutic vaccines. No differences in classical regulatory T cells were found
      among the different groups. 

PMID- 23969886
TI  - Hydrodynamic immunization leads to poor CD8 T-cell expansion, low frequency of
      memory CTLs and ineffective antiviral protection.
AB  - Hepatotropic pathogens, such as hepatitis B (HBV) and hepatitis C (HCV), often
      escape cellular immune clearance resulting in chronic infection. As HBV and HCV
      infections are the most common causes of hepatocellular carcinoma (HCC),
      prevention of these infections is believed to be key to the prevention of HCC. It
      is believed that an effective immune therapy must induce strong cytotonic T
      lymphocytes (CTLs) that can migrate into the liver, where they can clear infected
      hepatocytes. Here, we compared the induction of CD8 T cells by two different DNA
      immunization methods for T-cell differentiation, function, memory programming and
      their distribution within relevant tissues in a highly controlled fashion. We
      used hydrodynamic tail vein injection of plasmid to establish liver-specific LCMV
      gp antigen (Ag) transient expression, and studied CD8 T cells induced using the
      P14 transgenic mouse model. CD8 T cells from this group exhibited unique and
      limited expansion, memory differentiation, polyfunctionality and cytotoxicity
      compared with T cells generated in intramuscularly immunized mice. This
      difference in liver-generated expansion resulted in lower memory CD8 T-cell
      frequency, leading to reduced protection against lethal viral challenge. These
      data show an unusual induction of naive CD8 T cells contributed to the lower
      frequency of Ag-specific CTLs observed after immunization in the liver,
      suggesting that limited priming in liver compared with peripheral tissues is
      responsible for this outcome. 

PMID- 23969887
TI  - Plasmin(ogen) acquisition by group A Streptococcus protects against C3b-mediated
      neutrophil killing.
AB  - The globally significant human pathogen group A Streptococcus (GAS) sequesters
      the host protease plasmin to the cell surface during invasive disease initiation.
      Recent evidence has shown that localized plasmin activity prevents opsonization
      of several bacterial species by key components of the innate immune system in
      vitro. Here we demonstrate that plasmin at the GAS cell surface resulted in
      degradation of complement factor C3b, and that plasminogen acquisition is
      associated with a decrease in C3b opsonization and neutrophil-mediated killing in
      vitro. Furthermore, the ability to acquire cell surface plasmin(ogen) correlates
      directly with a decrease in C3b opsonization, neutrophil phagocytosis, and
      increased bacterial survival in a humanized plasminogen mouse model of infection.
      These findings demonstrate that localized plasmin(ogen) plays an important role
      in facilitating GAS escape from the host innate immune response and increases
      bacterial virulence in the early stages of infection. 

PMID- 23969888
TI  - Bipedal behaviour in olive baboons: infants versus adults in a captive
      environment.
AB  - The olive baboon is described as a committed quadrupedal primate. However,
      available data show that they actually use a variety of locomotor and postural
      modes. Bipedalism is observed occasionally but spontaneously in captivity and in
      the wild. As observed in other Catarrhini, immature baboons appear to be more
      bipedal than adults: this study aims to provide the necessary quantitative data
      to support this hypothesis, as none has been available so far. The locomotor and
      postural repertoire was quantified for two age classes: infants beginning to
      forage independently, and adults. Our results show that infants appear to have a
      wider repertoire than adults, and bipedal postures and locomotion in infants,
      although infrequent, appear to distinguish them clearly from adults. In
      captivity, behavioural context and morphology are the two main factors that could
      explain age-related positional differences, given a constant ecological context.

PMID- 23969889
TI  - Radiotherapy-induced Gadd45a impairs lacrimal gland epithelial cell migration and
      proliferation.
AB  - Radiotherapy-induced lacrimal gland injury is a serious clinical problem
      currently lacking satisfactory therapeutic strategies. Exploring the mechanisms
      underlying secondary injuries caused by radiation may aid in the development of
      novel targeted medicine. In the current study, growth arrest and DNA damage
      inducible 45 alpha (Gadd45a), a gene which is upregulated in irradiated skin, was
      observed as being overexpressed in the irradiated lacrimal gland. Moreover,
      overexpressed Gadd45a may impair lacrimal gland repair by inhibiting lacrimal
      gland epithelial cell migration and proliferation. Further signalling pathway
      analyses indicated that Gadd45a overexpression suppresses Akt (protein kinase B,
      PKB), P38 and JNK phosphorylation. Thus, the results of the current study
      suggested that Gadd45a may be a therapeutic target in radiation-induced lacrimal
      gland injury.

PMID- 23969890
TI  - A dye-doped optical sensor for the detection of biodiesel in diesel.
AB  - The ability to detect biodiesel at various concentrations in diesel is an
      important goal in several industries. A simple, solvatochromic dye-doped optical
      sensor is presented for quick and direct detection of 0.5 ppm-20% v/v
      FAME/biodiesel in diesel. 

PMID- 23969891
TI  - Tex101 is essential for male fertility by affecting sperm migration into the
      oviduct in mice.

PMID- 23969892
TI  - Prentice revisited.

PMID- 23969894
TI  - Comparing the optical properties of soft contact lenses on and off the eye.
AB  - PURPOSE: The purpose of the current study was to examine the on- and off-eye
      optical performance of two types of soft contact lenses (hydrogel and silicone
      hydrogel). METHODS: The monochromatic aberrations (lambda = 850 nm) of contact
      lenses were measured on-eye using a clinical Shack-Hartmann ocular aberrometer.
      In addition, we used an off-eye single-pass contact lens aberrometer (lambda =
      540 nm) in which the soft contact lens was placed within a wet cell. Comparison
      of the lower and higher order aberrations measured with these two methods
      required compensation for different wavelengths and knowledge of the refractive
      index of the contact lens materials. RESULTS: The measured on-eye sphere and
      spherical aberration values were generally similar to those measured off-eye and
      those specified by the lens manufacturers for both types of soft contact lenses.
      However, there were notable differences, especially for high plus-powered lenses,
      which typically exhibited lower sphere power on the eye than expected from the
      lens specifications and from the off-eye measured powers, both of which were
      almost identical. Longitudinal spherical aberration varied with lens power in the
      hydrogel lenses, as expected from geometric optics theory. Longitudinal spherical
      aberration measurements on- and off-eye, however, deviated significantly from
      that expected of a thin lens with spherical surfaces due to surface
      asphericities. The difference between on- and off-eye optics can be modeled as a
      tear lens or as relative lens thickness changes caused by lens flexure.
      CONCLUSIONS: The results of the current study reveal that the major difference
      between the on-eye lens optics and the manufacturers' specifications is not due
      to lens errors but due to eye-lens interactions, which could be either lens
      flexure or a tear lens forming behind the soft contact lens.

PMID- 23969897
TI  - Changes in the maternal hypothalamic-pituitary-adrenal axis in pregnancy and
      postpartum: influences on maternal and fetal outcomes.
AB  - Overexposure of the developing fetus to glucocorticoids is hypothesised to be one
      of the key mechanisms linking early life development with later life disease. The
      maternal hypothalamic-pituitary-adrenal (HPA) axis undergoes dramatic changes
      during pregnancy and postpartum. Although cortisol levels rise threefold by the
      third trimester, the fetus is partially protected from high cortisol by activity
      of the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (HSD11B2). Maternal HPA
      axis activity and activity of HSD11B2 may be modified by maternal stress and
      disease allowing greater transfer of glucocorticoids from mother to fetus. Here
      we review emerging data from human studies linking dysregulation of the maternal
      HPA axis to outcomes in both the mother and her offspring. For the offspring,
      greater glucocorticoid exposure is associated with lower birth weight and shorter
      gestation at delivery. In addition, evidence supports longer term consequences
      for the offspring including re-setting of the HPA axis and susceptibility to
      neurodevelopmental problems and cardiometabolic disease. For the mother, the
      changes in the HPA axis, particularly in the postpartum period, may increase
      vulnerability to mood disturbances. Further understanding of the changes in the
      HPA axis during pregnancy and the impact of these changes may ultimately allow
      early identification of those most at risk of future disease. 

PMID- 23969898
TI  - Cardiac output is not a significant source of low frequency mean arterial
      pressure variability.
AB  - Spontaneous mean arterial pressure (MAP) variability may be mainly due to
      fluctuations in cardiac output (CO) and total peripheral resistance (TPR). While
      high frequency (HF ~ 0.25 Hz) oscillations in MAP are ultimately driven by
      respiration, the source of low frequency (LF ~ 0.1 Hz) fluctuations has not been
      fully elucidated. It is known that CO buffers these oscillations, but there is no
      evidence on its potential role in also generating them. The main goal was to
      determine whether CO is a source of LF variability in MAP. Six dogs were
      chronically instrumented to obtain beat-to-beat measurements of CO and MAP while
      the dogs were fully awake and at rest. A causal dynamic model was identified to
      relate the fluctuations in CO to MAP. The model was then used to predict the MAP
      fluctuations from the CO fluctuations. The CO fluctuations were able to predict
      about 70% of the MAP oscillations in the HF band but showed no predictive value
      in the LF band. Hence, respiration induces CO fluctuations in the HF band that,
      in turn, cause MAP oscillations, while TPR fluctuations appear to be the dominant
      mediator of LF fluctuations of MAP. CO is not a significant source of these
      oscillations, and it may only be responsible for dampening them, likely through
      the baroreflex. 

PMID- 23969899
TI  - Peptide functionalized gold nanoparticles for colorimetric detection of
      matrilysin (MMP-7) activity.
AB  - A peptide with two cleavage sites for MMP-7 has been synthesized and immobilized
      on gold nanoparticles (AuNPs) through a cysteine residue. Digestion of the
      peptide by MMP-7 decreases its size and net charge, which leads to the
      aggregation of the AuNPs. The color shift caused by aggregation enables a direct
      and quantitative measurement of the concentration and activity of MMP-7 with an
      estimated limit of detection of ~5 nM (0.1 MUg mL(-1)). 

PMID- 23969900
TI  - Non-B, non-C hepatocellular carcinoma (Review).
AB  - Although most hepatocellular carcinoma (HCC) is related to viral infection, there
      is a substantial population of HCC patients (5-20%) who are negative for both
      markers of hepatitis B virus and hepatitis C virus infection [non-B, non-C (NBNC)
      hepatitis] in Japan and the incidence of NBNC-HCC has recently tended to
      increase. The most common cause of liver disease in developed countries is non
      alcoholic fatty liver disease (NAFLD), which includes non-alcoholic
      steatohepatitis (NASH) and its related complications. Increased body mass index
      and diabetes mellitus are associated with developing NAFLD and NASH, which is a
      severe form of NAFLD. Furthermore, increasing clinical evidence supports the fact
      that NAFLD and NASH can progress to liver cirrhosis and even HCC. A detailed
      understanding of the epidemiology, etiology, molecular mechanism, clinical
      features and prognosis of NBNC-HCC could improve our screening and therapy of
      this disease. In this review, we primarily focus on clinical aspects of NBNC-HCC
      and refer to our current knowledge of this cancer.

PMID- 23969901
TI  - mRNA expression pattern of retinoic acid and retinoid X nuclear receptor subtypes
      in human thyroid papillary carcinoma.
AB  - Retinoids have shown potential for the inhibition of tumour growth and
      progression. The objective of this study was to investigate retinoic acid nuclear
      receptor subtypes RAR/RXR and iodothyronine 5'-deiodinase, type I expression
      pattern in papillary thyroid tumour tissue of 26 patients in order to compare
      with those of the non-neoplastic thyroid tissue of the corresponding patients.
      The expression of selected parameters mRNA was examined by semi-quantitative RT
      PCR. Papillary thyroid carcinoma (PTC) expressed RXRgamma, when compared to non
      neoplastic thyroid tissues of the corresponding patients that were lacking
      expression of RXRgamma or its expression was very low. Moreover, we found
      significantly increased expression of RARalpha and RARgamma in the overall group
      of PTC. This increase was detected in cases with positive lymph node metastasis
      (LNM), but not in cases with negative LNM. RARbeta was significantly reduced in
      the subgroup of classic variant (CV). We also detected absence or significantly
      lower expression of hDIO1 mRNA in tumour tissue when compared to non-neoplastic
      tissue in both overall PTC cases and in the CV subgroup. However, the
      significantly decreased levels of hDIO1 mRNA were detected in cases with negative
      LNM but not in cases with positive LNM when compared to corresponding non-tumour
      tissue in both overall PTC cases and in the CV subgroup. Differences in RAR and
      RXR subtype mRNA expression patterns in various PTCs may contribute to the
      immunochemistry data available, and may thus find exploitation in clinical
      oncology, particularly in the differential diagnosis of thyroid neoplasms. 

PMID- 23969902
TI  - Cascade screening in families with inherited cardiac diseases driven by
      cardiologists: feasibility and nationwide outcome in long QT syndrome.
AB  - OBJECTIVES: We assessed the outcome of cascade screening of families with
      congenital long QT syndrome (LQTS) in Danish heart centers. METHODS: Affected
      family members were identified through systematic family screening. RESULTS: In
      total, 228 affected relatives were identified from 90 families. A disease-causing
      mutation useful for presymptomatic genetic testing was found in 82% of probands.
      Two-thirds of affected relatives fulfilled electrocardiographic criteria for the
      diagnosis, whereas diagnosis was based on genetic findings in only one-third. The
      majority of affected relatives were asymptomatic. Symptomatic relatives and
      probands most often presented with syncope, followed by aborted cardiac arrest
      and sudden cardiac death. A serious cardiac event (SCE, such as syncope, aborted
      cardiac arrest or cardiac arrest) was reported by 32% of affected relatives and
      87% of probands (p < 0.0001). Fifty-two percent of affected relatives were on
      beta-blockers and 11% had an implantable cardioverter defibrillator (ICD), as
      compared to 88 and 49% of probands (p < 0.0001). Appropriate ICD therapy was
      given to 13% of affected relatives and to 27% of probands (p = 0.1). CONCLUSIONS:
      Clinically driven cascade screening of Danish LQTS families identified 2-3
      affected relatives per proband. Affected relatives had milder disease courses,
      but SCEs in a subset strongly support screening. Danish cardiologists have
      adopted cascade screening of LQTS families according to specific Danish
      guidelines.

PMID- 23969903
TI  - Radioprotective effect of vitamin E in parotid glands: a morphometric analysis in
      rats.
AB  - The aim of this study was to evaluate the radioprotective effect of vitamin E on
      rat parotid glands by morphometric analysis. Sixty male rats were divided into 5
      groups (n=6): control, in which animals received olive oil solution; olive
      oil/irradiated, in which animals received olive oil and were irradiated with a
      dose of 15 Gy of gamma radiation; irradiated, in which animals were irradiated
      with a dose of 15 Gy gamma radiation; vitamin E, which received alpha-tocopherol
      acetate solution; vitamin E/irradiated, which received alpha-tocopherol acetate
      solution before irradiation with a dose of 15 Gy gamma rays. Half of the animals
      were euthanized at 8 h, and the remaining at 30 days after irradiation. Both
      parotid glands were surgically removed and morphometric analysis of acinar cells
      was performed. Data were subjected to two-way ANOVA and Tukey's test
      (alpha=0.05). Morphometric analysis showed a significant reduction in the number
      of parotid acinar cells at 30 days in olive oil/irradiated and irradiated groups.
      In groups evaluated over time a significant reduction was shown at 30 days in
      olive oil/irradiated and irradiated groups, indicating that ionizing radiation
      caused tissue damage. The vitamin E/irradiated group presented more acinar cells
      than the irradiated group, but no statistically significant difference was
      observed (p>0.05). In conclusion, vitamin E seems to have failed as a
      radioprotective agent on acinar cells in rat parotid glands. 

PMID- 23969904
TI  - Tenascin and fibronectin expression after pulp capping with different hemostatic
      agents: a preliminary study.
AB  - This study investigated the expression of extracellular matrix glycoproteins
      tenascin (TN) and fibronectin (FN) in pulp repair after capping with calcium
      hydroxide (CH), following different hemostasis protocols. Class I cavities with a
      pulp exposure were prepared in 42 human third molars scheduled for extraction.
      Different hemostatic agents (0.9% saline solution, 5.25% sodium hypochlorite and
      2% chlorhexidine digluconate) were used and pulps were capped with CH cement.
      After 7, 30 or 90 days, teeth were extracted, formalin-fixed, and prepared for
      immunohistochemical technique. Hemostatic agents did not influence the expression
      of TN and FN. Both glycoproteins were found in the entire the pulp tissue and
      around collagen fibers, but were absent in the mineralized tissues. In the
      predentin, TN showed positive immunostaining and FN had a variable expression.
      Within 7 days post-treatment, a slightly more pronounced immunostaining on the
      pulp exposure site was observed. Within 30 days, TN and FN demonstrated a
      positive expression around the dentin barrier and at 90 days, a thin and linear
      expression of TN and FN was delimitating the reparative dentin. In conclusion,
      hemostatic agents did not influence TN and FN expression. Immunostaining for TN
      and FN was seen in different regions and periods, demonstrating their role in
      pulp repair. 

PMID- 23969905
TI  - Tumor-infiltrating macrophage and microvessel density in oral squamous cell
      carcinoma.
AB  - Tumor-associated macrophages (TAM) are the main cellular component in stroma of
      many tumors and participate in tumor angiogenesis. The aim of present study was
      to compare the microvascular density (MVD) and infiltrating macrophage density
      (IMD) in oral squamous cell carcinomas (OSCCs) with different histological
      grades. A histomorphometric analysis was performed after immunohistochemistry
      using antibodies such as von-Willebrand factor and CD68. A significant difference
      in MVD was found between well and moderately differentiated OSCCs (p<0.05). TAM
      were largely present in all studied tumors and the IMD was not different among
      OSCCs with different histological grades (p=0.381). Significant correlation
      between MVD and IMD was not observed (p=0.870). In conclusion, these results
      suggest that TAM and angiogenesis have an influence at different histological
      grades of OSCC. However, the lack of correlation between MVD and IMD could
      suggest that angiogenesis does not depend on the number of macrophages present in
      OSCC, but their predominant phenotype. Further studies involving distinct
      phenotypes of macrophages should be done to better understand the influence of
      TAM on the tumor angiogenesis. 

PMID- 23969906
TI  - Frequency of cancer in first-degree relatives of patients with cleft lip and/or
      palate in the Brazilian population.
AB  - Congenital malformations and cancer may share common etiological factors and the
      association between nonsyndromic cleft lip and/or palate (NSCL/P) and cancers has
      been observed in different studies. The objective of this study was to evaluate
      the frequency of cancer in relatives of patients with NSCL/P. This investigation
      was a cross-sectional, case-controlled study, evaluating 358 patients with NSCL/P
      treated at a Referral Center for craniofacial deformities (case group) and 358
      patients without craniofacial alterations (control group). Information concerning
      the gender, age and family history of cancer in first-degree relatives for both
      groups was obtained. The frequency of cancer was 6.4% (n=46) in the studied
      population, with 18 subjects in the case group (5%) and 28 (7.8%) in control. In
      both groups, the most frequently reported cases were those of breast, colorectal,
      stomach, prostate and uterus cancers, but there was no association between the
      two groups. There was no association with a family history of cancer among the
      first-degree relatives (odds ratio=0.62; 95% IC: 0.34 to 1.15), neither when the
      analysis was made by type of cancer. In conclusion, both epidemiological and
      genetic studies have suggested common etiological factors for NSCL/P and cancer.
      However, in this population-based study, no association between cancer and NSCL/P
      could be confirmed. 

PMID- 23969907
TI  - Treatment of intrabony defects with anorganic bone matrix/p-15 or guided tissue
      regeneration in patients with aggressive periodontitis.
AB  - Intrabony periodontal defects present a particular treatment problem, especially
      in patients with generalized aggressive periodontitis (G-AgP). Regenerative
      procedures have been indicated for this clinical situation. The aim of this study
      was to compare treatment outcomes of intrabony periodontal defects with either
      anorganic bone matrix/cell binding peptide (ABM/P-15) or guided tissue
      regeneration (GTR) in patients with G-AgP. Fifteen patients, with two intrabony
      defects >=3 mm deep, were selected. Patients were randomly allocated to be
      treated with ABM/P-15 or GTR. At baseline and at 3 and 6 months after surgery,
      clinical and radiographic parameters and IL-1beta and IL-6 gingival fluid
      concentrations were recorded. There was a significant probing pocket depth
      reduction (p<0.001) for both groups (2.27 +/- 0.96 mm for ABM/P-15 group and 2.57
      +/- 1.06 mm for GTR group). Clinical attachment level gain (1.87 +/- 0.94 mm for
      ABM/P-15 group and 2.09 +/- 0.88 mm for GTR group) was also observed. There were
      no statistically significant differences in clinical parameters between the
      groups. The radiographic bone fill was more expressive in ABM/P-15 group (2.49
      mm) than in GTR group (0.73 mm). In subtraction radiographs, the areas
      representing gain in density were 93.16% of the baseline defect for ABM/P-15
      group versus 62.03% in GRT group. There were no statistically significant
      differences in inter-group and intra-group comparisons with regards to IL-1beta
      and IL-6 quantification. Treatment of intrabony periodontal defects in patients
      with G-AgP with ABM/P-15 and GTR improved significantly the clinical outcomes.
      The use of ABM/P-15 promoted a better radiographic bone fill. 

PMID- 23969908
TI  - Influence of the ultimate torsion on the geometry of dental implants.
AB  - This study evaluated the profile of implants subjected to torsion test. Four
      types of implants (Conexao(r)) were analyzed: Master Porous (MP - external
      hexagon, cylindrical, double-porous surface implants; 11.5 X 3.75 mm), Master
      Screw (MS - external hexagon, cylindrical, machined implants; 11.5 X 3.75 mm),
      Conect Conic (CC - external hexagon, cylindrical, machined implants; 11.5 X 3.5
      mm) and Master Conect AR (CA - internal hexagon, cylindrical, double-porous
      surface implants; 11.5 X 3.75 mm). The Nikon(r) model C profile projector was
      used for the analysis before and after torsion test with a Mackena(r) model MK
      20XX digital torque meter. The measures analyzed in the profile of implants were:
      diameter and height of the platform, diameter of the screw/platform connection,
      angle of the screw/platform connection, external diameter, internal diameter,
      thread pitch, height and length of the thread. Statistical analysis was performed
      using ANOVA and Tukey test at 5% significance level. The torsion test caused a
      visible deformity on the external implant profile. There was a statistical
      difference among the implants before and after torsion (p<0.05) for the
      variables: platform diameter, platform height, diameter of the screw/platform
      connection and length. Changes were observed in platform height of CC and CA,
      fracture of CA implants, fracture of the MP and MS assembler/connectors, and
      internal thread stripping of CC. Thus, it was concluded that excessive or some
      unadvised torque by the manufacturer can lead to changes in different geometric
      measurements of implants. 

PMID- 23969909
TI  - New bone formation around implants inserted on autologous and xenografts
      irradiated or not with IR laser light: a histomorphometric study in rabbits.
AB  - Use of biomaterials and light on bone grafts has been widely reported. This work
      assessed the influence of low-level laser therapy (LLLT) on bone volume (BV) and
      bone implant contact (BIC) interface around implants inserted in blocks of bovine
      or autologous bone grafts (autografts), irradiated or not, in rabbit femurs.
      Twenty-four adult rabbits were divided in 8 groups: AG: autograft; XG: xenograft;
      AG/L: autograft + laser; XG/L: xenograft + laser; AG/I: autograft + titanium (Ti)
      implant; XG/I: xenograft + Ti implant; AG/I/L: autograft + Ti implant + laser;
      and XG/I/L: xenograft + Ti implant + laser. The animals received the Ti implant
      after incorporation of the grafts. The laser parameters in the groups AG/L and
      XG/L were lambda=780 nm, 70 mW, CW, 21.5 J/cm 2 , while in the groups AG/I/L and
      XG/I/L the following parameters were used: lambda=780 nm, 70 mW, 0.5 cm 2 (spot),
      4 J/cm 2 per point (4), 16 J/cm 2 per session, 48 h interval * 12 sessions, CW,
      contact mode. LLLT was repeated every other day during 2 weeks. To avoid systemic
      effect, only one limb of each rabbit was double grafted. All animals were
      sacrificed 9 weeks after implantation. Specimens were routinely stained and
      histomorphometry carried out. Comparison of non-irradiated and irradiated grafts
      (AG/L versus AG and XG/L versus XG) showed that irradiation increased
      significantly BV on both grafts (p=0.05, p=0.001). Comparison between irradiated
      and non-irradiated grafts (AG/I/L versus AG/I and XG/I/L versus XG/I) showed a
      significant (p=0.02) increase of the BIC in autografts. The same was seen when
      xenografts were used, without significant difference. The results of this
      investigation suggest that the use of LLLT is effective for enhancing new bone
      formation with consequent increase of bone-implant interface in both autologous
      grafts and xenografts. 

PMID- 23969910
TI  - Antibiofilm and antibacterial activities of farnesol and xylitol as potential
      endodontic irrigants.
AB  - This study investigated the antibiofilm and antibacterial effects of farnesol and
      xylitol in a series of experiments in order to evaluate their potential use as
      root canal irrigants. The following substances were tested: 0.2% farnesol; 5% and
      20% xylitol; 0.2% farnesol plus 20% xylitol; and saline (control). For comparison
      with an established endodontic irrigant, 2.5% NaOCl was included in each test.
      Three experiments were conducted: the crystal violet assay, to evaluate the
      effects on the biofilm biomass; the dentin disinfection test, to evaluate the
      effects on bacterial viability in biofilms; and the root canal disinfection test,
      to simulate the use in the root canal environment. Farnesol was the most
      effective substance in reducing the biofilm biomass, followed by 20% xylitol. All
      substances affected bacterial viability in biofilms; farnesol showed the best
      results followed by the farnesol/xylitol combination. Irrigation with all
      substances significantly reduced the bacterial load (p<0.001), but only the
      farnesol/xylitol combination was significantly more effective than saline
      (p=0.02). NaOCl was more effective than any other substance tested in the three
      experiments (p<0.001). The findings demonstrated that farnesol affected both the
      biofilm biomass and the viability of cells in the biofilm, while 20% xylitol
      affected only the biofilm biomass. Although not more effective than NaOCl, the
      combination of these two antibiofilm substances has potential to be used in
      endodontics in certain situations. 

PMID- 23969911
TI  - Performance of RaCe instrumentation system in curved root canals: a comprehensive
      analysis by three study methods.
AB  - In this study, curved maxillary molar root canals were instrumented with RaCe
      rotary system to evaluate: 1. the occurrence of canal transportation using a
      radiographic platform; 2. the action of the instruments on the dentin walls,
      centering ability and canal enlargement by analysis of digital images; and the
      percentage of regular dentin surfaces and debris within the canal by histological
      analysis. Ten mesiobuccal roots of extracted human maxillary molars were embedded
      in acrylic resin and sectioned at the middle and apical thirds. Root canal
      shaping was performed using the RaCe rotary system at 250 rpm and 1 Ncm torque.
      Each instrument set was used five times according to a crown-down technique in
      the following sequence: 40/0.10, 35/0.08, 25/0.06, 25/0.04, 25/0.02 (working
      length - WL), 30/0.02 (WL) and 35/0.02 (WL). Each instrument was inserted until
      resistance was felt and then pulled back, followed by brushing movements towards
      all canal walls. Each specimen was assessed by three study methods: radiographic
      platform, digitized image assessment and histological analysis. The radiographic
      platform showed lack of apical transportation. No statistically significant
      difference (Wilcoxon test, p>0.05) was found between the middle and apical thirds
      regarding instrument action on dentin walls, centering ability, area of root
      canal enlargement, percentage of regular dentin surfaces and debris within the
      root canal. It may be concluded that RaCe system is a suitable method for the
      preparation of curved root canals, regarding the maintenance of root canal
      original path, action on dentin walls, canal enlargement and removal of debris
      from the root canal lumen. 

PMID- 23969912
TI  - Effect of sodium trimetaphosphate on hydroxyapatite solubility: an in vitro
      study.
AB  - This study evaluated the effect of different concentrations of sodium
      trimetaphosphate (TMP) with and without fluoride (F) on the concentration of
      calcium (Ca), phosphorus (P) and F in hydroxyapatite (HA). Synthetic HA powder
      (0.15 g) was suspended (n=6) in solutions (75 mL) of TMP at 0%, 0.1%, 0.2%, 0.4%,
      0.6%, 0.8%, 1.0%, 2.0%, 4.0%, 6.0%, 8.0% and 10% concentrations in the presence
      and absence of 100 ppm F and subjected to a pH-cycling process. The precipitates
      were filtrated, dried at 70 degrees  C for 24 h and ground onto a fine powder.
      The concentrations of F (KOH (CaF2) and HCl (FA) soluble), Ca (Arsenazo III), and
      P (molybdate method) in HA were determined. The Ca P, and Ca/P ratio data were
      subjected to Tukey's test and the F data were subjected to Student-Newman-Keuls
      test (p<0.05). The addition of TMP to the samples reduced F deposition to 98%
      (p<0.001). The groups containing 100 ppm F and 0.4% or 0.6% TMP exhibited a
      higher Ca concentration than the group containing only 100 ppm F (p<0.05).
      Furthermore, the HA treated with 0.2% and 0.4% TMP and 100 ppm F showed a higher
      Ca/P ratio than the other groups (p<0.001). In conclusion, TMP at 0.2%, 0.4% and
      0.6% concentrations combined with F seemed to be able to precipitate HA with low
      solubility. However, especially at high concentrations, TMP interferes with F
      deposition on HA. 

PMID- 23969913
TI  - Influence of endodontic sealer composition and time of fiber post cementation on
      sealer adhesiveness to bovine root dentin.
AB  - This study aimed to assess the influence of the type of endodontic sealer
      (salicylate resin-based sealer vs. two endodontic sealers) and the time of fiber
      post cementation after root filling on the post adhesion to bovine root dentin.
      Sixty bovine roots were assigned to six groups (n=10), considering an
      experimental design with two factors (factorial 3x2): endodontic sealer factor in
      three levels [epoxy resin-based sealer (AH Plus), eugenol-based sealer
      (Endofill), and salicylate resin-based sealer plus mineral trioxide aggregate -
      MTA (MTA Fillapex)] and time for post cementation factor in two levels (immediate
      post cementation or 15 days after root canal filling). After post cementation, 2
      mm-thick slices were produced and submitted to push-out test. The failure modes
      were analyzed under a 40* stereomicroscope and scored as: adhesive at
      cement/dentin interface; adhesive at cement/post interface; cement cohesive; post
      cohesive; dentin cohesive; or mixed. Data were analyzed using two-way ANOVA and
      Tukey's post-hoc tests (alpha=0.05). When the fiber posts were cemented
      immediately after the root canal filling, the bond strengths were similar,
      independent of the endodontic sealer type. However, after 15 days, the epoxy
      resin-based sealer presented higher bond strength than the other sealers
      (p<0.05). Comparison between each sealer in different experimental times did not
      reveal any differences. The main failure type was adhesive at dentin/cement
      interface (89.4%). The time elapsed between the root canal filling and post
      cementation has no influence on post/root dentin adhesion. On the contrary, the
      type of endodontic sealer can influence the adhesion between fiber posts and root
      dentin. 

PMID- 23969914
TI  - Effect of sealant application and thermal cycling on bond strength of tissue
      conditioners to acrylic resin.
AB  - The aim of this study was to evaluate the effect of sealer application and
      thermal cycling on the bond strength between tissue conditioners and acrylic
      resin, and to observe the type of bond failure. Two hundred eighty-eight
      specimens (10x16x3 mm) were made of an acrylic resin (Lucitone 500, Dentsply)
      using a metal muffle. Specimens were divided into four groups according to the
      tissue conditioner (Coe-Comfort, GC or Dentusoft, Densell) used and whether or
      not a sealer (Eversoft Soft Liner Sealer, Myerson) was applied. Each of the four
      groups was subdivided into other six subgroups (n=12) to undergo thermocycling
      for 45, 90, 135, 180 or 210 cycles with a dwell time of 60 s, or to be left non
      thermocycled (control). Tensile bond strength was measured in a universal testing
      machine at a crosshead speed of 5 mm/min. Sealant application had no effect on
      the tensile bond strength of the relined acrylic resin, regardless of the tissue
      conditioner used (Coe-Comfort: p=0.306 and Dentusoft: p=0.1501). The number of
      thermal cycles had a significant effect on the tensile bond strength of the
      relined acrylic resin (Coe-Comfort: p=0.002 and Dentusoft: p<0.001). Both tissue
      conditioners presented similar bond strength to acrylic resin. For both tissue
      conditioners, sealer coatings had no influence on bond strength, while different
      numbers of thermal cycles affected that mechanical property. 

PMID- 23969915
TI  - In vitro enamel remineralization by low-fluoride toothpaste with calcium citrate
      and sodium trimetaphosphate.
AB  - The objective of this study was to evaluate in vitro the effect of a low fluoride
      toothpaste (450 ugF/g, NaF) combined with calcium citrate (Cacit) and sodium
      trimetaphosphate (TMP) on enamel remineralization. Bovine enamel blocks had the
      enamel surface polished sequentially to determine the surface hardness. After
      production of artificial carious lesions, the blocks selected by their surface
      hardness were submitted to remineralization pH cycling and daily treatment with
      dentifrice suspensions (diluted in deionized water or artificial saliva):
      placebo, 275, 450, 550 and 1,100 ugF/g and commercial dentifrice (positive
      control, 1,100 ugF/g). Finally, the surface and cross-section hardness was
      determined for calculating the change of surface hardness (%SH) and mineral
      content (%?Z). Fluoride in enamel was also determined. The data from %SH, %?Z and
      fluoride were subjected to two-way analysis of variance followed by Student
      Newman-Keuls's test (p<0.05). The mineral gain (%SH and %?Z) was higher for
      toothpastes diluted in saliva (p<0.05), except for the 450 ugF/g dentifrice with
      Cacit/TMP (p>0.05). The 450 Cacit/TMP toothpaste and the positive control showed
      similar results (p>0.05) when diluted in water. A dose-response was observed
      between fluoride concentration in toothpastes and fluoride present in enamel,
      regardless of dilution. It was concluded that it is possible to enhance the
      remineralization capacity of low F concentration toothpaste by of organic (Cacit)
      and inorganic (TMP) compounds with affinity to hydroxyapatite. 

PMID- 23969916
TI  - Comparison of silorane and methacrylate-based composites on the polymerization
      heat generated with different light-curing units and dentin thicknesses.
AB  - This study evaluated the temperature variation in the pulp chamber during
      photoactivation of two restorative composite resins (Filtek P90 silorane-based
      composite and Heliomolar methacrylate-based composite) with either a quartz
      tungsten-halogen (QTH) or light-emitting diodes (LED) light-curing unit (LCU) and
      using dentin thicknesses (0.5 and 1.0 mm). Standardized cavities (2x2x2 mm) were
      prepared in 80 bovine incisors, which were randomly assigned to 8 groups
      according to the photoactivation method and dentin thickness. Filtek P90 and
      Heliomolar (both in shade A3) were used with their respective adhesive systems
      (P90 self-etch primer / P90 adhesive bond and Excite adhesive). All experiments
      were carried out in a controlled environment (37 degrees C). The temperature
      variations ( degrees C) were recorded using a digital thermometer attached to a K
      type thermocouple. The results were analyzed statistically by ANOVA and Tukey's
      test (alpha=0.05). For composite/dentin thickness interaction, temperature
      increase was significantly higher in 0.5 mm dentin thickness (40.07 degrees C)
      compared with 1.0 mm dentin thickness (39.61 degrees C) for Filtek P90. For
      composite/LCU interaction, the temperature increase was significantly higher for
      Filtek P90 (39.21 degrees C - QTH and 40.47 degrees C - LED) compared with
      Heliomolar (38.40 degrees C - QTH and 39.30 degrees C - LED). The silorane-based
      composite promoted higher temperature increase in the pulp chamber than the
      methacrylate-based composite. 

PMID- 23969917
TI  - Effect of carbamide peroxide bleaching gel on composite resin flexural strength
      and microhardness.
AB  - This study investigated the effect of 16% carbamide peroxide (Whiteness
      Perfect/FGM) on the Vickers microhardness and flexural strength of the
      restorative composites Filtek Z100 (hybrid), Filtek Z350 (nanofill), Brilliant
      (micro-hybrid) and Opallis (micro-hybrid). Disc-shaped (4x2 mm; n=5) and bar
      shaped (12x2x1 mm; n=10) specimens of each restorative material were randomly
      divided into 2 groups: (G1) 16 weeks stored in distilled water; (G2) 16 weeks
      stored in distilled water, with 16% carbamide peroxide application during 6 h per
      day for the last 4 weeks. The mechanical properties were evaluated using a
      Vickers microhardness tester and a mechanical testing machine. Data were analyzed
      by two-way ANOVA and Tukey's (HSD) post-hoc test (alpha=0.05). Filtek Z100
      presented the highest microhardness value, followed by Filtek Z350 and finally by
      Brilliant and Opallis (p=0.00). Filtek Z100 and Brilliant exhibited the highest
      flexural strength value, followed by Filtek Z350 and Opallis (p=0.00). Bleaching
      treatment decreased significantly microhardness of Brilliant and Opallis
      (p=0.00). The flexural strength of all studied materials was not affected by the
      home bleaching (p=0.28). 

PMID- 23969918
TI  - One-year evaluation of a simplified ethanol-wet bonding technique: a randomized
      clinical trial.
AB  - The objective of this randomized clinical trial was to evaluate the clinical
      performance of adhesive restorations using a three-step etch-and-rinse adhesive
      (TSER), a one-step self-etching adhesive (OSSE), and a simplified ethanol-wet
      bonding technique (EWBT) prior to the application of a composite resin in non
      carious cervical lesions. Ninety-three restorations (31 for each group) were
      placed in 17 patients by a single operator. No cavity preparation was performed.
      After 6 and 12 months, the restorations were assessed by two previously trained
      examiners using modified Ryge criteria for retention (kappa=1.00) and marginal
      adaptation/staining (kappa=0.81), and the results were analyzed by Fisher's exact
      and Kruskal-Wallis tests, respectively. No significant differences were observed
      among groups at the 6- and 12-month time points for any of the assessed criteria
      (p>=0.05). The intra-group analysis performed by Cochran's test (for retention)
      and Wilcoxon test (for marginal adaptation/staining) revealed significant
      differences between the baseline/12-month time intervals in marginal adaptation
      in OSSE (p=0.0180) and in marginal staining in TSER (p=0.0117). The survival
      analysis for retention criteria performed using a log-rank test did not show
      significant differences (p>0.05). The restorations placed using the simplified
      EWBT performed equally well as the other adhesive strategies employed. 

PMID- 23969919
TI  - Impact of experimental nano-HAP pastes on bovine enamel and dentin submitted to a
      pH cycling model.
AB  - This in vitro study evaluated the preventive potential of experimental pastes
      containing 10% and 20% hydroxyapatite nanoparticles (Nano-HAP), with or without
      fluoride, on dental demineralization. Bovine enamel (n=15) and root dentin (n=15)
      specimens were divided into 9 groups according to their surface hardness: control
      (without treatment), 20 Nanop paste (20% HAP), 20 Nanop paste plus (20% HAP +
      0.2% NaF), 10 Nanop paste (10% HAP), 10 Nanop paste plus (10% HAP + 0.2% NaF),
      placebo paste (without fluoride and HAP), fluoride paste (0.2% NaF), MI paste
      (CPP-ACP, casein phosphopeptide-amorphous calcium phosphate), and MI paste plus
      (CPP-ACP + 0.2% NaF). Both MI pastes were included as commercial control products
      containing calcium phosphate. The specimens were treated with the pastes twice a
      day (1 min), before and after demineralization. The specimens were subjected to a
      pH-cycling model (demineralization-6-8 h/ remineralization-16-18 h a day) for 7
      days. The dental subsurface demineralization was analyzed using cross-sectional
      hardness (kgf/mm 2 , depth 10-220 um). Data were tested using repeated-measures
      two-way ANOVA and Bonferroni's test (p<0.05). The only treatment able to reduce
      the loss of enamel and dentin subsurface hardness was fluoride paste (0.2% NaF),
      which differed significantly from the control at 30- and 50-um depth (p<0.0001).
      The other treatments were not different from each other or compared with the
      control. The experimental Nanop pastes, regardless of the addition of fluoride,
      were unable to reduce dental demineralization in vitro. 

PMID- 23969920
TI  - Properties of composite materials used for bracket bonding.
AB  - The purpose of this study was to evaluate in vitro the shear bond strength to
      enamel, flexural strength, flexural modulus, and contraction stress of one
      orthodontic composite and two flowable composites. Orthodontic brackets were
      bonded to 45 human maxillary premolars with the composites Transbond XT, Filtek Z
      350 flow and Opallis flow and tested for shear bond strength. For measurement of
      flexural strength and flexural modulus, specimens were fabricated and tested
      under flexion. For the contraction stress test, cylindrical specimens were tested
      and an extensometer determined the height of the specimens. The data were
      subjected to one-way ANOVA and Tukey's test (alpha=0.05). The shear bond strength
      values were significantly lower (p<0.05) for the flowable composites compared
      with the orthodontic composite. For the flexural strength, no statistically
      significant difference was found among the composites (p>0.05) while the flexural
      modulus was significantly higher (p<0.05) for Transbond XT than for Filtek Z-350
      flow and Opallis flow. The orthodontic composite presented significantly lower
      contraction stress values than the flowable composites (p<0.05). The light
      activated orthodontic composite material presented higher flexural modulus and
      shear bond strength and lower contraction stress than both flowable composites. 

PMID- 23969921
TI  - Extranodal nasal NK/T-cell lymphoma: a rare oral presentation and FASN, CD44 and
      GLUT-1 expression.
AB  - Extranodal natural killer (NK)/T-cell lymphoma is an aggressive malignant tumor
      with distinctive clinicopathological features, characterized by vascular invasion
      and destruction, prominent necrosis, cytotoxic lymphocyte phenotype and a strong
      association with Epstein-Barr virus. Here is reported an extranodal nasal NK/T
      cell lymphoma case, involving the maxillary sinus, floor of the orbit, and
      interestingly extending to the oral cavity through the alveolar bone and buccal
      mucosa, preserving the palate, leading to a primary misdiagnosis of aggressive
      periodontal disease. Moreover, this work investigated for the first time the
      immunohistochemical expression of fatty acid synthase (FASN) and glucose
      transporter 1 (GLUT-1) proteins in this neoplasia. FASN showed strong
      cytoplasmatic expression in the neoplastic cells, whereas GLUT-1 and CD44 were
      negative. These findings suggest that the expression of FASN and the loss of CD44
      might be involved in the pathogenesis of the extranodal nasal NK/T-cell lymphoma,
      and that GLUT-1 may not participate in the survival adaptation of the tumor cells
      to the hypoxic environment. Further studies with larger series are required to
      confirm these initial results. 

PMID- 23969922
TI  - Autotransplantation of a mandibular third molar: a case report with 5 years of
      follow-up.
AB  - This paper describes the autologous transplantation of a mandibular right third
      molar to replace the residual roots of the second molar in the same quadrant,
      preserving function and aesthetics. A 5-year clinical and radiographic follow-up
      was undertaken. After transplantation, the donor tooth received endodontic
      treatment and placement of calcium hydroxide, which was periodically replaced
      every 3 months until the filling of the root canals, totalizing a period of 1
      year, when apical closure was confirmed. The tooth was in perfect functional and
      aesthetic conditions 5 years after beginning of treatment. Autotransplantation is
      a feasible option for replacing missing teeth when a donor tooth is available.
      The autotransplantation of a right mandibular third molar with compromised
      function and aesthetics to replace the residual roots resulting from coronal
      destruction due to extensive carious lesion of the second molar in the same
      quadrant was a viable treatment alternative. 

PMID- 23969923
TI  - Arthritis epidemiology impacts pharmacists.
AB  - Epidemiologic data indicates that the occurrence of arthritis and related
      diseases will have a significant impact upon the practice of pharmacy. The two
      most prevalent diseases are osteoarthritis and rheumatoid arthritis. These two
      diseases currently affect millions of Americans. Data is presented that
      facilitate awareness of the need to develop ways to economically provide
      pharmaceutical care with the expanding epidmeic of rheumatic diseases. 

PMID- 23969924
TI  - Compounding challenges for immunocompromised patients.
AB  - Compounding pharmacists play a vital role in the prevention, duration, and
      conclusion of diseases and infections for immunocompromised patients. Caused by
      deficiencies such as the human immunodeficiency virus, acquired immunodeficiency
      virus and cancers, which warrant immunosuppression during chemotherapy,
      immunodeficiency renders the patient vulnerable to viruses, infections, and
      diseases that, in the immunocompromised state, could develop lethally. By working
      closely with patients, compounding pharmacists are able to provide correct
      dosages, strengths, and drug combinations for each individual situation. 

PMID- 23969925
TI  - Differentiation and treatment of hypothyroidism, functional hypothyroidism, and
      functional metabolism.
AB  - Less than optimal thyroid effects can occur for many reasons, including lack of
      production, excessive binding, reduced conversion to the active form of thyroid,
      poor intracellular transport, poor receptor response, or autoimmune and toxicity
      issues. Differentiation of where the problem or problems causing the symptoms of
      hypothyroidism to occur is a key to the return to optimal thyroid response and
      successful treatment outcome. The concept of hypothyroidism, functional
      hypothyroidism, and functional hypometabolism as an alternative method to
      describe classical subclinical hypothyroidism symptoms according to the source of
      the malfunction are discussed in this article. The author also presents a unique
      method of using standard thyroid measurements to determine the areas of
      dysfunction and discusses the possible reasons for low production, excessive
      binding, poor conversion, and suboptimal receptor response. Appropriate treatment
      options for each area are discussed, including nutritional requirements. Thyroid
      replacement therapy options are presented and individualization of therapy based
      on need established with use of the thyroid gradient levels is discussed.
      Individualization of thyroid therapy will often require the use of compounded T3
      or T4/T3 combination therapy. Compounding thyroid replacement allows for avoiding
      fillers that can interfere with absorption, unwanted diluents, unknown or
      standardized ingredients from animal sources providing more sustained action with
      less side effects, and individualizing the ratio of T4 and T3 initially, and as
      improvements are made in the patient's ability to convert T4 to T3. 

PMID- 23969926
TI  - Case reports: compounding to relieve arthritis pain.
AB  - Arthritis is an ancient disorder that defies cure. The management of arthritis
      may require medication, surgery, and/or nonpharmacologic treatment, and patients
      whose pain responds to drug therapy often achieve substantial benefit from a
      compounded preparation. Customized to include analgesics in combinations and
      concentrations not found in commercially manufactured medications, a pain
      relieving compound can be prepared in a transdermal form that minimizes the risk
      of adverse effects associated with some oral medications. In this article, we
      present case reports of patients whose arthritic pain was relieved by a
      pharmaceutical compound. Formulations effective in treating inflammatory pain are
      also provided. 

PMID- 23969927
TI  - Symbols: historic and current uses.
AB  - From hieroglyphs to barcodes, symbols have been used throughout history. Symbols
      can be observed on traffic signs, warning signs that are affixed to building
      fronts, doors of public restrooms to show gender-specific usage, and caution
      signs on caustic or poisonous chemicals; even Braille, a system of writing and
      printing for the blind, is a symbol form. This article includes a brief
      discussion on the psychology of symbols, history of symbols, symbols used by
      alchemists and pharmacists, and the current use of symbols. 

PMID- 23969928
TI  - Medication therapy management implementation, part 3: barriers and
      recommendations to overcome barriers.
AB  - As a required service of the Medicare Modernization Act of 2003, medication
      therapy management services must be offered by all Part D prescription drug-plan
      sponsors in order to improve overall knowledge of medication usage for targeted
      patients. Those targeted patients include patients who have multiple chronic
      diseases, have been prescribed several covered Part D medications, and are paying
      at least $4,000 for their medication each year. This article discusses some of
      the barriers and recommendations to overcome such barriers encountered by Indiana
      pharmacists. 

PMID- 23969929
TI  - Insurance for the compounding pharmacy business, part 2: what, when, and where.
AB  - The practice of pharmacy was simpler in past years. Prior to the 1980s,
      pharmacists did not have to worry about "duty to warn" claims, lawsuits for
      failure to adequately perform a prospective drug review, or claims that the
      pharmacist failed to counsel the patient adequately. In those earlier days, if a
      pharmacist put the right tablet in the bottle with the correct directions, there
      would be no claim or lawsuit. Occasionally, pharmacists would make a medication
      error. Putting the wrong pill in the bottle or mistyping the directions could
      result in serious injury and a significant claim for damages, but the number of
      errors was in keeping with the lower volume of prescirptions filled, and claims
      were relatively few. Today, community pharmacies fill over three billion
      prescriptions annually. In keeping with that statistic, the number of claims
      against compounding pharmacists and pharmacies has, understandably, also
      increased. Not all insurance policies for pharmacy professional liability have
      kept up with the changes in pharmacy. With the divergence in pharmacy practices,
      coupled with the changes in pharmacists' duties and today's pharmacy law, the
      pharmacist must read and understand insurance policies to be sure they have
      adequate coverage for their professions. The information contained within this
      article is provided to help the pharmacy owners and pharmacists understand their
      needs and what to look for in their policies. 

PMID- 23969930
TI  - Quality-control analytical methods: overview of beyond-use dating for compounded
      sterile preparations.
AB  - United States Pharmacopeia Chapter 797 provides guidelines and standards that
      deal with the preparation, compounding, and labeling of compounded sterile
      preparations. These standards ensure patient care and safety by defining safe
      practice. The Chapter gives instructions on determining beyond-use dates for the
      different risk categories associated with compounded preparations. Each of these
      categories has specific aspects of environmental personnel, and situational
      deterrents that Chapter 797 requires to be taken into account. By following the
      standards of Chapter 797, compounding pharmacists can alleviate danger to the
      patient and themselves in any situation. 

PMID- 23969931
TI  - Basics of compounding: United States pharmacapeia general chapter 797
      pharmaceutical compounding-sterile preparations, part 10: first revision: the
      main changes, events, and rationale.
AB  - From 2005 to 2007, the United States Pharmacopeia's Sterile Compounding Committee
      revolutionized sterile preparation practices with a thorough revision to a
      monumental standard. By revising United States Pharmacopeia General Chapter 797,
      they defined safe procedures for compounded sterile preparations in profound
      detail. From proper hygiene to air quality control, the revised Chapter 797 aims
      to reduce complications related to treatment with compounded sterile
      preparations, offers invaluable information to those involved in the compounding
      process, and establishes standards to improve the quality of the compounding
      process. The vast intellect, innovative review process, and dedicated research
      incorporated into this revision have assisted those involved with compounding
      pharmacy around the world. 

PMID- 23969932
TI  - Physical Compatibility and Chemical Stability of a Concentrated Solution of
      Atropine Sulfate (2 mg/mL) for Use as an Antidote in Nerve Agent Casualties.
AB  - Atropine is one of the preferred antidotes for nerve gas exposure. Effective
      therapy requires large doses. Stockpiling of atropine in forms currently
      available commercially can be costly and can require a large storage area. Other
      problems in using the commercial product are the time required to break the large
      number of ampules needed for treatement, and the large volume of medication that
      must be administered. A preparation of concentrated atropine for injection from
      atropine powder is the ideal solution, but the stability of this preparation is
      unknown. A formulation for concentrated atropine sulfate solution (2 mg/mL) was
      developed using pharmaceutical-grade powder. The solution was prepared in
      isotonic saline solution and packaged in polypropylene syringes, which were
      sealed with syringe caps. Assessment of physical stability under several storage
      conditions was based on clarity, color, and pH monitoring. Chemical stability of
      the preparation was determined by using a stability-indicating high-performance
      liquid chromatographic method. All solutions remained clear and colorless, and
      the pH changed only slightly over the study period. The potency of the atropine
      sulfate solution remained above the United States Pharmacopeia limit of 93% for
      the duration of the study. The solutions were physically compatible and
      chemically stable when stored for 28 days at 35 deg C and exposed to light, 364
      days at 23 deg C and exposed to light, or 364 days at 5 deg C and protected from
      light. Concentrated solutions of atropine sulfate can be compounded quickly and
      easily by using commercially available pharmaceutical-grade powder as the active
      ingredient. The extended shelf-life allows the preparation to be readily
      available in the field as required. 

PMID- 23969933
TI  - Chemical Stability of Admixtures Containing Ziconotide 25 mcg/mL and Morphine
      Sulfate 10 mg/mL or 20 mg/mL During Simulated Intrathecal Administration.
AB  - The chemical stability of an intrathecally administered analgesic combination may
      influence the frequency of pump refills necessary to maintain safe and effective
      analgesia. Previous work has shown that the stability of ziconotide at body
      temperature is reduced substantially by the presence of morphine sulfate 35
      mg/mL. The current study was performed to evaluate the chemical stability of
      admixtures combining ziconotide with lower concentrations of morphine sulfate
      during simulated intrathecal infusion under laboratory conditions at 37 deg C.
      Admixtures containing ziconotide 25 mcg/mL and morphine sulfate 10 mg/mL or 20
      mg/mL were stored in implantable intrathecal pumps at 37 deg C and in control
      vials at 37 deg C or 5 deg C. Samples were obtained over 60 days (admixture
      containing morphine sulfate 10 mg/mL) or 28 days (admixture containing morphine
      sulfate 20 mg/mL) and drug concentrations were assessed by high-performance
      liquid chromatography. Estimates of the time intervals that each admixture
      retained > or= 90% and > or = 80% of the initial concentrations of both drugs
      (i.e., the 90% and 80% stabilites) were based on 95% confidence bounds obtained
      via linear regression. Morphine sulfate 10 mg/mL, the mean ziconotide
      concentration declined to 81.4% of the initial concentration in 60 days, and 90%
      and 80% stabilites were maintained for 34 days and 65 days, respctively. In the
      admixture containing morphine sulfate 20 mg/mL, the mean ziconotide concentration
      declined to 85.3% of the initial concentration in 28 days, and 90% and 80%
      stabilities were maintained for 19 days and 37 days, respectively. Decreasing the
      concentration of morphine in an admixture containing ziconotide improves the
      stablity of ziconotide. 

PMID- 23969934
TI  - Stability of Metronidazole Benzoate in SyrSpend SF One-Step Suspension System.
AB  - The objective of this study was to determine the stability of metronidazole
      benzoate suspension in SyrSpend SF One-Step Suspension system. The studied
      samples were packaged in 60-mL amber plastic prescription bottles, which were
      stored protected from light under controlled environmental conditions for a
      period of 360 days. Stability of metronidazole benzoate suspension in SyrSpend SF
      was assessed based on retention of initial color or appearance, pH of suspension,
      and recovery of metronidazole benzoate from the packaged product. Duplicate
      samples were evaluated at each predefined time interval. An assay method by high
      performance liquid chromatography was validated for its specificity and stability
      indicating characteristscs through a forced-degradation study, and was used in
      metronidazole benzoate assay. Metronidazole benzoate in SyrSpend SF retained its
      normal appearance of an opaque suspension, with acceptable pH values ranging from
      4.43 to 4.53 (range 4.45 +/- 0.5). Recovery of metronidazole benzoate at
      subsequent time points was within 90% to 110% of inital concentration for samples
      stored at refrigerated temperature (2 deg C to 8 deg C), and ambient condition
      (25 deg C/60% relative humidity), with no detectable changes in chromatographic
      profile for most tested samples. The rates of change in potency for metronidazole
      benzoate were determined under the assumptions of first-order kinetics, and the
      time to reach 90% to 110% initial concentration was determined to be 366 days for
      samples in ambient storage, or 716 days for samples stored at refrigerated
      temperature. Metronidazole benzoate in SyrSpend SF, which was packaged in amber
      plastic prescription bottles, is stable for at least 1 year when stored protected
      from light at ambient condition (25 deg C/60% relative humidity). The shelf life
      for this product may be extended to 2 years when stored at refrigerated
      temperature. 

PMID- 23969935
TI  - PostScription: Supporting Compounding Around the World.

PMID- 23969936
TI  - Characterization and clinical relevance of ALDHbright populations in prostate
      cancer.
AB  - PURPOSE: High aldehyde dehydrogenase (ALDH) has been suggested to selectively
      mark cells with high tumorigenic potential in established prostate cancer cell
      lines. However, the existence of cells with high ALDH activity (ALDH(bright)) in
      primary prostate cancer specimens has not been shown so far. We investigated the
      presence, phenotype, and clinical significance of ALDH(bright) populations in
      clinical prostate cancer specimens. EXPERIMENTAL DESIGN: We used ALDEFLUOR
      technology and fluorescence-activated cell-sorting (FACS) staining to identify
      and characterize ALDH(bright) populations in cells freshly isolated from clinical
      prostate cancer specimens. Expression of genes encoding ALDH-specific isoforms
      was evaluated by quantitative real-time PCR in normal prostate, benign prostatic
      hyperplasia (BPH), and prostate cancer tissues. ALDH1A1-specific expression and
      prognostic significance were assessed by staining two tissue microarrays that
      included more than 500 samples of BPH, prostatic intraepithelial neoplasia (PIN),
      and multistage prostate cancer. RESULTS: ALDH(bright) cells were detectable in
      freshly excised prostate cancer specimens (n = 39) and were mainly included
      within the EpCAM((+)) and Trop2((+)) cell populations. Although several ALDH
      isoforms were expressed to high extents in prostate cancer, only ALDH1A1 gene
      expression significantly correlated with ALDH activity (P < 0.01) and was
      increased in cancers with high Gleason scores (P = 0.03). Most importantly,
      ALDH1A1 protein was expressed significantly more frequently and at higher levels
      in advanced-stage than in low-stage prostate cancer and BPH. Notably, ALDH1A1
      positivity was associated with poor survival (P = 0.02) in hormone-naive
      patients. CONCLUSIONS: Our data indicate that ALDH contributes to the
      identification of subsets of prostate cancer cells of potentially high clinical
      relevance.

PMID- 23969937
TI  - The G-protein-coupled receptor CLR is upregulated in an autocrine loop with
      adrenomedullin in clear cell renal cell carcinoma and associated with poor
      prognosis.
AB  - PURPOSE: The G-protein-coupled receptor (GPCR) calcitonin receptor-like receptor
      (CLR) and its ligand peptide adrenomedullin (encoded by ADM gene) are implicated
      in tumor angiogenesis in mouse models but poorly defined in human cancers. We
      therefore investigated the diagnostic/prognostic use for CLR in human tumor types
      that may rely on adrenomedullin signaling and in clear cell renal cell carcinoma
      (RCC), a highly vascular tumor, in particular. EXPERIMENTAL DESIGN: In silico
      gene expression mRNA profiling microarray study (n = 168 tumors) and cancer
      profiling cDNA array hybridization (n = 241 pairs of patient-matched tumor/normal
      tissue samples) were carried out to analyze ADM mRNA expression in 13 tumor
      types. Immunohistochemistry on tissue microarrays containing patient-matched
      renal tumor/normal tissues (n = 87 pairs) was conducted to study CLR expression
      and its association with clinicopathologic parameters and disease outcome.
      RESULTS: ADM expression was significantly upregulated only in RCC and endometrial
      adenocarcinoma compared with normal tissue counterparts (P < 0.01). CLR was
      localized in tumor cells and vessels in RCC and upregulated as compared with
      patient-matched normal control kidney (P < 0.001). Higher CLR expression was
      found in advanced stages (P < 0.05), correlated with high tumor grade (P < 0.01)
      and conferred shorter overall survival (P < 0.01). CONCLUSIONS: In human tissues
      ADM expression is upregulated in cancer type-specific manner, implicating
      potential role for adrenomedullin signaling in particular in RCC, where CLR
      localization suggests autocrine/paracrine mode for adrenomedullin action within
      the tumor microenvironment. Our findings reveal previously unrecognized CLR
      upregulation in an autocrine loop with adrenomedullin in RCC with potential
      application for this GPCR as a target for future functional studies and drug
      development.

PMID- 23969938
TI  - Emergence of polyclonal FLT3 tyrosine kinase domain mutations during sequential
      therapy with sorafenib and sunitinib in FLT3-ITD-positive acute myeloid leukemia.
AB  - PURPOSE: To evaluate the clinical activity of sequential therapy with sorafenib
      and sunitinib in FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication
      (ITD)-positive acute myelogenous leukemia (AML) and monitor the emergence of
      secondary FLT3 tyrosine kinase domain (TKD) mutations during treatment.
      EXPERIMENTAL DESIGN: Six children with relapsed/refractory AML were treated with
      sorafenib in combination with clofarabine and cytarabine, followed by single
      agent sorafenib if not a candidate for transplantation. Sunitinib was initiated
      after sorafenib relapse. Bone marrow samples were obtained for assessment of FLT3
      TKD mutations by deep amplicon sequencing. The phase of secondary mutations with
      ITD alleles was assessed by cloning and sequencing of FLT3 exons 14 through 20.
      Identified mutations were modeled in Ba/F3 cells, and the effect of kinase
      inhibitors on FLT3 signaling and cell viability was assessed. RESULTS: Four
      patients achieved complete remission, but 3 receiving maintenance therapy with
      sorafenib relapsed after 14 to 37 weeks. Sunitinib reduced circulating blasts in
      two patients and marrow blasts in one. Two patients did not respond to sorafenib
      combination therapy or sunitinib. FLT3 mutations at residues D835 and F691 were
      observed in sorafenib resistance samples on both ITD-positive and -negative
      alleles. Deep sequencing revealed low-level mutations and their evolution during
      sorafenib treatment. Sunitinib suppressed leukemic clones with D835H and F691L
      mutations, but not D835Y. Cells expressing sorafenib-resistant FLT3 mutations
      were sensitive to sunitinib in vitro. CONCLUSIONS: Sunitinib has activity in
      patients that are resistant to sorafenib and harbor secondary FLT3 TKD mutations.
      The use of sensitive methods to monitor FLT3 mutations during therapy may allow
      individualized treatment with the currently available kinase inhibitors.

PMID- 23969939
TI  - Exploration and comparison of inborn capacity of aerobic and anaerobic
      metabolisms of Saccharomyces cerevisiae for microbial electrical current
      production.
AB  - Saccharomyces cerevisiae possesses numerous advantageous biological features,
      such as being robust, easily handled, mostly non-pathogenic and having high
      catabolic rates, etc., which can be considered as merits for being used as a
      promising biocatalyst in microbial fuel cells (MFCs) for electricity generation.
      Previous studies have developed efficient MFC configurations to convert metabolic
      electron shuttles, such as cytoplasmic NADH, into usable electric current.
      However, no studies have elucidated the maximum potential of S. cerevisiae for
      current output and the underlying metabolic pathways, resulting from the
      interaction of thousands of reactions inside the cell during MFC operation. To
      address these two key issues, this study used in silico metabolic engineering
      techniques, flux balance analysis (FBA), and flux variability analysis with
      target flux minimization (FATMIN), to model the metabolic perturbation of S.
      cerevisiae under the MFC-energy extraction. The FBA results showed that, in the
      cytoplasmic NADH-dependent mediated electron transfer (MET) mode, S. cerevisiae
      had a potential to produce currents at up to 5.781 A/gDW for the anaerobic and
      6.193 A/gDW for the aerobic environments. The FATMIN results showed that the
      aerobic and anaerobic metabolisms are resilient, relying on six and five
      contributing reactions respectively for high current production. Two reactions,
      catalyzed by glutamate dehydrogenase (NAD) (EC 1.4.1.3) and methylene
      tetrahydrofolate dehydrogenase (NAD) (EC 1.5.1.5), were shared in both current
      production modes and contributed to over 80% of the identified maximum current
      outputs. It is also shown that the NADH regeneration was much less energy costly
      than biomass production rate. Taken together, our finding suggests that S.
      cerevisiae should receive more research effort for MFC electricity production. 

PMID- 23969940
TI  - Nanocrystalline starch grafted palladium(II) complex for the Mizoroki-Heck
      reaction.
AB  - Nanocrystalline starch produced from the acid hydrolysis of gelatinized starch
      has been used for the first time to support palladium(II) ethylenediamine
      complex. The nanocrystalline starch supported Pd(II) complex was found to be an
      efficient and efficiently recycled catalyst for the Mizoroki-Heck reaction of
      furans and thiophenes with styrenes under mild reaction conditions.

PMID- 23969941
TI  - Style in science communication.
AB  - There is little doubt that during the past few decades science communication
      efforts aimed at non-expert audiences have increased in quantity and intensity on
      a global scale. Public engagement and outreach activities have now become a
      routine - when not a prominent - feature for several research institutions in
      Europe. However, it would be difficult for both scholars and those involved in
      science communication to agree on the impact of these activities, on the long
      term implications of the 'science communication movement' and on the indicators
      we should develop and employ in order to assess impact. The paper argues that
      quality is a relevant issue and challenge for contemporary science communication.
      Style is relevant to addressing that challenge, insofar as it relates to
      discussions about how to strengthen the quality of science communication,
      suggesting a different perspective other than the traditional
      normative/prescriptive framework. The notion of style also fruitfully connects
      the debate on science communication with a rich tradition of studies in the
      history and sociology of science. 

PMID- 23969942
TI  - A facile route to Si nanowire gate-all-around field effect transistors with a
      steep subthreshold slope.
AB  - We present a facile CMOS-compatible fabrication of lateral gate-all-around (GAA)
      field effect transistors (FETs) based on concentric Si-SiO2/N(++)Si core-multi
      shell nanowires (NWs). Si-SiO2/N(++)Si core-multi-shell NWs were prepared by
      sequential Si NW growth, thermal oxidation and Si deposition processes in a
      single chamber. The GAA NW FET was then fabricated using the Si core, SiO2 inner
      shell, N(++) Si outer-shell as a channel, gate dielectric, and gate electrode,
      respectively. A one-step wet etching process was able to define the gate and
      source-drain contact regions. The SiNW GAA FET clearly exhibits a geometry
      dependent gating effect and a steep subthreshold slope due to the low interface
      trapped charge density at the interface of the Si core and the SiO2 shell. Our
      proposed SiNW GAA structures offer new opportunities for low-energy-consumption
      digital device applications.

PMID- 23969943
TI  - Chondrogenic differentiation of human umbilical cord blood-derived mesenchymal
      stem cells by co-culture with rabbit chondrocytes.
AB  - The objective of the current study was to investigate the ability of human
      umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) to undergo
      chondrogenic differentiation, by co-culture with rabbit chondrocytes. The aim was
      to obtain more seed cells for tissue engineering research and lay the foundation
      for the clinical repair of cartilage defects. The studies were performed using
      isolated rabbit cartilage cells and HUCB-MSCs in vitro, which were co-cultured in
      a 2:1 or 3:1 ratio with or without insulin-like growth factor-1 (IGF-1).
      Following 7 and 14 days in culture, cell morphology was observed in each group.
      RNA and protein were extracted to assess the expression levels of aggrecan (ACAN)
      and collagen type II (COL2A) using quantitative polymerase chain reaction (qPCR)
      and western blotting, respectively. Groups of cells that were co-cultured
      exhibited significantly higher expression levels of ACAN and COL2A mRNA and
      protein, compared with the reduced effect of IGF-1 at days 7 and 14 in culture.
      The addition of IGF-1 was found to potentiate these effects. Specifically, at day
      7, cells co-cultured at a ratio of 2:1 had a greater induction of ACAN and COL2A
      compared with cells co-cultured at a 3:1 ratio. However, following 14 days
      culture, cells co-cultured at a 3:1 ratio with additional IGF-1 exhibited a
      greater induction of ACAN and COL2A compared with cells co-cultured at a ratio of
      2:1. Human chondrocytes may be successfully induced by co-culture of HUCB-MSCs
      with rabbit chondrocytes, thus providing a theoretical basis to obtain seed cells
      with the capacity to differentiate into multiple cell types, with low
      immunogenicity. Notably, these cells may provide a valuable resource for tissue
      engineering.

PMID- 23969945
TI  - High expression of trimethylated histone H3 at lysine 27 predicts better
      prognosis in non-small cell lung cancer.
AB  - Epigenetic parameters such as DNA methylation and histone modifications play
      pivotal roles in carcinogenesis. Global histone modification patterns have been
      implicated as possible predictors of cancer recurrence and prognoses in a great
      variety of tumor entities. Our study was designed to evaluate the association
      among trimethylated histone H3 at lysine 27 (H3K27me3), clinicopathological
      variables and outcome in early-stage non-small cell lung cancer (NSCLC). The
      expression of H3K27me3 and its methyl-transferase, enhancer of zeste homolog 2
      (EZH2) together with proliferating cell nuclear antigen (PCNA) were evaluated by
      immunohistochemistry in normal lung tissue (n=5) and resected NSCLC patients
      (n=42). In addition, the specificity of antibody for H3K27me3 was tested by
      western blot analysis. The optimal cut-off point of H3K27me3 expression for
      prognosis was determined by the X-tile program. The prognostic significance was
      determined by means of Kaplan-Meier survival estimates and log-rank tests. As a
      result, enhanced trimethylation of H3K27me3 was correlated with longer overall
      survival (OS) and better prognosis (P<0.05). Moreover, both univariate and
      multivariate analyses indicated that H3K27me3 level was a significant and
      independent predictor of better survival (hazard ratio, 0.187; 95% confidence
      interval, 0.066-0.531, P=0.002). Furthermore, H3K27me3 expression was positively
      correlated with DNA methylation level at CCGG sites while reversely related to
      EZH2 expression (P<0.05). In conclusion, H3K27me3 level defines unrecognized
      subgroups of NSCLC patients with distinct epigenetic phenotype and clinical
      outcome, and can probably be used as a novel predictor for better prognosis in
      NSCLC patients.

PMID- 23969946
TI  - What holds paper together: nanometre scale exploration of bonding between paper
      fibres.
AB  - Paper, a man-made material that has been used for hundreds of years, is a network
      of natural cellulosic fibres. To a large extent, it is the strength of bonding
      between these individual fibres that controls the strength of paper. Using atomic
      force microscopy, we explore here the mechanical properties of individual fibre
      fibre bonds on the nanometre scale. A single fibre-fibre bond is loaded with a
      calibrated cantilever statically and dynamically until the bond breaks. Besides
      the calculation of the total energy input, time dependent processes such as creep
      and relaxation are studied. Through the nanometre scale investigation of the
      formerly bonded area, we show that fibrils or fibril bundles play a crucial role
      in fibre-fibre bonding because they act as bridging elements. With this
      knowledge, new fabrication routes can be deduced to increase the strength of an
      ancient product that is in fact an overlooked high-tech material. 

PMID- 23969947
TI  - Eicosanoids and docosanoids in plasma and aorta of healthy and atherosclerotic
      rabbits.
AB  - Eicosanoids and docosanoids have been shown to be involved in atherosclerosis.
      Polyunsaturated fatty acids (PUFAs) are important nutrients that are metabolized
      by lipoxygenases and cyclooxygenases to various mono-hydroxy metabolites which
      can be further metabolized by specific enzymes to more complex eicosanoids and
      docosanoids. In this study a high-performance liquid chromatography methodology
      was established and rabbits were fed with a control or a high-cholesterol diet to
      induce atherosclerotic lesions to determine pro- or anti-inflammatory lipid
      mediators in atherosclerotic vessels. In aortic samples from atherosclerotic
      rabbits we determined for the first time various eicosanoids/docosanoids and
      observed an increased concentration of 12-lipoxygenase metabolites. Increased
      levels of 12-hydroxyeicosatetraenoic acid (12-HETE) in high-cholesterol versus
      control animals as well as increased ratios of 12-HETE/arachidonic acid ratios
      indicate that 12-lipoxygenase metabolites may have importance in atherosclerosis.
      In addition, decreased concentrations of the 5-lipoxygenase metabolite
      leukotriene B4 levels were detected in high-cholesterol animals. A positive
      correlation of total plaque area with plasma levels of 12-HETE and a negative
      correlation with aortic levels of endogenous PPARgamma-ligand 13-oxo
      octadecadienoic acid were found. This study let us conclude that the cholesterol
      content in the diet might influence atherosclerosis via increased 12-lipoxygenase
      and cyclooxygenase-mediated pathways and reduced 5-lipoxygenase pathways. 

PMID- 23969949
TI  - Effect of temozolomide in patients with metastatic bronchial carcinoids.
AB  - INTRODUCTION: Metastatic bronchial carcinoids are rare neoplasms, where efforts
      of medical treatment so far have been disappointing. A previous study from our
      center indicated that temozolomide might be of value. MATERIALS AND METHODS: All
      patients with progressive metastatic bronchial carcinoid treated with
      temozolomide as monotherapy at our center between 2004 and 2010 (n = 31) were
      included in this retrospective study. 14 tumors were classified as typical and 15
      as atypical carcinoids, whereas 2 tumors could not be classified. Temozolomide
      was given on 5 consecutive days every 4 weeks. Toxicity was evaluable in 28 of 31
      patients, and 22 patients were evaluable by RECIST 1.1. RESULTS: There were no
      complete responses. A partial response was seen in 3 patients (14%), stable
      disease in 11 (52%) and progressive disease in 7 patients (33%). Median
      progression-free survival was 5.3 months and median overall survival was 23.2
      months from the start of temozolomide. Toxicities grade 3-4 were noted in 4
      patients, thrombocytopenia (n = 3) and leukopenia (n = 1). CONCLUSION:
      Temozolomide as monotherapy shows activity in metastatic bronchial carcinoids.
      Regimens combining temozolomide with other agents (e.g. capecitabine and/or
      bevacizumab, everolimus, radiolabeled somatostatin analogues) should be further
      studied in these patients.

PMID- 23969950
TI  - Adenovirus-mediated ING4 expression reduces multidrug resistance of human gastric
      carcinoma cells in vitro and in vivo.
AB  - Chemotherapy is the primary treatment for both resectable and advanced gastric
      carcinoma, yet multiple drug resistance (MDR) of gastric carcinoma remains a
      significant therapeutic obstacle. The development of novel strategies to reduce
      MDR in gastric carcinoma would yield a better outcome following chemotherapy.
      ING4, a member of the inhibitor of growth (ING) tumor-suppressor family,
      possesses antitumor and radiosensitization or chemosensitization effects in a
      variety of human cancers. The present study investigated the effects and possible
      mechanisms of action of adenovirus-mediated ING4 (AdVING4) on the reversion of
      human gastric carcinoma cell MDR in vitro and in vivo in nude mouse xenografts.
      The data showed that the expression of ING4 mRNA and protein was dramatically
      downregulated (or lost) in gastric carcinoma SGC7901/CDDP cells after CDDP
      induced MDR phenotype and in the parental SGC7901 cells. AdVING4-induced ING4
      expression reversed MDR and induced apoptosis of SGC7901/CDDP cells in vitro and
      in vivo in the SGC7901/CDDP xenograft tumors. Furthermore, AdVING4 substantially
      downregulated the expression of MDR-related proteins P-gp and MRP1 and apoptosis
      related proteins Bcl-2 and survivin, but upregulated the expression of apoptosis
      related protein Bax in the SGC7901/CDDP xenograft tissues. The reversion effects
      elicited by AdVING4 on gastric cancer cell MDR were closely associated with the
      downregulation of ATP-binding cassette transporters and activation of apoptotic
      pathways. Thus, these findings suggest that AdVING4 may be a feasible modulator
      for the MDR phenotype of gastric carcinoma cells. 

PMID- 23969951
TI  - Characteristic testicular histology is useful for the identification of NR5A1
      gene mutations in prepubertal 46,XY patients.
AB  - BACKGROUND: Individuals with NR5A1 mutations encoding steroidogenic factor-1
      (SF1) develop a phenotypically broad range of disorders of sexual development
      (DSD). Based on a literature review, we noted that hypoplastic seminiferous
      tubules and the emergence of Leydig cells with vacuolar cytoplasms are seen
      predominantly in the majority of individuals with NR5A1 mutations. AIM: The aim
      of this study was to address whether the histopathological characteristics of the
      testis can be a biomarker for 46,XY individuals with NR5A1 mutations. DESIGN: In
      order to ascertain whether or not the histological features were the
      characteristics of NR5A1 mutations, we screened the testicular histology of 242
      patients with 46,XY DSD and then subsequently assessed NR5A1 mutations. RESULT:
      Of 242 patients with 46,XY DSD, 6 patients matched histological testicular
      features: a reduced number of thin seminiferous tubules and focal aggregations of
      Leydig cells that contained cytoplasmic lipid droplets. All 6 patients had NR5A1
      mutations. These histological features were distinct from those of other DSD.
      Thus, this unique testicular histology is useful for identifying NR5A1 mutations
      in 46,XY patients with DSD before puberty.

PMID- 23969952
TI  - Internal carotid artery variations in velocardiofacial syndrome patients and its
      implications for surgery.
AB  - BACKGROUND: Medially displaced internal carotid arteries in velocardiofacial
      syndrome carry a risk during pharyngeal flap surgery. This study was designed to
      evaluate the frequency of medially deviated internal carotid arteries in both
      velocardiofacial syndrome patients and the general pediatric population and to
      assess the minimum distance to the pharyngeal walls to define the potential risk
      of internal carotid artery injury during pharyngeal surgery. METHODS: Twenty
      three consecutive patients with velocardiofacial syndrome who underwent posterior
      pharyngeal flap surgery and 21 control subjects who did not have velocardiofacial
      syndrome but who underwent oropharynx magnetic resonance imaging were reviewed.
      RESULTS: Medial deviation of at least one internal carotid artery was documented
      in 10 velocardiofacial syndrome patients (43.5 percent), compared with three
      patients (14.3 percent) in the control group (p=0.034). The mean+/-SD minimum
      distance to the posterior pharyngeal wall was 3.78+/-1.86 mm in velocardiofacial
      syndrome patients and 9.17+/-2.94 mm in the control group (p=0.014). Only one
      patient had significant medial dislocation of the internal carotid artery, and
      the closest distance from the pharyngeal wall was 0.86 mm. CONCLUSIONS: In
      velocardiofacial syndrome patients, medial dislocation of the internal carotid
      artery was common, and the minimum distance to the pharyngeal wall was short
      compared with the control group. However, in most of the authors' patients, the
      course of the cervical portion of the internal carotid artery is irrelevant to
      pharyngeal flap surgery. The authors conclude that preoperative vascular imaging
      study is not cost-effective in velocardiofacial syndrome patients but that
      intraoperative use of ultrasound imaging is still valuable for the purpose of
      planning pharyngeal flap surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

PMID- 23969953
TI  - Randomised in situ study on the efficacy of a tin/chitosan toothpaste on erosive
      abrasive enamel loss.
AB  - Tin is a notable anti-erosive agent, and the biopolymer chitosan has also shown
      demineralisation-inhibiting properties. Therefore, the anti-erosive/anti-abrasive
      efficacy of the combination of both compounds was tested under in situ
      conditions. Twenty-seven volunteers were included in a randomised, double-blind,
      three-cell crossover in situ trial. Enamel specimens were recessed on the buccal
      aspects of mandibular appliances, extraorally demineralised (6 * 2 min/day) and
      intraorally treated with toothpaste slurries (2 * 2 min/day). Within the slurry
      treatment time, one-half of the specimens received additional intraoral brushing
      (5 s, 2.5 N). The tested toothpastes included a placebo toothpaste, an
      experimental NaF toothpaste (1,400 ppm F(-)) and an experimental F/Sn/chitosan
      toothpaste (1,400 ppm F(-), 3,500 ppm Sn(2+), 0.5% chitosan). The percentage
      reduction of tissue loss (slurry exposure/slurry exposure + brushing) compared to
      placebo was 19.0 +/- 47.3/21.3 +/- 22.4 after use of NaF and 52.5 +/- 30.9/50.2
      +/- 34.3 after use of F/Sn/chitosan. F/Sn/chitosan was significantly more
      effective than NaF (p <= 0.001) and showed good efficacy against erosive and
      erosive-abrasive tissue loss. This study suggests that the F/Sn/chitosan
      toothpaste could provide good protection for patients who frequently consume
      acidic foodstuffs. 

PMID- 23969954
TI  - Ncking BCR-mediated PI3K activation.

PMID- 23969956
TI  - Compounding for pediatric patients: case reports and formulations.
AB  - When no commercially available agent is appropriate for a pediatric patient, a
      compounded formulation often assures successful treatment. In the following case
      reports of five children, a pharmaceutical compound is an essential component of
      long-term therapy for a disorder best managed with customized medications and
      supplements. 

PMID- 23969955
TI  - Mammalian iRhoms have distinct physiological functions including an essential
      role in TACE regulation.
AB  - Loss of iRhom2, a catalytically inactive rhomboid-like protein, blocks maturation
      of TACE/ADAM17 in macrophages, resulting in defective shedding of the cytokine
      tumor necrosis factor. Apart from the resulting inflammatory defects, iRhom2-null
      mice appear normal: they do not show the several defects seen in TACE knockouts,
      suggesting that TACE maturation is independent of iRhom2 in cells other than
      macrophages. Here we show that the physiological role of iRhoms is much broader.
      iRhom1 knockout mice die within 6 weeks of birth. They show a severe phenotype,
      with defects in several tissues including highly penetrant brain haemorrhages.
      The non-overlapping phenotypes imply that iRhom 1 and 2 have distinct
      physiological roles, although at a cellular level both promote the maturation of
      TACE (but not other ADAM proteases). Both iRhoms are co-expressed in many
      contexts where TACE acts. We conclude that all TACE activity, constitutive and
      regulated, requires iRhom function. iRhoms are therefore essential and specific
      regulators of TACE activity, but our evidence also implies that they must have
      additional physiologically important clients. 

PMID- 23969957
TI  - Evaluation of dosage form information provided in pediatric drug trial reports.
AB  - This report is the first to replicate the earlier findings of Standing et al and
      validates the inadequacy of reporting of dosage forms used in pediatric drug
      trials. Journal authors should provide and journal editors should require
      adequate dosage form information for published reports of pediatric drug trials.
      We also recommend that compounding pharmacists provide detailed compounding
      instructions to assure that extemporaneously compounded formulations can be
      reliably reproduced, and that quality-control data be provided to support
      formulation stability. Until the problem of insufficient information is
      addressed, replication of many pediatric drug trials is impossible, calling into
      question their reliability and validity. 

PMID- 23969958
TI  - Compounding for manufacturer backorders and discontinuations: "oh no! Not
      again!".
AB  - Drug shortages due to manufacturer backorders and discontinuations are a concern
      and frustration for pharmacists, physicians, and patients. Keeping up-to-date on
      the latest shortages, utilizing good key references, and using compounding as an
      alternative source for the drugs can keep the patients on their current therapy
      that is optimum for them. This article discusses some of the factors that
      influence drug supplies, provides some of the resources to find information on
      backordered or discontinued drugs, and provides some formulations as alternatives
      to backordered or discontinued medications. 

PMID- 23969959
TI  - Compounding with sucralfate for the treatment of external wounds.
AB  - Sucralfate was originally marketed for the prevention and accelerated healing of
      duodenal ulcers. Physicians also have used sucralfate in the treatment of ulcers
      and erosions in the mouth, esophagus, and stomach, although its effectiveness in
      these areas has never been clearly proven. This article discusses the use and
      effectiveness of sucralfate in the treatment of external wounds. The author
      provides case reports as support for sucralfate's success in treating wounds and
      provides formulations for the unconventional use of this drug. The author has
      found sucralfate to be relatively inexpensive and inert when compared to other
      ingredients, and has found sucralfate to be very versatile and capable of healing
      almost any wound. 

PMID- 23969960
TI  - Identifying the criteria of a valid stability study.
AB  - The objective of a stability study is to establish specifications for the storage
      of a drug substance or active ingredient, and to esure that the correct beyond
      use date is assigned by demonstrating stability throughout its shelf life.
      Certain criteria must be met for a study to be considered a valid stability
      study. The purpose of this article is to clarify the criteria for a valid
      stability study so compounding pharmacists will understand what to look for when
      reviewing a stability study to determine an appropriate beyond-use date for
      compounded preparations. 

PMID- 23969961
TI  - Summertime in an American apothecary garden.
AB  - During the mid-15th century and into the 16th and 17th centuries, bound copies or
      herbals emerged in Europe as part of classical educations. From the records by
      medieval monks, Greek texts, Islamic records, German herbals, and books of French
      remedies, a translation into English was printed in 1577. Garden designs and
      herbals provided guidance about planting artistically and elaborately, which
      provided Europeans an opportunity to develop awareness about medical and
      botanical investigation. Members of the healing professions recognized that
      accurate plant identification from medicinal gardens was essential for the sick
      to be consistently treated. From medicinals in the New World and specimens
      imported by explorers, the medicinal garden, with accompanying collection and
      dispensing notes, emerged in Colonial America. In 2005, a contemporary American
      demonstration apothecary garden was established in conjunction with the Oklahoma
      Pharmacy Museum located in Guthrie, Oklahoma. The project was sponsored by the
      Foundation of the Oklahoma Pharmaceutical Association and citizens of the
      Historic District of Guthrie, so desginated by the U.S. Department of the
      Interior. This article reviews the structure, landscaping, and plantings of a
      newly designed apothecary garden. 

PMID- 23969962
TI  - Compounding for cancer in companion animals: therapeutic options and case
      reports.
AB  - Americans spend more than $20 billion per year on health care for their pets
      which are considered by many owners to be members of the family. In the past, the
      diagnosis of cancer in a companion animal could be considered a death sentence,
      but today, drugs designed for use in human patients offer a good quality of life
      and extended survival for many veterinary cancer patients. Often, the key to the
      success of that treatment is compounding, in which doses of manufactured drugs
      that would prove toxic to a cat or dog are reformulated into appropriate strenths
      or concentrations that provide beneficial therapy. In this article, two case
      reports describe the use of anticancer agents in dogs, and formulations for the
      compounding of several antineoplastic agents for veterinary patients are
      presented. 

PMID- 23969963
TI  - Technology for the compounding pharmacy: digital pens-tools or toys?
AB  - Compounding pharmcists should consider technology that would improve the safety
      and effectiveness of patients' compounded preparations. Selecting and
      appropriately implementing technology that also is relatively inexpensive,
      practical, improves workflow, and stays within the comfort range of employees
      makes such selections worthwhile. This article discusses the various types of
      digital pens and their use within a compounding pharmacy. 

PMID- 23969964
TI  - Quality-control analytical methods: testing of electrolytes solutions.
AB  - Electrolyte balance in humans is regulated by various homeostatic mechanisms.
      Electrolytes disturbances can be restored with oral or parenteral supplements, as
      well as in parenteral nutrition solutions. Multiple electrolytes injections are
      sterile preparations, and quality-control testing for these solutions follows the
      extablished guidelines in current United States Pharmacopeial monographs
      published in the United States Pharmacopeia. 

PMID- 23969965
TI  - Basics of compounding: considerations for implementing United States pharmacopeia
      chapter 797 pharmaceutical compounding-sterile preparations, part 11.
AB  - Total patient care necessitates the use of hazardous drugs in the compounding of
      preparations. With approximately 5.5 million U.S. healthcare workers potentially
      being exposed to hazardous drugs, the importance and necessity of a pharmacy
      establishing and maintaining standard operating procedures pertaining to the
      handling of hazardous drugs cannot be minimized. This article defines hazardous
      drugs, discusses many of the factors that impact worker exposure, identifies many
      of the sources of exposure, identifies the four general goals for handling
      hazardous drugs, discusses the proper handling and disposal of hazardous drug
      waste materials, and provides a checklist that can be used by a pharmacy to
      establish protocols for a hazardous drug program. 

PMID- 23969966
TI  - Testing of estradiol in a compounded cream and a stock solution.
AB  - Potency testing (i.e., analysis of the concentration of the active ingredient) is
      an important part of the quality-control process for compounded preparations.
      However, concerns about the reliability and interpretation of potency testing
      results have been raised by compounding professionals. Standards detailed in
      United States Pharmacopeia Chapter 795 allow nonsterile preparations to be within
      90% to 110% of the theoretical calculated and labeled quantity of active
      ingredient. Variability among independent testing laboratories could have
      significant implications for interpretaion of whether a compounded preparation
      meets these standards. The primary goal of this study was to characterize the
      variability among analytical testing laboratories when analyzing the potency of a
      nonsterile, compounded hormone cream (specifically, estradiol) and an estradiol
      stock solution used to compound the cream. Blinded to the theoretical
      concentration of the active ingredient, three analytical testing labs were sent
      samples and asked to determine the concentration and the percent potency in the
      samples. The stock solution samples were sent after the results for the cream
      were received. All three labs found the hormone cream to be within the acceptable
      Unied States Pharmacopeia range of 90% to 110%. Percent potency ranged from 95%
      to 103.1%, with an average of 98.5% +/- 4.2%. All labs also found the stock
      solution to be within acceptable United States Pharmacopeia range. The labs found
      an average of 6.21 +/- 0.24 mg/mL estradiol. The average difference between the
      lab and the theoretical concentration was 0.21 +/- 0.24 mg/mL. Percent potency
      ranged from 100% to 107.8%, with an average of 103.4% +/- 4.0%. This study found
      a variability of about 4% among labs when analyzing the same nonsterile
      compounded estradiol homrone cream. The magnitude of these variations was
      consistent when estradiol was combined with other ingredients in a compounded
      cream and when it was analyzed as a stock solution. Between-lab variability must
      be considered when interpreting whether a pharmacy's compounded preparation is
      within the United States Pharmacopeia potency critera. 

PMID- 23969967
TI  - Compatibility and stability of palonosetron hydrochloride and propofol during
      simulated y-site administration.
AB  - Palonosetron hydrochloride is a longer-acting, selective 5-HT3 receptor
      antagonist that has been approved for prevention of chemotherapy-induced nausea
      and vomiting and is being evaluated for prevention of postoperative nause and
      vomiting. The objective of this study was to evaluate the physical and chemical
      stablity of palonosetron hydrochloride 50 mcg/mL when mixed with undiluted
      propofol 1% during simulated Y-site administation. Duplicate samples of this
      mixture were tested. Samples were stored and evaluated for up to 4 hours at room
      temperature. Physical stability was assessed by visual inspection. Chemical
      stability was assessed by high-performance liquid chromatographic analysis. All
      of the admixtures were opaque white when viewed in normal fluorescent room light
      and when viewed with a Tyndall beam. After centrifugation, no evidence of
      precipitation was found. The drug concentrations were essentially unchanged in
      all of the samples throughout the study. Palonosetron hydrochloride is physically
      and chemically stable when mixed with propofol as undiluted injections during
      simulated Y-site administration over 4 hours at ambient room temperature. 

PMID- 23969968
TI  - The value of near infrared spectroscopy in a small hospital compounding unit to
      control the risks associated with raw materials.
AB  - Pharmaceutical products, including capsules, oral suspensions, and solutions, are
      prepared by hospital pharmacists if no commercial product is available.
      Identification of the raw materials is a regulatory requirement before
      manufacturing (compounding). Because of the standard methods used, however, this
      is often time-consuming and laborious in a hospital setting. This article
      describes the use of near infrared spectroscopy in combination with chemometric
      methods for discrimination of raw materials. Sixty-three pulverized powder
      samples were discriminated by using reference samples (identity guaranteed by
      supplier and confirmed by mid infrared analyses) and NIRCal cluster analyses. A
      routine expert application involving optimized calibrations (n=6) was developed,
      which allowed a rapid and nondestructive release procedure for every powder-based
      raw material received. This technique is superior to established identification
      analyses because of reduced quarantine times and cost savings. 

PMID- 23969969
TI  - Postscription: The Compounding Pharmacy in Brazil: A Pharmacist's Perspective.
AB  - This is the first of a series of articles from compounders from around the world
      who explain their perspective on compounding pharmacy within their country. In
      this article, the authors have provided a brief synopsis of compounding pharmacy
      in Brazil. 

PMID- 23969970
TI  - Aligned carbon nanotubes: from controlled synthesis to electronic applications.
AB  - Single-wall carbon nanotubes (SWNTs) possess superior geometrical, electronic,
      chemical, thermal, and mechanical properties and are very attractive for
      applications in electronic devices and circuits. To make this a reality, the
      nanotube orientation, density, diameter, electronic property, and even chirality
      should be well controlled. This Feature article focuses on recent achievements
      researchers have made on the controlled growth of horizontally aligned SWNTs and
      SWNT arrays on substrates and their electronic applications. Principles and
      strategies to control the morphology, structure, and properties of SWNTs are
      reviewed in detail. Furthermore, electrical properties of field-effect
      transistors fabricated on both individual SWNTs and aligned SWNT arrays are
      discussed. State-of-the-art electronic devices and circuits based on aligned
      SWNTs and SWNT arrays are also highlighted. 

PMID- 23969971
TI  - Early responses of the STAT3 pathway to platinum drugs are associated with
      cisplatin resistance in epithelial ovarian cancer.
AB  - Cisplatin resistance remains one of the major obstacles when treating epithelial
      ovarian cancer. Because oxaliplatin and nedaplatin are effective against
      cisplatin-resistant ovarian cancer in clinical trials and signal transducer and
      activator of transcription 3 (STAT3) is associated with cisplatin resistance, we
      investigated whether overcoming cisplatin resistance by oxaliplatin and
      nedaplatin was associated with the STAT3 pathway in ovarian cancer. Alamar blue,
      clonogenic, and wound healing assays, and Western blot analysis were used to
      compare the effects of platinum drugs in SKOV-3 cells. At an equitoxic dose,
      oxaliplatin and nedaplatin exhibited similar inhibitory effects on colony-forming
      ability and greater inhibition on cell motility than cisplatin in ovarian cancer.
      Early in the time course of drug administration, cisplatin increased the
      expression of pSTAT3 (Tyr705), STAT3alpha, VEGF, survivin, and Bcl-XL, while
      oxaliplatin and nedaplatin exhibited the opposite effects, and upregulated pSTAT3
      (Ser727) and STAT3beta. The STAT3 pathway responded early to platinum drugs
      associated with cisplatin resistance in epithelial ovarian cancer and provided a
      rationale for new therapeutic strategies to reverse cisplatin resistance.

PMID- 23969972
TI  - Effect of ozone oxidative preconditioning in preventing early radiation-induced
      lung injury in rats.
AB  - Ionizing radiation causes its biological effects mainly through oxidative damage
      induced by reactive oxygen species. Previous studies showed that ozone oxidative
      preconditioning attenuated pathophysiological events mediated by reactive oxygen
      species. As inhalation of ozone induces lung injury, the aim of this study was to
      examine whether ozone oxidative preconditioning potentiates or attenuates the
      effects of irradiation on the lung. Rats were subjected to total body
      irradiation, with or without treatment with ozone oxidative preconditioning (0.72
      mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and
      histopathological analysis were compared at 6 and 72 h after total body
      irradiation. Irradiation significantly increased lung malondialdehyde levels as
      an end-product of lipoperoxidation. Irradiation also significantly decreased lung
      superoxide dismutase activity, which is an indicator of the generation of
      oxidative stress and an early protective response to oxidative damage. Ozone
      oxidative preconditioning plus irradiation significantly decreased
      malondialdehyde levels and increased the activity of superoxide dismutase, which
      might indicate protection of the lung from radiation-induced lung injury. Serum
      tumor necrosis factor alpha and interleukin-1 beta levels, which increased
      significantly following total body irradiation, were decreased with ozone
      oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to
      ameliorate radiation-induced lung injury assessed by histopathological
      evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose
      intraperitoneal administration of ozone, did not exacerbate radiation-induced
      lung injury, and, on the contrary, it provided protection against radiation
      induced lung damage. 

PMID- 23969973
TI  - Thalamic metabolic abnormalities in patients with Huntington's disease measured
      by magnetic resonance spectroscopy.
AB  - Huntington's disease (HD) is a neurologic disorder that is not completely
      understood; its fundamental physiological mechanisms and chemical effects remain
      somewhat unclear. Among these uncertainties, we can highlight information about
      the concentrations of brain metabolites, which have been widely discussed.
      Concentration differences in affected, compared to healthy, individuals could
      lead to the development of useful tools for evaluating the progression of
      disease, or to the advance of investigations of different/alternative treatments.
      The aim of this study was to compare the thalamic concentration of metabolites in
      HD patients and healthy individuals using magnetic resonance spectroscopy. We
      used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135
      ms. Spectra from 40 adult HD patients and 26 control subjects were compared.
      Quantitative analysis was performed using the LCModel method. There were
      statistically significant differences between HD patients and controls in the
      concentrations of N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test,
      P<0.001), and glycerophosphocholine+phosphocholine (GPC+PCh; t-test, P=0.001)
      relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was
      decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with
      controls. There were no correlations between the concentration ratios and
      clinical features. Although these results could be caused by T1 and T2 changes,
      rather than variations in metabolite concentrations given the short repetition
      time and long echo time values used, our findings point to thalamic dysfunction,
      corroborating prior evidence.

PMID- 23969975
TI  - Characterization of bacteriophages infecting clinical isolates of Pseudomonas
      aeruginosa stored in a culture collection.
AB  - Some clinical isolates of Pseudomonas aeruginosa stored in our culture collection
      did not grow or grew poorly and showed lysis on the culture plates when removed
      from the collection and inoculated on MacConkey agar. One hypothesis was that
      bacteriophages had infected and killed those clinical isolates. To check the best
      storage conditions to maintain viable P. aeruginosa for a longer time, clinical
      isolates were stored at various temperatures and were grown monthly. We
      investigated the presence of phage in 10 clinical isolates of P. aeruginosa
      stored in our culture collection. Four strains of P. aeruginosa were infected by
      phages that were characterized by electron microscopy and isolated to assess
      their ability to infect. The best condition to maintain the viability of the
      strains during storage was in water at room temperature. Three Siphoviridae and
      two Myoviridae phages were visualized and characterized by morphology. We
      confirmed the presence of bacteriophages infecting clinical isolates, and their
      ability to infect and lyse alternative hosts. Strain PAO1, however, did not show
      lysis to any phage. Mucoid and multidrug resistant strains of P. aeruginosa
      showed lysis to 50% of the phages tested.

PMID- 23969974
TI  - The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced
      gastric damage in rats.
AB  - Our objective was to investigate the protective effect of Lawesson's reagent, an
      H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were
      pretreated with saline or Lawesson's reagent (3, 9, or 27 umol/kg, po) once daily
      for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg)
      administration by gavage. On the last day of treatment, the animals were killed 4
      h after ALD administration. Gastric lesions were measured using a computer
      planimetry program, and gastric corpus pieces were assayed for malondialdehyde
      (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)
      alpha and interleukin (IL)-1beta], and myeloperoxidase (MPO). Other groups were
      pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg,
      ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 umol/kg Lawesson's reagent was
      administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric
      damage (63.35 +/- 9.8 mm(2)); increased levels of TNF-alpha, IL-1beta, and MDA
      (2311 +/- 302.3 pg/mL, 901.9 +/- 106.2 pg/mL, 121.1 +/- 4.3 nmol/g,
      respectively); increased MPO activity (26.1 +/- 3.8 U/mg); and reduced GSH levels
      (180.3 +/- 21.9 ug/g). ALD also increased cystathionine-gamma-lyase
      immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27
      umol/kg) attenuated ALD-mediated gastric damage (15.77 +/- 5.3 mm(2)); reduced
      TNF-alpha, IL-1beta, and MDA formation (1502 +/- 150.2 pg/mL, 632.3 +/- 43.4
      pg/mL, 78.4 +/- 7.6 nmol/g, respectively); lowered MPO activity (11.7 +/- 2.8
      U/mg); and increased the level of GSH in the gastric tissue (397.9 +/- 40.2
      ug/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's
      reagent. However, glibenclamide plus diazoxide did not alter the effects of
      Lawesson's reagent. Our results suggest that Lawesson's reagent plays a
      protective role against ALD-induced gastric damage through mechanisms that depend
      at least in part on activation of ATP-sensitive potassium (KATP) channels.

PMID- 23969976
TI  - Ziyuglycoside II-induced apoptosis in human gastric carcinoma BGC-823 cells by
      regulating Bax/Bcl-2 expression and activating caspase-3 pathway.
AB  - Ziyuglycoside II is an active compound of Sanguisorba officinalis L. that has
      anti-inflammation, antioxidation, antibiosis, and homeostasis properties. We
      report here on the anticancer effect of ziyuglycoside II on human gastric
      carcinoma BGC-823 cells. We investigated the effects of ziyuglycoside II on cell
      growth, cell cycle, and cell apoptosis of this cell line. Our results revealed
      that ziyuglycoside II could inhibit the proliferation of BGC-823 cells by
      inducing apoptosis but not cell cycle arrest, which was associated with
      regulation of Bax/Bcl-2 expression, and activation of the caspase-3 pathway. Our
      study is the first to report the antitumor potential of ziyuglycoside II in BGC
      823 gastric cancer cells. Ziyuglycoside II may become a potential therapeutic
      agent against gastric cancer in the future.

PMID- 23969977
TI  - Culture of bovine ovarian follicle wall sections maintained the highly estrogenic
      profile under basal and chemically defined conditions.
AB  - Follicle cultures reproduce in vitro the functional features observed in vivo. In
      a search for an ideal model, we cultured bovine antral follicle wall sections
      (FWS) in a serum-free defined medium (DM) known to induce 17beta-estradiol (E2)
      production, and in a nondefined medium (NDM) containing serum. Follicles were
      sectioned and cultured in NDM or DM for 24 or 48 h. Morphological features were
      determined by light microscopy. Gene expression of steroidogenic enzymes and
      follicle-stimulating hormone (FSH) receptor were determined by RT-PCR;
      progesterone (P4) and E2 concentrations in the media were measured by
      radioimmunoassay. DM, but not NDM, maintained an FWS morphology in vitro that was
      similar to fresh tissue. DM also induced an increase in the expression of all
      steroidogenic enzymes, except FSH receptor, but NDM did not. In both DM and NDM,
      there was a gradual increase in P4 throughout the culture period; however, P4
      concentration was significantly higher in NDM. In both media, E2 concentration
      was increased at 24 h, followed by a decrease at 48 h. The E2:P4 ratio was higher
      in DM than in NDM. These results suggest that DM maintains morphological
      structure, upregulates the expression of steroidogenic enzyme genes, and
      maintains steroid production with a high E2:P4 ratio in FWS cultures.

PMID- 23969978
TI  - Limb immobilization alters functional electrophysiological parameters of sciatic
      nerve.
AB  - Immobilization, used in clinical practice to treat traumatologic problems, causes
      changes in muscle, but it is not known whether changes also occur in nerves. We
      investigated the effects of immobilization on excitability and compound action
      potential (CAP) and the ultrastructure of the rat sciatic nerve. Fourteen days
      after immobilization of the right leg of adult male Wistar rats (n=34), animals
      were killed and the right sciatic nerve was dissected and mounted in a moist
      chamber. Nerves were stimulated at a baseline frequency of 0.2 Hz and tested for
      2 min at 20, 50, and 100 Hz. Immobilization altered nerve excitability. Rheobase
      and chronaxy changed from 3.13 +/- 0.05 V and 52.31 +/- 1.95 us (control group,
      n=13) to 2.84 +/- 0.06 V and 59.71 +/- 2.79 us (immobilized group, n=15),
      respectively. Immobilization altered the amplitude of CAP waves and decreased the
      conduction velocity of the first CAP wave (from 93.63 +/- 7.49 to 79.14 +/- 5.59
      m/s) but not of the second wave. Transmission electron microscopy showed
      fragmentation of the myelin sheath of the sciatic nerve of immobilized limbs and
      degeneration of the axon. In conclusion, we demonstrated that long-lasting leg
      immobilization can induce alterations in nerve function.

PMID- 23969979
TI  - The meddling microbes midst our medicines.
AB  - It is not surprising that the complex metabolic machinery of the gut microbiome
      has accidental, or directed, ability to alter our medicines and influence their
      efficacy. What is not known is the extent to which this has contributed to drug
      failures or contraindications, or to the derailment of clinical trials. Some
      studies are unraveling the mechanisms by which the microbiota alter specific
      drugs, such as digoxin, and contribute to variations in efficacies between
      patient populations. Microbiome profiling, therefore, may well become an
      inevitable arm of all clinical trials in the future. 

PMID- 23969980
TI  - Surgery for aortic aneurysms: how to reduce tension on the anastomosis.
AB  - We describe a simple technique we use in our institution during surgery for
      aortic aneurysms to reduce tension on the anastomosis when there is a discrepancy
      between the remnant portion of the native aorta and the vascular prosthesis. 

PMID- 23969981
TI  - Olfactory receptor 51E1 as a novel target for diagnosis in somatostatin receptor
      negative lung carcinoids.
AB  - Somatostatin receptors (SSTRs) may be used in lung carcinoids (LCs) for diagnosis
      and therapy, although additional targets are clearly warranted. This study aimed
      to investigate whether olfactory receptor 51E1 (OR51E1) may be a potential target
      for LCs. OR51E1 coding sequence was analyzed in LC cell lines, NCI-H727 and NCI
      H720. OR51E1 transcript expression was investigated in LC cell lines and frozen
      specimens by quantitative real-time PCR. OR51E1, SSTR2, SSTR3, and SSTR5
      expression was evaluated by immunohistochemistry on paraffin-embedded sections of
      73 typical carcinoids (TCs), 14 atypical carcinoids (ACs), and 11
      regional/distant metastases and compared with OctreoScan data.
      Immunohistochemistry results were rendered semiquantitatively on a scale from 0
      to 3, taking into account the cellular compartmentalization (membrane vs
      cytoplasm) and the percentage of tumor cells (<50 vs >50%). Our results showed
      that WT OR51E1 transcript was expressed in both LC cell lines. OR51E1 mRNA was
      expressed in 9 out of 12 TCs and 7 out of 9 ACs (P=NS). Immunohistochemically,
      OR51E1, SSTR2, SSTR3, and SSTR5 were detected in 85, 71, 25, and 39% of TCs and
      in 86, 79, 43, and 36% of ACs respectively. OR51E1 immunohistochemical scores
      were higher or equal than those of SSTRs' in 79% of TCs and 86% of ACs.
      Furthermore, in the LC cases where all SSTR subtypes were lacking, membrane
      OR51E1 expression was detected in 10 out of 17 TCs and 1 out of 2 ACs. Moreover,
      higher OR51E1 immunohistochemical scores were detected in 5 out of 6 OctreoScan
      negative LC lesions. Therefore, the high expression of OR51E1 in LCs makes it a
      potential novel diagnostic target in SSTR-negative tumors. 

PMID- 23969982
TI  - Lipopolysaccharide inhibits the expression of resistin in adipocytes.
AB  - Resistin is an adipocytokine leading to insulin resistance.
      Endotoxin/lipopolysaccharide (LPS) has been reported to decrease the expression
      of resistin mRNA and protein in both lean and db/db obese mice, although the
      underlying mechanism remains unclear. Several models such as ex vivo culture of
      adipose tissues, primary rat adipocytes and 3T3-L1 adipocytes were used to
      further characterize the effect of LPS on the expression of resistin. LPS
      attenuated both the resistin mRNA and protein in a time- and dose-dependent
      manner. In the presence of actinomycin D, LPS failed to reduce the half-life of
      resistin mRNA, suggesting a transcriptional mechanism. The lipid A fraction is
      crucial for the inhibition of resistin expression induced by LPS. Pharmacological
      intervention of c-Jun N-terminal kinase (JNK) reversed the inhibitory effect of
      LPS. LPS down-regulated CCAAT/enhancer-binding protein alpha (C/EBP-alpha; CEBPA)
      and peroxisome proliferator-activated receptor gamma (PPAR-gamma; PPARG), while
      activation of C/EBP-alpha or PPAR-gamma by either over-expressing these
      transcriptional factors or by rosiglitazone, an agonist of PPAR-gamma, blocked
      the inhibitory effect of LPS on resistin. C/EBP homologous protein (CHOP-10;
      DDIT3) was up-regulated by LPS, while a CHOP-10 antisense oligonucleotide
      reversed the decrement of resistin protein induced by LPS. Taken together, these
      results suggest that LPS inhibits resistin expression through a unique signaling
      pathway involving toll-like receptor 4, JNK, CHOP-10 and C/EBP-alpha/PPAR-gamma. 

PMID- 23969983
TI  - The new media of violent video games: yet same old media problems?

PMID- 23969984
TI  - Does trainee involvement affect anticipatory guidance in well-child care?
AB  - BACKGROUND: Studies demonstrate gaps in anticipatory guidance during well-child
      visits, but none consider academic teaching hospitals where physician trainees
      also provide counseling. We prospectively assessed parental perception of
      anticipatory guidance at the outpatient clinic of an academic teaching hospital.
      METHODS: Parents of patients newborn to <60 months old completed questionnaires
      regarding providers seen and anticipatory guidance preferences. RESULTS: Of 204
      parents, 40% saw the child's primary attending alone. There was no association
      between providers seen and the number of topics covered. Seeing the child's
      primary attending alone increased the odds that parents' priority topics were
      covered compared with another attending (odds ratio [OR] = 0.31; 95% confidence
      interval [CI] = 0.11-0.90) or the addition of a resident (OR = 0.35; 95% CI =
      0.16-0.77) or medical student (OR = 0.33; 95% CI = 0.12-0.90). CONCLUSIONS:
      Priority anticipatory guidance is covered only one third as often when the well
      child visit is not conducted by the primary attending. When involving trainees,
      continuity of care and parental concerns must be emphasized.

PMID- 23969985
TI  - The diagnostic yield of pediatric polysomnography based on the professional
      background of referring physicians.
AB  - INTRODUCTION: Polysomnography (PSG) is the gold standard in diagnosis of sleep
      disordered breathing but is labor intensive and expensive. We assessed PSG
      outcomes based on physician specialty and whether prior referral to sleep clinics
      reduces costs for children with sleep problems. METHODS: Retrospective analysis
      of PSGs was performed by demographics, physician specialization, PSG indication,
      and results. Average costs of evaluating PSGs ordered by primary care physicians
      (PCPs) versus initial referral to sleep specialists were compared. RESULTS: A
      total of 493 PSGs were performed between June 2010 and December 2010. Most
      referrals came from sleep physicians (31%), otolaryngologists (24%), and PCPs
      (18%). Forty-four percent PSGs ordered by PCPs were normal versus 22% by sleep
      physicians (odds ratio = 2.8, P < .05). Average cost of PSGs ordered by PCPs was
      $3053.54/patient versus $917.85/patient for sleep specialist referral.
      CONCLUSION: PSGs ordered by PCPs were more likely to be normal than PSGs by sleep
      physicians. Sleep clinic assessment before PSGs may assist in appropriate service
      utilization, improve delivery of care, and reduce health care costs by using
      these tests appropriately.

PMID- 23969986
TI  - Proteomic identification of target proteins following Drosha knockdown in
      cervical cancer.
AB  - The nuclear microRNA (miRNA) processing enzyme Drosha is upregulated in cervical
      cancer, and its overexpression is related to an invasive tumour phenotype.
      However, the mechanisms that underlie this effect remain poorly understood. The
      aim of this study was to identify the potential targets of Drosha in cervical
      cancer. Here, we demonstrated that Drosha knockdown (Drosha-KD) inhibited
      proliferation, colony formation and the migration of cervical cancer cells in
      vitro. A global upregulation of proteins in Drosha-KD cells was revealed by two
      dimensional gel electrophoresis (2-DE). Eighteen proteins were identified by
      liquid chromatography and tandem mass spectrometry technology (LC-MS/MS) from 21
      selected protein spots that exhibited significant alterations in Drosha-KD cells.
      The majority of the identified proteins have been previously associated with
      tumour formation. The downregulation of tubulin 5beta in Drosha-KD cervical
      cancer cells was further confirmed by western blotting. Our results suggest that
      Drosha affects the biological activity of cervical cancer cells by regulating the
      expression of numerous tumour-associated proteins. 

PMID- 23969988
TI  - An association study between the norepinephrine transporter gene and depression.
AB  - A potential approach for identification of candidate genes for depression is
      characterization of chromosomal rearrangements. Through analysis of a chromosome
      translocation in an individual with recurrent depression, we identified a
      potential candidate gene: the norepinephrine transporter (NET; SLC6A2 for solute
      carrier 6 family member 2). The gene is responsible for the reuptake of
      norepinephrine and dopamine into presynaptic nerve terminals and the
      norepinephrine system appears to play an important role in depression. We
      therefore analyzed genetic variants within SLC6A2 for association with depression
      in 408 affected and 559 control individuals from Denmark. After quality control
      of the genotypes, 31 of 45 single nucleotide polymorphisms (SNPs) were left for
      analyses. One SNP showed a nominal association with depression but did not
      survive correction for multiple testing. The results from our study do not
      suggest SLC6A2 as a susceptibility gene for depression in the Danish population. 

PMID- 23969989
TI  - Evidence of increased risk for major depressive disorder in individuals
      homozygous for the high-expressing 5-HTTLPR/rs25531 (L(A)) allele of the
      serotonin transporter promoter.

PMID- 23969990
TI  - Effects of stromal cell derived factor-1 and CXCR4 on the promotion of
      neovascularization by hyperbaric oxygen treatment in skin flaps.
AB  - Hyperbaric oxygen (HBO) is known to increase the survival of skin flaps by
      promoting neovascularization; however, the detailed mechanisms involved are not
      fully understood. In the present study, we aimed to characterize the effects of
      HBO treatment on neovascularization and skin flap survival. We also analyzed the
      mechanisms associated with the expression of angiogenic molecules, such as
      stromal cell derived factor-1 (SDF-1) and its specific receptor CXCR4, to assess
      the effects of SDF-1 and CXCR4 on the promotion of neovascularization by HBO
      treatment in skin flaps. The epigastric pedicle skin flap model was established
      in rats that were randomly divided into the following groups: i) sham-operated
      (SH group); ii) ischemia followed by reperfusion and analysis on the third and
      fifth day (IR3d and IR5d groups, respectively) postoperatively; iii) ischemia
      followed by reperfusion, HBO treatment and analysis on the third and fifth day
      (HBO3d and HBO5d groups, respectively) postoperatively. In the two HBO groups,
      animals received 1 h of HBO treatment in a 2.0 ATA chamber with 100% O2 twice per
      day for 3 days and then daily for 2 consecutive days following surgery. On the
      postoperative third and fifth day, skin flap survival measurement, histological
      analysis, immunohistochemical staining and western blotting for SDF-1 and CXCR4
      expression, were performed. Compared with those of the IR groups, skin flap
      survival, microvessel density (MVD) and expression of SDF-1 and CXCR4 proteins
      were significantly increased in the HBO groups. Pearson's correlation analysis
      demonstrated a positive correlation between MVD and the high expression of SDF-1
      and CXCR4 following HBO treatment. Results of this study suggested that the
      effects of HBO treatment in promoting neovascularization may be explained by the
      upregulation of SDF-1 and CXCR4 expression in the skin flaps of rats.

PMID- 23969991
TI  - Correlation of cognition and SPECT perfusion: easy Z score and SPM analysis of a
      pilot sample with cerebral small vessel disease.
AB  - BACKGROUND/AIMS: To associate neuropsychology test performance with perfusion on
      single-photon emission computed tomography (SPECT) among 12 patients with
      cerebral small vessel disease. METHODS: The easy Z score imaging system (eZIS)
      was used to compare patient images to those of normal controls. Scores from
      neuropsychological tests commonly used to screen for dementia were associated
      with SPECT resting perfusion image values using the statistical parametric
      mapping (SPM) program. RESULTS: Immediate Memory and Delayed Memory index scores,
      as well as memory subtests of the Repeatable Battery for Assessment of
      Neuropsychological Status showed cluster- and voxelwise positive correlations
      with hypoperfusion in frontal, temporal and cerebellar regions. Negative
      correlations, primarily in frontal regions, were interpreted as compensatory
      hyperperfusion. CONCLUSION: eZIS and SPM analyses of SPECT images showed
      perfusion correlations with neuropsychological tests with small vessel disease.

PMID- 23969992
TI  - Epidemiology of surgically treated primary spinal cord tumors in Miyagi, Japan.
AB  - BACKGROUND: Data for spinal cord tumors have not been collected in the past on a
      population-based level in Japan. The objective of the study was to provide
      detailed estimates of the population-based incidence of surgically treated
      primary spinal cord tumors in Japan. METHODS: Incidence of primary spinal cord
      tumors was estimated from patients treated surgically between 2008 and 2010 in
      Miyagi Prefecture. The overall incidence of spinal cord tumors was calculated, as
      well as the individual incidence rates according to age group, gender, pathology
      and tumor location. RESULTS: Of the primary spinal cord tumors identified (n =
      112), 98% were nonmalignant. The overall incidence of spinal cord tumors was
      1.60/100,000 person-years with an incidence of 1.77/100,000 in males and
      1.45/100,000 in females. The incidence rate was highest in the age group of 60-64
      years (3.04/100,000). Schwannoma accounted for 56% and meningioma accounted for
      13% of the tumors. The histological type with the highest incidence was
      schwannoma (0.90/100,000), followed by meningioma (0.20/100,000). CONCLUSIONS:
      Due to the high incidence of schwannomas, the overall incidence of spinal cord
      tumors is higher in Japan than in Western countries, and Japanese males have a
      higher incidence than females, different from that observed in Western countries.

PMID- 23969993
TI  - Increase in penguin populations during the Little Ice Age in the Ross Sea,
      Antarctica.
AB  - Penguins are an important seabird species in Antarctica and are sensitive to
      climate and environmental changes. Previous studies indicated that penguin
      populations increased when the climate became warmer and decreased when it became
      colder in the maritime Antarctic. Here we determined organic markers in a
      sediment profile collected at Cape Bird, Ross Island, high Antarctic, and
      reconstructed the history of Adelie penguin colonies at this location over the
      past 700 years. The region transformed from a seal to a penguin habitat when the
      Little Ice Age (LIA; 1500-1800 AD) began. Penguins then became the dominant
      species. Penguin populations were the highest during ca. 1490 to 1670 AD, a cold
      period, which is contrary to previous results in other regions much farther
      north. Different responses to climate change may occur at low latitudes and high
      latitudes in the Antarctic, even if for same species.

PMID- 23969994
TI  - Efficacy of musical interventions in dementia: evidence from a randomized
      controlled trial.
AB  - Although musical interventions have recently gained popularity as a non
      pharmacological treatment in dementia, there is still insufficient evidence of
      their effectiveness. To investigate this issue, a single-center randomized
      controlled trial was conducted with forty-eight patients with Alzheimer's disease
      or mixed dementia to compare the effects of music versus cooking interventions in
      the emotional, cognitive, and behavioral domain, as well as on professional
      caregiver distress. Each intervention lasted four weeks (two one-hour sessions a
      week). Multi-component evaluations (with blind assessors) were conducted before,
      during, and after the interventions to assess their short and long-term effects
      (up to four weeks post interventions). Analyses revealed that both music and
      cooking interventions led to positive changes in the patients' emotional state
      and decreased the severity of their behavioral disorders, as well as reduced
      caregiver distress. However, no benefit on the cognitive status of the patients
      was seen. While results did not demonstrate a specific benefit of music on any of
      the considered measures, the present study suggests the efficacy of two pleasant
      non-pharmacological treatments in patients with moderate to severe dementia. Our
      findings highlight the potential of such interventions in improving the well
      being of patients living in residential care, as well as reducing caregiver
      distress. 

PMID- 23969995
TI  - Memory for past public events depends on retrieval frequency but not memory age
      in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by retrograde memory deficits primarily
      caused by dysfunction of the hippocampal complex. Unresolved questions exist
      concerning the time course of hippocampal involvement in conscious recollection
      of declarative knowledge, as reports of temporal gradients of retrograde amnesia
      have been inconclusive. The aim of this study was to examine whether the extent
      and severity of retrograde amnesia is mediated by retrieval frequency or, in
      contrast, whether it depends on the age of the memory according to the
      assumptions of the main current theories of memory formation. We compared recall
      of past public events in patients with AD and healthy control (HC) individuals
      using the Historic Events Test (HET). The HET assesses knowledge about famous
      public events of the past 60 years divided into four time segments and consists
      of subjective memory rating, dating accuracy, and contextual memory tasks.
      Although memory for public events was impaired in AD patients, there was a strong
      effect of retrieval frequency across all time segments and both groups. As AD and
      HC groups derived similar benefits from greater retrieval frequency, cortical
      structures other than the hippocampal complex may mediate memory retrieval. These
      findings suggest that more frequently retrieved events and facts become more
      independent of the hippocampal complex and thus better protected against early
      damage of AD. This could explain why cognitive activity may delay the onset of
      memory decline in persons who develop AD. 

PMID- 23969996
TI  - Constructional apraxia as a distinctive cognitive and structural brain feature of
      pre-senile Alzheimer's disease.
AB  - Constructional apraxia (CA) is often, but not always, observed in patients with
      Alzheimer's disease (AD). CA is usually explained by impairment of either basic
      perceptual and motor abilities, or executive functions. This study aims to
      evaluate the structural correlates of CA in AD. Forty-eight patients with AD and
      20 healthy age-matched controls underwent a thorough neuropsychological
      investigation and an MRI scan to collect high-resolution T1-weighted data.
      Patients were classified as having (ADca) or not having (ADnonca) CA based on
      performance on the Freehand copying of drawings task. T1-weighted volumes were
      process according to the voxel based morphometry protocol, to assess the presence
      of significant differences in local to grey matter volumes in patients compared
      to controls and in ADca compared to ADnonca. Post-hoc, the mean grey matter
      volume of clusters that resulted significantly different between groups was
      regressed against the neuropsychological scores in which the two patient groups
      performed differently. A pre-senile disease onset was significantly more frequent
      in patients with CA compared to ADnonca. ADca patients also showed worse
      performances than patients with ADnonca at some tests requiring the processing of
      visuo-spatial data and testing working memory. They also showed widespread
      reductions in grey matter volume, mainly located in areas known to be implicated
      in object recognition and localization, and in maintenance and re-orienting of
      spatial attention. These findings suggest that the occurrence of CA in AD is
      often associated with a peculiar clinical onset (i.e., pre-senile),
      neuropsychological profile, and distribution of grey matter atrophy. 

PMID- 23969998
TI  - Global lung function standardisation: finally making our dream a reality?

PMID- 23970000
TI  - Au-Pd nanoalloys supported on Mg-Al mixed metal oxides as a multifunctional
      catalyst for solvent-free oxidation of benzyl alcohol.
AB  - Au-Pd nanoalloys supported on Mg-Al mixed metal oxides prepared using sol
      immobilisation are found to be highly efficient and reusable catalysts for the
      solvent-free oxidation of benzyl alcohol using molecular oxygen under low
      pressure. When using this support alloying Pd with Au resulted in an increase in
      both activity and selectivity to benzaldehyde and moreover an improved resistance
      to catalyst deactivation compared with the monometallic Pd and Au catalysts. The
      turnover number for the Au/Pd 1:1 molar ratio catalyst achieved 13,000 after 240
      min and the selectivity to benzaldehyde was maintained at 93%; this high
      catalytic activity can be retained in full after three successive uses. The
      ensemble and electronic effect of Au-Pd nanoalloys were studied by IR
      spectroscopy using CO chemisorption, XPS and HRTEM. Moreover, the bifunctional
      nature of the acid-base MgAl-MMO support was found to be important as the acid
      sites are considered to be responsible for the improvement of catalytic activity;
      while, the basic sites gave rise to high selectivity. A possible mechanism with
      Au-Pd nanoparticles as the active sites has been proposed, illustrating that the
      oxidation of benzyl alcohol can proceed through the cooperation between the Au-Pd
      nanoalloys and the base/acid sites on the surface of the support.

PMID- 23969999
TI  - Iron metabolism disturbances in the MCF-7 human breast cancer cells with acquired
      resistance to doxorubicin and cisplatin.
AB  - The development of resistance of cancer cells to therapeutic agents is the major
      obstacle in the successful treatment of breast cancer and the main cause of
      breast cancer recurrence. The results of several studies have demonstrated an
      important role of altered cellular iron metabolism in the progression of breast
      cancer and suggested that iron metabolism may be involved in the acquisition of a
      cancer cell drug-resistant phenotype. In the present study, we show that human
      MCF-7 breast cancer cells with an acquired resistance to the chemotherapeutic
      drugs doxorubicin (MCF-7/DOX) and cisplatin (MCF-7/CDDP) exhibited substantial
      alterations in the intracellular iron content and levels of iron-regulatory
      proteins involved in the cellular uptake, storage and export of iron, especially
      in profoundly increased levels of ferritin light chain (FTL) protein. The
      increased levels of FTL in breast cancer indicate that FTL may be used as a
      diagnostic and prognostic marker for breast cancer. Additionally, we demonstrate
      that targeted downregulation of FTL protein by the microRNA miR-133a increases
      sensitivity of MCF-7/DOX and MCF-7/CDDP cells to doxorubicin and cisplatin. These
      results suggest that correction of iron metabolism abnormalities may
      substantially improve the efficiency of breast cancer treatment.

PMID- 23970001
TI  - Compliance by hospitals and healthcare facilities with the revised United States
      pharmacopeia chapter 797.
AB  - All hospitals and healthcare facilities, JCAHO-accredited and non accredited,
      must comply with the revised United States Pharmacopeia Chapter 797 standards.
      For those facilites that met the January 2008 JCAHP deadline, compliance with the
      revised standards should be relatively simple to accomplish. The revised chapter
      should be read and a new gap analysis performed to determine the facility's
      compliance. Investments should be made in good training programs to make sure
      that everyone, compounding personnel and other hospital staff, is properly
      trained. The revised American Society of Health-System Pharmacists' guidelines
      for sterile compounding that will be published and available by 2010 should be
      obtained and read. This document will be a compliment to United States
      Pharmacopeia Chapter 797. Finally, the assessment tools and detailed information
      from United States Pharmacopeia Chapter 797 should be utilized to develop a good
      quality-assurance program for your hospital or healthcare facility. 

PMID- 23969997
TI  - Signaling mechanisms of glucose-induced F-actin remodeling in pancreatic islet
      beta cells.
AB  - The maintenance of whole-body glucose homeostasis is critical for survival, and
      is controlled by the coordination of multiple organs and endocrine systems.
      Pancreatic islet beta cells secrete insulin in response to nutrient stimuli, and
      insulin then travels through the circulation promoting glucose uptake into
      insulin-responsive tissues such as liver, skeletal muscle and adipose. Many of
      the genes identified in human genome-wide association studies of diabetic
      individuals are directly associated with beta cell survival and function, giving
      credence to the idea that beta-cell dysfunction is central to the development of
      type 2 diabetes. As such, investigations into the mechanisms by which beta cells
      sense glucose and secrete insulin in a regulated manner are a major focus of
      current diabetes research. In particular, recent discoveries of the detailed role
      and requirements for reorganization/remodeling of filamentous actin (F-actin) in
      the regulation of insulin release from the beta cell have appeared at the
      forefront of islet function research, having lapsed in prior years due to
      technical limitations. Recent advances in live-cell imaging and specialized
      reagents have revealed localized F-actin remodeling to be a requisite for the
      normal biphasic pattern of nutrient-stimulated insulin secretion. This review
      will provide an historical look at the emergent focus on the role of the actin
      cytoskeleton and its regulation of insulin secretion, leading up to the cutting
      edge research in progress in the field today. 

PMID- 23970002
TI  - Tips for cleanroom construction and renovation.
AB  - The installation or renovation of a cleanroom is an increasing priority among
      compounders who, to offer sterile preparations, must comply with the most recent
      version of United States Pharmacopeia revised General Chapter 797 guidelines. To
      upgrade their pharmacy facilites, many compounders have worked successfully with
      a large-scale mechanical engineering firm or a specialized construction company
      dedicated to cleanroom installation. However, a qualified local mechanical
      contractor with design capability is a valuable and often overlooked resource for
      the construction of customized stae-of-the-art cleanrooms. In this report, we
      describe the installation of such a facility in a busy pharmacy and suggest ways
      in which compounding pharmacists can identify competent local contractors and
      control the cost of construction and upgrades. The addition of a cleanroom has
      enabled The Compounding Pharmacy in Hickory, North Carolina, to achieve
      accreditation from the Pharmacy Compounding Accreditation Board. 

PMID- 23970003
TI  - Contract sterilization and validation companies offer new options for sterile
      compounded preparations.
AB  - To ensure patient safety, adhere to good compounding practices, and safeguard
      against professional liability, the sterility of some compounded preparations
      must be assured. When in-house sterilization capabilities do not suffice, the
      intervention of a contract sterilization and/or validation company can assist in
      establishing the sterility, purity, and potency of the pharmaceuticals used in
      compounded preparations. In this article, three contract steriliziation companies
      and two contract validation firms are profiled, methods that compounders can use
      to best interface with those companies are presented, and sterilization and
      validation processes are explained and compared. 

PMID- 23970004
TI  - Treating methicillin-resistant Staphylococcus aureus infections with compounded
      vancomycin preparations.
AB  - Methicillin-Resistant Staphylococcus aureus infections have been an ongoing
      problem with institutions. Unfortunately, the problem has crossed over into the
      community setting. Drug resistance develops so rapidly that it is difficult for
      drug manufacturers to develop new treatment options in a timely manner.
      Compounding pharmacists can help physicians treat their Methicillin-Resistant
      Staphylococcus aureus patients by assisting them in developing new dosage forms
      or therapies to treat these difficult infections and providing patient counseling
      to prevent infection. 

PMID- 23970005
TI  - Compendial activities relating to cold chain management issues: drug products and
      compounded preparations.
AB  - The expansion of distibution pathways by emerging technologies has heightened the
      expectations of those involved in the area of drug storage and transportation.
      Medicines are now transported to remote areas of the world. Some of these
      medicines include HIV medications that may require refrigeration or special
      handling. Added to this, advances in healthcare treatment have allowed the use of
      complex biologics and proteins, as well as specialized compounded preparations
      such as biiodegradable hormone therapy that require special handling and specific
      storage methods. Because of these factors, the temperature and humidity to which
      these complex active medicines are exposed need to be critically studied and
      evluated because damage to these medicines could become irriversible and
      expensive. This article discusses the past and present activities of United
      States Pharmacopeia in the area of cold chain management with emphasis on
      appropriate methods of handling, storing, and shipping of these medicines. 

PMID- 23970006
TI  - Incorporating web communication to maximize staff productivity in a compounding
      pharmacy.
AB  - Regular, task-oriented staff meetings will have a positive impact in your
      phamracy practice and will improve your management style. The three major
      objectives discussed in this article are to convince pharmacists to conduct
      regular staff meetings; introduce a tried-and-true, mission-critical agenda for
      each meeting; and introduce pharmacists to an Internet-based technology resource
      for creating a task-centered, practice management approach with the pharmacy
      staff. Another great advantage for using the approach described here is that
      you'll have everything documented for each staff member's impact on your pharmacy
      practice during their end-of-year review. 

PMID- 23970007
TI  - Quality-control analytical methods: compounding slow-release pharmaceuticals.
AB  - Slow-release dosage forms are designed to release active drugs at slower rates
      for prolonging drug effects. These unconventional dosage forms are complex drug
      delivery systems, which require specialized technical knowledge and skills in
      their formulation. Verification of the compounding process for slow-release oral
      dosage forms can be accomplished through quality-control testing of pilot batches
      to ensure acceptable preparation and patient safety. 

PMID- 23970008
TI  - Basics of compounding: considerations for implementing United States pharmacopeia
      chapter 797 pharmaceutical compounding-sterile preparations, part 12.
AB  - It is crucial that proper methods be employed to successfully adhere to the
      requirements, practices, and procedures critical to maintaining sterility,
      accuracy, and purity of a finished compounded sterile preparation. Various
      methods of sterilization can be used, depending upon a solution's
      characteristics. Although other methods can be used, the three primary methods of
      sterilization for compounding pharmacists are: (1)filtration, (2)moist heat, and
      (3)dry heat, all of which are discussed in this article. Each method requires
      equipment choices (e.g., filters, autoclave, dry oven), and this article briefly
      discusses some of the criteria that should be considered when selecting the
      proper equipment for the selected method. 

PMID- 23970009
TI  - Drug Compatibility with a New Generation of VISIV Polyolefin Infusion Solution
      Containers.
AB  - A new generation of VISIV polyolefin intravenous solution containers, made of a
      new and different proprietary polymer, were evaluated for sorption and leaching
      potential with a cadre of drugs known to exhibit those phenomena with
      polyvinylchloride containers. Sorption potential was evaluated for amiodarone
      hydrochloride, carmustine, regular human insulin, lorazepam, nitroglycerin,
      sufentanil citrate, and thiopental sodium. Leaching potential was evaluated for
      tacrolimus and teniposide as well as the vehicles of docetaxel and paclitaxel.
      Representative concentrations of the drugs in infusion solutions or undiluted
      were placed into the new generation of VISIV containers and left in contact for
      up to 24 hours at room temperature. High performance liquid chromatography was
      used to determine drug concentrations and the presence of plasticizer or other
      plastic components, if any. Only regular human insulin exhibited any substantial
      loss of concentration in the polyolefin containers that could be attirbuted to
      sorption. Other drugs' concentrations were consistent with their stabilities over
      the test periods. No evidence of leaching of plasiticizer or other plastic
      components was observed. 

PMID- 23970010
TI  - Stability of low-concentration ceftazidime in 0.9% sodium chloride injection and
      balanced salt solutions in plastic syringes under various storage conditions.
AB  - The objective of this study was to assess the stability of ceftazidime in 0.9%
      sodium chloride injection and balanced salt solutions. Ceftazidime was dissolved
      in 0.9% sodium chloride injection or balanced salt solution at a concentration of
      1 mg/mL. Samples of these solutions were then stored under three different sets
      of conditions, ambient temperature (25 deg C), refrigeration (4 deg C), or frozen
      (-20 deg C). The concentration of ceftazidime in each solution was determined at
      various intervals using the high-performnace liquid chromatographic method
      outlined in the United States Pharmacopeia-National Formulary. Our results show
      that ceftazidime was stable (>90% concentration) for up to 72 hours in both 0.9%
      sodium chloride injection and balanced salt solutions at ambient temperature.
      Ceftazidime was stable in both solutions in the refrigerator for 17 days. No
      siginificant degradation was noticed for up to 60 days when the solutions were
      kept in the freezer. 

PMID- 23970011
TI  - Stability of melatonin in an extemporaneously compounded sublingual solution and
      hard gelatin capsule.
AB  - This study examined the stability of melatonin in a 10-mg/mL oral sublingual
      solution stored at 4 deg C or 25 deg C and in 3-mg capsules stored at ambient (25
      deg C; 60% relative humidity) and accelerated (40 deg C; 75% relative humidity)
      conditions over a period of 90 days. A sublingual solution of melatonin 10 mg/mL
      was preprared with glycerin, ethyl alcohol, stevia powder extract, and tutti
      frutti flavor. Six identical solutions were prepared and stored in prescription
      amber glass bottles at 4 deg C or 25 deg C. Triplicate 1-mL samples from each of
      the six solutions were assayed immediately after preparation and after 7, 14, 28,
      60, and 90 days with a stability-indicating high-performance liquid
      chromatographic method. Six batches of 100 melatonin 3-mg capsules were prepared
      with Methocel E4M and lactose anhydrous and stored in prescription amber glass
      bottles at ambient or accelerated conditions. A sample of 10 capsules from each
      batch was assayed immediately after preparation, and additional examples from
      each storage condition were assayed at 7, 14, 28, 60, and 90 days. The mean
      concentration of melatonin exceeded 98% of the initial concentration throughout
      th 90-day study period for the sublingual solution and capsules under all storage
      conditions. There were no detectable changes in color, odor, taste, or pH, and no
      visible microbial growth in any of the sublingual solution samples. Compendia
      requirements for content uniformity were met for the extemporaneously prepared
      capsules. Melatonin in an extemporaneously compounded sublingual solution (10
      mg/mL) was stable for at least 90 days when stored in prescription amber glass
      bottles at 4 deg C or 25 deg C. Melatonin in extemporaneously prepared capsules
      (3 mg) was stable for at leaast 90 days when stored in prescription amber glass
      bottles at ambient or acclereated conditions. 

PMID- 23970012
TI  - Anaemia in pregnancy--not just iron deficiency.

PMID- 23970013
TI  - PINCH expression in relation to radiation response in co-cultured colon cancer
      cells and in rectal cancer patients.
AB  - Particularly interesting new cysteine-histidine rich protein (PINCH), involved in
      cell spreading, motility and proliferation, has been shown to enhance
      radioresistance in colon cancer cell lines. The expression of PINCH in relation
      to radiation was studied in co-cultured colon cancer cells. Furthermore, the
      clinical significance between PINCH and radiotherapy (RT) was analyzed in rectal
      cancer patients with or without RT. The relative PINCH expression in colon cancer
      (KM12C) cells cultured separately and in co-culture was examined by western
      blotting and real-time PCR, and was analyzed over a period of 8 and 24 h after
      radiation. PINCH expression was immunohistochemically examined in 137 primary
      rectal tumors for which 65 cases did not receive RT and 72 cases received RT.
      PINCH expression tended to decrease from that in the separately cultured KM12C
      cells without radiation to that in cells with radiation at 8 h (P=0.060); while
      in the co-cultured cells, no significant difference was found (P=0.446). In
      patients with RT, strong PINCH expression was related to worse survival, when
      compared to patients with weak expression, independent of TNM stage, degree of
      differentiation, age and p53 status (P=0.029, RR 4.03, 95% CI 1.34-12.1). No
      survival relationship for the patients without RT was observed (P=0.287). A
      statistical interaction analysis between PINCH, RT and survival showed a trend
      towards significance (P=0.057). In conclusion, PINCH predicts survival in rectal
      cancer patients with RT, but not in patients without RT. The expression of PINCH
      may be regulated by radiation and by environmental factors surrounding the cells.

PMID- 23970014
TI  - A Bayesian network meta-analysis for binary outcome: how to do it.
AB  - This study presents an overview of conceptual and practical issues of a network
      meta-analysis (NMA), particularly focusing on its application to randomised
      controlled trials with a binary outcome of interest. We start from general
      considerations on NMA to specifically appraise how to collect study data,
      structure the analytical network and specify the requirements for different
      models and parameter interpretations, with the ultimate goal of providing
      physicians and clinician-investigators a practical tool to understand pros and
      cons of NMA. Specifically, we outline the key steps, from the literature search
      to sensitivity analysis, necessary to perform a valid NMA of binomial data,
      exploiting Markov Chain Monte Carlo approaches. We also apply this analytical
      approach to a case study on the beneficial effects of volatile agents compared to
      total intravenous anaesthetics for surgery to further clarify the statistical
      details of the models, diagnostics and computations. Finally, datasets and models
      for the freeware WinBUGS package are presented for the anaesthetic agent example.

PMID- 23970015
TI  - Ki67 levels as predictive and prognostic parameters in pretherapeutic breast
      cancer core biopsies: a translational investigation in the neoadjuvant GeparTrio
      trial.
AB  - BACKGROUND: The proliferation marker Ki67 has been suggested as a promising
      cancer biomarker. As Ki67 needs an exact quantification, this marker is a
      prototype of a new generation of tissue-based biomarkers. In this study, we have
      systematically evaluated different cut points for Ki67 using three different
      clinical end points in a large neoadjuvant study cohort. PATIENTS AND METHODS: We
      have evaluated pretherapeutic Ki67 levels by immunohistochemistry in 1166 breast
      cancer core biopsies from the neoadjuvant GeparTrio trial. We used the
      standardized cutoff-finder algorithm for three end points [response to
      neoadjuvant chemotherapy (pCR), disease-free (DFS) and overall-survival (OS)].
      The analyses were stratified for hormone receptor (HR) and HER2 status by
      molecular subtype radar diagrams (MSRDs). RESULTS: A wide range of Ki67 cut
      points between 3%-94% (for pCR), 6%-46% (for DFS) and 4%-58% (for OS) were
      significant. The three groups of Ki67 <= 15% versus 15.1%-35% versus >35% had pCR
      rates of 4.2%, 12.8%, and 29.0% (P < 0.0005), this effect was also present in six
      of eight molecular subtypes. In MSRD, Ki67 was significantly linked to prognosis
      in uni- and multivariate analysis in the complete cohort and in HR-positive, but
      not triple-negative tumors. CONCLUSIONS: Ki67 is a significant predictive and
      prognostic marker over a wide range of cut points suggesting that data-derived
      cut point optimization might not be possible. Ki67 could be used as a continuous
      marker; in addition, the scientific community could define standardized cut
      points for Ki67. Our analysis explains the variability observed for Ki67 cut
      points in previous studies; however, this should not be seen as weakness, but as
      strength of this marker. MSRDs are an easy new approach for visualization of
      biomarker effects on outcome across molecular subtypes in breast cancer. The
      experience with Ki67 could provide important information regarding the
      development and implementation of other quantitative biomarkers.

PMID- 23970016
TI  - Ulcer, gastric surgery and pancreatic cancer risk: an analysis from the
      International Pancreatic Cancer Case-Control Consortium (PanC4).
AB  - BACKGROUND: Peptic ulcer and its treatments have been associated to pancreatic
      cancer risk, although the evidence is inconsistent. METHODS: We pooled 10 case
      control studies within the Pancreatic Cancer Case-control Consortium (PanC4),
      including 4717 pancreatic cancer cases and 9374 controls, and estimated summary
      odds ratios (OR) using multivariable logistic regression models. RESULTS: The OR
      for pancreatic cancer was 1.10 [95% confidence interval (CI) 0.98-1.23] for
      history of ulcer (OR = 1.08 for gastric and 0.97 for duodenal ulcer). The
      association was stronger for a diagnosis within 2 years before cancer diagnosis
      (OR = 2.43 for peptic, 1.75 for gastric, and 1.98 for duodenal ulcer). The OR was
      1.53 (95% CI 1.15-2.03) for history of gastrectomy; however, the excess risk was
      limited to a gastrectomy within 2 years before cancer diagnosis (OR = 6.18, 95%
      CI 1.82-20.96), while no significant increased risk was observed for longer time
      since gastrectomy. No associations were observed for pharmacological treatments
      for ulcer, such as antacids, H2-receptor antagonists, or proton-pump inhibitors.
      CONCLUSIONS: This uniquely large collaborative study does not support the
      hypothesis that peptic ulcer and its treatment materially affect pancreatic
      cancer risk. The increased risk for short-term history of ulcer and gastrectomy
      suggests that any such association is due to increased cancer surveillance.

PMID- 23970017
TI  - Lymphoma occurring in patients over 90 years of age: characteristics, outcomes,
      and prognostic factors. A retrospective analysis of 234 cases from the LYSA.
AB  - BACKGROUND: Lymphoma occurring in patients aged 90 or older is not uncommon, and
      its incidence is expected to increase over time. Management of these patients is
      difficult given their underlying fragility and the lack of information regarding
      this population. PATIENTS AND METHODS: We retrospectively analyzed 234 patients
      diagnosed with lymphoma at the age of 90 years or older (90+) between 1990 and
      2012 to describe their characteristics, management, outcomes and prognostic
      factors. RESULTS: The median age was 92 years; 88% were B-cell lymphomas
      consisting mainly in diffuse large B-cell lymphoma. The median overall survival
      (OS) was 7.2 months (range, 0-92 months) for the 227 patients with non-Hodgkin
      Lymphoma (NHL), with a significant difference between aggressive and indolent NHL
      (5.2 months versus 19.4 months, respectively). We further analyzed 166 NHL
      patients for whom detailed characteristics were available. Among these patients,
      63.5% received a treatment, either local (7.5%) or systemic (56%). Lymphoma was
      reported as the main cause of death (40%). Treatment administration was
      associated with improved OS in patients with aggressive (P < 0.001) but not
      indolent NHL (P = 0.96). In patients with aggressive NHL, hypoalbuminemia
      appeared as a strong and independent negative prognostic factor. CONCLUSIONS: The
      median OS is short in 90+ patients diagnosed with lymphoma but some patients
      experience prolonged survival. Lymphoma represents the main cause of death in
      these patients. Treatment may improve survival of selected patients with
      aggressive but not indolent NHL. Management of these patients may be guided by
      prognostic factors identified in this study, notably serum albumin.

PMID- 23970018
TI  - Acute myeloblastic leukaemias in adult patients: ESMO Clinical Practice
      Guidelines for diagnosis, treatment and follow-up.

PMID- 23970019
TI  - Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment
      and follow-up.

PMID- 23970020
TI  - Constipation in patients with thiamine deficiency after Roux-en-Y gastric bypass
      surgery.
AB  - BACKGROUND/AIMS: Roux-en-Y gastric bypass surgery is the most common bariatric
      surgery worldwide. We have described thiamine deficiency in patients with small
      intestinal bacterial overgrowth after gastric bypass. We hypothesized that
      symptoms of thiamine deficiency are common after gastric bypass. The aims of this
      study were to examine the prevalence of and treatment of symptoms of thiamine
      deficiency after gastric bypass. METHODS: This is a prospective study performed
      in a large urban, community hospital. Consecutive gastric bypass patients seen
      from February 1, 2008 to May 1, 2009 are included. Thiamine deficiency in this
      study included both: consistent clinical symptoms and either (1) low blood
      thiamine level or (2) resolution of clinical symptoms after receiving thiamine.
      RESULTS: Of 151 patients, 25 females and 2 males met the criteria for thiamine
      deficiency (prevalence of 18%). In these 27 patients, 12 had one symptom of
      thiamine deficiency, while 15 had symptoms consistent with multiple subtypes.
      Eleven patients reported constipation at 0.33-12 years (mean 4.8) after gastric
      bypass. Elevated serum folate levels were seen in 6 of 10 tested patients and
      there was an abnormal glucose-hydrogen breath test in 9 of 10 tested patients,
      supporting the presence of small intestinal bacterial overgrowth. Frequency of
      defecation improved after thiamine treatment. CONCLUSION: Thiamine deficiency
      resulting from small intestinal bacterial overgrowth should be considered in
      patients being seen for constipation after gastric bypass surgery.

PMID- 23970021
TI  - Tuning the band gap of mesoporous Zr-doped TiO2 for effective degradation of
      pesticide quinalphos.
AB  - This paper has focused on the synthesis and modification of TiO2 nanomaterial via
      an acid modified sol-gel process. ZrOCl2 was used as a source of Zr for doping
      titania. The nanomaterials were characterized by electron microscopy, X-ray
      diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared
      spectroscopy, N2 adsorption-desorption isotherms, UV-visible diffuse reflectance
      spectroscopy, etc. Changes in the band gap of the synthesized nanomaterials were
      studied with respect to the dopant amount, and the performance of the synthesized
      nanomaterials was evaluated as a photocatalyst to degrade pesticide quinalphos in
      aqueous solution under UV light. Anatase TiO2 nanocrystallites with an average
      size of ca. 8-11 nm were obtained depending on the amount of dopant. The results
      showed that the amount of dopant significantly altered the band gap as well as
      the surface properties of the hybrid nanomaterials which resulted in high
      photocatalytic activity. 

PMID- 23970022
TI  - NMR study of the supramolecular structure of dual drug-loaded
      poly(butylcyanoacrylate) nanoparticles.
AB  - Nuclear magnetic resonance (NMR) spectroscopy has been used for structural
      characterization of 5-fluorouracil (5FU) & daunorubicin (DAU) co-loaded
      poly(butylcyanoacrylate) nanoparticles (PBCN), prepared by an anionic
      polymerization of n-butylcyanoacrylate, probing two different drug loading
      approaches. Diffusion ordered spectroscopy, obtained through pulsed field
      gradient NMR experiments, has been performed to determine the overall structure
      of the 5FU & DAU co-loaded PBCN and to clarify the mechanisms of drug
      immobilization and location in the polymer matrix of PBCN. Physicochemical
      properties such as composition, size, surface chemistry and shape have been
      defined. All data obtained have been referred to the dual drug-loading procedures
      employed. The results show that 5FU & DAU co-loaded PBCN can be designed to
      exhibit different properties, composition and overall structure, depending on the
      method of preparation. The structural attributes relate to the drug efficacy and
      reactivity characteristics such as capacity for sustained drug release, targeted
      drug delivery, drug penetration, retention in and transport through bio
      membranes. The design of nanoparticle platforms to deliver multiple drugs for
      combination therapy offers the opportunity for novel strategies in an effort to
      increase the efficacy of cancer therapy. 

PMID- 23970023
TI  - Long-term outcome of intravitreal ranibizumab treatment, compared with
      photodynamic therapy, in patients with polypoidal choroidal vasculopathy.
AB  - PURPOSE: To evaluate the functional outcomes of patients with polypoidal
      choroidal vasculopathy (PCV) who underwent intravitreal ranibizumab (IVR)
      treatment, compared with photodynamic therapy (PDT), after at least 2 years.
      METHODS: We retrospectively studied all the treatment-naive patients with PCV who
      were scheduled to undergo IVR or PDT between August 2005 and June 2010. All the
      patients who had a 2-year or longer follow-up period were included in the study.
      The best-corrected visual acuity (BCVA) in the two groups was compared before
      treatment and at 3, 6, 12, 18 and 24 months after the initial treatment. The
      regression of the polyps was also assessed using indocyanine green angiography.
      RESULTS: A total of 77 patients were included in this study. Thirty-three eyes
      were treated with IVR, and 44 eyes were treated with PDT. Although no significant
      differences between the two groups were observed at baseline or at 3, 6, and 12
      months after treatment, a significantly better BCVA was seen in the IVR group,
      compared with the PDT group, at 18 and 24 months after treatment (P=0.035 and
      P=0.021, respectively). No significant difference in the rate of polyp regression
      was observed between the two groups (P=0.092). CONCLUSION: IVR was well tolerated
      and maintained or improved the vision of patients with PCV, compared with PDT, as
      evaluated at 2-year follow-up examinations. PDT for the treatment of PCV might
      result in unfavorable outcomes, with no superiority to achieving the involution
      of polyps.

PMID- 23970024
TI  - Eye drop instillation technique in patients with glaucoma.
AB  - AIMS: To evaluate the technique of eye drop instillation in patients with
      glaucoma and assess factors associated with a good technique. METHODS: A cross
      sectional observational study of 85 participants using self-administered topical
      medication for glaucoma or ocular hypertension. Patients were asked to
      demonstrate how they normally instil eye drops using a 5-ml bottle of sterile
      artificial tear solution. The procedure was recorded and assessed by two masked
      graders. Whether the patient had been previously shown how to instil drops, the
      number of eye medications used, and self-perceived difficulty of using drops were
      also recorded. Univariable logistic regression was performed to relate each
      variable to drop technique and variables with P<0.2 were included in a
      multivariable logistic regression analysis. RESULTS: 54.1% (46/85) of patients
      had a poor drop technique, 11.8% (10/85) missed the eye, 15.3% (13/85) touched
      the tip of the bottle to the bulbar conjunctiva or cornea, and 27.1% (23/85)
      touched the eyelid or lashes with the bottle tip. 81.2% (69/85) could not recall
      being shown how to instil eye drops. In the multivariable model, previous
      instruction regarding drop instillation technique was significantly associated
      with good technique (adjusted OR=8.17, 95% CI 2.02-33.05, P=0.003) and increasing
      age was associated with poor technique (adjusted OR=0.95, 95% CI 0.91-0.99,
      P=0.017). CONCLUSIONS: Education relating to eye drop instillation technique is
      significantly associated with a patient's ability to instil drops correctly. The
      assessment of a patient's ability to instil eye drops correctly should be a
      routine part of the glaucoma examination.

PMID- 23970025
TI  - Pseudoexfoliation syndrome and cardiovascular disease: studies must control for
      all cardiovascular risk factors.

PMID- 23970026
TI  - Reply: Pseudoexfoliation syndrome and cardiovascular disease: studies must
      control for all cardiovascular risk factors.

PMID- 23970027
TI  - The development of a virtual reality training programme for ophthalmology:
      repeatability and reproducibility (part of the International Forum for Ophthalmic
      Simulation Studies).
AB  - PURPOSE: To evaluate the variability of performance among novice ophthalmic
      trainees in a range of repeated tasks using the Eyesi virtual reality (VR)
      simulator. METHODS: Eighteen subjects undertook three attempts of five cataract
      specific and generic three-dimensional tasks: continuous curvilinear
      capsulorhexis, cracking and chopping, cataract navigation, bimanual cataract
      training, anti-tremor. Scores for each attempt were out of a maximum of 100
      points. A non-parametric test was used to analyse the data, where a P-value of
      <0.05 was considered statistically significant. RESULTS: Highly significant
      differences were found between the scores achieved in the first attempt and that
      during the second (P<0.0001) and third (P<0.0001) but not between the second and
      third attempt (P=0.65). There was no significant variability in the overall score
      between the users (P=0.1104) or in the difference between their highest and
      lowest score (P=0.3878). Highly significant differences between tasks were shown
      both in the overall score (P=0.0001) and in the difference between highest and
      lowest score (P=0.003). CONCLUSION: This study, which is the first to quantify
      reproducibility of performance in entry level trainees using a VR tool,
      demonstrated significant intra-novice variability. The cohort of subjects
      performed equally overall in the range of tasks (no inter-novice variability) but
      each showed that performance varies significantly with the complexity of the task
      when using this high-fidelity instrument.

PMID- 23970028
TI  - Two-step retrograde closed stenting: a novel method for treating canalicular
      lacerations in Chinese patients.
AB  - PURPOSE: To evaluate the efficacy of two-step retrograde closed stenting for
      treating canalicular laceration. methods: Forty-eight consecutive canalicular
      laceration cases (48 eyes) were randomised and divided into two groups: a one
      step group and a two-step group. In the two-step group (23 cases), the first step
      was performed in the outpatient department and included identifying the medial
      cut end of the canaliculus and probing under a slit-lamp microscope, followed by
      a retrograde canalicular stenting assisted by a memory titanium stylet. The
      second step was canalicular anastomosis, which was performed in the operating
      room. In the one-step group (25 cases), all of the surgical procedures were
      performed when preoperative preparations were simultaneously available. RESULTS:
      The time elapsed from the doctor visit to the treatment was 4.3 +/- 2.4 h in the
      two-step group and 18.8 +/- 6.3 h in the one-step group (P<0.01). The canalicular
      medial cut ends were found in all cases, but 8.6 +/- 3.5 min was needed in the
      two-step group, and 51.4 +/- 24.2 min was needed in the one-step group (P<0.01).
      The numerical rating scale for pain during surgery was 1.8 +/- 1.2 in the two
      step group and 5.4 +/- 2.2 in the one-step group (P<0.01). One case (2.63%) in
      the two-step group and nine cases (36%) in the one-step group required other
      assisted methods to locate the medial cut end (P=0.007). Twenty-one cases (91.3%)
      in the two-step group and 20 cases (80%) in the one-step group achieved patent
      lacrimal drainage systems during a 12-month follow-up (P=0.528). CONCLUSIONS: The
      two-step canalicular anastomosis method allows an early search for the medial cut
      end of the canaliculus and improves the chances of finding it; it is also a
      quicker, less invasive method for treating canalicular lacerations.

PMID- 23970029
TI  - Functional changes after treatment of optic pathway paediatric low-grade gliomas.
AB  - OBJECTIVE: To evaluate the functional changes after treatment of paediatric optic
      pathway gliomas (OPGs). METHODS: All patients with monofocal OPG seen from
      January 2004 to January 2011 were included. Best corrected visual acuity (BCVA,
      LogMAR), contrast sensitivity (Hiding-Heidi low-contrast 'face' test (HH) and
      Pelli-Robson (PR) contrast sensitivity test), and the Color Test (Ishihara plate)
      were obtained. RESULTS: Twenty-one patients (10 boys and 11 girls with a mean age
      of 5.5 +/- 4.4 years at diagnosis) were included in the study. Neurofibromatosis
      was present in four cases. Eighteen patients (85.7%) were treated with initial
      surgery and three patients (14.3%) with initial chemotherapy. BCVA was 0.67 +/-
      0.8 LogMAR at baseline and 0.62 +/- 0.9 LogMAR at last visit (P=0.41). The Color
      test was not significantly changed at last visit (P=0.62). Contrast sensitivity
      with the HH test was 9.1 +/- 11.1% at baseline and 3.8 +/- 6.4% at last visit
      (P=0.03). Contrast sensitivity with PR chart was 1.33 +/- 0.9 log at baseline and
      1.05 +/- 0.7 log at last visit (P=0.005). A reduction in contrast sensitivity at
      both tests was significantly greater in patients who relapsed than in patients
      who did not relapse (P=0.001). CONCLUSION: After the treatment of paediatric
      optic pathway low-grade gliomas, a reduction in contrast sensitivity during
      follow-up was observed and may be correlated with tumour relapses.

PMID- 23970030
TI  - Cognitive function, drusen, and age-related macular degeneration: a cross
      sectional study.
AB  - PURPOSE: To examine the cross-sectional relationship between drusen, late age
      related macular degeneration (AMD), and cognitive function. METHODS; We included
      2149 stroke-free participants from the population-based Tromso Study in Norway.
      Retinal photographs were graded for presence of drusen and AMD. Cognitive
      function was assessed using the verbal memory test (short verbal memory), digit
      symbol coding test (processing speed), and the tapping test (psychomotor tempo).
      We assessed the relationship between drusen, late AMD, and cognitive test scores,
      adjusted for potential confounders. RESULTS: Late AMD was associated with
      decreased performance in the verbal memory test (standardized beta=-0.23, 95%
      confidence interval (CI): -0.51 to -0.01). Intermediate and large drusen were
      associated with decreased performance in the digit-symbol coding test
      (standardized beta=-0.14 and -0.19, 95% CIs: -0.23 to -0.05 and -0.29 to -0.09,
      respectively). Participants with large drusen were more likely to have test
      scores in the lowest quartile of the digit-symbol coding test (odds ratio
      (OR)=1.9, 95% CI: 1.1-3.5) and the tapping test (OR=1.6, 95% CI: 1.0-2.6), but
      not in the verbal memory test (OR=1.0, 95% CI: 0.6-1.6). CONCLUSIONS: The
      findings suggest a relationship between drusen deposition and reduced cognitive
      function. Although the relationships between drusen, late AMD, and the cognitive
      test results varied in strength and significance across the types of cognitive
      test, and may partly have been caused by residual confounding, it is not unlikely
      that a genuine but weaker relationship exists between drusen deposition and
      cognitive decline.

PMID- 23970031
TI  - Progression of retinal changes in Gaucher disease: a case report.

PMID- 23970033
TI  - Immobilizing CdS quantum dots and dendritic Pt nanocrystals on thiolated graphene
      nanosheets toward highly efficient photocatalytic H2 evolution.
AB  - We report the development of a highly efficient photocatalytic system by
      immobilizing high-quality CdS quantum dots and dendritic Pt nanocrystals on thiol
      functionalized graphene substrates. We have demonstrated that the use of QDs with
      compact sizes leads to a dramatically enhanced performance in comparison with
      their bulk counterparts. Our design allows for systematic examination of the
      impact of QD sizes and the loading, morphology, and surface coating of the Pt
      nanocrystal cocatalyst on the H2 evolution activity. It was found that the CdS-Pt
      binary system has a high photocatalytic efficiency of 1.37 mmol h(-1) for visible
      light driven H2 evolution, and there was a 30% improvement by introducing the
      thiolated reduced graphene oxide to form the three-component CdS-Pt-Gcys
      nanocomposites. The highest H2 evolution rate of 2.15 mmol h(-1) (lambda >= 420
      nm) with a QE of 50.7% was achieved by further photo-annealing of the CdS-Pt-Gcys
      nanocomposites prior to the photocatalytic reaction. 

PMID- 23970032
TI  - Oncogenic function of p34SEI-1 via NEDD4-1-mediated PTEN
      ubiquitination/degradation and activation of the PI3K/AKT pathway.
AB  - A 34-KD protein encoded by the SEI-1 gene (p34(SEI-1)), is a relatively recently
      discovered oncoprotein that has multiple important biological functions. Our data
      show that p34(SEI-1) enhances cancer cell survival and promotes tumorigenesis by
      downregulating the tumor suppressor PTEN, a negative regulator of the PI3K/AKT
      signaling pathway, and therefore activating the PI3K/AKT signaling pathway. In
      this process, p34(SEI-1) positively affects NEDD4-1 gene expression both at the
      transcriptional and protein levels. Furthermore, the expression levels of p34(SEI
      1) and NEDD4-1 were found to be coordinated in tumor tissues obtained from
      patients with breast cancer. We also show that p34(SEI-1) affects the subcellular
      localization of PTEN.

PMID- 23970034
TI  - Photon emission from melanoma cells during brief stimulation by patterned
      magnetic fields: is the source coupled to rotational diffusion within the
      membrane?
AB  - If parameters for lateral diffusion of lipids within membranes are macroscopic
      metaphors of the angular magnetic moment of the Bohr magneton then the energy
      emission should be within the visible wavelength for applied ~1 uT magnetic
      fields. Single or paired digital photomultiplier tubes (PMTs) were placed near
      dishes of ~1 million B16 mouse melanoma cells that had been removed from
      incubation. In very dark conditions (10(-11) W/m(2)) different averaged (RMS)
      intensities between 5 nT and 3.5 uT were applied randomly in 4 min increments.
      Numbers of photons were recorded directly over or beside the cell dishes by PMTs
      placed in pairs within various planes. Spectral analyses were completed for
      photon power density. The peak photon emissions occurred around 1 uT as predicted
      by the equation. Spectra analyses showed reliable discrete peaks between 0.9 and
      1.8 uT but not for lesser or greater intensities; these peak frequencies
      corresponded to the energy difference of the orbital-spin magnetic moment of the
      electron within the applied range of magnetic field intensities and the standard
      solution for Rydberg atoms. Numbers of photons from cooling cells can be modified
      by applying specific intensities of temporally patterned magnetic fields. There
      may be a type of "cellular" magnetic moment that, when stimulated by intensity
      tuned magnetic fields, results in photon emissions whose peak frequencies reflect
      predicted energies for fundamental orbital/spin properties of the electron and
      atomic aggregates with large principal quantum numbers. 

PMID- 23970035
TI  - Suppression of exaggerated neuronal oscillations by oxytocin in a rat model of
      Parkinson's disease.
AB  - Increased oscillatory activity has been demonstrated in the basal ganglia of
      Parkinson's disease (PD) patients. The aim of the present study was to evaluate
      the effects of oxytocin on local field potentials (LFPs) in a rotenone-induced
      rat model of PD. Adult male Sprague-Dawley rats were unilaterally injected with
      rotenone (3 ug/ul in DMSO) into the left substantia nigra pars compacta whereas
      vehicle group was received only DMSO. PD developed rats were then administered
      either oxytocin (160 ug/kg/day, i.p.) or saline for three weeks. Following
      treatment period, LFPs were recorded from the left striatum of freely moving rats
      and neuronal cell loss was evaluated by Nissl staining. We found significant
      increase in all frequency bands except delta in saline group when compared with
      vehicle (p < 0.0005), while treatment of oxytocin prevented these alterations in
      EEG recordings. Besides, histopathological evaluation of the striatal sections
      revealed a significant cell loss (p < 0.005), whereas administration of rats with
      oxytocin significantly lessened the neuronal death. These findings suggest that
      injury of dopaminergic neurons triggers exaggerated neuronal oscillations in the
      striatum and oxytocin may have some inhibitory effects on neuronal activity in
      PD. 

PMID- 23970036
TI  - Impact of site-directed mutant luciferase on quantitative green and orange/red
      emission intensities in firefly bioluminescence.
AB  - Firefly bioluminescence has attracted great interest because of its high quantum
      yield and intriguing modifiable colours. Modifications to the structure of the
      enzyme luciferase can change the emission colour of firefly bioluminescence, and
      the mechanism of the colour change has been intensively studied by biochemists,
      structural biologists, optical physicists, and quantum-chemistry theorists. Here,
      we report on the quantitative spectra of firefly bioluminescence catalysed by
      wild-type and four site-directed mutant luciferases. While the mutation caused
      different emission spectra, the spectra differed only in the intensity of the
      green component (lambdamax ~ 560 nm). In contrast, the orange (lambdamax ~ 610
      nm) and red (lambdamax ~ 650 nm) components present in all the spectra were
      almost unaffected by the modifications to the luciferases and changes in pH. Our
      results reveal that the intensity of the green component is the unique factor
      that is influenced by the luciferase structure and other reaction conditions.

PMID- 23970038
TI  - Elucidation of the BACE1 regulating factor GGA3 in Alzheimer's disease.
AB  - Golgi-localized gamma-ear-containing ADP-ribosylation factor-binding protein
      (GGA3) is a central regulator of trafficking and degradation of BACE1 (beta-site
      AbetaPP-cleaving enzyme), the rate-limiting enzyme in the production of amyloid
      beta (Abeta) in Alzheimer's disease (AD). Here, we assessed the potential role of
      GGA3 in AD pathogenesis using independent neuropathological, case-control, and
      family-based human sample cohorts. Increased BACE1 levels coincided with
      decreased GGA3 levels and with elevated phosphorylation status of eIF2alpha-Ser51
      in the temporal cortex of AD patients as compared to age-matched controls.
      Severity of the disease did not alter mRNA or protein levels of GGA3 in the
      inferior temporal cortex of AD patients, while a positive correlation between
      GGA3 and the levels of total, but not phosphorylated, tau was observed.
      Genetically, we did not observe consistent evidence for association between AD
      risk and common GGA3 polymorphisms across a number of independent sample cohorts.
      However, a nominally significant association was observed with rs2242230 (p <
      0.05) among the Finnish case-control cohort. Accordingly, mRNA and protein levels
      of GGA3 in the inferior temporal cortex of AD patients did not significantly
      correlate with rs2242230 genotype status. While the present study indicates that
      GGA3 is involved in the cellular processes relevant for AD pathogenesis, the
      genetic data do not support the idea that common GGA3 polymorphisms would
      contribute to AD risk. 

PMID- 23970040
TI  - Lipopolysaccharide-induced inflammation aggravates irradiation-induced injury to
      the young mouse brain.
AB  - Radiotherapy is an effective treatment strategy in the treatment of brain tumors,
      but it is also a major cause of long-term complications, especially in survivors
      of pediatric brain tumors. Cognitive decline caused by cranial radiotherapy is
      thought, at least partly, to depend on injury to stem and progenitor cells in the
      dentate gyrus of the hippocampus. This study investigated the effects of
      lipopolysaccharide (LPS)-induced inflammation at the time of irradiation (IR) in
      the growing mouse brain. A single injection of LPS (0.3 mg/kg) was administered
      24 h prior to cranial IR of 14-day-old male mice. LPS pretreatment increased the
      levels of the chemokine CCL2 and the cytokine IL-1beta in the brain by 440 and
      560%, respectively, compared to IR alone. IR disrupted hippocampal neurogenesis
      and the growth of the dentate gyrus, and the mice pretreated with LPS displayed
      an even more pronounced lack of growth than the vehicle-treated group 2 months
      after IR. The density of microglia was not affected, but LPS-pretreated mice
      displayed 48% fewer bromodeoxyuridine-positive cells and 43% fewer doublecortin
      positive cells in the granule cell layer 2 months after IR compared with the
      vehicle-treated group. In conclusion, an ongoing inflammation in the brain at the
      time of IR further enhanced the IR-induced loss of neurogenesis, and may
      aggravate future cognitive deficits in patients treated with cranial
      radiotherapy. 

PMID- 23970041
TI  - Burden of anemia in relation to thalassemia and iron deficiency among Vietnamese
      pregnant women.
AB  - BACKGROUND AND AIMS: Information about the extent to which anemia is related to
      thalassemia and iron deficiency (ID) is not available in Vietnam. This study
      investigated the burden of anemia in relation to thalassemia and ID among
      Vietnamese pregnant women. METHODS: A cross-sectional study was conducted in Thua
      Thien Hue, Central Vietnam. Blood samples taken from 399 pregnant women with a
      gestational age <12 weeks were analyzed. Anemia was defined as Hb levels <11
      g/dl, and ID as ferritin values <15 ng/ml. RESULTS: Out of 399 participants, 77
      (19.3%) were anemic. While the prevalence of ID was 20.1%, the prevalence of ID
      anemia was 6.0%. The overall prevalence of thalassemia was 7.3%. Of the 77 anemic
      women, 24 (31.2%) had ID, and 20 (26.0%) had thalassemia genes. The rest (42.9%)
      were anemic due to unknown causes. CONCLUSIONS: The results indicate that ID
      remains a significant health burden among the study population, together with
      anemia caused by unknown factors. Thalassemias appear not to contribute to a
      great extent to anemia among Vietnamese pregnant women. Other causes need to be
      investigated further in order to develop an effective control program for anemia
      within the population.

PMID- 23970042
TI  - Unbound free fatty acids from preterm infants treated with intralipid decouples
      unbound from total bilirubin potentially making phototherapy ineffective.
AB  - Extremely low birth weight (ELBW; <1,000 g) infants have poor outcomes, often
      compromised by bilirubin neurotoxicity. We measured unbound bilirubin (Bf) and
      unbound free fatty acid (FFAu) levels in 5 ELBW infants in a trial examining the
      effects of pharmacologic ductal closure on infants treated with Intralipid
      infusion (3 g/kg/day). The levels for all infants (mean +/- SD) were: total serum
      bilirubin (TSB) 4.6 +/- 1.7 mg/dl, FFAu 376 +/- 496 nM, and Bf 42 +/- 30 nM. Of
      the 3 infants who died, 2 had TSB <5.9 mg/dl but FFAu >580 nM and Bf >75 nM.
      Multiple regression revealed a major effect on Bf levels due to FFAu, indicating
      that Intralipid elevated levels of FFAu and Bf. Indomethacin or ibuprofen reduced
      Bf levels, most likely by reducing FFAu levels through lipase inhibition. Because
      displacement of Bf by FFAu decouples Bf from TSB, phototherapy may not reduce the
      risk of bilirubin or FFAu toxicity in Intralipid-treated ELBW infants. 

PMID- 23970043
TI  - The paraneural compartment: a new destination?

PMID- 23970044
TI  - Burning mouth syndrome: a misunderstood, underinvestigated, and undertreated
      clinical challenge.

PMID- 23970045
TI  - Burning mouth syndrome: current clinical, physiopathologic, and therapeutic data.
AB  - Primary burning mouth syndrome (BMS) is defined as an "intraoral burning for
      which no medical or dental cause was found." Lifetime prevalence ranges from 3.7%
      to 18% - 40% in the elderly. There is no consensus among experts on the
      diagnostic criteria of BMS, the etiology is poorly understood, and there are no
      existing clinical guidelines. Therefore, BMS is often underdiagnosed and its
      management complex. For patients with BMS, this lack of clinical expertise may
      result in decreased quality of life and increased psychological distress.We
      conducted a systematic review to identify clinical features, pathophysiology, and
      therapeutic strategies for BMS. We discuss the multifactorial origin, involving
      peripheral nerve dysfunction and hormonal dysfunction, as well as psychological
      traits. We also describe the results of randomized clinical trials for each
      treatment through a pathophysiologic approach. This review should help clinicians
      recognize BMS, understand its pathophysiology, and gain an enhanced scientific
      understanding of therapeutic alternatives. 

PMID- 23970046
TI  - The European Society of Regional Anaesthesia and Pain Therapy (1982-2012): 30
      years strong.
AB  - Inspired by the earlier establishment of the American Society of Regional
      Anesthesia, but with a structure to accommodate the diverse languages and health
      care systems of Europe, the European Society of Regional Anaesthesia (ESRA) held
      its first scientific meeting in 1982. During the following 30 years, ESRA grew
      from strength to strength and implemented a number of important educational
      initiatives, the story of these developments being the subject of this review.
      ESRA's prime function is to publicize the evidence on regional anesthesia and
      encourage its further development, but it also led the way in democratizing
      European anesthesia societies by being the first to open its membership to all. A
      recent revision of the constitution has further increased the society's
      democratic nature.Educationally, activities grew from a single annual congress to
      include zonal meetings, cadaver workshops, a major online program, and
      collaborations (guidelines and conferences) with other societies. Finally, the
      introduction of a Diploma qualification in regional anesthesia was an entirely
      novel project. 

PMID- 23970047
TI  - Fascia iliaca block for analgesia after hip arthroplasty: a randomized double
      blind, placebo-controlled trial: unsound statistical analysis?

PMID- 23970048
TI  - Reply to Drs Rowley and Emamdee.

PMID- 23970049
TI  - The efficacy of ultrasound-guided fascia iliaca block in hip surgery: a question
      of technique?

PMID- 23970050
TI  - Reply to Dr Murgatroyd et al.

PMID- 23970051
TI  - Is the continuous saphenous block the right technique for postoperative pain
      management after total knee replacement?

PMID- 23970052
TI  - Reply to Dr Chelly.

PMID- 23970053
TI  - Persistent median artery and veins in patients undergoing elective day case hand
      surgery.

PMID- 23970054
TI  - Transverse versus in-plane longitudinal parasagittal plane probe position in
      fascia iliaca block.

PMID- 23970055
TI  - Sciatic nerve structure and nomenclature: epineurium to paraneurium: is this a
      new paradigm?

PMID- 23970056
TI  - Reply to Dr Sala-Blanch et al.

PMID- 23970057
TI  - Continuous spinal labor analgesia in a patient with Hajdu-Cheney syndrome.

PMID- 23970058
TI  - Hourglass-pattern recognition simplifies fascia iliaca compartment block.

PMID- 23970059
TI  - Three recent US patent decisions.

PMID- 23970060
TI  - Serum HE4 levels combined with CE CT imaging improve the management of monitoring
      women affected by epithelial ovarian cancer.
AB  - The aim of the present study was to evaluate human epididymis protein 4 (HE4) as
      a marker of epithelial ovarian cancer (EOC) relapse and the combination of this
      biomarker with contrast-enhanced high-resolution multidetector row computed
      tomography CE CT imaging to impove the monitoring of EOC patients. Twenty-one
      patients with advanced EOC (FIGO III/IV) who underwent surgery and adjuvant
      chemotherapy were retrospectively selected. Each patient contributed 3 serum
      samples drawn at 3-month intervals: time interval I (1-3 months from surgery),
      time interval II (4-6 months from surgery) and time interval III (7-10 months
      from surgery). Serum HE4 and cancer antigen-125 (CA-125) levels were determined
      by EIA and IRMA assays, respectively. Nine out of the 21 (Group A) women had
      disease relapse while 12 out of the 21 (Group B) women had stable disease during
      the follow-up study. Twenty out of the 21 patients underwent at least two CE CT
      follow-ups with an interval time of ~6 months. One patient did not undergo a
      second CE CT. In patients with relapsed EOC, an increase in HE4 was noted in 22,
      78 and 89% of patients within the time intervals I, II and III, respectively.
      Positivity for CA-125 was found later at time interval III and only in 44% of
      patients. Conversely, for EOC patients in remission, increase over the threshold
      level was observed only for marker CA-125 (4/12). The evaluation of imaging
      findings at interval time II showed a significant correlation with high levels of
      HE4 in 6 out of 9 patients with recurrent disease. This study supports the
      hypothesis that HE4 may serve as an early biomarker for recurrence of EOC.
      Moreover, HE4 serum levels combined with CE CT imaging may improve the monitoring
      management of women affected by ovarian cancer. 

PMID- 23970061
TI  - miR-218 is downregulated and directly targets SH3GL1 in childhood
      medulloblastoma.
AB  - An increasing number of studies have suggested that microRNAs (miRNAs) are
      aberrantly expressed in numerous types of tumors and that a deregulation in miRNA
      expression may lead to carcinogenesis. Although miR-218 has been demonstrated to
      be downregulated in several types of cancer, including medulloblastoma (MB), its
      involvement in MB is unclear. In the present study, the expression of miR-218 and
      SH3GL1 were assessed in four MB cell lines and normal cerebellum by qPCR. The
      ectopic expression of miR-218 induced by lentiviral transfection in MB cells on
      proliferation was evaluated by MTT assay, and cell migration and invasion were
      determined by transwell assays. Analysis of the target protein expression and
      related protein expression was determined by western blot analysis. The targeting
      of SH3GL1 by miR-218 was identified using a luciferase reporter assay. The
      results demonstrated that miR-218 was significantly downregulated in MB cell
      lines. MiR-218 significantly inhibited SH3GL1 mRNA and protein expression and
      reduced the luciferase activity of a SH3GL1 3' untranslated region-based
      reporter. Furthermore, overexpression of miR-218 induced by transfection with
      lentivirus significantly suppressed MB cell growth, migration and invasion in
      vitro. Small interfering RNA-mediated SH3GL1 downregulation partially phenocopied
      the effect of miR-218 overexpression in the MB cell lines. The results indicated
      that miR-218 was significantly downregulated in MB cancer cell lines.
      Furthermore, miR-218 functioned as a tumor suppressor by regulating SH3GL1
      expression in MB cancer cells.

PMID- 23970062
TI  - Expression of angiogenic factors in hepatocarcinogenesis: Identification by
      antibody arrays.
AB  - Angiogenesis plays a pivotal role in the progression and metastasis of
      hepatocellular carcinoma (HCC). However, the expression of a wide range of
      angiogenic factors remains obscure in HCC. The purpose of the present study was
      to determine the expression of various angiogenic factors related to
      hepatocarcinogenesis. We examined the expression of 19 angiogenic factors using
      antibody arrays in human tissues of various liver diseases, including HCC. We
      also studied the expression of 19 angiogenic factors in the human HCC cell lines
      PLC/PRF/5, Hep 3B, HuH7, HLE, HLF and Li-7 and the normal hepatocyte cell line
      ACBRI3716. In human tissues, although the expression of acidic fibroblast growth
      factor (aFGF) was found to increase from normal liver to chronic hepatitis, its
      expression remained unchanged in the transition from chronic hepatitis to HCC.
      Vascular endothelial growth factor (VEGF) was elevated in liver cirrhosis, but
      the amounts remained unchanged in the transition from liver cirrhosis to HCC. In
      contrast, either interleukin-8 (IL-8) or basic fibroblast growth factor (bFGF)
      was upregulated in HCC. In the HCC cell lines PLC/PRF/5, Hep 3B and HuH-7, the
      expression of IL-8 was elevated. Although IL-8 was not elevated, bFGF was
      upregulated in the other HCC cell lines HLE, HLF and Li-7. Thus, either IL-8 or
      bFGF was upregulated in HCC cell lines and in HCC tissue samples. These data
      suggest that the upregulation of either IL-8 or bFGF is closely related to the
      transition from liver cirrhosis into HCC. Therefore, the analysis of the
      expression of these cytokines using protein arrays may identify novel therapies
      for individual patients with HCC. 

PMID- 23970063
TI  - Progress in Europe.

PMID- 23970064
TI  - Effect of castration on renal glycosaminoglycans and their urinary excretion in
      male and female rats with chronic renal failure.
AB  - Glycosaminoglycans (GAGs) participate in a variety of processes in the kidney,
      and evidence suggests that gender-related hormones participate in renal function.
      The aim of this study was to analyze the relationship of GAGs, gender, and
      proteinuria in male and female rats with chronic renal failure (CRF). GAGs were
      analyzed in total kidney tissue and 24-h urine of castrated (c), male (M), and
      female (F) Wistar control (C) rats (CM, CMc, CF, CFc) and after 30 days of CRF
      induced by 5/6 nephrectomy (CRFM, CRFMc, CRFF, CRFFc). Total GAG quantification
      and composition were determined using agarose and polyacrylamide gel
      electrophoresis, respectively. Renal GAGs were higher in CF compared to CM. CRFM
      presented an increase in renal GAGs, heparan sulfate (HS), and proteinuria, while
      castration reduced these parameters. However, CRFF and CRFFc groups showed a
      decrease in renal GAGs concomitant with an increase in proteinuria. Our results
      suggest that, in CRFM, sex hormones quantitatively alter GAGs, mainly HS, and
      possibly the glomerular filtration barrier, leading to proteinuria. The lack of
      this response in CRFMc, where HS did not increase, corroborates this theory. This
      pattern was not observed in females. Further studies of CRF are needed to clarify
      gender-dependent differences in HS synthesis. 

PMID- 23970066
TI  - Computed tomography just after endoscopy as the preoperative examination for safe
      percutaneous endoscopic gastrostomy.

PMID- 23970065
TI  - The impact of short daily hemodialysis on anemia and the quality of life in
      Chinese patients.
AB  - Anemia is a frequent complication in hemodialysis patients. Compared to
      conventional hemodialysis (CHD), short daily hemodialysis (sDHD) has been
      reported to be effective in many countries except China. The aim of the present
      study was to determine whether sDHD could improve anemia and quality of life
      (QOL) for Chinese outpatients with end-stage renal disease. Twenty-seven patients
      (16 males/11 females) were converted from CHD to sDHD. All laboratory values were
      measured before conversion (baseline), at 3 months after conversion (sDHD1), and
      at 6 months after conversion (sDHD2). The patient's QOL was evaluated at baseline
      and 6 months after conversion using the Medical Outcomes Study 36-Item Short Form
      Health Survey (SF-36). Hemoglobin concentration increased significantly from
      107.4 +/- 7.9 g/L at baseline to 114.4 +/- 6.8 g/L (P<0.05) at sDHD1, and 118.3+/
      8.4 g/L (P<0.001) at sDHD2 (Student paired t-test). However, the dose requirement
      for erythropoietin decreased from 6847.8 +/- 1057.3 U/week at baseline to
      5869.6+/-1094.6 U/week (P<0.05) at sDHD2. Weekly stdKt/V increased significantly
      from 2.05+/-0.13 at baseline to 2.73+/-0.20 (P<0.001) at sDHD1, and 2.84+/-0.26
      (P<0.001) at sDHD2. C-reactive protein decreased from baseline to sDHD1 and
      sDHD2, but without statistically significant differences. Physical and mental
      health survey scores increased in the 6 months following conversion to sDHD. sDHD
      may increase hemoglobin levels, decrease exogenous erythropoietin dose
      requirements, and improve QOL in Chinese hemodialysis patients compared to CHD. A
      possible mechanism for improvement of clinical outcomes may be optimized
      management of uremia associated with the higher efficiency of sDHD.

PMID- 23970068
TI  - Points to consider for informed consent for genome/exome sequencing.

PMID- 23970067
TI  - Direct characterization of bulk samples by internal extractive electrospray
      ionization mass spectrometry.
AB  - A straight-forward analytical strategy called internal extractive electrospray
      ionization mass spectrometry (iEESI-MS), which combines solvent extraction of
      chemicals inside a bulk sample with in situ electrospray ionization mass
      spectrometry, has been established to directly characterize the interior of a
      bulk sample with molecular specificity. The method allows both qualitative and
      quantitative analysis of analytes distributed in a 3-dimensional volume (e.g., 1
      ~ 100 mm(3)) of various synthetic and biological matrices (e.g., chewing gum,
      leaves, fruits, roots, pork, lung tissues) without either mashing the sample or
      matrix separation. Using different extraction solvents, online chromatographic
      separation of chemicals inside the sample volume was observed during iEESI-MS
      analysis. The presented method is featured by the high speed of analysis, high
      sensitivity, low sample consumption and minimal sample preparation and/or
      degradation, offering unique possibilities for advanced applications in plant
      science, clinical diagnosis, catalyst studies, and materials science.

PMID- 23970069
TI  - Octametallic 4f-phosphonate horseshoes.
AB  - Three octanuclear phosphonate clusters, formulated as [Ln8(O3P(t)Bu)6(MU3
      OH)2(H2O)2(HO(i)Bu)(O2C(t)Bu)12](NH3(i)Pr)2 (Ln = Gd, Dy and Tb), were
      synthesised by refluxing a mixture of pivalic acid (HO2C(t)Bu), Ln(NO3)3.6H2O,
      tert-Butyl phosphonic acid (H2O3P(t)Bu) and isopropylamine ((i)PrNH2) in isobutyl
      alcohol (i)BuOH. 

PMID- 23970070
TI  - Meta-analysis of biodegradable versus durable polymer drug eluting stents in
      coronary artery disease: the reality?

PMID- 23970071
TI  - The 6-minute walking test and all-cause mortality in patients undergoing a post
      cardiac surgery rehabilitation program.
AB  - BACKGROUND: The 6-minute walking test (6mWT) is used to prescribe physical
      activity in cardiac surgery patients. The clinical value of a pre-discharge 6mWT
      and its association with outcome is not well defined. DESIGN AND METHODS: We
      retrospectively analyzed data from 313 patients (age 66 +/- 11 years, 23%
      females, left ventricular ejection fraction (LVEF) 52 +/- 11%, Hb 10.5 +/- 1.3
      g/dl, serum albumin 3.9 +/- 0.4 mg/dl) who were admitted to our rehabilitation
      institute following cardiac surgery. A 6mWT was performed at entry and at
      discharge and expressed as % of theoretical predicted values calculated on the
      basis of individual age, height, weight and sex. The endpoint was represented by
      all-cause mortality. The predictive value of 6mWT was tested in univariate and
      multivariate analysis. RESULTS: A pre-discharge 6mWT was completed by 284 out of
      313 patients. Two patients died in hospital. During a median of 23 months,
      mortality was 9% (26/284) and 44% (12/27) (p < 0.0001) in patients who did or did
      not perform the pre-discharge 6mWT. The distance covered at the pre-discharge
      6mWT as a continuous variable of % predicted values was a significant predictor
      of subsequent mortality (Hazard Ratio (HR) 0.97 (95% CI 0.96-0.99), p = 0.0019).
      After adjustment for all preselected covariates, the pre-discharge 6mWT (HR 0.97
      (95% CI 0.95-0.99), p = 0.0038) and LVEF (HR 0.93 (95% CI 0.90-0.96), p < 0.0001)
      remained significantly associated with the outcome. CONCLUSIONS: In recent
      cardiac surgery patients, the pre-discharge 6mWT is not only a valid measurement
      of the impact of cardiac rehabilitation but also provides outcome information
      offering the possibility to identify patients who may need more intensive follow
      up.

PMID- 23970072
TI  - Electrodeposition of silicon nanotubes at room temperature using ionic liquid.
AB  - Electrodeposition inside an insulated nanoporous template using Room Temperature
      Ionic Liquids (RTILs) has recently been demonstrated as a promising alternative
      technique for synthesizing silicon nanowires due to low cost ambient growth
      conditions. An improvement of the method is shown here to produce Si nanotubes. A
      fine adjustment of electro-chemical parameters influencing ionic diffusion inside
      the nanopores of the template is demonstrated to preferably lead to the growth of
      Si nanotubes at the expense of Si nanowires. This study shows that
      electrodeposition in RTILs is a competitive process to grow high surface to
      volume ratio nanostructures at low cost and over a large scale. It also indicates
      a new prospect for the technique to grow and control nanostructures such as
      radial core-shell nanowires. 

PMID- 23970073
TI  - Isolation, characterization and mapping of genes differentially expressed during
      fibre development between Gossypium hirsutum and G. barbadense by cDNA-SRAP.
AB  - Gossypium hirsutum and G. barbadense are two cultivated tetraploid cotton species
      with differences in fibre quality. The fibre of G. barbadense is longer, stronger
      and finer than that of G. hirsutum. To isolate genes expressed differently
      between the two species during fibre development, cDNA-SRAP (sequence-related
      amplified polymorphism) was applied. This technique was used to analyse genes at
      different stages of fibre development in G. hirsutum cv. Emian22 and G.
      barbadense acc. 3-79, the parents of our interspecific mapping population. A
      total of 4096 SRAP primer combinations were used to screen polymorphism between
      the DNA of the parents, and 275 highly polymorphic primers were picked out to
      analyse DNA and RNA from leaves and fibres at different developmental stages of
      the parents. A total of 168 DNA fragments were isolated from gels and sequenced:
      54, 30, 38 and 41 from fibres of 5, 10, 15 and 20 days post-anthesis,
      respectively, and five from multi stages. To genetically map these sequences, 104
      sequence-specific primers were developed and were used to screened polymorphism
      between the mapping parents. Finally, six markers were mapped on six chromosomes
      of our backbone interspecific genetic map. This work can give us a primary
      knowledge of differences in mechanism of fibre development between G. hirsutum
      and G. barbadense. 

PMID- 23970074
TI  - Fast evolutionary genetic differentiation during experimental colonizations.
AB  - Founder effects during colonization of a novel environment are expected to change
      the genetic composition of populations, leading to differentiation between the
      colonizer population and its source population. Another expected outcome is
      differentiation among populations derived from repeated independent colonizations
      starting from the same source. We have previously detected significant founder
      effects affecting rate of laboratory adaptation among Drosophila subobscura
      laboratory populations derived from the wild. We also showed that during the
      first generations in the laboratory, considerable genetic differentiation occurs
      between foundations. The present study deepens that analysis, taking into account
      the natural sampling hierarchy of six foundations, derived from different
      locations, different years and from two samples in one of the years. We show that
      striking stochastic effects occur in the first two generations of laboratory
      culture, effects that produce immediate differentiation between foundations,
      independent of the source of origin and despite similarity among all founders.
      This divergence is probably due to powerful genetic sampling effects during the
      first few generations of culture in the novel laboratory environment, as a result
      of a significant drop in Ne. Changes in demography as well as high variance in
      reproductive success in the novel environment may contribute to the low values of
      Ne. This study shows that estimates of genetic differentiation between natural
      populations may be accurate when based on the initial samples collected in the
      wild, though considerable genetic differentiation may occur in the very first
      generations of evolution in a new, confined environment. Rapid and significant
      evolutionary changes can thus occur during the early generations of a founding
      event, both in the wild and under domestication, effects of interest for both
      scientific and conservation purposes. 

PMID- 23970075
TI  - Preservation of Solanum pimpinellifolium genomic fragments in recombinant
      genotypes improved the fruit quality of tomato.
AB  - Five recombinant inbred lines obtained from the F2 generation of an interspecific
      cross between cultivar, Caimanta (Cai, Solanum lycopersicum) and wild accession,
      LA722 (P, S. pimpinellifolium) were crossed to obtain the second cycle hybrids
      (SCH). Eleven fruit quality traits were assessed in evaluating phenotypic
      variability among genotypes P, Cai, F1 (Cai x P), five RILs, and 10 SCH. One of
      the five recombinant inbred lines and three SCH had higher values than P, as the
      best genotype for shelf life. Sequence-related amplified polymorphism was used as
      the molecular method for detecting polymorphism among these 18 genotypes. The
      percentage of polymorphism in RILs and SCH was 61% and 66% respectively.
      Moreover, some bands detected in P were present in SCH. Several multivariate
      analyses were performed to find agreement between the phenotypic variability
      observed for fruit quality traits and the polymorphism obtained from sequence
      related amplified polymorphism markers. A general Procrustes analysis estimated
      that there was a consensus proportion of 75% between phenotypic and molecular
      data. There was considerable preservation of some bands from the wild genotype,
      which could increase the variability in fruit quality traits in populations where
      the genetic diversity is limited. 

PMID- 23970076
TI  - Preliminary genetic linkage maps of Chinese herb Dendrobium nobile and D.
      moniliforme.
AB  - Dendrobium is an endangered genus in the orchid family with medicinal and
      horticultural value. Two preliminary genetic linkage maps were constructed using
      90 F1 progeny individuals derived from an interspecific cross between D. nobile
      and D. moniliforme (both, 2n = 38), using random amplified polymorphic DNA (RAPD)
      and intersimple sequence repeat (ISSR). A total of 286 RAPD loci and 68 ISSR loci
      were identified and used for genetic linkage analysis. Maps were constructed by
      double pseudo-testcross mapping strategy using the software Mapmaker/EXP ver.
      3.0, and Kosambi map distances were constructed using a LOD score greater than or
      equal to 4 and a recombination threshold of 0.4. The resulting frame map of D.
      nobile was 1474 cM in total length with 116 loci distributed in 15 linkage
      groups; and the D. moniliforme linkage map had 117 loci placed in 16 linkage
      groups spanning 1326.5 cM. Both maps showed 76.91% and 73.59% genome coverage for
      D. nobile and D. moniliforme, respectively. These primary maps provide an
      important basis for genetic studies and further medicinal and horticultural
      traits mapping and marker-assisted selection in Dendrobium breeding programmes. 

PMID- 23970077
TI  - Conditional and unconditional QTL mapping of drought-tolerance-related traits of
      wheat seedling using two related RIL populations.
AB  - For discovering the quantitative trait loci (QTLs) contributing to early seedling
      growth and drought tolerance during germination, conditional and unconditional
      analyses of 12 traits of wheat seedlings: coleoptile length, seedling height,
      longest root length, root number, seedling fresh weight, stem and leaves fresh
      weight, root fresh weight, seedling dry weight, stem and leaves dry weight, root
      dry weight, root to shoot fresh weight ratio, root-to-shoot dry weight ratio,
      were conducted under two water conditions using two F8:9 recombinant inbred line
      (RIL) populations. The results of unconditional analysis are as follows: 88 QTLs
      accounting for 3.33-77.01% of the phenotypic variations were detected on
      chromosomes 1A, 1B, 1D, 2A, 2B, 2D, 3A, 3B, 4A, 4B, 4D, 5A, 5B, 5D, 6A, 6B, 6D,
      7A, 7B and 7D. Among these QTLs, 19 were main-effect QTLs with a contribution
      rate greater than 10%. The results of the conditional QTL analysis of 12 traits
      under osmotic stress on normal water conditions were as follows: altogether 22
      QTLs concerned with drought tolerance were detected on chromosomes 1B, 2A, 2B,
      3B, 4A, 5D, 6A, 6D, 7B, and 7D. Of these QTLs, six were main-effect QTLs. These
      22 QTLs were all special loci directly concerned with drought tolerance and most
      of them could not be detected by unconditional analysis. The finding of these
      QTLs has an important significance for fine-mapping technique, map-based cloning,
      and molecular marker-assisted selection of early seedling traits, such as growth
      and drought tolerance. 

PMID- 23970078
TI  - Chromosomal location of genomic SSR markers associated with yellow rust
      resistance in Turkish bread wheat (Triticum aestivum L.).
AB  - We have previously reported Xgwm382 as a diagnostic marker for disease resistance
      against yellow rust in Izgi2001 x ES14 F2 population. Among the same earlier
      tested 230 primers, one SSR marker (Xgwm311) also amplified a fragment which is
      present in the resistant parent and in the resistant bulks, but absent in the
      susceptible parent and in the susceptible bulks. To understand the chromosome
      group location of these diagnostic markers, Xgwm382 and Xgwm311, in the same
      population, we selected 16 SSR markers mapped only in one genome of chromosome
      group 2 around 1-21 cM distance to these diagnostic markers based on the SSR
      consensus map of wheat. Out of 16 SSRs, Xwmc658 identified resistant F2
      individuals as a diagnostic marker for yellow rust disease and provided the
      location of Xgwm382 and Xgwm311 on chromosome 2AL in our plant material. 

PMID- 23970079
TI  - Quality of synthetic hexaploid wheat containing null alleles at Glu-A1 and Glu-B1
      loci.
AB  - Triticum turgidum ssp. dicoccon PI94668 and PI349045 were identified as
      containing null alleles at Glu-A1 and Glu-B1 loci in previous investigation.
      Sequencing of the respective HMW-GS genes Ax, Bx, Ay and By in both accessions
      indicated equal DNA lengths with gene silencing caused by 1 to 4 in-frame stop
      codon(s) in the open reading frames. Six synthetic hexaploid wheat lines were
      produced by crossing PI94668 or PI349045 with six Aegilops tauschii by
      spontaneous chromosome doubling of unreduced gametes. As expected, these
      amphiploids had three different HMW-GS: Dx 3.1(t) + Dy11(*t), Dx2.1(t) +10(t) and
      Dx2(t) +Dy12(t) in Glu-D1 but double nulls in Glu-A1 and Glu-B1. Quality tests
      showed that most quality parameters in two T. turgidum ssp. dicoccon parents were
      very low due to the lack of HMW-GSs. However, incorporation of HMW-GS from Ae.
      tauschii in six synthetic hexaploid wheat lines significantly increased most
      quality related parameters. The potential values of these wheat lines in
      improving the quality of wheat are discussed. 

PMID- 23970080
TI  - The first complete mitochondrial genome from Bostrychus genus (Bostrychus
      sinensis) and partitioned Bayesian analysis of Eleotridae fish phylogeny.
AB  - To understand the phylogenetic position of Bostrychus sinensis in Eleotridae and
      the phylogenetic relationships of the family, we determined the nucleotide
      sequence of the mitochondrial (mt) genome of Bostrychus sinensis. It is the first
      complete mitochondrial genome sequence of Bostrychus genus. The entire mtDNA
      sequence was 16508 bp in length with a standard set of 13 protein-coding genes,
      22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs) and a noncoding
      control region. The mitochondrial genome of B. sinensis had common features with
      those of other bony fishes with respect to gene arrangement, base composition,
      and tRNA structures. Phylogenetic hypotheses within Eleotridae fish have been
      controversial at the genus level. We used the mitochondrial cytochrome b (cytb)
      gene sequence to examine phylogenetic relationships of Eleotridae by using
      partitioned Bayesian method. When the specific models and parameter estimates
      were presumed for partitioning the total data, the harmonic mean -lnL was
      improved. The phylogenetic analysis supported the monophyly of Hypseleotris and
      Gobiomorphs. In addition, the Bostrychus were most closely related to Ophiocara,
      and the Philypnodon is also the sister to Microphlypnus, based on the current
      datasets. Further, extensive taxonomic sampling and more molecular information
      are needed to confirm the phylogenetic relationships in Eleotridae. 

PMID- 23970081
TI  - Distribution pattern of histone H3 phosphorylation at serine 10 during mitosis
      and meiosis in Brachiaria species.
AB  - Histones are the major eukaryotic DNA-binding proteins. Posttranslational
      modifications on N-terminal tails of histones that form nucleosomes are often
      associated with distinct biological functions. Some theories suggest that one of
      these modifications, the phosphorylation of histone H3 at serine 10 (H3S10ph)
      plays a role in both chromosome condensation and sister chromatid cohesion.
      Although histones and some of their modifications are highly conserved, studies
      have shown that role and distribution of H3S10ph may differ between species. We
      evaluated the pattern of H3 phosphorylation using immunodetection during mitosis
      and meiosis in both diploid and tetraploid genotypes of Brachiaria species.
      Results revealed differences in chromosome distribution of H3S10ph when mitosis
      and meiosis were compared. Whole chromosomes were phosphorylated during meiosis
      I, whereas phosphorylation was restricted to the pericentromeric region in both
      meiosis II and mitosis. There was no variation in phosphorylation patterns
      between Brachiaria species and diploid and tetraploid genotypes. Regarding
      spatiotemporal coordination in the Brachiaria species evaluated, H3S10ph is
      related to maintenance of sister chromatid cohesion during cell divisions. 

PMID- 23970082
TI  - Genetic analysis and location of gene for resistance to stripe rust in wheat
      international differential host Strubes Dickkopf.
AB  - Strubes Dickkopf is the sixth differential in the world set for wheat stripe
      (yellow) rust. It is very important to clarify its genetic character of
      resistance to stripe rust and to develop the molecular markers linked to
      resistance genes. The NIL Taichung 29*6/Strubes Dickkopf, which was obtained by
      Strubes Dickkopf as the gene donor and Taichung 29 as the genetic background
      through backcross breeding, was crossed with the recurrent parent Taichung 29,
      inbred, and backcrossed to obtain the F1, F2 and BC1 population. The genetic
      analysis of the cross Taichung 29/(Taichung 29*6/Strubes Dickkopf) was assessed
      by inoculating the rust race CYR26 at seedling stage. Bulked segregant analysis
      (BSA) and F2 segregation analysis were used for detecting polymorphic primers to
      locate the gene. The resistance of the NIL Taichung 29*6/Strubes Dickkopf to
      CYR26 was controlled by a single dominant gene, named YrSD. The primer pair
      Xbarc59 on 5B was linked to YrSD and the genetic distance between Xbarc59 and
      YrSD was 2.4 cM. The molecular marker Xbarc59 closely linked to the gene YrSD
      could be used in marker-assisted selection for resistance to stripe rust in wheat
      breeding programmes. 

PMID- 23970083
TI  - Genetic diversity studies and identification of SSR markers associated with
      Fusarium wilt (Fusarium udum) resistance in cultivated pigeonpea (Cajanus cajan).
AB  - Genetic diversity and identification of simple sequence repeat markers correlated
      with Fusarium wilt resistance was performed in a set of 36 elite cultivated
      pigeonpea genotypes differing in levels of resistance to Fusarium wilt. Twenty
      four polymorphic sequence repeat markers were screened across these genotypes,
      and amplified a total of 59 alleles with an average high polymorphic information
      content value of 0.52. Cluster analysis, done by UPGMA and PCA, grouped the 36
      pigeonpea genotypes into two main clusters according to their Fusarium wilt
      reaction. Based on the Kruskal-Wallis ANOVA and simple regression analysis, six
      simple sequence repeat markers were found to be significantly associated with
      Fusarium wilt resistance. The phenotypic variation explained by these markers
      ranged from 23.7 to 56.4%. The present study helps in finding out feasibility of
      prescreened SSR markers to be used in genetic diversity analysis and their
      potential association with disease resistance. 

PMID- 23970084
TI  - QTL mapping and correlation analysis for 1000-grain weight and percentage of
      grains with chalkiness in rice.
AB  - The study of 1000-grain weight (TGW) and percentage of grains with chalkiness
      (PGWC) is very important in rice. In this study, a set of introgression lines
      (ILs), derived from Sasanishiki/Habataki with Sasanishiki as the recurrent
      parent, were used to detect correlations and quantitative trait loci (QTL) on TGW
      and PGWC in two different environments. Phenotypic correlation analysis showed
      that there was no significant correlation between TGW and PGWC in both
      environments, which indicated that the linkage of TGW and PGWC traits could be
      broken via suitable population. A total of 20 QTL were detected in both
      environments, nine QTL for 1000-paddy-grain weight (PTGW), five QTL for 1000
      brown-grain weight (BTGW) and six QTL for percentage of grains with chalkiness
      (PGWC). Moreover, five QTL, qPTGW3, qPTGW8.2, qPTGW11.1 for PTGW and qPGWC1.1,
      qPGWC1.2 for PGWC, were stably expressed in both environments. Phenotypic values
      were significantly different (P < 0.01) between the introgression lines carrying
      these five QTL alleles and the genetic background parent, Sasanishiki. The
      introgression lines carrying these QTL also represent a useful genetic resource
      in the context of rice yield and quality improvement via a design-breeding
      approach. 

PMID- 23970085
TI  - Strong association of the SNP rs17822931 with wet earwax and bromhidrosis in a
      Chinese family.

PMID- 23970086
TI  - Molecular markers unravel intraspecific and interspecific genetic variability in
      Plantago ovata and some of its wild allies.

PMID- 23970087
TI  - The partial mitochondrial sequence of the Old World stingless bee, Tetragonula
      pagdeni.

PMID- 23970088
TI  - Analysis of MC1R variants in Indian oculocutaneous albinism patients:
      highlighting the risk of skin cancer among albinos.

PMID- 23970089
TI  - Last mated male sperm precedence in doubly mated females is not ubiquitous:
      evidence from sperm competition in laboratory populations of Drosophila nasuta
      nasuta and Drosophila nasuta albomicans.

PMID- 23970090
TI  - A mother with variant Turner syndrome and two daughters with trisomy X: a case
      report.

PMID- 23970091
TI  - Inheritance of blast resistance and identification of SSR marker associated with
      it in rice cultivar RDN 98-2.

PMID- 23970092
TI  - Genetics of early growth vigour in lentil (Lens culinaris Medik.).

PMID- 23970093
TI  - A comparative study of the molecular evolution of signalling pathway members
      across olfactory, gustatory and photosensory modalities.

PMID- 23970095
TI  - Acute hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency
      complicated by Ginkgo biloba.
AB  - We report on a patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency
      who developed acute hemolytic anemia after having received an injection of Ginkgo
      biloba for dementia prophylaxis without medical advice. She suddenly developed
      general malaise, generalized yellowish skin color, and tea-colored urine.
      Intravenous fluid infusion and cessation of G. biloba quickly relieved her
      clinical symptoms. To the best of our knowledge, this is the first case report of
      G. biloba-induced acute hemolytic anemia in vivo.

PMID- 23970094
TI  - Search for missing schizophrenia genes will require a new developmental
      neurogenomic perspective.
AB  - Even the most powerful experimental designs in search of genetic causes of
      schizophrenia have not met the desired goal. It is imperative to review the
      reasons for such an outcome and to formulate novel strategies for the future
      direction of this research in the new era of individual genomes. Here, we will
      review aspects of neurodevelopmental hypothesis of schizophrenia in the light of
      novel genomic and epigenomic insights. Specifically, we will argue for the
      involvement of de novo mutations and epigenetic modifications during
      neurodevelopment that may result in schizophrenia. Our conclusion is that the
      successful elucidation of hereditary mechanisms in neuropsychiatric disorders
      must begin with attention to discrete endophenotypes; consideration of ontogeny,
      forethought of genome structure including temporal and spatial patterns of (epi)
      mutations and the use of judicious techniques that go beyond association studies.

PMID- 23970096
TI  - Mutation of TGF-beta receptor II facilitates human bladder cancer progression
      through altered TGF-beta1 signaling pathway.
AB  - Tumor cells commonly adapt survival strategies by downregulation or mutational
      inactivation of TGF-beta receptors thereby reversing TGF-beta1-mediated growth
      arrest. However, TGF-beta1-triggered signaling also has a protumor effect through
      promotion of tumor cell migration. The mechanism(s) through which malignant cells
      reconcile this conflict by avoiding growth arrest, but strengthening migration
      remains largely unclear. TGF-betaRII was overexpressed in the bladder cancer cell
      line T24, concomitant with point mutations, especially the Glu269 to Lys mutation
      (G -> A). Whilst leaving Smad2/3 binding unaffected, TGF-betaRII mutations
      resulted in the unaffected tumor cell growth and also enhanced cell mobility by
      TGF-beta1 engagement. Such phenomena are perhaps partially explained by the
      mutated TGF-betaRII pathway deregulating the p15 and Cdc25A genes that are
      important to cell proliferation and CUTL1 gene relevant to motility. On the other
      hand, transfecting recombinant TGF-betaRII-Fc vectors or smad2/3 siRNA blocked
      such abnormal gene expressions. Clinically, such G -> A mutations were also found
      in 18 patients (n=46) with bladder cancer. Comparing the clinical and pathologic
      characteristics, the pathologic T category (chi2 trend = 7.404, P<0.01) and tumor
      grade (chi2 trend = 9.127, P<0.01) tended to increase in the G -> A mutated group
      (TGF-betaRII point-mutated group). These findings provide new insights into how
      TGF-beta1 signaling is tailored during tumorigenesis and new information into the
      current TGF-beta1-based therapeutic strategies, especially in bladder cancer
      patient treatment.

PMID- 23970097
TI  - Possible role of dynorphins in Alzheimer's disease and age-related cognitive
      deficits.
AB  - BACKGROUND/AIMS: Expression of dynorphin, an endogenous opioid peptide, increases
      with age and has been associated with cognitive deficits in rodents. Elevated
      dynorphin levels have been reported in postmortem samples from Alzheimer's
      disease (AD) patients, and prodynorphin (PDYN) gene polymorphisms might be linked
      to cognitive function in the elderly. Activation of kappa-opioid receptors by
      dynorphins has been associated with stress-related memory impairments.
      Interestingly, these peptides can also modulate glutamate neurotransmission and
      may affect synaptic plasticity underlying memory formation. N-methyl-D-aspartate
      (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazol-propionate (AMPA) ionotropic
      glutamate receptor levels generally decrease with aging, and their function is
      impaired in AD. METHODS: Here, we compared the impact of aging on ionotropic
      glutamate receptor levels in the hippocampal formation of wild-type (WT) and Pdyn
      knock-out (KO) mice. RESULTS: We observed a significant reduction in GluR1 and
      GluR2 AMPA receptor subunits in the hippocampal formation of 18- to 25-month-old
      WT mice in comparison with 6-month-old mice. Conversely, the GluR1 protein level
      was maintained in old Pdyn KO mice, and the NMDA NR2B subunit level was increased
      by 42% when compared to old WT animals. CONCLUSIONS: These results suggest that
      elevated dynorphin expression occurring during aging and AD may mediate cognitive
      deficits by altering the glutamatergic system integrity.

PMID- 23970098
TI  - The stable microbubble test for determining continuous positive airway pressure
      (CPAP) success in very preterm infants receiving nasal CPAP from birth.
AB  - BACKGROUND: Very preterm infants can be treated with nasal continuous positive
      airway pressure (CPAP) from birth, but some fail. A rapid test, such as the
      stable microbubble test (SMT) on gastric aspirate, may identify those who can be
      managed successfully using CPAP. OBJECTIVE: To determine if SMT can identify soon
      after birth, very preterm infants who may be successfully managed on CPAP alone.
      METHODS: Stable microbubbles (diameter <15 um) were counted in gastric aspirates
      taken <1 h of age from infants <30 weeks' gestation, who received CPAP from
      birth. Infants failed CPAP if intubated at <72 h of age. Clinicians were masked
      to SMT results. A receiver operating characteristic curve was generated to
      determine the relationship between number of microbubbles/mm(2) and subsequent
      intubation. RESULTS: 68 infants of mean (SD) 28.1 (1.4) weeks' gestation received
      CPAP in the delivery room at a median (interquartile range) pressure 7 (6-8)
      cmH2O and FiO2 0.25 (0.21-0.3). Gastric aspirates were taken at a median
      (interquartile range) age of 0.5 (0.3-0.6) hours. The best cut-off point for
      predicting CPAP success or failure was a SMT count of 8 microbubbles/mm(2). The
      area under the receiver operating characteristic curve was 0.8 (95% CI 0.7-0.9).
      A SMT count >=8 microbubbles/mm(2) had a sensitivity of 53%, a specificity of
      100%, a positive predictive value of 100%, and a negative predictive value of 60%
      for predicting CPAP success. CONCLUSION: Infants treated with CPAP from birth,
      who had SMT counts >=8 microbubbles/mm(2) on their gastric aspirate, did not fail
      CPAP.

PMID- 23970099
TI  - microRNA-223 promotes the growth and invasion of glioblastoma cells by targeting
      tumor suppressor PAX6.
AB  - Glioblastoma is the most common primary central nervous system malignancy and its
      unique invasiveness hinders effective treatment. Its high invasiveness may be
      controlled partly by microRNAs (miRNAs, miRs) and their target genes. In the
      present study, we found that increased miR-223 expression and reduced PAX6
      expression coexisted in glioblastoma as detected by quantitative PCR or tissue
      microarrays. We confirmed that miR-223 directly targets PAX6 through binding to
      its 3'-UTR using dual luciferase reporter assay. In U251 and U373 glioblastoma
      cells, overexpression of miR-223 decreased PAX6 mRNA and protein expression;
      however, inhibition of miR-223 increased PAX6 mRNA and protein expression.
      Moreover, overexpression of miR-223 led to effects similar to those of PAX6
      knockdown: increased cell viability, increased percentage of cells in the G1
      phase and increased cell invasiveness parallel with increased MMP2, MMP9 and
      VEGFA expression. In addition, inhibition of miR-223 resulted in effects similar
      to those of PAX6 overexpression: decreased cell viability, decreased percentage
      of cells in the G1 phase and decreased cell invasiveness parallel with reduced
      MMP2, MMP9 and VEGFA expression. The data presented here suggest that miR-223
      promotes the growth and invasion of U251 and U373 glioblastoma cells by targeting
      PAX6, which serves as a tumor suppressor in glioblastoma exerting the functions
      of inhibition of cell cycle transition, and the expression of MMP2, MMP9 and
      VEGFA. In conclusion, the present study supports miR-223 and PAX6 as novel
      therapeutic targets for glioblastoma. 

PMID- 23970100
TI  - Prognostic scores for early stratification of septic patients admitted to an
      emergency department-high dependency unit.
AB  - OBJECTIVES: The aim of this study was to identify a reliable tool for the early
      prognostic stratification of septic patients admitted to the emergency department
      high dependency unit (ED-HDU), a clinical setting providing a subintensive level
      of care; we also estimated the cost saving associated with HDU stay compared with
      ICU stay. MATERIALS AND METHODS: Mortality in Emergency Department Sepsis (MEDS),
      Acute Physiology Age Chronic Health Evaluation II (APACHE II), Simplified Acute
      Physiology Score II (SAPS II), Sequential Organ Failure Assessment (SOFA) score
      (SOFA-T0) and the Charlson index were calculated at ED admission. SOFA score was
      also calculated after 24 h (SOFA-T1). The primary outcome was 28 days mortality.
      RESULTS: We admitted 140 patients with severe sepsis or septic shock in our ED
      HDU from June 2008 to December 2010; 135 were included in the study. One month's
      mortality was 29%. SOFA-T1 was significantly higher in patients who needed an ICU
      admission (7.5+/-3.8 vs. 5.3+/-3.0, P=0.048); it also showed the best mortality
      prediction ability (area under the curve 0.80, 95% confidence interval 0.70
      0.91), compared with MEDS, SAPS, and APACHE score. Troponin and procalcitonin
      evaluated at ED admission and after 24 h did not show significant differences
      according to prognosis; patients with lactate more than 2 showed a higher
      mortality (40 vs. 22%, P=0.034). In a regression analysis adjusted for age,
      lactate value, and the Charlson index, SOFA-T1 (RR 1.551, 95% confidence interval
      1.204-1.998, P<0.001) maintained an independent prognostic value for 28 days
      mortality. During the 267 days of stay at the ED-HDU, the total saving was
      &OV0556;460 041, compared with the cost of the same period in the ICU.
      CONCLUSION: SOFA score is a feasible and accurate tool for an early risk
      stratification of septic patients admitted to the ED-HDU.

PMID- 23970101
TI  - Overexpression of CENP-H as a novel prognostic biomarker for human hepatocellular
      carcinoma progression and patient survival.
AB  - Centromere protein H (CENP-H) has been shown to be significantly upregulated in
      many types of cancers and is associated with disrupted cell cycle regulation,
      cell proliferation and genetic instability. The aim of the present study was to
      explore the expression and localization of CENP-H in hepatocellular carcinoma
      (HCC) and determine whether its overexpression is a prognostic biomarker for HCC.
      Reverse transcription-polymerase chain reaction (pcr), real-time qPCR and western
      blotting were used to compare CENP-H expression at the mRNA and protein levels in
      HCC samples and corresponding adjacent non-cancerous samples. CENP-H protein
      levels were determined in 60 paired paraffin-embedded HCC tissues using
      immunohistochemistry (IHC), and the correlation with clinicopathological features
      and patient prognosis was analyzed. In addition, an immunofluorescence assay was
      performed to test the expression and localization of CENP-H protein in HCC cells.
      Results showed that levels of CENP-H mRNA and protein were higher in HCC samples
      than in the corresponding adjacent non-cancerous samples. In 60 paired paraffin
      embedded tissues, CENP-H was upregulated in the HCC samples (38/60, 63.3%)
      relative to the adjacent non-cancerous samples (21/60, 35%, P=0.003), and a
      higher level of upregulation was associated with tumor size (P=0.032); higher
      histological grade (P=0.001); more advanced TNM stage (P=0.002) and Chinese
      clinical stage (P=0.008); and poorer prognosis. In addition, consistent with the
      results of IHC, the immunofluorescence assay showed that CENP-H was localized in
      the nucleus of Hep3B cells. CENP-H was overexpressed in HCC, and its level of
      upregulation was an independent prognostic indicator, suggesting that CENP-H may
      be an effective therapeutic strategy for the treatment of HCC. 

PMID- 23970102
TI  - Alantolactone induces apoptosis in RKO cells through the generation of reactive
      oxygen species and the mitochondrial pathway.
AB  - Alantolactone, a methanol extract of Inula helenium, possesses anticancer
      properties in a number of cancer cell lines. However, its anticancer effect on
      human colorectal cancer cells and the underlying mechanisms remain to be
      elucidated. In the present study, the effects of alantolactone on cell viability
      and apoptosis in RKO human colon cancer cells were investigated. Alantolactone
      treatment of RKO cells was found to result in dose-dependent inhibition of cell
      viability and induction of apoptosis, accompanied with the accumulation of
      reactive oxygen species (ROS) and the disruption of mitochondrial membrane
      potential. In addition, these effects were blocked with N-acetylcysteine, a
      specific ROS inhibitor. Western blotting indicated that exposure of RKO cells to
      alantolactone is associated with the downregulation of Bcl-2, induction of Bax
      and activation of caspase-3 and -9. These results indicated that a ROS-mediated
      mitochondria-dependent pathway is involved in alantolactone-induced apoptosis.
      From these observations, it was hypothesized that alantolactone may be used for
      the treatment of human colon cancer.

PMID- 23970103
TI  - SUMOylation negatively modulates target gene occupancy of the KDM5B, a histone
      lysine demethylase.
AB  - The histone lysine demethylase KDM5B plays key roles in gene repression by
      demethylating trimethylated lysine 4 of histone H3 (H3K4me3), a modification
      commonly found at the promoter region of actively transcribed genes. KDM5B is
      known to regulate the expression of genes involved in cell cycle progression;
      however, little is known about the post-translational modifications that regulate
      KDM5B. Herein, we report that KDM5B is SUMOylated at lysine residues 242 and 278
      and that the ectopic expression of the hPC2 SUMO E3 ligase enhances this
      SUMOylation. Interestingly, the levels of KDM5B and its SUMOylated forms are
      regulated during the cell cycle. KDM5B is modulated by RNF4, an E3 ubiquitin
      ligase that targets SUMO-modified proteins to proteasomal degradation. Digital
      gene expression analyses showed that cells expressing the SUMOylation-deficient
      KDM5B harbor repressed mRNA expression profiles of cell cycle and DNA repair
      genes. Chromatin immunoprecipitations confirmed some of these genes as KDM5B
      targets, as they displayed reduced H3K4me3 levels in cells ectopically expressing
      KDM5B. We propose that SUMOylation by hPC2 regulates the activity of KDM5B. 

PMID- 23970104
TI  - Cortical network properties revealed by SSVEP in anesthetized rats.
AB  - Steady state visual evoked potentials (SSVEP) are assumed to be regulated by
      multiple brain areas, yet the underlying mechanisms are not well understood. In
      this study, we utilized multi-channel intracranial recordings together with
      network analysis to investigate the underlying relationships between SSVEP and
      brain networks in anesthetized rat. We examined the relationship between SSVEP
      amplitude and the network topological properties for different stimulation
      frequencies, the synergetic dynamic changes of the amplitude and topological
      properties in each rat, the network properties of the control state, and the
      individual difference of SSVEP network attributes existing among rats. All these
      aspects consistently indicate that SSVEP response is closely correlated with
      network properties, the reorganization of the background network plays a crucial
      role in SSVEP production, and the background network may provide a physiological
      marker for evaluating the potential of SSVEP generation. 

PMID- 23970105
TI  - Dichotomizing sensory nerve fibers innervating both the lumbar vertebral body and
      the area surrounding the iliac crest: a possible mechanism of referred lateral
      back pain from lumbar vertebral body.
AB  - STUDY DESIGN: Animal study. OBJECTIVE: To determine the existence of
      dichotomizing sensory nerve fibers innervating both the lumbar vertebral body and
      the area surrounding the iliac crest (ASIC). SUMMARY OF BACKGROUND DATA: Elderly
      patients with osteoporosis sometimes experience lumbar vertebral fracture and may
      feel diffuse nonlocalized pain in the back, the lateral portion of the trunk, and
      the ASIC. The pattern of sensory innervation of vertebral bodies remains unclear.
      DRG neurons with dichotomizing axons have been reported and are thought to be
      related to referred pain. The purpose of this study was to investigate the
      existence of dichotomizing axons to the lumbar vertebral bodies and the ASIC in
      rats. METHODS: Two kinds of neurotracers (1,1'-dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate [DiI] and Fluoro-Gold [FG]) were used.
      DiI crystals were placed in the left ASIC, and FG was applied into the L2
      vertebral body in 10 rats. Four weeks later, left DRGs from L1 to L6 were
      resected, sectioned, and observed under a fluorescence microscope. RESULTS: DiI
      labeled DRG neurons innervating the ASIC and FG-labeled DRG neurons innervating
      the vertebral L2 body were distributed from L1 to L6. The ratio of total double
      labeled per total DiI-labeled DRG neurons was 10.2%, and that of total double
      labeled per total FG-labeled DRG neurons was 14.7%. These double-labeled DRG
      neurons innervating the L2 vertebral body had other axons that extended to the
      ASIC. CONCLUSION: This finding provides a possible neuroanatomical explanation
      for referred pain in the ASIC from vertebral bodies.

PMID- 23970106
TI  - Lumbar disc nomenclature: version 2.0: recommendations of the combined task
      forces of the North American Spine Society, the American Society of Spine
      Radiology, and the American Society of Neuroradiology.
AB  - STUDY DESIGN: This article comprises a review of the literature pertaining to the
      normal and pathological lumbar disc and the compilation of a standardized
      nomenclature. OBJECTIVE: To provide a resource that promotes a clear
      understanding of lumbar disc terminology among clinicians, radiologists, and
      researchers. SUMMARY OF BACKGROUND DATA: The article "Nomenclature and
      Classification of Lumbar Disc Pathology. Recommendations of the Combined Task
      Forces of the North American Spine Society, American Society of Spine Radiology
      and American Society of Neuroradiology" was published in 2001 in Spine (c)
      Lippincott, Williams and Wilkins and formally endorsed by the 3 boards. Its
      purpose, which it served for well over a decade, was to promote greater clarity
      and consistency of usage of spine terminology. Since 2001, there has been
      sufficient evolution in our understanding of the lumbar disc to suggest the need
      for revision and updating. The document represents the consensus recommendations
      of the current combined task forces and reflects changes consistent with current
      concepts in radiological and clinical care. METHODS: A PubMed search was
      performed for literature pertaining to the lumbar disc. The task force members
      individually and collectively reviewed the literature and revised the 2001
      document. It was then reviewed by the governing boards of the American Society of
      Spine Radiology, the American Society of Neuroradiology, and the North American
      Spine Society. After further revision based on their feedback, the paper was
      approved for publication. RESULTS: The article provides a discussion of the
      recommended diagnostic categories and a glossary of terms pertaining to the
      lumbar disc, a detailed discussion of the terms and their recommended usage, as
      well as updated illustrations and literature references. CONCLUSION: We have
      revised and updated a document that, since 2001, has provided a widely accepted
      nomenclature that helps maintain consistency and accuracy in the description of
      the properties of the normal and abnormal lumbar discs and that serves as a
      system for classification and reporting built upon that nomenclature.

PMID- 23970107
TI  - AOSpine thoracolumbar spine injury classification system: fracture description,
      neurological status, and key modifiers.
AB  - STUDY DESIGN: Reliability and agreement study, retrospective case series.
      OBJECTIVE: To develop a widely accepted, comprehensive yet simple classification
      system with clinically acceptable intra- and interobserver reliability for use in
      both clinical practice and research. SUMMARY OF BACKGROUND DATA: Although the
      Magerl classification and thoracolumbar injury classification system (TLICS) are
      both well-known schemes to describe thoracolumbar (TL) fractures, no TL injury
      classification system has achieved universal international adoption. This lack of
      consensus limits communication between clinicians and researchers complicating
      the study of these injuries and the development of treatment algorithms. METHODS:
      A simple and reproducible classification system of TL injuries was developed
      using a structured international consensus process. This classification system
      consists of a morphologic classification of the fracture, a grading system for
      the neurological status, and description of relevant patient-specific modifiers.
      Forty cases with a broad range of injuries were classified independently twice by
      group members 1 month apart and analyzed for classification reliability using the
      Kappa coefficient (kappa). RESULTS: The morphologic classification is based on 3
      main injury patterns: type A (compression), type B (tension band disruption), and
      type C (displacement/translation) injuries. Reliability in the identification of
      a morphologic injury type was substantial (kappa= 0.72). CONCLUSION: The AOSpine
      TL injury classification system is clinically relevant according to the consensus
      agreement of our international team of spine trauma experts. Final evaluation
      data showed reasonable reliability and accuracy, but further clinical validation
      of the proposed system requires prospective observational data collection
      documenting use of the classification system, therapeutic decision making, and
      clinical follow-up evaluation by a large number of surgeons from different
      countries.

PMID- 23970108
TI  - Posterior bilateral supernumerary atlantoaxial facets: true or false joint?
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe a symptomatic patient with
      bilateral posterior accessory C1-C2 joints and their differences from the true
      synovial joints. SUMMARY OF BACKGROUND DATA: Accessory joints between C1-C2 are
      rarely described. Origin and functional importance of such joints is unknown.
      Moreover only gross anatomic features of such joints were discussed in the past.
      The emphasis here is to review the morphology of such joints and to differentiate
      it from normal synovial joints. METHODS: A 17-year-old male presented with
      progressive spastic ataxia precipitated by episodic transient quadriparesis
      secondary to trivial trauma. Radiology revealed bilateral posterior C1-C2
      accessory joints compressing the cervicomedullary junction. Both C1-C2 posterior
      arches were removed, excising the accessory joints. Fusion was achieved using C1
      C2 lateral mass screws and is doing well at follow-up. RESULTS: The surfaces of
      these joints were smooth. Histopatholgy showed opposing osseous surfaces with
      articular cartilage but no synovium or articular capsule. CONCLUSION: Accessory
      C1-C2 joints are possibly a result of genetic aberration giving rise to
      abnormality in segmentation of C1 sclerotome. These joints are dysmorphic and
      partially formed as evidenced by the absence of synovial membrane and capsule.
      The function of such joints remains questionable.

PMID- 23970109
TI  - Nerve root sedimentation sign for the diagnosis of lumbar spinal stenosis:
      reliability, sensitivity, and specificity.
AB  - STUDY DESIGN: Retrospective review of magnetic resonance images. OBJECTIVE:
      Examine the diagnostic accuracy, discriminative ability, and reliability of the
      sedimentation sign in a sample of patients with clinically diagnosed lumbar
      spinal stenosis (LSS), low back pain (LBP), and vascular claudication, and in
      asymptomatic controls. SUMMARY OF BACKGROUND DATA: The nerve root sedimentation
      sign (SedSign) was recently described as a new diagnostic test for LSS; however,
      the degree to which this sign is sensitive and specific in diagnosis of LSS is
      unknown. METHODS: All LSS images were obtained from subjects who had clinically
      diagnosed LSS confirmed on imaging by a spine specialist. The other images were
      obtained from people with LBP but no LSS, people with severe vascular
      claudication, and asymptomatic participants. Three blinded raters independently
      assessed the images. A positive sign was defined as the absence of nerve root
      sedimentation at the level above or below the level of maximum stenosis. RESULTS:
      Images from 148 subjects were reviewed (67 LSS, 31 LBP, 4 vascular, and 46
      asymptomatic). Intrarater reliability for the sign ranged from kappa= 0.87 to
      0.97 and inter-rater reliability from 0.62 to 0.69. Sensitivity ranged from 42%
      to 66%, and specificity ranged from 49% to 78%. Sensitivity improved to a range
      of 60% to 96% when images with only a smallest cross-sectional area of the dural
      sac less than 80 mm were included. The sign was able to differentiate (P = 0.004)
      between LSS and asymptomatic controls but not between LSS and LBP or between LSS
      and vascular claudication. CONCLUSION: The SedSign was shown to have high
      intrarater reliability and acceptable inter-rater reliability. The Sign appears
      most sensitive in defining severe LSS cases, yet may not aid in the differential
      diagnosis of LSS from LBP or vascular claudication, or add any specific
      diagnostic information beyond the traditional history, physical examination, and
      imaging studies that are standard in LSS diagnosis. LEVEL OF EVIDENCE: 4.

PMID- 23970110
TI  - Fusion risk score: evaluating baseline risk in thoracic and lumbar fusion
      surgery.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The fusion risk score (FRS)
      is introduced to assess baseline risk of spine fusion surgery preoperatively. An
      objective method of stratifying risk allows the surgeon to control risk through
      tailoring intervention and explain differences in complication profile in high
      complexity practice. SUMMARY OF BACKGROUND DATA: Research has identified an
      elevated risk of serious complications in performing spine fusion surgery in the
      elderly, yet the rate of such surgery continues to increase. A range of
      comorbidities and the surgical factors are demonstrated predictors of
      perioperative risk. METHODS: Retrospective review was made of 364 consecutive
      fusion surgical procedures in patients older than 65 years in an 18-month period.
      Logistic regression analysis was performed to identify factors predictive for the
      occurrence of perioperative events. The predictive variables were incorporated in
      a weighted fashion into the FRS scaled from 1 to 20. Patient demographics and
      comorbidities were incorporated into the FRS patient score (maximum 10) and
      surgical approach, levels, and osteotomies into the FRS procedure score (maximum
      10). RESULTS: Multivariate analysis demonstrated chronic kidney disease (odds
      ratio [OR] = 5.3, 95% confidence interval [CI]: 1.5-18.6, P = 0.008), chronic
      obstructive pulmonary disease (OR = 5.3, 95% CI: 2.0-14.2, P < 0.001), ischemic
      heart disease (OR = 4.1, 95% CI: 2.0-8.4, P < 0.001), an open anterior approach
      (OR = 3.6, 95% CI: 1.4-9.3, P = 0.010), diabetes (OR = 3.0, 95% CI: 1.4-6.4, P =
      0.004), previous spinal surgery at the same site (OR = 2.6, 95% CI: 1.3-4.9, P =
      0.005), age (OR = 1.07, 95% CI: 1.01-1.13, P = 0.019), and the number of motion
      segments fused (P = 0.049) to be predictive of perioperative events. When
      applied, the FRS was highly predictive of perioperative events, intensive care
      unit admission, operative time, blood loss, and length of stay (all P < 0.0001).
      A score over threshold 9 carries a greater than 50% risk of perioperative events.
      CONCLUSION: The FRS predicts the risk of complications after spine fusion surgery
      on the basis of patient and surgery characteristics. It also predicts the risk of
      intensive care unit admission and correlates with operative time, blood loss, and
      postoperative length of stay. By balancing the FRS procedure score to the
      individual FRS patient score, the surgeon can quantify and control perioperative
      risk.

PMID- 23970111
TI  - Cluster phenomenon of vertebral refractures after percutaneous vertebroplasty in
      a patient with glucocorticosteroid-induced osteoporosis: case report and review
      of the literature.
AB  - STUDY DESIGN: A case report and literature review. OBJECTIVE: To describe a rare
      cluster phenomenon of spontaneous vertebral refractures in a patient with
      glucocorticosteroid-induced osteoporosis (GIOP) subsequent to percutaneous
      vertebroplasty (PVP) for the management of initial vertebral compression
      fractures (VCFs). SUMMARY OF BACKGROUND DATA: PVP has become the popular strategy
      for stabilizing osteoporotic VCFs and obtaining rapid pain alleviation and
      earlier restoration of mobility in both patients with primary osteoporosis and
      patients with glucocorticosteroid-induced osteoporosis. However, current data are
      insufficient to recommend routine use of PVP for VCFs caused by GIOP as recent
      retrospective studies indicate that the risk of vertebral refractures is much
      higher in patients with GIOP than those with primary osteoporosis. METHODS: We
      reported a 63-year-old Chinese female with GIOP as well as pulmonary infection
      who underwent PVP for the management of initial VCFs, experienced the cluster
      phenomenon of spontaneous vertebral refractures. RESULTS: Within a 4-month
      period, she underwent a total of 6 PVP operations with 13 cement-augmented
      vertebral bodies from T5-L5. Eleven refractures after the initial PVP procedures
      included 3 remote-level fractures, 4 adjacent-level fractures, 1 pincher body
      fracture, and 3 fractures in previously augmented bodies. The average interval
      between each PVP operation was 23.6 days. CONCLUSION: The use of PVP as a
      therapeutic alternative for the treatment of VCFs in patients with GIOP is still
      controversial. As seen in our case, even when the management decisions were made
      in consideration of the patient's pulmonary infection, the outcome was disastrous
      with the cluster phenomenon of vertebral refractures. Current findings suggest a
      compelling need for high-quality studies investigating cement augmentation
      procedures in patients with VCF with GIOP.

PMID- 23970112
TI  - Twenty-five years with the biopsychosocial model of low back pain-is it time to
      celebrate? A report from the twelfth international forum for primary care
      research on low back pain.
AB  - STUDY DESIGN: An integrated review of current knowledge about the biopsychosocial
      model of back pain for understanding etiology, prognosis, and interventions, as
      presented at the plenary sessions of the XII International Forum on LBP Research
      in Primary Care (Denmark; October 17-19, 2012). OBJECTIVE: To evaluate the
      utility of the model in reference to rising rates of back pain-related
      disability, by identifying (a) the most promising avenues for future research in
      biological, psychological, and social approaches, (b) promising combinations of
      all 3 approaches, and (c) obstacles to effective implementation of
      biopsychosocial-based research and clinical practice. SUMMARY OF BACKGROUND DATA:
      The biopsychosocial model of back pain has become a dominant model in the
      conceptualization of the etiology and prognosis of back pain, and has led to the
      development and testing of many interventions. Despite this back pain remains a
      leading source of disability worldwide. METHODS: The review is a synthesis based
      on the plenary sessions and discussions at the XII International Forum on LBP
      Research in Primary Care. The presentations included evidence-based reviews of
      the current state of knowledge in each of the 3 areas (biological, psychological,
      and social), identification of obstacles to effective implementation and missed
      opportunities, and identification of the most promising paths for future
      research. RESULTS: Although there is good evidence for the role of biological,
      psychological, and social factors in the etiology and prognosis of back pain,
      synthesis of the 3 in research and clinical practice has been suboptimal.
      CONCLUSION: The utility of the biopsychosocial framework cannot be fully assessed
      until we truly adopt and apply it in research and clinical practice. LEVEL OF
      EVIDENCE: N/A.

PMID- 23970113
TI  - Fibrous dysplasia of the mobile spine: report of 8 cases and review of the
      literature.
AB  - STUDY DESIGN: Eight cases of fibrous dysplasia (FD) of the mobile spine treated
      surgically at the same center were retrospectively reviewed. OBJECTIVE: The study
      focuses on the issues concerning the diagnosis of FD and the outcome of
      conventional surgical techniques (resection or curettage) and vertebroplasty in
      the treatment of spinal FD lesions. SUMMARY OF BACKGROUND DATA: Surgical excision
      or curettage is considered the standard treatment of spinal FD, whereas
      vertebroplasty is also performed occasionally. METHODS: Between January 2005 and
      October 2010, 8 consecutive patients with spinal FD underwent conventional
      surgery (6 cases) or combined with vertebroplasty (2 cases). Before surgery, 4
      patients underwent percutaneous computed tomography-guided biopsy, whereas 3 had
      incorrect histopathological diagnosis. In each of the 8 cases, the final
      pathological diagnosis was established after their open surgery. RESULTS: Pain
      relief was observed postoperatively in all patients. Three patients with
      neurological impairment became symptom-free after surgery. No cement
      extravasation was observed. Screw loosening and allograft resorption were
      observed in 1 case each. Signs of radiological improvement (filling of lytic
      lesions or thickening of the bone cortex surrounding the lesions) were not
      detected in any case. CONCLUSION: The radiological features of spinal FD may be
      atypical. The rate of correct preoperative pathological diagnosis by computed
      tomography-guided biopsy was low for patients with suspected spinal FD.
      Vertebroplasty is probably a valuable therapeutic option for spinal FD with
      pathological fractures. Limited decompression and stability with vertebroplasty
      might be recommended for patients with neurological deficits.

PMID- 23970114
TI  - Acute effects of different inspiratory resistive loading on heart rate
      variability in healthy elderly patients.
AB  - BACKGROUND: The cardiovascular system is noticeably affected by respiration.
      However, whether different inspiratory resistive loading intensities can
      influence autonomic heart rate (HR) modulation remains unclear. OBJECTIVE: The
      objective was to investigate HR modulation at three different inspiratory
      resistive loading intensities in healthy elderly men. METHOD: This was a
      prospective, randomized, double-blind study that evaluated 25 healthy elderly
      men. Cardiac autonomic modulation was assessed using heart rate variability (HRV)
      indices. All of the volunteers underwent maximal inspiratory pressure (MIP)
      measurements according to standardized pulmonary function measurements. Three
      randomly-applied inspiratory resistive loading (30, 60 and 80% of MIP)
      intensities were then applied using an inspiratory resistance device
      (POWERbreathe, Southam, UK), during which the volunteers were asked to inhale for
      2 seconds and exhale for 3 seconds and complete 12 breaths per minute. Each
      effort level was performed for 4 minutes, and HR and the distance between 2
      subsequent R waves of electrocardiogram (R-R intervals) were collected at rest
      and at each intensity for further HRV analysis. RESULTS: The parasympathetic HRV
      (rMSSD, SD1 and HF) indices demonstrated lower values at 80% (rMSSD: 19+/-2 ms,
      SD1: 13+/-2 ms and HF: 228+/-61 ms2) than at 30% MIP (rMSSD: 25+/-3 ms, SD1: 18+/
      2 ms and HF: 447+/-95 ms2; p<0.05). CONCLUSIONS: Lower inspiratory resistive
      loading intensities promoted a marked and positive improvement of parasympathetic
      sinus node modulation.

PMID- 23970115
TI  - Influence of sarcopenia and functionality indicators on the frailty profile of
      community-dwelling elderly subjects: a cross-sectional study.
AB  - BACKGROUND: Frailty and sarcopenia are frequent conditions in the elderly and are
      related to inactivity and functionality. However, little is known about the
      influence of the sarcopenia indicators on the frailty profile or their functional
      implications. OBJECTIVE: To evaluate whether the indirect indicators of
      sarcopenia and functionality influence the frailty profile in elderly subjects.
      METHOD: This was a cross-sectional study with 53 elderly subjects recruited by an
      active search in a secondary health care service. The indirect indicators of
      sarcopenia were body mass index (BMI), gait speed, Mini-Nutritional Assessment
      (MNA), Human Activity Profile (HAP), and handgrip strength. Frailty was
      characterized according to Fried's Frailty Phenotype. Functional capacity was
      assessed according to the Short Physical Performance Battery (SPPB). Physical
      activity level was assessed by HAP. Data were analyzed by analysis of variance
      (ANOVA) and multiple regression. RESULTS: Overall, 75.5% of the subjects were
      women, with a mean age of 76.72 (+/-5.89) years; 15.1% were frail and 54.7% pre
      frail; and the level of physical activity was the most prevalent indicator of
      sarcopenia. Significant differences (p<0.05) were observed in both the physical
      activity level and gait speed between the non-frail and pre-frail groups and
      between the non-frail and frail groups. In addition, some sarcopenia indicators
      were associated with functional capacity and geriatric depression score.
      CONCLUSION: The level of physical activity and gait speed appeared to be the most
      relevant factors in the development of frailty in the study sample, which may
      have functional implications.

PMID- 23970116
TI  - Effects of low-intensity pulsed ultrasound on injured skeletal muscle.
AB  - BACKGROUND: Low-intensity pulsed ultrasound (LIPUS) has been shown to stimulate
      tissue metabolism and accelerate muscle healing. However, the optimal parameters
      in the use of LIPUS are still not clear. OBJECTIVE: The aim of this study was to
      analyze the effects of LIPUS on muscle healing in rats subjected to a cryolesion.
      METHOD: Twenty rats were divided into the following groups: an injured control
      group (CG) and an injured treated group (TG). Both groups were divided into 2 sub
      groups (n=5 each) that were sacrificed 7 and 13 days post-surgery. Treatments
      were started 24 hours after the surgical procedure and consisted of 3 or 6
      sessions. After euthanasia, the muscles were submitted to standard histological
      procedures. RESULTS: Qualitative analyses were based on morphological assessments
      of the muscle. The histopathological analysis on day 7 revealed that the muscles
      in the CG and the TG presented an intense inflammatory infiltrate, a large
      necrotic area and a disorganized tissue structure. After 13 days, both the CG and
      the TG had granulation tissue and newly formed fibers. The TG presented a more
      organized tissue structure. The quantitative analysis of collagen indicated
      similar findings among the groups, although the qualitative analysis revealed a
      better organization of collagen fibers in the TG at 13 days. The
      immunohistochemical analysis indicated that, at both time points, the expression
      of cyclooxygenase-2 was upregulated in the TG compared to the CG. CONCLUSIONS:
      LIPUS used as a treatment for muscle injury induced a more organized tissue
      structure at the site of the injury and stimulated the expression of COX-2 and
      the formation of new muscle fibers.

PMID- 23970117
TI  - Human biomonitoring issues related to lead exposure.
AB  - Lead as a toxic environmental metal has been an issue of concern for 30-40 years.
      Even though the exposures experienced by the general public have been
      significantly reduced, so have the acceptable blood lead concentrations assessed
      to safeguard health (specifically of children). The impact of these concurrent
      changes are reviewed and discussed in terms of the following: blood lead as the
      primary biomarker of exposure; pertinent toxicokinetic issues including
      modelling; legacy and newer sources of this toxic metal; improvements in lead
      quantification techniques and its characterization (chemical forms) in exposure
      media; and in vivo markers of lead sources. It is concluded that the progress in
      the quantification of lead and its characterization in exposure media have
      supported the efforts to identify statistical associations of lead in blood and
      tissues with adverse health outcomes, and have guided strategies to reduce human
      exposure (especially for children). To clarify the role of lead as a causative
      factor in disease, greater research efforts in biomarkers of effect and
      susceptibility seem timely. 

PMID- 23970119
TI  - Self-assembly mechanism of thiol, dithiol, dithiocarboxylic acid, disulfide and
      diselenide on gold: an electrochemical impedance study.
AB  - The self-assembly mechanism of normal aliphatic thiol (RSH), disulfide (RSSR),
      diselenide (RSeSeR), dithiol (R(SH)2) and dithiocarboxylic acid (RS2H) onto a
      gold surface was studied in real time by electrochemical impedance spectroscopy
      (EIS). The different stages of adsorption could be clearly followed from the
      interfacial capacitance variation. An initial very fast adsorption, varying from
      a few seconds to several minutes depending on concentration, is the major
      adsorption step. This fast step is followed by long-term additional adsorption
      and self-assembled monolayer (SAM) consolidation. However, an intermediate step,
      probably due to transformation from the initial physisorbed state to the self
      assembled state, could be identified with RSH and R(SH)2. An intermediate
      rearrangement of RS2H molecules after their initial diffusion controlled Langmuir
      (DCL) adsorption through the thiol functional group was also recognized. Initial
      adsorption of RSH and R(SH)2 followed either purely diffusion controlled or DCL
      kinetics for a very short time. Their continuing fast adsorption followed DCL
      kinetics. The fast adsorption step of RSSR and RSeSeR also followed the same
      mechanism. The findings made with EIS on the SAM organization were analyzed by
      polarization modulation infrared reflection absorption spectroscopy (PM-IRRAS).
      The R(SH)2 based SAMs had comparatively poor organization. 

PMID- 23970118
TI  - VHL-dependent regulation of a beta-dystroglycan glycoform and glycogene
      expression in renal cancer.
AB  - Identification of novel biomarkers and targets in renal cell carcinoma (RCC)
      remains a priority and one cellular compartment that is a rich potential source
      of such molecules is the plasma membrane. A shotgun proteomic analysis of cell
      surface proteins enriched by cell surface biotinylation and avidin affinity
      chromatography was explored using the UMRC2- renal cancer cell line, which lacks
      von Hippel-Lindau (VHL) tumour suppressor gene function, to determine whether
      proteins of interest could be detected. Of the 814 proteins identified ~22% were
      plasma membrane or membrane-associated, including several with known associations
      with cancer. This included beta-dystroglycan, the transmembrane subunit of the
      DAG1 gene product. VHL-dependent changes in the form of beta-dystroglycan were
      detected in UMRC2-/+VHL transfectants. Deglycosylation experiments showed that
      this was due to differential sialylation. Analysis of normal kidney cortex and
      conventional RCC tissues showed that a similar change also occurred in vivo.
      Investigation of the expression of genes involved in glycosylation in UMRC2-/+VHL
      cells using a focussed microarray highlighted a number of enzymes involved in
      sialylation; upregulation of bifunctional UDP-N-acetylglucosamine 2-epimerase/N
      acetylmannosamine kinase (GNE) was validated in UMRC2- cells compared with their
      +VHL counterparts and also found in conventional RCC tissue. These results
      implicate VHL in the regulation of glycosylation and raise interesting questions
      regarding the extent and importance of such changes in RCC. 

PMID- 23970120
TI  - Facility size, race and ethnicity, and mortality for in-center hemodialysis.
AB  - The association between dialysis facility size and mortality for patients
      undergoing hemodialysis remains largely unclear, and whether the relationship
      differs by race and ethnicity or among high-risk subgroups is not known. Using
      data from the USRDS, we analyzed mortality rates in 385,074 incident patients
      ages >= 18 years who received in-center hemodialysis at 4633 dialysis facilities
      between 2003 and 2009. Facilities were categorized by the number of hemodialysis
      stations (1-5, 6-10, 11-15, 16-20, 21-25, 26-30, 31-35, 36-45, 46-60, and >= 61
      stations). We found significantly higher mortality associated with facilities
      comprising <= 15 stations, and within this group, mortality increased as the
      number of stations decreased. The association with increased mortality was weaker
      for facilities with 16-30 stations, but >30 stations offered no additional
      survival benefit. The association between increased mortality and facilities with
      <= 15 stations was stronger for racial minorities and patients with diabetes or
      cardiovascular diseases. After adjustments, blacks had a 78% greater 1-year
      mortality risk in facilities with one to five stations, whereas whites had only a
      26% greater risk. Notably, other patient-related events remained comparable
      across the categories assessed. In summary, these data suggest that hemodialysis
      care at small facilities associates with a significant increase in mortality that
      is only partially explained by measured patient case mix, other well defined
      facility characteristics, and geographic region. Future studies should
      investigate differences in processes of care and practices among hemodialysis
      facilities of different sizes.

PMID- 23970122
TI  - The upfront risks of vascular access complications.

PMID- 23970121
TI  - ABIN1 dysfunction as a genetic basis for lupus nephritis.
AB  - The genetic factors underlying the pathogenesis of lupus nephritis associated
      with systemic lupus erythematosus are largely unknown, although animal studies
      indicate that nuclear factor (NF)-kappaB is involved. We reported previously that
      a knockin mouse expressing an inactive form of ABIN1 (ABIN1[D485N]) develops
      lupus-like autoimmune disease and demonstrates enhanced activation of NF-kappaB
      and mitogen-activated protein kinases in immune cells after toll-like receptor
      stimulation. In the current study, we show that ABIN1[D485N] mice develop
      progressive GN similar to class III and IV lupus nephritis in humans. To
      investigate the clinical relevance of ABIN1 dysfunction, we genotyped five single
      nucleotide polymorphisms in the gene encoding ABIN1, TNIP1, in samples from
      European-American, African American, Asian, Gullah, and Hispanic participants in
      the Large Lupus Association Study 2. Comparing cases of systemic lupus
      erythematosus with nephritis and cases of systemic lupus erythematosus without
      nephritis revealed strong associations with lupus nephritis at rs7708392 in
      European Americans and rs4958881 in African Americans. Comparing cases of
      systemic lupus erythematosus with nephritis and healthy controls revealed a
      stronger association at rs7708392 in European Americans but not at rs4958881 in
      African Americans. Our data suggest that variants in the TNIP1 gene are
      associated with the risk for lupus nephritis and could be mechanistically
      involved in disease development via aberrant regulation of NF-kappaB and mitogen
      activated protein kinase activity. 

PMID- 23970123
TI  - Albumin is recycled from the primary urine by tubular transcytosis.
AB  - Under physiologic conditions, significant amounts of plasma protein pass the
      renal filter and are reabsorbed by proximal tubular cells, but it is not clear
      whether the endocytosed protein, particularly albumin, is degraded in lysosomes
      or returned to the circulatory system intact. To resolve this question, a
      transgenic mouse with podocyte-specific expression of doxycycline-inducible
      tagged murine albumin was developed. To assess potential glomerular
      backfiltration, two types of albumin with different charges were expressed. On
      administration of doxycycline, podocytes expressed either of the two types of
      transgenic albumin, which were secreted into the primary filtrate and reabsorbed
      by proximal tubular cells, resulting in serum accumulation. Renal transplantation
      experiments confirmed that extrarenal transcription of transgenic albumin was
      unlikely to account for these results. Genetic deletion of the neonatal Fc
      receptor (FcRn), which rescues albumin and IgG from lysosomal degradation,
      abolished transcytosis of both types of transgenic albumin and IgG in proximal
      tubular cells. In summary, we provide evidence of a transcytosis within the
      kidney tubular system that protects albumin and IgG from lysosomal degradation,
      allowing these proteins to be recycled intact. 

PMID- 23970124
TI  - NADPH oxidases, reactive oxygen species, and the kidney: friend and foe.
AB  - Reactive oxygen species (ROS) play an important role in normal cellular
      physiology. They regulate different biologic processes such as cell defense,
      hormone synthesis and signaling, activation of G protein-coupled receptors, and
      ion channels and kinases/phosphatases. ROS are also important regulators of
      transcription factors and gene expression. On the other hand, in pathologic
      conditions, a surplus of ROS in tissue results in oxidative stress with various
      injurious consequences such as inflammation and fibrosis. NADPH oxidases are one
      of the many sources of ROS in biologic systems, and there are seven isoforms
      (Nox1-5, Duox1, Duox2). Nox4 is the predominant form in the kidney, although Nox2
      is also expressed. Nox4 has been implicated in the basal production of ROS in the
      kidney and in pathologic conditions such as diabetic nephropathy and CKD;
      upregulation of Nox4 may be important in renal oxidative stress and kidney
      injury. Although there is growing evidence indicating the involvement of NADPH
      oxidase in renal pathology, there is a paucity of information on the role of
      NADPH oxidase in the regulation of normal renal function. Here we provide an
      update on the role of NADPH oxidases and ROS in renal physiology and pathology. 

PMID- 23970126
TI  - Design of meso-TiO2@MnO(x)-CeO(x)/CNTs with a core-shell structure as DeNO(x)
      catalysts: promotion of activity, stability and SO2-tolerance.
AB  - Developing low-temperature deNOx catalysts with high catalytic activity, SO2
      tolerance and stability is highly desirable but remains challenging. Herein, by
      coating the mesoporous TiO2 layers on carbon nanotubes (CNTs)-supported MnOx and
      CeOx nanoparticles (NPs), we obtained a core-shell structural deNOx catalyst with
      high catalytic activity, good SO2-tolerance and enhanced stability. Transmission
      electron microscopy, X-ray diffraction, N2 sorption, X-ray photoelectron
      spectroscopy, H2 temperature-programmed reduction and NH3 temperature-programmed
      desorption have been used to elucidate the structure and surface properties of
      the obtained catalysts. Both the specific surface area and chemisorbed oxygen
      species are enhanced by the coating of meso-TiO2 sheaths. The meso-TiO2 sheaths
      not only enhance the acid strength but also raise acid amounts. Moreover, there
      is a strong interaction among the manganese oxide, cerium oxide and meso-TiO2
      sheaths. Based on these favorable properties, the meso-TiO2 coated catalyst
      exhibits a higher activity and more extensive operating-temperature window,
      compared to the uncoated catalyst. In addition, the meso-TiO2 sheaths can serve
      as an effective barrier to prevent the aggregation of metal oxide NPs during
      stability testing. As a result, the meso-TiO2 overcoated catalyst exhibits a much
      better stability than the uncoated one. More importantly, the meso-TiO2 sheaths
      can not only prevent the generation of ammonium sulfate species from blocking the
      active sites but also inhibit the formation of manganese sulfate, resulting in a
      higher SO2-tolerance. These results indicate that the design of a core-shell
      structure is effective to promote the performance of deNOx catalysts. 

PMID- 23970125
TI  - Tubular von Hippel-Lindau knockout protects against rhabdomyolysis-induced AKI.
AB  - Renal hypoxia occurs in AKI of various etiologies, but adaptation to hypoxia,
      mediated by hypoxia-inducible factor (HIF), is incomplete in these conditions.
      Preconditional HIF activation protects against renal ischemia-reperfusion injury,
      yet the mechanisms involved are largely unknown, and HIF-mediated renoprotection
      has not been examined in other causes of AKI. Here, we show that selective
      activation of HIF in renal tubules, through Pax8-rtTA-based inducible knockout of
      von Hippel-Lindau protein (VHL-KO), protects from rhabdomyolysis-induced AKI. In
      this model, HIF activation correlated inversely with tubular injury.
      Specifically, VHL deletion attenuated the increased levels of serum
      creatinine/urea, caspase-3 protein, and tubular necrosis induced by
      rhabdomyolysis in wild-type mice. Moreover, HIF activation in nephron segments at
      risk for injury occurred only in VHL-KO animals. At day 1 after rhabdomyolysis,
      when tubular injury may be reversible, the HIF-mediated renoprotection in VHL-KO
      mice was associated with activated glycolysis, cellular glucose uptake and
      utilization, autophagy, vasodilation, and proton removal, as demonstrated by
      quantitative PCR, pathway enrichment analysis, and immunohistochemistry. In
      conclusion, a HIF-mediated shift toward improved energy supply may protect
      against acute tubular injury in various forms of AKI. 

PMID- 23970127
TI  - Assessment of printed patient-educational materials for chronic kidney disease.
AB  - BACKGROUND: Awareness of chronic kidney disease (CKD) is suboptimal among
      patients with CKD, perhaps due to poor readability of patient education materials
      (PEMs). We reviewed the suitability and readability of common PEMs that focused
      on 5 content areas: basics of CKD, risk factors for CKD development, risk factors
      for CKD progression, complications of CKD and self-management strategies to
      improve kidney health. METHODS: Three reviewers (nephrologist, primary care
      physician, patient) used the Suitability Assessment of Materials to rate PEMs on
      message content/stimulation of learning, typography, visuals and layout and
      determined literacy level. Mean ratings were calculated for each PEM by content
      area and overall (superior = 70-100; adequate = 40-69; inadequate = <40). Linear
      regression was used to determine the impact of literacy level on mean rating.
      RESULTS: We reviewed 69 PEMs from 19 organizations, divided into 113 content area
      sections. Most (79%) PEM sections were 'adequate' (mean rating, 58.3%). Inclusion
      of patient-centered content and opportunities for patient interaction were
      associated with 'superior' ratings. Mean ratings (SD) were similar across content
      areas: basics of CKD, 58.9% (9.1); risk factors for CKD development, 57.0%
      (12.3); risk factors for CKD progression, 58.5% (12.0); CKD complications, 62.3%
      (15.7), and self-management strategies, 62.2% (12.3). <=6th grade literacy level
      (vs. >6th grade) was associated with an 11.7 point higher mean rating.
      CONCLUSION: Most PEMs for kidney disease were adequate. Outstanding PEMs shared
      characteristics of patient centeredness, a low literacy level, and patient
      interaction. Providers should be aware of strengths and limitations of PEMs when
      educating their patients about CKD.

PMID- 23970128
TI  - Sundays and mortality in patients with AKI.
AB  - BACKGROUND AND OBJECTIVES: Initiation of dialysis on Sunday is limited by
      constraints that do not exist on other days of the week, which may lead to
      triaging of dialysis therapy. The study hypothesis was that patients with AKI on
      a Sunday would sustain higher mortality rates. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Study participants (n=4970) were part of the retrospective
      University of Pennsylvania Health AKI cohort, which is composed of patients with
      severe inpatient AKI (characterized by a doubling of admission creatinine) who
      were hospitalized from January 1, 2004, to August 31, 2010. Patient-days
      (n=15,995) were included if the patient had AKI severity of Acute Kidney Injury
      Network (AKIN) stage 2 or greater and had not yet begun receiving dialysis. The
      association of day of the week and inpatient mortality was assessed with logistic
      regression of data updated daily, using robust variance estimators. RESULTS: The
      rate (95% confidence interval [CI]) of initiation of dialysis on Sunday was 2.5
      (1.8 to 3.1) per 100 patient-days, compared with 3.8 (3.5 to 4.1) per 100 patient
      days on other days of the week (P=0.001). Inpatient mortality (95% CI) among
      patients with severe AKI present on a Sunday was 30% (28% to 32%), compared with
      31% (31% to 32%) on other days of the week (P=0.08). Inpatient mortality among
      patients who initiated dialysis on Sunday was 65% (52% to 79%), compared with 65%
      (61% to 70%) among those who initiated dialysis from Tuesday through Saturday
      (P=0.79). Patients who initiated dialysis on Monday had a lower mortality than
      those who initiated it on another day of the week (52% [40% to 64%] versus 65%
      [61% to 70%]; P=0.03). CONCLUSIONS: Despite a lower frequency of dialysis,
      patients with severe AKI on Sunday have mortality similar to that of patients
      with severe AKI on other days of the week.

PMID- 23970129
TI  - Strategies for postmarketing surveillance of drugs and devices in patients with
      ESRD undergoing dialysis.
AB  - The lack of evidence on the effectiveness and safety of interventions in chronic
      dialysis patients has been a subject of continuing criticism. New technologies
      are often introduced into the market without having specifically studied or even
      included patients with advanced kidney disease. Therefore, the need to generate
      valid effectiveness and safety data in this vulnerable subpopulation is of utmost
      importance. The US Food and Drug Administration has recently placed an increased
      focus on safety surveillance, and sponsors must now meet this additional
      postmarketing commitment. In patients with ESRD, the unique data collection
      environment in the United States allows for creative and efficient study designs
      to meet the needs of patients, providers, and sponsors. The purpose of this
      manuscript is to review the methodological and practical aspects of the different
      options for postmarketing study design in this field, with critical appraisal of
      their advantages and disadvantages. 

PMID- 23970130
TI  - Carbamylation of serum albumin and erythropoietin resistance in end stage kidney
      disease.
AB  - BACKGROUND AND OBJECTIVES: The mechanisms underlying erythropoietin resistance
      are not fully understood. Carbamylation is a post-translational protein
      modification that can alter the function of proteins, such as erythropoietin. The
      hypothesis of this study is that carbamylation burden is independently associated
      with erythropoietin resistance. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In
      a nonconcurrent prospective cohort study of incident hemodialysis patients in the
      United States, carbamylated albumin, a surrogate of overall carbamylation burden,
      in 158 individuals at day 90 of dialysis initiation and erythropoietin resistance
      index (defined as average weekly erythropoietin dose [U] per kg body weight per
      hemoglobin [g/dl]) over the subsequent 90 days were measured. Linear regression
      was used to describe the relationship between carbamylated albumin and
      erythropoietin resistance index. Logistic regression characterized the
      relationship between erythropoietin resistance index, 1-year mortality, and
      carbamylation. RESULTS: The median percent carbamylated albumin was 0.77%
      (interquartile range=0.58%-0.93%). Median erythropoietin resistance index was
      18.7 units/kg per gram per deciliter (interquartile range=8.1-35.6 units/kg per
      gram per deciliter). Multivariable adjusted analysis showed that the highest
      quartile of carbamylated albumin was associated with a 72% higher erythropoietin
      resistance index compared with the lowest carbamylation quartile (P=0.01).
      Increasing erythropoietin resistance index was associated with a higher risk of
      death (odds ratio per unit increase in log-erythropoietin resistance index, 1.69;
      95% confidence interval, 1.06 to 2.70). However, the association between
      erythropoietin resistance index and mortality was no longer statistically
      significant when carbamylation was included in the analysis (odds ratio, 1.44;
      95% confidence interval, 0.87 to 2.37), with carbamylation showing the dominant
      association with death (odds ratio for high versus low carbamylation quartile,
      4.53; 95% confidence interval, 1.20 to 17.10). CONCLUSION: Carbamylation was
      associated with higher erythropoietin resistance index in incident dialysis
      patients and a better predictor of mortality than erythropoietin resistance
      index.

PMID- 23970131
TI  - Effects of frequent hemodialysis on ventricular volumes and left ventricular
      remodeling.
AB  - BACKGROUND AND OBJECTIVES: Higher left ventricular volume is associated with
      death in patients with ESRD. This work investigated the effects of frequent
      hemodialysis on ventricular volumes and left ventricular remodeling. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: The Frequent Hemodialysis Network daily
      trial randomized 245 patients to 12 months of six times per week versus three
      times per week in-center hemodialysis; the Frequent Hemodialysis Network
      nocturnal trial randomized 87 patients to 12 months of six times per week
      nocturnal hemodialysis versus three times per week predominantly home-based
      hemodialysis. Left and right ventricular end systolic and diastolic volumes, left
      ventricular mass, and ejection fraction at baseline and end of the study were
      ascertained by cardiac magnetic resonance imaging. The ratio of left ventricular
      mass/left ventricular end diastolic volume was used as a surrogate marker of left
      ventricular remodeling. In each trial, the effect of frequent dialysis on left or
      right ventricular end diastolic volume was tested between predefined subgroups.
      RESULTS: In the daily trial, frequent hemodialysis resulted in significant
      reductions in left ventricular end diastolic volume (-11.0% [95% confidence
      interval, -16.1% to -5.5%]), left ventricular end systolic volume (-14.8% [-22.7%
      to -6.2%]), right ventricular end diastolic volume (-11.6% [-19.0% to -3.6%]),
      and a trend for right ventricular end systolic volume (-11.3% [-21.4% to 0.1%])
      compared with conventional therapy. The magnitude of reduction in left and right
      ventricular end diastolic volumes with frequent hemodialysis was accentuated
      among patients with residual urine output<100 ml/d (P value [interaction]=0.02).
      In the nocturnal trial, there were no significant changes in left or right
      ventricular volumes. The frequent dialysis interventions had no substantial
      effect on the ratio of left ventricular mass/left ventricular end diastolic
      volume in either trial. CONCLUSIONS: Frequent in-center hemodialysis reduces left
      and right ventricular end systolic and diastolic ventricular volumes as well as
      left ventricular mass, but it does not affect left ventricular remodeling.

PMID- 23970132
TI  - Dancing around elephants.

PMID- 23970133
TI  - Dying on dialysis: the case for a dignified withdrawal.
AB  - Acceleration of comorbid illness in patients undergoing long-term maintenance
      hemodialysis may be manifested by clinical deterioration that is subtle and not
      immediately life-threatening. Nonetheless, it is emotionally debilitating for
      patients and families in addition to being medically and ethically challenging
      for treating nephrologists. A marked decline in clinical status warrants review
      of the balance of benefits to burdens dialysis is providing to a given patient
      and should trigger conversation about the option of withdrawal using an
      individualized patient-centered, rather than disease-oriented, approach. This
      paper presents a rationale for and an objective approach to initiating and
      managing dialysis withdrawal for patients who wish to withdraw because of
      unsatisfactory quality of life and those (many with significant cognitive
      impairment) for whom withdrawal is deemed appropriate because the burdens of
      continuing treatment substantially outweigh the benefits. 

PMID- 23970134
TI  - A patient with CKD and poor nutritional status.
AB  - Protein energy wasting is common in patients with CKD and ESRD and is associated
      with adverse clinical outcomes, such as increased rates of hospitalization and
      death, in these patients. A multitude of factors can affect the nutritional and
      metabolic status of patients with CKD, including decreased dietary nutrient
      intake, catabolic effects of renal replacement therapy, systemic inflammation,
      metabolic and hormonal derangements, and comorbid conditions (such as diabetes
      and depression). Unique aspects of CKD also confound reliable assessment of
      nutritional status, further complicating management of this comorbid condition.
      In patients in whom preventive measures and oral dietary intake from regular
      meals cannot help them maintain adequate nutritional status, nutritional
      supplementation, administered orally, enterally, or parenterally, is effective in
      replenishing protein and energy stores. The advantages of oral nutritional
      supplements include proven efficacy, safety, and compliance. Anabolic steroids
      and exercise, with nutritional supplementation or alone, improve protein stores
      and represent potential additional approaches for the treatment of PEW. There are
      several emerging novel therapies, such as appetite stimulants, anti-inflammatory
      interventions, and anabolic agents. 

PMID- 23970135
TI  - Neighborhood socioeconomic status and barriers to peritoneal dialysis: a mixed
      methods study.
AB  - BACKGROUND AND OBJECTIVES: The objective of this study was to evaluate the
      association between neighborhood socioeconomic status and barriers to peritoneal
      dialysis eligibility and choice. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      This study was a mixed methods parallel design study using quantitative and
      qualitative data from a prospective clinical database of ESRD patients. The
      eligibility and choice cohorts were assembled from consecutive incident chronic
      dialysis patients entering one of five renal programs in the province of Ontario,
      Canada, between January 1, 2004 and December 31, 2010. Socioeconomic status was
      measured as median household income and percentage of residents with at least a
      high school education using Statistics Canada dissemination area-level data.
      Multivariable models described the relationship between socioeconomic status and
      likelihood of peritoneal dialysis eligibility and choice. Barriers to peritoneal
      dialysis eligibility and choice were classified into qualitative categories using
      the thematic constant comparative approach. RESULTS: The peritoneal dialysis
      eligibility and choice cohorts had 1314 and 857 patients, respectively; 65% of
      patients were deemed eligible for peritoneal dialysis, and 46% of eligible
      patients chose peritoneal dialysis. Socioeconomic status was not a significant
      predictor of peritoneal dialysis eligibility or choice in this study. Qualitative
      analyses identified 16 barriers to peritoneal dialysis choice. Patients in lower-
      versus higher-income Statistics Canada dissemination areas cited built
      environment or space barriers to peritoneal dialysis (4.6% versus 2.7%) and
      family or social support barriers (8.3% versus 3.5%) more frequently.
      CONCLUSIONS: Peritoneal dialysis eligibility and choice were not associated with
      socioeconomic status. However, socioeconomic status may influence specific
      barriers to peritoneal dialysis choice. Additional studies to determine the
      effect of targeting interventions to specific barriers to peritoneal dialysis
      choice in low socioeconomic status patients on peritoneal dialysis use are
      needed.

PMID- 23970136
TI  - Effects of exercise and lifestyle intervention on cardiovascular function in CKD.
AB  - BACKGROUND AND OBJECTIVES: CKD is associated with poor cardiorespiratory fitness
      (CRF). This predefined substudy determined the effect of exercise training and
      lifestyle intervention on CRF and explored the effect on cardiovascular risk
      factors and cardiac and vascular function. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Between February 2008 and March 2010, 90 patients with stage 3-4
      CKD were screened with an exercise stress echocardiogram before enrollment.
      Patients (n=83) were randomized to standard care (control) or lifestyle
      intervention. The lifestyle intervention included multidisciplinary care (CKD
      clinic), a lifestyle program, and aerobic and resistance exercise training for 12
      months. CRF (peak Vo2), left ventricular function, arterial stiffness,
      anthropometric, and biochemical data were collected at baseline and 12 months.
      RESULTS: Ten percent of randomized patients had subclinical myocardial ischemia
      at screening and completed the study without incident. There was no baseline
      difference among 72 patients who completed follow-up (36 in the lifestyle
      intervention group and 36 in the control group). The intervention increased peak
      Vo2 (2.8+/-0.7 ml/kg per minute versus -0.3+/-0.9 ml/kg per minute; P=0.004).
      There was small weight loss (-1.8+/-4.2 kg versus 0.7+/-3.7 kg; P=0.02) but no
      change in BP or lipids. Diastolic function improved (increased e' of 0.75+/-1.16
      cm/s versus -0.47+/-1.0 cm/s; P=0.001) but systolic function was well preserved
      and did not change. The change in arterial elastance was attenuated (0.11+/-0.76
      mmHg/ml versus 0.76+/-0.96 mmHg/ml; P=0.01). Delta peak Vo2 was associated with
      group allocation and improved body composition. CONCLUSIONS: Exercise training
      and lifestyle intervention in patients with CKD produces improvements in CRF,
      body composition, and diastolic function.

PMID- 23970137
TI  - Acral purpura as leading clinical manifestation of dermatitis herpetiformis:
      report of two adult cases with a review of the literature.
AB  - Dermatitis herpetiformis (DH) is an autoimmune disease that clinically manifests
      as pruritic vesicles and papules. The diagnosis of DH is often challenging
      because of its wide spectrum of clinical presentations. We here report 2 patients
      with DH in whom finger petechiae represented the initial and leading
      manifestation of the disease, and the confirmed diagnosis critically relied on
      immunopathological studies. Therefore, besides the classic causes, clinicians
      should also consider DH in the differential diagnosis of acral purpura, even in
      patients only presenting with discrete acral petechial lesions. We also review
      the recent literature regarding the rare cases of petechiae in adult DH patients.

PMID- 23970138
TI  - Enhancement of baicalin by hexamethylene bisacetamide on the induction of
      apoptosis contributes to simultaneous activation of the intrinsic and extrinsic
      apoptotic pathways in human leukemia cells.
AB  - Hexamethylene bisacetamide (HMBA) and natural flavanoid baicalin both exert
      potent antileukemic activity. However, there is currently no data on the anti
      leukemic effects of baicalin in combination with HMBA. In the present study, we
      demonstrated that the combination of baicalin and HMBA synergistically inhibited
      the proliferation of acute myeloid leukemia (AML) cell lines. In addition, a
      slight G0/G1 phase arrest and significant apoptosis were observed. The
      combination treatment triggered apoptosis through the intrinsic pathway, which
      involved loss of MMP, decreased Bcl-2/Bax ratio and Bcl-XL/Bax ratio, caspase-9
      activation, as well as through the extrinsic pathway mediated by Fas and caspase
      8 activation. On the other hand, combination of baicalin and HMBA showed little
      toxic effect on peripheral blood mononuclear cells from healthy volunteers. Our
      results raise the possibility that the novel combination of baicalin and HMBA may
      be a promising regimen for the treatment of AML. 

PMID- 23970139
TI  - Antimicrobial activity of alexidine alone and associated with N-acetylcysteine
      against Enterococcus faecalis biofilm.
AB  - The purpose of this study was to assess the efficacy of alexidine (ALX), alone
      and combined with N-acetylcysteine (NAC), in eradicating two Enterococcus
      faecalis strain biofilms. The biofilms of E. faecalis ATCC 29212 and the clinical
      isolate E. faecalis D1 were grown in the MBEC-high-throughput device for 24 h and
      were exposed to five twofold dilutions of ALX (2%-0.007 8%) alone and combined
      with 100 mg?mL(-1) NAC, for 1 and 5 min. Eradication was defined as 100% kill of
      biofilm bacteria. The Student's t-test was used to compare the efficacy of the
      associations of the two irrigants. After 1-min contact time, ALX eradicated the
      biofilms at all concentrations except for 0.007 8% and 0.015 6%-0.007 8% with E.
      faecalis ATCC 29212 and E. faecalis D1, respectively. Similar results for
      eradication and concentration were obtained when it was combined with 100 mg?mL(
      1) NAC. After 5 min of contact time, ALX alone and combined with NAC eradicated
      all enterococci biofilms. ALX showed antimicrobial properties against the two E.
      faecalis strain biofilms tested at very low concentrations, and its combined use
      with NAC was not seen to enhance its activity. 

PMID- 23970140
TI  - Levels of biological markers of nitric oxide in serum of patients with squamous
      cell carcinoma of the oral cavity.
AB  - The aim of the study was a determination of the levels of nitric oxide (NO) and
      its biological markers such as malonyldialdehyde (MDA) and nitrotyrosine in the
      serum of patients with squamous cell carcinoma (SCC) of the oral cavity and
      identification of the relationships between NO and those markers. These studies
      were performed on patients with SCC of the oral cavity before and after
      treatment. Griess reaction was used for the estimation of the total concentration
      of NO in serum. The nitrotyrosine level in serum was assessed with an enzyme
      linked immunosorbent assay (ELISA) kit, and MDA level using a spectrophotometric
      assay. Higher concentrations of NO in blood serum were determined in patients
      with stage IV of the disease before treatment in comparison to the control group
      and patients with stages II and III of the disease. Moreover, higher
      concentrations of MDA and nitrotyrosine were determined in the serum of patients
      in all stages of the disease in comparison to healthy people. After treatment,
      lower concentrations of NO in the serum of patients with stage IV of the disease
      were observed in comparison to the amounts obtained prior to treatment. In
      addition, lower levels of nitrotyrosine in the serum of patients with all stages
      of the disease were recorded, whereas higher concentrations of MDA were
      determined in these patients in comparison to results obtained before treatment.
      The compounds formed with the contribution of NO, such as MDA and nitrotyrosine,
      may lead to cancer progression in patients with SCC of the oral cavity, and
      contribute to formation of resistance to therapy in these patients as well.
      Moreover, the lack of a relationship between concentrations of NO and MDA, and
      between NO and nitrotyrosine in serum suggests that the process of lipid
      peroxidation and nitration in patients with SCC does not just depend on NO. 

PMID- 23970141
TI  - BMI-specific waist circumference thresholds to discriminate elevated
      cardiometabolic risk in White and African American adults.
AB  - OBJECTIVE: Waist circumference (WC) is a useful anthropometric tool to estimate
      cardiometabolic risk. However, BMI influences the relationship between WC and
      health. This study determined BMI-, sex- and race-specific WC thresholds.
      METHODS: The study sample included 6,452 whites and African Americans (AA) aged
      18-64 years. WC, BMI, and cardiovascular risk factors were assessed in the
      clinic. An elevated cardiometabolic risk was defined as the presence of >=2
      cardiometabolic risk factors. Receiver Operating Characteristic (ROC) curves were
      used to determine BMI-, sex-, and race-specific WC thresholds. RESULTS: Based on
      logistic regression, elevated WC within each BMI category was associated with
      higher cardiometabolic risk. The respective optimal BMI-specific WC thresholds
      for white women, AA women, white men, and AA men were as follows: 72, 76, 82, and
      78 cm for normal-weight (18.5-24.9 kg/m(2)); 87, 85, 95, and 92 cm for overweight
      (25-29.9 kg/m(2)); 97, 97, 107, and 104 cm for obese I (30-34.9 kg/m(2)); and
      111, 110, 120, and 119 cm for obese II+ (>=35 kg/m(2)) participants.
      Sensitivities ranged from 52.7 to 73.3%, and specificities ranged from 57.1 to
      73.5%. CONCLUSION: The proposed optimal BMI-, sex-, and race-specific WC
      thresholds are warranted for use in the clinical setting until representative
      standards become available based on results from longitudinal studies.

PMID- 23970142
TI  - Carrying the pain of abuse: gender-specific findings on the relationship between
      childhood physical abuse and obesity in adulthood.
AB  - BACKGROUND: Childhood abuse has been associated with negative adult health
      outcomes, including obesity. This study sought to investigate the association
      between childhood physical abuse and adult obesity, while controlling for five
      clusters of potentially confounding factors: childhood stressors, socioeconomic
      indicators, marital status, health behaviors, and mental health. METHODS:
      Representative data from the 2005 Canadian Community Health Survey were selected.
      The response rate was approximately 84%. Gender-specific logistic regression
      analyses determined the association between abuse and obesity, while controlling
      for age and race and five clusters of potentially confounding factors. Of the
      12,590 respondents with complete data, 2,787 were obese and 976 reported physical
      abuse as a child or adolescent by someone close to them. RESULTS: Among women
      with childhood physical abuse compared to no abuse, the odds of obesity were 35%
      higher, even when controlling for age, race, and the five clusters of factors
      (odds ratio (OR) = 1.35; 95% confidence interval (CI) = 1.09, 1.67). Childhood
      physical abuse was not associated with adult obesity among men (OR = 1.12; 95% CI
      = 0.82, 1.53). CONCLUSIONS: This study provides one of the first population
      based, gender-specific analyses of the association between childhood physical
      abuse and obesity controlling for a wide range of factors. The gender-specific
      findings require further exploration.

PMID- 23970143
TI  - Association between sleeping hours and siesta and the risk of obesity: the SUN
      Mediterranean Cohort.
AB  - OBJECTIVES: Our aim was to investigate the association between sleeping hours at
      night and during the siesta and the incidence of obesity in a Mediterranean
      cohort. METHODS: After a median of 6.5 years of follow-up, we included 10,532 or
      9,470 participants without chronic disease or obesity at baseline for analyzing
      the association between the incidence of obesity and nocturnal sleep duration or
      having siesta. Sleeping hours and siesta were assessed at baseline. Weight was
      recorded at baseline and every 2 years during the follow-up. The outcome was the
      incidence of obesity during follow-up among participants with initial BMI <30
      kg/m(2). RESULTS: During follow-up we observed 446 new cases of obesity in the
      analysis of nocturnal sleep duration. Sleeping less than 5 h at night was
      associated with a higher risk of becoming obese compared to sleeping between 7
      and <8 h (HR 1.94; 95% CI 1.19-3.18; p for quadratic trend = 0.06) after
      adjusting for potential confounders. During follow-up, we observed 396 incident
      cases of obesity in the analysis of siesta. Those who took a siesta for 30
      min/day had a 33% lower risk of becoming obese (HR 0.67; 95% CI 0.46-0.96; p for
      quadratic trend = 0.13) compared to those who did not take siesta. CONCLUSION:
      Our results suggest that short nocturnal sleep duration could be a modifiable
      risk factor for obesity. It is possible that this association may be stronger
      among men and subjects who experienced previous weight gain. Additionally, siesta
      might be a novel and independent protective factor for obesity; however,
      confirmatory studies are needed.

PMID- 23970144
TI  - Effect of BMI and binge eating on food reward and energy intake: further evidence
      for a binge eating subtype of obesity.
AB  - BACKGROUND: The psychological characteristics of binge eating have been proposed
      as a phenotype to further understanding of overconsumption and susceptibility to
      obesity. This study examined the influence of trait binge eating in lean and
      overweight or obese women on appetite, food reward and energy intake. METHODS: 25
      lean and 25 overweight or obese women were categorised as either 'binge type' or
      'non-binge type' based on their scores on the Binge Eating Scale. Food reward and
      food intake were assessed in fasted and fed conditions. RESULTS: Overweight or
      obese binge types (O-B) consumed more energy than overweight or obese non-binge
      types (O-NB) and lean binge (L-B) and non-binge types (L-NB). Both L-B and O-B
      exhibited greater preference for sweet foods. In O-NB, L-B and L-NB, lower liking
      and wanting for sweet foods was exhibited in the fed condition compared to the
      fasted condition. However, in O-B wanting for sweet foods was greater when they
      were fed compared to when they were in a fasted state. CONCLUSIONS: These
      findings provide further support for trait binge eating as a hedonic subtype of
      obesity. Binge types were characterised by greater intake of high-fat sweet foods
      and increased wanting for these foods when satiated. Additionally, these findings
      highlight the potential for separation in liking and wanting for food as a marker
      of susceptibility to overeat.

PMID- 23970145
TI  - Screening for co-morbidity in 65,397 obese pediatric patients from Germany,
      Austria and Switzerland: adherence to guidelines improved from the year 2000 to
      2010.
AB  - OBJECTIVE: The aim of the study was to analyze the adherence to current
      guidelines for co-morbidity screening in overweight and obese pediatric patients
      participating in the Adipositas-Patienten-Verlaufsdokumentation (APV) initiative
      in three German-speaking countries. METHODS: APV database: 181 centers from
      Germany, Austria and Switzerland, specialized in obesity care, contributed
      standardized, anonymous data of medical examinations from 65,397 patients
      performed between 2000 and 2010. Completeness of screening for hypertension,
      dyslipidemia, and impaired glucose metabolism was analyzed using adjusted means.
      RESULTS: Mean age of the cohort was 12.5 +/- 2.9 years and 46.5% were male. 17.3%
      were overweight (>90th-97th percentile), 45.1% obese (>97th-99.5th percentile),
      and 37.7% extremely obese (>99.5th percentile). In 2000, blood pressure was
      documented for 55.1% of patients, increasing to 88.7% in 2010. The rate of lipid
      diagnostics also improved from 45.0 to 67.7%, and screening for diabetes rose
      from 32.7 to 62.3% in the same time period. Blood pressure measurements were
      performed more often during inpatient care (88.5%) compared to outpatient
      programs (77.5%). Screening was more complete with increasing age and increasing
      degree of obesity. In boys screening rate was higher than in girls. CONCLUSION:
      During the 11-year period, screening for co-morbidity improved significantly in
      overweight or obese children and adolescents. However, adherence to guidelines is
      still insufficient in some institutions. Quality control based on benchmarking
      may improve obesity care and outcome.

PMID- 23970146
TI  - N-3 polyunsaturated fatty acids, body fat and inflammation.
AB  - BACKGROUND: Based on animal studies, n-3 polyunsaturated fatty acids (PUFAs) have
      been suggested to lower the risk of obesity and inflammation. We aimed to
      investigate if, among humans, intake of n-3 PUFAs was associated with i) total
      body fat, ii) body fat distribution and iii) obesity-related inflammatory
      markers. METHODS: The study population consisted of 1,212 healthy individuals
      with information on habitual food intake from food frequency questionnaires, six
      different measures of body fat, and levels of six circulating inflammatory
      markers. Multiple linear regression analysis of intakes of PUFAs in relation to
      outcomes were performed and adjusted for potential confounders. RESULTS: Absolute
      n-3 PUFA intake, but not n-3/n-6, was inversely associated with the different
      measures of body fat. Among n-3 PUFA derivatives, only alpha-linolenic acid (ALA)
      was inversely associated with body fat measures. No significant interactions with
      the dietary macronutrient composition were observed. Pro-inflammatory cytokines
      were not associated with absolute PUFA intake, but the macrophage inflammatory
      protein-1alpha (MIP-1alpha) was associated with the n-3/n-6 ratio. CONCLUSION: In
      humans, intake of n-3 PUFAs, in particular ALA, is beneficially associated with
      body fatness. The favourable association is, however, not reflected in systemic
      levels of pro-inflammatory cytokines, nor is it influenced by macronutrients in
      the diet.

PMID- 23970147
TI  - Dose response association between physical activity and biological, demographic,
      and perceptions of health variables.
AB  - BACKGROUND: Few population-based studies have examined the association between
      physical activity (PA) and cardiovascular disease risk factors, demographic
      variables, and perceptions of health status, and we do not have a clear
      understanding of the dose-response relationship among these variables. METHODS:
      Data from the 2003-2006 National Health and Nutrition Examination Survey was used
      to examine the dose-response relationship between objectively measured PA and
      metabolic syndrome (and its individual cardiovascular disease risk factors),
      demographic variables, and perceptions of health. After exclusions, 5,538
      participants 18 years or older were included in the present study, with 2,538
      participants providing fasting glucose and 2,527 providing fasting triglyceride
      data. PA was categorized into deciles. RESULTS: Overall, the health benefits
      showed a general pattern of increase with each increasing levels of PA. Of the
      ten PA classifications examined, participants in the highest moderate-to-vigorous
      physical activity (MVPA) category (at least 71 min/day) had the lowest odds of
      developing metabolic syndrome. CONCLUSION: At a minimum, sedentary adults should
      strive to meet current PA guidelines (i.e., 150 min/week of MVPA), with
      additional positive benefits associated with engaging in three times this level
      of PA.

PMID- 23970148
TI  - Correlation of resistin with inflammatory and cardiometabolic markers in obese
      adolescents with and without metabolic syndrome.
AB  - OBJECTIVE: The link between plasma resistin and obesity-related cardiometabolic
      disorders in children remains debatable. This study assessed the relationships of
      plasma resistin with cardiovascular risk factors, pro-inflammatory markers and
      insulin resistance index (HOMA-IR) in obese (Ob) adolescents and obese
      adolescents with metabolic syndrome (Ob-MS) compared to healthy controls (CO).
      METHODS: 114 obese adolescents (60 Ob, age 13.6 +/- 0.9 years, BMI 28.0 +/- 2.2
      kg/m(2), and 54 Ob-MS, age 13.8 +/- 1.0 years, BMI 32.5 +/- 4.8 kg/m(2)) and 37
      CO (age 13.7 +/- 0.8 years, BMI 22.8 +/- 0.8 kg/m(2)) were studied.
      Anthropometrics, cardiac variables as well as fasting plasma concentrations of
      lipids, glucose, insulin, and adipocytokines (resistin, tumor necrosis factor
      alpha (TNF-alpha), interleukin-6 (IL-6), C-reactive protein (CRP)) were measured.
      HOMA-IR was calculated, and the presence of MS was assessed. RESULTS: Plasma
      resistin was significantly higher in Ob-MS than in both Ob and CO and was
      correlated with anthropometric, cardiovascular, pro-inflammatory markers and
      several components of MS as was HOMA-IR in Ob and Ob-MS. With increasing the
      number of MS components, plasma resistin, pro-inflammatory markers, and HOMA-IR
      were also increased. Multiple regression models highlighted significant
      correlation between resistin and both HOMA-IR (r = 0.40, p < 0.05) and systolic
      blood pressure (r = 0.63, p < 0.01) in Ob-MS. CONCLUSION: These results support
      the hypothesis that there is an association between circulating resistin and
      childhood obesity-related inflammatory and cardiometabolic events.

PMID- 23970149
TI  - Decline in serum 25 hydroxyvitamin D levels in HIV-HBV-coinfected patients after
      long-term antiretroviral therapy.
AB  - BACKGROUND: Vitamin D insufficiency plays an important role in the development of
      fibrosis in chronic liver disease. METHODS: This was a cross-sectional study from
      Thailand. Liver fibrosis was assessed by transient elastography. Serum 25
      hydroxyvitamin D (25[OH]D)<30 ng/ml was defined as hypovitaminosis D. 25(OH)D was
      assessed prior to and following tenofovir disoproxil fumarate (TDF). Factors
      related to 25(OH)D levels were determined by logistic regression analysis.
      RESULTS: A total of 158 HIV-HBV-coinfected patients (32% female, median age 43
      years) were included. Overall, liver disease was mild with 13.4% having a
      fibrosis score (FS) of 7.1-14 kPa and 2% with a FS>14 kPa. Median (IQR) duration
      on TDF was 5 years (4-7). The median estimated glomerular filtration rate was
      96.9 ml/min/1.73 m(2). The median (IQR) serum 25(OH)D levels prior to and
      following TDF were 24.8 ng/ml (21.3-30.6) and 22.8 ng/ml (18.0-27.7),
      respectively; P<=0.001). The proportion of patients with hypovitaminosis D
      significantly increased from 72.2% (95% CI 64.7, 78.6) prior to TDF to 84.2% (95%
      CI 77.7, 89.0) after taking TDF (P=0.01). Factors associated with hypovitaminosis
      D by multivariate analysis were female sex (adjusted OR 3.8, 95% CI 1.1, 13.7;
      P=0.038) and duration of antiretroviral therapy (ART)>5 years (OR 3.3, 95% CI
      1.2, 8.8; P=0.017). Vitamin D levels were not associated with significant liver
      fibrosis. CONCLUSIONS: Although our HIV-HBV-coinfected patients live in the
      tropics, there was a high prevalence of hypovitaminosis D, especially in female
      patients and those receiving prolonged ART. Since HIV-HBV-coinfection requires
      long-term use of the HBV-active drug, TDF, which can also contribute to bone
      loss, routine vitamin D assessment and supplementation as necessary should be
      considered.

PMID- 23970150
TI  - Aging-related genes in mesenchymal stem cells: a mini-review.
AB  - Adult stem cells in mammalian organs play pivotal roles in the maintenance and
      repair of these organs throughout the life of the adult and maintain the proper
      homeostasis of a tissue or organ. Among the adult stem cells described to date,
      mesenchymal stem cells (MSCs) are highlighted for clinical applications because
      MSCs have many advantages for cell therapy, including multilineage
      differentiation, homing, immune modulation and wound-healing effects. However, as
      the aging of MSCs leads to an age-associated decline in their number and
      function, it is important to clarify the age-associated factors and regulatory
      mechanism associated with the MSC aging process. In this review, we amass and
      discuss the recent data related to age-associated genes in MSCs. In particular,
      the activities of epigenetic regulatory factors, including histone acetylase and
      DNA methyltransferase, modulate gene expression and crosstalk with each other
      during the MSC senescence process. p16(INK4A) and high-mobility group A2 play
      important age-associated roles in the regulation of MSC stemness, and lamin A-
      and prelamin A-dependent nuclear abnormalities have significant biological
      relevance in MSC aging. Taken together, the information described here, including
      the epigenetic regulatory factors, transcription factors and cell signaling,
      could be used toward the development of treatments for MSC aging and related
      defects. 

PMID- 23970151
TI  - Impact factor. Editorial.

PMID- 23970152
TI  - A novel and objective pathological classification system for radical hysterectomy
      (RH): an initial proposal.

PMID- 23970153
TI  - Randomized study of aggressive surgery for advanced ovarian cancer.

PMID- 23970154
TI  - Association between reproductive cancer and fetal outcomes: a systematic review.
AB  - OBJECTIVE: This study aimed to review studies that addressed the impact of
      previous reproductive cancer diagnosis on selected fetal birth outcomes.
      MATERIALS AND METHODS: We searched PubMed and Web of Knowledge to identify peer
      reviewed articles published from January 1992 to December 2012, investigating the
      association between reproductive cancer and birth outcomes. After applying
      exclusion criteria, 49 articles were identified for full review, and 36 articles
      were finally selected for this systematic review. The quality of the studies was
      assessed by independent reviewers. RESULTS: We found 13 cervical cancer studies,
      16 ovarian cancer studies, and 7 corpus uteri cancers that reported subsequent
      pregnancies (n = 688 pregnancies in 477 women). Of these, 489 pregnancies reached
      third trimester. Among viable pregnancies, only 416 pregnancies had information
      on maturity status based on gestational age and/or birth weight. For those with
      cervical cancer, the preterm birth (PTB) rate was 48.5%. For those with ovarian
      cancer, there were no cases of PTB. For those with corpus uteri cancers, the PTB
      was 7.7%. All studies had small sample sizes, and there was considerable
      heterogeneity of results. Abortions, ectopic pregnancies, and terminations were
      also reported. CONCLUSIONS: Reproductive cancers may be associated to subsequent
      adverse fetal birth outcomes; however, the quality of evidence is still
      insufficient to infer a relationship between reproductive cancers treated
      conservatively and adverse fetal birth outcomes in subsequent pregnancies.

PMID- 23970155
TI  - Basic T1 Perfusion magnetic resonance imaging evaluation of the therapeutic
      effect of neoadjuvant chemotherapy in locally advanced cervical cancer.
AB  - OBJECTIVE: The objective of this study was to evaluate the dynamic changes of
      blood perfusion coinciding with tumor regression after neoadjuvant chemotherapy
      (NACT) in locally advanced cervical cancer (LACC). METHODS: Thirty patients with
      LACC received conventional 3.0-T magnetic resonance imaging and perfusion
      weighted imaging scans at 3 different times (before NACT, 2 weeks after the first
      NACT, and 2 weeks after the second NACT). Characteristics of time-intensity
      diagrams and patterns of blood perfusion maps according to the parameter of area
      under the curve (AUC) were observed. Eight perfusion parameters were compared
      among 3 time points at 2 different chemotherapy-sensitive groups by the software
      of Basic T1 Perfusion. RESULTS: The effective chemotherapy rate was 73.3%
      (22/30). The characteristic of time-intensity diagrams in cervical cancer was a
      rapid onset with plateau. There were 3 patterns of AUC perfusion maps. The common
      perfusion map was rich blood supply type in the effective chemotherapy group and
      peripheral blood supply type in the ineffective chemotherapy group. Four
      parameter values (relative enhancement, maximum enhancement, wash-in rate, and
      AUC) were significantly reduced 2 weeks after the second NACT than those before
      the therapy (P = 0.000; P = 0.009; P = 0.011; and P = 0.000) in the effective
      chemotherapy group, especially the value of relative enhancement 2 weeks after
      the first NACT, was obviously decreased compared to that before the therapy (P =
      0.042). The value of time to peak 2 weeks after the second NACT was significantly
      longer than that before the therapy in the effective chemotherapy group (P =
      0.001). There were no obvious changes of blood perfusion parameters among the 3
      different times in the ineffective chemotherapy group. CONCLUSIONS: Tumor blood
      perfusion has obviously decreased after effective NACT in the treatment of LACC.

PMID- 23970156
TI  - Multiple-type human papillomavirus (HPV) infections: a cross-sectional analysis
      of the prevalence of specific types in 309,000 women referred for HPV testing at
      the time of cervical cytology.
AB  - OBJECTIVES: To determine the frequency of multiple-type cervical human
      papillomavirus (HPV) infections, and whether any types are involved in multiple
      type infections more or less frequently than might be expected if these
      infections occur randomly. METHODS: In this retrospective analysis of type
      specific HPV testing, results from women 18 to 65 years old with samples
      collected between July 2007 and May 2011 were considered.Multivariate logistic
      regression analysis was used to model the presence of each of the 24 most
      prevalent HPV types, adjusting for one other HPV type, age, laboratory region,
      and age-by-region interactions. RESULTS: Human papillomavirus infection was
      present in 74,543 (24.1%) of 309,471 women and 65,492 (21.1%) were positive for
      one of the top 24 most prevalent HPV types. The most common HPV type was type 16,
      occurring in 4.1% of the entire sample. A total of 14,181 women were positive for
      2 or more HPV types (4.6% of entire sample and 19.0% of HPV-positive sample). Two
      way HPV type comparisons were analyzed. Types 52, 53, 81, and 83 were more likely
      to occur in multiple infections with other types; and types 16, 58, and 66 were
      less likely to occur in multiple infections with other types. Human
      papillomavirus types 72 and 81 have the strongest positive relationship (odds
      ratio, 5.2; 95% confidence interval, 3.6-7.4). Human papillomavirus types 33 and
      66 have the strongest negative relationship (odds ratio, 0.4; 95% confidence
      interval, 0.2-0.6). CONCLUSIONS: In this population, multiple-type HPV infections
      were present in 4.6% of all women. Our findings suggest that there may be both
      competitive and cooperative interactions between HPV types.

PMID- 23970157
TI  - High-dose chemotherapy with autologous stem cell support as salvage therapy in
      recurrent gestational trophoblastic disease.
AB  - BACKGROUND: Gestational trophoblastic disease usually follows a molar pregnancy
      but can occur also after an abortion or a term pregnancy. In only 10% of cases
      will treatment be required; and usually, single-agent chemotherapy will suffice.
      In high-risk disease, the multiagent regimen EMA-CO is usually used; and if that
      fails, most oncologists will use the EMA-EP regimen. If this does not produce a
      remission, there is no unanimity of opinion as to how to proceed. Numerous
      salvage regimens are in current use, and some centers do not consider high-dose
      chemotherapy. CASE: A young woman presented 4 months after a normal spontaneous
      delivery with an elevated human chorionic gonadotropin level and multiple
      pulmonary metastases. She failed both the EMA-CO and EMA-EP regimens as well as
      additional standard chemotherapy. She was then treated with 4 separate courses of
      high-dose chemotherapy with autologous stem cell support, which produced a
      complete remission. CONCLUSION: Even patients with high-risk gestational
      trophoblastic disease are usually cured with standard chemotherapy. Patients who
      fail such treatment should be considered for high-dose chemotherapy.

PMID- 23970158
TI  - Epithelioid trophoblastic tumor: an outcome-based literature review of 78
      reported cases.
AB  - OBJECTIVES: Epithelioid trophoblastic tumor (ETT) is very rare; and therefore, a
      substantially increased data set is unlikely to be obtained in the near future.
      This analysis aimed to assess the effects of current management on clinical
      outcomes and to identify potential prognostic indicators in ETT. METHODS: We
      applied a literature search using PubMed to analyze the clinical data of 78
      published cases of ETT. RESULTS: Women with ETT present at reproductive age (mean
      +/- SD, 37.1 +/- 8.7 years) and have a slightly to moderately elevated serum beta
      human chorionic gonadotropin (median, 665 IU/L). Epithelioid trophoblastic tumor
      is frequently present in the lower uterine segment/cervix (26/58 cases) and can
      be misdiagnosed as squamous cell carcinoma (6/26). Lung is the most common
      extrauterine site of ETT (5/11 with uterine ETT and 10/20 without uterine ETT).
      Kaplan-Meier analysis indicates that chemotherapy (surgery with postoperative
      chemotherapy vs surgery alone) is associated with increased ETT relapse (P =
      0.005), even after stratification by International Federation of Gynecology and
      Obstetrics (FIGO) stage (P = 0.008); but FIGO stage remains the only significant
      prognostic indicator for ETT (P = 0.015). CONCLUSIONS: This analysis confirms the
      hypothetical chemotherapy resistance and prognostic value of FIGO staging in ETT.
      These findings remain tentative given the small data set available for analysis
      and the reporting bias from these published cases; however, they may confer a
      risk-adapted therapy. Finally, both gynecologists and pathologists should be
      alert to the potential misdiagnosis of squamous cell carcinoma when ETT is
      present in the lower uterine segment/cervix.

PMID- 23970160
TI  - Retraction.

PMID- 23970159
TI  - Roadmap for the European Network of Gynaecological Trial groups (ENGOT) Trials.
AB  - The European Network for Gynaecological Oncological Trial groups (ENGOT) is a
      research network of the European Society of Gynaecological Oncology and was
      founded in Berlin in October 2007. Earlier, we reported on the ENGOT minimal
      requirements for trials between academic groups and pharmaceutical companies. In
      this paper, we summarize the roadmap for performing trials in the ENGOT
      framework. In this roadmap, we define how an ENGOT trial should be set up and
      discuss the following items: What are the conditions to classify a study as an
      ENGOT trial? What is an ENGOT protocol? How are an ENGOT protocol, informed
      consent (ICF), and case report form (CRF) produced? How is the center selection
      and feasibility performed in ENGOT trials? How are regulatory and operational
      tasks handled? How should a confidentiality agreement between the industry and
      the whole ENGOT network be negotiated? How are contracts made between the
      industry and ENGOT and between ENGOT groups? How are funding, insurance, and
      communication flow arranged in ENGOT trials? What are the requirements for
      conducting substudies and what are the tasks for the leading group in an ENGOT
      trial? A template of a confidentiality agreement, a checklist of ENGOT criteria
      for new study proposals, and guidelines for authorship are also provided. 

PMID- 23970161
TI  - Methylation of nucleolar and coiled-body phosphoprotein 1 is associated with the
      mechanism of tumorigenesis in hepatocellular carcinoma.
AB  - Nucleolar and coiled-body phosphoprotein 1 (NOLC1) plays an essential role in the
      synthesis of rRNA and the biosynthesis of ribosomes. Previous studies suggest
      that NOLC1 is crucial for normal cell growth, and plays a role in the regulation
      of tumorigenesis of nasopharyngeal carcinoma (NPC) and demonstrate that both
      NOLC1 and tumor protein 53 work synergistically to activate the MDM2 promoter in
      NPC cells. Yet, the functioning of NOLC1 in liver cancer remains unknown. The aim
      of the present study was to understand how the NOLC1 gene is regulated in liver
      carcinogenesis. In this study, we showed that NOLC1 was silenced or downregulated
      in liver tumor tissues when compared with that in the matched non-cancer tissues.
      In addition, human hepatoma cells weakly expressed NOLC1, whereas cultured human
      normal liver cell lines expressed abundant levels. The hypermethylation status in
      the promoter CpG1 start region appeared to be correlated with the NOLC1
      expression levels in liver cell lines or liver normal and tissue specimens. We
      found that four CpG dinucleotides were located at the CpG1 start region. Further
      molecular analysis of mutagenesis indicated that the four CpG dinucleotides play
      a role in the promoter activity of the NOLC1 gene. The expression of NOLC1 and
      DNA methylation of its promoter affected cell proliferation and apoptosis. The
      expression of NOLC1 in hepatoma cell lines was restored following exposure to the
      demethylation agent, 5-azacytidine. Low expression of NOLC1 in hepatoma cell
      lines and liver cancer tissues was associated with cyclin D3. In conclusion, our
      study demonstrated that DNA methylation is a key mechanism of silenced NOLC1
      expression in human hepatocellular carcinoma cells, and NOLC1 gene
      hypermethylation of the four CpG dinucleotides is a potential biomarker for
      hepatocellular carcinoma. 

PMID- 23970162
TI  - Inhibitory effect of TGF-beta1 on NO production in peritoneal macrophages from
      collagen-induced arthritis rats involving the LPS-TLR4 pathway.
AB  - Transforming growth factor-beta1 (TGF-beta1) is critical in controlling
      inflammatory responses and the prevention of autoimmune diseases. Although the
      effect of TGF-beta1 on macrophages from normal mice or rats has been established,
      little attention has been paid to its effect on disease conditions. In the
      present study, we investigated the regulatory effect, and possible mechanism, of
      TGF-beta1 exposure on the secretion of nitric oxide (NO) in peritoneal
      macrophages (PMPhi) obtained from collagen-induced arthritis (CIA) rats. The CIA
      model was established by immunizing the emulsion of collagen type II and
      incomplete Freund's adjuvant (IFA) in Wistar rats. PMPhi were incubated with TGF
      beta1 (5 ng/ml) for 36 h and the supernatant, and cell mRNA and protein were
      collected. NO concentration was determined using an NO assay kit. The mRNA
      expression of inducible nitric oxide synthase (iNOS) and Toll-like receptor 4
      (TLR4) was determined using reverse transcription-polymerase chain reaction (RT
      PCR). The protein expression of iNOS was tested with western blot analysis. The
      expression of membrane TLR4 was determined by flow cytometry. We discovered that
      the secretion of NO from the PMPhi of CIA rats increased compared with normal
      rats. TGF-beta1 significantly inhibited the production of NO in the PMPhi from
      CIA rats. iNOS mRNA and protein expression in the PMPhi from CIA rats may be
      suppressed by TGF-beta1. TLR4 mRNA and protein expression in PMPhi from CIA rats
      were upregulated with LPS stimulation and treatment with TGF-beta1 inhibited
      their expression. These results demonstrated that TGF-beta1 inhibited
      lipopolysaccharide (LPS)-induced NO production in the PMPhi from CIA rats, which
      may be due to the inhibition of the LPS-TLR4 signaling pathway.

PMID- 23970163
TI  - Surface reactivity enhancement on a Pd/Bi2Te3 heterostructure through robust
      topological surface states.
AB  - We present a study of the surface reactivity of a Pd/Bi2Te3 thin film
      heterostructure. The topological surface states from Bi2Te3, being delocalized
      and robust owing to their topological natures, were found to act as an effective
      electron bath that significantly enhances the surface reactivity of palladium in
      the presence of two oxidizing agents, oxygen and tellurium respectively, which is
      consistent with a theoretical calculation. The surface reactivity of the adsorbed
      tellurium on this heterostructure is also intensified possibly benefitted from
      the effective transfer of the bath electrons. A partially inserted iron
      ferromagnetic layer at the interface of this heterostructure was found to play
      two competing roles arising from the higher-lying d-band center of the Pd/Fe
      bilayer and the interaction between the ferromagnetism and the surface spin
      texture of Bi2Te3 on the surface reactivity and their characteristics also
      demonstrate that the electron bath effect is long-lasting against accumulated
      thickness of adsorbates. 

PMID- 23970164
TI  - Modulation of intracellular calcium homeostasis blocks autophagosome formation.
AB  - Cellular stress responses often involve elevation of cytosolic calcium levels,
      and this has been suggested to stimulate autophagy. Here, however, we
      demonstrated that agents that alter intracellular calcium ion homeostasis and
      induce ER stress-the calcium ionophore A23187 and the sarco/endoplasmic reticulum
      Ca (2+)-ATPase inhibitor thapsigargin (TG)-potently inhibit autophagy. This anti
      autophagic effect occurred under both nutrient-rich and amino acid starvation
      conditions, and was reflected by a strong reduction in autophagic degradation of
      long-lived proteins. Furthermore, we found that the calcium-modulating agents
      inhibited autophagosome biogenesis at a step after the acquisition of WIPI1, but
      prior to the closure of the autophagosome. The latter was evident from the
      virtually complete inability of A23187- or TG-treated cells to sequester
      cytosolic lactate dehydrogenase. Moreover, we observed a decrease in both the
      number and size of starvation-induced EGFP-LC3 puncta as well as reduced numbers
      of mRFP-LC3 puncta in a tandem fluorescent mRFP-EGFP-LC3 cell line. The anti
      autophagic effect of A23187 and TG was independent of ER stress, as chemical or
      siRNA-mediated inhibition of the unfolded protein response did not alter the
      ability of the calcium modulators to block autophagy. Finally, and remarkably, we
      found that the anti-autophagic activity of the calcium modulators did not require
      sustained or bulk changes in cytosolic calcium levels. In conclusion, we propose
      that local perturbations in intracellular calcium levels can exert inhibitory
      effects on autophagy at the stage of autophagosome expansion and closure. 

PMID- 23970165
TI  - Laparoscopic and open subtotal colectomies have similar short-term results.
AB  - BACKGROUND: Laparoscopic subtotal colectomy (STC) is a complex procedure. It is
      possible that short-term benefits for segmental resections cannot be attributed
      to this complex procedure. This study aims to assess differences in short-term
      results for laparoscopic versus open STC during a 15-year single-institute
      experience. METHODS: We reviewed consecutive patients undergoing laparoscopic or
      open elective or subacute STC from January 1997 to December 2012. RESULTS: Fifty
      six laparoscopic and 50 open STCs were performed. The operation time was
      significantly longer in the laparoscopic group, median 266 min (range 121-420
      min), compared to 153 min (range 90-408 min) in the open group (p < 0.001).
      Median hospital stay showed no statistical difference, 14 days (range 1-129 days)
      in the laparoscopic and 13 days (range 1-85 days) in the open group. Between
      group postoperative complications were not statistically different. CONCLUSIONS:
      Laparoscopic STC has short-term results similar to the open procedure, except for
      a longer operation time. The laparoscopic approach for STC is therefore only
      advisable in selected patients combined with extensive preoperative counseling.

PMID- 23970167
TI  - Chemical tuning of electrochemical properties of Pt-skin surfaces for highly
      active oxygen reduction reactions.
AB  - Pt-skin surfaces were successfully fabricated by the chemical deposition of
      additional Pt on corrugated Pt-Ni nanoparticles with Pt-skeleton surfaces.
      Compared to the Pt-skin formed by heat annealing, the chemically-tuned Pt-skin
      had a higher Pt coordination number and surface crystallinity, which resulted in
      superior ORR activity and durability. 

PMID- 23970166
TI  - Chemical principles for the design of a novel fluorescent probe with high cancer
      targeting selectivity and sensitivity.
AB  - Understanding of principles governing selective and sensitive cancer targeting is
      critical for development of chemicals for cancer diagnostics and treatment. We
      determined the underlying mechanisms of how a novel fluorescent small organic
      molecule, 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC),
      selectively labels cancer cells but not normal cells. We show that BMVC is
      retained in the lysosomes of normal cells. In cancer cells, BMVC escapes
      lysosomal retention and localizes to the mitochondria or to the nucleus, where
      DNA-binding dramatically increases BMVC fluorescence intensity, allowing it to
      light up only cancer cells. Structure-function analyses of BMVC derivatives show
      that hydrogen-bonding capacity is a key determinant of lysosomal retention in
      normal cells, whereas lipophilicity directs these derivatives to the mitochondria
      or the nucleus in cancer cells. In addition, drug-resistant cancer cells
      preferentially retain BMVC in their lysosomes compared to drug-sensitive cancer
      cells, and BMVC can be released from drug-resistant lysosomes using
      lysosomotropic agents. Our results further our understanding of how properties of
      cellular organelles differ between normal and cancer cells, which can be
      exploited for diagnostic and/or therapeutic use. We also provide physiochemical
      design principles for selective targeting of small molecules to different
      organelles. Moreover, our results suggest that agents which can increase
      lysosomal membrane permeability may re-sensitize drug-resistant cancer cells to
      chemotherapeutic agents. 

PMID- 23970168
TI  - Expression of lysyl oxidase in human osteosarcoma and its clinical significance:
      a tumor suppressive role of LOX in human osteosarcoma cells.
AB  - Lysyl oxidase (LOX) is an extracellular matrix (ECM) remodeling enzyme, which is
      involved in the development and progression of many types of tumors. LOX
      dysfunction is observed in colorectal, breast and ovarian cancer. However, the
      precise effects and molecular mechanisms of LOX action in osteosarcoma
      progression are still unknown. We evaluated the role of LOX in human osteosarcoma
      cell lines and clinical tumor samples in order to determine the function of this
      molecule. In our study, we showed that the expression level of LOX mRNA and
      protein were decreased in human osteosarcoma tissues as compared with normal
      tissue samples. In addition, we employed adenovirus-mediated overexpression of
      LOX in U-2OS and HOS cells to investigate the role of LOX in osteosarcoma cell
      lines. Adenovirus-mediated overexpression of LOX could efficiently increase the
      expression levels of LOX in osteosarcoma cell lines at both mRNA and protein
      levels. Increased expression of LOX inhibited the proliferation and migration of
      human osteosarcoma cells and promoted its apoptosis. Moreover, the Ki-67 and PCNA
      expression was decreased and MMP-2 and MMP-9 expression was inhibited. These
      findings also indicated that the effects of LOX may be mediated via the PI3K/AKT
      signaling pathway since LOX-mediated functions could be blocked by beta
      aminopropionitrile (beta-APN), a LOX inhibitor. Taken together, our data
      indicated that LOX may be a tumor suppressor and could be regarded as a
      therapeutic target in human osteosarcoma. 

PMID- 23970169
TI  - Both chronic kidney disease and nocturnal blood pressure associate with strokes
      in the elderly.
AB  - BACKGROUND: Among elderly hypertensive patients, we aimed to assess the
      association of nocturnal blood pressure (BP) pattern on stroke; interaction of
      dipping pattern with kidney disease was explored. METHODS: We retrospectively
      analyzed the records of 1,276 elderly (>=60 years) hypertensive Japanese patients
      (mean 74 years; 40% were men) who had measurements of estimated glomerular
      filtration rate and ambulatory BP. RESULTS: Stroke events occurred in 73 people
      over an average of 3.2 years (4,026 person-years). Chronic kidney disease (CKD)
      at baseline (n = 634, 50%) was more prevalent in people with strokes (71%) than
      those without strokes (48%; p < 0.01). Both CKD and nocturnal systolic BP (SBP)
      increase (10 mm Hg) were independently associated with increased risk for stroke
      [hazard ratio (HR), 1.9; 95% confidence interval (CI), 1.1-3.1 for CKD and HR
      1.2; 1.1-1.4 for SBP]. After adjustment for office SBP, a 10-mm Hg increase in
      nocturnal SBP was similarly associated with strokes in patients with CKD (HR 1.2;
      95% CI 1.0-1.3) and those without CKD (HR 1.2; 95% CI 0.97-1.5). Although reverse
      dipping (nocturnal SBP >= daytime SBP) was associated with stroke only in
      patients with CKD (HR 2.1; 95% CI 1.1-4.1) and not those without CKD (HR 1.1; 95%
      CI 0.3-3.8), the interaction effect was not significant (p = 0.30). CONCLUSION:
      In elderly hypertensive patients, both high nocturnal SBP and CKD are independent
      risk factors for stroke.

PMID- 23970170
TI  - [Gender relations and interdependence: reflections on changes in the hospital
      configuration].
AB  - The article analyzes changes that have occurred in hospitals over the years, with
      a focus on the dynamics of gender relations as experienced by healthcare workers.
      We use the notions of configuration and interdependence, taken from Norbert
      Elias' theory of the civilizing process, along with discussions of gender
      relations at work; drawing from Michel Foucault, we also reference the
      disciplinary practices employed down through hospital history. This linkage of
      discussions on gender issues and on interdependent relations opens up to a
      reflection on conflicts of interests, power struggles, and the balance of
      tensions, which in turn makes it possible to problematize gender inequalities
      with the ultimate aim of achieving an interdisciplinary effort that will promote
      health care of an integral nature. 

PMID- 23970171
TI  - Quetelet, the average man and medical knowledge.
AB  - Using two books by Adolphe Quetelet, I analyze his theory of the 'average man',
      which associates biological and social normality with the frequency with which
      certain characteristics appear in a population. The books are Sur l'homme et le
      developpement de ses facultes and Du systeme social et des lois qui le regissent.
      Both reveal that Quetelet's ideas are permeated by explanatory strategies drawn
      from physics and astronomy, and also by discursive strategies drawn from theology
      and religion. The stability of the mean as opposed to the dispersion of
      individual characteristics and events provided the basis for the use of
      statistics in social sciences and medicine. 

PMID- 23970172
TI  - [The construction of the 'SUS problem' in the newspaper Folha de S. Paulo].
AB  - The article examines the process of discursive construction of the 'SUS problem'
      in reports published in the newspaper Folha de S. Paulo in 2008. Through an
      online search of the Folha archives, 667 news items were selected and then
      studied from the perspectives of critical discourse analysis and contributions
      from social constructionism. In methodological terms, at the text practice level
      of analysis, the investigation sought to determine what linguistic resources had
      been used to construct the SUS problem. At the discursive practice level of
      analysis, it further explored how the newspaper medium and the journalistic style
      influenced the production of these meanings. The article concludes that as this
      production constructs the SUS problem, it fosters a limited, negative view of the
      the Sistema Unico de Saude (Unified Healthcare System, or SUS) based on mistrust
      and on the notion that it is impossible to improve the system. 

PMID- 23970173
TI  - [Adolphe Quetelet and biopolitics as secularized theology].
AB  - The article recaptures the work of an author who has been forgotten by the
      contemporary social sciences, that is, the Belgium polymath Adolphe Quetelet.
      Focusing on his main work, Sur l'homme et le developpement de ses facultes, ou
      Essai de physique sociale, the study underscores how the secularization of
      theological principles within the realm of science was important to the
      construction of Quetelet's work. His dual engagement in science and politics is
      pertinent here, as he was the main nineteenth-century force behind the
      incorporation of statistics as a science essential to the State's ability to
      govern its people. He also played a relevant role in the realization of the
      hegemonic political project of modernity, biopolitics, and its influence in the
      field of biomedicine in the nineteenth and twentieth centuries. 

PMID- 23970174
TI  - Sulfidation of silver nanowires inside human alveolar epithelial cells: a
      potential detoxification mechanism.
AB  - Silver nanowires (AgNWs) are being developed for use in optoelectronics. However
      before widespread usage, it is crucial to determine their potential effects on
      human health. It is accepted that Ag nanoparticles (AgNPs) exert toxic effects by
      releasing Ag(+) ions, but much less is known about whether Ag(+) reacts with
      compounds, or any downstream bioactive effects of transformed AgNPs. Analytical
      high-resolution transmission electron microscopy has been employed to elucidate
      cellular uptake and reactivity of AgNWs inside human alveolar epithelial type 1
      like cells. AgNWs were observed in the cytoplasm and membrane-bound vesicles, and
      precipitation of Ag2S within the cell occurred after 1 h exposure. Cell viability
      studies showed no evidence of cytotoxicity and reactive oxygen species were not
      observed on exposure of cells to AgNWs. We suggest that Ag2S formation acts as a
      'trap' for free Ag(+), significantly limiting short-term toxicological effects -
      with important consequences for the safety of Ag-nanomaterials to human health. 

PMID- 23970175
TI  - Tetrathiafulvalene-annulated [28]hexaphyrin(1.1.1.1.1.1): a multi-electron donor
      system subject to conformational control.
AB  - Tetrathiafulvalenes (TTF)-annulated [28]hexaphyrin affords an electron rich
      flexible pi-conjugated system whose limiting conformations can be controlled
      through choice of solvents. The conformation-dependent intramolecular charge
      transfer character, as well as electron reserve capability of the hexakis-TTF
      annulated hexaphyrin, was analyzed. 

PMID- 23970176
TI  - The advantage of using 3-week data to predict response to aripiprazole at week 6
      in first-episode psychosis.
AB  - We investigated the efficacy and safety of aripiprazole in first-episode
      psychosis and explored the association between early response and later response
      to this medication. This was a 6-week, open-label, multicenter trial. The study
      population consisted of 59 patients with a DSM-IV diagnosis of a schizophreniform
      disorder, schizoaffective disorder, schizophrenia, or psychotic disorder not
      otherwise specified. The primary outcome measures were the Positive and Negative
      Syndrome Scale (PANSS) and the Clinical Global Impression-Severity scale. To
      assess the safety, we measured the drug-related adverse events, weight, and lipid
      related variables. The sensitivity, specificity, positive predictive value, and
      negative predictive value were calculated for the response status at weeks 2 and
      3 to predict the subsequent response at week 6. Among the 59 participants, 38
      were able to complete the 6-week trial. Treatment with aripiprazole resulted in
      significant improvement in the PANSS and Clinical Global Impression scores over
      time. The response rate (defined as a >=30% decrease in the PANSS total score
      from baseline to the last observation) was 69.1%. The most accurate prediction of
      later response in terms of negative predictive value and specificity was a
      reduction in the PANSS total score from baseline to week 3 of at least 20%.
      Aripiprazole had a modest side effect burden and was characterized by a safe
      profile with respect to weight and metabolic side effects. These results indicate
      that aripiprazole is effective and safe in the treatment of first-episode
      psychosis. The response at week 3, rather than week 2, predicted the later
      response more accurately. 

PMID- 23970177
TI  - Comment on 'Epicardial adipose tissue increased in patients with newly diagnosed
      subclinical hypothyroidism'.

PMID- 23970180
TI  - Oncogenic chromosomal translocations and human cancer (review).
AB  - Chromosomal translocations are very common in human cancer. The molecular
      mechanisms of chromosomal translocations are complex and are not fully
      understood. Recent studies showed organization of genomes is higher-order in the
      nucleus and every chromosome or chromatin has its preferential position and
      territory. These findings suggest the spatial arrangements of chromosomes and
      gene loci in the interphase nucleus are responsible for non-random chromosomal
      translocations in human cancer. Chromosomal translocations are favored in
      neighboring chromosomes or genes in spatial proximity within the nucleus.
      Chromosomal translocations leading to cancer are generally via two ways,
      formation of oncogenic fusion protein or oncogene activation by a new promoter or
      enhancer. This review focuses mainly on the recent advances in oncogenic
      chromosomal translocations in human cancer. 

PMID- 23970178
TI  - Induction of Pax3 gene expression impedes cardiac differentiation.
AB  - Cell-based therapies using pluripotent stem cells hold great promise as
      regenerative approaches to treat many types of diseases. Nevertheless many
      challenges remain and, perhaps foremost, is the issue of how to direct and
      enhance the specification and differentiation of a desired cell type for
      potential therapeutics. We have examined the molecular basis for the inverse
      correlation of cardiac and skeletal myogenesis in small molecule-enhanced stem
      cell differentiation. Our study shows that activation of premyogenic factor Pax3
      coincides with inhibiting gene expression of early cardiac factor GATA4.
      Interestingly, the inhibitory effect of small molecules on cardiac
      differentiation depends on the function of Pax3, but not the mesoderm factor
      Meox1. Thus Pax3 is an inhibitor of cardiac differentiation in lineage
      specification. Our studies reveal the dual roles of Pax3 in stem cell fate
      determinations and provide new molecular insights into small molecule-enhanced
      lineage specification. 

PMID- 23970181
TI  - Late onset tuberculosis infection in patients receiving anti-TNFalpha therapy.

PMID- 23970179
TI  - Apolipoprotein A5 gene variants and the risk of coronary heart disease: a case
      control study and meta-analysis.
AB  - Previous studies have shown that apolipoprotein A5 (APOA5) gene variants are
      genetic determinants of the concentration of triglycerides, which are a known
      risk factor for coronary heart disease (CHD). Using the standardized coronary
      angiography method, 290 CHD patients and 198 non-CHD controls were recruited from
      Ningbo Lihuili Hospital. In addition, 331 unrelated healthy volunteers were
      recruited as healthy controls from Ningbo Ximen Community residents. Three
      variants of the APOA5 gene, S19W, -1131T>C and 553G>T, were analyzed for their
      association with CHD. Under a dominant inheritance model, -1131CT>C was shown to
      be a CHD risk factor (P=0.030; OR, 1.422; 95% CI, 1.036-1.952). The single
      nucleotide polymorphism, 553G>T, was found to correlate with the severity of CHD
      in males (P=0.032). Meta-analysis showed that -1131T>C was significantly
      associated with CHD (P<0.0001). By contrast, negative correlations with CHD were
      observed for S19W and 553G>T. In the present case-control study, APOA5 gene
      variants were not found to correlate with the risk of CHD in the populations
      studied; however, -1131CT>C was shown to be a CHD risk factor under a dominant
      inheritance model. Meta-analysis showed a significant contribution of -1131T>C to
      the risk of CHD, implying an ethnic difference in APOA5 gene variants.

PMID- 23970182
TI  - Rhabdomyolysis after fish consumption: Haff's disease.

PMID- 23970183
TI  - The effect of a large Legionnaires' disease outbreak in Southwest Edinburgh on
      acute and critical care services.
AB  - OBJECTIVE: The largest outbreak of Legionnaires Disease (LD) in the UK for a
      decade occurred in Edinburgh in June 2012. We describe the clinical and public
      health management of the outbreak. SETTING: Three acute hospitals covering an
      urban area of ~480,000. METHODS: Data were collected on confirmed and suspected
      cases and minutes of the Incident Management Team meetings were reviewed to
      identify key actions. RESULTS: Over 1600 urine samples and over 600 sputum
      samples were tested during the outbreak. 61 patients with pneumonia tested
      positive for Legionella pneumophila serogroup 1 by urinary antigen detection,
      culture, respiratory PCR or serology. A further 23 patients with pneumonia were
      treated as suspected cases on clinical and epidemiological grounds but had no
      microbiological diagnosis. 36% of confirmed and probable cases required critical
      care admission. Mean ICU length of stay was 11.3 (+/-7.6) days and mean hospital
      length of stay for those who were admitted to ICU was 23.0 (+/-17.2) days. For
      all hospitalized patients the mean length of stay was 15.7 (+/-14) days. In total
      there were four deaths associated with this outbreak giving an overall case
      fatality of 6.5%. Hospital and critical care mortality was 6.1% and 9.1%,
      respectively. CONCLUSION: A significant proportion of patients required prolonged
      multiple organ support or complex ventilation. Case fatality compared favourably
      to other recent outbreaks in Europe. Access to rapid diagnostic tests and prompt
      antibiotic therapy may have mitigated the impact of pre-existing poor health
      among those affected.

PMID- 23970184
TI  - RE: 'Treatment outcome in adults with chronic fatigue syndrome: a prospective
      study.

PMID- 23970185
TI  - Achromobacter xylosoxidans meningitis in an immunosuppressed patient.

PMID- 23970186
TI  - Mosquito bites and eastern equine encephalitis.

PMID- 23970187
TI  - Rice body--Mycobacterium intracellulare tenosynovitis.

PMID- 23970188
TI  - Response to Derek Enlander.

PMID- 23970189
TI  - Association between frailty and dementia: a population-based study.
AB  - BACKGROUND: Frailty is commonly considered as a syndrome with several symptoms,
      including weight loss, exhaustion, weakness, slow walking speed and physical
      inactivity. It has been suggested that cognitive impairment should be included in
      the frailty index, however the association between frailty and cognition has not
      yet been fully established. OBJECTIVE: To investigate cross-sectionally whether
      frailty is associated with cognitive impairment or clinically diagnosed dementia
      in older people. METHODS: The study included a total of 654 persons aged 76-100
      years (mean 82 +/- 4.6). Frailty status of the participants was assessed using
      the Cardiovascular Health Study criteria. Cognitive function was assessed with
      the Mini-Mental State Examination (MMSE). Clinically diagnosed dementia was
      assessed by specialists using diagnostic criteria. The associations between
      frailty and cognition were investigated using logistic regression. RESULTS: A
      total of 93 (14%) participants were classified as frail. Cognitive impairment
      (MMSE score <25) was observed among 171 (26%) persons and 134 (21%) persons had
      clinically diagnosed dementia. 97 (15%) persons had Alzheimer's disease, 19 (3%)
      had vascular dementia, 12 (2%) had dementia with Lewy bodies and 8 persons (1%)
      had some other type of dementia. Multivariate logistic regression models showed
      that frail persons were almost 8 times more likely to have cognitive impairment
      (OR 7.8, 95% CI 4.0-15.0), 8 times more likely to have some kind of dementia (OR
      8.0, 95% CI 4.0-15.9), almost 6 times more likely to have vascular dementia (OR
      5.6, 95% CI 1.2-25.8) and over 4 times more likely to have Alzheimer's disease
      (OR 4.5, 95% CI 2.1-9.6) than persons who were robust. CONCLUSION: Frailty is
      strongly associated with cognitive impairment and clinically diagnosed dementia
      among persons aged 76 and older. It is possible that cognitive impairment is a
      clinical feature of frailty and therefore should be included in the frailty
      definition.

PMID- 23970190
TI  - Laparoscopic and open subtotal colectomies compared in a high-volume laparoscopic
      center.

PMID- 23970191
TI  - HIF-1alpha is a crucial factor in the development of peritoneal dissemination via
      natural metastatic routes in scirrhous gastric cancer.
AB  - The molecular mechanisms underlying the peritoneal dissemination of gastric
      cancer remain unclear. Using in vivo metastatic models, this study attempted to
      clarify the role of hypoxia inducible factor (HIF)-1alpha in the development of
      peritoneal dissemination of gastric cancer. HIF-1alpha knockdown (KD) cells were
      established in the scirrhous gastric cancer cell line 58As9. Using KD and control
      (SC) cells, the presence of peritoneal dissemination was assessed in orthotopic
      implantation (o.i.) and intraperitoneal injection (i.p.) models. A series of in
      vitro analyses were also conducted. Finally, tumor angiogenesis was
      immunohistochemically analyzed. In the o.i. model, peritoneal dissemination was
      more frequently observed in the SC mice (93%) compared to the KD mice (13%)
      (P<0.001). In the i.p. model, peritoneal dissemination occurred at a high rate in
      both types of mice; however, a greater number of nodules was observed in the KD
      mice (P=0.017). The in vitro assays showed that HIF-1alpha exerts unfavorable
      effects on anoikis resistance and adhesion to extracellular matrix. Angiogenesis
      and vascular invasion were more aggressive in the SC gastric tumors. Vascular
      invasion was present in the intratumoral regions of the disseminated nodules in
      the SC o.i., but not the i.p., mice. HIF-1alpha was found to be crucial for the
      development of peritoneal dissemination in o.i. model, which mimics natural
      metastasis. In contrast, HIF-1alpha played an inhibitory role in suppressing
      peritoneal dissemination in the i.p. model. These results indicate that
      peritoneal dissemination in o.i. mice may not act through a seeding mechanism. An
      immunohistochemical analysis demonstrated HIF-1alpha-activated angiogenesis and
      vascular invasion in stomach tumors. Furthermore, the results showed that the
      disseminated nodules observed in SC o.i. mice were formed via extravasation of
      cancer cells. We provide a possible mechanism in which peritoneal dissemination
      of gastric cancer develops via a vascular network whereby HIF-1alpha activates
      tumor angiogenesis.

PMID- 23970192
TI  - The changing paradigm of the hand surgery technique article.

PMID- 23970193
TI  - Early active mobilization following UCL repair With Mitek bone anchor.
AB  - Ulnar collateral ligament (UCL) injuries of the thumb are common. Surgical repair
      is accepted as the treatment of choice for complete rupture of the ligament.
      Biomechanical studies have suggested that Mitek bone anchor repairs are
      potentially safe and strong enough to allow early controlled active mobilization.
      To date, there have been no studies to compare early active mobilization
      following Mitek bone anchor repair to standard postoperative rehabilitation
      involving thumb spica immobilization for the first 4 to 6 weeks. We performed a
      small pilot randomized control trial to assess the outcome of this new
      rehabilitation technique to that of standard immobilization following UCL repair
      with Mitek bone anchor. Our results show that on average early active
      mobilization leads to an earlier return to full hand function (6 vs. 8 wk) and an
      earlier return to work (7 vs. 11 wk). There is no difference in the final range
      of motion achieved. We suggest that Mitek bone anchor repairs for UCL ruptures
      are robust enough to allow early active mobilization and that a larger trial is
      warranted to assess whether early active mobilization is superior to standard
      rehabilitation. 

PMID- 23970194
TI  - The "double-barrel" knot: a new sliding knot for arthroscopic soft tissue
      fixation using single-pulley and double-pulley techniques.
AB  - The double-barrel knot is a new arthroscopic sliding knot for soft tissue
      reconstruction and repair procedures in arthroscopic and open shoulder surgery.
      The double-barrel knot is a modified sliding hitch, and is formed using 2 sutures
      from a single double-loaded anchor (single-pulley technique) or 2 sutures from 2
      adjacent anchors (double-pulley technique). This paper describes the method of
      double-barrel knot formation, and its variations; in addition, single-pulley and
      double-pulley techniques for anterior glenoid labral repair are presented. 

PMID- 23970195
TI  - Percutaneous fixation of hand fractures using locked K-wires: mechanical analysis
      and clinical application.
AB  - Closed percutaneous wire fixation of hand fractures frequently requires
      protection with external splintage. This splintage increases the risk of joint
      stiffness, prolongs recovery time, and increases therapy input. We have developed
      a method of linking external Kirschner wires (K-wires), using a metal clamp,
      after their insertion, so as to increase the security of fixation and facilitate
      postoperative mobilization. The mechanical properties of this method have been
      assessed in vitro and compared with conventionally fixed, unlinked, K-wires. We
      have been able to establish that the linked K-wire system is better able to
      resist loosening. This work proposes that linkage of K-wires permits omission of
      all additional external splintage, with no detriment to management. The technique
      has been applied in clinical cases over the past 8 years and results of
      treatments were evaluated mainly to detect unexpected complications. We report a
      low rate of complications and good results in terms of bone healing and recovery
      of function. 

PMID- 23970196
TI  - Free vascularized fibular transfer with langenskiold procedure for the treatment
      of congenital pseudarthrosis of the forearm.
AB  - Congenital pseudarthrosis of the radius or ulna is a rare entity. It is
      associated with neurofibromatosis, but occurs much less commonly than congenital
      pseudarthrosis of the tibia. Pseudarthrosis of the forearm can lead to pain,
      deformity, and limited forearm rotation. Nonsurgical management leads to poor
      results, as do surgical treatments such as open reduction internal fixation and
      conventional bone grafting. The transfer of a free vascularized fibula to the
      forearm pseudarthrosis has been more successful, and it is our preferred method
      of treatment for children with this condition. Because the transfer is often
      performed in young children, there is the potential for valgus deformity at the
      ankle after the fibula is removed. We describe here our technique for the
      transfer, including the technique for distal tibiofibular fusion (Langenskiold
      procedure) after removal of the fibular graft. In addition, we present the
      results of 5 patients who have undergone this combination of procedures for
      pseudarthrosis of the forearm at our institution. 

PMID- 23970197
TI  - Olecranon osteotomy fixation using a novel device: the olecranon sled.
AB  - A posterior approach to the elbow utilizing an olecranon osteotomy has been shown
      to provide excellent visualization of the distal humerus articular surface.
      However, many bony stabilization and fixation methods for the olecranon osteotomy
      are usually prominent, frequently symptomatic, and often require a second
      operation for removal. This paper evaluates the use of an innovative device, the
      olecranon sled, in fixation of olecranon osteotomies for exposure of intra
      articular distal humerus fractures and provides follow-up results. A
      retrospective review of all patients with intra-articular distal humerus fracture
      treated through an olecranon osteotomy approach and fixed with an olecranon sled,
      between September 2008 and December 2011 was conducted. Charts and radiographs
      were reviewed to determine olecranon union or nonunion, presence of symptomatic
      hardware, and need for secondary surgery to remove symptomatic olecranon
      fixation. Fourteen patients were included in the study. Average clinical follow
      up was 33.5 weeks (range, 6 to 118 wk). There were no olecranon nonunions. One
      patient underwent additional surgery for symptomatic hardware removal (7.1%). Two
      additional procedures were performed; 1 for revision open reduction and internal
      fixation of distal humerus fracture nonunion (7.1%) and 1 for release of elbow
      contracture (7.1%). Although follow-up is limited, the use of this device has
      been associated with excellent rates of olecranon union with a low rate of
      symptomatic hardware requiring removal. 

PMID- 23970198
TI  - T.A.C.' pin fixation for basal ulnar styloid fractures associated with distal
      radius fractures.
AB  - Distal radius fractures often accompany ulnar styloid fractures. As basal ulnar
      styloid fractures sometimes result in symptomatic nonunion causing distal
      radioulnar joint instability, surgical intervention should be considered as a
      method of treatment. However, conventional methods of internal fixation for ulnar
      styloid involving tension band wiring and pinning often causes irritation of
      hardware, and required further surgery. We performed T.A.C.' pin fixation for
      basal ulnar styloid fractures associated with distal radius fractures in 24
      patients. X-rays showed union at an average of 6.8 weeks postoperatively in all
      but 1 case, which resulted in asymptomatic fibrous nonunion. Irritation from the
      hardware was recognized in 3 cases, but soon disappeared after recutting or
      removal of the pin. At the final follow-up, no symptoms involving ulnar wrist
      pain or distal radioulnar instability were noted. T.A.C.' pin fixation for basal
      ulnar styloid is a useful method and rarely requires further surgery compared
      with conventional methods. 

PMID- 23970199
TI  - Correction of extra-articular distal radius malunions using an anatomic radial
      plate.
AB  - Malunion is a debilitating complication of a distal radius fracture. The malunion
      often requires a corrective osteotomy to restore the stability and joint
      congruity about the distal radius, a procedure which offers tremendous benefits
      in terms of pain, strength, and functionality. Here we describe a unique
      technique to address the malunion of an extra-articular distal radius fracture
      using a radial anatomic plate. This is a simple and reproducible method of
      fixation involving straightforward anatomy, which does not require excessive
      radiography, and which represents an excellent choice of fixation in the distal
      radius malunion. 

PMID- 23970200
TI  - Distal interphalangeal joint arthrodesis using nitinol intramedullary fixation
      implants: X-fuse implants for DIP arthrodesis.
AB  - Arthrodesis has been shown to be a successful operative procedure for the
      treatment of intractable pain, instability, and deformity of the distal
      interphalangeal joint of the fingers, and interphalangeal joint of the thumb.
      Multiple fixation techniques have been used in the past including Kirschner
      wires, tension bands, headless screws, or lag screws. Clinical results are
      generally acceptable, but complication rates have been reported to vary between
      10% and 20%. Complications include nonunion, pain, malunion, infection, nerve
      injury, and protruding hardware. The aim of this study is to describe an
      alternative technique for arthrodesis of the distal interphalangeal joint of the
      fingers or interphalangeal joint of the thumb using Nitinol implants for
      intramedullary fixation with a minimal complication rate. 

PMID- 23970201
TI  - Olecranon extrabursal endoscopic bursectomy.
AB  - Olecranon bursitis is a common clinical problem. It is often managed
      conservatively because of the high rates of wound complications with the
      conventional open surgical technique. Conventional olecranon bursoscopy utilizes
      an arthroscope and an arthroscopic shaver, removing the bursa from inside-out. We
      describe an extrabursal endoscopic technique where the bursa is not entered but
      excised in its entirety under endoscopic vision. A satisfactory view is obtained
      with less morbidity than the open method, while still avoiding a wound over the
      sensitive point of the olecranon. 

PMID- 23970202
TI  - Salter-Harris type II proximal humerus injuries: our experience with a new
      external fixator.
AB  - Proximal humeral fractures in the pediatric population are commonly treated
      conservatively. When there is an indication for surgery, percutaneous pinning is
      considered to be the elective choice. We report our experience with a new
      external fixator that reduces the risk of pin migration and permits an early
      rehabilitation. The range of motion was completely restored in all patients and
      no pain or discomfort was detected at follow-up. According to the literature, a
      small varus malunion at the first x-ray control can be tolerated in the pediatric
      population because of the remodeling ability of the bone. We conclude that this
      system provides a good stability and healing of Salter-Harris type II proximal
      humerus injuries. 

PMID- 23970203
TI  - Combined common extensor and supinator aponeurotomy for the treatment of lateral
      epicondylitis.
AB  - Pain at the lateral epicondyle and the extensor origin that is attributable to
      lateral epicondylitis can be successfully treated with a combined aponeurotomy of
      the supinator and the extensor muscles. This technique has been used at our
      institution for over 3 decades with good results. Aponeurotomy of the supinator
      decompresses the posterior interosseous nerve, whereas the extensor aponeurotomy
      relieves the stresses on the extensor carpi radialis brevis origin. We
      retrospectively reviewed a series of 56 patients clinically diagnosed with
      resistant lateral epicondylitis who underwent surgery by a single surgeon with
      our technique between 2002 and 2010. Patients experienced a subjective
      improvement in symptoms, visual analog pain score, and grip strength (Jamar II).
      Only 3% of patients experienced recurrence requiring further treatment. 

PMID- 23970204
TI  - Microfluidic traps for hard-wired operations on droplets.
AB  - We present microfluidic modules (traps) that allow us to lock, shift, dose and
      merge micro-aliquots of liquid precisely. The precision is hard-wired into the
      geometry of the device: small values of the capillary number guarantee
      reproducibility of operation over a range of rates of flow that need not be
      controlled precisely. The modules can be integrated into systems that perform
      complicated protocols on micro-droplets while not requiring precision in forcing
      the flow. 

PMID- 23970205
TI  - microRNA-155 regulates cell proliferation and invasion by targeting FOXO3a in
      glioma.
AB  - microRNAs (miRNAs) are short noncoding RNAs, which modulate the expression of
      numerous genes by targeting mRNAs. Numerous abnormal miRNA expression patterns
      are found in various human malignancies, and certain miRNAs act as oncogenes or
      tumor suppressors. microRNA-155 (miR-155) may not only function as an oncogene
      but also as a tumor suppressor in various types of cancer cells, such as
      melanoma. Although miR-155 has been found to be upregulated in glioma, its role
      has not yet been eludicated in glioma tumorigenesis. Based on the prediction of
      the target genes of miR-155, we hypothesized that there is a significant
      association between miR-155 and FOXO3a, a negative regulator of Akt signaling. In
      the present study, we found that FOXO3a expression was significantly
      downregulated and miR-155 was upregulated in a panel of glioma cells and tissue
      specimens. Furthermore, we demonstrated that miR-155 induced cell proliferation
      by inhibiting apoptosis and promoted the migration and invasiveness of glioma
      cells, while miR-155 had no effect on the cell cycle as determined by gain-of
      function and loss-of-function experiments. Moreover, we confirmed that miR-155
      downregulated the expression of FOXO3a by directly targeting its 3'-UTR. These
      findings indicate that miR-155 may function as an oncogene by targeting FOXO3a in
      the development and progression of glioma. 

PMID- 23970206
TI  - Evaluation of four tenofovir-containing regimens as first-line treatments in
      Cameroon and Senegal: the ANRS 12115 DAYANA Trial.
AB  - BACKGROUND: The aim of the present study was to determine appropriate tenofovir
      based regimens meriting evaluation in large-scale randomized trials among sub
      Saharan African patients. METHODS: This was a randomized open-label 96-week
      prospective pilot study evaluating four first-line regimens:
      tenofovir/emtricitabine/nevirapine (group 1), tenofovir/lopinavir/ritonavir
      (group 2), tenofovir/emtricitabine/zidovudine (group 3) and
      tenofovir/emtricitabine/efavirenz (group 4) in antiretroviral-naive, HIV-1
      infected patients in Senegal and Cameroon. The primary end point was defined as
      an HIV-1 RNA viral load <50 copies/ml (study detection limit) at week 16 in >=50%
      of patients using intention-to-treat analysis. RESULTS: At baseline, 119 patients
      included were 34% male, had a median plasma viral load of 5.4 log10 copies/ml and
      median CD4(+) T-cell count of 200 cells/mm(3) (range 53-358). The primary end
      point was achieved for groups 1, 3 and 4 (58% [n=31], 62% [n=29] and 53% [n=30],
      respectively), but not for group 2 (38% [n=29]). At week 96, undetectable HIV-1
      RNA had been achieved in 74% of patients in group 1, 38% in group 2, 72% in group
      3 and 73% in group 4. Patients with detectable HIV-1 RNA at week 16 were more
      likely to have baseline HIV-1 RNA>=100,000 copies/ml (adjusted OR 5.56, 95% CI
      1.72, 16.67). HIV mutations associated with protease inhibitor resistance emerged
      in three patients, all of whom were in group 2. Anaemia occurred in two group 3
      patients and was the only serious treatment-related adverse event. CONCLUSIONS:
      Three efficient and safe tenofovir-based triple regimens were identified; the two
      drug regimen (tenofovir/lopinavir/ritonavir) did not achieve the protocol-defined
      virological threshold of efficacy.

PMID- 23970207
TI  - The new 6-unit individualized curriculum for pediatric residents: the perspective
      of neonatology fellowship program directors.
AB  - OBJECTIVE: Starting in 2013, all pediatric residents entering fellowship must be
      provided six educational units whose structure is to be determined by their
      individual career plans. We sought to determine whether (1) neonatology
      fellowship program directors (PDs) consistently identify certain weaknesses among
      incoming fellows and (2) neonatology fellowship PDs agree on the most beneficial
      activities in which pediatric residents should participate to improve preparation
      for entry into neonatology fellowships. STUDY DESIGN: We sent a 21-question
      survey focused on the structure and implementation of the 6-unit curriculum to
      all members of the Organization of Neonatology Training Program Directors.
      RESULTS: Sixty-seven percent of PDs responded. Seventy-five percent cited
      insufficient procedural skills as the primary weakness of incoming fellows. More
      than 80% rated additional training in clinical neonatology, including procedural
      and resuscitation training, as 'beneficial' or 'highly beneficial'. In contrast,
      fewer than 40% of PDs gave the same positive ratings to activities broadly
      focused on scholarship. CONCLUSIONS: The results of the survey may help guide
      pediatric residency programs as they undertake development of these new
      curricular initiatives for individual residents entering neonatology.

PMID- 23970208
TI  - William A Silverman lecture.
AB  - This is the text of the William A Silverman lecture given by Dr David K Stevenson
      at the Pediatric Academic Societies Annual Meeting in Washington, DC, May 4-7,
      2013. 

PMID- 23970209
TI  - Superiority of targeted neonatal echocardiography for umbilical venous catheter
      tip localization: accuracy of a clinician performance model.
AB  - OBJECTIVES: To compare targeted neonatal echocardiography (TnECHO) and antero
      posterior (AP) chest radiographs in the localization of the umbilical venous
      catheter (UVC) tip and to determine the accuracy of UVC tip localization by
      TnECHO when performed by a trained cohort of pediatric housestaff physicians.
      STUDY DESIGN: Prospective, observational study of consecutive neonates requiring
      UVC insertion, in a tertiary care center, in an 18-month period. Chest
      radiographs reporting optimal position of the UVC tip were compared with the
      TnECHO results of the pediatric cardiologist. The latter was also compared with
      the results of TnECHO performed by the pediatric housestaff physicians. RESULT:
      Thirty neonates with birth weight ranging between 270 and 4490 g and gestational
      age ranging between 24 and 44 weeks were enrolled. Nine patients (27%) required
      UVC tip repositioning as the cardiologist performed TnECHO revealed sub-optimal
      tip position despite optimal position on chest radiography. Among them, four had
      the UVC tip in the right atrium and five in the left atrium. Compared with the
      cardiologist, the housestaff physicians had reported TnECHO with a high-accuracy
      rate (area under the receiver operating characteristic curve=0.81). CONCLUSION:
      TnECHO is superior to chest radiography for identifying malpositioned catheters.
      TnECHO performed by pediatric housestaff physicians with basic training,
      demonstrated high-accuracy rates.

PMID- 23970210
TI  - Does it matter what children eat?

PMID- 23970211
TI  - Human milk and the premature infant.
AB  - Human milk is the preferred feeding for both term and preterm infants. While
      being considered optimal for term infants, human milk, even from mothers
      delivering preterm infants, is lacking in protein, energy, sodium, calcium, and
      phosphorus, resulting in poorer growth and nutrient deficiencies when compared to
      formulas designed for these high-risk infants. Further, the lack of growth is
      associated with long-term adverse consequences. Since human milk has unique
      properties in promoting gastrointestinal maturation and immunological benefits,
      it is prudent to implement strategies to fortify it appropriately to realize its
      benefits which include reduced rates of necrotizing enterocolitis, fewer episodes
      of sepsis and urinary tract infections, and improved visual and neurocognitive
      development. Donor human milk is being widely used when mothers' own milk is not
      available or is in short supply. While it retains some of the biological
      properties and clinical benefits of mothers' own milk, it requires additional
      care in fortification, especially if the donor milk is from a pool of term human
      milk. As nutritional strategies improve, the ultimate goal is to minimize
      extrauterine growth restriction and promote appropriate growth after regaining
      birth weight. 

PMID- 23970212
TI  - Feeding patterns during the first 2 years and health outcome.
AB  - Low-birth-weight infants, in particular those with birth weights <1,500 g,
      benefit from fortified breast milk. Low protein intake is critical, because it is
      limiting growth. Long-term health outcomes in small-for-gestational-age infants
      from developing countries in relation to their early nutrition still need to be
      evaluated in controlled trials. Term infants both in developing and developed
      countries also benefit from exclusive breastfeeding: an analysis of a large
      dataset of surveys from 20 developing countries (168,000 infants and small
      children from the Demographic Health Survey, United States Agency for
      International Development) indicates that exclusive breastfeeding until 6 months
      is associated with significantly higher weight, length, and lower probability of
      stunting, wasting, and infections. Nine out of 10 infants still receive breast
      milk between 6 and 12 months and probability of infections tends to be lower if
      breastfeeding is continued during that age range. Between 12 and 24 months, when
      stunting and wasting rates are already high, 7 out of 10 infants still receive
      breast milk. No associations of feeding patterns with disease outcome can be
      found. Effectiveness trials of complementary feeding strategies in food-insecure
      countries are urgently needed. Follow-up until 10 years in a developed country
      now indicates that an infant population at risk for allergic diseases benefits
      both from breastfeeding and the use of hypoallergenic formula during the first 4
      months of life, when compared to cow's milk-based formula: both the cumulative
      incidences of atopic disease and all allergic diseases are significantly lower. 

PMID- 23970213
TI  - Lessons from the feeding infants and toddlers study in North America: what
      children eat, and implications for obesity prevention.
AB  - The latest exhaustive survey of dietary patterns in infants from the Feeding
      Infants and Toddlers Study (FITS) in North America documents and quantifies
      current trends in infant feeding. These include higher than generally recommended
      energy, protein, and saturated fat intakes. The majority of infants are bottle
      fed at some point in their first year of life, and their weaning diet often
      includes low intakes of fruits and vegetables, with high starchy, rather than
      green or yellow, vegetables. Early introduction of solids, use of cow's milk
      prior to 1 year of age, and high juice intake in the first 2 years - all less
      desirable diet practices - are improving, but are still prevalent. More
      preschoolers are likely to get sweets or sweetened beverages than a serving of
      fruit or a vegetable on a given day. These food intake patterns mimic the adult
      American diet and are associated with an increased risk of obesity in childhood
      and later life. But more importantly, these patterns appear to be set as early as
      18 months of age, and by 20 months of age, they mimic the adult diet. Despite
      increase in total energy intake, and greater variety of foods, the basic
      characteristics of macronutrient intake distribution and food group contribution
      of energy to the diet before 2 years of age remain remarkably stable and similar
      to the family table. Obesity prevention needs to include specific targets in
      terms of breastfeeding and adequate formula feeding, as well as appropriate
      introduction of weaning foods with goals of changing the inadequate patterns
      documented in the FITS. These interventions will also require addressing parent
      and caregiver behaviors, including attending to hunger satiety cues (responsive
      feeding), and shaping early food preferences. This needs to be done starting at
      birth, in the first months of life. Early intervention offers a unique and
      potentially efficacious opportunity to shape the future dietary patterns of the
      next generation. 

PMID- 23970214
TI  - Influences on children's dietary behavior, and innovative attempts to change it.
AB  - Fruit and vegetable (FV) intake may protect against several chronic diseases, and
      the preferences and habits in relation to FV intake appear to form in early
      childhood. Child FV intake reflects many influences from multiple levels (e.g.
      internal to the child, family, school, and neighborhood). We have documented
      influences at each of these levels, but more definitive research in longitudinal
      samples remains to be conducted. Even though validated comprehensive models of
      influences on child FV intake in longitudinal studies are not available to guide
      intervention design for children of different ages, there has been an urgency to
      initiate chronic disease prevention interventions to mitigate the substantial
      health consequences. Effective interventions use known behavior change procedures
      to change the influences on FV intake enough to change the behavior, but few such
      interventions have demonstrated effectiveness at meaningful levels. Innovative
      methods need to be explored. Videogames for Health offer a medium that is
      attractive to children and shows promising results, especially for dietary
      behavior change. Exciting additional research is needed to clarify possible
      bidirectional influences between the environmental and individual influences on
      child intake with possible age-related differences in influence and in the
      optimal design of video games for dietary change. 

PMID- 23970215
TI  - FITC-quencher based caspase 3-activatable nanoprobes for effectively sensing
      caspase 3 in vitro and in cells.
AB  - By employing fluorescence resonance energy transfer (FRET) quenching, we
      rationally designed two new FITC-quencher based nanoprobes for effectively
      sensing caspase 3 (Casp3) in vitro and in cells. Our nanoprobes hold promise for
      assessing the chemotherapeutic effect of cancer treatment. 

PMID- 23970216
TI  - Extending the tissue penetration capability of conventional photosensitisers: a
      carbon quantum dot-protoporphyrin IX conjugate for use in two-photon excited
      photodynamic therapy.
AB  - A carbon quantum dot (CQD)-protoporphyrin (IX) sensitisier conjugate was designed
      to exploit the large two-photon absorption cross section of CQDs and enable the
      indirect excitation of the sensitiser with 800 nm irradiation via FRET. 

PMID- 23970217
TI  - Nursing offices.

PMID- 23970218
TI  - Comparison between the International Physical Activity Questionnaire and the
      American College of Sports Medicine/American Heart Association criteria to
      classify the physical activity profile in adults.
AB  - OBJECTIVE: the study aims to evaluate the reproducibility between the
      International Physical Activity Questionnaire and the American College of Sports
      Medicine/American Heart Association criteria to classify the physical activity
      profile in an adult population living in Ribeirao Preto, SP, Brazil. METHODS:
      population-based cross-sectional study, including 930 adults of both genders. The
      reliability was evaluated by Kappa statistics, estimated according to socio
      demographic strata. RESULTS: the kappa estimates showed good agreement between
      the two criteria in all strata. However, higher prevalence of "actives" was found
      by using the American College of Sports Medicine/American Heart Association.
      CONCLUSIONS: although the estimates have indicated good agreement, the findings
      suggest caution in choosing the criteria to classify physical activity profile
      mainly when "walking" is the main modality of physical activity.

PMID- 23970219
TI  - Validation of the process criteria for assessment of a hospital nursing service.
AB  - OBJECTIVE: to validate an instrument containing process criteria for assessment
      of a hospital nursing service based on the National Accreditation Organization
      program. METHOD: a descriptive, quantitative methodological study performed in
      stages. An instrument constructed with 69 process criteria was assessed by 49
      nurses from accredited hospitals in 2009, according to a Likert scale, and
      validated by 16 judges through Delphi rounds in 2010. RESULT: the original
      instrument assessed by nurses with 69 process criteria was judged by the degree
      of importance, and changed to 39 criteria. In the first Delphi round, the 39
      criteria reached consensus among the 19 judges, with a medium reliability by
      Cronbach's alpha. In the second round, 40 converging criteria were validated by
      16 judges, with high reliability. The criteria addressed management, costs,
      teaching, education, indicators, protocols, human resources, communication, among
      others. CONCLUSION: the 40 process criteria formed a validated instrument to
      assess the hospital nursing service which, when measured, can better direct
      interventions by nurses in reaching and strengthening outcomes.

PMID- 23970220
TI  - Translation and validation of the parent-adolescent communication scale:
      technology for DST/HIV prevention.
AB  - OBJECTIVES: accomplishment of the transcultural adaptation of the Parent
      adolescent Communication Scale, which evaluates the frequency of communication
      between parents and children concerning the subjects related to sex, condom, DST,
      HIV and pregnancy. METHOD: Methodological research of quantitative approach,
      accomplished with 313 adolescent pupils of the feminine sex in the 14 to 18 year
      age group in Fortaleza-CE. The content validity was carried through by means of
      the initial translation, back translation, pre-final version and final version,
      being analyzed by a committee of specialists; the reliability was verified by the
      Cronbach's Alpha and ascertained by testing the hypotheses and test-retest within
      five weeks. The scale was applied via computer in the online modality in the
      period November/2010 to January/2011. RESULTS: The version of the instrument in
      Portuguese presented an Alpha of 0.86 regarding the validity of the structure,
      was partially verified since the testing of the hypotheses of the contracted
      group was not confirmed. CONCLUSION: The version of the instrument adapted for
      Portuguese is considered valid and reliable in the study sample.

PMID- 23970221
TI  - Quality of life and burden in carers for persons with chronic obstructive
      pulmonary disease receiving oxygen therapy.
AB  - OBJECTIVE: to assess the quality of life and burden of caregivers to Chronic
      Obstructive Pulmonary Disease patients on Long-Term Oxygen Therapy and to
      investigate the factors influencing this burden. METHOD: this is an analytical,
      cross-sectional study of 80 persons with Chronic Obstructive Pulmonary Disease on
      Long-Term Oxygen Therapy who used the specialized outpatient center of the
      Federal University of Sao Paulo, and their carers. The following instruments were
      used: Medical Outcomes Studies 36 (SF-36), Caregiver Burden Scale (CBS) and the
      Katz Index, along with socio-demographic and clinical variables. RESULTS: the
      most compromised scores on the carers' quality of life questionnaire were for
      Vitality and Mental Health. On the Caregiver Burden Scale, the domain which
      created the greatest burden for carers was the Environment. With the exception of
      Emotional Involvement, all the domains of quality of life were affected
      negatively by the domains of caregiver burden. CONCLUSION: it was shown that
      carers' quality of life was compromised and that they were overburdened with care
      tasks, confirming that assisting persons with Chronic Obstructive Pulmonary
      Disease is an important element in carers' quality of life.

PMID- 23970222
TI  - Quality of life of victims of traumatic brain injury six months after the trauma.
AB  - OBJECTIVE: to describe the quality of life of victims of traumatic brain injury
      six months after the event and to show the relationship between the results
      observed and the clinical, sociodemographic and return to productivity data.
      METHOD: data were analyzed from 47 victims assisted in a trauma reference
      hospital in the municipality of Aracaju and monitored in an outpatient
      neurosurgery clinic. The data were obtained through analysis of the patient
      records and structured interviews, with the application of the World Health
      Organization Quality of Life, brief version, questionnaire. RESULTS: the victims
      presented positive perceptions of their quality of life, and the physical domain
      presented the highest mean value (68.4+/-22.9). Among the sociodemographic
      characteristics, a statistically significant correlation was found between
      marital status and the psychological domain. However, the return to productivity
      was related to all the domains. CONCLUSION: the return to productivity was an
      important factor for the quality of life of the victims of traumatic brain injury
      and should direct the public policies in promoting the health of these victims.

PMID- 23970223
TI  - Overload of families taking care of elderly people with Alzheimer's Disease: a
      comparative study.
AB  - OBJECTIVE: to compare the overload of the main and secondary family carers of
      patients with Alzheimer's Disease, and identify which dimension generates most
      impact. METHOD: a comparative study conducted in the city of Maringa, State of
      Parana, with 20 primary carers of elderly patients with Alzheimer's Disease and
      20 secondary caregivers. The data was collected in May and June 2012, using the
      Scale for Assessment of Overload of Members of Psychiatric Patients' Families
      (FBIS-BR), and the results were analysed using the Mann-Whitney test and analysis
      of variance. RESULTS: the global objective overload, and also in each subscale,
      was significantly greater in the group of main caregivers; the subjective
      overload showed no difference between the groups. Comparing the subscales, the
      routine assistance provided to the patient had greater influence on objective
      overload in both groups, and the concern with the elderly patient was the
      dimension that had most influence on the subjective overload of main caregivers
      and also of secondary caregivers. CONCLUSION: the differences in overload between
      the different groups reinforces the need for planning of health care actions for
      each type of caregiver, seeking to reduce these differences.

PMID- 23970225
TI  - Prevalence of frailty syndrome in old people in a hospital institution.
AB  - OBJECTIVE: to measure the prevalence of frailty syndrome in elderly inpatients in
      a hospital institution. METHODS: cross-sectional study using a sample of 99
      subjects aged 65 or older, hospitalized in the month of November/2010 in Sao
      Vicente de Paulo Hospital in Passo Fundo, Rio Grande do Sul state (RS). Data were
      collected regarding the phenotype of the frailty, along with social and
      demographic, clinical and anthropometric information. RESULTS: the mean age was
      74.5+/-6.8 years and 50 (50.5%) were women. 4% were classified as non-frail, 49
      (49.5%) as pre-frail and 46 (46.5%) as frail. No statistically significant
      factors were identified that were associated with frailty. CONCLUSIONS: as was
      expected, the prevalence in this population was found to be high compared to
      other studies that focused on the community. It is believed that early detection
      and interdisciplinary intervention can prevent the progression of the condition
      and reduce the incidence of complications and hospitalization.

PMID- 23970224
TI  - Communication between the elderly person and the family health team: is there
      integrality?
AB  - OBJECTIVE: to verify the forms of communication used in four Primary Health Units
      with Family Health Program teams in Porto Feliz, Sao Paulo, and how they impact
      in the care and control of the health of elderly people. METHOD: this qualitative
      study sought to capture the communication between elderly people and healthcare
      professionals. Interviews were conducted with 20 elderly people of both sexes.
      RESULTS: from the discourses and observations, assertive communication and
      blocked communication emerged as the central analysis themes, the verbal and
      nonverbal elements of which, unveiled subjectivity of the communication process,
      of the local culture and of the psychosocial factors positively and negatively
      contributing to the healthcare for elderly people. The nursing teams of the
      Family Health Strategy showed forms of communication that favored the adherence
      of the elderly people to the care and control of their health. Negatives aspects
      did not have completely prejudicial consequences, however, should be avoided, in
      order to facilitate integral care to elderly people. CONCLUSION: it is worth
      reinforcing the need for improvement of the nursing team and other healthcare
      professionals regarding health communication as an innovative technology,
      bringing credibility to the health promotion and prevention programs with elderly
      users.

PMID- 23970227
TI  - Vulnerability to sexually transmitted infections in women who sell sex on the
      route of prostitution and sex tourism in central Brazil.
AB  - OBJECTIVE: to investigate knowledge on sexually transmitted diseases (STDs), STD
      related risk behaviors, and signs/symptoms of STDs among female sex workers
      (FSWs). METHODS: a cross-sectional study was conducted with a probabilistic
      sample comprising 395 women recruited using a respondent-driven sampling method
      between 2009 and 2010. The data were collected during face-to-face interviews.
      RESULTS: most of the participants were young adults, had a low educational level,
      and had poor knowledge on the transmission paths of the human immunodeficiency
      virus (HIV). Over one-third of the participants were not able to describe the
      signs/symptoms of STDs. The prevalence rates of vaginal discharge and
      wounds/ulcers were 49.0% and 8.6%, respectively, but 41.7% of the women had not
      sought treatment. CONCLUSION: the results indicate the need for public health
      policies focusing on the control and prevention of STDs in this population,
      especially for the FSWs who are active in an important prostitution and sex
      tourism route in central Brazil.

PMID- 23970226
TI  - The experience of women with abortion during adolescence as demanded by their
      mothers.
AB  - OBJECTIVE: to understand the experience of women who induced an abortion during
      adolescence as demanded by their mothers. METHOD: qualitative study with a social
      phenomenology approach conducted in 2010 with three women through interviews with
      open questions. RESULTS: the participants tried to hide their pregnancies from
      their mothers and when the mothers found out about the pregnancies they decide to
      interrupt it, demanding that their daughters have an abortion, which was
      performed in an unsafe manner, regardless of the adolescents' desire. After the
      abortion, the adolescents experienced suffering, guilt, and regret for not having
      fought against their mothers' decisions. These women expect to be autonomous to
      make their own decisions, take care of their own health and become pregnant
      again. CONCLUSION: the study evidenced the decision for an abortion was centered
      on the adolescents' mothers, a result that deserves to be further explored in
      future research deepening the relationship established between daughter and
      mother in the situation of an induced abortion. We suggest the creation of
      opportunities for the triad of health professional/adolescent/family to dialogue,
      especially the mother, who in the context of family relations, can help the
      daughter to safely deal with an early pregnancy and prevent it instead of
      influencing the adolescent to induce an abortion.

PMID- 23970228
TI  - The motherhood experience in the context of social vulnerability: a comprehensive
      approach to social phenomenology.
AB  - OBJECTIVE: to understand the future expectations and experience of vulnerable
      mothers from pregnancy to their child's early years. METHODS: this qualitative
      study used the social phenomenology of Alfred Schutz as a framework. From January
      to April 2011, nine mothers from the 2009 program "Chile Grows with You" were
      interviewed at health centers in an urban Santiago de Chile community. RESULTS:
      analysis of the "lived type" led to an understanding of the mothers' real-world
      experience. Unexpected pregnancies in extremely vulnerable mothers are associated
      with feelings of hopelessness then resignation. There is no plan for the future;
      the mother lives in the present with great uncertainty. CONCLUSIONS: from the
      mothers' stories, significant patterns were identified in their experiences,
      yielding insights into society from these women's perspectives. For humanized,
      comprehensive nursing care, this expertise directs interventions designed to
      overcome despair in women excluded because of their invisibility and poverty.

PMID- 23970229
TI  - Factors associated to the imposition of types of violence against women informed
      in sentry services.
AB  - OBJECTIVE: to identify the prevalence and the factors associated to the
      imposition of the different types of violence against women informed in sentry
      services. METHOD: transversal study accomplished through 939 notification forms
      of cases of violence against women, referring to the three years from 2006 to
      2008 in Fortaleza, Ceara. Univariate and multiple analyses by logistic regression
      were realized. RESULT: the results showed a positive association between the
      imposition of types of violence against women with a schooling varying from
      illiterate to basic education and the aggression which had occurred other times.
      CONCLUSION: this knowledge contributes to the delineation of specific actions
      that aim at facing this problem, as well as generates subsidies for adequate
      attendance proposals and guidance for the victims who call on health services.

PMID- 23970230
TI  - Knowledge of users of low-dose oral combined contraceptives about the method.
AB  - OBJECTIVES: to identify the knowledge of users of combined oral contraceptive
      about correct use, side effects and complications; to verify the correlation
      between knowledge about the method with age, education, family income and time of
      use. METHOD: cross-sectional study performed in Fortaleza, Ceara, Brazil, from
      March to July 2010, with 294 women. Data were collected through interviews.
      RESULTS: 75% had substantial knowledge about the proper use and side effects and
      no knowledge about complications. The higher the educational level and family
      income, the higher the women's knowledge about the correct use of the method.
      Positive correlation suggests that women who used the method for longer knew more
      about its side effects. CONCLUSION: there are knowledge gaps about the method,
      which are influenced by socioeconomic variables and use time.

PMID- 23970231
TI  - Burden, coping, physical symptoms and psychological morbidity in caregivers of
      functionally dependent family members.
AB  - OBJECTIVES: this study assessed burden, coping, physical symptoms and
      psychological morbidity in caregivers of functionally dependent family members.
      METHODS: fifty family caregivers completed self-reported measures of burden,
      physical symptoms, psychological morbidity and coping strategies. RESULTS: there
      was a significant negative correlation between coping strategies and the
      different clinical variables, as well as a significant positive correlation
      between coping strategies and duration of care. It appears that the stronger bond
      between caregiver and family member leads to a poorer use of adaptive coping
      strategies. It also appears that the deterioration of the relationship between
      them and the lower perceived self-efficacy are more prominent in caregivers of
      family members with cognitive impairment, indicating that caregivers with family
      members without cognitive impairment face fewer difficulties. CONCLUSION: these
      results emphasize the need for interventions to include coping strategies, since
      they are important in reducing caregivers' burden, psychological morbidity and
      physical symptoms.

PMID- 23970232
TI  - Alcohol consumption and risky sexual practices: the pattern of nursing students
      from the Spanish University.
AB  - OBJECTIVE: to determine the prevalence of substance abuse and unsafe sexual
      practices and to analyze the relationship between them, in nursing students at
      the University of Seville. METHOD: quantitative methodological approach with a
      descriptive cross-sectional design. The population was composed of first year
      nursing students in the University of Seville, during the academic year 2010-2011
      (N=510), with consecutive opportunistic sampling composed of students who
      attended class on the scheduled day (n=291). RESULTS: a high prevalence of
      alcohol consumption, and increased likelihood of not using protective measures
      during sexual practices when alcohol had been consumed, was present. CONCLUSION:
      these findings are consistent with those obtained in the same population in
      Brazil, and highlight the need to strengthen in the nursing curriculum, the
      transverse axis related to the prevention of substance abuse, especially alcohol.

PMID- 23970233
TI  - Consumption of psychiatric drugs by patients of medical and surgical clinics in a
      general hospital.
AB  - PURPOSES: to identify the prevalence of the use of psychiatric drugs among
      patients admitted to medical and surgical clinics of a general hospital, and also
      the factors related to the consumption of this type of medication. METHOD: this
      is a transversal, descriptive, correlational study with quantitative analysis.
      For the collection of data, there was use of structured interviews and also
      reference to medical files. RESULTS: there was confirmation of a high prevalence
      of users of psychiatric drugs, which was associated to the female sex, to people
      who do not practice Roman Catholicism, and admittance to the clinic not covered
      by the Single Health System (Sistema Unico de Saude - SUS), as well as the
      presence of common mental disorders. Benzodiazepine drugs were the most commonly
      used psychiatric drugs. Among the total number of users, there has been the
      identification of patients who were not aware that they were receiving such
      medication. Doctors who are not psychiatrists were responsible for most
      prescriptions of psychiatric drugs. CONCLUSIONS: this signals the need to prepare
      health professionals to deal with psychological and social problems commonly
      found in clinical practice, in order to promote the rational use of psychiatric
      drugs.

PMID- 23970234
TI  - Experiences from families of children with cerebral paralysis in context of
      social vulnerability.
AB  - OBJECTIVE: to describe and to analyze the experience from families of children
      with cerebral paralysis living under circumstances of social vulnerability.
      METHOD: six resident families in area with this characteristic were interviewed.
      It was opted to use the Symbolic Interactionism as theoretic reference and the
      Thematic Content Analysis of Bardin as analysis method for the data. RESULT: the
      experience of such families is represented in the subjects: Reorganizing the
      Life, with the categories "Discovering the way" and "Accommodating the routine",
      and Stopping a Constant Fight with the categories: "Primary Carer being
      overcharged", "Coexisting with the preconception", "Having locomotion difficulty"
      and "Living with financial difficulties". CONCLUSION: the social vulnerability
      influences how the family bears the chronic condition. Professionals and
      strategies of public health are a power to minimize impacts including those
      related to the family budget, but they have not been effective. They need to be
      sensitized to become supporting resources, to offer and to guide the access to
      the support networks and to spur the social service in action when necessary.
      This study adds knowledge to the already existing by pointing out peculiarities
      of the family experience in situations regarding two variables of difficult
      handling: chronicity and social vulnerability, evidencing the role of the
      professional in search of the solution for the confrontation of demands and
      sufferings together with the family.

PMID- 23970235
TI  - Maternal ability to take care of children exposed to HIV.
AB  - OBJECTIVE: to assess the ability of mothers to take care of children exposed to
      HIV, using the Assessment Scale of Care Skills for Children Exposed to HIV at
      Birth and to check the association between the scale dimensions and maternal
      characteristics. METHOD: this cross-sectional study involved 62 HIV+ mothers
      whose children of up to one year old had been exposed to the virus at birth. The
      Assessment Scale of Care Skills for Children Exposed to HIV at Birth consists of
      52 items and five dimensions, indicating high, moderate or low care ability.
      RESULTS: 72.7% of the mothers appropriately offered zidovudine syrup; 86.0% were
      highly skilled to prepare and administer milk formula; 44.4% were moderately able
      to prepare and administer complementary feeding; 76.5% revealed high ability to
      administer prophylactic treatment against pneumonia and 95.3% demonstrated high
      abilities for clinical monitoring and immunization. Significant associations were
      found between some maternal variables and the scale dimensions. CONCLUSION: the
      scale permits the assessment of maternal care delivery to these children and the
      accomplishment of specific child health interventions.

PMID- 23970236
TI  - Changes in the frequency of food intake among children and teenagers: monitoring
      in a reference service.
AB  - PURPOSE: to identify changes in the food intake patterns among overweight
      children and teenagers, treated at a reference medical centre. METHOD: the method
      used is that of a cohort study, between April 2010 and April 2011. A total of 109
      children and teenagers, either obese or overweight, took part in the study. The
      population was divided into two subgroups depending on the permanence period
      (more than 6 months, and less than 6 months off the treatment). The chi-square
      test and logistic regression were carried out. RESULTS: the group which had been
      longer off the treatment tended to consume more soft drinks, pasta and fried
      foods, and less fruit and vegetables. The group with less time showed an
      improvement, with a reduction of consumption of soft drinks and other goodies.
      There was confirmation of an increased risk for consumption of soft drinks, pasta
      and goodies in general, as also detachment from the treatment in adolescence.
      CONCLUSIONS: The group with a longer period of monitoring has had a positive
      change in food intake frequency. The main contribution made by this study is that
      of showing that multiprofessional treatment, including some nursing care, is
      efficient in progressively changing the food intake of children and adolescents
      who are overweight.

PMID- 23970237
TI  - Routine healthcare for families in transition after a natural disaster.
AB  - OBJECTIVE: to present the healthcare routines of families in transition after
      natural disasters based on the Family Routines and Rituals theoretical framework.
      METHOD: this qualitative study of multiple cases was developed based on six rural
      families in southern Brazil, 2 years after a natural disaster. The data were
      collected through participant observation, interviews, narratives, genograms,
      ecomaps, and routine calendars, and a narrative analysis was conducted. RESULTS:
      families showed notable episodes of illness that required professional assistance
      during post-disaster care, daily routine care, and other routines associated with
      healthcare services. CONCLUSION: these results reinforce the need for nurses to
      attend to family experiences during transitions after natural disasters and to
      prepare for the changes and needs with regard to healthcare and its promotion.

PMID- 23970238
TI  - Continuing education in the family health strategy: rethinking educational
      groups.
AB  - OBJECTIVE: to analyze the experience of the family health team in resignifying
      the way to develop educational groups. METHOD: groups of discussion, with twenty
      six biweekly group meetings conducted, with an average of fifteen professionals
      from the family health team, during the year 2009. The empirical material
      consisted of the transcription of the groups, on which thematic analysis was
      performed. RESULTS: two themes were developed and explored from the collective
      discussions with the team: "The experience and coordination of the groups" and
      "The work process and educational groups in a service-school". CONCLUSIONS:
      continuing Education in Health developed with the team, not only permitted
      learning about the educational groups that comprised the population, but also
      contributed to the team's analysis of its own relationships and its work process
      that is traversed by institutions. This study contributed to the advancement of
      scientific knowledge about the process of continuing health education as well as
      educational groups with the population. Also noteworthy is the research design
      used, providing reflexivity and critical analysis on the part of the team about
      the group process experienced in the meetings, appropriating knowledge in a
      meaningful and transformative manner.

PMID- 23970239
TI  - Public health emergency: social representations among managers of a university
      hospital.
AB  - AIM: to comprehend the social representations of public health emergencies among
      managers who experienced the Influenza A (H1N1) Pandemic of 2009. METHOD: a
      qualitative case study, with its theoretical and methodological framework based
      on the Theory of Social Representations. The data was obtained through the
      techniques of free association and semi-structured interviews, applied
      individually to managers who worked in different positions of the hierarchical
      management structure of the institution during the pandemic emergency, a total of
      30 participants. RESULTS: thematic content analysis resulted in the following
      categories: vulnerability, health protection, neglect - gray areas of the public
      sphere, and integrality. The social representations of public health emergencies
      attest to continuities that transit the overvalorization of negative discourses
      linked to the health/education public space, naturalization of the substantial
      character of the epidemic, and normative managerial action. However, the defense
      of ongoing education as a necessity associated with emergency management revealed
      possibilities for change in the technical-scientific perception of the
      management. CONCLUSIONS: to understand healthcare/nursing workers as political
      beings, assuming responsibilities in the areas of the macro and micro policies of
      the State, the university hospitals and the work teams, is a pathway that is
      emerging for the management of emergencies.

PMID- 23970241
TI  - Maternal atazanavir usage in HIV-infected pregnant women and the risk of maternal
      and neonatal hyperbilirubinemia.

PMID- 23970242
TI  - A proteorhodopsin-based biohybrid light-powering pH sensor.
AB  - The biohybrid sensor is an emerging technique for multi-functional detection that
      utilizes the instinctive responses or interactions of biomolecules. We develop a
      biohybrid pH sensor by taking advantage of the pH-dependent photoelectric
      characteristics of proteorhodopsin (pR). The transient absorption kinetics study
      indicates that the photoelectric behavior of pR is attributed to the varying
      lifetime of the M intermediate at different environmental pH values. This pR
      based biohybrid light-powering sensor with microfluidic design can achieve real
      time pH detection with quick response and high sensitivity. The results of this
      work would shed light on pR and its potential applications. 

PMID- 23970243
TI  - The end of pass/fail grades?

PMID- 23970244
TI  - A diagnostic revolution.

PMID- 23970245
TI  - [Breast-preserving surgery--always the right choice?].

PMID- 23970246
TI  - [Perhaps guideline enthusiasts are needed?].

PMID- 23970247
TI  - [Fundamentalism or best practice?].

PMID- 23970248
TI  - [V. Bruun Wyller replies].

PMID- 23970249
TI  - [Aminoglycosides in severe sepsis].

PMID- 23970250
TI  - [Aminoglycosides can reduce the risk].

PMID- 23970253
TI  - [Wrong etymology].

PMID- 23970252
TI  - [J.H. Laake & I. Nordoy replies].

PMID- 23970256
TI  - [Ritual circumcision in the global world].

PMID- 23970258
TI  - [The information about mammography screening is not neutral].

PMID- 23970259
TI  - [Increased understanding is the key in the fight against genital mutilation].

PMID- 23970271
TI  - [Breast cancer surgery in Norway 1986-2009].
AB  - BACKGROUND: Studies have revealed variations in breast cancer survival between
      different counties in Norway. This study describes trends in surgical treatment
      of ductal carcinoma in situ (DCIS) and breast cancer in Norway, over time and by
      county. MATERIAL AND METHOD: Information about surgical treatment, age and county
      for 3,915 women with DCIS and for 54,732 women with breast cancer, diagnosed in
      the periods 1995-2009 and 1986-2009 respectively, was provided from the incidence
      database at the Cancer Registry of Norway. RESULTS: In the period 1995-97, 3.0 in
      100,000 women with DCIS had breast conserving treatment (BCT), while 5.0 in
      100,000 had mastectomy. In 2004-06 the rates were 8.6 and 4.2, respectively. In
      1995-97, 18.7 in 100,000 women with breast cancer had BCT, while 77.3 in 100,000
      had mastectomy. In 2004-06 the rates were 57.9 and 50.8, respectively. The
      percentage of women with DCIS or breast cancer who were treated with BCT was
      lower in 2007-09 in all counties than in 2004-06. For 2007-09 the percentage of
      women with DCIS who were treated with BCT varied by county from 39% to 75%. For
      breast cancer the percentage varied from 33% to 67%. INTERPRETATION: The number
      and percentage of women with DCIS or breast cancer who were treated with BCT
      increased until 2005, then it fell, and the percentage varied between counties.
      The reasons for this need to be identified and followed up with regard to the
      recommendations from the Norwegian Breast Cancer Group.

PMID- 23970272
TI  - Work files as learning tools in knowledge management.
AB  - BACKGROUND: Modern medicine requires doctors to be able to identify, assess and
      use best current research evidence in their own practice. We have developed an
      educational programme in knowledge management integrated in clinical practice
      with the aid of specially designed work files and an online training course. A
      work file is an electronic form that documents the process from clinical
      questions to answers. MATERIAL AND METHOD: A cohort of medical students in their
      10th semester at the University of Oslo completed two work files based on their
      own clinical questions identified during a 10 week clinical placement period in
      hospitals. Submitted work files were assessed and the answers in each field were
      categorised. We present results from one work file from each student. RESULTS: We
      received 91 work files from a total of 107 students. Answers to clinical
      questions were most frequently drawn from recommendations in evidence-based
      textbooks (n = 43), followed by primary studies (n = 30), systematic reviews (n =
      15) and non-disclosed sources (n = 3). The students' critical appraisal of the
      articles revealed a varying degree of understanding of methods, interpretation of
      results and applicability. We nevertheless assessed the conclusion as
      satisfactory for 84 work files. In one-fifth of the work files, the students
      concluded that there was a need to change prevailing practice. INTERPRETATION: At
      the end of their medical studies, the majority of the students are able to
      undertake appropriate literature searches and find answers to clinical questions
      in the best information resources available. A majority of the students require
      more training in critical appraisal of validity and interpretation of results.

PMID- 23970273
TI  - Treatment of congenital syndactyly of the fingers.
AB  - BACKGROUND: Syndactyly or webbed fingers is one of the most common congenital
      malformations of the upper extremities, but it comprises few new cases annually.
      The purpose of treatment is to enhance hand function. METHOD: The article is
      based on current text books and literature searches in PubMed as well as the
      authors' clinical experience within this field. RESULTS: The purpose of surgical
      treatment is to separate the fingers and reconstruct a webspace. It is difficult
      to indicate exact treatment results because of large variations in the extent of
      the deformity. For syndactyly involving only soft tissue (simple syndactyly), a
      good functional result is achieved with a less than 10% risk of complications.
      Syndactyly where also the bones have fused (complex syndactyly) or where there is
      additional bone formation between two digital rays (complicated syndactyly),
      gives a poorer functional outcome and a higher risk of complications. Gradual
      stretching of the tissue using a distraction device enables separation of fingers
      one was previously reluctant to separate. INTERPRETATION: It should be possible
      to expect safe separation with a good and independent function of the fingers
      with surgical treatment. The parents should be informed that the surgical
      treatment is a reconstructive procedure that may require secondary corrections.

PMID- 23970274
TI  - [Delirium in elderly patients].
AB  - BACKGROUND: Delirium, "acute confusional state", is a frequent and serious
      complication of acute illness, particularly in the elderly. The strain on the
      patient, the next of kin and the health service is considerable. The purpose of
      the article is to provide healthcare personnel who deal with delirium with
      updated information about the condition. METHOD: The article is based on a
      literature search in PubMed combined with articles from the author's own archives
      and own clinical experience. RESULTS: Delirium is a serious acute medical
      condition that is often overlooked in the elderly. The prevalence is estimated to
      be between 11% and 42% for elderly patients on medical wards and close to 50% in
      patients with hip fractures. The prevalence is probably also high in nursing
      homes, but this is less well surveyed. Advanced age and dementia are the most
      important risk factors. Traumas, infections, stroke and metabolic disturbances
      are the most common triggering factors. The pathophysiology is poorly surveyed
      and the possibilities for drug treatment are few and are little studied. Delirium
      is associated with increased risk of dementia, loss of function and mortality.
      Short-term use of low-dosage antipsychotics is the first-line choice, but is
      contraindicated for patients with Parkinsonian symptoms. INTERPRETATION:
      Detection and treatment of triggering causes must have high priority in case of
      delirium. Non-drug interventions are most important to prevent and treat the
      condition.

PMID- 23970275
TI  - Subdural empyema.

PMID- 23970276
TI  - A man in his 50s with electrical storm after myocardial infarction.

PMID- 23970277
TI  - The cardiologist's nightmare.

PMID- 23970278
TI  - Pitfalls for the health services.

PMID- 23970279
TI  - From clinical questions to trustworthy answers.

PMID- 23970280
TI  - The Journal of the Norwegian Medical Association should impose stricter
      requirements to literature searches.

PMID- 23970281
TI  - Surgery and task shifting in the rainforest.

PMID- 23970282
TI  - [An embolus, multiple emboli--or?].

PMID- 23970286
TI  - Diet-induced obesity promotes murine gastric cancer growth through a
      nampt/sirt1/c-myc positive feedback loop.
AB  - Obesity increases the risk of gastric cancer and may promote its growth, as was
      recently demonstrated by our novel in vivo mouse model. However, the underlying
      mechanisms of this correlation remain unclear. The purpose of this study was to
      investigate the precise effects of obesity on gastric cancer growth and to
      elucidate the potential molecular mechanisms. Diet-induced obese mice were
      insulin-resistant, glucose-intolerant and had high serum visfatin concentration.
      In the subcutaneous mouse model, tumors were more aggressive in diet-induced
      obese mice compared with lean mice. Tumor weights showed a significant positive
      correlation with mouse body weights, as well as serum insulin and visfatin
      concentrations. Immunohistochemical staining showed that the expression levels of
      iNampt, Sirt1 and c-MYC proteins were upregulated in the subcutaneous tumors from
      obese mice compared to those from lean animals. Furthermore, obesity not only
      prompted significantly murine forestomach carcinoma cell migration,
      proliferation, but also affected cellular apoptosis and cell cycle by endocrine
      mechanisms. These were associated with increased expression of the pro-survival
      nampt/sirt1/c-myc positive feedback loop confirmed by RT-PCR and western
      blotting. These results suggested that diet-induced obesity could promote murine
      gastric cancer growth by upregulating the expression of the nampt, sirt1 and c
      myc genes. 

PMID- 23970287
TI  - hClock gene expression in human colorectal carcinoma.
AB  - In this study, we aimed to investigate changes in the expression of human Clock
      (hClock), a gene at the core of the circadian gene family, in colorectal
      carcinomas (CRCs) and to discuss the possible effects. Previous studies have
      revealed that the disruption of circadian rhythms is one of the endogenous
      factors that contribute to the initiation and development of CRCs. However, the
      underlying molecular changes to the circadian genes associated with CRCs have not
      been explored. Immunofluorescence and quantitative polymerase chain reaction
      (qPCR) analysis of the hCLOCK protein and gene expression were performed in 30
      cases of CRC. The hCLOCK protein was expressed in all specimens obtained from 30
      CRC patients. Higher levels of hCLOCK expression were observed in human CRC
      tissues compared with the paired non-cancerous tissues. hCLOCK expression was
      significantly higher in poorly differentiated, or late-stage, Dukes' grade tumors
      and in 64.3% of tumor cases with lymph node metastasis. The hClock gene was
      expressed in all specimens. A significantly higher expression of hClock was found
      in human CRC cases compared with paired non-cancerous tissues. There was a strong
      positive linear correlation between hClock gene expression and protein expression
      in human CRCs. A strong positive linear correlation was also found between hClock
      gene expression and ARNT, HIF-1alpha and VEGF expression in human CRCs. There was
      no significant correlation between hClock and Bak, Bax, Bid, tumor necrosis
      factor receptor I (TNFR I) and TNFR II. The circadian gene hClock was stably
      expressed in human colorectal mucosa and was important in regulating the
      expression of downstream clock-controlled genes. hCLOCK may interact with HIF
      1alpha/ARNT and activate VEGF to stimulate tumor angiogenesis and metastasis.

PMID- 23970288
TI  - The novel synthetic compound 6-acetyl-9-(3,4,5-trimetho-xybenzyl)-9H-pyrido[2,3
      b]indole induces mitotic arrest and apoptosis in human COLO 205 cells.
AB  - A novel synthetic compound 6-acetyl-9-(3,4,5-trimetho-xybenzyl)-9H-pyrido[2,3
      b]indole (HAC-Y6) demonstrated selective anticancer activity. In the present
      study, COLO 205 cells were treated with HAC-Y6 to investigate the molecular
      mechanisms underlying its effects. HAC-Y6 induced growth inhibition, G2/M arrest
      and apoptosis in COLO 205 cells with an IC50 of 0.52+/-0.035 uM. Annexin V/PI
      double staining demonstrated the presence of apoptotic cells. JC-1 staining
      analysis showed that HAC-Y6 decreased mitochondrial membrane potential in support
      of apoptosis. An immunostaining assay revealed that HAC-Y6 depolymerized
      microtubules. Treatment of COLO 205 cells with HAC-Y6 resulted in increased
      expression of BubR1 and cyclin B1 and decreased expression of aurora A, phospho
      aurora A, aurora B, phospho-aurora B and phospho-H3. HAC-Y6 treatment increased
      protein levels of active caspase-3, caspase-9, Endo G, AIF, Apaf-1, cytochrome c
      and Bax, but treatment with the compound caused reduced levels of procaspase-3,
      procaspase-9, Bcl-xL and Bcl-2. Overall, our results suggest that HAC-Y6 exerts
      anticancer effects by disrupting microtubule assembly and inducing G2/M arrest,
      polyploidy and apoptosis via mitochondrial pathways in COLO 205 cells.

PMID- 23970290
TI  - Promoting public discussion of death through social media.

PMID- 23970289
TI  - Atypical microorganisms in expressed prostatic secretion from patients with
      chronic prostatitis/chronic pelvic pain syndrome: microbiological results from a
      case-control study.
AB  - OBJECTIVES: To investigate the microorganisms in expressed prostatic secretions
      (EPS) of both chronic prostatitis patients and normal young male adults and to
      determine which microorganisms are associated with the degree of intraprostatic
      inflammation. METHODS: Specific polymerase chain reaction (PCR) technology was
      performed to confirm Neisseria gonorrhoeae, Mycobacterium tuberculosis,
      Mycoplasma and Chlamydia trachomatis as well as human papilloma virus (HPV),
      herpes simplex virus type 2 (HSV-2) and cytomegalovirus (CMV). Universal primer
      PCR technology was carried out to detect 16S bacteria rDNA, followed by cloning
      and sequencing of the entire 16S rDNA product. RESULTS: The total number of
      bacteria and/or viruses detected by PCR assays was significantly associated with
      disease severity (p < 0.001). The white blood cell count and lecithin level was
      significantly correlated with the number of detected bacteria and/or viruses (p =
      0.001 and p = 0.046, respectively). 17 bacterial isolates were identified from 14
      EPS samples by 16S rDNA sequencing. CONCLUSIONS: Various microorganisms including
      Ureaplasma urealyticum, C. trachomatis, CMV, HPV and HSV-2 were identified in the
      EPS from patients with type III prostatitis. HPV infection may be associated with
      the degree of intraprostatic inflammation.

PMID- 23970291
TI  - The withdrawal of the Liverpool Care Pathway in England: implications for
      clinical practice and policy.

PMID- 23970292
TI  - What went wrong with the Liverpool Care Pathway and how can we avoid making the
      same mistakes again?

PMID- 23970293
TI  - Living and dying with heart failure in long-term care: experiences of residents
      and their family members.
AB  - The purpose of this study was to explore the experiences of long-term care (LTC)
      residents living and dying with heart failure (HF)and their family members. An
      exploratory descriptive design was used to collect data from seven LTC residents
      and seven family members. The data was analysed using thematic content analysis.
      The main themes that emerged from the data were: limited understanding of the HF
      diagnosis, living with restrictions and other comorbidities, making decisions
      about transitioning to end-of-life care, and learning and negotiating the lines
      of communication. Residents and family members communicated with many health-care
      providers about managing the HF symptoms but most often worked through the nurse
      when problems arose or decisions about care needed to be made. The findings from
      this study contribute to our understanding of residents' and family members'
      experiences in managing residents' HF in LTC. 

PMID- 23970294
TI  - Essential knowledge for family caregivers: a qualitative study.
AB  - BACKGROUND: Family caregivers are the backbone of the social care delivery
      system. With cancer and other life-limiting diseases on the rise, the need for
      well-informed informal/family caregivers has never been greater. AIM: To uncover
      the information that palliative care teams routinely provide to family
      caregivers. DESIGN: The methodology used was the nominal group technique, a type
      of focus group. PARTICIPANTS: A total of 17 community palliative care health
      professionals participated in one of three focus groups. RESULTS: Three themes
      emerged as dominant priorities for the education of family caregivers: caring for
      oneself physically, emotionally, and spiritually; learning practical skills; and
      knowing what to expect and plan for as the family member's health declines.
      CONCLUSIONS: The participants encourage caregivers to meet their own needs as
      well as care for family members. They help to empower family caregivers by
      encouraging them to take time for themselves, providing practical information for
      individual situations, and educating them on the signs and symptoms of
      approaching death. Successful terminal home care is possible through family
      caregiver support and empowerment.

PMID- 23970295
TI  - Exploring the advance care planning needs of moderately to severely ill people
      with COPD.
AB  - BACKGROUND: There is no clear consensus on how to approach advance care planning
      (ACP) with people with chronic obstructive pulmonary disease (COPD). AIM: This
      study aimed to explore the perceived ACP needs of people with COPD and to
      investigate the usefulness of a DVD in meeting these needs. METHODS: A
      qualitative descriptive design was used. Twelve people with moderate to severe
      COPD were interviewed in an outpatient clinic. RESULTS: From the themes elicited,
      a mental model was created to demonstrate how the participants engaged in a
      process of mental work to accept their own mortality and subsequently engage in
      ACP. CONCLUSIONS: Health professionals should not rely solely on illness severity
      to initiate ACP. Rather, patients from different illness categories should be
      approached, but with sensitivity to their emotional cues. Participants who were
      receptive to end-of-life issues enjoyed the DVD. The DVD is a good medium to
      facilitate discussion, but would be more effective if patients were screened for
      readiness prior to viewing.

PMID- 23970296
TI  - Nurses' perspectives on the discharge of cancer patients with palliative care
      needs from a gastroenterology ward.
AB  - BACKGROUND: People with cancer usually like to spend as much time as possible at
      home rather than in the hospital. Nurses have a pivotal role when patients are
      discharged to a unit in hospital or from hospital to the community health-care
      system. AIM: To explore how frontline surgical nurses assess patients with
      gastrointestinal cancer receiving palliative care and the implications of their
      assessment and competency for the patients' discharge destinations. METHODS: A
      descriptive exploratory approach was used involving focus group interviews with a
      purposive sample of ten nurses from an inpatient gastroenterology surgical ward
      at a university hospital in Norway. Transcriptions of the interviews were
      analysed using Kvale and Brinkman's thematic approach. RESULTS: Two overall
      themes emerged that had implications for the nurses' recommendations for optimal
      patient follow-up care after discharge: 'the complexity of and fluctuations in
      the patients' health status' and 'considering the competency of the nurses at the
      discharge destinations'. CONCLUSIONS: This study illustrates surgical nurses'
      perspectives on the discharge destinations of cancer patients receiving
      palliative care. The findings have implications for initiatives aimed at
      providing more home-based palliative care.

PMID- 23970297
TI  - Nurses' attitudes toward palliative care in south-east Iran.
AB  - BACKGROUND: Nurses are the element of the palliative care team who spend the most
      time with patients. Nurses' attitudes toward palliative care affect their
      behaviour toward their patients. AIM: This study sought to examine oncology and
      intensive care unit (ICU) nurses' attitudes toward palliative care in south-east
      Iran. METHODS: A self-administered questionnaire was used to assess the
      palliative care attitudes of 140 oncology and ICU nurses from three hospitals
      supervised by Kerman University of Medical Science. RESULTS: Participants had
      moderately negative to neutral attitudes toward palliative care (2.99 +/- 0.29
      out of 5). Among all categories, the highest mean score came from the category of
      'patient's preferences' (mean=3.66) and the lowest from the category of
      'withholding and withdrawing treatment' (mean=2.42). A significant correlation
      was found between nurses' attitudes toward palliative care and some demographic
      characteristics, including marital status, type of ward, palliative care
      education, personal study about palliative care, level of education, and
      experience of caring for a dying family member. CONCLUSIONS: This study suggests
      that educational designers should include specific courses about death and
      palliative care in undergraduate and postgraduate nursing curricula. Educational
      programmes need to build on the specific experiences of death and dying among
      nurses and auxiliary nurses.

PMID- 23970300
TI  - B7-H1 protein vaccine induces protective and therapeutic antitumor responses in
      SP2/0 myeloma-bearing mice.
AB  - B7-H1 is a co-inhibitory molecule belonging to the B7 family. The B7-H1 protein
      is only expressed on macrophage lineage of cells in normal tissues, but is
      overexpressed in most types of tumor. The aberrant expression of cell surface B7
      H1 on cancer cells is generally associated with high-risk prognostic factors. The
      tumor-associated B7-H1 increases apoptosis of antigen-specific T cells through
      interaction with its receptor PD-1 on CD8+ T cells and contributes to tumor
      immune evasion. These features suggest that B7-H1 may be a therapeutic target for
      the B7-H1-expressing tumors. We developed a therapeutic vaccine by coupling a
      tetanus toxoid T-helper cell epitope with the N-terminal of B7-H1 IgV-like
      domain. This vaccine was able to induce high titers of antibodies against B7-H1
      in mice which were able to bind to native cell surface B7-H1. We chose the B7-H1
      expressing SP2/0 myeloma and its syngeneic host (the BALB/c mouse) as the model
      to study the antitumor activity of the rhB7-H1M vaccine. Vaccination with this
      modified B7-H1 protein resulted in almost complete protection from SP2/0 tumor
      challenge and efficiently eliminated pre-established tumors in mice. In addition,
      B7-H1 vaccination was able to decrease the percentage of CD4+ Foxp3+ regulatory T
      cells in tumor-bearing mice and which might improve antitumor immunity. These
      data demonstrate the potential of B7-H1-based vaccine as a therapeutic agent for
      the treatment of cancer overexpressing B7-H1. 

PMID- 23970301
TI  - Autophagy is used as a survival program in unfertilized sea urchin eggs that are
      destined to die by apoptosis after inactivation of MAPK1/3 (ERK2/1).
AB  - A high MAPK1/3 (also known as ERK2/1, respectively) activity, preventing
      spontaneous activation, is essential to maintain cell cycle arrest of mature
      oocytes of mammals, frogs or invertebrates such as starfish. Mature oocytes would
      undergo a "suicide"-like cell death if not fertilized. We previously have
      reported that downregulation of MAPK1/3 in unfertilized sea urchin eggs induces a
      calcium-dependent entry into mitosis. We show here that this event is followed by
      a series of pseudo-mitotic cell cycles associated with transient Cai increases,
      preceding CASP3/caspase-3 activation and apoptosis. However, cell death was
      delayed after inhibition of the Cai transients or of cyclin-dependent kinases
      (CDK), with roscovitine. In these conditions, eggs enter an autophagy program as
      suggested by detection of processed LC3B by western blot, immunofluorescence and
      immunogold staining, visualization of autophagy vesicles by electron microscopy,
      and an increase in acidic vesicular organelles (AVOs). We found that bafilomycin
      A 1 or an association of leupeptin and pepstatin, which are widely used to study
      autophagy, may act upon calcium signaling or cell cycle events, respectively, and
      not only on autophagy events. Finally, inhibition of PtdIns 3-kinase with
      wortmannin or LY294002 powerfully stimulated cell death of unfertilized eggs,
      which suggests that this activity does not negatively regulate autophagy as is
      often reported, but rather stimulates survival in unfertilized eggs. We suggest
      that apoptosis of unfertilized eggs is the consequence of an aberrant short
      attempt of development that occurs if MAPK1/3 is inactivated, but these eggs can
      use autophagy as a survival program when the cell cycle is blocked. 

PMID- 23970302
TI  - Phenytoin versus valproate monotherapy for partial onset seizures and generalised
      onset tonic-clonic seizures.
AB  - BACKGROUND: This is an updated version of the previously published Cochrane
      review (Issue 4, 2009)Worldwide, phenytoin and valproate are commonly used
      antiepileptic drugs. It is generally believed that phenytoin is more effective
      for partial onset seizures, and that valproate is more effective for generalised
      onset tonic-clonic seizures with or without other generalised seizure types.
      OBJECTIVES: To review the best evidence comparing phenytoin and valproate when
      used as monotherapy in individuals with partial onset seizures or generalised
      onset tonic-clonic seizures with or without other generalised seizure types.
      SEARCH METHODS: We searched the Cochrane Epilepsy Group's Specialised Register
      (19 February 2013), the Cochrane Central Register of Controlled Trials (CENTRAL,
      Issue 1, The Cochrane Library, January 2013), MEDLINE (1946 to 18 February 2013),
      SCOPUS (19 February 2013), ClinicalTrials.gov (19 February 2013), and WHO
      International Clinical Trials Registry Platform ICTRP (19 February 2013). We
      handsearched relevant journals, contacted pharmaceutical companies, original
      trial investigators and experts in the field. SELECTION CRITERIA: Randomised
      controlled trials in children or adults with partial onset seizures or
      generalised onset tonic-clonic seizures with a comparison of valproate
      monotherapy versus phenytoin monotherapy. DATA COLLECTION AND ANALYSIS: This was
      an individual patient data review. Outcomes were time to (a) treatment withdrawal
      (b) 12-month remission (c) six-month remission and (d) first seizure post
      randomisation. Cox proportional hazards regression models were used to obtain
      study-specific estimates of hazard ratios (HRs) with 95% confidence intervals
      (CIs) with the generic inverse variance method used to obtain the overall pooled
      HR and 95% CI. MAIN RESULTS: Individual patient data were available for 669
      individuals out of 1119 eligible individuals from five out of 11 trials, 60% of
      the potential data. Results apply to generalised tonic-clonic seizures, but not
      absence or myoclonus seizure types. For remission outcomes, HR > 1 indicates an
      advantage for phenytoin and for first seizure and withdrawal outcomes HR > 1
      indicates an advantage for valproateThe main overall results (pooled HR adjusted
      for seizure type, 95% CI) were time to (a) withdrawal of allocated treatment 1.09
      (0.76 to 1.55); (b) 12-month remission 0.98 (0.78 to 1.23); (c) six-month
      remission 0.95 (0.78 to 1.15) and (d) first seizure 0.93 (0.75 to 1.14). The
      results suggest no overall difference between the drugs for these outcomes. No
      statistical interaction between treatment and seizure type (partial versus
      generalised) was found, but misclassification of seizure type may have confounded
      the results of this review. AUTHORS' CONCLUSIONS: We have not found evidence that
      a significant difference exists between phenytoin and valproate for the outcomes
      examined in this review. However misclassification of seizure type may have
      confounded the results of this review. Results do not apply to absence or
      myoclonus seizure types. No outright evidence was found to support or refute
      current treatment policies.

PMID- 23970303
TI  - Micro flow reactor chips with integrated luminescent chemosensors for spatially
      resolved on-line chemical reaction monitoring.
AB  - Real-time chemical reaction monitoring in microfluidic environments is
      demonstrated using luminescent chemical sensors integrated in PDMS/glass-based
      microscale reactors. A fabrication procedure is presented that allows for
      straightforward integration of thin polymer layers with optical sensing
      functionality in microchannels of glass-PDMS chips of only 150 MUm width and of
      10 to 35 MUm height. Sensor layers consisting of polystyrene and an oxygen
      sensitive platinum porphyrin probe with film thicknesses of about 0.5 to 4 MUm
      were generated by combining spin coating and abrasion techniques. Optimal coating
      procedures were developed and evaluated. The chip-integrated sensor layers were
      calibrated and investigated with respect to stability, reproducibility and
      response times. These microchips allowed observation of dissolved oxygen
      concentration in the range of 0 to over 40 mg L(-1) with a detection limit of 368
      MUg L(-1). The sensor layers were then used for observation of a model reaction,
      the oxidation of sulphite to sulphate in a microfluidic chemical reactor and
      could observe sulphite concentrations of less than 200 MUM. Real-time on-line
      monitoring of this chemical reaction was realized at a fluorescence microscope
      setup with 405 nm LED excitation and CCD camera detection. 

PMID- 23970304
TI  - Feasibility of laparoscopic intersphincteric resection for patients with cT1-T2
      low rectal cancer.
AB  - AIMS: The purpose of this study was to assess the feasibility of laparoscopic
      intersphincteric resection (LAP-ISR) for rectal cancer in terms of morbidity,
      oncological outcomes, and functional results. METHODS: Thirty-seven patients with
      primary low rectal cancer cT1-T2 underwent LAP-ISR. Surgical outcomes,
      pathological results, postoperative complications, oncological outcomes, and
      functional results were analyzed retrospectively. RESULTS: Three patients (8.1%)
      had carcinoma in situ, 22 (59.5%) had pT1 tumor, and 11 (29.7%) had pT2 tumor.
      Eleven patients (29.7%) were diagnosed as being node positive, while 26 (70.3%)
      had node-negative disease. The median operative time was 315 min (range: 195
      502). The median blood loss was 37 ml (range: 0-745). One case was converted to
      open surgery. Pathological complete resection was achieved in all cases. There
      was no surgical mortality. Postoperative complications of grade III-IV on the
      Clavien-Dindo classification were observed in 16.2% of the patients. The median
      follow-up period was 2.8 years (range: 187-2,241 days), and 3-year disease-free
      survival was 93.1%. No patient developed local recurrence. The functional result
      was objectively good. CONCLUSION: LAP-ISR can be recommended as a feasible,
      ultimate sphincter-preserving procedure with acceptable functional and
      intermediate-term oncological outcomes in patients with cT1-T2 very low rectal
      cancer.

PMID- 23970305
TI  - Effects of parenteral nutrition formulas on plasma lipid profile in children with
      bone marrow transplantation.
AB  - BACKGROUND/AIMS: Children undergoing bone marrow transplantation (BMT) often
      require parenteral nutrition (PN). This is a comparative study of plasma lipid
      profiles in BMT children after fish oil or soybean PN. METHODS: A total of 14
      children with BMT requiring PN for at least 10 days were recruited during 24
      months. They were randomized to receive a lipid emulsion enriched with omega3
      polyunsaturated fatty acid, or soybean oil. Clinical monitoring was performed.
      Blood samples were collected before and after administration of PN to analyze the
      lipid profile. RESULTS: There were no complications associated with PN. The
      increase in TG levels was more pronounced after administration of an enriched
      omega3 emulsion and the decrease in cHDL and apo A was greater after
      administration of soybean. The omega3 group showed an increase in
      eicosapentaenoic and a decrease in arachidonic acids compared to the soybean
      group. Both groups showed similar levels of linolenic acid. CONCLUSION: PN with
      soybean or omega3 emulsions for 10 days is safe in children. However, research in
      children are necessary in order to examine the impact of the duration of PN and
      the type of lipid formula used, and determine their health benefits in relation
      to the fatty acid profile.

PMID- 23970306
TI  - Bacterial lipopolysaccharide inhibits influenza virus infection of human
      macrophages and the consequent induction of CD8+ T cell immunity.
AB  - It is well established that infection with influenza A virus (IAV) facilitates
      secondary bacterial disease. However, there is a growing body of evidence that
      the microbial context in which IAV infection occurs can affect both innate and
      adaptive responses to the virus. To date, these studies have been restricted to
      murine models of disease and the relevance of these findings in primary human
      cells remains to be elucidated. Here, we show that pre-stimulation of primary
      human monocyte-derived macrophages (MDMs) with the bacterial ligand
      lipopolysaccharide (LPS) reduces the ability of IAV to infect these cells. The
      inhibition of IAV infection was associated with a reduced transcription of viral
      RNA and the ability of LPS to induce an anti-viral/type I interferon response in
      human MDMs. We demonstrated that this reduced rate of viral infection is
      associated with a reduced ability to present a model antigen to autologous CD8+ T
      cells. Taken together, these data provide the first evidence that exposure to
      bacterial ligands like LPS can play an important role in modulating the immune
      response of primary human immune cells towards IAV infection, which may then have
      important consequences for the development of the host's adaptive immune
      response. 

PMID- 23970307
TI  - Copper-catalyzed free-radical C-H arylation of pyrroles.
AB  - A room temperature copper-catalyzed radical arylation of pyrroles with anilines,
      through in situ generated aryl diazonium salts, has been developed under neutral
      conditions. Experimental and theoretical studies explain the crucial role of
      CaCO3 and the high regioselectivity observed. 

PMID- 23970308
TI  - The Pampulha reservoir remains a potential urban focus of schistosomiasis mansoni
      in Brazil: changes in the occurrence patterns of Biomphalaria species and a new
      record of the parasite.
AB  - INTRODUCTION: The Pampulha reservoir has long been a focus of schistosomiasis
      transmission in Belo Horizonte, State of Minas Gerais, Brazil. The last
      malacological study conducted in this urban reservoir was more than two decades
      ago, and thus, an update on the distribution of the species of Biomphalaria as
      well as new data on the presence of Schistosoma mansoni in this water body are
      required. METHODS: The current distribution of Biomphalaria spp. in the Pampulha
      reservoir and their infection with S. mansoni was evaluated during 55
      malacological surveys conducted between 2009 and 2012. RESULTS: Biomphalaria
      straminea displayed a high population density and distribution, and 13.7%
      (2,233/16,235) of the specimens collected were infected with larval trematodes
      other than Schistosoma mansoni. Biomphalaria tenagophila and Biomphalaria
      glabrata, species currently presenting a restricted distribution and small
      populations, displayed trematode infection rates of 15.2% (98/644) and 13%
      (83/640), respectively. Thirteen (2%) specimens of B. glabrata were found to be
      infected with S. mansoni. In addition, a historical review based on previous and
      new data on the occurrence patterns of Biomphalaria species in this reservoir is
      presented. CONCLUSIONS: The results indicate that the Pampulha reservoir remains
      a potential focus of urban schistosomiasis in Brazil, and significant changes in
      the occurrence patterns of Biomphalaria species were verified.

PMID- 23970309
TI  - Bloodstream infection in patients with end-stage renal disease in a teaching
      hospital in central-western Brazil.
AB  - INTRODUCTION: Vascular access in patients undergoing hemodialysis is considered a
      critical determinant of bloodstream infection (BSI) and is associated with high
      morbidity and mortality. The purpose of this study was to investigate the
      occurrence of BSI in patients with end-stage renal disease using central venous
      catheters for hemodialysis. METHODS: A cohort study was conducted in a public
      teaching hospital in central-western Brazil from April 2010 to December 2011. For
      every patient, we noted the presence of hyperemia/exudation upon catheter
      insertion, as well as fever, shivering, and chills during hemodialysis. RESULTS:
      Fifty-nine patients were evaluated. Thirty-fi ve (59.3%) patients started
      dialysis due to urgency, 37 (62.7%) had BSI, and 12 (20%) died. Hyperemia at the
      catheter insertion site (64.9%) was a significant clinical manifestation in
      patients with BSI. Statistical analysis revealed 1.7 times more cases of BSI in
      patients with hypoalbuminemia compared with patients with normal albumin levels.
      The principal infective agents identified in blood cultures and catheter-tip
      cultures were Staphylococcus species (24 cases), non-fermentative Gram-negative
      bacilli (7 cases of Stenotrophomonas maltophilia and 5 cases of Chryseobacterium
      indologenes), and Candida species (6). Among the Staphylococci identified, 77.7%
      were methicillin-resistant, coagulase-negative Staphylococci. Of the bacteria
      isolated, the most resistant were Chryseobacterium indologenes and Acinetobacter
      baumannii. CONCLUSIONS: Blood culture was demonstrated to be an important
      diagnostic test and identified over 50% of positive BSI cases. The high frequency
      of BSI and the isolation of multiresistant bacteria were disturbing findings.
      Staphylococcus aureus was the most frequently isolated microorganism, although
      Gram-negative bacteria predominated overall. These results highlight the
      importance of infection prevention and control measures in dialysis units.

PMID- 23970310
TI  - Larvicidal effects of endophytic and basidiomycete fungus extracts on Aedes and
      Anopheles larvae (Diptera, Culicidae).
AB  - INTRODUCTION: In vitro bioassays were performed to access the larvicidal activity
      of crude extracts from the endophytic fungus Pestalotiopsis virgulata
      (Melanconiales, Amphisphaeriaceae) and the saprophytic fungus Pycnoporus
      sanguineus (Basidiomycetes, Polyporaceae) against the mosquitoes Aedes aegypti
      and Anopheles nuneztovari. METHODS: The extracts were tested at concentrations of
      100, 200, 300, 400 and 500ppm. Ethyl acetate mycelia (EAM) extracts and liquid
      culture media (LCM) from Pe. virgulata and Py. sanguineus were tested against
      third instar larvae of Ae. aegypti and An. nuneztovari. RESULTS: The larvicidal
      activity of the EAM extracts from Pe. virgulata against Ae. aegypti had an
      LC50=101.8ppm, and the extract from the basidiomycete fungus Py. sanguineus had
      an LC50=156.8ppm against the Ae. aegypti larvae. The Pe. virgulata extract had an
      LC50=16.3ppm against the An. nuneztovari larvae, and the Py. sanguineus extract
      had an LC50=87.2ppm against these larvae. CONCLUSIONS: These results highlight
      the larvicidal effect of EAM extracts from the endophyte Pe. virgulata against
      the two larval mosquitoes tested. Thus, Pe. virgulata and Py. sanguineus have the
      potential for the production of bioactive substances against larvae of these two
      tropical disease vectors, with An. nuneztovari being more susceptible to these
      extracts.

PMID- 23970311
TI  - Contributions of culture and antimicrobial susceptibility tests to the
      retreatment of patients with pulmonary tuberculosis.
AB  - INTRODUCTION: This study evaluated the efficacy of retreatment of pulmonary
      tuberculosis (TB) with regard to treatment outcomes and antimicrobial
      susceptibility testing (ST) profiles. METHODS: This retrospective cohort study
      analyzed 144 patients treated at a referral hospital in Brazil. All of them had
      undergone prior treatment, were smear-positive for TB and received a standardized
      retreatment regimen. Fisher's 2-tailed exact test and the chi2 test were used;
      RRs and 95% CIs were calculated using univariate and multivariate binary logistic
      regression. RESULTS: The patients were cured in 84 (58.3%) cases. Failure was
      associated with relapsed treatment and abandonment (n=34). Culture tests were
      obtained for 103 (71.5%) cases; 70 (48.6%) had positive results. ST results were
      available for 67 (46.5%) cases; the prevalence of acquired resistance was 53.7%.
      There were no significant differences between those who achieved or not
      therapeutic success (p=0.988), despite being sensitive or resistant to 1 or more
      drugs. Rifampicin resistance was independently associated with therapeutic
      failure (OR: 4.4, 95% CI:1.12-17.37, p=0.034). For those cases in which cultures
      were unavailable, a 2nd model without this information was built. In this, return
      after abandonment was significantly associated with retreatment failure (OR:
      3.59, 95% CI:1.17-11.06, p=0.026). CONCLUSIONS: In this cohort, the general
      resistance profile appeared to have no influence on treatment outcome, except in
      cases of rifampicin resistance. The form of reentry was another independent
      predictor of failure. The use of bacterial culture identification and ST in TB
      management must be re-evaluated. The recommendations for different susceptibility
      profiles must also be improved.

PMID- 23970312
TI  - Pediatric epidemiological aspects of scorpionism and report on fatal cases from
      Tityus stigmurus stings (Scorpiones: Buthidae) in State of Pernambuco, Brazil.
AB  - INTRODUCTION: Envenomation by scorpion stings is a major public health problem in
      numerous tropical countries because of its frequent incidence and potential
      severity. Approximately 1,900 species of scorpions are known in the world, and at
      least 130 of these have been described in Brazil. METHODS: This work reports on 3
      child deaths caused by Tityus stigmurus stings and characterizes epidemiological
      and clinical surveys on pediatric cases of scorpionism recorded in the Centro de
      Assistencia Toxicologica de Pernambuco (Ceatox-PE). RESULTS: Scorpion stings
      accounted for more than 60% of all cases recorded for venomous animals. The
      children were from 37 cities of the State of Pernambuco and accounted for 28.8%
      of the victims treated for scorpion stings, with the highest incidence in the
      metropolitan area of Recife. Stings occurred throughout the year and slightly
      increased during the rainy season. Independent of the elapsed time for a
      prognosis, most cases showed mild symptoms. Three moderate cases that resulted in
      death featured cardiogenic shock and/or pulmonary edema or severe neurological
      symptoms. For the fi rst time, death attributed to T. stigmurus was confirmed by
      the presence of the scorpion. CONCLUSIONS: These results suggest that scorpionism
      in Pernambuco is a public health problem that needs to be monitored carefully
      throughout the year by the government.

PMID- 23970315
TI  - Maximizing information content of single-molecule FRET experiments: multi-color
      FRET and FRET combined with force or torque.
AB  - Since its first demonstration about twenty years ago, single-molecule
      fluorescence resonance energy transfer (FRET) has undergone remarkable technical
      advances. In this tutorial review, we will discuss two technical advances that
      increase the information content of the single-molecule FRET measurements: single
      molecule multi-color FRET and single-molecule FRET combined with force or torque.
      Our expectations for future developments will be briefly discussed at the end. 

PMID- 23970313
TI  - Does HIV infection promote early kidney injury in women?
AB  - BACKGROUND: In HIV-infected women, urine concentrations of novel
      tubulointerstitial injury markers, interleukin-18 (IL-18) and kidney injury
      marker-1 (KIM-1), are associated with kidney function decline and all-cause
      mortality. We hypothesized that HIV-infected individuals with preserved kidney
      filtration function would have more extensive kidney injury, as determined by
      urine injury markers, compared to the uninfected controls, and that risk factors
      for tubulointerstitial injury would differ from risk factors for albuminuria.
      METHODS: In this cross-sectional study, we compared urine concentrations of IL
      18, KIM-1 and albumin-to-creatinine ratio (ACR) in 908 HIV-infected and 289 HIV
      uninfected women enrolled in the Women's Interagency HIV Study, utilizing stored
      urine specimens from visits between 1999 and 2000. RESULTS: After multivariate
      adjusted linear regression analysis, mean urine concentrations were higher in HIV
      infected individuals by 38% for IL-18 (P<0.0001), 12% for KIM-1 (P=0.081) and 47%
      for ACR (P<0.0001). Higher HIV RNA level (15% per 10-fold increase; P<0.0001),
      lower CD4(+) lymphocyte count (8% per doubling; P=0.0025), HCV infection (30%;
      P=0.00018) and lower high-density lipoprotein (5% per 10 mg/dl; P=0.0024) were
      each associated with higher IL-18 concentrations. In contrast, hypertension (81%;
      P<0.0001) and diabetes (47%; P=0.018) were among the strongest predictors of
      higher ACR, though HIV RNA level (15% per 10-fold increase; P=0.0004) was also
      associated with higher ACR. CONCLUSIONS: HIV-infected women had more extensive
      tubulointerstitial and glomerular injury than uninfected women, but the
      associated factors differed among the urine biomarkers. Combinations of urinary
      biomarkers should be investigated to further characterize early kidney injury in
      HIV-infected women.

PMID- 23970314
TI  - Repeated use of immersive virtual reality therapy to control pain during wound
      dressing changes in pediatric and adult burn patients.
AB  - The current study explored whether immersive virtual reality (VR) continues to
      reduce pain (via distraction) during more than one wound care session per
      patient. Thirty-six patients aged 8 to 57 years (mean age, 27.7 years), with an
      average of 8.4% TBSA burned (range, 0.25-25.5 TBSA) received bandage changes, and
      wound cleaning. Each patient received one baseline wound cleaning/debridement
      session with no-VR (control condition) followed by one or more (up to seven)
      subsequent wound care sessions during VR. After each wound care session (one
      session per day), worst pain intensity was measured using a visual analog
      thermometer, the dependent variable. Using a within-subjects design, worst pain
      intensity during wound care with no-VR (baseline, day 0) was compared with pain
      during wound care while using immersive VR (up to 7 days of wound care during
      VR). Compared with pain during no-VR baseline (day 0), pain ratings during wound
      debridement were statistically lower when patients were in VR on days 1, 2, and
      3, and although not significant beyond day 3, the pattern of results from days 4,
      5, and 6 are consistent with the notion that VR continues to reduce pain when
      used repeatedly. Results from the present study suggest that VR continues to be
      effective when used for three (or possibly more) treatments during severe burn
      wound debridement. 

PMID- 23970316
TI  - Botulinum toxin-A injections for idiopathic overactive bladder: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To review the current evidence on the efficacy and safety of botulinum
      toxin-A in the management of idiopathic overactive bladder (OAB). METHODS: A
      systematic search of PubMed, Embase and the Cochrane Central Search Library was
      performed. All randomized controlled trials comparing botulinum toxin-A with
      placebo, different doses and injection techniques, in patients with idiopathic
      OAB was included. The analyzed outcomes were quantification of symptoms,
      urodynamic outcomes, quality of life and adverse events. RESULT: A total of 1,020
      participants from 12 randomized controlled trials were included. Botulinum toxin
      A was associated with less urinary frequency, less incontinence episodes,
      improvement in quality of life, higher post-void residual-related catheterization
      and higher urinary tract infection. Doses of 100-300 U were not consistently
      differentiated from each other in voiding diary, quality of life and urge urinary
      incontinence. No statistically significant difference was seen between bladder
      body and bladder base, bladder body and bladder body plus trigone in urinary
      retention and urinary tract infection. CONCLUSION: Botulinum toxin-A is
      associated with significant improvement in OAB symptoms in patients with
      idiopathic OAB. However, there is a higher incidence of postoperative urinary
      retention and urinary infection compared to placebo. Low-dose botulinum toxin-A
      seems to be the optimum dose that appropriately balances the benefits with
      adverse events. Trigone inclusion seems as safe and effective as trigone-sparing
      injection.

PMID- 23970317
TI  - High levels of EphA3 expression are associated with high invasive capacity and
      poor overall survival in hepatocellular carcinoma.
AB  - Although EphA3 expression has been associated with progression or prognosis in
      several types of tumors, the role of EphA3 in hepatocellular carcinoma (HCC)
      remains unknown. This study sought to investigate the clinicopathological and
      prognostic relevance of EphA3 expression in HCC as well as the underlying
      mechanisms responsible. EphA3 protein was mainly localized within the cytoplasm
      and at the cell membrane. High EphA3 expression was correlated with tumor size,
      tumor grade, metastasis, venous invasion and AJCC TNM stage (P<0.05), and
      patients with high levels of EphA3 expression were at a significantly increased
      risk for shortened survival time (P<0.05). In vitro, the downregulation of EphA3
      expression decreased the invasive capacity of HCC cells via the regulation of
      VEGF. EphA3 may represent a novel candidate marker for patient prognosis as well
      a molecular target for HCC therapy. 

PMID- 23970318
TI  - Molecular aspects of eye evolution and development: from the origin of retinal
      cells to the future of regenerative medicine.
AB  - A central issue of evolutionary developmental biology is how the eye is diverged
      morphologically and functionally. However, the unifying mechanisms or schemes
      that govern eye diversification remain unsolved. In this review, I first
      introduce the concept of evolutionary developmental biology of the eye with a
      focus on photoreception, the fundamental property of retinal cells. Second, I
      summarize the early development of vertebrate eyes and the role of a homeobox
      gene, Lhx1, in subdivision of the retina into 2 domains, the neural retina and
      retinal pigmented epithelium of the optic primordium. The 2 retinal domains are
      essential components of the eye as they are found in such prototypic eyes as the
      extant planarian eye. Finally, I propose the presence of novel retinal cell
      subtypes with photosensory functions based on our recent work on atypical
      photopigments (opsins) in vertebrates. Since human diseases are attributable to
      the aberration of various types of cells due to alterations in gene expression,
      understanding the precise mechanisms of cellular diversification and unraveling
      the molecular profiles of cellular subtypes are essential to future regenerative
      medicine. 

PMID- 23970319
TI  - Factors influencing breast density in Japanese women aged 40-49 in breast cancer
      screening mammography.
AB  - A relatively large number of women in their 40s with high-density breasts, in
      which it can be difficult to detect lesions, are encountered in mammography
      cancer screenings in Japan. Here, we retrospectively investigated factors related
      to breast density. Two hundred women (40-49 years old) were examined at the
      screening center in our hospital. Multivariate analysis showed that factors such
      as small abdominal circumference, high HDL cholesterol, and no history of
      childbirth were related to high breast density in women in their 40s undergoing
      mammography. Other non-mammographic screening methods should be considered in
      women with abdominal circumferences < 76cm, HDL-C >= 53mg/dl, and no history of
      childbirth, as there is a strong possibility of these women having high-density
      breasts that can make lesion detection difficult.

PMID- 23970320
TI  - Thrombocytopenia at birth is a predictor of cholestasis in infants with small for
      gestational age.
AB  - Cholestasis and thrombocytopenia are complications that affect infants born small
      for gestational age (SGA). In SGA infants, other vital organs develop at the
      expense of the liver, and the thrombopoietin produced by the liver is low, often
      resulting in cholestasis. We hypothesized that thrombocytopenia at birth can be
      used to predict cholestasis in very-low-birth-weight infants (VLBWIs) with SGA.
      This retrospective cohort study enrolled VLBWIs with SGA admitted to a tertiary
      neonatal intensive care unit. A platelet cutoff value predictive of cholestasis
      was determined using receiver operating characteristic analysis. Multivariate
      logistic regression analysis was performed to evaluate the platelet cutoff value,
      and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated. Regarding the onset of cholestasis, survival analysis was performed
      by calculating the adjusted hazard ratios (HRs) and 95% CIs. A total of 87
      infants were evaluated, and the platelet cutoff value was determined as 88*10(3)
      cells/MUl. The adjusted OR for this platelet cutoff value was 10.52 (95% CI 2.26
      55.93, p = 0.003), and the adjusted HR was 7.76 (95% CI 2.51-23.50, p = 0.0006).
      Thrombocytopenia is a useful predictor for cholestasis in VLBWIs with SGA.

PMID- 23970321
TI  - A comprehensive analysis of 174 febrile patients admitted to Okayama University
      Hospital.
AB  - Primary care physicians often encounter patients with fever of unknown origin and
      without apparent causes. Recent advances in laboratory medicine have facilitated
      diagnostic procedures;however, it is still difficult to determine the critical
      febrile factor at an early stage. We reviewed the medical records of 174 patients
      who were admitted due to a chief complaint of fever (>37.5C) to our hospital
      during the period from 2004 to 2010. The patients were categorized into patients
      with infection, inflammation, neoplasm and drug-induced fever. Based on the
      analysis done by category, it was revealed that the patient's age, body
      temperature and duration of fever were closely related to the final diagnosis.
      Serum CRP levels were significantly low in the nonbacterial infection group,
      while serum levels of sIL-2R were high in neoplasm and drug-induced cases. CRP
      level on admission was weakly but significantly correlated with body temperature,
      while duration of fever was inversely related to body temperature. The
      effectiveness of PET-CT and tissue biopsy for diagnosis was considerably high,
      particularly in the categories of neoplasm and nonspecific inflammation,
      respectively, though the effectiveness of bacterial culture was low. Thus, a
      careful review of physical and laboratory information including body temperature,
      CRP level, duration of fever, gender difference and history of medication is
      indispensable for diagnosis. Stepwise categorization and disease classification
      by comprehensive and systemic checkup are very helpful for determining the causes
      of fever.

PMID- 23970322
TI  - The diagnosis of hypovascular hepatic lesions showing hypo-intensity in the
      hepatobiliary phase of Gd-EOB- DTPA-enhanced MR imaging in high-risk patients for
      hepatocellular carcinoma.
AB  - The aim of this study was to evaluate the histologic diagnosis of hypovascular
      hepatic lesions showing hypointensity on hepatobiliary phase images of gadolinium
      ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI (EOB
      MRI). In 38 patients with hepatocellular carcinoma (HCC) after curative
      treatments and 18 patients with liver cirrhosis, 105 hypovascular nodules that
      were hypointense at the hepatobiliary phase of EOB-MRI were biopsied and the
      clinical usefulness of these EOB-MRI findings for the diagnosis of HCC was
      examined. Of the 105 nodules (median diameter = 12mm), 78 (74.3%), 11 (10.5%),
      and 16 (15.2%) were diagnosed as HCC, dysplastic, and non-neoplastic,
      respectively. The positive predictive value (PPV) of hypointensity at the
      hepatobiliary phase of EOB-MRI for the diagnosis of HCC increased to 77-90% when
      combined with the following factors: washout appearance on the delayed phase of
      triple-phase CT, hyperintensity in diffusion-weighted image of MRI, or the
      appearance of a hypoechoic part in ultrasonography. PPV increased to 100% when
      all 3 factors were positive. A relatively large proportion of hypovascular
      lesions that showed hypo-intensity in the hepatobiliary phase were confirmed to
      be HCC, and the accuracy of HCC increased when combined with other imaging
      findings.

PMID- 23970323
TI  - Comparison of 7 alpha(1)-adrenoceptor antagonists in patients with lower urinary
      tract symptoms associated with benign prostatic hyperplasia:a short-term
      crossover study.
AB  - A crossover study was conducted to identify the best alpha1-adrenoceptor
      (alpha1AR) antagonist for individual patients with lower urinary tract symptoms
      (LUTS) associated with benign prostatic hyperplasia (BPH). One hundred thirteen
      patients (mean age 70.8 years) were enrolled. All patients met BPH clinical study
      guidelines. Seven agents were utilized:tamsulosin 0.2mg, silodosin 8mg, urapidil
      60mg, naftopidil 50mg, prazosin 1mg, terazosin 2mg, and doxazosin 1mg. Patients
      were initially prescribed tamsulosin or silodosin for a week and then urapidil
      for a week. Two weeks later, they were prescribed the better of the 2 agents for
      a week and a new agent for the next week. This cycle was repeated until all 7
      agents were tested. Efficacy was evaluated with the International Prostate
      Symptom Score. The agent rankings were doxazosin (25 [22%]), silodosin (22
      [19%]), urapidil (19 [17%]), naftopidil (17 [15%]), terazosin (12 [11%]),
      tamsulosin (11 [10%]), prazosin (7 [6%]). Only 12 patients (11%) changed agents
      after the crossover study was completed. The major reason was adverse events
      (83%). We found that each of the 7 alpha1AR antagonists has its own supporters.
      Further, the one-week crossover study was useful in identifying the best agent
      for the treatment of each individual with LUTS. 

PMID- 23970324
TI  - Septic pulmonary embolism induced by dental infection.
AB  - Dental infection can be an important source for septic pulmonary embolism (SPE),
      but only a few cases of SPE accompanying dental infection have been reported. The
      aim of this study was to characterize the clinical features of SPE induced by
      dental infection. Patients who fulfilled the diagnostic criteria described in the
      text were recruited in a retrospective fashion. All 9 patients were men, with a
      median age of 59 years (range:47 to 74 years). Eight patients had chest pain
      (88.9%), 5 had a preceding toothache (55.6%) and 3 had preceding gingival
      swelling (33.3%). Blood cultures obtained from 7 patients were negative.
      Periodontitis was found in all of the cases, periapical periodontitis in 5 cases,
      and gingival abscess in 3 cases. The median duration of hospitalization was 15
      days, and symptoms were mild in some cases. In addition to antimicrobial therapy,
      tooth extraction was performed in 3 cases, tooth scaling in 6. SPE induced by
      dental infection has prominent clinical characteristics such as male
      preponderance, chest pain, preceding toothache, and mild clinical course. 

PMID- 23970325
TI  - "Hook and roll technique" using an articulating hook cautery to provide a
      critical view during single-incision laparoscopic cholecystectomy.
AB  - We describe a new simple and easy technique called the "Hook and roll technique"
      (HRT) that uses an articulating hook cautery to provide a critical view during
      single incision laparoscopic cholecystectomy (SILC). A 2-cm incision is made at
      the umbilicus to insert three 5-mm trocars or a multichannel port. After
      dissection of the serosa of the dorsal and ventral sides of the gall bladder,
      including Calot's triangle, the angled tip of the hook cautery is inserted
      between the cystic artery and duct with its tip placed dorsally. The tip is then
      rotated in a clockwise manner to avoid bile duct injury, allowing the connective
      tissue between them to be hooked, coagulated and cut. This procedure is repeated
      several times, followed by dissection between the cystic artery and the liver bed
      to achieve a critical view. From December 2008 to May 2011, 121 patients
      underwent SILC using HRT in our hospital without any serious complications. This
      technique is suitable for SILC, as it is consists of simple procedures that can
      be performed safely and easily, even by left hand in a cross-over approach, and
      it allows complete dissection of Calot's triangle to achieve a critical view
      without using any dissector under dangerous in-line viewing. 

PMID- 23970326
TI  - Large ulceration of the oropharynx induced by methotrexate-associated
      lymphoproliferative disorders.
AB  - We present a case of a 67-year-old Japanese man with a serious oropharyngeal
      ulceration that at first seemed to be destructive malignant lymphoma or
      oropharyngeal carcinoma. We suspected methotrexate (MTX)-associated
      lymphoproliferative disorder (LPD) induced by MTX treatment for rheumatoid
      arthritis (RA). About 3 weeks after simple discontinuation of MTX, complete
      regression of the disease was observed, confirming our diagnosis. 

PMID- 23970327
TI  - Negative pressure wound therapy incorporating early exercise therapy in hand
      surgery: bag-type negative pressure wound therapy.
AB  - In the postoperative treatment of hand surgery, it is important to start exercise
      therapy as early as possible. In conventional negative pressure wound therapy,
      the fingers are immobilized by the film dressing covering the wound and hand,
      thereby preventing sufficient rehabilitation. Here, we devised a bag-type
      negative pressure wound therapy that makes it possible to start finger exercises
      almost immediately, and we applied it to 4 patients:one each with hand burns,
      symmetrical peripheral gangrene, a crush injury accompanied by extensive skin
      defects and a fingertip degloving injury. The duration of the bag-type negative
      pressure wound therapy ranged from three to eight weeks, and good granulation was
      achieved, so that a skin graft was not required. In addition, particularly in the
      case of the fingertip degloving injury, good nail regeneration was achieved.
      Except for the case of symmetrical peripheral gangrene, a good range of joint
      motion with a percent total active motion (%TAM) of 94.7% or more was achieved.
      Our therapy was performed by inserting the hand into a sealing bag;sufficient
      exercise therapy was made possible by expanding the bag during rehabilitation. 

PMID- 23970328
TI  - Economical, green and dual-function pyridyl iodides as electrolyte components for
      high efficiency dye-sensitized solar cells.
AB  - Pyridyl iodides were synthesized to serve as effective, economical, green and
      dual function additives for high efficiency and stable DSCs. Using commercial P25
      as the photoanode, a high PCE of 7.81% was achieved with a pyridyl iodide
      containing electrolyte. Meanwhile, DSCs based on our novel electrolytes
      demonstrated better stability. 

PMID- 23970329
TI  - Probing the acetylation code of histone H4.
AB  - Histone modifications play crucial roles in genome regulation with lysine
      acetylation being implicated in transcriptional control. Here we report a
      proteome-wide investigation of the acetylation-dependent protein-protein
      interactions of the N-terminal tail of histone H4. Quantitative peptide-based
      affinity MS experiments using the SILAC approach determined the interactomes of
      H4 tails monoacetylated at the four known acetylation sites K5, K8, K12, and K16,
      bis-acetylated at K5/K12, triple-acetylated at K8/12/16 and fully tetra
      acetylated. A set of 29 proteins was found enriched on the fully acetylated H4
      tail while specific binders of the mono and bis-acetylated tails were barely
      detectable. These observations are in good agreement with earlier reports
      indicating that the H4 acetylation state establishes its regulatory effects in a
      cumulative manner rather than via site-specific recruitment of regulatory
      proteins.

PMID- 23970330
TI  - Restraint and seclusion: the perspective of service users and staff members.
AB  - BACKGROUND: Restrictive measures may have important physical and psychological
      consequences on all persons involved. The current study examined how these are
      perceived by persons with intellectual disabilities and staff. MATERIALS AND
      METHODS: Interviews were conducted with eight persons with intellectual
      disabilities who experienced a restrictive measure and their care providers. They
      were queried on their understanding of the restrictive measure, its impact on the
      relationship, their emotions and alternative interventions. RESULTS: Restrictive
      measures were experienced negatively by persons with intellectual disabilities
      and their care providers. Service users reported feeling sad and angry, whereas
      staff mentioned feeling anxious. Moreover, persons with intellectual disabilities
      appeared to understand the goal of restrictive measures (e.g. ensuring their own
      and others' safety) and identified alternative interventions (e.g. speaking with
      a staff member or taking a walk). CONCLUSION: This study sheds further light on
      how persons with intellectual disabilities and staff experience the application
      of restrictive measures. Debriefing sessions with service users and staff may
      help minimize negative consequences.

PMID- 23970331
TI  - 3-nitrotyrosine, a biomarker for cardiomyocyte apoptosis induced by diabetic
      cardiomyopathy in a rat model.
AB  - The aim of this study was to investigate whether 3-nitrotyrosine (3-NT) may serve
      as a predictive biomarker for cardiomyocyte apoptosis in a diabetic
      cardiomyopathic rat model. Using male Sprague-Dawley (SD) rats in a prospective,
      randomized, controlled study, a diabetic type II animal model was established by
      injection with streptozotocin. The diabetic group and the diabetic cardiomyopathy
      (DCM) group were administered valsartan. This study revealed the following: i)
      The ratio of heart/body weight increased in the DCM, diabetes administered with
      valsartan (D+V) and DCM+V groups compared with the N group. ii) The expression
      index (EI) of 3-NT correlated positively with the apoptotic index (AI) of the
      cardiomyocytes, whereas 3-NT in the serum did not reflect changes in the AI. iii)
      The AI of the DCM group was the highest of the assessed groups. The AI of the DCM
      group was higher than that in the D+V group, and the AI of the DCM+V group was
      higher than that of the N group. iv) The EI of 3-NT increased with a higher AI.
      The higher the EI of 3-NT, the higher the AI observed in rat cardiomyocytes. Both
      the EI of 3-NT and the AI of the DCM group were higher than in the other groups.
      However, both the EI of 3-NT and the AI in the DCM group markedly decreased for
      the DCM+V group. 3-NT in the myocardial tissue of rats was deemed to be a
      successful biomarker for predicting cardiomyocyte apoptosis in SD rats. 3-NT
      levels were significantly increased and related to cardiomyocyte apoptosis.
      Valsartan post-treatment reversed the increase of 3-NT and apoptosis in diabetic
      cardiomyopathy.

PMID- 23970332
TI  - Regulation of differentiation in trabecular bone-derived mesenchymal stem cells
      by T cell activation and inflammation.
AB  - Mesenchymal stem cells (MSCs) are multipotent stem cells with the ability to
      migrate to sites of inflammation and injury, where they participate in tissue
      regeneration and repair. The present study aimed to investigate the effects of T
      cell activation and inflammation on the differentiation of MSCs. Human trabecular
      bone-derived MSCs were isolated from patients undergoing total hip replacement,
      and T cells were isolated and purified from peripheral blood mononuclear cells
      (PBMCs) using CD3 MicroBeads. MSCs were co-cultured with activated T cells to
      mimic the inflammatory microenvironment. MTS assay was used to detect cell
      proliferation.qRT-PCR, western blotting, histology and immunohistochemical
      staining were used to detect the adipo-/osteo-specific gene expression and the
      relative signaling pathway. The MTS results showed that higher concentrations of
      T cells significantly increased the proliferation of MSCs. Expression of the
      inflammatory gene IL-6 was upregulated, while expression of IL-10 and INFgamma
      was downregulated in MSCs exposed to activated T cells. The results also showed
      that PHA-activated T cells significantly upregulated the expression of PPARgamma
      and FABP4 (adipo-specific genes) in MSCs, but no difference was noted in the
      expression of RUNX2, osteocalcin and ALP (osteo-specific genes) at the protein
      level. T cell treatment and inflammation inhibited the protein expression of TGF
      beta1 and the phosphorylation of Smad3, resulting in the weakening of the TGF
      beta/Smad pathway and enhancing the adipogenic differentiation of MSCs. The
      results indicated that PHA-activated T cells and inflammation could promote
      adipogenesis without affecting the late stage of osteogenesis of MSCs, by
      increasing the expression of key adipogenic genes through TGF-beta/Smad3
      signaling. 

PMID- 23970333
TI  - p53 restoration can overcome cisplatin resistance through inhibition of Akt as
      well as induction of Bax.
AB  - Cisplatin (CDDP) is a chemotherapeutic agent that is widely used to treat many
      cancers. However, initial resistance to CDDP is a serious problem in treating
      cancers. In this study, in order to develop an approach to overcome resistance to
      CDDP, we investigated the difference in apoptotic processes between CDDP
      sensitive cells and CDDP-resistant cells. By screening with CDDP sensitivity
      tests, we chose SNU-16 cells which are relatively resistant to CDDP, and SNU-1
      cells which are sensitive to CDDP. We compared the difference between the two
      cell lines focusing on apoptosis. CDDP-induced reactive oxygen species (ROS)
      generation significantly induced loss of mitochondrial membrane potential (MMP,
      ?Psim) in SNU-1 cells, but not in SNU-16 cells. In addition, the ratio of Bax to
      Bcl-2 was increased by CDDP treatment in SNU-1 cells, but not in SNU-16 cells. To
      augment the loss of MMP, ?Psim in SNU-16, we inhibited Akt activity of SNU-16
      cells to suppress their anti-apoptotic activity. The inhibition of Akt activity
      led to suppression of the anti-apoptotic protein XIAP. Akt inhibition slightly
      enhanced CDDP-induced apoptosis in SNU-16 cells. In addition, we enhanced pro
      apoptotic activity by transfecting the cells with the wild-type p53 gene. The
      induction of wild-type p53 can enhance CDDP-induced apoptosis not only by
      inducing Bax protein but also by suppressing anti-apoptotic proteins through
      inhibition of Akt. In conclusion, this study suggests that the primary
      contributor to resistance to CDDP in SNU-16 cells may well be a failure of
      induction of apoptosis due to a lack of induction of pro-apoptotic proteins
      rather than suppression of anti-apoptotic proteins, and that restoration of p53
      function can overcome the resistance to CDDP not only by augmenting the pro
      apoptotic drive through p53-mediated transcriptional activation but also by
      inhibiting the anti-apoptotic drive through inhibition of Akt activity. 

PMID- 23970334
TI  - Rapid dielectrophoretic characterization of single cells using the
      dielectrophoretic spring.
AB  - Dielectrophoresis-based cell separation has significant promise for separation of
      cells from heterogeneous mixtures based on their electrical properties and is
      used in diverse areas ranging from hematopoietic stem cell purification to cancer
      cell isolation. The electrical properties of cells in heterogeneous populations
      determine if and how well cell subpopulations are separable, and therefore the
      utility of dielectrophoretic separation is fundamentally determined by our
      ability to measure electrical properties of cell populations on a cell-by-cell
      basis. We developed an automated system for electrical characterization of cells
      that can characterize 1000's of individual cells across a range of conditions
      (>30 conditions/h). The system uses a continuous-flow microfluidic device and a
      method termed the dielectrophoretic spring that uses the force balance between
      dielectrophoresis and fluid drag to measure electrical properties of cells
      independent of size. We present characterization of the method with beads and
      cells as well as its application to rapidly find conditions that can discriminate
      neutrophils with different activation states. 

PMID- 23970335
TI  - Recurrent miscarriage: do professionals adhere to their guidelines.
AB  - STUDY QUESTION: Is the actual care for recurrent miscarriage in clinical practice
      in accordance with 23 guideline-based quality indicators? SUMMARY ANSWER: The
      accordance of actual care with the guidelines was poor and there is evident room
      for improvement. WHAT IS KNOWN ALREADY: Evidence-based guidelines are important
      instruments to improve quality of care, but implementation of guidelines is often
      problematic. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study was
      performed within a 12-month period (2006) in nine departments of Obstetrics and
      Gynaecology in the Netherlands. PARTICIPANTS, SETTING, METHODS: Five hundred and
      thirty women with recurrent miscarriage were included. Actual care was assessed
      with 23 guideline-based quality indicators (covering diagnostics, therapy and
      counselling) by calculating per indicator the percentage of women for whom the
      indicator was followed. Thereafter we did multilevel analyses, to relate the
      adherence to the indicator to determinants of women, professionals and hospitals.
      MAIN RESULTS AND THE ROLE OF CHANCE: Homocysteine and antiphospholipid antibodies
      were determined in 39 and 47%, respectively. Thrombophilia screening (54%) and
      karyotyping (50%) were offered to women regardless of their underlying risk for
      inherited thrombophilia or chromosome abnormalities. Higher maternal age at the
      time of presentation and a lower number of preceding miscarriages were improperly
      used to decide on diagnostic tests and were both associated with lower guideline
      adherence by professionals. Professionals with a subspecialization in recurrent
      miscarriage performed better standard care, i.e. screening for antiphospholipid
      antibodies and homocysteine, but also showed overuse of diagnostics in women at
      low risk of inherited thrombophilia. LIMITATIONS, REASONS FOR CAUTION:
      Retrospective cohort study. WIDER IMPLICATIONS OF THE FINDINGS: Quality
      indicators used will enable measurement of quality of care. STUDY FUNDING: The
      study was funded by The Netherlands Organisation for Health Research and
      Development (ZonMw) (Grant no. 94517005). None of the authors has any conflict of
      interest to declare.

PMID- 23970336
TI  - Self-assembly cavitand precisely recognizing hexafluorosilicate: a concerted
      action of two coordination and twelve CH...F bonds.
AB  - Bis-pyridazine tectons support the structure of metallosupramolecular cavitand
      Cu2L4(4+), which is capable of selective encapsulation of SiF6(2-) anions by a
      set of multiple host-guest interactions.

PMID- 23970337
TI  - Evaluation of retinal nerve fiber layer thickness measurements for glaucoma
      detection: GDx ECC versus spectral-domain OCT.
AB  - BACKGROUND: To assess the ability of retinal nerve fiber layer (RNFL) thickness
      measurements obtained using GDx-enhanced corneal compensation (ECC) or spectral
      domain optical coherence tomography (RTVue), and that of ganglion cell complex
      (GCC) scan available on RTVue, to detect glaucoma. METHODS: One randomly selected
      eye of 205 subjects (70 normal, 65 ocular hypertension, and 70 glaucoma)
      underwent a complete clinical and instrumental examination. RTVue spectral-domain
      optical coherence tomography was used to assess RNFL thickness and GCC
      parameters, GDx ECC to assess RNFL thickness. Areas under the receiver operating
      characteristic curves (AUCs) and sensitivity of the RNFL and GCC parameters were
      calculated at a fixed specificity of 95%, and the diagnostic abilities of the
      RNFL values obtained using the 2 instruments were compared. We also compared the
      results obtained in the normal, ocular hypertensive, and glaucomatous subjects.
      RESULTS: Best GDx RNFL parameter was nerve fiber indicator (NFI) (AUC 0.99,
      sensitivity 96%); the best RTVue parameters were average (AUC 0.98, sensitivity
      90%), inferior-temporal (AUC 0.97, sensitivity 89%), and superior-temporal RNFL
      thickness (AUC 0.96, sensitivity 87%). There were no significant differences
      between the 2 devices (P>0.05). Best GCC parameters were focal loss volume (AUC
      0.98, sensitivity 91%) and global loss volume (AUC 0.96, sensitivity 87%).
      CONCLUSIONS: GDx ECC and RTVue show a very good diagnostic ability to detect
      glaucoma. Most of the RNFL parameters had high AUCs and sensitivities. The
      diagnostic validity of GCC was comparable with that of the RNFL parameters, and
      they may be very useful in detecting RNFL damage.

PMID- 23970338
TI  - Factors determining the peripapillary retinal nerve fiber distribution.
AB  - PURPOSE: To evaluate the influence of the arrangement of the retinal vessels and
      other ocular features on the peripapillary retinal nerve fiber layer (RNFL)
      distribution. METHODS: Fifty normal eyes were included in the study. Axial length
      (AL), spherical equivalent of the refractive error, and central corneal thickness
      (CCT) were measured. The interpeak distance of the peripapillary RNFL thickness;
      the angle between the superior temporal (ST) and inferior temporal (IT) retinal
      veins; and the average peripapillary RNFL thickness were obtained from the
      printout results of the spectral-domain optical coherence tomography. The
      distance from the optic disc center to the foveola and the ratio of distance to
      disc width were measured from fundus photographs. All measurements were evaluated
      for correlations among one another and multiple regression analysis and factor
      analysis was used to determine how ocular factors independently related to the
      RNFL distribution. RESULTS: As the AL became longer (P=0.033), and the angle
      between the ST and IT veins became smaller (P<0.001), the 2 peaks of the
      peripapillary RNFL thickness moved farther apart. In multiple regression
      analysis, angle between the ST and IT veins (beta=-0.587, P<0.001) and CCT (beta=
      0.275, P=0.011) were significantly related to interpeak distance of the
      peripapillary RNFL. CONCLUSIONS: Decreasing angle between the IT and ST veins,
      thinner CCT, and increasing AL all appeared to increase the separation of the
      RNFL peaks. Inter-vessel polar angle affected more on determining the location of
      the peak in RNFL thickness map. These factors might be used to optimize normative
      data of the peripapillary RNFL.

PMID- 23970339
TI  - Retinal nerve fiber layer volume measurements in healthy subjects using spectral
      domain optical coherence tomography.
AB  - PURPOSE: To report retinal nerve fiber layer (RNFL) volume measurement using
      spectral domain optical coherence tomography (SD-OCT). We determined the
      characteristics and effecting factors of the RNFL volume in healthy eyes.
      METHODS: Eighty-six eyes from 86 healthy volunteers were included. All
      participants underwent 3D-disc scanning using SD-OCT. We developed a computer
      program using Matlab software to extract RNFL thickness values from colored
      topographic RNFL thickness map. Total average, quadrant, and clock-hour RNFL
      volume were automatically calculated between 2.5 and 5 mm diameter circles using
      the length, width, and height of each pixel derived from the RNFL thickness map.
      RESULTS: The mean total RNFL volume was 1.478+/-0.124 mm and RNFL volume profiles
      showed double-hump patterns. RNFL volumes of superior and inferior quadrants were
      significantly greater than those of temporal and nasal quadrants (all P<0.001). A
      strong correlation existed between RNFL volume and conventional circumpapillary
      RNFL thickness measured by built-in software (R=0.895 to 0.972). Image quality
      and age were associated with RNFL volume measurement. CONCLUSIONS: RNFL volume
      measurement from RNFL thickness map analysis provides an alternative approach to
      characterizing and evaluating RNFL. RNFL volume measurement may be valuable for
      the objective and quantitative evaluation of 3-dimensional RFNL changes.

PMID- 23970340
TI  - Functional pituitary tumors masquerading as primary glaucoma and effect of
      hypophysectomy on intraocular tension.
AB  - We report 2 bilateral cases that presented as primary ocular hypertension and
      primary angle-closure glaucoma, respectively; however, they were subsequently
      discovered to be harboring secretory pituitary tumors. After transsphenoidal
      tumor resection, intraocular pressures (IOPs) in all 4 eyes returned to normal
      levels. Sudden rise in IOP then again served as a primary manifestation of
      relapse in the second patient with growth hormone secreting pituitary tumor. It
      was not found feasible for resurgery; thus, patient needed trabeculectomy in both
      eyes to achieve an optimum control of intraocular tension. We conclude that
      pituitary adenomas may mimic primary glaucoma without producing vertical
      hemianopia and cause a reversible rise in IOP. Furthermore, a careful ongoing
      expert ophthalmologic assessment may serve as a useful clinical marker for early
      relapse in these tumors. 

PMID- 23970341
TI  - Quantitative analysis of localized retinal nerve fiber layer defects using
      spectral domain optical coherence tomography.
AB  - PURPOSE: To compare the topographic features of localized retinal nerve fiber
      layer (RNFL) defects presented in red-free RNFL photography and spectral domain
      optical coherence tomography (SD-OCT), and to evaluate the correlation with
      structural and functional parameters. METHODS: Sixty eyes with localized RNFL
      defects in red-free RNFL photographs were included. RNFL thickness map and
      significance map were obtained by SD-OCT. The angular location, angular width,
      and area of localized RNFL defects were measured and compared among RNFL
      thickness map, significance map (red, <1% level; yellow, <5% level), and RNFL
      photograph. The RNFL defect areas were analyzed by their correlations with
      structural and functional parameters. RESULTS: The RNFL defect area of RNFL
      thickness map was significantly greater than those of red significance map, and
      smaller than those of RNFL photograph and yellow significance map (all P<0.001).
      RNFL thickness map showed a significantly narrower angular width than RNFL
      photograph and yellow significance map (all P<0.001). The area, angular width,
      and angular location of localized RNFL defects in RNFL photographs strongly
      correlated with those of RNFL thickness maps and significance maps (all r>=0.741,
      P<0.001). The relationship between RNFL defect area and structural-functional
      parameters was also significant. CONCLUSIONS: The high topographic correlations
      in RNFL defects between RNFL photography and SD-OCT RNFL maps suggest the
      validity of SD-OCT RNFL imaging for detecting localized glaucomatous RNFL damage.
      In addition, structural and functional parameters are closely related to RNFL
      defect areas. Quantitative measurements of RNFL defects might be valuable for
      glaucoma diagnosis.

PMID- 23970342
TI  - Abiotrophia defectiva bleb-associated endophthalmitis confirmed with 16s
      ribosomal RNA sequencing.
AB  - One recognized complication of trabeculectomy with visually devastating potential
      is blebitis. We present a case of a 74-year-old woman with a culture and
      polymerase chain reaction-positive Abiotrophia defectiva bleb-associated
      endophthalmitis. Abiotrophia defectiva is a rare but possible cause of
      endophthalmitis secondary to blebitis and should be considered in culture
      negative cases. Prompt identification, hence directed eradication, of the
      causative organism in such visually threatening cases may be facilitated by
      requesting polymerase chain reaction and 16S ribosomal RNA sequencing. 

PMID- 23970344
TI  - Changes in working conditions and subsequent sickness absence.
AB  - OBJECTIVES: The aim of the study was to examine the associations of changes in
      exposure to physical and psychosocial working conditions on subsequent sickness
      absence among ageing municipal employees of the City of Helsinki, Finland.
      METHODS: Changes in exposure to working conditions were assessed between baseline
      (2000-2002) and follow-up (2007) surveys. Register-based sickness absence
      information was linked to the survey data (N=3739) and followed-up from the
      return of the questionnaire in 2007 to the end of 2010. The study included six
      measures of physical and two measures of psychosocial working conditions.
      Negative binomial regression analysis was used to assess the associations and
      adjust for covariates. RESULTS: Favorable changes in physical working conditions
      lowered the risk for sickness absence whereas adverse changes increased the risk.
      Adverse changes in psychosocial working conditions only slightly increased the
      risk for sickness absence whereas favorable changes were unassociated with
      sickness absence. CONCLUSIONS: Changes in exposure to physical working conditions
      in particular are associated with subsequent sickness absence. Preventing an
      increase in exposure to both psychosocial and physical working conditions and
      promoting a decrease in exposure to physical working conditions likely helps
      reduce the risk of sickness absence.

PMID- 23970345
TI  - Progesterone protects ovarian cancer cells from cisplatin-induced inhibitory
      effects through progesterone receptor membrane component 1/2 as well as AKT
      signaling.
AB  - Progesterone, also known as P4 (pregn-4-ene-3, 20-dione), is a C-21 steroid
      hormone involved in the female menstrual cycle, pregnancy (supports gestation)
      and embryogenesis of humans and other species. Despite the physiological effects,
      P4 is also effective for the treatment of numerous pathological states, such as
      multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus as well
      as cancer. Considering the hormone microenvironment of gynecological cancers, P4
      should be particularly noted in ovarian cancer. The present study demonstrated
      that P4 protected the ovarian cancer cell line HO-8910 from cisplatin (CDDP)
      induced cell cycle arrest and restored the cell migratory capability following
      treatment of CDDP. Mechanistically, both progesterone receptor membrane component
      1 (PGRMC1) and the progesterone receptor (PGR) were decreased in the cells
      treated with CDDP plus P4, while the level of progesterone receptor membrane
      component 2 (PGRMC2) was significantly elevated. Reversely, in the HO-8910 cells
      treated with CDDP alone, levels of both PGRMC1 and PGR were increased while the
      level of PGRMC2 was decreased. In addition to the receptor expression profile,
      the PI3K/AKT signaling pathway was also involved in the action of P4 in the CDDP
      resistant HO-8910 cells, and a chemical inhibitor for PI3K, LY294002,
      significantly abolished the anti-apoptotic effect of P4. Consequently, the
      addition of a PI3K inhibitor to CDDP-based chemotherapy may have a more
      beneficial application for ovarian cancer therapy. 

PMID- 23970346
TI  - Visualizing cellular machines with colocalization single molecule microscopy.
AB  - Many of the cell's macromolecular machines contain multiple components that
      transiently associate with one another. This compositional and dynamic complexity
      presents a challenge for understanding how these machines are constructed and
      function. Colocalization single molecule spectroscopy enables simultaneous
      observation of individual components of these machines in real-time and grants a
      unique window into processes that are typically obscured in ensemble assays.
      Colocalization experiments can yield valuable information about assembly
      pathways, compositional heterogeneity, and kinetics that together contribute to
      the development of richly detailed reaction mechanisms. This review focuses on
      recent advances in colocalization single molecule spectroscopy and how this
      technique has been applied to enhance our understanding of transcription, RNA
      splicing, and translation. 

PMID- 23970347
TI  - Predominant role of vasoconstrictors over dilatators derived from arachidonic
      acid in hypoxic pulmonary vasoconstriction.
AB  - Prostanoids derived from arachidonic acid (AA) have been shown to play a
      permissive role in the regulation of vascular tone and wall tension.
      Conventionally, epoxyeicosatrienoic acids (EETs) and prostacyclin have been
      considered as dilatators, whereas thromboxane (TX) and hydroxyeicosatetraenoic
      acid (HETE) were considered as vasoconstrictors. However, the role of these
      prostanoids in the mediation of acute hypoxic pulmonary vasoconstriction is not
      yet clearly understood. In the present study, the role of prostanoids in the
      acute hypoxic response in rat isolated intrapulmonary arteries (IPAs) was
      investigated. Exogenous AA directly caused vasoconstriction, but exerted a
      significant inhibition on hypoxic vasoconstriction. The vasoconstriction by AA
      was mediated by the endothelium. AA metabolites from lipoxygenase (LOX) had no
      effect on vascular tone or hypoxic vasoconstriction. Consistent results from the
      blockage of cytochrome P450 (CYP) or CYP epoxide hydrolase showed that HETE
      contributed to endothelium-independent hypoxic vasoconstriction. EET via
      epoxygenase exerted no effect on 80 mM KPSS-induced vessel contraction or hypoxic
      vasoconstriction. In addition, prostacyclin also failed to inhibit hypoxic
      pulmonary vasoconstriction (HPV). However, blockage of thromboxane A2/prostanoid
      (TP) receptors almost eliminated hypoxic vasoconstriction, suggesting the primary
      role of TP receptors in the regulation of the hypoxic response in rat IPAs. In
      conclusion, the current data indicate the predominant role of vasoconstrictors
      instead of dilatators in mediating HPV. These data also highlight a pivotal role
      for voltage-independent Ca2+ entry in pulmonary hypoxic response and suggest that
      modulation of these channels by prostanoids underlies their regulatory
      mechanisms.

PMID- 23970348
TI  - Effects of gamma-synuclein on the tumorigenicity and metastasis of colon cancer
      SW1116 cells in vitro and in vivo.
AB  - Recent evidence suggests the involvement of gamma-synuclein in tumorigenesis and
      tumor progression. The present study was designed to further clarify the effects
      of gamma-synuclein on the biological features of colon cancer cells in vitro and
      in vivo. We constructed the eukaryotic expression vector and siRNA vector and
      selected stable transfectants to respectively upregulate and downregulate gamma
      synuclein expression in SW1116 cells. we found that silencing of gamma-synuclein
      significantly attenuated SW1116 cell growth and colony formation in vitro
      (P<0.05), and overexpression of gamma-synuclein moderately enhanced cell growth
      and colony formation, but not significantly when compared with the parental
      SW1116 cells and empty vector-transfected cells (P>0.05). Meanwhile,
      overexpression of gamma-synuclein significantly facilitated SW1116 cell
      migration, invasion and adhesion to human liver sinusoidal endothelial cells
      (HLSECs) in vitro (P<0.05), and the effects were less attenuated by gamma
      synuclein knockdown (P>0.05). Furthermore, gamma-synuclein promoted these
      malignant phenotypes in a gamma-synuclein expression quantity-dependent manner
      not only in vitro but also in the in vivo expression. stable cells were injected
      subcutaneously into the right flank, and injected intrasplenically in nude mice.
      gamma-synuclein knockdown suppressed the tumorigenicity of SW1116 cells in mice,
      which presented significantly smaller tumor masses on day 6 over a 30-day period,
      compared with empty vector cells (P<0.05). Meanwhile, overexpression of gamma
      synuclein led to a profound augmentation of liver metastasis in nude mice, not
      only in macroscopic appearance but also in the size and weight of livers
      (P<0.05). These results provide strong evidence that suggests gamma-synuclein
      plays a positive role in the progression of colorectal cancer. 

PMID- 23970349
TI  - 8-bromo-5-hydroxy-7-methoxychrysin targeting for inhibition of the properties of
      liver cancer stem cells by modulation of Twist signaling.
AB  - Emerging evidence has suggested that cancer stem cells with expression of surface
      biomarkers including CD133 and CD44 have more aggressive biological behavior,
      including epithelial-mesenchymal transition (EMT), which are closely related to
      invasion. The upregulation and nuclear relocation of the EMT regulator Twist1
      have been implicated in the tumor invasion and metastasis of human hepatocellular
      carcinoma (HCC). In this study, we aimed to isolate and characterize a small
      population of CD133+ cells that existed in the HCC cell line SMMC-7721 by MACS
      and investigated the possible roles of 8-bromo-7-methoxychrysin (BrMC), a
      synthetic analogue of chrysin, in inhibiting the properties of CD133+ sphere
      forming cells (SFCs) derived from the HCC cell line SMMC-7721, namely liver
      cancer stem cells (LCSCs). Based on the data, BrMC inhibited the proliferation,
      self-renewal and invasion of LCSCs in vitro and in vivo, downregulated the
      expression of the LCSC biomarkers CD133 and CD44 and induced EMT by
      downregulating the expression of Twist and beta-catenin in LCSCs. BrMC
      potentiated the inhibition of LCSCs self-renewal after reduction of twist protein
      levels, which was attenuated when twist was overexpressed. This study not only
      provides an important experimental and theoretical basis for investigation of
      BrMC in LCSCs, but also helps in the development of effective therapeutic
      medicine for HCC.

PMID- 23970350
TI  - A novel approach to quantifying ciliary physiology: microfluidic mixing driven by
      a ciliated biological surface.
AB  - From the lungs to the central nervous system, cilia-driven fluid flow plays a
      fundamental role in many facets of life. Yet, there are few quantitative methods
      for analysing the function of ciliated surfaces. Here, we report a novel
      microfluidic approach for quantifying the performance of a ciliated surface using
      mixing performance as an integrated readout. 

PMID- 23970351
TI  - One inositol ring to rule thrombosis.
AB  - In this issue of Blood, Ghosh and colleagues report that knocking out an inositol
      kinase in mice diminishes polyphosphate in platelet dense granules, thereby
      reducing hemostasis and protecting against thrombosis.

PMID- 23970352
TI  - Transplants for the elderly in myeloma.
AB  - In this issue of Blood, Gay et al provide important new information that can be
      used to design future phase 3 trials.

PMID- 23970353
TI  - Precision 're'arming of CD33 antibodies.
AB  - In this issue of Blood, Kung Sutherland et al report on the preclinical activity
      of SGN-CD33A, a humanized anti-CD33 antibody conjugated to a
      pyrrolobenzodiazepine (PBD) dimer via a protease-cleavable linker, against acute
      myeloid leukemia (AML) cells in vitro and in vivo.

PMID- 23970354
TI  - A mouse model of hemolytic disease of the newborn.
AB  - In this issue of Blood, Stowell et al describe a novel mouse model of hemolytic
      disease of the fetus and newborn (HDFN) that recapitulates many of the key
      features of human disease.1 Recently, this same group of researchers described a
      transgenic mouse that expresses the human KEL2 (Chellano) red cell surface
      protein from the Kell system on red cells, and subsequently demonstrated that
      Kell differences on transfused blood induce antibody responses and hemolytic
      transfusion reactions similar to those seen in patients. In this latest report,
      Stowell et al demonstrate that similar to some patients, Kell differences between
      mother and father can lead to maternal antibody generation and hemolytic disease
      in utero. In so doing, they provide experimental confirmation of a long sought
      after animal model of HDFN.

PMID- 23970355
TI  - Paneth cells in gut GVHD: a Panglossian perspective.
AB  - In this issue of Blood, Levine et al present an intriguing analysis highlighting
      the potential clinical impact of Paneth cell loss in gastrointestinal (GI) acute
      graft-versus-host disease (GVHD).

PMID- 23970356
TI  - PRCP regulates angiogenesis in vivo.
AB  - In this issue of Blood, Adams et al provide evidence for an important novel
      function of prolylcarboxypeptidase (PRCP), or angiotensinase C, in endothelial
      cell physiology and angiogenesis.

PMID- 23970357
TI  - Ionic liquids showing phase separation with water prepared by mixing hydrophilic
      and polar amino acid ionic liquids.
AB  - Both water soluble lysine- and aspartic acid-based amino acid ionic liquids
      (AAILs) were mixed to prepare polar AAILs showing phase separation with water. 

PMID- 23970358
TI  - Williams' paradox and the role of phenotypic plasticity in sexual systems.
AB  - As George Williams pointed out in 1975, although evolutionary explanations, based
      on selection acting on individuals, have been developed for the advantages of
      simultaneous hermaphroditism, sequential hermaphroditism and gonochorism, none of
      these evolutionary explanations adequately explains the current distribution of
      these sexual systems within the Metazoa (Williams' Paradox). As Williams further
      pointed out, the current distribution of sexual systems is explained largely by
      phylogeny. Since 1975, we have made a great deal of empirical and theoretical
      progress in understanding sexual systems. However, we still lack a theory that
      explains the current distribution of sexual systems in animals and we do not
      understand the evolutionary transitions between hermaphroditism and gonochorism.
      Empirical data, collected over the past 40 years, demonstrate that gender may
      have more phenotypic plasticity than was previously realized. We know that not
      only sequential hermaphrodites, but also simultaneous hermaphrodites have
      phenotypic plasticity that alters sex allocation in response to social and
      environmental conditions. A focus on phenotypic plasticity suggests that one sees
      a continuum in animals between genetically determined gonochorism on the one hand
      and simultaneous hermaphroditism on the other, with various types of sequential
      hermaphroditism and environmental sex determination as points along the spectrum.
      Here I suggest that perhaps the reason we have been unable to resolve Williams'
      Paradox is because the problem was not correctly framed. First, because, for
      example, simultaneous hermaphroditism provides reproductive assurance or dioecy
      ensures outcrossing does not mean that there are no other evolutionary paths that
      can provide adaptive responses to those selective pressures. Second, perhaps the
      question we need to ask is: What selective forces favor increased versus reduced
      phenotypic plasticity in gender expression? It is time to begin to look at the
      question of sexual system as one of understanding the timing and degree of
      phenotypic plasticity in gender expression in the life history in terms of
      selection acting on a continuum, rather than on a set of discrete sexual systems.

PMID- 23970360
TI  - Inhibitory effect of dsRNA TLR3 agonist in a rat hepatocellular carcinoma model.
AB  - Hepatocellular carcinoma (HCC) is one of the most common types of malignant
      tumor. Studies have demonstrated that the toll-like receptor 3 (TLR3)/interferon
      pathway is inhibitory in cancer cell proliferation, suggesting that the
      activation of this pathway may have therapeutic potential. In the present study,
      the inhibitory effects of BM-06, a double-stranded (ds)RNA TLR3 agonist, against
      HCC were studied in vivo. Using a 2-acetylaminofluorene-induced HCC rat model,
      histological examination and analysis of corresponding biomarkers following
      treatment with BM-06, showed a decrease in tumor growth and cell proliferation,
      and an increase in apoptosis compared with that in a phosphate-buffered saline
      control group. In addition, the observed antitumor effect of BM-06 in the HCC rat
      model was demonstrated to be superior to the known TLR3 agonist, polyinosinic
      polycytidylic acid.

PMID- 23970361
TI  - APC germline mutations in families with familial adenomatous polyposis.
AB  - Adenomatous polyposis coli (APC) germline mutations are responsible for the
      occurrence of familial adenomatous polyposis (FAP). Somatic mutations lead to
      malignant transformation of adenomas. In this context, considering the
      significance of APC germline mutations in FAP, we aimed to identify APC germline
      mutations. In the present study, 20 FAP patients were enrolled. The determination
      of APC germline mutations was performed using sequencing, and the mutations were
      compared with clinical markers (gender, age at diagnosis, smoking habits, TNM
      stage, Astler-Coller stage, degree of differentiation of adenocarcinoma). The
      data were compared using the SPSS program, with the Fisher's exact test and chi2
      test, considering alpha=0.05. According to the main results in our sample, 16
      alleles with deleterious mutations (80% of the patients) were identified while 7
      (35%) patients had no deleterious mutations. There was a predominance of nonsense
      (45% of the patients) and frameshift (20% of the patients) mutations. There was
      no statistical significance between the APC germline mutations identified and the
      clinical variables considered in our study. Only TNM stage was associated with
      the presence of deleterious mutations. Patients with deleterious mutations had an
      OR, 0.086 (IC=0.001-0.984); TNM stage I+II in comparison with III+IV, when
      compared with the patients with no deleterious mutations identified. In this
      context, as a conclusion, we demonstrated the molecular heterogeneity of APC
      germline mutations in FAP and the difficulty to perform molecular diagnostics in
      a Brazilian population, considering the admixed population analyzed.

PMID- 23970362
TI  - HIF-1alpha inhibition sensitizes pituitary adenoma cells to temozolomide by
      regulating MGMT expression.
AB  - Suppression of hypoxia-inducible factor 1alpha (HIF-1alpha) has been shown to
      sensitize glioblastoma cells to temozolomide (TMZ) treatment via down-modulation
      of O6-methylguanine-DNA methyltransferase (MGMT) expression. To date, whether the
      efficacy of TMZ therapy is correlated with MGMT expression and whether HIF-1alpha
      suppression exerts similar effects in human pituitary adenoma cells have not been
      defined. In the present study, using an HIF-1alpha knockdown strategy and the HIF
      1alpha inhibitor 2-methoxyestradiol (2ME), we demonstrated for the first time
      that HIF-1alpha suppression increases the efficacy of TMZ in human pituitary
      adenoma cells in vitro and in vivo. Our mechanistic study showed that HIF-1alpha
      suppression resulted in down-modulation of MGMT expression and decreased DNA
      damage repair ability as demonstrated by decreased RAD51 protein expression.
      These results suggest an HIF-1alpha-dependent regulation of MGMT expression in
      human pituitary adenoma cells, and HIF-1alpha knockdown or the HIF-1alpha
      inhibitor 2ME can confer TMZ sensitization in human pituitary adenomas. The
      clinical application of 2ME as an adjuvant therapy may be a potential approach to
      improve the efficacy of TMZ therapy for pituitary adenomas. 

PMID- 23970363
TI  - Differential effects of nonselective versus selective beta-blockers on cardiac
      sympathetic activity and hemostasis in patients with heart failure.
AB  - Carvedilol, a nonselective beta-blocker, may be more effective than the selective
      beta-blocker metoprolol in reducing the risk of thromboembolic events in heart
      failure. The aim of this study was, first, to assess whether there is a
      differential response in cardiac sympathetic activity by (123)I-meta
      iodobenzylguanidine ((123)I-MIBG) imaging when either beta-blocker is used.
      Second, we assessed whether that response correlates with levels of various serum
      factors that serve as markers for coagulability. METHODS: In this prospective,
      randomized, open-label crossover study with masked outcome assessments, stable
      heart failure patients (left ventricular ejection fraction < 40%) homozygous for
      the Arg16/Gln27 (n = 13) or Gly16/Glu27 haplotype (n = 8) of the beta2-receptor
      were randomized to equipotent dosages of carvedilol or metoprolol for two 6-wk
      periods. Primary outcome was sympathetic activity as measured by (123)I-MIBG
      myocardial washout. Secondary outcomes included markers of hemostasis. RESULTS:
      (123)I-MIBG cardiac washout was lower during carvedilol than metoprolol treatment
      (12.9% +/- 3.9% vs. 22.1% +/- 2.8%, respectively, P = 0.003), irrespective of
      beta2-adrenergic receptor haplotype. In addition, treatment with carvedilol
      resulted in a lower von Willebrand factor than did metoprolol (149% +/- 13% vs.
      157% +/- 13%, respectively, P = 0.01), irrespective of beta2-adrenergic receptor
      haplotype. CONCLUSION: Compared with metoprolol, carvedilol resulted in greater
      reduction of sympathetic activity after 6 wk of treatment and lower von
      Willebrand factor concentrations in both Arg16/Gln27 and Gly16/Glu27 individuals.
      Therefore, carvedilol may reduce the risk of thromboembolic events in patients
      with heart failure, irrespective of beta2-receptor haplotype status.

PMID- 23970364
TI  - Feasibility and predictability of perioperative PET and estrogen receptor ligand
      in patients with invasive breast cancer.
AB  - The presence of estrogen receptor (ER) in breast cancer is a prognostic indicator
      for both disease-free and overall survival. 16alpha-(18)F-fluoro-17beta-estradiol
      ((18)F-FES) with PET is a noninvasive test for evaluation of ER expression and
      has been used for predicting response to endocrine therapy in patients with ER
      positive metastatic breast cancer. The purpose of this study was to correlate
      (18)F-FES PET and ER expression in patients with primary, operable breast cancer.
      METHODS: Forty-eight patients were prospectively enrolled in an institutional
      review board-approved protocol and signed an informed consent form. All patients
      had undergone (18)F-FES PET preoperatively. Clinical characteristics, tumor
      characteristics, and treatment outcomes were recorded. Immunohistochemical
      analysis for ER and progesterone receptor (PgR) percentage expression (46
      surgical, 2 core biopsy specimens) was performed. (18)F-FES PET standardized
      uptake value (SUV) of the breast lesion was correlated with percentage
      immunohistochemistry ER and PgR expression. (18)F-FES PET SUV was quantified,
      with a value of 1.5 or more considered positive, and ER and PgR was quantified,
      with 1% or more considered positive. Formalin-fixed paraffin-embedded tissue was
      available for 44 patients (42 surgical, 2 core biopsy specimens). We used a
      microarray platform, and estrogen-related gene expression data (ESR1, ESR2, and
      PGR) were compared with (18)F-FES PET SUV (Spearman rank correlation). Tumor
      size, ductal histology, grade, HER2-neu overexpression, PgR expression, estradiol
      level, body mass index (BMI), and lean BMI were compared with (18)F-FES PET
      uptake using univariate and multivariate analysis. RESULTS: Forty-eight patients
      completed our protocol, and 2 patients did not undergo surgery because bone
      metastases were identified preoperatively on (18)F-FES PET. Eighty-three percent
      of our patients were stage I or II, with a median tumor size of 1.9 cm. Forty-one
      patients underwent a sentinel node biopsy. Twenty-one patients had nodal
      involvement. (18)F-FES PET identified 5 patients with axillary nodal uptake
      (median SUV, 3.0; range, 1.7-6.9). These 5 patients had ER-positive breast
      cancer, and all had more than 4 positive nodes at the time of axillary node
      dissection. (18)F-FES PET SUV was associated with immunohistochemistry ER
      expression. The sensitivity and specificity of the (18)F-FES PET for the breast
      lesion were 0.85 and 0.75, respectively. Estrogen and progesterone gene
      expression (ESR1, ESR2, and PGR) was not associated with (18)F-FES PET SUV
      (Spearman rank correlation). We found a significant correlation between (18)F-FES
      PET SUV and tumor size (P = 0.0015) but not with ductal histology, grade, HER2
      neu overexpression, PgR, estradiol, BMI, or lean BMI (logistic regression). ER
      expression (P < 0.001) and tumor size (P < 0.0001) were significant on
      multivariate regression analysis. CONCLUSION: (18)F-FES PET SUV correlated with
      ER immunohistochemistry expression but not gene expression in our patients with
      early breast cancer. We found that size of primary tumor was significantly
      associated with (18)F-FES PET SUV. (18)F-FES PET is highly predictive for
      metastatic disease and helped in the identification of patients with metastatic
      disease in a preoperative setting.

PMID- 23970365
TI  - 18F-FDG PET and combined 18F-FDG-contrast CT parameters as predictors of tumor
      control for hepatocellular carcinoma after stereotactic ablative radiotherapy.
AB  - The application of stereotactic ablative radiotherapy (SABR) to hepatocellular
      carcinoma (HCC) is emerging. To identify pretreatment prognostic indicators is
      crucial for patient selection and optimal individual therapy. The aim of this
      study was to determine whether (18)F-FDG PET and a combined (18)F-FDG-contrast CT
      parameter could be useful tools to predict tumor control for patients with HCC
      treated by SABR. METHODS: We retrospectively identified 31 patients (41 tumors)
      who underwent (18)F-FDG PET before SABR between November 2007 and September 2011.
      (18)F-FDG PET parameters were collected as prognostic indicators, including
      visual PET scale (+/-), maximal standardized uptake value (SUV) of the tumor (T
      SUV max), ratio of T SUV max to maximal normal-liver SUV, ratio of T SUV max to
      mean normal-liver SUV, and score combining tumor volume and T SUV max (CT/(18)F
      FDG PET score). They underwent SABR with a median dose of 42 Gy (ranging from 30
      to 50 Gy) in 4-5 fractions. (18)F-FDG PET parameters and clinical factors were
      tested as predictors of tumor control and patient survival. RESULTS: The median
      follow-up time was 18 mo. Among the parameters examined, T SUV max and CT/(18)F
      FDG PET score were significantly correlated with tumor control. T SUV max with a
      cutoff value of 3.2 was the most significant prognostic indicator. The 4-y
      control rate was 86.2% in tumors with a T SUV max of 3.2 or less but only 37.5%
      in those with a T SUV max of more than 3.2 (adjusted hazard ratio, 9.40; 95%
      confidence interval, 1.18-74.76; P = 0.034). CT/(18)F-FDG PET score (<= 4 vs. >4)
      was also a significant predictor of tumor control after SABR. Tumors with a
      CT/(18)F-FDG PET score of more than 4 had a 5.23-fold risk of tumor failure.
      After adjustment for factors of sex, American Joint Committee on Cancer stage,
      Cancer of the Liver Italian Program score, and Child-Pugh classification, tumors
      with a score of more than 4 had a 4.96-fold risk of failure after SABR, compared
      with tumors with a score of 4 or less. For overall survival, none was
      statistically significant. CONCLUSION: The use of (18)F FDG PET to predict tumor
      control is feasible. T SUV max with a cutoff value of 3.2 is the best prognostic
      indicator. We suggest that (18)F-FDG PET may be a reference for prognostic
      prediction, patient selection, and radiation dose adjustment for HCC patients
      treated with SABR.

PMID- 23970367
TI  - In vivo PET/CT in a human glioblastoma chicken chorioallantoic membrane model: a
      new tool for oncology and radiotracer development.
AB  - For many years the laboratory mouse has been used as the standard model for in
      vivo oncology research, particularly in the development of novel PET tracers, but
      the growth of tumors on chicken chorioallantoic membrane (CAM) provides a more
      rapid, low cost, and ethically sustainable alternative. For the first time, to
      our knowledge, we demonstrate the feasibility of in vivo PET and CT imaging in a
      U87 glioblastoma tumor model on chicken CAM, with the aim of applying this model
      for screening of novel PET tracers. METHODS: U87 glioblastoma cells were
      implanted on the CAM at day 11 after fertilization and imaged at day 18. A small
      animal imaging cell was used to maintain incubation and allow anesthesia using
      isoflurane. Radiotracers were injected directly into the exposed CAM vasculature.
      Sodium (18)F-fluoride was used to validate the imaging protocol, demonstrating
      that image-degrading motion can be removed with anesthesia. Tumor glucose
      metabolism was imaged using (18)F-FDG, and tumor protein synthesis was imaged
      using 2-(18)F-fluoro-l-tyrosine. Anatomic images were obtained by contrast
      enhanced CT, facilitating clear delineation of the tumor, delineation of tracer
      uptake in tumor versus embryo, and accurate volume measurements. RESULTS: PET
      imaging of tumor glucose metabolism and protein synthesis was successfully
      demonstrated in the CAM U87 glioblastoma model. Catheterization of CAM blood
      vessels facilitated dynamic imaging of glucose metabolism with (18)F-FDG and
      demonstrated the ability to study PET tracer uptake over time in individual
      tumors, and CT imaging improved the accuracy of tumor volume measurements.
      CONCLUSION: We describe the novel application of PET/CT in the CAM tumor model,
      with optimization of typical imaging protocols. PET imaging in this valuable
      tumor model could prove particularly useful for rapid, high-throughput screening
      of novel radiotracers.

PMID- 23970368
TI  - The role of radionuclide imaging in epilepsy, Part 1: Sporadic temporal and
      extratemporal lobe epilepsy.
AB  - Epilepsy is one of the most common yet diverse neurologic disorders, affecting
      almost 1%-2% of the population. Presently, radionuclide imaging such as PET and
      SPECT is not used in the primary diagnosis or evaluation of recent-onset
      epilepsy. However, it can play a unique and important role in certain specific
      situations, such as in noninvasive presurgical localization of epileptogenic
      brain regions in intractable-seizure patients being considered for epilepsy
      surgery. Radionuclide imaging can be particularly useful if MR imaging is either
      negative for lesions or shows several lesions of which only 1 or 2 are suspected
      to be epileptogenic and if electroencephalogram changes are equivocal or
      discordant with the structural imaging. Similarly, PET and SPECT can also be
      useful for evaluating the functional integrity of the rest of the brain and may
      provide useful information on the possible pathogenesis of the neurocognitive and
      behavioral abnormalities frequently observed in these patients. 

PMID- 23970369
TI  - Kinetic modeling, test-retest, and dosimetry of 123I-MNI-420 in humans.
AB  - In vivo imaging of adenosine 2A receptors (A2A) in the brain has attracted
      significant interest from the scientific community, because studies have shown
      that dysregulation of these receptors is implicated in a variety of
      neurodegenerative and psychiatric disorders, including Parkinson and Huntington
      diseases. This work aimed to describe the kinetic properties, test-retest
      results, and dosimetry estimates of (123)I-MNI-420, a SPECT radiotracer for the
      in vivo imaging of A2A in the brain. METHODS: Nine healthy human subjects were
      enrolled in this study; 7 completed (123)I-MNI-420 brain SPECT studies, and 2
      participated in whole-body planar imaging evaluating (123)I-MNI-420
      biodistribution and dosimetry. For 3 of the brain SPECT studies, arterial blood
      was collected for invasive modeling. Noninvasive models were also explored,
      including Logan graphical analysis and simplified reference tissue models. Test
      retest reliability was assessed in 4 subjects. To evaluate radiotracer
      biodistribution and dosimetry, serial whole-body images were acquired immediately
      after injection and at selected time points after injection. Urine samples were
      collected over a period of 21 h to calculate urinary excretion. RESULTS: (123)I
      MNI-420 rapidly entered the human brain and displayed uptake consistent with
      known A2A densities. At pseudoequilibrium (reached at 90 min after radiotracer
      injection), stable target-to-cerebellum ratios of around 1.4-2.0 were determined.
      Binding potentials around 0.8-1.2 were estimated using different kinetic models
      and the cerebellum as the reference region. Average test-retest variability in
      the striatum was 4.8%, 3.5%, and 6.5% for the simplified reference tissue model,
      Logan graphical analysis, and standardized uptake value ratio methods,
      respectively. The estimated radiation effective dose determined from whole-body
      studies was 0.036 mSv/MBq. CONCLUSION: The data indicate that (123)I-MNI-420 is a
      useful SPECT radiotracer for imaging A2A in the brain and has radiation doses
      that would allow for multiple scans in the same research subject each year. The
      availability of (123)I-MNI-420 offers the possibility of investigating A2A
      activity in specific conditions and evaluating drug occupancy for A2A candidate
      therapeutics.

PMID- 23970370
TI  - Controlled synthesis of Mn3O4 nanoparticles in ionic liquids.
AB  - This work describes a simple one-step synthesis of Mn3O4 nanoparticles by thermal
      decomposition of [Mn(acac)2] (acac = acetylacetonate) using imidazolium ionic
      liquids (ILs) and a conventional solvent, oleylamine, for comparison. The Mn3O4
      nanoparticles were characterized by XRD, ATR-FTIR, TEM, Raman, UV/VIS and
      magnetometry techniques. The addition of 1-n-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)amide IL (BMI.NTf2) yielded a smaller particle size
      (9.9 +/- 1.8 nm) with better dispersion and more regular sizes than synthesis
      using oleylamine as the solvent (12.1 +/- 3.0 nm). The complete conversion of the
      precursor to Mn3O4 nanoparticles occurred after 96 h at 180  degrees C for the
      reaction performed in BMI.NTf2. However, under these reaction conditions in
      oleylamine, no precursor was detected, but two different phases were observed: a
      major phase corresponding to Mn3O4 and a minor phase corresponding to MnO2.
      Magnetometry revealed that Mn3O4 nanoparticles synthesized in either oleylamine
      or BMI.NTf2 exhibited ferrimagnetic behavior at low temperatures, whereas they
      were paramagnetic at room temperature. As expected, the blocking temperature and
      the coercivity decreased with the size of nanoparticles. Our results demonstrate
      that reaction conditions such as time, and the nature of the ionic liquid play
      important roles in determining the size of Mn3O4 nanoparticles. 

PMID- 23970371
TI  - Clinical applications of capillary electrophoresis coupled to mass spectrometry
      in biomarker discovery: Focus on Bladder Cancer.
AB  - A major requirement in the application of proteins as clinical biomarkers is that
      they provide a highly sensitive and specific result in disease assessment. Since
      single biomarkers are generally of limited accuracy, a group or panel of well
      characterized biomarkers appears appropriate, providing a more robust and
      sensitive mass-spectrometry-based analytical platform. Capillary electrophoresis
      coupled to MS has been successfully used in biomarker discovery and application,
      as it enables the selective detection of peptides and small proteins, combining
      the high separation capacity of CE with the advanced sensitivity of MS. CE-MS
      allows the characterization of highly complex samples (such as urine, plasma and
      other biofluids) in a consistent and reproducible way. It has a range of
      applications, many focusing especially in studies on urinary peptide biomarkers
      in kidney and cardiovascular diseases. Another major field of interest has been
      malignancy of the genitourinary system. In the first part of this review we cover
      technical aspects and performance characteristics of CE-MS, with special focus on
      the requirements for biomarker discovery and clinical application. In the second
      part, we review the potential and development of CE-MS in the management of
      genitourinary cancers, especially bladder cancer (BCa). CE-MS has been employed
      in several studies aimed at discovering biomarkers for BCa that may be useful in
      diagnosis, monitoring for recurrence, and prediction of the risk for the muscle
      invasive stage. In the last part of the review we discuss current challenges and
      provide an outlook for ongoing and possible future developments. 

PMID- 23970372
TI  - Supervised exercise therapy versus non-supervised exercise therapy for
      intermittent claudication.
AB  - BACKGROUND: Although supervised exercise therapy is considered to be of
      significant benefit for people with leg pain (peripheral arterial disease (PAD)),
      implementing supervised exercise programs (SETs) in daily practice has
      limitations. This is an update of a review first published in 2006. OBJECTIVES:
      The main objective of this review was to provide an accurate overview of studies
      evaluating the effects of supervised versus non-supervised exercise therapy on
      maximal walking time or distance on a treadmill for people with intermittent
      claudication. SEARCH METHODS: For this update, the Cochrane Peripheral Vascular
      Diseases Group Trials Search Co-ordinator searched the Specialised Register (last
      searched September 2012) and CENTRAL (2012, Issue 9). In addition, we
      handsearched the reference lists of relevant articles for additional trials. No
      restriction was applied to language of publication. SELECTION CRITERIA:
      Randomized clinical trials comparing supervised exercise programs with non
      supervised exercise programs (defined as walking advice or a structural home
      based exercise program) for people with intermittent claudication. Studies with
      control groups, which did not receive exercise or walking advice or received
      usual care (maintained normal physical activity), were excluded. DATA COLLECTION
      AND ANALYSIS: Two review authors (HJPF and BLWB) independently selected trials
      and extracted data. Three review authors (HJPF, BLWB, and GJL) assessed trial
      quality, and this was confirmed by two other review authors (MHP and JAWT). For
      all continuous outcomes, we extracted the number of participants, the mean
      differences, and the standard deviation. The 36-Item Short Form Health Survey (SF
      36) outcomes were extracted to assess quality of life. Effect sizes were
      calculated as the difference in treatment normalized with the standard deviation
      (standardized mean difference) using a fixed-effect model. MAIN RESULTS: A total
      of 14 studies involving a total of 1002 male and female participants with PAD
      were included in this review. Follow-up ranged from six weeks to 12 months. In
      general, supervised exercise regimens consisted of three exercise sessions per
      week. All trials used a treadmill walking test as one of the outcome measures.
      The overall quality of the included trials was moderate to good, although some
      trials were small with respect to the number of participants, ranging from 20 to
      304.Supervised exercise therapy (SET) showed statistically significant
      improvement in maximal treadmill walking distance compared with non-supervised
      exercise therapy regimens, with an overall effect size of 0.69 (95% confidence
      interval (CI) 0.51 to 0.86) and 0.48 (95% CI 0.32 to 0.64) at three and six
      months, respectively. This translates to an increase in walking distance of
      approximately 180 meters that favored the supervised group. SET was still
      beneficial for maximal and pain-free walking distances at 12 months, but it did
      not have a significant effect on quality of life parameters. AUTHORS'
      CONCLUSIONS: SET has statistically significant benefit on treadmill walking
      distance (maximal and pain-free) compared with non-supervised regimens. However,
      the clinical relevance of this has not been demonstrated definitively; additional
      studies are required that focus on quality of life or other disease-specific
      functional outcomes, such as walking behavior, patient satisfaction, costs, and
      long-term follow-up. Professionals in the vascular field should make SET
      available for all patients with intermittent claudication.

PMID- 23970373
TI  - Effect of anti-osteoporotic agents on the prevention of bone loss in unloaded
      bone.
AB  - Pharmaceutical countermeasures to treat disuse osteoporosis are rarely studied.
      Pharmaceutical studies for the treatment and prevention of osteoporosis depend on
      the ovariectomized rat model, which is a suitable model for the disease in women.
      Disuse osteoporosis affects men and women, but there is lack of awareness and
      relevant pharmaceutical studies for this condition. The objectives of this study
      were to verify the validity of an unusual tail-suspension rat model in the
      induction of disuse osteoporosis and subsequent pharmaceutical treatments. This
      model was created by unloading the hind limbs of the rats in order to create a
      state of weightlessness in their hindlimb bones. Validation of the model was
      performed with non-suspended rats. This study included five groups of suspended
      rats fed with different agents, such as distilled water (control), high-, medium-
      and low-dose raloxifene and a bisphosphonate (alendronate). The experiment lasted
      for 28 days. Comparisons were made between the suspended control and treatment
      groups. Ovariectomized and sham-operated rats were also included as a reference
      for bone changes during osteoporosis. Changes in bone mineral density (BMD) at
      the distal femur and proximal tibia, microarchitecture at the distal femur and
      biomechanical strength at the diaphyseal femur were studied. Reduction of BMD and
      deterioration of trabeculae were similar between the suspended control and
      ovariectomized rats. Loss of BMD induced by tail suspension was reduced most
      effectively by medium-dose raloxifene. Deterioration of trabecular
      microarchitecture was also prevented by raloxifene. The tail-suspension rat model
      is suitable for the study of disuse osteoporosis under the effects of various
      therapeutic agents. The preventive effects of raloxifene against bone loss under
      disuse conditions have been demonstrated using this model.

PMID- 23970374
TI  - Overexpression of miR-708 and its targets in the childhood common precursor B
      cell ALL.
AB  - BACKGROUND: The critical function of microRNAs in the pathogenesis and prognosis
      of hematopoietic cancer has become increasingly apparent. However, only a few
      miRNAs have been reported to be altered in acute lymphocytic leukemia (ALL).
      PROCEDURES: To uncover aberrantly expressed miRNAs in pediatric B-cell ALL, our
      study employed genome-wide miRNA microarray analysis and stem-loop real-time
      quantitative polymerase chain reaction (qRT-PCR) to examine common precursor B
      cell ALL samples. The target genes of miRNA-708 were then identified and verified
      by bioinformatics, dual-luciferase reporter assay, qRT-PCR, and Western blot.
      RESULTS: Significant upregulation of miR-708, miR-210, and miR-181b, and
      downregulation of miR-345 and miR-27a were observed in common precursor B-cell
      ALL (common-ALL) samples (P < 0.05). In addition, elevated expression of miR-708
      and miR-181b were found in high-risk common-ALL compared to standard and
      intermediate ones. miR-708 inhibited luciferase reporter activity by binding to
      the 3'-untranslated regions (3'-UTRs) of CNTFR, NNAT, and GNG12 mRNA in HEK-293
      cell line and suppressed the protein levels of CNTFR, NNAT, and GNG12 in Jurkat
      cells. In addition, mRNA levels of CNTFR and NNAT, but not of GNG12, were found
      to be downregulated in high risk common-ALL samples. Mutational analysis revealed
      that miR-708 binds to the 394-400 bp sequence region of the 3'-UTR of CNTFR mRNA.
      CONCLUSION: The expression level of miR-708 reflects differences among the
      clinical types of common-ALL, and CNTFR, NNAT, and GNG12 were identified as
      targets of miR-708.

PMID- 23970375
TI  - Platelet a disintegrin and metallopeptidase 10 expression correlates with clock
      drawing test scores in Alzheimer's disease.
AB  - OBJECTIVE: Earlier studies have demonstrated that a disintegrin and
      metallopeptidase 10 (ADAM10) levels are reduced in Alzheimer's disease (AD)
      patients compared with healthy subjects. The objective of this study was to
      evaluate whether platelet ADAM10 levels correlates with the clock drawing test
      (CDT) scores, which is a simple and a reliable measure of visuospatial ability
      and executive function in AD patients. METHODS: Thirty elderly patients with
      probable AD and 25 healthy patients forming the control group, matched by age,
      gender, and educational level, were evaluated. Platelet proteins were analyzed by
      sodium dodecyl sulfate polyacrylamide gel electrophoresis, and ADAM10 was
      identified by western blotting. The Spearman's correlation coefficient between
      ADAM10 and CDT was obtained for each group. The areas under the curves were used
      to compare the receiver operating characteristic curves. RESULTS: The CDT scores
      and platelet ADAM10 expression were significantly different between patients with
      AD and controls and also along the disease's progression. In AD patients, there
      was a positive correlation between ADAM10 expression and CDT scores. Among non-AD
      subjects, no correlation was found. The combination of ADAM10 and CDT was
      significantly better to confirm the AD diagnosis than the AUCs of ADAM10 and CDT
      separately. CONCLUSIONS: The association of blood-based biomarkers, such as
      ADAM10, and cognitive tests may be helpful for a more reliable AD diagnosis.

PMID- 23970376
TI  - Role of the Hedgehog pathway in hepatocellular carcinoma (review).
AB  - The Hedgehog (Hh) pathway is an evolutionarily conserved signaling mechanism that
      controls many aspects of cell differentiation and the development of tissues and
      organs during embryogenesis. Early investigations have focused on the effects of
      Hh activity on the development of organs including skin, gut, the nervous system
      and bone. However, in addition to normal developmental processes, these
      investigations also found that Hh signaling is involved in aberrant proliferation
      and malignant transformation. Consequently, the role of Hh in cancer pathology,
      and its modulation by environmental factors is the subject of many
      investigations. Numerous environmental toxins, alcohol, and hepatitis viruses can
      cause hepatocellular carcinoma (HCC), which is the most common form of liver
      cancer. Significant hyperactivation of Hh signaling has been observed in liver
      injury and cirrhosis which often leads to the development of HCC lesions.
      Moreover, Hh activity plays an important role in the progression of HCC. Here, we
      review findings relevant to our understanding of the role of Hh signaling in HCC
      pathogenesis. 

PMID- 23970378
TI  - Quantification of seven apolipoproteins in human plasma by proteotypic peptides
      using fast LC-MS/MS.
AB  - PURPOSE: We investigated different sample pretreatment strategies and developed a
      standardized sample pretreatment protocol for absolute quantification of seven
      apolipoproteins (Apos) in human serum by LC-MS/MS using proteotypic peptides and
      corresponding stable isotope-labeled peptides as internal standards. EXPERIMENTAL
      DESIGN: Micro-LC was coupled with quadrupole-linear ion trap MS for
      quantification and peptide confirmation. Denaturation, reduction, alkylation, and
      tryptic digestion including ultrasound and microwave assistance were
      investigated. Method comparison of 50 plasma samples with an immunoassay was
      performed for Apo A-I and Apo B. RESULTS: Tryptic digestion times ranged between
      5 min (Apo A-I, Apo E, Apo A-IV) and 16 h (Apo A-II). Ultrasound and microwave
      assistance did not improve the digestion yield. Linearity was found between 0.1
      nmol/L and 100 mmol/L. The lower limits of quantification were <= 0.4 MUmol/L for
      Apo A-I, Apo A-IV, Apo B-100, Apo C-I, Apo C-III, Apo E, and <1.4 MUmol/L for Apo
      A-II. CV <13% were determined. Comparison with immunoassays showed a good
      agreement for Apo A-I and Apo B. CONCLUSION AND CLINICAL RELEVANCE: The validated
      preanalytical protocol enables a reliable simultaneous analysis of seven Apos in
      human serum without depletion. The method can now be applied in clinical studies
      to investigate the Apo distributions in cardiovascular diseases.

PMID- 23970379
TI  - Targeting autophagy potentiates the apoptotic effect of histone deacetylase
      inhibitors in t(8;21) AML cells.
AB  - The role of autophagy during leukemia treatment is unclear. On the one hand,
      autophagy might be induced as a prosurvival response to therapy, thereby reducing
      treatment efficiency. On the other hand, autophagy may contribute to degradation
      of fusion oncoproteins, as recently demonstrated for promyelocytic leukemia
      retinoic acid receptor alpha and breakpoint cluster region-abelson, thereby
      facilitating leukemia treatment. Here, we investigated these opposing roles of
      autophagy in t(8;21) acute myeloid leukemia (AML) cells, which express the most
      frequently occurring AML fusion oncoprotein, AML1-eight-twenty-one (ETO). We
      demonstrate that autophagy is induced by AML1-ETO-targeting drugs, such as the
      histone deacetylase inhibitors (HDACis) valproic acid (VPA) and vorinostat.
      Furthermore, we show that autophagy does not mediate degradation of AML1-ETO but
      rather has a prosurvival role in AML cells, as inhibition of autophagy
      significantly reduced the viability and colony-forming ability of HDACi-treated
      AML cells. Combined treatment with HDACis and autophagy inhibitors such as
      chloroquine (CQ) led to a massive accumulation of ubiquitinated proteins that
      correlated with increased cell death. Finally, we show that VPA induced autophagy
      in t(8;21) AML patient cells, and combined treatment with CQ enhanced cell death.
      Because VPA and CQ are well-tolerated drugs, combinatorial therapy with VPA and
      CQ could represent an attractive treatment option for AML1-ETO-positive leukemia.

PMID- 23970382
TI  - microRNA-18b is upregulated in breast cancer and modulates genes involved in cell
      migration.
AB  - microRNAs are small non-coding RNAs of ~22 nucleotides that function at post
      transcriptional level as negative regulators of gene expression. Aberrant
      expression of microRNAs could promote uncontrolled proliferation, migration and
      invasion of human cancer cells. In this study, we analyzed the expression of
      microRNA-18b (miR-18b) in breast cancer cell lines and in a set of clinical
      specimens. Our results showed that miR-18b was upregulated in four out of five
      breast cancer cell lines and also in breast tumors. In order to identify
      potential gene targets, we carried out transcriptional profiling of MDA-MB-231
      breast cancer cells that ectopically expressed miR-18b. Our results showed that
      263 genes were significantly modulated in miR-18b-deficient cells (fold change
      >1.5; P<=0.05). We found that knock-down of miR-18b induced the upregulation of
      55 olfactory receptor (OR) genes and nine genes (NLRP7, KLK3, OLFM3, POSTN,
      MAGED4B, KIR3DL3, CRX, SEMG1 and CEACAM5) with key roles in cell migration and
      metastasis. Consistently, we found that ectopic inhibition of miR-18b suppressed
      the migration of two breast cancer cell models in vitro. In conclusion, we have
      uncovered genes directly or indirectly modulated by miR-18b which may represent
      potential therapeutic targets in breast cancer. Our data also pointed out a role
      of miR-18b in migration of breast cancer cells. 

PMID- 23970381
TI  - Association of hospital construction with the development of healthcare
      associated environmental mold infections (HAEMI) in pediatric patients with
      leukemia.
AB  - BACKGROUND: Healthcare associated mold infections (HAEMI) increase morbidity and
      mortality in children with leukemia. Excavation adjacent to Children's Medical
      Center Dallas (CMCD) April 2006-February 2007 provided an opportunity to
      determine if excavation adjacent to a hospital building is associated with
      increased risk of developing HAEMI in children receiving intensive chemotherapy
      for acute leukemia. METHODS: Children who began receiving intensive chemotherapy
      for acute leukemia at CMCD from 2004 to 2008 were identified (n = 275). Exposures
      to the CMCD campus during intensive chemotherapy and duration of neutropenia per
      exposure were recorded. Proven, probable, or possible invasive fungal disease
      (IFD) was classified using EORTC/MSG guidelines. Institutional guidelines
      categorized mold infections as definite or possible HAEMI. A bivariate time-to
      event model compared the association of excavation with HAEMI and yeast
      infections, controlling for neutropenia. RESULTS: There were 7,454 CMCD
      exposures, 1,007 (13.5%) during excavation. Of 50 cases of IFD, 31 were HAEMI. By
      time-to-event analysis exposure to the CMCD campus during the excavation period
      was significantly associated with HAEMI (HR = 2.8, P = 0.01) but not yeast
      infections (HR = 0.75, P = 0.75). Neutropenia was significantly associated with
      both HAEMI and yeast infections (P < 0.001). Voriconazole prophylaxis did not
      prevent HAEMI in 42% of the 14 patients with AML who had been receiving this
      agent. CONCLUSION: This study is the first to demonstrate an association between
      exposure to hospital construction that includes excavation and HAEMI in pediatric
      oncology patients. Since neutropenic patients need protection from aerosolized
      fungal spores during visits to expanding medical centers, preventive strategies
      with adherence monitoring need additional study.

PMID- 23970380
TI  - Preclinical and clinical efficacy of XPO1/CRM1 inhibition by the karyopherin
      inhibitor KPT-330 in Ph+ leukemias.
AB  - As tyrosine kinase inhibitors (TKIs) fail to induce long-term response in blast
      crisis chronic myelogenous leukemia (CML-BC) and Philadelphia chromosome-positive
      (Ph(+)) acute lymphoblastic leukemia (ALL), novel therapies targeting leukemia
      dysregulated pathways are necessary. Exportin-1 (XPO1), also known as chromosome
      maintenance protein 1, regulates cell growth and differentiation by controlling
      the nucleocytoplasmic trafficking of proteins and RNAs, some of which are
      aberrantly modulated in BCR-ABL1(+) leukemias. Using CD34(+) progenitors from
      CML, B-ALL, and healthy individuals, we found that XPO1 expression was markedly
      increased, mostly in a TKI-sensitive manner, in CML-BC and Ph(+) B-ALL. Notably,
      XPO1 was also elevated in Ph(-) B-ALL. Moreover, the clinically relevant XPO1
      inhibitor KPT-330 strongly triggered apoptosis and impaired the clonogenic
      potential of leukemic, but not normal, CD34(+) progenitors, and increased
      survival of BCR-ABL1(+) mice, 50% of which remained alive and, mostly, became BCR
      ABL1 negative. Moreover, KPT-330 compassionate use in a patient with TKI
      resistant CML undergoing disease progression significantly reduced white blood
      cell count, blast cells, splenomegaly, lactate dehydrogenase levels, and bone
      pain. Mechanistically, KPT-330 altered the subcellular localization of leukemia
      regulated factors including RNA-binding heterogeneous nuclear ribonucleoprotein
      A1 and the oncogene SET, thereby inducing reactivation of protein phosphatase 2A
      tumor suppressor and inhibition of BCR-ABL1 in CML-BC cells. Because XPO1 is
      important for leukemic cell survival, KPT-330 may represent an alternative
      therapy for TKI-refractory Ph(+) leukemias. 

PMID- 23970383
TI  - Evaluating the roles of autophagy and lysosomal trafficking defects in
      intracellular distribution-based drug-drug interactions involving lysosomes.
AB  - Many currently approved drugs possess weakly basic properties that make them
      substrates for extensive sequestration in acidic intracellular compartments such
      as lysosomes through an ion trapping-type mechanism. Lysosomotropic drugs often
      have unique pharmacokinetic properties that stem from the extensive entrapment in
      lysosomes, including an extremely large volume of distribution and a long half
      life. Accordingly, pharmacokinetic drug-drug interactions can occur when one drug
      modifies lysosomal volume such that the degree of lysosomal sequestration of
      secondarily administered drugs is significantly altered. In this work, we have
      investigated potential mechanisms for drug-induced alterations in lysosomal
      volume that give rise to drug-drug interactions involving lysosomes. We show that
      eight hydrophobic amines, previously characterized as perpetrators in this type
      of drug-drug interaction, cause a significant expansion in lysosomal volume that
      was correlated with both the induction of autophagy and with decreases in the
      efficiency of lysosomal egress. We also show that well-known chemical inducers of
      autophagy caused an increase in apparent lysosomal volume and an increase in
      secondarily administered lysosomotropic drugs without negatively impacting
      vesicle-mediated lysosomal egress. These results could help rationalize how the
      induction of autophagy could cause variability in the pharmacokinetic properties
      of lysosomotropic drugs.

PMID- 23970384
TI  - Identification of inferior pancreaticoduodenal artery during
      pancreaticoduodenectomy using augmented reality-based navigation system.
AB  - BACKGROUND: In pancreaticoduodenectomy (PD), early ligation of the inferior
      pancreaticoduodenal artery (IPDA) before efferent veins has been advocated to
      decrease blood loss by congestion of the pancreatic head to be resected. In this
      study, we herein report the utility of early identification of the IPDA using an
      augmented reality (AR)-based navigation system (NS). METHODS: Seven
      nonconsecutive patients underwent PD using AR-based NS. After paired-point
      matching registration, the reconstructed image obtained by preoperative computed
      tomography (CT) was fused with a real-time operative field image and displayed on
      3D monitors. The vascular reconstructed images, including the superior mesenteric
      artery, jejunal artery, and IPDA were visualized to facilitate image-guided
      surgical procedures. We compared operating time and intraoperative blood loss of
      six patients who successfully underwent identification of IPDA using AR-based NS
      (group A) with nine patients who underwent early ligation of IPDA without using
      AR (group B) and 18 patients who underwent a conventional PD (group C). RESULTS:
      The IPDA or the jejunal artery was rapidly identified and ligated in six
      patients. The mean operating time and intraoperative blood loss in group A was
      415 min and 901 ml, respectively. There was no significant difference in
      operating time and intraoperative blood loss among the groups. CONCLUSIONS: The
      AR-based NS provided precise anatomical information, which allowed the surgeons
      to rapidly identify and perform early ligation of IPDA in PD.

PMID- 23970385
TI  - Head and neck presentations of B-NHL and B-AL in children/adolescents: experience
      of the LMB89 study.
AB  - PURPOSE: Describe the epidemiology, clinical profiles and outcomes associated
      with head and neck (H&N) involvement in children/adolescents with B-cell non
      Hodgkin lymphoma (B-NHL). METHODS: Analysis of children/adolescents with H&N B
      NHL prospectively enrolled in the SFOP LMB-89 trial (July 1989-June 1996).
      RESULTS: One hundred and twelve of 561 patients (20%) had H&N involvement. The
      mean age of the patients was 8.4 years. Murphy staging differed between the H&N
      patients and the others (P < 0.0001): 9% versus 5% of the patients presented with
      stage I disease, 36% versus 11% presented with stage II disease, 12% versus 59%
      presented with stage III disease, 17% versus 10% with stage IV disease and 27%
      versus 16% with B-AL. Twenty-nine H&N patients (26%) had CNS involvement at
      diagnosis versus 8.5% in the group without H&N involvement (P < 0.0001). Patients
      were treated according to the LMB89 protocol: 3 H&N patients were allocated to
      group A, 70 to group B and 39 to group C. Ninety-seven percent of H&N patients
      achieved CR and event-free and overall survival at 4 years was 95.5% (5 deaths in
      patients with CNS disease). On multivariate analysis, EFS was significantly
      better in H&N patients than in non-H&N patients (P = 0.021), but not OS (P =
      0.11). CONCLUSION: The H&N site is the second most common location for B-NHL at
      diagnosis and is more frequently associated with disseminated disease and CNS
      involvement than other sites. However, outcomes are no worse for these patients
      than for the rest of the population.

PMID- 23970386
TI  - Formulation design and optimization for the improvement of nystatin-loaded lipid
      intravenous emulsion.
AB  - Nystatin (NYS) is a polyene macrolide with broad antifungal spectrum restricted
      to topical use owing to its toxicity upon systemic administration. The aims of
      this work were the design, development, and optimization of NYS-loaded lipid
      emulsion for intravenous administration. A closed circuit system was designed to
      apply ultrasound during the elaboration of the lipid intravenous emulsions
      (LIEs). Additionally, a comparison with the commercially available
      Intralipid((r)) 20% was also performed. Manufacturing conditions were optimized
      by factorial design. Formulations were evaluated in terms of physicochemical
      parameters, stability, release profile, and antimicrobial activity. The average
      droplet size, polydispersity index, zeta-potential, pH, and volume distribution
      values ranged between 192.5 and 143.0 nm, 0.170 and 0.135, -46 and -44 mV, 7.11
      and 7.53, 580 and 670 nm, respectively. The selected NYS-loaded LIE (NYS-LIE54)
      consisted of soybean oil (30%), soybean lecithin (2%), solutol HS((r)) 15 (4%),
      and glycerol (2.25%) was stable for at least 60 days. In vitro drug release
      studies of this formulation suggested a sustained-release profile. Equally, NYS
      LIE54 showed the best antimicrobial activity being higher than the free drug.
      Thus, it could be a promising drug delivery system to treat systemic fungal
      infections.

PMID- 23970387
TI  - [A Community-Based Concept for the Promotion of Health and Physical Activity in
      Children at Early School Age].
AB  - We promoted children's physical activity through a municipal and behaviour
      modifying approach in districts with deprived backgrounds. Using regular lessons,
      movement activities were performed with 316 pupils in their district once a month
      for 2 years. Meetings of involved parents, teachers and municipal representatives
      were held every 2 months to improve playgrounds and areas suitable for children's
      leisure activities. Questionnaires showed children's well-being to be correlated
      with physical outdoor activity, social contact with friends, regular dinners on
      school days and lower TV consumption. 

PMID- 23970388
TI  - [Sustainable Strategies for Health Promotion in Urban Districts].
AB  - In a city district striving to sustainably develop into a healthy living
      environment for its residents, cooperation with locally active players as well as
      network management and the inclusion of citizens and local businesses as non
      professional multipliers are particularly promising strategies for developing
      effective ways of promoting health and integrating them into existing structures
      in order to reach the target group. 

PMID- 23970389
TI  - ["Fit4You"--A Programme for Prevention and Reduction of Overweight in Apprentices
      in the Workplace Setting].
AB  - The effect of health promotion at the worksite for overweight adolescents is not
      known. This 2-year intervention study examined the effect of a multimodal
      programme including nutrition counselling, sport, and life-skill training on
      medical and psychological outcomes. The body mass index increased slightly less
      in the intervention group. Semistructured interviews at the end showed that
      participants are highly interested in health promotion at the worksite. 

PMID- 23970390
TI  - [Promotion of Mental Health in Early Childhood Institutions in Disadvantaged
      Areas].
AB  - A prevention programme for the promotion of psychological health was implemented
      in six early childhood education institutions, which caters to four different
      levels (courses for children, courses and counselling for parents, vocational
      training and supervision for paedagogic professionals, establishing networks
      within the social environment). New, low-threshold structures have been created
      in order to simplify the usage of prevention services and to develop meaningful
      connections between the support systems of health and education. The effects of
      the programme have been validated by means of a combination research design. 

PMID- 23970391
TI  - [Prevention of Obesity and Promotion of Healthy Nutrition in Children by a
      Kindergarten-Based Intervention: An Evaluation Study].
AB  - This outcome evaluation study has investigated different diet concepts in day
      care centres and their effects on health-related dietary behaviour of children
      and their families. No advantage of a certain approach to manage food and diet
      related activities in day-care centres could be shown. 

PMID- 23970392
TI  - [Barriers and Resources in Utilisation of HIV-Prevention Services for African
      Migrants].
AB  - The evaluation of the "Africa Project" investigates barriers to and resources of
      the utilisation of HIV-prevention services by African migrants. A KAP study
      evaluates knowledge, attitudes and practice of an African sample population (n =
      214). Results show that gender and cultural-psychological factors influence the
      perception of ways of infection and protection such as condom use and thereby
      determine the prerequisites for HIV prevention. 

PMID- 23970393
TI  - [The Preventive Home Visit as a Preventive Intervention to Reach the Elderly-
      Effectiveness and Cost-Effectiveness of Different Ways of Approach].
AB  - The aim of the study was a systematical further development of targeted
      approaches. Research questions were how elderly women and men could be motivated
      to participate in a preventive intervention and by which approaches elderly with
      different health risks could be reached. In several stages a specific
      motivational material was developed. Afterwards two different approaches to the
      elderly (general practice, health insurance) were tested and evaluated
      considering its (cost) effectiveness. 

PMID- 23970394
TI  - When EMA and FDA decisions conflict: differences in patients or in regulation?

PMID- 23970395
TI  - Malformations, genetic abnormalities, and Wilms tumor.
AB  - BACKGROUND: Wilms Tumor (WT) can occur in association with tumor predisposition
      syndromes and/or with clinical malformations. These associations have not been
      fully characterized at a clinical and molecular genetic level. This study aims to
      describe clinical malformations, genetic abnormalities, and tumor predisposition
      syndromes in patients with WT and to propose guidelines regarding indications for
      clinical and molecular genetic explorations. PROCEDURE: This retrospective study
      analyzed clinical abnormalities and predisposition syndromes among 295 patients
      treated for WT between 1986 and 2009 in a single pediatric oncological center.
      RESULTS: Clinically identified malformations and predisposition syndromes were
      observed in 52/295 patients (17.6%). Genetically proven tumor predisposition
      syndromes (n = 14) frequently observed were syndromes associated with alterations
      of the chromosome WT1 region such as WAGR (n = 6) and Denys-Drash syndromes (n =
      3), syndromes associated with alterations of the WT2 region (Beckwith-Wiedeman
      syndrome, n = 3), and Fanconi anemia (n = 2). Hemihypertrophy and genito-urinary
      malformations (n = 12 and n = 16, respectively) were the most frequently
      identified malformations. Other different syndromes or malformations (n = 10)
      were less frequent. Median age of WT diagnosis was significantly earlier for
      children with malformations than those without (27 months vs. 37 months, P =
      0.0009). There was no significant difference in terms of 5-year EFS and OS
      between WT patients without or with malformations. CONCLUSIONS: The frequency of
      malformations observed in patients with WT underline the need of genetic
      counseling and molecular genetic explorations for a better follow-up of these
      patients, with a frequently good outcome. A decisional tree, based on clinical
      observations of patients with WT, is proposed to guide clinicians for further
      molecular genetic explorations.

PMID- 23970396
TI  - Extramural extension as indicator for postoperative adjuvant chemotherapy in
      Stage IIA (pT3N0) colon cancer.
AB  - The usefulness of adjuvant chemotherapy (CMT) in patients with Stage IIA colon
      cancer remains unclear. The present study aimed to investigate extramural
      extension as an indicator for adjuvant CMT. Data were reviewed from 202
      consecutive patients with Stage IIA colon cancer that underwent curative surgery
      between 1995 and 2007. The distance of the extramural extension (DEE) was
      measured histologically. The optimal prognostic cut-off point of the DEE for
      oncologic outcomes was statistically determined. The eligible surviving patients
      had been followed for a median period of 75 months (range: 2-210 months).
      Patients were subdivided into two groups according to the optimal cut-off point;
      DEE <=5 mm (pT3a) and DEE >5 mm (pT3b). The pT3b was the most powerful
      independent risk factor for postoperative recurrence (P = 0.0324, HR: 3.04, 95%
      CI: 1.098-8.408), and was significantly correlated with distant metastasis (P =
      0.0161 HR: 5.19, 95% CI: 1.765-15.239). The recurrence-free and cancer-specific 5
      year survival rates in patients with pT3b were significantly lower than in
      patients with pT3a (81.5% vs. 95.4%, P = 0.0003 and 85.9% vs. 97.4%, P = 0.0007,
      respectively). pT3b could be an important risk factor for distant metastasis in
      Stage IIA colon cancer. Postoperative adjuvant CMT may be indicated for patients
      with pT3b.

PMID- 23970397
TI  - Multifunctional CNT-polymer composites for ultra-tough structural supercapacitors
      and desalination devices.
AB  - Pulsed electrodeposition of polyaniline (PANI) allows the fabrication of
      flexible, electrically conductive, nonwoven PANI-carbon nanotube (PANI-CNT)
      composite fabrics. They possess specific tensile strength and a modulus of
      toughness higher than that of aluminum matrix composites, titanium and aluminum
      alloys, steels, and many other structural materials. Electrochemical tests show
      that these nanocomposites additionally offer excellent cycle stability and ion
      electro-sorption and storage properties. 

PMID- 23970398
TI  - [What does Plastic Surgery?].

PMID- 23970399
TI  - [Comment to following article: Incisional hernias after median laparotomy. A
      concept for anatomic reconstruction of the abdominal wall by A. Wenger, B. Del
      Frari, H. Piza-Katzer, Handchir Mikrochir Plast Chir 2013; 45: 51-58].

PMID- 23970400
TI  - [The social background of male to female transsexuals].
AB  - Gender alignment surgery was introduced into German law in 1981. Judicial
      guidelines for the change of first names and gender were established and
      transsexuality was labelled as a psychosomatic and somatopsychic syndrome and
      disorder, thus opening the way for treatment to the social health-care under well
      defined conditions requesting cross-dressing and hormone therapy as well as
      psychological counselling by 2 independent psychologists or psychiatrists. In a
      retrospective, chart-related survey of questionnaires on male to female
      transsexuals it was found that patients start to suspect being born into the
      wrong gender at the onset of puberty, it takes them however approximately 20
      years to have gender alignment surgery. More than half the patients are single at
      this time, while the remaining group is married or divorced with equal rates. 68%
      regard themselves as heterosexual, 21% lesbian and 11% were undecided. About half
      the patients experienced support by their families for their decision. Despite
      numerous secondary corrections of the surgical alignment, patients were content
      with the result, although emotional acceptance of the desired result took about
      one year. In general plastic surgical gender alignment treatment was perceived as
      the major contribution to harmonise their phenotype with their identity. 

PMID- 23970401
TI  - [Comparison of cross face nerve graft with masseteric nerve as donor nerves for
      free functional muscle transfers in facial reanimation surgery].
AB  - Several surgical techniques have been proposed for the reconstruction of the
      smile in facial paralysis. The 2-stage approach utilising a cross-facial nerve
      graft (CFNG) and subsequent free functional muscle transfer represents the "gold
      standard". A single-stage alternative is the use of the masseteric nerve as donor
      nerve. Here we have retrospectively analysed the outcome of 8 patients who were
      treated with either of these procedures (4 per treatment group). We compared the
      oral commisure excursion between the 2 groups. Use of the masseteric nerve led to
      reinnervation of the muscle graft within 3 months. The 2-stage procedure required
      more than 12 months from the first procedure until first muscle contractions
      could be observed. A spontaneous smile could not be achieved in all patients when
      the masseteric nerve was used. The oral commisure excursion was symmetrical when
      compared to the healthy side in both groups, however the excursion was
      significantly higher in the masseteric nerve group compared to the CFNG group of
      patients. Most patients with the masseteric nerve as a donor nerve underwent a
      secondary procedure, which involved thinning of the muscle flap. In conclusion,
      the use of the masseteric nerve as a donor nerve for facial reanimation surgery
      is a single-stage alternative to the use of a CFNG as donor nerve. It delivers
      reliable results with strong muscle contractions with limitations in regard to
      achieving a spontaneous smile. 

PMID- 23970402
TI  - [Quality of life after brachial plexus lesions in adults].
AB  - Brachial plexus lesions are among the most severe injuries of the upper
      extremity. Despite intensive conservative and surgical treatment efforts,
      patients frequently suffer from serious impairments in the quality of life. This
      contribution presents the results of a retrospective clinical survey on the
      quality of life after brachial plexus injuries. Out of 38 treated patients, 25
      patients could be included in the study. The disability of arm, shoulder and hand
      was evaluated by the DASH score and the quality of life by the FLZm, a
      questionnaire on life satisfaction. In addition, demographic data, work situation
      and mechanism and type of injury were recorded. The examined patients were mainly
      young males who were injured in traffic, in particular motorcycle accidents. The
      DASH score analysis revealed that plexus injuries are among the most disabling
      injuries of the upper extremity. The associated restrictions in the different
      sections of the quality of life involve not only the health-related section but
      also partnership, family and leisure time activities. A strong relation between
      the possibility to return to work and the quality of life was found. We recommend
      the use of the DASH score and the FLZm questionnaire on life satisfaction as
      routine tools for the evaluation of the therapeutic outcome after brachial plexus
      injuries. 

PMID- 23970403
TI  - [Psychological aspects of breast reconstruction after breast cancer].
AB  - Breast cancer belongs to the most frequent cancer illnesses among women; a
      surgical therapy of this illness often encloses a complete or partial removal of
      the breast. Hence, the treatment can be very incriminating physically and
      psychically. Hencebreast reconstruction is an important step on the way back to a
      normal female body shape and to a normal life. Certificated breast centres are
      available nationwide and internationally for the best possible medical care for
      patients suffering from breast cancer; reconstruction of a natural breast form is
      looked today as a natural part of breast cancer treatment. The numerous methods
      which can be tuned individually to the situation of the woman are available for
      the reconstruction of the female breast. 

PMID- 23970404
TI  - [Commentary on "Traumatic stress disorder patients on the burn unit: noninvasive
      treatments and medication"].
AB  - It must be emphasized that the psychological management of patients with severe
      burn injuries always represents a major challenge that can never be carried out
      according to a general scheme but must in every case be adapted to the individual
      requirements and available options. 

PMID- 23970405
TI  - Antidepressant drugs as a complementary therapeutic strategy in cancer.
AB  - In the last decade, it has been increasingly recognized that antidepressant drugs
      may exert a range of effects, in addition to their well-documented ability to
      modulate neurotransmission. Although as a group they act on monoaminergic systems
      and receptors in different ways, a number of studies have demonstrated that at
      least some antidepressants might have other properties in common, including
      immunomodulatory, cyto/neuroprotective, analgesic and anti-inflammatory
      activities. These properties are partly related to the influence of
      antidepressants on glial cell function. Recently, emerging information about the
      possible anticancer properties of antidepressants has sparked increased interest
      within scientific community, and there is now evidence that these drugs affect
      the key cellular mechanisms of carcinogenesis. This review examines the putative
      cellular targets for the anticancer action of antidepressant drugs, and presents
      examples of the interaction between antidepressants and anticancer drugs. By
      reviewing the current state of research in this area, we hope to focus the
      attention of oncologists and researchers engaged in the study of cancer on the
      role that antidepressant drugs could play in the complementary therapy of cancer.

PMID- 23970406
TI  - Pyridoxamine, an inhibitor of protein glycation, in relation to microalbuminuria
      and proinflammatory cytokines in experimental diabetic nephropathy.
AB  - Diabetic nephropathy (DN) is one of the major complications that develop as
      consequence of chronic and uncontrolled hyperglycaemia. Hyperglycaemia initiates
      various processes, one of which is protein glycation, leading to the formation of
      advanced glycation end products. Alteration of intracellular signalling, gene
      expression, release of proinflammatory molecules and free radicals are examples
      of such changes and they contribute to the initiation of diabetic complications.
      In the current manuscript, we studied the effect of pyridoxamine (PM) on protein
      glycation, oxidative stress, interleukin-1alpha (IL-1alpha), IL-6, C-reactive
      protein (CRP), gene expression of tumour necrosis factor-alpha (TNF-alpha) and
      transforming growth factor-beta1 (TGF-beta1) in relation to microalbuminuria and
      kidney functions in a model of alloxan-induced diabetic rats. We have observed
      that onset of microalbuminuria has preceded the gradual increase of blood sugar
      level in diabetic rats. In diabetic rats, gene expression of TNF-alpha and TGF
      beta1 recorded a gradual increase and marked increase was observed after one and
      two weeks of alloxan administration, in comparison with normal rats. PM induced
      significant decrease in kidney malondialdehyde content and the gene expression of
      TNF-alpha and TGF-beta1, in addition to levels of serum glucose, fructosamine,
      urea, creatinine, IL-1alpha, IL-6, CRP and urine microalbumin. Histopathological
      examination of kidney tissues showed certain improvements as compared with
      diabetic control. In conclusion, our results may provide a supporting evidence
      for the therapeutic benefit of PM in DN. 

PMID- 23970407
TI  - Depletion of RNA-binding protein RBM8A (Y14) causes cell cycle deficiency and
      apoptosis in human cells.
AB  - RBM8A (Y14) contains an RNA-binding motif and forms a tight heterodimer with
      Magoh. The heterodimer is known to be a member of the exon junction complex that
      forms on mRNA before export and it is required for mRNA metabolism processes such
      as splicing, mRNA export and nonsense-mediated mRNA decay. Recently, deficient
      cellular proliferation has been observed in RBM8A- or Magoh-depleted cells. These
      results prompted us to study the role of RBM8A in cell cycle progression of human
      tumour cells. The depletion of RBM8A in A549 cells resulted in poor cell survival
      and the accumulation of mitotic cells. After release from G1/S arrest induced by
      a double thymidine block, the RBM8A-silenced cells could not proceed to the next
      G1 phase beyond G2/M phase. Finally, the sub-G1 population increased and the
      apoptosis markers caspases 3/7 were activated. Silenced cells exhibited an
      increased frequency of multipolar or monopolar centrosomes, which may have caused
      the observed deficiency in cell cycle progression. Finally, silencing of either
      RBM8A or Magoh resulted in mutual downregulation of the other protein. These
      results illustrate that the RBM8A-Magoh mRNA binding complex is required for M
      phase progression and both proteins may be novel targets for anticancer therapy. 

PMID- 23970408
TI  - Extremely low-frequency electromagnetic fields induce neural differentiation in
      bone marrow derived mesenchymal stem cells.
AB  - Extremely low-frequency electromagnetic fields (ELF-EMF) affect numerous
      biological functions such as gene expression, cell fate determination and even
      cell differentiation. To investigate the correlation between ELF-EMF exposure and
      differentiation, bone marrow derived mesenchymal stem cells (BM-MSCs) were
      subjected to a 50-Hz electromagnetic field during in vitro expansion. The
      influence of ELF-EMF on BM-MSCs was analysed by a range of different analytical
      methods to understand its role in the enhancement of neural differentiation. ELF
      EMF exposure significantly decreased the rate of proliferation, which in turn
      caused an increase in neuronal differentiation. The ELF-EMF-treated cells showed
      increased levels of neuronal differentiation marker (MAP2), while early neuronal
      marker (Nestin) was down-regulated. In addition, eight differentially expressed
      proteins were detected in two-dimensional electrophoresis maps, and were
      identified using ESI-Q-TOF LC/MS/MS. Among them, ferritin light chain,
      thioredoxin-dependent peroxide reductase, and tubulin beta-6 chain were up
      regulated in the ELF-EMF-stimulated group. Ferritin and thioredoxin-dependent
      peroxide reductase are involved in a wide variety of functions, including Ca(2+)
      regulation, which is a critical component of neurodegeneration. We also observed
      that the intracellular Ca(2+) content was significantly elevated after ELF-EMF
      exposure, which strengthens the modulatory role of ferritin and thioredoxin
      dependent peroxide reductase, during differentiation. Notably, western blot
      analysis indicated significantly increased expression of the ferritin light chain
      in the ELF-EMF-stimulated group (0.60 vs. 1.08; P < 0.01). These proteins may
      help understand the effect of ELF-EMF stimulation on BM-MSCs during neural
      differentiation and its potential use as a clinically therapeutic option for
      treating neurodegenerative diseases. 

PMID- 23970409
TI  - Antioxidant and antigenotoxic role of recombinant human erythropoeitin against
      alkylating agents: cisplatin and mitomycin C in cultured Vero cells.
AB  - Cisplatin (CDDP) and mitomycin C (MMC), two alkylating agents used against
      various solid tumours, are a common source of acute kidney injury. Thus,
      strategies for minimizing CDDP and MMC toxicity are of a clinical interest. In
      this study, we aimed to investigate the protective role of recombinant human
      erythropoietin (rhEPO) against oxidative stress and genotoxicity induced by CDDP
      and MMC in cultured Vero cells. Three types of treatments were performed: (i)
      cells were treated with rhEPO 24 h before exposure to CDDP/MMC (pre-treatment),
      (ii) cells were treated with rhEPO and CDDP/MMC simultaneously (co-treatment),
      (iii) cells were treated with rhEPO 24 h after exposure to CDDP/MMC (post
      treatment). Our results showed that rhEPO decreased the reactive oxygen species
      levels, the malondialdehyde levels and ameliorated glutathione (reduced and
      oxidized glutathione) modulation induced by CDDP and MMC in cultured Vero cells.
      Furthermore, rhEPO administration prevented alkylating agents-induced DNA damage
      accessed by comet test. Altogether, our results suggested a protective role of
      rhEPO, against CDDP- and MMC-induced oxidative stress and genotoxicity,
      especially in pre-treatment condition. 

PMID- 23970410
TI  - Potential protective effect of biphasic electrical stimulation against growth
      factor-deprived apoptosis on olfactory bulb neural progenitor cells through the
      brain-derived neurotrophic factor-phosphatidylinositol 3'-kinase/Akt pathway.
AB  - Stem cell therapy may provide a therapeutic method for the replacement and
      regeneration of damaged neurons of the central nervous system. However, neural
      stem cells (NSCs) and neural precursor cells (NPCs) are especially vulnerable
      after transplantation due to a lack of sufficient growth factors at the
      transplant site. Electrical stimulation (ES) has recently been found to
      participate in the regulation of cell proliferation, growth, differentiation, and
      migration, but its underlying anti-apoptotic effects remain unclear. This study
      investigated the protective effects of biphasic electrical stimulation (BES) on
      olfactory bulb NPCs against growth factor-deprived apoptosis, examining the
      survival and apoptotic features of the cells. Differentiation was assessed by
      neuronal and glial markers. Brain-derived neurotrophic factor
      phosphatidylinositol 3'-kinase (BDNF)-PI3K/Akt pathway activation was determined
      by enzyme-linked immunosorbent assay and Western blot. The chemical inhibitor
      wortmannin was used to inhibit the PI3K/Akt pathway. BES exerts a protective
      effect against growth factor-deprived apoptosis in the NPCs. BES enhanced cell
      survival and decreased the apoptotic/necrotic rate. Expression of phosphorylated
      Akt and BDNF secretion increased with BES for 12 h. Furthermore, the protective
      effects of BES were inhibited by blocking PI3K/AKT signalling. These results
      suggest that BES prevents growth factor-deprived apoptosis through the BDNF
      PI3K/Akt signalling. This work strengthens the opinion that BES may be used as an
      auxiliary strategy for improving cell survival and preventing cell apoptosis in
      stem cell-based transplantation therapy. 

PMID- 23970411
TI  - Human umbilical cord mesenchymal stem cells attenuate cisplatin-induced acute and
      chronic renal injury.
AB  - Mesenchymal stem cell is becoming a promising candidate in acute kidney injury
      (AKI). We first reported that human umbilical cord mesenchymal stem cells
      (hucMSCs) could ameliorate renal function in ischemic/reperfusion AKI rats, but
      the role of hucMSCs in cisplatin-induced acute and chronic injury has been
      demonstrated. More specifically, it is still unknown whether hucMSCs halt renal
      interstitial fibrosis. In this study, we investigated the effect of hucMSCs in
      cisplatin-induced kidney injury and explored the mechanism of action. Blood urea
      nitrogen (BUN) and creatinine (Cr) analyses showed amelioration of functional
      parameters in hucMSC-treated rats at early damage. Transplantation with hucMSCs
      promoted renal cell regeneration, inhibited cell apoptosis, abrogated
      inflammatory responses and protected mitochondria. Moreover, Masson's trichrome
      staining demonstrated reduced levels of fibrosis in kidney tissues of hucMSC
      treated rats at six and eight weeks after cisplatin injection. These results were
      corroborated by reduced collagen deposit, the ratio of Bax to Bcl-2 and
      transforming growth factor beta mRNA expression. Furthermore, hucMSCs prevented
      the epithelial-mesenchymal transition (EMT) in injury renal tissues, leading to
      the attenuation of chronic renal interstitial fibrosis. Taken together, our
      findings suggested that hucMSCs could decrease the kidney from development of
      later renal interstitial fibrosis by amelioration of early AKI. 

PMID- 23970412
TI  - Germany is first European country to recognise third sex on birth certificates.

PMID- 23970413
TI  - Long-term results of the combination of the N7 induction chemotherapy and the
      busulfan-melphalan high dose chemotherapy.
AB  - BACKGROUND: To evaluate long-term survival of the first cohort of stage-4
      neuroblastoma patients treated with the N7 induction chemotherapy, surgery of the
      primary tumor and high-dose chemotherapy (HDC) containing Busulfan-Melphalan (Bu
      Mel) followed by autologous stem cell transplantation (ASCT). PROCEDURE: From
      1998 to 1999, 47 children were included in the NB97 trial and treated with
      induction chemotherapy according to the N7 protocol, followed by surgery of the
      primary tumor. HDC (Busulfan, 600 mg/m(2) Melphalan, 140 mg/m(2) ) was
      administered in patients with partial response of metastases with no more than 3
      mIBG spots. Radiotherapy was delivered to the primary tumor site when tumors
      displayed MYCN amplification. RESULTS: Thirty-nine patients received Bu-Mel
      (83%): 23 who had achieved complete response (CR) of metastases, 20 after
      induction treatment and 3 after second-line chemotherapy, and 16 in partial
      response (PR). The toxicity of the whole treatment was manageable. The main HDC
      related-toxicity was hepatic veno-occlusive disease grade > 2 occurring in 15% of
      the patients. The 8-year EFS of the whole cohort was 34% (95% CI, 22-48%). The 8
      year EFS of the 39 patients who received Bu-Mel and ASCT was 41% (95% CI, 27
      57%). Patients who achieved a CR of metastases at the end of induction
      chemotherapy had a significantly better outcome than the others (8-year EFS, 52%
      vs. 20%; P = 0.02). CONCLUSIONS: The long-term results of this first prospective
      cohort of patients with metastatic disease treated with the N7 induction
      chemotherapy and HDC (Bu-Mel) confirm published data with stable survival curves
      but with a longer follow-up.

PMID- 23970414
TI  - Senescence at a glance.
AB  - Cellular senescence is a stable proliferation arrest that is associated with
      extensive cellular remodelling and an altered secretory pathway. Through its
      numerous inducers that lead to altered gene expression, senescence is able to
      influence many contrasting functions and pathologies, namely tumour suppression,
      tumour promotion, wound healing and ageing. As senescence is able to control such
      important tissue functions, it is now being pinpointed as a possible route for
      novel therapies. This article and accompanying poster aim to provide a summary of
      the initiators, pathways and roles of senescence, as well as present examples of
      senescence and a possible use for senescence in therapy. 

PMID- 23970415
TI  - Syndecan-4 signaling at a glance.
AB  - Syndecan-4, a ubiquitous cell surface proteoglycan, mediates numerous cellular
      processes through signaling pathways that affect cellular proliferation,
      migration, mechanotransduction and endocytosis. These effects are achieved
      through syndecan-4 functioning as both a co-receptor for the fibroblast growth
      factor receptors (FGFR1-FGFR4) and its ability to independently activate
      signaling pathways upon ligand binding. As an FGFR co-receptor, syndecan-4
      strengthens the duration and intensity of downstream signaling upon ligand
      binding; this is particularly evident with regard to mitogen-activated protein
      kinase (MAPK) signaling. In contrast, syndecan-4 also functions as an independent
      receptor for heparin-binding growth factors, such as fibroblast growth factors
      (FGFs), vascular endothelial growth factors (VEGFs) and platelet-derived growth
      factors (PDGFs). These signaling cascades affect canonical signaling components,
      such as the mammalian target of rapamycin (mTOR), AKT1 and the Rho family of
      GTPases. In combination with the integrin family of proteins, syndecan-4 is also
      able to form physical connections between the extracellular matrix (ECM) and
      cytoskeletal signaling proteins, and it has a key role in regulation of integrin
      turnover. This unique versatility of the interactions of syndecan-4 is
      characterized in this Cell Science at a Glance article and illustrated in the
      accompanying poster. 

PMID- 23970416
TI  - DNA asymmetry in stem cells - immortal or mortal?
AB  - The immortal strand hypothesis proposes that stem cells retain a template copy of
      genomic DNA (i.e. an 'immortal strand') to avoid replication-induced mutations.
      An alternative hypothesis suggests that certain cells segregate sister chromatids
      non-randomly to transmit distinct epigenetic information. However, this area of
      research has been highly controversial, with conflicting data even from the same
      cell types. Moreover, historically, the same term of 'non-random sister chromatid
      segregation' or 'biased sister chromatid segregation' has been used to indicate
      distinct biological processes, generating a confusion in the biological
      significance and potential mechanism of each phenomenon. Here, we discuss the
      models of non-random sister chromatid segregation, and we explore the strengths
      and limitations of the various techniques and experimental model systems used to
      study this question. We also describe our recent study on Drosophila male
      germline stem cells, where sister chromatids of X and Y chromosomes are
      segregated non-randomly during cell division. We aim to integrate the existing
      evidence to speculate on the underlying mechanisms and biological relevance of
      this long-standing observation on non-random sister chromatid segregation. 

PMID- 23970417
TI  - Centrosomal protein CEP104 (Chlamydomonas FAP256) moves to the ciliary tip during
      ciliary assembly.
AB  - The ciliary tip has been implicated in ciliary assembly and disassembly, and
      signaling, yet information on its protein composition is limited. Using
      comparative, quantitative proteomics based on the fact that tip proteins will be
      approximately twice as concentrated in half-length compared with full-length
      flagella, we have identified FAP256 as a tip protein in Chlamydomonas. FAP256
      localizes to the tips of both central pair and outer doublet microtubules (MTs)
      and it remains at the tip during flagellar assembly and disassembly. Similarly,
      its vertebrate counterpart, CEP104, localizes on the distal ends of both
      centrioles of nondividing cells until the mother centriole forms a cilium and
      then localizes at the tip of the elongating cilium. A null mutant of FAP256 in
      Chlamydomonas and RNAi in vertebrate cells showed that FAP256/CEP104 is required
      for ciliogenesis in a high percentage of cells. In those cells that could form
      cilia, there were structural deformities at the ciliary tips.

PMID- 23970418
TI  - A Serrate-Notch-Canoe complex mediates essential interactions between glia and
      neuroepithelial cells during Drosophila optic lobe development.
AB  - It is firmly established that interactions between neurons and glia are
      fundamental across species for the correct establishment of a functional brain.
      Here, we found that the glia of the Drosophila larval brain display an essential
      non-autonomous role during the development of the optic lobe. The optic lobe
      develops from neuroepithelial cells that proliferate by dividing symmetrically
      until they switch to asymmetric/differentiative divisions that generate
      neuroblasts. The proneural gene lethal of scute (l'sc) is transiently activated
      by the epidermal growth factor receptor (EGFR)-Ras signal transduction pathway at
      the leading edge of a proneural wave that sweeps from medial to lateral
      neuroepithelium, promoting this switch. This process is tightly regulated by the
      tissue-autonomous function within the neuroepithelium of multiple signaling
      pathways, including EGFR-Ras and Notch. This study shows that the Notch ligand
      Serrate (Ser) is expressed in the glia and it forms a complex in vivo with Notch
      and Canoe, which colocalize at the adherens junctions of neuroepithelial cells.
      This complex is crucial for interactions between glia and neuroepithelial cells
      during optic lobe development. Ser is tissue-autonomously required in the glia
      where it activates Notch to regulate its proliferation, and non-autonomously in
      the neuroepithelium where Ser induces Notch signaling to avoid the premature
      activation of the EGFR-Ras pathway and hence of L'sc. Interestingly, different
      Notch activity reporters showed very different expression patterns in the glia
      and in the neuroepithelium, suggesting the existence of tissue-specific factors
      that promote the expression of particular Notch target genes or/and a reporter
      response dependent on different thresholds of Notch signaling.

PMID- 23970419
TI  - Pin1 acts as a negative regulator of the G2/M transition by interacting with the
      Aurora-A-Bora complex.
AB  - Pin1 was the first prolyl isomerase identified that is involved in cell division.
      The mechanism by which Pin1 acts as a negative regulator of mitotic activity in
      G2 phase remains unclear. Here, we found that Aurora A can interact with and
      phosphorylate Pin1 at Ser16, which suppresses the G2/M function of Pin1 by
      disrupting its binding ability and mitotic entry. Our results also show that
      phosphorylation of Bora at Ser274 and Ser278 is crucial for binding of Pin1.
      Through the interaction, Pin1 can alter the cytoplasmic translocation of Bora and
      promote premature degradation by beta-TrCP, which results in a delay in mitotic
      entry. Together with the results that Pin1 protein levels do not significantly
      fluctuate during cell-cycle progression and Aurora A suppresses Pin1 G2/M
      function, our data demonstrate that a gain of Pin1 function can override the
      Aurora-A-mediated functional suppression of Pin1. Collectively, these results
      highlight the physiological significance of Aurora-A-mediated Pin1 Ser16
      phosphorylation for mitotic entry and the suppression of Pin1 is functionally
      linked to the regulation of mitotic entry through the Aurora-A-Bora complex.

PMID- 23970421
TI  - A BDOPV-based donor-acceptor polymer for high-performance n-type and oxygen-doped
      ambipolar field-effect transistors.
AB  - An electron-deficient building block BDOPV is developed to construct a new donor
      acceptor conjugated polymer BDOPV-2T for high-performance n-type and oxygen-doped
      ambipolar polymer field-effect transistors. A high electron mobility up to 1.74
      cm(2) V(-1) s(-1) is demonstrated under ambient conditions. Furthermore, the
      oxygen-doping effect and possible mechanism are discussed. 

PMID- 23970420
TI  - Prognostic implications of serum microRNA-21 in colorectal cancer.
AB  - BACKGROUND AND OBJECTIVES: MicroRNAs (miRNAs) are small, noncoding RNAs that are
      involved in carcinogenesis through postranscriptional gene regulatory activity.
      Few studies have focused on the detection of miR-21 in serum rather than in
      tissue. The current study aimed to measure serum miR-21 expression levels and to
      evaluate their association with the outcome of colorectal cancer (CRC). METHODS:
      Blood samples were collected from 102 CRC patients undergoing surgery with
      curative intent. The expression levels of miR-21 were measured using a
      quantitative reverse transcription polymerase chain reaction (qRT-PCR). The
      results were analysed to assess the relationship between serum miR-21 levels and
      patient survival. RESULTS: A univariate analysis revealed that lower expression
      levels of serum miR-21 were associated with higher local recurrence (P = 0.025)
      and mortality (P = 0.029). A logistic regression analysis demonstrated that the
      relative overexpression of miR-21 (expression > 1) was associated with a 51%
      reduction in the risk of recurrence. A Cox regression analysis identified miR-21
      expression as an independent predictor of survival (P = 0.048); a relative
      increase in miR-21 expression (>1) was associated with a 50% reduction in the
      risk of mortality. CONCLUSION: The expression level of serum miR-21 correlates
      with the recurrence and mortality of CRC patients. Our results suggest that
      circulating serum miR-21 is a promising prognostic tumour marker, and they
      highlight the potential clinical utility of miR-21 expression as a prognostic
      marker for CRC prognosis.

PMID- 23970422
TI  - New alkaloids from Pancratium maritimum.
AB  - As a part of ongoing search efforts for the discovery of anticancer lead entities
      from natural sources, bulbs and flowers of the amaryllidaceous plant Pancratium
      maritimum have been investigated. Fractionation of the extracts of the fresh
      flowers and bulbs of P. maritimum led to the isolation of four new alkaloids,
      namely pancrimatines A (1) and B (2), norismine (3), and pancrimatine C (4),
      together with the previously reported N-methyl-8,9-methylenedioxy-6
      phenanthridone (5), trispheridine (6), and N-methyl-8,9
      methylenedioxyphenanthridine (7). The structures of these alkaloids were
      established on the basis of extensive 1D and 2D NMR and high-resolution mass
      spectral analyses as well as comparison with the literature. Compounds 2 and 7
      showed antiproliferative and antimigratory activity against the highly metastatic
      human prostate cancer cell line PC-3 cells without cytotoxicity. The
      phenanthridine alkaloid class was identified as having potential for use to
      control prostate cancer proliferation and migration. 

PMID- 23970423
TI  - Phenolic compounds with in vitro activity against respiratory syncytial virus
      from the Nigerian lichen Ramalina farinacea.
AB  - The extract of the Nigerian lichen Ramalina farinacea showed inhibitory activity
      against the respiratory syncytial virus in a preliminary assay. A follow-up
      chemical investigation of this lichen led to the isolation of thirteen phenolic
      compounds (1-13), including one new hydroquinone depside, designated 5
      hydroxysekikaic acid (1), and one new orsellinic acid derivative, 2,3-dihydroxy-4
      methoxy-6-pentylbenzoic acid (8). Their structures were unambiguously determined
      by analysis of 1D and 2D NMR and mass spectroscopic data, as well as by
      comparison with literature data. Compound 1 was found to partially convert to a
      1,4-benzoquinone derivative (1a) during storage. The antiviral activities of the
      isolated compounds were evaluated against the respiratory syncytial virus. Among
      them, sekikaic acid (2) showed potent inhibition towards a recombinant strain rg
      respiratory syncytial virus (IC50 5.69 ug/mL) and respiratory syncytial virus A2
      strain (IC50 7.73 ug/mL). The effect of sekikaic acid on the cell viability of
      HEp2 and Vero cell lines was investigated, and the time of addition assay
      revealed that sekikaic acid clearly interferes with viral replication at a viral
      post-entry step, which is over 1.3-fold more active than the control ribavirin at
      4 hours postinfection addition. Furthermore, sekikaic acid did not display
      virucidal activity at concentrations below the TC50, whereas the parental extract
      did.

PMID- 23970424
TI  - Characterization of in vitro ADME properties of diosgenin and dioscin from
      Dioscorea villosa.
AB  - Dioscorea villosa (wild yam) is native to North America and has been widely used
      as a natural alternative for estrogen replacement therapy to improve women's
      health as well as to treat inflammation, muscle spasm, and asthma. Diosgenin and
      dioscin (glycoside form of diosgenin) are reported to be the pharmacologically
      active compounds. Despite the reports of significant pharmacological properties
      of dioscin and diosgenin in conditions related to inflammation, cancer, diabetes,
      and gastrointestinal ailments, no reports are available on ADME properties of
      these compounds. This study was carried out to determine ADME properties of
      diosgenin and dioscin and their effects on major drug metabolizing enzymes (CYP
      3A4, 2D6, 2C9, and 1A2). The stability was determined in simulated gastric and
      intestinal fluids (SGF, pH 1.2 and SIF, pH 6.8), and intestinal transport was
      evaluated in Caco-2 model. Phase I and phase II metabolic stability was
      determined in human liver microsomes and S9 fractions, respectively. Quantitative
      analysis of dioscin and diosgenin was performed by UPLC-MS system. Dioscin
      degraded up to 28.3 % in SGF and 12.4 % in SIF, which could be accounted for by
      its conversion to diosgenin (24.2 %. in SGF and 2.4 % in SIF). The depletion of
      diosgenin in SGF and SIF was < 10 %. Diosgenin was stable in HLM but disappeared
      in S9 fraction with a half-life of 11.3 min. In contrast, dioscin was stable in
      both HLM and S9 fractions. Dioscin showed higher permeability across Caco-2
      monolayer with no significant efflux, while diosgenin was subjected to efflux
      mediated by P-glycoprotein. Diosgenin and dioscin inhibited CYP3A4 with IC50
      values of 17 and 33 uM, respectively, while other CYP enzymes were not affected.
      In conclusion, dioscin showed better intestinal permeability. Conversion of
      dioscin to diosgenin was observed in both gastric and intestinal fluids. No phase
      I metabolism was detected for both compounds. The disappearance of diosgenin in
      S9 fraction indicated phase II metabolism. 

PMID- 23970425
TI  - Protective effect of apocynin in a mouse model of chemically-induced colitis.
AB  - Apocynin, a constituent of Picrorhiza kurroa, successfully inhibits NADPH oxidase
      and shows promise as an anti-inflammatory drug. Now, we report anti-inflammatory
      effects of apocynin in an experimental colitis model induced by dextran sulfate
      sodium as well as the effects on the mediators involved in this process. Apocynin
      reduced the colitis induced in mice by administration of 5 % dextran sulfate
      sodium during 7 days. Mice were fed a control diet or a diet supplemented with 2
      % of apocynin or 2 % of rutin. Sulfasalazine (50 mg/kg, p. o.) was used as a
      positive control. Treatment with apocynin and rutin ameliorated the course of
      colonic inflammation with results similar to those of the reference drug, as
      could be seen by reductions in the disease activity index scores and colon
      length. NO and PGE2 production as well as the iNOS and COX-2 expression were
      reduced by apocynin and rutin. Moreover, the activation of NF-kappaB p65 as well
      as STAT3 in dextran sulfate sodium-treated colon tissues was significantly
      reduced by apocynin. These results are promising for further experimental studies
      on treating gastrointestinal diseases and on the potential protective effects of
      apocynin. 

PMID- 23970426
TI  - Neolignans from the fruits of Magnolia obovata and their inhibition effect on NO
      production in LPS-induced RAW 264.7 cells.
AB  - Three new neolignans, named 9-methoxyobovatol (6), magnobovatol (7), and 2
      hydroxyobovaaldehyde (9), along with six known ones, magnolol (1), honokiol (2),
      isomagnolol (3), obovatol (4), obovatal (5), and obovaaldehyde (8), were isolated
      from the fruits of Magnolia obovata using silica gel and ODS column
      chromatography. From the results of spectroscopic data including EIMS, IR, 1H-
      and 13C-NMR, DEPT, and 2D-NMR (gCOSY, gHSQC, gHMBC), the chemical structures were
      determined. All isolated compounds were evaluated for inhibition activity on
      nitric oxide production in LPS-induced RAW 264.7 cells, and compounds 1-4, 6, 7,
      and 9 showed significant activity with IC50 values of 15.8 +/- 0.3, 3.3 +/- 1.2,
      14.1 +/- 0.9, 6.2 +/- 1.2, 14.8 +/- 2.3, 14.2 +/- 1.2, and 14.8 +/- 3.2 uM,
      respectively, without any visible toxic effect. 

PMID- 23970431
TI  - Could environmental exposures facilitate the incidence of addictive behaviors?

PMID- 23970432
TI  - Identification of practices and morbidities affecting the mortality of very low
      birth weight infants using a multilevel logistic analysis: clinical trial or
      standardisation?
AB  - OBJECTIVES: To determine the feasibility of clinical trials of newly developed
      treatments or standardisation of existing practices to further improve outcomes
      among very low birth weight (VLBW) infants, a nationwide database was analysed
      with a two-dimensional approach using two multivariate logistic models. DESIGN:
      Retrospective observational analysis. SETTING: Level III perinatal centres in
      Japan. PARTICIPANTS: 15 920 VLBW infants admitted at 38 participating centres
      from 2003 through 2010. OUTCOME MEASURES: Clinical information for the infants
      was collected until discharge from the centres. A multivariate logistic model
      identified practices and morbidities associated with mortality. Then, those which
      were significantly associated with mortality were analysed using a multilevel
      logistic model. The residues calculated by the multilevel analysis were used as
      an indicator of centre variation. RESULTS: Among practices, antenatal steroids
      and intubation at birth showed relatively high centre variations (0.9 and 0.8)
      and favourable ORs (0.7 and 0.5) for mortality, while caesarean section showed a
      low centre variation (0.4) and a favourable OR (0.8). Sepsis and air leak showed
      high centre variations (0.4 and 0.4) and high ORs (3.8 and 3.4) among
      morbidities. Pulmonary haemorrhage, persistent pulmonary hypertension of the
      newborn, and intraventricular haemorrhage showed moderate variations (0.2, 0.3
      and 0.2, respectively) and high ORs (5.6, 4.1 and 2.9, respectively). In
      contrast, necrotising enterocolitis showed the lowest variation (0.1) and a high
      OR (4.9). CONCLUSIONS: The two-dimensional approach has clearly demonstrated the
      importance of clinical trial or standardisation. The practices and morbidities
      with low centre variations and high ORs for mortality must be improved through
      clinical trials of newly introduced techniques, while standardisation must be
      considered for practices and morbidities with a high centre variation. TRIAL
      REGISTRATION: The database was registered as UMIN000006961.

PMID- 23970434
TI  - Effects of polymorphisms of the SLCO2B1 transporter gene on the pharmacokinetics
      of montelukast in humans.
AB  - Montelukast, a leukotriene receptor antagonist, is a substrate of organic anion
      transporting OATP2B1 encoded by the SLCO2B1. We evaluated the effects of six non
      synonymous (c.1175C>T, c.1457C>T, c.43C>T, c.935G>A, c.601G>A, and c.644A>T)
      polymorphisms and one promoter (g.-282G>A) polymorphism on the pharmacokinetics
      of montelukast. A single dose of 10 mg montelukast was administered in 24 healthy
      subjects. Its levels were measured up to 24 hours and a pharmacokinetic analysis
      was performed based on the SLCO2B1 polymorphisms. We did not encounter subjects
      with c.1175C>T, c.43C>T, or c.644A>T polymorphisms. The remaining SLCO2B1
      polymorphisms did not affect plasma levels of montelukast, and pharmacokinetic
      parameters of montelukast did not differ among genotype groups. Oral clearance
      results were as follows: (1) 3.3 L/h for c.935GG, 3.0 L/h for c.935GA, and 3.5
      L/h for c.935AA; (2) 3.4 L/h for c.1457CC, 2.9 L/h for c.1457CT, and 3.2 L/h for
      c.1457TT; (3) 3.2 L/h for c.601GG, 3.4 L/h for c.601GA, and 3.4 L/h for c.601AA;
      (4) 3.2 L/h for g.-282GG, 3.4 L/h for g.-282GA, and 3.2 L/h for g.-282AA. The
      findings suggest that SLCO2B1 polymorphisms do not affect the pharmacokinetics of
      montelukast and that SLCO2B1 polymorphisms appear to be a minor determinant of
      inter-individual variability of montelukast. 

PMID- 23970433
TI  - Comparison of Latino and non-Latino patients with Ewing sarcoma.
AB  - BACKGROUND: Ewing sarcoma (ES) is a malignancy of bone and soft tissue in
      children and adults. Previous registry-based studies indicate that Latino
      patients with ES have inferior outcomes compared to non-Latino patients, though
      an etiology for this difference could not be identified. To explore possible
      differences that might underlie this disparity, we conducted a retrospective
      study to compare clinical characteristics, tumor features, healthcare access, and
      treatment outcomes between Latino and non-Latino patients with ES. METHODS:
      Primary data for 218 ES patients treated at two academic medical centers between
      1980 and 2010 were collected. Categorical data were compared using Fisher exact
      tests; Wilcoxon rank-sum tests were used for continuous variables. Survival was
      estimated using Kaplan-Meier analysis and compared using log-rank testing.
      RESULTS: Latino patients were diagnosed at a younger age (P = 0.014). All other
      clinical and histological data were similar between groups, including radiologic
      and histologic response to neoadjuvant chemotherapy. Latino patients had lower
      socioeconomic status (P = 0.001), were less likely to have insurance (P = 0.001),
      and were more likely to present to the emergency room at onset of symptoms (P =
      0.031) rather than to primary care physicians. Five-year event free survival
      (EFS) and overall survival (OS) were similar between Latino and non-Latino
      patients (EFS: 60.5% vs. 50.9% P = 0.37; OS: 77.6% vs. 68.6% P = 0.54).
      CONCLUSION: Latino patients with ES present at a younger age, and have evidence
      of impaired access to healthcare. Response to initial therapy appears similar
      between Latino and non-Latino patients.

PMID- 23970435
TI  - Assembly of thiometalate-based {Mo16 } and {Mo36 } composite clusters combining
      [Mo2O2S2 ](2+) cations and selenite anions.
AB  - A new family of thiometalate-based composite molecular materials is synthesized
      and characterized. 1.6 and 1.9 nm-sized clusters are observed in the gas phase
      utilizing high-resolution ESI-MS. The diversity of the selenite anions as an
      inorganic ligand is demonstrated by the isolation of the highest nuclearity
      selenium-based oxothiometalate materials reported so far. The observed proton
      conductivity of the selenite based oxothiometalate species renders them as
      promising alternative materials for fuel-cell applications. 

PMID- 23970436
TI  - Race-contingent face aftereffects: a result of perceived racial typicality, not
      categorization.
AB  - Opposing aftereffects can be simultaneously induced by adapting to faces of
      different races distorted in opposite directions, allowing researchers to infer
      that faces are encoded against race-specific prototypes. This effect also
      suggests the existence of dissociable pools of neurons sensitive to race, each of
      which has been differently adapted to cause an opposite aftereffect. More recent
      studies have suggested that changes in the strength of race-contingent
      aftereffects reveal evidence of categorical perception, as they are larger when
      the adapting faces straddle the racial category boundary. We examined whether
      changes in these effects more closely correspond to a dichotomous categorical
      judgment, reflecting highly race-selective neural mechanisms, or more continuous
      perceptions of racial typicality, reflecting visual channels that are more
      broadly tuned. In Experiment 1, faces with a range of "morph levels" (i.e.,
      relative contributions of Asian/Caucasian faces) were either rated on a
      continuous scale for Asian/Caucasian typicality, or simply categorized as
      Asian/Caucasian. As expected, typicality ratings showed a shallow slope
      (observers were sensitive to morph level over a broad range), while dichotomous
      racial categorization showed a steep slope (a rapid switch from categorization as
      Asian-Caucasian). In Experiment 2, race-contingent adaptation was assessed using
      test faces with various morph levels. Aftereffect size showed a shallow slope,
      closely resembling the racial typicality ratings, but showing a significant
      difference to the categorization data. This suggests that although the visual
      channels processing these faces do show some selectivity to race, they are
      sensitive to perceptions of racial typicality, showing a gradual transition of
      activity across a broad range of faces along the racial continuum. 

PMID- 23970437
TI  - A systematic review of instruments that assess the implementation of hospital
      quality management systems.
AB  - PURPOSE: Health-care providers invest substantial resources to establish and
      implement hospital quality management systems. Nevertheless, few tools are
      available to assess implementation efforts and their effect on quality and safety
      outcomes. This review aims to (i) identify instruments to assess the
      implementation of hospital quality management systems, (ii) describe their
      measurement properties and (iii) assess the effects of quality management on
      quality improvement and quality of care outcomes. DATA SOURCES: We performed a
      systematic literature search from 1990 to 2011 in PubMed, CINAHL, EMBASE,
      Cochrane Library and Web of Science. In addition, we used snowball strategies,
      screened the reference lists of eligible papers, reviewed grey literature and
      contacted experts in the field. STUDY SELECTION: and data extraction Two
      reviewers screened eligible papers based on pre-defined inclusion and exclusion
      criteria and all authors extracted data. Eligible papers are described in terms
      of general characteristics (settings, type and level of respondents, mode of data
      collection), methodological properties (sampling strategy, item derivation,
      conceptualization of quality management, assessment of reliability and validity,
      scoring) and application/implementation (accounting for context, organizational
      adaptations, sensitivity to change, deployment and effect size). RESULTS:
      Eighteen papers were deemed eligible for inclusion. While some common domains
      emerged in measurement conceptualization, substantial differences in scope
      persist. The instruments' measurement properties were insufficiently described
      and only few instruments assessed links between the implementation of quality
      management systems (QMS) and improvement strategies or outcomes. CONCLUSIONS:
      There is currently no well-established measure to assess the implementation and
      effectiveness of quality management systems. Future research should address this
      gap.

PMID- 23970438
TI  - DPM foot and ankle fellowships.

PMID- 23970439
TI  - Invited reply to "Treatment of pediatric hypomagnesaemia: a fast and safe way"
      (PBC-13-0655) by Ismail El-Beshlawi.

PMID- 23970440
TI  - Physical and mental fatigue as predictors of sickness absence among Norwegian
      nurses.
AB  - We investigated whether fatigue can be used to screen nursing populations for
      risk of sickness absence. Data were available from a prospective cohort study of
      2,059 Norwegian nurses working in hospital care, psychiatric care, and nursing
      home/home care settings. Physical and mental fatigue were measured at baseline
      with Chalder's Fatigue Questionnaire (FQ). Self-rated sickness absence at 1-year
      follow-up was considered high if nurses reported >30 sick days in the past year.
      Physical fatigue accurately predicted high sickness absence and adequately
      discriminated between high- and low-risk nurses in nursing home/home care
      settings. Mental fatigue was not predictive in any setting. The FQ is suitable
      for screening specific nursing populations for the risk of high sickness absence.

PMID- 23970441
TI  - Organic electrochemical transistor array for recording transepithelial ion
      transport of human airway epithelial cells.
AB  - An organic electrochemical transistor array is integrated with human airway
      epithelial cells. This integration provides a novel method to couple
      transepithelial ion transport with electrical current. Activation and inhibition
      of transepithelial ion transport are readily detected with excellent time
      resolution. The organic electrochemical transistor array serves as a promising
      platform for physiological studies and drug testing. 

PMID- 23970442
TI  - The effects of low levels of light at night upon the endocrine physiology of
      western scrub-jays (Aphelocoma californica).
AB  - Florida scrub-jays (Aphelocoma coerulescens) in the suburbs breed earlier than
      jays in native habitat. Amongst the possible factors that influence this advance
      (e.g., food availability, microclimate, predator regime, etc.), is exposure to
      artificial lights at night (LAN). LAN could stimulate the reproductive axis of
      the suburban jays. Alternatively, LAN could inhibit pineal melatonin (MEL), thus
      removing its inhibitory influence on the reproductive axis. Because Florida scrub
      jays are a threatened species, we used western scrub-jays (Aphelocoma
      californica) to investigate the effects of LAN upon reproductive hormones and
      melatonin. Jays were held under conditions in which the dark-phase of the
      light:dark cycle was without illumination and then under low levels of LAN. Under
      both conditions, birds were exposed first to short-days (9.5L:14.5D) that were
      gradually increased to long-days (14.5L:9.5D). At various times, blood samples
      were collected during the light part of the cycle to measure reproductive
      hormones (luteinizing hormone, LH; testosterone, T; and estradiol, E2 ).
      Similarly, samples to assess melatonin were collected during the dark. In males,
      LAN caused a depression in LH levels and levels were ~4* greater under long- than
      short-days. In females, there was no effect of LAN or photoperiod upon LH. LAN
      resulted in depressed T levels in females, although there was no effect on T in
      males. E2 levels in both sexes were lower under LAN than under an unlighted dark
      phase. Paradoxically, MEL was higher in jays under LAN, and under long-days. MEL
      did not differ by sex. LAN disrupted the extraordinarily strong correlation
      between T and E2 that existed under unlighted nocturnal conditions. Overall, our
      findings fail to support the hypothesis that LAN stimulates the reproductive
      axis. Rather, the data demonstrate that LAN tends to inhibit reproductive hormone
      secretion, although not in a consistent fashion between the sexes.

PMID- 23970443
TI  - Characterization of breathing patterns during patient-controlled opioid
      analgesia.
AB  - BACKGROUND: Respiratory rate is an important measurement in patient care, but
      accurate measurement is often difficult. We have developed a simple non-invasive
      device to measure respiratory movements in clinical circumstances, with minimal
      interference with the patient. We investigated respiratory patterns in patients
      receiving postoperative morphine analgesia to assess the capacity of the device
      to detect abnormalities. METHODS: We studied subjects during self-administered
      opioid analgesia after major gynaecological surgery, and related the derived
      signals with a signal from a nasal cannula. Respiratory movement signals were
      transmitted wirelessly to a recorder from two encapsulated tri-axial
      accelerometer (RESpeck) sensors. We analysed the signals using two different
      sensor placements, each for 30 min. The nasal cannula signal was used to classify
      breathing patterns as obstructive or non-obstructed. RESULTS: We studied 20
      patients for a mean duration of 49 min each. Breathing patterns were very
      variable, between and within patients. The median breathing rates ranged from 6.4
      to 19.5 bpm. Breathing was partly obstructed in 10 patients, and six patients had
      repeated cycles of obstruction and transient recovery. In these patients, we
      found a consistent and statistically significant pattern of changes in chest wall
      movement, with increased abdominal and decreased rib cage movement during
      obstruction. In patients with slow respiratory rates, breath-to-breath times were
      highly variable. CONCLUSIONS: In undisturbed subjects receiving patient
      controlled morphine analgesia after surgery, abnormal breathing patterns are
      extremely common. Cyclical airway obstruction is frequent and associated with a
      typical pattern of changes in chest wall movement.

PMID- 23970444
TI  - High-dose chemotherapy and autologous haematopoietic stem cell rescue for
      children with high-risk neuroblastoma.
AB  - BACKGROUND: Despite the development of new treatment options, the prognosis of
      high-risk neuroblastoma patients is still poor; more than half of patients
      experience disease recurrence. High-dose chemotherapy and haematopoietic stem
      cell rescue (i.e. myeloablative therapy) might improve survival. This review is
      an update of a previously published Cochrane review. OBJECTIVES: The primary
      objective was to compare the efficacy of myeloablative therapy with conventional
      therapy in children with high-risk neuroblastoma. Secondary objectives were to
      determine possible effects of these interventions on adverse events, late effects
      and quality of life. SEARCH METHODS: We searched the electronic databases CENTRAL
      (The Cochrane Library 2012, issue 6), MEDLINE/PubMed (1966 to June 2012) and
      EMBASE/Ovid (1980 to June 2012). In addition, we searched reference lists of
      relevant articles and the conference proceedings of the International Society for
      Paediatric Oncology (SIOP) (from 2002 to 2011), American Society for Pediatric
      Hematology and Oncology (ASPHO) (from 2002 to 2012), Advances in Neuroblastoma
      Research (ANR) (from 2002 to 2012) and American Society for Clinical Oncology
      (ASCO) (from 2008 to 2012). We searched for ongoing trials by scanning the ISRCTN
      register and the National Institute of Health Register (http://www.controlled
      trials.com; both screened July 2012). SELECTION CRITERIA: Randomised controlled
      trials (RCTs) comparing the efficacy of myeloablative therapy with conventional
      therapy in high-risk neuroblastoma patients. DATA COLLECTION AND ANALYSIS: Two
      authors independently performed study selection, data extraction and risk of bias
      assessment. If appropriate, we pooled studies. The risk ratio (RR) and 95%
      confidence interval (CI) was calculated for dichotomous outcomes. For the
      assessment of survival data, we calculated the hazard ratio (HR) and 95% CI. We
      used Parmar's method if hazard ratios were not reported in the study. We used a
      random-effects model. MAIN RESULTS: We identified three RCTs including 739
      children. They all used an age of one year as the cut-off point for pre-treatment
      risk stratification. The updated search identified a manuscript reporting
      additional follow-up data for one of these RCTs. There was a statistically
      significant difference in event-free survival in favour of myeloablative therapy
      over conventional chemotherapy or no further treatment (3 studies, 739 patients;
      HR 0.78, 95% CI 0.67 to 0.90). There was a statistically significant difference
      in overall survival in favour of myeloablative therapy over conventional
      chemotherapy or no further treatment (2 studies, 360 patients; HR 0.74, 95% CI
      0.57 to 0.98). However, when additional follow-up data were included in the
      analyses the difference in event-free survival remained statistically significant
      (3 studies. 739 patients; HR 0.79, 95% CI 0.70 to 0.90), but the difference in
      overall survival was no longer statistically significant (2 studies, 360
      patients; HR 0.86, 95% CI 0.73 to 1.01). The meta-analysis of secondary malignant
      disease and treatment-related death did not show any statistically significant
      differences between the treatment groups. Data from one study (379 patients)
      showed a significantly higher incidence of renal effects, interstitial
      pneumonitis and veno-occlusive disease in the myeloablative group compared to
      conventional chemotherapy, whereas for serious infections and sepsis no
      significant difference between the treatment groups was identified. No
      information on quality of life was reported. In the individual studies we
      evaluated different subgroups, but the results were not univocal in all studies.
      All studies had some methodological limitations. AUTHORS' CONCLUSIONS: Based on
      the currently available evidence, myeloablative therapy seems to work in terms of
      event-free survival. For overall survival there is currently no evidence of
      effect when additional follow-up data are included. No definitive conclusions can
      be made regarding adverse effects and quality of life, although possible higher
      levels of adverse effects should be kept in mind. A definitive conclusion
      regarding the effect of myeloablative therapy in different subgroups is not
      possible. This systematic review only allows a conclusion on the concept of
      myeloablative therapy; no conclusions can be made regarding the best treatment
      strategy. Future trials on the use of myeloablative therapy for high-risk
      neuroblastoma should focus on identifying the most optimal induction and/or
      myeloablative regimen. The best study design to answer these questions is a RCT.
      These RCTs should be performed in homogeneous study populations (e.g. stage of
      disease and patient age) and have a long-term follow-up. Different risk groups,
      using the most recent definitions, should be taken into account.It should be kept
      in mind that recently the age cut-off for high risk disease was changed from one
      year to 18 months. As a result it is possible that patients with what is now
      classified as intermediate-risk disease have been included in the high-risk
      groups. Consequently the relevance of the results of these studies to the current
      practice can be questioned. Survival rates may be overestimated due to the
      inclusion of patients with intermediate-risk disease.

PMID- 23970446
TI  - Thermally induced process-related contaminants: the example of acrolein and the
      comparison with acrylamide: opinion of the Senate Commission on Food Safety
      (SKLM) of the German Research Foundation (DFG).
AB  - alpha,beta-Unsaturated aliphatic carbonyl compounds are naturally widespread in
      food, but are also formed during the thermal treatment of food. This applies, for
      example, to the genotoxic carcinogen acrylamide (AA), but also to acrolein (AC),
      the simplest alpha,beta-unsaturated aldehyde. First observations indicate that
      human exposure to AC may be higher than the exposure to AA. The DFG Senate
      Commission on Food Safety therefore compared data on AC and AA available in the
      scientific literature, evaluating current knowledge on formation, occurrence,
      exposure, metabolism, biological effects, toxicity, and carcinogenicity and
      defined knowledge gaps as well as research needs in an opinion on November 19,
      2012, in German. The English version was agreed on April 17, 2013. 

PMID- 23970445
TI  - Low-level laser (light) therapy (LLLT) for treatment of hair loss.
AB  - OBJECTIVE: Alopecia is a common disorder affecting more than half of the
      population worldwide. Androgenetic alopecia, the most common type, affects 50% of
      males over the age of 40 and 75% of females over 65. Only two drugs have been
      approved so far (minoxidil and finasteride) and hair transplant is the other
      treatment alternative. This review surveys the evidence for low-level laser
      therapy (LLLT) applied to the scalp as a treatment for hair loss and discusses
      possible mechanisms of actions. METHODS AND MATERIALS: Searches of PubMed and
      Google Scholar were carried out using keywords alopecia, hair loss, LLLT,
      photobiomodulation. RESULTS: Studies have shown that LLLT stimulated hair growth
      in mice subjected to chemotherapy-induced alopecia and also in alopecia areata.
      Controlled clinical trials demonstrated that LLLT stimulated hair growth in both
      men and women. Among various mechanisms, the main mechanism is hypothesized to be
      stimulation of epidermal stem cells in the hair follicle bulge and shifting the
      follicles into anagen phase. CONCLUSION: LLLT for hair growth in both men and
      women appears to be both safe and effective. The optimum wavelength, coherence
      and dosimetric parameters remain to be determined.

PMID- 23970447
TI  - Chunggan extract (CGX), methionine-and choline-deficient (MCD) diet-induced
      hepatosteatosis and oxidative stress in C57BL/6 mice.
AB  - In the present study, we aimed to evaluate the hepatoprotective and antioxidant
      effects of Chunggan extract (CGX) in an animal model of hepatosteatosis. The
      C57BL/6N mice were fed either methionine- and choline-sufficient (MCS) diet (n =
      10) or a methionine- and choline-deficient (MCD) diet (n = 50) for 4 weeks, and
      then they were treated orally with CGX (100 or 200 mg/kg), ursodeoxycholic acid
      (80 mg/kg, as a positive control), or distilled water (DW, MCS diet group, and
      MCD diet group) for the final 2 weeks (once per day). The MCD diet induced severe
      hepatic injury with the typical features of hepatosteatosis in both serum and
      hepatic tissues. CGX treatment significantly attenuated these alterations in the
      serum levels including triglyceride (TG), aspartate aminotransferase, alanine
      aminotransferase, alkaline phosphatase, and total bilirubin. Moreover, CGX also
      efficiently prevented from the hepatic TG accumulation in the hepatic tissue,
      evidenced by histopathological findings, compared with the MCD diet. In addition,
      CGX treatment significantly ameliorated the excessive oxidative stress and
      antioxidant markers in the serum as well as the hepatic levels of reactive oxygen
      species, the levels of malondialdehyde, the protein carbonyl, and total
      antioxidant capacity, and the activities of superoxide dismutase, catalase,
      glutathione peroxidase, and glutathione reductase. In conclusion, our results
      indicate the experimental relevance of CGX for potential clinical application in
      patients with hepatosteatotic disorders and a possible mechanism related to its
      antioxidant properties.

PMID- 23970449
TI  - How common are varicocoeles? New data on the prevalence in adolescence and new
      discussions.

PMID- 23970448
TI  - Flavonoid glycosides from the stem bark of Margaritaria discoidea demonstrate
      antibacterial and free radical scavenging activities.
AB  - One new flavonoid glycoside, along with three known flavonoid glycosides were
      isolated from the stem bark of Margaritaria discoidea, which is traditionally
      used in the management of wounds and skin infections in Ghana. The new flavonoid
      glycoside was elucidated as hydroxygenkwanin-8-C-[alpha-rhamnopyranosyl-(1 -> 6)]
      beta-glucopyranoside (1) on the basis of spectroscopic analysis. The isolated
      compounds demonstrated free-radical scavenging as well as some level of
      antibacterial activities. Microorganisms including Staphylococcus aureus are
      implicated in inhibiting or delaying wound healing. Therefore, any agent capable
      of reducing or eliminating the microbial load present in a wound as well as
      decreasing the levels of reactive oxygen species may facilitate the healing
      process. These findings therefore provide some support to the
      ethnopharmacological usage of the plant in the management of wounds.

PMID- 23970450
TI  - Varicocoele among 1 300 000 Israeli adolescent males: time trends and association
      with body mass index.
AB  - Scarce data are available on epidemiology of varicocoele, the most common
      surgically correctable cause of male infertility. The objectives of this study
      were to evaluate the association between body mass index (BMI) and varicocoele
      and to assess trends in prevalence over time. We conducted a nationwide
      population-based long-term (1967-2010) study among 1 323 061 Israeli adolescent
      males using data from mandatory medical examination. BMI was grouped into
      underweight, normal weight, overweight and obese categories by percentiles
      adjusted for age in months and by further classification to five categories
      within normal weight. Univariable and multivariable logistic regression models
      were constructed, adjusting for possible confounders. Varicocoele prevalence (N =
      47 398) increased during the study period from 1.6% for the 1950-1954 birth
      cohort to 4.6% for the 1990-1993 birth cohort, with the steepest rise in the
      normal weight group. Varicocoele unadjusted rates were highest (4.1%) among
      underweight and lowest (1.6%) among obese. In a multivariable model, adjusted for
      birth cohort, height, age and socio-demographic factors, we found a decreased
      risk for varicocoele in the overweight group [odds ratio (OR) = 0.51, 95%
      confidence interval (CI): 0.49, 0.54] and the obese group (OR = 0.34, 95% CI:
      0.32, 0.37), compared with the normal weight group. Within the normal weight
      group, a monotonic inverse association between BMI percentile and varicocoele was
      observed, most notable among 75-84.9 percentile compared to 25-49.9 percentile
      (OR = 0.65, 95% CI: 0.63, 0.68). In conclusion, varicocoele is common among
      adolescents in Israel, and its prevalence had increased in recent decades,
      providing clues to direct further andrological research on the role of modern
      lifestyle and environment in the aetiology of varicocoele. BMI, across
      percentiles, was found to be monotonically inversely associated with varicocoele,
      thus directing research and clinical efforts. 

PMID- 23970451
TI  - Analysis of DNA damage after human sperm cryopreservation in genes crucial for
      fertilization and early embryo development.
AB  - Sperm cryopreservation is widely used in clinic for insemination, in vitro
      fertilization and other procedures such as intracytoplasmic sperm injection. The
      assessment after freezing/thawing of spermatozoa viability, motility and
      sometimes DNA integrity (mainly using fragmentation assays) has been considered
      enough to guarantee the safety and effectiveness of the technique. However, it is
      known that, even when fragmentation is absent, a significant DNA damage could be
      detected in some genome regions. This is particularly important considering that,
      during the last years, several studies have pointed out the importance of key
      paternal genes in early embryo development. In this study, using normozoospermic
      donors, we present a candidate gene approach in which we quantify the number of
      lesions produced by freezing/thawing over key genes (PRM1, BIK, FSHB, PEG1/MEST,
      ADD1, ARNT, UBE3A, SNORD116/PWSAS) using quantitative PCR. Our results
      demonstrated that the cryopreservation protocol used, which is routinely employed
      in clinic, produced DNA lesions. The genes studied are differentially affected by
      the process, and genome regions related to Prader-Willi and Angelman syndromes
      were among the most damaged: SNORD116/PWSAS (4.56 +/- 1.84 lesions/10 kb) and
      UBE3A (2.22 +/- 1.3 lesions/10 kb). To check if vitrification protocols could
      reduce these lesions, another experiment was carried out studying some of those
      genes with higher differences in the first study (FSHB, ADD1, ARNT and
      SNORD116/PWSAS). The number of lesions was not significantly reduced compared to
      cryopreservation. These results could be relevant for the selection of the most
      adequate available cryopreservation protocol in terms of the number of lesions
      that produced over key genes, when no differences with other traditional
      techniques for DNA assessment could be detected. 

PMID- 23970452
TI  - DNA methylation in spermatozoa as a prospective marker in andrology.
AB  - Recent studies have shown associations of aberrant DNA methylation in spermatozoa
      with idiopathic infertility. The analysis of DNA methylation of specific genes
      could therefore serve as a valuable diagnostic marker in clinical andrology. For
      this purpose, rapid and reliable detection methods, reference values and the
      temporal stability of spermatozoal DNA methylation need to be established and
      demonstrated. In this prospective study, swim-up purified semen samples from 212
      consecutive patients (single samples), 31 normozoospermic volunteers (single
      samples) and 10 normozoospermic volunteers (four samples at days 1, 3, 42 and 45
      plus a fifth sample after 180-951 days) were collected. Spermatozoal DNA was
      isolated, bisulphite converted and DNA methylation was analysed by
      pyrosequencing. DNA methylation of the maternally imprinted gene MEST was
      measured in samples of 212 patients and 31 normozoospermic volunteers and the
      temporal stability of eight different genes and two repetitive elements was
      examined in consecutive samples of 10 normozoospermic volunteers. MEST DNA
      methylation was significantly associated with oligozoospermia, decreased bi
      testicular volume and increased FSH levels. A reference range for spermatozoal
      MEST DNA methylation (0-15%) was established using the 95th percentile of DNA
      methylation in normozoospermic volunteers. Using this reference range, around 23%
      of our patient cohort displayed an aberrant MEST DNA methylation. This epigenetic
      aberration was found to be significantly associated with bi-testicular volume,
      sperm concentration and total sperm count. DNA methylation in normozoospermic
      volunteers was stable over a time period of up to 951 days in contrast to
      classical semen parameters. Our data show that MEST DNA methylation fulfils the
      prerequisites to be used as routine parameter and support its use during
      andrological workup if a prognostic value can be shown in future. 

PMID- 23970453
TI  - Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric
      therapy for idiopathic male infertility: a meta-analysis.
AB  - The aim of this study was to synthesize and present the latest available evidence
      regarding the use of oestrogen antagonists as empiric medical therapy for
      idiopathic male infertility with oligo and/or asthenoteratozoospermia through
      meta-analysis of randomized controlled trials (RCTs). Systematic literature
      acquisition was done for English and other foreign language biomedical databases
      up to March, 2013. RCTs relevant to the topic were identified and critically
      appraised independently by two physician reviewers. Dichotomous data of pregnancy
      rate and adverse events were extracted for calculation of odds ratio (OR) and 95%
      confidence interval (CI). Effect estimates were pooled using Peto method with
      fixed effect model. The continuous data of semen and endocrine parameters were
      calculated for the mean difference between pre- and post-treatment effects, the
      weighted mean difference (WMD) and SD between the control and intervention group
      were determined and pooled using the random effects model. Inter-study
      heterogeneity and publication bias were assessed. The Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses guideline for meta-analysis reporting
      was followed. Eleven RCTs of good methodological quality were included for meta
      analysis. The pooled effect estimates showed that oestrogen antagonists use was
      associated with a statistically significant increased pregnancy rate compared
      with controls (pooled OR 2.42; 95% CI 1.47-3.94; p = 0.0004). Significant
      increase in sperm concentration (WMD 5.24; 95% CI 2.12, 88.37; p = 0.001) and per
      cent sperm motility (WMD 4.55; 95% CI 0.73, 8.37; p = 0.03) were also noted.
      While significant elevation of serum follicle stimulating hormone (WMD 4.19 95%
      CI 2.05, 6.34; p = 0.0001) and testosterone (WMD 54.59; 95% CI 15.92, 93.27; p =
      0.006) was associated with its use. No significant difference in adverse event
      was noted between oestrogen antagonists-treated group and controls. The evidence
      suggests that oestrogen antagonists as empiric medical therapy for idiopathic
      male infertility with low non-serious adverse event associated, may increase
      spontaneous pregnancy rate, improve sperm concentration and per cent sperm
      motility. 

PMID- 23970454
TI  - Clinical implications of measuring prolactin levels in males of infertile
      couples.
AB  - Although in females of infertile couples abnormal prolactin (PRL) has a
      definitive role in the medical flowchart, its role in males is less clear. Animal
      models suggest that PRL does not play a major role in male reproduction, although
      its trophic action on male accessory glands was often observed. Studies in humans
      are scanty. We systematically evaluated possible clinical and ultrasound
      correlates of PRL in males of infertile couples. Of 288 consecutive males of
      infertile couples, 269 (36.6 +/- 4.4 years) without genetic abnormalities were
      studied. All men underwent physical, biochemical, seminal evaluation and scrotal
      and transrectal ultrasound before and after ejaculation. Ejaculatory and erectile
      functions were assessed by Premature Ejaculation Diagnostic Tool (PEDT) and
      International Index of Erectile Function (IIEF)-15 respectively; prostate-related
      symptoms by National Institutes of Health-Chronic Prostatitis Symptom Index and
      International Prostate Symptom Score; psychological symptoms by Middlesex
      Hospital Questionnaire. Among semen parameters, only the positive association
      between PRL and ejaculate volume was significant, even adjusting for age, total
      testosterone and thyroid-stimulating hormone (adj. r = 0.126, p < 0.05). In a
      logistic ordinal model, adjusting for the aforementioned confounders and
      ejaculate volume, PRL was negatively associated with delaying ejaculation
      according to PEDT#1 score (Wald = 4.65, p < 0.05). In an age- and ejaculate
      volume-adjusted, iterative binary logistic model, low PRL was associated with a
      fivefold risk of any failure in controlling ejaculation (HR = 5.15 [1.15-23], p <
      0.05). Among scrotal and transrectal ultrasound features, we found a significant
      positive association between PRL and seminal vesicles (SV) volume and
      inhomogeneity, before and after ejaculation, and with deferential ampullas
      diameter. Associations with PRL were confirmed in nested 1 : 1 case-control
      analysis. No significant associations were found between PRL and other clinical
      parameters. For the first time, this study extends the concept of a trophic
      effect of PRL on male accessory glands from animals to humans. We report a
      positive association among PRL and ejaculate and SV volume, before and after
      ejaculation. Low PRL is associated with a lessened ability to control
      ejaculation. 

PMID- 23970455
TI  - Clinical characteristics and penile afferent neuronal function in patients with
      primary delayed ejaculation.
AB  - Primary delayed ejaculation (DE) is a relatively uncommon condition and has not
      been studied broadly. In this study, we aimed to investigate the clinical
      characteristics and penile afferent neuronal function using somatosensory evoked
      potentials in patients with primary DE. Twenty-four patients with primary DE and
      24 age-matched normally potent men were enrolled in this study. Results indicated
      that patients with primary DE had remarkably higher frequency of masturbatory
      activity (especially, some with idiosyncratic styles), lower night emissions,
      longer intravaginal ejaculation latency time (IELT), higher anxiety and
      depression states (p = 0.010, p = 0.017, p < 0.001, p < 0.001, p < 0.001
      respectively). In addition, the mean penile shaft sensory threshold values in the
      patients were considerably higher than those in the healthy men (p < 0.001). Mean
      latencies of dorsal nerve somatosensory evoked potential DNSEP were 4.32 ms
      longer in the DE group than those in the control group (p < 0.001). However, the
      latencies of glans penis somatosensory evoked potential (GPSEP) between the two
      group showed no significant difference (p = 0.985). At the same time, in
      comparison with the control group, the amplitudes of DNSEP were considerably
      lower in the DE group (p = 0.016), but not in the amplitudes of GPSEP (p =
      0.934). This study indicates that the patients with primary DE appear to have
      penile shaft rather than glans hyposensitivity and hypoexcitability, and
      adaptation to a certain masturbatory technique (higher and idiosyncratic) may be
      related to the causes of primary DE, which is also associated with lower night
      emissions, longer IELT, higher anxiety and depression states. 

PMID- 23970456
TI  - Increased subsequent risk of erectile dysfunction in patients with irritable
      bowel syndrome: a nationwide population-based cohort study.
AB  - This retrospective population-based study aimed to investigate associations
      between erectile dysfunction (ED) and the irritable bowel syndrome (IBS) using a
      Taiwanese cohort. We identified 17 608 male patients who were newly diagnosed
      with IBS from 1997 to 2010. The date that the diagnosis of IBS had been made was
      the index date. IBS patients with a history of ED before the index date or with
      incomplete demographic information were excluded. 70 432 age-matched subjects
      without IBS were selected as comparison cohort. Both cohorts were followed until
      the end of 2010 or censored. Cox proportional hazard regression model was used to
      estimate the effects of IBS on ED risks. The incidence rate ratio of ED in the
      IBS cohort was 2.92 times higher than that in the non-IBS cohort (29.5 vs. 10.1
      per 10 000 person-years), with an adjusted hazard ratio (aHR) of 2.58 (95%
      confidence interval [CI]: 2.24-2.98). The risk of ED increased with increasing
      age and number of comorbidities. Patients with depression were at a higher risk
      of ED (aHR: 1.97; 95% CI: 1.49-2.63) compared with the subjects without
      depression. IBS patients had a higher risk of developing ED compared with non-IBS
      subjects. Ageing and comorbidities including diabetes, cardiovascular disease,
      chronic kidney disease and depression were associated with the risk of ED. 

PMID- 23970457
TI  - Assisted reproductive technology: an overview of Cochrane Reviews.
AB  - BACKGROUND: As many as one in six couples will encounter problems with fertility,
      defined as failure to achieve a clinical pregnancy after regular intercourse for
      12 months. Increasingly, couples are turning to assisted reproductive technology
      (ART) for help with conceiving and ultimately giving birth to a healthy live baby
      of their own. Fertility treatments are complex, and each ART cycle consists of
      several steps. If one of the steps is incorrectly applied, the stakes are high as
      conception may not occur. With this in mind, it is important that each step of
      the ART cycle is supported by good evidence from well-designed studies.
      OBJECTIVES: To summarise the evidence from Cochrane systematic reviews on
      procedures and treatment options available to couples with subfertility
      undergoing assisted reproductive technology (ART). METHODS: Published Cochrane
      systematic reviews of couples undergoing ART (in vitro fertilisation or
      intracytoplasmic sperm injection) were eligible for inclusion in the overview. We
      also identified Cochrane reviews in preparation, for future inclusion.The
      outcomes of the overview were live birth (primary outcome), clinical pregnancy,
      multiple pregnancy, miscarriage and ovarian hyperstimulation syndrome (secondary
      outcomes). Studies of intrauterine insemination and ovulation induction were
      excluded.Selection of systematic reviews, data extraction and quality assessment
      were undertaken in duplicate. Review quality was assessed by using the AMSTAR
      tool. Reviews were organised by their relevance to specific stages in the ART
      cycle. Their findings were summarised in the text and data for each outcome were
      reported in 'Additional tables'. MAIN RESULTS: Fifty-four systematic reviews
      published in The Cochrane Library were included. All were high quality. Thirty
      reviews identified interventions that were effective (n = 18) or promising (n =
      12), 13 reviews identified interventions that were either ineffective (n = 3) or
      possibly ineffective (n=10), and 11 reviews were unable to draw conclusions due
      to lack of evidence.An additional 15 protocols and two titles were identified for
      future inclusion in this overview. AUTHORS' CONCLUSIONS: This overview provides
      the most up to date evidence on ART cycles from systematic reviews of randomised
      controlled trials. Fertility treatments are costly and the stakes are high. Using
      the best available evidence to optimise outcomes is best practice. The evidence
      from this overview could be used to develop clinical practice guidelines and
      protocols for use in daily clinical practice, in order to improve live birth
      rates and reduce rates of multiple pregnancy, cycle cancellation and ovarian
      hyperstimulation syndrome.

PMID- 23970458
TI  - Gonadotrophins for idiopathic male factor subfertility.
AB  - BACKGROUND: Male factors leading to subfertility account for at least half of all
      cases of subfertility worldwide. Although some causes of male subfertility are
      treatable, treatment of idiopathic male factor subfertility remains empirical.
      Researchers have used gonadotrophins to improve sperm parameters in idiopathic
      male factor subfertility with the ultimate goal of increasing birth and pregnancy
      rates, but results have been conflicting. OBJECTIVES: To determine the effect of
      systemic follicle-stimulating hormone (FSH) on live birth and pregnancy rates
      when administered to men with idiopathic male factor subfertility . SEARCH
      METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group
      Specialised Register (14 January 2013), the Cochrane Central Register of
      Controlled Trials (CENTRAL; The Cochrane Library, Issue 12 of 12, 2012), Ovid
      MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid
      MEDLINE (1946 to 14 January 2013), Ovid EMBASE (1980 to week 2 of 2013), Ovid
      PsycINFO (1806 to week 2 of 2013), trial registers for ongoing and registered
      trials at ClinicalTrials.gov (19 January 2013), the World Health Organisation
      International Trials Registry Platform (19 January 2013), The Cochrane Library
      Database of Abstracts of Reviews of Effects (19 January 2013) and OpenGrey for
      grey literature from Europe (19 January 2013). Searches were not limited by
      language. Bibliographies of included and excluded trials and abstracts of major
      meetings were searched for additional trials. SELECTION CRITERIA: Randomised
      controlled trials (RCTs) in which gonadotrophins were compared with placebo or no
      treatment for participants with idiopathic male factor subfertility. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected the trials,
      assessed risk of bias and extracted data on live birth, pregnancy and adverse
      effects. We included data on pregnancies that occurred during or after
      gonadotrophin therapy. Study authors and pharmaceutical companies were asked to
      provide missing and unpublished data and/or additional information. MAIN RESULTS:
      Six RCTs with 456 participants and variable treatment and follow-up periods were
      included. From the limited data, the live birth rate per couple randomly assigned
      (27% vs 0%; Peto odds ratio (OR) 9.31, 95% confidence interval (CI) 1.17 to
      73.75, one study, 30 participants, very low-quality evidence) and the spontaneous
      pregnancy rate per couple randomly assigned (16% vs 7%; Peto OR 4.94, 95% CI 2.13
      to 11.44, five studies, 412 participants, I(2) = 0%, moderate-quality evidence)
      were significantly higher in men receiving gonadotrophin treatment than in men
      receiving placebo or no treatment. No significant difference between groups was
      noted when intracytoplasmic sperm injection (ICSI) or intrauterine insemination
      (IUI) was performed. None of the included studies reported miscarriage rates, and
      adverse events data were sparse. AUTHORS' CONCLUSIONS: Encouraging preliminary
      data suggest a beneficial effect on live birth and pregnancy of gonadotrophin
      treatment for men with idiopathic male factor subfertility, but because the
      numbers of trials and participants are small, evidence is insufficient to allow
      final conclusions. Large multi-centre trials with adequate numbers of
      participants are needed.

PMID- 23970459
TI  - Reliability and validity of the quality of life-Alzheimer disease Chinese
      version.
AB  - OBJECTIVES: To evaluate the psychometric properties of the quality of life
      Alzheimer disease (QOL-AD) Chinese version in patients with dementia in mainland,
      China and to compare patient and caregiver reports of patient QOL. METHODS: The
      QOL-AD Chinese version was established following standard guidelines for cross
      cultural adaptation of measures. The reliability was assessed by internal
      consistency and test-retest reliability. The validity included construct and
      convergent validity. A paired Student t test was performed to determine
      differences between patient reports and caregiver reports. RESULTS: The
      reliability for both patient and caregiver reports on the QOL-AD was good
      (Cronbach alpha values of 0.66 and 0.87; intraclass correlation coefficients of
      0.84 and 0.90 for patient and caregiver reports, respectively). The validity of
      patient and caregiver reports was supported by correlation with domain measures.
      All of the multitrait-multimethod correlations demonstrated a high relationship
      between patient reports and caregiver reports, ranging from 0.26 to 0.55. The
      caregivers rated patient QOL significantly higher than did the patients.
      CONCLUSION: The findings support the use of the Chinese version of the QOL-AD as
      a generic instrument to measure QOL of AD in mainland China. Further research is
      needed to clarify the relationship between patient and caregiver reports of
      patient QOL.

PMID- 23970460
TI  - Apathy in elderly nondemented patients with Parkinson's disease: clinical
      determinants and relationship to quality of life.
AB  - OBJECTIVES: To describe the prevalence and clinical determinants of apathy in
      elderly nondemented patients with Parkinson's disease (PD) and their relationship
      to quality of life (QoL). METHODS: A total of 106 nondemented elderly patients
      with PD were examined using the Movement Disorder Society-Unified Parkinson's
      Disease Rating Scale (MDS-UPDRS), Starkstein Apathy Scale, Hospital Anxiety and
      Depression Scale, Beck Depression Inventory-II, and 39-item Parkinson's disease
      quality of life questionnaire. RESULTS: Apathy was present in 54% of the studied
      population. Factors associated with apathy were higher depression scores and a
      lower daily levodopa equivalent dose. Longer disease duration, higher motor MDS
      UPDRS subscore, and higher depression and anxiety scores, but not apathy, were
      found to be associated with worse QoL. CONCLUSIONS: Although apathy does not seem
      to be an independent predictor of worse QoL specifically in elderly patients with
      PD, it remains very relevant, as its presence increases caregiver burden. Both
      depression and potential dopaminergic treatment underdosing can be properly
      managed, thus potentially reducing the prevalence and severity of apathy in a
      proportion of the apathetic patients with PD.

PMID- 23970461
TI  - Soft nanostructured films with an ultra-low volume fraction of percolating hard
      phase.
AB  - In this study, aqueous emulsion polymerization of n-butyl acrylate is performed
      in batch conditions without surfactants using a poly(acrylic acid)
      trithiocarbonate macro-RAFT agent to control the polymerization and to stabilize
      the emulsion. According to the polymerization-induced self-assembly (PISA)
      approach, well-defined amphiphilic PAA-b-PBA diblock copolymers form and self
      assemble during synthesis to yield highly stable core-shell particles with an
      extremely thin hard PAA shell. For the first time, we report here the specific
      properties of films obtained from these particular latexes. After drying the
      aqueous dispersion, tough and transparent films are obtained. Although the films
      are not chemically cross-linked, they do not dissolve in good solvents for PBA.
      Moreover, they remain transparent even after immersion in water. Rheology shows
      that the films are both stiff and ductile, thanks to the nanostructured but very
      low volume fraction (less than 3 wt%) of PAA forming a percolating network in the
      soft PBA. Compared with conventional core-shell-based films, this approach
      affords for the first time a route to a thin percolating honeycomb nanostructure
      with a sharp and strong interface between the two phases. The versatility of the
      synthetic procedure opens perspectives for a large range of functional materials.

PMID- 23970462
TI  - Chemotherapy for thymic carcinoma and advanced thymoma in adults.
AB  - BACKGROUND: Thymic carcinoma or advanced thymoma is a rare cancer of the thymus
      gland that tends to be aggressive and infiltrate neighbouring organs, making
      total resection very difficult. Induction or adjuvant chemotherapy, or both, are
      often used in a multimodality approach to treat people affected by this
      condition, but the effectiveness of chemotherapy for thymic carcinoma or advanced
      thymoma remains uncertain. OBJECTIVES: To assess the role of chemotherapy in
      adults with thymic carcinoma or advanced thymoma. SEARCH METHODS: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 7), MEDLINE
      (accessed via Ovid from 1966 to July 2012), EMBASE (accessed via Ovid, from 1980
      to July 2012), Latin American and Caribbean Literature on Health Sciences
      (LILACS), the Chinese Biological Medicine Database (CBM, 1978 to July 2012),
      China National Knowledge Infrastructure (CNKI, 1980 to July 2012) and the Chinese
      scientific periodical database VIP Information (VIP, 1989 to July 2012). There
      was no language restriction in searching for studies. SELECTION CRITERIA: We
      planned to include randomised controlled trials (RCTs) of  trials using
      chemotherapy (either single-agent or combination chemotherapy plus surgery,
      radiotherapy or not) for thymic carcinoma and/or advanced thymoma. We planned to
      include all adults (aged 18 years and over) diagnosed with thymic carcinoma
      and/or with Masaoka stage III or IV thymic tumours. The intended primary outcomes
      were overall survival (OS) and progression-free survival (PFS). DATA COLLECTION
      AND ANALYSIS: Two review authors independently evaluated the search results
      according to the inclusion and exclusion criteria. There were no studies
      identified for inclusion and therefore no data extraction was completed. MAIN
      RESULTS: No RCTs were eligible for inclusion in this review. We report details of
      excluded prospective studies in an additional table and try to provide some
      useful evidence regarding current practice. AUTHORS' CONCLUSIONS: There were no
      RCTs eligible for inclusion in this review. In current practice the most common
      regimen for adult patients with thymic carcinoma or advanced thymoma is cisplatin
      based chemotherapy. Considering the condition is rare, it is suggested that an
      international group is set up to organise and evaluate prospective collection of
      data from cohorts of patients to inform current clinical practice.

PMID- 23970463
TI  - Clinical and immunological correlates of chest X-ray abnormalities in HIV
      infected South African children with limited access to anti-retroviral therapy.
AB  - BACKGROUND: The chest X-ray (CXR) abnormalities of human immunodeficiency virus
      (HIV)-infected children in low/middle income countries (LMIC's) have not been
      well studied. OBJECTIVE: To describe the CXR abnormalities and associated
      clinical/immunological features in HIV-infected South African children. MATERIALS
      AND METHODS: A prospective study of HIV-infected children who underwent baseline
      chest radiography and clinical and immunological HIV-staging. CXR abnormalities
      were stratified as grade 1 (mild) or grade 2 (moderate/severe). Univariate and
      multiple logistic regression analyses assessed associations between radiological
      severity and clinical/immunological parameters. RESULTS: Three hundred thirty
      children (53% male), median age 23.8 months, were included; 303 (92%) had
      moderate/severe clinical disease and 225 (68%) moderate/severe immune
      suppression; 52 (16%) had a normal CXR; 169 (51%) had grade 2 CXR abnormalities,
      manifesting as: confluent opacification (n = 91, 28%), nodules (n = 37, 11%), or
      nodules with opacification (n = 41, 12%) Grade 2 abnormality was associated with
      more advanced clinical HIV disease (OR: 6.9; 95% CI: 1.9-25.6), CD4+ less than
      20% (OR: 1.8; 95% CI: 1.0-3.0) and age over 24 months (OR: 4.1; 95% CI: 2.1-8.0).
      CONCLUSION: CXR abnormalities are common in HIV-infected children in LMIC's. The
      extent of radiological abnormality correlates with age and clinical and
      immunological severity of HIV-disease.

PMID- 23970464
TI  - Bridging phenomenon - Simplifying complex ear reconstructions.
AB  - BACKGROUND: Extirpation of noninvasive skin tumors of the anterior ear may create
      large defects. Various flaps, described to cover these defects, demand special
      knowledge without which a loss of the fine detail of the ear may result. METHODS:
      Healthy, exposed cartilage is deliberately excised leaving a basic framework for
      support, thus preserving contours and a well-vascularized recipient bed for full
      thickness skin grafting. The grafts heal by revascularization and "bridging," a
      phenomenon whereby grafts on avascular beds (such as denuded cartilage) are
      revascularized. RESULTS: By marrying clinical experience gained during microtia
      reconstruction with insights regarding the bridging phenomenon derived from the
      laboratory, our 17 reconstructed ears healed without serious complications and
      kept their normal contours and shape, and there was no recurrence of the
      carcinoma. CONCLUSION: Satisfactory patient-centered outcome can be obtained in
      reconstructing defects of one-third to two-thirds of the total anterior surface
      of the ear relying on the bridging phenomenon.

PMID- 23970465
TI  - Molecularly imprinted SPE coupled with HPLC for the selective separation and
      enrichment of alkyl imidazolium ionic liquids in environmental water samples.
AB  - A novel 1-butyl-3-methylimidazolium chloride ionic liquid surface imprinted solid
      phase sorbent was synthesized. The as-prepared material was characterized by SEM,
      Brunauer-Emmett-Teller surface area analysis and Fourier Transform IR
      measurements. Then its adsorption properties for alkyl imidazolium ionic liquids,
      including adsorption capacities, adsorption kinetics, and properties of selective
      separation and enrichment were studied in detail. It was shown that the ionic
      liquid surface imprinted polymer exhibited high selective recognition
      characteristics for the imidazolium chloride ionic liquids with short alkyl
      chains (C(n)mimCl, n = 2, 4, 6, 8) and the adsorption equilibrium was achieved
      within 25 min. Various parameters were optimized for the 1-butyl-3
      methylimidazolium chloride ionic liquid surface imprinted polymer SPE column,
      such as flow rate, eluent solvent, selectivity, and reusability of the column.
      Then, the SPE column coupled with HPLC was used for the determination of alkyl
      imidazolium ionic liquids. Experimental results showed that the existence of
      their structural analogs and common concomitants in environmental matrices did
      not affect the enrichment of 1-butyl-3-methyl imidazolium chloride ionic liquid.
      The average recoveries of 1-butyl-3-methylimidazolium chloride ionic liquid in
      spiked water samples were in the range of 92.0-102.0% with the RSD lower than
      5.8%.

PMID- 23970466
TI  - Optimization of ceragenins for prevention of bacterial colonization of hydrogel
      contact lenses.
AB  - PURPOSE: We provided contact lens hydrogels with an antibacterial innate immune
      function using nonpeptide mimics of endogenous antimicrobial peptides. METHODS:
      Antimicrobial peptide mimics, ceragenins, were prepared for either covalent
      attachment to hydrogels or for controlled elution from lenses. The lipophilicity
      of the ceragenins was varied incrementally to provide differing levels of
      association with hydrophobic domains in lenses. Ceragenin-containing lenses were
      challenged repeatedly with Staphylococcus aureus or Pseudomonas aeruginosa in
      nutrient media. Bacterial growth and biofilm formation on lenses were quantified.
      RESULTS: A ceragenin covalently fixed in lenses effectively inhibited S. aureus
      biofilm formation on lenses in 10% tryptic soy broth (approximately 3-log
      reduction), but did not reduce biofilm formation in 100% tryptic soy broth.
      Ceragenins designed to elute from lenses were incorporated at 1% relative to the
      dry weight of the lenses. The ceragenin with the optimal lipid content, CSA-138,
      prevented bacterial colonization of lenses for 15 days with P. aeruginosa and for
      30 days with S. aureus (daily exchange of growth media and reinoculation with 106
      CFU). Measurement of CSA-138 elution showed that concentrations of the ceragenin
      never exceeded 5 MUg/mL in a 24-hour period and that after 4 days of elution,
      concentrations dropped to <0.5 MUg/mL, while maintaining antibacterial activity.
      CONCLUSIONS: Ceragenin CSA-138 appears well suited for providing an innate immune
      like function to abiotic hydrogel contact lenses for extended periods of time.
      Elution of even low concentrations of CSA-138 (<0.5 MUg) is sufficient to
      eliminate inocula of 106 CFU of S. aureus and P. aeruginosa.

PMID- 23970467
TI  - Efficacy of osmoprotectants on prevention and treatment of murine dry eye.
AB  - PURPOSE: To evaluate the efficacy of osmoprotectants on prevention and treatment
      of dry eye in a murine model. METHODS: Dry eye was induced in mice by using an
      intelligently controlled environmental system (ICES). Osmoprotectants betaine, L
      carnitine, erythritol, or vehicle (PBS) were topically administered to eyes four
      times daily following two schedules: schedule 1 (modeling prevention): dosing
      started at the beginning of housing in ICES and lasted for 21 or 35 days;
      schedule 2 (modeling treatment): dosing started after ICES-housed mice developed
      dry eye (day 21), continuing until day 35. Treatment efficacy was evaluated for
      corneal fluorescein staining; corneal epithelial apoptosis by TUNEL and caspase-3
      assays; goblet cell numbers by PAS staining; and expression of inflammatory
      mediators, TNF-alpha, IL-17, IL-6, or IL-1beta by using RT-PCR on days 0, 14, 21,
      and/or 35. RESULTS: Compared with vehicle, prophylactic administration of
      betaine, L-carnitine, or erythritol significantly decreased corneal staining and
      expression of TNF-alpha and IL-17 on day 21 (schedule 1). Treatment of mouse dry
      eye with osmoprotectants significantly reduced corneal staining on day 35
      compared with day 21 (schedule 2). Relative to vehicle, L-carnitine treatment of
      mouse dry eye for 14 days (days 21 to 35) resulted in a significant reduction in
      corneal staining, number of TUNEL-positive cells, and expression of TNF-alpha, IL
      17, IL-6, or IL-1beta, as well as significantly increased the number of goblet
      cells. CONCLUSIONS: Topical application of betaine, L-carnitine, or erythritol
      systematically limited progression of environmentally induced dry eye. L
      carnitine can also reduce the severity of such dry-eye conditions.

PMID- 23970468
TI  - Exploration of molecular factors impairing superoxide dismutase isoforms activity
      in human senile cataractous lenses.
AB  - PURPOSE: To explore different molecular factors impairing the activities of
      superoxide dismutase (SOD) isoforms in senile cataractous lenses. METHODS: Enzyme
      activity of SOD isoforms, levels of their corresponding cofactors copper (Cu),
      manganese (Mn), zinc (Zn), and expression of mRNA transcripts and proteins were
      determined in the lenses of human subjects with and without cataract. DNA from
      lens epithelium (LE) and peripheral blood was isolated. Polymerase chain reaction
      single strand conformation polymorphism (PCR-SSCP) followed by sequencing was
      carried out to screen somatic mutations. The impact of intronic
      insertion/deletion (INDEL) variations on the splicing process and on the
      resultant transcript was evaluated. Genotyping of IVS4+42delG polymorphism of
      SOD1 gene was done by PCR-restriction fragment length polymorphism (RFLP).
      RESULTS: A significant decrease in Cu/Zn- and Mn-SOD activity (P < 0.001) and in
      Cu/Zn-SOD transcript (P < 0.001) and its protein (P < 0.05) were found in
      cataractous lenses. No significant change in the level of copper (P = 0.36) and
      an increase in the level of manganese (P = 0.01) and zinc (P = 0.02) were
      observed in cataractous lenses. A significant positive correlation between the
      level of Cu/Zn-SOD activity and the levels of Cu (P = 0.003) and Zn (P = 0.005)
      was found in the cataractous lenses. DNA sequencing revealed three intronic INDEL
      variations in exon4 of SOD1 gene. Splice-junction analysis showed the potential
      of IVS4+42delG in creating a new cryptic acceptor site. If it is involved in
      alternate splicing, it could result in generation of SOD1 mRNA transcripts
      lacking exon4 region. Transcript analysis revealed the presence of complete SOD1
      mRNA transcripts. Genotyping revealed the presence of IVS4+42delG polymorphism in
      all subjects. CONCLUSIONS: The decrease in the activity of SOD1 isoform in
      cataractous lenses was associated with the decreased level of mRNA transcripts
      and their protein expression and was not associated with either modulation in the
      level of enzyme cofactors or with INDEL variations.

PMID- 23970469
TI  - Serum eyedrops antagonize the anti(lymph)angiogenic effects of bevacizumab in
      vitro and in vivo.
AB  - PURPOSE: The effect of autologous serum eyedrops on the corneal vasculature is
      undefined. Therefore, we analyzed the corneal vascular effects of serum eyedrops
      in comparison with and in combination with bevacizumab eyedrops. METHODS: In
      vitro, blood and lymphatic endothelial cells were treated with serum eyedrops,
      bevacizumab eyedrops, or a combination of both, and cell proliferation was
      measured. In vivo, inflammatory corneal neovascularization was induced by suture
      placement. Subsequently, corneal blood and lymphatic vessel progression and
      regression were analyzed after treatment with serum or bevacizumab eyedrops or a
      combination of both. Hemangiogenesis and lymphangiogenesis were quantified in
      whole mounts using CD31 and lymphatic vessel endothelial hyaluronan receptor 1
      (LYVE-1); inflammatory cell infiltration was analyzed using CD11b. Furthermore,
      corneal expression levels of interleukin 1beta, tumor necrosis factor alpha,
      vascular endothelial growth factor (VEGF) A, VEGF-C, and VEGF-D were analyzed by
      real-time PCR. RESULTS: In vitro, serum increased and bevacizumab decreased
      endothelial cell proliferation. In vivo, serum eyedrops had no significant effect
      on corneal vessel progression or regression. Bevacizumab eyedrops reduced blood
      and lymphatic vessel progression and promoted blood and lymphatic vessel
      regression. The combination of serum eyedrops and bevacizumab eyedrops attenuated
      the anti(lymph)angiogenic effects of bevacizumab. Inflammatory corneal cell
      counts were not significantly altered by serum or bevacizumab eyedrops. Serum
      eyedrops changed the proinflammatory and pro(lymph)angiogenic status of the
      cornea. Bevacizumab eyedrops significantly reduced proinflammatory and
      pro(lymph)angiogenic factor expression. Higher doses of bevacizumab did not
      restore its anti(lymph)angiogenic effects when used in combination with serum.
      CONCLUSIONS: The counteracting effects of serum eyedrops and bevacizumab eyedrops
      on the corneal vasculature should be taken into account when combined therapeutic
      regimens are considered.

PMID- 23970470
TI  - Inhibitory effect of microRNA-34a on retinal pigment epithelial cell
      proliferation and migration.
AB  - PURPOSE: Retinal pigment epithelial (RPE) cells play important roles in
      ophthalmologic diseases such as proliferative vitreoretinopathy, AMD, and
      diabetic retinopathy. MicroRNA-34a (miR-34a) has been reported to be important in
      the regulation of cell proliferation, migration, differentiation, and apoptosis.
      In this study, we explored the effects of miR-34a on RPE cells. METHODS: The
      expression level of miR-34a in subconfluent and postconfluent ARPE-19 cells was
      investigated with quantitative real-time PCR. MicroRNA mimic and small
      interfering RNA (siRNA) were transiently transfected into RPE cells. Transfected
      RPE cells were analyzed with WST-1 proliferation assay, and their migration was
      analyzed with transwell assay and in vitro scratch study. The expression or
      activation of target proteins was detected by Western blotting. RESULTS: MicroRNA
      34a was significantly downregulated in subconfluent ARPE-19 cells compared with
      postconfluent cells. Introduction of miR-34a inhibited the proliferation and
      migratory ability of RPE cells without obvious cell apoptosis. In miR-34a
      transfected cells, many important proliferation and/or migration related
      molecules such as c-Met, CDK2, CDK4, CDK6, E2F1, and phosphorylated-Cdc2 (p-Cdc2)
      were downregulated. Small interfering RNA designed to target c-Met also inhibited
      the proliferation and migration of RPE cells and downregulated CDK2, CDK6, E2F1,
      and p-Cdc2. CONCLUSIONS: MicroRNA-34a is downregulated in subconfluent RPE cells.
      MicroRNA-34a can inhibit the proliferation and migration of RPE cells through
      downregulation of its targets c-Met and other cell cycle-related molecules. Our
      results indicated that miR-34a is involved in the regulation of RPE cells.

PMID- 23970471
TI  - Age-related thinning of Bowman's layer in the human cornea in vivo.
AB  - PURPOSE: To determine the thickness of Bowman's layer (BL) in vivo in a healthy
      population and to determine its variation with age. METHODS: Eighty-two subjects
      aged 15 to 88 years with clear, healthy corneas were examined bilaterally with
      laser scanning in vivo confocal microscopy (IVCM). Bowman's layer thickness was
      determined from IVCM images of anterior and posterior BL boundaries. For a given
      eye, BL thickness was averaged across four central locations by two independent
      observers. In addition, central corneal thickness was measured by time-domain
      optical coherence tomography. RESULTS: A significant negative correlation of BL
      thickness with age was found in right eyes (Pearson r = -0.579, P < 0.0001) and
      in left eyes (r = -0.558, P < 0.0001). Linear regression analysis yielded a
      decline in BL thickness of 0.06 MUm per year. In 41 older subjects (mean age,
      64.4 years), BL thickness was significantly thinner (mean +/- SD, 8.6 +/- 1.7 MUm
      in right eyes) than that in 41 younger subjects (mean age, 31.6 years) (mean +/-
      SD, 10.7 +/- 1.6 MUm in right eyes) (P < 0.001). No correlation of corneal
      thickness with age or of BL thickness with corneal thickness was observed. Strong
      intereye correlations in BL thickness (r = 0.771, P < 0.0001) and corneal
      thickness (r = 0.969, P < 0.001) were found. CONCLUSIONS: Bowman's layer thins
      with age in the normal cornea, losing one-third of its thickness between the ages
      of 20 and 80 years. In vivo measurement of BL thickness by IVCM could aid in
      clinical assessment and planned treatments of the anterior cornea.

PMID- 23970472
TI  - A negative dielectrophoresis and gravity-driven flow-based high-throughput and
      high-efficiency cell-sorting system.
AB  - We present a negative dielectrophoresis (n-DEP)-based cell separation system for
      high-throughput and high-efficiency cell separation. To achieve a high
      throughput, the proposed system comprises macro-sized channel and cantilever-type
      electrode (CE) arrays (L * W * H = 150 um * 500 um * 50 um) to generate n-DEP
      force. For high efficiency, double separation modules, which have macro-sized
      channels and CE arrays in each separation module, are employed. In addition, flow
      regulators to precisely control the hydrodynamic force are allocated for each
      outlet. Because the hydrodynamic force and the n-DEP force acting on the target
      cell are the main determinants of the separation efficiency, we evaluate the
      theoretical amount of hydrodynamic force and n-DEP force acting on each target
      cell. Based on theoretical results, separation conditions are experimentally
      investigated. Finally, to demonstrate the separation performance, we performed
      the separation of target cells (live K562) from nontarget cells (dead K562) under
      conditions of low voltage (7Vp-p with 100 kHz) and a flow rate of 15 uL*min-1, 6
      uL*min-1, and 8 uL*min-1 in outlets 1, 2, and 3, respectively. The system can
      separate target cells with 95% separation efficiency in the case of the ratio of
      5:1 (live K562:dead K562).

PMID- 23970473
TI  - Development of a multiplexed microfluidic platform for the automated cultivation
      of embryonic stem cells.
AB  - We present a multiplexed platform for a microfabricated stem cell culture device.
      The modular platform contains all the components to control stem cell culture
      conditions in an automated fashion. It does not require an incubator during
      perfusion culture and can be mounted on the stage of an inverted fluorescence
      microscope for high-frequency imaging of stem cell cultures. A pressure-driven
      pump provides control over the medium flow rate and offers switching of the flow
      rates. Flow rates of the pump are characterized for different pressure settings,
      and a linear correlation between the applied pressure and the flow rate in the
      cell culture devices is shown. In addition, the pump operates with two culture
      medium reservoirs, thus enabling the switching of the culture medium on-the-fly
      during a cell culture experiment. Also, with our platform, the culture medium
      reservoirs are cooled to prevent medium degradation during long-term experiments.
      Media temperature is then adjusted to a higher controlled temperature before
      entering the microfabricated cell culture device. Furthermore, the temperature is
      regulated in the microfabricated culture devices themselves. Preliminary culture
      experiments are demonstrated using mouse embryonic stem cells. 

PMID- 23970474
TI  - Do psychosocial working conditions modify the effect of depressive symptoms on
      long-term sickness absence?
AB  - BACKGROUND: The objective of this study was to investigate whether work unit
      levels of psychosocial working conditions modify the effect of depressive
      symptoms on risk of long-term sickness absence (LTSA). METHODS: A total of 5,416
      Danish female eldercare workers from 309 work units were surveyed using
      questionnaires assessing depressive symptoms and psychosocial working conditions.
      LTSA was derived from a national register. We aggregated scores of psychosocial
      working conditions to the work unit-level and conducted multi-level Poisson
      regression analyses. RESULTS: Depressive symptoms, but not psychosocial working
      conditions, predicted LTSA. Psychosocial working conditions did not statistically
      significantly modify the effect of depressive symptoms on LTSA. CONCLUSIONS:
      Psychosocial working conditions did not modify the effect of depressive symptoms
      on LTSA. The results, however, need to be interpreted with caution, as we cannot
      rule out lack of exposure contrast and non-differential misclassification of the
      exposure.

PMID- 23970475
TI  - Laryngeal hibernoma: case series of a rare tumor.
AB  - BACKGROUND: Hibernomas are rare, benign tumors of brown adipose tissue uncommonly
      found in the head and neck. METHODS: A review of the English-language literature
      was conducted for this study. We present a series of 2 laryngeal hibernomas
      treated with transoral laser microsurgical resection at a tertiary referral
      center over a period of 18 years. RESULTS: Only 2 cases of laryngeal hibernoma
      have been previously described in the literature. Two additional cases were
      encountered at our institution. Preoperative imaging demonstrated a well
      circumscribed neoplasm with fat density compatible with lipoma, but internal
      heterogeneity and vascularity seen in the context of liposarcoma. Transoral laser
      microsurgical resection was successfully performed in each case. CONCLUSION:
      Despite unique radiographic features, hibernomas are difficult to distinguish
      from well-differentiated liposarcoma and lipoma variants without pathologic
      correlation. Complete surgical resection is indicated. In our experience,
      transoral laser microsurgical excision of laryngeal hibernomas is a safe,
      effective treatment modality with little associated morbidity.

PMID- 23970476
TI  - Staphylococcus aureus in early cystic fibrosis lung disease.
AB  - Staphylococcus aureus: is a common bacterial organism infecting children with
      cystic fibrosis (CF). Emerging evidence suggests early lower airway infection
      with this organism in young children with CF results in the deterioration of lung
      function, poorer nutrition parameters and heightens the airway inflammatory
      response. Despite contributing significantly to the burden of early lung disease
      among this group, there are ongoing controversies in the management of S. aureus
      infection, and gaps in our understanding of exactly how this organism causes lung
      disease. To reduce the morbidity and mortality of early infection ongoing
      research is needed to: (i) understand the early host immune response that enables
      this pathogen to reside within the CF lung; (ii) determine if there are organism
      specific factors that are associated with CF lung disease; and (iii) clarify the
      utility of anti-staphylococcal antibiotic prophylaxis and/or eradication in the
      treatment of this patient population.

PMID- 23970478
TI  - The p90 RSK family members: common functions and isoform specificity.
AB  - The p90 ribosomal S6 kinases (RSK) are implicated in various cellular processes,
      including cell proliferation, survival, migration, and invasion. In cancer, RSKs
      modulate cell transformation, tumorigenesis, and metastasis. Indeed, changes in
      the expression of RSK isoforms have been reported in several malignancies,
      including breast, prostate, and lung cancers. Four RSK isoforms have been
      identified in humans on the basis of their high degree of sequence homology.
      Although this similarity suggests some functional redundancy between these
      proteins, an increasing body of evidence supports the existence of isoform-based
      specificity among RSKs in mediating particular cellular processes. This review
      briefly presents the similarities between RSK family members before focusing on
      the specific function of each of the isoforms and their involvement in cancer
      progression.

PMID- 23970477
TI  - Novel oncogenic PDGFRA mutations in pediatric high-grade gliomas.
AB  - The outcome for children with high-grade gliomas (HGG) remains dismal, with a 2
      year survival rate of only 10% to 30%. Diffuse intrinsic pontine glioma (DIPG)
      comprise a subset of HGG that arise in the brainstem almost exclusively in
      children. Genome-wide analyses of copy number imbalances previously showed that
      platelet-derived growth factor receptor alpha (PDGFRA) is the most frequent
      target of focal amplification in pediatric HGGs, including DIPGs. To determine
      whether PDGFRA is also targeted by more subtle mutations missed by copy number
      analysis, we sequenced all PDGFRA coding exons from a cohort of pediatric HGGs.
      Somatic-activating mutations were identified in 14.4% (13 of 90) of nonbrainstem
      pediatric HGGs and 4.7% (2 of 43) of DIPGs, including missense mutations and in
      frame deletions and insertions not previously described. Forty percent of tumors
      with mutation showed concurrent amplification, whereas 60% carried heterozygous
      mutations. Six different mutations impacting different domains all resulted in
      ligand-independent receptor activation that was blocked by small molecule
      inhibitors of PDGFR. Expression of mutants in p53-null primary mouse astrocytes
      conferred a proliferative advantage in vitro and generated HGGs in vivo with
      complete penetrance when implanted into brain. The gene expression signatures of
      these murine HGGs reflected the spectrum of human diffuse HGGs. PDGFRA intragenic
      deletion of exons 8 and 9 were previously shown in adult HGG, but were not
      detected in 83 nonbrainstem pediatric HGG and 57 DIPGs. Thus, a distinct spectrum
      of mutations confers constitutive receptor activation and oncogenic activity to
      PDGFRalpha in childhood HGG.

PMID- 23970479
TI  - mRNA splicing variants: exploiting modularity to outwit cancer therapy.
AB  - Systemic cancer therapy has traditionally exploited vulnerabilities in cancer
      cells, a strategy which has become more precise with the identification and
      targeting of driver oncogenes. However, persistent tumor growth due to primary
      (de novo) or secondary (acquired) resistance limits therapeutic efficacy for many
      patients. Alternative splicing is important for increasing the diversity of the
      cellular proteome, and is a process frequently deregulated during cancer
      development and progression. In cancer cells, diverse splicing alterations have
      been identified that eliminate protein domains or enzymatic activities required
      for efficacy of cancer therapies, promote gain of novel signaling functions that
      circumvent cancer therapies, and uncouple signaling pathways from upstream
      regulatory points that are blocked by cancer therapies. The mechanisms underlying
      these splicing changes range from stable alterations in gene sequence/structure
      to deregulation of splicing regulatory factors. In this review, the role of
      splice variants in cancer therapy resistance will be discussed, with examples of
      how mechanistic understanding of these processes has led to the development of
      novel strategies for therapy resensitization.

PMID- 23970480
TI  - Characterization of changes in total body composition for patients with head and
      neck cancer undergoing chemoradiotherapy using dual-energy x-ray absorptiometry.
AB  - BACKGROUND: Patients with head and neck cancer experience significant weight loss
      secondary to concurrent chemoradiotherapy (CCRT). Using dual-energy X-ray
      absorptiometry (DEXA) scans, we characterize total body composition changes
      during and after CCRT in order to develop novel clinical care models that will
      improve the patient's quality of life (QOL). METHODS: Sixty DEXA scans were
      obtained from 12 patients undergoing CCRT for locally advanced squamous cell head
      and neck cancer. DEXAs were performed at baseline, during treatment, completion
      of CCRT, and then 1 and 2 months posttreatment. RESULTS: Mean weight loss by
      treatment end was 9.5 kg (10.2%; p = .0002). On average, lean body mass (LBM)
      decreased 10.2% (p = .001), and fat body mass (FBM) decreased 11.1% (p = .001)
      during CCRT. LBM began to normalize after completion of treatment, whereas FBM
      continued to decline. CONCLUSION: Substantial loss of muscle and FBM occurs in
      patients undergoing CCRT for head and neck cancer. To prevent long-term
      disability and QOL decline after curative CCRT, clinical care interventions
      incorporating aggressive nutrition/exercise counseling are needed.

PMID- 23970481
TI  - Occupational diseases in the people's Republic of China between 2000 and 2010.
AB  - BACKGROUND: This study provides a description and analysis of the development of
      occupational diseases in China as recorded in the official statistics during the
      period 2000-2010, identifies major challenges, and explores possible solutions
      for prevention and control. METHODS: In-depth textual analysis and data analysis
      of China's annual national reports of occupational diseases, as well as of
      corresponding policy and regulation documents. RESULTS: The number of recorded
      cases of occupational diseases increased rapidly in China between 2000 and 2010.
      Pneumoconiosis was the most prevalent category of occupational diseases. Chemical
      poisonings accounted for 13% of the cases of occupational diseases. CONCLUSIONS:
      Difficulties in diagnosis and inefficient surveillance are major impediments to
      the mitigation of occupational diseases. The new definition of occupational
      disease has provided an opportunity to enlarge the Catalogue of Occupational
      Diseases. Improved coordination of the different chemical regulations meant to
      protect human health may also facilitate the prevention of occupational disease.

PMID- 23970482
TI  - Development of a novel assay for proprotein converting enzyme activity on a
      multiplex bead-based array system.
AB  - We describe the development of a novel, robust assay system for determining the
      changes in activity of proprotein converting enzymes. An assay for prolyl
      oligopeptidase (POP) activity was constructed using a peptide-streptavidin
      substrate coupled to magnetic microspheres and cleavage was detected by loss of
      streptavidin on the MAGPIX reader. Test analysis of postmortem pituitary extracts
      from schizophrenia patients showed an increase in POP activity compared to
      controls. The results were validated using both fluorometric and Western blot
      analyses for POP activity and immunoreactivity, respectively. The assays can be
      multiplexed for measuring the activity of multiple proprotein cleaving enzymes
      simultaneously in laboratory and clinical settings and should add valuable new
      information for conditions such as neuropsychiatric diseases, diabetes, endocrine
      dysfunction, and cancer, where effects on proteolysis of biologically active
      peptides play a key role.

PMID- 23970483
TI  - Jasmonate-dependent alkaloid biosynthesis in Catharanthus Roseus hairy root
      cultures is correlated with the relative expression of Orca and Zct transcription
      factors.
AB  - The effects of methyl jasmonate (MJ) dosage on terpenoid indole alkaloid (TIA)
      biosynthesis in Catharanthus roseus are correlated with the relative levels of
      specific MJ-responsive transcription factors. In this study, the expression of
      transcription factors (Orca, Zct, Gbf, Myc2, At-hook, and Wrky1), TIA pathway
      genes (G10h, Tdc, Str, and Sgd), and TIA metabolites (secologanin, strictosidine,
      and tabersonine) were investigated in C. roseus hairy root cultures elicited with
      a range of MJ dosages (0-1,000 uM) during mid-exponential growth. The highest
      production of TIA metabolites occurs at 250 MUM MJ, increasing by 150-370%
      compared with untreated controls. At this MJ dosage, the expression of the
      transcriptional activators (Orca) is dramatically increased (29-40 fold) while
      the levels of the transcriptional repressors (Zct) remain low (2-7 fold).
      Simultaneously, the expression of genes coding for key enzymes involved in TIA
      biosynthesis increases by 8-15 fold. In contrast, high MJ dosages (1,000 uM)
      inhibit the production of TIA metabolites. This dosage is correlated with
      elevated expression levels of Zct (up to 40-fold) relative to Orca (13-19-fold)
      and minimal induction of the TIA biosynthetic genes (0-6 fold). The significant
      changes in the expression of Orca and Zct with MJ dosage do not correspond to
      changes in the expression of the early-response transcription factors (AT-hook,
      Myc2, and Wrky1) believed to regulate Orca and Zct. In summary, these
      observations suggest that the dependence of alkaloid production on MJ dosage in
      C. roseus may be partly mediated through the relative levels of Orca and Zct
      family transcription factors.

PMID- 23970484
TI  - In vitro interaction between paromomycin sulphate and four drugs with
      leishmanicidal activity against three New World Leishmania species.
AB  - OBJECTIVES: To evaluate in vitro interactions between paromomycin sulphate and
      the antileishmanial drugs meglumine antimoniate, amphotericin B, miltefosine and
      azithromycin against intracellular Leishmania (Leishmania) infantum chagasi,
      Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis
      amastigotes in peritoneal mouse macrophages. METHODS: First, drug susceptibility
      was assessed in 3, 5 and 7 day assays, followed by drug interaction assays with a
      modified fixed-ratio method. An overall mean sum fractional inhibitory
      concentration (?FIC) was calculated for each combination and each Leishmania
      species. The nature of the interactions was classified as synergistic if the mean
      ?FIC was <= 0.5, indifferent if the mean ?FIC was >0.5-4.0 and antagonistic if
      the mean ?FIC was >4.0. RESULTS: In vitro synergism was observed for the
      combinations of paromomycin plus miltefosine [at 50% and 90% inhibitory
      concentrations (IC50 and IC90, respectively)] and paromomycin plus amphotericin B
      (at the IC90 level) against L. (L.) amazonensis, paromomycin plus meglumine
      antimoniate (at the IC50 and IC90 levels) and paromomycin plus amphotericin B (at
      the IC50 level) against L. (V.) braziliensis, and paromomycin plus miltefosine,
      paromomycin plus amphotericin B (both at the IC90 level) and paromomycin plus
      azithromycin (at the IC50 level) against L. (L) infantum chagasi. CONCLUSIONS:
      This work provides a preclinical dataset that supports future studies on
      multidrug treatment schedules against New World leishmaniasis.

PMID- 23970485
TI  - Evolution and molecular characterization of macrolide-resistant Streptococcus
      pneumoniae in Canada between 1998 and 2008.
AB  - OBJECTIVES: Studies were performed to assess resistance mechanisms, multidrug
      resistance (MDR), genetic relatedness, serotype distribution, heptavalent
      pneumococcal conjugate vaccine (PCV7) coverage and pili virulence factors among
      macrolide-resistant Streptococcus pneumoniae (MRSP) isolated from respiratory
      samples submitted to hospital laboratories across Canada from 1998 to 2008.
      METHODS: Isolates of MRSP (n = 1518) collected by the national surveillance
      studies CROSS (Canadian Respiratory Organism Susceptibility Study; 1998-2006) and
      CANWARD (Canadian Ward Surveillance Study; 2007-08) were tested using the CLSI
      broth microdilution method to establish antimicrobial susceptibilities. PCR was
      used to detect macrolide resistance genes [mef(A) and erm(B)] and pili virulence
      factors (type 1 pili and type 2 pili), the Quellung reaction was used to identify
      serotypes and PFGE was used to determine genetic relatedness. RESULTS: The
      prevalence of MRSP increased from 8% in 1998 to 22% in 2008 (P = 0.0001). MRSP
      were 51% mef(A) positive, 36% erm(B) positive, 8% dual mef(A) and erm(B) positive
      and 5% mef(A) and erm(B) negative. Dual mef(A)- and erm(B)-positive isolates
      increased in prevalence from 3% in 1998 to 19% in 2008 (P = 0.001). The
      prevalence of PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) decreased from 67%
      in 1998 to 31% in 2008 (P = 0.0072). The prevalence of serotype 19A, a non-PCV7
      serotype, increased by 15% from 1998 to 2008; isolates of serotype 19A were MDR,
      dual mef(A) and erm(B) positive, genetically related by PFGE and associated with
      the presence of pili virulence factors. CONCLUSIONS: From 1998 to 2008,
      respiratory isolates of MRSP in Canada increased significantly due primarily to
      the emergence and spread of serotypes 6A, 19A and other non-PCV7 serotypes.

PMID- 23970486
TI  - Reducing damage through Nrf-2.

PMID- 23970487
TI  - Understanding the vertical equity judgements underpinning health inequality
      measures.
AB  - The choice of income-related health inequality measures in comparative studies is
      often determined by custom and analytical concerns, without much explicit
      consideration of the vertical equity judgements underlying alternative measures.
      This note employs an inequality map to illustrate how these judgements determine
      the ranking of populations by health inequality. In particular, it is shown that
      relative indices of inequality in health attainments and shortfalls embody
      distinct vertical equity judgments, where each may represent ethically defensible
      positions in specific contexts. Further research is needed to explore people's
      preferences over distributions of income and health.

PMID- 23970488
TI  - Group sequential designs for three-arm 'gold standard' non-inferiority trials
      with fixed margin.
AB  - In the recent years there have been numerous publications on the design and the
      analysis of three-arm 'gold standard' noninferiority trials. Whenever feasible,
      regulatory authorities recommend the use of such three-arm designs including a
      test treatment, an active control, and a placebo. Nevertheless, it is desirable
      in many respects, for example, ethical reasons, to keep the placebo group size as
      small as possible. We first give a short overview on the fixed sample size design
      of a three-arm noninferiority trial with normally distributed outcomes and a
      fixed noninferiority margin. An optimal single stage design is derived that
      should serve as a benchmark for the group sequential designs proposed in the main
      part of this work. It turns out, that the number of patients allocated to placebo
      is substantially low for the optimal design. Subsequently, approaches for group
      sequential designs aiming to further reduce the expected sample sizes are
      presented. By means of choosing different rejection boundaries for the respective
      null hypotheses, we obtain designs with quite different operating
      characteristics. We illustrate the approaches via numerical calculations and a
      comparison with the optimal single stage design. Furthermore, we derive
      approximately optimal boundaries for different goals, for example, to reduce the
      overall average sample size. The results show that the implementation of a group
      sequential design further improves the optimal single stage design. Besides cost
      and time savings, the possible early termination of the placebo arm is a key
      advantage that could help to overcome ethical concerns.

PMID- 23970489
TI  - Proteomic identification of Listeria monocytogenes surface-associated proteins.
AB  - This study aimed to identify proteins exposed on the surface of Listeria
      monocytogenes cells for diagnostic reagent development. Brief trypsin treatment
      of L. monocytogenes cells followed by peptide separation and identification by
      nano-LC and online-MS/MS was performed. In parallel, as a negative control,
      proteins secreted into the digest buffer as well as proteins from cell lysis were
      identified. One hundred and seventy-four proteins were identified in at least two
      of three trials in either the negative control or during cell digest. Nineteen
      surface, 21 extracellularly secreted, 132 cytoplasmic, and two phage proteins
      were identified. Immunofluorescence microscopy of L. monocytogenes cells revealed
      the surface localization of two potential candidates for L. monocytogenes
      isolation and detection: lipoprotein LMOf2365_0546 and PBPD1 (LMOf2365_2742). In
      this report, we present the first data set of surface-exposed L. monocytogenes
      proteins currently available. The data have been deposited to the ProteomeXchange
      Consortium with identifier PXD000035.

PMID- 23970490
TI  - Strategy for selecting disposable bags for cell culture media applications based
      on a root-cause investigation.
AB  - The use of disposable bags for cell culture media storage has grown significantly
      in the past decade. Some of the key advantages of using disposable bags relative
      to non-disposable containers include increased product throughput, decreased
      cleaning validation costs, reduced risk of cross contamination and lower facility
      costs. As the scope of use of disposable bags for cell culture applications
      increases, problematic bags and scenarios should be identified and addressed to
      continue improving disposables technologies and meet the biotech industry's
      needs. In this article, we examine a cell culture application wherein media
      stored in disposable bags is warmed at 37 degrees C before use for cell culture
      operations. A problematic bag film was identified through a prospective and
      retrospective cell culture investigation. The investigation provided information
      on the scope and variation of the issue with respect to different Chinese hamster
      ovary (CHO) cell lines, cell culture media, and application-specific parameters.
      It also led to the development of application-specific test methods and enabled a
      strategy for disposable bag film testing. The strategy was implemented for
      qualifying an alternative bag film for use in our processes. In this test
      strategy, multiple lots of 13 bag film types, encompassing eight vendors were
      evaluated using a three round, cell culture-based test strategy. The test
      strategy resulted in the determination of four viable bag film options based on
      the technical data. The results of this evaluation were used to conclude that a
      volatile or air-quenched compound, likely generated by gamma irradiation of the
      problematic bag film, negatively impacted cell culture performance.

PMID- 23970491
TI  - Herpes simplex virus type 1 encephalitis and unusual retinitis in a patient with
      systemic lupus erythematosus.
AB  - In this report we discuss a case of a patient with systemic lupus erythematosus
      who developed herpes simplex virus type 1(HSV-1) infection presenting with
      encephalitis as well as necrotic and non-necrotic retinitis. The patient
      presented with typical clinical symptoms and radiologic abnormalities consistent
      with HSV-1 encephalitis and HSV-1 retinitis in patients with HIV infection, but
      lacked cerebrospinal fluid pleocytosis and had bilateral retinitis with poor
      visual acuity. To the best of our knowledge, this is the first such case reported
      in the literature. 

PMID- 23970492
TI  - Psychodynamic interventions in cancer care II: a qualitative analysis of the
      therapists' reports.
AB  - BACKGROUND: To investigate the focus of psychodynamic-oriented interventions in
      cancer patients by means of a qualitative analysis of the therapists' reports.
      METHODS: One hundred thirty-five reports collected within a controlled
      psychotherapy trial were analyzed; the themes addressed during the intervention
      were classified in categories reflecting the focus of the intervention and
      correlated with sociodemographic and medical data and type of intervention.
      RESULTS: Twenty main themes were identified and classified in two categories:
      category 1 corresponded to interventions based on expression and support, and
      category 2 to interventions based on introspection, with subcategory 2.1 focusing
      on the patient's psychological functioning and subcategory 2.2 focusing on his
      way to engage and communicate in relationships. While the most frequently
      addressed theme was related to the diagnosis of cancer (N = 102/576; 22.6%), the
      majority of themes were related to other concerns (N = 446/576; 77.4%). Half of
      the interventions (50.4%) were classified in category 1, 27.4% in category 2.1,
      and 9.6% in category 2.2. Patients of category 1 entered less often brief
      psychotherapy (step 2 of the intervention) and more frequently suffered from
      advances disease. CONCLUSIONS: A wide variety of themes are addressed in
      psychodynamic interventions in the oncology setting, illustrating that cancer is
      not the only focus of therapy. Other themes reflect different psychological
      difficulties triggered by the disease. This study illustrates that cancer
      patients have different needs, which surpass the event of the disease. Early
      clarification and comprehension of the demand may therefore be beneficial to
      adjust the therapeutic approach.

PMID- 23970493
TI  - Proteomics of CaCO3 biomineral-associated proteins: how to properly address their
      analysis.
AB  - In a recent editorial (Proc. Natl. Acad. Sci., 2013 110, E2144-E2146) and
      elsewhere, questions have been raised regarding the experimental practices in
      relation to the proteomic analysis of organic matrices associated to the
      biomineralized CaCO3 skeletons of metazoans such as molluscan shells and coral
      skeletons. Indeed, although the use of new high sensitivity MS technology
      potentially allows to identify a greater number of proteins, it is also equally
      (or even more) sensitive to contamination of residual proteins from soft tissues,
      which are in close contact with the biomineral. Based on our own past and present
      experimental know-how-observations that are reproducible and coherent with the
      current understanding of extracellular biomineralization processes-we are
      convinced that a careful and appropriate cleaning of biominerals prior to any
      analysis is crucial for accurate proteomic investigations and subsequent
      pertinent interpretation of the results. Our goal is to alert the scientific
      community about the associated bias that definitely should be avoided, and to
      provide critical recommendations on sample preparation and experimental design,
      in order to better take advantage of the aptness of proteomic approaches aiming
      at improving our understanding of the molecular mechanisms in biomineralization. 

PMID- 23970494
TI  - Model selection of generalized estimating equations with multiply imputed
      longitudinal data.
AB  - Longitudinal data often encounter missingness with monotone and/or intermittent
      missing patterns. Multiple imputation (MI) has been popularly employed for
      analysis of missing longitudinal data. In particular, the MI-GEE method has been
      proposed for inference of generalized estimating equations (GEE) when missing
      data are imputed via MI. However, little is known about how to perform model
      selection with multiply imputed longitudinal data. In this work, we extend the
      existing GEE model selection criteria, including the "quasi-likelihood under the
      independence model criterion" (QIC) and the "missing longitudinal information
      criterion" (MLIC), to accommodate multiple imputed datasets for selection of the
      MI-GEE mean model. According to real data analyses from a schizophrenia study and
      an AIDS study, as well as simulations under nonmonotone missingness with moderate
      proportion of missing observations, we conclude that: (i) more than a few imputed
      datasets are required for stable and reliable model selection in MI-GEE analysis;
      (ii) the MI-based GEE model selection methods with a suitable number of
      imputations generally perform well, while the naive application of existing model
      selection methods by simply ignoring missing observations may lead to very poor
      performance; (iii) the model selection criteria based on improper (frequentist)
      multiple imputation generally performs better than their analogies based on
      proper (Bayesian) multiple imputation. 

PMID- 23970495
TI  - Characterization of a group of pyrroloquinoline quinone-dependent dehydrogenases
      that are involved in the conversion of L-sorbose to 2-Keto-L-gulonic acid in
      Ketogulonicigenium vulgare WSH-001.
AB  - Ketogulonicigenium vulgare WSH-001 is an industrial strain used for vitamin C
      production. Based on genome sequencing and pathway analysis of the bacterium,
      some of its potential pyrroloquinoline quinone (PQQ)-dependent dehydrogenases
      were predicted, including KVU_pmdA_0245, KVU_2142, KVU_2159, KVU_1366, KVU_0203,
      KVU_0095, and KVU_pmdB_0115. BLAST and function domain searches showed that
      enzymes encoded by these genes may act as putative PQQ-dependent L-sorbose
      dehydrogenases (SDH) or L-sorbosone dehydrogenases (SNDH). To validate whether
      these dehydrogenases are PQQ-dependent or not, these seven putative dehyrogenases
      were overexpressed in Escherichia coli BL21 (DE3) and purified for
      characterization. Biochemical and kinetic characterization of the purified
      proteins have led to the identification of seven enzymes that possess the ability
      to oxidize L-sorbose or L-sorbosone to varying degrees. In addition, the
      dehydrogenation of sorbose in K. vulgare is validated to be PQQ dependent,
      identification of these PQQ-dependent dehydrogenases expanded the PQQ-dependent
      dehydrogenase family. Besides, the optimal combination of enzymes that could more
      efficiently catalyze the conversion of sorbose to gulonic acid was proposed.
      These are important in supporting the development of metabolic engineering
      strategies and engineering of efficient strains for one-step production of
      vitamin C in the future.

PMID- 23970496
TI  - Primary cutaneous aspergillosis due to Aspergillus tamarii in an immunocompetent
      host.
AB  - Primary cutaneous aspergillosis is a rare disease usually caused by Aspergillus
      fumigatus, Aspergillus flavus, Aspergillus terreus and Aspergillus ustus. It is
      usually seen in immunocompromised hosts, though some cases are also reported in
      immunocompetent hosts. We present a case of an immunocompetent farmer who
      presented with generalised nodules and plaques, mimicking erythema nodosum
      leprosum but turned out to be cutaneous aspergillosis caused by Aspergillus
      tamarii. The characteristic ascospores of Aspergillus species were found in skin
      lesions on fungus isolated in culture. The patient showed excellent response to
      antifungal therapy. 

PMID- 23970497
TI  - Bladder perivascular epithelioid cell tumours.
AB  - Perivascular epithelioid cell tumours, better known as PECOMAs, are a very
      uncommon pathological finding. In English medical literature it has rarely been
      reported. In the genitourinary system, mostly urinary bladder, the incidence is
      as low as 10 cases described since 2003 until now. In this case report, we
      present a urinary bladder PECOMA with a detailed pathological description and a
      review of literature. 

PMID- 23970499
TI  - Modeling 21Ne NMR parameters for carbon nanosystems.
AB  - The potential of nuclear magnetic resonance (NMR) technique in probing the
      structure of porous systems including carbon nanostructures filled with inert
      gases is analysed theoretically using accurate calculations of neon ((21) Ne)
      nuclear magnetic shieldings. The CBS estimates of (21) Ne NMR parameters were
      performed for single atom, its dimer and neon interacting with acetylene,
      ethylene and 1,3-cyclopentadiene. Several levels of theory including restricted
      Hartree-Fock (RHF), Moller-Plesset perturbation theory to the second order (MP2),
      density functional theory (DFT) with van Voorhis and Scuseria's t-dependent
      gradient-corrected correlation functional (VSXC), coupled cluster with single and
      doubles excitations (CCSD), with single, doubles and triples included in a
      perturbative way (CCSD(T)) and single, doubles and tripes excitations (CCSDT)
      combined with polarization-consistent aug-pcS-n series of basis sets were
      employed. The impact of neon confinement inside selected fullerene cages used as
      an NMR probe was studied at the RHF/pcS-2 level of theory. A sensitivity of neon
      probe to the proximity of multiple CC bonds in C2 H2 , C2 H4 , C5 H6 and inside
      C28 , C30 , C32 , C34 and C60 fullerenes was predicted from (21) Ne NMR
      parameters' changes. Copyright (c) 2013 John Wiley & Sons, Ltd. 

PMID- 23970500
TI  - Quantitative proteomics characterization on the antitumor effects of
      isodeoxyelephantopin against nasopharyngeal carcinoma.
AB  - Isolated from Elephantopus scaber L., a Chinese medicinal herb that is widely
      used to prevent and treat cancers in China, isodeoxyelephantopin (ESI) exerted
      antitumor effects on several cancer cells. However, its antitumor mechanism is
      still not clear. In this study, we found that ESI could induce G2/M arrest and
      subsequently stimulate cell apoptosis in dose- and time-dependent manners. We
      used SILAC quantitative proteomics to identify ESI-regulated proteins in cancer
      cells, and found that 124 proteins were significantly altered in expression. Gene
      ontology and Ingenuity Pathway Analysis revealed that these proteins were mainly
      involved in the regulation of oxidative stress and inflammation response.
      Functional studies demonstrated that ESI induced G2/M arrest and apoptosis by
      inducing ROS generation, and that antioxidant N-acetyl-l-cysteine could block the
      ESI-induced antitumor effects. Accumulated ROS resulted in DNA breakage,
      subsequent G2/M arrest and mitochondrial-mediated apoptosis. ESI upregulated the
      expression of anticancer inflammation factors IL-12a, IFN-alpha, and IFN-beta
      through ROS-dependent and independent pathways. The current work reveals that ESI
      exerts its antitumor effects through ROS-dependent DNA damage, mitochondrial
      mediated apoptosis mechanism and antitumor inflammation factor pathway. 

PMID- 23970501
TI  - Visualization and quantification of cerebral metabolic fluxes of glucose in awake
      mice.
AB  - Biotransformation of glucose in organs includes multiple pathways, while
      quantitative evaluation of percentages of its utilization for individual pathways
      and their spatial heterogeneity in vivo remain unknown. Imaging MS (IMS) and
      metabolomics combined with a focused microwave irradiation for rapidly fixing
      tissue metabolism allowed us to quantify and visualize metabolic fluxes of
      glucose-derived metabolites in the mouse brain in vivo. At 15 min after the
      intraperitoneal injection of (13) C6 -labeled glucose, the mouse brain was
      exposed to focused microwave irradiation, which can stop brain metabolism within
      1 s. Quantification of metabolic intermediates containing (13) C atoms revealed
      that a majority of the (13) C6 -glucose was diverted into syntheses of glutamate,
      lactate, and uridine diphosphate (UDP)-glucose. IMS showed that regions rich in
      glutaminergic neurons exhibited a large signal of (13) C2 -labeled glutamate. On
      the other hand, the midbrain region was enriched with an intensive (13) C6 
      labeled UDP-glucose signal, suggesting an active glycogen synthesis.
      Collectively, application of the current method makes it possible to examine the
      fluxes of glucose metabolism in a region-specific manner. 

PMID- 23970503
TI  - Can HPV immunisation cause ADEM? Two case reports and literature review.

PMID- 23970502
TI  - Application and a proposed modification of the 2010 McDonald criteria for the
      diagnosis of multiple sclerosis in a Canadian cohort of patients with clinically
      isolated syndromes.
AB  - BACKGROUND: The 2005 and 2010 McDonald criteria utilize magnetic resonance
      imaging (MRI) to provide evidence of disease dissemination in space (DIS) and
      time (DIT) for the diagnosis of multiple sclerosis (MS) in patients who have
      clinically isolated syndromes (CIS). METHODS: Data from 109 CIS patients not
      satisfying the 2005 criteria at entry into a randomized controlled minocycline
      trial were analyzed to determine the proportion who would have been diagnosed
      with MS at screening based on 2010 criteria. The impact of including symptomatic,
      as well as asymptomatic, MRI lesions to confirm DIT was also explored. RESULTS:
      Thirty percent (33/109) of patients, retrospectively, met the 2010 criteria for a
      diagnosis of MS at baseline. When both symptomatic and asymptomatic lesions were
      used to confirm DIT, three additional patients met the 2010 criteria. There was a
      significant 10.1% increase in the proportion of patients who met the 2010 DIS
      criteria, compared with the 2005 DIS criteria; however, two patients satisfied
      the 2005 DIS but not 2010 DIS criteria. CONCLUSION: Using 2010 McDonald criteria,
      30% of the CIS patients could be diagnosed with MS using a single MRI scan.
      Inclusion of symptomatic lesions in the DIT criteria further increases this
      proportion to 33%.

PMID- 23970504
TI  - The impact of diagnostic criteria for neuromyelitis optica in patients with MS: a
      10-year follow-up of the South Atlantic Project.
AB  - BACKGROUND: It is recognized that there is a particular geographic and ethnic
      distribution of neuromyelitis optica (NMO) among Caucasian and non-Caucasian
      populations. OBJECTIVE: To review the diagnoses of patients whom were enrolled in
      the South Atlantic Project, a Brazilian multiple sclerosis (MS) survey performed
      from 1995-1998, and to identify NMO and MS case frequencies. METHODS: We reviewed
      the data from a 10-year follow-up of MS patients. To apply the current diagnostic
      criteria, the neurologists were asked to collect clinical and laboratory data
      from the medical records of study patients treated from 1999-2009. RESULTS: The
      spectrum of inflammatory demyelinating disease in 322 patients (67% white; 33%
      African-Brazilian) was: 49 (15%) with NMO; 14 (4%) with NMO syndromes; 10 (3%)
      with acute disseminated encephalomyelitis (ADEM); one isolated tumefactive brain
      lesion; 249 (77%) with MS (151 with relapsing-remitting MS (RRMS), 70 with
      secondary progressive MS (SPMS) and 27 with primary progressive MS (PPMS)).
      Disability was more severe in NMO and PPMS. One-third of the NMO patients had
      died. CONCLUSIONS: The frequency of NMO was 6.8% in Sao Paulo and 20.5% in Rio de
      Janeiro, and mainly seen in persons of African descent, which strengthens the
      hypothesis of there being an ethnic association of this disease. We recommend
      that epidemiological studies on MS that were performed previously be reviewed
      again, to ensure more accurate diagnoses.

PMID- 23970505
TI  - Science to Practice: imaging cancer-associated fibroblasts--no innocent
      bystanders.
AB  - The era of stromal-based therapies is coming, and methods to image the stroma are
      likely to become vital to improved understanding of the intricate
      interrelationships of these cells. Because fibroblasts are so important for the
      initiation of cancer, stromal-based therapies may serve as preventive regimens in
      patients who are at high risk for recurrent disease. The method described by
      Vandsburger et al uses a reporter-gene magnetic resonance (MR) imaging-agent
      paradigm that withstands dilution from cell division while allowing imaging
      without ionizing radiation. The requirement for gene transfection makes near-term
      clinical translation unlikely, but the opportunities for studying cancer
      associated fibroblast activity in tumor models and observing and modulating their
      migratory behavior is an exciting prospect, one that is hoped to bring tangible
      benefits to patients with cancer.

PMID- 23970506
TI  - Blood oxygen level-dependent MR in renal disease: moving toward clinical utility.

PMID- 23970507
TI  - Development of wire localization for occult breast lesions: Boston remembrances.
AB  - In the 1970s, the four authors of this article each set up mammographic screening
      programs and independently developed preoperative needle-wire localization
      techniques at different Boston-area hospitals. These innovations, which
      facilitated surgical biopsy of nonpalpable abnormalities, helped establish and
      popularize mammography and have only minimally changed over the ensuing decades.
      This historical perspective shares personal anecdotes of the early development of
      mammography and mammographic wire localizations.

PMID- 23970508
TI  - Classification of diffuse lung diseases: why and how.
AB  - The understanding of complex lung diseases, notably the idiopathic interstitial
      pneumonias and small airways diseases, owes as much to repeated attempts over the
      years to classify them as to any single conceptual breakthrough. One of the many
      benefits of a successful classification scheme is that it allows workers, within
      and between disciplines, to be clear that they are discussing the same disease.
      This may be of particular importance in the recruitment of individuals for a
      clinical trial that requires a standardized and homogeneous study population.
      Different specialties require fundamentally different things from a
      classification: for epidemiologic studies, a classification that requires
      categorization of individuals according to histopathologic pattern is not usually
      practicable. Conversely, a scheme that simply divides diffuse parenchymal disease
      into inflammatory and noninflammatory categories is unlikely to further the
      understanding about the pathogenesis of disease. Thus, for some disease
      groupings, for example, pulmonary vasculopathies, there may be several
      appropriate classifications, each with its merits and demerits. There has been an
      interesting shift in the past few years, from the accepted primacy of
      histopathology as the sole basis on which the classification of parenchymal lung
      disease has rested, to new ways of considering how these entities relate to each
      other. Some inventive thinking has resulted in new classifications that
      undoubtedly benefit patients and clinicians in their endeavor to improve
      management and outcome. The challenge of understanding the logic behind current
      classifications and their shortcomings are explored in various examples of lung
      diseases.

PMID- 23970509
TI  - Breast ultrasonography: state of the art.
AB  - Ultrasonography (US) is an indispensable tool in breast imaging and is
      complementary to both mammography and magnetic resonance (MR) imaging of the
      breast. Advances in US technology allow confident characterization of not only
      benign cysts but also benign and malignant solid masses. Knowledge and
      understanding of current and emerging US technology, along with the application
      of meticulous scanning technique, is imperative for image optimization and
      diagnosis. The ability to synthesize breast US findings with multiple imaging
      modalities and clinical information is also necessary to ensure the best patient
      care. US is routinely used to guide breast biopsies and is also emerging as a
      supplemental screening tool in women with dense breasts and a negative mammogram.
      This review provides a summary of current state-of-the-art US technology,
      including elastography, and applications of US in clinical practice as an
      adjuvant technique to mammography, MR imaging, and the clinical breast
      examination. The use of breast US for screening, preoperative staging for breast
      cancer, and breast intervention will also be discussed.

PMID- 23970511
TI  - Case 197: malignant paraganglioma manifesting with calvarial metastases.

PMID- 23970512
TI  - Diagnostic performance of coronary CT angiography.

PMID- 23970513
TI  - Radiation dose reduction at multidetector CT.

PMID- 23970514
TI  - Does intravenous administration of gadoxetate disodium have any effect on breath
      hold times.

PMID- 23970515
TI  - Radiation dose of second-generation 320-detector row CT.

PMID- 23970518
TI  - Restricted adipogenesis in hypertrophic obesity: the role of WISP2, WNT, and
      BMP4.

PMID- 23970520
TI  - Does losartan prevent progression of early diabetic nephropathy in American
      Indians with type 2 diabetes?

PMID- 23970519
TI  - Nutrient-sensing mechanisms in the gut as therapeutic targets for diabetes.
AB  - The small intestine is traditionally viewed as an organ that mediates nutrient
      digestion and absorption. This view has recently been revised owing to the
      ability of the duodenum to sense nutrient influx and trigger negative feedback
      loops to inhibit glucose production and food intake to maintain metabolic
      homeostasis. Further, duodenal nutrient-sensing defects are acquired in diabetes
      and obesity, leading to increased glucose production. In contrast, jejunal
      nutrient sensing inhibits glucose production and mediates the early antidiabetic
      effect of bariatric surgery, and gut microbiota composition may alter intestinal
      nutrient-sensing mechanisms to regain better control of glucose homeostasis in
      diabetes and obesity in the long term. This perspective highlights nutrient
      sensing mechanisms in the gut that regulate glucose homeostasis and the potential
      of targeting gut nutrient-sensing mechanisms as a therapeutic strategy to lower
      blood glucose concentrations in diabetes. 

PMID- 23970521
TI  - Does caloric restriction alone explain the effects of Roux-en-Y gastric bypass on
      glucose metabolism? Not by a long limb.

PMID- 23970522
TI  - Pharmacogenetic perturbations in humans as a tool to generate mechanistic
      insight.

PMID- 23970523
TI  - Unraveling the mechanisms underlying olanzapine-induced insulin resistance.

PMID- 23970524
TI  - The diabetic brain during hypoglycemia: in the midst of plenty of lactate.

PMID- 23970527
TI  - Does the length dependency of airway smooth muscle force contribute to airway
      hyperresponsiveness?
AB  - Airway wall remodeling and lung hyperinflation are two typical features of asthma
      that may alter the contractility of airway smooth muscle (ASM) by affecting its
      operating length. The aims of this study were as follows: 1) to describe in
      detail the "length dependency of ASM force" in response to different spasmogens;
      and 2) to predict, based on morphological data and a computational model, the
      consequence of this length dependency of ASM force on airway responsiveness in
      asthmatic subjects who have both remodeled airway walls and hyperinflated lungs.
      Ovine tracheal ASM strips and human bronchial rings were isolated and stimulated
      to contract in response to increasing concentrations of spasmogens at three
      different lengths. Ovine tracheal strips were more sensitive and generated
      greater force at longer lengths in response to acetylcholine (ACh) and K(+).
      Equipotent concentrations of ACh were approximately a log less for ASM stretched
      by 30% and approximately a log more for ASM shortened by 30%. Similar results
      were observed in human bronchi in response to methacholine. Morphometric and
      computational analyses predicted that the ASM of asthmatic subjects may be
      elongated by 6.6-10.4% (depending on airway generation) due to remodeling and/or
      hyperinflation, which could increase ACh-induced force by 1.8-117.8% (depending
      on ASM length and ACh concentration) and enhance the increased resistance to
      airflow by 0.4-4,432.8%. In conclusion, elongation of ASM imposed by airway wall
      remodeling and/or hyperinflation may allow ASM to operate at a longer length and
      to consequently generate more force and respond to lower concentration of
      spasmogens. This phenomenon could contribute to airway hyperresponsiveness. 

PMID- 23970528
TI  - Combined administration of hyperbaric oxygen and hydroxocobalamin improves
      cerebral metabolism after acute cyanide poisoning in rats.
AB  - Hyperbaric oxygen therapy (HBOT) or intravenous hydroxocobalamin (OHCob) both
      abolish cyanide (CN)-induced surges in interstitial brain lactate and glucose
      concentrations. HBOT has been shown to induce a delayed increase in whole blood
      CN concentrations, whereas OHCob may act as an intravascular CN scavenger.
      Additionally, HBOT may prevent respiratory distress and restore blood pressure
      during CN intoxication, an effect not seen with OHCob administration. In this
      report, we evaluated the combined effects of HBOT and OHCob on interstitial
      lactate, glucose, and glycerol concentrations as well as lactate-to-pyruvate
      ratio in rat brain by means of microdialysis during acute CN poisoning.
      Anesthetized rats were allocated to three groups: 1) vehicle (1.2 ml isotonic
      NaCl intra-arterially); 2) potassium CN (5.4 mg/kg intra-arterially); 3)
      potassium CN, OHCob (100 mg/kg intra-arterially) and subsequent HBOT (284 kPa in
      90 min). OHCob and HBOT significantly attenuated the acute surges in interstitial
      cerebral lactate, glucose, and glycerol concentrations compared with the
      intoxicated rats given no treatment. Furthermore, the combined treatment resulted
      in consistent low lactate, glucose, and glycerol concentrations, as well as in
      low lactate-to-pyruvate ratios compared with CN intoxicated controls. In rats
      receiving OHCob and HBOT, respiration improved and cyanosis disappeared, with
      subsequent stabilization of mean arterial blood pressure. The present findings
      indicate that a combined administration of OHCob and HBOT has a beneficial and
      persistent effect on the cerebral metabolism during CN intoxication. 

PMID- 23970529
TI  - Aspirin augments carotid-cardiac baroreflex sensitivity during muscle
      mechanoreflex and metaboreflex activation in humans.
AB  - Muscle mechanoreflex activation decreases the sensitivity of carotid baroreflex
      (CBR)-heart rate (HR) control during local metabolite accumulation in humans.
      However, the contribution of thromboxane A2 (TXA2) toward this response is
      unknown. Therefore, the effect of inhibiting TXA2 production via low-dose aspirin
      on CBR-HR sensitivity during muscle mechanoreflex and metaboreflex activation in
      humans was examined. Twelve young subjects performed two trials during two
      visits, preceded by 7 days' low-dose aspirin (81 mg) or placebo. One trial
      involved 3-min passive calf stretch (mechanoreflex) during 7.5-min limb
      circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70%
      maximal voluntary contraction isometric calf exercise to accumulate metabolites
      during CO and stretch (mechanoreflex and metaboreflex). HR (ECG) and mean
      arterial pressure (Finometer) were recorded. CBR function was assessed using
      rapid neck pressures ranging from +40 to -80 mmHg. Aspirin significantly
      decreased baseline thromboxane B2 production by 84 +/- 4% (P < 0.05) but did not
      affect 6-keto prostaglandin F1alpha. Following aspirin, stretch with metabolite
      accumulation significantly augmented maximal gain (GMAX) and operating point gain
      (GOP) of CBR-HR (GMAX; -0.71 +/- 0.14 vs. -0.37 +/- 0.08 and GOP; -0.69 +/- 0.13
      vs. -0.35 +/- 0.12 beats.min(-1).mmHg(-1) for aspirin and placebo, respectively;
      P < 0.05). CBR-HR function curves were reset similarly with aspirin and placebo
      during stretch with metabolite accumulation. In conclusion, these findings
      suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent
      muscle mechanoreflex and metaboreflex activation in humans. This increased
      sensitivity appears linked to reduced TXA2 production, which likely plays a role
      in metabolite sensitization of muscle mechanoreceptors. 

PMID- 23970530
TI  - Resistance training improves indices of muscle insulin sensitivity and beta-cell
      function in overweight/obese, sedentary young men.
AB  - We examined the effects of RT on oral glucose tolerance test (OGTT)-derived
      indices of muscle insulin sensitivity, hepatic insulin resistance, beta-cell
      function, and skeletal muscle proteins related to glucose transport in
      overweight/obese, sedentary young men. Twenty-eight participants [median body
      mass index (BMI) 30.9 kg/m(2); age 22 yr] completed 12 wk of RT (3 sessions/wk)
      and were assessed for changes in OGTT-derived indices, resting metabolic rate,
      body composition, serum adipokines, and skeletal muscle protein content
      [hexokinase 2 (HK2), glucose transporter type 4 (GLUT4), RAC-beta
      serine/threonine-protein kinase (AKT2), glycogen synthase kinase 3beta, and
      insulin receptor substrate 1]. Individualized responses to RT were also
      evaluated. RT significantly improved insulin and glucose area under the curve
      (both P < 0.03). With the use of OGTT indices of insulin action, we noted
      improved muscle insulin sensitivity index (mISI; P = 0.03) and oral disposition
      index (P = 0.03). BMI, lean body mass (LBM), and relative strength also increased
      (all P < 0.03), as did skeletal muscle protein content of HK2, GLUT4, and AKT2
      (26-33%; all P < 0.02). Hepatic insulin resistance index, adiponectin, leptin,
      and total amylin did not change. Further analysis demonstrated the presence of
      highly individualized responsiveness to RT for glucose tolerance and other
      outcomes. RT improved oral indices of muscle insulin sensitivity and beta-cell
      function but not hepatic insulin resistance in overweight/obese young men. In
      addition to the increase in LBM, the improvements in insulin action may be due,
      in part, to increases in key insulin signaling proteins. 

PMID- 23970532
TI  - Dynamic change in hyoid muscle length associated with trajectory of hyoid bone
      during swallowing: analysis using 320-row area detector computed tomography.
AB  - Research on muscle activation patterns during swallowing has been limited. Newly
      developed 320-row area detector computed tomography (320-ADCT) has excellent
      spatial and temporal resolution, which facilitates identification of
      laryngopharyngeal structures and quantitative kinematic analysis of pharyngeal
      swallowing. We investigated muscle activity patterns by observing the changes in
      length of hyoid muscles. 320-ADCT was performed in 26 healthy males while
      swallowing. The following parameters were analyzed three-dimensionally: 1)
      origins and insertions of the stylohyoid, anterior and posterior digastric,
      mylohyoid, geniohyoid, and thyrohyoid muscles; and 2) movement of the hyoid bone.
      The stylohyoid, posterior digastric, and mylohyoid muscles began to shorten
      simultaneously during the initial stage of swallowing. The shortening of these
      muscles occurred during the upward movement of the hyoid bone. Subsequently, the
      geniohyoid, thyrohyoid, and anterior digastric muscles began to shorten,
      synchronizing with the forward movement of the hyoid bone. A significant
      correlation was observed between the shortened muscle lengths of the stylohyoid,
      posterior digastric, and mylohyoid muscles and the upward movement of the hyoid
      bone (r = 0.45-0.65). A correlation was also observed between the shortened
      muscle length of the geniohyoid muscle and the forward movement of the hyoid bone
      (r = 0.61). In this study, the sequence of muscle activity during pharyngeal
      swallowing remained constant. Serial shortening of the hyoid muscles influenced
      the trajectory of the hyoid bone. The stylohyoid, posterior digastric, and
      mylohyoid muscles initiated the swallowing reflex and contributed to upward
      movement of the hyoid bone. The geniohyoid is a key muscle in the forward
      movement of the hyoid bone. 

PMID- 23970531
TI  - No independent, but an interactive, role of calcium-activated potassium channels
      in human cutaneous active vasodilation.
AB  - In human cutaneous microvasculature, endothelium-derived hyperpolarizing factors
      (EDHFs) account for a large portion of vasodilation associated with local
      stimuli. Thus we sought to determine the role of EDHFs in active vasodilation
      (AVD) to passive heating in two protocols. Whole body heating was achieved using
      water-perfused suits (core temperature increase of 0.8-1.0 degrees C), and skin
      blood flow was measured using laser-Doppler flowmetry. In the first protocol,
      four sites were perfused continuously via microdialysis with: 1) control; 2)
      tetraethylammonium (TEA) to block calcium-activated potassium (KCa) channels, and
      thus the actions of EDHFs; 3) N-nitro-l-arginine methyl ester (l-NAME) to inhibit
      nitric oxide synthase (NOS); and 4) TEA + l-NAME (n = 8). Data are presented as
      percent maximal cutaneous vascular conductance (CVC). TEA had no effect on AVD
      (CVC during heated plateau: control 57.4 +/- 4.9% vs. TEA 63.2 +/- 5.2%, P =
      0.27), indicating EDHFs are not obligatory. l-NAME attenuated plateau CVC to 33.7
      +/- 5.4% (P < 0.01 vs. control); while TEA + l-NAME augmented plateau CVC
      compared with l-NAME alone (49.7 +/- 5.3%, P = 0.02). From these data, it appears
      combined blockade of EDHFs and NOS necessitates dilation through other means,
      possibly through inward rectifier (KIR) and/or ATP-sensitive (KATP) potassium
      channels. To test this second hypothesis, we measured AVD at the following sites
      (n = 8): 1) control, 2) l-NAME, 3) l-NAME + TEA, and 4) l-NAME + TEA + barium
      chloride (BaCl2; KIR and KATP blocker). The addition of BaCl2 to l-NAME + TEA
      reduced plateau CVC to 32.7 +/- 6.6% (P = 0.02 vs. l-NAME + TEA), which did not
      differ from the l-NAME site. These data combined demonstrate a complex interplay
      between vasodilatory pathways, with cross-talk between NO, KCa channels, and KIR
      and/or KATP channels. 

PMID- 23970533
TI  - Visualization and stereological characterization of individual rat lung acini by
      high-resolution X-ray tomographic microscopy.
AB  - The small trees of gas-exchanging pulmonary airways, which are fed by the most
      distal purely conducting airways, are called acini and represent the functional
      gas-exchanging units. The three-dimensional architecture of the acini has a
      strong influence on ventilation and particle deposition. Due to the difficulty in
      identifying individual acini on microscopic lung sections, the knowledge about
      the number of acini and their biological parameters, like volume, surface area,
      and number of alveoli per acinus, are limited. We developed a method to extract
      individual acini from lungs imaged by high-resolution synchrotron radiation-based
      X-ray tomographic microscopy and estimated their volume, surface area, and number
      of alveoli. Rat acini were isolated by semiautomatically closing the airways at
      the transition from conducting to gas-exchanging airways. We estimated a mean
      internal acinar volume of 1.148 mm(3), a mean acinar surface area of 73.9 mm(2),
      and a mean of 8,470 alveoli/acinus. Assuming that the acini are similarly sized
      throughout different regions of the lung, we calculated that a rat lung contains
      5,470 +/- 833 acini. We conclude that our novel approach is well suited for the
      fast and reliable characterization of a large number of individual acini in
      healthy, diseased, or transgenic lungs of different species, including humans. 

PMID- 23970534
TI  - Physiology in medicine: peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is an atherosclerotic condition that can
      provoke symptoms of leg pain ("intermittent claudication") during exercise.
      Because PAD is often observed with comorbid conditions such hypertension,
      dyslipidemia, diabetes, cigarette smoking, and/or physical inactivity, the
      pathophysiology of PAD is certainly complex and involves multiple organ systems.
      Patients with PAD are at high risk for myocardial infarction, stroke, and all
      cause mortality. For this reason, a better physiological understanding of the
      pathogenesis and treatment options for PAD patients is necessary and forms the
      basis of this Physiology in Medicine review. 

PMID- 23970535
TI  - State-dependent and reflex drives to the upper airway: basic physiology with
      clinical implications.
AB  - The root cause of the most common and serious of the sleep disorders is
      impairment of breathing, and a number of factors predispose a particular
      individual to hypoventilation during sleep. In turn, obstructive hypopneas and
      apneas are the most common of the sleep-related respiratory problems and are
      caused by dysfunction of the upper airway as a conduit for airflow. The
      overarching principle that underpins the full spectrum of clinical sleep-related
      breathing disorders is that the sleeping brain modifies respiratory muscle
      activity and control mechanisms and diminishes the ability to respond to
      respiratory distress. Depression of upper airway muscle activity and reflex
      responses, and suppression of arousal (i.e., "waking-up") responses to
      respiratory disturbance, can also occur with commonly used sedating agents (e.g.,
      hypnotics and anesthetics). Growing evidence indicates that the sometimes
      critical problems of sleep and sedation-induced depression of breathing and
      arousal responses may be working through common brain pathways acting on common
      cellular mechanisms. To identify these state-dependent pathways and reflex
      mechanisms, as they affect the upper airway, is the focus of this paper. Major
      emphasis is on the synthesis of established and recent findings. In particular,
      we specifically focus on 1) the recently defined mechanism of genioglossus muscle
      inhibition in rapid-eye-movement sleep; 2) convergence of diverse
      neurotransmitters and signaling pathways onto one root mechanism that may explain
      pharyngeal motor suppression in sleep and drug-induced brain sedation; 3) the
      lateral reticular formation as a key hub of respiratory and reflex drives to the
      upper airway. 

PMID- 23970536
TI  - Muscle immobilization and remobilization downregulates PGC-1alpha signaling and
      the mitochondrial biogenesis pathway.
AB  - Prolonged immobilization (IM) results in skeletal muscle atrophy accompanied by
      increased reactive oxygen species (ROS) generation, inflammation, and protein
      degradation. However, the biological consequence of remobilizing such muscle has
      been studied only sparsely. In this study, we examined the peroxisome
      proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha)-controlled
      mitochondrial biogenesis pathway and inflammatory response in mice subjected to 2
      wk of hindlimb IM followed by 5 days of remobilization (RM). We hypothesized that
      ROS generation and activation of redox-sensitive signaling pathways play
      important roles in the etiology of muscle injury. FVB/N mice (age 2 mo) were
      randomly assigned to either 14 days of IM by casting one of the hindlimbs (n =
      7), IM followed by 5 days of RM with casting removed (n = 7), or to a control
      group (Con; n = 7). Muscle to body weight ratios of three major leg muscles were
      significantly decreased as a result of IM. Two ubiquitin-proteasome pathway
      enzymes, muscle atrophy F-box (MAFb or atrogin-1) and muscle ring finger-1 (MuRF
      1), were upregulated with IM and maintained at high levels during RM. Protein
      contents of PGC-1alpha and nuclear respiratory factors 1 and 2 in tibialis
      anterior (TA) muscle were reduced by 50% (P < 0.01) in IM vs. Con, with no
      recovery observed during RM. IM suppressed mitochondrial transcription factor A
      and cytochrome-c content by 57% and 63% (P < 0.01), respectively, and cytochrome
      c oxidase activity by 58% (P < 0.05). Furthermore, mitochondrial DNA content was
      reduced by 71% (P < 0.01) with IM. None of these changes were reversed after RM.
      With RM, TA muscle showed a 2.3-fold (P < 0.05) higher H2O2 content and a 4-fold
      (P < 0.01) higher 8-isoprostane content compared with Con, indicating oxidative
      stress. Tumor necrosis factor-alpha and interleukin-6 levels in TA muscle were 4-
      and 3-fold higher (P < 0.05), respectively, in IM and RM vs. CON. The nuclear
      factor-kappaB (NF-kappaB) pathway activation was observed only after RM, but not
      after IM alone. These data indicate an increase in ROS generation during the
      initial phase of muscle RM that could activate the NF-kappaB pathway, and elicit
      inflammation and oxidative stress. These events may hinder muscle recovery from
      IM-induced mitochondrial deterioration and protein loss. 

PMID- 23970538
TI  - Episodic ventilation lowers the efficiency of pulmonary CO2 excretion.
AB  - The ventilation pattern of many ectothermic vertebrates, as well as hibernating
      and diving endotherms, is episodic where breaths are clustered in bouts
      interspersed among apneas of varying duration. Using mechanically ventilated,
      anesthetized freshwater turtles (Trachemys scripta), a species that normally
      exhibits this episodic ventilation pattern, we investigated whether episodic
      ventilation affects pulmonary gas exchange compared with evenly spaced breaths.
      In two separate series of experiments (a noninvasive and an invasive),
      ventilation pattern was switched from a steady state, with evenly spaced breaths,
      to episodic ventilation while maintaining overall minute ventilation (30 ml.min(
      1).kg(-1)). On switching to an episodic ventilation pattern of 10 clustered
      breaths, mean CO2 excretion rate was reduced by 6 +/- 5% (noninvasive protocol)
      or 20 +/- 8% (invasive protocol) in the first ventilation pattern cycle, along
      with a reduction in the respiratory exchange ratio. O2 uptake was either not
      affected or increased in the first ventilation pattern cycle, while neither heart
      rate nor overall pulmonary blood flow was significantly affected by the
      ventilation patterns. The results confirm that, for a given minute ventilation,
      episodic ventilation is intrinsically less efficient for CO2 excretion, thereby
      indicating an increase in the total bodily CO2 store in the protocol. Despite the
      apparent CO2 retention, mean arterial Pco2 only increased 1 Torr during the
      episodic ventilation pattern, which was concomitant with a possible reduction of
      respiratory quotient. This would indicate a shift in metabolism such that less
      CO2 is produced when the efficiency of excretion is reduced. 

PMID- 23970537
TI  - Acute exercise remodels mitochondrial membrane interactions in mouse skeletal
      muscle.
AB  - A unique property of mitochondria in mammalian cells is their ability to
      physically interact and undergo dynamic events of fusion/fission that remodel
      their morphology and possibly their function. In cultured cells, metabolic
      perturbations similar to those incurred during exercise influence mitochondrial
      fusion and fission processes, but it is unknown whether exercise acutely alters
      mitochondrial morphology and/or membrane interactions in vivo. To study this
      question, we subjected mice to a 3-h voluntarily exercise intervention following
      their normal physical activity patterns, and quantified mitochondrial morphology
      and membrane interactions in the soleus using a quantitative electron microscopy
      approach. A single exercise bout effectively decreased blood glucose (P < 0.05)
      and intramyocellular lipid content (P < 0.01), indicating increased muscle
      metabolic demand. The number of mitochondria spanning Z-lines and proportion of
      electron-dense contact sites (EDCS) between adjacent mitochondrial membranes were
      increased immediately after exercise among both subsarcolemmal (+116%, P < 0.05)
      and intermyofibrillar mitochondria (+191%, P < 0.001), indicating increased
      physical interactions. Mitochondrial morphology, and abundance of the
      mitochondrial pro-fusion proteins Mfn2 and OPA1 were unchanged. Collectively,
      these results support the notion that mitochondrial membrane dynamics are
      actively remodelled in skeletal muscle, which may be regulated by contractile
      activity and the metabolic state. Future studies are required to understand the
      implications of mitochondrial dynamics in skeletal muscle physiology during
      exercise and inactivity. 

PMID- 23970539
TI  - Unilateral nasal allergic reactions increase bilateral sinus eosinophil
      infiltration.
AB  - We have previously shown that unilateral nasal challenge with antigen causes an
      increase in the number of eosinophils in the ipsilateral maxillary sinus. Here we
      aimed to determine whether there was an eosinophil response in the contralateral
      maxillary sinus after unilateral nasal challenge with antigen. Twenty subjects
      with a history of seasonal allergic rhinitis and a positive nasal challenge to
      ragweed or grass allergens were studied outside of their allergy season.
      Catheters were placed in both maxillary sinuses and the subjects were challenged
      with antigen via the left nostril. The subjects recorded nasal symptoms before
      and after each allergen challenge and hourly for 8 h afterward. We performed
      nasal lavages of the nose and sinuses at the same time as symptoms were recorded.
      The lavages were analyzed for the number of eosinophils and levels of albumin.
      Subjects showed a symptomatic response to challenge accompanied by an influx of
      eosinophils into the nose and increased vascular permeability. The number of
      eosinophils increased in both maxillary sinuses. The total change from diluent in
      eosinophils during the late phase response was higher in the ipsilateral
      maxillary sinus (median = 8,505; range = 0-100,360) compared with the
      contralateral sinus (median = 1,596; range = -13,527-93,373; P = 0.03). We
      conclude that eosinophils increase in both maxillary sinuses after unilateral
      nasal challenge. We speculate that a central neurologic reflex initiated in the
      nose by the nasal challenge contributes to the bilateral eosinophil response in
      the maxillary sinuses. We further speculate that, since there are more
      eosinophils in the ipsilateral compared with the contralateral maxillary sinus,
      there is also an axonal reflex into the ipsilateral maxillary sinus that
      contributed to the eosinophil response. 

PMID- 23970540
TI  - Toxicological findings of synthetic cannabinoids in recreational users.
AB  - In recent years, several synthetic cannabinoid compounds have become popular
      recreational drugs of abuse because of their psychoactive properties. This paper
      presents toxicological findings of synthetic cannabinoids in whole blood from
      some cases of severe intoxication including quantitative data from recreational
      users and a fatal intoxication. Samples were analyzed by liquid chromatography
      tandem mass spectrometry in a scheduled multiple reaction mode after a basic
      liquid extraction. Twenty-nine synthetic cannabinoids were included in the
      method. In our data set of ~3000 cases, 28% were found positive for one or more
      synthetic cannabinoid(s). The most common finding was AM-2201. Most of the
      analytes had median concentrations of <0.5 ng/g in agreement with other published
      data. The emerging drugs MAM-2201 (n = 151) and UR-144 (n = 181) had mean
      (median) concentrations of 1.04 (0.37) and 1.26 (0.34), respectively. The
      toxicity of the synthetic cannabinoids seems to be worse than that of natural
      cannabis, probably owing to the higher potency and perhaps also to the presence
      of several different cannabinoids in the smoked incense and the difficulties of
      proper dosing. The acute toxic effects may under certain circumstances contribute
      to death.

PMID- 23970541
TI  - Supervised physical exercise improves endothelial function in patients with
      systemic lupus erythematosus.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of supervised
      physical exercise on endothelial function, ergospirometric test variables and
      disease activity in SLE patients. METHODS: We conducted a prospective study in
      which women with SLE who were available to perform physical exercise were
      allocated to the exercise group (EG) to practise supervised physical exercise for
      1 h three times per week for 16 weeks. Those who were not available for this
      activity were allocated to the control group (CG). Intervention consisted of
      walking at a heart rate corresponding to the ventilatory 1 threshold obtained
      from ergospirometry and monitored by a frequency meter. At baseline (T0) and
      after 16 weeks (T16), patients were assessed for endothelial function by brachial
      artery (flow-mediated dilation), ergospirometry and disease activity (SLEDAI).
      Statistical analysis was performed through normality tests, Student's t-test and
      non-parametric tests for data with non-normal distribution. P < 0.05 was
      considered significant. RESULTS: Eighteen patients were allocated in the EG and
      20 in the CG. After 16 weeks there was an increase in FMD in the EG [6.3 (6.7)%
      vs 14.1 (9.1)%, P = 0.006] without a change in the CG [8.4 (8.2)% vs 9.4 (5.7)%,
      P = 0.598]. Regarding the ergospirometric test, we found improvement in exercise
      tolerance [12.3 (2.4) vs 13.4 (2.6) min, P = 0.027], maximum speed [7.7 (1.0) vs
      8.3 (1.2) km/h, P = 0.027] and threshold speed [5.6 (0.7) vs 6.1 (0.9) km/h, P =
      0.005] in the EG without a difference in the CG. There was no difference in the
      SLEDAI score in both groups. CONCLUSION: Physical exercise is a useful strategy
      to improve endothelial function and aerobic capacity without worsening disease
      activity in SLE patients. TRIAL REGISTRATION; ClinicalTrials.gov
      (http://www.clinicaltrials.gov), NCT01712529.

PMID- 23970542
TI  - Immune mechanisms in polymyositis and dermatomyositis and potential targets for
      therapy.
AB  - PM and DM are characterized clinically by weakness and low endurance of skeletal
      muscle. Other organs are frequently involved, suggesting that idiopathic
      inflammatory myopathies (IIMs) are systemic inflammatory diseases. Involvement of
      immune mechanisms in IIMs is supported by the presence of T cells, macrophages
      and dendritic cells in muscle tissue, by the presence of autoantibodies and by
      HLA-DR being a strong genetic risk factor. T cells may have direct and indirect
      toxic effects on muscle fibres, causing muscle fibre necrosis and muscle
      weakness, but the target of the immune reaction is not known. A newly identified
      T cell subset, CD28(null) T cells, may have cytotoxic effects in the CD4(+) and
      CD8(+) T cell phenotype. These cells are apoptosis resistant and may contribute
      to treatment resistance. Several myositis-specific autoantibodies have been
      identified, but they are all directed against ubiquitously expressed autoantigens
      and the specificity of the T cell reactivity is not known. These autoantibodies
      are associated with distinct clinical phenotypes and some with distinct molecular
      pathways; e.g. sera from patients with anti-Jo-1 autoantibodies may activate the
      type I IFN system and these sera also contain high levels of B cell activating
      factor compared with other IIM subsets. The characterization of patients into
      subgroups based on autoantibody profiles seems to be a promising way to learn
      more about the specificities of the immune reactions. Careful phenotyping of
      infiltrating immune cells in muscle tissue before and after specific therapies
      and relating the molecular findings to clinical outcome measures may be another
      way to improve knowledge on specific immune mechanism in IIMs. Such information
      will be important for the development of new therapies. 

PMID- 23970543
TI  - The Crafoord Prize in polyarthritis 2013.

PMID- 23970544
TI  - Efficacy of tocilizumab for interstitial lung disease in an undifferentiated
      autoinflammatory disorder partially responsive to anakinra.

PMID- 23970545
TI  - Automated classification of RNA 3D motifs and the RNA 3D Motif Atlas.
AB  - The analysis of atomic-resolution RNA three-dimensional (3D) structures reveals
      that many internal and hairpin loops are modular, recurrent, and structured by
      conserved non-Watson-Crick base pairs. Structurally similar loops define RNA 3D
      motifs that are conserved in homologous RNA molecules, but can also occur at
      nonhomologous sites in diverse RNAs, and which often vary in sequence. To further
      our understanding of RNA motif structure and sequence variability and to provide
      a useful resource for structure modeling and prediction, we present a new method
      for automated classification of internal and hairpin loop RNA 3D motifs and a new
      online database called the RNA 3D Motif Atlas. To classify the motif instances, a
      representative set of internal and hairpin loops is automatically extracted from
      a nonredundant list of RNA-containing PDB files. Their structures are compared
      geometrically, all-against-all, using the FR3D program suite. The loops are
      clustered into motif groups, taking into account geometric similarity and
      structural annotations and making allowance for a variable number of bulged
      bases. The automated procedure that we have implemented identifies all hairpin
      and internal loop motifs previously described in the literature. All motif
      instances and motif groups are assigned unique and stable identifiers and are
      made available in the RNA 3D Motif Atlas (http://rna.bgsu.edu/motifs), which is
      automatically updated every four weeks. The RNA 3D Motif Atlas provides an
      interactive user interface for exploring motif diversity and tools for
      programmatic data access. 

PMID- 23970546
TI  - Mitochondrial protein BmPAPI modulates the length of mature piRNAs.
AB  - PIWI proteins and their associated PIWI-interacting RNAs (piRNAs) protect genome
      integrity by silencing transposons in animal germlines. The molecular mechanisms
      and components responsible for piRNA biogenesis remain elusive. PIWI proteins
      contain conserved symmetrical dimethylarginines (sDMAs) that are specifically
      targeted by TUDOR domain-containing proteins. Here we report that the sDMAs of
      PIWI proteins play crucial roles in PIWI localization and piRNA biogenesis in
      Bombyx mori-derived BmN4 cells, which harbor fully functional piRNA biogenesis
      machinery. Moreover, RNAi screenings for Bombyx genes encoding TUDOR domain
      containing proteins identified BmPAPI, a Bombyx homolog of Drosophila PAPI, as a
      factor modulating the length of mature piRNAs. BmPAPI specifically recognized
      sDMAs and interacted with PIWI proteins at the surface of the mitochondrial outer
      membrane. BmPAPI depletion resulted in 3'-terminal extensions of mature piRNAs
      without affecting the piRNA quantity. These results reveal the BmPAPI-involved
      piRNA precursor processing mechanism on mitochondrial outer membrane scaffolds. 

PMID- 23970547
TI  - Arginine as a general acid catalyst in serine recombinase-mediated DNA cleavage.
AB  - Members of the serine family of site-specific DNA recombinases use an unusual
      constellation of amino acids to catalyze the formation and resolution of a
      covalent protein-DNA intermediate. A recent high resolution structure of the
      catalytic domain of Sin, a particularly well characterized family member,
      provided a detailed view of the catalytic site. To determine how the enzyme might
      protonate and stabilize the 3'O leaving group in the strand cleavage reaction, we
      examined how replacing this oxygen with a sulfur affected the cleavage rate by WT
      and mutant enzymes. To facilitate direct comparison of the cleavage rates, key
      experiments used suicide substrates that prevented religation after cleavage. The
      catalytic defect associated with mutation of one of six highly conserved arginine
      residues, Arg-69 in Sin, was partially rescued by a 3' phosphorothiolate
      substrate. We conclude that Arg-69 has an important role in stabilizing the 3'O
      leaving group and is the prime candidate for the general acid that protonates the
      3'O, in good agreement with the position it occupies in the high resolution
      structure of the active site of Sin. 

PMID- 23970548
TI  - Pretreatment with pyridoxamine mitigates isolevuglandin-associated retinal
      effects in mice exposed to bright light.
AB  - The benefits of antioxidant therapy for treating age-related macular
      degeneration, a devastating retinal disease, are limited. Perhaps species other
      than reactive oxygen intermediates should be considered as therapeutic targets.
      These could be lipid peroxidation products, including isolevuglandins (isoLGs),
      prototypical and extraordinarily reactive gamma-ketoaldehydes that avidly bind to
      proteins, phospholipids, and DNA and modulate the properties of these
      biomolecules. We found isoLG adducts in aged human retina but not in the retina
      of mice kept under dim lighting. Hence, to test whether scavenging of isoLGs
      could complement or supplant antioxidant therapy, we exposed mice to bright light
      and found that this insult leads to retinal isoLG-adduct formation. We then
      pretreated mice with pyridoxamine, a B6 vitamer and efficient scavenger of gamma
      ketoaldehydes, and found that the levels of retinal isoLG adducts are decreased,
      and morphological changes in photoreceptor mitochondria are not as pronounced as
      in untreated animals. Our study demonstrates that preventing the damage to
      biomolecules by lipid peroxidation products, a novel concept in vision research,
      is a viable strategy to combat oxidative stress in the retina. 

PMID- 23970549
TI  - Full time course kinetics of the streptokinase-plasminogen activation pathway.
AB  - Our previously hypothesized mechanism for the pathway of plasminogen (Pg)
      activation by streptokinase (SK) was tested by the use of full time course
      kinetics. Three discontinuous chromogenic substrate initial rate assays were
      developed with different quenching conditions that enabled quantitation of the
      time courses of Pg depletion, plasmin (Pm) formation, transient formation of the
      conformationally activated SK.Pg* catalytic complex intermediate, formation of
      the SK.Pm catalytic complex, and the free concentrations of Pg, Pm, and SK.
      Analysis of full time courses of Pg activation by five concentrations of SK along
      with activity-based titrations of SK.Pg* and SK.Pm formation yielded rate and
      dissociation constants within 2-fold of those determined previously by continuous
      measurement of parabolic chromogenic substrate hydrolysis and fluorescence-based
      equilibrium binding. The results obtained with orthogonal assays provide
      independent support for a mechanism in which the conformationally activated
      SK.Pg* complex catalyzes an initial cycle of Pg proteolytic conversion to Pm that
      acts as a trigger. Higher affinity binding of the formed Pm to SK outcompetes Pg
      binding, terminating the trigger cycle and initiating the bullet catalytic cycle
      by the SK.Pm complex that converts the residual Pg into Pm. The new assays can be
      adapted to quantitate SK-Pg activation in the context of SK- or Pg-directed
      inhibitors, effectors, and SK allelic variants. To support this, we show for the
      first time with an assay specific for SK.Pg* that fibrinogen forms a ternary
      SK.Pg*.fibrinogen complex, which assembles with 200-fold enhanced SK.Pg*
      affinity, signaled by a perturbation of the SK.Pg* active site. 

PMID- 23970550
TI  - Secreted proteases control autolysin-mediated biofilm growth of Staphylococcus
      aureus.
AB  - Staphylococcus epidermidis, a commensal of humans, secretes Esp protease to
      prevent Staphylococcus aureus biofilm formation and colonization. Blocking S.
      aureus colonization may reduce the incidence of invasive infectious diseases;
      however, the mechanism whereby Esp disrupts biofilms is unknown. We show here
      that Esp cleaves autolysin (Atl)-derived murein hydrolases and prevents
      staphylococcal release of DNA, which serves as extracellular matrix in biofilms.
      The three-dimensional structure of Esp was revealed by x-ray crystallography and
      shown to be highly similar to that of S. aureus V8 (SspA). Both atl and sspA are
      necessary for biofilm formation, and purified SspA cleaves Atl-derived murein
      hydrolases. Thus, S. aureus biofilms are formed via the controlled secretion and
      proteolysis of autolysin, and this developmental program appears to be perturbed
      by the Esp protease of S. epidermidis. 

PMID- 23970551
TI  - Cooperative activation of the T-type CaV3.2 channel: interaction between Domains
      II and III.
AB  - T-type CaV3 channels are important mediators of Ca(2+) entry near the resting
      membrane potential. Little is known about the molecular mechanisms responsible
      for channel activation. Homology models based upon the high-resolution structure
      of bacterial NaV channels predict interaction between the S4-S5 helix of Domain
      II (IIS4-S5) and the distal S6 pore region of Domain II (IIS6) and Domain III
      (IIIS6). Functional intra- and inter-domain interactions were investigated with a
      double mutant cycle analysis. Activation gating and channel kinetics were
      measured for 47 single mutants and 20 pairs of mutants. Significant coupling
      energies (DeltaDeltaG(interact) >= 1.5 kcal mol(-1)) were measured for 4 specific
      pairs of mutants introduced between IIS4-S5 and IIS6 and between IIS4-S5 and
      IIIS6. In agreement with the computer based models, Thr-911 in IIS4-S5 was
      functionally coupled with Ile-1013 in IIS6 during channel activation. The
      interaction energy was, however, found to be stronger between Val-907 in IIS4-S5
      and Ile-1013 in IIS6. In addition Val-907 was significantly coupled with Asn-1548
      in IIIS6 but not with Asn-1853 in IVS6. Altogether, our results demonstrate that
      the S4-S5 and S6 helices from adjacent domains are energetically coupled during
      the activation of a low voltage-gated T-type CaV3 channel.

PMID- 23970553
TI  - The epithelial calcium channel TRPV5 is regulated differentially by klotho and
      sialidase.
AB  - The transient receptor potential vanilloid type 5 (TRPV5) Ca(2+) channel
      facilitates transcellular Ca(2+) transport in the distal convoluted tubule (DCT)
      of the kidney. The channel is glycosylated with a complex type N-glycan and it
      has been postulated that hydrolysis of the terminal sialic acid(s) stimulate
      TRPV5 activity. The present study delineates the role of the N-glycan in TRPV5
      activity using biochemical assays in Human Embryonic Kidney 293 cells expressing
      TRPV5, isoelectric focusing and total internal reflection fluorescent microscopy.
      The anti-aging hormone klotho and other glycosidases stimulate TRPV5-dependent
      Ca(2+) uptake. Klotho was found to increase the plasma membrane stability of
      TRPV5, via the TRPV5 N-glycan. Sialidase mimicked this stimulatory action.
      However, this effect was independent of the N-glycosylation state of TRPV5, since
      the N-glycosylation mutant (TRPV5(N358Q)) was activated to the same extent. We
      showed that the increased TRPV5 activity after sialidase treatment is caused by
      inhibition of lipid raft-mediated internalization. In addition, sialidase
      modified the N-glycan of transferrin, a model glycoprotein, differently from
      klotho. Previous studies showed that after klotho treatment, galectin-1 binds the
      TRPV5 N-glycan and thereby increases TRPV5 activity. However, galectin-3, but not
      galectin-1, was expressed in the DCT. Furthermore, an increase in TRPV5-mediated
      Ca(2+) uptake was detected after galectin-3 treatment. In conclusion, two
      distinct TRPV5 stimulatory mechanisms were demonstrated; a klotho-mediated effect
      that is dependent on the N-glycan of TRPV5 and a sialidase-mediated stimulation
      that is lipid raft-dependent and independent of the N-glycan of TRPV5. 

PMID- 23970552
TI  - Transcription factor Reb1p regulates DGK1-encoded diacylglycerol kinase and lipid
      metabolism in Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, the DGK1-encoded diacylglycerol kinase
      catalyzes the CTP-dependent phosphorylation of diacylglycerol to form
      phosphatidate. This enzyme, in conjunction with PAH1-encoded phosphatidate
      phosphatase, controls the levels of phosphatidate and diacylglycerol for
      phospholipid synthesis, membrane growth, and lipid droplet formation. In this
      work, we showed that a functional level of diacylglycerol kinase is regulated by
      the Reb1p transcription factor. In the electrophoretic mobility shift assay,
      purified recombinant Reb1p was shown to specifically bind its consensus
      recognition sequence (CGGGTAA, -166 to -160) in the DGK1 promoter. Analysis of
      cells expressing the PDGK1-lacZ reporter gene showed that mutations (GT->TG) in
      the Reb1p-binding sequence caused an 8.6-fold reduction in beta-galactosidase
      activity. The expression of DGK1(reb1), a DGK1 allele containing the Reb1p
      binding site mutation, was greatly lower than that of the wild type allele, as
      indicated by analyses of DGK1 mRNA, Dgk1p, and diacylglycerol kinase activity. In
      the presence of cerulenin, an inhibitor of de novo fatty acid synthesis, the
      dgk1Delta mutant expressing DGK1(reb1) exhibited a significant defect in growth
      as well as in the synthesis of phospholipids from triacylglycerol mobilization.
      Unlike DGK1, the DGK1(reb1) expressed in the dgk1Delta pah1Delta mutant did not
      result in the nuclear/endoplasmic reticulum membrane expansion, which occurs in
      cells lacking phosphatidate phosphatase activity. Taken together, these results
      indicate that the Reb1p-mediated regulation of diacylglycerol kinase plays a
      major role in its in vivo functions in lipid metabolism. 

PMID- 23970555
TI  - Why Am I Studying Neuroscience When I Have a Disease Science Can't Explain: A
      Brief Synopsis From My Book Life Insane: My Memoir-Making of the Madman (Case
      Number: TXu001850659, US Copyright Office, Date: February 2, 2013).

PMID- 23970554
TI  - Inflammatory cytokines induce a unique mineralizing phenotype in mesenchymal stem
      cells derived from human bone marrow.
AB  - Bone marrow contains mesenchymal stem cells (MSCs) that can differentiate along
      multiple mesenchymal lineages. In this capacity they are thought to be important
      in the intrinsic turnover and repair of connective tissues while also serving as
      a basis for tissue engineering and regenerative medicine. However, little is
      known of the biological responses of human MSCs to inflammatory conditions. When
      cultured with IL-1beta, marrow-derived MSCs from 8 of 10 human subjects deposited
      copious hydroxyapatite, in which authenticity was confirmed by Fourier transform
      infrared spectroscopy. Transmission electron microscopy revealed the production
      of fine needles of hydroxyapatite in conjunction with matrix vesicles. Alkaline
      phosphatase activity did not increase in response to inflammatory mediators, but
      PPi production fell, reflecting lower ectonucleotide pyrophosphatase activity in
      cells and matrix vesicles. Because PPi is the major physiological inhibitor of
      mineralization, its decline generated permissive conditions for hydroxyapatite
      formation. This is in contrast to MSCs treated with dexamethasone, where PPi
      levels did not fall and mineralization was fuelled by a large and rapid increase
      in alkaline phosphatase activity. Bone sialoprotein was the only osteoblast
      marker strongly induced by IL-1beta; thus these cells do not become osteoblasts
      despite depositing abundant mineral. RT-PCR did not detect transcripts indicative
      of alternative mesenchymal lineages, including chondrocytes, myoblasts,
      adipocytes, ligament, tendon, or vascular smooth muscle cells. IL-1beta
      phosphorylated multiple MAPKs and activated nuclear factor-kappaB (NF-kappaB).
      Certain inhibitors of MAPK and PI3K, but not NF-kappaB, prevented mineralization.
      The findings are of importance to soft tissue mineralization, tissue engineering,
      and regenerative medicine. 

PMID- 23970556
TI  - Schizophrenia and the sense of self.
AB  - Sense of self (SOS)--understood as the foundation upon which individuals
      experience their daily lives--has been increasingly investigated in
      schizophrenia. A disrupted SOS is thought to represent a platform for the
      experience of psychiatric symptoms, social cognitive deficits, and other
      abnormalities of consciousness. Few studies, however, have investigated the
      specificity of disrupted SOS to schizophrenia. The primary objective of the
      present study was to test the hypothesis that SOS is deficient in schizophrenia
      patients compared to both nonpsychiatric controls and patients with psychotic
      bipolar disorder. Using select scales from the Assessment of Self Descriptions,
      the present study assessed SOS from spontaneous narratives provided by
      schizophrenia patients (N = 50), bipolar patients with psychotic features (N =
      17), and nonpsychiatric controls (N = 24). Our findings indicate that facets of
      SOS-in particular, certain aspects of agency and relatedness to others-are
      deficient in schizophrenia compared to nonpsychiatric controls and bipolar
      patients with psychotic features, even when overall level of functioning and
      psychiatric symptoms are accounted for. Implications of these results are
      discussed.

PMID- 23970557
TI  - Molecular validation of the schizophrenia spectrum.
AB  - BACKGROUND: Early descriptive work and controlled family and adoption studies
      support the hypothesis that a range of personality and nonschizophrenic psychotic
      disorders aggregate in families of schizophrenic probands. Can we validate, using
      molecular polygene scores from genome-wide association studies (GWAS), this
      schizophrenia spectrum? METHODS: The predictive value of polygenic findings
      reported by the Psychiatric GWAS Consortium (PGC) was applied to 4 groups of
      relatives from the Irish Study of High-Density Schizophrenia Families (ISHDSF; N
      = 836) differing on their assignment within the schizophrenia spectrum. Genome
      wide single nucleotide polymorphism data for affected and unaffected relatives
      were used to construct per-individual polygene risk scores based on the PGC stage
      I results. We compared mean polygene scores in the ISHDSF with mean scores in
      ethnically matched population controls (N = 929). RESULTS: The schizophrenia
      polygene score differed significantly across diagnostic categories and was
      highest in those with narrow schizophrenia spectrum, lowest in those with no
      psychiatric illness, and in-between in those classified in the intermediate,
      broad, and very broad schizophrenia spectrum. Relatives of all of these groups of
      affected subjects, including those with no diagnosis, had schizophrenia polygene
      scores significantly higher than the control sample. CONCLUSIONS: In the
      relatives of high-density families, the observed pattern of enrichment of
      molecular indices of schizophrenia risk suggests an underlying, continuous
      liability distribution and validates, using aggregate common risk alleles, a
      genetic basis for the schizophrenia spectrum disorders. In addition, as predicted
      by genetic theory, nonpsychotic members of multiply-affected schizophrenia
      families are significantly enriched for replicated, polygenic risk variants
      compared with the general population.

PMID- 23970559
TI  - Topotactic interconversion of nanoparticle superlattices.
AB  - The directed assembly of nanoparticle building blocks is a promising method for
      generating sophisticated three-dimensional materials by design. In this work, we
      have used DNA linkers to synthesize nanoparticle superlattices that have greater
      complexity than simple binary systems using the process of topotactic
      intercalation-the insertion of a third nanoparticle component at predetermined
      sites within a preformed binary lattice. Five distinct crystals were synthesized
      with this methodology, three of which have no equivalent in atomic or molecular
      crystals, demonstrating a general approach for assembling highly ordered ternary
      nanoparticle superlattices whose structures can be predicted before their
      synthesis. Additionally, the intercalation process was demonstrated to be
      completely reversible; the inserted nanoparticles could be expelled into solution
      by raising the temperature, and the ternary superlattice could be recovered by
      cooling. 

PMID- 23970558
TI  - Circadian gene Bmal1 regulates diurnal oscillations of Ly6C(hi) inflammatory
      monocytes.
AB  - Circadian clocks have evolved to regulate physiologic and behavioral rhythms in
      anticipation of changes in the environment. Although the molecular clock is
      present in innate immune cells, its role in monocyte homeostasis remains unknown.
      Here, we report that Ly6C(hi) inflammatory monocytes exhibit diurnal variation,
      which controls their trafficking to sites of inflammation. This cyclic pattern of
      trafficking confers protection against Listeria monocytogenes and is regulated by
      the repressive activity of the circadian gene Bmal1. Accordingly, myeloid cell
      specific deletion of Bmal1 induces expression of monocyte-attracting chemokines
      and disrupts rhythmic cycling of Ly6C(hi) monocytes, predisposing mice to
      development of pathologies associated with acute and chronic inflammation. These
      findings have unveiled a critical role for BMAL1 in controlling the diurnal
      rhythms in Ly6C(hi) monocyte numbers. 

PMID- 23970560
TI  - The molecular trigger for high-speed wing beats in a bee.
AB  - The high-frequency wing beat of higher-order insects is driven by self-sustained
      oscillations of constantly activated flight muscles. However, whether its
      underlying mechanism is based on flight muscle-specific features or on
      preexisting contractile functions is unknown. Here, we recorded X-ray diffraction
      movies, at a rate of 5000 frames/second, simultaneously from the two antagonistic
      flight muscles of bumblebees during wing beat. Signals that occurred at the right
      timing for triggering each wing-beat stroke were resolved in both muscles. The
      signals likely reflect stretch-induced myosin deformation, which would also
      enhance force in vertebrate muscles. The results suggest that insects use a
      refined preexisting force-enhancing mechanism for high-frequency wing beat,
      rather than developing a novel mechanism. 

PMID- 23970561
TI  - Conserved regulation of cardiac calcium uptake by peptides encoded in small open
      reading frames.
AB  - Small open reading frames (smORFs) are short DNA sequences that are able to
      encode small peptides of less than 100 amino acids. Study of these elements has
      been neglected despite thousands existing in our genomes. We and others
      previously showed that peptides as short as 11 amino acids are translated and
      provide essential functions during insect development. Here, we describe two
      peptides of less than 30 amino acids regulating calcium transport, and hence
      influencing regular muscle contraction, in the Drosophila heart. These peptides
      seem conserved for more than 550 million years in a range of species from flies
      to humans, in which they have been implicated in cardiac pathologies. Such
      conservation suggests that the mechanisms for heart regulation are ancient and
      that smORFs may be a fundamental genome component that should be studied
      systematically. 

PMID- 23970562
TI  - An atomic clock with 10(-18) instability.
AB  - Atomic clocks have been instrumental in science and technology, leading to
      innovations such as global positioning, advanced communications, and tests of
      fundamental constant variation. Timekeeping precision at 1 part in 10(18) enables
      new timing applications in relativistic geodesy, enhanced Earth- and space-based
      navigation and telescopy, and new tests of physics beyond the standard model.
      Here, we describe the development and operation of two optical lattice clocks,
      both using spin-polarized, ultracold atomic ytterbium. A measurement comparing
      these systems demonstrates an unprecedented atomic clock instability of 1.6 * 10(
      18) after only 7 hours of averaging. 

PMID- 23970564
TI  - Cerebrospinal-fluid-derived immunoglobulin G of different multiple sclerosis
      patients shares mutated sequences in complementarity determining regions.
AB  - B lymphocytes play a pivotal role in multiple sclerosis pathology, possibly via
      both antibody-dependent and -independent pathways. Intrathecal immunoglobulin G
      in multiple sclerosis is produced by clonally expanded B-cell populations. Recent
      studies indicate that the complementarity determining regions of immunoglobulins
      specific for certain antigens are frequently shared between different
      individuals. In this study, our main objective was to identify specific proteomic
      profiles of mutated complementarity determining regions of immunoglobulin G
      present in multiple sclerosis patients but absent in healthy controls. To achieve
      this objective, we purified immunoglobulin G from the cerebrospinal fluid of 29
      multiple sclerosis patients and 30 healthy controls and separated the
      corresponding heavy and light chains via SDS-PAGE. Subsequently, bands were
      excised, trypsinized, and measured with high-resolution mass spectrometry. We
      sequenced 841 heavy and 771 light chain variable region peptides. We observed 24
      heavy and 26 light chain complementarity determining regions that were solely
      present in a number of multiple sclerosis patients. Using stringent criteria for
      the identification of common peptides, we found five complementarity determining
      regions shared in three or more patients and not in controls. Interestingly, one
      complementarity determining region with a single mutation was found in six
      patients. Additionally, one other patient carrying a similar complementarity
      determining region with another mutation was observed. In addition, we found a
      skew in the kappa-to-lambda ratio and in the usage of certain variable heavy
      regions that was previously observed at the transcriptome level. At the protein
      level, cerebrospinal fluid immunoglobulin G shares common characteristics in the
      antigen binding region among different multiple sclerosis patients. The
      indication of a shared fingerprint may indicate common antigens for B-cell
      activation. 

PMID- 23970566
TI  - Response to Brierley.

PMID- 23970565
TI  - Comparative phosphoproteomics reveals components of host cell invasion and post
      transcriptional regulation during Francisella infection.
AB  - Francisella tularensis is a facultative intracellular bacterium that causes the
      deadly disease tularemia. Most evidence suggests that Francisella is not well
      recognized by the innate immune system that normally leads to cytokine expression
      and cell death. In previous work, we identified new bacterial factors that were
      hyper-cytotoxic to macrophages. Four of the identified hyper-cytotoxic strains
      (lpcC, manB, manC, and kdtA) had an impaired lipopolysaccharide (LPS) synthesis
      and produced an exposed lipid A lacking the O-antigen. These mutants were not
      only hyper-cytotoxic but also were phagocytosed at much higher rates compared
      with the wild type parent strain. To elucidate the cellular signaling underlying
      this enhanced phagocytosis and cell death, we performed a large-scale comparative
      phosphoproteomic analysis of cells infected with wild-type and delta-lpcC F.
      novicida. Our data suggest that not only actin but also intermediate filaments
      and microtubules are important for F. novicida entry into the host cells. In
      addition, we observed differential phosphorylation of tristetraprolin, a key
      component of the mRNA-degrading machinery that controls the expression of a
      variety of genes including many cytokines. Infection with the delta-lpcC mutant
      induced the hyper-phosphorylation and inhibition of tristetraprolin, leading to
      the production of cytokines such as IL-1beta and TNF-alpha that may kill the host
      cells by triggering apoptosis. Together, our data provide new insights for
      Francisella invasion and a post-transcriptional mechanism that prevents the
      expression of host immune response factors that control infection by this
      pathogen. 

PMID- 23970568
TI  - Mass flow and velocity profiles in Neurospora hyphae: partial plug flow dominates
      intra-hyphal transport.
AB  - Movement of nuclei, mitochondria and vacuoles through hyphal trunks of Neurospora
      crassa were vector-mapped using fluorescent markers and green fluorescent protein
      tags. The vectorial movements of all three were strongly correlated, indicating
      the central role of mass (bulk) flow in cytoplasm movements in N. crassa.
      Profiles of velocity versus distance from the hyphal wall did not match the
      parabolic shape predicted by the ideal Hagen-Poiseuille model of flow at low
      Reynolds number. Instead, the profiles were flat, consistent with a model of
      partial plug flow due to the high concentration of organelles in the flowing
      cytosol. The intra-hyphal pressure gradients were manipulated by localized
      external osmotic treatments to demonstrate the dependence of velocity (and
      direction) on pressure gradients within the hyphae. The data support the concept
      that mass transport, driven by pressure gradients, dominates intra-hyphal
      transport. The transport occurs by partial plug flow due to the organelles in the
      cytosol. 

PMID- 23970567
TI  - Multiple rRNA operons are essential for efficient cell growth and sporulation as
      well as outgrowth in Bacillus subtilis.
AB  - The number of copies of rRNA (rrn) operons in a bacterial genome differs greatly
      among bacterial species. Here we examined the phenotypic effects of variations in
      the number of copies of rRNA genes in the genome of Bacillus subtilis by analysis
      of eight mutant strains constructed to carry from two to nine copies of the rrn
      operon. We found that a decrease in the number of copies from ten to one
      increased the doubling time, and decreased the sporulation frequency and
      motility. The maximum levels for transformation activity were similar among the
      strains, although the competence development was significantly delayed in the
      strain with a single rrn operon. Normal sporulation only occurred if more than
      four copies of the rrn operon were present, although ten copies were needed for
      vegetative growth after germination of the spores. This behaviour was seen even
      though the intracellular level of ribosomes was similar among strains with four
      to ten copies of the rrn operon. Furthermore, ten copies of the rrn operon were
      needed for the highest swarming activity. We also constructed 21 strains that
      carried all possible combinations of two copies of the rrn operons, and found
      that these showed a range of growth rates and sporulation frequencies that all
      fell between those recorded for strains with one or three copies of the rrn
      operon. The results suggested that the copy number of the rrn operon has a major
      influence on cellular processes such as growth rate and sporulation frequency. 

PMID- 23970569
TI  - Current treatment methods for combination antiretroviral therapy-induced
      lipoatrophy of the face.
AB  - Combination antiretroviral therapy (CART) reduces the mortality and morbidity in
      HIV-infected patients. However, facial lipoatrophy (FLA) is one of the well-known
      side-effects of this treatment and subsequently imposes major problems for HIV
      infected patients. In the last decade, ample experience has been obtained with
      both local therapeutic options as well as possible systemic treatment options.
      Soft tissue fillers are a relatively simple and efficient treatment option for
      FLA. Especially, the biodegradable semi-permanent fillers combine a good effect
      with durability and an acceptable safety profile. The best way to prevent or
      restrict the development of FLA remains the exclusion of thymidine analogue
      nucleoside reverse-transcriptase inhibitors from the CART schedule. 

PMID- 23970570
TI  - Increasing screening frequency in men who have sex with men: impact of guidance
      on risk profiling on workload and earlier diagnosis of sexually transmitted
      infection and HIV.
AB  - Increasing screening frequency in men who have sex with men (MSM) engaging in
      high-risk behaviours can reduce prevalence of sexually transmitted infections
      (STIs). This evaluation investigated the impact of applying stricter screening
      guidelines for MSM on service workload and earlier STI diagnoses. A validated
      risk assessment tool (RAT) was distributed to MSM attending a level 3 sexual
      health service over three months. Australian screening guidelines were applied to
      the data to identify MSM requiring more frequent screening and data projected to
      the larger MSM population. The RAT identified a 2-5-fold increase in the number
      of STI and HIV screenings required based on six- and three-monthly screening
      intervals, respectively, in the MSM cohort. When screening intervals are reduced
      from three-monthly to six-monthly there is a potential loss of 66.7% of earlier
      HIV diagnoses. The use of RATs will increase workload in sexual health services,
      but potentially diagnose a large proportion of disease earlier.

PMID- 23970572
TI  - Factors associated with asymptomatic non-chlamydial non-gonococcal urethritis in
      heterosexual men: findings from a case-control study.
AB  - The significance of asymptomatic non-chlamydial non-gonococcal urethritis (NCNGU)
      is unclear. Organisms associated with NCNGU, e.g. Mycoplasma genitalium, for
      which there is no widely available test, are linked to reproductive sequelae in
      women but UK guidance no longer recommends urethral smear microscopy to screen
      for asymptomatic NCNGU. This case-control study of heterosexual male
      genitourinary (GU) medicine clinic attenders aimed to identify clinical,
      demographic and sexual behaviour factors associated with asymptomatic NCNGU so
      that we could determine whether the presence or absence of symptoms provides a
      rational basis for deciding to whom we should offer microscopy and whom we should
      treat. Men with asymptomatic NCNGU were very similar to men with symptomatic
      NCNGU, except for more consistent condom use. Asymptomatic and symptomatic NCNGU
      could be different ends of the same clinical syndrome. Until the microbiological
      basis of NCNGU is understood, we recommend treatment of men with NCNGU
      irrespective of symptoms.

PMID- 23970571
TI  - Population-based prevalence of hepatitis B and C virus, HIV, syphilis, gonorrhoea
      and chlamydia in male injection drug users in Lagos, Nigeria.
AB  - There is little research on injecting drug use in Nigeria. We investigated the
      prevalence of HIV, hepatitis B and C, and sexually transmitted infections (STIs)
      among male injection drug users (IDUs) in Lagos. Male IDUs (N = 328) were
      recruited through respondent-driven sampling. Participants completed an interview
      about their sexual and injecting risk behaviours and were tested for hepatitis B
      surface antigen (HBV), hepatitis C antibody (HCV), HIV and syphilis, as well as
      genital chlamydia and gonorrhoea infections. Three-quarters of IDUs (74%)
      reported injecting drugs in the past one month although most did not share
      needles (92%) and the majority obtained sterile needles from pharmacists (87%).
      Estimated HBV, HCV, HIV, syphilis, gonorrhoea and chlamydia prevalences were
      7.8%, 7.7%, 0.9%, 1.9%, 0.0%, and 3.7%, respectively. The burden of HIV is
      presently low among IDUs in Lagos. Changes in accessibility to sterile needles at
      pharmacists would likely have a deleterious effect on IDUs' health. HBV
      vaccination and HCV prevention programmes for IDUs are urgently needed.

PMID- 23970573
TI  - A glimmer of hope? Evaluation of time for non-genitourinary medicine physicians
      to diagnose HIV infection in patients presenting with HIV-related illness.
AB  - A study conducted in 2002-2003 at three UK south coast hospitals measuring the
      length of time for non-genitourinary medicine physicians to diagnose HIV when
      patients presented with an HIV-related illness, found a median time to diagnosis
      of four days with 70% of diagnoses being made within seven days. This
      retrospective cohort study of all patients newly diagnosed with HIV between 1
      January 2010 and 31 December 2011 was conducted at the same three hospitals.
      Thirty-seven patients were newly diagnosed with HIV in non-genitourinary (GU)
      medicine inpatient and outpatient settings (24 men, 13 women), with a mean age of
      43 years. The median time to diagnosis was one day (interquartile range of 0-4
      days), with 81% of diagnoses made within seven days of first presentation. Late
      diagnosis of HIV remains a significant challenge, but delayed diagnosis in a
      patient admitted with an HIV-related illness is reducing in this setting.

PMID- 23970574
TI  - Sharply rising prevalence of HIV infection in Bali: a critical assessment of the
      surveillance data.
AB  - This study critically examines serological survey data for HIV infection in
      selected populations in Bali, Indonesia. Sero-survey data reported by the Bali
      Health Office between 2000 and 2010 were collated, and provincial health staff
      were interviewed to gain a detailed understanding of survey methods. Analysis of
      time series restricted to districts that have used the same sampling methods and
      sites each year indicates that there has been a steady decline in HIV prevalence
      among prisoners, from 18.7% in 2000 to 4.3% in 2010. In contrast, HIV prevalence
      among women engaged in sex work increased sharply: from 0.62% in 2000 to 20.2% in
      2010 (brothel based), and from 0% in 2000 to 7.2% in 2010 (non-brothel based).
      The highest prevalence was recorded among people who injected drugs. Recent
      surveys of gay men and transvestites also found high prevalences, at 18.7% and
      40.9%, respectively. Review of the methodology used in the surveys identified
      inconsistencies in the sampling technique, sample numbers and sites over time,
      and incomplete recording of individual information about survey participants.
      Attention to methodological aspects and incorporation of additional information
      on behavioural factors will ensure that the surveillance system is in the best
      position to support prevention activities.

PMID- 23970575
TI  - Sexual risk and HIV prevention behaviours among African-American and Latino MSM
      social networking users.
AB  - This study explores the feasibility of recruiting minority men who have sex with
      men Facebook users for human immunodeficiency virus (HIV) prevention studies and
      notes demographic and sexual risk behaviours. Facebook-registered men who have
      sex with men (MSM; N = 118) were recruited using online and offline methods.
      Participants validated Facebook-user status through using a Facebook Connect
      (computer science) application. Participants were primarily Latino (60.2%) and
      African-American (28.0%), with 33.1% using social media to find sex partners.
      Black MSM social networking users reported engaging in a lower frequency
      (coefficient = -0.48, p < 0.05) of unprotected receptive anal intercourse
      compared to Latino MSM. Results suggest that minority social media users can be
      recruited for HIV studies and that sexual risk behavioural differences exist
      among minority social networking users. Findings highlight the importance of
      incorporating technologies into population-focused HIV interventions.

PMID- 23970576
TI  - Audit of the effect of electronic patient records on uptake of HIV testing in a
      level 3 genitourinary medicine service.
AB  - This audit aimed to measure the impact of introducing and then modifying an
      electronic patient record (EPR) system on the uptake of HIV testing at a level 3
      genitourinary medicine service. It was a retrospective case note review of all
      new and rebook patients attending our service in 2007 (paper records) and 2010
      (EPR), and a prospective review in 2012 (following modification of the EPR). The
      uptake of HIV testing increased significantly from 72.8% to 78.1% following
      introduction of the EPR (p = 0.009), and increased further to 86.6% (p < 0.0001)
      following modification of the EPR. Clinics using paper notes should consider
      switching to EPR as a means of increasing HIV testing uptake.

PMID- 23970577
TI  - Dilated common bile duct and deranged liver function tests associated with
      ketamine use in two HIV-positive MSM.
AB  - We report here the first two cases of hepatobiliary pathology in HIV-positive men
      following recreational use of ketamine: >1 g/day over a 12-month period while on
      ritonavir-based antiretroviral therapy. Presentation in each case was acute with
      nausea, vomiting and epigastric pain. Alanine aminotransferase was raised at 3.2*
      and 10.1 * upper limit of normal and alkaline phosphatase was raised at 1.7* and
      2.5 * ULN for cases 1 and 2, respectively. Magnetic resonance
      cholangiopancreatography showed dilatation of the common bile duct; case 1, 18 mm
      and case 2, 14 mm with no ductal obstruction on endoscopic retrograde
      cholangiopancreatography. The symptoms resolved, common bile duct dilatation and
      liver function improved on discontinuation of ketamine use. Time to development
      of symptoms is shorter than reported in HIV-negative cases (12 months vs. 4
      years) which may be explained by an interaction between ketamine and ritonavir.

PMID- 23970578
TI  - Endocrine and metabolic abnormalities among HIV-infected patients: a current
      review.
AB  - Multiple endocrine and metabolic abnormalities have been reported among human
      immunodeficiency virus (HIV) patients since the pre-antiretroviral therapy era.
      These abnormalities present with either subclinical or overt clinical features.
      Endocrine and metabolic abnormalities primarily occur due to the direct
      destructive effects of HIV, malignancies and opportunistic infections on the
      varied endocrine glands and antiretroviral therapy-associated toxicities. This
      article offers a broad review on the commonly encountered endocrine and metabolic
      abnormalities among HIV-infected patients. Timely endocrine or metabolic
      evaluations should be performed among patients suspected with endocrine or
      metabolic dysfunction and appropriate treatment instituted since the majority of
      these conditions pose an increased risk of mortality if undiagnosed or untreated.

PMID- 23970579
TI  - Are teachers at higher risk of HIV infection than the general population in
      Burkina Faso?
AB  - In order to assess the human immunodeficiency virus (HIV) prevalence among
      teachers in Burkina Faso, we carried out a national survey in 336 primary and
      secondary schools from urban and rural areas. Among 2088 teachers who agreed to
      participate, 1498 (71.7%) provided urine for HIV testing. The crude prevalence of
      HIV among teachers was 2.8% (95% confidence interval [CI]: 2.0-3.6), with no
      difference between teachers from primary schools (2.9%, 95%CI: 2.1-4.0) and those
      from secondary schools (2.5%, 95%CI: 0.5-4.5). Age- and area-standardized HIV
      prevalence was 1.0% (95%CI: 0.4-1.2) in male teachers, 2.5 times lower than among
      men in the general population (as assessed from a concomitant Demographic Health
      Survey), and it was 3.5% (95%CI: 2.5-5.2) in female teachers, 1.7 times higher
      than in Demographic Health Survey women. This finding calls for the
      implementation of specific HIV prevention programmes in the education sector
      targeting women more specifically.

PMID- 23970580
TI  - Cutaneous candidiasis caused by Candida glabrata in a HIV/AIDS patient.
AB  - Cutaneous Candida infections may occur in patients with HIV/AIDS, cancer,
      receiving chemotherapy and solid organ transplantation. A 32-year-old woman was
      admitted to the department suffering from pruritic and erythematous plaque on
      left side of her face for the past two months. The patient was HIV positive,
      diagnosed five years previously, and had been on antiretroviral therapy
      (tenofovir/emtricitabine and lopinavir/ritonavir) for a year. She was not
      compliant with the medication. Elevated HIV RNA load and decreased CD4+
      lymphocyte count were observed. Fungal elements were detected from the skin
      scraping sample taken from the facial plaque. Fluconazole-sensitive Candida
      glabrata was isolated from this sample. Topical clotrimazole ointment and
      systemic fluconazole 400 mg/day were used. After systemic fluconazole therapy was
      continued for two months, the plaque was cured. C. glabrata rarely causes
      cutaneous infection without involving the mucous membranes. Presentation of
      cutaneous fungal infections in HIV patients with decreased CD4+ T lymphocyte
      counts can be atypical and require extensive antifungal treatment.

PMID- 23970581
TI  - Alcohol and condom use among HIV-positive and HIV-negative female sex workers in
      Nagaland, India.
AB  - This study examines the relationship between alcohol use, HIV status, and condom
      use among female sex workers in Nagaland, India. We analyzed data from a cross
      sectional survey undertaken in 2009, using descriptive and multivariate
      statistics. Out of 417 female sex workers, one-fifth used alcohol daily and one
      tenth were HIV-positive. HIV-positive female sex workers were more likely than
      HIV-negative female sex workers to consume alcohol daily (30.2% vs. 18.0%). HIV
      positive daily alcohol users reported lower condom use at last sex with regular
      clients compared to HIV-positive non-daily alcohol users (46.2% vs. 79.3%), a
      relationship not evident among HIV-negative female sex workers. There is a need
      to promote awareness of synergies between alcohol use and HIV, and to screen for
      problematic alcohol use among female sex workers in order to reduce the spread of
      HIV. 

PMID- 23970582
TI  - Iatrogenic Cushing syndrome after intra-articular triamcinolone in a patient
      receiving ritonavir-boosted darunavir.
AB  - Drug interactions involving human immunodeficiency virus protease inhibitors are
      common due to their inhibition of the cytochrome P450 3A4 isoenzyme. We describe
      the case of an HIV-infected patient treated with ritonavir-boosted darunavir who
      developed cushingoid features following an intra-articular injection of
      triamcinolone acetate. We review the probable mechanism for this interaction and
      describe similar cases of Cushing syndrome in patients receiving concomitant
      ritonavir and triamcinolone. 

PMID- 23970583
TI  - Anal intraepithelial neoplasia: review and recommendations for screening and
      management.
AB  - Anal cancer is a rare malignancy of the distal gastrointestinal tract, often
      associated with human papillomavirus, the most common sexually transmitted
      infection worldwide. Currently available screening methods for anal
      intraepithelial neoplasia, a precursor for anal cancer, combine anal Papanicolaou
      cytology and high resolution anoscopy with biopsy of suspicious lesions.
      Significant barriers to establishing anal cancer screening programmes include the
      small number of healthcare professionals performing high resolution anoscopy and
      the lack of data showing that anal cancer screening can reduce morbidity and
      mortality related to anal carcinoma. Despite several controversies surrounding
      anal cancer screening, the rising incidence of this disease in some groups
      supports routine screening programmes in high-risk populations, especially in HIV
      positive men who have sex with men. This review outlines the epidemiology of anal
      intraepithelial neoplasia and anal cancer and summarizes issues related to the
      introduction of anal cancer screening programmes. 

PMID- 23970585
TI  - Effect of Chlamydia diagnosis on heterosexual relationships.
AB  - This study investigated whether a Chlamydia diagnosis was associated with
      relationship breakup or physical violence from partners when compared to other
      attenders at a sexually transmitted infections (STIs) clinic. Patients diagnosed
      with Chlamydia and who had a regular partner at the time of diagnosis, were
      contacted 3-12 months later and completed a questionnaire on relationship
      history. A comparison group of gender-matched non-STI patients were also
      interviewed. About half of Chlamydia cases (exposed) and non-cases (unexposed)
      had broken up with their partner since diagnosis (52% vs. 47%; p=0.42), but cases
      were more likely to have split up within one week of diagnosis (48% vs. 24%;
      p=0.003), and somewhat more likely to resume the relationship (24% vs. 15%;
      p=0.24). The prevalence of reported physical violence in the past year was
      slightly higher in cases than the unexposed group (9% vs. 4%; p=0.09). Cases that
      saw a health adviser were less likely to report experiencing physical violence
      than those who had not seen a health adviser (7% vs. 12%: p=0.31). Patients with
      Chlamydia are more likely to suffer relationship breakup soon after diagnosis
      than STI clinic attenders without an STI. Health advice should include
      reassurance about sexual relationships as well as safer sex.

PMID- 23970584
TI  - Raltegravir-induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
      syndrome - implications for clinical practice and patient safety.
AB  - This case report describes two severe antiretroviral drug adverse reactions that
      occurred in the same patient. A 55-year-old HIV-positive African woman received a
      single epidural triamcinolone injection for pain relief of postherpetic
      neuralgia. Forty-one days later, she developed severe iatrogenic Cushing's
      syndrome due to the drug-drug interaction between triamcinolone and her boosted
      protease inhibitor therapy. The patient's antiretroviral regimen was thus changed
      to replace her protease inhibitor with the integrase inhibitor raltegravir.
      Shortly after commencing the drug, the patient developed a severe adverse drug
      reaction manifesting as Drug Reaction (or Rash) with Eosinophilia and Systemic
      Symptoms (DRESS) syndrome. First described in 1996, this hypersensitivity
      syndrome presents with severe skin reaction as well as fever, rash,
      lymphadenopathy and internal organ involvement with marked eosinophilia.
      Clinicians should be aware of raltegravir-induced DRESS syndrome as well as the
      potential for drug-drug interactions due to protease inhibitor-based therapy.

PMID- 23970586
TI  - Prevalence and factors associated with erectile dysfunction in a cohort of HIV
      infected patients.
AB  - To determine the prevalence of erectile dysfunction and its associated factors we
      conducted an observational study on a consecutive cohort of asymptomatic HIV
      positive men. All the patients completed a questionnaire to evaluate erectile
      dysfunction based on the International Index of Erectile Function, a validated
      survey for the diagnosis of anxiety and depression (self-administered HAD), and a
      questionnaire about cardiovascular risk factors. Epidemiological, clinical, and
      analytical data were collected. In all, 158 men, participated: mean age 46.0
      years, 96.2% on antiretroviral therapy (91.3% undetectable viral load), and the
      mean CD4 count was 534 cells/mL. Erectile dysfunction was present in 106 (67.1%)
      patients, and associated factors were age (OR 4.5 for each 5 years; 95% CI 4.3
      4.7; p=0.0001) and anxiety (OR 8.2, 95% CI 2.2-30.4; p=0.002). The prevalence of
      erectile dysfunction is high in men living with HIV, even in those with good
      immunovirological control. It is related to increasing age and anxiety, both of
      which are important factors within our HIV cohort.

PMID- 23970587
TI  - Effect of an educational intervention on knowledge, attitudes and preventive
      behaviours related to HIV and sexually transmitted infections in female sex
      workers in southern Iran: a quasi-experimental study.
AB  - This quasi-experimental, before-after study was designed to assess the effect of
      an educational intervention on knowledge and attitudes about sexually transmitted
      infections, HIV and preventive behaviours among female sex workers in Shiraz,
      Iran. A single-group pre-post test design was used and the study was done between
      August and December 2009. The participants were 80 female sex workers recruited
      from three drop-in centers in Shiraz, with stratified random sampling. Pre
      intervention knowledge was assessed by interview with a standard questionnaire.
      The educational intervention consisted of a lecture, face-to-face education,
      printed information, an educational movie, role playing and a contest. After 2
      months, the effect of the intervention was evaluated (post-test). The average age
      of the participants was 32.6 +/- 9.1 years. After the intervention, the mean
      score for general knowledge about HIV and sexually transmitted infections
      increased from 13.7 +/- 0.95 (pre-test) to 19.47 +/- 11.62 (post-test, p<0.001).
      There were significant improvements in attitude and the number of participants
      who self-reported preventive behaviours such as using a condom consistently (from
      45 to 63) (p<0.001). The results show that the educational programme was
      successful in increasing the participants' HIV- and AIDS-related knowledge and
      attitudes, and in decreasing their risk behaviours.

PMID- 23970588
TI  - Sexual risk behaviours and their correlates among gay and non-gay identified men
      who have sex with men and women in Chengdu and Guangzhou, China.
AB  - To better understand the behavioural characteristics and the factors associated
      with high risky behaviours among men who have sex with men and women (MSMW) with
      different orientation, we analyzed data from a cross-sectional survey of 600 MSMW
      in two large cities in China. Participants completed a questionnaire and
      underwent serological testing. Overall, human immunodeficiency virus (HIV)
      prevalence was 26%. In multivariable analysis of risk factors for unprotected
      anal intercourse in the past six months, factors associated with unprotected
      vaginal intercourse (UVI) were as follows: gay-identified orientation, having
      anal sex with a boyfriend, having multiple male partners, and never or sometimes
      using a condom for vaginal intercourse. In multivariate analyses of risk factors
      for UVI in the past 12 months, factors associated with UVI were as follows: non
      gay-identified MSMW, having multiple male partners, having multiple female
      partners, and never or sometimes using a condom for anal intercourse. This study
      revealed a high prevalence of HIV and risky sexual behaviours. 

PMID- 23970589
TI  - Testicular and kidney masses in a HIV-infected man.
AB  - A 37-year-old Caucasian male presented with what appeared clinically and
      diagnostically as testicular and kindey tomour's. However, syphilis serology and
      histology confirm that the lesions were gumma's. Without routine syphilis
      serology, the correct diagnosis may have been missed. 

PMID- 23970590
TI  - Partner-concurrency associated with herpes simplex virus 2 infection in young
      South Africans.
AB  - Whilst much is known about the individual-level risk factors for herpes simplex
      virus 2 (HSV-2) infection, little is known about why only some populations
      develop generalized HSV-2 epidemics. This study aims to assess the extent to
      which partner-concurrency (a factor which operates at both the partnership- and
      network-level) may be responsible. We utilized multivariate logistic regression
      to analyse the relationship between HSV-2 seropositivity and potential risk
      factors in data from a representative cross-sectional survey of 14-24 year olds
      from a township in South Africa conducted in 1999. The overall prevalence of HSV
      2 was 53.3% amongst women and 17% amongst men. For men, four factors remained
      significantly associated with HSV-2 infection in the multivariate regression
      analysis: total number of sex acts, being a migrant labourer, Zulu ethnicity and
      being human immunodeficiency virus (HIV) positive. For women, eight factors were
      associated with HSV-2 infection: increasing age, partner-concurrency (having a
      partner who had other partners), an older partner, total number of sex acts,
      using hormonal contraception, Xhosa ethnicity, syphilis seropositivity and being
      HIV positive. We conclude that partner-concurrency is associated with increased
      HSV-2 seropositivity in women. 

PMID- 23970591
TI  - 2013 UK National Guideline for the management of lymphogranuloma venereum:
      Clinical Effectiveness Group of the British Association for Sexual Health and HIV
      (CEG/BASHH) Guideline development group.

PMID- 23970592
TI  - Avascular necrosis in HIV patients: a case-control study.
AB  - This study investigates the association of avascular necrosis (AVN) in human
      immunodeficiency virus (HIV)-positive individuals with possible risk factors,
      including antiretroviral therapy. Clinic records of all AVN cases diagnosed up to
      July 2009 in HIV-positive patients attending North Middlesex Hospital, London, UK
      were retrospectively reviewed. For each case, one control was randomly selected,
      matched for gender, age, nadir CD4 count and date of HIV diagnosis. Of 15
      symptomatic AVN cases identified, eight were in women. Univariate analysis
      demonstrated significant associations between AVN and a history of systemic
      steroid use (p = 0.004) and cumulative exposure to protease inhibitor (p = 0.03).
      Physicians should be aware of the risk of AVN with steroid use, the importance of
      early diagnosis and avoidance of other risk factors in order to prevent further
      joint involvement if possible.

PMID- 23970593
TI  - Enhanced surveillance of infectious syphilis in New Zealand sexual health
      clinics.
AB  - Following a rise in cases of infectious syphilis in New Zealand, national
      enhanced surveillance at sexual health clinics was initiated. All public sexual
      health clinics reported monthly on the number of cases seen, and completed a
      coded questionnaire on each case. Monthly reports to routine surveillance were
      compared and discrepancies reconciled. During 2011, 72 cases of infectious
      syphilis were reported. The majority (83%) were among men who have sex with men
      who were mainly infected in New Zealand and had an ethnic profile similar to all
      New Zealanders. Most heterosexual infections occurred overseas, among people of
      non-European non-Maori ethnicity. About half the cases had symptoms on
      presentation. Overall, 18% of men who have sex with men were HIV positive.
      Resurgent syphilis in New Zealand disproportionally affects men who have sex with
      men, amongst whom HIV is prevalent. Men who have sex with men should be aware of
      the risks and symptoms of syphilis and encouraged to have regular sexual health
      checks including serology testing. Control of syphilis should be included in the
      strategy to check HIV spread. Syphilis serology should continue to be part of
      routine immigration and antenatal screening, and where clinically indicated.
      Enhanced surveillance was easily initiated for an uncommon condition seen at
      sexual health clinics, and provided valuable information. 

PMID- 23970595
TI  - Liver transplantation for acute liver failure due to efavirenz hepatotoxicity:
      the importance of routine monitoring.
AB  - We present the first case report in the UK of acute liver failure caused by
      efavirenz therapy culminating in liver transplantation. A 26-year-old Zimbabwean
      woman commenced emtricitabine, tenofovir and efavirenz (Atripla) in December
      2011. Her liver function tests at baseline and at 20 days after initiating
      antiretroviral therapy were normal. At three months of therapy her blood tests
      haemolysed and were not processed. She had previously missed follow-up
      appointments and on this occasion failed to return for repeat tests. She was not
      seen again until after six months of antiretroviral therapy when she presented to
      her general practitioner with acute liver failure. Her condition deteriorated and
      she required liver transplantation. She recovered well and re-started
      antiretroviral therapy to good effect. The case illustrates the value of routine
      monitoring after initiating antiretroviral therapy and the fundamental importance
      of engaging patients in long-term management to ensure safe treatment. 

PMID- 23970594
TI  - Characteristics and predictors of women who obtain rescreening for sexually
      transmitted infections using the www.iwantthekit.org screening programme.
AB  - Professional organizations recommend rescreening chlamydia-infected women. The
      iwantthekit Internet-screening programme offered rescreening opportunities by
      using iwantthekit. Mailed, home-collected vaginal swabs were tested for
      chlamydia, gonorrhoea, and trichomoniasis by nucleic acid amplification tests.
      Demographics and risk behaviours of repeat users were determined from
      questionnaires. Predictors of repeat users were measured in a matched case
      control study. Of 1747 women, 304 (17%), who used iwantthekit, indicated they had
      used the kit previously. Mean age was 24.7 +/- 5.7 years and 69% were African
      American. Repeat iwantthekit users were more likely to be aged >= 20 years
      (OR=2.10); were more likely to have been treated for a sexually transmitted
      infection (OR=2.32); less likely to drink alcohol before sex (OR=0.63); and to
      never use condoms (OR=0.43). Of repeat users, 84.2% had a negative prior test and
      15.8% had a positive. At current test, 13.2% were infected. Previous
      trichomoniasis was associated with current trichomoniasis (p<0.05). The
      iwantthekit may offer rescreening opportunities for previously infected women.

PMID- 23970596
TI  - Chest radiographic findings in patients with HIV/AIDS and pulmonary tuberculosis.
AB  - The study describes the main chest radiographic changes in people living with
      HIV/AIDS and pulmonary tuberculosis, confirmed by sputum culture. This was a
      descriptive study involving a total of 42 sputum tests from 42 people living with
      HIV/AIDS and a clinical suspicion of pulmonary tuberculosis. All patients
      attended two referral hospitals in Recife-PE, Brazil, between August 2009 and
      January 2012. The most common isolated radiological change was parenchymal
      consolidation, encountered in six (14.3%) patients, followed by patterns of
      interstitial infiltrate, diffuse micronodular (miliary), and an association
      between interstitial infiltrate and parenchymal consolidation, each being
      encountered in five (11.9%) patients. No statistically significant difference was
      observed between the radiological findings and CD4 T-cell counts, p = 0.680.

PMID- 23970597
TI  - Hepatitis E virus infection in patients infected with human immunodeficiency
      virus in an endemic area in Iran.
AB  - Some studies have suggested that hepatitis E virus is more frequent in human
      immunodeficiency virus (HIV) patients and can progress to chronic infection. We
      aimed to determine the prevalence of hepatitis E virus antibodies and RNA in a
      series of 100 HIV-infected patients in Tehran, Iran, with comparison to 52
      healthy HIV, hepatitis B and C-negative blood donors as controls. HIV-infected
      patients were also tested for hepatitis E virus-RNA. Among the HIV-infected
      patients, 10% had antibodies to hepatitis E virus - a finding not significantly
      different from the uninfected controls (11.5%). No HIV-infected patients had
      hepatitis E virus IgM antibodies nor did any have detectable hepatitis E virus
      RNA. We found no associations between anti-hepatitis E virus IgG-seropositivity
      and age, sex, route of HIV acquisition, aminotransferases levels, CD4,
      antiretroviral therapy, hepatitis B virus and hepatitis C virus co-infection.
      Hepatitis E virus is relatively prevalent in our HIV-infected patients, although
      without evidence of chronic infection and no more common than among HIV-negative
      controls or the general population. For the present, we do not recommend routine
      screening for hepatitis E virus infection in HIV-infected patients in our
      moderately endemic region. 

PMID- 23970598
TI  - Improving clinical governance of HIV treatment programmes in resource poor
      settings: the role of digitising clinical notes.
AB  - Implementing clinical audit in a resource poor setting is often beset by
      practical issues. Out-sourcing the burden of data analysis may go a long way to
      facilitating regular audit in a resource poor setting. We investigated the
      feasibility of using an inexpensive 12-megapixel point-and-shoot digital camera
      to collect data from clinical notes in a format capable of being sent via secure
      electronic file transfer for remote analysis. We then performed a pilot audit on
      this data as a proof of principle. 

PMID- 23970600
TI  - Development of a young persons' HIV clinic in a District General Hospital: a case
      note review resulting in informed change.
AB  - In recognition of the increasing number of HIV-infected young people attending
      the HIV department at a district general hospital, a case note review was
      conducted. There was a high prevalence of psychosocial problems and medical
      complexity among this cohort. As a result, tailored young persons' services were
      developed. Effective utilisation of the existing skill-mix and resources were key
      to success. 

PMID- 23970599
TI  - Factors associated with condom use negotiation by female sex workers in
      Bangladesh.
AB  - Negotiation for condom use by female sex workers with their male clients can
      enhance condom use. A cross-sectional study was conducted among 1395 female sex
      workers; 439 from two brothels, 442 from 30 hotels, and 514 from streets of two
      cities in Bangladesh to determine the predictors of condom use negotiation.
      Consistent condom use rates in the 7 days prior to interview were reported to be
      16.2%, 21.7%, and 4.5% among the brothel, hotel, and street-based female sex
      workers, respectively. Overall, 28.1% of female sex workers negotiated for condom
      use with their clients. Participation in behaviour change communication (BCC)
      programmes (AOR, 1.5; 95% CI, 1.2-2.0) and self-perceived risk of human
      immunodeficiency virus infection (AOR, 1.8 95% CI, 1.6-2.1) were positive
      predictors for condom negotiation. Compared to the hotel-based female sex
      workers, street (AOR, 0.6; 95% CI, 0.4-0.9) and brothel-based female sex workers
      (AOR, 0.7; 95% CI, 0.5-0.9) were less likely to negotiate for condom use. Female
      sex workers in Bangladesh are at high risk for sexually transmitted infection /
      human immunodeficiency virus infection because of low overall negotiation for
      condom use. Participation in BCC programmes had positive effect on condom
      negotiation by female sex workers, and should be strengthened in commercial sex
      venues. 

PMID- 23970601
TI  - Health-related quality of life of HIV-infected intravenous drug users.
AB  - To investigate health-related quality of life in HIV-infected intravenous drug
      users registered but not engaged in HIV outpatient care (missing >=2 outpatient
      appointments over 1 year or non-attendance for >=6 months) we conducted a cross
      sectional study to examine health-related quality of life of HIV-infected
      intravenous drug users registered for care at an inner city HIV unit. EQ-5D, SF
      36, SF-6D, mood disorder, clinical and substance misuse data were collected. Mean
      scores and preference derived utility scores were calculated. Statistical
      relationships between health-related quality of life and other variables were
      explored using univariate and multivariate analysis. Fifty-five patients were
      recruited, 64% were males. The mean anxiety value was 11.44 (anxious) and mean
      depression score was 9.3 (borderline depressed). The mean EQ-5D utility was 0.45
      (95% CI 0.35, 0.55) and mean SF-6D utility was 0.52 (95% CI 0.48, 0.55). There
      was no statistical relationship between HIV indices, substance misuse and EQ-5D
      and SF-6D utility. Anxiety and depression were significantly correlated with EQ
      5D and SF-6D utility values on univariate and multivariate analysis. Health
      related quality of life was reduced in this HIV-infected intravenous drug user
      population. Whilst hepatitis C co-infection and substance misuse did not affect
      health-related quality of life, anxiety and depression had a significant impact
      on it. 

PMID- 23970602
TI  - Prevalence of pharyngeal infection by Neisseria gonorrhoeae among human
      immunodeficiency virus-positive men who have sex with men in downtown Madrid,
      2011.
AB  - The prevalence of pharyngeal gonorrhoea in human immunodeficiency virus (HIV)
      positive men who have sex with men (MSM) is not entirely known. We cultured the
      pharynx of 264 asymptomatic HIV-positive MSM in downtown Madrid. A questionnaire
      on sexual and drug use risk behaviours was also administered. Gonococci were
      isolated in 25 (9.5%). Among the whole study population, 65% had a history of
      sexual intercourse with two or more partners on a single day and 26% were
      involved in group sex with other men. Only 29% regularly used condoms in all
      sexual encounters and 63% used condoms only in insertive anal intercourse. When
      asked about oral sex, 89% of patients engaged in insertive and/or receptive oral
      sex and 86% recognized that they did not regularly request the use of condoms
      when practising "fellatio" on a partner. Cocaine, crystal methamphetamine or
      alcohol use and a previous history of >=1 sexually transmitted infection were
      significantly more common among culture-positive patients. Gonococcal
      colonization of the pharynx was self-limited in patients that were not treated
      and re-cultured a mean 18.5 +/- 5.2 days after diagnosis. Asymptomatic pharyngeal
      gonorrhoea is common among HIV-positive MSM and may contribute to the increasing
      epidemic of gonorrhoea in Madrid. 

PMID- 23970603
TI  - Circumcision as treatment for Zoon's balanitis in an HIV-positive teenage
      patient.
AB  - In this report we describe a case of the Zoon's balanitis in a boy with HIV (AIDS
      B2). The clinical presentation, failure of topical treatment, cure by
      circumcision, and the histopathology findings are presented. 

PMID- 23970604
TI  - Survival rate of AIDS disease and mortality in HIV-infected patients in Hamadan,
      Iran: a registry-based retrospective cohort study (1997-2011).
AB  - There remains a need to better understand the prognostic factors affecting the
      long-term survival in patients with human immunodeficiency virus (HIV)/acquired
      immunodeficiency syndrome (AIDS), particularly in developing countries. We
      extracted data from 585 patients' medical records available at the triangular
      clinics for behavioural diseases. The outcomes of interest were the survival
      rates of progression to AIDS and death in HIV-positive subjects. The effect of
      several prognostic factors on survival time was investigated. One-year, five-year
      and 10-year survival rates from time of HIV diagnosis to AIDS were 89%, 69% and
      30%, respectively. One-year and five-year survival rates from AIDS to death were
      76% and 46%, respectively. One-year, five-year and 10-year survival rate from HIV
      diagnosis to death were 87%, 67% and 40%, respectively. Hazard ratio of
      progression to AIDS in HIV-positive subjects who were co-infected with
      tuberculosis was 4.50 (p < 0.001). Hazard ratio of death from AIDS-related causes
      was 4.77 in patients who did not receive highly active antiretroviral therapy
      compared to those who did (p < 0.001). Co-infection with tuberculosis was one of
      the most important prognostic factors of progression to AIDS and antiretroviral
      treatment was found to be an effective measure in suppressing HIV viral
      replication and improving the survival of patients living with HIV. 

PMID- 23970605
TI  - Vulval disease in HIV-positive women attending a tertiary vulval dermatology
      clinic over a five-year period.
AB  - There is a paucity of data on vulval disease in HIV-infected women. We describe
      the spectrum of vulval disease in HIV-infected women attending a tertiary vulval
      dermatology referral centre over a five-year period. Seven vulval conditions were
      identified in 14 women. Most were attending for HIV care (n = 12, 86%), and on
      combined antiretroviral therapy (CART) with a CD4 cell count above 200 cells/uL
      (n = 9, 64%) at diagnosis. Imiquimod therapy was effective in treating
      undifferentiated vulval intraepithelial neoplasia (uVIN) - the most common
      diagnosis. There were no cases of invasive vulval carcinoma. Hypertrophic herpes
      simplex virus occurred in one woman stable on CART with good immune
      reconstitution. Clinicians should be vigilant about the spectrum of vulval
      disease in HIV-infected women and consider genital examination as part of routine
      care.

PMID- 23970606
TI  - Comparison of two interferon-gamma release assays (QuantiFERON-TB Gold In-Tube
      and T-SPOT.TB) in testing for latent tuberculosis infection among HIV-infected
      adults.
AB  - There is currently no 'gold standard' for diagnosis of latent tuberculosis
      infection (LTBI), and both the tuberculin skin test and interferon-gamma release
      assays (IGRAs) are used for diagnosis; the latter have a higher sensitivity than
      tuberculin skin tests for diagnosis of LTBI in HIV-infected individuals with
      lower CD4 counts. No evidence base exists for selection of IGRA methodology to
      identify LTBI among human immunodeficiency virus-infected patients in the UK. We
      prospectively evaluated two commercially available IGRA methods (QuantiFERON-TB
      Gold In Tube [QFG] and T-SPOT.TB) for testing LTBI among HIV-infected patients
      potentially nosocomially exposed to an HIV-infected patient with 'smear-positive'
      pulmonary tuberculosis. Among the exposed patients median CD4 count was 550
      cells/uL; 105 (90%) of 117 were receiving antiretroviral therapy, of who 104
      (99%) had an undetectable plasma HIV load. IGRAs were positive in 12 patients
      (10.3%); QFG positive in 11 (9.4%) and T-SPOT.TB positive in six (5.1%); both
      IGRAs were positive in five patients (4.3%). There was one indeterminate QFG and
      one borderline T-SPOT.TB result. Concordance between the two IGRAs was moderate
      (kappa = 0.56, 95% confidence interval = 0.27-0.85). IGRAs were positive in only
      4 (29%) of 14 patients with previous culture-proven tuberculosis. No patient
      developed tuberculosis during 20 months of follow-up.

PMID- 23970607
TI  - Trichomonas vaginalis: an audit of clinical practice and the demography of
      infected patients at three London genitourinary medicine clinics.
AB  - This audit aimed to review clinical standards for Trichomonas vaginalis against
      British Association of Sexual Health and HIV (BASHH) guidelines. Case notes for
      patients who had a positive microscopy or culture result were reviewed
      retrospectively. There was a 0.23% positivity rate for T. vaginalis (n = 84
      cases); 96% were female with an average age of 33 years, with proportionally more
      patients seen in the African/Caribbean population, despite the number of cases
      being comparable between white (n = 36) and African/Caribbean (n = 34) groups.
      Seventy percent of patients had both microscopy- and culture-positive results for
      T. vaginalis. Contact tracing occurred in 87% of patients; 56% of these patients
      confirmed at least one contact had been treated in the last month. Overall, our
      data demonstrated a lower positivity rate than expected. Wet microscopy and
      liquid medium cultures were both important in identifying the infection, but more
      needs to be done to ensure partner notification has been documented and contacts
      have been treated. 

PMID- 23970608
TI  - Size of anal squamous cell carcinomas at diagnosis: a retrospective case series.
AB  - Anal squamous cell carcinoma is more common in HIV-positive homosexual men than
      in the general population and prognosis worsens with increasing tumour size. To
      identify opportunities for earlier diagnosis, we aimed to determine size and
      visibility of anal squamous cell carcinoma at diagnosis. We conducted a
      retrospective review of medical records between 1992 and 2010 from one hospital
      radiotherapy centre, a major centre for HIV care, in Melbourne, Australia. Of 128
      cases of anal squamous cell carcinoma, 24 (19%) were in HIV-positive men. At
      diagnosis, half (52%) of the tumours were externally visible and mean estimated
      tumour size was 36 mm (29 mm in HIV-positive and 38 mm in HIV-negative patients;
      p = 0.04) and 114/121 (94%) tumours were 1 cm or larger. The most frequent
      symptoms were bleeding (43%) and pain (36%) and mean duration of symptoms was 22
      weeks. This suggests most anal squamous cell carcinoma were visible or palpable
      for some time before diagnosis, meaning that screening high-risk groups by anal
      inspection and palpation is plausible. 

PMID- 23970609
TI  - Condom use behaviours and correlates of use in the Botswana Defence Force.
AB  - Preventing HIV infection is a priority for militaries. HIV prevention research is
      needed to monitor existing programme, identify areas for modification, and
      develop new interventions. Correct and consistent condom use is highly effective
      against HIV. However, use among soldiers is lower than ideal. This study
      describes condom use behaviours and examines correlates of use in the Botswana
      Defence Force (BDF). Analyses were based on 211 male BDF personnel, aged 18-30,
      who completed a cross-sectional survey that collected baseline data for an
      intervention study. Results showed that 51% of participants reported always using
      condoms, 35% used condoms most times, and 14% used condoms occasionally/never.
      Condom use varied by partner type and was typically higher with casual partners
      in comparison to regular partners. After adjustment for age and marital status,
      factors associated with lower condom use included excessive alcohol use,
      perception that using condoms reduce sexual pleasure, and having a trusted
      partner. However, higher levels of HIV knowledge and reports of being circumcised
      were protective against lower condom use. HIV interventions aimed at increasing
      condom use in the BDF should address condom perceptions, alcohol abuse, and
      issues of trust. Innovative ways to increase condom use in this population should
      also be explored. 

PMID- 23970610
TI  - Use of tablet-based kiosks in the emergency department to guide patient HIV self
      testing with a point-of-care oral fluid test.
AB  - Despite successes in efforts to integrate HIV testing into routine care in
      emergency departments, challenges remain. Kiosk-facilitated, directed HIV self
      testing offers one novel approach to address logistical challenges. Emergency
      department patients, 18-64 years, were recruited to evaluate use of tablet-based
      kiosks to guide patients to conduct their own point-of-care HIV tests followed by
      standard-of-care HIV tests by healthcare workers. Both tests were OraQuick
      Advance tests. Of 955 patients approached, 473 (49.5%) consented; 467 completed
      the test, and 100% had concordant results with healthcare workers. Median age was
      41 years, 59.6% were female, 74.8% were African-American, and 19.6% were White.
      In all, 99.8% of patients believed the self-test was "definitely" or "probably"
      correct; 91.7% of patients "trusted their results very much"; 99.8% reported
      "overall" self-testing was "easy or somewhat easy" to perform. Further, 96.9%
      indicated they would "probably" or "definitely" test themselves at home were the
      HIV test available for purchase; 25.9% preferred self-testing versus 34.4% who
      preferred healthcare professional testing (p>0.05). Tablet-based kiosk testing
      proved to be highly feasible, acceptable, and an accurate method of conducting
      rapid HIV self-testing in this study; however, rates of engagement were moderate.
      More research will be required to ascertain barriers to increased engagement for
      self-testing.

PMID- 23970611
TI  - Human papillomavirus-associated balanoposthitis--a marker for penile
      intraepithelial neoplasia?
AB  - The purpose of this study was to analyse, among men treated with diathermy,
      whether there was a difference in balanoposthitis between men with
      histopathologically benign human papillomavirus-associated lesions and those with
      penile intraepithelial neoplasia. Data were derived from patient material from a
      previously published study. Two clinically identical lesions from the same
      genital site were collected for analysis with routine histopathology and with
      nested PCR. In total, 292 men were included, of which 47 (16%) had penile
      intraepithelial neoplasia. Of those with penile intraepithelial neoplasia, 19/47
      (40%) reported problems consistent with balanoposthitis, compared with only
      15/245 (6%) patients with benign lesions (p < 0.0001). A statistical difference
      in percentage distribution was also seen regarding morphology (p = 0.001) and
      location (p = 0.0003) of the lesions among the men having benign lesions with and
      without balanoposthitis. It is not possible to take biopsies from patients with
      genital warts, but this study suggests that one probably should be more observant
      for genital dysplasia among those men with warts with a history of
      balanoposthitis than those with no such history.

PMID- 23970612
TI  - An unusual case of hyperlactataemia in a neonate.
AB  - We report a HIV uninfected neonate born to HIV positive mother, who had
      tachypnoea at birth. On investigations, he was found to have hyperlactataemia.
      All the secondary causes for elevated lactate were ruled out. Hyperlactataemia
      was attributed to the perinatal exposure, to maternal antiretroviral (ARV) drugs,
      mainly nucleoside analogues. Asymptomatic and symptomatic hyperlactataemia is not
      uncommon in HIV-exposed infants. Neonates with tachypnoea, who are HIV- and ARV
      exposed with no obvious cause, should be screened for raised arterial lactate. 

PMID- 23970613
TI  - Multiple self-report measures of antiretroviral adherence correlated in Sierra
      Leone, but did they agree?
AB  - In resource-poor settings, studies validating multiple self-report measures of
      adherence are limited and do not include data from West Africa. We prospectively
      assessed the associations between multiple self-report measures of adherence in
      58 patients receiving antiretroviral therapy. Self-report measures included a 30
      day visual analog scale, 30-day qualitative single-item measure, Adult AIDS
      Clinical Trial Group 4-day recall, and 3-level categorical 7-day qualitative
      measure. Unannounced pill count was the objective measure. Spearman's rho
      correlation coefficients, Bland-Altman plots, and receiver operator curve
      analyses were performed. Median and mean adherence by pill count were 81.8% and
      78.6%, respectively. All self-report measures had either intermediate or high
      correlation with the pill count, and the 7-day measure had the highest level of
      correlation with pill count (r = 0.72). All self-report measures demonstrated
      good agreement when mean pill count adherence was greater than 90%. All but the 7
      day measure posed challenges to patient understanding and administration of the
      measure. In this sample of participants that displayed largely suboptimal
      adherence, the 7-day measure was preferable, but all self-report measures
      demonstrated relatively good agreement with the objective criterion pill count
      measure and are adequate for clinical use in settings such as Sierra Leone.

PMID- 23970614
TI  - An unusual cause of persistent postpartum vaginal discharge.
AB  - We describe the case of a 27-year-old woman with a three-month history of
      persistent green vaginal discharge following vaginal delivery of her first child.
      Group C beta-haemolytic streptococcus was ultimately isolated, which appears to
      be an uncommon cause of this clinical presentation. 

PMID- 23970615
TI  - Daily dose of clindamycin versus standard divided doses in obstetrical and
      gynecological infections: a retrospective cohort study.
AB  - To compare the rates of cure of septic abortion and pelvic inflammatory disease
      using a daily dose of clindamycin with gentamicin versus divided doses, we
      conducted a retrospective cohort study, where the electronic records of 661
      patients who used clindamycin 1 * , 3 * or 4 */day (groups 1, 3 and 4,
      respectively) between September 2002 and August 2010 were analysed. Major
      outcomes included rates of cure and failure according to the clinical records.
      Secondary endpoints were percentage of adverse effects related to medication
      regimen and the prevalence of positive VDRL and HIV. Similar conditions were
      observed in all groups - septic abortion: 167/116/123; pelvic inflammatory
      disease: 73/95/87 (groups 1, 3 and 4, respectively). No significant difference
      was found among groups for age or for rate of cure. Rates of cure (cure/total
      [rate (95%CI)]) in groups 1, 3 and 4 were 236/240 [0.983 (0.957-0.993)], 205/211
      [0.971 (0.939-0.986)], 203/210 [0.966 (0.932-0.983)], respectively. Days of use
      of clindamycin was significantly reduced in group 1, compared to groups 3 and 4
      (2.6 +/- 1.3 vs. 3.5 +/- 2.5 vs. 3.3 +/- 1.9-mean +/- SD; p < 0.0001 - ANOVA),
      but this may be due to differences in how length of therapy was measured and not
      the effect on clinical cure. 

PMID- 23970616
TI  - Recurrent lower gastrointestinal bleeding due to primary colonic Kaposi's sarcoma
      in a patient with AIDS.
AB  - Epidemic Kaposi's sarcoma remains the most common cancer in patients with human
      immunodeficiency virus and is associated with significant morbidity and mortality
      in AIDS patients. Primary visceral Kaposi's sarcoma (Kaposi's sarcoma without
      cutaneous lesions) presenting with lower gastrointestinal bleeding (LGIB) has
      rarely been reported. Though Kaposi's sarcoma can occur anywhere in
      gastrointestinal tract, gastrointestinal symptoms are often non-specific such as
      chronic blood loss anaemia, vomiting, diarrhoea, intestinal obstruction. In these
      patients, severe gastrointestinal bleeding requiring repeated blood transfusions
      is extremely rare. Clinicians should be aware of gastrointestinal tract Kaposi's
      sarcoma since visceral Kaposi's sarcoma can present in the absence of cutaneous
      involvement. Endoscopy with biopsy is useful in the diagnosis for severe LGIB in
      patients with AIDS. Furthermore, gastrointestinal Kaposi's sarcoma should be
      considered in the differential diagnosis of GI bleeding. We report a case of
      primary colonic KS who presented with recurrent GI bleeding which was eventually
      diagnosed by sigmoidoscopy and confirmed pathologically. 

PMID- 23970617
TI  - Atraumatic splenic rupture secondary to chronic HIV infection.
AB  - As patients infected with HIV live longer due to effective anti-retroviral
      therapy, new disease manifestations are becoming apparent. We describe the case
      of a 59-year-old patient who presented to our unit with atraumatic splenic
      rupture secondary to chronic HIV infection. Given the high mortality associated
      with atraumatic splenic rupture, we believe it should be included in the
      differential diagnosis of HIV-positive patients presenting with acute abdominal
      pain. 

PMID- 23970618
TI  - Invasive trichosporonosis in an AIDS patient: case report and review of the
      literature.
AB  - Invasive Trichosporon infection is a rare, life-threatening infection in
      immunocompromised patients. It has been reported as an emerging opportunistic
      infection in those with acquired immune deficiency syndrome (AIDS). Only 12 cases
      of invasive trichosporonosis in patients with HIV have been documented, none in
      Southeast Asia. We report a case of fatal, disseminated trichosporonosis in a
      Filipino AIDS patient with severe cutaneous and pulmonary involvement. Invasive
      trichosporonosis should be considered in HIV-positive patients with disseminated
      fungal infection since this may be refractory to conventional antifungal
      treatment. 

PMID- 23970620
TI  - Persistent genital arousal and restless genitalia: sexual dysfunction or subtype
      of vulvodynia?
AB  - We conducted a literature review of patients' conditions described under
      persistent genital arousal disorder and restless genital syndrome, vulvodynia and
      male genital skin pain of unknown aetiology (penoscrotodynia). Our aim is to
      improve the understanding of the condition, unify nomenclature and promote
      evidence-based practice. The most prominent symptom in persistent genital arousal
      disorder and restless genital syndrome is a spontaneous, unwelcomed, intrusive
      and distressing vulval sensation. There are similarities between the clinical
      presentation of vulvodynia, penoscrotodynia, persistent genital arousal disorder
      and restless genital syndrome patients. The aetiology of persistent genital
      arousal disorder and restless genital syndrome, similar to vulvodynia, could be
      better explained in terms of neuro-vascular dysfunction, genital peripheral
      neuropathy and/or dysfunctional micro-vascular arterio-venous shunting.
      Erythromelalgia lends itself to explain some cases of restless genital syndrome,
      who have concurrent restless legs syndrome; and therefore draw parallels with the
      red scrotum syndrome. The published literature supports the concept of
      classifying restless genital syndrome as a sub-type of vulvodynia rather than
      sexual dysfunction. 

PMID- 23970619
TI  - Epidemiologic correlates of willingness to be tested for HIV and prior testing
      among married men in India.
AB  - There has been limited research in India on determinants of seeking HIV testing
      by Indian married couples. We analyzed data obtained from husbands of married
      couples participating in the National Family Health Survey 2005-06. Socio
      demographic and behavioural predictors for willingness to be tested and self
      reported prior testing were explored, using multivariate logistic regression.
      Factor scores were used to summarize knowledge variables related to HIV
      prevention and places of testing. Sixty-nine percent of the husbands were willing
      to be tested as part of National Family Health Survey 2005-06, and 7% reported
      some form of prior testing. Our results indicate that knowledge about HIV testing
      in hospitals and other health/welfare centres, knowledge about transmission of
      HIV, poor education, religion, economic status, occupation, early sexual debut,
      and use of contraceptives other than barrier methods were significant predictors
      for reported willingness to be tested. Knowledge about routes of transmission of
      HIV, younger age, educational level, religion other than Hindu or Muslim,
      economic status, occupation, history of blood transfusion, and condom use were
      significant correlates of previously being tested. Strategies to improve
      knowledge about HIV testing sites and HIV prevention may encourage married men to
      be tested and reduce the spread of infection from them to their wives. 

PMID- 23970621
TI  - Asymptomatic syphilitic massive necrosis of the spleen in late syphilis.
AB  - The varieties of luetic clinical variants are countless in nature. In this
      regard, an autopsy case of a 72-year-old homeless man who accidentally succumbed
      to carbon-monoxide poisoning is here presented and reviewed. The autopsy revealed
      the highly unusual finding of asymptomatic syphilitic necrosis of spleen followed
      by luetic mesaortitis, a solitary skin gumma, and syphilitic arthritis. The
      spleen was 8*4*3 cm in size; the capsule was completely calcified and firm, 3 to
      5 mm thick. Only in the region of the hilus was a small part of preserved tissue
      found. After puncturing the capsule, a brown-yellowish pus-like mass was found
      which filled the entire space inside. When reviewing the relevant literature,
      this case and its finding of pan splenic necrosis accompanied by a calcified
      capsule seem to be unique in nature. In terms of the final diagnosis, a Treponema
      pallidum haemagglutination assay confirmed it to be syphilis. Since it was a late
      stage of the disease, it is estimated that it may have been present for more than
      20 or 30 years in the deceased.

PMID- 23970622
TI  - Associations between drug use and sexual risks among heterosexual men in the
      Philippines.
AB  - The relationship between drug use and sexual risk behaviours among 2272 men in
      the southern Philippines was assessed. Over 20% of participants used drugs.
      Logistic regression analyses adjusted for age, marital status, income, occupation
      and geographic region revealed that compared to non-drug users, men who used
      drugs had earlier sexual debuts (adjusted odds ratio = 1.73; 95% confidence
      interval = 1.38-2.17), were more likely to report two or more recent sexual
      partners (adjusted odds ratio = 2.22; 95% confidence interval = 1.59-3.11), and
      were more likely to report ever having sex with a female sex worker (adjusted
      odds ratio = 2.99; 95% confidence interval = 2.25-4.00). Condom use was noted to
      be low overall among the men in this study; however, the odds of more frequent
      condom use with a regular partner were greater for men who used drugs compared to
      non-drug users (adjusted odds ratio = 1.60; 95% confidence interval = 1.26-2.02).
      There were no significant differences in condom use during last sex or frequency
      of condom use with a sex worker. While injection drug use was not common (1%),
      use of oral or inhaled substances was prevalent, and associated with increased
      sexual risk for acquisition and transmission of STI/HIV. Efforts to decrease
      STI/HIV transmission should specifically target non-injection drug use as a risk
      factor.

PMID- 23970623
TI  - High syphilis but low HIV prevalence rates among pregnant women in New Caledonia.
AB  - Sexually transmitted infections have been described as one of the major health
      problems in several countries of the Pacific Region. The objective of the study
      was to estimate the prevalence of pregnant women infected with HIV and/or
      syphilis in New Caledonia. HIV and syphilis test results were obtained from women
      attending antenatal clinics. From 2008 to 2011, 3353 pregnant women were tested
      with a mean prevalence of active syphilis found at 5.6/100,000. No pregnant women
      tested positive for HIV. Despite available resources and public health strategies
      similar to those existing in France, active syphilis prevalence is high in New
      Caledonia. Surprisingly, HIV seroprevalence remains far below the figures
      reported in mainland countries. However, social and economic changes as well as
      the looming referendum on independence scheduled in 2014 may have a potential
      negative impact on public health resources. The need for action to control
      syphilis and other curable sexually transmitted infections is pressing in order
      to prevent further spread of HIV in New Caledonia. 

PMID- 23970624
TI  - Pustulosis acuta generalisata following chemotherapy in an HIV-positive patient.
AB  - Pustulosis acuta generalisata is an uncommon condition characterized by scattered
      symmetrical eruption of sterile pustules associated with elevated inflammatory
      markers, leukocytosis, fever and arthropathy caused by previous infection by
      group A streptococci (GAS). We reported here a case of pustulosis acuta
      generalisata in an HIV-positive patient recently treated with chemotherapy for a
      seminoma. 

PMID- 23970625
TI  - Isolated pharyngeal Neisseria gonorrhoeae in heterosexual male contacts.
AB  - Pharyngeal infection with Neisseria gonorrhoeae (NG) in heterosexual men is
      thought to be of low prevalence and the value of routinely testing this group of
      patients is uncertain. We present two cases of NG, isolated only in the pharynx,
      in asymptomatic heterosexual male contacts. The presence of pharyngeal NG was
      found irrespective of direct oropharyngeal sexual exposure. 

PMID- 23970626
TI  - Comparing the performance of traditional non-treponemal tests on syphilis and non
      syphilis serum samples.
AB  - The goal of the present study was to determine the performance of two traditional
      non-treponemal tests for syphilis. Syphilis sera (n = 209) included different
      stages of disease, and control sera (n = 247) were from patients with tumours,
      leprosy, systemic lupus erythematosus, hepatitis, pregnant women and healthy
      individuals. Treponema pallidum ELISA, Treponema pallidum particle agglutination
      and rapid treponema-specific tests were used as gold standards. Rapid plasma
      reagin or toluidine red unheated serum test had a sensitivity and specificity of
      over 95%. False-negative reactions of rapid plasma reagin and toluidine red
      unheated serum test were observed mainly in primary and latent syphilis cases,
      and false-positive reactions were present in systemic lupus erythematosus,
      hepatitis-infected patients. Overall, both non-treponemal tests had high
      sensitivities and specificities making the assays attractive as screening tests
      for syphilis. When examined on WHO reference serum samples and based on lower
      limits of detection, non-treponemal tests were less sensitive than treponema
      specific tests.

PMID- 23970627
TI  - Comparison of risk factors for prevalent sexually transmitted infections based on
      attendees at two genitourinary medicine clinics in Ireland.
AB  - Little has changed in sexually transmitted infection (STI) epidemiology in
      Ireland since 2000. Three STIs comprise approximately 90% of notifications; ano
      genital warts, Chlamydia trachomatis and non-specific urethritis. Our objective
      was to compare the risk factors for prevalent STIs in attendees at two
      genitourinary medicine clinics and examine the incidence of coinfection.
      Diagnostic, demographic and behavioural information on attendees at two clinics
      in southwest Ireland were collected from January 1999 to July 2009. Risk factors
      associated with first episodes of ano-genital warts, genital herpes simplex viral
      infection, non-specific urethritis and C. trachomatis were investigated. In all,
      22,705 STI patients (mean age 27 years) received 26,824 diagnoses; 1628 had more
      than one infection. Ano-genital warts was most likely to be diagnosed with a
      coinfection. Having multiple partners was positively associated with a diagnosis
      of bacterial infection but not viral infection. Our large cohort outlines those
      at risk in the region, showing age and gender influences the risk and type of
      infection. Smoking, alcohol and drug use is also common, all regarded as markers
      of risk-taking behaviour. The younger the age, the higher the risk of acquiring
      infection, regardless of infection type. Prevention strategies that target youth,
      bacterial STIs and high-risk behaviour, including sexual, alcohol and drugs, may
      be effective in reducing STI incidence in Ireland. 

PMID- 23970628
TI  - Early loss to follow-up and mortality of HIV-infected patients diagnosed after
      the era of antiretroviral treatment scale up: a call for re-invigorating the
      response in Iran.
AB  - In Iran, the HIV/AIDS epidemic is growing during an era of scaling up the
      national surveillance system and antiretroviral therapy programs. We examined the
      early loss to follow-up and mortality rates in a retrospective cohort of 1495 HIV
      infected patients by survival proportional hazard Cox model. We also conducted a
      data abstraction sub-study in a systematic random sample of 147 patients to
      assess the association between mortality and predictor factors. Overall, 17.3%
      patients were not seen after their first visit and 17.4% more were lost by 6
      months. The overall mortality rate was 7.0 (95% CI 6.1-8.1) per 100 person-years.
      Moreover, crude mortality rate was higher in men (8.6) than in women (1.7), with
      an age-adjusted hazard ratio for men compared to women of 4.55 (95% CI 2.31
      8.93). Lastly, history of tuberculosis and not being on antiretroviral therapy
      were significantly associated with higher mortality in the patient sub-sample. 

PMID- 23970629
TI  - Post-exposure prophylaxis after sexual exposure (PEPSE) awareness in an HIV
      positive cohort.
AB  - Post-exposure prophylaxis after sexual exposure (PEPSE) awareness was audited in
      an HIV-positive cohort. A total of 403 out of 828 (48.7%) patients were PEPSE
      aware. Patients diagnosed post-2006 were more PEPSE aware; 57.2% vs. 44.2% (p =
      0.0004). Men who have sex with men (MSM) were more PEPSE aware; 65.8% vs. 39.1%
      in heterosexuals (p < 0.0001).Younger patients, 68.1% aged 19-34 were PEPSE aware
      vs. 45.7% in those >35 years (p < 0.0001). In the 534 patients reporting sexual
      activity within the last year, awareness was 57.5%. In the 216 patients
      'sometimes' or 'never' using condoms, awareness was 42.6%. In the 78 (9.4%)
      patients with detectable viral loads (>400 copies/mL), awareness was 64.1%.
      Overall, PEPSE awareness was unexpectedly low. MSM, younger patients, and those
      diagnosed after 2006 were significantly more likely to be PEPSE aware. More than
      one in three patients with detectable viraemia were PEPSE unaware. 

PMID- 23970630
TI  - Sexual behaviour and sexually transmitted infections in sexually transmitted
      infection clinic attendees in the Netherlands, 2007-2011.
AB  - High annual figures of sexually transmitted infections (STIs) are diagnosed in
      the Netherlands despite significant efforts to control them. Herein, we analyse
      trends and determinants of STI diagnoses, co-infections, and sexual risks among
      visitors of 26 STI clinics between 2007 and 2011. We recorded increased
      positivity rates of STIs (chlamydia, syphilis, gonorrhoea, and/or HIV) in women
      and heterosexual men up to 12.6% and 13.4%, respectively, in 2011, while rates in
      men having sex with men (MSM) were stable but high (18.8%) through the documented
      years. Younger age, origin from Surinam/Antilles, history of previous STI,
      multiple partners, or a previous notification are the identified risk factors for
      an STI in this population. Known HIV-infected men (MSM and heterosexuals) were at
      highest risk for co-infections (relative rate heterosexual men: 15.6; MSM: 11.6).
      STI positivity rates remained high (MSM) or increased over time (women and
      heterosexual men), a fact that highlights the importance of continuing STI
      prevention. Most importantly, the very high STI co-infection rates among HIV
      positive men requires intensified STI reduction strategies to put an end to the
      vicious circle of re-infection and spread of HIV and other STIs. 

PMID- 23970631
TI  - Use of the INNO-LIA syphilis score assay in the resolution of discordant positive
      screening enzyme immunoassay results for the serological diagnosis of syphilis.
AB  - We studied the use of the INNO-LIA syphilis score assay in the resolution of
      discordant positive screening results of the Murex ICE Syphilis enzyme
      immunoassay (EIA) with the confirmatory results of both the Serodia Treponema
      pallidum particle agglutination (TPPA) and the fluorescent treponemal antibody
      absorption (FTA-Abs) assays, for the serological diagnosis of syphilis. This was
      an observational study on the serum samples received by the Syphilis Laboratory,
      Hong Kong, during the period from January 2006 to December 2012. A total of 801
      serum samples with discordant positive screening EIA results were used. Consensus
      results of such serum samples were derived from results of the EIA, TPPA and FTA
      abs assays. The age range of the individuals was 14 to 104 years (median of 52).
      There were 369 males and 432 females. Of 378 serum samples, 139 showed agreement
      among positive results, 23 of 310 showed agreement among indeterminate results
      and 277 of 465 showed agreement among negative results. The proportions of
      agreement among positive, indeterminate and negative results were 0.37 (95% CI
      0.32-0.42), 0.07 (95% CI 0.05-0.11) and 0.60 (95% CI 0.55-0.64), respectively;
      kappa 0.55 (95% CI 0.49-0.60). There were 60 serum samples with positive
      consensus results but negative INNO-LIA syphilis score results and 10 with
      negative consensus results but positive INNO-LIA syphilis score results. Although
      the INNO-LIA syphilis score assay can be considered a valid alternative
      confirmatory test for the serological diagnosis of syphilis, the present study
      showed that its use in the resolution of discordant positive screening EIA
      results was moderate. A more extensive characterization of serum samples with
      discordant reactive screening treponemal test results is necessary. 

PMID- 23970632
TI  - Prevalence of and risk factors for osteoporosis and fracture among a male HIV
      infected population in the UK.
AB  - Rates of osteoporosis and fracture may be increased in HIV but there are few UK
      data. Our aim was to examine the prevalence of and risk factors for osteoporosis
      and fractures among a homogeneous cohort of well-characterized HIV-infected men.
      In total, 168 men were recruited, median age 45 years, 37 combination
      antiretroviral therapy (cART) naive, 46 with <3 years cART exposure and 85 cART
      exposed longer term (median >10 years). All participants provided information on
      bone health and underwent DEXA scanning. Osteopenia was found in 58% of subjects
      and osteoporosis in 12%; 14% reported fractures since HIV diagnosis. Number of
      fractures since HIV diagnosis was significantly increased among those with
      osteoporosis (OR 3.5, 95% CI 1.2-10.4, p = 0.018). Duration of infection greater
      than 13 years was significantly associated with osteoporosis. Duration of cART
      was associated in univariate but not multivariate analyses. Strategies to prevent
      osteoporosis and fractures in HIV will require attention to viral and lifestyle
      factors and not just cART. 

PMID- 23970633
TI  - Factors before enrolment are associated with being removed from a Pharmacy-only
      Refill Programme at a large urban HIV/AIDS clinic, Uganda.
AB  - A Pharmacy-only Refill Programme (PRP) a type of task shifting in which stable
      HIV-positive patients are managed through pharmacy-only visits instead of
      physician visits. We performed a study to identify factors for being removed from
      the PRP in order to establish better referral criteria. The study was performed
      at the Infectious Disease Clinic (IDC) in Kampala, Uganda. We selected a random
      sample of 588 patients from 2431 patients on antiretroviral therapy referred to
      the PRP at least 12 months before commencement of the PRP evaluation. We compared
      the characteristics of patients who during 12 months of follow-up were removed
      from the PRP with those who continued to be followed up. Data were abstracted
      from the IDC data base, the pharmacy register and the patient clinical notes. Of
      588 patients, 106 (18%) were removed from the PRP. In multivariate analysis, less
      than 100% self-reported adherence to antiretroviral therapy, missing at least one
      scheduled appointment in the six months before referral to the PRP and being on a
      lopinavir/ritonavir-containing regimen were independently associated with being
      removed from the PRP. Criteria for referring patients to a PRP should focus on
      antiretroviral therapy adherence and appointment keeping. Patients on a
      lopinavir/ritonavir-containing regimen should not be targeted for a PRP. On the
      other hand a PRP is an efficient strategy that targets stable adherent patients
      in clinics with high patient load. 

PMID- 23970634
TI  - Kidney transplantation in HIV-positive adults: the UK experience.
AB  - HIV-positive patients are at increased risk of end-stage kidney disease (ESKD).
      Kidney transplantation (KT) is an established treatment modality for ESKD in the
      general population. Recent data have confirmed the feasibility of kidney
      transplantation in HIV-positive patients, and kidney transplantation is
      increasingly offered to ESKD patients with well-controlled HIV infection. We
      report clinical outcomes in a national cohort study of kidney transplantation in
      HIV-positive patients. In all, 35 HIV-positive KT recipients who had undergone KT
      up to December 2010 (66% male, 74% black ethnicity) were identified; the median
      CD4 cell count was 366, all had undetectable HIV RNA levels at kidney
      transplantation, and 44% received a kidney from a live donor. Patient survival at
      1 and 3 years was 91.3%, and graft survival 91.3% and 84.7%, respectively. At one
      year post-kidney transplantation, the cumulative incidence of acute rejection was
      48%, and the median (IQR) eGFR was 64 (46, 78) mL/min/1.73 m(2). Although HIV
      viraemia and HIV disease progression were uncommon, renal complications were
      relatively frequent. Our study corroborates the feasibility of kidney
      transplantation in HIV-positive patients. The high rates of acute rejection
      suggest that the optimal immune suppression strategy in this population remains
      to be refined. 

PMID- 23970635
TI  - Factors associated with travel to non-local genitourinary medicine clinics for
      gonorrhoea: an analysis of patients diagnosed in London, 2009-10.
AB  - We analysed factors associated with travelling to non-local genitourinary
      medicine clinics for gonorrhoea care in London. We used surveillance data on
      London residents attending genitourinary medicine clinics in 2009-10 and
      calculated distances between patients' areas of residence and both the nearest
      genitourinary medicine clinic and the clinic attended. Non-local clinics were
      attended by 5408 (46.7%) patients. Men having sex with men attended non-local
      services more than heterosexuals (OR 3.83, p < 0.001). Among heterosexual men,
      black Africans and black Caribbeans were more likely, and South Asians less
      likely, to attend non-local services compared to whites (OR [95%CI] 1.33 [1.04
      1.72], 1.36 [1.11-1.67] and 0.46 [0.31-0.70] respectively). Similar associations,
      although not statistically significant, were found in women. People were more
      likely to attend local services if their local clinic provided walk-in and young
      people's services, weekend consultations and long opening hours. These findings
      could help design services meeting local population needs and facilitate prompt
      and equitable access to care.

PMID- 23970637
TI  - Vesicular syphilid in a seropositive patient.
AB  - Syphilis is a sexually transmitted infection with various stages of evolution and
      a myriad of presentations. To avoid a delay in diagnosis, it is important to
      recognize secondary syphilis presenting with vesicular lesions. A patient
      presented with maculopapular rash of recent onset with several vesicles and
      related the eruption to paracetamol taken one day before. The differential
      diagnoses considered were drug eruption, pityriasis lichenoides et varioliformis
      acuta, pityriasis rosea and secondary syphilis. HIV, VDRL (1:256) and TPHA tests
      were positive and histopathology revealed lymphohistiocytic infiltrate and plasma
      cells. Thus, a diagnosis of secondary syphilis coexisting with HIV was confirmed.
      The patient was administered benzathine penicillin and anti-retroviral therapy
      was started. He responded very well to treatment. We report this case because of
      the rarity of vesicular eruption in secondary syphilis. 

PMID- 23970636
TI  - Depression and sexual risk behaviour among clients about to start HIV
      antiretroviral therapy in Uganda.
AB  - We investigated depression in relationship to sexual risk behaviour with primary
      partners among HIV-positive clients in Uganda. Baseline data were analyzed from a
      cohort of clients starting antiretroviral therapy. The Patient Health
      Questionnaire (PHQ-9) was used to classify depressive severity (none, minor and
      major depression) and symptom type (cognitive and somatic). Condom use was
      assessed over the past six months and during the last episode of sexual
      intercourse. A total of 386 participants had a primary sex partner, with whom
      41.6% always used condoms during sex over the past six months, and 62.4% during
      last sex. Use of a condom during last sex was associated with having no
      depression and lower PHQ-9 total and cognitive and somatic subscale scores in
      bivariate analyses; most of these relationships were marginally significant for
      intercourse over the past six months. Controlling for demographics, HIV
      disclosure and partner HIV status, only minor depression was associated with
      unprotected sex. Depressive symptoms, even if not a clinical disorder, warrant
      early detection and treatment for promoting HIV prevention among HIV-affected
      couples. 

PMID- 23970639
TI  - The two-edged sword: vasculitis associated with HIV and hepatitis C coinfection.
AB  - Vasculitis has long been associated with chronic viral infections, thus the twin
      perils of the infection and the immune response against it that bedevils the
      specialties of infection and immunity. After HIV was identified, it too became
      associated with vasculitic syndromes. Later, hepatitis C virus was also isolated,
      identified and described with its own spectrum of vasculitic diseases, including
      hepatitis C virus-associated cryoglobulinaemia. With the increasing prevalence of
      HIV and hepatitis C virus coinfection, there has come an increasing recognition
      of the range of vasculitides that can occur in this population leading to
      significant morbidity, diagnostic and treatment challenges. In this review, we
      examine the epidemiology, pathogenesis and general principles of treatment of
      these systemic diseases in HIV/hepatitis C virus coinfected individuals. 

PMID- 23970638
TI  - Using urinary leucocyte esterase tests as an indicator of infection with
      gonorrhoea or chlamydia in asymptomatic males in a primary health care setting.
AB  - To evaluate a leucocyte esterase test as a predictor of gonorrhoea or chlamydia
      in asymptomatic Aboriginal males at the Central Australian Aboriginal Congress
      Male Clinic (Ingkintja), first-void urine samples and clinical information were
      collected from consecutive asymptomatic males presenting to the Ingkintja in
      Alice Springs between March 2008 and December 2009. Urine was tested immediately
      with a leucocyte esterase test dipstick and then by polymerase chain reaction for
      gonorrhoea and chlamydia. Among the 292 specimens from asymptomatic males, 15.4%
      were positive for gonorrhoea or chlamydia. In this group, compared with
      polymerase chain reaction result for gonorrhoea or chlamydia, leucocyte esterase
      test alone and in combination with age <=35 years showed sensitivities of 66.7%
      and 60%, specificities of 90.7% and 94.7%, positive predictive values of 56.6%
      and 67.5%, negative predictive values of 93.7% and 92.8% and the area under
      receiver operating characteristics curve values of 0.79 and 0.85, respectively.
      Leucocyte esterase tests can reasonably be used as a basis for immediate
      empirical treatment for gonorrhoea or chlamydia in asymptomatic central
      Australian Aboriginal men under 35 years of age. 

PMID- 23970640
TI  - Mycobacterium avium-complex pericarditis: a case of unmasking immune
      reconstitution inflammatory syndrome.
AB  - Immune reconstitution inflammatory syndrome is a clinical entity with a broad
      presentation, described in both HIV and non-HIV-infected patients. We report a
      case of Mycobacterium avium-complex pericarditis as a rare but life-threatening
      manifestation of this syndrome in a patient with AIDS. 

PMID- 23970641
TI  - Challenges in implementing the new BASHH guidelines for the management of
      gonorrhoea.
AB  - Neisseria gonorrhoeae has progressively developed reduced sensitivity to
      different classes of antibiotics. The British Association for Sexual Health and
      HIV (BASHH) updated guidelines for the diagnosis and management of gonorrhoea in
      2011. New recommendations include an increased dose of ceftriaxone with adjuvant
      use of azithromycin, as well as test of cure (TOC) in all cases. We present an
      audit of adherence to new antibiotic prescribing guidelines as well as TOC uptake
      in an inner city genitourinary medicine clinic. Among the 271 (242 male, 29
      female) patients included, 96% (n = 260) received the new first-line treatment.
      Test of cure uptake was found to be suboptimal at 55% (n = 149) with the majority
      (67%) of these taking place within 20 days of treatment. The new first-line
      treatment for gonorrhoea is feasible and generally accepted by patients. However
      the TOC uptake is low, emphasising the need for robust follow-up and recall
      policies. Further study is required into the optimal timing for TOC. 

PMID- 23970642
TI  - Drug and sexual HIV risk behaviours related to knowledge of HIV serostatus among
      injection drug users in Houston, Texas.
AB  - This study examines the association between drug and sexual HIV risk behaviours
      and knowledge of HIV serostatus among a sample of injection drug users, recruited
      into the 2009 National HIV Behavioral Surveillance project. We calculated
      prevalence ratios and associated 95% confidence intervals of reporting a given
      risk behaviour comparing injection drug users unaware of their serostatus and HIV
      negative to HIV-positive injection drug users. Of 523 participants, 21% were
      unaware of their HIV serostatus. The three groups were not different from each
      other in terms of drug-use behaviours; however, injection drug users unaware of
      their HIV serostatus were 33% more likely to report having more than three sexual
      partners in the past 12 months and 45% more likely to report having unprotected
      sex compared to HIV-positive injection drug users. We observed markedly higher
      prevalence of sexual risk behaviours among injection drug users unaware of their
      serostatus, but drug-use risk behaviours were similar across the groups. 

PMID- 23970643
TI  - Mycobacterium kansasii septicaemia in an AIDS patient complicated by acute
      respiratory distress syndrome and acute liver failure.
AB  - Acute respiratory distress syndrome (ARDS) is a serious complication of sepsis.
      Only a few cases of non-tuberculous mycobacteria complicated by ARDS have been
      discussed in the literature to date. Mycobacterium kansasii is the most
      pathogenic non-tuberculous mycobacterium affecting the lung. In the late stages
      of acquired immunodeficiency syndrome (AIDS), it may also present as disseminated
      disease. The clinical course is usually chronic, and the time to clinical
      diagnosis can sometimes be long, requiring a careful and meticulous search for
      the pathogen. To our knowledge, this is the first case report of disseminated M.
      kansasii infection complicated by ARDS and acute liver failure in a patient with
      end-stage AIDS. 

PMID- 23970644
TI  - The prevalence of human immunodeficiency virus and sexually transmitted
      infections among female sex workers in Shiraz, South of Iran: by respondent
      driven sampling.
AB  - As a concentrated epidemic, human immunodeficiency virus (HIV) is spreading
      rapidly in one or more groups in Iran, but in the general population its
      prevalence is relatively low. Female sex workers (FSWs) and their partners are at
      greater risk for HIV infection. To determine the prevalence of HIV and sexually
      transmitted infections (STIs) including gonorrhoea, Chlamydia, herpes simplex
      type 2 and syphilis among FSWs. We conducted a cross-sectional study of 278 FSWs
      in Shiraz, by using respondent-driven sampling, from June to March 2010. The
      recruitment chain started with 14 seeds, and FSWs were tested for HIV, syphilis,
      herpes simplex type 2, gonorrhoea and Chlamydia. HIV prevalence was 4.7%
      (13/278); the most prevalent STI was herpes simplex type 2, 9.7% (27/278),
      followed by Chlamydia 9% (25/278), gonorrhoea 1.4% (4/278) and syphilis (0/278).
      The FSWs reported drug use (69.9%) of which 16.4% had history of injecting drug
      use. Unprotected sex in the past month was reported by 24.4% of FSWs. Urgent
      education and risk reduction programmes are needed in this population. 

PMID- 23970645
TI  - Polyactin A increases CD4(+) T-cell counts in HIV-infected individuals with
      insufficient immunologic response to highly active antiretroviral therapy.
AB  - We conducted a study to determine whether an immunomodulator, polyactin A, is
      able to enhance the immunologic response in patients with insufficient
      immunologic response to highly active antiretroviral therapy. From 783 patients,
      48 were eligible and were randomly assigned to an experimental group receiving
      polyactin A for 3 months or a control group. CD4(+) T-cell counts in the
      experimental group increased from 201 +/- 31 to 228 +/- 38 cells/ul after
      treatment (p < 0.001). CD4(+) T-cell counts in the control group and CD8(+) T
      cell counts and CD4(+)/CD8(+) ratios in both groups did not differ significantly
      between baseline and month 3. The experimental group had a higher CD4(+) T-cell
      count than the control group at month 3 (228 +/- 38 versus 205 +/- 35, p < 0.05).
      Our work demonstrated that polyactin A can increase CD4(+) T-cell counts in
      patients with insufficient immunologic response to highly active antiretroviral
      therapy, but further studies are required to determine its clinical benefits. 

PMID- 23970646
TI  - Contraceptive choice and acceptability: the future for STI risk in Kelantan,
      Malaysia.
AB  - More than 150 million women become pregnant in developing countries annually and
      an estimated 287,000 die from pregnancy-related causes. Contraception is vital to
      prevent unnecessary maternal deaths, as well as sexually transmitted infections.
      The objective of this study was to investigate preferred contraceptive methods
      and the factors that influence contraceptive choice among women in Kelantan,
      Malaysia. A cross-sectional study using interview-based questionnaires was
      conducted, during July and August 2009, in local family planning clinics in
      Kelantan. The questionnaire was administered to adult women (age 20-50).
      Prevalence of unplanned pregnancies was high (48%). Contraceptive preference was
      Depo contraceptive injection (32%), oral contraceptive pills (27%), intrauterine
      devices (15%) and contraceptive implants (12%); 9% used condoms. Only 2% used
      contraception to protect against sexually transmitted infections or HIV/AIDS.
      Younger women (OR 0.90; 95% CI 0.807-0.993) were more likely to use
      contraception. In conclusion, non-interrupted contraceptive methods were
      preferred. More than 60% would stop using contraception if it interrupted
      intercourse. From both a public health and infectious disease perspective, this
      is extremely worrying.

PMID- 23970647
TI  - Recurrent giant molluscum contagiosum immune reconstitution inflammatory syndrome
      (IRIS) after initiation of antiretroviral therapy in an HIV-infected man.
AB  - We describe an HIV-infected South African man who experienced two distinct
      episodes of disseminated giant molluscum contagiosum immune reconstitution
      inflammatory syndrome (IRIS) over a six-year period. The first episode of
      molluscum contagiosum IRIS occurred with rapid virologic suppression following
      antiretroviral therapy initiation. The second episode occurred during a rapid
      increase in CD4 cells following stable viral suppression with second-line
      antiretroviral therapy. His molluscum contagiosum lesions then completely
      resolved during a reduction in CD4 count, despite maintaining virologic
      suppression. Nearly one year after the resolution of his giant molluscum
      contagiosum IRIS lesions, he maintains an undetectable viral load, but his level
      of immune deficiency has not improved. In the absence of well-controlled
      therapeutic trials, molluscum contagiosum IRIS presents important management
      challenges.

PMID- 23970648
TI  - Rash and hepatitis within days of starting a new antiretroviral regimen:
      nevirapine hypersensitivity, secondary syphilis or both?
AB  - We report a case in which an HIV-positive man developed general malaise, skin
      rash and biochemical hepatitis within days of starting a nevirapine-based
      antiretroviral treatment regimen. At the same time, his syphilis serology proved
      positive. We discuss the diagnostic dilemma: was this a nevirapine
      hypersensitivity reaction, secondary syphilis or both?

PMID- 23970649
TI  - Frequency and risk factors for distal sensory polyneuropathy in HIV infection in
      a developing country.
AB  - Distal sensory polyneuropathy is a source of morbidity in HIV infection. This
      study aims to determine the frequency and effect of demographic and clinical
      variables on distal sensory polyneuropathy, among HIV-positive participants in
      south-east Nigeria. The study involved highly active antiretroviral therapy
      (HAART)-naive, patients on HAART and HIV-negative matched controls conducted at
      the University of Nigeria Teaching Hospital, Enugu south-east Nigeria. Distal
      sensory polyneuropathy was diagnosed with clinical evaluation and the use of Bio
      Thesiometer, 10 g monofilament and ankle reflex. There were 100 participants in
      each of the groups, comprising 109 (36.3%) men and 191 (63.7%) women, with median
      age of 35 years. About 42.5% (85/200) of the HIV-positive participants (37 drug
      naive and 48 on HAART) had distal sensory polyneuropathy. None in the control
      group had distal sensory polyneuropathy. Age (p = 0.02), height (p = 0.002), low
      haemoglobin (p = 0.03) and mean duration on HAART (p = 0.006) were significantly
      associated with distal sensory polyneuropathy, while gender (p = 0.497), body
      mass index (p = 0.657) and CD4 count (p = 0.482) did not affect distal sensory
      polyneuropathy. Low haemoglobin, height, and duration on HAART were independent
      risk factors for distal sensory polyneuropathy. Addressing correctable causes of
      anaemia, and alternatives to neurotoxic HAART may minimize the risk of distal
      sensory polyneuropathy.

PMID- 23970650
TI  - Disseminated tuberculosis after extracorporeal shock-wave lithotripsy in an AIDS
      patient presenting with urosepsis.
AB  - Haematogenous dissemination of undiagnosed urinary tuberculosis after performing
      extracorporeal shock-wave lithotripsy (ESWL) is extremely rare. Herein, we report
      a 41-year-old male who presented with urosepsis to the emergency room;
      catheterization was performed and retention resolved. He had a tattoo on his left
      arm and a five-year history of intravenous drug use. Blood tests indicated
      anaemia, leukocytosis, elevated CRP and ESR and mild hyponatraemia; haematuria,
      moderate bacteriuria and 2+ proteinuria on urinanalysis were observed. Chest X
      ray revealed lesions suggestive of miliary tuberculosis, which was confirmed by
      chest CT scan. Brain CT and MRI suggested brain involvement in the setting of
      tuberculosis. On further investigations, HIV infection and hepatitis C
      seropositivity were detected and the patient remained in a coma for five days
      with a Glasgow Coma Scale of 6/15. Finally, the diagnosis of haematogenous
      dissemination of tuberculosis following lithotripsy was established. Anti
      tuberculosis and anti-retroviral therapy were prescribed and monthly follow-up
      visits were scheduled. In conclusion, in a patient diagnosed with
      ureterolithiasis, a thorough history and physical examination, with specific
      attention to HIV and tuberculosis predisposing factors, should be carried out and
      preoperative screening tests considering the possibility of urinary tuberculosis
      are required. Finally, if urinary tuberculosis is detected, ESWL must be
      postponed until after appropriate treatment of tuberculosis.

PMID- 23970651
TI  - Sleep quality in efavirenz-treated Chinese HIV patients - comparing between GT
      and GG genotype of CYP2B6-516 G/T polymorphisms.
AB  - Seventy-two adult Chinese HIV-positive treatment-naive patients were recruited in
      a study to evaluate prospectively the associations between CYP2B6 516 G/T
      polymorphisms and sleep quality following treatment with an efavirenz-based
      regimen. Overall, the patients gave an allelic frequency of 0.3 for CYP2B6 516 T,
      and a genotype frequency of 9.4% for TT. Compared to GG, GT gave a higher median
      value of plasma efavirenz level at four weeks (3.77 mg/L vs 2.59 mg/L, p < 0.001)
      and 12 months (3.57 mg/L vs 2.97 mg/L, p = 0.026). Using generalised estimating
      equations analysis to track the variance over time, there was poorer Pittsburgh
      Sleep Quality Index in GT compared to GG, while GT was associated with a higher
      efavirenz level of >4 mg/L. There was however no difference in the component
      sleep scores nor was there direct association between sleep quality and plasma
      efavirenz levels. The results suggested that CYP2B6 genotype was associated with
      different patterns of sleep problems, further investigation of which is warranted
      with the objective of optimizing therapy with efavirenz-based regimens.

PMID- 23970652
TI  - A cross-sectional evaluation of the prevalence and associations of HIV among
      female sex workers in the Gambia.
AB  - To determine HIV prevalence among female sex workers in the Gambia and HIV risk
      factors, we accrued participants (n = 251) through peer-referral and venue-based
      recruitment. Blood samples were screened for HIV and participants were
      administered a questionnaire. Bivariate and multivariate logistic regression
      identified factors associated with HIV status. Forty respondents (15.9%) were HIV
      positive: 20 (8.0%) were infected with HIV-1 only, 10 (4.0%) with HIV-2 only, and
      10 (4.0%) with both HIV-1 and HIV-2; 12.5% (n = 5/40) knew their status. Condom
      usage at last sex was 97.1% (n = 170/175) with new clients and 44.2% (n = 53/120)
      with non-paying partners. Having a non-paying partner, living with relatives or
      friends, having felt scared to walk in public, selling sex in multiple locations,
      and recent depressive symptoms were positively associated with HIV under
      multivariate regression. Female sex workers have a higher prevalence of HIV
      compared to the general Gambian population. Interventions should be rights-based,
      promote safer sex practices and regular testing for female sex workers and
      linkage to HIV treatment and care with adherence support for those living with
      HIV. In addition, service providers should consider non-paying partners of female
      sex workers, improve knowledge and availability of condoms and lubricant, and
      address safety and mental health needs.

PMID- 23970653
TI  - The impact of comprehensive prevention of mother-to-child HIV transmission in
      Dehong prefecture, Yunnan province, 2005-2010: a hard-hit area by HIV in Southern
      China.
AB  - The burden of HIV/AIDS in China has been disproportionately concentrated in
      Yunnan Province, where in Dehong prefecture, the HIV prevalence rate among
      pregnant women reached 1.3% in 2003, a rate that is indicative of a generalized
      epidemic. Since then, there have been extensive efforts to expand prevention to
      reduce mother-to-child transmission (MTCT) in this high-prevalence region. These
      intensified MTCT reduction efforts and their impact on MTCT are yet to be
      examined. We described the changes in access to HIV screening and antiretroviral
      therapy (ART) among pregnant women from 2005 to 2010 in this region and the
      corresponding reduction in MTCT over this period. Between 2005 and 2010, the
      annual number of pregnant women screened for HIV in Dehong Prefecture more than
      doubled. The proportion of pregnant women screened for HIV rose from an estimated
      15-20% to 99.8%, and the proportion of HIV-infected pregnant women receiving ART
      increased from 63% to 99%. We estimate that the proportion of children born with
      HIV to HIV-infected mothers decreased from 15.4% to 7.2% over this period.
      Sustained low-level MTCT following comprehensive interventions in this region is
      encouraging. Over the last decade, comprehensive PMTCT efforts, coupled with
      national and local government policy support in this area appear to be effective.

PMID- 23970654
TI  - Lung cancer in HIV-infected patients.
AB  - Our objective was to determine the prevalence and characteristics of lung cancer
      (LC) in HIV patients and compare them with LC patients from the general
      population. All HIV patients diagnosed at three hospitals in Malaga (southern
      Spain) who developed LC during January 1989-June 2012 were reviewed. They were
      compared with a sample of patients with LC taken from the Pneumology and Oncology
      Department of the Hospital Virgen de le Victoria (Malaga) during the same period.
      Of the 4721 HIV patients (83% men) followed-up during the study period, 61
      (1.29%) developed LC: 82% were men, mean age 48 years, all except two were
      smokers, 47.5% had a prior lung infection, and the median CD4 count was 237
      cells/mm(3). Forty (65.5%) patients were on antiretroviral therapy at LC
      diagnosis (70% had an undetectable viral load). The HIV-negative group was older
      at diagnosis, contained fewer active smokers, had a greater frequency of the
      squamous cell carcinoma histological subtype and fewer cases of adenocarcinoma.
      Presentation was advanced in both groups and the median survival of HIV patients
      was three months. LC is a common tumour in HIV patients. It affects men and women
      equally, with a history of smoking and often a prior opportunistic lung disease.
      Affected patients are often immunosuppressed and have had an AIDS-related
      diagnosis. 

PMID- 23970655
TI  - Performance evaluation of a new fourth-generation HIV Ag/Ab combination
      electrochemiluminescence immunoassay - evaluation of a new HIV assay.
AB  - A new fourth-generation HIV Ag/Ab electrochemiluminescence immunoassay for
      screening of HIV infection, the Elecsys HIV Combi PT (Roche Diagnostics,
      Penzberg, Germany) assay, is going to be commercially available in clinical
      laboratories in China. This assay was evaluated and compared with two commonly
      used assays: Elecsys HIV Combi assay and the Livzon anti-HIV-1/2 ELISA.
      Commercially available panels and 30 established HIV infection samples were
      tested to evaluate the sensitivity. In addition, a total of 675 routine clinical
      samples were collected and tested in West China Hospital to compare the
      specificity. Any reactive result from a screening test was retested and all
      reactive retested samples were confirmed with Western blot assay, Elecsys HIV Ag
      test, Elecsys HIV Ag confirmatory test or HIV-1 RNA NAT testing. According to the
      results of the HIV seroconversion panels, the Elecsys HIV Combi PT could detect
      seroconversion at the same bleed or at least one bleed earlier compared to the
      other two assays. Among the 675 clinical samples, most results were consistent
      except for one specimen with a false-negative result using Elecsys HIV Combi
      assay. In conclusion, the Elecsys HIV Combi PT has shown satisfactory sensitivity
      and specificity to be a screening test for HIV infection.

PMID- 23970656
TI  - 2012 BASHH statement on partner notification for sexually transmissible
      infections.

PMID- 23970657
TI  - Changing trends in HIV diagnosis in an inner city London teaching hospital 2007
      2011.
AB  - In 2008, guidelines aimed at reducing undiagnosed HIV infection were published,
      recommending normalization of testing. Local initiatives were carried out in
      south-west London including an extensive primary care education programme. This
      study aimed to establish the impact of these initiatives on HIV diagnoses. Data
      on all new diagnoses referred to our centre were collected and analysed from
      patient records. A total of 394 patients were newly diagnosed with HIV from 2007
      to 2011. Diagnosis in primary care and other non-sexual health (SH) settings
      increased by 184% during this period. There was an increase of 37% in the median
      CD4 count at diagnosis, taking the figure to 372 cells/mm3 in 2011. The
      proportion of patients presenting with a CD4 count of <200cells/mm3 decreased by
      24%. The evidence suggests that these local initiatives were successful in
      increasing HIV diagnoses outside SH settings, particularly in very late
      presenters.

PMID- 23970658
TI  - Prevalence, clinical features and quantification of genital non-viral infections.
AB  - We conducted a study of the prevalence, clinical features and microscopy
      findings, by retrospective case-notes survey, of six non-viral organisms, among
      1718 attendees at a genitourinary (GU) medicine clinic in England. An in-house
      assay for six non-viral infections was used and quantitation of ureaplasmas
      performed. The prevalences of the six organisms were: Chlamydia trachomatis (CT),
      7.1%; Neisseria gonorrhoeae (NG), 0.6%; Mycoplasma genitalium (MG), 1.0%;
      Trichomonas vaginalis, 0.2%; Ureaplasma urealyticum, 16.1%; Ureaplasma parvum,
      35.6%. Among men (but not women) there were significantly raised odds ratios
      compared with that for U. parvum, for the symptom of discharge with CT, 7.30; MG,
      6.43; NG 19.29; dysuria with CT, 5.89 and MG, 5.95; and the microscopy finding of
      >4 pus cells per high power field with: CT, 7.22; MG, 4.58 and NG 22.31.
      Evaluation of a possible link between quantitation of U. urealyticum and
      urethritis did not confirm research findings elsewhere. 

PMID- 23970659
TI  - Audio computer-assisted survey instrument versus face-to-face interviews: optimal
      method for detecting high-risk behaviour in pregnant women and their sexual
      partners in the south of Brazil.
AB  - Audio computer-assisted survey instrument (ACASI) has been shown to decrease
      under-reporting of socially undesirable behaviours, but has not been evaluated in
      pregnant women at risk of HIV acquisition in Brazil. We assigned HIV-negative
      pregnant women receiving routine antenatal care at in Porto Alegre, Brazil and
      their partners to receive a survey regarding high-risk sexual behaviours and drug
      use via ACASI (n = 372) or face-to-face (FTF) (n = 283) interviews. Logistic
      regression showed that compared with FTF, pregnant women interviewed via ACASI
      were significantly more likely to self-report themselves as single (14% versus
      6%), having >5 sexual partners (35% versus 29%), having oral sex (42% versus
      35%), using intravenous drugs (5% versus 0), smoking cigarettes (23% versus 16%),
      drinking alcohol (13% versus 8%) and using condoms during pregnancy (32% versus
      17%). Therefore, ACASI may be a useful method in assessing risk behaviours in
      pregnant women, especially in relation to drug and alcohol use. 

PMID- 23970661
TI  - Associated factors for HIV and syphilis infection among men who have sex with men
      only and men who have sex with both men and women in cities of China.
AB  - The aims of this paper were to find out the status of HIV and syphilis infection
      and to examine the sexual behaviours between men who have sex with men only
      (MSM/M) and men who have sex with both men and women (MSM/W), as well as to
      determine the correlates for HIV and syphilis infection among MSM/M and MSM/W,
      respectively. Among 1693 MSM who participated in the study, the proportions of
      MSM/M and MSM/W were 82.1% and 17.9%, respectively. The prevalences of HIV
      infection were 7.0% in MSM/M and 6.6% in MSM/W and the prevalences of syphilis
      infection were 11.9% and 13.2%, respectively. Among the MSM/M subset, the
      correlates both for HIV and syphilis infection included having more sexual
      partners, and being receptive or both insertive and receptive for anal sex. Among
      the MSM/W subset, living in Chengdu was associated with HIV infection and using
      condoms inconsistently during anal sex was associated with syphilis infection.
      The findings of this survey call for interventions tailored according to the
      needs of different subsets of MSM. 

PMID- 23970660
TI  - History of intimate partner violence is associated with sex work but not sexually
      transmitted infection among HIV-positive female drinkers in Russia.
AB  - This paper assesses the associations between intimate partner violence (IPV) and
      sexually transmitted infections (STIs) and sexual risks among HIV-positive female
      drinkers in St Petersburg, Russia. Survey and STI data were analysed from 285
      women in HERMITAGE, a secondary prevention study of HIV-positive heavy drinkers.
      Logistic and Poisson regression analyses assessed associations of IPV with STI
      and risky sex. Most women (78%) experienced IPV and 19% were STI positive; 15%
      sold sex. IPV was not significantly associated with STI, but was with selling sex
      (adjusted odds ratio = 3.56, 95% confidence interval = 1.02-12.43). In
      conclusion, IPV is common and associated with sex trade involvement among Russian
      HIV-positive female drinkers. 

PMID- 23970662
TI  - Is out-of-pocket cost a barrier to receiving repeat tests for chlamydia and
      gonorrhoea?
AB  - We aimed to examine whether out-of-pocket (OOP) costs associated with chlamydia
      (CT) and gonorrhoea (GC) screening tests is a barrier to receiving CT/GC re
      screening and follow-up annual screening. A major health insurance claims
      database 2006-2010 was used for analysis. The date of first CT/GC diagnosis was
      used as the index date, and OOP costs at index date for screening tests were
      retrieved. A re-screening test and an annual screening were defined as tests that
      occurred within 90-180 days and 181-395 days of the index date, respectively. Re
      screening rates were 11.7% and 10.9% and annual screening rates were 24.7% and
      23.7% for CT and GC cases, respectively. Compared with the CT patients without
      OOP expenses, those with OOP expenses of $30 or higher had significantly reduced
      likelihood of receiving re-screening and annual screening. Similar results were
      found for GC patients. We concluded that OOP costs serve as a significant barrier
      to re-screening and annual screening. 

PMID- 23970663
TI  - Opt-out testing for HIV: perspectives from a high prevalence community in south
      east England, UK.
AB  - Peoples' perspectives and attitudes towards being offered opt-out HIV testing
      were explored in a geographical area of high HIV prevalence. Users (n = 31) of
      sexually transmitted infection (STI) testing services took part in community
      focus groups in the south-east of England, UK. There was broad support for opt
      out HIV testing based on public health and individual health benefits. For this
      sample, opt-out HIV testing when registering with a general practice surgery and
      on elective or emergency admission to a general hospital was acceptable, although
      there were concerns about the rigour of informed consent. Heterosexual
      participants' criticism of people from higher prevalence groups for HIV declining
      tests, while maintaining their own right to opt-out, suggested that attitudes
      towards testing may be influenced by levels of perceived risk. Innovations in HIV
      testing policies to increase testing rates will benefit from an acknowledgement
      of the different meanings that testing has. 

PMID- 23970664
TI  - HIV, hepatitis B/C and syphilis prevalence and risk behaviors among gay,
      transsexuals and men who have sex with men, Dominican Republic.
AB  - This study investigated HIV, hepatitis B (HBV) and C (HCV) and syphilis
      prevalence and associated behavioural correlates to HIV infection among gay,
      transsexuals and men who have sex with men (GTMSM) in the Dominican Republic
      using respondent-driven sampling. Eligible men were aged >=15 years, reported
      engaging in anal/oral sex with another man within the past six months and living
      in one of the four cities sampled. GTMSM were recruited in Santo Domingo (n =
      510), Barahona (n = 281), La Altagracia (n = 270) and Santiago (n = 327). HIV
      seroprevalence ranged from 5.1% to 7.6%. HBV ranged from 0.6% to 3.5%, HCV from
      0.8% to 6.9% and syphilis from 3.5% to 6.9%. GTM practice numerous risky sexual
      behaviours including having multiple sex partners and practising inconsistent
      condom use with male and female, including transactional, sex partners. Although
      we found lower HIV prevalence compared with previous studies, the high level of
      extremely risky sexual behaviours practised by GTM in the Dominican Republic will
      most likely result in increases in HIV and other infections if action is not
      taken to scale-up effective prevention programmes for this population. 

PMID- 23970665
TI  - Expanding sexually transmitted infection screening among women and men engaging
      in transactional sex: the feasibility of field-based self-collection.
AB  - Routine screening is a key component of sexually transmitted infection (STI)
      prevention and control; however, traditional programmes often fail to effectively
      reach men and women in hidden communities. To reduce prevalence, we must
      understand the programmatic features that would encourage utilization of services
      among asymptomatic individuals. Using incentivized snowball sampling, 44 women
      and men recently engaging in transactional sex were recruited (24 women, 20 men);
      median age 37 years. Respondents were offered the opportunity to collect genital,
      oropharyngeal and rectal samples for STI testing and completed a face-to-face
      interview about their experience with self-obtained sampling. Interviews were
      analysed using qualitative methods. Participants were unaware of potential risk
      for STI, but found self-sampling in non-clinical settings to be acceptable and
      preferable to clinic-based testing. All participants collected genital specimens;
      96% and 4% collected oropharyngeal and rectal specimens, respectively. The burden
      of disease in this population was high: 38% tested positive for at least one STI.
      We detected multiple concomitant infections. Incorporating field collection of
      self-obtained samples into STI control programmes may increase utilization among
      high-risk populations unlikely to access clinic-based services. High infection
      rates indicate that individuals engaging in transactional sex would benefit from,
      and be responsive to, community-based self-sampling for STI screening. 

PMID- 23970666
TI  - A survey of HIV care in the UK: results of British HIV association (BHIVA)
      national audit 2010.
AB  - The aim of the 2010 BHIVA audit was to assess the impact of the 2008 UK HIV
      testing guidelines on clinical practice. Here, we report one aspect of the audit
      comprising a survey of local testing policy and practice at centres providing
      adult HIV services across the UK. Selected recommendations from the 2008 national
      HIV testing guidelines were assessed as target outcomes and the percentages of
      sites and subjects meeting these recommendations were calculated. One hundred and
      thirty-two sites responded to the survey and many are actively promoting HIV
      testing locally. Sites report HIV testing is routine in genitourinary (GU)
      medicine and antenatal services but offered selectively in other clinical areas.
      Encouragingly, 21 (16%) report some local general practitioner practices are
      offering testing routinely to new patients at registration. However, the time to
      receive non-urgent HIV test results exceeds 72 hours in 29% of sites. In
      conclusion, HIV testing needs to continue to expand across clinical settings to
      reduce the number of patients living with undiagnosed infection. Laboratory
      turnaround time needs to improve to ensure non-urgent HIV test results are
      available within 72 hours. 

PMID- 23970667
TI  - Pulmonary cryptosporidiosis and immune reconstitution inflammatory syndrome: a
      case report and review.
AB  - Cryptosporidium rarely affects the lungs, and is not typically associated with
      the immune reconstitution inflammatory syndrome (IRIS). We describe the first
      published case of pulmonary IRIS following the initiation of antiretroviral
      therapy in a patient with AIDS and pulmonary cryptosporidiosis, and discuss its
      implications for HIV patient care. 

PMID- 23970668
TI  - Maintaining science eminence.

PMID- 23970672
TI  - Research funding. Diplomatic flap threatens E.U.-Israeli research ties.

PMID- 23970673
TI  - Newsmaker interview: Charles Sobeck. How NASA tried to save its prime planet
      spotter. Interview by Yudhijit Bhattacharjee.

PMID- 23970674
TI  - Scientific publishing. Half of all papers now free in some form, study claims.

PMID- 23970675
TI  - Demography. Can China age gracefully? A massive survey aims to find out.

PMID- 23970677
TI  - Planetary science. The save-the-world foundation.

PMID- 23970676
TI  - The CRISPR craze.

PMID- 23970678
TI  - Archaeobotanical archiving.

PMID- 23970679
TI  - Archaeobotanical archiving--response.

PMID- 23970680
TI  - Alleviating poverty in India: biodiversity's role.

PMID- 23970681
TI  - Protecting the right to benefit from science.

PMID- 23970682
TI  - Protecting the right to benefit from science--response.

PMID- 23970684
TI  - Education. Can rating pre-K programs predict children's learning?

PMID- 23970685
TI  - Conservation. A critical crossroad for BLM's wild horse program.

PMID- 23970686
TI  - Genetics. Mysterious ribosomopathies.

PMID- 23970687
TI  - Geophysics. Megacity megaquakes--two near misses.

PMID- 23970688
TI  - Geochemistry. An arsenic forecast for China.

PMID- 23970689
TI  - Medicine. Gene therapy that works.

PMID- 23970690
TI  - Chemistry. Nucleation from solution.

PMID- 23970691
TI  - Physiology. The health risk of obesity--better metrics imperative.

PMID- 23970692
TI  - Materials science. Functional ion defects in transition metal oxides.

PMID- 23970693
TI  - Tissue interactions in neural crest cell development and disease.
AB  - The neural crest is a transient population of migratory cells in the embryo that
      gives rise to a wide variety of different cell types, including those of the
      peripheral nervous system. Dysfunction of neural crest cells (NCCs) is associated
      with multiple diseases, such as neuroblastoma and Hirschsprung disease. Recent
      studies have identified NCC behaviors during their migration and differentiation,
      with implications for their contributions to development and disease. Here, we
      describe how interactions between cells of the neural crest and lineages such as
      the vascular system, as well as those involving environmental signals and
      microbial pathogens, are critically important in determining the roles played by
      these cells. 

PMID- 23970694
TI  - Groundwater arsenic contamination throughout China.
AB  - Arsenic-contaminated groundwater used for drinking in China is a health threat
      that was first recognized in the 1960s. However, because of the sheer size of the
      country, millions of groundwater wells remain to be tested in order to determine
      the magnitude of the problem. We developed a statistical risk model that
      classifies safe and unsafe areas with respect to geogenic arsenic contamination
      in China, using the threshold of 10 micrograms per liter, the World Health
      Organization guideline and current Chinese standard for drinking water. We
      estimate that 19.6 million people are at risk of being affected by the
      consumption of arsenic-contaminated groundwater. Although the results must be
      confirmed with additional field measurements, our risk model identifies numerous
      arsenic-affected areas and highlights the potential magnitude of this health
      threat in China. 

PMID- 23970695
TI  - Hillslopes record the growth and decay of landscapes.
AB  - Earth's surface archives the combined history of tectonics and erosion, which
      tend to roughen landscapes, and sediment transport and deposition, which smooth
      them. We analyzed hillslope morphology in the tectonically active Dragon's Back
      Pressure Ridge in California, United States, to assess whether tectonic uplift
      history can be reconstructed using measurable attributes of hillslope features
      within landscapes. Hilltop curvature and hillslope relief mirror measured rates
      of vertical displacement caused by tectonic forcing, and their relationships are
      consistent with those expected when idealizing hillslope transport as a nonlinear
      diffusion process. Hilltop curvature lags behind relief in its response to
      changing erosion rates, allowing growing landscapes to be distinguished from
      decaying landscapes. Numerical modeling demonstrates that hillslope morphology
      may be used to infer changes in tectonic rates. 

PMID- 23970696
TI  - Abundant porewater Mn(III) is a major component of the sedimentary redox system.
AB  - Soluble manganese(III) [Mn(III)] can potentially serve as both oxidant and
      reductant in one-electron-transfer reactions with other redox species. In near
      surface sediment porewater, it is often overlooked as a major component of Mn
      cycling. Applying a spectrophotometric kinetic method to hemipelagic sediments
      from the Laurentian Trough (Quebec, Canada), we found that soluble Mn(III),
      likely stabilized by organic or inorganic ligands, accounts for up to 90% of the
      total dissolved Mn pool. Vertical profiles of dissolved oxygen and dissolved and
      solid Mn suggest that soluble Mn(III) is primarily produced via oxidation of
      Mn(II) diffusing upwards from anoxic sediments with lesser contributions from
      biotic and abiotic reductive dissolution of MnO2. The conceptual model of the
      sedimentary redox cycle should therefore explicitly include dissolved Mn(III). 

PMID- 23970697
TI  - Microscopic evidence for liquid-liquid separation in supersaturated CaCO3
      solutions.
AB  - Recent experimental observations of the onset of calcium carbonate (CaCO3)
      mineralization suggest the emergence of a population of clusters that are stable
      rather than unstable as predicted by classical nucleation theory. This study uses
      molecular dynamics simulations to probe the structure, dynamics, and energetics
      of hydrated CaCO3 clusters and lattice gas simulations to explore the behavior of
      cluster populations before nucleation. Our results predict formation of a dense
      liquid phase through liquid-liquid separation within the concentration range in
      which clusters are observed. Coalescence and solidification of nanoscale droplets
      results in formation of a solid phase, the structure of which is consistent with
      amorphous CaCO3. The presence of a liquid-liquid binodal enables a diverse set of
      experimental observations to be reconciled within the context of established
      phase-separation mechanisms. 

PMID- 23970698
TI  - Conformational motions regulate phosphoryl transfer in related protein tyrosine
      phosphatases.
AB  - Many studies have implicated a role for conformational motions during the
      catalytic cycle, acting to optimize the binding pocket or facilitate product
      release, but a more intimate role in the chemical reaction has not been
      described. We address this by monitoring active-site loop motion in two protein
      tyrosine phosphatases (PTPs) using nuclear magnetic resonance spectroscopy. The
      PTPs, YopH and PTP1B, have very different catalytic rates; however, we find in
      both that the active-site loop closes to its catalytically competent position at
      rates that mirror the phosphotyrosine cleavage kinetics. This loop contains the
      catalytic acid, suggesting that loop closure occurs concomitantly with the
      protonation of the leaving group tyrosine and explains the different kinetics of
      two otherwise chemically and mechanistically indistinguishable enzymes. 

PMID- 23970699
TI  - Testing times: testing patient acceptance and ability to self-screen for a No
      Talk Testing service.
AB  - Genitourinary medicine (GUM) departments need to be resource efficient to manage
      the increasing numbers of patients seeking to access services. At the Edinburgh
      GUM department, we wished to develop a new No-Talk Testing (NTT) clinic for
      asymptomatic, low-risk patients attending for routine sexually transmitted
      infection (STI) screening. We undertook a questionnaire feasibility study to
      determine patient acceptability and ability to self-screen for this service. A
      total of 267 respondents completed questionnaires regarding acceptability of a
      future NTT service; 227 agreed to comparison of their self-screen with clinician
      risk-assessment. Overall, patient acceptability for a future NTT service was
      high, with an average of 7.8/10 awarded for opinion. Seventy-three percent of
      patients agreed they would consider utilizing such a service in the future. Sixty
      one percent of respondents suggested at least one benefit to a future NTT
      service; principally, prospects for increased speed, efficiency, capacity and
      reduced waiting times. Comparing STI risk self-assessment with clinician
      assessment, discrepancies were identified for 37% of individuals. However, a
      majority (70%) of the discrepancies identified were due to a risk being noted in
      the self-screen alone, and missed from clinician notes. In summary, the study
      demonstrated NTT as acceptable and feasible. Based on these results, we have now
      successfully introduced such a service within our department.

PMID- 23970700
TI  - Seroprevalence of HSV-1 and HSV-2 antibodies in Canadian women screened for
      enrolment in a herpes simplex virus vaccine trial.
AB  - Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) infections continue to be among
      the most common and unrecognized sexually transmitted infections in the world.
      Although treatable, HSV-1 and HSV-2 infections remain incurable. Hence, there is
      interest in the development of a vaccine to prevent genital herpes. As part of a
      multicentre, randomized, placebo-controlled trial to test such a vaccine, healthy
      women 18-30 years were enrolled as volunteers in several Canadian centres between
      2005 and 2007. This study reports the seroprevalence of HSV-1 and HSV-2
      antibodies in this group. A total of 2694 adult female volunteers in Canada with
      no known history of herpes simplex were screened for HSV antibodies using Western
      blot assay (the gold standard for diagnosis of HSV) for potential participation
      in a randomized, double-blind efficacy field trial of a herpes simplex vaccine.
      This trial provides a unique opportunity to examine the prevalence of antibodies
      to HSV-1 and of antibodies to HSV-2 in women with no known history of herpes
      simplex infection. The prevalence of antibodies to HSV-1 and to HSV-2 is compared
      with that found in previous Canadian studies that focused on a more general
      population. The overall seroprevalence of antibody to HSV-1 was 43%; that of HSV
      2 was 2.5% and seropositivity to both was 2%. The prevalence of antibody to both
      HSV-1 and to HSV-2 increased with age. Seronegativity to both HSV-1 and HSV-2 was
      56% in participating centres with populations under 250,000 and 46% in
      participating centres with populations over 250,000. Significant racial
      differences in seropositivity to HSV-1 and to HSV-2 were noted. The likelihood of
      participants being seropositive to HSV-1 and to HSV-2 was found to increase with
      age and to positively correlate with the population of the city in which they
      resided. Hypotheses are proposed to account for differences in racial
      seropositivity to HSV-1 and to HSV-2.

PMID- 23970701
TI  - Neurocognitive impairment in HIV-infected individuals with previous syphilis.
AB  - Cognitive impairment is common in HIV-infected individuals, as is syphilis.
      Treponema pallidum, the bacterium that causes syphilis, invades the central
      nervous system early in disease. We hypothesized that HIV-infected patients with
      a history of syphilis or neurosyphilis would have more cognitive impairment than
      HIV-infected individuals without these infections. Eighty-two of 1574 enrollees
      in CHARTER, a prospective, observational study, had reactive serum rapid plasma
      reagin (RPR) tests. They were matched to 84 controls with non-reactive RPR by
      age, gender, ethnicity and HIV risk factor. Participants underwent comprehensive
      neuropsychological (NP) evaluations. RPR results were confirmed and serum
      fluorescent treponemal antibody absorption (FTA-ABS) test reactivity determined
      at a central laboratory. Sera from 101 of 166 participants were FTA-ABS reactive,
      indicating past or current syphilis. Among the 136 individuals without
      confounding conditions, compared with patients who had never had syphilis, those
      with prior syphilis had a greater number of impaired NP test domains (1.90 SD
      [1.77] versus 1.25 [1.52], P = 0.03), a higher global deficit score (0.47 [0.46]
      versus 0.31 [0.33], P = 0.03), and more were impaired in the NP learning domain
      (36 [42.9%] of 84 versus 13 [25.0%] of 52, P = 0.04). These effects of prior
      syphilis remained after controlling for education and premorbid intelligence.

PMID- 23970702
TI  - HIV, hepatitis and syphilis prevalence and correlates of condom use during anal
      sex among men who have sex with men in the Republic of Moldova.
AB  - Limited data on HIV prevalence and related risks among men who have sex with men
      (MSM) exist in the Republic of Moldova. In Chisinau and Balti, 188 and 209,
      respectively, men who reported having anal or oral sex in the last six months
      with another man, aged >=16 years were recruited into a study in 2010 using
      respondent-driven sampling methods. MSM reported having multiple male and female
      partners and inconsistent condom use. In Chisinau, 2% of MSM were HIV
      seropositive, 3.7% had antibodies to hepatitis C (HCV), 5.7% had antibodies to
      hepatitis B (HBV) and 12.1% had syphilis. In Balti, less than 1% of MSM were HIV
      seropositive, 1.2% had antibodies to HCV, 3.2% had antibodies to HBV and only
      0.5% had syphilis. MSM who used a condom at last anal sex with a man were less
      likely to reside in Chisinau, to have casual sex partners and to have had an HIV
      test in the last year and were more likely to know where to get an HIV test.
      Although HIV prevalence was low, MSM practice a number of risky sexual behaviours
      that may heighten the risk of further HIV transmission in this population and to
      the wider population.

PMID- 23970703
TI  - Assessing the quality of HIV/AIDS services at military health facilities in
      Zambia.
AB  - After rapidly scaling up HIV/AIDS-related health services, the Zambian Defence
      Force (ZDF) has become concerned with assuring their quality. This evaluation
      assesses provider performance at eight ZDF facilities based on direct
      observations of 191 antenatal care (ANC) consultations and 175 follow-up
      consultations for antiretroviral therapy (ART). In addition, 43 ZDF health
      providers were interviewed about the work environment and service quality. On-the
      job performance varied widely: providers completed as few as 0% and as many as
      100% of tasks associated with each performance standard. Overall scores averaged
      66% (range: 47-93%) for ANC consultations and 60% (range: 37-100%) for ART
      consultations. Perceptions of the work environment were generally positive, but
      57% of providers lack confidence in their clinical skills and 42% think staffing
      is insufficient. These findings, which point to the unique opportunities and
      challenges in the military setting, will be used to guide a quality improvement
      initiative.

PMID- 23970704
TI  - Use of expedited partner therapy among chlamydia cases diagnosed at an urban
      Indian health centre, Arizona.
AB  - Chlamydia cases diagnosed in the women's clinic were more likely to receive
      expedited partner therapy (EPT) and to be re-tested as compared with urgent and
      emergent care settings. Fewer re-infections occurred among patients who received
      EPT. Disproportionate rates of chlamydia occur among American Indian (AI)
      populations. To describe use of EPT among chlamydia cases diagnosed at an urban
      Indian Health Service (IHS) facility in Arizona, health records were used to
      extract confirmed cases of chlamydia diagnosed between January 2009 and August
      2011. Medical records of 492 patients diagnosed with chlamydia were reviewed.
      Among the 472 cases who received treatment, 246 (52%) received EPT. Receipt of
      EPT was significantly associated with being female (odds ratio (OR) 2.1, 1.03
      4.4, P < 0.001) and receipt of care in the women's clinic (OR 9.9, 95% CI 6.0
      16.2) or in a primary care clinic (OR 2.4, 95% CI 1.1-5.1). Compared with those
      receiving care in the women's clinic, the odds of receipt of EPT were
      significantly less in those attending the urgent/express care clinic (OR 0.1, 95%
      CI 0.06-0.2), and the emergency department (OR 0.1, 95% CI 0.05-0.2). Among
      treated patients who underwent re-testing (N = 323, 68% total treated) re
      infection was less common among those that received EPT (13% versus 27%; OR 0.5,
      95% CI 0.3-0.9). In this IHS facility, EPT was protective in preventing chlamydia
      re-infection. Opportunities to expand the use of EPT were identified in urgent
      and emergent care settings.

PMID- 23970705
TI  - Determinants of generalized herpes simplex virus-2 epidemics: the role of sexual
      partner concurrency.
AB  - Little is known as to why some populations develop generalized herpes simplex
      virus 2 (HSV-2) epidemics. Sexual network-level factors, such as the proportion
      of partnerships that run concurrently, are plausible explanations. In this
      ecological analysis, we used Spearman's correlation coefficients to assess if
      there is an association between population prevalence of point-concurrency and
      HSV-2 in a number of national and subnational populations. We found that there is
      an association between prevalence of point-concurrency and female HSV-2
      prevalence between different countries (Spearman's rho = 0.715; P = 0.020), and
      within different races and ethnic groups within countries. In addition, there was
      a strong association between peak HIV and HSV-2 prevalence in 40-44-year-old
      women at an international level (Spearman's rho = 0.720; P = 0.0001). This could
      be indicative of populations with high HIV and HSV-2 prevalence rates having
      extensively connected sexual networks which puts them at increased risk of spread
      by both these sexually transmitted infections (STIs). No country with an HSV-2
      prevalence of under 20% in their 20-24-year-old women had a generalized HIV
      epidemic. Thus, HSV-2 prevalence in adolescents may be a useful marker of how
      risky a local sexual network is for STI spread and may provide a useful early
      indicator of the success or failure of behavior change initiatives.

PMID- 23970706
TI  - Specialty and Associate Specialist doctors: still the dependable backbone of
      genitourinary medicine.
AB  - Workforce planning is an inexact science. Specialty and Associate Specialist
      (SAS) doctors are rarely included in workforce analyses. Past studies have shown
      that SAS doctors are significant contributors to the work in genitourinary (GU)
      medicine clinics. This survey confirms the large amount of clinical work
      undertaken by SAS doctors. It appears that 51% of SAS doctors in GU plan to
      retire in the next 15 years and it is uncertain what effect the 2008 SAS contract
      will have on SAS recruitment. This information should be taken into consideration
      in future GUM workforce planning.

PMID- 23970707
TI  - A case-control pilot study on cognitive functioning, symptom validity and
      psychological wellbeing in HIV-1-infected patients in the Netherlands.
AB  - The objective of this study was to examine and relate both cognitive functioning
      and psychological wellbeing in Dutch HIV-1-infected patients (n = 30) in
      comparison with a matched healthy control group (n = 30), taking symptom validity
      into account. Significant differences in performance between patients and
      controls were found in the domain Working memory (P = 0.036), but not in the
      other cognitive domains. There was a significant difference in all dimensions of
      the psychological wellbeing scale, measured with the SCL-90-R (P values between
      0.002 and 0.023), except for agoraphobia, cognitive performance difficulty and
      sleep disturbances. No correlations were found between the performance on the
      Working memory domain and wellbeing. Future research should focus on unravelling
      the underlying mechanisms of neurocognitive dysfunction further using
      neuropsychological tests, including a symptom validity test in combination with
      neuroimaging techniques in larger samples.

PMID- 23970708
TI  - Non-occupational post-exposure prophylaxis for HIV at St Michael's Hospital,
      Toronto: a retrospective review of patient eligibility and clinical outcomes.
AB  - Stringent eligibility criteria, drug costs and antiretroviral toxicities are
      challenges in delivering HIV non-occupational post-exposure prophylaxis (nPEP).
      We reviewed patients' nPEP eligibility and clinical outcomes at St Michael's
      Hospital, Toronto, Canada to identify opportunities for improvement. Of 241
      patients, 59%, 36% and 6% presented for high- (receptive anal/vaginal, blood),
      medium- (insertive anal/vaginal) and low-risk (oral) sexual exposures,
      respectively, and nearly all (93%) presented within 72 hours. Of 205 patients
      given nPEP, 20 were known to have discontinued nPEP prematurely: three due to
      costs but none due to toxicities. Two HIV seroconversions occurred in patients
      with suspected ongoing potential exposures. Five asymptomatic syphilis diagnoses
      were made among 71 tested. Only 39% and 19% of nPEP patients returned to our
      institution for follow-up at 3-4 and six months, respectively. Our findings
      underscore the feasibility and importance of nPEP programmes to HIV and sexually
      transmitted infection control, while identifying opportunities for improvement.

PMID- 23970709
TI  - An audit of pharyngeal gonorrhoea treatment in a public sexual health clinic in
      Adelaide, South Australia.
AB  - In recent times there have been changes to guidelines regarding the management of
      gonorrhoea, from both the Centers for Disease Control and Prevention in 2010 and
      the British Association for Sexual Health and HIV (BASHH) in 2011. Coinciding
      with their release we conducted a clinical audit of our treatment protocol for
      gonorrhoea. In 2010, local data on the minimum inhibitory concentrations for
      Neisseria gonorrhoeae indicated an increase in local isolates that were less
      sensitive to ceftriaxone (11.6% c.f. 5.3% in 2009). We have a long history of
      using 250 mg of ceftriaxone to treat all standard sites of gonorrhoea infection
      followed with tests of cure in all cases. In a retrospective clinical audit of an
      11-year period from 2000 up to and including 2010 we identified six test-of-cure
      failures over 11 years after treating a total of 215 patients with pharyngeal
      gonorrhoea.

PMID- 23970710
TI  - Factors associated with the anonymous reporting of lifetime domestic violence in
      a genitourinary medicine clinic: a patient self-reported questionnaire study.
AB  - Domestic violence (DV) occurs frequently within the UK, with one in four women
      and one in six men experiencing DV during their life. DV is the leading cause of
      morbidity for women aged 19-44 years and is associated with sexual health
      problems. However, few data exist on the prevalence of DV in UK genitourinary
      (GU) medicine settings. An anonymous questionnaire was self-completed by patients
      (n = 476/500) attending Bournemouth GU medicine clinic during July 2009 to
      explore associations between lifetime DV and sociodemographic, sexual and
      behavioural factors. Overall, 21% (98/472) reported that they had ever been
      abused by a partner (12% [27/229] of men and 29% [71/243] of women). Logistic
      regression highlighted that being female, having children/dependants and use of
      illicit drugs were the most important factors associated with lifetime DV.
      Regular staff training on DV is recommended to increase awareness and signposting
      to relevant services.

PMID- 23970711
TI  - Internalized homonegativity/homophobia is associated with HIV-risk behaviours
      among Ugandan gay and bisexual men.
AB  - We investigated the relationship of internalized homonegativity/homophobia (IH)
      to sexual risk behaviours among 216 Ugandan gay and bisexual men, using the 7
      item IH scale previously developed on this population. IH was significantly
      associated with unprotected anal intercourse, and more so with unprotected
      receptive anal intercourse. Higher IH was also associated with more sex while
      intoxicated. There was a strong association between anal intercourse of any type
      and IH, suggesting a complex relationship between anal sex and identification
      with, or internalization of, homonegativity/homophobia. Specifically, it may be
      the anal component of sex rather than the sex with another man that is seen as
      labeling one as homosexual or stigmatizing. Those men who stated that they
      engaged in sex with other men for love, rather than for the physical feeling or
      for money, had higher IH scores. These data suggest that there may be an
      interactive relationship between IH and sexual behaviour, with greater
      internalization being associated with more stereotypically gay activities, which
      in turn may lead to more self-identification as gay and thus greater
      susceptibility to internalization.

PMID- 23970712
TI  - The great mimic: syphilis mimicking testicular tumour. Conservative management
      using antibiotics alone with testicular sparing.
AB  - We present the case of a 47-year-old man who attended a genitourinary (GU)
      medicine clinic with posthitis and a painless testicular mass on examination.
      Initial ultrasound revealed a 2-cm well-defined hypoechoic mass within the right
      testis and he was referred to urology on suspicion of malignancy. Subsequent
      syphilis serology was positive and the penile lesion and testicular mass were
      felt to be consistent with syphilis. After liaising with the urology department,
      and in view of negative tumour markers (lactate dehydrogenase, alfa-fetoprotein
      and human chorionic gonadotrophin) and known penicillin allergy, he was managed
      conservatively with four weeks of oral doxycycline. Follow-up ultrasound scans
      revealed adequate response of the testicular mass, with the last scan, performed
      at 10 months post-treatment, showing complete resolution. This is the first
      documented case of conservative management of a testicular syphilitic lesion
      using antibiotics alone with testicular sparing.

PMID- 23970714
TI  - Learning about new therapies: phase 3 clinical studies--and beyond.

PMID- 23970715
TI  - Mechanisms and management of diabetic painful distal symmetrical polyneuropathy.
AB  - Although a number of the diabetic neuropathies may result in painful
      symptomatology, this review focuses on the most common: chronic sensorimotor
      distal symmetrical polyneuropathy (DSPN). It is estimated that 15-20% of diabetic
      patients may have painful DSPN, but not all of these will require therapy. In
      practice, the diagnosis of DSPN is a clinical one, whereas for longitudinal
      studies and clinical trials, quantitative sensory testing and
      electrophysiological assessment are usually necessary. A number of simple numeric
      rating scales are available to assess the frequency and severity of neuropathic
      pain. Although the exact pathophysiological processes that result in diabetic
      neuropathic pain remain enigmatic, both peripheral and central mechanisms have
      been implicated, and extend from altered channel function in peripheral nerve
      through enhanced spinal processing and changes in many higher centers. A number
      of pharmacological agents have proven efficacy in painful DSPN, but all are prone
      to side effects, and none impact the underlying pathophysiological abnormalities
      because they are only symptomatic therapy. The two first-line therapies approved
      by regulatory authorities for painful neuropathy are duloxetine and pregabalin.
      alpha-Lipoic acid, an antioxidant and pathogenic therapy, has evidence of
      efficacy but is not licensed in the U.S. and several European countries. All
      patients with DSPN are at increased risk of foot ulceration and require foot
      care, education, and if possible, regular podiatry assessment. 

PMID- 23970718
TI  - Difficult management of glucose homeostasis in a 21-month-old child with type 1
      diabetes and unknown glutaric aciduria type I: a case report.

PMID- 23970719
TI  - Cardiovascular biomarkers, cardiac dysfunction, and outcomes in patients with
      type 2 diabetes: a prospective, multicenter study.

PMID- 23970716
TI  - Inpatient management of diabetic foot disorders: a clinical guide.
AB  - The implementation of an inpatient diabetic foot service should be the goal of
      all institutions that care for patients with diabetes. The objectives of this
      team are to prevent problems in patients while hospitalized, provide curative
      measures for patients admitted with diabetic foot disorders, and optimize the
      transition from inpatient to outpatient care. Essential skills that are required
      for an inpatient team include the ability to stage a foot wound, assess for
      peripheral vascular disease, neuropathy, wound infection, and the need for
      debridement; appropriately culture a wound and select antibiotic therapy;
      provide, directly or indirectly, for optimal metabolic control; and implement
      effective discharge planning to prevent a recurrence. Diabetic foot ulcers may be
      present in patients who are admitted for nonfoot problems, and these ulcers
      should be evaluated by the diabetic foot team during the hospitalization.
      Pathways should be in place for urgent or emergent treatment of diabetic foot
      infections and neuropathic fractures/dislocations. Surgeons involved with these
      patients should have knowledge and interest in limb preservation techniques.
      Prevention of iatrogenic foot complications, such as pressure sores of the heel,
      should be a priority in patients with diabetes who are admitted for any reason:
      all hospitalized diabetic patients require a clinical foot exam on admission to
      identify risk factors such as loss of sensation or ischemia. Appropriate
      posthospitalization monitoring to reduce the risk of reulceration and infection
      should be available, which should include optimal glycemic control and correction
      of any fluid and electrolyte disturbances.

PMID- 23970720
TI  - Impact of obesity on metabolic syndrome in Brazilian adolescents: a population
      based study.

PMID- 23970721
TI  - Gestational diabetes mellitus in HIV-infected and -uninfected pregnant women in
      Cameroon.

PMID- 23970722
TI  - Cardiometabolic risk in a rural Ugandan population.

PMID- 23970723
TI  - Global reality of type 1 diabetes care in 2013.

PMID- 23970724
TI  - neck circumference and insulin resistance in Chinese adults: the Cardiometabolic
      Risk in Chinese (CRC) Study.

PMID- 23970725
TI  - Improvement in insulin sensitivity during mifepristone treatment of Cushing
      syndrome: early and late effects.

PMID- 23970726
TI  - Fructose-induced hyperuricemia is associated with a decreased renal uric acid
      excretion in humans.

PMID- 23970727
TI  - Infection, absent tachycardia, cancer history, and severe coma are independent
      mortality predictors in geriatric patients with hyperglycemic crises.

PMID- 23970728
TI  - Neck circumference, carotid wall intima-media thickness, and incident stroke.

PMID- 23970729
TI  - Metformin and the incidence of cancer in patients with diabetes: a nested case
      control study.

PMID- 23970730
TI  - No difference in vitamin D levels between children newly diagnosed with type 1
      diabetes and their healthy siblings: a 13-year nationwide Danish study.

PMID- 23970731
TI  - Screening patients with type 2 diabetes for active tuberculosis in communities of
      China.

PMID- 23970732
TI  - Comment on: Lin et al. Long-term changes in adiposity and glycemic control are
      associated with past adenovirus infection. Diabetes Care 2013;36:701-707.

PMID- 23970733
TI  - Response to Comment on: Lin et al. Long-term changes in adiposity and glycemic
      control are associated with past adenovirus infection. Diabetes Care 2013;36:701
      707.

PMID- 23970734
TI  - Comment on: Au et al. Body composition is normal in term infants born to mothers
      with well-controlled gestational diabetes mellitus. Diabetes Care 2013;36:562
      564.

PMID- 23970735
TI  - Response to Comment on: Au et al. Body composition is normal in term infants born
      to mothers with well-controlled gestational diabetes mellitus. Diabetes Care
      2013;36:562-564.

PMID- 23970736
TI  - Comment on: Zhu et al. Fasting plasma glucose at 24-28 weeks to screen for
      gestational diabetes mellitus: new evidence from China. Diabetes Care
      2013;36:2038-2040.

PMID- 23970737
TI  - Response to Comment on: Zhu et al. Fasting plasma glucose at 24-28 weeks to
      screen for gestational diabetes mellitus: new evidence from China. Diabetes Care
      2013;36:2038-2040.

PMID- 23970738
TI  - Comment on: Kim et al. Prospective study of serum adiponectin and incident
      metabolic syndrome: the ARIRANG Study. Diabetes Care 2013;36:1547-1553.

PMID- 23970739
TI  - Response to Comment on: Kim et al. Prospective study of serum adiponectin and
      incident metabolic syndrome: the ARIRANG Study. Diabetes Care 2013;36:1547-1553.

PMID- 23970740
TI  - Implementing GRADE: calculating the risk difference from the baseline risk and
      the relative risk.
AB  - A key step in implementing the GRADE (Grading of Recommendations Assessment,
      Development and Evaluation) system is the estimation of a risk difference based
      on estimates of the baseline risk and the relative risk estimated from different
      sources. In this paper we describe a simple and effective method to calculate
      confidence intervals (CIs) for the risk difference for this situation. Whenever
      an independent source is available to estimate the baseline risk for the
      population to which the effect estimates should be applied, this source should be
      used and CIs for the absolute risk difference should be calculated taking all
      sources of uncertainty into account. 

PMID- 23970741
TI  - The 2012 International Union against Sexually Transmitted Infections European
      Collaborative Clinical Group report on the diagnosis and management of Neisseria
      gonorrhoeae infections in Europe.
AB  - The European Collaborative Clinical Group (ECCG) was inaugurated at the 26th
      International Union against Sexually Transmitted Infections (IUSTI) Congress in
      Riga, Latvia 2011. The ECCG is a network of over 100 sexually transmitted
      infection specialists who have come together to conduct questionnaire-based
      research across the European region. It is expected that this work will focus and
      direct guideline development. A central core group of the ECCG has also been
      established who are responsible for identifying suitable survey questions that
      will be carried out but only after approval by the full ECCG Board. The ECCG aims
      to conduct a maximum of two projects per year which will be presented at the
      annual regional congresses and published as appropriate.

PMID- 23970742
TI  - Does the '2012 IUSTI ECCG report on the diagnosis and management of Neisseria
      gonorrhoeae infections in Europe' depict the situation in Europe?
AB  - Gonorrhoea is a major public health concern globally. Of particular grave concern
      is that resistance to the third generation cephalosporins has been identified
      during recent years. This paper summarises and discusses the results of the '2012
      IUSTI European Collaborative Clinical Group (ECCG) report on the diagnosis and
      management of Neisseria gonorrhoeae infections in Europe'. Although high quality
      care was reported in many settings, in several other countries the testing,
      diagnostics, antimicrobial treatment and follow-up of gonorrhoea patients need to
      be optimized. This, together with increased access to and use of antimicrobial
      susceptibility testing, is crucial in controlling the emergent spread of
      cephalosporin-resistant and multidrug-resistant gonorrhoea.

PMID- 23970743
TI  - Factors affecting antiretroviral therapy adherence among HIV-positive pregnant
      and postpartum women: an adapted systematic review.
AB  - Adherence to antiretroviral therapy (ART) is crucial for effective treatment, but
      can be quite complex. Non-adherence can adversely affect treatment outcomes.
      Although many studies have been done on adherence in the general population, few
      have included HIV-positive pregnant and postpartum women in resource-constrained
      settings. This review assessed the evidence on adherence among these groups of
      women. A systematic search of databases was completed between June and July 2011.
      Both qualitative and quantitative studies were included. Eighteen studies from a
      total of 6622 satisfied the inclusion criteria that included inter alia
      facilitators and barriers to adherence. This review highlighted that there is
      still no consensus on the definition and measurement of adherence; also multiple
      factors can affect a woman's ability to adhere to ART. Some of the barriers and
      facilitators identified were similar in both the type of study (qualitative and
      quantitative) and among the various countries. Findings indicated that the few
      studies in this population are conducted primarily in resource-rich settings.
      Such paucity of information warrants urgent attention; thus targeted research is
      needed to provide insight on adherence within this population.

PMID- 23970744
TI  - Providers' lack of knowledge about herpes zoster in HIV-infected patients is
      among barriers to herpes zoster vaccination.
AB  - Identification of perceptions about herpes zoster (HZ) disease, vaccine
      effectiveness and safety, and vaccine recommendations may impact immunization
      practices of physicians for HIV-infected patients. A survey was used to quantify
      knowledge of HZ as well as determine physician immunization perceptions and
      practices. There were 272/1700 respondents (16%). Correct answers for the
      incidence of varicella zoster virus (VZV) infection in adults and incidence of HZ
      in HIV-infected patients were recorded by 14% and 10% of providers, respectively.
      Providers reported poor knowledge of the incidence of disease recurrence in HIV
      infected patients (41% correct), potency of HZ vaccine (47.5% correct) and
      mechanism of protection against reactivation of VZV (66% correct). Most (88%)
      agreed that HZ was a serious disease, and 73% believed that the burden of disease
      made vaccination important. A majority (75%) did not vaccinate HIV patients with
      HZ vaccine regardless of antiretroviral therapy status. Barriers to
      administration included safety concerns, concern that vaccine would not prevent
      HZ, risk of HZ dissemination, reimbursement issues and lack of Infectious
      Diseases Society of America (IDSA) guidelines. Only 38% of providers agreed that
      CDC guidelines were clear and 50% believed that clinical trials were needed prior
      to use of HZ vaccine in HIV-infected patients. Education about HZ is needed among
      HIV providers. Providers perceived vaccination as important, but data on vaccine
      safety and clear guidance from the CDC on this issue are lacking.

PMID- 23970745
TI  - Herpes simplex virus type 2 incidence and associated risk factors among female
      sex workers in a high HIV-prevalence area of China.
AB  - Herpes simplex virus type 2 (HSV-2) can contribute to the spread of HIV. From
      March 2006 to November 2009, female sex workers (FSWs) in Yunnan, China were
      recruited into an open cohort study to determine incidence and risk factors for
      HSV-2 acquisition. Participants were interviewed and tested for HSV-2 and other
      sexually transmitted infections (STIs) every six months. A multivariate Cox
      proportional hazards regression model with time-dependent variables was used to
      measure associations with HSV-2 acquisition. In 3.5 years, 83 incident cases of
      HSV-2 infection were diagnosed, yielding an overall incidence of 21.9 per 100
      person years (PY) (95% confidence interval [CI], 17.8-26.3). Working in higher
      risk commercial sex venues, current Neisseria gonorrhoeae infection, age of
      sexual debut <18 years and lack of a regular sex partner were independent factors
      associated with HSV-2 acquisition. The high incidence of HSV-2 suggests that
      prevention methods for HIV/STI control are urgently needed.

PMID- 23970746
TI  - Genital streptococcal infection in non-pregnant women: a case-note review.
AB  - The purpose of this case-note review was to examine the clinical features and
      management of women with either vulval or vaginal swabs culturing positive for
      streptococci. Group B haemolytic streptococcus was isolated in all cases. The
      majority of women with vulval streptococci presented with irritation or soreness.
      Candidal infection was found in 43% and a dermatosis in 27%. All women with
      positive vaginal culture had vaginal soreness and/or discharge. Candida was
      isolated in 27% and there were features of desquamative vaginitis in 20%. Women
      treated with erythromycin failed to improve symptomatically. The findings of this
      study suggest that streptococci mostly play a secondary role and colonize an
      already damaged genital epithelium.

PMID- 23970747
TI  - Screening HIV-infected adults in Malawi for anaemia: impact on eligibility for
      antiretroviral therapy.
AB  - Clinical staging determines antiretroviral therapy (ART) eligibility when CD4
      count is not available. Haemoglobin (Hb) <=8 g/dL is an indication for the
      treatment. We measured Hb in HIV-positive Malawian adults undergoing clinical
      assessment for ART eligibility and calculated the percentage of patients with CD4
      <= 350 cells/MUL deemed eligible for ART by clinical staging with and without Hb
      measurement, using the existing threshold and an alternative proposed after
      comparing Hb values to CD4 counts. Three hundred and thirty-eight patients had
      CD4 counts measured and 226 (67%) had CD4 <= 350 cells/MUL. Thirty-six (16%)
      patients with low CD4 count were eligible for ART by clinical assessment alone,
      48 (21%) when Hb was also measured with a threshold of <=8 g/dL and 74 (34%) with
      a threshold of <=10 g/dL. Measuring Hb alongside clinical assessment could
      increase the number of patients with CD4 <= 350 cells/MUL starting ART by 33%
      using a threshold of Hb <= 8 g/dL or 114% with a threshold of <=10g/dL.

PMID- 23970748
TI  - Women's preferences for testing and management of sexually transmitted infections
      among low-income New York City family planning clients.
AB  - High prevalence of chlamydia in the USA persists despite efforts to annually
      screen women under the age of 26. Tailoring sexually transmitted infection (STI)
      services to client preferences may strengthen existing programmes. We report
      women's preferences for STI services from a family planning clinic in New York
      City serving low-income women. Seventy-eight percent (995/1275) of eligible women
      participated, with a mean age of 26 (SD+/-7). Ninety-one percent self-identified
      as Latina. Nineteen percent reported a past STI. Women preferred self-collection
      (65%) for testing to a speculum exam (20%); 15% had no preference. Women with a
      previous STI were more likely to prefer a pelvic exam to women with no previous
      STI (50% versus 32%, P < 0.01). Nearly all women (94%) preferred informing a sex
      partner about a positive STI test themselves, but 88% were willing to bring
      expedited partner therapy to a partner. Women were more likely to prefer third
      party partner notification if their last partner was casual rather than a main
      partner (14% versus 3%, respectively, P < 0.01). Forty-four percent of
      participants worried about physical violence after partner notification. Self
      collecting specimens for screening was widely acceptable. Partner notification
      strategies should be based on understanding partnership status, including fears
      of violence.

PMID- 23970749
TI  - Liver function test abnormalities in Nigerian patients with human
      immunodeficiency virus and hepatitis B virus co-infection.
AB  - Data on baseline hepatic function of HIV and hepatitis B virus (HBV) co-infected
      patients are limited in sub-Saharan Africa. We assessed liver function test (LFT)
      abnormalities in Nigerian patients with HIV/HBV co-infection to highlight the
      impact of HIV on HBV-related liver disease in sub-Saharan Africa. A cross
      sectional study involving 100 HIV/HBV co-infected patients and 100 age- and sex
      matched HBV mono-infected controls. Blood testing for HIV antibodies, CD4+ cell
      count, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), LFTs,
      platelet count, fasting blood glucose and lipid profile were carried out. Non
      invasive hepatic fibrosis scores (aspartate aminotransferase-platelet ratio index
      [APRI] and FIB-4) were also calculated. Co-infected patients had deranged liver
      enzymes more than the controls (77% versus 64%, P = 0.04). The predominant
      patterns of enzyme derangement in co-infected patients were either predominantly
      ?ALP (30% versus 4%, P < 0.0001) or mixed (30% versus 15%, P = 0.01) but
      predominantly ?AST/ALT in the controls (25% versus 9%, P = 0.003). Co-infected
      patients had higher fibrosis scores for both APRI (P = 0.002) and FIB-4 (P =
      0.0001). On further analysis, LFT abnormalities and fibrosis scores were only
      significantly higher in co-infected patients in the immune clearance and HBeAg
      negative chronic hepatitis phases. LFT abnormalities are common in Nigerians with
      HBV infection and co-infection with HIV negatively impacts on hepatic function.

PMID- 23970750
TI  - Presentation of clinically suspected persistent chlamydial infection: a case
      series.
AB  - In vivo antimicrobial resistance has yet to be documented in Chlamydia
      trachomatis; however, there have been anecdotal reports of persistent infection.
      The purpose of this case series was to describe a group of patients who have
      persistent chlamydia infection despite adequate treatment and where re-infection
      was considered unlikely. Patients were selected using a clinical questionnaire.
      For inclusion patients had to have tested positive for C. trachomatis, at least
      twice, using a nucleic acid amplification test despite having been fully
      compliant with at least two rounds of recommended therapy and be deemed to be at
      low risk of re-infection. Patients were grouped into categories based on sexual
      behaviour. Twenty-eight patients are included in this case series; 46% declared
      no sexual contact since initial diagnosis (category 1), a further 36% declaring
      contact that was considered low risk of re-infection (categories 2-4); 61% showed
      signs and symptoms at initial presentation increasing to 75% at re-attendance.
      Thirty-nine percent of patients received azithromycin only while 48% received
      doxycycline also. This case series identifies patients with persistent chlamydia
      despite receiving treatment. There is a need for a case definition of clinical
      treatment failure, development of susceptibility testing methods and guidance on
      appropriate treatment for patients with persistent infection.

PMID- 23970751
TI  - Use of the UriSwab collection device for testing of Chlamydia trachomatis and
      Neisseria gonorrhoeae: implications for a postal testing service.
AB  - In order to demonstrate the reliability of UriSwab, a trial was conducted using
      urine samples that had previously returned a detected result for Chlamydia
      trachomatis and/or Neisseria gonorrhoeae. Urine specimens (115 samples) were
      received from sexual health clinics and tested using the Roche Cobas 4800 CT/NG
      method. Concurrently, the urine samples were pipetted directly on to the sponge
      applicator of the UriSwab, simulating micturition, and the urine harvested from
      the UriSwab was tested using the Roche Cobas 4800 method. Of the 87 standard
      urine specimens that were C. trachomatis detected, 85 (98%) were also detected in
      the corresponding UriSwab specimen (sensitivity 97.7%, specificity 95.7%). Of the
      34 standard specimens that were N. gonorrhoeae detected, 33 (97%) were also
      detected in the corresponding UriSwab specimen (sensitivity 97.1%, specificity
      100%). The performance of the UriSwab in this trial was comparable with the
      testing of neat first-catch urine specimens for both C. trachomatis and N.
      gonorrhoeae.

PMID- 23970752
TI  - British Association for Sexual Health and HIV Scottish investigation 2010-2011:
      reasons for non-attendance in individuals lost to follow-up for HIV care for more
      than 12 months in Scotland.
AB  - As of 31 March 2011, 6696 HIV diagnoses had ever been reported in Scotland; of
      these, 1791 individuals had died, 3339 were attending specialist services, but
      the remainder had defaulted from specialist care; an investigation into their
      reasons for non-attendance, and the efforts of services to re-engage, was
      undertaken by British Association for Sexual Health and HIV Scottish branch using
      a web-based survey questionnaire. Twelve of the 13 Scottish HIV services returned
      information for 424 of 579 eligible cases; 112 of these 424 individuals were
      identified as genuine non-attendees. Findings indicate that the epidemiology of
      these non-attendees is similar to that of the whole Scottish HIV cohort. Three
      quarters of individuals failed to attend a booked appointment following their
      last known attendance and very few attempts to contact non-attending individuals
      were successful. This survey has refocused attention on those lost to follow-up,
      while quality of the national data-set has improved, providing a clearer
      epidemiological picture of people living with HIV in Scotland.

PMID- 23970753
TI  - Mycobacterium arupense infection in HIV-infected patients from Iran.
AB  - Here we report two cases of infection caused by Mycobacterium arupense in HIV
      infected patients who had received Mycobacterium avium complex medication after
      primary treatment with antituberculous drugs. The causative agents were isolated
      from the respiratory and blood specimens of the patients. The identification was
      based on conventional and molecular tests. Our study provides further evidence on
      the role of this microorganism in clinical cases.

PMID- 23970754
TI  - Encephalitis in primary HIV infection: challenges in diagnosis and treatment.
AB  - We report a case of primary HIV encephalitis, which initially presented as acute
      psychosis. Magnetic resonance imaging of the brain was suggestive of vasculitis
      and multiple infarctions, whereas a brain biopsy after six weeks of symptoms
      showed HIV encephalitis with microglial nodules, but no signs of vasculitis. We
      review previous reported cases and radiological findings in HIV encephalitis and
      discuss the role of antiretroviral therapy and steroids in its management.

PMID- 23970755
TI  - Lymphogranuloma venereum detected from the pharynx in four London men who have
      sex with men.
AB  - Lymphogranuloma venereum (LGV) is an established cause of proctitis in men who
      have sex with men (MSM). Currently in the UK, testing for pharyngeal Chlamydia
      trachomatis (CT) is not routine, and LGV typing is usually only performed in
      patients with anorectal symptoms. We report four cases where LGV-associated CT
      DNA was detected from the pharynx in MSM, demonstrating that nucleic acid
      amplification testing (NAAT) can be used for detecting and typing pharyngeal CT
      infection. These cases also highlight other possible routes of infection for LGV,
      and add to the broad spectrum of clinical presentations associated with this
      infection.

PMID- 23970756
TI  - Acute pulmonary embolism being the first presentation of undetected HIV
      infection: report of two cases.
AB  - Though HIV infection is considered as a hypercoagulable state, but occurrence of
      acute pulmonary embolism (PE) is rare and usually seen in the advanced stage of
      the disease. PE as a presentation in a case where there is no previous history of
      having HIV infection is very rare; a Medline search revealed only one case
      reported previously. We describe two cases who presented with acute PE and were
      treated; they were subsequently diagnosed as having HIV infection.

PMID- 23970757
TI  - False-positive prostate cancer markers in a man with symptomatic urethral
      Chlamydia trachomatis infection.
AB  - Symptomatic male urethral Chlamydia trachomatis infection resulted in
      inflammation of the prostate, with associated increases in both prostate-specific
      (PSA) and prostate cancer-specific (PCA3) markers with prostate biopsies showing
      no evidence of malignancy.

PMID- 23970758
TI  - Why do men who have sex with men and who are at high risk of HIV infection,
      decline HIV testing?

PMID- 23970759
TI  - Primary syphilitic chancres on arms, fingers and hands: more common than
      reported.

PMID- 23970760
TI  - Family history of REM sleep behaviour disorder more common in individuals
      affected by the disorder than among unaffected individuals.

PMID- 23970761
TI  - Thyroid hormone, thyromimetics, and metabolic efficiency.
AB  - Thyroid hormone (TH) has long been recognized as a major modulator of metabolic
      efficiency, energy expenditure, and thermogenesis. TH effects in regulating
      metabolic efficiency are transduced by controlling the coupling of mitochondrial
      oxidative phosphorylation and the cycling of extramitochondrial substrate/futile
      cycles. However, despite our present understanding of the genomic and nongenomic
      modes of action of TH, its control of mitochondrial coupling still remains
      elusive. This review summarizes historical and up-to-date findings concerned with
      TH regulation of metabolic energetics, while integrating its genomic and
      mitochondrial activities. It underscores the role played by TH-induced gating of
      the mitochondrial permeability transition pore (PTP) in controlling metabolic
      efficiency. PTP gating may offer a unified target for some TH pleiotropic
      activities and may serve as a novel target for synthetic functional thyromimetics
      designed to modulate metabolic efficiency. PTP gating by long-chain fatty acid
      analogs may serve as a model for such strategy. 

PMID- 23970762
TI  - Early-life glucocorticoid exposure: the hypothalamic-pituitary-adrenal axis,
      placental function, and long-term disease risk.
AB  - An adverse early-life environment is associated with long-term disease
      consequences. Adversity early in life is hypothesized to elicit developmental
      adaptations that serve to improve fetal and postnatal survival and prepare the
      organism for a particular range of postnatal environments. These processes,
      although adaptive in their nature, may later prove to be maladaptive or
      disadvantageous if the prenatal and postnatal environments are widely discrepant.
      The exposure of the fetus to elevated levels of either endogenous or synthetic
      glucocorticoids is one model of early-life adversity that contributes
      substantially to the propensity of developing disease. Moreover, early-life
      glucocorticoid exposure has direct clinical relevance because synthetic
      glucocorticoids are routinely used in the management of women at risk of early
      preterm birth. In this regard, reports of adverse events in human newborns have
      raised concerns about the safety of glucocorticoid treatment; synthetic
      glucocorticoids have detrimental effects on fetal growth and development,
      childhood cognition, and long-term behavioral outcomes. Experimental evidence
      supports a link between prenatal exposure to synthetic glucocorticoids and
      alterations in fetal development and changes in placental function, and many of
      these alterations appear to be permanent. Because the placenta is the conduit
      between the maternal and fetal environments, it is likely that placental function
      plays a key role in mediating effects of fetal glucocorticoid exposure on
      hypothalamic-pituitary-adrenal axis development and long-term disease risk. Here
      we review recent insights into how the placenta responds to changes in the
      intrauterine glucocorticoid environment and discuss possible mechanisms by which
      the placenta mediates fetal hypothalamic-pituitary-adrenal development,
      metabolism, cardiovascular function, and reproduction. 

PMID- 23970763
TI  - Plaque disruption during transcatheter aortic valve replacement.

PMID- 23970764
TI  - The epidemiology of HIV infection in Morocco: systematic review and data
      synthesis.
AB  - Morocco has made significant strides in building its HIV research capacity. Based
      on a wealth of empirical data, the objective of this study was to conduct a
      comprehensive and systematic literature review and analytical synthesis of HIV
      epidemiological evidence in this country. Data were retrieved using three major
      sources of literature and data. HIV transmission dynamics were found to be
      focused in high-risk populations, with female sex workers (FSWs) and clients
      contributing the largest share of new HIV infections. There is a pattern of
      emerging epidemics among some high-risk populations, and some epidemics,
      particularly among FSWs, appear to be established and stable. The scale of the
      local HIV epidemics and populations affected show highly heterogeneous
      geographical distribution. To optimize the national HIV response, surveillance
      and prevention efforts need to be expanded among high-risk populations and in
      geographic settings where low intensity and possibly concentrated HIV epidemics
      are emerging or are already endemic.

PMID- 23970765
TI  - Use of the Alcohol Use Disorders Identification Test (AUDIT) to determine the
      prevalence of alcohol misuse among HIV-infected individuals.
AB  - The aim of the paper is to evaluate alcohol misuse among an inner city adult HIV
      clinic population with AUDIT (Alcohol Use Disorders Identification Test). A cross
      sectional HIV outpatient clinic analysis between 28 February 2011 and 11 March
      2011 was carried out. AUDIT, demographic and clinical data were collected.
      Univariate analysis was performed to look for the associations between variables.
      Backward stepwise multivariate analyses were performed on significant variables
      from the univariate analysis to assess for predictors of alcohol dependence. In
      total, 111 patients were included (60% uptake of clinic attendees); 66% were men
      and 26% were hepatitis C virus (HCV) co-infected. The median AUDIT score was 5
      (within normal range). Thirty-four 'AUDIT positive' cases were identified: five
      (4.5%) indicated consumption of hazardous levels of alcohol; 21 (19%) indicated
      harmful levels of alcohol; and eight (7%) were likely alcohol dependent. Younger
      age (<40 years old) was significantly associated with AUDIT positivity (P =
      0.006). On multivariate analysis younger age (P = 0.045, odds ratio 13.8) and
      lower level of education (P = 0.006, odds ratio 6.7) were predictive of scores
      indicative of alcohol dependence (AUDIT >=20). In conclusion, younger age and
      lower educational levels were associated with scores consistent with alcohol
      dependence. AUDIT was well tolerated and easy to administer in this outpatient
      HIV clinic population.

PMID- 23970766
TI  - The longitudinal association of venue stability with consistent condom use among
      female sex workers in two Mexico-USA border cities.
AB  - We examined the relationship between venue stability and consistent condom use
      (CCU) among female sex workers who inject drugs (FSW-IDUs; n = 584) and were
      enrolled in a behavioural intervention in two Mexico-USA border cities. Using a
      generalized estimating equation approach stratified by client type and city, we
      found venue stability affected CCU. In Tijuana, operating primarily indoors was
      significantly associated with a four-fold increase in the odds of CCU among
      regular clients (odds ratio [OR]: 3.77, 95% confidence interval [CI]: 1.44,
      9.89), and a seven-fold increase among casual clients (OR: 7.18, 95% CI: 2.32,
      22.21), relative to FSW-IDUs spending equal time between indoor and outdoor sex
      work venues. In Ciudad Juarez, the trajectory of CCU increased over time and was
      highest among those operating primarily indoors. Results from this analysis
      highlight the importance of considering local mobility, including venue type and
      venue stability, as these characteristics jointly influence HIV risk behaviours.

PMID- 23970767
TI  - Reported changes in sexual behaviour and human papillomavirus knowledge in
      Peruvian female sex workers following participation in a human papillomavirus
      vaccine trial.
AB  - Limited data exist on the effect of clinical trial participation on sexual
      behavioural change. Two hundred female sex workers working in Lima, Peru received
      human papillomavirus (HPV) vaccine in either the standard (0, 2, 6 months) or
      modified (0, 3, 6 months) schedule. Participants received comprehensive screening
      and treatment for sexually transmitted infections (STIs), counselling on safe sex
      practices, education about HPV and the HPV vaccine, contraceptives (oral and
      condoms) and family planning at each visit. We assessed vaccine completion rates,
      change in sexual practices, and changes in HPV knowledge before and after
      participation in the vaccine trial. There were high rates of vaccine completion,
      91% overall. The estimated number of reported new and total clients over a 30-day
      period decreased significantly (P < 0.001). Knowledge about HPV and HPV-related
      disease increased among all participants. In addition, all participants listed at
      least one preventive strategy during the month 7 follow-up survey.

PMID- 23970768
TI  - Biomarker evaluation of self-reported condom use among women in HIV-discordant
      couples.
AB  - Self-reported condom use is a commonly collected statistic, yet its use in
      research studies may be inaccurate. We evaluated this statistic among women in
      HIV-discordant couples enrolled in a clinical trial in Nairobi, Kenya. Vaginal
      swabs were acquired from 125 women and tested for prostate-specific antigen
      (PSA), a biomarker for semen exposure, using an enzyme-linked immunosorbent
      assay. Ten (10%) of 98 women who reported 100% use of condoms in the previous
      month tested PSA positive. In a bivariate logistic regression analysis, among
      women who reported 100% condom use in the previous month, those with <=8 years of
      school had significantly higher odds of testing PSA-positive (odds ratio [OR] =
      8.39, 95% confidence interval [CI] 1.02-69.13) than women with more schooling.
      Our estimate may be conservative, as the ability to detect PSA may be limited to
      24-48 hours after exposure. Less educated women may be a target group for
      counselling regarding reporting sexual behaviour in clinical trials.

PMID- 23970769
TI  - Factors associated with acceptability of circumcision among male drug users in
      western China: a cross-sectional study.
AB  - This study is aimed to investigate whether male circumcision (MC) is feasible
      among IDUs in China. 1304 drug users who attended methadone maintenance therapy
      clinics in Guangxi, Chongqing and Xinjiang were selected for participation by
      using convenience sampling, and completed a self-administered questionnaire. The
      factors associated with the acceptability of MC were examined via multiple
      logistic regression models. 45.2% (589/1304) of the participants reported an
      acceptance of MC. Many of the participants who were initially not willing to
      accept MC (715/1304) had changed their mind when they were informed that MC would
      reduce the risk of HIV and STDs (43.4%; 310/715), that MC is associated with few
      surgery-related complications (23.1%; 165/715), that the surgical procedure could
      be arranged free of charge (20.1%, 144/715). In the multivariate analysis, higher
      acceptability of MC was associated with knowledge of the hazards of phimosis
      (OR=2.22), the presence of phimosis (OR=14.87), and knowledge that MC can prevent
      AIDS and STDs (OR=1.49); while lower acceptability was associated with residing
      in Chongqing province (OR=0.41) and an educational level of junior (OR=0.64) and
      senior high (OR=0.63) school. The MC policy targeting IDUs in China should take
      into account these factors associated with MC acceptability.

PMID- 23970770
TI  - Effect of HIV genotypic drug resistance testing on the management and clinical
      course of HIV-infected children and adolescents.
AB  - The clinical utility of genotypic drug resistance testing (DRT) in HIV-infected
      children on antiretroviral therapy (ART) is not well understood. HIV-infected
      patients aged <19 years undergoing DRT for virological failure were
      retrospectively enrolled. Indications for DRT and changes in HIV RNA load were
      recorded. Between January 2000 and December 2006, 57 patients had DRT. The most
      common indication for DRT was poor ART adherence (57.7% of patients). ART was
      changed in 50.9% of patients after DRT. Poor adherence was cited by clinicians
      for not changing ART significantly more often than any other reason (47.3%, P <
      0.001). After DRT, significant improvement in HIV RNA load occurred independent
      of ART changes, though patients whose ART was modified were more likely to become
      undetectable (31.5% versus 7.0%, P < 0.001). Poor adherence was a significant
      factor for ordering DRT and for not changing ART in HIV-infected children.

PMID- 23970771
TI  - Correlates of consistent condom use among female entertainment workers in
      Shanghai, China: a repeated measures analysis.
AB  - Female entertainment workers (FEWs) in China are at increased risk of HIV and
      other sexually transmitted infections, but correlates of their risky sexual
      behaviour remain poorly understood. Using data from a series of four surveys,
      this paper employs repeated measures analysis to identify individual and social
      correlates of consistent condom use among FEWs in Shanghai. Results reveal that
      both individual cognitive and social influence factors are statistically
      significant in their bivariate relationships to consistent condom use with a
      stable or non-stable partner; only prevention motivation and perceived self
      efficacy in condom use remain significant in the multiple regressions. When
      individual and social correlates are examined together, only peer support for
      condom use remains a significant and independent correlate of consistent condom
      use in sex with a non-stable partner. Behavioural intervention is urgently needed
      and should take a multilevel approach, emphasizing individual prevention
      motivation and behavioural skills training and promoting peer/social support.

PMID- 23970772
TI  - Seroprevalence of hepatitis B in a cohort of HIV-infected children and adults in
      Swaziland.
AB  - Hepatitis B virus (HBV) is an important co-morbidity in the HIV epidemic. A
      retrospective chart review was performed of HIV-infected patients with no
      previous antiretroviral history enrolled in a Swaziland clinic from January 2009
      to May 2011. The seroprevalence of HBV surface antigen (HBsAg) was calculated and
      the data were analyzed using Mann-Whitney U and Fisher's exact tests. A total of
      1282 patients were included in analysis. Five hundred were children aged <15
      years. Overall HBsAg seroprevalence was 3.7% (1.4% of children and 5.1% of
      adults). Prevalence in under-5s was low (0.4%). Among adult women and men,
      prevalence was 4.2% and 9.8%, respectively (P = 0.022). Median alanine
      aminotransferase level was 19 U/L in the HBsAg-negative adults and 25 U/L in the
      HBsAg-positive adults (P = 0.005). Given the number of patients found to be HBsAg
      positive, especially among adults, it is important for antiretroviral programmes
      to consider universal screening and strategically utilize medications that have
      been found effective in treating both HBV and HIV.

PMID- 23970773
TI  - Human papillomavirus genotypes in genital warts in Latin America: a cross
      sectional study in Bogota, Colombia.
AB  - Epidemiological studies on benign lesions related to human papillomavirus (HPV)
      infection are scarce in Latin America. We enrolled 342 consecutive patients with
      lesions suspected of being genital warts (GW). All patients underwent
      confirmatory biopsy and GP5+/GP6+/- Reverse Line Blot HPV testing on frozen
      tissue. In 261 (81%) cases, the diagnosis was confirmed by histopathology and HPV
      was detected in 90.6% of men and 87.7% of women. HPV 6 was by far the most common
      type in both women (62%) and men (56%), followed by HPV 11 (~20%). Co-infection
      with these two types occurred in 7% and 12% of women and men, respectively. HPV16
      ranked third in prevalence, with 16% of patients testing positive. Twenty-five
      percent of cases tested positive for multiple HPV genotypes. Although HPV 6 and
      HPV 11 were the main types detected and no differences between men and women were
      observed, we found HPV 11 contributed more to GW aetiology compared with previous
      reports, showing a variability of HPV type distribution in GW across populations.
      This information is valuable baseline data in Latin America for future
      estimations of the burden of GW in men and women and shows the potential benefit
      obtainable by prophylactic vaccination against HPV types 6 and 11.

PMID- 23970774
TI  - A trial of questionnaire administration modalities for measures of sexual risk
      behaviour in the uniformed services of Peru.
AB  - Modalities of questionnaire administration may affect data quality, particularly
      when conducting Biological and Behavioral Surveillance Surveys (BBSS) of
      uniformed personnel. We aimed to examine differences in administration, reporting
      and data quality across several common modalities of administration for BBSS
      endeavors. Prior to a large-scale BBSS endeavor with the uniformed services of
      Peru, we pilot tested three modes of questionnaire administration among personnel
      engaged in internal combat: face-to-face interview (FFI), self-administered paper
      based interview (SAPI), and audio computer-assisted self-interview (ACASI).
      Individuals who took the survey using ACASI were less likely to have missing data
      on measures of sexual risk and alcohol abuse and were more likely to report
      sexual risk behaviours and symptoms of alcohol abuse; however, more individuals
      took the survey using SAPI given inadequate time to devote to sitting through an
      entire FFI or ACASI. Sexually transmitted infections did not vary significantly
      across modes of questionnaire administration. While more logistically complicated
      for BBSS efforts in resource-constrained settings, we recommend the use of ACASI
      in collecting BBSS data from uniformed personnel if conditions are permissible.

PMID- 23970775
TI  - Hypophosphataemia with non-tenofovir-containing antiretroviral therapy.
AB  - Hypophosphataemia with tenofovir (TDF) treatment has been well described. The
      role of HIV infection and of other antiretroviral (ART) agents in
      hypophosphataemia has received less attention. The aim of this study was to
      determine the prevalence of hypophosphataemia in HIV-positive adults. We measured
      the fasting plasma phosphate level and estimated glomerular filtration rate
      (eGFR) in 123 HIV-positive patients. A total of 26% had hypophosphataemia and 11%
      had hypophosphataemia of grades 2-4 (0.65 mmol/L or less). Hypophosphataemia of
      any grade was more frequent in those who were ART-treated than ART-naive (35%
      versus 10%; P = 0.0001). Multiple linear regression analysis showed no
      significant association between phosphate level and gender, TDF status, duration
      of ART, duration of HIV infection and eGFR. Increasing age was significantly
      associated with a very small rise in phosphate level. Isolated hypophosphataemia
      was significantly more frequent in HIV-positive subjects receiving ART than ART
      naive individuals, irrespective of the drug regimen.

PMID- 23970776
TI  - Central pontine myelinolysis in advanced HIV infection with tuberculosis and
      multicentric Castleman's disease.
AB  - We present a case of central pontine myelinolysis (CPM) in a patient with
      advanced HIV infection and miliary tuberculosis. While hospitalized the patient
      developed an unusual ataxic variant of CPM with full clinical recovery. Follow-up
      imaging revealed resolution of pontine lesions. To our knowledge, this is the
      first report of a clinical and radiological recovery from CPM in advanced HIV
      disease. Our report extends our knowledge of neurological presentations in
      patients with advanced HIV infection. It highlights the importance of considering
      CPM in patients with advanced HIV disease presenting with an ataxic syndrome,
      even in the absence of an electrolyte derangement.

PMID- 23970777
TI  - Penile intraepithelial neoplasia: important lessons from a case series.
AB  - Seven men presenting to our genitourinary (GU) medicine clinic over a period of
      22 months had a histopathological diagnosis of penile intraepithelial neoplasia
      (PIN). Median duration of symptoms was eight months (range 2-216 months).
      Macroscopic appearances were different in all cases. All histology was reviewed
      locally and at a tertiary centre. Six of seven had severe dysplasia (PIN III).
      Interestingly, only one individual was HIV-positive and one, who was
      immunocompetent, had multifocal disease. These cases highlight the importance of
      a full anogenital examination and early biopsy in patients presenting with
      atypical or persistent penile lesions.

PMID- 23970778
TI  - Primary cervical lymphoma: a rare presentation to a genitourinary medicine
      clinic.
AB  - Primary non-Hodgkin's lymphoma of uterine cervix is a rare diagnosis. We present
      the case of a 47-year-old woman who presented to our genitourinary (GU) medicine
      service complaining of a malodorous discharge. Speculum examination revealed a
      necrotic mass on the cervix. She was referred urgently to gynaecology and
      subsequent histology revealed a diffuse large B-cell lymphoma. She received six
      cycles of RCHOP chemotherapy and is now in clinical remission. This case
      highlights the need for GU medicine physicians to remain vigilant with regard to
      possible gynaecological malignancies in all of our patients, the need for medical
      backup within GU medicine clinics and for clear pathways of referral to other
      specialists to exist.

PMID- 23970779
TI  - Achieving rapid reduction of HIV-1 viral load in HIV-positive pregnant women
      close to term - an obstetric/medical emergency: a review of three cases.
AB  - Mother-to-child transmission (MTCT) of HIV infection is now uncommon in the UK
      and the management of HIV-positive pregnant women is usually relatively
      straightforward. However, HIV viral load suppression may be difficult to achieve
      peripartum for women who book very late in pregnancy and those with a poor
      adherence to antiretroviral therapy (ART). These pregnancies are at a higher risk
      of MTCT due to high viral load (VL). Therefore, the development of interventions
      to achieve a rapid reduction of HIV VL is essential. We describe three relevant
      cases that presented to our unit over a 12-month period and discuss the
      strategies employed to manage these challenging cases. All babies were born
      healthy and were HIV proviral DNA-negative at 12 weeks postpartum. No serious
      adverse events were reported for the mothers or their babies.

PMID- 23970780
TI  - Pseudoaneurysm associated with an arteriovesical fistula after bladder
      substitution surgery definitively treated with a covered stent: a report of 3
      cases.
AB  - A fistula between the iliac artery and a bladder pouch is a rare but potentially
      life-threatening condition. In 3 patients presenting with massive hematuria after
      urinary diversion, an iliac artery pseudoaneurysm was found on imaging studies.
      These pseudoaneurysms were considered to be associated with a fistula between
      artery and pouch, causing the hematuria. All patients were successfully treated
      with a covered stent to exclude the pseudoaneurysm and the arteriovesical
      fistula. Clinical follow-up of 10 weeks, 16 months, and 27 months, respectively,
      showed no residual hematuria. In addition, no clinical signs of stent graft
      infection or thrombosis were identified during follow-up. In conclusion, the
      placement of a covered stent is a valuable therapeutic treatment option in the
      management of hematuria due to an arteriovesical fistula after urinary diversion
      surgery. 

PMID- 23970781
TI  - Effect of zinc binding residues in growth hormone (GH) and altered intracellular
      zinc content on regulated GH secretion.
AB  - Endocrine cells store hormones in concentrated forms (aggregates) in dense-core
      secretory granules that are released upon appropriate stimulation. Zn(2+) binding
      to GH through amino acid residues His18, His21, and Glu174 are essential for GH
      dimerization and might mediate its aggregation and storage in secretory granules.
      To investigate whether GH-1 gene mutations at these positions interfere with this
      process, GH secretion and intracellular production were analyzed in GC cells (rat
      pituitary cell line) transiently expressing wt-GH and/or GH Zn mutant (GH-H18A
      H21A-E174A) in forskolin-stimulated vs nonstimulated conditions. Reduced
      secretion of the mutant variant (alone or coexpressed with wt-GH) compared with
      wt-GH after forskolin stimulation was observed, whereas an increased
      intracellular accumulation of GH Zn mutant vs wt-GH correlates with its altered
      extracellular secretion. Depleting Zn(2+) from culture medium using N,N,N',N'
      tetrakis(2-pyridylemethyl)ethylenediamine, a high-affinity Zn(2+) chelator, led
      to a significant reduction of the stimulated wt-GH secretion. Furthermore,
      externally added Zn(2+) to culture medium increased intracellular free Zn(2+)
      levels and recovered wt-GH secretion, suggesting its direct dependence on free
      Zn(2+) levels after forskolin stimulation. Confocal microscopy analysis of the
      intracellular secretory pathway of wt-GH and GH Zn mutant indicated that both
      variants pass through the regulated secretory pathway in a similar manner. Taken
      together, our data support the hypothesis that loss of affinity of GH to Zn(2+)
      as well as altering intracellular free Zn(2+) content may interfere with normal
      GH dimerization (aggregation) and storage of the mutant variant (alone or with wt
      GH), which could possibly explain impaired GH secretion. 

PMID- 23970782
TI  - Postnatal expression of BRAFV600E does not induce thyroid cancer in mouse models
      of thyroid papillary carcinoma.
AB  - The mutant BRAF (BRAF(V600E)) is the most common genetic alteration in papillary
      thyroid carcinomas (PTCs). The oncogenicity of this mutation has been shown by
      some genetically engineered mouse models. However, in these mice, BRAF(V600E) is
      expressed in all the thyroid cells from the fetal periods, and suppresses thyroid
      function, thereby leading to TSH elevation, which by itself promotes thyroid
      tumorigenesis. To overcome these problems, we exploited 2 different approaches,
      both of which allowed temporally and spatially restricted expression of
      BRAF(V600E) in the thyroid glands. First, we generated conditional transgenic
      mice harboring the loxP-neo(R)-loxP-BRAF(V600E)-internal ribosome entry site
      green fluorescent protein sequence [Tg(LNL-BRAF(V600E))]. The double transgenic
      mice (LNL-BRAF(V600E);TPO-Cre) were derived from a high expressor line of Tg(LNL
      BRAF(V600E)) mice and TPO-Cre mice; the latter expresses Cre DNA recombinase
      under the control of thyroid-specific thyroid peroxidase (TPO) promoter and
      developed PTC-like lesions in early life under normal serum TSH levels due to
      mosaic recombination. In contrast, injection of adenovirus expressing Cre under
      the control of another thyroid-specific thyroglobulin (Tg) promoter (Ad-TgP-Cre)
      into the thyroids of LNL-BRAF(V600E) mice did not induce tumor formation despite
      detection of BRAF(V600E) and pERK in a small fraction of thyroid cells. Second,
      postnatal expression of BRAF(V600E) in a small number of thyroid cells was also
      achieved by injecting the lentivirus expressing loxP-green fluorescent protein
      loxP-BRAF(V600E) into the thyroids of TPO-Cre mice; however, no tumor development
      was again observed. These results suggest that BRAF(V600E) does not appear to
      induce PTC-like lesions when expressed in a fraction of thyroid cells postnatally
      under normal TSH concentrations. 

PMID- 23970784
TI  - Testosterone protects against glucotoxicity-induced apoptosis of pancreatic beta
      cells (INS-1) and male mouse pancreatic islets.
AB  - Male hypogonadism associates with type 2 diabetes, and T can protect pancreatic
      beta-cells from glucotoxicity. However, the protective mechanism is still
      unclear. This study thus aims to examine the antiapoptotic mechanism of T in
      pancreatic beta cells cultured in high-glucose medium. T (0.0005-2 MUg/mL) was
      added to INS-1 cells cultured in basal glucose or high-glucose media. Then
      cellular apoptosis, oxidative stress, and cell viability were measured.
      Endoplasmic reticulum (ER) stress markers and sensors and the antiapoptotic
      protein (B-cell lymphoma 2) were investigated by real-time PCR and Western blot
      analysis. ER stress markers were also measured in male mouse pancreatic islet
      cultured in similar conditions. T (0.05 and 0.5 MUg/mL) did not have any effect
      on apoptosis and viability of INS-1 cells cultured in basal glucose medium, but
      it could reduce apoptosis and increase viability of INS-1 cells cultured in high
      glucose medium. The protective effect of T is diminished by androgen receptor
      inhibitor. T (0.05 MUg/mL) could significantly reduce nitrotyrosine levels, mRNA,
      and protein levels of the ER stress markers and sensor those that were induced
      when INS-1 cells were cultured in high-glucose medium. It could also
      significantly increase the survival proteins, sarco/endoplasmic reticulum Ca(2+)
      ATPase-2, and B-cell lymphoma 2 in INS-1 cells cultured in the same conditions.
      Similarly, it could reduce ER stress markers and increase sarco/endoplasmic
      reticulum Ca(2+) ATPase protein levels in male mouse pancreatic islets cultured
      in high-glucose medium. T can protect against male pancreatic beta-cell apoptosis
      from glucotoxicity via the reduction of both oxidative stress and ER stress. 

PMID- 23970783
TI  - Protein kinase D1 is essential for bone acquisition during pubertal growth.
AB  - Bone formation and maintenance represents the summation of the balance of local
      and endocrine hormonal stimuli within a complex organ. Protein kinase D (PKD) is
      a member of the Ca(2+)/calmodulin-dependent kinase superfamily of
      serine/threonine kinases and has been described as the crossroads for the bone
      morphogenetic protein (BMP)-IGF-I signaling axis, which plays a major role in
      bone formation. The current study exploits the PKD1-deficient mouse model to
      examine the role of PKD in vivo in the skeleton. Dual-energy x-ray absorptiometry
      scan analysis of male and female pubescent mice demonstrated significantly
      decreased bone mineral density in the whole body and femoral bone compartments of
      PKD1 (+/-) mice, compared with their wild-type littermates. The body weight,
      nasal-anal length, and percentage body fat of the mice were not significantly
      different from their wild-type littermates. Cultured bone marrow stromal cells
      from PKD1 (+/-) mice demonstrated lower alkaline phosphatase activity in early
      differentiating osteoblasts and decreased mineralized nodule formation in mature
      osteoblasts. Quantitative RT-PCR analysis of osteoblast differentiation markers
      and osteoclast markers exhibited lower levels of expression in PKD1 (+/-) male
      mice than wild type. In female mice, however, only markers of osteoblast
      differentiation were reduced. PKD1 (+/-) mice also demonstrated a profound
      reduction in mRNA expression levels of BMP type II receptor and IGF-I receptor
      and in BMP-7 responsiveness in vitro. Together these data suggest that in mice,
      PKD1 action contributes to the regulation of osteoblastogenesis by altering gene
      expression with gender-specific effects on osteoclastogenesis, subsequently
      affecting skeletal matrix acquisition during puberty. 

PMID- 23970785
TI  - GPER deficiency in male mice results in insulin resistance, dyslipidemia, and a
      proinflammatory state.
AB  - Estrogen is an important regulator of metabolic syndrome, a collection of
      abnormalities including obesity, insulin resistance/glucose intolerance,
      hypertension, dyslipidemia, and inflammation, which together lead to increased
      risk of cardiovascular disease and diabetes. The role of the G protein-coupled
      estrogen receptor (GPER/GPR30), particularly in males, in these pathologies
      remains unclear. We therefore sought to determine whether loss of GPER
      contributes to aspects of metabolic syndrome in male mice. Although 6-month-old
      male and female GPER knockout (KO) mice displayed increased body weight compared
      with wild-type littermates, only female GPER KO mice exhibited glucose
      intolerance at this age. Weight gain in male GPER KO mice was associated with
      increases in both visceral and sc fat. GPER KO mice, however, exhibited no
      differences in food intake or locomotor activity. One-year-old male GPER KO mice
      displayed an abnormal lipid profile with higher cholesterol and triglyceride
      levels. Fasting blood glucose levels remained normal, whereas insulin levels were
      elevated. Although insulin resistance was evident in GPER KO male mice from 6
      months onward, glucose intolerance was pronounced only at 18 months of age.
      Furthermore, by 2 years of age, a proinflammatory phenotype was evident, with
      increases in the proinflammatory and immunomodulatory cytokines IL-1beta, IL-6,
      IL-12, TNFalpha, monocyte chemotactic protein-1, interferon gamma-induced protein
      10, and monokine induced by interferon gamma and a concomitant decrease in the
      adipose-specific cytokine adiponectin. In conclusion, our study demonstrates for
      the first time that in male mice, GPER regulates metabolic parameters associated
      with obesity and diabetes. 

PMID- 23970786
TI  - ERbeta selective agonist inhibits angiotensin-induced cardiovascular pathology in
      female mice.
AB  - Cardiac hypertrophy in humans can progress to cardiac failure if the underlying
      impetus is poorly controlled. An important direct stimulator of hypertrophy and
      its progression is the angiotensin II (AngII) peptide. AngII also causes
      hypertension that indirectly contributes to cardiac hypertrophy. Others and we
      have shown that estrogens acting through the estrogen receptor (ER)-beta can
      inhibit AngII-induced or other forms of cardiac hypertrophy in mice. However, the
      proliferative effects of estrogen in breast and uterus that promote the
      development of malignancy preclude using the steroid to prevent cardiac disease
      progression. We therefore tested whether an ERbeta selective agonist, beta-LGND2,
      can prevent hypertension and cardiac pathology in female mice. AngII infusion
      over 3 weeks significantly stimulated systolic and diastolic hypertension,
      cardiac hypertrophy, and cardiac fibrosis, all significantly prevented by beta
      LGND2 in wild-type but not in ERbeta genetically deleted mice. AngII stimulated
      the Akt kinase to phosphorylate and inhibit the glycogen synthase kinase-3beta
      kinase, leading to GATA4 transcription factor activation and hypertrophic mRNA
      expression. As a novel mechanism, all these actions were opposed by estradiol and
      beta-LGND2. Our findings provide additional understanding of the antihypertrophic
      effects of ERbeta and serve as an impetus to test specific receptor agonists in
      humans to prevent the worsening of cardiovascular disease. 

PMID- 23970787
TI  - Expression profiling of intestinal tissues implicates tissue-specific genes and
      pathways essential for thyroid hormone-induced adult stem cell development.
AB  - The study of the epithelium during development in the vertebrate intestine
      touches upon many contemporary aspects of biology: to name a few, the formation
      of the adult stem cells (ASCs) essential for the life-long self-renewal and the
      balance of stem cell activity for renewal vs cancer development. Although
      extensive analyses have been carried out on the property and functions of the
      adult intestinal stem cells in mammals, little is known about their formation
      during development due to the difficulty of manipulating late-stage, uterus
      enclosed embryos. The gastrointestinal tract of the amphibian Xenopus laevis is
      an excellent model system for the study of mammalian ASC formation, cell
      proliferation, and differentiation. During T3-dependent amphibian metamorphosis,
      the digestive tract is extensively remodeled from the larval to the adult form
      for the adaptation of the amphibian from its aquatic herbivorous lifestyle to
      that of a terrestrial carnivorous frog. This involves de novo formation of ASCs
      that requires T3 signaling in both the larval epithelium and nonepithelial
      tissues. To understand the underlying molecular mechanisms, we have characterized
      the gene expression profiles in the epithelium and nonepithelial tissues by using
      cDNA microarrays. Our results revealed that T3 induces distinct tissue-specific
      gene regulation programs associated with the remodeling of the intestine,
      particularly the formation of the ASCs, and further suggested the existence of
      potentially many novel stem cell-associated genes, at least in the intestine
      during development. 

PMID- 23970789
TI  - Genetic variant RNF213 c.14576G>A in various phenotypes of intracranial major
      artery stenosis/occlusion.
AB  - BACKGROUND AND PURPOSE: Recently, we reported a common genetic variant, ring
      finger protein 213 (RNF213) c.14576G>A variant, a susceptibility gene for
      moyamoya disease (MMD), among patients with intracranial major artery
      stenosis/occlusion (ICASO) in a selected Japanese population. The aim of this 2
      center-based case-control study was to confirm our previous finding in a larger
      population. METHODS: Study participants were recruited from The University of
      Tokyo Hospital and Kanto Neurosurgical Hospital. The occurrence rate of
      c.14576G>A variant was investigated in 323 patients, 22 with definite MMD, 8 with
      unilateral MMD, 84 with ICASO in the absence of MMD (non-MMD ICASO), 34 with
      extracranial carotid atherosclerosis, 44 with cerebral aneurysm, 21 with
      intracerebral hemorrhage, and 110 control subjects. RESULTS: RNF213 c.14576G>A
      variant was found in 1.8% (2/110) of the normal control group and had significant
      associations with definite MMD (P<0.0001; odds ratio, 144.0; 95% confidence
      interval, 26.7-775.9), unilateral MMD (P=0.0001; odds ratio, 54.0; 95% confidence
      interval, 7.5-386.8), and non-MMD ICASO (P<0.0001; odds ratio, 16.8; 95%
      confidence interval, 3.81-74.5). There was no significant association with
      extracranial carotid atherosclerosis, cerebral aneurysm, or intracerebral
      hemorrhage. This result replicated our previous findings. CONCLUSIONS: A
      particular subset of patients with various phenotypes of ICASO has a common
      genetic variant, RNF213 c.14576G>A, indicating that RNF213 c.14576G>A variant is
      a high-risk allele for ICASO.

PMID- 23970788
TI  - TGF-beta superfamily member Nodal stimulates human beta-cell proliferation while
      maintaining cellular viability.
AB  - In an effort to expand human islets and enhance allogeneic islet transplant for
      the treatment of type 1 diabetes, identifying signaling pathways that stimulate
      human beta-cell proliferation is paramount. TGF-beta superfamily members, in
      particular activin-A, are likely involved in islet development and may contribute
      to beta-cell proliferation. Nodal, another TGF-beta member, is present in both
      embryonic and adult rodent islets. Nodal, along with its coreceptor, Cripto, are
      pro-proliferative factors in certain cell types. Although Nodal stimulates
      apoptosis of rat insulinoma cells (INS-1), Nodal and Cripto signaling have not
      been studied in the context of human islets. The current study investigated the
      effects of Nodal and Cripto on human beta-cell proliferation, differentiation,
      and viability. In the human pancreas and isolated human islets, we observed Nodal
      mRNA and protein expression, with protein expression observed in beta and alpha
      cells. Cripto expression was absent from human islets. Furthermore, in cultured
      human islets, exogenous Nodal stimulated modest beta-cell proliferation and
      inhibited alpha-cell proliferation with no effect on cellular viability,
      apoptosis, or differentiation. Nodal stimulated the phosphorylation of mothers
      against decapentaplegic (SMAD)-2, with no effect on AKT or MAPK signaling,
      suggesting phosphorylated SMAD signaling was involved in beta-cell proliferation.
      Cripto had no effect on human islet cell proliferation, differentiation, or
      viability. In conclusion, Nodal stimulates human beta-cell proliferation while
      maintaining cellular viability. Nodal signaling warrants further exploration to
      better understand and enhance human beta-cell proliferative capacity. 

PMID- 23970790
TI  - Suprascapular nerve block for shoulder pain in the first year after stroke: a
      randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: Shoulder pain is a common complication after stroke that
      can impede participation in rehabilitation and has been associated with poorer
      outcomes. Evidence-based treatments for hemiplegic shoulder pain are limited.
      Suprascapular nerve block (SSNB) is a safe and effective treatment of shoulder
      pain associated with arthritic shoulder conditions, but its usefulness in a
      stroke population is unclear. METHODS: We undertook a randomized controlled trial
      assessing the effectiveness of SSNB in a population of 64 stroke patients (onset
      < 1 year) with hemiplegic shoulder pain. The primary outcome was pain measured on
      a visual analogue scale (VAS). Secondary outcomes were disability (Modified
      Rankin Scale, Croft Disability Index) and quality of life (EuroQol Health
      Questionnaire). All participants were assessed before randomization, and at 1, 4,
      and 12 weeks postintervention. Both groups continued with routine therapy.
      RESULTS: Although both intervention and control groups demonstrated reduction in
      pain score, participants who received SSNB consistently demonstrated superior,
      statistically significant pain reduction compared with placebo. Mean VAS
      reduction in the SSNB group was >18 mm greater than participants receiving
      placebo injection. The number needed to treat with SSNB to reduce 1 stroke
      survivor's pain by 50% at 4 weeks is 4. No significant differences in function or
      quality of life were observed. No adverse events were reported. CONCLUSIONS:
      Suprascapular nerve block is a safe and effective treatment for patients with
      hemiplegic shoulder pain. CLINICAL TRIAL REGISTRATION URL:
      http://www.anzctr.org.au. Unique identifier: ACTRN12609000621213.

PMID- 23970791
TI  - Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly?
AB  - BACKGROUND AND PURPOSE: We previously reported increased benefit and reduced
      mortality after ultra-early stroke thrombolysis in a single center. We now
      explored in a large multicenter cohort whether extra benefit of treatment within
      90 minutes from symptom onset is uniform across predefined stroke severity
      subgroups, as compared with later thrombolysis. METHODS: Prospectively collected
      data of consecutive ischemic stroke patients who received i.v. thrombolysis in 10
      European stroke centers were merged. Logistic regression tested association
      between treatment delays, as well as excellent 3-month outcome (modified Rankin
      scale, 0-1), and mortality. The association was tested separately in tertiles of
      baseline National Institutes of Health Stroke Scale. RESULTS: In the whole cohort
      (n=6856), shorter onset-to-treatment time as a continuous variable was
      significantly associated with excellent outcome (P<0.001). Every fifth patient
      had onset-to-treatment time<=90 minutes, and these patients had lower frequency
      of intracranial hemorrhage. After adjusting for age, sex, admission glucose
      level, and year of treatment, onset-to-treatment time<=90 minutes was associated
      with excellent outcome in patients with National Institutes of Health Stroke
      Scale 7 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11-1.70; P=0.004),
      but not in patients with baseline National Institutes of Health Stroke Scale>12
      (odds ratio, 1.00; 95% confidence interval, 0.76-1.32; P=0.99) and baseline
      National Institutes of Health Stroke Scale 0 to 6 (odds ratio, 1.04; 95%
      confidence interval, 0.78-1.39; P=0.80). In the latter, however, an independent
      association (odds ratio, 1.51; 95% confidence interval, 1.14-2.01; P<0.01) was
      found when considering modified Rankin scale 0 as outcome (to overcome the
      possible ceiling effect from spontaneous better prognosis of patients with mild
      symptoms). Ultra-early treatment was not associated with mortality. CONCLUSIONS:
      I.v. thrombolysis within 90 minutes is, compared with later thrombolysis,
      strongly and independently associated with excellent outcome in patients with
      moderate and mild stroke severity.

PMID- 23970792
TI  - Smoking as a risk factor for stroke in women compared with men: a systematic
      review and meta-analysis of 81 cohorts, including 3,980,359 individuals and
      42,401 strokes.
AB  - BACKGROUND AND PURPOSE: It is currently unknown whether the excess risk of stroke
      by smoking is the same for women and men. We performed a systematic review and
      meta-analysis to estimate the effect of smoking on stroke in women compared with
      men. METHODS: PubMed MEDLINE was systematically searched for prospective
      population-based cohort studies published between January 1, 1966, and January
      26, 2013. Studies that presented sex-specific estimates of the relative risk of
      stroke comparing current smoking with nonsmoking and its associated variability
      were selected. The sex-specific relative risks and their ratio (RRR), comparing
      women with men, were pooled using random-effects meta-analysis with inverse
      variance weighting. Similarly, the RRR for former versus never smoking was
      pooled. RESULTS: Data from 81 prospective cohort studies that included 3,980,359
      individuals and 42,401 strokes were available. Smoking was an independent risk
      factor for stroke in both sexes. Overall, the pooled multiple-adjusted RRR
      indicated a similar risk of stroke associated with smoking in women compared with
      men (RRR, 1.06 [95% confidence interval, 0.99-1.13]). In a regional analysis,
      there was evidence of a more harmful effect of smoking in women than in men in
      Western (RRR, 1.10 [1.02-1.18)] but not in Asian (RRR, 0.97 [0.87-1.09])
      populations. Compared with never-smokers, the beneficial effects of quitting
      smoking among former smokers on stroke risk were similar between the sexes (RRR,
      1.10 [0.99-1.22]). CONCLUSIONS: Compared with nonsmokers, the excess risk of
      stroke is at least as great among women who smoke compared with men who smoke.

PMID- 23970793
TI  - Clinical significance of androgen receptor and its phosphorylated form in breast
      cancer.

PMID- 23970794
TI  - A novel approach to estimating the prevalence of untaxed cigarettes in the USA:
      findings from the 2009 and 2010 international tobacco control surveys.
AB  - BACKGROUND: Increases in tobacco taxes are effective in reducing tobacco
      consumption, but because of the addictive nature of cigarettes, smokers often
      seek out less expensive sources of cigarettes. The objective of this study is to
      estimate the prevalence of cigarette packs that are untaxed by the state in which
      the participant resides in a sample of US smokers at two time points. METHODS:
      Data for this study were taken from the 2009 and 2010 waves of the International
      Tobacco Control United States Survey. Members of this nationally representative
      cohort of smokers were invited to send us an unopened pack of their usual brand
      of cigarettes. RESULTS: In 2009, 318 packs were received from 401 eligible
      participants (79%). In 2010, 366 packs were received from 491 eligible
      participants (75%). In total, 20% of the packs in 2009 and 21% in 2010 were
      classified as untaxed by the participant's state of residence. The prevalence of
      untaxed cigarettes was higher in states with higher-excise taxes. Smokers who do
      not have a plan to quit were significantly more likely to have sent back a pack
      that was classified as untaxed by the participant's state of residence.
      CONCLUSIONS: One in five packs were untaxed with rates higher in states with
      higher-excise taxes. It is unclear whether these estimates differ from the actual
      prevalence of cigarettes that are untaxed by a smoker's state of residence.
      Harmonisation of excise tax rates across all 50 US states might be one method of
      reducing or eliminating the incentive to avoid or evade these taxes.

PMID- 23970795
TI  - Searching for a European policy for food and nutrition.

PMID- 23970796
TI  - De novo generation of infectious prions with bacterially expressed recombinant
      prion protein.
AB  - The prion hypothesis is strongly supported by the fact that prion infectivity and
      the pathogenic conformer of prion protein (PrP) are simultaneously propagated in
      vitro by the serial protein misfolding cyclic amplification (sPMCA). However, due
      to sPMCA's enormous amplification power, whether an infectious prion can be
      formed de novo with bacterially expressed recombinant PrP (rPrP) remains to be
      satisfactorily resolved. To address this question, we performed unseeded sPMCA
      with rPrP in a laboratory that has never been exposed to any native prions. Two
      types of proteinase K (PK)-resistant and self-perpetuating recombinant PrP
      conformers (rPrP-res) with PK-resistant cores of 17 or 14 kDa were generated. A
      bioassay revealed that rPrP-res(17kDa) was highly infectious, causing prion
      disease in wild-type mice with an average survival time of about 172 d. In
      contrast, rPrP-res(14kDa) completely failed to induce any disease. Our findings
      reveal that sPMCA is sufficient to initiate various self-perpetuating PK
      resistant rPrP conformers, but not all of them possess in vivo infectivity.
      Moreover, generating an infectious prion in a prion-free environment establishes
      that an infectious prion can be formed de novo with bacterially expressed rPrP.

PMID- 23970797
TI  - The noninflammatory role of high mobility group box 1/Toll-like receptor 2 axis
      in the self-renewal of mammary cancer stem cells.
AB  - Cancer stem cells (CSCs) are responsible for tumor progression, metastases,
      resistance to therapy, and tumor recurrence. Therefore, the identification of
      molecules involved in CSC self-renewal is a necessary step toward more effective
      therapies. To this aim, through the transcription profiling of the murine
      ErbB2(+) tumor cell line TUBO vs. derived CSC-enriched mammospheres, Toll-like
      receptor 2 (TLR2) was identified as 2-fold overexpressed in CSCs, as confirmed by
      qPCR and cytofluorimetric analysis. TLR2 signaling inhibition impaired in vitro
      mammosphere generation in murine TUBO (60%) and 4T1 (30%) and human MDA-MB-231
      (50%), HCC1806 (60%), and MCF7 (50%) cells. In CSC, TLR2 was activated by
      endogenous high-mobility-group box 1 (HMGB1), inducing IkappaBalpha
      phosphorylation, IL-6 and TGFbeta secretion, and, consequently, STAT3 and Smad3
      activation. In vivo TLR2 inhibition blocked TUBO tumor takes in 9/14 mice and
      induced a 2-fold reduction in lung metastases development by decreasing cell
      proliferation and vascularization and increasing apoptosis. Collectively, these
      results demonstrate that murine and human mammary CSCs express TLR2 and its
      ligand HMGB1; this autocrine loop plays a pivotal role in CSC self-renewal,
      tumorigenesis, and metastatic ability. These findings, while providing evidence
      against the controversial use of TLR2 agonists in antitumor therapy, lay out new
      paths toward the design of anticancer treatments.

PMID- 23970798
TI  - Simultaneous breakdown of multiple antibiotic resistance mechanisms in S. aureus.
AB  - In previous studies, the oligo-acyl-lysyl (OAK) C12(omega7)K-beta12 added to
      cultures of gram-positive bacteria exerted a bacteriostatic activity that was
      associated with membrane depolarization, even at high concentrations. Here, we
      report that multidrug-resistant Staphylococcus aureus strains, unlike other gram
      positive species, have reverted to the sensitive phenotype when exposed to
      subminimal inhibitory concentrations (sub-MICs) of the OAK, thereby increasing
      antibiotics potency by up to 3 orders of magnitude. Such chemosensitization was
      achieved using either cytoplasm or cell-wall targeting antibiotics. Moreover,
      eventual emergence of resistance to antibiotics was significantly delayed. Using
      the mouse peritonitis-sepsis model, we show that on single-dose administration of
      oxacillin and OAK combinations, death induced by a lethal staphylococcal
      infection was prevented in a synergistic manner, thereby supporting the
      likelihood for synergism to persist under in vivo conditions. Toward illuminating
      the molecular basis for these observations, we present data arguing that sub-MIC
      OAK interactions with the plasma membrane can inhibit proton-dependent signal
      transduction responsible for expression and export of resistance factors, as
      demonstrated for beta-lactamase and PBP2a. Collectively, the data reveal a
      potentially useful approach for overcoming antibiotic resistance and for
      preventing resistance from emerging as readily as when bacteria are exposed to an
      antibiotic alone.

PMID- 23970799
TI  - Learning the right lessons from the SUPPORT study controversy.

PMID- 23970801
TI  - Microcystin-LR exhibits immunomodulatory role in mouse primary hepatocytes
      through activation of the NF-kappaB and MAPK signaling pathways.
AB  - Microcystin-leucine-arginine (MCLR) is an environmental toxin from harmful algae,
      which has been linked to hepatotoxicity with high risks associated with liver
      disease. In this study, we explored the role of MCLR in NF-kappaB and mitogen
      activated protein kinase (MAPK) signaling pathways, which are important in
      regulating inflammatory and immune responses, in human hepatoma cell line HepG2
      and primary mouse hepatocytes (PMHs). By in vitro cell-free and luciferase
      reporter systems, Western blotting with antiphospho-inhibitory protein of NF
      kappaB (IkappaBalpha)/c-Jun N-terminal kinase (JNK)/extracellular signal
      regulated kinase 1/2 (ERK1/2) antibody, it was found that at noncytotoxic
      concentrations (<= 20 nM MCLR in PMHs, 1-1000 nM in HepG2), MCLR treatment alone
      promoted activation of NF-kappaB and MAPK pathways and modulated TNF-alpha
      induced activation of the 2 pathways in both cell models. By ELISA assay, MCLR
      was found to induce production of proinflammatory cytokine IL-6 in PMHs. At
      cytotoxic concentrations (>= 50 nM MCLR in PMHs), MCLR dramatically reduced cell
      viability and damaged cell morphology in PMHs, as determined by the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and transmission
      electron microscopy analysis. These results suggest that MCLR below 20 nM has
      significant immunomodulatory activities through activation of NF-kappaB and MAPK
      signaling pathways, and PMHs are more sensitive to MCLR-induced cytotoxicity than
      HepG2. To our knowledge, this is the first report showing the immunomodulatory
      role of MCLR in hepatocytes. Our results provide a better understanding of the
      molecular mechanisms underlying MCLR-induced hepatotoxicity.

PMID- 23970800
TI  - Pretreatment with TCDD exacerbates liver injury from Concanavalin A: critical
      role for NK cells.
AB  - For many liver diseases, including viral and autoimmune hepatitis, immune cells
      play an important role in the development and progression of liver injury.
      Concanavalin A (Con A) administration to rodents has been used as a model of
      immune-mediated liver injury resembling human autoimmune hepatitis. 2,3,7,8
      Tetrachlorodibenzo-p-dioxin (TCDD) has been demonstrated to alter the development
      of immune-mediated diseases. Mice pretreated with TCDD developed exacerbated
      liver injury in response to administration of a mild dose (6 mg/kg) of Con A. In
      the present study, we tested the hypothesis that TCDD pretreatment exacerbates
      Con A-induced liver injury by enhancing the activation and recruitment of
      accessory cell types including neutrophils, macrophages, and natural killer (NK)
      cells. Mice were treated with 0, 0.3, 3, or 30 MUg/kg TCDD and 4 days later with
      Con A or saline. TCDD pretreatment with doses of 3 and 30 MUg/kg significantly
      increased liver injury from Con A administration. The plasma concentrations of
      neutrophil chemokines were significantly increased in TCDD-pretreated mice after
      Con A administration. NKT cell-deficient (CD1d KO) mice were used to examine
      whether NKT cells were required for TCDD/Con A-induced liver injury. CD1d KO mice
      were completely protected from liver injury induced by treatment with Con A
      alone, whereas the injury from TCDD/Con A treatment was reduced but not
      eliminated. However, T-cell deficient (RAG1 KO) mice were protected from liver
      injury induced by Con A irrespective of pretreatment with TCDD. TCDD/Con A
      treatment increased the percentage of NK cells expressing the activation marker
      CD69. Depletion of NK cells prior to treatment resulted in significant reductions
      in plasma interferon-gamma and liver injury from TCDD/Con A treatment. In
      summary, exposure to TCDD exacerbated the immune-mediated liver injury induced by
      Con A, and our findings suggest that NK cells play a critical role in this
      response.

PMID- 23970804
TI  - Orlov spectra as a filtered cohomology theory.
AB  - This paper presents a new approach to the dimension theory of triangulated
      categories by considering invariants that arise in the pretriangulated setting.

PMID- 23970805
TI  - INTERGENERATIONAL OCCUPATIONAL MOBILITY IN BRITAIN AND THE U.S. SINCE 1850:
      COMMENT.
AB  - Using historical census and survey data, Long and Ferrie (forthcoming) found a
      significant decline in social mobility in the United States from 1880 to 1973. We
      present two critiques of the Long-Ferrie study. First, the data quality of the
      Long-Ferrie study is more limiting than the authors acknowledge. Second, and more
      critically, they applied a method ill-suited for measuring social mobility of
      farmers in a comparative study between 1880 and 1973, a period in which the
      proportion of farmers dramatically declined in the U.S. We show that Long and
      Ferrie's main conclusion is all driven by this misleading result for farmers.

PMID- 23970802
TI  - SLCO1B1 variants and urine arsenic metabolites in the Strong Heart Family Study.
AB  - Arsenic species patterns in urine are associated with risk for cancer and
      cardiovascular diseases. The organic anion transporter coded by the gene SLCO1B1
      may transport arsenic species, but its association with arsenic metabolites in
      human urine has not yet been studied. The objective of this study is to evaluate
      associations of urine arsenic metabolites with variants in the candidate gene
      SLCO1B1 in adults from the Strong Heart Family Study. We estimated associations
      between % arsenic species biomarker traits and 5 single-nucleotide polymorphisms
      (SNPs) in the SLCO1B1 gene in 157 participants, assuming additive genetics.
      Linear regression models for each SNP accounted for kinships and were adjusted
      for sex, body mass index, and study center. The minor allele of rs1564370 was
      associated with lower %MMA (p = .0003) and higher %DMA (p = .0002), accounting
      for 8% of the variance for %MMA and 9% for %DMA. The rs1564370 minor allele
      homozygote frequency was 17% and the heterozygote frequency was 43%. The minor
      allele of rs2291075 was associated with lower %MMA (p = .0006) and higher %DMA (p
      = .0014), accounting for 7% of the variance for %MMA and 5% for %DMA. The
      frequency of rs2291075 minor allele homozygotes was 1% and of heterozygotes was
      15%. Common variants in SLCO1B1 were associated with differences in arsenic
      metabolites in a preliminary candidate gene study. Replication of this finding in
      other populations and analyses with respect to disease outcomes are needed to
      determine whether this novel candidate gene is important for arsenic-associated
      disease risks. 

PMID- 23970803
TI  - Concordance of transcriptional and apical benchmark dose levels for conazole
      induced liver effects in mice.
AB  - The ability to anchor chemical class-based gene expression changes to phenotypic
      lesions and to describe these changes as a function of dose and time informs mode
      of-action determinations and improves quantitative risk assessments. Previous
      global expression profiling identified a 330-probe cluster differentially
      expressed and commonly responsive to 3 hepatotumorigenic conazoles
      (cyproconazole, epoxiconazole, and propiconazole) at 30 days. Extended to 2 more
      conazoles (triadimefon and myclobutanil), the present assessment encompasses 4
      tumorigenic and 1 nontumorigenic conazole. Transcriptional benchmark dose levels
      (BMDL(T)) were estimated for a subset of the cluster with dose-responsive
      behavior and a >= 5-fold increase or decrease in signal intensity at the highest
      dose. These genes primarily encompassed CAR/RXR activation, P450 metabolism,
      liver hypertrophy- glutathione depletion, LPS/IL-1-mediated inhibition of RXR,
      and NRF2-mediated oxidative stress pathways. Median BMDL(T) estimates from the
      subset were concordant (within a factor of 2.4) with apical benchmark doses
      (BMDL(A)) for increased liver weight at 30 days for the 5 conazoles. The 30-day
      median BMDL(T) estimates were within one-half order of magnitude of the chronic
      BMDLA for hepatocellular tumors. Potency differences seen in the dose-responsive
      transcription of certain phase II metabolism, bile acid detoxification, and lipid
      oxidation genes mirrored each conazole's tumorigenic potency. The 30-day BMDL(T)
      corresponded to tumorigenic potency on a milligram per kilogram day basis with
      cyproconazole > epoxiconazole > propiconazole > triadimefon > myclobutanil
      (nontumorigenic). These results support the utility of measuring short-term gene
      expression changes to inform quantitative risk assessments from long-term
      exposures.

PMID- 23970806
TI  - Asynchronous collision integrators: Explicit treatment of unilateral contact with
      friction and nodal restraints.
AB  - This article presents asynchronous collision integrators and a simple
      asynchronous method treating nodal restraints. Asynchronous discretizations allow
      individual time step sizes for each spatial region, improving the efficiency of
      explicit time stepping for finite element meshes with heterogeneous element
      sizes. The article first introduces asynchronous variational integration being
      expressed by drift and kick operators. Linear nodal restraint conditions are
      solved by a simple projection of the forces that is shown to be equivalent to
      RATTLE. Unilateral contact is solved by an asynchronous variant of decomposition
      contact response. Therein, velocities are modified avoiding penetrations.
      Although decomposition contact response is solving a large system of linear
      equations (being critical for the numerical efficiency of explicit time stepping
      schemes) and is needing special treatment regarding overconstraint and linear
      dependency of the contact constraints (for example from double-sided node-to
      surface contact or self-contact), the asynchronous strategy handles these
      situations efficiently and robust. Only a single constraint involving a very
      small number of degrees of freedom is considered at once leading to a very
      efficient solution. The treatment of friction is exemplified for the Coulomb
      model. Special care needs the contact of nodes that are subject to restraints.
      Together with the aforementioned projection for restraints, a novel efficient
      solution scheme can be presented. The collision integrator does not influence the
      critical time step. Hence, the time step can be chosen independently from the
      underlying time-stepping scheme. The time step may be fixed or time-adaptive. New
      demands on global collision detection are discussed exemplified by position codes
      and node-to-segment integration. Numerical examples illustrate convergence and
      efficiency of the new contact algorithm. Copyright (c) 2013 The Authors.
      International Journal for Numerical Methods in Engineering published by John
      Wiley & Sons, Ltd.

PMID- 23970807
TI  - SELF-STIGMA AND COMING OUT ABOUT ONE'S MENTAL ILLNESS.
AB  - Self-stigma can undermine self-esteem and self-efficacy of people with serious
      mental illness. Coming out may be one way of handling self-stigma and it was
      expected that coming out would mediate the effects of self-stigma on quality of
      life. This study compares coming out to other approaches of controlling self
      stigma. Eighty-five people with serious mental illness completed measures of
      coming out (called the Coming Out with Mental Illness Scale, COMIS), self-stigma,
      quality of life, and strategies for managing self-stigma. An exploratory factor
      analysis of the COMIS uncovered two constructs: benefits of being out (BBO) and
      reasons for staying in. A mediational analysis showed BBO diminished self-stigma
      effects on quality of life. A factor analysis of measures of managing self-stigma
      yielded three factors. Benefits of being out was associated with two of these:
      affirming strategies and becoming aloof, not with strategies of shame.
      Implications for how coming out enhances the person's quality of life are
      discussed.

PMID- 23970808
TI  - More on how and why: a response to commentaries.
AB  - We are grateful to the commentators for taking the time to respond to our
      article. Too many interesting and important points have been raised for us to
      tackle them all in this response, and so in the below we have sought to draw out
      the major themes. These include problems with both the term 'ultimate causation'
      and the proximate-ultimate causation dichotomy more generally, clarification of
      the meaning of reciprocal causation, discussion of issues related to the nature
      of development and phenotypic plasticity and their roles in evolution, and
      consideration of the need for an extended evolutionary synthesis.

PMID- 23970809
TI  - Coevolutionary aesthetics in human and biotic artworlds.
AB  - This work proposes a coevolutionary theory of aesthetics that encompasses both
      biotic and human arts. Anthropocentric perspectives in aesthetics prevent the
      recognition of the ontological complexity of the aesthetics of nature, and the
      aesthetic agency of many non-human organisms. The process of evaluative
      coevolution is shared by all biotic advertisements. I propose that art consists
      of a form of communication that coevolves with its own evaluation. Art and art
      history are population phenomena. I expand Arthur Danto's Artworld concept to any
      aesthetic population of producers and evaluators. Current concepts of art cannot
      exclusively circumscribe the human arts from many forms of non-human biotic art.
      Without assuming an arbitrarily anthropocentric perspective, any concept of art
      will need to engage with biodiversity, and either recognize many instances of
      biotic advertisements as art, or exclude some instances of human art.
      Coevolutionary aesthetic theory provides a heuristic account of aesthetic change
      in both human and biotic artworlds, including the coevolutionary origin of
      aesthetic properties and aesthetic value within artworlds. Restructuring
      aesthetics, art criticism, and art history without human beings at the organizing
      centers of these disciplines stimulate new progress in our understanding of art,
      and the unique human contributions to aesthetics and aesthetic diversity.

PMID- 23970810
TI  - The Relationship between Pubertal Timing and Delinquent Behavior in Maltreated
      Male and Female Adolescents.
AB  - This study examined the relationship between pubertal timing and delinquent
      behavior across two time points in a sample of 303 maltreated and 151 comparison
      adolescents aged 9-13 years at enrollment. The first aim was to examine the
      relationship between pubertal timing and delinquency for the total sample and
      then to test for gender differences using multiple-group models. The second aim
      was to examine the interaction effect of pubertal timing and maltreatment on
      delinquency as well as gender differences for this interaction effect. Results
      showed that earlier pubertal timing was related to higher delinquency and this
      relationship was not significantly different for males and females. Maltreatment
      did not moderate the relationship between pubertal timing and delinquency for the
      total sample; however, there was evidence of a three-way interaction. These
      findings highlight the need to examine contextual factors that may affect the
      amplification and direction of these relationships.

PMID- 23970811
TI  - Determining a Surrogate Contact Pair in a Hertzian Contact Problem.
AB  - Laboratory testing of contact phenomena can be prohibitively expensive if the
      interacting bodies are geometrically complicated. This work demonstrates means to
      mitigate such problems by exploiting the established observation that two
      geometrically dissimilar contact pairs may exhibit the same contact mechanics.
      Specific formulas are derived that allow a complicated Hertzian contact pair to
      be replaced with an inexpensively manufactured and more easily fixtured surrogate
      pair, consisting of a plane and a spheroid, which has the same (to second-order
      accuracy) contact area and pressure distribution as the original complicated
      geometry. This observation is elucidated by using direct tensor notation to
      review a key assertion in Hertzian theory; namely, geometrically complicated
      contacting surfaces can be described to second-order accuracy as contacting
      ellipsoids. The surrogate spheroid geometry is found via spectral decomposition
      of the original pair's combined Hessian tensor. Some numerical examples using
      free-form surfaces illustrate the theory, and a laboratory test validates the
      theory under a common scenario of normally compressed convex surfaces. This
      theory for a Hertzian contact substitution may be useful in simplifying the
      contact, wear, or impact testing of complicated components or of their
      constituent materials.

PMID- 23970812
TI  - Sildenafil (Viagra) protective effects on neuroinflammation: the role of iNOS/NO
      system in an inflammatory demyelination model.
AB  - We recently demonstrated that sildenafil reduces the expression of cytokines, COX
      2, and GFAP in a demyelinating model induced in wild-type (WT) mice. Herein, the
      understandings of the neuroprotective effect of sildenafil and the mediation of
      iNOS/NO system on inflammatory demyelination induced by cuprizone were
      investigated. The cerebella of iNOS(-/-) mice were examined after four weeks of
      treatment with cuprizone alone or combined with sildenafil. Cuprizone increased
      GFAP, Iba-1, TNF- alpha , COX-2, IL-1 beta , and IFN- gamma expression, decreased
      expression of glutathione S-transferase pi (GSTpi), and damaged myelin in iNOS(-/
      ) mice. Sildenafil reduced Iba-1, IFN- gamma , and IL-1 beta levels but had no
      effect on the expression of GFAP, TNF- alpha , and COX-2 compared to the
      cuprizone group. Sildenafil elevated GSTpi levels and improved the myelin
      structure/ultrastructure. iNOS(-/-) mice suffered from severe inflammation
      following treatment with cuprizone, while WT mice had milder inflammation, as
      found in the previous study. It is possible that inflammatory regulation through
      iNOS-feedback is absent in iNOS(-/-) mice, making them more susceptible to
      inflammation. Sildenafil has at least a partial anti-inflammatory effect through
      iNOS inhibition, as its effect on iNOS(-/-) mice was limited. Further studies are
      required to explain the underlying mechanism of the sildenafil effects. 

PMID- 23970813
TI  - Persistent inflammation in the CNS during chronic EAE despite local absence of IL
      17 production.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an artificially induced
      demyelination of the central nervous system (CNS) that resembles multiple
      sclerosis in its clinical, histopathological, and immunological features.
      Activated Th1 and Th17 cells are thought to be the main immunological players
      during EAE development. This study was designed to evaluate peripheral and local
      contribution of IL-17 to acute and chronic EAE stages. C57BL/6 mice were
      immunized with MOG plus complete Freund's adjuvant followed by pertussis toxin.
      Mice presented an initial acute phase characterized by accentuated weight loss
      and high clinical score, followed by a partial recovery when the animals reached
      normal body weight and smaller clinical scores. Spleen cells stimulated with MOG
      produced significantly higher levels of IFN- gamma during the acute period
      whereas similar IL-17 levels were produced during both disease stages. CNS
      infiltrating cells stimulated with MOG produced similar amounts of IFN- gamma
      but, IL-17 was produced only at the acute phase of EAE. The percentage of Foxp3+
      Treg cells, at the spleen and CNS, was elevated during both phases. The degree of
      inflammation was similar at both disease stages. Partial clinical recovery
      observed during chronic EAE was associated with no IL-17 production and presence
      of Foxp3+ Treg cells in the CNS. 

PMID- 23970814
TI  - Dysregulated circulating dendritic cell function in ulcerative colitis is
      partially restored by probiotic strain Lactobacillus casei Shirota.
AB  - BACKGROUND: Dendritic cells regulate immune responses to microbial products and
      play a key role in ulcerative colitis (UC) pathology. We determined the
      immunomodulatory effects of probiotic strain Lactobacillus casei Shirota (LcS) on
      human DC from healthy controls and active UC patients. METHODS: Human blood DC
      from healthy controls (control-DC) and UC patients (UC-DC) were conditioned with
      heat-killed LcS and used to stimulate allogeneic T cells in a 5-day mixed
      leucocyte reaction. RESULTS: UC-DC displayed a reduced stimulatory capacity for T
      cells (P < 0.05) and enhanced expression of skin-homing markers CLA and CCR4 on
      stimulated T cells (P < 0.05) that were negative for gut-homing marker beta7. LcS
      treatment restored the stimulatory capacity of UC-DC, reflecting that of control
      DC. LcS treatment conditioned control-DC to induce CLA on T cells in conjunction
      with beta7, generating a multihoming profile, but had no effects on UC-DC.
      Finally, LcS treatment enhanced DC ability to induce TGFbeta production by T
      cells in controls but not UC patients. CONCLUSIONS: We demonstrate a systemic,
      dysregulated DC function in UC that may account for the propensity of UC patients
      to develop cutaneous manifestations. LcS has multifunctional immunoregulatory
      activities depending on the inflammatory state; therapeutic effects reported in
      UC may be due to promotion of homeostasis.

PMID- 23970815
TI  - Extracellular signal-regulated kinase is a direct target of the anti-inflammatory
      compound amentoflavone derived from Torreya nucifera.
AB  - Amentoflavone is a biflavonoid compound with antioxidant, anticancer,
      antibacterial, antiviral, anti-inflammatory, and UV-blocking activities that can
      be isolated from Torreya nucifera, Biophytum sensitivum, and Selaginella
      tamariscina. In this study, the molecular mechanism underlying amentoflavone's
      anti-inflammatory activity was investigated. Amentoflavone dose dependently
      suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in
      RAW264.7 cells stimulated with the TLR4 ligand lipopolysaccharide (LPS; derived
      from Gram-negative bacteria). Amentoflavone suppressed the nuclear translocation
      of c-Fos, a subunit of activator protein (AP)-1, at 60 min after LPS stimulation
      and inhibited the activity of purified and immunoprecipitated extracellular
      signal-regulated kinase (ERK), which mediates c-Fos translocation. In agreement
      with these results, amentoflavone also suppressed the formation of a molecular
      complex including ERK and c-Fos. Therefore, our data strongly suggest that
      amentoflavone's immunopharmacological activities are due to its direct effect on
      ERK. 

PMID- 23970816
TI  - Thrombospondin and VEGF-R: is there a correlation in inflammatory bowel disease?
AB  - Up to date several authors discussed interactions between cells forming
      inflammatory infiltrates in the course of inflammatory bowel disease (IBD),
      mainly dealing with endoscopic biopsy specimens. These usually contain only
      mucosa. We have evaluated full bowel wall sections, which seems to be especially
      important in patients with Crohn's disease (CD). The purpose of our study was to
      evaluate the relationship between vascular density and expression of
      thrombospondin-1 (TSP-1) and vascular endothelial growth factor receptor 1 (VEGFR
      1) in full-thickness tissue fragments of intestinal wall taken from patients
      after colectomy, comparing those with IBD to non-IBD control group. Histological
      sections were immunostained with antibodies against CD-31, TSP-1, and VEGFR-1 and
      analyzed by pathologists with the use of computer-assisted morphometrics. Our
      research showed significantly higher vascular density and vascular area
      percentage in all layers of bowel wall in patients with CD when compared to
      control. We have also demonstrated differences in vascular density distribution
      between ulcerative colitis (CU) and CD and between CU and control. However we
      have not found statistically significant correlation between those findings and
      VEGFR-1 or TSP-1 expression. Our results might suggest existence of different,
      TSP-1 independent pathways of antiangiogenesis in IBD. 

PMID- 23970818
TI  - IL-17 expression in dermatitis herpetiformis and bullous pemphigoid.
AB  - Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases
      associated with eosinophilic and neutrophilic infiltrations. Although cytokines
      are critical for the inflammatory process, there are single findings concerning
      concentration of IL-17 in bullous diseases. The goal of this study was to assess
      IL-17 expression in DH and BP patients. Skin biopsies were taken from 10 DH, 14
      BP patients and from 10 healthy subjects. The localization and expression of IL
      17 was studied by immunohistochemistry and the serum concentration was measured
      by immunoassays. Expression of IL-17 in the epidermis and in influxed cells in
      dermis was detected in skin biopsies. Expression of IL-17 was statistically
      higher in epidermis and infiltration cells in specimens from BP than from DH
      patients. Examined interleukin expression was detected in perilesional skin of
      all patients but it was much lower than in lesional skin. The expression of IL-17
      was not observed in biopsies from healthy people. Serum level of IL-17 was
      statistically higher in BP and DH groups as compared to control group. Our
      results provide the evidence that IL-17 may play an essential role in activating
      and recruiting eosinophils and neutrophils, which ultimately contribute to the
      tissue damage in DH and BP. 

PMID- 23970819
TI  - Advances in Applying Treatment Integrity Research for Dissemination and
      Implementation Science: Introduction to Special Issue.
AB  - This special series focuses upon the ways in which research on treatment
      integrity, a multidimensional construct including assessment of the content and
      quality of a psychosocial treatment delivered to a client as well as relational
      elements, can inform dissemination and implementation science. The five articles
      for this special series illustrate how treatment integrity concepts and methods
      can be applied across different levels of the mental health service system to
      advance dissemination and implementation science. In this introductory article,
      we provide an overview of treatment integrity research and describe three broad
      conceptual models that are relevant to the articles in the series. We conclude
      with a brief description of each of the five articles in the series.

PMID- 23970820
TI  - A Multilevel Analysis of Gender Differences in Psychological Distress Over Time.
AB  - Females have higher rates of depression than males, a disparity that emerges in
      adolescence and persists into adulthood. This study uses hierarchical linear
      modeling to assess the effects of school context on gender differences in
      depressive symptoms among adolescents based on two waves of data from the
      National Longitudinal Study of Adolescent Health (N = 9,709 teens, 127 schools).
      Analysis indicates significant school-level variation in both overall symptom
      levels and the average gender gap in depression net of prior symptoms and
      individual-level covariates. Aggregate levels of depressive symptomatology were
      positively associated with contextual-level socioeconomic status (SES)
      disadvantage. A cross-level contingency emerged for the relationship between
      gender and depressive symptoms with school SES and aggregate perceived community
      safety such that the gender "gap" was most apparent in contexts characterized by
      low SES disadvantage and high levels of perceived safety. These results highlight
      the importance of context to understanding the development of mental health
      disparities.

PMID- 23970817
TI  - Biological treatments: new weapons in the management of monogenic
      autoinflammatory disorders.
AB  - Treatment of monogenic autoinflammatory disorders, an expanding group of
      hereditary diseases characterized by apparently unprovoked recurrent episodes of
      inflammation, without high-titre autoantibodies or antigen-specific T cells, has
      been revolutionized by the discovery that several of these conditions are caused
      by mutations in proteins involved in the mechanisms of innate immune response,
      including components of the inflammasome, cytokine receptors, receptor
      antagonists, and oversecretion of a network of proinflammatory molecules. Aim of
      this review is to synthesize the current experience and the most recent evidences
      about the therapeutic approach with biologic drugs in pediatric and adult
      patients with monogenic autoinflammatory disorders. 

PMID- 23970821
TI  - Amniocentesis in HIV pregnant women: 16 years of experience.
AB  - The iatrogenic risk of HIV vertical transmission, calculated in initial
      epidemiologic studies, seemed to counterindicate invasive prenatal diagnosis
      (PND) procedures. The implementation of highly active antiretroviral therapy
      (HAART) represented a turning point in PND management, owing to a rapid and
      effective reduction of maternal viral load (VL). In the present study, we
      identified cases of vertical transmission in HIV-infected pregnant women who did
      amniocentesis in the second trimester of pregnancy (n = 27), from 1996 to 2011.
      We divided our sample into Group A--women under HAART when submitted to
      amniocentesis (n = 20) and Group B--women without antiretroviral therapy before
      amniocentesis (n = 7). We had 1 case of vertical transmission in Group B.
      Preconceptional or early first trimester HIV serology is essential to avoid
      performing an amniocentesis without antiretroviral therapy or viral suppression.
      When there is an indication for amniocentesis in an HIV-infected pregnant woman,
      it should be done if the patient is on HAART and, if possible, when VL is
      undetectable. Nowadays, with combined first trimester screening test to select
      pregnancies with high risk of aneuploidies, advanced maternal age is a less
      frequent indication to perform PND invasive procedures, representing an
      outstanding gain in prenatal diagnosis of this population.

PMID- 23970823
TI  - Doubly robust and efficient estimators for heteroscedastic partially linear
      single-index models allowing high dimensional covariates.
AB  - We study the heteroscedastic partially linear single-index model with an
      unspecified error variance function, which allows for high dimensional covariates
      in both the linear and the single-index components of the mean function. We
      propose a class of consistent estimators of the parameters by using a proper
      weighting strategy. An interesting finding is that the linearity condition which
      is widely assumed in the dimension reduction literature is not necessary for
      methodological or theoretical development: it contributes only to the
      simplification of non-optimal consistent estimation. We also find that the
      performance of the usual weighted least square type of estimators deteriorates
      when the non-parametric component is badly estimated. However, estimators in our
      family automatically provide protection against such deterioration, in that the
      consistency can be achieved even if the baseline non-parametric function is
      completely misspecified. We further show that the most efficient estimator is a
      member of this family and can be easily obtained by using non-parametric
      estimation. Properties of the estimators proposed are presented through
      theoretical illustration and numerical simulations. An example on gender
      discrimination is used to demonstrate and to compare the practical performance of
      the estimators.

PMID- 23970824
TI  - CAUSAL INFERENCE AND HETEROGENEITY BIAS IN SOCIAL SCIENCE.
AB  - Because of population heterogeneity, causal inference with observational data in
      social science may suffer from two possible sources of bias: (1) bias in
      unobserved pretreatment factors affecting the outcome even without treatment; and
      (2)bias due to heterogeneity in treatment effects. Even when we control for
      observed covariates, these two biases may occur if the classic ignorability
      assumption is untrue. In cases where the ignorability assumption is true,
      "composition bias" can occur if treatment propensity is systematically associated
      with heterogeneous treatment effects.

PMID- 23970822
TI  - Ovarian Damage During chemotherapy in Autoimmune Diseases: Broad Health
      Implications beyond Fertility.
AB  - Women with autoimmune diseases such as lupus, scleroderma, and vasculitis
      receiving cyclophosphamide for severe disease manifestations risk primary ovarian
      insufficiency(POI) due to gonadotoxicity of this therapy. In addition to loss of
      reproductive potential, POI is associated with increased risk of morbidity and
      mortality. Practitioners caring for women requiring gonadotoxic therapies should
      be familiar with long-term health implications of POI and strategies for ovarian
      preservation. Accumulating evidence supports the effectiveness of adjunctive
      gonadotropin releasing hormone analog (GnRH-a) for ovarian protection during
      gonadotoxic therapy in cancer and autoimmune populations. GnRH-a is less costly
      and invasive than assisted reproductive technologies used for achievement of
      future pregnancies, but is not Food and Drug Administration approved for ovarian
      preservation. This review focuses on POI comorbidities and strategies for
      mitigation of related sequelae, which can accumulate over decades of
      hypoesteogenism. These issues are arguably more pronounced for women with chronic
      autoimmune diseases, in whom superimposed POI further heightens risks of
      cardiovascular disease and osteoporosis. Therefore, even if future pregnancy is
      not desired, ovarian protection during gonadotoxic therapy should be a major goal
      of disease management.

PMID- 23970825
TI  - The Decline of Son Preference and Rise of Gender Indifference in Taiwan Since
      1990.
AB  - This study explores the change of married women's sex preference for children in
      Taiwan since 1990, finding that there was a substantial decline of son preference
      and rise of "gender indifference", defined as feeling indifferent about
      children's sex (as opposed to desiring an equal number of boys and girls, in
      which the sex of children is still a primary consideration). Results show that at
      the individual level female education was the strongest predictor for the
      preference; education was negatively associated with son preference and
      positively with gender indifference. Cohort difference was noticeable, too.
      Younger cohorts were better educated than older ones so that they were more
      neutral about the sex and less adherent to the traditional male preference;
      besides, from 1992 to 2002 there was a universal intra-cohort movement toward
      gender neutrality and away from son preference. When the younger cohorts
      gradually replaced the older ones as the main child bearers in the Taiwanese
      society, at the aggregate level son preference declined and gender indifference
      rose.

PMID- 23970826
TI  - Examining the predictive value of fertility preferences among Ghanaian women.
AB  - Despite extensive research, doubts remain regarding the degree of correspondence
      between prior stated fertility preferences and subsequent fertility behavior.
      Preference instability is a factor that potentially undermines predictiveness.
      Furthermore, if other predictors of fertility substantially explain fertility,
      then knowledge of preferences may contribute little to explaining or predicting
      individual fertility behavior. In this study, we examined these aspects of the
      study of individual fertility preference-behavior consistency. Using a
      prospective multi-wave panel dataset, we modeled the monthly likelihood of
      conception, taking into account the dynamic nature of preferences, and
      controlling for changing reproductive life cycle factors and stable socioeconomic
      background predictors of fertility. We demonstrate from a sample of fecund
      married Ghanaian women that fertility preferences retain independent predictive
      power in the model predicting the likelihood of conception.

PMID- 23970827
TI  - Characteristics and scenarios projection of climate change on the Tibetan
      Plateau.
AB  - The Fourth Assessment Report of the Intergovernmental Panel on Climate Change
      (IPCC AR4) presents twenty-two global climate models (GCMs). In this paper, we
      evaluate the ability of 22 GCMs to reproduce temperature and precipitation over
      the Tibetan Plateau by comparing with ground observations for 1961~1900. The
      results suggest that all the GCMs underestimate surface air temperature and most
      models overestimate precipitation in most regions on the Tibetan Plateau. Only a
      few models (each 5 models for precipitation and temperature) appear roughly
      consistent with the observations in annual temperature and precipitation
      variations. Comparatively, GFCM21 and CGMR are able to better reproduce the
      observed annual temperature and precipitation variability over the Tibetan
      Plateau. Although the scenarios predicted by the GCMs vary greatly, all the
      models predict consistently increasing trends in temperature and precipitation in
      most regions in the Tibetan Plateau in the next 90 years. The results suggest
      that the temperature and precipitation will both increase in all three periods
      under different scenarios, with scenario A1 increasing the most and scenario A1B
      increasing the least. 

PMID- 23970828
TI  - Performance prediction of a synchronization link for distributed aerospace
      wireless systems.
AB  - For reasons of stealth and other operational advantages, distributed aerospace
      wireless systems have received much attention in recent years. In a distributed
      aerospace wireless system, since the transmitter and receiver placed on separated
      platforms which use independent master oscillators, there is no cancellation of
      low-frequency phase noise as in the monostatic cases. Thus, high accurate time
      and frequency synchronization techniques are required for distributed wireless
      systems. The use of a dedicated synchronization link to quantify and compensate
      oscillator frequency instability is investigated in this paper. With the
      mathematical statistical models of phase noise, closed-form analytic expressions
      for the synchronization link performance are derived. The possible error
      contributions including oscillator, phase-locked loop, and receiver noise are
      quantified. The link synchronization performance is predicted by utilizing the
      knowledge of the statistical models, system error contributions, and sampling
      considerations. Simulation results show that effective synchronization error
      compensation can be achieved by using this dedicated synchronization link. 

PMID- 23970829
TI  - Do not hallow until you are out of the wood! Ultrasonographic detection of CPP
      crystal deposits in menisci: facts and pitfalls.
AB  - PURPOSE: Ultrasonography (US) has been demonstrated to be an important tool in
      the diagnosis of calcium pyrophosphate (CPP) crystal deposition disease. The aim
      of our study was to individuate and describe possible pitfalls in US detection of
      such deposits in menisci. PATIENTS AND METHODS: We enrolled all patients waiting
      to undergo knee replacement surgery due to osteoarthritis, for one-month period.
      Each patient underwent US examination of the knee, focusing on the menisci. After
      surgery, the menisci were examined by US, macroscopically and microscopically,
      using the microscopic analysis as the gold standard for CPP deposition. RESULTS:
      11 menisci of 6 patients have been studied. Ex vivo examination of menisci
      performed better in CPP identification than in vivo examination. The possible
      reasons of misinterpretation or misdiagnosis of the in vivo exam were identified
      and are extensively described in the paper. Also a new sign of CPP crystal
      deposits was found. CONCLUSIONS: This study permitted to highlight some
      difficulties in CPP crystal detection by US in menisci. Further studies are
      needed to define completely US CPP crystal aspect and to improve the sensibility
      and specificity of US in CPP deposition diagnosis.

PMID- 23970831
TI  - Preparation and cyclodextrin solubilization of the antibacterial agent benzoyl
      metronidazole.
AB  - A one-pot method for the preparation of benzoyl metronidazole was achieved by
      using N,N'-carbonyldiimidazole as a coupling reagent. Moreover, it was found that
      the byproduct imidazole as the catalyst promoted the reaction. In addition, the
      beta-cyclodextrin solubilization of benzoyl metronidazole was investigated by
      phase-solubility method. The phase-solubility studies indicated that the
      solubility of benzoyl metronidazole (S = 0.1435 g/L) was substantially increased
      9.7-fold (S' = 1.3881 g/L) by formation of 1 : 1 benzoyl metronidazole/beta
      cyclodextrin complexes in water, and the association constant K(a) value was
      determined to be 251 (+/-23) dm(3)/mol. Therefore, beta-cyclodextrin can work as
      a pharmaceutical solubilizer for benzoyl metronidazole and may improve its oral
      bioavailability.

PMID- 23970830
TI  - Molecular characterization of the porcine group A rotavirus NSP2 and NSP5/6 genes
      from Sao Paulo State, Brazil, in 2011/12.
AB  - Rotaviruses are responsible for the acute diarrhea in various mammalian and avian
      species. The nonstructural proteins NSP2 and NSP5 are involved in the rotavirus
      replication and the formation of viroplasm, cytoplasmic inclusion bodies within
      which new viral particles morphogenesis and viral RNA replication occur. There
      are few studies on the genetic diversity of those proteins; thus this study aims
      at characterizing the diversity of rotavirus based on NSP2 and NSP5 genes in
      rotaviruses circulating in Brazilian pig farms. For this purpose, 63 fecal
      samples from pig farms located in six different cities in the Sao Paulo State,
      Brazil, were screened by nested RT-PCR. Seven strains had the partial nucleotide
      sequencing for NSP2, whereas in six, the total sequencing for NSP5. All were
      characterized as genotype H1 and N1. The nucleotide identity of NSP2 genes ranged
      from 100% to 86.4% and the amino acid identity from 100% to 91.5%. For NSP5, the
      nucleotide identity was from 100% to 95.1% and the amino acid identity from 100%
      to 97.4%. It is concluded that the genotypes of the strains circulating in the
      region of study are in agreement with those reported in the literature for swine
      and that there is the possibility of interaction between human and animal
      rotaviruses. 

PMID- 23970832
TI  - The influence of 1-triacontanol on the growth, flowering, and quality of potted
      Bougainvillea plants (Bougainvillea glabra var. "Elizabeth Angus") under natural
      conditions.
AB  - Selected physiological and biochemical parameters were monitored at the
      vegetative and reproductive growth stages in potted Bougainvillea plants treated
      with five different concentrations of TRIA. Advanced flowering, flower bud
      number, and blooming rate increased significantly with 0.5 and 1.0 mg/L TRIA
      treatments. Similarly, photosynthetic rate, pigment content, quantum yield, and
      stomatal conductance increased significantly with 2.5, 1.0, and 5.0 mg/L TRIA
      treatments. Higher levels of N, P, and K, as well as increased total soluble
      solids (TSS) and higher sugar and protein contents, were recorded in treated
      plants. Furthermore, 46% more flowers, a 1.5-fold increase in bract weight,
      increased longevity, and 40% less leaf abscission were recorded following 2.5
      mg/L TRIA treatment. Phenol and flavonoid contents, sucrose phosphate synthase
      (SPS), and antioxidant activities were also markedly increased with 2.5 and 1.0
      mg/L TRIA treatments. However, ethylene production was significantly lower in the
      treated plants. Positive correlations were observed between leaf TSS and
      flowering time and flower number, between leaf sugar content and bract weight,
      and between net photosynthesis and bract growth and dry matter production. It can
      be concluded that the foliar spray of TRIA stimulates growth, enhances flowering,
      and improves the quality of potted Bougainvillea plants.

PMID- 23970833
TI  - Evaluation of the impacts of land use on water quality: a case study in the
      Chaohu Lake Basin.
AB  - It has been widely accepted that there is a close relationship between the land
      use type and water quality. There have been some researches on this relationship
      from the perspective of the spatial configuration of land use in recent years.
      This study aims to analyze the influence of various land use types on the water
      quality within the Chaohu Lake Basin based on the water quality monitoring data
      and RS data from 2000 to 2008, with the small watershed as the basic unit of
      analysis. The results indicated that there was significant negative correlation
      between forest land and grassland and the water pollution, and the built-up area
      had negative impacts on the water quality, while the influence of the cultivated
      land on the water quality was very complex. Besides, the impacts of the landscape
      diversity on the indicators of water quality within the watershed were also
      analyzed, the result of which indicated there was a significant negative
      relationship between them. The results can provide important scientific reference
      for the local land use optimization and water pollution control and guidance for
      the formulation of policies to coordinate the exploitation and protection of the
      water resource. 

PMID- 23970834
TI  - Koopmans' analysis of chemical hardness with spectral-like resolution.
AB  - Three approximation levels of Koopmans' theorem are explored and applied: the
      first referring to the inner quantum behavior of the orbitalic energies that
      depart from the genuine ones in Fock space when the wave-functions' Hilbert
      Banach basis set is specified to solve the many-electronic spectra of spin
      orbitals' eigenstates; it is the most subtle issue regarding Koopmans' theorem as
      it brings many critics and refutation in the last decades, yet it is shown here
      as an irrefutable "observational" effect through computation, specific to any in
      silico spectra of an eigenproblem; the second level assumes the "frozen spin
      orbitals" approximation during the extracting or adding of electrons to the
      frontier of the chemical system through the ionization and affinity processes,
      respectively; this approximation is nevertheless workable for great deal of
      chemical compounds, especially organic systems, and is justified for chemical
      reactivity and aromaticity hierarchies in an homologue series; the third and the
      most severe approximation regards the extension of the second one to superior
      orders of ionization and affinities, here studied at the level of chemical
      hardness compact-finite expressions up to spectral-like resolution for a
      paradigmatic set of aromatic carbohydrates. 

PMID- 23970835
TI  - Recent developments of electrochemical promotion of catalysis in the techniques
      of DeNOx.
AB  - Electrochemical promotion of catalysis reactions (EPOC) is one of the most
      significant discoveries in the field of catalytic and environmental protection.
      The work presented in this paper focuses on the aspects of reaction mechanism,
      influencing factors, and recent positive results. It has been shown with more
      than 80 different catalytic systems that the catalytic activity and selectivity
      of conductive catalysts deposited on solid electrolytes can be altered in the
      last 30 years. The active ingredient of catalyst can be activated by applying
      constant voltage or constant current to the catalysts/electrolyte interface. The
      effect of EPOC can improve greatly the conversion rate of NOx. And it can also
      improve the lifetime of catalyst by inhibiting its poisoning. 

PMID- 23970836
TI  - Presence service in IMS.
AB  - This paper describes the presence service, which is located in the IP multimedia
      subsystem. This service allows making many applications for different groups of
      people. The paper describes differences between a network without the service and
      with the service. The biggest change is an increased number of transmitted
      messages. The presence uses some part of the IP multimedia subsystem control
      layer, which is shown in communication between the user and the server. The paper
      deals with the number of generated messages depending on the behaviour of the
      users. This is described by a mathematical model using discrete Markov chains. 

PMID- 23970837
TI  - On Satnoianu-Wu's inequality.
AB  - By applying techniques in the theory of convex functions and Schur-geometrically
      convex functions, the author investigates a conjecture of Satnoianu on an
      algebraic inequality and generalizes some known results in recent years. 

PMID- 23970838
TI  - Smallpox still haunts scientists: results of a questionnaire-based inquiry on the
      views of health care and life science experts and students on preserving the
      remaining variola virus stocks.
AB  - The World Health Organization (WHO) declared eradication of the dreadful disease
      "smallpox" in 1980. Though the disease has died down, the causative virus
      "variola" has not, as it has been well preserved in two high security
      laboratories-one in USA and another in Russia. The debate on whether the
      remaining stocks of the smallpox virus should be destroyed or not is ongoing, and
      the World Health Assembly (WHA) in 2011 has decided to postpone the review on
      this debate to the 67th WHA in 2014. A short questionnaire-based inquiry was
      organized during a one-day stem cell meeting to explore the views of various
      health care and life science specialists especially students on this aspect.
      Among the 200 participants of the meeting, only 66 had answered the
      questionnaire. 60.6% of participants who responded to the questionnaire were for
      preserving the virus for future reference, while 36.4% of the participants were
      for destroying the virus considering the magnitude with which it killed millions.
      However, 3% of the respondents were not able to decide on any verdict. Therefore,
      this inquiry expresses the view that "what we cannot create, we do not have the
      right to destroy." 

PMID- 23970839
TI  - Calculating the energy spectrum of complex low-dimensional heterostructures in
      the electric field.
AB  - An algorithm for solving the steady-state Schrodinger equation for a complex
      piecewise-constant potential in the presence of the E-field is developed and
      implemented. The algorithm is based on the consecutive matching of solutions
      given by the Airy functions at the band boundaries with the matrix rank
      increasing by no more than two orders, which enables the characteristic solution
      to be obtained in the convenient form for search of the roots. The algorithm
      developed allows valid solutions to be obtained for the electric field magnitudes
      larger than the ground-state energy level, that is, when the perturbation method
      is not suitable. 

PMID- 23970840
TI  - Investigation on the achievable flow length in injection moulding of polymeric
      materials with dynamic mould tempering.
AB  - A variety of parts in microsystems technology are manufactured by injection
      moulding of polymeric materials. In Particular the high cooling velocity affects
      negatively the process and the resulting part properties. The scope of this paper
      is to investigate the influence on the reachable flow length in injection
      moulding of different polymeric materials. The results indicate that the mould
      temperature has less impact on the achievable flow length of the polymer melt as
      the injection pressure. A higher mould temperature leads only to a slight
      increase in flow length. In addition, a transcending of the glass or the
      crystallization temperature of polymeric materials with the mould temperature
      shows no effect on the achievable flow length of the material. 

PMID- 23970841
TI  - Optimizing instruction scheduling and register allocation for register-file
      connected clustered VLIW architectures.
AB  - Clustering has become a common trend in very long instruction words (VLIW)
      architecture to solve the problem of area, energy consumption, and design
      complexity. Register-file-connected clustered (RFCC) VLIW architecture uses the
      mechanism of global register file to accomplish the inter-cluster data
      communications, thus eliminating the performance and energy consumption penalty
      caused by explicit inter-cluster data move operations in traditional bus
      connected clustered (BCC) VLIW architecture. However, the limit number of access
      ports to the global register file has become an issue which must be well
      addressed; otherwise the performance and energy consumption would be harmed. In
      this paper, we presented compiler optimization techniques for an RFCC VLIW
      architecture called Lily, which is designed for encryption systems. These
      techniques aim at optimizing performance and energy consumption for Lily
      architecture, through appropriate manipulation of the code generation process to
      maintain a better management of the accesses to the global register file. All the
      techniques have been implemented and evaluated. The result shows that our
      techniques can significantly reduce the penalty of performance and energy
      consumption due to access port limitation of global register file. 

PMID- 23970842
TI  - On kth-order slant weighted Toeplitz operator.
AB  - Let beta = [formula: see text] be a sequence of positive numbers with beta0 = 1,
      0 < beta(n)/beta(n+1) <= 1 when n >= 0 and 0 < beta(n)/beta(n-1) <= 1 when n <=
      0. A kth-order slant weighted Toeplitz operator on L(2)(beta) is given by U(phi)
      = W(k)M(phi), where M(phi) is the multiplication on L(2)(beta) and W(k) is an
      operator on L(2)(beta) given by W(k)e(nk)(z) = (beta(n)/beta(nk))e(n)(z),
      [formula: see text] being the orthonormal basis for L(2)(beta). In this paper, we
      define a kth-order slant weighted Toeplitz matrix and characterise U(phi) in
      terms of this matrix. We further prove some properties of U(phi) using this
      characterisation.

PMID- 23970843
TI  - Optimized hyper beamforming of linear antenna arrays using collective animal
      behaviour.
AB  - A novel optimization technique which is developed on mimicking the collective
      animal behaviour (CAB) is applied for the optimal design of hyper beamforming of
      linear antenna arrays. Hyper beamforming is based on sum and difference beam
      patterns of the array, each raised to the power of a hyperbeam exponent
      parameter. The optimized hyperbeam is achieved by optimization of current
      excitation weights and uniform interelement spacing. As compared to conventional
      hyper beamforming of linear antenna array, real coded genetic algorithm (RGA),
      particle swarm optimization (PSO), and differential evolution (DE) applied to the
      hyper beam of the same array can achieve reduction in sidelobe level (SLL) and
      same or less first null beam width (FNBW), keeping the same value of hyperbeam
      exponent. Again, further reductions of sidelobe level (SLL) and first null beam
      width (FNBW) have been achieved by the proposed collective animal behaviour (CAB)
      algorithm. CAB finds near global optimal solution unlike RGA, PSO, and DE in the
      present problem. The above comparative optimization is illustrated through 10-,
      14-, and 20-element linear antenna arrays to establish the optimization efficacy
      of CAB. 

PMID- 23970844
TI  - Enhancement of antibacterial activity of capped silver nanoparticles in
      combination with antibiotics, on model gram-negative and gram-positive bacteria.
AB  - The nanoparticles used in this study were prepared from AgNO3 using NaBH4 in the
      presence of capping agents such as citrate, sodium dodecyl sulfate, and
      polyvinylpyrrolidone. The formed nanoparticles were characterized with UV-Vis,
      TEM, and XRD. The generation of silver nanoparticles was confirmed from the
      appearance of yellow colour and an absorption maximum between 399 and 404 nm. The
      produced nanoparticles were found to be spherical in shape and polydisperse. For
      citrate, SDS, and PVP capped nanoparticles, the average particle sizes were 38.3
      +/- 13.5, 19.3 +/- 6.0, and 16.0 +/- 4.8 nm, respectively. The crystallinity of
      the nanoparticles in FCC structure is confirmed from the SAED and XRD patterns.
      Also, the combined antibacterial activity of these differently capped
      nanoparticles with selected antibiotics (streptomycin, ampicillin, and
      tetracycline) was evaluated on model Gram-negative and Gram-positive bacteria,
      employing disc diffusion assay. The activity of the tested antibiotics was
      enhanced in combination with all the stabilized nanoparticles, against both the
      Gram classes of bacteria. The combined effects of silver nanoparticles and
      antibiotics were more prominent with PVP capped nanoparticles as compared to
      citrate and SDS capped ones. The results of this study demonstrate potential
      therapeutic applications of silver nanoparticles in combination with antibiotics.

PMID- 23970845
TI  - The Genetics of Obsessive-Compulsive Disorder.
AB  - OCD is a psychiatric disorder with a lifetime prevalence of 1-3% and is a
      significant cause of disability worldwide. Family studies indicate that OCD has a
      significant hereditable component, with relatives of OCD cases being 4 times more
      likely to develop the disorder than the general population. Linkage studies in
      OCD have generally been underpowered and have failed to reach the statistical
      threshold for genome-wide significance, but they have nevertheless been useful
      for revealing potential regions of interest for future candidate gene studies.
      Candidate gene studies in OCD have thus far focused on genes involved in the
      serotonergic, dopaminergic, and glutamatergic pathways. These studies have been
      for the most part inconclusive, and failures to replicate have been the norm
      until very recently. The only genetic association replicated by multiple groups
      was with a glutamate transporter gene (SLC1A1). Genome-wide association studies
      in OCD are in progress, but final results have not yet been reported. As with the
      study of many other psychiatric disorders, an improved understanding of OCD will
      only be achieved (1) with larger collaborative efforts involving more probands,
      (2) the use of probands and controls drawn from epidemiologically-based
      populations rather than clinical samples, (3) developing a more precise
      phenotypic description of OCD and (4) measuring important environmental
      influences that affect OCD pathogenesis and severity.

PMID- 23970847
TI  - Field resistance of Spodoptera litura (Lepidoptera: Noctuidae) to
      organophosphates, pyrethroids, carbamates and four newer chemistry insecticides
      in Hunan, China.
AB  - The present studies were carried out to evaluate resistance in the populations of
      Spodoptera litura Fab. (Lepidoptera, Noctuidae) from five districts of Hunan
      Province in China to various insecticides from 2010 to 2012 using a standard leaf
      dip bioassay method. For organophosphates and pyrethroids, resistance ratios
      compared with a susceptible Lab-BJ strain were in the range of 14-229-fold for
      organophosphates and 12-227-fold for pyrethroids. Similarly, relative low levels
      of resistance to emamectin, indoxacarb, and chlorfenapyr were observed in all
      five populations. In contrast, the resistance to carbamates (thiodicarb or
      methomyl) was significantly higher than that of organophosphates, pyrethroids and
      newer chemistry insecticides. The pairwise correlation coefficients of LC50
      values indicated that the newer chemistry insecticides and old generation
      insecticides were not significant except abamectin, which was negatively
      significantly correlated with methomyl. A significant correlation was observed
      between thiodicarb, methomyl, and deltamethrin, whereas resistance to bifenthrin
      showed no correlations with resistance to other insecticides except deltamethrin.
      The results are discussed in relation to integrated pest management for S. litura
      with special reference to management of field evolved resistance to insecticides.

PMID- 23970846
TI  - X-ray phase sensitive imaging methods: basic physical principles and potential
      medical applications.
AB  - Phase sensitive imaging theoretically allows for a drastic reduction in x-ray
      dose while simultaneously achieving comparable or better spatial and contrast
      resolution compared to traditional x-ray absorption based imaging. Several
      techniques exist to extract the phase information from an x-ray signal, including
      x-ray interferometry, diffraction enhanced imaging, in-line holography, coded
      aperture x-ray imaging, and grating-based interferometry. The physics of each
      method is reviewed, along with the potential clinical applications.

PMID- 23970848
TI  - Adult hippocampal neurogenesis inversely correlates with microglia in conditions
      of voluntary running and aging.
AB  - Adult hippocampal neurogenesis results in the formation of new neurons and is a
      process of brain plasticity involved in learning and memory. The proliferation of
      adult neural stem or progenitor cells is regulated by several extrinsic factors
      such as experience, disease or aging and intrinsic factors originating from the
      neurogenic niche. Microglia is very abundant in the dentate gyrus (DG) and
      increasing evidence indicates that these cells mediate the inflammation-induced
      reduction in neurogenesis. However, the role of microglia in neurogenesis in
      physiological conditions remains poorly understood. In this study, we monitored
      microglia and the proliferation of adult hippocampal stem/progenitor cells in
      physiological conditions known to increase or decrease adult neurogenesis,
      voluntary running and aging respectively. We found that the number of microglia
      in the DG was strongly inversely correlated with the number of stem/progenitor
      cells and cell proliferation in the granule cell layer. Accordingly, co-cultures
      of decreasing neural progenitor/glia ratio showed that microglia but not
      astroglia reduced the number of progenitor cells. Together, these results suggest
      that microglia inhibits the proliferation of neural stem/progenitor cells despite
      the absence of inflammatory stimulus. 

PMID- 23970849
TI  - The chronometry of risk processing in the human cortex.
AB  - The neuroscience of human decision-making has focused on localizing brain
      activity correlating with decision variables and choice, most commonly using
      functional MRI (fMRI). Poor temporal resolution means these studies are agnostic
      in relation to how decisions unfold in time. Consequently, here we address the
      temporal evolution of neural activity related to encoding of risk using
      magnetoencephalography (MEG), and show modulations of electromagnetic power in
      posterior parietal and dorsomedial prefrontal cortex (DMPFC) which scale with
      both variance and skewness in a lottery, detectable within 500 ms following
      stimulus presentation. Electromagnetic responses in somatosensory cortex
      following this risk encoding predict subsequent choices. Furthermore, within
      anterior insula we observed early and late effects of subject-specific risk
      preferences, suggestive of a role in both risk assessment and risk anticipation
      during choice. The observation that cortical activity tracks specific and
      independent components of risk from early time-points in a decision-making task
      supports the hypothesis that specialized brain circuitry underpins risk
      perception. 

PMID- 23970851
TI  - Classifying visuomotor workload in a driving simulator using subject specific
      spatial brain patterns.
AB  - A passive Brain Computer Interface (BCI) is a system that responds to the
      spontaneously produced brain activity of its user and could be used to develop
      interactive task support. A human-machine system that could benefit from brain
      based task support is the driver-car interaction system. To investigate the
      feasibility of such a system to detect changes in visuomotor workload, 34 drivers
      were exposed to several levels of driving demand in a driving simulator. Driving
      demand was manipulated by varying driving speed and by asking the drivers to
      comply to individually set lane keeping performance targets. Differences in the
      individual driver's workload levels were classified by applying the Common
      Spatial Pattern (CSP) and Fisher's linear discriminant analysis to frequency
      filtered electroencephalogram (EEG) data during an off line classification study.
      Several frequency ranges, EEG cap configurations, and condition pairs were
      explored. It was found that classifications were most accurate when based on high
      frequencies, larger electrode sets, and the frontal electrodes. Depending on
      these factors, classification accuracies across participants reached about 95% on
      average. The association between high accuracies and high frequencies suggests
      that part of the underlying information did not originate directly from neuronal
      activity. Nonetheless, average classification accuracies up to 75-80% were
      obtained from the lower EEG ranges that are likely to reflect neuronal activity.
      For a system designer, this implies that a passive BCI system may use several
      frequency ranges for workload classifications. 

PMID- 23970850
TI  - Coordinate transformation approach to social interactions.
AB  - A coordinate transformation framework for understanding how neurons compute
      sensorimotor behaviors has generated significant advances toward our
      understanding of basic brain function. This influential scaffold focuses on
      neuronal encoding of spatial information represented in different coordinate
      systems (e.g., eye-centered, hand-centered) and how multiple brain regions
      partake in transforming these signals in order to ultimately generate a motor
      output. A powerful analogy can be drawn from the coordinate transformation
      framework to better elucidate how the nervous system computes cognitive variables
      for social behavior. Of particular relevance is how the brain represents
      information with respect to oneself and other individuals, such as in reward
      outcome assignment during social exchanges, in order to influence social
      decisions. In this article, I outline how the coordinate transformation framework
      can help guide our understanding of neural computations resulting in social
      interactions. Implications for numerous psychiatric disorders with impaired
      representations of self and others are also discussed. 

PMID- 23970852
TI  - Long-term optical stimulation of channelrhodopsin-expressing neurons to study
      network plasticity.
AB  - Neuronal plasticity produces changes in excitability, synaptic transmission, and
      network architecture in response to external stimuli. Network adaptation to
      environmental conditions takes place in time scales ranging from few seconds to
      days, and modulates the entire network dynamics. To study the network response to
      defined long-term experimental protocols, we setup a system that combines optical
      and electrophysiological tools embedded in a cell incubator. Primary hippocampal
      neurons transduced with lentiviruses expressing channelrhodopsin-2/H134R were
      subjected to various photostimulation protocols in a time window in the order of
      days. To monitor the effects of light-induced gating of network activity,
      stimulated transduced neurons were simultaneously recorded using multi-electrode
      arrays (MEAs). The developed experimental model allows discerning short-term,
      long-lasting, and adaptive plasticity responses of the same neuronal network to
      distinct stimulation frequencies applied over different temporal windows. 

PMID- 23970853
TI  - Cortical region-specific engraftment of embryonic stem cell-derived neural
      progenitor cells restores axonal sprouting to a subcortical target and achieves
      motor functional recovery in a mouse model of neonatal hypoxic-ischemic brain
      injury.
AB  - Hypoxic-ischemic encephalopathy (HIE) at birth could cause cerebral palsy (CP),
      mental retardation, and epilepsy, which last throughout the individual's
      lifetime. However, few restorative treatments for ischemic tissue are currently
      available. Cell replacement therapy offers the potential to rescue brain damage
      caused by HI and to restore motor function. In the present study, we evaluated
      the ability of embryonic stem cell-derived neural progenitor cells (ES-NPCs) to
      become cortical deep layer neurons, to restore the neural network, and to repair
      brain damage in an HIE mouse model. ES cells stably expressing the reporter gene
      GFP are induced to a neural precursor state by stromal cell co-culture. Forty
      hours after the induction of HIE, animals were grafted with ES-NPCs targeting the
      deep layer of the motor cortex in the ischemic brain. Motor function was
      evaluated 3 weeks after transplantation. Immunohistochemistry and neuroanatomical
      tracing with GFP were used to analyze neuronal differentiation and axonal
      sprouting. ES-NPCs could differentiate to cortical neurons with pyramidal
      morphology and expressed the deep layer-specific marker, Ctip2. The graft showed
      good survival and an appropriate innervation pattern via axonal sprouting from
      engrafted cells in the ischemic brain. The motor functions of the transplanted
      HIE mice also improved significantly compared to the sham-transplanted group.
      These findings suggest that cortical region specific engraftment of
      preconditioned cortical precursor cells could support motor functional recovery
      in the HIE model. It is not clear whether this is a direct effect of the
      engrafted cells or due to neurotrophic factors produced by these cells. These
      results suggest that cortical region-specific NPC engraftment is a promising
      therapeutic approach for brain repair. 

PMID- 23970854
TI  - Disruption of cerebellar microzonal organization in GluD2 (GluRdelta2) knockout
      mouse.
AB  - Cerebellar cortex has an elaborate rostrocaudal organization comprised of
      numerous microzones. Purkinje cells (PCs) in the same microzone show synchronous
      activity of complex spikes (CSs) evoked by excitatory inputs from climbing fibers
      (CFs) that arise from neurons in the inferior olive (IO). The synchronous CS
      activity is considered to depend on electrical coupling among IO neurons and
      anatomical organization of the olivo-cerebellar projection. To determine how the
      CF-PC wiring contributes to the formation of microzone, we examined the
      synchronous CS activities between neighboring PCs in the glutamate receptor
      delta2 knockout (GluD2 KO) mouse in which exuberant surplus CFs make ectopic
      innervations onto distal dendrites of PCs. We performed in vivo two-photon
      calcium imaging for PC populations to detect CF inputs. Neighboring PCs in GluD2
      KO mice showed higher synchrony of calcium transients than those in wild-type
      (control) mice. Moreover, the synchrony in GluD2 KO mice hardly declined with
      mediolateral separation between PCs up to ~200 MUm, which was in marked contrast
      to the falloff of the synchrony in control mice. The enhanced synchrony was only
      partially affected by the blockade of gap junctional coupling. On the other hand,
      transverse CF collaterals in GluD2 KO mice extended beyond the border of
      microzone and formed locally clustered ectopic synapses onto dendrites of
      neighboring PCs. Furthermore, PCs in GluD2 KO mice exhibited clustered firing
      (Cf), the characteristic CF response that was not found in PCs of wild-type mice.
      Importantly, Cf was often associated with localized calcium transients in distal
      dendrites of PCs, which are likely to contribute to the enhanced synchrony of
      calcium signals in GluD2 KO mice. Thus, our results indicate that CF signals in
      GluD2 KO mice propagate across multiple microzones, and that proper formation of
      longitudinal olivo-cerebellar projection is essential for the spatiotemporal
      organization of CS activity in the cerebellum. 

PMID- 23970855
TI  - Strength and timing of motor responses mediated by rebound firing in the
      cerebellar nuclei after Purkinje cell activation.
AB  - The cerebellum refines the accuracy and timing of motor performance. How it
      encodes information to perform these functions is a major topic of interest. We
      performed whole cell and extracellular recordings of Purkinje cells (PCs) and
      cerebellar nuclei neurons (CNs) in vivo, while activating PCs with light in
      transgenic mice. We show for the first time that graded activation of PCs
      translates into proportional CN inhibition and induces rebound activity in CNs,
      which is followed by graded motor contractions timed to the cessation of the
      stimulus. Moreover, activation of PC ensembles led to disinhibition of climbing
      fiber activity, which coincided with rebound activity in CNs. Our data indicate
      that cessation of concerted activity in ensembles of PCs can regulate both timing
      and strength of movements via control of rebound activity in CNs. 

PMID- 23970856
TI  - Eye movement related brain responses to emotional scenes during free viewing.
AB  - Emotional stimuli are preferentially processed over neutral stimuli. Previous
      studies, however, disagree on whether emotional stimuli capture attention
      preattentively or whether the processing advantage is dependent on allocation of
      attention. The present study investigated attention and emotion processes by
      measuring brain responses related to eye movement events while 11 participants
      viewed images selected from the International Affective Picture System (IAPS).
      Brain responses to emotional stimuli were compared between serial and parallel
      presentation. An "emotional" set included one image with high positive or
      negative valence among neutral images. A "neutral" set comprised four neutral
      images. The participants were asked to indicate which picture-if any-was
      emotional and to rate that picture on valence and arousal. In the serial
      condition, the event-related potentials (ERPs) were time-locked to the stimulus
      onset. In the parallel condition, the ERPs were time-locked to the first eye
      entry on an image. The eye movement results showed facilitated processing of
      emotional, especially unpleasant information. The EEG results in both
      presentation conditions showed that the LPP ("late positive potential")
      amplitudes at 400-500 ms were enlarged for the unpleasant and pleasant pictures
      as compared to neutral pictures. Moreover, the unpleasant scenes elicited
      stronger responses than pleasant scenes. The ERP results did not support
      parafoveal emotional processing, although the eye movement results suggested
      faster attention capture by emotional stimuli. Our findings, thus, suggested that
      emotional processing depends on overt attentional resources engaged in the
      processing of emotional content. The results also indicate that brain responses
      to emotional images can be analyzed time-locked to eye movement events, although
      the response amplitudes were larger during serial presentation. 

PMID- 23970857
TI  - Neural correlates of auditory temporal predictions during sensorimotor
      synchronization.
AB  - Musical ensemble performance requires temporally precise interpersonal action
      coordination. To play in synchrony, ensemble musicians presumably rely on
      anticipatory mechanisms that enable them to predict the timing of sounds produced
      by co-performers. Previous studies have shown that individuals differ in their
      ability to predict upcoming tempo changes in paced finger-tapping tasks (indexed
      by cross-correlations between tap timing and pacing events) and that the degree
      of such prediction influences the accuracy of sensorimotor synchronization (SMS)
      and interpersonal coordination in dyadic tapping tasks. The current functional
      magnetic resonance imaging study investigated the neural correlates of auditory
      temporal predictions during SMS in a within-subject design. Hemodynamic responses
      were recorded from 18 musicians while they tapped in synchrony with auditory
      sequences containing gradual tempo changes under conditions of varying cognitive
      load (achieved by a simultaneous visual n-back working-memory task comprising
      three levels of difficulty: observation only, 1-back, and 2-back object
      comparisons). Prediction ability during SMS decreased with increasing cognitive
      load. Results of a parametric analysis revealed that the generation of auditory
      temporal predictions during SMS recruits (1) a distributed network of cortico
      cerebellar motor-related brain areas (left dorsal premotor and motor cortex,
      right lateral cerebellum, SMA proper and bilateral inferior parietal cortex) and
      (2) medial cortical areas (medial prefrontal cortex, posterior cingulate cortex).
      While the first network is presumably involved in basic sensory prediction,
      sensorimotor integration, motor timing, and temporal adaptation, activation in
      the second set of areas may be related to higher-level social-cognitive processes
      elicited during action coordination with auditory signals that resemble music
      performed by human agents. 

PMID- 23970858
TI  - Comparison of the neural correlates of encoding item-item and item-context
      associations.
AB  - fMRI was employed to investigate the role of the left inferior frontal gyrus
      (LIFG) in the encoding of item-item and item-context associations. On each of a
      series of study trials subjects viewed a picture that was presented either to the
      left or right of fixation, along with a subsequently presented word that appeared
      at fixation. Memory was tested in a subsequent memory test that took place
      outside of the scanner. On each test trial one of two forced choice judgments was
      required. For the associative test, subjects chose between the word paired with
      the picture at study and a word studied on a different trial. For the source
      test, the judgment was whether the picture had been presented on the left or
      right. Successful encoding of associative information was accompanied by
      subsequent memory effects in several cortical regions, including much of the
      LIFG. By contrast, successful source encoding was selectively associated with a
      subsequent memory effect in right fusiform cortex. The finding that the LIFG was
      enhanced during successful associative, but not source, encoding is interpreted
      in light of the proposal that subsequent memory effects are localized to cortical
      regions engaged by the on-line demands of the study task. 

PMID- 23970859
TI  - Mental practice promotes motor anticipation: evidence from skilled music
      performance.
AB  - Mental practice (MP) has been shown to improve movement accuracy and velocity,
      but it is not known whether MP can also optimize movement timing. We addressed
      this question by studying two groups of expert pianists who performed challenging
      music sequences after either MP or physical practice (PP). Performance and motion
      capture data were collected along with responses to imagery questionnaires. The
      results showed that MP produced performance improvements, although to a lower
      degree than PP did. MP and PP induced changes in both movement velocity and
      movement timing, promoting the emergence of movement anticipatory patterns.
      Furthermore, motor imagery was associated with greater changes in movement
      velocity, while auditory imagery was associated with greater movement
      anticipation. Data from a control group that was not allowed to practice
      confirmed that the changes in accuracy and kinematics were not due to mere
      repetition of the sequence during testing. This study provides the first evidence
      of an anticipatory control following MP and extends the present knowledge on the
      effectiveness of MP to a task of unparalleled motor complexity. The practical
      implications of MP in the motor domain are discussed. 

PMID- 23970861
TI  - Neuropathologies of the self and the right hemisphere: a window into productive
      personal pathologies.

PMID- 23970860
TI  - Characterizing aging in the human brainstem using quantitative multimodal MRI
      analysis.
AB  - Aging is ubiquitous to the human condition. The MRI correlates of healthy aging
      have been extensively investigated using a range of modalities, including
      volumetric MRI, quantitative MRI (qMRI), and diffusion tensor imaging. Despite
      this, the reported brainstem related changes remain sparse. This is, in part, due
      to the technical and methodological limitations in quantitatively assessing and
      statistically analyzing this region. By utilizing a new method of brainstem
      segmentation, a large cohort of 100 healthy adults were assessed in this study
      for the effects of aging within the human brainstem in vivo. Using qMRI, tensor
      based morphometry (TBM), and voxel-based quantification (VBQ), the volumetric and
      quantitative changes across healthy adults between 19 and 75 years were
      characterized. In addition to the increased R2* in substantia nigra corresponding
      to increasing iron deposition with age, several novel findings were reported in
      the current study. These include selective volumetric loss of the brachium
      conjunctivum, with a corresponding decrease in magnetization transfer and
      increase in proton density (PD), accounting for the previously described
      "midbrain shrinkage." Additionally, we found increases in R1 and PD in several
      pontine and medullary structures. We consider these changes in the context of
      well-characterized, functional age-related changes, and propose potential
      biophysical mechanisms. This study provides detailed quantitative analysis of the
      internal architecture of the brainstem and provides a baseline for further
      studies of neurodegenerative diseases that are characterized by early, pre
      clinical involvement of the brainstem, such as Parkinson's and Alzheimer's
      diseases. 

PMID- 23970862
TI  - Training approach-avoidance of smiling faces affects emotional vulnerability in
      socially anxious individuals.
AB  - PREVIOUS RESEARCH REVEALED AN AUTOMATIC BEHAVIORAL BIAS IN HIGH SOCIALLY ANXIOUS
      INDIVIDUALS (HSAS): although their explicit evaluations of smiling faces are
      positive, they show automatic avoidance of these faces. This is reflected by
      faster pushing than pulling of smiling faces in an Approach-Avoidance Task (AAT;
      Heuer et al., 2007). The current study addressed the causal role of this
      avoidance bias for social anxiety. To this end, we used the AAT to train HSAs,
      either to approach smiling faces or to avoid them. We examined whether such an
      AAT training could change HSAs' automatic avoidance tendencies, and if yes,
      whether AAT effects would generalize to a new approach task with new facial
      stimuli, and to mood and anxiety in a social threat situation (a video-recorded
      self-presentation). We found that HSAs trained to approach smiling faces did
      indeed approach female faces faster after the training than HSAs trained to avoid
      smiling faces. Moreover, approach-faces training reduced emotional vulnerability:
      it led to more positive mood and lower anxiety after the self-presentation than
      avoid-faces training. These results suggest that automatic approach-avoidance
      tendencies have a causal role in social anxiety, and that they can be modified by
      a simple computerized training. This may open new avenues in the therapy of
      social phobia. 

PMID- 23970863
TI  - Addressing social resistance in emerging security technologies.
AB  - In their efforts to enhance the safety and security of citizens, governments and
      law enforcement agencies look to scientists and engineers to produce modern
      methods for preventing, detecting, and prosecuting criminal activities. Whole
      body scanners, lie detection technologies, biometrics, etc., are all being
      developed for incorporation into the criminal justice apparatus. Yet despite
      their purported security benefits these technologies often evoke social
      resistance. Concerns over privacy, ethics, and function-creep appear repeatedly
      in analyses of these technologies. It is argued here that scientists and
      engineers continue to pay insufficient attention to this resistance;
      acknowledging the presence of these social concerns yet failing to meaningfully
      address them. In so doing they place at risk the very technologies and techniques
      they are seeking to develop, for socially controversial security technologies
      face restrictions and in some cases outright banning. By identifying sources of
      potential social resistance early in the research and design process, scientists
      can both engage with the public in meaningful debate and modify their security
      technologies before deployment so as to minimize social resistance and enhance
      uptake. 

PMID- 23970864
TI  - Impact of neuronal heterogeneity on correlated colored noise-induced
      synchronization.
AB  - Synchronization plays an important role in neural signal processing and
      transmission. Many hypotheses have been proposed to explain the origin of neural
      synchronization. In recent years, correlated noise-induced synchronization has
      received support from many theoretical and experimental studies. However, many of
      these prior studies have assumed that neurons have identical biophysical
      properties and that their inputs are well modeled by white noise. In this
      context, we use colored noise to induce synchronization between oscillators with
      heterogeneity in both phase-response curves and frequencies. In the low noise
      limit, we derive novel analytical theory showing that the time constant of
      colored noise influences correlated noise-induced synchronization and that
      oscillator heterogeneity can limit synchronization. Surprisingly, however,
      heterogeneous oscillators may synchronize better than homogeneous oscillators
      given low input correlations. We also find resonance of oscillator
      synchronization to colored noise inputs when firing frequencies diverge.
      Collectively, these results prove robust for both relatively high noise regimes
      and when applied to biophysically realistic spiking neuron models, and further
      match experimental recordings from acute brain slices. 

PMID- 23970865
TI  - Development of antibody arrays for monoclonal antibody Higher Order Structure
      analysis.
AB  - Antibody arrays were developed to probe a monoclonal antibody's three-dimensional
      structure (3-D structure). Peptides with overlapping regions were designed to
      cover the whole mAb light chain and heavy chain, respectively, and used to
      generate polyclonal antibodies after the conjugation of the peptides to a carrier
      protein, KLH. It was shown that good peptide specificity was achieved from the
      antibodies generated. Using more than 30 different polyclonal antibodies to
      measure the surface epitope distribution, it was shown that the mAb antibody
      array can detect epitope exposure as low as 0.1% of defined mAb populations. This
      ELISA-based analysis of mAb epitope exposure can be considered as a measurement
      of "conformational impurity" in biologics development, similar to the analysis of
      other product-related impurities such as different forms of glycosylation,
      deamidation, and oxidation. This analysis of "conformational impurity" could
      provide valuable information on the mAb conformational comparability for
      biosimilar mAbs as well as novel mAbs, especially in the area of protein
      immunogenicity. Furthermore, stability studies indicated that there are several
      conformational "hot spots" in many mAbs tested, especially in the hinge region.
      This antibody array technology can be used for novel mAb Higher Order Structure
      (HOS) analysis during process and formulation development. Another important area
      of application is for biosimilar mAb development where the innovator molecule and
      biosimilar molecule could be compared based on their systemic "fingerprint" from
      the 30 plus antibodies. 

PMID- 23970866
TI  - K(+) channels and cell cycle progression in tumor cells.
AB  - K(+) ions play a major role in many cellular processes. The deregulation of K(+)
      signaling is associated with a variety of diseases such as hypertension,
      atherosclerosis, or diabetes. K(+) ions are important for setting the membrane
      potential, the driving force for Ca(2+) influx, and regulate volume of growing
      cells. Moreover, it is increasingly recognized that K(+) channels control cell
      proliferation through a novel signaling mechanisms triggered and modulated
      independently of ion fluxes. In cancer, aberrant expression, regulation and/or
      sublocalization of K(+) channels can alter the downstream signals that converge
      on the cell cycle machinery. Various K(+) channels are involved in cell cycle
      progression and are needed only at particular stages of the cell cycle.
      Consistent with this idea, the expression of Eag1 and HERG channels fluctuate
      along the cell cycle. Despite of acquired knowledge, our understanding of K(+)
      channels functioning in cancer cells requires further studies. These include
      identifying the molecular mechanisms controlling the cell cycle machinery. By
      understanding how K(+) channels regulate cell cycle progression in cancer cells,
      we will gain insights into how cancer cells subvert the need for K(+) signal and
      its downstream targets to proliferate. 

PMID- 23970868
TI  - Integrating probabilistic models of perception and interactive neural networks: a
      historical and tutorial review.
AB  - This article seeks to establish a rapprochement between explicitly Bayesian
      models of contextual effects in perception and neural network models of such
      effects, particularly the connectionist interactive activation (IA) model of
      perception. The article is in part an historical review and in part a tutorial,
      reviewing the probabilistic Bayesian approach to understanding perception and how
      it may be shaped by context, and also reviewing ideas about how such
      probabilistic computations may be carried out in neural networks, focusing on the
      role of context in interactive neural networks, in which both bottom-up and top
      down signals affect the interpretation of sensory inputs. It is pointed out that
      connectionist units that use the logistic or softmax activation functions can
      exactly compute Bayesian posterior probabilities when the bias terms and
      connection weights affecting such units are set to the logarithms of appropriate
      probabilistic quantities. Bayesian concepts such the prior, likelihood, (joint
      and marginal) posterior, probability matching and maximizing, and calculating vs.
      sampling from the posterior are all reviewed and linked to neural network
      computations. Probabilistic and neural network models are explicitly linked to
      the concept of a probabilistic generative model that describes the relationship
      between the underlying target of perception (e.g., the word intended by a speaker
      or other source of sensory stimuli) and the sensory input that reaches the
      perceiver for use in inferring the underlying target. It is shown how a new
      version of the IA model called the multinomial interactive activation (MIA) model
      can sample correctly from the joint posterior of a proposed generative model for
      perception of letters in words, indicating that interactive processing is fully
      consistent with principled probabilistic computation. Ways in which these
      computations might be realized in real neural systems are also considered. 

PMID- 23970867
TI  - Dopaminergic dysregulation in prefrontal cortex of rhesus monkeys following
      cocaine self-administration.
AB  - Chronic cocaine administration regulates the expression of several proteins
      related to dopaminergic signaling and synaptic function in the mesocorticolimbic
      pathway, including the prefrontal cortex. Functional abnormalities in the
      prefrontal cortex are hypothesized to be due in part to the expression of
      proteins involved in dopamine signaling and plasticity. Adult male rhesus monkeys
      self-administered cocaine (i.v.) under limited (n = 4) and extended access
      conditions (n = 6). The abundance of surrogate markers of dopamine signaling and
      plasticity in the dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex
      (OFC), and anterior cingulate cortex (ACC) were examined: glycosylated and non
      glycosylated forms of the dopamine transporter (efficiency of dopamine
      transport), tyrosine hydroxylase (TH; marker of dopamine synthesis) and
      phosphorylated TH at Serine 30 and 40 (markers of enzyme activity), extracellular
      signal-regulated kinase 1 and 2 (ERK1 and ERK 2), and phosphorylated ERK1 and
      ERK2 (phosphorylates TH Serine 31; markers of synaptic plasticity), and markers
      of synaptic integrity, spinophilin and post-synaptic density protein 95 (roles in
      dopamine signaling and response to cocaine). Extended cocaine access increased
      non-glycosylated and glycosylated DAT in DLPFC and OFC. While no differences in
      TH expression were observed between groups for any of the regions, extended
      access induced significant elevations in pTH(Ser31) in all regions. In addition,
      a slight but significant reduction in phosphorylated pTH(Ser40) was found in the
      DLPFC. Phosphorylated ERK2 was increased in all regions; however, pERK1 was
      decreased in ACC and OFC but increased in DLPFC. PSD-95 was increased in the OFC
      but not in DLPFC or ACC. Furthermore, extended cocaine self-administration
      elicited significant increases in spinophilin protein expression in all regions.
      Results from the study provide insight into the biochemical alterations occurring
      in primate prefrontal cortex. 

PMID- 23970869
TI  - Modeling language and cognition with deep unsupervised learning: a tutorial
      overview.
AB  - Deep unsupervised learning in stochastic recurrent neural networks with many
      layers of hidden units is a recent breakthrough in neural computation research.
      These networks build a hierarchy of progressively more complex distributed
      representations of the sensory data by fitting a hierarchical generative model.
      In this article we discuss the theoretical foundations of this approach and we
      review key issues related to training, testing and analysis of deep networks for
      modeling language and cognitive processing. The classic letter and word
      perception problem of McClelland and Rumelhart (1981) is used as a tutorial
      example to illustrate how structured and abstract representations may emerge from
      deep generative learning. We argue that the focus on deep architectures and
      generative (rather than discriminative) learning represents a crucial step
      forward for the connectionist modeling enterprise, because it offers a more
      plausible model of cortical learning as well as a way to bridge the gap between
      emergentist connectionist models and structured Bayesian models of cognition. 

PMID- 23970870
TI  - Dyscalculia from a developmental and differential perspective.

PMID- 23970871
TI  - The naive language expert: introduction to the research topic.

PMID- 23970873
TI  - Using a staircase procedure for the objective measurement of auditory stream
      integration and segregation thresholds.
AB  - Auditory scene analysis describes the ability to segregate relevant sounds out
      from the environment and to integrate them into a single sound stream using the
      characteristics of the sounds to determine whether or not they are related. This
      study aims to contrast task performances in objective threshold measurements of
      segregation and integration using identical stimuli, manipulating two variables
      known to influence streaming, inter-stimulus-interval (ISI) and frequency
      difference (Deltaf). For each measurement, one parameter (either ISI or Deltaf)
      was held constant while the other was altered in a staircase procedure. By using
      this paradigm, it is possible to test within-subject across multiple conditions,
      covering a wide Deltaf and ISI range in one testing session. The objective tasks
      were based on across-stream temporal judgments (facilitated by integration) and
      within-stream deviance detection (facilitated by segregation). Results show the
      objective integration task is well suited for combination with the staircase
      procedure, as it yields consistent threshold measurements for separate variations
      of ISI and Deltaf, as well as being significantly related to the subjective
      thresholds. The objective segregation task appears less suited to the staircase
      procedure. With the integration-based staircase paradigm, a comprehensive
      assessment of streaming thresholds can be obtained in a relatively short space of
      time. This permits efficient threshold measurements particularly in groups for
      which there is little prior knowledge on the relevant parameter space for
      streaming perception. 

PMID- 23970872
TI  - Are patients with schizophrenia impaired in processing non-emotional features of
      human faces?
AB  - It is known that individuals with schizophrenia exhibit signs of impaired face
      processing, however, the exact perceptual and cognitive mechanisms underlying
      these deficits are yet to be elucidated. One possible source of confusion in the
      current literature is the methodological and conceptual inconsistencies that can
      arise from the varied treatment of different aspects of face processing relating
      to emotional and non-emotional aspects of face perception. This review aims to
      disentangle the literature by focusing on the performance of patients with
      schizophrenia in a range of tasks that required processing of non-emotional
      features of face stimuli (e.g., identity or gender). We also consider the
      performance of patients on non-face stimuli that share common elements such as
      familiarity (e.g., cars) and social relevance (e.g., gait). We conclude by
      exploring whether observed deficits are best considered as "face-specific" and
      note that further investigation is required to properly assess the potential
      contribution of more generalized attentional or perceptual impairments. 

PMID- 23970874
TI  - Schizophrenia spectrum participants have reduced visual contrast sensitivity to
      chromatic (red/green) and luminance (light/dark) stimuli: new insights into
      information processing, visual channel function, and antipsychotic effects.
AB  - BACKGROUND: Individuals with schizophrenia spectrum diagnoses have deficient
      visual information processing as assessed by a variety of paradigms including
      visual backward masking, motion perception and visual contrast sensitivity (VCS).
      In the present study, the VCS paradigm was used to investigate potential
      differences in magnocellular (M) vs. parvocellular (P) channel function that
      might account for the observed information processing deficits of schizophrenia
      spectrum patients. Specifically, VCS for near threshold luminance (black/white)
      stimuli is known to be governed primarily by the M channel, while VCS for near
      threshold chromatic (red/green) stimuli is governed by the P channel. METHODS:
      VCS for luminance and chromatic stimuli (counterphase-reversing sinusoidal
      gratings, 1.22 c/degree, 8.3 Hz) was assessed in 53 patients with schizophrenia
      (including 5 off antipsychotic medication), 22 individuals diagnosed with
      schizotypal personality disorder and 53 healthy comparison subjects. RESULTS:
      Schizophrenia spectrum groups demonstrated reduced VCS in both conditions
      relative to normals, and there was no significant group by condition interaction
      effect. Post-hoc analyses suggest that it was the patients with schizophrenia on
      antipsychotic medication as well as SPD participants who accounted for the
      deficits in the luminance condition. CONCLUSIONS: These results demonstrate
      visual information processing deficits in schizophrenia spectrum populations but
      do not support the notion of selective abnormalities in the function of
      subcortical channels as suggested by previous studies. Further work is needed in
      a longitudinal design to further assess VCS as a vulnerability marker for
      psychosis as well as the effect of antipsychotic agents on performance in
      schizophrenia spectrum populations.

PMID- 23970875
TI  - Pleasurable music affects reinforcement learning according to the listener.
AB  - Mounting evidence links the enjoyment of music to brain areas implicated in
      emotion and the dopaminergic reward system. In particular, dopamine release in
      the ventral striatum seems to play a major role in the rewarding aspect of music
      listening. Striatal dopamine also influences reinforcement learning, such that
      subjects with greater dopamine efficacy learn better to approach rewards while
      those with lesser dopamine efficacy learn better to avoid punishments. In this
      study, we explored the practical implications of musical pleasure through its
      ability to facilitate reinforcement learning via non-pharmacological dopamine
      elicitation. Subjects from a wide variety of musical backgrounds chose a
      pleasurable and a neutral piece of music from an experimenter-compiled database,
      and then listened to one or both of these pieces (according to pseudo-random
      group assignment) as they performed a reinforcement learning task dependent on
      dopamine transmission. We assessed musical backgrounds as well as typical
      listening patterns with the new Helsinki Inventory of Music and Affective
      Behaviors (HIMAB), and separately investigated behavior for the training and test
      phases of the learning task. Subjects with more musical experience trained better
      with neutral music and tested better with pleasurable music, while those with
      less musical experience exhibited the opposite effect. HIMAB results regarding
      listening behaviors and subjective music ratings indicate that these effects
      arose from different listening styles: namely, more affective listening in non
      musicians and more analytical listening in musicians. In conclusion, musical
      pleasure was able to influence task performance, and the shape of this effect
      depended on group and individual factors. These findings have implications in
      affective neuroscience, neuroaesthetics, learning, and music therapy. 

PMID- 23970876
TI  - Assessing sleep consciousness within subjects using a serial awakening paradigm.
AB  - Dreaming-a particular form of consciousness that occurs during sleep-undergoes
      major changes in the course of the night. We aimed to outline state-dependent
      features of consciousness using a paradigm with multiple serial
      awakenings/questionings that allowed for within as well as between subject
      comparisons. Seven healthy participants who spent 44 experimental study nights in
      the laboratory were awakened by a computerized sound at 15-30 min intervals,
      regardless of sleep stage, and questioned for the presence or absence of sleep
      consciousness. Recall without content ("I was experiencing something but do not
      remember what") was considered separately. Subjects had to indicate the content
      of the most recent conscious experience prior to the alarm sound and to estimate
      its duration and richness. We also assessed the degree of thinking and
      perceiving, self- and environment-relatedness and reflective consciousness of the
      experiences. Of the 778 questionings, 5% were performed during wakefulness, 2% in
      stage N1, 42% in N2, 33% in N3, and 17% in rapid eye movement (REM) sleep. Recall
      with content was reported in 34% of non-REM and in 77% of REM sleep awakenings.
      Sleep fragmentation inherent to the study design appeared to only minimally
      affect the recall of conscious experiences. Each stage displayed a unique
      combination of characteristic features of sleep consciousness. In conclusion, our
      serial awakening paradigm allowed us to collect a large and representative sample
      of conscious experiences across states of being. It represents a time-efficient
      method for the study of sleep consciousness that may prove particularly
      advantageous when combined with techniques such as functional MRI and high
      density EEG. 

PMID- 23970877
TI  - Spatial representations of numbers and letters in children.
AB  - Different lines of evidence suggest that children's mental representations of
      numbers are spatially organized in form of a mental number line. It is, however,
      still unclear whether a spatial organization is specific for the numerical domain
      or also applies to other ordinal sequences in children. In the present study,
      children (n = 129) aged 8-9 years were asked to indicate the midpoint of lines
      flanked by task-irrelevant digits or letters. We found that the localization of
      the midpoint was systematically biased toward the larger digit. A similar, but
      less pronounced, effect was detected for letters with spatial biases toward the
      letter succeeding in the alphabet. Instead of assuming domain-specific forms of
      spatial representations, we suggest that ordinal information expressing relations
      between different items of a sequence might be spatially coded in children,
      whereby numbers seem to convey this kind of information in the most salient way. 

PMID- 23970878
TI  - The influence of scene context on object recognition is independent of
      attentional focus.
AB  - Humans can quickly and accurately recognize objects within briefly presented
      natural scenes. Previous work has provided evidence that scene context
      contributes to this process, demonstrating improved naming of objects that were
      presented in semantically consistent scenes (e.g., a sandcastle on a beach)
      relative to semantically inconsistent scenes (e.g., a sandcastle on a football
      field). The current study was aimed at investigating which processes underlie the
      scene consistency effect. Specifically, we tested: (1) whether the effect is due
      to increased visual feature and/or shape overlap for consistent relative to
      inconsistent scene-object pairs; and (2) whether the effect is mediated by
      attention to the background scene. Experiment 1 replicated the scene consistency
      effect of a previous report (Davenport and Potter, 2004). Using a new, carefully
      controlled stimulus set, Experiment 2 showed that the scene consistency effect
      could not be explained by low-level feature or shape overlap between scenes and
      target objects. Experiments 3a and 3b investigated whether focused attention
      modulates the scene consistency effect. By using a location cueing manipulation,
      participants were correctly informed about the location of the target object on a
      proportion of trials, allowing focused attention to be deployed toward the target
      object. Importantly, the effect of scene consistency on target object recognition
      was independent of spatial attention, and was observed both when attention was
      focused on the target object and when attention was focused on the background
      scene. These results indicate that a semantically consistent scene context
      benefits object recognition independently of the focus of attention. We suggest
      that the scene consistency effect is primarily driven by global scene properties,
      or "scene gist", that can be processed with minimal attentional resources. 

PMID- 23970880
TI  - RAGE-Mediated Inflammation, Type 2 Diabetes, and Diabetic Vascular Complication.
AB  - Obesity is associated with inflammation and type 2 diabetes. Innate immune system
      comprised of cellular and molecular components plays an important role in the
      inflammatory reactions. Immune cells like macrophages and their cell surface
      pattern-recognition receptors (PRRs) are representative for innate immunity
      promoting inflammatory reactions. The receptor for advanced glycation end
      products (RAGE) is a member of PRRs and a proinflammatory molecular device that
      mediates danger signals to the body. The expression of RAGE is observed in
      adipocytes as well as immune cells, endothelial cells, and pancreatic beta cells
      under certain conditions. It has been reported that RAGE is implicated in
      adipocyte hypertrophy and insulin resistance. RAGE-mediated regulation of
      adiposity and inflammation may attribute to type 2 diabetes and diabetic vascular
      complications. 

PMID- 23970879
TI  - Clinical implications of adipocytokines and newly emerging metabolic factors with
      relation to insulin resistance and cardiovascular health.
AB  - Adipose tissue is known to secrete hormones actively and produces many
      biologically active proteins called adipocytokines. Typically, obesity is
      followed by low-grade inflammation, which is characterized by increased
      circulating levels of pro-inflammatory cytokines. Macrophages play a role in the
      inflammatory process by secreting many cytokines such as tumor necrosis factor
      alpha, interleukin-6, resistin, and retinol binding protein-4. These cytokines
      and chemokines participate in low-grade pro-inflammatory processes leading to
      insulin resistance, metabolic impairment, and cardiovascular diseases. More
      metabolic regulators, such as fibroblast growth factor (FGF)21, FGF19, FGF1,
      vaspin, and visfatin have now been discovered but their exact roles in human
      diseases are still unclear. This review focuses on recent research regarding the
      role of adipokines and new metabolic factors in metabolic derangement or
      cardiovascular disease. 

PMID- 23970881
TI  - Inflammatory cytokine and microRNA responses of primary human dendritic cells
      cultured with Helicobacter pylori strains.
AB  - Primary human dendritic cells (DC) were used to explore the inflammatory
      effectors, including cytokines and microRNAs, regulated by Helicobacter pylori.
      In a 48 h ex-vivo co-culture system, both H. pylori B38 and B45 strains activated
      human DCs and promoted a strong inflammatory response characterized by the early
      production of pro-inflammatory TNFalpha and IL-6 cytokines, followed by IL-10, IL
      1beta, and IL-23 secretion. IL-23 was the only cytokine dependent on the cag
      pathogenicity island status of the bacterial strains. DC activation and cytokine
      production were accompanied by an early miR-146a upregulation followed by a
      strong miR-155 induction, which mainly controlled TNFalpha production. These
      results pave the way for further investigations into the nature of H. pylori
      antigens and the subsequently activated signaling pathways involved in the
      inflammatory response to H. pylori infection, the deregulation of which may
      likely contribute to gastric lymphomagenesis. 

PMID- 23970882
TI  - Erratum: Cooccurrence patterns of plants and soil bacteria in the high-alpine
      subnival zone track environmental harshness.
AB  - [This corrects the article on p. 347 in vol. 3, PMID: 23087675.].

PMID- 23970883
TI  - Non-streptomycete actinomycetes nourish the current microbial antibiotic drug
      discovery.

PMID- 23970884
TI  - NLRP7 and the Genetics of Hydatidiform Moles: Recent Advances and New Challenges.
AB  - NOD-like receptor proteins (NLRPs) are emerging key players in several
      inflammatory pathways in Mammals. The first identified gene coding for a protein
      from this family is Nlrp5 and was originally called Mater for "Maternal Antigen
      That Mouse Embryos Require" for normal development beyond the two-cell stage.
      This important discovery was followed by the identification of other NLRPs
      playing roles in inflammatory disorders and of the first maternal-effect gene in
      humans, NLRP7, which is responsible for an aberrant form of human pregnancy
      called hydatidiform mole (HM). In this review, we recapitulate the various
      aspects of the pathology of HM, highlight recent advances regarding NLRP7 and its
      role in HM and related forms of reproductive losses, and expand our discussion to
      other NLRPs with a special emphasis on those with known roles in mammalian
      reproduction. Our aim is to facilitate the genetic complexity of recurrent fetal
      loss in humans and encourage interdisciplinary collaborations in the fields of
      NLRPs and reproductive loss. 

PMID- 23970886
TI  - Treg inducing adjuvants for therapeutic vaccination against chronic inflammatory
      diseases.
AB  - Many existing therapies in autoimmune diseases are based on systemic suppression
      of inflammation and the observed side effects of these therapies illustrate the
      pressing need for more specific interventions. Regulatory T-cells (Treg) are
      pivotal controllers of (auto-aggressive) immune responses and inflammation, and
      decreased Treg numbers and/or functioning have been associated with autoimmune
      disease. Therefore, Treg became frequently studied targets for more specific
      immunotherapy. Especially antigen-specific targeting of Treg would enable local
      and tailor made interventions, while obviating the negative side effect of
      general immuno-suppression. Self-antigens that participate in inflammation,
      irrespective of the etiology of the different autoimmune diseases, are held to be
      candidate antigens for antigen-specific interventions. Rather than tolerance
      induction to disease inciting self-antigens, which are frequently unknown,
      general self-antigens expressed at sites of inflammation would allow targeting of
      disease independent, but inflammatory-site specific, regulatory mechanisms.
      Preferably, such self-antigens should be abundantly expressed and up-regulated at
      the inflammatory-site. In this perspective heat shock proteins (Hsp) have several
      characteristics that make them highly attractive targets for antigen-specific
      Treg inducing therapy. The development of an antigen-specific Treg inducing
      vaccine is a major novel goal in the field of immunotherapy in autoimmune
      diseases. However, progress is hampered not only by the lack of effective
      antigens, but also by the fact that other factors such as dose, route, and the
      presence or absence of an adjuvant, turned out to be critical unknowns, with
      respect to the effective induction of Treg. In addition, the use of a Treg
      inducing adjuvant might be required to achieve an effective regulatory response,
      in the case of ongoing inflammation. Future goals in clinical trials will be the
      optimization of natural Treg expansion (or the induction of adaptive Treg)
      without loss of their suppressive function or the concomitant induction of non
      regulatory T-cells. Here, we will discuss the potential use of protein/peptide
      based vaccines combined with Treg inducing adjuvants for the development of
      therapeutic vaccines against chronic inflammatory conditions. 

PMID- 23970887
TI  - Divergent genetic mechanisms underlie reversals to radial floral symmetry from
      diverse zygomorphic flowered ancestors.
AB  - Malpighiaceae possess flowers with a unique bilateral symmetry (zygomorphy),
      which is a hypothesized adaptation associated with specialization on neotropical
      oil bee pollinators. Gene expression of two representatives of the CYC2 lineage
      of floral symmetry TCP genes, CYC2A and CYC2B, demarcate the adaxial (dorsal)
      region of the flower in the characteristic zygomorphic flowers of most
      Malpighiaceae. Several clades within the family, however, have independently lost
      their specialized oil bee pollinators and reverted to radial flowers
      (actinomorphy) like their ancestors. Here, we investigate CYC2 expression
      associated with four independent reversals to actinomorphy. We demonstrate that
      these reversals are always associated with alteration of the highly conserved
      CYC2 expression pattern observed in most New World (NW) Malpighiaceae. In NW
      Lasiocarpus and Old World (OW) Microsteria, the expression of CYC2-like genes has
      expanded to include the ventral region of the corolla. Thus, the pattern of gene
      expression in these species has become radialized, which is comparable to what
      has been reported in the radial flowered legume clade Cadia. In striking
      contrast, in NW Psychopterys and OW Sphedamnocarpus, CYC2-like expression is
      entirely absent or at barely detectable levels. This is more similar to the
      pattern of CYC2 expression observed in radial flowered Arabidopsis. These results
      collectively indicate that, regardless of geographic distribution, reversals to
      similar floral phenotypes in this large tropical angiosperm clade have evolved
      via different genetic changes from an otherwise highly conserved developmental
      program. 

PMID- 23970885
TI  - Role of T cell receptor affinity in the efficacy and specificity of adoptive T
      cell therapies.
AB  - Over the last several years, there has been considerable progress in the
      treatment of cancer using gene modified adoptive T cell therapies. Two approaches
      have been used, one involving the introduction of a conventional alphabeta T cell
      receptor (TCR) against a pepMHC cancer antigen, and the second involving
      introduction of a chimeric antigen receptor (CAR) consisting of a single-chain
      antibody as an Fv fragment linked to transmembrane and signaling domains. In this
      review, we focus on one aspect of TCR-mediated adoptive T cell therapies, the
      impact of the affinity of the alphabeta TCR for the pepMHC cancer antigen on both
      efficacy and specificity. We discuss the advantages of higher-affinity TCRs in
      mediating potent activity of CD4 T cells. This is balanced with the potential
      disadvantage of higher-affinity TCRs in mediating greater self-reactivity against
      a wider range of structurally similar antigenic peptides, especially in synergy
      with the CD8 co-receptor. Both TCR affinity and target selection will influence
      potential safety issues. We suggest pre-clinical strategies that might be used to
      examine each TCR for possible on-target and off-target side effects due to self
      reactivities, and to adjust TCR affinities accordingly. 

PMID- 23970888
TI  - Belowground induction by Delia radicum or phytohormones affect aboveground
      herbivore communities on field-grown broccoli.
AB  - Induced plant defence in response to phytophagous insects is a well described
      phenomenon. However, so far little is known about the effect of induced plant
      responses on subsequently colonizing herbivores in the field. Broccoli plants
      were induced in the belowground compartment using (i) infestation by the root
      herbivore Delia radicum, (ii) root application of jasmonic acid (JA) or (iii)
      root application of salicylic acid (SA). The abundance of D. radicum and six
      aboveground herbivores displaying contrasting levels of host specialization were
      surveyed for 5 weeks. Our study showed that the response of herbivores was found
      to differ from one another, depending on the herbivore species, its degree of
      specialization and the root treatment. The abundance of the root herbivore D.
      radicum and particularly the number of emerging adults was decreased by both
      phytohormone treatments, while the number of D. radicum eggs was increased on
      conspecific infested plants. The root infestation exhibited moderate effects on
      the aboveground community. The abundance of the aphid Brevicoryne brassicae was
      strongly increased on D. radicum infested plants, but the other species were not
      impacted. Root hormone applications exhibited a strong effect on the abundance of
      specialist foliar herbivores. A higher number of B. brassicae and Pieris
      brassicae and a lower number of Plutella xylostella were found on JA treated
      plants. On SA treated plants we observed a decrease of the abundance of B.
      brassicae, Pi. rapae, and P. xylostella. Surprisingly, generalist species,
      Mamestra brassicae and Myzus persicae were not affected by root induction
      treatments. Finally, root treatments had no significant effect on either
      glucosinolate (GLS) profiles of the heads or on plant quality parameters. These
      results are discussed from the perspective of below- aboveground interactions and
      adaptations of phytophagous insects to induced plant responses according to their
      trophic specialization level. 

PMID- 23970889
TI  - Pre-breeding for diversification of primary gene pool and genetic enhancement of
      grain legumes.
AB  - The narrow genetic base of cultivars coupled with low utilization of genetic
      resources are the major factors limiting grain legume production and productivity
      globally. Exploitation of new and diverse sources of variation is needed for the
      genetic enhancement of grain legumes. Wild relatives with enhanced levels of
      resistance/tolerance to multiple stresses provide important sources of genetic
      diversity for crop improvement. However, their exploitation for cultivar
      improvement is limited by cross-incompatibility barriers and linkage drags. Pre
      breeding provides a unique opportunity, through the introgression of desirable
      genes from wild germplasm into genetic backgrounds readily used by the breeders
      with minimum linkage drag, to overcome this. Pre-breeding activities using
      promising landraces, wild relatives, and popular cultivars have been initiated at
      International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) to
      develop new gene pools in chickpea, pigeonpea, and groundnut with a high
      frequency of useful genes, wider adaptability, and a broad genetic base. The
      availability of molecular markers will greatly assist in reducing linkage drags
      and increasing the efficiency of introgression in pre-breeding programs. 

PMID- 23970890
TI  - Cytology of the minor-vein phloem in 320 species from the subclass Asteridae
      suggests a high diversity of phloem-loading modes.
AB  - The discovery of abundant plasmodesmata at the bundle sheath/phloem interface in
      Oleaceae (Gamalei, 1974) and Cucurbitaceae (Turgeon et al., 1975) raised the
      questions as to whether these plasmodesmata are functional in phloem loading and
      how widespread symplasmic loading would be. Analysis of over 800 dicot species
      allowed the definition of "open" and "closed" types of the minor vein phloem
      depending on the abundance of plasmodesmata between companion cells and bundle
      sheath (Gamalei, 1989, 1990). These types corresponded to potential symplasmic
      and apoplasmic phloem loaders, respectively; however, this definition covered a
      spectrum of diverse structures of phloem endings. Here, a review of detailed
      cytological analyses of minor veins in 320 species from the subclass Asteridae is
      presented, including data on companion cell types and their combinations which
      have not been reported previously. The percentage of Asteridae species with
      "open" minor vein cytology which also contain sieve-element-companion cell
      complexes with "closed" cytology, i.e., that show specialization for both
      symplasmic and apoplasmic phloem loading, was determined. Along with recent data
      confirming the dissimilar functional specialization of structurally different
      parts of minor vein phloem in the stachyose-translocating species Alonsoa
      meridionalis (Voitsekhovskaja et al., 2009), these findings suggest that
      apoplasmic loading is indispensable in a large group of species previously
      classified as putative symplasmic loaders. Altogether, this study provides formal
      classifications of companion cells and of minor veins, respectively, in 24
      families of the Asteridae based on their structural features, opening the way to
      a close investigation of the relationship between structure and function in
      phloem loading. 

PMID- 23970891
TI  - Microbeam methodologies as powerful tools in manganese hyperaccumulation
      research: present status and future directions.
AB  - Microbeam studies over the past decade have garnered unique insight into
      manganese (Mn) homeostasis in plant species that hyperaccumulate this essential
      mineral micronutrient. Electron- and/or proton-probe methodologies employed to
      examine tissue elemental distributions have proven highly effective in
      illuminating excess foliar Mn disposal strategies, some apparently unique to Mn
      hyperaccumulating plants. When applied to samples prepared with minimal
      artefacts, these are powerful tools for extracting true 'snapshot' data of living
      systems. For a range of reasons, Mn hyperaccumulation is particularly suited to
      in vivo interrogation by this approach. Whilst microbeam investigation of
      metallophytes is well documented, certain methods originally intended for non
      biological samples are now widely applied in biology. This review examines
      current knowledge about Mn hyperaccumulators with reference to microbeam
      methodologies, and discusses implications for future research into metal
      transporters. 

PMID- 23970894
TI  - Retraction: GMO debate: inconclusive.

PMID- 23970893
TI  - A population-based analysis of clustering identifies a strong genetic
      contribution to lethal prostate cancer.
AB  - BACKGROUND: Prostate cancer is a common and often deadly cancer. Decades of study
      have yet to identify genes that explain much familial prostate cancer.
      Traditional linkage analysis of pedigrees has yielded results that are rarely
      validated. We hypothesize that there are rare segregating variants responsible
      for high-risk prostate cancer pedigrees, but recognize that within-pedigree
      heterogeneity is responsible for significant noise that overwhelms signal. Here
      we introduce a method to identify homogeneous subsets of prostate cancer, based
      on cancer characteristics, which show the best evidence for an inherited
      contribution. METHODS: We have modified an existing method, the Genealogical
      Index of Familiality (GIF) used to show evidence for significant familial
      clustering. The modification allows a test for excess familial clustering of a
      subset of prostate cancer cases when compared to all prostate cancer cases.
      RESULTS: Consideration of the familial clustering of eight clinical subsets of
      prostate cancer cases compared to the expected familial clustering of all
      prostate cancer cases identified three subsets of prostate cancer cases with
      evidence for familial clustering significantly in excess of expected. These
      subsets include prostate cancer cases diagnosed before age 50 years, prostate
      cancer cases with body mass index (BMI) greater than or equal to 30, and prostate
      cancer cases for whom prostate cancer contributed to death. CONCLUSIONS: This
      analysis identified several subsets of prostate cancer cases that cluster
      significantly more than expected when compared to all prostate cancer familial
      clustering. A focus on high-risk prostate cancer cases or pedigrees with these
      characteristics will reduce noise and could allow identification of the rare
      predisposition genes or variants responsible.

PMID- 23970892
TI  - Flower color as a model system for studies of plant evo-devo.
AB  - Even though pigmentation traits have had substantial impacts on the field of
      animal evolutionary developmental biology, they have played only relatively minor
      roles in plant evo-devo. This is surprising given the often direct connection
      between flower color and fitness variation mediated through the effects of
      pollinators. At the same time, ecological and evolutionary genetic studies have
      utilized the molecular resources available for the anthocyanin pathway to
      generate several examples of the molecular basis of putatively adaptive
      transitions in flower color. Despite this opportunity to synthesize experimental
      approaches in ecology, evolution, and developmental biology, the investigation of
      many fundamental questions in evo-devo using this powerful model is only at its
      earliest stages. For example, a long-standing question is whether predictable
      genetic changes accompany the repeated evolution of a trait. Due to the conserved
      nature of the biochemical and regulatory control of anthocyanin biosynthesis, it
      has become possible to determine whether, and under what circumstances, different
      types of mutations responsible for flower color variation are preferentially
      targeted by natural selection. In addition, because plants use anthocyanin and
      related compounds in vegetative tissue for other important physiological
      functions, the identification of naturally occurring transitions from unpigmented
      to pigmented flowers provides the opportunity to examine the mechanisms by which
      regulatory networks are co-opted into new developmental domains. Here, we review
      what is known about the ecological and molecular basis of anthocyanic flower
      color transitions in natural systems, focusing on the evolutionary and
      developmental features involved. In doing so, we provide suggestions for future
      work on this trait and suggest that there is still much to be learned from the
      evolutionary development of flower color transitions in nature. 

PMID- 23970895
TI  - SIVIC: Open-Source, Standards-Based Software for DICOM MR Spectroscopy Workflows.
AB  - Quantitative analysis of magnetic resonance spectroscopic imaging (MRSI) data
      provides maps of metabolic parameters that show promise for improving medical
      diagnosis and therapeutic monitoring. While anatomical images are routinely
      reconstructed on the scanner, formatted using the DICOM standard, and interpreted
      using PACS workstations, this is not the case for MRSI data. The evaluation of
      MRSI data is made more complex because files are typically encoded with vendor
      specific file formats and there is a lack of standardized tools for
      reconstruction, processing, and visualization. SIVIC is a flexible open-source
      software framework and application suite that enables a complete scanner-to-PACS
      workflow for evaluation and interpretation of MRSI data. It supports conversion
      of vendor-specific formats into the DICOM MR spectroscopy (MRS) standard,
      provides modular and extensible reconstruction and analysis pipelines, and
      provides tools to support the unique visualization requirements associated with
      such data. Workflows are presented which demonstrate the routine use of SIVIC to
      support the acquisition, analysis, and delivery to PACS of clinical (1)H MRSI
      datasets at UCSF. 

PMID- 23970896
TI  - Quality of life in alopecia areata: a sample of tunisian patients.
AB  - Background. Alopecia areata (AA) has a significant impact on the quality of life
      and social interaction of those suffering from it. Our aim was to assess the
      impact of AA on the quality of life. Methods. Fifty patients diagnosed with AA
      seen in the Department of Dermatology of Hedi Chaker University Hospital, between
      March 2010 and July 2010, were included. Quality of life was measured by SF 36;
      severity of AA was measured by SALT. Results. Eighty percent had patchy alopecia
      with less than 50% involvement, 12% had patchy alopecia with 50-99% involvement,
      and 8% had alopecia totalis. Compared with the general population, AA patients
      presented a significantly altered quality of life, found in the global score and
      in five subscores of the SF-36: mental health, role emotional, social
      functioning, vitality, and general health. Gender, age, marital status, and
      severity of alopecia areata had a significant influence on patients' quality of
      life. Conclusions. This study indicates that patients with AA experience a poor
      quality of life, which impacts their overall health. We suggest screening for
      psychiatric distress. Studies of interventions such as counseling,
      psychoeducation, and psychotherapeutic interventions to reduce the impact of the
      disease may be warranted. 

PMID- 23970898
TI  - Gut microbiota, microinflammation, metabolic profile, and zonulin concentration
      in obese and normal weight subjects.
AB  - The association between gut microbiota and circulating zonulin level, a marker of
      intestinal permeability, has not been studied yet. The aim of the study is the
      assessment of plasma zonulin, haptoglobin and proinflammatory cytokines (TNF-
      alpha and IL-6) levels in relation to composition of gut microbiota in obese and
      normal weight subjects. Circulating inflammation markers, such as TNF- alpha ,
      sTNFR1, sTNFR2, IL-6, zonulin, and haptoglobin levels were measured and
      semiquantitative analysis of gut microbiota composition was carried out in 50
      obese and 30 normal weight subjects without concomitant diseases. Higher
      circulating zonulin, TNF- alpha , sTNFR1, sTNFR2, and IL-6 levels were found in
      the obese subjects. Plasma zonulin level correlated positively with age (r =
      0.43, P < 0.001), body mass (r = 0.30, P < 0.01), BMI (r = 0.33, P < 0.01), fat
      mass and fat percentage (r = 0.31, P < 0.01 and r = 0.23, P < 0.05, resp.).
      Positive correlations between bacterial colony count and sTNFR1 (r = 0.33, P <
      0.01) and plasma zonulin (r = 0.26, P < 0.05) but not haptoglobin levels were
      found. Additionally, plasma zonulin level was proportional to daily energy intake
      (r = 0.27, P < 0.05) and serum glucose concentration (r = 0.18, P < 0.05) and
      inversely proportional to diet protein percentage (r = -0.23, P < 0.05). Gut
      microbiota-related systemic microinflammation in the obese is reflected by
      circulating zonulin level, a potential marker of interstitial permeability. 

PMID- 23970897
TI  - Metabolic and clinical consequences of hyperthyroidism on bone density.
AB  - In 1891, Von Recklinghausen first established the association between the
      development of osteoporosis in the presence of overt hyperthyroidism. Subsequent
      reports have demonstrated that BMD loss is common in frank hyperthyroidism, and,
      to a lesser extent, in subclinical presentations. With the introduction of
      antithyroid medication in the 1940s to control biochemical hyperthyroidism, the
      accompanying bone disease became less clinically apparent as hyperthyroidism was
      more successfully treated medically. Consequently, the impact of the above normal
      thyroid hormones in the pathogenesis of osteoporosis may be presently
      underrecognized due to the widespread effective treatments. This review aims to
      present the current knowledge of the consequences of hyperthyroidism on bone
      metabolism. The vast number of recent papers touching on this topic highlights
      the recognized impact of this common medical condition on bone health. Our focus
      in this review was to search for answers to the following questions. What is the
      mechanisms of action of thyroid hormones on bone metabolism? What are the
      clinical consequences of hyperthyroidism on BMD and fracture risk? What
      differences are there between men and women with thyroid disease and how does
      menopause change the clinical outcomes? Lastly, we report how different
      treatments for hyperthyroidism benefit thyroid hormone-induced osteoporosis. 

PMID- 23970899
TI  - Cellular response to a novel fetal acellular collagen matrix: implications for
      tissue regeneration.
AB  - Introduction. PriMatrix (TEI Biosciences Inc., Boston, MA, USA) is a novel
      acellular collagen matrix derived from fetal bovine dermis that is designed for
      use in partial- and full-thickness wounds. This study analyzes the cellular
      response to PriMatrix in vivo, as well as the ability of this matrix to
      facilitate normal tissue regeneration. Methods. Five by five mm squares of
      rehydrated PriMatrix were implanted in a subcutaneous fashion on the dorsum of
      wild-type mice. Implant site tissue was harvested for histology,
      immunohistochemistry (IHC), and flow cytometric analyses at multiple time points
      until day 28. Results. PriMatrix implants were found to go through a biological
      progression initiated by a transient infiltrate of inflammatory cells, followed
      by mesenchymal cell recruitment and vascular development. IHC analysis revealed
      that the majority of the implanted fetal dermal collagen fibers persisted through
      day 28 but underwent remodeling and cellular repopulation to form tissue with a
      density and morphology consistent with healthy dermis. Conclusions. PriMatrix
      implants undergo progressive in vivo remodeling, facilitating the regeneration of
      histologically normal tissue through a mild inflammatory and progenitor cell
      response. Regeneration of normal tissue is especially important in a wound
      environment, and these findings warrant further investigation of PriMatrix in
      this setting. 

PMID- 23970900
TI  - Limb body wall complex with sacrococcygeal mass and agenesis of external
      genitalia.
AB  - Limb body wall complex (LBWC) is a rare clinicopathological entity, characterized
      by the presence of an abdominal wall defect associated with variable spectrum of
      limb and visceral anomalies. A stillborn baby of LBWC with placentoabdominal
      phenotype is reported here. Kyphoscoliosis, sacrococcygeal mass and agenesis of
      external genitalia are the associated features. 

PMID- 23970901
TI  - Acute Glomerulonephritis in a Child with Chlamydia pneumoniae Infection: A Case
      Report.
AB  - Background. Infectious diseases seem to be an important and independent risk
      factor for renal failure, but the underlying mechanism of renal involvement
      during some kinds of infectious diseases is still unclear, even if the literature
      data report immunomediated and/or autoimmune mechanisms to explain the pathogenic
      relationship between the two diseases. In paediatric patients, Chlamydia
      pneumoniae is a rare cause of renal complications and it may manifest in several
      ways, mainly involving the respiratory system, even if also renal and glomerulalr
      complications, have been described. Case Diagnosis/Treatment. Herein we report a
      case of a 3-year-old child who developed an acute glomerulonephritis that was
      chronologically, clinically, and biologically related to a previous Chlamydia
      pneumoniae infection. On our knowledge, in the literature it is the youngest
      patient with renal involvement during course of Chlamydia pneumoniae infection
      ever reported. Conclusions. The present case supports the hypothesis of a rather
      close causal relationship between this infective agent and renal and glomerular
      symptoms occurred in this child, during an acute episode of respiratory disease. 

PMID- 23970902
TI  - An atypical case of taravana syndrome in a breath-hold underwater fishing
      champion: a case report.
AB  - Dysbaric accidents are usually referred to compressed air-supplied diving.
      Nonetheless, some cases of decompression illness are known to have occurred among
      breath-hold (BH) divers also, and they are reported in the medical literature. A
      male BH diver (57 years old), underwater fishing champion, presented neurological
      disorders as dizziness, sensory numbness, blurred vision, and left frontoparietal
      pain after many dives to a 30-35 meters sea water depth with short surface
      intervals. Symptoms spontaneously regressed and the patient came back home. The
      following morning, pain and neurological impairment occurred again and the diver
      went by himself to the hospital where he had a generalized tonic-clonic seizure
      and lost consciousness. A magnetic resonance imaging of the brain disclofsed a
      cortical T1-weighted hypointense area in the temporal region corresponding to
      infarction with partial hemorrhage. An early hyperbaric oxygen therapy led to
      prompt resolution of neurological findings. All clinical and imaging
      characteristics were referable to the Taravana diving syndrome, induced by
      repetitive prolonged deep BH dives. The reappearance of neurological signs after
      an uncommon 21-hour symptom-free interval may suggest an atypical case of
      Taravana syndrome. 

PMID- 23970903
TI  - An evaluation of a novel mask in four patients with obstructive sleep apnea and
      overlap syndromes.
AB  - We present four cases of adults with obstructive sleep apnea in whom positive
      airway pressure therapy alone failed to provide adequate oxygenation. We have
      previously reported the use of dual mask for ventilatory support of a patient
      postoperatively (Porhomayon et al., 2013). Here, we report an evaluation of the
      dual mask in four patients with overlap syndromes. Application of dual mask
      provided adequate oxygenation with lower continuous positive airway pressure
      (CPAP)/bilevel positive airway pressure (BIPAP) pressure levels. 

PMID- 23970904
TI  - Antigenic Peptides Capable of Inducing Specific Antibodies for Detection of the
      Major Alterations Found in Type 2B Von Willebrand Disease.
AB  - Von Willebrand disease (VWD) is an inherited hemorrhagic disorder promoted by
      either quantitative or qualitative defects of the von Willebrand factor (VWF).
      The disease represents the most common human coagulopathy afflicting 1.3% of the
      population. Qualitative defects are subdivided into four subtypes and classified
      according to the molecular dysfunction of the VWF. The differential diagnosis of
      the VWD is a difficult task, relying on a panel of tests aimed to assess the
      plasma levels and function of the VWF. Here, we propose biochemical approaches
      for the identification of structural variants of the VWF. A bioinformatic
      analysis was conducted to design seven peptides among which three were
      representatives of specific amino acid sequences belonging to normal VWF and four
      encompassed sequences found in the most common VWD subtype 2B. These peptides
      were used to immunize mice, after which, peptide-specific immunoglobulins were
      purified. This resulted in four Ig preparations capable of detecting alterations
      in the subtype 2B VWD plus additional three antibody fractions targeting the
      normal VWF. The panel of antibodies could serve many applications among them (1)
      assessment of VWF: antigen interaction, (2) VWF multimer analysis, and (3)
      production of monoclonal antibodies against VWF for therapeutic purposes as in
      thrombotic thrombocytopenic purpura. 

PMID- 23970907
TI  - The importance of early intervention with children and youth in the autism
      spectrum.

PMID- 23970906
TI  - Personality disorders begin in adolescence.

PMID- 23970905
TI  - Obesity and asthma: physiological perspective.
AB  - Obesity induces some pertinent physiological changes which are conducive to
      either development of asthma or cause of poorly controlled asthma state. Obesity
      related mechanical stress forces induced by abdominal and thoracic fat generate
      stiffening of the lungs and diaphragmatic movements to result in reduction of
      resting lung volumes such as functional residual capacity (FRC). Reduced FRC is
      primarily an outcome of decreased expiratory reserve volume, which pushes the
      tidal breathing more towards smaller high resistance airways, and consequentially
      results in expiratory flow limitation during normal breathing in obesity. Reduced
      FRC also induces plastic alteration in the small collapsible airways, which may
      generate smooth muscle contraction resulting in increased small airway
      resistance, which, however, is not picked up by spirometric lung volumes. There
      is also a possibility that chronically reduced FRC may generate permanent
      adaptation in the very small airways; therefore, the airway calibres may not
      change despite weight reduction. Obesity may also induce bronchodilator
      reversibility and diurnal lung functional variability. Obesity is also associated
      with airway hyperresponsiveness; however, the mechanism of this is not clear.
      Thus, obesity has effects on lung function that can generate respiratory distress
      similar to asthma and may also exaggerate the effects of preexisting asthma. 

PMID- 23970908
TI  - The joint hierarchical structure of adolescent personality pathology: converging
      evidence from two approaches to measurement.
AB  - OBJECTIVE: To examine the joint hierarchical structure of two measures of
      adolescent personality pathology within a community sample of Canadian
      adolescents. METHOD: Self-reported data on demographic information and
      pathological personality traits were obtained from 144 youth (M age = 16.08
      years, SD = 1.30). Personality pathology was measured using the youth-version of
      the Schedule for Nonadaptive and Adaptive Personality (SNAP-Y; Linde, Stringer,
      Simms, & Clark, in press) and the Dimensional Personality Symptom Item Pool
      (DIPSI; De Clercq, De Fruyt, Van Leeuwen, & Mervielde, 2006). Lower-order scales
      were subjected to structural hierarchical analyses. RESULTS: Scales from the two
      measures were complementary in defining higher-order traits. Traits at the 4
      factor level of the hierarchy (Need for Approval, Disagreeableness, Detachment,
      and Compulsivity) showed similarities and differences with previous results in
      adults. CONCLUSIONS: The current investigation integrated top-down and bottom-up
      measures for a comprehensive account of the higher-order hierarchy of adolescent
      personality pathology. Results are discussed in the context of convergence across
      approaches and in comparison with previous findings in adult samples.

PMID- 23970909
TI  - Reliability and validity of borderline personality disorder in hospitalized
      adolescents.
AB  - OBJECTIVE: Although the DSM-IV suggests that dysfunctional personality patterns
      can be traced back to adolescence, there is continued debate about whether
      borderline personality disorder (BPD) can be reliably and validly diagnosed
      before age 18. The current study examined the reliability and validity of BPD in
      a large sample of adolescent psychiatric patients. METHOD: BPD and Axis I
      disorders were assessed with validated structured interviews and a series of
      clinical, emotion, and personality correlates were assessed with validated self
      report questionnaires. RESULTS: Consistent with previous studies in adolescent
      clinical samples, approximately 30% of patients in the current sample met
      criteria for BPD. The nine BPD criteria demonstrated good internal consistency,
      equivalent to rates reported in adult samples. In addition, BPD was related to
      greater clinical severity and impairment as indexed by strong associations with
      all major Axis I disorders, as well as with dimensional measures of depression,
      anxiety, difficulties with emotion regulation, and impulsiveness. Notably,
      reliability and validity remained satisfactory even when analyses were limited to
      younger adolescents between the ages of 12 and 14. CONCLUSIONS: Overall, findings
      suggest that BPD can be reliably and validly diagnosed in adolescents as young as
      12-14 years old.

PMID- 23970910
TI  - The Neurobiological Basis of Adolescent-onset Borderline Personality Disorder.
AB  - OBJECTIVE: Over the past two decades, neurobiological studies in adult onset
      borderline personality disorder have made important strides, but inquiry into
      adolescent-onset BPD is still in its infancy and our understanding of the
      neurobiology of adolescent BPD remains highly tentative. METHODS: This paper
      highlights recent findings in genetics, neuroendocrinology and neuroimaging for
      adult and adolescent-onset BPD. RESULTS: Neurobiological studies of adolescent
      onset BPD to date have focused mainly on volumetric studies of various brain
      regions and measurements of HPA axis components, with comparatively few
      publications on brain functioning. CONCLUSION: Such information is essential to
      developing more effective screening, treatment and preventive strategies.

PMID- 23970911
TI  - Temperament and Maltreatment in the Emergence of Borderline and Antisocial
      Personality Pathology during Early Adolescence.
AB  - OBJECTIVE: The present study utilized a prospective, longitudinal design to
      examine the role of temperament and maltreatment in predicting the emergence of
      borderline (BPD) and antisocial (ASPD) personality disorder symptoms during
      adolescence. METHOD: Two hundred and forty-five children aged between 11 and 13
      years were recruited from primary schools in Melbourne, Australia. Participants
      completed temperament, maltreatment, BPD and ASPD symptom measures, and
      approximately two years later, 206 participants were again assessed for BPD and
      ASPD symptoms. RESULTS: The findings indicate that childhood neglect is a
      significant predictor of an increase in BPD symptoms, while childhood abuse is a
      significant predictor of an increase in ASPD symptoms. Moreover, abuse and
      neglect acted as moderators of the relationship between temperament dimensions
      and increase in BPD and ASPD symptoms, respectively. Abuse was associated with an
      increase in BPD symptoms for children with low Affiliation, while neglect was
      associated with an increase in ASPD symptoms for children with low Effortful
      Control. CONCLUSIONS: The current study contributes much needed prospective,
      longitudinal information on the early development of symptoms of BPD and ASPD,
      and supports importance of both temperamental and environmental factors in
      predicting the emergence of these mental health problems early in life.

PMID- 23970913
TI  - Nocturnal Anxiety in a Youth with Rapid-onset Obesity, Hypothalamic Dysfunction,
      Hypoventilation, and Autonomic Dysregulation (ROHHAD).
AB  - OBJECTIVE: Behavioral and psychiatric disorders are common in youth with rapid
      onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic
      dysregulation (ROHHAD). We outline a rational approach to psychiatric treatment
      of a patient with a complex medical condition. METHODS: We report the course of
      symptoms in a teen with ROHHAD, the inpatient treatment, and review current
      evidence for use of psychopharmacologic agents in youth with sleep and anxiety
      disturbances. RESULTS: A 14-year-old female began rapidly gaining weight as a
      preschooler, developed hormonal imbalance, and mixed sleep apnea. Consultation
      was requested after a month of ROHHAD exacerbation, with severe anxiety,
      insomnia, and auditory hallucinations. Olanzapine and citalopram were helpful in
      controlling the symptoms. Following discharge, the patient gained weight and
      olanzapine was discontinued. Lorazepam was started in coordination with pulmonary
      service. Relevant pharmacologic considerations included risk of respiratory
      suppression, history of paradoxical reaction to hypnotics, hepatic isoenzyme
      interactions and side effects of antipsychotics. CONCLUSIONS: Core symptoms of
      ROHHAD may precipitate psychiatric disorders. A systematic evidence-based
      approach to psychopharmacology is necessary in the setting of psychiatric
      consultation.

PMID- 23970912
TI  - Treatment of borderline personality disorder in youth.
AB  - OBJECTIVES: Borderline personality disorder (BPD) is frequently encountered in
      both adult and youth populations. There is a robust literature supporting
      psychotherapy for adults with BPD, but the literature supporting its use for BPD
      in youth is more limited. METHODS: A literature review was conducted using the
      keywords "borderline personality disorders" and "adolescence." Relevant articles
      were reviewed for inclusion. RESULTS: Several specialized treatments have been
      studied with mixed results. Dialectical behaviour therapy has no randomized
      controlled trials in adolescents, emotion regulation training has not
      demonstrated superiority of treatment as usual, and cognitive analytic therapy
      has demonstrated more rapid recovery but little difference at follow-up.
      Mentalization-based treatment has one study supporting its use in self-harming
      adolescents. Pharmacotherapy has no evidence supporting its use in this
      population. CONCLUSIONS: Structured therapy may be the most important therapeutic
      component in this population.

PMID- 23970914
TI  - Commentary: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation,
      and Autonomic Dysregulation (ROHHAD): Remember Your ABCs (Airway, Breathing,
      Circulation).

PMID- 23970915
TI  - Outside the Black Box: Re-assessing Pediatric Antidepressant Prescription.
AB  - OBJECTIVE: The purpose of this review is to assess whether evidence supports a
      favorable risk/benefit profile for pediatric antidepressant use and
      reconsideration of the black box. METHOD: The review examines studies post-black
      box purporting to show declines in pediatric antidepressant use and rising youth
      suicide, summarizes evidence for efficacy and safety of pediatric
      antidepressants, and discusses irregularities in recent meta-analyses of
      fluoxetine for youth. RESULTS: Pediatric antidepressant prescription did not
      significantly decline post-black box and youth suicide has risen only in recent
      years. Recent meta-analyses fail to undermine evidence that antidepressants are
      associated with increased risk of suicidality in youth. CONCLUSIONS: First line
      prescription of antidepressants for youth is not advisable. The black box and
      international warnings on pediatric use of antidepressants are warranted. Wider
      availability of psychosocial options for depressed youth is recommended.

PMID- 23970916
TI  - The correlation between educational levels and central obesity in the north of
      Iran: An epidemiologic study.
AB  - BACKGROUND: The main aim of this study was to evaluate the association between
      educational levels and central obesity in northern Iran in 2010. METHODS: This
      was a cross-sectional study carried out on 2428 subjects (1227 men and 1201
      women) of 15-65 years of age who were chosen by cluster and stratified sampling
      methods. Subjects were randomly selected from 125 clusters and each cluster
      included 20 cases. Interviewers recorded the data using a multidimensional
      questionnaire comprising socio-demographic indexes. RESULTS: Central obesity was
      seen in 34.8% of all subjects (15.9% male and 56.7% female) and in 15% of
      uneducated people. In the uneducated group, it was 20.0% and 31.1% higher than in
      the 1-9 years of schooling and high school or college educated groups,
      respectively (P = 0.001). The risk of central obesity increased in uneducated
      people (OR = 4.214, P = 0.001) and in people with 1-9 years of schooling (OR =
      2.283, P = 0.001) compared with high school or college educated people. The risk
      of central obesity was higher in urban areas than in rural area (OR = 1.481, P =
      0.001), in women than men (OR = 7.039, P = 0.001), in 40-65 year olds than 15-40
      year olds (OR = 3.090, P = 0.001), and in the wealthy economic group than poor
      economic group (OR = 1.360, P = 0.013). The risk of central obesity increased in
      urban areas (OR = 2.266, P = 0.001) and the wealthy economic group (OR = 1.732, P
      = 0.001) after it was adjusted for education. CONCLUSION: Central obesity as a
      health problem in northern Iran has been supported in this study, and it had an
      inverse correlation with educational levels. Public health programs that aim to
      reduce central obesity should mainly focus on the illiterate and low educated
      people.

PMID- 23970917
TI  - Effects of quince leaf extract on biochemical markers and coronary
      histopathological changes in rabbits.
AB  - BACKGROUND: Atherosclerosis is the main cause of cardiovascular disease which is
      caused by a high-fat diet. Many of these patients use boiled quince leaves for
      their treatment. However, the supporting scientific information is limit. The aim
      of this study was to evaluate the effect of quince leaf on the progression of
      atherosclerosis and whether it can be an appropriate alternative to statins.
      METHODS: 24 male rabbits were randomly divided into two groups: normal diet (6 n)
      and high-cholesterol diet (2% cholesterol, 18 n) for 8 weeks. At the end of the 8
      weeks, both groups underwent blood sampling and their biochemical markers were
      measured. Then, all animals in the normal-diet group and three of the high
      cholesterol diet group were killed to investigate atheromic plaque in their
      coronary artery. The 15 remaining rabbits of the high-cholesterol diet group were
      randomly divided into 3 groups (5 n) after discontinuation of the fatty diet. The
      first group was not given any treatment, the second received atorvastatin (0.5
      mg/kg) orally, and the third received quince leaf extract (50 mg/kg) orally for
      12 weeks. At the end of this period, after blood sampling, biopsy of coronary
      artery was performed for histological study. RESULTS: The results showed that
      atorvastatin and quince leaf significantly decreased total cholesterol,
      triglyceride, LDL, AST, ALT, AP, BUN, and Cr levels compared with the first group
      of the high-cholesterol diet group (P < 0.05). No significant difference was
      found between atorvastatin and quince leaf extract groups in biochemical markers
      and atherosclerotic plaque in coronary artery. CONCLUSION: Atorvastatin and
      quince leaf extract can effectively prevent the progression of atherosclerosis in
      coronary arteries. According to the results of this study and also lower toxic
      effects of herbal medication compared to synthetic medication, leaf extract can
      be a substitute for statins in treatment and prevention of cardiovascular
      disease. The anti-atherosclerotic effect of quince leaf is most likely related to
      its antioxidant components.

PMID- 23970918
TI  - Developing an appropriate model for self-care of hypertensive patients: first
      experience from EMRO.
AB  - BACKGROUND: Cardiovascular diseases (CVDs) constitute 53% of deaths above the age
      of 30; 54% of these deaths are attributed to high blood pressure. Coronary artery
      disease (CAD) is the main cause of mortality in the world. Hypertension accounts
      for 13% of mortalities and 6% of morbidities and is one of the main risk factors
      that cause loss of healthy life years. Blood pressure is not optimally controlled
      even among those who are aware of their disease. Previous studies showed that
      apart from pharmacological treatment, lifestyle improvement can also play a
      significant role in the prevention of high blood pressure CVDs. Self-care among
      them has been addressed in several previous studies. There are few self-care
      programs in Iran, but no study has been conducted on blood pressure. METHODS: In
      this study the primary model is designed and then revised, and in the pilot study
      the feasibility of the project was approved and the final model presented.
      RESULTS: The current project proposes a model for self-care of hypertensive
      patients and their families, and is based on education of health care providers
      and patients in such a way that patients can control their illness. CONCLUSION:
      The model can be implemented at a national scale.

PMID- 23970919
TI  - Factors affecting outcome of primary percutaneous coronary intervention for acute
      myocardial infarction.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PCI) is the main
      treatment for patients with ST-segment elevation myocardial infarction (STEMI).
      We investigated factors affecting the major complications of this procedure.
      METHODS: This case-control study assessed 200 patients receiving primary PCI for
      STEMI. Effects of some factors including age, sex, coronary artery risk factors,
      left ventricular function, thrombolysis in myocardial infarction (TIMI) flow, and
      number of involved vessels on major adverse cardiac events (MACE) were studied.
      RESULTS: Two thirds of patients were male but sex had no significant effect on
      MACE. Similarly, age, hypertension, and hyperlipidemia did not significantly
      affect the incidence of MACE. However, Killip class, left ventricular ejection
      fraction, diabetes, TIMI flow, and type of involved vessels had significant
      relations with the incidence of MACE. CONCLUSION: According to our findings,
      factors such as diabetes, left ventricular function, left anterior descending
      artery involvement, and low TIMI flow are risk factors of MACE.

PMID- 23970920
TI  - The relationship between inflammatory markers, angiogenesis, and obesity.
AB  - Obesity is recognized as a chronic low grade and systemic inflammatory disease.
      Angiogenesis is critical for adipose tissue expansion. Several evidences have
      demonstrated that angiogenesis sustains inflammation by preparing oxygen and
      nutrients for inflammatory cells and inflammation in turn can cause insulin
      resistance, type 2 diabetes, and cardiovascular disease. The understanding of
      mechanisms of obesity especially main roles of inflammation and angiogenesis in
      fat mass expansion can lead to therapeutic approaches in growing field of obesity
      and its related disorders. In this review, we studied the relationship between
      obesity, angiogenesis, and inflammation. 

PMID- 23970921
TI  - A case report of truncus arteriosus communis and genetic counseling.
AB  - BACKGROUND: Truncus arteriosus communis (TAC) is a rare heart disorder with the
      prevalence of approximately 1%, mostly in male newborns. In this disease, aorta
      and pulmonary artery have not been separated during fetus development and both
      originate jointly from left ventricle. In addition, various disorders are
      reported like ventricular septal defect (VSD), mitral and tricuspid valves
      defects, aortic septal defect (ASD), reduction of lung and lung vessels'
      resistance, pulmonary hypertension, increase in heart rate, high perspiration,
      bad digestion, and tetralogy of Fallot. CASR REPORT: Parents of deceased patient
      were referred for genetic counseling after the death of third girl due to severe
      cardiac disorder. Cardiologist declared the disease in deceased girl as TAC based
      on findings along with VSD, ASD and hypoplastic aortic arch which resulted to
      death in the first day of birth. CONCLUSION: There was no chromosomal disorder in
      chromosome analysis of patient' skin. Parents were interested to have another
      child, so they were referred to university's Genetic Counseling Center to become
      aware of their next child's condition. This disorder is genetically heterogeneous
      and multifactorial and because all external factors are not recognized, the
      accurate estimation of risk is not possible and the probability of risk for the
      next child is about 10% to 20%.

PMID- 23970922
TI  - Global coronary arteries spasm in a young patient.
AB  - BACKGROUND: Coronary artery spasm is a transient narrowing of coronary arteries
      that slows or stops blood flow through the artery. CASE REPORT: We present a 42
      year-smoker man without any medical problem who developed syncope. Coronary
      angiography revealed diffuse significant narrowing of proximal left anterior
      descending artery (LAD), 90% osteal stenosis of large obtuse marginal (OM), 90%
      diffuse narrowing of proximal right coronary artery (RCA), which was relieved by
      intracoronary administration of nitrate. He was discharged on calcium channel
      blockers and nitrates but one month later developed syncope again and died.
      CONCLUSION: Multivessel coronary artery spasm should be considered in young
      smoker patients without any other coronary risk factors who present with syncope.

PMID- 23970923
TI  - The correlation between early complications of percutaneous coronary intervention
      and high sensitive C-reactive protein.
AB  - BACKGROUND: Increased incidence of cardiovascular diseases, especially coronary
      artery disease (CAD), during recent decades shows this disease entity to be the
      leading cause of death in the world. On the other hand many successes were
      achieved in the treatment of these diseases with new technology, which has its
      own side effects and threats for the patient. Among these new strategies is
      percutaneous coronary intervention (PCI), especially with stent implantation.
      Although coronary stents are effective in the treatment of dissection and
      prevention of restenosis, many side effects and even death have been observed,
      from 5-10% per year. Some studies showed that there is a relation between high
      sensitivity C-reactive protein (hs-CRP), as a laboratory marker for early
      detection of thrombosis and/or restenosis, and early complications of
      percutaneous coronary intervention. The aim of this study is to evaluate hs-CRP
      level in patients after PCI and to investigate if this can be a prognostic value
      for detection of early complication. METHODS: This is a descriptive, analytical
      study done in Shahid Chamran Hospital (Isfahan, Iran) in 2011-2012. 87 patients
      who had undergone PCI were studied. Their hs-CRP level was measured before and
      after the study. Moreover, early stent complications were detected during the
      first 24 hours after insertion. The data was recorded in a researcher-constructed
      checklist and analyzed by SPSS for Windows 20. RESULTS: The mean +/- SD of hs-CRP
      level in patients with and without complication were 1.36 +/- 0.97 and 3.09 +/-
      1.8, respectively. According to Student's t-test, the hs-CRP level in patients
      with early complications was higher than patients without early complications of
      stent implantation; the difference was statistically significant (P < 0.001).
      CONCLUSION: The hs-CRP serum concentrations of patients with, and without early
      stent complications were significantly different. According to the control
      diseases center (CDC) guideline, patients with a high level of hs-CRP need
      special care and attention.

PMID- 23970924
TI  - Homeostatic T cell proliferation after islet transplantation.
AB  - Pancreatic islet transplantation in patients with type 1 diabetes mellitus is
      performed under immunosuppression to avoid alloreactive T cell responses and to
      control the reactivation of autoreactive memory T cells. However, lymphopenia
      associated with immunosuppression and T cell depletion can induce a paradoxical
      expansion of lymphocyte subsets under the influence of homeostatic proliferation.
      Homeostatic T cell proliferation is mainly driven by the IL-7/IL-7 receptor axis,
      a molecular pathway which is not affected by standard immune-suppressive drugs
      and, consequently, represents a novel potential target for immuno-modulatory
      strategies. In this review, we will discuss how homeostatic T cell proliferation
      can support autoimmunity recurrence after islet transplantation and how it can be
      targeted by new therapeutic approaches. 

PMID- 23970925
TI  - TSE diagnostics: recent advances in immunoassaying prions.
AB  - Transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of
      rare fatal neurodegenerative diseases, affecting humans and animals. They are
      believed to be the consequence of the conversion of the cellular prion protein to
      its aggregation-prone, beta -sheet-rich isoform, named prion. Definite diagnosis
      of TSEs is determined post mortem. For this purpose, immunoassays for analyzing
      brain tissue have been developed. However, the ultimate goal of TSE diagnostics
      is an ante mortem test, which would be sensitive enough to detect prions in body
      fluids, that is, in blood, cerebrospinal fluid, or urine. Such a test would be of
      paramount importance also for screening of asymptomatic carriers of the disease
      with the aim of increasing food, drugs, and blood-derived products safety. In the
      present paper, we have reviewed recent advances in the development of
      immunoassays for the detection of prions. 

PMID- 23970927
TI  - Antiangiogenic activity and pharmacogenomics of medicinal plants from traditional
      korean medicine.
AB  - Aim. In the present study, we investigated the antiangiogenic properties of 59
      plants used in traditional Korean medicine. Selected phytochemicals were
      investigated in more detail for their modes of action. Methods. A modified
      chicken-chorioallantoic-membrane (CAM) assay using quail eggs was applied to test
      for antiangiogenic effects of plant extracts. A molecular docking in silico
      approached the binding of plant constituents to the vascular endothelial growth
      factor receptors 1 and 2 (VEGFR1, VEGFR2). Microarray-based mRNA expression
      profiling was employed to correlate the 50% inhibition concentrations (IC50) of a
      panel of 60 NCI cell lines to these phytochemicals. Results. Extracts from Acer
      mono leaves, Reynoutria sachalniensis fruits, Cinnamomum japonicum stems, Eurya
      japonica leaves, Adenophora racemosa whole plant, Caryopteris incana leaves
      stems, and Schisandra chinensis stems inhibited angiogenesis more than 50% in
      quail eggs. Selected phytochemicals from Korean plants were analyzed in more
      detail using microarray-based mRNA expression profiles and molecular docking to
      VEGFR1 and VEGFR2. These results indicate multifactorial modes of action of these
      natural products. Conclusion. The antiangiogenic activity of plants used in
      traditional Korean medicine implicates their possible application for diseases
      where inhibition of blood vessel formation is desired, for example, cancer,
      macular degeneration, diabetic retinopathy and others. 

PMID- 23970926
TI  - The role of the innate immune system in Alzheimer's disease and frontotemporal
      lobar degeneration: an eye on microglia.
AB  - In the last few years, genetic and biomolecular mechanisms at the basis of
      Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) have been
      unraveled. A key role is played by microglia, which represent the immune effector
      cells in the central nervous system (CNS). They are extremely sensitive to the
      environmental changes in the brain and are activated in response to several
      pathologic events within the CNS, including altered neuronal function, infection,
      injury, and inflammation. While short-term microglial activity has generally a
      neuroprotective role, chronic activation has been implicated in the pathogenesis
      of neurodegenerative disorders, including AD and FTLD. In this framework, the
      purpose of this review is to give an overview of clinical features, genetics, and
      novel discoveries on biomolecular pathogenic mechanisms at the basis of these two
      neurodegenerative diseases and to outline current evidence regarding the role
      played by activated microglia in their pathogenesis. 

PMID- 23970928
TI  - Moxibustion Inhibits the ERK Signaling Pathway and Intestinal Fibrosis in Rats
      with Crohn's Disease.
AB  - Intestinal fibrosis is the main pathological process in Crohn's disease (CD);
      acupuncture and moxibustion can inhibit the process of fibrosis in CD rats, but
      the regulatory mechanism remains unknown. The present study observed the effect
      of moxibustion on the extracellular signal-regulated kinase (ERK) signaling
      pathway in the CD rat. The result shows that the phosphorylation of the Ras, Raf
      1, MEK-1, and ERK-1/2 proteins and the expression of the corresponding mRNAs in
      the colon tissue of CD rat were significantly higher than the normal control
      group. Both treatments with mild moxibustion and with herb-separated moxibustion
      significantly reduced the expression of the Ras, Raf-1, MEK-1, and ERK-1/2
      proteins and Ras and Raf-1 mRNA. MEK-1 and ERK-1/2 mRNA expression in each
      treatment group showed a downward trend, and the ERK-1/2 mRNA levels were
      significantly lower in the mild moxibustion group. It indicates that Ras, Raf-1,
      MEK-1, and ERK-1/2 are involved in the process of intestinal fibrosis in CD rats.
      Moxibustion can downregulate the abnormal expression of colonic Ras, Raf-1, MEK
      1, and ERK-1/2 protein and mRNA levels in CD intestinal fibrosis in rats.
      Moxibustion may play a role in the treatment of CD intestinal fibrosis by
      regulating ERK signaling pathway. 

PMID- 23970929
TI  - Reduced use of emergency care and hospitalization in patients with traumatic
      brain injury receiving acupuncture treatment.
AB  - Background. Little research exists on acupuncture treatment's effect on patients
      with traumatic brain injury (TBI). Methods. Using Taiwan's National Health
      Insurance Research Database, we conducted a cohort study to compare the use of
      emergency care and hospitalization in TBI patients with and without acupuncture
      treatment in the first year after TBI. The adjusted relative risks (RRs) and 95%
      confidence intervals (CIs) of high use of emergency care and hospitalization
      associated with acupuncture treatment were calculated in multivariate Poisson
      regression models with generalized estimating equation. Results. The means of
      medical visits of emergency care and hospitalization were lower in TBI patients
      with acupuncture treatment than in those without acupuncture treatment. After
      adjustment, acupuncture treatment was associated with decreased risk of high
      emergency care visits (beta = -0.0611, P = 0.0452) and hospitalization (beta = 
      0.0989, P < 0.0001). The RRs of high medical visits and expenditure for
      hospitalization associated with acupuncture treatment were 0.62 (95% CI = 0.50
      0.76) and 0.66 (95% CI = 0.53-0.83), respectively. Conclusion. Patients with TBI
      who receive acupuncture treatment have reduced the use of emergency care and
      hospitalization in the first year after injury. The mechanisms of effects of
      acupuncture on TBI warrant further investigations. 

PMID- 23970930
TI  - Inhibitory Effect of the Hexane Fraction of the Ethanolic Extract of the Fruits
      of Pterodon pubescens Benth in Acute and Chronic Inflammation.
AB  - Fruits of Pterodon pubescens Benth have been used traditionally for the treatment
      of rheumatism, sore throat, and respiratory disorders, and also as anti
      inflammatory, analgesic, depurative, tonic, and hypoglycemic agent. The study was
      aimed at evaluating the anti-inflammatory activity of the hexane fraction of an
      ethanolic extract of P. pubescens fruits. The oil from P. pubescens fruits was
      extracted with ethanol and partitioned with hexane. The anti-inflammatory
      activity was measured with increasing doses of the hexane fraction (FHPp) by
      using a carrageenan-induced rat model of pleurisy and a rat model of complete
      Freund's adjuvant-induced arthritis by using an FHPp dose of 250 mg/kg for 21
      days. Treatment with an FHPp resulted in anti-inflammatory activity in both
      models. The results of biochemical, hematological, and histological analyses
      indicated a significant decrease in glucose, cholesterol, and triglycerides
      levels (18.32%, 34.20%, and 41.70%, resp.) and reduction in the numbers of total
      leukocytes and mononuclear cells. The FHPp dose of 1000 mg/kg induced no changes
      in behavioral parameters, and no animal died. The results of this study extend
      the findings of previous reports that have shown that administration of extracts
      and fractions obtained from species of the genus Pterodon exhibits anti
      inflammatory activity and lacks toxicity. 

PMID- 23970931
TI  - Proteomic analysis of the effect of acupuncture on the suppression of kainic Acid
      induced neuronal destruction in mouse hippocampus.
AB  - Kainic acid (KA) is a neurotoxin that induces epileptic seizures and
      excitotoxicity in the hippocampus. Acupuncture is frequently used as an
      alternative therapy for epilepsy, and it has been known to protect hippocampal
      neurons against KA toxicity. Using proteomic analysis, we investigated protein
      expression changes in the hippocampus following acupuncture stimulation at HT8.
      Eight-week-old male C57BL/6 mice (20-25 g) received acupuncture treatment at HT8
      acupoint bilaterally once a day for 3 days and were then administered KA (30
      mg/kg) intraperitoneally. Twenty-four hours after KA injection, neuronal survival
      and astrocyte activation in the hippocampus were measured, and protein expression
      in the hippocampus was identified by 2-dimensional electrophoresis. Acupuncture
      stimulation at HT8 suppressed KA-induced neuronal death and astrocyte activation
      in the hippocampus. We identified the changes in the expression of 11 proteins by
      KA or acupuncture stimulation at HT8 and found that acupuncture stimulation at
      HT8 normalized the expression of dihydropyrimidinase-related protein 2 and
      upregulated the expression of transcriptional activator protein pur-alpha,
      serine/threonine-protein phosphatase 5, and T-complex protein 1 subunit alpha,
      which are related to the survival of neurons. These results suggest that
      acupuncture stimulation at HT8 changes protein expression profiles in the
      hippocampus in favor of neuronal survival in KA-treated mice. 

PMID- 23970932
TI  - Curcumin Suppresses Metastasis via Sp-1, FAK Inhibition, and E-Cadherin
      Upregulation in Colorectal Cancer.
AB  - Colorectal cancer (CRC) is a serious public health problem that results due to
      changes of diet and various environmental stress factors in the world. Curcumin
      is a traditional medicine used for treatment of a wide variety of tumors.
      However, antimetastasis mechanism of curcumin on CRC has not yet been completely
      investigated. Here, we explored the underlying molecular mechanisms of curcumin
      on metastasis of CRC cells in vitro and in vivo. Curcumin significantly inhibits
      cell migration, invasion, and colony formation in vitro and reduces tumor growth
      and liver metastasis in vivo. We found that curcumin suppresses Sp-1
      transcriptional activity and Sp-1 regulated genes including ADEM10, calmodulin,
      EPHB2, HDAC4, and SEPP1 in CRC cells. Curcumin inhibits focal adhesion kinase
      (FAK) phosphorylation and enhances the expressions of several extracellular
      matrix components which play a critical role in invasion and metastasis. Curcumin
      reduces CD24 expression in a dose-dependent manner in CRC cells. Moreover, E
      cadherin expression is upregulated by curcumin and serves as an inhibitor of EMT.
      These results suggest that curcumin executes its antimetastasis function through
      downregulation of Sp-1, FAK, and CD24 and by promoting E-cadherin expression in
      CRC cells. 

PMID- 23970933
TI  - Research on effects of the thermal stimulation by moxibustion at different
      temperatures on cardiac function in rats and on mast cells in the local site of
      moxibustion.
AB  - Objective. To observe effects of the thermal stimulation by moxibustion at
      different temperatures on cardiac function in brachycardia rat model and on mast
      cells in the local site of moxibustion at the Ximen Acupoint and to compare the
      differences of the effects of moxibustion at different temperatures. Method.
      Establish the brachycardia rat model with propranolol and observe effects of the
      thermal stimulation by moxibustion at different temperatures (38 degrees C and 46
      degrees C). Results. The thermal stimulation by moxibustion at 2 temperatures may
      increase HR, MAP, LVSP, and +dp/dtmax and reduce t-dp/dtmax in brachycardia rats;
      the 46 degrees C moxibustion group shows greater regulating effects on cardiac
      function in rats than that in the 38 degrees C moxibustion group (P < 0.05). The
      thermal stimulation by moxibustion at 2 temperatures may promote degranulation of
      mast cells in the local site of moxibustion at the Ximen Acupoint; the
      degranulation rate in the 46 degrees C moxibustion group is higher than that in
      the 38 degrees C moxibustion group (P < 0.05). Conclusion. There is a certain
      association between the effect on the target organ and the effect in the local
      site of moxibustion. The moxibustion effect possibly resulted from local mast
      cells degranulation and different thermoreceptors activated by the thermal
      stimulation at different temperatures. 

PMID- 23970934
TI  - An In Vivo and In Vitro Evaluation of the Mutual Interactions between the Lung
      and the Large Intestine.
AB  - One of the most important theories of the traditional Chinese medicine is the
      exterior-interior relationship between the lung and the large intestine; so far,
      little direct experimental evidence has been reported to support such
      relationship. Here we for the first time investigated the mutual interactions
      between the lung and the large intestine by examining the relevancies between the
      pulmonary functions and the rectal resting pressure in the rat models of asthma
      and constipation. We also evaluated the effects of the lung homogenate and the
      large intestine homogenate on the isolated large intestine muscle strip and the
      isolated tracheal spiral, respectively. Our results showed that the pulmonary
      resistance and pulmonary compliance were closely related to the rectal resting
      pressure in the asthmatic rat model, while the rectal resting pressure was much
      correlated with the pulmonary resistance in the rat model of constipation.
      Moreover, it was shown that the lung homogenate could specifically contract the
      isolated large intestine muscle strip. Overall, this study provided new lines of
      evidence for the theory and highlighted the potential application in the
      treatment of the corresponding diseases. 

PMID- 23970936
TI  - Antioxidant effects of quercetin and naringenin are associated with impaired
      neutrophil microbicidal activity.
AB  - Naringenin and quercetin are considered antioxidant compounds with promising
      activity against oxidative damage in human cells. However, no reports have
      described their effects on reactive oxygen species (ROS) production by phagocytes
      during microbicidal activity. Thus, the present study evaluated the effects of
      naringenin and quercetin on ROS production, specifically hypochlorous acid
      (HOCl), and their involvement in the microbicidal activity of neutrophils.
      Naringenin and quercetin inhibited HOCl production through different systems, but
      this inhibition was more pronounced for quercetin, even in the cell-free systems.
      With regard to the microbicidal activity of neutrophils, both naringenin and
      quercetin completely inhibited the killing of Staphylococcus aureus. Altogether,
      these data indicate that the decrease in the oxidant activity of neutrophils
      induced by these compounds directly impaired the microbicidal activity of
      neutrophils. Naringenin and quercetin exerted their effects by controlling the
      effector mechanisms of ROS production, with both positive and negative effects of
      these antioxidant agents in oxidative stress conditions and on ROS in the
      microbicidal activity of phagocytes. The present results challenge the
      traditional view of antioxidants as improvers of pathological conditions. 

PMID- 23970935
TI  - Multiple molecular and cellular mechanisms of action of lycopene in cancer
      inhibition.
AB  - Epidemiological studies suggest that including fruits, vegetables, and whole
      grains in regular dietary intake might prevent and reverse cellular
      carcinogenesis, reducing the incidence of primary tumours. Bioactive components
      present in food can simultaneously modulate more than one carcinogenic process,
      including cancer metabolism, hormonal balance, transcriptional activity, cell
      cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies
      have shown an inverse correlation between a diet rich in fruits, vegetables, and
      carotenoids and a low incidence of different types of cancer. Lycopene, the
      predominant carotenoid found in tomatoes, exhibits a high antioxidant capacity
      and has been shown to prevent cancer, as evidenced by clinical trials and studies
      in cell culture and animal models. In vitro studies have shown that lycopene
      treatment can selectively arrest cell growth and induce apoptosis in cancer cells
      without affecting normal cells. In vivo studies have revealed that lycopene
      treatment inhibits tumour growth in the liver, lung, prostate, breast, and colon.
      Clinical studies have shown that lycopene protects against prostate cancer. One
      of the main challenges in cancer prevention is the integration of new molecular
      findings into clinical practice. Thus, the identification of molecular biomarkers
      associated with lycopene levels is essential for improving our understanding of
      the mechanisms underlying its antineoplastic activity. 

PMID- 23970937
TI  - Tocotrienol Attenuates Stress-Induced Gastric Lesions via Activation of
      Prostaglandin and Upregulation of COX-1 mRNA.
AB  - The present study aims to distinguish the effect of tocotrienol on an important
      gastric protective factor, prostaglandin E2 (PGE2), in stress-induced gastric
      injury. Twenty-eight Wistar rats were divided into four groups of seven rats
      each. Two control groups were fed commercial rat diet, and two treatment groups
      were fed the same diet but with additional dose of omeprazole (20 mg/kg) or
      tocotrienol (60 mg/kg). After 28 days, rats from one control group and both
      treated groups were subjected to water-immersion restraint stress for 3.5 hours
      once. The rats were then sacrificed, their stomach isolated and gastric juice
      collected, lesions examined, and gastric PGE2 content and cyclooxygenase (COX)
      mRNA expression were determined. Both the regimes significantly attenuated the
      total lesion area in the stomach compared to the control. Gastric acidity, which
      was increased in stress, was significantly reduced in rats supplemented with
      omeprazole and tocotrienol. The PGE2 content was also significantly higher in the
      rats given tocotrienol supplementation compared to the control followed by an
      increase in COX-1 mRNA expression. We conclude that tocotrienol supplementation
      protected rat gastric mucosa against stress-induced lesions possibly by reducing
      gastric acidity and preserving gastric PGE2 by increasing COX-1 mRNA. 

PMID- 23970938
TI  - Acute and Chronic Toxicity of an Aqueous Fraction of the Stem Bark of
      Stryphnodendron adstringens (Barbatimao) in Rodents.
AB  - Stryphnodendron adstringens has a high tannin content and is used as an
      antiseptic and antimicrobial and in the treatment of leucorrhea, gonorrhea, wound
      healing, and gastritis. The present study evaluated the toxic effects of the
      heptamer prodelphinidin (F2) from the stem bark of S. adstringens in rodents. In
      the acute toxicity test, the mice that received oral doses exhibited reversible
      effects, with an LD50 of 3.015 mg . kg(-1). In the chronic toxicity test at 90
      days, Wistar rats were treated with different doses of F2 (10, 100, and 200 mg .
      kg(-1)). In the biochemical, hematological, and histopathological examinations
      and open-field test, the different dose groups did not exhibit significant
      differences compared with controls. The present results indicate that F2 from the
      stem bark of S. adstringens caused no toxicity with acute and chronic oral
      treatment in rodents at the doses administered. 

PMID- 23970939
TI  - Comparison of Brazilian Plants Used to Treat Gastritis on the Oxidative Burst of
      Helicobacter pylori-Stimulated Neutrophil.
AB  - Ten Brazilian medicinal plants used to treat gastritis and ulcers were carefully
      selected on the basis of ethnopharmacological importance and antiulcerogenic
      activity previously described. The antioxidant activity of the methanolic
      extracts was determined in analysis conditions that simulate a real biological
      activity on inhibition of the oxidative burst induced in neutrophils using
      Helicobacter pylori as activator, by a luminol-amplified chemiluminescence assay.
      The extracts, at low concentration (5  MU g/mL), exhibited a large variation in
      inhibitory effects of H. pylori-induced oxidative burst ranging from 48%
      inhibition to inactive, but all extracts, excluding Byrsonima intermedia, had
      inhibitory activity over 80% at the concentration of 100  MU g/mL. The total
      suppressive antioxidant capacity measured as the effective concentration, which
      represents the extract concentration producing 50% inhibition of the
      chemiluminescence induced by H. pylori, varies from 27.2 to 56.8  MU g/mL and was
      in the following order: Qualea parviflora > Qualea multiflora > Alchornea
      triplinervia > Qualea grandiflora > Anacardium humile > Davilla elliptica >
      Mouriri pusa > Byrsonima basiloba > Alchornea glandulosa > Byrsonima intermedia.
      The main groups of compounds in tested extracts are presented. Differences in the
      phytochemical profile, quantitatively and qualitatively, of these plants can
      explain and justify their protective effect on the gastric mucosa caused by the
      neutrophil-generated ROS that occurs when H. pylori displays its evasion
      mechanisms. 

PMID- 23970940
TI  - Electroacupuncture Could Regulate the NF-kappaB Signaling Pathway to Ameliorate
      the Inflammatory Injury in Focal Cerebral Ischemia/Reperfusion Model Rats.
AB  - The activated nuclear factor-KappaB signaling pathway plays a critical role in
      inducing inflammatory injury. It has been reported that electroacupuncture could
      be an effective anti-inflammatory treatment. We aimed to explore the complex
      mechanism by which EA inhibits the activation of the NF- kappa B signal pathway
      and ameliorate inflammatory injury in the short term; the effects of NEMO Binding
      Domain peptide for this purpose were compared. Focal cerebral I/R was induced by
      middle cerebral artery occlusion for 2 hrs. Total 380 male Sprague-Dawley rats
      are in the study. The neurobehavioral scores, infarction volumes, and the levels
      of IL-1 beta and IL-13 were detected. NF- kappa B p65, I kappa B alpha , IKK
      alpha , and IKK beta were analyzed and the ability of NF- kappa B binding DNA was
      investigated. The EA treatment and the NBD peptide treatment both reduced infarct
      size, improved neurological scores, and regulated the levels of IL-1 beta and IL
      13. The treatment reduced the expression of IKK alpha and IKK beta and altered
      the expression of NF- kappa B p65 and I kappa B alpha in the cytoplasm and
      nucleus; the activity of NF- kappa B was effectively reduced. We conclude that EA
      treatment might interfere with the process of NF- kappa B nuclear translocation.
      And it also could suppress the activity of NF- kappa B signaling pathway to
      ameliorate the inflammatory injury after focal cerebral ischemia/reperfusion. 

PMID- 23970941
TI  - Pomegranate juice augments memory and FMRI activity in middle-aged and older
      adults with mild memory complaints.
AB  - Despite increasing emphasis on the potential of dietary antioxidants in
      preventing memory loss and on diet as a precursor of neurological health,
      rigorous studies investigating the cognitive effects of foods and their
      components are rare. Recent animal studies have reported memory and other
      cognitive benefits of polyphenols, found abundantly in pomegranate juice. We
      performed a preliminary, placebo-controlled randomized trial of pomegranate juice
      in older subjects with age-associated memory complaints using memory testing and
      functional brain activation (fMRI) as outcome measures. Thirty-two subjects (28
      completers) were randomly assigned to drink 8 ounces of either pomegranate juice
      or a flavor-matched placebo drink for 4 weeks. Subjects received memory testing,
      fMRI scans during cognitive tasks, and blood draws for peripheral biomarkers
      before and after the intervention. Investigators and subjects were all blind to
      group membership. After 4 weeks, only the pomegranate group showed a significant
      improvement in the Buschke selective reminding test of verbal memory and a
      significant increase in plasma trolox-equivalent antioxidant capacity (TEAC) and
      urolithin A-glucuronide. Furthermore, compared to the placebo group, the
      pomegranate group had increased fMRI activity during verbal and visual memory
      tasks. While preliminary, these results suggest a role for pomegranate juice in
      augmenting memory function through task-related increases in functional brain
      activity. 

PMID- 23970942
TI  - Classification of pulmonary nodules by using hybrid features.
AB  - Early detection of pulmonary nodules is extremely important for the diagnosis and
      treatment of lung cancer. In this study, a new classification approach for
      pulmonary nodules from CT imagery is presented by using hybrid features. Four
      different methods are introduced for the proposed system. The overall detection
      performance is evaluated using various classifiers. The results are compared to
      similar techniques in the literature by using standard measures. The proposed
      approach with the hybrid features results in 90.7% classification accuracy (89.6%
      sensitivity and 87.5% specificity). 

PMID- 23970943
TI  - A QR code based zero-watermarking scheme for authentication of medical images in
      teleradiology cloud.
AB  - Healthcare institutions adapt cloud based archiving of medical images and patient
      records to share them efficiently. Controlled access to these records and
      authentication of images must be enforced to mitigate fraudulent activities and
      medical errors. This paper presents a zero-watermarking scheme implemented in the
      composite Contourlet Transform (CT)-Singular Value Decomposition (SVD) domain for
      unambiguous authentication of medical images. Further, a framework is proposed
      for accessing patient records based on the watermarking scheme. The patient
      identification details and a link to patient data encoded into a Quick Response
      (QR) code serves as the watermark. In the proposed scheme, the medical image is
      not subjected to degradations due to watermarking. Patient authentication and
      authorized access to patient data are realized on combining a Secret Share with
      the Master Share constructed from invariant features of the medical image. The
      Hu's invariant image moments are exploited in creating the Master Share. The
      proposed system is evaluated with Checkmark software and is found to be robust to
      both geometric and non geometric attacks. 

PMID- 23970945
TI  - Neonatal purpura fulminans manifestation in early-onset group B Streptococcal
      infection.
AB  - PATIENT: Male, 0 FINAL DIAGNOSIS: Purpura fulminans Symptoms: Fever * letargy
      MEDICATION: - Clinical Procedure: - Specialty: Pediatrics and Neonatology.
      OBJECTIVE: Rare disease. BACKGROUND: Neonatal purpura fulminans (PF) is a rare
      but frequently fatal disorder associated with high morbidity and mortality. It
      may be congenital, as a result of protein C and S deficiency, or acquired due to
      severe infection. Gram-negative organisms and Staphylococcus species are the most
      common causes of the acute infectious type, and a few cases of causative neonatal
      group B Streptococcus (GBS) disease have been reported worldwide. CASE REPORT: We
      present a full-term male neonate with purpura fulminans secondary to early-onset
      group B streptococcal (GBS) infection. The mother brought the infant to the
      emergency department at the age of 43 hours of life, with fever (39.5 degrees C)
      and lethargy. Neonatal sepsis was suspected, and he was immediately started on
      intravenous ampicillin and gentamicin. The initial workup revealed disseminated
      intravascular coagulopathy, and both blood and CSF cultures grew GBS. He had
      normal levels of protein C and protein S for his age. The infant died 48 hours
      after admission due to multiorgan system failure despite aggressive neonatal
      intensive care support. CONCLUSIONS: Neonatal PF secondary to early-onset GBS
      infection is a fatal condition that should not be missed. Screening pregnant
      women for GBS colonization and use of protocols for preventing perinatal GBS
      infection is considered the most important preventive measure of this fatal
      condition, especially among Saudi women, who have a relatively high rate of GBS
      infection.

PMID- 23970944
TI  - Bioinformatics resources and tools for conformational B-cell epitope prediction.
AB  - Identification of epitopes which invoke strong humoral responses is an essential
      issue in the field of immunology. Localizing epitopes by experimental methods is
      expensive in terms of time, cost, and effort; therefore, computational methods
      feature for its low cost and high speed was employed to predict B-cell epitopes.
      In this paper, we review the recent advance of bioinformatics resources and tools
      in conformational B-cell epitope prediction, including databases, algorithms, web
      servers, and their applications in solving problems in related areas. To
      stimulate the development of better tools, some promising directions are also
      extensively discussed. 

PMID- 23970946
TI  - Rapidly developing yeast microcolonies differentiate in a similar way to aging
      giant colonies.
AB  - During their development and aging on solid substrates, yeast giant colonies
      produce ammonia, which acts as a quorum sensing molecule. Ammonia production is
      connected with alkalization of the surrounding medium and with extensive
      reprogramming of cell metabolism. In addition, ammonia signaling is important for
      both horizontal (colony centre versus colony margin) and vertical (upper versus
      lower cell layers) colony differentiations. The centre of an aging differentiated
      giant colony is thus composed of two major cell subpopulations, the subpopulation
      of long-living, metabolically active and stress-resistant cells that form the
      upper layers of the colony and the subpopulation of stress-sensitive starving
      cells in the colony interior. Here, we show that microcolonies originating from
      one cell pass through similar developmental phases as giant colonies. Microcolony
      differentiation is linked to ammonia signaling, and cells similar to the upper
      and lower cells of aged giant colonies are formed even in relatively young
      microcolonies. A comparison of the properties of these cells revealed a number of
      features that are similar in microcolonies and giant colonies as well as a few
      that are only typical of chronologically aged giant colonies. These findings show
      that colony age per se is not crucial for colony differentiation. 

PMID- 23970947
TI  - Adenine nucleotide translocase, mitochondrial stress, and degenerative cell
      death.
AB  - Mitochondria are intracellular organelles involved in ATP synthesis, apoptosis,
      calcium signaling, metabolism, and the synthesis of critical metabolic cofactors.
      Mitochondrial dysfunction is associated with age-related degenerative diseases.
      How mitochondrial dysfunction causes cell degeneration is not well understood.
      Recent studies have shown that mutations in the adenine nucleotide translocase
      (Ant) cause aging-dependent degenerative cell death (DCD) in yeast, which is
      sequentially manifested by inner membrane stress, mitochondrial DNA (mtDNA) loss,
      and progressive loss of cell viability. Ant is an abundant protein primarily
      involved in ADP/ATP exchange across the mitochondrial inner membrane. It also
      mediates basal proton leak and regulates the mitochondrial permeability
      transition pore. Missense mutations in the human Ant1 cause several degenerative
      diseases which are commonly manifested by fractional mtDNA deletions. Multiple
      models have been proposed to explain the Ant1-induced pathogenesis. Studies from
      yeast have suggested that in addition to altered nucleotide transport properties,
      the mutant proteins cause a global stress on the inner membrane. The mutant
      proteins likely interfere with general mitochondrial biogenesis in a dominant
      negative manner, which secondarily destabilizes mtDNA. More recent work revealed
      that the Ant-induced DCD is suppressed by reduced cytosolic protein synthesis.
      This finding suggests a proteostatic crosstalk between mitochondria and the
      cytosol, which may play an important role for cell survival during aging. 

PMID- 23970948
TI  - 50 Hz electromagnetic field produced changes in FTIR spectroscopy associated with
      mitochondrial transmembrane potential reduction in neuronal-like SH-SY5Y cells.
AB  - SH-SY5Y neuroblastoma cells were used as an experimental model to study the
      effects of 50 Hz electromagnetic field, in the range from 50 u T to 1.4 mT.
      Fourier transform infrared spectroscopy analysis evidenced a reduction in
      intensity of the amide A band and a slight increase of vibration bands at 2921
      cm(-1) and 2853 cm(-1) corresponding to methylene groups. A further increase of
      the magnetic field intensity of exposure up to 0.8 mT and 1.4 mT produced a clear
      increase in intensity of CH2 vibration bands. Moreover, it has been observed some
      alterations in the amide I region, such as a shifted peak of the amide I band to
      a smaller wavenumber, probably due to protein conformational changes. These
      results suggested that exposure to extremely low electromagnetic fields
      influenced lipid components of cellular membrane and the N-H in-plane bending and
      C-N stretching vibrations of peptide linkages, modifying the secondary structures
      of alpha -helix and beta -sheet contents and producing unfolding process in cell
      membrane proteins. The observed changes after exposure to 50 Hz electromagnetic
      field higher than 0.8 mT were associated with a significant reduction of cell
      viability and reduced mitochondrial transmembrane potential.

PMID- 23970951
TI  - Check in the Mail or More in the Paycheck: Does the Effectiveness of Fiscal
      Stimulus Depend on How It Is Delivered?
AB  - Recent fiscal policies, including the 2008 stimulus payments and the 2009 Making
      Work Pay Tax Credit, aimed to increase household spending. This paper quantifies
      the spending response to these policies and examines differences in spending by
      whether the stimulus was delivered as a one-time payment or as a flow of payments
      from reduced withholding. Based on responses from a representative sample of
      households in the Thomson Reuters University of Michigan Surveys of Consumers,
      the paper finds that the reduction in withholding in 2009 boosted spending at
      roughly half the rate (13 percent) as the one-time payments (25 percent) in 2008.

PMID- 23970949
TI  - Role of mitochondria in HIV infection and associated metabolic disorders: focus
      on nonalcoholic fatty liver disease and lipodystrophy syndrome.
AB  - Highly active antiretroviral therapy (HAART) has considerably improved the
      prognosis of HIV-infected patients. However, prolonged use of HAART has been
      related to long-term adverse events that can compromise patient health such as
      HIV-associated lipodystrophy syndrome (HALS) and nonalcoholic fatty liver disease
      (NAFLD). There is consistent evidence for a central role of mitochondrial
      dysfunction in these pathologies. Nucleotide reverse transcriptase inhibitors
      (NRTIs) have been described to be mainly responsible for mitochondrial
      dysfunction in adipose tissue and liver although nonnucleoside transcriptase
      inhibitors (NNRTIs) or protease inhibitors (PIs) have also showed mitochondrial
      toxicity, which is a major concern for the selection and the long-term adherence
      to a particular therapy. Several mechanisms explain these deleterious effects of
      HAART on mitochondria, and evidence points to other mechanisms beyond the "Pol-
      gamma hypothesis." HIV infection has also direct effects on mitochondria. In
      addition to the negative effects described for HIV itself and/or HAART on
      mitochondria, HIV-infected patients are more prone to develop a premature aging
      and, therefore, to present an increased oxidative state that could lead to the
      development of these metabolic disturbances observed in HIV-infected patients. 

PMID- 23970950
TI  - Thiol redox sensitivity of two key enzymes of heme biosynthesis and pentose
      phosphate pathways: uroporphyrinogen decarboxylase and transketolase.
AB  - Uroporphyrinogen decarboxylase (Hem12p) and transketolase (Tkl1p) are key
      mediators of two critical processes within the cell, heme biosynthesis, and the
      nonoxidative part of the pentose phosphate pathway (PPP). The redox properties of
      both Hem12p and Tkl1p from Saccharomyces cerevisiae were investigated using
      proteomic techniques (SRM and label-free quantification) and biochemical assays
      in cell extracts and in vitro with recombinant proteins. The in vivo analysis
      revealed an increase in oxidized Cys-peptides in the absence of Grx2p, and also
      after treatment with H2O2 in the case of Tkl1p, without corresponding changes in
      total protein, demonstrating a true redox response. Out of three detectable Cys
      residues in Hem12p, only the conserved residue Cys52 could be modified by
      glutathione and efficiently deglutathionylated by Grx2p, suggesting a possible
      redox control mechanism for heme biosynthesis. On the other hand, Tkl1p activity
      was sensitive to thiol redox modification and although Cys622 could be
      glutathionylated to a limited extent, it was not a natural substrate of Grx2p.
      The human orthologues of both enzymes have been involved in certain cancers and
      possess Cys residues equivalent to those identified as redox sensitive in yeast.
      The possible implication for redox regulation in the context of tumour
      progression is put forward. 

PMID- 23970952
TI  - Pathology is a critical aspect of preclinical aging studies.
AB  - Experimental design for mouse aging studies has historically involved lifespan,
      but it is now clear that survival data without pathology data limit the
      information that can be obtained on aging animals. This limitation becomes more
      serious when interventions of any sort are implemented. Pathology gives an
      insight into the health of an animal by revealing lesions not readily observable
      in the live animal. As such, it is a snapshot of disease conditions at the time
      of death. Therefore, a long-term goal is to establish pathology information as an
      essential component of studies involving health span and lifespan of aging
      animals. Given that pathology assessment is essential to help define the
      progression of lesions associated with aging, the real challenge is including it
      in aging studies because there is currently a lack of specialized expertise and
      resources. An increase in the level and scope of pathology assessment of tissues
      from old mice involved in aging studies is needed. A focus on the correlation of
      pathology data with longitudinal and cross-sectional lifespan data and health
      span physiology data can be established by enhancing standard histologic
      assessment of lesions observed in tissues from old mice. An environment for the
      development and integration of pathology data into aging studies of mice is
      needed to encourage more pathologists and other scientists to specialize in
      pathology of aging, and establish relevant standards to compare with other
      species including humans. Such results will have an important positive impact on
      aging studies because of the significant empowerment on data analyses and
      interpretation. 

PMID- 23970953
TI  - The Curative and Prophylactic Effects of Xylopic Acid on Plasmodium berghei
      Infection in Mice.
AB  - Efforts have been intensified to search for more effective antimalarial agents
      because of the observed failure of some artemisinin-based combination therapy
      (ACT) treatments of malaria in Ghana. Xylopic acid, a pure compound isolated from
      the fruits of the Xylopia aethiopica, was investigated to establish its
      attributable prophylactic, curative antimalarial, and antipyretic properties. The
      antimalarial properties were determined by employing xylopic acid (10-100 mg/kg)
      in ICR mice infected with Plasmodium berghei. Xylopic acid exerted significant (P
      < 0.05) effects on P. berghei infection similar to artemether/lumefantrine, the
      standard drug. Furthermore, it significantly (P < 0.05) reduced the
      lipopolysaccharide- (LPS-) induced fever in Sprague-Dawley rats similar to
      prednisolone. Xylopic acid therefore possesses prophylactic and curative
      antimalarial as well as antipyretic properties which makes it an ideal
      antimalarial agent. 

PMID- 23970954
TI  - Cajachalcone: An Antimalarial Compound from Cajanus cajan Leaf Extract.
AB  - Cajanus cajan L, a member of the family Fabaceae, was identified from the
      Nigerian antimalarial ethnobotany as possessing antimalarial properties. The
      bioassay-guided fractionation of the crude methanol extract of C. cajan leaves
      was done in vitro using the multiresistant strain of Plasmodium falciparum (K1)
      in the parasite lactate dehydrogenase assay. Isolation of compound was achieved
      by a combination of chromatographic techniques, while the structure of the
      compound was elucidated by spectroscopy. This led to the identification of a
      cajachalcone, 2',6'-dihydroxy-4-methoxy chalcone, as the biologically active
      constituent from the ethyl acetate fraction. Cajachalcone had an IC50 value of
      2.0  MU g/mL (7.4  MU M) and could be a lead for anti-malarial drug discovery. 

PMID- 23970955
TI  - Risk factors for tube shunt exposure: a matched case-control study.
AB  - Purpose. To evaluate potential risk factors for developing tube shunt exposure in
      glaucoma patients. Patients and Methods. Forty-one cases from 41 patients that
      had tube shunt exposure from 1996 to 2005 were identified from the Robert Cizik
      Eye Clinic and Bascom Palmer Eye Institute. Each case was matched with 2 controls
      of the same gender and with tube shunts implanted within 6 months of the index
      case. Conditional logistic regression was used to determine risk factors.
      Results. The study cohort includes a total of 121 eyes from 121 patients. The
      mean age was 63.6 +/- 19.7 years, ranging from 1 to 96 years. The average time to
      exposure was 19.29 +/- 23.75 months (range 0.36-85.74 months). Risk factors
      associated with tube exposure were Hispanic ethnicity (P = 0.0115; OR = 3.6; 95%
      CI, 1.3-9.7), neovascular glaucoma (P = 0.0064; OR = 28.5; 95% CI, 2.6-316.9),
      previous trabeculectomy (P = 0.0070; OR = 5.3; 95% CI, 1.6-17.7), and combined
      surgery (P = 0.0381; OR = 3.7; 95% CI, 1.1-12.7). Conclusions. Hispanic
      ethnicity, neovascular glaucoma, previous trabeculectomy, and combined surgery
      were identified as potential risk factors for tube shunt exposure. These
      potential risk factors should be considered when determining the indication for
      performing tube shunt implantation and the frequency of long-term followup. 

PMID- 23970956
TI  - Simultaneous Use of MutS and RecA for Suppression of Nonspecific Amplification
      during PCR.
AB  - Thermus thermophilus MutS, a thermostable mismatch-recognizing protein, is
      utilized in PCR to suppress nonspecific amplification by preventing synthesis
      from mismatched primers. T. thermophilus RecA also decreases nonspecific
      amplification by promoting proper hybridization between the primer and template.
      We observed that MutS and RecA function under the same reaction conditions and
      that MutS and RecA do not preclude each other. Furthermore, there were some DNA
      sequences for which only one of the 2 proteins effectively suppressed nonspecific
      amplification. The simultaneous use of MutS and RecA is a more attractive error
      suppressing technique than the use of either of the 2 proteins alone. 

PMID- 23970957
TI  - Ambulatory Blood Pressure Monitoring in a Cohort of Children Referred with
      Suspected Hypertension: Characteristics of Children with and without Attention
      Deficit Hyperactivity Disorder.
AB  - Childhood hypertension's increasing prevalence has generally been linked to the
      obesity epidemic. We observed that a significant proportion of children referred
      to our pediatric center with documented office hypertension are nonobese and have
      a history of attention deficit hyperactivity disorder (ADHD). To define the
      extent of this anecdotal observation, we performed a retrospective analysis of
      ambulatory blood pressure monitoring (ABPM) tests which in our center are
      routinely performed in newly referred children suspected of hypertension. Twenty
      one percent (48 of 227 new referrals) had a history of ADHD, and 81% of them were
      treated with psychostimulant medications at the time of their ABPM test. Children
      in this group had a significantly lower average BMI z-score compared with the
      rest of the children (0.18 versus 0.75) and were significantly more likely to
      have abnormally elevated wake systolic loads on ABPM (38% versus 4%). The overall
      proportion of children with any abnormality on ABPM was comparable in both groups
      (46% versus 40%). Conclusion. A significant proportion of children suspected of
      hypertension have ADHD which may be related to higher wake systolic BP values.
      The prevalence of hypertension among children with ADHD will have to be
      determined in prospective studies. 

PMID- 23970958
TI  - Pathophysiology of vascular remodeling in hypertension.
AB  - Vascular remodeling refers to alterations in the structure of resistance vessels
      contributing to elevated systemic vascular resistance in hypertension. We start
      with some historical aspects, underscoring the importance of Glagov's
      contribution. We then move to some basic concepts on the biomechanics of blood
      vessels and explain the definitions proposed by Mulvany for specific forms of
      remodeling, especially inward eutrophic and inward hypertrophic. The available
      evidence for the existence of remodeled resistance vessels in hypertension comes
      next, with relatively more weight given to human, in comparison with animal data.
      Mechanisms are discussed. The impact of antihypertensive drug treatment on
      remodeling is described, again with emphasis on human data. Some details are
      given on the three mechanisms to date which point to remodeling resistance
      arteries as an independent predictor of cardiovascular risk in hypertensive
      patients. We terminate by considering the potential role of remodeling in the
      pathogenesis of endorgan damage and in the perpetuation of hypertension. 

PMID- 23970959
TI  - Mediators of pruritus in lichen planus.
AB  - Lichen planus (LP) is an inflammatory mucocutaneous disease, showing a wide
      variety of clinical subtypes. The classic presentation of LP involves the
      appearance of polygonal, flat-topped, violaceous papules and plaques with
      reticulated white lines, termed "Wickham's striae". Cutaneous lesions tend to be
      extremely pruritic, and this symptom does not subside after common antipruritic
      treatment. Moreover, based on our previous pilot study, it could be stated, that
      itch is the most unpleasant and bothersome symptom of LP for majority of patients
      suffering from this disease. However, the underlying mechanisms of itch in lichen
      planus remain still unknown. In addition, there is no study on mediators of this
      sensation, but taking into account pathogenesis of LP there are some possible
      mediators implicated to transmit or modulate itch. In pathogenesis of LP
      important are such mechanisms as apoptosis, autoimmune reaction, and role of
      stress. With these pathways some, previously described in other diseases, itch
      mediators such as cytokines, proteases, and opioid system are connected. Whether
      these mechanisms are involved in pruritus accompanying LP requires further
      investigation. Limited knowledge of pruritus origin in lichen planus is
      responsible for the lack of the effective antipruritic treatments. Here, we
      describe possible mechanisms participating the pathogenesis of pruritus in lichen
      planus. 

PMID- 23970960
TI  - Prevalence of childhood and adolescent overweight and obesity from 2003 to 2010
      in an integrated health care delivery system.
AB  - An observational study of the Kaiser Permanente Northern California (KPNC) BMI
      coding distributions was conducted to ascertain the trends in overweight and
      obesity prevalence among KPNC members aged 2-19 between the periods of 2003-2005
      and 2009-2010. A decrease in the prevalence of overweight (-11.1% change) and
      obesity (-3.6% change) and an increase in the prevalence of healthy weight (+2.7%
      change) were demonstrated. Children aged 2-5 had the greatest improvement in
      obesity prevalence (-11.5% change). Adolescents aged 12-19 were the only age
      group to not show a decrease in obesity prevalence. Of the racial and ethnic
      groups, Hispanics/Latinos had the highest prevalence of obesity across all age
      groups. The KPNC prevalence of overweight and obesity compares favorably to
      external benchmarks, although differences in methodologies limit our ability to
      draw conclusions. Physician counseling as well as weight management programs and
      sociodemographic factors may have contributed to the overall improvements in BMI
      in the KPNC population. Physician training, practice tools, automated BMI
      reminders and performance feedback improved the frequency and quality of
      physician counseling. BMI screening and counseling at urgent visits, in addition
      to well-child care visits, increased the reach and dose of physician counseling. 

PMID- 23970961
TI  - Risk of anaemia in population of healthy young people inhabiting a region in
      central europe.
AB  - It is quite unbelievable but significant percentage of young healthy women is at
      risk of anaemia despite proper nutritional state. In this study we decided to
      determine the lack or excess of which nutrients in a diet can lead to any
      effects. The major cause of anaemia is not, as in many studies on nutritional
      status, the deficiency in iron in a diet. Iron intake in women with anaemia
      exceeded AI (Adequate Intake) level. 120 people took part in the study. Average
      HGB concentration in female group amounted to 12.45 g/dL and in male group to
      14.35 g/dL. Anaemia was determined in 29% women and 4.2% men. In group of women
      with anaemia a statistically higher intake of SFA, cholesterol, and sucrose and
      lower intake of pyridoxine, folacin, niacin, and vitamin E, Mn, Cu, Zn, Fe, and
      Mg were determined. In a group of men with low haemoglobin concentration a
      statistically higher intake of sucrose but lower intake of fat, especially SFA
      and MUFA, vitamin C and zinc were observed. Therefore, together with anaemia in
      the group of women there are coexisting deficiencies in other nutrients, as
      compared to the group of men. Prevention in both groups should include various
      supplements. 

PMID- 23970962
TI  - Rapid Assessment for Coexistence of Vitamin B12 and Iron Deficiency Anemia among
      Adolescent Males and Females in Northern Himalayan State of India.
AB  - Coexistence of folic acid and vitamin B12 deficiency has been observed among
      adolescents with iron deficiency anemia, but limited evidence is available from
      India. So, a rapid assessment was done to study the prevalence of iron, folic
      acid, and vitamin B12 deficiency among adolescent males and females in northern
      Himalayan state in India. Methods. Total 885 (female: 60.9%) adolescents (11 to
      19 completed years) were surveyed from 30-cluster village from two community
      development blocks of Himachal Pradesh. Serum ferritin, folic acid, and vitamin
      B12 were estimated among randomly selected 100 male and 100 female adolescents.
      Results. Under-nutrition (BMI < 18.5 kg/m(2)) was observed among 68.9% of
      adolescents (male: 67.1%; female: 70.7; P = 0.29). Anemia was observed to be
      prevalent among 87.2% males and 96.7% females (P = 0.00). Mild form of anemia was
      observed to be the most common (53.9%) form followed by moderate (29.7%) anemia.
      Strikingly, it was found that all the adolescents were deficient in vitamin B12
      and none of the adolescents was observed to be deficient in folic acid.
      Conclusion. Among both male and female adolescents anemia with vitamin B12
      deficiency was observed to be a significant public health problem. Folic acid
      deficiency was not observed as a problem among surveyed adolescents. 

PMID- 23970963
TI  - High-frequency oscillatory ventilation combined with volume guarantee in a
      neonatal animal model of respiratory distress syndrome.
AB  - Objective. To assess volume guarantee (VG) ventilation combined with high
      frequency oscillatory ventilation (HFOV) strategy on PaCO2 regulation in an
      experimental model of neonatal distress syndrome. Methods. Six 2-day-old piglets
      weighing 2.57 +/- 0.26 kg were used for this interventional experimental study.
      Animals were ventilated during physiologic lung conditions and after depletion of
      lung surfactant by bronchoalveolar lavage (BAL). The effect of HFOV combined with
      VG on PaCO2 was evaluated at different high-frequency expired tidal volume (VThf)
      at constant frequency (f R ) and mean airway pressure (mPaw). Fluctuations of the
      pressure (DeltaPhf) around the mPaw and PaCO2 were analyzed before and after lung
      surfactant depletion. Results. PaCO2 levels were inversely proportional to VThf.
      In the physiological lung condition, an increase in VThf caused a significant
      decrease in PaCO2 and an increase in DeltaPhf. After BAL, PaCO2 did not change as
      compared with pre-BAL situation as the VThf remained constant by the ventilator.
      Conclusions. In this animal model, using HFOV combined with VG, changes in the
      VThf settings induced significant modifications in PaCO2. After changing the lung
      condition by depletion of surfactant, PaCO2 remained unchanged, as the VThf
      setting was maintained constant by modifications in the DeltaPhf done by the
      ventilator. 

PMID- 23970964
TI  - Diagnosis and management of epileptic encephalopathies in children.
AB  - Epileptic encephalopathies refer to a group of disorders in which the unremitting
      epileptic activity contributes to severe cognitive and behavioral impairments
      above and beyond what might be expected from the underlying pathology alone, and
      these can worsen over time leading to progressive cerebral dysfunction. Several
      syndromes have been described based on their electroclinical features (age of
      onset, seizure type, and EEG pattern). This review briefly describes the clinical
      evaluation and management of commonly encountered epileptic encephalopathies in
      children. 

PMID- 23970965
TI  - Type 2 Diabetes Risk among Asian Indians in the US: A Pilot Study.
AB  - The purpose of this pilot study was to investigate type 2 diabetes risk among
      Asian Indians of Kerala ethnicity living in a West Texas County of the USA. The
      study used a descriptive correlational design with thirty-seven adult nondiabetic
      Asian Indian subjects between 20 and 70 years of age. The measurement included
      nonbiochemical indices of obesity, family history of type 2 diabetes, length of
      immigration in the US, history of hypertension, physical activity pattern, and
      fruit and vegetable intake. The majority of the subjects showed an increased
      nonbiochemical indices corresponding with overweight and obesity, placing them at
      risk for type 2 diabetes and associated cardiovascular complications. The
      physical activity pattern indicated a sedentary lifestyle. The decreased physical
      activity was associated with a higher Body Mass Index (BMI) and body fat
      percentage; length of residence in the US greater than 10 years was associated
      with increased body fat percentage and BMI; family history of type 2 diabetes was
      associated with an increase in body fat percentage. Fruit and vegetable intake
      pattern was not associated with a risk for type 2 diabetes. Further studies are
      recommended for risk surveillance among Asian Indian population living in the US.

PMID- 23970966
TI  - Open reduction internal fixation poststernotomy mediastinitis.
AB  - Introduction. Mediastinitis has been reported to complicate 5% of sternotomy
      surgery. We have adopted an open reduction and rigid internal fixation (ORIF)
      approach during the conventional rescue surgery in the treatment of
      mediastinitis. Methods. A retrospective review was performed to compare the
      outcomes of patients that had an ORIF to correct postoperative mediastinitis
      following median sternotomy. These were compared with the outcome of the patients
      that did not undergo ORIF. Results. In the 5-year study period, we reviewed 35
      mediastinitis patient charts. Postoperatively, the ORIF patient group remained in
      the Intensive Care Unit (ICU) and on a ventilator for a mean of 1.5 and 0.75
      days, respectively. Patients treated without ORIF spent significantly more days
      in the ICU (mean of 7.5 days, P < 0.05) and on a ventilator (mean of 2.15 days, P
      = 0.1). Furthermore, it was found that none of the patients (0%) who underwent
      ORIF complained of any postoperative sternal instability or pain. Preoperatively,
      however, these rates were as high as 72%. Conclusions. In the select patient,
      ORIF can be a safe option in the management of mediastinitis, which we have shown
      to significantly decrease morbidity and mortality by providing anatomic reduction
      as well as physiologic stabilization. We have shown that ORIF will improve the
      quality of life of the patient by minimizing abnormal sternal mobility and pain
      and will also decrease inpatient costs by decreasing days spent in the ICU and
      ventilator dependence. 

PMID- 23970967
TI  - Mycobacterial Etiology of Pulmonary Tuberculosis and Association with HIV
      Infection and Multidrug Resistance in Northern Nigeria.
AB  - Objective. Data on pulmonary tuberculosis (TB) caused by Mycobacterium
      tuberculosis (MTB) complex in Nigeria are limited. We investigated species of MTB
      complex in TB cases from northern Nigeria. Methods. New TB suspects were
      enrolled, screened for HIV and their sputum samples were cultured after routine
      microscopy. Genotypes MTBC and MTBDRplus were used to characterize the MTB
      complex species and their resistance to isoniazid and rifampicin. Results. Of the
      1,603 patients enrolled, 375 (23%) had MTB complex infection: 354 (94.4%) had
      Mycobacterium tuberculosis; 20 (5.3%) had Mycobacterium africanum; and one had
      Mycobacterium bovis (0.3%). Cases were more likely to be male (AOR = 1.87, 95% CI
      : 1.42-2.46; P <= 0.001), young (AOR = 2.03, 95% CI : 1.56-2.65; P <= 0.001) and
      have HIV (AOR = 1.43, 95% CI : 1.06-1.92; P = 0.032). In 23 patients (6.1%), the
      mycobacterium was resistant to at least one drug, and these cases were more
      likely to have HIV and prior TB treatment (AOR = 3.62, 95% CI : 1.51-8.84; P =
      0.004; AOR : 4.43; 95% CI : 1.71-11.45 P = 0.002 resp.), compared to cases
      without any resistance. Conclusion. Mycobacterium tuberculosis remained the
      predominant specie in TB in this setting followed by Mycobacterium africanum
      while Mycobacterium bovis was rare. The association of TB drug resistance with
      HIV has implications for TB treatment. 

PMID- 23970968
TI  - Musculoskeletal Pain Disorders among Secondary School Saudi Female Teachers.
AB  - Objective. This study was conducted to estimate prevalence and pattern of
      musculoskeletal pain disorders among secondary school Saudi female teachers in Al
      Khobar area and the psychodemographic and psychosocial factors that may affect
      them. Material and Method. A cross-sectional study was conducted using sample of
      secondary schools teachers (governmental and private school) in Al-Khobar area,
      Saudi Arabia (KSA). Data were collected using a structured self-administered
      questionnaire. Result. Prevalence of musculoskeletal pain disorders was 79.17%.
      Main sites of pain were lower back (63.8%) followed by shoulder (45.4%), neck
      (42.1%), leg (40.0%), wrist (16.2%), and elbow joint (10.0%). Factors that showed
      significant relationship were type of school (p value 0.038), age (p value
      0.002), weight (p value 0.007), number of children (p value 0.006), shoe type (p
      value 0.000), teaching years (p value 0.003), and working daily hours (p value
      0.027). Conclusion. Secondary school female teachers showed high prevalence of
      musculoskeletal pain disorders in most anatomic sites, namely, the back,
      shoulder, neck, legs, wrist, and elbow joint. Risk factors associated with
      significant pain were type of school, age, weight, number of children, and number
      of teaching years. 

PMID- 23970969
TI  - Endovascular treatment of intracranial artery dissection: clinical and
      angiographic follow-up.
AB  - Background. Intracranial artery dissections are rare and many controversies exist
      about treatment options. The aim of this study was to evaluate the efficacy and
      safety of the endovascular approach in patients with an intracranial dissection
      presenting with different symptoms. Methods. We prospectively evaluated the
      clinical features and treatment outcomes of 30 patients who had angiographically
      confirmed nontraumatic intracranial dissections over 4 years. Patients were
      followed up for 17 months, and their final outcomes were assessed by the modified
      Rankin Score (mRS) and angiography. Results. Sixteen (53.3%) patients had a
      dissection of the anterior circulation, whereas 14 (46.7%) had a posterior
      circulation dissection. Overall, 83.3% of the patients suffered a subarachnoid
      hemorrhage (SAH). Grade IV Hunt and Hess score was seen in 32% of the SAH
      presenting cases. Parent artery occlusion (PAO) with coil embolization was used
      in 70% of the cases. The prevalence of overall procedural complications was
      23.3%, and all were completely resolved at the end of follow-up. No evidence of
      in-stent occlusion/stenosis or rebleeding was observed in our cases during follow
      up. Angiography results improved more frequently in the PAO with coil
      embolization group (100%) than in the stent-only-treated group (88.9%) (P =
      0.310) and the unruptured dissection group (5/5, 100%) in comparison with the
      group that presented with SAH (95.8%) (P = 0.833). Conclusion. Favorable outcomes
      were achieved following an endovascular approach for symptomatic ruptured or
      unruptured dissecting aneurysms. However, the long-term efficacy and durability
      of these procedures remain to be determined in a larger series. 

PMID- 23970970
TI  - Presence of contagious yawning in children with autism spectrum disorder.
AB  - Most previous studies suggest diminished susceptibility to contagious yawning in
      children with autism spectrum disorder (ASD). However, it could be driven by
      their atypical attention to the face. To test this hypothesis, children with ASD
      and typically developing (TD) children were shown yawning and control movies. To
      ensure participants' attention to the face, an eye tracker controlled the onset
      of the yawning and control stimuli. Results demonstrated that both TD children
      and children with ASD yawned more frequently when they watched the yawning
      stimuli than the control stimuli. It is suggested therefore that the absence of
      contagious yawning in children with ASD, as reported in previous studies, might
      relate to their weaker tendency to spontaneously attend to others' faces. 

PMID- 23970971
TI  - The neural correlates of mental rotation abilities in cannabis-abusing patients
      with schizophrenia: an FMRI study.
AB  - Growing evidence suggests that cannabis abuse/dependence is paradoxically
      associated with better cognition in schizophrenia. Accordingly, we performed a
      functional magnetic resonance imaging (fMRI) study of visuospatial abilities in
      14 schizophrenia patients with cannabis abuse (DD), 14 nonabusing schizophrenia
      patients (SCZ), and 21 healthy controls (HCs). Participants performed a mental
      rotation task while being scanned. There were no significant differences in the
      number of mistakes between schizophrenia groups, and both made more mistakes on
      the mental rotation task than HC. Relative to HC, SCZ had increased activations
      in the left thalamus, while DD patients had increased activations in the right
      supramarginal gyrus. In both cases, hyper-activations are likely to reflect
      compensatory efforts. In addition, SCZ patients had decreased activations in the
      left superior parietal gyrus compared to both HC and DD patients. This latter
      result tentatively suggests that the neurophysiologic processes underlying
      visuospatial abilities are partially preserved in DD, relative to SCZ patients,
      consistently with the findings showing that cannabis abuse in schizophrenia is
      associated with better cognitive functioning. Further fMRI studies are required
      to examine the neural correlates of other cognitive dysfunctions in schizophrenia
      patients with and without comorbid cannabis use disorder. 

PMID- 23970973
TI  - The Effects of Menorrhagia on Women's Quality of Life: A Case-Control Study.
AB  - Objective. The purpose of this study is to identify menstruation characteristics
      of the women and the effects of menorrhagia on women's quality of life. Methods.
      The study was designed as a descriptive, case-control one. Results. Of the women
      in the case group, 10.9% stated that their menstrual bleeding was severe and very
      severe before complaints while 73.2% described bleeding as severe or very severe
      after complaints. Among those who complained about menorrhagia, 46.7% pointed
      that they used hygienic products that are more protective than regular sanitary
      pads. Women also stated that their clothes, bed linens, and furniture got dirty
      parallel to the severity of the bleeding. In all subscales of SF-36 scale,
      quality of life of the women in the menorrhagia group was significantly lower
      than the ones in the control group (P < 0.05). Conclusion. Menorrhagia has
      negative effects on women's quality of life. Therefore, quality of life of the
      women consulting the clinics with menorrhagia complaint should be investigated
      and effective approaches should be designed. 

PMID- 23970972
TI  - Liver injury induced by anticancer chemotherapy and radiation therapy.
AB  - Cytotoxic chemotherapy prolongs survival of patients with advanced and metastatic
      tumors. This is, however, a double-edged sword with many adverse effects. Since
      the liver has a rich blood supply and plays an active role in the metabolism of
      medications, it is not surprising that there can be hepatic injury related to
      chemotherapy. In addition, radioembolization may affect the parenchyma of normal
      and cirrhotic livers. We review chemotherapy-associated liver injury in patients
      with colorectal liver metastases, including downsizing chemotherapy and
      neoadjuvant chemotherapy. We discuss the mechanism of the hepatic injury,
      secondary to reactive oxygen species, and the spectrum of hepatic injury
      including, steatosis, steatohepatitis, hepatic sinusoidal injury and highlight
      the pharmacogenomics of such liver insults. Methods for reducing and treating the
      hepatotoxicity are discussed for specific agents including tamxifen and the newly
      introduced targeted antibodies. 

PMID- 23970974
TI  - Anti-Inflammatory Effects of Hyptis albida Chloroform Extract on
      Lipopolysaccharide-Stimulated Peritoneal Macrophages.
AB  - We examined the effects of a chloroform extract of Hyptis albida (CHA) on
      inflammatory responses in mouse lipopolysaccharide (LPS) induced peritoneal
      macrophages. Our findings indicate that CHA inhibits LPS-induced production of
      tumor necrosis factor (TNF- alpha ) and interleukin-6 (IL-6). During the process,
      levels of cyclooxygenase-2 (COX-2), nitric oxide synthase (iNOS), and nitric
      oxide (NO) increased in the mouse peritoneal macrophages; however, the extract
      suppressed them significantly. These results provide novel insights into the anti
      inflammatory actions of CHA and support its potential use in the treatment of
      inflammatory diseases. 

PMID- 23970975
TI  - Oral janus kinase inhibitor for the treatment of rheumatoid arthritis:
      tofacitinib.
AB  - Since the introduction of immune modulators in the treatment of rheumatoid
      arthritis (RA), there has been hope that orally effective biologic agents would
      be developed. Tofacitinib, a Janus kinase inhibitor, has become the first oral
      biologic to receive approval for use in active RA patients. This paper reviews
      the efficacy and safety profile of Tofacitinib at dosages of 5 mg and 10 mg twice
      daily. Remarkable improvement in terms of ACR 20 response and HAQ-DI score was
      noted at month 3 and month 6. DAS 28-4 ESR < 2.6 achievement was noticeably
      obvious at month 6 for both dosages. No significant serious adverse events,
      serious infections, neutropenia, or anaemia were observed compared to placebo. In
      fact, Tofacitinib 5 mg was even found to have significant protective effect of
      anaemia in the meta-analysis (P = 0.004). Tofacitinib has a noticeable efficacy
      in controlling disease activity in RA with a manageable safety profile. However,
      longer studies are needed for its long-term safety profile. 

PMID- 23970976
TI  - Laryngeal Aerodynamics in Children with Hearing Impairment versus Age and Height
      Matched Normal Hearing Peers.
AB  - Lack of proper auditory feedback in hearing-impaired subjects results in
      functional voice disorder. It is directly related to discoordination of intrinsic
      and extrinsic laryngeal muscles and disturbed contraction and relaxation of
      antagonistic muscles. A total of twenty children in the age range of 5-10 years
      were considered for the study. They were divided into two groups: normal hearing
      children and hearing aid user children. Results showed a significant difference
      in the vital capacity, maximum sustained phonation, and fast adduction abduction
      rate having equal variance for normal and hearing aid user children,
      respectively, but no significant difference was found in the peak flow value with
      being statistically significant. A reduced vital capacity in hearing aid user
      children suggests a limited use of the lung volume for speech production. It may
      be inferred from the study that the hearing aid user children have poor vocal
      proficiency which is reflected in their voice. The use of voicing component in
      hearing impaired subjects is seen due to improper auditory feedback. It was found
      that there was a significant difference in the vital capacity, maximum sustained
      phonation (MSP), and fast adduction abduction rate and no significant difference
      in the peak flow. 

PMID- 23970978
TI  - Impact of arsenic toxicity on black gram and its amelioration using phosphate.
AB  - The toxicity of arsenic in soil and ground water is one of the most important
      environmental problems particularly in South-East Asia. Arsenic-polluted
      irrigation water creates hazard in soil environment and also in crop quality. In
      the present study, response of black gram (Vigna mungo L.) to arsenic with or
      without phosphate application was investigated. Arsenic-treated plants showed
      reduction in their growth and pigment content. Arsenic significantly enhanced
      lipid peroxidation, electrolyte leakage, and level of proline showing oxidative
      stress. Arsenic toxicity was associated with an increase in the activities of
      antioxidative enzymes like superoxide dismutase, peroxidase, and ascorbate
      peroxidase whereas catalase activity decreased at higher arsenic dose. Joint
      application of phosphate with arsenic resulted in significant alterations in most
      of the parameters tested under the purview of arsenic treatment alone which lead
      to better growth in black gram. 

PMID- 23970979
TI  - Dual lesions: a diagnostic dilemma.
AB  - Glandular odontogenic cyst (GOC) is a rare aggressive developmental cyst of the
      jaw. It most commonly occurs in middle-aged people with mandible anterior region
      being the most affected site. This lesion can present as a unilocular or
      multilocular radiolucency and has high recurrence rate. The histopathologic
      features of the GOC are complex and often coincide with the features of
      dentigerous cyst, radicular cyst, and low-grade central mucoepidermoid carcinoma
      (CMEC). At times, the microscopic features are so similar to central low-grade
      mucoepidermoid carcinoma that it becomes highly impossible to distinguish the two
      entities even with various advanced investigations. The reported case represents
      one such diagnostic dilemma occurring in the maxilla which is a rare site, and
      the lesion/s appeared as two distinct entities, that is, GOC and CMEC on either
      aspects of the same side of maxilla clinically, yet showing continuity on
      advanced imaging and demonstrating histopathological perplexity. 

PMID- 23970977
TI  - Environment, leptin sensitivity, and hypothalamic plasticity.
AB  - Regulation of feeding behavior has been a crucial step in the interplay between
      leptin and the arcuate nucleus of the hypothalamus (ARC). On one hand, the basic
      mechanisms regulating central and peripheral action of leptin are becoming
      increasingly clear. On the other hand, knowledge on how brain sensitivity to
      leptin can be modulated is only beginning to accumulate. This point is of
      paramount importance if one considers that pathologically obese subjects have
      high levels of plasmatic leptin. A possible strategy for exploring neural
      plasticity in the ARC is to act on environmental stimuli. This can be achieved
      with various protocols, namely, physical exercise, high-fat diet, caloric
      restriction, and environmental enrichment. Use of these protocols can, in turn,
      be exploited to isolate key molecules with translational potential. In the
      present review, we summarize present knowledge about the mechanisms of plasticity
      induced by the environment in the ARC. In addition, we also address the role of
      leptin in extrahypothalamic plasticity, in order to propose an integrated view of
      how a single diffusible factor can regulate diverse brain functions. 

PMID- 23970980
TI  - Mucoepidermoid carcinoma in a minor salivary gland in a child.
AB  - Mucoepidermoid carcinoma (MEC), one of the most common salivary gland
      malignancies, is rare in children. MEC mainly occurs in the parotid gland, along
      with minor glands being the second common site, particularly in palate. Clinical,
      histological, and radiological findings of palatal MEC in a 12-year-old girl are
      presented with three-year follow-up. Pathologic lesions must be considered in
      differential diagnoses of intraoral asymptomatic lesions, and their detailed
      inspection should be taken into consideration. 

PMID- 23970981
TI  - An isolated bee sting involving multiple cranial nerves.
AB  - Hymenoptera stings are self-limiting events or due to allergic reactions.
      Sometimes envenomation with Hymenoptera can cause rare complications such as
      acute encephalopathy, peripheral neuritis, acute renal failure, nephrotic
      syndrome, silent myocardial infarction, rhabdomyolysis, conjunctivitis, corneal
      infiltration, lens subluxation, and optic neuropathy. The mechanism of peripheral
      nervous system damage is not clearly known. In our studied case after bee sting
      on face between the eyebrows with little erythema and 1 * 1 cm in size, bilateral
      blindness developed and gradually improved. Lateral movement of eyes was
      restricted with no pain. Involvement of cranial nerves including II, V, and VI
      was found. With conservative therapy after a year significant improvement has
      been achieved. 

PMID- 23970982
TI  - Celiac disease presenting as Fever of unknown origin.
AB  - Celiac disease (CD) is a common autoimmune enteropathy that occurs, in affected
      individuals, with exposure to gluten in the diet and improves with removal of
      dietary gluten. Although CD is readily considered in patients with classical
      presentations of the disease, atypical manifestations may be the only presenting
      symptoms. We present a case of CD in a 16-year-old female presenting as fever of
      unknown origin, which has not been reported previously. The postulated mechanism
      for fever in CD and the importance of clinicians having a low threshold for
      considering CD in the differential diagnosis of fever of unknown origin and other
      enigmatic clinical presentations is discussed. 

PMID- 23970983
TI  - Nonfamilial, MPL S505N-Mutated Essential Thrombocythaemia.
AB  - Mutations of MPL are present in a significant proportion of patients with the
      myeloproliferative neoplasms (MPN), primary myelofibrosis (PMF), and essential
      thrombocythaemia (ET). The most frequent of these mutations, W515L and W515K,
      occur in exon 10 of MPL, which encodes the receptor for thrombopoietin. Another
      exon 10 mutation, MPL S505N, has been shown to be a founder mutation in several
      pedigrees with familial thrombocythaemia where it is associated with a high
      thrombotic risk, splenomegaly and progression to bone marrow fibrosis. Rare cases
      of sporadic, nonfamilial, MPL S505N MPN have been documented, but the presenting
      laboratory and clinical features have not been described in detail. The diagnosis
      and clinical course of a case of MPL S505N-positive MPN are presented with
      diagnostic features and treatment response resembling typical ET but with
      evidence of increasing bone marrow fibrosis. Further MPN cases possessing this
      genotype require reporting in order to ascertain whether any particular
      morphological or clinical features, if present, determine clinical course and aid
      the refinement of therapeutic options. 

PMID- 23970984
TI  - Pseudomyopathic changes in needle electromyography in lambert-eaton myasthenic
      syndrome.
AB  - Lambert-Eaton myasthenic syndrome (LEMS) is a rare presynaptic disorder of the
      neuromuscular junction in association with cancer and subsequently in cases in
      which no neoplasm has been detected (O'Neill et al., 1988). The diagnosis of LEMS
      is based on the combination of fluctuating muscle weakness, diminished or absent
      reflexes, and a more than 60% increment of compound muscle action potential
      (CMAP) amplitude after brief exercise or 50 Hz stimulation for 1 s in a
      repetitive nerve stimulation (RNS) test (Oh et al., 2005). On the other hand,
      needle electromyography (EMG) findings related to LEMS have not been well
      described. Here, we report a case of LEMS, which showed apparent myopathic
      changes in needle EMG findings. Furthermore, we retrospectively examined the
      needle EMG findings in 8 patients with LEMS. In six of the 8 patients, the EMG
      findings showed myopathy-like findings. Although the findings of needle EMG
      indicated myopathic changes at a glance, the motor unit potential (MUP) returned
      to normal after a sustained strong muscle contraction. We propose the name
      "pseudomyopathic changes" for this phenomenon. 

PMID- 23970985
TI  - Vaginal primary malignant melanoma: a rare and aggressive tumor.
AB  - Vaginal primary malignant melanoma is a rare and very aggressive tumor. It most
      commonly occurs in postmenopausal women, with a mean age of 57 years. Our patient
      is an 80-year-old, postmenopausal Greek woman presented with a complaint of
      abnormal vaginal bleeding. On gynecologic examination there was a pigmented,
      raised, ulcerated, and irregular lesion 5 * 4.5 cm in the upper third of anterior
      vaginal wall. She underwent a wide local excision of the lesion. The
      histopathology revealed vaginal primary malignant melanoma with ulceration and no
      clear surgical margins. She denied any additional surgical interventions and
      underwent to postoperative adjuvant radiotherapy. Follow up 5 months after
      initial diagnosis revealed no evidence of local recurrence or distant metastasis.
      The prognosis of vaginal primary malignant melanoma is very poor despite
      treatment modality, because most of the cases are diagnosed at advanced stage.
      Particularly patients with no clear surgical margins and tumor size >3 cm needed
      postoperative adjuvant radiotherapy. 

PMID- 23970986
TI  - Confocal microscopy in biopsy proven argyrosis.
AB  - Purpose. To evaluate the confocal microscopy findings of a 46-year-old male with
      bilateral biopsy proven argyrosis. Materials and Methods. Besides routine
      ophthalmologic examination, anterior segment photography and confocal microscopy
      with cornea Rostoch module attached to HRT II (Heidelberg Engineering GmbH,
      Heidelberg, Germany) were performed. Findings. Squamous metaplastic changes on
      conjunctival epithelium and intense highly reflective extracellular punctiform
      deposits in conjunctival substantia propria were detected. Corneal epithelium was
      normal. Highly reflective punctiform deposits starting from anterior to mid
      stroma and increasing through Descemet's membrane were evident. Corneal
      endothelium could not be evaluated due to intense stromal deposits. Conclusion.
      Confocal microscopy not only supports diagnosis in ocular argyrosis, but also
      demonstrates the intensity of the deposition in these patients. 

PMID- 23970987
TI  - Anterolateral Corrective Lumbar Corpectomy and Interbody Fusion by Using Extended
      Screw Fixation without Posterior Instrumentation for Posttraumatic Kyphosis.
AB  - A 26-year-old paraplegic schizophrenic Japanese woman suffered from severe
      kyphosis and back pain derived from lumbar burst fractures caused by jumping. She
      had already undergone resection of the L1 and L2 spinous processes for sharp
      angular kyphosis, but she still had severe kyphosis and back pain at the L1 and
      L2. Radiographical examination revealed fused anterior columns at L1 and L2 with
      severe local kyphosis and a significantly decreased percutaneous distance in the
      back. The patient underwent anterior instrumented bony resection including an L2
      vertebral osteotomy: bilateral L2-L3 facetectomy and partial posterior osteotomy
      of the L2 vertebrae via a posterior approach followed by an anterior corpectomy
      of the L2 vertebrae and insertion of a cylindrical cage. No posterior
      instrumentation was used owing to the presence of atrophied paraspinal soft
      tissues. Lumbar interbody fusion was performed with vertebral body screws
      extending from T12 to L4 and corresponding anterior distension and posterior
      compression. The procedure corrected the kyphosis by 15 degrees  and enhanced
      local stability. Postsurgical visual analogue scale improved from 9.0 to 2.0 and
      Oswestry Disability Index from 40 to 17.8, respectively. In conclusion, we have
      demonstrated that anterolateral interbody fusion using extended fixation can
      compensate for posterior corrective surgery. 

PMID- 23970988
TI  - An unusual case of pleuropulmonary blastoma in a child with jejunal hamartomas.
AB  - We report a rare case of 9-month-old girl who presented with a choking episode
      and was found to have an incidental finding of a lung cyst and iron deficiency
      anemia leading to the diagnosis of pleuropulmonary blastoma (PPB) and a jejunal
      hamartoma. Our patient is the eighth that has been reported with the association
      of PPB with jejunal hamartoma and the first one in the radiological literature.
      PPB is the pulmonary analog of other dysontogenetic neoplasms in childhood. A
      biological sequence has been described with the three types of PPB to be
      interrelated as part of pathologic progression. PPB can be associated with other
      cysts and/or neoplasms in different organs. PPB is part of a hereditary neoplasia
      predisposition syndrome in up to 40% of cases. Mutations in DICER gene have been
      described with PPB. Hence, a pediatric patient diagnosed with PPB should be
      screened for associated conditions during childhood and adolescence including
      intestinal polyps. Obtaining family history for other neoplasms or cysts is
      important information that should raise the possibility of PPB in pediatric
      patients with cystic lung lesions. The presence of this syndrome should alert the
      clinician to screen and follow up patients and their relatives. 

PMID- 23970989
TI  - Hemophagocytic Syndrome Associated with Mycoplasma pneumoniae Pneumonia.
AB  - Mycoplasma pneumoniae (Mp) sometimes causes immunological complications in
      children. We present a rare case of hemophagocytic syndrome (HPS) caused by Mp in
      a previously healthy 7-year-old Japanese girl. A chest radiograph obtained to
      evaluate the source of her fever showed infiltration in the lower right lung with
      mild splenomegaly. We could diagnose the patient with HPS on the basis of the
      hemophagocytic-lymphohistiocytosis- (HLH) 2004 criteria. She met the criteria for
      fever, splenomegaly, neutrophil count (<1,000/ MU L), platelet count (<10.0 *
      10(4)/ MU L), fasting triglyceride level (>265 mg/dL), and ferritin level (>500
      ng/mL). Furthermore, a peripheral blood smear showed an increased number of
      monocytes/macrophages with erythrophagocytosis. Treatment with clarithromycin and
      prednisolone, which was initiated soon after the diagnosis, was successful. Mp
      infection might partly progress to HPS in certain conditions. Clinicians should
      be aware of HPS caused by Mp and start appropriate treatment as soon as possible
      if the disease is suspected. 

PMID- 23970990
TI  - Malignant Peripheral Nerve Sheath Tumour: CT and MRI Findings.
AB  - Malignant peripheral nerve sheath tumour (MPNST) is extremely rare malignancy in
      the general population, occurring more frequently in patients with
      Neurofibromatosis type 1 (NF1). In the literature five cases of MPNST arising
      from the parapharyngeal space (PPS) in patients without neurofibromatosis have
      been reported. We report imaging techniques in a patient with MPNST in the PPS,
      who had neither a family history nor sign of NF1. Computed tomography (CT) scan
      and magnetic resonance imaging (MRI) were performed for a correct therapeutic
      planning. CT and MRI findings were correlated with hystopathological diagnosis. 

PMID- 23970991
TI  - A Rare Side Effect due to TNF-Alpha Blocking Agent: Acute Pleuropericarditis with
      Adalimumab.
AB  - Tumor necrosis factor-alpha antagonism is an important treatment strategy in
      patients with rheumatoid arthritis, psoriatic arthritis, vasculitis, and
      ankylosing spondylitis. Adalimumab is one of the well-known tumor necrosis factor
      alpha blocking agents. There are several side effects reported in patients with
      adalimumab therapy. Cardiac side effects of adalimumab are rare. Only a few
      cardiac side effects were reported. A 61-year-old man treated with adalimumab for
      the last 6 months due to psoriatic arthritis presented with typically acute
      pleuropericarditis. Chest X-ray and echocardiography demonstrated marked
      pericardial effusion. Patient was successfully evaluated for the etiology of
      acute pleuro-pericarditis. Every etiology was excluded except the usage of
      adalimumab. Adalimumab was discontinued, and patient was treated with 1200 mg of
      ibuprofen daily. Control chest X-ray and echocardiography after three weeks
      demonstrated complete resolution of both pleural and pericardial effusions. This
      case clearly demonstrated the acute onset of pericarditis with adalimumab usage.
      Acute pericarditis and pericardial effusion should be kept in mind in patients
      with adalimumab treatment. 

PMID- 23970992
TI  - Gallstone ileus of the colon: leave no stone unturned.
AB  - A case of gallstone ileus of the colon with illustrative pictures is presented,
      making the physicians more aware of this rare entity. Furthermore, the use of
      imaging modalities for diagnosis and decision making in management strategy is
      discussed. 

PMID- 23970993
TI  - Inferior epigastric artery pseudoaneurysm in a kidney transplant recipient.
AB  - Pseudoaneurysm of inferior epigastric artery (IEA) is a very rare clinical
      entity. We reported a case of combined kidney transplant and pseudoaneurysmectomy
      in a young HBV-HCV-HIV recipient. This case emphasizes the possibility of
      planning a safe and correct surgical treatment and the best timing to treat IEA
      pseudoaneurysm. An exhaustive preoperative radiological study in all patients
      candidate to kidney transplant could identify the possible aortoiliac disease
      both stenotic or dilatative even if it is rare and helps to define the best
      treatment options. 

PMID- 23970994
TI  - Varicocele and a vascular tumor in the testis.
AB  - A 50-year-old man presented a rare morphological constellation: a left-sided
      varicocele (stage 3) and a vascular rich Sertoli cell tumor. 

PMID- 23970996
TI  - Preoperative white blood cell count and risk of 30-day readmission after cardiac
      surgery.
AB  - Approximately 1 in 5 patients undergoing cardiac surgery are readmitted within 30
      days of discharge. Among the primary causes of readmission are infection and
      disease states susceptible to the inflammatory cascade, such as diabetes, chronic
      obstructive pulmonary disease, and gastrointestinal complications. Currently, it
      is not known if a patient's baseline inflammatory state measured by crude white
      blood cell (WBC) counts could predict 30-day readmission. We collected data from
      2,176 consecutive patients who underwent cardiac surgery at seven hospitals.
      Patient readmission data was abstracted from each hospital. The independent
      association with preoperative WBC count was determined using logistic regression.
      There were 259 patients readmitted within 30 days, with a median time of
      readmission of 9 days (IQR 4-16). Patients with elevated WBC count at baseline
      (10,000-12,000 and >12,000 mm(3)) had higher 30-day readmission than those with
      lower levels of WBC count prior to surgery (15% and 18% compared to 10%-12%, P =
      0.037). Adjusted odds ratios were 1.42 (0.86, 2.34) for WBC counts 10,000-12,000
      and 1.81 (1.03, 3.17) for WBC count > 12,000. We conclude that WBC count measured
      prior to cardiac surgery as a measure of the patient's inflammatory state could
      aid clinicians and continuity of care management teams in identifying patients at
      heightened risk of 30-day readmission after discharge from cardiac surgery. 

PMID- 23970997
TI  - Does percutaneous kyphoplasty have better functional outcome than vertebroplasty
      in single level osteoporotic compression fractures? A comparative prospective
      study.
AB  - Purpose. To evaluate the relative differences in surgical outcome of kyphoplasty
      (KP) versus vertebroplasty (VP) in the patients with single level refractory
      osteoporotic compression fractures (OCFs). Method. From August 2008 to May 2012,
      we intermittently treated 57 patients with single level OCF by PV and KP (Groups
      A and B, resp.). We used visual analogue scale (VAS) and short form 36 (SF36)
      questionnaire to measure functional recovery and followed them for six months.
      Independent samples t- and Kendall's tau-b tests were for statistics. Results. In
      terms of age, number, and bone mineral density of the patients, there were no
      significant differences between the two groups. In both groups, VAS and SF-36
      scores improved significantly and remained relatively stable throughout the
      follow-up period. We had 9 and 6 asymptomatic cement extravasations and 5 and 8
      new vertebral fractures in Group A and B, respectively. In comparing the two
      groups, the results indicated that KP almost failed to show any significant
      higher effect relative to VP during this period. Conclusions. In considering the
      high cost of KP relative to VP in the developing countries like Iran, there is no
      logical reason to use KP in a single level refractory OCF in these regions. 

PMID- 23970998
TI  - A naturally occurring feline model of head and neck squamous cell carcinoma.
AB  - Despite advances in understanding cancer at the molecular level, timely and
      effective translation to clinical application of novel therapeutics in human
      cancer patients is lacking. Cancer drug failure is often a result of toxicity or
      inefficacy not predicted by preclinical models, emphasizing the need for
      alternative animal tumor models with improved biologic relevancy. Companion
      animals (dogs and cats) provide an opportunity to capitalize on an underutilized
      and biologically relevant translational research model which allows spontaneous
      disease modeling of human cancer. Head and neck squamous cell carcinoma (HNSCC)
      is a common cancer with a poor prognosis and limited clinical advancements in
      recent years. One potential novel spontaneous animal tumor model is feline oral
      squamous cell carcinoma (FOSCC). FOSCC and HNSCC share similar etiopathogenesis
      (tobacco and papillomavirus exposure) and molecular markers (EGFR, VEGF, and
      p53). Both human and feline SCCs share similar tumor biology, clinical outcome,
      treatment, and prognosis. Future clinical trials utilizing FOSCC as a tumor model
      may facilitate translation of preclinical cancer research for human cancer
      patients. 

PMID- 23970999
TI  - Acute stroke imaging: recent updates.
AB  - Acute ischemic stroke imaging is one of the leading causes of death and
      disability worldwide. Neuroimaging plays a crucial role in early diagnosis and
      yields essential information regarding tissue integrity, a factor that remains a
      key therapeutic determinant. Given the widespread public health implications of
      stroke and central role of neuroimaging in overall management, acute stroke
      imaging remains a heavily debated, extensively researched, and rapidly evolving
      subject. There has been recent debate in the scientific community due to divided
      opinions on the use of CT perfusion and access-related limitations of MRI. In
      this paper we review and summarize recent updates relevant to acute stroke
      imaging and propose an imaging paradigm based on the recently available evidence.

PMID- 23970995
TI  - Ankylosing spondylitis: from cells to genes.
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown
      etiology, though it is considered an autoimmune disease. HLA-B27 is the risk
      factor most often associated with AS, and although the mechanism of involvement
      is unclear, the subtypes and other features of the relationship between HLA-B27
      and AS have been studied for years. Additionally, the key role of IL-17 and Th17
      cells in autoimmunity and inflammation suggests that the latter and the cytokines
      involved in their generation could play a role in the pathogenesis of this
      disease. Recent studies have described the sources of IL-17 and IL-23, as well as
      the characterization of Th17 cells in autoimmune diseases. Other cells, such as
      NK and regulatory T cells, have been implicated in autoimmunity and have been
      evaluated to ascertain their possible role in AS. Moreover, several
      polymorphisms, mutations and deletions in the regulatory proteins, protein-coding
      regions, and promoter regions of different genes involved in immune responses
      have been discovered and evaluated for possible genetic linkages to AS. In this
      review, we analyze the features of HLA-B27 and the suggested mechanisms of its
      involvement in AS while also focusing on the characterization of the immune
      response and the identification of genes associated with AS. 

PMID- 23971000
TI  - Histopathological studies on stunting syndrome in broilers, lahore, pakistan.
AB  - Runting stunting syndrome (RSS) is a multifactorial disease with many names and
      faces that had caused considerable economic losses to poultry through reduced
      uniformity, reduced livability, decreased body weights, elevated feed
      conversions, and many secondary diseases. The aim of the current study was to
      evaluate the effect of stunting syndrome on histopathology in chicks (n = 120) of
      different ages collected from nine different farms. Grouping was done on the
      basis of age (G1 = 1-10 days, G2 = 11-20 days, G3 = 21-30 days, and G4 = 31-40
      days) including both stunted and normal chicks. Histopathological findings were
      the intestinal lesions (29%), including degeneration of villi, crypts, epithelial
      cells and lamina propria. Pancreatic histopathological lesions (16.65%) included
      the fibrosis, vacuolation, and degeneration of acinar cells. Degeneration of
      follicles and epithelial cells, of bursa of fabricius (43%) and dilation of
      glandular cells of proventriculus including lymphocytes infiltration (5.6%) were
      other histopathological findings. All these changes may interfere with normal
      digestive processes and normal body functioning resulting in poor weight gain and
      retarded growth or stunting of chicks. 

PMID- 23971001
TI  - Simultaneous Determination of Matrine and Tinidazole in Compound Lotion by RH
      HPLC Method.
AB  - A simple, sensitive, and accurate RP-HPLC coupled with UV detector method was
      developed and validated for simultaneous determination of matrine and tinidazole
      in compound lotion. The chromatographic separation of the two compounds was
      carried out with a SinoChoom ODS-BP C18 column (5  MU m, 4.6 mm * 200 mm)
      analytical column, using a mobile phase consisting of 0.025 mol/L potassium
      dihydrogen phosphate (containing triethylamine 0.05%, v/v) and acetonitrile (80 :
      20, v/v) at a flow rate of 1.0 mL/min. The detection was monitored at 210 and 310
      nm for matrine and tinidazole, respectively. Total run time was 12 min, and the
      column was maintained at 25 degrees C. The excipients in the compound lotion did
      not interfere with the drug peaks. The calibration curves of matrine and
      tinidazole were fairly linear over the concentration ranges of 10.0-100.0  MU
      g/mL (r = 0.9954) and 20.0-200.0  MU g/mL (r = 0.9968), respectively. The RSD of
      both the intraday and interday variations was below 1.5% for matrine and
      tinidazole. The proposed HPLC method was validated according to International
      Conference on Harmonisation and proved to be suitable for the simultaneous
      determination of matrine and tinidazole in compound lotion. 

PMID- 23971002
TI  - Portable bioactive paper-based sensor for quantification of pesticides.
AB  - A paper-based biosensor was developed for the detection of the degradation
      products of organophosphorus pesticides. The biosensor quantifies acetylcholine
      esterase inhibitors in a fast, disposable, cheap, and accurate format. We
      specifically focused on the use of sugar or protein stabilizer to achieve a
      biosensor with long shelf-life. The new biosensor detected malathion with a
      detection limit of 2.5 ppm in 5 min incubation time. The operational stability
      was confirmed by testing 60 days storage at 4 degrees C when glucose was used as
      stabilizer. 

PMID- 23971003
TI  - How are countries in the Western Pacific Region tracking the HIV epidemic?
      Results from a 2011 survey of ministries of health.
AB  - In 2011, as part of the World Health Organization global reporting tool to
      collect data on the progress of improving the health sector response to HIV/AIDS
      towards universal access, a questionnaire was sent to ministries of health of
      Western Pacific Region Member States on the scope and functioning of their HIV
      surveillance systems. Of the 17 countries that responded, 13 were low- to middle
      income countries and four were high-income countries. Regular serosurveillance
      surveys are conducted with female sex workers in all lower- and middle-income
      countries that responded to the survey but less so with people who inject drugs
      and men who have sex with men. Furthermore, there are no surveillance activities
      of the key populations in most of the Pacific island countries. It is recommended
      that estimations of high-risk populations be conducted in priority Pacific island
      countries and tailored surveillance systems be designed. Efforts should also be
      made to gather and accumulate data from sufficient geographic coverage to allow
      the HIV epidemic to continue to be monitored. 

PMID- 23971005
TI  - A proposal for a targeted screening program for renal cancer.

PMID- 23971006
TI  - Five fraction image-guided radiosurgery for primary and recurrent meningiomas.
AB  - PURPOSE: Benign tumors that arise from the meninges can be difficult to treat due
      to their potentially large size and proximity to critical structures such as
      cranial nerves and sinuses. Single fraction radiosurgery may increase the risk of
      symptomatic peritumoral edema. In this study, we report our results on the
      efficacy and safety of five fraction image-guided radiosurgery for benign
      meningiomas. MATERIALS/METHODS: Clinical and radiographic data from 38 patients
      treated with five fraction radiosurgery were reviewed retrospectively. Mean tumor
      volume was 3.83 mm(3) (range, 1.08-20.79 mm(3)). Radiation was delivered using
      the CyberKnife, a frameless robotic image-guided radiosurgery system with a
      median total dose of 25 Gy (range, 25-35 Gy). RESULTS: The median follow-up was
      20 months. Acute toxicity was minimal with eight patients (21%) requiring a short
      course of steroids for headache at the end of treatment. Pre-treatment
      neurological symptoms were present in 24 patients (63.2%). Post treatment,
      neurological symptoms resolved completely in 14 patients (58.3%), and were
      persistent in eight patients (33.3%). There were no local failures, 24 tumors
      remained stable (64%) and 14 regressed (36%). Pre-treatment peritumoral edema was
      observed in five patients (13.2%). Post-treatment asymptomatic peritumoral edema
      developed in five additional patients (13.2%). On multivariate analysis, pre
      treatment peritumoral edema and location adjacent to a large vein were
      significant risk factors for radiographic post-treatment edema (p = 0.001 and p =
      0.026 respectively). CONCLUSION: These results suggest that five fraction image
      guided radiosurgery is well tolerated with a response rate for neurologic
      symptoms that is similar to other standard treatment options. Rates of
      peritumoral edema and new cranial nerve deficits following five fraction
      radiosurgery were low. Longer follow-up is required to validate the safety and
      long-term effectiveness of this treatment approach.

PMID- 23971004
TI  - Venus Flytrap (Dionaea muscipula Solander ex Ellis) Contains Powerful Compounds
      that Prevent and Cure Cancer.
AB  - Chemoprevention uses natural or synthetic molecules without toxic effects to
      prevent and/or block emergence and development of diseases including cancer. Many
      of these natural molecules modulate mitogenic signals involved in cell survival,
      apoptosis, cell cycle regulation, angiogenesis, or on processes involved in the
      development of metastases occur naturally, especially in fruits and vegetables
      bur also in non-comestible plants. Carnivorous plants including the Venus flytrap
      (Dionaea muscipula Solander ex Ellis) are much less investigated, but appear to
      contain a wealth of potent bioactive secondary metabolites. Aim of this review is
      to give insight into molecular mechanisms triggered by compounds isolated from
      these interesting plants with either therapeutic or chemopreventive potential. 

PMID- 23971007
TI  - Influence of laboratory animal hosts on the life cycle of Hyalomma marginatum and
      implications for an in vivo transmission model for Crimean-Congo hemorrhagic
      fever virus.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the most geographically
      widespread arboviruses and causes a severe hemorrhagic syndrome in humans. The
      virus circulates in nature in a vertebrate-tick cycle and ticks of the genus
      Hyalomma are the main vectors and reservoirs. Although the tick vector plays a
      central role in the maintenance and transmission of CCHFV in nature,
      comparatively little is known of CCHFV-tick interactions. This is mostly due to
      the fact that establishing tick colonies is laborious, and working with CCHFV
      requires a biosafety level 4 laboratory (BSL4) in many countries. Nonetheless, an
      in vivo transmission model is essential to understand the epidemiology of the
      transmission cycle of CCHFV. In addition, important parameters such as vectorial
      capacity of tick species, levels of infection in the host necessary to infect the
      tick, and aspects of virus transmission by tick bite including the influence of
      tick saliva, cannot be investigated any other way. Here, we evaluate the
      influence of different laboratory animal species as hosts supporting the life
      cycle of Hyalomma marginatum, a two-host tick. Rabbits were considered the host
      of choice for the maintenance of the uninfected colonies due to high larval
      attachment rates, shorter larval-nymphal feeding times, higher nymphal molting
      rates, high egg hatching rates, and higher conversion efficiency index (CEI).
      Furthermore, we describe the successful establishment of an in vivo transmission
      model for CCHFV in a BSL4 biocontainment setting using interferon knockout mice.
      This will give us a new tool to study the transmission and interaction of CCHFV
      with its tick vector. 

PMID- 23971010
TI  - Discovering unique tobacco use patterns among Alaska Native people.
AB  - BACKGROUND: Alaska Native people are disproportionately impacted by tobacco
      related diseases in comparison to non-Native Alaskans. DESIGN: We used Alaska's
      Behavioral Risk Factor Surveillance System (BRFSS) to describe tobacco use among
      more than 4,100 Alaska Native adults, stratified by geographic region and
      demographic groups. RESULTS: Overall tobacco use was high: approximately 2 out of
      every 5 Alaska Native adults reported smoking cigarettes (41.2%) and 1 in 10
      reported using smokeless tobacco (SLT, 12.3%). A small percentage overall (4.8%)
      reported using iq'mik, an SLT variant unique to Alaska Native people. When
      examined by geographic region, cigarette smoking was highest in remote geographic
      regions; SLT use was highest in the southwest region of the state. Use of iq'mik
      was primarily confined to a specific area of the state; further analysis showed
      that 1 in 3 women currently used iq'mik in this region. CONCLUSION: Our results
      suggest that different types of tobacco use are epidemic among diverse Alaska
      Native communities. Our results also illustrate that detailed analysis within
      racial/ethnic groups can be useful for public health programme planning to reduce
      health disparities.

PMID- 23971011
TI  - The epidemiology of invasive pneumococcal disease in the Canadian North from 1999
      to 2010.
AB  - INTRODUCTION: The International Circumpolar Surveillance network is a population
      based surveillance system that collects data on invasive pneumococcal disease
      (IPD) in Northern Canada. A 7-valent pneumococcal conjugate vaccine was first
      introduced in some regions of Northern Canada in 2002, followed by 10-valent
      (2009) and 13-valent (PCV-13) vaccines (2010). A 23-valent polysaccharide (PPV
      23) vaccine was first introduced in 1988 for special populations and adults aged
      65 years and older. To describe the epidemiology in the context of pneumococcal
      vaccination programs, we analysed surveillance data from Northern Canada from
      1999 to 2010. METHODS: A standardized case report form capturing demographic and
      clinical information was completed for all IPD cases in Northern Canada meeting
      the national case definition. Isolates were sent to a reference laboratory for
      confirmation, serotyping and antimicrobial resistance testing. Both laboratory
      and epidemiological data were sent to the Public Health Agency of Canada for
      analysis. Population denominators were obtained from Statistics Canada. RESULTS:
      From 1999 to 2010, 433 IPD cases were reported (average 36 cases per year).
      Incidence was greatest among infants aged < 2 years and among those aged 65 years
      and older, with an average annual incidence of 133 and 67 cases per 100,000
      population, respectively. After a peak in incidence in 2008, rates among infants
      have declined. Incidence rates varied from 2 to 16 times greater, depending on
      the year, among Aboriginals compared to non-Aboriginals. Hospitalization was
      reported in 89% of all cases and the case fatality ratio was 6.0%. Clinical
      manifestations varied, with some patients reporting > 1 manifestation. Pneumonia
      was the most common (70%), followed by bacteremia/septicaemia (30%) and
      meningitis (8%). Approximately, 42% of cases aged < 2 years in 2009 and 2010 had
      serotypes covered by the PCV-13. In addition, the majority (89%) of serotypes
      isolated in cases aged 65 years and older were included in the PPV-23 vaccine.
      CONCLUSION: IPD continues to be a major cause of disease in Northern Canadian
      populations, with particularly high rates among infants and Aboriginals.
      Continued surveillance is needed to determine the impact of conjugate
      pneumococcal vaccine programs. Additional studies investigating factors that
      predispose infants and Aboriginal peoples would also be beneficial.

PMID- 23971008
TI  - Tick salivary compounds: their role in modulation of host defences and pathogen
      transmission.
AB  - Ticks require blood meal to complete development and reproduction.
      Multifunctional tick salivary glands play a pivotal role in tick feeding and
      transmission of pathogens. Tick salivary molecules injected into the host
      modulate host defence responses to the benefit of the feeding ticks. To colonize
      tick organs, tick-borne microorganisms must overcome several barriers, i.e., tick
      gut membrane, tick immunity, and moulting. Tick-borne pathogens co-evolved with
      their vectors and hosts and developed molecular adaptations to avoid adverse
      effects of tick and host defences. Large gaps exist in the knowledge of survival
      strategies of tick-borne microorganisms and on the molecular mechanisms of tick
      host-pathogen interactions. Prior to transmission to a host, the microorganisms
      penetrate and multiply in tick salivary glands. As soon as the tick is attached
      to a host, gene expression and production of salivary molecules is upregulated,
      primarily to facilitate feeding and avoid tick rejection by the host. Pathogens
      exploit tick salivary molecules for their survival and multiplication in the
      vector and transmission to and establishment in the hosts. Promotion of pathogen
      transmission by bioactive molecules in tick saliva was described as saliva
      assisted transmission (SAT). SAT candidates comprise compounds with anti
      haemostatic, anti-inflammatory and immunomodulatory functions, but the molecular
      mechanisms by which they mediate pathogen transmission are largely unknown. To
      date only a few tick salivary molecules associated with specific pathogen
      transmission have been identified and their functions partially elucidated.
      Advanced molecular techniques are applied in studying tick-host-pathogen
      interactions and provide information on expression of vector and pathogen genes
      during pathogen acquisition, establishment and transmission. Understanding the
      molecular events on the tick-host-pathogen interface may lead to development of
      new strategies to control tick-borne diseases. 

PMID- 23971012
TI  - Adapting online learning for Canada's Northern public health workforce.
AB  - BACKGROUND: Canada's North is a diverse, sparsely populated land, where
      inequalities and public health issues are evident, particularly for Aboriginal
      people. The Northern public health workforce is a unique mix of professional and
      paraprofessional workers. Few have formal public health education. From 2009 to
      2012, the Public Health Agency of Canada (PHAC) collaborated with a Northern
      Advisory Group to develop and implement a strategy to strengthen public health
      capacity in Canada's 3 northern territories. Access to relevant, effective
      continuing education was identified as a key issue. Challenges include diverse
      educational and cultural backgrounds of public health workers, geographical
      isolation and variable technological infrastructure across the north. METHODS:
      PHAC's Skills Online program offers Internet-based continuing education modules
      for public health professionals. In partnership with the Northern Advisory Group,
      PHAC conducted 3 pilots between 2008 and 2012 to assess the appropriateness of
      the Skills Online program for Northern/Aboriginal public health workers. Module
      content and delivery modalities were adapted for the pilots. Adaptations included
      adding Inuit and Northern public health examples and using video and
      teleconference discussions to augment the online self-study component. RESULTS:
      Findings from the pilots were informative and similar to those from previous
      Skills Online pilots with learners in developing countries. Online learning is
      effective in bridging the geographical barriers in remote locations.
      Incorporating content on Northern and Aboriginal health issues facilitates
      engagement in learning. Employer support facilitates the recruitment and
      retention of learners in an online program. Facilitator assets included
      experience as a public health professional from the north, and flexibility to use
      modified approaches to support and measure knowledge acquisition and application,
      especially for First Nations, Inuit and Metis learners. CONCLUSIONS: Results
      demonstrate that appropriate adaptations to online professional development can
      provide practical, accessible means for a wide range of Northern/Aboriginal
      public health workers to acquire core competencies for public health.

PMID- 23971009
TI  - PGE(2) suppression of innate immunity during mucosal bacterial infection.
AB  - Prostaglandin E2 (PGE2) is an important lipid mediator in inflammatory and immune
      responses during acute and chronic infections. Upon stimulation by various
      proinflammatory stimuli such as lipopolysaccharide (LPS), interleukin (IL)-1beta,
      and tumor necrosis factor (TNF)-alpha, PGE2 synthesis is upregulated by the
      expression of cyclooxygenases. Biologically active PGE2 is then able to signal
      through four primary receptors to elicit a response. PGE2 is a critical molecule
      that regulates the activation, maturation, migration, and cytokine secretion of
      several immune cells, particularly those involved in innate immunity such as
      macrophages, neutrophils, natural killer cells, and dendritic cells. Both Gram
      negative and Gram-positive bacteria can induce PGE2 synthesis to regulate immune
      responses during bacterial pathogenesis. This review will focus on PGE2 in innate
      immunity and how bacterial pathogens influence PGE2 production during enteric and
      pulmonary infections. The conserved ability of many bacterial pathogens to
      promote PGE2 responses during infection suggests a common signaling mechanism to
      deter protective pro-inflammatory immune responses. Inhibition of PGE2 production
      and signaling during infection may represent a therapeutic alternative to treat
      bacterial infections. Further study of the immunosuppressive effects of PGE2 on
      innate immunity will lead to a better understanding of potential therapeutic
      targets within the PGE2 pathway. 

PMID- 23971013
TI  - What is important in the surroundings in order to extend the healthy life period?
      A regional study of 19 older women in a northern part of Norway.
AB  - INTRODUCTION: Participating in a community with other retired individuals to
      increase life quality can be possible for the older persons. Cultural and
      ethnical background is important for their social identity. OBJECTIVE: To
      identify what the informants think is important in their surroundings in order to
      extend their healthy life period. STUDY DESIGN: A structured questionnaire
      developed by the OCIN network. METHODS: Nineteen elderly women aged 75 years or
      more were interviewed. This regional survey is a pilot study in Norway. The data
      were collected during 2 periods, in 2009 and 2010. The data are analyzed using a
      result scheme prepared by the network OCIN. RESULTS: Our findings show that this
      is a group of elderly women that are concerned with promoting their own health.
      The participants wish to take care of themselves, so they do not become a burden
      for society and the local authorities. CONCLUSIONS: The findings of this study
      suggest that participation in the local context is important for promoting health
      and well-being among elderly in all ethnicities. For the Sami elderly, this is
      particularly important because meeting equal-minded people helps them maintain
      their Sami identity. In the Sami culture and among the Sami elderly, it is
      important to be "strong" and "healthy". Due to these norms, the elderly Sami
      women try to live with their illnesses and are less eager to go to the doctor
      when they are seriously ill.

PMID- 23971014
TI  - Renewable energy and sustainable communities: Alaska's wind generator experience.
AB  - BACKGROUND: In 1984, the Alaska Department of Commerce and Economic Development
      (DCED) issued the State's first inventory/economic assessment of wind generators,
      documenting installed wind generator capacity and the economics of replacing
      diesel-fuel-generated electricity. Alaska's wind generation capacity had grown
      from hundreds of installed kilowatts to over 15.3 megawatts (MW) by January 2012.
      METHOD: This article reviews data and conclusions presented in "Alaska's Wind
      Energy Systems; Inventory and Economic Assessment" (1). (Alaska Department of
      Commerce and Economic Development, S. Konkel, 1984). It provides a foundation and
      baseline for understanding the development of this renewable energy source.
      RESULTS: Today's technologies have evolved at an astonishing pace; a typical
      generator in an Alaska wind farm now is likely rated at 1.5-MW capacity, compared
      to the single-kilowatt (kW) machines present in 1984. Installed capacity has
      mushroomed, illustrated by Unalakleet's 600-kW wind farm dwarfing the original
      three 10-kW machines included in the 1984 inventory. Kodiak Electric had three
      1.5-MW turbines installed at Pillar Mountain in 2009, with three additional
      turbines of 4.5-MW capacity installed in 2012. Utilities now actively plan for
      wind generation and compete for state funding. DISCUSSION: State of Alaska energy
      policy provides the context for energy project decision-making. Substantial
      renewable energy fund (REF) awards--$202,000,000 to date for 227 REF projects in
      the first 5 cycles of funding--along with numerous energy conservation programs-
      are now in place. Increasing investment in wind is driven by multiple factors.
      Stakeholders have interests both in public policy and meeting private investment
      objectives. Wind generator investors should consider project economics and
      potential impacts of energy decisions on human health. Specifically this article
      considers: changing environmental conditions in remote Alaska villages, impacts
      associated with climate change on human health, progress in better understanding
      wind energy potential through resource assessments and new tools for detailed
      feasibility and project planning, need for comprehensive monitoring and data
      analysis, and state funding requirements and opportunity costs. CONCLUSION: The
      energy policy choices ahead for Alaska will have important implications for
      Arctic population health, especially for those villages whose relatively small
      size and remote locations make energy a key component of subsistence lifestyles
      and community sustainability. Wind generation can contribute to meeting renewable
      energy goals and is a particularly important resource for rural and remote
      Alaskan communities currently dependent on diesel fuel for generating electricity
      and heat.

PMID- 23971015
TI  - Dietary intakes of energy and macronutrients by lactating women of different
      ethnic groups living in Yakutia.
AB  - BACKGROUND: There should be a substantial increase in the intake of dietary
      energy, protein and other nutrients by lactating women, though these special
      increments can be different in different ethnic groups. OBJECTIVE: To evaluate
      the influence of maternal ethnicity and diet on the quality of breast milk and
      its potential effect on early childhood development. DESIGN: A total of 185
      mothers (150 Native and 35 Russian) living in settlements and small towns of
      rural Yakutia and 54 mothers (26 Native and 28 Russian) living in Yakutsk were
      surveyed and average food intake was recorded during 3 successive days before the
      survey was analyzed. RESULTS: The amount of protein varied from 18 to 168.3
      g/day, fat--from 12 to 176.1 g/day, energy--from 900 to 3680.4 kcal/day. Protein
      intake was at the level of current recommended dietary allowances (RDA) in
      Russians and was higher than in Natives living in rural settlements and small
      towns (p = 0.02) and in Yakutsk (p = 0.03). Carbohydrate intake was higher,
      though not significantly, in both ethnic groups compared with the current
      recommendations. Protein, fat, carbohydrates and, therefore, energy intake were
      lower (p < 0.03) in Native women living in Yakutsk compared with the intake of
      Native women living in rural settlements and small towns. CONCLUSIONS: The
      dietary intakes of energy and macronutrients depended on the place where a woman
      lived rather than on her ethnicity. Overall, energy intake was considered to be
      at the lower limit (basal energy expenditure 2002/2005) for lactating women, with
      the exception of Native women living in Yakutsk whose energy intake was below the
      lower limit.

PMID- 23971016
TI  - Burden and prevention of viral hepatitis in the Arctic region, Copenhagen,
      Denmark, 22-23 March 2012.

PMID- 23971018
TI  - Effects of increase in temperature and open water on transmigration and access to
      health care by the Nenets reindeer herders in northern Russia.
AB  - BACKGROUND: The indigenous Nenets reindeer herders in northern Russia annually
      migrate several hundred kilometers between summer and winter pastures. In the
      warming climate, ice-rich permafrost and glaciers are being significantly reduced
      and will eventually disappear from parts of the Arctic. The emergent changes in
      hydrological cycles have already led to substantial increases in open water that
      stays unfrozen for longer periods of time. This environmental change has been
      reported to compromise the nomadic Nenets' traditional way of life because the
      presence of new water in the tundra reduces the Nenets' ability to travel by
      foot, sled, or motor vehicle from the summer transitory tundra campsites in order
      to access healthcare centers in villages. New water can also impede their access
      to family and community at other herder camps and in the villages. Although
      regional and global models predicting hydrologic changes due to climate changes
      exist, the spatial resolution of these models is too coarse for studying how
      increases in open water affect health and livelihoods. To anticipate the full
      health impact of hydrologic changes, the current gap between globally forecasted
      scenarios and locally forecasted hydrologic scenarios needs to be bridged.
      OBJECTIVES: We studied the effects of the autumn temperature anomalies and
      increases in open water on health care access and transmigration of reindeer
      herders on the Kanin Peninsula. DESIGN: Correlational and time series analyses
      were completed. METHODS: The study population consisted of 370 full-time, nomadic
      reindeer herders. We utilized clinical visit records, studied surface temperature
      anomalies during autumn migrations, and used remotely sensed imagery to detect
      water bodies. Spearman correlation was used to measure the relationship between
      temperature anomalies and the annual arrival of the herders at the Nes clinic for
      preventive and primary care. Piecewise regression was used to model change in
      mean autumnal temperature anomalies over time. We also created a water body
      product to detect inter-annual changes in water area. RESULTS: Correlation
      between arrivals to the Nes clinic and temperature anomalies during the fall
      transmigration (1979-2011) was r = 0.64, p = 0.0004; 95% CI (0.31; 0.82).
      Regression analysis estimated that mean temperature anomalies during the fall
      migration in September-December were stochastically stationary pre-1991 and have
      been rising significantly (p < 0.001) since then. The rate of change was
      estimated at +0.1351 degrees C/year, SE = 0.0328, 95% CI (+0.0694, +0.2007). The
      amount of detected water fluctuated significantly interannually (620-800 km(2)).
      CONCLUSIONS: Later arrival of freezing temperatures in the autumn followed by the
      earlier spring thaws and more open water delay transmigration and reduce herders'
      access to health care. The recently observed delays in arrival to the clinic are
      likely related to the warming trend and to concomitant hydrologic changes.

PMID- 23971017
TI  - The Arctic Human Health Initiative: a legacy of the International Polar Year 2007
      2009.
AB  - BACKGROUND: The International Polar Year (IPY) 2007-2008 represented a unique
      opportunity to further stimulate cooperation and coordination on Arctic health
      research and increase the awareness and visibility of Arctic regions. The Arctic
      Human Health Initiative (AHHI) was a US-led Arctic Council IPY coordinating
      project that aimed to build and expand on existing International Union for
      Circumpolar Health (IUCH) and Arctic Council human health interests. The project
      aimed to link researchers with potential international collaborators and to serve
      as a focal point for human health research, education, outreach and communication
      activities during the IPY. The progress of projects conducted as part of this
      initiative up until the end of the Arctic Council Swedish chairmanship in May
      2013 is summarized in this report. DESIGN: The overall goals of the AHHI was to
      increase awareness and visibility of human health concerns of Arctic peoples,
      foster human health research, and promote health strategies that will improve
      health and well-being of all Arctic residents. Proposed activities to be
      recognized through the initiative included: expanding research networks that will
      enhance surveillance and monitoring of health issues of concern to Arctic
      peoples, and increase collaboration and coordination of human health research;
      fostering research that will examine the health impact of anthropogenic
      pollution, rapid modernization and economic development, climate variability,
      infectious and chronic diseases, intentional and unintentional injuries,
      promoting education, outreach and communication that will focus public and
      political attention on Arctic health issues, using a variety of publications,
      printed and electronic reports from scientific conferences, symposia and
      workshops targeting researchers, students, communities and policy makers;
      promoting the translation of research into health policy and community action
      including implementation of prevention strategies and health promotion; and
      promoting synergy and strategic direction of Arctic human health research and
      health promotion. RESULTS: As of 31 March, 2009, the official end of the IPY,
      AHHI represented a total of 38 proposals, including 21 individual Expressions of
      Intent (EoI), and 9 full proposals (FP), submitted to the IPY Joint Committee for
      review and approval from lead investigators from the US, Canada, Greenland,
      Norway, Finland, Sweden and the Russian Federation. In addition, there were 10
      National Initiatives (NI-projects undertaken during IPY beyond the IPY Joint
      Committee review process). Individual project details can be viewed at
      www.arctichealth.org. The AHHI currently monitors the progress of 28 individual
      active human health projects in the following thematic areas: health network
      expansion (5 projects), infectious disease research (7 projects), environmental
      health research (7 projects), behavioral and mental health research (4 projects),
      and outreach education and communication (5 projects). CONCLUSIONS: While some
      projects have been completed, others will continue well beyond the IPY. The IPY
      2007-2008 represented a unique opportunity to further stimulate cooperation and
      coordination on Arctic health research and increase the awareness and visibility
      of Arctic regions.

PMID- 23971019
TI  - Clinical benefits of an adherence monitoring program in the management of
      secondary hyperparathyroidism with cinacalcet: results of a prospective
      randomized controlled study.
AB  - BACKGROUND/AIMS: One of the causes of uncontrolled secondary hyperparathyroidism
      (sHPT) is patient's poor drug adherence. We evaluated the clinical benefits of an
      integrated care approach on the control of sHPT by cinacalcet. METHODS:
      Prospective, randomized, controlled, multicenter, open-label study. Fifty
      hemodialysis patients on a stable dose of cinacalcet were randomized to an
      integrated care approach (IC) or usual care approach (UC). In the IC group,
      cinacalcet adherence was monitored using an electronic system. Results were
      discussed with the patients in motivational interviews, and drug prescription
      adapted accordingly. In the UC group, drug adherence was monitored, but results
      were not available. RESULTS: At six months, 84% of patients in the IC group
      achieved recommended iPTH targets versus 55% in the UC group (P = 0.04). The mean
      cinacalcet taking adherence improved by 10.8% in the IC group and declined by
      5.3% in the UC group (P = 0.02). Concomitantly, the mean dose of cinacalcet was
      reduced by 7.2 mg/day in the IC group and increased by 6.4 mg/day in the UC group
      (P = 0.03). CONCLUSIONS: The use of a drug adherence monitoring program in the
      management of sHPT in hemodialysis patients receiving cinacalcet improves drug
      adherence and iPTH control and allows a reduction in the dose of cinacalcet.

PMID- 23971020
TI  - Immunomodulatory effect of continuous venovenous hemofiltration during sepsis:
      preliminary data.
AB  - INTRODUCTION: Severe sepsis and septic shock are the primary causes of multiple
      organ dysfunction syndrome (MODS), which is the most frequent cause of death in
      intensive care unit patients. Many pro- and anti-inflammatory mediators, such as
      interleukin-6 (IL-6), play a strategic role in septic syndrome. Continuous renal
      replacement therapy (CRRT) removes in a nonselective way pro- and anti
      inflammatory mediators. OBJECTIVE: To investigate the effects of continuous
      venovenous hemofiltration (CVVH) as an immunomodulatory treatment of sepsis in a
      prospective clinical study. METHODS: High flux hemofiltration (Qf = 60 ml/Kg/hr)
      was performed for 72 hr in thirteen critically ill patients suffering from severe
      sepsis or septic shock with acute renal failure (ARF). IL-6 gene expression was
      measured by real-time PCR analysis on RNA extracted from peripheral blood
      mononuclear cell before beginning of treatment (T0) and after 12, 24, 48, and 72
      hours (T1-4). RESULTS: Real-time PCR analysis demonstrated in twelve patients IL
      6 mRNA reduction after 12 hours of treatment and a progressive increase after 24,
      48, and 72 hours. CONCLUSIONS: We suggest that an immunomodulatory effect might
      exist during CVVH performed in critically ill patients with severe sepsis and
      septic shock. Our data show that the transcriptional activity of IL-6 increases
      during CVVH.

PMID- 23971022
TI  - Stress evaluation in adult patients with atopic dermatitis using salivary
      cortisol.
AB  - The symptoms of atopic dermatitis (AD) are often aggravated by stress, and AD can
      also lead to psychological stress due to social isolation and discrimination. The
      salivary cortisol level reflects psychological stress, and it is a good index to
      assess chronic stress. In this study, we measured the salivary cortisol levels in
      patients with AD (n = 30) and compared them with those of healthy control
      subjects (n = 42). AD patients were also evaluated for general disease severity
      using the Scoring Atopic Dermatitis (SCORAD) index. The serum levels of TARC,
      total IgE, and lactate dehydrogenase (LDH) and peripheral blood eosinophil counts
      were measured by laboratory tests. The Skindex-16 was used as a skin disease
      specific, quality of life measure, instrument. The results showed that the saliva
      cortisol level was significantly higher in AD patients compared to healthy
      subjects (P < 0.01). The salivary cortisol level was significantly correlated
      with the SCORAD index (r = 0.42, P < 0.05) while the serum TARC and LDH levels
      were positively correlated with the SCORAD index. However, no statistically
      significant correlations were observed between the salivary cortisol level and
      Skindex-16. These results suggest that the saliva cortisol level is therefore a
      useful biomarker to evaluate the stress in AD patients. 

PMID- 23971021
TI  - Children with generalised joint hypermobility and musculoskeletal complaints:
      state of the art on diagnostics, clinical characteristics, and treatment.
AB  - INTRODUCTION: To provide a state of the art on diagnostics, clinical
      characteristics, and treatment of paediatric generalised joint hypermobility
      (GJH) and joint hypermobility syndrome (JHS). METHOD: A narrative review was
      performed regarding diagnostics and clinical characteristics. Effectiveness of
      treatment was evaluated by systematic review. Searches of Medline and Central
      were performed and included nonsymptomatic and symptomatic forms of GJH (JHS,
      collagen diseases). RESULTS: In the last decade, scientific research has
      accumulated on all domains of the ICF. GJH/JHS can be considered as a clinical
      entity, which can have serious effects during all stages of life. However
      research regarding the pathological mechanism has resulted in new potential
      opportunities for treatment. When regarding the effectiveness of current
      treatments, the search identified 1318 studies, from which three were included
      (JHS: n = 2, Osteogenesis Imperfecta: n = 1). According to the best evidence
      synthesis, there was strong evidence that enhancing physical fitness is an
      effective treatment for children with JHS. However this was based on only two
      studies. CONCLUSION: Based on the sparsely available knowledge on intervention
      studies, future longitudinal studies should focus on the effect of physical
      activity, fitness, and joint stabilisation. In JHS and chronic pain, the
      effectiveness of a multidisciplinary approach should be investigated.

PMID- 23971023
TI  - Enhanced oral delivery of docetaxel using thiolated chitosan nanoparticles:
      preparation, in vitro and in vivo studies.
AB  - The aim of this study was to evaluate a nanoparticulate system with mucoadhesion
      properties composed of a core of polymethyl methacrylate surrounded by a shell of
      thiolated chitosan (Ch-GSH-pMMA) for enhancing oral bioavailability of docetaxel
      (DTX), an anticancer drug. DTX-loaded nanoparticles were prepared by emulsion
      polymerization method using cerium ammonium nitrate as an initiator.
      Physicochemical properties of the nanoparticles such as particle size, size
      distribution, morphology, drug loading, and entrapment efficiency were
      characterized. The pharmacokinetic study was carried out in vivo using wistar
      rats. The half-life of DTX-loaded NPs was about 9 times longer than oral DTX used
      as positive control. The oral bioavailability of DTX was increased to 68.9% for
      DTX-loaded nanoparticles compared to 6.5% for positive control. The nanoparticles
      showed stronger effect on the reduction of the transepithelial electrical
      resistance (TEER) of Caco-2 cell monolayer by opening the tight junctions.
      According to apparent permeability coefficient (P(app)) results, the DTX-loaded
      NPs showed more specific permeation across the Caco-2 cell monolayer in
      comparison to the DTX. In conclusion, the nanoparticles prepared in this study
      showed promising results for the development of an oral drug delivery system for
      anticancer drugs.

PMID- 23971024
TI  - Aortic dissection type A in alpine skiers.
AB  - PATIENTS AND METHODS: 140 patients with aortic dissection type A were admitted
      for cardiac surgery. Seventy-seven patients experienced their dissection in the
      winter season (from November to April). We analyzed cases of ascending aortic
      dissection associated with alpine skiing. RESULTS: In 17 patients we found skiing
      related aortic dissections. Skiers were taller (180 (172-200) cm versus 175 (157
      191) cm, P = 0.008) and heavier (90 (68-125) kg versus 80 (45-110) kg, P = 0.002)
      than nonskiers. An extension of aortic dissection into the aortic arch, the
      descending thoracic aorta, and the abdominal aorta was found in 91%, 74%, and
      69%, respectively, with no significant difference between skiers and nonskiers.
      Skiers experienced RCA ostium dissection requiring CABG in 17.6% while this was
      true for 5% of nonskiers (P = 0.086). Hospital mortality of skiers was 6% versus
      13% in nonskiers (P = 0.399). The skiers live at an altitude of 170 (0-853)
      m.a.s.l. and experience their dissection at 1602 (1185-3105; P < 0.001) m.a.s.l.
      In 82% symptom start was during recreational skiing without any trauma.
      CONCLUSION: Skiing associated aortic dissection type A is usually nontraumatic.
      The persons affected live at low altitudes and practice an outdoor sport at
      unusual high altitude at cold temperatures. Postoperative outcome is good.

PMID- 23971025
TI  - Serum ghrelin is associated with verbal learning and adiposity in a sample of
      healthy, fit older adults.
AB  - The purpose of the present investigation was to determine the relationship
      between serum ghrelin concentrations, adiposity, and verbal learning in a group
      of healthy, fit older adults. Participants were 28 healthy older adults (age:
      70.8 +/- 9.3 yrs, BMI: 27.3 +/- 5.7). Participants reported to the laboratory and
      basic anthropometric data were collected, followed by a blood draw to quantify
      serum ghrelin. Participants then underwent cognitive testing that included the
      revised Hopkins Verbal Learning Test (HVLT), as well as the Mini-Mental Status
      Exam (MMSE). The results of the MMSE test revealed that the volunteers were
      cognitively intact (MMSE 27.6 +/- 1.8). A significant correlation emerged between
      serum ghrelin concentrations, 2 trials of the HVLT (Trial 1: r = 0.316, P = 0.05;
      Trial 2: r = 0.395, P = 0.03), and the sum of three-site skinfold analysis (r =
      0.417, P = 0.015). Based upon the aforementioned relationships, it appears that
      fasting levels of serum ghrelin are related to both verbal learning and adiposity
      in healthy, fit older adults.

PMID- 23971026
TI  - Nonrigid image registration in digital subtraction angiography using multilevel B
      spline.
AB  - We address the problem of motion artifact reduction in digital subtraction
      angiography (DSA) using image registration techniques. Most of registration
      algorithms proposed for application in DSA, have been designed for peripheral and
      cerebral angiography images in which we mainly deal with global rigid motions.
      These algorithms did not yield good results when applied to coronary angiography
      images because of complex nonrigid motions that exist in this type of angiography
      images. Multiresolution and iterative algorithms are proposed to cope with this
      problem, but these algorithms are associated with high computational cost which
      makes them not acceptable for real-time clinical applications. In this paper we
      propose a nonrigid image registration algorithm for coronary angiography images
      that is significantly faster than multiresolution and iterative blocking methods
      and outperforms competing algorithms evaluated on the same data sets. This
      algorithm is based on a sparse set of matched feature point pairs and the elastic
      registration is performed by means of multilevel B-spline image warping.
      Experimental results with several clinical data sets demonstrate the
      effectiveness of our approach. 

PMID- 23971027
TI  - Myosin isoforms and contractile properties of single fibers of human Latissimus
      Dorsi muscle.
AB  - The aim of our study was to investigate fiber type distribution and contractile
      characteristics of Latissimus Dorsi muscle (LDM). Samples were collected from 18
      young healthy subjects (9 males and 9 females) through percutaneous fine needle
      muscle biopsy. The results showed a predominance of fast myosin heavy chain
      isoforms (MyHC) with 42% of MyHC 2A and 25% of MyHC 2X, while MyHC 1 represented
      only 33%. The unbalance toward fast isoforms was even greater in males (71%) than
      in females (64%). Fiber type distribution partially reflected MyHC isoform
      distribution with 28% type 1/slow fibers and 5% hybrid 1/2A fibers, while fast
      fibers were divided into 30% type 2A, 31% type A/X, 4% type X, and 2% type 1/2X.
      Type 1/slow fibers were not only less abundant but also smaller in cross
      sectional area than fast fibers. During maximal isometric contraction, type
      1/slow fibers developed force and tension significantly lower than the two major
      groups of fast fibers. In conclusion, the predominance of fast fibers and their
      greater size and strength compared to slow fibers reveal that LDM is a muscle
      specialized mainly in phasic and powerful activity. Importantly, such
      specialization is more pronounced in males than in females. 

PMID- 23971028
TI  - Secretion of biologically active heterologous oxalate decarboxylase (OxdC) in
      Lactobacillus plantarum WCFS1 using homologous signal peptides.
AB  - Current treatment options for patients with hyperoxaluria and calcium oxalate
      stone diseases are limited and do not always lead to sufficient reduction in
      urinary oxalate excretion. Oxalate degrading bacteria have been suggested for
      degrading intestinal oxalate for the prevention of calcium oxalate stone. Here,
      we reported a recombinant Lactobacillus plantarum WCFS1 (L. plantarum) secreting
      heterologous oxalate decarboxylase (OxdC) that may provide possible therapeutic
      approach by degrading intestinal oxalate. The results showed secretion and
      functional expression of OxdC protein in L. plantarum driven by signal peptides
      Lp_0373 and Lp_3050. Supernatant of the recombinant strain containing
      pLp_0373sOxdC and pLp_3050sOxdC showed OxdC activity of 0.05 U/mg and 0.02 U/mg
      protein, while the purified OxdC from the supernatant showed specific activity of
      18.3 U/mg and 17.5 U/mg protein, respectively. The concentration of OxdC protein
      in the supernatant was 8-12 MUg/mL. The recombinant strain showed up to 50%
      oxalate reduction in medium containing 10 mM oxalate. In conclusion, the
      recombinant L. plantarum harboring pLp_0373sOxdC and pLp_3050sOxdC can express
      and secrete functional OxdC and degrade oxalate up to 50% and 30%, respectively.

PMID- 23971029
TI  - A comparative study for the evaluation of two doses of ellagic acid on hepatic
      drug metabolizing and antioxidant enzymes in the rat.
AB  - The present study was designed to evaluate different doses of ellagic acid (EA)
      in vivo in rats for its potential to modulate hepatic phases I, II, and
      antioxidant enzymes. EA (10 or 30 mg/kg/day, intragastrically) was administered
      for 14 consecutive days, and activity, protein, and mRNA levels were determined.
      Although the cytochrome P450 (CYP) 2B and CYP2E enzyme activities were decreased
      significantly, the activities of all other enzymes were unchanged with the 10
      mg/kg/day EA. In addition, western-blot and qRT-PCR results clearly corroborated
      the above enzyme expressions. On the other hand, while the NAD(P)H:quinone
      oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPX), and
      glutathione S-transferase (GST) activities were increased significantly, CYP1A,
      2B, 2C, 2E, and 19 enzyme activities were reduced significantly with 30 mg/kg/day
      EA. In addition, CYP2B, 2C6, 2E1, and 19 protein and mRNA levels were
      substantially decreased by the 30 mg/kg/day dose of EA, but the CYP1A protein,
      and mRNA levels were not changed. CYP3A enzyme activity, protein and mRNA levels
      were not altered by neither 10 nor 30 mg/kg/day ellagic acid. These results
      indicate that EA exerts a dose-dependent impact on the metabolism of chemical
      carcinogens and drugs by affecting the enzymes involved in xenobiotics
      activation/detoxification and antioxidant pathways.

PMID- 23971030
TI  - Genotype-specific changes in vitamin B6 content and the PDX family in potato.
AB  - Vitamin B6 is one of the most versatile cofactors in plants and an essential
      phytonutrient in the human diet that benefits a variety of human health aspects.
      Although biosynthesis of the vitamin has been well resolved in recent years, the
      main research is currently based on Arabidopsis thaliana with very little work
      done on major crop plants. Here we provide the first report on interactions and
      expression profiles of PDX genes for vitamin B6 biosynthesis in potato and how
      vitamin B6 content varies in tubers of different genotypes. The results
      demonstrate that potato is an excellent resource for this vitamin and that strong
      natural variation in vitamin B6 content among the tested cultivars indicates high
      potential to fortify vitamin B6 nutrition in potato-based foods. 

PMID- 23971031
TI  - In vivo biocompatibility of PLGA-polyhexylthiophene nanofiber scaffolds in a rat
      model.
AB  - Electroactive polymers have applications in tissue engineering as a physical
      template for cell adhesion and carry electrical signals to improve tissue
      regeneration. Present study demonstrated the biocompatibility and
      biodegradability of poly(lactide-co-glycolide)-poly(3-hexylthiophene) (PLGA-PHT)
      blend electrospun scaffolds in a subcutaneous rat model. The biocompatibility of
      PLGA-undoped PHT, PLGA-doped PHT, and aligned PLGA-doped PHT nanofibers was
      evaluated and compared with random PLGA fibers. The animals were sacrificed at 2,
      4, and 8 weeks; the surrounding tissue along with the implant was removed to
      evaluate biocompatibility and biodegradability by histologic analysis and GPC,
      respectively. Histology results demonstrated that all scaffolds except PLGA
      undoped PHT showed decrease in inflammation over time. It was observed that the
      aligned PLGA-doped PHT fibers elicited moderate response at 2 weeks, which
      further reduced to a mild response over time with well-organized tissue structure
      and collagen deposition. The degradation of aligned nanofibers was found to be
      very slow when compared to random fibers. Further, there was no reduction in the
      molecular weight of undoped form of PHT throughout the study. These experiments
      revealed the biocompatibility and biodegradability of PLGA-PHT nanofibers that
      potentiate it to be used as a biomaterial for various applications. 

PMID- 23971032
TI  - Cloud prediction of protein structure and function with PredictProtein for
      Debian.
AB  - We report the release of PredictProtein for the Debian operating system and
      derivatives, such as Ubuntu, Bio-Linux, and Cloud BioLinux. The PredictProtein
      suite is available as a standard set of open source Debian packages. The release
      covers the most popular prediction methods from the Rost Lab, including methods
      for the prediction of secondary structure and solvent accessibility (profphd),
      nuclear localization signals (predictnls), and intrinsically disordered regions
      (norsnet). We also present two case studies that successfully utilize
      PredictProtein packages for high performance computing in the cloud: the first
      analyzes protein disorder for whole organisms, and the second analyzes the effect
      of all possible single sequence variants in protein coding regions of the human
      genome. 

PMID- 23971033
TI  - Knowledge and skill retention of in-service versus preservice nursing
      professionals following an informal training program in pediatric cardiopulmonary
      resuscitation: a repeated-measures quasiexperimental study.
AB  - Our objective was to compare the impact of a training program in pediatric
      cardiopulmonary resuscitation (CPR) on the knowledge and skills of in-service and
      preservice nurses at prespecified time points. This repeated-measures
      quasiexperimental study was conducted in the pediatric emergency and ICU of a
      tertiary care teaching hospital between January and March 2011. We assessed the
      baseline knowledge and skills of nursing staff (in-service nurses) and final year
      undergraduate nursing students (preservice nurses) using a validated
      questionnaire and a skill checklist, respectively. The participants were then
      trained on pediatric CPR using standard guidelines. The knowledge and skills were
      reassessed immediately after training and at 6 weeks after training. A total of
      74 participants-28 in-service and 46 preservice professionals-were enrolled. At
      initial assessment, in-service nurses were found to have insignificant higher
      mean knowledge scores (6.6 versus 5.8, P = 0.08) while the preservice nurses had
      significantly higher skill scores (6.5 versus 3.2, P < 0.001). Immediately after
      training, the scores improved in both groups. At 6 weeks however, we observed a
      nonuniform decline in performance in both groups-in-service nurses performing
      better in knowledge test (10.5 versus 9.1, P = 0.01) and the preservice nurses
      performing better in skill test (9.8 versus 7.4, P < 0.001). Thus, knowledge and
      skills of in-service and preservice nurses in pediatric CPR improved with
      training. In comparison to preservice nurses, the in-service nurses seemed to
      retain knowledge better with time than skills. 

PMID- 23971034
TI  - Age-related changes in hepatic activity and expression of detoxification enzymes
      in male rats.
AB  - Process of aging is accompanied by changes in the biotransformation of
      xenobiotics and impairment of normal cellular functions by free radicals.
      Therefore, this study was designed to determine age-related differences in the
      activities and/or expressions of selected drug-metabolizing and antioxidant
      enzymes in young and old rats. Specific activities of 8 drug-metabolizing enzymes
      and 4 antioxidant enzymes were assessed in hepatic subcellular fractions of 6
      week-old and 21-month-old male Wistar rats. Protein expressions of carbonyl
      reductase 1 (CBR1) and glutathione S-transferase (GST) were determined using
      immunoblotting. Remarkable age-related decrease in specific activities of CYP2B,
      CYP3A, and UDP-glucuronosyl transferase was observed, whereas no changes in
      activities of CYP1A2, flavine monooxygenase, aldo-keto reductase 1C, and
      antioxidant enzymes with advancing age were found. On the other hand, specific
      activity of CBR1 and GST was 2.4 folds and 5.6 folds higher in the senescent rats
      compared with the young ones, respectively. Interindividual variability in CBR1
      activity increased significantly with rising age. We suppose that elevated
      activities of GST and CBR1 may protect senescent rats against xenobiotic as well
      as eobiotic electrophiles and reactive carbonyls, but they may alter metabolism
      of drugs, which are CBR1 and especially GSTs substrates. 

PMID- 23971035
TI  - The effects of bariatric procedures versus medical therapy for obese patients
      with type 2 diabetes: meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To assess the effects of bariatric surgery versus medical therapy for
      type 2 diabetes mellitus. METHODS: The Cochrane library, PubMed, Embase, Chinese
      biomedical literature database, and Wanfang database up to February 2012 were
      searched. The literature searches strategies contained terms ("diabetes*",
      "surg*", and "medic*" were used), combined with the medical subject headings.
      Randomized controlled trails (RCTs) of frequently used bariatric surgery for
      obese patients with type 2 diabetes were included. Study selection, data
      extraction, quality assessment, and data analyses were performed according to the
      Cochrane standards. RESULTS: Three randomized controlled trials (RCTs) involving
      170 patients in the bariatric surgery groups and 100 patients in the medical
      therapy group were selected. Compared with medical therapy, bariatric surgery for
      type 2 diabetes can significantly decrease the levels of HbA1c, FBG, weight,
      triglycerides, and the dose of hypoglycemic, antihypertensive, and lipid-lowering
      medicine, while increasing the rate of diabetes remission (RR = 9.74, 95%CI,
      (1.36, 69.66)) and the levels of high-density lipoprotein. However, there are no
      statistical differences in serious adverse events between the surgical and
      medical groups (RR = 1.23, 95%CI, (0.80, 1.87)). CONCLUSIONS: Surgical procedures
      were more likely to help patients achieve benefits than medical therapy alone.
      Further intensive RCTs of high-quality, multiple centers and long-term followup
      should be carried out to provide more reliable evidence.

PMID- 23971036
TI  - Chronic exposure to cadmium disrupts the adrenal gland activity of the newt
      Triturus carnifex (Amphibia, Urodela).
AB  - We intended to verify the safety of the freshwater values established for cadmium
      by the European Community and the Italian Ministry of Health in drinking water (5
      MUg/L) and sewage waters (20 MUg/L). Therefore, we chronically exposed the newt
      Triturus carnifex to 5 MUg/L and 20 MUg/L doses of cadmium, respectively, during
      3 and 9 months and verified the effects on the adrenal gland. We evaluated the
      serum concentrations of adrenocorticotropic hormone (ACTH), corticosterone,
      aldosterone, norepinephrine, and epinephrine. During the 3-month exposure, both
      doses of cadmium decreased ACTH and corticosterone serum levels and increased
      aldosterone and epinephrine serum levels. During the 9-month exposure, the 5
      MUg/L dose decreased ACTH and increased aldosterone and epinephrine serum levels;
      the 20 MUg/L dose decreased norepinephrine and epinephrine serum levels, without
      affecting the other hormones. It was concluded that (1) chronic exposure to the
      safety values established for cadmium disrupted the adrenal gland activity and
      (2) the effects of cadmium were related both to the length of exposure and the
      dose administered. Moreover, our results suggest probable risks to human health,
      due to the use of water contaminated by cadmium.

PMID- 23971037
TI  - From the Mediterranean to the sea of Japan: the transcontinental odyssey of
      autoinflammatory diseases.
AB  - Autoinflammatory diseases are comprehensively caused by aberrant production of
      proinflammatory cytokines and are revealed by cyclically and spontaneously
      occurring inflammatory events. Over the last decade, there has been a revolution
      in the understanding of periodic fever syndromes, cryopyrinopathies, and skin
      disorders with pyogenic, granulomatous, or dystrophic features, which have been
      recognized across different countries spanning from the Mediterranean basin to
      the Japanese archipelago. Many children and adults with autoinflammatory diseases
      continue to elude diagnosis, and the diagnostic delay of many years puts these
      patients at risk of long-term severe complications, such as amyloidosis. Any hint
      of suspicion of autoinflammatory disease thus needs to be highlighted in various
      medical specialties, and this review examines their frequencies around the world,
      trying to match them with geographic location, ethnic and genetic data, in an
      attempt to realize a geoepidemiologic map for most of these conditions. 

PMID- 23971038
TI  - Ethanol postpolymerization treatment for improving the biocompatibility of
      acrylic reline resins.
AB  - OBJECTIVE: To evaluate the effect of postpolymerization treatment based on
      ethanol-aqueous solutions on the residual monomer (RM) content, flexural
      strength, microhardness, and cytotoxicity of hard chairside reline resins
      (Kooliner, Ufi Gel Hard). METHODS: After polymerization, specimens were immersed
      in water, 20%, 50%, or 70% ethanol solutions at 23 degrees C or 55 degrees C for
      10 minutes. Controls were left untreated. HPLC was used for the determination of
      RM content. Specimens were submitted to Vickers microhardness and 3-point loading
      flexural strength tests. Cytotoxicity of resin eluates was determined on human
      fibroblasts by assessing cellular mitochondrial function and lactate
      dehydrogenase release. RESULTS: Higher concentrations of ethanol promoted lower
      RM content at 55 degrees C in both materials. The mechanical properties were
      maintained after 50% and 20% ethanol treatments in Kooliner and Ufi Gel Hard,
      respectively. Specimens submitted to those treatments showed significant
      reduction on cytotoxicity compared to immersion in hot water, the treatment of
      choice in the recent literature. SIGNIFICANCE: Immersion of relined dentures in
      specific ethanol solutions at 55 degrees C for 10 minutes can be considered an
      effective postpolymerization treatment contributing to increase materials
      biocompatibility. The proposed protocol is expeditious and easy to achieve with
      simple equipment in a dental office.

PMID- 23971039
TI  - The anti-arthritic and immune-modulatory effects of NHAG: a novel glucosamine
      analogue in adjuvant-induced arthritis.
AB  - Rheumatoid arthritis (RA) is potentially devastating condition which lacks good
      treatment options. Pro-inflammatory cytokines interleukin-1beta (IL-1 beta ),
      tumor necrosis factor-alpha (TNF- alpha ), and oxidative stress markers such as
      nitric oxide (NO) and peroxide (PO) are mediators of RA pathogenesis. In the
      present study N-[2,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2H-pyran-3
      yl]acrylamide (NHAG), analogue of glucosamine, was evaluated in adjuvant-induced
      arthritic model of rats. The disease progression was monitored by analysing
      arthritis scoring, loss of body weight, paw oedema, and histological changes in
      joints. RA associated hyperalgesia was evaluated by gait analysis. The serum or
      plasma levels of NO, PO, glutathione (GSH) superoxide dismutase (SOD) IL-1 beta
      and TNF- alpha were analyzed to monitor the state of disease severity. The
      arthritic control animals exhibited significant increase in arthritic score (P <
      0.003) and paw oedema (P < 0.001) with parallel loss in body weight (P < 0.04).
      The NHAG-treated arthritic animals exhibited refinement in the gait changes
      associated with arthritis. NHAG also significantly decreased the NO (P < 0.02)
      and PO (P < 0.03) with concurrent increased in GSH (P < 0.04) and SOD (P <
      0.007). Both IL-1 beta (P < 0.001) and TNF- alpha (P < 0.001), were significantly
      decreased in NHAG-treated group. Thus NHAG might have a therapeutic potential for
      arthritis by exerting antioxidative and immunomodulatory effects. 

PMID- 23971040
TI  - The prognostic significance of CD44V6, CDH11, and beta-catenin expression in
      patients with osteosarcoma.
AB  - This study aimed to examine the expression of and the relationship between
      CD44V6, CDH11, and beta-catenin. The expression of these cell adhesion molecules
      was detected in 90 osteosarcoma and 20 osteochondroma specimens using
      immunohistochemistry. Associations between these parameters and
      clinicopathological data were also examined. The expression rates of CD44V6,
      CDH11, and beta-catenin were 25.0% (5/20), 70.0% (14/20), and 20.0% (4/20) in
      osteochondroma specimens, respectively. Compared to osteochondromas, the
      proportions of expression of CD44V6 and beta-catenin in osteosarcoma specimens
      increased to 65.6% (59/90) and 60.0% (54/90), respectively. However, the
      expression rate of CDH11 in osteosarcomas was reduced to 40.0% (36/90). The
      expression of these markers was significantly associated with metastasis and
      overall survival (P < 0.05). Survival analysis revealed that patients with
      increased expression of CD44V6 and beta-catenin as well as decreased expression
      of CDH11 were correlated with a shorter survival time. Multivariate analysis
      indicated that clinical stage, metastasis status, and the expression of CD44V6,
      CDH11, and beta-catenin were found to be associated with overall survival.
      Further, the expression of beta -catenin and that of CD44V6 were positively
      correlated with each other. Thus, our results indicated abnormal expression of
      CD44V6, CDH11, and beta-catenin in osteosarcomas and osteochondromas, which may
      provide important indicators for further research.

PMID- 23971041
TI  - Influence of BAK-preserved prostaglandin analog treatment on the ocular surface
      health in patients with newly diagnosed primary open-angle glaucoma.
AB  - PURPOSE: Primary open-angle glaucoma (POAG), a chronic, degenerative optic
      neuropathy, requires persistent decrease of intraocular pressure so as to prevent
      visual impairment and blindness. However, long-term use of topical ocular
      medications may affect ocular surface health. Purpose of this study was to
      evaluate the influence of BAK-preserved prostaglandin analog treatment on the
      ocular surface health in patients with newly diagnosed POAG. METHODS: 40 newly
      diagnosed POAG patients were included in this prospective study. Intraocular
      pressure (IOP), tear break-up time (TBUT), and ocular surface disease index
      (OSDI) were assessed at baseline and 3-month after starting treatment with BAK
      preserved travoprost 0.004%. RESULTS: IOP decreased in all patients from baseline
      to 3-month final visit (23.80 +/- 1.73 mmHg versus 16.78 +/- 1.27 mmHg; P <
      0.001). Mean TBUT decreased from 11.70 +/- 1.86 seconds at baseline to 8.30 +/-
      1.29 seconds at 3-month final visit (<0.001). Mean OSDI score increased from
      31.63 +/- 18.48 to 44.41 +/- 16.48 (P < 0.001). CONCLUSIONS: This study showed
      that BAK-preserved travoprost 0.004% is an effective medication in newly
      diagnosed POAG patients, but its long-term use may negatively influence ocular
      surface health by disrupting the tear film stability. Further studies are needed
      to better understand the clinical effects of different preservative types and
      concentrations on the ocular surface.

PMID- 23971042
TI  - Protective efficacy of N-(2-hydroxyphenyl) acetamide against adjuvant-induced
      arthritis in rats.
AB  - Rheumatoid arthritis is a chronic inflammatory joint disease characterized by
      synovial proliferation and tissue destruction. Proinflammatory cytokines like
      interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) play a
      key role in the disease process and elevate energy expenditure, which further
      increases the joint pain and stiffness. To explore the effects of N-(2
      hydroxyphenyl) acetamide (NA-2) on the development of arthritis, clinical signs,
      histopathology of knee joints, nociception analysis, and the serum levels of IL
      1beta and TNF-alpha were monitored. Arthritis was induced by intradermal
      administration of heat-killed adjuvant Mycobacterium tuberculosis H37Ra in rats.
      NA-2 and indomethacin treatments were started in their respective group on the
      same day when adjuvant was administered. Experiments were terminated when
      arthritic score of 4 was observed in arthritic control group. NA-2 (5 mg/kg)
      treatment significantly ameliorated the disease severity. Reduction in body
      weight and increase in paw oedema were significantly reversed in arthritic animal
      receiving NA-2. The nociceptive sensation was also inhibited in the NA-2 treated
      arthritic rats. Remission was associated with improved histology and significant
      decreased expression of serum proinflammatory cytokines (P < 0.05 for IL-1beta
      and TNF-alpha). Based on our observations, it can be suggested that NA-2
      possesses promising anti-arthritic property, and it can be used as a therapeutic
      agent for arthritis.

PMID- 23971043
TI  - Isolation and identification of free-living amoebae from tap water in Sivas,
      Turkey.
AB  - The present work focuses on a local survey of free-living amoebae (FLA) that
      cause opportunistic and nonopportunistic infections in humans. Determining the
      prevalence of FLA in water sources can shine a light on the need to prevent FLA
      related illnesses. A total of 150 samples of tap water were collected from six
      districts of Sivas province. The samples were filtered and seeded on nonnutrient
      agar containing Escherichia coli spread. Thirty-three (22%) out of 150 samples
      were found to be positive for FLA. The FLA were identified by morphology and by
      PCR using 18S rDNA gene. The morphological analysis and partial sequencing of the
      18S rDNA gene revealed the presence of three different species, Acanthamoeba
      castellanii, Acanthamoeba polyphaga, and Hartmannella vermiformis. Naegleria
      fowleri, Balamuthia mandrillaris, or Sappinia sp. was not isolated during the
      study. All A. castellanii and A. polyphaga sequence types were found to be
      genotype T4 that contains most of the pathogenic Acanthamoeba strains. The
      results indicated the occurrence and distribution of FLA species in tap water in
      these localities of Sivas, Turkey. Furthermore, the presence of temperature
      tolerant Acanthamoeba genotype T4 in tap water in the region must be taken into
      account for health risks. 

PMID- 23971045
TI  - Bees' honey protects the liver of male rats against melamine toxicity.
AB  - The protective effect of natural bees' honey to the liver of male albino rats
      against melamine toxicity was studied. Melamine supplementation at a dose of
      20000 ppm in the diet for 28 days induced adverse effects on the liver, decreased
      serum total protein and increased liver enzyme: alanine aminotransferase,
      aspartate aminotransferase, and alkaline phosphatase. Histological changes of the
      melamine supplemented group showed necrosis in the hepatic tissues around the
      central veins of the liver and precipitation of melamine crystals. Treating the
      male albino rats (that were presupplemented regularly with 20000 ppm melamine)
      with natural bees' honey at a dose of 2.5 g/kg body weight for 28 days improved
      both liver functions and increased serum protein. In addition, a positive impact
      on the shape of the cells after treatment with honey compared to the positive
      melamine supplemented group was observed. In conclusion, the results of this
      study revealed that the use of natural bees' honey has the ability to protect the
      liver of rats against the toxic effects of melamine.

PMID- 23971046
TI  - Formulation and mathematical optimization of controlled release calcium alginate
      micro pellets of frusemide.
AB  - OBJECTIVE: Frusemide loaded calcium alginate micropellets, an oral
      microparticulate delivery system, was statistically optimized exhibiting
      prolonged therapeutic action minimizing its adverse effects. METHODS: Ionotropic
      Gelation technique was adopted employing 3(2) Factorial designs and keeping the
      entire process free from organic solvents. Physicochemical and the release
      characteristics of the prepared formulations were studied, keeping variations
      only in sodium alginate (primary polymer) and Acrycoat E30D (copolymer)
      dispersion. RESULT: Sodium alginate was predominant over Acrycoat E30D in all
      batches. Nonadditives or interaction was observed to be insignificant. Multiple
      regressions produced second-order polynomial equation, and the predictive results
      obtained were validated with high degree of correlation. The in vivo study
      applauded that optimized calcium alginate micropellets of frusemide can produce a
      much greater diuretic effect over an extended period of 24 hours. CONCLUSION:
      This study reveals that the potential of a single dose of the mathematically
      optimized micro pellets of frusemide formulation is sufficient in the management
      of peripheral edema and ascites in congestive heart failure and as well in the
      treatment of chronic hypertension, leading to better patient compliance, and can
      be produced with minimum experimentation and time, proving far more cost
      effective formulation than the conventional methods of formulating dosage forms.

PMID- 23971044
TI  - Aspergillus-associated airway disease, inflammation, and the innate immune
      response.
AB  - Aspergillus moulds exist ubiquitously as spores that are inhaled in large numbers
      daily. Whilst most are removed by anatomical barriers, disease may occur in
      certain circumstances. Depending on the underlying state of the human immune
      system, clinical consequences can ensue ranging from an excessive immune response
      during allergic bronchopulmonary aspergillosis to the formation of an
      aspergilloma in the immunocompetent state. The severest infections occur in those
      who are immunocompromised where invasive pulmonary aspergillosis results in high
      mortality rates. The diagnosis of Aspergillus-associated pulmonary disease is
      based on clinical, radiological, and immunological testing. An understanding of
      the innate and inflammatory consequences of exposure to Aspergillus species is
      critical in accounting for disease manifestations and preventing sequelae. The
      major components of the innate immune system involved in recognition and removal
      of the fungus include phagocytosis, antimicrobial peptide production, and
      recognition by pattern recognition receptors. The cytokine response is also
      critical facilitating cell-to-cell communication and promoting the initiation,
      maintenance, and resolution of the host response. In the following review, we
      discuss the above areas with a focus on the innate and inflammatory response to
      airway Aspergillus exposure and how these responses may be modulated for
      therapeutic benefit. 

PMID- 23971047
TI  - Interaction between a regenerative matrix and wound bed in nonhealing ulcers:
      results with 16 cases.
AB  - A chronic wound is a wound that is delayed in one of the wound-healing stages and
      cannot progress any further. A chronic wound leaves the patient at risk of
      infection and hospitalization. In these case series, 16 patients affected by
      venous ulcers underwent Hyalomatrix PA grafting for reconstructive surgery.
      Hyalomatrix PA is a bilayered, sterile, flexible, and conformable three
      dimensional matrix made of fibers of HYAFF, a benzyl ester of hyaluronic acid,
      and a semipermeable silicone membrane. Hyalomatrix PA acts as a substitutive and
      regenerative permanent matrix able to replace the dermis providing a three
      dimensional matrix for cellular invasion and capillary growth. The silicon layer
      controls water vapor loss avoiding an excessive loss of fluids and acts as a
      semipermeable barrier to the external agents. In the presented cases, the average
      area grafted per procedure was 153 cm(2). The length of followup ranged from 0.5
      to 1 year. The final results were considered to be good in 12 cases, fair in 3
      cases, and poor in one case. This study suggests that the combination of wound
      bed preparation with application of the hyaluronic regenerative matrix can be a
      valid approach for treatment of partial thickness ulcers.

PMID- 23971048
TI  - A comparison between use of spray and freeze drying techniques for preparation of
      solid self-microemulsifying formulation of valsartan and in vitro and in vivo
      evaluation.
AB  - The objective of the present study was to develop self micro emulsifying
      formulation (SMEF) of valsartan to improve its oral bioavailability. The
      formulations were screened on the basis of solubility, stability, emulsification
      efficiency, particle size and zeta potential. The optimized liquid SMEF contains
      valsartan (20% w/w), Capmul MCM C8 (16% w/w), Tween 80 (42.66% w/w) and PEG 400
      (21.33% w/w) as drug, oil, surfactant and co-surfactant, respectively. Further,
      Liquid SMEF was adsorbed on Aerosol 200 by spray and freeze drying methods in the
      ratio of 2 : 1 and transformed into free flowing powder. Both the optimized
      liquid and solid SMEF had the particle size <200 nm with rapid reconstitution
      properties. Both drying methods are equally capable for producing stable solid
      SMEF and immediate release of drug in in vitro and in vivo conditions. However,
      the solid SMEF produced by spray drying method showed high flowability and
      compressibility. The solid state characterization employing the FTIR, DSC and XRD
      studies indicated insignificant interaction of drug with lipid and adsorbed
      excipient. The relative bioavailability of solid SMEF was approximately 1.5 to
      3.0 folds higher than marketed formulation and pure drug. Thus, the developed
      solid SMEF illustrates an alternative delivery of valsartan as compared to
      existing formulations with improved bioavailability.

PMID- 23971050
TI  - Potential of RAS inhibition to improve metabolic bone disorders.
AB  - Metabolic bone disorder is usually caused by abnormalities of minerals and
      hormones metabolism. Recently, it has been proved by several studies that the
      renin-angiotensin system (RAS) in local bone tissue is directly involved in bone
      metabolism. Activation of skeletal RAS plays an important role in bone metabolic
      disorders. Based on in vitro, in vivo, and clinical studies, this review explains
      the roles of RAS in bone metabolism and also covers the potential approaches and
      beneficial effects of RAS inhibition on bone health. Differential strategies for
      inhibiting RAS can be employed to maintain bone health, which are attributed
      primarily to the reduced level of angiotensin II (AngII) and suppressed
      stimulation of the AngII signaling pathway. The use of renin inhibitors,
      angiotensin-converting enzyme inhibitors, and AngII receptor blockers either
      individually or in combination with each other could have promising results in
      fighting bone metabolic disorders associated with other cardiovascular diseases
      as well as independent bone injuries. 

PMID- 23971049
TI  - The age-related changes in cartilage and osteoarthritis.
AB  - Osteoarthritis (OA) is closely associated with aging, but its underlying
      mechanism is unclear. Recent publications were reviewed to elucidate the
      connection between aging and OA. With increasing OA incidence, more senior people
      are facing heavy financial and social burdens. Age-related OA pathogenesis is not
      well understood. Recently, it has been realized that age-related changes in other
      tissues besides articular cartilage may also contribute to OA development. Many
      factors including senescence-related secretory phenotypes, chondrocytes' low
      reactivity to growth factors, mitochondrial dysfunction and oxidative stress, and
      abnormal accumulation of advanced glycation end products (AGEs) may all play key
      roles in the pathogenesis of age-related OA. Lately, epigenetic regulation of
      gene expression was recognized for its impact on age-related OA pathogenesis. Up
      to now, few studies have been reported about the role of miRNA and long-noncoding
      RNA (lncRNA) in age-related OA. Research focusing on this area may provide
      valuable insights into OA pathogenesis. OA-induced financial and social burdens
      have become an increasingly severe threat to older population. Age-related
      changes in noncartilage tissue should be incorporated in the understanding of OA
      development. Growing attention on oxidative stress and epigenetics will provide
      more important clues for the better understanding of the age-related OA. 

PMID- 23971051
TI  - Improvement of medium chain fatty acid content and antimicrobial activity of
      coconut oil via solid-state fermentation using a Malaysian Geotrichum candidum.
AB  - Coconut oil is a rich source of beneficial medium chain fatty acids (MCFAs)
      particularly lauric acid. In this study, the oil was modified into a value-added
      product using direct modification of substrate through fermentation (DIMOSFER)
      method. A coconut-based and coconut-oil-added solid-state cultivation using a
      Malaysian lipolytic Geotrichum candidum was used to convert the coconut oil into
      MCFAs-rich oil. Chemical characteristics of the modified coconut oils (MCOs)
      considering total medium chain glyceride esters were compared to those of the
      normal coconut oil using ELSD-RP-HPLC. Optimum amount of coconut oil hydrolysis
      was achieved at 29% moisture content and 10.14% oil content after 9 days of
      incubation, where the quantitative amounts of the modified coconut oil and MCFA
      were 0.330 mL/g of solid media (76.5% bioconversion) and 0.175 mL/g of solid
      media (53% of the MCO), respectively. MCOs demonstrated improved antibacterial
      activity mostly due to the presence of free lauric acid. The highest MCFAs-rich
      coconut oil revealed as much as 90% and 80% antibacterial activities against
      Staphylococcus aureus and Escherichia coli, respectively. The results of the
      study showed that DIMOSFER by a local lipolytic G. candidum can be used to
      produce MCFAs as natural, effective, and safe antimicrobial agent. The produced
      MCOs and MCFAs could be further applied in food and pharmaceutical industries.

PMID- 23971052
TI  - Correlations between psoriasis and inflammatory bowel diseases.
AB  - For a long time the relationship between inflammatory bowel diseases (IBDs) and
      psoriasis has been investigated by epidemiological studies. It is only starting
      from the 1990s that genetic and immunological aspects have been focused on.
      Psoriasis and IBD are strictly related inflammatory diseases. Skin and bowel
      represent, at the same time, barrier and connection between the inner and the
      outer sides of the body. The most important genetic correlations involve the
      chromosomal loci 6p22, 16q, 1p31, and 5q33 which map several genes involved in
      innate and adaptive immunity. The genetic background represents the substrate to
      the common immune processes involved in psoriasis and IBD. In the past, psoriasis
      and IBD were considered Th1-related disorders. Nowadays the role of new T cells
      populations has been highlighted. A key role is played by Th17 and T-regs cells
      as by the balance between these two cells types. New cytokines and T cells
      populations, as IL-17A, IL-22, and Th22 cells, could play an important
      pathogenetic role in psoriasis and IBD. The therapeutic overlaps further support
      the hypothesis of a common pathogenesis. 

PMID- 23971053
TI  - Ameliorative potentials of cocoyam (Colocasia esculenta L.) and unripe plantain
      (Musa paradisiaca L.) on the relative tissue weights of streptozotocin-induced
      diabetic rats.
AB  - AIM: To investigate the ameliorating potentials of cocoyam (Colocasia esculenta
      L.) and unripe plantain (Musa paradisiaca L.) incorporated feeds on the renal and
      liver growths of diabetic rats, induced with 55 and 65 mg/kg body weight of
      Streptozotocin. METHOD: The blood glucose level of the rats was measured with a
      glucometer, the protein and glucose and specific gravity (SPGR) in the urine
      samples of the rats were measured using urine assay strips and urinometer
      respectively. The chemical composition and antioxidant screening of the test
      feeds were carried out using standard techniques. RESULTS: Administration of the
      test feeds for 21 days to the diabetic rats of groups 4 and 5, resulted in 58.75%
      and 38.13% decreases in hyperglycemia and amelioration of their elevated urinary
      protein, glucose, SPGR, and relative kidney weights. The diabetic rats
      administered cocoyam incorporated feeds, had 2.71% and 19.52% increases in weight
      and growth rates, the diabetic rats administered unripe plantain incorporated
      feeds had 5.12% and 29.52% decreases in weight and growth rates while the
      diabetic control rats had 28.69%, 29.46%, 248.9% and 250.14% decreases in weights
      and growth rates. The cocoyam incorporated feeds contained higher antioxidants,
      minerals and phytochemicals except alkaloids than unripe plantain feed.
      CONCLUSION: Cocoyam and unripe plantain could be useful in the management of
      diabetic nephropathy.

PMID- 23971055
TI  - Editorial: peri-implantitis: the disease of the future.

PMID- 23971054
TI  - IL-10 induction from implants delivering pancreatic islets and hyaluronan.
AB  - Local induction of pro-tolerogenic cytokines, such as IL-10, is an appealing
      strategy to help facilitate transplantation of islets and other tissues. Here, we
      describe a pair of implantable devices that capitalize on our recent finding that
      hyaluronan (HA) promotes IL-10 production by activated T cells. The first device
      is an injectable hydrogel made of crosslinked HA and heparan sulfate loaded with
      anti-CD3/anti-CD28 antibodies and IL-2. T cells embedded within this hydrogel
      prior to polymerization go on to produce IL-10 in vivo. The second device is a
      bioengineered implant consisting of a polyvinyl alcohol sponge scaffold,
      supportive collagen hydrogel, and alginate spheres mediating sustained release of
      HA in fluid form. Pancreatic islets that expressed ovalbumin (OVA) antigen were
      implanted within this device for 14 days into immunodeficient mice that received
      OVA-specific DO.11.10 T cells and a subsequent immunization with OVA peptide.
      Splenocytes harvested from these mice produced IL-10 upon re-challenge with OVA
      or anti-CD3 antibodies. Both of these devices represent model systems that will
      be used, in future studies, to further evaluate IL-10 induction by HA, with the
      objective of improving the survival and function of transplanted islets in the
      setting of autoimmune (type 1) diabetes. 

PMID- 23971056
TI  - Which self-etch bonding systems are suitable for which clinical indications?
AB  - Self-etch bonding systems are promoted as a time-saving and user-friendly
      alternative to etch-and-rinse bonding systems. Self-etch adhesives are
      characterized by a relatively mild etching effect, resulting in a relatively low
      incidence of postoperative hypersensitivity. On the other hand, their mild
      etching effect causes a reduction in bond strength to enamel compared to that
      achieved with phosphoric acid etching. All-in-one adhesives still suffer from
      less-than-optimal initial bond strengths and from inadequate durability of the
      bond. Future developments need to focus on the elimination of water deposits
      along the adhesive interface of all-in-one adhesives. While self-etch adhesives
      may yield acceptable results when applied in combination with light-cured
      composite resin, their acidic monomers inhibit the polymerization of auto-cured
      and dual-cured composite resins. Unfortunately, most "self-cure" or "dual-cure"
      activators do not overcome this problem. This incompatibility has to be taken
      into consideration when using self-etch adhesives for adhesive cementation and
      for core build-up restorations. When assessing self-etch bonding systems, it
      should be noted that they do not represent a homogenous category of materials but
      rather comprise a great variety of different types of products, each with
      specific strengths and weaknesses. 

PMID- 23971057
TI  - Gestational diabetes.
AB  - Several studies have described an increasing prevalence of gestational diabetes
      mellitus (GDM), in line with the known increased prevalence of Type 2 diabetes.
      The risk of GDM is greater for pregnant women from selected ethnic groups (such
      as Indigenous, Asian and Indian) and for older pregnant women. 

PMID- 23971058
TI  - The metabolic syndrome.
AB  - BACKGROUND: The metabolic syndrome (MetSy) is increasingly common in Australia.
      It is associated with the rise in obesity and lifestyle risk behaviours. It is
      also controversial - its value in predicting cardiovascular disease and diabetes
      risk and in guiding therapy has been challenged. OBJECTIVE: This article aims to
      provide advice on the diagnosis of the MetSy and the principles for its
      prevention and management in the context of primary care, taking into
      consideration aetiological factors and the complexity of managing its constituent
      risk factors. DISCUSSION: Diagnosis of the MetSy is useful in focusing attention
      on central adiposity and insulin resistance as risk factors both for the
      syndrome, and cardiovascular and diabetes morbidity and mortality. Its assessment
      requires measurement of waist circumference - a simple but seldom performed
      procedure in general practice. The most essential components for the prevention
      and management of the MetSy are measures to change diet and physical activity in
      order to achieve and sustain weight loss.

PMID- 23971059
TI  - Gestational diabetes mellitus--negotiating the confusion.
AB  - BACKGROUND: Recommendations to change the diagnostic criteria for gestational
      diabetes mellitus (GDM) are controversial. Two sets of criteria are currently in
      use in Australia, which has led to considerable confusion. OBJECTIVE: This
      article discusses the rationale behind the proposed changes to the diagnostic
      criteria, and aims to clarify the current approach to the testing for and
      diagnosis of GDM in Australia. DISCUSSION: Gestational diabetes mellitus has
      adverse effects on pregnancy outcomes and implications for the long term
      wellbeing of mother and infant. New information about the relationship between
      hyperglycaemia in pregnancy and fetal outcomes has led to the formulation of
      revised recommendations for testing and diagnosis of GDM. The changes to the
      diagnostic threshold will increase the numbers of women diagnosed with GDM by up
      to 50%. Evidence that management of GDM improves neonatal outcomes mandates a
      proactive approach to diagnosis and management. General practitioners will have
      an increasing role in managing GDM.

PMID- 23971060
TI  - Obesity--recommendations for management in general practice and beyond.
AB  - BACKGROUND: It is well recognised that Australia has one of the highest
      prevalences of overweight and obesity in the developed world, and that this is
      the greatest contributing factor, along with ageing, to the chronic disease
      burden in our society. Predictions are confronting; close to 80% of Australian
      adults are predicted by be obese by the year 2025. The determinants of obesity
      are multifactorial and are influenced by early life environments as well as
      genetics. Prevention is failing due to many factors including a poor
      understanding of these determinants as well as reluctance to act at a
      government/community level. OBJECTIVE: This article aims to provide a practical
      approach to weight management in general practice with a focus on some of the
      more intensive interventions beyond the first line lifestyle modification advice.
      DISCUSSION: General practitioners are often well placed to identify overweight
      and obesity. Patient engagement in management is critical, as for any chronic
      disease. Treatment needs to be evidence based and focused on a broad range of
      health outcomes, not simply on weight. Intensive interventions to potentiate
      weight loss may involve use of very low energy diets, pharmacotherapy and
      bariatric surgery. Referral to specialist weight assessment and management
      clinics, where available may be appropriate, particularly for complex cases with
      more severe comorbidity.

PMID- 23971061
TI  - Chronic stress--an approach to management in general practice.
AB  - BACKGROUND: Stress is a word commonly used, but vaguely applied in the community.
      Stress occurs for a range of endogenous and extrinsic reasons, often unique to
      the individual, though there are some common elements. OBJECTIVE: This article
      aims to present background information on stress and provide an approach to
      managing a patient presenting with stress in the Australian general practice
      setting. DISCUSSION: Stress or cognitive arousal can have positive effects on the
      individual, but excessive or chronic stress can negatively impact health. Stress
      seems to rise from a clash between a person's perception of events and their
      expectations. The difference between stress and anxiety is determined by the
      effect of chronic stress on the individual. Helping a patient to manage their
      stress relies on understanding the individual in their own circumstances, as well
      as good communication skills.

PMID- 23971062
TI  - The bariatric surgery patient--nutrition considerations.
AB  - BACKGROUND: Bariatric surgery is an effective method of weight loss for the
      treatment of morbid obesity. It is more effective when combined with nutritional
      care, which is sometimes complex, always ongoing and differs between surgical
      procedures. In Australia, the three most common bariatric surgical procedures are
      the adjustable gastric banding, sleeve gastrectomy and the Roux-en-Y gastric
      bypass. OBJECTIVE: This article introduces the nutritional and dietary
      considerations for each procedure, and provides practical advice to support the
      general practitioner's role in managing patients who are considering, or who have
      had, bariatric surgery. DISCUSSION: While bariatric procedures influence the
      volume of food consumed, none of the procedures necessarily improve the quality
      of food consumed or compliance with recommended supplement usage, leaving
      nutrition care and food choice important lifelong considerations. Ongoing
      coordinated care by the GP, that links with the bariatric dietitian and others in
      the health management team, maximises the benefits and health outcomes for the
      patient through ongoing monitoring of nutritional status, prevention of nutrient
      deficiencies and maximising long term weight loss.

PMID- 23971063
TI  - What does an elevated troponin mean?--An update on the definition of myocardial
      infarction.
AB  - BACKGROUND: Myocardial infarction has a high rate of morbidity and mortality.
      There are major social, psychological and legal implications associated with the
      diagnosis of myocardial infarction (MI). OBJECTIVE: We present three case studies
      of different chest pain syndromes presenting with serum troponin elevation, and
      use these cases to form the basis of a review of the updated definition of MI. A
      practical approach to the diagnosis of myocardial infarction is also discussed.
      DISCUSSION: The measurement of serum troponin levels was a great diagnostic
      advance and provided powerful prognostic information. Although elevated serum
      troponin levels were originally considered pathognomonic of MI, it has become
      clear that highly sensitive troponin assays detected the presence of elevated
      troponin levels in the absence of MI. This has led to the recent 'Third universal
      definition of myocardial infarction' consensus document.

PMID- 23971064
TI  - Acute breathlessness--a case study of a chronic smoker with marijuana addiction.

PMID- 23971065
TI  - Myocardial perfusion scans.
AB  - Coronary artery disease (CAD) remains a major health concern and the leading
      cause of death in Australia. Effective assessment of patients for possible CAD is
      a common problem in general practice. Non-invasive tests such as myocardial
      perfusion scans (MPS), exercise stress tests (ESTs) and stress echocardiography
      (using exercise or dobutamine as the stressor, as appropriate) can provide useful
      diagnostic and prognostic information. This brief review discusses the role of
      MPS in the evaluation of CAD. 

PMID- 23971066
TI  - Consider HIV--testing for HIV and HIV indicator diseases.
AB  - BACKGROUND: Since the advent of highly active antiretroviral therapy (HAART),
      human immunodeficiency virus (HIV) can be considered a treatable condition. In
      Australia in 2010, 40% of people had their HIV diagnosed late, where late is
      defined as CD4 <350 cells/mm3 (CD4 normal range = 450-1,500 cells/mm3). This late
      diagnosis can significantly impact on prognosis. OBJECTIVE: This article provides
      examples of late HIV diagnosis and an update of how and when to test for HIV in
      clinical practice. DISCUSSION: While HIV is usually diagnosed in those with
      identifiable risk factors, awareness of indications to test and potential HIV
      indicator diseases can provide the general practitioner with a cue to offer
      testing to a patient. Early diagnosis of HIV offers benefits to the patient and
      the community.

PMID- 23971067
TI  - Sweet solutions for procedural pain in infants.
AB  - A sweet solution, such as sucrose or glucose, can be used for analgesia for minor
      short term procedural pain, such as immunisation, in infants up to 12 months of
      age. The sweet solution is given orally and provides short term analgesia. It has
      National Health and Medical Research Council (NHMRC) Level I evidence of efficacy
      and no serious adverse effects have been reported. This article is part of a
      series on non drug treatments summarising indications, considerations, evidence
      and where clinicians and patients can get further information.

PMID- 23971068
TI  - A young man with weight loss and lymphadenopathy--a case study.

PMID- 23971069
TI  - Managing chronic disease--patients' views and attitudes to using a broadband
      based service.
AB  - BACKGROUND: The uptake of chronic disease management initiatives among general
      practitioners remains low. cdmNet is a broadband based service used to assist
      registered care providers in developing GP management plans, team care
      arrangements, reviews and home medicines review for patients with a chronic
      disease. This study examined patients' views and attitudes of managing chronic
      disease using cdmNet. METHODS: Cross-sectional survey consisting of an anonymous
      questionnaire was completed by patients whose chronic diseases were managed using
      the broadband based service. RESULTS: Significant correlation was found between
      GPs' use of this broadband based service, and patients' perception that using a
      broadband based service will improve their control of chronic disease (p<0.001).
      Patients who felt confident their personal information would be kept private were
      also significantly more likely to recommend cdmNet (p<0.001). DISCUSSION:
      Patients who feel that technology may contribute to improving the management of
      their chronic disease and have an understanding of privacy are more likely to
      have positive views and attitudes toward using a broadband based service.

PMID- 23971070
TI  - Predictors of uptake of influenza vaccination--a survey of pregnant women in
      Western Australia.
AB  - BACKGROUND: Pregnant women are at increased risk of complications following
      influenza infection. Vaccination is the most effective preventive strategy. This
      survey aimed to determine the levels of uptake of influenza vaccine in pregnant
      women in Western Australia (WA), the proportion of women offered vaccination as
      part of antenatal care, and women's attitudes toward influenza vaccination in
      pregnancy. METHODS: Computer assisted telephone interviews were conducted with
      416 randomly selected women who were pregnant during the 2012 influenza
      vaccination season. RESULTS: Influenza vaccination coverage was 23%. Predictors
      of vaccination included believing that vaccination is safe for the infant, having
      been recommended vaccination by an antenatal care provider, and attending a
      general practitioner for most antenatal care. The majority (74%) of unvaccinated
      women reported that they would have the vaccine if their antenatal care provider
      recommended it. DISCUSSION: General practitioners lead the way in antenatal
      influenza vaccination in WA. Vaccination coverage can be improved if recommending
      and offering influenza vaccination becomes a routine part of antenatal care.

PMID- 23971071
TI  - A is for aphorism--'good judgment comes from experience; experience comes from
      bad judgment'.
AB  - 'Good judgment comes from experience; experience comes from bad judgment'. This
      aphorism was attributed to Dr Kerr L White. It makes sense. The physician who
      exercises bad judgement and makes poor decisions is likely to experience more
      disease, more complications and, through those experiences, hopefully develop
      better judgement. Unfortunately, when it comes to the practice of medicine, that
      experience can come at a high cost. So is there any truth to Dr White's comment? 

PMID- 23971072
TI  - Bioluminescence assay for the highly sensitive detection of botulinum neurotoxin
      A activity.
AB  - This article describes a novel bioluminescence assay for detecting the
      proteolytic activity of Botulinum NeuroToxins (BoNT) in complex matrices. The
      assay is capable of detecting traces of BoNT in blood samples as well as in food
      drinks. The assay was responsive to BoNT/A subtypes 1 to 5, and serotype E3 in
      buffered solutions. It was responsive to filtered Clostridium botulinum
      supernatants and BoNT/A1 in complex with neurotoxin associated proteins in
      bouillon and milk (3.8% fat) down to 400 fM after 4 h RT incubation and in
      bouillon at concentrations down to 120 fM after 21 h RT incubation. In
      combination with an immunocapture/enrichment step it could detect BoNT/A1 in
      citrated plasma at concentrations down to 30 fM (1.2 mouse LD50 per mL). The
      simplicity of the assay, combined with a demonstrated ability to lyophilize the
      reagents, demonstrates its usefulness for detection of BoNT in non-specialised
      analytical laboratories. 

PMID- 23971073
TI  - A new turn-on fluorescent chemosensor based on diketopyrrolopyrrole (DPP) for
      imaging Zn2+ in living cells.
AB  - A new turn-on fluorescent chemosensor, DPPL1, was rationally designed and
      synthesized based on diketopyrrolopyrrole (DPP), which presented high sensitivity
      and selectivity for Zn(2+). Specifically, DPPL1 presented a large emission
      enhancement and a 70 nm blue-shift upon Zn(2+) binding. (1)H NMR titrations,
      studies into the pH effects and DFT calculations further proved that this
      phenomenon was due to both photo-induced electron transfer (PET) and intra
      molecular charge transfer (ICT) processes. More importantly, DPPL1 was
      successfully used for imaging Zn(2+) in living HeLa cells. To the best of our
      knowledge, this is the first DPP-based fluorescent chemosensor to recognize
      Zn(2+) ions in living cells with a large blue-shift and a fluorescent enhancement
      based on both photo-induced electron-transfer (PET) and intramolecular charge
      transfer (ICT) effects. Meanwhile, we have also provided a new effective platform
      for the development of fluorescent chemosensors for other analytes. 

PMID- 23971074
TI  - The self-assembled Ru(bpy)3(PF6)2 nanoparticle on polystyrene microfibers and its
      application for ECL sensing.
AB  - Ruthenium nanoparticle tris(2,2'-bipyridyl)ruthenium(II) bis(hexafluorophosphate)
      (Ru(bpy)3(PF6)2, RuNP) was self-assembled on polystyrene (PS) electrospun
      microfibers. The formation of RuNP is attributed to the sulfonated PS (SPS)
      microfibers' high adsorptive capability of 94% for Ru(bpy)3(2+), as well as the
      strong interaction between the Ru(bpy)3(2+) and ionic liquid (1-butyl-3
      methylimidazolium hexafluorophosphate, BMIMPF6). The RuNP/SPS microfibers
      exhibited an enhanced electrochemiluminescence (ECL) emission, 2.3 times higher
      than that from Ru(bpy)3(2+)/SPS microfibers and 6.6 times higher than that from
      Ru(bpy)3(2+)/SPS continuous thin films. It is worthy of note that, as a result of
      the hydrophobic nature of the RuNP, the transfer of water-insoluble alpha
      naphthol is accelerated, and thus the alpha-naphthol ECL quenching efficiency is
      enhanced. An ECL sensor based on the RuNP/SPS microfibers was fabricated and used
      to detect low concentrations of alpha-naphthol. The detection limit was of 1.0 nM
      (S/N > 3), and the linear response ranged from 0 to 18 MUM. This sensor has been
      successfully applied to measure the alpha-naphthol content in pesticide carbaryl
      samples. Our work provides a very simple and cost-effective method to fabricate
      RuNP on polymer microfibers with great potential in the field of
      chemo/biosensors.

PMID- 23971075
TI  - Raman micro spectroscopy study of the interaction of vincristine with A549 cells
      supported by expression analysis of bcl-2 protein.
AB  - Understanding the interaction of anticancer drugs with model cell lines is
      important to elucidate the mode of action of these drugs as well as to develop
      cost effective and rapid screening methods. Raman spectroscopy has been
      demonstrated to be a valuable technique for high throughput, noninvasive
      analysis. The interaction of vincristine with a human lung adenocarcinoma cell
      line (A549) was investigated using Raman micro spectroscopy. The results were
      correlated with parallel measurements from the MTT cytotoxicity assay, which
      yielded an IC50 value of 0.10 +/- 0.03 MUM. The Raman spectral data acquired from
      vincristine treated A549 cells was analysed to understand its interaction with
      the nucleus in the cell and elucidate DNA intercalation. The dose dependent
      spectral changes in the nucleus are analysed by PLS-Jack knifing for the
      identification of the more significant changes associated with the mode of action
      of the drug. Results are correlated with a similar dose dependent expression
      analysis of the bcl-2 protein, an anti-apoptotic protein associated with DNA
      damage, in the vincristine treated A549 cells using flow cytometry. The results
      indicate the co-existence of two modes of action, microtubule binding at low
      doses and DNA intercalation at high doses. 

PMID- 23971076
TI  - Stripping voltammetric detection of insulin at liquid-liquid microinterfaces in
      the presence of bovine albumin.
AB  - Electrochemistry at the interface between two immiscible electrolyte solutions
      (ITIES) provides a platform for label-free detection of biomolecules. In this
      study, adsorptive stripping voltammetry (AdSV) was implemented at an array of
      microscale ITIES for the detection of the antidiabetic hormone insulin. By
      exploiting the potential-controlled adsorption of insulin at the ITIES, insulin
      was detected at 10 nM via subsequent voltammetric desorption. This is the lowest
      detected concentration reported to-date for a protein by electrochemistry at the
      ITIES. Surface coverage calculations indicate that between 0.1 and 1 monolayer of
      insulin forms at the interface over the 10-1000 nM concentration range of the
      hormone. In a step toward assessment of selectivity, the optimum adsorption
      potentials for insulin and albumin were determined to be 0.900 V and 0.975 V,
      respectively. When present in an aqueous mixture with albumin, insulin was
      detected by tuning the adsorption potential to 0.9 V, albeit with reduced
      sensitivity. This provides the first example of selective detection of one
      protein in the presence of another by exploiting optimal adsorption potentials.
      The results presented here provide a route to the improvement of detection limits
      and achievement of selectivity for protein detection by electrochemistry at the
      ITIES. 

PMID- 23971077
TI  - Forensic electrochemistry: the electroanalytical sensing of Rohypnol(r)
      (flunitrazepam) using screen-printed graphite electrodes without recourse for
      electrode or sample pre-treatment.
AB  - The electroanalytical sensing of Rohypnol(r) (flunitrazepam) is reported for the
      first time utilising screen-printed graphite electrodes without the requirement
      for any additional pre-treatment or modification. The methodology is shown to be
      useful for quantifying low levels (MUg mL(-1)) of Rohypnol(r) in not only
      buffered solutions but also two internationally favoured drinks: Coca ColaTM and
      the alcopop WKDTM without any sample pre-treatment. The current analytical
      approaches for the sensing of Rohypnol(r) are also summarised within this paper.
      The niche of this electroanalytical protocol is the lack of the requirement of
      any pre-treatment of the sample/beverage or electrode modification (cleaning, pre
      treatment etc.) for the determination of Rohypnol(r) in beverages and offers a
      potential rapid, cost-effective, yet suitably sensitive and accurate screening
      solution to the problem posed by coloured drinks to products such as the colour
      changing 'Smart Cup'. 

PMID- 23971078
TI  - Photonic crystal enhanced microscopy for imaging of live cell adhesion.
AB  - A form of microscopy that utilizes a photonic crystal biosensor surface as a
      substrate for cell attachment enables label-free, quantitative, submicron
      resolution, time-resolved imaging of cell-surface interactions without cytotoxic
      staining agents or temporally-unstable fluorophores. Other forms of microscopy do
      not provide this direct measurement of live cell-surface attachment localization
      and strength that includes unique, dynamic morphological signatures critical to
      the investigation of important biological phenomena such as stem cell
      differentiation, chemotaxis, apoptosis, and metastasis. Here, we introduce
      Photonic Crystal Enhanced Microscopy (PCEM), and apply it to the study of murine
      dental stem cells to image the evolution of cell attachment and morphology during
      chemotaxis and drug-induced apoptosis. PCEM provides rich, dynamic information
      about the evolution of cell-surface attachment profiles over biologically
      relevant time-scales. Critically, this method retains the ability to monitor cell
      behavior with spatial resolution sufficient for observing both attachment
      footprints of filopodial extensions and intracellular attachment strength
      gradients. 

PMID- 23971079
TI  - Luminescent carbon dots in a new magnesium aluminophosphate zeolite.
AB  - A new magnesium aluminophosphate JU92-300 with novel zeotype structure and 8-ring
      channels has been prepared by calcination of microporous JU-92 under 300  degrees
      C. Well dispersed C-dots are prepared by using JU92-300 as a support host. Such C
      dots@zeolite materials exhibit excitation-dependent photoluminescent behavior, as
      well as tunable fluorescence with high quantum yields. 

PMID- 23971080
TI  - In Person.

PMID- 23971081
TI  - Robyn J. Barst, MD.

PMID- 23971082
TI  - Sleep deprivation: a call for institutional rules.

PMID- 23971083
TI  - Abstracts of the G-I-N (Guidelines International Network) Conference 2013. San
      Francisco, California, USA. August 18-21, 2013.

PMID- 23971084
TI  - Exercise is medicine: some cautionary remarks in principle as well as in
      practice.
AB  - On the basis of extensive research on the relationship between physical activity,
      exercise and health, as well as strong support from policymakers and
      practitioners, the "Exercise is Medicine" initiative has become something of a
      linchpin in the agenda for modern healthcare reform and reflects a broader
      acceptance that the philosophy of health politics must shift from social
      engineering to performativity. However, in spite of the avowed commitment to
      encouraging individuals to take on a more reflexive relation to their health, it
      remains unclear as to whether an initiative such as this is, unambiguously, a
      good thing. In this paper, a number of cautionary remarks are made with respect
      to "Exercise is Medicine" in principle as well as in practice. Firstly, it is
      argued that equating exercise with medicine is to equate it with a definition of
      and relation to the body to which it is not entirely akin. And secondly, it is
      argued that any proposed alignment of the fitness and healthcare industries needs
      further critical examination, a realigning of interests, and a thorough
      reconsideration of their suitability of fit.

PMID- 23971085
TI  - Abstracts of ICIEM 2013, the 12th International Congress of Inborn Errors of
      Metabolism. Barcelona, Spain. September 3-6, 2013.

PMID- 23971086
TI  - Abstracts of the 49th Congress of the European Societies of Toxicology (EUROTOX).
      September 1-4, 2013. Interlaken, Switzerland.

PMID- 23971087
TI  - Abstracts of the Shock Society Fifth Congress of the European Shock Society.
      Vienna, Austria. September 12-14, 2013.

PMID- 23971088
TI  - In Reply.

PMID- 23971089
TI  - Dennis Lo elected to the US National Academy of Sciences.

PMID- 23971090
TI  - Light chain deposition.

PMID- 23971091
TI  - Response.

PMID- 23971092
TI  - Retraction.

PMID- 23971093
TI  - An interview with Dr. Edward L. Deci, codeveloper of self-determination theory.
      Interview by Paul Terry.

PMID- 23971094
TI  - Thoughts on the genesis of self-determination theory.

PMID- 23971095
TI  - Reflections on the roots of self-determination.

PMID- 23971096
TI  - How can health promotion professionals support autonomous motivation?

PMID- 23971097
TI  - Talking clean. For good oral care, get back to the basics.

PMID- 23971098
TI  - Lessons learned: Teaching schools about the rights of children with diabetes.

PMID- 23971099
TI  - Get schooled on 504 plans: How to protect your child's right to a fair and equal
      education.

PMID- 23971100
TI  - Clinical cost reduction in a value-based world.
AB  - it's not news to anyone in healthcare that hospitals and health systems need to
      look differently at how they manage the costs of delivering care. A reimbursement
      system based on prudence, prevention and value will gradually replace the flawed
      structure that has for many s fostered consumption, volume and excess.

PMID- 23971101
TI  - Screening--benefits or harms?

PMID- 23971102
TI  - An adapted triage tool (ETAT) at Red Cross War Memorial Children's Hospital
      Medical Emergency Unit, Cape Town, South Africa: an evaluation.

PMID- 23971103
TI  - Triage--keep it simple, swift, safe and scientific.

PMID- 23971104
TI  - Artesunate v. quinine for severe malaria.

PMID- 23971105
TI  - Asthma guidelines: why aminophylline?

PMID- 23971106
TI  - Late termination of pregnancy: maternal counselling and fetal rights.

PMID- 23971107
TI  - Author reply: To PMID 23237125.

PMID- 23971108
TI  - Autism--mitigating a global epidemic.

PMID- 23971109
TI  - Whistle blast on private healthcare's 'zero sum game'.

PMID- 23971110
TI  - 'Jack-knife' scrum victim: 8 years on, no payout.

PMID- 23971111
TI  - Karabus' 'Argo moment' a long time coming.

PMID- 23971112
TI  - Is the mass circumcision drive in KwaZulu-Natal involving neonates and children
      less than 16 years of age legal? What should doctors do?
AB  - As a result of the revival of male circumcision among Zulu males as a cultural
      practice and an attempt to reduce the incidence of HIV infection, the KwaZulu
      Natal government has implemented a programme of mass circumcision of Zulu males.
      The question arises whether the implementation of such a programme on neonates
      and children under 16 years of age is legal in terms of the Constitution and the
      Children's Act. The answer hinges on whether the circumcision is done as a
      cultural practice or for medical reasons. Doctors are provided with guidance as
      to what they should do when faced with neonates or males under 16 years of age
      being presented for circumcision.

PMID- 23971113
TI  - Private theatre utilisation in South Africa: a case study.
AB  - INTRODUCTION: A large private operating theatre complex was investigated to
      address the lack of published South African benchmarks for utilisation. All major
      theatres were staffed during normal working hours (07h00 - 19h00), emergency
      cases being provided for on an ad hoc basis through spare capacity. METHODS: An
      extensive billing database, amounting to 28 991 records of procedures performed
      during normal working hours and spanning the period October 2007 - February 2010,
      was data-mined using Visual Basic for Applications (VBA) scripts. Theatre
      utilisation was analysed per day, per theatre. RESULTS: The results showed an
      average utilisation of 43% with significant variation in day-to-day operations.
      If the very underutilised minor theatre was excluded from the analysis, overall
      utilisation rose to 48%. Individual theatre utilisation ranged from 14% to 61%.
      An analysis of change in utilisation with time during a day showed that peak
      utilisation of 71% was achieved at 09h30 (90 minutes after lists start).
      Utilisation dropped to 25% at the end of the working day and was sustained for
      some time after hours. CONCLUSION: The 48% utilisation observed was significantly
      lower than the global benchmark of between 70% and 80%.

PMID- 23971114
TI  - Toxicovigilance: experience of the Tygerberg Poison Information Centre in
      context.

PMID- 23971115
TI  - Screening for chronic diseases in South Africa.

PMID- 23971116
TI  - Paradigm shift needed for cervical cancer: HPV infection is the real epidemic.

PMID- 23971117
TI  - Toxicovigilance. I: A survey of acute poisonings in South Africa based on
      Tygerberg Poison Information Centre data.
AB  - BACKGROUND: The incidence and spectrum of acute poisonings in South Africa are
      unknown. Poisoning data can be derived from sources such as hospital admission
      records and poison information centre (PIC) records. OBJECTIVES: This study was
      conducted to examine the extent of the problem and to identify trends and
      toxicovigilance issues using PIC data. METHODS: A survey was conducted based on
      Tygerberg Poison Information Centre (TPIC) consultations over 1 year. TPIC
      consultation forms were analysed for patient demographics and causes of
      poisoning. RESULTS: The TPIC dealt with 4 771 consultations related to human
      exposures to poisonous substances. The study showed that accidental exposure was
      more common than intentional poisoning (65.2% v. 34.8%); that 55.8% of cases were
      adults, of which 57.6% were females; and that 61.4% of adult cases were
      intentional exposures, and of these 64.3% were females. There was a predominance
      of accidental exposures (98.8%) and a male predominance (59.7%) in children.
      Categories of poisoning exposures across all age groups were non-drug chemicals
      (52.7%), medicines (35.2%) and biological toxins (12.6%). Pesticides (34.8%),
      irritant/corrosive substances (27.7%) and volatile hydrocarbons (8.3%) were the
      most common classes of non-drug chemical exposures. Cholinesterase inhibitors
      (8.8%), anticoagulant rodenticides (7.1%) and pyrethroids (5.0%) were the most
      commonly ingested non-drug chemicals. Aldicarb and amitraz poisoning were
      identified as toxicovigilance targets. Analgesics (26.1%) were the most common
      class of medicine-related exposure, and paracetamol (15.8%), benzodiazepines
      (9.2%) and antihistamines (5.2%) were the most common medicine-related exposures.
      CONCLUSION: The study provided information on evolving trends and identified
      toxicovigilance targets and the need for continuing toxicology education
      programmes.

PMID- 23971118
TI  - Toxicovigilance. II: A survey of the spectrum of acute poisoning and current
      practices in the initial management of poisoning cases admitted to South African
      hospitals.
AB  - BACKGROUND: Initial management of acute poisoning in South African (SA) hospitals
      such as gastric decontamination and use of antidotes has not been evaluated
      relevant to current international guidelines. OBJECTIVES: The objective of this
      study was to conduct a toxicovigilance survey of SA hospital admissions to assess
      the spectrum of acute poisonings, current practices in gastric decontamination,
      and use of antidotes in the management of acute poisoning. METHODS: A survey was
      undertaken based on acute poisoning admissions to Tygerberg Academic Hospital
      (TAH) as well as hospital-based poisoning consultations with the Tygerberg Poison
      Information Centre (TPIC) over 1 year to investigate trends in admissions and the
      initial management of hospital admissions for acute poisoning. TAH admission
      details and TPIC consultation forms for hospital-based cases were analysed for
      patient demographics, causes of poisoning, gastric decontamination measures and
      use of antidotes. RESULTS: There were 662 admissions to TAH and 2 459 hospital
      based TPIC consultations. Paracetamol and cholinesterase inhibitors were the most
      common exposures in both studies. Gastric decontamination measures were employed
      at TAH in 47.7% of cases and in 5.3% of hospital cases reported to the TPIC. Of
      these, 67.4% in the TAH study and 26.1% in the TPIC study did not comply with
      international guidelines. N-acetylcysteine was administered inappropriately in
      22.1% of the paracetamol poisoning cases at TAH and in 1.6% in the TPIC study.
      Atropine was administered unnecessarily in 12 of 30 TPIC cases. CONCLUSION: This
      study has identified the need for directed training on gastric decontamination
      measures and use of antidotes and, combined with the previous study, has
      identified national trends in poisoning.

PMID- 23971119
TI  - Vital signs for children at triage: a multicentre validation of the revised South
      African Triage Scale (SATS) for children.
AB  - OBJECTIVE: To validate a revised version of the paediatric South African Triage
      Scale (SATS) against admission as a reference standard and compare the
      sensitivity of triage using: (i) clinical discriminators; (ii) an age-appropriate
      physiological composite score; and (iii) a combination of both. METHODS: A
      prospective cohort study was undertaken validating the revised paediatric SATS
      against outcome markers of children at six emergency centres during a 2-month
      period in 2011. The primary outcome marker was the proportion of children
      admitted. Validity indicators including sensitivity (Se), specificity, positive
      predictive value and negative predictive value (NPV) were used to estimate the
      validity. Associated percentages for over-/under-triage were used to further
      assess practical application of the paediatric SATS. RESULTS: A total of 2 014
      children were included. The percentage of hospital admissions increased with an
      increase in the level of urgency from 5% in the non-urgent patients to 73% in the
      emergency patients. The data demonstrated that sensitivity increased
      substantially when using the SATS, which is a combination of clinical
      discriminators and the Triage Early Warning Score (TEWS) (Se 91.0%, NPV 95.3%),
      compared with use of clinical discriminators in isolation (Se 57.1%, NPV 86.3%)
      or the TEWS in isolation (Se 75.6%, NPV 89.1%). CONCLUSION: The results of this
      study illustrate that the revised paediatric SATS is a safe and robust triage
      tool.

PMID- 23971120
TI  - Provincial screening rates for chronic diseases of lifestyle, cancers and HIV in
      a health-insured population.
AB  - BACKGROUND: Screening for asymptomatic diseases can reduce the burden of
      morbidity and mortality in all population groups. There is widespread
      geographical variation in the quality of care. Few data are available on national
      screening rates in South Africa and how these vary across the provinces.
      OBJECTIVE: To examine screening rates for chronic diseases of lifestyle (CDL),
      HIV and cancer in a privately insured population for a single insurer across all
      nine provinces in South Africa, and to determine whether or not there are any
      differences between the provinces. METHOD: Screening rates were calculated as the
      proportion of eligible members who had received screening tests during 2011 in
      each province. Mean screening rates were compared between Gauteng and the other
      eight provinces. RESULTS: Nationwide screening rates were 20.5% for CDL, 8.2% for
      HIV and 31.9% for cancer. Despite similar insurance coverage, screening rates
      ranged from 0.3% to 0.95% lower in other provinces compared with Gauteng. Of all
      the provinces, Gauteng had the highestannual screening rates for CDL, breast
      cancer, prostate cancer and HIV (p < 0.001), while the Western Cape had the
      highest rate for cervical cancer (p < 0.001). CONCLUSION: There is much variation
      in preventive care utilisation across the provinces within this health-insured
      population. Provinces with more abundant healthcare resources have higher
      screening rates. Further research is required to understand the reasons for the
      variation, given equal payment access.

PMID- 23971121
TI  - Age-specific prevalence of cervical human papillomavirus infection and
      cytological abnormalities in women in Gauteng Province, South Africa.
AB  - BACKGROUND: Women accessing the public health system in Gauteng province, South
      Africa are largely unscreened for cervical cancer and have a high background
      prevalence of human immunodeficiency virus (HIV) infection. OBJECTIVES: This
      cross-sectional study describes the age-specific prevalence of human
      papillomavirus (HPV) infection and cytological abnormalities among this urban and
      peri-urban population. METHOD: Over the period March 2009 - September 2011, 1 524
      women attending public sector primary healthcare clinics were invited to
      participate in a cervical cancer screening study. All participants were screened
      with conventional cytology and HPV testing undertaken using the HPV linear array
      genotyping kit (Roche Molecular Systems). RESULTS: Of 1 472 women with valid
      cytology results, abnormalities were detected in 17.3% (n = 255), of which 9.1%
      (n = 134) were high-grade squamous intraepithelial lesions, and 0.5% (n = 8)
      suggestive of squamous carcinoma. Of the 1,445 women with complete data, the
      overall and high-risk HPV DNA prevalences were 74.6% (n = 1 078) and 54.3% (n =
      784), respectively. HPV type 16 and/or 18 were detected in 19.5% (n = 282) of
      women. Age-specific prevalence of HPV showed a plateau-shaped curve. CONCLUSIONS:
      The prevalences of HPV infection and abnormal cytology were much higher than
      previously reported in general populations in South Africa and elsewhere. Higher
      age-specific prevalence and similar plateau-like age-specific epidemiological
      curves have previously only been described in studies among HIV-positive women.
      These findings have implications for planning and development of cervical
      screening programmes in developing countries with largely unscreened populations
      with a high background prevalence of HIV.

PMID- 23971122
TI  - High uptake of Gardasil vaccine among 9 - 12-year-old schoolgirls participating
      in an HPV vaccination demonstration project in KwaZulu-Natal, South Africa.
AB  - BACKGROUND: Cervical cancer is linked to infection of the cervix by oncogenic
      human papillomavirus (HPV) subtypes. The quadrivalent Gardasil vaccine (against
      HPV types 6, 11, 16, 18), recommended in girls 9 - 12 years of age, has been
      shown to be safe, immunogenic and efficacious, with minimal or no side-effects.
      AIM: To demonstrate the capacity of school health teams to carry out vaccinations
      within a school environment. OBJECTIVES: To assess the uptake of 3 doses of the
      vaccine, document lessons learnt and provide recommendations for a national
      rollout of school-based HPV vaccination for learners. METHODS: Female learners
      (age 9 - 12 years) from 31 primary schools in Nongoma and Ceza districts (KwaZulu
      Natal province, South Africa) were identified for inclusion in the vaccination
      programme. The 3 doses of vaccine were administered by existing school health
      teams. Education and training sessions were held with all stakeholders:
      provincial departments of health and education; school health teams; primary
      healthcare nurses; hospital doctors and nurses; private practitioners; school
      principals, teachers and governing bodies; parents; and community and traditional
      leaders. RESULTS: The overall uptake of the vaccine was found to be high: 99.7%,
      97.9% and 97.8% for the first, second and third doses respectively (N = 963). No
      adverse events were attributed to the HPV vaccine. CONCLUSION: This project
      demonstrated the successful implementation of HPV vaccination among learners
      (ages 9 - 12 years) using school health teams.

PMID- 23971123
TI  - Risk of nevirapine-associated Stevens-Johnson syndrome among HIV-infected
      pregnant women: the Medunsa National Pharmacovigilance Centre, 2007 - 2012.
AB  - BACKGROUND: Stevens-Johnson syndrome (SJS) is an acute life-threatening condition
      often elicited by drugs. The government's indecisiveness in deciding to stop the
      use of nevirapine (NVP) in HIV-infected pregnant women owing to the increase of
      SJS among this population group in South Africa prompted this investigation.
      OBJECTIVES: To investigate if pregnancy is a risk factor for SJS among HIV
      infected women taking NVP-containing regimens and registered within the Medunsa
      National Pharmacovigilance Centre database. METHODS: A matched case-control study
      with 5:1 matching was conducted. Women with SJS (cases) taking NVP-containing
      regimens were matched with women without SJS (controls) taking NVP-containing
      regimens. Controls were randomly selected and matched to cases by hospital, age,
      treatment duration and CD4 count. Conditional logistic regression was used to
      determine if pregnancy was a risk factor for SJS. RESULTS: Six SJS cases were
      identified and 30 controls selected. The median age of both cases and controls
      was 29 years and the average CD4 counts were 237 and 234 cells/microl
      respectively. Subjects were on NVP treatment for 18 - 31 days before the onset of
      SJS. Controls did not develop SJS after treatment of between 1 and 365 days.
      Pregnancy increased the chances of developing SJS 14-fold (OR 14.28, p = 0.006,
      95% CI 1.54 - 131.82). CONCLUSIONS: NVP-containing ARV regimens taken during
      pregnancy increase the risk of developing SJS. Healthcare workers are advised to
      offer informed consent to patients and recommend effective contraception methods
      if NVP treatment is considered. In the light of our findings, further studies of
      the association between NVP, pregnancy and SJS are necessary before general
      conclusions can be reached.

PMID- 23971124
TI  - Bone marrow morphological features and diagnostic value in paediatric
      disseminated tuberculosis in the setting of increased HIV prevalence.
AB  - BACKGROUND: Disseminated tuberculosis (TB) is a life-threatening condition which
      is often a challenge to diagnose. When to use bone marrow biopsies to diagnose
      disseminated TB in paediatrics is always a dilemma, from both a clinical and
      laboratory perspective, as there are no clear guidelines. Our study primarily
      aims to evaluate the role of routine bone marrow biopsies, and to compare
      peripheral blood cultures to aspirate cultures in the diagnosis of disseminated
      TB, in a paediatric population at Tygerberg Hospital. In addition, we set out to
      assess the morphology of bone marrow biopsies in this study. METHODS: A
      prospective study, consisting of 35 paediatric patients, was conducted from
      October 2007 to November 2008. Bone marrow aspirate and trephine biopsies were
      performed on all patients and examined. Granulomas with Ziehl-Neelsen (ZN)
      positivity were sought on the trephine biopsy for the presence of acid-fast
      bacilli (AFB). RESULTS: Of the 35 children in this study, 25 were eventually
      diagnosed with TB on the basis of a multitude of clinical and laboratory
      parameters. The remaining 10 had alternative diagnoses. Peripheral blood TB
      cultures were positive in less than 1%. Bone marrow aspirate cultures were
      positive in less than 5%. Bone marrow trephine biopsies showed granulomas with ZN
      positivity in 11% of the 35 patients. CONCLUSION: Our results, generally, agree
      with the current evidence. Bone marrow biopsies in children should be performed
      if there is a strong clinical suspicion of disseminated TB, when no alternative
      non-invasive confirmatory test is available.

PMID- 23971125
TI  - Hepatitis B virus in HIV-infected patients in northeastern South Africa:
      prevalence, exposure, protection and response to HAART.
AB  - OBJECTIVE: Hepatitis B virus (HBV) and HIV are endemic infections in many African
      countries. The objectives of this study were to determine the levels of exposure
      to, and protection from, HBV, as well as the prevalence of HIV/HBV co-infection
      and the response of HBV to highly active anti-retroviral therapy (HAART) in a
      cross-section of HIV-infected patients in north-eastern South Africa. STUDY
      DESIGN: This was a laboratory-based, unmatched study. Three hundred and eighty
      patients were screened by ELISA for HBsAg, anti-HBc and anti-HBs. Samples non
      reactive for HBsAg but reactive for anti-HBc were examined for occult HBV
      infection. Response to HAART was assessed by measuring HBV viral loads,
      seroconversion from HBeAg to anti-HBe, and levels of aminotransferase. RESULTS:
      Of the study population of 380, 60% (95% CI 54.8 - 64.9) were exposed to HBV
      based on HBsAg, anti-HBs or anti-HBc; 20% (95% CI 16.1 - 24.4) had active HBV
      infection, based on HBsAg serology, and 30% (95% CI 25.2 - 35.2) were protected,
      based on anti-HBs levels > or = 10 IU/l. Of 181 HBsAg-negative individuals, 61
      had HBV occult infection (33.7%, 95% CI 26.9 - 41.1). The differences in
      prevalence were not statistically significant when gender, marital status and
      CD4+ cell counts were considered. Of 21 patients analysed, 80% showed adequate
      response to the first-line HAART regimen (stavudine/lamivudine/efavirenz or
      nevirapine) after 12 months of use. CONCLUSION: The study confirms the higher
      level (60%) of exposure to HBV in HIV patients in Limpopo Province, as well as
      the high (20%) prevalence of HBsAg positivity and occult hepatitis B (33.7%).
      However, further studies are warranted to corroborate the benefit of lamivudine
      containing HAART regimens, as HIV/HBV co-infected patients have a higher liver
      related mortality if hepatitis B is not treated.

PMID- 23971128
TI  - [Nosocomial infections--infections associated with providing health care].

PMID- 23971129
TI  - [Head and neck cancer].

PMID- 23971131
TI  - [II. Superselective arterial infusion for chemotherapy].

PMID- 23971130
TI  - [I. Supportive care against chemotherapy for head and neck neoplasm-aiming better
      quality of life].

PMID- 23971132
TI  - [III. Head and neck cancer and human papillomavirus].

PMID- 23971133
TI  - [IV. Molecular targeting therapy for head and neck cancer].

PMID- 23971134
TI  - The Biology of Plants. Foreword.

PMID- 23971135
TI  - The case of the elusive Mr. Lucas, the mysterious Major Heitland, et. al.

PMID- 23971136
TI  - A small step in the right direction.

PMID- 23971137
TI  - Oral pregabalin holds promise to reduce  pain after cardiac surgery.

PMID- 23971138
TI  - [Development of diagnostic and therapeutic modalities for cancer by targeting
      protein phosphatases].

PMID- 23971139
TI  - Cost approach of health care entity intangible asset valuation.
AB  - In the valuation synthesis and conclusion process, the analyst should consider
      the following question: Does the selected valuation approach(es) and method(s)
      accomplish the analyst's assignment? Also, does the selected valuation approach
      and method actually quantify the desired objective of the intangible asset
      analysis? The analyst should also consider if the selected valuation approach and
      method analyzes the appropriate bundle of legal rights. The analyst should
      consider if there were sufficient empirical data available to perform the
      selected valuation approach and method. The valuation synthesis should consider
      if there were sufficient data available to make the analyst comfortable with the
      value conclusion. The valuation analyst should consider if the selected approach
      and method will be understandable to the intended audience. In the valuation
      synthesis and conclusion, the analyst should also consider which approaches and
      methods deserve the greatest consideration with respect to the intangible asset's
      RUL. The intangible asset RUL is a consideration of each valuation approach. In
      the income approach, the RUL may affect the projection period for the intangible
      asset income subject to either yield capitalization or direct capitalization. In
      the cost approach, the RUL may affect the total amount of obsolescence, if any,
      from the estimate cost measure (that is, the intangible reproduction cost new or
      replacement cost new). In the market approach, the RUL may effect the selection,
      rejection, and/or adjustment of the comparable or guideline intangible asset sale
      and license transactional data. The experienced valuation analyst will use
      professional judgment to weight the various value indications to conclude a final
      intangible asset value, based on: The analyst's confidence in the quantity and
      quality of available data; The analyst's level of due diligence performed on that
      data; The relevance of the valuation method to the intangible asset life cycle
      stage and degree of marketability; and The degree of variation in the range of
      value indications. Valuation analysts value health care intangible assets for a
      number of reasons. In addition to regulatory compliance reasons, these reasons
      include various transaction, taxation, financing, litigation, accounting,
      bankruptcy, and planning purposes. The valuation analyst should consider all
      generally accepted intangible asset valuation approaches, methods, and
      procedures. Many valuation analysts are more familiar with market approach and
      income approach valuation methods. However, there are numerous instances when
      cost approach valuation methods are also applicable to the health care intangible
      asset valuation. This discussion summarized the analyst's procedures and
      considerations with regard to the cost approach. The cost approach is often
      applicable to the valuation of intangible assets in the health care industry.
      However, the cost approach is only applicable if the valuation analyst (1)
      appropriately considers all of the cost components and (2) appropriately
      identifies and quantifies all obsolescence allowances. Regardless of the health
      care intangible asset or the reason for the valuation, the analyst should be
      familiar with all generally accepted valuation approaches and methods. And, the
      valuation analyst should have a clear, convincing, and cogent rationale for (1)
      accepting each approach and method applied and (2) rejecting each approach and
      method not applied. That way, the valuation analyst will best achieve the purpose
      and objective of the health care intangible asset valuation.

PMID- 23971140
TI  - Reasons to value the health care intangible asset valuation.
AB  - There are numerous individual reasons to conduct a health care intangible asset
      valuation. This discussion summarized many of these reasons and considered the
      common categories of these individual reasons. Understanding the reason for the
      intangible asset analysis is an important prerequisite to conducting the
      valuation, both for the analyst and the health care owner/operator. This is
      because an intangible asset valuation may not be the type of analysis that the
      owner/operator really needs. Rather, the owner/operator may really need an
      economic damages measurement, a license royalty rate analysis, an intercompany
      transfer price study, a commercialization potential evaluation, or some other
      type of intangible asset analysis. In addition, a clear definition of the reason
      for the valuation will allow the analyst to understand if (1) any specific
      analytical guidelines, procedures, or regulations apply and (2) any specific
      reporting requirement applies. For example, intangible asset valuations prepared
      for fair value accounting purposes should meet specific ASC 820 fair value
      accounting guidance. Intangible asset valuations performed for intercompany
      transfer price tax purposes should comply with the guidance provided in the
      Section 482 regulations. Likewise, intangible asset valuations prepared for
      Section 170 charitable contribution purposes should comply with specific
      reporting requirements. The individual reasons for the health care intangible
      asset valuation may influence the standard of value applied, the valuation date
      selected, the valuation approaches and methods applied, the form and format of
      valuation report prepared, and even the type of professional employed to perform
      the valuation.

PMID- 23971141
TI  - Considering the health care entity C corporation conversion to tax pass-through
      entity status.
AB  - The double taxation of C corporation income from operations and from the ultimate
      sale of its assets makes the C corporation an inefficient tax status for many
      health care entities. At the time of this writing, the changes in the federal tax
      law that are scheduled to take effect in 2013 will increase this level of double
      taxation inefficiency. The owners of a C corporation practice can avoid the C
      corporation status tax inefficiency by converting the practice to either (1) S
      corporation status or (2) LLC status. The conversion of the health care C
      corporation to an S corporation may be accomplished without a current tax cost.
      However, the conversion of a health care C corporation to an LLC status can
      result in a current tax at both the corporation level and the shareholder level.
      Nonetheless, the current conversion tax cost may be less than the future tax cost
      (1) of operating the practice as a C corporation and incurring double taxation at
      what may be higher tax rates or (2) of incurring the higher tax cost (or reduced
      price) on the ultimate disposition of the practice assets and the attendant
      double taxation of the appreciation in the value of the practice assets. Since
      individual income tax rates on qualifying dividends from C corporations and on
      capital gains are currently at very low rates, this may be a good time for C
      corporation practice owners to consider the costs and benefits of a conversion to
      either S corporation status or LLC status. The practice owners should consult
      with their accounting, legal, and valuation advisors in order to consider all of
      the costs and benefits of a possible corporate tax status conversion. An
      estimation of both the costs and benefits of the corporate tax status conversion
      depends on the concluded fair market values of the medical practice, dental
      practice, or other health care entity assets. And, that practice asset appraisal
      should encompass all of the practice assets, both tangible assets and intangible
      assets.

PMID- 23971142
TI  - Health information technology impact on productivity.
AB  - Managers work to achieve the greatest output for the least input effort, better
      balancing all factors of delivery to achieve the most with the smallest resource
      effort. Documentation of actual health information technology (HIT) cost savings
      has been elusive. Information technology and linear programming help to control
      hospital costs without harming service quality or staff morale. This study
      presents production function results from a study of hospital output during the
      period 2008-2011. The results suggest that productivity varies widely among the
      58 hospitals as a function of staffing patterns, methods of organization, and the
      degree of reliance on information support systems. Financial incentives help to
      enhance productivity. Incentive pay for staff based on actual productivity gains
      is associated with improved productivity. HIT can enhance the marginal value
      product of nurses and staff, so that they concentrate their workday around
      patient care activities. The implementation of electronic health records (EHR)
      was associated with a 1.6 percent improvement in productivity.

PMID- 23971143
TI  - Microcap pharmaceutical firms: linking drug pipelines to market value.
AB  - This article examines predictors of the future market value of microcap
      pharmaceutical companies. This is problematic since the large majority of these
      firms seldom report positive net income. Their value comes from the potential of
      a liquidity event such as occurs when a key drug is approved by the FDA. The
      typical scenario is one in which the company is either acquired by a larger
      pharmaceutical firm or enters into a joint venture with another pharmaceutical
      firm. Binary logistic regression is used to determine the impact of the firm's
      drug treatment pipeline and its investment in research and development on the
      firm's market cap. Using annual financial data from 2007 through 2010, this study
      finds that the status of the firm's drug treatment pipeline and its research and
      development expenses are significant predictors of the firm's future stock value
      relative to other microcap pharmaceutical firms.

PMID- 23971144
TI  - [Relaunch of "Kinderkrankenschwester"].

PMID- 23971145
TI  - [Prevention of sudden infant death].

PMID- 23971146
TI  - [Cystic fibrosis - a childhood illness grows up].

PMID- 23971147
TI  - [In-line filter between perfusor pump and venous catheter provides a trouble-free
      infusion flow].

PMID- 23971148
TI  - [Rufaida Al-Aslamiya - the first muslim nurse].

PMID- 23971149
TI  - [Addiction and violence in immigrants].

PMID- 23971150
TI  - [Central venous catheter: risk of infection in pediatric patients].

PMID- 23971151
TI  - [Wheelchairs for Sarajevo - rehaKind members support mobility aids for
      disadvantaged children].

PMID- 23971152
TI  - [Position of the Catholic Nursing Society e.V. on "advanced nursing practice in
      Germany, Austria and Switzerland"].

PMID- 23971153
TI  - [Protecting the hearts of children from heat].

PMID- 23971154
TI  - Sensitivity/specificity: straw men, red herrings, and dental politics.

PMID- 23971155
TI  - The role of interprofessional education in the management of temporomandibular
      and sleep disorders.

PMID- 23971156
TI  - Headache and insomnia: their relation reviewed.
AB  - OBJECTIVE: Headache and insomnia are both very common and burdensome complaints
      worldwide. Numerous articles have been written on the relation between them, but
      the number of scientific articles is limited. The purpose of this review is to
      summarize the current scientific literature and analyze it in light of the nature
      of the headache-insomnia relation. METHODS: An extensive literature search was
      conducted using the terms, headache, migraine, insomnia, sleep, sleep
      deprivation, and sleep loss, on the search engines PubMed, ScienceDirect,
      Medline, and Google Scholar. A total of twelve research articles were found,
      discussing the relation of insomnia to headache in general, tension-type
      headache, migraine, and chronic headache. The majority of the studies are cross
      sectional but two are longitudinal. RESULTS: The studies suggest an association
      between headache and insomnia but an asymmetrical one, with headache being more
      associated with insomnia than the other way around. Therefore, in the association
      of headache and insomnia, other factors associated with headache or migraine
      probably play a role, as well. CONCLUSION: As insomnia appears to be a risk
      factor for headache or migraine onset, insomnia patients should probably be
      routinely evaluated for headache. As it also seems a risk factor for increased
      headache frequency, in particular in tension headache and migraine, patients with
      these conditions should probably be routinely treated for insomnia, if present,
      as part of their overall management.

PMID- 23971157
TI  - Effect of a maxillary appliance in an adult with obstructive sleep apnea: a case
      report.
AB  - Patients who arrive at the dental office with a diagnosis of obstructive sleep
      apnea (OSA) are often managed with a mandibular advancement device (MAD).
      However, the use of MADs has been associated with temporomandibular joint (TMJ)
      issues. The authors describe a case report of a 64-year-old male who was treated
      with a novel, maxillary oral appliance. The baseline sleep study indicated an
      apnea-hypopnea index (AHI) of 25.6/hour with 28 episodes of snoring, and 30.9
      oxygen desaturation events/hour. The patient wore the maxillary oral appliance
      for 10-12 hours/day and night. The midpalatal screw mechanism of the appliance
      was advanced once per week for six months. By the end of this time, the minimum
      intra-premolar width increased from 27 mm to 30 mm; the minimum intramolar width
      increased from 35 mm to 37 mm, and the AHI dropped to < 5/hour. During this phase
      of treatment, the episodes of snoring decreased to 18, and the oxygen
      desaturation events also decreased to 5.5/hour. After a total of 14 months, the
      AHI remained at < 5/hour, the episodes of snoring decreased further to 12, and
      the oxygen desaturation events decreased to 5.2/hour. Therefore, by achieving a >
      80% decrease in the AHI, less snoring and an improvement in oxygen saturation
      after 14 months, the use of a maxillary oral appliance appears to have reached
      resolution of OSA in an adult male.

PMID- 23971158
TI  - Measurement of mandible movements using a vernier caliper--an evaluation of the
      intrasession-, intersession- and interobserver reliability.
AB  - The aim of this study was to evaluate the intrasession-, intersession-, and
      interrater reliability of a vernier caliper measurement of mandible movements.
      The authors calculated the intrasession, intersession-, and interrater
      reliability using a plastic caliper for important mandibular parameters. All
      intraclass-correlation-coefficients (ICC) are at least moderately accurate,
      especially the values for intrasession- and intersession reliability, which were
      excellent. Only the interrater reliability shows greater fluctuations. Whereas
      the mouth opening, protrusion, and the tooth positions are reliably correct, the
      same was not applicable to the side movements. The lateral movement measurements
      were highly variable. This did not apply to other movements. Patient compliance
      is important along with a different mouth-opening angle. It is possible to
      generate a variable laterotrusion to both sides. The caliper investigated is a
      fast, simple, and inexpensive tool for daily work.

PMID- 23971159
TI  - Muscular activity in class III dentofacial deformity.
AB  - Individuals with Class III dentofacial deformities exhibit morphological changes
      and myofunctional adaptations, and an accurate diagnosis is essential for
      treatment planning. The purpose of this study was to evaluate the electrical
      activity of the masseter, temporal, and suprahyoid muscles in subjects with Class
      III dentofacial deformities, assessing electromyographic characteristics using
      functional tests. The research group consisted of 20 subjects with Class III
      dentofacial deformities and indications for surgical-orthodontic treatment. The
      control group consisted of 10 individuals presenting a good maxilla and mandible
      relationship. Electrical activities of the masseter and temporal were recorded
      during isometric contraction and maximal isometric contraction. The suprahyoid
      and masseter were assessed during maximal mouth opening and swallowing of saliva.
      Isometric contraction and maximal isometric contraction analysis showed less
      potential in the research group, with a significant difference regarding the
      masseter muscle in isometric contraction. In maximal isometric contraction, an
      increase in electrical activity in both groups was observed; it remained lower
      for the research group, but with no significant difference. With regard to
      symmetry, significant differences among the groups were observed only for the
      left masseter in the research group, as well as during isometric contraction.
      There was no significant difference found regarding maximal mouth opening. During
      swallowing of saliva, there was a high percentage of abnormal electromyographic
      tracings for both groups. This finding was not expected for the control group.
      The study found some changes in muscular activity in Class III dentofacial
      deformities, characterized by lower potential in the masseter muscle during
      isometric contractions. No other peculiarities were found that could contrast
      either group.

PMID- 23971160
TI  - Clinical study on the comparison of masticatory efficiency and jaw movement
      before and after temporomandibular disorder treatment.
AB  - In this clinical study, pre- and post-rehabilitation changes in intraborder
      mandible movements, chewing cycles, masticatory efficiencies, and borders of the
      chewing area of patients with unilateral muscular disorders (MD) (n = 20) or
      unilateral disc derangement disorders (DDD) (n = 20) of temporomandibular
      disorder (TMD) were observed and compared with healthy individuals with full
      dentition (n = 20) (48 female, 12 male; mean age: 28). The MD patients received
      stabilization splints and the DDD patients, anterior positioning splints for six
      weeks. Symptoms, such as muscle pain, TMJ pain, headache, chewing difficulty, and
      maximum mouth opening, showed significant improvements after splint therapy for
      both MD (p = 0.000) and DDD (p = 0.000) patients, but lateral excursion and
      protrusion were not significantly changed (p > 0.05). Chewing efficacy and
      chewing cycles improved significantly (p < 0.05) in both the MD (p < 0.05) and
      DDD (p < 0.05) groups, but only the MD group was comparable to the control group
      after treatment. Pre- and post-rehabilitation chewing cycles along the frontal
      plane on both sides in the MD group were similar to the control group.
      Considering the majority of the improvements in the diagnostic measures, patients
      with MD and DDD may benefit from occlusal splint therapy.

PMID- 23971161
TI  - Effects of affective picture viewing on postural control in healthy male
      subjects.
AB  - Emotion theory holds that unpleasant events prime withdrawal actions, whereas
      pleasant events prime approach actions. Recent studies have suggested that
      passive viewing of emotion-eliciting images results in postural adjustments. The
      main objective of this research was to investigate the effects of emotional
      inputs on the postural control. Ten healthy young adults looked at a series of
      emotion-eliciting images while standing on a force plate. The images were taken
      from the International Affective Picture System (IAPS). The posture-stabilometric
      parameters were statistically analyzed (RM ANOVA on Ranks). The results showed
      that the emotional inputs might influence body balance.

PMID- 23971162
TI  - Combined palliative and anti-inflammatory medications as treatment of
      temporomandibular joint disc displacement without reduction: a systematic review.
AB  - The aim of this study was to evaluate the efficacy of self-care combined with
      anti-inflammatory medications in the treatment of temporomandibular joint (TMJ)
      pain associated with disc displacement without reduction (DDWOR). A systematic
      review of randomized clinical trials was done by the authors. The databases
      searched were Medline (1966 to July 2012); EMBASE (1980 to July 2012); and LILACS
      (from 1982 to July 2012). The review authors independently assessed trials for
      eligibility and methodological quality and also extracted all data. The data was
      double-checked for accuracy. There was no language restriction in the searches of
      EMBASE, PubMed, and LILACS databases, or in the manual search. The risk of bias
      and the heterogeneity of the studies taken into consideration were assessed. Two
      studies, randomizing 175 patients, were included in this review. The first study
      (n = 106) compared the following interventions: medical treatment,
      rehabilitation, arthroscopic surgery with postoperative rehabilitation, or
      arthroplastic surgery with post-operative rehabilitation. The second study (n =
      69) compared the use of nonsteroidal anti-inflammatory medications and self-care
      instructions, nonsteroidal anti-inflammatory medications, occlusal splint, and
      mobilization therapy. The third group received no treatment; patients were only
      informed of their prognosis. There is no sufficient evidence regarding efficacy
      and safety of the palliative treatments associated with anti-inflammatory versus
      other treatments, or absence of treatment on pain reduction in patients with TMJ
      DDWOR.

PMID- 23971163
TI  - Eagle's syndrome: treatment by intraoral bilateral resection of the ossified
      stylohyoid ligament. A review and report of two cases.
AB  - The complexities of Eagle's syndrome are examined according to anatomical,
      historical, clinical, and treatment aspects. There appears to be little
      correlation between the extent, form, and size of the anomalies of the styloid
      process and the stylohyoid ligament and the predictability of patients with
      related symptoms. Surgical treatment and the advantages and disadvantages of each
      surgical approach (intra- and extraoral) are discussed. The probable causes of
      enlargement of the styloid process and ossification of the stylohyoid ligament
      are addressed. Two cases of Eagle's syndrome are presented: one unilateral and
      the other bilateral. An intraoral modified surgical technique is presented.

PMID- 23971164
TI  - Lung cancer imaging in 2012: updates and innovations.

PMID- 23971165
TI  - The new classification of lung adenocarcinomas: implications for pathologists and
      radiologists.
AB  - The present manuscript is a summary of two lectures which were given respectively
      by B. Weynand and G.R. Ferretti. The new classification of lung adenocarcinomas
      has changed the view of the radiologists and the pathologists especially
      regarding the former bronchiolo-alveolar carcinoma (BAC). The aim of this paper
      is to correlate radiological and histopathological images according to the 2011
      classification for lung adenocarcinoma proposed by the International Association
      for the Study of Lung cancer, the American Thoracic Society and the European
      Respiratory Society and to draw attention to the way these lesions can be
      approached preoperatively.

PMID- 23971167
TI  - Invasive staging of the mediastinum.
AB  - Staging of patients with lung cancer provides accurate information on the extent
      of disease and guides the choice of treatment. Non-invasive imaging techniques
      are safe, however these imaging techniques have limited accuracy in detection of
      mediastinal lymph node metastases. The American College of Chest Physicians
      guidelines for lung cancer staging recommend that patients with abnormal lymph
      nodes on CT or PET, or centrally located tumors without mediastinal LNs, should
      undergo invasive staging. Mediastinal nodal sampling has traditionally been
      performed by cervical mediastinoscopy. However, with the development of
      endoscopic needle aspiration techniques such as endobronchial ultrasound (EBUS)
      to guide transbronchial needle aspiration (TBNA) and endoscopic ultrasound (EUS),
      the diagnostic algorithm for lung cancer is changing.

PMID- 23971166
TI  - Update in non small-cell lung cancer staging.
AB  - Significant progress has been made with the introduction of the TNM-7 staging
      system for non-small cell lung cancer (NSCLC). Constituting the first major
      revision in 12 years, the seventh edition of NSCLC TNM (TNM-7) is based on the
      recommendations from the International Association for the Study of Lung Cancer
      (IASLC) Lung Cancer Staging Project of 2007. This new TNM iteration includes a
      subset analysis on SCLC and carcinoid tumors. A thorough understanding of its
      principles by the radiologist is helpful to increase efficiency and to improve
      communication with the referring clinicians.

PMID- 23971168
TI  - Whole body PET-CT: M staging in non small-cell lung cancer.
AB  - FDG PET has been used for years in the diagnosis and recurrence of non small cell
      lung cancer (NSCLC). It has an important impact on patient management, and its
      coupling with CT for immediate fusion allows immediate localization and
      characterization of uptake. This article reviews the role of FDG PET-CT in the
      staging of NSCLC for the detection of metastatic disease.

PMID- 23971169
TI  - Contribution of MRI in lung cancer staging.
AB  - Major advances in the WB-MRI in the initial evaluation and follow-up of patients
      with lung cancer have been performed in recent years. Multicentric studies using
      different magnet systems are necessary to confirm these promising results.

PMID- 23971170
TI  - Percutaneous ablation of malignant thoracic tumors.
AB  - Lung cancer is the leading cause of death related to cancer. Fifteen to thirty
      percent of patients with a localized lung cancer are actually inoperable as they
      present with poor general condition, limited cardiopulmonary function, or a too
      high surgical risk. Therefore, minimally invasive treatments are needed and
      percutaneous ablation seems an attractive option. Thermal ablation can be
      performed by delivering heat (radiofrequency, microwave, laser) or cold
      (cryotherapy) through a needle inserted into the tumor under CT guidance. The
      ideal lesion is less than 2 or 3 cm in diameter. Success of percutaneous thermal
      ablation appears to be close to those of surgery for localized lung cancer.
      Nevertheless studies are still needed to definitely assess the role of ablation
      compared to other emerging techniques, as stereotactic radiotherapy as well as
      potential synergy with other treatments.

PMID- 23971171
TI  - 4D PET-CT guided radiation therapy.
AB  - Tremendous technological progress in the field of imaging and computation have
      been revolutionizing radiotherapy of non-small cell lung cancer (NSCLC). Tumor
      biology can now be characterized by functional imaging for modifying treatment
      management and dose delivered in better accordance with the radiobiology of solid
      tumors and normal tissues. Specific radiation therapy (RT) strategies can further
      address the tumor motion issue, ensuring optimal tumor coverage with small safety
      margins.

PMID- 23971172
TI  - Dosimetry: which dose for screening, diagnosis and follow-up?
AB  - The question of which dose for screening, diagnosing ad follow-up of pulmonary
      nodules is a permanent issue for radiologists and radiotherapists. The proposed
      dose values for 2013 reflect the possibilities of the latest CT generations, from
      2010 or later and include all technical novelties such as iterative
      reconstructions, automatic tube potential selection, and latest detectors. As the
      technology is constantly evolving, these parameters are susceptible to lower
      every year.

PMID- 23971173
TI  - Screening for lung cancer by imaging: the Nelson study.
AB  - The NELSON trial is the first randomised lung cancer screening trial in which
      pulmonary nodule management is based on volumetry. This led to considerably less
      false-positive referrals compared to other lung cancer screening trials, with
      very high negative predictive values found in the first and second screening
      rounds. Mortality results are still pending, but the knowledge already gained in
      the NELSON trial and its side-studies provide valuable information in the field
      of screening for lung cancer.

PMID- 23971174
TI  - Recist and beyond.
AB  - The role of imaging in the evaluation of tumor response is expanding rapidly. The
      current response evaluation criteria in solid tumors (RECIST) based on anatomical
      changes suffers from many limitations related mainly to the inter- and intra
      observer variability to delineate the tumoral edges. Consequently, there is a
      need to update and integrate the RECIST criteria beyond the classical anatomical
      changes with other more sophisticated methods using three-dimensional and
      functional criteria. The goal of this paper is to review the current criteria of
      RECIST measurements (RECIST 1.1) with their limitations and to evaluate the
      emerging solutions available with the new imaging techniques like PET-CT.

PMID- 23971175
TI  - Assessment of lung tumor response by perfusion CT.
AB  - Perfusion CT permits evaluation of lung cancer angiogenesis and response to
      therapy by demonstrating alterations in lung tumor vascularity. It is advocated
      that perfusion CT performed shortly after initiating therapy may provide a better
      evaluation of physiological changes rather than the conventional size assessment
      obtained with RECIST. The radiation dose,the volume of contrast medium delivered
      to the patient and the reproducibility of blood flow parameters remain an issue
      for this type of investigation.

PMID- 23971176
TI  - A midline sagittal brain view depicted in Da Vinci's "Saint Jerome in the
      wilderness".
AB  - It is estimated that around the year 1480 Leonardo da Vinci painted Saint Jerome
      in the Wilderness, representing the saint during his years of retreat in the
      Syrian dessert where he lived the life of a hermit. One may interpret Leonardo's
      Saint Jerome in the Wilderness as St. Jerome practicing self-chastisement with a
      stone in his right hand, seemingly punching his chest repeatedly. The stone, the
      lion and a cardinal's hat are conventionally linked to the saint. A skull was
      also almost always present with the image of the saint symbolically representing
      penance. With careful analysis of the painting one can identify the skull which
      is hidden in an arc represented as a lion's tail. The image is of a hemicranium
      (midline sagittal view) showing the intracranial dura, including the falx and
      tentorium, and venous system with the sinuses and major deep veins. This may have
      been the first time when the intracranial sinuses and the major deep venous
      vessels were illustrated.

PMID- 23971177
TI  - Peritoneal carcinomatosis and prostatic cancer: a rare manifestation of the
      disease with an impact on management.

PMID- 23971178
TI  - Variations of the hepatic artery.

PMID- 23971179
TI  - Duodenal duplication cyst complicated by hemorrhage.

PMID- 23971180
TI  - Pelvic girdle enthesitis in spondyloarthritis.

PMID- 23971181
TI  - Active and structural lesions of the sacroiliac joints in spondyloarthritis.

PMID- 23971182
TI  - Leiomyosarcoma of the great saphenous vein.

PMID- 23971183
TI  - Pseudomyxoma peritonei due to mucinous adenocarcinoma of the appendix.

PMID- 23971184
TI  - Skull base bone hyperpneumatization.

PMID- 23971185
TI  - Congenital azygos pseudocontinuity with right lower intercostal vein.

PMID- 23971186
TI  - Changes in expression of calbindin 28 kDa in the small intestine of red kidney
      bean (Phaseolus vulgaris) lectin-treated suckling piglets.
AB  - Calbindin (CB) is a calcium binding protein playing a role in calcium uptake and
      anti-apoptotic cellular protection. The expression of CB was
      immunohistochemically studied in the small intestine of normal and red bean
      kidney lectin-treated suckling piglets. In the duodenum and jejunum (but not
      ileum) of lectin-treated animals overexpression of CB was noted in chromogranin A
      immunoreactive (CgA-IR) neuroendocrine (NE) cells. In both control and
      experimental group a small population of CB-IR NE cells exhibited the presence of
      somatostatin (but not serotonin, histamine or CRF). After the lectin treatment,
      an increased (however not statistically significant) immunoreactivity to CB was
      found in a small subpopulation of neurons of outer submucous (but not inner
      submucous and myenteric) plexus. It is suggested that there is a functional
      interaction between lectin administration and CB-expression in the porcine small
      intestine. Future studies will be needed to clarify this processes.

PMID- 23971187
TI  - The effect of respiratory diseases on serum lactate dehydrogenase and its
      isoenzyme patterns in calves.
AB  - In this study we examined the serum activity of lactate dehydrogenase (LDH) and
      its isoenzyme patterns in 28 calves of a lowland black spotted breed and its
      crossbreeds at the age of 2-6 months suffering from clinically noticeable
      manifested respiratory diseases--bronchopneumonia (BRD Group). As a control group
      we used 35 clinically healthy calves of the same age, breed and nutrition
      (Healthy Group). The sick calves did not show clinical signs or pathological
      lesions on other organ systems. The results found in sick calves showed a
      significantly higher total activity of LDH than in clinically healthy animals (P
      < 0.01). The mean activity of LDH was 2012 U/I in healthy calves and in calves
      with respiratory diseases 2529 U/1. The differences in all LDH isoenzyme patterns
      between both groups of animals were significant (P < 0.001) and in calves with
      respiratory diseases are characterized by a marked increase of the LDH 1 fraction
      and a decrease in the proportion of the other four LDH isoenzymes. Our results
      differ from those observed and presented in respiratory diseases in human
      medicine or in sheep. The explanation for the obtained results in calves and the
      determination of their diagnostic significance needs further studies and
      investigations using more animals with various severity of clinical signs and
      pathological changes, including analysis and determination of lactate
      dehydrogenase isoenzyme patterns in healthy and affected cattle lung tissue.

PMID- 23971188
TI  - Dexamethasone, but not meloxicam, suppresses proliferation of bovine CD25+ CD4+
      and CD25- CD4+ T cells.
AB  - Recently, we found that dexamethasone caused a depletion of CD25- CD4+ T cells,
      but it increased the number of CD25highCD4+ and CD25lowCD4+ T cells. We also
      determined meloxicam-induced increase in the number of CD25highCD4+ T cells. In
      view of this, and taking into consideration the latest reports indicating that
      meloxicam shows an anti-proliferative effect on bovine peripheral blood
      mononuclear cells, it was considered purposeful to determine the effect of both
      drugs on proliferation of bovine CD25highCD4+, CD25lowCD4+ and CD25- CD4+ T
      cells. Flow cytometry analysis and 5-bromo-2'-deoxyuridine incorporation assay
      were applied to detect the cell proliferation. It was demonstrated that
      dexamethasone, but not meloxicam, significantly reduced cell proliferation within
      all three evaluated CD4+ T cell subpopulations. Thus, the depletion of CD25- CD4+
      T cells by treatment with dexamethasone can partly be the effect of the anti
      proliferative action of the drug, however, dexamethasone-induced increase in the
      number of CD25highCD4+ and CD25IowCD4+ T cells cannot be the result of enhanced
      proliferation of these cells.

PMID- 23971189
TI  - Apoptosis of granulocytes and lymphocytes in peripheral blood in rabbits infected
      with haemagglutinating and non-haemagglutinating antigenic variants of the RHD
      (rabbit haemorrhagic disease) virus.
AB  - This paper attempts to study the dynamics of apoptosis of granulocytes and
      lymphocytes in peripheral blood in rabbits infected with haemagglutinating (Vt97,
      Triptis, Hartmannsdorf) and non-haemagglutinating (Pv97, 9905 RHDVa) antigenic
      variants of the RHD virus. The pathogenicity of those antigenic variants was also
      assessed by recording the mortality of the infected animals. The animals were
      infected with antigenic variants and blood was sampled at hour 0, 4, 8, 12, 24,
      36 p.i. and the percentage of apoptotic granulocytes and lymphocytes was measured
      with the use of flow cytometry. The results of the study showed that apoptosis is
      included during RHDV infection, as the number of apoptotic granulocytes and
      lymphocytes increases throughout the experiment; depending on the antigenic
      variant, apoptosis joins in at 4-8-12 h p.i. and lasts until 24-36 h p.i.
      Furthermore, the mortality of rabbits infected with the examined strains of RHD
      virus varied from 30% to 100%. This study performed for the first time in this
      manner, indicates the importance of apoptosis during infection with the RHD
      virus.

PMID- 23971190
TI  - Effect of cortisol on neurophysin I/oxytocin and peptidyl glycine-alpha-amidating
      mono-oxygenase mRNA expression in bovine luteal and granulosa cells.
AB  - Cortisol stimulates the synthesis and secretion of oxytocin (OT) from bovine
      granulosa and luteal cells, but the molecular mechanisms of cortisol action
      remain unknown. In this study, granulosa cells or luteal cells from days 1-5 and
      11-15 of the oestrous cycle were incubated for 4 or 8 h with cortisol (1 x 10(
      5), 1 x 10(-7) M). After testing cell viability and hormone secretion (OT,
      progesterone, estradiol), we studied the effect of cortisol on mRNA expression
      for precursor of OT (NP-I/OT) and peptidyl glycine-alpha-amidating mono-oxygenase
      (PGA). The influence of RU 486 (1 x 10(-5) M), a progesterone receptor blocker
      and inhibitor of the glucocorticosteroid receptor (GR), on the expression for
      both genes was tested. Cortisol increased the mRNA expression for NP-I/OT and PGA
      in granulosa cells and stimulated the expression for NP-I/OT mRNA in luteal cells
      obtained from days 1-5 and days 11-15 of the oestrous cycle. Expression for PGA
      mRNA was increased only in luteal cells from days 11-15 of the oestrous cycle. In
      addition, RU 486 blocked the cortisol-stimulated mRNA expression for NP-I/OT and
      PGA in both types of cells. These data suggest that cortisol affects OT synthesis
      and secretion in bovine ovarian cells, by acting on the expression of key genes,
      that may impair ovary

PMID- 23971191
TI  - Chicken amyloid arthropathy: serum amyloid A, interleukin-1beta, interleukin-6,
      tumour necrosis factor-alpha and nitric oxide profile in acute phase (12th hour).
AB  - Acute phase response (APR) is part of the early defense system, which is
      triggered by different stimuli including, infection, trauma, stres, inflammation
      and neoplasia. The APR complex is a reaction which induces homeostasis and
      recovery. In this research, serum amyloid A (SAA), interlaukin (IL)-1beta, IL-6,
      tumour necrosis factor alpha (TNF-alpha) and nitric oxide (NO) levels were
      measured 12 hours following injection. For this purpose, Thirty-two 5 weeks old
      laying chicken were allocated into four groups and intra-articular injections of
      Freund's adjuvant were used to induce amylod arthropathy in Groups II, III and
      IV. Vitamin A in group II, and methylprednisolone in group IV were added to
      enhance and to reduce the severity of amyloidosis, respectively. At the end of
      the research, it was observed that TNF-alpha and NO increased significantly (P <
      0.05) in vitamin A and methylprednisolone groups whereas SAA decreased
      significantly (P < 0.05) in all groups. It was also observed that IL-6 increased
      (P < 0.05) in vitamin A group and decreased in all other gorups however, IL-1beta
      decreased in vitamin A and methylprednisolone groups, while it was increased in
      the control group. The results of this study suggest that there is a positive
      correlation between serum TNF-alpha levels in acute and chronic phase in chickens
      with amyloid arthropathy.

PMID- 23971192
TI  - Quality of milk of cows in the first lactation vs. presence of anti-Ostertagia
      antibodies in their milk.
AB  - Invasions of gastrointestinal nematodes in dairy cows may affect animals
      productivity. The most frequently detected internal parasite of dairy cattle is
      Ostertagia ostertagi. The objective of this study was to determine O. ostertagi
      invasion extensiveness in selected herds of dairy cattle, with special
      consideration to cows being in the first lactation, and to analyze the milk yield
      and contents of basic constituents of milk originating from sero-positive cows.
      Five herds of dairy cattle (403), with different populations of cows, were
      selected for the study. Invasion extensiveness in particular herds was determined
      and ranged from 11.9% to 27.27%. Cows being in the first lactation, the udder
      milk of which was shown to contain anti-O. ostertagi antibodies, were producing
      on average 470 kg of milk annually less than cows being in the same lactation
      period. The analysis of results did not confirm the statistical significance of
      this difference, likewise it did not demonstrate any statistically significant
      differences in contents of fat, protein and dry matter. Despite a lack of the
      statistical significance a producer suffers great economic losses. The conducted
      study proves that the occurrence of O. ostertagi invasion in herds of dairy
      cattle is a global problem and that it affects cost-effectiveness of milk
      production.

PMID- 23971193
TI  - Interleukin-1beta stimulates early myogenesis of mouse C2C12 myoblasts: the
      impact on myogenic regulatory factors, extracellular matrix components, IGF
      binding proteins and protein kinases.
AB  - The purpose of the study was to examine the mechanisms important for early
      myogenesis in mouse C2C12 myogenic cells exposed to interleukin-1beta. Cyclin A
      and cyclin B1 were increased by interleukin-1beta (1 ng/ml), but the level of
      cyclin D1 and total DNA content was unaffected. Fusion index and the rate of
      protein synthesis was increased in the presence of IL-1beta, but these effects
      were limited to 3-day-treatment. IL-1beta increased the level of MyoD, myogenin
      and MHC on the 3rd day of differentiation, without altering the content of the
      active form of myostatin, as well as it augmented the level of fibronectin,
      integrin beta1 and full length 100 kDa form of ADAM12. IL-1beta caused a decrease
      in IGFBP-4 and IGFBP-6 levels and a marked increase in IGFBP-5. The
      phosphorylation of PKB and ERK1/2 and the cellular content of p38 were elevated
      by IL-1beta. We conclude that the myogenic effect of IL-1beta was limited to the
      onset of myoblast fusion and was associated with: i) increase in the level of
      myogenic transcription factors i.e. MyoD and myogenin expression, ii)
      modification of extracellular matrix assembly and signaling, manifested by an
      increase in fibronectin, integrin-beta1 and ADAM12 content, iii) drop in IGFBP-4
      and IGFBP-6, and an increase in IGFBP-5, that could alter the local IGF-1
      bioavailability, and iv) increase in phosphorylation of PKB and ERK1/2, and the
      expression of p38 kinase, leading to activation of intracellular pathways
      essential for myogenic differentiation.

PMID- 23971194
TI  - Complete mitochondrial genome of wild aurochs (Bos primigenius) reconstructed
      from ancient DNA.
AB  - Extinct aurochs (Bos primigenius), accepted as the ancestor of domestic cattle,
      was one of the largest wild animals inhabiting Europe, Asia and North Africa. The
      gradual process of aurochs extinction finished in Poland in 1627, were the last
      recorded aurochs, a female, died. Some aspects of cattle domestication history
      and the distribution of aurochs genetic material among modern cattle breeds still
      remain unclear. Analyses of ancient DNA (aDNA) from bone sample deliver new
      genetic information about extinct wild aurochs as well as modern cattle
      phylogeny. DNA was extracted from a fragment of aurochs fossil bone found in the
      Pisz Forest, Poland. The sample was radiocarbon-dated to about 1500 yBP. The aDNA
      was used for Whole Genome Amplification in order to form a DNA bank. Auroch
      mitochondrial DNA sequences were amplified using sets of 41 primers overlapping
      the whole mtDNA, cloned and sequenced. The sequence of the whole mitochondrial
      genome was reconstructed and deposed in GenBank [GenBank:JQ437479]. Based on the
      phylogenetic analyses of the Bovine mitochondrial genomes, a phylogenetic tree
      was created. As expected, the tree clearly shows that the mtDNA sequence of the
      analyzed PWA (Polish Wild Aurochs) individual belongs to haplogroup P. In the
      course of the comparative mtDNA analysis we identified 30 nucleotide marker
      positions for haplogroup P and nine unique PWA differences compared to the two
      remaining haplotype P representatives. Our analysis provides the next step to the
      reconstruction of the demographic history of this extinct but still exciting
      species.

PMID- 23971195
TI  - Cytoprotective effect of silybin against lasalocid-induced toxicity in HepG2
      cells.
AB  - Lasalocid is an ionophore coccidiostatic agent frequently used in poultry. Its
      extensive use causes the formation of residues in edible tissues and eggs which
      may pose a risk to consumers. Silybin is the main compound extracted from the
      herb milk thistle Silybum marianum and its hepatoprotective effect has been
      reported in literature. The aim of the study was to compare lasalocid and silybin
      cytotoxic effects followed by their combined use in HepG2 cell line. A
      cytoprotective effect resulting from the interaction of both pharmacologically
      active substances was measured. In this study, an MTT test, coomassie brillant
      blue binding test, and LDH release test determined the effective concentration
      (EC50) of the compounds. The isobolograms and combination index were used to
      assess the nature of interaction. The lowest EC50-value for lasalocid was
      established via the MTT test. This study revealed a lack of silybin cytotoxic
      effect on the cells. Co-actions of the two drugs led to a significant decrease of
      lasalocid cytotoxicity. The isobolograms and combination index showed a
      remarkable antagonistic effect in the course of silybin and lasalocid
      interaction. The results indicate that silybin revealed a cytoprotective effect
      when incubated with lasalocid since its cytotoxic impact on HepG2 cells has been
      significantly diminished.

PMID- 23971196
TI  - Production and characterization of egg yolk antibodies against bovine alimentary
      tract pathogens.
AB  - Aim of the study was to evaluate the effect of immunization of hens with bovine
      vaccines (C, R, T) on the course of IgY antibodies production against selected
      bovine E. coli strains, rota- and coronaviruses in egg yolk in farm conditions.
      The hens (40 individuals per group) were vaccinated twice, subcutaneously in four
      week interval and eggs were harvested once a week. Control group consisted of
      eggs sampled from non-vaccinated hens located in neighbouring cages. The antibody
      activity was measured by ELISA. All used vaccines induced the rise of IgY
      antibody in egg yolks. Based on the duration and the highest level of IgY
      antibody against bovine alimentary tract pathogens C vaccine was further used in
      next two trials for vaccination of 1000 hens each time. Double immunization seems
      to be enough in mounting response against examined pathogens for several weeks.
      Immunization with C vaccine allowed to harvest eggs with satisfactory levels of
      E. coli, rotavirus and coronavirus IgY antibodies which may be used to evaluate
      their protective effect by oral administration in calves.

PMID- 23971197
TI  - Imidazole-induced contractility of vascular smooth muscle cells in the presence
      of U-73122, ODQ, indomethacin and 7-nitroindazole.
AB  - The aim of the study was to assess the impact of modulating factors on vascular
      smooth muscle cells reactivity. Vascular resistance was induced by the
      administration of increasing concentrations of imidazole. The experiments were
      performed on isolated and perfused tail artery of Wistar rats (weight 250 g - 350
      g). Rats were been narcotized by urethane (intraperitoneal injection) at a dose
      of 120 mg/kg, stunned and then sacrificed by cervical dislocation. In the
      following investigation classical pharmacometric methods were used. Relationships
      between concentration-response curves (CRCs) for imidazole observed in the
      presence of ODQ [(1H-(1,2,4)oxadiazolo-[4,3-a]quinoxalin-1-one)], 7-nitroindazole
      and indomethacin were analyzed. Imidazole-induced contractility of vascular
      smooth muscle cells was independent from alpha-adrenergic receptors and PLC
      activity. Reactivity of VSMCsinduced by imidazole, was significantly changed in
      the presence of ODQ and 7-nitroindazole.

PMID- 23971198
TI  - Influence of microflora composition on safety and colour parameters of "kumpia
      wieprzowa" during ripening.
AB  - The aim of this study was to define the influence of microbiological activity on
      the safety (microflora composition, biogenic amine amount) and colour of "kumpia
      wieprzowa" during the 3-month ripening period. The study included the amount of
      aerobic bacteria, yeast, lactobacilli rods, coagulase-negative cocci, pH and
      colour parameters as well as the content of nitrates (V) and (III), biogenic
      amines and amino acids. The lactobacilli and cocci constituted the predominant
      microflora of the ready-to-eat product (4.9-5.2 and 5.2-5.4 log cfu/g,
      respectively), although further mesophilic bacteria identification revealed the
      presence of numerous aerobic, aerotolerant and anaerobic species, mostly gram
      positive, spore- and non-spore-forming. The absence of 2-phenylethylamine and
      putrescine and the low level of tryptamine (2.5 mg/kg) at the beginning of the
      ripening as well as the increase of tyramine and spermine amounts from 11.5 and
      2.7 to 21.9 and 4.0 mg/kg, respectively during the treatment, denoted the good
      quality of raw meat used and dynamic growth of the desired acidifying and
      denitrifying microorganisms. The development of the coagulase-negative cocci
      population corresponded with the a* and C* colour parameters and the nitrate
      (III) content increase, the final result of which was 26.9, 27.5 as well as 19.4
      mg/kg. The content of nitrates (V) and (III) was optimal to obtain a non-cured,
      safe and suitably coloured, long-term ripened meat product.

PMID- 23971199
TI  - Plasmid profile analysis and evaluation of antibiotic susceptibility of
      Staphylococcus aureus strains isolated from table chicken eggs.
AB  - The aim of this study was to isolate and characterize Staphylococcus aureus
      bacteria present on the shell surfaces and in the contents of chicken eggs,
      taking into account their phenotypic properties, antibiotic susceptibility
      patterns, and the presence of plasmid DNA. The study included 90 table chicken
      eggs from laying farms situated in the vicinity of Lublin. A total of 105
      bacterial strains identified as Staphylococcus were isolated from the material,
      of which 18 (17.14%) were of the species Staphylococcus aureus. All 18 S. aureus
      strains were found to be resistant to at least one of the antibiotics tested,
      while some (55.55%) showed resistance to five or more of the 17 therapeutic
      agents. The greatest number of strains showed resistance to erythromycin
      (66.66%), tetracycline (66.66%), oxytetracycline (61.11%), penicillin G (50%),
      and amoxicillin (44.44%). The plasmid profile analysis of the S. aureus strains
      made it possible to evaluate the dependence between antibiotic susceptibility and
      the presence of plasmids in particular isolates. The results showed that plasmids
      in various quantities and of varying molecular weights were isolated from 17 of
      the strains. Most often isolated were small plasmids, of 5.6 kb--from 11 of the
      S. aureus strains (61.11%), 2.5 kb--from 9 strains (50%), 4.1 kb--from 8
      (44.44%), and 4.6 kb--from 7 (38.88%) of the strains.

PMID- 23971200
TI  - The effects of experimental administration of low doses of zearalenone on the
      histology of ovaries in pre-pubertal bitches.
AB  - The experiment involved 30 clinically healthy Beagle bitches aged approximately
      70 days with an initial body weight of approximately 8 kg. The animals were
      randomly divided into two experimental groups (EI and EII) and a control group of
      10 animals each. Group EI was administered 50 microg of body weight
      zearalenone/kg per os for 42 days, group EII received 75 microg of body weight
      zearalenone/kg per os for 42 days, and the control group was administered
      placeboper os for 42 days. The bitches were ovariectomized at the end of the
      treatment period for anatomopathological examination. At the same time,
      peripheral blood samples were collected for endocrinological analyses (17beta
      estradiol and progesterone). Administartion of zearalenone particularly higher
      doses, resulted in the hyperestrogenism degeneration and atrophy of ovarian cells
      and tissues with accompanying edema and blood extravasation, leading to increased
      17beta-estradiol concentrations and an insignificant decrease in progesterone
      levels.

PMID- 23971201
TI  - The novel effect of hCG administration on luteal function maintenance during the
      estrous cycle/pregnancy and early embryo development in the pig.
AB  - Two independent experiments were performed on cyclic (Experiment I) and pregnant
      (Experiment II) gilts to examine the effect of human Chorionic Gonadotropin (hCG)
      administration on day 12 of the estrous cycle/pregnancy on ovarian and
      endometrial secretory function. Animals were divided into hCG Group (injection of
      750 IU hCG) and Control Group (injection of saline). In Experiment I, the
      prolonged lifespan of the corpus luteum (CL), extended progesterone (P4)
      production (P < 0.05) and delayed luteolysis were found. In hCG Group increased
      ratio of PGE2:PGFM during 12 hrs period on day 15 (P < 0.05) of the estrous cycle
      was observed. In both experiments, higher concentrations of E2 in hCG treated
      gilts (P < 0.05) on days 14-15 of the estrous cycle/pregnancy were found. In
      Experiment II, hCG injection did not affect P4, PGE2 and PGFM concentrations in
      blood plasma, but reduced the number of resorbed embryos on day 30 of pregnancy.
      In the pregnant hCG treated gilts the immunostaining against von Willebrand
      Factor (vWF) demonstrated an enhanced (P < 0.05) angiogenesis in CLs and
      endometrium. Furthermore, the flow cytometry revealed an increased (P < 0.05)
      viability of cells in CLs of hCG Group. An augmented expression of Steroidogenic
      Acute Regulatory Protein (STAR; P < 0.05) and LH/hCG receptor mRNA (P < 0.05) in
      CLs of hCG Group were observed, but an elevated concentration of protein was
      confirmed only for STAR (P < 0.05). Our studies revealed, for the first time,
      that administration of hCG affects PGE2:PGFM ratio during the estrous cycle as
      well as the development of conceptuses through enhanced angiogenesis and
      decreased luteal apoptosis in early pregnant pigs.

PMID- 23971202
TI  - The effect of different dietary levels of vitamin E and selenium on antioxidant
      status and immunological markers in serum of laying hens.
AB  - The effect of different dietary levels of selenium (Se) and vitamin E on egg
      production, the antioxidant status and the immune system response of hens was
      investigated in the current study. A total of 32 Lohman Brown hens were divided
      into four groups and were fed diets with 5% of soybean oil and two levels of Se
      (0.15 and 0.30 mg/kg) and vitamin E (30 and 60 mg/kg). During 10 weeks of
      experimental feeding, the body weights of hens and egg production were similar in
      all dietary treatments, but a higher Se content of diets contributed to a
      significant increase in egg weight. A higher vitamin E level significantly
      increased alpha-tocopherol concentrations (2.71 vs. 2.05 microg/mL, p = 0.001),
      superoxide dismutase (SOD) activity (43.3 vs. 39.9 U/mL, p = 0.049) and the
      ferric reducing ability of serum (FRAP) (123.0 vs. 105.7 micromol/L, p = 0.029).
      A higher Se content increased the concentrations of ascorbic acid (0.309 vs.
      0.073 microg/L, p = 0.001), retinol (1.48 vs. 1.15 microg/mL, p = 0.001) and
      alpha-tocopherol (2.86 vs. 1.90 microg/mL, p = 0.001), the activity levels of
      catalase (3.40 vs. 2.98 U/L,p = 0.010) and SOD (43.4 vs. 30.8 U/mL, p = 0.040) as
      well as the total antioxidant status (TAS) of serum (0.38 vs. 0.28 mmol/L, p =
      0.026). There were no significant differences in the concentrations of tumor
      necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) between treatments, while
      a higher vitamin E content of diets increased serum immunoglobulin A (IgA)
      concentrations (370.6 vs. 321.3 microg/mL, p = 0.026). Higher dietary levels of
      vitamin E and Se increased the serum concentrations of retinol (1.66 vs. 2.20
      microg/mL, p = 0.013) and a-tocopherol (3.33 vs. 1.71, p = 0.014), but they had
      no effect on the other physiological parameters. It is recommended that the
      levels of both supplements, Se and vitamin E, be increased in laying hen diets as
      they have a beneficial effect on the serum concentrations of retinol and alpha
      tocopherol.

PMID- 23971203
TI  - The effect of T-2 toxin on percentages of CD4+, CD8+, CD4+ CD8+ and CD21+
      lymphocytes, and mRNA expression levels of selected cytokines in porcine ileal
      Peyer's patches.
AB  - The immune system is one of the main toxicity targets of the T-2 toxin. In view
      of scant research data demonstrating the effect of T-2 on cellular and humoral
      responses in gut-associated lymphoid tissue (GALT), this study set out to
      investigate the effects of chronic exposure to low doses of the T-2 toxin (200
      microg T-2 toxin kg(-1) feed) on percentages of CD4+ and CD8+ T lymphocytes,
      CD4+/CD8+ double-positive T lymphocytes, CD21+ B cells, and IL-2, IFN-gamma, IL-4
      and IL-10 mRNA expression levels in porcine ileal Peyer's patches. The
      investigated material comprised ileum sections sampled from piglets (aged 8-10
      weeks, body weight of 15-18 kg) on days 14, 28 and 42 of the experiment. After 42
      days of exposure to T-2, a significant drop in the quantity of the IL-10 product
      was observed (R = 0.94; S.E. 0.49-0.79; p < 0.001). A gradual decrease in the
      amount of IL-4 and IFN-gamma cytokine transcripts was found throughout the
      experiment, but the reported trend was not significant. On experimental days 14
      and 42, a significant increase in the percentage of CD8+ T lymphocytes was
      observed in comparison with the control (p = 0.04 and p = 0.05, respectively),
      whereas on day 28, a significant decrease in the percentage of the above
      subpopulation was noted (p = 0.00). The percentage of CD21+ B cells in the
      experimental group decreased steadily in comparison with the control, and the
      observed drop was significant on days 28 and 42 (p = 0.06 and p = 0.00,
      respectively). On days 14 and 28, the percentages of CD4+ and CD8+ T lymphocytes
      were lower in the experimental animals than in the control group, and the drop
      reported on day 28 was statistically significant (p = 0.03).

PMID- 23971204
TI  - Identification of Propionibacteria to the species level using Fourier transform
      infrared spectroscopy and artificial neural networks.
AB  - Fourier transform infrared spectroscopy (FTIR) and artificial neural networks
      (ANN's) were used to identify species of Propionibacteria strains. The aim of the
      study was to improve the methodology to identify species of Propionibacteria
      strains, in which the differentiation index D, calculated based on Pearson's
      correlation and cluster analyses were used to describe the correlation between
      the Fourier transform infrared spectra and bacteria as molecular systems brought
      unsatisfactory results. More advanced statistical methods of identification of
      the FTIR spectra with application of artificial neural networks (ANN's) were
      used. In this experiment, the FTIR spectra of Propionibacteria strains stored in
      the library were used to develop artificial neural networks for their
      identification. Several multilayer perceptrons (MLP) and probabilistic neural
      networks (PNN) were tested. The practical value of selected artificial neural
      networks was assessed based on identification results of spectra of 9 reference
      strains and 28 isolates. To verify results of isolates identification, the PCR
      based method with the pairs of species-specific primers was used. The use of
      artificial neural networks in FTIR spectral analyses as the most advanced
      chemometric method supported correct identification of 93% bacteria of the genus
      Propionibacterium to the species level.

PMID- 23971205
TI  - Morphology and immunohistochemical characteristics of the pterygopalatine
      ganglion in the chinchilla (Chinchilla laniger, Molina).
AB  - Histological and histochemical investigations revealed that the pterygopalatine
      ganglion (PPG) in the chinchilla is a structure closely connected with the
      maxillary nerve. Macro-morphological observations disclosed two different forms
      of the ganglion: an elongated stripe representing single agglomeration of nerve
      cells, and a ganglionated plexus comprising smaller aggregations of neurocytes
      connected with nerve fibres. Immunohistochemistry revealed that nearly 80% of
      neuronal cell bodies in PPG stained for acetylcholine transferase (CHAT) but only
      about 50% contained immunoreactivity to vesicular acetylcholine transporter
      (VACHT). Many neurons (40%) were vasoactive intestinal polypeptide (VIP)
      positive. Double-staining demonstrated that approximately 20% of the VIP
      immunoreactive neurons were VACHT-negative. Some neurons (10%) in PPG were
      simultaneously VACHT/nitric oxide synthase (NOS)- or Met-enkephaline (Met
      ENK)/CHAT-positive, respectively. A small number of the perikarya stained for
      somatostatin (SOM) and solitary nerve cell bodies expressed Leu-ENK- and galanin
      immunoreactivity. Interestingly about 5-8% of PPG neurons exhibited
      immunoreactivity to tyrosine hydroxylase (TH). Intraganglionic nerve fibres
      containing immunoreactivity to VACHT-, VIP- and Met-ENK- were numerous, those
      stained for calcitonin gene related peptide (CGRP)- and substance P (SP)- were
      scarce, and single nerve terminals were TH-, GAL-, VIP- and NOS-positive.

PMID- 23971206
TI  - Blood antioxidant enzymes (SOD, GPX), biochemical and haematological parameters
      in pigs naturally infected with porcine reproductive and respiratory syndrome
      virus.
AB  - Porcine reproductive and respiratory syndrome (PRRS) has become one of the most
      economically important diseases for the swine industry worldwide. The objective
      of the study was to determine selected blood antioxidant enzymes (glutathione
      peroxidase (GPX), superoxide dismutase (SOD)), biochemical and haematological
      parameters in PRRS positive and negative pigs of three different categories,
      mainly to test oxidative stress hypothesis in pigs naturally infected with PRRS
      virus. Ninety PRRS positive and 90 PRRS negative pigs were included in the study.
      The presence of PRRS was confirmed by serological detection of antibodies against
      PRRS virus (PRRSV) and detection of PRRS viral RNA by RT-PCR. Pigs were further
      divided into three groups of 30: piglets just before weaning (weaners), fatteners
      and finishers. Blood samples for determining selected blood parameters were
      collected from the vena cava cranialis. Significantly (P < 0.05) higher
      activities of SOD in weaners and fatteners and of GPX in weaners were determined
      in PRRS positive pigs than in corresponding groups of PRRS negative pigs. In
      contrast, significantly (P < 0.05) lower GPX activity was observed in finishers
      of PRRS positive pigs than in the corresponding group of PRRS negative pigs.
      Concentrations of serum total protein in PRRS positive weaners and fatteners were
      significantly (P < 0.05) higher than those found in PRRS negative pigs.
      Leukopenia was observed in all three groups of PRRS positive pigs. It has been
      demonstrated, for the first time, that oxidative stress might be increased in
      PRRSV naturally infected pigs, especially in weaners.

PMID- 23971207
TI  - Pharmacokinetics of orally administered simvastatin in turkeys.
AB  - The aim of the present study was to determine the pharmacokinetics of simvastatin
      (SIM) administered orally in 6-week-old turkeys at a single dose of 2 mg/kg b.w.
      The SIM concentrations in plasma were determined by validated HPLC-MS/MS method.
      Mean (+/- SD; n = 10) values of pharmacokinetic parameters evaluated were as
      follows: Cmax = 0.49 +/- 0.21 ng/ml, t(max) = 1.6 +/- 1.1 h, AUC(0-infinity) =
      1.08 +/- 0.57 h x ng/ml, t1/2kel = 2.14 +/-1.3 h and MRT = 3.08 +/- 1.52 h. The
      results indicate that the SIM is absorbed from the gastrointestinal tract of
      turkeys; however, achieved plasma level is lower compared to those observed in
      mammals.

PMID- 23971208
TI  - Reduction of prevalence of persistent BVDV infection in cattle herds by long-term
      vaccination program (preliminary clinical study).
AB  - Effectiveness of long-term anti-BVDV vaccination program in reducing prevalence
      of persistent BVDV infection in cattle herds was evaluated in seven years
      observational study (2005-2011). Among three seropositive dairy cattle herds
      (within herd seroprevalence 100%, confirmed by ELISA Herd Check BVDV Ab, IDEXX,
      Sweden) vaccination program based on inactivated vaccine (cytopathic strain 5960)
      was commenced in 2007 in two herds and continued till 2010. In the years 2007
      2011 all calves aged 2-12 weeks in all three herds were tested yearly with RT-PCR
      in order to detect persistently infected individuals. For the entire study period
      true prevalence of BVDV persistent infection was significantly lower in
      vaccinated than in non-vaccinated herd. This may imply the role of long-term
      vaccination program in reducing prevalence of persistent BVDV infection in cattle
      herds.

PMID- 23971209
TI  - The serum protein electrophoretic pattern and acute phase protein concentrations
      in calves with chronic respiratory diseases.
AB  - The aim of this study was to evaluate the serum protein electrophoretic pattern
      and the concentrations of acute phase proteins (haptoglobin, serum amyloid A, and
      fibrinogen) in 28 calves with clinical signs of chronic respiratory diseases and
      36 healthy calves as a control group. In sick calves we found significantly
      higher serum concentrations of total proteins (P < 0.001), lower concentrations
      of albumin (P < 0.001) and marked shift in the concentrations of the most of
      protein fractions with significantly higher values of alpha1-, beta1-, beta2-,
      and gamma-globulins (P < 0.001 and P < 0.01). The affected calves had
      significantly higher values of haptoglobin, serum amyloid A, and fibrinogen as
      well (P < 0.05, P < 0.001 and P < 0.001, respectively).

PMID- 23971210
TI  - Influence of mutation in cj0183 and cj0588 genes for colonization abilities of
      Campylobacter jejuni in Caco-2 cells using confocal laser scanning microscope.
AB  - The cj0183 and cj0588 genes identified in the Campylobacter jejuni NCTC 11168
      genome encode proteins with homology to virulence factors found in other
      bacteria. Previous studies showed that single mutation in the cj0183 gene does
      not affect adhesion of C. jejuni to the Caco-2 cell line whereas protein encoded
      by cj0588 is involved in adherence to the Caco-2 cells. In the presented study
      differences in invasion index were observed between mutants in both genes and
      single mutation of cj0588 in 81116 and 81-176 C. jejuni strains This fact
      indicates that Cj0183 protein might play some role in invasion of bacteria into
      host cells.

PMID- 23971211
TI  - Toxin-producing fungi on feed grains and application of yeasts for their
      detoxification.
AB  - The research deals with the contamination of feeding crops with fungi, producing
      mycotoxins and use of selected yeasts for detoxification. The thin-layer
      chromatography and ELISA methods were applied for the analysis of fungal
      secondary metabolites. The results showed a high rate of the grain contamination
      with fungi, mainly from genera Penicillium, Fusarium, Aspergillus and Alternaria.
      Some of the fungal strains produced 6-9 toxic compounds. The novelty of the study
      was the application of the yeast strains in detoxification of aflatoxins,
      zearalenon and deoxynivalenol in feed.

PMID- 23971212
TI  - Effect of age and stage of lactation on whey protein content in milk of cows of
      different breeds.
AB  - The aim of the study was to determine the effect of age of cows, i.e. subsequent
      lactation and stage of lactation, on bioactive whey protein content in milk of
      dairy cows of six primary breeds kept in Poland. In all cases the significant
      correlations between lactoferrin concentration in milk and stage of lactation was
      stated. Its content gradually increased with the course of lactation but the
      changes in the content of this protein were highly dependent on breed of cows,
      what was indicated also by high interactions between breed and stage of
      lactation.

PMID- 23971213
TI  - Prosthetic reconstruction of broken canine teeth in dogs with use of cast metal
      posts.
AB  - Prosthodontic treatment, especially restorations of fractured teeth in small
      animals, has been the subject of many veterinary dental analyses in relation to
      techniques of endodontic treatment, preparation and cementation, as well as the
      general principles of prosthodontic treatment. The purpose of this paper is to
      present a previously undescribed method of all-in-one crown and root prosthetic
      restoration of fractured teeth in large dogs, together with a thorough analysis
      of the drawbacks, which may help veterinary dentists to use an evidence-based
      approach when deciding on the type of treatment for their patients with tooth
      fractures.

PMID- 23971214
TI  - Short-term whole body vibration exercise in adult healthy horses.
AB  - The purpose of this study was to analyze the acute effect of whole body vibration
      exercise (WBVE) on clinical parameters and blood values in horses. Seven horses
      were exposed to a 10 min WBVE at a frequency of 15-21 Hz. Clinical parameters and
      venous blood samples were taken before and directly after WBVE. Acute short-term
      WBVE produced a decrease in serum cortisol (p = 0.02) and creatine-kinase (p =
      0.02) values. Clinical parameters, hematology, fibrinogen, lactate, IGF-I, GGT,
      creatinine, myeloperoxidase activity and bone marker values were not
      significantly changed by WBVE. In adult sound horses WBVE was well tolerated and
      did not cause any sign of measured discomfort.

PMID- 23971215
TI  - Platelets--an important element of the immune system.
AB  - Platelets are anucleate cells derived from the megakaryocyte series, and have
      long been considered only as cells responsible for coagulation and the
      fibrinolysis process. However, recently more data shows that they are also
      effector cells in the inflammatory response and important elements of the
      immunological response. Platelets store and release many biologically active
      substances, including growth factors, cytokines and chemokines (tab. 1), which
      actively affect i.a. elements of the immune system, and thus become regulators of
      immunity and mediators of inflammatory response. Their impact on the immune
      system cells is also associated with the induction of leucocytes and progenitor
      cells to the site of pathogen permeation or vascular injury inflow, as well as
      endothelial cells. Interacting with neutrophils, monocytes and lymphocytes, they
      not only activate them, but also form platelet-leukocyte aggregates that
      immobilise pathogens and prevent their spreading. Furthermore, platelets are
      capable of absorbing pathogens, affecting anti-infection immunity of the system.
      It is also assumed that the presence of receptors on their surface, such as Toll
      like receptors (TLRs), affects their initiation and activity of the immunological
      response.

PMID- 23971216
TI  - Serum amyloid A as an indicator of health status in falcons.
AB  - Serum amyloid A (SAA) is used as an indicator of health status in many species.
      To investigate the possible use of SAA as a health indicator in falcons, SAA
      levels were measured in 259 falcons of varying species and health status. A
      significant increase (P < .001) in SAA concentrations was observed in falcons
      affected by inflammatory disease compared with healthy birds and birds with
      noninflammatory disease. Serum amyloid A concentrations ranged from 0.1 to 6.8
      mg/L (mean [SD], 3.4 +/- 1.4 mg/L) in the healthy group, from 0.8 to 8.5 mg/L
      (mean [SD], 4.0 +/- 3.1 mg/L) in the group with noninflammatory disease, and from
      2.3 to 137.5 mg/L (mean [SD], 47.7 +/- 29.7 mg/L) in the group with inflammatory
      disease. In birds with chronic pododermatitis or fungal pneumonia/airsacculitis,
      SAA levels remained significantly increased throughout the study period. These
      results indicate that SAA concentrations can be used in avian medicine to assess
      the health status of falcons and as a prognostic indicator of certain pathologic
      disease processes.

PMID- 23971217
TI  - Normal ocular parameters and characterization of ophthalmic lesions in a group of
      captive bald eagles (Haliaeetus leucocephalus).
AB  - Sixteen adult captive bald eagles (Haliaeetus leucocephalus) underwent a complete
      bilateral ocular examination to assess normal ocular parameters and describe
      ophthalmic lesions. Tear production was measured with the Schirmer tear test 1
      and intraocular pressure was measured with applanation tonometry. The menace
      response was normal bilaterally in 13 of 16 eagles. Two birds had normal menace
      responses despite having fundic lesions, and 2 birds with an inconsistent or
      absent menace response did not have appreciable ophthalmic lesions. Mean (SD)
      tear production was 14 +/- 2 mm/min (range, 8-19 mm/min). Mean intraocular
      pressure was 21.5 +/- 1.7 mm Hg (range, 15-26 mm Hg). At least 1 ocular lesion
      was present in 50% of examined eyes. Cataracts, the most common lesion observed,
      were present in 8 eyes of 5 birds. Three of 4 known geriatric birds were or had
      been affected with bilateral cataracts. Overall, ocular lesions are common in
      captive bald eagles, and cataracts appear to be more prevalent in geriatric bald
      eagles. An obvious positive menace response is present in most visual birds but
      may be absent in some eagles that are either normal or that do not have
      appreciable ophthalmic lesions. Applanation tonometry and the Schirmer tear test
      1 can be performed easily on adult bald eagles and provide reproducible results.

PMID- 23971218
TI  - Plasma protein electrophoresis in birds: comparison of a semiautomated agarose
      gel system with an automated capillary system.
AB  - Plasma agarose gel electrophoresis (AGE) is recognized as a very reliable
      diagnostic tool in avian medicine. Within the last 10 years, new electrophoresis
      techniques such as capillary zone electrophoresis (CZE) have emerged in human
      laboratory medicine but have never been investigated in birds. To investigate the
      use of CZE in birds and to compare it with AGE, plasma samples from 30 roosters
      (Gallus gallus), 20 black kites (Milvus migrans), and 10 racing pigeons (Columba
      livia) were analyzed by both AGE and CZE. For the 3 species studied, values
      determined by AGE and CZE were well correlated for albumin and beta and gamma
      fractions whereas other values differed significantly. Values for alpha-3
      fraction in the rooster, alpha-1 fraction in the black kite, and alpha fractions
      in the pigeon obtained by AGE were very well correlated with the prealbumin
      fraction values obtained by CZE. Repeatability and reproducibility appeared
      higher with CZE than with AGE. Although the interpretation of CZE electrophoresis
      patterns seems to produce results similar to those obtained with AGE, some
      proteins present in the alpha fraction measured with AGE migrated to the
      prealbumin fraction found with CZE. Although CZE requires the use of specific
      reference intervals and a much higher sample volume, this method has many
      advantages when compared with AGE, including better repeatability and
      reproducibility and higher analysis output.

PMID- 23971219
TI  - Comparison of fluid types for resuscitation in acute hemorrhagic shock and
      evaluation of gastric luminal and transcutaneous Pco2 in Leghorn chickens.
AB  - The objective of this study was to compare the effects of 3 different fluid types
      for resuscitation after experimentally induced hemorrhagic shock in anesthetized
      chickens and to evaluate partial pressures of carbon dioxide measured in arterial
      blood (Paco2), with a transcutaneous monitor (TcPco2), with a gastric
      intraluminal monitor (GiPco2), and by end tidal measurements (Etco2) under stable
      conditions and after induced hemorrhagic shock. Hemorrhagic shock was induced in
      40 white leghorn chickens by removing 50% of blood volume by phlebotomy under
      general anesthesia. Birds were divided into 4 groups: untreated (control group)
      and treated with intravenous hetastarch (haes group), with a hemoglobin-based
      oxygen carrier (hemospan group), or by autotransfusion (blood group). Respiratory
      rates, heart rates, and systolic arterial blood pressure (SAP) were compared at 8
      time points (baseline [T0]; at the loss of 10% [T10%], 20% [T20%], 30% [T30%],
      40% [T40%], and 50% [T50%] of blood volume; at the end of resuscitation [RES];
      and at the end of anesthesia [END]). Packed cell volume (PCV) and blood
      hemoglobin content were compared at 6 time points (T0, T50%, RES, and 1, 3, and 7
      days after induced hemorrhagic shock). Measurements of Paco2, TcPco2, GiPco2, and
      Etco2 were evaluated at 2 time points (T0 and T50%), and venous lactic acid
      concentrations were evaluated at 3 time points (T0, T50%, and END). No
      significant differences were found in mortality, respiratory rate, heart rate,
      PCV, or hemoglobin values among the 4 groups. Birds given fluid resuscitation had
      significantly higher SAPs after fluid administration than did birds in the
      control group. In all groups, PCV and hemoglobin concentrations began to rise by
      day 3 after phlebotomy, and baseline values were reached 7 days after blood
      removal. At T0, TcPco2 did not differ significantly from Paco2, but GiPco2 and
      Etco2 differed significantly from Paco2. After hemorrhagic shock, GiPco2 and
      TcPco2 differed significantly from Paco2. The TcPco2 or GiPco2 values did not
      differ significantly at any time point in birds that survived or died in any of
      the groups and across all groups. These results showed no difference in mortality
      in leghorn chickens treated with fluid resuscitation after hemorrhagic shock and
      that the PCV and hemoglobin concentrations increased by 3 days after acute
      hemorrhage with or without treatment. The different CO2 measurements document
      changes in CO2-values consistent with poor perfusion and may prove useful for
      serial evaluation of responses to shock and shock treatment.

PMID- 23971220
TI  - A technique for evisceration as an alternative to enucleation in birds of prey:
      19 cases.
AB  - Ocular trauma is common in birds of prey presented to wildlife clinics and
      rehabilitation centers. Enucleation is the procedure most commonly described for
      treatment of end-stage ocular disease or chronically painful eyes in birds;
      however, there are several disadvantages and risks to this procedure. While
      evisceration has been suggested as an alternative, it has not been described for
      multiple cases or with long-term follow-up data in birds of prey. This report
      details an evisceration technique performed in 5 captive birds of prey of 4
      different species (1 eastern screech owl [Megascops asio], 1 great horned owl
      [Bubo virginianus], 2 red-tailed hawks [Buteo jamaicensis], and 1 bald eagle
      [Haliaeetus leucocephalus]) with long-term follow-up information. In addition,
      this report describes 14 cases of free-living owls of 3 different species (1
      great horned owl, 4 barred owls [Strix varia], and 9 eastern screech owls) on
      which this technique was performed from 2004 to 2011 and which were subsequently
      released to the wild. Because of the limited risk of complications and the less
      severe disruption of facial symmetry, which may be particularly important in owls
      that are candidates for release to the wild, evisceration should be considered
      over enucleation in birds of prey that require surgical intervention for the
      management of severe sequelae to ocular trauma.

PMID- 23971221
TI  - Perforating foreign body in the ventriculus of an umbrella cockatoo (Cacatua
      alba).
AB  - A 4-year-old male umbrella cockatoo (Cacatua alba) with a history of ingestion of
      foreign material from chewing on a household appliance presented for lethargy,
      inappetance, and regurgitation of 2 days duration. Foreign bodies identified on
      radiograph included a wire 2 cm in length in the proventriculus, a wire 3 cm in
      length in the ventriculus, and several pieces of rubber and plastic throughout
      the gastrointestinal tract. Diagnosis of a perforating ventricular foreign body
      was made through plain and contrast radiography. The proventricular wire was
      removed endoscopically but endoscopic retrieval was not successful in locating
      the ventricular wire. A ventriculotomy was done to remove the wire, which had
      perforated the ventriculus cranially and imbedded into the parenchyma of the
      liver. The wire was extracted from the center of a large nonresectable granuloma
      that incorporated the left liver lobe. The bird recovered from surgery but died
      from complications 3 months later. Postmortem examination revealed localized
      coelomitis and hepatic necrosis associated with the perforation.

PMID- 23971222
TI  - Suspected cholecalciferol rodenticide toxicosis in avian species at a zoological
      institution.
AB  - Over a 2-month period, individual birds belonging to species in multiple avian
      families, including Bucerotidae, Sturnidae, Columbidae, Corvidae, and Anatidae,
      were presented to the Animal Care Center at the Phoenix Zoo for emergency medical
      care. Common clinical findings were subdued behavior, weight loss, and an
      inability to fly. Biochemical abnormalities commonly included high calcium and
      uric acid concentrations and high to high-normal phosphorus concentrations. In
      cases in which necropsies were done, mineralization of organs often was present,
      frequently of the kidneys and cardiovascular system. Because of the high calcium
      and phosphorus concentrations, mineralization of tissues, cases representing
      multiple avian species, and the recent addition of rodent bait boxes containing
      cholecalciferol to the zoo's pest control program, a presumptive diagnosis of
      cholecalciferol toxicosis was made. Treatment most commonly consisted of daily
      fluid diuresis. These cases demonstrate that, although cholecalciferol is
      considered unlikely to cause relay toxicosis, primary toxicosis still should be
      considered in cases with sudden onset of nonspecific signs when exposure to
      cholecalciferol was possible.

PMID- 23971223
TI  - Companion birds in early America.

PMID- 23971224
TI  - Veterinary medicine in Europe: issues and concerns.

PMID- 23971225
TI  - What is your diagnosis? Chronic severe nutritional osteodystrophy, or rickets.

PMID- 23971226
TI  - A closer look at the standards for nurse anesthesia practice.
AB  - As part of its ongoing work, the AANA's Practice Committee reviewed the Scope and
      Standards for Nurse Anesthesia Practice, particularly focusing on the Standards
      for Nurse Anesthesia Practice. Revisions and updates were made to the standards
      to ensure clarity and reflect current anesthesia practice. This article
      highlights several of the important revisions made to the Standards for Nurse
      Anesthesia Practice, specifically focusing on the importance of documentation,
      updates to Standard V-Patient Monitoring, and changes to other documents affected
      by the updates. This is not an exhaustive discussion of all changes made to the
      document. The updated Standards for Nurse Anesthesia Practice are presented in
      their entirety.

PMID- 23971227
TI  - The National Practitioner Data Bank: what CRNAs need to know.
AB  - As a nationwide flagging system, the National Practitioner Data Bank (NPDB)
      allows state licensing boards, hospitals, and other registered healthcare
      entities the ability to monitor practitioners through reporting and inquiry about
      the qualifications and competency of healthcare practitioners seeking clinical
      privileges where incompetence or unprofessional conduct could adversely affect a
      patient's welfare. Certified Registered Nurse Anesthetists are not exempt from
      being reported on or queried by registered reporting and querying entities. The
      NPDB warehouses data pertaining to adverse actions or medical malpractice
      payments taken against a practitioner. Based on the updated federal ruling
      published in the Federal Register regarding the NPDB and Section 1921 of the
      Social Security Act, the NPDB has expanded the definition of healthcare
      practitioners to include all healthcare practitioners as a means of protecting
      beneficiaries of the Social Security Act's healthcare programs. As such, nurse
      anesthetists should be aware of the additional reportable information that may be
      collected or disseminated based on the updated ruling pertaining to the NPDB.

PMID- 23971228
TI  - Emerging evidence in infection control: effecting change regarding use of
      disposable laryngoscope blades.
AB  - The purpose of this evidence-based project was to determine the perceptions of
      anesthesia providers regarding the use of disposable laryngoscope blades.
      Frequency of use, ease of use, and complications encountered when using the
      disposable blade were evaluated before and after an in-service program designed
      to increase the use of disposable blades. Participants completed an anonymous
      questionnaire about their knowledge and practice regarding disposable
      laryngoscope blades. Then they received an investigator-developed article to read
      about the best and most recent practices regarding disposable laryngoscope
      blades. The same anonymous questionnaire was completed 3 months later. Inventory
      of the disposable laryngoscope blades was collected before the project and 1 and
      3 months later. After the intervention, 25% of anesthesia providers described
      performance as their reason for not using the disposable laryngoscope blade,
      which was down from 60% at the project's start. Inventory showed a 23% increase
      in use of disposable laryngoscope blades after the intervention, which a single
      proportion Z test showed was statistically significant (Z = 2.046, P = .041).
      This evidence-based project shows that a change in practice was evident after
      dissemination of the best and most recent clinical evidence regarding
      laryngoscope blades, which should translate to improved patient outcomes.

PMID- 23971229
TI  - Palliative sedation in nursing anesthesia.
AB  - Palliative sedation is a technique of providing a sedative for end-of-life care
      to patients with intractable pain. The literature discusses the techniques and
      use of palliative sedation. Numerous articles have been written regarding the
      issues surrounding its use, but no literature has discussed the prescription or
      administration of palliative sedation by a nurse anesthetist. By understanding
      the concept and ethics involved in its use and providing nursing care that is
      theory based, the author argues that the involvement of nursing anesthesia is
      appropriate and within the scope of practice. Few other healthcare disciplines
      can provide the patient care and empirical knowledge that is imperative in the
      care of the dying patient. This article discusses the concept and ethics of
      palliative sedation and presents a case of providing palliative sedation to a
      terminally ill patient by an experienced nurse anesthetist. Palliative sedation
      should be understood, embraced, and utilized as an area of expertise suited for
      nursing anesthesia.

PMID- 23971230
TI  - Effects of ketamine on major depressive disorder in a patient with posttraumatic
      stress disorder.
AB  - Ketamine has been used in anesthesia for many years and in various environments
      with an acceptable safety margin. The side effects of hallucinations and paranoid
      thoughts need to be overcome for acceptance of ketamine infusion in mainstream
      psychiatry. In this case report, the anesthesia department was consulted because
      of familiarity with the medication and the ability to modulate unacceptable side
      effects with its use as is done in monitored anesthesia care. It is proposed that
      ketamine has potential for treatment of major depression associated with
      posttraumatic stress disorder (PTSD) in combat veterans. This patient, who had
      debilitating and treatment-resistant major depression and PTSD, was treated by
      intravenous infusion of ketamine and experienced substantial short-term
      resolution of symptoms.

PMID- 23971231
TI  - Anesthesia care team risk: considerations to standardize anesthesia technician
      training.
AB  - The anesthesia profession has produced voluminous research data on equipment and
      techniques leading to safer practices, but the lack of attention given to the
      inconspicuous role of anesthesia support personnel on the anesthesia care team
      may pose a risk to patient safety. It is questionable whether the skills of
      anesthesia support personnel who are trained on the job have kept up with an
      increasingly complex healthcare environment. Medical technology and demand for
      high-quality care will continue to escalate; patient safety will remain a top
      priority. Therefore, a definitive strategy to mitigate risk and ensure patient
      safety begins with strengthening the infrastructure of the anesthesia team.
      Formal education and certification may ensure that skill sets of anesthesia
      support personnel will uniformly advance with technology and standards of patient
      care.

PMID- 23971232
TI  - Thromboelastography-guided transfusion Therapy in the trauma patient.
AB  - This article presents thromboelastography (TEG) as an important assay to
      incorporate into anesthesia practice for development of evidence-based therapy of
      trauma patients receiving blood transfusions. The leading cause of death
      worldwide results from trauma. Hemorrhage is responsible for 30% to 40% of trauma
      mortality and accounts for almost 50% of the deaths occurring in the initial 24
      hours following the traumatic incident. On admission, 25% to 35% of trauma
      patients present with coagulopathy, which is associated with a sevenfold increase
      in morbidity and mortality. The literature supports that routine plasma-based
      routine coagulation tests, such as prothrombin time, activated partial
      thromboplastin time, and international normalized ratio, are inadequate for
      monitoring coagulopathy and guided transfusion therapy in trauma patients. A
      potential solution is incorporating the use of the TEG assay into the care of
      trauma patients to render evidence-based therapy for patients requiring massive
      blood transfusions. Analysis with TEG provides a complete picture of hemostasis,
      which is far superior to isolated, static conventional tests. The result is a
      fast, well-designed, and precise diagnosis enabling more cost-effective
      treatment, improved clinical outcome, accurate use of blood products, and
      pharmaceutical therapies at the point of care.

PMID- 23971233
TI  - Pathophysiology and management of angiotensin-converting enzyme inhibitor
      associated refractory hypotension during the perioperative period.
AB  - Hypertension is a common chronic condition in many patients requiring anesthesia.
      Pharmacologic therapy is a mainstay of treatment for hypertension, with
      angiotensin-converting enzyme (ACE) inhibitors being a frequently prescribed
      class of drugs. The American College of Cardiology and American Heart Association
      2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for
      Noncardiac Surgery provide information on many drug classes used in the treatment
      of hypertension; noticeably absent is a guideline for ACE inhibitors. Literature
      demonstrates that practice standards vary on whether ACE inhibitor regimens are
      continued or withheld during the preoperative period. When ACE inhibitor therapy
      is continued in patients undergoing general anesthesia, varying degrees of
      hypotension can be seen depending on confounding patient variables and the type
      of surgical procedure. In some instances, this hypotension can be refractory to
      traditional interventions such as administration of a fluid bolus, ephedrine, or
      phenylephrine. Vasopressin and methylene blue have been found to be effective
      treatments for ACE inhibitor-associated refractory hypotension. With the
      prevalence of hypertension and use of ACE inhibitors, anesthesia providers are
      likely to encounter refractory hypotension of this nature. The absence of
      guidelines regarding ACE inhibitors in the perioperative period contributes to a
      lack of consistency in practice.

PMID- 23971234
TI  - A study to determine the efficacy of controlled ovarian hyperstimulation regimen
      using a gonadotropin releasing hormone agonist versus antagonist in women of
      advanced reproductive age with varying degrees of oocyte reserve on outcome
      following in vitro fertilization-embryo transfer.
AB  - PURPOSE: To determine if the use of gonadotropin releasing hormone (GnRH)
      agonists (a) or antagonists (ant) allow better pregnancy rates when used in
      controlled ovarian hyperstimulation protocols in women of advanced reproductive
      age. Furthermore the study aimed to determine if the status of ovarian oocyte
      reserve has a confounding effect. MATERIALS AND METHODS: A 12-year retrospective
      review was performed on all in vitro fertilization-embryo transfer (IVF-ET)
      cycles in women aged 40-44. Pregnancy rates were determined according to whether
      a GnRH-a or GnRH-ant was used. The data were also stratified according to normal
      or low oocyte reserve. RESULTS: There was no significant difference in pregnancy
      rates according to whether a GnRH-a or GnRH-ant was used in women with normal
      oocyte reserve. Though a large majority of the women used a GnRH-ant, there was a
      9% live pregnancy rate vs 0% in the women using a GnRH-a. CONCLUSION: Since it is
      unlikely that a larger study will ever be conducted, it is probably wise to use a
      GnRH-ant for the controlled ovarian hyperstimulation regimen in women aged 40-44
      with diminished oocyte reserve.

PMID- 23971235
TI  - Defective oocytes are not a common cause of unexplained infertility as determined
      by evaluation of sharing oocytes between infertile donors and recipients.
AB  - PURPOSE: To determine if defective oocytes or sperm may be a common etiologic
      factor in unexplained infertility. MATERIALS AND METHODS: A retrospective
      comparison of fertilization rates and pregnancy rates from infertile donors with
      unexplained infertility trying to conceive with in vitro fertilization-embryo
      transfer (IVF-ET) and their respective recipients, who shared the other half of
      the oocytes with the recipient's male partner for financial compensation was
      performed. Pregnancy rates from donors and recipients were also compared to other
      donor recipient pairs sharing oocytes from infertile donors with tubal or male
      factor or financially-compensated donors providing oocytes to two recipients.
      RESULTS: Pregnancy rates from infertile donors with unexplained infertility were
      comparable not only to their respective recipients but to other donor/recipient
      pairs that received oocytes from donors with tubal or male factor or financially
      compensated donors. Fertilization rates were somewhat reduced in the infertile
      donors. CONCLUSIONS: Abnormal embryos resulting from an oocyte or sperm defect do
      not appear to be a common cause of unexplained infertility. The possibility does
      exist that sperm may be an etiologic factor in reduced fertilization potential,
      which not only could be obviated by conventional oocyte insemination, but could
      be further improved by intracytoplasmic sperm injection (ICSI).

PMID- 23971236
TI  - A comparison of clinical pregnancy rates and multiple gestation rates with 2 vs 3
      embryos transferred with pairs matched for embryo quality.
AB  - PURPOSE: To determine the impact of embryo quality on multiple birth rates.
      MATERIALS AND METHODS: A retrospective review of in vitro fertilization-embryo
      transfer (IVF-ET) cycles over ten years was performed. The data was stratified by
      number of embryos transferred (two vs three) and by percentage of embryos with <
      6 vs > or = 6 blastomeres. RESULTS: Pregnancy rates (PRs) increase with the
      greater number of embryos with a higher blastomere count. However transferring
      more embryos with less blastomeres does not lower the risk of multiple births.
      CONCLUSIONS: Couples should consult the table, e.g. presented here, so they can
      make their best choice of how many embryos to transfer considering the importance
      of a higher pregnancy rate vs the risk of the complication of multiple births.

PMID- 23971237
TI  - Placental and umbilical cord macroscopic changes associated with fetal and
      maternal events in the hypertensive disorders of pregnancy.
AB  - AIM: The purpose of this study was to identify placental and umbilical cord
      macroscopic changes and correlate them to maternal and fetal clinical events in
      hypertensive disorders of pregnancy (HDP). MATERIALS AND METHODS: The authors
      examined 150 placentas, 30 from each HDP group, totaling 120, and 30 from the
      control group. All placentas and umbilical cords were examined, recorded, and
      photographed. RESULTS: The mean placental weight in the control group (526.3 +/-
      95.6 g) was greater than in the HDP (435.5 +/- 43.1 g). Calciphylaxis was the
      most common macroscopic change found in the control and HDP groups in 27 (90%)
      and 118 cases (98.3%), respectively. DISCUSSION: Pregnant women with HDP were
      relatively younger. In addition, due to low blood flow seen in HDP, the
      macroscopic changes found included lower placental weight, calciphylaxis in the
      maternal surface, and fibrin in the fetal surface. Because of all complications
      associated, most women with HDP had preterm infants who developed respiratory
      problems and had shorter umbilical cords.

PMID- 23971238
TI  - Experience improves performance of hysterosalpingo-contrast sonography (HyCoSy):
      a comprehensive and well-tolerated screening modality for the subfertile patient.
AB  - PURPOSE: To investigate the clinical observations, provider experience, safety,
      and tolerance of the hysterosalpingo-contrast sonography (HyCoSy) procedure.
      MATERIALS AND METHODS: A retrospective study design in which data was collected
      from ninety-six subfertile women who underwent the HyCoSy procedure at the
      University of Louisville over a 16-month interval. RESULTS: Ninety-six HyCoSy
      procedures were performed by a single investigator and contained complete records
      for review. The authors observed significant decreases in the quantities of
      saline and air utilized per procedure over time (p < 0.0001 and p = 0.0001).
      Results from the HyCoSy studies were more often non-diagnostic or non-patent in
      women with a body mass index (BMI) > 30. Reported pain scores did not
      statistically differ over the course of the study interval. There were no
      procedure-related complications noted. CONCLUSION: The HyCoSy procedure is a
      timely and minimally invasive study that can be implemented in an office setting
      with minimal prior operator experience that improves over time.

PMID- 23971239
TI  - Evaluation of adhesions after laparoscopic myomectomy using the Harmonic Ace and
      the auto-crosslinked hyaluronan gel vs Ringer's lactate solution.
AB  - OBJECTIVE: To evaluate the efficacy of a crosslinked hyaluronic acid (HA) for the
      prevention of postsurgical adhesions after laparoscopic myomectomy using the
      Harmonic Ace. MATERIALS AND METHODS: Women 23-42 years of age who wished to
      conceive underwent laparoscopic myomectomy. As adhesion preventing agents,
      crosslinked HA gel was applied on the myometrial scar at the end of the surgery
      in Group A, whereas in Group B a Ringer's lactate solution was used in a
      prospective, observational study. Second-look mini-laparoscopy was performed 45
      60 days after surgery and the adhesions were assessed according to a site
      specific modified scoring. RESULTS: The incidence of postoperative adhesions was
      the same in both groups, but anatomically significant adhesions and site-specific
      modified score was significantly reduced in Group A compared to Group B control
      group (31.8% vs 54.6% and 1.05 +/- 1 vs 2.27 +/- 2.5, respectively). CONCLUSION:
      The use of auto-cross-linked HA gel confirms a protection on adhesion formation
      on myometrial wounds, although the degree of this effect appears to be weak. The
      absence of adnexa adhesions using the HA and a different uterine incision appear
      remarkable, although a larger number of patients is required to confirm the
      present findings.

PMID- 23971240
TI  - Relevance of thrombophilia and impact of office hysteroscopy on recurrent in
      vitro fertilization failures: a case series.
AB  - The study evaluated the validity of office hysteroscopy (OH) in 51 infertile
      women and whether congenital or acquired thrombophilia is more prevalent in women
      with recurrent IVF failures.

PMID- 23971241
TI  - Dihydrotestosterone may contribute to the development of migraine headaches.
AB  - PURPOSE: To evaluate the possibility that dihydrotestosterone (DHT) may play a
      role in the etiology of some people's migraine headaches. METHODS: Finasteride 5
      mg daily was given to a young woman with chronic migraines. RESULTS: The chronic
      migraine headaches almost completely disappeared shortly following therapy.
      However, symptoms returned shortly after stopping the finasteride due to dry
      eyes. CONCLUSIONS: DHT may be an etiologic factor in causing migraines since
      finasteride suppresses DHT secretion. Alternatively, the benefit could be related
      to some other property of finasteride possibly by increasing testosterone which
      may compete with estrogen at the blood vessel level.

PMID- 23971242
TI  - Colostrum in menopause effects on vaginal cytology/symptoms.
AB  - The aim of this study was to assess the effects of three weeks of daily colostrum
      cream on vaginal cytology and local symptoms related to menopause. Genito-urinary
      symptoms and cell morphology were analyzed at time 0 (T0) and after three weeks
      (16 +/- days since the end of treatment) at time 1 (T1). Dyspareunia, vaginal
      dryness, and maturation index (MI) reached a statistically significant difference
      between T0 and T1. The results proved to be an alternative treatment for vaginal
      distress caused by lack of hormones in patients in which hormonal treatment is
      contraindicated.

PMID- 23971243
TI  - Superselective uterine arterial embolization combined with transcatheter intra
      arterial methotrexate infusion in 40 cases with fallopian tube ectopic pregnancy.
AB  - PURPOSE: To evaluate the therapeutic results of superselective uterine artery
      infusion and embolization in 40 patients with fallopian tube ectopic pregnancy,
      and to explore the role of this minimally invasive treatment as an alternative to
      surgery. MATERIALS AND METHODS: Superselective catheterization of uterine artery
      through cannulation of femoral artery was achieved in 40 patients with fallopian
      tube ectopic pregnancy (EP). Location of the lesions involved feeding arteries
      and active bleeding were observed through angiography. Methotrexate (MTX) diluted
      in saline water was slowly infused into the target artery. Small gelatin spongy
      particles were used to embolize the uterine artery until its branches were
      totally obliterated. Follow-up was undertaken to observe the results of the
      treatment. RESULTS: Superselective uterine arterial infusion and embolization
      were successfully performed in all 40 patients without any related complications.
      Active bleeding in the peritoneum in 33 cases ceased soon after embolization. The
      embryos in 13 patients were confirmed to have died by ultrasound three days after
      the procedure. Beta-human chorionic gonadotropin ((beta-hCG) value dropped to
      below 15 IU/L at three to 21 days. Hemorrhage in the peritoneum dissolved after
      seven days in all cases. Mixed mass disappeared after one month.
      Hysterosalpingography was performed three months after the procedure in 19
      patients and patent fallopians were demonstrated in 16 patients. CONCLUSIONS:
      Superselective uterine arterial infusion and emboliztion is a minimally invasive
      procedure, which can be used to effectively treat EP by disabling the ectopic
      embryo and leaking arteries with the advantages of preserving the fallopian
      tubes.

PMID- 23971244
TI  - Sympathomimetic amines effectively control pain for interstitial cystitis that
      had not responded to other therapies.
AB  - PURPOSE: To further investigate the efficacy of treatment of interstitial
      cystitis that had been refractory to standard treatment with sympathomimetic
      amines. METHODS: Dextroamphetamine sulfate sustained release capsules up to 30 mg
      per day were prescribed in women with refractory painful bladder
      syndrome/interstitial cystitis in six new cases. The patients were carefully
      evaluated for relief of symptoms. RESULTS: All six women found marked relief in
      their painful bladder syndrome in a rather short length of time. The benefit
      persisted as long as the therapy was maintained. Temporary cessation resulted in
      prompt return of symptoms, but resumption of sympathomimetic amines again allowed
      good relief of bladder pain and related symptoms. CONCLUSIONS: Because of very
      few side-effects and no drug dependence in the dosage used, sympathomimetic
      amines should be considered for first-line therapy.

PMID- 23971245
TI  - Dyslipidemia is a persistent problem in puerperium with or without preeclampsia.
AB  - PURPOSE OF INVESTIGATION: To compare serum levels of triglycerides and
      cholesterol and the dyslipidemic factor (DLF): (triglycerides (mg/dl)/150) X
      (cholesterol (mg/dl)/200) among puerperal women with or without preeclampsia.
      MATERIALS AND METHODS: Three groups of puerperal women were formed: group A
      uncomplicated deliveries, group B deliveries complicated with preeclampsia that
      had not attended the Obstetric Intensive Care Unit (OICU); and group C puerperal
      women complicated with preeclampsia and that had attended the OICU. RESULTS: The
      authors studied a total of 47 puerperal women, 14 without complications, 11
      complicated with preeclampsia, and 22 complicated with preeclampsia requiring
      attention at the OICU. Thirteen (92.8%) puerperal women without complications and
      100% of puerperal women complicated with preeclampsia had triglycerides higher
      than 150 mg/dl at least three days post-delivery. Furthermore, six puerperal
      women without complications (42.8%), one puerperal woman complicated with
      preeclampsia (9%), and eight puerperal women complicated with preeclampsia
      requiring attention at the OICU (36.3%) had levels in crescendo. CONCLUSIONS:
      Hypertriglyceridemia is a persistent problem in puerperal women who suffered
      preeclampsia and the DLF could be a useful tool to evaluate a mixed lipemic
      state. Finally, preeclampsia and dyslipidemia might be considered as risk factors
      to develop chronic endothelial disease (CED).

PMID- 23971246
TI  - Low-dose estrogen and drospirenone combination: effects on metabolism and
      endothelial function in postmenopausal women with metabolic syndrome.
AB  - PURPOSE: Metabolic syndrome and endothelial dysfunction play a relevant role in
      the cardiovascular risk in post-menopause. The aim of the study was to assess the
      effects of a low-dose hemihydrate estradiol and drospirenone combination on
      cardiovascular risk parameters in postmenopausal women with metabolic syndrome.
      MATERIALS AND METHODS: Twenty-eight healthy women (group A) and 28 women with
      metabolic syndrome (group B) were treated with hemihydrate estradiol one mg +
      drospirenone two mg. At recruitment and after six months, clinical and laboratory
      parameters of metabolic syndrome were evaluated. Endothelial function was
      assessed measuring the flow-mediated dilatation of the brachial artery and the
      intima-media thickness of the common carotid artery. RESULTS: After six months an
      overall improvement of metabolism was observed in both groups reaching
      statistical significance for triglycerides, total cholesterolemia, and systolic
      pressure in group B. A trend to lower baseline flow-mediated dilatation was also
      found in group B. CONCLUSIONS: Drospirenone improves cardiovascular risk factors
      and does not impair endothelial function in menopausal women with metabolic
      syndrome.

PMID- 23971247
TI  - Maternal mortality in Serbia.
AB  - Maternal mortality related to obstetric events is still high today. The main
      components of reproductive health are evaluated. Early diagnosis of the obstetric
      risks can significantly reduce maternal mortality.

PMID- 23971248
TI  - Operative treatment of gynaecologic diseases in puberty: seven years of
      experience.
AB  - PURPOSE OF INVESTIGATION: The aim of this study is to present the incidence and
      surgical management of gynaecologic pathology in adolescence in the 1st
      Obstetrics and Gynecology Department of Aristotle University of Thessaloniki.
      METHODS: After a retrospective review of the medical records of over a seven year
      period (2004-2011), 32 adolescent patients with reported surgical gynaecologic
      procedures were identified and analysed. RESULTS: Fourteen out of the 16
      adolescents with ovarian masses (eight neoplastic and eight non-neoplastic) were
      treated by laparoscopy. Congenital anomalies were diagnosed in seven patients and
      only one of them was treated by laparotomy. The rest were surgically treated for
      uterine leiomyoma (1), ectopic pregnancy (2), pelvic abscess (1), mesosalpingeal
      cysts (2), mesenterian cyst (1) and investigation of chronic pelvic pain.
      DISCUSSION: Although benign ovarian cysts and congenital anomalies represent the
      major indication for operative treatment of gynaecologic diseases in puberty,
      laparoscopy and/or hysteroscopy should be the gold standard procedure after
      careful preoperative investigation.

PMID- 23971249
TI  - Eclampsia with neurological complications: a five-year experience of a tertiary
      centre.
AB  - PURPOSE: The neurological signs and symptoms in 107 pregnant women with eclampsia
      in the last five years at the Department of Obstetrics and Gynecology at the
      Yuzuncu Yil University School of Medicine are presented. MATERIALS AND METHODS:
      The medical records of 107 pregnant women with eclampsia in the Clinic of
      Obstetrics and Gynecology at the Yuzuncu Yil University consulted with neurology
      clinic from September 2005 to December 2010, were evaluated. RESULTS: The most
      common symptoms of the patients were seizure, headache, and seeing spots of
      light. Although neurologic examination was normal in 81 patients, 26 had
      pathological signs. The most common neurologic pathologic signs determined were
      alterations in consciousness. CONCLUSION: In eclamptic patients, brain scanning
      might reveal pathological results in spite of normal neurological examination.
      With neurological examination and brain scanning, it may be possible to diagnose
      and treat severe complications that may otherwise result in maternal mortality.

PMID- 23971250
TI  - Accuracy of the cytopathology, bacterioscopy, and vaginal flora culture.
AB  - INTRODUCTION: An over-population of vaginal microorganisms causing inflammatory
      processes renders it difficult to properly assess the cytopathological exam that
      aims to screen precedent cervical lesions. On the contrary, the occurrence of the
      microbial flora saprophyte does not influence correct cythodiagnosis. OBJECTIVE:
      To assess the composition of vaginal tract aerobic microorganisms of asymptomatic
      women in menacme and post-menopause, and to analyze the accuracy of
      cytopathologic, bacterioscopic exams, and culturing of the flora. METHODS: The
      women were first submitted to a focused anamnestic interrogatory and then
      submitted to gynecological exam. A sample of the vaginal fluid was collected with
      a culture swab and a smear was made on two glass slides for stained
      bacterioscopic exam (GRAM). The collection of material was then compiled in a
      cytopathologic smear analysis. All women signed the free and informed consent
      letter and the project was approved by the Ethics Research Board of Hospital Sao
      Paulo - UNIFESP. RESULTS: Bacterioscopy and culture proved to be better than the
      cytopathologic exam in featuring the bacilli and cocci. The bacterioscopy
      provided a better detection of the presence of bacilli (p < 0.001); no
      statistical difference was seen between both exams with respect to the detected
      cocci. The beta-hemolytic Streptococcus group was of significance in post
      menopausal women (p < 0.05). CONCLUSION: In this study, the bacterioscopic and
      culture exams of the vaginal fluid were more effective in assessing the vaginal
      flora and in the detection of bacilli, compared to the cytopathological exam.

PMID- 23971251
TI  - Comparison of hysterosonography and hysteroscopy for diagnosing perimenopausal
      bleeding.
AB  - This investigation was a prospective study performed at the Gynecological Clinic
      "Narodni Front" in Belgrade. In the investigated group, endometrial hyperplasia,
      endometrial polyp, and myoma were diagnosed as the most frequent causes of
      bleeding during perimenopause. The test group of patients was then subjected to
      hysterosonography in order to diagnose bleeding etiology, followed by
      hysteroscopy to confirm its etiology based on hysterosonography. Material was
      sent for histopathological analysis to definitely confirm the diagnosis. The aim
      of this study was to the compare the findings of hysterosonography and
      hysteroscopy to evaluate the sensitivity and efficacy of hysterosonography for
      diagnosing the etiology of uterine bleeding in perimenopausal women. In the
      diagnostics of submucosal myoma, endometrial hyperplasia, and endometrial polyps,
      hysterosonography has proven to be a good screening method. By its use for
      diagnosing intracavitary uterine pathology, and thus also the pathology of
      bleeding in perimenopausal women, in many cases hysteroscopy can be avoided. This
      is a method that is easy to perform, less invasive, less costly to perform, and
      is well-tolerated.

PMID- 23971252
TI  - Diagnosis value of hysteroscopy for chronic endometritis.
AB  - OBJECTIVE: To investigate the correlation of hysteroscopy in the diagnosis of
      chronic endometritis (CE) with histology and assess its reliability. MATERIALS
      AND METHODS: Two hundred eleven patients with CE diagnosed by hysteroscopy were
      selected as the case group, and 30 cases without endometritis diagnosed by
      hysteroscopy were selected as the control group. Hysteroscopy and endometrial
      biopsy were carried out in all patients with endometrial hyperplasia. RESULTS:
      Among 211 patients with CE diagnosed by hysteroscopy, 200 cases were confirmed
      histologically. There was a significant correlation (p < 0.001) between
      characterization of CE by hysteroscopy and pathological grading. In 173 cases
      (86.5%), both histological and hysteroscopic grading were consistent (Kappa value
      = 0.62). CONCLUSION: Hysteroscopy is reliable in diagnosing CE and it can assess
      clinical effectiveness of antibiotic therapy.

PMID- 23971253
TI  - The prevalence of phenotypic subgroups in Greek women with polycystic ovarian
      syndrome.
AB  - BACKGROUND: Since 2003, when the American Society for Reproductive Medicine
      (ASRM) and European Society of Human Reproduction and Embryology (ESHRE)
      sponsored consensus established criteria for polycystic ovarian syndrome (PCOS)
      diagnosis, the phenotypic spectrum of the syndrome has been significantly
      broadened. PURPOSE OF THE STUDY: This survey makes an effort to distinguish PCOS
      according to phenotypic expression and to estimate its prevalence in a Greek
      population. MATERIALS AND METHODS: Greek women from 18 to 35 years of age, who
      visited the outpatient department, claiming either irregular menstruation (oligo-
      or anovulation, OA) or clinical manifestations of hyperandrogenemia (HA) were
      recruited. They gave full disease history and underwent clinical examination,
      including transvaginal ultrasound (TVUS) scan to identify PCO morphology. Blood
      samples were collected to perform hormonal and metabolic analyses. Acute or
      chronic disorders were excluded. Finally, 266 PCOS women constituted the study
      population. CONCLUSIONS: The full-blown phenotype (HA+OA+PCO) is the predominant
      phenotype in this Greek population.

PMID- 23971254
TI  - Does Kruger's strict criteria have prognostic value in predicting ICSI clinical
      results?
AB  - OBJECTIVE: The purpose of this study was to compare clinical results of ICSI for
      different sperm morphology subgroups divided according to Kruger's classification
      system. MATERIALS AND METHODS: This retrospectively study was conducted at Zeynep
      Kamil Training and Researching Hospital in Istanbul (Turkey). The study included
      332 intracytoplasmic sperm injection (ICSI) cycles. The patients were under 37
      years of age with primary infertility who were admitted to the Department of
      Reproductive Endocrinology and Infertility, from January 2005 to June 2009. The
      patients were divided in three groups based on Kruger's strict criteria. Normal
      sperm morphology was less than 4% in group 1, between 4-14% in group 2, and
      greater than 14% in group 3. All patients underwent ICSI and embryo transfer (ET)
      following controlled ovarian hyperstimulation (COH). The groups were compared to
      the rates of fertilization, implantation, clinical pregnancy, abortion, and live
      birth. RESULTS: Pregnancy occurred in 132 (39.7%) of all ICSI cycles. There was
      no statistically significant difference between regarding groups regarding the
      rates of fertilization, implantation, clinical pregnancy, biochemical pregnancy,
      abortion, and live birth. CONCLUSION: The authors concluded that the normal sperm
      morphology defined by Kruger's strict criteria and sperm motility will not be
      able to predict prognosis of ICSI cycles.

PMID- 23971255
TI  - Maternal adiponectin and visfatin concentrations in normal and complicated
      pregnancies.
AB  - OBJECTIVE: To evaluate the role of adiponectin and visfatin in the
      pathophysiology of pre-eclampsia (PE) and how their concentrations correlate with
      the severity of the disease and neonatal outcomes. STUDY DESIGN: A prospective
      case-control study was carried out in 52 preeclamptic and 28 healthy pregnant
      women during the third trimester. The maternal plasma concentrations of
      adiponectin and visfatin were determined. Neonatal outcomes were also recorded.
      RESULTS: Mean maternal plasma adiponectin concentrations in healthy pregnant
      women did not differ significantly from those of mild PE and severe PE groups.
      The plasma adiponectin levels of PE patients with small for gestational age (SGA)
      and those without SGA did not differ significantly, but the median plasma
      visfatin concentration of patients with SGA fetus was significantly higher if the
      patient was preeclamptic (p = 0.036). CONCLUSION: The severity of preeclampsia
      did not change the plasma levels of adiponectin and visfatin, but the median
      plasma visfatin concentration of patients with SGA fetuses were significantly
      higher if the patient was preeclamptic. Altered levels of adipocytokines strongly
      imply that the regulation of adipocytokines in PE is different and more complex
      compared to that in healthy pregnancy.

PMID- 23971256
TI  - Platelet count as a predictive factor of neonatal outcome in twin pregnancy with
      fetal demise.
AB  - PURPOSE: During the last decade, the rate of twin pregnancies has increased and
      reached 3% of all pregnancies. MATERIALS AND METHODS: This study enrolled 36 twin
      pregnancies that were followed and delivered at the Clinic for Gynecology and
      Obstetrics, Clinical Center of Serbia over a five-year period. RESULTS: The first
      group included 15 patients with a monochorionic twin pregnancy, and the second
      group consisted of 21 patients with a dichorionic twin pregnancy. The platelet
      count was significantly lower in patients with APGAR scores of more than 8, with
      an average of 185,000/ml, and in patients with a score of less than 4, the
      average count was 221,000/ml. The perinatal mortality rate of the surviving twin
      was 33% in the monochorionic group and 0.4% in the dichorionic group. CONCLUSION:
      An increase in the maternal platelet count can be used as a predictor for a
      negative neonatal outcome of the surviving twin.

PMID- 23971257
TI  - Effects of flavonoids from semen cuscutae on the hippocampal-hypothalamic
      pituitary-ovarian sex hormone receptors in female rats exposed to psychological
      stress.
AB  - OBJECTIVE: To investigate the effects of flavonoids from semen cuscutae (FSCs) on
      the hippocampal-hypothalamic-pituitary-ovarian sex hormone receptors in female
      rats exposed to psychological stress and to explore the related mechanism.
      MATERIALS AND METHODS: Flavonoids were obtained from semen cuscutae using solvent
      extraction and polyamide column chromatography. Sound, light, and electricity
      were combined into psychological stress for endocrine dysfunction model
      establishment in female rats. The effects of FSCs on estrogen receptor (ER) in
      the hippocampus, hypothalamus, and pituitaries, as well as on follicle
      stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) in the
      ovaries of the psychologically stressed rats were quantitatively analyzed using
      immunohistochemistry and image analysis. RESULTS: FSCs increased ER expression in
      the hippocampus, hypothalamus, and pituitaries, as well as LHR expression in the
      ovaries, but had no effect on FSHR expression in the ovaries. CONCLUSION: FSCs
      are an effective medicine in the treatment of ovarian endocrine dysfunction in
      psychologically stressed rats.

PMID- 23971258
TI  - Clinical features and treatment of lactational mastitis: the experience from a
      binational study.
AB  - The characteristics of 38 patients with mastitis are listed in this study,
      including nationality, age, parity, history of mastitis, clinical and laboratory
      findings, and medical treatment. Differential diagnosis was mainly correlated to
      breast engorgement. Mastitis was primarily related to staphylococcus aureus and
      it was more common in primiparous patients.

PMID- 23971260
TI  - The use of sympathomimetic amines for the treatment of severe constipation
      refractory to conventional therapy--case report.
AB  - PURPOSE: Sympathetic nervous system hypofunction has been found to be associated
      with motility disorders of the bowel, including gastroparesis, pseudointestinal
      obstruction, and esophageal motility disorders. These disorders respond to
      sympathomimetic amine therapy. The purpose of this study was to see if this
      therapy could be effective in treating pathological constipation. MATERIALS AND
      METHODS: Dextroamphetamine sulfate 15 mg extended release capsules was prescribed
      to an 18-year-old young woman who had severe constipation with a bowel movement
      every two to three weeks and sometimes every five to six weeks who did not
      respond to standard therapy and where no definite etiology was determined.
      RESULTS: Two hours after her first dosage of the sympathomimetic amine, she had a
      bowel movement and has had regular bowel movements ever since. CONCLUSIONS:
      Sympathomimetic amine therapy seems to help severe constipation refractory to
      standard therapy.

PMID- 23971259
TI  - Perinatal outcome of singleton pregnancies following in vitro fertilization.
AB  - PURPOSE OF INVESTIGATION: To determine whether in vitro
      fertilization/intracytoplasmatic sperm injection (IVF/ICSI) singleton pregnancies
      are at increased risk for maternal and fetal complications than spontaneous
      singleton conceptions. MATERIALS AND METHODS: The pregnancy outcome of 634
      singleton pregnancies after IVF/ICSI delivered at the Clinic for Gynecology and
      Obstetrics during the period January 2006 to January 2010 were compared to 634
      matched singleton controls, matched one by one by age, parity, education, and
      body mass index (BMI). Differences in pregnancy outcomes between the groups were
      assessed using Student's t-test with Yates correction for continuous variables
      and Chi-squared test for categorical variables. RESULTS: The mean gestational age
      at delivery of the IVF group was 38.13 +/- 1.72 weeks, slightly shorter than
      spontaneously conceived singletons at 38.65 +/- 1.79 weeks. The diagnosis of
      gestational diabetes mellitus (GDM) was frequently made in the IVF group (11.82%
      vs 8.35%, t = 2.052, p < 0.05). Total preterm delivery rate of IVF pregnancies
      was 9.30%, significantly higher than the controls 5.85% (t = 2.33, p < 0.05),
      especially at the 30-32 weeks gestation period. The predominant mode of delivery
      after IVF pregnancy was cesarean section (80.75% vs 31.38% at spontaneously
      conceived, t = 17.71, p < 0.001), while vaginal route was the choice for
      naturally originated pregnancies 68.6% vs 19.24% (p < 0.01). No differences were
      found in the average birth weights, LBW, VLBW, SGA, and LGA regarding the
      pregnancy origin. Perinatal mortality rates were comparable among singletons with
      different pregnancy origin. CONCLUSIONS: Singletons from IVF/ICSI pregnancies
      have poorer perinatal outcome associated with higher rates of cesarean sections,
      preterm birth and prematurity, fetal malpresentation (breech presentation), and
      the occurrence of maternal GDM in pregnancy.

PMID- 23971261
TI  - Vanishing twins in diamniotic dichorionic in vitro fertilization gestation in mid
      second trimester.
AB  - The authors report a diamniotic dichorionic twin pregnancy after in vitro
      fertilization (IVF) in mid-second trimester. The dead fetuses were delivered by
      cesarean section at the 20th week of gestation. The authors discuss management
      aspects and review of the literature.

PMID- 23971262
TI  - Management of a late-presenting complex--an unclassified uterine anomaly in the
      presence of large leiomyomas.
AB  - This is a case report of a unique, late-presenting, Mullerian anomaly in an
      infertile patient. The authors discuss the diagnostic challenges of
      characterizing distorted gynecological anatomy by Mullerian anomalies in the
      presence of sizeable coexisting fibroids. This case report adds new insight to
      the already-existing understanding of Mullerian anomalies by demonstrating how a
      symptomatic and benign uterine pathology can complicate the diagnosis and
      management of patients with Mullerian defects.

PMID- 23971263
TI  - Herlyn-Werner-Wunderlich syndrome--a case report.
AB  - This is a case report of Herlyn-Werner-Wunderlich syndrome in a 28-year-old
      patient. She was admitted to hospital for surgical treatment of the pelvic mass
      accompanied by painful menstruation periods. This syndrome was diagnosed by US
      and MRI and it was treated by hemi-hysterectomy with vaginectomy. After the
      surgery, the patient has had regular and painless menstruation.

PMID- 23971264
TI  - Gonadotropinoma presenting as a case of pseudo-ovarian failure changing to
      macroprolactinoma.
AB  - PURPOSE: To present the first gonadotropinoma presenting as pseudo-menopause in a
      teenager. METHODS: Human menopausal gonadotropins (hMG) were given to a 37-year
      old woman whose hypergonadotropic amenorrhea with estrogen deficiency as a
      teenager was changed to hypogonadotropic amenorrhea by the growth and prolactin
      secretion of a macroprolactinoma. RESULTS: The patient responded multiple times,
      and every time to stimulation with hMG and each time produced several dominant
      follicles. She delivered two babies including conception at age 40. CONCLUSIONS:
      The fact that this woman could respond consistently to hMG 20 years after the
      diagnosis of premature menopause, it is clear that initially the etiology of the
      extremely high LH and FSH levels in an estrogen-deficient 18-year-old was the
      presence of gonadotropinoma secreting inert LH and FSH. Since serum prolactin was
      measured the first time at age 37, it is not clear whether the endogenous
      biologically active gonadotropine were suppressed by replacement of the
      gonadotroph cells with tumor cells or suppression of endogenous gonadotropins by
      hyperprolactinoma.

PMID- 23971265
TI  - Pregnancy with 15 live fetuses and severe ovarian hyperstimulation syndrome after
      ovulation induction and intrauterine insemination.
AB  - The empirical use of ovulation induction and intrauterine insemination for male
      factor infertility, unexplained infertility, and anovulatory infertility can be
      associated with multiple gestation and ovarian hyperstimulation syndrome (OHSS).
      A 30-year-old lady was referred for fetal reduction of very high-order pregnancy.
      She became pregnant after ovulation induction and artificial insemination. The
      stimulation protocol included clomiphene citrate and fixed-dose gonadotropins.
      Triggering of ovulation was done with 5,000 units of human chorionic
      gonadotropins (hCG). Cycle monitoring was done with ultrasonography only. The
      patient was admitted to the hospital due to severe OHSS. Physical examination
      revealed that the uterus size was equivalent to 28 weeks gestation. Transvaginal
      ultrasonography (TVUS) and pelvic magnetic resonance imaging (MRI) showed 15
      intrauterine gestational sacs with viable eight-week fetuses and 7 cm x 4.5 cm
      fluid collection. Both ovaries were enlarged. The right ovary was 12 cm x 5 cm
      and the left ovary was 10 cm x 6.5 cm. The patient had a spontaneous miscarriage
      of the 15 fetuses.

PMID- 23971266
TI  - The significance of 3D power Doppler in prenatal diagnosis and the evaluation of
      the anatomical structure of vein of Galen aneurysmatic malformation: case report.
AB  - Prenatal diagnosis of vein of Galen aneurysmatic malformation (VGAM) is made with
      the use of color Doppler, while in B-mode it is seen as a centrally placed
      supratentorial cystic structure. 3D-power Doppler (3D-PD) is a method that
      enables precise visualization of the vascular anatomy of this complex
      malformation. In our case, VGAM was detected in the 33rd week of gestation with
      power Doppler, and the use of 3D-PD enabled better visualization of the
      angioarchitecture and detection of feeding and drainage vessels of aneurysmatic
      widening. The diagnosis was confirmed postnatally with the use of MRI. A prenatal
      study of the angioarchitecture could have prognostic significance as well as
      being important in the therapeutic approach during the postnatal period.

PMID- 23971267
TI  - Cesarean section scar pregnancy treatment--case report.
AB  - This is a case report of a 36-year-old patient with an ectopic pregnancy located
      in the previous cesarean section scar following in vitro fertilization (IVF). The
      patient was treated by 50 mg of intrasacular methotrexate locally under
      ultrasound guidance. Transvaginal ultrasound (TVUS) confirmed that the pregnancy
      was no longer vital within 24 hours, dilatation and aspiration of the ovular
      tissue were performed after seven days and it was sent for pathohistological
      analysis. Eight hours after the procedure, the patient began bleeding abundantly
      and was consequently treated locally by 1 ml of Beriplast P Combi set, human
      fibrinogen, and human thrombin set (CSL Behring). After the treatment, the
      patient was discharged in good health, with normal laboratory values. Her
      menstrual period resumed 35 days after the procedure.

PMID- 23971268
TI  - Successful pregnancy after pulmonary embolism and heparin-induced
      thrombocytopenia--case report.
AB  - The authors present the case of a nulliparous 34-year-old patient. At the tenth
      week of gestation, she developed phlebothrombosis of veins of the right leg and
      massive pulmonary embolism. After thrombolytic and heparin therapy she developed
      rethrombosis and heparin-induced thrombocytopenia type II. Lepirudin was
      introduced in therapy and in the 12th week of gestation acenocumarol was added.
      After the 34th week, she received danaparoid sodium. After a week, by cesarean
      section, a healthy and mature female was delivered.

PMID- 23971269
TI  - Management of acute asthma in the pediatric patient: an evidence-based review.
AB  - Asthma is the most common chronic disease of childhood, with asthma exacerbations
      and wheezing resulting in more than 2 million emergency department visits per
      year. Symptoms can vary from mild shortness of breath to fatal status
      asthmaticus. Given the high prevalence of asthma and its potential to progress
      from mild to moderate to life-threatening, it is vital for emergency clinicians
      to have a thorough understanding of acute asthma management. Current evidence
      clearly supports the use of inhaled bronchodilators and systemic steroids as
      first-line agents. However, in those who fail to respond to nitial therapies, a
      variety of adjunct therapies and interventions are available with varying degrees
      of evidence to support their use. This review focuses specifically on evaluation
      and treatment of pediatric asthma in the emergency department and reviews the
      current evidence for various modes of treatment.

PMID- 23971270
TI  - An evidence-based approach to managing acute otitis media.
AB  - Acute otitis media is one of the most common pediatric illnesses; however, there
      is considerable controversy in its management. While most cases are treated with
      antibiotics, there is a growing concern regarding antibiotic overuse and
      subsequent drug resistance. Researchers in the Netherlands have developed a
      "watchful waiting" (ie, an observation approach) that has been successful in
      treating acute otitis media, although it has not gained widespread popularity in
      the United States. This review will summarize the latest research on diagnosing
      acute otitis media as well as different treatment regimens, including the
      efficacy of the watchful-waiting approach.

PMID- 23971271
TI  - Pediatric diabetic ketoacidosis: an outpatient perspective on evaluation and
      management.
AB  - Diabetic ketoacidosis is a common, serious acute complication in children with
      diabetes mellitus. Diabetic ketoacidosis can accompany new-onset type 1 diabetes
      mellitus or it can occur with established type 1 diabetes mellitus during the
      increased demands of an acute illness or with decreased insulin delivery due to
      omitted doses or insulin pump failure. Additionally, diabetic ketoacidosis
      episodes in children with type 2 diabetes mellitus are being reported with
      greater frequency. Although the diagnosis is usually straightforward in a known
      diabetes patient with expected findings, a fair proportion of patients with new
      onset diabetes present in diabetic ketoacidosis. The initial management of
      children with diabetic ketoacidosis frequently occurs in an emergency department.
      Physicians must be aware that diabetic ketoacidosis is an important consideration
      in the differential diagnosis of pediatric metabolic acidosis. This review will
      acquaint emergency medicine clinicians with the pathophysiology, treatment, and
      potential complications of this disorder.

PMID- 23971272
TI  - Evaluation of the febrile young infant: an update.
AB  - The febrile young infant is commonly encountered in the emergency department, and
      the incidence of serious bacterial infection in these patients is as high as 15%.
      Undiagnosed bacterial infections such as meningitis and bacteremia can lead to
      overwhelming sepsis and death or neurologic sequelae. Undetected urinary tract
      infection can lead to pyelonephritis and renal scarring. These outcomes
      necessitate the evaluation for a bacterial source of fever; therefore,
      performance of a full sepsis workup is recommended to rule out bacteremia,
      urinary tract infection, and bacterial meningitis in addition to other invasive
      bacterial diseases including pneumonia, bacterial enteritis, cellulitis, and
      osteomyelitis. Parents and emergency clinicians often question the necessity of
      this approach in the well-appearing febrile young infant, and it is important to
      understand and communicate the evidence that guides the approach to these
      patients. Recent studies examining the risk of serious bacterial infection in
      young infants with bronchiolitis and the role of viral testing in the febrile
      young infant will also be discussed in this review.

PMID- 23971273
TI  - The responsible dental radiographer.

PMID- 23971274
TI  - How to evaluate the efficacy of pit and fissure sealants.

PMID- 23971275
TI  - An expose of exposures, or rational radiography?

PMID- 23971276
TI  - Promoting dental health through water fluoridation.

PMID- 23971277
TI  - Responsible use of cone beam computed tomography: minimising medico-legal risks.
AB  - This communication highlights some of the ethical and possible legal
      responsibilities which pertain to the taking, reading, reporting, and
      communication of findings from cone-beam computed tomography (CBCT) scans. The
      importance of knowledge of head and neck anatomy and pathology to reduce the
      likelihood of incorrect interpretation is emphasised. Failure to detect critical
      findings in any diagnostic image can potentially result in medico-legal
      consequences. CBCT is no exception to this rule. Dental schools are advised to
      include CBCT imaging as a diagnostic tool in their under- and postgraduate
      curricula thereby equipping graduates to use 3D imaging in general and CBCT in
      particular. Existing dental practitioners are advised to seek continuing
      education on 3D imaging as part of their required lifelong learning.

PMID- 23971278
TI  - The relationship between periodontitis and diabetes: a brief review.
AB  - It has been reported that a close association exists between inflammatory
      periodontal diseases and diabetes through which one exerts a reciprocal influence
      on the other. This two-way relationship is based on the extensively reported
      assumption that the one condition so modifies the systemic and local environments
      that the progress of the other is favoured. On the other hand, treating and
      eliminating inflammatory periodontal diseases results in improved glycaemic
      control which minimises the microvascular complications of diabetes. This paper
      provides a brief review in an endeavour to create a better understanding of the
      interaction between these two relatively common conditions.

PMID- 23971279
TI  - Dentists and dental technician contractors.

PMID- 23971280
TI  - Maxillo-facial radiology case 112. Osteosarcoma.

PMID- 23971281
TI  - Oral medicine case book 51: actinic cheilitis in a patient with oculocutaneous
      albinism.
AB  - Patients with oculocutaneous albinism are more prone to sun-induced damage due to
      the lack of melanin. Actinic cheilitis is a potentially malignant disorder that
      occurs due to chronic UV-B radiation to the vermillion region of the lip, a
      region that is already at risk due to its morphology. A case of actinic cheilitis
      in a patient with oculocutaneous albinism is presented with a literature review.

PMID- 23971282
TI  - The perils of under-treatment--by not extracting asymptomatic third molar teeth,
      am I under-prescribing?

PMID- 23971283
TI  - Cast a bigger shadow.

PMID- 23971284
TI  - SADA communique. Competition Commission.

PMID- 23971285
TI  - Paedodontic general anaesthesia and compliance with follow-up visits at a
      tertiary oral and dental hospital, South Africa.
AB  - OBJECTIVES: The study aimed to describe the demographic profile of children
      receiving dental general anaesthesia (DGA) at the Pretoria Oral-and-Dental
      Hospital, South Africa, the type of treatment received and the level of
      compliance with the six-month preventive follow-up visit. METHODS: Retrospective
      review of records of children treated under DGA between January 2009 and December
      2010. RESULTS: The study group contained 78-children. Of these, 79.5% were
      between one and four years of age (mean 3.7-years; SD: 2.01), and 54% were
      female. The parents of more than half the sample (56.4%) were unemployed. The
      majority (55.2%) recorded no medical condition prior to undergoing DGA. Of the
      treatments performed, 63% were extractions (mean = 4.7 teeth/child), 51% involved
      placement of composite restorations (mean = 3.4 teeth) and 18% were fitting of
      stainless steel crowns (mean = 2.1 teeth). No preventive treatment was performed
      under DGA. Only 14 children (18%) returned within 15-months for follow-ups. Seven
      returnees were re-booked for a second DGA appointment for severely carious teeth;
      the rest received preventive treatment. Female children (Odds Ratio (OR): 0.28; p
      = 0.04) and children with no medical-condition (OR: 0.20; p = 0.03) were less
      likely to return for a follow-up visit. Children with employed parents were more
      likely (OR: 3.50; p = 0.09) to return for follow-ups. CONCLUSION: This study
      highlights the importance of preventive treatment prior to and during DGA,
      especially in a setting where the caries disease burden and unemployment are
      high.

PMID- 23971286
TI  - The relation between oral impacts on daily performances and perceived clinical
      oral conditions in primary school children in the Ugu District, Kwazulu Natal,
      South Africa.
AB  - Few studies have related the common oral health related quality of life (OHRQoL)
      impacts in children to perceived causes. OBJECTIVE: To assess the prevalence,
      extent and intensity of oral impacts in relation to perceived clinical conditions
      in primary school children in South Africa. METHODS: Cross-sectional study of a
      random sample of children attending 26 schools. The Child Oral Impacts on Daily
      Performance (Child-OIDP) index, administered through individual face-to-face
      interviews, was used. RESULTS: Sixty four per cent of the sample of 2610 children
      aged 11-13 years participated. 36.2% reported having one or more oral impacts on
      daily performances, 61.1% having one affected and 63.1% reporting impacts were of
      "very little" or "little" intensity. Eating was most commonly affected (22.8%)
      mainly related to decay (40%), followed by cleaning the teeth (17.2%). Toothache
      impacted on speaking (32.5%), whereas toothache (35.7%) and tooth decay (28.6%)
      influenced studying. Position of teeth impacted on smiling (19.2%), social (8.5%)
      and speaking (7.5%). Bleeding gums" and "tooth colour" affected cleaning teeth
      and smiling respectively. CONCLUSIONS: The prevalence of oral impacts on the
      quality of life in this South African population of schoolchildren was relatively
      modest, as was the extent and intensity of the impacts, affecting mainly eating,
      cleaning of teeth and smiling.

PMID- 23971287
TI  - Promoting a dental practice.

PMID- 23971288
TI  - Home gingivectomy.

PMID- 23971289
TI  - Maxillo-facial radiology case 111. Chondrosarcoma.

PMID- 23971290
TI  - Oral medicine case book 50: HIV associated Kaposi sarcoma.

PMID- 23971291
TI  - How do I comment ethically on the work of colleagues?
AB  - Patients are entitled to know about their dental and oral health, and
      practitioners have an ethical duty to inform them on an honest and factual basis.
      If this can be done without denigrating one's colleagues in any way, both
      patients and practitioners can benefit. As professionals, our first obligation is
      to place the well-being of our patients ahead of our own interests. First and
      foremost and for patient autonomy, we must give patients complete and truthful
      information regarding their current oral health status. When asked to comment on
      another dentist's treatment, it is not unethical or unprofessional to remember
      that the burden of proof regarding faulty or bad treatment s demanding and a
      prudent dentist must exercise great caution before making comments about other
      dentist's treatment. Uninformed and unjustifiable criticism is disparaging and
      can lead to unpleasant consequences for the unwary professional. Comprehensive
      and accurate records would be needed by both dentists to support their clinical
      judgement, if this case ever resulted in a complaint.

PMID- 23971292
TI  - Fee for all.

PMID- 23971293
TI  - SADA communique.

PMID- 23971294
TI  - Prescribed minimum benefits and how the concept applies to dentistry.

PMID- 23971295
TI  - Services rendered and barriers faced by public sector oral hygienists in two
      provinces of South Africa.
AB  - Oral hygienists (OHs) drive oral disease preventive programmes and promote good
      health practices. South Africa (SA) has a shortage of this cadre of health worker
      especially in the public sector. This 2009 project was the first effort to
      determine the professional activities performed, barriers faced and work- related
      issues that affected OHs employed at that time in Gauteng and in KwaZulu-Natal.
      The cross-sectional descriptive study used a self-administered questionnaire
      developed after a comprehensive literature review. The response rate was 78% (N =
      32). Almost all (94%) respondents gave "providing a service to the community" as
      the main reason for working in the public sector, where they were committed to
      offering preventative oral and dental services at clinics and in the community.
      Common employment problems were poor salaries (94%), lack of resources (81%) and
      the perception that opportunities for promotion are limited (78%), compounded by
      poor recognition of the services provided by OHs. In order to more effectively
      utilise the skills and commitment of OHs in delivering preventive dentistry in
      the public sector, such problems facing the profession should be addressed.

PMID- 23971296
TI  - The association between periodontitis and pre-term birth and/or low birth weight:
      a literature review.
AB  - Infections have been strongly associated with adverse pregnancy outcomes like pre
      term and/or low birth weight (PTLBW). There is substantial evidence on the direct
      association of genito-urinary infections and the incidence of PTLBW. Numerous
      cases of adverse pregnancy outcomes without maternal genito-urinary infection but
      nevertheless high levels of the tumour necrosis factor alpha (TNF-alpha) and
      prostaglandin E2 (PGE2) in the amniotic fluid, have been recorded. These findings
      alluded to the presence of infection elsewhere in the body. This paper reviews
      the literature on the association between the infective condition of
      periodontitis and PTLBW.

PMID- 23971297
TI  - Trends and ethnic disparities in oral and oro-pharyngeal cancers in South Africa,
      1992-2001.
AB  - OBJECTIVE: To describe trends in the epidemiology of oral and of oro-pharyngeal
      (OAP) cancers in South Africa for the atest period available. METHODS: Data were
      obtained from the South African pathology-based National Cancer Registry. All new
      cases of OAP cancers diagnosed and confirmed histologically from 1992 to 2001 are
      included for the ICD-10 sites C00 to C14, excluding those involving the major
      salivary glands (C07-C08) and the nasopharynx (C11). OAP cancer incidence is
      reported by demographics (gender, age, race/ethnicity) and the anatomical sites
      involved. The analysis on anatomical sites was restricted to squamous cell
      carcinomas. RESULTS: Overall, males had a much higher OAP cancer incidence rate
      (world age-Standardised incidence rate [ASIR] = 7.01/100 000 per year) than
      females (ASIR = 1.99). However, among Asian/Indian South Africans, OAP cancer
      incidence was higher among females (ASIR = 4.60) than among males (ASIR = 3.80).
      OAP cancer, excluding those involving the lip, was highest among Coloureds (ASIR
      = 5.72) and lowest among Blacks (ASIR = 3.16). OAP cancer incidence was stable
      overall, but incidence rates increased significantly among Coloured South
      Africans over the period under review (p < 0.05). Cancer specifically involving
      the oro-pharyngeal was most common among Coloureds and showed an increasing trend
      during the period under review. CONCLUSIONS: Variations in the incidence of OAP
      cancers by gender, race/ethnicity and anatomic site indicate a need for
      culturally-targeted reductions in major risk factors, including promoting tobacco
      cessation and prevention of risky alcohol use. The implications of the role of
      the human papillomavirus (HPV) in the prevention of squamous cell carcinomas
      involving the oro-pharyngeal in South Africa require further investigation.

PMID- 23971298
TI  - Alcohol and oral squamous cell carcinoma.
AB  - Alcohol is a risk factor for oral squamous cell carcinoma. It enhances the
      permeability of the oral epithelium, acts as a solvent for tobacco carcinogens,
      induces basal-cell proliferation, and generates free radicals and acetaldehyde,
      which have the capacity to cause DNA damage. Alcohol-associated malnutrition and
      immune suppression may further promote carcinogenesis. However, acetaldehyde, the
      first metabolite of ethanol, is the critical agent by which prolonged and
      excessive consumption of alcoholic beverages increases the risk of oral squamous
      cell carcinoma. Alcohol also acts synergistically with the products of tobacco
      combustion in the pathogenesis of oral squamous cell carcinoma.

PMID- 23971299
TI  - Maxillo-facial radiology case 110. Ameloblastic fibroma.

PMID- 23971300
TI  - Oral medicine case book 49: Plasmablastic lymphoma.

PMID- 23971301
TI  - Out-of-hours and emergency cover.

PMID- 23971302
TI  - The challenge of caring for adolescents and young adults.

PMID- 23971303
TI  - Debriefing: a valuable component of staff support.

PMID- 23971304
TI  - The 3rd International Public Health and Palliative Care Conference.

PMID- 23971305
TI  - Challenges and responses in providing palliative care for people living with
      HIV/AIDS.
AB  - HIV/AIDS has become a chronic and manageable disease owing to the remarkable
      advancement in medication, and it is now suggested that a palliative approach
      should be integrated into the trajectory of the disease to alleviate patients'
      psychosocial distress and optimally improve their quality of life.This article
      synthesises a body of literature to highlight several clinical and systematic
      challenges that should be addressed in implementing a palliative approach to care
      for HIV/AIDS patients. They involve pain and symptom management, health-care
      providers' perceptions of HIV/AIDS, patients' beliefs about palliative care,
      variability in informal care resources, socioeconomic and demographic
      determinants of palliative care, and difficulties in evaluating the effectiveness
      of palliative care. To inform current practice in the palliative care domain,
      responses to the identified challenges are discussed. A disease stage-specific
      model is also presented to respond to the prolonged course of HIV/AIDS.

PMID- 23971306
TI  - Advance care planning for people with dementia: benefits and challenges.
AB  - Advance care planning (ACP) is a process being championed within health and
      social care, particularly since the publication of the UK Department of Health's
      2008 End of Life Care Strategy. However, its implementation in dementia care is
      yet to be fully realised and can pose significant ethical and legal dilemmas for
      the generic and specialist workforce, the patient themselves, and their family or
      loved ones. Challenges may be attributable to inadequate communication, capacity
      issues, missed opportunities, and the perception that dementia is not a life
      limiting illness. The aim of this paper is to highlight the benefits of ACP for
      individuals with dementia while appraising the recognised barriers to assist in
      developing some realistic recommendations for future practice.

PMID- 23971307
TI  - Death in nursing homes: a Danish qualitative study.
AB  - Little is known about the quality of end-of-life care in Danish nursing homes
      (NHs). This qualitative descriptive study based on semi-structured group
      interviews with nursing staff members in three NHs in Copenhagen, Denmark, aimed
      to describe the participants' perceptions of end-of-life care in Danish NHs, with
      particular focus on medication administration and collaboration with GPs. Four
      main categories of problematic issues emerged: medication (problems with 'as
      needed' medication and lack of knowledge of subcutaneous administration),
      interpersonal relations (difficulties in cooperation and communication between
      relatives and GPs), decision making (problems concerning termination of life
      prolonging treatment and the need for early planning of end-of-life care), and
      professional development (documentation and education). Considerable improvements
      may be achieved primarily by educating and training nursing staff and GPs. More
      research is warranted to optimise end-of-life care in Danish NHs.

PMID- 23971308
TI  - The development of a falls prevention and management toolkit for hospices.
AB  - In 2008 a small group of people in the UK were brought together at the invitation
      of the charity Help the Hospices and with the support of the National Patient
      Safety Agency to create a falls prevention and management toolkit. The purpose of
      the toolkit was to assist hospices to manage and if possible prevent falls in
      their in-patient units and day care centres.This Falls Prevention Working Group
      put together a policy, care plan, and incident report form designed to enable an
      accurate and effective assessment of patients' needs and minimise harm while
      supporting patient independence. A draft version of the toolkit was trialled by
      nine hospices in 2009. Following revision, a final version was published on the
      Help the Hospices and Patient Safety First websites in 2010 and introduced with
      workshops in two separate locations in the UK. This paper provides an overview of
      the development process and presents evidence, albeit limited, that in-patient
      falls in hospices are reducing. The toolkit provides outcome measures of better
      patient care in falls management and prevention.

PMID- 23971309
TI  - Missed opportunities: a case study of barriers to the delivery of palliative care
      on neonatal intensive care units.
AB  - Despite clear guidance from the Royal College of Paediatrics and Child Heath and
      Together for Short Lives, among others, the delivery of palliative care remains
      inconsistent on neonatal intensive care units, with many infants receiving full
      intensive care measures until the final moments of their lives. This case study
      identifies barriers faced by members of the neonatal team: fear of respiratory
      depression surrounding opiate use at the end of life, conflict among members of
      the care team leading to moral distress, and inadequate training and support for
      staff, which can inhibit the full transition to a palliative care framework at
      the end of life. Recommendations from the literature are collated to address
      these barriers.Training programmes for staff covering the tenets of palliative
      care, including symptom management, analgesic use, and communication skills, as
      well as regular multidisciplinary forums and debriefings are necessary to improve
      the care provided to infants and their families where there is a palliative care
      need.

PMID- 23971310
TI  - Nurses must never be talked out of their role.

PMID- 23971311
TI  - Call for standard HCA certificate.

PMID- 23971312
TI  - Schwartz rounds provide a dedicated time for reflection.

PMID- 23971313
TI  - Has nobody told Mr Hunt about the GP system in this country?

PMID- 23971314
TI  - Caring for staff will allow them to provide good care.

PMID- 23971315
TI  - Causes and treatment of malignant melanoma.
AB  - The incidence of melanoma is rising faster than any other malignancy. As more
      cases are diagnosed, it is likely that general nurses will come into contact with
      melanoma patients. This article discusses the identification, treatment and
      prognosis for this group of patients.

PMID- 23971316
TI  - Perioperative glucose control for patients with diabetes.

PMID- 23971317
TI  - Identifying signs of retinoblastoma.

PMID- 23971318
TI  - The assessment and management of psoriasis.
AB  - Psoriasis is a long-term, inflammatory skin condition that affects around 1.3
      2.2% of the UK population. Nurses involved in the assessment and treatment of
      people with psoriasis should take into account not only the condition's physical
      effects but also the increased risk of health problems linked to it and its
      psychological effects. This article highlights National Institute for Health and
      Clinical Excellence guidance, primarily for non-specialist practitioners.

PMID- 23971320
TI  - 60 seconds with Angela Wallace.

PMID- 23971319
TI  - Involving people with dementia in research.
AB  - This article considers some of the ethical issues in conducting research
      involving people with dementia. The process of gaining consent is explored, along
      with the issue of accidental disclosure of diagnosis. The importance of including
      people with dementia in research and the possible benefits to them of taking part
      are discussed and the issues are linked to practice through examples of my own
      research with people with dementia.

PMID- 23971321
TI  - The transition to adult care.

PMID- 23971322
TI  - The ability to recognise care is your most valuable asset.

PMID- 23971323
TI  - [Sports medicine: turns a page in Geneva].

PMID- 23971324
TI  - [Cardiovascular prevention in the sportsman: a role for statins?].
AB  - Official guidelines bring regularly the physician to consider a statin treatment
      in physically active individuals, including athletes. Several factors speak
      against such an attitude: the available risk scores are far from precise and do
      not sufficiently take into account lifestyle; when you correct for the level of
      physical activity, cholesterol loses its' predictive value; physical activity
      diminishing cardiovascular risk by at least a factor 2, an athlete is always at
      low risk. In addition, the secondary effects of statins are liable to interfere
      significantly with sport activities, paradoxically increasing the risk. Statin
      prescription should not be envisaged in athletes.

PMID- 23971325
TI  - [Anterior cruciate ligament injuries in children].
AB  - An increasing number of anterior cruciate ligament injuries are now seen in
      children and girls seem to be equally affected. Such neglected or untreated
      lesions could be the cause of early degenerative changes. Recently, many authors
      support the trend toward early surgical management in skeletally immature
      patients with complex meniscal tear or recurrent knee instability after proper
      rehabilitation. Improvement in pediatric knowledge and surgical techniques tend
      to support a tendency for more surgical treatment in children. The type of
      management is choosing according to history and physical examination. Magnetic
      resonance imaging is a useful tool not only for diagnosis but also for surgical
      treatment planning. We usually recommend anterior cruciate ligament
      reconstruction in children with knee instability or with further damages to the
      joint.

PMID- 23971326
TI  - [Sports and athletes deserve doping hunting].
AB  - This article reviews the evidence-based ergogenic potential adverse effects of
      the most common products in use by recreational and elite athletes today. This is
      an aggressively marketed and controversial area of sports medicine wordwide. It
      is therefore important for the scientific societies, clinicians, dieticians
      sports federations to be well versed in the more popular supplements and drugs in
      order to have an important role in information and prevention attitudes that can
      lead to health risks or addictions!

PMID- 23971327
TI  - [Influence of sport on isoinertial trunk muscle performance development: a 2
      years prospective study].
AB  - In this study, we investigate the relationship between either regular sports
      practice or a non sportive way of life, development of trunk muscle performance
      and occurrence of lower back pain between male schoolchildren. 93 schoolchildren
      were recruited, then stratified in 4 groups, according to sport practice or
      sedentary way of life. Participants were evaluated twice at an interval of 2
      years with an interview, a physical examination and an evaluation of trunk muscle
      performance. We identified that basketball players have significantly better
      results and perfomance concerning isometric and isoinertial tests of trunk
      muscles than the other groups. Differences in trunk muscle performance exist
      following the practice of different types of sport. We can deduce that trunk
      muscle performance has some sport specificity.

PMID- 23971328
TI  - [Return to sport after anterior cruciate ligament reconstruction].
AB  - Despite continuous advances in techniques for anterior cruciate ligament
      reconstruction (ACLR), return to play (RTP) after surgery remains a challenge.
      More than one-third of the patients are unable to return to their preinjury sport
      level, for most because of a fear to sustain another injury. And when a RTP is
      attempted, up to 20% will tear their graft and a similar % will sustain an ACL
      tear on the opposite side. We believe that these failures result from an
      incomplete recovery. Based on a literature review and on our experience, we
      suggest 6 objective criteria to allow a safer RTP. They rely on laxity, strength,
      neuromuscular function, and psychological evaluations. Rehabilitation after ACLR
      should focus on the deficits identified by these tests and on they specific needs
      of the sport that the athlete plans to return to.

PMID- 23971329
TI  - [Implementation of the ordinance on the protection of motherhood in female
      physicians].

PMID- 23971330
TI  - [Orphan diseases: what are the roles for associations? ].

PMID- 23971331
TI  - [Female genital mutilation: recommendations for practice].

PMID- 23971332
TI  - [Vaccination against papillomavirus: words of adolescents].

PMID- 23971333
TI  - [About the 2012 consensus on the diagnosis and treatment of patients with
      dementia].

PMID- 23971334
TI  - [Authors' reply].

PMID- 23971335
TI  - [Assisted suicide: will Switzerland enlighten France?].

PMID- 23971336
TI  - [Arrival of the refrigerator: a revolution in society].

PMID- 23971337
TI  - [Shadows and lights of HPV vaccination].

PMID- 23971338
TI  - [Yesterday, Viagra was a drug (2) ].

PMID- 23971339
TI  - [Questions without answer].

PMID- 23971340
TI  - Aspiring to excellence.

PMID- 23971341
TI  - Top tips for child protection for the GDP.
AB  - Knowledge of child protection is essential in everyday practice for the whole
      dental team as they are well placed to take part in the shared responsibility of
      protecting children. Physical abuse, neglect, sexual abuse and emotional abuse
      may all present to the dental team in various ways. This article aims to provide
      some top tips for general dental practitioners who have concerns regarding
      possible child abuse/neglect and remind them of what observations to make and
      what questions to ask themselves when they are concerned about a child's welfare.
      CLINICAL RELEVANCE: Abuse and neglect are areas in child protection that the
      dental team can provide important information about to the local child protection
      team. All members of the dental team need to be aware of the signs and symptoms
      of child abuse/neglect and where to go for help.

PMID- 23971342
TI  - Interceptive orthodontics--current evidence-based best practice.
AB  - This article examines the key areas relating to interceptive orthodontics, ie
      crossbites, anterior and posterior; eruption problems and impaction (including
      incisors and canines); poor quality first permanent molars; infra-occluded
      primary molar teeth; non-nutritive sucking habits (digit and pacifier sucking)
      leading to anterior openbite, posterior crossbite and increased overjet;
      centreline shifts related to unilateral loss of primary teeth; and increased
      overjet and associated risk of trauma. It aims to provide information and
      recommendations. CLINICAL RELEVANCE: The GDP requires evidence to support the
      clinical management of common problems presenting in the mixed dentition.

PMID- 23971343
TI  - Special care dentistry for general dental practice.
AB  - Although special care dentistry (SCD) is a fairly recent specialty, the
      principles and practice of SCD have been developed since the 1980s. Shared care
      of these patients with general dental practitioners remains vital to ensure that
      comprehensive care is provided. This article aims to discuss some of the patient
      groups commonly seen in SCD clinics and give an insight into the varied complex
      medical and social aspects of care which are managed as part of providing
      appropriate, safe and holistic care. CLINICAL RELEVANCE: Many patients who
      currently fall under the remit of special care dentistry could be treated safely
      in general dental practice. This article acts as an introduction to special care
      dentistry for general dental practitioners.

PMID- 23971344
TI  - Early detection of oral cancer: how do I ensure I don't miss a tumour?
AB  - The GDC recommend that early detection of oral cancer should form part of every
      dental surgeon's Continuing Professional Development. It is arguably the most
      serious condition that can arise within the oral cavity and regular screening
      practices may also help mitigate spurious claims of prior negligence for failure
      to detect the cancer at an early stage. Results for routine screening of the
      entire oral mucosa, together with risk status assessment, should be recorded in a
      patient's notes at every visit (both negative and positive findings). CLINICAL
      RELEVANCE: A knowledge of how to detect oral cancer early is an essential part of
      the dentist's armamentarium.

PMID- 23971345
TI  - The indicator of sedation need (IOSN).
AB  - Conscious sedation in dentistry is usually indicated because a patient's anxiety
      can prohibit the necessary dental treatment being undertaken. It may also be
      indicated because of unpleasant or lengthy treatment or to prevent exacerbation
      of a patient's medical or behavioural condition by anxiety. The indicator of
      sedation need (IOSN) tool has been developed to help support dentists in their
      clinical decision-making and uses information about a patient's anxiety, medical
      and behavioural status and treatment complexity. The IOSN has been used to
      measure sedation need and has shown that 5.1% of patients attending general
      dental practices have a high need of conscious sedation. IOSN has also been used
      to investigate the need for conscious sedation in the general population among
      dental practice attenders and those who don't attend. The proportion was found to
      be 6.7%. CLINICAL RELEVANCE: Some patients require conscious sedation in order to
      access dental care. The indicator of sedation need (IOSN) tool helps in the
      decision-making process.

PMID- 23971346
TI  - Treatment of peri-implant diseases: a review of the literature and protocol
      proposal.
AB  - Over 100,000 implants were placed in the UK in 2010. As the numbers of patients
      with implant-retained prostheses increases, operators are encountering an
      increasing number of biological implant complications, most commonly peri-implant
      mucositis and peri-implantitis. The effective management of these complications
      is crucial to maintain patients' oral health. In particular, in contrast to
      common periodontal infections, some peri-implant infections may benefit from
      surgical intervention as a first line approach. CLINICAL RELEVANCE: This article
      reviews the literature on the treatment options for peri-implant mucositis and
      peri-implantitis and proposes a protocol for their treatment.

PMID- 23971347
TI  - Accessing the best available evidence.
AB  - This narrative review aims to highlight sources of the best available evidence
      and describe primary clinical trials currently taking place in primary dental
      care across the United Kingdom which will add to the evidence base. CLINICAL
      RELEVANCE: To provide evidence-based dental care, dental professionals have to
      integrate the best available evidence, their clinical experience and their
      patients' values; this paper should help to identify user-friendly sources of the
      best available evidence.

PMID- 23971348
TI  - Reducing white spot lesion incidence during fixed appliance therapy.
AB  - Fixed orthodontic appliances are commonly used in contemporary orthodontic
      treatment and can be associated with the development of white spot lesions on the
      teeth. These lesions can be detrimental to both the aesthetics and health of the
      teeth so prevention is better than cure and patient selection is critical. This
      paper discusses predictors of development in addition to methods to help prevent
      white spot lesions during fixed appliance therapy. Recommendations for oral
      hygiene regimes during fixed orthodontic appliance treatment are given, the
      development of white spot lesions (WSLs) described and ways to predict their
      occurrence identified. CLINICAL RELEVANCE: Most general dental practitioners will
      have patients who are considering orthodontic treatment or are wearing fixed
      orthodontic appliances and so are at increased risk of developing WSLs. It is
      therefore important they are aware of predictors and ways to prevent WSLs.

PMID- 23971349
TI  - Oral medicine. 9: Orofacial pain.

PMID- 23971350
TI  - Technique tips--incisal tips.

PMID- 23971351
TI  - Physical signs for the general dental practitioner. Case 105. Horner's syndrome.

PMID- 23971352
TI  - [Orthorexia nervosa and it's background factors].
AB  - The place of orthorexia nervosa (ON)--described by Bratman in 1997--is not
      clearly defined in the diagnostic systems. However, the increasing number of
      clinical experiences and research data gives us more and more information about
      the epidemiology, and the social and individual characteristics of ON. The
      general population shows a 6.9% prevalence of ON; healthcare professionals are at
      high risk of ON with the prevalence rate of 35-57.6%. Education, the choice of
      profession, socioeconomic status and the internalization of the ideals of society
      are significant factors in the development of ON, while sex, age and body mass
      index do not seem to be determining variables in this respect. The lack of common
      criteria and proper research results on ON makes it impossible to generalize data
      on the general population. Further studies with larger representative samples and
      assessment instruments with good psychometric properties are necessary to make
      research data on ON comparable.

PMID- 23971353
TI  - [Prenatal diagnosis of central nervous system malformations].
AB  - The prenatal diagnosis of fetal malformations have been the subject of numerous
      publications in the literature. This has dramatically increased in the last 15
      years, mainly due to the advent of high-resolution ultrasound. In addition
      adequate guidelines issued by professional organizations have encouraged the
      universal approach to the imaging of fetal anatomy as well as malformations. One
      of the most significant groups of the fetal anomalies is the central nervous
      system malformation. Due to its prevalence and severity the praenatal diagnostics
      of central nervous system malformations got basic significance. In this review we
      attempted to summarize the recent informations concerning the prenatal
      diagnostics of the central nervous system anomalies.

PMID- 23971354
TI  - [Sacral insufficiency fractures].
AB  - BACKGROUND: The spontaneous osteoporotic fracture of the sacrum, known as a
      sacral insufficiency fracture (SIF) was first described as an unrecognized
      syndrome of the elderly by Laurie, in 1982. Numerous case histories and a few
      series of cases have been discussed in medical journals; however, none have been
      reported in Hungary. GOAL: To delineate the leading diagnostic steps in the
      recognition of SIF and review the therapeutic guidelines. CASE HISTORIES,
      METHODS: Between January 2009 and the first six months of 2010 11 cases of SIF
      were diagnosed at the National Center for Spinal Disorders. We examined the
      clinical aspects of the illness, the radiological modalities, the fracture
      markings, the pace of recovery and duration. RESULTS: The 11 patients were found
      to have various SIF predestining etiological factors and the following classic
      fractures--H-type, unilateral, horizontal, unilateral-horizontal and vertical as
      well as a bilateral pattern. In cases often not showing obvious clinical symptoms
      and in cases resulting in conventional radiological examinations of low
      sensitivity and specificity, we used mapping techniques in setting up the exact
      diagnosis. CONCLUSION: If we consider SIF from patient history and known risk
      factors, diagnostic procedure (primer original) may be shortened and a number of
      unnecessary tests (biopsy) may be avoided.

PMID- 23971355
TI  - [Exploration of the goals for the quality of life in primary rehabilitation after
      spinal cord injury].
AB  - BACKGROUND AND PURPOSE: Surveyed references indicate improvement of
      rehabilitation outcomes if based on exploration of personal rehabilitation goals
      or quality of life goals. Purpose of our study is mapping of quality of life
      goals of persons entering rehabilitation by structured interviews, and study of
      applicability of the method. METHODS: Structured interviews have been performed
      with persons consecutively admitted for their first rehabilitation intervention,
      meeting inclusion criteria. World Health Organization's quality of life measure
      brief version and disability module served as guideline for the interviews. For
      study any negative effect on rehabilitation of our approach we have compared
      rehabilitation outcomes of consecutively admitted persons immediately before
      starting our study (58) and those with closed rehabilitation intervention (53).
      For this purpose the Functional Independence Measure was used. Finally content
      analysis of the interviews has been performed. RESULTS: In 24 cases complications
      and psychological instability have prevented the inclusion, seven persons did not
      agree into participation in the study. Of the 71 interview participants the
      rehabilitation of 53 persons concluded. Their rehabilitation outcomes are better
      as of the control group significant difference has been measured in the social
      functions domain. Quality of life of included persons decreased during the
      rehabilitation process insignificantly, the autonomy domain showed insignificant
      improvement, the inclusion domain did not change. Content analysis revealed the
      outstanding role of the family among quality of life goals. CONCLUSIONS: Reported
      results indicate that exploration of quality of life goals of persons in early
      phase of rehabilitation after spinal cord injury is feasible. The selected
      quality of life measure may well support the interviews.

PMID- 23971356
TI  - [Survey of adults living with epilepsy in Hungary: health-related quality of life
      and costs].
AB  - BACKGROUND AND PURPOSE: Disease burden of epilepsy in Hungary is underexplored.
      The aim of our study was to assess the quality of life and costs of adults with
      epilepsy. METHODS: Cross-sectional questionnaire survey was performed in two
      hospital based outpatient neurology centres involving consecutive patients with
      epilepsy. Demography, clinical characteristics, health status (EQ-5D) and health
      care utilisation in the past 12 months were surveyed. Cost calculation was
      performed from the societal perspective. RESULTS: Altogether 100 patients (women
      58%) were involved, their mean age was 37.6 (SD = 12.5) years. Disease duration
      was 15.0 (SD = 12.1) years on average and 22 (22%) patients were disability
      pensioners. The EQ-5D score was mean 0.83 (SD = 0.24) which is significantly
      lower than the age-matched population norm (p = 0.017). Pain/discomfort and
      anxiety/depression are the most problematic health dimensions. The annual cost
      per patient was mean 2421 (SD = 3249) Euros (679 397 SD = 911 783 HUF;
      conversion: 1 Euro = 280.6 HUF), distribution between direct medical, direct non
      medical and indirect costs was 33%, 18% or 49%. Patients with seizure in the past
      12 months have higher cost on avergare than the asymptomatic subsample (3119 vs.
      988 Euros/patient/year; 935 481 vs. 277 209 HUF/patient/year). CONCLUSION: Adults
      with epilepsy have significantly worse health status by the EQ-5D than the gender
      and age matched Hungarian general population. Disease related costs are
      significant especially in cases with seizure, productivity loss related costs are
      dominant. Our study provides basic data for clinical and sustainable health care
      financing decisions.

PMID- 23971357
TI  - [Survey of adults living with epilepsy in Hungary: health-related quality of life
      and costs].

PMID- 23971358
TI  - Transcranial Doppler assessment of cerebral vasomotor reactivity in evaluating
      the effects of vinpocetine in cerebral small vessel disease: a pilot study.
AB  - BACKGROUND: There are still dilemmas about the vasodilating effect of
      vinpocetine, a synthetic ethyl alkaloid vincamine. The method of measuring
      cerebral vasomotor reactivity (VMR) by transcranial Doppler (TCD) technique
      before and after administration of the medication was used to estimate the degree
      of arterioles vasodilatation. The aim of this study was to test of the
      vasodilating effect of vinpocetine in patients with cerebral small vessel disease
      (SVD) by measuring cerebral VMR. MATERIAL AND METHODS: Thirty patients with SVD
      were on 3-month-long oral treatment with 15 mg vinpocetine daily. Cerebral VMR
      was determined by breath holding test. The breath holding index (BHI) was
      calculated in standard manner and values > 0.69 were considered normal. At the
      baseline, before treatment (I), BHI, modified Rankin scale (mRS) score, Mini
      Mental State Examination (MMSE) score were determined. One month later (II) BHI
      was assessed again, while after 3 months of treatment (III) we analyzed BHI, mRS
      score and MMSE score. RESULTS: The average age of patients was 61.4 +/- 11.5
      years (range 40 to 77 years), 18 (60%) female and 12 (40%) males. Values of BHIs
      were increased during treatment at the right MCA (I) 1.18 +/- 0.53, (II) 1.26 +/-
      0.54, (III) 1.37 +/- 0.41, with statistical significance between I and III
      measurement (p < 0.05). An increase was noted on the left MCA (I) 1.25 +/- 0.53,
      (II) 1.31 +/- 0.55 and (III) 1.32 +/- 0.42, but it did not reach statistical
      significance (p > 0.05). Mean MMSE score significantly increased from baseline
      27.4 +/- 2.3 to 28.5 +/- 2.0 after three months of treatment (p < 0.001).
      Functional status showed a statistically significant improvement with mRS score
      increasing from 2.1 +/- 1.0 to 1.1 +/- 0.6 (p < 0.001). CONCLUSION: This pilot
      study showed that 3-month-long oral treatment with vinpocetine 15 mg daily had
      tendency to increase BHI, indicating improvement of cerebral VMR. It is possible
      that higher doses of vinpocetine are needed to achieve substantial increase of
      VMR.

PMID- 23971359
TI  - [Minor physical anomalies in autism].
AB  - BACKGROUND AND PURPOSE: Minor physical anomalies are mild, clinically and
      cosmetically insignificant errors of morphogenesis which have a prenatal origin
      and may bear major informational value for diagnostic, prognostic and
      epidemiological purposes. Since both the central nervous system and the skin are
      derived from the same ectodermal tissue in utero, minor physical anomalies can be
      external markers of abnormal brain development and they appear more commonly in
      neurodevelopmental disorders. In a recently published meta-analysis Ozgen et al.
      have published the results of seven studies--all have used the Waldrop Scale
      which contains 18 minor physical anomalies--and reported on the higher prevalence
      of minor physical anomalies among patients with autism. There are only a very few
      data on the individual analysis of the prevalence of minor physical anomalies in
      autism. METHODS: In our study we have studied the prevalence of 57 minor physical
      anomalies in 20 patients with autism and in 20 matched control subjects by the
      use of the Mehes Scale. RESULTS: The prevalence of minor physical anomalies was
      significantly higher in the autism group (p < 0.001). The individual analysis of
      the 57 minor physical anomalies showed the significantly more frequent apperance
      of four signs (primitive shape of ear p = 0.047, abnormal philtrum p = 0.001,
      clinodactylia p = 0.002, wide distance between toes 1 and 2 p = 0.003). No
      correlation was found between the four significantly more common minor physical
      anomalies. CONCLUSION: The higher prevalence of minor physical anomalies in
      autism supports the neurodevelopmental hypothesis of the disorder and the
      individual analysis of minor physical anomalies can help to understand the nature
      of the neurodevelopmental defect.

PMID- 23971360
TI  - [Nebivolol in treatment of multiple cerebral aneurysms].
AB  - INTRODUCTION: We examined the effect of nebivolol on blood pressure control after
      subarachnoidal hemorrhage in three patients with multiple aneurysms. PATIENTS AND
      METHODS: Endovascular intervention was applied to treat the bleeding aneurysms of
      all patients, and the silent aneurysms were followed-up. In all patients
      nebivolol was used as long-term anti-hypertensive medication. RESULTS: With
      nebivolol treatment the blood pressure in our patients was maintained in the
      normal range with no unexpected shoot-ups. The size of the silent aneurysms did
      not increase and the endovascularly treated aneurysms demonstrated acceptable
      morphology on follow-up catheter-angiography. DISCUSSION: After endovascular
      treatment of the bleeding aneurysm, strict blood pressure control is essential in
      those with multiple aneurysms to prevent the rupture of silent aneurysms.
      Antihypertensive medications with a 24-hour effect are preferable. Nebivolol
      seemed to be an appropriate medication for this purpose in all of our patients.

PMID- 23971361
TI  - Shunt insufficiency due to knot formation in the peritoneal catheter.
AB  - The authors report a rare case of the peripheral obstruction of a
      ventriculoperitoneal shunt. Premature baby was operated on hydrocephalus due to
      germinal matrix bleeding. After two months of implantation of venticuloperitoneal
      shunt peripheral insufficiency of the system was emerged. During the shunt
      revision extensive knot formation became visible. We simply cut the catheter
      above the knot and the working shunt was replaced into the abdominal cavity. The
      postoperative course was uneventful and the baby was free of complaints for more
      than one year. The pathomechanism of knot formation is not clear thus the
      discovery of the problem during the operation is an unexpected event. In our
      opinion tight knot cannot be spontaneously formed intraabdominally. Loose knots
      can be developed and can reduce the capacity of liquor flow. We think that the
      knot tightens during pulling out. Longer peritoneal catheters can precipitate
      multiple looping and/or axial torquations and increase the peripheral resistance
      of the shunt. In such cases when the pulling out is challenged conversion to
      laparotomy is suggested.

PMID- 23971362
TI  - [Effectiveness and safety of tolperisone in spasticity following cerebral stroke:
      randomized, double-blind, placebo-controlled trial].

PMID- 23971363
TI  - [Identification of new biomarkers, with special regard for the toxicity of free
      iron deposits in the nervous system, iron toxicity-induced oxidative stress and
      innate immune reactions (translational investigations)].

PMID- 23971364
TI  - [Neurorehabilitation, neurology, rehabilitation medicine].

PMID- 23971365
TI  - [The history and the present conditions of the occupational bladder cancer in our
      country].
AB  - PURPOSE: We examined the history and the present conditions of the occupational
      bladder cancer of our country and a chemical carcinogenesis study career of the
      bladder cancer. OBJECT AND METHOD: We performed consideration from literatures
      mainly on document and Ministry of Health, Labor and Welfare, Labor Standards
      Bureau, Accident compensation element document and documents of Association of
      Formation Product Industry. RESULT: Production of aromatic amine was started in
      about 1920 in our country, and the first occupational bladder cancer case was
      reported in 1940. It arrived at the greatest amount of production time of
      aromatic amine caused by Communist China Trade in 1955. The production, the
      import of benzidine and 2-naphthylamine were prohibited in 1972 by Safe Hygiene
      Method Official Announcement. During this time, 3,310 people were exposed by
      these materials, and the occupational bladder cancer of 357 people was registered
      by 1985. A number authorized from 1976 through 2006 that Workmen's comp was
      started is 341 cases of urinary tract system tumors by duties exposed to
      benzidine, 150 cases of urinary tract system tumors by duties exposed to 2
      naphthylamine and one case of urinary tract tumors by o-dianisidine in total 492
      cases. The occupational urinary tract cancer patient almost reaches a retirement
      age, and it is thought that they reach the end in about 2025. CONCLUSION: We
      reported the history and the present conditions of the occupational bladder
      cancer which occurred from 3,310 people of aromatic amine revelation in our
      country and we commented on a trend of the recent occupational bladder cancer for
      consideration from literatures.

PMID- 23971366
TI  - [A questionnaire survey of antimicrobial prophylaxis to prevent perioperative
      infection in urological field in Japan].
AB  - PURPOSE: To survey the present condition of administration method of the
      antimicrobial prophylactic (AMP) agents for the perioperative infection in Japan
      on revising "The Japanese guidelines for prevention of perioperative infections
      in urologic field (2006)". PATIENTS AND METHODS: With the approval of the
      Japanese Urological Association (JUA) in 2011, all of the principal urological
      training institutions certified by JUA (n = 836) were encouraged to participate
      to survey their adherence to the JUA guidelines (published in 2006) for AMP to
      prevent perioperative infection in urological field, and 446 (53.3%) institutions
      responded to the questionnaire. RESULTS: The rates of following the JUA
      guidelines of, "completely", "mainly", "not too much", and "not at all" were
      6.5%, 69.7%, 22.0% and 1.6%, respectively. The guidelines were followed for open
      clean operations in 48.5%, open clean-contaminated operations in 66.4%, open
      contaminated operations in 61.8%, laparoscopic clean operations in 54.1%,
      laparoscopic clean-contaminated operations in 61.2%, transurethral resection of
      bladder tumor in 71.5%, transurethral resection of prostate in 68.9%,
      ureteroscopy and transurethral ureterolithotomy in 68.2%, prostate biopsy in
      43.2%, and cystoscopy were in 42.2%, respectively. However, in terms of duration
      of AMP administration, the longer duration than those recommended by the
      guidelines were observed for clean surgery, transurethral resection of bladder
      tumor, ureteroscopy and transurethral ureterolithotomy, prostate biopsy, and
      cystoscopy. CONCLUSIONS: In terms of kinds of AMP, the guidelines were almostly
      followed in all operative procedures. However, the duration of AMP administration
      were longer than those recommended by the guidelines. On revision of "Japanese
      guidelines for prevention of perioperative infections in urologic field (2006)",
      these data would be taken into consideration to avoid dissociation between the
      guidelines and the practical side in the urologists.

PMID- 23971367
TI  - [Causes and salvage of failed urethroplasties for traumatic urethral injury].
AB  - OBJECTIVES: Salvage urethroplasty after failed repair of traumatic urethral
      injury is a urological challenge, and we herein describe our experience with it.
      METHODS: From October 2010 to January 2012, five patients underwent salvage
      repair of failed urethroplasties for traumatic urethral injuries: three bulbar
      straddle injuries and two pelvic fracture urethral injuries. One of the three
      failed urethroplasties for bulbar straddle injuries was a stricture excision and
      primary anastomosis, and its failure was due to periurethral abscess formation.
      Another was an augmented anastomotic urethroplasty using buccal mucosa, and its
      failure was due to periurethral abscess formation. The third was a tube graft
      urethroplasty using buccal mucosa, and its failure was due to a stricture at the
      anastomotic site. Two failed urethroplasties for pelvic fracture urethral
      injuries were perineal anastomotic repairs combined with corporal separation and
      inferior pubectomy, and the failures of both were due to ischemic bulbar
      necrosis. The urethral gap lengths estimated from urethrograms ranged from 12 to
      45 mm (mean = 26 mm). RESULTS: Urethroplasties in all patients with bulbar
      straddle injuries were salvaged by stricture excision and primary anastomosis
      with corporal separation, and urethroplasties in both patients with pelvic
      fracture urethral injuries were salvaged by abdominal transpubic perineal
      urethroplasty. Although the patients who underwent transpubic urethroplasty had
      transient pelvic girdle pain, no severe complications were observed. All patients
      were for 10 to 25 months postoperatively (mean = 16 months) able to void
      satisfactorily without additional treatment. CONCLUSIONS: Failed urethroplasties
      for traumatic urethral injuries can be salvaged with a second reconstruction
      surgery. The procedure of choice for this salvage is anastomotic urethroplasty
      with techniques for tension-free anastomosis.

PMID- 23971368
TI  - [Changes in life styles of pregnant women and risks for having a pregnancy
      afflicted with spina bifida].
AB  - AIMS: Though periconceptional intakes of folic acid could prevent the occurrence
      of spina bifida by 50 to 70%, the prevalence has not shown any decreasing
      tendency during the past 30 years in Japan. We aim to analyze various parameters
      through life style questionnaires and 3-day food records obtained from pregnant
      women the last 10 years, and to examine whether their life styles have been
      shifting to the direction of lowering the incidence of spina bifida. MATERIALS
      AND METHODS: Life style questionnaires inquired of knowledge of folic acid in
      relation to preventing spina bifida during a pregnancy and other relevant
      parameters, which were collected from 11,861 participants during a period of from
      2002 to 2011. Food records asked participants to semi-quantitatively describe
      diets and beverages they consumed for a 3-day period, which were collected from
      1,081 pregnant women from 2003 to 2011. RESULTS: Life style questionnaires
      demonstrated that knowledge of folic acid and the proportion of those who took
      folic acid supplements elevated from 15.3 and 9.1% in 2002 to 43.7 and 61.5% in
      2011, respectively, that comparison of those who took folic acid supplements from
      2008 to 2011 residing in one of 8 districts of Japan showed a significant
      difference, i.e., the proportion of those in the Chugoku or Kyushu district being
      significantly lower compared to that in the Hokkaido district, and that other
      life style parameters have not much altered the past 9 years, e.g., those who
      conceived as planed being 67%, those who confirmed own pregnancy within 6 weeks
      of pregnancy being 70%, those who took balanced diets being 65%, and those who
      did not smoke or drink being 95% and 96%, respectively. Three-day food records
      revealed that the mean dietary folate intakes ranged from 260 to 360 microg/day
      in each year which were less than the recommended dietary allowance (RDA)
      publicized by the government, but that the proportion of pregnant women in the
      first trimester who consumed folic acid supplements from 4 weeks prior to to 12
      weeks after conception increased from 7.4% in 2003 to 69.6% in 2011. CONCLUSIONS:
      As a whole it could be stated that life styles of pregnant women have been
      shifting toward the direction the past 10 years where the risk for having a
      pregnancy afflicted with spina bifida is to be decreased. Medical doctors,
      nurses, midwives, dietitians and pharmacists are asked to repeatedly supply
      important information on folic acid and to advise taking folic acid supplements
      400 microg a day to women planning to conceive or women in the reproductive age.

PMID- 23971369
TI  - [Treatment of hemodialyzed patient by targeted therapy in metastatic renal cell
      carcinoma: a case report].
AB  - Experience with treatment of hemodialyzed patients by targeted therapy is limited
      to the few cases reported. Little information has been provided on the safety and
      toxicity profile of temsirolimus and sorafenib when administered in hemodialyed
      patients with renal cell carcinoma (RCC). Herein, we report an RCC patient
      undergoing hemodialysis treated with temsirolimus and sorafenib for 16 months.
      The patient was a 69-year-old man who was diagnosed with right RCC. He underwent
      nephrectomy for a pT1b tumor in December 2002. Hemodialysis was introduced in
      July 2003 (7 months after nephrectomy). Seven years later, CT showed
      retroperitoneal nodal metastases. He was started on temsirolimus. Although 8
      cycles of this therapy were done, we discontinued it because of progressive
      disease. The CTCAE (Common Terminology Criteria for Adverse Events) grade 3
      adverse events were thrombopenia, but no adverse events of grade 4 or greater
      developed. Secondly, he was started on sorafenib. CT showed a partial response
      with a 45% decrease in tumor bulk using RECIST (Response Evaluation Criteria in
      Solid Tumors) criteria. He has partial response for 13 months. He presented high
      blood pressure requiring pharmacological treatment, but no adverse events of
      grade 4 or greater developed. Patients with terminal renal failure can be offered
      temsirolimus and sorafenib treatment with close clinical and laboratory
      monitoring. Treatment of RCC patient undergoing hemodialysis by targeted therapy
      appears to be feasible and effective.

PMID- 23971370
TI  - [Complete remission by sorafenib for local reccurence of renal cell carcinoma
      with a tempraly elevation of C-reactive protein: a case report].
AB  - A 66-year-old man appeared with a local recurrence of RCC 9 months after
      nephrectomy (clear cell carcinoma > sarcomatoid carcinoma, G2 > 3, pT3a). A
      tempraly elevation of serum C-reactive protein (CRP) appeared on administration
      of sorafenib and decrease of vascularity of the tumor was found on CT. After 13
      months of sorafenib administration the recurrent tumor disappeared completely and
      serum CRP was normalized concomitantly. He currently remains in complete
      remission for 37 months.

PMID- 23971371
TI  - [A case of aggressively growing bladder cancer in patient with long-term
      cystostomy due to spinal cord injury].
AB  - The patient was a 38-year-old man. A cystostomy catheter had been inserted when
      he was 23 years of age for neuropathic bladder due to cervical spinal cord injury
      at 20 years of age. Purulent discharge from around the cystotomy had continued
      for approximately 4 months. Examination revealed the formation of a subcutaneous
      tumor around the cystostomy, with elevated carcinoembryonic antigen (CEA) levels
      (459.4 ng/ml) in the blood. Urothelial carcinoma was detected using open biopsy.
      It was considered that primary urothelial carcinoma of the bladder had progressed
      along the cystostomy, and clinical stage 4 cT4N2M0 was diagnosed, with
      intrapelvic lymph node metastasis evident on imaging. Four courses of gemcitabine
      cisplatin chemotherapy were administered; a partial response was obtained, after
      which cystectomy and ileal conduit formation were performed with the main aim of
      improving difficulty in urination. However, retroperitoneal lymph node and liver
      metastases were observed 1 month postoperation with rapid enlargement; the
      patient died approximately 2 months after the surgery. The CEA level was observed
      to be 18,998 ng/ml before he died. Here, we have reported this case with a
      discussion of the literature concerning the association between long-term
      indwelling catheter in patients with spinal cord injury and the development of
      bladder cancer.

PMID- 23971372
TI  - [Neobladder-rectal fistula as early postoperative complication of radical
      cystectomy and orthotopic neobaldder construction].
AB  - We report a case of neobladder-rectal fistula that developed as an early
      postoperative complication of radical cystectomy and orthotopic neobladder
      construction procedures. A 75-year-old man underwent a radical cystectomy and
      orthotopic neobladder construction using Studer's method for locally invasive
      bladder cancer (cT2N0M0). The patient had severe watery diarrhea on postoperative
      day 20, and was diagnosed with a neobladder-rectal fistula based on cystography
      findings. We inserted a Foley catheter into the neobladder, and performed
      conservative treatment. Four months after development of the fistula, cystography
      revealed that it had spontaneously closed. A neobladder-rectal fistula is an
      extremely rare complication, with no other known reports. Herein, we present this
      case of neobladder-rectal fistula and discuss its formation, diagnosis and
      treatment, along with reference to previous reports of neobladder-vaginal
      fistulas.

PMID- 23971373
TI  - [Three cases of IgG4-related disease associated with urinary tract obstruction].
AB  - IgG4-related disease (IgG4RD) is a novel clinical entity characterized by tissue
      infiltration of IgG4-positive plasma cells. We report here 3 cases of IgG4RD
      associated with urinary tract obstruction. Patient 1 was a 59-year-old male who
      complained of difficulty on urination. A CT scan showed bilateral ureteral wall
      thickness, hydronephrosis, and an enlarged prostate. His serum IgG4 was 817
      mg/dl. We made a diagnosis of IgG4RD and performed bilateral ureteral stenting
      and steroid therapy. A significant reduction in the size of the lesion was
      detected, and IgG4 was decreased to 272 mg/dl. He was doing well after removal of
      the ureteral stent. Patient 2 was a 51-year-old female who complained of
      bilateral swelling of the submaxillary gland. A CT scan showed left ureteral wall
      thickness and hydronephrosis. Her serum IgG4 was 1,020 mg/dl. We made a diagnosis
      of IgG4RD and performed left ureteral stenting and steroid therapy. A significant
      reduction in the size of the lesion was detected, and IgG4 was decreased to 337
      mg/dl. She was doing well after removal of the ureteral stent. Patient 3 was a 64
      year-old male who underwent evaluation for autoimmune pancreatitis. He complained
      of back pain and bilateral hydronephrosis was detected. His serum IgG4 level was
      649 mg/dl. Bilateral ureteral stenting was performed based on a diagnosis of
      IgG4RD. He did not receive steroid therapy because of poorly-controlled diabetes
      mellitus. After insertion of the ureteral stent, hydronephrosis and back pain
      were relieved. We could only find a few case reports in the literature on IgG4RD
      associated with urinary tract obstruction. It is important for clinicians to bear
      in mind that IgG4RD sometimes causes urinary tract obstruction.

PMID- 23971374
TI  - MNA exercises its political strength.

PMID- 23971375
TI  - Nurses take action throughout Michigan.

PMID- 23971376
TI  - UMPNC, PECSH contracts secure rights, benefits for years to come.

PMID- 23971377
TI  - MNA wins back pay for 51 nurses at McLaren Lapeer Region.

PMID- 23971378
TI  - "Illness doesn't take a vacation" expand Medicaid now!

PMID- 23971379
TI  - Lori Batzloff, RN.

PMID- 23971380
TI  - Mental health: the current crisis and what nurses must know.

PMID- 23971381
TI  - [Apropos of the impact factor].

PMID- 23971382
TI  - [Report of the seminal characteristics in patients with consecutive pregnancy to
      intrauterine insemination and his perinatal complications].
AB  - BACKGROUND: It is reported that pregnancies achieved through assisted
      reproductive techniques have increased risk of complications. There is doubt as
      to whether this increase is attributable to the underlying infertility or to the
      assisted reproduction techniques. Postcapacitation seminal parameters have been
      mentioned as determinants of success. OBJECTIVES: To describe semen parameters of
      patients at the Mexican Fertility Center (CEPAM) who achieved pregnancy with
      intrauterine insemination and compare the causes of perinatal morbidity and
      mortality with those of the general population. PATIENTS AND METHODS: A
      descriptive, retrospective (2004-2009), analytical and longitudinal study based
      on analysis of intrauterine insemination cycles that achieved pregnancy with
      prenatal care and childbirth. The variables studied were: pregnancy, obstetric
      complications and postcapacitation semen parameters. For the analysis the data
      was divided according to sperm morphology. The results were analyzed using SPSS
      20. Continuous variables were reported as means, and their standard deviations
      and logistic regression as univariate to determine the statistical significance.
      The categorical variables were evaluated in frequencies and percentages. RESULTS:
      133 cases were analyzed, 78% with normal morphology over 4%, mean semen
      parameters: 0.63 mL volume, density 82.72 million/mL, progressive motility 88.5%
      and normal morphology over 4% of 5.93%. The 16.6% of pregnancies were twins.
      18.5% was abortion, 69% was cesarean section and 30% vaginal delivery. No
      differences were found in any of the variables when comparing normal sperm
      morphology groups lower and higher than 4%, except in patients with abortion.
      There was no increased incidence of perinatal complications than in the general
      population. CONCLUSIONS: Perinatal complications incidence is similar to the
      general population, except in multiple pregnancy. There is more success in
      intrauterine insemination when the postcapacitation morphology is over 4%.

PMID- 23971383
TI  - [Clinical comparision of alpha dihydroergocryptine against cabergoline in the
      treatment of the fibrocystic mastopathy].
AB  - BACKGROUND: Fibrocystic breast disease is one of the most frequent conditions of
      the breast among women from 30 to 49 years, with a frequency of about 60%, hence
      the interest in studying and treating it with the most advanced and effective
      resources. OBJECTIVE: To compare the efficacy and adverse events of alpha
      dihydroergocryptine with cabergoline in patients with fibrocystic breast disease.
      MATERIAL AND METHODS: A prospective, longitudinal, open, comparative study
      between alpha-dihydroergocryptine and cabergoline, made in the service of
      Gynecology and Obstetrics at the Dr. Miguel Silva General Hospital in Morelia,
      Michoacan. 171 patients diagnosed with fibrocystic breast disease were randomly
      assigned to the alpha-dihydroergocryptine or the cabergoline group. Assessments
      were made at baseline and every month subsequently. The following symptoms were
      evaluated: breast tenderness, breast pain, lumps and nipple discharge. The
      concentrations of prolactin were determined and an ultrasound was performed at
      baseline and at 3 and 6 months, patients were questioned about adverse events.
      RESULTS: 171 patients were included (81treated with alpha-dihydroergocryptine and
      90 with cabergoline); 156 completed the study. The age limits were 18 and 51
      years. The evolution time prior to study entry was 17.71 +/- 18.3 months for the
      alpha-dihydroergocryptine group and 18.57 +/- 20.35 for the cabergoline group. 15
      patients discontinued treatment due to adverse events (8 of the alpha
      dihydroergocryptine group and 7 of the cabergoline group). The most common
      adverse event was headache. CONCLUSIONS: In this study alpha-dihydroergocryptine
      was better tolerated and had better clinical response compared with cabergoline;
      breast pain and breast tenderness disappeared within the first month of
      treatment. Adverse events were similar for both treatments.

PMID- 23971384
TI  - [Evaluation of treatment of iron deficiency anemia in pregnancy].
AB  - BACKGROUND: Pregnancy is a condition that predisposes women to anemia, a problem
      which is easily solved with the identification of susceptible patients and with
      proper treatment. OBJECTIVE: To determine the prevalence of anemia in the study
      group, the characteristics of the patients, and assess the impact of iron therapy
      in anemic pregnant women. MATERIAL AND METHODS: A retrospective study was done in
      98 pregnant patients who attended a medical office in San Luis Potosi, S.L.P,
      between 2010 and 2011. The studied variables were: hemoglobin and hematocrit
      concentration for anemia diagnosis. Statistical analysis was performed using Epi
      Info-7 for the association between variables. RESULTS: The prevalence of anemia
      found in the study was 4.08% in the first weeks of gestation. 75% of those
      patients were overweight or obese, and as the pregnancy progressed prevalence
      increased to 16.32%. The patients whose anemia was detected between weeks 28-33
      of gestation had 4.58 times the risk of having it than those who were detected in
      the first trimester (p < .05). While anemia was more frequent among women with
      overweight or obesity 5% (n = 3), no statistically significant difference with
      normal weight women was observed in early pregnancy. CONCLUSIONS: The prevalence
      of anemia increased as pregnancy progressed, therefore It is necessary that the
      physician requests the patient 3 or 4 blood studies to keep adequate prenatal
      care and have the opportunity for early detection of anemia.

PMID- 23971385
TI  - [Diagnostic hysteroscopy indications and results in Complexo Hospitalario
      Universitario De Ourense].
AB  - BACKGROUND: Diagnostic hysteroscopy is an endoscopic technique that allows the
      evaluation of the endocervical canal and uterine cavity. OBJECTIVE: To evaluate
      indications, complications and referral to operative hysteroscopy. To analyze the
      correlation between sonographic display, hysteroscopy findings and histological
      diagnosis. MATERIALS AND METHODS: Retrospective and descriptive study of 904
      patients who underwent diagnostic hysteroscopy between January 1, 2008 and June
      30, 2012. RESULTS: The most frequent indication was sonographic detection of
      endometrial polyps (75% were premenopausal and 71.2% postmenopausal). The
      complication rate associated with the test was 11.4%. The reduction experimented
      in operative hysteroscopies was from 31.2% in 2008 to 12.2% between January and
      June 2012. When a polyp or a myoma was detected by sonography, diagnostic
      hysteroscopy showed them in 64.4% y 62.5% of the cases, respectively. The
      correlation between hysteroscopic findings and histopathologic diagnosis was
      77.7% for normal endometrium, 77.9% for polyps, 17.8% for hyperplasic appearance
      and 100% for carcinoma suspicion. CONCLUSIONS: Diagnostic hysteroscopy is a safe
      technique that allows small interventions avoiding operative hysteroscopies.
      There is a good relation between hysteroscopic visual inspection and
      anatomopathologic diagnosis, but biopsy should be taken except if normal
      endometrium is visualized.

PMID- 23971386
TI  - [The role of the computed tomography in the identification of the syndrome of
      pelvic congestion].
AB  - BACKGROUND: Pelvic congestion syndrome is a condition not yet fully understood,
      hence provokes controversy. It is cause of up to 40% of visits to the doctor;
      affecting women of reproductive age who experience non-specific symptoms such as
      characteristic pelvic pain with more than six months of evolution and difficult
      to treat dyspareunia in which even narcotics are insufficient for control.
      OBJECTIVE: To recognize the vascular anatomy of the pelvic cavity and identify
      the characteristics of pelvic congestion syndrome demonstrable by computed
      tomography. MATERIAL AND METHODS: A descriptive, observational, cross-sectional
      and retrospective study at Hospital Angeles del Pedregal, in the Department of
      Radiology and Imaging with patients who reported imaging studies with key
      findings to recognize the pelvic congestion syndrome. All women with incidental
      finding of abnormal dilation of the gonadal vein were included, allowing to
      suggest pelvic congestion syndrome as a possible diagnosis. RESULTS: There were
      17 cases (0.9%) of patients with abdominopelvic pain syndrome who underwent
      multislice computed tomography to 3 mm, with extension from the lung bases to the
      pubic symphysis. Predominance of left gonadal vein is conditioned by the
      anatomical arrangement of the left gonadal vein. During the arterial phase
      opacification of the gonadal vein was identified in 11 patients (65%), a
      circumstance that correlates with retrograde venous flow valve incompetence. In
      computed tomography findings of pelvic congestion syndrome were also identified
      12 patients (70%) with abdominopelvic pain syndrome. CONCLUSIONS: Pelvic
      congestion syndrome is a rare condition that radiologists do not consider because
      they don't know it and the clinical diagnoses give no clinical data to suggest
      this condition. But if one takes into account the literature, it refers to it as
      the origin of up to 40% of the visits to the gynecologist, and there may be more
      cases that will increase its prevalence.

PMID- 23971387
TI  - [Case report. Aggressive angiomyxoma of vagina. A rare tumor diagnosed].
AB  - The case of a female patient of 35 years of age, with a pedunculated tumor
      dependent of the vagina, of approximately 25 x 12 x 8 cm, who had a wide
      resection. The report was consistent with myxoid aggressive angiomyxoma. This is
      a myxoid mesenchymal neoplasm of slow growth, which mainly appears in deep soft
      tissues of the pelvic, genital or perineal areas of adult women. It is usually
      diagnosed after surgical resection by histopathologic examination. Routine
      evaluation includes: complete physical examination, imaging and pathology report
      of diagnostic confirmation.

PMID- 23971388
TI  - [Pregnancy and Fallot tetralogy without surgical correction: report of a case].
AB  - Tetralogy of Fallot is the most common cyanotic congenital heart disease. Women
      with this condition may become pregnant, and it is important to detect the
      disease to prevent cardiovascular complications and to reduce maternal and fetal
      death. The purpose of this paper is to report the case of a pregnant patient with
      no previous diagnosis of uncorrected tetralogy of Fallot, who reached the end of
      pregnancy with added diagnoses of severe preeclampsia and HELLP syndrome. For
      accurate information about the natural history of tetralogy of Fallot it is
      necessary to review the literature of the past 30 years because there is no
      recently published series. It is common for patients with tetralogy of Fallot and
      pregnancy to suffer a gradual increase in the severity of pulmonary stenosis,
      with exacerbation of symptoms and increased cyanosis. The long-term prognosis is
      extremely poor in the absence of correction, with a mortality of 10%.

PMID- 23971389
TI  - [Conservative treatment of subcapsular hematoma in preeclampsia and HELLP
      syndrome: a case report].
AB  - BACKGROUND: Liver hematoma is a rare and serious complication of pregnancy
      associated with preeclampsia-eclampsia and HELLP syndrome. CASE REPORT: 27 years
      old patient with two pregnancies, first pregnancy with eclampsia, admitted with
      36.5 weeks of gestation, blood pressure of 140-100 mmHg, epigastric pain,
      shoulder pain without peritoneal irritation and increased tendon reflexes. The
      requested preeclamptic profile supports the diagnosis of severe preeclampsia and
      HELLP syndrome. It was decided to terminate the pregnancy by abdominal route.
      Male product was obtained alive, 2,060 g, Apgar 8/9, gestational age of 38.2
      weeks Capurro. A review did not report liver parenchymal. The evolution during
      mediate puerperium was torpid, the patient presented epigastric pain and shoulder
      pain, and there was a rise in transaminases (AST 687 U/L, ALT 813 U/L),
      progressive thrombocytopenia (113, 103/ pL), decreased hemoglobin, proteinuria
      and hypovolemic shock. Abdominal CT scan was requested, and it confirmed a
      heterogeneous liver image (117 x 85 x 104 mm) with a volume of 694 cc, suggesting
      hepatic hematoma. Serialized control of abdominal CT indicated liver hematoma
      resorption after 25 days of hospitalization. Seven days after discharge
      transaminase levels were normal. CONCLUSION: To consider in the diagnosis of
      preeclampsia and HELLP syndrome the likelihood of liver hematoma as an acute
      complication; early treatment improves the prognosis.

PMID- 23971390
TI  - [Hidradenoma papilliferum. Report of two cases and review of literature].
AB  - We bring two cases of hidradenoma papilliferum, rare injury. We describe the
      clinical, histopathological and a review of the available literature on the
      condition.

PMID- 23971391
TI  - [Uterine spontaneous secondary perforation to pyometra in a patient with
      cervicouterine cancer: report of a case].
AB  - The pyometra is a rare condition, with an incidence of less than 1%. In patients
      with cervical cancer, spontaneous rupture of pyometra manifests as a generalized
      peritonitis, which is extremely rare, in the literature only seven cases are
      described. This paper reports the case of a patient with a history of
      postmenopausal vaginal bleeding one month before her admission to the hospital;
      she attended because of acute abdomen. The CT scan reported air in the abdominal
      cavity and the uterus with air at the periphery, so she underwent an exploratory
      laparotomy in which purulent material was found with two perforations in the
      uterine fundus. She underwent total abdominal extrafacial hysterectomy with
      histopathological diagnosis of keratinizing squamous cell carcinoma, moderately
      differentiated.

PMID- 23971392
TI  - [Valuation of the clinical methods in the study of the bony pelvis. 1958].

PMID- 23971393
TI  - [A purpose of examination oral].

PMID- 23971394
TI  - Ohio rolls out welcome mat for physician inventors.

PMID- 23971395
TI  - Avatars, robots, and computers are coming to primary care.

PMID- 23971396
TI  - Q & A with Lucian Leape. Interview by Carrie Johnson.

PMID- 23971397
TI  - Wisdom through failure: exemplary physicians discuss their regrets.

PMID- 23971398
TI  - Quantifying quality care isn't easy.

PMID- 23971399
TI  - Sustainability: a fiduciary responsibility of senior leaders?

PMID- 23971400
TI  - Keys to success for department chairs and section heads.

PMID- 23971401
TI  - How quickly do clinicians adopt EMR notes?

PMID- 23971402
TI  - Clinically integrated networks: vision, purpose and development.

PMID- 23971403
TI  - Making SMART goals smarter.

PMID- 23971404
TI  - Busting six myths about military-trained health care professionals.

PMID- 23971405
TI  - Finding my blind spot as a physician leader.

PMID- 23971406
TI  - Elephant-based medicine.

PMID- 23971407
TI  - Matrix suppression as a guideline for reliable quantification of peptides by
      matrix-assisted laser desorption ionization.
AB  - We propose to divide matrix suppression in matrix-assisted laser desorption
      ionization into two parts, normal and anomalous. In quantification of peptides,
      the normal effect can be accounted for by constructing the calibration curve in
      the form of peptide-to-matrix ion abundance ratio versus concentration. The
      anomalous effect forbids reliable quantification and is noticeable when matrix
      suppression is larger than 70%. With this 70% rule, matrix suppression becomes a
      guideline for reliable quantification, rather than a nuisance. A peptide in a
      complex mixture can be quantified even in the presence of large amounts of
      contaminants, as long as matrix suppression is below 70%. The theoretical basis
      for the quantification method using a peptide as an internal standard is
      presented together with its weaknesses. A systematic method to improve
      quantification of high concentration analytes has also been developed. 

PMID- 23971409
TI  - "Geriatricizing" hospitalists: identifying educational opportunities.
AB  - The objective of this study was to identify differences between geriatricians and
      hospitalists in caring for hospitalized older adults, so as to inform faculty
      development programs that have the goal of improving older patient care. Eleven
      hospitalists and 13 geriatricians were surveyed regarding knowledge, confidence,
      and practice patterns in caring for hospitalized older adults, targeting areas
      previously defined as central to taking care of older hospitalized patients.
      Overall, geriatricians had more confidence and more knowledge in caring for older
      hospitalized adults. The areas in which hospitalists expressed the least
      confidence were in caring for patients with dementia, self-care issues, and care
      planning. Geriatricians reported more routine medication reviews, functional and
      cognitive assessments, and fall evaluations. Geriatricians and hospitalists
      differ in their approach to older adults. Where these differences reflect lack of
      knowledge or experience, they set the stage for developing curricula to help
      narrow these gaps. 

PMID- 23971408
TI  - Quantitative proteomics reveals oxygen-dependent changes in neuronal mitochondria
      affecting function and sensitivity to rotenone.
AB  - Mitochondria are implicated in a variety of degenerative disorders and aging.
      Mitochondria are responsive to the oxygen in their environment, yet tissue
      culture is performed at atmospheric (21%) oxygen and not at physiological (1-11%)
      oxygen levels found in tissues. We employed imaging of mitochondrial probes, mass
      spectrometry, Western blots, and ATP assays of the human neuroblastoma cell-line
      SH-SY5Y and imaging of mitochondrial probes in human primary neurons under
      standard nonphysiological oxygen conditions (atmospheric) and under physiological
      oxygen levels in the nervous system to assess the impact of oxygen on
      mitochondrial function. SH-SY5Y cells cultured in physiological 5% oxygen
      exhibited the lowest reactive oxygen species (ROS) production, indicating that
      culture at 5% oxygen is favored; these results were mimicked in primary human
      cells. Mass spectrometric analysis revealed extensive mitochondrial proteomic
      alterations in SH-SY5Y cells based on oxygen culture condition. Among these, the
      rotenone-sensitive subunit of complex I NDUFV3 was increased in cells cultured at
      5% oxygen. Rotenone is a Parkinson's disease-linked toxin, and correspondingly SH
      SY5Y cells cultured at 5% oxygen also exhibited over 10 times greater sensitivity
      to rotenone than those cultured in atmospheric, 21%, oxygen. Our results indicate
      that neuronal mitochondria are responsive to oxygen levels and produce
      differential responses under different oxygen levels. 

PMID- 23971410
TI  - Nerve growth factor (NGF) levels in follicular fluid of infertile patients
      undergoing to in vitro fertilization (IVF) cycle.
AB  - OBJECTIVE: The aim of this study was to determine the levels of NGF in follicular
      fluid and serum samples, and to correlate them with some characteristics of the
      patients (age) and of the IVF protocol (E2 levels, number of collected oocytes,
      used FSHr IU) to investigate its rule in the folliculogenesis. METHODS: This
      study examined a sample of 78 women undergoing to FIVET/ICSI cycles since October
      2011 to March 2013. NGF levels were determinated in follicular fluid (FF) and
      serum sample using enzyme immunoassay ELISA kit for NGF. RESULTS: The NGF level
      was significantly higher in FF (213.76 pg/ml) than in basal serum (46.47 pg/ml (p
      < 0.001) and in serum sample of the pick-up day (60.75 pg/ml (p < 0.001). In FF,
      the levels of NGF were positively correlated to age of women (corr.coeff. r =
      0.44) and units of FSHr used during stimulation protocol (corr.coeff r = 0.34).
      DISCUSSION: Our results demonstrate that the FF levels are higher than the blood;
      so there is a local production of NGF in the ovarian follicle, important for the
      follicle's growth and oocyte quality. We could also say that the increase of NGF
      levels is correlated to a lower ovary response, that is obviously less in the
      older women.

PMID- 23971411
TI  - Environmental investigation following the first human case of babesiosis in
      Tennessee.
AB  - Babesiosis is an emerging tick-borne zoonotic disease in the United States caused
      by Babesia parasites. In 2009, the first case of babesiosis was documented in
      Tennessee. Environmental investigation at the reported site of tick exposure
      included collection of ticks and specimens from eastern cottontail rabbits
      (Sylvilagus floridanus) and white-tailed deer ( Odocoileus virginianus ) that
      were tested for piroplasms by molecular and serologic methods. One hundred and
      sixty-six Ixodes scapularis ticks and biological samples from 8 rabbits and 5
      deer were collected. Ixodes scapularis were PCR positive for Babesia odocoilei (n
      = 7, 4%) and Theileria cervi (n = 24, 14%). Deer were seropositive for B.
      odocoilei and PCR positive for T. cervi. Rabbits were seropositive for B.
      odocoilei and Babesia sp. MO1, and 1 rabbit was PCR positive for Babesia sp. MO1.
      In summary, zoonotic Babesia sp. MO1 infection in rabbits is reported here for
      the first time in Tennessee as well as infection of deer and I. scapularis ticks
      with 2 other piroplasms of veterinary importance.

PMID- 23971412
TI  - Molecular dynamics simulations of small halogenated organics at the air-water
      interface: implications in water treatment and atmospheric chemistry.
AB  - Free energy profiles associated with transfer of chlorinated and brominated
      halomethane molecules from the gas phase across the water-vapor interface to the
      aqueous phase were calculated using classical molecular dynamics simulations. The
      investigated species include chloromethane (CH3Cl), bromomethane (CH3Br),
      dichloromethane (CH2Cl2), dibromomethane (CH2Br2), chloroform (CHCl3), and
      bromoform (CHBr3). The employed halomethane force field was tuned by scaling up
      the atomic charges to reproduce the experimental hydration free energies. The
      computed free energy profiles have a minimum at the water-vapor interface of
      about 12-15 kJ.mol(-1) relative to full hydration in the bulk liquid. This
      implies that the halomethanes exhibit enhanced interfacial concentrations in
      systems with large surface area per unit volume, such as air bubbles dispersed in
      water or water droplets dispersed in air. Implications for water treatment as
      well as for atmospheric chemistry are discussed. 

PMID- 23971413
TI  - Magnetic, acidic, ionic liquid-catalyzed one-pot synthesis of spirooxindoles.
AB  - Magnetic, supported, acidic ionic liquid was synthesized and identified as an
      efficient catalyst for the one-pot synthesis of novel spirooxindole derivatives
      at mild conditions and in good yields. Three component reaction of wide variety
      of substituted isatins, 1,3-dimethyl-2-amino uracil, and barbituric acid,
      thiobarbituric acid, and dimedon as 1,3-dicarbonyl compounds gives the target
      compounds. Operational simplicity, low cost, high yields, environmental
      friendliness, wide applicability and reusability and easy recovery of the
      catalyst using an external magnet are the key features of this methodology. 

PMID- 23971415
TI  - Is it relevant? Influence of trial manipulations of prospective memory context on
      task interference.
AB  - Prospective memory (PM) research has often investigated if having an intention
      interferes with ongoing activities, but rarely by linking the intention to a
      particular context. We examined effects of trial-by-trial changes in whether the
      context (defined by colour) was relevant for the nonfocal PM task. The ongoing
      task involved speeded decisions about the position (left/right) of the upper-case
      letter in a pair, and the PM task consisted of pressing an additional key if the
      upper-case and lower-case letters were in a specified colour and the same letter.
      Trials switched between two colours either randomly or predictably in eight-trial
      blocks. We also manipulated the presence/absence of occasional same-letter pairs
      in the irrelevant context. Results showed higher cost of having a nonfocal PM
      task when ongoing stimuli matched than when they mismatched the target's colour.
      Moreover, cost for intention-irrelevant stimuli was minimized, though never
      eliminated, by blocking match/mismatch trials. These findings highlight the role
      that local changes in intention-related context play in task interference and
      support a view of monitoring as a flexible mechanism. Additionally, the study
      introduced a novel way of embedding intention-related events in the irrelevant
      context shortly before the occurrence of PM targets, with results tentatively
      suggesting that such events might impair target detection.

PMID- 23971414
TI  - Anti-inflammatory and immunomodulatory mechanisms of mesenchymal stem cell
      transplantation in experimental traumatic brain injury.
AB  - BACKGROUND: Previous studies have shown beneficial effects of mesenchymal stem
      cell (MSC) transplantation in central nervous system (CNS) injuries, including
      traumatic brain injury (TBI). Potential repair mechanisms involve
      transdifferentiation to replace damaged neural cells and production of growth
      factors by MSCs. However, few studies have simultaneously focused on the effects
      of MSCs on immune cells and inflammation-associated cytokines in CNS injury,
      especially in an experimental TBI model. In this study, we investigated the anti
      inflammatory and immunomodulatory properties of MSCs in TBI-induced
      neuroinflammation by systemic transplantation of MSCs into a rat TBI model.
      METHODS/RESULTS: MSCs were transplanted intravenously into rats 2 h after TBI.
      Modified neurologic severity score (mNSS) tests were performed to measure
      behavioral outcomes. The effect of MSC treatment on neuroinflammation was
      analyzed by immunohistochemical analysis of astrocytes, microglia/macrophages,
      neutrophils and T lymphocytes and by measuring cytokine levels [interleukin (IL)
      1alpha, IL-1beta, IL-4, IL-6, IL-10, IL-17, tumor necrosis factor-alpha,
      interferon-gamma, RANTES, macrophage chemotactic protein-1, macrophage
      inflammatory protein 2 and transforming growth factor-beta1] in brain
      homogenates. The immunosuppression-related factors TNF-alpha stimulated
      gene/protein 6 (TSG-6) and nuclear factor-kappaB (NF-kappaB) were examined by
      reverse transcription-polymerase chain reaction and Western blotting. Intravenous
      MSC transplantation after TBI was associated with a lower density of
      microglia/macrophages and peripheral infiltrating leukocytes at the injury site,
      reduced levels of proinflammatory cytokines and increased anti-inflammatory
      cytokines, possibly mediated by enhanced expression of TSG-6, which may suppress
      activation of the NF-kappaB signaling pathway. CONCLUSIONS: The results of this
      study suggest that MSCs have the ability to modulate inflammation-associated
      immune cells and cytokines in TBI-induced cerebral inflammatory responses. This
      study thus offers a new insight into the mechanisms responsible for the
      immunomodulatory effect of MSC transplantation, with implications for functional
      neurological recovery after TBI.

PMID- 23971416
TI  - Tetramethoxypyrene-based biradical donors with tunable physical and magnetic
      properties.
AB  - Synthesis of 2,7-disubstituted tetramethoxypyrene-based neutral biradical donors
      is reported. The biradicals were characterized by EPR, UV-vis, CV, SQUID, and
      single-crystal X-ray diffraction, and their optical, electrochemical, and
      structural properties were compared and discussed. The experimental results are
      well supported by DFT calculations. Systematic tuning of magnetic exchange
      interactions was achieved by varying the radical moieties. 

PMID- 23971417
TI  - The search for "common sense": an electrophysiological study of the comprehension
      of words and pictures in reading.
AB  - Event-related brain potentials (ERPs) from 26 scalp sites were used to
      investigate whether or not and, if so, the extent to which the brain processes
      subserving the understanding of imageable written words and line drawings are
      identical. Sentences were presented one word at a time to 28 undergraduates for
      comprehension. Each sentence ended with either a written word (regular sentences)
      or with a line drawing (rebus sentences) that rendered it semantically congruous
      or semantically incongruous. For half of the subjects regular and rebus sentences
      were randomly intermixed whereas for the remaining half the regular and rebus
      sentences were presented in separate blocks (affording within-subject comparisons
      in both cases). In both presentation formats, words and line drawings generated
      greater negativity between 325 and 475 msec post-stimulus in ERPs to incongruous
      relative to congruous sentence endings (i.e., an N400-like effect). While the
      time course of this negativity was remarkably similar for words and pictures,
      there were notable differences in their scalp distributions; specifically, the
      classic N400 effect for words was larger posteriorly than it was for pictures.
      The congruity effect for pictures but not for words was also associated with a
      longer duration (lower frequency) negativity over frontal sites. In addition,
      under the mixed presentation mode, the N400 effect peaked about 30 msec earlier
      for pictures than for words. All in all, the data suggest that written words and
      pictures when they terminate sentences are processed similarly, but by at least
      partially nonoverlapping brain areas. 

PMID- 23971418
TI  - Reduced Timing Variability in Patients with Unilateral Cerebellar Lesions during
      Bimanual Movements.
AB  - Timing variability on a repetitive tapping task was studied in subjects with
      unilateral cerebellar lesions. During unimanual tapping, within-hand variability
      was larger when tapping with the ipsilesional hand in comparison to tapping with
      the contralesional hand. However, variability in the impaired hand was greatly
      reduced when subjects tapped with two hands together. The improvement in within
      hand variability during bimanual tapping was associated with a reduction in
      central variability rather than response implementation variability according to
      the two-process model of Wing and Kristofferson (1973). It is proposed that (1)
      each half of the cerebellum independently regulates the temporal aspects of
      movements on the ipsilateral side and (2) temporal coupling constraints require
      these separate signals to be integrated prior to response implementation for
      bimanual movements. 

PMID- 23971419
TI  - Development of Schemata during Event Parsing: Neisser's Perceptual Cycle as a
      Recurrent Connectionist Network.
AB  - Neural net simulations of human event parsing are described. A recurrent net was
      used to simulate data collected from human subjects watching short videotaped
      event sequences. In one simulation, the net was trained on one-half of a taped
      sequence with the other half of the sequence being used to test transfer
      performance. In another simulation, the net was trained on one complete event
      sequence and transfer to a different event sequence was tested. Neural net
      simulations provide a unique means of observing the interrelation of top-down and
      bottom-up processing in a basic cognitive task. Examination of computational
      patterns of the net and cluster analysis of the hidden units revealed two factors
      that may be central to event perception: (1) similarity between a current input
      and an activated schema and (2) expected duration of a given event. Although the
      importance of similarity between input and activated schemata during event
      perception has been acknowledged previously (e.g., Neisser, 1976; Schank, 1982),
      the present study provides specific instantiation of how similarity judgments can
      be made using both top-down and bottom-up processing. Moreover, unlike other work
      on event perception, this approach provides a potential mechanism for how
      schemata develop. 

PMID- 23971420
TI  - Progressive Nonfluent Aphasia: Language, Cognitive, and PET Measures Contrasted
      with Probable Alzheimer's Disease.
AB  - The purpose of this study was to compare the language and cognitive profiles of
      four progressive nonfluent aphasia (PNFA) patients with 25 probable Alzheimer's
      disease (pAD) patients, and to identify the distinct cortical defects associated
      with cognitive deficits in PNFA using positron emission tomography (PET).
      Longitudinal observations of PNFA patients revealed progressively telegraphic
      speech and writing and a gradual deterioration of sentence comprehension, but
      memory and visual functioning were relatively preserved. Direct contrast with PAD
      patients revealed that PNFA patients are significantly impaired on grammatical
      phrase structure aspects of sentence comprehension and expression, phonemic
      judgments, repetition, and digit span, but not on other cognitive measures. PET
      studies of PNFA revealed reduced cortical activity throughout the left
      hemisphere. In addition, there was a prominent defect in left superior and middle
      temporal and inferior frontal regions of PNFA patients that differed
      significantly from the distribution of regional cerebral dysfunction in pAD. We
      conclude that PNFA is associated with a distinct profile of language and
      cognitive difficulty, and that this pattern of impairment is related to cortical
      dysfunction in a specific distribution of the left hemisphere. 

PMID- 23971421
TI  - Modulation of event-related potentials by semantic priming: effects of color-cued
      selective attention.
AB  - The processing nature of N400, an event-related brain potential (ERP) component
      associated with semantic processing, was investigated in a paradigm combining a
      semantic priming lexical decision task and color-cued selective attention.
      Semantic priming effects on ERPs and reaction time (RT) were examined when
      targets and preceding semantically related primes were either both attended or
      both unattended, and when only either the prime or target was the focus of
      attention. Priming effects were determined by comparing semantically primed
      target ERPs (and RTs when appropriate) to their prime (in those conditions where
      the prime and target had the same attentional status) and/or to an unprimed
      control target matched to the attentional status of the primed target. Control
      stimuli were examined for ERP effects of color-cued selective attention
      unconfounded by priming factors. Experiment 1 required overt responses to words
      and nonwords in a binary choice task, while Experiment 2 required response only
      to nonwords. RTs in Experiment 1 indicated facilitatory priming effects to all
      semantically primed attended targets. In Experiments 1 and 2 ERPs to primes and
      controls were consistently more negative than the primed target trace in the N400
      latency range in conditions with attended primes, suggesting priming effects on
      N400 are contingent on attentional processing of the prime. Removal of the
      attention manipulation (Experiment 3) resulted in an N400 component with a well
      defined peak not evident in the first two experiments, indicating modulation of
      N400 by overlapping effects of attention. 

PMID- 23971422
TI  - Neurological distribution of processing resources underlying language
      comprehension.
AB  - Using a cross-modal lexical priming technique we provide an on-line examination
      of the ability of aphasic patients to construct syntactically licensed
      dependencies in real time. We show a distinct difference between Wernicke's and
      Broca's aphasic patients with respect to this form of syntactic processing: the
      Wernicke's patients link the elements of dependency relations in the same manner
      as do neurologically intact individuals; the Broca's patients show no evidence of
      such linkage. These findings indicate that the cerebral tissue implicated in
      Wernicke's aphasia is not crucial for recovering syntactically licensed
      structural dependencies, while that implicated in Broca's aphasia is. Moreover,
      additional considerations suggest that the latter region is not the locus of
      syntactic representations per se, but rather provides the resources that sustain
      the normal operating characteristics of the lexical processing system
      characteristics that are, in turn, necessary for building syntactic
      representations in real time. 

PMID- 23971424
TI  - Cognitive science: an introduction.

PMID- 23971423
TI  - The development of intersensory perception: comparative perspectives.

PMID- 23971425
TI  - Marcus e. Raichle.
AB  - Marc Raichle is a Professor in the Departments of Radiology, Neurology, and
      Neurobiology at the Washington University School of Medicine. He is also a Senior
      Fellow in the McDonnell Center for Studies of Higher Brain Function at Washington
      University. He received a B.S. and M.D. from the University of Washington in
      Seattle and his training in neurology at the New York Hospital-Cornell University
      Medical College where he was introduced to research on brain circulation and
      metabolism by Fred Plum and Jerry Posner. He joined the faculty of Washington
      University in 1971 after serving 2 years in the United States Air Force at the
      School of Aerospace Medicine. His research has focused, broadly, on studies of
      the brain circulation and metabolism as a means of understanding human brain
      function in health and disease. He has been active in the development of
      cognitive neuroscience, serving since its inception as an advisor to the
      McDonnell-PEW Program in Cognitive Neuroscience. In his spare time he is an
      amateur oboe/English horn player, sailor, and recreational high-altitude
      physiologist. 

PMID- 23971428
TI  - Impulsivity and related neuropsychological features in regular and addictive
      first person shooter gaming.
AB  - Putative cyber addictions are of significant interest. There remains little
      experimental research into excessive use of first person shooter (FPS) games,
      despite their global popularity. Moreover, the role between excessive gaming and
      impulsivity remains unclear, with previous research showing conflicting findings.
      The current study investigated performances on a number of neuropsychological
      tasks (go/no-go, continuous performance task, Iowa gambling task) and a trait
      measure of impulsivity for a group of regular FPS gamers (n=25), addicted FPS
      gamers (n=22), and controls (n=22). Gamers were classified using the Addiction
      Engagement Questionnaire. Addicted FPS gamers had significantly higher levels of
      trait impulsivity on the Barratt Impulsiveness Scale compared to controls.
      Addicted FPS gamers also had significantly higher levels of disinhibition in a
      go/no-go task and inattention in a continuous performance task compared to
      controls, whereas the regular FPS gamers had better decision making on the Iowa
      gambling task compared to controls. The results indicate impulsivity is
      associated with FPS gaming addiction, comparable to pathological gambling. The
      relationship between impulsivity and excessive gaming may be unique to the FPS
      genre. Furthermore, regular FPS gaming may improve decision making ability.

PMID- 23971427
TI  - Overcoming barriers in evaluating outbreaks of diarrheal disease in resource poor
      settings: assessment of recurrent outbreaks in Chobe District, Botswana.
AB  - BACKGROUND: Diarrheal illness remains a leading cause of global morbidity and
      mortality, with the majority of deaths occurring in children <5 years of age.
      Lack of resources often prohibits the evaluation of outbreak characteristics and
      limits progress in managing this important disease syndrome, particularly in
      Africa. Relying only on existing medical staff and hospital resources, we assess
      the use of a questionnaire survey tool to identify baseline outbreak
      characteristics during recurrent diarrheal outbreaks in Chobe, Botswana. METHODS:
      Using historical surveillance data (2006-2009), the temporal pattern of recurrent
      diarrheal outbreaks was evaluated among patients <5 years of age presenting to
      health facilities in Chobe District. Using a questionnaire survey tool, medical
      staff from selected health facilities assessed patients (all ages) presenting
      with diarrheal disease during two diarrheal outbreaks (2011-2012). Cluster
      analysis and classification and regression trees (CART) were used to evaluate
      patient attributes by outbreak. RESULTS: We identified a bimodal, annual pattern
      of acute diarrhea in children <5 years of age across years (Wilcox test, W =
      456.5, p = 0.052). Historical outbreak periods appeared to coincide with major
      hydrological phenomena (rainfall/flood recession). Across health facilities, a
      significant percent of patients in the prospective study were in the >=5 age
      class (44%, n = 515 and 35%, n = 333 in the dry and wet season outbreaks,
      respectively). Cluster analysis of questionnaire data identified two main
      branches associated with patient age (<5 and >=5 years of age). Patients did not
      cluster by outbreak or village. CART examination identified sex and
      hospitalization as being most predictive of patients <5 years and household
      diarrhea in patients >=5 years. Water shortages and water quality deficiencies
      were identified in both outbreaks. CONCLUSIONS: Diarrhea is a persistent,
      seasonally occurring disease in Chobe District, Botswana. Lack of variation in
      outbreak variables suggests the possibility of environmental drivers influencing
      outbreak dynamics and the potential importance of human-environmental linkages in
      this region. Public health strategy should be directed at securing improved water
      service and correcting water quality deficiencies. Public health education should
      include increased emphasis on sanitation practices when providing care to
      household members with diarrhea. While global diarrheal disease surveillance is
      directed at the under-5 age group, this may not be appropriate in areas of high
      HIV prevalence such as that found in our study area where a large immune
      compromised population may warrant increased surveillance across age groups. The
      approach used in this study provided the first detailed characterization of
      diarrheal disease outbreaks in the area, an important starting point for
      immediate intervention and development of working hypotheses for future disease
      investigations. While data derived from this approach are necessarily limited,
      they identify critical information on outbreak characteristics in resource poor
      settings where data gaps continue and disease incidence is high.

PMID- 23971429
TI  - Pain assessment and treatment decisions for virtual human patients.
AB  - Laypeople and healthcare professionals use demographic cues when making pain
      management decisions. These decisions can negatively affect patient outcomes.
      This study examined whether laypeople base their pain management decisions in
      part on pain-related postures and demographic cues. Virtual human (VH) technology
      was used to research whether sex and race, as well as body posture, influenced
      pain management decisions. Ninety-seven laypersons examined VH patients
      exhibiting low back pain related body postures whose demographic cues varied by
      VH sex and VH race. T tests validated that participants were able to distinguish
      between high pain related body postures and low pain related body postures. The
      participants assessed male VH patients to be experiencing more pain than female
      VH patients. This study suggests that participants use sex as a cue when
      assessing pain. Participants may perceive VH male patients as experiencing high
      pain intensity if the participants are willing to counter male stereotypes and
      acknowledge that the male VH patients display pain behaviors.

PMID- 23971430
TI  - Reasons for playing casual video games and perceived benefits among adults 18 to
      80 years old.
AB  - Casual video games (CVGs) are becoming increasingly popular among middle-aged and
      older adults, yet there are few studies documenting why adults of different ages
      play these games, what benefits they perceive, and how regularly they play. The
      present study compared the online survey responses of 10,308 adults ranging from
      18 to 80 years of age to questions regarding PopCap's popular free online game,
      Bejeweled Blitz (BJB). All respondents cited playing against friends as their
      main reason for playing. However, there were differences by age in the second
      most frequently cited reason. Middle-aged adults cited stress relief, and older
      adults reported that they seek the game's challenges. As a result of playing
      CVGs, younger adults noted that they felt sharper and experienced improved
      memory; older adults were more likely to feel that their visuospatial skills and
      response time benefited. Adults aged 60 and older had heavier patterns of game
      play than did adults under the age of 60 years. A significant number of
      respondents (14.7%) spontaneously noted that they felt that BJB had addictive
      qualities. CVG players seem to be drawn into this activity by its social nature
      and to a certain extent by its reinforcing properties. Once involved, however,
      they believe that they derive a number of benefits that, for older adults, appear
      to offset declines in age-sensitive cognitive functions.

PMID- 23971426
TI  - Micronutrient fortification of food and its impact on woman and child health: a
      systematic review.
AB  - BACKGROUND: Vitamins and minerals are essential for growth and metabolism. The
      World Health Organization estimates that more than 2 billion people are deficient
      in key vitamins and minerals. Groups most vulnerable to these micronutrient
      deficiencies are pregnant and lactating women and young children, given their
      increased demands. Food fortification is one of the strategies that has been used
      safely and effectively to prevent vitamin and mineral deficiencies. METHODS: A
      comprehensive search was done to identify all available evidence for the impact
      of fortification interventions. Studies were included if food was fortified with
      a single, dual or multiple micronutrients and impact of fortification was
      analyzed on the health outcomes and relevant biochemical indicators of women and
      children. We performed a meta-analysis of outcomes using Review Manager Software
      version 5.1. RESULTS: Our systematic review identified 201 studies that we
      reviewed for outcomes of relevance. Fortification for children showed significant
      impacts on increasing serum micronutrient concentrations. Hematologic markers
      also improved, including hemoglobin concentrations, which showed a significant
      rise when food was fortified with vitamin A, iron and multiple micronutrients.
      Fortification with zinc had no significant adverse impact on hemoglobin levels.
      Multiple micronutrient fortification showed non-significant impacts on height for
      age, weight for age and weight for height Z-scores, although they showed positive
      trends. The results for fortification in women showed that calcium and vitamin D
      fortification had significant impacts in the post-menopausal age group. Iron
      fortification led to a significant increase in serum ferritin and hemoglobin
      levels in women of reproductive age and pregnant women. Folate fortification
      significantly reduced the incidence of congenital abnormalities like neural tube
      defects without increasing the incidence of twinning. The number of studies
      pooled for zinc and multiple micronutrients for women were few, though the
      evidence suggested benefit. There was a dearth of evidence for the impact of
      fortification strategies on morbidity and mortality outcomes in women and
      children. CONCLUSION: Fortification is potentially an effective strategy but
      evidence from the developing world is scarce. Programs need to assess the direct
      impact of fortification on morbidity and mortality.

PMID- 23971431
TI  - Exploring the predicted effect of social networking site use on perceived social
      capital and psychological well-being of Chinese international students in Japan.
AB  - This study investigated how social networking sites (SNSs) use by Chinese
      international students in Japan influenced their perceived social capital and
      psychological well-being. In addition, it examined how, as sojourners, Chinese
      international students' perceived acculturative stress varied. Data were
      collected from 142 Chinese international students. The results indicated that the
      intensity of SNS use was unable to predict individuals' perceived social capital
      and psychological well-being. The effect of SNS use varied according to the
      functions it serves. Specifically, SNS use for social and informational functions
      (SIF) increased individuals' levels of perceived bridging social capital and
      perceived life satisfaction, while SNS use for entertaining recreational
      functions (ERF) was unable to predict perceived social capital but increased
      individuals' levels of loneliness. It was also found that, in the intercultural
      environment, Chinese international students' levels of perceived acculturative
      stress were decreased by their perceived bonding social capital and increased by
      their perceived loneliness but had no relationship with their SNS use. Findings
      of the study suggest that individuals using SNSs to stay informed and connected
      will benefit with regard to their social network building and psychological well
      being.

PMID- 23971432
TI  - Internet addiction among elementary and middle school students in China: a
      nationally representative sample study.
AB  - The purpose of this study was to examine the prevalence of Internet addiction in
      a nationally representative sample of Chinese elementary and middle school
      students and to investigate Internet addiction among Internet users with
      different usages. 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. Only 54.2% of the students had accessed the
      Internet. According to the criteria of Young's Diagnostic Questionnaire (YDQ), an
      eight-item instrument, the prevalence of Internet addiction in the total sample
      was 6.3%, and among Internet users was 11.7%. Among the Internet users, males
      (14.8%) and rural students (12.1%) reported Internet addiction more than females
      (7.0%) and urban students (10.6%). The percentage of Internet addicts in
      elementary school students (11.5%) was not significantly lower than the
      percentage of middle school students (11.9%). There was no statistically
      significant difference between the four geographical regions (9.6%, 11.5%, 12.3%,
      11.1%) characterized by different levels of economy, health, education, and
      social environment. As the frequency of Internet use and time spent online per
      week increased, the percentage of Internet addicts increased. When considering
      the location and purpose of Internet use, the percentage of Internet addicts was
      highest in adolescents typically surfing in Internet cafes (18.1%) and playing
      Internet games (22.5%).

PMID- 23971433
TI  - The influence of computer literacy and computer anxiety on computer self
      efficacy: the moderating effect of gender.
AB  - Although researchers have published many studies on computer literacy and anxiety
      related to computer self-efficacy, there are two gaps in relevant literature.
      First, the effects of computer literacy and computer anxiety on computer self
      efficacy are considered separately, yet their interaction effect is neglected.
      Second, the role of individual gender characteristics in the relationships
      between computer literacy and anxiety on computer self-efficacy is far from
      clear. To address these two concerns, this study empirically investigates the
      interaction effect between computer literacy and computer anxiety, and the
      moderating role of gender. This study tests hypotheses using survey data from
      people who have experience using computers in Taiwan, and uses hierarchical
      regression to analyze the models. Results indicate that computer literacy can
      help form positive computer self-efficacy more effectively for males than for
      females, and computer anxiety can lead to more negative computer self-efficacy
      for females than for males. A three-way interaction also exists among computer
      literacy, computer anxiety, and gender. The results, research contributions, and
      limitations are discussed, and implications for future studies are suggested.

PMID- 23971434
TI  - Distribution and quantification of flavan-3-ols and procyanidins with low degree
      of polymerization in nuts, cereals, and legumes.
AB  - The monomeric flavan-3-ols catechin and epicatechin as well as procyanidins are
      of great interest due to their potential beneficial health effects observed in
      epidemiological studies. However, the occurrence and concentration of these
      compounds is not well-known due to the fact that reference compounds are not
      commercially available. In this study we determined the pattern and concentration
      of catechin, epicatechin, and different dimeric and trimeric procyanidins in 38
      food samples (nuts, cereals, legumes) using a reversed phase high-performance
      liquid chromatography electrospray ionization tandem mass spectrometry (RP-HPLC
      ESI-MS/MS) approach based on isolated authentic reference compounds. Of the
      analyzed food samples 21 were found to contain dimeric and trimeric procyanidins
      and their monomeric building units catechin and epicatechin. Mainly the monitored
      nut samples contained the analyzed procyanidins as well as catechin and
      epicatechin whereas only 3 cereals were identified as sources of the analyzed
      compounds. The concentration ranged from 148 MUg/100 g in macadamia nut to 55
      mg/100 g in pinto bean. Catechin and procyanidin B3 were found to be the most
      abundant analytes. The only A-type procyanidin that could be identified was
      procyanidin A2, which was found in peanut. The achieved data could be used for
      authenticity control and furthermore in combination with dietary studies to
      calculate the daily intake of monomeric flavan-3-ols and procyanidins. To our
      knowledge this is the first detailed study quantifying monomeric flavan-3-ols and
      dimeric and trimeric procyanidins in various nuts, cereals, and legumes. 

PMID- 23971435
TI  - An adult case of nephrotic syndrome presenting with pulmonary artery thrombosis:
      a case report.
AB  - INTRODUCTION: Pulmonary artery thrombosis is one of the most important
      complications in patients with nephrotic syndrome. It is well known among
      nephrologists, however, that this possibly lethal complication very rarely occurs
      before the diagnosis of nephrotic syndrome. CASE PRESENTATION: A 21-year-old
      Japanese woman who had no specific medical history consulted a primary care
      clinic. Although she had been aware of the edema of her lower extremities for 2
      weeks, her chief complaints were palpitations and chest pain, which had started
      the day before. An electrocardiogram and chest radiograph did not reveal any
      specific abnormalities. Because her etiology was not clear, she was referred to
      an emergency division in a hospital 2 days later. Although arterial blood gas
      analysis did not reveal hypoxemia, computed tomography revealed thrombi of the
      bilateral pulmonary arteries and left iliac vein. At this point, a laboratory
      examination confirmed the diagnosis of nephrotic syndrome. Subsequently, she was
      admitted, and anticoagulant therapy was initiated immediately. The next day, oral
      corticosteroid therapy was initiated, and an inferior vena cava filter was placed
      internally. Her proteinuria resolved after 3 weeks of treatment. The prompt and
      complete response to corticosteroid therapy suggested that minimal change disease
      was the etiology of the nephrotic syndrome and pulmonary artery thrombosis.
      CONCLUSIONS: An awareness regarding the complication of pulmonary artery
      thrombosis in nephrotic syndrome is important not only for nephrologists but for
      all clinicians. Contrast-enhanced computed tomography is crucial to detect
      pulmonary artery thrombosis.

PMID- 23971437
TI  - How do reviewers affect the final outcome? Comparison of the quality of peer
      review and relative acceptance rates of submitted manuscripts.
AB  - OBJECTIVE: The purpose of this study was to clarify how peer reviewers affect the
      relative rate of acceptance of manuscripts submitted to AJR: American Journal of
      Roentgenology. MATERIALS AND METHODS: Manuscript peer reviews for AJR are
      evaluated and rated by the journal editors on a scale from 1 (lowest) to 4
      (highest). These scores are subjective; they are not based on well-defined
      criteria and are not specifically defined other than as review quality. We
      obtained all peer review performance scores for the six main types of manuscripts
      received by AJR as initial submissions (as opposed to revisions) over 5 years and
      categorized the manuscripts into four groups based on the peer review performance
      score (not the manuscript rating). Statistical analysis included evaluation of
      differences in the relative acceptance rates of the manuscripts among the four
      groups. RESULTS: The relative acceptance rates of manuscripts in the lower review
      performance score groups (scores 1, 2, and 3) were significantly higher than
      those of the highest review score group (score 4) for Original Research (p=0.036,
      p<0.0001, p<0.0001) and Pictorial Essay (all p<0.0001, except for score 3)
      manuscripts. CONCLUSION: There was correlation between the quality of peer review
      performance and the relative acceptance rate of the manuscripts. It is important
      for AJR to retain highly rated reviewers to maintain its high publishing
      standards.

PMID- 23971438
TI  - Citation classics in radiology journals: the 100 top-cited articles, 1945-2012.
AB  - OBJECTIVE: The number of citations an article receives after its publication
      reflects its impact in the scientific community. The aim of this study was to
      identify and characterize the 100 top-cited articles published in radiology
      journals. MATERIALS AND METHODS: The top-cited articles published in 12 radiology
      journals were identified using the database of Science Citation Index Expanded
      (1945-2012). The 100 top-cited articles were selected and analyzed with regard to
      the number of citations, year of publication, publishing journal, authorship,
      institution and country of origin, type of article, radiologic subspecialty, main
      topic, and radiologic technique. RESULTS: The 100 top-cited articles were
      published in eight radiology journals, led by Radiology (n=67) and followed by
      the American Journal of Roentgenology (n=11). These articles were published
      between 1939 and 2006 with a mean of 664.3 citations per article (range, 371
      6931). Seventy-eight articles were published after 1979, 57 originated from the
      United States, and 69 were original articles. The most common subspecialties of
      study were interventional radiology (n=19), neuroradiology (n=15), and breast
      imaging (n=11). The main topics of articles were radiofrequency ablation of
      hepatic tumors (n=9), followed by receiver operating characteristic curves (n=6).
      CONCLUSION: Our study presents a detailed list and analysis of the 100 top-cited
      articles published in radiology journals, which provides insight into historical
      developments in the field of radiology.

PMID- 23971439
TI  - Section editor's notebook: focus on musculoskeletal imaging.

PMID- 23971440
TI  - Radiologic review of knee dislocation: from diagnosis to repair.
AB  - OBJECTIVE: This imaging-based article systematically reviews traumatic knee
      dislocations. After completion, the reader should be familiar with the
      definition, epidemiology, cause, and classification schemes associated with these
      injuries, as well as the importance of timely diagnostic imaging and an accurate,
      detailed description of findings, particularly as it relates to MRI
      interpretation. Finally, information our orthopedic surgical colleagues consider
      critical for the preoperative planning and reconstruction of the multiple
      ligament knee injury will be discussed. CONCLUSION: Although uncommon, traumatic
      knee dislocations are an important potentially limb-threatening injury, which if
      not emergently recognized and appropriately managed, can result in significant
      patient morbidity, joint dysfunction, chronic pain, and long-term disability. A
      radiologist familiar with the imaging appearance and potential neurovascular
      complications associated with these injuries can play an integral role in the
      multidisciplinary team that manages this increasingly recognized clinical entity.

PMID- 23971441
TI  - Ankle laxity: stress investigation under MRI control.
AB  - OBJECTIVE: The purpose of this study was to examine the advantages of MRI-guided
      ankle stress examinations in the detection of chronic ankle instability. SUBJECTS
      AND METHODS: An MRI-compatible stress device was developed and tested for MRI
      safety. Bilateral MRI stress examinations were performed on 50 volunteers with
      and without clinically evident subjective instability of the ankle joints (72
      subjective stable ankle joints in 37 subjects, 28 ankles in 15 subjects with
      chronic ankle instability). Both the inversion test and the anterior drawer test
      were performed under axial, coronal, 45 degrees  paraxial, and sagittal T2
      weighted fast spin-echo image control. MR images were assessed for talar tilt,
      subtalar tilt, anterior talus translation, anterior calcaneus translation, medial
      talocalcaneal translation, and the diameters of the lateral ankle ligaments
      (anterior talofibular ligament, calcaneofibular ligament, and posterior
      talofibular ligament). RESULTS: The MRI stress device was found suitable and safe
      for use in the MRI environment. The talocrural and subtalar joints could be
      assessed simultaneously. Significant differences between groups A and B (p<=0.05)
      were found in talar tilt, subtalar tilt, anterior talus translation, anterior
      calcaneus translation, medial talocalcaneal translation, and decrease in
      diameters of calcaneofibular and posterior talofibular ligaments. Also found were
      sex differences in talar tilt, subtalar tilt, anterior talus translation, and
      diameters of the anterior talofibular, calcaneofibular, and posterior talofibular
      ligaments. Significant relations were found between talar tilt and anterior talus
      translation, subtalar tilt and anterior calcaneus translation, subtalar tilt and
      medial talocalcaneal translation, and between anterior calcaneus translation and
      medial talocalcaneal translation in groups A and B. CONCLUSION: Stress
      examination under MRI control has advantages in the assessment of mechanical
      ankle instability. Additional diagnostic and clinically relevant information is
      obtained through direct imaging of the ligaments and assessment of additional
      parameters of ankle laxity (subtalar tilt, anterior calcaneus translation, medial
      talocalcaneal translation). The main advantages are objective imaging and
      measurement of abnormal looseness of the lower ankle joint and its direct
      simultaneous comparison with the upper ankle joint.

PMID- 23971442
TI  - Soft-tissue masses: optimal imaging protocol and reporting.
AB  - OBJECTIVE: Soft-tissue masses derive from a wide spectrum of tissues, and it may
      be difficult to differentiate nonneoplastic from neoplastic as well as benign
      from malignant lesions, to say nothing of making a single histologic diagnosis on
      the basis of imaging. The purpose of this article is to discuss optimal imaging
      protocols and reporting of soft-tissue masses. CONCLUSION: The radiologist should
      be prepared, if at all possible, to knowledgably examine the patient, optimize an
      imaging protocol, and differentiate among lesions. Specific features of an MRI
      examination must be discussed in each report to completely evaluate the mass and
      perform efficacious biopsy, staging, and eventual treatment of the lesion.
      Careful and systematic reporting of the examinations should avoid the devastating
      consequences of either overlooking a sarcoma or overtreating a benign lesion.

PMID- 23971443
TI  - Advanced imaging in gout.
AB  - OBJECTIVE: The purpose of this article is to describe the role of advanced
      imaging using ultrasound, CT, and MRI in the assessment and diagnosis of gout.
      CONCLUSION: Dual-energy CT can quantitatively identify monosodium urate crystal
      deposits with high sensitivity and specificity within joints, tendons, and
      periarticular soft tissues. There are several characteristic ultrasound imaging
      findings, which include visualization of echogenic monosodium urate crystal
      deposition, tophus, and adjacent erosions. MRI is sensitive in showing soft
      tissue and osseous abnormalities of gout, although the imaging findings are not
      specific. Gout commonly involves specific joints and anatomic structures, and
      knowledge of these sites and imaging appearances are clues to the correct
      diagnosis.

PMID- 23971444
TI  - Femoroacetabular impingement: fact, fiction, or fantasy?
AB  - OBJECTIVE: Proponents of femoroacetabular impingement (FAI) now claim that FAI is
      an important risk factor for hip osteoarthritis and argue that early, aggressive
      treatment is indicated to stave off long-term complications. The result is more
      young patients undergoing corrective surgery; does the literature support these
      claims or has hype trumped reality? This article critically reviews these
      assertions together with the current scientific evidence that defends (or
      refutes) them. CONCLUSION: Each reader will need to weigh the evidence carefully
      when interpreting images or planning management for patients with possible FAI.

PMID- 23971445
TI  - The CT appearance of lower respiratory infection due to parainfluenza virus in
      adults.
AB  - OBJECTIVE: We retrospectively reviewed the CT findings of lower respiratory tract
      infection (LRTI) due to parainfluenza virus (PIV) to determine the imaging
      features of PIV infection and to identify any differences compared with the CT
      appearances of LRTIs due to respiratory syncytial virus (RSV), adenovirus, and
      influenza virus. MATERIALS AND METHODS: The imaging features of LRTI from PIV
      over a 51-month period were retrospectively reviewed. The specific CT findings
      and overall pattern of infection in patients with LRTI due to PIV were recorded
      and were then compared with the CT appearances of RSV, adenovirus, and influenza
      LRTIs using data from a previous study. RESULTS: Twenty-four chest CT
      examinations of 24 patients with PIV infection were analyzed. Tree-in-bud
      opacities were the most common finding (13/24, 54%), and the airway-centric
      pattern of disease--characterized by combinations of bronchial wall thickening,
      tree-in-bud opacities, and peribronchiolar consolidation (bronchitis,
      bronchiolitis, and bronchopneumonia)--was the most common pattern (16/24, 67%).
      In comparison with previous data on RSV, adenovirus, and influenza virus, PIV
      showed tree-in-bud opacities and airway-centric patterns significantly more often
      than adenovirus or influenza virus. PIV and RSV showed similar CT findings and
      patterns of disease. CONCLUSION: Despite varying CT appearances of PIV LRTI, it
      most often shows airway-centric disease and is similar to the appearance of RSV
      infection, both of which are members of the Paramyxoviridae family of viruses.

PMID- 23971446
TI  - Malignant incidental extracardiac findings on cardiac CT: systematic review and
      meta-analysis.
AB  - OBJECTIVE: The objective of our study was to systematically review the evidence
      on incidental extracardiac findings on cardiac CT with a focus on previously
      unknown malignancies. MATERIALS AND METHODS: A systematic search was performed
      (PubMed, EMBASE, Cochrane databases) for studies reporting incidental
      extracardiac findings on cardiac CT. Among 1099 articles initially found, 15
      studies met the inclusion criteria. The references of those articles were hand
      searched and 14 additional studies were identified. After review of the full
      text, 10 articles were excluded. Nineteen studies including 15,877 patients (64%
      male) were analyzed. A three-level analysis was performed to determine the
      prevalence of patients with incidental extracardiac findings, the prevalence of
      patients with major incidental extracardiac findings, and the prevalence of
      patients with a proven cancer. Heterogeneity was explored for multiple variables.
      Pooled prevalence and 95% CI were calculated. RESULTS: The prevalence of both
      incidental extracardiac findings and major incidental extracardiac findings
      showed a high heterogeneity (I2>95%): The pooled prevalence was 44% (95% CI, 35
      54%) and 16% (95% CI, 14-20%), respectively. No significant explanatory variables
      were found for using or not using contrast material, the size of the FOV, and
      study design (I2>85%). The pooled cancer prevalence for 10 studies including 5082
      patients was 0.7% (95% CI, 0.5-1.0%), with an almost perfect homogeneity
      (I2<0.1%). Of 29 reported malignancies, 21 (72%) were lung cancers; three,
      thyroid cancers; two, breast cancers; two, liver cancers; and one, mediastinal
      lymphoma. CONCLUSION: Although the prevalence of reported incidental extracardiac
      finding at cardiac CT was highly variable, a homogeneous prevalence of previously
      unknown malignancies was reported across the studies, for a pooled estimate of
      0.7%; more than 70% of these previously unknown malignancies were lung cancers.
      Extracardiac findings on cardiac CT require careful evaluation and reporting.

PMID- 23971447
TI  - Intraductal papillary mucinous neoplasms with associated invasive carcinoma of
      the pancreas: imaging findings and diagnostic performance of MDCT for prediction
      of prognostic factors.
AB  - OBJECTIVE: The purpose of this study was to assess the diagnostic accuracy of
      MDCT for determining the prognostic factors, including the T category, lymph node
      metastasis, tumor size, and perineural invasion, in surgically proven intraductal
      papillary mucinous neoplasms (IPMNs) with an associated invasive carcinoma (IPMC)
      and to investigate the imaging findings. MATERIALS AND METHODS: Our study group
      consisted of 38 patients with surgically proven IPMC who underwent preoperative
      dynamic CT. Two radiologists retrospectively assessed the morphologic type of
      IPMN, size of the cyst, size of the main pancreatic duct, and presence or absence
      of mural nodules. The radiologists also assessed the T category, lymph node
      metastasis, and perineural invasion. They graded the perineural invasion using a
      3-point scale as follows: 1, normal; 2, streaky and strandlike structure in fat
      tissue as well as a fine, reticular pattern; and 3, irregular masses adjacent to
      the lesions. Statistical analyses were performed using receiver operating
      characteristic analysis, the McNemar test, and Fisher exact test. Kappa
      statistics were used to determine interobserver agreement. RESULTS: The
      morphologic types of IPMC included the main-duct type (n=11, 29%), combined type
      (n=18, 47%), and branch-duct type (n=9, 24%). The diagnostic accuracy for the T
      category was 73.7% (n=28) and 68.4% (n=26) and for the lymph node metastasis was
      68.4% (n=26) and 76.3% (n=29), respectively, for the two readers, with moderate
      interobserver agreement (kappa=0.636 and 0.708). The areas under the receiver
      operating characteristic curve for perineural invasion were 0.868 and 0.821. The
      sensitivity, specificity, and positive predictive value were 100%, 71.4%, 55.5%,
      and 90%, 71.4%, 52.9%, respectively. Interobserver agreement was moderate
      (kappa=0.659). The tumor size seen on CT was not statistically different from the
      tumor size determined on pathology (3.9+/-[SD] 2.7 cm vs 3.8+/-2.1 cm, p=0.582).
      The main duct size was 11.5+6.2 mm. Mural nodules were detected in 74% (n=28) of
      our study patients. CONCLUSION: CT might be useful for preoperatively evaluating
      the T category, lymph node metastasis, tumor size, and perineural invasion of
      IPMC. Main pancreatic duct dilatation and the presence of mural nodules are
      common findings of IPMC.

PMID- 23971448
TI  - MRCP in patient care: a prospective survey of gastroenterologists.
AB  - OBJECTIVE: MRCP is increasingly used to evaluate pancreaticobiliary disease, yet
      its effect on patient care is unknown. The purpose of this study was to measure
      the effect of MRCP on referring physicians' initial diagnoses, the physicians'
      confidence in their diagnoses, and the influence of MRCP results on clinical
      management. SUBJECTS AND METHODS: We prospectively surveyed gastroenterologists
      who referred patients for nonurgent MRCP for pancreaticobiliary evaluation.
      Before MRCP, gastroenterologists reported the working diagnosis, confidence level
      (high, moderate, low), and next step in clinical management if MRCP was
      unavailable. MRCP was performed with standard protocols, including secretin
      enhancement. After reviewing MRCP findings and without referring to their
      previous assessment, gastroenterologists reported a revised diagnosis, confidence
      level, and next step in clinical management. They then compared pre- and post
      MRCP management plans and rated the influence of MRCP on changing management from
      1 (none) to 5 (major). Diagnostic confidence and frequency of common diagnoses
      and recommendation for an invasive next-step procedure (e.g., ERCP) or endoscopic
      ultrasound were compared between pre- and post-MRCP assessments. RESULTS: Survey
      data were analyzed on 171 patients (123 women, 48 men; mean age, 50 [SD, 17]
      years; range, 19-88 years) undergoing MRCP for unexplained abdominal pain
      (42.9%), suspected pancreaticobiliary neoplasm (20%), recent acute (17.1%) or
      suspected chronic (14.9%) pancreatitis, and other indications (5.1%).
      Recommendations of ERCP and endoscopic ultrasound decreased after MRCP (from
      49.1% to 35.1%, p=0.03, and from 26.9% to 13.5%, p<=0.01). After MRCP, high
      confidence in diagnosis increased (from 72/171 to 100/171, p<0.01), as did
      recommendations for noninvasive therapy (from 18/171 to 56/171, p<0.01). A major
      or substantial change in clinical management was made in the care of 67 of 171
      patients (39.2%). CONCLUSION: Use of MRCP significantly changes
      gastroenterologists' treatment of patients with suspected pancreaticobiliary
      disease by increasing diagnostic confidence and reducing the frequency of
      invasive follow-up procedures.

PMID- 23971449
TI  - Evaluation of optimal scan delay for gadoxetate disodium-enhanced hepatic
      arterial phase MRI using MR fluoroscopic triggering and slow injection technique.
AB  - OBJECTIVE: The purpose of this article is to prospectively evaluate the optimal
      scan delay for gadoxetate disodium-enhanced hepatic arterial phase MRI of
      hypervascular hepatocellular carcinoma (HCC) using MR fluoroscopic triggering and
      a slow-injection technique. SUBJECTS AND METHODS: Sixty-three patients (37 men
      and 26 women; age range, 33-92 years; mean age, 68.2 years) underwent gadoxetate
      disodium-enhanced MRI; there were 33 hypervascular HCCs (size range, 8-57 mm;
      mean size, 19.8 mm) in 19 patients. The time from the start of contrast agent
      injection to its arrival in the abdominal aorta (time to arrival) and the time
      from contrast agent arrival to peak enhancement (time to peak) were determined
      using MR fluoroscopy using IV slow injection at 1 mL/s of contrast material and a
      saline chaser. All patients underwent four-phase whole-liver imaging with a 3D
      keyhole gradient-echo sequence during a single breath-hold immediately after
      confirmation of aortic peak enhancement. Delays from peak aortic enhancement to k
      space filling were 5-9, 10-14, 15-19, and 20-28 seconds, respectively, in the
      four phases. Time to arrival, time to peak, and HCC-to-liver contrast were
      evaluated. RESULTS: The time to arrival (range, 11-24 seconds; mean, 16.2
      seconds) and the time to peak (range, 3-10 seconds; mean, 6.8 seconds) showed
      considerable variation among patients. HCC-to-liver contrast peaked at the first
      phase in 58% of cases, at the second phase in 42% of cases, and at the third and
      fourth phases in 0% of cases. Mean HCC-to-liver contrast in the first and second
      phases was significantly higher than that in the third and fourth phases
      (p<0.01). CONCLUSION: Optimal scan delays for imaging hypervascular HCCs with
      gadoxetate disodium-enhanced hepatic arterial phase MRI was 7-12 seconds after
      the peak aortic enhancement using a slow-injection protocol.

PMID- 23971450
TI  - Automated patient-tailored screening of the liver for diffuse steatosis and iron
      overload using MRI.
AB  - OBJECTIVE: The purpose of this article is to validate an automated screening
      method for evaluation of hepatic steatosis or siderosis. MATERIALS AND METHODS:
      This was a two-part study, with retrospective and prospective portions. First,
      130 consecutive abdominal MRI examinations, including both the automated
      algorithm and reference standard fat and iron quantification, were
      retrospectively identified. The algorithm's performance was validated against the
      reference standard and was compared with the performance of three expert readers.
      Subsequently, 39 subjects undergoing liver MRI were prospectively identified and
      enrolled. These subjects were scanned with a protocol where quantification
      sequences were either performed or not performed on the basis of the
      recommendation of the algorithm. Total examination time in these subjects was
      compared with examination times in the 90 subjects from the retrospective cohort
      who had undergone a similar liver MRI protocol with complete quantification.
      RESULTS: The automated algorithm was accurate in determining the presence of
      deposition disease (93.1%), with no significant difference between its
      conclusions and those of any of the readers (p=0.48-1.0). Use of the algorithm
      resulted in a small but statistically significant time savings compared with
      performing quantification in all subjects (28 minutes 56 seconds vs 31 minutes 20
      seconds; p<0.05). CONCLUSION: Automated screening for hepatic steatosis and
      siderosis can be performed in real time during abdominal MRI examinations, can
      save total scan time compared with always performing quantification, and could
      serve as a gatekeeper for dedicated quantification sequences.

PMID- 23971451
TI  - MDCT and CT angiography evaluation of rectal bleeding: the role of volume
      visualization.
AB  - OBJECTIVE: This article reviews several different causes of rectal bleeding and
      the role of MDCT in diagnosis. CONCLUSION: Although colonoscopy remains the first
      line modality for the diagnosis of lower gastrointestinal tract bleeding,
      colonoscopy may not be possible for unstable patients, and moreover, even for
      patients who undergo colonoscopy, the examination may still fail to diagnose a
      cause for bleeding. MDCT with CT angiography and 3D mapping now offers a valuable
      option for diagnosis, not only for patients whose colonoscopy findings were
      negative, but also as a first-line screening modality for patients with active
      bleeding and hemodynamic instability. This article reviews the valuable role of
      MDCT in the diagnosis of multiple different causes of rectal bleeding, including
      rectal vascular malformations, rectal varices, ischemic colitis, stercoral
      colitis, inflammatory bowel disease, radiation proctopathy, infectious colitis,
      and rectal cancer.

PMID- 23971452
TI  - Comparison of segmental enhancement inversion on biphasic MDCT between small
      renal oncocytomas and chromophobe renal cell carcinomas.
AB  - OBJECTIVE: The purpose of this article is to assess the usefulness of segmental
      enhancement inversion on biphasic MDCT in differentiating small (<4 cm) renal
      oncocytomas from chromophobe renal cell carcinomas (CRCCs). MATERIALS AND
      METHODS: Eighty-two patients (40 men and 42 women) with a mean (+/-SD) age of
      54+/-12 years (range, 21-75 years) with 27 renal oncocytomas and 55 CRCCs
      diagnosed by surgery who underwent contrast-enhanced biphasic CT between January
      2000 and December 2011 were included. CT scans were interpreted by two
      radiologists who were blinded to the pathologic findings. The tumors were
      evaluated for size and segmental enhancement inversion. After independent
      evaluation, a consensus was reached by measuring the attenuation. Pathologic
      analysis determined the presence of fibrous septa, cystic change, hemorrhage, and
      necrosis. The Fisher exact test was used to evaluate the relationship between
      segmental enhancement inversion, tumor type, and specific pathologic changes.
      Interobserver concordance was evaluated with kappa statistics. RESULTS: There
      were no significant differences in size between renal oncocytomas and CRCCs
      (p=0.458). Segmental enhancement inversion was present in 23, 20, and 21 (25.6%)
      of the 82 tumors according to reader 1, reader 2, and the consensus,
      respectively. The agreement was almost perfect (kappa=0.843; p<0.001). Segmental
      enhancement inversion was more common in renal oncocytomas (63% [17/27]) than in
      CRCCs (7.3% [4/55]; p<0.001). There were no significant relationships between the
      four pathologic changes and tumor type or segmental enhancement inversion
      (p=0.351 and p=0.126, respectively). CONCLUSION: Our study findings suggest that
      segmental enhancement inversion on biphasic MDCT may be useful in differentiating
      small renal oncocytomas from CRCCs.

PMID- 23971453
TI  - Journal Club: Shoulder MRI utilization: relationship of physician MRI equipment
      ownership to negative study frequency.
AB  - OBJECTIVE: The purpose of this article is to determine whether ownership of MRI
      equipment by ordering physicians influences the frequency of negative shoulder
      MRI scans. MATERIALS AND METHODS: A retrospective review was performed of 1140
      consecutive shoulder MRI scans ordered by two separate referring physician groups
      serving the same geographic community. The first group (financially incentivized)
      owned the scanners used and received technical fees for their use. The second
      group (non-financially incentivized) did not own the scanners used and had no
      direct financial interest. All examinations were performed with identical
      protocols and were interpreted by a single radiologist group without financial
      interest in the imaging equipment used. The frequency of negative examinations
      and the number of abnormalities in each positive study was tabulated for each
      group. RESULTS: A total of 1140 shoulder MRI scans met inclusion criteria; 255
      were negative (142 for the financially incentivized group and 113 for the non
      financially incentivized group). There were 25.6% more negative scans in the
      financially incentivized group (p=0.047). There was no statistically significant
      difference in the average number of lesions per positive scan (1.67 for the
      financially incentivized group and 1.71 for the non-financially incentivized
      group; p=0.34). No statistically significant difference was found in the
      frequency of 19 of 20 examined lesions. CONCLUSION: Shoulder MRI examinations
      referred by physicians with a financial interest in the imaging equipment used
      were significantly more likely to be negative. Positive examinations exhibited no
      statistically significant difference in the number of lesions per scan or in the
      frequency of 19 of 20 lesion subtypes. This finding suggests a highly similar
      distribution and severity of disease among the two patient groups.

PMID- 23971454
TI  - Cognitive and system factors contributing to diagnostic errors in radiology.
AB  - OBJECTIVE: In this article, we describe some of the cognitive and system-based
      sources of detection and interpretation errors in diagnostic radiology and
      discuss potential approaches to help reduce misdiagnoses. CONCLUSION: Every
      radiologist worries about missing a diagnosis or giving a false-positive reading.
      The retrospective error rate among radiologic examinations is approximately 30%,
      with real-time errors in daily radiology practice averaging 3-5%. Nearly 75% of
      all medical malpractice claims against radiologists are related to diagnostic
      errors. As medical reimbursement trends downward, radiologists attempt to
      compensate by undertaking additional responsibilities to increase productivity.
      The increased workload, rising quality expectations, cognitive biases, and poor
      system factors all contribute to diagnostic errors in radiology. Diagnostic
      errors are underrecognized and underappreciated in radiology practice. This is
      due to the inability to obtain reliable national estimates of the impact, the
      difficulty in evaluating effectiveness of potential interventions, and the poor
      response to systemwide solutions. Most of our clinical work is executed through
      type 1 processes to minimize cost, anxiety, and delay; however, type 1 processes
      are also vulnerable to errors. Instead of trying to completely eliminate
      cognitive shortcuts that serve us well most of the time, becoming aware of common
      biases and using metacognitive strategies to mitigate the effects have the
      potential to create sustainable improvement in diagnostic errors.

PMID- 23971455
TI  - Consistency and efficiency of CT analysis of metastatic disease: semiautomated
      lesion management application within a PACS.
AB  - OBJECTIVE: The purpose of this study was to evaluate the success, consistency,
      and efficiency of a semiautomated lesion management application within a PACS in
      the analysis of metastatic lesions in serial CT examinations of cancer patients.
      MATERIALS AND METHODS: Two observers using baseline and follow-up CT data
      independently reviewed 93 target lesions (17 lung, five liver, 71 lymph node) in
      50 patients with either metastatic bladder or prostate cancer. The observers
      measured the longest axis (or short axis for lymph nodes) of each lesion and made
      Response Evaluation Criteria in Solid Tumors (RECIST) determinations using manual
      and lesion management application methods. The times required for examination
      review, RECIST calculations, and data input were recorded. The Wilcoxon signed
      rank test was used to assess time differences, and Bland-Altman analysis was used
      to assess interobserver agreement within the manual and lesion management
      application methods. Percentage success rates were also reported. RESULTS: With
      the lesion management application, most lung and liver lesions were
      semiautomatically segmented. Comparison of the lesion management application and
      manual methods for all lesions showed a median time saving of 45% for observer 1
      (p<0.05) and 28% for observer 2 (p=0.05) on follow-up scans versus 28% for
      observer 1 (p<0.05) and 9% for observer 2 (p=0.087) on baseline scans.
      Variability of measurements showed mean percentage change differences of only
      8.9% for the lesion management application versus 26.4% for manual measurements.
      CONCLUSION: With the lesion management application method, most lung and liver
      lesions were successfully segmented semiautomatically; the results were more
      consistent between observers; and assessment of tumor size was faster than with
      the manual method.

PMID- 23971456
TI  - The risk of cataract associated with repeated head and neck CT studies: a
      nationwide population-based study.
AB  - OBJECTIVE: Medical radiation-induced cataracts, especially those resulting from
      head and neck CT studies, are an issue of concern. The current study aimed to
      determine the risk of cataract associated with repeated radiation exposure from
      head and neck CT. MATERIALS AND METHODS: This study used information from a
      random sample of 2 million persons enrolled in the nationally representative
      Taiwan National Health Insurance Research Database. Exposed cases consisted of
      patients with head and neck tumor 10-50 years old who underwent at least one CT
      between 2000 and 2009. The nonexposed control group was composed of subjects who
      were never exposed to CT studies but who were matched by time of enrollment, age,
      sex, history of coronary artery disease, hypertension, and diabetes. RESULTS:
      There were 2776 patients in the exposed group and 27,761 matched subjects in the
      nonexposed group. The exposed group had higher overall incidence of cataracts
      (0.97% vs 0.72%; adjusted hazard ratio [HR], 1.76; 95% CI, 1.18-2.63). Further
      stratifying the number of CT studies in the exposed group into one or two, three
      or four, and five or more revealed that cataract incidence increased gradually
      with increasing frequency of CT studies (0.79%, 0.93%, and 1.45%, respectively)
      (p=0.001, adjusted for trend). Radiation exposure due to repeated head and neck
      CT studies was independently associated with an increased risk of developing
      cataracts when the cumulative CT exposure frequency involved more than four
      studies (adjusted HR, 2.12; 95% CI, 1.09-4.14). CONCLUSION: Repeated exposure to
      head and neck CT is significantly associated with increased risk of cataract.

PMID- 23971457
TI  - Central-variant posterior reversible encephalopathy syndrome: brainstem or basal
      ganglia involvement lacking cortical or subcortical cerebral edema.
AB  - OBJECTIVE: Although posterior reversible encephalopathy syndrome (PRES) typically
      involves cortical or subcortical edema of the cerebrum, only individual cases
      have been described of a variant involving the central brainstem and basal
      ganglia and lacking cortical and subcortical edema. We evaluated FLAIR and T2
      weighted images of 124 patients with confirmed PRES to determine the incidence of
      this uncommon variant, which we refer to as the "central variant"; to determine
      which structures are involved in this variant; and to determine the associated
      causes. CONCLUSION: We found that five of the 124 patients (4%) with PRES had MR
      findings consistent with the central variant-that is, either brainstem or basal
      ganglia involvement and a lack of cortical or subcortical edema of the cerebrum.
      The thalami were involved in all five PRES patients with MR findings consistent
      with the central variant, but there was variable involvement of the posterior
      limb of the internal capsule (4/5), cerebellum (3/5), and periventricular white
      matter (3/5); in each patient, there was improvement both clinically and on MRI.
      The causes of PRES in these five patients were hypertension (n=2), cyclosporine
      (n=2), and eclampsia (n=1). The incidence of the central variant may be
      increasing because of an improving awareness of the diverse imaging patterns of
      PRES.

PMID- 23971458
TI  - Can dual-time-point 18F-FDG PET/CT differentiate malignant salivary gland tumors
      from benign tumors?
AB  - OBJECTIVE: The purpose of this study is to evaluate the usefulness of dual-time
      point 18F-FDG PET/CT for discriminating between benign and malignant salivary
      gland tumors. MATERIALS AND METHODS: Dual-time-point FDG PET/CT images of 40
      salivary gland tumors (20 benign and 20 malignant) were evaluated
      retrospectively. The maximum standardized uptake values (SUVmax) in the early and
      delayed phases and the retention index of each tumor were calculated and compared
      between benign and malignant tumors by the Mann-Whitney U test. Receiver
      operating characteristic (ROC) analysis was used to determine the diagnostic
      accuracy for malignant salivary gland tumors. The correlation between the delayed
      SUVmax and retention index was analyzed by calculation of the Spearman
      correlation coefficient. RESULTS: There were no significant differences in the
      mean early phase SUVmax or mean delayed phase SUVmax between benign and malignant
      tumors. The mean (+/-SD) retention index of the malignant tumors was
      significantly higher than that of the benign tumors (20.1%+/-10.2% vs 8.5%+/
      12.3%; p=0.006). When the cutoff value of retention index (15.0%) was used, the
      sensitivity, specificity, and accuracy each was determined to be 75.0%. ROC
      analysis did not reveal a significant difference in the diagnostic accuracy
      between the delayed phase SUVmax and retention index (p=0.139). A significant
      correlation between the delayed phase SUVmax and retention index was observed for
      the benign salivary gland tumors (r=0.839; p<0.001). CONCLUSION: Dual-time-point
      FDG PET/CT is not useful for discriminating between benign and malignant salivary
      gland tumors, because benign tumors also show high FDG uptake, which increases in
      the delayed phase.

PMID- 23971459
TI  - Sonography-guided percutaneous liver biopsies in children.
AB  - OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of
      sonography-guided percutaneous core needle liver biopsy in infants and children.
      MATERIALS AND METHODS: We conducted a retrospective analysis of all patients who
      underwent sonography-guided percutaneous core needle liver biopsies over a 7.5
      year period by pediatric interventionalists at a single tertiary center. RESULTS:
      A total of 597 procedures were performed in 470 patients (270 male and 200
      female), with a mean age of 10.5 years (age range, 1 month-21 years). The main
      indications for biopsies were abnormal liver enzymes (n=129, 21.6%), grading and
      staging of chronic hepatitis B or C (n=105, 17.6%), evaluation of transplanted
      liver (n=111, 18.6%), iron overload (n=73, 12.2%), miscellaneous other diffuse
      parenchymal abnormalities (n=124, 20.7%), and focal hepatic lesions (n=55, 9.2%).
      The procedures were performed either under sedation (n=311, 52.1%) or general
      anesthesia (n=286, 47.9%). Diagnostic yield was obtained in 596 biopsies (99.8%)
      from an average of 2.4 cores in patients with diffuse disease (n=541, 90.6%) and
      6.5 cores in patients with focal disease (n=55, 9.2%). Ten patients (1.7%)
      experienced a major complication, including pneumothorax (n=1, 0.2%), abdominal
      wall pseudoaneurysm (n=1, 0.2%), and symptomatic bleeding (n=8, 1.3%). Five of
      these children required transfusion, two were only admitted for observation, and
      one required surgical evacuation. There were no procedure-related deaths. Minor
      complications (n=49, 8.2%) included a symptomatic subcapsular hematoma (n=35) and
      stable small hemoperitoneum (n=9). CONCLUSION: Sonography-guided percutaneous
      core liver biopsy is a safe and effective procedure in children that has a high
      diagnostic yield and very low complication rate.

PMID- 23971460
TI  - Comparison of conventional and simulated reduced-tube current MDCT for evaluation
      of suspected appendicitis in the pediatric population.
AB  - OBJECTIVE: The purpose of this study was to compare CT with conventional and
      simulated reduced-tube current in the evaluation for acute appendicitis in
      children. MATERIALS AND METHODS: Validated noise-addition (tube current
      reduction) software was used to create 50% and 75% tube current reductions in 60
      CT examinations performed for suspected appendicitis, resulting in 180 image
      sets. Three blinded pediatric radiologists scored the randomized studies for the
      following factors: presence of the normal appendix or appendicitis (5-point
      scale; 1=definitely absent and 5=definitely present), presence of alternate
      diagnoses, and overall image quality (1=nondiagnostic and 5=excellent). Truth was
      defined by the interpretation of the conventional examination. RESULTS: For
      conventional examinations, the total number of reviews (60 cases*3 readers=180)
      in which the normal appendix was identified was 120 of 180 (66.7%), compared with
      108 of 180 (60%) in the 50% (p=0.19) and 91 of 180 (50.6%) in the 75% (p=0.002)
      tube current-reduction groups. Appendicitis was identified in a total of 39 of
      180 (21.7%), 38 of 180 (21.1%), and 37 of 180 (20.6%) examinations, respectively
      (p>0.05). This translates to sensitivities of 97% and 95% for the 50% and 75%
      tube current-reduction groups, respectively. Alternate diagnoses were detected in
      14%, 16%, and 13% of scans, respectively. Compared with conventional-tube current
      examinations, reader confidence and assessment of image quality were
      significantly decreased for both tube current-reduction groups. CONCLUSION:
      Simulated tube current-reduction technology provides for systematic evaluation of
      diagnostic thresholds. Application of this technology in the setting of suspected
      appendicitis shows that tube current can be reduced by at least 50% without
      significantly affecting diagnostic quality, despite a decrease in reader
      confidence and assessment of image quality.

PMID- 23971461
TI  - Therapeutic effectiveness of diagnostic lymphangiography for refractory
      postoperative chylothorax and chylous ascites: correlation with radiologic
      findings and preceding medical treatment.
AB  - OBJECTIVE: The purpose of this study was to assess the therapeutic effect of
      lymphangiography for refractory postoperative chylothorax and chylous ascites and
      analyze the relation between the clinical outcomes and radiologic findings or
      response to the preceding medical treatment. MATERIALS AND METHODS: Between
      January 2004 and June 2012, 14 patients underwent lymphangiography. All patients
      had been unresponsive to at least two medical treatments for 3-62 days (median,
      13.5 days) before lymphangiography. Leaks were classified as major, minor, and
      undetectable on the basis of radiologic findings including CT and conventional
      radiography after lymphangiography. The clinical outcomes were correlated with
      the radiologic findings or the changes of the daily chylous output after the
      preceding medical treatments. RESULTS: The leaks were healed in nine of 14
      patients (64.3%) by 3-29 days (median, 8 days) after lymphangiography. Healing
      was achieved for two of seven major leaks, and all of the minor leaks (n=4) and
      undetectable leaks (n=3) after lymphangiography. The remaining five major leaks
      were not healed after a median follow-up of 15 days. The daily output decreased
      more than half after medical treatment in seven of the 14 patients, and the leak
      was healed in six of these patients (85.7%) by 5-18 days (median, 10 days).
      CONCLUSION: Lymphangiography might be useful for the treatment of refractory
      postoperative chylothorax and chylous ascites.

PMID- 23971462
TI  - Large-bore nitinol stents for malignant superior vena cava syndrome: factors
      influencing outcome.
AB  - OBJECTIVE: The purpose of this article is to retrospectively evaluate the
      technical and clinical outcomes of large-bore nitinol stents for treating
      malignant superior vena cava syndrome. In addition, we analyzed factors
      potentially influencing the outcome. MATERIALS AND METHODS: Over a 7-year period,
      78 consecutive patients presented with superior vena cava syndrome related to
      primary lung tumor (n=62) or malignant lymphadenopathies (n=16). The factors
      analyzed were Kishi score at admission, tumor type, and need for an additional
      balloon-expandable stent. RESULTS: Technical success was obtained in all but one
      patient (99%), who presented with a stent migration immediately after insertion.
      In 17 patients (22%), an additional balloon-expandable stent was needed for
      complete expansion of the nitinol stent. For patients with symptomatic malignant
      lymphadenopathies or primary lung tumor, overall survival rates were 50% (n=8)
      and 54% (n=34), respectively, at 6 months and 19% (n=3) and 34% (n=21),
      respectively, at 12 months (p=0.376). There was no difference in survival as a
      function of the Kishi score (p=0.80) or of the placement of an additional balloon
      expandable stent (p=0.35). Finally, reocclusion events were noted in patients
      both with (n=1) and without (n=7) a balloon-expandable stent. CONCLUSION: Large
      bore nitinol stents are highly effective for malignant superior vena cava
      syndrome. The survival rates of patients with caval vein stenosis due to either
      the primary tumor or secondary enlarged adenopathies were equal. An additional
      balloon-expandable stent was required in 22% of cases owing to incomplete
      expansion of the nitinol stent but was not associated with higher thrombosis
      rate.

PMID- 23971463
TI  - Role of C-arm CT for transcatheter arterial chemoembolization of hepatocellular
      carcinoma: diagnostic performance and predictive value for therapeutic response
      compared with gadoxetic acid-enhanced MRI.
AB  - OBJECTIVE: The objective of our study was to investigate the diagnostic
      performance of C-arm CT and its value to predict response of hepatocellular
      carcinoma (HCC) to trans-catheter arterial chemoembolization (TACE) compared with
      gadoxetic acid-enhanced MRI. MATERIALS AND METHODS: Sixty-eight patients with
      HCCs (n=167; 145>1 cm, 22<=1 cm) underwent both C-arm CT immediately before TACE
      and gadoxetic acid-enhanced MRI within 2 weeks before TACE. Two radiologists
      rated the possibility of HCC using a 5-point confidence scale focused on the
      degree of arterial enhancement and the shape of the lesion seen on C-arm CT. They
      also graded the possibility of HCC on MRI based on the signal intensities on T1-
      and T2-weighted images, arterial enhancement, and hypointensity on both the late
      phase and the hepatobiliary phase. We also measured the apparent diffusion
      coefficient value. The diagnostic accuracy was evaluated using the alternative
      free-response receiver operating characteristic curve method. A multivariate
      logistic regression analysis was performed between the good-response and
      nonresponse HCCs for TACE. RESULTS: The diagnostic accuracy of MRI was greater
      than that of C-arm CT (0.890 vs 0.681, respectively; p<0.001). However, in small
      HCCs (<=1 cm), C-arm CT showed a higher sensitivity than MRI (90.9% vs 70.5%,
      respectively; p=0.023) and a lower positive predictive value than MRI (40.8% vs
      57.4%, p=0.073). Well-defined strong arterial enhancement on C-arm CT (odds
      ratio=8.08, p=0.05) was statistically significant for predicting therapeutic
      response of HCC to TACE. CONCLUSION: C-arm CT showed greater sensitivity than
      gadoxetic acid-enhanced MRI in depicting small HCCs (<=1 cm). Furthermore, well
      defined strong arterial enhancement on C-arm CT can be used to predict
      therapeutic response of HCC to TACE.

PMID- 23971464
TI  - Patient age and tumor size determine the cancer yield of preoperative bilateral
      breast MRI in women with ductal carcinoma in situ.
AB  - OBJECTIVE: The objective of our study was to determine the cancer yield of
      preoperative breast MRI in women with newly diagnosed ductal carcinoma in situ
      (DCIS) and to identify subgroups of DCIS patients for whom MRI is more likely to
      identify additional cancers. MATERIALS AND METHODS: A database search for
      patients with DCIS who had undergone breast surgery between 2007 and 2011 was
      performed. A total of 308 women (median age, 49 years; range, 25-82 years) with
      DCIS underwent mammography, sonography, and a preoperative evaluation with MRI.
      The cancer yield and positive biopsy rate were determined. Patient age at
      diagnosis, menopausal status, family history of breast cancer, mammographic
      breast density, index cancer size, nuclear grade, and estrogen receptor (ER)
      status were examined, and a multivariate logistic regression analysis was
      performed. RESULTS: The cancer yield was 8% (24/308), and the positive biopsy
      rate was 53% (24/45). Of the 24 additional cancers, 14 (58%) represented
      multifocal disease, two (8%) represented multicentric disease, and eight (33%)
      represented contralateral cancer. In a multivariate analysis, age and index
      cancer size were factors significantly associated with additional MRI-detected
      cancers. Compared with women>=50 years, women<50 years had a 3.2-fold higher
      frequency of detection (95% CI, 1.2-8.9; p=0.02). Compared with women with DCIS
      lesions smaller than 2.5 cm, women with DCIS lesions 2.5 cm or larger showed a
      2.6-fold higher frequency of detection (95% CI, 1.1-6.3; p=0.04). CONCLUSION:
      Preoperative breast MRI can be considered in patients with DCIS who are <50 years
      old, have index cancers>=2.5 cm, or fulfill both criteria.

PMID- 23971465
TI  - Radiologist assessment of breast density by BI-RADS categories versus fully
      automated volumetric assessment.
AB  - OBJECTIVE: The objective of our study was to estimate mammographic breast density
      using a fully automated volumetric breast density measurement method in
      comparison with BI-RADS breast density categories determined by radiologists.
      MATERIALS AND METHODS: A total of 791 full-field digital mammography examinations
      with standard views were evaluated by three blinded radiologists as BI-RADS
      density categories 1-4. For fully automated volumetric analysis, volumetric
      breast density was calculated with fully automated software. The volume of
      fibroglandular tissue, the volume of the breast, and the volumetric percentage
      density were provided. RESULTS: The weighted overall kappa was 0.48 (moderate
      agreement) for the three radiologists' estimates of BI-RADS density. Pairwise
      comparisons of the radiologists' measurements of BI-RADS density revealed
      moderate to substantial agreement, with kappa values ranging from 0.51 to 0.64.
      There was a significant difference in mean volumetric breast density among the BI
      RADS density categories, and the mean volumetric breast density increased as the
      BI-RADS density category increased (p<0.001). A significant positive correlation
      was found between BI-RADS categories and fully automated volumetric breast
      density (rho=0.765, p<0.001). CONCLUSION: Our study showed good correlation of
      the fully automated volumetric method with radiologist-assigned BI-RADS density
      categories. Mammographic density assessment with the fully automated volumetric
      method may be used to assign BI-RADS density categories.

PMID- 23971467
TI  - Lacrimal gland masses.

PMID- 23971468
TI  - Nonneoplastic diseases of the small intestine: clinical, pathophysiologic, and
      imaging characteristics.

PMID- 23971469
TI  - Declining impact factor of radiologic journals: a matter for debate.
AB  - OBJECTIVE: As reported in the 2011 Journal Citation Reports, despite an increase
      of the impact factor (IF) for 54% of all journals, only 39% of imaging journals
      experienced an IF increase. Of the 41 imaging journals with an IF of higher than
      2.0, only 17 obtained a higher IF value in 2011 than in 2010 and the IF of most
      key international imaging journals decreased. How to manage and contrast this
      decline in IF is still a challenge for the radiologic community all over the
      world. CONCLUSION: Radiologic journals may try to increase their IF by soliciting
      important articles, such as meta-analyses, cost-effective analyses, and
      guidelines, that are frequently published in high-IF clinical journals, and
      encouraging nonradiologists to submit relevant radiologic-related clinical
      articles.

PMID- 23971470
TI  - Hip anatomic variants that may mimic abnormalities at MRI: labral variants.
AB  - OBJECTIVE: Normal anatomic variants of the acetabular labrum are observed on MR
      images and include labral variants, several sublabral sulci, and perilabral
      sulcus. Because variants can be misidentified as labral abnormalities such as
      labral tears, the radiologist needs to avoid the pitfall of mistaking variants as
      abnormalities. CONCLUSION: The hip has multiple anatomic variants that can mimic
      abnormalities at hip MRI. The labrum has several anatomic variants that can be
      confused with true labral tears.

PMID- 23971471
TI  - Hip anatomic variants that may mimic pathologic entities on MRI: nonlabral
      variants.
AB  - OBJECTIVE: The hip has several anatomic variants that may be mistaken for
      pathologic abnormalities. The radiologist needs to be able to distinguish these
      variants from true abnormalities. In this review, we present nonlabral variants
      of the hip that can be seen on MRI. CONCLUSION: The hip has multiple anatomic
      variants that may mimic disease on hip MRI. Like labral variants, nonlabral
      variants can be confused for true abnormalities.

PMID- 23971472
TI  - Traumatic shoulder injuries: a force mechanism analysis of complex injuries to
      the shoulder girdle and proximal humerus.
AB  - OBJECTIVE: Acute shoulder trauma can result in complex injuries to the bone and
      soft-tissue structures of the shoulder girdle with the associated risk of
      development of shoulder girdle instability. Destabilizing injuries to the
      shoulder girdle and fractures of the proximal humerus can occur in predictable
      patterns based on the injury mechanism. The objectives of this article are to
      illustrate the relevant anatomy of the shoulder, use 3D modeling and animation to
      aid in a mechanistic understanding of some of the most common injury patterns,
      discuss the most relevant radiologic findings that determine the ultimate
      treatment approach, and discuss an approach to imaging diagnosis with attention
      to the common treatment strategies. CONCLUSION: Understanding the force
      mechanisms responsible for the most common patterns of traumatic shoulder girdle
      injuries and proximal humeral fractures can improve detection of associated
      clinically significant secondary injuries, increase the effectiveness of injury
      classification, and ultimately direct appropriate and timely intervention.

PMID- 23971473
TI  - Acetabular fractures: anatomic and clinical considerations.
AB  - OBJECTIVE: Classifying acetabular fractures can be an intimidating topic.
      However, it is helpful to remember that there are only three basic types of
      acetabular fractures: column fractures, transverse fractures, and wall fractures.
      Within this framework, acetabular fractures are classified into two broad
      categories: elementary or associated fractures. We will review the osseous
      anatomy of the pelvis and provide systematic approaches for reviewing both
      radiographs and CT scans to effectively evaluate the acetabulum. CONCLUSION:
      Although acetabular fracture classification may seem intimidating, the
      descriptions and distinctions discussed and shown in this article hopefully make
      the topic simpler to understand. Approach the task by recalling that there are
      only three basic types of acetabular fractures: column fractures (coronally
      oriented on CT images), transverse fractures (sagittally oriented on CT images),
      and wall fractures (obliquely oriented on CT images). We have provided systematic
      approaches for reviewing both conventional radiographs and CT scans to
      effectively assess the acetabulum. The clinical implications of the different
      fracture patterns have also been reviewed because it is critically important to
      include pertinent information for our clinical colleagues to provide the most
      efficient and timely clinical care.

PMID- 23971474
TI  - Atypical hip impingement.
AB  - OBJECTIVE: This article summarizes how atypical forms of hip impingement can be
      assessed with radiographs, CT, and MRI. CONCLUSION: Subspine impingement,
      ischiofemoral impingement, and iliopsoas impingement are atypical forms of hip
      impingement and are less common than classic femoroacetabular impingement.
      Additional forms of atypical impingement, such as abnormal femoral antetorsion,
      abnormal pelvic and acetabular tilt, and extreme hip motion, can occur combined
      with classic femoroacetabular impingement or as separate entities.

PMID- 23971475
TI  - Customized knee arthroplasty and the role of preoperative imaging.
AB  - OBJECTIVE: The purpose of this article is to review advances in customized knee
      arthroplasty, highlighting advances in the use of preoperative imaging for
      component placement and design. CONCLUSION: Total knee arthroplasty is a highly
      successful surgical procedure. Although implant survivorship is generally
      excellent, failures do occur, and suboptimal component positioning is an
      important factor in implant failure. Surgical advances have focused on the use of
      advanced imaging and associated computer-assisted navigation to optimize
      component positioning.

PMID- 23971476
TI  - Technologically enhanced total knee replacement: is the juice worth the squeeze?
AB  - OBJECTIVE: The purpose of this article is to outline the limb alignment goals for
      knee replacement, current surgical technologies, and evidence-based medicine
      principles regarding technologically advanced total knee arthroplasty (TKA).
      Radiologists need an understanding of the pros and cons of technologically
      advanced TKA. CONCLUSION: At this time, the appropriate role for TKA has not been
      determined.

PMID- 23971477
TI  - Value of ultrasound before joint aspiration.
AB  - OBJECTIVE: The purpose of this article is to illustrate and discuss the value of
      ultra-sound screening before joint aspiration. CONCLUSION: Before joint
      aspiration, ultrasound assessment of the overlying and surrounding soft tissues
      requires little time and is relatively inexpensive. Bursal fluid collections,
      soft-tissue abscesses, and other fluid collections that would be undetected with
      fluoroscopy or blind aspiration can thus be identified. Ultrasound screening
      before joint aspiration can aid diagnosis and decrease the risk of iatrogenic
      complications.

PMID- 23971478
TI  - Relationships between airflow obstruction and quantitative CT measurements of
      emphysema, air trapping, and airways in subjects with and without chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: This study evaluates the relationships between quantitative CT (QCT)
      and spirometric measurements of disease severity in cigarette smokers with and
      without chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS:
      Inspiratory and expiratory CT scans of 4062 subjects in the Genetic Epidemiology
      of COPD (COPDGene) Study were evaluated. Measures examined included emphysema,
      defined as the percentage of low-attenuation areas<=-950 HU on inspiratory CT,
      which we refer to as "LAA-950I"; air trapping, defined as the percentage of low
      attenuation areas<=-856 HU on expiratory CT, which we refer to as "LAA-856E"; and
      the inner diameter, inner and outer areas, wall area, airway wall thickness, and
      square root of the wall area of a hypothetical airway of 10-mm internal perimeter
      of segmental and subsegmental airways. Correlations were determined between
      spirometry and several QCT measures using statistics software (SAS, version 9.2).
      RESULTS: QCT measurements of low-attenuation areas correlate strongly and
      significantly (p<0.0001) with spirometry. The correlation between LAA-856E and
      forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital
      capacity (FVC) (r=-0.77 and -0.84, respectively) is stronger than the correlation
      between LAA-950I and FEV1 and FEV1/FVC (r=-0.67 and r=-0.76). Inspiratory and
      expiratory volume changes decreased with increasing disease severity, as measured
      by the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) staging
      system (p<0.0001). When airway variables were included with low-attenuation area
      measures in a multiple regression model, the model accounted for a statistically
      greater proportion of variation in FEV1 and FEV1/FVC (R2=0.72 and 0.77,
      respectively). Airway measurements alone are less correlated with spirometric
      measures of FEV1 (r=0.15 to -0.44) and FEV1/FVC (r=0.19 to -0.34). CONCLUSION:
      QCT measurements are strongly associated with spirometric results showing
      impairment in smokers. LAA-856E strongly correlates with physiologic measurements
      of airway obstruction. Airway measurements can be used concurrently with QCT
      measures of low-attenuation areas to accurately predict lung function.

PMID- 23971479
TI  - Prostate cancer: comparison of dynamic contrast-enhanced MRI techniques for
      localization of peripheral zone tumor.
AB  - OBJECTIVE: The objective of this study was to compare the performance of
      different methodologies for interpretation of dynamic contrast-enhanced MRI (DCE
      MRI) in localization of peripheral zone prostate cancer. MATERIALS AND METHODS:
      Forty-three men (mean age, 59+/-8 years) with biopsy-proven prostate cancer who
      underwent prostate MRI including DCE-MRI before prostatectomy were included. Two
      observers independently reviewed DCE-MRI data using three methodologies:
      qualitative, in which kinetic curves of signal intensity versus time were
      generated for foci showing rapid enhancement on subtracted contrast-enhanced
      images; semiquantitative, in which a biexponential heuristic model was used to
      generate color-coded maps depicting maximum slope and washout of contrast
      enhancement; and quantitative, in which a Tofts model was used to generate color
      coded influx rate transfer constant (Ktrans) and efflux rate transfer constant
      (Kep) maps. Findings were stratified by whether suspicious foci showed evidence
      of washout with each method and compared with histopathologic results in each
      sextant. RESULTS: There was similar accuracy for the semiquantitative and
      quantitative models for both observers irrespective of requiring evidence of
      washout. For the more experienced observer, requiring washout resulted in lower
      sensitivity and higher specificity for the qualitative and semiquantitative
      models. Also for the more experienced observer, use of either a semiquantitative
      or quantitative model provided greater sensitivity compared with a qualitative
      model when requiring washout. There was no association between tumor detection
      and Gleason score for any DCE-MRI methodology for either reader. CONCLUSION: For
      the experienced reader, sensitivity for peripheral zone tumor was increased by
      use of either a semiquantitative or quantitative model compared with a
      qualitative model and decreased by requiring washout. We failed to identify a
      difference in performance between semiquantitative and quantitative models.

PMID- 23971480
TI  - Immediate postoperative sonography of renal transplants: vascular findings and
      outcomes.
AB  - OBJECTIVE: The purpose of this study was to determine the frequency and types of
      significant vascular findings on bedside sonography immediately after renal
      transplantation and which abnormalities would suggest a benefit from early
      surgical revision. MATERIALS AND METHODS: Five hundred seventy-five renal
      transplant sonograms obtained within 4 hours of surgery were retrospectively
      reviewed for major vascular abnormalities: lack of renal artery (RA) or renal
      vein (RV) flow, elevated peak systolic velocity (PSV)>300 cm/s, parvus tardus
      waveforms, and markedly decreased or no color parenchymal flow. Clinical outcomes
      of abnormal cases were reviewed, including reoperations and percutaneous
      interventions. RESULTS: Thirty-two (5.6%) patients underwent repeat surgery
      within the first week, 16 for nonvascular causes. Forty-seven (8.2%) patients had
      positive sonography findings. In 16 patients, sonography impacted the decision
      for reoperation, with 14 confirmed vascular diagnoses: compartment syndrome
      (n=7), RV thrombosis (n=3), RA thrombosis (n=1), RA and RV thromboses (n=2), and
      vascular steal (n=1). All were salvaged except the three RV thromboses. Two
      patients had no vascular abnormality at surgery. All 16 had markedly decreased
      color flow and varying abnormalities of PSV and waveforms. Outcomes of the
      remaining 31 cases were infarct (n=1), renal or iliac artery stenoses eventually
      requiring stents (n=4), and normalized (n=26). These 26 had elevated PSV with
      normal or near-normal color flow. Unpaired Student t tests showed no significant
      difference in PSV between patients requiring surgery or stents and those who
      normalized (p=0.34). CONCLUSION: Immediate postoperative sonography has a
      spectrum of vascular findings, of which markedly decreased color flow is most
      likely to benefit from immediate reoperation.

PMID- 23971481
TI  - Correlation of ultrasound findings with the Bethesda cytopathology classification
      for thyroid nodule fine-needle aspiration: a primer for radiologists.
AB  - OBJECTIVE: Ultrasound and ultrasound-guided fine-needle aspiration play a
      critical role in the evaluation of thyroid nodules. The Bethesda System for
      Reporting Thyroid Cytopathology (TBSRTC) was developed to facilitate
      communication among cytopathologists, radiologists, and referring physicians. The
      reporting scheme has rapidly become one of the most important contributions to
      thyroid nodule management. In this article, we review the significance of the
      TBSRTC categories and their implications in stratifying risk in the management of
      thyroid nodules. CONCLUSION: Knowledge of TBSRTC will allow the radiologist to
      better understand the criteria for thyroid nodule specimen adequacy, the
      components of risk stratification, and the standard terminology used for
      effective communication between patients and clinicians.

PMID- 23971483
TI  - Development of a novel breast MRI phantom for quality control.
AB  - OBJECTIVE: Many indications for breast MRI exist. MRI screening can identify
      preinvasive breast cancer in women at high risk and in that regard is superior to
      mammography and ultrasound. Quality control standards exist for mammography and
      breast ultra-sound screening with phantoms designed specifically for this
      purpose. Given the growing importance of breast MRI, we propose the development
      of a breast MRI phantom for quality control purposes. MATERIALS AND METHODS: A
      breast phantom with dual cavities containing water and fat was developed. A
      resolution plate inside the phantom contains various shapes ranging in size from
      1 to 20 mm. Twenty studies of the phantom were performed with a 1.5-T system.
      STIR, T1-weighted fat-suppressed, and T2-weighted sequences were completed.
      Relaxation times of water and fat, number of step shapes resolved on STIR and T2
      weighted images, number of circles resolved on T2-weighted images, and the
      diameter of a 20-mm circle on T1-weighted fat-suppressed images were recorded.
      RESULTS: On STIR images the TR of fat was 238.70+/-96.31 ms and of water was
      1231.92+/-399.14 ms. On T2-weighted images the TR of fat was 778.73+/-62.60 ms
      and of water was 1737.60+/-121.63 ms. On STIR images, steps 3 mm and larger were
      visualized in 95% of instances. On T2-weighted images steps 3 mm and larger were
      seen in all instances. Measurements of a 20-mm circle were 19+/-0.3 mm.
      CONCLUSION: The proposed breast MRI phantom can be used to obtain reproducible
      measurements and allows implementation of quality control measures for a modality
      that is being increasingly used.

PMID- 23971484
TI  - Medicolegal-malpractice and ethical issues in radiology: reporting the "missed"
      radiologic diagnosis.

PMID- 23971482
TI  - Perfusion MRI: the five most frequently asked clinical questions.
AB  - OBJECTIVE: This article addresses questions that radiologists frequently ask when
      planning, performing, processing, and interpreting MRI perfusion studies in CNS
      imaging. CONCLUSION: Perfusion MRI is a promising tool in assessing stroke, brain
      tumors, and neurodegenerative diseases. Most of the impediments that have limited
      the use of per-fusion MRI can be overcome to allow integration of these methods
      into modern neuroimaging protocols.

PMID- 23971485
TI  - Medicolegal-malpractice and ethical issues in radiology: displeased with defense
      lawyer.

PMID- 23971486
TI  - Differential diagnosis of upper lobe-predominant diseases of the lung.

PMID- 23971488
TI  - First report of Hepatozoon (Apicomplexa: Adeleorina) in caecilians, with
      description of a new species.
AB  - Hepatozoon spp. are identified for the first time in the amphibian order
      Gymnophiona, or caecilians, from the Seychelles island of Silhouette. Estimate of
      relationships derived from partial 18S rRNA gene sequences indicate these are not
      related to Hepatozoon spp. from frogs or to other Hepatozoon spp. from reptiles
      in the Seychelles. Assessment of mature gamonts from blood smears indicate that
      these can be recognized as a new species, Hepatozoon seychellensis n. sp.

PMID- 23971487
TI  - Gender differences in the relationship between diabetes-specific quality of life
      and depressive symptoms in middle-aged and older korean immigrants.
AB  - This study examined age and gender differences in the relationship between
      diabetes-specific quality of life (DQOL) and depressive symptoms among Korean
      immigrants with type 2 diabetes. In this cross-sectional study, 160 Korean
      immigrants ages 40 to 80 with diabetes were assessed for depressive symptoms,
      DQOL, and related demographic, clinical, and psychosocial factors. The
      relationship between DQOL and depressive symptoms was stronger for men than
      women. Whereas there were no main effects of age or gender in predicting
      depressive symptoms, there was a significant three-way interaction between
      gender, age (middle-aged or older), and DQOL on depressive symptoms, with older
      men demonstrating the strongest positive association between DQOL and depression.
      Age and gender differences should be considered for DQOL and depressive symptoms
      in Korean immigrants with diabetes. Efforts to address DQOL may likely have the
      greatest impact in decreasing depressive symptoms when targeted to older male
      Korean immigrants.

PMID- 23971489
TI  - The effects of facial adiposity on attractiveness and perceived leadership
      ability.
AB  - Facial attractiveness has a positive influence on electoral success both in
      experimental paradigms and in the real world. One parameter that influences
      facial attractiveness and social judgements is facial adiposity (a facial
      correlate to body mass index, BMI). Overweight people have high facial adiposity
      and are perceived to be less attractive and lower in leadership ability. Here, we
      used an interactive design in order to assess whether the most attractive level
      of facial adiposity is also perceived as most leader-like. We found that
      participants reduced facial adiposity more to maximize attractiveness than to
      maximize perceived leadership ability. These results indicate that facial
      appearance impacts leadership judgements beyond the effects of attractiveness. We
      suggest that the disparity between optimal facial adiposity in attractiveness and
      leadership judgements stems from social trends that have produced thin ideals for
      attractiveness, while leadership judgements are associated with perception of
      physical dominance.

PMID- 23971490
TI  - Differentiated brain activity in response to faces of "own" versus "unfamiliar"
      babies in primipara mothers: an electrophysiological study.
AB  - Experiences with one's own infant attune the parent nervous system to infant
      stimuli. To explore the effects of motherhood on brain activity patterns,
      electroencephalogram (EEG) was recorded while primipara mothers of 3- and 6-month
      olds viewed images of faces of their own child and an unfamiliar but appearance
      matched child. Mothers of 3- and 6-month-olds showed equivalent early-wave (N/P1
      "visual" and N170 "face-sensitive") responses to own and unfamiliar baby faces
      but differentiating late-wave (N/P600 "familiar/ novel") activity to own versus
      unfamiliar infant faces. Based on 3 months experience with their own infant's
      face, mothers' brain patterns give evidence of distinctive late-wave
      (recognition) sensitivity. 

PMID- 23971491
TI  - Neurophysiological correlates of auditory and language development: a mismatch
      negativity study.
AB  - During child development, physiological changes occur in the auditory cortex,
      which are reflected by differences in the electrophysiological signals. This
      study aimed to examine the age-related changes of the Mismatch Negativity
      component (MMN) in response to speech and non-speech stimuli in a cross-sectional
      design. Results revealed distinct patterns of activation according to stimulus
      type and age. Age-related differences for tone discrimination occurred earlier in
      children's development than did the discriminative process for speech sounds.
      Therefore, networks involved in speech processing are still immature in late
      childhood and may be more vulnerable to physiological changes. 

PMID- 23971492
TI  - Equiprobable and oddball paradigms: two approaches for documenting auditory
      discrimination.
AB  - The oddball paradigm is frequently used to study auditory discrimination.
      However, due to its lengthy recording sessions, an alternative design may be
      considered when time constraints are paramount. In the current study, auditory
      event-related potentials (ERPs) were obtained in 10 typical adults in response to
      two speech sound contrasts (/ba/-/ga/, /ba/-/pa/) presented using the oddball and
      equiprobable (equal trial counts for all conditions) paradigms. Sound
      discrimination was evident within the 100-300 msec post-stimulus window in both
      paradigms. Therefore, the equiprobable design can be a reasonable alternative to
      the oddball paradigm in situations when recording length threatens the quantity
      of available data. 

PMID- 23971493
TI  - Mathematical difficulties in nonverbal learning disability or co-morbid
      dyscalculia and dyslexia.
AB  - The main goal of the present study was to shed further light on the weaknesses of
      children with different profiles of mathematical difficulties, testing children
      with nonverbal learning disability (NLD), co-morbid dyscalculia and dyslexia
      (D&D), or typical development (TD). Sixteen children with NLD, 15 with D&D, and
      16 with TD completed tasks derived from Butterworth (2003 ) and divided into: a
      capacity subscale (i.e., a number-dots comparison task, a number comparison task,
      and a dots comparison task); and an achievement subscale (i.e., mental
      calculations and arithmetical fact retrieval). Children with NLD were impaired in
      the dots comparison task, children with D&D in the mental calculation and
      arithmetical facts. 

PMID- 23971494
TI  - Chitosan microparticles: influence of the gelation process on the release profile
      and oral bioavailability of albendazole, a class II compound.
AB  - Encapsulation of albendazole, a class II compound, into polymeric microparticles
      based on chitosan-sodium lauryl sulfate was investigated as a strategy to improve
      drug dissolution and oral bioavailability. The microparticles were prepared by
      spray drying technique and further characterized by means of X-ray powder
      diffractometry, infrared spectroscopy and scanning electron microscopy. The
      formation of a novel polymeric structure between chitosan and sodium lauryl
      sulfate, after the internal or external gelation process, was observed by
      infrared spectroscopy. The efficiency of encapsulation was found to be between 60
      and 85% depending on the internal or external gelation process. Almost
      spherically spray dried microparticles were observed using scanning electron
      microscopy. In vitro dissolution results indicated that the microparticles
      prepared by internal gelation released 8% of the drug within 30 min, while the
      microparticles prepared by external gelation released 67% within 30 min. It was
      observed that the AUC and Cmax values of ABZ from microparticles were greatly
      improved, in comparison with the non-encapsulated drug. In conclusion, the
      release properties and oral bioavailability of albendazole were greatly improved
      by using spraydried chitosan-sodium lauryl sulphate microparticles.

PMID- 23971495
TI  - Pluronic-poly (acrylic acid)-cysteine/Pluronic L121 mixed micelles improve the
      oral bioavailability of paclitaxel.
AB  - The aim of the study is to synthesize a thiolated Pluronic copolymer, Pluronic
      poly (acrylic acid)-cysteine copolymer, to construct a mixed micelle system with
      the Pluronic-poly (acrylic acid)-cysteine copolymer and Pluronic L121 (PL121) and
      to evaluate the potential of these mixed micelles as an oral drug delivery system
      for paclitaxel. Compared with Pluronic-poly (acrylic acid)-cysteine micelles,
      drug-loading capacity of Pluronic-poly (acrylic acid)-cysteine/PL121 mixed
      micelles was increased from 0.4 to 2.87%. In vitro release test indicated that
      Pluronic-poly (acrylic acid)-cysteine/PL121 mixed micelles exhibited a pH
      sensitivity. The permeability of drug-loaded micelles in the intestinal tract was
      studied with an in situ perfusion method in rats. The presence of verapamil and
      Pluronic both improved the intestinal permeability of paclitaxel, which further
      certified the inhibition effect of thiolated Pluronic on P-gp. In pharmacokinetic
      study, the area under the plasma concentration-time curve (AUC0->infinity) of
      paclitaxel-loaded mixed micelles was four times greater than that of the
      paclitaxel solution (p < 0.05). In general, Pluronic-poly (acrylic acid)
      cysteine/PL121 micelles were proven to be a potential oral drug delivery system
      for paclitaxel.

PMID- 23971497
TI  - Trametinib, a first-in-class oral MEK inhibitor mass balance study with limited
      enrollment of two male subjects with advanced cancers.
AB  - 1. This study assessed the mass balance, metabolism and disposition of
      [(14)C]trametinib, a first-in-class mitogen-activated extracellular signal
      related kinase (MEK) inhibitor, as an open-label, single solution dose (2 mg, 2.9
      MBq [79 uCi]) in two male subjects with advanced cancer. 2. Trametinib absorption
      was rapid. Excretion was primarily via feces (~81% of excreted dose); minor route
      was urinary (~19% of excreted dose). The primary metabolic elimination route was
      deacetylation alone or in combination with hydroxylation. Circulating drug
      related component profiles (composed of parent with metabolites) were similar to
      those found in elimination together with N-glucuronide of deacetylation product.
      Metabolite analysis was only possible from <50% of administered dose; therefore,
      percent of excreted dose (defined as fraction of percent of administered dose
      recovery over total dose recovered in excreta) was used to assess the relative
      importance of excretion and metabolite routes. The long elimination half-life
      (~10 days) favoring sustained targeted activity was important in permitting
      trametinib to be the first MEK inhibitor with clinical activity in late stage
      clinical studies. 3. This study exemplifies the challenges and adaptability
      needed to understand the metabolism and disposition of an anticancer agent, like
      trametinib, with both low exposure and a long elimination half-life.

PMID- 23971496
TI  - Mechanical stretch-induced activation of ROS/RNS signaling in striated muscle.
AB  - SIGNIFICANCE: Mechanical activation of reactive oxygen species (ROS) and reactive
      nitrogen species (RNS) occurs in striated muscle and affects Ca(2+) signaling and
      contractile function. ROS/RNS signaling is tightly controlled, spatially
      compartmentalized, and source specific. RECENT ADVANCES: Here, we review the
      evidence that within the contracting myocyte, the trans-membrane protein NADPH
      oxidase 2 (Nox2) is the primary source of ROS generated during contraction. We
      also review a newly characterized signaling cascade in cardiac and skeletal
      muscle in which the microtubule network acts as a mechanotransduction element
      that activates Nox2-dependent ROS generation during mechanical stretch, a pathway
      termed X-ROS signaling. CRITICAL ISSUES: In the heart, X-ROS acts locally and
      affects the sarcoplasmic reticulum (SR) Ca(2+) release channels (ryanodine
      receptors) and tunes Ca(2+) signaling during physiological behavior, but
      excessive X-ROS can promote Ca(2+)-dependent arrhythmias in pathology. In
      skeletal muscle, X-ROS sensitizes Ca(2+)-permeable sarcolemmal "transient
      receptor potential" channels, a pathway that is critical for sustaining SR load
      during repetitive contractions, but when in excess, it is maladaptive in diseases
      such as Duchenne Musclar dystrophy. FUTURE DIRECTIONS: New advances in ROS/RNS
      detection as well as molecular manipulation of signaling pathways will provide
      critical new mechanistic insights into the details of X-ROS signaling. These
      efforts will undoubtedly reveal new avenues for therapeutic intervention in the
      numerous diseases of striated muscle in which altered mechanoactivation of
      ROS/RNS production has been identified.

PMID- 23971498
TI  - Sitagliptin: results from clinical practice.

PMID- 23971500
TI  - A patient presenting with acute abdomen due to metastatic small bowel melanoma: a
      case report.
AB  - INTRODUCTION: Malignant tumors of the small bowel are rare. Melanoma of the small
      intestine is in most cases metastatic from a primary skin lesion. Perforation of
      small bowel melanoma is an extremely rare entity. To the best of our knowledge
      this is the fifth case published to date. CASE PRESENTATION: We report a rare
      case of acute abdomen due to perforated metastatic small bowel melanoma in a 38
      year-old Caucasian man. CONCLUSIONS: In the majority of cases small bowel
      melanoma represents metastasis from cutaneous sites. Although rare, the
      possibility of abdominal metastatic melanoma presenting with the clinical picture
      of acute abdomen must be always considered by the operating surgeon in patients
      with a history of primary cutaneous malignant lesion.

PMID- 23971501
TI  - Sunitinib as first-line neoadjuvant therapy in two patients with rectal stromal
      tumors.
AB  - In the treatment of rectal stromal tumors, which account for approximately 5% of
      gastrointestinal stromal tumors, molecular-targeted neoadjuvant therapy should be
      considered if the tumor is too large to achieve R0 grade resection or multiple
      visceral resection is required. Currently, imatinib is generally recommended as
      the first-line agent for such therapy. Although it has been reported that
      neoadjuvant therapy in patients experiencing imatinib resistance or intolerable
      adverse events can be successfully achieved by switching to sunitinib, first-line
      use of sunitinib for neoadjuvant therapy of gastrointestinal stromal tumors has
      not previously been reported. In this case report, first-line sunitinib
      neoadjuvant therapy of two patients who had very large rectal stromal tumors at
      sites close to the prostate and bladder produced good clinical outcomes. 

PMID- 23971502
TI  - Phosphoryl-related directing groups in rhodium(III) catalysis: a general strategy
      to diverse P-containing frameworks.
AB  - Herein, a rhodium(III)-catalyzed oxidative C-H activation of simple
      arylphosphonates and phosphonamides with subsequent coupling with alkenes
      (olefination), internal alkynes (hydroarylation and oxidative cyclization), or
      simple arenes to give access to diverse P-containing functional frameworks is
      reported. 

PMID- 23971503
TI  - Modeling the Temporal Dynamics of IT Neurons in Visual Search: A Mechanism for
      Top-Down Selective Attention.
AB  - We propose a neural model for object-oriented attention in which various visual
      stimuli (shapes, colors, letters, etc.) are represented by competing, mutually
      inhibitory, cell assemblies. The model's response to a sequence of cue and target
      stimuli mimics the neural responses in infero temporal (IT) visual cortex of
      monkeys performing a visual search task: enhanced response during the display of
      the stimulus, which decays but remains above a spontaneous rate after the cue
      disappears. When, subsequently, a display consisting of the target and several
      distractors is presented, the activity of all stimulus-driven cells is initially
      enhanced. After a short period of time, however, the activity of the cell
      assembly representing the cue stimulus is enhanced while the activity of the
      distractors decays because of mutual competition and a small top-down
      "expectational" input. The model fits the measured delayed activity in IT-cortex,
      recently reported by Chelazzi, Miller, Duncan, and Desimone (1993a), and we
      suggest that such a process, which is largely independent of the number of
      distractors, may be used by the visual system for selecting an expected target
      (appearing at an uncertain location) among distractors. 

PMID- 23971504
TI  - Effects of LTP on response selectivity of simulated cortical neurons.
AB  - We report here on specific ways in which synaptic long-term potentiation (LTP)
      affects the response selectivity of primary sensory cortical cells. LTP increases
      synaptic efficacy by incremental "steps," up to a "ceiling" at which additional
      bursts of afferent stimulation cause no further potentiation. Endogenous and
      exogenous agents have been shown to modulate these two paramenters of LTP,
      raising the question of the functional implications associated with the sizes of
      steps and ceiling. We provide an analytical treatment of the effects of these two
      physiological LTP parameters on the behavior of simulated olfactory (piriform)
      cortex target cells in response to a range of inputs. A target cell's receptive
      field, i.e., the set of input patterns to which the cell responds, is broadened
      with potentiation of the cell's synapses, and is broadened more when the LTP step
      size is smaller, and when the LTP ceiling is higher. Moreover, the effects of
      step size and ceiling interact, and their joint relationship to receptive field
      breadth is nonlinear. Values of step size and ceiling are identified that balance
      the tradeoff between learning rate and receptive field breadth for particular
      sensory recognition tasks, and these model values are compared to corresponding
      known and inferred physiological values. 

PMID- 23971505
TI  - The magnitude of the fixation offset effect with endogenously and exogenously
      controlled saccades.
AB  - Two experiments examined saccadic reaction time (RT) in response to visual
      targets as a function of fixation offset condition (no offset; target
      simultaneous with offset and 200-msec offset-target SOA) in prosaccade and
      antisaccade tasks. The second experiment also included a condition in which
      saccades were made in response to verbal commands presented auditorally. To
      ensure that observers were equally prepared in each condition, auditory warning
      tones preceded target onset on every trial. The RT reduction associated with
      fixation offset (FOE, or gap effect) was identical with visual targets in the
      prosaccade task and in response to verbal signals, strongly implicating motor,
      rather than sensory, mechanisms in the FOE. The FOE in the antisaccade task was
      significant, but it was also significantly smaller than in the other tasks. We
      speculate that the reduced FOE in the antisaccade task may be due to the
      requirement to inhibit the superior colliculus when the target directed saccadic
      programs are, by instruction, erroneous. 

PMID- 23971506
TI  - Dual Population Coding in the Neocortex: A Model of Interaction between
      Representation and Attention in the Visual Cortex.
AB  - The text describes a model that extends the population coding principles to any
      multidimensional attribute. The model distinguishes between the distribution of
      cell activity and the overall activity of a population. The distribution of cell
      activity is assumed to encode attribute information, while overall activity is
      assumed to reflect the significance or pertinence of the encoded attribute in the
      cerebral cortex, according to the dual coding principle. Three basic mechanisms
      of interaction between the representation of attribute and pertinence are defined
      and are applied to the motion (MT-MST) cortical pathway in the visual cortex.
      This framework determines three sources of pertinence that model cognitive
      processing, including preattentive processing, spatial-selective attention, and
      object-selective attention. The model accommodates most of the published
      psychophysical, neurophysiological, and neuroanatomical data and makes several
      testable predictions about the representations of attribute and enhanced effects
      in these areas. 

PMID- 23971507
TI  - Imagining real and unreal things: evidence of a dissociation in autism.
AB  - Current theories of visual imagery hold that the same neural processes govern
      both the representation of real objects and the representation of imagined (but
      real) objects. Here we test whether the representation of imagined (real) objects
      and the representation of imagined (but unreal) objects depend on the same or
      different neurocognitive processes. A likely clinical group for a dissociation
      between these two types of imagination are children with autism, since they show
      deficits in imaginative play, impoverished imagination is part of their
      diagnosis, but they can search for hidden objects. The present study explored
      imagination in autism using experimental methods. Experiment 1 investigated if
      children with autism could introduce changes to their representations of people
      and houses, using Karmiloff-Smith's (1989) technique of asking children to draw
      "impossible" people or houses. Results showed that children with autism were
      significantly worse than matched controls in their ability to introduce "unreal"
      changes to their representations of people and houses. Instead, they tended to
      draw real people or objects. Experiment 2 investigated whether the performance in
      Experiment 1 by children with autism was due to an inability to disengage from
      "real world" representations, as executive dysfunction theorists would argue. To
      do this, the experimenter instructed them on what to draw and how to draw it.
      Results showed that even when executive control passed to the experimenter in
      this way, the children with autism were still significantly impaired in their
      ability to draw imaginary but unreal things relative to the matched controls.
      Experiment 3 investigated whether the results from Experiments 1 and 2 arose
      because of a generativity deficit in autism, which might be the executive
      dysfunction theorists' alternative account. To test this, the same subjects were
      given a test of Verbal Fluency and a test of imagining multiple functions of a
      brick. Results showed that the children with autism were no worse than clinical
      controls in their ability to generate ideas about real objects, suggesting that a
      global generativity deficit cannot explain the previous findings. Rather, these
      results point to a specific impairment in the ability to imagine unreal objects.
      This is discussed in terms of its possible neural dissociability from other kinds
      of imagery, and in terms of its possible relationship to theory of mind. 

PMID- 23971508
TI  - An introduction to neural networks.

PMID- 23971509
TI  - The engine of reason, the seat of the soul: a philosophical journey into the
      brain.

PMID- 23971510
TI  - Dynamic patterns: the self-organization of brain and behavior.

PMID- 23971511
TI  - Structures and antioxidant and intestinal disaccharidase inhibitory activities of
      A-type proanthocyanidins from peanut skin.
AB  - Nine compounds including a new A-type proanthocyanidin trimer, epicatechin-(2beta
      >O->7,4beta->8)-[catechin-(6->4beta)]-epicatechin (8), and a known trimer,
      epicatechin-(4beta->8)-epicatechin-(2beta->O->7,4beta->8)-catechin (9), being
      reported for peanut skin for the first time, were isolated and purified. Their
      structures were determined by spectroscopic methods and by degradation reactions
      with L-cysteine in acidic conditions. The DPPH radical scavenging activity and
      the inhibitory activity on maltase and sucrase of the isolated compounds were
      investigated. All compounds showed strong DPPH scavenging activities (EC50 < 20
      MUg/mL). Compound 8 showed the strongest inhibitory activity on maltase with an
      IC50 value of 0.088 mg/mL, while compound 9 exhibited the strongest inhibition on
      sucrase with an IC50 value of 0.091 mg/mL.

PMID- 23971512
TI  - Tobacco cessation intervention for pregnant women in Argentina and Uruguay: study
      protocol.
AB  - BACKGROUND: Argentina and Uruguay are among the countries with the highest
      proportion of pregnant women who smoke. The implementation of an effective
      smoking cessation intervention would have a significant impact on the health of
      mothers and infants. The "5 A's" (Ask, Advise, Assess, Assist, Arrange) is a
      strategy consisting of a brief cessation counseling session of 5-15 minutes
      delivered by a trained provider. The "5 A's" is considered the standard of care
      worldwide; however, it is under used in Argentina and Uruguay. METHODS: We will
      conduct a two-arm, parallel cluster randomized controlled trial of an
      implementation intervention in 20 prenatal care settings in Argentina and
      Uruguay. Prenatal care settings will be randomly allocated to either an
      intervention or a control group after a baseline data collection period.
      Midwives' facilitators in the 10 intervention prenatal clinics (clusters) will be
      identified and trained to deliver the "5 A's" to pregnant women and will then
      disseminate and implement the program. The 10 clusters in the control group will
      continue with their standard in-service activities. The intervention will be
      tailored by formative research to be readily applicable to local prenatal care
      services at maternity hospitals and acceptable to local pregnant women and health
      providers. Our primary hypothesis is that the intervention is feasible in
      prenatal clinics in Argentina and Uruguay and will increase the frequency of
      women receiving tobacco use cessation counseling during pregnancy in the
      intervention clinics compared to the control clinics. Our secondary hypotheses
      are that the intervention will decrease the frequency of women who smoke by the
      end of pregnancy, and that the intervention will increase the attitudes and
      readiness of midwives towards providing counseling to women in the intervention
      clinics compared to the control clinics.

PMID- 23971513
TI  - Incidence, prevalence, and occurrence rate of infection among adults hospitalized
      after traumatic brain injury: study protocol for a systematic review and meta
      analysis.
AB  - BACKGROUND: Infection occurs commonly among patients hospitalized after traumatic
      brain injury (TBI) and has been associated with increased intensive care unit and
      hospital lengths of stay and an elevated risk of poor neurological outcome and
      mortality. However, as many relevant published studies to date have varied in the
      type and severity of TBI among included patients as well as in their design
      (randomized versus non-randomized), risk of bias, and setting (hospital ward
      versus intensive care unit), their reported estimates of infection occurrence
      vary considerably. Thus, the purpose of this systematic review and meta-analysis
      is to estimate the incidence, prevalence, and occurrence rate of infection among
      patients hospitalized after TBI. METHODS/DESIGN: We will search electronic
      bibliographic databases (MEDLINE, EMBASE, PubMed, Cumulative Index to Nursing and
      Allied Health Literature (CINAHL), Scopus, Web of Science, the Cochrane Central
      Register of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic
      Reviews) from their first available date as well as personal files, reference
      lists of included articles, and conference proceedings. Two investigators will
      independently screen titles and abstracts and select cohort studies, cross
      sectional studies, and randomized controlled trials involving adults hospitalized
      after TBI that reported estimates of cumulative incidence, incidence rate,
      prevalence, or occurrence rate of infection for inclusion in the systematic
      review. These investigators will also independently extract data and assess risk
      of bias. We will exclude studies with fewer than ten patients; experimental
      groups allocated to treatment with antibiotics, glucocorticoids,
      immunosuppressants, barbiturates, or hypothermia; and studies focused on
      military/combat-related TBI. Pooled estimates of cumulative incidence, incidence
      rate, prevalence, and occurrence rate will be calculated using random effects
      models. We will also calculate I2 and Cochran Q statistics to assess for inter
      study heterogeneity and conduct stratified analyses and univariate meta
      regression to determine the influence of pre-defined study-level covariates on
      our pooled estimates. DISCUSSION: This study will compile the world literature
      regarding the epidemiology of infection among adults hospitalized after TBI. A
      better understanding of the role of infection will be helpful in the development
      of guidelines for patient management. This protocol has been registered in the
      PROSPERO International Prospective Register of Systematic Reviews (ID:
      CRD42013005146).

PMID- 23971514
TI  - Development and evaluation of an intervention aiming to reduce fatigue in airline
      pilots: design of a randomised controlled trial.
AB  - BACKGROUND: A considerable percentage of flight crew reports to be fatigued
      regularly. This is partly caused by irregular and long working hours and the
      crossing of time zones. It has been shown that persistent fatigue can lead to
      health problems, impaired performance during work, and a decreased work-private
      life balance. It is hypothesized that an intervention consisting of tailored
      advice regarding exposure to daylight, optimising sleep, physical activity, and
      nutrition will lead to a reduction of fatigue in airline pilots compared to a
      control group, which receives a minimal intervention with standard available
      information. METHODS/DESIGN: The study population will consist of pilots of a
      large airline company. All pilots who posses a smartphone or tablet, and who are
      not on sick leave for more than four weeks at the moment of recruitment, will be
      eligible for participation.In a two-armed randomised controlled trial,
      participants will be allocated to an intervention group that will receive the
      tailored advice to optimise exposure to daylight, sleep, physical activity and
      nutrition, and a control group that will receive standard available information.
      The intervention will be applied using a smartphone application and a website,
      and will be tailored on flight- and participant-specific characteristics. The
      primary outcome of the study is perceived fatigue. Secondary outcomes are need
      for recovery, duration and quality of sleep, dietary and physical activity
      behaviours, work-private life balance, general health, and sickness absence. A
      process evaluation will be conducted as well. Outcomes will be measured at
      baseline and at three and six months after baseline. DISCUSSION: This paper
      describes the development of an intervention for airline pilots, consisting of
      tailored advice (on exposure to daylight and sleep-, physical activity, and
      nutrition) applied into a smartphone application. Further, the paper describes
      the design of the randomised controlled trial evaluating the effect of the
      intervention on fatigue, health and sickness absence. If proven effective, the
      intervention can be applied as a new and practical tool in fatigue management.
      Results are expected at the end of 2013. TRIAL REGISTRATION: Netherlands Trial
      Register: NTR2722.

PMID- 23971515
TI  - Comparative proteomics analysis of the rice roots colonized by Herbaspirillum
      seropedicae strain SmR1 reveals induction of the methionine recycling in the
      plant host.
AB  - Although the use of plant growth-promoting bacteria in agriculture is a reality,
      the molecular basis of plant-bacterial interaction is still poorly understood. We
      used a proteomic approach to study the mechanisms of interaction of
      Herbaspirillum seropedicae SmR1 with rice. Root proteins of rice seedlings
      inoculated or noninoculated with H. seropedicae were separated by 2-D
      electrophoresis. Differentially expressed proteins were identified by MALDI
      TOF/TOF and MASCOT program. Among the identified proteins of H. seropedicae, the
      dinitrogenase reductase NifH and glutamine synthetase GlnA, which participate in
      nitrogen fixation and ammonium assimilation, respectively, were the most
      abundant. The rice proteins up-regulated included the S-adenosylmethionine
      synthetase, methylthioribose kinase, and acireductone dioxygenase 1, all of which
      are involved in the methionine recycling. S-Adenosylmethionine synthetase
      catalyzes the synthesis of S-adenosylmethionine, an intermediate used in
      transmethylation reactions and in ethylene, polyamine, and phytosiderophore
      biosynthesis. RT-qPCR analysis also confirmed that the methionine recycling and
      phytosiderophore biosynthesis genes were up-regulated, while ACC oxidase mRNA
      level was down-regulated in rice roots colonized by bacteria. In agreement with
      these results, ethylene production was reduced approximately three-fold in rice
      roots colonized by H. seropedicae. The results suggest that H. seropedicae
      stimulates methionine recycling and phytosiderophore synthesis and diminishes
      ethylene synthesis in rice roots. 

PMID- 23971516
TI  - Lack of high-dose radiation mediated prostate cancer promotion and low-dose
      radiation adaptive response in the TRAMP mouse model.
AB  - Cancer of the prostate is a highly prevalent disease with a heterogeneous
      aetiology and prognosis. Current understanding of the biological mechanisms
      underlying the responses of prostate tissue to ionizing radiation exposure,
      including cancer induction, is surprisingly limited for both high- and low-dose
      exposures. As population exposure to radiation increases, largely through medical
      imaging, a better understanding of the response of the prostate to radiation
      exposure is required. Low-dose radiation-induced adaptive responses for increased
      cancer latency and decreased cancer frequency have been demonstrated in mouse
      models, largely for hematological cancers. This study examines the effects of
      high- and low-dose whole-body radiation exposure on prostate cancer development
      using an autochthonous mouse model of prostate cancer: TRansgenic Adenocarcinoma
      of the Mouse Prostate (TRAMP). TRAMP mice were exposed to single acute high (2
      Gy), low (50 mGy) and repeated low (5 * 50 mGy) doses of X rays to evaluate both
      the potential prostate cancer promoting effects of high-dose radiation and low
      dose adaptive response phenomena in this prostate cancer model. Prostate weights
      and histopathology were examined to evaluate gross changes in cancer development
      and, in mice exposed to a single 2 Gy dose, time to palpable tumor was examined.
      Proliferation (Ki-67), apoptosis, DNA damage (gamma-H2AX) and transgene
      expression (large T-antigen) were examined within TRAMP prostate sections.
      Neither high- nor low-dose radiation-induced effects on prostate cancer
      progression were observed for any of the endpoints studied. Lack of observable
      effects of high- or low-dose radiation exposure suggests that modulation of
      tumorigenesis in the TRAMP model is largely resistant to such exposures. However,
      further study is required to better assess the effects of radiation exposure
      using alternative prostate cancer models that incorporate normal prostate and in
      those that are not driven by SV40 large T antigen. 

PMID- 23971517
TI  - Improved method for evaluating the dead volume and protein-protein interactions
      by self-interaction chromatography.
AB  - Self-interaction chromatography (SIC) is a well-established method for studying
      protein-protein interactions. The second virial coefficient in SIC is evaluated
      directly from the measured retention coefficient for the protein using a column
      packed with resin on which the same protein has been immobilized on the pore
      surface. One of the challenges in determining the retention coefficient is the
      evaluation of the dead volume, which is the retention volume that would be
      measured for a noninteracting solute with the same effective size as the protein
      of interest. Previous studies of SIC have used a "dead column" packed with the
      same resin but without the immobilized protein to evaluate the dead volume, but
      this creates several experimental and theoretical challenges. We have developed a
      new approach using a dextran standard with effective size equal to that of the
      protein (as determined by size exclusion chromatography). The second virial
      coefficient was evaluated for a monoclonal antibody over a range of buffer
      conditions using this new approach. The data were in good agreement with
      independent measurements obtained by membrane osmometry under conditions
      dominated by repulsive interactions. The simplicity and accuracy of this method
      should facilitate the use of self-interaction chromatography for quantifying
      protein-protein interactions. 

PMID- 23971518
TI  - Friendly strategy to prepare encoded one bead-one compound cyclic peptide
      library.
AB  - One bead-one peptide libraries allow the screening of suitable ligands for any
      target protein. Short cyclic peptides are ideal ligands for affinity
      chromatography because of their high affinity and selectivity for the target
      protein and stability against proteases. We designed a library synthesis strategy
      to facilitate the identification of cyclic peptides by MS consisting of (a)
      sequential incorporation of a mixture of Fmoc-Ala-OH and Fmoc-Asp[2
      phenylisopropyl (OPp)]-OH (15:85) to Gly-oxymethylbenzamide-ChemMatrix (Gly-HMBA
      CM) resin, (b) synthesis of the combinatorial library on the resin by the divide
      couple-recombine method, (c) removal of OPp with 4% TFA, (d) peptide cyclization
      on solid phase through side-chain Asp and amino terminus, and (e) removal of side
      chain protecting groups with a 95% TFA cocktail. Peptides were cleaved from the
      beads with ammonia and the linear code was sequenced by MALDI-TOF MS/MS. The high
      capacity of ChemMatrix resin together with the sensitivity of MS allows code
      sequencing from a single bead. 

PMID- 23971519
TI  - An implementation model to increase the effectiveness of alcohol control
      policies.
AB  - PURPOSE: Public policies that reduce the availability of alcohol in communities
      can reduce consumption and related harms. In this article, we propose a practical
      model to guide alcohol policy implementation. APPROACH: The conceptual model is
      informed by a case study of three U.S. cities that adopted restrictions on high
      alcohol malt liquor sales. SETTING: The three cities included Seattle,
      Washington; Santa Ana, California; and Washington, D.C. PARTICIPANTS:
      Participants (n = 39) represented neighborhood groups, city officials, local
      police, Alcohol Beverage Control (board members and enforcement personnel),
      alcohol retailers, alcohol industry representatives, and advocacy and service
      organizations. METHOD: We conducted key informant interviews with participants in
      each city. We coded and analyzed the data by using a grounded theory approach.
      Findings were used to identify and illustrate model components. RESULTS:
      Implementation components include building public awareness and educating
      stakeholders, monitoring and enforcing compliance, evaluating process and
      outcomes, and institutionalizing the policy. The experiences of study cities
      illustrate the importance of these activities in maintaining policy
      effectiveness; for example, a lack of enforcement resources appeared to
      contribute to the erosion of compliance over time. CONCLUSION: The model
      addresses an important gap in alcohol policy research. It is intended to spur
      further research on the subject, provide a guide for policy practitioners, and
      ultimately improve the long-term effectiveness of alcohol control policies.

PMID- 23971520
TI  - Costs of a work-family intervention: evidence from the work, family, and health
      network.
AB  - PURPOSE: To estimate the cost to the workplace of implementing initiatives to
      reduce work-family conflict. DESIGN: Prospective cost analysis conducted
      alongside a group-randomized multisite controlled experimental study, using a
      microcosting approach. SETTING: An information technology firm. SUBJECTS:
      Employees (n = 1004) and managers (n = 141) randomized to the intervention arm.
      INTERVENTION: STAR (Start. Transform. Achieve. Results.) to enhance employees'
      control over their work time, increase supervisor support for employees to manage
      work and family responsibilities, and reorient the culture toward results.
      MEASURES: A taxonomy of activities related to customization, start-up, and
      implementation was developed. Resource use and unit costs were estimated for each
      activity, excluding research-related activities. ANALYSIS: Economic costing
      approach (accounting and opportunity costs). Sensitivity analyses on intervention
      costs. RESULTS: The total cost of STAR was $709,654, of which $389,717 was labor
      costs and $319,937 nonlabor costs (including $313,877 for intervention contract).
      The cost per employee participation in the intervention was $340 (95% confidence
      interval: $330-$351); $597 ($561-$634) for managers and $300 ($292-$308) for
      other employees (2011 prices). CONCLUSION: A detailed activity costing approach
      allows for more accurate cost estimates and identifies key drivers of cost. The
      key cost driver was employees' time spent on receiving the intervention. Ignoring
      this cost, which is usual in studies that cost workplace interventions, would
      seriously underestimate the cost of a workplace initiative.

PMID- 23971521
TI  - Relationships between transtheoretical model stages of change, decisional
      balance, self-efficacy, and physical activity level among Nigerian market
      vendors.
AB  - PURPOSE: This study explored decisional balance, self-efficacy, and physical
      activity (PA) level in relation to stages of change (SoC) for PA among Nigerian
      vendors. The study explored associations among decisional balance, self-efficacy,
      and PA level, and examined differences, by stage, in decisional balance, self
      efficacy, and PA level. DESIGN: Cross-sectional survey. SETTING: Outdoor markets
      located in Eke Amobi, Nkwo, and Okpuno Egbu in Nnewi, southeastern Nigeria.
      SUBJECTS: Participants were 499 market vendors (98 males and 401 females).
      MEASURES: Self-efficacy, perceived barrier and benefit, PA level, and SoC for PA.
      ANALYSIS: Spearman rank-order and partial correlations; analysis of variance by
      gender with Bonferroni post hoc adjustment. RESULTS: Self-efficacy (r = 0.69; p =
      0.000), perceived benefit (r = .12; p = .007), and perceived barrier (r = -.11; p
      = .017) for PA were related to the SoC. Adjusting for age, gender, and marital
      status, only self-efficacy (r = .48; p = .000) remained correlated with the SoC.
      In males, significant differences in perceived barrier (p = .003) and benefit (p
      = .003) lay between stages of contemplation and preparation and between stages of
      precontemplation and contemplation for self-efficacy (p = .006). In females,
      there were significance differences in self-efficacy across stages of
      precontemplation and contemplation (p = .000) and preparation and action (p =
      .007). CONCLUSION: When designing PA interventions, age, gender, and marital
      status should be considered in explaining the relationships between outcome
      constructs of transtheoretical model (TTM) and SoC in vendors. It is also
      important to note that the stages at which outcome constructs of TTM change
      during PA interventions vary in males and females.

PMID- 23971523
TI  - Network analysis of Bogota's Ciclovia Recreativa, a self-organized multisectorial
      community program to promote physical activity in a middle-income country.
AB  - PURPOSE: Conduct a social network analysis of the health and non-health related
      organizations that participate in Bogota's Ciclovia Recreativa (Ciclovia).
      DESIGN: Cross-sectional study. SETTING: Ciclovia is a multisectoral community
      based mass program in which streets are temporarily closed to motorized
      transport, allowing exclusive access to individuals for leisure activities and
      physical activity. SUBJECTS: Twenty-five organizations that participate in the
      Ciclovia. MEASURES: Seven variables were examined by using network analytic
      methods: relationship, link attributes (integration, contact, and importance),
      and node attributes (leadership, years in the program, and the sector of the
      organization). ANALYSIS: The network analytic methods were based on a visual
      descriptive analysis and an exponential random graph model. RESULTS: Analysis
      shows that the most central organizations in the network were outside of the
      Health sector and include Sports and Recreation, Government, and Security
      sectors. The organizations work in clusters formed by organizations of different
      sectors. Organization importance and structural predictors were positively
      related to integration, while the number of years working with Ciclovia was
      negatively associated with integration. CONCLUSION: Ciclovia is a network whose
      structure emerged as a self-organized complex system. Ciclovia of Bogota is an
      example of a program with public health potential formed by organizations of
      multiple sectors with Sports and Recreation as the most central.

PMID- 23971522
TI  - Seeking, delaying, and avoiding routine health care services: patient
      perspectives.
AB  - PURPOSE: To explore/identify patient perspectives regarding seeking, delaying,
      and avoiding health care services, particularly barriers and facilitators.
      DESIGN: Face-to-face interviews with health plan survey respondents. SETTING: An
      integrated health plan providing comprehensive care to 480,000 people in Oregon
      and Washington. PARTICIPANTS: Willing respondents randomly selected to maximize
      heterogeneity within the following strata: gender, health care utilization, and
      self-reported alcohol consumption (indicator of health practices). Participants
      were 75 men and 75 women (150 total), 21 to 64 years old, with >=12 months of
      health plan membership. METHOD: Participants were recruited by letter (52.5%
      agreed). Data collection stopped when planned interviews were completed;
      saturation (the point at which additional interviews were not producing novel
      information) was achieved for key study questions. Semi-structured interviews
      were recorded, transcribed, and coded. Reviews of codes related to care seeking
      and feelings/attitudes about providers produced common themes. RESULTS:
      Facilitators of care seeking included welcoming staff, collaborative
      relationships with providers, and education about the value of preventive care.
      Barriers included costs, time needed for appointments, and cumbersome processes.
      Some participants delayed procedures, some avoided care until absolutely
      necessary, others framed care as routinely necessary. CONCLUSION: Increasing
      comfort, improving appointment and visit-related processes, having positive
      patient-physician relationships, and enhancing communication and clinician
      provided education may facilitate appropriate use of preventive services. Further
      research is needed with larger, representative samples to evaluate findings.

PMID- 23971524
TI  - A pilot study of concurrent lead and cotinine screening for childhood tobacco
      smoke exposure: effect on parental smoking.
AB  - PURPOSE: To investigate whether a biomarker screening approach for tobacco smoke
      exposure (TSE) conducted concurrently with lead screening at well-child visits
      would increase parental smoking cessation and implementation of home smoking
      restrictions. DESIGN: Observational, quasi-experimental. SETTING: Pediatric
      clinic in Minneapolis, Minnesota. SUBJECTS: Eighty parents who smoked and their
      children presenting for well-child visits. INTERVENTION: Children in the
      intervention group had serum cotinine measured with lead screening. Laboratory
      results were sent to providers and parents and a counselor proactively contacted
      parents to offer an eight-session telephone intervention to help parents stop
      smoking. The comparison group, a historical control, received usual care.
      MEASURES: Parental smoking, engagement in tobacco treatment, and home and car
      smoking policies 8 weeks later. ANALYSIS: Mean/standard deviation for continuous
      data or frequency/percentage for categorical data. RESULTS: Eighty-four percent
      of eligible parents agreed to have their child tested for TSE along with lead
      testing. Measurable cotinine was identified in 93% of children. More parents in
      the intervention group received tobacco treatment than in the comparison group
      (74% vs. 0%) and more parents reported 7-day point-prevalent abstinence from
      smoking at 8 weeks (29% vs. 3%). CONCLUSION: These data demonstrate the
      feasibility of adding cotinine measurement to routine well-child lead screening
      to document TSE in small children. Data suggest providing this information to
      parents increases engagement in tobacco treatment and prompts smoking cessation.

PMID- 23971525
TI  - A microgeographic analysis of physical activity behavior within elementary school
      grounds.
AB  - PURPOSE: There is little scholarship on physical activity among children within
      outdoor spaces and work is needed to advance the design of these spaces from
      "best practices" towards evidence-based design. This project examined how
      playground feature density relates to children's physical activity. DESIGN: We
      used the System for Observing Play and Leisure Activity to observe children's
      physical activity. SETTING: We observed children during school recess on 24
      school grounds in the Denver metropolitan area of Colorado, in spring of 2010 and
      2011. SUBJECTS: A total of 31,069 observations were made from an estimated 9900
      children aged 5 to 12. These were aggregated and analyzed in 397 playground
      zones. MEASURES: We examined utilization, the number of children present in a
      particular activity zone during an observation, and the percentage of children
      engaged in moderate to vigorous physical activity as they relate to the density
      of constructed features on school playgrounds. ANALYSIS: Ordinary least-squares
      linear regression model assessed the relationship between playground feature
      density and the utilization and moderate to vigorous physical activity. RESULTS:
      Significant positive associations were observed between utilization and feature
      density among all children (beta = .20; p < .001) and a statistically significant
      but small association was observed between moderate to vigorous physical activity
      and feature density for girls (beta = .12; p = .013), but not for boys.
      CONCLUSION: This analysis contributes to evidence that design features of play
      spaces may influence children's behavior within school grounds.

PMID- 23971527
TI  - The long-term effect of perspective change on the emotional intensity of
      autobiographical memories.
AB  - Autobiographical memories can be recalled from either a field (first-person) or
      an observer (third-person) perspective. Previous studies have reported that field
      to-observer perspective change reduced the emotional intensity of recalled
      events. In the present study, we examined whether this effect has a long duration
      by employing follow-up measurements. The participants were asked to recall the
      same events repeatedly across three sessions (S1, S2, and S3): S2 was conducted
      about three days after S1, and S3 was conducted about four weeks after S2. The
      results showed a reduction in the emotional intensity of the recalled events when
      the perspective was changed from field to observer at S2. More importantly, this
      reduction in emotional intensity persisted until S3. These effects were not
      observed under observer-to-field perspective change at S2. These results suggest
      that observer perspective taking can cause plastic change in the autobiographical
      memory system. 

PMID- 23971526
TI  - Short-term effects of continuous subcutaneous insulin infusion therapy in
      perioperative patients with diabetes mellitus.
AB  - BACKGROUND: Hyperglycemia is common and hard to control in surgical patients with
      diabetes. We retrospectively investigated short-term effects of continuous
      subcutaneous insulin infusion (CSII) in perioperative patients with diabetes.
      PATIENTS AND METHODS: Perioperative patients with diabetes discharged between
      January 1, 2006 and January 1, 2012 were included. Glucose control and
      postoperative outcomes were compared between the patients using CSII or non-CSII
      insulin therapy. RESULTS: We identified 108 pairs of patients matched by
      propensity and surgical category who were using CSII therapy (CSII group) or non
      CSII insulin therapy (control group). The CSII group had significantly lower
      fasting glucose levels (on the first postoperative day, 9.06+/-3.09 mmol/L vs.
      11.05+/-4.19 mmol/L; P=0.003) and lower mean glucose levels (on the operation
      day, 9.93+/-2.65 mmol/L vs. 12.05+/-3.86 mmol/L; P=0.001). The CSII group also
      had a lower incidence of fever (on the first postoperative day, 30.4% vs. 53.2%;
      P=0.005). Furthermore, patients in the CSII group experienced significantly
      shorter postoperative intervals for suture removal (P=0.02) and hospital
      discharge (P=0.03). No significant difference in the total medical expenditure
      was observed between the two groups (P=0.47). We also made a comparison between
      the 30 pairs of patients who were using CSII or multiple daily insulin injection
      therapy but observed no significant difference between these two therapies in
      glucose control or postoperative outcomes. CONCLUSIONS: Compared with non-CSII
      insulin therapy, even short-term implementation of CSII can improve the
      postoperative control of glucose, reduce the incidence of postoperative fever,
      and shorten the time for suture removal and discharge in surgical patients with
      diabetes.

PMID- 23971528
TI  - Which immune cells matter? The immunopathogenesis of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS),
      which is believed to be immune-mediated. While CD4+ T cells have been the main
      suspects for years, there is ample evidence that other immune cells (including
      those of the innate immune system) play a contributing or regulating role in this
      disease. After a general introduction, this review focuses on different immune
      cell subsets implicated in MS pathogenesis and on current and future
      possibilities to target them for therapeutic use. 

PMID- 23971532
TI  - Erectile dysfunction with or without coexisting benign prostatic hyperplasia in
      the general US population: analysis of US National Health and Wellness Survey.
AB  - OBJECTIVE: Erectile dysfunction (ED) and benign prostatic hyperplasia (BPH)
      commonly affect older men. There is limited epidemiology information on
      coexisting ED and BPH. This study assessed self-reported prevalence of ED with or
      without a diagnosis of BPH (ED/DxBPH versus ED only) in US men. METHODS: Men >=40
      years old, who reported experiencing ED in the past 6 months with or without a
      diagnosis of BPH, were identified from the nationally representative 2011 US
      National Health and Wellness Survey (NHWS) - a cross-sectional, self-administered
      online survey. Unpaired t-tests were used to compare characteristics between ED
      only and ED/DxBPH populations. RESULTS: The prevalence of ED only and ED/DxBPH
      was 24.6% and 4.9% (mean ages of 60 and 68 years, respectively). About two-thirds
      of those with ED only and ED/DxBPH reported speaking to their physician about ED.
      About 23% of either group reported currently using ED medication and 11.7% of men
      with ED only were prescribed ED medication by a urologist, compared to 31.1% with
      ED/DxBPH. Approximately 51.7% of men with ED/DxBPH were taking BPH medication.
      Overall, 37.3% of men with ED only and 74.6% with ED/DxBPH reported moderate-to
      severe urinary symptoms on the American Urological Association-Symptom Index (AUA
      SI >=8). CONCLUSION: While self-reported ED is common, few men with ED in the US
      population report being diagnosed with BPH. The majority of ED only and ED/DxBPH
      men reported speaking to a physician about ED; however, few reported currently
      taking ED medication. A majority of men with ED/DxBPH reported an AUA-SI score
      >=8, but only half reported taking BPH medications. Thus, although men are
      experiencing erectile or urinary symptoms, many remain untreated. A limitation of
      this study is that symptoms and diagnosis were self-reported and may not reflect
      how these conditions are diagnosed in a healthcare setting; however, patient self
      report provides a unique perspective on the burden associated with these
      conditions.

PMID- 23971530
TI  - CD40 signaling to the rescue: A CD8 exhaustion perspective in chronic infectious
      diseases.
AB  - Chronic infectious diseases such as HIV, HBV, and HCV, among others, cause severe
      morbidity and mortality globally. Progressive decline in CD8 functionality,
      survival, and proliferative potential-a phenomenon referred to as CD8 exhaustion
      is believed to be responsible for poor pathogen control in chronic infectious
      diseases. While the role of negative inhibitory receptors such as PD-1 in
      augmenting CD8 exhaustion has been extensively studied, the role of positive
      costimulatory receptors remains poorly understood. In this review, we discuss how
      one such costimulatory pathway, CD40-CD40L, regulates CD8 dysfunction and rescue.
      While the significance of this pathway has been extensively investigated in
      models of autoimmunity, acute infectious diseases, and tumor models, the role
      played by CD40-CD40L in regulating CD8 exhaustion in chronic infectious diseases
      is just beginning to be understood. Considering that monotherapy with blocking
      antibodies targeting inhibitory PD-1-PD-L1 pathway is only partially effective at
      ameliorating CD8 exhaustion and that humanized CD40 agonist antibodies are
      currently available, a better understanding of the role of the CD40-CD40L pathway
      in chronic infectious diseases will pave the way for the development of more
      robust immunotherapeutic and prophylactic vaccination strategies. 

PMID- 23971531
TI  - Carbon monoxide confers protection in sepsis by enhancing beclin 1-dependent
      autophagy and phagocytosis.
AB  - AIMS: Sepsis, a systemic inflammatory response to infection, represents the
      leading cause of death in critically ill patients. However, the pathogenesis of
      sepsis remains incompletely understood. Carbon monoxide (CO), when administered
      at low physiologic doses, can modulate cell proliferation, apoptosis, and
      inflammation in pre-clinical tissue injury models, though its mechanism of action
      in sepsis remains unclear. RESULTS: CO (250 ppm) inhalation increased the
      survival of C57BL/6J mice injured by cecal ligation and puncture (CLP) through
      the induction of autophagy, the down-regulation of pro-inflammatory cytokines,
      and by decreasing the levels of bacteria in blood and vital organs, such as the
      lung and liver. Mice deficient in the autophagic protein, Beclin 1 (Becn1(+/-))
      were more susceptible to CLP-induced sepsis, and unresponsive to CO therapy,
      relative to their corresponding wild-type (Becn1(+/+)) littermate mice. In
      contrast, mice deficient in autophagic protein microtubule-associated protein-1
      light chain 3B (LC3B) (Map1lc3b(-/-)) and their corresponding wild-type
      (Map1lc3b(+/+)) mice showed no differences in survival or response to CO, during
      CLP-induced sepsis. CO enhanced bacterial phagocytosis in Becn1(+/+) but not
      Becn1(+/-) mice in vivo and in corresponding cultured macrophages. CO also
      enhanced Beclin 1-dependent induction of macrophage protein signaling lymphocyte
      activation molecule, a regulator of phagocytosis. INNOVATION: Our findings
      demonstrate a novel protective effect of CO in sepsis, dependent on autophagy
      protein Beclin 1, in a murine model of CLP-induced polymicrobial sepsis.
      CONCLUSION: CO increases the survival of mice injured by CLP through systemic
      enhancement of autophagy and phagocytosis. Taken together, we suggest that CO gas
      may represent a novel therapy for patients with sepsis.

PMID- 23971533
TI  - Using multisensory technology to create a therapeutic environment for people with
      dementia in an adult day center: a pilot study.
AB  - This quantitative pilot study examined the feasibility of using a multisensory
      environment (MSE) as a nonpharmacological intervention for people with behavioral
      and psychological symptoms of dementia (BPSD) within an adult day care center.
      Outcome measures were participant agitation, participant reaction to MSE, and
      caregiver satisfaction with MSE as a management strategy for older adults with
      BPSD. A within-subjects, repeated measures research design was used to obtain
      results from a total of 8 older adults with BPSD and 4 formal caregivers. Results
      indicated that the majority of participants enjoyed the MSE and improvements in
      some BPSD were observed after using the MSE. Reports from formal caregivers
      indicated that they believed the MSE was a useful nonpharmacological therapy for
      reducing anxiety and agitation among the day care participants who exhibited
      BPSD. Caregivers also suggested that this intervention should be incorporated
      into the design of the building and that a dedicated staff be assigned to
      facilitate the intervention for older adults each day.

PMID- 23971534
TI  - Nursing-sensitive outcome change scores for hospitalized older adults with heart
      failure: a preliminary descriptive study.
AB  - Nursing has a social mandate to ensure effective practice within its domain and
      to be accountable for the outcomes of nursing care. Using standardized nursing
      terminologies makes it possible to measure aspects of nursing care. The purpose
      of this study was to determine whether a significant difference in outcome
      ratings exists from admission to discharge for hospitalized older adults with
      heart failure (HF) using Nursing Outcomes Classification (NOC). A retrospective
      descriptive research design was used. Data were obtained from 268 inpatient
      records of patients discharged with HF during a 1-year period. All top 10 NOC
      outcomes demonstrated statistically significant improvement in outcome ratings
      from admission to discharge. Findings from this study provide insight on the
      possible contribution of nursing to outcomes of hospitalized older adults with
      HF. Validating and incorporating nursing-sensitive outcome measures in future
      prospective experimental research can contribute to the advancement of science
      regarding effective treatment of older adults hospitalized with HF, while
      highlighting the contribution of nursing care to outcomes.

PMID- 23971535
TI  - The complexity of older adults' social support networks.
AB  - The purpose of this study was to provide a detailed snapshot of the diversity of
      social support networks of 95 independent-living older adults (mean age = 76).
      Participants in the convenience sample were recruited from senior centers and a
      retirement community. Using the Arizona Social Support Interview Schedule and
      egocentric network analysis, participants' networks are described in terms of
      patterns, density, size of positive networks (available and utilized), size of
      negative networks (available and utilized), support need, and support
      satisfaction. Each participant and the identified members of his or her network
      were considered a complex adaptive system. Network boundary was 7 members;
      average network size was 6.22 members (SD = 1.50); network density was moderate
      (mean = 0.53, SD = 0.33); positive interaction networks were larger than negative
      networks; and overall, participants reported moderate support need (mean = 2.5,
      SD = 0.7) and high support satisfaction (mean = 5.9, SD = 1.0).

PMID- 23971536
TI  - Adjustment of traumatic femur shortening assisted by an intramedullar skeletal
      kinetic distractor: a case report.
AB  - INTRODUCTION: Distal comminuted femoral fractures with joint involvement are
      highly challenging for the surgeon. We present a potential therapeutic concept
      that aims especially at the treatment of posttraumatic leg length discrepancy.
      CASE PRESENTATION: This case report describes a polytraumatized 19-year-old
      German woman. Among other injuries she had a third grade open distal comminuted
      femoral fracture with a long distance metaphyseal osseous defect. As a primary
      care procedure an external fixation was applied at first. On day 13, an open
      reconstruction of her distal femur and the articular surface was performed by
      screw osteosynthesis, shortening and intramedullary nailing. Due to delayed
      osseous consolidation an autologous cancellous bone grafting was performed twice.
      In addition to the second cancellous bone graft an allogeneic cortical bone graft
      was implemented. A 6.5cm posttraumatic leg length shortening after osseous
      consolidation was the result. The entire leg length shortening was successfully
      treated 16 months after her accident with the help of an intramedullar skeletal
      kinetic distractor. CONCLUSIONS: With the help of the current case report of a
      patient with polytrauma and a third grade open distal comminuted femoral fracture
      with joint involvement and a long distance osseous defect, we present a potential
      therapeutic concept that aims especially at the treatment of posttraumatic leg
      length discrepancy.

PMID- 23971537
TI  - Studies on potential effects of fumaric acid on rumen microbial fermentation,
      methane production and microbial community.
AB  - The greenhouse gas methane (CH4) contributes substantially to global climate
      change. As a potential approach to decrease ruminal methanogenesis, the effects
      of different dosages of fumaric acid (FA) on ruminal microbial metabolism and on
      the microbial community (archaea, bacteria) were studied using a rumen simulation
      technique (RUSITEC). FA acts as alternative hydrogen acceptor diverting 2H from
      methanogenesis of archaea towards propionate formation of bacteria. Three
      identical trials were conducted with 12 fermentation vessels over a period of 14
      days. In each trial, four fermentation vessels were assigned to one of the three
      treatment groups differing in FA dosage: low fumaric acid (LFA), high fumaric
      acid (HFA) and without FA (control). FA was continuously infused with the buffer.
      Grass silage and concentrate served as substrate. FA led to decreases in pH and
      to higher production rates of total short chain fatty acids (SCFA) mediated by
      increases in propionate for LFA of 1.69 mmol d(-1) and in propionate and acetate
      production for HFA of 4.49 and 1.10 mmol d(-1), respectively. Concentrations of
      NH3-N, microbial crude protein synthesis, their efficiency, degradation of crude
      nutrients and detergent fibre fraction were unchanged. Total gas and CH4
      production were not affected by FA. Effects of FA on structure of microbial
      community by means of single strand conformation polymorphism (SSCP) analyses
      could not be detected. Given the observed increase in propionate production and
      the unaffected CH4 production it can be supposed that the availability of
      reduction equivalents like 2H was not limited by the addition of FA in this
      study. It has to be concluded from the present study that the application of FA
      is not an appropriate approach to decrease the ruminal CH4 production. 

PMID- 23971538
TI  - Domino Michael/Mannich/N-alkylation route to the tetrahydrocarbazole framework of
      aspidosperma alkaloids: concise total syntheses of (-)-aspidospermidine, (-)
      tabersonine, and (-)-vincadifformine.
AB  - We report a novel, asymmetric domino Michael/Mannich/N-alkylation sequence for
      the rapid assembly of the tetrahydrocarbazole framework of Aspidosperma
      alkaloids. This method was utilized in the concise total syntheses of classical
      targets (-)-aspidospermidine, (-)-tabersonine, and (-)-vincadifformine in 10 or
      11 steps. Additional key steps include ring-closing metathesis to prepare the D
      ring and Bosch-Rubiralta spirocyclization to prepare the C-ring. 

PMID- 23971539
TI  - Electromagnetic duality symmetry and helicity conservation for the macroscopic
      Maxwell's equations.
AB  - In this Letter, we show that the electromagnetic duality symmetry, broken in the
      microscopic Maxwell's equations by the presence of charges, can be restored for
      the macroscopic Maxwell's equations. The restoration of this symmetry is shown to
      be independent of the geometry of the problem. These results provide a tool for
      the study of light-matter interactions within the framework of symmetries and
      conservation laws. We illustrate its use by determining the helicity content of
      the natural modes of structures possessing spatial inversion symmetries and by
      elucidating the root causes for some surprising effects in the scattering off
      magnetic spheres. 

PMID- 23971540
TI  - Gap solitons in a spin-orbit-coupled Bose-Einstein condensate.
AB  - We report a diversity of stable gap solitons in a spin-orbit-coupled Bose
      Einstein condensate subject to a spatially periodic Zeeman field. It is shown
      that the solitons can be classified by the main physical symmetries they obey,
      i.e., symmetries with respect to parity (P), time (T), and internal degree of
      freedom, i.e., spin (C), inversions. The conventional gap and gap-stripe solitons
      are obtained in lattices with different parameters. It is shown that solitons of
      the same type but obeying different symmetries can exist in the same lattice at
      different spatial locations. PT and CPT symmetric solitons have antiferromagnetic
      structure and are characterized, respectively, by nonzero and zero total
      magnetizations. 

PMID- 23971541
TI  - Field fluctuations in a one-dimensional cavity with a mobile wall.
AB  - We consider a scalar field in a one-dimensional cavity with a mobile wall. The
      wall is assumed bounded by a harmonic potential and its mechanical degrees of
      freedom are treated quantum mechanically. The possible motion of the wall makes
      the cavity length variable, and yields a wall-field interaction and an effective
      interaction among the modes of the cavity. We consider the ground state of the
      coupled system and calculate the average number of virtual excitations of the
      cavity modes induced by the wall-field interaction, as well as the average value
      of the field energy density. We compare our results with analogous quantities for
      a cavity with fixed walls, and show a correction to the Casimir potential energy
      between the cavity walls. We also find a change of the field energy density in
      the cavity, particularly relevant in the proximity of the mobile wall, yielding a
      correction to the Casimir-Polder interaction with a polarizable body placed
      inside the cavity. Similarities and differences of our results with the dynamical
      Casimir effect are also discussed. 

PMID- 23971529
TI  - Dimethyl fumarate modulation of immune and antioxidant responses: application to
      HIV therapy.
AB  - The persistence of chronic immune activation and oxidative stress in human
      immunodeficiency virus (HIV)-infected, antiretroviral drug-treated individuals
      are major obstacles to fully preventing HIV disease progression. The immune
      modulator and antioxidant dimethyl fumarate (DMF) is effective in treating immune
      mediated diseases and it also has potential applications to limiting HIV disease
      progression. Among the relevant effects of DMF and its active metabolite
      monomethyl fumarate (MMF) are induction of a Th1 to Th2 lymphocyte shift,
      inhibition of pro-inflammatory cytokine signaling, inhibition of NF-kappaB
      nuclear translocation, inhibition of dendritic cell maturation, suppression of
      lymphocyte and endothelial cell adhesion molecule expression, and induction of
      the Nrf2-dependent antioxidant response element (ARE) and effector genes.
      Associated with these effects are reduced lymphocyte and monocyte infiltration
      into psoriatic skin lesions in humans and immune-mediated demyelinating brain
      lesions in rodents, which confirms potent systemic and central nervous system
      (CNS) effects. In addition, DMF and MMF limit HIV infection in macrophages in
      vitro, albeit by unknown mechanisms. Finally, DMF and MMF also suppress
      neurotoxin production from HIV-infected macrophages, which drives CNS
      neurodegeneration. Thus, DMF might protect against systemic and CNS complications
      in HIV infection through its effective suppression of immune activation,
      oxidative stress, HIV replication, and macrophage-associated neuronal injury. 

PMID- 23971542
TI  - Probing nonperturbative QED with optimally focused laser pulses.
AB  - We study nonperturbative pair production in intense, focused laser fields called
      e-dipole pulses. We address the conditions required, such as the quality of the
      vacuum, for reaching high intensities without initiating beam-depleting cascades,
      the number of pairs which can be created, and experimental detection of the
      created pairs. We find that e-dipole pulses offer an optimal method of
      investigating nonperturbative QED. 

PMID- 23971543
TI  - Coupling spin qubits via superconductors.
AB  - We show how superconductors can be used to couple, initialize, and read out
      spatially separated spin qubits. When two single-electron quantum dots are tunnel
      coupled to the same superconductor, the singlet component of the two-electron
      state partially leaks into the superconductor via crossed Andreev reflection.
      This induces a gate-controlled singlet-triplet splitting which, with an
      appropriate superconductor geometry, remains large for dot separations within the
      superconducting coherence length. Furthermore, we show that when two double-dot
      singlet-triplet qubits are tunnel coupled to a superconductor with finite
      charging energy, crossed Andreev reflection enables a strong two-qubit coupling
      over distances much larger than the coherence length. 

PMID- 23971544
TI  - Classification of multipartite entanglement of all finite dimensionality.
AB  - We provide a systematic classification of multiparticle entanglement in terms of
      equivalence classes of states under stochastic local operations and classical
      communication (SLOCC). We show that such a SLOCC equivalency class of states is
      characterized by ratios of homogenous polynomials that are invariant under local
      action of the special linear group. We then construct the complete set of all
      such SL-invariant polynomials (SLIPs). Our construction is based on Schur-Weyl
      duality and applies to any number of qudits in all (finite) dimensions. In
      addition, we provide an elegant formula for the dimension of the homogenous SLIPs
      space of a fixed degree as a function of the number of qudits. The expressions
      for the SLIPs involve in general many terms, but for the case of qubits we also
      provide much simpler expressions. 

PMID- 23971545
TI  - Monte carlo adaptive resolution simulation of multicomponent molecular liquids.
AB  - Complex soft matter systems can be efficiently studied with the help of adaptive
      resolution simulation methods, concurrently employing two levels of resolution in
      different regions of the simulation domain. The nonmatching properties of high-
      and low-resolution models, however, lead to thermodynamic imbalances between the
      system's subdomains. Such inhomogeneities can be healed by appropriate
      compensation forces, whose calculation requires nontrivial iterative procedures.
      In this work we employ the recently developed Hamiltonian adaptive resolution
      simulation method to perform Monte Carlo simulations of a binary mixture, and
      propose an efficient scheme, based on Kirkwood thermodynamic integration, to
      regulate the thermodynamic balance of multicomponent systems. 

PMID- 23971546
TI  - New limits on variation of the fine-structure constant using atomic dysprosium.
AB  - We report on the spectroscopy of radio-frequency transitions between nearly
      degenerate, opposite-parity excited states in atomic dysprosium (Dy). Theoretical
      calculations predict that these states are very sensitive to variation of the
      fine-structure constant alpha owing to large relativistic corrections of opposite
      sign for the opposite-parity levels. The near degeneracy reduces the relative
      precision necessary to place constraints on variation of alpha, competitive with
      results obtained from the best atomic clocks in the world. Additionally, the
      existence of several abundant isotopes of Dy allows isotopic comparisons that
      suppress common-mode systematic errors. The frequencies of the 754-MHz transition
      in 164Dy and 235-MHz transition in 162Dy are measured over the span of two years.
      The linear variation of alpha is alpha./alpha=(-5.8+/-6.9([1sigma]))*10(-17)  yr(
      1), consistent with zero. The same data are used to constrain the dimensionless
      parameter kalpha characterizing a possible coupling of alpha to a changing
      gravitational potential. We find that kalpha=(-5.5+/-5.2([1sigma]))*10(-7),
      essentially consistent with zero and the best constraint to date.

PMID- 23971547
TI  - Adiabatic quantum motors.
AB  - When parameters are varied periodically, charge can be pumped through a
      mesoscopic conductor without applied bias. Here, we consider the inverse effect
      in which a transport current drives a periodic variation of an adiabatic degree
      of freedom. This provides a general operating principle for adiabatic quantum
      motors which we discuss here in general terms. We relate the work performed per
      cycle on the motor degree of freedom to characteristics of the underlying quantum
      pump and discuss the motors' efficiency. Quantum motors based on chaotic quantum
      dots operate solely due to quantum interference, and motors based on Thouless
      pumps have ideal efficiency. 

PMID- 23971548
TI  - Determination of the Boltzmann constant by means of precision measurements of
      H2(18)O line shapes at 1.39  MUm.
AB  - We report on a new implementation of Doppler broadening thermometry based on
      precision absorption spectroscopy by means of a pair of offset-frequency locked
      extended-cavity diode lasers at 1.39  MUm. The method consists in the highly
      accurate observation of the shape of the 4(4,1)->4(4,0) line of the H2(18)O
      nu1+nu3 band, in a water vapor sample at thermodynamic equilibrium. A
      sophisticated and extremely refined spectral analysis procedure is adopted for
      the retrieval of the Doppler width as a function of the gas pressure, taking into
      account the Dicke narrowing effect, the speed dependence of relaxation rates, and
      the physical correlation between velocity-changing and dephasing collisions. A
      spectroscopic determination of the Boltzmann constant with a combined (type A and
      type B) uncertainty of 24 parts over 10(6) is reported. This is the best result
      obtained so far by means of an optical method. Our determination is in agreement
      with the recommended CODATA value.

PMID- 23971549
TI  - Establishing a relation between the mass and the spin of stellar-mass black
      holes.
AB  - Stellar mass black holes (SMBHs), forming by the core collapse of very massive,
      rapidly rotating stars, are expected to exhibit a high density accretion disk
      around them developed from the spinning mantle of the collapsing star. A wide
      class of such disks, due to their high density and temperature, are effective
      emitters of neutrinos and hence called neutrino cooled disks. Tracking the
      physics relating the observed (neutrino) luminosity to the mass, spin of black
      holes (BHs) and the accretion rate (M) of such disks, here we establish a
      correlation between the spin and mass of SMBHs at their formation stage. Our work
      shows that spinning BHs are more massive than nonspinning BHs for a given M.
      However, slowly spinning BHs can turn out to be more massive than spinning BHs if
      M at their formation stage was higher compared to faster spinning BHs.

PMID- 23971550
TI  - First results from the CARIBU facility: mass measurements on the r-process path.
AB  - The Canadian Penning Trap mass spectrometer has made mass measurements of 33
      neutron-rich nuclides provided by the new Californium Rare Isotope Breeder
      Upgrade facility at Argonne National Laboratory. The studied region includes the
      132Sn double shell closure and ranges in Z from In to Cs, with Sn isotopes
      measured out to A=135, and the typical measurement precision is at the 100 ppb
      level or better. The region encompasses a possible major waiting point of the
      astrophysical r process, and the impact of the masses on the r process is shown
      through a series of simulations. These first-ever simulations with direct mass
      information on this waiting point show significant increases in waiting time at
      Sn and Sb in comparison with commonly used mass models, demonstrating the
      inadequacy of existing models for accurate r-process calculations.

PMID- 23971551
TI  - Extending the range of the inductionless magnetorotational instability.
AB  - The magnetorotational instability (MRI) can destabilize hydrodynamically stable
      rotational flows, thereby allowing angular momentum transport in accretion disks.
      A notorious problem for the MRI is its questionable applicability in regions with
      low magnetic Reynolds number. Using the WKB method, we extend the range of
      applicability of the MRI by showing that the inductionless versions of the MRI,
      such as the helical MRI and the azimuthal MRI, can easily destabilize Keplerian
      profiles ?r(-3/2) if the radial profile of the azimuthal magnetic field is only
      slightly modified from the current-free profile ?r(-1). This way we further show
      how the formerly known lower Liu limit of the critical Rossby number Ro~-0.828
      connects naturally with the upper Liu limit Ro~+4.828.

PMID- 23971552
TI  - Solution of the alpha-potential mystery in the gamma process and its impact on
      the Nd/Sm ratio in meteorites.
AB  - The 146Sm/144Sm ratio in the early solar system has been constrained by Nd/Sm
      isotope ratios in meteoritic material. Predictions of 146Sm and 144Sm production
      in the gamma process in massive stars are at odds with these constraints, and
      this is partly due to deficiencies in the prediction of the reaction rates
      involved. The production ratio depends almost exclusively on the
      (gamma,n)/(gamma,alpha) branching at 148Gd. A measurement of
      144Sm(alpha,gamma)148Gd at low energy had discovered considerable discrepancies
      between cross-section predictions and the data. Although this reaction cross
      section mainly depends on the optical alpha+nucleus potential, no global optical
      potential has yet been found that can consistently describe the results of this
      and similar alpha-induced reactions at the low energies encountered in
      astrophysical environments. The untypically large deviation in 144Sm(alpha,gamma)
      and the unusual energy dependence can be explained, however, by low-energy
      Coulomb excitation, which is competing with compound nucleus formation at very
      low energies. Considering this additional reaction channel, the cross sections
      can be described with the usual optical potential variations, compatible with
      findings for (n, alpha) reactions in this mass range. Low-energy (alpha, gamma)
      and (alpha, n) data on other nuclei can also be consistently explained in this
      way. Since Coulomb excitation does not affect alpha emission, the
      148Gd(gamma,alpha) rate is much higher than previously assumed. This leads to
      very small 146Sm/144Sm stellar production ratios, in even more pronounced
      conflict with the meteorite data.

PMID- 23971553
TI  - Electromagnetic and gravitational outputs from binary-neutron-star coalescence.
AB  - The late stage of an inspiraling neutron-star binary gives rise to strong
      gravitational wave emission due to its highly dynamic, strong gravity. Moreover,
      interactions between the stellar magnetospheres can produce considerable
      electromagnetic radiation. We study this scenario using fully general
      relativistic, resistive magnetohydrodynamic simulations. We show that these
      interactions extract kinetic energy from the system, dissipate heat, and power
      radiative Poynting flux, as well as develop current sheets. Our results indicate
      that this power can (i) outshine pulsars in binaries, (ii) display a distinctive
      angular- and time-dependent pattern, and (iii) radiate within large opening
      angles. These properties suggest that some binary neutron-star mergers are ideal
      candidates for multimessenger astronomy. 

PMID- 23971554
TI  - Highly eccentric Kozai mechanism and gravitational-wave observation for neutron
      star binaries.
AB  - The Kozai mechanism for a hierarchical triple system could reduce the merger time
      of inner eccentric binary emitting gravitational waves (GWs) and has been
      qualitatively explained with the secular theory that is derived by averaging
      short-term orbital revolutions. However, with the secular theory, the minimum
      value of the inner pericenter distance could be excessively limited by the
      averaging operation. Compared with traditional predictions, the actual evolution
      of an eccentric inner binary could be accompanied by (i) a higher characteristic
      frequency of the pulselike GWs around its pericenter passages and (ii) a larger
      residual eccentricity at its final inspiral phase. These findings would be
      important for GW astronomy with the forthcoming advanced detectors. 

PMID- 23971555
TI  - Massive gravity coupled to Galileons is ghost-free.
AB  - It is possible to couple Dirac-Born-Infeld scalars possessing generalized
      Galilean internal shift symmetries (Galileons) to nonlinear massive gravity in
      four dimensions, in such a manner that the interactions maintain the Galilean
      symmetry. Such a construction is of interest, because it is not possible to
      couple such fields to massless general relativity in the same way. We show that
      this theory has the primary constraint necessary to eliminate the Boulware-Deser
      ghost, thus preserving the attractive properties of both the Galileons and ghost
      free massive gravity. 

PMID- 23971556
TI  - Origin of cosmic magnetic fields.
AB  - We calculate, in the free Maxwell theory, the renormalized quantum vacuum
      expectation value of the two-point magnetic correlation function in de Sitter
      inflation. We find that quantum magnetic fluctuations remain constant during
      inflation instead of being washed out adiabatically, as usually assumed in the
      literature. The quantum-to-classical transition of super-Hubble magnetic modes
      during inflation allow us to treat the magnetic field classically after
      reheating, when it is coupled to the primeval plasma. The actual magnetic field
      is scale independent and has an intensity of few*10(-12)  G if the energy scale
      of inflation is few*10(16)  GeV. Such a field accounts for galactic and galaxy
      cluster magnetic fields.

PMID- 23971557
TI  - Spontaneous breaking of flavor symmetry avoids the strong CP problem.
AB  - A promising approach to the standard model flavor puzzle is based on the idea
      that the SU(3)3 quark-flavor symmetry is spontaneously broken by vacuum
      expectation values of "Yukawa fields" which minimize the symmetry invariant
      scalar potential at configurations corresponding to the observed quark masses and
      mixing angles. We show that this approach provides a simple and elegant
      explanation for CP conservation in strong interactions.

PMID- 23971558
TI  - Probing dark matter at the LHC using vector boson fusion processes.
AB  - Vector boson fusion processes at the Large Hadron Collider (LHC) provide a unique
      opportunity to search for new physics with electroweak couplings. A feasibility
      study for the search of supersymmetric dark matter in the final state of two
      vector boson fusion jets and large missing transverse energy is presented at 14
      TeV. Prospects for determining the dark matter relic density are studied for the
      cases of wino and bino-Higgsino dark matter. The LHC could probe wino dark matter
      with mass up to approximately 600 GeV with a luminosity of 1000  fb(-1).

PMID- 23971559
TI  - Higgs seesaw mechanism as a source for dark energy.
AB  - Motivated by the seesaw mechanism for neutrinos which naturally generates small
      neutrino masses, we explore how a small grand-unified-theory-scale mixing between
      the standard model Higgs boson and an otherwise massless hidden sector scalar can
      naturally generate a small mass and vacuum expectation value for the new scalar
      which produces a false vacuum energy density contribution comparable to that of
      the observed dark energy dominating the current expansion of the Universe. This
      provides a simple and natural mechanism for producing the correct scale for dark
      energy, even if it does not address the long-standing question of why much larger
      dark energy contributions are not produced from the visible sector. The new
      scalar produces no discernible signatures in existing terrestrial experiments so
      that one may have to rely on other cosmological tests of this idea. 

PMID- 23971560
TI  - Physics performance of a low-luminosity low energy neutrino factory.
AB  - We investigate the minimal performance, in terms of beam luminosity and detector
      size, of a neutrino factory to achieve a competitive physics reach for the
      determination of the mass hierarchy and the discovery of leptonic CP violation.
      We find that a low luminosity of 2*10(20) useful muon decays per year and 5 GeV
      muon energy aimed at a 10 kton magnetized liquid argon detector placed at 1300 km
      from the source provides a good starting point. This result relies on theta13
      being large and assumes that the so-called platinum channel can be used
      effectively. We find that such a minimal facility would perform significantly
      better than phase I of the LBNE project and thus could constitute a reasonable
      step towards a full neutrino factory.

PMID- 23971561
TI  - Use of B->J/psi f0 decays to discern the qq or tetraquark nature of scalar
      mesons.
AB  - We consider the relative decay rates of B(0) and Bs(0) mesons into a J/psi plus a
      light scalar meson, either the f0(500) (sigma) or the f0(980). We show that it is
      possible to distinguish between the quark content of the scalars being quark
      antiquark or tetraquark by measuring specific ratios of decay rates. Using
      current data we determine the ratio of form factors in Bs(0)->J/psif0(980) with
      respect to B(0)->J/psif0(500) decays to be 0.99(-0.04)(+0.13) at a four-momentum
      transfer squared equal to the mass of the J/psi meson squared. In the case where
      these light mesons are considered to be quark-antiquark states, we give a
      determination of the mixing angle between strange and light quark states of less
      than 29 degrees  at 90% confidence level. We also discuss the use of a similar
      ratio to investigate the structure of other isospin singlet states.

PMID- 23971563
TI  - Bottom-quark forward-backward asymmetry in the standard model and beyond.
AB  - We computed the bottom-quark forward-backward asymmetry at the Tevatron in the
      standard model (SM) and for several new physics scenarios. Near the Z pole, the
      SM bottom asymmetry is dominated by tree level exchanges of electroweak gauge
      bosons. While above the Z pole, next-to-leading order QCD dominates the SM
      asymmetry as was the case with the top-quark forward-backward asymmetry. Light
      new physics, M(NP)?150  GeV, can cause significant deviations from the SM
      prediction for the bottom asymmetry. The bottom asymmetry can be used to
      distinguish between competing new physics (NP) explanations of the top asymmetry
      based on how the NP interferes with s-channel gluon and Z exchange.

PMID- 23971565
TI  - Freeze-out parameters: lattice meets experiment.
AB  - We present our results for ratios of higher order fluctuations of electric charge
      as functions of the temperature. These results are obtained in a system of 2+1
      quark flavors at physical quark masses and continuum extrapolated. We compare
      them to preliminary data on higher order moments of the net electric charge
      distribution from the STAR collaboration. This allows us to determine the freeze
      out temperature and chemical potential from first principles. We also show
      continuum-extrapolated results for ratios of higher order fluctuations of baryon
      number. These will allow us to test the consistency of the approach, by comparing
      them to the corresponding experimental data (once they become available) and
      thus, extracting the freeze-out parameters in an independent way. 

PMID- 23971564
TI  - Accurate test of chiral dynamics in the gammap->pi0p reaction.
AB  - A precision measurement of the differential cross sections dsigma/dOmega and the
      linearly polarized photon asymmetry Sigma=(dsigma?-dsigma?)/(dsigma?+dsigma?) for
      the gammap->pi0p reaction in the near-threshold region has been performed with a
      tagged photon beam and almost 4pi detector at the Mainz Microtron. The Glasgow
      Mainz photon tagging facility along with the Crystal Ball/TAPS multiphoton
      detector system and a cryogenic liquid hydrogen target were used. These data
      allowed for a precise determination of the energy dependence of the real parts of
      the S- and all three P-wave amplitudes for the first time and provide the most
      stringent test to date of the predictions of chiral perturbation theory and its
      energy region of agreement with experiment.

PMID- 23971566
TI  - Evidence from lattice data for a new particle on the worldsheet of the QCD flux
      tube.
AB  - We propose a new approach for the calculation of the spectrum of excitations of
      QCD flux tubes. It relies on the fact that the worldsheet theory is integrable at
      low energies. With this approach, energy levels can be calculated for much
      shorter flux tubes than was previously possible, allowing for a quantitative
      comparison with existing lattice data. The improved theoretical control makes it
      manifest that existing lattice data provides strong evidence for a new
      pseudoscalar particle localized on the QCD flux tube--the worldsheet axion.

PMID- 23971562
TI  - Precision measurement of charged pion and kaon differential cross sections in e+
      e- annihilation at sqrt[s]=10.52  GeV.
AB  - Measurements of inclusive differential cross sections for charged pion and kaon
      production in e+ e- annihilation have been carried out at a center-of-mass energy
      of sqrt[s]=10.52  GeV. The measurements were performed with the Belle detector at
      the KEKB e+ e- collider using a data sample containing 113*10(6) e+ e- -> qq
      events, where q={u,d,s,c}. We present charge-integrated differential cross
      sections dsigma(h+/-)/dz for h+/-={pi+/-,K+/-} as a function of the relative
      hadron energy z=2E(h)/sqrt[s] from 0.2 to 0.98. The combined statistical and
      systematic uncertainties for pi+/- (K+/-) are 4% (4%) at z~0.6 and 15% (24%) at
      z~0.9. The cross sections are the first measurements of the z dependence of pion
      and kaon production for z>0.7 as well as the first precision cross section
      measurements at a center-of-mass energy far below the Z0 resonance used by the
      experiments at LEP and SLC.

PMID- 23971567
TI  - Medium modification of gamma jets in high-energy heavy-ion collisions.
AB  - Two puzzling features in the experimental study of jet quenching in central Pb+Pb
      collisions at the LHC are explained within a linearized Boltzmann transport model
      for jet propagation. A gamma-tagged jet is found to lose about 15% of its initial
      energy while its azimuthal angle remains almost unchanged due to rapid cooling of
      the medium. The reconstructed jet fragmentation function is found to have some
      modest enhancement at both small and large fractional momenta as compared to that
      in the vacuum because of the increased contribution of leading particles to the
      reconstructed jet energy and induced gluon radiation and recoiled partons. A
      gamma-tagged jet fragmentation function is proposed that is more sensitive to jet
      medium interaction and the jet transport parameter in the medium. The effects of
      recoiled medium partons on the reconstructed jets are also discussed. 

PMID- 23971568
TI  - Isotopic chains around oxygen from evolved chiral two- and three-nucleon
      interactions.
AB  - We extend the formalism of self-consistent Green's function theory to include
      three-body interactions and apply it to isotopic chains around oxygen for the
      first time. The third-order algebraic diagrammatic construction equations for two
      body Hamiltonians can be exploited upon defining system-dependent one- and two
      body interactions coming from the three-body force, and, correspondingly,
      dropping interaction-reducible diagrams. The Koltun sum rule for the total
      binding energy acquires a correction due to the added three-body interaction.
      This formalism is then applied to study chiral two- and three-nucleon forces
      evolved to low momentum cutoffs. The binding energies of nitrogen, oxygen, and
      fluorine isotopes are reproduced with good accuracy and demonstrate the
      predictive power of this approach. Leading order three-nucleon forces
      consistently bring results close to the experiment for all neutron rich isotopes
      considered and reproduce the correct driplines for oxygen and nitrogen. The
      formalism introduced also allows us to calculate form factors for nucleon
      transfer on doubly magic systems. 

PMID- 23971569
TI  - Electromagnetic transition from the 4+ to 2+ resonance in 8Be measured via the
      radiative capture in 4He + 4He.
AB  - An earlier measurement on the 4+ to 2+ radiative transition in 8Be provided the
      first electromagnetic signature of its dumbbell-like shape. However, the large
      uncertainty in the measured cross section does not allow a stringent test of
      nuclear structure models. This Letter reports a more elaborate and precise
      measurement for this transition, via the radiative capture in the 4He + 4He
      reaction, improving the accuracy by about a factor of 3. Ab initio calculations
      of the radiative transition strength with improved three-nucleon forces are also
      presented. The experimental results are compared with the predictions of the
      alpha cluster model and ab initio calculations.

PMID- 23971570
TI  - Atom-based vector microwave electrometry using rubidium Rydberg atoms in a vapor
      cell.
AB  - It is clearly important to pursue atomic standards for quantities like
      electromagnetic fields, time, length, and gravity. We have recently shown using
      Rydberg states that Rb atoms in a vapor cell can serve as a practical, compact
      standard for microwave electric field strength. Here we demonstrate for the first
      time that Rb atoms excited in a vapor cell can also be used for vector microwave
      electrometry by using Rydberg-atom electromagnetically induced transparency. We
      describe the measurements necessary to obtain an arbitrary microwave electric
      field polarization at a resolution of 0.5 degrees . We compare the experiments to
      theory and find them to be in excellent agreement. 

PMID- 23971571
TI  - Slow thermalization between a lattice and free Bose gas.
AB  - Using a 3D spin-dependent optical lattice, we study thermalization and energy
      exchange between two ultracold Bose gases, one of which is strongly correlated
      and bound to the lattice and another that is free from the lattice potential.
      Disruption of interspecies thermalization is revealed through measurements of
      condensate fraction after the lattice is superimposed on the parabolic confining
      potential. By selectively heating the lattice-bound species and measuring the
      rate of heat transfer to the free state, suppression of energy exchange is
      observed. Comparison with a Fermi's golden rule prediction confirms that this
      effect is caused by a dispersion mismatch that reduces the phase space available
      for elastic collisions. This result has critical implications for methods
      proposed to cool strongly correlated lattice gases. 

PMID- 23971572
TI  - Quantum superposition of target and product states in reactive electron
      scattering from CF4 revealed through velocity slice imaging.
AB  - Exploiting the technique of velocity slice imaging, we have performed a detailed
      study of reactive electron scattering with CF4. We have measured the electron
      impact energy dependence of both the angular and kinetic energy distributions of
      the channels yielding F- and CF3(-) anions. These data provide an unprecedented
      insight into the quantum superposition of the target state and product channels,
      respectively, of Td and C3v symmetry, and shed new light on the dissociation
      dynamics.

PMID- 23971573
TI  - Single-photon transistor in circuit quantum electrodynamics.
AB  - We introduce a circuit quantum electrodynamical setup for a "single-photon"
      transistor. In our approach photons propagate in two open transmission lines that
      are coupled via two interacting transmon qubits. The interaction is such that no
      photons are exchanged between the two transmission lines but a single photon in
      one line can completely block or enable the propagation of photons in the other
      line. High on-off ratios can be achieved for feasible experimental parameters.
      Our approach is inherently scalable as all photon pulses can have the same pulse
      shape and carrier frequency such that output signals of one transistor can be
      input signals for a consecutive transistor. 

PMID- 23971574
TI  - Filtering random matrices: the effect of incomplete channel control in multiple
      scattering.
AB  - We present an analytic random matrix theory for the effect of incomplete channel
      control on the measured statistical properties of the scattering matrix of a
      disordered multiple-scattering medium. When the fraction of the controlled input
      channels, m1, and output channels, m2, is decreased from unity, the density of
      the transmission eigenvalues is shown to evolve from the bimodal distribution
      describing coherent diffusion, to the distribution characteristic of uncorrelated
      Gaussian random matrices, with a rapid loss of access to the open eigenchannels.
      The loss of correlation is also reflected in an increase in the information
      capacity per channel of the medium. Our results have strong implications for
      optical and microwave experiments on diffusive scattering media.

PMID- 23971575
TI  - Nonequilibrium chaos of disordered nonlinear waves.
AB  - Do nonlinear waves destroy Anderson localization? Computational and experimental
      studies yield subdiffusive nonequilibrium wave packet spreading. Chaotic dynamics
      and phase decoherence assumptions are used for explaining the data. We perform a
      quantitative analysis of the nonequilibrium chaos assumption and compute the time
      dependence of main chaos indicators--Lyapunov exponents and deviation vector
      distributions. We find a slowing down of chaotic dynamics, which does not cross
      over into regular dynamics up to the largest observed time scales, still being
      fast enough to allow for a thermalization of the spreading wave packet. Strongly
      localized chaotic spots meander through the system as time evolves. Our findings
      confirm for the first time that nonequilibrium chaos and phase decoherence
      persist, fueling the prediction of a complete delocalization.

PMID- 23971576
TI  - Flow-induced draping.
AB  - Crumpled paper or drapery patterns are everyday examples of how elastic sheets
      can respond to external forcing. In this Letter, we study experimentally a
      different sort of forcing. We consider a circular flexible plate clamped at its
      center and subject to a uniform flow normal to its initial surface. As the flow
      velocity is gradually increased, the plate exhibits a rich variety of bending
      deformations: from a cylindrical shape, to isometric developable cones with
      azimuthal periodicity two or three, to eventually a rolled-up period-three cone.
      We show that this sequence of flow-induced deformations can be qualitatively
      predicted by a linear analysis based on the balance between elastic energy and
      pressure force work. 

PMID- 23971577
TI  - Spatial fluctuations of fluid velocities in flow through a three-dimensional
      porous medium.
AB  - We use confocal microscopy to directly visualize the spatial fluctuations in
      fluid flow through a three-dimensional porous medium. We find that the velocity
      magnitudes and the velocity components both along and transverse to the imposed
      flow direction are exponentially distributed, even with residual trapping of a
      second immiscible fluid. Moreover, we find pore-scale correlations in the flow
      that are determined by the geometry of the medium. Our results suggest that
      despite the considerable complexity of the pore space, fluid flow through it is
      not completely random. 

PMID- 23971578
TI  - Exploiting lens aberrations to create electron-vortex beams.
AB  - A model for a new electron-vortex beam production method is proposed and
      experimentally demonstrated. The technique calls on the controlled manipulation
      of the degrees of freedom of the lens aberrations to achieve a helical phase
      front. These degrees of freedom are accessible by using the corrector lenses of a
      transmission electron microscope. The vortex beam is produced through a
      particular alignment of these lenses into a specifically designed astigmatic
      state and applying an annular aperture in the condenser plane. Experimental
      results are found to be in good agreement with simulations. 

PMID- 23971579
TI  - Magnetic field blocks two-dimensional crystallization in strongly coupled
      plasmas.
AB  - Crystallization in a two-dimensional strongly coupled plasma from a rapidly
      cooled fluid is found to be efficiently blocked by an external magnetic field.
      Beyond a threshold of the magnetic field strength B, the relaxation time to the
      equilibrium crystal increases exponentially with B, which is attributed to an
      impeded conversion of potential to kinetic energy. Our finding is opposed to the
      standard picture of two-dimensional freezing of one-component systems which does
      not exhibit a nucleation barrier and opens the way to keep two-dimensional fluids
      metastable over long times. 

PMID- 23971580
TI  - Generating "superponderomotive" electrons due to a non-wake-field interaction
      between a laser pulse and a longitudinal electric field.
AB  - It is shown that electrons with momenta exceeding the "free electron" limit of
      m(e)ca(0)(2)/2 can be produced when a laser pulse and a longitudinal electric
      field interact with an electron via a non-wake-field mechanism. The mechanism
      consists of two stages: the reduction of the electron dephasing rate gamma -
      p(x)/m(e)c by an accelerating region of electric field and electron acceleration
      by the laser via the Lorentz force. This mechanism can, in principle, produce
      electrons that have longitudinal momenta that is a significant multiple of
      m(e)ca(0)(2)/2. 2D particle-in-cell simulations of a relatively simple laser
      plasma interaction indicate that the generation of superponderomotive electrons
      is strongly affected by this "antidephasing" mechanism.

PMID- 23971581
TI  - Measurement of high-pressure shock waves in cryogenic deuterium-tritium ice
      layered capsule implosions on NIF.
AB  - The first measurements of multiple, high-pressure shock waves in cryogenic
      deuterium-tritium (DT) ice layered capsule implosions on the National Ignition
      Facility have been performed. The strength and relative timing of these shocks
      must be adjusted to very high precision in order to keep the DT fuel entropy low
      and compressibility high. All previous measurements of shock timing in inertial
      confinement fusion implosions [T. R. Boehly et al., Phys. Rev. Lett. 106, 195005
      (2011), H. F. Robey et al., Phys. Rev. Lett. 108, 215004 (2012)] have been
      performed in surrogate targets, where the solid DT ice shell and central DT gas
      regions were replaced with a continuous liquid deuterium (D2) fill. This report
      presents the first experimental validation of the assumptions underlying this
      surrogate technique. 

PMID- 23971582
TI  - Solid iron compressed up to 560 GPa.
AB  - Dynamic compression by multiple shocks is used to compress iron up to 560 GPa
      (5.6 Mbar), the highest solid-state pressure yet attained for iron in the
      laboratory. Extended x-ray absorption fine structure (EXAFS) spectroscopy offers
      simultaneous density, temperature, and local-structure measurements for the
      compressed iron. The data show that the close-packed structure of iron is stable
      up to 560 GPa, the temperature at peak compression is significantly higher than
      expected from pure compressive work, and the dynamic strength of iron is many
      times greater than the static strength based on lower pressure data. The results
      provide the first constraint on the melting line of iron above 400 GPa. 

PMID- 23971583
TI  - Thermodynamic equilibrium conditions of graphene films on SiC.
AB  - First-principles surface phase diagrams reveal that epitaxial monolayer graphene
      films on the Si side of 3C-SiC(111) can exist as thermodynamically stable phases
      in a narrow range of experimentally controllable conditions, defining a path to
      the highest quality graphene films. Our calculations are based on a van der Waals
      corrected density functional. The full, experimentally observed
      (6sqrt[3]*6sqrt[3])-R30 degrees  supercells for zero- to trilayer graphene are
      essential to describe the correct interface geometries and the relative stability
      of surface phases and possible defects. 

PMID- 23971584
TI  - Counting dislocations in microcrystals by coherent x-ray diffraction.
AB  - We present here an unprecedented way of quantifying the number of dislocations in
      microcrystals. This method relies on a combination of several state-of-the-art
      techniques: coherent x-ray diffraction used as a local probe, together with the
      controlled compression of micro-objects. We demonstrate that by using this
      method, dislocations in the microcrystal can be detected and their number
      precisely quantified. This cannot be done with other techniques in a
      nondestructive way. Our method opens a route for the study of many small-scale
      systems with defect-dependent physical properties and it could become a critical
      tool for addressing future challenges in nanotechnology. 

PMID- 23971585
TI  - Enhanced sputtering yields from single-ion impacts on gold nanorods.
AB  - Sputtering yields, enhanced by more than an order of magnitude, have been
      observed for 80 keV Xe ion irradiation of monocrystalline Au nanorods. Yields are
      in the range 100-1900  atoms/ion compared with values for a flat surface of ~50.
      This enhancement results in part from the proximity of collision cascades and
      ensuing thermal spikes to the nanorod surfaces. Molecular dynamic modeling
      reveals that the range of incident angles occurring for irradiation of nanorods
      and the larger number of atoms in "explosively ejected" atomic clusters make a
      significant contribution to the enhanced yield. 

PMID- 23971586
TI  - Hydrogenation and disorder in engineered black TiO2.
AB  - A new form of TiO2 which is black in color has been shown to exhibit high
      efficiency for photocatalytic reactions under solar radiation [X. Chen, L. Liu,
      P. Y. Yu, and S. S. Mao, Science 331, 746 (2011)]. However, the mechanism behind
      this disorder-engineering process is not fully understood. In this Letter, based
      on density functional theory, we describe the role of hydrogen in producing
      lattice disorder in the anatase nanocrystals. We clarify further that the highly
      localized nature of the midgap states results in spatial separation of
      photoexcited electrons and holes in black TiO2, and that accounts for its high
      photocatalytic efficiency.

PMID- 23971587
TI  - Direct detection of electron backscatter diffraction patterns.
AB  - We report the first use of direct detection for recording electron backscatter
      diffraction patterns. We demonstrate the following advantages of direct
      detection: the resolution in the patterns is such that higher order features are
      visible; patterns can be recorded at beam energies below those at which
      conventional detectors usefully operate; high precision in cross-correlation
      based pattern shift measurements needed for high resolution electron backscatter
      diffraction strain mapping can be obtained. We also show that the physics
      underlying direct detection is sufficiently well understood at low primary
      electron energies such that simulated patterns can be generated to verify our
      experimental data. 

PMID- 23971588
TI  - Estimate of the maximum strength of metallic glasses from finite deformation
      theory.
AB  - Maximum strength sets the limit of a material's intrinsic resistance to permanent
      deformation. Its significance, however, lies not in the highest strength value
      that a solid can possibly achieve, but rather in how this quantity is degraded,
      from which one could decipher the underlying mechanisms of yielding in a real
      material. A wide range of maximum strength values have been measured
      experimentally for metallic glasses. However, the true maximum strength remains
      unknown to date. Here, using finite deformation theory, we give the first
      theoretical estimate of the ultimate strength of metallic glasses. Our
      theoretical results, along with those from experiment and simulation, lead us to
      several mechanisms of degradation of the theoretical strength that are closely
      connected to correlated atomic motion with varying characteristic length in real
      metallic glasses. 

PMID- 23971589
TI  - Bulk and surface tunneling hydrogen defects in alumina.
AB  - We perform ab initio calculations of hydrogen-based tunneling defects in alumina
      to identify deleterious two-level systems (TLS) in superconducting qubits. The
      defects analyzed include bulk hydrogenated Al vacancies, bulk hydrogen
      interstitial defects, and a surface OH rotor. The formation energies of the
      defects are first computed for an Al- and O-rich environment to give the
      likelihood of defect occurrence during growth. The potential energy surfaces are
      then computed and the corresponding dipole moments are evaluated to determine the
      coupling of the defects to an electric field. Finally, the tunneling energy is
      computed for the hydrogen defect and the analogous deuterium defect, providing an
      estimate of the TLS energy and the corresponding frequency for photon absorption.
      We predict that hydrogenated cation vacancy defects will form a significant
      density of GHz frequency TLSs in alumina. 

PMID- 23971590
TI  - Elastic signature of flow events in supercooled liquids under shear.
AB  - Using numerical simulation of a 2D Lennard-Jones system, we study the crossover
      from shear thinning to Newtonian flow. We find that the short-time elastic
      response of our system essentially does not change through this crossover, and
      show that, in the Newtonian regime, thermal activation triggers shear
      transformations, i.e., local irreversible shear events that produce Eshelby (long
      ranged, anisotropic) deformation fields as previously seen in low-T glasses.
      Quite surprisingly, these Eshelby fields are found to persist much beyond the
      alpha-relaxation time, and shear thinning to coincide with the emergence of
      correlations between shear relaxation centers. 

PMID- 23971591
TI  - Stick-slip sliding of water drops on chemically heterogeneous surfaces.
AB  - We present a comprehensive study of water drops sliding down chemically
      heterogeneous surfaces formed by a periodic pattern of alternating hydrophobic
      and hydrophilic stripes. Drops are found to undergo a stick-slip motion whose
      average speed is an order of magnitude smaller than that measured on a
      homogeneous surface having the same static contact angle. This motion is the
      result of the periodic deformations of the drop interface when crossing the
      stripes. Numerical simulations confirm this view and are used to elucidate the
      principles underlying the experimental observations. 

PMID- 23971592
TI  - Finite-temperature hydrogen adsorption and desorption thermodynamics driven by
      soft vibration modes.
AB  - It has been widely accepted that enhanced dihydrogen adsorption is required for
      room-temperature hydrogen storage on nanostructured porous materials. Here we
      report, based on results of first-principles total energy and vibrational
      spectrum calculations, finite-temperature adsorption and desorption
      thermodynamics of hydrogen molecules that are adsorbed on the metal center of
      metal-porphyrin-incorporated graphene. We have revealed that the room-temperature
      hydrogen storage is achievable not only with the enhanced adsorption enthalpy,
      but also with soft-mode driven vibrational entropy of the adsorbed dihydrogen
      molecule. The soft vibration modes mostly result from multiple orbital coupling
      between the hydrogen molecule and the buckled metal center, for example, in Ca
      porphyrin-incorporated graphene. Our study suggests that the current design
      strategy for room-temperature hydrogen storage materials should be modified with
      explicitly taking the finite-temperature vibration thermodynamics into account. 

PMID- 23971593
TI  - Bonding and structure of ceramic-ceramic interfaces.
AB  - Quantum molecular dynamics simulations of alpha-Al2O3(0001)/3C-SiC(111)
      interfaces reveal profound effects of thermal annealing for producing strong
      interfaces consisting solely of cation-anion bonds and their consequence on
      interfacial structures. A Si-terminated SiC surface and Al2O3 form a stronger
      interface (Si-interface) with a Si-O bond density of 12.2  nm(-2), whereas the C
      interface has an Al-C bond density of 9.46  nm(-2). The interfacial bond
      strengthening is accompanied by the formation of an Al2O3 interphase with a
      thickness of 2-8 A. Such atomistic understanding may help rational interfacial
      design of high-temperature ceramic composites for broad applications such as
      power generation systems.

PMID- 23971594
TI  - Dimerized solids and resonating plaquette order in SU(N)-Dirac fermions.
AB  - We study the quantum phases of fermions with an explicit SU(N)-symmetric,
      Heisenberg-like nearest-neighbor flavor exchange interaction on the honeycomb
      lattice at half filling. Employing projective (zero temperature) quantum Monte
      Carlo simulations for even values of N, we explore the evolution from a weak
      coupling semimetal into the strong-coupling, insulating regime. Furthermore, we
      compare our numerical results to a saddle-point approximation in the large-N
      limit. From the large-N regime down to the SU(6) case, the insulating state is
      found to be a columnar valence bond crystal, with a direct transition to the
      semimetal at weak, finite coupling, in agreement with the mean-field result in
      the large-N limit. At SU(4) however, the insulator exhibits a subtly different
      valence bond crystal structure, stabilized by resonating valence bond plaquettes.
      In the SU(2) limit, our results support a direct transition between the semimetal
      and an antiferromagnetic insulator. 

PMID- 23971595
TI  - Angular-momentum-dependent orbital-free density functional theory.
AB  - Orbital-free (OF) density functional theory (DFT) directly solves for the
      electron density rather than the wave function of many electron systems, greatly
      simplifying and enabling large scale first principles simulations. However, the
      required approximate noninteracting kinetic energy density functionals and local
      electron-ion pseudopotentials severely restrict the general applicability of
      conventional OFDFT. Here, we present a new generation of OFDFT called angular
      momentum-dependent (AMD)-OFDFT to harness the accuracy of Kohn-Sham DFT and the
      simplicity of OFDFT. The angular momenta of electrons are explicitly introduced
      within atom-centered spheres so that the important ionic core region can be
      accurately described. In addition to conventional OF total energy functionals, we
      introduce a crucial nonlocal energy term with a set of AMD energies to correct
      errors due to the kinetic energy density functional and the local
      pseudopotential. We find that our AMD-OFDFT formalism offers substantial
      improvements over conventional OFDFT, as we show for various properties of the
      transition metal titanium. 

PMID- 23971596
TI  - Multifractality at Anderson transitions with Coulomb interaction.
AB  - We explore mesoscopic fluctuations and correlations of the local density of
      states (LDOS) near localization transition in a disordered interacting electronic
      system. It is shown that the LDOS multifractality survives in the presence of the
      Coulomb interaction. We calculate the spectrum of multifractal dimensions in
      2+epsilon spatial dimensions and show that it differs from that in the absence of
      interaction. The multifractal character of fluctuations and correlations of the
      LDOS can be studied experimentally by scanning tunneling microscopy of two
      dimensional and three-dimensional disordered structures. 

PMID- 23971597
TI  - Inverse spin Hall effect in a ferromagnetic metal.
AB  - The inverse spin Hall effect (ISHE) has been observed only in nonmagnetic metals,
      such as Pt and Au, with a strong spin-orbit coupling. We report the observation
      of ISHE in a ferromagnetic permalloy (Py) on ferromagnetic insulator yttrium iron
      garnet (YIG). Through controlling the spin current injection by altering the Py
      YIG interface, we have isolated the spin current contribution and demonstrated
      the ISHE in a ferromagnetic metal, the reciprocal phenomenon of the anomalous
      Hall effect. A large spin Hall angle in Py, determined from Py thin films of
      different thicknesses, indicates many other ferromagnetic metals may be exploited
      as superior pure spin current detectors and for applications in spin current. 

PMID- 23971598
TI  - Spin-orbital texture in topological insulators.
AB  - For three-dimensional topological insulators in the Bi2Se3 family, topological
      surface states with p(z) orbitals have a left-handed spin texture for the upper
      Dirac cone and a right-handed spin texture for the lower Dirac cone. In this
      work, we predict a new form of the spin-orbital texture associated with the p(x)
      and p(y) orbitals. For the upper Dirac cone, a left-handed (right-handed) spin
      texture is coupled to the "radial" ("tangential") orbital texture, whereas for
      the lower Dirac cone, the coupling of spin and orbital textures is the exact
      opposite. The "tangential" ("radial") orbital texture is dominant for the upper
      (lower) Dirac cone, leading to the right-handed spin texture for the in-plane
      orbitals of both the upper and lower Dirac cones. A spin-resolved and photon
      polarized angle-resolved photoemission spectroscopy experiment is proposed to
      observe this novel spin-orbital texture.

PMID- 23971599
TI  - Pauli spin blockade and the ultrasmall magnetic field effect.
AB  - Based on the spin-blockade model for organic magnetoresistance, we present an
      analytic expression for the polaron-bipolaron transition rate, taking into
      account the effective nuclear fields on the two sites. We reveal the physics
      behind the qualitatively different magnetoconductance line shapes observed in
      experiment, as well as the ultrasmall magnetic field effect (USFE). Since our
      findings agree in detail with recent experiments, they also indirectly provide
      support for the spin-blockade interpretation of organic magnetoresistance. In
      addition, we predict the existence of a similar USFE in semiconductor double
      quantum dots tuned to the spin-blockade regime. 

PMID- 23971600
TI  - Chiral tunneling in a twisted graphene bilayer.
AB  - The perfect transmission in a graphene monolayer and the perfect reflection in a
      Bernal graphene bilayer for electrons incident in the normal direction of a
      potential barrier are viewed as two incarnations of the Klein paradox. Here we
      show a new and unique incarnation of the Klein paradox. Owing to the different
      chiralities of the quasiparticles involved, the chiral fermions in a twisted
      graphene bilayer show an adjustable probability of chiral tunneling for normal
      incidence: they can be changed from perfect tunneling to partial or perfect
      reflection, or vice versa, by controlling either the height of the barrier or the
      incident energy. As well as addressing basic physics about how the chiral
      fermions with different chiralities tunnel through a barrier, our results provide
      a facile route to tune the electronic properties of the twisted graphene bilayer.

PMID- 23971601
TI  - d+id' chiral superconductivity in bilayer silicene.
AB  - We investigate the structure and physical properties of the undoped bilayer
      silicene through first-principles calculations and find the system is
      intrinsically metallic with sizable pocket Fermi surfaces. When realistic
      electron-electron interaction turns on, the system is identified as a chiral
      d+id' topological superconductor mediated by the strong spin fluctuation on the
      border of the antiferromagnetic spin density wave order. Moreover, the tunable
      Fermi pocket area via strain makes it possible to adjust the spin density wave
      critical interaction strength near the real one and enables a high
      superconducting critical temperature.

PMID- 23971602
TI  - Realization of artificial ice systems for magnetic vortices in a superconducting
      MoGe thin film with patterned nanostructures.
AB  - We report an anomalous matching effect in MoGe thin films containing pairs of
      circular holes arranged in such a way that four of those pairs meet at each
      vertex point of a square lattice. A remarkably pronounced fractional matching was
      observed in the magnetic field dependences of both the resistance and the
      critical current. At the half matching field the critical current can be even
      higher than that at zero field. This has never been observed before for vortices
      in superconductors with pinning arrays. Numerical simulations within the
      nonlinear Ginzburg-Landau theory reveal a square vortex ice configuration in the
      ground state at the half matching field and demonstrate similar characteristic
      features in the field dependence of the critical current, confirming the
      experimental realization of an artificial ice system for vortices for the first
      time. 

PMID- 23971603
TI  - Waiting time distributions for the transport through a quantum-dot tunnel coupled
      to one normal and one superconducting lead.
AB  - We have studied the waiting time distributions (WTDs) for subgap transport
      through a single-level quantum-dot tunnel coupled to one normal and one
      superconducting lead. The WTDs reveal the internal dynamics of the system, in
      particular, the coherent transfer of Cooper pairs between the dot and the
      superconductor. The WTDs exhibit oscillations that can be directly associated to
      the coherent oscillation between the empty and doubly occupied dot. The
      oscillation frequency is equal to the energy splitting between the Andreev bound
      states. These effects are more pronounced when the empty state and double
      occupied state are in resonance. 

PMID- 23971604
TI  - Microwave spectroscopy evidence of superconducting pairing in the magnetic-field
      induced metallic state of InO(x) films at zero temperature.
AB  - We investigate the field-tuned quantum phase transition in a 2D low-disorder
      amorphous InO(x) film in the frequency range of 0.05 to 16 GHz employing
      microwave spectroscopy. In the zero-temperature limit, the ac data are consistent
      with a scenario where this transition is from a superconductor to a metal instead
      of a direct transition to an insulator. The intervening metallic phase is unusual
      with a small but finite resistance that is much smaller than the normal state
      sheet resistance at the lowest measured temperatures. Moreover, it exhibits a
      superconducting response on short length and time scales while global
      superconductivity is destroyed. We present evidence that the true quantum
      critical point of this 2D superconductor metal transition is located at a field
      B(sm) far below the conventionally defined critical field B(cross) where
      different isotherms of magnetoresistance cross each other. The superfluid
      stiffness in the low-frequency limit and the superconducting fluctuation
      frequency from opposite sides of the transition both vanish at B~B(sm). The lack
      of evidence for finite-frequency superfluid stiffness surviving B(cross)
      signifies that B(cross) is a crossover above which superconducting fluctuations
      make a vanishing contribution to dc and ac measurements.

PMID- 23971605
TI  - Nonequilibrium spin noise spectroscopy.
AB  - Spin noise spectroscopy is an experimental approach to obtain correlators of
      mesoscopic spin fluctuations in time by purely optical means. We explore the
      information that this technique can provide when it is applied to a weakly
      nonequilibrium regime when an electric current is driven through a sample by an
      electric field. We find that the noise power spectrum of conducting electrons
      experiences a shift, which is proportional to the strength of the spin-orbit
      coupling for electrons moving along the electric field direction. We propose
      applications of this effect to measurements of spin-orbit coupling anisotropy and
      separation of spin noise of conducting and localized electrons. 

PMID- 23971606
TI  - Reversal mechanism of an individual Ni nanotube simultaneously studied by torque
      and SQUID magnetometry.
AB  - Using an optimally coupled nanometer-scale SQUID, we measure the magnetic flux
      originating from an individual ferromagnetic Ni nanotube attached to a Si
      cantilever. At the same time, we detect the nanotube's volume magnetization using
      torque magnetometry. We observe both the predicted reversible and irreversible
      reversal processes. A detailed comparison with micromagnetic simulations suggests
      that vortexlike states are formed in different segments of the individual
      nanotube. Such stray-field free states are interesting for memory applications
      and noninvasive sensing. 

PMID- 23971607
TI  - Dynamics of an insulating Skyrmion under a temperature gradient.
AB  - We study the Skyrmion dynamics in thin films under a temperature gradient. Our
      numerical simulations show that both single and multiple Skyrmions in a crystal
      move towards the high temperature region, which is contrary to particle
      diffusion. Noticing a similar effect in the domain wall motion, we employ a
      theory based on magnon dynamics to explain this counterintuitive phenomenon.
      Unlike the temperature driven domain wall motion, the Skyrmion's topological
      charge plays an important role, and a transverse Skyrmion motion is observed. Our
      theory turns out to be in agreement with numerical simulations, both
      qualitatively and quantitatively. Our calculation indicates that a very promising
      Skyrmion dynamic phenomenon can be observed in experiments. 

PMID- 23971608
TI  - Spin pseudogap in Ni-doped SrCuO2.
AB  - The S=1/2 spin chain material SrCuO2 doped with 1% S=1 Ni impurities is studied
      by inelastic neutron scattering. At low temperatures, the spectrum shows a
      pseudogap Delta~8  meV, absent in the parent compound, and not related to any
      structural phase transition. The pseudogap is shown to be a generic feature of
      quantum spin chains with dilute defects. A simple model based on this idea
      quantitatively accounts for the experimental data measured in the temperature
      range from 2 to 300 K, and allows us to represent the momentum-integrated dynamic
      structure factor in a universal scaling form.

PMID- 23971609
TI  - Terahertz-induced optical emission of photoexcited undoped GaAs quantum wells.
AB  - Intense terahertz (THz) pulse induces photoluminescence (PL) flash from undoped
      high-quality GaAs/AlGaAs quantum wells under continuous wave laser excitation.
      The number of excitons increases 10,000-fold from that of the steady state under
      only laser excitation. The THz electric field dependence and the relaxation
      dynamics of the PL flash intensity suggest that the strong electric field of the
      THz pulse ionizes impurity states during the 1 ps period of the THz pulse and
      release carriers from a giant reservoir containing impurity states in the AlGaAs
      layers.

PMID- 23971610
TI  - Dependence of the minority-carrier lifetime on the stoichiometry of CdTe using
      time-resolved photoluminescence and first-principles calculations.
AB  - CdTe is one of the most promising materials for thin-film solar cells. However,
      further improvement of its performance is hindered by its relatively short
      minority-carrier lifetime. Combining theoretical calculations and experimental
      measurements, we find that for both intrinsic CdTe and CdTe solar cell devices,
      longer minority-carrier lifetimes can be achieved under Cd-rich conditions, in
      contrast to the previous belief that Te-rich conditions are more beneficial.
      First-principles calculations suggest that the dominant recombination centers
      limiting the minority-carrier lifetime are the Te antisite and Te interstitial.
      Therefore, we propose that to optimize the solar cell performance, extrinsic p
      type doping (e.g., N, P, or As substitution on Te sites) in CdTe under Cd-rich
      conditions should be a good approach to simultaneously increase both the minority
      carrier lifetime and hole concentration. 

PMID- 23971611
TI  - Auger processes mediating the nonresonant optical emission from a semiconductor
      quantum dot embedded inside an optical cavity.
AB  - We show that Auger processes involving wetting layer transitions mediate emission
      from a cavity that is detuned from a quantum dot by even tens of meV. The wetting
      layer thus acts as a reservoir, which by Coulomb scattering can supply or absorb
      the energy difference between emitter and cavity. We perform microscopic
      calculations of the effect treating the wetting layer as a non-Markovian
      reservoir interacting with the coupled quantum dot-cavity system through Coulomb
      interactions. Experimentally, cavity feeding has been observed in the asymmetric
      detuning range of -10 to +45  meV. We show that this asymmetry arises naturally
      from the quasiequilibrium properties of the wetting layer reservoir. Furthermore,
      we present numerical calculations of both photoluminescence spectra and photon
      correlations, demonstrating good qualitative agreement with experiments. 

PMID- 23971612
TI  - Detecting and polarizing nuclear spins with double resonance on a single electron
      spin.
AB  - We report the detection and polarization of nuclear spins in diamond at room
      temperature by using a single nitrogen-vacancy (NV) center. We use Hartmann-Hahn
      double resonance to coherently enhance the signal from a single nuclear spin
      while decoupling from the noisy spin bath, which otherwise limits the detection
      sensitivity. As a proof of principle, we (i) observe coherent oscillations
      between the NV center and a weakly coupled nuclear spin and (ii) demonstrate
      nuclear-bath cooling, which prolongs the coherence time of the NV sensor by more
      than a factor of 5. Our results provide a route to nanometer scale magnetic
      resonance imaging and novel quantum information processing protocols. 

PMID- 23971613
TI  - Nanoscale photoelectron mapping and spectroscopy with an atomic force microscope.
AB  - The tip of an atomic force microscope is used as a local probe for photoelectrons
      excited by laser illumination. The tip-sample distance is precisely controlled by
      the van der Waals force and the pure photoemission current is measured without
      tunneling current contribution. The nanoscale photoelectron mapping with high
      current contrast is obtained on a cesium covered Au(111) surface. By sweeping the
      laser photon energy, the local photoelectron spectra are measured on Cs islands
      and terraces. The results reveal distinct electronic states and photoemission
      thresholds for different Cs coverage, providing the photoemission current
      contrast mechanism. The contrast in photoelectron mapping can be further tuned by
      the incident laser polarization exploiting the symmetry selection rules in the
      optical excitation. 

PMID- 23971614
TI  - Flexoelectrically driven electroclinic effect in the twist-bend nematic phase of
      achiral molecules with bent shapes.
AB  - We extend the twist-bend nematic (N(TB)) model to describe the electro-optics of
      this novel phase. We predict an electroclinic effect (ECE) subject to a dc
      electric field E applied perpendicular to the helix axis or wave vector q, with
      rotation of the N(TB) optic axis around E. This linear effect, with its
      flexoelectric origin, is a close analog to the electro-optic effects observed for
      chiral liquid crystals. However, in nematics composed of achiral molecules having
      a bent shape, it is the electro-optic signature of the N(TB) phase. We test our
      model experimentally in the low-temperature nematic phase of the odd liquid
      crystal dimer, CB7CB, with its molecules having, on average, a bent shape. The
      ECE measurements confirm the previously proposed twist-bend nematic structure of
      this phase, with its broken chiral symmetry, extremely short (<10  nm) doubly
      degenerate pitch and ultrafast, submicrosecond response times.

PMID- 23971615
TI  - Locomotion of helical bodies in viscoelastic fluids: enhanced swimming at large
      helical amplitudes.
AB  - The motion of a rotating helical body in a viscoelastic fluid is considered. In
      the case of force-free swimming, the introduction of viscoelasticity can either
      enhance or retard the swimming speed and locomotive efficiency, depending on the
      body geometry, fluid properties, and the body rotation rate. Numerical solutions
      of the Oldroyd-B equations show how previous theoretical predictions break down
      with increasing helical radius or with decreasing filament thickness. Helices of
      large pitch angle show an increase in swimming speed to a local maximum at a
      Deborah number of order unity. The numerical results show how the small-amplitude
      theoretical calculations connect smoothly to the large-amplitude experimental
      measurements. 

PMID- 23971616
TI  - Origin of rigidity in dry granular solids.
AB  - Solids are distinguished from fluids by their ability to resist shear. In
      traditional solids, the resistance to shear is associated with the emergence of
      broken translational symmetry as exhibited by a nonuniform density pattern. In
      this work, we focus on the emergence of shear rigidity in a class of solids where
      this paradigm is challenged. Dry granular materials have no energetically or
      entropically preferred density modulations. We show that, in contrast to
      traditional solids, the emergence of shear rigidity in these granular solids is a
      collective process, which is controlled solely by boundary forces, the
      constraints of force and torque balance, and the positivity of the contact
      forces. We develop a theoretical framework based on these constraints, which
      connects rigidity to broken translational symmetry in the space of forces, not
      positions of grains. We apply our theory to experimentally generated shear-jammed
      states and show that these states are indeed characterized by a persistent, non
      uniform density modulation in force space, which emerges at the shear-jamming
      transition. 

PMID- 23971617
TI  - Strain hardening in startup shear of long-chain branched polymer solutions.
AB  - We show for the first time that entangled polymeric liquids containing long-chain
      branching can exhibit strain hardening upon startup shear. As the significant
      long-chain branching impedes chain disentanglement, Gaussian coils between
      entanglements can deform to reach the finite extensibility limit where the
      intrachain retraction force exceeds the value expected from the usual
      conformational entropy loss evaluated based on Gaussian chain statistics. The
      phenomenon is expected to lead to further theoretical understanding. 

PMID- 23971618
TI  - Anomalous surface relaxations of branched-polymer melts.
AB  - The dynamics of thermally stimulated surface fluctuations of 100 nm thick films
      of long-branched polymers are measured for the first time. In contrast to
      comparable films of linear or cyclic chains that show no change in viscosity upon
      confinement, films of 6-pom, 6-star, and 6-end end-branched stars show
      viscosities, inferred from x-ray photon correlation spectroscopy, as much as 100
      times higher than in the bulk. This difference varies in magnitude with chain
      architecture. Branching has a profound effect on confinement, even for these
      unentangled chains. 

PMID- 23971619
TI  - Nature of the epidemic threshold for the susceptible-infected-susceptible
      dynamics in networks.
AB  - We develop an analytical approach to the susceptible-infected-susceptible
      epidemic model that allows us to unravel the true origin of the absence of an
      epidemic threshold in heterogeneous networks. We find that a delicate balance
      between the number of high degree nodes in the network and the topological
      distance between them dictates the existence or absence of such a threshold. In
      particular, small-world random networks with a degree distribution decaying
      slower than an exponential have a vanishing epidemic threshold in the
      thermodynamic limit. 

PMID- 23971621
TI  - Interface haze associated with topical nonsteroidal anti-inflammatory drug use
      after descemet stripping automated endothelial keratoplasty.
AB  - PURPOSE: To determine if topical nonsteroidal anti-inflammatory drug (NSAID) use
      after Descemet stripping automated endothelial keratoplasty (DSAEK) is associated
      with the development of interface haze. METHODS: A retrospective case-control
      study of patients undergoing DSAEK surgery. RESULTS: Of the 61 patients receiving
      topical NSAIDs, 51% were noted to develop interface haze, and 9% of the control
      group (N=100, no NSAID) developed haze. There was no significant difference in
      best corrected visual acuity between the 2 groups. CONCLUSIONS: Topical NSAID use
      is associated with the development of interface haze, although it may not be
      visually significant and could be related to confounding factors.

PMID- 23971620
TI  - Red blood cell fatty acid analysis for determining compliance with omega3
      supplements in dry eye disease trials.
AB  - PURPOSE: To evaluate pill counts and red blood cell (RBC) membrane fatty acid
      profiles as measures of compliance with oral omega3 polyunsaturated fatty acids
      (omega3 PUFAs) and to compare the two techniques. METHODS: Sixteen dry eye
      disease subjects were given oral omega3 PUFA or placebo for 3 months. Compliance
      was measured by pill counts and blood tests at baseline and 3 months. The
      Wilcoxon signed-rank tests and rank-sum tests were used to compare changes from
      baseline and the difference between the two groups; Spearman correlation
      coefficients were used to assess the relationship of pill counts to changes in
      blood FAs. RESULTS: Pill counts for the omega3 (n=7) and placebo (n=9) groups
      showed a mean consumption of 4.39 and 4.76 pills per day, respectively. In the
      omega3 group, the median change from baseline was +1.46% for eicosapentaenoic
      acid (EPA) (P=0.03), +1.49% for docosahexaenoic acid (DHA) (P=0.08), and -1.91%
      for arachidonic acids (AA) (P=0.02). In the placebo group, median changes in all
      measured FAs were small and not statistically significant. The difference in
      change in FA levels between the two groups was significantly greater for EPA
      (P=0.01) and AA (P=0.04). The correlations between pill counts and changes in EPA
      (r=0.36, P=0.43) and DHA (r=0.17, P=0.70) were not strong. CONCLUSIONS: RBC FA
      analysis can be used to measure compliance in the active group and also monitor
      the placebo group for nonstudy omega3 intake. Low correlation of pill counts with
      blood levels suggests that pill counts alone may be inaccurate and should be
      replaced or supplemented with objective measures.

PMID- 23971622
TI  - Meta-analysis of the effect of intravitreal bevacizumab versus intravitreal
      triamcinolone acetonide in central retinal vein occlusion.
AB  - PURPOSE: To further evaluate the effect of intravitreal bevacizumab (IVB) for the
      treatment of central retinal vein occlusion (CRVO) by meta-analysis. METHODS:
      Pertinent publications were identified through PubMed, EMBASE, and the Cochrane
      Controlled Trials Register up to January 30, 2013. Changes in central macular
      thickness (CMT) and best-corrected visual acuity (BCVA) were extracted at 4, 12,
      and 24 weeks after treatment, and a meta-analysis was carried out to compare
      results between groups receiving IVB and intravitreal triamcinolone acetonide
      (IVTA). RESULTS: One randomized controlled trial and 4 comparative studies were
      identified and included. All of the funnel plots, the Egger's method and Begg
      method did not show publication bias. Our meta-analysis revealed that BCVA and
      CMT at 4, 12, and 24 weeks after treatment did not vary significantly between the
      IVB groups and IVTA groups (BCVA: at 4 weeks, P=0.27; at 12 weeks, P=0.51; at 24
      weeks, P=0.64; CMT at 4 weeks, P=0.88; at 12 weeks, P=0.57; at 24 weeks, P=0.64).
      However, the rate of intraocular pressure rise after intravitreal injection
      varied significantly between the IVB groups and IVTA groups (P<0.001).
      CONCLUSIONS: Our results showed a similar improvement in BCVA and CMT among CRVO
      patients was obtained after intravitreal injections of both IVB, or IVTA, while
      the rate of IOP rise was significantly higher in the latter.

PMID- 23971623
TI  - Phenolic acids from wheat show different absorption profiles in plasma: a model
      experiment with catheterized pigs.
AB  - The concentration and absorption of the nine phenolic acids of wheat were
      measured in a model experiment with catheterized pigs fed whole grain wheat and
      wheat aleurone diets. Six pigs in a repeated crossover design were fitted with
      catheters in the portal vein and mesenteric artery to study the absorption of
      phenolic acids. The difference between the artery and the vein for all phenolic
      acids was small, indicating that the release of phenolic acids in the large
      intestine was not sufficient to create a porto-arterial concentration difference.
      Although, the porto-arterial difference was small, their concentrations in the
      plasma and the absorption profiles differed between cinnamic and benzoic acid
      derivatives. Cinnamic acids derivatives such as ferulic acid and caffeic acid had
      maximum plasma concentration of 82 +/- 20 and 200 +/- 7 nM, respectively, and
      their absorption profiles differed depending on the diet consumed. Benzoic acid
      derivatives showed low concentration in the plasma (<30 nM) and in the diets. The
      exception was p-hydroxybenzoic acid, with a plasma concentration (4 +/- 0.4 MUM),
      much higher than the other plant phenolic acids, likely because it is an
      intermediate in the phenolic acid metabolism. It was concluded that plant
      phenolic acids undergo extensive interconversion in the colon and that their
      absorption profiles reflected their low bioavailability in the plant matrix. 

PMID- 23971624
TI  - Telomere length dynamics in human memory T cells specific for viruses causing
      acute or latent infections.
AB  - BACKGROUND: Declining telomere length (TL) is associated with T cell senescence.
      While TL in naive and memory T cells declines with increasing age, there is
      limited data on TL dynamics in virus-specific memory CD4+ T cells in healthy
      adults. We combined BrdU-labeling of virus-stimulated T cells followed with flow
      cytometry-fluorescent in situ hybridization for TL determination. We analyzed TL
      in T cells specific for several virus infections: non-recurring acute (vaccinia
      virus, VACV), recurring-acute (influenza A virus, IAV), and reactivating viruses
      (varicella-zoster virus, VZV, and cytomegalovirus, CMV) in 10 healthy subjects.
      Additionally, five subjects provided multiple blood samples separated by up to 10
      years. RESULTS: VACV- and CMV-specific T cells had longer average TL than IAV
      specific CD4+ T cells. Although most virus-specific cells were CD45RA-, we
      observed a minor population of BrdU+ CD45RA+ T cells characterized by long
      telomeres. Longitudinal analysis demonstrated a slow decline in average TL in
      virus-specific T cells. However, in one subject, VZV reactivation led to an
      increase in average TL in VZV-specific memory T cells, suggesting a conversion of
      longer TL cells from the naive T cell repertoire. CONCLUSIONS: TLs in memory CD4+
      T cells in otherwise healthy adults are heterogeneous and follow distinct virus
      specific kinetics. These findings suggests that the distribution of TL and the
      creation and maintenance of long TL memory T cells could be important for the
      persistence of long-lived T cell memory.

PMID- 23971625
TI  - Chronic obstructive pulmonary disease and exacerbations: patient insights from
      the global Hidden Depths of COPD survey.
AB  - BACKGROUND: Although chronic obstructive pulmonary disease (COPD) is a major
      global health burden there is a lack of patient awareness of disease severity,
      particularly in relation to exacerbations. METHODS: We conducted a global patient
      survey using an innovative, internet-based methodology to gain insight into
      patient perceptions of COPD and exacerbations in a real-world sample typical of
      today's working-age COPD population. RESULTS: Two thousand patients with COPD
      (53%), chronic bronchitis (52%) and/or emphysema (22%) from 14 countries
      completed an online questionnaire developed by the authors. The Medical Research
      Council (MRC) breathlessness scale was used to delineate symptom severity. Over
      three quarters of patients (77%) had experienced an exacerbation, with 27% of MRC
      1 and 2 patients and 52% of MRC 3, 4 and 5 patients requiring hospitalization as
      a result of an exacerbation. While a majority of MRC 1 and 2 patients (51%)
      reported being back to normal within a few days of an exacerbation, 23% of MRC 3,
      4 and 5 patients took several weeks to return to normal and 6% never fully
      recovered. A high proportion of patients (39%) took a 'wait and see' approach to
      exacerbations.Despite the high prevalence of exacerbations and their negative
      impact on quality of life, 73% of MRC 1 and 2 patients and 64% of MRC 3, 4 and 5
      patients felt that they had control of their COPD. However, 77% of all patients
      were worried about their long-term health, and 38% of MRC 1 and 2 patients and
      59% of MRC 3, 4 and 5 patients feared premature death due to COPD. CONCLUSIONS:
      To reduce the adverse effects of COPD on patients' quality of life and address
      their fears for the future, we need better patient education and improved
      prevention and treatment of exacerbations.

PMID- 23971626
TI  - Long-term follow-up of kidney transplant recipients: comparison of
      hospitalization rates to the general population.
AB  - BACKGROUND: Kidney transplant recipients are recognized as a vulnerable
      population that is at increased risk of adverse health outcomes. However, there
      have been few studies that have compared hospital-related morbidity of these
      patients to the general population, and how this differs with respect to time
      since transplantation. Such analyses are useful in estimating the health burden
      in this patient population. METHODS: We assembled a population-based Canadian
      cohort (excluding Quebec) of 6,116 kidney transplant recipients who underwent
      transplantation between 1 April 2001 and 31 December 2008. Record linkage was
      used to identify hospital discharge records of these patients from 1 April 2001
      through 31 March 2009. Hospital discharges were tabulated across the main disease
      chapters of the ICD10, and person-years of follow-up were calculated across age
      and sex strata. Comparisons of hospital-related morbidity to the general
      population were made by using a standardized hospitalization ratio (SHR). For
      those who underwent transplantation in 2004, stratified analyses were performed
      to explore differences in hospital discharge rates both before and after
      transplantation. RESULTS: After excluding hospitalizations due to complications
      from transplantation, when compared to the general population, transplant
      recipients were approximately 6.4 (95% CI: 6.3, 6.5) times more likely to be
      hospitalized during follow-up. The SHRs were highest during the time periods
      proximate to transplantation, and then decreased to approximately a five-fold
      increase from 3 years post transplantation onwards. The largest disease-specific
      excesses were observed with infectious diseases and diseases of the endocrine
      system. Among those who underwent transplantation in 2004, the SHR decreased from
      11.2 to 5.0 in the periods before and after surgery, respectively. CONCLUSIONS:
      Our results indicate that, even more than 5-years post transplantation, there
      remains a more than six-fold difference in hospitalization rates relative to the
      general population. Additional work is needed to confirm these findings, and to
      develop strategies to reduce long-term morbidity in this patient population.

PMID- 23971627
TI  - Benzodiazepines: electron affinity, receptors and cell signaling - a multifaceted
      approach.
AB  - This report entails a multifaceted approach to benzodiazepine (BZ) action,
      involving electron affinity, receptors, cell signaling and other aspects.
      Computations of the electron affinities (EAs) of different BZs have been carried
      out to establish the effect of various substituents on their EA. These
      computations were undertaken to serve as a first step in determining what role
      electron transfer (ET) plays in BZ activity. The calculations were conducted on
      the premise that the nature of the substituent will either decrease or increase
      the electron density of the benzene ring, thus altering the ability of the
      molecule to accept an electron. Investigations were performed on the effect of
      drug protonation on EA. Similarities involving substituent effects in prior
      electrochemical studies are also discussed. As part of the multifaceted approach,
      EA is linked to ET, which appears to play a role in therapeutic activity and
      toxicity. There is extensive literature dealing with the role of receptors in BZ
      activity. Significant information on receptor involvement was reported more than
      40 years ago. Gamma-aminobutyric acid (GABA) is known to be importantly involved.
      GABA is a probable mediator of BZ effects. BZ and GABA receptors, although not
      identical, are physiologically linked. Cell signaling is known to play a part in
      the biochemistry of BZ action. Various factors participated, such as gene
      expression, allosteric influence, toxic effects and therapeutic action. Evidence
      points to involvement of EA and ET in the mode of action in cell signaling.
      Oxidative stress and antioxidant effects are also addressed.

PMID- 23971628
TI  - Association of angiotensin II type-1 receptor A1166C gene polymorphism with the
      susceptibility of end-stage renal disease.
AB  - Association between angiotensin II type-1 receptor (AT1R) A1166C gene
      polymorphism and end-stage renal disease (ESRD) risk is still controversial. This
      meta-analysis was performed to evaluate the association of AT1R A1166C gene
      polymorphism with ESRD susceptibility. The search was performed in the databases
      of PubMed, Embase and Cochrane Library as of 1 May 2012, and the eligible
      investigations were recruited for this meta-analysis. Nineteen literatures were
      identified for the analysis of association between AT1R A1166C gene polymorphism
      and ESRD susceptibility. There was no association between AT1R A1166C gene
      polymorphism and ESRD susceptibility for overall populations, Caucasians, Asians
      and Turkish population. Interestingly, CC genotype was associated with a higher
      risk of ESRD in Africans (OR = 3.36, 95% CI: 1.42-7.99, p = 0.006). However, C
      allele and AA genotype were not associated with the ESRD risk in African
      population. In conclusion, CC genotype might be a risk factor for the ESRD
      susceptibility in African population. However, more case-control association
      investigations on larger, stratified populations are required in the future.

PMID- 23971629
TI  - Adiponectin receptors are present in RANK-L-induced multinucleated osteoclast
      like cells.
AB  - Adiponectin is an adipokine that has been related to bone metabolism. Data on
      adiponectin receptors (AdipoR1, -R2) in osteoclasts have shown discrepancies. In
      this study we carried out observations of AdipoR1, -R2 in peripheral blood
      mononuclear cells that were induced to differentiate into osteoclasts. AdipoR1, 
      R2 were screened using reverse transcription and quantitative PCR and
      immunofluorescence. Acid phosphatase and Cathepsin-K were evaluated as
      osteoclastic markers. Results showed that acid phosphatase was expressed from day
      1 whereas Cathepsin-K started from day 7. AdipoR1 and -R2 showed expression from
      day 1, with greater expression for AdipoR1 than AdipoR2. The immunofluorescent
      patterns were observed in the cells cultured under three different conditions:
      non-supplemented medium, added M-CSF, or medium with M-CSF, and RANK-L. The non
      supplemented control did not display specific fluorescence whereas specific and
      strong signals were detected in cells cultured with combined M-CSF and RANK-L
      from day 7. The fluorescence patterns were detected mainly at the periphery of
      the cells, and in the cytoplasm, showing a localized patchy pattern for both
      receptors. In contrast, a diffuse fluorescent pattern was detected in the
      cytoplasm of the cells with M-CSF alone. In summary, AdipoR1 and -R2 were
      detected by quantitative PCR and immunofluorescence. The immunofluorescence
      patterns suggest that adiponectin receptors are located, or re-located, in the
      plasma membrane with distribution in the cytoplasm when mononuclear cells are
      committed to differentiate to osteoclasts. These findings could be a reasonable
      explanation for the controversy found in the published literature regarding the
      role of adiponectin in bone metabolism.

PMID- 23971630
TI  - The signaling pathway of hypoxia inducible factor and its role in renal diseases.
AB  - It is well-documented that hypoxia inducible factor (HIF) is a key mediator of
      tissue and cellular adaptation to hypoxia. HIF-target genes are also involved in
      cellular apoptosis and profibrotic mechanisms. The role of HIF in diseases is not
      consistent. It is a risk factor for tumor progression, whereas it plays a
      protective role against ischemic hypofusion. For renal diseases, it is not always
      a risk or protective factor. Many factors are involved in the pathogenesis of
      renal diseases. It is reported that HIF not only increases hypoxia tolerance, but
      also regulates a lot of signaling pathways. In the past decades, a number of
      studies were also conducted to explore the association between HIF and the risk
      of renal diseases. However, the role of HIF in the development of renal diseases
      was not entirely clear. In this study, the signal transduction pathways of HIF
      and its role in the pathogenesis of renal diseases were reviewed.

PMID- 23971631
TI  - Light scattering and extinction measurements combined with laser-induced
      incandescence for the real-time determination of soot mass absorption cross
      section.
AB  - An aerosol albedometer was combined with laser-induced incandescence (LII) to
      achieve simultaneous measurements of aerosol scattering, extinction coefficient,
      and soot mass concentration. Frequency doubling of a Nd:YAG laser line resulted
      in a colinear beam of both lambda = 532 and 1064 nm. The green beam was used to
      perform cavity ring-down spectroscopy (CRDS), with simultaneous measurements of
      scattering coefficient made through use of a reciprocal sphere nephelometer. The
      1064 nm beam was selected and directed into a second integrating sphere and used
      for LII of light-absorbing kerosene lamp soot. Thermal denuder experiments showed
      the LII signals were not affected by the particle mixing state when laser peak
      power was 1.5-2.5 MW. The combined measurements of optical properties and soot
      mass concentration allowed determination of mass absorption cross section
      (M.A.C., m(2)/g) with 1 min time resolution when soot concentrations were in the
      low microgram per cubic meter range. Fresh kerosene nanosphere soot (ns-soot)
      exhibited a mean M.A.C and standard deviation of 9.3 +/- 2.7 m(2)/g while limited
      measurements on dry ambient aerosol yielded an average of 8.2 +/- 5.9 m(2)/g when
      soot was >0.25 MUg/m(3). The method also detected increases in M.A.C. values
      associated with enhanced light absorption when polydisperse, laboratory-generated
      ns-soot particles were embedded within or coated with ammonium nitrate, ammonium
      sulfate, and glycerol. Glycerol coatings produced the largest fractional increase
      in M.A.C. (1.41-fold increase), while solid coatings of ammonium sulfate and
      ammonium nitrate produced increases of 1.10 and 1.06, respectively. Fresh, ns
      soot did not exhibit increased M.A.C. at high relative humidity (RH); however,
      lab-generated soot coated with ammonium nitrate and held at 85% RH exhibited
      M.A.C. values nearly double the low-humidity case. The hybrid instrument for
      simultaneously tracking soot mass concentration and aerosol optical properties in
      real time is a valuable tool for probing enhanced absorption by soot at
      atmospherically relevant concentrations. 

PMID- 23971632
TI  - Fluorescent proteins in cellular organelles: serious pitfalls and some solutions.
AB  - Fluorescent proteins (FPs) have been powerful tools for cell biologists for over
      15 years. The large variety of FPs available rarely comes with an instruction
      manual or a warning label. The potential pitfalls of the use of FPs in cellular
      organelles represent a significant concern for investigators. FPs generally did
      not evolve in the often distinctive physicochemical environments of subcellular
      organelles. In organelles, FPs can misfold, go dark, and even distort organelle
      morphology. In this minireview, we describe the issues associated with FPs in
      organelles and provide solutions to enable investigators to better exploit FP
      technology in cells. 

PMID- 23971633
TI  - Resection of supratentorial lobar cavernous malformations in children: clinical
      article..
AB  - OBJECT: The authors present a series of children with supratentorial lobar
      cavernous malformations (CMs). Current imaging and operative techniques along
      with long-term follow-up were incorporated to characterize the response to
      surgical treatment in this pediatric population. METHODS: The senior author's
      operative experience was reviewed retrospectively along with a review of the
      Boston Children's Hospital database from 1997 to 2011 for children with
      supratentorial lobar CMs. Lobar CM was defined as having a supratentorial
      location but not involving the thalamus/hypothalamus or basal ganglia. Baseline
      patient demographics, pertinent radiographic findings, operative outcomes, and
      long-term results were evaluated and compared between patients managed
      operatively and those who were managed nonoperatively. RESULTS: Of 238 CMs
      identified, 181 (76%) were lobar. Compared with patients managed with observation
      only, those selected for surgery were older (p = 0.03), more likely to have
      symptomatic lesions (p < 0.001), and had larger lesions (p < 0.001). Of the 83
      CMs selected for surgery, 98% were completely resected. Over a total of 384.5
      patient-years of follow-up after surgery (mean 4.6 years; median 2.7 years; range
      0.1-22.3 years), there were no subsequent hemorrhages in any patient undergoing
      complete resection; 1 of the 2 incompletely resected lesions rebled during the
      follow-up period. Radiographically, there was 1 recurrence (1.2%) in a child with
      multiple CMs; there were no recurrences of completely resected single lesions. Of
      the 48 patients who presented with seizures (acute or chronic), 46 (96%) were
      seizure free at follow-up. The permanent neurological complication rate of
      surgery was 5%; these complications were limited to those patients whose lesions
      were in eloquent locations. CONCLUSIONS: Pediatric patients with symptomatic
      supratentorial lobar CMs are ideal candidates for surgery, for which there are
      high complete resection rates, rewarding long-term seizure outcomes, and low
      operative morbidity. Observation may be warranted in smaller asymptomatic lesions
      located within eloquent cortex.

PMID- 23971634
TI  - Low-dose head computed tomography in children: a single institutional experience
      in pediatric radiation risk reduction: clinical article.
AB  - OBJECT: In this study, the authors describe their experience with a low-dose head
      CT protocol for a preselected neurosurgical population at a dedicated pediatric
      hospital (Seattle Children's Hospital), the largest number of patients with this
      protocol reported to date. METHODS: All low-dose head CT scans between October
      2011 and November 2012 were reviewed. Two different low-dose radiation dosages
      were used, at one-half or one-quarter the dose of a standard head CT scan, based
      on patient characteristics agreed upon by the neurosurgery and radiology
      departments. Patient information was also recorded, including diagnosis and
      indication for CT scan. RESULTS: Six hundred twenty-four low-dose head CT
      procedures were performed within the 12-month study period. Although indications
      for the CT scans varied, the most common reason was to evaluate the ventricles
      and catheter placement in hydrocephalic patients with shunts (70%), followed by
      postoperative craniosynostosis imaging (12%). These scans provided adequate
      diagnostic imaging, and no patient required a follow-up full-dose CT scan as a
      result of poor image quality on a low-dose CT scan. Overall physician comfort and
      satisfaction with interpretation of the images was high. An additional 2150 full
      dose head CT scans were performed during the same 12-month time period, making
      the total number of CT scans 2774. This value compares to 3730 full-dose head CT
      scans obtained during the year prior to the study when low-dose CT and rapid
      sequence MRI was not a reliable option at Seattle Children's Hospital. Thus, over
      a 1-year period, 22% of the total CT scans were able to be converted to low-dose
      scans, and full-dose CT scans were able to be reduced by 42%. CONCLUSIONS: The
      implementation of a low-dose head CT protocol substantially reduced the amount of
      ionizing radiation exposure in a preselected population of pediatric
      neurosurgical patients. Image quality and diagnostic utility were not
      significantly compromised.

PMID- 23971636
TI  - Surgical treatment of refractory status epilepticus in children: clinical
      article.
AB  - OBJECT: Refractory status epilepticus (RSE) is a life-threatening neurological
      emergency associated with high morbidity and mortality. Affected patients often
      require prolonged intensive care and can suffer multiple complications. Surgical
      intervention to control RSE is rarely used but can obviate the risks of prolonged
      seizures and intensive care treatment. Authors of the present study analyzed
      their experience with the surgical management of patients suffering from RSE.
      METHODS: The Epilepsy Surgery Database at Miami Children's Hospital was reviewed
      for patients who had undergone surgery for RSE. Clinical presentation,
      electrophysiological profile, radiological data, surgical details, and
      postoperative course were evaluated. RESULTS: Between 1990 and 2012, 15 patients
      underwent surgery for uncontrolled seizures despite high-dose medical suppressive
      therapy. The mean preoperative duration of status epilepticus was 8 weeks. Ictal
      SPECT and FDG-PET imaging in conjunction with intraoperative electrophysiological
      studies helped to outline the extent of resection. Surgical intervention
      controlled seizures in all patients and facilitated the transition out of
      intensive care. Adverse events related to a prolonged intensive care unit stay
      included sepsis and respiratory complications. Four patients had worsened
      neurological function, developing hemiparesis and dysphasia. There was no
      operative mortality. CONCLUSIONS: Surgical intervention can successfully control
      refractory partial status epilepticus, prevent associated morbidity, and decrease
      intensive care unit stay. Ictal SPECT and PET are valuable in guiding resection.

PMID- 23971637
TI  - Autosomal dominant polycystic kidney disease: cardiovascular complications.

PMID- 23971635
TI  - Amniotic fluid and serum biomarkers from women with neural tube defect-affected
      pregnancies: a case study for myelomeningocele and anencephaly: clinical article.
AB  - OBJECT: The authors sought to identify novel biomarkers for early detection of
      neural tube defects (NTDs) in human fetuses. METHODS: Amniotic fluid and serum
      were drawn from women in the second trimester of pregnancy. The study group
      included 2 women pregnant with normal fetuses and 4 with fetuses displaying
      myelomeningocele (n = 1), anencephaly (n = 1), holoprosencephaly (n = 1), or
      encephalocele (n = 1). Amniotic fluid stem cells (AFSCs) were isolated and
      cultured. The cells were immunostained for the stem cell markers Oct4, CD133, and
      Sox2; the epigenetic biomarkers H3K4me2, H3K4me3, H3K27me2, H3K27me3, H3K9Ac, and
      H3K18Ac; and the histone modifiers KDM6B (a histone H3K27 demethylase) and Gcn5
      (a histone acetyltransferase). The levels of 2 markers for neural tube
      development, bone morphogenetic protein-4 (BMP4) and sonic hedgehog (Shh), were
      measured in amniotic fluid and serum using an enzyme-linked immunosorbent assay.
      RESULTS: The AFSCs from the woman pregnant with a fetus affected by
      myelomeningocele had higher levels of H3K4me2, H3K4me3, H3K27me2, and H3K27me3
      and lower levels of KDM6B than the AFSCs from the women with healthy fetuses. The
      levels of H3K9ac, H3K18ac, and Gcn5 were also decreased in the woman with the
      fetus exhibiting myelomeningocele. In AFSCs from the woman carrying an
      anencephalic fetus, levels of H3K27me3, along with those of H3K9Ac, H3K18ac, and
      Gcn5, were increased, while that of KDM6B was decreased. Compared with the normal
      controls, the levels of BMP4 in amniotic fluid and serum from the woman with a
      fetus with myelomeningocele were increased, whereas levels of Shh were increased
      in the woman pregnant with a fetus displaying anencephaly. CONCLUSIONS: The
      levels of epigenetic marks, such as H3K4me, H3K27me3, H3K9Ac, and H3K18A, in
      cultured AFSCs in combination with levels of key developmental proteins, such as
      BMP4 and Shh, are potential biomarkers for early detection and identification of
      NTDs in amniotic fluid and maternal serum.

PMID- 23971638
TI  - Cardiovascular complications in autosomal dominant polycystic kidney disease.
AB  - Cardiovascular complications are a major cause of morbidity and mortality in
      patients with autosomal dominant polycystic kidney disease (ADPKD). Hypertension
      is a common finding of ADPKD occurring in 50-70% of patients before the
      impairment of renal function. Stimulation of the renin-angiotensin-aldosterone
      system plays a major role in the development of hypertension in ADPKD.
      Hypertension is associated with an increased rate of progression to end-stage
      renal disease and is the most important potentially treatable variable in these
      patients. Left ventricular hypertrophy, a major cardiovascular risk factor, is
      also common in patients with ADPKD. Both hypertension and left ventricular
      hypertrophy play a crucial role in the development of cardiovascular
      complications in these patients. Furthermore, endothelial dysfunction, impaired
      coronary flow velocity reserve, biventricular diastolic dysfunction, increased
      carotid intima-media thickness, and arterial stiffness are present even in young
      normotensive patients with ADPKD who have well-preserved renal function. These
      findings suggest that cardiovascular involvement starts very early in the course
      of ADPKD. Intracranial and extracranial aneurysms and cardiac valvular defects
      are other potential cardiovascular problems in patients with ADPKD. A
      multifactorial approach aiming at all cardiovascular risk factors, such as
      hypertension, smoking, dyslipidemia and obesity is extremely important in these
      patients. Early diagnosis and treatment of hypertension, with drugs that block
      the renin-angiotensin-aldosterone system, has the potential to decrease the
      cardiovascular complications and slow the progression of renal disease in ADPKD. 

PMID- 23971639
TI  - Renin-Angiotensin-aldosterone system in autosomal dominant polycystic kidney
      disease.
AB  - Autosomal dominant polycystic kidney disease is the most frequent life
      threatening hereditary disease. Prognostic factors for progressive renal
      impairment have been identified such as gender, race, age, proteinuria,
      hematuria, hypertension. Hypertension is the only risk factor for renal
      dysfunction in autosomal dominant polycystic kidney disease, which is presently
      treatable. Better understanding of the pathophysiology of hypertension will help
      in defining appropriate interventions. The renin-angiotensin-aldosterone-system
      is the pivotal factor in the pathogenesis of hypertension in autosomal dominant
      polycystic kidney disease. Basic research and clinical studies in autosomal
      dominant polycystic kidney disease implicated activation of the renin-angiotensin
      aldosterone-system. Therapy of hypertension in autosomal dominant polycystic
      kidney disease with angiotensin-converting enzyme inhibitors or angiotensin
      receptor blocker has the potential to prevent cardiovascular complications and
      slow the progression of renal disease. The results of two large multicenter
      double-blind placebo controlled randomized clinical trials (the HALT-PKD trials)
      possibly will elucidate the beneficial effects of the renin-angiotensin
      aldosterone-system inhibition in autosomal dominant polycystic kidney disease. 

PMID- 23971640
TI  - Hypertension in children with autosomal dominant polycystic kidney disease
      (ADPKD).
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common
      hereditary renal disease, affecting 1 in 1000 individuals. Previously termed
      "adult polycystic kidney disease", ADPKD is now known to have important clinical
      manifestations beginning early in life and even in utero. Hypertension is an
      important risk factor for progressive renal and cardiovascular disease in
      children with ADPKD and may signify irremediable organ injury. The purpose of
      this article is to review current knowledge and treatment strategies in
      hypertension associated with pediatric ADPKD. 

PMID- 23971641
TI  - Left ventricular hypertrophy in ADPKD: changing demographics.
AB  - Left ventricular hypertrophy (LVH) has been recognized as an early and important
      complication in patients with autosomal dominant polycystic kidney disease
      (ADPKD). LVH is associated with arrhythmias, congestive heart failure, and
      increased cardiac mortality. The increase in left ventricular mass is attributed
      to the compensatory myocardial remodeling associated with systemic hypertension,
      which is also highly prevalent in those with ADPKD. Several observational studies
      over the past decades using echocardiography have estimated the prevalence of LVH
      in adults to range from 20-40%. More recently, the HALT-PKD study detected an LVH
      prevalence of less than 4% using magnetic resonance imaging. Some of the
      differences may relate to the imaging modality, variations in parameters used to
      define LVH, or demographic differences in the study populations. Nonetheless,
      there likely exists a shift in the pathophysiology of LVH in patients with ADPKD.
      Factors that explain this evolving trend include earlier detection and treatment
      of hypertension, more rigorous blood pressure control, and an increased use of
      renin-angiotensin-aldosterone system (RAAS) antagonists. The use of RAAS
      inhibitors has been shown to induce regression of LVH, and this may continue to
      play an important role in the cardiovascular risk management in patients with
      ADPKD. The results of ongoing studies will help elucidate these relationships. 

PMID- 23971642
TI  - Endothelial dysfunction and angiogenesis in autosomal dominant polycystic kidney
      disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common
      potentially lethal hereditary disease. The hall mark of the disease is the
      development of innumerable cysts in kidneys and liver. However, a vascular
      phenotype including the early occurrence of hypertension, abnormalities in renal
      blood flow, intracranial and aortic aneurysms, spontaneous coronary and
      cervicocephalic artery dissections, and dolichoectasias of intracranial arteries
      is also part of the spectrum of ADPKD. While endothelial dysfunction occurs early
      in ADPKD and precedes the onset of hypertension, the pathogenesis of endothelial
      dysfunction has not been extensively studied. Development of endothelial
      dysfunction in ADPKD (as in other conditions characterized by endothelial
      dysfunction) has been linked to oxidative stress and vascular inflammation.
      Vascular dysfunction with increased contraction and decreased relaxation causes
      downstream tissue ischemia, a potent stimulus for angiogenesis. Evidence of
      angiogenesis on the surface of renal cysts has been documented in human ADPKD. In
      addition, high levels of angiogenic growth factors including vascular endothelial
      growth factor have been reported in cyst fluid and in the circulation of patients
      with ADPKD. In the following chapter we summarize recent studies examining the
      role and pathogenesis of endothelial dysfunction and neoangiogenesis in ADPKD. 

PMID- 23971643
TI  - The genetics of vascular complications in autosomal dominant polycystic kidney
      disease (ADPKD).
AB  - The most important extra-renal manifestation of autosomal dominant polycystic
      kidney disease (ADPKD) in terms of debilitating injury and premature death is the
      development of intracranial aneurysms (IAs) and other vascular complications,
      resulting in subarachnoid hemorrhage (SAH). IAs are found at a rate approximately
      five times higher in ADPKD patients than in the general population and in
      patients with a family history of SAH/IAs the frequency is elevated further three
      to five times, indicating the importance of genetic factors in its etiology.
      Expression of the ADPKD gene products, polycystin-1 (PKD1) and polycystin-2
      (PKD2), in vascular smooth muscle and the endothelium, and evidence that reduced
      levels of these proteins leads to IA development in mouse models, suggests a
      direct role of these proteins in the vascular disease. PKD1 and PKD2 patients
      seem equally likely to develop IAs, while patients with mutations to the 5' half
      of PKD1 may more likely have vascular complications. Genome wide association and
      candidate studies of multiplex families with IAs without ADPKD have identified a
      number of genes/proteins that may be risk factors for the development of IAs.
      These candidate proteins largely have roles in the maintenance and remodeling of
      the arterial wall of small brain arteries. The development of the genetic
      methodologies of massively parallel sequencing mean it is now possible to test
      these and other candidates in ADPKD families with multiplex and singleton IA
      cases. Identifying strong modifiers of this phenotype will be important for
      prioritizing patients for presymptomatic screening and interventions. 

PMID- 23971645
TI  - Does brachial blood pressure need to predict cardiovascular outcomes in end stage
      renal disease? An update.
AB  - Hypertension is responsible for a significantly increased burden of
      cardiovascular events and it is cause and a consequence of Chronic Kidney Disease
      (CKD) and a determinant factor in its progression to End Stage Kidney Disease
      (ESKD). Therefore, nephrologists have been focusing their attention on
      hypertension control to prevent CKD progression, delaying it but with poor
      results on cardiovascular mortality reduction. An important effect is the
      difficulty to adequately reduce BP levels in CKD patients and especially in
      dialysis patients despite the polipharmacological therapy. We have to take into
      account other aspects influencing mortality risk in CKD patients .The first
      aspect to consider is whether brachial blood pressure (BP) measurement is
      sufficient to describe the complex relationship between the alteration of BP and
      outcomes in renal subjects. The second aspect to consider is the variability of
      BP (BPV). We think that BP measurement cannot only take into account brachial BP,
      because it represents a limited measure of a complex clinical condition in CKD or
      ESRD patients. The inability to evaluate hypertension in its complexity explains
      why several aspects are still unrecognized. 

PMID- 23971646
TI  - The role of the immune system in the pathogenesis of hypertension.
AB  - The role of innate and adaptive immunity in the pathogenesis of hypertension has
      received increasing recognition over the past few years. This review will focus
      on recent developments in this emerging area. In particular, the role of
      macrophages and lymphocytes will be highlighted. 

PMID- 23971644
TI  - Experimental therapies and ongoing clinical trials to slow down progression of
      ADPKD.
AB  - The improvement of imaging techniques over the years has contributed to the
      understanding of the natural history of autosomal dominant polycystic kidney
      disease, and facilitated the observation of its structural progression. Advances
      in molecular biology and genetics have made possible a greater understanding of
      the genetics, molecular, and cellular pathophysiologic mechanisms responsible for
      its development and have laid the foundation for the development of potential new
      therapies. Therapies targeting genetic mechanisms in ADPKD have inherent
      limitations. As a result, most experimental therapies at the present time are
      aimed at delaying the growth of the cysts and associated interstitial
      inflammation and fibrosis by targeting tubular epithelial cell proliferation and
      fluid secretion by the cystic epithelium. Several interventions affecting many of
      the signaling pathways disrupted in ADPKD have been effective in animal models
      and some are currently being tested in clinical trials. 

PMID- 23971647
TI  - Acidophilic halophilic microorganisms in fluid inclusions in halite from Lake
      Magic, Western Australia.
AB  - Lake Magic is one of the most extreme of hundreds of ephemeral acid-saline lakes
      in southern Western Australia. It has pH as low as 1.7, salinity as high as 32%
      total dissolved solids, temperatures ranging from 0 degrees C to 50 degrees C,
      and an unusually complex aqueous composition. Optical petrography, UV-vis
      petrography, and laser Raman spectrometry were used to detect microorganisms and
      organic compounds within primary fluid inclusions in modern bedded halite from
      Lake Magic. Rare prokaryotes appear as 1-3 MUm, bright cocci that fluoresce green
      with UV-vis illumination. Dimpled, 5-7 MUm yellow spherules that fluoresce blue
      with UV-vis illumination are interpreted as Dunaliella algae. Yellow-orange beta
      carotene crystals, globules, and coatings are characterized by orange-red
      fluorescence and three distinct Raman peaks. Because acid saline lakes are good
      Mars analogues, the documentation of prokaryotes, eukaryotes, and organic
      compounds preserved in the halite here has implications for the search for life
      on Mars. Missions to Mars should incorporate such in situ optical and chemical
      examination of martian evaporites for possible microorganisms and/or organic
      compounds in fluid inclusions.

PMID- 23971648
TI  - Re: Compalati E, Canonica GW. Efficacy and safety of rupatadine for allergic
      rhino-conjunctivitis: a systematic review of randomized, double-blind, placebo
      controlled studies with meta-analysis. Letter to the editor.

PMID- 23971649
TI  - A patient with Creutzfeldt-Jakob disease presenting with amyotrophy: a case
      report.
AB  - INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is an ultimately fatal,
      neurodegenerative disease caused by misfolded prion protein aggregation and
      accumulation. The development of amyotrophic features has been described in CJD,
      though rarely as an early or prominent feature. Consequently, the significance of
      amyotrophy in prion disease etiology remains unclear. CASE PRESENTATION: Our
      patient, a healthy 70-year-old French/Algerian man, presented to our hospital
      following a work-related fall and was admitted with lower limb skeletal muscle
      atrophy and fasciculations; the fasciculations progressed to involve the trunk,
      upper limbs and face. Within days, he developed evidence of a progressive
      ascending neurological syndrome and subsequent brain involvement with
      supranuclear palsy of upgaze, catalepsy and death 36 days after symptom onset.
      Amyotrophy remained the principle feature of his disease. Dementia started to
      develop within 10 days of the onset of his amyotrophy. Prion disease was
      confirmed at postmortem. CONCLUSIONS: Our observations suggest an unusual form of
      prion disease with prominent early involvement of anterior horn cells, ascending
      prion propagation in the central nervous system and a grave prognosis.

PMID- 23971650
TI  - Psychological resilience: the impact of affectivity and coping on state anxiety
      and positive emotions during and after the Washington, DC sniper killings.
AB  - This research examined the impact of affectivity and coping on state anxiety and
      positive emotions among young adults living in the Washington, DC metro area both
      during and after the Washington, DC sniper killings. Participants completed
      questionnaires during three waves of data collection: (1) during the sniper
      attacks (n=92); (2) within two weeks after the snipers were captured (n=45); and
      (3) six months later (n=43). Affectivity (measured by neuroticism) was
      significantly associated with state anxiety and positive emotions during all
      three time periods. Coping (measured by constructive thinking) predicted state
      anxiety and positive emotions during the shootings, but was unrelated to either
      outcome immediately after the attacks, and marginally related to them six months
      later. Consistent with the Dynamic Model of Affect, state anxiety and positive
      emotions were more strongly (and negatively) correlated with each other during
      the killings than they were after the snipers were apprehended. Taken together,
      these results support transactional models of stress that emphasize the
      interaction between dispositional and situational influences, and they suggest
      that affectivity reflects a fundamental set of reactions to one's environment,
      while coping dispositions result in more stress-specific responses. Additional
      theoretical and practical implications of these findings are also discussed. 

PMID- 23971652
TI  - Ugi multicomponent reaction product: the inhibitive effect on DNA oxidation
      depends upon the isocyanide moiety.
AB  - The hydroxyl-substituted benzoic acid (as phenyl group A in the product), aniline
      (as phenyl group B in the product), benzaldehyde (as phenyl group C in the
      product), and four isocyanides are employed to synthesize bis-amide via an Ugi
      four-component reaction. The effects of the obtained 20 bis-amides on quenching
      radicals and inhibiting DNA oxidation are estimated. It is found that the
      antioxidant effectiveness of bis-amide generated by hydroxyl groups is markedly
      influenced by the structural feature derived from isocyanide. The phenolic
      hydroxyl group attaching to phenyl group A plays a major role in scavenging
      radicals, and the radical-scavenging property is reinforced by the structural
      moiety introduced from ferrocenylmethyl isocyanide. The same conclusion is also
      obtained when bis-amides are used to inhibit DNA oxidation. It is still found
      that the ferrocenylmethyl moiety enhances the antioxidant effect of hydroxyl
      group at phenyl group A in protecting DNA against the oxidation. Moreover, when
      the bis-amide is prepared by the same isocyanide, e.g. ethyl isocyanoacetate, it
      is found that the hydroxyl group at phenyl group C plays the major role in
      inhibiting DNA oxidation, followed by the hydroxyl groups attaching to phenyl
      groups B and A. 

PMID- 23971653
TI  - Metabolomic approach assisted high resolution LC-ESI-MS based identification of a
      xenobiotic derivative of fenhexamid produced by Lactobacillus casei.
AB  - Fenhexamid is a widely used fungicide with one of the highest maximum tolerance
      limits approved for fruits and vegetables. The goal of this study was to examine
      if fenhexamid is metabolized by a nontarget organism, a Lactobacillus species
      (Lactobacillus casei Shirota), a probiotic strain of the human gastrointestinal
      tract. The assignment of bacterial derivatives of the xenobiotic fenhexamid was
      substantially facilitated by a metabolomic software based approach optimized for
      the extraction of molecular features of chlorine-containing compounds from liquid
      chromatography-electrospray ionization-quadrupole time-of-flight mass
      spectrometry data with an untargeted compound search algorithm. After validating
      the software with a set of seventeen chlorinated pesticides and manually
      verifying the result lists, eleven molecular features out of 4363 turned out to
      be bacterial derivatives of fenhexamid, revealing the O-glycosyl derivative as
      the most abundant one that arose from the fermentation medium of Lactobacillus
      casei Shirota in the presence of 100 MUg/mL fenhexamid. 

PMID- 23971651
TI  - Allosterically tunable, DNA-based switches triggered by heavy metals.
AB  - Here we demonstrate the rational design of allosterically controllable, metal-ion
      triggered molecular switches. Specifically, we designed DNA sequences that adopt
      two low energy conformations, one of which does not bind to the target ion and
      the other of which contains mismatch sites serving as specific recognition
      elements for mercury(II) or silver(I) ions. Both switches contain multiple metal
      binding sites and thus exhibit homotropic allosteric (cooperative) responses. As
      heterotropic allosteric effectors we employ single-stranded DNA sequences that
      either stabilize or destabilize the nonbinding state, enabling dynamic range
      tuning over several orders of magnitude. The ability to rationally introduce
      these effects into target-responsive switches could be of value in improving the
      functionality of DNA-based nanomachines. 

PMID- 23971654
TI  - Prevalence of hepatitis B and C in Spain - further data are needed.

PMID- 23971655
TI  - Prevalence of viral hepatitis (B and C) serological markers in healthy working
      population.
AB  - INTRODUCTION AND OBJECTIVES: prevalence of viral hepatitis (B and C) changes
      geographically. Our aim was to determinate the prevalence of hepatitis B (HBV)
      and hepatitis C virus (HCV) serological markers in healthy working population and
      to describe the epidemiological characteristics associated to its presence.
      METHODS: blood samples and epidemiological data of 5,017 healthy workers from
      Murcia and Madrid were recorded prospectively. RESULTS: a total of 5,017 healthy
      volunteers participated. Mean age 39 +/- 11 years, men predominance (73 %).
      Prevalence of serological markers of HCV and HBV was 0.6 % and 0.7 %. Age of
      patients with HCV antibody was significantly higher (43 + or - 9 years vs. 39 +
      or - 11 years; p = 0.03). We observed significant differences in liver test
      values (alanine aminotransferase [ALT] 64 +/- 56 IU/L vs. 28 +/- 20 IU/L; p <
      0.001; aspartate aminotransferase [AST] (51 + or - 45 IU/L vs. 23 + or - 12 IU/L;
      p < 0.001) and in gamma-glutamyltransferase(GGT) value (104 + or - 122 IU/L vs.
      37 + or - 46 IU/L; p < 0.001. The presence of HCV antibody was related
      significantly to previous transfusion (13 % vs. 5 %; p = 0.03), tattoos (29 % vs.
      13 %; p < 0.01), intravenous drug addiction (13 % vs. 0.2 %; p < 0.001) and
      coexistence with people with positive HCV antibody (16 % vs. 4 %; p < 0.001). In
      HBV no differences in basal characteristics were observed with exception in AST
      values (29 + or - 15 IU/L vs. 23 + or - 12 IU/L; p < 0.01). Hepatitis B surface
      antigen (HBsAg) was related significantly to previous transfusion (15 % vs. 5 %;
      p < 0.01), tattoos (26 % vs. 14 %; p = 0.04) and coexistence with people with
      positive HBsAg (17 % vs. 4 %; p < 0.001). CONCLUSIONS: Prevalence of serological
      markers in healthy working population is low. Risk factors for infection were
      previous transfusion and tattoos. Intravenous drug addiction was only a risk
      factor in HCV.

PMID- 23971656
TI  - Quality of life assessment by applying EORTC questionnaires to rectal cancer
      patients after surgery and neoadjuvant and adjuvant treatment.
AB  - BACKGROUND: Quality of Life (QoL) is a key element in rectal cancer (RC)
      patients. AIMS: this study assesses QoL in a sample of RC patients in their
      treatment follow-up period, and compares surgery modalities. PATIENTS AND
      METHODS: eighty four locally advanced RC patients who had received surgery and
      neoadjuvant chemoradiotherapy were included in the study. Of these, 70 had
      adjuvant chemotherapy. All patients completed the EORTC QLQ-C30 and the QLQ-CR29
      once at least one year after completion of their treatment. Low anterior
      resection (LAR) patients also completed a Functional Evaluation questionnaire.
      RESULTS: QoL scores in the EORTC questionnaires for the sample as a whole were
      high in most dimensions, in line with the general population's QoL values,
      although moderate limitations (> 30 points)were observed in urinary frequency,
      flatulence, impotence and sexual function. The scores for the Functional
      Evaluation were adequate (mean combined bowel function score of 18.2). LAR
      patients had a higher stool frequency than those with abdominoperineal resection
      (APR; p < 0.001). No differences in body image were found amongst LAR and APR
      patients. LAR patients with a lower anastomosis had higher faecal incontinence (p
      = 0.02), whereas those with a reservoir had better emotional functioning (p =
      0.04) and higher faecal incontinence (p = 0.03). CONCLUSIONS: QoL scores and
      functional evaluation indicated patients had adapted to their disease and
      treatment. The few differences in QoL found between surgery modalities are in
      line with other recent studies and in contrast with earlier ones that suggested a
      lower QoL in APR patients.

PMID- 23971657
TI  - Development of quality standards in inflammatory bowel disease management and
      design of an evaluation tool of nursing care.
AB  - BACKGROUND AND AIMS: nursing management of inflammatory bowel disease (IBD) is
      highly relevant for patient care and outcomes. However, there is evidence of
      substantial variability in clinical practices. The objectives of this study were
      to develop standards of healthcare quality for nursing management of IBD and
      elaborate the evaluation tool "Nursing Care Quality in IBD Assessment" (NCQ-IBD)
      based on these standards. METHODS: a 178-item healthcare quality questionnaire
      was developed based on a systematic review of IBD nursing management literature.
      The questionnaire was used to perform two 2-round Delphi studies: Delphi A
      included 27 IBD healthcare professionals and Delphi B involved 12 patients. The
      NCQ-IBD was developed from the list of items resulting from both Delphi studies
      combined with the Scientific Committee's expert opinion. RESULTS: the final NCQ
      IBD consists of 90 items, organized in13 sections measuring the following aspects
      of nursing management of IBD: infrastructure, services, human resources, type of
      organization, nursing responsibilities, nurse-provided information to the
      patient, nurses training, annual audits of nursing activities, and nursing
      research in IBD. Using the NCQ-IBD to evaluate these components allows the rating
      of healthcare quality for nursing management of IBD into 4 categories: A (highest
      quality) through D (lowest quality). CONCLUSION: the use of the NCQ-IBD tool to
      evaluate nursing management quality of IBD identifies areas in need of
      improvement and thus contribute to an enhancement of care quality and reduction
      in clinical practice variations.

PMID- 23971658
TI  - The attitudes of primary care providers towards screening for colorectal cancer.
AB  - BACKGROUND AND OBJECTIVE: the scientific community supports the appropriateness
      of colorectal cancer screening, and there is consensus on the need to raise
      awareness about the significance of prevention among both health care
      professionals and the population. The goal was to record the attitude of primary
      care providers towards colorectal cancer screening, as well as the main barriers
      to both patient and provider participation. METHODS: a cross-sectional,
      observational study was performed of 511 professionals in Albacete Health
      District. Variables included views on screening effectiveness and cost
      effectiveness, acceptance by providers and patients, barriers to participation,
      frequency of prevention recommendations, and education needs. RESULTS: most (76
      %) considered screening was effective; 85 % said acceptance of fecal occult blood
      testing was intermediate or high, and 68.2 % this is also the case for
      colonoscopy when needed; 71.9 % would recommend screening should a population
      based program be implemented (currently only 9.7 % recommends this).
      Correspondence analysis revealed that recommendation is more common when assigned
      populations are smaller. CONCLUSIONS: most providers consider screening is both
      effective and acceptable for patients. In today's situation, where screening is
      only performed in an opportunistic manner, the proportion of professionals who
      commonly recommend screening for the mid-risk population is low, especially when
      assigned populations are huge.

PMID- 23971659
TI  - Human intestinal dendritic cells as controllers of mucosal immunity.
AB  - Dendritic cells are the most potent, professional antigen-presenting cells in the
      body; following antigen presentation they control the type
      (proinflammatory/regulatory) of immune response that will take place, as well as
      its location. Given their high plasticity and maturation ability in response to
      local danger signals derived from innate immunity, dendritic cells are key actors
      in the connection between innate immunity and adaptive immunity responses. In the
      gut dendritic cells control immune tolerance mechanisms against food and/or
      commensal flora antigens, and are also capable of initiating an active immune
      response in the presence of invading pathogens. Dendritic cells are thus highly
      efficient in controlling the delicate balance between tolerance and immunity in
      an environment so rich in antigens as the gut, and any factor involving these
      cells may impact their function, ultimately leading to the development of bowel
      conditions such as celiac disease or inflammatory bowel disease. In this review
      we shall summarize our understanding of human intestinal dendritic cells, their
      ability to express and induce migration markers, the various environmental
      factors modulating their properties, their subsets in the gut, and the problems
      entailed by their study, including identification strategies, differences between
      humans and murine models, and phenotypical variations along the gastrointestinal
      tract.

PMID- 23971660
TI  - Retinal thrombosis secondary to the combination therapy of pegylated interferon
      and ribavirin for chronic hepatitis C virus infection. A rare complication.

PMID- 23971661
TI  - Primary intestinal Hodgkin's lymphoma associated with Crohn's disease.

PMID- 23971662
TI  - Krukenberg tumor after gastric bypass for morbid obesity. Bariatric surgery and
      gastric cancer.
AB  - Gastric bypass is one of the most frequently performed surgical procedures in
      bariatric surgery. A neoplasm within the gastric pouch is a somewhat infrequent
      complication but with important survival consequences. We present the case of a
      51-year-old woman who developed an adenocarcinoma in the bypassed stomach three
      years after bariatric surgery; the tumour was incidentally discovered after
      gynaecological surgery for uterine myomas. Various diagnostic modalities for the
      excluded stomach were analysed. 

PMID- 23971663
TI  - Crohn's-like disease in a patient with common variable immunodeficiency treated
      with azathioprine and adalimumab.
AB  - Common variable immunodeficiency (CVID) is the most frequent primary antibody
      deficiency. It is characterized by recurrent bacterial infections, and occurrence
      of autoimmune and neoplastic diseases is also frequent; there is also a high
      prevalence of gastrointestinal diseases. There are reports of inflammatory bowel
      disease in this entity, but incidence is low (2-4 %). We present the case of a
      patient with common variable immunodeficiency suffering a chronic diarrhea
      episode and who was diagnosed with ileocaecal Crohn s-like disease after
      performing intestinal transit, CT abdomen and colonoscopy with biopsy. It was
      first treated with prednisone but on showing cortisone dependency, treatment with
      azathioprine and adalimumab was started, with good results. 

PMID- 23971664
TI  - [Gastric MALT lymphoma].

PMID- 23971665
TI  - Hepatotoxicity and insomnia secondary to ranolazine.

PMID- 23971666
TI  - Dosage adjustment for hepatic dysfunction.

PMID- 23971667
TI  - Reply: "Dosage adjustment for hepatic dysfunction".

PMID- 23971668
TI  - Intestinal perforation in the immediate puerperium: A rare complication of
      bariatric surgery.

PMID- 23971669
TI  - Portal pneumatosis: Sign of alert or casual discovery?

PMID- 23971670
TI  - McKittrick-Wheelock syndrome - Prolapsed giant villous adenoma of the rectum.

PMID- 23971671
TI  - Third issue of 2013.

PMID- 23971672
TI  - Normal atrial conduction in medically treated patients with bulimia nervosa.
AB  - BACKGROUND: Bulimia nervosa (BN) patients are characterized by binge eating
      followed by compensatory behaviors. Ingestion of emetic substances,
      characteristic to some BN patients, has been reported to be associated with
      supraventricular arrhythmias. AIMS: To evaluate atrial electrocardiographic
      markers for supraventricular arrhythmias in patients with BN. METHOD: The cohort
      included 31 patients with BN and sex- and age-matched controls. Twelve-lead
      electrocardiography was conducted on all participants under strict standards. P
      wave length and P wave dispersion in each patient were computed from a randomly
      selected beat and an averaged beat constructed from 7-12 beats, included in a 10
      s ECG. RESULTS: No statistically significant differences were found between the
      groups for minimal, maximal, and average P wave duration and P wave dispersion,
      calculated either from a random beat or averaged beats. CONCLUSION: BN patients
      who are medically monitored and treated, have normal P wave parameters and P wave
      dispersion, and therefore do not appear to have an increased risk for developing
      supraventricular arrhythmias. Future research should focus on evaluating the
      effect of acute ingestion of emetic drugs on resting ECG of BN patients, as well
      as using signal averaging techniques and prolonged ECG-Holter monitoring.

PMID- 23971673
TI  - Epigenetic regulation of polyomavirus JC.
AB  - BACKGROUND: Polyomavirus JC (JCV) causes the CNS demyelinating disease
      progressive multifocal leukoencephalopathy (PML), which occurs almost exclusively
      in people with immune deficiencies, such as HIV-1/AIDS patients. JCV infection is
      very common and usually occurs early in life. After primary infection, virus is
      controlled by the immune system but, rarely when immune function is impaired, it
      can re-emerge and multiply in the astrocytes and oligodendrocytes in the brain
      and cause PML. Thus a central question in PML pathogenesis is the nature of the
      molecular mechanisms maintaining JCV in a latent state and then allowing
      reactivation. METHODS: Since transcription can be regulated by epigenetic
      mechanisms including DNA methylation and histone acetylation, we investigated
      their role in JCV regulation by employing inhibitors of epigenetic events.
      RESULTS: The histone deacetylase inhibitors trichostatin A (TSA) and sodium
      butyrate powerfully stimulated JCV early and late transcription while the DNA
      methylation inhibitor 5-azacytidine had no effect. Analysis of JCV mutants showed
      that this effect was mediated by the KB element of the JCV control region, which
      binds transcription factors NF-kappaB p65, NFAT4 and C/EBPbeta and mediates
      stimulation by TNF-alpha. Stimulation of transcription by p65 was additive with
      TSA as was cotransfection with transcriptional coactivators/acetyltransferase
      p300 whereas depletion of endogenous p65 by RNA interference inhibited the effect
      of TSA. EMSA with a KB oligonucleotide showed p65 expression, TNF-alpha
      stimulation or TSA treatment each caused a gel shift that was further shifted by
      antibody to p65. CONCLUSIONS: We conclude that JCV is regulated epigenetically by
      protein acetylation events and that these involve the NF-kappaB p65 binding site
      in the JCV control region.

PMID- 23971674
TI  - The effect of regular physical activity on bone mineral density in post
      menopausal women aged 75 and over: a retrospective analysis from the Canadian
      multicentre osteoporosis study.
AB  - BACKGROUND: Physical activity is known to benefit many physiological processes,
      including bone turnover. There are; however, currently no clinical guidelines
      regarding the most appropriate type, intensity and duration of activity to
      prevent bone loss. METHODS: To help address this gap in the literature, we
      performed a retrospective analysis of data from the Canadian Multicentre
      Osteoporosis Study (CaMos), a prospective cohort of 9423 adult patients, to
      determine the relationship between the amount of regular daily physical activity
      performed and bone mineral density. A total of 1169 female participants aged 75
      and over provided information regarding their daily activity levels, including
      the amount of time spent each week performing physical activity at varying levels
      of intensity. Multiple and linear regression analyses were used to determine the
      effect of increasing amounts of this regular physical activity on bone mineral
      density. RESULTS: The results indicate that a step increase in the amount of
      physical activity performed each day resulted in a positive effect on bone
      mineral density at the hip, Ward's triangle, trochanter and femoral neck (B =
      0.006 to 0.008, p < 0.05). Possible confounding factors such as the use of anti
      resorptive therapy, body mass index and age were included in the analysis and
      suggested that age had a negative effect on bone density while body mass index
      had a positive effect. Anti-resorptive therapy provided a protective effect
      against loss of bone density. CONCLUSIONS: The data indicate that a step increase
      in the amount of daily activity, using simple, daily performed tasks, can help
      prevent decreases in post-menopausal bone mineral density.

PMID- 23971675
TI  - Reflections on tuberculosis diagnosis and treatment outcomes in Ghana.
AB  - BACKGROUND: Available evidence in Ghana shows the implementation of tuberculosis
      (TB) control activities efforts since the beginning of the 1900s. In spite of
      that, TB continues to be one of the common diseases in the country. In 1994,
      local and international policy windows opened for renewed strategies for the
      control of TB. This paper explores some of the approaches which have been in
      place since 1994 and their implications for treatment outcomes. METHODS: The
      study combines quantitative and qualitative data. The quantitative data consist
      of treatment outcome from 1997-2010 and the qualitative data are derived from in
      depth interviews with some staff of the TB control programme. Poisson regression
      and inductive coding were applied to the quantitative and qualitative data
      respectively. RESULTS: Reported cure rates increased from 43.6% to 87.7% between
      1997 and 2010. The data from the in-depth interviews (IDIs) suggested that
      improvements in diagnosis, community TB care, stigma reduction among community
      and health workers towards TB patients, the public-private partnership, and the
      enablers' package contributed to the improved better treatment outcomes,
      particularly from 2008. CONCLUSIONS: Lessons learnt include the achievement of
      objectives with varying strategies and stakeholder interventions. Further studies
      would be needed to quantify the contributions of the various interventions to
      help determine those that are cost effective as well as efficient and effective
      for TB control.

PMID- 23971676
TI  - Conjugated polymer/nanoparticles nanocomposites for high efficient and real-time
      volatile organic compounds sensors.
AB  - The present work demonstrates a high efficient and low cost volatile organic
      compounds (VOCs) sensor. Nowadays, VOCs, which are typically toxic, explosive,
      flammable, and an environmental hazard, are extensively used in R&D laboratories
      and industrial productions. Real-time and accurately monitoring the presence of
      harmful VOC during the usage, storage, or transport of VOCs is extremely
      important which protects humans and the environment from exposure in case of an
      accident and leakage of VOCs. The present work utilizes conducting
      polymer/nanoparticles blends to sense various VOCs by detecting the variation of
      optical properties. The novel sensor features high sensitivity, high accuracy,
      quick response, and very low cost. Furthermore, it is easy to fabricate into a
      sensing chip and can be equipped anywhere such as a laboratory or a factory where
      the VOCs are either used or produced and on each joint between transporting pipes
      or each switch of VOC storage tanks. Real-time sensing is achievable on the basis
      of the instant response to VOC concentrations of explosive limits. Therefore, an
      alarm can be delivered within a few minutes for in time remedies. This research
      starts from investigating fundamental properties, processing adjustments, and a
      performance test and finally extends to real device fabrication that practically
      performs the sensing capability. The demonstrated results significantly advance
      the current sensor technology and are promising in commercial validity in the
      near future for human and environmental safety concerns against hazardous VOCs. 

PMID- 23971678
TI  - Improved detection of transgene and nonviral vectors in blood.
AB  - Vector biodistribution and clearance studies are essential in the development of
      gene transfer medicine. To provide reliable and accurate data, protocols for
      vector analysis must be optimized and validated. We addressed several parameters
      affecting the detection of gene therapy vectors in blood. Using an in vitro
      system based on plasmid DNA incorporating, as a transgene, complementary DNA for
      human erythropoietin gene, we developed and validated a suite of real-time PCR
      assays for the transgene splicing sites. The most sensitive assays detected the
      transgene present at 0.011% of the copy number of the endogenous erythropoietin
      gene in human genomic DNA at 100% specificity. Plasmid linearization incorporated
      with PCR resulted in an increase in assay sensitivity up to 4.5-fold without
      compromising analysis workflow. This allowed detection of five copies of
      transgene in a background of 0.4 MUg of genomic DNA (or 0.0035% detectable
      transgene copies relevant to copies of the endogenous gene). Finally, desktop
      assessment of 18 DNA extraction protocols was undertaken and 5 kits were
      evaluated experimentally for extraction of nonviral vectors from blood. Three
      kits reliably detected 80 copies of the transgene in a milliliter of blood.
      Adoption of the described protocols will enable more reliable vector analysis in
      gene therapy and will assist in accurate interlaboratory comparison. The
      methodology will also facilitate detection of gene doping in sport, a potential
      new form of misuse of gene transfer technology.

PMID- 23971677
TI  - Beneficial effects of coating alginate microcapsules with macromolecular heparin
      conjugates-in vitro and in vivo study.
AB  - Pericapsular fibrotic overgrowth (PFO) is associated with poor survival of
      encapsulated pancreatic islets. Modification of the microcapsule membrane aimed
      at preventing PFO should improve graft survival. This study investigated the
      effect of macromolecular Corline Heparin Conjugate (CHC) binding on intrinsic
      properties of alginate microcapsules and assessed the anti-fibrotic potential of
      this strategy both in vitro and in vivo. CHC was bound to alginate microcapsules
      using a layer-by-layer approach incorporating avidin. CHC binding to alginate
      microcapsule was visualized by confocal microscopy. Effects of CHC binding on
      microcapsule size, strength, and permeability were assessed, and the anti
      clotting activity of bound CHC was determined by coagulation assay. Effect of CHC
      binding on the viability of encapsulated human islets was assessed in vitro, and
      their ability to function was assessed both in vitro and in vivo in diabetic
      immunodeficient mice. The potential of bound CHC to reduce PFO was assessed in
      vivo in different rat transplantation models. Confocal microscopy demonstrated a
      uniform coating of CHC onto the surface of microcapsules. CHC binding affected
      neither size nor permeability but significantly increased the tensile strength of
      alginate microcapsules by ~1.3-fold. The bound CHC molecules were stable and
      retained their anti-clotting activity for 3 weeks in culture. CHC binding
      affected neither viability nor function of the encapsulated human islets in
      vitro. In vivo CHC binding did not compromise islet function, and diabetes was
      reversed in all recipients with mice exhibiting lower blood glucose levels
      similar to controls in oral glucose tolerance tests. CHC binding was beneficial
      and significantly reduced PFO in both syngeneic and allogeneic rat
      transplantation models by ~65% and ~43%, respectively. In conclusion, our results
      show a new method to successfully coat CHC on alginate microcapsules and
      demonstrate its beneficial effect in increasing capsule strength and reduce PFO.
      This strategy has the potential to improve graft survival of encapsulated human
      islets.

PMID- 23971679
TI  - Upper limb post-stroke sensory impairments: the survivor's experience.
AB  - PURPOSE: This study described stroke survivors' experiences of upper limb post
      stroke sensory impairment (ULPSSI) and its rehabilitation. METHODS: A qualitative
      descriptive study of 15 stroke survivors with ULPSSI using semi-structured
      interviews. A focus group of eight survivors reviewed thematic outcomes. Analysis
      was completed by three authors. RESULTS: Three themes emerged: (1) What happened
      to my hand?: A description of the significant impact of sensory impairments on
      survivors roles and participation; (2) I was only just getting started: Survivors
      felt sensory impairments and the upper limb were ignored in rehabilitation and
      described being left on their own to devise their own rehabilitation; and (3) If
      I work hard then maybe someday: Survivors felt sensory impairments recovered
      slowly and was aided by working towards recovery and maintaining hope.
      CONCLUSIONS: Sensory impairments are significant for survivors and are deserving
      of greater clinical and research attention. In particular, assessments and
      interventions need further development and testing. This study's findings
      revealed the need to ascertain individual survivors' preference for involvement
      in decision making related to their rehabilitation planning. It also found
      survivors view recovery as extending well beyond current rehabilitation
      frameworks, necessitating further description of recovery and re-evaluation of
      service delivery to address survivors' needs. IMPLICATIONS FOR REHABILITATION:
      Sensory impairments significantly impact stroke survivors' roles and
      participation. Remediation of sensory impairments is important to survivors, but
      seems to be ignored in the rehabilitation process. Individual survivors'
      preference for involvement in decision making related to their rehabilitation
      planning should be ascertained. Stroke survivors feel left on their own to
      address their upper limb impairments long after rehabilitation services have
      ended. The development of services beyond the normal rehabilitation timeframes is
      warranted.

PMID- 23971680
TI  - Invasive Mycobacterium marinum infection of the hand.
AB  - Mycobacterium marinum infection of the hand is rare. We report the case of a 39
      year-old man with M marinum infection that resulted in a chronic soft tissue
      infection, extensor tendon synovitis, and arthritis of the metacarpophalangeal
      (MCP) joints. The cause was probably tropical freshwater fishes.

PMID- 23971681
TI  - Angioleiomyoma of the pulp.
AB  - Vascular leiomyomas or angioleiomyomas are benign solitary smooth muscular
      tumours that rarely occur in the distal finger. I report a 64-year-old man with
      uncommon clinical appearance in the pulp of the middle finger.

PMID- 23971682
TI  - Treatment of breakthrough cancer pain: to titrate or to proportionate?
AB  - Breakthrough cancer pain can be treated effectively by rapid-onset opioids, such
      as sublingual fentanyl. However, it remained unclear how the optimal dose of
      sublingual fentanyl should be determined. Dosing proportional to basic opioid
      regimen is now proposed as an alternative to dose titration.

PMID- 23971684
TI  - Relations of human breastmilk choline content with maternal hormonal status.

PMID- 23971683
TI  - Increased breastfeeding rates in black women after a treatment intervention.
AB  - There has been a considerable increase in rates of breastfeeding in the United
      States. Despite these trends, black women continue to fall below medical
      recommendations. Impoverished and poorly educated women also have a comparatively
      lower rate of breastfeeding. Provider encouragement and supportive interventions
      increase breastfeeding initiation among women of all backgrounds. The data
      presented come from a three-site randomized controlled bilingual depression
      treatment trial from 2005 to 2011 that examined the comparative effectiveness of
      interpersonal psychotherapy and a parenting education program. Breastfeeding
      education and support were provided for the majority of participants in each
      intervention. Breastfeeding status was queried at postpartum week 4. We found
      higher rates of breastfeeding in black women compared with those reported in
      national surveys. The black breastfeeding rate did not significantly differ from
      that of white or Hispanic women. American-born black women were just as likely to
      breastfeed as American-born white women, both at significantly greater rates than
      American-born Hispanic women. We also found no differences in breastfeeding rate
      in poorly educated and impoverished women. These data must be seen against the
      backdrop of a significant intervention to treat depression. Because breastfeeding
      interventions have been shown to increase breastfeeding rates, the support
      provided in our study likely increased rates in groups that lag behind.

PMID- 23971686
TI  - Chronic catatonia treated with electroconvulsive therapy: a case report.
AB  - INTRODUCTION: In the International Statistical Classification of Diseases and
      Related Health Problems 10 and Diagnostic and Statistical Manual of Mental
      Disorders IV classification systems, catatonia is classified as a subtype of
      schizophrenia. However, catatonia is more frequently associated with mood
      disorders than schizophrenia. It is also associated with organic conditions.
      Catatonia responds to treatment with benzodiazepines and electroconvulsive
      therapy rather than antipsychotics. These features support the categorization of
      catatonia as an independent syndrome. There is a lack of consensus regarding the
      definition of chronic catatonia. There are two previous case reports of effective
      treatment of chronic catatonia with electroconvulsive therapy. CASE PRESENTATION:
      A 29-year-old South Asian woman was admitted to hospital because of poor food
      intake. Her condition had progressively worsened over the past seven months. She
      had features of catatonia. On admission, her Bush-Francis Catatonia Rating Scale
      score was 24. Her symptoms resolved after the administration of 17
      electroconvulsive therapies but recurred later. She was given a further four
      electroconvulsive therapies. She remains well on aripiprazole at a dose of 60mg a
      day. CONCLUSIONS: Bilateral electroconvulsive therapy is effective in the
      treatment of chronic catatonia and should be considered as a treatment option. A
      relapse of symptoms can occur after the discontinuation of treatment.

PMID- 23971685
TI  - Buying human milk via the internet: just a click away.
AB  - BACKGROUND: For past centuries, infants have been fed the milk of mothers who are
      not their own by latching to another woman's breast. Today, the majority of
      lactating women use electric pumps to extract milk from their breasts; thus, an
      infant now may be fed another woman's milk via a bottle or cup. The Internet is
      an emerging avenue to acquire pumped human milk. The purpose of our study was to
      participate in and describe the process of buying milk via the Internet. Our goal
      is to help those involved with the clinical care, research, and public health
      policy of mothers and infants better understand that families may be buying milk
      in this way. SUBJECTS AND METHODS: We anonymously bought 102 human milk samples
      via the Internet. We characterized the outside box, packing materials, milk
      container, temperature and condition of the milk, and cost. RESULTS: We bought
      2,131 ounces of milk at a total cost of $8,306. Eighty-nine percent of the milk
      arrived above the recommended frozen temperature of -20 degrees C; 45% of it was
      even above the recommended refrigerator temperature (4 degrees C). The mean
      surface temperature of the milk samples in each shipment was correlated with the
      cost of shipping, time in transit, and condition of the milk containers.
      CONCLUSIONS: The prevalence and potential risks of this practice currently are
      unknown. Research related to milk quality and infant outcomes related to milk
      buying via the Internet is urgently needed.

PMID- 23971687
TI  - Polymorphonuclear counts in ascitic fluid and microorganisms producing
      spontaneous bacterial peritonitis: an under-recognized relationship.
AB  - BACKGROUND AND AIMS. In cirrhotic patients with spontaneous bacterial peritonitis
      (SBP) higher polymorphonuclear (PMN) count in ascitic fluid have been reported in
      infections caused by Gram-negative bacilli (GNB) as opposed to Gram-positive
      cocci (GPC). However, the influence of other associated factors on the PMN count,
      such as the specific microorganism causing the episode of SBP, has not been well
      established. METHODS. Retrospective observational study of 194 episodes of
      positive ascitic and/or blood culture SBP in 159 patients with liver cirrhosis
      (2001-2009). Parameters associated with PMN count in ascitic fluid at diagnosis
      were evaluated. RESULTS. The multivariate analysis (model 1) showed that a
      virulent etiology of the infection [coefficient 3.941 (95% confidence interval
      (95 CI): 0.421-7.461)] and the model for end-stage liver disease (MELD) score
      [coefficient 0.196 (95 CI: 0.007-0.384)] were positively associated with the PMN
      count in ascites, while a nosocomial acquisition was inversely associated
      [coefficient -3.546 (95 CI: -6.855 - -0.238)]. A nonsignificant trend toward
      higher PMN count was found in GNB versus GPC, but there were differences between
      groups of microorganisms: pyogenic streptococci [median (p25-p75): 3211 (1615
      8004)], Enterobacteriaceae [2958 (917-7690)], Vibrionaceae [9215 (375-17280)],
      nonfermenting GNB [1384 (565-3865)], viridans group streptococci [1044 (503
      2354)] and enterococci [1050 (476-4655)](p = 0.005). No clear cut-offs of ascitic
      PMN count predicting a particular etiology could be calculated out of these data.
      CONCLUSIONS. In cirrhotic patients with SBP, the causing microorganism, the place
      of acquisition of the infection and the host liver condition were the main
      factors determining PMN count in ascitic fluid. Third-generation cephalosporin
      resistance was associated with low PMN count probably because this group included
      bacteria with inherent low virulence.

PMID- 23971688
TI  - Renin-angiotensin system in neuronal disease.

PMID- 23971689
TI  - Do RAS inhibitors protect the brain from cerebral ischemic injury?
AB  - In addition to centrally regulating electrolyte homeostasis and blood pressure,
      angiotensin IIhas various general effects on the central nervous system. The
      existence of renin-angiotensin system components in the brain has been well
      established. Angiotensin II and other renin-angiotensin system components are
      synthesized and distributed throughout the brain. Post-ischemic oral
      administration of a non-hypotensive dose (1/10th of the clinical dose) of
      angiotensin receptor blocker (ARB) has protective effects on reducing cerebral
      ischemic injury and improving neurological outcomes. Brain tissue angiotensin II
      levels transiently increase after reperfusion through the local generation of
      angiotensin IIand not via the transudation of plasma angiotensin II. Systemic
      administration of ARBs decreases brain tissue angiotensin II in both the intact
      and ischemic brain tissue via downregulation of angiotensinogen and angiotensin
      converting enzyme mRNA expression, although plasma ARB barely crosses the blood
      brain barrier during systemic ARB treatment. Only hypotensive dose of ARB
      treatment opens leptomeningeal anastomoses. Therefore, systemic ARB treatment
      shows neuroprotective effects not through increasing collateral perfusion but
      decreasing brain tissue angiotensin II in a nonhypotensive dose. 

PMID- 23971690
TI  - RAS inhibition attenuates cognitive impairment by reducing blood- brain barrier
      permeability in hypertensive subjects.
AB  - Recent studies have suggested that blood-brain barrier (BBB) abnormalities are
      present from an early stage in patients exhibiting mild symptoms of cognitive
      impairment during the development of hypertension. There is also growing body of
      evidence suggesting the potential role of the renin-angiotensin system (RAS) in
      the pathogenesis of small-vessel disease and cognitive impairment. However, the
      specific contribution of the RAS to BBB disruption and cognitive impairment
      remains unclear. We found a significant leakage from brain microvessels in the
      hippocampus and impaired cognitive functions in angiotensin II (AngII)-infused
      hypertensive mice, which were associated with increased brain AngII levels. These
      changes were not observed in AngII-infused AT1a receptor (-/-) mice. We also
      observed that Dahl salt-sensitive hypertensive rats exhibited hypertension,
      leakage from brain microvessels in the hippocampus, and impaired cognitive
      function. In these animals, treatment with an AngII receptor blocker, olmesartan,
      did not alter blood pressure, but markedly ameliorated leakage from brain
      microvessels and restored the cognitive decline. These data support the
      hypothesis that RAS inhibition attenuates cognitive impairment by reducing BBB
      injury, which is independent of blood pressure changes. 

PMID- 23971691
TI  - Therapeutic approach for neuronal disease by regulating renin-angiotensin system.
AB  - The renin-angiotensin system (RAS) has been postulated to regulate not only
      systemic hemodynamic and hydromineral homeostasis but also individualorgan
      function in the normal condition. On the other hand, its systemic and
      localactivationleads to hypertension and diabetes mellitus,resulting intarget end
      organ damage.RAS in the brain is also well known to be involved in the
      pathogenesis and progression of neuronal disease, as well as regulating blood
      pressure, sympathetic activity, vasopressin secretion, thirst and sodium
      appetite.There is increasing evidence that RAS may contribute to
      neuroinflammation associated with many neuronal diseases in several animal
      models. Moreover, recent clinical evidence indicates that RAS blockade, including
      that byangiotensin converting enzyme inhibitors and angiotensin II receptor
      blockers, has beneficial effects in treating stroke, cognitive dysfunction,
      Alzheimer disease and other neuronal diseases, suggesting the potential of RAS as
      a new therapeutic target in neuronal diseases. This article reviews the recent
      findings ofbrain RAS involvement and thetherapeutic potential of regulating RAS
      in neuronal disease. 

PMID- 23971692
TI  - Renoprotective effects of the L-/T-type calcium channel blocker benidipine in
      patients with hypertension.
AB  - The renoprotective effects of benidipine, a calcium channel blocker (CCB)
      developed in Japan, are reviewed herein. Benidipine has a sustained
      antihypertensive effect independent of its blood concentration since it binds to
      dihydropyridine (DHP) receptors via a "membrane approach" (approach to the cell
      membrane followed by long retention at the DHP binding site). Benidipine dilates
      glomerular afferent and efferent arterioles equally through inhibition of Ttype
      Ca channels. Thus, it may cause a decrease of intraglomerular pressure and is
      superior to CCBs (capable of inhibiting only L-type Ca channels) in terms of
      suppression of proteinuria. Additionally, benidipine suppresses worsening of
      renal function more powerfully than CCBs (suppressing only L-type Ca channels),
      allowing better prognosis as to renal function. The inhibitory effect of
      benidipine on T-type calcium channels results in the suppression of aldosterone
      formation in the adrenal glands and of oxidative stress induced by aldosterone.
      Thus, the aldosterone-inhibitory and antioxidant activities of benidipine
      mediated by inhibition of T-type calcium channels would result in renoprotection
      and suppression of disease progression in hypertensive patients with chronic
      kidney disease (CKD). If such patients have proteinuria, renin-angiotensin system
      (RAS) inhibitors are used as first-line drugs, but benidipine, as an L-/T-type
      CCB, is recommended when they require some concomitant drugs. Moreover, the
      superiority of RAS inhibitors has not been demonstrated in hypertensive patients
      with CKD and without proteinuria. Thus, in such patients, benidipine should be
      considered as a first-line antihypertensive drug. 

PMID- 23971693
TI  - Rationale and design of an observational study to determine the effects of
      cholecalciferol on hypertension, proteinuria and urinary MCP-1 in ADPKD.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic
      cause of kidney failure in the world. Currently there are no treatments to
      prevent kidney due to ADPKD. Vitamin D is traditionally known for its role in
      maintaining calcium balance and normal bone health, but it is being increasingly
      being recognised for a number of other important physiological functions,
      including reducing blood pressure and proteinuria as well as kidney inflammation
      andfibrosis. Vitamin D deficiency is associated with proteinuria, increased
      mortality and may mediate the progression to kidney failure. Recent data from an
      Australian cohort study (AusDiab) reveals that vitamin D deficiency and
      insufficiency are common conditions, affecting 26.6% and 42.1% of the Australian
      community respectively. Preclinical studies from our laboratory have identified
      that vitamin D deficiency exacerbates proteinuria and hypertension in
      experimental PKD, and that this is reversed by treatment with vitamin D receptor
      agonist. In this manuscript, we report the rational and design of an open-label
      observational study of humans with ADPKD (eGFR>30 ml/min/1.73m2). All subjects
      will undergo screening for vitamin D levels at the beginning of study, and those
      that are found to be either deficient (<50 nmol/L) or insufficient (<75 nmol/L)
      will be repleted with oral cholecalciferol for 6 months. We predict that
      cholecalciferol will attenuate hypertension, proteinuria and reduce the urinary
      excretion of a biomarker, monocyte chemoattractant protein-1 (MCP-1, a surrogate
      inflammatory marker of progression in ADPKD). This study will provide evidence as
      to whether a simple intervention such as vitamin D repletion, in either deficient
      or insufficient states, is a treatment to prevent kidney failure in ADPKD. 

PMID- 23971694
TI  - Interactions between the sympathetic nervous system and angiotensin system in
      renovascular hypertension.
AB  - Renal artery stenosis especially that due to atherosclerotic peripheral vascular
      disease is increasing in the population. The role of the renin angiotensin
      aldosterone system in the pathogenesis of renovascular hypertension is widely
      accepted. There is increasing recognition of the role of the sympathetic nervous
      system, from both afferent and efferent signaling pathways, as a contributor to
      development of hypertension. In this review we briefly summarize the experimental
      evidence for the respective roles of the renin angiotensin aldosterone system and
      the sympathetic nervous system as well as their interaction in renovascular
      hypertension. 

PMID- 23971695
TI  - The promises and challenges of the use of genomics in the prescription of
      exercise for hypertension: the 2013 update.
AB  - Hypertension is a major global public health problem, resulting in over 7.6
      million deaths per year (13.5% of the total), more than any other cardiovascular
      disease risk factor. Exercise decreases blood pressure (BP) 5-7 mmHg among those
      with hypertension. Thus, the American College of Sports Medicine recommends the
      exercise prescription (ExRx) of 30 min or more of moderate intensity, aerobic
      activity on most days of the week to lower BP. Yet, there is considerable
      individual variability in the BP response to exercise due to genetic and
      environmental factors that are poorly understood. We and others have shown there
      is a genetic component to the BP response to exercise accounting for a
      significant proportion of this variability. However, identification of specific
      genetic variants accounting for this variability is a significant challenge. This
      review describes new work on candidate gene and BP association studies. It also
      describes other important emerging work in genome wide association studies, next
      generation sequencing, epigenetics, and gene expression regulation, and how this
      work may have future relevance to ExRx for hypertension. The ultimate goal of our
      research is to use genetic information to personalize ExRx to optimize the
      effectiveness of exercise as a therapeutic modality for the prevention,
      treatment, and control of hypertension. Because of the complexities surrounding
      work in exercise genomics, the future use of genomics in ExRx for hypertension
      still remains a vision of the future rather than a reality of the present. 

PMID- 23971696
TI  - Roles of renal proximal tubule transport in the pathogenesis of hypertension.
AB  - Hypertension is a key factor of cardiovascular disease. Many organs and systems
      including heart, blood vessel, kidney, sympathetic nerve, and endocrine systems
      are involved in the regulation of blood pressure. In particular, the kidney plays
      an essential role in the regulation of blood pressure, but is also quite
      vulnerable to hypertensive tissue damage. For example, most chronic kidney
      disease (CKD) patients have hypertension and are revealed to have higher
      mortality than normal population. Furthermore, hypertensive renal sclerosis is
      emerging as the third main cause of dialysis patients. This mini review is to
      summarize the effects of angiotensin II and dopamine on renal proximal tubule
      transport, which may have important roles in the regulation of blood pressure. 

PMID- 23971697
TI  - Diagnosis and treatment of unilateral forms of primary aldosteronism.
AB  - Primary aldosteronism (PA) is now recognized as the most frequent form of
      secondary arterial hypertension. The importance of a correct and prompt diagnosis
      of PA is determined by its relevant prevalence, its increased cardiovascular risk
      compared to essential hypertension and by the possibility of reversing this
      increased risk with a targeted therapy. Surgical treatment of unilateral forms of
      PA (mainly aldosterone-producing adenomas) is at present recommended in well
      selected patients because of its cost-effectiveness. Therefore, subtype
      differentiation of PA forms is of fundamental importance, and available
      guidelines recommend contrast-enhanced CT-scanning and adrenal venous sampling
      (AVS) as the main diagnostic tests for this purpose. In this review, we discuss
      the value of adrenal non-invasive imaging and AVS, the recent advances in
      complementary tests and, finally, the available data on the outcome of surgical
      treatment for PA. 

PMID- 23971699
TI  - Development and validation of duplex, triplex, and pentaplex real-time PCR
      screening assays for the detection of genetically modified organisms in food and
      feed.
AB  - Worldwide, qualitative methods based on PCR are most commonly used as screening
      tools for genetically modified material in food and feed. However, the increasing
      number and diversity of genetically modified organisms (GMO) require effective
      methods for simultaneously detecting several genetic elements marking the
      presence of transgenic events. Herein we describe the development and validation
      of a pentaplex, as well as complementary triplex and duplex real-time PCR assays,
      for the detection of the most common screening elements found in commercialized
      GMOs: P-35S, T-nos, ctp2-cp4-epsps, bar, and pat. The use of these screening
      assays allows the coverage of many GMO events globally approved for
      commercialization. Each multiplex real-time PCR assay shows high specificity and
      sensitivity with an absolute limit of detection below 20 copies for the targeted
      sequences. We demonstrate by intra- and interlaboratory tests that the assays are
      robust as well as cost- and time-effective for GMO screening if applied in
      routine GMO analysis. 

PMID- 23971698
TI  - Improved quenched fluorescent probe for imaging of cysteine cathepsin activity.
AB  - The cysteine cathepsins are a family of proteases that play important roles in
      both normal cellular physiology and many human diseases. In cancer, the activity
      of many of the cysteine cathepsins is upregulated and can be exploited for tumor
      imaging. Here we present the design and synthesis of a new class of quenched
      fluorescent activity-based probes (qABPs) containing a phenoxymethyl ketone (PMK)
      electrophile. These reagents show enhanced in vivo properties and broad
      reactivity resulting in dramatically improved labeling and tumor imaging
      properties compared to those of previously reported ABPs. 

PMID- 23971700
TI  - The increasing use of genetically-altered animals threatens the credibility of
      Directive 2010/63/EU.

PMID- 23971701
TI  - Comparative studies of apoptosis in Xenopus laevis and mouse thymoma cell lines.
AB  - With the use of in vitro methods and cell lines, functional aspects of apoptosis
      in the Xenopus laevis B3/B7 and mouse EL4 thymoma cell lines are revealed.
      Moreover, by using information gleaned from digital imaging and
      immunocytochemistry, changes in locations of key proteins implicated in apoptotic
      anti-cancer responses, e.g. p53 and Mdm2, are shown. Suggestions are offered as
      to what these results might mean with respect to the evolutionary conservation of
      the function and structure of these two molecules and to cancer resistance in
      amphibians. Finally, studies are described on resveratrol as an anti-cancer
      therapeutic reagent in the two thymoma cell lines and in normal X. laevis
      thymocytes. 

PMID- 23971702
TI  - Fish as research tools: alternatives to in vivo experiments.
AB  - The use of fish in scientific research is increasing worldwide, due to both the
      rapid expansion of the fish farming industry and growing awareness of questions
      concerning the humane use of mammalian models in basic research and chemical
      testing. As fish are lower on the evolutionary scale than mammals, they are
      considered to be less sentient. Fish models are providing researchers, and those
      concerned with animal welfare, with opportunities for adhering to the Three Rs
      principles of refinement, reduction and replacement. However, it should be kept
      in mind that fish should also be covered by the principles of the Three Rs.
      Indeed, various studies have shown that fish are capable of nociception, and of
      experiencing pain in a manner analogous to that in mammals. Thus, emphasis needs
      to be placed on the development of alternatives that replace, as much as
      possible, the use of all living vertebrate animals, including fish. This review
      gives the first comprehensive and critical overview of the existing alternatives
      for live fish experimental studies. The alternative methods described range from
      cell and tissue cultures, organ and perfusion models, and embryonic models, to in
      silico computer and mathematical models. This article aspires to guide scientists
      in the adoption of the correct alternative methods in their research, and,
      whenever possible, to reduce the use of live fish. 

PMID- 23971703
TI  - Resistance to cancer in amphibians: a role for apoptosis?
AB  - The rarity of spontaneous cancer in amphibians, and the difficulty of inducing
      cancer in these lower vertebrates, suggest that they possess an effective system
      for resistance to the development of cancer. The first part of this narrative
      presents evidence for cancer resistance in amphibians, and then a variety of
      studies designed to help understand the physiological basis for this resistance
      are reviewed. Here, our emphasis is on evidence with regard to the role that
      apoptosis might play. 

PMID- 23971704
TI  - Is phenylbutazone a genotoxic carcinogen? A weight-of-evidence assessment.
AB  - Published in silico, in vitro, in vivo laboratory animal and human data, together
      with information on biotransformation and data from structure-activity analyses
      with two decision-tree systems (ACToR and Toxtree), have been used in a weight-of
      evidence (WoE) assessment to determine whether phenylbutazone (PBZ) is a
      genotoxic or a non-genotoxic carcinogen. This was undertaken to facilitate the
      risk assessment of human exposure to this veterinary drug via the consumption of
      horsemeat from treated animals. Despite problems with data interpretation at all
      tiers of the database, it was concluded that PBZ behaves like a genotoxic
      carcinogen with a threshold dose. This conclusion is based mainly on the results
      of a definitive rodent bioassay, and on the following observations: a) that PBZ
      has weak in vitro activity only at high concentrations in some genotoxicity
      assays, accompanied by high levels of cytotoxicity; b) that it (and a major
      metabolite) is able to cause sister chromatid exchanges in vivo in rodents; and
      c) that it can induce cytogenetic effects in vivo in humans. It also takes into
      account the known and predicted activities of the parent drug, some of its
      metabolites and two structural analogues, and, importantly, several of the drug's
      other biochemical effects that are unrelated to toxicity. However, this
      conclusion is not fully supported by all the evidence, and much of the
      information is based on old papers. Therefore, more studies are required to
      establish whether the concentration thresholds seen in vitro would translate to
      dose thresholds for carcinogenicity, such that a safe dose-level could be defined
      for the purposes of assessing risk. It was disappointing that a WoE approach to
      evaluating all of the available hazard data, as is increasingly being advocated
      to improve the hazard identification paradigm, was unable to provide definitive
      answers in this case, particularly in view of the large numbers of animals that
      had been used to provide much of the information. 

PMID- 23971705
TI  - Refinement: lessons from the 2012 Olympics.

PMID- 23971706
TI  - Refinement.

PMID- 23971707
TI  - Balancing reduction and refinement.

PMID- 23971708
TI  - 5. Refinement.

PMID- 23971709
TI  - Effects of initiating palliative care consultation in the emergency department on
      inpatient length of stay.
AB  - BACKGROUND/OBJECTIVE: Increased attention has been directed at the intersection
      of emergency and palliative medicine, since decisions made in the emergency
      department (ED) often determine the trajectory of subsequent medical treatments.
      Specifically, we examined whether inpatient admissions after palliative care (PC)
      consultation initiated in the ED were associated with decreased length of stay
      (LOS), compared with those in which consultations were initiated after hospital
      admission. METHODS: Education and training on PC and the consultation service
      were provided to ED physicians and nurses. The PC service evaluated patients in
      the ED during weekdays and provided telephone consultation nights and weekends
      with postadmission follow-up. We compared the outcomes of these patients with
      those whose PC needs were identified and addressed through consultation
      postadmission. PC consultation data between January 2006 and December 2010 were
      retrospectively collected from the administrative records system and analyzed
      using propensity scores within multivariate regression. RESULTS: Included in the
      analysis were 1435 PC consultations, 50 of which were initiated in the ED across
      the 4-year study period. Propensity scores were calculated using patient-level
      characteristics, including All Patient Refined Diagnostic Related Group (APRDRG)
      risk of mortality (ROM) and severity of illness (SOI), age, gender, readmission
      status, facility, and insurance type. Regression results showed that consultation
      in the ED was associated with a significantly shorter LOS by 3.6 days (p<0.01).
      CONCLUSIONS: Early initiation of PC consultation in the ED was associated with a
      significantly shorter LOS for patients admitted to the hospital, indicating that
      the patient- and family-centered benefits of PC are complemented by reduced
      inpatient utilization.

PMID- 23971710
TI  - Low-dose buprenorphine patch for pain #268.

PMID- 23971711
TI  - Synergistic effects of sequential infection with highly pathogenic porcine
      reproductive and respiratory syndrome virus and porcine circovirus type 2.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is the
      causative agent of porcine reproductive and respiratory syndrome (PRRS) and
      porcine circovirus type 2 (PCV2) is associated with postweaning multisystemic
      wasting syndrome (PMWS) in pigs. Coinfection with highly pathogenic PRRSV (HP
      PRRSV) and PCV2 in the field has recently become extensive in some Asian
      countries. A synergistic pathogenicity between PRRSV and PCV2 infections has
      previously been reported. However, the consequences of the sequential infection
      of pigs with these two viruses are unknown. METHODS: Thirty 35-day-old piglets
      were randomly divided into six groups (n = 5 each): HP-PRRSV/PCV2 (group 1,
      inoculated with HP-PRRSV, then inoculated with PCV2 one week later), PCV2/HP
      PRRSV (group 2, inoculated with PCV2, then inoculated with HP-PRRSV one week
      later), HP-PRRSV+PCV2 (group 3, inoculated with HP-PRRSV and PCV2 concurrently),
      HP-PRRSV (group 4, inoculated with HP-PRRSV), PCV2 (group 5, inoculated with
      PCV2), and the control (group 6, uninfected). This experiment lasted 28 days.
      Clinical symptoms and rectal temperatures were recorded each day after
      inoculation, body weight was recorded weekly, and serum samples were obtained for
      viral nucleic acid quantification and antibody titration. Variations in CD3+,
      CD4+ CD8-, CD3+, CD4-, and CD8+ cells, natural killer (NK) cells, and mononuclear
      cells were determined by flow cytometry. The serum concentrations of interferon
      gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), interleukin 10 (IL
      10), and macrophage granulocyte-colony stimulating factor (GM-CSF) were
      determined. Pathological changes in different tissues from the experimentally
      infected pigs were recorded. RESULTS: The piglets in group 1 had the highest
      viral loads, the lowest antibody titers, the most-severe clinical signs, and the
      highest mortality (3/5, 60%; the mortality in the other groups was 0%), and
      interstitial pneumonia was more severe in this group compare to the other HP
      PRRSV infected groups. The serum levels of IFN-gamma, TNF-alpha, IL-10, and GM
      CSF varied (increased or decreased) most widely in group 1, as did each
      immunocyte subgroup. CONCLUSIONS: HP-PRRSV infection followed by PCV2 infection
      enhanced the replication of both viruses in the experimental piglets and led to
      more-severe clinical signs and lesions, indicating greater synergistic effects
      during the sequential infection of piglets with HP-PRRSV and then PCV2.

PMID- 23971712
TI  - Compression and contact area of anterior strut grafts in spinal instrumentation:
      a biomechanical study.
AB  - BACKGROUND: Anterior bone grafts are used as struts to reconstruct the anterior
      column of the spine in kyphosis or following injury. An incomplete fusion can
      lead to later correction losses and compromise further healing. Despite the
      different stabilizing techniques that have evolved, from posterior or anterior
      fixating implants to combined anterior/posterior instrumentation, graft
      pseudarthrosis rates remain an important concern. Furthermore, the need for
      additional anterior implant fixation is still controversial. In this bench-top
      study, we focused on the graft-bone interface under various conditions, using two
      simulated spinal injury models and common surgical fixation techniques to
      investigate the effect of implant-mediated compression and contact on the
      anterior graft. METHODS: Calf spines were stabilised with posterior internal
      fixators. The wooden blocks as substitutes for strut grafts were impacted using a
      "pressfit" technique and pressure-sensitive films placed at the interface between
      the vertebral bone and the graft to record the compression force and the contact
      area with various stabilization techniques. Compression was achieved either with
      posterior internal fixator alone or with an additional anterior implant. The
      importance of concomitant ligament damage was also considered using two simulated
      injury models: pure compression Magerl/AO fracture type A or rotation/translation
      fracture type C models. RESULTS: In type A injury models, 1 mm-oversized grafts
      for impaction grafting provided good compression and fair contact areas that were
      both markedly increased by the use of additional compressing anterior rods or by
      shortening the posterior fixator construct. Anterior instrumentation by itself
      had similar effects. For type C injuries, dramatic differences were observed
      between the techniques, as there was a net decrease in compression and an
      inadequate contact on the graft occurred in this model. Under these
      circumstances, both compression and the contact area on graft could only be
      maintained at high levels with the use of additional anterior rods. CONCLUSIONS:
      Under experimental conditions, we observed that ligamentous injury following type
      C fracture has a negative influence on the compression and contact area of
      anterior interbody bone grafts when only an internal fixator is used for
      stabilization. Because of the loss of tension banding effects in type C injuries,
      an additional anterior compressing implant can be beneficial to restore both
      compression to and contact on the strut graft.

PMID- 23971714
TI  - The effect of surgical wide excision and amniotic membrane transplantation with
      adjuvant topical mitomycin C treatment in recurrent conjunctival--corneal
      intraepithelial neoplasia.
AB  - PURPOSE: To investigate the effect of surgical wide excision and amniotic
      membrane transplantation with adjuvant mitomycin C 0.04% eye drops on recurrent
      conjunctival-corneal intraepithelial neoplasia (CCIN). METHODS: The authors
      applied amniotic membrane transplantation after total surgical excision of a
      tumor to a patient with recurrent conjunctival-corneal intraepithelial neoplasia.
      The tumor co-existed as a conjunctival lesion and corneal opacity. After one
      week, the patient received mitomycin C 0.04% eye drops four times a day for one
      month to prevent recurrence. Ocular complications and recurrence were evaluated
      under slit lamp microscopy for one year. RESULTS: Corneal epithelium completely
      healed within one week after the surgery. Both conjunctival and corneal lesions
      were completely regressed and no recurrence has been found with follow-up to 24
      months. CONCLUSIONS: Surgical wide excision and amniotic membrane transplantation
      with adjuvant topical MMC would be an effective treatment modality for treatment
      of recurrent CCIN.

PMID- 23971713
TI  - HIV and intestinal parasite co-infections among a Chinese population: an
      immunological profile.
AB  - BACKGROUND: Parasite infections often result in a switch of the human body's
      predominant immune reaction from T-helper 1 (Th1)-type to Th2-type. Hence,
      parasite infections are widely expected to accelerate the progression of human
      immunodeficiency virus (HIV) infections to acquired immunodeficiency syndrome
      (AIDS). In the People's Republic of China, both parasitic diseases and AIDS are
      epidemic in certain rural areas, and co-infections are relatively common.
      However, no population-based studies have yet investigated the frequency of HIV
      and parasite co-infections, and its effects on immune responses. We studied (1)
      the immune status of an HIV-infected population, and (2) the effect of co
      infection of HIV and intestinal parasites on selected parameters of the human
      immune system. METHODS: A total of 309 HIV-infected individuals were recruited
      and compared to an age-matched and sex-matched control group of 315 local HIV
      negative individuals. Questionnaires were administered to all participants to
      obtain information on sociodemographic characteristics, sanitation habits, family
      income, and recent clinical manifestations. Two consecutive stool samples and 10
      ml samples of venous blood were also collected from each individual for the
      diagnosis of parasite infections and quantitative measurements of selected
      cytokines and CD4+ T-lymphocytes, respectively. RESULTS: During the study period,
      79 HIV-infected individuals were not under highly active antiretroviral therapy
      (HAART) and were thus included in our analysis; the prevalence of intestinal
      helminth infections was 6.3% and that of protozoa was 22.8%. The most common
      protozoan infections were Blastocystis hominis (B. hominis) (13.9%) and
      Cryptosporidium spp. (10.1%). The prevalence of Cryptosporidium spp. in HIV
      infected individuals was significantly higher than that in HIV negative
      individuals (P < 0.05). Compared to the non-co-infected population, no
      significant difference was found for any of the measured immunological indicators
      (P > 0.05). However, the following trends were observed: IFN-gamma levels were
      lower, but the IL-4 level was higher, in the population co-infected with HIV and
      helminths. In the population co-infected with HIV and B. hominis, the IL-2 level
      was higher. The population co-infected with HIV and Cryptosporidium spp. had
      markedly lower CD4+ T-lymphocyte counts. CONCLUSION: According to the immunologic
      profile, co-infection with helminths is disadvantageous to HIV-infected
      individuals. It was associated with a shift in the Th1/Th2 balance in the same
      direction as that caused by the virus itself, which might indicate an
      acceleration of the progress from an HIV infection to AIDS. Co-infection with
      Cryptosporidium spp. was not associated with a significant change in immune
      factors but co-infection with Cryptosporidium spp. was associated with a reduced
      level of CD4 + T-lymphocytes, confirming the opportunistic nature of such
      infections. Co-infection with B. hominis, on the other hand, was associated with
      an antagonistic shift in the immunological profile compared to an HIV infection.

PMID- 23971715
TI  - Epiconjunctival mitomycin-C application for early failing filtering blebs.
AB  - PURPOSE: To evaluate the effectiveness of epiconjunctival Mitomycin-C (MMC)
      application in early failing filtering blebs. DESIGN: Interventional case series.
      PARTICIPANTS: Patients with failing blebs and raised intraocular pressure (IOP)
      in the early (two weeks to one month) postoperative period following glaucoma
      filtering surgery. METHODS: A retrospective analysis of records of failed blebs
      was done for the period of April 2011-March 2012. Patients who were subjected to
      three applications of MMC (0.04%) applied over the conjunctiva directly over the
      bleb at baseline (visit1), one week (visit 2) and at one month (visit 3) were
      included. Bleb characteristics were graded in a blinded fashion by one
      independent ophthalmologist, while IOP during follow-up visits were analyzed.
      MAIN OUTCOME MEASURES: Intraocular pressure, need for additional measure, or
      medications and bleb characteristics as graded by Indiana classification.
      RESULTS: Ten eyes of nine patients with failing blebs received topical MMC,
      including included eight males and one female with a mean age of 52 +/- 18 years
      (trabeculectomy:combined surgery = 5:5). Complete success was seen in eight of 10
      eyes with a final mean IOP of 14 +/- 2.9 mm Hg at three months. Excluding the two
      eyes that required medications, IOP reduction of 9%-42% was seen at visit 2, 16
      57% IOP reduction at visit 3, and 16-56% at three months' follow-up. Of eight
      eyes, all eyes showed decrease in vascularity of the blebs, p < 0.001. While the
      height of the blebs did not show significant increase, all had increase in the
      avascular area of the bleb. One eye developed spontaneously resolving adenoviral
      conjunctivitis without any sequelae. CONCLUSION: Three applications of
      epiconjunctival MMC may be a safe alternative for salvaging failing blebs in the
      early postoperative period. This may help maximize anti-fibrotic effect of MMC
      while minimizing complications by limiting the area of contact.

PMID- 23971716
TI  - Fatty acidomics: global analysis of lipid species containing a carboxyl group
      with a charge-remote fragmentation-assisted approach.
AB  - Charge-remote fragmentation has been well recognized as an effective approach for
      dissociation of long aliphatic chains. Herein, we exploited this approach for
      structural identification of all fatty acids including saturated, unsaturated,
      and modified ones by using electrospray ionization tandem mass spectrometry after
      one-step derivatization of a charge-carried reagent through an amidation
      reaction. We tested the approach with different charge-carried reagents with
      respect to the hydrophobicity, charge strength, and distance from the charge to
      the carboxyl group. We found that all of the derivatives with these reagents
      could yield informative charge-remote fragmentation patterns regardless of the
      different chemical and physical properties of the reagents. These informative
      fragmentation patterns all could be effectively used for structural elucidation
      of lipid species containing a carboxyl group. We further found that the
      distinguished charge-remote fragmentations of fatty acid isomers enabled us to
      determine the composition of these isomers without any chromatographic
      separation. Finally, the abundant fragments yielded from an individual
      derivatized moiety enabled us to sensitively quantify the individual species
      containing a carboxyl group. The described approach was a great extension to the
      multidimensional mass-spectrometry-based shotgun lipidomics for global analysis
      of fatty acids including isomers and modifications. We believe that this approach
      could greatly facilitate identification of the biochemical mechanisms underlying
      numerous pathological conditions. 

PMID- 23971717
TI  - PI3K-Akt/PKB signaling pathway in neutrophils and mononuclear cells exposed to N
      nitrosodimethylamine.
AB  - Neutrophils (PMN) play diverse regulatory and effector functions in the immune
      system through the release of reactive nitrogen species, including nitric oxide
      (NO). The enzyme responsible for NO synthesis in PMN is inducible nitric oxide
      synthase (iNOS) that is regulated by various signaling pathways, e.g. PI3K
      Akt/PKB, and transcription factors. N-Nitrosodimethylamine (NDMA), a xenobiotic
      widespread in the human environment, affects immune cells. The study objective
      here was to examine the role of the PI3K-Akt/PKB pathway in induction of NO
      synthesis (with involvement of iNOS) in human PMN, as well as in autologous
      mononuclear cells (PBMC), exposed to NDMA. Isolated cells were incubated for 2 h
      with a sub-lethal dose of NDMA and then the expression of several select proteins
      in the cell cytoplasmic and nuclear fractions were determined by Western blot
      analyses. The results indicated that NDMA enhanced expression of iNOS, phospho
      PI3K, and phospho-IkappaBalpha in the cytoplasmic fraction of the PMN and PBMC.
      The nuclear fraction of these cells also had a higher NF-kappaB expression.
      Moreover, in PMN, NDMA caused an increased expression of phospho-Akt (T308),
      phospho-Akt (S473), and phospho-IKKalphabeta in the cytoplasm, and c-Jun and FosB
      in the nuclear fraction. Blocking of PI3K caused a decrease in expression of all
      these proteins in NDMA-exposed PMN. However, inhibition of PI3K led to a drop in
      expression of iNOS, phospho-PI3K, and phospho-IkappaBalpha in the cytoplasm, and
      in NF-kappaB in the nuclear fraction, of PBMC. The results of these studies
      indicated to us that NDMA activates the PI3K-Akt/PKB pathway in human PMN and
      that this, in turn, contributes to the activation of transcription factors NF
      kappaB, c-Jun, and FosB involved in NO production (through modulation of iNOS
      expression).

PMID- 23971718
TI  - Suppression of NF-kappaB p65 nuclear translocation and tumor necrosis factor
      alpha by Pongamia pinnata seed extract in adjuvant-induced arthritis.
AB  - Pongamia pinnata is a plant known for its therapeutic usage in Indian traditional
      medicine. Despite the controversy regarding toxic flavonoid and erucic acid
      content, the seed of this plant is consumed in tribal medicine and its oil is
      used in Ayurveda to treat psoriasis and arthritis. This study explored the
      potential anti-arthritic effects of a P. pinnata seed (hexane) extract (PSE) at
      non-lethal doses in an adjuvant-induced arthritic rat model; possible mechanisms
      of any observed effects were also explored. After establishing the lethal doses
      arising from oral exposure to the extract, the material was administered per os
      daily at two doses (0.3 g/kg/day; 0.5 g/kg/day) to arthritic rats. Other rats
      received indomethacin or vehicle (control). Treatments were performed for a total
      of 14 days. One day after the final exposure, the rats were euthanized to permit
      harvest of various cells, blood, and tissues for analyses. Paw diameter and
      tissue myeloperoxidase activity in the paws were evaluated as indices for edema
      and neutrophil infiltration into the tissue. The severity of arthritis in the
      experimental rats was assessed via measures of urinary hydroxyproline (HP) and
      glucosamine, and of serum pro-inflammatory TNFalpha and anti-inflammatory IL-10.
      The extent of NF-kappaB p65 nuclear translocation in peritoneal macrophages
      harvested from naive rats and then treated in vitro was also assessed. The
      results indicated that exposure to PSE significantly decreased paw diameter,
      tissue myeloperoxidase level, and levels of urinary HP and glucosamine, as well
      as of serum TNFalpha and IL-10 in adjuvant-injected (arthritic) rats. In vitro
      PSE treatment also resulted in a marked inhibition of NF-kappaB p65 nuclear
      translocation in primary cultures of peritoneal macrophages. Thus, PSE appears to
      be able to prevent experimental arthritis, in part, by helping to maintain the
      balance between pro- and anti-inflammatory cytokines and by inhibiting NF-kappaB
      activation.

PMID- 23971719
TI  - Novel GATA1 mutation in residue D218 leads to macrothrombocytopenia and clinical
      bleeding problems.

PMID- 23971720
TI  - Berberis aristata/Silybum marianum fixed combination on lipid profile and insulin
      secretion in dyslipidemic patients.
AB  - BACKGROUND: Relatively large number of dietary supplements and nutraceuticals
      have been studied for their supposed or demonstrated ability to reduce
      cholesterolemia in humans. OBJECTIVES: The aim of this study was to evaluate the
      efficacy as antihypercholesterolemic and insulin-sensitizing agent of a
      combination of Berberis aristata/Silybum marianum extract (Berberol(r)) in a
      sample of dyslipidemic patients. A total of 102 dyslipidemic subjects were
      enrolled. After a 6 months run-in period of diet and physical activity, the
      patients were randomized to placebo or Berberis aristata/Silybum marianum extract
      588 mg/105 mg, twice a day for 3 months. Berberis aristata/Silybum marianum and
      placebo were then interrupted for 2 months (washout period), and then restarted
      for further 3 months. Anthropometric and metabolic parameters were assessed;
      moreover, all patients underwent a glucagon stimulation test. RESULTS: Berberis
      aristata/Silybum marianum reduced total cholesterol, triglycerides and low
      density lipoprotein cholesterol and increased high-density lipoprotein
      cholesterol after 3 months from randomization and compared to placebo group. When
      Berberis aristata/Silybum marianum was interrupted, lipid profile worsened, and
      it improved again when nutraceutical combination was reintroduced. During the
      glucagon stimulation test, a higher increase of C-peptide levels and a lower
      increase in glycemia after the test with Berberis aristata/Silybum marianum
      compared to placebo, to baseline and to randomization were recorded. No patients
      had serious adverse events in both groups. CONCLUSION: Berberis aristata/Silybum
      marianum is effective and safe in improving lipid profile and insulin secretion
      in euglycemic dyslipidemic patients.

PMID- 23971721
TI  - Enhancing the exposure of medical students to neurosurgery.

PMID- 23971722
TI  - Comparison of the efficacy and safety of low molecular weight heparins for venous
      thromboembolism prophylaxis in medically ill patients.
AB  - OBJECTIVE: To conduct a systematic review and mixed-treatment comparison (MTC)
      meta-analysis to compare the efficacy and safety of low molecular weight heparins
      (LMWHs) for venous thromboembolism (VTE) prophylaxis in hospitalized medically
      ill patients. As a secondary objective we compared all therapies within the
      network to each other. METHODS: We conducted a systematic literature search for
      randomized trials that evaluated pharmacologic VTE prophylaxis in hospitalized
      medically ill patients. We conducted a traditional meta-analysis for all pairwise
      comparisons using a random effects model, reporting relative risks (RRs) and 95%
      confidence intervals for each outcome. To determine the relative efficacy and
      safety of included therapies we conducted a MTC meta-analysis using a Bayesian
      framework, reporting odds ratios (OR) and 95% credible intervals. RESULTS: Twenty
      trials met inclusion criteria. Enoxaparin, dalteparin, nadroparin and certoparin
      were the LMWHs evaluated although none in direct comparative trials. Upon MTC,
      the relative efficacy of all LMWHs was similar in preventing mortality and VTE as
      well as in the odds of major and minor bleeding. Dalteparin was not included in
      the network to evaluate deep vein thrombosis (DVT) and pulmonary embolism (PE)
      due to lack of reported data and the remaining LMWHs were found to be similar in
      relative efficacy in preventing these outcomes. LIMITATIONS: Traditional meta
      analysis was not possible for many drug comparisons made within the MTC.
      Heterogeneity was observed in several of the traditional meta-analyses although
      this may be an inherent limitation of the studied population. Overall rarity of
      events contributed to imprecise estimates demonstrated by the wide confidence
      intervals. CONCLUSIONS: Enoxaparin, dalteparin, nadroparin and certoparin are
      similar in relative efficacy for the prevention of mortality and VTE and in the
      odds of major or minor bleeding while enoxaparin, nadroparin and certoparin are
      similar in relative efficacy for the prevention of PE and DVT in hospitalized
      medical patients.

PMID- 23971723
TI  - Osteochondroma as a cause of scapular winging in an adolescent: a case report and
      review of the literature.
AB  - INTRODUCTION: Winged scapula is defined as the prominence of the medial border of
      the scapula. The classic etiopathology of scapular winging are injuries to the
      spinal accessory or long thoracic nerves resulting respectively in trapezius and
      serratus anterior palsy. To the best of our knowledge, there are only few reports
      of scapular lesions being mistaken for winging of the scapula. We report a rare
      case of a large scapular osteochondroma arising from the medial border and
      causing a pseudowinging of the scapula. CASE PRESENTATION: A 17-year-old
      Caucasian boy came to us complaining about a winged left scapula. The patient had
      a complete painless range of motion, but a large hard bony swelling was palpable
      along the medial border of his left scapula. A grating sensation was felt when
      his arm was passively abducted and/or elevated causing discomfort. A lesion
      revealed on X-rays was diagnosed as an osteochondroma of the medial border of his
      scapula. After preoperative examinations, he underwent open surgery in order to
      remove the lesion. A histological examination confirmed the clinical diagnosis of
      osteochondroma. A clinical examination 3 months later showed a full and painless
      range of motion, the absence of the grating sensation during passive abduction
      and elevation and the complete disappearance of his left shoulder deformity.
      After 2 years of follow-up, there were no clinical or radiological signs of
      recurrence. CONCLUSIONS: Despite its rarity osteochondroma should be considered
      in the differential diagnosis for any adolescent presenting with a winging of the
      scapula.

PMID- 23971724
TI  - Clinicopathological investigation of lymph node metastasis predictors in
      superficial esophageal squamous cell carcinoma with a focus on evaluation of
      lympho-vascular invasion.
AB  - OBJECTIVE. Reliable indicators of the risk of lymph node metastasis (LNM) in
      superficial esophageal squamous cell carcinoma (sESCC: intramucosal and
      submucosal invasive carcinoma) may contribute to assist optimal clinical decision
      making for treating sESCC. In esophageal cancer, there is a possibility of
      metastasis, even in sESCC, and careful evaluation is needed when making a
      pathological diagnosis. In this study, we objectively evaluated predictive
      factors of LNM. MATERIALS AND METHODS. A total of 110 consecutive sESCC cases
      were obtained. We evaluated candidate predictive factors of LNM as follows: (1)
      maximum tumor diameter; (2) macroscopic type; (3) depth of tumor invasion; (4)
      histological differentiation; (5) infiltrative growth pattern; (6) tumor budding;
      (7) lymphatic invasion; (8) venous invasion and (9) lympho-vascular invasion
      (LVI). Both Elastica-Van Gieson staining (EVG) and immunohistochemistry (IHC: D2
      40, CD31, CD34) were used to evaluate invasion into the lympho-vascular spaces.
      For statistical analyses, single and multiple logistic regression were performed.
      RESULTS. LNM was observed in 37 cases (33.6%). LVI using EVG and IHC was the
      strongest independent predictor of LNM with an odds ratio of 12.01. Analysis of
      the relationship between LVI using EVG and IHC and LNM showed a negative
      predictive value of 94.6%. CONCLUSIONS. Evaluation of LVI using EVG and IHC may
      contribute to predict LNM in sESCC.

PMID- 23971725
TI  - Fate and toxicity of CuO nanospheres and nanorods used in Al/CuO nanothermites
      before and after combustion.
AB  - Although nanotechnology advancements should be fostered, the environmental health
      and safety (EHS) of nanoparticles used in technologies must be quantified
      simultaneously. However, most EHS studies assess the potential implications of
      the free nanoparticles which may not be directly applicable to the EHS of
      particles incorporated into in-use technologies. This investigation assessed the
      aquatic toxicological implications of copper oxide (CuO) nanospheres relative to
      CuO nanorods used in nanoenergetic applications to improve combustion. Particles
      were tested in both the as-received form and following combustion of a
      CuO/aluminum nanothermite. Results indicated nanospheres were more stable in
      water and slowly released ions, while higher surface area nanorods initially
      released more ions and were more toxic but generally less stable. After
      combustion, particles sintered into larger, micrometer-scale aggregates, which
      may lower toxicity potential to pelagic organisms due to deposition from water to
      sediment and reduced bioavailability after complexation with sediment organic
      matter. Whereas the larger nanothermite residues settled rapidly, implying lower
      persistence in water, their potential to release dissolved Cu was higher which
      led to greater toxicity to Ceriodaphnia dubia relative to parent CuO material
      (nanosphere or rod). This study illustrates the importance of considering the
      fate and toxicology of nanoparticles in context with their relevant in-use
      applications. 

PMID- 23971727
TI  - Metabolic pathways of T-2 toxin in in vivo and in vitro systems of Wistar rats.
AB  - In the present study, metabolites of T-2 toxin in in vivo and in vitro systems of
      Wistar rats were identified and elucidated by ultraperformance liquid
      chromatography-quadrupole/time-of-flight tandem mass spectrometry (UPLC-Q/TOF
      MS). Expected and unexpected metabolites were detected by Metabolynx(XS)
      software, which could automatically compare MS(E) data from the sample and
      control. A total of 19 metabolites of T-2 toxin were identified in this research,
      9 of them being novel, which were 15-deacetyl-T-2, 3'-OH-15-deacetyl-T-2, 3',7
      dihydroxy-T-2, isomer of 3',7-dihydroxy-T-2, 7-OH-HT-2, isomer of 7-OH-HT-2, de
      epoxy-3',7-dihydroxy-HT-2, 9-OH-T-2, and 3',9-dihydroxy-T-2. The results showed
      that the main metabolic pathways of T-2 toxin were hydrolysis, hydroxylation, and
      de-epoxidation. In addition, the results also revealed one novel metabolic
      pathway of T-2 toxin, hydroxylation at C-9 position, which was demonstrated by
      the metabolites 9-OH-T-2 and 3',9-dihydroxy-T-2. In addition, hydroxylation at C
      9 of T-2 toxin was also generated in in vitro of liver systems. Interestingly,
      several metabolites of hydroxylation at C-7 of T-2 toxin were also detected in in
      vivo male Wistar rats, but they were not found in in vivo female rats and in in
      vitro systems of Wistar rats. 

PMID- 23971726
TI  - Electrostatic control of peptide side-chain reactivity using amphiphilic
      homopolymer-based supramolecular assemblies.
AB  - Supramolecular assemblies formed by amphiphilic homopolymers with negatively
      charged groups in the hydrophilic segment have been designed to enable high
      labeling selectivity toward reactive side chain functional groups in peptides.
      The negatively charged interiors of the supramolecular assemblies are found to
      block the reactivity of protonated amines that would otherwise be reactive in
      aqueous solution, while maintaining the reactivity of nonprotonated amines.
      Simple changes to the pH of the assemblies' interiors allow control over the
      reactivity of different functional groups in a manner that is dependent on the
      pKa of a given peptide functional group. The labeling studies carried out in
      positively charged supramolecular assemblies and free buffer solution show that,
      even when the amine is protonated, labeling selectivity exists only when
      complementary electrostatic interactions are present, thereby demonstrating the
      electrostatically controlled nature of these reactions. 

PMID- 23971728
TI  - Voice use in professional soccer management.
AB  - Vocal load related to heavy voice use in particular professions increases the
      risk of occupational voice disorders. Research on professional voice use has
      primarily focused on educators, singers, and call-centre advisors. This paper
      describes the daily experiences of professional soccer managers' occupational
      voice use through qualitative methods. Four global themes were identified: 1)
      voice uses, 2) factors affecting voice change, 3) impact of voice use, and 4) the
      importance of voice in soccer management. All describe the nature of soccer
      managers' vocal demands. Risk factors for voice disorders include intense and
      prolonged voice use in environments with adverse acoustic properties for speakers
      and poor phonation methods. Research on vocal behaviours and early prevention
      programmes for this population group is warranted.

PMID- 23971729
TI  - Slow angled-descent forepaw grasping (SLAG): an innate behavioral task for
      identification of individual experimental mice possessing functional vision.
AB  - BACKGROUND: There is significant interest in the generation of improved assays to
      clearly identify experimental mice possessing functional vision, a property that
      could qualify mice for inclusion in behavioral and neuroscience studies. Widely
      employed current methods rely on mouse responses to visual cues in assays of
      reflexes, depth perception, or cognitive memory. However, commonly assessed mouse
      reflexes can sometimes be ambiguous in their expression, while depth perception
      assays are sometimes confounded by variation in anxiety responses and exploratory
      conduct. Furthermore, in situations where experimental groups vary in their
      cognitive memory capacity, memory assays may not be ideal for assessing
      differences in vision. RESULTS: We have optimized a non-invasive behavioral assay
      that relies on an untrained, innate response to identify individual experimental
      mice possessing functional vision: slow angled-descent forepaw grasping (SLAG).
      First, we verified that SLAG performance depends on vision and not olfaction.
      Next, all members of an age-ranged cohort of 158 C57BL/6 mice (57 wild-type, 101
      knockout, age range 44-241 days) were assessed for functional vision using the
      SLAG test without training or conditioning. Subjecting the population to a second
      innate behavioral test, Dark Chamber preference, corroborated that the functional
      vision assessment of SLAG was valid. CONCLUSIONS: We propose that the SLAG assay
      is immediately useful to quickly and clearly identify experimental mice
      possessing functional vision. SLAG is based on a behavioral readout with a
      significant innate component with no requirement for training. This will
      facilitate the selection of mice of known sighted status in vision-dependent
      experiments that focus on other types of behavior, neuroscience, and/or cognitive
      memory.

PMID- 23971730
TI  - Catalytic asymmetric Petasis reactions of vinylboronates.
AB  - Binaphthol-catalyzed asymmetric Petasis reactions of salicylaldehydes with
      dibutyl vinylboronates and secondary amines in the presence of 4 A molecular
      sieves (MS) afforded products with up to 99% ee in isolated yields of 39-94%. The
      99% ee of the product indicated that the reaction by the binaphthol-catalyzed
      pathway was roughly 500 times faster than the uncatalyzed pathway. NMR
      experiments ((1)H and (11)B) showed that the amine component played a role in
      triggering the reaction between the binaphthol catalyst and the vinylboronate in
      the catalytic reaction sequence. The 4 A MS enhanced both the rate and
      enantioselectivity by effective removal of water from the reaction system. A
      novel rearrangement reaction of the unconjugated allylic amine Petasis reaction
      product to a conjugated allylic amine was also observed. 

PMID- 23971731
TI  - Transcriptomic signatures in cartilage ageing.
AB  - INTRODUCTION: Age is an important factor in the development of osteoarthritis.
      Microarray studies provide insight into cartilage aging but do not reveal the
      full transcriptomic phenotype of chondrocytes such as small noncoding RNAs,
      pseudogenes, and microRNAs. RNA-Seq is a powerful technique for the interrogation
      of large numbers of transcripts including nonprotein coding RNAs. The aim of the
      study was to characterise molecular mechanisms associated with age-related
      changes in gene signatures. METHODS: RNA for gene expression analysis using RNA
      Seq and real-time PCR analysis was isolated from macroscopically normal cartilage
      of the metacarpophalangeal joints of eight horses; four young donors (4 years
      old) and four old donors (>15 years old). RNA sequence libraries were prepared
      following ribosomal RNA depletion and sequencing was undertaken using the
      Illumina HiSeq 2000 platform. Differentially expressed genes were defined using
      Benjamini-Hochberg false discovery rate correction with a generalised linear
      model likelihood ratio test (P < 0.05, expression ratios +/- 1.4 log2 fold
      change). Ingenuity pathway analysis enabled networks, functional analyses and
      canonical pathways from differentially expressed genes to be determined. RESULTS:
      In total, the expression of 396 transcribed elements including mRNAs, small
      noncoding RNAs, pseudogenes, and a single microRNA was significantly different in
      old compared with young cartilage (+/- 1.4 log2 fold-change, P < 0.05). Of these,
      93 were at higher levels in the older cartilage and 303 were at lower levels in
      the older cartilage. There was an over-representation of genes with reduced
      expression relating to extracellular matrix, degradative proteases, matrix
      synthetic enzymes, cytokines and growth factors in cartilage derived from older
      donors compared with young donors. In addition, there was a reduction in Wnt
      signalling in ageing cartilage. CONCLUSION: There was an age-related
      dysregulation of matrix, anabolic and catabolic cartilage factors. This study has
      increased our knowledge of transcriptional networks in cartilage ageing by
      providing a global view of the transcriptome.

PMID- 23971732
TI  - A novel role of the STAT3 pathway in brain inflammation-induced human neural
      progenitor cell differentiation.
AB  - Brain inflammation is a primary pathological driving force of many
      neurodegenerative disorders. In the destructive process, pro-inflammatory
      cytokines (IL-1beta and TNF-alpha), are robustly released, affecting normal
      neural progenitor cell (NPC) differentiation, and resulting in a vast number of
      astrocytes and a diminished neural population. A counteractive mechanism is still
      unknown. In this study, we have identified a link between brain inflammation and
      the signal transducer and activator of transcription 3 (STAT3) pathway: IL-1beta
      and TNF-alpha induce STAT3 activation in NPCs. Then to investigate STAT3's
      effects on NPC fate, we observed that an inhibition of STAT3 expression by siRNA
      inhibited astrocytic differentiation and increased neuronal differentiation of
      human NPCs in fetal bovine serum (FBS)-induced astrocyte differentiation
      condition. Furthermore, STAT3-targeting siRNA abrogated IL-1beta and TNF-alpha
      induced astrocyte differentiation and partially restored neuronal
      differentiation. Elimination of STAT3 expression also countered IL-1beta and TNF
      alpha-induced inhibition of proneural bHLH genes, mammalian achaete-schute
      homologue-1 (Mash1), Neurogenin1 (Ngn1), and Neurogenin2 (Ngn2). These data
      suggest that a suppression of STAT3 during brain inflammation would inhibit
      astrogliogenesis and promote neurogenesis. Thus, STAT3 could be a potential
      target of drug therapy for neurodegenerative disorders. 

PMID- 23971734
TI  - Roles of nicotinic acetylcholine receptors in stem cell survival/apoptosis,
      proliferation and differentiation.
AB  - The potential of stem cells in regenerative medicine, developmental biology, and
      drug discovery has been well documented. For example, stem cells have the
      extraordinary ability of self-renewal, and also give rise to many specialized
      cells. It is clear that stem cell technology has revolutionized our understanding
      of modern biology and medicine and provided new insights into the mechanisms
      controlling basic cell biology and various diseases. Nicotinic acetylcholine
      receptors (nAChRs) are prototypical members of the ligand-gated ion channel super
      family of neurotransmitter receptors that play many critical roles in brain and
      body function. It has been demonstrated that in addition to mediation of
      classical excitatory neurotransmission at some loci and modulation of release of
      neurotransmitters in some cases, nAChRs also play important roles in influencing
      synaptic architecture and plasticity as well as neuronal survival/death.
      Recently, emerging lines of evidence have suggested that nAChRs express on stem
      cells, where they likely mediate crucial effects of cholinergic signaling on stem
      cell survival/apoptosis, proliferation, differentiation and maturation. In this
      review, we summarize current development in cholinergic modulations of stem cell
      survival/apoptosis, proliferation and differentiation in order to evaluate the
      impact of nAChRs in stem cell biology and pathology. 

PMID- 23971733
TI  - Transgenic overproduction of omega-3 polyunsaturated fatty acids provides
      neuroprotection and enhances endogenous neurogenesis after stroke.
AB  - Strokes are devastating as there are no current therapies to prevent the long
      term neurological deficits that they cause. Soon after ischemic stroke, there is
      proliferation and differentiation of neural stem/progenitor cells as an important
      mechanism for neuronal restoration. However, endogenous neurogenesis by itself is
      insufficient for effective brain repair after stroke as most newborn neurons do
      not survive. One fascinating strategy for stroke treatment would thus be
      maintaining the survival and/or promoting the differentiation of endogenous
      neural stem/progenitor cells. Using transgenic (Tg) mice over-expressing the C.
      elegans fat-1 gene encoding an enzyme that converts endogenous omega-6 to omega-3
      polyunsaturated fatty acids (n-3 PUFAs), we showed that fat-1 Tg mice with
      chronically elevated brain levels of n-3 PUFAs exhibited less brain damage and
      significantly improved long-term neurological performance compared to wild type
      littermates. Importantly, post-stroke neurogenesis occurred more robustly in fat
      1 Tg mice after focal ischemia. This was manifested by enhanced neural stem cell
      proliferation/differentiation and increased migration of neuroblasts to the
      ischemic sites where neuroblasts matured into resident neurons. Moreover, these
      neurogenic effects were accompanied by significantly increased
      oligodendrogenesis. Our results suggest that n-3 PUFA supplementation is a
      potential neurogenic and oligodendrogenic treatment to naturally improve post
      stroke brain repair and long-term functional recovery. 

PMID- 23971735
TI  - Sevoflurane inhibits neurogenesis and the Wnt-catenin signaling pathway in mouse
      neural progenitor cells.
AB  - Recent population studies suggest that children who receive anesthesia and
      surgery could be at an increased risk for developing learning disabilities. The
      underlying reason for this clinical observation is largely unknown. Whether
      undergoing anesthesia contributes to learning disability development, or if the
      need for anesthesia and surgery is a marker for other unidentified factors that
      contribute to the development of learning disabilities, remains to be determined.
      Neurogenesis, regulated by the Wnt-catenin signaling pathway, has been shown to
      be involved in learning and memory, and sevoflurane is the most commonly used
      inhalation anesthetic in children. We therefore set out to determine the effects
      of sevoflurane on neurogenesis and the Wnt-catenin signaling pathway in mouse
      neural progenitor cells (NPCs) using immunofluorescence and Western blot
      analysis. Here we show for the first time that 4.1%, but not 2.0%, sevoflurane
      reduced mouse NPC proliferation, increased Glycogen synthase kinase-3beta(GSK
      3beta) levels, and decreased levels of beta-Catenin in mouse NPCs. The GSK-3beta
      inhibitor Lithium attenuated the sevoflurane-induced reduction in mouse NPC
      proliferation. The data suggest that sevoflurane may reduce neurogenesis through
      the Wnt-catenin signaling pathway. These findings would promote further studies
      to investigate the effects of anesthesia on neurogenesis and function of learning
      and memory, as well as the underlying mechanisms in vitro and in vivo. Ultimately
      these efforts would lead to safer anesthesia care and better postoperative
      outcomes in children. 

PMID- 23971736
TI  - Novel cerebellum-enriched miR-592 may play a role in neural progenitor cell
      differentiation and neuronal maturation through regulating Lrrc4c and Nfasc in
      rat.
AB  - MicroRNAs (miRNAs) are a class of small non-encoding RNAs that regulate gene
      expression at the posttranscriptional level. MiRNAs may characterize not only
      specific stages of the development of the neural cell population in CNS, but also
      distinct types of neural cells. However, the common pathways of the neural
      enriched miRNAs involved in neurogenesis of specific cell lineages remain poorly
      understood. In this report, in order to get insights into the common role of the
      miRNAs shared by cerebellum and forebrain, we studied the regulatory mechanism of
      neural enriched-miRNA in neural progenitor cell (NPCs) differentiation. Here, we
      identified a new cerebellum-enriched rno-miR-592 in rat cerebellum. It showed
      that rno-miR-592 was a neural enriched miRNA and may play an important role in
      rat embryonic neurogenesis or/and astrogliogenesis. We used both gain-of 
      function and loss-of -function approaches to demonstrate that rno-miR-592 could
      change the balance between neuron- and astrocyte- like differentiation and
      neuronal morphology. We observed that miR-592 could induce astrogliogenesis
      differentiation arrest or/and enhance neurogenesis in vitro. Meanwhile, silencing
      of miR-592 was not beneficial for neuronal maturation. We also identified Lrrc4c
      and Nfasc as miR-592 target genes, and miR-592 could affect the changes of Lrrc4c
      and Nfasc expression levels, suggesting that these two target genes may be
      involved in miR-592 regulative function in NPCs differentiation and neuronal
      maturation. Thus, we conclude that rno-miR-592 may affect the neural lineage
      differentiation via reducing astrogliogenesis or/and enhancing neurogenesis at
      least in part through regulating its target genes Lrrc4c and Nfasc in vitro.
      Together, we report here for the first time the important role of miR-592 in rat
      NPCs differentiation and neuronal maturation. 

PMID- 23971737
TI  - Subretinal transplantation of rat MSCs and erythropoietin gene modified rat MSCs
      for protecting and rescuing degenerative retina in rats.
AB  - For degenerative retinal diseases, like the acquired form exemplified by age
      related macular degeneration (AMD), there is currently no cure. This study was to
      explore a stem cell therapy and a stem cell based gene therapy for sodium iodate
      (SI)-induced retinal degeneration in rats. Three cell types, i.e., rat
      mesenchymal stem cells (rMSCs) alone, erythropoietin (EPO) gene modified rMSCs
      (EPO-rMSCs) or doxycycline (DOX) inducible EPO expression rMSCs (Tet-on EPO
      rMSCs), were transplanted into the subretinal spaces of SI-treated rats. The
      rMSCs were prepared for transplantation after 3 to 5 passages or modified with
      EPO gene. During the 8 weeks after the transplantation, the rats treated with
      rMSCs alone or with two types of EPO-rMSCs were all monitored with fundus
      examination, fundus fluorescein angiography (FFA) and electroretinogram. The
      transplantation efficiency of donor cells was examined for their survival,
      integration and differentiation. Following the transplantation, labeled donor
      cells were observed in subretinal space and adopted RPE morphology. EPO
      concentration in vitreous and retina of SI-treated rats which were transplanted
      with EPO-rMSCs or Tet-on EPO-rMSCs was markedly increased, in parallel with the
      improvement of retinal morphology and function. These findings suggest that rMSCs
      transplantation could be a new therapy for degenerative retinal diseases since it
      can protect and rescue RPE and retinal neurons, while EPO gene modification to
      rMSCs could be an even better option. 

PMID- 23971738
TI  - Road to future: iPSC clinical application in Parkinson's disease treatment.
AB  - Cell-replacement therapy using Parkinson's disease (PD) specific induced
      pluripotent stem cell (iPSC) holds great promise in treating PD. However, the
      problem of iPSC safety and efficiency restrict its clinical application.
      Meanwhile the requirement of skin biopsy for fibroblast will increase the risk of
      complication. In the past few years, the advances of iPSC technology in
      efficiency, cell resource, safety and cell culture have made it possible to use
      the derivatives of iPSCs to clinical PD treatment. This review will summarize
      these progresses of iPSC technique in this fast-moving community. 

PMID- 23971739
TI  - Diagnosing heterogeneous dynamics in single-molecule/particle trajectories with
      multiscale wavelets.
AB  - We describe a simple automated method to extract and quantify transient
      heterogeneous dynamical changes from large data sets generated in single
      molecule/particle tracking experiments. Based on wavelet transform, the method
      transforms raw data to locally match dynamics of interest. This is accomplished
      using statistically adaptive universal thresholding, whose advantage is to avoid
      a single arbitrary threshold that might conceal individual variability across
      populations. How to implement this multiscale method is described, focusing on
      local confined diffusion separated by transient transport periods or hopping
      events, with three specific examples: in cell biology, biotechnology, and glassy
      colloid dynamics. The discussion is generalized within the framework of
      continuous time random walk. This computationally efficient method can run
      routinely on hundreds of millions of data points analyzed within an hour on a
      desktop personal computer. 

PMID- 23971740
TI  - Evaluating hormonal mechanisms of vitamin D receptor agonist therapy in diabetic
      kidney disease: the VALIDATE-D study.
AB  - BACKGROUND: Insufficient vitamin D status and increased renin-angiotensin system
      (RAS) activity have been associated with renal-vascular disease and nephropathy
      in diabetes. Accumulating evidence indicates that vitamin D receptor (VDR)
      activation lowers unfavorable RAS activity; however, more human intervention
      studies evaluating whether this mechanism could influence diabetic kidney disease
      are needed. We previously reported that both vitamin D levels and genetic
      variation at the VDR predict human RAS activity, and that vitamin D therapy can
      lower RAS activity in non-diabetics. The VALIDATE-D study is a randomized,
      placebo-controlled, intervention study designed to extend these findings by
      evaluating whether direct VDR activation in diabetes lowers circulating and local
      renal-vascular tissue RAS activity (Aims 1 and 2) in a manner similar to the
      action of ACE inhibitors (Aim 3). METHODS/DESIGN: Forty subjects with type 2
      diabetes, microalbuminuria, and without chronic kidney disease will be recruited
      to undergo detailed assessment of the RAS before and after randomization to
      calcitriol 0.75 mcg/day or placebo. Primary analyses will evaluate whether
      calcitriol therapy reduces circulating and renal-vascular tissue-RAS activity in
      comparison to placebo. All subjects will thereafter be treated with lisinopril
      and followed for 3.5 months to evaluate whether combination therapy (calcitriol +
      lisinopril vs. placebo + lisinopril) additively or synergistically improves renal
      vascular function, and lowers proteinuria. DISCUSSION: The VALIDATE-D study is
      the first human intervention study to evaluate whether direct VDR activation can
      lower the human RAS in diabetes, compared to the effect of an ACE inhibitor, and
      whether this mechanism can translate to clinically relevant endpoints for
      diabetic kidney disease. The outcomes of VALIDATE-D will have major implications
      for the recommendation of vitamin D supplementation for the primary prevention of
      kidney complications in diabetes. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT01635062.

PMID- 23971741
TI  - Formation of carboxy- and amide-terminated alkyl monolayers on Silicon(111)
      investigated by ATR-FTIR, XPS, and X-ray scattering: construction of
      photoswitchable surfaces.
AB  - We have prepared high-quality, densely packed, self-assembled monolayers (SAMs)
      of carboxy-terminated alkyl chains on Si(111). The samples were made by thermal
      grafting of methyl undec-10-enoate under an inert atmosphere and subsequent
      cleavage of the ester functionality to disclose the carboxylic acid end-group. X
      ray photoelectron spectroscopy (XPS) and grazing incidence X-ray diffraction
      (GIXD) indicate a surface coverage of about 50% of the initially H-terminated
      sites. In agreement, GIXD implies a rectangular unit mesh of 6.65 and 7.68 A side
      lengths, containing two molecules in a regular zigzag-like substitution pattern
      for the ester- and carboxy-terminated monolayer. Hydrolysis of the remaining H
      Si(111) bonds at the surface furnished HO-Si(111) groups according to XPS and
      attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR)
      studies. The amide-terminated alkyl SAM on Si(111) assembled in a 2-(6-chloro-1H
      benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU)-mediated
      one-pot coupling reaction under an inert atmosphere, whereby the active ester
      forms in situ prior to the reaction with an amino-functionalized photoswitchable
      fulgimide. ATR-FTIR and XPS studies of the fulgimide samples revealed closely
      covered amide-terminated SAMs. Reversible photoswitching of the headgroup was
      read out by applying XPS, ATR-FTIR, and difference absorption spectra in the mid
      IR. In XPS, we observed a reversible breathing of the amide/imide C1s and N1s
      signals of the fulgimide. The results demonstrate the general suitability of HCTU
      as a reagent for amide couplings to carboxy-terminated alkyl SAMs and the on-chip
      functionalization toward photoswitchable Si(111) surfaces. 

PMID- 23971742
TI  - Urethral pressure reflectometry, a novel technique for simultaneous recording of
      pressure and cross-sectional area in the prostatic urethra: testing in men
      without bothersome lower urinary tract symptoms.
AB  - OBJECTIVE: Urethral pressure reflectometry (UPR) was introduced in 2005, for
      simultaneous measurement of pressure and cross-sectional area in the female
      urethra. It has shown to be more reproducible than conventional pressure
      measurement. Recently, it has been tested in the anal canal and the prostatic
      urethra. The primary aim of this study was to describe UPR in men without
      bothersome lower urinary tract symptoms. MATERIAL AND METHODS: The study
      investigated 18 men, median age 59 (range 50-77) with UPR and pressure-flow
      analyses (PQ), the International Prostate Symptom Score and the Danish version of
      Prostate Symptom Score, flow rate, residual urine measurements, transrectal
      ultrasound, urethral pressure profilometry and visual analogue scale
      (Discomfort). UPR parameters measured were opening and closing pressure, opening
      and closing elastance and hysteresis, from the bladder neck to the sphincter
      region. RESULTS: All UPR parameters increased significantly from the bladder neck
      to the sphincter region, except for the opening pressure between the prostate and
      the sphincter region. Seven men were obstructed according to PQ, but with no
      significant differences in any other standard urodynamic parameters. The
      hysteresis in the sphincter region was significantly lower in the obstructed
      group (p = 0.005). Discomfort was significantly lower with PQ compared to UPR (p
      = 0.04). Nine men had slight bleeding from the urethra during measurement with
      UPR. CONCLUSIONS: The increase in all parameters from the bladder neck to the
      sphincter region is consistent with previous studies measuring the same
      parameters. The hysteresis may explain why seven men were obstructed according to
      PQ.

PMID- 23971743
TI  - The biosynthesis and biological function of diphthamide.
AB  - Eukaryotic and archaeal elongation factor 2 contains a unique post
      translationally modified histidine residue, named diphthamide. Genetic and
      biochemical studies have revealed that diphthamide biosynthesis involves a multi
      step pathway that is evolutionally conserved among lower and higher eukaryotes.
      During certain bacterial infections, diphthamide is specifically recognized by
      bacterial toxins, including diphtheria toxin, Pseudomonas exotoxin A and cholix
      toxin. Although the pathological relevance is well studied, the physiological
      function of diphthamide is still poorly understood. Recently, many new
      interesting developments in understanding the biosynthesis have been reported.
      Here, we review the current understanding of the biosynthesis and biological
      function of diphthamide.

PMID- 23971745
TI  - Defining predictive values using three different platelet function tests for
      CYP2C19 phenotype status on maintenance dual antiplatelet therapy after PCI.
AB  - Published data suggests that the presence of CYP2C19*2 or *3 loss of function
      (LOF) alleles is indicative of increased platelet aggregation and a higher risk
      of adverse cardiovascular events after clopidogrel administration. We sought to
      determine cut-off values using three different assays for prediction of the
      CYP2C19 phenotype in Korean percutaneous coronary intervention (PCI) patients. We
      enrolled 244 patients with drug-eluting stent implantation who were receiving
      clopidogrel and aspirin maintenance therapy for one month or more. Platelet
      reactivity was assessed with light transmittance aggregometry (LTA), multiple
      electrode aggregometry (MEA) and the VerifyNow P2Y12 assay (VN). The CYP2C19
      genotype was analyzed by polymerase chain reaction (PCR) and snapshot method. The
      frequency of CYP2C19 LOF allele carriers was 58.6%. The cut-off values from LTA,
      MEA and VerifyNow for the identification of LOF allele carriers were as follows:
      10 uM ADP-induced LTA >= 48 %, VN>242 PRU and MEA >= 37 U. Between the three
      tests, correlation was higher between LTA vs. VN assays (r=0.69) and LTA vs. MEA
      (r=0.56), with moderate agreement (kappa=0.46 and kappa=0.46), but between VN
      assay and MEA, both devices using whole blood showed a lower correlation (r=0.42)
      and agreement (kappa=0.3). Our results provide guidance regarding cut-off levels
      for LTA, VerifyNow and MEA assays to detect the CYP2C19 LOF allele in patients
      during dual antiplatelet maintenance therapy.

PMID- 23971744
TI  - Sensitive, simultaneous quantitation of two unlabeled DNA targets using a
      magnetic nanoparticle-enzyme sandwich assay.
AB  - We report herein the development of a simple, sensitive colorimetric magnetic
      nanoparticle (MNP)-enzyme-based DNA sandwich assay that is suitable for
      simultaneous, label-free quantitation of two DNA targets down to 50 fM level. It
      can also effectively discriminate single-nucleotide polymorphisms (SNPs) in genes
      associated with human cancers (KRAS codon 12/13 SNPs). This assay uses a pair of
      specific DNA probes, one being covalently conjugated to an MNP for target capture
      and the other being linked to an enzyme for signal amplification, to sandwich a
      DNA target, allowing for convenient magnetic separation and subsequent efficient
      enzymatic signal amplification for high sensitivity. Careful optimization of the
      MNP surfaces and assay conditions greatly reduced the background, allowing for
      sensitive, specific detection of as little as 5 amol (50 fM in 100 MUL) of target
      DNA. Moreover, this sensor is robust, it can effectively discriminate cancer
      specific SNPs against the wild-type noncancer target, and it works efficiently in
      10% human serum. Furthermore, this sensor can simultaneously quantitate two
      different DNA targets by using two pairs of unique capture- and signal-DNA probes
      specific for each target. This general, simple, and sensitive DNA sensor appears
      to be well-suited for a wide range of genetics-based biosensing and diagnostic
      applications. 

PMID- 23971746
TI  - Does the level of bacterial exposure in early life impact the risk of Type 1
      diabetes?

PMID- 23971747
TI  - Can vitamin D intake during pregnancy affect the risk of allergy in children?

PMID- 23971749
TI  - Food protein-induced enterocolitis syndrome, from practice to theory.
AB  - Food protein-induced enterocolitis syndrome (FPIES) is an allergic disease,
      probably non-IgE-mediated, with expression predominantly in the GI tract. The
      most characteristic symptom is repeated, debilitating vomiting. It occurs 2-6 h
      after ingestion of culprit food and is usually accompanied by pallor and
      lethargy. There may be diarrhea, and in 10-20% of cases, severe hypotension.
      These symptoms resolve completely within a few hours. The food most frequently
      involved is cow's milk, followed by rice, but many other foods may be involved.
      The prognosis is generally good in a few years. In this review the authors try to
      cope, with the help of some case histories, with the practical clinical aspects
      of FPIES. The authors also try to provide a management approach based on current
      knowledge, and finally, to point out the aspects of FPIES that are still
      controversial. 

PMID- 23971750
TI  - Nutrigenetics, nutrigenomics and inflammatory bowel diseases.
AB  - Inflammatory bowel disease includes ulcerative colitis and Crohn's disease, which
      are both inflammatory disorders of the gastrointestinal tract. Both types of
      inflammatory bowel disease have a complex etiology, resulting from a genetically
      determined susceptibility interacting with environmental factors, including the
      diet and gut microbiota. Genome Wide Association Studies have implicated more
      than 160 single-nucleotide polymorphisms in disease susceptibility. Consideration
      of the different pathways suggested to be involved implies that specific dietary
      interventions are likely to be appropriate, dependent upon the nature of the
      genes involved. Epigenetics and the gut microbiota are also responsive to dietary
      interventions. Nutrigenetics may lead to personalized nutrition for disease
      prevention and treatment, while nutrigenomics may help to understand the nature
      of the disease and individual response to nutrients. 

PMID- 23971751
TI  - Immunological and molecular basis of nonalcoholic steatohepatitis and
      nonalcoholic fatty liver disease.
AB  - The prevalence of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic
      steatohepatitis (NASH) is rising worldwide with the increasing incidence of
      obesity, Type 2 diabetes mellitus and metabolic syndrome. NASH is currently one
      of the most common indications of liver transplantation in the United States. The
      immune system plays a major role in the pathogenesis of NAFLD/NASH. The metabolic
      changes, associated with obesity and metabolic syndrome, induce immunological
      responses resulting in NAFLD and further aggravation of the metabolic derangement
      in a feed-forward loop. Genetic and endocrine factors modulate the immunological
      and metabolic responses and determine the pathophysiological features of NAFLD.
      Histologically, NAFLD is a spectrum that ranges from simple hepatic steatosis to
      severe steatohepatitis, liver cirrhosis and/or hepatocellular carcinoma. Liver
      cirrhosis and hepatocellular carcinoma are responsible for the morbidity and
      mortality of the disease. This article is a critical evaluation of our current
      knowledge of the immunological and molecular basis of the disease. 

PMID- 23971752
TI  - The alarmin functions of high-mobility group box-1 and IL-33 in the pathogenesis
      of systemic lupus erythematosus.
AB  - 'Alarmins' are a group of endogenous proteins or molecules that are released from
      cells during cellular demise to alert the host innate immune system. Two of them,
      high-mobility group box-1 (HMGB1) and IL-33 shared many similarities of cellular
      localization, functions and involvement in various inflammatory diseases
      including systemic lupus erythematosus (SLE). The expressions of HMGB1 and IL-33,
      and their corresponding receptors RAGE (receptor for advanced glycation end
      products) and ST2, respectively, are substantially upregulated in patients with
      lupus nephritis (LN). This review highlights the emerging roles of alarmin
      proteins in various pathologies of LN, by focusing on classical HMGB1 and a newly
      discovered alarmin IL-33. 

PMID- 23971753
TI  - Role of vitamin D in the pathogenesis and treatment of atopic dermatitis.
AB  - Atopic dermatitis (AD) is a highly prevalent allergic skin disease that affects
      children worldwide. Epidemiological, clinical and basic immunological studies
      have suggested an association between vitamin D (VD) deficiency and the
      development of AD and other allergic diseases. Low levels of VD, a pleiotropic
      hormone that has widespread effects on the immune system and skin integrity,
      appear to be inversely correlated with AD severity, and VD deficiency at birth is
      associated with higher risk of developing AD. Recent randomized trials have
      reported inconsistent, but still promising, results on whether VD supplementation
      may improve AD severity. The apparent differences are likely due to small
      samples, different regimens and different patient populations. The mechanisms
      underlying this potential improvement in AD severity remain under investigation. 

PMID- 23971754
TI  - B-cell-targeted therapies in systemic lupus erythematosus and ANCA-associated
      vasculitis: current progress.
AB  - B cells play a central role in the pathogenesis of systemic lupus erythematosus
      and anti-neutrophil cytoplasmic antibody-associated vasculitis. There are various
      strategies for targeting B cells including depletion, inhibition of survival
      factors, activation and inhibition of co-stimulatory molecules. Controlled trials
      in systemic lupus erythematosus have shown positive results for belimumab,
      promising results for epratuzumab and negative results for rituximab. The failure
      of rituximab in controlled trials has been attributed to trial design, sample
      size and outcome measures rather than true inefficacy. In anti-neutrophil
      cytoplasmic antibody-associated vasculitis, rituximab is effective for remission
      induction and in relapsing disease. However, the optimal long-term re-treatment
      strategy remains to be determined. Over the next 5 years, evidence will be
      available regarding the clinical efficacy of these novel therapies, biomarkers
      and their long-term safety. 

PMID- 23971755
TI  - Assessing immunologic risk factors in transplantation.
AB  - The innate and adaptive immune systems, together, represent the largest
      impediment to good and long-lasting graft function. Although improved
      immunosuppressive agents and expanded and enhanced diagnostic tools have led to
      better prevention and treatment of acute rejection, chronic rejection remains a
      serious threat to long-term graft survival. Immunologic heterogeneity among
      patients, variability in treatment protocols and unforeseen events following
      transplantation translate into different levels of risk among patients. While one
      cannot predict with certainty the short- and long-term outcomes of a particular
      transplant, it is possible to identify immunologic risk factors that can affect
      outcome. 

PMID- 23971756
TI  - Impact of mTOR-I on fertility and pregnancy: state of the art and review of the
      literature.
AB  - Successful transplantation should lead to improvements in sexual function and sex
      hormone disturbances in both men and women, but immunosuppressive drugs may
      interfere with hormone metabolism. In this regard, several studies have showed a
      potential negative effect of mTOR inhibitors (mTORi) on male gonadal function,
      while their role in the female patients is not well documented in the literature.
      Successful pregnancy is possible after solid organ transplantation. The fetal
      effects of mTORi are still poorly defined but they seem not to represent an
      absolute contraindication for pregnancy. The aim of our study would be to review
      the impact of mTORi on fertility and pregnancy in order to have a clearer picture
      about their possible use after organ transplantation. 

PMID- 23971757
TI  - Higher fetuin-A level is associated with coexistence of elevated alanine
      aminotransferase and the metabolic syndrome in the general population.
AB  - BACKGROUND: Higher fetuin-A levels have been linked to fatty liver disease (FLD),
      the most common cause of elevated alanine aminotransferase (ALT) levels, but
      associations between ALT and fetuin-A level have been inconsistent. The presence
      of the metabolic syndrome in individuals with elevated ALT levels has been shown
      to characterize more severe FLD. Thus, aim of the study was to investigate the
      association between fetuin-A level and the coexistence of elevated ALT levels and
      metabolic syndrome (ALT-MetS). METHODS: A population-based cross-sectional study
      including 728 individuals (age 50-77 years) was conducted. We used multivariable
      logistic regression analysis to assess the association between serum fetuin-A
      level and the dichotomous outcome ALT-MetS, defined as coexistence of elevated
      ALT level (>75th percentile) and metabolic syndrome (any three of the components:
      abdominal obesity, elevated triglycerides, reduced high-density lipoprotein
      cholesterol, elevated blood pressure, abnormal glucose metabolism). RESULTS:
      Individuals with a high fetuin-A level had an odds ratio (OR) for ALT-MetS of
      2.22 [95% confidence interval (CI) 1.36-3.63; Ptrend=<0.001] comparing extreme
      tertiles. After excluding individuals with cancer, stroke, or myocardial
      infarction, individuals with high fetuin-A levels had an OR for ALT-MetS of 2.48
      (95% CI 1.38-4.47) comparing extreme tertiles, and we observed statistical
      interaction between fetuin-A level and age (P=0.048). Fetuin-A level was
      associated with ALT-MetS in young individuals, defined as <64 years of age (OR
      3.30, 95% CI 1.45-7.55; Ptrend=0.004), and not statistically significant in older
      individuals (OR 1.79, 95% CI 0.74-4.31; Ptrend=0.197). CONCLUSIONS: Fetuin-A
      level was positively associated with ALT-MetS, particularly in younger
      individuals. Prospective studies in larger populations are warranted.

PMID- 23971758
TI  - Non-targeted analysis of petroleum metabolites in groundwater using GC*GC-TOFMS.
AB  - Groundwater at fuel release sites often contains nonpolar hydrocarbons that
      originate from both the fuel release and other environmental sources, as well as
      polar metabolites of petroleum biodegradation. These compounds, along with other
      polar artifacts, can be quantified as "total petroleum hydrocarbons" using USEPA
      Methods 3510/8015B, unless a silica gel cleanup step is used to separate nonpolar
      hydrocarbons from polar compounds prior to analysis. Only a limited number of
      these metabolites have been identified by traditional GC-MS methods, because they
      are difficult to resolve using single-column configurations. Additionally, the
      targeted use of derivatization limits the detection of many potential metabolites
      of interest. The objective of this research was to develop a nontargeted GC*GC
      TOFMS approach to characterize petroleum metabolites in environmental samples
      gathered from fuel release sites. The method tentatively identified more than 760
      unique polar compounds, including acids/esters, alcohols, phenols, ketones, and
      aldehydes, from 22 groundwater samples collected at five sites. Standards for 28
      polar compounds indicate that effective limits of quantitation for most of these
      compounds in the groundwater samples range from 1 to 11 MUg/L. 

PMID- 23971759
TI  - Recurrent arterial and venous thrombosis in a 16-year-old boy in the course of
      primary antiphospholipid syndrome despite treatment with low-molecular-weight
      heparin: a case report.
AB  - INTRODUCTION: Antiphospholipid syndrome is a multisystem autoimmune disease
      characterized by arterial and/or venous thrombosis and persistent presence of
      antiphospholipid antibodies. It can be a primary disease or secondary when
      associated with other autoimmune diseases. CASE PRESENTATION: We present a case
      of a 16-year-old Caucasian boy with a massive arterial and venous thrombosis in
      his lower limbs as well as in his central nervous system with clinical symptoms
      such as headaches and chorea. He did not present any clinical or laboratory signs
      of a systemic inflammatory connective tissue disease, including systemic lupus
      erythematosus. Based on the clinical picture and results of the diagnostic tests
      (positive antibodies against beta2-glycoprotein and a high titre of
      anticardiolipin antibodies) we finally diagnosed primary antiphospholipid
      syndrome. During a 9-month follow up after the acute phase of the disease, he was
      treated with low-molecular-weight heparin. Neurological symptoms were relieved.
      Features of recanalization in the vessels of his lower limbs were observed. After
      a subsequent 6 months, because of the failure of preventive treatment - an
      incident of thrombosis of the vessels of his testis - treatment was modified and
      heparin was replaced with warfarin. CONCLUSION: Although the preventive treatment
      with warfarin in our patient has continued for 1 year of follow up without new
      symptoms, further observation is needed.

PMID- 23971760
TI  - Rapid fecal calprotectin correlates with clinical and endoscopic severity of
      inflammatory bowel diseases.

PMID- 23971761
TI  - Acute respiratory failure from Surgifoam expansion after anterior cervical
      surgery: case report.
AB  - A 65-year-old woman underwent an uneventful C3-4 anterior cervical discectomy and
      fusion for a large, symptomatic disc herniation. On postoperative Day 1 the
      patient suffered a sudden, acute respiratory compromise. Emergency fiberoptic
      intubation revealed significant anterior neck swelling with concern for physical
      obstruction of the airway. Computed tomography of the neck did not demonstrate an
      expanding hematoma. The patient was managed with surgical wound exploration and
      washout. Examination of the anterior neck after incision of the prior surgical
      site revealed a large volume of Surgifoam under high pressure, which was greater
      than the amount used during the initial surgery. Thorough washout of the surgical
      site did not reveal any swelling of the prevertebral soft tissues or hematoma,
      and the Hemovac drain did not appear to be occluded. The patient was extubated on
      the 2nd postoperative day and is symptom free 12 months after surgery. To the
      authors' knowledge, this report represents the first reported complication of
      acute respiratory failure from Surgifoam overexpansion after anterior cervical
      surgery. 

PMID- 23971762
TI  - Tumor control after surgery for spinal myxopapillary ependymomas: distinct
      outcomes in adults versus children: a systematic review.
AB  - OBJECT: Myxopapillary ependymomas (MPEs) are rare WHO Grade I tumors found in the
      conus medullaris, cauda equina, and filum terminale. Treatment generally consists
      of resection with or without adjuvant radiotherapy. Evidence-based guidelines for
      surgical management are lacking due to the rarity of this tumor. METHODS: An
      English-language PubMed search was performed using the key words "myxopapillary"
      and "ependymoma." Reports describing fewer than 3 patients or those lacking data
      on the extent of resection or radiotherapy were excluded. A total of 28 articles
      describing 475 patients met the authors' inclusion criteria. Patients were
      grouped by extent of resection and whether or not they underwent adjuvant
      radiotherapy. Differences in recurrence rates were assessed by chi-square test.
      RESULTS: The overall recurrence rate was 15.5% in patients treated by gross-total
      resection (GTR) and 32.6% in patients treated by subtotal resection (STR),
      irrespective of whether they underwent adjuvant therapy (p < 0.001). Regardless
      of the extent of resection, adjuvant radiotherapy was not associated with a
      decrease in recurrence rates. The overall recurrence rate was 15.6% in patients
      who underwent GTR and radiotherapy compared with 15.9% in patients who underwent
      GTR alone (p = 0.58), and it was 29.3% in patients who underwent STR and
      radiotherapy compared with 35.1% in those who underwent STR alone (p = 0.53). The
      difference between recurrence rates for patients who underwent GTR alone versus
      STR and radiotherapy was statistically significant (p = 0.02). Subgroup analysis
      demonstrated significantly higher recurrence rates in pediatric patients compared
      with adults (40.5% vs 23.4%, respectively; p = 0.02). Even in the setting of GTR
      alone, recurrence rates were higher in pediatric patients (65% vs 7.6%; p <
      0.001). CONCLUSIONS: Gross-total resection alone is associated with decreased
      recurrence rates compared with STR with or without radiotherapy. The authors'
      results suggest that treatment goals should include attempted GTR whenever
      possible. The observation that children benefitted from radiation therapy to a
      greater extent than did adults suggests that biological differences between
      tumors in these patient populations warrants more rigorous scientific studies.

PMID- 23971763
TI  - Reoperation rates and impact on outcome in a large, prospective, multicenter,
      adult spinal deformity database: clinical article.
AB  - OBJECT: Complications and reoperation for surgery to correct adult spinal
      deformity are not infrequent, and many studies have analyzed the rates and
      factors that influence the likelihood of reoperation. However, there is a need
      for more comprehensive analyses of reoperation in adult spinal deformity surgery
      from a global standpoint, particularly focusing on the 1st year following
      operation and considering radiographic parameters and the effects of reoperation
      on health-related quality of life (HRQOL). This study attempts to determine the
      prevalence of reoperation following surgery for adult spinal deformity, assess
      the indications for these reoperations, evaluate for a relation between specific
      radiographic parameters and the need for reoperation, and determine the potential
      impact of reoperation on HRQOL measures. METHODS: A retrospective review was
      conducted of a prospective, multicenter, adult spinal deformity database
      collected through the International Spine Study Group. Data collected included
      age, body mass index, sex, date of surgery, information regarding complications,
      reoperation dates, length of stay, and operation time. The radiographic
      parameters assessed were total number of levels instrumented, total number of
      interbody fusions, C-7 sagittal vertical axis, uppermost instrumented vertebra
      (UIV) location, and presence of 3-column osteotomies. The HRQOL assessment
      included Oswestry Disability Index (ODI), 36-Item Short Form Health Survey
      physical component and mental component summary, and SRS-22 scores. Smoking
      history, Charlson Comorbidity Index scores, and American Society of
      Anesthesiologists Physical Status classification grades were also collected and
      assessed for correlation with risk of early reoperation. Various statistical
      tests were performed for evaluation of specific factors listed above, and the
      level of significance was set at p < 0.05. RESULTS: Fifty-nine (17%) of a total
      of 352 patients required reoperation. Forty-four (12.5%) of the reoperations
      occurred within 1 year after the initial surgery, including 17 reoperations (5%)
      within 30 days. Two hundred sixty-eight patients had a minimum of 1 year of
      follow-up. Fifty-three (20%) of these patients had a 3-column osteotomy, and 10
      (19%) of these 53 required reoperation within 1 year of the initial procedure.
      However, 3-column osteotomy was not predictive of reoperation within 1 year, p =
      0.5476). There were no significant differences between groups with regard to the
      distribution of UIV, and UIV did not have a significant effect on reoperation
      rates. Patients needing reoperation within 1 year had worse ODI and SRS-22 scores
      measured at 1-year follow-up than patients not requiring operation. CONCLUSIONS:
      Analysis of data from a large multicenter adult spinal deformity database shows
      an overall 17% reoperation rate, with a 19% reoperation rate for patients treated
      with 3-column osteotomy and a 16% reoperation rate for patients not treated with
      3-column osteotomy. The most common indications for reoperation included
      instrumentation complications and radiographic failure. Reoperation significantly
      affected HRQOL outcomes at 1-year follow-up. The need for reoperation may be
      minimized by carefully considering spinal alignment, termination of fixation, and
      type of surgical procedure (presence of osteotomy). Precautions should be taken
      to avoid malposition or instrumentation (rod) failure.

PMID- 23971764
TI  - Intramedullary spinal capillary hemangiomas: clinical features and surgical
      outcomes: clinical article.
AB  - OBJECT: Intramedullary capillary hemangiomas are exceedingly rare lesions in the
      spinal cord, and have been previously reported in the literature as case reports.
      The authors review their experience in 5 surgically treated patients with
      intramedullary capillary hemangiomas and discuss the clinical features,
      radiological findings, and surgical outcomes. METHODS: Clinical and imaging data
      of 5 patients with intramedullary spinal capillary hemangiomas treated at a
      single institution were retrospectively analyzed. RESULTS: There were 4 men and 1
      woman, and their ages ranged from 18 to 63 years (mean 47.2 years). The thoracic
      cord was affected in 4 patients, and the cervicothoracic cord in 1 patient. Four
      patients underwent a gross-total resection. One patient initially underwent a
      subtotal removal and then underwent a second surgery due to enlargement of the
      residual lesion. Long-term neurological function was improved in all patients and
      MRI showed no tumor recurrence. CONCLUSIONS: Capillary hemangiomas should be
      considered in the differential diagnosis of intramedullary spinal vascular
      lesions. Complete resection is the treatment of choice for these lesions. When
      total resection cannot be achieved, subtotal or even partial removal of the tumor
      is advised and repeat removal of the lesion is indicated when residual tumor
      regrowth is associated with neurological deterioration.

PMID- 23971765
TI  - Radiographic and clinical outcome after 1- and 2-level transsacral axial
      interbody fusion: clinical article.
AB  - OBJECT: The paracoccygeal approach allows for instrumentation of L5/S1 and L4/5
      by using a transsacral rod (AxiaLIF; TransS1, Inc.). The authors analyzed
      clinical and radiographic outcomes of 1- or 2-level AxiaLIF procedures with focus
      on durability of the construct. METHODS: This was a retrospective study of 38
      consecutive patients who underwent either 1-level (32 patients) or 2-level (6
      patients) AxiaLIF procedures at the authors' institution. The Oswestry Disability
      Index (minimum clinically important difference [MCID] >= 12) and visual analog
      scale ([VAS]; MCID >= 3) scores were collected. Disc height and Cobb angles were
      measured on pre- and postoperative radiographs. Bony fusion was determined on CT
      scans or flexion/extension radiographs. RESULTS: Implantation of a transsacral
      rod allowed for intraoperative distraction of the L5/S1 intervertebral space and
      resulted in increased segmental lordosis postoperatively. At a mean follow-up
      time of 26.2 +/- 2.4 months, however, graft subsidence (1.9 mm) abolished partial
      correction of segmental lordosis. Moreover, subsidence of the construct reduced
      L5/S1 lordosis in patients with 1-level AxiaLIF by 3.2 degrees  and L4-S1
      lordosis in patients with 2-level procedures by 10.1 degrees  compared with
      preoperative values (p < 0.01). Loss of segmental lordosis predicted failure to
      improve VAS scores for back pain in the patient cohort (p < 0.05). Overall,
      surgical intervention led to modest symptomatic improvement; only 26.3% of
      patients achieved an MCID of the Oswestry Disability Index and 50% of patients an
      MCID of the VAS score for back pain. At last follow-up, 71.9% of L5/S1 levels
      demonstrated bony fusion (1-level AxiaLIF 80.8%, 2-level AxiaLIF 33.3%; p <
      0.05), whereas none of the L4/5 levels in 2-level AxiaLIF fused. Five constructs
      developed pseudarthrosis and required surgical revision. CONCLUSIONS: The AxiaLIF
      procedure constitutes a minimally invasive technique for L5/S1 instrumentation,
      with low perioperative morbidity. However, the axial rod provides inadequate long
      term anterior column support, which leads to subsidence and loss of segmental
      lordosis. Modification of the transsacral technique to allow for placement of a
      solid interposition graft may counteract subsidence of the construct.

PMID- 23971766
TI  - No association between VAPB mutations and familial or sporadic ALS in Sweden,
      Portugal and Iceland.
AB  - Linkage analysis in Brazilian families with amyotrophic lateral sclerosis (ALS)
      revealed that a missense mutation p.Pro56Ser in a conserved gene VAMP-associated
      protein type B and C (VAPB) cosegregates with disease. Blood samples were studied
      from 973 Swedish, 126 Portuguese and 19 Icelandic ALS patients, and from 644
      control subjects. We identified five VAPB mutations, two of which are novel, in
      14 Swedish ALS patients and in nine control individuals from Sweden and Portugal.
      The 14 patients with VAPB mutations all carried a diagnosis of sporadic ALS.
      Mutations were also found in healthy adult relatives. The p.Asp130Glu VAPB
      mutation was also found in two patients from an Icelandic ALS family, but the
      mutation did not cosegregate with disease. All patients were instead found to be
      heterozygous for a p.Gly93Ser SOD1 mutation. There were no clinical differences
      between them, suggesting that the p.Asp130Glu VAPB mutation is unrelated to the
      disease process. In conclusion, the VAPB mutations were as frequent in control
      individuals as in patients. This observation, in combination with the finding of
      several healthy relatives carrying the VAPB mutations and no ancestors with ALS
      disease, suggests that it is unlikely that these VAPB mutations are pathogenic.

PMID- 23971767
TI  - Daily physical activity in ankylosing spondylitis: validity and reliability of
      the IPAQ and SQUASH and the relation with clinical assessments.
AB  - INTRODUCTION: The aim of this study was to investigate the construct validity and
      test-retest reliability of the International Physical Activity Questionnaire
      (IPAQ; long form) and the Short QUestionnaire to Assess Health-enhancing physical
      activity (SQUASH) and to investigate the relation between daily physical activity
      and clinical assessments in patients with ankylosing spondylitis (AS). METHODS:
      For validity, the self-report questionnaires IPAQ and SQUASH were compared with
      daily physical activity assessed with the ActiGraph accelerometer during 7
      consecutive days in 63 AS outpatients. For reliability, the IPAQ and SQUASH were
      administered twice approximately 1 week apart in 52 AS outpatients. In all 115
      patients, clinical assessments were performed at the outpatient clinic. RESULTS:
      IPAQ and SQUASH total scores correlated significantly with accelerometer outcome:
      rho = 0.38 and r = 0.35, respectively. Intraclass correlation coefficients
      between first and second assessments of the IPAQ and SQUASH were 0.83 and 0.89,
      respectively. Bland-Altman analyses showed no systemic bias, but in particular
      for the IPAQ the 95% limits of agreement were wide. Daily physical activity
      assessed by accelerometer, IPAQ, and SQUASH correlated significantly with disease
      activity, physical activity, and quality of life. A relation with spinal mobility
      was found only for the accelerometer and SQUASH. The direction of these
      correlations indicates that higher daily physical activity is related to lower
      disease activity and better physical function, spinal mobility and quality of
      life. CONCLUSIONS: Both physical activity questionnaires showed modest construct
      validity. The SQUASH showed good test-retest reliability, superior to the IPAQ.
      These results indicate that the SQUASH is more suitable than the IPAQ to assess
      daily physical activity in AS population studies. However, it is desirable to add
      questions on AS-specific physical activity. Further studies are needed to
      investigate the causality of the relation between daily physical activity and
      clinical assessments.

PMID- 23971769
TI  - Clinical and pathologic prognostic factors that are influential in the survival
      and prognosis of lung adenocarcinomas and invasive predominant subtypes.
AB  - Therapeutic approaches to lung adenocarcinomas differ because of their
      heterogeneous morphologies, prognoses, and clinical features. For this reason,
      new histopathologic classifications for lung adenocarcinomas were done by the
      International Association for the Study of Lung Cancer/American Thoracic
      Society/European Respiratory Society to form subtypes with homogeneous prognoses.
      There are limited clinical data in the literature on the prognosis of the
      subgroups formed according to the new classification. A total of 86 patients with
      adenocarcinoma who had undergone pathologic stages I and II curative resection
      and mediastinal lymph node dissection were retrospectively analyzed according to
      the seventh TNM staging system revised by the Union for International Cancer
      Control/American Joint Committee on Cancer. Histologic subtyping was reassessed
      according to the dominant histopathologic morphology. When survival rates of lung
      adenocarcinomas were compared according to their localizations, it was observed
      that adenocarcinomas localized to the right hemithorax had a longer survival than
      the ones with left hemithorax localization (P = 0.026). When necrosis was taken
      into account, it was seen that necrosis rate was higher in solid predominant type
      compared with other types, whereas it was lower in acinary type (P = 0.046). When
      peritumoral lymphovascular invasion data were assessed, it was observed that
      disease-free survival was influenced in a negative fashion (P = 0.018). New
      histopathologic classification of adenocarcinomas has been a step forward to
      attaining homogeneous groups, but when the biologic heterogeneity of the
      adenocarcinomas is taken into account, the authors believe that considering the
      peritumoral lymphatic vascular invasion, left hemithorax localization, and
      tumoral necrosis entities in the upcoming TNM classification will contribute to
      evaluating the prognosis.

PMID- 23971770
TI  - Sex differences between cT4b and pT4b rectal cancers.
AB  - We retrospectively evaluated rectal cancer surgery cases in which resection had
      been performed for invasion of other organs in terms of pathologic findings from
      the viewpoint of sex differences. We enrolled 61 consecutive patients with rectal
      cancer who had undergone curative surgery with resection of invaded adjacent
      organs. We investigated invasion of adjacent organs in terms of pathologic
      findings according to sex differences. Among males, 4 cases (13.8%) had received
      combined radical resections of more than 2 organs, while the number of such
      female cases was 15 (46.9%). The difference between males and females was
      statistically significant (P = 0.006). Among male cases, histopathologic invasion
      was present in 4 (13.8%), while 9 female cases (28.1%) showed this feature.
      Nevertheless, there was not a statistically significant difference between males
      and females (P = 0.08); the rate in females was roughly twice that in males. No
      significant difference was recognized in the overall survival rates between males
      and females, but more females than males experienced local recurrence. In cases
      with rectal cancer invading neighboring organs, the effect of the invasion must
      be carefully determined, and the most appropriate operative approach selected
      accordingly.

PMID- 23971771
TI  - Rational manipulation of the standard laparoscopic instruments for single
      incision laparoscopic right colectomy.
AB  - This report clarifies the rational manipulation of standard laparoscopic
      instruments for single-incision laparoscopic right colectomy (SILRC) using the
      SILS Port. We classified the manipulations required into 4 techniques. Vertical
      manipulation was required for medial-to-lateral retroperitoneal dissection.
      Frontal manipulation was needed for extension and establishment of a
      retroperitoneal plane. External crossing manipulation was used for dissection or
      ligation of the ileocolic or right colic vessels. Internal crossing manipulation
      was required for mobilization from the cecum to ascending colon. We performed
      SILRC for a series of 30 consecutive patients. One additional port was needed in
      5 of the patients (16.7%) because of severe adhesion between the ileum and
      abdominal wall. No intraoperative complications were encountered. Four rational
      manipulations of the standard laparoscopic instruments are required for SILRC
      using the SILS Port. However, more experience and comparative trials are needed
      to determine the exact role of SILRC.

PMID- 23971772
TI  - Impact of less invasive treatments including sclerotherapy with a new agent and
      hemorrhoidopexy for prolapsing internal hemorrhoids.
AB  - Conventional hemorrhoidectomy is applied for the treatment of prolapsing internal
      hemorrhoids. Recently, less-invasive treatments such as sclerotherapy using
      aluminum potassium sulphate/tannic acid (ALTA) and a procedure for prolapse and
      hemorrhoids (PPH) have been introduced. We compared the results of sclerotherapy
      with ALTA and an improved type of PPH03 with those of hemorrhoidectomy. Between
      January 2006 and March 2009, we performed hemorrhoidectomy in 464 patients, ALTA
      in 940 patients, and PPH in 148 patients with second- and third-degree internal
      hemorrhoids according to the Goligher's classification. The volume of ALTA
      injected into a hemorrhoid was 7.3 +/- 2.2 (mean +/- SD) mL. The duration of the
      operation was significantly shorter in ALTA (13 +/- 2 minutes) than in
      hemorrhoidectomy (43 +/- 5 minutes) or PPH (32 +/- 12 minutes). Postoperative
      pain, requiring intravenous pain medications, occurred in 65 cases (14%) in
      hemorrhoidectomy, in 16 cases (1.7%) in ALTA, and in 1 case (0.7%) in PPH. The
      disappearance rates of prolapse were 100% in hemorrhoidectomy, 96% in ALTA, and
      98.6% in PPH. ALTA can be performed on an outpatient basis without any severe
      pain or complication, and PPH is a useful alternative treatment with less pain.
      Less-invasive treatments are beneficial when performed with care to avoid
      complications.

PMID- 23971773
TI  - Abdominal schwannomas: case report with literature review.
AB  - Schwannomas are rare tumors that arise from Schwann cells in neural sheaths. They
      are commonly found in the central nervous system, spinal cord, or peripheral
      nerves of the body. Occasionally, they occur in the gastrointestinal tract, with
      the stomach being the most common site. However, colorectal and retroperitoneal
      schwannomas are very rare. Preoperative diagnosis is often difficult and
      definitive treatment entails surgical excision. We herein present 3 cases of
      intraabdominal schwannomas.

PMID- 23971774
TI  - Laparoscopic resection of a retroperitoneal liposarcoma: a case report and review
      of the literature.
AB  - Here, we describe a case of a retroperitoneal liposarcoma successfully managed by
      laparoscopic surgery. A 72-year-old man underwent abnormal hypertension screening
      using computed tomography (CT), which revealed a low-density mass measuring 7 cm
      in diameter in the retroperitoneal space. We diagnosed the mass as a liposarcoma
      before the operation. The mass was resected laparoscopically. No perioperative
      complications were encountered, and the patient was discharged on the fourth
      postoperative day. The pathologic diagnosis was well-differentiated liposarcoma,
      indicating complete surgical resection. Thus, we conclude that a laparoscopic
      approach for the patients with retroperitoneal tumors, including liposarcomas, is
      safe, feasible, and minimally invasive, even if there is a possibility of the
      tumor being malignant.

PMID- 23971775
TI  - Interventional therapy for the treatment of severe hemobilia after percutaneous
      transhepatic cholangial drainage: a case series.
AB  - From May 2003 to May 2010, a total of 9 patients with severe hemobilia after
      percutaneous transhepatic cholangial drainage (PTCD) were diagnosed using
      superselective angiography and cholangiography, and then were treated with
      interventional procedures. Two patients with hepatic arterio-biliary fistula
      underwent proximal and distal arterial embolization of the responsible vessel.
      Six patients with pseudoaneurysm had pseudoaneurysm occlusion with proximal and
      distal embolization. Another patient with biliary-portal vein fistula received a
      biliary fully covered stent placement. The effects in these patients were
      evaluated using superselective angiography immediately after the intervention and
      at 3- and 6-month follow-up. In all patients, hemobilia was stopped right after
      the treatment and no sign of recurrence was noted at 3- and 6-month follow-up
      after the interventional therapy. Our findings demonstrate that interventional
      therapy is a simple, minimally invasive, and safe approach for treating severe
      hemobilia in patients receiving PTCD.

PMID- 23971776
TI  - Bilateral lower limb edema caused by compression of the retrohepatic inferior
      vena cava by a giant hepatic hemangioma.
AB  - Hemangiomas are the most common benign primary tumors of the liver and their
      prevalence ranges from 0.4% to 20%. Approximately 85% of hemangiomas are
      clinically asymptomatic and are incidentally detected in imaging studies
      performed for other causes. In a very small minority of patients, nausea,
      vomiting, abdominal pain, distension, palpable mass, obstructive jaundice,
      bleeding, and signs and symptoms of Budd-Chiari syndrome may develop due to
      compression of bile duct, hepatic vein, portal vein, and adjacent organs.
      Occasionally, external compression of inferior vena cava may lead to edema and/or
      indirect symptoms such as deep vein thrombosis of the lower limbs. In this
      report, we present a case of giant hepatic hemangioma that completely filled the
      right lobe of the liver. The patient presented with bilateral lower limb edema
      and pain. A computed tomography scan detected a 9 * 11 * 12 cm mass indicative of
      a hemangioma in the right lobe of the liver that compressed the inferior vena
      cava. The patient refused treatment initially but returned 6 months later
      presenting with the same symptoms. At that time, the mass had increased in size
      and a hepatectomy was performed, preserving the middle hepatic vein. By
      postoperative month 13, the swelling in the lower extremities had decreased
      significantly and the inferior vena cava appeared normal.

PMID- 23971777
TI  - Significance of tumor length as prognostic factor for esophageal cancer.
AB  - Our study indicated the relationship between tumor length and clinicopathologic
      characteristics as well as long-term survival in esophageal cancer. A total of
      116 patients who underwent curative surgery for thoracic esophageal cancer with
      standard lymphadenectomy in 2 fields between 2000 and 2010 were included in the
      study. The medical records of these patients were retrospectively reviewed. The
      patients with tumor length 3 cm had a highly significant difference in the
      involvement of adventitia and lymph node stations. The patients with tumor length
      3 cm had significantly lower rates of involvement of the adventitia and lymph
      node stations. Tumor length could have a significant impact on both the overall
      survival and disease-free survival of patients with resected esophageal
      carcinomas and may provide additional prognostic value to the current tumor,
      node, and metastasis staging system before patients receive any cancer-specific
      treatment.

PMID- 23971778
TI  - Long-term recurrence-free survival after metachronous surgery of the stomach and
      liver for gastric adenocarcinoma and multiple, synchronous liver metastases: a
      case report and review of literature.
AB  - This report describes a 58-year-old woman with gastric adenocarcinoma and liver
      metastases, who survives for more than 18 years after diagnosis. At diagnosis and
      first surgery, a moderately differentiated gastric adenocarcinoma with subserosal
      invasion was detected, along with 2 regional lymph node metastases and 2 liver
      metastases. She underwent gastrectomy and regional lymph node dissection but did
      not undergo liver operation then. After gastrectomy, she received adjuvant
      chemotherapy for 1 month but discontinued it due to severe diarrhea. Another
      metastasis in another area of the liver was detected, for which she underwent
      excision of the right lobe of the liver (subsegments 5, 6, and 7) about 30 months
      later. No signs of recurrence have been detected for 18 years (as of March 2012).
      This patient represents a rare case of long-term survival of gastric
      adenocarcinoma without recurrence after surgical treatment, despite multiple,
      synchronous, liver and regional lymph node metastases.

PMID- 23971779
TI  - Comparison of the invasiveness between reduced-port laparoscopy-assisted distal
      gastrectomy and conventional laparoscopy-assisted distal gastrectomy.
AB  - It is unknown whether reduced-port gastrectomy has a less invasive nature than
      conventional laparoscopy-assisted distal gastrectomy (C-LADG). So we compared 30
      cases of dual-port laparoscopy-assisted distal gastrectomy (DP-LADG; using an
      umbilical port plus a right flank 5-mm port) as a reduced-port gastrectomy with
      30 cases of C-LADG alternately performed by a single surgeon. No significant
      differences were observed in blood loss, intraoperative complications, the number
      of dissected lymph nodes, postoperative complications, the day of first
      defecation, analgesic agents required, changes in body temperature, heart rate,
      white blood cell count, serum albumin level, or lymphocyte count between the 2
      groups. The amounts of oral intake in the DP-LADG group were significantly higher
      on postoperative days 9 and 10. We concluded that the amount of oral intake in
      the DP-LADG group was superior to that in the C-LADG group; however, no other
      evidence of DP-LADG being less invasive than C-LADG was obtained.

PMID- 23971780
TI  - A case of intestinal obstruction caused by prominent kyphosis resulting in
      compression of the intestine by the costal arch.
AB  - An 85-year-old woman with no history of abdominal surgery complained of abdominal
      pain and vomiting and was referred to us with a diagnosis of intestinal
      obstruction a few days later. Upon admission to our facility, she presented with
      marked abdominal swelling and prominent kyphosis. Because of the kyphosis, most
      of the dilated bowel was compressing her thoracic cavity. No obvious
      strangulation or free air was observed via abdominal computed tomography imaging.
      We attempted decompression using a nasogastric tube, but the symptoms persisted.
      Surgery was performed 2 days after admission. The origin of the obstruction was a
      compression of the ileocecal region by the costal arch. The bowel was discolored,
      and thus surgically excised. There were no major postsurgical complications other
      than a mild wound infection. Until now, there have been no reports of advanced
      kyphosis inducing ileus, but there are concerns of an increase in similar cases
      as society continues to age.

PMID- 23971781
TI  - Comparison of three different minimally invasive procedures of distal gastrectomy
      for Nonoverweight patients with T1N0-1 gastric cancer.
AB  - Laparoscopic-assisted distal gastrectomy has recently come to be a standard
      procedure for the treatment of early gastric cancer (1 - 5) in select patients.
      The minimal invasiveness associated with laparoscopic procedures for the
      resection of gastrointestinal cancer has been repeatedly explained in part by the
      short incision that is required. (6 - 11) We used two different approaches to
      perform distal gastrectomies for the resection of gastric cancer as minimally
      invasive alternatives to a standard laparoscopic approach prior to our surgical
      team's complete mastery of the skills required for laparoscopic oncological
      surgery for gastric cancer. (9 , 12) If the minimal invasiveness associated with
      laparoscopic-assisted gastrectomy can be explained by the small incision, a
      gastrectomy via a small incision without the use of a pneumoperitoneum may
      provide a similar outcome in patients. However, to our knowledge, such a
      comparison has not been previously made. We compared the minimal invasiveness of
      three different approaches (minilaparotomy, minilaparotomy approach with
      laparoscopic assistance, and standard laparoscopic-assisted approach) to
      performing a distal gastrectomy for T1N0-1 gastric cancer in nonoverweight
      patients (body mass index, <= 25 kg/m(2)) performed within a limited study
      period.

PMID- 23971782
TI  - Laparoscopy-assisted distal gastrectomy for an early gastric cancer patient with
      situs inversus totalis.
AB  - Situs inversus totalis (SIT) is a congenital condition in which there is complete
      right to left reversal of the thoracic and abdominal organs. This report
      describes laparoscopy-assisted distal gastrectomy (LADG) for an early gastric
      cancer patient with SIT. The preoperative diagnosis was c-stage IA (cT1a cN0 cH0
      cP0 cM0). LADG with D1+ dissection and Billroth-I reconstruction was successfully
      performed by standing at the opposite position. The operating time was 234
      minutes and blood loss was 5 mL. Although a mechanical obstruction occurred after
      surgery, the patient recovered after re-operation with Roux-en-Y bypass.

PMID- 23971785
TI  - An overview of what we are about.

PMID- 23971784
TI  - Splenic artery transposition graft usage for the supply of the right hepatic
      artery: a case report.
AB  - Hepatic artery aneurysms are responsible for 12% to 20% of all visceral arterial
      aneurysms. Because most patients are asymptomatic, this disease is generally
      diagnosed incidentally during radiologic examination. Aneurysm rupture develops
      in 14% to 80% of cases, depending on the aneurysmatic segment's diameter and
      location, as well as other etiologic factors. Mortality rates associated with
      rupture range between 20% and 70%. Thus, early diagnosis and timely initiation of
      medical interventions are critical to improve survival rates. Here, we present a
      male patient, age 69 years, with a hepatic artery aneurysm that was detected
      incidentally. The 3-cm aneurysm was detected on contrast-enhanced computed
      tomography and extended from the common hepatic artery to the hepatic
      trifurcation. A laparotomy was performed using a right subcostal incision. After
      dissection of the hepatoduodenal ligament, the common, right, and left hepatic
      arteries, as well as the gastroduodenal artery, were suspended separately. Then,
      the aneurysmatic hepatic artery segment was resected, and the gastroduodenal
      artery stump was ligated. An end-to-end anastomosis was formed between the left
      and common hepatic arteries, followed by an end-to-end anastomosis formed between
      the right hepatic artery and splenic artery using a splenic artery transposition
      graft. Postoperative follow-up examinations showed that both hepatic arterial
      circulations were good, and no splenic infraction had developed.

PMID- 23971783
TI  - Oncologic outcome with use of sodium hyaluronate-carboxymethylcellulose barrier
      in gastric cancer.
AB  - Hyaluronan is a component of an anti-adhesive barrier and has been implicated in
      tumor growth and metastasis. We aimed to determine whether this anti-adhesive
      barrier was associated with rates of postoperative complications and duration of
      survival in patients with gastric cancer. We identified 415 consecutive patients
      with gastric cancer who underwent gastrectomy. Information about patients'
      demographics, medical history, surgical procedures, postoperative complications,
      disease stage, histology, and survival was collected from medical records. One
      hundred and ninety-six patients received intraoperative placement of an anti
      adhesive barrier composed of hyaluronan-carboxymethylcellulose (HA-CMC) (HA-CMC
      group), and 219 did not (control group). The incidence of postoperative
      complications was significantly increased in the control group (22.8%) compared
      with the HA-CMC group (13.3%). However, there was no significant difference in
      overall survival between the HA-CMC and control groups. Our study suggests that
      the anti-adhesive barrier does not affect oncologic outcome, nor does it increase
      postoperative complications in patients undergoing surgery for gastric cancer.

PMID- 23971786
TI  - Sequential changes of serum antithyroglobulin antibody levels are a good
      predictor of disease activity in thyroglobulin-negative patients with papillary
      thyroid carcinoma.
AB  - OBJECTIVE: To investigate whether elevated and sequential changes in serum
      antithyroglobulin antibody (TgAb) levels are indicators of recurrence or
      persistence of papillary thyroid cancer (PTC) in patients with undetectable
      thyroglobulin. METHODS: In 56 patients followed for more than 7 years, we
      recorded all serum TgAb levels (except the ones determined within one year after
      (131)I therapy or diagnostic scans) and evaluated their disease status. All
      patients had undergone total thyroidectomy and remnant ablation by (131)I, and
      they were positive for TgAb and had undetectable thyroglobulin during follow-up.
      The sequential changes of TgAb were defined as persistently high, increasing,
      persistently medium, decreasing, and decreasing to negative. Recurrence or
      persistence of PTC was defined as active disease as assessed by (131)I scanning,
      (18)F-fluorodeoxyglucose positron emission tomography, ultrasonography, computed
      tomography, or surgical examination. RESULTS: Of the 56 patients enrolled, 10
      patients had persistent PTC and 12 patients had recurrent PTC at more than 1 year
      after total thyroidectomy and (131)I therapy. TgAb was persistently high in 4
      patients (3 with active PTC), increasing in 6 patients (4 with active PTC),
      persistently medium in 16 patients (12 with active PTC), decreasing in 5 patients
      (none with active PTC), and decreased to negative in 25 patients (3 with active
      PTC). According to the trend, the patients with persistently high TgAb,
      increasing TgAb, and persistently medium TgAb had active disease more often
      (p<0.001). In the multivariable regression analyses, the trend of TgAb change was
      a strong predictor of PTC activity (p<0.001, R(2)=-0.501). The most common
      diagnostic procedures performed for active disease were neck ultrasonography (21
      patients) followed by (18)F-fluorodeoxyglucose positron emission tomography (11
      patients). The patients with autoimmune thyroid disease had better prognoses than
      did the patients without autoimmune thyroid disease (18% active PTC vs. 53%
      active PTC, p=0.02). CONCLUSION: The presence of TgAb is indicative of an active
      tumor. Sequential TgAb change is a good predictor of disease prognosis and is
      helpful for clinical decision making.

PMID- 23971787
TI  - A highly electron-deficient analogue of aniline, soluble oligomers, and their
      redox properties.
AB  - The synthesis and electrochemical oxidative coupling of a highly electron
      deficient analogue of aniline results in the formation of soluble electron
      deficient oligomers. Oligomers undergo related oxidation and reduction processes
      that are separated by a wide potential range. The mechanism behind this behavior
      is examined by cyclic voltammetry, optical absorption spectroscopy, (1)H NMR
      spectroscopy, and density functional theory calculations. Mesomeric isomerization
      of the oxidized oligomers leads to a very stable oxidized state that requires a
      large (2.8 V) overpotential to return to the neutral form. 

PMID- 23971788
TI  - Circularity and self-cleavage as a strategy for the emergence of a chromosome in
      the RNA-based protocell.
AB  - BACKGROUND: It is now popularly accepted that an "RNA world" existed in early
      evolution. During division of RNA-based protocells, random distribution of
      individual genes (simultaneously as ribozymes) between offspring might have
      resulted in gene loss, especially when the number of gene types increased.
      Therefore, the emergence of a chromosome carrying linked genes was critical for
      the prosperity of the RNA world. However, there were quite a few immediate
      difficulties for this event to occur. For example, a chromosome would be much
      longer than individual genes, and thus more likely to degrade and less likely to
      replicate completely; the copying of the chromosome might start at middle sites
      and be only partial; and, without a complex transcription mechanism, the
      synthesis of distinct ribozymes would become problematic. RESULTS: Inspired by
      features of viroids, which have been suggested as "living fossils" of the RNA
      world, we supposed that these difficulties could have been overcome if the
      chromosome adopted a circular form and small, self-cleaving ribozymes (e.g. the
      hammer head ribozymes) resided at the sites between genes. Computer simulation
      using a Monte-Carlo method was conducted to investigate this hypothesis. The
      simulation shows that an RNA chromosome can spread (increase in quantity and be
      sustained) in the system if it is a circular one and its linear "transcripts" are
      readily broken at the sites between genes; the chromosome works as genetic
      material and ribozymes "coded" by it serve as functional molecules; and both
      circularity and self-cleavage are important for the spread of the chromosome.
      CONCLUSIONS: In the RNA world, circularity and self-cleavage may have been
      adopted as a strategy to overcome the immediate difficulties for the emergence of
      a chromosome (with linked genes). The strategy suggested here is very simple and
      likely to have been used in this early stage of evolution. By demonstrating the
      possibility of the emergence of an RNA chromosome, this study opens on the
      prospect of a prosperous RNA world, populated by RNA-based protocells with a
      number of genes, showing complicated functions.

PMID- 23971789
TI  - Early use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in type 2
      diabetes.
AB  - OBJECTIVE: To evaluate the efficacy and safety of the available glucagon-like
      peptide-1 receptor agonists (GLP-1 RAs) exenatide and liraglutide (marketed as
      Byetta * and Victoza ? , respectively) in first- or second-line pharmacotherapy
      for type 2 diabetes (T2D), described here as 'early use'. RESEARCH DESIGN AND
      METHODS: MEDLINE, EMBASE and Google Scholar databases were queried for clinical
      trial reports using the terms incretin, GLP-1, exenatide and liraglutide.
      Relevant articles were those that employed these agents in treatment-naive
      patients with T2D and in patients who had failed on metformin monotherapy.
      Additional targeted searches were conducted on diabetes treatment guidelines and
      on the range of physiological responses to GLP-1 RAs. Most evidence is level I
      and II. RESULTS: Effective therapy for T2D should be implemented early in the
      course of this progressive disease. The recently revised 2013 Canadian Diabetes
      Association (CDA) guidelines now identify the GLP-1 RAs among various injected
      and oral agents recommended for the management of T2D. The rationale for early
      use of GLP-1 RAs in T2D management is manifold: these agents offer effective
      management of hyperglycemia in early-stage T2D, minimal risk of hypoglycemia,
      weight loss, improvement in multiple non-glycemic cardiovascular risk factors,
      and potential enhancement of patient adherence to antihyperglycemic treatment.
      Available data from clinical trials support second-line use of GLP-1 RAs among
      patients who fail on metformin, as well as first-line use of these agents in a
      subset of T2D patients. CONCLUSIONS: The ability to achieve glycemic targets
      using GLP-1 RAs while simultaneously avoiding hypoglycemia and weight gain could
      provide substantial reassurance to physicians and patients who might otherwise
      resist the transition to injected therapies. Exenatide and liraglutide represent
      appropriate second-line choices for pharmacological treatment of T2D, as
      indicated in the 2013 CDA guidelines.

PMID- 23971790
TI  - Effects of Payena dasyphylla (Miq.) on hyaluronidase enzyme activity and
      metalloproteinases protein expressions in interleukin-1beta stimulated human
      chondrocytes cells.
AB  - BACKGROUND: Hyaluronidases have been found as the target enzymes in the
      development of osteoarthritis (OA) disease. While there is still no curative
      treatment for this disease, recent studies on the treatment of OA were focused on
      the effectiveness of natural products which are expected to improve the symptoms
      with minimal side effects. The aim of this study was to screen selected Malaysian
      plants on their anti-hyaluronidase activity as well as to evaluate the active
      plant and its derived fractions on its potential anti-arthritic and antioxidant
      activities. METHODS: A total of 20 methanolic crude extracts (bark and leaf) from
      ten different plants were screened using a colorimetric hyaluronidase enzymatic
      assay. The active plant extract (Payena dasyphylla) was then studied for its
      hyaluronidase inhibitory activity in the interleukin-1beta (IL-1beta) stimulated
      human chondrocytes cell line (NHAC-kn) using zymography method. The Payena
      dasyphylla methanolic bark extract was then fractionated into several fractions
      in where the ethyl acetate (EA) fraction was evaluated for its inhibitory effects
      on the HYAL1 and HYAL2 gene expressions using reverse transcription-polymerase
      chain reaction (RT-PCR) technique. While the MMP-3 and MMP-13 protein expressions
      were evaluated using western blot method. The phenolic and flavonoid contents of
      the three fractions as well as the antioxidant property of the EA fraction were
      also evaluated. RESULTS: Bark extract of Payena dasyphylla (100 MUg/ml) showed
      the highest inhibitory activity against bovine testicular hyaluronidase with
      91.63%. The plant extract also inhibited hyaluronidase expression in the cultured
      human chondrocyte cells in response to IL-1beta (100 ng/ml). Similarly, treatment
      with Payena dasyphylla ethyl acetate (EA) fraction (100 MUg/ml) inhibited the
      HYAL1 and HYAL2 mRNA gene expressions as well as MMP-3 and MMP-13 protein
      expression in a dose dependent manner. Payena dasyphylla EA fraction has
      demonstrated the highest amount of phenolic and flavonoid content with 168.62 +/-
      10.93 mg GAE/g and 95.96 +/- 2.96 mg RE/g respectively as compared to water and
      hexane fractions. In addition, the Payena dasyphylla EA fraction showed strong
      antioxidant activity with IC50 value of 11.64 +/- 1.69 MUg/mL. CONCLUSION: These
      findings have shown that Payena dasyphylla might contained potential phenolic
      compounds that inhibiting the key enzyme in osteoarthritis development, which is
      the hyaluronidase enzyme through interruption of HYAL1 and HYAL1 gene
      expressions. The degradation of cartilage could also be inhibited by the plant
      through suppression of MMP-3 and MMP-13 protein expressions. We also reported
      that the inhibitory effect of Payena dasyphylla on hyaluronidase activity and
      expression might be due to its anti-oxidant property.

PMID- 23971791
TI  - Predictive values of post-clopidogrel platelet reactivity assessed by different
      platelet function tests on ischemic events in East Asian patients treated with
      PCI.
AB  - Abstract An accumulating number of studies are revealing that platelet reactivity
      above specific cut-off scores leads to exponentially increased rates of post
      percutaneous coronary intervention (PCI) ischemic events. To evaluate the optimal
      predictive values for three different platelet function measurement assays of
      platelet reactivity on early clinical outcomes in Korean patients undergoing PCI,
      we enrolled 228 patients receiving clopidogrel prior to PCI. Platelet reactivity
      was measured by light transmittance aggregometry (LTA), VerifyNow P2Y12 assay,
      and multiple electrode platelet aggregometry (MEA). The primary endpoint was the
      30-day occurrence of ischemic events after PCI. MACE occurred in 36 patients
      (15.8%), including 35 patients (15.4%) with periprocedural MI and the death of
      one patient (0.4%). ADP-induced LTA and VerifyNow values (pre- and post-PCI) were
      significantly higher in patients with the subsequent occurrence of periprocedural
      MI, but the MEA assay data (PCI and post-PCI) displayed no significant
      differences (pre-PCI p=0.25 and post-PCI p=0.33). ROC curve analysis demonstrated
      HPR values for LTA (pre-PCI, >66% and post-PCI, >53 %, all p<0.001), VerifyNow
      (pre-PCI, >347 PRU and post-PCI >272 PRU, all p<0.001) and MEA (pre-PCI, >50 U
      and post-PCI >39 U, all p>0.05). The platelet reactivity measurements by LTA and
      the VerifyNow assay can discriminate the risk of 30-day ischemic events after
      PCI. The predictive cut-off values for adverse events are dependent on sampling
      time.

PMID- 23971792
TI  - Electrochemical versus spectrophotometric assessment of antioxidant activity of
      hop (Humulus lupulus L.) products and individual compounds.
AB  - Antioxidant (AO) activity of extracts of hop cones (Serbian domestic varieties)
      and commercial hop products (Saaz, Spalter, Spalter select, and Magnum pellets)
      was determined by parallel application of recently developed direct current (DC)
      polarographic and widely used DPPH assay. Correlations between 2,2-diphenyl-1
      picrylhydrazyl radical (DPPH) scavenging and total phenolics (TPC) determined by
      the Folin-Ciocalteu assay (FC) (0.99), and between H2O2 scavenging (HPS) and
      humulone content (H) determined by conductometric method (0.94), total resins
      (TR) (0.85), and hop storage index (HIS) (-0.90), were found statistically
      significant at p < 0.05 level while complete lack of HPS correlation with TPC and
      DPPH was observed. To obtain an insight into differences between results of AO
      assays applied, activity of individual compounds, prevalent hop phenolics, and
      bitter acids was determined. By far superior HPS activity of humulone was
      followed by catechin, quercetin, xanthohumol, lupulone, and rutin. In contrast,
      DPPH scavenging activity of phenolics (quercetin > catechin > rutin > xantohumol)
      was found substantially higher than activity of bitter acids. According to ferric
      reducing antioxidant power (FRAP) and scavenging of 2,2-azino-bis-3
      ethylbenzothiazoline-6-sulfonic acid (ABTS), higher AO activity was ascribed to
      phenolics, while almost neglecting humulone. Besides reliability, low cost, and
      an easy-to-handle procedure, an ability to recognize humulone as the major
      contributor of hop AO activity could allow DC polarographic assay to be applied
      in analysis of various hop-derived products. 

PMID- 23971793
TI  - Influence of surface potential on the adhesive force of radioactive gold
      surfaces.
AB  - Radioactive particles may acquire surface potential through self-charging, and
      thus can behave differently from natural aerosols in atmospheric systems with
      respect to aggregation, deposition, resuspension, and transport to areas
      surrounding a radioactive source. This work focuses on the adhesive force between
      radioactive particles and metallic surfaces, which relates to the deposition and
      resuspension of particles on surrounding surfaces. Scanning surface potential
      microscopy was employed to measure the surface potential of radioactive gold
      foil. Atomic force microscopy was used to investigate the adhesive force for gold
      that acquired surface charge either by irradiation or by application of an
      equivalent electrical bias. Overall, the adhesive force increases with increasing
      surface potential or relative humidity. However, a behavior that does not follow
      the general trend was observed for the irradiated gold at a high decay rate. A
      comparison between experimental measurements and calculated values revealed that
      the surface potential promotes adhesion. The contribution of the electrostatic
      force at high levels of relative humidity was lower than the one found using
      theoretical calculations due to the effects caused by enhanced adsorption rate of
      water molecules under a high surface charge density. The results of this study
      can be used to provide a better understanding of the behavior of radioactive
      particles in atmospheric systems. 

PMID- 23971794
TI  - A multidisciplinary approach to increasing preparedness against bioterrorism.

PMID- 23971795
TI  - Decontamination of high-risk animal and zoonotic pathogens.
AB  - Preparedness for the decontamination of affected environments, premises,
      facilities, and products is one prerequisite for an immediate response to an
      animal disease outbreak. Various information sources provide recommendations on
      how to proceed in an outbreak situation to eliminate biological contaminants and
      to stop the spread of the disease. In order to facilitate the identification of
      the right decontamination strategy, we present an overview of relevant references
      for a collection of pathogenic agents. The choice of pathogens is based on a
      survey of lists containing highly pathogenic agents and/or biological agents
      considered to be potential vehicles for deliberate contamination of food, feed,
      or farm animals. European legislation and guidelines from national and
      international institutions were screened to find decontamination protocols for
      each of the agents. Identified recommendations were evaluated with regard to
      their area of application, which could be facilities and equipment, wastes, food,
      and other animal products. The requirements of a disinfectant for large-scale
      incidents were gathered, and important characteristics (eg, inactivating
      spectrum, temperature range, toxicity to environment) of the main recommended
      disinfectants were summarized to assist in the choice of a suitable and efficient
      approach in a crisis situation induced by a specific high-risk animal or zoonotic
      pathogen. The literature search revealed numerous relevant recommendations but
      also legal gaps for certain diseases, such as Q fever or brucellosis, and legal
      difficulties for the use of recommended disinfectants. A lack of information
      about effective disinfectants was identified for some agents. 

PMID- 23971796
TI  - Control of the deliberate spread of foot-and-mouth disease virus.
AB  - Foot-and-mouth disease (FMD) is one of the most feared of transboundary animal
      diseases. Accidental or deliberate release of the causative agent can have both
      direct and indirect effects that result in massive economic losses and
      disruption. The direct effects of an FMD outbreak include immediate losses to
      agricultural production and disruption of local economies, while the indirect
      effects are mainly related to disease control measures such as restriction of
      market access at local and global levels and the high costs of disease control.
      To improve the capacity of the European Union (EU) to counter animal bioterrorism
      threats, AniBioThreat was launched with a special focus on threats to living
      animals, feed, and food of animal origin. As part of this project, several
      zoonotic or animal pathogenic agents are considered from different perspectives.
      FMD virus was selected as one agent to be scrutinized because it is highly
      contagious and an outbreak can have a severe economic impact. Ways to fight a
      deliberate outbreak can be demonstrated through the example of FMD. In this
      article, the virology and epidemiology of FMD virus are discussed with special
      attention to the related law enforcement aspects. 

PMID- 23971797
TI  - Detecting bioterrorism: how to detect the unexpected?

PMID- 23971798
TI  - Analysis of research publications that relate to bioterrorism and risk
      assessment.
AB  - Research relating to bioterrorism and its associated risks is interdisciplinary
      and is performed with a wide variety of objectives. Although published reports of
      this research have appeared only in the past decade, there has been a steady
      increase in their number and a continuous diversification of sources, content,
      and document types. In this analysis, we explored a large set of published
      reports, identified from accessible indices using simple search techniques, and
      tried to rationalize the patterns and connectivity of the research subjects
      rather than the detailed content. The analysis is based on a connectivity network
      representation built from author-assigned keywords. Network analysis reveals a
      strong relationship between research aimed at bioterrorism risks and research
      identified with public health. Additionally, the network identifies clusters of
      keywords centered on emergency preparedness and food safety issues. The network
      structure includes a large amount of meta-information that can be used for
      assessment and planning of research activity and for framing specific research
      interests. 

PMID- 23971799
TI  - A generic open-source software framework supporting scenario simulations in
      bioterrorist crises.
AB  - Since the 2001 anthrax attack in the United States, awareness of threats
      originating from bioterrorism has grown. This led internationally to increased
      research efforts to improve knowledge of and approaches to protecting human and
      animal populations against the threat from such attacks. A collaborative effort
      in this context is the extension of the open-source Spatiotemporal
      Epidemiological Modeler (STEM) simulation and modeling software for agro- or
      bioterrorist crisis scenarios. STEM, originally designed to enable community
      driven public health disease models and simulations, was extended with new
      features that enable integration of proprietary data as well as visualization of
      agent spread along supply and production chains. STEM now provides a fully
      developed open-source software infrastructure supporting critical modeling tasks
      such as ad hoc model generation, parameter estimation, simulation of scenario
      evolution, estimation of effects of mitigation or management measures, and
      documentation. This open-source software resource can be used free of charge.
      Additionally, STEM provides critical features like built-in worldwide data on
      administrative boundaries, transportation networks, or environmental conditions
      (eg, rainfall, temperature, elevation, vegetation). Users can easily combine
      their own confidential data with built-in public data to create customized models
      of desired resolution. STEM also supports collaborative and joint efforts in
      crisis situations by extended import and export functionalities. In this article
      we demonstrate specifically those new software features implemented to accomplish
      STEM application in agro- or bioterrorist crisis scenarios. 

PMID- 23971800
TI  - Metagenomic detection methods in biopreparedness outbreak scenarios.
AB  - In the field of diagnostic microbiology, rapid molecular methods are critically
      important for detecting pathogens. With rapid and accurate detection, preventive
      measures can be put in place early, thereby preventing loss of life and further
      spread of a disease. From a preparedness perspective, early detection and
      response are important in order to minimize the consequences. During the past 2
      decades, advances in next-generation sequencing (NGS) technology have changed the
      playing field of molecular methods. Today, it is within reach to completely
      sequence the total microbiological content of a clinical sample, creating a
      metagenome, in a single week of laboratory work. As new technologies emerge,
      their dissemination and capacity building must be facilitated, and criteria for
      use, as well as guidelines on how to report results, must be established. This
      article focuses on the use of metagenomics, from sample collection to data
      analysis and to some extent NGS, for the detection of pathogens, the integration
      of the technique in outbreak response systems, and the risk-based evaluation of
      sample processing in routine diagnostics labs. The article covers recent advances
      in the field, current debate, gaps in research, and future directions. Examples
      of metagenomic detection, as well as possible applications of the methods, are
      described in various biopreparedness outbreak scenarios. 

PMID- 23971801
TI  - Evaluation of direct 16S rDNA sequencing as a metagenomics-based approach to
      screening bacteria in bottled water.
AB  - Deliberate or accidental contamination of food, feed, and water supplies poses a
      threat to human health worldwide. A rapid and sensitive detection technique that
      could replace the current labor-intensive and time-consuming culture-based
      methods is highly desirable. In addition to species-specific assays, such as PCR,
      there is a need for generic methods to screen for unknown pathogenic
      microorganisms in samples. This work presents a metagenomics-based direct
      sequencing approach for detecting unknown microorganisms, using Bacillus cereus
      (as a model organism for B. anthracis) in bottled water as an example. Total DNA
      extraction and 16S rDNA gene sequencing were used in combination with principle
      component analysis and multicurve resolution to study detection level and
      possibility for identification. Results showed a detection level of 10(5) to
      10(6) CFU/L. Using this method, it was possible to separate 2 B. cereus strains
      by the principal component plot, despite the close sequence resemblance. A linear
      correlation between the artificial contamination level and the relative amount of
      the Bacillus artificial contaminant in the metagenome was observed, and a
      relative amount value above 0.5 confirmed the presence of Bacillus. The analysis
      also revealed that background flora in the bottled water varied between the
      different water types that were included in the study. This method has the
      potential to be adapted to other biological matrices and bacterial pathogens for
      fast screening of unknown bacterial threats in outbreak situations. 

PMID- 23971802
TI  - Genetic diversity of Bacillus anthracis in Europe: genotyping methods in forensic
      and epidemiologic investigations.
AB  - Bacillus anthracis, the etiological agent of anthrax, a zoonosis relatively
      common throughout the world, can be used as an agent of bioterrorism. In
      naturally occurring outbreaks and in criminal release of this pathogen, a fast
      and accurate diagnosis is crucial to an effective response. Microbiological
      forensics and epidemiologic investigations increasingly rely on molecular
      markers, such as polymorphisms in DNA sequence, to obtain reliable information
      regarding the identification or source of a suspicious strain. Over the past
      decade, significant research efforts have been undertaken to develop genotyping
      methods with increased power to differentiate B. anthracis strains. A growing
      number of DNA signatures have been identified and used to survey B. anthracis
      diversity in nature, leading to rapid advances in our understanding of the global
      population of this pathogen. This article provides an overview of the different
      phylogenetic subgroups distributed across the world, with a particular focus on
      Europe. Updated information on the anthrax situation in Europe is reported. A
      brief description of some of the work in progress in the work package 5.1 of the
      AniBioThreat project is also presented, including (1) the development of a robust
      typing tool based on a suspension array technology and multiplexed single
      nucleotide polymorphisms scoring and (2) the typing of a collection of DNA from
      European isolates exchanged between the partners of the project. The know-how
      acquired will contribute to improving the EU's ability to react rapidly when the
      identity and real origin of a strain need to be established. 

PMID- 23971803
TI  - Historical perspective on agroterrorism: lessons learned from 1945 to 2012.
AB  - This article presents a historical perspective on agroterrorism cases from 1945
      until 2012. The threat groups and perpetrators associated with bio- and
      agroterrorism are clustered into several groups: apocalyptic sects, lone wolves,
      political groups, and religious groups. We used open-source information, and 4
      biological agroterrorism cases are described: (1) in 1952, Mau Mau poisoned
      cattle in Kenya by using a plant toxin from the African milk bush plant; (2) in
      1985, the USDA claimed that Mexican contract workers were involved in
      deliberately spreading screwworm (Cochliomyia hominivorax) among livestock; (3)
      in 2000, Palestinian media reported that Israeli settlers released sewer water
      into Palestinian agricultural fields; and (4) in 2011, a person was sentenced to
      prison after threatening US and UK livestock with the deliberate spread of foot
      and-mouth disease virus. All 4 cases can be assigned to political groups. These
      cases have not attracted much attention in literature nor in the public media,
      and the credibility of the sources of information varies. We concluded that
      agroterrorism has not been a problem during the period studied. Lessons learned
      from the few cases have generated awareness about the fact that nontypical
      biological weapons and non-high-risk agents, such as African milk bush,
      screwworm, and sewer water, have been used by attackers to influence local
      decision makers. This review will be useful in improving future preparedness
      planning and developing countermeasures. 

PMID- 23971804
TI  - Animal botulism outcomes in the AniBioThreat project.
AB  - Botulism disease in both humans and animals is a worldwide concern. Botulinum
      neurotoxins produced by Clostridium botulinum and other Clostridium species are
      the most potent biological substances known and are responsible for flaccid
      paralysis leading to a high mortality rate. Clostridium botulinum and botulinum
      neurotoxins are considered potential weapons for bioterrorism and have been
      included in the Australia Group List of Biological Agents. In 2010 the European
      Commission (DG Justice, Freedom and Security) funded a 3-year project named
      AniBioThreat to improve the EU's capacity to counter animal bioterrorism threats.
      A detection portfolio with screening methods for botulism agents and incidents
      was needed to improve tracking and tracing of accidental and deliberate
      contamination of the feed and food chain with botulinum neurotoxins and other
      Clostridia. The complexity of this threat required acquiring new genetic
      information to better understand the diversity of these Clostridia and develop
      detection methods targeting both highly specific genetic markers of these
      Clostridia and the neurotoxins they are able to produce. Several European
      institutes participating in the AniBioThreat project collaborated on this program
      to achieve these objectives. Their scientific developments are discussed here. 

PMID- 23971805
TI  - The workshop on animal botulism in Europe.
AB  - A workshop on animal botulism was held in Uppsala, Sweden, in June 2012. Its
      purpose was to explore the current status of the disease in Europe by gathering
      the European experts in animal botulism and to raise awareness of the disease
      among veterinarians and others involved in biopreparedness. Animal botulism is
      underreported and underdiagnosed, but an increasing number of reports, as well as
      the information gathered from this workshop, show that it is an emerging problem
      in Europe. The workshop was divided into 4 sessions: animal botulism in Europe,
      the bacteria behind the disease, detection and diagnostics, and European
      collaboration and surveillance. An electronic survey was conducted before the
      workshop to identify the 3 most needed discussion points, which were: prevention,
      preparedness and outbreak response; detection and diagnostics; and European
      collaboration and surveillance. The main conclusions drawn from these discussions
      were that there is an urgent need to replace the mouse bioassay for botulinum
      toxin detection with an in vitro test and that there is a need for a European
      network to function as a reference laboratory, which could also organize a
      European supply of botulinum antitoxin and vaccines. The foundation of such a
      network was discussed, and the proposals are presented here along with the
      outcome of discussions and a summary of the workshop itself. 

PMID- 23971806
TI  - Management of animal botulism outbreaks: from clinical suspicion to practical
      countermeasures to prevent or minimize outbreaks.
AB  - Botulism is a severe neuroparalytic disease that affects humans, all warm-blooded
      animals, and some fishes. The disease is caused by exposure to toxins produced by
      Clostridium botulinum and other botulinum toxin-producing clostridia. Botulism in
      animals represents a severe environmental and economic concern because of its
      high mortality rate. Moreover, meat or other products from affected animals
      entering the food chain may result in a public health problem. To this end, early
      diagnosis is crucial to define and apply appropriate veterinary public health
      measures. Clinical diagnosis is based on clinical findings eliminating other
      causes of neuromuscular disorders and on the absence of internal lesions observed
      during postmortem examination. Since clinical signs alone are often insufficient
      to make a definitive diagnosis, laboratory confirmation is required. Botulinum
      antitoxin administration and supportive therapies are used to treat sick animals.
      Once the diagnosis has been made, euthanasia is frequently advisable. Vaccine
      administration is subject to health authorities' permission, and it is restricted
      to a small number of animal species. Several measures can be adopted to prevent
      or minimize outbreaks. In this article we outline all phases of management of
      animal botulism outbreaks occurring in wet wild birds, poultry, cattle, horses,
      and fur farm animals. 

PMID- 23971807
TI  - Evaluation of DNA extraction methods suitable for PCR-based detection and
      genotyping of Clostridium botulinum.
AB  - Sufficient quality and quantity of extracted DNA is critical to detecting and
      performing genotyping of Clostridium botulinum by means of PCR-based methods. An
      ideal extraction method has to optimize DNA yield, minimize DNA degradation,
      allow multiple samples to be extracted, and be efficient in terms of cost, time,
      labor, and supplies. Eleven botulinum toxin-producing clostridia strains and 25
      samples (10 food, 13 clinical, and 2 environmental samples) naturally
      contaminated with botulinum toxin-producing clostridia were used to compare 4 DNA
      extraction procedures: Chelex((r)) 100 matrix, Phenol-Cloroform-Isoamyl alcohol,
      NucliSENS((r)) magnetic extraction kit, and DNeasy((r)) Blood & Tissue kit.
      Integrity, purity, and amount of amplifiable DNA were evaluated. The results show
      that the DNeasy((r)) Blood & Tissue kit is the best extraction method evaluated
      because it provided the most pure, intact, and amplifiable DNA. However,
      Chelex((r)) 100 matrix seems to be suitable for PCR-based methods intended for
      laboratory diagnosis of suspected outbreaks of botulism, because it is faster and
      cheaper compared to DNeasy((r)) Blood & Tissue kit, and for samples in which the
      mean of Ct values obtained are statistically different (P>0.05) with respect to
      the best method, no lack of PCR amplification was shown. In addition, molecular
      methods for laboratory diagnosis currently are based on a microbial enrichment
      step prior to PCR, and so the differences in amplification seem to not influence
      the analytical results. 

PMID- 23971808
TI  - Multiplex real-time PCR for detecting and typing Clostridium botulinum group III
      organisms and their mosaic variants.
AB  - Botulism is a neuroparalytic disease that can occur in all warm-blooded animals,
      birds, and fishes. The disease in animals is mainly caused by toxins produced by
      Clostridium botulinum strains belonging to group III, although outbreaks due to
      toxins produced by group I and II organisms have been recognized. Group III
      strains are capable of producing botulinum toxins of type C, D, and C/D and D/C
      mosaic variants. Definitive diagnosis of animal botulism is made by combining
      clinical findings with laboratory investigations. Detection of toxins in clinical
      specimens and feed is the gold standard for laboratory diagnosis. Since toxins
      may be degraded by organisms contained in the gastrointestinal tract or may be
      present at levels below the detection limit, the recovery of C. botulinum from
      sick animal specimens is consistent for laboratory confirmation. In this article
      we report the development and in-house validation of a new multiplex real-time
      PCR for detecting and typing the neurotoxin genes found in C. botulinum group III
      organisms. Validation procedures have been carried out according to ISO 16140,
      using strains and samples recovered from cases of animal botulism in Italy and
      France. 

PMID- 23971809
TI  - Mass spectrometric detection of protein-based toxins.
AB  - This review focuses on mass spectrometric detection of protein-based toxins,
      which are among the most toxic substances known. Special emphasis is given to the
      bacterial toxins botulinum neurotoxin from Clostridium botulinum and anthrax
      toxins from Bacillus anthracis as well as the plant toxin ricin produced by
      Ricinus communis. A common feature, apart from their extreme toxicity, is that
      they are composed of 2 polypeptide chains, one of which is responsible for cell
      uptake and another that has enzymatic function with the ability to destroy basic
      cellular functions. These toxins pose a threat, both regarding natural spread and
      from a terrorism perspective. In order for public health and emergency response
      officials to take appropriate action in case of an outbreak, whether natural or
      intentional, there is a need for fast and reliable detection methods.
      Traditionally, large molecules like proteins have been detected using
      immunological techniques. Although sensitive, these methods suffer from some
      drawbacks, such as the risk of false-positives due to cross-reactions and
      detection of inactive toxin. This article describes recently developed
      instrumental methods based on mass spectrometry for the reliable detection of
      botulinum neurotoxins, anthrax toxins, and ricin. Unequivocal identification of a
      protein toxin can be carried out by mass spectrometry-based amino acid
      sequencing. Furthermore, in combination with antibody affinity preconcentration
      and biochemical tests with mass spectrometric detection demonstrating the toxin's
      enzymatic activity, very powerful analytical methods have been described. In
      conclusion, the advent of sensitive, easily operated mass spectrometers provides
      new possibilities for the detection of protein-based toxins. 

PMID- 23971810
TI  - The effect of preprocessing by sequence-independent, single-primer amplification
      (SISPA) on metagenomic detection of viruses.
AB  - Compared to routine diagnostics, screening for pathogens in outbreak situations,
      with or without intentional release, poses demands on the detection technology to
      not only indicate the presence of already known causative agents but also novel
      and unexpected pathogens. The metagenomic approach to detecting viral pathogens,
      using unbiased high-throughput sequencing (HTS), is a well-established
      methodology with a broad detection range and wide applicability on different
      sample matrices. To prepare a sample for HTS, the common presequencing steps
      include homogenization, enrichment, separation (eg, magnetic separation), and
      amplification. In this initial study, we explored the benefits and drawbacks of
      preprocessing by sequence-independent, single-primer amplification (SISPA) of
      nucleic acids by applying the methodology to artificial samples. More
      specifically, a synthetic metagenome was divided into 2 samples, 1 unamplified
      and 1 diluted, and amplified by SISPA. Subsequently, both samples were sequenced
      using the Ion Torrent Personal Genome Machine (PGM), and the resulting datasets
      were analyzed by using bioinformatics, short read mapping, de novo assembly,
      BLAST-based taxonomic classification, and visualization. The results indicate
      that even though SISPA introduces a strong amplification bias, which makes it
      unsuitable for whole-genome sequencing, it is still useful for detecting and
      identifying viruses. 

PMID- 23971811
TI  - Development and optimization of a biopreparedness protocol for extracting and
      detecting avian influenza virus in broiler chicken meat.
AB  - Detection of avian influenza virus (AIV) in poultry meat is hampered by the lack
      of an efficient analytical method able to extract and concentrate viral RNA prior
      to PCR. In this study we developed a method for extracting and detecting AIV from
      poultry meat by a previously standardized 1-step real-time reverse transcriptase
      PCR (RRT-PCR) assay. In addition, a new process control, represented by feline
      calicivirus (FCV), was included in the original protocol, to evaluate all
      analytical steps from sample preparation to the detection phase. The detection
      limit was below 1*10(-1) TCID50 of AIV per sample, and the quantification limit
      corresponded to 1*10(1) TCID50 of AIV per sample. Moreover, the addition of
      1*10(2) TCID50/sample of FCV did not affect the quantification and detection
      limit of the reaction. These results show that the developed assay is suitable
      for detecting small amounts of AIV in poultry meat. In addition, the developed
      biopreparedness protocol can be applied to detect AIV in legal or illegal
      imported broiler chicken meat. The availability of a rapid and sensitive
      diagnostic method based on molecular identification of AIV in poultry meat
      provides an important tool in the prevention of AIV circulation. 

PMID- 23971812
TI  - Review of a new molecular virus pathotyping method in the context of
      bioterrorism.
AB  - Avian influenza virus (AIV) and Newcastle disease virus (NDV) infect various
      avian species including domestic poultry. Clinical manifestations vary from
      subclinical or mild to severe multiorgan systemic disease with a near 100%
      mortality rate. Severe disease is caused by highly virulent specific virus
      strains, termed highly pathogenic AIV and velogenic NDV. Recent controversial
      influenza H5 adaptation studies in ferrets have highlighted the importance of
      preparedness against AIV as a bioterrorism agent. Furthermore, NDV also has
      zoonotic potential, although symptoms in humans are mild and self-limiting for
      naturally occurring viruses. Thus, both of these viruses pose a direct biothreat
      to domestic poultry but also indirectly to humans via zoonotic transmission. For
      diagnosis and rapid containment of disease, it is crucial to differentiate highly
      pathogenic AIVs and NDVs from frequently occurring low pathogenic variants.
      Recently, we developed a novel strategy for pathotyping of AIV and NDV that we
      review here. The method should be ideal for rapid testing and surveillance in
      food safety, for wild bird monitoring, and for combating acts of bioterrorism. 

PMID- 23971813
TI  - Rodents as potential couriers for bioterrorism agents.
AB  - Many pathogens that can cause major public health, economic, and social damage
      are relatively easily accessible and could be used as biological weapons.
      Wildlife is a natural reservoir for many potential bioterrorism agents, and, as
      history has shown, eliminating a pathogen that has dispersed among wild fauna can
      be extremely challenging. Since a number of wild rodent species live close to
      humans, rodents constitute a vector for pathogens to circulate among wildlife,
      domestic animals, and humans. This article reviews the possible consequences of a
      deliberate spread of rodentborne pathogens. It is relatively easy to infect wild
      rodents with certain pathogens or to release infected rodents, and the action
      would be difficult to trace. Rodents can also function as reservoirs for diseases
      that have been spread during a bioterrorism attack and cause recurring disease
      outbreaks. As rats and mice are common in both urban and rural settlements,
      deliberately released rodentborne infections have the capacity to spread very
      rapidly. The majority of pathogens that are listed as potential agents of
      bioterrorism by the Centers for Disease Control and Prevention and the National
      Institute of Allergy and Infectious Diseases exploit rodents as vectors or
      reservoirs. In addition to zoonotic diseases, deliberately released rodentborne
      epizootics can have serious economic consequences for society, for example, in
      the area of international trade restrictions. The ability to rapidly detect
      introduced diseases and effectively communicate with the public in crisis
      situations enables a quick response and is essential for successful and cost
      effective disease control. 

PMID- 23971814
TI  - Agroterrorism targeting livestock: a review with a focus on early detection
      systems.
AB  - Agroterrorism targeting livestock can be described as the intentional
      introduction of an animal disease agent against livestock with the purpose of
      causing economic damage, disrupting socioeconomic stability of a country, and
      creating panic and distress. This type of terrorism can be alluring to terrorists
      because animal disease agents are easily available. This review addresses the
      vulnerabilities of the livestock industry to agroterrorism. However, we also show
      that early detection systems have recently been developed for agroterrorism and
      deliberate spread of animal pathogens in livestock, including an agroterrorism
      intelligence cycle, syndromic surveillance programs, and computer-based clinical
      decision support systems that can be used for early detection of notifiable
      animal diseases. The development of DIVA-vaccines in the past 10 to 15 years has
      created, in principle, an excellent response instrument to counter intentional
      animal disease outbreaks. These developments have made our animal agriculture
      less vulnerable to agroterrorism. But we cannot relax; there are still many
      challenges, in particular with respect to integration of first line of defense,
      law enforcement, and early detection systems for animal diseases. 

PMID- 23971815
TI  - From interblocking stovepipes to interlocking networks.

PMID- 23971816
TI  - Knowledge communication: a key to successful crisis management.
AB  - A winning concept of crisis management can be summarized in 2 words: knowledge
      communication. If decision makers, communicators, experts, and the public
      understand what the crisis is about and share their knowledge, the process of
      handling it will be optimized. Effective crisis communication implies the
      necessity of an unhindered but purposeful exchange of information within and
      between authorities, organizations, media, involved individuals, and groups
      before, during, and after a crisis. This article focuses on the importance of the
      before, or prevention, part of a crisis since it holds a rich possibility to
      enhance the chances for successful crisis management of a bioterrorism incident.
      An extended perspective on crisis communication efficiently links to a more
      thorough understanding of risk perception with various stakeholders and the
      public, which also will be helpful for situational awareness. Furthermore, the
      grounded baseline for the dialogue type of crisis communication suitable in
      modern society and to modern social media is achieved by linking to those risk
      communication efforts that are made. The link between risk and crisis should be
      afforded more attention since, especially in biosecurity, there would be no
      crisis without risk negligence and poor or malfunctioning preventive efforts. 

PMID- 23971817
TI  - Social media and its dual use in biopreparedness: communication and visualization
      tools in an animal bioterrorism incident.
AB  - This article focuses on social media and interactive challenges for emergency
      organizations during a bioterrorism or agroterrorism incident, and it outlines
      the dual-use dilemma of social media. Attackers or terrorists can use social
      media as their modus operandi, and defenders, including emergency organizations
      in law enforcement and public and animal health, can use it for peaceful
      purposes. To get a better understanding of the uses of social media in these
      situations, a workshop was arranged in Stockholm, Sweden, to raise awareness
      about social media and animal bioterrorism threats. Fifty-six experts and crisis
      communicators from international and national organizations participated. As a
      result of the workshop, it was concluded that emergency organizations can collect
      valuable information and monitor social media before, during, and after an
      outbreak. In order to make use of interactive communication to obtain collective
      intelligence from the public, emergency organizations must adapt to social
      networking technologies, requiring multidisciplinary knowledge in the fields of
      information, communication, IT, and biopreparedness. Social network messaging
      during a disease outbreak can be visualized in stream graphs and networks showing
      clusters of Twitter and Facebook users. The visualization of social media can be
      an important preparedness tool in the response to bioterrorism and agroterrorism.

PMID- 23971818
TI  - Separated by a common language: awareness of term usage differences between
      languages and disciplines in biopreparedness.
AB  - Preparedness for bioterrorism is based on communication between people in
      organizations who are educated and trained in several disciplines, including law
      enforcement, health, and science. Various backgrounds, cultures, and vocabularies
      generate difficulties in understanding and interpretating terms and concepts,
      which may impair communication. This is especially true in emergency situations,
      in which the need for clarity and consistency is vital. The EU project
      AniBioThreat initiated methods and made a rough estimate of the terms and
      concepts that are crucial for an incident, and a pilot database with key terms
      and definitions has been constructed. Analysis of collected terms and sources has
      shown that many of the participating organizations use various international
      standards in their area of expertise. The same term often represents different
      concepts in the standards from different sectors, or, alternatively, different
      terms were used to represent the same or similar concepts. The use of conflicting
      terminology can be problematic for decision makers and communicators in planning
      and prevention or when handling an incident. Since the CBRN area has roots in
      multiple disciplines, each with its own evolving terminology, it may not be
      realistic to achieve unequivocal communication through a standardized vocabulary
      and joint definitions for words from common language. We suggest that a
      communication strategy should include awareness of alternative definitions and
      ontologies and the ability to talk and write without relying on the implicit
      knowledge underlying specialized jargon. Consequently, cross-disciplinary
      communication skills should be part of training of personnel in the CBRN field.
      In addition, a searchable repository of terms and definitions from relevant
      organizations and authorities would be a valuable addition to existing glossaries
      for improving awareness concerning bioterrorism prevention planning. 

PMID- 23971819
TI  - Development of a comparative risk ranking system for agents posing a bioterrorism
      threat to human or animal populations.
AB  - Various systems for prioritizing biological agents with respect to their
      applicability as biological weapons are available, ranging from qualitative to
      (semi)quantitative approaches. This research aimed at generating a generic risk
      ranking system applicable to human and animal pathogenic agents based on
      scientific information. Criteria were evaluated and clustered to create a
      criteria list. Considering availability of data, a number of 28 criteria
      separated by content were identified that can be classified in 11 thematic areas
      or categories. Relevant categories contributing to probability were historical
      aspects, accessibility, production efforts, and possible paths for dispersion.
      Categories associated with impact are dealing with containment measures,
      availability of diagnostics, preventive and treatment measures in human and
      animal populations, impact on society, human and veterinary public health, and
      economic and ecological consequences. To allow data-based scoring, each criterion
      was described by at least 1 measure that allows the assignment of values. These
      values constitute quantities, ranges, or facts that are as explicit and precise
      as possible. The consideration of minimum and maximum values that can occur due
      to natural variations and that are often described in the literature led to the
      development of minimum and maximum criteria and consequently category scores.
      Missing or incomplete data, and uncertainty resulting therefrom, were integrated
      into the scheme via a cautious (but not overcautious) approach. The visualization
      technique that was used allows the description and illustration of uncertainty on
      the level of probability and impact. The developed risk ranking system was
      evaluated by assessing the risk originating from the bioterrorism threat of the
      animal pathogen bluetongue virus, the human pathogen Enterohemorrhagic
      Escherichia coli O157:H7, the zoonotic Bacillus anthracis, and Botulinum
      neurotoxin. 

PMID- 23971820
TI  - Harmonization of European laboratory response networks by implementing CWA 15793:
      use of a gap analysis and an "insider" exercise as tools.
AB  - Laboratory response networks (LRNs) have been established for security reasons in
      several countries including the Netherlands, France, and Sweden. LRNs function in
      these countries as a preparedness measure for a coordinated diagnostic response
      capability in case of a bioterrorism incident or other biocrimes. Generally,
      these LRNs are organized on a national level. The EU project AniBioThreat has
      identified the need for an integrated European LRN to strengthen preparedness
      against animal bioterrorism. One task of the AniBioThreat project is to suggest a
      plan to implement laboratory biorisk management CWA 15793:2011 (CWA 15793), a
      management system built on the principle of continual improvement through the
      Plan-Do-Check-Act (PDCA) cycle. The implementation of CWA 15793 can facilitate
      trust and credibility in a future European LRN and is an assurance that the work
      done at the laboratories is performed in a structured way with continuous
      improvements. As a first step, a gap analysis was performed to establish the
      current compliance status of biosafety and laboratory biosecurity management with
      CWA 15793 in 5 AniBioThreat partner institutes in France (ANSES), the Netherlands
      (CVI and RIVM), and Sweden (SMI and SVA). All 5 partners are national and/or
      international laboratory reference institutes in the field of public or animal
      health and possess high-containment laboratories and animal facilities. The gap
      analysis showed that the participating institutes already have robust biorisk
      management programs in place, but several gaps were identified that need to be
      addressed. Despite differences between the participating institutes in their
      compliance status, these variations are not significant. Biorisk management
      exercises also have been identified as a useful tool to control compliance status
      and thereby implementation of CWA 15793. An exercise concerning an insider threat
      and loss of a biological agent was performed at SVA in the AniBioThreat project
      to evaluate implementation of the contingency plans and as an activity in the
      implementation process of CWA 15793. The outcome of the exercise was perceived as
      very useful, and improvements to enhance biorisk preparedness were identified.
      Gap analyses and exercises are important, useful activities to facilitate
      implementation of CWA 15793. The PDCA cycle will enforce a structured way to
      work, with continual improvements concerning biorisk management activities. Based
      on the activities in the AniBioThreat project, the following requirements are
      suggested to promote implementation: support from the top management of the
      organizations, knowledge about CWA 15793, a compliance audit checklist and gap
      analysis, training and exercises, networking in LRNs and other networks, and
      interinstitutional audits. Implementation of CWA 15793 at each institute would
      strengthen the European animal bioterrorism response capabilities by establishing
      a well-prepared LRN. 

PMID- 23971821
TI  - Improved CBRN preparedness and response through teamwork and knowledge sharing.

PMID- 23971822
TI  - Actionable knowledge and strategic decision making for bio- and agroterrorism
      threats: building a collaborative early warning culture.
AB  - Current trends in biosecurity and cybersecurity include (1) the wide availability
      of technology and specialized knowledge that previously were available only to
      governments; (2) the global economic recession, which may increase the spread of
      radical non-state actors; and (3) recent US and EU commission reports that
      reflect concerns about non-state actors in asymmetric threats. The intersectoral
      and international nature of bioterrorism and agroterrorism threats requires
      collaboration across several sectors including intelligence, police, forensics,
      customs, and other law enforcement organizations who must work together with
      public and animal health organizations as well as environmental and social
      science organizations. This requires coordinated decision making among these
      organizations, based on actionable knowledge and information sharing. The risk of
      not sharing information among organizations compared to the benefit of sharing
      information can be considered in an "information sharing risk-benefit analysis"
      to prevent a terrorism incident from occurring and to build a rapid response
      capability. In the EU project AniBioThreat, early warning is the main topic in
      work package 3 (WP 3). A strategy has been generated based on an iterative
      approach to bring law enforcement agencies and human and animal health institutes
      together. Workshops and exercises have taken place during the first half of the
      project, and spin-off activities include new preparedness plans for institutes
      and the formation of a legal adviser network for decision making. In addition, a
      seminar on actionable knowledge was held in Stockholm, Sweden, in 2012, which
      identified the need to bring various agency cultures together to work on
      developing a resilient capability to identify early signs of bio- and
      agroterrorism threats. The seminar concluded that there are a number of
      challenges in building a collaborative culture, including developing an education
      program that supports collaboration and shared situational awareness. 

PMID- 23971823
TI  - Dealing with future risks in the Netherlands.
AB  - The national security strategy is the Dutch government's instrument for
      multihazard risk management and is intended to contribute to the prevention of
      societal disruption as a consequence of a (future) disaster or crisis in the
      Netherlands. It considers the likelihood that a certain incident will occur, the
      impact if it should occur, and what can be done to prevent the occurrence and/or
      reduce the impact. In other words, "which threats is the Netherlands faced with,
      how serious are they, and what can be done to mitigate the consequences?" By
      annually assessing the likelihood and impact of different scenarios, the
      government is able to continually improve its overview of risks and to determine
      priorities regarding the allocation of resources for the prevention of,
      preparation for, and response to threats. At the start of the annual cycle of the
      implementation of the national security strategy, possible scenarios are
      identified. These scenarios are then drawn up and assessed by the Network of
      Analysts for National Security, resulting in the national risk assessment (NRA).
      On the basis of this risk assessment, a capabilities analysis is performed. This
      capabilities analysis assesses whether the country (government, private sector,
      and civilians) has sufficient capabilities (people, material, knowledge, skills,
      and procedures) at its disposal to adequately deal with the threat, and it
      considers which capabilities should be strengthened or developed. Finally, a
      report is prepared for the council of ministers. On the basis of this report, the
      cabinet decides which capabilities will be strengthened.

PMID- 23971824
TI  - Bayesian networks for evaluation of evidence from forensic entomology.
AB  - In the aftermath of a CBRN incident, there is an urgent need to reconstruct
      events in order to bring the perpetrators to court and to take preventive actions
      for the future. The challenge is to discriminate, based on available information,
      between alternative scenarios. Forensic interpretation is used to evaluate to
      what extent results from the forensic investigation favor the prosecutors' or the
      defendants' arguments, using the framework of Bayesian hypothesis testing.
      Recently, several new scientific disciplines have been used in a forensic
      context. In the AniBioThreat project, the framework was applied to veterinary
      forensic pathology, tracing of pathogenic microorganisms, and forensic
      entomology. Forensic entomology is an important tool for estimating the
      postmortem interval in, for example, homicide investigations as a complement to
      more traditional methods. In this article we demonstrate the applicability of the
      Bayesian framework for evaluating entomological evidence in a forensic
      investigation through the analysis of a hypothetical scenario involving suspect
      movement of carcasses from a clandestine laboratory. Probabilities of different
      findings under the alternative hypotheses were estimated using a combination of
      statistical analysis of data, expert knowledge, and simulation, and entomological
      findings are used to update the beliefs about the prosecutors' and defendants'
      hypotheses and to calculate the value of evidence. The Bayesian framework proved
      useful for evaluating complex hypotheses using findings from several insect
      species, accounting for uncertainty about development rate, temperature, and
      precolonization. The applicability of the forensic statistic approach to
      evaluating forensic results from a CBRN incident is discussed. 

PMID- 23971825
TI  - The need for high-quality whole-genome sequence databases in microbial forensics.
AB  - Microbial forensics is an important part of a strengthened capability to respond
      to biocrime and bioterrorism incidents to aid in the complex task of
      distinguishing between natural outbreaks and deliberate acts. The goal of a
      microbial forensic investigation is to identify and criminally prosecute those
      responsible for a biological attack, and it involves a detailed analysis of the
      weapon--that is, the pathogen. The recent development of next-generation
      sequencing (NGS) technologies has greatly increased the resolution that can be
      achieved in microbial forensic analyses. It is now possible to identify, quickly
      and in an unbiased manner, previously undetectable genome differences between
      closely related isolates. This development is particularly relevant for the most
      deadly bacterial diseases that are caused by bacterial lineages with extremely
      low levels of genetic diversity. Whole-genome analysis of pathogens is envisaged
      to be increasingly essential for this purpose. In a microbial forensic context,
      whole-genome sequence analysis is the ultimate method for strain comparisons as
      it is informative during identification, characterization, and attribution--all 3
      major stages of the investigation--and at all levels of microbial strain identity
      resolution (ie, it resolves the full spectrum from family to isolate). Given
      these capabilities, one bottleneck in microbial forensics investigations is the
      availability of high-quality reference databases of bacterial whole-genome
      sequences. To be of high quality, databases need to be curated and accurate in
      terms of sequences, metadata, and genetic diversity coverage. The development of
      whole-genome sequence databases will be instrumental in successfully tracing
      pathogens in the future.

PMID- 23971826
TI  - Pre-PCR processing in bioterrorism preparedness: improved diagnostic capabilities
      for laboratory response networks.
AB  - Diagnostic DNA analysis using polymerase chain reaction (PCR) has become a
      valuable tool for rapid detection of biothreat agents. However, analysis is often
      challenging because of the limited size, quality, and purity of the biological
      target. Pre-PCR processing is an integrated concept in which the issues of
      analytical limit of detection and simplicity for automation are addressed in all
      steps leading up to PCR amplification--that is, sampling, sample treatment, and
      the chemical composition of PCR. The sampling method should maximize target
      uptake and minimize uptake of extraneous substances that could impair the
      analysis--so-called PCR inhibitors. In sample treatment, there is a trade-off
      between yield and purity, as extensive purification leads to DNA loss. A
      cornerstone of pre-PCR processing is to apply DNA polymerase-buffer systems that
      are tolerant to specific sample impurities, thereby lowering the need for
      expensive purification steps and maximizing DNA recovery. Improved awareness
      among Laboratory Response Networks (LRNs) regarding pre-PCR processing is
      important, as ineffective sample processing leads to increased cost and possibly
      false-negative or ambiguous results, hindering the decision-making process in a
      bioterrorism crisis. This article covers the nature and mechanisms of PCR
      inhibitory substances relevant for agroterrorism and bioterrorism preparedness,
      methods for quality control of PCR reactions, and applications of pre-PCR
      processing to optimize and simplify the analysis of various biothreat agents.
      Knowledge about pre-PCR processing will improve diagnostic capabilities of LRNs
      involved in the response to bioterrorism incidents.

PMID- 23971827
TI  - Synthesis, electronic structure, and magnetism of [Ni(6-Mes)2]+: a two-coordinate
      nickel(I) complex stabilized by bulky N-heterocyclic carbenes.
AB  - The two-coordinate cationic Ni(I) bis-N-heterocyclic carbene complex [Ni(6
      Mes)2]Br (1) [6-Mes =1,3-bis(2,4,6-trimethylphenyl)-3,4,5,6-tetrahydropyrimidin-2
      ylidene] has been structurally characterized and displays a highly linear
      geometry with a C-Ni-C angle of 179.27(13) degrees . Density functional theory
      calculations revealed that the five occupied metal-based orbitals are split in an
      approximate 2:1:2 pattern. Significant magnetic anisotropy results from this
      orbital degeneracy, leading to single-ion magnet (SIM) behavior. 

PMID- 23971828
TI  - The OTSC(r) Proctology clip system for anal fistula closure: first prospective
      clinical data.
AB  - INTRODUCTION: Anorectal fistulas represent a troublesome condition for both
      patient and surgeon. The OTSC(r) Proctology clip system is a new device for
      transanal anorectal fistula closure. MATERIAL AND METHODS: The OTSC(r) Proctology
      system was evaluated in a prospective clinical study undertaken in two surgical
      proctological centers. Ten patients (three women, seven men; median age 55 years,
      range 25-73 years) with nine transsphincteric and one suprasphincteric fistulas
      were enrolled into the study. RESULTS: The median operation time was 30 minutes
      (range 20-45 minutes). There were no intraoperative technical or surgical
      complications. Postoperatively, no patient reported intolerable discomfort,
      immoderate pain or foreign body sensation in the anal region. At follow-up
      examination six months after surgery, nine out of ten patients had no clinical
      signs or symptoms of their previous fistula and were considered as healed
      (success rate 90%). In one patient persistency of the fistula was noted due to
      spontaneous early clip detachment on the third postoperative day. DISCUSSION:
      These first data demonstrate the efficacy of the OTSC(r) Proctology system in the
      treatment of anal fistulas. Currently, more patients were enrolled into this
      prospective study to allow further evaluation of this new device and to assess
      its future role in relation to established surgical strategies for anorectal
      fistulas.

PMID- 23971829
TI  - Ridaforolimus in advanced or metastatic soft tissue and bone sarcomas.
AB  - Patient outcomes remain poor for advanced or metastatic soft tissue sarcomas
      (STS) and bone sarcomas despite a growing number of clinical trials involving
      single- and multi-agent chemotherapy. mTOR is an intracellular kinase that plays
      a central role in regulating cell growth, metabolism, survival and proliferation.
      mTOR inhibitors including temsirolimus, everolimus and ridaforolimus have
      demonstrated broad anticancer activity. Ridaforolimus is a non-prodrug analog of
      rapamycin (sirolimus) with conserved affinity for mTOR but improved solubility,
      stability and bioavailability when compared with sirolimus. Early clinical trials
      reveal a reproducible and predictable pharmacokinetic profile, a potent, rapid
      and prolonged target inhibition and an acceptable safety and tolerability
      profile. Phase II and III trials of ridaforolimus have produced promising
      clinical activity against advanced sarcomas and will be presented. 

PMID- 23971830
TI  - Effect of permeable biofilm on micro- and macro-scale flow and transport in
      bioclogged pores.
AB  - Simulations of coupled flow around and inside biofilms in pores were conducted to
      study the effect of porous biofilm on micro- and macro-scale flow and transport.
      The simulations solved the Navier-Stokes equations coupled with the Brinkman
      equation representing flow in the pore space and biofilm, respectively, and the
      advection-diffusion equation. Biofilm structure and distribution were obtained
      from confocal microscope images. The bulk permeability (k) of bioclogged porous
      media depends on biofilm permeability (kbr) following a sigmoidal curve on a log
      log scale. The upper and lower limits of the curve are the k of biofilm-free
      media and of bioclogged media with impermeable biofilms, respectively. On the
      basis of this, a model is developed that predicts k based solely on kbr and
      biofilm volume ratio. The simulations show that kbr has a significant impact on
      the shear stress distribution, and thus potentially affects biofilm erosion and
      detachment. The sensitivity of flow fields to kbr directly translated to effects
      on the transport fields by affecting the relative distribution of where advection
      and diffusion dominated. Both kbr and biofilm volume ratio affect the shape of
      breakthrough curves. 

PMID- 23971831
TI  - The polar mechanism for the nitration of benzene with nitronium ion: ab initio
      structures of intermediates and transition states.
AB  - The nitration of benzene by nitronium ion in the gas phase has been re-examined.
      New features have been revealed; in particular, three transition states have been
      detected along the reaction coordinate. These have been shown by IRC analysis to
      connect an initially formed pi complex (pi1) to a sigma complex (sig1) (via ts1),
      sig1 to sig2 (via ts2), and finally sig2 to the product (via ts3). Sig2 also
      connects to another isomeric sigma complex sig3 (via sig23ts), which connects to
      sig4 (via sig34ts). 

PMID- 23971833
TI  - In vitro hematopoiesis reveals a novel dendritic-like cell present in murine
      spleen.
AB  - Dendritic cells (DC) are important antigen presenting cells (APC) which induce
      and control the adaptive immune response. In spleen alone, multiple DC subsets
      can be distinguished by cell surface marker phenotype. Most of these have been
      shown to develop from progenitors in bone marrow and to seed lymphoid and tissue
      sites during development. This study advances in vitro methodology for
      hematopoiesis of dendritic-like cells from progenitors in spleen. Since spleen
      progenitors undergo differentiation in vitro to produce these cells, the
      possibility exists that spleen represents a specific niche for differentiation of
      this subset. The fact that an equivalent cell subset has been shown to exist in
      spleen also supports that hypothesis. Studies have been directed at investigating
      the specific functional role of this novel subset as an APC accessible to blood
      borne antigen, as well as the conditions under which hematopoiesis is initiated
      in spleen, and the type of progenitor involved. 

PMID- 23971832
TI  - Pharmacologic reversion of epigenetic silencing of the PRKD1 promoter blocks
      breast tumor cell invasion and metastasis.
AB  - INTRODUCTION: DNA methylation-induced silencing of genes encoding tumor
      suppressors is common in many types of cancer, but little is known about how such
      epigenetic silencing can contribute to tumor metastasis. The PRKD1 gene encodes
      protein kinase D1 (PKD1), a serine/threonine kinase that is expressed in cells of
      the normal mammary gland, where it maintains the epithelial phenotype by
      preventing epithelial-to-mesenchymal transition. METHODS: The status of PRKD1
      promoter methylation was analyzed by reduced representation bisulfite deep
      sequencing, methylation-specific PCR (MSP-PCR) and in situ MSP-PCR in invasive
      and noninvasive breast cancer lines, as well as in humans in 34 cases of "normal"
      tissue, 22 cases of ductal carcinoma in situ, 22 cases of estrogen receptor
      positive, HER2-negative (ER+/HER2-) invasive lobular carcinoma, 43 cases of
      ER+/HER2- invasive ductal carcinoma (IDC), 93 cases of HER2+ IDC and 96 cases of
      triple-negative IDC. A reexpression strategy using the DNA methyltransferase
      inhibitor decitabine was used in vitro in MDA-MB-231 cells as well as in vivo in
      a tumor xenograft model and measured by RT-PCR, immunoblotting and
      immunohistochemistry. The effect of PKD1 reexpression on cell invasion was
      analyzed in vitro by transwell invasion assay. Tumor growth and metastasis were
      monitored in vivo using the IVIS Spectrum Pre-clinical In Vivo Imaging System.
      RESULTS: Herein we show that the gene promoter of PRKD1 is aberrantly methylated
      and silenced in its expression in invasive breast cancer cells and during breast
      tumor progression, increasing with the aggressiveness of tumors. Using an animal
      model, we show that reversion of PRKD1 promoter methylation with the DNA
      methyltransferase inhibitor decitabine restores PKD1 expression and blocks tumor
      spread and metastasis to the lung in a PKD1-dependent fashion. CONCLUSIONS: Our
      data suggest that the status of epigenetic regulation of the PRKD1 promoter can
      provide valid information on the invasiveness of breast tumors and therefore
      could serve as an early diagnostic marker. Moreover, targeted upregulation of
      PKD1 expression may be used as a therapeutic approach to reverse the invasive
      phenotype of breast cancer cells.

PMID- 23971834
TI  - Current and future applications for stem cell therapies in spine surgery.
AB  - Spinal surgery involves the bone-cartilage-neural interface. It is a field of
      surgery that is rapidly changing and evolving; not only through the development
      of novel techniques, approaches and devices but also through evidence from large
      clinical trials assessing indications, efficacy and outcomes. The use of
      biologics in spine surgery has now become widespread. Biologics in the form of
      autologous or allogeneic stem cells or progenitor cells are not yet in routine
      clinical use in spine surgery. However it is likely that they will have a
      significant role in the future, since increasing numbers of preclinical and
      clinical studies have demonstrated the safety and efficacy of progenitor cells to
      treat a variety of spinal conditions. Such studies have paved the way to larger
      clinical trials. Cell therapies encompass a wide range of stem cell and
      progenitor cell types. Stem cells subtypes differ in their lineage potential
      often being described as pluripotent or multipotent, some of which have potential
      application in therapies to treat diseases of the spine having the ability to
      differentiate into tissues including bone and cartilage and to secrete factors
      that promote matrix repair and regeneration. Furthermore, studies have shown that
      some cells, particularly mesenchymal stromal cells, modulate oxidative stress and
      secrete cytokines and growth factors that have immunomodulatory,
      antiinflammatory, angiogenic and antiapoptotic effects. It is these combined
      characteristics that make cell based therapies prime candidates for advancing
      current techniques in spine surgery and for providing new strategies directed at
      targeting the underlying causes of spinal diseases and disorders to promote
      repair and regeneration. This review will explore the characteristics of various
      stem cells and other progenitor cells derived from different sources. The authors
      are not suggesting that all these cells are necessarily suitable clinically. The
      review will thus focus on their application to both current and potentially
      future areas of spine surgery based on results of the available evidence and
      clinical trials. This review will not address spinal cord injury. 

PMID- 23971837
TI  - Employment of recent graduates.

PMID- 23971838
TI  - What is your diagnosis? Cecocolic intussesception in a horse.

PMID- 23971839
TI  - What is your diagnosis? Abdominal neoplasms in a cat.

PMID- 23971840
TI  - Diagnostic imaging in veterinary dental practice. Dental pulp disease in a river
      otter.

PMID- 23971841
TI  - ECG of the Month. Arrhythmia.

PMID- 23971842
TI  - Animal behavior case of the month. Fear behavior in a cat.

PMID- 23971843
TI  - Pathology in Practice. Multicentric B-cell lymphoma.

PMID- 23971844
TI  - Thiamine deficiency in dogs and cats.

PMID- 23971845
TI  - Evaluation of calcium, phosphorus, and selected trace mineral status in
      commercially available dry foods formulated for dogs.
AB  - OBJECTIVE: To evaluate concentrations of calcium, phosphorus, zinc, iron, copper,
      manganese, and selenium in several commercially available dry dog foods and
      compare these with current Association of American Feed Control Officials (AAFCO)
      recommendations for maintenance of healthy dogs. DESIGN: Descriptive study.
      SAMPLE: 45 over-the-counter dry foods formulated for maintenance of healthy dogs
      (ie, maintenance foods) and 5 therapeutic dry foods formulated for dogs with
      hepatic or renal disease. PROCEDURES: Mineral concentrations were measured via
      inductively coupled plasma mass spectrometry or inductively coupled plasma atomic
      emission spectroscopy and compared with AAFCO-recommended minimum and maximum
      values. RESULTS: Most (39/45) maintenance foods were in compliance with AAFCO
      recommendations for all mineral concentrations evaluated. Calcium concentration
      was > 7. 1 g/1,000 kcal of metabolizable energy (ME) in 4 of 45 maintenance
      foods, and phosphorus concentration was > 4.6 g/1,000 kcal ME in 3 of these; 2
      maintenance foods contained < 34 mg of zinc/1,000 kcal ME. These values were not
      within AAFCO-recommended ranges. Calcium-to-phosphorus ratio in foods formulated
      for dogs with renal disease was above, and copper concentration in foods
      formulated for dogs with hepatic disease was below, recommended ranges for
      healthy dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Calcium concentrations exceeded
      recommended limits in some maintenance foods labeled for all life stages,
      underscoring the need to feed diets appropriately formulated for specific life
      stages, particularly for large- and giant-breed puppies. Studies investigating
      the bioavailability of minerals are necessary before firm recommendations can be
      made.

PMID- 23971846
TI  - Characteristics of, prevalence of, and risk factors for corneal pigmentation
      (pigmentary keratopathy) in Pugs.
AB  - OBJECTIVE: To determine the characteristics of, prevalence of, and risk factors
      for corneal pigmentation (CP) in Pugs. DESIGN: Prospective cross-sectional study.
      ANIMALS: 295 Pugs > 16 weeks old. PROCEDURES: Ophthalmic examination of the
      anterior segment of each eye was performed, including determination of tear film
      characteristics (Schirmer tear test and tear film breakup time) and corneal
      sensitivity. Digital photographs of the head and each eye were obtained. Corneal
      pigmentation of eyes was graded as absent, very mild, mild, moderate, or severe.
      Signalment and medical history information and American Kennel Club registration
      status were recorded. Results-CP was detected in at least 1 eye of 243 of the 295
      (82.4%) Pugs; CP was typically very mild or mild. Detection of CP was not
      significantly associated with coat color, age, eyelid conformation, or tear film
      characteristics but was significantly associated with sex of dogs. The severity
      of CP was not significantly associated with American Kennel Club registration
      status or age, but was significantly associated with sex, tear film
      characteristics, and coat color. Iris hypoplasia was detected in 72.1% of the
      Pugs. Iris-to-iris persistent pupillary membranes were detected in 85.3% of the
      Pugs. CONCLUSIONS AND CLINICAL RELEVANCE: Prevalence of CP in Pugs in this study
      was high. Unexpectedly high prevalences of iris hypoplasia and persistent
      pupillary membranes were also identified. The condition identified in these Pugs
      was a pigmentary keratopathy, rather than pigmentary keratitis or corneal
      melanosis. This condition may have a genetic basis, and further studies are
      warranted to determine etiology.

PMID- 23971847
TI  - Comparison of lateral fabellar suture and tibial plateau leveling osteotomy
      techniques for treatment of dogs with cranial cruciate ligament disease.
AB  - OBJECTIVE: To compare 1-year outcomes after lateral fabellar suture stabilization
      (LFS) and tibial plateau leveling osteotomy (TPLO) for the treatment of dogs with
      cranial cruciate ligament disease. DESIGN: Randomized blinded controlled clinical
      trial. ANIMALS: 80 dogs with naturally occurring unilateral cranial cruciate
      ligament disease. PROCEDURES: All dogs were randomly assigned to undergo LFS (n =
      40) or TPLO (40). Clinical data collected included age, weight, body condition
      score, history information, stifle joint instability, radiographic findings,
      surgical findings, and complications. Outcome measures were determined prior to
      surgery and at 6 and 12 weeks and 6 and 12 months after surgery, including values
      of pressure platform gait analysis variables, Canine Brief Pain Inventory scores,
      owner satisfaction ratings, thigh circumference, and stifle joint goniometry
      values. RESULTS: Signalment and data for possible confounding variables were
      similar between groups. Peak vertical force of affected hind limbs at a walk and
      trot was 5% to 11% higher for dogs in the TPLO group versus those in the LFS
      group during the 12 months after surgery. Canine Brief Pain Inventory,
      goniometry, and thigh circumference results indicated dogs in both groups
      improved after surgery, but significant differences between groups were not
      detected. Owner satisfaction ratings at 12 months after surgery were
      significantly different between groups; 93% and 75% of owners of dogs in the TPLO
      and LFS groups indicated a satisfaction score >= 9 (scale, 1 to 10),
      respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Kinematic and owner
      satisfaction results indicated dogs that underwent TPLO had better outcomes than
      those that underwent LFS.

PMID- 23971848
TI  - Evaluation of short-term outcome after lung lobectomy for resection of primary
      lung tumors via video-assisted thoracoscopic surgery or open thoracotomy in
      medium- to large-breed dogs.
AB  - OBJECTIVE: To describe clinicopathologic features of dogs that underwent lung
      lobectomy for resection of primary lung tumors via video-assisted thoracoscopic
      surgery (VATS) or open thoracotomy (OT) and to compare short-term outcomes for
      dogs following these procedures. DESIGN: Retrospective cohort study. ANIMALS: 46
      medium- to large-breed dogs with primary lung tumors. PROCEDURES: Medical records
      of dogs that underwent a lung lobectomy via VATS (n = 22) or OT (24) for
      resection of primary lung tumors between 2004 and 2012 were reviewed. Dogs were
      included if they weighed > 10 kg (22 lb) and resection of a primary lung tumor
      was confirmed histologically. Tumor volumes were calculated from preoperative CT
      scans where available. Surgical time, completeness of excision, time in the ICU,
      indwelling thoracic drain time, postoperative and total hospitalization time,
      incidence of major complications, and short-term survival rate were evaluated.
      RESULTS: VATS was performed with a 3-port (n = 12) or 4-port (10) technique and 1
      lung ventilation (22). In 2 of 22 (9%) dogs, VATS was converted to OT. All dogs
      survived to discharge from the hospital. There were no significant differences
      between the VATS and OT groups with regard to most variables. Surgery time was
      significantly longer for VATS than for OT (median, 120 vs 95 minutes,
      respectively). CONCLUSIONS AND CLINICAL RELEVANCE: In medium- to large-breed
      dogs, short-term outcomes for dogs that underwent VATS for lung lobectomy were
      comparable to those of dogs that underwent OT. Further studies are required to
      evaluate the effects of surgical approach on indices of postoperative pain and
      long-term outcomes.

PMID- 23971849
TI  - Use of an owner questionnaire to evaluate long-term surgical outcome and chronic
      pain after cranial cruciate ligament repair in dogs: 253 cases (2004-2006).
AB  - OBJECTIVE: To evaluate, by means of an owner questionnaire, long-term outcome and
      prevalence of chronic pain after cranial cruciate ligament (CCL) surgery in dogs.
      DESIGN: Retrospective case series. ANIMALS: 253 dogs with surgically treated CCL
      rupture. PROCEDURES: Data from surgical records of dogs that underwent surgical
      repair of CCL between 2004 and 2006 were reviewed. An owner questionnaire,
      including the validated Helsinki chronic pain index (HCPI), served to evaluate
      long-term outcome and prevalence of chronic pain after surgical repair by means
      of intracapsular, extracapsular, or osteotomy techniques. Additional questions
      inquired about recovery and rehabilitation after surgery, current well-being,
      medications, and adjunct treatments. RESULTS: Of 507 questionnaires, 272 (53.6%)
      were returned; 19 were excluded because of incomplete answers. Mean +/- SD follow
      up time was 2.7 +/- 0.8 years (range, 1.3 to 4.5 years). Owners considered
      surgical outcome as excellent in 122 of 226 (54.0%) dogs, good in 97 (42.9%),
      fair in 0 (0%), and poor in 7 (3.1%). At follow-up, the mean +/- SD HCPI for 206
      dogs was 8.9 +/- 6.3 (range, 0 to 24). Of these 206 dogs, 64 (31.1%) had an HCPI
      >= 12, indicating chronic pain. Mean HCPI in dogs with a good outcome (11.8 +/-
      5.4; 95% confidence interval, 10.6 to 12.9) was significantly higher than that
      for dogs with an excellent outcome (6.2 +/- 5.7; 95% confidence interval, 5.1 to
      7.2). Owner-reported postoperative lameness was significantly shorter after
      osteotomy techniques, compared with lameness duration after the intracapsular
      technique. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of owner assessment,
      long-term chronic pain was found in approximately 30% of dogs after CCL repair.

PMID- 23971850
TI  - Risk factors associated with survival in dogs with nontonsillar oral squamous
      cell carcinoma 31 cases (1990-2010).
AB  - OBJECTIVE: To identify risk factors associated with survival in dogs with
      nontonsillar oral squamous cell carcinoma (OSCC) that were and were not treated
      with curative-intent surgery. DESIGN: Retrospective case series. ANIMALS: 31 dogs
      with OSCC. PROCEDURES: Medical records for dogs with OSCC that were not treated,
      or were treated with curative-intent surgery only between January 1990 and
      December 2010 were reviewed. For each dog, data regarding signalment, clinical
      stage, treatment, tumor recurrence, and survival time were obtained from the
      medical record, and archived biopsy specimens were evaluated to identify the
      histologic subtype of the tumor and extent of tumor-associated inflammation
      (TAI), perineural invasion (PNI), and lymphovascular invasion (LVI). RESULTS:
      Risk of death for the 21 dogs with OSCC that were surgically treated was
      decreased 91.4% (hazard ratio, 0.086; 95% confidence interval, 0.002 to 0.150),
      compared with that for the 10 dogs with OSCC that were not treated. The 1-year
      survival rate was 93.5% and 0% for dogs that were and were not surgically
      treated, respectively. Risk of death increased significantly with increasing TAI
      and increasing risk score (combination of TAI, PNI, and LVI). Tumor location,
      clinical stage, and histologic subtype were not associated with survival time.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the prognosis for dogs
      with OSCC was excellent following surgical excision of the tumor. Risk of death
      increased with increasing TAI, and combining TAI, PNI, and LVI into a single risk
      score may be a useful prognostic indicator for dogs with OSCC.

PMID- 23971851
TI  - Evaluation of costs and time required for laparoscopic-assisted versus open
      cystotomy for urinary cystolith removal in dogs: 43 cases (2009-2012).
AB  - OBJECTIVE: To compare required time and costs of surgery and hospitalization as
      well as prevalence of incomplete urinary cystolith removal associated with
      laparoscopic-assisted cystotomy versus open cystotomy in dogs. DESIGN:
      Retrospective case series. ANIMALS: 20 dogs with urolithiasis treated by
      laparoscopic-assisted cystotomy and 23 dogs treated by open cystotomy.
      PROCEDURES: Medical records were reviewed. Surgery cost, hospitalization cost,
      total cost, surgery time, days in hospital, incomplete cystolith removal, and
      number of doses of analgesic administered IV after surgery were compared between
      the laparoscopic-assisted cystotomy and open cystotomy groups. Results-Surgery
      cost and total cost were significantly higher in the laparoscopic-assisted
      cystotomy group. Hospitalization cost, days in hospital, and prevalence of
      incomplete cystolith removal did not differ significantly between groups. Number
      of doses of analgesic was significantly lower in the laparoscopic-assisted
      cystotomy group. CONCLUSIONS AND CLINICAL RELEVANCE: Laparoscopic-assisted
      cystotomy was more time-consuming and expensive but associated with fewer
      postoperative doses of injectable analgesics, compared with open cystotomy.
      Laparoscopic-assisted cystotomy is an acceptable, more expensive, and minimally
      invasive alternative to open cystotomy for the removal of urinary cystoliths in
      dogs.

PMID- 23971852
TI  - Suspected carprofen toxicosis caused by coprophagia in a dog.
AB  - CASE DESCRIPTION: A 1-year-old spayed female mixed-breed dog was evaluated
      because of urinary incontinence, polyuria, polydipsia, and minimally concentrated
      urine. CLINICAL FINDINGS: Markedly high circulating alanine transaminase
      activity, mildly high circulating alkaline phosphatase activity, and low urine
      specific gravity were detected for the dog. Results of ultrasonographic
      examination of the abdomen and cytologic examination of liver samples were
      unremarkable. Carprofen was detected in serum and plasma samples obtained from
      the dog. Exposure to carprofen was attributed to ingestion of feces of another
      dog in the household that was receiving the drug daily. TREATMENT AND OUTCOME:
      Access to feces of other dogs in the household was prevented; no other treatment
      was initiated. Urinary incontinence, polyuria, and polydipsia resolved, and urine
      specific gravity increased within 7 days following discontinuation of consumption
      of feces. Alanine transaminase activity was substantially lower than the value
      determined during the initial examination, and alkaline phosphatase activity was
      within the reference range 5 weeks after discontinuation of consumption of feces
      by the dog. CLINICAL RELEVANCE: Findings for the dog of this report suggested
      that carprofen toxicosis can be caused by consumption of feces of another dog
      receiving the drug. This cause of adverse effects should be a differential
      diagnosis for dogs with clinical signs and clinicopathologic abnormalities
      consistent with carprofen toxicosis.

PMID- 23971853
TI  - Substance Use Among Adolescents in California: A Latent Class Analysis.
AB  - Data from the California Healthy Kids Survey of 7th, 9th, and 11th graders were
      used to identify latent classes/clusters of alcohol, tobacco, and marijuana use
      (N = 418,702). Analyses revealed four latent classes of substance use, which
      included nonusers (61.1%), alcohol experimenters (some recent alcohol use;
      22.8%), mild polysubstance users (lifetime use of all substances with less than 3
      days of recent use; 9.2%), and frequent polysubstance users (used all substances
      three or more times in the past month; 6.9%). The results revealed that alcohol
      and marijuana use are salient to California adolescents. This information can be
      used to target and tailor school-based prevention efforts.

PMID- 23971854
TI  - The Department of Veterans Affairs Biorepository Brain Bank: a national resource
      for amyotrophic lateral sclerosis research.
AB  - Our objective was to describe a unique national resource to facilitate
      amyotrophic lateral sclerosis (ALS) research, the Department of Veterans Affairs
      Biorepository Brain Bank. Enrolled veterans receive biannual telephone follow-up
      to collect clinical data until death including the ALS Functional Rating Scale
      Revised (ALSFRS-R). A comprehensive post mortem examination is performed and a
      wide range of fixed and frozen brain and spinal cord samples are banked. As of
      December 2012, 240 veterans were enrolled from 47 states and post mortem tissue
      recoveries were performed on 100 veterans from 37 states. Average disease
      duration was 13.5 (range 3-45) years. Average follow-up for living subjects was
      3.1 years and average ALSFRS-R score was 23.5 compared to 25.9 (12-24 months
      earlier), indicating slow disease progression. ALS was confirmed by post mortem
      examination in 97% of cases. Eighty-six percent of cases were TDP-43-positive.
      Additional neuropathological diagnoses include Lewy body disease (13%),
      frontotemporal lobar degeneration (6.3%), chronic traumatic encephalopathy with
      motor neuron disease (3.2%), and Alzheimer's disease (2.1%). Tissue RIN values
      were >= 4.0 in 88% of cases. In conclusion, the availability of high quality
      fixed and frozen CNS tissue from this well characterized cohort is an important
      resource to facilitate research into genetic and environmental risk factors and
      clinical pathological relationships in ALS.

PMID- 23971855
TI  - Minilaparotomy cholecystectomy with ultrasonic dissection versus conventional
      laparoscopic cholecystectomy: a randomized multicenter study.
AB  - OBJECTIVE: Cholecystectomy by minilaparotomy (MC) or by laparoscopy (LC) has been
      shown to have equal results of both early and late recovery. Although, the
      ultrasonic dissection (UsD) technique has seen used in LC, the technique is
      rarely used in MC. MATERIAL AND METHODS: Initially, 88 patients with
      uncomplicated symptomatic gallstones were randomized into MC with UsD (n = 44) or
      conventional LC (n = 44) over a 2-year period (2010-2012). The two groups were
      similar in terms of age and American Society of Anesthesiologists (ASA) physical
      status score. Results. Both groups were similar in terms of the operative time
      and the time in the operation theatre, the success of day-surgery and
      satisfaction with the procedure. The MC group had significantly less
      postoperative pain than the LC group, p = 0.002, and the MC group used less
      analgesics doses during the first 24 h: 2.8 (1.2) doses vs. 3.8 (1.4) doses, p =
      0.003. The convalescence needed was 3 days shorter in the MC group, 7 (3) days,
      than that in the LC-group, 10 (8) days, p = 0.024. In the MC group 4 patients and
      in the LC group 11 (p = 0.046) required more than 14 days of sick leave. In the
      MC group there was one and in the LC group two conversions to open surgery.
      CONCLUSION: The patients in the MC group had less early postoperative pain and
      had a shorter convalescence than the patients in the LC group.

PMID- 23971856
TI  - Welcome to the 83rd Annual Meeting of the American Thyroid Association.

PMID- 23971857
TI  - An adolescent treated with rapid maxillary expansion presenting with strabismus:
      a case report.
AB  - INTRODUCTION: Few in vivo studies have investigated the effect of maxillary
      expansion on strabismus; however, some in vitro studies hypothesized that changes
      in the palatal width obtained with rapid maxillary expansion appliances could
      involve other bone structures that contain blood vessels and nerves conveying to
      the orbital cavity. The present case report seems to support that hypothesis,
      even if no analysis of pathogenetic mechanisms could be drawn. CASE PRESENTATION:
      We present the case of a 14-year-old Caucasian girl affected by strabismus and
      referred for the treatment of a class III malocclusion with transverse maxillary
      deficiency, which was corrected by the application of a rapid maxillary expansion
      appliance (Haas type). At 2 months follow-up, the patient, who had not undergone
      any ophthalmologic treatment, was submitted to an ophthalmologic examination that
      revealed a marked change in the vision defect, which slightly relapsed at 6
      months. CONCLUSIONS: The results of our clinical evaluation showed a remarkable
      modification of the oculomotor system of our patient as an outcome of the rapid
      maxillary expansion.Further studies are needed to clarify these findings and to
      investigate the clinical implications of these observations.

PMID- 23971859
TI  - Does self reflection and insight correlate with academic performance in medical
      students?
AB  - BACKGROUND: Medical students in academic difficulty are often described as
      lacking insight. The Self Reflection and Insight Scale (SRIS) is a tool for
      measuring insight which has been validated in medical students. We investigated
      whether self reflection and insight scores correlate with academic performance in
      Year 4 medical students from a six year undergraduate medical degree, and whether
      self reflection and insight changes after one year of clinical training. METHODS:
      Self reflection and insight scores were measured in 162 students at the start of
      Year 4 at the University of Western Australia. Performance in end of year written
      and clinical exams was monitored and correlated with SRIS. Seventy of the
      students were surveyed again at the start of Year 5 to see if scores changed or
      were stable after one year of full time clinical training. RESULTS: We found no
      correlation between self reflection or insight and academic performance in
      written and clinical exams. There was a significant increase in recognition of
      the need for self reflection in Year 5 compared with Year 4. CONCLUSIONS: While
      no correlation was found between this measure of self reflection and insight with
      academic performance, there was an increase in students' recognition of the need
      for reflection after one year of clinical studies. This study is a valuable first
      step towards a potentially exciting research domain and warrants further
      longitudinal evaluation with larger cohorts of students using additional measures
      of achievement.

PMID- 23971858
TI  - Composite versus conventional coronary artery bypass grafting strategy for the
      anterolateral territory: study protocol for a randomized controlled trial.
AB  - BACKGROUND: In severe coronary artery disease, coronary artery bypass grafting
      (CABG) surgery is indicated to re-establish an adequate blood supply to the
      ischemic myocardium. Effectiveness of CABG surgery for symptom relief and
      mortality decrease should therefore depend on bypass graft patency. As bypass
      using a left internal mammary artery (LIMA)-to-left anterior descending coronary
      artery (LAD) anastomosis allows the best results in terms of graft patency, we
      designed a new surgical technique using a saphenous vein graft as a venous bridge
      to distribute the LIMA flow to the cardiac anterolateral territory. This novel
      strategy could extend the patency benefits associated to the LIMA. Other
      potential benefits of this technique include easier surgical technique,
      possibility to use saphenous vein grafts as vein patch angioplasty, shorter
      saphenous vein grafts requirement and reduced or eliminated manipulations of the
      ascendant aorta (and associated stroke risk). METHODS/DESIGN: Between July 2012
      and 2016, 200 patients undergoing a primary isolated CABG surgery using
      cardiopulmonary bypass with a LAD bypass graft and at least another target on the
      anterolateral territory will be randomized (1:1) according to 1) the new
      composite strategy and 2) the conventional strategy with a LIMA-to-LAD
      anastomosis and revascularization of the other anterolateral target(s) with a
      separated aorto-coronary saphenous vein graft. The primary objective of the trial
      is to assess whether the composite strategy allows non-inferior anterolateral
      graft patency index (proportion of non-occluded CABGs out of the total number of
      CABGs) compared to the conventional technique. The primary outcome is the
      anterolateral graft patency index, evaluated at one year by 256-slice computed
      tomography angiography. Ten years of clinical follow-up is planned to assess
      clinical outcomes including death, myocardial infarction and need for
      revascularization. DISCUSSION: This non-inferiority trial has the potential to
      advance the adult cardiac surgery field, given the potential benefits associated
      with the composite grafting strategy. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01585285.

PMID- 23971860
TI  - Development of hairy cell leukemia in familial platelet disorder with
      predisposition to acute myeloid leukemia.
AB  - Abstract Familial platelet disorder with predisposition to acute myeloid leukemia
      (FPD/AML) is an autosomal dominant disorder characterized by mild to moderate
      thrombocytopenia with or without its impaired function, inherited RUNX1 mutation
      and high incidence of myeloid malignancy, such as myelodysplastic syndrome or
      acute myeloid leukemia. A 72-year-old male visited our institute because of
      gradually progressive pancytopenia and splenomegaly, and was diagnosed as having
      hairy cell leukemia. He was administered one course of intravenous cladribine
      (0.12 mg/kg, day 1-5) and achieved hematological complete response. Mutation
      analyses of RUNX1 gene were underwent because familial history of hematological
      malignancies evoked a possibility of FPD/AML. As a result, RUNX1 L445P mutation
      was identified in the peripheral blood and the mutation was considered as germ
      line mutation because the same mutation was detected in the buccal mucosa. BRAF
      V600E mutation was also identified in the peripheral blood but not in the buccal
      mucosa. To our knowledge, this is the first report of B cell malignancy arising
      from FPD/AML.

PMID- 23971861
TI  - Functionalized ultrasound-propelled magnetically guided nanomotors: toward
      practical biomedical applications.
AB  - Magnetically guided ultrasound-powered nanowire motors, functionalized with
      bioreceptors and a drug-loaded polymeric segment, are described for "capture and
      transport" and drug-delivery processes. These high-performance fuel-free motors
      display advanced capabilities and functionalities, including magnetic guidance,
      coordinated aligned movement, cargo towing, capture and isolation of biological
      targets, drug delivery, and operation in real-life biological and environmental
      media. The template-prepared three-segment Au-Ni-Au nanowire motors are propelled
      acoustically by mechanical waves produced by a piezoelectric transducer. An
      embedded nickel segment facilitates a magnetically guided motion as well as
      transport of large "cargo" along predetermined trajectories. Substantial
      improvement in the speed and power is realized by the controlled concavity
      formation at the end of the motor nanowire using a sphere lithography protocol.
      Functionalization of the Au segments with lectin and antiprotein A antibody
      bioreceptors allows capture and transport of E. coli and S. aureus bacteria,
      respectively. Potential therapeutic applications are illustrated in connection to
      the addition of a pH-sensitive drug-loaded polymeric (PPy-PSS) segment. The
      attractive capabilities of these fuel-free acoustically driven functionalized Au
      Ni-Au nanowires, along with the simple preparation procedure and minimal adverse
      effects of ultrasonic waves, make them highly attractive for diverse in vivo
      biomedical applications. 

PMID- 23971862
TI  - Improving nursing home care for dementia: is the environment the answer?

PMID- 23971863
TI  - Expression of SAP5 and SAP9 in Candida albicans biofilms: comparison of
      bloodstream isolates with isolates from other sources.
AB  - Secreted aspartic proteases (Sap), encoded by a family of 10 SAP genes, are key
      virulence determinants in Candida albicans. Although biofilm-associated
      bloodstream infections (BSIs) are frequently caused by C. albicans, SAP gene
      expression in C. albicans biofilms formed by BSI isolates has not been evaluated.
      We compared the expression of two SAP genes, SAP5 and SAP9, in C. albicans
      biofilms formed by BSI isolates with those formed by isolates from other body
      sites. Sixty-three C. albicans isolates were analyzed, comprising 35 BSI isolates
      and 28 from other sites. A denture-strip biofilm model was used, and expression
      of the two SAP genes was quantified by real-time RT-PCR during planktonic or
      biofilm growth. Mean SAP5 expression levels of the BSI isolates were 3.59-fold
      and 3.86-fold higher in 24-h and 48-h biofilms, respectively, than in planktonic
      cells. These results did not differ from those for isolates from other sites
      (2.71-fold and 2.8-fold for 24-h and 48-h biofilms, respectively). By contrast,
      mean SAP9 expression during biofilm formation was higher in BSI isolates (2.89
      fold and 3.29-fold at 24 and 48 h, respectively) than in isolates from other
      sites (1.27-fold and 1.32-fold at 24 and 48 h, respectively; both, P < 0.001).
      These results show, for the first time, that both SAP5 and SAP9 are upregulated
      in C. albicans biofilms formed by BSI isolates, and that BSI isolates may have a
      greater capacity to express SAP9 under biofilm conditions than isolates from
      other sites.

PMID- 23971864
TI  - Phenotypic switching in Candida tropicalis: association with modification of
      putative virulence attributes and antifungal drug sensitivity.
AB  - Although Candida tropicalis has become an increasingly important human pathogen,
      little is known regarding its potential to cause disease. In this study we
      evaluated the phenotypic switching ability of C. tropicalis and analyzed the
      effect of switching on biological properties related to virulence factors. We
      demonstrated that C. tropicalis switched spontaneously, reversibly and at high
      frequency (10(-1) to 10(-3)) when grown on yeast extract-peptone-D-glucose (YPD)
      agar medium. Phenotypic switching in five clinical isolates of C. tropicalis
      resulted in colonies exhibiting the following morphologies: crepe, rough, crater,
      irregular center, mycelial and diffuse. The majority of the variant colonies were
      associated with higher percentages of filamentous growth relative to their
      parental unswitched isolates. Significant differences (P < 0.05) in the
      production of hemolytic factor were found between most of the switched variants
      and their respective parental counterparts. Variant colonies exhibiting the crepe
      (derived from isolates 49.07 and 100.10) and rough phenotype (derived from
      isolate 49.07) had higher biofilm formation than their parental counterparts
      exhibiting a smooth dome surface (P < 0.05). Our data revealed that switching was
      correlated with changes in the in vitro minimum inhibitory concentrations (MICs)
      of a subset of the switched variants phenotypes to itraconazole. While the MIC to
      itraconazole was higher for crepe variant compared with its parental isolate
      49.07, the rough variant of 100.10 had a lower MIC to this antifungal agent. The
      presented data support the role of phenotypic switching in promoting changes in
      phenotypic expression of putative virulence traits and itraconazole
      susceptibility of clinical isolates of C. tropicalis. 

PMID- 23971865
TI  - Characterization of binding interactions of (-)-epigallocatechin-3-gallate from
      green tea and lipase.
AB  - Understanding the interaction of (-)-epigallocatechin-3-gallate (EGCG) and lipase
      is important for understanding EGCG's inhibition of lipase. In this paper, the
      interaction of EGCG and porcine lipase was characterized by fluorescence
      spectroscopy, circular dichroism (CD), isothermal titration calorimetry, and
      molecular docking. EGCG might act as a noncompetitive pancreatic lipase
      inhibiter. EGCG bound to lipase with affinity of K(a) = 2.70 * 104 L mol-1.
      Thermodynamic features suggested that the interaction process was spontaneous,
      with hydrogen bonds and electrostatic force perhaps primarily responsible for the
      interaction, with 1:1 interaction of lipase and EGCG. CD studies indicated
      conformation change of lipase on binding to EGCG. Furthermore, docking results
      supported experimental findings and revealed hydrogen-bonding interaction with
      Val21, Glu188, and Glu220. This noncovalent bonding between EGCG and lipase
      alters the molecular conformation of lipase, which decreases the enzyme catalytic
      activity. This study will help further understand the antiobesity mechanisms of
      green tea.

PMID- 23971866
TI  - Synthesis of a rotaxane Cu(I) triazolide under aqueous conditions.
AB  - We describe the serendipitous isolation of a stable, neutral, monomeric
      mechanically interlocked Cu(I) triazolide under aqueous conditions. This
      "trapped" intermediate of the CuAAC catalytic cycle is sterically protected from
      reprotonation by the rotaxane architecture, which renders the Cu(I)-C bond stable
      toward moisture and air--even carboxylic acids protonate the Cu(I)-C bond only
      slowly. The isolation of this remarkably stable Cu(I) organometallic points
      toward potential applications of mechanical bonding in the study of reactive
      intermediates.

PMID- 23971867
TI  - Imaging fluorescent nanoparticles to probe photoinduced charging of a
      semiconductor-solution interface.
AB  - Optically transparent semiconductors allow simultaneous control of interfacial
      electrical potential and spectroscopic observation of chemistry near the
      electrode surface. Care must be taken, however, to avoid unwanted photoexcitation
      induced charging of the semiconductor electrode that could influence the results.
      In this work, we investigate the in situ surface charging by photoexcitation well
      below the band gap of an optically transparent semiconductor, indium-tin oxide
      (ITO) electrode. Using total-internal-reflection fluorescence microscopy, the
      population of ~100-nm negatively charged carboxylate-polystyrene fluorescent
      nanoparticles at an ITO-aqueous solution interface could be monitored in situ. At
      positive applied potentials (~0.7 V versus Ag/AgCl), nanoparticles accumulate
      reversibly in the electrical double-layer of the ITO surface, and the interfacial
      nanoparticle populations increase with 488-nm excitation intensity. The potential
      sensitivity of nanoparticle population exhibited no dependence on excitation
      intensity, varied from 0.1 to 10 W cm(-2), while the onset potential for particle
      accumulation shifted by as much as 0.3 V. This shift in surface potential appears
      to be due to photoexcitation-induced charging of the ITO, even though the
      excitation radiation photon energy, ~2.4 eV, is well below the primary band gap
      of ITO, >3.5 eV. A kinetic model was developed to determine the photon order of
      electron-hole generation relative to the electron-hole recombination. The
      photoexcitation process was found to be first-order in photon flux, suggesting
      one-photon excitation of an indirect band gap or defect sites, rather than two
      photon excitation into the direct band gap. A control experiment was conducted
      with red-fluorescent carboxylate-polystyrene particles that were counted using
      647-nm excitation, where the photon energy is below the indirect band gap or
      defect site energy and where the optical absorption of the film vanishes. Red
      illumination between 1 and 15 W cm(-2) produced no detectable shifts in the onset
      accumulation potential, which is consistent with the negligible optical
      absorption of the ITO film at this longer wavelength.

PMID- 23971868
TI  - Regioselective sulfonylation and N- to O-sulfonyl migration of quinazolin-4(3H)
      ones and analogous thienopyrimidin-4(3H)-ones.
AB  - The sulfonylation of quinazolin-4(3H)-ones and related tetrahydrobenzothieno[2,3
      d]pyrimidin-4(3H)-ones with mesyl, tosyl, and p-cyanobenzenesulfonyl chloride was
      studied. A hydrogen substituent at 2-position directed the sulfonyl group to the
      N-3 position, while alkylsulfanyl or amino substituents led to sulfonylation of
      the carbonyl oxygen. The latter effect was attributed to steric influence and the
      positive mesomeric effect of the 2-substituent. An access to N-sulfonylated 2
      substituted regioisomers was established. An unexpected 1,3-sulfonyl migration
      was observed and further analyzed. This process occurred as an intramolecular N-
      to O-shift as verified by kinetic and crossover experiments. 

PMID- 23971869
TI  - The need for safer medication use in pregnancy.

PMID- 23971870
TI  - Once-daily glycopyrronium via the Breezhaler(r) device for the treatment of COPD:
      pharmacological and clinical profile.
AB  - In the management of chronic obstructive pulmonary disease (COPD), there is an
      unmet medical need for effective bronchodilator treatments that not only have a
      fast onset of action, but also a long duration of action and are delivered using
      a simple, easy-to-use device. Long-acting muscarinic antagonists such as
      glycopyrronium and tiotropium, along with long-acting beta-2 agonists such as
      indacaterol, formoterol and salmeterol are the pillars of pharmacological therapy
      for the long-term management of patients with COPD. Glycopyrronium, the
      quaternary ammonium ion of glycopyrronium bromide, acts as a competitive
      antagonist by selectively binding to the muscarinic receptors in the bronchial
      smooth musculature, thus inhibiting acetylcholine-mediated bronchoconstriction.
      Glycopyrronium is an inhaled once-daily long-acting muscarinic antagonist
      recently approved for the maintenance treatment of patients with COPD.
      Glycopyrronium is administered by a single-dose, dry-powder inhaler, the
      Breezhaler(r) device, designed specifically to have a low internal resistance, be
      easy to use and confirm efficient drug delivery in patients with a wide range of
      COPD severities, irrespective of the age. Glycopyrronium has been shown to
      provide rapid and sustained improvements in lung function, dyspnea, health
      status, exercise endurance and exacerbation risk and an acceptable safety and
      tolerability profile. 

PMID- 23971871
TI  - Davunetide: a review of safety and efficacy data with a focus on
      neurodegenerative diseases.
AB  - Davunetide is the first neuroprotective peptide in its class, and has preclinical
      evidence for neuroprotective, neurotrophic and cognitive protective properties.
      Davunetide has also been shown to prevent apoptosis or programmed-cell death in a
      range of in vitro and in vivo models by promoting microtubule stabilization.
      Potential clinical uses of davunetide include neurodegenerative disorders such as
      Alzheimer's disease (AD), progressive supranuclear palsy (PSP), frontotemporal
      dementia (FTD) or cognitive impairment in other diseases such as schizophrenia
      where microtubule structure and function is known to be impaired. The nonclinical
      and clinical safety of davunetide is reviewed here in detail. Pre-clinical
      toxicology studies in rats and dogs using the maximum feasible dose of davunetide
      provide strong evidence that davunetide is well-tolerated. Similarly, data from
      10 separate clinical trials of davunetide, investigating safety and efficacy
      provide evidence that davunetide is generally safe and well-tolerated, and has
      shown some signs of clinical efficacy. 

PMID- 23971872
TI  - European Union Clinical Trials Register: on the way to more transparency of
      clinical trial data.

PMID- 23971874
TI  - Update on current and future novel therapies for dry age-related macular
      degeneration.
AB  - Age-related macular degeneration (ARMD) is the leading cause of irreversible
      blindness in developed countries. There are currently no cures, but there are
      promising potential therapies that target the underlying disease mechanisms of
      dry ARMD. Stem cells, ciliary neurotrophic factor, rheopheresis, ozonated
      autohemotherapy and prostaglandins show promise in stabilizing or improving
      visual acuity. Age-Related Eye Disease Study vitamins may reduce progression to
      severe ARMD. Adjuvant therapy like low vision rehabilitation and implantable
      miniature telescopes may help patients adjust to the sequelae of their disease,
      and herbal supplementation with saffron, zinc monocysteine and phototrop may be
      helpful. Therapies that are currently in clinical trials include brimonidine,
      doxycycline, anti-amyloid antibodies (GSK933776 and RN6G), RPE65 inhibitor (ACU
      4429), complement inhibitors (ARC1905, FCFD4514S), hydroxychloroquine,
      intravitreal fluocinolone acetate and vasodilators like sildenafil, moxaverine
      and MC-1101. Therapies that have not been shown to be effective include POT-4,
      eculizumab, tandospirone, anecortave acetate, the antioxidant OT-551, sirolimus
      and vitamin E. 

PMID- 23971873
TI  - Translating colorectal cancer prevention through the guanylyl cyclase C signaling
      axis.
AB  - Colorectal cancer (CRC) is a major public health concern, ranking among the
      leading causes of cancer death in both men and women. Because of this continued
      burden there is a clear need for improved treatment, and more importantly
      prevention of this disease. In recent years there is significant evidence to
      support the hypothesis that guanylyl cyclase C (GCY2C) is a tumor suppressor in
      the intestine, and that the loss of hormone ligands for this receptor is an
      important step in the disease process. Thus, ligand replacement therapy has been
      proposed as a strategy to prevent CRC. Until recently this strategy was not
      clinically plausible; however, the recent regulatory approval of linaclotide
      (LINZESSTM, Forest Laboratories and Ironwood Pharmaceuticals, Inc.), an oral
      GUCY2C ligand, has raised the possibility of utilizing this strategy clinically
      to prevent CRC.

PMID- 23971875
TI  - Alcohol brand references in U.S. popular music, 2009-2011.
AB  - This study aimed to assess the prevalence and context of alcohol brand references
      in popular music. Billboard Magazine year-end charts from 2009 to 2011 were used
      to identify the most popular songs in four genres: Urban, Pop, Country, and Rock.
      Of the 720 songs, 23% included an alcohol mention, and 6.4% included an alcohol
      brand mention. Songs classified as Urban had the highest percentage of alcohol
      mentions and alcohol brand mentions. The context associated with alcohol brand
      mentions was almost uniformly positive or neutral. Public health efforts may be
      necessary to reduce youth exposure to these positive messages about alcohol use. 

PMID- 23971876
TI  - Multiwell CO2 injectivity: impact of boundary conditions and brine extraction on
      geologic CO2 storage efficiency and pressure buildup.
AB  - CO2 storage efficiency is a metric that expresses the portion of the pore space
      of a subsurface geologic formation that is available to store CO2. Estimates of
      storage efficiency for large-scale geologic CO2 storage depend on a variety of
      factors including geologic properties and operational design. These factors
      govern estimates on CO2 storage resources, the longevity of storage sites, and
      potential pressure buildup in storage reservoirs. This study employs numerical
      modeling to quantify CO2 injection well numbers, well spacing, and storage
      efficiency as a function of geologic formation properties, open-versus-closed
      boundary conditions, and injection with or without brine extraction. The set of
      modeling runs is important as it allows the comparison of controlling factors on
      CO2 storage efficiency. Brine extraction in closed domains can result in storage
      efficiencies that are similar to those of injection in open-boundary domains.
      Geomechanical constraints on downhole pressure at both injection and extraction
      wells lower CO2 storage efficiency as compared to the idealized scenario in which
      the same volumes of CO2 and brine are injected and extracted, respectively.
      Geomechanical constraints should be taken into account to avoid potential damage
      to the storage site. 

PMID- 23971877
TI  - De novo transcriptomic analysis of hydrogen production in the green alga
      Chlamydomonas moewusii through RNA-Seq.
AB  - BACKGROUND: Microalgae can make a significant contribution towards meeting global
      renewable energy needs in both carbon-based and hydrogen (H2) biofuel. The
      development of energy-related products from algae could be accelerated with
      improvements in systems biology tools, and recent advances in sequencing
      technology provide a platform for enhanced transcriptomic analyses. However,
      these techniques are still heavily reliant upon available genomic sequence data.
      Chlamydomonas moewusii is a unicellular green alga capable of evolving molecular
      H2 under both dark and light anaerobic conditions, and has high hydrogenase
      activity that can be rapidly induced. However, to date, there is no systematic
      investigation of transcriptomic profiling during induction of H2 photoproduction
      in this organism. RESULTS: In this work, RNA-Seq was applied to investigate
      transcriptomic profiles during the dark anaerobic induction of H2
      photoproduction. 156 million reads generated from 7 samples were then used for de
      novo assembly after data trimming. BlastX results against NCBI database and
      Blast2GO results were used to interpret the functions of the assembled 34,136
      contigs, which were then used as the reference contigs for RNA-Seq analysis. Our
      results indicated that more contigs were differentially expressed during the
      period of early and higher H2 photoproduction, and fewer contigs were
      differentially expressed when H2-photoproduction rates decreased. In addition, C.
      moewusii and C. reinhardtii share core functional pathways, and transcripts for
      H2 photoproduction and anaerobic metabolite production were identified in both
      organisms. C. moewusii also possesses similar metabolic flexibility as C.
      reinhardtii, and the difference between C. moewusii and C. reinhardtii on
      hydrogenase expression and anaerobic fermentative pathways involved in redox
      balancing may explain their different profiles of hydrogenase activity and
      secreted anaerobic metabolites. CONCLUSIONS: Herein, we have described a workflow
      using commercial software to analyze RNA-Seq data without reference genome
      sequence information, which can be applied to other unsequenced microorganisms.
      This study provided biological insights into the anaerobic fermentation and H2
      photoproduction of C. moewusii, and the first transcriptomic RNA-Seq dataset of
      C. moewusii generated in this study also offer baseline data for further
      investigation (e.g. regulatory proteins related to fermentative pathway discussed
      in this study) of this organism as a H2-photoproduction strain.

PMID- 23971879
TI  - Writing letters to patients as an educational tool for medical students.
AB  - BACKGROUND: Despite rapid growth and development of medical technology, personal
      relationship between the patient and physician remains the basis of high quality
      treatment. The aim of our study was to develop, implement and evaluate patient
      therapeutic letters written by students as a tool in teaching family medicine.
      METHODS: The study included all 6th year students attending their rounds in
      family medicine, structured into two 10-day cycles, one in urban offices and one
      in offices on the Adriatic islands (rural). After receiving detailed
      instructions, students wrote letters to two patients after a consultation in the
      office. The letters were audited by patients and 3 family medicine experts who
      used a grading instrument (scale 0 - poor, 1 - medium, 2 - good) for 1) adequacy
      and clarity of description of patients' disease/state, 2) knowledge, 3) adequacy
      of recommendations, 4) courtesy and respect and 5) language and style. Patients
      and experts were also asked to underline phrases they thought would be difficult
      to understand; the underlined text was subjected to content analysis. RESULTS:
      Both the patients and the experts gave high scores for the value and quality of
      the letters in terms of the description of the problem, adequacy of
      recommendations given, and courtesy and respect (mean (+/-standard deviation)
      5.65 +/- 0.79 for patients vs. 4.87 +/- 0.79 for experts out of maximum score of
      6). Family medicine experts were stricter than patients in their evaluation of
      the content of the letters (adequacy and clarity of disease description (P <
      0.001) and adequacy of recommendations (P < 0.001). Both the patients and the
      experts seemed to like longer letters as the length of the letter showed
      significant positive correlation with the quality summary score (correlation r =
      0.492 vs. r = 0.338, respectively, P < 0.010). Overlapping of the text underlined
      as difficult to understand by patients and experts was found in 10 (11.6%) out of
      86 letters. The highest overlap (20 terms) was found for the category "Technical
      terms unclear to a lay reader". CONCLUSIONS: Writing of a letter to their first
      patients may be a useful tool for students to personally experience the practice
      of medicine and establish better partnership with patients in health care.

PMID- 23971880
TI  - Determinants of severity of menopausal symptoms among Saudi women in Riyadh city.
AB  - OBJECTIVE: To determine the relationship between sociodemographic, reproductive
      and lifestyle factors and the severity of menopausal symptoms among Saudi women
      attending a university hospital in Riyadh city. METHODS: A cross-sectional survey
      was carried out during 2010 in Riyadh city. Women aged > 40 years attending or
      accompanying their relatives in outpatient clinics in King Khalid University
      Hospital were invited to participate in the study. The English version of the
      Menopause Rating Scale (MRS) was used to assess the severity of menopausal
      symptoms after translation and validation on a sample of 30 women. RESULTS: A
      total of 490 women were included. Severe urogenital symptoms were more common
      among housewives compared to working women (odds ratio (OR) 2.27, 95% confidence
      interval (CI) 1.12-4.68) and women living in apartments or small houses compared
      to women living in villas (OR 1.70, 95% CI 1.90-2.64). Nulliparous women had more
      severe somatic symptoms compared to those who had been pregnant (OR 2.83, 95% CI
      1.10-7.69). Women who exercised regularly were less likely to experience severe
      somatic and urogenital symptoms (OR 0.57, 95% CI 0.37-0.86; OR 0.65, 95% CI 0.44
      0.98, respectively). Obese women experienced more severe psychosomatic symptoms
      compared to those of normal body mass index (OR 2.01, 95% CI 0.96-4.93).
      CONCLUSION: Women who are housewives, living in apartments, not exercising
      regularly and obese are more likely to suffer from severe symptoms of menopause.

PMID- 23971878
TI  - LOXL2 induces aberrant acinar morphogenesis via ErbB2 signaling.
AB  - INTRODUCTION: Lysyl oxidase-like 2 (LOXL2) is a matrix-remodeling enzyme that has
      been shown to play a key role in invasion and metastasis of breast carcinoma
      cells. However, very little is known about its role in normal tissue homeostasis.
      Here, we investigated the effects of LOXL2 expression in normal mammary
      epithelial cells to gain insight into how LOXL2 mediates cancer progression.
      METHODS: LOXL2 was expressed in MCF10A normal human mammary epithelial cells. The
      3D acinar morphogenesis of these cells was assessed, as well as the ability of
      the cells to form branching structures on extracellular matrix (ECM)-coated
      surfaces. Transwell-invasion assays were used to assess the invasive properties
      of the cells. Clinically relevant inhibitors of ErbB2, lapatinib and Herceptin
      (traztuzumab), were used to investigate the role of ErbB2 signaling in this
      model. A retrospective study on a previously published breast cancer patient
      dataset was carried out by using Disease Specific Genomic Analysis (DSGA) to
      investigate the correlation of LOXL2 mRNA expression level with metastasis and
      survival of ErbB2-positive breast cancer patients. RESULTS: Fluorescence staining
      of the acini revealed increased proliferation, decreased apoptosis, and disrupted
      polarity, leading to abnormal lumen formation in response to LOXL2 expression in
      MCF10A cells. When plated onto ECM, the LOXL2-expressing cells formed branching
      structures and displayed increased invasion. We noted that LOXL2 induced ErbB2
      activation through reactive oxygen species (ROS) production, and ErbB2 inhibition
      by using Herceptin or lapatinib abrogated the effects of LOXL2 on MCF10A cells.
      Finally, we found LOXL2 expression to be correlated with decreased overall
      survival and metastasis-free survival in breast cancer patients with ErbB2
      positive tumors. CONCLUSIONS: These findings suggest that LOXL2 expression in
      normal epithelial cells can induce abnormal changes that resemble oncogenic
      transformation and cancer progression, and that these effects are driven by LOXL2
      mediated activation of ErbB2. LOXL2 may also be a beneficial marker for breast
      cancer patients that could benefit most from anti-ErbB2 therapy.

PMID- 23971881
TI  - Relationship between platelet indices and international normalized ratio in
      patients with non-valvular atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia and associated
      with adverse outcomes and increased risk for thromboembolic events. Warfarin is
      still the most extensively prescribed oral anticoagulant in AF to prevent
      ischemic complications. We aimed to determine the differences at platelet indices
      with warfarin usage layered by International Normalized Ratio (INR). A total of
      250 patients with permanent non-valvular AF (mean age 70.2 +/- 9.1; 153 female)
      were divided into two groups. Group 1 included 125 patients whose INR is between
      2.0 and 3.0 (called as "effective") and Group 2 included 125 patients whose INR
      is <2.0 (called as "ineffective"). Also 123 age- and sex-matched individuals in
      sinus rhythm enrolled as control group (Group 3). After physical and
      echocardiographic examination, complete blood counts and INR were studied. There
      was no statistically significant difference in age, sex, co-morbidities and
      medications, also hemoglobin, white blood cell and platelet counts among the
      groups. The CHA2DS2-VASc scores were similar between Groups 1 and 2. The mean
      platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT)
      were significantly higher in Group 2 than Groups 1 and 3 and similar between
      Groups 1 and 3. MPV was positively correlated with PDW and PCT and also inversely
      correlated with INR value and platelet count. On multivariate logistic regression
      analysis, MPV, PDW and PCT were independent predictors of ineffectiveness of INR.
      The results of this study showed that MPV, PDW and PCT are increased in patients
      with non-valvular AF without effective warfarin treatment. Warfarin usage
      adjusted by INR is associated with lower values of these platelet indices, even
      lower as the values of subjects in sinus rhythm. MPV, PDW and PCT are independent
      predictors of INR ineffectiveness and seem to be useful parameters for monitoring
      the effectiveness of warfarin treatment.

PMID- 23971882
TI  - Faecalibacterium prausnitzii supernatant improves intestinal barrier function in
      mice DSS colitis.
AB  - OBJECTIVE. The intestinal microbiota plays a substantial role in the pathogenesis
      of inflammatory bowel disease (IBD). Faecalibacterium prausnitzii (FP) is
      underrepresented in IBD patients and have been suggested to have anti
      inflammatory effects in mice. Increased intestinal permeability is common in IBD
      but the relationship between FP and intestinal barrier function has not been
      investigated. Our aim was to study treatment with FP supernatant on intestinal
      barrier function in a dextran sodium sulfate (DSS) colitis mice model. MATERIAL
      AND METHODS. C57BL/6 mice received 3% DSS in tap water ad libitum during five
      days to induce colitis. From day 3 the mice received a daily gavage with FP
      supernatant or broth during seven days. Ileum and colon were mounted in Ussing
      chambers for permeability studies with (51)Cr-EDTA and Escherichia coli K-12.
      Colon was saved for Western blot analyses of tight junction proteins. RESULTS.
      DSS-treated mice showed significant weight loss and colon shortening. Gavage with
      FP supernatant resulted in a quicker recovery after DSS treatment and less
      extensive colonic shortening. Ileal mucosa of DSS mice showed a significant
      increase in (51)Cr-EDTA-passage compared to controls. (51)Cr-EDTA passage was
      significantly decreased in mice receiving FP supernatant. No significant
      differences were observed in passage of E. coli K12. Western blots showed a trend
      to increased claudin-1 and claudin-2 expressions in DSS mice. CONCLUSIONS.
      Supernatant of FP enhances the intestinal barrier function by affecting
      paracellular permeability, and may thereby attenuate the severity of DSS-induced
      colitis in mice. These findings suggest a potential role of FP in the treatment
      of IBD.

PMID- 23971883
TI  - Decontamination of a hospital room using gaseous chlorine dioxide: Bacillus
      anthracis, Francisella tularensis, and Yersinia pestis.
AB  - This study assessed the efficacy of gaseous chlorine dioxide for inactivation of
      Bacillus anthracis, Francisella tularensis, and Yersinia pestis in a hospital
      patient care suite. Spore and vegetative cells of Bacillus anthracis Sterne 34F2,
      spores of Bacillus atrophaeus ATCC 9372 and vegetative cells of both Francisella
      tularensis ATCC 6223 and Yersinia pestis A1122 were exposed to gaseous chlorine
      dioxide in a patient care suite. Organism inactivation was then assessed by log
      reduction in viable organisms postexposure to chlorine dioxide gas compared to
      non-exposed control organism. Hospital room decontamination protocols utilizing
      chlorine dioxide gas concentrations of 377 to 385 ppm maintained to exposures of
      767 ppm-hours with 65% relative humidity consistently achieved complete
      inactivation of B. anthracis and B. atrophaeus spores, as well as vegetative
      cells of B. anthracis, F. tularensis, and Y. pestis. Decrease in exposure (ppm
      hours) and relative humidity (<65%) or restricting airflow reduced inactivation
      but achieved >8 log reductions in organisms. Up to 10-log reductions were
      achieved in a hospital room with limited impact on adjacent areas, indicating
      chlorine dioxide concentrations needed for decontamination of highly concentrated
      (>6 logs) organisms can be achieved throughout a hospital room. This study
      translates laboratory chlorine dioxide fumigation studies applied in a complex
      clinical environment. 

PMID- 23971885
TI  - Daily expression of six clock genes in central and peripheral tissues of a night
      migratory songbird: evidence for tissue-specific circadian timing.
AB  - In birds, independent circadian clocks reside in the retina, pineal, and
      hypothalamus, which interact with each other and produce circadian time at the
      functional level. However, less is known of the molecular clockwork, and of the
      integration between central and peripheral clocks in birds. The present study
      investigated this, by monitoring the timed expression of five core clock genes
      (Per2. Cry1. Cry2. Bmal1, and Clock) and one clock-controlled gene (E4bp4) in a
      night-migratory songbird, the redheaded bunting (rb; Emberiza bruniceps). The
      authors first partially cloned these six genes, and then measured their 24-h
      profiles in central (retina, hypothalamus) and peripheral (liver, heart, stomach,
      gut, testes) tissues, collected at six times (zeitgeber time 2 [ZT2], ZT6, ZT11,
      ZT13, ZT18, and ZT23; ZT0 = lights on) from birds (n = 5 per ZT) on 12 h:12 h
      light-dark cycle. rbPer2. rbCry1. rbBmal1, and rbClock were expressed with a
      significant rhythm in all the tissues, except in the retina (only rbClock) and
      testes. rbCry2, however, had tissue-specific expression pattern: a significant
      rhythm in the hypothalamus, heart, and gut, but not in the retina, liver,
      stomach, and testes. rbE4bp4 had a significant mRNA rhythm in all the tissues,
      except retina. Further, rbPer2 mRNA peak was phase aligned with lights on,
      whereas rbCry1. rbBmal1, and rbE4bp4 mRNA peaks were phase aligned with lights
      off. rbCry2 and rbClock had tissue-specific scattered peaks. For example, both
      rbCry2 and rbClock peaks were close to rbCry1 and rbBmal1 peaks, respectively, in
      the hypothalamus, but not in other tissues. The results are consistent with the
      autoregulatory circadian feedback loop, and indicate a conserved tissue-level
      circadian time generation in buntings. Variable phase relationships between gene
      pairs forming positive and negative limbs of the feedback loop may suggest the
      tissue-specific contribution of individual core circadian genes in the circadian
      time generation.

PMID- 23971886
TI  - Identification and analysis of binding site residues in protein-carbohydrate
      complexes using energy based approach.
AB  - Protein-carbohydrate interactions play important roles in several biological
      processes in living organisms. Understanding the recognition mechanism of protein
      carbohydrate complexes is a challenging task in molecular and computational
      biology. In this work, we have developed an energy based approach for identifying
      the binding sites and important residues for binding in protein-carbohydrate
      complexes. Our method identified 3.3% of residues as binding sites in protein-
      carbohydrate complexes whereas the binding site residues in protein-protein,
      protein-RNA and protein-DNA complexes are 10.8%, 7.6% and 8.7%, respectively. In
      all these complexes, binding site residues are accommodated in singleresidue
      segments so that the neighboring residues are not involved in binding. Binding
      propensity analysis indicates the dominance of Trp to interact with carbohydrates
      through aromatic-aromatic interactions. Further, the preference of residue pairs
      and tripeptides interacting with carbohydrates has been delineated. The
      information gained in the present study will be beneficial for understanding the
      recognition mechanism of protein-carbohydrate complexes and for predicting the
      binding sites in carbohydrate binding proteins. 

PMID- 23971884
TI  - ALSUntangled No. 22: Propofol.

PMID- 23971887
TI  - Paratesticular dedifferentiated liposarcoma with leiomyosarcomatous
      differentiation: a case report with a review of literature.
AB  - Paratesticular liposarcoma is a rare neoplasm, described in single case studies
      or components of larger studies, as histologically well-differentiated
      liposarcoma (WDL) and dedifferentiated liposarcoma (DL). However,
      leiomyosarcomatous differentiation is an extremely rare occurrence in WDL and DL.
      We report a case of leiomyosarcomatous differentiation in a 77-year-old man. The
      patient presented with a painless right scrotal mass. Magnetic resonance imaging
      showed a large mass along the right spermatic cord. The resected mass, measuring
      17.5 * 12 * 5 cm, was composed of a high-grade pleomorphic undifferentiated
      sarcomatous component with necrosis. Atypical smooth muscle differentiation was
      also detected. Additional tumor sampling revealed the presence of a WDL
      component. Immunohistochemical analysis of the pleomorphic sarcomatous component
      showed positive staining for MDM2 and CDK4, and negative staining for alpha
      smooth muscle actin (alphaSMA) and desmin. The smooth muscle component was
      positive for alphaSMA and desmin, and negative for MDM2 and CDK4. Extension from
      primary retroperitoneal sarcoma was not proved. We diagnosed of DL with
      leiomyosarcomatous differentiation. VIRTUAL SLIDES: The virtual slide(s) for this
      article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1484291498104021.

PMID- 23971888
TI  - Ligand-controlled remarkable regio- and stereodivergence in intermolecular
      hydrosilylation of internal alkynes: experimental and theoretical studies.
AB  - The first highly efficient ligand-controlled regio- and stereodivergent
      intermolecular hydrosilylations of internal alkynes have been disclosed. Cationic
      ruthenium complexes [Cp*Ru(MeCN)3](+) and [CpRu(MeCN)3](+) have been demonstrated
      to catalyze intermolecular hydrosilylations of silyl alkynes to form a range of
      vinyldisilanes with excellent but opposite regio- and stereoselectivity, with the
      former being alpha anti addition and the latter beta syn addition. The use of a
      silyl masking group not only provides sufficient steric bulk for high selectivity
      but also leads to versatile product derivatizations toward a variety of useful
      building blocks. DFT calculations suggest that the reactions proceed by a
      mechanism that involves oxidative hydrometalation, isomerization, and reductive
      silyl migration. The energetics of the transition states and intermediates varies
      dramatically with the catalyst ligand (Cp* and Cp). Theoretical studies combined
      with experimental evidence confirm that steric effect plays a critical role in
      governing the regio- and stereoselectivity, and the interplay between the
      substituent in the alkyne (e.g., silyl group) and the ligand ultimately
      determines the observed remarkable regio- and stereodivergence. 

PMID- 23971889
TI  - Written feedback and continuity of learning in a geographically distributed
      medical education program.
AB  - BACKGROUND: The provision of effective feedback on clinical performance for
      medical students is important for their continued learning. Written feedback is
      an underutilised medium for linking clinical performances over time. AIMS: The
      aim of this study is to investigate how clinical supervisors construct
      performance orientated written feedback and learning goals for medical students
      in a geographically distributed medical education (GDME) programme. METHODS: This
      qualitative study uses textual analysis to examine the structure and content of
      written feedback statements in 1000 mini-CEX records from 33 Australian
      undergraduate medical students during their 36 week GDME programme. The students
      were in their second clinical year. RESULTS: Forty percent of mini-CEX records
      contained written feedback statements. Within these statements, 80% included
      comments relating to student clinical performance. The way in which written
      feedback statements were recorded varied in structure and content. Only 16% of
      the statements contained student learning goals focused on improving a student's
      clinical performance over time. Very few of the written feedback statements
      identified forward-focused learning goals. CONCLUSION: Training clinical
      supervisors in understanding how their feedback contributes to a student's
      continuity of learning across their GDME clinical placements will enable more
      focused learning experiences based on student need. To enhance student learning
      over time and place, effective written feedback should contain focused, coherent
      phrases that help reflection on current and future clinical performance. It also
      needs to provide enough detail for other GDME clinical supervisors to understand
      current student performance and plan future directions for their teaching.

PMID- 23971890
TI  - Cracks in problem-based learning: what is your action plan?
AB  - BACKGROUND: Problem-based learning (PBL) as an educational approach has been
      adopted by medical and health sciences faculties worldwide. Successful
      implementation of these curricula may, however, end a few years later with
      several problems reflecting cracks in curriculum maintenance. AIMS: The aim of
      this article is to discuss these problems, their possible causes and what action
      can be taken to maintain effective curriculum delivery. METHODS: We reviewed the
      current literature, recent Association for Medical Education in Europe
      conferences' sessions on PBL, explored curriculum design approaches and problems
      (cracks) identified in PBL programs that may occur a few years after successful
      implementation. We have also reflected on our collective experience in a number
      of universities to develop these tips. RESULTS: Incorporating the methods
      described, we have developed the following 12 tips: (1) Pay attention to training
      new staff for PBL, (2) Maintain the briefing/debriefing sessions, (3) Review the
      PBL material and program in light of the previous year's feedback, (4) Monitor
      the delivery of the program, (5) Review management of the PBL program, (6)
      Encourage research and publications in PBL, (7) Ensure that assessment reflects
      PBL principles, (8) Refrain from adding new lectures to the timetable, (9) Reward
      contributions to on-going curriculum maintenance, (10) Provide on-going and
      advanced professional development tutor training, (11) Make explicit (and
      develop) students' skills required for PBL and (12) Attend to conflict and group
      dysfunction. CONCLUSIONS: Being vigilant of possible cracks (erosion) in the PBL
      curriculum that may occur a few years after successful implementation is
      mandatory. Erosion of PBL can be minimized or avoided if these tips can be
      applied.

PMID- 23971892
TI  - Theoretical study on the conformation and aromaticity of regular and singly N
      confused [28]hexaphyrins.
AB  - Structures and electronic states of regular and singly N-confused
      [28]hexaphyrins(1.1.1.1.1.1) were thoroughly studied with the aid of DFT
      calculations. To obtain systematic information, all the conceivable structures
      (450 structures in total) were examined. Unlike the [26]hexaphyrins(1.1.1.1.1.1)
      reported previously (J. Org. Chem. 2010, 75, 8213-8223), the electronic states of
      [28]hexaphyrins were highly affected by their conformations. The planar
      conformers (dumbbell, rectangular, triangular) show Huckel antiaromaticity, while
      the singly twisted conformers show Mobius aromaticity. Figure-eight structures
      correspond to the doubly twisted structures and show nonaromaticity. Disruption
      of annulenic circuits in singly N-confused [28]hexaphyrins caused weakening of
      both aromatic and antiaromatic characteristics. Relative stabilities among
      conformers were mainly governed by the intramolecular hydrogen bonds and
      secondarily affected by the steric factors. In addition, interconversion pathways
      among conformers were proposed on the basis of calculations on singly N-confused
      [28]hexaphyrins. 

PMID- 23971891
TI  - Photocatalytic nanolithography of self-assembled monolayers and proteins.
AB  - Self-assembled monolayers of alkylthiolates on gold and alkylsilanes on silicon
      dioxide have been patterned photocatalytically on sub-100 nm length-scales using
      both apertured near-field and apertureless methods. Apertured lithography was
      carried out by means of an argon ion laser (364 nm) coupled to cantilever-type
      near-field probes with a thin film of titania deposited over the aperture.
      Apertureless lithography was carried out with a helium-cadmium laser (325 nm) to
      excite titanium-coated, contact-mode atomic force microscope (AFM) probes. This
      latter approach is readily implementable on any commercial AFM system.
      Photodegradation occurred in both cases through the localized photocatalytic
      degradation of the monolayer. For alkanethiols, degradation of one thiol exposed
      the bare substrate, enabling refunctionalization of the bare gold by a second,
      contrasting thiol. For alkylsilanes, degradation of the adsorbate molecule
      provided a facile means for protein patterning. Lines were written in a protein
      resistant film formed by the adsorption of oligo(ethylene glycol)-functionalized
      trichlorosilanes on glass, leading to the formation of sub-100 nm adhesive,
      aldehyde-functionalized regions. These were derivatized with
      aminobutylnitrilotriacetic acid, and complexed with Ni(2+), enabling the binding
      of histidine-labeled green fluorescent protein, which yielded bright fluorescence
      from 70-nm-wide lines that could be imaged clearly in a confocal microscope. 

PMID- 23971893
TI  - Predictors of readiness to change young adult drug use in community health
      settings.
AB  - This study evaluated readiness to change drug use in young adult patients aged 18
      25 years who were provided screening and brief intervention as part of a
      Substance Abuse and Mental Health Services Administration (SAMHSA) Treatment
      Capacity Expansion Project. Non-treatment-seeking young adults at risk for drug
      problems (n = 1,560) were assessed for readiness to change. Structural equation
      modeling examined latent constructs: emotional distress, age, drug use severity,
      criminal behavior, gender, and race/ethnicity. Drug use severity fully mediated
      the relationship between emotional distress and readiness. In addition, females
      and young adults with more severe drug problems may be more amenable to behavior
      change. 

PMID- 23971895
TI  - Unmet healthcare need among women who use methamphetamine in San Francisco.
AB  - Methamphetamine use has increased substantially in the United States since the
      1990s. Few studies have examined the healthcare service needs of women who use
      methamphetamine. This study describes unmet medical needs in a community-based
      sample of women who use methamphetamine in San Francisco, CA. Women who use
      methamphetamine were recruited in San Francisco and participated in a computer
      assisted survey (N = 298 HIV-negative women). Multivariate analysis was performed
      to explore associations among sociodemographic variables, drug use, use of health
      and social services, and unmet healthcare need across three domains: chronic
      health problems, dermatologic problems, and women's preventive healthcare. Sixty
      nine percent of participants reported a need for care for a chronic health
      condition, and 31% of them had an unmet need for care, in the last six months.
      Thirty-five percent of participants reported a need for dermatologic healthcare,
      and 66% had an unmet need for care in the last 6 months. Ninety-two percent of
      participants reported a need for women's preventive healthcare and 46% had an
      unmet need for care in the last year. Women who reported having a healthcare
      provider had lower odds of reporting an unmet need for a chronic health condition
      or women's preventive healthcare. Women who used a case manager had lower odds of
      having an unmet need for dermatologic care. A significant proportion of women who
      use methamphetamine in this sample had an unmet need for women's preventive
      healthcare, and overall these women had a significant unmet need for healthcare.
      These findings suggest that contact with a healthcare provider or a caseworker
      could help to expand access to healthcare for this vulnerable population. 

PMID- 23971894
TI  - Health and social problems associated with prescription opioid misuse among a
      diverse sample of substance-using MSM.
AB  - This study examines associations between prescription opioid misuse and
      demographics, substance use, sexual behavior, and related health and social
      problems. Baseline data were collected between 2008 and 2010 from 515 high risk
      men who have sex with men, ages 18-55, in the Miami-Ft. Lauderdale metropolitan
      area who reported heavy substance use and HIV risk in the past 90 days.
      Prescription opioid misuse was associated with other substance use, drug
      injection, substance dependence, and history of arrest. Implications,
      limitations, and directions for future study are discussed.

PMID- 23971896
TI  - A new iced tea base herbal beverage with Spergularia rubra extract: metabolic
      profile stability and in vitro enzyme inhibition.
AB  - Beverages are an ideal format to offer nutrients, specific health-promoting
      functionality, and desirable sensory attributes to consumers. Taking into account
      previous research on Spergularia rubra (L.) J. Presl & C. Presl, the aim of this
      work was to describe the chemistry and biochemistry associated with the
      production of a new iced tea base herbal beverage containing a hydroethanolic
      extract of this species, including both naturally occurring and added components.
      Phenolic compounds of S. rubra hydroethanolic extract and of the iced tea base
      herbal beverage were determined by HPLC-DAD. Thirty compounds, comprising
      nonacylated C-glycosyl flavones, C-glycosyl flavones acylated with aromatic
      acids, and C-glycosyl flavones acylated with aliphatic acids, were identified,
      being essentially represented by apigenin derivatives. Organic acids of both
      samples were determined by HPLC-UV, malic acid being the major one. A strong
      inhibition of alpha-glucosidase, acetylcholinesterase, and butyrylcholinesterase
      was observed. Furthermore, the influence of the pH of the digestive tube on the
      chemical composition of both extract and iced tea base herbal beverage and,
      consequently, on their biological activity, was assessed. In a general way, pH
      variation significantly decreased (p < 0.05) the metabolites content and enzymes
      inhibitory capacity. Nevertheless, the beverage enriched with S. rubra extract
      represents a valuable addition to consumer's health and nutrition, once the loss
      of activity is lower than the one verified for the base iced tea. Thus, the
      results suggest that the ingestion of this beverage could be of potential
      interest for several chronic disorders, particularly Alzheimer's disease. 

PMID- 23971897
TI  - Diagnosis of acromegaly: state of the art.
AB  - INTRODUCTION: Biochemical diagnosis of acromegaly relies on measurement of
      insulin-like growth factor-1 (IGF-1) and growth hormone (GH). An elevated IGF-1
      level above the age- and gender-specific normal range and nonsuppression of GH to
      oral glucose load to a nadir < 0.4 ng/ml in sensitive assays are currently
      considered diagnostic of acromegaly. Lack of normative data for both IGF-1 and GH
      across a wide range of populations and ethnicities, interassay and intraassay
      laboratory variability, pulsatility of GH secretion, and effects of medications
      and hormones may confound interpretation of these biochemical tests. AREAS
      COVERED: Clinical situations in which acromegaly should be suspected and/or
      investigated. Strengths and limitations of current IGF-1/GH assays are discussed.
      Clinical scenarios with discordant GH suppression test and IGF-1 levels and,
      briefly, acromegaly in pregnancy, prolactin-cosecreting tumors, familial
      acromegaly, and nonpituitary acromegaly are also discussed. EXPERT OPINION: Serum
      IGF-1 is the cornerstone and in most cases the stand-alone test in the diagnosis
      and follow-up in patients with acromegaly. Diagnosis depends on the accurate and
      reliable measurement of serum IGF-1. GH suppression testing is currently used in
      limited clinical setting. Standardization of IGF-1 assay and development of
      normative data across a wide population base are needed. Newer bioassays for IGF
      1 hold promise for future.

PMID- 23971898
TI  - Novel diagnostic and prognostic biomarkers in biliary tract cancer.
AB  - INTRODUCTION: The worldwide incidence of biliary tract carcinoma (BTC, tumours of
      the bile ducts and gall-bladder) continues to rise, with the only potentially
      curative treatment remaining surgical resection or transplantation, possible in
      only a minority of patients. Late presentation and a paucity of effective
      treatments mandate the development of techniques for early lesion detection.
      AREAS COVERED: This article reviews currently available biomarkers for the
      diagnosis and prognosis of BTC, as well as recently published studies describing
      novel serum, bile and urinary biomarkers. EXPERT OPINION: The incorporation of
      novel analysis techniques, such as digital image analysis and fluorescence in
      situ hybridization, into existing management algorithms enhances the accuracy of
      brush cytology taken at the time of therapeutic endoscopy. However, a key goal is
      the discovery of reliable non-invasive biomarkers with high sensitivity and
      specificity. Recent advances in gene sequencing and expression, clonal evolution
      and tumour heterogeneity in other cancers should advance understanding of BTC
      tumour biology and facilitate biomarker discovery.

PMID- 23971900
TI  - Design criteria for polyazine extractants to separate An(III) from Ln(III.).
AB  - Although polyazine extractants have been extensively studied as agents for
      partitioning trivalent actinides from lanthanides, an explanation for why certain
      azine compositions succeed and others fail is lacking. To address this issue,
      density functional theory calculations were used to evaluate fundamental
      properties (intrinsic binding affinity for a representative trivalent f-block
      metal, basicity, and hardness) for prototype azine donors pyridine, pyridazine,
      pyrimidine, pyrazine, 1,2,3-triazine, 1,2,4-triazine, and 1,3,5-triazine, as well
      as perform conformational analyses of bisazine chelates formed by directly
      connecting two donors together. The results provide criteria that both
      rationalize the behavior of known extractants, TERPY, TPTZ, hemi-BTP, BTP, BTBP,
      and BTPhen, and predict a new class of extractants based on pyridazine donor
      groups. 

PMID- 23971901
TI  - Self-assembly mechanism of folate-templated mesoporous silica.
AB  - A method to form ordered mesoporous silica based on the use of folate
      supramolecular templates has been developed. Evidence based on in situ small
      angle X-ray scattering (SAXS), electron microscopy, infrared spectroscopy, and in
      situ conductivity measurements are used to investigate the organic-inorganic
      interactions and synthesis mechanism. The behavior of folate molecules in
      solution differs distinctively from that of surfactants commonly used for the
      preparation of ordered mesoporous silica phases, notably with the absence of a
      critical micellar concentration. In situ SAXS studies reveal fluctuations in X
      ray scattering intensities consistent with the condensation of the silica
      precursor surrounding the folate template and the growth of the silica
      mesostructure in the initial stages. High-angle X-ray diffraction shows that the
      folate template is well-ordered within the pores even after a few minutes of
      synthesis. Direct structural data for the self-assembly of folates into chiral
      tetramers within the pores of mesoporous silica provide evidence for the in
      register stacking of folate tetramers, resulting in a chiral surface of rotated
      tetramers, with a rotation angle of 30 degrees . Additionally, the self-assembled
      folates within pores were capable of adsorbing a considerable amount of CO2 gas
      through the cavity space of the tetramers. The study demonstrates the validity of
      using a naturally occurring template to produce relevant and functional
      mesoporous materials. 

PMID- 23971902
TI  - Rapid and effective oxidative pretreatment of woody biomass at mild reaction
      conditions and low oxidant loadings.
AB  - BACKGROUND: One route for producing cellulosic biofuels is by the fermentation of
      lignocellulose-derived sugars generated from a pretreatment that can be
      effectively coupled with an enzymatic hydrolysis of the plant cell wall. While
      woody biomass exhibits a number of positive agronomic and logistical attributes,
      these feedstocks are significantly more recalcitrant to chemical pretreatments
      than herbaceous feedstocks, requiring higher chemical and energy inputs to
      achieve high sugar yields from enzymatic hydrolysis. We previously discovered
      that alkaline hydrogen peroxide (AHP) pretreatment catalyzed by copper(II) 2,2?
      bipyridine complexes significantly improves subsequent enzymatic glucose and
      xylose release from hybrid poplar heartwood and sapwood relative to uncatalyzed
      AHP pretreatment at modest reaction conditions (room temperature and atmospheric
      pressure). In the present work, the reaction conditions for this catalyzed AHP
      pretreatment were investigated in more detail with the aim of better
      characterizing the relationship between pretreatment conditions and subsequent
      enzymatic sugar release. RESULTS: We found that for a wide range of pretreatment
      conditions, the catalyzed pretreatment resulted in significantly higher glucose
      and xylose enzymatic hydrolysis yields (as high as 80% for both glucose and
      xylose) relative to uncatalyzed pretreatment (up to 40% for glucose and 50% for
      xylose). We identified that the extent of improvement in glucan and xylan yield
      using this catalyzed pretreatment approach was a function of pretreatment
      conditions that included H2O2 loading on biomass, catalyst concentration, solids
      concentration, and pretreatment duration. Based on these results, several
      important improvements in pretreatment and hydrolysis conditions were identified
      that may have a positive economic impact for a process employing a catalyzed
      oxidative pretreatment. These improvements include identifying that: (1)
      substantially lower H2O2 loadings can be used that may result in up to a 50-65%
      decrease in H2O2 application (from 100 mg H2O2/g biomass to 35-50 mg/g) with only
      minor losses in glucose and xylose yield, (2) a 60% decrease in the catalyst
      concentration from 5.0 mM to 2.0 mM (corresponding to a catalyst loading of 25
      MUmol/g biomass to 10 MUmol/g biomass) can be achieved without a subsequent loss
      in glucose yield, (3) an order of magnitude improvement in the time required for
      pretreatment (minutes versus hours or days) can be realized using the catalyzed
      pretreatment approach, and (4) enzyme dosage can be reduced to less than 30 mg
      protein/g glucan and potentially further with only minor losses in glucose and
      xylose yields. In addition, we established that the reaction rate is improved in
      both catalyzed and uncatalyzed AHP pretreatment by increased solids
      concentrations. CONCLUSIONS: This work explored the relationship between reaction
      conditions impacting a catalyzed oxidative pretreatment of woody biomass and
      identified that significant decreases in the H2O2, catalyst, and enzyme loading
      on the biomass as well as decreases in the pretreatment time could be realized
      with only minor losses in the subsequent sugar released enzymatically. Together
      these changes would have positive implications for the economics of a process
      based on this pretreatment approach.

PMID- 23971903
TI  - Anticoagulant failure in coagulopathic patients: PTT confounding and other
      pitfalls.
AB  - INTRODUCTION: Devastating thromboses can complicate heparin-induced
      thrombocytopenia (HIT) and disseminated intravascular coagulation (DIC). In these
      disorders, acquired abnormalities of the partial thromboplastin time (PTT) and
      international normalized ratio (INR) can confound monitoring of PTT- and INR
      adjusted anticoagulant therapies, contributing to treatment failure. AREAS
      COVERED: Illustrative patient cases of anticoagulant failure due to PTT and INR
      confounding are discussed. Four different scenarios of thrombosis progression
      associated with inappropriate anticoagulant interruption/underdosing,
      contributing to ischemic limb necrosis, are presented: i) PTT confounding of
      heparin therapy of warfarin-associated microthrombosis complicating cancer
      hypercoagulability; ii) PTT confounding of direct thrombin inhibitor (DTI)
      therapy complicating HIT-associated DIC; iii) INR confounding during argatroban
      warfarin overlap of HIT-associated deep-vein thrombosis; and iv) PTT confounding
      of anticoagulant therapy during acute DIC/hepatic necrosis-ischemic limb necrosis
      syndrome. EXPERT OPINION: Abnormal coagulation test results at pre-treatment
      baseline can provide an important clue regarding the risk of subsequent
      anticoagulant failure due to PTT or INR confounding. Greater awareness of the
      potential for anticoagulant failure due to PTT and INR confounding could assist
      clinicians in management of prothrombotic coagulopathies, for example, by
      choosing alternative anticoagulants (e.g., fondaparinux, danaparoid) that are not
      monitored by global coagulation assays, or by obtaining specific drug levels
      (anti-factor Xa levels, DTI levels).

PMID- 23971904
TI  - The SAKK cancer-specific geriatric assessment (C-SGA): a pilot study of a brief
      tool for clinical decision-making in older cancer patients.
AB  - BACKGROUND: Recommendations from international task forces on geriatric
      assessment emphasize the need for research including validation of cancer
      specific geriatric assessment (C-SGA) tools in oncological settings. This study
      was to evaluate the feasibility of the SAKK Cancer-Specific Geriatric Assessment
      (C-SGA) in clinical practice. METHODS: A cross sectional study of cancer patients
      >=65 years old (N = 51) with pathologically confirmed cancer presenting for
      initiation of chemotherapy treatment (07/01/2009-03/31/2011) at two oncology
      departments in Swiss canton hospitals: Kantonsspital Graubunden (KSGR N = 25),
      Kantonsspital St. Gallen (KSSG N = 26). Data was collected using three
      instruments, the SAKK C-SGA plus physician and patient evaluation forms. The SAKK
      C-SGA includes six measures covering five geriatric assessment domains
      (comorbidity, function, psychosocial, nutrition, cognition) using a mix of
      medical record abstraction (MRA) and patient interview. Five individual domains
      and one overall SAKK C-SGA score were calculated and dichotomized as below/above
      literature-based cut-offs. The SAKK C-SGA was evaluated by: patient and physician
      estimated time to complete, ease of completing, and difficult or unanswered
      questions. RESULTS: Time to complete the patient questionnaire was considered
      acceptable by almost all (>=96%) patients and physicians. Patients reported
      slightly shorter times to complete the questionnaire than physicians (17.33 +/-
      7.34 vs. 20.59 +/- 6.53 minutes, p = 0.02). Both groups rated the patient
      questionnaire as easy/fairly easy to complete (91% vs. 84% respectively, p =
      0.14) with few difficult or unanswered questions. The MRA took on average 8.32 +/
      4.72 minutes to complete. Physicians (100%) considered time to complete MRA
      acceptable, 96% rated it as easy/fairly easy to complete. Individual study site
      populations differed on health-related characteristics (excellent/good physician
      rated general health KSGR 71% vs. KSSG 32%, p = 0.007). The overall mean C-SGA
      score was 2.4 +/- 1.12. Patients at KSGR had lower C-SGA scores (2.00 +/- 1.19
      vs. 2.81 +/- 0.90, p = 0.009) and a smaller proportion (28% vs.65%, p = 0.008)
      was above the C-SGA cut-off score compared to KSSG. CONCLUSIONS: These results
      suggest the SAKK C-SGA is a feasible practical tool for use in clinical practice.
      It demonstrated discriminative ability based on objective geriatric assessment
      measures, but additional investigations on use for clinical decision-making are
      warranted. The SAKK C-SGA also provides important usable domain information for
      intervention to optimize outcomes in older cancer patients.

PMID- 23971907
TI  - Neapolitan societies.

PMID- 23971906
TI  - Enhanced cytotoxicity from deoxyguanosine-enriched T-oligo in prostate cancer
      cells.
AB  - Prostate cancer represents approximately 10 percent of all cancer cases in men
      and accounts for more than a quarter of all cancer types. Advances in
      understanding the molecular mechanisms of prostate cancer progression, however,
      have not translated well to the clinic. Patients with metastatic and hormone
      refractory disease have only palliative options for treatment, as chemotherapy
      seldom produces durable or complete responses, highlighting the need for novel
      therapeutic approaches. T-oligo, a single-stranded deoxyribonucleic acid with
      partial sequence homology to human telomeric DNA, has elicited cytostatic and/or
      cytotoxic effects in multiple cancer cell types. In contrast, normal primary
      cells of varying tissue types are resistant to cytotoxic actions of T-oligo,
      underscoring its potential utility as a novel targeted cancer therapeutic.
      Mechanistically, T-oligo is hypothesized to interfere with normal telomeric
      structure and form G-quadruplex structures, thereby inducing genomic stress in
      addition to aberrant upregulation of DNA damageresponse pathways. Here, we
      present data demonstrating the enhanced effectiveness of a deoxyguanosine
      enriched sequence of T-oligo, termed (GGTT)4, which elicits robust cytotoxic
      effects in prostate cancer cells at lower concentrations than the most recent T
      oligo sequence (5'-pGGT TAG GTG TAG GTT T 3') described to date and used for
      comparison in this study, while exerting no cytotoxic actions on nontransformed
      human prostate epithelial cells. Additionally, we provide evidence supporting the
      T-oligo induced activation of cJun N-terminal kinase (JNK) signaling in prostate
      cancer cells consistent with G-quadruplex formation, thereby significantly
      advancing the understanding of the T-oligo mechanism of action. 

PMID- 23971908
TI  - Sequence-specific cleavage of BM2 gene transcript of influenza B virus by 10-23
      catalytic motif containing DNA enzymes significantly inhibits viral RNA
      translation and replication.
AB  - One of the hallmarks of progression of influenza virus replication is the step
      involving the virus uncoating that occurs in the host cytoplasm. The BM2 ion
      channel protein of influenza B virus is highly conserved and is essentially
      required during the uncoating processes of virus, thus an attractive target for
      designing antiviral drugs. We screened several DNA enzymes (Dzs) containing the
      10-23 catalytic motif against the influenza B virus BM2 RNA. Dzs directed against
      the predicted single-stranded bulge regions showed sequence-specific cleavage
      activities. The Dz209 not only showed significant intracellular reduction of BM2
      gene expression in transient-expression system but also provided considerable
      protection against influenza B virus challenge in MDCK cells. Our findings
      suggest that the Dz molecule can be used as selective and effective inhibitor of
      viral RNA replication, and can be explored further for development of a potent
      therapeutic agent against influenza B virus infection. 

PMID- 23971905
TI  - Selection and characterization of single stranded DNA aptamers for the hormone
      abscisic Acid.
AB  - The hormone abscisic acid (ABA) is a small molecule involved in pivotal
      physiological functions in higher plants. Recently, ABA has been also identified
      as an endogenous hormone in mammals, regulating different cell functions
      including inflammatory processes, stem cell expansion, insulin release, and
      glucose uptake. Aptamers are short, single-stranded (ss) oligonucleotidesable to
      recognize target molecules with high affinity. The small size of the ABA molecule
      represented a challenge for aptamer development and the aim of this study was to
      develop specific anti-ABA DNA aptamers. Biotinylated abscisic acid (bio-ABA) was
      immobilized on streptavidin-coated magnetic beads. DNA aptamers against bio-ABA
      were selected with 7 iterative rounds of the systematic evolution of ligands by
      exponential enrichment method (SELEX), each round comprising incubation of the
      ABA-binding beads with the ssDNA sequences, DNA elution, electrophoresis, and
      polymerase chain reaction (PCR) amplification. The PCR product was cloned and
      sequenced. The binding affinity of several clones was determined using bio-ABA
      immobilized on streptavidin-coated plates. Aptamer 2 and aptamer 9 showed the
      highest binding affinity, with dissociation constants values of 0.98 +/- 0.14 MUM
      and 0.80 +/- 0.07 MUM, respectively. Aptamers 2 and 9 were also able to bind
      free, unmodified ABA and to discriminate between different ABA enantiomers and
      isomers. Our findings indicate that ssDNA aptamers can selectively bind ABA and
      could be used for the development of ABA quantitation assays.

PMID- 23971909
TI  - Stability and fragmentation of the activity rhythm across the sleep-wake cycle:
      the importance of age, lifestyle, and mental health.
AB  - The rhythms of activity across the 24-h sleep-wake cycle, determined in part by
      the circadian clock, change with aging. Few large-scale studies measured the
      activity rhythm objectively in the general population. The present population
      based study in middle-aged and elderly persons evaluated how activity rhythms
      change with age, and additionally investigated sociodemographics, mental health,
      lifestyle, and sleep characteristics as determinants of rhythms of activity.
      Activity rhythms were measured objectively with actigraphy. Recordings of at
      least 96 h (138 +/- 14 h, mean +/- SD) were collected from 1734 people (age: 62
      +/- 9.4 yrs) participating in the Rotterdam Study. Activity rhythms were
      quantified by calculating interdaily stability, i.e., the stability of the rhythm
      over days, and intradaily variability, i.e., the fragmentation of the rhythm
      relative to its 24-h amplitude. We assessed age, gender, presence of a partner,
      employment, cognitive functioning, depressive symptoms, body mass index (BMI),
      coffee use, alcohol use, and smoking as determinants. The results indicate that
      older age is associated with a more stable 24-h activity profile (beta = 0.07, p
      = 0.02), but also with a more fragmented distribution of periods of activity and
      inactivity (beta = 0.20, p < 0.001). Having more depressive symptoms was related
      to less stable (beta = -0.07, p = 0.005) and more fragmented (beta = 0.10, p <
      0.001) rhythms. A high BMI and smoking were also associated with less stable
      rhythms (BMI: beta = -0.11, p < 0.001; smoking: beta = -0.11, p < 0.001) and more
      fragmented rhythms (BMI: beta = 0.09, p < 0.001; smoking: beta = 0.11, p <
      0.001). We conclude that with older age the 24-h activity rhythm becomes more
      rigid, whereas the ability to maintain either an active or inactive state for a
      longer period of time is compromised. Both characteristics appear to be important
      for major health issues in old age.

PMID- 23971910
TI  - Criterion for evaluating the predictive ability of nonlinear regression models
      without cross-validation.
AB  - We propose predictive performance criteria for nonlinear regression models
      without cross-validation. The proposed criteria are the determination coefficient
      and the root-mean-square error for the midpoints between k-nearest-neighbor data
      points. These criteria can be used to evaluate predictive ability after the
      regression models are updated, whereas cross-validation cannot be performed in
      such a situation. The proposed method is effective and helpful in handling big
      data when cross-validation cannot be applied. By analyzing data from numerical
      simulations and quantitative structural relationships, we confirm that the
      proposed criteria enable the predictive ability of the nonlinear regression
      models to be appropriately quantified. 

PMID- 23971911
TI  - Putting sex on the table: sex, sexuality and masculinity among HIV-positive men
      in Nairobi, Kenya.
AB  - Psychosocial support groups offer an important space for people living with HIV
      to pursue greater wellbeing as they learn how to accept and live with their HIV
      status. They are critical for the cultivation of responsible and adherent
      patients. Occasionally, support groups provide spaces where members are
      encouraged to discuss sexual struggles related to being HIV-positive, including
      sexual performance issues, sexual relationships, fertility desires and
      communicating with sexual partners. This paper examines an HIV-positive men's sex
      therapy support group at Kenyatta National Hospital in Nairobi, Kenya, where HIV
      positive men access information about HIV and treatment, while getting tips on
      restoring sexual functioning and improving sexual gratification from medical
      experts, peer counsellors and fellow group members. In the group setting, members
      worked to rediscover and reconstruct masculinity under the guidance of a range of
      experts, while focusing on regaining or improving sexual prowess. 

PMID- 23971912
TI  - Mn8 cluster with ferrocene-1,1'-dicarboxylate ligation: single-molecule magnetism
      with multiple external redox centers.
AB  - The syntheses, structures, and magnetic properties are reported of a new Mn8
      cluster obtained from the reaction of ferrocene-1,1'-dicarboxylic acid (fdcH2)
      with [Mn12O12(O2CMe)16(H2O)4] and mononuclear Mn salts under different conditions
      and limited light exposure. The product was obtained in two forms:
      [Mn8O4(fdc)6(DMF)2(H2O)2] (1) and [Mn8O4(fdc)6(DMF)4] (2), differing in the bound
      solvent ligands. The structures are otherwise almost identical, comprising very
      similar cores that both contain 4Mn(III) and 4Mn(II) atoms bridged by four O(2-)
      ions and six fdc(2-) groups. The [Mn(III)4Mn(II)4(MU4-O)4] cores have virtual Td
      symmetry and can be described as a central [Mn(III)4(MU4-O)4](4+) cubane unit
      whose four O(2-) ions are MU4, because they each attach to an external Mn(II)
      atom. Peripheral ligation about the core is provided by six bridging fdc(2-)
      groups and the terminal solvent ligands, one each on the Mn(II) atoms. The
      differences in solvent ligands between 1 and 2, and different packing from the
      different crystal space groups, lead to significant differences in metric
      parameters within the core, which are reflected in significantly different
      magnetic properties. Variable-temperature, solid-state dc and ac susceptibility
      measurements reveal the clusters to be predominantly antiferromagnetically
      coupled, and to possess ground state spin values of S = 5 and S = 2 for 1 and 2,
      respectively. The difference in ground states is assigned to the small but
      distinct structural differences seen in the central cubane. Alternating current
      (AC) susceptibility data indicate 1 and 2 to be new single-molecule magnet, and
      this was confirmed by magnetization versus direct current (DC) field scans on a
      single crystal of 1.4DMF.4H2O, which exhibited hysteresis. 

PMID- 23971913
TI  - Thresholds for platelet reactivity to predict clinical events after coronary
      intervention are different in patients with and without diabetes mellitus.
AB  - Patients with diabetes mellitus (DM) have increased baseline platelet reactivity
      and impaired response to antiplatelet drugs, compared to non-diabetics. Aim of
      the present study was to investigate whether thresholds for high platelet
      reactivity (HPR) that predict clinical outcomes after percutaneous coronary
      intervention (PCI) are similar in diabetic compared to non-diabetic patients. A
      total of 640 (32.6% with DM) consecutive patients taking aspirin and clopidogrel
      undergoing elective PCI were recruited. Platelet reactivity was measured
      immediately before the procedure with the VerifyNow P2Y12 assay. Primary end
      point was the 30-day incidence of major adverse cardiac events (MACE) in relation
      to the presence of DM and to P2Y12 reaction units (PRU) distribution. The optimal
      cut-off to predict 30-day MACE was a PRU value of >256 in diabetics, and a PRU
      value of >229 in non-diabetics. Accordingly, we redefined HPR on the basis of
      these two specific thresholds (HPR-ST), now including 60/209 (29%) diabetic
      patients with PRU >256, and 130/431 (30%) non-diabetic patients with PRU >229.
      HPR-ST discriminates significantly (p < 0.001) patients with and without MACE,
      with a diagnostic accuracy of 73%. The combination of DM and HPR-ST resulted in
      the highest incidence of MACE (23.3%; p for trend <0.001). At multivariate
      analysis, HPR-ST was the strongest independent predictor of 30-day MACE (odds
      ratio 4.80, 95% confidence interval 2.58-8.93; p < 0.001). Redefining HPR based
      on specific thresholds for patients with and without DM significantly improves
      prediction of MACE post-PCI. Patients with HPR-ST, especially in the presence of
      DM, are at increased risk for ischemic events and may benefit from more
      aggressive antiplatelet strategies.

PMID- 23971914
TI  - In vivo modulation of avidity in highly sensitive CD8(+) effector T cells
      following viral infection.
AB  - Numerous studies have demonstrated a critical role for T cell avidity in
      predicting in vivo efficacy. Even though the measurement of avidity is now a
      routine assessment for the analysis of effector and memory T cell populations,
      our understanding of how this property is controlled in vivo at both the
      population and individual cell levels is limited. Our previous studies have
      identified high avidity as a property of the initial effector population
      generated in mice following respiratory virus infection. As the response
      progresses, lower avidity cells appear in the effector pool. The studies
      described here investigate the mechanistic basis of this in vivo regulation of
      avidity. We present data supporting in vivo avidity modulation within the early
      high avidity responders that results in a population of lower avidity effector
      cells. Changes in avidity were correlated with decreased lck expression and
      increased sensitivity to lck inhibitors in effector cells present at late versus
      early times postinfection. The possibility of tuning within select individual
      effectors is a previously unappreciated mechanism for the control of avidity in
      vivo.

PMID- 23971915
TI  - Activation of a sigma-SnSn bond at copper, followed by double addition to an
      alkyne.
AB  - Many synthetically useful copper-catalyzed transformations involve the activation
      of apolar or weakly polar sigma-bonds (E-H and E-E' bonds, with E = C, B, Si, Sn,
      etc.). Yet, little is known so far about the associated elementary steps, and it
      is highly desirable to gain better knowledge regarding the way sigma-bonds can be
      activated by copper to help further development in this area. To this end, we
      became interested in investigating the coordination and activation of apolar or
      weakly polar sigma-bonds at copper using chelating assistance. Here we report
      investigations of gold and copper complexes deriving from the diphosphine
      stannane [Ph2P(o-C6H4)Me2Sn-SnMe2(o-C6H4)PPh2] 1. The sigma-SnSn bond of 1
      readily undergoes oxidative addition at both gold and copper, giving bis(stannyl)
      Au(+) and Cu(+) complexes 2 and 3. Coordination of 1 to CuBr leads to the neutral
      complex 4 which features more sigma-SnSn complex character. The ability of
      complex 3 to undergo insertion reactions with alkynes was then examined. With
      methyl propiolate, a clean reaction occurred, and the bis-stannylated alkene
      copper complex 5 was isolated. The structures of ligand 1 and complexes 2-5 have
      been unambiguously determined by multinuclear NMR spectroscopy and
      crystallography. These results substantiate the ability of copper to promote the
      addition of apolar sigma-bonds to CC multiple bonds via a 2e redox sequence and
      draw thereby an unprecedented parallel with the group 10 metals. 

PMID- 23971916
TI  - Using shape anisotropy to toughen disordered nanoparticle assemblies.
AB  - Assemblies of disordered nanoparticles constitute an important class of materials
      that have numerous applications in energy conversion and storage, electronics,
      photonics, and sensing. One major roadblock that limits the widespread
      utilization of disordered nanoparticle assemblies (DNAs) is their poor damage
      tolerance; they fracture under small loads and, thus, have low toughness. The
      absence of fundamental understanding on the mechanical behavior and failure
      mechanism of disordered nanoparticle assemblies makes it even more challenging to
      develop new strategies to toughen these structures without compromising their
      mechanical strength. Here we show the formation of shear bands, highly localized
      regions of mechanical strain that prelude fracture, in disordered assemblies of
      spherical nanoparticles, which bear striking resemblance to the deformation
      mechanism of a different class of disordered materials, metallic glasses. We
      demonstrate that anisotropic nanoparticles greatly suppress shear band formation
      and toughen nanoparticle packings without sacrificing their strength, implying
      that tuning constituent anisotropy can be used to enhance toughness in disordered
      packings of nanoparticles. 

PMID- 23971917
TI  - Mutual interference between intramolecular proton transfer sites through the
      adjoining pi-conjugated system in Schiff bases of double-headed, fused
      salicylaldehydes.
AB  - We synthesized two constitutionally isomeric bis(iminomethyl)-2,6
      dihydroxynaphthalenes, namely, alpha,alpha-diimines 1 and beta,beta-diimines 2,
      which can be formally represented as fused salicylaldimines with resonance
      assisted hydrogen-bonding sites. Spectroscopic data show that the OH/OH, NH/OH,
      and NH/NH forms of 1 were in equilibrium in solution and that the proportion of
      the NH-bearing tautomers increased as the solvent polarity increased. The UV
      spectra of thin solid films of 1 with various types of hydrogen-bonding networks
      differed from one another, and the spectral profiles were markedly temperature
      dependent, whereas the spectra of 1 in the molten state showed quite similar
      profiles. In contrast, 2 existed predominantly as the OH/OH form irrespective of
      the solvent polarity or crystal packing. Quantum chemical calculations suggest
      that the difference between the probabilities of intramolecular proton transfer
      in 1 and 2 can be explained in terms of the interplay between the resonance
      assisted hydrogen-bonding sites and the adjoining pi-conjugated system. 

PMID- 23971918
TI  - [Investigation of the presence of Panton-Valentine leukocidin and clonal
      relationship of community- and hospital-acquired clinical isolates of
      Staphylococcus aureus].
AB  - Staphylococcus aureus is one of the most important pathogens that cause community
      and hospital-acquired infections by its toxins and enzymes. Panton-Valentine
      leukocidin (PVL), a cytotoxin which is especially produced by community-acquired
      S.aureus strains that cause soft tissue and skin infections and pneumonia. PVL
      leads to the destruction on polymorphonuclear cells by necrosis or induce
      apoptosis, so that it has great importance in the virulence of the organism. PVL
      can also exacerbate the clinical course of S.aureus infections and may lead to
      severe complications. Studies show that community-acquired PVL-positive S.aureus
      strains have become prevalent in hospital environments. In this study, we aimed
      to investigate the presence of PVL from hospital- and community-acquired S.aureus
      strains and to determine the clonal relationship between the PVL-positive
      strains. A total of 265 S.aureus strains isolated from different clinical samples
      (wound, blood, tracheal aspirate, urine, drainage, catheter, parasynthesis fluid)
      of which 88 were community-acquired and 177 were hospital-acquired according to
      the CDC criteria were included in the study. Methicillin resistance of the
      strains were investigated by conventional methods, the presence of PVL and mecA
      gene regions by polymerase chain reaction, and clonal relationship among the PVL
      positive S.aureus strains by pulsed-field gel electrophoresis (PFGE). Community
      acquired 12.5% (11/88) and hospital-acquired 43% (76/177) of the strains were
      found resistant to methicillin. Community-acquired (CA) strains were most
      commonly isolated from wound samples (86%), while 34% of hospital-acquired (HA)
      strains were isolated from wound, and 33% were from blood samples. The rate of
      PVL positivity among CA- and HA-strains were found as 15% and 3%, respectively.
      Hospital-acquired PVL-positive strains were isolated from the samples originating
      from pediatric (n= 1) and neurology inpatient clinics and intensive care unit (n=
      3). Thirty nine percent of PVL-positive CA-S.aureus strains were isolated from
      samples originated from internal medicine, 23% from general surgery, 15% from
      dermatology, 15% from orthopedic surgery and 8% from pediatrics outpatient
      clinics. Ninety two percent of PVL-positive CA-S.aureus strains have been
      isolated from wound samples, while 67% of HA-S.aureus strains from wound and 33%
      from blood samples. Five PVL-positive HA- methicillin-sensitive S.aureus strains
      were found clonally-related with each other by PFGE. When the macrorestriction
      patterns were evaluated according to Tenover criteria; three of those isolates
      were indistinguishable, and two were clonally unrelated. There was no clonal
      relationship between community-acquired strains. In conclusion we observed that
      PVL could be detected not only in community-acquired strains but also in hospital
      acquired strains. The spread of PVL-positive strains in the hospital environment
      and even create epidemics, increases the risk of mortality and morbidity.
      Epidemiological studies will help us to understand the clonal spread of CA and HA
      S.aureus strains.

PMID- 23971919
TI  - [Investigation of biofilm-associated antibiotic susceptibilities of methicillin
      resistant staphylococci isolated from catheter-related nosocomial infections].
AB  - Risks for development of local and/or systemic infections are the most important
      complications of catheters that are widely used during hospitalization process.
      The aims of this study were to investigate and compare the antibiotic
      susceptibilities of methicillin-resistant staphylococci isolated from catheters,
      in planktonic and biofilm forms, and to evaluate the antimicrobial effects of
      antibiotics on those forms alone and in combinations. A total of 30 strains [15
      methicillin-resistant Staphylococcus aureus (MRSA) and 15 methicillin-resistant
      coagulase-negative staphylococci (MR-CNS)] isolated from catheter cultures of
      patients hospitalized in different clinics and intensive care units in Baskent
      University Medical School Hospital between 2006-2009, were included in the study.
      The antibiotic sensitivities of MRSA and MR-CNS isolates were investigated in
      vitro in planktonic phase and on sessile cells after biofilm was formed.
      Vancomycin, ciprofloxacin, rifampicin, gentamicin, meropenem, tigecycline,
      linezolid, ceftazidime and cephazolin were used for antibiotic susceptibility
      testing. The sensitivity of planktonic cells to antibiotics was primarily
      investigated, so that minimal inhibitor concentration (MIC) and minimal
      bactericidal concentration (MBC) values were determined by broth microdilution
      method. Afterwards, each strain was transformed to sessile cell in a biofilm
      environment, and MIC and MBC values were also determined for sessile cells.
      Double and triple antibiotic combinations were prepared, the effectiveness of
      combinations were studied on both planktonic and biofilm cells with multiple
      combination bactericidal testing (MCBT) method. The data set obtained from
      planktonic and biofilm cells for each antibiotic analyzed via two proportion z
      test. Statistically significant decreases were found in the sensitivities of
      sessile cells when compared to planktonic cells (p< 0.01). The tests performed
      with the use of double and triple antibiotic combinations also showed the
      susceptibility decrease between planktonic and biofilm forms to be significant in
      most of the combinations (p< 0.01). The comparison of double and triple
      antibiotic combinations against planktonic and sessile cells as determined by the
      inhibition of more than 90% of the strains, revealed no significant difference .
      Vancomycin and tigecycline were the most effective antibiotics for all isolates
      in planktonic and sessile cells. Combinations containing vancomycin and
      rifampicin showed the best activity both double and triple antibiotic
      combinations against biofilm. In conclusion, our data indicated that combination
      therapy, especially double combinations of antibiotics seem to be a rational
      approach for biofilm-related infections. 

PMID- 23971920
TI  - [Comparison of the performances of MTD Gene-Probe(r) test, BACTEC 960TM system
      and Lowenstein-Jensen culture methods in the diagnosis of smear-negative
      tuberculosis cases].
AB  - The aim of this study was to compare the results of nucleic acid amplification
      based MTD (Mycobacterium tuberculosis direct test) Gene-Probe(r) method in
      samples obtained from acid-fast bacilli (ARB) smear-negative patients with
      suspected tuberculosis (TB), with the culture results obtained from automated
      BACTEC 960TM (MGIT) system and Lowenstein-Jensen (LJ) medium. In addition, the
      contribution of molecular methods in early diagnosis of pulmonary TB and the
      effect of radiological prevalence of the disease associated with or without
      cavity to the molecular diagnosis and/or growth time in culture media have been
      evaluated. A total of 107 patients (86 male, 21 female; mean age: 49.89 +/- 17.1
      years, age range: 18-81 years) who were clinically and radiologically suspected
      of having pulmonary TB and/or TB pleurisy, were included in the study. Of the
      samples 65 (60.7%) were sputum, 32 (29.9%) were bronchial aspiration, 5 (4.7%)
      were pleural fluid, and 5 (4.7%) were transthoracic fine needle aspiration biopsy
      materials. Patient samples were cultured in solid LJ media and liquid-based
      BACTEC 960 system (Becton Dickinson Co., USA) in the same working day. Meanwhile,
      MTD Gen-Probe test (Gen-Probe Inc., USA) was studied in two separate working days
      of the week as specified by the laboratory. The samples were incubated until
      positivity was determined in BACTEC 960 system and/or growth was detected in LJ
      medium. Negative cultures were incubated for 42 days and were finalized. When
      mycobacterial growth was determined in the culture, identification of
      M.tuberculosis complex (MTBC) and differentiation from nontuberculous
      mycobacteria were performed by conventional methods and BACTEC 460 NAP test.
      Forty five (42%) patients were diagnosed as pulmonary paranchimal TB (40 were
      active pulmonary TB, 1 was miliary TB and 4 were culture-negative pulmonary TB),
      while 4 (3.7%) patients diagnosed as extrapulmonary TB and 58 (57.9%) patients
      were diagnosed as other pulmonary diseases unrelated with TB. LJ cultures yielded
      positive results in 32 of 45 (71%) pulmonary TB patients, and BACTEC 960 were
      found positive in 84.4% (38/45) of those patients. On the other hand the
      positivity rate of MTD Gen-Probe test was detected as 37.4% (40/107). The
      sensitivity, specificity, positive and negative predictive values for MTD Gen
      Probe test were estimated as 89%, 100%, 100% and 93%, respectively. Those values
      for BACTEC 960 system were found as 82%, 98%, 97% and 88%, and for LJ culture
      method as 71%, 100%, 100% and 83%, respectively. Average periods to make a
      decision for diagnosis of TB by MTD Gen-Probe, BACTEC 960 (MGIT) and LJ culture
      methods were calculated as 2.36 days, 20.11 days and 32.49 days, respectively. In
      comparison of the methods in terms of turnaround times, MTD Gen-Probe test was
      found superior to LJ culture method, however the turnaround times for BACTEC 960
      and LJ culture methods were similar. When the clinical data were evaluated, no
      effect of radiological density of lesion was identified on the diagnosis time of
      molecular test and time of growth in liquid based automated BACTEC system and/or
      LJ culture method. However, LJ culture demonstrated earlier reactivity in
      patients with cavitary lesions. As a result, MTD Gene-Probe test was observed as
      a reliable and rapid method for the early diagnosis of pulmonary TB patients,
      early initiation of therapy, prevention of disease progression and transmission. 

PMID- 23971921
TI  - [MLST types of vancomycin-resistant Enterococcus faecium strains isolated from
      blood cultures].
AB  - Enterococci, particularly vancomycin-resistant enterococci (VRE), are important
      nosocomial pathogens with limited treatment options. Enterococci have low-level
      resistance to penicillins and aminoglycosides and are intrinsically resistant to
      cephalosporins. In addition, they can acquire high-level resistance to beta
      lactam antibiotics, aminoglycosides and glycopeptides. The aim of this study was
      to determine glycopeptide resistance mechanisms and genetic relationships of
      vancomycin-resistant E.faecium strains isolated from blood cultures between 2003
      2009 years by molecular epidemiologic methods. A total of 38 VRE strains isolated
      from blood cultures were included in this study. The isolates were identified by
      conventional methods and Phoenix 100 BD automated system (Becton Dickinson
      Diagnostic Systems, USA) and confirmed by sequence analysis of 16S rRNA
      amplicons. Antibiotic susceptibility tests were performed by the Kirby-Bauer disk
      diffusion method accor-ding to the CLSI standards. MIC values of vancomycin were
      determined in vancomycin resistant strains by E-test (AB Biodisk, Sweden) method.
      Vancomycin resistance genes included vanA, vanB, vanC, and vanD were investigated
      by polymerase chain reaction (PCR) method. Clonal relationship between strains
      was determined by pulsed-field gel electrophoresis (PFGE). Sequence analysis was
      performed for examples selected for multilocus sequence typing (MLST) of each
      pulsotype and subtype. Thirty eight strains of enterococci isolated from blood
      cultures were defined as E.faecium by phenotypic methods and confirmed by 16S
      rRNA sequence analysis. Vancomycin MIC values of strains were determined as > 256
      ug/ml by E test. The vanA gene was detected in all isolates. Clonal relationship
      of 38 isolates E.faecium carrying the vanA gene was determined by PFGE and MLST
      methods. PFGE detected four pulsotypes (A-D) and one sporadic isolate. Twenty
      nine strains belonged to A pulsotype, three strains belonged to B pulsotype, two
      strains belonged to C pulsotype and three strains belonged to D pulsotype. Out of
      29 isolates, eight strains were type A1, nine strains were type A2, six strains
      were type A3, two strains were type A4 and four strains were type A5. MLST
      identified four different sequence types (STs). Twenty nine A pulsotype and its
      subtypes belonged to ST117 (76.3%), three B pulsotype belonged to ST280 (7.9%),
      two C pulsotype belonged to ST18 (5.2%) and three D pulsotype belonged to ST17
      (7.9%). In conclusion, bloodstream infections caused by VRE in our hospital arose
      from a dominant strain belonged to ST117. However, presence of different
      pulsotypes of this strain indicated that the strain had been present in the
      hospital for a long time and had accumulated genetic variations. In addition,
      infections caused by minor pulsotypes were also detected. Therefore for
      prevention and control of the spread of nosocomial infections caused by VRE, it
      is crucial to identify resistance patterns and clonal relationship of these
      organisms. 

PMID- 23971922
TI  - [Salmonella serovars isolated in Turkey up to the end of year 2011].
AB  - Bacteria in Salmonella genus are separated into more than 2600 serovars. It is
      important that the isolated serovars and their sources are known in a certain
      country. This will help the identification of new Salmonella serovars that will
      be isolated later on. Since there is no Salmonella reference center in Turkey,
      Salmonella serovars isolated in Turkey were mainly reported by the articles of
      Aksoycan's manuscripts in various years, and in the list of Toreci and Ang in
      1991. The aim of this meta-analysis was to detect and prepare a list for all the
      Salmonella serovars isolated from human and non-human samples in Turkey up to the
      end of 2011. In creating this serovar list, libraries, personal and institutional
      archives, theses, publication lists, books published after scientific meetings
      and congresses, and international and local periodicals have been explored, and
      members of Turkish Microbiology Society are communicated via the web site of the
      society and personal e-mail addresses, and their publications regarding
      Salmonella serovars were requested. The list also includes the modifications on
      the names and antigenic formulae of the serovars that were carried out in recent
      years. The number of serovars isolated in Turkey up to the end of 2011 is 129.
      Fifty three of them were isolated from humans, 38 from humans and non-human
      samples, and 38 from non-human samples. The total number of serovars isolated
      from humans is 91. Twenty seven serovars from serogrup 0:4 (B); 23 serovars from
      serogrup 0:7 (C1); 25 serovars from serogrup 0:8 (C2-C3); 16 serovars from
      serogrup 0:9 (D1); 8 serovars from serogrup 0:3,10 (E1) and 5 serovars from
      serogrup 0:28 (M) have been reported. Only two of the more than 2600 serovars
      known were isolated firstly in Turkey: S. Istanbul (8:z10: e,n,x) in 1969 and S.
      Adana (43:z10:1,5) in 1977. Previously, serovars containing 1 and 25 O antigen of
      S. Boecker ([1],6,14,[25]) were isolated in 1967 and 1971 for the first time in
      Turkey. In 1967, a serovar containing T1 antigen that appears during S-R
      alteration in Salmonella, with (T1: b: e,n,x) antigen formula has been isolated
      from non-human samples and was reported to be a probable S-R alteration of
      Salmonella Benfica. Furthermore, non-motile isolates of Salmonella enterica subsp
      enterica serogrup 0:7 (C1) and serogrup 0:9 (D) were reported as well. While
      reporting a new Salmonella isolation in a country one should not be content with
      only giving the name of the serovar, but also emphasize the antigenic structure
      and the identification method clearly. 

PMID- 23971923
TI  - [BK virus infections in pediatric kidney transplant recipients].
AB  - Primary BK virus (BKV) infections acquired mainly during childhood are usually
      asymptomatic. Several studies revealed its seroprevalence in adult population as
      high as 90% worldwide. Following primary infection, virus persists as latent
      infection in the urogenital tract. In renal transplant recipients, primary
      infection and reactivations affect 10% of patients and without treatment, more
      than half of these patients lose their grafts. The only way of preventing graft
      loss due to BKV nephropathy (BKVN), seems to monitor BKV infection after
      transplantation and to diagnose patients developing BKVN during the early period
      and treat them accordingly. In this study, we analyzed BKV presence in plasma and
      urine samples with real-time PCR method and evaluated the renal biopsies of
      pediatric renal transplant recipients after transplantation, retrospectively. A
      total of 142 children (63 female, 79 male; mean age: 11.7 +/- 3.9 years) who had
      renal transplantation in Akdeniz University Medical Faculty, Antalya, Turkey,
      between February 2006 and April 2011 were enrolled in the study. After
      transplantation, peripheral blood and urine samples were collected bi-weekly for
      the first three months, monthly till the sixth month and every three months
      thereafter. BKV DNA was additionally screened in patients with unexplained rise
      in serum creatinine or in patients receiving anti-rejection therapy. In any
      plasma positivity or during the BKVN therapy, BKV DNA analysis was done bi
      weekly. After DNA extraction by automated system, an 83 base pair fragment in VP1
      region was amplified. Signal detection for the target region was performed with a
      TaqMan probe dual-labelled at the 5' end with 6-carboxyfluorescein (FAM) and the
      3' end with 6-carboxytetramethylrhodamine (TAMRA). Histopathological examinations
      of renal biopsies were done with routine histological stains and
      immunohistochemical staining with monoclonal antibodies directed to SV40 antigen.
      From 2171 plasma and 1995 urine samples without PCR inhibitors, 442 (20%) (range:
      300-4.5 x 10(7) copies/ml; mean: 2.0 x 10(5) +/- 2.2 x 10(6) copies/ml) and 800
      (40.1%) (range: 300-3 x 10(12) copies/ml; mean: 5.9 x 10(9) +/- 1.1 x 10(11)
      copies/ml) were found positive for BKV DNA, respectively. For 114 (80.3%)
      patients, at least one urine sample was positive and more than half of those
      patients (68/114, 59.6%) had viremia. Of the patients, 19.7% (28/142) had viral
      DNA above 10(4) copies/ml, which was choosen as a cut-off value for its high
      positive predictive value for BKVN. For all these 28 patients, prior to renal
      biopsy, immunosupressive treatment was decreased. Cidofovir and/or leflunomid
      were initiated to nine patients who did not respond to lowered immunosupressive
      therapy and eight of them had renal biopsy for the confirmation of BKVN. All
      renal biopsy results were compatible with BKVN. From these nine patients who were
      receiving cidofovir and/or leflunomid, two lost their grafts because of BKVN.
      Since viruria is frequently encountered and the viral load is usually in low
      quantities and transient, it is more appropriate to use blood samples for
      screening programmes after renal transplantation. The efficacy of antiviral
      treatment in BKVN could not be evaluated since it was only applied in patients
      non-responding to lowered immunosuppressive therapy and had decreased renal
      functions. Multicenter prospective studies are required to enlighten this
      important issue. Early diagnosis with close monitoring of renal function and
      viremia, seems to be the most effective way for controlling BKVN. 

PMID- 23971924
TI  - [Detection of resistance mutations in chronic hepatitis B patients receiving
      antiviral therapy for over one year].
AB  - Primary mutations conferring hepatitis B virus (HBV) antiviral resistance and
      associated secondary/compensatory mutations were investigated in this study by
      DNA sequencing (SEQ) and two commercial Line Probe Assays (LiPAs) (Inno-Lipa HBV
      DRv2 and Inno-Lipa HBV DRv3, Innogenetics, Belgium). A total of 71 subjects under
      follow-up for chronic hepatitis B and receiving lamivudine (LVD) therapy for one
      year or longer at the Hacettepe University Faculty of Medicine, Department of
      Internal Medicine, Gastroenterology Unit were included in the study with informed
      consent. Male to female ratio and mean age was noted as 47/24 and 43 +/- 15.8
      (age range: 13-71) years, respectively. Twenty samples with low HBV DNA levels
      (mean: 204.6 IU/ml) could not be interpreted by SEQ due to insufficient
      amplification. All samples with a positive consensus PCR were further analysed
      via LiPAs, as directed by the manufacturer. Thus a total of 51 and 56 samples
      could be evaluated via SEQ and LiPA assays, respectively. In 13 of the 51 (25.5%)
      samples by SEQ and in 9 of 56 (16%) samples by LiPAs, primary and compensatory
      mutations associated with resistance were identified. Multiple mutations that
      comprise L180M + M204I in four and L180M + M204V in one sample and single
      mutations (M204I) in three samples were identified by SEQ. In one sample which
      had multiple mutations associated with LVD resistance single mutations (S202G,
      N236T) associated with entecavir resistance and in two other such samples
      mutations associated with adefovir resistance were detected by SEQ. Also, in
      three samples amino acid substitution at position rt215 (QAES) as alone and in
      one sample with multiple mutations were observed via SEQ. In five of nine samples
      primary and compensatory multiple mutations (L180M + M204I in one sample, L80I +
      L180M + M204I in two samples, L80I/V + M204I in one sample) and primary single
      mutations associated with LVD resistance (M204I/V) in four samples were detected
      by Inno-Lipa HBV DRv2. Two different mutations (G202, ILFM184) were observed in
      two samples with multiple mutations associated LVD resistance via Inno-Lipa HBV
      DRv3. However, mutation at position rt184 was evaluated as a weak positive. Any
      mutation associated with adefovir resistance was not detected by LiPA. As a
      result, SEQ and LiPAs displayed comparable performances for the detection of HBV
      drug resistance mutations. We suggested that for the evaluation of discordant
      results, it should be better to test consecutive serum samples.

PMID- 23971925
TI  - [APOBEC3 hypermutations in HIV-1 infected cases in Turkey].
AB  - Host genetic factors may play an effective role on the human immunodeficiency
      virus (HIV) pathogenesis. APOBEC3 (apolipoprotein B mRNA editing enzyme catalytic
      polypeptide like-3) proteins are cellular antiviral proteins which inhibits HIV
      replication in the absence of vif (virion infectivity factor). In this study, we
      aimed to determine the APOBEC 3G/F hypermutations in HIV-1 strains isolated in
      Turkey. A total of 515 HIV-1 infected patients between June 2009 - February 2012
      were included in the study. Three hundred ninety four cases were newly diagnosed
      antiretroviral-naive patients [349 male, 45 female; median age (range): 37.1 (2
      69) years; median CD4+ T-cell count (range): 340 (1-1660) mm3; median HIV-RNA
      load (range): 5.76 + E5 (8.7 + E2-9.4 + E6) IU/ml] and 121 were under HAART
      therapy [99 male, 22 female; median age (range): 40.7 (20-70) years; median CD4+
      T-cell count (range): 195 (6-720) mm3; median HIV-RNA load (range): 5.4 + E5
      (1.37 + E3-1.07 + E7) IU/ml]. APOBEC 3G/F hypermutations in HIV-1 pol sequences
      (reverse transcriptase; codons 41-238 and protease; codons 1-99) analysed by
      nested RT-PCR and direct sequencing techniques. APOBEC 3G/F hypermutations have
      been determined by using of HIVdb-Stanford algorithm. The prevalence of overall
      APOBEC 3G/F hypermutations was 2.5% (13/515) in HIV-1 pol gene sequences in study
      group, and the rates were 2% (8/394) and 4.1% (5/121) in antiretroviral naive and
      treatment groups, respectively. However, the location and marker hypermutations
      of determined APOBEC in the HIV-1 pol gene sequences were RT and 3G in the
      Turkish patients. The hypermutated HIV-1 strains identified in HIV-1 infected
      patients may facilitate our understanding the nature and the consequences of HIV
      1 infections. Moreover, investigations of the motif and frequency of APOBEC 3G/F
      hypermutations in HIV-1 proviral DNA samples and understanding their
      relationships with HIV-1 subtypes in Turkish patients would be beneficial.

PMID- 23971926
TI  - [Investigation of HHV-8 prevalence in anti-HIV-1 positive patients in Istanbul,
      Turkey].
AB  - Human herpes virus-8 (HHV-8) infections are associated with Kaposi's Sarcoma
      (KS), Multiple Castleman disease and primary effusion lymphoma, and particularly
      important in HIV/AIDS and transplantation patients. The aim of this prospective
      study was to detect HHV-8 prevalence in HIV-1-infected patients,in a Turkish
      population. A total of 85 anti-HIV-1 positive patients (53 male, 32 female; age
      range: 1-70 years) diagnosed at Istanbul Faculty of Medicine, Infectious Diseases
      and Clinical Microbiology Department were included in the study. In 45 (53%) of
      the patients HIV-RNA was detectable and viral loads were between 20-10.000.000
      copies/ml. HHV-8-specific IgG antibodies were screened by using a commercial
      ELISA kit (Advanced Biotechnologies Inc, USA), and the presence of HHV-8 nucleic
      acids were investigated by PCR (Roche Diagnostics, Germany) in the blood samples
      obtained from patients. HHV-8 IgG was detected in 28.2% (24/85) of the anti-HIV-1
      positive patients, and HHV-8 DNA was detected in 3.5% (3/85). One of the three
      HHV-8 DNA positive cases was seropositive as well. Twenty-five percent of the
      seropositive patients were female (6/24) and 75% were male (18/24). Of three HHV
      8 DNA positive cases, two were male and one was female. The distribution of HHV-8
      seropositivity rates according to the age groups were as follows; 1/3 for 1-10
      years, 1/2 for 11-20 years, 3/8 for 21-30 years, 7/27 for 31-40 years, 9/30 for
      41-50 years, 1/9 for 51-60 years, and 2/6 for 61-70 years. The highest
      seropositivity rate was detected in 41-50 age group (9/24, 37.5%), followed by 31
      40 age group (7/24, 29.2%), presenting statistically significant differences
      between the other age groups (p< 0.05). HHV-8 DNA was detected in only 1 (4.2%)
      out of 24 IgG seropositive patients. HIV viral loads of the two HHV-8
      seronegative patients whose HHV-8 DNA levels of < 500 copy/ml, were < 20 copy/ml
      and 1250 copy/ml, respectively. HIV-RNA load of the other patient with HHV-8 IgG
      positivity and 2240 copy/ml of HHV-8 DNA, was 191.000 copy/ml. None of the HIV-1
      positive patients presented with clinical symptoms for KS. However, clinical and
      virological follow-up of those cases with HHV-8 IgG and/or DNA positivity would
      be useful to predict and control of a possible development of KS or other HHV-8
      related pathologies. For a more comprehensive understanding of HHV-8 epidemiology
      in Turkey, multicentre studies with higher number of cases are needed. 

PMID- 23971927
TI  - [Evaluation of fourteen adult cases with visceral leishmaniasis].
AB  - Visceral leishmaniasis is a life threatening systemic infectious disease caused
      by Leishmania protozoon, which is transmitted by phlebotomine sandflies, and is
      widespread in Mediterranean countries including Turkey. The aim of this study was
      to retrospectively evaluate the visceral leishmaniasis cases followed in our
      clinic between January 2005 to April 2012, under the light of the current
      literature. A total of 14 cases (7 female, 7 male; age range: 19-64 years, mean
      age: 41.6 +/- 12.9 years) diagnosed as visceral leishmaniasis and followed for
      one year after their treatment were included in the study. Data of the cases were
      obtained from the patient files. Ten of the cases were immunocompetent and four
      were immunosuppressive. While six of the cases were residents in Adana, eight
      were from different cities of south and southeastern Anatolia, Turkey. The median
      period between the development of symptoms and diagnosis was 75 (range: 2-272)
      days and 79% (11/14) of them were admitted to a health center and used
      antimicrobial agents. The leading presenting complaint was fever (100%) followed
      by chills and shiver (93%), weakness (71%) and weight loss (57%). Physical
      examination revealed fever in 8 (57%), splenomegaly in 11 (79%) and
      hepatosplenomegaly in 7 (50%) cases. Based on laboratory findings, pancytopenia
      was detected in 10 (71.4%) and hypoalbuminemia was detected in all (100%) of the
      cases. The diagnosis of visceral leishmaniasis was made by the detection of
      amastigote form of the parasite in the smears of bone marrow aspiration for 12
      (86%) cases and of tissue (liver/spleen) biopsies for two cases. Bone marrow
      samples obtained from all of the patients were inoculated into NNN (Novy-MacNeal
      Nicole) media and only 4 (29%) of them yielded the growth of Leishmania
      promastigots. Parenteral lipozomal amphotericin B was initiated to 10
      immunocompetent patients at a dose of 3 mg/kg/day and to three immunosuppressive
      patients at a dose of 4 mg/kg/day. One immunosuppressive patient lost his life
      before initiation of treatment. With regard to disease progression, it was
      detected that two cases (of whom one was renal and one was bone marrow transplant
      patient) lost their lives (mortality rate: 14%), however all the other cases were
      cured completely. The present study comprised the highest number of visceral
      leishmaniasis adult cases reported in Turkey and enabled the review of disease
      characteristics. In conclusion, cases presenting with fever, hepatosplenomegaly,
      pancytopenia and hypoalbuminemia and living in endemic regions should be
      precisely evaluated in terms of visceral leishmaniasis. 

PMID- 23971928
TI  - [Seroepidemiology of pertussis in 10-15 years old healthy children in Isparta
      province, Turkey].
AB  - Pertussis, a highly contagious respiratory disease, commonly affects infants and
      young children and can be fatal, especially in babies less than one year of age.
      Bordetella pertussis continues to circulate even in populations where a high
      vaccine coverage of infants and children is achieved. Adults are reservoirs for
      infections in infants, in whom pertussis may be severe and life-threatening.
      Despite the rising rates of vaccination in our country and all over the world for
      the past 25 years, the number of pertussis cases among adolescents and adults has
      been increasing. To decrease the risk of pertussis infection and thus protect
      adults and adolescents against pertussis, booster doses should be administered to
      preschool children and adolescents. In order to decide when to administer the
      booster doses in a country, age-specific seropidemiology of the disease should be
      known. The aim of this study was to determine the pertussis toxin antibody levels
      of fully vaccinated healthy children in Isparta, Turkey, aged 10-15 years old. A
      total of 296 participants, that comprised fully vaccinated 254 healthy elementary
      school students aged between 10-15 years (126 male, 128 female) and 42 adults
      between 18-39 years old (21 male, 21 female) were included in the study with
      informed consent. The sensitivities of subjects to pertussis were tested by the
      determination of pertussis toxin IgG levels with the use of commercial ELISA test
      (Genzyme Virotech, Germany). In our study, the seropositivity rate was found
      12.6% (32/254) for 10-15 age group, however all the adult subjects were
      seronegative. Thus the total seropositivity rate was estimated as 10.8% (32/296).
      Pertussis toxin IgG seropositivity rate was 12.7% (16/126) for males and 12.5%
      (16/128) for females, and there was no significant gender difference (p> 0.05).
      The highest seropositivity rates were detected at 10(th) (23.8%) and 11(th) (19%)
      years in males, and 12(th) and 14(th) (23.8%) years in females. No seropositivity
      was detected in individuals over age 15 in our study. Since adults lose their
      immune protection gained by pertussis vaccination, they start becoming an
      infection source for infants. Therefore, a booster dose of acellular pertussis
      vaccine should be considered in preschool period and at ages 14-18. Further
      studies regarding diagnosis and surveillance of pertussis disease are required,
      as well as enhancement of vaccination rates. 

PMID- 23971929
TI  - [Development of a novel Francisella tularensis antigen stained with tetrazolium
      blue for tularemia microagglutination test].
AB  - The isolation of Francisella tularensis in cultures is the reference method for
      the laboratory diagnosis of tularemia. However, due to the limitations such as
      the low sensitivity and need for high safety level and equipped laboratories,
      serologic methods are frequently used as diagnostic tools. F.tularensis-specific
      antibodies may be demonstrated by several methods, however microagglutination
      test (MA) remains the most common method with its high sensitivity and
      specificity. The aim of this study was to develop a novel MA test antigen
      prepared from whole F.tularensis cells and stained with tetrazolium-blue for more
      clear and easier evaluation. F.tularensis NCTC 10857 strain was cultured on the
      cysteine heart agar supplemented with 9% sheep blood and bacterial cells were
      harvested by scraping, collected in physiological saline (PS) and centrifuged at
      1500 rpm for 10 minutes. For preparing stock antigen suspension cell
      concentration was adjusted to OD600=1.5, spectrophotometrically. Tetrazolium-blue
      solution (BTC [3,3'-(3,3'-Dimethoxy[1,1'-biphenyl]-4,4'-diyl) bis [2,5-diphenyl
      2H-tetrazolium dichloride], T4375 Sigma-Aldrich) at the final concentration of 1%
      was added to cell suspension and incubated at 37 degrees C for 5 hours for
      absorption. Then, the living cells were chemically inactivated by formaldehyde.
      Repeating centrifugations were performed to discard excess dye and formaline,
      then 0.4% formaline saline was added on the sediment. Optimum concentration of
      this novel antigen (BTC-Ag) for MA test was determined by plate titration method
      by using standard serum sample with a known MA titer (1/128). The performance of
      BTC-Ag in MA test was evaluated by using 100 patient sera positive for
      F.tularensis antibodies, and 100 tularemia negative patient sera (of them 50 were
      seropositive for brucellosis). All of the results were compared with standard MA
      test in which safranin-O stained antigen (SO-Ag) was used. There was 100%
      agreement between the two tests performed with BTC-Ag and SO-Ag in tularemia
      seropositive (in >= 1/20 titers and when +/-1 dilution variation was accepted as
      normal) and seronegative sera. No significant cross reactivity with Brucella spp.
      was observed. Accuracy, sensitivity and specificity of BTC-Ag were found to be
      100%. In conclusion, newly developed BTC-Ag for MA test provides better
      agglutination patterns resulting in a clear supernatant in wells, thus provides
      easy evaluation for the agglutination reaction, and is expected to facilitate
      tularemia serodiagnosis. 

PMID- 23971930
TI  - [Comparison of in vitro antimicrobial activities of bioaggregate and mineral
      trioxide aggregate].
AB  - Treatment outcome of endodontic perforations depends on successful elimination of
      the associated microorganisms and infected tissues as well as the effective seal
      of the root-end or perforation site to prevent future contamination. Ideally,
      perforation repair material has to be bacteriostatic or bactericidal in order to
      prevent bacterial contamination as well as good sealing properties and
      biocompatibility. The aim of this study was to evaluate the antimicrobial effects
      of BioAggregate (BA) and Mineral Trioxide Aggregate (MTA) on the standard strains
      of Candida albicans, Enterococcus faecalis, Escherichia coli, Streptococcus
      mutans, Streptococcus sanguinis and Pseudomonas aeruginosa using the agar disc
      diffusion test. Colonies of each strains were harvested from the medium and
      microorganisms were diluted to obtain a suspension of approximately 108 cfu/ml.
      Petri plates with blood agar base with 5% sheep blood or Sabouraud dextrose agar
      (for C.albicans) were inoculated with experimental suspensions and BA and MTA
      discs prepared as 2 mm length and 6 mm diameter were placed. After 24 and 48
      hours incubation, the diameters of the zones of inhibition were measured. The
      results of the disc diffusion tests showed that BA and MTA were effective on the
      tested microorganisms at 24 and 48 hours incubation periods. BA and MTA showed
      similar antimicrobial effects on C.albicans and E.coli. BA was more effective
      than MTA on S.mutans, E.faecalis and P.aeruginosa, however MTA was more effective
      than BA on S.sanguinis at 48 hours. When the time efficiency of the materials
      were compared, there was no statistically difference between 24 to 48 hours on
      E.coli, E.faecalis, S.mutans, S.sanguinis in both two groups (p> 0.05). There was
      statistically significant decrease 24 to 48 hours on C.albicans in BA and MTA
      groups and P.aeruginosa in BA group (p< 0.05). It can be concluded that although
      BA and MTA displayed similar antimicrobial efficacy on the tested microorganisms
      newly improved material BA demonstrated superior antimicrobial activity than
      other. 

PMID- 23971931
TI  - [A severe cutaneous anthrax case complicated with sepsis in Bursa, Turkey].
AB  - Anthrax is a zoonotic infection caused by Bacillus anthracis. Although the
      incidence of disease has been decreasing in Turkey, it is still endemic in some
      regions of the country. The cutaneous form of disease is the most common clinical
      form, usually benign and rarely causes bacteriemia and sepsis. In this report, a
      case of cutaneous anthrax complicated with sepsis where B.anthracis was isolated
      from blood and wound cultures, was presented. A 53-years-old male living in Bursa
      province (northwestern Turkey), admitted to the emergency ward with high fever
      and a lesion on the right arm. His history indicated that he is dealing with
      livestock breeding and injured his arm during slaughtering of a sick lamb. The
      infection started as a black colored painless ulcer with 2 cm in diameter on his
      right elbow. The case was hospitalized and penicillin G therapy was started with
      the preliminary diagnosis of anthrax. Bullous lesions occurred around the wound,
      got necrosis and integrated with the first lesion. Gram stained slides from the
      bullous lesions revealed capsulated gram-positive bacilli under light microscope.
      Gram-positive bacilli were also isolated from bullous lesions and the blood
      cultures. The isolates were identified and confirmed as B.anthracis by
      conventional and molecular methods. Antibiotic susceptibility tests were
      performed by E-test method and the isolates were found to be susceptible to
      ampicillin, tetracyclin, tigecyclin, ciprofloxacin, levofloxacin, gentamycin,
      chloramphenicol, erythromycin, clarithromycin, vancomycin, linezolid, daptomycin
      and rifampicin. The lesion became surrounded by an extensive erythema and edema
      and expanded to the whole arm. Moxifloxacin was initiated due to the fact that
      clinical progress. During the second week of the therapy, a black colored scar
      was observed on the wound while hyperemia and edema regressed. The necrotic
      tissue debridated to accelerate healing and rest of the skin defect was planned
      for reconstruction. The patient who had septicaemia and disseminated cellulitis
      was discharged after his treatment continued for 14 days. Multiple-locus variable
      number tandem repeat analysis method was used for molecular epidemiological
      investigation. The strains isolated from the patient were identified as genotype
      (GK) 43 classified in A3.a major cluster, and found to be identical to those
      strains isolated from animals in different provinces located at central and
      eastern Anatolia of Turkey. In conclusion, the risk of sepsis must be considered
      in patients with cutaneous anthrax with appropriate follow-up and treatment plan.

PMID- 23971932
TI  - [Four cases of cutaneous anthrax in Diyarbakir, Turkey].
AB  - Anthrax which is a rare disease in developed countries, is still a serious public
      health problem in countries like Turkey where livestock is common. In this
      report, four cases of cutaneous anthrax detected in Kirkira village of
      Diyarbakir, Southeast Anatolia, Turkey, were presented. Three female and one male
      patients were admitted to our hospital with the complaints of skin lesions and
      high fever lasting for 10 days. Their history indicated that they injured their
      fingers during slaughtering of a dead cow meat. All patients had irregular edged
      necrotic vesiculobullous lesions on the erythematous and edematous base on their
      hand fingers, developed in 1 week following the contact. There was no systemic
      finding and the laboratory findings were within normal limits. Typical bamboo
      cane shaped gram-positive bacilli were observed on the Gram stained smears
      prepared from the vesicular lesions. Aerobic cultures in blood agar media
      revealed typical R type colonies, gray in color, creased, granulated and 2-3 mm
      in diameter within 24 hours of incubation. In one patient although the lesion was
      typical and characteristic gram-positive bacilli were detected in the Gram
      stained smears, no growth was seen in the cultures. The isolates (n= 3) were
      identified as Bacillus anthracis by conventional microbiological methods, and
      also confirmed by Vitek 2 (BioMerieux, France) automated identification system.
      Antibiotic susceptibility tests were performed by disc diffusion method according
      to the CLSI guidelines. The isolates were found susceptible to penicillin G,
      ampicillin, erythromycin, amikacin, chloramphenicol, tetracycline, vancomycin and
      ciprofloxacin. All of the patients were treated successfully with penicillin or
      ciprofloxacin accompanied by topical wound care. In the last years several case
      series of anthrax were reported especially from the East and Southeastern
      Anatolia regions of Turkey. These four cutaneous anthrax cases from Diyarbakir,
      Turkey were reported to withdraw attention to anthrax in that specific area. It
      was concluded that in areas where anthrax is endemic to educate people under
      risk, to take the necessary preventive measures and to rule out anthrax in the
      differential diagnosis of cases presenting with typical ulcers and had contact
      with animals or their products, are of crucial importance for the early
      initiation of appropriate treatment which would decrease related morbidity and
      mortality. 

PMID- 23971933
TI  - [HBV vaccine escape mutations in a chronic hepatitis B patient treated with
      nucleos(t)ide analogues].
AB  - The hepatitis B virus (HBV) polymerase (pol) gene completely overlaps with the
      envelope (S) gene. Nucleos(t)ide analogue (NA) resistance mutations in the pol
      gene of HBV, either from selection of primary or secondary resistance mutations,
      typically result in changes in the overlapping hepatitis B surface antigen
      (HBsAg). Recent studies have conferred a new acronym to these HBV pol/S gene
      overlap mutants; ADAPVEMs, for antiviral drug-associated potential vaccine-escape
      mutants. The present report aimed to assess the determined multiple HBV vaccine
      escape mutants in a Turkish patient with chronic hepatitis B (CHB), undergoing
      NAs treatment. The liver biopsy of HBsAg positive, HBeAg negative 53-year old
      female patient with CHB, revealed a score as histological activity index; 9 and
      fibrosis; 2 according to Ishak classification. NA treatment backgrounds consisted
      of 24 months lamivudine, followed by 18 months entacavir and lastly 3 months
      tenofovir monotherapies. Since HBV DNA load was determined as 7.030.000 IU/ml at
      the 4th month of tenofovir therapy, entecavir was added as current treatment
      regimen, and tenofovir + entecavir therapy decreased the HBV DNA load (400
      IU/ml). Sequence analysis was performed for HBV pol/S gene and overlapping pol/S
      gene amino acid substitutions, primary/compensatory NA resistance mutations and
      antiviral drug-associated potential vaccine-escape mutations (ADAPVEM) were
      analysed. The patient isolate was identified as genotype D/subgenotype D1 of HBV.
      Primary drug resistance mutations (rtV173L + rtL180M + rtM204V) to lamivudine and
      telbivudine and a compensatory mutation (rtQ215H) to lamivudine and adefovir were
      described in the HBV pol gene sequence. However, multiple HBV vaccine-escape
      mutations (sS143T + sD144E + sG145R + sE164D + sI195M) have been determined on
      the HBV overlapping pol/S gene region. Lamivudine and telbivudine which are the
      frequently preferred drugs for the treatment of CHB in Turkey, have the potential
      to lead to ADAPVEMs. Thus ADAPVEMs should be monitored in infected and NA treated
      CHB patients and their public health risks should be assessed. 

PMID- 23971934
TI  - [First case of hepatitis B virus genotype H infection in Turkey].
AB  - Clinical studies reported from Turkey indicate that hepatitis B virus (HBV)
      genotype D is more prevalent than other genotypes. Epidemiological and clinical
      information on genotype H infection is currently limited. Genotype H infection is
      most likely due to its regional (Central and South America) prevalence throughout
      the world. The aim of this report is to present the first HBV genotype H
      infection in a chronic hepatitis B patient in Turkey. Laboratory findings of a 42
      years old male patient admitted to our hospital revealed HBsAg (+), anti-HBs (-),
      HBeAg (-), anti-HBe (+), anti-HBc IgM (-), anti-HBc IgG (+), anti-HAV IgG (+),
      HBV-DNA: 5.689.776 IU/ml and high liver enzymes (ALT: 223 U/L, AST: 121 U/L).
      History of the patient indicated no risk factor (intravenous drug use, blood
      transfusion, suspicious sexual contact) related to HBV transmission. Since liver
      ultrasonography showed multiple hemangiomas, biopsy was performed and histologic
      activity index was found as 6/18 and fibrosis as 2/6, according to modified
      Knodell score system. HBV DNA isolated from the serum sample of the patient was
      amplified by polymerase chain reaction and polymerase gene segment of HBV was
      directly sequenced. UPGMA method was used for phylogenetic analysis, and the
      genotype of the virus was identified accordingly. The nucleotide sequence was
      compared to those from the international DNA data bank (GenBank). The genotyping
      of the patient revealed that the isolated HBV was genotype H. Treatment with
      tenofovir disoproxil fumarate was initiated and the patient responded to the
      treatment. This finding suggested that other HBV genotypes, except the
      predominant genotype D may also be in circulation in Turkey. In conclusion,
      detection of epidemiologic and molecular characteristics of HBV genotype H which
      is related to chronic hepatitis, seems to be necessary in order to better
      understand its circulation and progression around the world. 

PMID- 23971935
TI  - [Clostridium difficile infection: epidemiology, risk factors, pathogenesis,
      clinical features, diagnosis and therapy].
AB  - Clostridium difficile is a gram-positive, spore-forming anaerobic bacterium.
      C.difficile is the leading cause of antibiotic associated diarrhea and colitis.
      The clinical spectrum of C.difficile infection (CDI) is highly variable, ranging
      from mild diarrhea to severe forms of intestinal illness including toxic
      megacolon, ileus, bowel perforation, and pseudomembranous colitis. Advanced age,
      long duration of hospitalization, and exposure to certain antimicrobial agents
      are the most common risk factors for CDI. The main virulence determinants of
      C.difficile are toxin A (enterotoxin) and toxin B (cytotoxin). Diagnosis of CDI
      is based on the identification of C.difficile toxin A or B in diarrheal stool.
      Various laboratory tests have been currently developed for the detection of
      C.difficile or its toxins in stool samples. The cell culture cytotoxicity assay
      and toxigenic culture have been regarded as the reference standard methods for
      the detection of C.difficile toxins. However, both of the reference methods are
      laborious, time consuming, and need expert personnel. Therefore, many
      microbiology laboratories use enzyme immunoassays, glutamate dehydrogenase
      antigen tests and real-time polymerase chain reaction (PCR) which are more rapid
      and practical. First-line antibiotics for CDI treatment are metronidazole and
      vancomycin. In this review, epidemiology, clinical spectrum, risk factors,
      pathogenesis, diagnostic methods and treatment of CDI have been summarized. 

PMID- 23971936
TI  - [Role of line immunoassay in the diagnosis of early HIV infection: a diagnostic
      case].
AB  - Combined p24 antigen-HIV antibody fourth-generation assays that identify most of
      the early HIV infections have been used extensively worldwide for several years.
      This poses challenges for the traditional algorithm of line immunoassay (LIA)
      confirmation. LIA tests are useful methods with their high specificity and their
      ability to differentiate HIV-1 from HIV-2, but they are reactive days after the
      fourth generation enzyme immunoassays. With acute HIV infection, high levels of
      infectious virus are detectable in serum and genital secretions. The rate of
      transmission during acute HIV infection is higher than the established HIV
      infection, for this reason, new HIV testing strategies need to focus on
      sensitivity, especially for this highly contagious phase immediately after
      infection. Serum sample of a patient sent to Ege University Hospital Clinical
      Virology Laboratory was repeatedly reactive with low signal/cutoff ratios with
      two different commercial fourth generation enzyme immunoassays (Architect HIV
      Ag/Ab Combo Reagent Kit, Abbott, Germany and Vidas HIV Duo Quick, Biomerieux,
      France). The sample was non-reactive with the LIA (INNO-LIA HIV I/II Score,
      Innogenetics, Belgium) and HIV RNA (RealTime HIV-I Amplification Reagent Kit,
      Abbott, USA) result was positive (4.1 x 10(5) copies/ml). With the presentation
      of this case, the role of LIA in the diagnosis of early HIV infection and its
      place in test algorithms were questioned. 

PMID- 23971937
TI  - Topography-based surface tension gradients to facilitate water droplet movement
      on laser-etched copper substrates.
AB  - This paper describes a method for creating a topography-based gradient on a
      metallic surface to help mitigate problems associated with condensate retention.
      The gradient was designed to promote water droplet migration toward a specified
      region on the surface which would serve as the primary conduit for drainage using
      only the roughness of the surface to facilitate the movement of the droplets. In
      this work, parallel microchannels having a fixed land width but variable spacing
      were etched into copper substrates to create a surface tension gradient along the
      surface of the copper. The surfaces were fabricated using a 355 nm Nd:YVO4 laser
      system and then characterized using spray testing techniques and water droplet (2
      10 MUL) injection via microsyringe. The distances that individual droplets
      traveled on the gradient surface were also measured using a goniometer and CCD
      camera and were found to be between 0.5 and 1.5 mm for surfaces in a horizontal
      orientation. Droplet movement was spontaneous and did not require the use of
      chemical coatings. The theoretical design and construction of surface tension
      gradients were also explored in this work by calculating the minimum gradient
      needed for droplet movement on a horizontal surface using Wenzel's model of
      wetting. The results of this study suggest that microstructural patterning could
      be used to help reduce condensate retention on metallic fins such as those used
      in heat exchangers in heating, ventilation, air-conditioning, and refrigeration
      (HVAC&R) applications. 

PMID- 23971938
TI  - New proposal for the serum ascites albumin gradient cut-off value in Chinese
      ascitic patients.
AB  - BACKGROUND: Serum ascites albumin gradient (SAAG) has been recognized as a
      reliable marker in the differential diagnosis of ascites. The etiological
      background of cirrhosis is rather different between western countries and eastern
      countries. The threshold of SAAG in Chinese ascitic patients has not been
      evaluated yet. The aim of this study was to define a new reasonable threshold of
      SAAG in Chinese ascitic patients. METHODS: Adult patients with ascites admitted
      to the Shanghai Changzheng Hospital from Jan 2004 to Jun 2010 were
      retrospectively analyzed. The diagnostic criteria for cirrhotic ascites are
      clinical manifestations, radiological features and esophageal-gastric varicosis,
      or histopathology. Serum was detected by chemical method using a commercial kit.
      We used receiver operating characteristic (ROC) analysis to achieve maximal
      sensitivity and specificity of SAAG. RESULTS: The mean value of SAAG in portal
      hypertension-related ascites was significantly higher than that in the non-portal
      hypertension-related ascites (21.15 +/- 4.38 g/L vs 7.48 +/- 3.64 g/L, P =
      0.002). The SAAG cut-off value under 12.50 g/L predicted portal hypertension
      ascites with the sensitivity of 99.20%, specificity of 95.10% and accuracy of
      97.65%. CONCLUSIONS: SAAG is useful to distinguish portal-hypertension-related
      ascites and non-portal-hypertension-related ascites, and 12.50 g/L might present
      as a more reasonable threshold in Chinese ascitic patients. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1602582638991860.

PMID- 23971939
TI  - IRF5, but not TLR4, DEFB1, or VDR, is associated with the risk of ulcerative
      colitis in a Han Chinese population.
AB  - OBJECTIVE. IRF5, TLR4, DEFB1, and VDR genetic variations have been associated
      with ulcerative colitis (UC) in several European patient cohorts. As distinct
      genetic backgrounds may play a role in different ethnicities, we evaluated the
      effects of single-nucleotide polymorphisms (SNPs) in these genes and their
      interactions in UC patients of Han Chinese descent. MATERIAL AND METHODS. DNA
      samples from 300 UC patients and 302 healthy control subjects from Peking Union
      Medical College Hospital were genotyped for 14 tag SNPs, which were selected
      based on haplotype analysis of IRF5, TLR4, DEFB1, and VDR. Multidimensionality
      reductions were used to explore gene-gene interactions. RESULTS. The only
      observed association with UC was for IRF5. On an allelic level, SNP rs3807306 was
      associated with UC risk (p = 6.7 * 10(-3)). On a genotypic level, the CC genotype
      of SNP rs3807306 (p = 0.03) was associated with protection from UC, and the AA
      genotype of SNP rs4728142 (p = 7.6 * 10(-3)) was associated with a risk of UC. In
      the haplotype analysis, GGATT was highly correlated with UC risk (p-Value = 2.0 *
      10(-4)). No significant multilocus interactions were detected among these four
      genes. CONCLUSIONS. Our study confirmed the association of IRF5 with UC in Han
      Chinese patients. Han Chinese UC patients share part of their genetic
      susceptibility with Caucasian patients.

PMID- 23971940
TI  - Obstetric management does not influence vertical transmission of HCV infection:
      results of the ALHICE group study.
AB  - OBJECTIVE: To investigate the impact of variation in obstetric practice during
      labor and childbirth upon the rate of neonatal transmission of HCV. METHODS:
      Pregnant mothers were included in this prospective study from six hospitals in
      Southern France on the basis of positive HCV serology. Data recorded for the
      study included maternal factors, delivery details and laboratory data concerning
      mother and child. Pediatric follow-up was documented for a minimum of 1 year and
      for up to 2 years for children with circulating HCV RNA. RESULTS: Two hundred and
      fourteen mother-child pairs were investigated. HIV/HCV co-infected mothers had a
      rate of HCV transmission significantly higher (11%) than that observed for mono
      infected mothers (3.8%) (odds ratio=3.08 [95% CI:0.95 to 9.99] p=0.05). When the
      HCV viral load was greater than or equal to 6 log copies/ml, the transmission
      rate was 14.3% [95% CI:5.4-28.5], this representing a risk of transmission four
      times higher than for women with a lower viral load (OR=4 [95% CI:1.3-12.4]).
      Among co-infected mothers, the risk of transmission was significantly increased
      even when the load was less than 6 log copies/ml (p=0.006). Risk factors were
      identified related to labor (duration and induction type); the birth process
      (rupture of the amniotic sac, complete opening of the sac, appearance of the
      amniotic fluid); fetal characteristics (prematurity) and obstetric maneuvers
      (instrumental extractions, spontaneous or induced perineal trauma) and none of
      these factors were associated with an increased rate of HCV maternal-fetal
      transmission. CONCLUSIONS: HCV infection does not appear to be a legitimate
      indication for modifying obstetric practices with regards to type of induction,
      monitoring of labor, route of delivery, fetal and perineal obstetric maneuvers or
      care of the newborn in the delivery room.

PMID- 23971941
TI  - Virological and immunological response to antiretroviral regimens containing
      maraviroc in HIV type 1-infected patients in clinical practice: role of different
      tropism testing results and of concomitant treatments.
AB  - We assessed the immunovirological response to antiretroviral regimens containing
      maraviroc in HIV-infected viremic patients with viral tropism predicted by
      different assays. We selected antiretroviral treatment-experienced HIV-1-infected
      patients initiating regimens containing maraviroc after different phenotypic or
      genotypic viral tropism assays, with at least one HIV-1 RNA determination during
      follow-up. Survival analysis was employed to assess the virological response as
      time to HIV-1 RNA <50 copies/ml and immunological response as time to a CD4 cell
      count increase of >= 100/MUl from baseline. Predictors of these outcomes were
      analyzed by multivariate Cox regression models. In 191 treatments with maraviroc,
      virological response was achieved in 65.4% and the response was modestly
      influenced by the baseline viral load and concomitant drug activity but not
      influenced by the type of tropism assay employed. Immunological response was
      achieved in 58.1%; independent predictors were baseline HIV-1 RNA (per log10
      higher: HR 1.29, 95% CI 1.05-1.60) and concomitant therapy with enfuvirtide (HR
      2.05, 0.96-4.39) but not tropism assay results. Of 17 patients with baseline R5
      tropic virus and available tropism results while viremic during follow-up on
      maraviroc, seven (41%) showed a tropism switch to non-R5 virus. A significant
      proportion of experienced patients treated with regimens containing maraviroc
      achieved virological response. The tropism test type used was not associated with
      immunovirological response and concomitant treatment with enfuvirtide increased
      the chance of immunological response. More than half of virological failures with
      maraviroc were not accompanied by tropism switch.

PMID- 23971943
TI  - Complementarity between in silico and biophysical screening approaches in
      fragment-based lead discovery against the A(2A) adenosine receptor.
AB  - Fragment-based lead discovery (FBLD) is becoming an increasingly important method
      in drug development. We have explored the potential to complement NMR-based
      biophysical screening of chemical libraries with molecular docking in FBLD
      against the A(2A) adenosine receptor (A(2A)AR), a drug target for inflammation
      and Parkinson's disease. Prior to an NMR-based screen of a fragment library
      against the A(2A)AR, molecular docking against a crystal structure was used to
      rank the same set of molecules by their predicted affinities. Molecular docking
      was able to predict four out of the five orthosteric ligands discovered by NMR
      among the top 5% of the ranked library, suggesting that structure-based methods
      could be used to prioritize among primary hits from biophysical screens. In
      addition, three fragments that were top-ranked by molecular docking, but had not
      been picked up by the NMR-based method, were demonstrated to be A(2A)AR ligands.
      While biophysical approaches for fragment screening are typically limited to a
      few thousand compounds, the docking screen was extended to include 328,000
      commercially available fragments. Twenty-two top-ranked compounds were tested in
      radioligand binding assays, and 14 of these were A(2A)AR ligands with K(i) values
      ranging from 2 to 240 MUM. Optimization of fragments was guided by molecular
      dynamics simulations and free energy calculations. The results illuminate
      strengths and weaknesses of molecular docking and demonstrate that this method
      can serve as a valuable complementary tool to biophysical screening in FBLD.

PMID- 23971942
TI  - Postnatal exposure to methyl mercury and neuropsychological development in 7-year
      old urban inner-city children exposed to lead in the United States.
AB  - BACKGROUND: The most common route for general population exposure to methyl
      mercury (MeHg) is fish consumption. Recommendations to pregnant women about
      consuming fish contaminated with MeHg are also applied to children, but there are
      few studies available about the effects of low-level postnatal MeHg exposure in
      them. OBJECTIVES: To investigate the association between postnatal methyl mercury
      exposure and neuropsychological development in a study of children also exposed
      to lead, both measured at 7 years. METHODS: We measured MeHg concentrations in
      blood samples from the Treatment of Lead-Exposed Children (TLC) trial in which
      780 children with elevated concentrations of lead in blood were followed with
      neuropsychological tests from ages 12-33 months through 7 years. Here we examine
      blood MeHg concentration and neuropsychological test scores, both measured at age
      7 years. We used a maximum likelihood method to estimate geometric mean MeHg
      concentration and generalized linear regression models to analyze MeHg and
      neuropsychological test scores. RESULTS: Geometric mean MeHg concentration was
      0.56 (95% confidence interval: 0.52, 0.59) MU g/L. A 1  MU g/L increase in MeHg
      was associated with a 2.1 (95% confidence interval: 0.4, 3.8) point increase in
      Full-Scale IQ and 0.2 (95% confidence interval: 0.02, 0.4) point increase in
      Learning Slopeindex T-score on a test of verbal memory. CONCLUSIONS: Our results
      suggest that the relatively low MeHg exposure in US school-aged children from
      this population has no detectable adverse effect on neuropsychological
      development. The positive associations observed between MeHg and neurodevelopment
      may indirectly reflect consumption of beneficial polyunsaturated fatty acids from
      seafood.

PMID- 23971944
TI  - Analyzing the impact of social factors on homelessness: a fuzzy cognitive map
      approach.
AB  - BACKGROUND: The forces which affect homelessness are complex and often
      interactive in nature. Social forces such as addictions, family breakdown, and
      mental illness are compounded by structural forces such as lack of available low
      cost housing, poor economic conditions, and insufficient mental health services.
      Together these factors impact levels of homelessness through their dynamic
      relations. Historic models, which are static in nature, have only been marginally
      successful in capturing these relationships. METHODS: Fuzzy Logic (FL) and fuzzy
      cognitive maps (FCMs) are particularly suited to the modeling of complex social
      problems, such as homelessness, due to their inherent ability to model intricate,
      interactive systems often described in vague conceptual terms and then organize
      them into a specific, concrete form (i.e., the FCM) which can be readily
      understood by social scientists and others. Using FL we converted information,
      taken from recently published, peer reviewed articles, for a select group of
      factors related to homelessness and then calculated the strength of influence
      (weights) for pairs of factors. We then used these weighted relationships in a
      FCM to test the effects of increasing or decreasing individual or groups of
      factors. Results of these trials were explainable according to current empirical
      knowledge related to homelessness. RESULTS: Prior graphic maps of homelessness
      have been of limited use due to the dynamic nature of the concepts related to
      homelessness. The FCM technique captures greater degrees of dynamism and
      complexity than static models, allowing relevant concepts to be manipulated and
      interacted. This, in turn, allows for a much more realistic picture of
      homelessness. Through network analysis of the FCM we determined that Education
      exerts the greatest force in the model and hence impacts the dynamism and
      complexity of a social problem such as homelessness. CONCLUSIONS: The FCM built
      to model the complex social system of homelessness reasonably represented reality
      for the sample scenarios created. This confirmed that the model worked and that a
      search of peer reviewed, academic literature is a reasonable foundation upon
      which to build the model. Further, it was determined that the direction and
      strengths of relationships between concepts included in this map are a reasonable
      approximation of their action in reality. However, dynamic models are not without
      their limitations and must be acknowledged as inherently exploratory.

PMID- 23971945
TI  - Toward an understanding of the retinal chromophore in rhodopsin mimics.
AB  - Recently, a rhodopsin protein mimic was constructed by combining mutants of the
      cellular retinoic acid binding protein II (CRABPII) with an all-trans retinal
      chromophore. Here, we present a combined computational quantum
      mechanics/molecular mechanics (QM/MM) and experimental ultrafast kinetic study of
      CRABPII. We employ the QM/MM models to study the absorption (lambda(a)max),
      fluorescence (lambda(f)max), and reactivity of a CRABPII triple mutant
      incorporating the all-trans protonated chromophore (PSB-KLE-CRABPII). We also
      study the spectroscopy of the same mutant incorporating the unprotonated
      chromophore and of another double mutant incorporating the neutral unbound
      retinal molecule held inside the pocket. Finally, for PSB-KLE-CRABPII, stationary
      fluorescence spectroscopy and ultrafast transient absorption spectroscopy
      resolved two different evolving excited state populations which were
      computationally assigned to distinct locally excited and charge-transfer species.
      This last species is shown to evolve along reaction paths describing a facile
      isomerization of the biologically relevant 11-cis and 13-cis double bonds. This
      work represents a first exploratory attempt to model and study these artificial
      protein systems. It also indicates directions for improving the QM/MM models so
      that they could be more effectively used to assist the bottom-up design of
      genetically encodable probes and actuators employing the retinal chromophore. 

PMID- 23971946
TI  - 'I understand all the major things': how older people with limited English
      proficiency decide their need for a professional interpreter during health care
      after stroke.
AB  - OBJECTIVE: To explore the process of decision-making of older people with limited
      English proficiency (LEP) about using a professional interpreter during their
      health care after stroke. DESIGN: A constructivist grounded theory approach was
      used. Up to two in-depth interviews were conducted with 13 older people with LEP
      from seven different language groups, and one older person who preferred to speak
      English, who had recently received health care after an acute stroke.
      Professional interpreters assisted with 19 of the 24 study interviews. Data were
      analysed and theoretical processes developed using a constant comparative method.
      RESULTS: Professional interpreters were not a strong presence in the health care
      experience after stroke for participants. The use of professional interpreters
      was a complex decision for participants, influenced by their perception of the
      language and health care expertise of themselves and others, their perceived
      position to make the decision and whom they trusted. Getting by in English
      allowed participants to follow rules-based talk of health professionals, but did
      not enable them to understand detailed information or explanation, or to engage
      in the management of their condition in a meaningful way. CONCLUSION: Health
      professionals have an opportunity and a mandate to demonstrate leadership in the
      interpreter decision by providing knowledge, opportunity and encouragement for
      people with LEP, to use an interpreter to engage in, and understand, their health
      care after stroke. Health professionals may need to advise when interpretation is
      needed for health care situations, when communication difficulties may not be
      anticipated by the person with LEP.

PMID- 23971948
TI  - Exceptional steric congestion in an in,in-bis(hydrosilane).
AB  - The synthesis and characterization of a macrobicyclic in,in-bis(hydrosilane) is
      described. A combination of crystallographic and computational data indicate that
      the central hydrogen-hydrogen nonbonded contact distance is the shortest for any
      crystallographically characterized compound. 

PMID- 23971947
TI  - Estrogen receptor negative/progesterone receptor positive breast cancer is not a
      reproducible subtype.
AB  - INTRODUCTION: Estrogen receptor (ER) and progesterone receptor (PR) testing are
      performed in the evaluation of breast cancer. While the clinical utility of ER as
      a predictive biomarker to identify patients likely to benefit from hormonal
      therapy is well-established, the added value of PR is less well-defined. The
      primary goals of our study were to assess the distribution, inter-assay
      reproducibility, and prognostic significance of breast cancer subtypes defined by
      patterns of ER and PR expression. METHODS: We integrated gene expression
      microarray (GEM) and clinico-pathologic data from 20 published studies to
      determine the frequency (n = 4,111) and inter-assay reproducibility (n = 1,752)
      of ER/PR subtypes (ER+/PR+, ER+/PR-, ER-/PR-, ER-/PR+). To extend our findings,
      we utilized a cohort of patients from the Nurses' Health Study (NHS) with ER/PR
      data recorded in the medical record and assessed on tissue microarrays (n =
      2,011). In both datasets, we assessed the association of ER and PR expression
      with survival. RESULTS: In a genome-wide analysis, progesterone receptor was
      among the least variable genes in ER- breast cancer. The ER-/PR+ subtype was rare
      (approximately 1 to 4%) and showed no significant reproducibility (Kappa = 0.02
      and 0.06, in the GEM and NHS datasets, respectively). The vast majority of
      patients classified as ER-/PR+ in the medical record (97% and 94%, in the GEM and
      NHS datasets) were re-classified by a second method. In the GEM dataset (n =
      2,731), progesterone receptor mRNA expression was associated with prognosis in
      ER+ breast cancer (adjusted P <0.001), but not in ER- breast cancer (adjusted P =
      0.21). PR protein expression did not contribute significant prognostic
      information to multivariate models considering ER and other standard clinico
      pathologic features in the GEM or NHS datasets. CONCLUSION: ER-/PR+ breast cancer
      is not a reproducible subtype. PR expression is not associated with prognosis in
      ER- breast cancer, and PR does not contribute significant independent prognostic
      information to multivariate models considering ER and other standard clinico
      pathologic factors. Given that PR provides no clinically actionable information
      in ER+ breast cancer, these findings question the utility of routine PR testing
      in breast cancer.

PMID- 23971949
TI  - Is there a link between mean platelet volume and thrombotic events in
      antiphospholipid syndrome?
AB  - The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the
      production of antiphospholipid antibodies (aPL) that promote vascular thrombosis
      and pregnancy loss. APS can occur in the absence of underlying or associated
      disease (primary APS) or in combination with other diseases (secondary APS). Mean
      platelet volume (MPV) is largely regarded as a useful surrogate marker of
      platelet activation. We aimed to investigate if there is a relationship between
      MPV and thrombotic events in APS. The study consisted of 22 patients and 22
      healthy controls. Group 1 is defined as all the patients in the first day of
      thrombotic event. Group 2 is defined as the same patient population three months
      after the thrombotic event. The erythrocyte sedimentation rate, C-reactive
      protein, white blood cell count, platelet count, and MPV levels were
      retrospectively recorded from patient files. Statistical analyses showed that MPV
      was significantly higher in group 1 than group 2 (p < 0.0001) and healthy
      controls (p < 0.05). However, there was no difference between group 2 and healthy
      controls (p = 0.888). WBC, hemoglobin and other platelet indices such as platelet
      distribution width and platecrit did not differ in groups. In conclusion, MPV was
      increased at initial thrombotic event of APS, and then it was normalized three
      months later by therapeutic interventions. To our knowledge, this is the first
      study demonstrating a correlation between MPV and thrombotic events in APS.

PMID- 23971950
TI  - Combining inhibitor tolerance and D-xylose fermentation in industrial
      Saccharomyces cerevisiae for efficient lignocellulose-based bioethanol
      production.
AB  - BACKGROUND: In addition to efficient pentose utilization, high inhibitor
      tolerance is a key trait required in any organism used for economically viable
      industrial bioethanol production with lignocellulose biomass. Although recent
      work has succeeded in establishing efficient xylose fermentation in robust
      industrial Saccharomyces cerevisiae strains, the resulting strains still lacked
      sufficient inhibitor tolerance for efficient sugar fermentation in lignocellulose
      hydrolysates. The aim of the present work was to combine high xylose fermentation
      activity and high inhibitor tolerance in a single industrial yeast strain.
      RESULTS: We have screened 580 yeast strains for high inhibitor tolerance using
      undetoxified acid-pretreated spruce hydrolysate and identified a triploid
      industrial baker's yeast strain as having the highest inhibitor tolerance. From
      this strain, a mating competent diploid segregant with even higher inhibitor
      tolerance was obtained. It was crossed with the recently developed D-xylose
      fermenting diploid industrial strain GS1.11-26, with the Ethanol Red genetic
      background. Screening of 819 diploid segregants from the tetraploid hybrid
      resulted in two strains, GSF335 and GSF767, combining high inhibitor tolerance
      and efficient xylose fermentation. In a parallel approach, meiotic recombination
      of GS1.11-26 with a haploid segregant of Ethanol Red and screening of 104
      segregants resulted in a similar inhibitor tolerant diploid strain, GSE16. The
      three superior strains exhibited significantly improved tolerance to inhibitors
      in spruce hydrolysate, higher glucose consumption rates, higher aerobic growth
      rates and higher maximal ethanol accumulation capacity in very-high gravity
      fermentation, compared to GS1.11-26. In complex medium, the D-xylose utilization
      rate by the three superior strains ranged from 0.36 to 0.67 g/g DW/h, which was
      lower than that of GS1.11-26 (1.10 g/g DW/h). On the other hand, in batch
      fermentation of undetoxified acid-pretreated spruce hydrolysate, the three
      superior strains showed comparable D-xylose utilization rates as GS1.11-26,
      probably because of their higher inhibitor tolerance. They produced up to 23%
      more ethanol compared to Ethanol Red. CONCLUSIONS: We have successfully
      constructed three superior industrial S. cerevisiae strains that combine
      efficient D-xylose utilization with high inhibitor tolerance. Since the
      background strain Ethanol Red has a proven record of successful industrial
      application, the three new superior strains have strong potential for direct
      application in industrial bioethanol production.

PMID- 23971951
TI  - Partly reversible central auditory dysfunction induced by cerebral vasospasm
      after subarachnoid hemorrhage.
AB  - The authors describe a rare case of central auditory dysfunction induced by
      cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). A 55-year-old
      woman who was admitted after aneurysmal SAH developed cerebral vasospasm on Day 3
      affecting mainly the right middle cerebral artery (MCA) and partly the left MCA.
      The vasospasm became refractory to conventional therapy and was ultimately
      improved by intraarterial infusion of nimodipine in the right MCA and
      angioplasty. Severe auditory dysfunction was apparent from Day 10 as the patient
      was not reactive to speech or environmental sounds. Brain MRI on Day 17
      demonstrated infarcted areas mainly in the right hippocampus, medial occipital
      lobe, and thalamus. The patient underwent further examination using audiometry,
      speech testing, auditory evoked potentials, functional MRI, and cerebral PET. The
      initial diagnosis was extended nonverbal agnosia and total pure word deafness.
      The central auditory dysfunction improved over 6 months, with persisting
      hyperacusis, tinnitus, and amusia. Central auditory dysfunction is a rare
      complication after SAH. While cortical deafness may be associated with bilateral
      lesions of the temporal cortex, partly reversible central auditory dysfunction
      was observed in this patient after prominently unilateral right temporal lesions.
      The role of the interthalamic connections can be discussed, as well as the
      possibility that a less severe vasospasm on the left MCA could have transiently
      impaired the left thalamocortical auditory pathways. 

PMID- 23971952
TI  - Role of subconcussion in repetitive mild traumatic brain injury.
AB  - Research now suggests that head impacts commonly occur during contact sports in
      which visible signs or symptoms of neurological dysfunction may not develop
      despite those impacts having the potential for neurological injury. Recent
      biophysics studies utilizing helmet accelerometers have indicated that athletes
      at the collegiate and high school levels sustain a surprisingly high number of
      head impacts ranging from several hundred to well over 1000 during the course of
      a season. The associated cumulative impact burdens over the course of a career
      are equally important. Clinical studies have also identified athletes with no
      readily observable symptoms but who exhibit functional impairment as measured by
      neuropsychological testing and functional MRI. Such findings have been
      corroborated by diffusion tensor imaging studies demonstrating axonal injury in
      asymptomatic athletes at the end of a season. Recent autopsy data have shown that
      there are subsets of athletes in contact sports who do not have a history of
      known or identified concussions but nonetheless have neurodegenerative pathology
      consistent with chronic traumatic encephalopathy. Finally, emerging laboratory
      data have demonstrated significant axonal injury, blood-brain barrier
      permeability, and evidence of neuroinflammation, all in the absence of behavioral
      changes. Such data suggest that subconcussive level impacts can lead to
      significant neurological alterations, especially if the blows are repetitive. The
      authors propose "subconcussion" as a significant emerging concept requiring
      thorough consideration of the potential role it plays in accruing sufficient
      anatomical and/or physiological damage in athletes and military personnel, such
      that the effects of these injuries are clinically expressed either
      contemporaneously or later in life. 

PMID- 23971953
TI  - Effect of antiplatelet therapy on thromboembolism after flow diversion with the
      pipeline embolization device.
AB  - OBJECT: Flow-diverting stents offer a novel treatment approach to intracranial
      aneurysms. Data regarding the incidence of acute procedure-related thromboembolic
      complications following deployment of the Pipeline Embolization Device (PED)
      remain scant. The authors sought to determine the rate of embolic events in a bid
      to identify potential risk factors and assess the role of platelet inhibition.
      METHODS: Data in all patients receiving a PED for treatment of an intracranial
      aneurysm were prospectively maintained in a database. Diffusion-weighted 3-T MRI
      was performed within 24 hours of PED deployment. The incident rate of procedural
      embolism was established, and univariate analysis was then performed to determine
      any associations of embolic events with measured variables. The degree of
      platelet inhibition in response to aspirin and clopidogrel was evaluated by
      challenging the platelet samples with arachidonic acid and adenosine diphosphate,
      respectively, and then performing formal light transmission platelet
      aggregometry. RESULTS: Twenty-three patients with 26 aneurysms were eligible for
      inclusion in the study. Thirty-one PEDs were deployed in 25 procedures. All
      ischemic lesions detected on diffusion-weighted 3-T MRI were identified as
      embolic based on their location and distribution, with none appearing to be due
      to perforator artery occlusion. Procedural embolic events were found in the
      target parent vessel territory in 13 (52%) of 25 procedures, with no patients
      harboring lesions contralateral to the deployed PED. The number of embolic events
      per procedure ranged from 3 to 16, with a mean of 5.4. There was no significant
      difference between cases with and without procedural embolism in platelet
      inhibition by aspirin (mean 15% vs 12% residual activation; p = 0.28), platelet
      inhibition by clopidogrel (mean 41% vs 41% residual activation; p = 0.98), or
      intraprocedural heparin-induced anticoagulation (mean activated clotting time 235
      seconds vs 237 seconds; p = 0.81). By multivariate analysis, the authors
      identified larger aneurysm size (p = 0.03) as the single variable significantly
      associated with procedural embolism. There was no significant relationship
      between aneurysm size and the number of embolic events (p = 0.32) or the total
      burden of the embolism lesion area (p = 0.53). CONCLUSIONS: Acute embolism
      following use of the PED for treatment of intracranial aneurysms is more common
      than hypothesized. The only identifiable risk factor for embolism appears to be
      greater aneurysm size, perhaps indicating significant disturbed flow across the
      aneurysm neck with ingress and egress through the PED struts. The strength of
      antiplatelet therapy, as measured by residual platelet aggregation, did not
      appear to be associated with cases of procedural embolism. Further work is needed
      to determine the implications of these findings and whether anticoagulation
      regimens can be altered to lower the rate of complications following PED
      deployment.

PMID- 23971954
TI  - Intracranial pressure monitoring in severe head injury: compliance with Brain
      Trauma Foundation guidelines and effect on outcomes: a prospective study.
AB  - OBJECT: The Brain Trauma Foundation (BTF) has established guidelines for
      intracranial pressure (ICP) monitoring in severe traumatic brain injury (TBI).
      This study assessed compliance with these guidelines and the effect on outcomes.
      METHODS: This is a prospective, observational study including patients with
      severe blunt TBI (Glasgow Coma Scale score <= 8, head Abbreviated Injury Scale
      score >= 3) between January 2010 and December 2011. Demographics, clinical
      characteristics, laboratory profile, head CT scans, injury severity indices, and
      interventions were collected. The study population was stratified into 2 study
      groups: ICP monitoring and no ICP monitoring. Primary outcomes included
      compliance with BTF guidelines, overall in-hospital mortality, and mortality due
      to brain herniation. Secondary outcomes were ICU and hospital lengths of stay.
      Multiple regression analyses were deployed to determine the effect of ICP
      monitoring on outcomes. RESULTS: A total of 216 patients met the BTF guideline
      criteria for ICP monitoring. Compliance with BTF guidelines was 46.8% (101
      patients). Patients with subarachnoid hemorrhage and those who underwent
      craniectomy/craniotomy were significantly more likely to undergo ICP monitoring.
      Hypotension, coagulopathy, and increasing age were negatively associated with the
      placement of ICP monitoring devices. The overall in-hospital mortality was
      significantly higher in patients who did not undergo ICP monitoring (53.9% vs
      32.7%, adjusted p = 0.019). Similarly, mortality due to brain herniation was
      significantly higher for the group not undergoing ICP monitoring (21.7% vs 12.9%,
      adjusted p = 0.046). The ICU and hospital lengths of stay were significantly
      longer in patients subjected to ICP monitoring. CONCLUSIONS: Compliance with BTF
      ICP monitoring guidelines in our study sample was 46.8%. Patients managed
      according to the BTF ICP guidelines experienced significantly improved survival.

PMID- 23971955
TI  - Electrostatic discharges and their effect on the validity of registered values in
      intracranial pressure monitors.
AB  - OBJECT: Intracranial pressure (ICP) monitoring is used extensively in clinical
      practice, and as such, the accuracy of registered ICP values is paramount.
      Clinical observations of nonphysiological changes in ICP have called into
      question the accuracy of registered ICP values. Subsequently, the authors have
      tried to determine if the ICP monitors from major manufacturers were affected by
      electrostatic discharges (ESDs), if the changes were permanent or transient in
      nature, and if the changes were modified by the addition of different electrical
      appliances normally used in the neurointensive care unit environment. METHODS:
      The authors established a test setup in the neurointensive care unit using a
      large container filled with isotonic saline, creating a phantom patient.
      Intracranial pressure monitors were sequentially lowered into the container and
      subjected to a predefined test battery of ESDs. RESULTS: Five pressure monitors
      from 4 manufacturers were evaluated. Three monitors containing electrical
      circuitry at the tip of the transducer were all affected by ESDs. Clinically
      significant permanent changes in the reported ICP values for 1 pressure monitor
      were observed, as well as temporary deflections for 2 other monitors. The
      monitors had different levels of sensitivity to discharges at low voltages.
      CONCLUSIONS: These results explain some of the sudden shifts in ICP noted in the
      clinical setting. However, a clear deflection pattern related to the addition of
      electrical appliances was not found. The authors recommend instituting policies
      for reducing the risk of subjecting patients to ESDs in the neurointensive care
      unit setting.

PMID- 23971956
TI  - Intracranial hypotension masquerading as nonconvulsive status epilepticus: report
      of 3 cases.
AB  - Intracranial hypotension (IH) has been a known entity in neurocritical care since
      1938. Even though many cases are spontaneous, the incidence of intracranial
      hypotension in the neurocritical care setting is increasing by virtue of the
      increased number of neurosurgical interventions. Whether spontaneous or secondary
      in etiology, diagnosis of IH usually requires the presence of orthostatic
      symptoms, including headaches and nausea with low opening CSF pressure. However,
      typical clinical features in the appropriate clinical context and imaging, even
      with normal CSF pressure, can indicate IH. In the neurocritical care setting,
      challenges for accurate semiology include altered sensorium and reduced levels of
      responsiveness for which many etiologies may exist, including metabolic
      dysfunction, traumatic brain injury, IH, or nonconvulsive status epilepticus
      (NCSE). The authors describe 3 patients whose clinical picture and
      electroencephalography (EEG) findings initially suggested NCSE but who did not
      respond to treatment with antiepileptic drugs alone. Neuroimaging suggested IH,
      and subsequent treatment of IH successfully improved the patient's clinical
      status. To the authors' knowledge this paper is the first in the literature that
      reports a correlation of IH with electrographic findings similar to NCSE as cause
      and effect. The authors' hypothesis is that thalamocortical dysfunction causes
      EEG findings that appear to be similar to those in NCSE but that these conditions
      do not coexist. The EEG activity is not epileptogenic, and IH results in blocking
      network pathways producing thalamocortical dysfunction. The authors discuss the
      hypothesis and pathophysiology of these epileptiform changes in relation to IH. 

PMID- 23971957
TI  - Treatment guidelines from the Brain Trauma Foundation.

PMID- 23971958
TI  - Tumor volume as a predictor of survival and local control in patients with brain
      metastases treated with Gamma Knife surgery.
AB  - OBJECT: The aim of this study was to examine tumor volume as a prognostic factor
      for patients with brain metastases treated with Gamma Knife surgery (GKS).
      METHODS: Two hundred fifty patients with 1-14 brain metastases who had initially
      undergone GKS alone at a single institution were retrospectively reviewed.
      Patients who received upfront whole brain radiation therapy were excluded.
      Survival times were estimated using the Kaplan-Meier method. Univariate and
      multivariate analyses using Cox proportional hazard regression models were used
      to determine if various prognostic factors could predict overall survival,
      distant brain failure, and local control. RESULTS: Median overall survival was
      7.1 months and the 1-year local control rate was 91.5%. Median time to distant
      brain failure was 8.0 months. On univariate analysis an increasing total tumor
      volume was significantly associated with worse survival (p = 0.031) whereas the
      number of brain metastases, analyzed as a continuous variable, was not (p =
      0.082). After adjusting for age, Karnofsky Performance Scale score, and
      extracranial disease on multivariate analysis, total tumor volume was found to be
      a better predictor of overall survival (p = 0.046) than number of brain
      metastases analyzed as a continuous variable (p = 0.098). A total tumor volume
      cutoff value of >= 2 cm(3) (p = 0.008) was a stronger predictor of overall
      survival than the number of brain metastases (p = 0.098). Larger tumor volume and
      extracranial disease, but not the number of brain metastases, were predictive of
      distant brain failure on multivariate analysis. Local tumor control at 1 year was
      97% for lesions < 2 cm(3) compared with 75% for lesions >= 2 cm(3) (p < 0.001).
      CONCLUSIONS: After adjusting for other factors, a total brain metastasis volume
      was a strong and independent predictor for overall survival, distant brain
      failure, and local control, even when considering the number of metastases.

PMID- 23971959
TI  - Subconcussion in traumatic brain injury.

PMID- 23971960
TI  - Diffuse low-grade gliomas.

PMID- 23971961
TI  - Glioblastoma.

PMID- 23971962
TI  - Risk of very early recurrent cerebrovascular events in symptomatic carotid artery
      stenosis.
AB  - OBJECT: The risk of recurrence of cerebrovascular events within the first 72
      hours of admission in patients hospitalized with symptomatic carotid artery (CA)
      stenoses and the risks and benefits of emergency CA intervention within the first
      hours after the onset of symptoms are not well known. Therefore, the authors
      aimed to assess (1) the ipsilateral recurrence rate within 72 hours of admission,
      in the period from 72 hours to 7 days, and after 7 days in patients presenting
      with nondisabling stroke, transient ischemic attack (TIA), or amaurosis fugax
      (AF), and with an ipsilateral symptomatic CA stenosis of 50% or more, and (2) the
      risk of stroke in CA interventions within 48 hours of admission versus the risk
      in interventions performed after 48 hours. METHODS: Ninety-four patients were
      included in this study. These patients were admitted to hospital within 48 hours
      of a nondisabling stroke, TIA, or AF resulting from a symptomatic CA stenosis of
      50% or more. The patients underwent carotid endarterectomy (85 patients) or CA
      stenting (9 patients). At baseline, the cardiovascular risk factors of the
      patients, the degree of symptomatic CA stenosis, and the type of secondary
      preventive treatment were assessed. The in-hospital recurrence rate of stroke,
      TIA, or AF ipsilateral to the symptomatic CA stenosis was determined for the
      first 72 hours after admission, from 72 hours to 7 days, and after 7 days.
      Procedure-related cerebrovascular events were also recorded. RESULTS: The median
      time from symptom onset to CA intervention was 5 days (interquartile range 3.00
      9.25 days). Twenty-one patients (22.3%) underwent CA intervention within 48 hours
      after being admitted. Overall, 15 recurrent cerebrovascular events were observed
      in 12 patients (12.8%) in the period between admission and CA intervention: 3
      strokes (2 strokes in progress and 1 stroke) (3.2%), 5 TIAs (5.3%), and 1 AF
      (1.1%) occurred within the first 72 hours (total 9.6%) of admission; 1 TIA (1.1%)
      occurred between 72 hours and 7 days, and 5 TIAs (5.3%) occurred after more than
      7 days. The corresponding actuarial cerebrovascular recurrence rates were 11.4%
      (within 72 hours of admission), 2.4% (between 72 hours and 7 days), and 7.9%
      (after 7 days). Among baseline characteristics, no predictive factors for
      cerebrovascular recurrence were identified. Procedure-related cerebrovascular
      events occurred at a rate of 4.3% (3 strokes and 1 TIA), and procedures performed
      within the first 48 hours and procedures performed after 48 hours had a similar
      frequency of these events (4.5% vs. 4.1%, respectively; p = 0.896). CONCLUSIONS:
      The in-hospital recurrence of cerebrovascular events was quite low, but all
      recurrent strokes occurred within 72 hours. The risk of stroke associated with a
      CA intervention performed within the first 48 hours was not increased compared
      with that for later interventions. This raises the question of the optimal timing
      of CA intervention in symptomatic CA stenosis. To answer this question, more data
      are needed, preferably from large randomized trials.

PMID- 23971963
TI  - Magnetic resonance imaging and thermal injury.

PMID- 23971964
TI  - Factors predicting postoperative hyponatremia and efficacy of hyponatremia
      management strategies after more than 1000 pituitary operations.
AB  - OBJECT: Syndrome of inappropriate antidiuretic hormone secretion-induced
      hyponatremia is a common morbidity after pituitary surgery that can be profoundly
      symptomatic and cause costly readmissions. The authors calculated the frequency
      of postoperative hyponatremia after 1045 consecutive operations and determined
      the efficacy of interventions correcting hyponatremia. METHODS: The authors
      performed a retrospective review of 1045 consecutive pituitary surgeries in the
      first 946 patients treated since forming a dedicated pituitary center 5 years
      ago. Patients underwent preoperative and daily inpatient sodium checks, with
      outpatient checks as needed. RESULTS: Thirty-two patients presented with
      hyponatremia; 41% of these patients were symptomatic. Postoperative hyponatremia
      occurred after 165 operations (16%) a mean of 4 days after surgery (range 0-28
      days); 19% of operations leading to postoperative hyponatremia were associated
      with postoperative symptoms (38% involved dizziness and 29% involved
      nausea/vomiting) and 15% involved readmission for a mean of 5 days (range 1-20
      days). In a multivariate analysis including lesion size, age, sex, number of
      prior pituitary surgeries, surgical approach, pathology, lesion location, and
      preoperative hypopituitarism, only preoperative hypopituitarism predicted
      postoperative hyponatremia (p = 0.006). Of patients with preoperative
      hyponatremia, 59% underwent medical correction preoperatively and 56% had
      persistent postoperative hyponatremia. The mean correction rates were 0.4
      mEq/L/hr (no treatment; n = 112), 0.5 mEq/L/hr (free water restriction; n = 24),
      0.7 mEq/L/hr (salt tablets; n = 14), 0.3 mEq/L/hr (3% saline; n = 20), 0.7
      mEq/L/hr (intravenous vasopressin receptor antagonist Vaprisol; n = 22), and 1.2
      mEq/L/hr (oral vasopressin receptor antagonist tolvaptan; n = 9) (p = 0.002,
      ANOVA). While some patients received more than 1 treatment, correction rates were
      only recorded when a treatment was given alone. CONCLUSIONS: After 1045 pituitary
      operations, postoperative hyponatremia was associated exclusively with
      preoperative hypopituitarism and was most efficiently managed with oral
      tolvaptan, with several interventions insignificantly different from no
      treatment. Promptly identifying hyponatremia in high-risk patients and management
      with agents like tolvaptan can improve safety and decrease readmission. For
      readmitted patients with severely symptomatic hyponatremia, the intravenous
      vasopressin receptor antagonist Vaprisol is another treatment option.

PMID- 23971965
TI  - A novel method to assess collagen architecture in skin.
AB  - BACKGROUND: Texture within biological specimens may reveal critical insights,
      while being very difficult to quantify. This is a particular problem in
      histological analysis. For example, cross-polar images of picrosirius stained
      skin reveal exquisite structure, allowing changes in the basketweave conformation
      of healthy collagen to be assessed. Existing techniques measure gross
      pathological changes, such as fibrosis, but are not sufficiently sensitive to
      detect more subtle and progressive pathological changes in the dermis, such as
      those seen in ageing. Moreover, screening methods for cutaneous therapeutics
      require accurate, unsupervised and high-throughput image analysis techniques.
      RESULTS: By analyzing spectra of images post Gabor filtering and Fast Fourier
      Transform, we were able to measure subtle changes in collagen fibre orientation
      intractable to existing techniques. We detected the progressive loss of collagen
      basketweave structure in a series of chronologically aged skin samples, as well
      as in skin derived from a model of type 2 diabetes mellitus. CONCLUSIONS: We
      describe a novel bioimaging approach with implications for the evaluation of
      pathology in a broader range of biological situations.

PMID- 23971966
TI  - Computational model of particle deposition in the nasal cavity under steady and
      dynamic flow.
AB  - A computational model for flow and particle deposition in a three-dimensional
      representation of the human nasal cavity is developed. Simulations of steady
      state and dynamic airflow during inhalation are performed at flow rates of 9-60
      l/min. Depositions for particles of size 0.5-20 MUm are determined and compared
      with experimental and simulation results from the literature in terms of
      deposition efficiencies. The nasal model is validated by comparison with
      experimental and simulation results from the literature for particle deposition
      under steady-state flow. The distribution of deposited particles in the nasal
      cavity is presented in terms of an axial deposition distribution as well as a
      bivariate axial deposition and particle size distribution. Simulations of dynamic
      airflow and particle deposition during an inhalation cycle are performed for
      different nasal cavity outlet pressure variations and different particle
      injections. The total particle deposition efficiency under dynamic flow is found
      to depend strongly on the dynamics of airflow as well as the type of particle
      injection. 

PMID- 23971967
TI  - Observation of nanoscale cooling effects by substrates and the surrounding media
      for single gold nanoparticles under CW-laser illumination.
AB  - Understanding the nanoscale heating-induced local thermal response is important
      but hampered by lack of information on temperatures at such small scales. This
      paper reports laser-induced heating and thermal equilibration of metal
      nanoparticles supported on different substrates and immersed in several media. We
      use single-particle spectroscopy to monitor nanoparticle temperature rises due to
      laser excitation. Because of changes in the refractive index of the surrounding
      medium, the scattering spectrum of the gold nanoparticles undergoes a shift that
      is related to the temperature of the system. We find that the temperature
      increase depends on both the surrounding medium and the supporting substrate. We
      furthermore model the nanoparticle temperature using a simplified 1-D heat
      conduction model with an effective thermal conductivity that takes both substrate
      and environment into account. The results from this model are also compared to a
      more detailed 2-D heat transfer analysis. The results presented here are quite
      new and important to many plasmonic nanoparticle applications where the strong
      absorption cross section of the nanoparticles leads to a significant temperature
      rise. In particular, the current work introduces an analysis that can be easily
      implemented to model the temperature of a nanoparticle supported on a substrate,
      as is the case in many single-particle measurements. 

PMID- 23971968
TI  - Striatal denervation pattern predicts levodopa effects on sequence learning in
      Parkinson's disease.
AB  - Mild to moderate Parkinson's disease shows more denervation in the posterodorsal
      striatum and sparing of the anteroventral striatum. Dopaminergic medications can
      interfere with anteroventral striatum function by overdosing this relatively
      intact structure. The authors determined how regional striatal denervation
      affects medication-associated sequence learning impairment in Parkinson's
      disease. Eighteen Parkinson's patients performed motor sequence learning on and
      off levodopa. Patients underwent (11)C-dihydrotetrabenazine positron emission
      tomography scans to measure nigrostriatal denervation. Patients with more
      preserved putamen were more likely to exhibit levodopa-associated sequence
      learning impairments. Furthermore, the ratio of denervation in the anterior to
      posterior dorsal putamen predicted the level of learning differences on and off
      levodopa. These results demonstrate that the spatial pattern of nigrostriatal
      dopaminergic denervation predicts medication responsiveness for motor sequence
      learning.

PMID- 23971969
TI  - Phase transition between layered tungstates and polyoxotungstates in aqueous
      solutions.
AB  - Aqueous sols of colloidal layered tetramethylammonium (TMA) tungstate
      nanocrystals were obtained by diluting an aqueous suspension of TMA
      polyoxotungstate precipitates. The slow evaporation of the colloidal-layered
      tungstate sols led to the deposition of TMA polyoxotungstate and significantly
      decreased the amount of layered tungstate nanocrystals. Moreover, the increase in
      the amount of TMA(+) in the sols also facilitated precipitation of the
      polyoxotungstates because of a common ion effect. Thus, the dissolution and
      formation of polyoxotungstate were reversible phenomena. The reaction between the
      dissolved species, which were formed by the dissolution of TMA polyoxotungstate,
      likely provided the highly water-dispersible layered tungstate nanocrystals.
      Furthermore, transmission electron microscopy observation suggested that the
      layered tungstate nanocrystals had a layer structure similar to those of H2WO4
      and H2WO4.H2O, which is a layered tungstic acid. 

PMID- 23971970
TI  - Oral BG-12 (dimethyl fumarate) for relapsing-remitting multiple sclerosis: a
      review of DEFINE and CONFIRM. Evaluation of: Gold R, Kappos L, Arnold D, et al.
      Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis.
      N Engl J Med 2012;367:1098-107; and Fox RJ, Miller DH, Phillips JT, et al.
      Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple
      sclerosis. N Engl J Med 2012;367:1087-97.
AB  - INTRODUCTION: Multiple sclerosis (MS) is an autoimmune neurodegenerative disease
      of the central nervous system involving inflammation, chronic demyelination and
      axonal loss. MS affects more than 2 million people worldwide. AREAS COVERED: This
      article aims to summarize the findings from two pivotal 2-year, randomized,
      double-blind, placebo-controlled, Phase III studies of BG-12 (dimethyl fumarate)
      for relapsing-remitting MS (RRMS): DEFINE (Determination of the Efficacy and
      Safety of Oral Fumarate in RRMS) and CONFIRM (Comparator and an Oral Fumarate in
      RRMS). Results from both studies demonstrated that BG-12 provides clinical and
      radiological efficacy over 2 years across a range of outcomes. These results were
      apparent as early as 12 weeks and sustained over the course of both studies. BG
      12 was found to have an acceptable safety profile, with a similar overall
      incidence of adverse events across all treatment groups. EXPERT OPINION: The
      combination of robust efficacy, ease of administration and established safety
      profile is unique to a new therapy in MS. Findings from the pivotal Phase III
      studies support BG-12 as a potential initial oral treatment for patients with
      RRMS or as an alternative to other currently available therapies.

PMID- 23971971
TI  - Association between the hOGG1 Ser326Cys polymorphism and lung cancer
      susceptibility: a meta-analysis based on 22,475 subjects.
AB  - OBJECTIVES: The Ser326Cys polymorphism in the human 8-oxogunaine glycosylase
      (hOGG1) gene with lung cancer susceptibility had been investigated, but results
      were inconsistent and underpowered. The aim of this study was to conduct a meta
      analysis assessing the association of hOGG1 Ser326Cys polymorphism with risk of
      lung cancer. MATERIALS AND METHODS: Relevant studies were identified through a
      search of MEDLINE, PubMed, Web of Science, EMBASE, and Chinese Biomedical
      Literature database (CBM) using terms "lung cancer", "hOGG1" or "OGG1",
      "polymorphism" or "variation" and the last search updated on May 1, 2013. In this
      meta-analysis, we assessed 30 published studies involving 22,475 subjects that
      investigated the association between the hOGG1 Ser326Cys polymorphism and lung
      cancer susceptibility. RESULTS: Overall, the hOGG1 Ser326Cys polymorphism was not
      associated with lung cancer susceptibility in different genetic models (dominant
      model comparison: OR = 0.133; 95% CI = 0.111-0.161; P(heterogeneity) = 0.000),
      and recessive model: OR = 0.543; 95% CI = 0.399-0.739; P(heterogeneity) = 0.000).
      Similarly, in the stratified analyses by ethnicity, significantly increased risks
      were found among Asians for homozygote comparison (OR = 0.850; 95% CI = 0.732
      0.986; P(heterogeneity) = 0.064), and dominant model (OR = 0.160; 95% CI = 0.137
      0.187; P(heterogeneity) = 0.001), and Caucasians for dominant model (OR = 1.35;
      95% CI = 1.03-1.77; P(heterogeneity) = 0.015), and recessive model (OR = 1.35;
      95% CI = 1.03-1.77; P(heterogeneity) = 0.015). In population-based populations,
      marginally significant increased risks were found in dominant model (OR = 0.143;
      95% CI = 0.111 0.184; P(heterogeneity) = 0.000) and recessive model (OR = 0.429;
      95% CI = 0.261-0.705; P(heterogeneity) = 0.000). We also found a significant
      difference between hOGG1 Ser326Cys genotype and lung cancer susceptibility in
      studies with hospital-based controls for homozygote model (OR = 0.798; 95% CI =
      0.649-0.982; P(heterogeneity )= 0.007),dominant model (OR = 0.122; 95% CI = 0.091
      0.163; P(heterogeneity) = 0.000). CONCLUSION: Our data showed that the hOGG1
      Ser326Cys polymorphism contributed to the risk of lung cancer. VIRTUAL SLIDES:
      The virtual slides for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/3842531131031605.

PMID- 23971973
TI  - Excited state structures and decay dynamics of 1,3-dimethyluracils in solutions:
      resonance Raman and quantum mechanical calculation study.
AB  - The resonance Raman spectroscopic study of the excited state structural dynamics
      of 1,3-dimethyluracil (DMU), 5-bromo-1,3-dimethyluracil (5BrDMU), uracil, and
      thymine in water and acetonitrile were reported. Density functional theory
      calculations were carried out to help elucidate the ultraviolet electronic
      transitions associated with the A-, and B-band absorptions and the vibrational
      assignments of the resonance Raman spectra. The effect of the methylation at N1,
      N3 and C5 sites of pyrimidine ring on the structural dynamics of uracils in
      different solvents were explored on the basis of the resonance Raman intensity
      patterns. The relative resonance Raman intensities of DMU and 5BrDMU are computed
      at the B3LYP-TD level. Huge discrepancies between the experimental resonance
      Raman intensities and the B3LYP-TD predicted ones were observed. The underlying
      mechanism was briefly discussed. The decay channel through the
      S1((1)npi*)/S2((1)pipi*) conical intersection and the S1((1)npi*)/T1((3)pipi*)
      intersystem crossing were revealed by using the CASSCF(8,7)/6-31G(d) level of
      theory calculations. 

PMID- 23971972
TI  - The majority of HIV type 1 DNA in circulating CD4+ T lymphocytes is present in
      non-gut-homing resting memory CD4+ T cells.
AB  - Memory CD4(+) T lymphocytes in peripheral blood that express integrins
      alpha4beta7 preferentially recirculate through gut-associated lymphoid tissue
      (GALT), a proposed site of significant HIV-1 replication. Tregs and activated
      CD4(+) T cells in GALT could also be particularly susceptible to infection. We
      therefore hypothesized that infection of these subsets of memory CD4(+) T cells
      may contribute disproportionately to the HIV-1 reservoir. A cross-sectional study
      of CD4(+) T cell subsets of memory CD45RO(+) cells in peripheral blood
      mononuclear cells (PBMCs) was conducted using leukapheresis from eight subjects
      with untreated chronic HIV-1 infection. Real-time polymerase chain reaction (PCR)
      was used to quantify total and integrated HIV-1 DNA levels from memory CD4(+) T
      cells sorted into integrin beta7(+) vs. beta7(-), CD25(+)CD127(low) Treg vs.
      CD127(high), and activated CD38(+) vs. CD38(-). More than 80% of total HIV-1 DNA
      was found to reside in the integrin beta7-negative non-gut-homing subset of
      CD45RO(+) memory CD4(+) T cells. Less than 10% was found in highly purified Tregs
      or CD38(+) activated memory cells. Similarly, integrated HIV-1 DNA copies were
      found to be more abundant in resting non-gut-homing memory CD4(+) T cells (76%)
      than in their activated counterparts (23%). Our investigations showed that the
      majority of both total and integrated HIV-1 DNA was found within non-gut-homing
      resting CD4(+) T cells.

PMID- 23971974
TI  - HIV/AIDS-related attitudes and oral impacts on daily performances: a cross
      sectional study of Sudanese adult dental patients.
AB  - BACKGROUND: Few studies have investigated the relationships between HIV-related
      knowledge, fear of contagion in dental environments and Oral Impacts on Daily
      Performance (OIDP) among dental patients. Our objectives were to investigate the
      associations between HIV-related knowledge and fear of contagion in dental
      environments and OIDP among dental patients, and to evaluate whether those
      associations were modified by the frequency of dental service attendance.
      METHODS: A total of 1262 patients (mean age 30.7 years, 56.5% females) were
      recruited from the Khartoum Dental Teaching Hospital and the University of
      Science and Technology during March-July 2008. The participants underwent a full
      mouth oral clinical examination and completed an interview in a face-to-face
      setting. RESULTS: Of the study participants, 41.4% had visited a dentist at least
      twice during the last 2 years, 96.2% had caries experience (DT > 0) and 79.1%
      reported oral impacts (OIDP > 0). The most frequently reported oral impacts were
      problems eating, sleeping and cleaning teeth. In total, 26.3% of the participants
      had HIV transmission knowledge, 75.6% knew people with HIV/AIDS and 58.7%
      perceived a high risk of cross-infection in dental environments. After adjusting
      for sociodemographic characteristics, frequency of dental service attendance and
      caries experience, patients who had high HIV-related information exposure, a
      positive attitude toward people with HIV/AIDS and a high perceived risk of cross
      infection were more likely to report oral impacts, whereas patients who knew
      people with HIV/AIDS were less likely to report oral impacts. The association
      between OIDP and HIV transmission knowledge was modified by frequency of dental
      service attendance. CONCLUSIONS: Dental patients who were informed about HIV and
      had a high HIV/AIDS risk perception were more likely to report impaired oral
      health-related quality of life than their less informed counterparts and those
      who perceived a low risk of contagion. The effect of HIV transmission knowledge
      on oral impacts was influenced by frequency of dental service attendance.

PMID- 23971975
TI  - VEGF A (rs699947 and rs833061) and VEGFR2 (rs2071559) gene polymorphisms are not
      associated with AMD susceptibility in a Spanish population.
AB  - PURPOSE: Age-related macular degeneration (AMD) is a multifactorial disease due
      to interaction between genetic and environmental factors. Increased angiogenesis
      plays a central role in AMD development. Previous studies on the potential link
      between AMD and vascular endothelial growth factor (VEGFA) and vascular
      endothelial growth factor receptor (VEGFR) have yielded conflicting results. We
      have analysed if polymorphisms in genes coding for VEGFA and VEGFR are associated
      to susceptibility to suffer AMD in a cohort of Spanish subjects. PATIENTS AND
      METHODS: We obtained peripheral blood samples from 151 patients with diagnosis of
      exudative AMD. We also studied 91 healthy subjects matched by age. We studied
      VEGFA rs699947 and rs833061, and VEGFR2 rs2071559 polymorphisms using real-time
      PCR with TaqMan probes. RESULTS: We did not find statistically significant
      differences in genotypic distribution of VEGF rs699947 and rs833061 polymorphisms
      between patients and controls. However, analysis of VEGFR2 rs2071559 polymorphism
      shows that carriers of GG genotype are more frequent in subjects with AMD (p:
      0.032; Odds Ratio(OR): 1.933; confidence interval (CI): 1.053-3.549), but, when
      corrected by Bonferroni testing, the result was found to be not significant.
      CONCLUSION: Our study shows that VEGFA rs699947 and rs833061 and VEGFR2 rs2071559
      polymorphisms do not modify the risk of suffering AMD in a Spanish population.

PMID- 23971976
TI  - Effect of zinc ions on improving implant fixation in osteoporotic bone.
AB  - The application of titanium (Ti) and its alloys in tooth restoration and joint
      replacement for aged patients with unfavorable conditions is gaining popularity.
      Therefore, strategies aiming at improving the fixation of Ti-based implants are
      worth investigating. This study was designed to observe whether modification of
      Ti implants by zinc (Zn) could enhance the fixation capability in osteoporotic
      bone. Two kinds of implants, hydroxyapatite (HA) coated Ti and Zn-incorporated HA
      (ZnHA) coated Ti, were inserted into the femoral metaphysis longitudinally in
      ovariectomized (OVX) rats. Specimens were harvested and subjected to double
      fluorescence labeling examination at week 6 after surgery. At week 12, samples
      were evaluated with histomorphometry, micro-CT (MUCT) analysis and biomechanical
      test. Compared to the HA coated implants, ZnHA coating improved mineral
      apposition rate (MAR) of peri-implant bone, which was revealed by double
      fluorescence labeling; bone area ratio (BA) and bone-to-implant contact (BIC)
      were also higher for the latter group by histomorphometry. MUCT images suggested
      that more bone mass was formed around the ZnHA coated implants as compared to the
      HA coated implants. Biomechanical push-out test showed that the ZnHA coated
      implants demonstrated higher strength of osseointegration than the HA group. The
      current study suggested that Zn ions could enhance bone formation and improve
      implant fixation in OVX rats.

PMID- 23971977
TI  - Conditional probabilistic analysis for prediction of the activity landscape and
      relative compound activities.
AB  - Structure-property relationships and structure-activity relationships play an
      important role in many research areas, such as medicinal chemistry and drug
      discovery. Such methods, however, have focused on providing post-hoc descriptions
      of such relationships based on known data. The ability for these descriptions to
      remain relevant when considering compounds of unknown activity, and thus the
      prediction of activity and property landscapes using existing data, remains
      little explored. In this study, we present a novel method of evaluating the
      ability of a compound comparison methodology to provide accurate information
      about a set of unknown compounds and also explore the ability of these predicted
      activity landscapes to prioritize active compounds over inactive. These methods
      are applied to three distinct and diverse sets of compounds, each with activity
      data for multiple targets, for a total of eight target-compound set pairs. Six
      methodologically distinct compound comparison methods were evaluated. We show
      that overall, all compound comparison methods provided an improvement in
      structure-activity relationship prediction over random and were able to
      prioritize compounds in a superior manner to random sampling, but the degree of
      success and therefore applicability varied markedly. 

PMID- 23971980
TI  - Facile rearrangement of 3-oxoalkyl radicals is evident in low-temperature gas
      phase oxidation of ketones.
AB  - The pulsed photolytic chlorine-initiated oxidation of methyl-tert-butyl ketone
      (MTbuK), di-tert-butyl ketone (DTbuK), and a series of partially deuterated
      diethyl ketones (DEK) is studied in the gas phase at 8 Torr and 550-650 K.
      Products are monitored as a function of reaction time, mass, and photoionization
      energy using multiplexed photoionization mass spectrometry with tunable
      synchrotron ionizing radiation. The results establish that the primary 3-oxoalkyl
      radicals of those ketones, formed by abstraction of a hydrogen atom from the
      carbon atom in gamma-position relative to the carbonyl oxygen, undergo a rapid
      rearrangement resulting in an effective 1,2-acyl group migration, similar to that
      in a Dowd-Beckwith ring expansion. Without this rearrangement, peroxy radicals
      derived from MTbuK and DTbuK cannot undergo HO2 elimination to yield a closed
      shell unsaturated hydrocarbon coproduct. However, not only are these coproducts
      observed, but they represent the dominant oxidation channels of these ketones
      under the conditions of this study. For MTbuK and DTbuK, the rearrangement yields
      a more stable tertiary radical, which provides the thermodynamic driving force
      for this reaction. Even in the absence of such a driving force in the oxidation
      of partially deuterated DEK, the 1,2-acyl group migration is observed. Quantum
      chemical (CBS-QB3) calculations show the barrier for gas-phase rearrangement to
      be on the order of 10 kcal mol(-1). The MTbuK oxidation experiments also show
      several minor channels, including beta-scission of the initial radicals and
      cyclic ether formation. 

PMID- 23971981
TI  - The origins of neocortex: connections and lamination as distinct events in
      evolution.
AB  - In the nonmammalian telencephalon, there are neuronal populations corresponding
      to cell groups in the neocortex of mammals in terms of connections, single unit
      responses, chemical content, and functions. Some of these populations in
      nonmammals, however, are organized in a nonlaminar, rather than laminar fashion.
      These observations may prompt a reassessment of the functional roles of
      lamination and the evolutionary origins of the mammalian neocortex. Thus, the
      role of neural circuits and laminar organization can be differentiated in order
      to understand the cognitive functions of the neocortex. Moreover, the origins of
      neocortex can be separable into the precursors of nonlaminar and laminar regions.

PMID- 23971979
TI  - PIK3CA mutations are frequently observed in BRCAX but not BRCA2-associated male
      breast cancer.
AB  - INTRODUCTION: Although a substantial proportion of male breast cancers (MBCs) are
      hereditary, the molecular pathways that are activated are unknown. We therefore
      examined the frequency and clinicopathological associations of the
      PIK3CA/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase
      (MAPK) pathways and their regulatory genes in familial MBC. METHODS: High
      resolution melting analysis and confirmatory sequencing was used to determine the
      presence of somatic mutations in PIK3CA (exon 9 and 20), AKT1 (exon 4), KRAS
      (exon 2) and BRAF (exon 15) genes in 57 familial MBCs. Further analysis of the
      PIK3CA/mTOR pathway was performed using immunohistochemistry for the pAKT1, pS6
      and p4EBP1 biomarkers. RESULTS: PIK3CA somatic mutations were identified in 10.5%
      (6 of 57) of cases; there were no AKT1, KRAS or BRAF somatic mutations. PIK3CA
      mutations were significantly more frequent in cancers from BRCAX patients (17.2%,
      5/29) than BRCA2 (0%, 0/25) carriers (P = 0.030). Two BRCAX patients had an E547K
      mutation which has only been reported in one female breast cancer previously.
      PIK3CA mutation was significantly correlated with positive pS6 (83.3% vs. 32.0%,
      P = 0.024) and negative p4EBP1 (100% vs. 38.0%, P = 0.006) expression, but not
      pAKT expression. Expression of nuclear p4EBP1 correlated with BRCA2 mutation
      carrier status (68.0% vs. 38.7%, P = 0.035). CONCLUSIONS: Somatic PIK3CA mutation
      is present in familial male breast cancer but absent in BRCA2 carriers. The
      presence of two of the extremely rare E547K PIK3CA mutations in our cohort may
      have specific relevance in MBCs. Further study of PIK3CA in MBCs, and in
      particular BRCAX patients, may contribute to further establishing the relevance
      of specific PIK3CA mutations in MBC aetiology and in the identification of
      particular patient groups most likely to benefit from therapeutic targeting with
      the novel PIK3CA inhibitors that are currently in development.

PMID- 23971982
TI  - Brain Activity Underlying Mental Imagery: Event-related Potentials During Mental
      Image Generation.
AB  - This article addresses two issues about the neural bases of mental imagery. The
      first issue concerns the modality-specificity of mental images, that is, whether
      or not they involve activity in visual areas of the brain. The second issue
      concerns hemispheric specialization for the generation of mental images. We
      compared event-related potentials recorded under two conditions: one in which
      subjects were shown words and asked to read them and one in which subjects were
      shown words and asked to read them and generate visual mental images of the
      words' referents. Imagery caused a slow, late positivity, maximal at the
      occipital and posterior temporal regions of the scalp, relative to the comparison
      condition, and consistent with the involvement of modality-specific visual cortex
      in mental imagery. Also noted was an asymmetry in the imagery-related ERP,
      consistent with left-hemisphere specialization for mental image generation.
      Similar results were obtained when subjects listened to auditorily presented
      words with and without instructions to generate mental images. To assess the
      specificity of the relation between these ERP effects and mental imagery, we
      compared the ERP changes brought about by imaging with those brought about by
      another effortful task using the same stimulus words: proofreading the words for
      occasional misspellings. This produced changes that differed in polarity, time
      course, and scalp distribution from the imagery-related changes. 

PMID- 23971978
TI  - Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other
      neuropsychiatric diseases: a novel target in psychopharmacology.
AB  - BACKGROUND: Melatonin (MLT) is a pleiotropic neurohormone controlling many
      physiological processes and whose dysfunction may contribute to several different
      diseases, such as neurodegenerative diseases, circadian and mood disorders,
      insomnia, type 2 diabetes and pain. Melatonin is synthesized by the pineal gland
      during the night and acts through 2 G-protein coupled receptors (GPCRs), MT1
      (MEL1a) and MT2 (MEL1b). Although a bulk of research has examined the
      physiopathological effects of MLT, few studies have investigated the selective
      role played by MT1 and MT2 receptors. Here we have reviewed current knowledge
      about the implications of MT2 receptors in brain functions. METHODS: We searched
      PubMed, Web of Science, Scopus, Google Scholar and articles' reference lists for
      studies on MT2 receptor ligands in sleep, anxiety, neuropsychiatric diseases and
      psychopharmacology, including genetic studies on the MTNR1B gene, which encodes
      the melatonin MT2 receptor. RESULTS: These studies demonstrate that MT2 receptors
      are involved in the pathophysiology and pharmacology of sleep disorders, anxiety,
      depression, Alzheimer disease and pain and that selective MT2 receptor agonists
      show hypnotic and anxiolytic properties. LIMITATIONS: Studies examining the role
      of MT2 receptors in psychopharmacology are still limited. CONCLUSION: The
      development of novel selective MT2 receptor ligands, together with further
      preclinical in vivo studies, may clarify the role of this receptor in brain
      function and psychopharmacology. The superfamily of GPCRs has proven to be among
      the most successful drug targets and, consequently, MT2 receptors have great
      potential for pioneer drug discovery in the treatment of mental diseases for
      which limited therapeutic targets are currently available.

PMID- 23971983
TI  - Microstimulation of a neural-network model for visually guided saccades.
AB  - Microstimulation of many saccadic centers in the brain produces eye movements
      that are not consistent with either a strictly retinal or strictly head-centered
      coordinate coding of eye movements. Rather, stimulation produces some features of
      both types of coordinate coding. Recently we demonstrated a neural network model
      that was trained to localize the position of visual stimuli in head-centered
      coordinates at the output using inputs of eye and retinal position similar to
      those converging on area 7a of the posterior parietal cortex of monkeys (Zipser &
      Andersen 1988; Andersen & Zipser 1988). Here we show that microstimulation of
      this trained network, achieved by fully activating single units in the middle
      layer, produces "saccades" that are very much like the saccades produced by
      stimulating the brain. The activity of the middle-layer units can be considered
      to code the desired location of the eyes in head-centered coordinates; however,
      stimulation of these units does not produce the saccades predicted by a classical
      head-centered coordinate coding because the location in space appears to be coded
      in a distributed fashion among a population of units rather than explicitly at
      the level of single cells. 

PMID- 23971984
TI  - Does scopolamine directly impair memory?
AB  - Enhanced cued recall, a procedure which circumvents inattention and induces
      semantic processing, was used to determine if scopolamine produces direct
      impairment of specific memory mechanisms or indirect impairment of memory
      secondary to impairment of other cognitive processes. In two studies, cognitively
      normal young adults given moderate or high doses of scopolamine maintained
      maximum cued recall in spite of a dose-dependent decrement in free recall. This
      finding suggests that cholinergic blockade may impair memory indirectly through
      effects on other cognitive processes. 

PMID- 23971985
TI  - A source analysis of the late human auditory evoked potentials.
AB  - The intracerebral generators of the human auditory evoked potentials were
      estimated using dipole source analysis of 14-channel scalp recordings. The
      response to a 400-msec toneburst presented every 0.9 sec could be explained by
      three major dipole sources in each temporal lobe. The first was a vertically
      oriented dipole located on the supratemporal plane in or near the auditory
      koniocortex. This contributed to the scalp-recorded N1 wave at 100 msec. The
      second was a vertically oriented dipole source located on the supratemporal plane
      somewhat anterior to the first. This contributed to both the Nl and the sustained
      potential (SP). The third was a laterally oriented dipole source that perhaps
      originated in the magnopyramidal temporal field. This contributed a negative wave
      to the lateral scalp recordings at the latency of 145 msec. A change in the
      frequency of the toneburst elicited an additional negativity in the scalp
      recording -the mismatch negativity (MMN). When the frequency change was large,
      the mismatch negativity was composed of two distinct sources with sequential but
      partially overlapping activities. The earlier corresponded to the Nl dipole
      sources and the later to a more anteriorly located dipole with an orientation
      more lateral than Nl. Only the later source was active when the frequency change
      was small. MMN source activities peaked about 15 msec earlier in the
      contralateral hemisphere, while this difference was only 4 msec for the sources
      of the Nl. 

PMID- 23971986
TI  - The temporal dynamics of event memory: a stage analysis of mnemonic processing by
      man and macaque.
AB  - Extensive anatomical and psychophysical data suggest that macaques can serve as
      surrogates for man in studies of the neural substrates of visual mnemonic
      processing. However, the extent to which mnemonic-mechanisms in macaques can be
      validly compared to those in man depends critically on the demonstration that the
      cognitive strategy and temporal dynamics of mnemonic retrieval are congruent For
      the two species. Seven human and six macaque subjects were tested on identical
      versions of an item recognition task that required the classification of probe
      stimuli as positive or negative according to whether or not they were members of
      a previously defined set of target stimuli. For the human subjects, reaction time
      increased by an average of 24 msec/target. The macaques were able to respond as
      accurately as the human subjects, but each additional target resulted in a
      reaction time increment of only 7 msec. A detailed analysis of the statistical
      properties of the reaction-time distributions indicated that these data do not
      reflect a between-species difference in the efficiency of execution of otherwise
      comparable, serial-exhaustive, retrieval mechanisms. Rather, the data suggest
      that human subjects engage two memory-load dependent processes before generating
      a response, while macaques execute only one of these. Additional data indicate
      that a reaction-time approach toward the analysis of the stages of mnemonic
      processing can provide new insights into the specific nature of mnemonic deficits
      induced by brain damage. 

PMID- 23971987
TI  - Visual search performance in the neglect syndrome.
AB  - Patients with hemispatial neglect fail to respond to stimuli on one side of
      space. We assessed to what extent the complexity and number of visual stimuli on
      both sides determine the severity of neglect. Patients with neglect were required
      to find specified targets in a cluttered visual field. Two sets of stimuli were
      used. One set produced effortless and parallel search performance in normal
      controls; the other set was more complex and produced serial search performance
      in normal controls. Both sets of stimuli resulted in a serial performance pattern
      in the patients. Their baseline search performance on both sides was similar when
      all stimulus items were restricted to one side. A pronounced difference between
      the two sides was evident when stimuli appeared on both sides. Search for targets
      on the intact side of space was unaffected by distractors on the neglected side,
      whereas search for targets on the neglected side was slowed disproportionately by
      distractors on the intact side. The slowing on the neglected side was more severe
      during the more demanding search task and when more items were present on the
      intact side. The results indicate that neglect is associated with an inability to
      move attention from objects on the intact side to items on the neglected side. 

PMID- 23971988
TI  - Erratum.

PMID- 23971990
TI  - Cathepsin B degradable star-shaped peptidic macromolecules for delivery of 2
      methoxyestradiol.
AB  - 2-Methoxyestradiol (2ME), a natural metabolite of estradiol, has
      antiproliferative and antiangiogenic activity. However, its clinical success is
      limited due to poor water solubility and poor pharmacokinetic parameters
      suggesting the need for a delivery vehicle. In this study we evaluated cathepsin
      B degradable star-shaped peptidic macromolecules (SPMs) that can potentially be
      used to create higher generation and high molecular weight peptidic polymer as
      delivery vehicle of 2ME. Two peptidic macromolecules having positively charged
      amine (ASPM) or negatively charged carboxyl surface groups (CSPM) were
      synthesized and evaluated for their degradation in the presence of cathepsin B
      and stability in the presence of neutral or acidic buffer and serum. Both ASPM
      and CSPM degraded rapidly in the presence of cathepsin B. Both were stable in
      neutral and acidic buffer whereas only CSPM exhibited substantial stability in
      the presence of serum. Both macromolecules were nontoxic toward breast cancer
      cells whereas 2ME-containing macromolecules exhibited antiproliferative activity
      in the micromolar range. Overall, results from the current study indicate that
      tetrapeptide GFLG can be used to create star-shaped macromolecules that are
      degraded in the presence of cathepsin B and have the potential to be developed as
      delivery vehicles of 2ME. 

PMID- 23971989
TI  - PlaCor PRT measurement of shear-activated platelet aggregate formation in stable
      patients treated with single and dual antiplatelet therapy.
AB  - Shear forces play a key role in thrombus formation and shear-based tests may
      better reflect physiological conditions in vivo compared with agonist-based
      tests. We evaluated the PlaCor PRT(r), a novel platelet reactivity test based on
      shear-induced platelet aggregation, in patients with stable coronary artery
      disease (CAD) treated with single (SAPT) and dual antiplatelet therapy (DAPT). We
      examined 100 patients with multiple risk factors for CAD and/or documented stable
      CAD: 38 treated with SAPT, aspirin 100 mg qd, 62 treated with DAPT, aspirin 100
      mg + clopidogrel 75 mg qd, compared with age- and sex-matched healthy volunteers
      without antiplatelet therapy (HV, n = 35). Measures of shear-induced platelet
      aggregation were performed with the PlaCor PRT(r). In 25 patients in SAPT, the
      PlaCor test was also performed before and after a 12-hour-loading dose of
      clopidogrel 600 mg. The mean +/- SD PRT time (seconds) in HV was 78 +/- 13 and
      was significantly lower compared with SAPT (118 +/- 16, p = 0.030) and to DAPT
      patients (242 +/- 11, p < 0.0001). A statistically significant difference was
      also reported between SAPT and DAPT patients (p < 0.0001). After a loading dose
      of clopidogrel, the PRT time of SAPT patients increased significantly from 112 +/
      20 to 254 +/- 17, p < 0.0001. 2.7 and 26% of patients were considered as "poor
      responders" to single and dual antiplatelet therapy, respectively. This study
      shows that in patients with multiple risk factors for CAD and/or documented
      stable CAD, SAPT and DAPT play an important role in reducing platelet aggregation
      mediated by shear forces as evaluated with the novel PlaCor PRT(r). Further
      studies will be required to confirm and assess the extent of these findings in
      patients with acute coronary syndromes.

PMID- 23971991
TI  - Distinct visual cues mediate aperture shaping for grasping and pantomime-grasping
      tasks.
AB  - The authors examined whether the top-down requirements of dissociating the
      spatial relations between stimulus and response in a goal-directed grasping task
      renders the mediation of aperture trajectories via relative visual information.
      To address that issue, participants grasped differently sized target objects
      (i.e., grasping condition) and also grasped to a location that was dissociated
      from the target object (i.e., pantomime-grasping condition). Just noticeable
      difference (JND) values associated with the early through late stages of aperture
      shaping were computed to examine the extent to which motor output adhered to, or
      violated, the psychophysical principles of Weber's law. As expected, JNDs during
      the late stages of the grasping condition violated Weber's law: a result evincing
      the use of absolute visual information. In contrast, JNDs for the pantomime
      grasping condition produced a continuous adherence to Weber's law. Such a result
      indicates that dissociating a stimulus from a response is a perception-based task
      and results in aperture shaping via relative visual information.

PMID- 23971993
TI  - Improved efficiency of butanol production by absorbent fermentation with a
      renewable carrier.
AB  - BACKGROUND: Biobutanol production is still not economically competitive because
      of some principal drawbacks including high cost in feedstock consumption, low
      butanol concentration in the fermentation broth caused by severe product
      inhibition. An alternative fermentation mode is becoming an urgent requirement to
      solve these problems. Biobutanol production by absorbent fermentation with a
      renewable carrier, i.e. pretreated straw materials, is studied in this paper.
      RESULTS: Compared with other types of porous media, alkali-treated steam-exploded
      straw was proved to be a suitable carrier for absorbent fermentation of butanol.
      The Acetone-Butanol-Ethanol (ABE) concentration increased by 52% compared with
      submerged culture at an initial glucose concentration of 65 g/L. The adsorption
      of ABE solvent on substrate and increased bacterial concentration alleviated the
      end product inhibition and partly explained this positive effect. The steam
      pretreatment conditions, solid-liquid ratio, substrate types and substrate
      concentration were also investigated. Steam-explosion at 1.1 MPa for 4 min and
      solid-liquid ratio of 1:10 was shown to be the optimum. Glucose showed a great
      advantage over xylose, and higher glucose content was more conducive to
      biobutanol production. However, the yield of solvent decreased with the increased
      initial sugar concentration. Considering comprehensively, 100 g/L initial glucose
      was considered to be the optimum. CONCLUSIONS: This work demonstrated an
      effective approach of improved butanol fermentation and its probable mechanisms
      of this positive effect, i.e. the adsorption of ABE solvent and the adhesion of
      bacteria on porous substrate accounted for the production improvement and the
      proportional variation of solvent constituents.

PMID- 23971992
TI  - Conditional and constitutive expression of a Tbx1-GFP fusion protein in mice.
AB  - BACKGROUND: Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS) is caused by
      a 1.5-3 Mb microdeletion of chromosome 22q11.2, frequently referred to as 22q11.2
      deletion syndrome (22q11DS). This region includes TBX1, a T-box transcription
      factor gene that contributes to the etiology of 22q11DS. The requirement for TBX1
      in mammalian development is dosage-sensitive, such that loss-of-function (LOF)
      and gain-of-function (GOF) of TBX1 in both mice and humans results in disease
      relevant congenital malformations. RESULTS: To further gain insight into the role
      of Tbx1 in development, we have targeted the Rosa26 locus to generate a new GOF
      mouse model in which a Tbx1-GFP fusion protein is expressed conditionally using
      the Cre/LoxP system. Tbx1-GFP expression is driven by the endogenous Rosa26
      promoter resulting in ectopic and persistent expression. Tbx1 is pivotal for
      proper ear and heart development; ectopic activation of Tbx1-GFP in the otic
      vesicle by Pax2-Cre and Foxg1-Cre represses neurogenesis and produces
      morphological defects of the inner ear. Overexpression of a single copy of Tbx1
      GFP using Tbx1Cre/+ was viable, while overexpression of both copies resulted in
      neonatal lethality with cardiac outflow tract defects. We have partially rescued
      inner ear and heart anomalies in Tbx1Cre/- null embryos by expression of Tbx1
      GFP. CONCLUSIONS: We have generated a new mouse model to conditionally
      overexpress a GFP-tagged Tbx1 protein in vivo. This provides a useful tool to
      investigate in vivo direct downstream targets and protein binding partners of
      Tbx1.

PMID- 23971994
TI  - Electrochemical evidence of intramolecular electronic communication in Zr and Hf
      phthalocyanines bearing ferrocene-containing beta-diketonato axial ligands:
      structure of [PcHf(FcCOCHCOC6H5)2].
AB  - The series of zirconium(IV) and hafnium(IV) phthalocyanine complexes
      [PcM(FcCOCHCOR)2] (Pc = phthalocyaninato; M = Zr; R = CF3 (1), CH3 (2), C6H5 (3),
      Fc ((C5H5)Fe(C5H4), 4), as well as M = Hf ; R = CF3 (5), CH3 (6), C6H5 (7), and
      Fc (8)) were synthesized. A single-crystal X-ray diffraction analysis of the
      structure of [PcHf(FcCOCHCOC6H5)2], 7 (Z = 2, space group P1), showed the two
      axial beta-diketonato ligands were orientated in such a way that the ferrocenyl
      groups were positioned diagonally opposite each other. From the structural
      determination of 7 it was clear that these complexes have a distorted D4h
      symmetry at the coordination site of the metal centers, which explains a
      splitting of the UV-vis Q band into Qx and Qy components with 3 <=
      Deltalambda(max,Q) <= 10 nm. Cyclic and square wave voltammetric studies in
      CH2Cl2/[N((n)Bu)4][B(C6F5)4] allowed observation of at least three
      phthalocyaninato macrocycle-based redox couples as well as all (i.e., two or
      four) well-resolved ferrocenyl couples in 1-8. For M = Zr and R = Fc, formal
      reduction potentials of the four ferrocenyl groups were found to be E degrees ' =
      296, 386, 538, and 687 mV versus free ferrocene. Spectroelectrochemical evidence,
      UV-vis Q-band maximum wavelengths, and HOMO-LUMO energy gaps as expressed by
      DeltaE degrees 'I-III = DeltaE degrees 'wave I - DeltaE degrees 'wave III were
      mutually consistent, indicating that the first phthalocyaninato ring-based
      oxidation occurs before ferrocenyl oxidations take place. The potential for each
      redox process was found to be dependent on the sum of beta-diketonato R-group
      group electronegativities, SigmachiR. Mathematical relationships for the
      dependency of E degrees ' on SigmachiR for all four observed ring-based redox
      processes as well as for the ferrocenyl-based redox processes were determined.
      This allowed prediction of potentials for redox processes that fall outside the
      workable potential window of the solvent. No significant differences were found
      between the corresponding redox potentials of zirconium and hafnium analogues
      bearing the same axial ligands.

PMID- 23971996
TI  - Development of family medicine in Ukraine.
AB  - This article includes a personal history of a family physician working in
      Ukraine. In June 2012, Pavlo Kolesnyk, Ukrainian Assistant Professor and a Family
      Doctor was awarded the second Montegute Scholar grant and had the chance to
      attend the Wonca Europe Conference 2012 in Vienna. In many developed countries,
      family medicine is already well established. In Ukraine, which has the legacy of
      a socialist health care system the implementation of the discipline started only
      at the end of the last century. The changes in the health care system were of
      greater importance in primary care and family medicine. It gave greater
      decentralization of the health care system and supported investment in primary
      care. This article describes the development of family medicine in undergraduate
      and postgraduate education. Whilst family medicine is officially a priority of
      health care policy, there is still a long process ahead. Family medicine needs
      financial support from the government and doctor's wages have to be increased, to
      prevent this branch of medicine being unpopular among graduating medical
      students.

PMID- 23971995
TI  - A valid strategy for precise identifications of transcription factor binding
      sites in combinatorial regulation using bioinformatic and experimental
      approaches.
AB  - BACKGROUND: Transcription factor (TF) binding sites (cis element) play a central
      role in gene regulation, and eukaryotic organisms frequently adapt a
      combinatorial regulation to render sophisticated local gene expression patterns.
      Knowing the precise cis element on a distal promoter is a prerequisite for
      studying a typical transcription process; however, identifications of cis
      elements have lagged behind those of their associated trans acting TFs due to
      technical difficulties. Consequently, gene regulations via combinatorial TFs, as
      widely observed across biological processes, have remained vague in many cases.
      RESULTS: We present here a valid strategy for identifying cis elements in
      combinatorial TF regulations. It consists of bioinformatic searches of available
      databases to generate candidate cis elements and tests of the candidates using
      improved experimental assays. Taking the MYB and the bHLH that collaboratively
      regulate the anthocyanin pathway genes as examples, we demonstrate how candidate
      cis motifs for the TFs are found on multi-specific promoters of chalcone synthase
      (CHS) genes, and how to experimentally test the candidate sites by designing DNA
      fragments hosting the candidate motifs based on a known promoter (us1 allele of
      Ipomoea purpurea CHS-D in our case) and applying site-mutagenesis at the motifs.
      It was shown that TF-DNA interactions could be unambiguously analyzed by assays
      of electrophoretic mobility shift (EMSA) and dual-luciferase transient
      expressions, and the resulting evidence precisely delineated a cis element. The
      cis element for R2R3 MYBs including Ipomoea MYB1 and Magnolia MYB1, for instance,
      was found to be ANCNACC, and that for bHLHs (exemplified by Ipomoea bHLH2 and
      petunia AN1) was CACNNG. A re-analysis was conducted on previously reported
      promoter segments recognized by maize C1 and apple MYB10, which indicated that
      cis elements similar to ANCNACC were indeed present on these segments, and tested
      positive for their bindings to Ipomoea MYB1. CONCLUSION: Identification of cis
      elements in combinatorial regulation is now feasible with the strategy outlined.
      The working pipeline integrates the existing databases with experimental
      techniques, providing an open framework for precisely identifying cis elements.
      This strategy is widely applicable to various biological systems, and may enhance
      future analyses on gene regulation.

PMID- 23971997
TI  - Promoting exercise in patients with depression: lessons learned from a brief
      educational intervention.
AB  - INTRODUCTION: Depression is a leading cause of disability worldwide. It is
      recommended that exercise is incorporated into the management of patients with
      depression, but it is not clear how best to implement this recommendation in
      clinical practice. OBJECTIVE: The objective of this study was to evaluate a
      pragmatic educational intervention promoting exercise to a group of patients
      diagnosed with depression, in a community setting. METHODS: Participants were
      convenience sampled from community based psychiatry clinics. WHO 5 Wellbeing and
      International Physical Activity Questionnaire scores were measured for each
      participant at baseline, and again three months after receiving the educational
      intervention on exercise. Open ended questions were used to elicit participants'
      beliefs and barriers to exercise and responses were thematically analysed.
      RESULTS: Thirty-five patients with depression were enrolled. Three months after
      the educational intervention, there were no significant changes in patients'
      activity levels or well-being scores (P > 0.05). Participants' responses to open
      ended questions revealed their varied, and often contradictory, beliefs on
      physical activity and exercise. Following from this, their suggestions on ways to
      improve the uptake of exercise advice highlighted the need for an individualized
      approach, with persistent patient encouragement and positive reinforcement.
      CONCLUSION: This study has generated valuable information on how to improve the
      promotion of exercise to patients with depression. Advice framed in a positive
      light, with persistent encouragement and tailoring to individual circumstances,
      is desired by patients to support their behavioural change.

PMID- 23971999
TI  - Chemical speciation of metal complexes from chemical shift calculations: the
      interaction of 2-amino-N-hydroxypropanamide with V(V) in aqueous solution.
AB  - The chemical speciation of 2-amino-N-hydroxypropanamide (beta-alaninohydroxamic
      acid, HL) and vanadium (V) in aqueous solution has been investigated through
      calculations of the thermodynamic properties and the (51)V nuclear magnetic
      resonance (NMR) chemical shifts of the species formed at equilibrium. The results
      have been compared directly with the experimental (51)V NMR data. The (51)V NMR
      chemical shifts have been calculated by using a density functional theory (DFT)
      approach accounting for relativistic corrections and solvent effects. All
      tautomers of the 1:1 and 1:2 VO2(+)/beta-ala complexes with different degrees of
      protonation have been calculated and thermodynamic and structural properties are
      presented for the most stable species. The system is better modeled as tautomeric
      equilibria, and species lying down in the range of 10 kcal.mol(-1) cannot be
      neglected at the BP/TZ2P/COSMO approach. In fact, the metal complex speciation in
      aqueous solution should not be investigated based solely on the thermodynamic
      analysis, but together with spectroscopic calculations such as NMR. 

PMID- 23971998
TI  - MicroRNA-510 promotes cell and tumor growth by targeting peroxiredoxin1 in breast
      cancer.
AB  - INTRODUCTION: MicroRNAs are small non-coding RNAs that are involved in the post
      transcriptional negative regulation of mRNAs. MicroRNA 510 (miR-510) was
      initially shown to have a potential oncogenic role in breast cancer by the
      observation of its elevated levels in human breast tumor samples when compared to
      matched non-tumor samples. Few targets have been identified for miR-510. However,
      as microRNAs function through the negative regulation of their direct targets,
      the identification of those targets is critical for the understanding of their
      functional role in breast cancer. METHODS: Breast cancer cell lines were
      transfected with pre-miR-510 or antisense miR-510 and western blotting and
      quantitative real time PCR were performed. Functional assays performed included
      cell growth, migration, invasion, colony formation, cytotoxicity and in vivo
      tumor growth. We performed a PCR assay to identify novel direct targets of miR
      510. The study focused on peroxiredoxin 1 (PRDX1) as it was identified through
      our screen and was bioinformatically predicted to contain a miR-510 seed site in
      its 3' untranslated region (3'UTR). Luciferase reporter assays and site-directed
      mutagenesis were performed to confirm PRDX1 as a direct target. The Student's two
      sided, paired t-test was used and a P-value less than 0.05 was considered
      significant. RESULTS: We show that miR-510 overexpression in non-transformed and
      breast cancer cells can increase their cell growth, migration, invasion and
      colony formation in vitro. We also observed increased tumor growth when miR-510
      was overexpressed in vivo. We identified PRDX1 through a novel PCR screen and
      confirmed it as a direct target using luciferase reporter assays. The
      reintroduction of PRDX1 into breast cancer cell lines without its regulatory
      3'UTR confirmed that miR-510 was mediating its migratory phenotype at least in
      part through the negative regulation of PRDX1. Furthermore, the PI3K/Akt pathway
      was identified as a positive regulator of miR-510 both in vitro and in vivo.
      CONCLUSIONS: In this study, we provide evidence to support a role for miR-510 as
      a novel oncomir. We show that miR-510 directly binds to the 3'UTR of PRDX1 and
      blocks its protein expression, thereby suppressing migration of human breast
      cancer cells. Taken together, these data support a pivotal role for miR-510 in
      breast cancer progression and suggest it as a potential therapeutic target in
      breast cancer patients.

PMID- 23972000
TI  - Systemic factors influence the prognosis of diabetic macular edema after pars
      plana vitrectomy with internal limiting membrane peeling.
AB  - PURPOSE/AIMS: To evaluate the prognostic factors for the best corrected visual
      acuity (BCVA) and central subfield macular thickness (CSMT) after vitrectomy with
      internal limiting membrane (ILM) peeling for diabetic macular edema. MATERIALS
      AND METHODS: A total of 44 eyes of 35 patients who had undergone vitrectomy with
      ILM peeling between March 2008 and September 2009 were examined. The
      relationships between preoperative systemic or ocular factors and BCVA or CSMT
      were evaluated before and at 6 months after the surgical procedure. RESULTS: Mean
      logarithm of the minimum angle of resolution improved from 0.74 +/- 0.35 (mean +/
      SD) preoperatively to 0.55 +/- 0.4 at 6 months postoperatively (p = 0.001).
      There was a significant improvement of the CSMT from 482 +/- 116 MUm before the
      operation to 355 +/- 126 MUm 6 months after the operation (p < 0.0001). The
      preoperative CSMT was significantly thicker with ischemic disease (p = 0.0016).
      Preoperative BCVA was significantly lower when subfoveal hard exudate was present
      (p = 0.0005). At the 6-month follow-up, CSMT was significantly thicker when there
      was a higher glycosylated hemoglobin (p = 0.008). BCVA at the 6-month follow-up
      was significantly lower in the group without any diabetes treatment history (p =
      0.0075) prior to the diagnosis of diabetic retinopathy. CONCLUSIONS: While BCVA
      and CSMT were associated with ocular factors before surgery, they were associated
      with glycemic control postoperatively. Glycemic control may be important for
      retinal thickness after ocular surgery.

PMID- 23972001
TI  - A systematic review of evidence on the association between hospitalisation for
      chronic disease related ambulatory care sensitive conditions and primary health
      care resourcing.
AB  - BACKGROUND: Primary health care is recognised as an integral part of a country's
      health care system. Measuring hospitalisations, that could potentially be avoided
      with high quality and accessible primary care, is one indicator of how well
      primary care services are performing. This review was interested in the
      association between chronic disease related hospitalisations and primary health
      care resourcing. METHODS: Studies were included if peer reviewed, written in
      English, published between 2002 and 2012, modelled hospitalisation as a function
      of PHC resourcing and identified hospitalisations for type 2 diabetes as a study
      outcome measure. Access and use of PHC services were used as a proxy for PHC
      resourcing. Studies in populations with a predominant user pay system were
      excluded to eliminate patient financial barriers to PHC access and utilisation.
      Articles were systematically excluded based on the inclusion criteria, to arrive
      at the final set of studies for review. RESULTS: The search strategy identified
      1778 potential articles using EconLit, Medline and Google Scholar databases. Ten
      articles met the inclusion criteria and were subject to review. PHC resources
      were quantified by workforce (either medical or nursing) numbers, number of
      primary care episodes, service availability (e.g. operating hours), primary care
      practice size (e.g. single or group practitioner practice--a larger practice has
      more care disciplines onsite), or financial incentive to improve quality of
      diabetes care. The association between medical workforce numbers and ACSC
      hospitalisations was mixed. Four of six studies found that less patients per
      doctor was significantly associated with a decrease in ambulatory care sensitive
      hospitalisations, one study found the opposite and one study did not find a
      significant association between the two. When results were categorised by PHC
      access (e.g. GPs/capita, range of services) and use (e.g. n out-patient visits),
      better access to quality PHC resulted in fewer ACSC hospitalisations. This
      finding remained when only studies that adjusted for health status were
      categorised. Financial incentives to improve the quality of diabetes care were
      associated with less ACSC hospitalisations, reported in one study. CONCLUSION:
      Seven of 12 measures of the relationship between PHC resourcing and ACSC
      hospitalisations had a significant inverse association. As a collective body of
      evidence the studies provide inconclusive support that more PHC resourcing is
      associated with reduced hospitalisation for ACSC. Characteristics of improved or
      increased PHC access showed inverse significant associations with fewer ACSC
      hospitalisations after adjustment for health status. The varied measures of
      hospitalisation, PHC resourcing, and health status may contribute to inconsistent
      findings among studies and make it difficult to interpret findings.

PMID- 23972003
TI  - Electrochemistry of aqueous pyridinium: exploration of a key aspect of
      electrocatalytic reduction of CO2 to methanol.
AB  - The mechanism by which pyridinium (pyrH(+)) is reduced at a Pt electrode is a
      matter of recent controversy. The quasireversible cyclic voltammetric wave
      observed at -0.58 V vs SCE at a Pt electrode was originally proposed to
      correspond to reduction of pyrH(+) to pyridinyl radical (pyrH(*)). This
      mechanistic explanation for the observed electrochemistry seems unlikely in light
      of recent quantum mechanical calculations that predict a very negative reduction
      potential (-1.37 V vs SCE) for the formation of pyrH(*). Several other mechanisms
      have been proposed to account for the discrepancy in calculated and observed
      reduction potentials, including surface adsorption of pyrH(*), reduction of
      pyrH(+) by two electrons rather than one, and reduction of the pyrH(+) proton to
      a surface hydride rather than a pi-based radical product. This final mechanism,
      which can be described as inner-sphere reduction of pyrH(+) to form a surface
      hydride, is consistent with experimental observations. 

PMID- 23972004
TI  - Variability of on-treatment platelet reactivity in patients on clopidogrel.
AB  - Response to clopidogrel therapy is subject to inter-individual variability.
      However, data with regard to on-treatment platelet reactivity over time in
      patients undergoing coronary stenting are scarce. For this prospective
      observational study, 102 consecutive patients on dual antiplatelet therapy
      undergoing coronary stenting due to stable coronary artery disease (CAD; n = 29),
      non ST-elevation acute coronary syndrome (NSTE-ACS; n = 45) and ST-elevation
      myocardial infarction (STEMI; n = 28) were enrolled. Vasodilator-stimulated
      phosphoprotein-phosphorylation assay was performed at baseline, as well as 1, 3
      and 6 months thereafter. Platelet reactivity index (PRI) measured after 1, 3 and
      6 months was lower compared to baseline values (p < 0.001). Variables responsible
      for reduced response to clopidogrel at baseline (reticulated platelet fraction,
      simvastatin therapy) and during steady-state phase (body mass index, blood
      glucose concentrations, cholesterol/HDL-ratio and quality of life score) were
      different. High on-treatment platelet reactivity (HTPR)-phenotype (cut-off = 50%
      PRI) within the first month changed in 31% of stable CAD, 33% of NSTE-ACS and 39%
      of STEMI patients, respectively. HTPR-phenotype in the steady-state phase (month
      1 to 6) changed in 45% of stable CAD, 33% of NSTE-ACS and 25% of STEMI patients.
      Response to clopidogrel and accordingly platelet function might vary over time,
      especially when a cut-off based approach, is used. There was a significant
      reduction of on-treatment platelet reactivity within the first month after
      percutaneous coronary intervention with stenting which was maintained for up to 6
      months. Variables associated with reduced response to clopidogrel at baseline and
      during steady-state phase were different, as the latter mainly reflected an
      unfavorable metabolic profile, comprising elevated BMI, blood glucose levels as
      well as cholesterol/HDL-ratio.

PMID- 23972002
TI  - Comparison of antibodies that mediate HIV type 1 gp120 antibody-dependent cell
      mediated cytotoxicity in asymptomatic HIV type 1-positive men and women.
AB  - Recent studies suggest that HIV-specific antibody-dependent cell-mediated
      cytotoxicity (ADCC) antibodies contribute to protective immunity against HIV. An
      important characteristic of future HIV vaccines will, therefore, be the ability
      to stimulate production of these antibodies in both men and women. Early studies
      suggest that men may have a better ADCC antibody response against HIV than women.
      Our objective was to determine whether men and women differ with respect to their
      ADCC response to HIV-1 gp120. HIV-positive, asymptomatic untreated men and women
      were matched for race, age, CD4(+) T cell number, HIV-1 viral load, and treatment
      and HIV-1 gp120 ADCC antibody titers were compared. A standard (51)Cr-release
      assay was used to determine HIV-1 gp120 ADCC antibody titers in HIV-1
      seropositive individuals from the Multicenter AIDS Cohort Study (MACS; n=32) and
      the Women's Interagency HIV Study (WIHS; n=32). Both sexes had high ADCC titers
      against HIV-1 gp120: 34.4% (n=11) and 40.6% (n=13) of men and women,
      respectively, had titers of 10,000; 62.5% (n=20) and 56.3% (n=18) had titers of
      100,000. Groups did not differ in percent specific release (% SR), lytic units
      (LU), correlations of titer to viral load, or titer to CD4(+) T cells in men or
      women. Both groups also had similar cross-clade ADCC antibody responses (p>0.5
      for % SR and LU). Comparable groups of asymptomatic HIV-1-infected men and women
      had comparable HIV-1 gp120 ADCC antibodies. Both sexes had significant cross
      clade reactivity. Differences between men and women may become evident as disease
      progresses; this should be evaluated at later stages of HIV-1 infection.

PMID- 23972006
TI  - Neurotrophic paths in the treatment of depression.

PMID- 23972005
TI  - Deamination of 6-aminodeoxyfutalosine in menaquinone biosynthesis by distantly
      related enzymes.
AB  - Proteins of unknown function belonging to cog1816 and cog0402 were characterized.
      Sav2595 from Steptomyces avermitilis MA-4680, Acel0264 from Acidothermus
      cellulolyticus 11B, Nis0429 from Nitratiruptor sp. SB155-2 and Dr0824 from
      Deinococcus radiodurans R1 were cloned, purified, and their substrate profiles
      determined. These enzymes were previously incorrectly annotated as adenosine
      deaminases or chlorohydrolases. It was shown here that these enzymes actually
      deaminate 6-aminodeoxyfutalosine. The deamination of 6-aminodeoxyfutalosine is
      part of an alternative menaquinone biosynthetic pathway that involves the
      formation of futalosine. 6-Aminodeoxyfutalosine is deaminated by these enzymes
      with catalytic efficiencies greater than 10(5) M(-1) s(-1), Km values of 0.9-6.0
      MUM, and kcat values of 1.2-8.6 s(-1). Adenosine, 2'-deoxyadenosine,
      thiomethyladenosine, and S-adenosylhomocysteine are deaminated at least an order
      of magnitude slower than 6-aminodeoxyfutalosine. The crystal structure of Nis0429
      was determined and the substrate, 6-aminodeoxyfutalosine, was positioned in the
      active site on the basis of the presence of adventitiously bound benzoic acid. In
      this model, Ser-145 interacts with the carboxylate moiety of the substrate. The
      structure of Dr0824 was also determined, but a collapsed active site pocket
      prevented docking of substrates. A computational model of Sav2595 was built on
      the basis of the crystal structure of adenosine deaminase and substrates were
      docked. The model predicted a conserved arginine after beta-strand 1 to be
      partially responsible for the substrate specificity of Sav2595. 

PMID- 23972007
TI  - Management strategies for SSRI-induced sexual dysfunction.

PMID- 23972008
TI  - Antidepressant effects of botulinum toxin A: scientific rationale.

PMID- 23972009
TI  - Antidepressant effects of botulinum toxin A: scientific rationale; author
      response.

PMID- 23972010
TI  - Cardiovascular involvements in HIV-infected patients.
AB  - The lifespan of HIV-infected patients is increasing, and cardiovascular diseases
      becoming a major comorbidity and leading cause of death in this population due to
      high prevalence of the cardiac risk factors and possibly due to the use of
      antiretroviral therapy. Aggressive reduction of these risk factors and treatment
      of cardiovascular diseases are crucial to decrease the cardiovascular mortality
      in these patients. 

PMID- 23972012
TI  - Mimicking bone nanostructure by combining block copolymer self-assembly and 1D
      crystal nucleation.
AB  - The orientation and spatial distribution of nanocrystals in the organic matrix
      are two distinctive structural characteristics associated with natural bone.
      Synthetic soft materials have been used to successfully control the orientation
      of mineral crystals. The spatial distribution of minerals in a synthetic
      scaffold, however, has yet to be reproduced in a biomimetic manner. Herein, we
      report using block copolymer-decorated polymer nanofibers to achieve
      biomineralized fibrils with precise control of both mineral crystal orientation
      and spatial distribution. Exquisite nanoscale structural control in biomimetic
      hybrid materials has been demonstrated. 

PMID- 23972011
TI  - Erythropoietin improved cognitive function and decreased hippocampal caspase
      activity in rat pups after traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a leading cause of acquired neurologic disability
      in children. Erythropoietin (EPO), an anti-apoptotic cytokine, improved cognitive
      outcome in adult rats after TBI. To our knowledge, EPO has not been studied in a
      developmental TBI model. HYPOTHESIS: We hypothesized that EPO would improve
      cognitive outcome and increase neuron fraction in the hippocampus in 17-day-old
      (P17) rat pups after controlled cortical impact (CCI). METHODS: EPO or vehicle
      was given at 1, 24, and 48 h after CCI and at post injury day (PID) 7. Cognitive
      outcome at PID14 was assessed using Novel Object Recognition (NOR). Hippocampal
      EPO levels, caspase activity, and mRNA levels of the apoptosis factors Bcl2, Bax,
      Bcl-xL, and Bad were measured during the first 14 days after injury. Neuron
      fraction and caspase activation in CA1, CA3, and DG were studied at PID2.
      RESULTS: EPO normalized recognition memory after CCI. EPO blunted the increased
      hippocampal caspase activity induced by CCI at PID1, but not at PID2. EPO
      increased neuron fraction in CA3 at PID2. Brain levels of exogenous EPO appeared
      low relative to endogenous. Timing of EPO administration was associated with
      temporal changes in hippocampal mRNA levels of EPO and pro-apoptotic factors.
      Conclusion/Speculation: EPO improved recognition memory, increased regional
      hippocampal neuron fraction, and decreased caspase activity in P17 rats after
      CCI. We speculate that EPO improved cognitive outcome in rat pups after CCI as a
      result of improved neuronal survival via inhibition of caspase-dependent
      apoptosis early after injury.

PMID- 23972014
TI  - Two new dammarane-type glycosides from Phlomis umbrosa.
AB  - Two new dammarane-type glycosides, phlomisumbroside A (1) and phlomisumbroside B
      (2), together with 15 known compounds (3-17) were isolated from the leaves of
      Phlomis umbrosa Turcz. Their structures were established by the spectroscopic
      methods including 2D NMR techniques. 

PMID- 23972013
TI  - Efficacy of an imidacloprid/flumethrin collar against fleas, ticks and tick-borne
      pathogens in dogs.
AB  - BACKGROUND: Tick-borne diseases comprise a group of maladies that are of
      substantial medical and veterinary significance. A range of tick-borne pathogens,
      including diverse species of bacteria and protozoa, can infect both dogs and
      humans. Hence, the control of tick infestations is pivotal to decrease or prevent
      tick-borne pathogen transmission. Therefore, different commercial products with
      insecticidal, repellent or both properties have been developed for use on dogs.
      Recently, a collar containing a combination of imidacloprid 10% and flumethrin
      4.5% has proven effective to prevent tick and flea infestations in dogs under
      field conditions and the infection by some vector-borne pathogens they transmit
      under laboratory-controlled conditions. METHODS: From March 2011 to April 2012, a
      field study was conducted in a private shelter in southern Italy to assess the
      efficacy of the imidacloprid/flumethrin collar against tick and flea infestations
      and to determine if this strategy would decrease tick-borne pathogen transmission
      in young dogs. A total of 122 animals were enrolled in the study and randomly
      assigned to group A (n = 64; collared) or group B (n = 58; untreated controls).
      Dogs were examined monthly for ticks and fleas and systematically tested for
      selected tick-borne pathogens. RESULTS: Compared to controls, the collar provided
      overall efficacies of 99.7% and 100% against tick and flea infestation,
      respectively. The overall efficacy for the prevention of tick-borne pathogens
      (i.e., Anaplasma platys and Babesia vogeli) was 91.6%. CONCLUSIONS: This study
      demonstrates that the imidacloprid/flumethrin collar is efficacious against flea
      and tick infestation as well as tick-borne pathogen transmission to dogs under
      field conditions.

PMID- 23972016
TI  - Differences in insect resistance between tomato species endemic to the Galapagos
      Islands.
AB  - BACKGROUND: The Galapagos Islands constitute a highly diverse ecosystem and a
      unique source of variation in the form of endemic species. There are two endemic
      tomato species, Solanum galapagense and S. cheesmaniae and two introduced tomato
      species, S. pimpinellifolium and S. lycopersicum. Morphologically the two endemic
      tomato species of the Galapagos Islands are clearly distinct, but molecular
      marker analysis showed no clear separation. Tomatoes on the Galapagos are
      affected by both native and exotic herbivores. Bemisia tabaci is an important
      introduced insect species that feeds on a wide range of plants. In this article,
      we address the question whether the differentiation between S. galapagense and S.
      cheesmaniae may be related to differences in susceptibility towards phloem
      feeders and used B. tabaci as a model to evaluate this. RESULTS: We have
      characterized 12 accessions of S. galapagense, 22 of S. cheesmaniae, and one of
      S. lycopersicum as reference for whitefly resistance using no-choice experiments.
      Whitefly resistance was found in S. galapagense only and was associated with the
      presence of relatively high levels of acyl sugars and the presence of glandular
      trichomes of type I and IV. Genetic fingerprinting using 3316 SNP markers did not
      show a clear differentiation between the two endemic species. Acyl sugar
      accumulation as well as the climatic and geographical conditions at the
      collection sites of the accessions did not follow the morphological species
      boundaries. CONCLUSION: Our results suggest that S. galapagense and S.
      cheesmaniae might be morphotypes rather than two species and that their co
      existence is likely the result of selective pressure.

PMID- 23972018
TI  - The cerebellum and motor learning.
AB  - People with profound memory deficits can acquire new motor skills, even though on
      each day of training they may be unaware of having seen the training apparatus
      before. Similarly, rabbits can acquire or retain a conditioned nictitating
      membrane response despite massive lesions of the hippocampus or the cerebral
      cortex. Both lines of evidence suggest that sub-cortical structures may be
      sufficient for many forms of motor learning. One possible locus for motor
      learning is the cerebellum. This article traces the history of our knowledge of
      structure and function of the cerebellum. The anatomical and physiological
      evidence demonstrates that the cerebellum has the neural connections necessary to
      mediate simple forms of motor learning or reflex plasticity. Behavioral studies
      demonstrate that the cerebellum is involved in modification of the
      vestibuloocular reflex, recalibration of saccadic eye movements, and acquisition
      of the conditioned nictitating membrane response. Although the evidence in all
      three instances suggests that the cerebellum is important, there is no agreement
      as to whether the cerebellum is always necessary for motor learning or how it
      might participate. Two views are presented: one supporting the idea of the
      cerebellum as the locus for motor learning and the other opposing this idea. Some
      evidence that might resolve these disagreements is discussed. 

PMID- 23972017
TI  - Short communication: Evidence that microbial translocation occurs in HIV-infected
      children in the United Kingdom.
AB  - Microbial translocation (MT) from the gut is implicated in driving immune
      activation, increasing morbidity and mortality in HIV. We used bacterial 16S rDNA
      PCR, Sanger sequencing, and high-throughput sequencing to identify microbial DNA
      in the bloodstream of HIV-infected children in London, United Kingdom. Blood
      samples were collected from sequential children attending the HIV clinic at Great
      Ormond Street Hospital, London. DNA extraction, broad range 16S rDNA PCR, and
      standard Sanger sequencing were carried out. A subset of positive samples was
      analyzed by high-throughput sequencing (Roche 454 platform). Of 105 samples
      collected from sequential children, nine were positive using broad range 16S rDNA
      PCR (8.6%; 95% CI 4.4-16%). From three amplicons, 16S rDNA sequences were
      identified as Streptococcus, Propionibacterium acnes, and coagulase-negative
      Staphylococcus. Four positive samples were analyzed by high-throughput
      sequencing. In the three samples in which organisms were identified by Sanger
      sequencing, the same species were identified. Further species, in differing
      proportions, were identified in all four samples. The identified organisms
      included known gut orders Bifidobacteriaceae, Lactobacillaceae, Bacteroidales,
      and Clostridiales. In immunocompetent children of equivalent age, no bacterial
      DNA was detected in blood using this approach. This is the first study to our
      knowledge using molecular techniques to identify MT in children in the developed
      world. Our data indicate that 16S rDNA is detectable in 8.6% of HIV-infected
      children. Levels of DNA were low and from multiple bacterial species. Further
      studies are needed to ascertain the importance of MT in HIV-infected children.

PMID- 23972019
TI  - Cortical maturation and the development of visual attention in early infancy.
AB  - Bronson (1974) reviewed evidence in support of the claim that the development of
      visually guided behavior in the human infant over the first few months of life
      represents a shift from subcortical to cortical visual processing. Recently, this
      view has been brought into question for two reasons; first, evidence revealing
      apparently sophisticated perceptual abilities in the newborn, and second,
      increasing evidence for multiple cortica streams of visual processing. The
      present paper presents a reanalysis of the relation between the maturation of
      cortical pathways and the development of visually guided behavior, focusing in
      particular on how the maturational state of the primary visual cortex may
      constrain the functioning of neural pathways subserving oculomotor control. 

PMID- 23972020
TI  - On the interaction of selective attention and lexical knowledge: a connectionist
      account of neglect dyslexia.
AB  - Neglect dyslexia, a reading impairment acquired as a consequence of brain injury,
      is traditionally interpreted as a disturbance of selective attention. Patients
      with neglect dyslexia may ignore the left side of an open book, the beginning
      words of a line of text, or the beginning letters of a single word. These
      patients provide a rich but sometimes contradictory source of data regarding the
      locus of attentional selectivity. We have reconsidered the patient data within
      the framework of an existing connectionist model of word recognition and spatial
      attention. We show that the effects of damage to the model resemble the reading
      impairments observed in neglect dyslexia. In simulation experiments, we account
      for a broad spectrum of behaviors including the following: (1) when two
      noncontiguous stimuli are presented simultaneously, the contralesional stimulus
      is neglected (extinction); (2) explicit instructions to the patient can reduce
      the severity of neglect; (3) stimulus position in the visual field affects
      reading performance; (4) words are read much better than pronounceable nonwords;
      (5) the nature of error responses depends on the morphemic composition of the
      stimulus; and (6) extinction interacts with lexical knowledge (if two words are
      presented that form a compound, e.g., COW and BOY, the patient is more likely to
      report both than in a control condition, e.g., SUN and FLY). The convergence of
      findings from the neuropsychological research and the computational modeling
      sheds light on the role of attention in normal visuospatial processing,
      supporting a hybrid view of attentional selection that has properties of both
      early and late selection. 

PMID- 23972021
TI  - Modulation of Spontaneous Brain Activity during Mental Imagery.
AB  - Magnetic measurements of average power of human alpha and beta activity over the
      occipital and parietal areas of the scalp reveal spatially selective suppression
      of the activity of the occipital cortex when abstract figures are briefly
      presented visually and subjects simply indicate that they saw the figure.
      However, the duration of the suppression increases markedly when subjects must
      indicate whether or not they had previously seen the figure. The reaction time is
      similarly prolonged during the search of visual memory, and is commensurate with
      the duration of selective suppression of brain activity. It is also demonstrated
      that alpha activity is not replaced by beta activity during this suppression, but
      that power in the beta band is also diminished during memory search. Low
      correlations between the scalp distributions of power in the beta and alpha bands
      indicate that partly different neuronal populations give rise to activity of
      these different frequency bands. Since magnetic fields are negligibly affected by
      intervening bone tissues, dramatic asymmetries in the distribution of alpha
      activity across the scalps of individuals and the differences in distribution
      between individuals cannot be ascribed to differences in skull thickness but are
      due instead to differences in underlying brain anatomy or function. Nevertheless,
      a common pattern of suppression of alpha activity is observed across subjects
      during well-controlled cognitive tasks. This implies that the visual system is
      involved in mental imagery. 

PMID- 23972022
TI  - Effects of ibotenic lesions of mammillary bodies on spontaneous and rewarded
      spatial alternation in mice.
AB  - Previous experiments in our laboratory have shown that lesions of the mammillary
      bodies (MB) in mice induce memory deficits in spontaneous spatial alternation
      (SA) tasks. However, it has also been shown that performance on memory tasks by
      both humans and animals depends on the degree of effort involved in a given task.
      Thus, we hypothesized that the involvement of MB-damaged subjects in tasks that
      require more effortful processing than does SA might reduce their memory
      deficits. Accordingly, in the first experiment, the effects of MB lesions were
      studied in both an SA and a rewarded alternation (RA) task. Daily test sessions
      consisted of six successive trials separated by a short intertrial interval (ITI)
      of 30 sec, which allowed us to study interference (i.e., the deleterious effect
      of the first trials of a session on the performance on the last trials of a
      session). Results of the first experiment showed that the MB-lesioned subjects
      were impaired on their performance on the SA (they were more sensitive to
      interference than were controls) but not RA task. This finding is consistent with
      our hypothesis. In the second experiment, the ITI in the RA task was increased
      from 50 sec to 3 min. At the longer ITI (3 min), we found that the MB-lesioned
      subjects had the same deficit in performance that the MB-lesioned subjects had on
      the SA task at an ITI of 30 sec. Control mice also had a similar deficit in
      performance at the ITI of 5 min. We suggest that even in the RA task, the
      performance of MB-damaged subjects remains more sensitive to time-dependent
      interference than does the performance of controls. The significance of our study
      to the understanding of amnesia (especially Korsakoff's syndrome and frontal lobe
      pathology) is discussed. 

PMID- 23972023
TI  - Receptive field characteristics that allow parietal lobe neurons to encode
      spatial properties of visual input: a computational analysis.
AB  - A subset of visually sensitive neurons in the parietal lobe apparently can encode
      the locations of stimuli, whereas visually sensitive neurons in the
      inferotemporal cortex (area IT) cannot. This finding is puzzling because both
      sorts of neurons have large receptive fields, and yet location can be encoded in
      one case, but not in the other. The experiments reported here investigated the
      hypothesis that a crucial difference between the IT and parietal neurons is the
      spatial distribution of their response profiles. In particular, IT neurons
      typically respond maximally when stimuli are presented at the fovea, whereas
      parietal neurons do not. We found that a parallel-distributed-processing network
      could map a point in an array to a coordinate representation more easily when a
      greater proportion of its input units had response peaks off the center of the
      input array. Furthermore, this result did not depend on potentially implausible
      assumptions about the regularity of the overlap in receptive fields or the
      homogeneity of the response profiles of different units. Finally, the internal
      representations formed within the network had receptive fields resembling those
      found in area 7a of the parietal lobe. 

PMID- 23972024
TI  - Lesion analysis in neuropsychology.

PMID- 23972025
TI  - Effect of continuous statistically standardized measures of estrogen and
      progesterone receptors on disease-free survival in NCIC CTG MA.12 Trial and BC
      Cohort.
AB  - INTRODUCTION: We hypothesized improved inter-laboratory comparability of estrogen
      receptor (ER) and progesterone receptor (PgR) across different assay
      methodologies with adjunctive statistical standardization, akin to bone mineral
      density (BMD) z-scores. We examined statistical standardization in MA.12, a
      placebo-controlled pre-menopausal trial of adjuvant tamoxifen with locally
      assessed hormone receptor +/- tumours, and in a cohort of post-menopausal British
      Columbia (BC) tamoxifen-treated patients. METHODS: ER and PgR were centrally
      assessed for both patient groups with real time quantitative reverse
      transcription polymerase chain reaction (qPCR) and immunohistochemistry (IHC).
      Effects on disease-free survival (DFS) were investigated separately for 345 MA.12
      and 673 BC patients who had both qPCR and IHC assessments. Comparisons utilized
      continuous laboratory units and statistically standardized z-scores. Univariate
      categorization of ER/PgR was by number of standard deviations (SD) above or below
      the mean (z-score >=1.0 SD below mean; z-score <1.0 SD below mean; z-score <=1.0
      SD above mean; z-score >1.0 SD above mean). Exploratory multivariate examinations
      utilized step-wise Cox regression. RESULTS: Median follow-up for MA.12 was 9.7
      years; for BC patients, 11.8 years. For MA.12, 101 of 345 (29%) patients were IHC
      ER-PgR-. ER was not univariately associated with DFS (qPCR, P = 0.19; IHC, P =
      0.08), while PgR was (qPCR, P = 0.09; IHC, P = 0.04). For BC patients, neither
      receptor was univariately associated with DFS: for ER, PCR, P = 0.36, IHC, P =
      0.24; while for PgR, qPCR, P = 0.17, IHC, P = 0.31. Multivariately, MA.12
      patients randomized to tamoxifen had significantly better DFS (P = 0.002 to
      0.005) than placebo. Meanwhile, jointly ER and PgR were not associated with DFS
      whether assessed by qPCR or by IHC in all patients, or in the subgroup of
      patients with IHC positive stain, for pooled or separate treatment arms.
      Different results by type of continuous unit supported the concept of ER level
      being relevant for medical decision-making. For postmenopausal BC tamoxifen
      patients, higher qPCR PgR was weakly associated with better DFS (P = 0.06).
      CONCLUSIONS: MA.12 pre-menopausal patients in a placebo-controlled tamoxifen
      trial had similar multivariate prognostic effects with statistically standardized
      hormone receptors when tumours were assayed by qPCR or IHC, for hormone receptor
      +/- and + tumours. The BC post-menopausal tamoxifen cohort did not exhibit a
      significant prognostic association of ER or PgR with DFS. Adjunctive statistical
      standardization is currently under investigation in other NCIC CTG endocrine
      trials.

PMID- 23972026
TI  - The discriminating properties of an optoelectronic movement analysis method in
      patients with parkinsonism.
AB  - Several partly overlapping diseases have Parkinsonism as a symptom and tools that
      may differentiate between these disorders would be helpful. The authors evaluated
      the discriminating properties of the objective automated posturo-locomotor-manual
      (PLM) L-DOPA test in regard to health, and the movement disorders Parkinson's
      disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy
      (PSP). A PLM test-retest procedure was performed in healthy controls (n = 37) and
      results were compared with PLM L-DOPA tests performed by 132 patients with
      Parkinsonism in intermediate to advanced stages (56 PD, 53 MSA, 23 PSP). The
      movement time (MT) for the standardized movement and its different components was
      measured. The discriminating abilities of individual, or combinations of, test
      variables were determined by forward stepwise multiple logistic regression and
      evaluated with receiver-operating characteristic (ROC) analysis. Each PLM
      variable separated healthy persons from patients with Parkinsonism before
      administration of L-DOPA (area under the curve (AUC) = 0.94-0.99, p < .001 for
      any separate variable). A combination of (MToff - MTon)/MToff and MTon had the
      highest ability to separate patients with PD from patients with atypical
      Parkinsonism (area under the curve = 0.91, p < .001). The PLM test discriminates
      between healthy controls and patients with Parkinsonism, and between patients
      with Parkinson's disease and patients with atypical Parkinsonism.

PMID- 23972027
TI  - Implementing a training intervention to support caregivers after stroke: a
      process evaluation examining the initiation and embedding of programme change.
AB  - BACKGROUND: Medical Research Council (MRC) guidance identifies implementation as
      a key element of the development and evaluation process for complex healthcare
      interventions. Implementation is itself a complex process involving the
      mobilization of human, material, and organizational resources to change practice
      within settings that have pre-existing structures, historical patterns of
      relationships, and routinized ways of working. Process evaluations enable
      researchers and clinicians to understand how implementation proceeds and what
      factors impact on intended program change. A qualitative process evaluation of
      the pragmatic cluster randomized controlled trial; Training Caregivers after
      Stroke was conducted to examine how professionals were engaged in the work of
      delivering training; how they reached and involved caregivers for whom the
      intervention was most appropriate; how did those on whom training was targeted
      experience and respond to it. Normalization Process Theory, which focuses
      attention on implementing and embedding program change, was used as a sensitizing
      framework to examine selected findings. RESULTS: Contextual factors including
      organizational history and team relationships, external policy, and service
      development initiatives, impinged on implementation of the caregiver training
      program in unintended ways that could not have been predicted through focus on
      mechanisms of individual and collective action at unit level. Factors that
      facilitated or impeded the effectiveness of the cascade training model used,
      whether and how stroke unit teams made sense of and engaged individually and
      collectively with a complex caregiver training intervention, and what impact
      these factors had on embedding the intervention in routine stroke unit practice
      were identified. CONCLUSIONS: Where implementation of complex interventions
      depends on multiple providers, time needs to be invested in reaching agreement on
      who will take responsibility for delivery of specific components and in
      determining how implementation and its effectiveness will be monitored. This goes
      beyond concern with intervention fidelity; explicit consideration also needs to
      be given to the implementation process in terms of how program change can be
      effected at organizational, practice, and service delivery levels. Normalization
      Process Theory's constructs help identify vulnerable features of implementation
      processes in respect of the work involved in embedding complex interventions.

PMID- 23972028
TI  - Influence of axial length on peripapillary retinal nerve fiber layer thickness in
      children: a study by RTVue spectral-domain optical coherence tomography.
AB  - PURPOSE: To evaluate the influence of axial length on peripapillary retinal nerve
      fiber layer (RNFL) thickness in myopic, hyperopic and emmetropic children eyes by
      RTVue optical coherence tomography (OCT). METHODS: One hundred twenty eyes of 120
      children including 40 myopic, 40 emmetropic and 40 hyperopic eyes were enrolled
      in the study. Peripapillary RNFL thickness measurements were performed using
      spectral-domain RTVue OCT (Optovue, Fremont, CA). RNFL thickness parameters were
      obtained from all octametric sections: upper temporal (TU), superotemporal (ST),
      superonasal (SN), upper nasal (NU), lower nasal (NL), inferonasal (IN),
      inferotemporal (IT) and lower temporal (TL). Spherical equivalent refractive
      error was determined via cycloplegic auto-refraction (Topcon, Tokyo, Japan). The
      axial length was measured using IOLMaster (Carl Zeiss MEDITEC). Littmann formula
      was used for correction of axial length-related ocular magnification effect.
      RESULTS: Peripapillary RNFL thicknesses were significantly different among the
      three groups in all sectors except for NU and IT sectors. RNFL thicknesses in all
      sectors except for TU and TL sectors had significant negative correlations with
      axial length. However, these differences (excluding TU and TL sectors) and
      correlations disappeared after correction of magnification effect. CONCLUSION: In
      conclusion, axial length influences peripapillary RNFL thickness as measured by
      RTVue OCT. However, this appears to be due to the ocular magnification effects
      associated with axial length and can be corrected for with the application of the
      Littman formula.

PMID- 23972029
TI  - Could mean platelet volume among complete blood count parameters be a surrogate
      marker of metabolic syndrome in pre-pubertal children?
AB  - Interest in childhood metabolic syndrome (MetS) has increased substantially due
      to the increasing prevalence of childhood obesity on a global scale. Early
      recognition of MetS is critical in order to delay the development of
      cardiovascular disease (CVD). In this study, we evaluated the relationship
      between complete blood count (CBC) parameters and MetS among pre-pubertal
      children which may provide evidence in support of using low cost, readily
      available clinical haematological parameters for the detection of MetS. A
      retrospective analysis was carried out on 330 (125 lean vs. 205 overweight)
      Turkish pre-pubertal children who attend to a paediatric outpatient clinic. Age,
      gender, puberty, body mass index, CBC parameters, cardiometabolic risk factors
      including lipid profiles, high sensitive serum reactive protein (hsCRP) and
      insulin resistance index calculated by homeostasis model assessment (HOMA-IR)
      were evaluated and compared among lean, overweight children and children with
      MetS. The mean age of the study population was 7.4 +/- 1.9 years. In both gender,
      the mean values of mean corpuscular volume (MCV), mean corpuscular haemoglobin
      (MCH) and mean corpuscular haemoglobin concentration (MCHC) were significantly
      lower and red blood cell (RBC), platelet (PLT) counts were significantly higher
      in overweight children. Overall, 8.4% (n = 28) of patients met the criteria of
      MetS. Children with MetS had higher levels of PLT and lower levels of mean
      platelet volume (MPV). Of all the haematological parameters analysed, PLT was
      positively, whereas MPV was negatively correlated with MetS in girls. In
      addition, MPV was inversely correlated with fasting blood glucose, HOMA-IR, low
      density lipoprotein-cholesterol (LDL-C) and low density lipoprotein
      cholesterol/high density lipoprotein-cholesterol (LDL-C/HDL-C) ratio in girls
      after adjusting for confounding factors. The risk analyses of MetS in terms of
      MPV quartiles showed that the adjusted OR (95% CI) for the lowest vs. the highest
      quartile was 7.71 (1.45-40.89) in girls. These data might suggest that MPV could
      be another feature of MetS in pre-pubertal girls and might be used as a surrogate
      marker for MetS in clinical settings.

PMID- 23972030
TI  - Facile synthesis of dendritic gold nanostructures with hyperbranched
      architectures and their electrocatalytic activity toward ethanol oxidation.
AB  - Gold dendritic nanostructures with hyperbranched architectures were synthesized
      by the galvanic replacement reaction between nickel wire and HAuCl4 in aqueous
      solution. The study revealed that the morphology of the obtained nanostructures
      strongly depended on experimental parameters such as the HAuCl4 solution
      concentration, reaction temperature, and time, as well as stirring or not.
      According to the investigation of the growth process, it was proposed that gold
      nanoparticles with rough surfaces were first deposited on the nickel substrate
      and that subsequent growth preferentially occurred on the preformed gold
      nanoparticles, finally leading to the formation of hyperbranched gold dendrites
      via a self-organization process under nonequilibrium conditions. The
      electrochemical experiment results demonstrated that the as-obtained gold
      dendrites exhibited high catalytic activity toward ethanol electrooxidation in
      alkaline solution, indicating that this nanomaterial may be a potential catalyst
      for direct ethanol fuel cells. 

PMID- 23972031
TI  - The quality of life of people with epilepsy at a tertiary referral centre in
      Malaysia.
AB  - BACKGROUND: Epilepsy, a chronic disorder of brain characterised by a
      predisposition to generate epileptic seizures, has an effect on the psychosocial
      well-being of sufferers. Measuring the quality of life (QOL) of people with
      epilepsy (PWE) is increasingly recognized as an important component of clinical
      management. QOL measures differ between countries and there is limited
      information regarding PWE in Malaysia. The aim of this study was to determine the
      health related QOL and its relationship with the presence of seizures in PWE at a
      Malaysian tertiary referral center. METHODS: A total of 106 adults with epilepsy
      attending the weekly neurology clinic of Universiti Sains Malaysia Hospital were
      interviewed in this cross-sectional study. The QOL was measured using a validated
      Malay translated version of the Quality of Life in Epilepsy Scale-31 (QOLIE-31).
      Analysis of covariance was used for data analysis. RESULTS: The mean age was 31.8
      years old (standard deviation (SD) 11.0) and 56.6% were females. The mean total
      score of QOLIE-31was 68.9 (SD 15.9). The highest subscale score was the
      medication effects with a mean of 79.4 (SD 28.5) and the lowest was seizure worry
      with 47.5 (SD 25.0). Respondents who had one or more seizures in the past four
      weeks had significantly lower mean score of QOL [63.4, 95% CI: 59.2, 67.5] than
      those who had no seizure [mean score 73.5, 95% CI: 69.3, 77.9] after adjusting
      for age, sex, treatment, duration and age at onset of epilepsy [F test =11.215, p
      = 0.001, R2 = 0.159]. All the sub-scales of QOL showed significant moderate
      correlation with the frequency of seizures except for cognitive functioning.
      CONCLUSIONS: Worrying about seizure had the major contribution on QOL, while
      medication effect had the least. This study confirms the importance of seizure
      control for a better QOL in Malaysian patients with epilepsy.

PMID- 23972032
TI  - Study of the gammaD-crystallin protein using two-dimensional infrared (2DIR)
      spectroscopy: experiment and simulation.
AB  - Cataracts is a misfolding protein disease in which one of the major components is
      the gammaD-crystallin protein. The conformational structure of the aggregated
      gammaD-crystallin and the interactions that cause aggregation are largely
      unknown. A recent experimental two-dimensional infrared (2DIR) spectroscopy study
      determined that the C-terminal domain has a high propensity to form beta-sheets
      whereas the N-terminal domain forms a disordered structure in the fiber state. We
      present a combined computational molecular dynamics and infrared spectroscopy
      study of the local dynamics of these domains. The computed 2DIR signals agree
      remarkably well with experiment. We show that the two domains, both of which have
      a Greek key structural fold, experience different electrostatic environments,
      which may be related to the fact that the C-terminal domain is more structurally
      stable than the N-terminal domain. We correlate the vibrational couplings to
      known energy dissipation mechanisms and reveal their origin. 

PMID- 23972033
TI  - Topology of the yeast Ras converting enzyme as inferred from cysteine
      accessibility studies.
AB  - The Ras converting enzyme (Rce1p) is an endoprotease that is involved in the post
      translational processing of the Ras GTPases and other isoprenylated proteins. Its
      role in Ras biosynthesis marks Rce1p as an anticancer target. By assessing the
      chemical accessibility of cysteine residues substituted throughout the
      Saccharomyces cerevisiae Rce1p sequence, we have determined that yeast Rce1p has
      eight segments that are protected from chemical modification. Notably, the three
      residues that are essential for yeast Rce1p function (E156, H194, and H248) are
      all chemically inaccessible and associated with separate protected segments. By
      specifically assessing the chemical reactivity and glycosylation potential of the
      NH2 and COOH termini of Rce1p, we further demonstrate that Rce1p has an odd
      number of transmembrane spans. Substantial evidence that the most NH2-terminal
      segment functions as a transmembrane segment with the extreme NH2 terminus
      projecting into the endoplasmic reticulum (ER) lumen is presented. Because each
      of the remaining seven segments is too short to contain two spans and is flanked
      by chemically reactive positions, we infer that these segments are not
      transmembrane segments but rather represent compact structural features and/or
      hydrophobic loops that penetrate but do not fully span the bilayer (i.e., re
      entrant helices). We thus propose a topological model in which yeast Rce1p
      contains a single transmembrane helix localized at its extreme NH2 terminus and
      one or more re-entrant helices and/or compact structural domains that populate
      the cytosolic face of the ER membrane. Lastly, we demonstrate that the natural
      cysteine residues of Rce1p are chemically inaccessible and fully dispensable for
      in vivo enzyme activity, formally eliminating the possibility of a cysteine-based
      enzymatic mechanism for this protease.

PMID- 23972034
TI  - Molecular characterization of Trichinella spiralis aminopeptidase and its
      potential as a novel vaccine candidate antigen against trichinellosis in BALB/c
      mice.
AB  - BACKGROUND: Trichinella spiralis is an intracellular parasite that can cause a
      serious threat to human health by causing trichinellosis. The aminopeptidase (AP)
      was found in the proteins produced by T. spiralis infective larvae after in vitro
      co-culture with intestinal epithelial cells, but its characteristics and function
      are unknown. The purpose of this study was to identify the T. spiralis
      aminopeptidase (TsAP) and to investigate its potential as a vaccine candidate
      antigen against T. spiralis infection. METHODS: T. spiralis aminopeptidase (TsAP)
      gene encoding a 54.7 kDa protein was cloned and expressed in Escherichia coli,
      and purified recombinant TsAP protein was used to immunize BALB/c mice. The
      antibodies obtained were used to determine where TsAP was localized in the
      parasite. Transcription and expression of TsAP in different developmental stages
      of T. spiralis were observed by RT-PCR and Immunofluorescence test (IFT). The
      immune protection of recombinant TsAP protein against T. spiralis infection in
      BALB/c mice was evaluated. RESULTS: Anti-TsAP antibodies recognized the native
      protein migrating at 54.7 kDa by Western blotting of the crude antigens from
      muscle larvae. Transcription and expression of TsAP gene was observed in
      different developmental stages (adult worms, newborn larvae, pre-encapsulated
      larvae and muscle larvae). TsAP appears to be a cytoplasmic protein located
      primarily at the cuticle and internal organs of this parasite. After a challenge
      infection with T. spiralis infective larvae, mice immunized with the recombinant
      TsAP protein displayed a 38.1% reduction in adult worm burden and 59.1% reduction
      in muscle larval burden. CONCLUSIONS: In this study, T. spiralis aminopeptidase
      (TsAP) was first characterized and will help reveal its potential biological
      functions. TsAP is a novel potential vaccine candidate antigen that merits
      further investigation.

PMID- 23972036
TI  - Heart failure with normal ejection fraction: current diagnostic and management
      strategies.
AB  - Heart failure with normal ejection fraction (HFNEF), previously known as
      diastolic heart failure (HF), is defined as a syndrome of HF with normal or near
      normal ejection fraction (>= 50%) and evidence of abnormal left ventricular (LV)
      diastolic function. It represents about 50% of patients diagnosed with HF. HFNEF
      is not a benign disease as it carries a morbidity and mortality risk as high as
      that associated with HF and reduced ejection fraction (HFREF). HFNEF shares some
      risk factors, hemodynamic consequences and clinical presentations with HFREF,
      though they differ in the pathophysiology and cardiac morphology. Therapies such
      as beta-blockers (BBs) and angiotensin-receptor blockers (ARBs), which are
      beneficial in HFREF have not shown a survival benefit in HFNEF. Therapies focus
      on control of hypertension, control of heart rate, revascularization in case of
      ischemia for long term management and use of diuretics in acute decompensated
      HFNEF. Exercise therapy improves performance in HFNEF.

PMID- 23972035
TI  - Race and insurance disparities in discharge to rehabilitation for patients with
      traumatic brain injury.
AB  - Post-acute inpatient rehabilitation services are associated with improved
      functional outcomes among persons with traumatic brain injury (TBI). We sought to
      investigate racial and insurance-based disparities in access to rehabilitation.
      Data from the Nationwide Inpatient Sample from 2005-2010 were analyzed using
      standard descriptive methods and multivariable logistic regression to assess race
      and insurance-based differences in access to inpatient rehabilitation after TBI,
      controlling for patient- and hospital-level variables. Patients with moderate to
      severe TBI aged 18-64 years with complete data on race and insurance status
      discharged alive from inpatient care were eligible for study. Among 307,675 TBI
      survivors meeting study criteria and potentially eligible for discharge to
      rehabilitation, 66% were white, 12% black, 15% Hispanic, 2% Asian, and 5% other
      ethnic minorities. Most whites (70%), Asians (70%), blacks (59%), and many
      Hispanics (49%) had insurance. Compared with insured whites, insured blacks had
      reduced odds of discharge to rehabilitation (odds ratio [OR] 0.84; 95% confidence
      interval [CI] 0.75-0.95). Also, insured Hispanics (OR 0.52; 95% CI 0.44-0.60) and
      insured Asians (OR 0.54; 95% CI 0.39-0.73) were less likely to be discharged to
      rehabilitation than insured whites. Compared with insured whites, uninsured
      whites (OR 0.57; 95% CI 0.51-0.63), uninsured blacks (OR 0.33; 95% CI 0.26-0.42),
      uninsured Hispanics (OR 0.27; 95% CI 0.22-0.33), and uninsured Asians (OR 0.40;
      95% CI 0.22-0.73) were less likely to be discharged to rehabilitation. Race and
      insurance are strong predictors of discharge to rehabilitation among adult TBI
      survivors in the United States. Efforts are needed to understand and eliminate
      disparities in access to rehabilitation after TBI.

PMID- 23972037
TI  - Genetic variation in brown trout Salmo trutta across the Danube, Rhine, and Elbe
      headwaters: a failure of the phylogeographic paradigm?
AB  - BACKGROUND: Brown trout Salmo trutta have been described in terms of five major
      mtDNA lineages, four of which correspond to major ocean basins, and one,
      according to some authors, to a distinct taxon, marbled trout Salmo marmoratus.
      The Atlantic and Danubian lineages of brown trout meet in a poorly documented
      contact zone in Central Europe. The natural versus human mediated origin of the
      Atlantic lineage in the upper Danube is a question of both theoretical and
      practical importance with respect to conservation management. We provide a
      comprehensive population genetic analysis of brown trout in the region with the
      aim of evaluating the geographic distribution and genetic integrity of these two
      lineages in and around their contact zone. RESULTS: Genetic screening of 114
      populations of brown trout across the Danube/Rhine/Elbe catchments revealed a
      counter-intuitive phylogeographic structure with near fixation of the Atlantic
      lineage in the sampled portions of the Bavarian Danube. Along the Austrian
      Danube, phylogeographic informative markers revealed increasing percentages of
      Danube-specific alleles with downstream distance. Pure Danube lineage populations
      were restricted to peri-alpine isolates within previously glaciated regions. Both
      empirical data and simulated hybrid comparisons support that trout in non
      glaciated regions north and northeast of the Alps have an admixed origin largely
      based on natural colonization. In contrast, the presence of Atlantic basin
      alleles south and southeast of the Alps stems from hatchery introductions and
      subsequent introgression. Despite extensive stocking of the Atlantic lineage,
      little evidence of first generation stocked fish or F1 hybrids were found
      implying that admixture has been established over time. CONCLUSIONS: A purely
      phylogeographic paradigm fails to describe the distribution of genetic lineages
      of Salmo in Central Europe. The distribution pattern of the Atlantic and Danube
      lineages is extremely difficult to explain without invoking very strong
      biological mechanisms.The peri-alpine distribution of relict populations of pure
      Danubian lineage brown trout implies that they colonized headwater river courses
      post-glacially ahead of the expansion of the Atlantic lineage. The recognition of
      natural as opposed to anthropogenic introgression of the Atlantic lineage into
      Danubian gene pools is of fundamental importance to management strategies.

PMID- 23972038
TI  - Control of plasmonic and interband transitions in colloidal indium nitride
      nanocrystals.
AB  - We have developed a colloidal synthesis of 4-10 nm diameter indium nitride (InN)
      nanocrystals that exhibit both a visible absorption onset (~1.8 eV) and a strong
      localized surface plasmon resonance absorption in the mid-infrared (~3000 nm).
      Chemical oxidation and reduction reversibly modulate both the position and
      intensity of this plasmon feature as well as the band-to-band absorption onset.
      Chemical oxidation of InN nanocrystals with NOBF4 is found to red-shift the
      absorption onset to ~1.3 eV and reduce the plasmon absorption energy (to 3550 nm)
      and intensity (by an order of magnitude at 2600 nm). Reduction of these oxidized
      species with Bu4NBH4 fully recovers the original optical properties. Calculations
      suggest that the carrier density in these InN nanocrystals decreases upon
      oxidation from 2.89 * 10(20) cm(-3) to 2.51 * 10(20) cm(-3), consistent with the
      removal of ~4 electrons per nanocrystal. This study provides a unique example of
      the ability to tune the optical properties of colloidal nanomaterials, and in
      particular the LSPR absorption, with reversible redox reactions that do not
      affect the semiconductor chemical composition or phase. 

PMID- 23972040
TI  - New briarane-type diterpenoids from gorgonian Ellisella dollfusi from the South
      China Sea.
AB  - Two new briarane-type diterpenoids, dollfusilin A (1) and dollfusilin B (2),
      along with five known briarane-type diterpenoids (3-7), were isolated from the
      gorgonian Ellisella dollfusi collected from the South China Sea. The structures
      of the two new compounds (1 and 2) were elucidated through a comprehensive
      analysis of spectroscopic data, especially 2D NMR. The bioactivities of the
      isolated compounds were evaluated using the zebrafish toxicity model. 

PMID- 23972039
TI  - Effect of tenofovir with and without interferon on hepatitis D virus replication
      in HIV-hepatitis B virus-hepatitis D virus-infected patients.
AB  - The effect of tenofovir (TDF) alone or in combination with interferon on
      hepatitis D virus (HDV) replication is poorly characterized in patients infected
      with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and HDV. We
      analyzed triinfected patients undergoing treatment with either TDF alone (n=13)
      or including interferon (IFN) at some point during TDF therapy (TDF+IFN, n=4).
      Linear mixed-effect models were used to estimate the mean change from baseline of
      HDV-RNA and hepatitis surface antigen (HBsAg) levels during treatment. Patients
      were followed for a median 31.6 (25-75%-tile: 15.0-47.4) months. In the TDF+IFN
      group, three initiated IFN-based therapy after a median of 21.7 months
      (range=10.5-24.9) of lamivudine (LAM)+TDF, while the remaining patient had 46.8
      months of prior LAM exposure. Significant decreases in HDV-RNA were observed in
      both groups [TDF alone: -0.380 log10 copies/ml per year (95% CI: -0.557, -0.202)
      vs. TDF+IFN: -1.325 log10 copies/ml per year (95% CI: -1.931, -0.720)], while the
      HDV-RNA decline overall was significantly faster in patients with TDF+IFN
      (p=0.002). Accordingly, two patients achieved HDV-RNA below the limit of
      quantification (LOQ: <1,000 copies/ml) and one near LOQ (1450 copies/ml), all
      concomitantly treated with interferon. There were no significant changes in HBsAg
      levels for either group [TDF alone: -0.008 log10 IU/ml per month (95% CI: -0.019,
      0.004), TDF+IFN:-0.011 log10 IU/ml per month (95% CI: -0.037, 0.015)] and no
      significant difference in slope between treatment groups (p=0.8). Interferon
      therapy might be more effective after extended previous anti-HBV antiviral
      exposure among triinfected patients; however, the long-term implications of these
      findings remain unknown.

PMID- 23972042
TI  - Language and reading in the right hemisphere: highways or byways of the brain?
AB  - The literature pertaining to the representation of language in the right
      hemisphere of hemispherectomy and callosotomy patients is reviewed to ascertain
      whether it provides an empirical basis for the assertions that (1) the right
      hemisphere participates in the recovery of language in aphasia, (2) the right
      hemisphere mediates the reading errors of deep dyslexic and pure alexic patients,
      and (3) the right hemisphere plays a fixed role in normal reading processes. At
      present, there appears to be some support for the first assertion, limited
      support for the second (if individual variation in representation can be
      accepted), and disconfirming evidence for the third in the data from these
      populations. 

PMID- 23972041
TI  - Screening for type 2 diabetes: a short report for the National Screening
      Committee.
AB  - BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) has been
      increasing, owing to increases in overweight and obesity, decreasing physical
      activity and the changing demographic structure of the population. People can
      develop T2DM without symptoms and up to 20% may be undiagnosed. They may have
      diabetic complications, such as retinopathy, by the time they are diagnosed, or
      may suffer a heart attack, without warning. Undiagnosed diabetes can be detected
      by raised blood glucose levels. AIM: The aim of this review was to provide an
      update for the UK National Screening Committee (NSC) on screening for T2DM.
      METHODS: As this review was undertaken to update a previous Health Technology
      Assessment review published in 2007, and a more recent Scottish Public Health
      Network review, searches for evidence were restricted from 2009 to end of January
      2012, with selected later studies added. The databases searched were MEDLINE,
      EMBASE, MEDLINE-in-Process & Other Non-Indexed Citations, Science Citation Index
      and Conference Proceedings Citation Index. The case for screening was considered
      against the criteria used by the NSC to assess proposed population screening
      programmes. RESULTS: Population screening for T2DM does not meet all of the NSC
      criteria. Criterion 12, on optimisation of existing management, has not been met.
      A report by the National Audit Office (NAO) gives details of shortcomings.
      Criterion 13 requires evidence from high-quality randomised controlled trials
      that screening is beneficial. This has not been met. The Ely trial of screening
      showed no benefit. The ADDITION trial was not a trial of screening, but showed no
      benefit in cardiovascular outcomes from intensive management in people with
      screen-detected T2DM. Criterion 18 on staffing and facilities does not appear to
      have been met, according to the NAO report. Criterion 19 requires that all other
      options, including prevention, should have been considered. A large proportion of
      cases of T2DM could be prevented if people avoided becoming overweight or obese.
      The first stage of selection would use risk factors, using data held on general
      practitioner computer systems, using the QDiabetes Risk Score, or by sending out
      questionnaires, using the Finnish Diabetes Risk Score (FINDRISC). Those at high
      risk would have a measure of blood glucose. There is no perfect screening test.
      Glycated haemoglobin (HbA1c) testing has advantages in not requiring a fasting
      sample, and because it is a predictor of vascular disease across a wider range
      than just the diabetic one. However, it lacks sensitivity and would miss some
      people with diabetes. Absolute values of HbA1c may be more useful as part of
      overall risk assessment than a dichotomous 'diabetes or not diabetes' diagnosis.
      The oral glucose tolerance test is more sensitive, but inconvenient, more costly,
      has imperfect reproducibility and is less popular, meaning that uptake would be
      lower. CONCLUSIONS: When considered against the NSC criteria, the case for
      screening is less strong than it was in the 2007 review. The main reason is the
      absence of cardiovascular benefit in the two trials published since the previous
      review. There is a case for selective screening as part of overall vascular risk
      assessment. Population screening for T2DM does not meet all of the NSC criteria.
      FUNDING: The National Institute for Health Research Health Technology Assessment
      programme.

PMID- 23972043
TI  - The pyramidal cell and its local-circuit interneurons: a hypothetical unit of the
      Mammalian cerebral cortex.
AB  - A pyramidal cell with five of its local-circuit interneurons (Cajal-Retzius,
      Martinotti, Cajal double-bouquet, basket, and chandelier cells), constitutes a
      distinct structural/functional assemblage of the mammalian neocortex. This
      pyramidal/local-circuit neuronal assemblage is proposed herein as a basic
      neocortical unit. This unit is shared by all mammals, embodies both specific
      structural as well as functional elements, and constitutes an essential
      developmental building block of the neocortex. In the model, the pyramidal cell
      represents a distinct, stable, projective, excitatory neuron that has remained
      essentially unchanged in the course of mammalian phylogeny. On the other hand,
      its local-circuit interneurons are more likely to be inhibitory and less stable,
      designed perhaps to adapt, and modify in response to environmental needs. The
      proposed model infers that the number of pyramidal cells contacted by each local
      circuit interneuron as well as the number of synaptic contacts established with
      each one are elements acquired post-natally in response to individual needs.
      Thereby, the overall three-dimensional distribution and extent of these
      pyramidal/local-circuit neuronal assemblages should be species-specific, variable
      among individual of the same species, and able to adapt in response to
      environmental needs. The model introduces a different approach, perhaps a new
      vantage point, for the study of the basic structural organization of the
      mammalian cerebral cortex. Relationships of the proposed model to cortical
      function in general and to learning behavior in particular are discussed. 

PMID- 23972044
TI  - Music perception and cognition following bilateral lesions of auditory cortex.
AB  - We present experimental and anatomical data from a case study of impaired
      auditory perception following bilateral hemispheric strokes. To consider the
      cortical representation of sensory, perceptual, and cognitive functions mediating
      tonal information processing in music, pure tone sensation thresholds, spectral
      intonation judgments, and the associative priming of spectral intonation
      judgments by harmonic context were examined, and lesion localization was analyzed
      quantitatively using straight-line two-dimensional maps of the cortical surface
      reconstructed from magnetic resonance images. Despite normal pure tone sensation
      thresholds at 250-8000 Hz, the perception of tonal spectra was severely impaired,
      such that harmonic structures (major triads) were almost uniformly judged to
      sound dissonant; yet, the associative priming of spectral intonation judgments by
      harmonic context was preserved, indicating that cognitive representations of
      tonal hierarchies in music remained intact and accessible. Brainprints
      demonstrated complete bilateral lesions of the transverse gyri of Heschl and
      partial lesions of the right and left superior temporal gyri involving 98 and 20%
      of their surface areas, respectively. In the right hemisphere, there was partial
      sparing of the planum temporale, temporoparietal junction, and inferior parietal
      cortex. In the left hemisphere, all of the superior temporal region anterior to
      the transverse gyrus and parts of the planum temporale, temporoparietal junction,
      inferior parietal cortex, and insula were spared. These observations suggest that
      (1) sensory, perceptual, and cognitive functions mediating tonal information
      processing in music are neurologically dissociable; (2) complete bilateral
      lesions of primary auditory cortex combined with partial bilateral lesions of
      auditory association cortex chronically impair tonal consonance perception; (3)
      cognitive functions that hierarchically structure pitch information and generate
      harmonic expectancies during music perception do not rely on the integrity of
      primary auditory cortex; and (4) musical priming may be mediated by broadly tuned
      subcomponents of the thala-mocortical auditory system. 

PMID- 23972045
TI  - Simulating visual attention.
AB  - Selective visual attention serializes the processing of stimulus data to make
      efficient use of limited processing resources in the human visual system. This
      paper describes a connectionist network that exhibits a variety of attentional
      phenomena reported by Treisman, Wolford, Duncan, and others. As demonstrated in
      several simulations, a hierarchical, multiscale network that uses feature arrays
      with strong lateral inhibitory connections provides responses in agreement with a
      number of prominent behaviors associated with visual attention. The overall
      network design is consistent with a range of data reported in the psychological
      literature, and with neurophysiol-ogical characteristics of primate vision. 

PMID- 23972046
TI  - Orienting Attention across the Vertical Meridian: Evidence from Callosotomy
      Patients.
AB  - This study investigates whether interhemispheric interactions mediated by the
      corpus callosum play a role in orienting attention across the vertical meridian.
      Patients with complete or partial section of the corpus callosum participated in
      a spatial precueing task under conditions that required covert shifts of
      attention within or between the visual fields. Patients with complete callosal
      section demonstrated normal costs on invalid trials when the cue and target
      appeared in the same visual field. However, these patients were impaired on
      invalid trials in which attention had to be redirected across the vertical
      meridian. The between-within difference emerged only for patients with complete
      callosal section; it was not evident for a patient with section restricted to the
      anterior two-thirds of the callosum. Control experiments demonstrated that the
      deficit (1) is specific to shifts across the vertical meridian, (2) is not due to
      shifting between left and right hemispace, and (3) is related to the voluntary
      allocation of attention in response to the cue. These results suggest that
      interhemispheric communication, which is normally mediated by the posterior
      region of the corpus callosum, contributes to the efficient movement of attention
      between visual fields. 

PMID- 23972047
TI  - Hemispheric mechanisms controlling voluntary and spontaneous facial expressions.
AB  - The capacity of each disconnected cerebral hemisphere to control a variety of
      facial postures was examined in three split-brain patients. The dynamics of
      facial posturing were analyzed in 30-msec optical disc frames that were generated
      off videotape recordings of each patient's response to lateralized stimuli. The
      results revealed that commands presented to the left hemisphere effecting
      postures of the lower facial muscles showed a marked asymmetry, with the right
      side of the face sometimes responding up to 180 msec before the left side of the
      face. Commands presented to the right hemisphere elicited a response only if the
      posture involved moving the upper facial muscles. Spontaneous postures filmed
      during free conversation were symmetrical. The results suggest that while either
      hemisphere can generate spontaneous facial expressions only the left hemisphere
      is efficient at generating voluntaly expressions. This contrasts sharply with the
      fact that both hemispheres can carry out a wide variety of other voluntary
      movements with the hand and foot. 

PMID- 23972048
TI  - Amnesia due to Lesions Confined to the Hippocampus: A Clinical-Pathologic Study.
AB  - Reported here is the case of a 65-year-old man who suffered a burst of severe,
      repetitive generalized seizures (status epilepticus). On recovery of
      consciousness he was left with a profound impairment of memory, which remained
      unchanged for the subsequent 30 months of his life. During this period the
      cognitive defect was fully documented. Careful neuropathologic examination
      disclosed the presence of remarkably discrete lesions, confined to the
      hippocampus on each side. Because of the rarity of well-documented instances of
      this type and their importance in the study of memory function, we are reporting
      our case in some detail. 

PMID- 23972049
TI  - Late positive event-related potentials after commissural section in humans.
AB  - The lateral distribution of the P300 component of the event-related brain
      potential (ERP) was studied in five epileptic patients whose corpus callosum had
      been surgically sectioned and in seven neurologically intact controls. The P300
      was elicited in an auditory "oddball" task using high- and low-pitched tones and
      in a visual oddball task in which target words were presented either to the left
      or right visual fields, or to both fields simultaneously. Commissurotomy altered
      the normal pattern of bilaterally symmetrical P300 waves over the left and right
      hemispheres, but in a different manner for auditory and visual stimuli. The
      auditory P3 to binaural tones was larger in amplitude over the right than the
      left hemisphere for the patients. In the visual task, the laterality of the P300
      varied with the visual field of the target presentation. Left field targets
      elicited much larger P300 amplitudes over the right than the left hemisphere, as
      did bilateral targets. In contrast, right field targets triggered P300 waves of
      about the same amplitude over the two hemispheres. The overall amplitude of the
      P300 to simultaneous bilateral targets was less than the sum of the individual
      P300 amplitudes produced in response to the unilateral right and left field
      targets. These shifts in P300 laterality argue against the view that the P300 is
      an index of diffuse arousal or activation that is triggered in both hemispheres
      simultaneously irrespective of which hemisphere processes the target information.
      The results further demonstrate that the P300 does not depend for its production
      on interhemispheric comparisons of information mediated by the corpus callosum,
      as suggested recently by Knight et al. (1989). 

PMID- 23972050
TI  - Global versus local processing in the absence of low spatial frequencies.
AB  - When observers are presented with hierarchical visual stimuli that contain
      incongruous coarse ("global") and fine ("local") pattern attributes, the global
      structure interferes with local pattern processing more than local structure
      interferes with global pattern processing. This effect is referred to as "global
      precedence." The present experiments tested the hypothesis that global precedence
      depends on the presence of low spatial frequencies using stimuli constructed from
      "contrast balanced dots." Stimuli composed of contrast balanced dots are largely
      devoid of low-frequency content. Choice reaction time to identify either the
      local or global pattern information was the dependent measure. Global precedence
      was found only for control stimuli that contained low spatial frequencies. In the
      absence of low-frequency information, local precedence was obtained. These
      findings suggest that global precedence is heavily dependent on the low spatial
      frequency content of the patterns. 

PMID- 23972051
TI  - From reading to neurons.

PMID- 23972052
TI  - Using peer-assisted learning to teach basic surgical skills: medical students'
      experiences.
AB  - Standard medical curricula in the United Kingdom (UK) typically provide basic
      surgical-skills teaching before medical students are introduced into the clinical
      environment. However, these sessions are often led by clinical teaching fellows
      and/or consultants. Depending on the roles undertaken (e.g., session organizers,
      peer tutors), a peer-assisted learning (PAL) approach may afford many benefits to
      teaching surgical skills. At the University of Keele's School of Medicine,
      informal PAL is used by the Surgical Society to teach basic surgical skills to
      pre-clinical students. As medical students who assumed different roles within
      this peer-assisted model, we present our experiences and discuss the possible
      implications of incorporating such sessions into UK medical curricula. Our
      anecdotal evidence suggests that a combination of PAL sessions--used as an
      adjunct to faculty-led sessions--may provide optimal learning opportunities in
      delivering a basic surgical skills session for pre-clinical students.

PMID- 23972053
TI  - Automaticity and conscious control in single and choice response time versions of
      the Perruchet effect.
AB  - The Perruchet effect refers to a dissociation between conscious expectation of an
      event and the strength or speed of the response elicited by that event, which is
      revealed through sequential analyses of consecutive trials. For instance in a
      cued go/no-go task, over a run of consecutive go responses, participants perform
      the go task with increasing speed but display decreasing expectancy of the go
      response when asked to rate the likelihood of its occurrence, in line with a
      gambler's fallacy. The effect has conventionally been shown in procedures that
      measure expectancy and responding in separate blocks of trials (separate
      measurement) or measure both on the same trial (concurrent measurement). Here we
      directly compared the trends produced in separate and concurrent measurement
      procedures, using single response and two-choice response procedures. While the
      single response showed the same trends regardless of measurement style, the
      Perruchet dissociation disappeared when concurrent measurement was used with the
      choice response task. Furthermore, in the concurrent measurement versions of both
      tasks, those participants who produced a consistent gambler's fallacy did not
      show the standard effects of positive recency that underpin the Perruchet effect
      in response time. The results suggest that explicit expectation of events and
      facilitation based on recent trial history have dissociable but competing effects
      on response performance.

PMID- 23972054
TI  - Spatial compatibility effects with unimanual and bimanual wheel-rotation
      responses: an homage to guiard (1983).
AB  - Y. Guiard (1983) reported a prescient study of compatibility effects in response
      times for clockwise/counterclockwise wheel rotations to stimuli in left/right
      locations. Left-right coding of responses predominated in his study, but some
      results suggested that unimanual versus bimanual operation was also a factor. The
      authors report 3 experiments directly examining whether there is a difference in
      spatial compatibility effects obtained with wheel-rotation responses executed
      bimanually or unimanually (with left or right hand). Adopting a right-to
      clockwise or left-to-counterclockwise mapping was advantageous for top, side, and
      bottom hand placements. This benefit interacted neither with unimanual or
      bimanual responding nor with the response hand. The results confirm that the
      critical relation is between the wheel and stimulus position, and is not effector
      dependent. This finding is in agreement with results from studies using discrete
      keypress responses, emphasizing that spatial coding of stimuli, actions, and
      their goals is of central importance in response-selection decisions.

PMID- 23972055
TI  - Implementing a provider-initiated testing and counselling (PITC) intervention in
      Cape town, South Africa: a process evaluation using the normalisation process
      model.
AB  - BACKGROUND: Provider-initiated HIV testing and counselling (PITC) increases HIV
      testing rates in most settings, but its effect on testing rates varies
      considerably. This paper reports the findings of a process evaluation of a
      controlled trial of PITC for people with sexually transmitted infections (STI)
      attending publicly funded clinics in a low-resource setting in South Africa,
      where the trial results were lower than anticipated compared to the standard
      Voluntary Counselling and Testing (VCT) approach. METHOD: This longitudinal study
      used a variety of qualitative methods, including participant observation of
      project implementation processes, staff focus groups, patient interviews, and
      observation of clinical practice. Data were content analysed by identifying the
      main influences shaping the implementation process. The Normalisation Process
      Model (NPM) was used as a theoretical framework to analyse implementation
      processes and explain the trial outcomes. RESULTS: The new PITC intervention
      became embedded in practice (normalised) during a two-year period (2006 to 2007).
      Factors that promoted the normalising include strong senior leadership,
      implementation support, appropriate accountability mechanisms, an intervention
      design that was responsive to service needs and congruent with professional
      practice, positive staff and patient perceptions, and a responsive organisational
      context. Nevertheless, nurses struggled to deploy the intervention efficiently,
      mainly because of poor sequencing and integration of HIV and STI tasks, a focus
      on HIV education, tension with a patient-centred communication style, and
      inadequate training on dealing with the operational challenges. This resulted in
      longer consultation times, which may account for the low test coverage outcome.
      CONCLUSION: Leadership and implementation support, congruent intervention design,
      and a responsive organisational context strengthened implementation. Poor
      compatibility with nurse skills on the level of the clinical consultation may
      have contributed to limiting the size of the trial outcomes. A close fit between
      the PITC intervention design and clinical practices, as well as appropriate
      training, are needed to ensure sustainability of the programme. The use of a
      theory-driven analysis promotes transferability of the results, and the findings
      are therefore relevant to the implementation of HIV testing and to the design and
      evaluation of complex interventions in other settings. TRIAL REGISTRATION:
      Current controlled trials ISRCTN93692532.

PMID- 23972056
TI  - The vicious cycle of dialysis-induced cardiac injury--are dynamic changes in
      diastolic function involved?

PMID- 23972057
TI  - Integrated pharmacy services: a necessary component for care of patients treated
      by long-term dialysis.

PMID- 23972058
TI  - Living kidney donation: biochemical changes and patient outcomes.

PMID- 23972059
TI  - In reply to 'Primary objective of study of sitagliptin in patients with ESRD on
      dialysis'.

PMID- 23972060
TI  - Primary objective of study of sitagliptin in patients with ESRD on dialysis.

PMID- 23972061
TI  - Thrombolytic protocol potentially reduces catheter-related complications in
      hemodialysis patients.

PMID- 23972062
TI  - In reply to 'Thrombolytic protocol potentially reduces catheter-related
      complications in hemodialysis patients'.

PMID- 23972063
TI  - Phosphate balance with continuous renal replacement therapy: a simple solution.

PMID- 23972064
TI  - Progression of vascular calcification in kidney transplantation: the need to
      assess the calcium burden and to understand why some patients have a calcium
      score of 0.

PMID- 23972065
TI  - Quiz page September 2013: a crystal clear diagnosis.

PMID- 23972066
TI  - Role of the vitamin K epoxide reductase complex subunit 1 (VKORC1) -1639G>A gene
      polymorphism in patients with retinal vein occlusion.
AB  - PURPOSE OF THE STUDY: Retinal vein occlusion (RVO) is a major vision-threatening
      disease. Vitamin K epoxide reductase recycles reduced vitamin K, which is
      essential for the gamma carboxylation of clotting factors II, VII, IX, X and
      proteins C and S. Recently, the vitamin K epoxide reductase complex subunit 1
      (VKORC1) -1639G>A (rs9923231) polymorphism has been reported as a novel risk
      factor for RVO in a Turkish population. The present study was set to confirm or
      to refute this association in a larger cohort of patients with RVO. MATERIALS AND
      METHODS: The present case-control study comprised 285 patients with central RVO,
      401 patients with branch RVO and 333 control subjects. Genotypes of the VKORC1 
      1639G>A polymorphism were determined by 5' exonuclease assay (TaqMan). RESULTS:
      No significant differences in either genotype distributions or allele frequencies
      of the vitamin K epoxide reductase complex subunit 1 -1639G>A polymorphism were
      found between patients and control subjects (p > 0.05). In a logistic regression
      analysis neither branch nor central RVO was predicted by the vitamin K epoxide
      reductase complex subunit 1 -1639G>A genotypes, but by arterial hypertension,
      ever-smoking status and in case of central RVO additionally by diabetes mellitus.
      CONCLUSIONS: Our data suggest that the vitamin K epoxide reductase complex
      subunit 1 -1639G>A gene polymorphism is unlikely a major risk factor for patients
      with either central or branch RVO.

PMID- 23972068
TI  - Paramagnetic ionic liquids for measurements of density using magnetic levitation.
AB  - Paramagnetic ionic liquids (PILs) provide new capabilities to measurements of
      density using magnetic levitation (MagLev). In a typical measurement, a
      diamagnetic object of unknown density is placed in a container containing a PIL.
      The container is placed between two magnets (typically NdFeB, oriented with like
      poles facing). The density of the diamagnetic object can be determined by
      measuring its position in the magnetic field along the vertical axis (levitation
      height, h), either as an absolute value or relative to internal standards of
      known density. For density measurements by MagLev, PILs have three advantages
      over solutions of paramagnetic salts in aqueous or organic solutions: (i)
      negligible vapor pressures; (ii) low melting points; (iii) high thermal
      stabilities. In addition, the densities, magnetic susceptibilities, glass
      transition temperatures, thermal decomposition temperatures, viscosities, and
      hydrophobicities of PILs can be tuned over broad ranges by choosing the cation
      anion pair. The low melting points and high thermal stabilities of PILs provide
      large liquidus windows for density measurements. This paper demonstrates
      applications and advantages of PILs in density-based analyses using MagLev. 

PMID- 23972067
TI  - Discovery of a substrate selectivity motif in amino acid decarboxylases unveils a
      taurine biosynthesis pathway in prokaryotes.
AB  - Taurine, the most abundant free amino acid in mammals, with many critical roles
      such as neuronal development, had so far only been reported to be synthetized in
      eukaryotes. Taurine is the major product of cysteine metabolism in mammals, and
      its biosynthetic pathway consists of cysteine dioxygenase and cysteine sulfinic
      acid decarboxylase (hCSAD). Sequence, structural, and mutational analyses of the
      structurally and sequentially related hCSAD and human glutamic acid decarboxylase
      (hGAD) enzymes revealed a three residue substrate recognition motif
      (X1aa19X2aaX3), within the active site that is responsible for coordinating their
      respective preferred amino acid substrates. Introduction of the cysteine sulfinic
      acid (CSA) motif into hGAD (hGAD-S192F/N212S/F214Y) resulted in an enzyme with a
      >700 fold switch in selectivity toward the decarboxylation of CSA over its
      preferred substrate, l-glutamic acid. Surprisingly, we found this CSA recognition
      motif in the genome sequences of several marine bacteria, prompting us to
      evaluate the catalytic properties of bacterial amino acid decarboxylases that
      were predicted by sequence motif to decarboxylate CSA but had been annotated as
      GAD enzymes. We show that CSAD from Synechococcus sp. PCC 7335 specifically
      decarboxylated CSA and that the bacteria accumulated intracellular taurine. The
      fact that CSAD homologues exist in certain bacteria and are frequently found in
      operons containing the recently discovered bacterial cysteine dioxygenases that
      oxidize l-cysteine to CSA supports the idea that a bona fide bacterial taurine
      biosynthetic pathway exists in prokaryotes. 

PMID- 23972069
TI  - Endoglucanase peripheral loops facilitate complexation of glucan chains on
      cellulose via adaptive coupling to the emergent substrate structures.
AB  - We examine how the catalytic domain of a glycoside hydrolase family 7
      endoglucanase catalytic domain (Cel7B CD) facilitates complexation of cellulose
      chains from a crystal surface. With direct relevance to the science of biofuel
      production, this problem also represents a model system of biopolymer processing
      by proteins in Nature. Interactions of Cel7B CD with a cellulose microfibril
      along different paths of complexation are characterized by mapping the atomistic
      fluctuations recorded in free-energy simulations onto the parameters of a coarse
      grain model. The resulting patterns of protein-biopolymer couplings also uncover
      the sequence signatures of the enzyme in peeling off glucan chains from the
      microfibril substrate. We show that the semiopen active site of Cel7B CD exhibits
      similar barriers and free energies of complexation over two distinct routes;
      namely, scooping of a chain into the active-site cleft and threading from the
      chain end into the channel. On the other hand, the complexation energetics
      strongly depends on the surface packing of the targeted chain and the resulting
      interaction sites with the enzyme. A revealed principle is that Cel7B CD
      facilitates cellulose deconstruction via adaptive coupling to the emergent
      substrate. The flexible, peripheral segments of the protein outside of the active
      site cleft are able to accommodate the varying features of cellulose along the
      simulated paths of complexation. The general strategy of linking physics-based
      molecular interactions to protein sequence could also be helpful in elucidating
      how other protein machines process biopolymers. 

PMID- 23972070
TI  - Persistent extreme regressive behavior in severe traumatic brain injury patients:
      a rare neurological phenomenon.
AB  - Regressive behavior is a known sequela after severe traumatic brain injury (TBI).
      However, prolonged "infantile-like" behavior has received little attention in the
      literature, suggesting that this is a rare phenomenon. It is typically
      characterized by long-lasting childish, extremely dependent, and sometimes
      aggressive behavior, which is distinguished from the expected recovery process.
      The relevant theoretical framework lies in the field of disorders called
      "Neuropathologies of the self" (NPS). We report three cases of young adults who,
      following a severe TBI, developed continual regressive behavior. The Disability
      Rating Scale (DRS) was used to assess possible change in their condition. First,
      while admitted, which was performed in retrospect, and again 6 years later at the
      time stated. Inter-rater reliability for the scale items showed adequate
      correlation. Results showed no significant difference in patients' scores,
      indicating persistent functional difficulties. We conclude that this "regressive
      syndrome" presents an unusual form of behavior that is stable over time. It seems
      to be in line with other NPS disorders, and may stem from an interaction of
      organic factors and primary mental complexity. Nevertheless, further research is
      required to examine the factors affecting the emergence and recovery from this
      phenomenon. 

PMID- 23972071
TI  - A review of devices used in the monitoring of microvascular free tissue
      transfers.
AB  - The use of microvascular anastomoses to allow transfer of viable tissue is a
      fundamental technique of reconstructive surgery, and is used to treat a broad
      spectrum of clinical problems. The primary threat to this type of reconstructive
      surgery is anastomotic vascular thrombosis, which can lead to complete loss of
      tissue with potentially devastating consequences. Monitoring of tissue perfusion
      postoperatively is critical, since early recognition of vascular compromise and
      prompt surgical intervention is correlated with the ability for tissue salvage.
      Traditionally, physical examination was the primary means of monitoring, but
      possesses several limitations. Medical devices introduced for the purposes of
      flap monitoring address many of these deficiencies, and have greatly enhanced
      this critical aspect of the reconstructive surgery process. 

PMID- 23972072
TI  - The use of reinforcement learning algorithms to meet the challenges of an
      artificial pancreas.
AB  - Blood glucose control, for example, in diabetes mellitus or severe illness,
      requires strict adherence to a protocol of food, insulin administration and
      exercise personalized to each patient. An artificial pancreas for automated
      treatment could boost quality of glucose control and patients' independence. The
      components required for an artificial pancreas are: i) continuous glucose
      monitoring (CGM), ii) smart controllers and iii) insulin pumps delivering the
      optimal amount of insulin. In recent years, medical devices for CGM and insulin
      administration have undergone rapid progression and are now commercially
      available. Yet, clinically available devices still require regular patients' or
      caregivers' attention as they operate in open-loop control with frequent user
      intervention. Dosage-calculating algorithms are currently being studied in
      intensive care patients [1] , for short overnight control to supplement
      conventional insulin delivery [2] , and for short periods where patients rest and
      follow a prescribed food regime [3] . Fully automated algorithms that can respond
      to the varying activity levels seen in outpatients, with unpredictable and
      unreported food intake, and which provide the necessary personalized control for
      individuals is currently beyond the state-of-the-art. Here, we review and discuss
      reinforcement learning algorithms, controlling insulin in a closed-loop to
      provide individual insulin dosing regimens that are reactive to the immediate
      needs of the patient. 

PMID- 23972073
TI  - Considerations on the development of a model of kidney bioengineering and
      regeneration in rats.
AB  - Evaluation of: Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC.
      Regeneration and experimental orthotopic transplantation of a bioengineered
      kidney. Nat. Med. 19(5), 646-51 (2013). Emergent technologies of regenerative
      medicine have shown immense potential to overcome the limitations of organ
      transplantation by supplying tissues and organs bioengineered ex vivo in the
      laboratory. So far, clinical translation has been possible for simple, hollow
      organs, whereas the bioengineering and regeneration of complex modular organs
      (namely, kidneys, hearts, livers, lungs and small bowel) remains far from our
      grasp. In the case of the kidney, the bioengineering and regeneration of renal
      organoids requires a supporting scaffold that approximates the biochemical,
      spatial and vascular relationships of the native kidney extracellular matrix. A
      recent report describes the use of rodent kidneys to generate whole organ, three
      dimensional scaffolds. These scaffolds were subsequently seeded with rat neonatal
      kidney cells to reconstitute the parenchymal cell compartment and with human
      umbilical venous endothelial cells to reconstitute the endothelium and allow
      implantation. Once assembled and allowed to mature in bioreactors, the so
      obtained constructs were able to exert some function peculiar to the kidney both
      in vitro and in vivo after implantation in rodents. In this invited commentary,
      we will address the most critical topics of organ regeneration starting from the
      above-mentioned experience with the kidney but eventually embracing the whole
      field of complex modular organs bioengineering. 

PMID- 23972075
TI  - Improved visualization of deep ocular structures in glaucoma using high
      penetration optical coherence tomography.
AB  - The introduction of optical coherence tomography (OCT) has revolutionized
      ophthalmology through the ability to non-invasively image the retina in vivo.
      Glaucoma is the leading cause of irreversible blindness worldwide. Despite major
      advances in imaging techniques, the pathogenesis of glaucoma remains poorly
      understood at present. The lamina cribrosa (LC) is the presumed site of axonal
      injury in glaucoma. Its thinning and deformation have been suggested to
      contribute to glaucoma development and progression by impeding axoplasmic flow
      within the optic nerve fibers, leading to apoptosis of retinal ganglion cells. To
      visualize the deep ocular structures such as the choroid and the LC, OCT imaging
      has been used, particularly the enhanced depth imaging (EDI)-OCT modality of
      spectral domain (SD)-OCT. However, the posterior laminar surface especially is
      not seen clearly using this method. A new generation of OCTs, swept-source (SS)
      OCT, is able to image the LC and the choroid in vivo. SS-OCT employs a longer
      wavelength compared with the conventional OCT, generally set at 1050 nm (instead
      of 840 nm). We review current knowledge of the LC, findings from trials that use
      SD-OCT and EDI-OCT, and our experience with a prototype SS-OCT to quantify
      choroid changes and visualize the LC in its entirety. 

PMID- 23972074
TI  - Linear and radial endobronchial ultrasound in diagnosis and staging of lung
      cancer.
AB  - Endobronchial ultrasound (EBUS) in recent years has become a routine diagnostic
      procedure in bronchology. Linear EBUS shows high diagnostic yield in evaluation
      of mediastinal lymph nodes. It is mainly used for nodal evaluation in lung
      cancer, but has also proven to be efficient in diagnostic evaluation of
      mediastinal masses. This technique has been shown to be complementary to
      mediastinoscopy. In combination with PET and rapid on site cytology (ROSE), the
      diagnostic yield of EBUS is significantly higher. Radial EBUS is used for
      diagnosis of peripheral lung lesions. This technique facilitates evaluation of
      bronchial wall in central lung cancer lesions, enabling differentiation between
      early and invasive lung cancer. The diagnostic yield of radial EBUS in the
      diagnostics of peripheral lung lesions is high, reducing the number of diagnostic
      thoracotomies. The application of miniature radial EBUS probes, together with
      guiding sheaths and other guiding accessories, allow the access to smaller and
      more peripheral lung lesions. In addition, EBUS bronchoscopy can be utilized for
      the placement of brachytherapy catheters, or evaluation of the distal bronchi in
      order to chose between different therapeutic bronchoscopic techniques for
      desobstruction. An experienced bronchoscopist, availability of ROSE and
      additional guiding devices might be necessary to accomplish the best possible
      results of EBUS bronchoscopy. 

PMID- 23972076
TI  - Pacemaker reuse: an initiative to help those in underserved nations in need of
      life-saving device therapy.

PMID- 23972077
TI  - Fractals in tissue engineering: toward biomimetic cell-culture matrices,
      microsystems and microstructured implants.
AB  - Tissue engineering is a rapidly evolving field in which the complexity of
      biomaterials and biostructures, with typically non-Euclidean or fractal-like
      geometries, has to be adequately taken into account for the promotion of enhanced
      and even personalized diagnostic and therapeutic solutions. This study covers the
      main applications of fractals in the field of tissue engineering, including their
      advantages for modeling biological processes and cell-culture procedures, but
      specially focusing on their benefits for describing the complex geometries and
      structures of biomaterials (both natural and synthetic), many of which have
      potential uses for the development of cell culture microsystems, scaffolds for
      tissue repair and implants for tissue repair in general. We also explore the main
      supporting design, simulation and manufacturing technologies, as well as the most
      remarkable difficulties and limitations linked to the generalized use of fractals
      in engineering design, and also detail some current solution proposals and future
      directions. 

PMID- 23972078
TI  - Thermoresponsive microgel films for harvesting cells and cell sheets.
AB  - This work reports the formation of thermoresponsive poly(N-isopropylacrylamide-co
      styrene) (PNIPAAmSt) microgel films and their use for cell growth and detachment
      via temperature stimuli. Thermoresponsive surface films can be conveniently
      produced by spin-coating or drop-coating of PNIPAAmSt microgel dispersions onto
      substrates such as glass coverslips, cell culture plates, and flasks, making this
      technique widely accessible. The thickness, stability, and reversibility of the
      PNIPAAmSt films coated on silicon wafers with respect to temperature switching
      were examined by spectroscopic ellipsometry (SE) and atomic force microscopy
      (AFM). The results unraveled the direct link between thermoreversibility and
      changes in film thickness and surface morphology, showing reversible hydration
      and dehydration. Under different coating conditions, well-packed microgel
      monolayers could be utilized for effective cell recovery and harvesting.
      Furthermore, cell adhesion and detachment processes were reversible and there was
      no sign of loss of cell viability during repeated surface attachment, growth, and
      detachment, showing a mild interaction between cells and thermoresponsive
      surface. More importantly, there was little deterioration of the packing of the
      thermoresponsive films or any major loss of microgel particles during reuse,
      indicating their robustness. These PNIPAAmSt microgel films thus open up a
      convenient interfacial platform for cell and cell sheet harvesting while avoiding
      the damage of enzymatic cleavage. 

PMID- 23972079
TI  - Safety of intracorporeal circular stapling esophagojejunostomy using trans-orally
      inserted anvil (OrVil) following laparoscopic total or proximal gastrectomy -
      comparison with extracorporeal anastomosis.
AB  - BACKGROUND: There have been several attempts to develop a unique and easier way
      to perform esophagojejunostomy during laparoscopy-assisted total gastrectomy or
      laparoscopy-assisted proximal gastrectomy. The OrVil system (Covidien, Mansfield,
      MA, USA) is one of those methods, but its technical and oncologic feasibility
      have not been proven and need to be observed. METHODS: Among 87 patients who
      underwent laparoscopy-assisted total gastrectomy (LATG; 79 cases) and laparoscopy
      assisted proximal gastrectomy with double tract anastomosis (LAPG_DT; 8 cases)
      from April 2004, 47 patients underwent the conventional extracorporeal method
      (Group I; 2004-2008) were compared with 40 patients treated with the
      intracorporeal OrVil system (Group II; 2009-2012). RESULTS: There was no
      significant difference in clinicopathologic characteristics between the two
      groups except tumor location; more cardia lesions were involved in group II (p =
      0.012). The mean time for esophagojejunostomy (E-J), defined as the time from
      anvil insertion to closure of the jejunal entry site has no significant
      difference (Group I vs II: 22.2 +/- 3.2 min vs 18.6 +/- 3.5 min, p = 0.623). In
      terms of anastomotic complication, there was no significant difference in E-J
      leakage and stricture. E-J leakage occurred in 2 out of 47 (4.3%) cases in group
      I and 2 out of 40 (5%) in group II (p = 0.628); half of them were treated
      conservatively in each group and the others underwent reoperation. E-J stricture
      occurred in 2 (4.3%) cases in group I and 1 (2.5%) in group II (p = 0.561), which
      required postoperative gastrofiberscopic balloon dilatation. CONCLUSIONS:
      Esophagojejunostomy using the OrVil system was a feasible and safe technique
      compared with the conventional extracorporeal method through mini-laparotomy in
      terms of anastomotic complications. Moreover, it can help to reduce surgeon's
      stress regarding esophagojejunostomy because it needs no purse-string procedure
      and serves a secure operation view laparoscopically.

PMID- 23972080
TI  - A new trans-neoclerodane diterpene from Stachys aegyptiaca.
AB  - Phytochemical investigation of the methylenechloride/methanol extract of the
      aerial parts of Stachys aegyptiaca afforded a new neoclerodane-type diterpene
      with a new side chain 1, in addition to two known diterpenes 2 and 3 and a known
      flavonoid glycoside 4. The structures of the compounds were determined by
      comprehensive NMR studies including DEPT, COSY, NOESY, HMQC, HMBC and HR-MS. 

PMID- 23972081
TI  - Provision of foot health services for people with rheumatoid arthritis in New
      South Wales: a web-based survey of local podiatrists.
AB  - BACKGROUND: It is unclear if podiatric foot care for people with rheumatoid
      arthritis (RA) in New South Wales (NSW) meets current clinical recommendations.
      The objective of this study was to survey podiatrists' perceptions of the nature
      of podiatric foot care provision for people who have RA in NSW. METHODS: An
      anonymous, cross-sectional survey with a web-based questionnaire was conducted.
      The survey questionnaire was developed according to clinical experience and
      current foot care recommendations. State registered podiatrists practising in the
      state of NSW were invited to participate. The survey link was distributed
      initially via email to members of the Australian Podiatry Association (NSW), and
      distributed further through snowballing techniques using professional networks.
      Data was analysed to assess significant associations between adherence to
      clinical practice guidelines, and private/public podiatry practices. RESULTS: 86
      podiatrists participated in the survey (78% from private practice, 22% from
      public practice). Respondents largely did not adhere to formal guidelines to
      manage their patients (88%). Only one respondent offered a dedicated service for
      patients with RA. Respondents indicated that the primary mode of accessing
      podiatry was by self-referral (68%). Significant variation was observed regarding
      access to disease and foot specific assessments and treatment strategies.
      Assessment methods such as administration of patient reported outcome measures,
      vascular and neurological assessments were not conducted by all respondents.
      Similarly, routine foot care strategies such as prescription of foot orthoses,
      foot health advice and footwear were not employed by all respondents.
      CONCLUSIONS: The results identified issues in foot care provision which should be
      explored through further research. Foot care provision in NSW does not appear to
      meet the current recommended standards for the management of foot problems in
      people who have RA. Improvements to foot care could be undertaken in terms of
      providing better access to examination techniques and treatment strategies that
      are recommended by evidence based treatment paradigms.

PMID- 23972082
TI  - Proton-coupled electron transfers: pH-dependent driving forces? Fundamentals and
      artifacts.
AB  - Besides its own interest, tryptophan oxidation by photogenerated Ru complexes is
      one of the several examples where concerted proton-electron transfer (CPET) to
      water as proton acceptor endowed with a pH-dependent driving force has been
      invoked to explain the data. Since this notion is contrary to the very basic
      principles of chemical physics, it was interesting to attempt uncovering the
      source of this contradiction with an easily accessible substrate. Careful
      examination of the oxidation of the tryptophan (ethyl ester derivative) bearing a
      NH3(+)/NH2 group showed that there is no trace of such an unconventional H2O-CPET
      with a pH-dependent driving force. The reaction mechanism simply consists, with
      both the NH3(+) acid and NH2 basic forms of the tryptophan derivative, in a rate
      determining electron-transfer step followed by deprotonation steps. The same is
      true with the ethyl ester-methyl amide derivative of tryptophan, whose behavior
      is even simpler since the molecule does not bear an acid-base group. No such
      unconventional H2O-CPET was found with phenol, another easily accessible
      substrate. It may thus be inferred that the same applies to less easily available
      systems in which electron transfer occurs intramolecularly. These observations
      help to rid the road of such artificial obstacles and improve present models of
      H2O-CPET reactions, a landmark towards the understanding of the role of water
      chains in natural systems. 

PMID- 23972084
TI  - Best-practice care for people with advanced chronic obstructive pulmonary
      disease: the potential role of a chronic obstructive pulmonary disease care co
      ordinator.
AB  - OBJECTIVE: To explore service availability and accessibility for people with
      advanced chronic obstructive pulmonary disease (COPD) and their carers and
      strategies for improvement, including the potential role of a COPD care co
      ordinator in ensuring best-practice care in the Australian context. METHODS: This
      qualitative study used focus groups and interviews with health professionals,
      carers and consumers to explore gaps and restrictions in services, barriers to
      access and the functioning of services. Data were analysed deductively. RESULTS:
      Key themes arising from the data included difficulties around access to care,
      lack of continuity of care, poor care co-ordination, the need for active disease
      management as well as supportive care, and poor communication. A COPD care co
      ordinator was suggested as an effective strategy for ensuring best-practice care.
      CONCLUSIONS: People with advanced COPD often have difficulty navigating the
      acute, primary and community care systems to deal with the multiple services that
      they may require. Lack of communication between health professionals and services
      is frequently a significant issue. A COPD care co-ordinator, encompassing
      advanced nursing skills, could ensure that care is centred on the needs of the
      person and their carer and that they receive continuing, appropriate and
      accessible care as they approach the end of their life.

PMID- 23972083
TI  - Genome-wide analysis of the AP2/ERF transcription factor superfamily in Chinese
      cabbage (Brassica rapa ssp. pekinensis).
AB  - BACKGROUND: Chinese cabbage (Brassica rapa ssp. pekinensis) is a member of one of
      the most important leaf vegetables grown worldwide, which has experienced
      thousands of years in cultivation and artificial selection. The entire Chinese
      cabbage genome sequence, and more than forty thousand proteins have been obtained
      to date. The genome has undergone triplication events since its divergence from
      Arabidopsis thaliana (13 to 17 Mya), however a high degree of sequence similarity
      and conserved genome structure remain between the two species. Arabidopsis is
      therefore a viable reference species for comparative genomics studies. Variation
      in the number of members in gene families due to genome triplication may
      contribute to the broad range of phenotypic plasticity, and increased tolerance
      to environmental extremes observed in Brassica species. Transcription factors are
      important regulators involved in plant developmental and physiological processes.
      The AP2/ERF proteins, one of the most important families of transcriptional
      regulators, play a crucial role in plant growth, and in response to biotic and
      abiotic stressors. Our analysis will provide resources for understanding the
      tolerance mechanisms in Brassica rapa ssp. pekinensis. RESULTS: In the present
      study, 291 putative AP2/ERF transcription factor proteins were identified from
      the Chinese cabbage genome database, and compared with proteins from 15
      additional species. The Chinese cabbage AP2/ERF superfamily was classified into
      four families, including AP2, ERF, RAV, and Soloist. The ERF family was further
      divided into DREB and ERF subfamilies. The AP2/ERF superfamily was subsequently
      divided into 15 groups. The identification, classification, phylogenetic
      reconstruction, conserved motifs, chromosome distribution, functional annotation,
      expression patterns, and interaction networks of the AP2/ERF transcription factor
      superfamily were predicted and analyzed. Distribution mapping results showed
      AP2/ERF superfamily genes were localized on the 10 Chinese cabbage chromosomes.
      AP2/ERF transcription factor expression levels exhibited differences among six
      tissue types based on expressed sequence tags (ESTs). In the AP2/ERF superfamily,
      214 orthologous genes were identified between Chinese cabbage and Arabidopsis.
      Orthologous gene interaction networks were constructed, and included seven CBF
      and four AP2 genes, primarily involved in cold regulatory pathways and ovule
      development, respectively. CONCLUSIONS: The evolution of the AP2/ERF
      transcription factor superfamily in Chinese cabbage resulted from genome
      triplication and tandem duplications. A comprehensive analysis of the
      physiological functions and biological roles of AP2/ERF superfamily genes in
      Chinese cabbage is required to fully elucidate AP2/ERF, which provides us with
      rich resources and opportunities to understand crop stress tolerance mechanisms.

PMID- 23972085
TI  - Chemotherapy for the treatment of malignant peripheral nerve sheath tumors in
      neurofibromatosis 1: a 10-year institutional review.
AB  - BACKGROUND: Neurofibromatosis 1 (NF1) is the most common autosomal dominant
      disorder, with an incidence of 1 in 2,500-3,300 live births. NF1 is associated
      with significant morbidity and mortality because of complications, especially
      malignant peripheral nerve sheath tumors (MPNSTs), which mainly develop during
      adulthood. We evaluated our experience with management of NF1 with MPNSTs by
      standard chemotherapy with anthracycline and/or ifosfamide in terms of time to
      treatment failure and overall survival. METHODS: We performed a retrospective
      review of consecutive patients with NF1 and a diagnosis of MPNSTs between 1993
      and 2003 in our referral center for NF1. Prognostic factors were evaluated by
      univariate analysis. RESULTS: We evaluated data for 21 patients with grade 1
      (n=1), grade 2 (n=8) and grade 3 (n=12) MPNST; 16 presented localized disease and
      underwent surgery: margins for 6 were tumor-free (including 3 patients with
      amputation), 2 showed microscopic residual disease and 8 showed macroscopic
      residual disease. All patients received chemotherapy and 9 radiotherapy. Median
      time to treatment failure and overall survival were 7.8 and 17 months,
      respectively. Two patients were still alive at 138 and 167 months. We found no
      significant relationship between type of chemotherapy and time to treatment
      failure or overall survival. CONCLUSIONS: MPNSTs are highly aggressive in NF1.
      Conventional chemotherapy does not seem to reduce mortality, and its role must be
      questioned. Recent advances in the molecular biology of MPNSTs may provide new
      prognostic factors and targeted therapies.

PMID- 23972086
TI  - Aqueous soluble vascular endothelial growth factor receptor-2 in macular edema
      with branch retinal vein occlusion.
AB  - PURPOSE/AIM: The aqueous humor level of soluble vascular endothelial growth
      factor receptor (sVEGFR)-2 may influence macular edema in patients with branch
      retinal vein occlusion (BRVO). The association of sVEGFR-2 with macular edema was
      investigated in this study. MATERIALS AND METHODS: A retrospective case
      controlled study was performed in 22 patients with BRVO and macular edema, as
      well as 5 patients with non-ischemic ocular diseases as the control group. The
      severity of macular edema was examined by optical coherence tomography. Aqueous
      humor samples were obtained during intravitreous injection of anti-VEGF agents,
      triamcinolone acetonide, or combined vitrectomy and cataract surgery. sVEGFR-2
      levels in aqueous humor were determined by enzyme-linked immunosorbent assay.
      RESULTS: The aqueous humor level of sVEGFR-2 (median: 124.5 ng/ml) was
      significantly elevated in BRVO patients compared with the control group (78.1
      pg/ml) (p = 0.010). In addition, the sVEGFR-2 level was correlated with the
      severity of macular edema (p = 0.033). CONCLUSIONS: sVEGFR-2 may be involved in
      the pathogenesis of macular edema associated with BRVO. Measurement of aqueous
      humor sVEGFR-2 levels may be helpful for understanding the disease status in BRVO
      patients with macular edema.

PMID- 23972087
TI  - Cognitive neuroscience analyses of memory: a historical perspective.
AB  - As part of the general trend toward interdisciplinary research in recent years, a
      growing number of investigators have come to consider both cognitive and
      neuroscientific perspectives when theorizing about memory. Although such
      cognitive neuroscience analyses are a relatively recent development, the approach
      has precedents in earlier scientific thinking about memory. In this article we
      present a historical review of three major issues in memory research--
      consolidation processes, the nature of memory representations, and multiple
      memory systems. We discuss the nature of the relation between cognitive and
      neuroscientific approaches to each of these issues with respect to the
      distinction between collateral, complementary, and convergent relations
      (Schacter, 1986). Although some early investigators offered analyses that linked
      psychological and physiological perspectives, there is little historical evidence
      of systematic or sustained interdisciplinary research. However, more recent work,
      especially with respect to hypotheses about memory systems, suggests progress
      toward establishing programmatic interdisciplinary research. 

PMID- 23972088
TI  - Preserved priming of novel objects in patients with memory disorders.
AB  - Amnesic patients perform poorly on explicit memory tests that require conscious
      recollection of recent experiences, but frequently show preserved facilitations
      of performance or priming effects on implicit memory tasks that do not require
      conscious recollection. We examined implicit memory for novel visual objects on
      an object decision test in which subjects decide whether structurally possible
      and impossible objects could exist in three-dimensional form. Patients with
      organic memory disorders showed robust priming effects on this task---object
      decision accuracy was higher for previously studied objects than for nonstudied
      objects---and the magnitude of priming did not differ from matched control
      subjects or college students. However, patients showed impaired explicit memory
      for novel visual objects on a recognition test. We argue that priming is mediated
      by the structural description system, a subsystem of the perceptual
      representation system, that operates at a presemantic level and is preserved in
      amnesic patients. 

PMID- 23972089
TI  - Fractionating the word repetition effect with event-related potentials.
AB  - Word repetition has been a staple paradigm for both psycholinguistic and memory
      research; several possible loci for changes in behavioral performance have been
      proposed. These proposals are discussed in light of the event-related brain
      potential (ERP) data reported here. ERPs were recorded as subjects read
      nonfiction articles drawn from a popular magazine. The effects of word repetition
      were examined in this relatively natural context wherein words were repeated as a
      consequence of normal discourse structure. Three distinct components of the ERP
      were found to be sensitive to repetition: a positive component peaking at 200
      msec poststimulus, a negative one at 400 msec (N400), and a later positivity. The
      components were differentially sensitive to the temporal lag between repetitions,
      the number of repetitions, and the normative frequency of the eliciting word. The
      N400 responded similarly to repetition in text as it has in experimental lists of
      words, but the late positivity showed a different pattern of results than in list
      studies. 

PMID- 23972090
TI  - Syntactically based sentence processing classes: evidence from event-related
      brain potentials.
AB  - Theoretical considerations and diverse empirical data from clinical,
      psycholinguistic, and developmental studies suggest that language comprehension
      processes are decomposable into separate subsystems, including distinct systems
      for semantic and grammatical processing. Here we report that event-related
      potentials (ERPs) to syntactically well-formed but semantically anomalous
      sentences produced a pattern of brain activity that is distinct in timing and
      distribution from the patterns elicited by syntactically deviant sentences, and
      further, that different types of syntactic deviance produced distinct ERP
      patterns. Forty right-handed young adults read sentences presented at 2 words/sec
      while ERPs were recorded from over several positions between and within the
      hemispheres. Half of the sentences were semantically and grammatically acceptable
      and were controls for the remainder, which contained sentence medial words that
      violated (1) semantic expectations, (2) phrase structure rules, or (3) WH
      movement constraints on Specificity and (4) Subjacency. As in prior research, the
      semantic anomalies produced a negative potential, N400, that was bilaterally
      distributed and was largest over posterior regions. The phrase structure
      violations enhanced the N125 response over anterior regions of the left
      hemisphere, and elicited a negative response (300-500 msec) over temporal and
      parietal regions of the left hemisphere. Violations of Specificity constraints
      produced a slow negative potential, evident by 125 msec, that was also largest
      over anterior regions of the left hemisphere. Violations of Subjacency
      constraints elicited a broadly and symmetrically distributed positivity that
      onset around 200 msec. The distinct timing and distribution of these effects
      provide biological support for theories that distinguish between these types of
      grammatical rules and constraints and more generally for the proposal that
      semantic and grammatical processes are distinct subsystems within the language
      faculty. 

PMID- 23972091
TI  - Alzheimer's disease effects on semantic memory: loss of structure or impaired
      processing?
AB  - Results of several prior studies, in which Alzheimer's disease (AD) patients
      missed the same concepts on multiple tasks, have been used to substantiate the
      theory that AD causes concept-specific loss of information from semantic memory
      However, sample sizes in these studies are modest, test-retest intervals small,
      and typically only a few tasks were used. In the present study 69 An subjects
      were annually administered 11 tasks, each using the same 13 concepts. Only a few
      instances were observed in which a concept was missed across all 11 tasks. When
      performances on the Oral Reading and Dictation tasks were removed from analysis,
      because of their questionable reliance on semantic memory, the number of missed
      concepts rose only modestly. A substantial rise in the number of missed concepts
      occurred, however, when performances on the four multiple- choice tasks were
      removed. Interpreting the larger number of missed concepts on the five remaining
      generative semantic tasks as evidence of item-specific loss is problematic,
      nonetheless, because the generative semantic tasks were among the hardest in the
      battery and the frequency with which an individual subject missed a concept
      across all tasks accorded with the subject's dementia severity level. Results
      also indicate that task difficulty, more than concept specificity, determine
      whether a concept is missed. Overall, results suggest that a concept will
      "disappear" when all of the tasks in which it is a stimulus become too difficult
      for the patient to perform. Study results call into question the appropriateness
      of using batteries of effortful, attention demanding tasks for ascertaining
      whether AD causes item-specific loss of conceptual knowledge. 

PMID- 23972092
TI  - When metacognition fails: impaired awareness of deficit in Alzheimer's disease.
AB  - Two new measures were developed to assess quantitatively the degree to which
      patients with Alzheimer's disease (AD) are aware of their memory deficit, and to
      evaluate the relation between dementia severity and awareness of deficit. Results
      of a questionnaire measure indicated that AD patients rated their own
      difficulties with cognitive activities of daily life significantly lower than
      relatives rated patients' problems, and this discrepancy was related to patients'
      dementia severity. On another measure involving task performance predictions, AD
      patients were inaccurate in predicting their performance on most cognitive tasks
      when compared to both their actual performance and relatives' predictions,
      despite generally accurate prediction of their relatives' performance on the same
      tasks. These results are discussed in terms of a breakdown in metacognitive
      processes. 

PMID- 23972093
TI  - "Dead reckoning," landmark learning, and the sense of direction: a
      neurophysiological and computational hypothesis.
AB  - Behavioral and neurophysiological evidence strongly suggests that, within certain
      limits, rodents and humans can keep track of their directional heading relative
      to an inertial, and hence allocentric coordinate system. This "sense of
      direction" appears to involve the integration of angular velocity signals that
      arise primarily in the vestibular system. A hypothesis is proposed in which the
      integration process, an operation that may be difficult for neurons to implement,
      is replaced by a linear associative mapping, an operation that is at least
      theoretically easy to implement with neurons. The proposed system makes use of a
      set of linearly independent vectors representing the combination of the current
      head direction, and head angular velocity representations to "recall" the
      resulting head direction. It is then proposed that visual landmarks become
      incorporated into the directional system, enabling both the correction of
      cumulative error and, ultimately, the computation of novel, optimal trajectories
      between locations. According to the hypothesis, this occurs through the
      association of hippo-campal "local-view" cells (i.e., direction selective "place
      cells") with "head-direction" cells located downstream in the dorsal
      presubiculum. The possible neurophysiological and neuroan-atomical bases for the
      proposed system are discussed. 

PMID- 23972094
TI  - Correspondence effects with torches: grasping affordance or visual feature
      asymmetry?
AB  - Three experiments were conducted to determine whether an object-based
      correspondence effect for torch (flashlight) stimuli reported by Pellicano et al.
      [( 2010 ). Simon-like and functional affordance effects with tools: The effects
      of object perceptual discrimination and object action state. Quarterly Journal of
      Experimental Psychology, 63, 2190-2201] is due to a grasping affordance provided
      by the handle or asymmetry of feature markings on the torch. In Experiment 1 the
      stimuli were the same as those from Pellicano et al.'s Experiment 2, whereas in
      Experiments 2 and 3 the stimuli were modified versions with the graspable handle
      removed. Participants in all experiments performed upright/inverted orientation
      judgements on the torch stimuli. The results of Experiment 1 replicated those of
      Pellicano et al.: A small but significant object-based correspondence effect was
      evident, mainly when the torch was in an active state. With the handle of the
      torch removed in Experiment 2, making the barrel markings more asymmetric in the
      display, the correspondence effect was larger. Experiment 3 directly demonstrated
      an effect of barrel-marking asymmetry on the correspondence effect: When only the
      half of the markings nearest the light end of the torch was included, the
      correspondence effect reversed to favour the light end. The results are in
      agreement with a visual feature-asymmetry account and are difficult to reconcile
      with a grasping-affordance account.

PMID- 23972095
TI  - Raman spectroscopy-an innovative and versatile tool to follow the respirational
      activity and carbonate biomineralization of important cave bacteria.
AB  - Raman gas spectrometry is introduced as a unique tool for the investigation of
      the respiratory activity that is indicative for growth of bacteria involved in
      biomineralization. Growth of these bacteria cannot be monitored using
      conventional turbidity-based optical density measurements due to concomitant
      mineral formation in the medium. The respiratory activity of carbonate
      precipitating Arthrobacter sulfonivorans , isolated from the recently discovered
      Herrenberg Cave, was investigated during its lifecycle by means of innovative
      cavity-enhanced Raman gas analysis. This method allowed rapid and nonconsumptive
      online quantification of CO2 and O2 in situ in the headspace of the bacterial
      culture. Carbon dioxide production rates of A. sulfonivorans showed two maxima
      due to its pleomorphic growth lifecycle. In contrast, only one maximum was
      observed in control organism Pseudomonas fluorescens with a one-stage lifecycle.
      Further insight into the biomineralization process over time was provided by a
      combination of Raman macro- and microspectroscopy. With the help of this
      spatially resolved chemical imaging of the different types of calcium carbonate
      minerals, it was elucidated that the surface of the A. sulfonivorans bacterial
      cells served as nuclei for biomineralization of initially spherical vaterite
      precipitates. These vaterite biominerals continued growing as chemically stable
      rock-forming calcite crystals with rough edges. Thus, the utilization of
      innovative Raman multigas spectroscopy, combined with Raman mineral analysis,
      provided novel insights into microbial-mediated biomineralization and, therefore,
      provides a powerful methodology in the field of environmental sciences. 

PMID- 23972096
TI  - Primary malignant melanoma of the esophagus: a rare and aggressive disease.
AB  - Primary malignant melanoma of the esophagus is an uncommon tumor, with
      approximately 300 cases having been reported thus far. The purpose of this study
      was to describe a case of a 60 year-old man with a 10 month history of
      progressive dysphagia and thoracic pain, the investigations of which led to a
      diagnosis of primary malignant melanoma of the esophagus. The patient underwent a
      transhiatal esophagectomy with subcarinal lymphadenectomy, and isoperistaltic
      gastric tube replacement of the esophagus. Nine months after surgery, he
      developed ischemic colitis, and metastasis in the mesentery was diagnosed. His
      disease progressed and he died one year after the esophagectomy. A review of the
      literature was performed. 

PMID- 23972097
TI  - The contribution of practice skills in a care management process for family
      caregivers.
AB  - Practice skills are believed to improve practice, yet, little is known about the
      extent to which skills affect outcomes. This exploratory study examined the
      extent to which 3 practice skills specific to a care management context for
      family caregivers, including communication skills, supportive skills, and linking
      skills, were associated with fidelity of a care management process. Twenty-one
      care managers who used a single process to serve 113 family caregivers were
      included in the study. Bivariate correlation analysis revealed the 3 practice
      skills are positively associated with process fidelity. Implications for social
      work practice, education, and research are discussed. 

PMID- 23972098
TI  - DNA sequences that interfere with transcription: implications for genome function
      and stability.

PMID- 23972099
TI  - Evaluation of WO2013076170: the use of a dihydroorotate dehydrogenase inhibitor
      for the treatment of psoriasis.
AB  - Inhibition of dihydroorotate dehydrogenase (DHODH) modulates pyrimidine
      biosynthesis. Effective inhibitors are immunomodulatory drugs clinically useful
      in the treatment of diseases such as rheumatoid arthritis, psoriatic arthritis
      and multiple sclerosis. There is limited evidence of their potential utility in
      treating psoriasis. This patent application claims topical formulations of the
      non-hepatotoxic DHODH inhibitor 2-[(3,5-difluoro-3'-methoxy-1,1'-biphenyl-4
      yl)amino]nicotinic acid for use in the treatment of psoriasis. This inhibitor had
      previously been claimed to be useful in treating various autoimmune disease. 

PMID- 23972100
TI  - Molecular epidemiology of early and acute HIV type 1 infections in the United
      States Navy and Marine Corps, 2005-2010.
AB  - The U.S. military represents a unique population within the human
      immunodeficiency virus 1 (HIV-1) pandemic. The last comprehensive study of HIV-1
      in members of the U.S. Navy and Marine Corps (Sea Services) was completed in
      2000, before large-scale combat operations were taking place. Here, we present
      molecular characterization of HIV-1 from 40 Sea Services personnel who were
      identified during their seroconversion window and initially classified as HIV-1
      negative during screening. Protease/reverse transcriptase (pro/rt) and envelope
      (env) sequences were obtained from each member of the cohort. Phylogenetic
      analyses were carried out on these regions to determine relatedness within the
      cohort and calculate the most recent common ancestor for the related sequences.
      We identified 39 individuals infected with subtype B and one infected with
      CRF01_AE. Comparison of the pairwise genetic distance of Sea Service sequences
      and reference sequences in the env and pro/rt regions showed that five samples
      were part of molecular clusters, a group of two and a group of three, confirmed
      by single genome amplification. Real-time molecular monitoring of new HIV-1
      acquisitions in the Sea Services may have a role in facilitating public health
      interventions at sites where related HIV-1 infections are identified.

PMID- 23972101
TI  - Sound symbolism in synesthesia: evidence from a lexical-gustatory synesthete.
AB  - Synesthesia is a condition in which perceptual or cognitive stimuli (e.g., a
      written letter) trigger atypical additional percepts (e.g., the color yellow).
      Although these cross-modal pairings appear idiosyncratic in that they
      superficially differ from synesthete to synesthete, underlying patterns do exist
      and these can, in some circumstances, reflect the cross-modal intuitions of
      nonsynesthetes (e.g., higher pitch sounds tend to be "seen" in lighter colors by
      synesthetes and are also paired to lighter colors by nonsynesthetes in cross
      modal matching tasks). We recently showed that grapheme-color synesthetes are
      more sensitive to sound symbolism (i.e., cross-modal sound-meaning
      correspondences) in natural language compared to nonsynesthetes. Accordingly, we
      hypothesize that sound symbolism may be a guiding force in synesthesia to dictate
      what types of synesthetic experiences are triggered by words. We tested this
      hypothesis by examining the cross-modal mappings of lexical-gustatory synesthete,
      JIW, for whom words trigger flavor experiences. We show that certain phonological
      features (e.g., front vowels) systematically trigger particular categories of
      taste (e.g., bitter) in his synesthesia. Some of these associations agree with
      sound symbolic patterns in natural language. This supports the view that
      synesthesia may be an exaggeration of cross-modal associations found in the
      general population and that sound symbolic properties of language may arise from
      similar mechanisms as those found in synesthesia. 

PMID- 23972102
TI  - Grasping the experience of the other from an interview: self-transposition in
      use.
AB  - This article describes a part of the interview process that is never usually
      reported. Listening to what people say is the key to increasing our knowledge of
      human existences. Procuring knowledge about human experience is much more
      challenging. Although good sources on how to prepare and conduct an interview
      exist, the process of the interviewer's perception of the interviewee's message
      and meaning is less examined. Beyond the role of eliciting the data, the
      researcher endeavours to reproduce the interviewee's narration and not the voice
      of the researcher. By illustrating the process during the interview, further
      transparency and thereby validity may be achieved. To exemplify this, the
      perception of the interviewer is explored, and here Heidegger's work on self
      transposition has proved to be helpful. 

PMID- 23972103
TI  - Metabolites of Streptomyces sp., an endophytic actinomycete from Alpinia
      oxyphylla.
AB  - Four known compounds had been isolated from the Streptomyces sp. YIM66017, and
      their structures were elucidated by spectral analysis as 2,6-dimethoxy
      terephthalic acid (1), yangjinhualine A (2), alpha-hydroxyacetovanillone (3) and
      cyclo(Gly-Trp) (4). Compound 1 was isolated from natural resources for the first
      time, and compounds 2-4 were isolated from streptomycetes for the first time. The
      2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity assays showed that 1
      showed higher activity than rutin with IC50 of 4.61 MUg/mL and 2 showed the
      activity with IC50 of 57.12 MUg/mL. 

PMID- 23972104
TI  - Depression in primary care: what more do we need to know?

PMID- 23972105
TI  - Depression in primary care: current and future challenges.
AB  - OBJECTIVES: To describe the current state of knowledge about detection and
      treatment of major depressive disorder (MDD) by family physicians (FPs), and to
      identify gaps in practice and current and future challenges. METHODS: We reviewed
      the recent literature on MDD (Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, or International Classification of Diseases, Revision
      10) in primary care, with an emphasis on systematic reviews and meta-analyses
      addressing prevalence, the impact of an aging population and of chronic disease
      on MDD rates in primary care, detection and treatment rates by FPs, adequacy of
      treatment, and interventions that could improve recognition and treatment.
      RESULTS: About 10% of primary care patients are likely to meet criteria for MDD.
      The number of cases will increase as the baby boomer cohort ages and as the
      prevalence of chronic disease increases. The bidirectional relation between MDD
      and chronic disease is now firmly established. Detection and treatment rates in
      primary care remain low. Treatment quality is frequently inadequate in terms of
      follow-up and monitoring. Formal case management and collaborative care
      interventions are likely to provide some benefits. CONCLUSIONS: Low detection
      rates and low treatment rates need to be addressed. Planned reassessment may
      improve detection rates when the FP is uncertain whether MDD is present, but
      further research is needed to determine why FPs frequently do not initiate
      treatment, even when MDD is detected. A caring, attentive FP who monitors
      depressed patients is likely to have considerable placebo effect. Greater focus
      on integrated, concurrent treatment for MDD and chronic physical diseases in the
      middle-aged and elderly is also required.

PMID- 23972106
TI  - Educating family physicians to recognize and manage depression: where are we now?
AB  - OBJECTIVES: To consider what the barriers are to effective depression education;
      to understand what attitudes, knowledge, and skills doctors need to acquire, and
      finally to examine what we currently know about effective ways of training family
      physicians (FPs) about depression. METHODS: A narrative review of the published
      literature compiled from searching reviews and original articles was conducted
      using the following key words: education, training, attitudes, depression, and
      primary care. Further relevant articles were identified from reference lists.
      RESULTS: The identified barriers are FPs' attitudes and confidence toward
      recognizing and managing depression, the way in which they conceptualize
      depression, and the difficulties they face in implementing change in the systems
      in which they work. We, as educators, can identify what FPs need to know, and
      this should include novel ways of organizing care. However, of key importance is
      the need to address how more effective interventions may be provided, recognizing
      that FPs may be starting from many different points on 3 differing continua of
      attitude, skills, and knowledge in relation to depression. CONCLUSIONS: We have
      to not only ensure that the content of what we teach is perceived as relevant to
      primary care but also review exactly how we go about providing it, using methods
      that will engage and stimulate doctors at differing stages of readiness to
      acquire new attitudes, skills, and knowledge about depression. However, we still
      need to find better ways of helping FPs to recognize and acknowledge their
      educational needs. Further research is also required to thoroughly evaluate these
      novel approaches to tailoring educational interventions.

PMID- 23972107
TI  - The adequacy of pharmaceutical treatment of schizophrenia in Quebec varies with
      age, but is not influenced by sex or neighbourhood deprivation.
AB  - OBJECTIVE: Though high discontinuation rates for antipsychotics (APs) by patients
      with schizophrenia are frequently reported, the percentage of patients receiving
      pharmaceutical treatment for schizophrenia in routine practice in accordance with
      international clinical guidelines is unknown. Further, it is unknown if these
      rates are influenced by levels of neighbourhood deprivation or by a patient's age
      or sex. Our study aims to investigate if inequalities in AP treatment could be
      observed between patients living in neighbourhoods with the highest levels of
      material and social deprivation and those with the lowest deprivation levels,
      between patients from different age groups, or between men and women. METHODS: We
      conducted a secondary analysis of medical-administrative data of a cohort of
      adult patients in the province of Quebec with a medical contact for schizophrenia
      in a 2-year period (2004-2005). We assessed the proportion of patients that
      filled at least 1 prescription for an AP and received adequate pharmaceutical
      treatment, defined as being in possession of APs at least 80% of the time as
      outpatients during a 2-year follow-up period. RESULTS: Among the 30 544 study
      patients, 88.5% filled at least 1 prescription for an AP, and 67.5% of the
      treated patients received adequate treatment. Though no clinically significant
      differences were observed by deprivation or sex, younger age was associated with
      lower proportions of patients receiving adequate treatment (46% of treated
      patients aged between 18 and 29 years, compared with 72% aged between 30 and 64
      years, and 77% aged 65 years and over). CONCLUSIONS: In Quebec's routine
      practice, over 70% of treated patients aged 30 and over received adequate
      pharmacological treatment, regardless of sex or neighbourhood socioeconomic
      status. In contrast, in patients aged between 18 and 29 years this percentage was
      47%. This is a discouraging finding, especially because optimal treatment in the
      early phase of disease is reported to result in the best long-term outcomes.

PMID- 23972108
TI  - Reliability, validity, and clinical use of the Dominic Interactive: a DSM-based,
      self-report screen for school-aged children.
AB  - OBJECTIVES: As no single informant can be considered the gold standard of child
      psychopathology, interviewing of children regarding their own symptoms is
      necessary. Our study focused on the reliability, validity, and clinical use of
      the Dominic Interactive (DI), a multimedia self-report screen to assess symptoms
      for the most frequent Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition, Text Revision, mental disorders in school-aged children. METHODS:
      A sample of 585 children aged 6 to 11 years from the community and psychiatric
      clinics was used to analyze the internal consistency, the test-retest estimate of
      reliability, and the criterion-related validity of the DI against the referral
      status. In addition, cross-informant correlation coefficients between this
      instrument (child report) and the Child Symptom Inventory (parent report) were
      explored in a subsample of 292 participants. RESULTS: For the total sample,
      Cronbach alpha coefficients ranged from 0.63 to 0.91. Test-retest kappas varied
      from 0.42 to 0.62 for categories based on cut-off points, except for specific
      phobias. Intraclass correlation coefficients ranged from 0.70 to 0.81 for symptom
      scales. The DI discriminated between referred and non-referred children in
      psychiatric clinics for all symptom scales. Significant cross-informant
      correlation coefficients were higher for the externalizing symptoms (0.35 to
      0.48) than the internalizing symptoms (0.14 to 0.27). CONCLUSIONS: Findings of
      our study reasonably support adequate psychometric properties of the DI. This
      instrument offers a developmentally sensitive screening method to obtain unique
      information from young children about their mental health problems in front-line
      services, psychiatric clinics, and research settings.

PMID- 23972109
TI  - Within-hospital readmission: an indicator of readmission after discharge from
      psychiatric hospitalization.
AB  - OBJECTIVE: Readmission after psychiatric hospitalization is widely used as a
      quality of care indicator by government funding agencies, policy-makers, and
      hospitals deciding on clinical priorities. Readmission rates are calculated
      accurately to allow these varied groups to correctly translate the knowledge into
      appropriate, tangible outcomes. We aimed to assess how well hospital readmission
      rates, calculated using only readmissions to the discharging institution, can
      approximate actual readmission rates. METHOD: We used administrative data sources
      to identify patients with a mental health discharge in the province of Ontario
      (2008-2011). We identified mental health readmissions within 30 and 90 days of
      discharge occurring to the hospital from which the patient was discharged (within
      hospital readmissions), and compared readmission rates using only within-hospital
      admissions with actual readmission rates. RESULTS: The percentage of readmissions
      occurring to the discharging institution ranged from 39% to 89% (median 73%) and
      from 37% to 86% (median 70%) for 30- and 90-day readmissions, respectively. Using
      only within-hospital readmissions to rank hospitals by their readmission rates,
      only 56% of hospitals for 30-day readmissions and 50% for 90-day readmissions
      were ranked in the same quartile as when actual readmission rates were used.
      CONCLUSIONS: These findings highlight the importance of measuring psychiatric
      readmissions at the system level, particularly for hospitals with lower discharge
      volumes. As well, the high likelihood that multiple hospitals are involved in the
      hospital-based care of people who require readmission requires consideration at
      clinical and policy levels.

PMID- 23972110
TI  - Psychosocial interventions for bipolar disorder and coping style modification:
      similar clinical outcomes, similar mechanisms?
AB  - OBJECTIVE: To investigate changes in the use of coping styles in response to
      early symptoms of mania in cognitive-behavioural therapy (CBT), compared with
      psychoeducation, for bipolar disorder. METHOD: Data were drawn from a randomized
      controlled trial comparing CBT and psychoeducation. A subsample of 119
      participants completed the Coping Inventory for the Prodromes of Mania and
      symptom assessments before treatment and 72 weeks later. RESULTS: Both CBT and
      psychoeducation were associated with similar improvements in symptom burden. Both
      treatments also produced equivalent improvements in stimulation reduction and
      problem-directed coping styles, but no statistically significant change on the
      endorsement of help-seeking behaviours. A treatment interaction showed that a
      reduction in denial and blame was present only in the CBT treatment condition.
      CONCLUSIONS: CBT and psychoeducation have similar impacts on coping styles for
      the prodromes of mania. The exception to this is denial and blame, which is
      positively impacted only by CBT but which does not translate into improved
      outcome. Given the similar change in coping styles and mood burden, teaching
      patients about how to cope in adaptive ways with the symptoms of mania may be a
      shared mechanism of change for CBT and psychoeducation. CLINICAL TRIAL
      REGISTRATION NUMBER: NCT00188838.

PMID- 23972111
TI  - Childhood maltreatment and aggressive behaviour in violent offenders with
      psychopathy.
AB  - OBJECTIVE: To document experiences of childhood maltreatment among violent
      offenders with antisocial personality disorder (ASPD) distinguishing between
      those with and without the syndrome of psychopathy (+P and -P), and to determine
      whether maltreatment is associated with proactive and reactive aggression.
      METHOD: The sample included 10 violent offenders with ASPD+P, 15 violent
      offenders with ASPD-P, and 15 non offenders. All participants completed
      interviews with the same forensic psychiatrist focusing on physical, sexual, and
      emotional abuse prior to age 18 using the Early Trauma Inventory. Aggression was
      assessed using the Reactive-Proactive Questionnaire. RESULTS: Violent offenders
      with ASPD+P reported significantly more severe childhood physical abuse, but not
      more sexual or emotional abuse, than violent offenders with ASPD-P and non
      offenders. Psychopathy Checklist-Revised (PCL-R) scores, but not childhood
      physical abuse, were associated with proactive aggression. Childhood physical
      abuse was associated with reactive aggression, as was an interaction term
      indicating that when both PCL-R scores and childhood physical abuse were high, so
      was reactive aggression. CONCLUSIONS: Among violent offenders, PCL-R scores were
      positively associated with proactive aggression, while experiences of childhood
      maltreatment were not. This finding concurs with previous studies of children and
      adults and suggests that proactive aggression may be a behavioural marker of
      psychopathic traits. By contrast, childhood physical abuse was associated with
      reactive aggression, even among violent offenders with high PCL-R scores. This
      latter finding suggests a strong influence of childhood physical abuse on the
      development of reactive aggression that persists over the lifespan.

PMID- 23972112
TI  - Management of diabetes mellitus and associated cardiovascular risk factors in
      Brazil - the Brazilian study on the practice of diabetes care.
AB  - BACKGROUND: The Brazilian Study on the Practice of Diabetes Care main objective
      was to provide an epidemiological profile of individuals with type 1 and 2
      diabetes mellitus (DM) in Brazil, concerning therapy and adherence to
      international guidelines in the medical practice. METHODS: This observational,
      cross-sectional, multicenter study collected and analyzed data from individuals
      with type 1 and 2 DM attending public or private clinics in Brazil. Each
      investigator included the first 10 patients with type 2 DM who visited his/her
      office, and the first 5 patients with type 1 DM. RESULTS: A total of 1,358
      patients were analyzed; 375 (27.6%) had type 1 and 983 (72.4%) had type 2 DM.
      Most individuals were women, Caucasian, and private health care users. High
      prevalence rates of hypertension, dyslipidemia and central obesity were observed,
      particularly in type 2 DM. Only 7.3% and 5.1% of the individuals with types 1 and
      2 DM, respectively, had optimal control of blood pressure, plasma glucose and
      lipids. The absence of hypertension and female sex were associated with better
      control of type 1 DM and other cardiovascular risk factors. In type 2 DM, older
      age was also associated with better control. CONCLUSIONS: Female sex, older age,
      and absence of hypertension were associated with better metabolic control. An
      optimal control of plasma glucose and other cardiovascular risk factors are
      obtained only in a minority of individuals with diabetes. Local numbers, compared
      to those from other countries are worse.

PMID- 23972114
TI  - Synthesis of (+/-)-actinophyllic acid and analogs: applications of cascade
      reactions and diverted total synthesis.
AB  - Actinophyllic acid is a biologically active indole alkaloid with a unique
      structural framework that incorporates five contiguous stereocenters. A total
      synthesis of (+/-)-actinophyllic acid has been completed that proceeds in only 10
      steps from readily available, known compounds and with the isolation of nine
      intermediates. The synthesis features a novel cascade of reactions of N
      stabilized carbocations with pi-nucleophiles to create the tetracyclic core of
      actinophyllic acid in a single chemical operation. This pivotal cascade sequence
      generates substructures of the actinophyllic acid core that are not otherwise
      accessible, and one key intermediate was modified to furnish several novel
      compounds having potentially promising anticancer activity, one of which induces
      cell death in a wide range of cancer cell lines. 

PMID- 23972113
TI  - Effects of hypoxanthine substitution in peptide nucleic acids targeting KRAS2
      oncogenic mRNA molecules: theory and experiment.
AB  - Genetic disorders can arise from single base substitutions in a single gene. A
      single base substitution for wild type guanine in the twelfth codon of KRAS2 mRNA
      occurs frequently to initiate lung, pancreatic, and colon cancer. We have
      observed single base mismatch specificity in radioimaging of mutant KRAS2 mRNA in
      tumors in mice by in vivo hybridization with radiolabeled peptide nucleic acid
      (PNA) dodecamers. We hypothesized that multimutant specificity could be achieved
      with a PNA dodecamer incorporating hypoxanthine, which can form Watson-Crick base
      pairs with adenine, cytosine, thymine, and uracil. Using molecular dynamics
      simulations and free energy calculations, we show that hypoxanthine substitutions
      in PNAs are tolerated in KRAS2 RNA:PNA duplexes where wild type guanine is
      replaced by mutant uracil or adenine in RNA. To validate our predictions, we
      synthesized PNA dodecamers with hypoxanthine, and then measured the thermal
      stability of RNA:PNA duplexes. Circular dichroism thermal melting results showed
      that hypoxanthine-containing PNAs are more stable in duplexes where hypoxanthine
      adenine and hypoxanthine-uracil base pairs are formed than single mismatch
      duplexes or duplexes containing hypoxanthine-guanine opposition. 

PMID- 23972116
TI  - Neurophysiological Manifestations of Recollective Experience during Recognition
      Memory Judgments.
AB  - Abstract Decisions regarding whether an item has been previously encountered are
      typically accompanied by one of two distinct forms of subjective awareness:
      either a general sense of familiarity, or conscious recollection of specific
      details from a prior study episode. To examine the neurophysiological
      concomitants of these different types of internal experience, event-related
      potentials (ERPs) were recorded while subjects engaged in a modified recognition
      memory procedure that required them to describe their subjective response during
      each testtrial. Stimuli that evoked recollection were accompanied by waveforms
      distinct from those that evoked only a sense of familiarity, and waveforms for
      both categories of correctly classified old items differed from correctly
      rejected distractor items and incorrectly classified (missed) studied items.
      These ERP responses are interpreted with respect to current knowledge concerning
      the neural structures and processes intimately involved in the capacity to engage
      in recollection. 

PMID- 23972115
TI  - Patients' experiences of referral for colorectal cancer.
AB  - BACKGROUND: Outcomes for colorectal cancer patients vary significantly. Compared
      to other countries, Australia has a good record with patient outcomes, yet there
      is little information available on the referral pathway. This paper explores the
      views of Australian patients and their experiences of referral for colorectal
      cancer treatment following diagnosis; the aim was to improve our understanding of
      the referral pathway and guide the development of future interventions. METHODS:
      A purposive sampling strategy was used, recruiting 29 patients representing urban
      and rural areas from 3 Australian states who participated in 4 focus groups.
      Seven patients provided individual interviews to supplement the data. Recordings
      were transcribed verbatim, data was coded with NVivo software and analysed
      thematically before deductive analysis. RESULTS: Four aspects of the referral
      process were identified by patients, namely detection/diagnosis, referral for
      initial treatment/specialist care, the roles of the GP/specialist, and the
      patient's perceived involvement in the process. The referral process was
      characterised by a lack of patient involvement, with few examples of shared
      decision-making and few examples of limited choice. However, patients did not
      always feel they had the knowledge to make informed decisions. Information
      exchange was highly valued by patients when it occurred, and it increased their
      satisfaction with the process. Other factors mediating care included the use of
      the public versus private health system, the quality of information exchange (GP
      to specialist and GP to patient), continuity of care between GP and specialist,
      and the extent of information provision when patients moved between specialist
      and GP care. CONCLUSIONS: Patients described poor GP continuity, ad hoc
      organisational systems and limited information exchange, at both interpersonal
      and inter-organisational levels, all leading to sub-optimal care. Implementation
      of a system of information feedback to GPs and engagement with them might improve
      information exchange for patients, enabling them to be more involved in improved
      referral outcomes.

PMID- 23972117
TI  - A Neural Network Model of Cortical Activity during Reaching.
AB  - Abstract A neural network model that produces many of the directional and spatial
      response properties that have been observed for cortical neurons in monkeys
      moving toward targets in space is described. These include motor cortex units
      with broad tuning in a single preferred direction, approximately linear variation
      in activity for different hold positions, and approximate invariance in preferred
      direction for different starting points in space. Association cortex units in the
      model are sometimes irregular and reminiscent of neurons observed in visually
      responsive brain areas such as the posterior parietal cortex. The model is also
      compatible with population analyses performed on motor cortical neurons. Across
      network units, the distribution of preferred directions is uniformly distributed
      in directional space, and the degree of tuning and response magnitude vary from
      unit to unit. A population code used to predict accurately the direction of arm
      movements from a large population of coarsely tuned individual neurons allows
      predictions using a simulated population of unit responses obtained from the
      neural network model. This code works for different starting locations in space
      using the same parameters. 

PMID- 23972118
TI  - The processing nature of the n400: evidence from masked priming.
AB  - Abstract The N400 is an endogenous event-related brain potential (ERP) that is
      sensitive to semantic processes during language comprehension. The general
      question we address in this paper is which aspects of the comprehension process
      are manifest in the N400. The focus is on the sensitivity of the N400 to the
      automatic process of lexical access, or to the controlled process of lexical
      integration. The former process is the reflex-like and effortless behavior of
      computing a form representation of the linguistic signal, and of mapping this
      representation onto corresponding entries in the mental lexicon. The latter
      process concerns the integration of a spoken or written word into a higher-order
      meaning representation of the context within which it occurs. ERPs and reaction
      times (RTs) were acquired to target words preceded by semantically related and
      unrelated prime words. The semantic relationship between a prime and its target
      has been shown to modulate the amplitude of the N400 to the target. This
      modulation can arise from lexical access processes, reflecting the automatic
      spread of activation between words related in meaning in the mental lexicon.
      Alternatively, the N400 effect can arise from lexical integration processes,
      reflecting the relative ease of meaning integration between the prime and the
      target. To assess the impact of automatic lexical access processes on the N400,
      we compared the effect of masked and unmasked presentations of a prime on the
      N400 to a following target. Masking prevents perceptual identification, and as
      such it is claimed to rule out effects from controlled processes. It therefore
      enables a stringent test of the possible impact of automatic lexical access
      processes on the N400. The RT study showed a significant semantic priming effect
      under both unmasked and masked presentations of the prime. The result for masked
      priming reflects the effect of automatic spreading of activation during the
      lexical access process. The ERP study showed a significant N400 effect for the
      unmasked presentation condition, but no such effect for the masked presentation
      condition. This indicates that the N400 is not a manifestation of lexical access
      processes, but reflects aspects of semantic integration processes. 

PMID- 23972119
TI  - Differential effects of semantic and identity priming in patients with left and
      right hemisphere lesions.
AB  - Abstract Patients with single brain lesions in the anterior or posterior left and
      right hemispheres and a group of controls were studied in two priming
      experiments. The first experiment employed associative pairs (DOCTOR-NURSE) and
      the second employed identical pairs (NURSE-nurse). Short and long prime-target
      stimulus onset asynchronies (SOAs) (i.e., 250 and 1850 msec) were manipulated
      within block in both experiments. In the first experiment, patients with left
      hemisphere injury showed a deficient priming effect while patients with right
      hemisphere injury and controls showed a normal pattern. In contrast, all groups
      showed an identity priming effect in the second experiment. These results
      indicate that while entries in the mental lexicon are available for the groups of
      patients studied, the spread of activation to related concepts in this lexicon is
      disrupted in the left hemisphere-damaged group. 

PMID- 23972120
TI  - Distributed representation of limb motor programs in arrays of adjustable pattern
      generators.
AB  - Abstract This paper describes the current state of our exploration of how motor
      program concepts may be related to neural mechanisms. We have proposed a model of
      sensorimotor networks with architectures inspired by the anatomy and physiology
      of the cerebellum and its interconnections with the red nucleus and the motor
      cortex. We proposed the concept of rubrocerebellar and corticocerebellar
      information processing modules that function as adjustable pattern generators
      (APGs) capable of the storage, recall, and execution of motor programs. The APG
      array model described in this paper extends the single APG model of Houk et al.
      (1990) to an array of APGs whose collective activity controls movement of a
      simple two degree-of-freedom simulated limb. Our objective was to examine the APG
      array theory in a simple computational framework with a plausible relationship to
      anatomy and physiology. Results of simulation experiments show that the APG array
      model is capable of learning how to control movement of the simulated limb by
      adjusting distributed motor programs. Although the model is based on many
      simplifying assumptions, and the simulated motor control task is much simpler
      than an actual reaching task, these results suggest that the APG array model may
      provide a useful step toward a more comprehensive understanding of how neural
      mechanisms may generate motor programs. 

PMID- 23972121
TI  - The covert learning of affective valence does not require structures in
      hippocampal system or amygdala.
AB  - Abstract Following bilateral damage to the entire medial temporal lobe and
      interconnected cortices in the anterior temporal and medial frontal regions,
      patient Boswell developed a severe learning defect for all types and levels of
      Factual knowledge, including faces. In the experiments described here, however,
      we demonstrate that Boswell can acquire a non conscious bond between entirely new
      persons and the affective valence they display. The finding is important on the
      followng accounts. First, Boswell's lesions guarantee that the entorhinal and
      perirhinal cortices, hippocampus, amygdala, and higher-order neocortices in the
      anterior temporal region are not required to support this form of covert
      learning. Second, this demonstration is possible only in a patient such as
      Boswell, because in individuals with normal or only partially impaired factual
      learning, fact memory will contaminate the performance. 

PMID- 23972122
TI  - Perseverative and semantic influences on visual object naming errors in optic
      aphasia: a connectionist account.
AB  - Abstract Although perseveration-the inappropriate repetition of previous
      responses-is quite common among patients with neurological damage, relatively few
      detailed computational accounts of its various forms have been put forth. A
      particularly well-documented variety involves the pattern of errors made by
      "optic aphasic" patients, who have a selective deficit in naming visually
      presented objects. Based on our previous work in modeling impaired reading via
      meaning in deep dyslexia, we develop a connectionist simulation of visual object
      naming. The major extension in the present work is the incorporation of short
      term correlational weights that bias the network towards reproducing patterns of
      activity that have occurred on recently preceding trials. Under damage, the
      network replicates the complex semantic and perseverative effects found in the
      optic aphasic error pattern. Further analysis reveals that the perseverative
      effects are strongest when the lesions are near or within semantics, and are
      relatively mild when the preceding object evokes no response. Like optic
      aphasics, the network produces predominantly semantic rather than visual errors
      because, in contrast to reading, there is some structure in the mapping from
      visual to semantic representations for objects. Viewed together with the dyslexia
      simulations, the replication of complex empirical phenomena concerning impaired
      visual comprehension based on a small set of general connectionist principles
      strongly suggests that these principles provide important insights into the
      nature of semantic processing of visual information and its breakdown following
      brain damage. 

PMID- 23972123
TI  - A spurious category-specific visual agnosia for living things in normal human and
      nonhuman primates.
AB  - Abstract Patients with visual associative agnosia have a particular difficulty in
      identifying visually presented living things (plants and animals) as opposed to
      nonliving things. It has been claimed that this effect cannot be explained by
      differences in the inherent visual discriminability of living and nonliving
      things. To test this claim further, we performed two experiments with normal
      subjects. In Experiment 1 normal human observers were asked to identify objects
      in tachistoscopically presented line drawings. They made more errors with living
      things than with nonliving things. In Experiment 2 normal monkeys learned to
      discriminate among the same line drawings for food reward. They made many more
      errors in discriminating among living things than nonliving things. Agnosic
      patients' responses to the same line drawings were made available to us for
      correlative analysis with the subjects' responses to these drawings in
      Experiments 1 and 2. We conclude that a category-specific visual agnosia for
      living things can arise as a consequence of a modality-specific but not category
      specific impairment in visual representation, since living things are more
      similar to each other visually than nonliving things are. 

PMID- 23972124
TI  - A 19-year-old man with sickle cell disease presenting with spinal infarction: a
      case report.
AB  - INTRODUCTION: Vasculopathy of the large vessels commonly occurs in sickle cell
      disease, and as a result cerebral infarction is a well characterized complication
      of this condition. However, spinal infarction appears to be rare. Spinal infarct
      is infrequent in the non-sickle cell population as well, and accounts for only
      about 1 percent of all central nervous system infarcts. CASE PRESENTATION: In the
      present work, we report the case of a 19-year-old African-American man with
      sickle cell disease who experienced an anterior spinal infarct and subsequent
      quadriplegia. He was incidentally noted to be a heterozygote for factor V Leiden.
      We also reviewed the literature and found two previous cases of spinal cord
      infarction and sickle hemoglobin. Our literature search did not demonstrate that
      heterozygocity for factor V Leiden plays an important role in spinal cord
      infarction. CONCLUSIONS: The paucity of cases associated with sickle hemoglobin
      does not allow us to postulate any particular risk factors with sickle cell
      disease that might predispose patients to spinal cord infarction. Our patient's
      case raises the question as to whether spinal cord infarction is being missed in
      individuals with sickle cell disease and neurologic symptoms.

PMID- 23972126
TI  - Use of complementary and alternative medicine for eye-related diseases and
      conditions.
AB  - AIM: To determine the prevalence, types and characteristics associated with
      complementary and alternative medicine (CAM) use to treat eye-related diseases
      and conditions. MATERIALS AND METHODS: The 2002 and 2007 National Health
      Interview Survey (NHIS) was used to identify participants, 18 years of age and
      older, who completed the Adult Alternative Health/Complementary and Alternative
      Medicine questionnaire. Characteristics for those who reported CAM use for eye
      diseases and conditions and those who did not were compared; the types of CAM and
      the eye diseases and conditions for their use were also reported. RESULTS: In
      2002, an estimated 0.1% of US adults reported using at least one of eight CAM
      therapies for eye-related problems; in 2007 the prevalence of CAM use for eye
      diseases and conditions had increased to 0.3%. In both 2002 and 2007, those who
      reported CAM use for eye diseases and conditions were more likely to be older,
      female, white and married. In both 2002 and 2007, the most common types of CAM
      therapies used were natural herbs and vitamin supplements. Macular degeneration
      was the most common condition for which CAM therapies were used. CONCLUSIONS: The
      study suggests that there is a small and perhaps increasing proportion of the US
      population that uses CAM for eye diseases and conditions. Further research is
      needed to determine the use and effectiveness of CAM for ophthalmologic purposes.

PMID- 23972125
TI  - Gastro-oesophageal reflux disease in type 2 diabetics: symptom load and
      pathophysiologic aspects - a retro-pro study.
AB  - BACKGROUND: Information about gastro-oesophageal reflux disease (GERD) in
      patients with Diabetes mellitus type 2 (T2D) is scarce, although the incidence of
      both disorders is increasing. METHODS: This "retro-pro" study compared 65 T2D
      patients to a control group of 130 age- and sex-matched non-diabetics. GERD was
      confirmed by gastroscopy, manometry, pH-metry and barium swallow. RESULTS: In
      patients with T2D compared to controls, dysphagia (32.3% vs. 13.1%; p = 0.001)
      and globus sensation (27.7% vs. 13.8%; p = 0.021) were found more frequently,
      whereas heartburn (76.9% vs. 88.5%; p = 0.046) and regurgitation (47.7% vs.
      72.3%; p= 0.001) were predominant in non-diabetics. Despite higher body mass
      indices (31.1 +/- 5.2 vs. 27.7 +/- 3.7 kg/m2; p < 0.001), hiatal hernia was less
      frequent in T2D patients compared to controls (60.0% vs. 90.8%, p < 0.001). Lower
      oesophageal sphincter (LES) pressure was higher in patients with T2D (median 10.0
      vs. 7.2 mmHg, p = 0.016). DeMeester scores did not differ between the groups.
      Helicobacter pylori infections were more common in T2D patients (26.2% vs. 7.7%,
      p = 0.001). Barrett metaplasia (21.5% vs. 17.7%), as well as low- (10.8% vs.
      3.8%) and high-grade dysplasia (1.5% vs. 0%) were predominant in T2D patients.
      CONCLUSIONS: T2D patients exhibit different GERD symptoms, higher LES pressures
      and a decreased prevalence of hiatal hernia than non-diabetics, which may be
      related to worse oesophageal motility and, thus, a more functional rather than
      anatomical cause of GERD. Low-grade dysplasia was more than twice as high in T2D
      than in non-diabetics patients. TRIAL REGISTRATION: Ethics committee of the
      Medical University of Vienna, IRB number 720/2011.

PMID- 23972129
TI  - Quality in emergency medicine: progress to date, challenges to come.

PMID- 23972128
TI  - Definition of compartment-based radical surgery in uterine cancer: radical
      hysterectomy in cervical cancer as 'total mesometrial resection (TMMR)' by M
      Hockel translated to robotic surgery (rTMMR).
AB  - BACKGROUND: Radical hysterectomy has been developed as a standard treatment in
      Stage I and II cervical cancers with and without adjuvant therapy. However, there
      have been several attempts to standardize the technique of radical hysterectomy
      required for different tumor extension with variable success. Total mesometrial
      resection as ontogenetic compartment-based oncologic surgery - developed by open
      surgery - can be standardized identically for all patients with locally defined
      tumors. It appears to be promising for patients in terms of radicalness as well
      as complication rates. Robotic surgery may additionally reduce morbidity compared
      to open surgery. We describe robotically assisted total mesometrial resection
      (rTMMR) step by step in cervical cancer and present feasibility data from 26
      patients. METHODS: Patients (n = 26) with the diagnosis of cervical cancer were
      included. Patients were treated by robotic total mesometrial resection (rTMMR)
      and pelvic or pelvic/periaortic robotic therapeutic lymphadenectomy (rtLNE) for
      FIGO stage IA-IIB cervical cancer. RESULTS: No transition to open surgery was
      necessary. No intraoperative complications were noted. The postoperative
      complication rate was 23%. Within follow-up time (mean: 18 months) we noted one
      distant but no locoregional recurrence of cervical cancer. There were no deaths
      from cervical cancer during the observation period. CONCLUSIONS: We conclude that
      rTMMR and rtLNE is a feasible and safe technique for the treatment of compartment
      defined cervical cancer.

PMID- 23972127
TI  - Interfering with UDP-GlcNAc metabolism and heparan sulfate expression using a
      sugar analogue reduces angiogenesis.
AB  - Heparan sulfate (HS), a long linear polysaccharide, is implicated in various
      steps of tumorigenesis, including angiogenesis. We successfully interfered with
      HS biosynthesis using a peracetylated 4-deoxy analogue of the HS constituent
      GlcNAc and studied the compound's metabolic fate and its effect on angiogenesis.
      The 4-deoxy analogue was activated intracellularly into UDP-4-deoxy-GlcNAc, and
      HS expression was inhibited up to ~96% (IC50 = 16 MUM). HS chain size was
      reduced, without detectable incorporation of the 4-deoxy analogue, likely due to
      reduced levels of UDP-GlcNAc and/or inhibition of glycosyltransferase activity.
      Comprehensive gene expression analysis revealed reduced expression of genes
      regulated by HS binding growth factors such as FGF-2 and VEGF. Cellular binding
      and signaling of these angiogenic factors was inhibited. Microinjection in
      zebrafish embryos strongly reduced HS biosynthesis, and angiogenesis was
      inhibited in both zebrafish and chicken model systems. All of these data identify
      4-deoxy-GlcNAc as a potent inhibitor of HS synthesis, which hampers pro
      angiogenic signaling and neo-vessel formation. 

PMID- 23972131
TI  - Utility of computed tomography and derivation and validation of a score to
      identify an emergent outcome in 2,315 patients with suspected urinary tract
      stone.
AB  - OBJECTIVE: Because a majority of urinary tract stones (UTSs) pass spontaneously
      and clinically significant alternative pathology is rare, we hypothesize that
      many computed tomographic (CT) scans to diagnose them are likely unnecessary. We
      sought to measure the impact of renal CT scans on resource use and to justify a
      prospective study to derive a score that predicts an emergent diagnosis in
      patients with suspected UTS by doing so in our retrospective series. METHODS: We
      conducted a retrospective study of ED patients who had noncontrast CT of the
      abdomen for suspected UTS. A split-sample was used to derive and validate a score
      to predict the presence of an emergent diagnosis on CT. RESULTS: Of the 2,315
      patients (50.8% female, mean age 45 years), 49 (2.1%) had an emergent outcome
      observed on CT. An additional 12 (0.5%) patients had an urgent outcome and 239
      (10.6%) had a urologic procedure within 8 weeks of the CT. Serum white blood cell
      count, highest temperature, urine red blood cell count, and the presence of
      abdominal pain were significant predictors of the primary outcome. A score
      derived using these predictors had a potential range of -2 (0.26% predicted risk,
      0.5% actual risk of the outcome) to 6 (52% predicted risk). The score was
      moderately discriminatory with c-statistics of 0.752 (derivation) and 0.668
      (validation) and accurate with Hosmer-Lemeshow statistics of 10.553 (p  =  0.228,
      derivation) and 9.70 (p  =  0.286, validation). CONCLUSIONS: A sensible, relevant
      score derived and validated on all patients presenting with symptoms suggestive
      of renal colic could be useful in reducing abdominal CT scan ordering.

PMID- 23972132
TI  - Cardiopulmonary resuscitation and automatic external defibrillator training in
      schools: "is anyone learning how to save a life?".
AB  - OBJECTIVES: Bystander resuscitation efforts, such as cardiopulmonary
      resuscitation (CPR) and use of an automatic external defibrillator (AED), save
      lives in cardiac arrest cases. School training in CPR and AED use may increase
      the currently low community rates of bystander resuscitation. The study objective
      was to determine the rates of CPR and AED training in Toronto secondary schools
      and to identify barriers to training and training techniques. METHODS: This
      prospective study consisted of telephone interviews conducted with key school
      staff knowledgeable about CPR and AED teaching. An encrypted Web-based tool with
      prespecified variables and built-in logic was employed to standardize data
      collection. RESULTS: Of 268 schools contacted, 93% were available for interview
      and 83% consented to participate. Students and staff were trained in CPR in 51%
      and 80% of schools, respectively. Private schools had the lowest training rate
      (39%). Six percent of schools provided AED training to students and 47% provided
      AED training to staff. Forty-eight percent of schools had at least one AED
      installed, but 25% were unaware if their AED was registered with emergency
      services dispatch. Cost (17%), perceived need (11%), and school population size
      (10%) were common barriers to student training. Frequently employed training
      techniques were interactive (32%), didactic instruction (30%) and printed
      material (16%). CONCLUSIONS: CPR training rates for staff and students were
      moderate overall and lowest in private schools, whereas training rates in AED use
      were poor in all schools. Identified barriers to training include cost and
      student population size (perceived to be too small to be cost-effective or too
      large to be implemented). Future studies should assess the application of
      convenient and cost-effective teaching alternatives not presently in use.

PMID- 23972133
TI  - Does the sedation regimen affect adverse events during procedural sedation and
      analgesia in injection drug users?
AB  - OBJECTIVES: Injection drug users (IDUs) often undergo procedural sedation and
      analgesia (PSA) as part of emergency department (ED) treatment. We compared
      adverse events (AEs) using a variety of sedation regimens. METHODS: This was a
      retrospective analysis of a PSA safety audit in two urban EDs. Consecutive self
      reported IDUs were identified, and structured data describing comorbidities,
      vital signs, sedation regimens (propofol [P], propofol-fentanyl [PF], fentanyl
      midazolam [FM], ketofol [1:1 ketamine:propofol, KF], and ketamine-propofol [KP])
      and AEs were collected. The primary outcome was the proportion of patients in
      each sedation group having an AE; the secondary outcome was the proportion of
      patients having a cardiovascular or respiratory AE. RESULTS: Data were collected
      on 276 IDUs (78 P, 82 PF, 65 FM, 25 KF, and 26 KP), and 18 patients had AEs
      (6.5%, 95% CI 4.0-10.3). The AE rates were 0.0%, 8.5%, 9.2%, 12.0%, and 7.6%,
      respectively, with propofol having a significantly lower rate (Pearson
      coefficient 14.9, p  =  0.007). The cardiovascular/respiratory AE rates were
      significantly different as well, with P, KP, and KF having the lowest rates
      (Pearson coefficient 13.3, p  =  0.01). CONCLUSIONS: For IDU PSA, the overall AE
      rate was 6.5%, and propofol appeared to have a significantly lower rate.

PMID- 23972134
TI  - Unfavourable outcome for children leaving the emergency department without being
      seen by a physician.
AB  - OBJECTIVE: To assess the prevalence of an unfavourable outcome among children
      leaving without being seen by a physician in the emergency department (ED).
      METHOD: This was a prospective cohort study conducted over a complete year in a
      pediatric tertiary care ED. A random sample of all children younger than 19 years
      of age who left without being seen by a physician was contacted by phone 4 to 6
      days following the ED visit. The primary outcome was the occurrence of an
      unfavourable outcome prospectively defined using a Delphi method among 15
      pediatric emergency physicians. An unfavourable outcome was defined as
      hospitalization, the need for an invasive procedure (intravenous or intramuscular
      medication, fracture reduction, bone casting, or surgical intervention), suicide
      attempt, or death in the 72 hours following leaving without being seen by a
      physician. As a secondary outcome, multiple potential predictors were evaluated.
      The first analysis evaluated the proportion of unfavourable outcomes among
      children who left without being seen by a physician. Then logistic regression
      identified predictors of unfavourable outcomes. RESULTS: During the study period,
      61,909 children presented to the ED, 7,592 (12%) left without being seen by a
      physician, and 1,579 were recruited. Thirty-eight (2.4%; 95% CI 1.7-3.2) patients
      fulfilled the criteria for an unfavourable outcome. On multiple logistic
      regression, chief complaints related to trauma and absence of nurse counseling
      had higher risks of unfavourable outcome. CONCLUSIONS: Approximately 2% of
      children who left without being seen by a physician at a tertiary care pediatric
      ED had an unfavourable outcome.

PMID- 23972135
TI  - Are all pulmonary embolism clinical decision rules equal?
AB  - CLINICAL QUESTION: Are four common clinical decision rules, in combination with
      normal D-dimer results, comparable in their ability to clinically exclude the
      diagnosis of pulmonary embolism? ARTICLE CHOSEN: Douma RA, Mos ICM, Erkens PMG,
      et al. Performance of 4 clinical decision rules in the diagnostic management of
      acute pulmonary embolism: a prospective cohort study. Ann Intern Med 2011;154:709
      18. OBJECTIVE: To directly compare the performance of four different clinical
      decision rules, the Wells rule, revised Geneva score, simplified Wells rule, and
      simplified revised Geneva score, in combination with D-dimer results, to exclude
      pulmonary embolism.

PMID- 23972136
TI  - How to safely extubate a patient in the emergency department: a user's guide to
      critical care.

PMID- 23972137
TI  - Management of hot tar burn using vitamin e ointment containing petroleum and
      polyoxyethylene sorbitan.
AB  - Tar burns are primarily an occupational hazard associated with the road paving or
      roofing industry. Management of tar burns requires safe and effective removal of
      solidified tar from the skin using a dissolution or emulsifying agent to prevent
      inflicting further injury and pain. We report a case of a patient with tar burns
      on 10% of his body surface area involving the lower arms bilaterally and splashes
      to the facial area. The tar was efficiently removed with Webber Vitamin E
      Ointment without toxicity, irritation, or other complications.

PMID- 23972138
TI  - Central serous retinopathy: an unusual cause of acute visual loss.
AB  - Ophthalmologic complaints represent approximately 2% of emergency department (ED)
      visits. Acute vision loss is the most serious of such presentations and requires
      prompt assessment for a treatable cause. The differential diagnosis for acute
      vision loss includes retinal detachment, macular disorders, vaso-occlusive
      disorders, temporal arteritis, neuro-ophthalmologic disorders, and functional
      disorders. We report the case of a previously healthy 33-year-old man who
      presented to the ED with acute bilateral vision loss that was ultimately
      diagnosed as central serous retinopathy (CSR), an idiopathic, self-limited
      condition that typically affects males age 20 to 50 years. This condition is not
      mentioned in standard emergency medicine textbooks or the emergency medicine
      literature, and our hope is that our report will serve to illustrate a typical
      case of CSR and help prompt emergency physicians to consider this diagnosis in
      the appropriate circumstances.

PMID- 23972139
TI  - Standing in a canoe.

PMID- 23972140
TI  - Callosal disconnection and limb-kinetic apraxia.
AB  - According to Liepmann, patients with limb-kinetic apraxia (LKA) have a loss of
      upper limb deftness-dexterity. Prior studies have revealed in right-handed
      patients that, whereas injury of the left hemisphere induces an ipsilesional LKA,
      injury to the right hemisphere does not induce an ipsilesional LKA. There are at
      least two possible means by which the left hemisphere may influence the deftness
      of the left hand, either by callosal connections or by ipsilesional corticospinal
      projections. The purpose of this study was to learn whether a patient with a
      focal lesion of the corpus callosum had a callosal disconnection LKA. This 57
      year-old right-handed man had a memory impairment, and upon brain imaging, was
      found to have a septum pellucidum cyst, which was causing mild ventricular
      obstruction to the occipital and temporal horns. He underwent an endoscopic
      assisted fenestration of the septum pellucidum. Postoperative imaging revealed a
      lesion of the mesial portion of his corpus callosum and an assessment of praxis
      revealed that he had both a limb-kinetic and ideomotor apraxia of his left but
      not his right hand. The observation that this man had a callosal disconnection
      LKA of his left hand suggests that in some people it is the left hemisphere's
      premotor or motor cortex that enables the right hemisphere's motor system to
      program deft movements of the left hand. 

PMID- 23972142
TI  - Paradise lost: older Cuban American exiles' ambiguous loss of leaving the
      homeland.
AB  - To explore the experience of leaving Cuba, 2 Cuban American emigres interviewed
      20 Cuban exiles aged 65 or older, who left Cuba between 1959 and 1971. The
      interviews were conducted in New York and New Jersey using a phenomenological
      approach (Moutsakas, 1994). Themes included feeling betrayed by the Revolution,
      the inevitability of leaving, the expectation of a temporary refuge, and longing
      for and idealizing the past. The psychological presence that participants
      expressed, along with an endless sense of loss, resonates with ambiguous loss
      theory (Boss, 2006)-themes that have yet to be explored in the literature and
      that have research and practice implications.

PMID- 23972141
TI  - Confidentiality protections versus collaborative care in the treatment of
      substance use disorders.
AB  - Practitioners in federally-assisted substance use disorder (SUD) treatment
      programs are faced with increasingly complex decisions when addressing patient
      confidentiality issues. Recent policy changes, intended to make treatment more
      available and accessible, are having an impact on delivery of SUD treatment in
      the United States. The addition of electronic health records provides opportunity
      for more rapid and comprehensive communication between patients' primary and SUD
      care providers while promoting a collaborative care environment. This shift
      toward collaborative care is complicated by the special protections that SUD
      documentation receives in SUD treatment programs, which vary depending on what
      care is provided and the setting where the patient is treated. This article
      explores the special protections for substance abuse documentation, discrepancies
      in treatment documentation, ways to deal with these issues in clinical practice,
      and the need for more knowledge about how to harmonize treatment in the SUD and
      primary care systems. 

PMID- 23972143
TI  - Anti-inflammatory and anti-nociceptive activities of two new triterpenoids from
      Adiantum capillus-veneris Linn.
AB  - Two new triterpenoids characterised as 30-normethyl fernen-22-one (capillirone,
      1) and hopan-3beta-ol (capillirol B, 2), along with two known triterpenoids, 4
      alpha-hydroxyfilican-3-one and 3-beta,4-alpha-dihydroxyfilicane, have been
      isolated from the ethanolic extract of the fronds of Adiantum capillus-veneris
      Linn. (Adiantaceae). Compounds 1 and 3 showed significant anti-inflammatory
      activity with 33.07% (p < 0.01) and 42.30% (p < 0.001) inhibition as compared to
      indomethacin that exhibited 60.00% (p < 0.001) inhibition after 3 h in the
      carrageenan-induced hind paw oedema method. Compound 3 showed potent anti
      nociceptive activity with 42.37% inhibition as compared to indomethacin that
      showed 45.34% inhibition in the writhing test.

PMID- 23972144
TI  - Local and global reference frames for environmental spaces.
AB  - Two experiments examined how locations in environmental spaces, which cannot be
      overseen from one location, are represented in memory: by global reference
      frames, multiple local reference frames, or orientation-free representations.
      After learning an immersive virtual environment by repeatedly walking a closed
      multisegment route, participants pointed to seven previously learned targets from
      different locations. Contrary to many conceptions of survey knowledge, local
      reference frames played an important role: Participants performed better when
      their body or pointing targets were aligned with the local reference frame
      (corridor). Moreover, most participants turned their head to align it with local
      reference frames. However, indications for global reference frames were also
      found: Participants performed better when their body or current corridor was
      parallel/orthogonal to a global reference frame instead of oblique. Participants
      showing this pattern performed comparatively better. We conclude that survey
      tasks can be solved based on interconnected local reference frames. Participants
      who pointed more accurately or quickly additionally used global reference frames.

PMID- 23972145
TI  - 1H NMR relaxometry, viscometry, and PFG NMR studies of magnetic and nonmagnetic
      ionic liquids.
AB  - A study is presented of the molecular dynamics and of the viscosity in pure
      [Aliquat][Cl] ionic liquid and in a mixture of [Aliquat][Cl] with 1% (v/v) of
      [Aliquat][FeCl4]. The (1)H spin-lattice relaxation rate, R1, was measured by NMR
      relaxometry between 8 and 300 MHz. In addition, the translation self-diffusion,
      D, was measured by pulse field gradient NMR. The ILs' viscosity was measured as a
      function of an applied magnetic field, B, and it was found that the IL mixture's
      viscosity decreased with increasing B, whereas the [Aliquat][Cl] viscosity is
      independent of B. All experimental results were analyzed taking into account the
      viscosity's magnetic field dependence, assuming a modified Stokes-Einstein
      diffusion/viscosity relation. The main difference between the relaxation
      mechanisms responsible for R1 in the two IL systems is related to the additional
      paramagnetic relaxation contribution associated with the (1)H spins-[FeCl4]
      paramagnetic moments' interactions. Cross-relaxation cusps in the R1 dispersion,
      associated with (35)Cl and (1)H nuclear spins in the IL systems, were detected.
      The R1 model considered was successfully fitted to the experimental results, and
      it was possible to estimate the value of D at zero field in the case of the IL
      mixture which was consistent with the values of D measured at 7 and 14.1 T and
      with the magnetic field dependence estimated from the viscosity measurements. It
      was observed that a small concentration of [Aliquat][FeCl4] in the [Aliquat][Cl]
      was enough to produce a "superparamagnetic"-like effect and to change the IL
      mixture's molecular dynamics and viscosity and to allow for their control with an
      external magnetic field. 

PMID- 23972147
TI  - DNA G-quadruplex binders: a patent review.
AB  - INTRODUCTION: DNA G-quadruplexes are four-stranded DNA structures and are widely
      distributed in functional regions of the human genome, such as telomeres and gene
      promoter regions. G-quadruplex structures can play important roles, including in
      immunoglobulin gene rearrangements, DNA replication, gene transcription, and are
      viewed as valid therapeutic targets in human cancer diseases. Design of G
      quadruplex binders that target these structures and regulate related gene
      functions through stabilization of these structures are emerging as an exciting
      new class of potential anticancer agents. Besides as drug candidate, DNA G
      quadruplex binders can also serve as excellent probes, helping the further
      exploration of biological functions of G-quadruplex and early diagnosis of G
      quadruplex-related disease. AREAS COVERED: This review provides an overview of
      current knowledge on patents of DNA G-quadruplex binders from 2008 to 2013.
      Information is collected from an extensive search, covering Derwent Innovations
      Index, Espacenet, SciFinder, and Google patent search. EXPERT OPINION: With the
      accumulating evidence of G-quadruplex as an effective drug target, an increasing
      number of DNA G-quadruplex binders with diverse structural features were
      developed. These binders are either used as drug candidates targeting G
      quadruplex, or as probes for diagnostic purpose in genomic study. This review
      would mainly focus on the patents published after 2008 (including 2008). In order
      to cover all the diverse structural types of DNA G-quadruplex binders, some
      patents published before 2008 would be mentioned as well.

PMID- 23972146
TI  - Heritability of chronic obstructive pulmonary disease and related phenotypes in
      smokers.
AB  - RATIONALE: Previous studies of chronic obstructive pulmonary disease (COPD) have
      suggested that genetic factors play an important role in the development of
      disease. However, single-nucleotide polymorphisms that are associated with COPD
      in genome-wide association studies have been shown to account for only a small
      percentage of the genetic variance in phenotypes of COPD, such as spirometry and
      imaging variables. These phenotypes are highly predictive of disease, and family
      studies have shown that spirometric phenotypes are heritable. OBJECTIVES: To
      assess the heritability and coheritability of four major COPD-related phenotypes
      (measurements of FEV1, FEV1/FVC, percent emphysema, and percent gas trapping),
      and COPD affection status in smokers of non-Hispanic white and African American
      descent using a population design. METHODS: Single-nucleotide polymorphisms from
      genome-wide association studies chips were used to calculate the relatedness of
      pairs of individuals and a mixed model was adopted to estimate genetic variance
      and covariance. MEASUREMENTS AND MAIN RESULTS: In the non-Hispanic whites,
      estimated heritabilities of FEV1 and FEV1/FVC were both about 37%, consistent
      with estimates in the literature from family-based studies. For chest computed
      tomography scan phenotypes, estimated heritabilities were both close to 25%.
      Heritability of COPD affection status was estimated as 37.7% in both populations.
      CONCLUSIONS: This study suggests that a large portion of the genetic risk of COPD
      is yet to be discovered and gives rationale for additional genetic studies of
      COPD. The estimates of coheritability (genetic covariance) for pairs of the
      phenotypes suggest considerable overlap of causal genetic loci.

PMID- 23972148
TI  - Esophageal rupture caused by explosion of an automobile tire tube: a case report.
AB  - INTRODUCTION: There have been no reports in the literature of esophageal rupture
      in adults resulting from an explosion of an automobile tire. We report the first
      case of just such an occurrence after an individual bit into a tire, causing it
      to explode in his mouth. CASE PRESENTATION: A 47-year-old Han Chinese man
      presented with massive hemorrhage in his left eye after he accidentally bit an
      automobile tire tube which burst into his mouth. He was diagnosed with esophageal
      rupture based on a chest computed tomography scan and barium swallow examination.
      Drainage of empyema (right chest), removal of thoracic esophagus, exposure of
      cervical esophagus, cardiac ligation and gastrostomy were performed respectively.
      After that, esophagogastrostomy was performed. CONCLUSIONS: Successful
      anastomosis was obtained at the neck with no postoperative complications 3 months
      after the surgery. The patient was discharged with satisfactory outcomes. We
      present this case report to bring attention to esophageal rupture in adults
      during the explosion of an automobile tire tube in the mouth.

PMID- 23972149
TI  - Image segmentation cues in motion processing: implications for modularity in
      vision.
AB  - Abstract The problem of processing visual motion is underconstrained-many
      possible real world motions are compatible with any given dynamic retinal image.
      Recent psychophysical and neurophysiological experiments have shown that the
      primate visual system's normally veridical interpretation of moving patterns is
      attained through utilization of image segmentation cues unrelated to motion per
      se. These findings challenge notions of modularity in which it is assumed that
      the processing of specific scene properties, such as motion, can be studied in
      isolation from other visual processes. We discuss the implications of these
      findings with regard to both experimental and computational approaches to the
      study of visual motion. 

PMID- 23972150
TI  - Egocentric spaw representation in early vision.
AB  - Abstract Recent physiological experiments have shown that the responses of many
      neurons in V1 and V3a are modulated by the direction of gaze. We have developed a
      neural network model of the hierarchy of maps in visual cortex to explore the
      hypothesis that visual features are encoded in egocentric (spatio-topic)
      coordinates at early stages of visual processing. Most psychophysical studies
      that have attempted to examine this question have concluded that features are
      represented in retinal coordinates, but the interpretation of these experiments
      does not preclude the type of retinospatiotopic representation that is embodied
      in our model. The model also explains why electrical stimulation experiments in
      visual cortex cannot distinguish between retinal and retinospatiotopic
      coordinates in the early stages of visual processing. Psychophysical predictions
      are made for testing the existence of retinospatiotopic representations. 

PMID- 23972151
TI  - Improved Localizadon of Cortical Activity by Combining EEG and MEG with MRI
      Cortical Surface Reconstruction: A Linear Approach.
AB  - Abstract We describe a comprehensive linear approach to the problem of imaging
      brain activity with high temporal as well as spatial resolution based on
      combining EEG and MEG data with anatomical constraints derived from MRI images.
      The "inverse problem" of estimating the distribution of dipole strengths over the
      cortical surface is highly underdetermined, even given closely spaced EEG and MEG
      recordings. We have obtained much better solutions to this problem by explicitly
      incorporating both local cortical orientation as well as spatial covariance of
      sources and sensors into our formulation. An explicit polygonal model of the
      cortical manifold is first constructed as follows: (1) slice data in three
      orthogonal planes of section (needle-shaped voxels) are combined with a linear
      deblurring technique to make a single high-resolution 3-D image (cubic voxels),
      (2) the image is recursively flood-filled to determine the topology of the gray
      white matter border, and (3) the resulting continuous surface is refined by
      relaxing it against the original 3-D gray-scale image using a deformable template
      method, which is also used to computationally flatten the cortex for easier
      viewing. The explicit solution to an error minimization formulation of an optimal
      inverse linear operator (for a particular cortical manifold, sensor placement,
      noise and prior source covariance) gives rise to a compact expression that is
      practically computable for hundreds of sensors and thousands of sources. The
      inverse solution can then be weighted for a particular (averaged) event using the
      sensor covariance for that event. Model studies suggest that we may be able to
      localize multiple cortical sources with spatial resolution as good as PET with
      this technique, while retaining a much finer grained picture of activity over
      time. 

PMID- 23972152
TI  - Plurality of viual mismatch potentials in a reptile.
AB  - Abstract Studies with auditory stimuli have established in humans that a mismatch
      potential (MMP) is elicited whenever a deviant stimulus is substituted for a
      standard stimulus in a train of monotonous standard stimuli presented at rates >
      0.25 Hz. The MMP in humans is localized in the auditory cortex and is known as
      mismatch negativily, from its polarity in scalp recordings. It is hypothesized to
      reflect the operation of sensory memory and to be a necessary component of the
      auditory orienting response. To examine the generality of MMPs we used a visual
      mismatch paradigm with pond turtles (Pseudemys scripta) while recording with
      electrode arrays (200 MUm spacing) from near surface and deep visual projection
      areas within the forebrain and optic tectum. Standard stimuli were 10-sec trains
      of diffused strobe flashes presented at rates of 1-6 Hz against backgrounds of 2
      11 lux. Deviant stimuli were brighter or dimmer flashes that followed the last
      standard flash. MMps were separated from visual evoked potentials by subtracting
      the response to the last standard flash of the train from the response to the
      same flash (bright or dim) when delivered as a deviant. Comparisons were also
      made with evoked potentials to isolated bright or dim flashes, that is, equal in
      frequency (1 per 12 sec) to the deviants but without intervening standard
      flashes. At tectal loci bright and dim deviants elicited net positivities that
      reached statistical significance in the period between 141 +/- 8 and 184 +/- 12
      msec after the deviant stimulus (mean +/- SEM). Earlier components in the tectal
      responses correlated with the intensity of the stimulus rather than its deviance.
      In the case of the bright deviants the early waves (P50-P75) were larger in
      amplitude. Forebrain recordings showed a similar although broader period of net
      positivity, associated with deviance, between 129 +/- 8 and 195 +/- 12 msec.
      Deviants, delivered as isolated flash responses evoked larger early components
      (100-140 msec). In separate experiments with cortical epipial electrodes, a
      condition somewhat more comparable to scalp recording, MMPs were similar in
      latency but had a negative polarity. Regression analyses revealed a relationship
      between the amplitude (base-to-peak) of the MMF' and the degree to which the
      standard response had declined with repeated stimulation. Rate decrement, as
      measured by the isolated (long ISI) flash response minus the last standard
      response, was a significant predictor of MMP amplitudes (r(2) = 0.37, tectum;
      r(2) = 0.31, forebrain), whereas standard response amplitudes alone were not
      (r(2) = 0.09; r(2) = 0.06). MMPs are present in nonmammals plurally, that is, at
      different levels of the visual system, at least as early as the tectum. The
      existence of subcortical MMPs caution against assigning a primary or exclusive
      role to those recorded from the cortex. 

PMID- 23972153
TI  - Attention-related modulation of sensory-evoked brain activity in a visual search
      task.
AB  - Abstract When subjects are explicitly cued to focus attention on a particular
      location in visual space, targets presented at that location have been shown to
      elicit enhanced sensory-evoked activity in recordings of event-related brain
      potentials (ERPs). The present study sought to determine if this type of sensory
      facilitation also occurs during visual search tasks in which a feature
      conjunction target must be identified, presumably by means of focal attention,
      within an array of distractor items. In this experiment, subjects were required
      to discriminate the shape of a distinctively colored target item within an array
      containing 15 distractor items, and ERPs were elicited by task-irrelevant probe
      stimuli that were presented at the location of the target item or at the location
      of a distractor item on the opposite side of the array. When the delay between
      search-array onset and probe onset was 250 msec, the sensory-evoked responses in
      the latency range 75-200 msec were larger for probes presented at the location of
      the target than for probes presented at the location of the irrelevant
      distractor. These results indicate that sensory processing is modulated in a
      spatially restricted manner during visual search, and that focusing attention on
      a feature conjunction target engages neural systems that are shared with other
      forms of visual-spatial attention. 

PMID- 23972154
TI  - Bridging the Gap: Evidence from ERPs on the Processing of Unbounded Dependencies.
AB  - Abstract Since the early days of generative grammar, the study of "unbounded
      dependencies" such as wh-questions and relative clauses has occupied a central
      place in both syntactic theory and language processing research. The problem that
      such constructions pose is as follows. In a normal wh-question, a wh-phrase is
      typically displaced to the left periphery of a clause (What did you say - to
      John?); this displaced constituent is often referred to as a "filler." The vacant
      position (indicated in the previous example by a blank line) where it would
      ordinarily occur in an "echo" question (You said what to John?) is
      correspondingly referred to as a "gap." Filler and gap are mutually dependent on
      each other since they share syntactic and semantic information essential for
      successful sentence interpretation. However, since sentence processing is a
      sequential operation, a filler cannot be assigned to its gap until some time
      after it has occurred. In other words, the filler must be held in working memory
      until such time as filler-gap assignment can take place. The intent of the
      research reported here was to examine the processing of unbounded dependencies in
      English as revealed in event-related brain potentials (ERPs). To this end,
      subjects were shown both grammatical and ungrammatical yes/no-questions (Did you
      say something to John?) and wh-questions. A number of comparisons made at various
      points in these questions showed that both the storage of a filler in working
      memory and its subsequent retrieval for filler-gap assignment were associated
      with an enhanced negativity between 300 and 500 msec poststimulus over left
      anterior sites. This effect of left anterior negativity (LAN) was independent of
      and orthogonal to the grammaticality of the eliciting condition. We show how this
      interpretation coincides with recent studies that demonstrate a correlation
      between left anterior negativity, working memory capacity, and successful
      language processing. 

PMID- 23972155
TI  - Constraints on plasticity in a connectionist model of the english past tense.
AB  - Abstract This paper investigates constraints on dissociation and plasticity in a
      connectionist model undergoing random "lesions" both prior to and during
      training. When networks were trained only on phonological encodings of stem-suhed
      pairs similar to English regular verbs (e.g., walk ? walked), long-term deficits
      (i.e., "critical period" effects) were not observed, yet there were substantive
      short-term effects of injury. When training vocabulary reflected the English-like
      competition between regular (suffixed) and irregular verbs (e.g., go ? went, hit
      ? hit), the acquisition of regular verbs became increasingly susceptible to
      injury, while the irregulars were learned quickly and were relatively impervious
      to damage. Patterns of generalization to novel forms conflicts with the
      assumption that this behavioral dissociation is indicative of selective
      impairment of the learning and generalization of the past tense rule, while the
      associative lexical-based mechanism is left intact. Instead, we propose a view of
      network performance in which the regular-irregular dissociation derives from a
      general reduction in the ability to find a single-mechanism solution when
      resolving the competition between two classes of mappings. In light of other
      models in which "regular" and "irregular" forms compete (e.g., Patterson,
      Seidenberg, & McClelland, 1989), as well as patterns of performance in normal and
      disordered English speakers (e.g., Pinker, 1991), two general implications are
      discussed: (1) critical period effects need not derive from endog-enously
      determined maturational change, but instead may in part result from learning
      history in relation to characteristics of the language to be learned (i.e.,
      entrenchment), and (2) selective dissociations can result from general damage in
      systems that are not modularized in terms of rule-based vs. associative
      mechanisms. 

PMID- 23972156
TI  - The neurobiology of sensory and language processing in language-impaired
      children.
AB  - Abstract Clinical, behavioral, and neurophysiological studies of developmental
      language impairment (LI), including reading disability (RD), have variously
      emphasized different factors that may contribute to this disorder. These include
      abnormal sensory processing within both the auditory and visual modalities and
      deficits in linguistic skills and in general cognitive abilities. In this study
      we employed the event-related brain potential (ERP) technique in a series of
      studies to probe and compare Merent aspects of functioning within the same sample
      of LI/RD children. Within the group multiple aspects of processing were affected,
      but heterogeneously across the sample. ERP components linked to processing within
      the superior temporal gyrus were abnormal in a subset of children that displayed
      abnormal performance on an auditory temporal discrimination task. An early
      component of the visual ERP was reduced in amplitude in the group as a whole. The
      relevance of this effect to current conceptions of substreams within the visual
      system is discussed. During a sentence processing task abnormal hemispheric
      specialization was observed in a subset of children who scored poorly on tests of
      grammar. By contrast the group as a whole displayed abnormally large responses to
      words requiring contextual integration. The results imply that multiple factors
      can contribute to the profile of language impairment and that different and
      specific deficits occur heterogeneously across populations of LI/RD children. 

PMID- 23972157
TI  - An assessment of the semantic network in patients with Alzheimer's disease.
AB  - Abstract The present study employed multidimensional scaling and ADDTREE
      clustering analyses to derive the cognitive maps and clustering representations
      of normal elderly controls (NC), patients with Alzheimer's disease (AD), and
      patients with Hun-tington's disease (HD); the analyses were performed on
      subjects' responses in a category fluency task that involved generating animal
      names for 60 sec. A measure of the proximity of animal names was used as an index
      of associational strength; MDS and ADDTREE estimates were based on this measure.
      A comparison of the NC, AD, and HD subjects' cognitive maps suggests that the
      semantic network of AD patients is abnormal in two ways. First, the organization
      of the semantic network is disrupted. Second, new abnormal associations and
      clusterings are formed. These results support the notion that AD is characterized
      by a breakdown in the structure of semantic knowledge and not primarily by a
      deficiency in the accessibility of semantic information. 

PMID- 23972158
TI  - Role of nanoparticle geometry in endocytosis: laying down to stand up.
AB  - Nanoparticles (NPs) hold great promises for targeted disease diagnosis and
      therapy. Despite considerable progress in biomimetic design of NP-bioconjugates,
      the roles of NP size and shape in endocytosis are still not fully understood.
      Using an efficient coarse-grained molecular dynamics (CGMD) model, we simulate
      receptor-mediated endocytosis of NPs of various sizes and shapes. Our simulations
      demonstrate that both NP size and shape modulate the kinetics of endocytosis. For
      spherical NPs, there exists an optimal size at which endocytosis takes the
      shortest time. For a spherocylindrical NP with the initial upright docking
      position on the membrane plane, endocytosis proceeds through a laying-down-then
      standing-up sequence. A free energy analysis reveals that NP size primarily
      determines whether endocytosis can complete, while NP shape breaks the symmetry
      of curvature energy landscape and hence dictates the endocytic pathway and the
      angle of entry. The findings shed light on the rational design of NP-based
      diagnostic and therapeutic agents with improved cellular targeting. 

PMID- 23972159
TI  - Cash transfers for HIV prevention: considering their potential.
AB  - INTRODUCTION: Cash payments to vulnerable households and/or individuals have
      increasingly garnered attention as a means to reduce poverty, improve health and
      achieve other development-related outcomes. Recent evidence from Malawi and
      Tanzania suggests that cash transfers can impact HIV-related behaviours and
      outcomes and, therefore, could serve as an important addition to HIV prevention
      efforts. DISCUSSION: This article reviews the current evidence on cash transfers
      for HIV prevention and suggests unresolved questions for further research. Gaps
      include (1) understanding more about the mechanisms and pathways through which
      cash transfers affect HIV-related outcomes; (2) addressing key operational
      questions, including the potential feasibility and the costs and benefits of
      different models of transfers and conditionality; and (3) evaluating and
      enhancing the wider impacts of cash transfers on health and development.
      CONCLUSIONS: Ongoing and future studies should build on current findings to
      unpack unresolved questions and to collect additional evidence on the multiple
      impacts of transfers in different settings. Furthermore, in order to address
      questions on sustainability, cash transfer programmes need to be integrated with
      other sectors and programmes that address structural factors such as education
      and programming to promote gender equality and address HIV.

PMID- 23972160
TI  - Diagnosis and subtype analysis of Blastocystis sp. in 442 patients in a hospital
      setting in the Netherlands.
AB  - BACKGROUND: Blastocystis sp. are among the most commonly observed intestinal
      parasites in routine clinical parasitology. Blastocystis in humans consists of at
      least 9 genetic subtypes. Different subtypes of Blastocystis may be associated
      with differences in pathogenicity and symptomatology. METHODS: Advanced
      microscopy on two samples and sequence-confirmed PCR on a third sample from the
      same individual were used for Blastocystis diagnosis and subtype analyses on
      routine clinical samples in a university hospital. RESULTS: With a combined gold
      standard of sequence-confirmed PCR and positive advanced microscopy, 107 out of
      442 (24.2%) patients were diagnosed with Blastocystis. infection, which is a high
      frequency of detection in comparison to previous reports from industrialized
      countries. The sensitivity of microscopy and sequence-confirmed PCR was 99.1%
      (106/107) and 96.3% (103/107), respectively.Among 103 typable samples, subtype 3
      was most abundant (n = 43, 42%), followed by subtypes 1 and 2 (both n = 23, 22%),
      subtype 4 (n = 12, 12%), and single samples with subtypes 6 (1%) and subtype 7
      (1%). The prevalence of Blastocystis infection was 38% in patients from the
      Department of Tropical Medicine and 18% in patients from other departments.
      CONCLUSIONS: A high prevalence of Blastocystis infection was found with both
      advanced microscopy and sequence-confirmed PCR in our patient population. Most
      cases were caused by subtypes ST1, ST2, ST3 and ST4. A significantly higher
      prevalence was found among patients with a history of recent travel to tropical
      countries.

PMID- 23972162
TI  - Health and safety.

PMID- 23972161
TI  - Presence of autism, hyperserotonemia, and severe expressive language impairment
      in Williams-Beuren syndrome.
AB  - BACKGROUND: Deletion of the Williams-Beuren syndrome (WBS) critical region
      (WBSCR), at 7q11.23, causes a developmental disorder commonly characterized by
      hypersociability and excessive talkativeness and often considered the opposite
      behavioral phenotype to autism. Duplication of the WBSCR leads to severe delay in
      expressive language. Gene-dosage effects on language development at 7q11.23 have
      been hypothesized. METHODS: Molecular characterization of the WBSCR was performed
      by fluorescence in situ hybridization and high-resolution single-nucleotide
      polymorphism array in two individuals with severe autism enrolled in a genetic
      study of autism who showed typical WBS facial dysmorphism on systematic clinical
      genetic examination. The serotonin transporter promoter polymorphism (5-HTTLPR,
      locus SLC6A4) was genotyped. Platelet serotonin levels and urinary 6
      sulfatoxymelatonin excretion were measured. Behavioral and cognitive phenotypes
      were examined. RESULTS: The two patients had common WBSCR deletions between
      proximal and medial low copy repeat clusters, met diagnostic criteria for autism
      and displayed severe impairment in communication, including a total absence of
      expressive speech. Both patients carried the 5-HTTLPR ss genotype and exhibited
      platelet hyperserotonemia and low melatonin production. CONCLUSIONS: Our
      observations indicate that behaviors and neurochemical phenotypes typically
      associated with autism can occur in patients with common WBSCR deletions. The
      results raise intriguing questions about phenotypic heterogeneity in WBS and
      regarding genetic and/or environmental factors interacting with specific genes at
      7q11.23 sensitive to dosage alterations that can influence the development of
      social communication skills. Thus, the influence of WBSCR genes on social
      communication expression might be dramatically modified by other genes, such as 5
      HTTLPR, known to influence the severity of social communication impairments in
      autism, or by environmental factors, such as hyperserotonemia, given that
      hyperserotonemia is found in WBS associated with autism but not in WBS without
      autism. In this regard, WBS provides a potentially fruitful model with which to
      develop integrated genetic, cognitive, behavioral and neurochemical approaches to
      study genotype-phenotype correlations, possible gene-environment interactions and
      genetic background effects. The results underscore the importance of considering
      careful clinical and molecular genetic examination of individuals diagnosed with
      autism.

PMID- 23972163
TI  - Alcohol control strategies: the gap between evidence and practice.

PMID- 23972164
TI  - Monitoring patient safety in general practice: the increasing role of GPs.

PMID- 23972165
TI  - Breaking boundaries: reinventing general practice for the 21st century.

PMID- 23972166
TI  - Hard chairs.

PMID- 23972167
TI  - How much do trainers know about the CSA exam?

PMID- 23972168
TI  - Should we charge for A&E?

PMID- 23972169
TI  - Quality assurance of appraisal summaries.

PMID- 23972170
TI  - Measles targets and herd immunity.

PMID- 23972171
TI  - The Wow test in quality.

PMID- 23972173
TI  - Are we overusing thyroid function tests?

PMID- 23972174
TI  - Reducing inappropriate ENT referrals.

PMID- 23972175
TI  - The pain of pregabalin prescribing in prisons.

PMID- 23972176
TI  - Use of PHQ-9 scores to guide treatment decisions in primary care.

PMID- 23972177
TI  - Embracing the future of medical journals.

PMID- 23972178
TI  - Smoking cessation research: valuable lessons for GP trainees.

PMID- 23972179
TI  - Five biases of new technologies.

PMID- 23972180
TI  - Royal College of General Practitioners Research Paper of the Year 2012.

PMID- 23972181
TI  - Karen Viagra: Burma's best kept secret.

PMID- 23972184
TI  - Stop penalising UK GPs returning from abroad.

PMID- 23972185
TI  - The postcode lottery of GP training: Time Out of Programme.

PMID- 23972188
TI  - H is for human rights.

PMID- 23972189
TI  - Tick. Tick. Tick ....

PMID- 23972190
TI  - Inaugural Ann McPherson lecture: young people's health today--the inconvenient
      truths for primary care.

PMID- 23972191
TI  - Diagnosis and management of headaches in young people and adults: NICE guideline.

PMID- 23972192
TI  - Acceptability of screening for early detection of liver disease in
      hazardous/harmful drinkers in primary care.
AB  - BACKGROUND: It is estimated that one-quarter of adults in the UK drink at
      harmful/hazardous levels leading to increased mortality and alcohol liver disease
      (ALD). The Alcohol Liver Disease Detection Study (ALDDeS) aimed to test out in
      primary care the feasibility of alcohol misuse screening in adults, using the
      AUDIT questionnaire, and to assess screening harmful/hazardous alcohol users for
      ALD using newer non-invasive serum markers of fibrosis. AIM: To explore patients'
      experiences of taking part in ALDDeS and understanding of the delivery and
      process of screening for ALD using self-report questionnaires and feedback of
      liver fibrosis risk using levels of non-invasive serum markers. DESIGN AND
      SETTING: A nested qualitative study based in five primary care practices in the
      UK. METHOD: From a sample of patients who were identified as drinking at
      harmful/hazardous levels, 30 participants were identified by maximum variation
      sampling for qualitative in-depth interviews. Using the principles of constant
      comparison the transcribed interviews were thematically analysed. RESULTS:
      Receiving a postal AUDIT questionnaire was viewed as acceptable by participants.
      For some completing the AUDIT increased awareness of their hazardous alcohol use
      and a positive blood test indicating liver fibrosis was a catalyst for behaviour
      change. For others, a negative blood test result provided a licence to continue
      drinking at hazardous levels. A limited understanding of safe drinking and of ALD
      was common. CONCLUSION: Educational and training needs of primary care
      professionals must be taken into account, so that patients with marker levels
      indicating low risk of fibrosis are correctly informed about the likely risks of
      continuing to drink at the same levels.

PMID- 23972193
TI  - Smoking in young women in Scotland and future burden of hospital admission and
      death: a nested cohort study.
AB  - BACKGROUND: Many women smoke, yet few longitudinal studies have examined the non
      fatal burden of smoking in women. AIM: To investigate smoking in young women, and
      hospital admission and death in Scotland; and to compare mortality risk with
      elsewhere in the UK. DESIGN AND SETTING: Nested cohort study: Royal College of
      General Practitioners' Oral Contraception Study, UK. METHOD: A total of 4121
      women categorised by smoking habits and living in Scotland at recruitment (1968
      1969) were followed until March 2009. Cox regression was used to investigate
      smoking and survival time; mortality from cancer, circulatory, or respiratory
      disease, and all other causes; and hospitalisation for any reason, and for
      specific reasons. The number and type of hospital admissions and bed-days were
      examined by smoking status. Life tables and Cox regression were used to compare
      the mortality risk of women living in Scotland with that of women living
      elsewhere. RESULTS: All-cause mortality was increased in women who smoked <15
      cigarettes daily (adjusted hazard ratio = 1.99, 95% confidence interval [CI] =
      1.74 to 2.27) and those who smoked >=15 cigarettes daily (adjusted HR = 2.81, 95%
      CI = 2.47 to 3.20). Smoking any amount increased death from cancer, circulatory,
      respiratory, and other causes. Increased risk estimates were seen in one or both
      smoking groups for hospitalisation for any cause, and for several specific
      causes. More smokers than non-smokers were admitted to hospital, for four or more
      reasons, and had a longer total stay. The median survival age among smokers was
      lower in Scotland than elsewhere. Higher adjusted hazard ratios for mortality
      were found among smokers in Scotland. CONCLUSION: This study provides a powerful
      reminder of the burden of smoking in young women. In the UK, harmful effects
      appear to be worse in smokers in Scotland.

PMID- 23972194
TI  - Adverse events recorded in English primary care: observational study using the
      General Practice Research Database.
AB  - BACKGROUND: More accurate and recent estimates of adverse events in primary care
      are necessary to assign resources for improvement of patient safety, while
      predictors must be identified to ameliorate patient risk. AIM: To determine the
      incidence of recorded iatrogenic harm in general practice and identify risk
      factors for these adverse events. DESIGN AND SETTING: Cross-sectional sample of
      74,763 patients at 457 English general practices between 1 January 1999 and 31
      December 2008, obtained from the General Practice Research Database. METHOD:
      Patient age at study entry, sex, ethnicity, deprivation, practice region,
      duration registered at practice, continuity of care, comorbidities, and health
      service use were extracted from the data. Adverse events were defined by Read
      Codes for complications of care (Chapters S, T, and U). Crude and adjusted
      analyses were performed by Poisson regression, using generalised estimating
      equations. RESULTS: The incidence was 6.0 adverse events per 1000 person-years
      (95% confidence interval [CI] = 5.74 to 6.27), equivalent to eight adverse events
      per 10,000 consultations (n = 2,540,877). After adjustment, patients aged 65-84
      years (risk ratio [RR] = 5.62, 95% CI = 4.58 to 6.91; P<0.001), with the most
      consultations (RR = 2.14, 95% CI = 1.60 to 2.86; P<0.001), five or more emergency
      admissions (RR = 2.08, 95% CI = 1.66 to 2.60; P<0.001), or the most diseases
      according to expanded diagnosis clusters (RR = 8.46, 95% CI = 5.68 to 12.6;
      P<0.001) were at greater risk of adverse events. Patients registered at their
      practice for the longest periods of time were less at risk of an adverse event
      (RR = 0.40, 95% CI = 0.35 to 0.47; P<0.001). CONCLUSION: The low incidence of
      recorded adverse events is comparable with other studies. Temporal sequencing of
      risk factors and case ascertainment would benefit from data triangulation. Future
      studies may explore whether first adverse events predict future incidents.

PMID- 23972195
TI  - The prevalence and nature of prescribing and monitoring errors in English general
      practice: a retrospective case note review.
AB  - BACKGROUND: Relatively little is known about prescribing errors in general
      practice, or the factors associated with error. AIM: To determine the prevalence
      and nature of prescribing and monitoring errors in general practices in England.
      DESIGN AND SETTING: Retrospective case-note review of unique medication items
      prescribed over a 12-month period to a 2% random sample of patients. Fifteen
      general practices across three primary care trusts in England. METHOD: A total of
      6048 unique prescription items prescribed over the previous 12 months for 1777
      patients were examined. The data were analysed by mixed effects logistic
      regression. The main outcome measures were prevalence of prescribing and
      monitoring errors, and severity of errors, using validated definitions. RESULTS:
      Prescribing and/or monitoring errors were detected in 4.9% (296/6048) of all
      prescription items (95% confidence interval [CI] = 4.4% to 5.5%). The vast
      majority of errors were of mild to moderate severity, with 0.2% (11/6048) of
      items having a severe error. After adjusting for covariates, patient-related
      factors associated with an increased risk of prescribing and/or monitoring errors
      were: age <15 years (odds ratio [OR] = 1.87, 95% CI = 1.19 to 2.94, P = 0.006) or
      >64 years (OR = 1.68, 95% CI = 1.04 to 2.73, P = 0.035), and higher numbers of
      unique medication items prescribed (OR = 1.16, 95% CI = 1.12 to 1.19, P<0.001).
      CONCLUSION: Prescribing and monitoring errors are common in English general
      practice, although severe errors are unusual. Many factors increase the risk of
      error. Having identified the most common and important errors, and the factors
      associated with these, strategies to prevent future errors should be developed,
      based on the study findings.

PMID- 23972196
TI  - Prescription peer academic detailing to reduce inappropriate prescribing for
      older patients: a cluster randomised controlled trial.
AB  - BACKGROUND: Older patients are at particular risk for adverse drug reactions. In
      older people, interventions targeting potentially inappropriate prescriptions
      (PIPs) are considered important measures to minimise drug-related harm,
      especially in the general practice setting where most prescriptions for older
      patients are issued. AIM: To study the effects of a multifaceted educational
      intervention on GPs' PIPs for older patients. DESIGN AND SETTING: This was a
      cluster randomised, educational intervention study in Norwegian general practice.
      Pre-study data were captured from January 2005 to December 2005 and post-study
      data from June 2006 to June 2007. The educational intervention was carried out
      from January 2006 to June 2006. METHOD: Eighty continuing medical education (CME)
      groups (465 GPs) were randomised to receive the educational intervention on GPs'
      PIPs for older patients (41 CME groups; 256 GPs) or another educational
      intervention (39 CME groups; 209 GPs); these two groups acted as controls for
      each other. GPs' prescription data from before and after the intervention were
      assessed against a list of 13 explicit PIP criteria for patients aged >=70 years.
      In the CME groups, trained GPs carried out an educational programme, including an
      audit, focusing on the 13 criteria and their rationale. RESULTS: A total of 449
      GPs (96.6%) completed the study; 250 in the intervention group and 199 in the
      control group. After adjusting for baseline differences and clustering effects, a
      reduction relative to baseline of 10.3% (95% confidence interval = 5.9 to 15.0)
      PIPs per 100 patients aged >=70 years was obtained. CONCLUSION: Educational
      outreach visits with feedback and audit, using GPs as academic detailers in GPs'
      CME groups, reduced PIPs for older patients aged >=70 years in general practice.

PMID- 23972197
TI  - Mortality and morbidity after initial diagnostic excision biopsy of cutaneous
      melanoma in primary versus secondary care.
AB  - BACKGROUND: Current UK melanoma guidelines do not support the initial diagnostic
      excision biopsy of pigmented lesions in primary care, although this is standard
      in other countries such as Australia. Previous research in Northeast Scotland
      found that initial diagnostic excision biopsies in primary care that prove to be
      melanoma were no more likely to be incomplete than those performed in secondary
      care, but data on longer-term outcomes were not available. AIM: To determine
      whether initial diagnostic excision biopsy of cutaneous melanoma in primary
      versus secondary care leads to poorer survival and increased morbidity. DESIGN
      AND SETTING: Analysis of a linked dataset comprising pathological data from
      melanoma cases diagnosed in Northeast Scotland between 1991 and 2007, the General
      Registry Office (Scotland) death registry, and an NHS Scotland episode of care
      database. METHOD: Patient data from three sources were matched using the
      Community Health Index (CHI) number. Cox proportional hazards regression, with
      robust standard error estimates, was used to examine the hazard ratio (95%
      confidence interval) of key mortality and morbidity outcomes based on excision in
      primary versus secondary care. Analysis was conducted before and after adjustment
      for operator and patient-level factors, using a multilevel approach. RESULTS:
      Patients receiving their initial diagnostic excision biopsy for melanoma in
      primary versus secondary care were no more likely to be dead, or to have died of
      metastatic malignant melanoma. Patients who had their initial diagnostic excision
      biopsy for melanoma in primary care had significantly fewer subsequent hospital
      admissions and spent fewer days in hospital. CONCLUSION: These findings suggest
      that initial diagnostic excision biopsy of melanoma in primary care does not lead
      to poorer long-term outcomes.

PMID- 23972198
TI  - When is acute persistent cough in school-age children and adults whooping cough?
      A prospective case series study.
AB  - BACKGROUND: Pertussis is a vaccine modified disease in most age groups and hence
      subtle in its presentation. Current diagnostic approaches require relatively
      invasive sampling. AIM: To determine the incidence of B. pertussis infection
      among people aged 5-49 years identified in primary care with acute persistent
      cough using an oral fluid based diagnostic test. DESIGN AND SETTING: Active
      surveillance of acute persistent cough of 2 weeks duration or greater was
      established in Auckland, New Zealand from May to October 2011. The 15
      participating primary care practices provided care for a socioeconomically
      diverse population. METHOD: Recent B. pertussis infection was determined by
      measurement of IgG antibodies to pertussis toxin (PT) in an oral fluid sample. An
      IgG antibody titre to PT of >=70 arbitrary units defined recent infection.
      Participants reported symptoms at presentation and kept a cough diary. RESULTS: A
      total of 226 participants were enrolled: 70 (31%) were children (5-16 years) and
      156 (69%) were adults (17-49 years). Oral fluid samples were obtained from 225
      participants. Ten per cent (23/225) had recent B. pertussis infection including a
      larger proportion of children than adults (17% versus 7%, P = 0.003). Neither
      cough duration nor any individual symptom discriminated between those with and
      without recent B. pertussis infection. CONCLUSION: Pertussis is a frequent cause
      of acute persistent cough presenting to primary care. Clinical differentiation of
      pertussis from other causes of acute persistent cough is difficult. An oral fluid
      based diagnostic test, which is less invasive than other diagnostic approaches,
      has high acceptability in primary care.

PMID- 23972199
TI  - Coordination of care for individuals with advanced progressive conditions: a
      multi-site ethnographic and serial interview study.
AB  - BACKGROUND: Coordination of care for individuals with advanced progressive
      conditions is frequently poor. AIM: To identify how care is coordinated in
      generalist settings for individuals with advanced progressive conditions in the
      last year of life. DESIGN AND SETTING: A mixed methods study of three UK
      generalist clinical settings producing three parallel case studies: an acute
      admissions unit in a regional hospital, a large general practice, and a
      respiratory outpatient service. METHOD: Ethnographic observations in each
      setting, followed by serial interviews of patients with advanced progressive
      conditions and their family carers in the community. A spectrum of clinicians and
      healthcare workers were also interviewed. RESULTS: Ethnographic observations were
      conducted for 22 weeks. A total of 56 patients, 25 family carers and 17
      clinicians yielded 198 interviews. Very few participants had been identified for
      a palliative approach. Rapid throughput of hospital patients and time pressures
      in primary care hindered identification of palliative care needs. Lack of care
      coordination was evident during emergency admissions and discharges. Patient,
      families, and professionals identified multiple problems relating to lack of
      information, communication, and collaboration at care transitions. Family carers
      or specialist nurses, where present, usually acted as the main care coordinators.
      CONCLUSION: Care is poorly coordinated in generalist settings for patients in the
      last year of life, although those with cancer have better coordinated care than
      other patients. A model to improve coordination of care for all individuals
      approaching the end of life must ensure that patients are identified in a timely
      way, so that they can be assessed and their care planned accordingly.

PMID- 23972200
TI  - Demand management: misguided solutions?

PMID- 23972201
TI  - Sudden sensorineural hearing loss: early diagnosis improves outcome.

PMID- 23972202
TI  - Unique, polyfucosylated glycan-receptor interactions are essential for
      regeneration of Hydra magnipapillata.
AB  - Cell-cell communications, cell-matrix interactions, and cell migrations play a
      major role in regeneration. However, little is known about the molecular players
      involved in these critical events, especially cell surface molecules. Here, we
      demonstrate the role of specific glycan-receptor interactions in the regenerative
      process using Hydra magnipapillata as a model system. Global characterization of
      the N- and O-glycans expressed by H. magnipapillata using ultrasensitive mass
      spectrometry revealed mainly polyfucosylated LacdiNAc antennary structures.
      Affinity purification showed that a putative C-type lectin (accession number
      Q6SIX6) is a likely endogenous receptor for the novel polyfucosylated glycans.
      Disruption of glycan-receptor interactions led to complete shutdown of the
      regeneration machinery in live Hydra. A time-dependent, lack-of-regeneration
      phenotype observed upon incubation with exogenous fuco-lectins suggests the
      involvement of a polyfucose receptor-mediated signaling mechanism during
      regeneration. Thus, for the first time, the results presented here provide direct
      evidence for the role of polyfucosylated glycan-receptor interactions in the
      regeneration of H. magnipapillata. 

PMID- 23972203
TI  - A quantitative method for comparing human dentition with tooth marks using three
      dimensional technology and geometric morphometric analysis.
AB  - OBJECTIVE: To develop a quantitative method to compare 3D overlays from dental
      casts with experimental bitemarks by using geometric morphometric analysis.
      MATERIALS AND METHODS: Thirteen upper and lower dental casts and corresponding
      simulated bitemarks were 3D-scanned to generate comparison overlays with
      DentalPrint software((c)). This study considered the inter-canine distance and
      four incisal angles. A matrix was created to compare all possible combinations of
      matches and non-matches between models and bites, i.e. 169 combinations (13
      models * 13 bites), of which 13 were true matches. For each combination, the
      percentage difference was calculated between the variables in the model and the
      same variables in the bitemark. Logistic regression was used to obtain a
      predictive model (algorithm) for a match, calculating the discriminative values
      (area under the ROC curve, sensitivity and specificity) for each measure and for
      the logistic model. RESULTS: Statistically significant discriminative power was
      found for all single (angle or distance) and combined (logistic model) variables,
      with lower 95% CI limits > 0.50 for areas under the ROC curves and
      sensitivity/specificity values > 50% in both maxilla and mandible. CONCLUSIONS:
      This quantitative method has sufficient discriminative power to be utilized in
      forensic cases.

PMID- 23972204
TI  - Organization and overall job satisfaction among publicly employed, salaried
      dentists in Sweden and Denmark.
AB  - BACKGROUND: In Sweden and Denmark, clinical dentistry is changing and public
      dentistry is in transition towards more market orientation. Dentists' overall job
      satisfaction is important for how public dentistry can fulfil the new
      expectations from patients, the public and politicians. OBJECTIVES: The aim of
      this study was to investigate what organizational factors were important for
      publicly employed salaried dentists' overall job satisfaction. METHODS: A random
      sample of active, general dental practitioners (private and publicly employed)
      was selected in Denmark and in Sweden, and they received a postal questionnaire.
      The number of questionnaires was 1835 and the response rate was 68% (n = 1226).
      This study analysed only the publicly employed dentists. The sampling frame for
      the Swedish dentists was 431, response rate 68.9% (n = 297) and for the Danish
      ones 194, response rate 81.9% (n = 159). Multivariate regression was used with
      overall job satisfaction as a dependent variable. RESULTS: Common organizational
      variables were important. The used model explained between 32% (Sweden) and 39%
      (Denmark) of the variance in overall job satisfaction. The only significant
      individual factor was less job satisfaction for Swedish dentists born outside
      Sweden. An organizational climate characterized by a focus on professional values
      was associated with job satisfaction in both countries. Among the Swedish
      dentists, number of colleagues and degree of influence were also important and
      among the Danish ones sufficient time for patients. CONCLUSIONS: Organizational
      factors had an impact on salaried publicly employed dentists' overall job
      satisfaction in both countries. The findings may have implications for other
      Human Service Organizations with employed professionals.

PMID- 23972205
TI  - Developing and testing a street audit tool using Google Street View to measure
      environmental supportiveness for physical activity.
AB  - BACKGROUND: Walking for physical activity is associated with substantial health
      benefits for adults. Increasingly research has focused on associations between
      walking behaviours and neighbourhood environments including street
      characteristics such as pavement availability and aesthetics. Nevertheless,
      objective assessment of street-level data is challenging. This research
      investigates the reliability of a new street characteristic audit tool designed
      for use with Google Street View, and assesses levels of agreement between
      computer-based and on-site auditing. METHODS: The Forty Area STudy street VIEW
      (FASTVIEW) tool, a Google Street View based audit tool, was developed
      incorporating nine categories of street characteristics. Using the tool, desk
      based audits were conducted by trained researchers across one large UK town
      during 2011. Both inter and intra-rater reliability were assessed. On-site street
      audits were also completed to test the criterion validity of the method. All
      reliability scores were assessed by percentage agreement and the kappa statistic.
      RESULTS: Within-rater agreement was high for each category of street
      characteristic (range: 66.7%-90.0%) and good to high between raters (range: 51.3%
      89.1%). A high level of agreement was found between the Google Street View audits
      and those conducted in-person across the nine categories examined (range: 75.0%
      96.7%). CONCLUSION: The audit tool was found to provide a reliable and valid
      measure of street characteristics. The use of Google Street View to capture
      street characteristic data is recommended as an efficient method that could
      substantially increase potential for large-scale objective data collection.

PMID- 23972208
TI  - Accelerated surface-enhanced Raman spectroscopy (SERS)-based immunoassay on a
      gold-plated membrane.
AB  - A rapid and simple SERS-based immunoassay has been developed to overcome
      diffusion-limited binding kinetics that often impedes rapid analysis in
      conventional heterogeneous immunoassays. This paper describes the development of
      an antibody-modified membrane as a flow-through capture substrate for a
      nanoparticle-enabled SERS immunoassay to enhance antibody-antigen binding
      kinetics. A thin layer of gold is plated onto polycarbonate track-etched
      nanoporous membranes via electroless deposition. Capture antibody is immobilized
      onto the surface of a gold-plated membrane via thiolate coupling chemistry to
      serve as a capture substrate. A syringe is then used to actively transport the
      analyte and extrinsic Raman labels to the capture substrate. The fabrication of
      the gold-plated membrane is thoroughly investigated and established as a viable
      capture substrate for a SERS-based immunoassay in the absence of sample/SERS
      label flow. A syringe pump is used to systematically investigate the effect of
      flow rate on antibody-antigen binding kinetics and demonstrate that active
      transport to the capture membrane surface expedites antibody-antigen binding.
      Mouse IgG and goat anti-mouse IgG are selected as a model antigen-antibody system
      to establish proof of principle. It is demonstrated that the assay for mouse IgG
      is reduced from 24 h to 10 min and a 10-fold improvement in detection limit is
      achieved with the flow assay developed herein relative to the passive, i.e., no
      flow, assay. Moreover, mouse serum is directly analyzed and IgG level is
      determined using the flow assay. 

PMID- 23972210
TI  - Structural intermediates and folding events in the early assembly of the
      ribosomal small subunit.
AB  - Using all-atom explicit solvent molecular dynamics (MD) simulations, we
      investigated the early structural intermediates of the 5' domain of the 16S rRNA
      in Escherichia coli upon the removal of the primary binding r-proteins S4, S17,
      and S20 and the secondary binding r-protein S16. Removal of each r-protein
      corresponded to the disappearance of subdomains with correlated dynamics.
      Correlation-based network analysis of the MD trajectories of the naked rRNA
      showed that the different subdomains are connected via multiple pathways with
      high betweenness. These pathways cross at the internal loop of helix 17 (h17) in
      the five-way junction (5WJ). The structure of the internal loop is disrupted by
      the binding of S17 and rescued by the addition of S16, suggesting an important
      function of the secondary binding protein in biasing the rRNA folding landscape
      toward the native basin. Using structure-based Go simulations, we investigated
      the folding barriers of the lower four-way junction (4WJ) with h6, which is the
      primary binding site of S20 and the first to be transcribed. The folding of the
      4WJ is consistent with the protection patterns observed in hydroxyl radical
      footprinting. Results from the all-atom simulations show that the fluctuations in
      the 5WJ are independent of the fluctuations in the 4WJ, suggesting that the
      subdomains fold independently and are stabilized by primary r-proteins.

PMID- 23972209
TI  - Sustained-input switches for transcription factors and microRNAs are central
      building blocks of eukaryotic gene circuits.
AB  - WaRSwap is a randomization algorithm that for the first time provides a practical
      network motif discovery method for large multi-layer networks, for example those
      that include transcription factors, microRNAs, and non-regulatory protein coding
      genes. The algorithm is applicable to systems with tens of thousands of genes,
      while accounting for critical aspects of biological networks, including self
      loops, large hubs, and target rearrangements. We validate WaRSwap on a newly
      inferred regulatory network from Arabidopsis thaliana, and compare outcomes on
      published Drosophila and human networks. Specifically, sustained input switches
      are among the few over-represented circuits across this diverse set of
      eukaryotes. 

PMID- 23972212
TI  - Skeletal muscle dysfunction in idiopathic pulmonary arterial hypertension.
AB  - Despite improvements in survival with disease-targeted therapies, the majority of
      patients with pulmonary arterial hypertension (PAH) have persistent exercise
      intolerance that results from impaired cardiac function and skeletal muscle
      dysfunction. Our intent was to understand the molecular mechanisms mediating
      skeletal muscle dysfunction in PAH. A total of 12 patients with PAH and 10
      matched control subjects were assessed. Patients with PAH demonstrated diminished
      exercise capacity (lower oxygen uptake max, lower anaerobic threshold and higher
      minute ventilation/CO2) compared with control subjects. Quadriceps muscle cross
      sectional area was significantly smaller in patients with PAH. The vastus
      lateralis muscle was biopsied to enable muscle fiber morphometric assessment and
      to determine expression levels/activation of proteins regulating (1) muscle mass,
      (2) mitochondria biogenesis and shaping machinery, and (3) excitation-contraction
      coupling. Patients with PAH demonstrated a decreased type I/type II muscle fiber
      ratio, with a smaller cross-sectional area in the type I fibers. Diminished AKT
      and p70S6 kinase phosphorylation, with increased atrogin-1 and muscle RING-finger
      protein-1 transcript levels, were evident in the PAH muscle, suggesting
      engagement of cellular signaling networks stimulating ubiquitin-proteasome
      mediated proteolysis of muscle, with concurrent depression of networks mediating
      muscle hypertrophy. Although there were no differences in expression/activation
      of proteins associated with mitochondrial biogenesis or fission (MTCO2
      [cytochrome C oxidase subunit II]/succinate dehydrogenase flavoprotein subunit A,
      mitochondrial transcription factor A, nuclear respiratory factor-1/dynamin
      related protein 1 phosphorylation), protein levels of a positive regulator of
      mitochondrial fusion, Mitofusin2, were significantly lower in patients with PAH.
      Patients with PAH demonstrated increased phosphorylation of ryanodine receptor 1
      receptors, suggesting that altered sarcoplasmic reticulum Ca(++) sequestration
      may impair excitation-contraction coupling in the PAH muscle. These data suggest
      that muscle dysfunction in PAH results from a combination of muscle atrophy and
      intrinsically impaired contractility. 

PMID- 23972214
TI  - Lexical quality and eye movements: individual differences in the perceptual span
      of skilled adult readers.
AB  - Two experiments used the gaze-contingent moving-window paradigm to investigate
      whether reading comprehension and spelling ability modulate the perceptual span
      of skilled adult readers during sentence reading. Highly proficient reading and
      spelling were both associated with increased use information to the right of
      fixation, but did not systematically modulate the extraction of information to
      the left of fixation. Individuals who were high in both reading and spelling
      ability showed the greatest benefit from window sizes larger than 11 characters,
      primarily because of increases in forward saccade length. They were also
      significantly more disrupted by being denied close parafoveal information than
      those poor in reading and/or spelling. These results suggest that, in addition to
      supporting rapid lexical retrieval of fixated words, the high quality lexical
      representations indexed by the combination of high reading and spelling ability
      support efficient processing of parafoveal information and effective saccadic
      targeting.

PMID- 23972213
TI  - Geriatric palliative care: do medical students' narrative reflections after a
      hospice clinical experience link to geriatric competencies?
AB  - Since the Association of American Medical Colleges geriatric competencies were
      released, educators are striving to incorporate them into medical student
      curricula. The purpose of this study is to examine medical students' reflections
      after an interdisciplinary, hospice staff-precepted clinical experience, and
      whether these reflections relate to the geriatric competencies which focus on
      palliative care. From July 2010 to June 2011, 155 2nd- and 3rd-year medical
      students participated in a required, half-day hospice experience, with 120 (77%)
      submitting narrative reflections for analysis. The narratives were analyzed using
      the constant comparative method associated with grounded theory, followed by
      consensus-building in an iterative process, to identify themes. Six themes were
      identified from the analysis of student narratives: demonstrating a new or
      expanded knowledge of hospice care (79%, 95/120), developing new insights about
      self and others (74%, 89/120), changing attitudes toward hospice care (63%,
      76/120), linking patient needs with appropriate team members (43%, 52/120),
      understanding patient goals of care (43%, 51/120), and discussing palliative care
      as a treatment option (27%, 32/120). The authors conclude that a brief,
      interdisciplinary, hospice staff-precepted clinical experience is an effective
      model to inspire medical students to reflect on geriatric palliative care.
      Students clearly reflected on the geriatric palliative care competencies of
      symptom assessment and management, and gained insight into the role of the
      hospice team members and how hospice care can be a positive treatment option.
      Future educators should think about building on this type of high impact learning
      experience, and developing items to measure application of knowledge gained. 

PMID- 23972215
TI  - Polyketides with New Delhi metallo-beta-lactamase 1 inhibitory activity from
      Penicillium sp.
AB  - Three new polyketide compounds (1-3), a new quinolone alkaloid (4), and seven
      known polyketide derivatives were identified from the cultures of Penicillium sp.
      I09F 484, a strain isolated from the rhizosphere soil of the plant Picea asperata
      from Kanas Lake, Xinjiang, China. Their structures were elucidated by extensive
      spectroscopic data analysis. The absolute configurations of 1 and 4 were
      established by quantum chemical time-dependent density functional theory
      electronic circular dichroism calculation and Marfey's method, respectively.
      Compounds 1 and 2 displayed inhibitory activity against New Delhi metallo-beta
      lactamase 1 with IC50 values of 94.9 and 87.9 MUM, respectively.

PMID- 23972216
TI  - Total synthesis of (+)-18-epi-latrunculol A.
AB  - An enantioselective total synthesis of the cytotoxic latrunculin congener (+)-18
      epi-latrunculol A has been achieved. Key steps in the synthetic route include an
      acid-mediated enone cyclization/equilibration sequence, a Carreira alkynylation,
      and a late-stage Mitsunobu macrolactonization to construct the macrolide
      skeleton. 

PMID- 23972217
TI  - Visual Mental Imagery Activates Topographically Organized Visual Cortex: PET
      Investigations.
AB  - Abstract Cerebral blood flow was measured using positron emission tomography
      (PET) in three experiments while subjects performed mental imagery or analogous
      perceptual tasks. In Experiment 1, the subjects either visualized letters in
      grids and decided whether an X mark would have fallen on each letter if it were
      actually in the grid, or they saw letters in grids and decided whether an X mark
      fell on each letter. A region identified as part of area 17 by the Talairach and
      Tournoux (1988) atlas, in addition to other areas involved in vision, was
      activated more in the mental imagery task than in the perception task. In
      Experiment 2, the identical stimuli were presented in imagery and baseline
      conditions, but subjects were asked to form images only in the imagery condition;
      the portion of area 17 that was more active in the imagery condition of
      Experiment 1 was also more activated in imagery than in the baseline condition,
      as was part of area 18. Subjects also were tested with degraded perceptual
      stimuli, which caused visual cortex to be activated to the same degree in imagery
      and perception. In both Experiments 1 and 2, however, imagery selectively
      activated the extreme anterior part of what was identified as area 17, which is
      inconsistent with the relatively small size of the imaged stimuli. These results,
      then, suggest that imagery may have activated another region just anterior to
      area 17. In Experiment 3, subjects were instructed to close their eyes and
      evaluate visual mental images of upper case letters that were formed at a small
      size or large size. The small mental images engendered more activation in the
      posterior portion of visual cortex, and the large mental images engendered more
      activation in anterior portions of visual cortex. This finding is strong evidence
      that imagery activates topographically mapped cortex. The activated regions were
      also consistent with their being localized in area 17. Finally, additional
      results were consistent with the existence of two types of imagery, one that
      rests on allocating attention to form a pattern and one that rests on activating
      stored visual memories. 

PMID- 23972218
TI  - Preattentive processes guide visual search: evidence from patients with
      unilateral visual neglect.
AB  - Abstract Preattentive processes such as perceptual grouping are thought to be
      important in the initial guidance of visual attention and may also operate in
      unilateral neglect by contributing to the definition of a task-appropriate
      reference frame. We explored this question with a visual search task in which
      patients with unilateral visual neglect (5 with right-, 2 with left-hemisphere
      damage) searched a diamond-shaped matrix for a conjunction target that shared one
      feature with each of two distractor elements. Additional grouping stimuli
      appeared as flanks either on the left, right, or both sides of the central
      matrix, and significantly changed performance in the search task. As expected,
      when flanks appeared only on the ipsilesional side a decrement in search
      performance was observed, but the further addition of contralesional flanks
      actually reduced the decrement and returned performance to near baseline levels.
      These data suggest that flanking stimuli on the neglected contralesional side of
      visual space can influence the reference frame by grouping with task-relevant
      stimuli, and that this preattentive influence can be preserved in patients with
      unilateral visual neglect. 

PMID- 23972219
TI  - Express saccades and smooth pursuit eye movement function in schizophrenic,
      affective disorder, and normal subjects.
AB  - Abstract Saccadic and smooth pursuit eye movements were recorded in three groups
      of subjects: a schizophrenic group, a non-schizophrenic psychotic patient
      comparison group, and a normal control group. Schizophrenic subjects demonstrated
      a greater decrease in saccadic response time than did normal controls in a gap
      task (when the fixation point was turned off 150 msec before the target
      appeared). The psychiatric comparison subjects did not differ from normal
      controls. Further, only schizophrenic subjects demonstrated a relation between
      smooth pursuit and saccadic eye movement performance, such that subjects with
      impaired smooth pursuit showed a larger decrease in saccadic response time in the
      gap task. The relation between performance on the gap task and quality of smooth
      pursuit and its relevance for a prefrontal deficit hypothesis of schizophrenia
      are discussed. 

PMID- 23972220
TI  - Language acquisition and cerebral specialization in 20-month-old infants.
AB  - Abstract The purpose of the present study was to examine patterns of neural
      activity relevant to language processing in 20-month-old infants, and to
      determine whether or not changes in cerebral organization occur as a function of
      specific changes in language development. Event-related potentials (ERPs) were
      recorded as children listened to a series of words whose meaning was understood
      by the child, words whose meaning the child did not understand, and backward
      words. The results showed that specific and different ERP components
      discriminated comprehended words from unknown and from backward words. Distinct
      lateral and anterior-posterior specializations were apparent in EW responsiveness
      to the different types of words. Moreover, the results suggested that increasing
      language abilities were associated with increasing cerebral specialization for
      language processing over the temporal and parietal regions of the left
      hemisphere. 

PMID- 23972221
TI  - Dissociation of brain activity related to syntactic and semantic aspects of
      language.
AB  - Abstract In psycholinguistic research, there has been considerable interest in
      understanding the interactions of difFerent types of linguistic information
      during language processing. For example, does syntactic information interact with
      semantic or pragmatic information at an early stage of language processing, or
      only at later stages in order to resolve ambiguities of language? Developing
      reliable measures of language processes such as syntax and semantics is important
      to address many of these theoretical issues in psycholinguistics. In the present
      study, event-related brain potentials (ERPs) were recorded from healthy young
      subjects while they read pairs of words presented one word at a time. The ERPs
      for the second word of each pair were compared as a function of whether the
      preceding word was or was not (1) semantically related (i.e., synonyms; "semantic
      condition") or (2) grammatically correct ("syntactic condition"). In the semantic
      condition the ERPs obtained to words preceded by nonsemantically related words
      elicited an N400 component that was maximal over centroparietal scalp regions. In
      contrast, in the syntactic condition the ERPs obtained to words preceded by
      grammatically incorrect articles or pronouns yielded a negativity with a later
      onset, and a frontopolar, left hemisphere scalp maximum. This replicates our
      previous findings of a syntactic negativity in a word pair design that was
      performed in the German language. Further, the present data provide scalp
      distributional information, which suggests that the syntactic negativity
      represents brain processes that are dissociable from the centroparietal N400
      component. Thus, these findings provide strong evidence for a separate negative
      polarity ERP component that indexes syntactic aspects of language processing. 

PMID- 23972222
TI  - Event-related brain potentials while encountering semantic and syntactic
      constraint violations.
AB  - Abstract The objective of the present study was to delineate brain-electrical
      correlates of semantic and syntactic integration processes during language
      comprehension. Twenty-eight subjects were engaged in a lexical decision task. The
      target item (a legal word or a pseudo word) was always preceded by a prime
      consisting of a sentence fragment that provided a particular context. With
      respect to the prime a word target could be either a correct completion, a
      violation of a semantic selection restriction, or a violation of a syntactic
      subcategorization rule. An N400-like wave was elicited by both types of
      deviations. Syntactic anomalies evoked a negative shift predominantly over the
      anterior scalp with a preponderance over the left hemisphere, while semantic
      anomalies were accompanied by a much more widespread negativity with the maximum
      over posterior temporal areas. The amplitude of the semantic vie lation effect
      was found to be related to the strength of the priming constraints. The
      topographic difference is consistent with the idea that syntactic and semantic
      aspects of comprehension are handled by different neural subsystems. 

PMID- 23972223
TI  - The Human Auditory Sensory Memory Trace Persists about 10 sec: Neuromagnetic
      Evidence.
AB  - Abstract Neuromagnetic responses were recorded to frequent "standard tones of
      l000 Hz and to infrequent 1100-Hz "deviant" tones with a 24-channel planar SQUID
      gradiometer. Stimuli were presented at constant interstimulus intervals (ISIs)
      ranging from 0.75 to 12 sec. The standards evoked a prominent 100-msec response,
      N100m, which increased in amplitude with increasing ISI. N100m could be
      dissociated into two subcomponents with different source areas. The posterior
      component, N100m(2), increased when the ISI grew up to 6 sec, whereas the more
      anterior component, N100m(2), probably continued its growth beyond the 12-sec
      ISI. At ISIs from 0.75 to 9 sec, the deviants elicited additionally a mismatch
      field (MMF). The equivalent sources of both N100m and MMF were at the supra
      temporal auditory cortex. We assume that auditory stimuli leave in the auditory
      system a trace that affects the processing of the subsequent stimuli. The
      decrement of the N100m amplitude as well as elicitation of MMF can be considered
      as indirect evidence of active traces. A behavioral estimate of the persistence
      of the sensory auditory memory was obtained in a separate experiment in which the
      subject compared, without attending to the stimuli, tones presented at the
      daerent ISIs. The subjects discriminated the stimuli better than merely by chance
      at ISIs of 0.75-9 sec. The ISI dependence of the behavioral estimate as well as
      of N100m(2) and MMF are similar enough to suggest a common underlying mechanism
      that retains information for a period of about 10 sec. 

PMID- 23972225
TI  - The merging of the senses.

PMID- 23972224
TI  - Similarity of structure and the profile of visual recognition defects: a comment
      on gaffan and heywood.

PMID- 23972226
TI  - Glycopeptide antibiotic analogs efficient against vancomycin-resistant bacteria:
      a patent evaluation (WO2013022763).
AB  - The patent claims the preparation of vancomycin analogs equally active against
      bacterial strains that are primarily sensitive or resistant to this antibiotic.
      The pseudopeptide core of new compounds carries the amidine group that replaces
      the carboxamide linking group in the D ring-bearing amino acid residue of the
      glycopeptide. An elegant method of synthesis of amidine containing glycopeptides
      via thioamides was developed. The key glycopeptide thioamide analogs were
      prepared by total multistep synthesis. These analogs can be readily converted to
      the antibiotic's amidine as well as to alkylamidines, amidrazones,
      hydroxyamidines and similar analogs. The new analogs are capable of circumventing
      bacterial resistance derived from the D-Ala-D-Ala to D-Ala-D-Lac alteration - the
      mechanism operational in the resistant strains VanA and VanB. The interaction of
      the carboxamide, thioamide and amidine fragments of vancomycin analogs with the
      targets in resistant and sensitive bacteria was investigated. The novel compounds
      demonstrated potent activity against VanA-resistant bacteria Enterococcus
      faecalis (minimal inhibitory concentration = 0.3 - 0.6 MUg/ml). However data on
      susceptible strains and resistant clinical isolates are lacking to further
      document the interest of the compounds. The results provide evidence for
      structural modifications that can improve the therapeutic efficacy of vancomycin,
      in particular, for treatment of vancomycin-resistant infections.

PMID- 23972227
TI  - Pulmonary adenocarcinoma metastasis to a dorsal root ganglion: a case report and
      review of the literature.
AB  - INTRODUCTION: The dorsal root ganglion is a rare manifestation of metastatic
      spread. We report what we believe to be the first case of metastasis of a
      pulmonary adenocarcinoma to the lumbar dorsal root ganglion. Only four
      descriptions for different primary tumors spreading to the dorsal root ganglion
      have been described in the literature so far. CASE PRESENTATION: A 70-year-old
      Caucasian woman with a four-month history of left-sided lumbar radiculopathy was
      admitted to our department under the assumption of a herniated lumbar disc. Her
      past medical history included a pulmonary adenocarcinoma and invasive ductal
      breast cancer.Lumbar magnetic resonance imaging revealed a space-occupying mass
      in her left neuroforamen L3-L4 with compression of her L3 nerve root. Neurinoma
      was taken into account as a differential diagnosis, although not considered
      typical. Surgery revealed a metastasis of pulmonary adenocarcinoma to her dorsal
      root ganglion. CONCLUSIONS: Dorsal root ganglion metastases seem to be extremely
      rare and can mimic primary local nerve sheath tumors. Therefore, they usually
      present as incidental findings. Resection should be performed strictly under
      intraoperative monitoring as tumor spread between the nerve fibers is commonly
      observed. Metastases should be taken into account in spinal nerve tumors
      involving the dorsal root ganglion, especially in patients harboring known
      malignant diseases. The low incidence means that no clear treatment advice can be
      given. Resection is possible under intraoperative monitoring and relieves
      neurological symptoms.

PMID- 23972228
TI  - BeCH2: the simplest metal carbene. High levels of theory.
AB  - The simplest metal carbene, BeCH2, is experimentally unknown. Its isomer, HBeCH,
      lies higher in energy, but has been detected by the infrared matrix isolation [J.
      Am. Chem. Soc. 1998, 120, 6097]. In the present study the ground and low-lying
      excited states of the BeCH2 and HBeCH isomers were investigated using state-of
      the-art ab initio methods, including coupled-cluster theory with up to full
      quadruple excitations (CCSDTQ), and complete active space self-consistent field
      (CASSCF) with multireference configuration interaction with single and double
      excitations (MRCISD). The relative energies were obtained using the focal point
      analysis combined with large correlation-consistent cc-pCVXZ basis sets (X = D,
      T, Q, 5) and were extrapolated to the complete basis set (CBS) limit. The (3)B1
      state of BeCH2 (C(2v) symmetry) is the global minimum on the ground triplet
      potential energy surface (PES). The (3)Sigma(-) state of the linear isomer HBeCH
      is located 4.9 kcal mol(-1) above the global minimum, at the CCSDTQ/CBS level of
      theory. The BeCH2 and HBeCH isomers are connected through the (3)A" transition
      state lying 46.1 kcal mol(-1) above the global minimum. The higher-lying energy
      HBeCH structure has much larger Be-C bond dissociation energy (126.6 kcal mol(
      1), cf. BDE(BeCH2) = 62.1 kcal mol(-1)). The lowest excited state of BeCH2 is the
      open-shell (1)B1 state, with a relative energy of only 4.9 kcal mol(-1) above the
      global minimum, followed by (1)A1 state (16.8 kcal mol(-1)) at the MRCISD/cc
      pCVQZ level of theory. For the HBeCH isomer the lowest-energy excited states are
      (1)Delta and (1)Sigma(+), lying about 30 kcal mol(-1) above the global minimum.
      For the ground state of BeCH2 the fundamental vibrational frequencies computed
      using second-order vibrational perturbation theory (VPT2) at the CCSD(T)/cc-pCVQZ
      level are reported. We hope that our highly accurate theoretical results will
      assist in the experimental identification of BeCH2.

PMID- 23972229
TI  - Diversity and relationships in key traits for functional and apparent quality in
      a collection of eggplant: fruit phenolics content, antioxidant activity,
      polyphenol oxidase activity, and browning.
AB  - Eggplant (Solanum melongena) varieties with increased levels of phenolics in the
      fruit present enhanced functional quality, but may display greater fruit flesh
      browning. We evaluated 18 eggplant accessions for fruit total phenolics content,
      chlorogenic acid content, DPPH scavenging activity, polyphenol oxidase (PPO)
      activity, liquid extract browning, and fruit flesh browning. For all the traits
      we found a high diversity, with differences among accessions of up to 3.36-fold
      for fruit flesh browning. Variation in total content in phenolics and in
      chlorogenic acid content accounted only for 18.9% and 6.0% in the variation in
      fruit flesh browning, and PPO activity was not significantly correlated with
      fruit flesh browning. Liquid extract browning was highly correlated with
      chlorogenic acid content (r = 0.852). Principal components analysis (PCA)
      identified four groups of accessions with different profiles for the traits
      studied. Results suggest that it is possible to develop new eggplant varieties
      with improved functional and apparent quality. 

PMID- 23972230
TI  - Positioning medical students for the geriatric imperative: using geriatrics to
      effectively teach medicine.
AB  - Medical schools must consider innovative ways to ensure that graduates are
      prepared to care for the aging population. One way is to offer a geriatrics
      clerkship as an option for the fulfillment of a medical school's internal
      medicine rotation requirement. The authors' purpose was to evaluate the
      geriatrics clerkship's impact on internal medicine knowledge and medical student
      attitudes toward older adults. Mean National Board of Medical Examiners (NBME)
      internal medicine subject exam scores from geriatrics and internal medicine
      students who matriculated from 2005 to 2011 were compared using student's t
      tests. Academic performance was controlled for using the United States Medical
      Licensing Exam Step 1 exam scores. Focus groups were conducted to explore student
      attitudes. Geriatrics students performed just as well on the NBME exam as their
      internal medicine colleagues, but reported greater comfort with elder care.
      Geriatrics students also reported more positive attitudes toward older adults.
      Completing an internal medicine requirement using a geriatrics clerkship is an
      innovation for medical school curriculum structure. 

PMID- 23972232
TI  - Cross-accent intelligibility of speech in noise: long-term familiarity and short
      term familiarization.
AB  - Listeners must cope with a great deal of variability in the speech signal, and
      thus theories of speech perception must also account for variability, which comes
      from a number of sources, including variation between accents. It is well known
      that there is a processing cost when listening to speech in an accent other than
      one's own, but recent work has suggested that this cost is reduced when listening
      to a familiar accent widely represented in the media, and/or when short amounts
      of exposure to an accent are provided. Little is known, however, about how these
      factors (long-term familiarity and short-term familiarization with an accent)
      interact. The current study tested this interaction by playing listeners
      difficult-to-segment sentences in noise, before and after a familiarization
      period where the same sentences were heard in the clear, allowing us to
      manipulate short-term familiarization. Listeners were speakers of either Glasgow
      English or Standard Southern British English, and they listened to speech in
      either their own or the other accent, thereby allowing us to manipulate long-term
      familiarity. Results suggest that both long-term familiarity and short-term
      familiarization mitigate the perceptual processing costs of listening to an
      accent that is not one's own, but seem not to compensate for them entirely, even
      when the accent is widely heard in the media. 

PMID- 23972231
TI  - Heat shock protein 90 inhibitors prevent LPS-induced endothelial barrier
      dysfunction by disrupting RhoA signaling.
AB  - Permeability of the endothelial monolayer is increased when exposed to the
      bacterial endotoxin LPS. Our previous studies have shown that heat shock protein
      (Hsp) 90 inhibitors protect and restore LPS-mediated hyperpermeability in bovine
      pulmonary arterial endothelial cells. In this study, we assessed the effect of
      Hsp90 inhibition against LPS-mediated hyperpermeability in cultured human lung
      microvascular endothelial cells (HLMVECs) and delineated the underlying molecular
      mechanisms. We demonstrate that Hsp90 inhibition is critical in the early phase,
      to prevent LPS-mediated hyperpermeability, and also in the later phase, to
      restore LPS-mediated hyperpermeability in HLMVECs. Because RhoA is a well known
      mediator of endothelial hyperpermeability, we investigated the effect of Hsp90
      inhibition on LPS-mediated RhoA signaling. RhoA nitration and activity were
      increased by LPS in HLMVECs and suppressed when pretreated with the Hsp90
      inhibitor, 17-allylamino-17 demethoxy-geldanamycin (17-AAG). In addition,
      inhibition of Rho kinase, a downstream effector of RhoA, protected HLMVECs from
      LPS-mediated hyperpermeability and abolished LPS-induced myosin light chain (MLC)
      phosphorylation, a target of Rho kinase. In agreement with these findings, 17-AAG
      or dominant-negative RhoA attenuated LPS-induced MLC phosphorylation. MLC
      phosphorylation induced by constitutively active RhoA was also suppressed by 17
      AAG, suggesting a role for Hsp90 downstream of RhoA. Inhibition of Src family
      kinases also suppressed RhoA activity and MLC phosphorylation. Together, these
      data indicate that Hsp90 inhibition prevents and repairs LPS-induced lung
      endothelial barrier dysfunction by suppressing Src-mediated RhoA activity and
      signaling. 

PMID- 23972233
TI  - Structures of spiroindicumides A and B, unprecedented carbon skeletal
      spirolactones, and determination of the absolute configuration by vibrational
      circular dichroism exciton approach.
AB  - Spiroindicumides A (1) and B (2), novel spirolactone polyketides, were isolated
      from a filamentous fungus, Chaetomium indicum, cultivated in the presence of a
      histone deacetylase inhibitor. Their structures including relative configurations
      were determined by spectroscopic analyses. Their absolute configurations were
      unambiguously assigned by the vibrational circular dichroism (VCD) exciton
      chirality method using only ca. 0.3 mg of each sample. This study presents the
      first application of the VCD exciton approach to novel natural products. A
      possible biosynthetic pathway of the new compounds was also proposed. 

PMID- 23972234
TI  - Hearing in the Mind's Ear: A PET Investigation of Musical Imagery and Perception.
AB  - Neuropsychological studies have suggested that imagery processes may be mediated
      by neuronal mechanisms similar to those used in perception. To test this
      hypothesis, and to explore the neural basis for song imagery, 12 normal subjects
      were scanned using the water bolus method to measure cerebral blood flow (CBF)
      during the performance of three tasks. In the control condition subjects saw
      pairs of words on each trial and judged which word was longer. In the perceptual
      condition subjects also viewed pairs of words, this time drawn from a familiar
      song; simultaneously they heard the corresponding song, and their task was to
      judge the change in pitch of the two cued words within the song. In the imagery
      condition, subjects performed precisely the same judgment as in the perceptual
      condition, but with no auditory input. Thus, to perform the imagery task
      correctly an internal auditory representation must be accessed. Paired-image
      subtraction of the resulting pattern of CBF, together with matched MRI for
      anatomical localization, revealed that both perceptual and imagery. tasks
      produced similar patterns of CBF changes, as compared to the control condition,
      in keeping with the hypothesis. More specifically, both perceiving and imagining
      songs are associated with bilateral neuronal activity in the secondary auditory
      cortices, suggesting that processes within these regions underlie the
      phenomenological impression of imagined sounds. Other CBF foci elicited in both
      tasks include areas in the left and right frontal lobes and in the left parietal
      lobe, as well as the supplementary motor area. This latter region implicates
      covert vocalization as one component of musical imagery. Direct comparison of
      imagery and perceptual tasks revealed CBF increases in the inferior frontal polar
      cortex and right thalamus. We speculate that this network of regions may be
      specifically associated with retrieval and/or generation of auditory information
      from memory. 

PMID- 23972235
TI  - The organization of brain activations in number comparison: event-related
      potentials and the additive-factors method.
AB  - Measuring reaction times (RTs) using the additive-factors method provides
      information about the sequence of processing stages in a cognitive task. Here, I
      describe how the simultaneous recording of event-related potentials (ERPs) in the
      same task can provide complementary information that cannot be obtained using RTs
      alone. Most notably, ERP data can reveal the absolute activation time and the
      coarse brain localization of processing stages. RTs and ERPs can also be used to
      cross-validate a serial-stage model. These notions were applied to a study of the
      temporal unfolding of brain activations in a number comparison task. ERPs were
      recorded from 64 scalp electrodes while normal subjects classified numbers as
      larger or smaller than 5. Specific scalp signatures and timing data were obtained
      for stages of word and digit identification, magnitude comparison, response
      programming, and error capture and correction. The observed localizations were
      compatible with previous neuropsychological and brain imaging data and provided
      new insights into the cerebral lateralization and timing of number processing. 

PMID- 23972236
TI  - Neural representations: some old problems revisited.
AB  - Hebb's (1949) cell assembly, originally conceived as an explanation for stimulus
      equivalence, also serves as a neural representation of stimuli. Association
      between cell assemblies was a major theme of Hebb's book, but the state of
      physiological knowledge at the time was such that no satisfactory basis for it
      could he devised. Subsequent theory has been more concerned with the recognition
      and "attractor" features of the cell assembly than its capacity to represent and
      associate concepts. This is unfortunate because while generalization is
      important, so is discrimination, which is not well served by an attractor model.
      This dilemma is avoided by postulating that stimulus representation and stimulus
      equivalence involve different neural circuits. Human beings can instantly form
      and use associations between many more concepts than there are synapses on the
      average cortical neuron, indicating that the associative links between engrams
      are sparse. The connections within an engram, on the other hand. must be dense to
      ensure that a weak input can activate all its neurons. It would appear that two
      processes are anatomically and physiologically different, which may account for
      the fact that engrams remain distinct in spite of being associated with each
      other. The fact that a single concept may have very many associations puts a
      heavy demand on the process of selective attention to avert complete chaos. I
      propose that attention is a manifestation of motivation. Motivation facilitates
      responses, which in turn facilitate engrams of associated stimuli. The enhanced
      engram activity is fed back through centrifugal paths to intensify sensory input
      that has previously played a part in executing the planned responses. Attention
      may also contribute to a mechanism that prevents the engrams of component parts
      of an object from being assimilated into the engram of the whole. 

PMID- 23972237
TI  - Individual differences in cerebral blood flow in area 17 predict the time to
      evaluate visualized letters.
AB  - Sixteen subjects closed their eyes and visualized uppercase letters of the
      alphabet at two sizes, as small as possible or as large as possible while
      remaining "visible." Subjects evaluated a shape characteristic of each letter
      (e.g., whether it has any curved lines), and responded as quickly as possible.
      Cerebral blood flow was normalized to the same value for each subject, and
      relative blood flow was computed for a set of regions of interest. The mean
      response time for each subject in the task was regressed onto the blood flow
      values. Blood flow in area 17 was negatively correlated with response time (r = 
      0.65), as was blood flow in area 19 (r = -0.66), whereas blood flow in the
      inferior parietal lobe was positively correlated with response time (r = 0.54).
      The first two effects persisted even when variance due to the other correlations
      was removed. These findings suggest that individual differences in the activation
      of specific brain loci are directly related to performance of tasks that rely on
      processing in those loci. 

PMID- 23972238
TI  - Interview with Michael I. Posner.
AB  - Michael Posner has been professor of psychology at the University of Oregon since
      1965. His work has generally been in the area of selective attention. During the
      1960s and 1970s, Posner's work relied primarily on chronometric methods and is
      best described in his Paul Fitts lectures published as Chronometric Explorations
      of Mind. From 1979 to 1985 Posner directed a laboratory at Good Samaritan
      Hospital and worked on the role of the parietal lobe and other structures
      involved in visual orienting. From 1985 to 1988 Posner directed a neuropsychology
      laboratory in St. Louis where he worked with Marc Raichle and Steve Petersen in
      developing PET methods appropriate to cognitive studies (see Images of Mind with
      M. Raichle). Since 1988, Posner has been working on combined spatial and temporal
      studies exploring the plasticity of human attention and skill acquisition.
      Posner's work has been recognized by membership in the U.S. National Academy of
      Sciences, APAs Distinguished Scientific Contribution Award and William James book
      award (with M. Raichle), and by the Vollum award for outstanding contribution to
      science and technology in the pacific northwest. 

PMID- 23972239
TI  - Cupping therapy and palliative care: what about hematologic malignancies?

PMID- 23972240
TI  - The potentized homeopathic drug, Lycopodium clavatum (5C and 15C) has anti-cancer
      effect on hela cells in vitro.
AB  - Cancer is a disease that needs a multi-faceted approach from different systems of
      medicine. The purpose of this study was to evaluate whether homeopathically
      potentized ultra-high dilutions of Lycopodium Clavatum (LC-5C and LC-15C,
      respectively) have any anti-cancer effects on HeLa cells. Cells were exposed to
      either LC-5C (diluted below Avogadro's limit, i.e., 10(-10)) or LC-15C (diluted
      beyond Avogadro's limit, i.e., 10(-30)) (drug-treated) or to 30% succussed
      ethanol ("vehicle" of the drug). The drug-induced modulation in the percent cell
      viability, the onset of apoptosis, and changes in the expressions of Bax, Bcl2,
      caspase 3, and Apaf proteins in inter-nucleosomal DNA, in mitochondrial membrane
      potentials and in the release of cytochrome-c were analyzed by utilizing
      different experimental protocols. Results revealed that administration of LC-5C
      and LC-15C had little or no cytotoxic effect in normal peripheral blood
      mononuclear cells, but caused considerable cell death through apoptosis in cancer
      (HeLa) cells, which was evident from the induction of DNA fragmentation, the
      increases in the expressions of protein and mRNA of caspase 3 and Bax, and the
      decreases in the expressions of Bcl2 and Apaf and in the release of cytochrome-c.
      Thus, the highly-diluted, dynamized homeopathic remedies LC-5C and LC-15C
      demonstrated their capabilities to induce apoptosis in cancer cells, signifying
      their possible use as supportive medicines in cancer therapy. 

PMID- 23972241
TI  - Anticancer potential of myricanone, a major bioactive component of Myrica
      cerifera: novel signaling cascade for accomplishing apoptosis.
AB  - Extract of Myrica cerifera bark has long been fruitfully used as a hepato
      protective and anti-cancer drug in various complementary and alternative systems
      of medicine. Myricanone, its principal bioactive compound, had also been reported
      to have apoptosis-promoting ability. We evaluated its anti-cancer potential in
      vitro in HepG2 liver cancer cells and tried to understand the signal cascades
      involved in accomplishing apoptosis. Further, we ascertained by using a (3-(4, 5
      dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay (MTT) assay if it
      had cytotoxic effects on normal noncancerous liver cells (WRL-68). We deployed
      various tools and protocols, like phase contrast, scanning electron and
      fluorescence microscopies, performed an annexinV-FITC/PI assay and cell cycle
      analysis, and estimated the reactive oxygen species (ROS) generation and
      mitochondrial membrane depolarization through flow cytometry. Further, analyses
      of cytochrome-c translocation and of HSP70 and caspase expressions were also done
      by using immunoblota and Enzyme linked immunosorbent assay (ELISA). Results
      revealed that myricanone induced apoptosis in HepG2 cells through generation of
      ROS, depolarization of the mitochondrial membrane, early release of cytochrome-c,
      down-regulation of HSP70 and activation of a caspase cascade; it had no, or
      insignificant, cytotoxic effects in WRL-68 cells in vitro and in mice in vivo.
      Thus, myricanone has great potential for use in formulating an effective drug
      against both hepatotoxicity and hepatocellular cancer. 

PMID- 23972242
TI  - Effects of extracts and fractions of Gynura procumbens on rat atrial contraction.
AB  - There is currently a great deal of research interest in utilizing plant compounds
      against human diseases, including hypertension. The present study investigated
      the effects of different extracts and fractions from leaves of Gynura procumbens
      Merr. on rat atrial contraction in vitro. Isolated left and right atria, mounted
      in a 20-ml organ bath, were allowed to equilibrate for 15 min before the
      application of the extracts or fractions. The extracts (petroleum-ether extract
      (PE) and methanol extract (ME)) and the fractions (chloroform fraction (CHL),
      ethyl-acetate fraction (EA), n-butanol fraction (NB) and water fraction (WA) of
      the methanol extract) were tested at three concentrations (0.25, 0.5 and 1.0
      mg/ml), with a beta-adrenergic agonist (isoprenaline) as a control. All data on
      contraction responses were log-transformed and analyzed. When exposed to the
      different extracts, both atria tended to exhibit greater contractive responses
      with the NB whereas cardiac contractions had a tendency to be reduced with most
      other extracts. For a given extract, the contraction responses were particularly
      greater at 0.5 mg/ml for the right atrium and at 1 mg/ml for the left atrium.
      Further analysis focusing on the NB fraction revealed that positive inotropism
      was greater in left atria exposed to highly-concentrated F2 and F3 sub-fractions.
      Taken together, our results suggest that NB extracts and fractions from the G.
      procumbens-leaf methanol extract have positive inotropic activities and, hence,
      can be considered as an alternative/traditional medicine against increased blood
      pressure in humans or can be used in strategies aimed at finding antihypertensive
      biomolecules from an accessible source. 

PMID- 23972243
TI  - Evaluation of Bacopa monniera for its synergistic activity with rivastigmine in
      reversing aluminum-induced memory loss and learning deficit in rats.
AB  - The objective of this study was to evaluate the synergistic activity of Bacopa
      monniera with Rivastigmine against aluminum-chloride (AlCl3)-induced cognitive
      impairment in rats. Adult male Wistar rats were divided into ten groups (n = 10)
      and subjected to their assigned treatments for 42 days. On the 20(th) day of the
      respective drug treatments, all the animals were trained in the Morris water maze
      (retention latency) and the elevated plus maze (transfer latency). After the
      initial training, the retention latency (RL) and the transfer latency (TL) were
      evaluated on the 21(st) and the 42(nd) days of the study. Chronic administration
      of AlCl3 caused significant memory impairment associated with increased RL in the
      Morris water maze task and increased TL in the elevated plus maze test.
      Interestingly, animals treated with oral administration of B. monniera (100 and
      200 mg/kg), Rivastigmine (5 mg/kg) or a combination of B. monniera (100 mg/kg)
      with Rivastigmine (5 mg/kg) showed significant protection against AlCl3-induced
      memory impairment compared to animal treated with AlCl3per se. Additionally, the
      neuroprotective effect of B. monniera (100 and 200 mg/kg) was significantly
      improved when supplemented with Rivastigmine (5 mg/kg). These findings suggest
      that treatment with a combination of B. monniera with Rivastigmine may be highly
      beneficial compared to their per-se treatment. 

PMID- 23972244
TI  - Assessment of the antiulcer potential of Moringa oleifera root-bark extract in
      rats.
AB  - In the present study, an ethanolic root-bark extract of Moringa oleifera (MO) was
      examined for its antiulcer potential in albino Wistar rats using two experimental
      models: ethanol-induced and pylorus ligation-induced gastric ulceration. The
      extract was orally administered at three different doses (150, 350, and 500
      mg/kg) for 15 consecutive days. The antiulcer effects in rats treated with
      different doses of the extract and omeprazole (30 mg/kg, p.o.) were determined
      and compared statistically with the antiulcer effects in the control rats treated
      with saline (NaCl, 0.9%). The MO at doses of 350 and 500 mg/kg decreased the
      ulcer index significantly as compared to the control group (p < 0.01). The
      percentage protections against gastric ulcers were 82.58%, 85.13%, and 86.15% for
      MO doses of 150, 350, and 500 mg/kg, respectively, in the pylorus-ligated ulcer
      model and 55.75%, 59.33%, and 78.51%, respectively, in the ethanol-induced ulcer
      model. The MO significantly reduced the free acidity, total acidity, and ulcer
      index (p < 0.01) and increased the pH of gastric content compared with the
      control group. This study suggests that MO possesses valuable antiulcer,
      antisecretory, and cytoprotective activity. Thus, an ethanolic root-bark extract
      of Moringa oleifera can be used as source for an antiulcer drug. 

PMID- 23972245
TI  - Invited commentary.

PMID- 23972246
TI  - Reporting standards for adverse events after medical device use in the peripheral
      vascular system.

PMID- 23972247
TI  - Traumatic pseudoaneurysm with 30 years of evolution.

PMID- 23972248
TI  - Ataxia and vertigo due to anomalous origin of the left vertebral artery.

PMID- 23972249
TI  - Clinical implications of the angiosome model in peripheral vascular disease.
AB  - Vascular surgery has seen a revolutionary transformation in its approach to
      peripheral vascular disease over the last 2 decades, fueled by technological
      innovation and a willingness by the field to adopt these changes. However, the
      underlying pathology behind critical limb ischemia and the significant rate of
      unhealed wounds and secondary amputations despite apparently successful
      revascularization needs to be addressed. In seeking to improve outcomes, it may
      be beneficial to examine our approach to vascular disease at the fundamental
      level of anatomy, the angiosome, to better dictate reperfusion strategies beyond
      a simple determination of open vs endovascular procedure. We performed a
      systematic review of the current literature concerning the significance of the
      angiosome concept in the realm of vascular surgery. The dearth of convincing
      evidence in the form of prospective trials and large patient populations, and the
      lack of a consistent, comparable vocabulary to contrast study findings, prevent
      recommendation of the conceptual model at a wider level for guidance of
      revascularization attempts. Further well-structured, prospective studies are
      required as well as emerging imaging strategies, such as indocyanine green dye
      based fluorescent angiography or hyperspectral imaging, to allow wider adoption
      of the angiosome model in vascular operations. 

PMID- 23972250
TI  - Debate: Whether level I evidence comparing thoracic endovascular repair and
      medical management is necessary for uncomplicated type B aortic dissections.
AB  - Type B aortic dissections continue to be one of the most challenging clinical
      scenarios confronting vascular surgeons. In the era of open surgery, the
      therapeutic options were limited to medical management of hypertension and large
      open thoracoabdominal operations. In the current endovascular era, the operative
      strategies have become less invasive but the questions regarding therapeutic
      approaches have become more numerous and complex. In patients with acute
      uncomplicated type B aortic dissections, we are still unsure as to which patients
      are best treated with medical therapy alone or with the addition of early
      endovascular repair. Data from single centers and registries have provided some
      guidance; however, questions remain. Perhaps level 1 evidence from well-designed
      randomized controlled trials will answer all of our questions. This is the topic
      of the current debate. 

PMID- 23972251
TI  - Editors' commentary.

PMID- 23972252
TI  - Regarding "Low incidence of paraplegia after thoracic endovascular aneurysm
      repair with proactive spinal cord protective protocols".

PMID- 23972253
TI  - Reply: To PMID 23490292.

PMID- 23972254
TI  - Regarding "Prediction of graft patency and mortality after distal
      revascularization and interval ligation for hemodialysis access-related hand
      ischemia" and "Using distal revascularization with interval ligation as the
      primary treatment of hand ischemia after dialysis access creation".

PMID- 23972255
TI  - Simultaneous bilateral distal biceps tendon ruptures repaired using an endobutton
      technique: a case report.
AB  - INTRODUCTION: The simultaneous rupture of both distal biceps tendons is a rare
      clinical entity that is difficult to treat and can have poor outcomes. A variety
      of treatment and rehabilitation options exist and have been reported for single
      sided and staged bilateral repairs, but none have described an approach for acute
      bilateral ruptures. Repairing distal biceps tendon ruptures using a single
      anterior incision and a cortical suspensory button technique has become
      increasingly popular in recent years. We present a report of our surgical
      approach using an endobutton technique and rehabilitation algorithm for this
      unusual injury pattern. CASE PRESENTATION: A 43-year-old Caucasian man presented
      with acute onset bilateral elbow pain while lifting a large sheet of drywall off
      the ground. He initially felt a 'pop' on the right and almost immediately felt
      another on the left after having to quickly shift the weight. He was unable to
      continue working and sought medical attention. His pain was predominantly in his
      bilateral antecubital fossae and he had significant swelling and ecchymoses. His
      clinical examination demonstrated no palpable tendon, a retracted biceps muscle
      belly, and clear supination weakness. Magnetic resonance imaging was performed
      and showed bilateral distal biceps tendon ruptures with retraction on both sides.
      After discussion with our patient, we decided that both sides would be repaired
      using a single anterior incision with endobutton fixation, first his right
      followed by his left six weeks later. CONCLUSION: Overall, our patient did very
      well and had returned to full manual work by our last follow-up at 30 months.
      Although he was never able to return to competitive recreational hockey and was
      left with mild lateral antebrachial cutaneous nerve dysesthesias on his right, he
      felt he was at 85% of his premorbid level of function. We describe what we
      believe to be, to the best of our knowledge, the first case of simultaneous
      bilateral distal biceps tendon ruptures successfully treated with a single
      incision endobutton technique, which represents a valid option in managing this
      difficult problem.

PMID- 23972256
TI  - Identification of MFG-E8 as a novel therapeutic target for diseases.
AB  - INTRODUCTION: Milk fat globule-epidermal growth factor-factor 8 (MFG-E8), a
      peripheral membrane glycoprotein has been widely studied in recent years due to
      its omnipresent locations, express and multiple functions. Traditionally, MFG-E8
      was identified as an outstanding factor for phagocytosis of apoptotic cells and a
      significant factor in immune systems. Recent studies with some new findings have
      shed an interesting light on the old peripheral membrane glycoprotein in various
      diseases. AREAS COVERED: In inflammatory and the systemic lupus erythematosus
      type autoimmune disease, age-related diseases and tumors, MFG-E8 plays a
      multifunctional role in attenuating inflammation and improving prognosis, healing
      wound and remodeling arterial and enhancing tumorigenicity and cancer metastasis.
      This review provides a comprehensive view on the latest advances in the field.
      The summarized knowledge will help to explore the potential therapeutic roles of
      MFG-E8 and to design MFG-E8-based strategies for the treatment of these diseases.
      EXPERT OPINION: Though the exact roles of MFG-E8 have not been fully elucidated
      in diseases. MFG-E8 may serve as a promising therapeutic strategy.

PMID- 23972257
TI  - Vacuum ultraviolet spectroscopy and photochemistry of zinc dihydride and related
      molecules in low-temperature matrices.
AB  - Optical absorption spectra of thin film samples, formed by the codeposition of
      zinc vapor with D2 and CH4, have been recorded with synchrotron radiation. With
      sufficiently low metal vapor flux, samples deposited at 4 K were found to consist
      exclusively of isolated zinc atoms for both solids. The atomic absorption bands
      in the quantum solids D2 and CH4 were found to exhibit large bandwidths, behavior
      related to the high lattice frequencies of these low mass solids. The reactivity
      of atomic zinc was promoted with (1)P state photolysis leading to the first
      recording of electronic absorption spectra for the molecules ZnD2 and CH3ZnH in
      the vacuum ultraviolet (VUV) region. (3)P state luminescence of atomic zinc
      observed in the Zn/CH4 system points to the involvement of the spin triplet state
      in the relaxation of CH3ZnH system as it evolves into the C3v ground state. This
      state is not involved in the relaxation of the higher symmetry molecule ZnD2.
      Time dependent density functional theory (TD-DFT) calculations were conducted to
      predict the electronic transitions of the inserted molecular species. Comparisons
      with experimental data indicate the predicted transition energies are
      approximately 0.5 eV less than the recorded values. Possible reasons for the
      discrepancy are discussed. The molecular photochemistry of ZnD2 and CH3ZnH
      observed in the VUV was modeled successfully with a simple four-valence electron
      AH2 Walsh-type diagram. 

PMID- 23972258
TI  - Specific proteomic response of Unio pictorum mussel to a mixture of glyphosate
      and microcystin-LR.
AB  - Cyanobacterial toxins and pesticides regularly impact freshwaters. Microcystin-LR
      is one of the most toxic and common cyanobacterial toxins whereas glyphosate is
      the active ingredient of a widely use herbicide. As filter feeders, freshwater
      mussels are particularly exposed. Like many native bivalve species, Unio pictorum
      suffers from a continuous decline in Europe. In order to get a deeper insight of
      its response to contaminants, U. pictorum was exposed to either 10 MUg L(-1) of
      microcystin-LR or 10 MUg L(-1) of glyphosate or a mixture of both. Proteins of
      the digestive glands were extracted and analyzed by DIGE. Gel analysis revealed
      103 spots with statistical variations, and the response seems to be less toward
      glyphosate than to microcystin-LR. Specific spots have variations only when
      exposed to the mixture, showing that there is an interaction of both contaminants
      in the responses triggered. The proteins of 30 spots have been identified. They
      belong mostly to the cytoskeleton family, but proteins of the oxidative pathway,
      detoxification, and energetic metabolism were affected either by glyphosate or
      microcystin-LR or by the mixture. These results demonstrate the importance to
      study contaminants at low concentrations representative of those found in the
      field and that multicontaminations can lead to different response pathways. 

PMID- 23972259
TI  - Tell me your life: including life stories in an adult development and aging
      course.
AB  - The goals of this study were to determine the learning impact of an assignment
      that consisted of interviewing and analyzing older people's life stories, and to
      explore how the assignment was evaluated by students. Participants in the study
      were 122 first-year social education students enrolled in an adult development
      and aging course. They evaluated the assignment using an eight-adjective
      questionnaire and were asked about the benefits of the task. Their answers to the
      questionnaire were then reviewed using content analysis. The results indicated
      that marks on the life story assignment predicted marks on an exam about basic
      course concepts. Students considered that the assignment was interesting, useful,
      and integrated into the course, although most of them also thought that it was
      very time-consuming. They identified benefits related to the explicit goals of
      the course (improvement in the learning of developmental concepts, the
      acquisition of research-related skills, and the deactivation of aging
      stereotypes) and personal, growth-related benefits. The authors discuss the
      difficulties posed by the assignment and its usefulness as a complement to more
      traditional, lecture-based teaching methods in adult development and aging
      courses. 

PMID- 23972260
TI  - Summer deficit-irrigation strategies in a hedgerow olive cv. Arbequina orchard:
      effect on oil quality.
AB  - Different irrigation treatments were applied to a superintensive orchard of
      'Arbequina' olives ( Olea europaea L.) during three seasons (2007-2009) to
      examine the effect of the amount of water and the moment of irrigation in summer
      on the virgin olive oil (VOO) quality. A control was made (CON) with irrigation
      to maintain the root zone close to field capacity; two water deficit treatments
      were employed with irrigation at 30% of CON, either from the end of fruit drop to
      the end of July (DI-J) or from the end of July until the beginning of oil
      synthesis (DI-A); and other treatment was tested by irrigating 50% of CON in July
      and August (DI-JA). DI-J oils exhibited significantly higher oxidative stability,
      which coincided with significantly higher contents in phenol derivatives.
      Consequently, the selection of the moment and intensity of summer irrigation
      played an important role in the nutritional and sensory quality of the VOO. 

PMID- 23972261
TI  - Incidence of postoperative acute kidney injury in patients with chronic kidney
      disease undergoing minimally invasive valve surgery.
AB  - BACKGROUND: We hypothesize that minimally invasive valve surgery in patients with
      chronic kidney disease (CKD) is superior to a conventional median sternotomy.
      METHODS: We retrospectively analyzed 1945 consecutive patients who underwent
      isolated valve surgery. Included were patients with CKD stages 2 to 5. In
      hospital mortality, composite complication rates, and intensive care unit and
      total hospital lengths of stay of those who underwent a minimally invasive
      approach were compared with those who underwent a standard median sternotomy.
      Resource use was approximated based on intensive care unit and total hospital
      lengths of stay. RESULTS: There were 688 patients identified; 510 (74%) underwent
      minimally invasive surgery, and 178 (26%) underwent a median sternotomy. There
      was no significant difference in mortality. Minimally invasive surgery was
      associated with fewer composite complications (33.1% vs 49.4%; odds ratio, 0.5; P
      <= .001), shorter intensive care unit (48 [interquartile range {IQR}, 33-74]
      hours vs 71 [IQR, 42-96] hours; P < .01), and hospital (8 [IQR, 6-9] days vs 10
      [IQR, 8-15] days; P < .001) lengths of stay, and a lower incidence of acute
      kidney injury (8% vs 14.7%; odds ratio, 0.5; P = .01), compared with median
      sternotomy. In a multivariable analysis, minimally invasive surgery was
      associated with a 60% reduction in the risk of development of postoperative acute
      kidney injury. CONCLUSIONS: In patients with CKD undergoing isolated valve
      surgery, minimally invasive valve surgery is associated with reduced
      postoperative complications and lower resource use.

PMID- 23972262
TI  - ALADIN: wish granted in inherited polycystic kidney disease?

PMID- 23972265
TI  - Milestones for nephrology training programs: a modest proposal.

PMID- 23972264
TI  - Proteinase-activated receptor-1, CCL2, and CCL7 regulate acute neutrophilic lung
      inflammation.
AB  - PAR1 plays a central role in mediating the interplay between coagulation and
      inflammation, but its role in regulating acute neutrophilic inflammation is
      unknown. We report that antagonism of PAR1 was highly effective at reducing acute
      neutrophil accumulation in a mouse model of LPS-induced lung inflammation. PAR1
      antagonism also reduced alveolar-capillary barrier disruption in these mice. This
      protection was associated with a reduction in the expression of the chemokines,
      CCL2 and CCL7, but not the proinflammatory cytokines, TNF and IL-6, or the
      classic neutrophil chemoattractants, CXCL1 and CXCL2. Antibody neutralization of
      CCL2 and CCL7 significantly reduced LPS-induced total leukocyte and neutrophil
      accumulation, recovered from the bronchoalveolar lavage fluid of challenged mice.
      Immunohistochemical analysis revealed that CCL2 predominantly localized to
      alveolar macrophages and pulmonary epithelial cells, whereas CCL7 was restricted
      to the pulmonary epithelium. In keeping with these observations, the intranasal
      administration of recombinant CCL2 (rCCL2) and rCCL7 led to the accumulation of
      neutrophils within the lung airspaces of naive mice in the absence of any
      underlying inflammation. Flow cytometry analysis further demonstrated an increase
      in Ly6G(hi) neutrophils expressing the chemokine receptors, CCR1 and CCR2,
      isolated from mouse lungs compared with circulating neutrophils. Conversely, the
      expression of CXCR2 decreased on neutrophils isolated from the lung compared with
      circulating neutrophils. Furthermore, this switch in chemokine receptor
      expression was accentuated after acute LPS-induced lung inflammation.
      Collectively, these findings reveal a novel role for PAR1 and the chemokines,
      CCL2 and CCL7, during the early events of acute neutrophilic inflammation. 

PMID- 23972263
TI  - Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal
      dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled,
      multicentre trial.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease slowly progresses to end
      stage renal disease and has no effective therapy. A pilot study suggested that
      the somatostatin analogue octreotide longacting release (LAR) could be
      nephroprotective in this context. We aimed to assess the effect of 3 years of
      octreotide-LAR treatment on kidney and cyst growth and renal function decline in
      participants with this disorder. METHODS: We did an academic, multicentre,
      randomised, single-blind, placebo-controlled, parallel-group trial in five
      hospitals in Italy. Adult (>18 years) patients with estimated glomerular
      filtration rate (GFR) of 40 mL/min per 1.73 m(2) or higher were randomly assigned
      (central allocation by phone with a computerised list, 1:1 ratio, stratified by
      centre, block size four and eight) to 3 year treatment with two 20 mg
      intramuscular injections of octreotide-LAR (n=40) or 0.9% sodium chloride
      solution (n=39) every 28 days. Study physicians and nurses were aware of the
      allocated group; participants and outcome assessors were masked to allocation.
      The primary endpoint was change in total kidney volume (TKV), measured by MRI, at
      1 year and 3 year follow-up. Analyses were by modified intention to treat. This
      study is registered with ClinicalTrials.gov, NCT00309283. FINDINGS: Recruitment
      was between April 27, 2006, and May 12, 2008. 38 patients in the octreotide-LAR
      group and 37 patients in the placebo group had evaluable MRI scans at 1 year
      follow-up, at this timepoint, mean TKV increased significantly less in the
      octreotide-LAR group (46.2 mL, SE 18.2) compared with the placebo group (143.7
      mL, 26.0; p=0.032). 35 patients in each group had evaluable MRI scans at 3 year
      follow-up, at this timepoint, mean TKV increase in the octreotide-LAR group
      (220.1 mL, 49.1) was numerically smaller than in the placebo group (454.3 mL,
      80.8), but the difference was not significant (p=0.25). 37 (92.5%) participants
      in the octreotide-LAR group and 32 (82.1%) in the placebo group had at least one
      adverse event (p=0.16). Participants with serious adverse events were similarly
      distributed in the two treatment groups. However, four cases of cholelithiasis or
      acute cholecystitis occurred in the octreotide-LAR group and were probably
      treatment-related. INTERPRETATION: These findings provide the background for
      large randomised controlled trials to test the protective effect of somatostatin
      analogues against renal function loss and progression to end-stage kidney
      disease. FUNDING: Polycystic Kidney Disease Foundation.

PMID- 23972266
TI  - Severe hypokalemia in a patient with subarachnoid hemorrhage.
AB  - Hypokalemia is a common electrolyte disorder in the intensive care unit. Its
      cause often is complex, involving both potassium losses from the body and shifts
      of potassium into cells. We present a case of severe hypokalemia of sudden onset
      in a patient being treated for subarachnoid hemorrhage in the surgical intensive
      care unit in order to illustrate the diagnosis and management of severe
      hypokalemia of unclear cause. Our patient received agents that promote renal
      potassium losses and treatments associated with a shift of potassium into cells.
      We outline the steps in diagnosis and management, focusing on the factors
      regulating the transcellular distribution of potassium in the body. 

PMID- 23972267
TI  - The future role of mesenchymal stem cells in the management of shoulder
      disorders.
AB  - PURPOSE: Biologics may help to optimize the healing environment after rotator
      cuff repair. Mesenchymal stem cells (MSCs) may have the potential to regenerate a
      physiological enthesis, thereby improving healing at the repair site after
      rotator cuff repair. METHODS: The PubMed database was searched in May 2013. Only
      in vivo and in vitro studies reporting on stem cell use in the rotator cuff of
      humans or animals were included. Exclusion criteria consisted of the following:
      Level V evidence, systematic reviews, and studies reporting preliminary results.
      RESULTS: This query resulted in 141 citations. Of these, 90 were excluded based
      on the title of the study. A final group of 17 studies was included in this
      review (9 in vivo animal studies, 5 in vitro human studies, 1 in vitro animal
      study, 1 study reporting in vitro human and in vivo animal results, and 1 study
      reporting on clinical outcomes of human patients). CONCLUSIONS: The current
      literature regarding therapeutic use of MSCs in shoulder surgery is limited.
      Although in vivo animal studies have shown some promising approaches to enhance
      tendon-to-bone healing, the use of MSCs for shoulder surgery should still be
      regarded as an experimental technique. Further basic and clinical research is
      needed until a procedure can be defined for the routine use of these cells in
      shoulder surgery.

PMID- 23972268
TI  - "I" is for "innovation".

PMID- 23972269
TI  - Putting emotional intelligence to work.

PMID- 23972270
TI  - Opportunities to improve snacks and beverages in schools.

PMID- 23972271
TI  - Looking back to move forward.

PMID- 23972272
TI  - The subjective global assessment predicts in-hospital mortality better than other
      nutrition-related risk indexes in noncritically ill inpatients who receive total
      parenteral nutrition in Spain (prospective multicenter study).
AB  - Malnutrition in hospitalized patients is associated with an increased risk of
      death and complications. The purpose of this study was to determine which
      nutrition-related risk index predicts mortality better in patients receiving
      total parenteral nutrition. This prospective, multicenter study involved
      noncritically ill patients who were prescribed total parenteral nutrition. Data
      were collected on Subjective Global Assessment (SGA), Nutritional Risk Index,
      Geriatric Nutritional Risk Index, body mass index, albumin and prealbumin, as
      well as in-hospital mortality, length of stay, and infectious complications. Of
      the 605 patients included in the study, 18.8% developed infectious complications
      and 9.6% died in the hospital. SGA, albumin, Nutritional Risk Index and Geriatric
      Nutritional Risk Index were associated with longer hospital stay. Prealbumin
      levels were associated with infectious complications. Multiple logistic
      regression analysis showed (after adjustment for age, sex, C-reactive protein
      levels, mean blood glucose levels, use of corticoids, prior comorbidity,
      carbohydrates infused, diagnosis, and infectious complications) that the SGA,
      Geriatric Nutritional Risk Index, body mass index, albumin, and prealbumin were
      associated with an increased risk for in-hospital mortality. SGA was the tool
      that best predicted mortality and adequately discriminated the values of the
      other nutrition-related risk indexes studied. The SGA is a clinically effective
      and simple tool for nutrition assessment in noncritically ill patients receiving
      total parenteral nutrition and detects the risk of inpatient mortality better
      than others. 

PMID- 23972273
TI  - Dietary nitrates and nitrites-harmful? Helpful? Or paradox?

PMID- 23972274
TI  - Safety of biologics: elaboration and validation of a questionnaire assessing
      patients' self-care safety skills: the BioSecure questionnaire. An initiative of
      the French Rheumatology Society Therapeutic Education section.
AB  - BACKGROUND: Biologics are known to entail specific risks (e.g. infections).
      Patients should possess self-care safety skills to develop appropriate behaviors
      in situations of risks (e.g. fever). To date, there is no adequate tool to assess
      these skills. OBJECTIVES: To elaborate a questionnaire to measure knowledge and
      skills regarding safety issues, for patients treated by biologics. METHODS: Three
      step process. (1) A steering group of 10 rheumatologists, one pharmacist and two
      allied health professionals elaborated an exhaustive list of safety skills.
      Through a 3-round Delphi process involving the steering group, 14 patients on
      biologics and 14 other allied health professionals, the list of skills was
      reduced. (2) A corresponding series of questions and of clinical situations with
      multiple-choice answers were designed. (3) Preliminary validation was performed
      against the physician's opinion on skills, and reliability was assessed. RESULTS:
      The list includes 24 skills e.g. how to deal with fever, planned surgery, dental
      care, travel, minor traumas, and immunizations. A 55-question questionnaire was
      constructed. Preliminary validation (62 patients) showed the questionnaire was
      filled in 10 minutes (median) and correlated to the physician's opinion of skills
      (R=0.47, P<0.0001) but not to disease status or disease duration. The median
      score was 75% (range 20%-96%). The questionnaire was reliable: intraclass
      correlation coefficient, 0.83 (95% CI: 0.63-0.93). CONCLUSION: A simple (multiple
      choice questionnaire) and valid tool investigating a core set of safety skills
      has been developed. This tool could be useful to detect further educational needs
      regarding biologics safety, and to assess the efficacy of oriented educational
      interventions.

PMID- 23972275
TI  - A longitudinal, experiential quality improvement curriculum meeting ACGME
      competencies for geriatrics fellows: lessons learned.
AB  - Quality improvement (QI) initiatives are critical in the care of older adults who
      are more vulnerable to substandard care. QI education meets aspects of core
      Accreditation Council of Graduate Medical Education competencies and prepares
      learners for the rising focus on performance measurement in health care. The
      authors developed, implemented, and evaluated a QI curriculum for geriatrics
      fellows. The evidence-based curriculum included didactics and a fellow-led QI
      intervention based on audit and feedback through the Practice Improvement Module
      in Care of the Vulnerable Elderly. QI knowledge, attitudes, and behaviors were
      assessed before and after the improvement project. Fellows' knowledge of QI
      improved (p = .0156), but behavior did not change significantly across a short
      term improvement project. A structured focus group with fellows revealed themes
      of accountability and the importance of interprofessional teamwork in QI. QI
      education for geriatrics fellows can be feasible, well received, and prepare
      future physician leaders for patient-centered care, performance measurement, and
      effecting systems change. 

PMID- 23972276
TI  - A randomized trial to optimize HIV/TB care in South Africa: design of the
      Sizanani trial.
AB  - BACKGROUND: Despite increases in HIV testing, only a fraction of people newly
      diagnosed with HIV infection enter the care system and initiate antiretroviral
      therapy (ART) in South Africa. We report on the design and initial enrollment of
      a randomized trial of a health system navigator intervention to improve linkage
      to HIV care and TB treatment completion in Durban, South Africa. METHODS/DESIGN:
      We employed a multi-site randomized controlled trial design. Patients at 4
      outpatient sites were enrolled prior to HIV testing. For all HIV-infected
      participants, routine TB screening with sputum for mycobacterial smear and
      culture were collected. HIV-infected participants were randomized to receive the
      health system navigator intervention or usual care. Participants in the navigator
      arm underwent a baseline interview using a strengths-based case management
      approach to assist in identifying barriers to entering care and devising
      solutions to best cope with perceived barriers. Over 4 months, participants in
      the navigator arm received scheduled phone and text messages. The primary outcome
      of the study is linkage and retention in care, assessed 9 months after
      enrollment. For ART-eligible participants without TB, the primary outcome is 3
      months on ART as documented in the medical record; participants co-infected with
      TB are also eligible to meet the primary outcome of completion of 6 months of TB
      treatment, as documented by the TB clinic. Secondary outcomes include mortality,
      receipt of CD4 count and TB test results, and repeat CD4 counts for those not ART
      eligible at baseline. We hypothesize that a health system navigator can help
      identify and positively affect modifiable patient factors, including self
      efficacy and social support, that in turn can improve linkage to and retention in
      HIV and TB care. DISCUSSION: We are currently evaluating the clinical impact of a
      novel health system navigator intervention to promote entry to and retention in
      HIV and TB care for people newly diagnosed with HIV. The details of this study
      protocol will inform clinicians, investigators, and policy makers of strategies
      to best support HIV-infected patients in resource-limited settings. TRIAL
      REGISTRATION: Clinicaltrials.gov. unique identifier: NCT01188941.

PMID- 23972277
TI  - Reliability of magnetic resonance imaging for the detection of hypopituitarism in
      children with optic nerve hypoplasia.
AB  - PURPOSE: It is essential to identify hypopituitarism in children with optic nerve
      hypoplasia (ONH) because they are at risk for developmental delay, seizures, or
      death. The purpose of this study is to determine the reliability of
      neurohypophyseal abnormalities on magnetic resonance imaging (MRI) for the
      detection of hypopituitarism in children with ONH. DESIGN: Cross-sectional study.
      PARTICIPANTS: One hundred one children with clinical ONH who underwent MRI of the
      brain and orbits and a detailed pediatric endocrinologic evaluation. METHODS:
      Magnetic resonance imaging studies were performed on 1.5-Tesla scanners. The
      imaging protocol included sagittal T1-weighted images, axial fast fluid
      attenuated inversion-recovery/T2-weighted images, and diffusion-weighted images
      of the brain. Orbital imaging included fat-saturated axial and coronal images and
      high-resolution axial T2-weighted images. The MRI studies were reviewed by 2
      pediatric neuroradiologists for optic nerve hypoplasia, absent or ectopic
      posterior pituitary, absent pituitary infundibulum, absent septum pellucidum,
      migration anomalies, and hemispheric injury. Medical records were reviewed for
      clinical examination findings and endocrinologic status. All patients underwent a
      clinical evaluation by a pediatric endocrinologist and a standardized panel of
      serologic testing that included serum insulin-like growth factor-1, insulin-like
      growth factor binding protein-3, prolactin, cortisol, adrenocorticotropic
      hormone, thyroid-stimulating hormone, and free thyroxine levels. Radiologists
      were masked to patients' endocrinologic status and funduscopic findings. MAIN
      OUTCOME MEASURES: Sensitivity and specificity of MRI findings for the detection
      of hypopituitarism. RESULTS: Neurohypophyseal abnormalities, including absent
      pituitary infundibulum, ectopic posterior pituitary bright spot, and absent
      posterior pituitary bright spot, occurred in 33 children. Magnetic resonance
      imaging disclosed neurohypophyseal abnormalities in 27 of the 28 children with
      hypopituitarism (sensitivity, 96%). A normal neurohypophysis occurred in 67 of 73
      children with normal endocrinologic function (specificity, 92%). CONCLUSIONS:
      Neurohypophyseal abnormalities on MRI are sensitive and specific indicators of
      hypopituitarism in children with ONH.

PMID- 23972278
TI  - Design, synthesis, and insecticidal evaluation of new pyrazole derivatives
      containing imine, oxime ether, oxime ester, and dihydroisoxazoline groups based
      on the inhibitor binding pocket of respiratory complex I.
AB  - On the basis of complex I receptor protein binding site and commercial
      tebufenpyrad and tolfenpyrad, four series of novel pyrazole-5-carboxamides
      containing imine, oxime ether, oxime ester, and dihydroisoxazoline were designed
      and synthesized via the key intermediate 4-chloro-3-ethyl-N-(4-formylbenzyl)-1
      methyl-1H-pyrazole-5-carboxamide. The structures of target compounds were
      confirmed by 1H NMR and high-resolution mass spectrum (HRMS). The results of
      bioassays indicated that the target compounds possessed good-to-excellent
      activities against a broad spectrum of insects such as cotton bollworm
      (Helicoverpa armigera), spider mite (Tetranychus cinnabarinus), bean aphid (Aphis
      craccivora), and mosquito (Culex pipiens pallens), but gave different structure
      activity relationships for each species. Compounds containing imine showed high
      insecticidal activity against cotton bollworm. Especially, stomach activity of
      compounds 5-1c was 60% at 11 mg kg-1. The compounds also had good activities
      against bean aphid and mosquito. The foliar contact activity of compounds 5-1a, 5
      1b, 5-1e, 5-3c, and 5-3d against bean aphid were 90, 100, 90, 90, and 90%,
      respectively, at 200 mg kg-1. The activity of compound containing
      dihydroisoxazoline moiety (5-4) against mosquito was 60% at 1 mg kg-1, which was
      near that of tebufenpyrad. The introduction of dihydroisoxazoline structure (5-4)
      was advantageous to improve the activity of the compound against adult mites
      compared with other structures; the miticidal activity of 5-4- against adult
      mites was 60% at 50 mg kg-1.

PMID- 23972279
TI  - Cryogenic ion chemistry and spectroscopy.
AB  - The use of mass spectrometry in macromolecular analysis is an incredibly
      important technique and has allowed efficient identification of secondary and
      tertiary protein structures. Over 20 years ago, Chemistry Nobelist John Fenn and
      co-workers revolutionized mass spectrometry by developing ways to non
      destructively extract large molecules directly from solution into the gas phase.
      This advance, in turn, enabled rapid sequencing of biopolymers through tandem
      mass spectrometry at the heart of the burgeoning field of proteomics. In this
      Account, we discuss how cryogenic cooling, mass selection, and reactive
      processing together provide a powerful way to characterize ion structures as well
      as rationally synthesize labile reaction intermediates. This is accomplished by
      first cooling the ions close to 10 K and condensing onto them weakly bound,
      chemically inert small molecules or rare gas atoms. This assembly can then be
      used as a medium in which to quench reactive encounters by rapid evaporation of
      the adducts, as well as provide a universal means for acquiring highly resolved
      vibrational action spectra of the embedded species by photoinduced mass loss.
      Moreover, the spectroscopic measurements can be obtained with readily available,
      broadly tunable pulsed infrared lasers because absorption of a single photon is
      sufficient to induce evaporation. We discuss the implementation of these methods
      with a new type of hybrid photofragmentation mass spectrometer involving two
      stages of mass selection with two laser excitation regions interfaced to the
      cryogenic ion source. We illustrate several capabilities of the cryogenic ion
      spectrometer by presenting recent applications to peptides, a biomimetic
      catalyst, a large antibiotic molecule (vancomycin), and reaction intermediates
      pertinent to the chemistry of the ionosphere. First, we demonstrate how site
      specific isotopic substitution can be used to identify bands due to local
      functional groups in a protonated tripeptide designed to stereoselectively
      catalyze bromination of biaryl substrates. This procedure directly reveals the
      particular H-bond donor and acceptor groups that enforce the folded structure of
      the bare ion as well as provide contact points for noncovalent interaction with
      substrates. We then show how photochemical hole-burning involving only
      vibrational excitations can be used in a double-resonance mode to systematically
      disentangle overlapping spectra that arise when several conformers of a dipeptide
      are prepared in the ion source. Finally, we highlight our ability to
      systematically capture reaction intermediates and spectroscopically characterize
      their structures. Through this method, we can identify the pathway for water
      network-mediated, proton-coupled transformation of nitrosonium, NO(+) to HONO, a
      key reaction controlling the cations present in the ionosphere. Through this
      work, we reveal the critical role played by water molecules occupying the second
      solvation shell around the ion, where they stabilize the emergent product ion in
      a fashion reminiscent of the solvent coordinate responsible for the barrier to
      charge transfer in solution. Looking to the future, we predict that the capture
      and characterization of fleeting intermediate complexes in the homogeneous
      catalytic activation of small molecules like water, alkanes, and CO2 is a likely
      avenue rich with opportunity. 

PMID- 23972281
TI  - EMAP/EMAPA ontology of mouse developmental anatomy: 2013 update.
AB  - BACKGROUND: The Edinburgh Mouse Atlas Project (EMAP) ontology of mouse
      developmental anatomy provides a standard nomenclature for describing normal and
      mutant mouse embryo anatomy. The ontology forms the core of the EMAP atlas and is
      used for annotating gene expression data by the mouse Gene Expression Database
      (GXD), Edinburgh Mouse Atlas of Gene Expression (EMAGE) and other database
      resources. FINDINGS: The original EMAP ontology listed anatomical entities for
      each developmental stage separately, presented as uniparental graphs organized as
      a strict partonomy. An "abstract" (i.e. non-stage-specific) representation of
      mouse developmental anatomy has since been developed. In this version (EMAPA) all
      instances for a given anatomical entity are presented as a single term, together
      with the first and last stage at which it is considered to be present. Timed
      component anatomies are now derived using staging information in the "primary"
      non-timed version. Anatomical entities are presented as a directed acyclic graph
      enabling multiple parental relationships. Subsumption classification as well as
      partonomic and other types of relationships can now be represented. Most concept
      names are unique, with compound names constructed using standardized nomenclature
      conventions, and alternative names associated as synonyms. CONCLUSIONS: The
      ontology has been extended and refined in a collaborative effort between EMAP and
      GXD, with additional input from others. Efforts are also underway to improve the
      revision process with regards to updating and editorial control. The revised
      EMAPA ontology is freely available from the OBO Foundry resource, with
      descriptive information and other documentation presented in associated Wiki
      pages (http://www.obofoundry.org/wiki/index.php/EMAPA:Main_Page).

PMID- 23972280
TI  - Genome-wide analyses of Shavenbaby target genes reveals distinct features of
      enhancer organization.
AB  - BACKGROUND: Developmental programs are implemented by regulatory interactions
      between Transcription Factors (TFs) and their target genes, which remain poorly
      understood. While recent studies have focused on regulatory cascades of TFs that
      govern early development, little is known about how the ultimate effectors of
      cell differentiation are selected and controlled. We addressed this question
      during late Drosophila embryogenesis, when the finely tuned expression of the TF
      Ovo/Shavenbaby (Svb) triggers the morphological differentiation of epidermal
      trichomes. RESULTS: We defined a sizeable set of genes downstream of Svb and used
      in vivo assays to delineate 14 enhancers driving their specific expression in
      trichome cells. Coupling computational modeling to functional dissection, we
      investigated the regulatory logic of these enhancers. Extending the repertoire of
      epidermal effectors using genome-wide approaches showed that the regulatory
      models learned from this first sample are representative of the whole set of
      trichome enhancers. These enhancers harbor remarkable features with respect to
      their functional architectures, including a weak or non-existent clustering of
      Svb binding sites. The in vivo function of each site relies on its intimate
      context, notably the flanking nucleotides. Two additional cis-regulatory motifs,
      present in a broad diversity of composition and positioning among trichome
      enhancers, critically contribute to enhancer activity. CONCLUSIONS: Our results
      show that Svb directly regulates a large set of terminal effectors of the
      remodeling of epidermal cells. Further, these data reveal that trichome formation
      is underpinned by unexpectedly diverse modes of regulation, providing fresh
      insights into the functional architecture of enhancers governing a terminal
      differentiation program.

PMID- 23972282
TI  - Motor system alterations in retired former athletes: the role of aging and
      concussion history.
AB  - BACKGROUND: Retired athletes with a history of sports concussions experience
      cognitive and motor declines with aging, and the risk of severe neurodegenerative
      conditions is magnified in this population. The present study investigated the
      effects of aging on motor system metabolism and function in former university
      level athletes who sustained their last concussion several decades prior to
      testing. METHODS: To test the hypothesis that age and remote concussions induce
      functional as well as metabolic alterations of the motor system, we used proton
      magnetic resonance spectroscopy to detect metabolic abnormalities in the primary
      motor cortex and the serial reaction time task (SRTT) to evaluate motor learning.
      RESULTS: Our results indicate that motor learning is significantly reduced in
      former concussed athletes relative to controls. In addition, glutamate/H2O ratio
      in M1 was disproportionately reduced in concussed athletes with advancing age and
      was found to strongly correlate with motor learning impairments. CONCLUSION:
      Findings from this study provide evidence that the acquisition of a repeated
      motor sequence is compromised in the aging concussed brain and that its
      physiological underpinnings could implicate disproportionate reductions of M1
      glutamate concentrations with advancing age.

PMID- 23972283
TI  - Individual and joint activity of terpenoids, isolated from Calamintha nepeta
      extract, on Arabidopsis thaliana.
AB  - Four terpenoids, camphor, pulegone, trans-caryophyllene and farnesene, previously
      found in Calamintha nepeta (L.) Savi methanolic extract and essential oils were
      assayed on germination and root growth of Arabidopsis thaliana (L.) Heynh. None
      of the terpenes, singularly or in combination, was able to inhibit the
      germination process. Farnesene and trans-caryophyllene caused a strong inhibitory
      effect on root growth, and pulegone, at the highest concentrations, reduced
      lateral root formation. Although the mixture of camphor-trans-caryophyllene with
      or without farnesene did not cause any effect on root growth, the addition of
      pulegone induced a marked synergistic activity. Moreover, the addition, at low
      concentration, of farnesene to pulegone-camphor-trans-caryophyllene mixture
      further increased the inhibitory effect on root elongation. These results
      suggested that the inhibitory effects caused by C. nepeta methanolic extract may
      depend on the combined action of different molecules. 

PMID- 23972284
TI  - Challenges and opportunities for oral pre-exposure prophylaxis in the prevention
      of HIV infection: where are we in Europe?
AB  - Following US Food and Drugs Administration approval in July 2012 of daily oral
      tenofovir and emtricitabine for pre-exposure prophylaxis (PrEP) to prevent HIV
      infection in high-risk individuals in the USA, there has been much controversy
      about the implementation of this PrEP regimen in other countries throughout the
      world, and in Europe in particular. In this review, we focus on the challenges
      and opportunities of a daily oral PrEP regimen to curb the rising incidence of
      HIV infection in high-risk groups, and particularly in men who have sex with men.
      A number of issues would need to be addressed before PrEP could be implemented,
      including assessing the real effectiveness and cost-effectiveness of daily PrEP,
      the sustainability of daily adherence, the risk of selecting resistance, the long
      term safety, and the risk of change in sexual behavior that might offset the
      benefit of PrEP. Alternatives to a daily oral PrEP regimen are being explored. 

PMID- 23972285
TI  - Duration and method of tissue storage alters placental morphology - implications
      for clinical and research practice.
AB  - We assessed whether placental morphology is affected by placental storage before
      fixation. Fresh tissue from uncomplicated pregnancies (n = 10) was fixed
      immediately and further samples were stored dry, in PBS or culture medium for 24,
      48 or 72 h at 4  degrees C. Placental morphology quantified using image analysis
      software found no difference in syncytial nuclear aggregates, cytokeratin 7, CD45
      or Ki67 immunostaining irrespective of duration or mode of storage. The number of
      blood vessels per villus (CD31) was reduced in all conditions after 72 h (p <
      0.05). Distal villous hypoplasia increased after 72 h (p < 0.05). Ideally,
      storage time should be minimised to <=48 h prior to morphological or qualitative
      analysis.

PMID- 23972286
TI  - No change in calreticulin with fetal growth restriction in human and rat
      pregnancies.
AB  - INTRODUCTION: Calreticulin is a ubiquitously expressed protein that was detected
      in the circulation and is significantly increased in maternal blood during human
      pregnancy compared to the non-pregnant state. Calreticulin is further increased
      in the plasma of women with the pregnancy-related disorder pre-eclampsia compared
      to normotensive pregnancy. The aims of this study were to compare calreticulin in
      human pregnancy with calreticulin in rat pregnancy, and to compare calreticulin
      during fetal growth restriction with normal control pregnancies. METHODS: Women
      were recruited who either had normal pregnancies or had pregnancies complicated
      with fetal growth restriction; maternal blood samples and placentas were
      collected. Blood was also taken from women who were not-pregnant. Growth
      restriction was induced in pregnant rats by uterine vessel ligation; blood and
      placental samples were collected. Blood was also taken from non-pregnant rats.
      Western blot was used to quantify the placental expression of calreticulin and
      the concentrations of calreticulin in plasma. RESULTS: Although calreticulin was
      significantly increased in maternal plasma during human pregnancy compared to the
      non-pregnant state; it did not increase in plasma during rat pregnancy. These
      results suggest that there may be differences in the role of extracellular
      calreticulin in human compared to rat pregnancy. Calreticulin was not
      significantly altered in either placental extracts or maternal plasma in both the
      human and rat pregnancies complicated by fetal growth restriction compared to
      gestational matched control pregnancies. CONCLUSION: This study found that there
      was no change in calreticulin during human pregnancy complicated with fetal
      growth restriction or when growth restriction is induced in rats.

PMID- 23972287
TI  - Lipocalin2 enhances the matrix metalloproteinase-9 activity and invasion of
      extravillous trophoblasts under hypoxia.
AB  - OBJECTIVES: The invasion of extravillous trophoblasts (EVTs) to the decidua and
      spiral arteries in early pregnancy is a crucial step for a successful pregnancy;
      however, its mechanisms are not fully understood. Lipocalin2 (LCN2), a
      multifunctional secretory protein known as neutrophil gelatinase-associated
      lipocalin (NGAL), reportedly enhanced invasiveness via the activation of matrix
      metalloproteinase-9 (MMP-9) in several cancer cells. In this study, the
      expression and function of LCN2 in early placenta were analyzed. METHODS: Early
      placental tissues between 7 and 10 weeks of gestation were obtained from normal
      pregnant women who underwent elective termination. The expression of LCN2 was
      examined using immunostaining and RT-PCR. EVTs isolated from these placental
      tissues and a choriocarcinoma cell line (JAR) were used to investigate the
      effects of LCN2 on proliferation, invasion potential, and MMP-9 activity under
      hypoxia using a WST-1 assay, Matrigel invasion assay, and gelatin gel zymography,
      respectively. RESULTS: The immunohistochemical expression of LCN2 was observed in
      the cytoplasm of EVTs, cytotrophoblasts and the decidua, but not in
      syncytiotrophoblasts. The addition of recombinant LCN2 did not affect
      proliferation, but enhanced the invasiveness (500 ng/mL, p < 0.01) and MMP-9
      activity of primary cultured EVTs and JAR in a dose-dependent manner. Silencing
      LCN2 using shRNA reduced the invasiveness (p < 0.01) and MMP-9 activity of JAR.
      In addition, the hypoxic condition (2% O2) increased LCN2 expression (p < 0.01),
      MMP-9 activity, and invasive ability (p < 0.01). CONCLUSIONS: LCN2 was involved
      in the invasiveness of EVTs, especially under hypoxia, via increased MMP-9
      activity.

PMID- 23972289
TI  - Provision of critical care services for the obstetric population.
AB  - Management of the peripartum patient is a challenging aspect of critical care
      that requires consideration of both the physiological changes associated with
      pregnancy as well as the well-being of the foetus. In the UK, for every maternal
      death, approximately 118 near-miss events or severe acute maternal morbidities
      (SAMMs) occur. While a dedicated anaesthetic cover is usually provided on larger
      labour wards in the UK and US, a close communication with intensive care and
      other medical specialties must still be maintained. Medical outreach teams and
      early warning scores may help facilitate the early identification of clinical
      deterioration and prompt treatment. Ultimately level of care is allocated
      according to the clinical need, not the location, which may be a designated room,
      a normal labour room or a recovery area. Specialist obstetric units that provide
      high-dependency care facilities show lower rates of maternal transfer to critical
      care units and improved continuity of care before and after labour. The benefits
      of obstetric high-dependency units (HDUs) are likely to be determined by a number
      of logistic aspects of the hospital organisation, including hospital size and
      available resources. There remains a striking contrast in the burden of maternal
      mortality and morbidity and intensive care unit (ICU) resources between high- and
      low-income countries. The countries with the highest maternal mortality rates
      have the lowest number of ICU beds per capita. In under-resourced countries,
      patients admitted to ICUs tend to have higher illness severity scores, suggesting
      delayed admission to the ICU. The appropriate training of midwives is essential
      for successful HDUs located within labour wards.

PMID- 23972288
TI  - BreakTrans: uncovering the genomic architecture of gene fusions.
AB  - Producing gene fusions through genomic structural rearrangements is a major
      mechanism for tumor evolution. Therefore, accurately detecting gene fusions and
      the originating rearrangements is of great importance for personalized cancer
      diagnosis and targeted therapy. We present a tool, BreakTrans, that
      systematically maps predicted gene fusions to structural rearrangements. Thus,
      BreakTrans not only validates both types of predictions, but also provides
      mechanistic interpretations. BreakTrans effectively validates known fusions and
      discovers novel events in a breast cancer cell line. Applying BreakTrans to 43
      breast cancer samples in The Cancer Genome Atlas identifies 90 genomically
      validated gene fusions. BreakTrans is available at
      http://bioinformatics.mdanderson.org/main/BreakTrans. 

PMID- 23972290
TI  - Associations of interleukin-4 receptor gene polymorphisms (Q551R, I50V) with
      rheumatoid arthritis: evidence from a meta-analysis.
AB  - BACKGROUND AND AIMS: Published data on the associations between interleukin-4
      receptor (IL-4R) gene polymorphisms (Q551R, I50V) and rheumatoid arthritis (RA)
      risk are controversial. To quantitatively evaluate the relationships, a meta
      analysis was performed. METHODS: Studies were identified from the databases of
      PubMed, MEDLINE, Chinese Biomedical Literature Database, and Chinese National
      Knowledge Infrastructure, with the last report up to June 2012. The effect
      summary odds ratio (OR) and 95% confidence interval (CI) were obtained. RESULTS:
      A total of six separate comparisons involving 2173 patients and 1892 controls
      were included to assess the association of IL-4R gene Q551R polymorphism and RA
      susceptibility. Overall, no significantly elevated RA risk was found in the meta
      analysis. The pooled OR for the minor R allele was 0.942 (95% CI: 0.848-1.047,
      p=0.268) in patients with RA. After stratification by ethnicity, there was still
      no significant association detected in the European population (OR=0.979, 95% CI:
      0.875-1.094). As for I50V polymorphism, there were four comparisons involving
      1653 patients and 1584 controls in this meta-analysis. The pooled OR for the V
      allele was 1.104 (95% CI: 1.001-1.217) in RA, the V allele of the IL-4R gene I50V
      variant might be a risk factor for RA. However, the relationship between the V
      allele of IL-4R gene I50V polymorphism and rheumatoid factor positive in patients
      with RA was not identified through a minor meta-analysis, including four
      independent relevant comparisons. CONCLUSIONS: This meta-analysis indicates that
      the I50V polymorphism of IL-4R gene may confer susceptibility to RA; up to now,
      there is still not enough evidence to reveal the association of the IL-4R gene
      Q551R polymorphism with RA risk.

PMID- 23972291
TI  - Polymorphisms in the IL2RA and IL2RB genes in inflammatory bowel disease risk.
AB  - Associations with different autoimmune diseases of polymorphisms in genes
      encoding the IL2RA and IL2RB subunits (located in 10p15 and 22q13, respectively),
      were identified through genome-wide studies. Polymorphisms in these two genes
      were studied in 107 inflammatory bowel disease (IBD) patients (39 Crohn's disease
      [CD] and 68 ulcerative colitis [UC]) and in 162 ethnically healthy controls from
      Tunisia (Sfax). Two of the 15 IL2RA single-nucleotide polymorphisms (SNPs)
      genotyped (rs4749924 and rs706778) were significantly associated with UC
      (pcorr=0.018 and 0.048, respectively), but no evidence of association with CD was
      observed. The IL2RA GTCT haplotype was also more frequent in UC patients compared
      to controls (2.6% vs. 0%; p=0.002). One of the 6 IL2RB SNPs genotyped (rs743776)
      was significantly associated with CD (pcorr= 0.039), but no evidence of
      association with UC was observed. No significant association between IL2RB
      haplotypes was observed among investigated groups. Our study identified markers
      in the IL2RA and IL2RB genes that are significantly associated with UC and CD,
      respectively. Our results supporting IL2RA and IL2RB as promising candidate genes
      for IBD and suggesting a potential role of IL2R in the pathogenesis of IBD,
      likely involves regulatory T cells. 

PMID- 23972292
TI  - Environmental risk factors and lung diseases in children: from guidelines to
      health effects.
AB  - During the last decades research all over the world has highlighted the
      deleterious effects of outdoor and indoor pollution on respiratory health of
      adults and children. The World Health Organization (WHO) "Air quality guidelines
      for Europe" played a fundamental role in providing information and guidance to
      authorities involved in the air pollution field and they are considered the key
      source on which the European Commission's directive on air quality is based.
      Children appear to be most vulnerable to the harmful effects of outdoor
      pollutants, which can cause both acute exacerbations, as well as chronic
      respiratory symptoms and diseases. Possible mechanisms include the induction of
      oxidative stress, and/or allergic sensitization, as well as increased
      susceptibility to infections. Cigarette smoke is one of the environmental
      pollutant influencing morbidity and death rate in childhood as responsible for
      adverse health effects in both prenatal and postnatal. There is growing
      epidemiological evidence that indoor allergen exposure may contribute to the
      development of allergic respiratory symptoms. In Italy the housing and social
      situation, with regard to the aspects related to exposure to secondhand smoke or
      the presence of fungal spores, moisture linked to household vapor and poor
      ventilation of the rooms are problems still not completely resolved. From a
      medical point of view the field of pediatrics has certainly made great strides in
      promoting the health of children and pediatricians to have a central role for
      pursuing this objective. 

PMID- 23972293
TI  - Viral bronchiolitis in children: a common condition with few therapeutic options.
AB  - Even though bronchiolitis is a disease that has been recognized for many years,
      there are still few therapeutic strategies beyond supportive therapies.
      Bronchiolitis is the most frequent cause of hospital admission in children less
      than 1 year of age. The incidence is estimated to be about 150 degrees  million
      cases a year worldwide, and 2-3% of these cases require hospitalization. It is
      acknowledged that viruses cause bronchiolitis, but most of the studies focus on
      RSV. The RSV causes a more severe form of bronchiolitis in children with risk
      factors including prematurity, cardiovascular disease and immunodeficiency. Other
      viruses involved in causing bronchiolitis include RV, hMPV, hBoV and co
      infections. The RV seems to be associated with a less severe acute disease, but
      there is a correlation between the early infection and subsequent wheezing
      bronchitis and asthma in later childhood and adulthood. The supportive therapies
      used are intravenous fluids and oxygen supplement administered by nasal cannula
      or CPAP in most complicated patients. Additional pharmacological therapies
      include epinephrine, 3% hypertonic saline and corticosteroids. The Epinephrine
      seems to have the greatest short-term benefits and reduces the need of hospital
      admission, whereas hypertonic saline and corticosteroids seem to reduce the
      length of hospital stay. As bronchiolitis is such a prevalent disease in children
      and RV seems to play an important role, perhaps more studies should center around
      the RV's contribution to the initial disease and following pathology. 

PMID- 23972294
TI  - Evaluating sucking maturation using two pressure thresholds.
AB  - BACKGROUND: The Medoff-Cooper Nutritive Sucking Apparatus (M-CNSA) has been used
      to objectively measure sucking maturation in preterm infants. The M-CNSA is able
      to accurately detect sucking pressures less than 20mmHg, however lower pressure
      thresholds have not previously been used in research. AIMS: To determine if
      differences are observed in the number of sucks and maturation in the number of
      sucks over time when the minimum pressure threshold used to detect a suck is
      7mmHg compared to 20mmHg using the M-CNSA. STUDY DESIGN: Descriptive. SUBJECTS: A
      convenience sample of 171 healthy premature infants born between 29 and 34weeks
      gestational period who were part of a larger randomized controlled study. OUTCOME
      MEASURES: The number of sucks detected during weekly five-minute oral feeding
      observations using 7mmHg and 20mmHg. RESULTS: Significantly more sucks were
      detected using the 7mmHg vs 20mmHg threshold at all time points. At both pressure
      thresholds, the mean number of sucks detected during the five minute feeding
      observation increased over time. The difference in the number of sucks detected
      at 7 and 20mmHg did not change over time (p=0.50). CONCLUSIONS: Using the lower
      threshold of 7mmHg compared to 20mmHg resulted in more sucks detected while
      consistently measuring improvement in sucking over time. Detection of more sucks
      and sucks at a lower pressure threshold allows clinicians and researchers to more
      accurately assess oral feeding skills among premature infants.

PMID- 23972295
TI  - Compassionate care: empowering students through nurse education.
AB  - Compassionate care is widely discussed in the media, at policy level, in practice
      and in academic institutions. In order to provide care of this quality, students
      must be equipped with the skills necessary to build effective relationships with
      patients and others and to successfully manage the challenges they can encounter
      in this process. This article describes an evaluation of a teaching approach
      designed to enhance students' ability to deliver compassionate care. The student
      voice is used to illuminate their experiences. 

PMID- 23972296
TI  - ChiS histidine kinase negatively regulates the production of chitinase ChiC in
      Streptomyces peucetius.
AB  - Computational analysis of sequence homology of the chiSRC gene cluster, encoding
      a chitinase in Streptomyces peucetius, showed that the gene cluster could be a
      two-component regulon comprising a sensor kinase (chiS) and a response regulator
      (chiR). To prove that the ChiSRC is an authentic two-component system, the chiS
      gene was cloned and expressed in E.coli and the purified protein was used for
      biochemical analysis. In this report, we provide biochemical evidence to show
      that the sensor kinase encoded by chiS gene indeed is a histidine kinase capable
      of autophosphorylation and the histidine 144 residue of the ChiS protein is the
      phosphate acceptor. An insertion mutation at the chiS locus led to overproduction
      chitinase protein in S. peucetius implying that the chiC gene is negatively
      regulated by the two-component system. 

PMID- 23972297
TI  - Defining the errors in the registration process during imageless computer
      navigation in total knee arthroplasty: a cadaveric study.
AB  - Computer assisted arthroplasty was introduced as a means to optimally align
      implants in order to improve function and longevity. The error during the manual
      registration of landmarks and its effect on component alignment was investigated
      in this study. Five fresh frozen lower limbs were used and the registration
      process was performed five times by five surgeons. The error range of the
      mechanical axis of the femur in the coronal plane was 5.2 degrees of valgus to
      2.9 degrees of varus whilst the transepicondylar axis error was 11.1 degrees of
      external to 6.3 of internal rotation. Those figures suggest that the registration
      error alone can have a significant effect on the alignment of the implant. 

PMID- 23972298
TI  - Complications, mortality, and costs for outpatient and short-stay total knee
      arthroplasty patients in comparison to standard-stay patients.
AB  - The purpose of the present study is to determine the differences in cost,
      complications, and mortality between knee arthroplasty (TKA) patients who stay
      the standard 3-4 nights in a hospital compared to patients who undergo an
      outpatient procedure, a shortened stay or an extended stay. TKA patients were
      identified in the Medicare 5% sample (1997-2009) and separated into the following
      groups: outpatient, 1-2 days, 3-4 days, or 5+ days inpatient. At two years, costs
      associated with the outpatient and the 1-2 day stay groups were $8527 and $1967
      lower than the 3-4 day stay group, respectively. Out to 2 years, the outpatient
      and 1-2 day stay groups reported less pain and stiffness, respectively, though
      the 1-2 day group also had a higher risk for revision.

PMID- 23972299
TI  - Comparison of one-stage revision with antibiotic cement versus two-stage revision
      results for infected total hip arthroplasty.
AB  - Eighty three patients of infected total hip arthroplasty (THA) treated by implant
      removal and staged revision were retrospectively analyzed. Clinical
      characteristics and treatment outcomes were compared between three groups: 17 one
      stage revisions (one-stage group), 44 two-stage revisions with second stage
      reimplantation (two-stage reimplanted group), and 22 planned two-stage but no
      reimplantation (two-stage non-reimplanted group). The rate of infection control
      was 82% (14/17) in the one-stage group, 75% (33/44) in the two-stage reimplanted
      group, and 68% (15/22) in the two-stage non-reimplanted group (P=0.60). The mean
      of latest Harris hip score was 77, 60, and 58 (P=0.14), and the UCLA activity
      score was 4.0, 4.2, and 3.6 (P=0.74) for each group, respectively. Results of
      this study suggest that one-stage revision arthroplasty can be a treatment option
      in selected cases of infected THA with a satisfactory infection control rate and
      functional outcomes comparable to those of two-stage revision. 

PMID- 23972300
TI  - Pyothorax-associated lymphoma (PAL) with biclonal Epstein-Barr virus infection:
      characterization of a novel PAL cell line with unique features.
AB  - Pyothorax-associated lymphoma (PAL) is a representative form of diffuse large B
      cell lymphoma associated with chronic inflammation, in which the Epstein-Barr
      virus (EBV) genome is consistently detectable in the lymphoma cells of all PAL
      cases. Cell lines and animal models would be useful for understanding better this
      rare lymphoma, but reports of PAL-derived cell lines are scarce. We report a new
      PAL cell line, designated Pal-2, with unique phenotypic expression. Pal-2 is the
      first PAL cell line that carries a biclonal EBV infection with abundant viral
      genome and that exhibits tumorigenic capacity once injected into nude mice. 

PMID- 23972301
TI  - Natural course of myopic traction maculopathy and factors associated with
      progression or resolution.
AB  - PURPOSE: To investigate the natural course of myopic traction maculopathy and to
      identify the factors associated with its progression or resolution in 207 highly
      myopic eyes. DESIGN: Retrospective, consecutive case series. METHODS: We
      investigated 207 highly myopic eyes with myopic traction maculopathy by optical
      coherence tomography (OCT) and followed the patients for at least 24 months. The
      size of the macular retinoschisis was categorized according to its extent and
      location relative to the fovea. The clinical data, status of the myopic traction
      maculopathy, and changes in the posterior vitreous and inner limiting membrane
      (ILM) were analyzed during the natural course of the disease process. RESULTS:
      During a mean follow-up of 36.2 +/- 6.2 months, 8 of 207 eyes (3.9%) showed a
      decrease or complete resolution of the macular retinoschisis. Of these 8 eyes, 6
      had release of retinal traction in the OCT images, and 4 of the 6 eyes developed
      posterior vitreous detachment. A spontaneous disruption of the ILM occurred in 2
      eyes before the improvement of the myopic traction maculopathy. Of the 207 eyes,
      24 (11.6%) experienced progression of the myopic traction maculopathy. The eyes
      with more extensive macular retinoschisis showed progression significantly more
      commonly (42.9%) than the eyes having less extensive macular retinoschisis areas
      (6.7%). CONCLUSIONS: The natural course of myopic traction maculopathy varies,
      and eyes with more extensive macular retinoschisis tend to progress more
      commonly. A complete resolution of macular retinoschisis can occur after a
      release of traction on the retina. These findings can be used to determine
      whether surgery should be performed.

PMID- 23972302
TI  - Optical coherence tomography morphologic grading of macular commotio retinae and
      its association with anatomic and visual outcomes.
AB  - PURPOSE: To investigate the morphologic characteristics of macular commotio
      retinae using spectral-domain optical coherence tomography (SDOCT) and develop a
      grading system for traumatic photoreceptor damage. DESIGN: Retrospective,
      observational case series. METHODS: setting: Seoul National University Bundang
      Hospital. patients: Forty-nine patients with macular commotio retinae, examined
      by SDOCT within 7 days of the initial traumatic event. observations: A 4-step
      grading system was based on the morphology revealed by SDOCT. Best-corrected
      visual acuity (BCVA) and structural integrity of the 3 photoreceptor layers (cone
      outer segment tips [COST], inner/outer segment [IS-OS] junction, external
      limiting membrane [ELM]) were evaluated at baseline, at 1 month, and at the final
      visit. Visual and anatomic outcomes at 1 month and at the final visit were
      compared among subgroups. main outcome measures: The severity of photoreceptor
      damage as revealed by SDOCT and BCVA. RESULTS: The following 4 distinct
      photoreceptor morphologic features were observed: increase in IS-OS junction
      reflectivity with the disappearance of the thin hyporeflective optical space (n =
      8, grade 1), COST defect only (n = 5, grade 2), COST and IS-OS junction defects
      (n = 16, grade 3), and COST, IS-OS junction, and ELM defects (n = 20, grade 4).
      Eyes with higher grades at baseline had significantly worse visual (final BCVA, P
      = .002) and anatomic outcomes (complete photoreceptor recovery, P < .001).
      CONCLUSIONS: The number of disrupted photoreceptor layers, as determined using
      SDOCT images, can be used to grade macular commotio retinae. This system may be
      useful in documenting the baseline severity of photoreceptor damage and in
      predicting visual and anatomic outcomes.

PMID- 23972303
TI  - Likelihood ratios for glaucoma diagnosis using spectral-domain optical coherence
      tomography.
AB  - PURPOSE: To present a methodology for calculating likelihood ratios for glaucoma
      diagnosis for continuous retinal nerve fiber layer (RNFL) thickness measurements
      from spectral-domain optical coherence tomography (spectral-domain OCT). DESIGN:
      Observational cohort study. METHODS: A total of 262 eyes of 187 patients with
      glaucoma and 190 eyes of 100 control subjects were included in the study.
      Subjects were recruited from the Diagnostic Innovations Glaucoma Study. Eyes with
      preperimetric and perimetric glaucomatous damage were included in the glaucoma
      group. The control group was composed of healthy eyes with normal visual fields
      from subjects recruited from the general population. All eyes underwent RNFL
      imaging with Spectralis spectral-domain OCT. Likelihood ratios for glaucoma
      diagnosis were estimated for specific global RNFL thickness measurements using a
      methodology based on estimating the tangents to the receiver operating
      characteristic (ROC) curve. RESULTS: Likelihood ratios could be determined for
      continuous values of average RNFL thickness. Average RNFL thickness values lower
      than 86 MUm were associated with positive likelihood ratios (ie, likelihood
      ratios greater than 1), whereas RNFL thickness values higher than 86 MUm were
      associated with negative likelihood ratios (ie, likelihood ratios smaller than
      1). A modified Fagan nomogram was provided to assist calculation of posttest
      probability of disease from the calculated likelihood ratios and pretest
      probability of disease. CONCLUSION: The methodology allowed calculation of
      likelihood ratios for specific RNFL thickness values. By avoiding arbitrary
      categorization of test results, it potentially allows for an improved integration
      of test results into diagnostic clinical decision making.

PMID- 23972304
TI  - Accomodative tone in children under general anesthesia.
AB  - PURPOSE: To determine the effect of general anesthesia on the accommodative tone
      in children. DESIGN: Cohort study in an academic practice. METHODS: In children
      under 12 years of age who were undergoing general anesthesia, cycloplegic
      refraction was measured using streak retinoscopy during an office visit. Within 6
      months, streak retinoscopy without cycloplegia was performed under general
      anesthesia. The main outcome measure was the difference between retinoscopy under
      anesthesia and cycloplegic retinoscopy in children. RESULTS: In 41 children with
      an average age of 3.7 years (range, 0.8 to 11 years) retinoscopy under anesthesia
      yielded significantly more myopic measurements than cycloplegic retinoscopy for
      the sphere and spherical equivalent (P < 0.0001 for both) but was in good
      agreement with cycloplegic retinoscopy for cylinder power and axis. The average
      difference between retinoscopy under anesthesia and cycloplegic retinoscopy was 
      0.98 diopters (D) (95% limit of agreement, -3.08 D to +1.10 D) for the sphere,
      0.08 D (95% limit of agreement, -0.67 D to +0.82 D) for the cylinder, and -0.94 D
      (95% limit of agreement, -3.01 D to +1.13 D) for the spherical equivalent.
      Retinoscopy under anesthesia was within 1 D of cycloplegic retinoscopy in 25
      subjects (61%) for the sphere, in all subjects for the cylinder, and in 28
      subjects (68.3%) for the spherical equivalent. CONCLUSIONS: Although general
      anesthesia reduced the accommodative tone in most children, it was still
      significant in some as compared to the tone found in cycloplegic retinoscopy. If
      an accurate measurement is essential, cycloplegia is recommended when measuring
      refraction in children under general anesthesia.

PMID- 23972305
TI  - Morphologic characterization of dome-shaped macula in myopic eyes with serous
      macular detachment.
AB  - PURPOSE: To analyze dome-shaped maculas topographic features and related serous
      retinal detachment (SRD) in eyes with myopic staphyloma. DESIGN: Retrospective,
      observational case series. METHODS: We reviewed the records of 48 eyes in 33
      patients with dome-shaped maculas who were referred because of decreased vision.
      Ophthalmologic examination included axial length measurement, spectral domain
      optical coherence tomography (OCT), and fluorescein and indocyanine green
      angiography. The height of the macular bulge was measured, and the choroidal
      thickness was mapped. RESULTS: Patient mean age was 55.0 +/- 13.6 years. Mean
      axial length was 27.49 +/- 2.53 mm. Mean best-corrected visual acuity (BCVA) was
      0.50 +/- 0.33 logMAR. Three dome-shaped macula patterns were observed: round dome
      in 10/48 (20.8%) eyes; horizontal oval-shaped dome in 30/48 (62.5%) eyes; and
      vertical oval-shaped dome in 8/48 (16.7%) eyes. The mean macular bulge height was
      407.7 +/- 215.1 MUm (120-1130) and was significantly greater in vertical oval
      shaped domes. The mean central choroidal thickness (CCT) was 146.5 +/- 56.0 MUm,
      significantly greater than at 3 mm nasal and temporal to the fovea (P < 0.0001).
      The CCT was positively correlated to macular bulge height but not to BCVA. Foveal
      SRD was present in 25/48 eyes and significantly increased for macular bulge
      height greater than 350 MUm (P = 0.0047). BCVA was significantly lower when SRD
      was present (P = 0.043). CONCLUSIONS: Most dome-shaped maculas did not display a
      round but a horizontal or vertical oval-shaped dome and could be missed on a
      single OCT scan. Chronic foveal SRD was associated with decreased vision and was
      more common when the macular bulge was highly elevated.

PMID- 23972306
TI  - Identification of persons with incident ocular diseases using health care claims
      databases.
AB  - PURPOSE: To assess the extent to which incidence rates calculated for common
      ocular diseases by using claims data may be overestimated according to the length
      of the disease-free look-back period used in the analysis. DESIGN: Retrospective
      longitudinal cohort analysis. METHODS: Billing records of 2457 persons
      continuously enrolled for 11 years in a managed-care network were searched for
      International Classification of Diseases (ICD-9-CM) diagnoses of cataract, open
      angle glaucoma (OAG), nonexudative age-related macular degeneration (ARMD), and
      nonproliferative diabetic retinopathy (NPDR) at eye-care visits in the first half
      of 2001, the second half of 2010, and 2011. For each condition, incidence rates
      calculated by using "look-back" periods ranging from 0.5-9 years were compared
      with best estimates from a gold-standard period of 9.5 years. RESULTS: With a 1
      year disease-free look-back period, incidence was overestimated by 260% for
      cataract, 135% for OAG, 209% for ARMD, and 300% for NPDR. Expanding the disease
      free look-back period to 3 years resulted in a reduction of incidence
      overestimation to 40% for cataract, 14% for OAG, 45% for ARMD, and 100% for NPDR.
      A 5-year look-back period yielded incidence rates that were overestimated by <30%
      for all 4 conditions. CONCLUSIONS: In our claims-data analysis of 4 common ocular
      conditions, a disease-free interval <=1 year insufficiently distinguished newly
      diagnosed from pre-existing disease, resulting in grossly overestimated incidence
      rates. Using look-back periods of 3-5 years, depending on the specific diagnosis,
      yielded considerably more accurate estimates of disease incidence.

PMID- 23972307
TI  - Diagnostic fundus autofluorescence patterns in achromatopsia.
AB  - PURPOSE: To describe the unique diagnostic fundus autofluorescence (FAF) patterns
      in patients with achromatopsia and the associated findings on optical coherence
      tomography (OCT). DESIGN: Observational case series. METHODS: We evaluated 10
      patients with achromatopsia by means of best-corrected visual acuity (BCVA),
      ophthalmoscopy, Goldmann visual field, full-field electroretinography (ffERG),
      OCT, and FAF photography. FAF patterns were compared with patient age and foveal
      changes on OCT. RESULTS: Patients fell into two dichotomous age groups at the
      time of evaluation: six patients ranged from 11 to 23 years of age, and 3
      patients ranged from 52 to 63 years of age. All patients had severely reduced
      photopic ffERG responses, including those exhibiting preserved foveal structure
      on OCT. The younger patients had absent to mild foveal atrophy on OCT, and four
      of the six demonstrated foveal and parafoveal hyperfluorescence on FAF. In
      addition, a 7-month-old child with compound heterozygous mutations in CNGA3
      demonstrated similar foveal hyperfluorescence. The older patients demonstrated
      advanced foveal atrophy and punched-out foveal hypofluorescence with discrete
      borders on FAF imaging corresponding to the area of outer retinal cavitation on
      OCT. CONCLUSIONS: Foveal hyperfluorescence is an early sign of achromatopsia that
      can aid in clinical diagnosis. In our cohort, patients with achromatopsia
      demonstrated age-dependent changes in FAF, which are likely to be progressive and
      to correlate with foveal atrophy and cavitation on OCT. This finding may be
      useful in charting the natural course of the disease and in defining a
      therapeutic window for treatment.

PMID- 23972308
TI  - Risk factors, microbiological profile, and treatment outcomes of pediatric
      microbial keratitis in a tertiary care hospital in Hong Kong.
AB  - PURPOSE: To report the risk factors and microbiological profile of pediatric
      microbial keratitis cases in a tertiary care hospital in Hong Kong. DESIGN:
      Retrospective study. METHODS: Case records of patients <18 years old with
      microbial keratitis were reviewed over a period of 10 years, between January 2001
      and December 2010. Risk factors, microbiological profile, and treatment outcomes
      were analyzed. RESULTS: Overall, 18 patients (13 female, 5 male) with unilateral
      microbial keratitis were included. The mean age was 12.4 years (range: 3-17
      years). The most commonly associated risk factor was contact lens wear (15,
      83.3%). Seven cases (38.8%) were associated with orthokeratology lenses. Two
      cases (11.1%) were related to intrinsic keratopathy and 1 case (5.5%) was
      infected secondary to trauma. Microbiological culture was positive in 16 cases
      (88.8%). Overall, Pseudomonas sp. was the most commonly isolated organism (10/16,
      62.5%), followed by coagulase-negative Staphylococcus (5/16, 31.2%) and
      Corynebacterium sp. (2/16, 12.5%). All cases responded to intensive medical
      management with topical antibiotics. One case with posttraumatic keratitis
      required stepped surgeries with initial tectonic penetrating keratoplasty
      followed by lens aspiration and retinal detachment repair. At the last follow-up,
      13 out of 17 eyes (76.5%) had best-corrected visual acuity >=20/40. CONCLUSIONS:
      Contact lens wear was the most commonly encountered risk factor for the
      occurrence of microbial keratitis in the pediatric age group in our setting.
      Orthokeratology remains one of the leading causes of contact lens-related
      infections. The majority of the cases responded to medical management.).

PMID- 23972309
TI  - Mechanism of retinal pigment epithelium tear formation following intravitreal
      anti-vascular endothelial growth factor therapy revealed by spectral-domain
      optical coherence tomography.
AB  - PURPOSE: To demonstrate the mechanism by which retinal pigment epithelium (RPE)
      tears occur in eyes with neovascular age-related macular degeneration (AMD)
      treated with intravitreal anti-vascular endothelial growth factor (VEGF) agents
      using spectral-domain optical coherence tomography (OCT). DESIGN: Retrospective
      observational case series. METHODS: OCT images of 8 eyes that developed RPE tears
      following the administration of intravitreal anti-VEGF agents for neovascular AMD
      were evaluated. Pretear and posttear images were compared in order to elucidate
      the mechanism by which RPE tears occur in this setting. RESULTS: In all eyes,
      pretear images revealed a vascularized pigment epithelial detachment (PED)
      containing hyperreflective material consistent with choroidal neovascularization
      (CNV). This CNV was adherent to the undersurface of the RPE and created
      contractile folds in the RPE contour. In 6 eyes, contractile neovascular tissue
      spanned the PED, causing outward bowing of the Bruch membrane and a peaked
      appearance to the overlying RPE monolayer. RPE tears occurred after the first
      anti-VEGF injection in 6 of 8 eyes. The posttear OCT images showed a
      discontinuity in the RPE with the CNV adherent to the retracted RPE. In all eyes,
      the RPE ruptured along a segment of bare RPE not in contact with the CNV or Bruch
      membrane. CONCLUSIONS: Eyes with vascularized PEDs secondary to AMD may show
      specific OCT findings that increase the risk for RPE tear following intravitreal
      anti-VEGF injection. Rapid involution and contraction of neovascular tissue
      adherent to the undersurface of the RPE may impart a substantial contractile
      force that tears this already-strained tissue layer.

PMID- 23972310
TI  - Reduction of retinal sensitivity in eyes with reticular pseudodrusen.
AB  - PURPOSE: To evaluate the effect of macular reticular pseudodrusen on retinal
      function using multiple imaging methods. DESIGN: Prospective cross-sectional
      study. METHODS: Thirteen eyes with reticular pseudodrusen, but without any other
      macular abnormality or glaucoma, and 20 normal eyes were evaluated. All subjects
      underwent color fundus photography, infrared reflectance (IR), fundus
      autofluorescence (FAF), and microperimetry. RESULTS: The similarity in the number
      of reticular pseudodrusen was evaluated through inter-observer intraclass
      correlation coefficients, which ranged from 0.852-0.944. IR could detect
      reticular pseudodrusen within the center circle area in 12 eyes, whereas blue
      channel fundus photography and FAF could only detect these lesions in 1 and 3
      eyes, respectively. The number of reticular pseudodrusen correlated among the
      different imaging modalities (P < .001 for all) for all areas of the macula,
      except the center. The mean retinal sensitivity in eyes with reticular
      pseudodrusen was lower in all areas of the macula, compared with normal eyes (P <
      .001 for all). The number of reticular pseudodrusen correlated with retinal
      sensitivity in all areas by IR imaging (P = .003, P < .001, P = .003 for center,
      inner ring, outer ring, respectively), in the inner and outer rings by blue
      channel fundus photography (P < .001 for both), and in the inner and outer rings
      by FAF (P < .001 and P = .001, respectively). CONCLUSIONS: Although multiple
      imaging modalities are capable of quantifying reticular pseudodrusen, IR appears
      to have the best ability to do so as compared to blue-channel photography and
      FAF. The distribution and number of reticular pseudodrusen lesions are closely
      associated with retinal sensitivity.

PMID- 23972311
TI  - Transepithelial riboflavin/ultraviolet. a corneal cross-linking in keratoconus:
      morphologic studies on human corneas.
AB  - PURPOSE: To evaluate histologic and molecular changes in human keratoconic
      corneas after the procedure of transepithelial collagen cross-linking (CXL),
      without the removal of corneal epithelium. DESIGN: Experimental laboratory
      investigation. METHODS: Thirty corneal buttons were examined, 18 of which were
      from patients affected by severe keratoconus and submitted to penetrating
      keratoplasty (PK). Among these, 8 were analyzed without any treatment, 4 were
      treated with transepithelial CXL 2 hours before PK, and 6 were treated with
      transepithelial CXL 3 months before PK. Twelve normal corneal buttons from
      healthy donors were used as controls. The corneal buttons were then evaluated by
      hematoxylin-eosin staining and by immunostaining with markers of epithelial
      junction proteins (beta-catenin and connexin 43), of stromal keratocytes (CD34),
      of apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling
      [TUNEL] assay), and of collagen type I fibers. RESULTS: The analysis of
      epithelial markers showed a clear defective expression in keratoconic corneas
      before and soon after the transepithelial CXL treatment, returning to normal in
      corneas analyzed 3 months after transepithelial CXL. The analysis of stroma
      components indicated a loss of keratocytes in the upper stroma of keratoconic
      corneas and a trend toward a normal situation 3 months after transepithelial CXL;
      similarly, collagen fibers appeared disorganized in keratoconus, while their
      pattern appears to be close to normal 3 months after treatment. CONCLUSIONS:
      Histologic and immunohistochemical findings on human keratoconic corneas showed
      the presence of biochemical and morphologic alterations in the epithelium and the
      upper stroma that are significantly improved 3 months after transepithelial CXL.
      However, further studies are necessary to assess to what extent these results
      correlate with measurable biomechanical effects.

PMID- 23972312
TI  - Movement of internal canalicular orifice in association with blinking: direct
      observation after dacryocystorhinostomy.
AB  - PURPOSE: To examine movement of the internal canalicular orifice with blinking
      and lacrimal drainage under endonasal endoscopic observation after
      dacryocystorhinostomy. DESIGN: Observational anatomic study. METHODS: Twenty
      internal canalicular orifices (right 9, left 11) from 15 patients (age range: 44
      77 years) who underwent endoscopic endonasal dacryocystorhinostomy were
      prospectively examined. The patients sat on a chair with the chin projected
      slightly upward while digital images were taken. After examining the movement of
      the internal canalicular orifice with blinking, the patient's eye was stained
      with fluorescein dye, and diffusion from the orifice was examined with blinking.
      RESULTS: The internal canalicular orifice closed during eyelid opening, although
      always incompletely. In eyelid closing, the orifice opened, and was pulled
      laterally without folds. All 20 internal canalicular orifices formed a
      diverticulum. Three specimens illustrated the upper and lower canalicular ends
      emptying into the diverticulum. The closing of these canalicular ends was always
      incomplete. Movement of the internal canalicular orifice was slight during normal
      blinking, but forced blinking resulted in more movement. Movement of the lacrimal
      sac wall was slight. During the first few seconds without blinking, no
      fluorescein dye flowed from the orifice. After several blinks, fluorescein dye
      flowed out slowly from the orifice, and increased in volume with more blinking.
      The fluorescein dye traveled inferiorly by gravity. A forced blinking was related
      to more dye inflow. CONCLUSIONS: The internal canalicular orifice incompletely
      closed during eyelid opening, but this orifice largely opened during eyelid
      closing, with a slow gravitational inflow of lacrimal fluid.

PMID- 23972313
TI  - Intraocular pressure fluctuation during microincision vitrectomy with
      constellation vision system.
AB  - PURPOSE: To investigate intraocular pressure (IOP) fluctuation during various
      vitrectomy maneuvers using the vitrectomy system (Alcon Constellation Vision
      System). DESIGN: An experimental study as laboratory investigation. METHODS: In
      porcine eyes, 23- and 25-gauge vitrectomy was performed, and IOP fluctuations
      were evaluated in vitreous cutting mode, in aspiration mode, and during scleral
      compression. The measurements were performed with the IOP control setting turned
      on or off. RESULTS: Using the 23-gauge system with the IOP control setting turned
      on, IOP decreased from 30 to 23.7 mm Hg after starting vitreous cutting, and then
      returned to 30 mm Hg in 2.6 seconds. When the IOP control setting was turned off,
      IOP decreased to 19.1 mm Hg in 0.9 seconds, and remained at that pressure. Under
      aspiration at 650 mm Hg without cutting, IOP showed a sharp depression from 30 to
      12.2 mm Hg, and then returned to 30.6 mm Hg in 2.6 seconds with the IOP control
      setting turned on. When the IOP control setting was turned off, IOP decreased to
      2.2 mm Hg in 9.7 seconds, and did not recover. When the sclera was compressed
      without aspiration, IOP rapidly increased to 70-100 mm Hg, and then slowly
      decreased to 30 mm Hg in 3.5-4.0 seconds, with or without the IOP control system.
      Similar data were obtained with 25-gauge vitrectomy. CONCLUSIONS: The IOP control
      system can attenuate IOP fluctuations during vitrectomy maneuvers. There was no
      significant difference in IOP fluctuations between 23- and 25-gauge systems.

PMID- 23972314
TI  - Immunohistochemical features of lacrimal gland epithelial tumors.
AB  - PURPOSE: To investigate the immunohistochemical features of ocular adnexal
      pleomorphic adenoma and adenoid cystic carcinoma. DESIGN: Retrospective
      clinicopathologic study. METHODS: Clinical records and microscopic slides of 7
      cases of each tumor type were reviewed. Immunohistochemical probes for Ki-67 and
      p53, and newer nuclear markers MYB for adenoid cystic carcinoma and PLAG1 for
      pleomorphic adenoma, were employed. RESULTS: Pleomorphic adenomas were
      asymptomatic, whereas adenoid cystic carcinomas were painful. No pleomorphic
      adenomas recurred; 4 adenoid cystic carcinomas recurred, resulting in 3 deaths.
      Unusual histopathologic variants for which immunohistochemistry proved useful
      included a myoepithelioma, an atypical pleomorphic adenoma, tubular and
      solid/basaloid variants of adenoid cystic carcinoma, and a morphologically
      heterogeneous adenoid cystic carcinoma of a Wolfring gland. For the pleomorphic
      adenomas, the average Ki-67 proliferation index was 3.8%; p53 was weakly
      staining, with an average positivity of 18.5%; PLAG1 was strongly positive in all
      cases; MYB was negative in 5 cases and weakly focally positive in 2 cases. For
      the adenoid cystic carcinomas, the average Ki-67 proliferation index was 29.1%;
      p53 stained positively and strongly with an average of 39%; none stained
      positively for PLAG1; and 6 out of 7 were MYB positive. CONCLUSIONS: Between
      pleomorphic adenoma and adenoid cystic carcinoma, there was no overlap in Ki-67
      positivity. Positivity for p53 showed overlap in only one lesion of each type.
      PLAG1 and MYB positivity were highly discriminating between pleomorphic adenoma
      and adenoid cystic carcinoma. Immunohistochemical analysis should be investigated
      further for its role in the evaluation of pleomorphic adenoma and adenoid cystic
      carcinoma.

PMID- 23972315
TI  - Primary cervical spine carcinoid tumor in a woman with arm paresthesias and
      weakness: a case report.
AB  - INTRODUCTION: Carcinoid tumors are neuroendocrine neoplasms derived from the
      enterochromaffin cells. Central nervous system involvement is rare and has been
      reported either as metastases to the brain and spine or primary tumors involving
      the sacrococcygeal spine. We report the first case of a primary carcinoid tumor
      of the cervical spine. CASE PRESENTATION: A 50-year-old African-American woman
      presented with a 4-month history of numbness, paresthesias, and mild left-hand
      weakness. Magnetic resonance imaging of her cervical spine revealed a
      homogenously enhancing extradural mass, indenting the cervical cord and expanding
      the left neural foramen at C7-T1. A C7 corpectomy, en bloc resection of the
      tumor, and anterior C6-T1 fusion were performed to decompress the spinal cord and
      nerves and provide stability. Postoperative histopathologic examination and
      immunohistochemical analysis were consistent with carcinoid tumor. There has been
      no recurrence at the 6-year follow-up visit. CONCLUSIONS: Primary cervical
      carcinoid tumor is extremely rare, but should be included in the differential
      diagnosis of enhancing expansile extradural masses compressing the spinal cord
      and nerves. Surgical resection may provide a definitive cure.

PMID- 23972316
TI  - The microcirculation image quality score: development and preliminary evaluation
      of a proposed approach to grading quality of image acquisition for bedside
      videomicroscopy.
AB  - PURPOSE: Side-stream dark-field microscopy is currently used to directly
      visualize sublingual microcirculation at the bedside. Our experience has found
      inherent technical challenges in the image acquisition process. This article
      presents and assesses a quality assurance method to rate image acquisition
      quality before analysis. MATERIALS AND METHODS: We identified 6 common image
      capture and analysis problem areas in sublingual side-stream dark-field videos:
      illumination, duration, focus, content, stability, and pressure. We created the
      "Microcirculation Image Quality Score" by assigning a score of optimal (0
      points), suboptimal but acceptable (1 point), or unacceptable (10 points) to each
      category (for further details, go to http://www.MicroscanAnalysis.blogspot.com).
      We evaluated 59 videos from a convenience sample of 34 unselected, noncritically
      ill emergency department patients to create a test set. Two raters, blinded to
      each other, implemented the score. Any video with a cumulative score of 10 or
      higher (range, 0-60) was considered unacceptable for further analysis. RESULTS:
      We created the Microcirculation Image Quality Score and applied it to 59 videos.
      For this particular set of 59 videos, the mean (SD) passing quality score was
      1.68 (0.90), and the mean (SD) failing quality score was 15.74 (6.19), with 27 of
      59 passing the quality score less than 10. Highest failure occurred from pressure
      artifact. The interrater agreement for acceptability was assessed using Cohen
      kappa for each category: illumination (kappa = 1.0), duration (kappa = 1.0),
      focus (kappa = 0.91), content (kappa = 0.76), stability (kappa = 0.71), and
      pressure (kappa = 0.82) and overall pass-fail rates (score >10) (kappa = 0.66).
      CONCLUSION: Our Microcirculation Image Quality Score addresses many of the common
      areas where video quality can degrade. The criteria introduced are an objective
      way to assess the quality of image acquisition, with the goal of selecting videos
      of adequate quality for analysis. The interrater reliability results in our
      preliminary study suggest that the Microcirculation Image Quality Score is
      reasonably repeatable between reviewers. Further assessment is warranted.

PMID- 23972317
TI  - Michael william blackburn bradbury 1930-2013.

PMID- 23972318
TI  - Effect of fly ash on persistence, mobility and bio-efficacy of metribuzin and
      metsulfuron-methyl in crop fields.
AB  - Field evaluation of two fly ashes (40t/ha) on persistence, mobility and
      bioactivity of metribuzin and metsulfuron-methyl was studied in soybean and wheat
      crops, respectively. Metribuzin was applied as pre-emergence at 0.5kg/ha, while
      metsulfuron-methyl was applied post-emergence at 8g/ha. Results suggested that
      metribuzin in surface (0-15cm) soil of fly ash unamended plots reached below
      detectable limit in 60 days, while herbicide persisted till 112 days in surface
      soil of fly ash amended plots. No metribuzin leached down to subsurface (15-30cm)
      soil in fly ash amended plots, while traces of metribuzin (0.6-1.2MUg/kg) were
      recovered in subsurface soil of fly ash unamended plot. Metsulfuron-methyl in
      surface soil persisted till 15 days in control and 20 days in fly ash amended
      plots and no metsulfuron-methyl leached down to subsurface soil. Fly ash
      amendment had no adverse effect on the bioactivity of herbicides and yield of
      soybean and wheat. The study suggested that fly ash amendment to soil can be
      exploited to retain applied herbicides in surface soil. 

PMID- 23972319
TI  - Medical privacy after death: implications of new modifications to the health
      insurance portability and accountability act privacy rule.

PMID- 23972320
TI  - Effect of combination of montelukast and levocetirizine on otitis media with
      effusion: a prospective, placebo-controlled trial.
AB  - CONCLUSION: This study demonstrated that treatment with montelukast in
      combination with levocetirizine may have a beneficial effect on clinical
      improvement of middle ear fluid in children with otitis media with effusion
      (OME). OBJECTIVE: To evaluate the effect of the combination of montelukast and
      levocetirizine on shortening the duration of effusion in successfully treated OME
      in children. METHODS: This was a randomized, prospective, double-blind, placebo
      controlled trial. The study group consisted of 120 children (age range 2-6
      years), who were diagnosed with OME of at least 2 months duration. The children
      were randomized into one of four groups. The treatment packs containing
      montelukast 4 mg (tablet) and/or levocetirizine 2.5 mg/5 ml as the active drug or
      placebo were prepared, numbered, and distributed by the second author. RESULTS:
      The amelioration of bilateral otoscopic sign scores in the combination therapy
      group was statistically significantly greater than in all the other groups (p <
      0.05). Improvement in bilateral tympanometric findings in the combination therapy
      group and montelukast group was greater than in the other groups. However, this
      difference was not statistically significant (p > 0.05). When we compared the
      difference between otoscopic sign scores before and after treatment we found that
      it was statistically significant in every group (p > 0.05). However, the
      significant improvement in tympanometric findings occurred in all groups except
      the levocetirizine group (p > 0.05).

PMID- 23972321
TI  - Ocular manifestations of 22q11.2 microduplication.
AB  - PURPOSE: To report a new ocular manifestation of the dup22q11 syndrome and
      explore involved genes that may offer insight to mechanisms of pathogenesis.
      DESIGN: Case series. PARTICIPANTS: Two male patients with this syndrome diagnosed
      with dup22q11.2. METHODS: Medical records were reviewed. Duplication was detected
      in the oligo-single nucleotide polymorphism chromosomal microarray and duplicated
      genes within the segment where determined by literature and database review.
      Potential associations between the ophthalmologic manifestations and their
      physiopathology were investigated. MAIN OUTCOME MEASURES: Microarray results and
      identification of candidate genes within the duplicated segment. RESULTS: Our
      patients demonstrate previously unreported findings of dup22q11.2, including
      Marcus Gunn jaw winking, Duane's retraction syndrome, and other abnormal eye
      movements consistent with a congenital cranial dysinnervation disorder (CCDD),
      retinal vascular tortuosity, and primary infantile glaucoma. The duplicated
      segment in case 1 includes SNAP29, which could be linked with the development of
      retinal vascular tortuosity, and MAPK1, which seems to play a role in axonal
      development through the semaphorin pathway, which may serve as a candidate gene
      for CCDD. In case 2, the CLDN5 gene is within the duplicated segment. CLDN5 could
      be involved in the pathophysiology of glaucoma. CONCLUSIONS: Our cases expand the
      ocular phenotype for duplication of 22q11 and serve to identify potential
      candidate genes for the development of CCDD, retinal vascular tortuosity, and
      glaucoma.

PMID- 23972322
TI  - CFH and ARMS2 genetic polymorphisms predict response to antioxidants and zinc in
      patients with age-related macular degeneration.
AB  - OBJECTIVE: The Age-Related Eye Disease Study (AREDS) demonstrated that
      antioxidant and zinc supplementation decreases progression to advanced age
      related macular degeneration (AMD) in patients with moderate to severe disease.
      We evaluated the interaction of genetics and type of nutritional supplement on
      progression from moderate to advanced AMD. DESIGN: Genetic analysis of a
      randomized, prospective clinical trial. PARTICIPANTS: White patients with AREDS
      category 3 AMD in 1 eye and AREDS categories 1 through 4 AMD in the fellow eye
      enrolled in the AREDS with available peripheral blood-derived DNA (995). METHODS:
      Subjects were evaluated for known AMD genetic risk markers and treatment
      category. The progression rate to advanced AMD was analyzed by genotypes and
      AREDS treatment group using Cox regression. MAIN OUTCOME MEASURES: The effect of
      inherited gene polymorphisms on treatment group-specific rate of progression to
      advanced AMD. RESULTS: Over an average of 10.1 years, individuals with 1 or 2
      complement factor H (CFH) risk alleles derived maximum benefit from antioxidants
      alone. In these patients, the addition of zinc negated the benefits of
      antioxidants. Treatment with zinc and antioxidants was associated with a risk
      ratio (RR) of 1.83 with 2 CFH risk alleles (P = 1.03E-02), compared with outcomes
      for patients without CFH risk alleles. Patients with age-related maculopathy
      sensitivity 2 (ARMS2) risk alleles derived maximum benefit from zinc-containing
      regimens, with a deleterious response to antioxidants in the presence of ARMS2
      risk alleles. Treatment with antioxidants was associated with an RR of 2.58 for
      those with 1 ARMS2 risk allele and 3.96 for those with 2 ARMS2 risk alleles (P =
      1.04E-6), compared with patients with no ARMS2 risk alleles. Individuals
      homozygous for CFH and ARMS2 risk alleles derived no benefit from any category of
      AREDS treatment. CONCLUSIONS: Individuals with moderate AMD could benefit from
      pharmacogenomic selection of nutritional supplements. In this analysis, patients
      with no CFH risk alleles and with 1 or 2 ARMS2 risk alleles derived maximum
      benefit from zinc-only supplementation. Patients with one or two CFH risk alleles
      and no ARMS2 risk alleles derived maximum benefit from antioxidant-only
      supplementation; treatment with zinc was associated with increased progression to
      advanced AMD. These recommendations could lead to improved outcomes through
      genotype-directed therapy.

PMID- 23972323
TI  - Time trends in the levels and patterns of polycyclic aromatic hydrocarbons (PAHs)
      in pine bark, litter, and soil after a forest fire.
AB  - Forest fires are known as an important natural source of polycyclic aromatic
      hydrocarbons (PAHs), but time trends of PAH levels and patterns in various
      environmental compartments after forest fires have not been thoroughly studied
      yet. In this study, 16 US-EPA priority PAHs were analyzed for pine bark, litter,
      and soil samples collected one, three, five, and seven months after a forest fire
      in Pohang, South Korea. At the first sampling event, the highest levels of ?16
      PAHs were measured for the three types of samples (pine bark: 5,920 ng/g, litter:
      1,540 ng/g, and soil: 133 ng/g). Thereafter, there were apparent decreasing
      trends in PAH levels; the control samples showed the lowest levels (pine bark:
      124 ng/g, litter: 75 ng/g, and soil: 26 ng/g). The levels of PAHs in the litter
      and soil samples normalized by organic carbon (OC) fractions also showed
      decreasing trends, indicating a direct influence of the forest fire. Among the 16
      target PAHs, naphthalene was a dominant compound for all types of samples. Light
      PAHs with 2-4 rings significantly contributed to the total concentration, and
      their contribution decreased in the course of time. Runoff by heavy
      precipitation, evaporation, and degradation of PAHs in the summer were probably
      the main reasons for the observed time trends. The results of principal component
      analysis (PCA) and diagnostic ratio also supported that the forest fire was
      indeed an important source of PAHs in the study area.

PMID- 23972324
TI  - Climate change and waterborne diarrhoea in northern India: impacts and adaptation
      strategies.
AB  - Although several studies show the vulnerability of human health to climate
      change, a clear comprehensive quantification of the increased health risks
      attributable to climate change is lacking. Even more complicated are assessments
      of adaptation measures for this sector. We discuss the impact of climate change
      on diarrhoea as a representative of a waterborne infectious disease affecting
      human health in the Ganges basin of northern India. A conceptual framework is
      presented for climate exposure response relationships based on studies from
      different countries, as empirical studies and appropriate epidemiological data
      sets for India are lacking. Four climate variables are included: temperature,
      increased/extreme precipitation, decreased precipitation/droughts and relative
      humidity. Applying the conceptual framework to the latest regional climate
      projections for northern India shows increases between present and future
      (2040s), varying spatially from no change to an increase of 21% in diarrhoea
      incidences, with 13.1% increase on average for the Ganges basin. We discuss three
      types of measures against diarrhoeal disease: reactive actions, preventive
      actions and national policy options. Preventive actions have the potential to
      counterbalance this expected increase. However, given the limited progress in
      reducing incidences over the past decade consorted actions and effective
      implementation and integration of existing policies are needed. 

PMID- 23972325
TI  - Assessment of trace pollutants in Korean coastal sediments using the triad
      approach: a review.
AB  - Here we summarize and review the previous efforts on sediment assessment together
      with major scientific findings that were conducted in the Korean coastal waters
      since late 1990s. Towards integrated triad analysis, sediment data (>1700
      samples) reported from the Korean coasts were collected and reviewed of which
      data collectively includes three components of chemical, toxicological, and
      ecological measures. First, the chemistry data suggested widespread and historic
      distribution of sedimentary pollutants along the Korean coasts. Spatial
      distributions suggested that their sources were independent of each other, while
      some localized areas (highlighted for Lake Shihwa, Masan Bay, and Ulsan Bay) and
      zones with extremely high pressures of certain pollutants were also identified.
      The mass balance analyses and/or direct correlations linking triad components
      reflected a general agreement between endpoints. The benthic community responses
      given by species occurrence and diversity also reflected the type and degree of
      sediment contamination, however, could not be fully explained by the known target
      chemicals. Overall, the triad assessment of trace pollutants in Korean coastal
      sediments seemed to be useful and much powerful when all the components are fully
      addressed. 

PMID- 23972326
TI  - Esterification of sodium 4-hydroxybenzoate by ultrasound-assisted solid-liquid
      phase-transfer catalysis using dual-site phase-transfer catalyst.
AB  - The catalytic esterification of sodium 4-hydroxybenzoate with benzyl bromide by
      ultrasound-assisted solid-liquid phase-transfer catalysis (U-SLPTC) was
      investigated using the novel dual-site phase-transfer catalyst 4,4'
      bis(tributylammoniomethyl)-1,1'-biphenyl dichloride (BTBAMBC), which was
      synthesized from the reaction of 4,4'-bis(chloromethyl)-1,1'-biphenyl and
      tributylamine. Without catalyst and in the absence of water, the product yield at
      60  degrees C was only 0.36% in 30 min of reaction even under ultrasound
      irradiation (28 kHz/300 W) and 250 rpm of stirring speed. When 1cm(3) of water
      and 0.5 mmol of BTBAMBC were added, the yield increased to 84.3%. The catalytic
      intermediate 4,4'-bis(tributylammoniomethyl)-1,1'-biphenyl di-4-hydroxybenzoate
      was also synthesized to verify the intrinsic reaction which was mainly conducted
      in the quasi-aqueous phase locating between solid and organic phases. Pseudo
      first-order kinetic equation was used to correlate the overall reaction, and the
      apparent rate coefficient with ultrasound (28 kHz/300 W) was 0.1057 min(-1), with
      88% higher than that (0.0563 min(-1)) without ultrasound. The esterification
      under ultrasonic irradiation using BTBAMBC by solid-liquid phase-transfer
      catalysis was developed.

PMID- 23972327
TI  - Dispersion of nanoparticles: from organic solvents to polymer solutions.
AB  - This work is devoted to a systematic study of nanoparticle dispersion by
      ultrasonication in different solutions: from organic solvents to polymer
      solutions. The cluster size of nanoparticles at different concentrations in both
      organic solvents and polymer solutions were directly characterized by Dynamic
      Light Scattering to study the effect of solid concentration, surfactant and
      polymer on the dispersion. It reveals that in stabilized suspensions, the
      smallest attainable size or aggregate size of nanoparticles is independent of
      solvent type and solid content over the tested range. Furthermore, nanoparticles
      in simple solvent and in polymer solutions had the similar evolution of cluster
      size and almost the same final size, which could be very helpful to optimize the
      dispersion of nanofillers in polymer solutions and nanocomposites. It is also
      shown that, with appropriate sonication amplitudes, the dispersion procedure
      developed for very dilute suspensions could be transferred to higher
      concentration suspensions or even to polymer suspensions. 

PMID- 23972328
TI  - Calcineurin expression and localisation during porcine oocyte growth and meiotic
      maturation.
AB  - The processes of oocyte growth, acquisition of meiotic competence and meiotic
      maturation are regulated by a large number of molecules. One of them could be
      calcineurin consisting of catalytic subunit A (Aalpha, Abeta, Agamma isoforms)
      and regulatory subunit B (B1, B2 isoforms). Calcineurin is involved in the
      meiotic maturation of oocytes in invertebrates or in lower vertebrates. In the
      mammalian oocytes, the possible role of calcineurin in the regulation of oocyte
      meiosis has not been clarified to date. In this study, to investigate the role of
      calcineurin during porcine oocyte growth, acquisition of meiotic competence and
      meiotic maturation, we analysed the expression and localisation of calcineurin
      subunits and the mRNA expression of calcineurin isoforms. Calcineurin was
      expressed in growing porcine oocytes, in fully grown oocytes and during their in
      vitro meiotic maturation. We found both subunits of calcineurin. Calcineurin A
      and calcineurin B were localised mainly in the cortex in all porcine oocytes. The
      changes in the intracellular localisation of separate calcineurin subunits during
      meiotic maturation were determined. We detected mRNA for calcineurin isoforms
      Abeta, Agamma, B2 in oocytes and mRNA for calcineurin isoforms Abeta, Agamma, B1,
      and B2 in cumular cells. To our knowledge, this is the first confirmation of
      calcineurin presence in porcine oocytes. 

PMID- 23972329
TI  - Evaluation of implementation of the ParkFit program: A multifaceted intervention
      aimed to promote physical activity in patients with Parkinson's disease.
AB  - OBJECTIVES: We recently completed the ParkFit study, a two-year randomized
      controlled trial including 586 sedentary Parkinson's disease (PD) patients, that
      evaluated a multifaceted intervention (ParkFit program) to promote physical
      activity. The results showed that the ParkFit program enables PD patients to
      become physically more active, suggesting that this intervention should now be
      further implemented into clinical practice. To facilitate this process, we here
      evaluate the implementation of the ParkFit program. METHODS: The ParkFit program
      was evaluated in three ways: (a) experiences of patients and physiotherapists, as
      investigated using interviews and questionnaires; (b) factors associated with
      changed activity levels; and (c) subgroup analyses to identify differential
      effects in subgroups of patients based on baseline physical activity level, age,
      gender, disease severity, disease duration, and mobility. RESULTS: The ParkFit
      program was well received: 73% of patients indicated they would recommend the
      program to other patients, and 90% of physiotherapists indicated they wanted to
      use the ParkFit program in other patients. Multiple forward regression analysis
      resulted in a model with two variables: less baseline physical activity, and
      better mobility were associated with larger changes in levels of physical
      activity (R(2)=38%). The program was effective in almost all subgroups. In women,
      most sedentary patients and patients with higher disease severity, the estimated
      effect size was largest. CONCLUSION: We conclude that the ParkFit program was
      effective in almost all specific subgroups. Therapists and patients experienced
      no major hurdles. Suggestions for improvement are: (1) improve education for
      therapists with respect to theories about behavioral change; (2) formulate
      concrete and specific examples of exercise goals; and (3) pay more specific
      attention to patients with co morbidities, cognitive dysfunction and a lack of
      motivation during education.

PMID- 23972330
TI  - Early predictors of outcomes in pediatric lupus nephritis: focus on proliferative
      lesions.
AB  - OBJECTIVES: Studies regarding the clinical features and outcomes of pediatric
      lupus nephritis are limited, and risk factors of poor outcome in the more severe
      form of renal involvement, proliferative lupus nephritis (PLN), are poorly
      understood. This study analyzed the data from a large prospective cohort of
      childhood systemic lupus erythematosus to determine such risk factors. METHODS:
      Subjects younger than 18 years at onset with biopsy-proven lupus nephritis were
      enrolled. Data on baseline presentations and laboratory values, response to
      treatment, and outcomes were collected. Primary outcome measures were death or
      end-stage renal disease (ESRD). Survival analysis was done and predictors were
      approached. RESULTS: One hundred four patients with mean age of 12.4 +/- 2.5
      years (range, 4.0-17.2 years) and the female-to-male ratio of 5.94:1 were
      included. Among them, 81 patients had PLN and 23 had non-proliferative lupus
      nephritis. Those with PLN had significantly lower GFR, more proteinuria, more
      urine sediment, more hypertension, and poor early response to treatment (within 6
      months). There was no significant difference in extra-renal manifestations. All
      poor outcomes happened in the PLN group. The prognostic factors were high
      baseline SLEDAI-2k >20 (HR, 6.76; p = 0.002), baseline GFR <60ml/min/m2 (HR,
      3.88; p = 0.022), and early responder (HR, 0.19; p = 0.013). CONCLUSIONS:
      Patients with pediatric lupus nephritis and high risk factor can be identified
      early by concomitantly considering their baseline features and early response,
      which provides a novel hint in decision for management decisions.

PMID- 23972331
TI  - Computer simulation of cardiac cryoablation: comparison with in vivo data.
AB  - Simulation of cardiac cryoablation by the finite element method can contribute to
      optimizing ablation results and understanding the effects of modifications prior
      to time-consuming and expensive experiments. In this work an intervention
      scenario using a 9 Fr 8 mm tip applicator applied to ventricular tissue was
      simulated using the effective heat capacity model based on Pennes' bioheat
      equation. Using experimentally obtained refrigerant flow rates and temperature
      profiles recorded by a thermocouple located at the tip of the applicator the
      cooling performance of the refrigerant was estimated and integrated by time and
      temperature dependent boundary conditions based on distinct phases of a freeze
      thaw cycle. Our simulations exhibited a mean difference of approximately 6
      degrees C at the applicator tip compared to temperature profiles obtained during
      in vivo experiments. The presented model is a useful tool for simulation and
      validation of new developments in clinical cardiac cryoablation.

PMID- 23972332
TI  - Automatic detection of drowsiness in EEG records based on multimodal analysis.
AB  - Drowsiness is one of the main causal factors in many traffic accidents due to the
      clear decline in the attention and recognition of danger drivers, diminishing
      vehicle-handling abilities. The aim of this research is to develop an automatic
      method to detect the drowsiness stage in EEG records using time, spectral and
      wavelet analysis. A total of 19 features were computed from only one EEG channel
      to differentiate the alertness and drowsiness stages. After a selection process
      based on lambda of Wilks criterion, 7 parameters were chosen to feed a Neural
      Network classifier. Eighteen EEG records were analyzed. The method gets 87.4% and
      83.6% of alertness and drowsiness correct detections rates, respectively. The
      results obtained indicate that the parameters can differentiate both stages. The
      features are easy to calculate and can be obtained in real time. Those variables
      could be used in an automatic drowsiness detection system in vehicles, thereby
      decreasing the rate of accidents caused by sleepiness of the driver. 

PMID- 23972333
TI  - Has the prevalence of health care services use increased over the last decade
      (2001-2009) in elderly people? A Spanish population-based survey.
AB  - OBJECTIVES: (1) To describe the prevalence of general practitioner visits and
      hospitalization according to sex and age groups; (2) to identify which factors
      are independently associated with a higher use of health care services among
      elderly Spanish; and (3) to study the time trends in the prevalence of use of
      health care services 2001-2009. STUDY DESIGN: Observational study. We analyzed
      data from the Spanish National Health Surveys conducted in 2001 (n=21,058), 2003
      (n=21,650), 2006 (n=29,478) and 2009 (n=22,188). We included responses from
      adults aged 65 years and older. OUTCOME MEASURES: The main variables were the
      number of general practitioner visits in the last 4 weeks and hospitalization in
      the past year. We stratified the adjusted models by the main variables. We
      analyzed socio-demographic characteristics, health related variables, using
      multivariate logistic regression models. RESULTS: The total number of subjects
      was 24,349 (15,041 woman, 9309 men). Women were significantly older than men
      (P<0.001). Women had higher prevalence of general practitioner visits than men in
      all surveys. Men had significantly higher prevalence of hospitalizations than
      women in the years 2001, 2006 and 2009. When we adjusted the hospitalization by
      possible confounders using logistic regressions, men had a higher probability of
      being hospitalized than women (OR 1.53, 1.39-1.69). The variables that were
      significantly associated with a higher use of health care services were lower
      educational level, worse self-rated health, chronic conditions, polypharmacy, and
      the level of disability. The number of general practitioner visits among women
      and men significantly increased from 2001 to 2009 (women: OR 1.43, 1.27-1.61;
      men: OR 1.71, 1.49-1.97). CONCLUSIONS: The current study revealed an increase in
      health care services utilization from 2001 to 2009 in the older Spanish
      population.

PMID- 23972334
TI  - The adolescent with asthma.
AB  - The adolescent with asthma experiences a period of physical and psychosocial
      changes that affect their health and well-being. Overall, adolescents with asthma
      are at increased risk for asthma morbidity and death. Increased rates of
      depression and anxiety, for the adolescent and their caregivers, can lead to non
      adherence to their medical regimens, poor symptom control, and poor treatment
      outcomes. Contextual factors, such as race, ethnicity, and living situation,
      affect the prevalence, morbidity, and mortality for the adolescent with asthma.
      These factors also affect the transition process for adolescents entering adult
      medical care. An overview is presented of how the adolescent with asthma differs
      and how healthcare providers can promote effective asthma management and better
      asthma control. 

PMID- 23972335
TI  - Phenylphenalenones and oxabenzochrysenones from the Australian plant Haemodorum
      simulans.
AB  - Chemical investigation of the Australian plant Haemodorum simulans
      (Haemodoraceae) resulted in the isolation of two new phenylphenalenones,
      haemoxiphidone and haemodordioxolane from the bulbs together with the first
      report of an oxabenzochrysenone glycoside, haemodoroxychrysenose from the aerial
      parts of the plant. Also isolated were two previously described
      phenylphenalenones 5,6-dimethoxy-7-phenyl-1H,3H-naphtho[1,8-cd]pyran-1,3-dione
      and haemodorone and two oxabenzochrysenones 5-hydroxyl-2-methoxy-1H-naphtho[2,1,8
      mna]xanthen-1-one and 5-methoxy-1H-naphtho[2,1,8-mna]xanthen-1-one. The X-ray
      structure of the phenylphenalenone 5,6-dimethoxy-7-phenyl-1H,3H-naphtho[1,8
      cd]pyran-1,3-dione was secured for the first time. All compounds were deduced by
      detailed spectroscopic analyses. HPLC-NMR chemical profiling of an enriched
      fraction containing a mixture of haemodordioxolane and 5,6-dimethoxy-7-phenyl
      1H,3H-naphtho[1,8-cd]pyran-1,3-dione facilitated the partial identification of
      these secondary metabolites. The structure previously assigned as xiphidone in
      our initial studies of this plant was re-assigned as the new isomer
      haemoxiphidone. 

PMID- 23972336
TI  - Management of complex glottic stenosis in children with recurrent respiratory
      papillomatosis.
AB  - OBJECTIVES: To describe our management of complex glottic stenosis in tracheotomy
      dependent children with severe recurrent respiratory papillomatosis. METHODS:
      Retrospective chart review at a tertiary care children's hospital. RESULTS: Three
      children with complex glottic stenosis secondary to severe recurrent respiratory
      papillomatosis were treated at our institution since 2011. Two patients had
      complete stenosis, and the third had near-complete stenosis. Two patients were
      managed using balloon dilation alone, and the third also underwent
      laryngotracheal reconstruction with posterior costal cartilage grafting. Two
      patients have been successfully decannulated and the third has been tolerating
      continuous tracheotomy capping for greater than twelve months. All three patients
      underwent aggressive debridement of papillomatosis and balloon dilation every 4-6
      weeks until their burden of disease was controlled. In two patients, the glottic
      airway was patent, and the third continued to have complete restenosis between
      procedures and required laryngotracheoplasty with multiple post-operative
      dilation procedures to establish an adequate glottic airway. CONCLUSIONS: Severe
      laryngeal stenosis is a well-described complication of recurrent respiratory
      papillomatosis, but its management is not well-defined. Aggressive management of
      papillomatosis with frequent debridement is critical in successfully managing
      laryngeal stenosis. Balloon dilation alone may be surprisingly effective in these
      patients, and laryngotracheoplasty can be used as an adjunct procedure in those
      patients who fail balloon dilation. Given the quality of life issues and concerns
      regarding distal spread of disease with tracheotomies in these patients, we feel
      that aggressive management and early decannulation is in the patient's best
      interest.

PMID- 23972337
TI  - Simple technique for transferring the contour of the skin defect from the
      recipient site to the donor site when harvesting full thickness skin grafts in
      the head and neck.

PMID- 23972338
TI  - Obesity and female stress urinary incontinence.
AB  - The purpose of this article was to review the epidemiology, pathophysiology, and
      treatment options for stress urinary incontinence in the obese female patient and
      draw conclusions regarding the optimal treatment of this condition in this unique
      patient population. Obesity results in increased intra-abdominal pressure and
      this leads to weakening of the pelvic floor innervation and musculature. Weight
      loss through lifestyle modification and bariatric surgery improves stress urinary
      incontinence. Success of stress urinary incontinence surgery in obese women is
      similar to nonobese patients. Obese women should not be excluded from potentially
      curative surgery based on their body mass index (BMI) alone. 

PMID- 23972339
TI  - Salvage radiotherapy after robot-assisted laparoscopic radical prostatectomy.
AB  - OBJECTIVE: To assess the incidence and efficacy of salvage radiotherapy (SRT)
      after robot-assisted radical prostatectomy (RARP). RARP has been linked to an
      increased use of adjuvant treatments. If RARP would result in an increased local
      recurrence rate, response rates to SRT could be expected to be better after RARP
      than after more conventional methods of prostatectomy. The incidence and efficacy
      of SRT in a RARP population were compared with nomogram prediction. METHODS:
      Patient data were prospectively registered. Biochemical recurrence (BCR) was
      defined as a prostate-specific antigen (PSA) >=0.1 ng/mL. SRT was offered to men
      with BCR after RARP. The Stephenson nomogram predictions were compared with
      outcome after SRT. RESULTS: Of 1087 men, 157 (14.4%) received SRT for BCR or
      persistent PSA levels during a median follow-up of 1078 days after RARP. Median
      PSA level before SRT was 0.2 ng/mL. Three-year BCR-free rate was 64% for men
      after SRT. pN (pNx, pN0, pN1) and PSA level before SRT were independent
      predictors of the BCR interval after SRT. Men with more extensive fascia
      preservation were more likely to respond favorably to SRT. The Stephenson
      nomogram prediction showed a concordance rate of 0.66 in this RARP population.
      Limitations of the study are the retrospective design and limited follow-up
      duration. CONCLUSION: In our RARP series, the use and efficacy of SRT were
      comparable with open prostatectomy series. The Stephenson nomogram reliably
      predicted outcome in patients with RARP with SRT, suggesting that similar
      characteristics predict response to SRT after RARP compared with open
      prostatectomy.

PMID- 23972340
TI  - Editorial comment.

PMID- 23972342
TI  - Incidental capture of rarely diagnosed pediatric tumor: an infant boy with clear
      cell sarcoma of the kidney.
AB  - Clear cell sarcoma of the kidney (CCSK) is an uncommon neoplasm that accounts for
      less than 5% of all pediatric renal tumors. Compared with Wilms' tumor, CCSK has
      a higher rate of relapse, greater propensity for bone metastasis, and poorer
      overall survival. We present the case of a 19-month-old boy with a large renal
      mass diagnosed incidentally by ultrasonography during surveillance for
      vesicoureteral reflux. This report describes the rare occurrence of an incidental
      radiologic capture of CCSK and provides a brief review of disease pathology. 

PMID- 23972343
TI  - Correlation of QT interval correction methods during atrial fibrillation and
      sinus rhythm.
AB  - The calculation of the corrected QT interval (QTc) is particularly problematic in
      patients during atrial fibrillation (AF). The aims of this study were to compare
      the QTc calculated using Bazett's formula in AF and sinus rhythm (SR) and
      determine whether alternative methods for QT correction were superior to
      Bazett's, in an effort to define the optimal method for QT correction in patients
      with AF. We evaluated consecutive patients with persistent AF admitted for
      initiation of dofetilide. The QT interval was corrected according to the
      following formulas: Bazett's, Fridericia, and Framingham. We compared the QTc
      interval on the last electrocardiogram in AF to the first electrocardiogram in
      SR. The cohort included 54 patients (age 60 +/- 10 years, 80% men) with
      persistent AF for a median of 36 months. Bazett's overestimated QTc during AF
      compared with SR (464 +/- 34 vs 445 +/- 38 ms, p = 0.008); in contrast,
      Framingham underestimated it (385 +/- 48 vs 431 +/- 40 ms, p <0.001,
      respectively). However, there was no significant difference between the QTc
      interval in AF and SR when assessed by Fridericia (435 +/- 33 vs 440 +/- 35 ms, p
      = 0.46). There were 24 dofetilide dose reductions based on Bazett's QTc; this
      would have been avoided in 33% of patients had Fridericia been used. In
      conclusion, the commonly used Bazett's formula leads to an overestimation of the
      QTc during AF. This may result in unnecessary reduction in antiarrhythmic doses
      and thus drug efficacy. These data suggest that the Fridericia most closely
      approximates the QTc during AF to QTc during SR.

PMID- 23972344
TI  - Outcomes of consecutive patients referred for consideration for transcatheter
      aortic valve implantation from an encompassing health-care region.
AB  - Procedural outcomes for transcatheter aortic valve implantation (TAVI) are well
      described. However, limited information exists regarding patient screening and
      selection. Thus, the purpose of the study was to review consecutive patients
      referred for TAVI from an inclusive-defined population. The Mazankowski Alberta
      Heart Institute TAVI program has maintained a prospective database on all
      referred patients. Patients are reviewed in outpatient clinic attended by a
      nurse, cardiologist, cardiac surgeon, and administrative assistant. After workup
      is complete, a TAVI Heart Team conference occurs to accept or reject each
      patient. Since November 2009, 276 patients (145 men and 131 women) have been
      referred with a steady increase in the number of referrals annually. Mean age was
      82.2 years (men 81.6 and women 82.8), with 13% aged <70 years. Mean EuroSCORE was
      13.8 and mean STS score was 5.7. Of the referred patients, 34% received TAVI, 17%
      were rejected, 12% underwent open AVR, 10% refused TAVI, and 27% are currently
      being assessed or followed. There were no differences in the mean EuroSCORE (13.4
      vs 14.3; p = 0.64) or STS scores (5.2 vs 6.4; p = 0.13) of those accepted for
      TAVI versus those who were not. In conclusion, a team-based approach to assess
      this complex patient population is essential to ensure efficient and
      comprehensive evaluation, in turn determining appropriate care allocation. With
      expansion of clinical experience and the evidence supporting TAVI, the Heart
      Teams defined to assess this patient population will be burdened with increased
      clinical commitment and require appropriate support.

PMID- 23972345
TI  - Frequency and prognostic significance of hemoptysis in pediatric pulmonary
      arterial hypertension.
AB  - Data concerning the prevalence, risk factors, and prognostic significance of
      hemoptysis in pediatric pulmonary arterial hypertension (PAH) are scarce. A Dutch
      national cohort of 74 children with either idiopathic or heritable PAH
      (IPAH/HPAH, n = 43) or PAH associated with congenital heart disease (PAH-CHD, n =
      31) were followed from 1993 to 2012. During a median follow-up of 3.5 years
      (range 0.1 to 19.2), hemoptysis occurred in 13 children (17.6%). The hemoptysis
      event rate was 9.9 per 100 patient-years, equally divided between IPAH/HPAH and
      PAH-CHD (p = 0.824). The median age at first hemoptysis was 12.5 years, and the
      median time since PAH diagnosis to first hemoptysis was 6.1 years. Patients with
      hemoptysis had longer time since PAH diagnosis (p = 0.001) and more frequently
      used anticoagulant therapy (p = 0.006). Univariate Cox regression analysis
      indicated that older age (hazard ratio [HR] 1.15, 95% confidence interval [CI]
      1.01 to 1.30, p = 0.031), World Health Organization functional class IV (HR 0.28,
      95% CI 0.08 to 0.95, p = 0.042), higher mean pulmonary arterial pressure (HR
      1.04, 95% CI 1.00 to 1.07, p = 0.028), and higher indexed pulmonary vascular
      resistance (HR 1.08, 95% CI 1.02 to 1.15, p = 0.009), all at the time of PAH
      diagnosis, were associated with increased risk of hemoptysis during follow-up.
      Ten of 13 patients with hemoptysis died or underwent (heart-) lung
      transplantation; in 6 patients, this was directly related to hemoptysis. In
      conclusion, the occurrence of hemoptysis in pediatric IPAH/HPAH and PAH-CHD
      increases with time since diagnosis, is a serious condition, and is, in case of
      life-threatening hemoptysis, associated with poor outcome.

PMID- 23972346
TI  - Comparison of mortality in women versus men with infections involving
      cardiovascular implantable electronic device.
AB  - Device infection is a complication of implantable cardioverter-defibrillator
      (ICD) therapy that significantly increases mortality. Risk factors associated
      with death and ICD infection are poorly understood. The purpose of this study was
      to identify patient characteristics associated with death after cardiovascular
      implantable electronic device (CIED) infection. This is a retrospective cohort
      study of 64,903 Medicare fee-for-service patients who received an ICD in 2007,
      including 1,855 with device infection. Long-term survival was significantly
      reduced with CIED infection (71.6% vs 85.0%, p <0.001). Regression analysis
      accounting for age, race, gender, and 28 co-morbidities identified only 2 patient
      characteristics associated with decreased long-term survival with CIED infection:
      female gender and human immunodeficiency virus/acquired immunodeficiency
      syndrome. In patients with CIED infection, women had substantially reduced long
      term survival compared with men (67.3% vs 72.9%, p <0.02). The risk-adjusted
      hazard ratio for long-term mortality with device infection in women compared with
      that in men increased significantly from 0.86 (95% confidence interval [CI] 0.82
      to 0.91) to 1.25 (95% CI 1.02 to 1.53), corresponding to a risk increase of >45%.
      Importantly, a substantial portion of this excess mortality occurred after the
      index admission for infection, when the hazard ratio for death in women compared
      with that in men increased from 0.86 (95% CI 0.82 to 0.91) to 1.20 (95% CI 0.96
      to 1.51) with CIED infection, despite little gender difference in admission
      length of stay, disposition, and cost. In conclusion, women are significantly
      more likely than men to die with CIED infection. A substantial part of this
      excess mortality occurs after discharge. It will be important to identify and
      address the cause(s) of this gender difference in mortality.

PMID- 23972347
TI  - Predictors of regional variations in hospitalizations following emergency
      department visits for atrial fibrillation.
AB  - The emergency department (ED) is often where atrial fibrillation (AF) is first
      detected and acutely treated and affected patients dispositioned. We used the
      Nationwide Emergency Department Sample to estimate the percentage of visits
      resulting in hospitalization and investigate associations between patient and
      hospital characteristics with hospitalization at the national and regional
      levels. We conducted a cross-sectional study of adults with AF listed as the
      primary ED diagnosis in the 2007 to 2009 Nationwide Emergency Department Sample.
      We performed multivariate logistic regression analyses investigating the
      associations between prespecified patient and hospital characteristics with
      hospitalization. From 2007 to 2009, there were 1,320,123 weighted ED visits for
      AF, with 69% hospitalized nationally. Mean regional hospitalization proportions
      were: Northeast (74%), Midwest (68%), South (74%), and West (57%). The highest
      odds ratios for predicting hospitalization were heart failure (3.85, 95%
      confidence interval [CI] 3.66 to 4.02), chronic obstructive pulmonary disease
      (2.47, 95% CI 2.34 to 2.61), and coronary artery disease (1.65, 95% CI 1.58 to
      1.73). After adjusting for age, privately insured (0.77, 95% CI 0.73 to 0.81) and
      self-pay (0.77 95% CI 0.66 to 0.90) patients had lower odds compared with
      Medicare recipients, whereas Medicaid (1.21, 95% CI 1.11 to 1.32) patients tended
      to have higher odds. Patients living in low-income zip codes (1.18, 95% CI 1.12
      to 1.25) and patients treated at large metropolitan hospitals (1.75, 95% CI 1.59
      to 1.93) had higher odds. In conclusion, our analysis showed considerable
      regional variation in the management of patients with AF in the ED and in
      associations between patient socioeconomic and hospital characteristics with ED
      disposition; adapting best practices from among these variations in management
      could reduce hospitalizations and health-care expenses. 

PMID- 23972348
TI  - Comparison of cancer risk associated with low-dose ionizing radiation from
      cardiac imaging and therapeutic procedures after acute myocardial infarction in
      women versus men.
AB  - Patients with cardiovascular disease are increasingly exposed to low-dose
      ionizing radiation (LDIR) from diagnostic and therapeutic procedures. Previous
      studies have suggested that the malignancy risk associated with LDIR may be
      greatest in women and in young patients. We sought to compare the effect of LDIR
      on incident cancer across gender and age strata in a population-based cohort of
      patients with myocardial infarction (MI). All initially cancer-free patients with
      MI from 1996 to 2006 were identified in a province-wide administrative database.
      Procedure-specific LDIR dose estimates were used to generate a cumulative cardiac
      LDIR exposure variable. Time-dependent multivariate Cox regression was used to
      determine the relation between cardiac LDIR and incident cancer. A time-lag
      covariate of 3 years was used wherein a de novo cancer could only be attributed
      to LDIR incurred at least 3 years earlier. The effect of age and gender on LDIR
      associated risk of cancer was evaluated with stratified models and the addition
      of interaction terms. The study cohort consisted of 56,606 men and 26,255 women.
      For each millisievert of cardiac LDIR, women were more likely to develop a cancer
      (hazard ratio 1.005, 95% confidence interval 1.002 to 1.008) than men (hazard
      ratio 1.002, 95% confidence interval 1.001 to 1.004) after adjusting for age,
      noncardiac LDIR, and covariates (p for interaction = 0.014). Contrarily, over the
      range studied (predominantly patients aged >50 years), age was not a determinant
      of LDIR-associated risk of cancer. In conclusion, women exposed to LDIR from
      cardiac imaging and therapeutic procedures after MI are at a greater risk of
      incident cancer compared with men after similar exposure. The extrapolated
      absolute risk from LDIR exposure would nonetheless be expected to be low.

PMID- 23972349
TI  - Antiplatelet effect of thienopyridine (clopidogrel or prasugrel) pretreatment in
      patients undergoing primary percutaneous intervention for ST elevation myocardial
      infarction.
AB  - Although previous retrospective studies have suggested the clinical benefits of
      clopidogrel pretreatment in patients with ST-segment elevation myocardial
      infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI),
      the antiplatelet effect of thienopyridines during a narrow door-to-balloon time
      frame has not been evaluated. Seventy-nine consecutive patients with STEMI were
      treated with either 600 mg of clopidogrel (n = 49) or 60 mg of prasugrel (n = 30)
      loading on admission. All patients underwent PPCI with a door-to-balloon time of
      48 +/- 20 minutes. Adenosine diphosphate (ADP)-induced platelet aggregation (PA)
      was determined by light transmission aggregometry before thienopyridine loading,
      at PPCI, and after 72 hours. Baseline ADP-induced PA was comparable in
      clopidogrel- and prasugrel-treated patients (79 +/- 10% vs 76 +/- 9%, p = 0.2).
      Although ADP-induced PA was reduced significantly in both clopidogrel- and
      prasugrel-treated patients (p <0.01 for both), it was significantly lesser in
      prasugrel-treated patients (63 +/- 18% vs 74 +/- 12%, p = 0.002). Yet, <50% of
      the prasugrel-treated patients achieved adequate platelet inhibition (ADP-induced
      PA <70%) at PPCI. Prasugrel-treated patients, compared with clopidogrel-treated
      patients, were more likely to have Thrombolysis In Myocardial Infarction
      myocardial perfusion grade of >=2 (79% vs 49%, p = 0.01), lower Thrombolysis In
      Myocardial Infarction frame count (10.2 +/- 5.7 vs 13.6 +/- 7.2, p = 0.03), and a
      numerically greater incidence of early ST-segment resolution >50% (26 of 30 [87%]
      vs 35 of 49 [71%], p = 0.1), suggesting better myocardial reperfusion. In
      conclusion, overall, prasugrel compared with clopidogrel pretreatment resulted in
      greater platelet inhibition at PPCI, but even with prasugrel, only <50% of the
      patients achieved early adequate platelet response.

PMID- 23972350
TI  - Usefulness of high-dose intravenous human immunoglobulins treatment for
      refractory recurrent pericarditis.
AB  - The management of refractory recurrent pericarditis is challenging. Previous
      clinical reports have noted a beneficial effect of high-dose intravenous human
      immunoglobulins (IvIgs) in isolated and systemic inflammatory disease-related
      forms. In this article, we analyzed retrospectively our clinical experience with
      IvIg therapy in a series of clinical cases of pericarditis refractory to
      conventional treatment. We retrospectively analyzed 9 patients (1994 to 2010)
      with refractory recurrent pericarditis, who received high-dose IvIg as a part of
      their medical treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids,
      or colchicine treatment was not discontinued during IvIg treatment. No patients
      had a history of autoimmune or connective tissue diseases. During an average
      period of 11 months from the first recurrence, patients had experienced a mean of
      5 relapses before the first IvIg treatment. In 4 cases, patients showed complete
      clinical remission with no further relapse after the first IvIg cycle. Two
      patients experienced a single minor relapse, responsive to short-term
      nonsteroidal anti-inflammatory drugs. In 2 patients, we performed a second cycle
      of IvIg after a recurrence of pericarditis, with subsequent complete remission.
      One patient did not respond to 3 cycles of IvIg and subsequently underwent
      pericardial window and long-term immunosuppressive treatment. No major adverse
      effect was observed in consequence of IvIg administration in all the cases. In
      conclusion, although IvIg mode of action is still poorly understood in this
      setting, this treatment can be considered as an option in patients with recurrent
      pericarditis refractory to conventional medical treatment and, in our small
      series, has proved to be effective in 8 of 9 cases.

PMID- 23972351
TI  - Flow in the left anterior descending coronary artery in patients with migraine
      headache.
AB  - Migraine is a common neurovascular disorder characterized by attacks of severe
      headache, autonomic and neurologic symptoms. Migraine can affect many systems in
      the body, yet its effects on cardiovascular system are unclear. We hypothesized
      that migraine and coronary microvascular angina may be manifestations of a common
      systemic microvascular dysfunction and clinically associated. Forty patients with
      migraine and 35 healthy volunteers were included into the study. Using
      transthoracic Doppler echocardiography, coronary flow was visualized in the
      middle or distal part of the left anterior descending artery. Coronary diastolic
      peak flow velocities were measured with pulse wave Doppler at baseline and after
      dipyridamole infusion (0.56 mg/kg/4 min). Coronary flow reserve of <2 was
      considered normal. In addition, thorough 2-dimensional and Doppler
      echocardiographic examinations were also performed. Fifty-two women and 23 men
      were included. Coronary flow reserve was significantly lesser in the migraine
      group than in the control group (1.99 +/- 0.3 vs 2.90 +/- 0.5, p <0.05). In
      addition, mitral annular velocities were lower and the ratio of early mitral
      inflow velocity to early mitral annular velocity (E/E' lateral and E/E' septal)
      was higher in migraineurs than in the control group (p <0.05 for all), indicating
      diastolic function abnormalities in the migraine group. In conclusion, these
      findings suggest that there is an association between coronary microvascular
      dysfunction and migraine independently of the metabolic state of the patients. A
      common pathophysiologic pathway of impaired endothelial vasodilatation, vasomotor
      dysfunction, and increased systemic inflammatory factors may play a role in these
      2 clinical conditions and could be the underlying cause of subclinical systolic
      and diastolic left ventricular dysfunction in migraineurs.

PMID- 23972354
TI  - A survey on core competencies of Master of Public Health students in China.

PMID- 23972353
TI  - Timing and gender determine if acute pain impairs working memory performance.
AB  - The effects of pain on memory are complex, and little is known about the
      vulnerability of working memory (WM) performance when individuals complete a WM
      test while concurrently experiencing pain. Here, we subjected 78 healthy
      nonsmoking participants to either acute pain or a control condition while we
      administered a WM test. In this context, we also tested WM 20 minutes after pain
      in order to determine if timing of pain affected WM performance, and assessed
      objective and subjective measures of pain. We hypothesized that pain would impair
      WM performance during pain. Further, women's WM performance would be impaired
      more than men. Importantly, there was an interaction between gender and
      condition, with women exposed to pain experiencing impairments during but not
      after the cold pressor task. Our data imply that timing and gender are critically
      important in whether acute pain is costly to WM performance. Our findings have
      interesting clinical, professional, and educational implications, and
      understanding the influence of pain could help to improve the interpretation of
      WM tests in these diverse settings. PERSPECTIVE: Results of this study support
      the growing body of work that attests to the detrimental effect of pain on WM
      performance. Further, this study provides new evidence that concurrently
      experiencing cold pressor pain impairs WM in regularly menstruating women and
      women taking a contraceptive.

PMID- 23972355
TI  - Sex-age differences in association with particulate matter and emergency
      admissions for cardiovascular diseases: a hospital-based study in Taiwan.
AB  - OBJECTIVE: To explore the association between short-term exposure to particulate
      matter (PM) and cardiovascular diseases (CVDs) emergency room visits. STUDY
      DESIGN: Case-control study. METHODS: 2785 Emergency visits with presented
      cardiovascular diseases and 24,572 controls from ten hospitals in 2005 were
      obtained from a Taiwan's National Health Database. Daily PM10 data and
      meteorological information collected from an air monitoring station near the ten
      hospitals were used to calculate the exposure levels. Using multiple logistic
      regression analysis, adjusted odds ratios (AOR) were estimated for the
      associations of PM and temperature with ischaemic heart disease (IHD) and
      hypertension heart disease (HHD). RESULTS: A positive association (AOR = 1.05
      1.75) between IHD emergency admission among women older than 65 and exposure to
      daily levels of PM10 pollution standard index (PSI) >=50 compared with
      respondents exposed to PM10 PSI <50. CONCLUSIONS: To prevent exacerbation of IHD,
      people, especially elderly women, should be urged to reduce exposure to unhealthy
      PSI levels.

PMID- 23972356
TI  - Distribution and utilization of curative primary healthcare services in Lahej,
      Yemen.
AB  - OBJECTIVE: No evidence-based data exist on the availability, accessibility and
      utilization of healthcare services in Lahej Governorate, Yemen. The aim of this
      study was to assess the distribution and utilization of curative services in
      primary healthcare units and centres in Lahej. STUDY DESIGN: Cross-sectional
      study (clustering sample). METHOD: This study was conducted in three of the 15
      districts in Lahej between December 2009 and August 2010. Household members were
      interviewed using a questionnaire to determine sociodemographic characteristics
      and types of healthcare services available in the area. RESULTS: The distribution
      of health centres, health units and hospitals did not match the size of the
      populations or areas of the districts included in this study. Geographical
      accessibility was the main obstacle to utilization. Factors associated with the
      utilization of curative services were significantly related to the time required
      to reach the nearest facility, seeking curative services during illness and
      awareness of the availability of health facilities (P < 0.01). CONCLUSION: There
      is an urgent need to look critically and scientifically at the distribution of
      healthcare services in the region in order to ensure accessibility and quality of
      services.

PMID- 23972357
TI  - The role of household transmission in an outbreak of viral gastroenteritis in a
      primary school in Liverpool, England.

PMID- 23972358
TI  - Magnolol inhibits colonic motility through down-regulation of voltage-sensitive L
      type Ca2+ channels of colonic smooth muscle cells in rats.
AB  - This study aimed to investigate the effect of magnolol (5,5'-diallyl-2,2'
      biphenyldiol) on contraction in distal colonic segments of rats and the
      underlying mechanisms. Colonic segments were mounted in organ baths for isometric
      force measurement. Whole-cell voltage-sensitive L-type Ca(2+) currents were
      recorded on isolated single colonic smooth muscle cells using patch-clamp
      technique. The spontaneous contractions and acetylcholine (ACh)- and Bay K 8644
      induced contractions were inhibited by magnolol (3-100 MUM). In the presence of
      Bay K8644 (100 nM), magnolol (10-100 MUM) inhibited the contraction induced by 10
      MUM ACh. By contrast, tetrodotoxin (100 nM) and Nomega-nitro-L-arginine methyl
      ester (L-NAME 100 MUM) did not change the inhibitory effect of magnolol (10 MUM).
      In addition, magnolol (3-100 MUM) inhibited the L-type Ca(2+) currents. The
      present results suggest that magnolol inhibits colonic smooth muscle contraction
      through downregulating L-type Ca(2+) channel activity.

PMID- 23972359
TI  - The development of angioedema in a patient with type 2 diabetes due to a novel
      dipeptidyl peptidase-IV inhibitor, anagliptin.

PMID- 23972360
TI  - Trial sequential analysis: the role of the number needed-to-treat in evaluating
      the clinical relevance of relative risk reduction values in the intra-aortic
      balloon pump support.

PMID- 23972361
TI  - Novel abciximab-Kruppel-like factor 4-plasmid dual-delivery titanium dioxide
      coated coronary stent.

PMID- 23972362
TI  - Gene expression profiling in pediatric heart transplant rejection.

PMID- 23972363
TI  - Transcatheter aortic valve implantation (TAVI): valve design and evolution.
AB  - The efficacy of transcatheter aortic valve implantation (TAVI) in high surgical
      risk and inoperable patients with severe aortic stenosis (AS) is rapidly gaining
      credibility with an ever-expanding body of supporting evidence. The potential of
      TAVI to be a treatment option for a significant cohort of patients with aortic
      stenosis has fuelled a drive for the optimum device and resulted in exponential
      advances in the technology with a focus on adverse event minimization and
      procedural simplification. Consequently, a plethora of new transcatheter valve
      choices are now available for clinical study or in the pipeline. The evaluation
      of past, current and emerging devices allows for an appreciation of the design
      considerations involved in this process and an insight to the future direction of
      the technology. 

PMID- 23972364
TI  - Airway obstruction in patients with cardiac diseases.

PMID- 23972365
TI  - Three-dimensional optical coherence tomography evaluation of a left main
      bifurcation lesion treated with ABSORB(r) bioresorbable vascular scaffold
      including fenestration and dilatation of the side branch.

PMID- 23972366
TI  - Effectiveness of drug-eluting balloons: quantifying the information size from
      clinical trials.

PMID- 23972367
TI  - Greek underpinnings to his methodology in unraveling De Motu Cordis and what
      Harvey has to teach us still today.
AB  - William Harvey's writings betray amazing insights born out of countless hours of
      thoughtful experimentation. Throughout his life, Harvey worked as a tireless and
      thoughtful researcher and a transmitter and intermediary between the ancient
      Greek natural philosophers and physicians and the "moderns," for whom he founded
      two forward-looking, interlinked sciences: modern physiology and nascent
      cardiology. Harvey's methodology and demonstrations were of such fundamental and
      standardizing nature as to secure the sure progress of these two sciences. Thus,
      he rendered to them such a service as Descartes's cogito ergo sum furnished to
      Philosophy in giving it a rational standard of certainty, for want of which the
      more speculative minds of that era were inundated with extraordinary conjectures.
      If Harvey disproved Galen, he absorbed and continued in his physiologic research
      many a principle from Aristotle, whose supreme disciple he remains. The guidance
      and authority of Aristotle were strong with him to the end. Harvey's account of
      the motions of the heart and blood in the circulation demonstrated that complex
      physiological systems can be represented in straightforward mechanical terms, a
      concept which has remained fundamental to the present day. The philosophical
      implication of William Harvey's discovery of the circulation of the blood was the
      resolute application of the experimental method to cardiology. In my judgment, he
      established today's forward-looking discipline of translational cardiovascular
      research. In due course, he should be widely acknowledged to have done so. 

PMID- 23972368
TI  - Prognostic influence of prior ischemic heart disease in in-hospital mortality of
      acute coronary syndromes.

PMID- 23972369
TI  - Sequential changes in renal function and the risk of stroke and death in patients
      with atrial fibrillation.
AB  - BACKGROUND: Renal dysfunction has been proposed for the risk factor for stroke
      and bleeding in atrial fibrillation (AF). The impact of changes in renal
      dysfunction over time and the relationship to stroke and bleeding risk in these
      patients remain unknown. We investigated sequential change in renal function
      (estimated glomerular filtration rate, eGFR) and the risk for clinical events
      (ischaemic stroke, death and major bleeding) over time in a cohort of 617 AF
      patients followed up for 2 years. METHODS: eGFR was estimated at baseline, 6
      months and 12 months using three formulas (Modification of Diet in Renal Disease
      equation, MDRD, Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI, and
      Cockcroft-Gault equation). Changes in eGFR and the risk for clinical events were
      analysed by Cox models, receiver operating curves (ROC), and Kaplan-Meier
      survival curves. RESULTS: When patients with eGFR<=60 ml/min/1.73 m(2) were
      compared to patients with eGFR>60 ml/min/1.73 m(2), there was an increase over
      time in stroke or death, or death, with impaired renal function (all p<0.05). An
      absolute decrease in eGFR>=15 ml/min/1.73 m(2) on Cockcroft-Gault and CKD-EPI and
      >=25 ml/min/1.73 m(2) on MDRD were associated with an increased risk for stroke
      or death, death, and ischaemic stroke at 6 months (all p<0.05), but not major
      bleeding. A relative reduction (decline of >=25%) in eGFR was also an independent
      risk. ROC analysis showed that a relative reduction in eGFR >=25% at 6 months and
      12 months modestly predicted the occurrence of stroke or death in patients with
      AF (c-indexes: 0.57 to 0.61, p<0.05). CONCLUSION: In patients with AF, an
      absolute decrease in eGFR >=15 ml/min/1.73 m(2) on Cockcroft-Gault and CKD-EPI,
      and >=25 ml/min/1.73 m(2) on MDRD, or a relative reduction (>=25%) in eGFR,
      independently predicted the risk for the endpoints 'stroke or death', 'death' or
      (at 6 months) ischaemic stroke. Deteriorating renal function increases the risk
      of death in AF patients.

PMID- 23972370
TI  - BMP9 mutations cause a vascular-anomaly syndrome with phenotypic overlap with
      hereditary hemorrhagic telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular
      disorder, is caused by mutations in genes involved in the transforming growth
      factor beta (TGF-beta) signaling pathway (ENG, ACVRL1, and SMAD4). Yet,
      approximately 15% of individuals with clinical features of HHT do not have
      mutations in these genes, suggesting that there are undiscovered mutations in
      other genes for HHT and possibly vascular disorders with overlapping phenotypes.
      The genetic etiology for 191 unrelated individuals clinically suspected to have
      HHT was investigated with the use of exome and Sanger sequencing; these
      individuals had no mutations in ENG, ACVRL1, and SMAD4. Mutations in BMP9 (also
      known as GDF2) were identified in three unrelated probands. These three
      individuals had epistaxis and dermal lesions that were described as
      telangiectases but whose location and appearance resembled lesions described in
      some individuals with RASA1-related disorders (capillary malformation
      arteriovenous malformation syndrome). Analyses of the variant proteins suggested
      that mutations negatively affect protein processing and/or function, and a bmp9
      deficient zebrafish model demonstrated that BMP9 is involved in angiogenesis.
      These data confirm a genetic cause of a vascular-anomaly syndrome that has
      phenotypic overlap with HHT. 

PMID- 23972372
TI  - Mutations in DDX59 implicate RNA helicase in the pathogenesis of orofaciodigital
      syndrome.
AB  - Orofaciodigital syndrome (OFD) is a recognized clinical entity with core defining
      features in the mouth, face, and digits, in addition to various other features
      that have been proposed to define distinct subtypes. The three genes linked to
      OFD-OFD1, TMEM216, and TCTN3-play a role in ciliary biology, a finding consistent
      with the clinical overlap between OFD and other ciliopathies. Most autosomal
      recessive cases of OFD, however, remain undefined genetically. In two multiplex
      consanguineous Arab families affected by OFD, we identified a tight linkage
      interval in chromosomal region 1q32.1. Exome sequencing revealed a different
      homozygous variant in DDX59 in each of the two families, and at least one of the
      two variants was accompanied by marked reduction in the level of DDX59. DDX59
      encodes a relatively uncharacterized member of the DEAD-box-containing RNA
      helicase family of proteins, which are known to play a critical role in all
      aspects of RNA metabolism. We show that Ddx59 is highly enriched in its
      expression in the developing murine palate and limb buds. At the cellular level,
      we show that DDX59 is localized dynamically to the nucleus and the cytoplasm.
      Consistent with the absence of DDX59 representation in ciliome databases and our
      demonstration of its lack of ciliary localization, ciliogenesis appears to be
      intact in mutant fibroblasts but ciliary signaling appears to be impaired. Our
      data strongly implicate this RNA helicase family member in the pathogenesis of
      OFD, although the causal mechanism remains unclear. 

PMID- 23972373
TI  - The relative effect of health literacy and patient activation on provider choice
      in the Netherlands.
AB  - Active provider choice by patients has become an important policy theme in
      western, countries over the last decades. However, not many patients and
      consumers exercise their right to, choose. Both health literacy and patient
      activation are likely to have an impact on the choice process. In, this article
      the relative effect of health literacy and patient activation on provider choice
      in the, Netherlands is studied. A questionnaire was sent to a representative
      sample of 2000 Dutch citizens. The questionnaire, included a measure of
      functional health literacy, the Dutch version of the Patient Activation Measure,
      and questions assessing active provider choice, reasons not to engage in it and
      other ways of provider, selection. The majority of respondents (59.6%) would not
      search for information on the basis of which they, could select the best provider
      or hospital. Most people rely on their general practitioner's advice. Both, low
      literacy and lower patient activation levels were negatively associated with
      active provider choice. In a regression analysis gender, education and patient
      activation proved the most important, predictors. The policy focus on active
      provider choice might result in inequity, with men, less educated, and less
      activated people being at a disadvantage. 

PMID- 23972374
TI  - Effect of the transverse ligament rupture on the biomechanics of the cervical
      spine under a compressive loading.
AB  - BACKGROUND: In order to diagnosis a transverse ligament rupture in the cervical
      spine, clinicians normally measure the atlas-dens interval by using CT scan
      images. However, the impact of this tear on the head and neck complex
      biomechanics is not widely studied. The transverse ligament plays a very
      important role in stabilizing the joint and its alteration may have a substantial
      effect on the whole head and neck complex. METHODS: A finite element model
      consisting of bony structures along with cartilage, intervertebral discs and all
      ligaments was developed based on CT and MRI images. The effect of head weights
      (compressive load) of 30 N to 57 N was investigated in the cases of intact and
      ruptured transverse ligament joints. The model was validated based on
      experimental studies investigating the response of the cervical spine under the
      extension-flexion moment. FINDINGS: The predictions indicate a significant
      alteration of the kinematics and load distribution at the facet joints of the
      cervical spine with a transverse ligament tear. The vertebrae flexion, the
      contact force at the facets joints and the atlas-dens interval increase with the
      rupture of the transverse ligament and are dependent to the head weight.
      INTERPRETATION: A transverse ligament tear increases the flexion angle of the
      head and the vertebrae as well as the atlas-dens interval. The atlas-dens
      interval reaches a critical value when the compressive loading exceeds 40 N.
      Supporting the head after an injury should be considered to avoid compression of
      the spinal cord and permanent neurologic damage.

PMID- 23972371
TI  - Genome-wide association analysis of blood-pressure traits in African-ancestry
      individuals reveals common associated genes in African and non-African
      populations.
AB  - High blood pressure (BP) is more prevalent and contributes to more severe
      manifestations of cardiovascular disease (CVD) in African Americans than in any
      other United States ethnic group. Several small African-ancestry (AA) BP genome
      wide association studies (GWASs) have been published, but their findings have
      failed to replicate to date. We report on a large AA BP GWAS meta-analysis that
      includes 29,378 individuals from 19 discovery cohorts and subsequent replication
      in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395),
      and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1,
      and SOX6) reached genome-wide significance (p < 1.0 * 10(-8)) for either systolic
      or diastolic BP in a transethnic meta-analysis after correction for multiple
      testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous
      associations with BP. We also identified one independent signal in a known BP
      locus (SOX6) and provide evidence for fine mapping in four additional validated
      BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly,
      show significant effects in AA samples. Consequently, these findings suggest that
      BP loci might have universal effects across studied populations, demonstrating
      that multiethnic samples are an essential component in identifying, fine mapping,
      and understanding their trait variability. 

PMID- 23972375
TI  - Comparison of outcomes of perinatal care in Slovakia and the UK.
AB  - OBJECTIVE: To investigate whether there are differences in maternal and perinatal
      outcomes between Slovakia and the UK, and whether any observed variations can be
      attributed to differences in perinatal care. METHODS: Data on outcomes of
      perinatal care in Slovakia and the UK between 2006 and 2010 were compared.
      Perinatal mortality figures included stillbirths weighing 1000g or more and early
      neonatal deaths. RESULTS: In Slovakia, the perinatal mortality rate was
      significantly higher than that in the UK (RR 1.12; 95% CI, 1.06-1.18). Cesarean
      delivery was significantly more frequent in Slovakia (RR 1.05; 95% CI, 1.05
      1.06); instrumental vaginal delivery was less frequent (ventouse delivery, RR
      0.20; 95% CI, 0.19-0.21; forceps delivery, RR 0.09; 95% CI, 0.09-0.10).
      Episiotomy and peripartum hysterectomy were performed more often in Slovakia
      (episiotomy, RR 4.10; 95% CI, 4.07-4.12; peripartum hysterectomy, RR 2.02; 95% CI
      1.65-2.47). The incidence of eclampsia was significantly higher in Slovakia (RR
      1.60; 95% CI, 1.26-2.04). There were no significant differences in the rates of
      maternal death. CONCLUSION: Perinatal care outcomes and intervention rates differ
      between Slovakia and UK. This may be explained by differences in outcome
      definitions, perinatal care, and official encouragement of medical complaints.

PMID- 23972376
TI  - Enlarged laminectomy and lateral mass screw fixation for multilevel cervical
      degenerative myelopathy associated with kyphosis.
AB  - BACKGROUND CONTEXT: Either an anterior approach or a posterior approach, which
      aims to decompress the spinal cord and restore the sagittal alignment, has been
      adopted to treat multilevel cervical degenerative myelopathy (CDM) associated
      with kyphosis. However, there is controversy on the optimal surgical strategy for
      the treatment of multilevel CDM with kyphotic deformity because of the
      complications of each surgical approach. PURPOSE: The purpose of this study was
      to investigate the surgical efficacy of enlarged laminectomy (removing the inside
      edge of facet joints and decompressing the nerve foramina) and lateral mass screw
      fixation for the treatment of multilevel CDM associated with kyphosis. STUDY
      DESIGN: A retrospective radiographic and clinical study to access the efficacy of
      enlarged laminectomy with lateral mass screw fixation in the treatment of
      multilevel CDM related to kyphosis. PATIENT SAMPLE: A total of 43 patients (28
      men and 15 women; average age, 59.6 years) with multilevel CDM correlated to
      kyphosis were obtained in the study. OUTCOME MEASURES: All radiological data were
      recorded on computer-based measurement from preoperative or postoperative X-ray,
      magnetic resonance imaging (MRI), and computed tomography. All neurological
      parameters were accessed in each patient. METHODS: Analysis consisted of:
      Japanese Orthopedic Association (JOA) score, recovery rate, curvature index (CI),
      the expansion degree and drift-back distance of the spinal cord, axial symptom
      severity, and C5 root palsy. The recovery rate based on the JOA score was
      calculated for each patient. Cervical CI as well as the expansion degree and
      drift-back distance of the spinal cord was measured using MRI. Axial symptom
      severity was quantified by a visual analog scale (VAS). Statistical analysis was
      performed using paired t test with significance set at p<.05. RESULTS: Enlarged
      laminectomy was performed over a mean of 3.97 levels (range, 3-5 levels). Follow
      up information was obtained at a mean of 2.8 years (range, 1.5-5 years) after
      surgery. Analysis of the final follow-up data showed significant differences
      before and after surgery in the JOA score (t=24.17, p<.001), CI improvement
      (t=21.89, p<.001), the anteroposterior diameter at the level of maximum
      compression of the spinal cord (t=9.54, p<.001), and VAS score (t=13.30, p<.001).
      The mean spinal cord posterior shift was 4.72+/-1.10 mm (range, 0-6.71 mm). X
      rays confirmed that bone grafts were completely fused at a mean of 3 months after
      surgery. During the follow-up period, only two patients (4.7%) did not obtain
      complete recovery, four patients (9.3%) experienced axial symptoms; there were no
      C5 root palsy and instrument failures noted in this series. CONCLUSION: Enlarged
      laminectomy with fixation for the management of multilevel CDM is demonstrated to
      be an effective strategy for improving neurological function, restoring the
      normal cervical lordosis, and decreasing the incidence of axial symptoms and C5
      root palsy, but there is a need for randomized controlled studies with long-term
      follow-up to confirm and clarify these results.

PMID- 23972377
TI  - Quantitative assessment of acoustic intensity in the focused ultrasound field
      using hydrophone and infrared imaging.
AB  - With the popularity of ultrasound therapy in clinics, characterization of the
      acoustic field is important not only to the tolerability and efficiency of
      ablation, but also for treatment planning. A quantitative method was introduced
      to assess the intensity distribution of a focused ultrasound beam using a
      hydrophone and an infrared camera with no prior knowledge of the acoustic and
      thermal parameters of the absorber or the configuration of the array elements.
      This method was evaluated in both theoretical simulations and experimental
      measurements. A three-layer model was developed to calculate the acoustic field
      in the absorber, the absorbed acoustic energy during the sonication and the
      consequent temperature elevation. Experiments were carried out to measure the
      acoustic pressure with the hydrophone and the temperature elevation with the
      infrared camera. The percentage differences between the derived results and the
      simulation are <4.1% for on-axis intensity and <21.1% for -6-dB beam width at
      heating times up to 360 ms in the focal region of three phased-array ultrasound
      transducers using two different absorbers. The proposed method is an easy, quick
      and reliable approach to calibrating focused ultrasound transducers with
      satisfactory accuracy. 

PMID- 23972378
TI  - Establishment and characterization of a canine xenograft model of inflammatory
      mammary carcinoma.
AB  - Canine inflammatory mammary cancer (IMC) and human inflammatory breast cancer
      (IBC) are the most aggressive form of mammary/breast cancer. Both species
      naturally develop it, sharing epidemiological, clinical and histological
      characteristics. Thus, IMC has been suggested as a model to study the human
      disease. We have developed the first IMC xenograft model in SCID mice. Xenografts
      reproduced the histological features from the primary tumor, were highly
      aggressive and showed dermal tumor emboli, distinctive hallmarks of IMC/IBC. This
      model was hormone receptors positive and HER2 negative. Our findings showed that
      estrogens and androgens are locally produced in tissues. Factors related to tumor
      vascularization showed positive expression and xenografts with the highest
      expression of all analyzed vascular factors had the highest rate of tumor
      proliferation. The role of steroid hormones and the angio/lymphangiogenic
      properties found in this model, provide additional knowledge for future
      interventions in the diagnosis, treatment and prevention of the disease. 

PMID- 23972379
TI  - Introduction to the special issue historical medical genetics: skeletal
      disorders.

PMID- 23972380
TI  - [Abstracts of the 30th Congress of the French Society of Endocrinology, 2013,
      Paris, France].

PMID- 23972382
TI  - Nationwide survey of rotavirus-associated encephalopathy and sudden unexpected
      death in Japan.
AB  - BACKGROUND: Rotavirus can cause severe complications such as
      encephalopathy/encephalitis and sudden unexpected death. The incidence of
      rotavirus-associated encephalopathy/encephalitis or sudden unexpected death
      remains unknown. To clarify the clinical features of rotavirus-associated
      encephalitis/encephalopathy and sudden unexpected death, we conducted a
      nationwide survey in Japan. METHOD: A two-part questionnaire was designed to
      determine the number of the cases and the clinical features of severe cases of
      rotavirus infection, including encephalitis/encephalopathy and sudden unexpected
      death, between 2009 and 2011. RESULT: Of the 1365 questionnaires sent to
      hospitals, 963 (70.5%) were returned and eligible for analysis. We determined 58
      cases of rotavirus-associated encephalitis/encephalopathy and 7 cases of sudden
      unexpected death. These patients were diagnosed with rotavirus infection by
      immunochromatography. Although 36/58 (62.1%) encephalitis/encephalopathy patients
      had no sequelae, 15/58 (25.9%) patients had neurological sequelae, and 7/58
      (12.1%) patients had fatal outcomes. Pleocytosis was observed in 9/40 (22.5%)
      patients and cerebrospinal fluid protein levels were elevated in only 4/40 (10%)
      patients. Elevated lactate dehydrogenase (LDH) (>500 IU/L) or acidemia (pH<7.15)
      were related to a poor prognosis. CONCLUSION: We estimate that annual cases of
      rotavirus-associated encephalitis/encephalopathy and sudden unexpected death were
      44.0 and 4.9 cases in Japan, respectively. Elevated LDH (>500 IU/L) or acidemia
      (pH<7.15) were related to a poor prognosis of the encephalitis/encephalopathy.

PMID- 23972381
TI  - Sex differences in asthma symptom profiles and control in the American Lung
      Association Asthma Clinical Research Centers.
AB  - OBJECTIVE: Important differences between men and women with asthma have been
      demonstrated, with women describing more symptoms and worse asthma-related
      quality of life (QOL) despite having similar or better pulmonary function. While
      current guidelines focus heavily on assessing asthma control, they lack
      information about whether sex-specific approaches to asthma assessment should be
      considered. We sought to determine if sex differences in asthma control or
      symptom profiles exist in the well-characterized population of participants in
      the American Lung Association Asthma Clinical Research Centers (ALA-ACRC) trials.
      METHODS: We reviewed baseline data from four trials published by the ALA-ACRC to
      evaluate individual item responses to three standardized asthma questionnaires:
      the Juniper Asthma Control Questionnaire (ACQ), the multi-attribute Asthma
      Symptom Utility Index (ASUI), and Juniper Mini Asthma Quality of Life
      Questionnaire (mini-AQLQ). RESULTS: In the poorly-controlled population, women
      reported similar overall asthma control (mean ACQ 1.9 vs. 1.8; p = 0.54), but
      were more likely to report specific symptoms such as nocturnal awakenings,
      activity limitations, and shortness of breath on individual item responses. Women
      reported worse asthma-related QOL on the mini-AQLQ (mean 4.5 vs. 4.9; p < 0.001)
      and more asthma-related symptoms with a lower mean score on the ASUI (0.73 vs.
      0.77; p <= 0.0001) and were more likely to report feeling bothered by particular
      symptoms such as coughing, or environmental triggers. CONCLUSIONS: In
      participants with poorly-controlled asthma, women had outwardly similar asthma
      control, but had unique symptom profiles on detailed item analyses which were
      evident on evaluation of three standardized asthma questionnaires.

PMID- 23972383
TI  - New insights in mucopolysaccharidosis type VI: neurological perspective.
AB  - OBJECTIVE: Mucopolysaccharidosis type VI is a rare autosomal recessive storage
      disorder, caused by deficiency of arylsulfatase B. Data on neurological
      involvement in mucopolysaccharidosis type VI patients under enzyme-replacement
      therapy are limited. This study explores the neurological and magnetic resonance
      imaging findings in a sample of mucopolysaccharidosis type VI patients receiving
      enzyme-replacement therapy. METHODS: We performed a cross-sectional study
      including six patients with biochemical confirmation of mucopolysaccharidosis
      type VI and at least 105 consecutive weeks (two years) receiving intravenous
      enzyme-replacement therapy. The protocol included a comprehensive clinical
      examination, brain and spinal cord magnetic resonance imaging for all subjects.
      RESULTS: Overall, cognition was spared, while we found presence of hearing
      impairment, increasing in deep tendon reflexes and deep sensation reduction in
      three patients. In addition to the classical abnormalities related to other types
      of mucopolysaccharidosis, imaging studies demonstrated morphological changes in
      anatomy of middle cranial fossa and sella shape. Even in asymptomatic or mild
      compromised patients, spinal cord compression was found. In four patients we
      noticed atlantoaxial joint subluxation and three had cervical spinal stenosis.
      Degenerative processes involving vertebral column, including discal protrusion
      and axis abnormalities, were present in all patients. CONCLUSIONS: Neuroaxis
      involvement was a universal finding and neurological examination might not
      predict the severity of the disease in course. Image studies should not be
      performed according exclusively clinical parameters for these patients, once we
      have demonstrated that neurological involvement may be silent in these patients.

PMID- 23972384
TI  - Iris-fixated phakic intraocular lens implantation after retinal detachment
      surgery: long-term clinical results.
AB  - PURPOSE: To assess the efficacy and safety of iris-fixated phakic intraocular
      lens (pIOL) implantation to correct myopia in eyes with previous retinal
      detachment (RD) surgery. SETTING: Department of Ophthalmology, Soonchunhyang
      University College of Medicine, Seoul, South Korea. DESIGN: Retrospective case
      series. METHODS: Patients having pIOL implantation in both eyes were enrolled.
      Eyes that had scleral buckling or encircling (RD group) and healthy fellow eyes
      (non-RD group) were evaluated over a 6-year follow-up. The corrected distance
      visual acuity (CDVA), endothelial cell density (ECD), intraoperative
      complications, and long-term complications were safety outcomes. Uncorrected
      distance visual acuity (UDVA), predictability, and stability of refraction were
      efficacy outcomes. RESULTS: The study comprised 34 eyes (17 patients). The mean
      postoperative CDVA and ECD were not significantly different between groups, and
      no patient lost CDVA. The rate of transient intraocular pressure spike was
      significantly higher in the RD group (P=.043). After 3 years and 6 years, the
      mean postoperative UDVA was 0.06 logMAR +/- 0.09 (SD) and 0.08 +/- 0.10 logMAR,
      respectively, in the RD group and 0.04 +/- 0.08 logMAR and 0.04 +/- 0.09 logMAR,
      respectively, in the non-RD group (P=.518 and P=.478, respectively). The rate of
      eyes within +/-0.50 diopter of the desired refraction and the postoperative
      refraction was not significantly different between groups. No eye had
      vitreoretinal changes requiring secondary surgical intervention. CONCLUSION: Iris
      fixated pIOL implantation corrected the myopic refractive error in patients who
      had scleral buckling or encircling surgery for RD with a high degree of efficacy,
      safety, and long-term stability. FINANCIAL DISCLOSURE: No author has a financial
      or proprietary interest in any material or method mentioned.

PMID- 23972385
TI  - Collagen copolymer posterior chamber phakic intraocular lens for hyperopia
      correction: three-year follow-up.
AB  - PURPOSE: To assess the efficacy, predictability, safety, and stability of the
      Visian V3 Implantable Collamer Lens posterior chamber phakic intraocular lens (PC
      pIOL) for moderate to high hyperopia. SETTING: Private clinic, Oviedo, Spain.
      DESIGN: Prospective nonrandomized clinical study. METHODS: The uncorrected (UDVA)
      and corrected (CDVA) distance visual acuities, manifest refraction, endothelial
      cell density, intraocular pressure (IOP), central vault, and adverse events were
      evaluated for 3 years postoperatively. RESULTS: The study comprised 73 eyes of 44
      patients. The mean spherical equivalent decreased from +4.84 diopters (D) +/- 1.6
      (SD) (range +1.00 to +7.75 D) preoperatively to -0.13 +/- 0.39 D 3 years
      postoperatively; 61 eyes (83.6%) were within +/-0.50 D of the target refraction
      and all eyes were within +/-1.00 D. The mean postoperative Snellen decimal UDVA
      and CDVA was 0.86 +/- 0.17 and 0.91 +/- 0.16, respectively. Most eyes (91.8%) had
      no change from the preoperative CDVA or gained 1 or more lines. One eye (1.4%)
      lost 2 lines, and no eye lost more than 2 lines. Three years postoperatively, the
      efficacy index was 1.02 and the safety index was 1.08. The IOP remained stable
      over time, with no significant increase postoperatively. The mean endothelial
      cell loss was 4.7%, remaining unchanged over time. No postoperative complications
      or adverse events, including pupillary block or secondary cataract, occurred.
      CONCLUSIONS: Implantation of the PC pIOL was safe and effective in correcting
      hyperopic refractive errors, with stable visual and refractive outcomes.
      FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any
      material or method mentioned.

PMID- 23972386
TI  - Subacute exogenous Rhizoctonia solani endophthalmitis following cataract
      extraction with intraocular lens implantation.
AB  - Seven weeks after uneventful cataract extraction with intraocular lens (IOL)
      implantation, a 64-year-old man presented to his cataract surgeon with decreased
      vision and photophobia. The subacute presentation with anterior uveitis prompted
      initial therapy with topical and periocular glucocorticoids. One month later, the
      patient presented to the vitreoretinal service with counting fingers visual
      acuity, prominent anterior chamber reaction, a 2.5 mm hypopyon, and inflammatory
      deposits over the IOL. Cultures grew Rhizoctonia solani. The inflammation was
      successfully treated with pars plana vitrectomy, IOL explantation, and
      intravitreal voriconazole. Rhizoctonia should be included in the differential
      diagnosis of subacute exogenous endophthalmitis, especially in the context of
      fibrillar white IOL plaques. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 23972388
TI  - The posterior two-portal approach for reconstruction of scapula fractures:
      results of 39 patients.
AB  - The purpose of this study was to describe the so-called posterior two-portal
      approach to the scapula in detail and to investigate the clinical outcome of
      patients with displaced glenoid and scapular neck fractures who were surgically
      treated using this approach. From February 1992 to August 2008, 39 patients (30
      men and nine women; mean age: 53 years) with scapular fractures underwent
      surgical fixation at our institution. Thirty-three patients had glenoid fractures
      and six had unstable scapular neck fractures. All patients were treated via the
      two-portal approach. The reduction was evaluated radiographically, and the
      clinical results were analysed using the Constant score. The mean follow-up
      period was 78 months (range: 6-168). In 24 of the 33 glenoid fractures, the
      reduction was anatomical. The mean Constant score was 82.3 (range: 35-100)
      points. In one case, an early postoperative wound infection was cured by local
      revision, and one patient developed posttraumatic osteoarthritis of the
      acromioclavicular joint after 2 years. Only one patient developed specific
      glenohumeral degeneration after non-anatomical reduction. The posterior two
      portal approach allows for a good visualisation of the posterior scapular neck
      and the glenoid area, facilitating the reduction and safe internal fixation of
      dislocated scapular neck and glenoid fractures. 

PMID- 23972387
TI  - Finding the lost treasures in exome sequencing data.
AB  - Exome sequencing is one of the most cost-efficient sequencing approaches for
      conducting genome research on coding regions. However, significant portions of
      the reads obtained in exome sequencing come from outside of the designed target
      regions. These additional reads are generally ignored, potentially wasting an
      important source of genomic data. There are three major types of unintentionally
      sequenced read that can be found in exome sequencing data: reads in introns and
      intergenic regions, reads in the mitochondrial genome, and reads originating in
      viral genomes. All of these can be used for reliable data mining, extending the
      utility of exome sequencing. Large-scale exome sequencing data repositories, such
      as The Cancer Genome Atlas (TCGA), the 1000 Genomes Project, National Heart,
      Lung, and Blood Institute (NHLBI) Exome Sequencing Project, and The Sequence
      Reads Archive, provide researchers with excellent secondary data-mining
      opportunities to study genomic data beyond the intended target regions. 

PMID- 23972389
TI  - Interictal estimation of intracranial seizure onset in temporal lobe epilepsy.
AB  - OBJECTIVES: To evaluate the lateralizing and localizing values of interictal
      focal slow activity (IFSA), single pulse electrical stimulation (SPES) and
      (18)FDG PET, in order to estimate their potential to complement ictal
      intracranial recordings and reduce prolonged monitoring in patients with temporal
      lobe epilepsy. METHODS: The study includes 30 consecutive patients with bilateral
      temporal subdural electrodes and focal seizure onset. IFSA, SPES and (18)FDG PET
      when available, were visually assessed and their combined lateralization was
      based on the majority of the individual lateralizing tests. RESULTS: In the 18
      patients who had all three tests, lateralization was congruent with seizure onset
      areas in 15 (83%). When lateralized (15 patients), (18)FDG PET was always
      congruent with intracranial seizure onset. In all 12 patients without (18)FDG
      PET, lateralization combining IFSA and SPES was congruent with seizure onset,
      including two with bilateral independent seizure onset on subdural monitoring. 22
      out of the 23 patients who had surgery enjoyed favorable outcome (Engel I or II).
      CONCLUSION: Intracranial IFSA and SPES can reliably predict the side and site
      (mesial versus lateral temporal) of seizure onset when they lateralize to the
      same side. SIGNIFICANCE: (18)FDG PET can be useful in planning electrode
      implantation. During intracranial recordings, IFSA and SPES have the potential to
      reduce telemetry time, risks and costs.

PMID- 23972390
TI  - Pulmonary arterial wall stiffness and its impact on right ventricular afterload
      in patients with repaired tetralogy of Fallot.
AB  - BACKGROUND: Recent histologic studies involving patients with tetralogy of Fallot
      (TOF) have revealed a reduction in normal elastic fibers in the pulmonary trunk.
      Such histologic changes may significantly alter the mechanical properties of the
      arterial wall and may thereby augment the pulsatile afterload on the right
      ventricle (RV) and propagate RV dilation and dysfunction. METHODS: We studied 29
      patients with repaired TOF (median age, 5.9 years) and 29 age-matched controls.
      Pulmonary arterial hemodynamics were investigated by measuring the pulmonary
      input impedance during cardiac catheterization. RESULTS: Patients with TOF had
      higher characteristic impedance (p = 0.0002), lower total pulmonary vascular
      compliance (p < 0.0001), and enhanced wave reflection (p < 0.0001). Consistent
      with these changes, patients with TOF were subject to higher pulsatile load,
      measured by fundamental frequency impedance (p < 0.0001), which was significantly
      related to both reduced RV output and increased RV end-diastolic volume (p =
      0.006 and 0.003, respectively). Moreover, pulmonary arterial compliance was
      strongly related to RV end-diastolic volume (r = -0.69, p = 0.0001). In
      multivariate analysis, pulmonary arterial compliance was a significant predictor
      of RV dilation independent of pulmonary regurgitation and pulmonary stenosis (p =
      0.03). CONCLUSIONS: In line with known histologic changes, pulmonary arterial
      stiffness is increased and is significantly related to reduced RV ejection and RV
      enlargement in patients with repaired TOF. These results suggest that not only
      pulmonary valvular function (pulmonary regurgitation/pulmonary stenosis) but also
      pulmonary vascular pulsatile properties can be an important therapeutic target to
      improve prognosis in this population.

PMID- 23972391
TI  - A "polypoid" nipple: an unusual case of epidermoid cyst.

PMID- 23972392
TI  - Invited comment: Vascularized composite allotransplantation: an update on medical
      and surgical progress and remaining challenges.

PMID- 23972393
TI  - Serotonin and the neuropeptide PDF initiate and extend opposing behavioral states
      in C. elegans.
AB  - Foraging animals have distinct exploration and exploitation behaviors that are
      organized into discrete behavioral states. Here, we characterize a
      neuromodulatory circuit that generates long-lasting roaming and dwelling states
      in Caenorhabditis elegans. We find that two opposing neuromodulators, serotonin
      and the neuropeptide pigment dispersing factor (PDF), each initiate and extend
      one behavioral state. Serotonin promotes dwelling states through the MOD-1
      serotonin-gated chloride channel. The spontaneous activity of serotonergic
      neurons correlates with dwelling behavior, and optogenetic modulation of the
      critical MOD-1-expressing targets induces prolonged dwelling states. PDF promotes
      roaming states through a Galphas-coupled PDF receptor; optogenetic activation of
      cAMP production in PDF receptor-expressing cells induces prolonged roaming
      states. The neurons that produce and respond to each neuromodulator form a
      distributed circuit orthogonal to the classical wiring diagram, with several
      essential neurons that express each molecule. The slow temporal dynamics of this
      neuromodulatory circuit supplement fast motor circuits to organize long-lasting
      behavioral states. 

PMID- 23972395
TI  - Biodiesel fuel production from waste cooking oil by the inclusion complex of
      heteropoly acid with bridged bis-cyclodextrin.
AB  - The inclusion complex of Cs2.5H0.5PW12O40 with bridged bis-cyclodextrin (CsPW/B)
      is prepared as a highly efficient catalyst for the direct production of biodiesel
      via the transesterification of waste cooking oil. CsPW/B is characterized by X
      ray diffraction, and the biodiesel is analyzed by Gas Chromatography-Mass
      Spectrometer. The conversion rate of waste cooking oil is up to 94.2% under the
      optimum experimental conditions that are methanol/oil molar ratio of 9:1,
      catalyst dosage of 3 wt%, temperature of 65  degrees C and reaction time of 180
      min. The physical properties of biodiesel sample satisfy the requirement of ASTM
      D6751 standards. The novel CsPW/B catalyst used for the transesterification can
      lead to 96.9% fatty acid methyl esters and 86.5% of the biodiesel product can
      serve as the ideal substitute for diesel fuel, indicating its excellent potential
      application in biodiesel production.

PMID- 23972394
TI  - Short hairpin RNA-mediated knockdown of VEGFA in Muller cells reduces
      intravitreal neovascularization in a rat model of retinopathy of prematurity.
AB  - Vascular endothelial growth factor (VEGF) A is implicated in aberrant
      angiogenesis and intravitreous neovascularization (IVNV) in retinopathy of
      prematurity (ROP). However, VEGFA also regulates retinal vascular development and
      functions as a retinal neural survival factor. By using a relevant ROP model, the
      50/10 oxygen-induced retinopathy (OIR) model, we previously found that broad
      inhibition of VEGFA bioactivity using a neutralizing antibody to rat VEGF
      significantly reduced IVNV area compared with control IgG but also significantly
      reduced body weight gain in the pups, suggesting an adverse effect. Therefore, we
      propose that knockdown of up-regulated VEGFA in cells that overexpress it under
      pathological conditions would reduce IVNV without affecting physiological retinal
      vascular development or overall pup growth. Herein, we determined first that the
      VEGFA mRNA signal was located within the inner nuclear layer corresponding to
      CRALBP-labeled Muller cells of pups in the 50/10 OIR model. We then developed a
      lentiviral-delivered miR-30eembedded shRNA against VEGFA that targeted Muller
      cells. Reduction of VEGFA by lentivector VEGFA-shRNAetargeting Muller cells
      efficiently reduced 50/10 OIR up-regulated VEGFA and IVNV in the model, without
      adversely affecting physiological retinal vascular development or pup weight
      gain. Knockdown of VEGFA in rat Muller cells by lentivector VEGFA-shRNA
      significantly reduced VEGFR2 phosphorylation in retinal vascular endothelial
      cells. Our results suggest that targeted knockdown of overexpressed VEGFA in
      Muller cells safely reduces IVNV in a relevant ROP model.

PMID- 23972396
TI  - Effect of dissimilatory Fe(III) reducers on bio-reduction and nickel-cobalt
      recovery from Sukinda chromite-overburden.
AB  - The effect of an adapted dissimilatory iron reducing bacterial consortium (DIRB)
      towards bio-reduction of Sukinda chromite overburden (COB) with enhanced recovery
      of nickel and cobalt is being reported for the first time. The remarkable ability
      of DIRB to utilize Fe(III) as terminal electron acceptor reducing it to Fe(II)
      proved beneficial for treatment of COB as compared to previous reports for nickel
      leaching. XRD studies showed goethite as the major iron-bearing phase in COB.
      Under facultative anaerobic conditions, goethite was reduced to hematite and
      magnetite with the exposure of nickel oxide. FESEM studies showed DIRB to be
      associated with COB through biofilm formation with secondary mineral precipitates
      of magnetite deposited as tiny globular clusters on the extra polymeric
      substances. The morphological and mineralogical changes in COB, post DIRB
      application, yielded a maximum of 68.5% nickel and 80.98% cobalt in 10 days using
      8M H2SO4.

PMID- 23972397
TI  - Rapid analysis of barley straw before and after dilute sulfuric acid pretreatment
      by photoluminescence.
AB  - The fluorescence intensities (FIs) of raw and pretreated barley straws were
      measured by fluorescence microscopy, and the difference in the fluorescence
      intensity of barley straw before and after dilute acid pretreatment was analyzed
      by investigation of the major compounds of barley straw. The difference in
      fluorescence intensity was due to the difference in xylan content. Barley straw
      was pretreated using dilute sulfuric acid at various conditions and the
      correlation between the fluorescence intensity and glucose yield of barley straw
      was investigated. The coefficient of determination (R(2)) of the correlation was
      found to be 72.28%. Also the calibration of fluorescence intensity with the xylan
      content was performed. In addition, the absorption and emission spectra of the
      raw and the pretreated barley straw were examined to verify the proposed method.
      The absorption and emission wave lengths were 550 nm and 665 nm, respectively.

PMID- 23972398
TI  - Multiplexed salivary protein profiling for patients with respiratory diseases
      using fiber-optic bundles and fluorescent antibody-based microarrays.
AB  - Over the past 40 years, the incidence and prevalence of respiratory diseases have
      increased significantly throughout the world, damaging economic productivity and
      challenging health care systems. Current diagnoses of different respiratory
      diseases generally involve invasive sampling methods such as induced sputum or
      bronchoalveolar lavage that are uncomfortable, or even painful, for the patient.
      In this paper, we present a platform incorporating fiber-optic bundles and
      antibody-based microarrays to perform multiplexed protein profiling of a panel of
      six salivary biomarkers for asthma and cystic fibrosis (CF) diagnosis. The
      platform utilizes an optical fiber bundle containing approximately 50,000
      individual 4.5 MUm diameter fibers that are chemically etched to create
      microwells in which modified microspheres decorated with monoclonal capture
      antibodies can be deposited. On the basis of a sandwich immunoassay format, the
      array quantifies human vascular endothelial growth factor (VEGF), interferon
      gamma-induced protein 10 (IP-10), interleukin-8 (IL-8), epidermal growth factor
      (EGF), matrix metalloproteinase 9 (MMP-9), and interleukin-1 beta (IL-1beta)
      salivary biomarkers in the subpicomolar range. Saliva supernatants collected from
      291 individuals (164 asthmatics, 71 CF patients, and 56 healthy controls (HC))
      were analyzed on the platform to profile each group of patients using this six
      analyte suite. It was found that four of the six proteins were observed to be
      significantly elevated (p < 0.01) in asthma and CF patients compared with HC.
      These results demonstrate the potential to use the multiplexed protein array
      platform for respiratory disease diagnosis.

PMID- 23972399
TI  - Isolation and functional analysis of denitrifiers in an aquifer with high
      potential for denitrification.
AB  - Aquifers are among the main freshwater sources. The Raigon aquifer is susceptible
      to contamination, mainly by nitrate and pesticides, such as atrazine, due to
      increasing agricultural activities in the area. The capacity of indigenous
      bacteria to attenuate nitrate contamination in different wells of this aquifer
      was assessed by measuring denitrification rates with either acetate plus
      succinate or nitrate amendments. Denitrification activity in nitrate-amended
      assays was significantly higher than in unamended assays, particularly in
      groundwater from wells where nitrate concentration was 33.5 mg L(-1) or lower.
      Furthermore, groundwater denitrifiers capable of using acetate or succinate as
      electron donors were isolated, identified by 16S rRNA gene sequencing and
      evaluated for functional denitrification genes (nirS, nirK and nosZ).
      Phylogenetic affiliation of 54 isolates showed that all members belonged to nine
      different genera within the Proteobacteria (Bosea, Ochrobactrum, Azospira,
      Zoogloea, Acidovorax, Achromobacter, Vogesella, Stenotrophomonas and
      Pseudomonas). In addition, isolate AR28 that clustered separately from validly
      described species could potentially belong to a new genus. The majority of the
      isolates were related to species belonging to previously reported denitrifying
      genera. However, the phylogeny of the nirS and nosZ genes revealed new sequences
      of these functional genes. To our knowledge, this is the first isolation and
      sequencing of the nirS gene from the genus Vogesella, as well as the nosZ gene
      from the genera Acidovorax and Zoogloea. The results indicated that indigenous
      bacteria in the Raigon aquifer had the capacity to overcome high nitrate
      contamination and exhibited functional gene diversity.

PMID- 23972400
TI  - Ferumoxtran-10 ultrasmall superparamagnetic iron oxide-enhanced diffusion
      weighted imaging magnetic resonance imaging for detection of metastases in normal
      sized lymph nodes in patients with bladder and prostate cancer: do we enter the
      era after extended pelvic lymph node dissection?

PMID- 23972401
TI  - Increased collagen accumulation in eggshell membrane after feeding with dietary
      wood charcoal powder and vinegar.
AB  - Collagen in an eggshell membrane is important for egg preservation, medical burn
      treatment and manufacturing of cosmetics. Because collagen in the membrane is
      little, it is a need to improve the accumulation in the membrane to develop these
      applications. Wood charcoal powder with vinegar (WCV) is a natural substance that
      improves poultry production. In hen fed with WCV, total collagen in the eggshell
      membrane increased with an increase in dietary WCV and significantly increased in
      the 1.0% WCV group (p < 0.05). Scanning and light microscopic images revealed
      that this group had thicker eggshell membranes and a fine mesh structure composed
      of finer and more densely distributed fibres than in the control. Eggs from WCV
      group showed slow Haugh unit decrease during egg storage and the decrease
      correlated with total collagen in eggshell membrane. In intact chicken, type I
      and type III collagens were found in different specific locations in the oviduct
      but not in the membrane. The finding that collagen accumulates in the eggshell
      membrane under WCV feeding suggests that feeding chicken with WCV will permit
      long-term storage of eggs in poultry production, and the increased volume of
      total collagen will facilitate its application in medicine and cosmetics.

PMID- 23972402
TI  - Unexpected cross-reactivity in a cat-allergy patient. An allergic reaction at the
      circus.

PMID- 23972403
TI  - Chronic urticaria in myasthenia gravis patients - more than occasional
      coexistence?

PMID- 23972404
TI  - Double-blind food challenges in children in general paediatric practice: useful
      and safe, but not without pitfalls.
AB  - OBJECTIVE: To describe results of double-blind placebo-controlled food challenges
      (DBPCFC) with cow's milk, hen's egg, soy, peanut and hazelnut in general
      paediatric practice. METHODS: Food challenges were performed between January 2006
      and June 2011, in children 0-18 years of age, on two half-day hospital admissions
      with a one-week interval. Tests were performed in a double-blind fashion
      following a standardised protocol with validated recipes. RESULTS: Overall, 234
      food challenges were performed in 209 children: 160 with cow's milk, 35 with
      peanut, 21 with hen's egg, 11 with hazelnuts, and 7 with soy. In two thirds of
      the cases, the DBPCFC was negative (cow's milk: 57.5%; peanut: 40.0%; hen's egg:
      66.7%, hazelnut: 90.9%, soy: 100%). The only patient characteristic significantly
      associated with a positive DBPCFC was the presence of symptoms from three
      different organ systems (p=0.007). Serious systemic allergic reactions with
      wheeze or anaphylaxis occurred in only two children (0.9%). Symptoms were
      recorded on 29.3% of placebo days. In 30/137 children with a negative test (22%),
      symptoms returned when reintroducing the allergen into the diet, mostly (66.7%)
      transient. Of the 85 tests regarded as positive by the attending physician, 19
      (22.4%) did not meet predefined criteria for a positive test. This was
      particularly common with non-specific symptoms. CONCLUSION: A DBPCFC can be
      safely performed in a general hospital for a range of food allergens. The test
      result is negative in most cases except for peanut. Non-specific symptoms may
      hamper the interpretation of the DBPCFC, increasing the risk of a false-positive
      result.

PMID- 23972405
TI  - Fixed drug eruption due to etoricoxibe - a case report.

PMID- 23972406
TI  - The diagnosis of common variable immunodeficiency in adults should not be missed:
      a delayed diagnosis can be devastating.

PMID- 23972407
TI  - The relation between mechanical impact parameters and most frequent bicycle
      related head injuries.
AB  - The most frequent head injuries resulting from bicycle accidents include skull
      fracture acute subdural hematoma (ASDH), cerebral contusions, and diffuse axonal
      injury (DAI). This review includes epidemiological studies, cadaver experiments,
      in vivo imaging, image processing techniques, and computer reconstructions of
      cycling accidents used to estimate the mechanical parameters leading to specific
      head injuries. The results of the head impact tests suggest the existence of an
      energy failure level for the skull fracture, specific for different impact
      regions (22-24J for the frontal site and 5-15J for temporal site). Typical linear
      patterns were described for frontal, parietal and occipital skull fracture.
      Temporal skull fracture described considerably higher variability. In term of
      contusion mechanogenesis, the experiments proved that relative brain-skull motion
      will not be prevented if the maximum frequency of the impact frequency spectrum
      stays below 150Hz or below the frequency corresponding to the impedance peak of
      the head under investigation. The brain shift patterns in humans, both in dynamic
      and quasistatic situations were shown to be very complex, with maximum amplitudes
      localized at the level of the inferolateral aspects of the frontal and temporal
      lobes. The resulting brain maximum amplitudes differed when the head was
      subjected to a sagittal or lateral motion. Finally, the presented data support
      the existence of a critical elongation/stretch criterion for the occurrence of
      ASDH due to BV rupture, located around 5mm elongation or 25% stretch limit. In
      addition, a tolerance level lying around 10,000rad/s(2) for pulse durations below
      10ms was established for BV rupture, which seems to decrease with increasing
      pulse duration. The described research indicates that injury specific tolerance
      criteria can provide a more accurate prediction for head injuries than the
      currently used HIC. Internal brain lesions are strongly related to rotational
      effects which are not appropriately accounted by the commonly accepted head
      injury criterion (HIC). The research summarized in this paper adds significantly
      to the creation of a fundamental knowledge for the improvement of bicycle helmets
      as well as other head protective measures. The described investigations and
      experimental results are of crucial importance also for forensic research. 

PMID- 23972408
TI  - Descriptive and predictive validity of somatic attributions in patients with
      somatoform disorders: a systematic review of quantitative research.
AB  - OBJECTIVE: Research on hypochondriasis and other somatoform disorders (SFD) has
      provided evidence that patients with SFD tend to attribute their symptoms to
      organic dysfunctions or disease. However, recent studies appear to discredit
      this. There is no systematic evidence on whether patients with SFD predominantly
      rely on somatic attributions, despite calls to include somatic attributions as a
      positive criterion of somatic symptom disorder (SSD) in the upcoming Diagnostic
      and Statistical Manual of Mental Disorders (DSM-5). METHODS: This study is a
      systematic review of quantitative studies which assess the descriptive and
      predictive validity of somatic attribution in SFD. The literature search was
      restricted to studies with patients who met the DSM-IV criteria for SFD. RESULTS:
      Somatic attribution style in SFD has acceptable descriptive but insufficient
      predictive validity. This confirms that the overlap between somatic and
      psychological attributions is often substantial. Attribution style can
      discriminate between SFD patients with and without comorbidity. CONCLUSION: A
      somatic attribution style does not qualify as a positive criterion in SSD.
      However, there is an urgent need for further research on causal illness
      perceptions in the full spectrum of medically unexplained symptoms in order to
      confirm this result. Given its high prevalence, research on psychological
      attribution style is warranted. Re-attribution does not provide a framework
      sophisticated enough to address the needs of patients in primary care.

PMID- 23972409
TI  - Illness perceptions, mood and quality of life: a systematic review of coronary
      heart disease patients.
AB  - OBJECTIVE: To examine published literature investigating the relationship between
      illness perceptions, mood and quality of life (QoL) in coronary heart disease
      (CHD) populations. METHODS: Key databases were systematically searched (CINAHL,
      Medline, PsycINFO, Scopus and Web of Science) for studies matching the inclusion
      criteria between November 2011 and February 2012. References of included studies
      were examined and key authors contacted. Studies were subject to a quality
      control check. RESULTS: 21 studies met the inclusion criteria. A synthesis of the
      results found that illness perceptions were correlated to and predicted QoL and
      mood across CHD diagnoses. Specific illness perceptions (control, coherence and
      timeline) were found to be important for patients that had experienced an
      unexpected medical event, such as myocardial infarction. CONCLUSION: The results
      of this study provide support that illness perceptions are related to outcomes
      across CHD populations and disease progression, however the results do not
      selectively support one particular model. Recommendations are consistent with
      cardiac rehabilitation guidelines. Further research should focus on the systemic
      impact of illness perceptions.

PMID- 23972410
TI  - Somatic symptom disorder: an important change in DSM.
AB  - This paper describes the rationale for the new diagnosis of somatic symptom
      disorder (SSD) within DSM5. SSD represents a consolidation of a number of
      previously listed diagnoses. It deemphasizes the centrality of medically
      unexplained symptoms and defines the disorder on the basis of persistent somatic
      symptoms associated with disproportionate thoughts, feelings, and behaviors
      related to these symptoms. Data are presented concerning reliability, validity,
      and prevalence of SSD, as well as tasks for future research, education, and
      clinical practice. 

PMID- 23972411
TI  - The role of goal cognitions, illness perceptions and treatment beliefs in self
      reported adherence after kidney transplantation: a cohort study.
AB  - OBJECTIVE: Nonadherence to immunosuppressive medication (IM) after kidney
      transplantation is related to poorer patient and graft outcomes; therefore
      research into modifiable factors associated with nonadherence is a priority. In
      this prospective cohort study we investigated whether changes in goal cognitions,
      illness perceptions, and treatment beliefs were related to self-reported
      medication adherence six months after kidney transplantation. METHODS: Interviews
      were conducted with patients in the out-patient clinic six weeks (T1: n=113) and
      six months (T2: n=106) after transplantation. Self-reported adherence was
      measured using the Basel Assessment of Adherence to Immunosuppressive Medications
      Scale (BAASIS(c) Interview). The Brief Illness Perceptions Questionnaire, Beliefs
      about Medicines Questionnaire and questions on goal cognitions were also
      administered at both time points. RESULTS: Self-reported nonadherence increased
      significantly between 6 weeks and 6 months after transplantation from 17% to 27%.
      Importance of medication adherence as a personal goal and self-efficacy to
      successfully carry out this goal decreased significantly over time. Perceived
      necessity of immunosuppressive medication was high but significantly decreased
      over time. Concerns about the medicines were low. There were no significant
      changes in illness perceptions or concerns over time. An increase in perceived
      graft longevity (timeline) was related to higher likelihood of nonadherence six
      months post-transplant. Furthermore, younger adult patients were more likely to
      be nonadherent six months after transplantation. CONCLUSION: The self-reported
      nonadherence levels found in this study so soon after transplantation demonstrate
      the need for early and continued intervention after kidney transplantation in
      order to maximise adherence and consequently clinical outcomes. Changes in
      (unrealistic) beliefs regarding the longevity of the graft may offer a potential
      target for intervention among nonadherent patients.

PMID- 23972412
TI  - The process of cognitive behaviour therapy for chronic fatigue syndrome: which
      changes in perpetuating cognitions and behaviour are related to a reduction in
      fatigue?
AB  - OBJECTIVE: Cognitive behaviour therapy (CBT) can significantly reduce fatigue in
      chronic fatigue syndrome (CFS), but little is known about the process of change
      taking place during CBT. Based on a recent treatment model (Wiborg et al. J Psych
      Res 2012), we examined how (changes in) cognitions and behaviour are related to
      the decrease in fatigue. METHODS: We included 183 patients meeting the US Centers
      for Disease Control criteria for CFS, aged 18 to 65 years, starting CBT. We
      measured fatigue and possible process variables before treatment; after 6, 12 and
      18 weeks; and after treatment. Possible process variables were sense of control
      over fatigue, focusing on symptoms, self-reported physical functioning, perceived
      physical activity and objective (actigraphic) physical activity. We built
      multiple regression models, explaining levels of fatigue during therapy by
      (changes in) proposed process variables. RESULTS: We observed large individual
      variation in the patterns of change in fatigue and process variables during CBT
      for CFS. Increases in the sense of control over fatigue, perceived activity and
      self-reported physical functioning, and decreases in focusing on symptoms
      explained 20 to 46% of the variance in fatigue. An increase in objective activity
      was not a process variable. CONCLUSION: A change in cognitive factors seems to be
      related to the decrease in fatigue during CBT for CFS. The pattern of change
      varies considerably between patients, but changes in process variables and
      fatigue occur mostly in the same period.

PMID- 23972413
TI  - Does neuropsychological test performance predict outcome of cognitive behavior
      therapy for Chronic Fatigue Syndrome and what is the role of underperformance?
AB  - OBJECTIVE: A subgroup of patients with Chronic Fatigue Syndrome (CFS) has
      cognitive impairments, reflected by deviant neuropsychological test performance.
      However, abnormal test scores can also be caused by suboptimal effort. We
      hypothesized that worse neuropsychological test performance and underperformance
      were related to each other and to a smaller reduction in fatigue, functional
      impairments, physical limitations and higher dropout rates following cognitive
      behavior therapy (CBT) for CFS. METHODS: Data were drawn from a previous trial,
      in which CFS patients were randomized to two conditions; 1) guided self
      instruction and additional CBT (n=84) or 2) waiting period followed by regular
      CBT for CFS (n=85). Underperformance was assessed using the Amsterdam Short Term
      Memory Test (<84). To test neuropsychological test performance, the Symbol Digit
      Modalities Task, a simple reaction time task and a choice reaction time task were
      used. Interaction effects were determined between underperformance and
      neuropsychological test performance on therapy outcomes. RESULTS:
      Underperformance was associated to worse neuropsychological test performance, but
      there were no significant interaction effects of these two factors by therapy on
      fatigue severity, functional impairments and physical limitations, but there was
      a significant main effect of underperformance on functional impairments, physical
      limitations and dropout rates. CONCLUSION: Underperformance or neuropsychological
      test performance was not related to the change in fatigue, functional
      impairments, and physical limitations following CBT for CFS. However,
      underperforming patients did drop out more often. Therapists should pay attention
      to beliefs and behavioral or environmental factors that might maintain
      underperformance and increase the risk of dropout.

PMID- 23972414
TI  - Differences in physical functioning between relatively active and passive
      patients with Chronic Fatigue Syndrome.
AB  - OBJECTIVE: According to the Cognitive behavioral therapy (CBT) protocol for
      patients with Chronic Fatigue Syndrome (CFS), therapists are advised to
      categorize patients in relatively active and passive patients. However, evidence
      to support the differences in physical functioning between these subgroups is
      limited. Using the baseline data from a multicentre randomized controlled trial
      (FatiGo), the differences in actual and perceived physical functioning between
      active and passive patients with CFS were evaluated. METHODS: Sixty patients, who
      received CBT during the FatiGo trial were included. Based on the expert opinion
      and using the definitions of subgroups defined in the CBT protocols, the
      therapist categorized the patient. Data from an activity monitor was used to
      calculate actual physical functioning, physical activity, daily uptime, activity
      fluctuations and duration of rest during daily life. Perceived physical
      functioning was assessed by measuring physical activity, physical functioning and
      functional impairment with the Checklist Individual Strength, Short Form-36 and
      Sickness-Impact Profile 8. RESULTS: Relatively active patients have a
      significantly higher daily uptime and show significantly less fluctuations in
      activities between days. Passive patients experience a significantly lower level
      of physical functioning and feel more functionally impaired in their mobility.
      However, no significant differences were found in the other actual or perceived
      physical functioning indices. CONCLUSIONS: A clear difference in actual and
      perceived physical functioning between relatively active and passive patients
      with CFS as judged by their therapists could not be found. Future research is
      needed to form a consensus on how to categorize subgroups of patients with CFS.

PMID- 23972415
TI  - Feedback on patient progress and clinical support tools for therapists: improved
      outcome for patients at risk of treatment failure in psychosomatic in-patient
      therapy under the conditions of routine practice.
AB  - OBJECTIVES: Although psychosomatic in-patient treatment is effective, 5-10% of
      the patients deteriorate. Providing patient progress feedback and clinical
      support tools to therapists improves the outcome for patients at risk of
      deterioration in counseling, outpatient psychotherapy, and substance abuse
      treatment. This study investigated the effects of feedback on psychosomatically
      treated in-patients at risk of treatment failure. METHODS: At intake, all
      patients of two psychosomatic clinics were randomized either into the
      experimental group or the treatment-as-usual control group. Both groups were
      tracked weekly with the "Outcome Questionnaire" (OQ-45) measuring patient
      progress and with the clinical support tool "Assessment of Signal Cases" (ASC).
      Therapists received feedback from both instruments for all their experimental
      group patients. "Patients at risk" were defined as patients who deviated from
      expected recovery curves by at least one standard deviation. Of 252 patients, 43
      patients were at risk: 23 belonged to the experimental group, 20 to the control
      group. The feedback effect was analyzed using a level-2-model for discontinuous
      change, effect size (d), reliable change index (RCI), and odds ratio for reliable
      deterioration. RESULTS: For patients at risk, the experimental group showed an
      improved outcome on the OQ-45 total scale compared to the control group (p<0.05,
      d=0.54). By providing feedback, the rate of reliably deteriorated patients at
      risk was reduced from 25.0% (control group) to 8.7% (experimental group) - odds
      ratio=0.29. All reliably improved patients at risk belonged to the experimental
      group. CONCLUSION: Feedback improves the outcome of patients at risk undergoing
      psychosomatic in-patient treatment.

PMID- 23972416
TI  - The metabolic costs of hostility in healthy adult men and women: cross-sectional
      and prospective analyses.
AB  - BACKGROUND: Hostility is associated with altered metabolic activity but little
      research has examined sex and/or age differences using a global index of
      metabolic dysfunction or examined different aspects of hostility. METHODS: The
      moderating effect of sex and age on the associations between three aspects of
      hostility (cynical attitude, angry affect, quarrelsome behavior in daily living)
      and metabolic burden (number of metabolic parameters in the higher quartile) were
      evaluated in 188 healthy men and women (M(age)=41; SD=11.34). Three years later,
      metabolic burden was measured again in 133 participants. RESULTS: At study onset,
      quarrelsome behavior was associated with greater metabolic burden in men and
      women (Beta=.144; p<.05). After 3 yrs, cynical hostility predicted increased
      metabolic burden among mid-age and older individuals (b=.013 and .046
      respectively; p<.001). CONCLUSION: The aspect of hostility that is most closely
      associated with metabolic burden depends on the age of the participants and
      whether measures are concurrent or prospective.

PMID- 23972417
TI  - Increased risk of hyperlipidemia in patients with major depressive disorder: a
      population-based study.
AB  - OBJECTIVE: We conducted this study to examine the prevalence and incidence of
      hyperlipidemia among Taiwanese patients with major depressive disorder (MDD).
      METHODS: We used a random sample of 766,427 subjects who were >= 18 years old in
      2005. Subjects with at least one primary diagnosis of MDD were identified.
      Individuals with a primary or secondary diagnosis of hyperlipidemia or medication
      treatment for hyperlipidemia were also identified. We compared the prevalence of
      hyperlipidemia in MDD patients with the general population in 2005. We followed
      this cohort from 2006 to 2010 to detect incident cases of hyperlipidemia in MDD
      patients compared with the general population. RESULTS: The prevalence of
      hyperlipidemia in patients with MDD was higher than in the general population
      (14.4% vs. 7.9%, odds ratio 1.67; 95% confidence interval, 1.53-1.82) in 2005.
      The average annual incidence of hyperlipidemia in patients with MDD was also
      higher than in the general population (3.62% vs. 2.55%, risk ratio 1.35; 95%
      confidence interval, 1.24-1.47) from 2006 to 2010. Higher incidence of
      hyperlipidemia was associated with MDD group, increased age, diabetes,
      hypertension, and higher socioeconomic status. CONCLUSIONS: Patients with MDD had
      a higher prevalence and incidence of hyperlipidemia compared with the general
      population. Younger MDD patients and MDD patients with first-generation
      antipsychotic exposure or antidepressant exposure had an increased risk of
      hyperlipidemia compared with individuals in the general population.

PMID- 23972419
TI  - Associations of psychological thriving with coping efficacy, expectations for
      future growth, and depressive symptoms over time in people with arthritis.
AB  - OBJECTIVE: Psychological thriving reflects a trajectory of growth over time as
      opposed to scaling back expectations. Whether thriving is a product, precursor,
      or process of coping with arthritis-related limitations is unclear. We examined
      associations between thriving, coping efficacy, and expectations for future
      growth in individuals with arthritis, and the relations of thriving to depressive
      symptoms and retrospective perceptions of personal growth over a six-month
      period. METHODS: A sample of 423 people with arthritis completed measures of
      thriving, coping efficacy, depressive symptoms, and expectations for future
      growth; 168 individuals completed a six-month follow-up survey. Structural
      equation modeling analyses compared three possible models of psychological
      thriving, controlling for disease-related variables. Hierarchical regression
      analyses of the cross-lagged associations of thriving with retrospective
      perceptions of positive personal change and depressive symptoms were also
      conducted. RESULTS: Structural equation analyses suggest that the process model
      in which thriving and coping efficacy jointly predicted expectations for future
      growth best fit the data. Baseline thriving was also associated with
      retrospective perceptions of personal growth at follow-up and fewer depressive
      symptoms at baseline and follow-up, after controlling for disease-related
      variables. CONCLUSION: Overall, these findings suggest that psychological
      thriving is synergistically related to coping efficacy, and to expectations for
      future growth and less depression, in people with arthritis. Importantly, our
      findings support the notion that psychological thriving is more than scaling back
      expectations, and that thriving may be an important quality to cultivate to
      address the burden of depression in people with arthritis.

PMID- 23972418
TI  - Diabetes and life-long cognitive ability.
AB  - OBJECTIVES: There is a widespread consensus that diabetes impairs cognitive
      functioning. However, some recent findings have shown that many health conditions
      generally thought to be detrimental to cognitive functioning are in fact linked
      to pre-morbid cognitive ability, suggesting reverse causation. To better
      understand the causality in diabetes-cognition relationship, this study
      investigates the association of older-age diabetes with concurrent and childhood
      cognitive functioning. METHODS: Lothian Birth Cohort 1936 participants (N=1017)
      completed the same general cognitive ability test at ages 11 and 70 years. Scores
      were compared between those with and without diabetes at age 70. Diabetes status
      was based on self-reports and haemoglobin A1c levels. RESULTS: People with
      diabetes had lower mean cognitive ability scores at ages 11 and 70 when compared
      with those without diabetes. The effect size was roughly similar at both ages
      (Cohen's d~0.32). When adjusted for age-11 cognitive ability, diabetes status was
      not associated with cognitive ability at age 70. The association between
      childhood cognitive ability and older-age diabetes was partly accounted for by
      body mass index and cholesterol level in older-age. CONCLUSION: In this sample,
      diabetes was associated with poorer cognitive ability in old age but this was
      because of life-long lower cognitive ability in people with diabetes instead of
      diabetes impairing cognitive functioning.

PMID- 23972420
TI  - General anxiety symptoms after acute lung injury: predictors and correlates.
AB  - OBJECTIVE: Acute lung injury (ALI) is common in the intensive care unit (ICU),
      typically requiring life support ventilation. Survivors often experience anxiety
      after hospital discharge. We evaluated general anxiety symptoms 3 months after
      ALI for: (1) associations with patient characteristics and ICU variables, and (2)
      cross-sectional associations with physical function and quality of life (QOL).
      METHODS: General anxiety was assessed as part of a prospective cohort study
      recruiting patients from 13 ICUs at four hospitals in Baltimore, MD using the
      Hospital Anxiety and Depression Scale--Anxiety Subscale (HAD-A), with
      associations evaluated using multivariable linear and logistic regression models.
      RESULTS: Of 152 patients, 38% had a positive screening test for general anxiety
      (HAD-A>=8). Pre-ICU body mass index and psychiatric comorbidity were associated
      with general anxiety (OR, 95% confidence interval (CI): 1.06 (1.00, 1.13) and
      3.59 (1.25, 10.30), respectively). No ICU-related variables were associated with
      general anxiety. General anxiety was associated with the number of instrumental
      ADL dependencies (Spearman's rho=0.22; p=0.004) and worse overall QOL as measured
      by EQ-5D visual analog scale (VAS) (rho=-0.34; p<0.001) and utility score (rho=
      0.30; p<0.001), and by the SF-36 mental health domain (rho=-0.70; p<0.001) and
      Mental Component Summary score (rho=-0.73; p<0.001). CONCLUSION: Many patients
      have substantial general anxiety symptoms 3 months after ALI. General anxiety was
      associated with patient characteristics and impaired physical function and
      quality of life. Early identification and treatment of general anxiety may
      enhance physical and emotional function in patients surviving critical illnesses.

PMID- 23972421
TI  - A commentary on 'The effects of identification with a support group on the mental
      health of people with multiple sclerosis'.

PMID- 23972422
TI  - A reply to Gallagher, O'Donnell, Minescu, & Muldoon's commentary on 'The effects
      of identification with a support group on the mental health of people with
      multiple sclerosis'.

PMID- 23972423
TI  - Systemic lupus erythematosus and other autoimmune rheumatic diseases: challenges
      to treatment.
AB  - Increased understanding of the molecular mechanisms underlying the pathogenenesis
      of autoimmune rheumatic diseases has led to targeted biological treatments that
      modulate various aspects of the immune response. These new treatments, together
      with more judicious use of other immunosuppressive drugs, have resulted in marked
      improvements in morbidity and mortality. Although belimumab, an agent that
      inhibits B-cell survival, is the first drug to be approved by the US Food and
      Drug Administration for the treatment of systemic lupus erythematosus in 50
      years, many other immunological targets are under investigation. We discuss the
      recent advances in the biological treatment of autoimmune rheumatic diseases,
      with a particular focus on systemic lupus erythematosus. 

PMID- 23972424
TI  - Association of pulmonary conduit type and size with durability in infants and
      young children.
AB  - BACKGROUND: Treatment of congenital heart disease may include placement of a
      right ventricle to pulmonary artery conduit that requires future surgical
      replacement. We sought to identify surgeon-modifiable factors associated with
      durability (defined as freedom from surgical replacement or explantation) of the
      initial conduit in children less than 2 years of age at initial insertion.
      METHODS: Since 2002, 429 infants were discharged from 24 Congenital Heart
      Surgeons' Society member institutions after initial conduit insertion. Parametric
      hazard analysis identified factors associated with conduit durability while
      adjusting for patient characteristics, the institution where the conduit was
      inserted, and time-dependent interval procedures performed after conduit
      insertion but before replacement/explantation. RESULTS: In all, 138 conduit
      replacements (32%) and 3 explantations (1%) were performed. Conduit durability at
      a median follow-up of 6.0 years (range, 0.1 to 11.7) was 63%. After adjusting for
      interval procedures and institution, placement of a conduit with smaller z-score
      was associated with earlier replacement/explantation (p = 0.002). Moreover,
      conduit durability was substantially reduced with aortic allografts (p = 0.002)
      and pulmonary allografts (p = 0.03) compared with bovine jugular venous valved
      conduits (JVVC). The JVVC were 12 mm to 22 mm in diameter at insertion (compared
      with 6 mm to 20 mm for allografts); therefore, a parametric propensity-adjusted
      analysis of patients with aortic or pulmonary allografts versus JVVC with
      diameter of 12 mm or greater was performed, which verified the superior
      durability of JVVC. CONCLUSIONS: Pulmonary conduit type and z-score are
      associated with late conduit durability independent of the effects of institution
      and subsequent interval procedures. Surgeons can improve long-term conduit
      durability by judiciously oversizing, and by selecting a JVVC.

PMID- 23972425
TI  - The accelerated atherogenesis of venous grafts might be attributed to aggravated
      concentration polarization of low density lipoproteins: a numerical study.
AB  - We hypothesize that after implantation the much elevated water filtration rate of
      venous grafts may cause aggravated concentration polarization of low density
      lipoproteins (LDLs), in turn lead to the accelerated atherogenesis of the grafts.
      To verify the hypothesis, we numerically simulated the transport of LDLs in
      various models of arterial bypasses with different grafts (veins or arteries) and
      geometrical configurations. The results showed that the venous grafts might
      endure abnormally high lipid infiltration/accumulation within the vessel wall due
      to severely elevated luminal surface LDL concentration. When compared to the
      conventional bypass models, the S-type bypass had the lowest luminal surface LDL
      concentration along its host artery floor, but the highest degree of risk to
      develop atherosclerotic lesions in its venous graft. Among the three conventional
      bypass models, the one with 30 degrees  anastomosis had the lowest risk to
      develop atherosclerosis in the venous graft. In conclusion, when compared with
      the bypass models with arterial grafts, the venous bypass models had rather high
      levels of LDL concentration polarization (cw) in the vein grafts, especially at
      the early stages of implantation. This might result in high
      infiltration/accumulation of LDLs within the walls of the venous grafts, leading
      to a fast genesis/development of atherosclerosis there. 

PMID- 23972426
TI  - New gene responsible for para-aminobenzoate biosynthesis.
AB  - Folate is an essential cofactor in all living cells for one-carbon transfer
      reactions. para-Aminobenzoate (pABA), a building block of folate, is usually
      derived from chorismate in the shikimate pathway by reactions of
      aminodeoxychorismate synthase (PabA and -B) and 4-amino-4-deoxychorismate lyase
      (PabC). We previously suggested that an alternative pathway for pABA biosynthesis
      would operate in some microorganisms such as Lactobacillus fermentum and
      Nitrosomonas europaea since these bacteria showed a prototrophic phenotype to
      pABA despite the fact that there are no orthologs of pabA, -B, and -C in their
      genome databases. In this study, a gene of unknown function, NE1434, was obtained
      from N. europaea by shotgun cloning using a pABA-auxotrophic Escherichia coli
      mutant (DeltapabABC) as a host. A tracer experiment using [U-(13)C6]glucose
      suggested that pABA was de novo synthesized in the transformant. An E. coli
      DeltapabABCDeltaaroB mutant carrying the NE1434 gene exhibited a prototrophic
      phenotype to pABA, suggesting that compounds in the shikimate pathway including
      chorismate were not utilized as substrates by NE1434. Moreover, the CT610 gene,
      an ortholog of NE1434 located in the folate biosynthetic gene cluster in
      Chlamydia trachomatis, also complemented pABA-auxotrophic E. coli mutants. Taken
      together, these results suggest that NE1434 and CT610 participate in pABA
      biosynthesis. 

PMID- 23972427
TI  - Recommendations for tool-handle material choice based on finite element analysis.
AB  - Huge areas of work are still done manually and require the usages of different
      powered and non-powered hand tools. In order to increase the user performance,
      satisfaction, and lower the risk of acute and cumulative trauma disorders,
      several researchers have investigated the sizes and shapes of tool-handles.
      However, only a few authors have investigated tool-handles' materials for further
      optimising them. Therefore, as presented in this paper, we have utilised a finite
      element method for simulating human fingertip whilst grasping tool-handles. We
      modelled and simulated steel and ethylene propylene diene monomer (EPDM) rubber
      as homogeneous tool-handle materials and two composites consisting of EPDM rubber
      and EPDM foam, and also EPDM rubber and PU foam. The simulated finger force was
      set to obtain characteristic contact pressures of 20 kPa, 40 kPa, 80 kPa, and 100
      kPa. Numerical tests have shown that EPDM rubber lowers the contact pressure just
      slightly. On the other hand, both composites showed significant reduction in
      contact pressure that could lower the risks of acute and cumulative trauma
      disorders which are pressure-dependent. Based on the results, it is also evident
      that a composite containing PU foam with a more evident and flat plateau deformed
      less at lower strain rates and deformed more when the plateau was reached, in
      comparison to the composite with EPDM foam. It was shown that hyper-elastic foam
      materials, which take into account the non-linear behaviour of fingertip soft
      tissue, can lower the contact pressure whilst maintaining low deformation rate of
      the tool-handle material for maintaining sufficient rate of stability of the hand
      tool in the hands. Lower contact pressure also lowers the risk of acute and
      cumulative trauma disorders, and increases comfort whilst maintaining
      performance. 

PMID- 23972428
TI  - Solid-state NMR concepts for the investigation of supported transition metal
      catalysts and nanoparticles.
AB  - In recent years, solid-state NMR spectroscopy has evolved into an important
      characterization tool for the study of solid catalysts and chemical processes on
      their surface. This interest is mainly triggered by the need of environmentally
      benign organic transformations ("green chemistry"), which has resulted in a large
      number of new catalytically active hybrid materials, which are organized on the
      meso- and nanoscale. Typical examples of these catalysts are supported
      homogeneous transition metal catalysts or transition metal nanoparticles (MNPs).
      Solid-state NMR spectroscopy is able to characterize both the structures of these
      materials and the chemical processes on the catalytic surface. This article
      presents recent trends both on the characterization of immobilized homogeneous
      transition metal catalysts and on the characterization of surface species on
      transition metal surfaces. 

PMID- 23972429
TI  - Finite element analysis and computed tomography based structural rigidity
      analysis of rat tibia with simulated lytic defects.
AB  - Finite element analysis (FEA), CT based structural rigidity analysis (CTRA) and
      mechanical testing is performed to assess the compressive failure load of rat
      tibia with simulated lytic defects. Twenty rat tibia were randomly assigned to
      four equal groups (n=5). Three of the groups included a simulated defect at
      various locations: anterior bone surface (Group 1), posterior bone surface (Group
      2) and through bone defect (Group 3). The fourth group was a control group with
      no defect (Group 4). Microcomputed tomography was used to assess bone structural
      rigidity properties and to provide 3D model data for generation of the finite
      element models for each specimen. Compressive failure load calculated using CT
      derived rigidity parameters (FCTRA) was well correlated to failure load recorded
      in mechanical testing (R(2)=0.96). The relationships between mechanical testing
      failure load and the axial rigidity (R(2)=0.61), bending rigidity (R(2)=0.71) and
      FEA calculated failure loads, considering bone as an elastic isotropic
      (R(2)=0.75) and elastic transversely isotropic (R(2)=0.90) are also well
      correlated. CTRA stress, calculated adjacent to the defect, were also shown to be
      well correlated with yield stresses calculated using the minimum density at the
      weakest cross section (R(2)=0.72). No statistically significant relationship
      between apparent density and mechanical testing failure load was found (P=0.37).
      In summary, the results of this study indicate that CTRA analysis of bone
      strength correlates well with both FEA and results obtained from compression
      experiments. In addition there exist a good correlation between structural
      rigidity parameters and experimental failure loads. In contrast, there was no
      correlation between average bone density and failure load. 

PMID- 23972430
TI  - A novel approach to estimate trabecular bone anisotropy using a database
      approach.
AB  - Continuum finite element (FE) models of bones have become a standard pre-clinical
      tool to estimate bone strength. These models are usually based on clinical CT
      scans and material properties assigned are chosen as isotropic based only on the
      density distribution. It has been shown, however, that trabecular bone elastic
      behavior is best described as orthotropic. Unfortunately, the use of orthotropic
      models in FE analysis derived from CT scans is hampered by the fact that the
      measurement of a trabecular orientation (fabric) is not possible from clinical CT
      images due to the low resolution of such images. In this study, we explore the
      concept of using a database (DB) of high-resolution bone models to derive the
      fabric information that is missing in clinical images. The goal of this study was
      to investigate if models with fabric derived from a relatively small database can
      already produce more accurate results than isotropic models. A DB of 33 human
      proximal femurs was generated from micro-CT scans with a nominal isotropic
      resolution of 82 um. Continuum FE models were generated from the images using a
      pre-defined mesh template in combination with an iso-anatomic mesh morphing tool.
      Each element within the mesh template is at a specific anatomical location. For
      each element within the cancellous bone, a spherical region around the element
      centroid with a radius of 2mm was defined. Bone volume fraction and the mean
      intercept-length fabric tensor were analyzed for that region. Ten femurs were
      used as test cases. For each test femur, four different models were generated:
      (1) an orthotropic model based on micro-CT fabric measurements (gold standard),
      (2) an orthotropic model based on the fabric derived from the best-matched
      database model, (3) an isotropic-I model in which the fabric tensor was set to
      the identity tensor, and (4) a second isotropic-II model with its total bone
      stiffness fitted to the gold standard. An elastic-plastic damage model was used
      to simulate failure and post failure behavior during a fall to the side. The
      results show that all models produce a similar stress distribution. However,
      compared to the gold standard, both isotropic-I and II models underestimated the
      stress/damage distributions significantly. We found no significant difference
      between DB-derived and gold standard models. Compared to the gold standard, the
      isotropic-I models further underestimated whole bone stiffness by 26.3% and
      ultimate load by 14.5%, while these differences for the DB-derived orthotropic
      models were only 4.9% and 3.1% respectively. The results indicate that the
      concept of using a DB to estimate patient-specific anisotropic material
      properties can considerably improve the results. We expect that this approach can
      lead to more accurate results in particular for cases where bone anisotropy plays
      an important role, such as in osteoporotic patients and around implants.

PMID- 23972431
TI  - Finite element analysis of retroacetabular osteolytic defects following total hip
      replacement.
AB  - Periprosthetic osteolysis in the retroacetabular region with cancellous bone loss
      is a recognized phenomenon in the long-term follow-up of total hip replacement.
      The effects on load transfer in the presence of defects are less well known. A
      finite element model incorporating a retroacetabular defect behind a cementless
      component was validated against a 4th generation sawbone pelvis. Computational
      predictions of surface strain and von Mises stresses were closely correlated to
      experimental findings. The presence of a cancellous defect increased von Mises
      stress in the cortical bone of the medial wall of the pelvis. At a load of 600 N
      this was under the predicted failure stress for cortical bone. Increases in the
      cup size relative to the acetabulum caused increased stress in the cortical bone
      of the lateral wall of the pelvis, adjacent to the acetabulum. We are confident
      that our modeling approach can be applied to patient specific defects to predict
      pelvis stress with large loads and a range of activities.

PMID- 23972432
TI  - Model-based approach for human kinematics reconstruction from markerless and
      marker-based motion analysis systems.
AB  - Modeling tools related to the musculoskeletal system have been previously
      developed. However, the integration of the real underlying functional joint
      behavior is lacking and therefore available kinematic models do not reasonably
      replicate individual human motion. In order to improve our understanding of the
      relationships between muscle behavior, i.e. excursion and motion data, modeling
      tools must guarantee that the model of joint kinematics is correctly validated to
      ensure meaningful muscle behavior interpretation. This paper presents a model
      based method that allows fusing accurate joint kinematic information with motion
      analysis data collected using either marker-based stereophotogrammetry (MBS)
      (i.e. bone displacement collected from reflective markers fixed on the subject's
      skin) or markerless single-camera (MLS) hardware. This paper describes a model
      based approach (MBA) for human motion data reconstruction by a scalable
      registration method for combining joint physiological kinematics with limb
      segment poses. The presented results and kinematics analysis show that model
      based MBS and MLS methods lead to physiologically-acceptable human kinematics.
      The proposed method is therefore available for further exploitation of the
      underlying model that can then be used for further modeling, the quality of which
      will depend on the underlying kinematic model. 

PMID- 23972433
TI  - Do stress-whitening and optical clearing of collagenous tissue occur by the same
      mechanism?
AB  - Bone is biphasic with an organic matrix and an inorganic mineral component. As we
      age bone's susceptibility to fracture increases. It has been shown that there is
      no change in mean mineralization with aging, but bone nevertheless becomes less
      tough. This aging effect is therefore likely related to the organic phase. Under
      mechanical loading, immediately prior to failure, bone has been observed to
      visually become more opaque and has been termed stress-whitening. Stress
      whitening is known to make materials tougher. The goal of this investigation was
      to investigate stress-whitening in the collagenous matrix of bone. Hydrogen bonds
      play a key role in collagen stability and we hypothesize that changes in hydrogen
      bonding will significantly affect matrix stiffness, toughness and stress
      whitening. Demineralized bone specimens were loaded in tension and stress
      whitening was monitored. The effect of hydrogen bonding on mechanical properties
      and stress-whitening process was probed by altering the Hansen's hydrogen bonding
      parameter (deltah) of the immersing solution. The Hansen's hydrogen bonding
      parameter of the immersing fluid affected the morphology, mechanical properties
      and stress whitening of specimens. Specimens were visually whiter in the absence
      of mechanical load in low deltah solvents (the specimens solvent-whitened). Both
      the observed stress-whitening and solvent-whitening were reversible and
      repeatable processes. The observed solvent-whitening that occurred without the
      presence of load was consistent with solvent-induced optical clearing (the
      opposite of whitening) in skin caused by collagen fibril swelling. Stress
      whitening and solvent whitening can be explained by a common mechanism, collagen
      fibril densification and thinning, leading to an increased distinction between
      the collagen fibrillar phase and immersing fluid, ultimately leading to more
      scattering. Bones may be at a greater risk for fracture as we age because
      solubility of the matrix changes, thus making the collagen less hydrated (and
      more brittle) even in the same solvent. 

PMID- 23972434
TI  - Reply to letter to the editor: "Computational modelling of hydrocephalus".

PMID- 23972435
TI  - A quantitative method for evaluating local perfusion using indocyanine green
      fluorescence imaging.
AB  - BACKGROUND: The purpose of this study is to introduce a new method, indocyanine
      green fluorescence imaging (ICG-FI), as an adjunct to distal pressure
      measurements in patients with peripheral arterial disease and symptomatic lower
      limb ischemia. METHODS: A total of 34 patients with peripheral arterial disease,
      including 11 with claudication (Fontaine II), 7 with rest pain (FIII), and 16
      with an ulcer or gangrene (FIV), were enrolled. After an intravenous injection of
      ICG (0.1 mg/kg), foot perfusion was recorded by an infrared light camera.
      Fluorescence intensity was plotted on a time-intensity curve using recorded
      images, allowing the calculation of new parameters. Severity of ischemia was
      assessed as the duration between the rising point and half value of maximum
      brightness (T1/2). The difference in the fluorescence intensity between 10
      seconds after the rising point and baseline (PDE10) was compared with the
      transcutaneous oxygen pressure (tcPO2) at the same site (n=51). RESULTS: Median
      T1/2 was 23 seconds in FII, 41 seconds in FIII (P<0.05), and 17 seconds in FIV
      patients. PDE10 correlated moderately with tcpO2 (r2=0.5). A cut-off value
      (PDE10=28) predicted a critically ischemic limb (FIII and FIV), defined as
      tcpO2<30 mm Hg with a sensitivity of 100% and specificity of 86.6%. CONCLUSIONS:
      Local tissue perfusion can be quantitatively evaluated by using ICG fluorescence
      imaging. It is a safe, fast, noncontact method of imaging, which may be useful
      even at the ulcer itself and in the circumferential area.

PMID- 23972436
TI  - In-hospital efficacy of endovascular aortic repair in patients with impending
      rupture versus contained rupture of abdominal aortic aneurysms.
AB  - BACKGROUND: The purpose of our study was to compare the efficacy of endovascular
      aortic repair (EVAR) in patients with impending rupture of abdominal aortic
      aneurysm (IRAAA) versus contained rupture of abdominal aortic aneurysm (CRAAA).
      METHODS: Of the 21 patients who underwent EVAR for infrarenal AAA from January
      2009 to May 2011, 11 did so for IRAAA and 10 for CRAAA. We compared their
      demographic and aneurysmal characteristics, comorbidities, complications, and
      clinical outcomes during hospitalization. RESULTS: The CRAAA group was younger
      than the IRAAA group. There were no group differences in AAA size, operation
      time, volume of contrast agent, length of hospital stay (LOHS), or preoperative
      LOHS. A small difference in mean intraoperative blood loss of ~4 mL was noted,
      but was recognized as clinically insignificant. ICU stay and postoperative LOHS
      were greater in the CRAAA than in the IRAAA. One patient in the IRAAA group had a
      mild headache after EVAR. Four patients in the CRAAA group had postoperative
      complications: 1 had acute renal dysfunction; 1 had retroperitoneal infection; 1
      had respiratory failure and myocardial infarction; and 1 died of respiratory
      tract infection and respiratory and cardiac failure. CONCLUSIONS: Patients
      undergoing EVAR for CRAAA have a higher incidence of postprocedural severe
      complications and death than patients undergoing EVAR for IRAAA.

PMID- 23972438
TI  - Data-driven sample size determination for metabolic phenotyping studies.
AB  - Sample size determination is a key question in the experimental design of medical
      studies. The number of patients to include in a clinical study is actually
      critical to evaluate costs and inclusion requirements to achieve a sufficient
      statistical power of test and the identification of significant variations among
      the factors under study. Metabolic phenotyping is an expanding field of
      translational research in medicine, focusing on the identification of metabolism
      rearrangements due to various pathophysiological conditions. This top-down
      hypothesis-free approach uses analytical chemistry methods, coupled to
      statistical analysis, to quantify subtle and coordinated metabolite concentration
      variations and eventually identify candidate biomarkers. The sample size
      determination in metabolic phenotyping studies is difficult considering the
      absence of a priori metabolic target. This technical note introduces a data
      driven sample size determination for metabolic phenotyping studies. Starting from
      nuclear magnetic resonance (NMR) spectra belonging to a small cohort, metabolic
      NMR variables are identified by the statistical recoupling of variables (SRV)
      procedure. A larger data set is then generated on the basis of Kernel density
      estimation of SRV variable distributions. Statistically significant variations of
      metabolic NMR signals identified by SRV are assessed by the Benjamini-Yekutieli
      correction for simulated data sets of variable sizes. Simulated model robustness
      is evaluated by receiver operating characteristic analysis (sensitivity and
      specificity) on an independent cohort and cross-validation. Sample size
      determination is obtained by identifying the optimal data set size, depending on
      the purpose of the study: at least one statistically significant variation
      (biomarker discovery) or a maximum of statistically significant variations
      (metabolic exploration). 

PMID- 23972437
TI  - External support of a polytetrafluoroethylene graft improves patency for bypass
      to below-knee arteries.
AB  - BACKGROUND: Patency and limb salvage after synthetic bypass to the arteries below
      the knee are inferior to that which can be achieved with autologous vein. The use
      of external support of synthetic polytetrafluoroethylene (PTFE) grafts to the
      below-knee position has been suggested to improve patency and limb salvage, a
      problem analyzed in this randomized clinical trial. We examined whether external
      graft support improves patency and/or limb salvage in patients undergoing
      reconstruction with synthetic PTFE grafts to the below-knee arteries. METHODS:
      Three hundred thirty-four patients with critical limb ischemia undergoing PTFE
      bypass to below-knee arteries were randomly assigned to have an ordinary PTFE
      graft or one with external support. Follow-up was scheduled until amputation,
      death, or at most 5 years, whichever event occurred first. RESULTS: Patients in
      both the femoropopliteal and femorodistal groups were randomized to have an
      externally supported PTFE graft (101/195 patients in the femoropopliteal group
      and 72/139 patients in the femorodistal group). Follow-up information was
      available for 329 of 334 randomized patients (99%). At 1 year postprocedure,
      primary patency for below-knee bypass was 0.55 (95% confidence interval [CI],
      0.47-0.64) with and 0.42 (95% CI, 0.34-0.50) without externally supported PTFE
      grafts, and secondary patency was 0.58 (95% CI, 0.51-0.67) and 0.47 (95% CI, 0.39
      0.56), respectively. The corresponding figures for limb salvage were 0.75 (95%
      CI, 0.68-0.82) and 0.69 (95% CI, 0.62-0.77), respectively. The log rank test
      revealed statistically significant differences between patients with or without
      externally supported grafts for patency (primary patency: chi2=4.2 [degrees of
      freedom=1; P=0.041]; secondary patency: chi2=4.3 [degrees of freedom=1; P=0.037])
      but not for limb salvage (limb salvage: chi2=0.2 [degrees of freedom=1;
      P=0.657]). CONCLUSIONS: External support to a PTFE graft used for bypass to below
      knee arteries improves primary and secondary patency but not limb salvage.

PMID- 23972439
TI  - Analogues of the Inhoffen-Lythgoe diol with anti-proliferative activity.
AB  - The anti-proliferative activity of a series of ester- and amide-linked Inhoffen
      Lythgoe side chain analogues is reported. Whereas the Inhoffen-Lythgoe diol was
      inactive in these studies, a number of aromatic and aliphatic ester-linked side
      chains demonstrated modest in vitro growth inhibition in two human cancepar cell
      lines, U87MG (glioblastoma) and HT-29 (colorectal adenocarcinoma). Structure
      activity relationship (SAR) studies demonstrated the most active aromatic (13)
      and aliphatic (25 and 29) substituted analogues were approximately equipotent in
      U87MG and HT-29 cells. Further evaluation of 13, 25, and 29 indicated these
      analogues do not activate canonical vitamin D signaling nor antagonize Hedgehog
      (Hh) signaling. Thus, the cellular mechanism(s) that govern the anti
      proliferative activity for this class of truncated vitamin D-based structures
      appears to be different from classical mechanisms previously identified for these
      scaffolds. 

PMID- 23972440
TI  - Optimization of anti-proliferative activity using a screening approach with a
      series of bis-heterocyclic G-quadruplex ligands.
AB  - Using a phenotypic screening and SAR optimization approach, a phenyl-bis-oxazole
      derivative has been identified with anti-proliferative activity, optimized with
      the use of a panel of cancer cell lines. The lead compound was synthesized by
      means of a short and effective two-step synthesis using Pd-catalyzed direct
      arylation. The compound stabilizes several quadruplex DNA sequences including a
      human telomeric DNA and one from the promoter of the HSP90 gene, although the
      structure-activity relationships of the series are not obviously related to the
      quadruplex binding. 

PMID- 23972441
TI  - Novel tetrahydropyran analogs as dipeptidyl peptidase IV inhibitors: Profile of
      clinical candidate (2R,3S,5R)-2- (2,5-difluorophenyl)-5-(4,6-dihydropyrrolo [3,4
      c]pyrazol-5-(1H)-yl)tetrahydro-2H-pyran-3-amine (23) [corrected].
AB  - A series of novel tri-2,3,5-substituted tetrahydropyran analogs were synthesized
      and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment
      of type 2 diabetes. Optimization of the series provided inhibitors with good DPP
      4 potency and selectivity over other peptidases (QPP, DPP8, and FAP). Compound
      23, which is very potent, selective, efficacious in the diabetes PD model, and
      has an excellent pharmacokinetic profile, is selected as a clinical candidate. 

PMID- 23972442
TI  - Methadone toxicity: comparing tablet and syrup formulations during a decade in an
      academic poison center of Iran.
AB  - CONTEXT: Due to an increase in the number of methadone maintenance clinics in the
      past decade in Iran, acute methadone overdose has become one of the common
      poisonings in our society. OBJECTIVE: To compare the characteristics of methadone
      poisoning between syrup and tablet formulation as well as to discuss the relative
      advantages and disadvantages of poisoning from the perspective of toxicity.
      MATERIAL AND METHODS: In a retrospective cross-sectional study from 2000 to 2010,
      sampled data of all hospitalized methadone-overdosed patients were collected
      through chart review of hospital records. Concurrently, the total number of
      methadone sales was gathered. RESULTS: A total of 1426 patients with methadone
      poisoning had been hospitalized, including 1072 cases who consumed syrup or
      tablet solely. Mean +/- SD milligram ingested dose of syrup and tablet were 153
      +/- 339 and 88 +/- 274, respectively (p < 0.001). The mean time elapsed since
      ingestion was 9 +/- 9 and 7 +/- 7 h, respectively. Most of the accidental
      poisoning cases occurred as a result of syrup formulation, particularly by
      children under 12 years old after being mistaken for cough mixture or water.
      Conversely, exposure to methadone tablets was more common in patients with
      suicidal intent. There was no statistically significant difference between the
      rates of intubation and death between the two groups. DISCUSSION: Higher doses of
      methadone in the syrup form appear to exert a similar severity of poisoning and
      outcomes compared to lesser doses of that in the tablet form. Similarities in
      outcomes, despite differences in exposure history, may reflect relatively prompt
      transfer to hospital and adequate provision of clinical care, including
      supportive care and naloxone. CONCLUSION: In order to reduce the rate of
      poisoning, we recommend the use of child-resistant containers for dispensing
      syrup, reduction in methadone concentration, adding a coloring agent, special
      flavor, and education of patients on the safe storage of methadone in their home
      in order to reduce the occurrence of accidental poisonings.

PMID- 23972450
TI  - Evaluation of EGFR protein expression by immunohistochemistry using H-score and
      the magnification rule: re-analysis of the SATURN study.
AB  - INTRODUCTION: The phase III SATURN study demonstrated that first-line maintenance
      erlotinib extended progression-free survival (PFS) and overall survival (OS)
      versus placebo in patients with advanced non-small cell lung cancer (NSCLC).
      Analysis of epidermal growth factor receptor (EGFR) expression by
      immunohistochemistry (IHC) found no significant interaction between EGFR IHC
      status and PFS (p = 0.63) or OS (p = 0.52). The FLEX study of first-line
      cetuximab plus chemotherapy demonstrated that EGFR IHC expression was predictive
      of improved OS with cetuximab when assessed by H-score with a magnification rule.
      This novel method was used to reassess samples from SATURN. METHODS: The H-score
      method assigned a score of 0-300 to each patient, based on the percentage of
      cells stained at different intensities viewed at various magnifications. The
      discriminatory threshold was set at 200, per the FLEX study, and existing samples
      were re-read and classed as low (H-score < 200) or high (>=200) EGFR expression.
      PFS and OS were re-analyzed based on these new classifications. RESULTS: In the
      overall and EGFR wild-type populations, erlotinib provided a consistent survival
      benefit versus placebo. Hazard ratios (HRs) in the overall population were
      similar between EGFR IHC-positive and -negative patients for median PFS (HR 0.68
      [95% confidence interval (CI) 0.53-0.86] and 0.76 [95% CI 0.62-0.93],
      respectively) and OS (HR 0.80 [95% CI 0.62-1.05] and 0.80 [95% CI 0.64-1.01] for
      IHC-positive and IHC-negative, respectively). In the EGFR wild-type population,
      HRs were again similar between EGFR IHC-positive and -negative subpopulations for
      PFS (HR 0.69 [95% CI 0.51-0.95] and 0.84 [95% CI 0.63-1.12], respectively) and OS
      (HR 0.78 [95% CI 0.55-1.10] and 0.76 [95% CI 0.55-1.05], respectively).
      CONCLUSIONS: These data suggest that EGFR IHC does not have value as a marker to
      predict erlotinib benefit in the first-line maintenance setting for advanced
      NSCLC.

PMID- 23972451
TI  - Reverse flow in the middle cerebral artery in a severely intrauterine growth
      restricted fetus.

PMID- 23972452
TI  - Tension-free vaginal tape obturator versus Ajust adjustable single incision sling
      procedure in women with urodynamic stress urinary incontinence.
AB  - OBJECTIVE: To assess the efficacy and complications of inside-out transobturator
      tension-free vaginal tape (TVT-O) in comparison with a single incision sling
      procedure (Ajust) for the treatment of urodynamic stress urinary incontinence.
      STUDY DESIGN: Prospective closely matched controlled study. In total, 171
      patients were included in the study: 86 women underwent the TVT-O procedure,
      while in other 85 cases the Ajust procedure was performed. Subjective and
      objective cure, improvement and failure rates, mean operative time, hospital stay
      and incidence of complications were assessed. RESULTS: There was no statistically
      significant difference between the two groups for age, body mass index, parity,
      menopausal status and severity of prolapse. No major intraoperative complications
      occurred. There was no significant difference in the mean operative time and the
      duration of hospital stay between the two groups. The mean follow-up time of the
      study was 22.3 months (range 12-36 months). For the TVT-O group the objective
      cure rate was 86%, the improvement rate was 5.9% and the failure rate was 8.1%,
      while the subjective cure rate was 82.6%. For the Ajust group the objective cure
      rate was 84.7%, the improvement rate was 4.7%, 10.6% of patients showed no change
      in their symptoms and the subjective cure rate was 81.2%. CONCLUSIONS: The Ajust
      sling procedure presents success rates, at 22 months' mean follow up, comparable
      to the TVT-O method. Both techniques seem to be safe and effective for the
      treatment of urodynamic stress urinary incontinence.

PMID- 23972453
TI  - Strengths and limitations of a musculoskeletal model for an analysis of simulated
      meat cutting tasks.
AB  - This study assessed the capacity of a musculoskeletal model to predict the
      relative muscle activation changes as a function of the workbench height and the
      movement direction during a simulated meat cutting task. Seven subjects performed
      a cutting task alternating two cutting directions for 20 s at four different
      workbench heights. Kinematics, electromyography (EMG), and cutting force data
      were collected and used to drive a musculoskeletal model of the shoulder girdle.
      The model predicted the muscle forces exerted during the task. Both the recorded
      and computed activation of the muscles was then compared by means of cross
      correlation and by comparison of muscle activation trends with respect to the
      workstation parameters, i.e. cutting direction and workbench height. The results
      indicated that cutting movements involving arm flexion are preferable to movement
      requiring internal arm rotation and abduction. The optimal bench height for meat
      cutting tasks should be between 20 and 30 cm below the worker's elbow height. The
      present study underlines a beneficial use of musculoskeletal models for adjusting
      workstation parameters. 

PMID- 23972454
TI  - Neck and shoulder muscle activity during standardized work-related postural
      tasks.
AB  - The aim of the present study was to assess the activity levels of the
      sternocleidomastoid muscle and upper trapezius muscle during static postures
      under controlled and standardized conditions, and to determine whether the muscle
      activity differed between sexes. Electromyographic (EMG) activity was recorded
      unilaterally from the sternocleidomastoid and upper trapezius muscle in 17
      participants whilst they were performing various postural tasks. EMG amplitude
      was measured by the root mean square values of the raw signals and normalized to
      peak maximum contractile values for each muscle (%MVC). The intensity of muscle
      activity was ranked as light (<3%MVC), moderate (3%MVC <= EMG <= 8%MVC), and
      substantial (>8%MVC). During most tasks the two muscles contracted light to
      moderately. Head leaning and shoulder shrugging postures yielded substantial
      muscle activity in both muscles. Muscle activity did not differ significantly
      between male and female participants (F = 3.1; p = 0.078). Our findings provided
      normative values, which will enhance future studies of muscle activity during
      work in a natural, unrestrained environment. 

PMID- 23972455
TI  - Determination of selected perfluorinated alkyl acids and persistent organic
      pollutants from a small volume human serum sample relevant for epidemiological
      studies.
AB  - A simple and fast method is presented for the determination of selected
      persistent organic pollutants (POPs) and perfluorinated alkyl acids (PFAAs), a
      subgroup of per- and polyfluorinated alkyl substances (PFAS) from a single 200MUl
      aliquot of serum. Sample pretreatment starts with dispersive solid phase
      extraction of POPs to dichloromethane-hexane, which is immediately poured to
      cleanup column. POPs are eluted from column and concentrated for GC-MS/MS
      analysis. PFAAs are trapped to dispersant and are then extracted with ammonium
      acetate in methanol, concentrated and analysed with LC-MS/MS. For POPs, the limit
      of detection (LOD) ranged from 1.6 to 17pg/ml. Oxychlordane and
      dichlorodiphenyltrichloroethane had LODs in the upper end of this range as they
      were more labile and prone for interferences in the GC-MS/MS. For PFAAs, the LOD
      range from 0.027 to 0.068ng/ml. For POPs, the accuracy from Standard Reference
      Materials SRM 1589a and Arctic Monitoring and Assessment Programme (AMAP)
      intercalibration samples range from 74 to 127% and the repeatability (relative
      standard deviation, RSD%) from 2.0 to 15%. For PFAAs, the accuracy from AMAP
      samples ranged from 90 to 110% and from LOQ level spiked serum samples from 72 to
      133%. Repeatability from AMAP and LOQ samples ranged from 1.6 to 7.3% and 5.5 to
      15%, respectively. The presented method is useful in epidemiological studies
      where only limited amount of serum is available. 

PMID- 23972456
TI  - Ultrasound-assisted enzymatic hydrolysis for iodinated amino acid extraction from
      edible seaweed before reversed-phase high performance liquid chromatography
      inductively coupled plasma-mass spectrometry.
AB  - The combination of reverse phase high performance liquid chromatography (RP-HPLC)
      with inductively coupled plasma mass spectrometry (ICP-MS) was used for the
      determination of monoiodotyrosine (MIT) and diiodotyrosine (DIT) in edible
      seaweed. A sample pre-treatment based on ultrasound assisted enzymatic hydrolysis
      was optimized for the extraction of these iodinated amino acids. Pancreatin was
      selected as the most adequate type of enzyme, and parameters affecting the
      extraction efficiency (pH, temperature, mass of enzyme and extraction time) were
      evaluated by univariate approaches. In addition, extractable inorganic iodine
      (iodide) was also quantified by anion exchange high performance liquid
      chromatography (AE-HPLC) coupled with ICP-MS. The proposed procedure offered
      limits of detection of 1.1 and 4.3ngg(-1) for MIT and DIT, respectively. Total
      iodine contents in seaweed, as well as total iodine in enzymatic digests were
      measured by ICP-MS after microwave assisted alkaline digestion with
      tetramethylamonium hydroxide (TMAH) for total iodine assessment, and also by
      treating the pancreatin extracts (extractable total iodine assessment). The
      optimized procedure was successfully applied to five different types of edible
      seaweed. The highest total iodine content, and also the highest iodide levels,
      was found in the brown seaweed Kombu (6646+/-45MUgg(-1)). Regarding iodinated
      amino acids, Nori (a red seaweed) was by far the one with the highest amount of
      both species (42+/-3 and 0.41+/-0.024MUgg(-1) for MIT and DIT, respectively). In
      general, MIT concentrations were much higher than the amounts of DIT, which
      suggests that iodine from iodinated proteins in seaweed is most likely bound in
      the form of MIT residues. 

PMID- 23972457
TI  - Determination of the column hold-up volume in supercritical fluid chromatography
      using nitrous-oxide.
AB  - This study introduces a new tracer that is useful for the determination of the
      hold-up time or volume of packed columns, particularly of those used in
      supercritical fluid chromatography. The thermodynamic void volume of three
      columns packed with different adsorbents were determined using the weight
      difference method. These void volumes were used as the reference point in the
      further discussion. The hold-up volumes of these columns were determined under
      dynamic conditions, using nitrous oxide dissolved in methanol as the hold-up time
      marker. Changes in the hold-up volumes of these columns were monitored during
      changes of the volumetric flow rate of pure supercritical carbon dioxide and of
      dilute mixtures of organic modifier and supercritical carbon dioxide. The results
      suggest significant methanol enrichment on the adsorbent surface. 

PMID- 23972458
TI  - Capture chromatography for Mo-99 recovery from uranyl sulfate solutions: minimum
      column-volume design method.
AB  - Molybdenum-99 (Mo-99), generated from the fission of Uranium-235 (U-235), is the
      radioactive parent of the most widely used medical isotope, technetium-99m (Tc
      99m). An efficient, robust, low-pressure process is developed for recovering Mo
      99 from uranyl sulfate solutions. The minimum column volume and the maximum
      column length for required yield, pressure limit, and loading time are determined
      using a new graphical method. The method is based on dimensionless groups and
      intrinsic adsorption and diffusion parameters, which are estimated using a small
      number of experiments and simulations. The design is tested with bench-scale
      experiments with titania columns. The results show a high capture yield and a
      high stripping yield (95+/-5%). The design can be adapted to changes in design
      constraints or the variations in feed concentration, feed volume, or material
      properties. The graph shows clearly how the column utilization is affected by the
      required yield, loading time, and pressure limit. The cost effectiveness of
      various sorbent candidates can be evaluated based on the intrinsic parameters.
      This method can be used more generally for designing other capture chromatography
      processes. 

PMID- 23972459
TI  - Efficient tandem solid-phase extraction and liquid chromatography-triple
      quadrupole mass spectrometry method to determine polar benzotriazole,
      benzothiazole and benzenesulfonamide contaminants in environmental water samples.
AB  - An analytical method has been developed that allows the simultaneous
      determination of five benzotriazole (BTRs), four benzothiazole (BTs) and five
      benzenesulfonamide (BSAs) derivates. The method is based on tandem solid-phase
      extraction (SPE) with Oasis HLB followed by a clean-up step with Florisil. The
      chromatographic analysis was performed in less than 15min and detection was
      carried out with a triple quadrupole mass analyser operating in multiple reaction
      monitoring (MRM) mode. A comparison was performed between Oasis HLB and Oasis MAX
      sorbents for the solid-phase extraction, with Oasis HLB being the sorbent that
      gave the highest recoveries, ranging between 75% and 106%, depending on the
      compound and the matrix analysed. The proposed clean-up with Florisil sorbent
      reduced the matrix effect to below 20%. The repeatability (%RSD, 50-3000ng/L,
      n=3) of the method was less than 15% for all of the compounds in all of the
      matrices. The limits of detection (LODs) achieved ranged from 1ng/L for BTR in
      river water up to 100ng/L for BT in influent sewage. All of the compounds were
      determined in environmental waters such as river water and sewage. The highest
      concentrations determined corresponded to influent sewage samples in which the
      sum of concentrations for all compounds were between 4.6MUg/L and 8.0MUg/L. These
      concentrations were slightly reduced in secondary effluent and tertiary effluent
      sewage. Moreover, samples from tertiary effluent sewage based on ultra-filtration
      membrane treatments were also analysed and preliminary results seem to indicate
      that these treatments may be most effective for removing BTR, BT and BSA
      derivates. 

PMID- 23972460
TI  - Determination of cocaine in postmortem human liver exposed to overdose.
      Application of an innovative and efficient extraction/clean up procedure and gas
      chromatography-mass spectrometry analysis.
AB  - A simple and efficient method was developed for the determination of cocaine in
      post-mortem samples of human liver via solid-liquid extraction with low
      temperature partitioning (SLE-LTP) and analysis by gas chromatography coupled to
      mass spectrometry (GC-MS). The extraction procedure was optimized by evaluating
      the influence of the following variables: pH of the extract, volume and
      composition of the extractor solvent, addition of a sorbent material (PSA:
      primary-secondary amine) and NaCl to clean up and increase the ionic strength of
      the extract. A bovine liver sample that was free of cocaine was used as a blank
      for the optimization of the SLE-LTP extraction procedure. The highest recovery
      was obtained when crushed bovine liver (2g) was treated with 2mL of ultrapure
      water plus 8mL of acetonitrile at physiological pH (7.4). The results also
      indicated no need for using PSA and NaCl. The complete analytical procedure was
      validated for the following figures of merit: selectivity, lower limit of
      quantification (LLOQ), calibration curve, recovery, precision and accuracy (for
      within-run and between-run experiments), matrix effect, dilution integrity and
      stability. The within-run and between-run precision (at four levels) varied from
      2.1% to 9.4% and from 4.0% to 17.0%, respectively. A maximum deviation of 11.62%
      for the within-run and between-run accuracies in relation to the nominal
      concentrations was observed. Moreover, the LLOQ value for cocaine was 50.0ngg(-1)
      whereas no significant effects were noticed in the assays of dilution integrity
      and stability. To assess its overall performance, the optimized method was
      applied to the analysis of eight human liver samples collected from individuals
      who died due to the abusive consumption of cocaine. Due to the existence of a
      significant matrix effect, a blank human liver was used to construct a matrix
      matched analytical curve. The concentrations of cocaine found in these samples
      ranged from 333.5 to 5969ngg(-1). 

PMID- 23972461
TI  - Combined effects of mobile phase composition and temperature on the retention of
      phenolic antioxidants on an octylsilica polydentate column.
AB  - Combined effects of temperature and mobile-phase composition on retention and
      separation selectivity of phenolic acids and flavonoid compounds were studied in
      liquid chromatography on a polydentate Blaze C8 silica based column. The
      temperature effects on the retention can be described by van't Hoff equation.
      Good linearity of lnk versus 1/T graphs indicates that the retention is
      controlled by a single mechanism in the mobile phase and temperature range
      studied. Enthalpic and entropic contributions to the retention were calculated
      from the regression lines. Generally, enthalpic contributions control the
      retention at lower temperatures and in mobile phases with lower concentrations of
      methanol in water. Semi-empirical retention models describe the simultaneous
      effects of temperature and the volume fraction of the organic solvent in the
      mobile phase. Using the linear free energy-retention model, selective
      dipolarity/polarizability, hydrogen-bond donor, hydrogen-bond acceptor and
      molecular size contributions to retention were estimated at various mobile phase
      compositions and temperatures. In addition to mobile phase gradients, temperature
      programming can be used to reduce separation times. 

PMID- 23972462
TI  - On the effect of basic and acidic additives on the separation of the enantiomers
      of some basic drugs with polysaccharide-based chiral selectors and polar organic
      mobile phases.
AB  - This article reports the systematic study of the effect of basic and acidic
      additives on HPLC separation of enantiomers of some basic chiral drugs on
      polysaccharide-based chiral columns under polar organic mobile-phase conditions.
      In contrary to generally accepted opinion that the basic additives improve the
      separation of enantiomers of basic compounds, the multiple scenarios were
      observed including the increase, decrease, disappearance and appearance of
      separation, as well as the reversal of the enantiomer elution order of studied
      basic compounds induced by the acidic additives. These effects were observed on
      most of the studied 6 chiral columns in 2-propanol and acetonitrile as mobile
      phases and diethylamine as a basic additive. As acidic additives formic acid was
      used systematically and acetic acid and trifluoroacetic acid were applied for
      comparative purposes. This study illustrates that the minor acidic additives to
      the mobile phase can be used as for the adjustment of separation selectivity and
      the enantiomer elution order of basic compounds, as well as for study of chiral
      recognition mechanisms with polysaccharide-based chiral stationary phases. 

PMID- 23972463
TI  - Carboxylated multiwalled carbon nanotubes/polydimethylsiloxane, a new coating for
      96-blade solid-phase microextraction for determination of phenolic compounds in
      water.
AB  - A new thin-film, carboxylated multiwalled carbon nanotubes/polydimethylsiloxane
      (MWCNTs-COOH/PDMS) coating was developed for 96-blade solid-phase microextraction
      (SPME) system followed by high performance liquid chromatography with ultraviolet
      detection (HPLC-UV). The method provided good extraction efficiency (64-90%) for
      three spiked levels, with relative standard deviations (RSD)<=6%, and detection
      limits between 1 and 2 MUg/L for three phenolic compounds. The MWCNTs-COOH/PDMS
      96-blade SPME system presents advantages over traditional methods due to its
      simplicity of use, easy coating preparation, low cost and high sample throughput
      (2.1 min per sample). The developed coating is reusable for a minimum of 110
      extractions with good extraction efficiency. The coating provided higher
      extraction efficiency (3-8 times greater) than pure PDMS coatings.

PMID- 23972464
TI  - Effects of the back pressure and the temperature on the finite layer thickness of
      the adsorbed phase layer in supercritical fluid chromatography.
AB  - The excess adsorption isotherm of ethanol from liquid carbon dioxide on a
      silicagel column was determined in a range of back pressures and temperatures.
      The retention patterns of minor disturbance peaks were mapped and their
      dependences on the applied back pressure and column temperature measured. The
      analysis of the linear decreasing part of the excess isotherm around its
      inflection point provided the finite layer thickness of the adsorbed phase. Our
      results show that increasing the temperature and decreasing the back pressure
      result in a thicker layer of the layer of enriched organic solvent above the
      silicagel surface. 

PMID- 23972465
TI  - Neutral, charged and stratified polar monoliths for hydrophilic interaction
      capillary electrochromatography.
AB  - Novel polar monoliths were introduced for hydrophilic interaction capillary
      electrochromatography (HI-CEC). In one case, a neutral polar monolith resulted
      from the in situ polymerization of glyceryl methacrylate (GMM) and
      pentaerythritol triacrylate (PETA) in a ternary porogenic solvent. GMM and PETA
      possess hydroxyl functional groups, which impart the monolith with hydrophilic
      interaction sites. This monolith is designated as hydroxy monolith. Although the
      hydroxy monolith is neutral and void of fixed charges on the surface, a
      relatively strong cathodal EOF was observed due to the electric double layer
      formed by the adsorption of ions from the mobile phase, producing a bulk mobile
      phase flow. The second monolith is charged and referred to as AP-monolith that
      possesses amine/amide functionalities on its surface, and was prepared by the in
      situ polymerization of N-(3-aminopropyl) methacrylamide hydrochloride (NAPM) and
      ethylene dimethacrylate (EDMA) in the presence of cyclohexanol, dodecanol and
      methanol as porogens. Over the pH range studied a strong anodal EOF was observed.
      The AP-monolith was further exploited in HI-CEC by modifying its surface with
      neutral mono- and oligosaccharides to produce a series of the so called sugar
      modified AP-monoliths (SMAP-monolith), which are considered as stratified
      hydrophilic monoliths possessing a sub-layer of polar amine/amide groups and a
      top layer of sugar (a polyhydroxy top layer). The SMAP-monoliths can be viewed as
      a blend of both the hydroxy monolith and the AP-monolith. The polarity of the
      various monoliths seems to follow the order: hydroxy monolith<AP-monolith<SMAP
      monolith. The novel monoliths were characterized over a wide range of elution
      conditions with a variety of polar solutes including phenols, substituted
      phenols, nucleic acid bases, nucleosides and nucleotides. 

PMID- 23972466
TI  - Association between the adiponectin +45T>G genotype and risk of cardiovascular
      disease: a meta-analysis.
AB  - BACKGROUND: Numerous studies have investigated the association between
      adiponectin +45 nucleotide T/G (+45T>G) polymorphisms and cardiovascular disease
      (CVD). However, these studies have been inconclusive because of obvious
      inconsistencies among results. The present study aims to quantify the strength of
      the association between +45T>G (rs2241766) in the adiponectin gene and the risk
      of CVD. METHODS: We searched the PubMed, Embase, and Wangfang databases for
      studies related to the association between the adiponectin +45T>G genotype and
      the risk of CVD. We estimated the summary odds ratio (OR) with 95% confidence
      interval (CI) to assess the association. RESULTS: A total of 28 case-control
      studies, with 12,378 CVD cases and 19,368 controls, were included in the meta
      analysis. The meta-analysis of the 28 studies showed that the single-nucleotide
      polymorphism (SNP) +45T>G genotype was associated with an increased risk of CVD
      (random-effects OR = 1.22, 95% CI 1.08-1.39, p = 0.002). After adjusting for
      heterogeneity, the meta-analysis showed that the SNP +45T>G genotype was
      associated with the risk of CVD in the analyses of the total population and the
      Caucasian population (for the total population, fixed-effects OR = 1.11, 95% CI
      1.01-1.23, p = 0.012; for the Caucasian population, fixed-effects OR = 1.16, 95%
      CI 1.01-1.34, p = 0.039). No significant association was found in other
      populations. Evidence of publication bias was observed in the meta-analysis.
      CONCLUSION: A significant association between rs2241766 in the adiponectin gene
      and CVD was established by the meta-analysis.

PMID- 23972467
TI  - Cancer: a missing link in ecosystem functioning?
AB  - Cancer is a disease that affects the majority of metazoan species and, before
      directly causing host death, is likely to influence the competitive abilities of
      individuals, their susceptibility to pathogens, their vulnerability to predators,
      and their ability to disperse. Despite the potential importance of these
      ecological impacts, cancer is rarely incorporated into model ecosystems. We
      describe here the diversity of ways in which oncogenic phenomena, from
      precancerous lesions to generalized metastatic cancers, may affect ecological
      processes that govern biotic interactions. We argue that oncogenic phenomena,
      despite their complexity, can have significant and sometimes predictable
      ecological consequences. Our aim is to provide a new perspective on the
      ecological and evolutionary significance of cancer in wildlife, and to stimulate
      research on this topic. 

PMID- 23972468
TI  - [Alpha/beta ratio revisited in the era of hypofractionation].
AB  - Large doses per fraction are not recommended in daily radiotherapy due to a
      higher risk of late normal tissue injury. The technical refinements of modern
      radiotherapy and suggestions that some tumors could be sensitive to dose per
      fraction have renewed the interest in hypofractionated schedules. The estimation
      of alpha/beta ratio value requires large samples of carefully evaluated patients
      in whom total and fractional doses have varied independently. Tumor repopulation
      has to be considered when the treatment duration is altered. Without setting
      aside conflicting publication, the alpha/beta ratio values for prostate and
      breast (after lumpectomy) cancers could be as low as 2.5 Gy and 4 Gy,
      respectively. While it is too early to change our routine protocols, the time has
      come to conduct clinical trials comparing different fractionation schedules.

PMID- 23972469
TI  - [Radiotherapy for cervix carcinomas: clinical target volume delineation].
AB  - Concurrent chemoradiation followed by brachytherapy is currently the standard
      treatment for locally advanced cervix carcinomas. Modern radiation techniques
      require planning based on 3D images, and therefore an accurate delineation of
      target volumes. The clinical target volume (CTV) used for the different phases of
      treatment are now well defined, but are not always easy to delineate on a CT scan
      which is currently the standard examination for simulation in radiotherapy. MRI
      and PET-CT are routinely performed at diagnosis, and can be used to improve the
      accuracy of the delineation. The objective of this review is to describe the
      definitions and recommendations of CTV in the treatment of cervical cancer. 

PMID- 23972470
TI  - Structural basis for autoactivation of human Mst2 kinase and its regulation by
      RASSF5.
AB  - The tumor-suppressive Hippo pathway controls tissue homeostasis through balancing
      cell proliferation and apoptosis. Activation of the kinases Mst1 and Mst2
      (Mst1/2) is a key upstream event in this pathway and remains poorly understood.
      Mst1/2 and their critical regulators RASSFs contain Salvador/RASSF1A/Hippo
      (SARAH) domains that can homo- and heterodimerize. Here, we report the crystal
      structures of human Mst2 alone and bound to RASSF5. Mst2 undergoes activation
      through transautophosphorylation at its activation loop, which requires SARAH
      mediated homodimerization. RASSF5 disrupts Mst2 homodimer and blocks Mst2
      autoactivation. Binding of RASSF5 to already activated Mst2, however, does not
      inhibit its kinase activity. Thus, RASSF5 can act as an inhibitor or a potential
      positive regulator of Mst2, depending on whether it binds to Mst2 before or after
      activation-loop phosphorylation. We propose that these temporally sensitive
      functions of RASSFs enable the Hippo pathway to respond to and integrate diverse
      cellular signals.

PMID- 23972471
TI  - Conformational analysis of NMDA receptor GluN1, GluN2, and GluN3 ligand-binding
      domains reveals subtype-specific characteristics.
AB  - The NMDA receptor family of glutamate receptor ion channels is formed by obligate
      heteromeric assemblies of GluN1, GluN2, and GluN3 subunits. GluN1 and GluN3 bind
      glycine, whereas GluN2 binds glutamate. Crystal structures of the GluN1 and
      GluN3A ligand-binding domains (LBDs) in their apo states unexpectedly reveal open
      and closed-cleft conformations, respectively, with water molecules filling the
      binding pockets. Computed conformational free energy landscapes for GluN1,
      GluN2A, and GluN3A LBDs reveal that the apo-state LBDs sample closed-cleft
      conformations, suggesting that their agonists bind via a conformational selection
      mechanism. By contrast, free energy landscapes for the AMPA receptor GluA2 LBD
      suggest binding of glutamate via an induced-fit mechanism. Principal component
      analysis reveals a rich spectrum of hinge bending, rocking, twisting, and
      sweeping motions that are different for the GluN1, GluN2A, GluN3A, and GluA2
      LBDs. This variation highlights the structural complexity of signaling by
      glutamate receptor ion channels.

PMID- 23972472
TI  - Transient domain interactions enhance the affinity of the mitotic regulator Pin1
      toward phosphorylated peptide ligands.
AB  - The mitotic regulator Pin1 plays an important role in protein quality control and
      age-related medical conditions such as Alzheimer disease and Parkinson disease.
      Although its cellular role has been thoroughly investigated during the past
      decade, the molecular mechanisms underlying its function remain elusive. We
      provide evidence for interactions between the two domains of Pin1. Several
      residues displayed unequivocal peak splits in nuclear magnetic resonance spectra,
      indicative of two different conformational states in equilibrium. Pareto analysis
      of paramagnetic relaxation enhancement data demonstrates that the two domains
      approach each other upon addition of a nonpeptidic ligand. Titration experiments
      with phosphorylated peptides monitored by fluorescence anisotropy and chemical
      shift perturbation indicate that domain interactions increase Pin1's affinity
      toward peptide ligands. We propose this interplay of the domains and ligands to
      be a general mechanism for a large class of two-domain proteins.

PMID- 23972473
TI  - Structural mimicry of a-loop tyrosine phosphorylation by a pathogenic FGF
      receptor 3 mutation.
AB  - The K650E gain-of-function mutation in the tyrosine kinase domain of FGF receptor
      3 (FGFR3) causes Thanatophoric Dysplasia type II, a neonatal lethal congenital
      dwarfism syndrome, and when acquired somatically, it contributes to
      carcinogenesis. In this report, we determine the crystal structure of the FGFR3
      kinase domain harboring this pathogenic mutation and show that the mutation
      introduces a network of intramolecular hydrogen bonds to stabilize the active
      state conformation. In the crystal, the mutant FGFR3 kinases are caught in the
      act of trans-phosphorylation on a kinase insert autophosphorylation site,
      emphasizing the fact that the K650E mutation circumvents the requirement for A
      loop tyrosine phosphorylation in kinase activation. Analysis of this trans
      phosphorylation complex sheds light onto the determinants of tyrosine trans
      phosphorylation specificity. We propose that the targeted inhibition of this
      pathogenic FGFR3 kinase may be achievable by small molecule kinase inhibitors
      that selectively bind the active-state conformation of FGFR3 kinase.

PMID- 23972474
TI  - Supportive and palliative care for metastatic breast cancer: resource allocations
      in low- and middle-income countries. A Breast Health Global Initiative 2013
      consensus statement.
AB  - Many women diagnosed with breast cancer in low- and middle-income countries
      (LMICs) present with advanced-stage disease. While cure is not a realistic
      outcome, site-specific interventions, supportive care, and palliative care can
      achieve meaningful outcomes and improve quality of life. As part of the 5th
      Breast Health Global Initiative (BHGI) Global Summit, an expert international
      panel identified thirteen key resource recommendations for supportive and
      palliative care for metastatic breast cancer. The recommendations are presented
      in three resource-stratified tables: health system resource allocations, resource
      allocations for organ-based metastatic breast cancer, and resource allocations
      for palliative care. These tables illustrate how health systems can provide
      supportive and palliative care services for patients at a basic level of
      available resources, and incrementally add services as more resources become
      available. The health systems table includes health professional education,
      patient and family education, palliative care models, and diagnostic testing. The
      metastatic disease management table provides recommendations for supportive care
      for bone, brain, liver, lung, and skin metastases as well as bowel obstruction.
      The third table includes the palliative care recommendations: pain management,
      and psychosocial and spiritual aspects of care. The panel considered pain
      management a priority at a basic level of resource allocation and emphasized the
      need for morphine to be easily available in LMICs. Regular pain assessments and
      the proper use of pharmacologic and non-pharmacologic interventions are
      recommended. Basic-level resources for psychosocial and spiritual aspects of care
      include health professional and patient and family education, as well as patient
      support, including community-based peer support. 

PMID- 23972475
TI  - Breast cancer in women at high risk: the role of rapid genetic testing for BRCA1
      and -2 mutations and the consequences for treatment strategies.
AB  - Specific clinical questions rise when patients, who are diagnosed with breast
      cancer, are at risk of carrying a mutation in BRCA1 and -2 gene due to a strong
      family history or young age at diagnosis. These questions concern topics such as
      1. Timing of genetic counseling and testing, 2. Choices to be made for BRCA1 or 
      2 mutation carriers in local treatment, contralateral treatment, (neo)adjuvant
      systemic therapy, and 3. The psychological effects of rapid testing. The
      knowledge of the genetic status might have several advantages for the patient in
      treatment planning, such as the choice whether or not to undergo mastectomy
      and/or prophylactic contralateral mastectomy. The increased risk of developing a
      second breast cancer in the ipsilateral breast in mutation carriers, is only
      slightly higher after primary cancer treatment, than in the general population.
      Prophylactic contralateral mastectomy provides a substantial reduction of
      contralateral breast cancer, although only a small breast cancer specific
      survival benefit. Patients should be enrolled in clinical trials to investigate
      (neo)-adjuvant drug regimens, that based on preclinical and early clinical
      evidence might be targeting the homologous recombination defect, such as platinum
      compounds and PARP inhibitors. If rapid testing is performed, the patient can
      make a well-balanced decision. Although rapid genetic counseling and testing
      might cause some distress, most women reported this approach to be worthwhile. In
      this review the literature regarding these topics is evaluated. Answers and
      suggestions, useful in clinical practice are discussed. 

PMID- 23972476
TI  - Improved anticoagulation of titanium by sequential immobilization of
      oligo(ethylene glycol) and 2-methacryloyloxyethyl phosphorylcholine.
AB  - Titanium and its alloys have been widely used for blood-contacting biomedical
      devices; however, their blood compatibility needs to be improved. In this study,
      titanium surface was modified by sequential immobilization of oligo(ethylene
      glycol) (OEG) and 2-methacryloyloxyethyl phosphorylcholine (MPC) to improve its
      anticoagulation. Water contact angle results showed an excellent hydrophilic
      surface after the immobilization. Attenuated total reflectance-Fourier transform
      infrared spectroscopy (ATR-FTIR) confirmed that OEG and MPC were successfully
      immobilized on titanium surface. Static platelet adhesion and APTT (activated
      partial thromboplastin time) experiments suggested that the anticoagulation of
      titanium was significantly enhanced by the immobilization of OEG and further by
      subsequent MPC grafting. The approach in the present study opens up a window of
      promising an effective and efficient method to improve the anticoagulation of
      blood-contact biomedical devices such as coronary stents. 

PMID- 23972478
TI  - A device for the rapid transfer/transplantation of living cell sheets with the
      absence of cell damage.
AB  - In this study, we developed a device that could easily, rapidly, and completely
      transfer cell sheets from one material to another or transplant cell sheets onto
      the dorsal subcutaneous tissues of rats without leaving residual cells. Because
      the manipulation is as simple as pipetting, technical expertise is not required
      to transfer cell sheets very rapidly (the transfer time was 3.7 +/- 1.6 s) using
      the device compared with that of a conventional method using a pipette (430 +/-
      180 s). After transfer by the device, C2C12 skeletal myoblast sheets showed
      active cell metabolism, cell viability, and very high production of vascular
      endothelial growth factor and stromal-derived factor-1alpha, indicating transfer
      without cell damage. Cardiac cell sheets after transfer showed spontaneous and
      synchronous beating, indicating intact cell-cell junctions and ion channel
      proteins on the cell surface. In addition, the device allowed us to transfer
      C2C12 cell sheets onto soft, rugged and curved surfaces such as human hands.
      Furthermore, cardiac cell sheets adhered rapidly and tightly onto the dorsal
      subcutaneous tissues of rats. This transfer/transplantation device may be a
      powerful tool in cell sheet-based tissue engineering and regenerative medicine.

PMID- 23972477
TI  - Enhancing microvascular formation and vessel maturation through temporal control
      over multiple pro-angiogenic and pro-maturation factors.
AB  - Therapeutic stimulation of angiogenesis to re-establish blood flow in ischemic
      tissues offers great promise as a treatment for patients suffering from
      cardiovascular disease or trauma. Since angiogenesis is a complex, multi-step
      process, different signals may need to be delivered at appropriate times in order
      to promote a robust and mature vasculature. The effects of temporally regulated
      presentation of pro-angiogenic and pro-maturation factors were investigated in
      vitro and in vivo in this study. Pro-angiogenic factors vascular endothelial
      growth factor (VEGF) and angiopoietin 2 (Ang2) cooperatively promoted endothelial
      sprouting and pericyte detachment in a three-dimensional in vitro EC-pericyte co
      culture model. Pro-maturation factors platelet-derived growth factor B (PDGF) and
      angiopoietin 1 (Ang1) inhibited the early stages of VEGF- and Ang2-mediated
      angiogenesis if present simultaneously with VEGF and Ang2, but promoted these
      behaviors if added subsequently to the pro-angiogenesis factors. VEGF and Ang2
      were also found to additively enhance microvessel density in a subcutaneous model
      of blood vessel formation, while simultaneously administered PDGF/Ang1 inhibited
      microvessel formation. However, a temporally controlled scaffold that released
      PDGF and Ang1 at a delay relative to VEGF/Ang2 promoted both vessel maturation
      and vascular remodeling without inhibiting sprouting angiogenesis. Our results
      demonstrate the importance of temporal control over signaling in promoting
      vascular growth, vessel maturation and vascular remodeling. Delivering multiple
      growth factors in combination and sequence could aid in creating tissue
      engineered constructs and therapies aimed at promoting healing after acute wounds
      and in chronic conditions such as diabetic ulcers and peripheral artery disease.

PMID- 23972479
TI  - Pelvic circumferential compression devices benefit patients with pelvic fractures
      who need transfers.
AB  - INTRODUCTION: Patients with pelvic fracture usually require transfers to trauma
      centers for additional advanced treatment. Patient safety during the transfer
      should always be a priority. The noninvasive pelvic circumferential compression
      device (PCCD) can reportedly provide a tamponade effect, which reduces
      hemorrhage. In the present study, we evaluated the feasibility and efficiency of
      PCCD in patients with pelvic fracture who required transfer to trauma centers.
      MATERIALS AND METHODS: In the present study, we aimed to evaluate patients with
      pelvic fractures who were transferred from other hospitals. We investigated and
      compared the characteristics of these types of patients with and without
      pretransfer PCCD. We compared 2 groups (with and without pretransfer PCCD) of
      patients under different situations (unstable pelvic fracture, stable pelvic
      fracture, or indicated for transcatheter arterial embolization). We also analyzed
      the characteristics of patients with unstable pelvic fracture who were initially
      evaluated as having stable pelvic fracture primarily before being transferred.
      RESULTS: During the 53-month period, we enrolled 585 patients in the study. The
      patients with unstable pelvic fractures who received pretransfer PCCDs required
      significantly fewer blood transfusions (398.4 +/- 417.6 mL vs 1954.5 +/- 249.0
      mL, P < .001), shorter intensive care unit length of stay (LOS; 6.6 +/- 5.2 days
      vs 11.8 +/- 7.7 days, P = .024), and shorter hospital LOS (9.4 +/- 7.0 days vs
      19.5 +/- 13.7 days, P = .006) compared with patients who did not receive the
      pretransfer PCCD. The stable patients who received pretransfer PCCDs required
      significantly fewer blood transfusions (120.2 +/- 178.5 mL vs 231.8 +/- 206.2 mL,
      P = .018) and had shorter intensive care unit LOS (1.7 +/- 3.3 days vs 3.4 +/-
      2.9 days, P = .029) and shorter hospital LOS (6.8 +/- 5.1 days vs 10.4 +/- 7.6
      days, P = .018) compared with patients who did not receive the pretransfer PCCD.
      CONCLUSION: Pelvic circumferential compression devices benefit patients with
      pelvic fracture who need to be transferred to trauma centers. Pretransfer PCCDs
      appeared to be a feasible and safe procedure during the transfer. In discussions
      between the referring physicians and the receiving physicians, we recommend using
      pretransfer PCCDs.

PMID- 23972480
TI  - "Sick" or "not-sick": accuracy of System 1 diagnostic reasoning for the
      prediction of disposition and acuity in patients presenting to an academic ED.
AB  - OBJECTIVE: System 1 decision-making is fast, resource economic, and intuitive
      (eg, "your gut feeling") and System 2 is slow, resource intensive, and analytic
      (eg, "hypothetico-deductive"). We evaluated the performance of disposition and
      acuity prediction by emergency physicians (EPs) using a System 1 decision-making
      process. METHODS: We conducted a prospective observational study of attending EPs
      and emergency medicine residents. Physicians were provided patient demographics,
      chief complaint, and vital sign data and made two assessments on initial
      presentation: (1) likely disposition (discharge vs admission) and (2) "sick" vs
      "not-sick". A patient was adjudicated as sick if he/she had a disease process
      that was potentially life or limb threatening based on pre-defined operational,
      financial, or educationally derived criteria. RESULTS: We obtained 266
      observations in 178 different patients. Physicians predicted patient disposition
      with the following performance: sensitivity 87.7% (95% CI 81.4-92.1), specificity
      65.0% (95% CI 56.1-72.9), LR+ 2.51 (95% CI 1.95-3.22), LR- 0.19 (95% CI 0.12
      0.30). For the sick vs not-sick assessment, providers had the following
      performance: sensitivity 66.2% (95% CI 55.1-75.8), specificity 88.4% (95% CI 83.0
      92.2), LR+ 5.69 (95% CI 3.72-8.69), LR- 0.38 (95% CI 0.28-0.53). CONCLUSION: EPs
      are able to accurately predict the disposition of ED patients using system 1
      diagnostic reasoning based on minimal available information. However, the
      prognostic accuracy of acuity prediction was limited.

PMID- 23972483
TI  - Pulsed high-intensity focused ultrasound enhances apoptosis of pancreatic cancer
      xenograft with gemcitabine.
AB  - We sought to investigate whether concurrent exposure to pulsed high-intensity
      focused ultrasound (HIFU) and the chemotherapeutic drug gemcitabine would enhance
      apoptosis in pancreatic cancer. A pancreatic cancer xenograft model was
      established using BALB/c nude mice and human pancreatic cancer cells (PANC-1). In
      the first study, mice were randomly allocated into one of four groups: control (n
      = 4), HIFU alone (n = 4), gemcitabine (GEM) alone (n = 28) and concurrent
      treatment with HIFU and gemcitabine (HIGEM) (n = 28). The GEM and HIGEM groups
      were subdivided into four subgroups (16 mice) according to the drug dose injected
      (50-200 mg/kg) and another four subgroups (16 mice) according to the time
      interval between drug injection and HIFU treatment (each subgroup, n = 4).
      Apoptosis rates were evaluated using the TUNEL (terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling) assay and percentage of necrosis, as
      evaluated with Harris' hematoxylin solution and eosin Y stain, 3 d after
      treatment. The second study was performed to evaluate tumor growth rates of the
      four groups. Each group was treated weekly for 3 wk, and tumor size was
      periodically measured for up to 4 wk from the beginning of treatment. In the
      first study, overall rates of apoptosis were significantly higher in the HIGEM
      group than in the GEM group (p = 0.02). In a subgroup analysis, HIGEM was
      superior to GEM in enhancing apoptosis at gemcitabine dosages of 150-200 mg/kg
      gemcitabine and intervals between gemcitabine and HIFU less than 2 h (p = 0.01).
      In the second study, HIGEM treatment resulted in the slowest tumor growth.
      However, despite a visible distinction, none of the differences found between the
      HIGEM and GEM groups were statistically significant (p > 0.05). Treatment with
      both HIFU and gemcitabine might enhance cell apoptosis and reduce tumor growth in
      pancreatic carcinoma. For this concurrent treatment, a high dosage of gemcitabine
      and a short-term delay before HIFU are recommended to maximize the therapeutic
      effect. 

PMID- 23972484
TI  - Correlation between classical rheometry and supersonic shear wave imaging in
      blood clots.
AB  - The assessment of coagulating blood elasticity has gained importance as a result
      of several studies that have correlated it to cardiovascular pathologic
      conditions. In this study we use supersonic shear wave imaging (SSI) to measure
      viscoelastic properties of blood clots. At the same time, classical rheometry
      experiments were carried out on the same blood samples taken within the first few
      seconds of coagulation. Using SSI, phase velocities of the shear wave indicated
      increasing dispersion with time. In all cases, the frequency bandwidth of
      propagating shear waves changed from 20-50 Hz at the first few min of coagulation
      to around 300 Hz toward the end of experiments. Using the values of G' and G"
      from the rheometry studies, the theoretical shear wave velocities were calculated
      and correlated with SSI measurements. Results of the two techniques were in very
      good agreement, confirming that SSI provides accurate measurements of
      viscoelastic properties as corroborated by conventional rheometric measurements. 

PMID- 23972485
TI  - Elasticity estimates from images of crawling waves generated by miniature surface
      sources.
AB  - We describe a surface-based approach to the generation of shear wave interference
      patterns, called crawling waves (CrW), within a medium and derive local estimates
      of biomechanical properties of tissue. In previous experiments, elongated bars
      operating as vibration sources were used to generate CrW propagation in samples.
      In the present study, however, a pair of miniature circular vibration sources was
      applied to the overlying skin to generate the CrW within the medium. The shape
      and position of the miniature sources make this configuration more applicable for
      in vivo implementation. A modified ultrasound imaging system is used to display
      the CrW propagation. A shear speed mapping algorithm is developed using a
      detailed analysis of the CrW. The proposed setup is applied to several
      biomaterials including a homogeneous phantom, an inhomogeneous phantom and an ex
      vivo human liver. The data are analyzed using the mapping algorithm to reveal the
      biomechanical properties of the biomaterials.

PMID- 23972486
TI  - Combined photoacoustic and acoustic imaging of human breast specimens in the
      mammographic geometry.
AB  - A photoacoustic volume imaging (PAVI) system was designed to study breast cancer
      detection and diagnosis in the mammographic geometry in combination with
      automated 3-D ultrasound (AUS). The goal of the work described here was to
      validate the design and evaluate its performance in human breast tissues for non
      invasive imaging of deeply positioned structures covering such geometry. The good
      penetration of near-infrared light and high receiving sensitivity of a broad
      bandwidth, 572-element, 2-D polyvinylidene fluoride (PVDF) array at a low center
      frequency of 1 MHz were used with 20 channel simultaneous acquisition. Pseudo
      lesions filled with dilute blood were imaged in three human breast specimens at
      various depths up to 49 mm. With near-infrared light illumination and 256-sample
      averaging, the extrapolated maximum depth in imaging a 2.4-mm blood-rich lesion
      with a 3-dB contrast-to-noise ratio in a compressed breast was 54 mm. Three
      dimensional photoacoustic volume image stacks of the breasts were co-registered
      with 3-D ultrasound image stacks, suggesting for the first time that PAVI, based
      on the intrinsic tissue contrast, can visualize tissue interfaces other than
      those with blood, including the inner skin surface and connective tissue sheets.
      With the designed system, PAVI revealed satisfactory imaging depth and
      sensitivity for coverage of the entire breast when imaged from both sides in the
      mammographic geometry with mild compression. 

PMID- 23972487
TI  - Comparing the diagnostic value of ultrasound and magnetic resonance imaging for
      placenta accreta: a systematic review and meta-analysis.
AB  - The aim of this study was to evaluate the diagnostic value of ultrasound (US) as
      compared with magnetic resonance imaging (MRI) in the detection of placenta
      accreta. Sensitivity, specificity, summary receiver operating characteristic
      curves and areas under the curve (AUCs) were described and calculated using Meta
      Disc Statistical Software, Version 1.4 (Unit of Clinical Biostatistics, Ramon y
      Cajal Hospital, Madrid, Spain). In the 13 studies included, US sensitivity was
      83% (95% confidence interval [CI] 77%-88%), US specificity was 95% (95% CI: 93%
      96%) and the diagnostic odds ratio (DOR) was 63.41 (95% CI: 29.04-138.48). In the
      MRI studies, sensitivity was 82% (95% CI: 72%-90%), specificity was 88% (95% CI:
      81%-94%) and the DOR was 22.95 (95% CI: 3.19-165.11). Summary receiver operating
      characteristic analysis indicated that the diagnostic value of US in detection of
      placenta accreta is not significantly different from that of MRI. Both US and MRI
      were highly sensitive and specific in the detection of placenta accreta to
      support effective diagnostic methods. 

PMID- 23972488
TI  - In vitro localized release of thermosensitive liposomes with ultrasound-induced
      hyperthermia.
AB  - Localized drug delivery with ultrasound-induced hyperthermia can enhance the
      therapeutic index of chemotherapeutic drugs by improving efficacy and reducing
      systemic toxicity. A novel in vitro method for the activation of drug-loaded
      thermosensitive liposomes is described. In particular, a dual-compartment,
      acoustically transparent container is used in which thermosensitive liposomes
      suspended in cell culture medium are immersed in a thermally absorptive medium,
      glycerol. Hyperthermia is induced with ultrasound in the glycerol, which in turn
      heats the culture medium by thermal conduction. The method approximately mimics
      the in vivo scenario of thermosensitive liposomes collected in the interstitial
      spaces of tumors, where ultrasound induces hyperthermia in the tumor tissue,
      which in turn heats the thermosensitive liposomes by conduction and induces
      release of the encapsulated drug. The acoustic conditions for the desired
      hyperthermia are derived theoretically and validated experimentally. Eighty
      percent release of doxorubicin from thermosensitive liposomes is achieved. 

PMID- 23972489
TI  - Left ventricular function and functional recovery early and late after myocardial
      infarction: a prospective pilot study comparing two-dimensional strain,
      conventional echocardiography, and radionuclide myocardial perfusion imaging.
AB  - BACKGROUND: Visual left ventricular (LV) wall motion scoring is well established
      for the assessment of LV function, yet it is subjective, circumstantial, and
      relative and requires long training. Quantification of myocardial shortening
      (strain) using two-dimensional speckle-tracking is potentially less subjective.
      In this study, quantifiable LV contraction (two-dimensional strain) was
      prospectively cross-related with wall motion score (WMS) and radionuclide
      myocardial perfusion imaging (MPI) score in 20 patients (mean age, 54 +/- 9
      years) with acute myocardial infarctions, early and late after percutaneous
      revascularization. METHODS: Echocardiography and rest MPI were performed 3 to 5
      days after acute myocardial infarction. Echocardiography was repeated at 4
      months. Peak segmental and global endocardial longitudinal strain (LS) and
      circumferential strain (CS) were measured, and principal strain was calculated.
      Volumes, WMS, MPI scores, and strain were assessed independently. RESULTS: Two
      dimensional strain, visual WMS, and radionuclide MPI score correlated closely.
      Strain thresholds for abnormal WMS were 11.7% for early LS, 18.2% for early CS,
      13.9% for late LS, and 19.1% for late CS. Late principal strain correlated better
      with WMS and MPI score than either LS or CS. CS varied minimally over time, while
      LS improved in most segments. Higher early CS (>15%) was predictive of segmental
      functional recovery. MPI score correlated better with late rather than early
      strain, probably because early resting perfusion defects represent permanent
      damage. CONCLUSIONS: In this pilot study, strain correlated with
      echocardiographic WMS and the extent of ischemia (MPI score) early and late after
      revascularization in patients with acute myocardial infarction. Longitudinal and
      circumferential strain uncoupling was observed. LS appeared to be more sensitive
      to acute ischemia, whereas CS correlated better with improvement after
      revascularization.

PMID- 23972490
TI  - Specific left ventricular twist-untwist mechanics during exercise in children.
AB  - BACKGROUND: In adults, left ventricular (LV) systolic twist is an important
      factor that determines LV filling, both at rest and during exercise. In children,
      lower LV twist has been demonstrated at rest, but its adaptation during exercise
      and its functional consequences on LV filling are unknown. METHODS: Using speckle
      tracking echocardiography, LV twist-untwist mechanics were studied in 25 children
      (aged 10-12 years) and 20 young adults (aged 18-44 years) at rest and during
      three exercise workloads performed at 20%, 30%, and 40% of their maximal aerobic
      power. RESULTS: At rest, LV twist was lower in children, because of a higher
      temporal dispersion of peak rotation between base and apex. During exercise, the
      increase of basal rotation was blunted in children compared with adults (-6.7 +/-
      2.7 degrees  vs -9.0 +/- 2.0 degrees  at 40% of maximal aerobic power, P < .05).
      Consequently, LV twist increased to a lesser extent (13.0 +/- 5.0 degrees  vs
      15.8 +/- 4.5 degrees  at 40% of maximal aerobic power, P < .05). The increase in
      LV untwisting rates during exercise was also lower in children, leading to a
      lower percentage of untwisting during early diastole (8 +/- 8% vs 29 +/- 20% at
      40% of maximal aerobic power, P < .001). Consequently, during early diastole, the
      normal timing of diastolic events observed in young adults, with untwist
      occurring before radial displacement, was blunted in children. Nevertheless,
      children exhibited normal LV filling due to higher diastolic radial and
      longitudinal strain rates. CONCLUSIONS: Twist-untwist mechanics may evolve with
      advancing age. In children, early diastolic LV untwisting appears to be less
      important than in adults. Their better LV intrinsic myocardial relaxation may
      ensure adequate LV filling during exercise without dependence on the additional
      effect of suction resulting from LV energy recoil.

PMID- 23972491
TI  - Ovarian localization of 11beta-hydroxysteroid dehydrogenase (11betaHSD): effects
      of ACTH stimulation and its relationship with bovine cystic ovarian disease.
AB  - Cystic ovarian disease (COD) is an important cause of infertility in cattle, and
      ACTH has been involved in regulatory mechanisms related to ovarian function
      associated with ovulation, steroidogenesis, and luteal function. Here, we
      examined the localization of 11beta-hydroxysteroid dehydrogenase type 1
      (11betaHSD1) and 11betaHSD2 proteins in the ovary of healthy cows and animals
      with spontaneous and ACTH-induced COD and the in vitro response of the follicular
      wall exposed to ACTH. After stimulation by ACTH, we documented changes in
      11betaHSD expression and cortisol secretion by the follicular wall of large
      antral and follicular cysts. Follicular cysts showed a higher constitutive
      expression of both enzymes, whereas ACTH induced an increase in 11betaHSD1 in
      tertiary follicles and follicular cysts and a decrease in 11betaHSD2 in
      follicular cysts. Moderate expression of 11betaHSD1 was observed by
      immunohistochemistry in granulosa of control animals, with an increase (P < 0.05)
      from primary to secondary, tertiary, and atretic follicles. The level of
      immunostaining in theca interna was lower than that in granulosa. The expression
      of 11betaHSD2 was lower in the granulosa of primary follicles than in that of
      secondary, tertiary, and atretic follicles and was lower in the theca interna
      than in the granulosa. In ACTH-induced and spontaneously occurring follicular
      cysts, differences from controls were observed only in the expression of
      11betaHSD1 in the granulosa, being higher (P < 0.05) than in tertiary follicles.
      These findings indicate that follicular cysts may be exposed to high local
      concentrations of active glucocorticoids and indicate a local role for cortisol
      in COD pathogenesis and in regulatory mechanisms of ovarian function.

PMID- 23972492
TI  - Effects of incremental amounts of extruded linseed on the milk fatty acid
      composition of dairy cows receiving hay or corn silage.
AB  - The effect of supplementation of increasing amounts of extruded linseed in diets
      based on hay (H; experiment 1) or corn silage (CS; experiment 2) was investigated
      in regard to dairy performance and the milk fatty acid (FA) composition. In each
      experiment, 4 lactating multiparous Holstein cows were used in a 4 * 4 Latin
      square design (28-d periods). The cows were fed a diet (50:50 and 40:60
      concentrate:forage ratio for experiments 1 and 2, respectively; dry matter basis)
      without supplementation (H0 or CS0) or supplemented with 5% (H5 or CS5), 10% (H10
      or CS10), or 15% (H15 or CS15) of extruded linseed. Regardless of the forage
      type, diet supplementation with increasing amounts of extruded linseed had no
      effect on the dry matter intake, milk yield, or protein content or yield. In
      contrast, the milk fat content decreased progressively from H0 to H10 diets, and
      then decreased strongly with the H15 diet in response to increasing amounts of
      extruded linseed. For CS diets, the milk fat content initially decreased from CS0
      to CS10, but then increased with the CS15 diet. For the H diets, the milk
      saturated FA decreased (-24.1g/100g of FA) linearly with increasing amounts of
      extruded linseed, whereas the milk monounsaturated FA (+19.0 g/100 g),
      polyunsaturated FA (+4.9 g/100 g), and total trans FA (+14.7 g/100 g) increased
      linearly. For the CS diets, the extent of the changes in the milk FA composition
      was generally lower than for the H diets. Milk 12:0 to 16:0 decreased in a
      similar manner in the 2 experiments with increasing amounts of extruded linseed
      intake, whereas 18:0 and cis-9 18:1 increased. The response of total trans 18:1
      was slightly higher for the CS than H diets. The milk trans-10 18:1 content
      increased more with the CS than the H diets. The milk cis-9,trans-11 conjugated
      linoleic acid response to increasing amounts of extruded linseed intake was
      linear and curvilinear for the H diets, whereas it was only linear for the CS
      diets. The milk 18:3n-3 percentage increased in a similar logarithmic manner in
      the 2 experiments. It was concluded that the milk FA composition can be altered
      by extruded linseed supplementation with increasing concentrations of potentially
      health-beneficial FA (i.e., oleic acid, 18:3n-3, cis-9,trans-11 conjugated
      linoleic acid, and odd- and branched-chain FA) and decreasing concentrations of
      saturated FA. Extruded linseed supplementation increased the milk trans FA
      percentage.

PMID- 23972493
TI  - Effects of local anesthesia and flunixin meglumine on the acute cortisol
      response, behavior, and performance of young dairy calves undergoing surgical
      castration.
AB  - This study assessed the effects of flunixin meglumine (FM) and a local anesthetic
      block (LA) on postcastration performance, plasma cortisol concentration, and
      behavior in dairy calves. Thirty 2- to 3-mo-old Holstein-Friesian bull calves
      were allocated to 5 treatments: castration with LA (2% lidocaine injected into
      the testes and subcutaneously), castration with FM (1.1mg/kg, i.v.), castration
      with LA+FM, castration without drugs (CC), and sham castration (SC). Castration
      was performed using a Newberry knife and Henderson castrating tool. Feed intake
      and body weight gain were recorded for 10d postcastration. Plasma cortisol
      concentration and behavior frequency and duration were monitored for 8h
      postcastration. Variables with repeated measures were analyzed using PROC MIXED
      (SAS Institute Inc., Cary, NC); one-way ANOVA was used for nonrepeated measures.
      No differences in feed intake or body weight gain were detected among groups.
      Calves in the CC, LA, and FM groups had transient (<60, <60, and <45 min,
      respectively) increases in plasma cortisol concentration after castration, with a
      second increase at 120 min in the LA group, whereas cortisol concentration
      remained at baseline in the LA+FM and SC groups. Mean cortisol concentrations
      were lower for calves in the LA+FM and SC groups than in the CC group. The area
      under the plasma cortisol concentration curve during the first 3h postcastration
      was greater in CC- and LA-treated calves than in SC controls. Castration without
      drugs was associated with higher frequencies of crouching and statue standing and
      less oral activity compared with SC controls. Administering LA alone before
      castration was associated with higher frequencies of head turning, statue
      standing, and postural changes, and less feeding behavior compared with SC
      controls. More leg lifting to groom was seen in LA+FM-treated calves than in SC
      controls. Calves administered FM alone before castration exhibited less crouching
      than CC calves, fewer postural shifts, and more feeding behavior than LA-treated
      calves. In summary, FM alone tended to shorten the duration of cortisol response
      and reduce crouching after surgical castration. Combining LA+FM eliminated the
      cortisol response to castration but was associated with more leg lifting
      behavior. Treatment with LA alone did not mitigate the cortisol response and was
      associated with several behavioral differences compared with SC, FM-treated, or
      FM+LA-treated calves. Results suggest that LA alone did not effectively control
      discomfort in young dairy calves castrated using the Henderson castration tool.

PMID- 23972494
TI  - Short communication: Development and evaluation of predictive models of body
      weight for crossbred Holstein-Zebu dairy heifers.
AB  - Equations to predict body weight (BW) of crossbred Holstein-Zebu dairy heifers
      were developed and compared with current models (Heinrichs et al. for Holsteins,
      United States; Reis et al. for crossbred Holstein-Zebu, Brazil). The data set was
      constructed from 150 measurements of BW (320 +/- 107 kg) and biometric
      measurements such as heart girth (HG, 161 +/- 19.5 cm), withers height (WH, 126
      +/- 11.0 cm), and hip height (HH, 132 +/- 11.3 cm) of heifers from 5 commercial
      dairy producers in the southern Amazon region in Brazil. The data were evaluated
      using mixed nonlinear models with herd as a random effect. Three nonlinear
      equations were fitted: BW (kg)=0.00058.HG (cm)(2.6135); BW (kg)=0.000618.HG
      (cm)(2.7362); and BW (kg)=0.000196.HH (2.8793). An independent database was
      constructed to evaluate the models from 38 treatment means of 4 feeding trials:
      BW 258 +/- 54.3 kg, HG 142.5 +/- 11.8 cm, WH 113.2 +/- 6.0 cm, and HH 118.7 +/-
      9.1 cm (mean +/- SD). The evaluations were based on the relationship between
      observed and predicted values of BW by linear regression, root mean square
      prediction error (RMSPE), and concordance correlation coefficient analysis. Only
      the proposed model using HG accurately predicted observed BW, with bias (observed
      - predicted) of 4.83 kg and RMSPE of 5.41% of observed BW (87.7% of random
      error). The models using WH and HH failed to accurately predict observed BW, with
      a bias of -3.06 and 72.02 kg, and RMSPE of 9.40% of observed BW (75.2% of random
      error and 23.1% of systematic error) and 30.81% of observed BW (81.2% of mean
      bias). Additionally, the models of Heinrichs and Reis used for comparison did not
      predict BW accurately, with a bias of 19.32 and 29.37 kg and RMSPE of 9.08% of
      observed BW (68.4% of mean bias and 31.4% of random error) and 12.58% of observed
      BW (81.9% of mean bias). The largest concordance correlation coefficient of the
      proposed HG-nonlinear model (0.930), compared with the models of Heinrichs and
      Reis of 0.845 and 0.708, confirmed the greater accuracy and precision of the new
      equation to predict BW in crossbred Holstein-Zebu dairy heifers.

PMID- 23972495
TI  - Presence of viral and bacterial organisms in milk and their association with
      somatic cell counts.
AB  - About 20 to 35% of milk samples from cows with intramammary infection or high
      somatic cell count (SCC) are negative on bacteriological culture analysis.
      However, little is known about SCC in milk of cows infected with viruses. In the
      first part of our study, we developed a real-time PCR assay for detection of
      bovine herpesvirus (BHV) 1, BHV2, and BHV4, and bovine viral diarrhea virus
      (BVDV) in composite quarter milk samples. A total of 1,479 lactating cows of
      1,964 cows in the dairy herd were initially selected because these cows had
      complete SCC data for at least 3 consecutive test results, of which 139 lactating
      cows from different lactation age groups were selected randomly and studied
      extensively. Composite quarter milk samples were collected on 3 alternate days
      and examined for viruses, SCC, and bacteriological analysis. In total, 10, 28,
      and 0.7% of the composite quarter milk samples from cows were positive for BHV1,
      BHV2, and BHV4, respectively; BVDV was not detected in composite quarter milk
      samples. Bovine herpesvirus was not associated with a particular bacterial
      species. Our study results indicate that cows positive for BHV in composite
      quarter milk samples alone are less likely to have elevated SCC compared with
      cows with bacterial intramammary infection; BHV1, BHV2, and BHV4 are probably not
      major udder pathogens. 

PMID- 23972496
TI  - Short communication: Toxicokinetics of ochratoxin A in dairy ewes and carryover
      to milk following a single or long-term ingestion of contaminated feed.
AB  - Ruminal microbes have the capacity to inactivate ochratoxins, rendering ruminants
      less sensitive to this fungal contaminant found in cereal feeds. However,
      ochratoxin A has been reported in milk surveys. The objective of this study was
      to assess the toxicokinetics, excretion, and transmission into milk of ochratoxin
      A using doses similar to those of naturally occurring field contaminations. Six
      Lacaune dairy ewes in late lactation were separated into 2 groups that received a
      single dose of contaminated wheat containing 5 or 30 MUg of ochratoxin A/kg of
      body weight. After administration, toxicokinetics and excretion were monitored
      for 48 h. Subsequently, ewes were administered the corresponding toxin dose daily
      for 24 d followed by a second toxicokinetics and excretion monitoring period for
      this long-term exposure. The doses used did not affect production or health of
      ewes. After a single dose, ochratoxin A and its main metabolite, ochratoxin
      alpha, were found in blood 1h postexposure. The maximum blood concentrations of
      ochratoxin A and alpha, respectively, were dose dependent and were observed, on
      average, 6 and 8h after exposure. Long-term exposure increased the maximum
      concentration of ochratoxin A detected in blood, whereas ochratoxin alpha was not
      affected. In contrast, the time to reach the maximum concentration was reduced to
      3h for both molecules. Ochratoxins, essentially ochratoxin alpha, were mainly
      excreted in feces. Ochratoxin A and alpha were detected in milk at concentrations
      that were dose dependent but with a low carryover rate (<0.02%). Chronic
      administration did not increase the concentration of toxin in milk. Even though
      ochratoxin A can escape ruminal degradation and traces were found in milk of
      experimentally exposed ewes, the low carryover of ochratoxin A in milk minimizes
      the risk to consumers.

PMID- 23972497
TI  - Effect of hydrostatic high-pressure processing on the chemical, functional, and
      rheological properties of starter-free Queso Fresco.
AB  - Queso Fresco (QF), a popular high-moisture, high-pH Hispanic-style cheese sold in
      the United States, underwent high-pressure processing (HPP), which has the
      potential to improve the safety of cheese, to determine the effects of this
      process on quality traits of the cheese. Starter-free, rennet-set QF
      (manufactured from pasteurized, homogenized milk, milled before hooping, and not
      pressed) was cut into 4.5- * 4.5- * 15-cm blocks and double vacuum packaged.
      Phase 1 of the research examined the effects of hydrostatic HPP on the quality
      traits of fresh QF that had been warmed to a core temperature of 20 or 40 
      degrees C; processed at 200, 400, or 600 MPa for 5, 10, or 20 min; and stored at
      4  degrees C for 6 to 8d. Phase 2 examined the long-term effects of HPP on
      quality traits when QF was treated at 600 MPa for 3 or 10 min, and stored at 4 or
      10  degrees C for up to 12 wk. Warming the QF to 40  degrees C before packaging
      and exposure to high pressure resulted in loss of free whey from the cheese into
      the package, lower moisture content, and harder cheese. In phase 2, the control
      QF, regardless of aging temperature, was significantly softer than HPP cheeses
      over the 12 wk of storage. Hardness, fracture stress, and fracture rigidity
      increased with length of exposure time and storage temperature, with minor
      changes in the other properties. Queso Fresco remained a bright white, weak
      bodied cheese that crumbled and did not melt upon heating. Although high
      pressures or long processing times may be required for the elimination of
      pathogens, cheese producers must be aware that HPP altered the rheological
      properties of QF and caused wheying-off in cheeses not pressed before packaging.

PMID- 23972498
TI  - Management of psoriasis in patients treated with anti-TNF-alpha therapy for
      inflammatory bowel disease.

PMID- 23972499
TI  - Preparation of multicompartment sub-micron particles using a triple-needle
      electrohydrodynamic device.
AB  - Control over the size and morphology of polymeric carriers for drug delivery
      systems is essential to optimize their functionality. In the current study, we
      demonstrate the feasibility of using an electrohydrodynamic process with a triple
      needle device to prepare nearly mono-dispersed, spherical, tri-layered sub-micron
      particles. Three biocompatible polymer solutions of poly (lactic-co-glycolic
      acid) (PLGA), polycaprolactone (PCL) and polymethylsilsesquioxane (PMSQ) were
      used to prepare particles with three distinct layers. Optimized particles were
      shown to be spherical with an average size ranging from 320 nm (+/-80 nm) to 220
      (+/-8 nm), which varied with a change in the working distance in the
      electrohydrodynamic processing. The surface and internal structure and morphology
      were studied using confocal, transmission and scanning electron microscopy
      combined with focused ion beam sectioning. Cytotoxicity was shown to be
      negligible in an in vitro assay. The ability to fabricate such multilayered
      particles in a single step, under ambient conditions has considerable potential
      for a range of applications in particular controlled release drug delivery
      system.

PMID- 23972500
TI  - Interfacial behaviour of sodium stearoyllactylate (SSL) as an oil-in-water
      pickering emulsion stabiliser.
AB  - The ability of a food ingredient, sodium stearoyllactylate (SSL), to stabilise
      oil-in-water (O/W) emulsions against coalescence was investigated, and closely
      linked to its capacity to act as a Pickering stabiliser. Results showed that
      emulsion stability could be achieved with a relatively low SSL concentration
      (>=0.1 wt%), and cryogenic-scanning electron microscopy (cryo-SEM) visualisation
      of emulsion structure revealed the presence of colloidal SSL aggregates adsorbed
      at the oil-water interface. Surface properties of SSL could be modified by
      altering the size of these aggregates in water; a faster decrease in surface
      tension was observed when SSL dispersions were subjected to high pressure
      homogenisation (HPH). The rate of SSL adsorption at the sunflower oil-water
      interface also increased after HPH, and a higher interfacial tension (IFT) was
      observed with increasing SSL concentration. Differential scanning calorimetry
      (DSC) enabled a comparison of the thermal behaviour of SSL in aqueous dispersions
      with SSL-stabilised O/W emulsions. SSL melting enthalpy depended on emulsion
      interfacial area and the corresponding DSC data was used to determine the amount
      of SSL adsorbed at the oil-water interface. An idealised theoretical interfacial
      coverage calculation based on Pickering emulsion theory was in general agreement
      with the mass of SSL adsorbed as predicted by DSC.

PMID- 23972501
TI  - Role of relative size of asperities and adhering particles on the adhesion force.
AB  - Adhesion force between silica microspheres of different sizes and different rough
      surfaces (silicon and diamond like carbon) has been measured with an atomic force
      microscope (AFM). Surface roughness, asperity geometry, and size of adhering
      particles play an important role in determining the adhesion force. Adhesion
      force linearly increases with size of adhering particle for smooth surfaces and
      can be described by the JRK model. Adhesion force of adhering particle bigger
      than in size to the asperities decreases with surface roughness and can be
      described by the Rabinovich model. For the particles smaller than or similar in
      size to the asperities, the adhesion force increases with surface roughness. In
      later case, the interaction of adhering particles with valley portion of
      asperities is dominated and the contact area increases. On the basis of
      Rabinovich model, a new equation, which takes the relative size of adhering
      particles and asperities into account, is derived and compared with experimental
      results. The normalized adhesion force decreases with ratio of root-mean-square
      (rms) roughness to radius of adhering particle up to 0.0025, followed by
      increasing normalized adhesion forces. 

PMID- 23972502
TI  - Removal of lead (Pb2+) from aqueous medium by using chars from co-pyrolysis.
AB  - The effectiveness of chars from the co-pyrolysis of pine, used tires and plastic
      wastes for the removal of lead (Pb(2+)) from aqueous medium, was investigated.
      The chars were predominantly of macroporous nature, but the introduction of tires
      in the pyrolysis feedstock enhanced their mesoporous content as well as surface
      area. Pb(2+) sorption with the chars was a slow and unstable process in which
      sorption-desorption seems to be competing. The highest Pb(2+) removal (88%) was
      attained by the char resulting from the pyrolysis of a mixture composed by equal
      mass ratios of used tires and plastics, at 48 h of contact time. This char was
      also the one with the overall better performance for Pb(2+) sorption, achieving
      almost 100% of Pb(2+) removal on the study of the effect of adsorbent dose.
      Mixing the three raw materials for pyrolysis had no advantage for the resulting
      char concerning the removal efficiency of Pb(2+). The sorption mechanisms varied
      according to the pyrolysis feedstock: in chars from feedstock with pine,
      chemisorption involving complexation with oxygenated surface functional groups
      followed by cation exchange was the presumable mechanism. In tire rubber derived
      chars, cation exchange with Ca(2+), K(+), and Zn(2+) played the major role on
      Pb(2+) sorption.

PMID- 23972503
TI  - One-pot solvothermal synthesis of graphene-supported TiO2 (B) nanosheets with
      enhanced lithium storage properties.
AB  - A facile process was developed for the synthesis of graphene-supported TiO2 (B)
      nanosheets (GTBN) composite based on the hydrothermal treatment titanium (III)
      chloride and graphene oxide in an ethylene glycol. The morphology and
      microstructure of the composites were examined by X-ray diffraction, X-ray
      photoelectron spectroscopy, transmission electron microscopy, and Raman
      spectroscopy. The obtained GTBN show a high thermal stability and the phase
      transformation of TiO2 (B) to anatase can be prevented by graphene after
      pyrolysis of GTBN at 350 degrees C for 2h. Furthermore, GTBN exhibited high rate
      performance and stability of lithium ion batteries, due to the enhanced
      conductivity of the electrode and accommodation to volume/strain changes during
      lithium insertion-extraction. 

PMID- 23972504
TI  - Serratus anterior muscle activation during knee push-up plus exercise performed
      on static stable, static unstable, and oscillating unstable surfaces in healthy
      subjects.
AB  - OBJECTIVES: To compare electromyographic (EMG) activity of the serratus anterior
      (SA) during knee push-up plus exercises according to various surfaces (static
      stable, static unstable, and oscillating unstable surfaces). STUDY DESIGN:
      Comparative study by repeated measures. SETTING: Yonsei University laboratory.
      PARTICIPANTS: In total, 15 healthy male subjects participated. MAIN OUTCOME
      MEASURES: The subjects performed knee push-up plus exercises on three different
      surfaces: static stable, static unstable, and oscillating unstable surfaces.
      Surface EMG activity of the SA for the peak and average amplitudes were collected
      from the dominant arm and presented as a percentage of the maximal voluntary
      contraction. A one-way repeated-measures ANOVA with a Bonferroni post hoc test
      was performed to compare differences in SA EMG activity according to the surface.
      RESULTS: The peak and average amplitudes of SA activity were significantly
      greater during knee push-up plus on the oscillating unstable surface than on the
      static stable or static unstable surfaces (p < 0.01). Additionally, there was no
      significant difference between the stable and static unstable surfaces (p >
      0.05). CONCLUSIONS: Knee push-up plus exercise on an oscillating unstable surface
      activates the SA more than the same exercise on static stable and static unstable
      surfaces.

PMID- 23972505
TI  - Internal sphincterotomy versus topical nitroglycerin ointment for chronic anal
      fissure.
AB  - BACKGROUND: Anal fissure is a common benign condition. An anorectal problem is
      defined as a split in the anal canal mucosa that extends from the dentate line to
      the anal verge. Chronic anal fissure is defined by a history of symptoms present
      for more than 2 months' duration and with a triad of external skin tags, namely,
      a hypertrophied anal papilla, an ulcer with rolled edges, and a base exposing the
      internal sphincter. Because complications such as incontinence are associated
      with surgical treatment, chemical sphincterotomy is currently favored.
      OBJECTIVES: The objective of this study is to compare the difference in outcome
      between open partial lateral anal sphincterotomy and application of topical 0.2%
      nitroglycerin ointment for the treatment of chronic anal fissure. METHODS: This
      was a quasi-experimental study carried out between January 16, 2007 and January
      15, 2008 in the Surgical Department of Jinnah Hospital, Lahore, Pakistan. Sixty
      consecutive cases with a clinical diagnosis of chronic anal fissure were
      recruited in the study. All recruited patients met the study inclusion criteria
      and were randomly assigned to one of the two groups. Group A was managed
      conservatively using topical 0.2% nitroglycerin ointment, whereas Group B
      underwent open partial lateral anal sphincterotomy. Both groups were followed up
      at 1 week, 2 weeks, 4 weeks, and 6 weeks after the treatment. RESULTS: All the
      patients complained of pain. A total of 43 (71.7%) patients had pain with
      constipation, whereas 31 (51.7%) patients had bleeding per rectum. Upon
      clinically examining the anal area, tenderness was elicited in all 60 (100%)
      patients. Group A included 30 (11 females and 19 males) cases treated with
      topical 0.2% nitroglycerin ointment and Group B included 30 (11 females and 19
      males) cases who underwent open partial lateral anal sphincterotomy. In Group A,
      only 15 patients with fissures were successfully treated (50%). By contrast, 28
      (93%) patients with fissures in Group B were successfully treated, and only two
      (7%) remained uncured. These two patients (6.6%) in Group B suffered from
      incontinence due to flatus and feces as a complication of the procedure.
      CONCLUSION: This quasi-experimental study demonstrates that open partial lateral
      internal sphincterotomy is superior to topical 0.2% nitroglycerin application in
      the treatment of chronic anal fissure, with good symptomatic relief, high rate of
      healing, fewer side effects, and a very low rate of early continence
      disturbances.

PMID- 23972506
TI  - Treatment of sternal wound infections after open-heart surgery.
AB  - OBJECTIVE: The aim of this study was to investigate the proper treatment of
      infected median sternotomy wounds. METHODS: A retrospective study was conducted
      to investigate the proper treatment of infected median sternotomy wounds on
      patients with sternal wound infections from January 2007 to July 2009. The
      characteristics of the sternal infections and the treatment outcomes were
      analysed. RESULTS: Ninety-seven patients with sternal wound infections were
      treated. A total of 32 patients acquired the infection within one month after
      open-heart surgery, 10 patients got the infection one to two months after the
      surgery, and 1 patient died two days after debridement. There were 54 patients
      who acquired the infection beyond two months post-surgery, while 1 patient died
      on the day before the operation. One patient received four cycles of wound
      debridement, 18 patients received two cycles and 78 patients only received one
      cycle. A total of 14 patients received a vacuum-assisted closure treatment. There
      were 73 patients who had surgery for repair of muscle flaps, 1 patient for breast
      tissue flap, 63 patients for pectoralis major muscle flap, and 9 patients with
      rectus abdominis muscle flap. There were 12 patients who received a transverse
      plate fixation of the sternum with titanium plating. CONCLUSION: A positive
      prognosis can be obtained by the algorithm treatment based on the onset and depth
      of the sternal infection.

PMID- 23972507
TI  - Goldilocks mastectomy for obese Japanese females with breast ptosis.
AB  - The Goldilocks mastectomy is a method that uses redundant mastectomy flap tissue
      alone to create a breast mound in female American patients with macromastia.
      Goldilocks mastectomy was performed for obese Japanese females with breast
      ptosis, and its indications were considered for Japanese female patients. This
      report presents the results of five patients who underwent Goldilocks mastectomy,
      including one with bilateral breast cancer. The average age of the patients was
      72 years (range: 67-76 years). The body mass index (BMI) was more than 25 in all
      the cases. Four patients had invasive ductal carcinoma, and one patient had
      noninvasive ductal carcinoma of bilateral breasts. The cosmetic results were
      found to be good in two cases [a patient with bilateral breast cancer and a
      severely obese patient (BMI = 39)]. The cosmetic results in the other three cases
      were poor. Although the reconstructed breast size was small, this procedure
      resulted in better cosmetic results than what would be achieved with the usual
      method of mastectomy for Japanese patients with bilateral breast cancer and
      severely obese Japanese patients. 

PMID- 23972508
TI  - Nevus anemicus in neurofibromatosis type 1: a potential new diagnostic criterion.
AB  - BACKGROUND: Children with multiple cafe-au-lait macules (CALMs) may be followed
      for years before a second National Institutes of Health clinical criterion of
      neurofibromatosis type 1 (NF1) develops to confirm the diagnosis. OBJECTIVE: We
      sought to assess the prevalence of nevus anemicus (NA) in NF1 and its association
      with neuro-ophthalmologic complications. METHODS: This was a prospective
      multicenter case-control study of 210 consecutive patients with multiple CALMs.
      Patients with NF1 were matched for age, sex, and center with control subjects. We
      documented the number, location, and morphologic appearance of NA; dermatologic
      features of NF1; magnetic resonance imaging results; and family history. RESULTS:
      In all, 77 (51%) patients with NF1 had NA compared with 6 (2%) control subjects.
      NA was not detected in 26 patients with other genodermatoses associated with
      CALMs. Patients with NF1 and NA were younger than those without NA (median age:
      17 years) (P = .002). NA was mostly localized to the upper anterior aspect of the
      chest. NA was not significantly linked with other clinical manifestations of NF1,
      including optic glioma and unidentified bright objects. LIMITATIONS: A potential
      referral bias associated with tertiary care centers is a limitation. CONCLUSIONS:
      NA appears to have a high prevalence and specificity in NF1 and might serve as a
      marker for NF1 in children with multiple CALMs.

PMID- 23972509
TI  - Evaluation of essential clinical components and features of current acne global
      grading scales.
AB  - BACKGROUND: Acne research is hindered by the absence of a universal, consistently
      applied standard for severity grading. Acne experts recently identified 4
      essential clinical components and 2 features for an ideal acne global grading
      scale (AGGS). OBJECTIVE: This study evaluated current AGGSs against consensus
      criteria previously identified as necessary. METHODS: AGGSs were identified by
      systematic literature search and then evaluated independently by 4 raters against
      criteria (components and subcomponents; features and subfeatures) identified as
      essential. RESULTS: Eighteen AGGSs fulfilled selection criteria. Three scored 1
      full SD above the mean for categorical scores. We also identified highest-ranked
      AGGSs for subcategory scores. LIMITATIONS: Only English-language scales were
      selected. Efficiency and acceptance were not evaluable. CONCLUSION: Although no
      singular scale fulfilled all essential criteria, this study did identify highly
      ranked AGGSs. Incorporation and rationalization of their components and features
      should facilitate development of an ideal standard.

PMID- 23972510
TI  - Amelanotic acral melanomas: clinicopathological, BRAF mutation, and KIT
      aberration analyses.
AB  - BACKGROUND: Amelanotic acral melanoma (AAM) is very rare and difficult to
      diagnose both clinically and pathologically. Complete-type AAM shows no black to
      brown pigmentation in the lesion, whereas incomplete-type AAM shows focal or
      subtle pigmentation. AAM has been the subject of few investigations. OBJECTIVES:
      We analyzed the clinicopathological features, BRAF mutations, and KIT aberrations
      in 35 Korean AAM cases. METHODS: We included 28 cases of complete-type and 7
      cases of incomplete-type AAM. RESULTS: In all, 26 AAMs (45.7%) were located on
      the feet of patients, 21 of which (82.9%) showed ulceration. Sixteen cases
      developed in subungual areas. Nodular melanoma was the most common
      histopathological subtype (63.6%). The most frequent cell types affected were
      epithelioid and spindled. HMB-45 staining was strongly positive in 66.7% of AAMs;
      4 (12.1%) were negative for HMB-45, and 3 of these were complete-type AAMs. Of 33
      total patients, BRAF mutations were detected in 2 AAM cases, and KIT aberrations
      were present in 11 cases (33.3%). Four cases (12.1%), all of which were complete
      type AAMs, had KIT mutations. KIT aberrations were weakly correlated with c-kit
      staining. Twenty patients were TNM stage I or II, and mean survival was 30.14 +/-
      4.54 months. LIMITATIONS: The study is limited by the small number of patients.
      CONCLUSION: Physicians should be aware of rare and hard-to-diagnose AAMs. We
      expect that tyrosine kinase inhibitors would be effective for KIT-mutated
      patients with complete-type AAMs.

PMID- 23972511
TI  - Gait and jogging parameters in people with minimally impaired multiple sclerosis.
AB  - Increasing awareness of the significance of ambulatory limitations in people with
      multiple sclerosis (MS) requires a regular assessment of walking ability in order
      to monitor disease dynamics. However, it is questionable whether the standard
      tools are sufficiently sensitive to detect mobility deficits in patients who are
      minimally impaired. Therefore, the main objective of this study was to examine an
      extended assessment tool characterizing spatio-temporal parameters of gait and
      jogging in people with minimally impaired MS. Twenty relapsing remitting patients
      diagnosed with MS, 8 women and 12 men, aged 36.3 +/- 9.2 y, EDSS mean score 1.8
      +/- 1.2, were recruited from the Multiple Sclerosis Center, Sheba Medical Center,
      Tel Hashomer, Israel to participate in the study. Twenty apparently healthy
      subjects (10 women and 10 men), aged 34.3 +/- 7.4 years served as controls.
      Balance-, gait- and jogging-related spatio-temporal parameters were obtained
      using the Zebris FDM-T Treadmill (Zebris((r)) Medical GmbH, Germany). Each
      subject completed a sequence of 3 jogging tests under different conditions. Gait
      and balance tests were performed prior and after jogging trials. When comparing
      gait evaluation, jogging revealed additional abnormalities in the MS group vs.
      the healthy controls. In addition to step time asymmetry and larger step width,
      jogging was associated with a slower self-selected velocity, shorter step length,
      longer stance phase and a prolonged double support phase. People minimally
      affected by MS have the ability to jog. However, clinician's should be aware of
      the possible deficits accompanying this popular activity.

PMID- 23972513
TI  - Silicification of auxospores in the araphid diatom Tabularia fasciculata
      (Bacillariophyta).
AB  - We report on auxospore wall structure and development in the araphid pennate
      diatom Tabularia fasciculata. Similar to most other pennates, these auxospores
      showed a typical bidirectional elongation, but unexpectedly bore no transverse
      perizonium, and with no detectable silicon during much of their expansion. Energy
      dispersive X-ray spectroscopy (EDS) analyses segregated auxospores into two
      types: (1) those containing no detectable silicon and (2) those with measureable
      amounts. Both types were of similar size. Silica precipitation began throughout
      the auxospore at or near maximal length, but initially was detectable in isolated
      regions throughout the structure. Following this initial condition, silicon was
      consistently detectable throughout auxospores of comparable size and corresponded
      to deposition of longitudinal perizonium (visible through the thin organic outer
      layer of the wall in some auxospores), followed by the deposition of the initial
      valves. Our results raise the question as to how the tubular shape of
      bidirectionally expanding auxospores up to ~90 MUm long is maintained in the
      absence of transverse siliceous elements restricting isodiametric expansion of
      the cell, which are present in all other known pennate auxospores and all but one
      other diatom. Our study is the first to systematically examine mineral elements
      of the auxospore wall analytically.

PMID- 23972512
TI  - Introducing a new definition of a near fall: intra-rater and inter-rater
      reliability.
AB  - Near falls (NFs) are more frequent than falls, and may occur before falls,
      potentially predicting fall risk. As such, identification of a NF is important.
      We aimed to assess intra and inter-rater reliability of the traditional
      definition of a NF and to demonstrate the potential utility of a new definition.
      To this end, 10 older adults, 10 idiopathic elderly fallers, and 10 patients with
      Parkinson's disease (PD) walked in an obstacle course while wearing a safety
      harness. All walks were videotaped. Forty-nine video segments were extracted to
      create 2 clips each of 8.48 min. Four raters scored each event using the
      traditional definition and, two weeks later, using the new definition. A fifth
      rater used only the new definition. Intra-rater reliability was determined using
      Kappa (K) statistics and inter-rater reliability was determined using ICC. Using
      the traditional definition, three raters had poor intra-rater reliability
      (K<0.054, p>0.137) and one rater had moderate intra-rater reliability (K=0.624,
      p<0.001). With the traditional definition, inter-rater reliability between the
      four raters was moderate (ICC=0.667, p<0.001). In contrast, the new NF definition
      showed high intra-rater (K>0.601, p<0.001) and excellent inter-rater reliability
      (ICC=0.815, p<0.001). A priori, it is easy to distinguish falls from usual
      walking and NFs, but it is more challenging to distinguish NFs from obstacle
      negotiation and usual walking. Therefore, a more precise definition of NF is
      required. The results of the present study suggest that the proposed new
      definition increases intra and inter-rater reliability, a critical step for using
      NFs to quantify fall risk.

PMID- 23972514
TI  - Morphology and morphogenesis of Apoholosticha sinica n. g., n. sp. (Ciliophora,
      Hypotrichia), with consideration of its systematic position among urostylids.
AB  - This paper investigates the morphology, morphogenesis and SSU rRNA gene-based
      phylogeny of Apoholosticha sinica n. g., n. sp., isolated from mangrove wetland
      in Shenzhen, southern China. The new genus Apoholosticha is characterized by its
      bipartite adoral zone, clearly differentiated frontal cirri arranged in a
      bicorona, midventral complex composed of midventral pairs only, one marginal
      cirral row on each side, presence of frontoterminal and transverse cirri, and the
      lack of a buccal cirrus and caudal cirri. The type species, Apoholosticha sinica
      n. sp. is diagnosed by the elongated body shape and two kinds of cortical
      granules. Its main morphogenetic features are similar to that of Pseudokeronopsis
      except for (1) no buccal cirrus is formed and (2) its macronuclear nodules fuse
      into a single mass during cell division. Phylogenetic analyses for the new taxon
      indicate that Apoholosticha n. g. is most closely related to Nothoholosticha and
      Heterokeronopsis, and falls into the family Pseudokeronopsidae within the core
      Urostylida clade. In addition, a species that had been misidentified in previous
      literature is here recognized and assigned to the new genus as Apoholosticha
      sepetibensis (Wanick and Silva-Neto, 2004) n. comb. (basionym: Pseudokeronopsis
      sepetibensis Wanick and Silva-Neto, 2004).

PMID- 23972515
TI  - [Nerve stimulation is not obsolete yet].

PMID- 23972516
TI  - [Temporary epicardial pacing following cardiac surgery: practical aspects].
AB  - OBJECTIVES: To review the practical aspects of temporary epicardial pacing
      following open heart surgery. METHODS: Review of articles published in English or
      French within the last five years and investigating temporary epicardial pacing
      (indications, pacing modes, epicardial wires and temporary generators). The
      studies were extracted from the databases ScienceDirect and Pubmed. RESULTS:
      Temporary epicardial pacing is used to treat severe conduction and/or rhythm
      disorders, but also to improve hemodynamics by optimizing selected temporary
      pacing settings. Temporary epicardial pacing consists in choosing the most
      suitable pacing mode according to the situation (surgery, patient, conduction
      and/or rhythm abnormalities) and setting its parameters that ensure : i) optimal
      pacemaker functioning; ii) epicardial electrodes longevity; iii) the most
      favorable hemodynamic profiles. Management of temporary pacing settings and their
      regular adjustment, at least daily and based on thresholds, are part of good
      clinical practices. Nevertheless, the French literature lacks official
      recommendations for temporary epicardial pacing. CONCLUSION: Temporary epicardial
      pacing following cardiac surgery is a simple method, more effective than
      transcutaneous pacing and easier to implement than transvenous pacing. Its
      practical management should be known by all physicians (anesthetists, cardiac
      surgeons) as well as paramedical personnel in order to avoid the risks of
      suboptimal functioning. A good practice protocol is proposed at the end of the
      manuscript.

PMID- 23972517
TI  - Wnt5a enhances the response of CML cells to Imatinib Mesylate through JNK
      activation and gamma-catenin inhibition.
AB  - Imatinib Mesylate is widely used for the treatment of chronic myelogenous
      leukaemia (CML), and its effects on CML cells are influenced by several
      signalling proteins. The research is aimed at determining whether Wnt5a affects
      the effects of Imatinib Mesylate against BCR-ABL positive CML cells (K562 cells
      and KU812 cells) and which signalling proteins are involved in. The results
      showed that Wnt5a augmented the effects of Imatinib Mesylate on inhibiting CML
      cells proliferation and inducing apoptosis in vitro; Wnt5a enhanced the
      inhibition effect of Imatinib Mesylate on the growth of K562 cells xenograft
      tumour in an animal model. Furthermore, Wnt5a inhibited beta-catenin and its
      target gene Survivin, increased the activity of JNK and suppressed gamma-catenin
      expression. When inhibiting the activity of JNK, the influence of Wnt5a on the
      effects of Imatinib Mesylate was attenuated. Moreover, JNK suppressed beta
      catenin and its target gene Survivin, and enhanced the effects of Imatinib
      Mesylate. These results suggest that Wnt5a can enhance the efficacy of Imatinib
      Mesylate through JNK/beta-catenin/Survivin and gamma-catenin/beta
      catenin/Survivin pathways. 

PMID- 23972518
TI  - Changes in hand hygiene compliance after a multimodal intervention and
      seasonality variation.
AB  - BACKGROUND: Hand hygiene is the most important measure to reduce health care
      related infections and colonization with multiresistant micro-organisms. We
      sought to determine the rate and seasonality of handwashing compliance in a
      university-affiliated hospital. METHODS: In January 2006 (baseline period),
      handwashing observation was first made in an intensive care unit. From March to
      May 2006, there was an intervention period; and, from June 2006 to August 2009,
      we followed hand hygiene compliance. Seasonality curves for handwashing
      compliance were made during follow-up period. RESULTS: During baseline period, a
      total of 166 observations was made. During follow-up, 17,664 opportunities for
      hand hygiene were observed. Compliance improved from 30.0% to a mean of 56.7%
      after the intervention (P < .001). The highest mean rate of compliance was 77.9%
      for nurses, compared with 52.6% for technicians (P < .001) and 44.6% for
      physicians (P < .001). Compliance was lower during summer days (first trimester
      of the year) and increased after March and April and slowly decreased through the
      end of the year. CONCLUSION: One of the reasons for the lower handwashing
      compliance in the first 3 months of the year is that, in Brazil, this is the
      summer vacation time; and, because of that, the staff's workload and the number
      of less well-trained personnel are higher. We emphasize the importance of
      continuously monitoring hand hygiene to determine the seasonal aspects of
      compliance.

PMID- 23972519
TI  - Healthcare-associated infections studies project: an American Journal of
      Infection Control and National Healthcare Safety Network data quality
      collaboration-Ventilator-associated event 1, 2013.
AB  - This is the second case study published in a series in AJIC since the Centers for
      Disease Control and Prevention/National Healthcare Safety Network (NHSN)
      surveillance definition update of 2013. These cases reflect some of the complex
      patient scenarios Infection Preventionists (IP) have encountered in their daily
      surveillance of health care-associated infections (HAI) using NHSN definitions.
      This is the first case utilizing the new NHSN Ventilator-associated Events (VAE)
      module and criteria. 

PMID- 23972520
TI  - Single-center trials tend to provide larger treatment effects than multicenter
      trials: a systematic review.
AB  - OBJECTIVES: To assess whether the reported trial characteristics are associated
      with treatment effects on all-cause mortality within critical care medicine.
      STUDY DESIGN AND SETTING: We identified all eligible randomized controlled trials
      (RCTs) from Cochrane Reviews on patients with sepsis, septic shock, and
      cardiogenic shock. Risk of bias was judged on 12 trial characteristics, including
      the differentiation between single-center and multicenter trials. Hierarchical
      random-effects models quantified the impact of the risk of bias items on the
      reported effect estimates of mortality. RESULTS: Twelve meta-analyses that
      involved 82 RCTs were selected and judged. Single-center trials estimated a
      significant larger treatment effect compared with multicenter trials (ratio of
      odds ratios, 0.64; 95% confidence interval: 0.47, 0.87). Treatment effect tended
      to be overestimated with selective reporting of preplanned end points. Biases in
      different trial characteristics are unlikely to operate independently and may
      have modified these associations. CONCLUSION: The results of this study highlight
      a substantial difference in treatment effect estimates between single-center and
      multicenter trials. Therefore, we recommend that results from single-center
      trials should be cautiously used for decision making.

PMID- 23972521
TI  - The z-difference can be used to measure covariate balance in matched propensity
      score analyses.
AB  - OBJECTIVES: The propensity score (PS) method is increasingly used to assess
      treatment effects in nonrandomized trials. Although there are several methods to
      use the PS for analysis, matching treated and untreated patients by the PS is
      recommended by most researchers among other reasons because this allows assessing
      covariate balance before and after matching. Although the standardized difference
      is commonly applied to compute a measure of balance, it has two deficiencies: its
      distribution depends on the sample size and one cannot compare standardized
      differences for baseline covariates on different scales, that is, continuous,
      binary, ordinal, or nominal covariates. STUDY DESIGN AND SETTING: We introduce
      the z-difference to measure covariate balance in matched PS analyses and
      illustrate it by a recent matched PS analysis from cardiac surgery. RESULTS: The
      z-difference is simple to calculate, can be used with second moments for
      continuous covariates, and in most cases can also be computed from published
      data. Its full advantage emerges after displaying z-differences in a Q-Q plot,
      which allows balance comparisons with respect to (1) a randomized trial and (2) a
      perfectly matched PS analysis in the sense of Rubin and Thomas. CONCLUSION: The z
      difference can be used to measure covariate balance in matched PS analyses.

PMID- 23972522
TI  - Re: Gunter Niegisch, Anja Lorch, Michael J. Droller, Hugh J. Lavery, Kristian D.
      Stensland, Peter Albers. Neoadjuvant chemotherapy in patients with muscle
      invasive bladder cancer: which patients benefit? Eur Urol 2013;64:355-7.

PMID- 23972523
TI  - Are we ready for molecular imaging-guided surgery?

PMID- 23972524
TI  - Early salvage radiotherapy following radical prostatectomy.
AB  - CONTEXT: Depending on the pathologic tumour stage, up to 60% of prostate cancer
      patients who undergo radical prostatectomy will develop biochemical relapse and
      require further local treatment. OBJECTIVES: We reviewed the results of early
      salvage radiation therapy (RT), defined as prostate-specific antigen (PSA) values
      prior to RT <= 0.5 ng/ml in the setting of lymph node-negative disease. EVIDENCE
      ACQUISITION: Ten retrospective studies, including one multicentre analysis, were
      used for this analysis. Among them, we received previously unpublished patient
      characteristics and updated outcome data from five retrospective single-centre
      trials to perform a subgroup analysis for early salvage RT. EVIDENCE SYNTHESIS:
      Patients treated with early salvage RT have a significantly improved biochemical
      recurrence-free survival (BRFS) rate compared with those receiving salvage RT
      initiated after PSA values are >0.5 ng/ml. Similarly, within the cohort of
      patients with pre-RT PSA values <0.5 ng/ml, improved BRFS rates were noted among
      those with lower rather higher pre-RT PSA levels. It is possible that higher RT
      dose levels and the use of adjunctive androgen-deprivation therapy improve
      biochemical control outcomes in the salvage setting. CONCLUSIONS: Based on a
      literature review, improved 5-yr BRFS rates are observed for patients who receive
      early salvage RT compared with patients treated with salvage RT with a pre-RT PSA
      value >0.5 ng/ml. Whether the routine application of early salvage RT in patients
      with initially undetectable PSA levels will be associated with demonstrable
      clinical benefit awaits the results of ongoing prospective trials.

PMID- 23972525
TI  - Medical comorbidities but not interventions adversely affect survival in patients
      with intermittent claudication.
AB  - OBJECTIVE: Intermittent claudication (IC) is common and associated with decreased
      survival. While patients with IC infrequently progress to critical limb ischemia
      (CLI), many elect to pursue intervention initially or during follow-up. However,
      controversy exists as to whether intervention in patients with IC adversely
      impacts survival or limb salvage. The purpose of this study was to characterize
      patient demographics and comorbidities with respect to differences in survival
      and limb salvage among patients who elect no intervention (NI) vs those electing
      immediate intervention (II) or delayed intervention (DI) for IC. METHODS:
      Patients referred to a university practice for limb ischemia were identified via
      a query of the electronic medical record from 2007 to 2011. Patients with prior
      lower extremity interventions or CLI were excluded. IC patients were classified
      according to intervention: NI during follow-up, II, and DI. Patient demographics,
      Charlson morbidity index, survival, and reintervention rates were analyzed.
      RESULTS: A total of 262 of 1320 patients met inclusion criteria. Thirty patients
      with possible IC were believed to have nonarterial related symptoms. Study
      patients included 132 with NI, 62 with II, and 38 with DI. DI patients were
      younger and less frequently diabetic (median age, 65.5 years, 63.5 years, 58.0
      years; P = .002; diabetes, 43.2%, 39.5%, 22.6%; P = .02 for NI, II, and DI,
      respectively). NI patients had higher Charlson comorbidity scores (P < .05).
      Hypertension, hyperlipidemia, and diabetes were associated with decreased
      survival in all groups (P < .05). Median survival was greatest for DI patients
      and least for NI patients (NI 92 months, II 95 months, DI 143 months; log-rank =
      .015). Primary patency of interventions at 1 and 5 years were equal for II and DI
      patients (1 year, II 80% vs DI 79%; 5 years, II 45% vs DI 50%; P = .9).
      Reintervention was common with rates similar between the II and DI groups (P >
      .05). Four of 38 DI patients required minor amputation for progression to CLI.
      There were no major amputations in any group. CONCLUSIONS: Progression to CLI is
      uncommon in IC. Survival of claudicants is decreased by diabetes, hypertension,
      and hyperlipidemia but not by intervention for IC. Reintervention is common in
      treated IC patients but no different among those undergoing II and DI.
      Intervention did not lead to major amputation. II or DI in IC patients does not
      affect survival or major amputation.

PMID- 23972526
TI  - Utility of direct angiosome revascularization and runoff scores in predicting
      outcomes in patients undergoing revascularization for critical limb ischemia.
AB  - OBJECTIVE: Both runoff scores and direct (DR) vs indirect revascularization (IR)
      according to pedal angiosomes have unclear impact on outcome for patients with
      critical limb ischemia (CLI). We compared DR vs IR and runoff scores in CLI
      patients undergoing infrapopliteal bypass for foot wounds. METHODS: Patients who
      had tibial/pedal bypass for a foot/ankle wound from 2005-2011 were identified and
      operations classified as DR or IR based on wound location and bypass target. A
      blinded observer reviewed angiograms for an intact pedal arch and calculated
      standard Society for Vascular Surgery (single tibial) and modified (composite
      tibial) runoff scores. Comorbidities, wound characteristics, wound healing, major
      amputation, and overall survival were determined. RESULTS: A total of 106 limbs
      were revascularized in 97 patients; 54 limbs had DR and 52 had IR, although only
      36% of wounds corresponded to a single, distinct angiosome. Wound characteristics
      and comorbidities were similar between groups. Mean standard (7.9 vs 7.2; P =
      .001) and modified (22.2 vs 20.0; P = .02) runoff scores were worse (higher
      number indicates worse runoff) in the IR vs DR groups; 33% had a complete pedal
      arch. Complete wound healing (78% vs 46%; P = .001) and time to complete healing
      (99 vs 195 days; P = .002) were superior with DR vs IR but were not influenced by
      runoff score, modified runoff score or presence of complete plantar arch. In
      multivariate models controlling for runoff score, DR remained a significant
      predictor for wound healing (odds ratio, 2.9; 95% confidence interval, 1.1-7.4; P
      = .028) and reduced healing time (hazard ratio, 2.1; 95% confidence interval, 1.2
      3.7; P = .012). Mean amputation-free survival (75 vs 71 months for DR vs IR; P =
      .82) and median survival (36 vs 33 months DR vs IR; P = .22) were not different
      for DR vs IR. CONCLUSIONS: DR according to pedal angiosomes provides more
      efficient wound healing, but is possible in only one-half of the patients and
      does not affect amputation-free or overall survival. DR is associated with
      improved runoff scores, but current runoff scores have little clinical utility in
      predicting outcomes in CLI patients.

PMID- 23972528
TI  - Necrotizing fasciitis in patients who underwent renal transplantation.
AB  - A 48-year-old man receiving renal transplantation was admitted due to bacterial
      pneumonia. Unfortunately, he developed septic shock due to Escherichia coli
      related necrotizing fasciitis (NF). To date, there have only been 11 such cases
      reported in the literature and this is the first case caused by E coli. An
      analysis of all 12 cases showed 83% of patients had the infection in the
      extremities, 27.3% of pathogens was Streptococcus pyogenes, 50% of patients had
      shock, but the mortality rate (16.7%) was no greater than that seen in non-renal
      transplant patients with NF. The elderly had higher mortality (P = .085) and
      patients taking mycophenoic acid had a higher risk of death (P = .039).

PMID- 23972527
TI  - Carotid stenting versus endarterectomy in patients undergoing reintervention
      after prior carotid endarterectomy.
AB  - BACKGROUND: Outcomes for patients undergoing intervention for restenosis after
      prior ipsilateral carotid endarterectomy (CEA) in the era of carotid angioplasty
      and stenting (CAS) are unclear. We compared perioperative results and durability
      of CAS vs CEA in patients with symptomatic or asymptomatic restenosis after prior
      CEA and investigated the risk of reintervention compared with primary procedures.
      METHODS: Patients undergoing CAS and CEA for restenosis between January 2003 and
      March 2012 were identified within the Vascular Study Group of New England (VSGNE)
      database. End points included any stroke, death or myocardial infarction (MI)
      within 30 days, cranial nerve injury at discharge, and restenosis >= 70% at 1
      year follow-up. Multivariable logistic regression was done to identify whether
      prior ipsilateral CEA was an independent predictor for adverse outcome. RESULTS:
      Out of 9305 CEA procedures, 212 patients (2.3%) underwent redo CEA (36%
      symptomatic). Of 663 CAS procedures, 220 patients (33%) underwent CAS after prior
      ipsilateral CEA (31% symptomatic). Demographics of patients undergoing redo CEA
      were comparable to patients undergoing CAS after prior CEA. Stroke/death/MI rates
      were statistically similar between redo CEA vs CAS after prior CEA in both
      asymptomatic (4.4% vs 3.3%; P = .8) and symptomatic patients (6.6% vs 5.8%; P =
      1.0). No significant difference in restenosis >= 70% was identified between redo
      CEA and CAS after prior CEA (5.2% vs 3.0%; P = .5). Redo CEA vs primary CEA had
      increased stroke/death/MI rate in both symptomatic (6.6% vs 2.3%; P = .05) and
      asymptomatic patients 4.4% vs 1.7%; P = .03). Prior ipsilateral CEA was an
      independent predictor for stroke/death/MI among all patients undergoing CEA (odds
      ratio, 2.1; 95% confidence interval, 1.3-3.5). No difference in cranial nerve
      injury was identified between redo CEA and primary CEA (5.2% vs 4.7%; P = .8).
      CONCLUSIONS: In the VSGNE, CEA and CAS showed statistically equivalent outcomes
      in asymptomatic and symptomatic patients treated for restenosis after prior
      ipsilateral CEA. However, regardless of symptom status, the risk of
      reintervention was increased compared with patients undergoing primary CEA.

PMID- 23972529
TI  - Time-dependent effects of cortisol on the contextualization of emotional
      memories.
AB  - BACKGROUND: The inability to store fearful memories into their original encoding
      context is considered to be an important vulnerability factor for the development
      of anxiety disorders like posttraumatic stress disorder. Altered memory
      contextualization most likely involves effects of the stress hormone cortisol,
      acting via receptors located in the memory neurocircuitry. Cortisol via these
      receptors induces rapid nongenomic effects followed by slower genomic effects,
      which are thought to modulate cognitive function in opposite, complementary ways.
      Here, we targeted these time-dependent effects of cortisol during memory encoding
      and tested subsequent contextualization of emotional and neutral memories.
      METHODS: In a double-blind, placebo-controlled design, 64 men were randomly
      assigned to one of three groups: 1) received 10 mg hydrocortisone 30 minutes
      (rapid cortisol effects) before a memory encoding task; 2) received 10 mg
      hydrocortisone 210 minutes (slow cortisol) before a memory encoding task; or 3)
      received placebo at both times. During encoding, participants were presented with
      neutral and emotional words in unique background pictures. Approximately 24 hours
      later, context dependency of their memories was assessed. RESULTS: Recognition
      data revealed that cortisol's rapid effects impair emotional memory
      contextualization, while cortisol's slow effects enhance it. Neutral memory
      contextualization remained unaltered by cortisol, irrespective of the timing of
      the drug. CONCLUSIONS: This study shows distinct time-dependent effects of
      cortisol on the contextualization of specifically emotional memories. The results
      suggest that rapid effects of cortisol may lead to impaired emotional memory
      contextualization, while slow effects of cortisol may confer protection against
      emotional memory generalization.

PMID- 23972530
TI  - Engineering NLR immune receptors for broad-spectrum disease resistance.
AB  - Two recent reports by Maekawa et al. and Narusaka et al. demonstrated the
      transfer of a nucleotide-binding domain and leucine-rich repeat (NLR) family of
      immune receptors into evolutionarily diverged plants without causing adverse
      fitness consequences. The applications of NLRs in engineering durable and broad
      spectrum resistance in plants are highlighted here. 

PMID- 23972531
TI  - T wave morphology changes during hemodialysis.
AB  - BACKGROUND: Risk stratification for sudden cardiac death in hemodialysis (HD)
      patients is an unmet clinical need. Non invasive electrophysiological testing is
      challenging in these patients due to their oscillating cardiovascular and
      electrolyte status induced by the intermittent HD treatment. We hypothesized that
      continuous electrocardiographic monitoring during their regular HD session can
      provide reproducible repolarisation profiles. METHODS: Continuous 12-lead digital
      electrocardiographs (ECGs) were recorded during dialysis in stable patients and
      were repeated at two-week intervals for 5 times. QRS-to-T angle (TCRT), principal
      component analysis (PCA) ratio and T wave morphology dispersion (TMD) were
      calculated every 5s in overlapping 10-s ECG segments. Serum electrolytes and
      plasma parathyroid hormone (PTH) levels were measured prior to the first
      recording. RESULTS: There were 319 acceptable recordings from 76 hemodialysed
      patients. Repeated Measures Anova showed intra-subject reproducibility of all
      descriptors. Mean PCA ratio and TMD values increased through dialysis and their
      intradialytic change correlated with heart rate changes (r = 0.305, p = 0.007 and
      r = 0.287, p = 0.012, respectively). TCRT showed a variable response to HD and
      the intradialytic change correlated positively with PTH levels (r = 0.284, p =
      0.023). CONCLUSION: Repolarisation descriptors demonstrate subject-specific
      dynamic profiles during HD. PTH has a role in dynamics of myocardial
      repolarisation. The potential clinical utility of continuous intradialytic ECGs
      for risk stratification purposes should be prospectively evaluated.

PMID- 23972532
TI  - Non-canonical roles of lysyl-tRNA synthetase in health and disease.
AB  - Lysyl-tRNA synthetase (LysRS) is a highly conserved enzyme that is part of the
      translational machinery in all living cells. Besides its canonical role in
      translation, LysRS gained additional domains and functions throughout evolution.
      These include its essential role in HIV replication and its roles in
      transcriptional regulation, cytokine-like signaling, and transport of proteins to
      the cell membrane. These diverse processes are tightly regulated through post
      transcriptional modifications, interactions with other proteins, and targeting to
      the various cell compartments. The emerging variety of tasks performed by LysRS
      may therefore be utilized by various processes and pathological conditions that
      are described in this review, and their ongoing investigation is of extreme
      importance for our understanding of basic cellular regulatory mechanisms. 

PMID- 23972533
TI  - Utilization trends of cervical artificial disc replacement during the FDA
      investigational device exemption clinical trials compared to anterior cervical
      fusion.
AB  - While anterior cervical discectomy and fusion (ACDF) is the gold standard
      surgical treatment for cervical disc disease, concerns regarding adjacent segment
      degeneration lead to the development of cervical disc arthroplasty (CDA). This
      study compares the utilization trends of CDA versus ACDF during the period of the
      Food and Drug Administration Investigational Device Exemption clinical trials
      from 2004 to 2007. The Healthcare Cost and Utilization Project Nationwide
      Inpatient Sample database was used to identify CDA and ACDF procedures performed
      in the USA between 2004 and 2007. The prevalence of CDA and ACDF procedures was
      estimated and stratified by age, sex, diagnosis, census region, payor class, and
      hospital characteristics. The average length of hospital stay, total charges, and
      costs were also estimated. The number of CDA surgeries significantly increased
      annually from 2004 to 2007 and mostly took place at urban non-teaching hospitals.
      There were no regional differences between CDA and ACDF utilization. There was no
      difference between sex or admission type between CDA and ACDF patients. ACDF
      patients were older and had more diabetes, hypertension, and chronic obstructive
      pulmonary disease. CDA patients were more likely to be discharged home and had
      shorter hospital stays but had a higher rate of deep venous thrombosis than ACDF
      patients. Significantly more CDA patients had private insurance while more ACDF
      patients had Medicare. The average cost was higher for ACDF than CDA. While ACDF
      dominated surgical intervention for cervical disc disease during the trial
      period, CDA utilization increased at a significantly greater rate suggesting
      rapid early adoption. 

PMID- 23972534
TI  - Patient preferences in an online breast reconstruction resource.

PMID- 23972535
TI  - Laparoscopically harvested omental flap for breast reconstruction in Poland
      syndrome.
AB  - BACKGROUND/PURPOSE: Poland syndrome (PS) is a congenital anomaly of the thoracic
      wall characterised by a variable degree of unilateral agenesis of pectoralis
      major and minor muscles associated with ipsilateral breast, rib and upper-arm
      anomalies. In female patients, breast reconstruction is particularly challenging
      because of cranial pectoralis muscle defects and partial or complete breast
      agenesis. Different techniques have been used to treat the thoracic anomaly,
      including the positioning of an implant, fat transfer or latissimus dorsi
      transposition, but in some cases these techniques are not feasible resulting in a
      poor reconstruction. METHODS: We present our experience in correction of the
      chest anomaly of PS in a teenage population by using a pedicled laparoscopically
      harvested omental flap (LOF) to cover a pectoral or breast prosthesis. Procedures
      were performed by a surgical team which included experienced plastic surgeons and
      general paediatric surgeons. Preoperative endocrinological and psychological
      evaluation helped to determine the best timing for the correction. RESULTS: The
      technique was adopted in 20 patients aged 14-18 years, affected by the syndrome.
      In all cases, it was possible to harvest an adequate amount of pedicled omentum
      laparoscopically. Neither significant complications nor conversions to open
      surgery occurred. The aesthetic outcome of the LOF technique was, in all cases, a
      soft, natural-looking breast and a satisfactorily corrected infraclavicular
      defect. CONCLUSIONS: The LOF technique is a valid alternative to reconstruction
      in selected PS cases. It provides a satisfactory reconstruction of the breast and
      pectoral region and corrects the infraclavicular defect by filling in the area.
      It avoids the invasiveness and morbidity of a latissimus dorsi transposition.

PMID- 23972536
TI  - Mythology to reality: case report on a giant cutaneous horn of the scalp in an
      African American female.
AB  - We present a case study of a patient with a rare and disfiguring dermatologic
      condition known as cornu cutaneum, or giant cutaneous horn (GCH). While this
      condition has been well described in people of European and Asian ancestry, its
      presence in African populations is perceived to be rare and has not been reported
      in the literature until recently. We present the case of cornu cutaneum in a
      woman of African descent, contributing to the recent evidence that this condition
      may not be as rare in African populations as believed. Etiologic factors,
      epidemiology and management are also reviewed.

PMID- 23972537
TI  - Comparison of bivalirudin with heparin versus abciximab with heparin for primary
      percutaneous coronary intervention in "Real World" practice.
AB  - OBJECTIVE: We aimed to carry out a "real world" comparison of bivalirudin plus
      unfractionated heparin (UFH) versus abciximab plus UFH in patients undergoing
      primary percutaneous coronary intervention (PPCI) for ST elevation myocardial
      infarction (STEMI). METHODS: We included patients who had abciximab or
      bivalirudin during their PPCI in our unit between Sept 2009 and Nov 2011.
      RESULTS: The study included 516 and 484 patients in the bivalirudin and abciximab
      group respectively. There were more women in the bivalirudin group (29% vs 20%, p
      0.001), while cardiogenic shock (6.4% vs 10.1%, p 0.04) and thrombectomy device
      use (76.6% vs 82%, p 0.04) were lower in the bivalirudin group. The primary
      composite end point of 30-day mortality, 30-day definite stent thrombosis or non
      CABG major bleeding was similar between the bivalirudin and abciximab groups
      (7.8% vs 9.5%, OR 0.8, 95% CI 0.5 to 1.2, p 0.4). There was also no difference in
      in-hospital mortality (4.1% vs 4.3%, p 0.9), 30-day mortality (5.2% vs 6.4%, p
      0.5), 1-year mortality (9.1% vs 9.9%, p 0.7), 30-day stent thrombosis (1% vs
      0.4%, p 0.5) and non-CABG bleeding (2.7 vs 3.7%, p 0.4) between the bivalirudin
      and abciximab group respectively. On Cox proportional hazard analysis after
      adjusting for all the co-variates, the use of bivalirudin was not a predictor of
      30-day mortality (HR 1.13, 95% CI 0.7-1.9, p 0.7). CONCLUSION: In this "real
      world" observational study, there was no significant difference in the clinical
      outcome of PPCI for patients who had abciximab or bivalirudin after initial pre
      treatment with UFH.

PMID- 23972538
TI  - Transradial interventions with the GuideLiner catheter: role of proximal vessel
      angulation.
AB  - BACKGROUND: Transradial coronary intervention (TRI) is increasingly common, but
      anatomic variations and lack of guide catheter support may increase the
      complexity of TRI. The GuideLiner catheter (Vascular Solutions, Minneapolis,MN)
      is a guide catheter extension developed to provide increased guide catheter
      support. We hypothesized that TRI cases requiring GuideLiner support would have a
      greater proximal vessel angle and increased lesion angle tortuosity. METHODS:
      This was a retrospective study reviewing 146 TRI cases performed at a single
      institution between August 2010 and June 2012. 22 cases (15%) required use of the
      GuideLiner support catheter. Procedural and angiographic characteristics of all
      cases were analyzed. Multivariable analysis and receiver operator curves (ROC)
      were used to analyze predictors of GuideLiner use. RESULTS: The indications for
      TRI were similar between both groups. Subjects who required use of the GuideLiner
      support catheter at the time of TRI were significantly older (69+/-12years vs.
      62+/-13years, p=0.03). The proximal vessel angle was significantly greater in the
      cases requiring GuideLiner support (74 degrees +/-35 degrees  vs. 37 degrees +/
      23 degrees , p<0.001). Lesion angle in the Guideliner group was also
      significantly greater (48 degrees +/-32 degrees  vs. 28 degrees +/-25 degrees ,
      p<0.001). On multivariable analysis, proximal vessel angle independently
      predicted the need for GuideLiner support (AOR 1.4 per 10 degrees , p<0.001). A
      45 degrees  proximal vessel angle predicted the need for GuideLiner use with a
      sensitivity of 73% and specificity of 74% (c-statistic 0.79). None of the
      Guideliner TRI cases required conversion to femoral access. CONCLUSIONS: TRIs
      requiring GuideLiner catheter support had significantly increased lesion
      complexity and vessel tortuosity. Proximal vessel angulation is significantly
      associated with the need for GuideLiner use during transradial intervention. Use
      of the Guideliner facilitated successful completion of PCI despite the use of a
      wide variety of guiding catheters in this series.

PMID- 23972540
TI  - Slowing progression of early stages of AD with alternative therapies: a
      feasibility study.
AB  - This pilot study identified the feasibility and efficacy of the effect of
      combining healing touch (HT) and body talk cortices (BTC) on the progression of
      Alzheimer's disease (AD). Both HT and BTC elicit the relaxation response and
      support cognitive function from two different perspectives. A two-group, repeated
      measures design was used. Subjects (n = 22), 65 or older with early stage (less
      than four) AD, residing in the community (n = 2) or in care agencies (n = 20),
      were assigned to either the HT-BTC group (n = 12) or the control group (n = 10)
      randomized by residence. The treatment group received, 6 months of weekly HT and
      performed the BTC technique daily. The usual medical regimen for all subjects was
      continued. The control group had no additional interventions. Both groups were
      assessed at baseline, 3 and 6 months. The groups did not differ significantly at
      baseline on cognitive reserve, age, gender, and ethnicity, nor on the outcome
      variables (cognitive function, mood, & depression). Adherence (76%) to the BTC
      protocol, the major feasibility problem, related to memory deficits. Significant
      interactions occurred regarding cognitive function and mood. Significant
      improvements in cognitive function (p = .008), mood (p = .001), and depression (p
      = .028) were observed in the treatment group which is not the usual course of AD.
      A decline in cognitive function occurred in the control group typical of AD's
      usual course. Although the number of subjects in this pilot study was small, and
      there were feasibility challenges with recruitment and adherence, important
      trends were noted suggesting areas for future study. 

PMID- 23972541
TI  - Delirium superimposed on Charles Bonnet syndrome: a case study.
AB  - Older adults with visual impairment may experience visual hallucinations in the
      setting of normal cognition and absence of psychiatric illness. This phenomenon
      is referred to as Charles Bonnet syndrome. Information concerning Charles Bonnet
      syndrome predominantly comes from case studies. Reassuring the person
      experiencing the hallucinations they are not suffering from psychosis constitutes
      the mainstay of treatment. What follows is the case of a vision impaired, older
      adult male with known Charles Bonnet syndrome, who, following emergency surgery
      and associated delirium while in the intensive care unit, experiences an
      aggressive change in hallucinations. Nurses need to understand the pathology and
      characteristics of Charles Bonnet syndrome in order to distinguish it from other
      pathologies underlying hallucinations. This knowledge is necessary to provide
      safe, patient-centered care for older adults. 

PMID- 23972542
TI  - Short-term changes in sleep, mastery & stress: impacts on depression and health
      in dementia caregivers.
AB  - Dementia caregiving is stressful and can result in negative health outcomes.
      Understanding the intermediate dynamic changes in caregiving may help nurses
      target interventions. The purposes of this study were to measure short-term
      changes in sleep, mastery, and stress in dementia caregivers and to explore their
      impacts on caregiver depression and health. Seventy-four caregivers were measured
      at baseline, 4, and 8 weeks for changes in global mastery, caregiver mastery,
      sleep quality, perceived stress, depression, and health. Over the 8 weeks,
      changes were observed in sleep, mastery, stress, and health measures, indicating
      support for the dynamic and complex nature of dementia caregiving. Sleep and
      perceived stress made unique contributions to depression, but the contributions
      to health varied. Clinical implications for nurses are to assess caregivers
      frequently and reinforce successful interventions periodically as caregiving
      evolves. 

PMID- 23972543
TI  - Assisting for 'better' diabetes management.

PMID- 23972544
TI  - Courtesy in caring.

PMID- 23972546
TI  - Thorax Innovation (TORINO).

PMID- 23972545
TI  - Cytokines from the tumor microenvironment modulate sirtinol cytotoxicity in A549
      lung carcinoma cells.
AB  - Cytokines in tumor microenvironment play an important role in the success or
      failure of molecular targeted therapies. We have chosen tumor necrosis factor
      alpha (TNF-alpha), TNF related apoptosis inducing ligand (TRAIL), insulin-like
      growth factor 1 (IGF-1) and transforming growth factor beta (TGF-beta) as
      representative pro-inflammatory, pro-apoptotic, anti-apoptotic and anti
      inflammatory tumor derived cytokines. Analysis of Oncomine database revealed the
      differential expression of these cytokines in a subset of cancer patients. The
      effects of these cytokines on cytotoxicity of FDA approved drugs - cisplatin and
      taxol and inhibitors of epidermal growth factor receptor - AG658, Janus kinase -
      AG490 and SIRT1 - sirtinol were assessed in A549 lung cancer cells. TRAIL
      augmented cytotoxicity of sirtinol and IGF-1 had a sparing effect. Since TRAIL
      and IGF-1 differentially modulated sirtinol cytotoxicity, further studies were
      carried out to identify the mechanisms. Sirtinol or knockdown of SIRT1 increased
      the expression of death receptors DR4 and DR5 and sensitized A549 cells to TRAIL.
      Increased cell death in presence of TRAIL and sirtinol was caspase independent
      and demonstrated classical features of necroptosis. Inhibition of iNOS increased
      caspase activity and switched the mode of cell death to caspase mediated
      apoptosis. Interestingly, sirtinol or SIRT1 knockdown did not increase IGF-1R
      expression. Instead, it abrogated ligand induced downregulation of IGF-1R and
      increased cell survival through PI3K-AKT pathway. In conclusion, these findings
      reveal that the tumor microenvironment contributes to modulation of cytotoxicity
      of drugs and that combination therapy, with agents that increase TRAIL signaling
      and suppress IGF-1 pathway may potentiate anticancer effect.

PMID- 23972547
TI  - Drugs induced pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a rare disorder characterized by
      progressive obliteration of the pulmonary microvasculature, resulting in elevated
      pulmonary vascular resistance and premature death. According to the current
      classification, PAH can be associated with exposure to certain drugs or toxins,
      particularly appetite suppressant drugs, such as aminorex, fenfluramine
      derivatives and benfluorex. These drugs have been confirmed to be risk factors
      for PAH and were withdrawn from the market. The supposed mechanism is an increase
      in serotonin levels, which was demonstrated to act as a growth factor for the
      pulmonary arterial smooth muscle cells. Amphetamines, phentermine and mazindol
      were less frequently used but are also considered as possible risk factors for
      PAH. Dasatinib, a dual Src/Abl kinase inhibitor, used in the treatment of chronic
      myelogenous leukaemia was associated with cases of severe PAH, in part reversible
      after its withdrawal. Recently several studies raised the potential endothelial
      dysfunction that could be induced by interferon, and few cases of PAH have been
      reported with interferon therapy. Other possible risk factors for PAH include:
      nasal decongestants, like phenylpropanolamine, dietary supplement - L-Tryptophan,
      selective serotonin reuptake inhibitors, pergolide and other drugs that could act
      on 5HT2B receptors. Interestingly, PAH remains a rare complication of these
      drugs, suggesting possible individual susceptibility and further studies are
      needed to identify patients at risk of drugs induced PAH.

PMID- 23972548
TI  - [Increase of health scare in the media: what relevance?].

PMID- 23972549
TI  - [Antithrombotic treatment and cancer].
AB  - Five to 10 % of cancers are complicated by venous thromboembolism. A score is
      available to classify patients according to their risk of venous thromboembolism.
      The long-term prophylaxis is not recommended in patients with cancer, even if it
      reduces the incidence of thromboembolic events, due to the high number of
      patients to treat to prevent one event. The treatment of venous thromboembolism
      in cancer is based on the use of low-molecular weight heparin for at least 3
      months. The potential role of antithrombotic drugs in the prevention and adjuvant
      treatment of some cancers is being evaluated.

PMID- 23972550
TI  - [Antithrombotic medication: Which modifications with the new oral
      anticoagulants?].

PMID- 23972551
TI  - Complications of chemotherapy, a basic science update.
AB  - Anthracyclines, discovered 50 years ago, are antibiotics widely used as
      antineoplastic agents and are among the most successful anticancer therapies ever
      developed to treat a wide range of cancers, including hematological malignancies,
      soft tissue sarcomas and solid tumors. However, some anthracyclines, including
      doxorubicin, exhibit major signs of cardiotoxicity that may ultimately lead to
      heart failure (HF). Despite intensive research on doxorubicine-induced
      cardiotoxicity, the underlying mechanisms responsible for doxorubicin-induced
      cardiotoxicity have not been fully elucidated yet. Published literature so far
      has focused mostly on mitochondria dysfunction with consequent oxidative stress,
      Ca(2+) overload, and cardiomyocyte death as doxorubicin side effects, leading to
      heart dysfunction. This review focuses on the current understanding of the
      molecular mechanisms underlying doxorubicin-induced cardiomyocyte death (i.e.:
      cardiomyocyte death, mitochondria metabolism and bioenergetic alteration), but we
      will also point to new directions of possible mechanisms, suggesting potent prior
      or concomitant alterations of specific signaling pathways with molecular actors
      directly targeted by the anticancer drugs itself (i.e. calcium homeostasis or
      cAMP signaling cascade). The mechanisms of anticancer cardiac toxicity may be
      more complex than just mitochondria dysfunction. Partnership of both basic and
      clinical research is needed to promote new strategies in diagnosis, therapies
      with concomitant cardioprotection in order to achieve cancer treatment with
      acceptable cardiotoxicity along life span.

PMID- 23972552
TI  - [Food poisonings related to organic buckwheat contaminated with Datura sp.: a
      poison control and toxicovigilance center activity].

PMID- 23972553
TI  - Inotropic agents in apical ballooning syndrome: a therapeutical dilemma.

PMID- 23972554
TI  - Arrhythmias in patients with acute coronary syndrome in the first 24 hours of
      hospitalization.
AB  - OBJECTIVES: In patients with acute coronary syndrome (ACS), we sought to: 1)
      describe arrhythmias during hospitalization, 2) explore the association between
      arrhythmias and patient outcomes, and 3) explore predictors of the occurrence of
      arrhythmias. METHODS: In a prospective sub-study of the IMMEDIATE AIM study, we
      analyzed electrocardiographic (ECG) data from 278 patients with ACS. On emergency
      department admission, a Holter recorder was attached for continuous 12-lead ECG
      monitoring. RESULTS: Approximately 22% of patients had more than 50 premature
      ventricular contractions (PVCs) per hour. Non-sustained ventricular tachycardia
      (VT) occurred in 15% of patients. Very few patients (<= 1%) had a malignant
      arrhythmia (sustained VT, asystole, torsade de pointes, or ventricular
      fibrillation). Only more than 50 PVCs/hour independently predicted an increased
      length of stay (p < .0001). No arrhythmias predicted mortality. Age greater than
      65 years and a final diagnosis of acute myocardial infarction independently
      predicted more than 50 PVCs per hour (p = .0004). CONCLUSIONS: Patients with ACS
      seem to have fewer serious arrhythmias today, which may have implications for the
      appropriate use of continuous ECG monitoring.

PMID- 23972555
TI  - The seven Cs of the high acceptability of home-based VCT: results from a mixed
      methods approach in Zambia.
AB  - HIV testing and counselling is a critical gateway to prevention and treatment.
      Yet, coverage remains insufficient, few couples are tested together and gender
      differences in access exist. We used an embedded mixed methods approach to
      investigate possible explanations for the high acceptance of home-based voluntary
      HIV counselling and testing (HB-VCT) in a pair-matched cluster-randomized trial
      in Zambia. A baseline survey included 1694 individuals in 36 clusters. Adults in
      18 intervention clusters were offered HB-VCT by lay counsellors. Standard testing
      services were available in both trial arms. After the completion of the
      intervention, a follow-up survey was conducted in all trial clusters. In
      addition, 21 in-depth interviews and one focus group discussion were conducted
      with home-based VCT clients in the intervention arm. Informants favoured the
      convenience, confidentiality and credibility of HB-VCT. Counsellors were
      perceived as trustworthy owing to their closeness and conduct, and the consent
      process was experienced as convincing. Couple testing was selected by 70% of
      cohabiting couples and was experienced as beneficial by both genders. Levels of
      first-time testing (68% vs. 29%, p < 0.0001) and re-testing (94% vs. 74%, p <
      0.0001) were higher in the intervention than in the control arm. Acceptance of
      HIV testing and counselling is dependent on stigma, trust and gender. The
      confidentiality of home-based VCT was essential for overcoming stigma-related
      barriers, and the selection of local counsellors was important to ensure trust in
      the services. The high level of couple counselling within HB-VCT may contribute
      to closing the gender gap in HIV testing, and has benefits for both genders and
      potentially for prevention of HIV transmission. The study demonstrates the
      feasibility of achieving high test coverage with an opt-in consent approach. The
      embedded qualitative component confirmed the high satisfaction with HB-VCT
      reported in the quantitative survey and was crucial to fully understand the
      intervention and its consequences.

PMID- 23972556
TI  - Semantic conditioning of salivary pH for communication.
AB  - OBJECTIVES: Semantic conditioning of salivary pH was investigated as a new
      paradigm for binary communication. METHODS AND MATERIALS: In a sample of eleven
      healthy participants, affirmation or negation of presented statements were paired
      with milk and lemon to condition changes in salivary pH level. RESULTS:
      Significant differences between the conditioned reactions were found at the group
      level. However, the analysis of pH changes on single-subject level revealed
      significant differences between affirmative and negative responses to the
      presented statements only for isolated samples in few participants. When
      classifying a change in pH value of more than .01 as correct response to a
      statement, only responses to affirmative statements reached mean accuracies of
      more than 60%. CONCLUSION: Improvements in the paradigm are necessary before
      testing it with the critical target population of patients to prove its profit
      for basic yes/no communication in case no other reliable means of communication
      could be preserved.

PMID- 23972557
TI  - Unusual costochondral bone graft complication.
AB  - In hemifacial microsomia, patients with severely hypoplastic mandibles (Pruzansky
      type III) require replacement of the ramus and condyle unit. Common complications
      of this procedure include graft fracture and overgrowth of the graft. An uncommon
      case of osteolysis of the costochondral graft with osteitis of the middle cranial
      fossa is reported herein. To our knowledge, no such case has been reported in the
      literature previously. The aim of this report is to present the only known case
      and to discuss the contributing factors. 

PMID- 23972558
TI  - The osteogenic activity of human mandibular fracture haematoma-derived cells is
      stimulated by low-intensity pulsed ultrasound in vitro.
AB  - Low intensity pulsed ultrasound (LIPUS) stimulation is a clinically established
      treatment method used to accelerate long bone fracture healing; however, this
      method is currently not applied to mandibular fractures. In this study, we
      investigated the effects of LIPUS on human mandibular fracture haematoma-derived
      cells (MHCs) in order to explore the possibility of applying LIPUS treatment to
      mandibular fractures. MHCs were isolated from five patients. The cells were
      divided into two groups: (1) LIPUS (+) group: MHCs cultured in osteogenic medium
      with LIPUS treatment; and (2) LIPUS (-) group: MHCs cultured in osteogenic medium
      without LIPUS treatment. The osteogenic differentiation potential and
      proliferation of the MHCs were compared between the two groups. The waveform used
      was equal to the wave conditions of a clinical fracture healing system. The gene
      expression levels of ALP, OC, Runx2, OSX, OPN, and PTH-R1 and mineralization were
      increased in the LIPUS (+) group compared to the LIPUS (-) group. There were no
      significant differences in cell proliferation between the two groups. These
      findings demonstrate the significant effects of LIPUS on the osteogenic
      differentiation of MHCs. This study provides significant evidence for the
      potential usefulness of the clinical application of LIPUS to accelerate
      mandibular fracture healing. 

PMID- 23972559
TI  - Cigarette smoking and associated risk of multiple sclerosis in the Iranian
      population.
AB  - Exposure to cigarette smoke is emerging as an environmental risk factor for
      multiple sclerosis (MS). We investigated the possible association between
      environmental tobacco smoke, its cumulative exposure, and MS risk. We used data
      from the Iranian Multiple Sclerosis Registry to identify a case-control of 662
      patients who had MS and a comparison group of 394 patients. Information regarding
      current smoking status, including the number of cigarettes smoked per day,
      duration, and smoking pack-years indicative of cumulative dose of tobacco smoked
      was obtained. We analyzed the incidence of MS among ever-smokers who had been
      smokers during their disease course and prior to disease onset in comparison with
      never-smokers who had never been exposed by calculating the odds ratio (OR) with
      a 95% confidence interval (CI) employing logistic regression. Of the 662 MS
      patients, there were 523 women (79.0%) and 139 men (21.0%), with a mean age of 31
      +/- 10.0 years at disease onset. The risk for MS was increased among ever-smokers
      (OR = 1.78, 95% CI = 1.22-2.59, p = 0.03) compared to never-smokers. As compared
      with never smokers, the OR for patients with 6-10 pack years was 2.91 for men
      (95% CI = 1.11-9.47, p = 0.03) and 1.69 for women (95% CI = 1.02-6.45, p = 0.04).
      Our results demonstrate that cigarette smoking is significantly associated with
      an increased risk for MS. The risk effects of smoking were more noticeable in
      male patients and at higher tobacco doses.

PMID- 23972560
TI  - Endovascular treatment of carotid cavernous aneurysms: complications, outcomes
      and comparison of interventional strategies.
AB  - The best treatment modality for cavernous carotid aneurysms (CCA) remains
      unclear. We treated 82 CCA in 79 patients with endovascular coiling (n=14), stent
      assistance (n=53), and carotid vessel deconstruction (CVD) (n=15). Favorable
      outcomes were defined as a Glasgow Outcome Scale of 4 to 5 without worsening
      signs or symptoms. Mean CCA size was 13.3+/-9.2 mm, and CCA treated with CVD were
      larger (p=0.010). Fourteen patients had incidental CCA, 40 (50.6%) had cranial
      nerve palsies (CNP), and 25 (31.7%) had pain leading to diagnosis. Immediate
      occlusion (>95%) occurred in 91.5% of aneurysms. Ischemic or hemorrhagic
      complications developed following eight treatments (9.8%) and three were
      permanent (3.7%). There were no deaths, and favorable discharge outcome occurred
      following 87.8% of procedures. Although there was no difference in immediate
      occlusion or complications amongst treatment cohorts, fewer permanent
      complications (0% versus 10.3%, p=0.041) and favorable discharge outcomes
      (p=0.039) were associated with stent assisted treatment. Follow-up was available
      following 75 procedures (mean 21.4+/-17.4 months). Recanalization occurred in 36%
      of patients and retreatment in 25%. Patients presenting with CNP improved over
      time (p<0.001); 54% of patients presenting with CNP remained unchanged while 46%
      improved; there was no difference in improvement rates stratified by treatment.
      Favorable follow-up outcome occurred after 96% of treatments and those receiving
      stents were more likely to have favorable outcome in multivariate analysis
      (p=0.039). Endovascular therapy is a safe and effective therapy for CCA. When
      possible, stent assisted therapy may be the best option with fewer complications
      and low recanalization rates.

PMID- 23972561
TI  - Spontaneous vertebral arteriovenous fistula causing cervical myelopathy and acute
      ischemic strokes treated by endovascular balloon-assisted coiling and Onyx
      embolization.
AB  - Vertebral arteriovenous fistulas (VAVF) are infrequent lesions characterized by
      abnormal communication of the extracranial vertebral artery or one of its
      branches to the surrounding venous plexuses, without the presence of any
      intervening vessels. We describe a rare occurrence of a patient with VAVF
      presenting with acute ischemic stroke, encephalomalacia from multiple prior
      embolic events, and cervical myelopathy, which was successfully treated by coil
      assisted Onyx embolization (ev3 Endovascular, Plymouth, MN, USA) with balloon for
      flow arrest. Our patient demonstrates that point occlusion with embolization for
      VAVF can be a feasible, safe, and effective treatment option for complete
      obliteration of the fistula, with subsequent reduction in the volume of the intra
      spinal canal venous plexus. Although it is postulated that thromboembolism is
      less common because of redirection of flow to the venous side of the fistula, our
      patient also illustrates the potential for to-fro flow in such a fistula to
      result in embolic injury to the distal circulation. 

PMID- 23972562
TI  - The applause sign in Parkinson's disease patients is related to dysexecutive
      syndrome.
AB  - Recent publications report that a positive applause sign is not only present in
      patients with neurodegenerative diseases where the subcortical structures are
      affected but also in patients with cortical dementia. The nature of this sign
      remains unknown. This study aimed to determine the frequency of the applause sign
      and its correlation with cognitive impairment in patients with idiopathic
      Parkinson's disease. The study included 30 non-depressed patients diagnosed with
      idiopathic Parkinson's disease. Study patients underwent the Unified Parkinson
      Disease Rating Scale part III, Dementia Rating Scale (DRS), Raven's Colored
      Progressive Matrices, and Mill Hill Vocabulary tests. Statistical analysis was
      performed by use of the parametric Student's t-test, nonparametric Mann-Whitney U
      test and Fisher's exact test, with the level of significance set at p<0.05.
      Negative applause sign was recorded in 66.7% and positive applause sign in 33.3%
      of patients. There were no between-group differences according to age, disease
      duration, or severity of motor symptoms. The positive applause sign group had
      significantly lower scores on the initiation/perseveration subscale of the DRS
      and a significantly higher frequency of scores below the cut-off score on the
      conceptualization and construction subscales of the DRS. The applause sign
      appears to be part of a broader dysexecutive syndrome in idiopathic Parkinson's
      disease. 

PMID- 23972563
TI  - Long thoracic nerve release for scapular winging: clinical study of a continuous
      series of eight patients.
AB  - Scapular winging secondary to serratus anterior muscle palsy is a rare pathology.
      It is usually due to a lesion in the thoracic part of the long thoracic nerve
      following violent upper-limb stretching with compression on the nerve by the
      anterior branch of thoracodorsal artery at the "crow's foot landmark" where the
      artery crosses in front of the nerve. Scapular winging causes upper-limb pain,
      fatigability or impotence. Diagnosis is clinical and management initially
      conservative. When functional treatment by physiotherapy fails to bring recovery
      within 6 months and electromyography (EMG) shows increased distal latencies,
      neurolysis may be suggested. Muscle transfer and scapula-thoracic arthrodesis are
      considered as palliative treatments. We report a single-surgeon experience of
      nine open neurolyses of the thoracic part of the long thoracic nerve in eight
      patients. At 6 months' follow-up, no patients showed continuing signs of winged
      scapula. Control EMG showed significant reduction in distal latency; Constant
      scores showed improvement, and VAS-assessed pain was considerably reduced.
      Neurolysis would thus seem to be the first-line surgical attitude of choice in
      case of compression confirmed on EMG. The present results would need to be
      confirmed in larger studies with longer follow-up, but this is made difficult by
      the rarity of this pathology. LEVEL OF EVIDENCE: III.

PMID- 23972564
TI  - Indentation response of human patella with elastic modulus correlation to
      localized fractal dimension and bone mineral density.
AB  - The goal of this study was to determine material properties for the anterior
      cortex and subcortical regions of human patellae and relate those properties to
      mineral density and fractal dimension of the bone. Ten human patellae were
      obtained from eight fresh frozen human cadavers and subjected to anteriorly
      directed spherical indentation-relaxation experiments using two different sized
      indenters to two different indentation depths. Response data were fit to a three
      mode viscoelastic model obtained through elastic-viscoelastic correspondence of
      the Hertzian contact relation for spherical indentation. A location-specific
      effective bone density measurement that more heavily weighted bone material close
      to the indentation site (by von Mises stress distribution) was determined from
      micro-computed tomography (38um resolution) data captured for each specimen. The
      same imagery data were used to compute location specific fractal dimension
      estimates for each indentation site. Individual and averaged patella material
      models verified the hypothesis that when the larger indenter and greater
      indentation depth is used to engage the surface and deeper (trabecular) bone, the
      bone exhibits a more compliant response than when only the surface (cortical)
      bone was engaged (instantaneous elastic modulus was 325MPa vs. 207MPa, p<0.05).
      Effective bone mineral density was shown to be a significant predictor of the
      elastic modulus for both small and large indentation types (p<0.05) despite
      relatively low correlations. Exponential regressions of fractal dimension on
      elastic modulus showed significant relationships with high correlation for both
      the small (R(2)=0.93) and large (R(2)=0.97) indentations. 

PMID- 23972565
TI  - Minimally invasive total knee arthroplasty; a pragmatic randomised controlled
      trial reporting outcomes up to 2 year follow up.
AB  - BACKGROUND: We present a prospective, randomised, multi-surgeon, controlled trial
      comparing minimally invasive (MIS) and standard approach total knee arthroplasty
      (TKA). METHODS: Participants underwent unilateral TKA. Patients were randomised
      to Bristol, quadriceps sparing MIS or standard medial parapatellar approaches.
      Length of stay with secondary outcome measures including knee range of movement,
      Oxford Knee Score (OKS), Western Ontario and McMaster Universities Arthritis
      Index (WOMAC) and American Knee Society Score (KSS) up to 2 years. Radiographic
      and post operative assessment was blinded. RESULTS: 86 patients (92 knees)
      participated in the study. Mean operative time between MIS and control groups was
      95.5 (95% CI 90.0-101.0) and 94.8 (95% CI 88.2-101.4) minutes respectively. Mean
      readiness for discharge was shorter in the MIS group 4.5+/-1.5 (95% CI, 4.1-4.9)
      days versus 5.9+/-2.7 (95% CI, 5.1-6.7) days amongst controls (p=0.004). Patients
      in the MIS group had fewer complications (p=0.003). One patient developed a deep
      vein thrombosis (DVT) and one required revision surgery, both in the control
      group. 83 patients completed follow up to 2 years (40 MIS, 43 controls). Range of
      movement and other outcome measures improved up to 1 year post-operatively with
      no statistically significant differences between MIS and controls. We found no
      evidence of radiographic loosening in either group at the 2 year follow up.
      CONCLUSIONS: MIS offers reduced length of stay and fewer complications for
      patients following TKR without evidence of component mal-alignment. Our findings
      of fewer systemic complications in MIS TKR patients warrant further future study.
      LEVEL OF EVIDENCE: Level 1.

PMID- 23972566
TI  - Mid-term results of transphyseal anterior cruciate ligament reconstruction in
      children and adolescents.
AB  - BACKGROUND: Optimal therapy for anterior cruciate ligament (ACL) rupture in the
      paediatric population still provokes controversy. Although conservative and
      operative treatments are both applied, operative therapy is slightly favored.
      Among available surgical techniques are physeal-sparing reconstruction and
      transphyseal graft fixation. The aim of this study was to present our mid-term
      results after transphyseal ACL reconstruction. METHODS: Fifteen young patients
      (mean age=12.8+/-2.6, range=6.2-15.8 years, Tanner stage=2-4) with open physis
      and traumatic anterior cruciate rupture who had undergone transphyseal ACL
      reconstruction with unilateral quadriceps tendon graft were prospectively
      analyzed. All children were submitted to radiological evaluation to determine the
      presence of clearly open growth plates in both the distal femur and proximal
      tibia. Postoperatively, all patients were treated according to a standardized
      rehabilitation protocol and evaluated by radiographic analysis and the Lysholm
      Gillquist and IKDC 2000 scores. Their health-related quality of life was measured
      using the SF-12 PCS (physical component summary) and MCS (mental component
      summary) questionnaires. RESULTS: Mean postoperative follow-up was 4.1 years.
      Mean Lysholm-Gillquist score was 94.0. Thirteen of the 15 knees were considered
      nearly normal on the IKDC 2000 score. The mean SF-12 questionnaire score was
      54.0+/-4.8 for SF-12 PCS and 59.1+/-3.7 for SF-12 MCS. No reruptures were
      observed. Radiological analysis detected one knee with valgus deformity. All
      patients had a normal gait pattern without restrictions. CONCLUSION: Transphyseal
      reconstruction of the anterior cruciate ligament shows satisfactory mid-term
      results in the immature patient.

PMID- 23972567
TI  - Molluscum contagiosum virus infection.
AB  - Molluscum contagiosum virus is an important human skin pathogen: it can cause
      disfigurement and suffering in children, in adults it is less common and often
      sexually transmitted. Extensive and persistent skin infection with the virus can
      indicate underlying immunodeficiency. Traditional ablative therapies have not
      been compared directly with newer immune-modulating and specific antiviral
      therapies. Advances in research raise the prospect of new approaches to treatment
      informed by the biology of the virus; in human skin, the infection is localised
      in the epidermal layers, where it induces a typical, complex hyperproliferative
      lesion with an abundance of virus particles but a conspicuous absence of immune
      effectors. Functional studies of the viral genome have revealed effects on
      cellular pathways involved in the cell cycle, innate immunity, inflammation, and
      cell death. Extensive lesions caused by molluscum contagiosum can occur in
      patients with DOCK8 deficiency-a genetic disorder affecting migration of
      dendritic and specialised T cells in skin. Sudden disappearance of lesions is the
      consequence of a vigorous immune response in healthy people. Further study of the
      unique features of infection with molluscum contagiosum virus could give
      fundamental insight into the nature of skin immunity. 

PMID- 23972568
TI  - [Pain and inflammation of the pinna].

PMID- 23972569
TI  - Nonlinear Kalman Filtering for acoustic emission source localization in
      anisotropic panels.
AB  - Nonlinear Kalman Filtering is an established field in applied probability and
      control systems, which plays an important role in many practical applications
      from target tracking to weather and climate prediction. However, its application
      for acoustic emission (AE) source localization has been very limited. In this
      paper, two well-known nonlinear Kalman Filtering algorithms are presented to
      estimate the location of AE sources in anisotropic panels: the Extended Kalman
      Filter (EKF) and Unscented Kalman Filter (UKF). These algorithms are applied to
      two cases: velocity profile known (CASE I) and velocity profile unknown (CASE
      II). The algorithms are compared with a more traditional nonlinear least squares
      method. Experimental tests are carried out on a carbon-fiber reinforced polymer
      (CFRP) composite panel instrumented with a sparse array of piezoelectric
      transducers to validate the proposed approaches. AE sources are simulated using
      an instrumented miniature impulse hammer. In order to evaluate the performance of
      the algorithms, two metrics are used: (1) accuracy of the AE source localization
      and (2) computational cost. Furthermore, it is shown that both EKF and UKF can
      provide a confidence interval of the estimated AE source location and can account
      for uncertainty in time of flight measurements. 

PMID- 23972570
TI  - Timing of sentinel lymph node biopsy in breast cancer patients receiving
      neoadjuvant chemotherapy.

PMID- 23972571
TI  - Unexpected rectal cancer after TEM: outcome of completion surgery compared with
      primary TME.
AB  - BACKGROUND: Transanal endoscopic microsurgery (TEM) has gained wide-spread
      acceptance as a safe and useful technique for the resection of rectal adenomas
      and selected T1 malignant lesions. If the lesion appears >T1 rectal cancer after
      resection with TEM, a completion TME resection is recommended. The aim of this
      study was to investigate the results of TME surgery after TEM for rectal cancer.
      METHODS: In four tertiary referral hospitals for TEM, all patients with
      completion TME surgery after initial TEM were selected. All eligible patients who
      were treated with 5 * 5 Gy radiotherapy followed by TME surgery from the Dutch
      TME trial were selected as reference group. A multivariate logistic regression
      model was used to calculate odds ratio's (OR) for colostomies and for colo- and
      ileostomies combined. Local recurrence and survival rates were compared in hazard
      ratio's (HR) using the multivariate Cox proportional hazard model. RESULTS: Fifty
      nine patients were included in the TEM-COMPLETION group and 881 patients from the
      TME trial. In the TEM-COMPLETION group, 50.8% of the patients had a colostomy
      compared to 45.9% in the TME trial, OR 2.51 (p < 0.006). There is no significant
      difference when ileo- and colostomies are analyzed together. In the TEM
      COMPLETION group, 10.2% developed a local recurrence compared to 5.2% in the TME
      trial, HR 6.8 (p < 0.0001). CONCLUSIONS: Completion TME surgery after TEM for
      unexpected rectal adenocarcinoma results in more colostomies and higher local
      recurrence rates compared to one stage TME surgery preceded with preoperative 5 *
      5 Gy radiotherapy. Pre-operative investigations must be optimized to distinguish
      malignant and benign lesions and prevent avoidable local recurrence and
      colostomies.

PMID- 23972573
TI  - Pediatric palliative care in sub-saharan Africa: a systematic review of the
      evidence for care models, interventions, and outcomes.
AB  - CONTEXT: The progressive disease burden among children in sub-Saharan Africa
      means the provision of palliative care is essential and should be provided
      alongside treatment where it is available. OBJECTIVES: To systematically review
      the evidence for pediatric palliative care models, interventions, and outcomes to
      appraise the state of the science and inform best practice. METHODS: A systematic
      review search strategy was implemented in eight electronic databases, the search
      results reported using a PRISMA statement, and findings tabulated. RESULTS: In
      terms of evidence of palliative care provision and outcomes, only five articles
      were identified. These represent a small range of acute, community, and hospice
      care and offer some limited guidance on the development and delivery of services.
      CONCLUSION: Pediatric palliative care is a pressing clinical and public health
      challenge in sub-Saharan Africa. Explicit evidence-based models of service
      development, patient assessment, and evidence for control of prevalent problems
      (physical, psychological, social, spiritual, and developmental) are urgently
      needed. Greater research activity is urgently required to ensure an evidence
      based response to the enormous need for pediatric palliative care in sub-Saharan
      Africa.

PMID- 23972574
TI  - A novel website to prepare diverse older adults for decision making and advance
      care planning: a pilot study.
AB  - CONTEXT: We have reconceptualized advance care planning (ACP) as a multistep
      process focused on preparing patients with skills needed for communication and in
      the-moment decision making. OBJECTIVES: To operationalize this paradigm, we
      created an easy-to-use ACP website (prepareforyourcare.org) based on a
      theoretical framework of behavior change and pilot-tested its efficacy to engage
      older adults in ACP. METHODS: At baseline and 1 week after viewing the PREPARE
      website, we assessed behavior change in ACP by using a validated survey that
      includes Process Measures (knowledge, contemplation, self-efficacy, and
      readiness, 5-point Likert scales) and Action Measures (yes/no whether an ACP
      behavior was completed). We also assigned participants into behavior change
      stages (i.e., precontemplation, contemplation, preparation, action, maintenance)
      and determined the percentage of participants who moved from precontemplation at
      baseline to higher stages at 1 week. We also assessed PREPARE ease-of-use (10
      point scale, 10 being the easiest). Changes were assessed with Wilcoxon signed
      rank sum tests and McNemar's tests. RESULTS: Mean age of the participants was
      68.4 years (SD 6.6), and 65% were nonwhite. Behavior Change Process Measures
      average Likert scores increased from 3.1 (0.9) to 3.7 (0.7), P < 0.001. Action
      Measures did not change significantly. However, precontemplation significantly
      decreased for most actions (e.g., talking to doctor about desired medical care,
      61% to 35%, P < 0.003), with a mean decrease of 21% (range, 16%-33%). PREPARE was
      rated a nine of ten (+/-1.9) for ease-of-use. CONCLUSION: A new, patient-centered
      ACP website that focuses on preparing patients for communication and decision
      making significantly improves engagement in the process of ACP and behavior
      change. A clinical trial of PREPARE is currently underway.

PMID- 23972576
TI  - Dosing and antipyretic efficacy of oral acetaminophen in children.
AB  - BACKGROUND: A standardized approach to dosing acetaminophen in pediatric
      populations was published in 1983. That review proposed specific weight-related
      dosing for infants and children weighing 6 through 95 lb and an age-based
      schedule for children aged <4 months through 11 years. Subsequent clinical
      studies evaluating these and alternative doses of acetaminophen supported the
      recommended 10-15-mg/kg dose. OBJECTIVE: This article reviewed published and
      unpublished pediatric antipyretic data to provide a critical assessment of the 10
      15-mg/kg oral dose and the current pediatric oral dosing schedules for
      acetaminophen. METHODS: Published literature and unpublished clinical trials that
      evaluated the antipyretic efficacy of acetaminophen in children were reviewed.
      The PubMed database was searched using the term acetaminophen or paracetamol,
      with study criteria limited to randomized, controlled trials; oral dosing;
      patient age <12 years; and publication between 1982 and August 2012. All of the
      sponsor's unpublished antipyretic clinical studies completed between 1980 and
      August 2012 and involving at least 1 oral-formulation acetaminophen-only
      treatment arm were identified. Data from published literature containing
      sufficient detail to verify doses; dosing frequency; and, when necessary,
      estimates from figures, and from acetaminophen arms of the unpublished studies
      were analyzed. RESULTS: Thirteen unpublished trials enrolled 705 children to
      receive an oral dose of 10-15 mg/kg of acetaminophen. This dose resulted in a
      rapid onset of temperature reduction, with a maximum temperature decrement of ~3
      hours following administration. Results from 40 published clinical trials in
      which 2332 children received oral acetaminophen for fever support these findings.
      The most common adverse events reported in any of the reported studies were
      gastrointestinal in nature and generally mild in intensity. CONCLUSIONS: Data
      support the recommended 10-15-mg/kg oral dose and demonstrate that the age and
      weight schedules for over-the-counter acetaminophen proposed in 1983 remain
      appropriate.

PMID- 23972575
TI  - Assessment of reasons for referral and activities of hospital palliative care
      teams using a standard format: a multicenter 1000 case description.
AB  - CONTEXT: The many benefits of hospital palliative care teams (PCTs) are well
      known. However, their specific activities have not been fully clarified, and no
      standardized methods for reporting PCT activities are available. OBJECTIVES: The
      aim of this study was to investigate, through the use of a standard format, the
      activities performed by hospital PCTs in Japan. METHODS: This was a prospective
      observational study. A total of 21 hospital PCTs were included in this study, and
      each recruited approximately 50 consecutively referred patients. Participating
      PCTs filled in a standard form for reporting activities. RESULTS: We obtained
      data from 1055 patients who were referred to PCTs. Of the 1055 patients, 1005
      patients (95%) had cancer. The median number of reasons for referral and problems
      identified by PCTs was two (0-22) and four (0-18), respectively. The two major
      reasons for referral were pain (63%) and anxiety/depression/grief/emotional
      burden (22%). The major recommendations were pharmacological treatment (74%),
      care for the patient's physical symptoms (49%), and support for patient's
      decision making (38%). The major activities performed by the PCTs were
      comprehensive assessment (90%), care for the patient's physical symptoms (77%),
      and pharmacological treatment (74%). CONCLUSION: The components of hospital PCT
      activities were successfully measured using the Standard Format for Reporting
      Hospital PCT Activity. The results of this study and the format for reporting
      hospital PCT activity could be effective in improving hospital PCT practice and
      for the education of new hospital PCT members.

PMID- 23972577
TI  - Efficacy and speed of onset of pain relief of fast-dissolving paracetamol on
      postsurgical dental pain: two randomized, single-dose, double-blind, placebo
      controlled clinical studies.
AB  - BACKGROUND: Paracetamol (APAP), also known as acetaminophen, is the most commonly
      used over-the-counter analgesic for the treatment of mild-to-moderate pain.
      However, the speed of onset of pain relief is limited mainly to the standard,
      immediate-release formulation. Efficacy and speed of onset of pain relief are
      critical in acute pain situations such as postsurgical dental pain, because
      reducing pain can improve clinical outcome and reduce the risk of transition from
      acute pain to more chronic pain. Efficacy and rapid onset also reduce the risk of
      excessive dosing with the analgesic. OBJECTIVE: We sought to investigate the dose
      response efficacy and speed of onset of pain relief of a fast-dissolving APAP
      formulation compared with lower doses of APAP and placebo in dental patients
      after impacted third molar extraction. METHODS: Two single-center, single-dose,
      randomized, placebo-controlled, double-blind, double-dummy, parallel-group
      studies (Study I and Study II) were conducted to evaluate the efficacy and speed
      of onset of pain relief of different doses of a fast-dissolving APAP tablet (FD
      APAP), standard APAP, and placebo in patients with postsurgical dental pain
      following third molar extraction. In Study I, a single dose of FD-APAP 1000 mg,
      FD-APAP 500 mg, or placebo was given to 300 patients; in Study II, a single dose
      of FD-APAP 1000 mg, standard APAP 650 mg, or placebo was given to 401 patients.
      All 701 patients from both studies were included in the analysis and safety
      assessment. RESULTS: FD-APAP 1000 mg demonstrated significantly greater effect
      compared with FD-APAP 500 mg, APAP 650 mg, and placebo for all efficacy
      measurements, including sum of pain relief and pain intensity difference, total
      pain relief, sum of pain intensity difference, pain intensity difference, and
      pain relief score during 6 hours after the dose. Onset of confirmed first
      perceptible relief in subjects treated with FD-APAP 1000 mg was 15 minutes, which
      was 32% and 25% significantly shorter than onset of pain relief of FD-APAP 500 mg
      (22 minutes) and standard APAP 650 mg (20 minutes), respectively. FD-APAP 500 mg
      and APAP 650 mg demonstrated efficacy over placebo for most of the measurements;
      however, their effects were significantly lower and lasted for a shorter period
      of time than for FD-APAP 1000 mg. All study treatments were well tolerated.
      CONCLUSIONS: FD-APAP 1000 mg tablets demonstrated efficacy over placebo. Also, FD
      APAP 1000 mg had significantly superior effect, faster onset, and longer duration
      of pain relief compared with FD-APAP 500 mg and APAP 650 mg tablets.

PMID- 23972578
TI  - Evolving concepts: the negative effect of minimal hepatic encephalopathy and role
      for prophylaxis in patients with cirrhosis.
AB  - BACKGROUND: Hepatic encephalopathy (HE), which may be categorized as minimal or
      overt, is a serious and progressive neuropsychiatric condition that occurs in
      patients with liver disease or portosystemic shunting. Overt HE (OHE) presents as
      a wide spectrum of clinical signs and symptoms, ranging in severity from mild
      confusion to life-threatening coma. Minimal HE (MHE) is a more subtle form of the
      condition; it is characterized by deficits in cognitive function in patients with
      a normal clinical examination. OBJECTIVE: The purpose was to review the effect of
      MHE on patients and caregivers, as well as its currently available diagnostic and
      treatment options. METHODS: A MEDLINE search of published diagnostic assessments,
      clinical trials, and guidelines from 1985 to 2012 were reviewed and analyzed to
      assess the potential effect of MHE in the clinical practice setting. RESULTS:
      Accumulating evidence suggests that MHE has a substantial negative effect on
      patient quality of life, particularly in activities that require attention, motor
      skills, and visuospatial ability. Because MHE lacks obvious clinical signs,
      specialized testing is required for diagnosis, although there is no consensus on
      the most appropriate assessment tools or treatment algorithms. Compounds derived
      from bacterial activities in the gut can cause neurochemical changes in the
      brain. These gut-derived toxins (eg, ammonia, benzodiazepine-like substances) are
      implicated in the pathophysiology of OHE. In patients with liver disease or
      portosystemic shunting, these toxins are inefficiently detoxified, accumulate in
      the blood, cross the blood-brain barrier, and result in abnormalities such as
      altered neurotransmission, astrocyte swelling, and impaired energy metabolism.
      Therefore, treatments have focused on toxin removal and the management of gut
      flora levels. Several studies have indicated that probiotics, nonabsorbable
      disaccharides, and nonsystemic antibiotics can all be effective in improving the
      symptoms of MHE. Furthermore, prophylaxis for MHE in patients with cirrhosis
      could serve to improve patient quality of life while preventing its transition to
      OHE. CONCLUSIONS: Although MHE detection and treatment is not currently the
      standard of care, several therapies have been reported to improve cognitive
      function and quality of life. Interest is increasing in the proactive diagnosis
      and management of MHE in the clinical practice setting. However, research is
      required to determine the conditions under which the putative benefits of
      prophylactic MHE therapy outweigh the costs.

PMID- 23972579
TI  - Effects of dividing amlodipine daily doses on trough drug concentrations and
      blood pressure control over a 24-hour period.
AB  - BACKGROUND: In the treatment of hypertension, once-daily administration of long
      acting antihypertensive drugs has been recommended for the improvement of
      treatment adherence; however, it is unclear whether dividing daily doses has the
      additional benefit of more ideal blood pressure (BP) control over a 24-hour
      period. OBJECTIVE: The aim of the study was to investigate whether dividing a 10
      mg daily dose of amlodipine, a long-acting calcium channel blocker, is associated
      with increased trough plasma amlodipine concentrations, reduced arterial
      stiffness, and improved BP control over a 24-hour period. METHODS: Outpatients
      with essential hypertension were included this open-label, 2-period crossover
      study. The patients were administered amlodipine 10 mg/d in 2 divided doses for 8
      weeks. At week 4, blood was collected just before amlodipine administration for
      the evaluation of trough plasma amlodipine concentrations. At week 8, 24-hour,
      daytime, nighttime, and early morning BP, as well as arterial stiffness, were
      measured using ambulatory BP monitoring (ABPM) and cardio-ankle vascular index
      (CAVI), respectively. In the subsequent study period, amlodipine 10 mg/d was
      administered once daily, and the same tests were performed at the same timings as
      in period 1. RESULTS: Ten patients were enrolled (7 men, 3 women; mean age, 61.0
      [15.3] years). Mean 24-hour BP with twice-daily administration was not
      significantly lower than that with once-daily administration (129.7 [7.3]/80.1
      [7.9] mm Hg vs 130.5 [11.8]/80.1 [7.9] mm Hg, respectively). Similarly, there
      were no significant differences in daytime, nighttime, or early morning BP
      between twice- and once-daily administration. In addition, the differences in
      trough plasma amlodipine concentrations (22.37 [7.66] ng/mL vs 20.57 [8.22]
      ng/mL) and CAVI values (8.2 [1.8] vs 8.5 [1.0]) were not significantly different
      between twice- and once-daily administration. CONCLUSIONS: Administering
      amlodipine in 2 divided doses was not associated with increased trough plasma
      amlodipine concentrations, reduced arterial stiffness, or improved BP control
      over a 24-hour period in patients with essential hypertension.

PMID- 23972580
TI  - Commentary to the paper "Morphogenetic action through flux-limited spreading".
AB  - This note presents a brief commentary to a paper by Verbeni et al. (2013) [8]
      concerning flux-limited interpretation of morphogenetic actions. After a concise
      excursus on the nonlinearity features in diffusion phenomena, three key questions
      are posed to Verbeni et al. (2013) [8]. The final comments looks ahead to
      research perspective concerning the interactions between biology and mathematics.

PMID- 23972581
TI  - Estimating the contribution of lightning to microbial evolution: guidance from
      the Drake equation: comment on "Lightning-triggered electroporation and
      electrofusion as possible contributors to natural horizontal gene transfer" by
      Tadej Kotnik.

PMID- 23972583
TI  - New guidelines for management of concussion in sport: special concern for youth.
AB  - The incidence of sports related concussion appears to be increasing, raising
      alarm over long-term consequences of these head injuries on cognitive function in
      youth. The American Academy of Neurology (AAN) has recently revised its position
      statement on concussion in sports, reflecting the burgeoning scientific evidence
      on its epidemiology, neurophysiology and prognosis. The AAN, along with other
      scientific organizations addressing concussion policy, has abandoned the use of
      algorithms for assigning a grade to concussions and instead stresses an
      individualized approach to concussion management. Recent evidence suggests that
      children and adolescents may be more susceptible to concussions from head blows,
      and may take longer to recover, than adults. Young women in certain sports also
      appear to be more susceptible to concussion than young men. The AAN recommends a
      more conservative approach to management of sports concussion in children and
      adolescents. Under no circumstances should a young athlete be allowed to
      participate in sport while still symptomatic. The use of standardized assessment
      tools is recommended to aid the healthcare provider in assessing the young
      athlete's recovery. 

PMID- 23972582
TI  - A research agenda for adolescent-centered primary care in the United States.
AB  - Little attention has been given to how primary care can be transformed to better
      meet the needs of adolescents. To help generate the evidence needed, The National
      Alliance to Advance Adolescent Health convened an invitational conference in 2012
      in Washington, DC. Participants from various disciplines identified a set of
      prioritized recommendations pertaining to 3 topics: increasing adolescent and
      parent engagement and self-care management; improving preventive care and
      identifying conditions early; and integrating physical, behavioral, and
      reproductive health services. This commentary includes the top three
      recommendations for each topic area and concludes with a brief examination of
      federal and private funding prospects. 

PMID- 23972584
TI  - Screening by the patient health questionnaire-9 items for Indian adolescents with
      depression.

PMID- 23972585
TI  - Letter to the editor.

PMID- 23972586
TI  - Organ equivalent doses of patients undergoing chest computed tomography:
      measurements with TL dosimeters in an anthropomorphic phantom.
AB  - Dose reduction in patients undergoing computed tomography (CT) examinations has
      become a concern in many countries. CT dosimetric quantities were defined aiming
      optimization of CT procedures, organ absorbed doses and effective doses have been
      calculated for radiation risk assessments in patients. In this work, an
      experimental methodology was established for measuring organ doses with
      thermoluminescent (TL) dosimeters in an anthropomorphic phantom for routine CT
      chest examinations. Results may be useful for validating computational software
      used for CT dose calculations. 

PMID- 23972587
TI  - Demyelinating encephalopathy in adult onset Still's disease: case report and
      review of the literatures.

PMID- 23972588
TI  - Insight into illness in late-life schizophrenia: a function of illness severity
      and premorbid intellectual function.
AB  - Impaired insight into illness is a common but poorly understood phenomenon in
      schizophrenia. Several studies in midlife adults with schizophrenia have reported
      an association between impaired insight and illness severity, executive
      dysfunction, premorbid intellectual function, and to a lesser degree attention.
      Aging is associated with a decline in attention and executive function. Thus, the
      relationship between cognition and insight is expected to differ between younger
      and older adults with schizophrenia. This study assessed this relationship among
      50 patients with schizophrenia 60 years and older. Insight was explained by
      illness severity (16.2% of the variance) and premorbid intellectual function
      (23.9% of the variance), but not by attention or executive function. Our findings
      suggest that the predictors of insight in schizophrenia differ early and later in
      life. In particular, insight's association with attention and executive function
      observed in younger patients is attenuated by age-related changes in cognition.
      In contrast, premorbid intellectual function continues to be a strong predictor
      of insight in late life, which highlights the need to better understand and
      enhance cognitive function early in the course of schizophrenia.

PMID- 23972589
TI  - Presynaptic proteoglycans: sweet organizers of synapse development.
AB  - Synaptic adhesion molecules control neuronal synapse development. In this issue
      of Neuron, Siddiqui et al. (2013) and de Wit et al. (2013) demonstrate that
      LRRTM4, a postsynaptic adhesion molecule, trans-synaptically interacts with
      presynaptic heparan sulfate proteoglycans (HSPGs) to promote synapse development.

PMID- 23972590
TI  - A spoonful of bitter helps the sugar response go down.
AB  - Sweet and bitter taste distinguishes good food sources from potential toxins, but
      what happens when these tastants are mixed? In this issue of Neuron, Jeong et al.
      (2013) show that in Drosophila, bitter compounds act through an extracellular
      odorant-binding protein to inhibit sweet-responsive neurons and block the
      response to sweet taste. 

PMID- 23972591
TI  - Scene areas in humans and macaques.
AB  - In this issue of Neuron, Kornblith et al. (2013) identify two regions in macaque
      occipitotemporal cortex that encode both spatial and nonspatial aspects of visual
      scenes and might be the homolog of the human parahippocampal place area. 

PMID- 23972593
TI  - The basal ganglia's contributions to perceptual decision making.
AB  - Perceptual decision making is a computationally demanding process that requires
      the brain to interpret incoming sensory information in the context of goals,
      expectations, preferences, and other factors. These integrative processes engage
      much of cortex but also require contributions from subcortical structures to
      affect behavior. Here we summarize recent evidence supporting specific
      computational roles of the basal ganglia in perceptual decision making. These
      roles probably share common mechanisms with the basal ganglia's other, more well
      established functions in motor control, learning, and other aspects of cognition
      and thus can provide insights into the general roles of this important
      subcortical network in higher brain function. 

PMID- 23972594
TI  - Molecular bases for the asynchronous activation of sodium and potassium channels
      required for nerve impulse generation.
AB  - Most action potentials are produced by the sequential activation of voltage-gated
      sodium (Nav) and potassium (Kv) channels. This is mainly achieved by the rapid
      conformational rearrangement of voltage-sensor (VS) modules in Nav channels, with
      activation kinetics up to 6-fold faster than Shaker-type Kv channels. Here, using
      mutagenesis and gating current measurements, we show that a 3-fold acceleration
      of the VS kinetics in Nav versus Shaker Kv channels is produced by the
      hydrophilicity of two "speed-control" residues located in the S2 and S4 segments
      in Nav domains I-III. An additional 2-fold acceleration of the Nav VS kinetics is
      provided by the coexpression of the beta1 subunit, ubiquitously found in mammal
      tissues. This study uncovers the molecular bases responsible for the differential
      activation of Nav versus Kv channels, a fundamental prerequisite for the genesis
      of action potentials. 

PMID- 23972592
TI  - The sensory neurons of touch.
AB  - The somatosensory system decodes a wide range of tactile stimuli and thus endows
      us with a remarkable capacity for object recognition, texture discrimination,
      sensory-motor feedback and social exchange. The first step leading to perception
      of innocuous touch is activation of cutaneous sensory neurons called low
      threshold mechanoreceptors (LTMRs). Here, we review the properties and functions
      of LTMRs, emphasizing the unique tuning properties of LTMR subtypes and the
      organizational logic of their peripheral and central axonal projections. We
      discuss the spinal cord neurophysiological representation of complex mechanical
      forces acting upon the skin and current views of how tactile information is
      processed and conveyed from the spinal cord to the brain. An integrative model in
      which ensembles of impulses arising from physiologically distinct LTMRs are
      integrated and processed in somatotopically aligned mechanosensory columns of the
      spinal cord dorsal horn underlies the nervous system's enormous capacity for
      perceiving the richness of the tactile world. 

PMID- 23972595
TI  - BLA to vHPC inputs modulate anxiety-related behaviors.
AB  - The basolateral amygdala (BLA) and ventral hippocampus (vHPC) have both been
      implicated in mediating anxiety-related behaviors, but the functional
      contribution of BLA inputs to the vHPC has never been directly investigated. Here
      we show that activation of BLA-vHPC synapses acutely and robustly increased
      anxiety-related behaviors, while inhibition of BLA-vHPC synapses decreased
      anxiety-related behaviors. We combined optogenetic approaches with in vivo
      pharmacological manipulations and ex vivo whole-cell patch-clamp recordings to
      dissect the local circuit mechanisms, demonstrating that activation of BLA
      terminals in the vHPC provided monosynaptic, glutamatergic inputs to vHPC
      pyramidal neurons. Furthermore, BLA inputs exerted polysynaptic, inhibitory
      effects mediated by local interneurons in the vHPC that may serve to balance the
      circuit locally. These data establish a role for BLA-vHPC synapses in
      bidirectionally controlling anxiety-related behaviors in an immediate, yet
      reversible, manner and a model for the local circuit mechanism of BLA inputs in
      the vHPC. 

PMID- 23972596
TI  - Axin directs the amplification and differentiation of intermediate progenitors in
      the developing cerebral cortex.
AB  - The expansion of the mammalian cerebral cortex is safeguarded by a concerted
      balance between amplification and neuronal differentiation of intermediate
      progenitors (IPs). Nonetheless, the molecular controls governing these processes
      remain unclear. We found that the scaffold protein Axin is a critical regulator
      that determines the IP population size and ultimately the number of neurons
      during neurogenesis in the developing cerebral cortex. The increase of the IP
      pool is mediated by the interaction between Axin and GSK-3 in the cytoplasmic
      compartments of the progenitors. Importantly, as development proceeds, Axin
      becomes enriched in the nucleus to trigger neuronal differentiation via beta
      catenin activation. The nuclear localization of Axin and hence the switch of IPs
      from proliferative to differentiative status are strictly controlled by the Cdk5
      dependent phosphorylation of Axin at Thr485. Our results demonstrate an important
      Axin-dependent regulatory mechanism in neurogenesis, providing potential insights
      into the evolutionary expansion of the cerebral cortex. VIDEO ABSTRACT: 

PMID- 23972597
TI  - Translational control of entrainment and synchrony of the suprachiasmatic
      circadian clock by mTOR/4E-BP1 signaling.
AB  - Protein synthesis is critical for circadian clock function, but little is known
      of how translational regulation controls the master pacemaker in mammals, the
      suprachiasmatic nucleus (SCN). Here we demonstrate that the pivotal translational
      repressor, the eukaryotic translational initiation factor 4E binding protein 1
      (4E-BP1), is rhythmically regulated via the mechanistic target of rapamycin
      (mTOR) signaling in the SCN and preferentially represses vasoactive intestinal
      peptide (Vip) mRNA translation. Knockout (KO) of Eif4ebp1 (gene encoding 4E-BP1)
      leads to upregulation of VIP and higher amplitude of molecular rhythms in the
      SCN. Consequently, the 4E-BP1 null mice exhibit accelerated re-entrainment to a
      shifted light/dark cycle and are more resistant to the rhythm-disruptive effects
      of constant light. Conversely, in Mtor(+/-) mice VIP expression is decreased and
      susceptibility to the effects of constant light is increased. These results
      reveal a key role for mTOR/4E-BP1-mediated translational control in regulating
      entrainment and synchrony of the master clock. 

PMID- 23972598
TI  - An odorant-binding protein required for suppression of sweet taste by bitter
      chemicals.
AB  - Animals often must decide whether or not to consume a diet that contains
      competing attractive and aversive compounds. Here, using the fruit fly,
      Drosophila melanogaster, we describe a mechanism that influences this decision.
      Addition of bitter compounds to sucrose suppressed feeding behavior, and this
      inhibition depended on an odorant-binding protein (OBP) termed OBP49a. In wild
      type flies, bitter compounds suppressed sucrose-induced action potentials, and
      the inhibition was impaired in Obp49a mutants. However, loss of OBP49a did not
      affect action potentials in sugar- or bitter-activated gustatory receptor neurons
      (GRNs) when the GRNs were presented with just one type of tastant. OBP49a was
      expressed in accessory cells and acted non-cell-autonomously to attenuate nerve
      firings in sugar-activated GRNs when bitter compounds were combined with sucrose.
      These findings demonstrate an unexpected role for an OBP in taste and identify a
      molecular player involved in the integration of opposing attractive and aversive
      gustatory inputs. 

PMID- 23972599
TI  - Interaural level difference-dependent gain control and synaptic scaling
      underlying binaural computation.
AB  - Binaural integration in the central nucleus of inferior colliculus (ICC) plays a
      critical role in sound localization. However, its arithmetic nature and
      underlying synaptic mechanisms remain unclear. Here, we showed in mouse ICC
      neurons that the contralateral dominance is created by a "push-pull"-like
      mechanism, with contralaterally dominant excitation and more bilaterally balanced
      inhibition. Importantly, binaural spiking response is generated apparently from
      an ipsilaterally mediated scaling of contralateral response, leaving frequency
      tuning unchanged. This scaling effect is attributed to a divisive attenuation of
      contralaterally evoked synaptic excitation onto ICC neurons with their inhibition
      largely unaffected. Thus, a gain control mediates the linear transformation from
      monaural to binaural spike responses. The gain value is modulated by interaural
      level difference (ILD) primarily through scaling excitation to different levels.
      The ILD-dependent synaptic scaling and gain adjustment allow ICC neurons to
      dynamically encode interaural sound localization cues while maintaining an
      invariant representation of other independent sound attributes. 

PMID- 23972600
TI  - A pair of interneurons influences the choice between feeding and locomotion in
      Drosophila.
AB  - The decision to engage in one behavior often precludes the selection of others,
      suggesting cross-inhibition between incompatible behaviors. For example, the
      likelihood to initiate feeding might be influenced by an animal's commitment to
      other behaviors. Here, we examine the modulation of feeding behavior in the fruit
      fly, Drosophila melanogaster, and identify a pair of interneurons in the ventral
      nerve cord that is activated by stimulation of mechanosensory neurons and
      inhibits feeding initiation, suggesting that these neurons suppress feeding while
      the fly is walking. Conversely, inhibiting activity in these neurons promotes
      feeding initiation and inhibits locomotion. These studies demonstrate the mutual
      exclusivity between locomotion and feeding initiation in the fly, isolate
      interneurons that influence this behavioral choice, and provide a framework for
      studying the neural basis for behavioral exclusivity in Drosophila. 

PMID- 23972601
TI  - Evidence for hubs in human functional brain networks.
AB  - Hubs integrate and distribute information in powerful ways due to the number and
      positioning of their contacts in a network. Several resting-state functional
      connectivity MRI reports have implicated regions of the default mode system as
      brain hubs; we demonstrate that previous degree-based approaches to hub
      identification may have identified portions of large brain systems rather than
      critical nodes of brain networks. We utilize two methods to identify hub-like
      brain regions: (1) finding network nodes that participate in multiple subnetworks
      of the brain, and (2) finding spatial locations in which several systems are
      represented within a small volume. These methods converge on a distributed set of
      regions that differ from previous reports on hubs. This work identifies regions
      that support multiple systems, leading to spatially constrained predictions about
      brain function that may be tested in terms of lesions, evoked responses, and
      dynamic patterns of activity. 

PMID- 23972603
TI  - Distribution of GnRH in the brain of the freshwater teleost Astyanax altiparanae.
AB  - GnRH is well known as a key decapeptide neurohormone involved in reproduction,
      stimulating the pituitary gland to release gonadotropins (LH and FSH), which, in
      turn, regulate steroidogenesis and gametogenesis. However, in addition to its
      reproductive functions, GnRH displays neuromodulatory roles with implications for
      sexual behavior. The pattern of distribution in the brain of GnRH may help reveal
      GnRH specific functions. Therefore, the main emphasis of this study is to detect
      the presence and distribution of GnRH in the brain of the freshwater teleost
      Astyanax altiparanae ("lambari"). The immunohistochemical method of peroxidase
      with an antibody raised against GnRH3 was used to detect the location of GnRHs in
      the brain and pituitary gland. Immunoreactivity to GnRH was found in the
      following encephalic areas: olfactory bulb, terminal nerve ganglion, preoptic
      area, nucleus of midbrain tegmentum, but also in torus longitudinalis, glomerular
      nucleus, and central and dorsal posterior nuclei of dorsal thalamus. In addition,
      cell bodies from neurons in the parvocellular and magnocellular periventricular
      nuclei and ventral tuberal nucleus along with many fibers including ones
      innervating the neurohypophysis were immunoreactive to a GnRH antiserum that
      detects all known eight GnRH peptides in teleosts. This is the first study
      describing the distribution of the complete GnRH system in the brain of A.
      altiparanae, which has great importance for aquaculture and ecology, and
      represents one of the major orders of South American teleosts--the Characiformes.

PMID- 23972602
TI  - Neural primacy of the salience processing system in schizophrenia.
AB  - For effective information processing, two large-scale distributed neural networks
      appear to be critical: a multimodal executive system anchored on the dorsolateral
      prefrontal cortex (DLPFC) and a salience system anchored on the anterior insula.
      Aberrant interaction among distributed networks is a feature of psychiatric
      disorders such as schizophrenia. We used whole-brain Granger causal modeling
      using resting fMRI and observed a significant failure of both the feedforward and
      reciprocal influence between the insula and the DLPFC in schizophrenia. Further,
      a significant failure of directed influence from bilateral visual cortices to the
      insula was also seen in patients. These findings provide compelling evidence for
      a breakdown of the salience-execution loop in the clinical expression of
      psychosis. In addition, this offers a parsimonious explanation for the often
      observed "frontal inefficiency," the failure to recruit prefrontal system when
      salient or novel information becomes available in patients with schizophrenia. 

PMID- 23972604
TI  - Electron energy-loss spectroscopy of V2O5 nanofibers synthesized by electro
      spinning.
AB  - The dielectric properties of V2O5 nanofibers, synthesized by the electrospinning
      method, are studied by analyzing the low-loss region of the electron energy loss
      spectroscopy (EELS) in a transmission electron microscope. A comparison of
      experimental EELS spectra and ab initio density-functional theory calculations
      (WIEN2k code) within the Generalized Gradient Approximation (GGA) is presented,
      having found an excellent agreement between them. Although the experimental EELS
      has been acquired for the nanoparticles composing the fibers, and numerical
      calculations were carried out for bulk material, agreement between experimental
      and calculated results shows that no difference exists between the electronic
      structure in calculated bulk material and the nanoparticles. Furthermore, our
      results from EELS confirm that we accomplished the expected crystalline phase.
      The origins of interband transitions are identified in the electronic band
      structure by calculating the partial imaginary part of the dielectric function
      and the partial density of states.

PMID- 23972614
TI  - Helicobacter pylori induces type 4 secretion system-dependent, but CagA
      independent activation of IkappaBs and NF-kappaB/RelA at early time points.
AB  - Colonization of the gastric epithelium by Helicobacter pylori induces the
      transcription factor nuclear factor of kappa light polypeptide gene enhancer in B
      cells (NF-kappaB) and the innate immune response. Virulent strains of H. pylori
      carry a cag pathogenicity island (cagPAI), which encodes a type IV secretion
      system (T4SS). Recent publications have shown controversial data regarding the
      role of the T4SS and the effector protein cytotoxin associated gene A (CagA),
      which becomes translocated by the T4SS into the eukaryotic epithelial cell, in H.
      pylori-induced NF-kappaB activation. Thus, this study analyses by using three
      different H. pylori strains (P1, B128 and G27) whether CagA is required to
      initiate activation of different molecules of inhibitors of kappa B (IkappaB) and
      the NF-kappaB transcription factor RelA. We provide experimental evidence that H.
      pylori induces phosphorylation of NF-kappaB inhibitors IkappaBalpha, IkappaBbeta
      and IkappaBE, and degradation of IkappaBalpha. Further, H. pylori stimulates
      phosphorylation of RelA at amino acids S536, S468 and S276, promotes DNA binding
      of RelA, and interleukin 8 (IL-8) gene expression in a T4SS-, but CagA
      independent manner at early time points. 

PMID- 23972615
TI  - The contribution of common rpsL mutations in Escherichia coli to sensitivity to
      ribosome targeting antibiotics.
AB  - Point mutations in the rpsL gene encoding ribosomal protein S12 can generate
      resistance to streptomycin, resulting in rapid emergence of resistance to this
      antibiotic during treatment. In this work, we demonstrate that while spontaneous
      rpsL mutants in Escherichia coli are resistant to streptomycin, they are more
      sensitive to the ribosome-targeting antibiotics chloramphenicol, tetracycline and
      erythromycin. Moreover, combinations of these antibiotics, even in low
      concentrations were enough to achieve complete growth inhibition of both wild
      type and rpsL mutant strains. Thus, combining ribosome-targeting drugs can be
      used as a new treatment strategy that may be effective against streptomycin
      resistant ribosome mutants.

PMID- 23972616
TI  - Serological follow-up after non-typhoid salmonella infection in humans using a
      mixed lipopolysaccharide ELISA.
AB  - In industrialized countries, non-typhoid salmonella are a frequent cause of
      bacterial gastroenteritis. Diagnosis is usually made by stool culture, which is
      labour-intensive and time-consuming. Sensitivity depends on handling of stool
      samples and delay from illness onset to sampling. We developed an indirect mixed
      enzyme-linked immunosorbent assay (ELISA) for the detection of human serum
      antibodies against lipopolysaccharide antigens of the two predominant serovars,
      Salmonella serovar Enteritidis (S. Enteritidis) and S. Typhimurium. We measured
      IgA, IgM and IgG in 964 sera from 302 patients with stool culture-confirmed acute
      salmonella gastroenteritis, in 300 sera from healthy blood donors, and in 147
      sera from patients with antibodies against other bacteria. Patient sera were
      collected within 1 month and approximately 3, 6, and 12 months after illness
      onset. For sera collected <= 30 days of onset, sensitivity of the ELISA was 92%
      for S. Enteritidis and 86% for S. Typhimurium, with a specificity of 95% for both
      serovars. The mixed ELISA is a useful additional tool for the diagnosis of acute
      salmonella gastroenteritis. It allows rapid analysis of multiple samples, thus
      can be used for sero-epidemiological studies of large population-based serum
      collections in order to estimate the population incidence of salmonella
      infections. Another application is aetiological diagnostics in patients with
      suspected post-infectious complications such as reactive arthritis, even when
      faecal shedding of salmonella has ceased.

PMID- 23972618
TI  - Cryptosporidium species from human immunodeficiency-infected patients with
      chronic diarrhea in Jakarta, Indonesia.
AB  - PURPOSE: Cryptosporidium is an opportunistic parasite that manifests as chronic
      and severe diarrhea in the immune-compromised subject. We investigated the
      species of Cryptosporidium to understand the epidemiology, mode of transmission,
      response to treatment, and prevention. METHODS: Polymerase chain
      reaction/restriction fragment length polymorphism of the 18 S rRNA gene and
      sequencing were performed on 41 Cryptosporidium-positive stools from 36 patients
      with HIV AIDS, which comprised 36 pretreatment stools and 5 stools after
      treatment with Paromomycin. RESULTS: C. hominis, C. meleagridis, C. felis, and C.
      parvum were detected; 28 of 36 (77.7%) patients were infected with C. hominis and
      two (5.5%) patients with multiple species of Cryptosporidium. Treatment with
      Paromomycin resulted in different outcomes, perhaps because patients harbored
      other intestinal parasitic infections. CONCLUSIONS: Multiple infection with
      various Cryptosporidium species in the presence of other intestinal parasites
      occurs in patients with HIV AIDS suffering from chronic diarrhea who are severely
      immune-compromised. Common transmission of Cryptosporidium is anthroponotic.

PMID- 23972617
TI  - Clashing paradigms: an empirical examination of cultural proxies and
      socioeconomic condition shaping Latino health.
AB  - OBJECTIVE: Much debate exists regarding the role of culture versus socioeconomic
      position in shaping the health of Latino populations. We propose that both may
      matter for health and explicitly test their independent and joint effects on
      smoking and physical activity. METHODS: We used the 2010 National Health
      Interview Survey, a population-based survey of the U.S. population, to estimate
      the prevalence of smoking and physical activity by language use (cultural proxy)
      and education among Latino adults (n = 4929). We fit log binomial regression
      models to estimate prevalence ratios and test for interaction. RESULTS: English
      language use and educational attainment were each independently associated with
      smoking and physical activity. Joint effect models showed that individuals with
      both greater use of the English language and low levels of education were nearly
      three times more likely to smoke (prevalence ratio, 2.59; 95% confidence
      interval, 1.83-3.65) than those with low English language use and high education
      (referent group); high acculturation and high education were jointly associated
      with increased activity (prevalence ratio 2.24, 95% confidence interval, 1.79
      2.81). CONCLUSIONS: Cultural proxies such as language use and educational
      attainment are both important determinants of health among Latinos. Their joint
      effect suggests the need to simultaneously consider Latinos' socioeconomic
      position and their increased risk of adopting health-damaging behaviors while
      addressing culturally-specific factors that may mitigate risk.

PMID- 23972619
TI  - Perceived social support buffers the impact of PTSD symptoms on suicidal
      behavior: implications into suicide resilience research.
AB  - BACKGROUND: A growing body of research has highlighted the importance of
      identifying resilience factors against suicidal behavior. However, no previous
      study has investigated potential resilience factors among individuals with
      Posttraumatic Stress Disorder (PTSD). The aim of this study was to examine
      whether perceived social support buffered the impact of PTSD symptoms on suicidal
      behavior. METHODS: Fifty-six individuals who had previously been exposed to a
      traumatic event and reported PTSD symptoms in the past month (n = 34, 60.7%
      participants met the full criteria for a current PTSD diagnosis) completed a
      range of self-report measures assessing PTSD symptoms, perceived social support
      and suicidal behavior. Hierarchical regression analyses were conducted to examine
      whether perceived social support moderates the effects of PTSD symptoms on
      suicidal behavior. RESULTS: The results showed that perceived social support
      moderated the impact of the number and severity of PTSD symptoms on suicidal
      behavior. For those who perceived themselves as having high levels of social
      support, an increased number and severity of PTSD symptoms were less likely to
      lead to suicidal behavior. CONCLUSIONS: The current findings suggest that
      perceived social support might confer resilience to individuals with PTSD and
      counter the development of suicidal thoughts and behaviors. The milieu of social
      support potentially provides an area of further research and an important aspect
      to incorporate into clinical interventions for suicidal behavior in PTSD or
      trauma populations.

PMID- 23972620
TI  - Penehyclidine hydrochloride ameliorates renal ischemia-reperfusion injury in
      rats.
AB  - BACKGROUND: Renal ischemia-reperfusion (I/R) injury is a major cause of acute
      kidney failure by mechanisms that involve oxidative stress, inflammation, and
      apoptosis. Penehyclidine hydrochloride (PHC), a selective anticholinergic agent,
      possesses anti-inflammatory, antioxidative stress, and antiapoptotic effects.
      Therefore, we investigated the ability of PHC to ameliorate renal I/R injury in
      Sprague-Dawley rats. MATERIALS AND METHODS: Rats were randomly assigned to three
      groups (35 rats per group): sham operated, saline-treated I/R, and PHC-treated
      I/R. After removing the right kidney, renal I/R injury was induced by clamping
      the left renal artery for 45 min followed by reperfusion. The rats were
      administered PHC (0.45 mg/kg, intravenously) or saline 30 min before renal
      ischemia. The blood and kidneys were harvested at 1, 3, 6, 12, or 24 h after
      reperfusion. Renal function and histologic changes were assessed. Markers of
      oxidative stress, inflammation, and apoptosis in the kidneys were also measured.
      RESULTS: PHC treatment significantly attenuated renal dysfunction and histologic
      damage caused by I/R injury. The treatment also decreased malondialdehyde level
      and attenuated the reduction in superoxide dismutase activity in the kidney.
      Moreover, the levels of activated p38 mitogen-activated protein kinase, nuclear
      factor kappa B, and caspase 3 were lower in the PHC-treated animals. CONCLUSIONS:
      PHC protected rat kidneys from I/R injury by attenuating oxidative stress,
      inflammatory response, and apoptosis. Thus, PHC may represent a novel practical
      strategy for the treatment of renal I/R injury.

PMID- 23972621
TI  - Reconciling the effects of inflammatory cytokines on mesenchymal cell osteogenic
      differentiation.
AB  - Therapies using mesenchymal stem cells are a popular current avenue for
      development and utilization, especially in the fields of de novo tissue
      engineering (Sanchez-Ramos J, Song S, Cardozo-Pelaez F, et al. Adult bone marrow
      stromal cells differentiate into neural cells in vitro. Exp Neurol 2000;164:247.)
      or tissue regeneration after physical injury (Kitoh H, Kitakoji T, Tsuchiya H, et
      al. Transplantation of marrow-derived mesenchymal stem cells and platelet-rich
      plasma during distraction osteogenesis-a preliminary result of three cases. Bone
      2004;35:892; Shumakov VI, Onishchenko NA, Rasulov MF, Krasheninnikov ME, Zaidenov
      VA. Mesenchymal bone marrow stem cells more effectively stimulate regeneration of
      deep burn wounds than embryonic fibroblasts. Bull Exp Biol Med 2003;136:192;
      Bruder SP, Fink DJ, Caplan AI. Mesenchymal stem cells in bone development, bone
      repair, and skeletal regeneration therapy. J Cell Biochem 1994;56:283.). The
      osteogenic potential of these cells is of particular interest, given their recent
      usage for the closure of critical-sized bone defects and other nonhealing bone
      scenarios such as a nonunion. Recent literature suggests that inflammatory
      cytokines can significantly impact the osteogenic potential of these cells. A
      review of relevant, recent literature is presented regarding the impact of the
      inflammatory cascade on the osteogenic differentiation of these cells and how
      this varies across species. Finally, we identify areas of conflicting or absent
      evidence regarding the behavior of mesenchymal stem cells in response to
      inflammatory cytokines.

PMID- 23972622
TI  - Sutureless anastomoses using magnetic rings in canine liver transplantation
      model.
AB  - BACKGROUND: In the first posttransplant month, the most frequent complications
      are due to technical problems related to complex vascular and bile duct
      reconstructions during the operation. Moreover, despite great improvements in
      suturing technique and materials, severe organ ischemia-reperfusion caused by
      time-consuming hand suturing is still an important factor in graft survival.
      During the operation, severe hypotension, hypoxic acidosis, hyperkalemia, and
      renal dysfunction may occur during the anhepatic phase due to the prolonged
      venous clamping time required for hand suturing. Therefore, hand suturing is a
      handicap in the development of further advancements in liver transplantation. In
      this study, we aimed to test a new "mechanical installation method" for rapid
      vascular reconstruction. METHODS: The magnetic pinning-ring device was developed
      consisting of paired magnetic rings coated with titanium oxide and embedded in a
      polypropylene shell. The rings were equipped with alternately spaced holes and
      titanium pins. Forty adult mongrel dogs were randomly divided into groups: A (n =
      16), all vascular and bile duct reconstruction by magnetic ring without venous
      bypass; B (n = 16), all vascular and bile duct reconstruction by hand suturing
      with venous bypass; C (n = 8), sham transplantation group, transection of all
      vessels and common bile duct followed by anastomosis with the magnetic rings
      without liver transplantation. From groups A and B, dogs were randomly selected
      as donors (n = 8) or recipients (n = 8) of liver transplantations. We recorded
      operation time, vascular and bile duct anastomosis time, anhepatic time,
      administration of supplemental fluids during operation, and survival; blood
      samples were collected for the detection of liver damage (alanine
      aminotransferase [ALT] and aspartate aminotransferase [AST]) and tumor necrosis
      factor alpha level. Patency was confirmed using ultrasound scans at various time
      points as late as 24 wk after surgery. Angiography was used to evaluate the
      anastomoses formed with magnetic rings. In group C, gross observation, histologic
      staining, and scanning electron microscopy were used to evaluate the vessels and
      bile ducts 12 wk postoperatively. RESULTS: In group A, the total operation time,
      inferior vena cava, and portal vein anastomosis times were significantly
      shortened, and the anhepatic phase was reduced to about one-fifth that of group
      B, which was a significant difference between the two groups (P < 0.01). The mean
      total operative time was 2.54 +/- 0.45 h. In order to maintain adequate blood
      pressure, the mean fluid volume infused was 800.56 +/- 60.56 mL in the recipients
      of group A, which was lower than that in group B (2241.67 +/- 390.78 mL, P <
      0.01). Use of a pressor agent in group A was unnecessary. After operation, five
      of eight animals in group A survived more than 7 d after operation. The main
      cause of death was acute rejection. Only three of eight animals in group B
      survived more than 1 wk after operation due to chronic anastomotic bleeding,
      kidney failure, heart failure, and gastrointestinal bleeding. There was a
      statistically significant difference (P < 0.01) between the short-term survival
      rate in the two groups (75.0% versus 37.5%). The ALT (1544.46 +/- 286.27) U/L and
      AST (1710.74 +/- 252.27) U/L levels after operation in the animals with hand
      suturing were significantly higher than those in the sutureless group (ALT =
      1116.41 +/- 210.55 U/L; AST = 1176.95 +/- 248.25) U/L after reperfusion (P <
      0.01). The serum tumor necrosis factor alpha levels (45.56 +/- 10.78) ng/L in
      group B were significantly higher than those of group A (26.64 +/- 10.84) ng/L
      after reperfusion (P < 0.01). Re-endothelialization was confirmed in all vessels
      in group C, with neither formation of aneurysms nor thickening of the vascular
      wall noted after 12 wk. The bile duct anastomoses also healed well. CONCLUSIONS:
      The magnetic pinning-ring device offers a simple, fast, reliable, and efficacious
      technique for nonsuturing vascular and bile duct anastomoses. Use of this device
      shortens operation time, maintains a high patency rate, and improves the healing
      of tissue. Application of the magnetic ring anastomosis technique can effectively
      reduce the complications caused by hand suturing, and can reduce the extent of
      ischemia-reperfusion injury, leading to smoother operations and improved
      prognosis.

PMID- 23972623
TI  - Cognitive impairment and antiretroviral treatment in a Peruvian population of
      patients with human immunodeficiency virus.
AB  - BACKGROUND: HIV-associated cognitive impairment occurs even in the early stages
      of infection. Short-term memory, psychomotor speed, attention, and executive
      functioning are the main capacities affected. Controversy exists regarding
      whether highly active antiretroviral therapy (HAART) is helpful in combating this
      process. The objective of the present study is to determine the association
      between cognitive impairment and HAART in HIV-infected patients from Hospital
      Regional de Huacho. METHODS: Prospective study of HIV patients meeting criteria
      to start HAART. Twenty-one HIV-positive patients were recruited between April and
      July 2011. Researchers administered a standardised neuropsychological test
      battery before and 4 weeks after onset of HAART. Psychomotor speed, executive
      function, short term memory (visual and verbal), attention, and visuospatial
      performance were evaluated. RESULTS: Nineteen patients completed the study (14
      males and 5 females). In the pre-HAART evaluation, most patients scored below
      average on the executive function and psychomotor speed subtests. Psychomotor
      speed and immediate visual memory improved significantly after four months of
      treatment with HAART. CONCLUSIONS: Some degree of cognitive decline may present
      even in the early and asymptomatic stages of HIV infection. The benefits of
      antiretroviral treatment for cognitive performance can be detected after only a
      few weeks of follow-up.

PMID- 23972624
TI  - Reply to "informal caregivers network of patients with dementia in Alicante
      province, characteristics description".

PMID- 23972625
TI  - Transient ischaemic attack secondary to extracranial carotid artery aneurysm.

PMID- 23972626
TI  - Biomechanical comparison of the pullout strengths of C1 lateral mass screws and
      C1 posterior arch screws.
AB  - BACKGROUND CONTEXT: Conditions of the atlantoaxial complex requiring internal
      stabilization can result from trauma, malignancy, inflammatory diseases, and
      congenital malformation. Several techniques have been used for stabilization and
      fusion. Posterior wiring is biomechanically inferior to screw fixation. C1
      lateral mass screws and C1 posterior arch screws are used for instrumentation of
      the atlas. Previous studies have shown that unicortical C1 lateral mass screws
      are biomechanically stable for fixation. No study has evaluated the biomechanical
      stability of C1 posterior arch screws or compared the two techniques. PURPOSE:
      The purpose of the study was to assess the differences in the pullout strength
      between C1 lateral mass screws and C1 posterior arch screws. STUDY DESIGN:
      Biomechanical testing of pullout strengths of the two atlantal screw fixation
      techniques. METHODS: Thirteen fresh human cadaveric C1 vertebrae were harvested,
      stripped of soft tissues, evaluated with computed tomography for anomalies, and
      instrumented with unicortical C1 lateral mass screws on one side and unicortical
      C1 posterior arch screws on the other. Screw placement was confirmed with
      postinstrumentation fluoroscopy. Specimens were divided in the sagittal plane and
      potted in polymethylmethacrylate. Axial load to failure was applied with a
      material testing device. Load displacement curves were obtained, and the results
      were compared with Student t test. DePuy Spine, Inc. (Raynham, MA, USA) provided
      the hardware used in this study. RESULTS: Mean pullout strength of the C1 lateral
      mass screws was 821 N (range 387-1,645 N +/- standard deviation [SD] 364). Mean
      pullout strength of the posterior arch screws was 1,403 N (range 483-2,200 N +/-
      SD 609 N). The difference was significant (p=.009). Five samples (38%) in the
      posterior arch group experienced bone failure before screw pullout. CONCLUSIONS:
      Both unicortical lateral mass screws and unicortical posterior arch screws are
      viable options for fixation in the atlas. Unicortical posterior arch screws have
      superior resistance to pullout via axial load compared with unicortical lateral
      mass screws in the atlas.

PMID- 23972627
TI  - Pharmacophysiology of bone and spinal fusion.
AB  - BACKGROUND CONTEXT: In recent years, the number of complex spinal surgeries has
      increased significantly in the elderly population, where the prevalence of low
      bone density is highest. Consequently, spine surgeons often treat osteoporotic
      patients who are associated with higher rates of instrumentation failure.
      Therefore, establishing a successful fusion requires an appropriate substrate for
      bone formation and local bone remodeling. The fusion process can be supported by
      therapies that seek to shift the balance of bone homeostasis to increased
      formation and reduced resorption. PURPOSE: Thorough understanding of the
      physiology of bone formation and adjunctive therapies can help improve fusion
      rates. Therefore, we present a thorough review of the latest pharmacologic agents
      used to enhance bone strength and surgical spinal fusion. METHODS: Systematic
      review of literature. RESULTS: Current knowledge on bone physiology has led to
      the development of several pharmacologic agents that enhance bone formation and
      strengthen the human skeleton. At present, natural supplements of vitamin D and
      calcium or synthetic medications like bisphosphonates are widely used before and
      after spine surgeries to enhance bone fusion. Additional physiologic agents,
      including testosterone, parathyroid hormone, calcitonin, and growth hormone, have
      been shown to improve bone mass density or spinal fusion in both animal and human
      studies. As in other medical fields, gene therapy has shown viability and promise
      with the use of both viral and nonviral vectors. CONCLUSIONS: Through the
      understanding of bone physiology, numerous natural and synthetic pharmacologic
      agents have been developed to enhance the body's skeleton and to improve outcomes
      of spinal fusion surgery.

PMID- 23972628
TI  - Determination of the prevalence of whole blood taurine in Irish wolfhound dogs
      with and without echocardiographic evidence of dilated cardiomyopathy.
AB  - OBJECTIVES: Taurine plays an important role in maintaining myocardial function.
      Irish wolfhound dogs (IW) are at risk for dilated cardiomyopathy (DCM), but a
      relationship between whole blood taurine (WBT) deficiency and DCM has not been
      established. Our aim was to determine prevalence of WBT deficiency in IW with and
      without DCM and assess its association with diet. ANIMALS: 115 privately owned
      IW. METHODS: Whole blood taurine was measured in IW that received cardiovascular
      examination. Dietary history was recorded; crude protein and energy intake were
      estimated. RESULTS: Forty-nine (42.6%) had DCM; 66 (57.4%) had no DCM. Dogs with
      DCM were older ([median; inter-quartile range or IQR] 5.3; 4.3, 6.2 years) than
      dogs without heart disease (3; 2, 4 years; P < 0.001). There was no significant
      relationship between WBT concentration and age (P = 0.64). Whole blood taurine
      was severely reduced (<130 nmol/mL) in 8 dogs (4 with and 4 without DCM) and
      moderately reduced (130-179.9 nmol/mL) in 32 dogs (12 with DCM and 20 without
      DCM). Follow up of dogs without DCM revealed that a higher proportion of dogs
      with any degree of WBT deficiency developed DCM later compared to dogs with
      normal WBT (P < 0.001). CONCLUSIONS: Whole blood taurine deficiency occurred in
      IW with and without DCM. Based on taurine measurement on a single occasion, there
      was no clear relationship between low WBT and presence of DCM in this population.
      Regardless of WBT, DCM affected predominantly older dogs, suggesting a relatively
      late onset disease in the IW.

PMID- 23972629
TI  - [Hydroxyethylstarches and renal failure: to keep the reason is a necessity].

PMID- 23972630
TI  - [I'm ready to add a simple test for my anesthesia consultation to screen patients
      at risk to develop cognitive dysfunction].

PMID- 23972631
TI  - [Proceedings of the 19th Days of the French Society for the Computer and
      Monitoring in Anesthesia and Resuscitation (Sfimar)].

PMID- 23972632
TI  - Transesophageal ecocardiography: the correct intraoperative way to detect the
      source of peripheral embolism in an emergency.
AB  - Arterial thromboembolism in patients with an unknown source of embolization is
      associated with significant morbidity and mortality. Once the acute process has
      been treated, a search of the offending embolic source must be conducted to
      prevent additional episodes. The most common sources of peripheral embolism
      include intracardiac thrombi (>85%), thrombus within arterial aneurysm, thrombus
      overlying complex atherosclerotic plaques, and paradoxical embolization from deep
      venous thrombus. A strong association has been shown between protruding,
      noncalcified plaques>4 cm in the aorta detected by transesophageal
      echocardiography and the risk of embolism. Moreover, as many as 25-50% of
      protruding plaques may have superimposed mobile thrombi ranging from one to
      several centimeters, and this imparts a high embolic risk. The formation of
      thrombi in morphologically normal aorta is a rare event. We report a case of
      peripheral embolization in a young man caused by a thrombus in the descending
      aorta detected by transesophageal echocardiography.

PMID- 23972633
TI  - Arterial thoracic outlet syndrome: a 32-year experience.
AB  - BACKGROUND: Clinical manifestations of thoracic outlet syndrome (TOS) differ
      depending on the compromised anatomic structure. Arterial TOS is the least common
      (1-5% of all cases of TOS), yet the most threatening, due to the risk of limb
      loss. METHODS: We conducted a retrospective review of consecutive patients
      treated for arterial TOS between January 1979 and June 2012. Medical records and
      diagnostic images were reviewed, and follow-up was obtained. RESULTS: Nineteen
      procedures were performed in 18 patients for symptomatic arterial TOS. The
      average age was 34 years (range 16-69 years), and 12 patients were female
      (63.2%). Surgical indications were upper limb critical ischemia in 8 (acute in 5
      cases and acute-on-chronic in 3 cases) and claudication in 11. Imaging studies
      revealed a subclavian aneurysm in 7 patients, stenosis in 4 patients, and 2
      patients with subclavian artery occlusion. The 6 remaining cases had symptoms
      caused by arterial compression in dynamic studies without arterial wall damage at
      rest. All limbs underwent surgery with outlet decompression; in addition, 13
      underwent arterial reconstruction, and 7 were treated for distal embolic
      complications. There were no deaths, amputations, or early reoperations; 1
      patient was readmitted 2 weeks after surgery for chylothorax, which resolved with
      conservative measures. During a mean follow-up of 155.8+/-103.1 months, 1 patient
      underwent successful reintervention at 4 months for bypass occlusion.
      CONCLUSIONS: Arterial TOS is an infrequent but relevant manifestation of TOS. An
      accurate and early diagnosis allows for timely surgery and adequate results, as
      shown in this group of patients.

PMID- 23972634
TI  - Successful repair of bilateral common carotid artery dissections from hanging.
AB  - The management of blunt carotid artery dissections caused by hanging remains
      controversial, especially with regard to diagnostic work-up and treatment
      options. We present 2 men, 49 and 41 years of age, who were treated for bilateral
      common carotid artery dissection caused by strangulation. In the first patient,
      additional cricotracheal separation and blunt thyroid gland trauma was observed.
      Bilateral saphenous vein graft interposition was accomplished in both patients.
      In the first patient, tracheal repair and suture of the thyroid gland completed
      the procedure. At 1 year of follow-up, both patients were capable of managing
      their lives independently. A systematic review of the literature on managing near
      hanging and nonfatal strangulation victims is included in this report to allow
      this case series to be put into perspective. 

PMID- 23972635
TI  - Impact of an intensive 2-day endovascular training course on technical
      performance of trainees.
AB  - BACKGROUND: The objective of this study was to evaluate the effect of a 2-day
      international endovascular training course on the performance of trainees as
      compared with a control group, assessed in a bench model-based task using an
      objective structured evaluation protocol. METHODS: A total of 50 trainees, 28
      course participants of 2 consecutive identical courses and a control group of 22
      participants with a similar level of experience without course attendance,
      underwent baseline and final assessment (simulated arterial access task). The
      evaluation form consisted of a global assessment (GA), task-specific checklist
      percentage score (CL), and global rating scale percentage score (GR), with both
      percentage scores ranging from 0% (worst performance) to 100% (best performance).
      RESULTS: Course participants were more likely to pass the GA at final testing
      than the control group (odds ratio=59; 95% confidence interval [CI] 9.5-656;
      P<0.001). The estimated difference in percentage score at final testing between
      course participants and the control group was 26% (95% CI 18-34; P<0.001) for the
      CL and 29% (95% CI 19-40; P<0.001) for the GR. CONCLUSIONS: A 2-day structured
      endovascular training course significantly improves endovascular performance in a
      simulated environment. These results are important for the design of endovascular
      training curricula with the ultimate goal of contributing to patient safety.

PMID- 23972636
TI  - A contemporary comparative analysis of immediate postoperative prosthesis
      placement following below-knee amputation.
AB  - BACKGROUND: Despite advances in the treatment of peripheral arterial disease, a
      significant number of patients ultimately require major amputations.
      Traditionally, postoperative management of a below-knee amputation involves soft
      compressive dressings to allow for complete stump healing before initial
      prosthesis fitting. This technique is associated with a prolonged period of
      limited mobility, placing patients at risk for deconditioning or fall with a risk
      of injury to the stump. In contrast, immediate postoperative prosthesis (IPOP)
      placement allows patients to begin ambulation and rehabilitation on postoperative
      day 1, which may be of significant physiologic and psychological benefit. The
      purpose of this study is to compare the outcomes of patients undergoing IPOP
      placement to those of a historical control group managed with traditional soft
      compressive dressing placement. METHODS: Medical records of all consecutive below
      knee amputation patients who underwent IPOP (IPOP group; 37 patients, 2007-2010)
      and all patients who underwent traditional soft compressive dressing placement
      and were IPOP candidates (non-IPOP group; 35 patients, 2006-2007) were
      retrospectively reviewed. Patient comorbidities and preoperative ambulation
      status were compared between the IPOP and the non-IPOP groups. Primary outcomes
      evaluated included perioperative systemic complications, wound complications,
      need for surgical revision, and the time until placement of a definitive
      prosthesis. Data were analyzed using the chi-squared and Student's t-test.
      RESULTS: Preoperative comorbidities and patient characteristics of the 2 groups
      were similar, although the IPOP group was younger (61.5 vs. 69.0 years; P=0.01).
      Immediate perioperative systemic complication rates were not significantly
      different between the 2 groups (IPOP 29.7% vs. non-IPOP 31.4%; P=0.876).
      Postoperative wound complication rates were as follows: wound infection (IPOP
      18.9% vs. non-IPOP 25.0%; P=0.555), wound dehiscence (IPOP 29.7% vs. non-IPOP
      25.0%; P=0.673), and skin breakdown separate from the incision (IPOP 18.9% vs.
      non-IPOP 3.6%; P=0.062). Patients in the IPOP group trended towards fewer
      postoperative falls (IPOP 10.8% vs. non-IPOP 21.4%; P=0.240). The need for
      revision was significantly greater in the non-IPOP group (IPOP 5.4% vs. non-IPOP
      27.6%; P=0.013). The time from surgery to placement of the preparatory prosthesis
      was 51 days in the IPOP group. CONCLUSIONS: Patients undergoing IPOP have similar
      perioperative systemic and wound complication rates compared to those patients
      undergoing conventional below-knee amputation, but are less likely to require
      surgical revision. The use of IPOP allows for early ambulation and
      rehabilitation, which may be of psychological benefit and may decrease the
      sequelae of prolonged immobilization. IPOP application should be considered for
      all appropriate candidates requiring below-knee amputation.

PMID- 23972637
TI  - Role of saphenofemoral junction ligation combined with ultrasound-guided foam
      sclerotherapy in patients with venous ulcers.

PMID- 23972638
TI  - Reversed saphenous bypass for hepatic artery pseudoaneurysm after liver
      transplantation.
AB  - BACKGROUND: Hepatic artery pseudoaneurysm (HAP) is found in 1-2% of liver
      transplantation (LT) patients. The mortality associated with pseudoaneurysm
      formation after orthotopic LT is reported to be as high as 75%. Because of the
      rarity of complications, particularly when considered individually, much of the
      direction for the management of complications is anecdotal. This article
      discusses the presentation, etiology, types, treatment indications, and vascular
      procedures used to manage complications with LT. METHODS: Between January 2004
      and December 2011, 464 LTs were performed at our institution. Of these, 9 (1.9%)
      consecutive patients underwent surgical treatment of HAP (8 men and 1 woman;
      median age, 58.4 years [range, 46-67 years]). Four patients underwent
      transarterial chemoembolization before LT for hepatocellular carcinoma. In all
      cases, revascularization with a reversed autologous saphenous vein bypass was
      performed. RESULTS: Four patients had ruptured pseudoaneurysms, and the others
      were diagnosed as having asymptomatic pseudoaneurysms during the follow-up
      period. The median delay between LT and the diagnosis of HAP was 39.6 days
      (range, 22-92 days). All were anatomically extrahepatic. The median diameter was
      15.3 mm (range, 9-30 mm). Four patients had a T-tube. In 6 cases, biliary leakage
      was associated with the LT and, in the remaining 3, mycosis was recorded. After
      surgery, 1 patient underwent retransplantation because of ischemic cholangitis.
      Five years later, 5 patients had normal arterial anatomy, and the other 3
      patients had stenosis that was successfully treated by stents. All of the
      patients had normal liver function at follow-up. One patient died 16 months later
      because of a heart attack. CONCLUSIONS: HAP with massive intraperitoneal bleeding
      is a rare but serious life-threatening complication when it occurs after LT. The
      majority of HAP cases are associated with bile leakage and mycosis; therefore,
      surgery must be the treatment of choice. Our conclusions support surgical
      revascularization with reversed saphenous grafts as a feasible and efficient
      treatment in cases of HAP.

PMID- 23972639
TI  - Abdominal aortic aneurysmal and endovascular device infection with iliopsoas
      abscess caused by Mycobacterium bovis as a complication of intravesical bacillus
      Calmette-Guerin therapy.
AB  - Vascular complications after the intravesical instillation of Bacillus Calmette
      Guerin (BCG) therapy are extremely rare. We experienced a case of abdominal
      aortic aneurysmal infection excluded by a stent graft with an iliopsoas abscess
      after intravesical instillation of BCG therapy that required reoperation. Five
      years ago, an 81-year-old man was diagnosed with transitional cell carcinoma of
      the bladder. After transurethral resection of the bladder tumor and intravesical
      BCG therapy, a radical cystectomy was performed. Twenty-four months after
      intravesical BCG therapy, follow-up an abdominal computed tomographic (CT) scan
      revealed an aortic abdominal aneurysm. Endovascular aneurysm repair was
      performed, and the aneurysm was excluded postoperatively. Thirty months after the
      endovascular aneurysm repair (and 54 months after intravesical BCG therapy), a
      follow-up abdominal CT revealed a low-density area in the right iliopsoas muscle
      that formed a fistula to the excluded aneurysm. We performed CT-guided iliopsoas
      abscess drainage and collected yellow pus. Polymerase chain reaction analysis
      revealed that the pus was positive for Mycobacterium tuberculosis complex. The
      patient was diagnosed with abdominal aortic aneurysmal infection associated with
      iliopsoas abscess caused by Mycobacterium bovis, and surgery was performed. We
      performed an extra-anatomical bypass and removed the stent graft with
      debridement. When the aneurysmal wall was incised and resected, yellow pus
      surrounded the stent graft. In addition, a large fistula was present between the
      right posterolateral aortic aneurysmal wall and the iliopsoas abscess cavity.
      After the operation, the histopathological examination of excised abdominal
      aortic aneurysmal wall tissue revealed an epithelioid granuloma with caseous
      necrosis involving multinucleated giant cells, indicating M tuberculosis complex
      infection. Although the intravesical instillation of BCG therapy is considered
      safe, complications resulting from vascular infections can arise in extremely
      rare cases. The complication described in this case report emphasizes the need to
      cautiously select treatment for a mycotic aortic aneurysm after intravesical
      instillation of BCG therapy. 

PMID- 23972640
TI  - Marjolin's ulcer in a patient with chronic venous stasis.
AB  - Marjolin's ulcer is an aggressive form of squamous cell carcinoma that develops
      over time from chronic wounds and scars, including burns and chronic venous
      stasis ulcers. The incidence of malignant transformation is low, resulting in a
      delay in diagnosis and increased morbidity and mortality in these patients. We
      report a case of Marjolin's ulcer that was incidentally found after limb
      amputation for chronic venous stasis ulcer along with a comprehensive literature
      review on the etiology, diagnosis, and treatment of this disease. 

PMID- 23972641
TI  - Evaluation method for the cytotoxicity of cigarette smoke by in vitro whole smoke
      exposure.
AB  - An in vitro whole smoke (WS) exposure method was established to evaluate the
      toxicological effects of fresh cigarette smoke using the VITROCELL((r)) system
      associated with the neutral red uptake (NRU) cytotoxicity assay. The
      VITROCELL((r)) system is a newly representative culture and exposure system for
      in vitro studies of gases or complex mixtures. The impacts of two factors on
      cytotoxicity measurements of cigarette smoke were investigated using this WS
      exposure system. The factors include synthetic air exposure and optimal time to
      perform the NRU assay after smoke exposure. Results showed that synthetic air
      exposure used in the system did not significantly alter cell survival; 24h after
      smoke exposure appeared to be an optimal time-point to assess the cytotoxicity of
      cigarette smoke. A clear dose-response relationship between smoke exposure and
      cell viability was demonstrated using this system, and the evaluation method was
      sensitive to distinguish the differences in smoke-induced cytotoxic effects from
      different cigarettes. In addition, we tried converting the values of EC50 from WS
      exposure testing into the values in unit used in total particulate matter (TPM)
      testing for a purpose of comparison, and the data indicate that the cytotoxicity
      of smoke measured by WS exposure is greater than that measured by TPM exposure.

PMID- 23972642
TI  - Reference ranges for regional cerebral tissue oxygen saturation and fractional
      oxygen extraction in neonates during immediate transition after birth.
AB  - OBJECTIVE: To define reference ranges for regional cerebral tissue oxygen
      saturation (crSO2) and regional cerebral fractional tissue oxygen extraction
      (cFTOE) during the first 15 minutes after birth in neonates requiring no medical
      support. STUDY DESIGN: The crSO2 was measured using near infrared spectroscopy
      (Invos 5100 cerebral/somatic oximeter monitor; Somanetics Corp, Troy, Michigan)
      during the first 15 minutes after birth for term and preterm neonates. The near
      infrared spectroscopy sensor was placed on the left forehead. Peripheral oxygen
      saturation and heart rate were continuously measured by pulse oximetry, and cFTOE
      was calculated. Neonates were excluded if they required any medical support.
      RESULTS: A total of 381 neonates were included: 82 term neonates after vaginal
      delivery, 272 term neonates after cesarean delivery, and 27 preterm neonates
      after cesarean delivery. In all neonates, median (10th-90th percentiles) crSO2
      was 41% (23-64) at 2 minutes, 68% (45-85) at 5 minutes, 79% (65-90) at 10
      minutes, and 77% (63-89) at 15 minutes of age. In all neonates, median (10th-90th
      percentiles) cFTOE was 33% (11-70) at 2 minutes, 21% (6-45) at 5 minutes, 15% (5
      31) at 10 minutes, and 18% (7-34) at 15 minutes of age. CONCLUSION: We report
      reference ranges of crSO2 and cFTOE in neonates requiring no medical support
      during transition immediately after birth. The use of cerebral oxygenation
      monitoring and use of these reference ranges in neonates during transition may
      help to guide oxygen delivery and avoid cerebral hypo-oxygenation and
      hyperoxygenation.

PMID- 23972643
TI  - Serum thyrotropin concentration in children with isolated thyroid nodules.
AB  - OBJECTIVE: To investigate the correlation between serum thyroid-stimulating
      hormone (TSH) concentration and nodule nature in pediatric patients with thyroid
      nodules, with the aim of identifying a marker able to differentiate benign and
      malignant nodules. STUDY DESIGN: This was a retrospective analysis of serum TSH
      concentrations in a multicentric case series of 125 pediatric patients with
      benign and malignant thyroid nodules. RESULTS: Of the 125 patients, 99 had benign
      thyroid nodules and 26 had differentiated thyroid cancer (24 papillary and 2
      follicular). Final diagnosis was based on surgery in 57 cases and on a benign
      cytology plus clinical follow-up in 68 cases. Serum TSH concentration was
      significantly higher in patients with thyroid cancer compared with those with
      benign nodules (3.23 +/- 1.59 mU/L vs 1.64 +/- 0.99 mU/L; P < .001). Binary
      logistic regression analysis revealed that serum TSH was the sole predictor of
      malignancy (P < .001). Dividing the patient cohort into 5 groups based on serum
      TSH quintiles (TSH cutoffs 0.40, 1.00, 1.50, 1.80, and 2.80 mU/L), we observed
      that cancer prevalence increased in parallel with serum TSH (P < .001), with
      respective rates of 0%, 4%, 16%, 32%, and 52% in the 5 quintile groups.
      CONCLUSION: Because cases with malignant nodules are most likely seen in the
      upper normal serum TSH range (ie, >2.8 mU/L), serum TSH concentration can serve
      as a predictor of thyroid cancer in pediatric patients with thyroid nodules and
      can inform the decision of when to submit patients to further investigation by
      cytology.

PMID- 23972644
TI  - Evaluation of early childhood social-communication difficulties in children born
      preterm using the Quantitative Checklist for Autism in Toddlers.
AB  - OBJECTIVES: To characterize early childhood social-communication skills and
      autistic traits in children born very preterm using the Quantitative Checklist
      for Autism in Toddlers (Q-CHAT) and explore neonatal and sociodemographic factors
      associated with Q-CHAT scores. STUDY DESIGN: Parents of children born before 30
      weeks gestation and enrolled in a study evaluating routinely collected
      neurodevelopmental data between the post-menstrual ages of 20 and 28 months were
      invited to complete the Q-CHAT questionnaire. Children with severe neurosensory
      disabilities and cerebral palsy were excluded. Participants received
      neurodevelopmental assessments using the Bayley Scales of Infant and Toddler
      Development, 3rd edition (Bayley-III). Q-CHAT scores of this preterm cohort were
      compared with published general population scores. The association between Bayley
      III cognitive and language scores and neonatal and sociodemographic factors with
      Q-CHAT scores were examined. RESULTS: Q-CHAT questionnaires were completed from
      141 participants. At a mean post-menstrual age of 24 months, the Q-CHAT scores of
      the preterm cohort (mean 33.7, SD 8.3) were significantly higher than published
      general population scores (mean 26.7; SD 7.8), indicating greater social
      communication difficulty and autistic behavior. Preterm children received higher
      scores, particularly in the categories of restricted, repetitive, stereotyped
      behavior, communication, and sensory abnormalities. Lower Bayley-III language
      scores and non-white ethnicity were associated with higher Q-CHAT scores.
      CONCLUSIONS: Preterm children display greater social-communication difficulty and
      autistic behavior than the general population in early childhood as assessed by
      the Q-CHAT. The implications for longer-term outcome will be important to assess.

PMID- 23972645
TI  - Favorable acceptance of mini-tablets compared with syrup: a randomized controlled
      trial in infants and preschool children.
AB  - OBJECTIVE: To evaluate acceptability of 2 mm solid dosage forms (mini-tablets) as
      an alternative administration modality in young children in comparison with
      syrup. STUDY DESIGN: Three hundred six pediatric in- and outpatients aged 6
      months-5 years (51 in each of 6 age groups) were recruited. An open, randomized
      cross-over study was conducted to compare acceptability and capability to swallow
      2 mm uncoated or coated mini-tablets vs 3 mL syrup. RESULTS: In the overall
      patient population of 306 children, the acceptability of uncoated mini-tablets
      was superior to syrup (difference in proportions 14.8%, 95% CI 10.2-19.4; P <
      .0001). In line with this finding, the level of capability to swallow was higher
      for uncoated mini-tablets compared with syrup as well (difference in proportions
      12.3%, 95% CI 5.4-19.3; P = .0008). All 3 pharmaceutical formulations were well
      tolerated, and none of the 306 children inhaled or coughed because of the syrup
      or the uncoated mini-tablet; only 2 of the 306 children (both in age group 0.5-1
      year) coughed because of the coated mini-tablet, in both cases without clinical
      relevance. CONCLUSIONS: Mini-tablets are a valuable alternative to syrup for
      children 6 months-6 years of age and are more acceptable compared with liquid
      formulation. Regulatory bodies such as Food and Drug Administration and European
      Medicine Agency are encouraged to take our data into account for guideline
      updates and future drug approval processes.

PMID- 23972646
TI  - Attention problems in childhood and adult substance use.
AB  - OBJECTIVE: To assess the link between childhood attention problems (AP) and
      substance use 18 years later. STUDY DESIGN: This cohort study was conducted in a
      community sample of 1103 French youths followed from 1991 to 2009. Exposures and
      covariates were childhood behavioral problems (based on parental report at
      baseline), early substance use, school difficulties, and family adversity.
      Outcome measures were regular tobacco smoking, alcohol problems, problematic
      cannabis use, and lifetime cocaine use (based on youth reports at follow-up).
      RESULTS: Individuals with high levels of childhood AP had higher rates of
      substance use (regular tobacco smoking, alcohol problems, problematic cannabis
      use, and lifetime cocaine use). However, when taking into account other childhood
      behavioral problems, early substance use, school difficulties, and family
      adversity, childhood AP were related only to regular tobacco smoking and lifetime
      cocaine use. Early cannabis exposure was the strongest risk factor for all
      substance use problems. CONCLUSION: This longitudinal community-based study shows
      that, except for tobacco and cocaine, the association between childhood AP and
      substance use is confounded by a range of early risk factors. Early cannabis
      exposure plays a central role in later substance use.

PMID- 23972647
TI  - Is timing to delivery of treatment a reliable measure of quality of care for
      patients with colorectal adenocarcinoma?
AB  - BACKGROUND: Among patients with colorectal adenocarcinoma, patient race has been
      associated with differences in colorectal cancer survival. Survival disparities
      between ethnic groups may be related to treatment delays, treating hospital, or
      other patient factors. We hypothesized that prolonged interval to delivery of
      cancer therapy negatively impacts survival. STUDY DESIGN: We designed a
      retrospective cohort study using tumor registry and clinical database information
      from two academically affiliated hospitals. We examined factors associated with
      interval to treatment and associations between interval and overall survival.
      RESULTS: Among 592 patients treated by a cohort of physicians, we found no
      differences in cancer stage related to race or treating hospital. Interval to
      treatment differed between different hospitals (29 vs. 16 days; P < .0001); yet,
      there were no differences in overall survival related to treatment interval,
      treating hospital, race, or insurance status. Tumor grade and tumor stage were
      associated with decreased overall survival. CONCLUSION: Differences exist related
      to the timing of definitive care for patients in this series; however, these
      differences do not translate directly into differences in overall survival. We
      must deliver quality health care in an efficient and timely manner; however, the
      metric of interval to treatment may not measure reliably the quality of care
      received.

PMID- 23972648
TI  - MeSS: A novel prognostic scale specific for pediatric well-differentiated thyroid
      cancer: a population-based, SEER outcomes study.
AB  - BACKGROUND: High-risk prognostic factors for adults with well-differentiated
      thyroid cancer (WDTC) have been well established, but the same is not true for
      pediatric patients. This study sought to determine whether validated adult
      prognostic systems are applicable to pediatric patients and to develop a novel
      prognostic scale that may better reflect outcomes in pediatric subgroups.
      METHODS: We queried 62,007 cases of WDTC from the Surveillance, Epidemiology, and
      End Results (SEER) database (1973-2009) to identify 895 patients <20 years of age
      with WDTC. Data abstracted included age, gender, race, histology type, primary
      tumor size, cancer stage, and mortality. Odds ratio and 95% confidence intervals
      were set and data were analyzed with SAS version 9.2. RESULTS: Among 895
      pediatric WDTC patients, the overall cause-specific mortality was 0.8%. The
      presence of distant metastasis was associated with the worst prognosis (P =
      .0045) followed by larger primary tumor size (P = .0135) and male gender (P =
      .0162). When classified into low-, moderate-, and high-risk categories according
      to the distant metastasis (Me), larger primary tumor size (S), and male sex (S)
      (MeSS) algorithm, mortality rates were 0%, 2.7%, and 23%, respectively.
      CONCLUSION: Commonly used prognostic indices for WDTC in adults do not reliably
      predict poor outcomes among pediatric patients. Rather, a system based on MeSS is
      more applicable to pediatric patients. Patients who exhibit a high MeSS score
      have a significantly worse overall survival than those who do not express any
      MeSS characteristics.

PMID- 23972649
TI  - Altered expression and activation of mitogen-activated protein kinases in
      diabetic heart during cardioplegic arrest and cardiopulmonary bypass.
AB  - BACKGROUND: We investigated whether mitogen-activated protein kinases (MAPKs) are
      changed in the hearts of patients with diabetes after cardioplegia and
      cardiopulmonary bypass (CP/CPB) operations. METHODS: Biopsies from the right
      atrial appendage were harvested pre- and post-CP/CPB from nondiabetic (ND)
      patients (n = 8, hemoglobin A1c (HbA1c) = 5.4 +/- 0.12); patients with controlled
      diabetes (CDM) (n = 8, HbA1c = 6.5 +/- 0.15); and patients with uncontrolled
      diabetes (UDM) (n = 8, HbA1c = 9.6 +/- 0.3) undergoing coronary artery bypass
      grafting. The expression and/or activation of the p38-MAPK, ERK1/2, JNK, and MKP
      1 in the right-atrial tissues were analyzed by Western blotting. The vasomotor
      function of coronary arterioles was measured by videomicroscopy. RESULTS: The
      post-CP/CPB levels of total p38-MAPK were decreased in the 3 groups as compared
      with their pre-CP/CPB levels (P < .05). There were increases in phospho-p38-MAPK,
      phospho-ERK1/2, and MKP-1 in UDM patients as compared with ND and CDM patients at
      baseline (P < .05). Compared to pre-CP/CPB, the post-CP/CPB levels of phospho-p38
      MAPK decreased in the UDM group but were unaltered in the ND and CDM groups;
      however, the post-CP/CPB levels of phospho-p38-MAPK still remained greater than
      the post-CP/CPB levels of the other 2 groups. Post-CP/CPB levels of phospho
      ERK1/2 were increased in the ND and CDM groups but were decreased in the UDM
      group compared to their pre-CP/CPB levels, respectively (P < .05). There were no
      significant differences in phospho-JNK in 3 groups at baseline. Post-CP/CPB
      levels of phospho-JNK, however, were increased in the 3 groups and were more
      pronounced in the myocardium of the UDM group (P < .05). After CP/CPB, the
      protein levels of MKP-1 were unchanged in the 3 groups when compared with their
      pre-CP/CPB levels. Post-CP/CPB levels of MKP-1, however, remained greater in the
      UDM group than in the ND and CDM groups. The post-CP/CPB contractile responses to
      the thromboxane A2 analog U46619 were significantly impaired in all 3 groups
      compared with pre-CP/CPB contractile responses. These impairments were more
      pronounced in the UDM group. CONCLUSION: Uncontrolled diabetes is associated with
      changes in expression of and activation of MAPKs and vasomotor dysfunction in the
      setting of CP/CPB.

PMID- 23972650
TI  - Age, poverty, acculturation, and gastric cancer.
AB  - BACKGROUND: Gastric cancer is an aggressive disease, and overall changes in
      incidence rates have been noted. There are conflicting data on whether young
      patients have worse outcomes than older patients; the roles of tumor biology and
      access to care are critical to answering this question. Our objectives were to
      explore how gastric cancer rates, receipt of care, and outcomes are affected by
      age, poverty, and acculturation. METHODS: A total of 42,187 patients were
      identified from the 1980-2009 Surveillance, Epidemiology, and End Results
      registry. We compared trends in incidence rates between patients <40, 40-64, and
      >=65 years using ordinary least-squares regression. Separate multivariate
      regression models were used to evaluate the impact of age, poverty, and
      acculturation on receipt of cancer-directed therapy and hazard of mortality.
      RESULTS: Patients <40 years had stable incidence rates over the 3-decade period
      compared with decreases for patients 40-64 and >=65 years. They are also more
      likely to present with aggressive, advanced disease (P < .0001 for both). On
      unadjusted and adjusted analyses, patients <40 years were more likely to receive
      cancer-directed therapies and have better survival than those >=65 years.
      Residing in high poverty areas was associated with not receiving appropriate
      cancer-directed therapy; the adjusted hazard ratio of mortality for surgically
      resected patients was, however, not affected by poverty. Residing in high
      immigration areas was associated with a low hazard ratio (HR, 0.74; 95%
      confidence interval [CI], 0.7-0.79) of mortality. Foreign-born patients also had
      a low hazard ratio (HR, 0.87; 95% CI, 0.83-0.91) of mortality. CONCLUSION:
      Although trends in incidence rates for patients <40 years remain unchanged and
      their disease is aggressive and advanced at presentation, they do not experience
      disparities in gastric cancer-directed therapies and survival after resection.
      For patients residing in impoverished areas or high immigration communities,
      operative resection and adjustment for appropriate aftercare is associated with
      comparable or better survival when compared with those living in low poverty or
      low immigration areas. Disparities remain in receipt of appropriate cancer
      directed therapies, and future efforts should focus on decreasing structural
      variations in care and unconscious biases regarding patients from these
      vulnerable communities.

PMID- 23972651
TI  - Efficacy of localization studies and intraoperative parathormone monitoring in
      the surgical management of hyperfunctioning ectopic parathyroid glands.
AB  - BACKGROUND: Hyperfunctioning ectopic glands remain an operative challenge in
      patients with sporadic primary hyperparathyroidism. This study examines the
      incidence of ectopic glands and the utility of sestamibi scans (MIBI), surgeon
      performed ultrasonography, and intraoperative parathormone monitoring in such
      patients undergoing parathyroidectomy. METHODS: We conducted a retrospective
      analysis of prospectively collected data from patients who underwent
      parathyroidectomy from 1980 to 2011 for sporadic primary hyperparathyroidism at a
      single institution. Demographics, localizing imaging studies, intraoperative
      parathyroid monitoring dynamics, and surgical outcome for patients with
      hyperfunctioning ectopic parathyroid glands were studied. RESULTS: Among 1,195
      patients who underwent parathyroidectomy for sporadic primary
      hyperparathyroidism, 120 patients (10%) had hyperfunctioning ectopic glands,
      which were localized to the neck (n = 66) and mediastinum (n = 54). MIBI had a
      sensitivity of 85%, specificity of 97%, and positive predictive value (PPV) of
      91% for ectopic glands in the neck, whereas in the mediastinum there was a
      sensitivity of 88%, specificity of 95%, and PPV of 86%. Surgeon-performed
      ultrasonography had a sensitivity of 81%, specificity of 98%, and PPV of 95% for
      neck ectopic glands. The overall accuracy of surgeon-performed ultrasonography,
      MIBI, and intraoperative parathyroid monitoring in the neck or mediastinum was
      93%. Overall, operative success was 93% with a multiglandular disease rate of 5%.
      CONCLUSION: A high operative success rate for hyperfunctioning ectopic glands can
      be achieved using localization studies and intraoperative parathyroid monitoring.
      Nevertheless, surgeon judgment remains paramount in the operative direction of
      this patient population.

PMID- 23972652
TI  - Socioeconomic disparity in inpatient mortality after traumatic injury in adults.
AB  - BACKGROUND: Prior studies have demonstrated that race and insurance status
      predict inpatient trauma mortality, but have been limited by their inability to
      adjust for direct measures of socioeconomic status (SES) and comorbidities. Our
      study aimed to identify whether a relationship exists between SES and inpatient
      trauma mortality after adjusting for known confounders. METHODS: Trauma patients
      aged 18-65 years with an Injury Severity Scores (ISS) of >=9 were identified
      using the 2003-2009 Nationwide Inpatient Sample. Median household income (MHI) by
      zip code, available by quartiles, was used to measure SES. Multiple logistic
      regression analyses were performed to determine odds of inpatient mortality by
      MHI quartile, adjusting for ISS, type of injury, comorbidities, and patient
      demographics. RESULTS: In all, 267,621 patients met inclusion criteria. Patients
      in lower wealth quartiles had significantly greater unadjusted inpatient
      mortality compared with the wealthiest quartile. Adjusted odds of death were also
      higher compared with the wealthiest quartile for Q1 (odds ratio [OR], 1.13; 95%
      confidence interval [CI], 1.06-1.20), Q2 (OR, 1.09; 95% CI, 1.02-1.17), and Q3
      (OR, 1.11; 95% CI, 1.04-1.19). CONCLUSION: MHI predicts inpatient mortality after
      adult trauma, even after adjusting for race, insurance status, and comorbidities.
      Efforts to mitigate trauma disparities should address SES as an independent
      predictor of outcomes.

PMID- 23972653
TI  - Inhibition of nuclear factor-kappaB enhances the antitumor effect of tumor
      necrosis factor-alpha gene therapy for hepatocellular carcinoma in mice.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is often resistant to chemotherapy.
      Gene therapy using an adenoviral vector-expressing tumor necrosis factor (TNF)
      alpha is a new therapeutic approach for chemoresistant malignancies. The efficacy
      of TNF-alpha, however, is limited, because it leads to the activation of nuclear
      factor (NF)-kappaB. We hypothesized that the NF-kappaB inhibitor nafamostat
      mesilate would enhance the antitumor effect of adenovirus vector-mediated TNF
      alpha gene therapy for HCC. METHODS: In vitro, we assessed the inhibitory effect
      of nafamostat mesilate on TNF-alpha-induced NF-kappaB activation and enhanced
      apoptosis in human HCC cell lines (Huh-7 and Hep3B). In vivo, we established a
      xenograft HCC model in mice by subcutaneous injection of Huh-7 and Hep3B cells.
      The animals received intraperitoneal (IP) injections of nafamostat mesilate 3
      times a week (nafamostat mesilate group), intratumoral (IT) injections of the
      human TNF-alpha-expressing adenoviral vector (AxCAhTNF-alpha) once a week (TNF
      alpha group), IT injections of AxCAhTNF-alpha once a week, or IP injections of
      nafamostat mesilate 3 times a week (combination group). RESULTS: In the
      combination group, TNF-alpha-induced NF-kappaB activation was inhibited and TNF
      alpha-induced apoptosis was enhanced in comparison with the other groups both in
      vitro and in vivo. In the combination group, tumor growth was significantly
      slower and the apoptotic cell numbers were significantly greater than those of
      the TNF-alpha group. CONCLUSION: Inhibition of NF-kappaB by nafamostat mesilate
      enhances the antitumor effect of adenoviral vector-mediated TNF-alpha gene
      therapy for HCC in mice.

PMID- 23972654
TI  - Increased complications after appendectomy in patients with cerebral palsy: are
      special needs patients at risk for disparities in outcomes?
AB  - BACKGROUND: Cerebral palsy (CP) is a nonprogressive neurologic disorder.
      Anecdotal evidence suggests there are worse outcomes in this population after
      common operative procedures like appendectomy. This study aims to classify
      whether there are relevant disparities in postoperative outcomes in CP versus non
      CP patients after open or laparoscopic appendectomy. METHODS: Hospital discharge
      data from the 2003-2009 weighted Nationwide Inpatient Sample were used.
      Unadjusted and adjusted multiple logistic regression were used to assess
      postoperative complications, as well as inpatient mortality, average duration of
      hospital stay, and cost. RESULTS: Approximately 1,250 patients with CP met the
      inclusion criteria. After adjusted analysis, CP patients displayed significantly
      greater odds of the following postoperative complications: Sepsis/organ failure,
      operation-related infection, pneumonia, urinary tract infection, and acute
      respiratory distress syndrome. Patients with CP also had a greater cost and in
      hospital stay after appendectomy. CONCLUSION: Patients with CP have greater
      adjusted odds of complications after open or laparoscopic appendectomy. The
      mechanisms that led to these disparities need to be studied and may include
      difficulties in patient assessment and communication. Additional education of
      healthcare providers to improve recognition of symptoms and care for patients
      with disabilities may be more immediately helpful in decreasing disparities in
      outcomes.

PMID- 23972655
TI  - Irreversible electroporation facilitates gene transfer of a GM-CSF plasmid with a
      local and systemic response.
AB  - BACKGROUND: Electroporation uses an electric field to induce pores in the cell
      membrane that can transfer macromolecules into target cells. Modulation of
      electrical parameters leads to irreversible electroporation (IRE), which is being
      developed for tissue ablation. We sought to evaluate whether the application of
      IRE may induce a lesser electric field in the periphery where reversible
      electroporation may occur, facilitating gene transfer of a granulocyte macrophage
      colony-stimulating factor (GM-CSF) plasmid to produce its biologic response.
      METHODS: Yorkshire pigs underwent laparotomy, and IRE of the liver was performed
      during hepatic arterial infusion of 1 or 7 mg of a naked human GM-CSF plasmid.
      The serum, liver, lymph nodes, and bone marrow were harvested for analysis.
      RESULTS: Human GM-CSF level rose from undetectable to 131 pg/mL in the serum at
      24 hours after IRE and plasmid infusion. The liver demonstrated an ablation zone
      surrounded by an immune infiltrate that had greater macrophage intensity than
      when treated with IRE or plasmid infusion alone. This dominance of macrophages
      was dose dependent. Distant effects of GM-CSF were found in the bone marrow,
      where proliferating myeloid cells increased from 14% to 25%. CONCLUSION: IRE
      facilitated gene transfer of the GM-CSF plasmid and brought about a local and
      systemic biologic response. This technique holds potential for tumor eradication
      and immunotherapy of residual cancer.

PMID- 23972656
TI  - An assessment of the necessity of transfusion during pancreatoduodenectomy.
AB  - INTRODUCTION: Perioperative transfusion of packed red blood cells (PRBC) has been
      associated with negative side effects. We hypothesized that a majority of
      transfusions in our series of patients who underwent pancreaticoduodenectomy (PD)
      were unnecessary. A retrospective analysis was performed to determine whether
      transfusions were indicated based on pre-determined criteria, and the impact of
      perioperative transfusions on postoperative outcomes was assessed. METHODS: Our
      prospectively maintained database was queried for patients who underwent PD
      between 2004 and 2011. 200 patients were divided into Cohort 1 (no transfusion)
      and Cohort 2 (transfusion). Rates of various graded 90-day postoperative
      complications were compared. Categorical values were compared according to the
      Common Terminology Criteria for Adverse Events. All cases involving
      intraoperative blood transfusion were reviewed for associated blood loss,
      intraoperative vital signs, urine output, hemoglobin values, and presence or
      absence of EKG changes to determine whether the transfusion was indicated based
      on these criteria. RESULTS: There were 164 patients (82%) in Cohort 1 (no
      transfusion) and 36 patients (18%) in Cohort 2 (transfused). Both groups had
      similar demographics. Patients in Cohort 2 had lesser median preoperative values
      of hemoglobin (12.3 vs 13.1, P = .002), a greater incidence of vein resection
      (33% vs. 16%, P = .021), longer operative times (518 vs 440 minutes, P < .0001),
      a greater estimated blood loss (850 vs. 300 mL, P < .001), and greater
      intraoperative fluid resuscitation (6,550 vs. 5,300 mL, P = .002). Ninety-day
      mortality was similar between the 2 groups (3% vs 1%, P = .328). Patients in
      Cohort 2 (transfused) had increased rates of delayed gastric emptying (36% vs.
      20%, P = .031), wound infection (28% vs. 7%, P = .031), pulmonary complications
      (6% vs. 0%, P = .032), and urinary retention (6% vs. 0%, P = .032). A greater
      incidence of any complication of grade II severity (67% vs. 35%, P = .0005) or
      grade III severity (36% vs. 17%, P = .010) was also noted in Cohort 2. Of the 33
      intraoperative transfusions, 15 (46%) did not meet any of the predetermined
      criteria: intraoperative hypotension (<90/60 mmHg), tachycardia (>110 beats per
      minute), low urine output (<10 mL/hour), decreased oxygen saturation (<95%),
      excessive blood loss (>1,000 mL), EKG changes, and low hemoglobin (<7.0 g/dL).
      CONCLUSION: Perioperative transfusions among patients with PD were associated
      with increased rates of various postoperative complications. A substantive
      portion (~46%) of perioperative transfusions in this patient population did not
      meet predetermined criteria, indicating a potential opportunity for improved
      blood product use. Further prospective studies are required to determine whether
      the implementation of these criteria may a positive impact on perioperative
      outcomes.

PMID- 23972657
TI  - Clinical significance of CXCL-8/CXCR-2 network in esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: CXCL-8, known as proinflammatory cytokine interleukin (IL)-8, and its
      receptor, CXCR-2, are expressed in various cancer cells. CXCL-8/CXCR-2 network is
      believed to be involved in angiogenesis, growth, and invasion of tumor cells. To
      date, the clinical significance of CXCL-8/CXCR-2 network in esophageal squamous
      cell carcinoma (ESCC) remains unclear. Here, we investigated the role of CXCL-
      8/CXCR-2 network in ESCC. METHODS: The subjects included 78 patients with primary
      ESCC. We examined CXCL-8 and CXCR-2 expression in surgically resected specimens
      using immunohistochemistry. The association between CXCL-8/CXCR-2 expression and
      level of preoperative serum cytokines, C-reactive protein (CRP), coagulation
      factors, clinicopathologic background factors, and survival of ESCC patients was
      assessed. RESULTS: Thirty-seven (47%) and 36 (46%) patients were positive for
      CXCL-8 and CXCR-2 expression, respectively. Both CXCL-8 and CXCR-2 were expressed
      in 26 patients (33%). We compared the results of these 26 patients [CXCL
      8(+)/CXCR-2(+) group] with those of the other group (n = 52). The depth of
      invasion (pT factor; P < .001), lymph node metastasis (pN factor; P = .001),
      pathologic stage (P < .001), lymphatic invasion (P = .010), and venous invasion
      (P = .001) were significantly more advanced in the CXCL-8(+)/CXCR-2(+) group
      compared with the other group. Preoperative IL-6, IL-8, CRP, fibrin/fibrinogen
      degradation product, and fibrinogen levels in the CXCL-8(+)/CXCR-2(+) group were
      also significantly higher than those in the other group (P = .046, .009, .029,
      .010, and <.001, respectively). The CXCL-8(+)/CXCR-2(+) group also showed a
      significantly lower recurrence-free survival (RFS; P < .001) and disease-specific
      survival (P = .008). As per Cox's hazards model, CXCL-8/CXCR-2 expression (hazard
      ratio, 2.89; P = .008) was independent predictive factor for RFS. CONCLUSION:
      Increased expression of both CXCL-8 and CXCR-2 correlated with tumor progression,
      metastasis, higher preoperative levels of proinflammatory cytokines, CRP,
      activation of exogenous coagulation factors, and poor prognosis in ESCC patients.
      These results indicate that overexpression of both CXCL-8 and CXCR-2 may be a
      useful marker for predicting the outcome in ESCC patients, and more important,
      has potential in becoming a critical diagnostic marker for selection of
      appropriate treatments.

PMID- 23972658
TI  - Poor outcome in bacterial peritonitis is associated with dysregulated microRNAs
      and an increased inflammatory response.
AB  - BACKGROUND: Peritonitis is a common cause of surgical sepsis. The failure of the
      host to mount an appropriate immune response contributes to persistence of the
      infection. We investigated the role microRNAs may play in this failed immune
      response. METHODS: Klebsiella pneumoniae was injected intraperitoneally in mice.
      Weight loss was used to predict clinical outcome. Peritoneal exudate cells (PECs)
      and supernatant were collected. RNA from PECs was run on screening microRNA array
      cards to determine gene expression, and validated by single assay analysis.
      Cytokine levels in supernatant were assayed by enzyme-linked immunosorbent assay.
      RESULTS: Despite similar bacterial levels, PEC counts were higher in the
      predicted death group. The predicted deaths had higher levels of proinflammatory
      tumor necrosis factor-alpha/IL-6 and significantly lower levels of interleukin
      10. MiR-221 was up-regulated in both the predicted death and predicted survivor
      groups. Five miRNAs were up-regulated in the predicted survivor group compared
      with normal controls. CONCLUSION: Higher PEC counts and proinflammatory cytokines
      in the predicted death group indicates an exaggerated inflammatory response, with
      lower IL-10 levels despite similar bacterial counts. There were two dysregulated
      miRNAs with transcriptional targets that may explain our results. A more balanced
      immune response with an appropriate counter inflammatory response may be
      important for improving survival.

PMID- 23972659
TI  - Association of preoperative symptoms of gastric outlet obstruction with delayed
      gastric emptying after pancreatoduodenectomy.
AB  - BACKGROUND: Delayed gastric emptying (DGE) is among the most common complications
      after pancreatoduodenectomy (PD) and might demand postoperative nutritional
      support. The aim of this study was to investigate the association between
      preoperative symptoms of gastric outlet obstruction and DGE after PD in an
      attempt to identify patients in whom placement of a feeding tube at time of
      operation might be beneficial. METHODS: We analyzed a consecutive series of 401
      patients undergoing PD from a prospective database. Preoperative symptoms of
      nausea, vomiting, loss of appetite, weight loss, postprandial complaints, and
      dysphagia were retrospectively determined. Primary outcome was clinically
      relevant DGE according to the International Study Group of Pancreatic Surgery
      classification and the necessity of postoperative insertion of a nasojejunal
      feeding tube. RESULTS: The incidence of clinically relevant DGE was 33.2%
      (133/401 patients). A nasojejunal feeding tube was inserted in 119 patients
      (29.7%). Patients having >=2 symptoms of gastric outlet obstruction except weight
      loss (50 patients; 12.5%), were at a greater risk of developing both DGE (21.1%
      vs 8.2%; P < .001) and the need for insertion of a feeding tube (21.8% vs 8.5%; P
      < .001). In multivariable logistic regression analysis, the presence of >=2
      symptoms of gastric outlet obstruction other than weight loss remained a
      significant predictor of DGE (odds ratio [OR], 3.1; 95% confidence interval [CI],
      1.7-5.8) and the need for insertion of a nasojejunal feeding tube (OR, 3.1; 95%
      CI, 1.7-5.7). CONCLUSION: The preoperative presence of >=2 symptoms of gastric
      outlet obstruction is a significant predictor of postoperative DGE after PD. By
      applying this risk factor, patients in whom placement of a feeding tube during
      surgery should be considered can be identified.

PMID- 23972660
TI  - In response to Birgir Gudjonsson, MD.

PMID- 23972661
TI  - Is there a difference in clinical efficacy of bright light therapy for different
      types of depression? A pilot study.
AB  - BACKGROUND: There is growing interest in the possible applications of Bright
      Light Therapy (BLT). BLT might be a valid alternative or add-on treatment for
      many other psychiatric disorders beyond seasonal affective disorder. This pilot
      study aims to examine whether the efficacy of Bright Light Therapy (BLT) is
      similar for different subtypes of mood disorders. METHODS: Participants were 48
      newly admitted outpatients with major depressive disorder with either melancholic
      features (n=20) or atypical features (n=28). Morning BLT was administered daily
      for 30 min at 5.000-10.000 lx on working days for up to 3 consecutive weeks.
      RESULTS: Participants' depressive symptoms improved significantly after BLT
      (p<.05, d=-.53). The effects of BLT remained stable across a 4 week follow-up.
      There were no significant differences in efficacy of BLT between groups (p>.05).
      No effect of seasonality on the improvement in depressive symptoms after BLT was
      found, (p=.781). LIMITATIONS: The study had a small sample size and lacked a
      control condition. CONCLUSIONS: This pilot study provides preliminary evidence
      that BLT could be a promising treatment for depression, regardless of the
      melancholic or atypical character of the depressive symptoms.

PMID- 23972662
TI  - Interoceptive awareness, positive affect, and decision making in major depressive
      disorder.
AB  - BACKGROUND: Little work has examined the relation between interoceptive awareness
      and symptoms of Major Depressive Disorder (MDD). Existing research suggests that
      depressed individuals exhibit impaired heartbeat perception, though the results
      of this research have been equivocal. Importantly, depressed participants in
      these studies have had comorbid anxiety disorders, making it difficult to draw
      inferences about interoceptive awareness in MDD. The current study addresses this
      issue by assessing heartbeat perception in depressed women without current
      anxiety disorders and exploring the relation between interoception and
      perturbations in both affective intensity and decision making, components of MDD
      postulated to be related to bodily awareness. METHODS: Depressed women without
      concurrent anxiety disorders (n=25) and never-disordered controls (n=36)
      performed a heartbeat perception task. Participants completed the self-report
      Affect Intensity Measure (AIM), and decision-making difficulty was assessed in
      MDD participants using the Structured Clinical Interview for DSM-IV. RESULTS:
      Depressed women exhibited poorer heartbeat perception accuracy than did control
      participants. Impaired accuracy in MDD participants was associated with reduced
      positive affectivity and difficulty in decision making. LIMITATIONS: Our sample
      was composed exclusively of females and was heterogeneous with respect to
      treatment status, thereby limiting our ability to generalize results to depressed
      males and to exclude the contribution of exogenous factors to the observed group
      differences. CONCLUSIONS: Results of this study suggest that for depressed
      individuals without anxiety comorbidities, disrupted perception of bodily
      responses reduces both the experience of positive arousal and the ability to use
      interoceptive feedback to inform decision making.

PMID- 23972663
TI  - From old alkylating agents to new minor groove binders.
AB  - Alkylating agents represent the oldest class of anticancer agents with the
      approval of mechloretamine by the FDA in 1949. Even though their clinical use is
      far beyond the use of new targeted therapies, they still occupy a major place in
      the treatment of specific malignancies, sometimes representing the unique option
      for the treatment of refractory tumors. Here, we are reviewing the major classes
      of alkylating agents, with a particular focus on the latest generations of
      compounds that specifically target the minor groove of the DNA. These naturally
      occurring derivatives have a unique mechanism of action that explains the recent
      regain of interest in developing new classes of alkylating agents that could be
      used in combination with other anticancer drugs to enhance tumor response in the
      clinic.

PMID- 23972664
TI  - Models for mature T-cell lymphomas--a critical appraisal of experimental systems
      and their contribution to current T-cell tumorigenic concepts.
AB  - Mature T-cell lymphomas/leukemias (MTCL) have been understudied lymphoid
      neoplasms that currently receive growing attention. Our historically rudimentary
      molecular understanding and dissatisfactory interventional success in this
      complex and for the most part poor-prognostic group of tumors is only slightly
      improving. A major limiting aspect in further progress in these rare neoplasms is
      the lack of suitable model systems that would substantially facilitate pathogenic
      studies and pre-clinical drug evaluations. Such representations of MTCL have thus
      far not been systematically appraised. We therefore provide an overview on
      existing models and point out their particular advantages and limitations in the
      context of the specific scientific questions. After addressing issues of species
      specific differences and classifications, we summarize data on MTCL cell lines of
      human as well as murine origin, on murine strain predispositions to MTCL, on
      available models of genetically engineered mice, and on transplant systems. From
      an in-silico meta-analysis of available primary data of gene expression profiles
      on human MTCL we cross-reference genes reported to transform T-cells in mice and
      reflect on their general vs entity-restricted relevance and on target-promoter
      influences. Overall, we identify the urgent need for new models of higher
      fidelity to human MTCL with respect to their increasingly recognized diversity
      and to predictions of drug response.

PMID- 23972665
TI  - Is reproduction of the snail Physella acuta affected by endocrine disrupting
      compounds? An in situ bioassay in three Iberian basins.
AB  - An in situ bioassay was conducted in three Iberian basins (Ebro, Llobregat and
      Jucar Rivers) to study the reproductive effects on the freshwater snail Physella
      acuta. Adult individuals were transplanted in specially designed cylindrical
      cages. Endpoints included mortality, number of eggs and clutches, number of eggs
      per clutch and embryo development after 8 days. The results were contrasted with
      laboratory controls. Significant changes in P. acuta reproduction parameters were
      detected in all of the rivers: the number of clutches or eggs per snail decreased
      in the Ebro and Llobregat basins downstream but the number of eggs per clutch
      increased. The complete development of snails was delayed at some sites
      downstream in the Jucar and the Ebro basins. The results were contrasted with
      concentrations of Endocrine Disrupting Compounds (EDCs) and their Estrogenic
      Equivalent Quotients (EEQs). Positive relationships (Pearson correlations) were
      identified between the number of eggs per clutch and the total EDC concentration,
      bisphenol A (BPA) and their EEQs, lipid regulators and diuretics. These endocrine
      disrupting chemicals may constitute a toxicological risk for the reproductive
      performance of snails in the studied basins.

PMID- 23972666
TI  - Novel preparation of carbon-TiO2 composites.
AB  - Carbon-TiO2 sulfated composites were obtained from TiOSO4 . xH2O and glycerol as
      the TiO2 and carbon sources, respectively. The precursor xerogels were prepared
      in a one-step ultrasonic-assisted sol-gel reaction, followed by thermal treatment
      at 400 degrees C under a nitrogen atmosphere to produce carbon-TiO2 sulfated
      composites. XRD, micro-Raman, SEM, and TEM studies showed that the composites
      consisted of nanocrystalline clusters of TiO2 and carbon. Ultrasonication in
      glycerol promoted the crystallinity of the xerogel precursors prior to thermal
      treatment. X-ray powder diffraction and Raman spectroscopy studies confirmed that
      glycerol also facilitated the formation of small crystallites. The band gaps of
      carbon-TiO2 composites with two different carbon loadings were found to be 3.06
      eV and 2.69 eV. By contrast, the band gap of TiO2 prepared by our method was 3.53
      eV. Calcination of the precursors led to an unusual increase in the specific
      surface and porosity of the composites compared to TiO2. The photocatalytic
      activities of the prepared composites were tested in a decomposition assay of
      Acid Orange 7. The reaction was monitored by UV-vis spectrophotometry and by LC
      ESI-(Qq)-TOF-MS-DAD. Some intermediate species were identified by LC-ESI-QTOF-MS.

PMID- 23972667
TI  - Waste biomass adsorbents for copper removal from industrial wastewater--a review.
AB  - Copper (Cu(2+)) containing wastewaters are extensively released from different
      industries and its excessive entry into food chains results in serious health
      impairments, carcinogenicity and mutagenesis in various living systems. An array
      of technologies is in use to remediate Cu(2+) from wastewaters. Adsorption is the
      most attractive option due to the availability of cost effective, sustainable and
      eco-friendly bioadsorbents. The current review is dedicated to presenting state
      of the art knowledge on various bioadsorbents and physico-chemical conditions
      used to remediate Cu(2+) from waste streams. The advantages and constraints of
      various adsorbents were also discussed. The literature revealed the maximum Cu
      adsorption capacities of various bioadsorbents in the order of algae>agricultural
      and forest>fungal>bacterial>activated carbon>yeast. However, based on the average
      Cu adsorption capacity, the arrangement can be: activated
      carbon>algal>bacterial>agriculture and forest-derived>fungal>yeast biomass. The
      data of Cu removal using these bioadsorbents were found best fit both Freundlich
      and Langmuir models. Agriculture and forest derived bioadsorbents have greater
      potential for Cu removal because of higher uptake, cheaper nature, bulk
      availability and mono to multilayer adsorption behavior. Higher costs at the
      biomass transformation stage and decreasing efficiency with desorption cycles are
      the major constraints to implement this technology.

PMID- 23972668
TI  - Towards models for the prediction of beef meat quality during cooking.
AB  - Heating of beef muscles modifies the water content, the micronutrient content and
      the colour of beef meat. Juice expelling and loss of water soluble micronutrients
      were predicted by combined transfer-kinetics models. Kinetics modeling and crust
      formation are needed to progress toward a reliable prediction of HAAs formation.
      HAAs formation in uniformly heated beef meat slices was compared with the values
      issued from the kinetic models developed in literature in liquid systems. The
      models of literature were adapted to meat slices but the parameter values were
      different from those determined in liquid systems. Results in meat slices were
      confronted to the HAAs formation at the surface of bigger meat pieces subjected
      to air roasting conditions. The transposition of the results from the meat slices
      towards the bigger meat pieces was not direct because the formation of HAAs was
      affected by the thickening of the crust and the migration of precursors. 

PMID- 23972669
TI  - Nurses and the Affordable Care Act.

PMID- 23972670
TI  - Cultural competence or code for racism?

PMID- 23972671
TI  - Circulating levels of 25-hydroxyvitamin D and prostate cancer prognosis.
AB  - OBJECTIVES: Ecological, in vitro, and in vivo studies demonstrate a link between
      vitamin D and prostate tumor growth and aggressiveness. The goal of this study
      was to investigate whether plasma concentration of vitamin D is associated with
      survivorship and disease progression in men diagnosed with prostate cancer.
      MATERIALS AND METHODS: We conducted a population-based cohort study of 1476
      prostate cancer patients to assess disease recurrence/progression and prostate
      cancer-specific mortality (PCSM) risks associated with serum levels of 25(OH)
      vitamin D [25(OH)D]. RESULTS: There were 325 recurrence/progression and 95 PCSM
      events during an average of 10.8 years of follow-up. Serum levels of 25(OH)D were
      not associated with risk of recurrence/progression or mortality. Clinically
      deficient vitamin D levels were associated with an increased risk of death from
      other causes. CONCLUSIONS: We did not find evidence that serum vitamin D levels
      measured after diagnosis affect prostate cancer prognosis. Lower levels of
      vitamin D were associated with risk of non-prostate cancer mortality.

PMID- 23972672
TI  - Association between serum levels of organochlorine pesticides and sex hormones in
      adults living in a heavily contaminated area in Brazil.
AB  - BACKGROUND: Several studies have investigated the effects of organochlorine (OC)
      pesticides on adverse reproductive outcomes. However, few previous studies
      explored their effects on sex hormones. OBJECTIVE: To examine the association
      between serum concentrations of OC pesticides and levels of sex hormones in adult
      population in a rural area in Brazil heavily contaminated with these pesticides.
      METHODS: A cross-sectional study with 304 men and 300 women was undertaken. Wet
      weight serum concentrations of 19 OC pesticides (dichloro-diphenyl
      trichloroethane [DDT] and hexachlorocyclohexane [HCH], among others) were
      determined in all participants. Testosterone levels were obtained for men and
      estradiol, progesterone, prolactin, luteinizing hormone (LH) and follicle
      stimulating hormone (FSH) for women. Associations between OC pesticides and sex
      hormones were evaluated using linear regression models. RESULTS: Prevalence of
      women with non-physiological hyperprolactinemia was 4%. After adjusting for serum
      lipids and confounders, heptachlor and o,p'-DDT concentrations in men were
      associated with lower testosterone levels, while peri- and postmenopausal women
      (N=77) showed inverse associations between LH and hexachlorobenzene (HCB), p,p'
      DDT, p,p'-DDD (dichloro-diphenyl-dichloroethane), endosulfan 1 and 2, aldrin and
      mirex, as well as between FSH and p,p'-DDD, endosulfan 1 and aldrin.
      Premenopausal women (N=210) did not show statistically significant associations
      between OC pesticides and sex hormones. CONCLUSIONS: Inverse associations between
      OC pesticide concentrations and testosterone in men and LH and FSH in peri
      /postmenopausal women, together with the high proportion of women with elevated
      prolactin, suggest that these OC compounds may have triggered anti-androgenic
      effects in men and estrogenic effects in women in this population.

PMID- 23972673
TI  - Vitamin D and diabetes: the odd couple.
AB  - The beneficial effects of vitamin D supplementation for several health-related
      issues, including the prevention of diabetes, are a topic of intense discussion.
      Data from epidemiological studies suggest a correlation between vitamin D
      deficiency and higher prevalence of both type 1 and type 2 diabetes (T1D and
      T2D). In animal models, vitamin D deficiency predisposes to diabetes whereas
      vitamin D supplementation prevents disease. Nevertheless, well-designed clinical
      intervention studies are lacking. We discuss here the evidence for a role of
      vitamin D in diabetes and propose that vitamin D deficiency should be avoided,
      especially in all at-risk people. This should be possible by implementing global
      guidelines and by focusing on daily dietary supplementation with small doses of
      vitamin D. 

PMID- 23972674
TI  - Antifoaming effect of chemical compounds in manure biogas reactors.
AB  - A precise and efficient antifoaming control strategy in bioprocesses is a
      challenging task as foaming is a very complex phenomenon. Nevertheless, foam
      control is necessary, as foam is a major operational problem in biogas reactors.
      In the present study, the effect of 14 chemical compounds on foam reduction was
      evaluated at concentration of 0.05%, 0.1% and 0.5% v/v(sample), in raw and
      digested manure. Moreover, two antifoam injection methods were compared for foam
      reduction efficiency. Natural oils (rapeseed and sunflower oil), fatty acids
      (oleic, octanoic and derivative of natural fatty acids), siloxanes
      (polydimethylsiloxane) and ester (tributylphosphate) were found to be the most
      efficient compounds to suppress foam. The efficiency of antifoamers was dependant
      on their physicochemical properties and greatly correlated to their chemical
      characteristics for dissolving foam. The antifoamers were more efficient in
      reducing foam when added directly into the liquid phase rather than added in the
      headspace of the reactor.

PMID- 23972675
TI  - Photochemical transformation of ibuprofen into harmful 4-isobutylacetophenone:
      pathways, kinetics, and significance for surface waters.
AB  - The harmful compound 4-isobutylacetophenone (IBAP) can be formed photochemically
      from the anti-inflammatory drug ibuprofen (IBP), upon direct photolysis (yield 25
      +/- 7%, MU +/- sigma), reaction with .OH (yield 2.3 +/- 0.1%) and reaction with
      triplet states of chromophoric dissolved organic matter, (3)CDOM* (yield 31 +/-
      4%). In the latter case, anthraquinone-2-sulphonate was used as CDOM proxy. The
      three processes would account for most of the photochemical transformation of IBP
      and IBAP in surface waters. IBAP formation from IBP involves the propanoic acid
      chain, which is more reactive than the aromatic ring as shown by quantum
      mechanical calculations. IBAP is expected to undergo slightly faster
      photochemical transformation than IBP in surface waters, with a modelled pseudo
      first order rate constant that is higher by 1.5-1.9 times compared to IBP. Due to
      fairly high formation yields and depending on IBP emission scenarios,
      photochemical modelling suggests that IBAP could reach concentration values up to
      ~15% of IBP in surface waters, thus being a potentially important transformation
      intermediate. This issue prompts for the need of field studies that provide
      information on IBAP environmental occurrence, which is virtually unknown at the
      present moment.

PMID- 23972676
TI  - Photochemical transformation of atrazine and formation of photointermediates
      under conditions relevant to sunlit surface waters: laboratory measures and
      modelling.
AB  - By combination of laboratory experiments and modelling, we show here that the
      main photochemical pathways leading to the transformation of atrazine (ATZ, 2
      chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) in surface waters would be
      direct photolysis, reaction with .OH and with the triplet states of chromophoric
      dissolved organic matter ((3)CDOM*). Reaction with (3)CDOM* would be favoured by
      elevated water depth and dissolved organic carbon content, while opposite
      conditions would favour direct photolysis and OH reaction. Desethylatrazine (DEA,
      4-amino-2-chloro-6-isopropylamino-1,3,5-triazine) was the main detected
      intermediate of ATZ phototransformation. Its formation yield from ATZ (ratio of
      DEA formation to ATZ transformation rate) would be 0.93 +/- 0.14 for .OH, 0.55 +/
      0.05 for (3)CDOM*, and 0.20 +/- 0.02 for direct photolysis. Direct photolysis
      and .OH reaction also yielded 4-amino-2-hydroxy-6-isopropylamino-1,3,5-triazine
      (DEAOH) and 6-amino-2-chloro-4-ethylamino-1,3,5-triazine (DIA). Reaction with
      excited triplet states also produced 2-hydroxy-4,6-diamino-1,3,5-triazine (AN)
      and 2-chloro-4,6-diamino-1,3,5-triazine (CAAT). Therefore, if biological
      processes can be neglected and if the low formation yields do not prevent
      detection, DEAOH and DIA could be used as markers of ATZ direct photolysis and
      .OH reaction, while AN and CAAT could be markers of ATZ reaction with (3)CDOM*.
      Model predictions concerning ATZ phototransformation were compared with available
      field data from the literature. When sufficiently detailed field information was
      provided, good agreement was found with the model.

PMID- 23972677
TI  - Lethal doses of oxbile, peptones and thiosulfate-citrate-bile-sucrose agar (TCBS)
      for Acanthaster planci; exploring alternative population control options.
AB  - Effective control of outbreaks of Acanthaster planci represents the most
      immediate and practical intervention to reverse sustained declines in coral cover
      on reefs in the Indo-Pacific. This study explored the minimum doses of oxbile,
      oxgall, and thiosulfate-citrate-bile-sucrose agar (TCBS) that result in reliable
      and comprehensive mortality when injected into adult A. planci. The minimum doses
      required to induce 100% mortality among starfish (n=10) were 4 g l(-1) of oxbile,
      8 g l(-1) of oxgall and 22 g l(-1) of TCBS. Moreover, there was no evidence of
      unintended side effects for other coral reef organisms (e.g., scleractinian
      corals, echinoderms and fishes) when using oxbile, oxgall, or TCBS at minimum
      doses. The effectiveness of peptones in killing crown-of-thorns starfish was also
      tested, but inconsistency in the results revealed that these proteins are
      unreliable.

PMID- 23972678
TI  - Benthic foraminiferal assemblages and trace metals reveal the environment outside
      the Pearl River Estuary.
AB  - We investigated the distribution patterns of the benthic foraminiferal
      assemblages outside the Pearl River Estuary in relation to trace metals, organic
      carbon and sedimentary particle fractions. The study area is unpolluted to
      moderately polluted by Cr, Cu, Pb and Zn and is completely polluted by Ni. The
      highest levels are found in the western coastal zone. Spatial distributions of
      the measured elements are strongly related to the behavior of the sedimentary
      clay fraction. The analyses of species abundance and community diversity as well
      as subsequent canonical correspondence analysis were used to reveal the
      relationship between foraminifera data and environmental parameters. Four
      sampling site groups established by factor analysis were distributed from the
      coastal area to the inner shelf. Their distribution patterns have a strong
      correlation with Cu, Pb and Ba. This research shows that benthic foraminifera can
      be used as bioindicators of trace metal pollutants outside the Pearl River
      Estuary. 

PMID- 23972679
TI  - Mercury deposition during the previous century in an upwelling region; Cabo Frio,
      Brazil.
AB  - To investigate the upwelling influence on Hg biogeochemical cycles and the
      sedimentological changes during the previous ~ 150 years, four sediment box-cores
      were sampled along an inshore offshore transect on the Southeastern Brazilian
      continental shelf. Mercury values were found to be relatively low, with means
      ranging between 8.08 and 30.4 ng g(-1). Mercury fluxes along the sediment cores
      are directly related to the well documented historical regional activity and
      global atmospheric deposition. The narrow relationship between mercury and
      organic carbon suggest that upwelling phenomenon and primary production may play
      an important role on Hg input and distribution along continental shelf
      depositional settings.

PMID- 23972680
TI  - Monitoring cooling water discharge using Lagrangian coherent structures: a case
      study in Daya Bay, China.
AB  - As an unwanted by-product in the power plants, cooling water (CW) discharge may
      induce harmful effects on the coastal environment. In this paper, to accurately
      predict the CW transport in the Daya Bay, China, we develop a three-dimensional
      hydrodynamic and temperature model to simulate the transport of the CW from
      nuclear power plant into coastal waters. Specifically, we use the flow velocity
      produced by the model to locate Lagrangian coherent structures (LCSs) hidden in
      ocean surface currents. Result show that the transport of the CW is quite
      strongly tied to the simulated LCSs. The LCSs constitute fluid barriers that
      accurately demarcate potential pathway for CW transport. Thus, LCSs in velocity
      fields from a coastal model is an extremely useful way to monitor and interpret
      the transport of CW. 

PMID- 23972681
TI  - [Endoscopic treatment of gastrocutaneous fistula after gastric sleeve surgery].

PMID- 23972682
TI  - [Pneumatic dilation in the treatment of achalasia].
AB  - INTRODUCTION: Pneumatic dilation and surgical myotomy are currently the
      procedures of choice to treat achalasia. The selection of one or other treatment
      depends on the experience of each center and patient preferences. BACKGROUND AND
      AIMS: To review the experience of pneumatic dilation in patients with achalasia
      in our center. MATERIAL AND METHODS: We included all patients with a clinical,
      endoscopic and manometric diagnosis compatible with achalasia who underwent
      pneumatic dilation in a 19-year period. All dilations were routinely performed
      with a Rigiflex((r)) balloon, usually at pressures of 250, 250 and 300mm Hg in
      three inflations of one minute, each separated by one minute. The success of the
      dilation was assessed on the basis of the patient's symptoms, the number of
      sessions, the need for surgery, and the presence of complications. RESULTS: A
      total of 171 patients were included, 53.2% men and 46.8% women, with a mean age
      of 51.53+/-17.78 years (16-87 years), from June 1993 to October 2012. A 35-mm
      balloon was used in 157 patients, a 30-mm balloon in 9 patients and a 40-mm
      balloon in 7 patients. A single dilation session was required in 108 patients,
      two sessions were required in 56 patients, with a mean time between the first and
      second sessions of 25.23+/-43.25 months (1-215 months), and 3 sessions were
      required in 7 patients with a mean time between the second and third sessions of
      6.86+/-5.33 months (1-15 months). Outcome after dilation was successful in 81% of
      the patients. Of the 140 responders, 121 had complete response (complete
      disappearance of symptoms without recurrence) and 19 partial response (initial
      disappearance of symptoms with subsequent reappearance). Surgery (Heller myotomy)
      was required in 15.8% of the patients. Perforation occurred in 4 of the 171
      patients as a complication of the technique; these perforations were
      satisfactorily resolved, two by conservative treatment and two by surgery. There
      was no mortality associated with the technique or its complications. CONCLUSIONS:
      In our series, pneumatic dilation had a high success rate. In most patients, a
      single session was required and the complications rate was low. These results
      show that this technique is safe and effective in these patients, avoiding a
      large number of surgical interventions.

PMID- 23972683
TI  - [Prevalence and characteristics of anemia and iron deficiency in patients
      hospitalized for gastrointestinal diseases in Spain].
AB  - OBJECTIVE: To determine the prevalence and characteristics of anemia and iron
      deficiency in patients hospitalized for gastrointestinal diseases. METHODS: An
      epidemiological, multicenter, mixed design study (retrospective review of
      randomized clinical records and prospective visits) conducted between February
      2010 and March 2011 in 22 Spanish gastroenterology departments. Severe anemia was
      defined as Hb < 10g/dL, mild/moderate as Hb >= 10g/dL, and iron deficiency as
      ferritin < 30ng/ml or transferrin saturation < 16%. RESULTS: We included 379
      patients. The mean+/-SD age was 57+/-19 years and 47% were men. The prevalence of
      anemia at admission was 60% (95% CI 55 to 65), and anemia was severe (Hb <10g/dl)
      in half the patients. The prevalence of iron deficiency was 54% of evaluable
      patients (95% CI 47 to 61). Gastrointestinal bleeding at admission was found in
      39% of the patients, of whom 83% (121/146) were anemic. At discharge, the
      proportion of anemic patients was unchanged (from 60% at admission to 58% at
      discharge) (95% CI 53 to 63) and iron deficiency was found in 41% (95% CI 32 to
      50): anemia was severe in 17% and mild/moderate in 41%. During follow-up, at 3-6
      months after admission, 44% (95% CI 39 to 50) of evaluable patients continued to
      have iron deficiency and 28% (95% CI 23 to 32) were still anemic: 5% severe and
      23% mild/moderate. The prevalence of iron deficiency was 44% (95% CI: 39-50).
      During admission, 50% of patients with anemia did not receive treatment. At
      discharge, 55% were untreated. CONCLUSION: The prevalence of anemia in patients
      hospitalized for gastroenterological diseases was very high. Anemia persisted in
      over a quarter of patients at the follow-up visit. Only half of hospitalized
      patients received treatment for anemia, even when the anemia was severe.

PMID- 23972684
TI  - Training needs of nurses and social workers in the end-of-life care for people
      with intellectual disabilities: a national survey.
AB  - BACKGROUND: Nurses and social workers caring for people with intellectual
      disabilities are increasingly confronted with clients in need of end-of-life
      care. Previous studies, however, suggest that professionals in intellectual
      disability care services lack knowledge and experience concerning end-of-life
      care. Moreover, the proportion of nurses within the staff of intellectual
      disability services has declined in recent years, while the proportion of social
      workers has increased, which may have consequences for the quality of end-of-life
      care. OBJECTIVES: To gain insight into the quality of end-of-life care, past
      vocational training, training needs and expert consultation opportunities of
      nurses and social workers working in intellectual disability care services.
      DESIGN: Survey questionnaire study conducted in the Netherlands. SETTINGS:
      Intellectual disability care services. PARTICIPANTS: The study sample was
      recruited from an existing nationally representative research panel of care
      professionals. In 2011, all 181 nurses and social workers in the research panel
      who worked in intellectual disability care services were sent our survey
      questionnaire. METHODS: Postal survey addressing education, views and needs
      regarding end-of-life care. RESULTS: The response was 71.8%. Respondents
      positively evaluated the quality of end-of-life care. However, most respondents
      felt inadequately trained in end-of-life care issues. Nurses had received more
      training in end-of-life care and had fewer training needs than social workers.
      Respondents wished for additional training, especially in supporting clients in
      dealing with the impending death and farewell process. Half of the respondents
      were unaware of the availability of external consultation facilities.
      CONCLUSIONS: This study shows that although nurses and social workers positively
      appraise the quality of end-of-life care for people with intellectual
      disabilities, the majority feel inadequately trained to provide good end-of-life
      care. As the number of people with intellectual disability in need of end-of-life
      care grows, organizations need to offer additional relevant training and must
      give information about the availability of external expert consultation for
      nurses and social workers.

PMID- 23972685
TI  - Reply to Dr. Kotze's and Dr. Yamamoto's letter.

PMID- 23972687
TI  - Child and adolescent psychiatrists are often tasked with the challenge of
      treating patients in various contexts.

PMID- 23972686
TI  - Design of prospective study of acute coronary syndrome hospitalization after
      smoking ban in public places in Hyogo prefecture: comparison with Gifu, a
      prefecture without a public smoking ban.
AB  - BACKGROUND: Hyogo is the second prefecture, after Kanagawa, to enact a smoking
      ban in public places in Japan. The effect of this smoking ban on acute coronary
      syndrome (ACS) has not been evaluated. PURPOSE: Changes in the annual number of
      ACS hospital cases in Hyogo Prefecture, before and after the enactment of the
      prefectural legislative ban on smoking in public places, are to be compared with
      those in Gifu Prefecture, where there is no smoking-ban legislation. METHODS:
      Consecutive Hyogo residents with ACS, admitted to 33 major hospitals in the
      Hanshin-Awaji-Kobe district, which covers 56% of the population, during the 12
      months before implementation of the legislation (April 2012 through March 2013)
      and during the same 24 months thereafter (April 2013 through March 2015) will be
      enrolled. Consecutive patients with ACS, who are Gifu residents, treated at the
      20 major hospitals in Gifu Prefecture will be enrolled as geographical controls.
      The primary endpoint is the change in number of ACS admissions from April 2012
      through March 2015, considering the periods before and after the smoking-ban
      legislation in Hyogo prefecture. CONCLUSION: Our study has certain strengths: (1)
      This is the first large Japanese study of ACS registry with smoking-ban
      legislation. (2) Major hospitals in the Hanshin-Awaji-Kobe district are included.
      (3) The data will cover 3 years including 1 year before legislation enactment.
      (4) The data will be compared with those of Gifu Prefecture, where smoking-ban
      legislation will not be enacted. (5) The very large database makes possible
      analysis of subgroups based on age and gender.

PMID- 23972688
TI  - Transitional aged youth: a new frontier in child and adolescent psychiatry.

PMID- 23972689
TI  - Past imperfect, future tense: psychotherapy and child psychiatry.

PMID- 23972690
TI  - Gym for the attention-deficit/hyperactivity disorder brain? Still a long run
      ahead....

PMID- 23972691
TI  - Social disadvantage and exclusion: adults with autism lag far behind in
      employment prospects.

PMID- 23972692
TI  - Protection from genetic diathesis in attention-deficit/hyperactivity disorder:
      possible complementary roles of exercise.
AB  - OBJECTIVE: The degree of functional impairment and adverse developmental outcomes
      in individuals with attention-deficit/hyperactivity disorder (ADHD) likely
      reflect interplay between genes and environment. To establish whether physical
      exercise might reduce the level of ADHD symptoms or ADHD-related impairments, we
      conducted a comprehensive review of the effect of exercise in children with ADHD.
      Findings on the impact of exercise in animals and typically developing human
      beings, and an overview of putative mechanisms involved, are also presented to
      provide the context in which to understand this review. METHOD: The electronic
      databases PubMed, OVID, and Web of Knowledge were searched for all studies
      investigating the effect of exercise in children and adolescents with ADHD, as
      well as animal models of ADHD behaviors (available in January 2013). Of 2,150
      initially identified records, 16 were included. RESULTS: Animal studies indicate
      that exercise, especially early in development, may be beneficial for ADHD
      symptom reduction. The limited research investigating the effect of exercise in
      children and adolescents with ADHD suggests that exercise may improve executive
      functioning and behavioral symptoms associated with ADHD. Although animal
      research suggests that brain-derived neurotrophic factor (BDNF) and
      catecholamines (CAs) play a role in mediating these effects, the association
      between BDNF and ADHD remains unclear in human beings. CONCLUSIONS: The potential
      protective qualities of exercise with regard to reducing symptoms and impairments
      commonly associated with ADHD may hold promise for the future. Further research
      is needed to firmly establish whether there are clinically significant effects of
      exercise on the severity of ADHD symptoms, impairments, and associated
      developmental outcomes.

PMID- 23972693
TI  - Two-year impact of personality-targeted, teacher-delivered interventions on youth
      internalizing and externalizing problems: a cluster-randomized trial.
AB  - OBJECTIVE: To assess the 2-year impact of teacher-delivered, brief, personality
      targeted interventions on internalizing and externalizing symptoms in an
      adolescent U.K. sample. METHOD: This cluster-randomized trial was run in 19
      London schools (N = 1,024 adolescents). Trained school-based professionals
      delivered two 90-minute, CBT-based group interventions targeting 1 of 4
      personality-risk profiles: anxiety sensitivity, hopelessness, impulsivity, or
      sensation seeking. Self-report depression, anxiety, and conduct disorder symptoms
      were assessed at 6-month intervals. RESULTS: Interventions were associated with
      significantly reduced depressive, anxiety, and conduct symptoms (p < .05) over 2
      years in the full sample, reduced odds of severe depressive symptoms (odds ratio
      [OR] = 0.74, CI = 0.58-0.96), and conduct problems (OR = 0.79, CI = 0.65-0.96),
      and a nonsignificant reduction in severe anxiety symptoms (OR = 0.79, CI = 0.59
      1.05). Evaluating a priori personality-specific hypotheses revealed strong
      evidence for impulsivity-specific effects on severe conduct problems, modest
      evidence of anxiety sensitivity-specific effects on severe anxiety, and no
      evidence for hopelessness-specific effects on severe depressive symptoms.
      CONCLUSIONS: Brief, personality-targeted interventions delivered by educational
      professionals can have a clinically significant impact on mental health outcomes
      in high-risk youth over 2 years, as well as personality-specific intervention
      effects in youth most at risk for a particular problem, particularly for youth
      with high levels of impulsivity. Clinical trial registration information
      Adventure: The Efficacy of Personality-Targeted Interventions for Substance
      Misuse and Other Risky Behaviors as Delivered by Educational Professionals.

PMID- 23972694
TI  - Randomized, double-blind trial of guanfacine extended release in children with
      attention-deficit/hyperactivity disorder: morning or evening administration.
AB  - OBJECTIVE: To examine the efficacy and tolerability of guanfacine extended
      release (GXR) administered in the morning or evening in children with attention
      deficit/hyperactivity disorder (ADHD). METHOD: In this multicenter, double-blind,
      placebo-controlled, dose-optimization study, children 6 to 12 years of age with
      ADHD were randomized to receive GXR (1-4 mg/d) in the morning and placebo in the
      evening (GXR am), placebo in the morning and GXR in the evening (GXR pm), or
      twice-daily placebo. The primary efficacy measure was the ADHD Rating Scale-IV
      (ADHD-RS-IV). RESULTS: A total of 333 child participants received study drug in
      the following cohorts: GXR am (n = 107), GXR pm (n = 114), or placebo (n = 112).
      Mean (standard deviation) changes from baseline to week 8 (visit 10 or last
      observation carried forward) in ADHD-RS-IV total scores were significant for both
      GXR treatment groups combined (GXR all-active: -20.0 [12.97]) and separately (GXR
      am: -19.8 [12.95]; GXR pm: -20.1 [13.04]) compared with placebo (-11.0 [12.93]; p
      < .001 for all). Most spontaneously-elicited treatment-emergent adverse events
      were mild or moderate in severity; the most common was somnolence (GXR all
      active: 44.3%; GXR am: 46.7%; GXR pm: 42.1%; placebo: 12.5%). CONCLUSIONS: GXR
      administered either in the morning or evening was associated with significant and
      clinically meaningful improvements in ADHD symptoms. The levels of response and
      tolerability observed with GXR were similar regardless of time of dosing (morning
      versus evening), indicating that once-daily GXR monotherapy is effective whether
      administered in the morning or evening. Clinical trial registration information
      Tolerability and Efficacy of AM and PM Once Daily Dosing With Extended-release
      Guanfacine Hydrochloride in Children 6-12 With Attention-Deficit/Hyperactivity
      Disorder (ADHD) (The ADHD Tempo Study.

PMID- 23972696
TI  - Childhood maltreatment and psychopathology affect brain development during
      adolescence.
AB  - OBJECTIVE: The hippocampus and amygdala have received much attention with regard
      to the deleterious effects of childhood maltreatment. However, it is not known if
      and when these effects emerge during adolescence and whether comorbid
      psychopathology is more likely to explain these effects. This study investigated
      whether childhood maltreatment was associated with hippocampal and amygdala
      development from early to midadolescence and whether the experience of
      psychopathology during this period mediated the relation. METHOD: One hundred
      seventeen (60 male) adolescents, recruited as part of a broader adolescent
      development study, participated in magnetic resonance imaging assessments during
      early and midadolescence (mean age at baseline 12.62 years, SD 0.44 years; mean
      follow-up period 3.78 years, SD 0.20 years), and completed self-report
      measurements of childhood maltreatment and diagnostic interviews assessing DSM-IV
      mental disorders. RESULTS: Childhood maltreatment was associated with larger
      baseline left hippocampal volumes and retarded growth of the left amygdala over
      time and was indirectly associated, through the experience of psychopathology,
      with retarded growth of the left hippocampus and accelerated growth of the left
      amygdala over time. Exploratory cortical analysis showed that maltreatment
      influenced thickening of the superior parietal region through the experience of
      psychopathology. CONCLUSIONS: Childhood maltreatment was associated with altered
      brain development during adolescence. The experience of Axis I psychopathology
      during adolescence may be one mechanism by which childhood maltreatment has
      continuing effects on brain development during the adolescent years. These
      findings highlight the importance of early intervention for individuals who have
      experienced childhood maltreatment.

PMID- 23972695
TI  - Postsecondary employment experiences among young adults with an autism spectrum
      disorder.
AB  - OBJECTIVE: We examined postsecondary employment experiences of young adults with
      an autism spectrum disorder (ASD) and compared these outcomes with those of young
      adults with different disabilities. METHOD: Data were from Wave 5 of the National
      Longitudinal Transition Study-2 (NLTS2), a nationally representative survey of
      young adults who had received special education services during high school. We
      examined the prevalence of ever having had, and currently having, a paid job at
      21 to 25 years of age. We analyzed rates of full-time employment, wages earned,
      number of jobs held since high school, and job types. RESULTS: Approximately one
      half (53.4%) of young adults with an ASD had ever worked for pay outside the home
      since leaving high school, the lowest rate among disability groups. Young adults
      with an ASD earned an average of $8.10 per hour, significantly lower than average
      wages for young adults in the comparison groups, and held jobs that clustered
      within fewer occupational types. Odds of ever having had a paid job were higher
      for those who were older, from higher-income households, and with better
      conversational abilities or functional skills. CONCLUSIONS: Findings of worse
      employment outcomes for young adults with an ASD suggest that this population is
      experiencing particular difficulty in successfully transitioning into employment.
      Research is needed to determine strategies for improving outcomes as these young
      adults transition into adulthood.

PMID- 23972697
TI  - Health insurance and treatment of adolescents with co-occurring major depression
      and substance use disorders.
AB  - OBJECTIVE: The goals of this study were to identify treatment rates among
      adolescents with co-occurring major depressive episode (MDE) and substance use
      disorder (SUD), and to examine the role of health insurance in the treatment of
      these disorders. METHOD: Seven years of cross-sectional data (2004-2010) were
      pooled from the National Survey on Drug Use and Health to derive a nationally
      representative sample of 2,111 adolescents who had both a past-year MDE and SUD
      and whose insurance status was known. The associations of public and private
      insurance with MDE and SUD treatment were examined using multinomial logistic
      regressions that controlled for health status and sociodemographic variables.
      RESULTS: Less than one-half (48%) of adolescents received any form of MDE
      treatment in the past year, and only 10% received any form of SUD treatment. Only
      16% of adolescents who received MDE treatment also received SUD treatment.
      Relative to no insurance, public insurance was associated with an increased
      likelihood of receiving MDE treatment alone, but not with an increased likelihood
      of receiving both MDE and SUD treatment. Involvement in the criminal justice
      system was the major factor affecting the likelihood that an adolescent would
      receive both MDE and SUD treatment, as opposed to either no treatment or
      treatment for MDE alone. CONCLUSIONS: Exceptionally low rates of SUD treatment
      were observed in this high-risk sample. Study findings highlight a missed
      opportunity to assess and to treat SUD among adolescents with co-occurring MDE
      and SUD who have received some form of MDE treatment in the past year.

PMID- 23972698
TI  - Developmental continuity of oppositional defiant disorder subdimensions at ages
      8, 10, and 13 years and their distinct psychiatric outcomes at age 16 years.
AB  - OBJECTIVE: To test the developmental continuity, interrelationships, and
      predictive associations of the oppositional defiant disorder (ODD) subdimensions
      of irritable, headstrong, and hurtful. METHOD: Data were collected from 6,328
      mother-child pairs participating in the Avon Longitudinal Study of Parents and
      Children (United Kingdom). RESULTS: Developmental continuity for each
      subdimension was strong and interrelationships indicated that headstrong was
      associated mainly with irritable, whereas irritable did not cross associate with
      other ODD subdimensions; and hurtful was associated with lower levels of
      headstrong. With regard to associations at age 16 years, irritable at age 13
      years was associated with depression, whereas headstrong at 13 was associated
      with delinquency and callous attitude; at age 13, hurtful failed to associate
      with any of the 3 age 16 outcomes. CONCLUSIONS: The results suggest that the ODD
      headstrong and irritable subdimensions are developmentally distinct, with small
      cross-over (i.e., headstrong to irritable), and are associated with unique
      outcomes. Hurtful does not appear to be associated with future maladjustment in
      children.

PMID- 23972700
TI  - Practice parameter for the assessment and treatment of children and adolescents
      with schizophrenia.
AB  - This Practice Parameter reviews the literature on the assessment and treatment of
      children and adolescents with schizophrenia. Early-onset schizophrenia is
      diagnosed using the same criteria as in adults and appears to be continuous with
      the adult form of the disorder. Clinical standards suggest that effective
      treatment includes antipsychotic medications combined with psychoeducational,
      psychotherapeutic, and educational interventions. Since this Practice Parameter
      was last published in 2001, several controlled trials of atypical antipsychotic
      agents for early-onset schizophrenia have been conducted. However, studies
      suggest that many youth with early-onset schizophrenia do not respond adequately
      to available agents and are vulnerable to adverse events, particularly metabolic
      side effects. Further research is needed to develop more effective and safer
      treatments. 

PMID- 23972701
TI  - Variations in the anatomy of the celiac trunk: A systematic review and clinical
      implications.
AB  - The normal pattern of the celiac trunk (CT) implies its bifurcation to three
      branches, the common hepatic, the splenic and the left gastric artery. According
      to the available literature the CT presents several anatomical variations. The
      purpose of our study is to investigate the different types of these variations,
      the corresponding incidences and the probable influence of genetic factors, as
      they are presented in the existing literature. Four databases were searched for
      eligible articles for the period up to January 2013 and a total of 36 studies
      were collected. The CT was trifurcated into the three basic branches in the
      89.42% (10,906/12,196) of the cases. Bifurcation of the CT occurred in the 7.40%
      of the pooled samples (903/12,196). Absence of the CT was the rarest variation
      with a percentage of 0.38% (46/12,196), hepatosplenomesenteric trunk was found in
      49 out of the 12,196 cases (0.40%) and the celiacomesenteric trunk presented an
      incidence of 0.76% (93/12,196). Other variations of the CT were detected in the
      1.64% of the pooled cases (199/12,196). The 14.9% of the cases in the cadaveric
      series (489/3278 specimens), the 10.5% in the imaging series (675/6501 specimens)
      and the 4.6% (104/2261) in the liver transplantation series presented variations.
      These differences are statistically significant (p<0.001). The Japanese and
      Korean populations presented more variations in the CT than Caucasians (p<0.05
      and p<0.001). Negro, colored and black populations presented more variations of
      the CT than Indian ones (p>0.05). Using those data, a novel classification of CT
      variations is proposed.

PMID- 23972702
TI  - S100B overexpression increases behavioral and neural plasticity in response to
      the social environment during adolescence.
AB  - Genetic variants as well as increased serum levels of the neurotrophic factor
      S100B are associated with different psychiatric disorders. However, elevated
      S100B levels are also related to a better therapeutic outcome in psychiatric
      patients. The functional role of elevated S100B in psychiatric disorders is still
      unclear. Hence, this study was designed in order to elucidate the differential
      effects of S100B overexpression in interaction with chronic social stress during
      adolescence on emotional behavior and adult neurogenesis. S100B transgenic and
      wild-type mice were housed either in socially stable or unstable environments
      during adolescence, between postnatal days 28 and 77. In adulthood, anxiety
      related behavior in the open field, dark-light, and novelty-induced suppression
      of feeding test as well as survival of proliferating hippocampal progenitor cells
      were assessed. S100B transgenic mice revealed significantly reduced anxiety
      related behavior in the open field compared to wild-types when reared in stable
      social conditions. In contrast, when transgenic mice grew up in unstable social
      conditions, their level of anxiety-related behavior was comparable to the levels
      of wild-type mice. In addition, S100B overexpressing mice from unstable housing
      conditions displayed higher numbers of surviving newborn cells in the adult
      hippocampus which developed into mature neurons. In conclusion, elevated S100B
      levels increase the susceptibility to environmental stimuli during adolescence
      resulting in more variable behavioral and neural phenotypes in adulthood. In
      humans, this increased plasticity might lead to both, enhanced risk for
      psychiatric disorders in negative environments and improved therapeutic outcome
      in positive environments. 

PMID- 23972703
TI  - Reverse Warburg effect in a patient with aggressive B-cell lymphoma: is lactic
      acidosis a paraneoplastic syndrome?

PMID- 23972704
TI  - Biology and treatment of advanced renal cell carcinoma: a global perspective.

PMID- 23972706
TI  - Refining the use of cytoreductive nephrectomy in metastatic renal cell carcinoma.
AB  - Cytoreductive nephrectomy (CN) was regarded standard of care for patients with
      metastatic renal cellcarcinoma (mRCC) in the cytokine era. After the introduction
      of therapies targeting the vascular endothelial growth factor (VEGF) and
      mammalian target of rapamycin (mTOR) pathways, improved median survival and
      primary tumor responses are observed. Prognostic models have been validated and
      the clinical significance of tumor heterogeneity and histological subtypes has
      been recognized. These changes in the understanding and treatment of mRCC require
      assessment of CN. This review discusses the original context in which the
      efficacy of CN was established and the advances in treatment that have changed
      that context. Potential refinements in the use of CN that may reduce overall
      morbidity by limiting its use to those most likely to benefit are reviewed. 

PMID- 23972705
TI  - The molecular biology of renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) includes a variety of disparate diseases, each of
      which displays interesting and novel molecular features, challenging some of the
      central tenets of cancer biology and lending unique insights into cancer
      promoting mechanisms. The prevailing literature has focused on the most common
      type, the clear cell renal cell carcinoma (ccRCC) subgroup, in which familial and
      sporadic disease demonstrate similar molecular profiles. ccRCC is dominated by
      inactivating mutations in VHL, leading to constitutive activation of the hypoxia
      inducible factors (HIFs) and resultant hypoxia response transcription signature,
      including changes that markedly affect cellular metabolic programs. Recent
      studies in ccRCC also have implicated mutations in regulators of chromatin
      remodeling and histone methylation. Although papillary and chromophobe
      histologies of RCC are highly distinct genetically, both have disruptions in
      metabolic signaling, suggesting that modulations of basic bioenergetics pathways
      may regulate kidney cell fates and phenotypes. Finally, emerging evidence of
      tumor heterogeneity and convergent evolution is reshaping our understanding of
      how these tumors evolve, underscoring which genetic events are driver mutations,
      and prompting further consideration of how to interpret molecular analyses of
      primary tumors in making assessments related to metastatic disease. The past few
      years have been a period of rapid discovery, which have expanded the
      opportunities for the renal cancer field to leverage new knowledge into
      developing diagnostic and therapeutic strategies. 

PMID- 23972707
TI  - Systemic treatment options for untreated patients with metastatic clear cell
      renal cancer.
AB  - The introduction of therapy targeting vascular endothelial growth factor (VEGF)
      and the mammalian target of rapomycin (mTOR) has significantly improved the
      outcome of patients with metastatic renal cancer. In this article a comprehensive
      overview of treatment choices for previously untreated patients with metastatic
      disease is given. Both established and emerging therapeutic options are
      discussed, as are prognostic factors predicting outcome. 

PMID- 23972708
TI  - Molecular markers to predict response to therapy.
AB  - Currently approved treatments for metastatic renal cell carcinoma (RCC) include
      vascular endothelial growth factor (VEGF)-blocking agents, mammalian target of
      rapamycin (mTOR) inhibitors, and cytokine therapy. In the near future, we are
      likely to add immune checkpoint blocking agents to this list. As we develop
      treatment platforms around each therapeutic class, determining which drug is best
      for a particular patient becomes increasingly important. At this point, we do not
      have validated predictive biomarkers for patients with RCC. Here, we discuss the
      logistical challenges surrounding biomarker development, summarize the current
      crop of biomarker candidates, and explore potential avenues for the development
      of more effective predictive tools for patients with advanced RCC. 

PMID- 23972709
TI  - Predictive markers in advanced renal cell carcinoma.
AB  - Predictive markers of response to therapy are increasingly important in advanced
      renal cell carcinoma (RCC) due to the proliferation of treatment options in
      recent years. Different types of potential predictive markers may include
      clinical, toxicity-based, serum, tissue, and radiologic biomarkers. Clinical
      factors are commonly used in overall prognostic models of RCC but have limited
      utility in predicting response to therapy. Correlation between development of
      particular toxicities and response to therapy has been noted, such as the
      correlation between hypertension and response to angiogenesis-targeted therapy.
      Serum and tissue biomarkers will be covered in detail elsewhere, but factors such
      as serum lactate dehydrogenase (LDH) and circulating cytokines show promise in
      this regard. Finally, baseline or early treatment radiology studies may have
      predictive ability for longer term efficacy, with most studies to date focusing
      on functional imaging modalities such as positron emission tomography (PET)
      scans, dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), and DCE
      ultrasound (US). The ultimate goal of developing predictive biomarkers is to
      enable rational and personalized treatment strategies for patients with advanced
      RCC. 

PMID- 23972710
TI  - Sequencing therapy in metastatic renal cell cancer.
AB  - The sequencing of targeted therapy is well established in metastatic renal
      cancer. Switching between different vascular endothelial growth factor (VEGF)
      targeted therapies or VEGF-targeted therapies and mammalian target of rapamycin
      (mTOR) inhibitors are both of proven benefit. The optimal sequence remains
      unclear. Unfortunately, there is a lack of biomarkers to drive decision making.
      In this article we review the current data and describe the treatment options for
      patients. 

PMID- 23972711
TI  - Combination therapy in metastatic renal cell cancer.
AB  - The standard strategy in metastatic renal cell carcinoma (mRCC) is to use
      sequential treatment. Different pathways are known to be involved in the
      pathogenesis of mRCC and in the development of resistance to targeted drugs.
      Combinations of targeted drugs could theoretically achieve better inhibition of a
      given pathway, inhibition of different pathways, or inhibition of a pathway
      involved in the resistance to a given drug. However, there is as yet no clear
      evidence that combination therapy is of clinical benefit and excess toxicity has
      been observed. In mRCC the majority of studies have explored combinations of
      vascular endothelial growth factor (VEGF) inhibitors and mammalian target of
      rapamycin (mTOR) inhibitors. A new generation of VEGF tyrosine kinase inhibitors
      (TKIs) seems to be more tolerable, and therefore potentially easier to combine
      with other agents. Trials with PI3K/akt/mTORC1/2 inhibitor combinations and with
      other new targeted drugs are also ongoing. 

PMID- 23972712
TI  - Adjuvant therapy in renal cell carcinoma-past, present, and future.
AB  - To date, no effective adjuvant treatment for renal cell carcinoma (RCC) has been
      described, but research in this area is important since the 5-year relapse rate
      for intermediate- and high-risk early-stage RCC is 30%-40%. Metastatic RCC can be
      treated successfully with immune therapy and targeted therapy. Adjuvant trials
      with immune therapy have been conducted, but they reported no benefit in disease
      free survival, and clinical trials with targeted agents have not yet reported
      results. Further advances in our understanding of the molecular pathogenesis of
      RCC will identify additional potential targets for adjuvant treatment trials.
      Future challenges will consequently include target identification, as well as
      trial design to answer multiple trial questions concurrently, comprehensively,
      and economically. We review the past efforts, summarize the current adjuvant
      clinical trial landscape, and consider the challenges in adjuvant trials for RCC.
      Additionally, we identify potential future adjuvant trial treatments and propose
      an alternative design for future adjuvant clinical trials. 

PMID- 23972713
TI  - Immune therapy for kidney cancer: a second dawn?
AB  - Agents targeting the immune system have been a historical standard of care in
      metastatic renal cell carcinoma (RCC), but have largely been supplanted by newer
      targeted therapy. Recent insights into the regulation of an anti-tumor immune
      response has led to the development of agents that can activate immune responses
      primarily within the tumor, enabling the possibility of achieving durable tumor
      response in the absence of significant systemic toxicity. In addition, a better
      understanding of tumor immunology has raised the potential of developing
      predictive biomarkers of response to immunotherapy. Novel approaches including
      inhibition of immune checkpoints has entered clinical testing in RCC. 

PMID- 23972714
TI  - Selected toxicities of targeted therapies: presentation and management.
AB  - The introduction of targeted therapy has changed the landscape of metastatic
      renal cell carcinoma (mRCC) but has also brought challenges. One such challenge
      of treating this chronic disease is long-term therapy, which produces ongoing
      toxicity. Knowledge of the spectrum of toxicity from targeted therapy and
      appropriate and timely intervention is required to maintain adequate dosing
      required for optimal outcome. This article addresses some of the major toxicities
      of newer agents in RCC and discusses management strategies. 

PMID- 23972716
TI  - Access to targeted therapies in renal cell cancer.
AB  - There is limited access to targeted therapies for renal cancer in many parts of
      the western world. This is driven by reimbursement rather than regulatory issues.
      Indeed, only a small fraction of the global population benefits from unlimited
      reimbursement of targeted therapies. Dedicated bodies, such as the UK National
      Institute for Clinical Excellence, assess agents on their cost-effectiveness as
      well as their efficacy. The results have been disappointing for patients, with
      the majority of agents being rejected for reimbursement. Despite this trend,
      there is a general appetite to address cost and value in many part of the world.
      This article gives a current overview of this rapidly changing field. 

PMID- 23972717
TI  - TUNEL analysis of DNA fragmentation in mouse unfertilized oocytes: the effect of
      microorganisms within human follicular fluid collected during IVF cycles.
AB  - Recently we reported the presence of bacteria within follicular fluid. Previous
      studies have reported that DNA fragmentation in human spermatozoa after in vivo
      or in vitro incubation with bacteria results in early embryo demise and a reduced
      rate of ongoing pregnancy, but the effect of bacteria on oocytes is unknown. This
      study examined the DNA within mouse oocytes after 12 hours' incubation within
      human follicular fluids (n=5), which were collected from women undergoing in
      vitro fertilization (IVF) treatment. Each follicular fluid sample was cultured to
      detect the presence of bacteria. Terminal deoxynucleotidyl transferase mediated
      dUTP nick-end labeling (TUNEL) was used to label DNA fragmentation in ovulated,
      non-fertilized mouse oocytes following in vitro incubation in human follicular
      fluid. The bacteria Streptococcus anginosus and Peptoniphilus spp., Lactobacillus
      gasseri (low-dose), L. gasseri (high-dose), Enterococcus faecalis, or
      Propionibacterium acnes were detected within the follicular fluids. The most
      severe DNA fragmentation was observed in oocytes incubated in the follicular
      fluids containing P. acnes or L. gasseri (high-dose). No DNA fragmentation was
      observed in the mouse oocytes incubated in the follicular fluid containing low
      dose L. gasseri or E. faecalis. Low human oocyte fertilization rates (<29%) were
      associated with extensive fragmentation in mouse oocytes (80-100%). Bacteria
      colonizing human follicular fluid in vivo may cause DNA fragmentation in mouse
      oocytes following 12h of in vitro incubation. Follicular fluid bacteria may
      result in poor quality oocytes and/or embryos, leading to poor IVF outcomes. 

PMID- 23972715
TI  - Non-clear cell renal cancer: disease-based management and opportunities for
      targeted therapeutic approaches.
AB  - A better understanding of the biology of renal cell carcinoma (RCC) has
      significantly changed the treatment paradigm of the disease. Several novel
      vascular endothelial growth factor (VEGF) and mammalian target of rapamycin
      (mTOR) inhibitors have been approved recently by the US Food and Drug
      Administration. Unfortunately, the vast majority of clinical trials conducted
      today have been aimed to include patients with clear cell RCC, which remains the
      most common histologic subtype of the disease. Non-clear cell RCC represents
      approximately 20%-25% of all RCC patients. Non-clear cell RCC is made up of
      multiple histologic subtypes, each with a different molecular printing profile.
      Although VEGF and TORC inhibitors are commonly used in the management of this
      cohort of patients, non-clear cell histologies do not appear to be related to the
      von Hippel-Lindau gene (VHL). As such, the clinical efficacy of the existing
      agents is quite limited. There is a need to develop more rational therapeutic
      approaches that specifically target the biology of each of the different subtypes
      of non-clear cell RCC. In this review, we discuss molecular and clinical
      characteristics of each of the non-clear cell RCC subtypes and describe ongoing
      efforts to develop novel agents for this subset of patients. 

PMID- 23972718
TI  - Fourteen years of debate and workshops on the immunology of preeclampsia. Where
      are we now after the 2012 workshop?
AB  - This paper depicts an overview of debates that have taken place during the 14
      years of the International Workshops on Reproductive Immunology/Immunological
      Tolerance and Immunology of Preeclampsia. This 8th event in 2012 (Reunion island,
      overseas department of France in the Indian Ocean) witnessed a consensus among
      immunologists on the key role of regulatory T-cells in the orchestration of
      trophoblastic invasion at the maternal-fetal interface, while they represent some
      10% of the immunological cellular repertoire at the site of implantation (NK
      cells representing 70%). On the vascular side, the upregulation of carbon
      monoxide CO, metabolite of heme oxygenase-1 (HO-1; by inhibiting soluble Flt-1,
      SFlt-1, and soluble endoglin, SEng, release), explains the very promising
      protective and potentially therapeutic effect of pravastatin in preeclampsia and
      the paradoxical strong protective effect of cigarette smoking on preeclampsia.
      Finally, there was, through a study performed on Mauritius island a great
      interest in the inositol phosphoglycans P-type (IPG-P) as a reliable, cheap, and
      predictive urinary test in preeclamptic women (a few weeks before the clinical
      onset of the disease). Besides the interest of a specific test, IPG-P may also
      partially explain the global endothelial cell disease encountered in
      preeclampsia. Furthermore, the Appendix of this paper lists the programs of all
      the workshops that have taken place since 1998. 

PMID- 23972719
TI  - Heritability and linkage analysis of personality in bipolar disorder.
AB  - BACKGROUND: The many attempts that have been made to identify genes for bipolar
      disorder (BD) have met with limited success, which may reflect an inadequacy of
      diagnosis as an informative and biologically relevant phenotype for genetic
      studies. Here we have explored aspects of personality as quantitative phenotypes
      for bipolar disorder through the use of the Temperament and Character Inventory
      (TCI), which assesses personality in seven dimensions. Four temperament
      dimensions are assessed: novelty seeking (NS), harm avoidance (HA), reward
      dependence (RD), and persistence (PS). Three character dimensions are also
      included: self-directedness (SD), cooperativeness (CO), and self-transcendence
      (ST). METHODS: We compared personality scores between diagnostic groups and
      assessed heritability in a sample of 101 families collected for genetic studies
      of BD. A genome-wide SNP linkage analysis was then performed in the subset of 51
      families for which genetic data was available. RESULTS: Significant group
      differences were observed between BD subjects, their first-degree relatives, and
      independent controls for all but RD and PS, and all but HA and RD were found to
      be significantly heritable in this sample. Linkage analysis of the heritable
      dimensions produced several suggestive linkage peaks for NS (chromosomes 7q21 and
      10p15), PS (chromosomes 6q16, 12p13, and 19p13), and SD (chromosomes 4q35, 8q24,
      and 18q12). LIMITATIONS: The relatively small size of our linkage sample likely
      limited our ability to reach genome-wide significance in this study. CONCLUSIONS:
      While not genome-wide significant, these results suggest that aspects of
      personality may prove useful in the identification of genes underlying BD
      susceptibility.

PMID- 23972720
TI  - Elastic aortic properties in patients with X syndrome.
AB  - INTRODUCTION: Elastic properties of the aorta represent an important determinant
      of left ventricular function and coronary blood flow but there are few data about
      aortic stiffness in patients with X syndrome. AIM: To investigate the elastic
      aortic proprieties (aortic stiffness and distensibility) and arterial wall motion
      velocities as measured by tissue Doppler imaging (TDI) in patients with cardiac X
      syndrome. MATERIALS AND METHODS: Fifteen patients with X syndrome (typical chest
      pain and angiographically normal coronary arteries associated with a positive
      exercise test) were enrolled in the study. The control group consisted of 15
      healthy patients. The aortic elastic indexes, namely distensibility (cm(2) dyne(
      1)) and stiffness index (beta index) were calculated from M-mode
      echocardiographically-derived thoracic aortic diameters using accepted formulae,
      and TDI parameters were measured on the wall of the ascending aorta 3 cm above
      the aortic valve. Anterior wall aortic expansion velocity (S), early (E) and late
      (A) diastolic retraction velocity and peak systolic strain were determined.
      RESULTS: Aortic elastic proprieties were more impaired in the syndrome X group
      than in the control group. Aortic distensibility was significantly lower in the
      syndrome X group (3.2 +/- 1.3 vs. 7.95 +/- 4 cm(2) dyne(-1), p<0.001), while
      stiffness index was higher (7.3 +/- 2.1 vs. 4.1 +/- 1.6, p<0.001) than in the
      control group. Peak systolic (S) and diastolic waves (E and A waves) of the
      aortic wall TDI were similar in patients and controls (S wave: 5.7 +/- 1.6 cm/s
      vs. 5.8 +/- 1.6 cm/s, E wave: -4.8 +/- 2.0 vs. -4.1 +/- 2.0 cm/s; A wave: -4.32
      +/- 2.1 vs. -4.76 +/- 1.8 cm/s) while tissue strain of the aortic wall was lower
      in patients with X syndrome than controls (-12.80 +/- 7% vs. -22.3 +/- 5.9%,
      p<0.00001). CONCLUSION: Deterioration in aortic elasticity properties in patients
      with cardiac syndrome X suggests that this disease may be a more generalised
      disturbance of the vasculature.

PMID- 23972721
TI  - Factors that determine academic versus private practice career interest in
      radiation oncology residents in the United States: results of a nationwide
      survey.
AB  - PURPOSE: To determine what factors US radiation oncology residents consider when
      choosing academic or nonacademic careers. METHODS AND MATERIALS: A 20-question
      online survey was developed and sent to all US radiation oncology residents to
      assess factors that influence their career interest. Residents were asked to rate
      their interest in academics (A) versus private practice (PP) on a 0 (strong
      interest in A) to 100 (strong interest in PP) scale. Responses were classified as
      A (0-30), undecided (40-60), and PP (70-100). Residents were also asked to rank
      10 factors that most strongly influenced their career interest. RESULTS: Three
      hundred thirty-one responses were collected, of which 264 were complete and form
      the basis for this analysis. Factors that correlated with interest in A included
      having a PhD (P=.018), postgraduate year level (P=.0006), research elective time
      (P=.0003), obtaining grant funding during residency (P=.012), and number of
      publications before residency (P=.0001), but not number of abstracts accepted in
      the past year (P=.65) or publications during residency (P=.67). The 3 most
      influential factors for residents interested in A were: (1) baseline interest
      before residency; (2) academic role models; and (3) research opportunities during
      residency. The 3 most influential factors for residents interested in PP were:
      (1) baseline interest before residency; (2) academic role models; and (3)
      academic pressure and obligations. CONCLUSIONS: Interest in A correlated with
      postgraduate year level, degree, and research time during residency. Publications
      before but not during residency correlated with academic interest, and baseline
      interest was the most influential factor. These data can be used by residency
      program directors to better understand what influences residents' career
      interest.

PMID- 23972722
TI  - Use of EORTC target definition guidelines for dose-intensified salvage radiation
      therapy for recurrent prostate cancer: results of the quality assurance program
      of the randomized trial SAKK 09/10.
AB  - PURPOSE: Different international target volume delineation guidelines exist and
      different treatment techniques are available for salvage radiation therapy (RT)
      for recurrent prostate cancer, but less is known regarding their respective
      applicability in clinical practice. METHODS AND MATERIALS: A randomized phase III
      trial testing 64 Gy vs 70 Gy salvage RT was accompanied by an intense quality
      assurance program including a site-specific and study-specific questionnaire and
      a dummy run (DR). Target volume delineation was performed according to the
      European Organisation for the Research and Treatment of Cancer guidelines, and a
      DR-based treatment plan was established for 70 Gy. Major and minor protocol
      deviations were noted, interobserver agreement of delineated target contours was
      assessed, and dose-volume histogram (DVH) parameters of different treatment
      techniques were compared. RESULTS: Thirty European centers participated, 43% of
      which were using 3-dimensional conformal RT (3D-CRT), with the remaining centers
      using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT).
      The first submitted version of the DR contained major deviations in 21 of 30
      (70%) centers, mostly caused by inappropriately defined or lack of prostate bed
      (PB). All but 5 centers completed the DR successfully with their second submitted
      version. The interobserver agreement of the PB was moderate and was improved by
      the DR review, as indicated by an increased kappa value (0.59 vs 0.55), mean
      sensitivity (0.64 vs 0.58), volume of total agreement (3.9 vs 3.3 cm(3)), and
      decrease in the union volume (79.3 vs 84.2 cm(3)). Rectal and bladder wall DVH
      parameters of IMRT and VMAT vs 3D-CRT plans were not significantly different.
      CONCLUSIONS: The interobserver agreement of PB delineation was moderate but was
      improved by the DR. Major deviations could be identified for the majority of
      centers. The DR has improved the acquaintance of the participating centers with
      the trial protocol.

PMID- 23972723
TI  - Induction and persistence of large gammaH2AX foci by high linear energy transfer
      radiation in DNA-dependent protein kinase-deficient cells.
AB  - PURPOSE: To evaluate the cell response to DNA double-strand breaks induced by low
      and high linear energy transfer (LET) radiations when the catalytic subunit of
      DNA-dependent protein kinase (DNA-PKcs), an essential protein of the
      nonhomologous end-joining repair pathway, lacks kinase activity. METHODS AND
      MATERIALS: CHO10B2, a Chinese hamster ovary cell line, and its derived
      radiosensitive mutant cell line, irs-20, lacking DNA-PKcs activity, were
      evaluated after 0 to 3 Gy of gamma-rays, plateau and Bragg peak protons, and
      lithium beams by clonogenic assay, and as a measurement of double-strand breaks,
      phosphorylated H2AX (gammaH2AX) foci number and size were quantified by
      immunocytofluorescence. RESULTS: Irs-20 exhibited greater radiosensitivity and a
      higher amount of gammaH2AX foci than CHO10B2 at 6 hours after irradiation for all
      types of radiations. Remarkably, CHO10B2 and irs-20 maintained their difference
      in radiosensitivity after high-LET radiation. Six hours after low-LET radiations,
      irs-20 did not reach basal levels of gammaH2AX at high doses, whereas CHO10B2
      recovered basal levels for all doses. After high-LET radiation, only CHO10B2
      exhibited a reduction in gammaH2AX foci, but it never reached basal levels.
      Persistent foci in irs-20 confirmed a repair deficiency. Interestingly, after 30
      minutes of high-LET radiation both cell lines exhibited large foci (size>0.9
      MUm2) related to the damage nature, whereas at 6 hours irs-20 showed a higher
      amount of large foci than CHO10B2, with a 7-fold increase at 3 Gy, that could
      also be associated to radiosensitivity. CONCLUSIONS: We demonstrated, for the
      first time, an association between deficient DNA-PKcs activity and not only high
      levels of H2AX phosphorylation but also persistence and size increase of
      gammaH2AX foci after high-LET irradiation.

PMID- 23972724
TI  - The role of depression and impulsivity in the psychopathology of bulimia nervosa.
AB  - INTRODUCTION: The study aimed to analyze the role of depression and impulsivity
      in the psychopathology of bulimia nervosa (BN). MATERIALS AND METHODS: Seventy
      female patients with DSM-IV BN, purging subtype, were assessed for eating-related
      symptoms, body dissatisfaction, affective symptoms, impulsivity, and personality
      traits. Factor analysis and structural equation modeling methods were used for
      statistical analysis. RESULTS: BN appeared as a condition which incorporated 5
      general dimensions: a) binge eating and compensatory behaviours; b) restrictive
      eating; c) body dissatisfaction; d) dissocial personality traits; and e) a
      cluster of features which was called "emotional instability" The 5 obtained
      dimensions can be grouped into 2 basic factors: body dissatisfaction/eating
      behaviour and personality traits/psychopathology. The first one contains the
      clinical items used for the definition of BN as a clinical condition in the DSM-V
      and the International Classification of Diseases 10, and reflects the morphology
      and the severity of the eating-related symptoms. The second dimension includes a
      cluster of symptoms (depressive symptoms, impulsivity, and borderline, self
      defeating and dissocial personality traits) which could be regarded as the
      "psychopathological core" of BN and may be able to condition the course and the
      prognosis of BN.

PMID- 23972726
TI  - Age-related brain trajectories in schizophrenia: a systematic review of
      structural MRI studies.
AB  - Using the Pubmed database, we performed a detailed literature search for
      structural magnetic resonance imaging studies on patients with schizophrenia,
      investigating the relationship between macroscopic and microscopic structural
      parameters and age, to delineate an age-related trajectory. Twenty-six studies
      were considered for the review, from January 2000 to June 2012. Research results
      are heterogeneous because of the multifactorial features of schizophrenia and the
      multiplicity of the methodological approaches adopted. Some areas, within the
      amygdala-hippocampus complex, which are affected early in life by schizophrenia,
      age in a physiological way. Other regions, such as the superior temporal gyrus,
      appear already impaired at the onset of symptoms, undergo a worsening in the
      acute phase but later stabilize, progressing physiologically over years. Finally,
      there are regions, such as the uncinate fasciculus, which are not altered early
      in life, but are affected around the onset of schizophrenia, with their
      impairment continuously worsening over time. Further extensive longitudinal
      studies are needed to understand the timing and the possible degenerative
      characteristics of structural impairment associated with schizophrenia. 

PMID- 23972725
TI  - Plasma cytokine levels and human papillomavirus infection at the cervix in rural
      Nigerian women.
AB  - INTRODUCTION: We conducted a study to test the hypothesis that systemic
      dysregulation of Th1/Th2 cytokine levels was associated with detection of
      carcinogenic or overall human papillomavirus (HPV) at the cervix among 964 women
      residing in a rural village in Nigeria. METHODS: Levels in plasma were measured
      for 19 cytokines, including Th1-like cytokines IL-2, IL-12 (p40), TNF-a, IFN-g;
      Th2-like cytokines IL-4, IL-5, IL-6, IL-10, IL-13; innate/inflammation cytokines
      IL-1a, IL-1b, IL-8, eotaxin, MCP-1, MIP-1a, and IL-7; and cell development
      cytokines G-CSF, VEGF, and IL-17. Analysis was restricted to 5 cytokines, TNF
      alpha (Th1), IL-8 (Th2), eotaxin and MCP-1 (innate/inflammation), and G-CSF (cell
      development), whose levels were detected in 80% or more of the samples measured
      as well as had a coefficient of variation of <30%. RESULTS: Strong correlations
      were noted between levels of eotaxin and TNF-alpha (r=0.75), IL-8 and MCP-1
      (r=0.60), eotaxin and G-CSF (r=0.44), and G-CSF and IFN-gamma (r=0.43). Detection
      of carcinogenic or non-carcinogenic HPV DNA was unrelated to cytokine levels,
      except for levels of eotaxin and TNF-alpha, which were inversely correlated,
      albeit weakly, with detection of any carcinogenic HPV (P=0.048 and P=0.067,
      respectively). In analyses stratified by age group, levels of eotaxin were
      inversely correlated with detection of any HPV DNA (P=0.026) and carcinogenic HPV
      (P=0.042) in older, but not younger, women. CONCLUSIONS: Our results do not
      support the hypothesis of association between systemic cytokine dysregulation and
      detection of HPV at the cervix in Nigerian women, but subgroup analyses raise
      questions about inverse associations between eotaxin and TNF-alpha in older
      women.

PMID- 23972727
TI  - Antiinflammatory properties of a peptide derived from interleukin-4.
AB  - Interleukin-4 (IL-4) is a potent antiinflammatory cytokine. However its use in
      the clinic is hampered by side effects. We here describe the identification of a
      novel synthetic peptide, termed Ph8, derived from alpha-helix C of IL-4, which
      interacts with IL-4 receptor alpha (IL-4Ralpha). Employing various cultured
      genetically engineered cell lines and primary lymphocytes, surface plasmon
      resonance, qPCR, ELISA and immunoblotting techniques we found that Ph8 bound IL
      4Ralpha and mimicked the anti-inflammatory effects of IL-4 by inhibiting TNF
      alpha production by macrophages in vitro. It induced phosphorylation of STAT6
      65kD but inhibited phosphorylation of STAT6 110 kD induced by IL-4 in a B-cell
      line that expressed the type I receptor. It also inhibited the IL-4-stimulated
      expression of a STAT6-inducible reporter gene in cells that expressed the type II
      receptor. Ph8 inhibited the proliferation of Th1/2 cells and downregulated the
      production of IFN-gamma in stimulated Th1 cells. Moreover, Ph8 did not induce any
      shift in Th1/Th2 profile. This is a favorable effect and it is indicating that
      Ph8 could block general T cell activation and inflammatory responses without
      further inducing the side effects generally associated with IL-4 signaling. These
      data collectively show that Ph8 is only a partial agonist of IL-4 mimicking its
      desirable properties. In agreement, Ph8 treatment of rats with collagen-induced
      arthritis, a Th1- and antibody- mediated disease of joint, delayed the
      manifestation of chronic inflammation and reduced acute inflammation in
      carrageenan-induced edema. Our findings indicate that Ph8 is a promising
      potential drug candidate for the treatment of inflammatory diseases.

PMID- 23972728
TI  - The impact of thin idealized media images on body satisfaction: does body
      appreciation protect women from negative effects?
AB  - This article examines whether positive body image can protect women from negative
      media exposure effects. University women (N=112) were randomly allocated to view
      advertisements featuring ultra-thin models or control images. Women who reported
      high levels of body appreciation did not report negative media exposure effects.
      Furthermore, the protective role of body appreciation was also evident among
      women known to be vulnerable to media exposure. Women high on thin-ideal
      internalization and low on body appreciation reported appearance-discrepancies
      that were more salient and larger when they viewed models compared to the control
      group. However, women high on thin-ideal internalization and also high on body
      appreciation rated appearance-discrepancies as less important and no difference
      in size than the control group. The results support the notion that positive body
      image protects women from negative environmental appearance messages and suggests
      that promoting positive body image may be an effective intervention strategy. 

PMID- 23972729
TI  - Weight discrepancy and body appreciation among women in Poland and Britain.
AB  - Previous studies have suggested that the process of transmigration has
      detrimental effects on the body image of migrants relative to women in the
      country of origin. In the present work, we examined the body image of Polish
      migrants in Britain (n=153), Polish women in Poland (n=153), and a comparison
      group of British White women (n=110). Participants completed a measure of actual
      ideal weight discrepancy and the Body Appreciation Scale (BAS). Contrary to
      hypotheses, our results showed that Polish women in Poland had significantly
      higher weight discrepancy than their counterparts in Britain. Further analyses
      showed that the BAS reduced to two dimensions among Polish participants, with
      Polish participants in Poland having significantly lower body appreciation than
      Polish migrants. We suggest that the sociocultural changes that have taken place
      in Eastern Europe may place women in that region at relatively high risk for
      developing negative body image. 

PMID- 23972730
TI  - DDT residue contamination in sediments from Lake Sibaya in northern KwaZulu
      Natal, South Africa: implications for conservation in a World Heritage Site.
AB  - Maputaland in northern KwaZulu-Natal is a biodiversity hotspot and host to a
      number of ecologically important systems, including Lake Sibaya, southern
      Africa's largest natural freshwater lake. The region is malaria endemic and this
      study reports the presence of DDT and its metabolites in the sediments of Lake
      Sibaya that have resulted from the widespread and continued use of DDT in the
      region. DDT residues (p,p'-DDT, p,p'-DDD, and p,p'-DDE) were detected at all 11
      sites sampled, with total concentrations ranging from 0.8 to 123 ng g(-1). Total
      DDT concentrations at Lake Sibaya represent some of the highest levels reported
      in South Africa, with most samples exceeding sediment quality guideline values.
      The findings from this study raise concerns and indicate that urgent further work
      is needed to investigate the potential for bioaccumulation, which could adversely
      affect breeding fish, bird, and crocodile populations in the region. While this
      study represents the first report on DDT contamination in Lake Sibaya, results
      have important implications for a number of other aquatic ecosystems within the
      Maputaland ecoregion, as well as the many local people who depend on them.

PMID- 23972731
TI  - Development and characterization of a new gill cell line from air breathing fish
      Channa striatus (Bloch 1793) and its application in toxicology: direct comparison
      to the acute fish toxicity.
AB  - A new cell line, Channa striatus gill (CSG), derived from the gill tissue of
      murrel, was established and characterized. The CSG cell line was maintained in
      Leibovitz's L-15 supplemented with 10% fetal bovine serum and has been
      subcultured more than 92 times. This cell line was able to grow in a range of
      temperatures from 22 to 32 degrees C with optimal growth at 28 degrees C. The
      plating efficiency was very high (52.21%) and doubling time was approximately
      37h. The gill cell line was cryopreserved at different passage levels and revived
      successfully with 85% survival. Polymerase chain reaction amplification of
      mitochondrial 16S rRNA using primer specific to C. striatus confirmed the origin
      of this cell line from murrel. The cell line was further characterized by
      immunocytochemical analysis, chromosome number, transfection and mycoplasma
      detection. The cytotoxicity of endosulfan was assessed in CSG cell line using
      apoptosis assay, comet assay, mitochondrial alteration and five other endpoints
      such as Rhodamine 123 uptake, 3-(4, 5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide, neutral red assay, Alamar Blue assay and Methylene
      Blue protein assay. Acute toxicity study on fish was conducted by exposing murrel
      for 96h to endosulfan under static conditions. Statistical analysis revealed good
      correlation with r(2)=0.972-0.997 among the five endpoints. Linear correlations
      between the in vivo lethal concentration 50 (LC50) and each in vitro effective
      concentration 50 (EC50) were highly significant. The present study highlights the
      development of a new gill cell line from an air breathing fish that could be used
      as an alternative in vitro tools for studying pesticide toxicity in fish. 

PMID- 23972732
TI  - Prenatal exposure to nanoparticulate titanium dioxide enhances depressive-like
      behaviors in adult rats.
AB  - Titanium dioxide nanoparticles (TiO2 NPs) have the potential to produce reactive
      oxygen species and can be transferred from the mother to the fetal brain. The
      central nervous system exhibits remarkable plasticity in early life and can be
      altered significantly by environmental stressors encountered during fetal period.
      Additionally, prenatal stressors are involved with emotional problems in
      adulthood. The purpose of the current study is to evaluate whether prenatal
      exposure to TiO2 NPs could induce oxidative damage in the offspring brain and
      eventually affect the emotional behaviors in adulthood. The results showed that
      prenatal exposure to TiO2 NPs impaired the antioxidant status, caused a
      significant oxidative damage to nucleic acids and lipids in the brain of newborn
      pups, and enhanced the depressive-like behaviors during adulthood in the force
      swimming test and the sucrose preference test. These results suggest that the
      stress during fetal life induced by prenatal exposure to TiO2 NPs could be
      implicated in depressive-like behaviors in adulthood. 

PMID- 23972733
TI  - Functional gene expression of oil-degrading bacteria resistant to hexadecane
      toxicity.
AB  - Contamination with oil poses a threat to the environment and to human health
      worldwide. Biological methodologies have proved to be economical, versatile and
      efficient for the remediation of pollutants. In this paper, a highly efficient
      oil-degrading bacterial strain USTB-2 was isolated from an oil production well of
      Dagang oil field in Tianjin, China. The 16S rRNA sequence of USTB-2 showed 100%
      similarity with that of Bacillus subtilis BSn5. Hexadecane is one of the most
      important components in petroleum. The half inhibitory ratio (IC50) of hexadecane
      inhibited organisms, determined by microcalorimetry, was lower in USTB-2 than in
      B. BSn5. The results indicate that the strain USTB-2 degrades hexadecane to make
      it less toxic compared with the normal strain. RT-PCR was used to evaluate the
      expression of oil-degrading enzymes, specifically 4-hydroxyphenylacetate 3
      monooxygenase genes (HPMO). A sharp increase in the expression of HPMO genes was
      observed for USTB-2, while the expression of HPMO genes in reference strain B.
      BSn5 remained relatively stable. These methods can be used to study the metabolic
      potential of microorganisms for in situ oil decontamination.

PMID- 23972734
TI  - Editorial for "Methods for analysis of nitric oxide signalling by S
      nitrosylation".

PMID- 23972735
TI  - [Morphological analysis of the hippocampal region associated with an innate
      behaviour task in the transgenic mouse model (3xTg-AD) for Alzheimer disease].
AB  - INTRODUCTION: Different animal models for Alzheimer disease (AD) have been
      designed to support the hypothesis that the neurodegeneration (loss of neurons
      and synapses with reactive gliosis) associated with Abeta and tau deposition in
      these models is similar to that in the human brain. These alterations produce
      functional changes beginning with decreased ability to carry out daily and social
      life activities, memory loss, and neuropsychiatric disorders in general. Neuronal
      alteration plays an important role in early stages of the disease, especially in
      the CA1 area of hippocampus in both human and animal models. METHODS: Two groups
      (WT and 3xTg-AD) of 11-month-old female mice were used in a behavioural analysis
      (nest building) and a morphometric analysis of the CA1 region of the dorsal
      hippocampus. RESULTS: The 3xTg-AD mice showed a 50% reduction in nest quality
      associated with a significant increase in damaged neurons in the CA1 hippocampal
      area (26%+/-6%, P<.05) compared to the WT group. CONCLUSIONS: The decreased
      ability to carry out activities of daily living (humans) or nest building (3xTg
      AD mice) is related to the neuronal alterations observed in AD. These alterations
      are controlled by the hippocampus. Post-mortem analyses of the human hippocampus,
      and the CA1 region in 3xTg-AD mice, show that these areas are associated with
      alterations in the deposition of Abeta and tau proteins, which start accumulating
      in the early stages of AD.

PMID- 23972736
TI  - Complications of thoracic radiotherapy.
AB  - The issue of toxicity is a primary concern for chest irradiation, because it is a
      dose-limiting toxicity and because in some circumstances it can alleviate the
      survival benefit of radiation therapy. Potential acute and delayed side effects
      can compromise the patients' prognosis and generate significant morbidity. Here
      we review on chest complications of radiation therapy, with focus on cardiac and
      pulmonary radio-induced side effects. Most radiographic changes associated with
      thoracic irradiation are asymptomatic. However, chest irradiation generated by
      treatment of breast cancer, bronchopulmonary malignancies, or mediastinal
      lymphoma has been associated with a risk of acute radiation pneumonitis and late
      lung fibrosis. An increasing number of clinical studies suggest that some
      dosimetric factors (e.g. V20, V30, mean lung dose) should be considered for
      limiting the risk of lung toxicity. Improvements in radiation techniques as well
      as changes in indications, volumes and prescribed doses of radiation therapy
      should help to better spare lungs from irradiation and thus decreasing the risk
      of subsequent toxicity. Numerous other contributing factors should also be
      considered, such as chemotherapeutic agents, smoking, tumor topography, or
      intrinsic sensitivity. Cardiac toxicity is another clinically relevant issue in
      patients receiving radiation therapy for breast cancer or for lymphoma. This life
      threatening toxicity should be analyzed in the light of dosimetric factors
      (including low doses) but also associated systemic agents which almost carry a
      potential for additive toxicity toward myocardium or coronaries. A long-term
      follow-up of patients as well as an increasing knowledge of the underlying
      biological pathways involved in cardiac toxicity should help designing effective
      preventing strategies. 

PMID- 23972737
TI  - [ESH/ESC and French guidelines for the management of hypertension: Similarities
      and discrepancies].

PMID- 23972738
TI  - Methylene blue is associated with poor outcomes in vasoplegic shock.
AB  - OBJECTIVES: The purpose of this study was to investigate whether patients who
      received methylene blue as treatment for vasoplegia during cardiac surgery with
      cardiopulmonary bypass had decreased morbidity and mortality. DESIGN:
      Retrospective analysis. SETTING: Single tertiary care university hospital.
      PARTICIPANTS: Adult patients who suffered from vasoplegia and underwent all types
      of cardiac surgery with cardiopulmonary bypass at this institution between 2007
      and 2008. INTERVENTIONS: With IRB approval, the authors reviewed the charts of
      the identified patients and divided them into 2 groups based on whether they had
      received methylene blue. Two hundred twenty-six patients were identified who met
      the inclusion criteria for the study. Fifty-seven of these patients had received
      methylene blue for vasoplegia. The authors collected data on preoperative and
      intraoperative variables as well as outcomes. MEASUREMENTS AND MAIN RESULTS: The
      patients who received methylene blue had higher rates of in-hospital mortality, a
      compilation of morbidities, as well as renal failure and hyperbilirubinemia. A
      multiple logistic regression model demonstrated that receiving methylene blue was
      an independent predictor of in-hospital mortality (p value: 0.007, OR 4.26, 95%
      CI: 1.49-12.12), compilation of morbidities (p value: 0.001, OR 4.80, 95% CI:
      1.85-12.43), and hyperbilirubinemia (p value:<0.001, OR 6.58, 95% CI: 2.91
      14.89). Using propensity score matching, the association with morbidity was again
      seen but the association with mortality was not found. CONCLUSIONS: The current
      study identified the use of methylene blue as treatment for vasoplegia to be
      independently associated with poor outcomes. While further studies are required,
      a thorough risk-benefit analysis should be applied before using methylene blue
      and, perhaps, it should be relegated to rescue use and not as first-line therapy.

PMID- 23972740
TI  - Prediction of volume-responsiveness during one-lung ventilation: a comparison of
      static, volumetric, and dynamic parameters of cardiac preload.
AB  - OBJECTIVES: The aim of this study was to evaluate the ability of static,
      volumetric, and dynamic parameters of cardiac preload to predict volume
      responsiveness during one-lung ventilation (OLV). DESIGN: Prospective
      experimental study. SETTING: Laboratory of the animal facility of the University
      Medical Center Hamburg-Eppendorf. PARTICIPANTS: Twenty-three German domestic
      pigs. INTERVENTIONS: Hypovolemia was induced by withdrawing 20 mL/kg body weight
      (BW) of blood. OLV was established, and the volume withdrawn was re-transfused in
      3 volume-loading steps, each consisting of 7 mL/kg BW. An ultrasonic flow probe
      around the pulmonary artery was used to measure the stroke-volume index (SVI) and
      to evaluate the volume response. An increase in the SVI of >= 15% was considered
      a positive response. For each measurement time point, central venous pressure
      (CVP), left atrial pressure (LAP), the global end-diastolic volume index (GEDI),
      stroke-volume variation (SVV), and pulse-pressure variation (PPV) were recorded.
      The ability to predict volume responsiveness was assessed using ROC analysis.
      MEASUREMENTS AND MAIN RESULTS: A total of 69 volume loading steps were performed,
      48 of which showed a positive volume response. ROC analysis revealed the
      following area under the curve (AUC) values: CVP, 0.88; LAP, 0.65; GEDI, 0.75;
      SVV, 0.78; and PPV, 0.83. A comparison of the areas under the ROC curves did not
      reveal any statistically significant differences (p>0.05), with the exception of
      LAP compared with CVP (p = 0.005). CONCLUSIONS: Under these OLV experimental
      conditions, the volumetric and dynamic parameters of preload, as well as CVP,
      seemed to be of similar value in predicting volume responsiveness.

PMID- 23972739
TI  - Arterial hyperoxia during cardiopulmonary bypass and postoperative cognitive
      dysfunction.
AB  - OBJECTIVE: To determine the effect of arterial normobaric hyperoxia during
      cardiopulmonary bypass (CPB) on postoperative neurocognitive function. The
      authors hypothesized that arterial hyperoxia during CPB is associated with
      neurocognitive decline at 6 weeks after cardiac surgery. DESIGN: Retrospective
      study of patients undergoing cardiac surgery with CPB. SETTING: A university
      hospital. PARTICIPANTS: One thousand eighteen patients undergoing coronary artery
      bypass graft (CABG) or CABG + valve surgery with CPB who previously had been
      enrolled in prospective cognitive trials. INTERVENTIONS: A battery of
      neurocognitive measures was administered at baseline and 6 weeks after surgery.
      Anesthetic and surgical care was managed as clinically indicated. MEASUREMENTS
      AND MAIN RESULTS: Arterial hyperoxia was assessed primarily as the area under the
      curve (AUC) for the duration that PaO2 exceeded 200 mmHg during CPB and
      secondarily as the mean PaO2 during bypass, as a PaO2 = 300 mmHg at any point and
      as AUC>150 mmHg. Cognitive change was assessed both as a continuous change score
      and a dichotomous deficit rate. Multivariate regression accounting for age, years
      of education, baseline cognition, date of surgery, baseline postintubation PaO2,
      duration of CPB, and percent change in hematocrit level from baseline to lowest
      level during CPB revealed no significant association between hyperoxia during CPB
      and postoperative neurocognitive function. CONCLUSIONS: Arterial hyperoxia during
      CPB was not associated with neurocognitive decline after 6 weeks in cardiac
      surgical patients.

PMID- 23972741
TI  - Discrepancy between superior vena cava oxygen saturation and mixed venous oxygen
      saturation can predict postoperative complications in cardiac surgery patients.
AB  - OBJECTIVE: To determine if increases in discrepancy between ScvO2 and SvO2 (ScvO2
      - SvO2 = DeltaSO2) during surgery in cardiac surgery patients can predict
      postoperative complications. DESIGN: Prospective, observational study. SETTING:
      University hospital. PARTICIPANTS: One hundred two patients undergoing cardiac
      surgery were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Central venous oxygen saturation (ScvO2) and mixed venous oxygen saturation
      (SvO2) values during surgery automatically were collected. The average value of
      DeltaSO2 for every minute was calculated. The area under the receiver operating
      characteristic curve for prolonged postoperative ICU stay (>=3 days) was 0.745
      for DeltaSO2, which was significantly different from those of ScvO2 and SvO2
      (p<0.05) (ScvO2; 0.584, SvO2; 0.598). The optimal threshold value of DeltaSO2 to
      predict prolonged ICU stay (>=3 days) was 12% (sensitivity: 72.0%, specificity:
      76.9%). Postoperative ICU duration, ventilation time, and hospital stay were
      significantly longer in Group D patients (intraoperative maximum DeltaSO2 >=12%)
      than those in Group N patients (intraoperative maximum DeltaSO2<12%). As for
      postoperative complications, the number of patients with postoperative use of
      intra-aortic balloon pumping, delirium, respiratory failure requiring
      tracheotomy, and severe complications was significantly higher in Group D
      patients. Multivariate logistic regression models were used to evaluate the
      independent effects of perioperative variables on the risk of developing
      prolonged ventilation (>24 hours) and prolonged ICU stay (>=3 days). A
      discrepancy in intraoperative DeltaSO2 was an independent risk factor for
      prolonged postoperative ventilation and ICU stay. CONCLUSION: The discrepancy
      between ScvO2 and SvO2 during cardiac surgery is an independent risk factor of
      postoperative complications such as prolonged ICU stay and ventilation time.

PMID- 23972742
TI  - Particle exposure in a baroque church during Sunday Masses.
AB  - Particle concentrations were measured in a Baroque church during five Sunday
      Masses. The highest particle number and mass concentrations were observed when
      both candles and the incense were burned. They were respectively 16.8 and 14.3
      times higher than outdoors for submicron particles. The exposure to particles
      experienced by the churchgoers, especially priests and church workers who
      participated in several Masses on that day, was considerably higher than the
      exposure experienced at the same time outdoors. 

PMID- 23972743
TI  - Chronic opioid use during pregnancy: maternal and fetal implications.
AB  - Current trends in the United States suggest that chronic narcotic use has
      increased in reproductive aged women over the past 10 years. Regular exposure to
      such substances during pregnancy has maternal and fetal implications. Appropriate
      prenatal care is critical to optimizing outcomes. Management options for narcotic
      dependence should be patient-specific and may include discontinuation of
      narcotics with careful observation, limitation of prescription dispensing, or
      substitution therapy with methadone or buprenorphine. A multidisciplinary,
      collaborative approach is highly recommended. This review discusses usage of
      narcotic medications, associated maternal and fetal risks, and management
      strategies for the antepartum, intrapartum, and postpartum periods. 

PMID- 23972744
TI  - Nonpharmacologic labor analgesia.
AB  - A supportive medical team should be well informed on the various pharmacologic
      and nonpharmacologic modalities of coping with or mitigating labor pain to
      appropriately support and respectfully care for parturients. Using the methodical
      rigor of previously published Cochrane systematic reviews, this summary evaluates
      and discusses the efficacy of nonpharmacologic labor analgesic interventions. 

PMID- 23972745
TI  - Combined spinal-epidural versus epidural analgesia for labor and delivery.
AB  - The rapid onset of analgesia and improved mobility with combined spinal-epidural
      (CSE) techniques has been associated with a higher degree of maternal
      satisfaction compared with conventional epidural analgesia. However, controversy
      exists in that initiation of labor analgesia with a CSE may be associated with an
      increased risk for nonreassuring fetal status (ie, fetal bradycardia) and a
      subsequent need for emergent cesarean delivery. Overall, both epidural and CSE
      techniques possess unique risk/benefit profiles, and the decision to use one
      technique rather than the other should be determined based on individual patient
      and clinical circumstances. 

PMID- 23972746
TI  - The association between epidural labor analgesia and maternal fever.
AB  - The association between epidural labor analgesia and maternal fever is complex
      and controversial. Observational, retrospective, before-and-after, and randomized
      controlled trials all support the association, with the most current evidence
      supporting the mechanistic involvement of noninfectious inflammation. Considering
      the clinically significant neonatal consequences that have been previously
      demonstrated, and the possibility of more common subclinical fetal brain injury
      that animal models imply, the avoidance of maternal fever during labor is
      imperative. With the current popularity of epidural analgesia in labor, it is
      important that clinicians delineate how epidurals cause maternal fever and how to
      block the noninfectious inflammatory response that seems to warm a subset of
      women laboring with epidurals. 

PMID- 23972747
TI  - Anesthetic management of external cephalic version.
AB  - Breech presentation is common at term and its reduction through external cephalic
      version represents a noninvasive opportunity to avoid cesarean delivery and the
      associated maternal morbidity. In addition to uterine relaxants, neuraxial
      anesthesia is associated with increased success of version procedures when
      surgical anesthetic dosing is used. The intervention is likely cost effective
      given the effect size and the avoided high costs of cesarean delivery. 

PMID- 23972748
TI  - Maternal anesthesia for fetal surgery.
AB  - This article describes the anesthetic management of pregnant women undergoing
      fetal surgery. Discussion includes general principles common to all fetal
      surgeries as well as specifics pertaining to open fetal surgery, minimally
      invasive fetal surgery, and ex utero intrapartum therapy (EXIT) procedures. 

PMID- 23972749
TI  - Fetal anesthesia and pain management for intrauterine therapy.
AB  - Anesthesia provision for fetal intervention differs from most other anesthetic
      situations insofar as anesthesiologists must care for 2 or more patients-each
      with potentially conflicting requirements. The first is the mother who can
      readily indicate discomforts, can be monitored directly, and to whom drugs may be
      administered directly and easily. For the fetus (or fetuses), nociception must be
      assumed or inferred indirectly, monitoring is limited at best, and drug
      administration is complicated and often indirect. Fetal and maternal hemodynamic
      stability must be assured; and a plan to resuscitate the fetus, should problems
      occur during the procedure, must be developed. 

PMID- 23972750
TI  - Multimodal postcesarean delivery analgesia.
AB  - Cesarean deliveries can be associated with moderate to severe postoperative pain.
      Appropriate management of pain is important because it results in better patient
      satisfaction, earlier mobilization, and improved maternal-infant bonding. There
      are many individual options for treatment of pain; however, multimodal analgesic
      therapy has become the mainstay of treatment. In this article, the epidemiology
      of postcesarean delivery pain, pain mechanisms, and the multiple options
      available to providers for treatment of postoperative pain are discussed. 

PMID- 23972751
TI  - Assessment of pain in the neonate.
AB  - Accurate pain assessment in preterm and term neonates in the neonatal intensive
      care unit (NICU) is of vital importance because of the high prevalence of painful
      experiences in this population, including both daily procedural pain and
      postoperative pain. Over 40 tools have been developed to assess pain in neonates,
      and each NICU should choose a limited number of pain assessment tools for
      different populations and contexts. Only two pain assessment tools have a metric
      adjustment to account for differences of pain assessment in prematurity. Preterm
      neonates do not display behavior and physiologic indicators of pain as reliably
      and specifically as full term infants, and preterm infants are vulnerable to long
      term sequelae of painful experiences. "Brain-oriented" approaches for more
      objective measurement of pain in neonates may become available in the future. In
      the meantime, neonatal pain assessment tools need to be taught, implemented, and
      their ongoing use optimized to form a consistent, reproducible basis for the safe
      and effective treatment of neonatal pain. 

PMID- 23972752
TI  - Biological and neurodevelopmental implications of neonatal pain.
AB  - Nociceptive pathways are functional following birth. In addition to physiological
      and behavioral responses, neurophysiological measures and neuroimaging evaluate
      nociceptive pathway function and quantify responses to noxious stimuli in preterm
      and term neonates. Intensive care and surgery can expose neonates to painful
      stimuli when the developing nervous system is sensitive to changing input,
      resulting in persistent impacts into later childhood. Early pain experience has
      been correlated with increased sensitivity to subsequent painful stimuli,
      impaired neurodevelopmental outcomes, and structural changes in brain
      development. Parallel preclinical studies have elucidated underlying mechanisms
      and evaluate preventive strategies to inform future clinical trials. 

PMID- 23972753
TI  - Nonpharmacological management of pain during common needle puncture procedures in
      infants: current research evidence and practical considerations.
AB  - All infants undergo painful procedures involving skin puncture as part of routine
      medical care. Pain from needle puncture procedures is suboptimally managed.
      Numerous nonpharmacologic interventions are available for these painful
      procedures, including swaddling, holding, skin-to-skin care, pacifier, sweet
      tasting solutions, and breast-feeding. Adoption of nonpharmacologic pain
      relieving interventions into routine clinical practice is feasible and should be
      a standard of care in the delivery of quality health care for infants. This
      review summarizes current knowledge about the epidemiology of pain from common
      needle puncture procedures in infants, the effectiveness of nonpharmacologic
      interventions, implementation considerations, and unanswered questions for future
      research. 

PMID- 23972754
TI  - Management of neonatal abstinence syndrome from opioids.
AB  - Most infants at risk for neonatal abstinence syndrome have opioid plus another
      drug exposure; polypharmacy is the rule rather than the exception. Scales for
      evaluation of neonatal abstinence syndrome are primarily based for opioid
      withdrawal. A standard protocol to treat neonatal abstinence syndrome has not
      been developed. Institute nonpharmacologic strategies for all neonates at risk.
      The American Academy of Pediatrics recommends mechanism-directed therapy (treat
      opioid withdrawal with an opioid) as the first-line therapy. Second-line
      medications are currently under evaluation. 

PMID- 23972755
TI  - Regional anesthesia in neonates and infants.
AB  - Optimal pain management can significantly impact the surgical outcome and length
      of stay in the neonatal intensive care unit (NICU). Regional anesthesia is an
      effective alternative that can be used in both term and preterm neonates. A
      variety of neuraxial and peripheral nerve blocks have been used for specific
      surgical and NICU procedures. Ultrasound guidance has increased the feasibility
      of using these techniques in neonates. Education and training staff in the use of
      continuous epidural infusions are important prerequisites for successful
      implementation of regional anesthesia in NICU management protocols. 

PMID- 23972756
TI  - Sedation and analgesia to facilitate mechanical ventilation.
AB  - Regardless of age, health care professionals have a professional and ethical
      obligation to provide safe and effective analgesia to patients undergoing painful
      procedures. Historically, newborns, particularly premature and sick infants, have
      been undertreated for pain. Intubation of the trachea and mechanical ventilation
      are ubiquitous painful procedures in the neonatal intensive care unit that are
      poorly assessed and treated. The authors review the use of sedation and analgesia
      to facilitate endotracheal tube placement and mechanical ventilation.
      Controversies regarding possible adverse neurodevelopmental outcomes after
      sedative and anesthetic exposure and in the failure to treat pain is also
      discussed. 

PMID- 23972757
TI  - Neurodevelopmental implications of the use of sedation and analgesia in neonates.
AB  - Laboratory studies have shown that general anesthetics may cause accelerated
      apoptosis and other adverse morphologic changes in neurons of the developing
      brain. The mechanism may be related to the neuronal quiescence or inactivity
      associated with anesthetic exposure. Few data exist on how brief anesthetic
      exposure may affect neurodevelopment in the newborn. Good evidence however shows
      that untreated pain and stress have an adverse effect on neurodevelopment, and
      therefore, at this stage, providing effective analgesia, sedation, and anesthesia
      would seem to be more important than concern over neurotoxicity. 

PMID- 23972758
TI  - Genetic contributions to labor pain and progress.
AB  - Studies on genetic contributions to labor analgesia have essentially evaluated
      the MU-opioid receptor gene (OPRM1), with some evidence that p.118A/G of OPRM1
      influences the response to neuraxial opioids. As for labor progress, the beta2
      adrenergic receptor gene (ADRB2) is associated with preterm labor and delivery,
      and impacts the course of labor. Taken together though, there is no evidence that
      pharmacogenetic testing is needed or beneficial in the context of obstetric
      anesthesia; however, realizing the influence of genetic variants on specific
      phenotypes provides the rationale for a more cautious interpretation of clinical
      studies that attempt to find a dose-regimen that fits all. 

PMID- 23972759
TI  - Painful truths about newborn pain management.

PMID- 23972760
TI  - Pain management in the perinatal period.

PMID- 23972761
TI  - Olfactory perceptual abnormality associated with vitamin B12 deficiency.

PMID- 23972762
TI  - The benefits of EVAR planning using a 3D workstation.
AB  - OBJECTIVES: To evaluate the influence of planning endovascular aneurysm repair
      (EVAR) with a three-dimensional (3D) workstation on early and midterm outcomes.
      METHODS: All patients undergoing infrarenal EVAR performed between 2006 and 2009
      at our institution were included in the current study. Prior to 2008 (group 1),
      endograft sizing was performed by interrogation of computed tomography
      angiography axial images. After 2008 (group 2), endograft sizing was routinely
      performed using a 3D workstation (Aquarius, Terarecon), allowing for multiplanar
      reconstruction and centerline analysis. Pre-, peri-, postoperative, and follow-up
      data were prospectively entered in an electronic database. All postoperative
      complications and subsequent secondary interventions depicted during the 2-year
      period following EVAR were compared. Secondary intervention and mortality rates
      were defined at 2 years and compared. Freedom from secondary intervention and
      overall survival rates were calculated using the Kaplan-Meier method during
      follow-up and compared by log-rank test. RESULTS: A total of 295 patients (149
      patients in group 1 and 146 patients in group 2) were included. All patients had
      completed a minimum of 2 years of follow-up. During this 2-year period following
      EVAR, the type 1 endoleak rate was 8.7% in group 1 and 1.4% in group 2 (p = .004)
      respectively. Secondary intervention rates related to type 1 endoleak was 5.4% in
      group 1 and 0 in group 2 (p < .001). No difference was observed regarding all
      cause mortality, aneurysm-related death, and freedom from secondary intervention
      rates during follow-up. CONCLUSION: The routine use of 3D workstations for EVAR
      planning significantly reduces the rate of type 1 endoleaks and, therefore, the
      rate of related secondary interventions.

PMID- 23972763
TI  - Cloning, expression and characterization of a putative 7alpha-hydroxysteroid
      dehydrogenase in Comamonas testosteroni.
AB  - The short-chain dehydrogenase/reductase (SDR) superfamily is a large and diverse
      group of genes with members found in all forms of life. Comamonas testosteroni
      (C. testosterone) ATCC11996 is a Gram-negative bacterium which can use steroids
      as carbon and energy source. In the present investigation, we found a novel SDR
      gene 7alpha-hydroxysteroid dehydrogenase (7alpha-HSD) which is located 11.9 kb
      upstream from hsdA with the same transcription orientation in the C. testosteroni
      genome. The open reading frame of this putative 7alpha-hydroxysteroid
      dehydrogenase gene consists of 771 bp and translates into a protein of 256 amino
      acids. Two consensus sequences of the SDR superfamily were found, an N-terminal
      Gly-X-X-X-Gly-X-Gly cofactor-binding motif and a Tyr-X-X-X-Lys segment (residues
      161-165 in the 7alpha-HSD sequence) essential for catalytic activity of SDR
      proteins. To produce purified 7alpha-HSD protein, the 7alpha-HSD gene was cloned
      into plasmid p(ET-15b) and the over expressed protein was purified by His-tag
      sequence on metal chelate chromatography. To prove that 7alpha-HSD is involved in
      the metabolic pathway of steroid compounds, we constructed a 7alpha-HSD knock-out
      mutant of C. testosteroni. Compared to the wild type C. testosteroni, degradation
      of testosterone, estradiol and cholesterol were decreased in the 7alpha-HSD knock
      out mutant. Furthermore, growth in the medium with testosterone, estradiol and
      cholesterol was impaired in 7alpha-HSD knock-out mutant. The results showed that
      7alpha-HSD is involved in steroid degradation.

PMID- 23972764
TI  - An overview of the management of adult ependymomas with emphasis on relapsed
      disease.
AB  - Ependymomas are rare neoplasms of the central nervous system. Disease-free
      survival after relapse is poor and approaches to treatment in recurrent disease
      often palliative. This overview summarises the management of primary disease for
      which broad consensus exists. We also extensively review treatment options in
      relapsed disease for which approaches to treatment are varied due to the paucity
      of literature evidence. Incorporated in this overview is a survey of UK neuro
      oncology units to form a snapshot of current UK practise with respect to
      preferred systemic therapy regimens for patients with recurrent ependymoma. The
      outcome reflects a preference for mainly oral-based regimens. Universal guidance
      is lacking in the management of non-operable irradiated recurrent ependymoma and
      there are worthy therapeutic avenues for further investigation, in particular the
      role of radical re-irradiation and also the potential of bevacizumab in advanced
      disease. It is hoped that advances can be achieved by multicentre collaboration
      in future studies to overcome the difficulties posed by achieving meaningful data
      in such a rare tumour with extensive natural history. 

PMID- 23972766
TI  - Pathways to similar executive impairment: comparison of schizophrenia patients
      and healthy aging individuals.
AB  - Executive impairment is prominent in schizophrenia, in conditions such as
      Parkinson's disease and dementia and in healthy aging. Identifying processes that
      critically constrain executive function can advance investigation of their
      biological basis and treatment planning. Recent findings that elderly healthy
      individuals showed similar impairment on conditional exclusion task as
      schizophrenia patients raised the question whether similar processes are
      impaired. To test this we compared 56 schizophrenia patients, 57 elderly and 77
      young healthy individuals on three executive tests: conditional exclusion,
      abstraction and inhibition and tests of working memory and psychomotor speed.
      Schizophrenia patients performed worse than elderly healthy on abstraction,
      inhibition and verbal working memory. They were similarly impaired on Penn
      Conditional Exclusion Test (PCET) outcome measures but differed in performance
      characteristics. Schizophrenia patients needed relatively more trials to learn
      the first PCET category than the second or the third. This correlated with other
      cognitive impairments, particularly in working memory. Elderly healthy
      individuals found it most difficult to learn the last category. The two groups
      showed different error patterns. We propose that schizophrenia patients have
      particular difficulty in early (probabilistic) learning ("what to do") while
      aging individuals have selective impairment in executive integration. These
      constitute distinct targets for customized treatment in the two conditions. 

PMID- 23972765
TI  - When knowing what to do is not sufficient to make good decisions: deficient use
      of explicit understanding in remitted patients with histories of suicidal acts.
AB  - Disadvantageous decision-making has been reported in patients who had attempted
      suicide and may represent a cognitive risk factor for suicide. Making decisions
      necessitates both implicit/associative and explicit/analytic processes. Here, we
      explored explicit mechanisms, and hypothesized that suicide attempters fail to
      use explicit understanding to make favorable choices. The Iowa Gambling Task
      (IGT) was used to assess decision-making in 151 non-depressed patients with a
      history of mood disorder and suicidal act, 81 non-depressed patients with a
      history of mood disorders but no suicidal act, and 144 healthy individuals. After
      performing the task, we assessed the explicit understanding of the participants
      of the contingencies in the task, i.e. which options yielded higher gain or loss.
      Correct explicit understanding was reported less often in suicide attempters and
      affective controls than in healthy controls (45.7% and 42.0% vs. 66.0%).
      Moreover, understanding was associated with better performance in healthy and
      affective controls, but not in suicide attempters, with no between-group
      difference among those who did not reach understanding. Patients with histories
      of suicide attempt, therefore, show a disconnection between what they "know" and
      what they "do", possibly reflecting underlying impairments in implicit
      associative processes. These cognitive alterations should be addressed in
      preventative interventions targeting suicide. 

PMID- 23972767
TI  - Molecular characterisation and infection dynamics of Dentitruncus truttae from
      trout (Salmo trutta and Oncorhynchus mykiss) in Krka River, Croatia.
AB  - Dentitruncus truttae (Acanthocephala, Palaeacanthocephala) is an intestinal
      parasite of fish that can cause extensive damage to the host digestive tract, yet
      little is known about its epidemiology and genetic variability. It is a member of
      the Illiosentidae family with a worldwide distribution restricted to parts of
      southeast Europe. Its usual host is brown trout (Salmo trutta), but we report
      here the first detection in the intestine of rainbow trout (Oncorhynchus mykiss).
      We examined the physiology of D. truttae-infected S. trutta and O. mykiss,
      seasonal and spatial variability of D. truttae infections, and genetic
      variability of the parasite population in Krka River, Croatia. D. truttae was
      more abundant in both trout populations in the autumn, with no seasonal variation
      in prevalence. The parasite was more abundant in male than female trout (n=75,
      p<0.01). Analysis of the spatial distribution of the parasite across various
      sampling sites along the river showed the lowest prevalence and abundance of
      parasitic infections at the most downstream sampling site, which may reflect the
      predominance of female fish there and/or the smaller population of intermediate
      hosts. To provide the first molecular insights into D. truttae, we analysed
      sequences at three marker loci: the 18S rRNA gene, the cytochrome c oxidase
      subunit 1 (COI) gene and the internal transcribed spacer region. Phylogenetic
      analysis based on 18S rRNA confirmed the taxonomic grouping of D. truttae in the
      Illiosentidae family, first made more than 50 years ago based on morphology. The
      COI haplotype network did not show discrete genetic clusters corresponding to the
      different sampling sites, suggesting a stable population. These insights into D.
      truttae haplotype frequency distribution and intrapopulation genetic variation
      revealed minimal genetic variability, compared to the other acanthocephalan
      species.

PMID- 23972768
TI  - Development and evaluation of a loop-mediated isothermal amplification assay for
      rapid detection of Leishmania infantum in canine leishmaniasis based on cysteine
      protease B genes.
AB  - We developed a Leishmania infantum specific LAMP assay that was carried out using
      a set of, six primers targeting the cysteine protease B multi copy gene of L.
      infantum. Our result shows that we, successfully detect the L. infantum DNA and
      that amplification is specific as no cross reaction was seen, with L. major, L.
      tropica, L. turanica, L. aethiopica, L. tarentolae, L. gerbilii, Trypanosoma
      cruzi or, human genomic DNA. When compared to conventional cpb based PCR, the
      sensitivity of LAMP assay, was higher with a detection limit of 50 fg/MUl of
      genomic L. infantum parasite DNA. Accurate and rapid, diagnosis of canine
      leishmaniasis (CanL) is an important issue that allows early treatment and,
      prevents transmission. Our developed LAMP assay was used to evaluate occurrences
      of Leishmania infantum in seventy five (75) dogs from the field. Blood samples
      were used to perform LAMP assay, classical PCR, IFAT and microscopy that was used
      as gold standard. The IFAT in addition to, microscopy, are the basic techniques
      used for CanL diagnosis at the School of Veterinary Medicine, where we obtained
      our samples. Compared to molecular methods, the serology (IFAT) test shows the,
      best sensitivity (88.57%) with, however, a much lower specificity (52.5%) due to
      a relatively high, number of false-positive results (22 animals). The PCR assay
      shows a low sensitivity (37.14%) and, specificity around (82.5%). Our LAMP assay
      shows a suitable sensitivity (54%) and a good specificity, (80%), with however,
      positive (70%) and negative (66%) predictive values. Furthermore, the best,
      positive likelihood ratio (LR+) was obtained by LAMP assay (2.7). This technique
      presents the highest, kappa value (with a fair agreement of 0.34). Moreover, the
      relative stability of the reagents indicates, that LAMP may be a good alternative
      to a conventional PCR, especially under field conditions. Finally in, a brief
      cost evaluation, the LAMP assay compares favorably with other molecular
      diagnostic tests. This, is the first study that evaluates the L. infantum
      specific LAMP alongside other diagnostics tools for, CanL. Our results indicate a
      suitable sensitivity and specificity for the developed LAMP assay that could, has
      usefulness application on dogs and human L. infantum diagnosis.

PMID- 23972769
TI  - [Balloon catheter for cervical ripening on scarred uterus with unfavorable
      cervix: multicenter retrospective study of 151 patients].
AB  - OBJECTIVES: To evaluate safety and efficacy of balloon catheter for labor
      induction in women with previous cesarean section. MATERIAL AND METHODS: In a
      multicenter retrospective cohort study, 151 patients were included with the
      following criteria: pregnancy over 37 weeks, singleton, vertex presentation,
      previous caesarean section with unique transversal segmentary incision, medical
      indication for induction of labor, unfavorable cervix with Bishop score inferior
      to 7, no premature rupture of membranes. Balloon catheter used for cervix
      ripening, is inflated from 30 to 80 mL of sterile of NaCl and is left until 24
      hours. RESULTS: Overall rate of vaginal delivery was 53.7% (81/151). Labor began
      before balloon catheter removal for 58 out of 151 (38.4%) with vaginal delivery
      for 75% (42/58). Best prognosis factors for vaginal delivery were spontaneous
      labor after balloon removal (P=0.004) and anterior vaginal delivery (P=0.03).
      Side effects were rare bleeding or PROM, but didn't prevent continuing ripening
      labor. Other morbidity consisted in two uterus ruptures (1.2%) without
      maternofetal incidence. CONCLUSION: Supracervical balloon is a safe and
      efficiency method for inducing labor on scarred uterus with unfavorable cervix
      with low side effects.

PMID- 23972770
TI  - [About the article by L. Rossard et al. (2013;42(5):480-7): "Cervical ripening
      with balloon catheter for scarred uterus: a three-year retrospective study"].

PMID- 23972771
TI  - [Become a obstetrician-gynecologist after 5 years of internship: between dream,
      reality and illusion].

PMID- 23972772
TI  - [Obstetric data in a population with postural changes during labor and delivery].
AB  - INTRODUCTION: The aim of this study was to describe the potential impact of an
      active birth on classical obstetrical outcomes, as labor duration, cesarean
      section rate, couples and team satisfactions. MATERIAL AND METHODS: This
      observational study was prospective, monocentric and took place between May 2007
      and February 2009 at the maternity ward of the University Hospital of Caen,
      France. An "active birth" was defined as an active latent-phase (having a change
      in position and/or a bath and/or a walk) followed by at least three changes in
      position during the active phase. The suggested positions were: lateral or dorsal
      decubitus, ROSA, on all fours, seated, standing and crouch. A position must have
      lasted at least 20 minutes to be considered. RESULTS: Out of the 1906 women
      included, 828 had an active birth (43.4%). Due to our definition of an "active
      birth", a "non-active birth" was significantly associated with a quicker labor.
      An "active birth" was associated with a decreased rate of cesarean section
      (OR=0.71; IC95%=[0.51-0.99]). The parturients satisfaction median was 9 on a
      scale of 0 to 10, the spouses'one was 10. Midwives were more satisfied when it
      was an "active birth". CONCLUSION: Significant associations with active births
      were highlighted, which would require to be validated by a randomised study. This
      practise plenty satisfied couples and midwives. In fact, no litterature exists to
      date. A consensus about the definition of an active birth is still necessary in
      order to lead to guidelines.

PMID- 23972773
TI  - [Decidualization of ovarian endometriosis during pregnancy mimicking malignancy:
      a difficult diagnosis].

PMID- 23972774
TI  - [Maternal refusal to consent to a cesarean delivery, stillbirth].
AB  - The doctor-lawyer perspective that we discuss is a maternal refusal to consent to
      a cesarean delivery for a fetal indication in June 2011. Despite repeated
      information of the risks during a three-week hospitalization for pre-eclampsia,
      after being assured of the proper understanding of the seriousness of the
      situation by the patient and spouse, and after consideration to transfer to
      another hospital, the reiterated refusal led to a late fetal extraction resulting
      in term stillbirth.

PMID- 23972775
TI  - [Correlation between the perineal-to-skull measurement by tranperineal
      ultrasound, failure of vaginal operative delivery and maternal-fetal morbidity].
AB  - OBJECTIVES: To assess the influence of the perineal-to-skull measurement by
      tranperineal ultrasound (TPU) on the outcome of vaginal operative extraction
      together with maternal and fetal morbidity. MATERIALS AND METHODS: Retrospective,
      monocentric and descriptive study was done on 272 patients, from 2009 January 1st
      to 2009 December 31st. It compares the failure rate of instrumental extraction,
      total caesarean section rate together with the maternal morbidity (type of
      perineal tears and post-partum hemorrhage rate) and fetal morbidity (5' Apgar
      score, arterial pH, transfer in neonatal intensive care unit) to the values
      obtained with TPU. RESULTS: There is a correlation between the perineal-to-skull
      measurements higher or equal to 50mm at TPU and the instrumental failure rate
      (<50mm 0.8% vs. >=50mm 11.9%; P<0.0001), caesarean (0.9% vs. 33.3%; P<0.0001),
      post-partum haemorrhage (3% vs. 11.9%; P=0.02), et paediatric intervention (16.7%
      vs. 31%; P=0.03). CONCLUSION: Perineal-to-skull distance measured with TPU higher
      or equal to 50mm is at risk of instrumental failure and maternal morbidity.
      Associated with clinical examination and usual obstetrical risk factors, TPU
      could be useful to the decision between operative vaginal delivery and
      prophylactic caesarean section.

PMID- 23972776
TI  - [Preliminary study on the feasibility of robot-assisted double mesh
      sacrocolpopexy in comparison to the laparoscopic approach].
AB  - OBJECTIVES: The aim of our study was to demonstrate the feasibility of the
      laparoscopic robot-assisted anterior and posterior mesh sacrocolpopexy compared
      to the laparoscopic approach. MATERIALS AND METHODS: Between November 2009 and
      August 2011, 36 women underwent sacrocolpopexy with anterior and posterior mesh,
      16 by a robot-assisted approach and 20 by laparoscopy. The cases were
      systematically evaluated at 1 and 12 months postoperatively. All cases were
      contacted 6 months later to evaluate the functional results. RESULTS: Both groups
      were comparable in terms of age, ASA score, Body Mass Index, surgical history and
      grades of pelvic organ prolapse preoperatively. There was no difference in terms
      of hospital stay, per- and postoperative complications, especially concerning the
      rate of postoperative constipation. The mean operating time was significantly
      more important in the Robot group (P=0.001) with 318 min for the Robot group
      versus 260 min for the laparoscopic group. With a mean follow-up of 12 months,
      the anatomic result was satisfactory without recurrence in 97.2% of the cases.
      The urinary and sexual results, the restart of a sexual activity postoperatively,
      the surgical satisfaction and the return to daily activities were comparable
      between both groups. CONCLUSION: Robot-assisted laparoscopic sacrocolpopexy seems
      to be a reliable technique with morbidity, anatomic and functional outcomes
      comparable to that of laparoscopy.

PMID- 23972777
TI  - Three different bacterial detection systems for platelet concentrates under inter
      laboratory conditions.
AB  - BACKGROUND: A variety of screening methods are currently used worldwide in order
      to decrease the risk of transfusion-transmitted sepsis and improve the safety of
      PCs. METHODS/MATERIALS: PCs inoculated with five different transfusion-relevant
      species of bacteria at concentrations of 1, 10, and 100 colony-forming units
      (CFU)ml(-1) were stored at 22 degrees C for 7 days. Flow cytometry (FACS),
      BacT/Alert automated culturing, and a quantitative real-time PCR (Q-PCR) were
      then used to detect the presence of bacteria in samples prepared from these PCs.
      RESULTS: At the initial spiking concentrations of 1, 10, and 100 CFU ml(-1), Q
      PCR detected all five bacterial species tested. Screening with the BacT/Alert
      culture-based system allowed bacterial detection (inoculated on day 0) within a
      mean time of 15.13 h for all three spiking concentrations. Using FACS, positive
      signals were obtained for all three concentrations of Escherichia coli and
      Bacillus cereus on day 1 and for initial spiking concentrations of Pseudomonas
      aeruginosa and Staphylococcus aureus of 1 CFU ml(-1) on day 2. For Staphylococcus
      epidermidis, detection of an initial inoculum of 1 CFU ml(-1) was possible only
      beginning on day 6. CONCLUSION: This study shows that under standard laboratory
      conditions the sensitivity of FACS in the detection of bacterial contamination of
      PCs was lower than that of either the BacT/Alert automated culturing method or Q
      PCR.

PMID- 23972778
TI  - Generalized periodic epileptiform discharges in critically ill children: clinical
      features, and outcome.
AB  - PURPOSE: Generalized periodic epileptiform discharges (GPDs) are a specific
      periodic EEG pattern, reported as having a poor clinical outcome. The incidence
      and clinical implications of this EEG pattern in children are not known. In this
      study, we examined the clinical features of children with GPDs. METHODS: EEG
      video monitoring reports of children with critical illness in the intensive care
      unit were retrospectively reviewed to detect GPDs. The clinical history, hospital
      course and seizure characteristics were reviewed and outcome was based on the
      clinical findings at hospital discharge. RESULTS: Twenty one children (age 2-18
      years) were identified with GPDs. The most common underlying etiology was
      encephalitis (N=11). At the time of EEG, a continuous intravenous infusion (cIV)
      of an anticonvulsant drug was used to treat refractory status epilepticus (RSE).
      Non-convulsive seizures (NCS) were identified in 15, and clinical seizures in 13
      children after GPDs were detected. GPDs occurred after a dose reduction in the
      cIV in 43%. Neuroimaging done in 16 children showed an acute change in 13/16
      (81%) and chronic changes in 2/16 (13%). Five children (23%) died. Seven (33%)
      children had a favorable outcome, whereas the remaining children had a moderate
      to severe disability at the time of hospital discharge. CONCLUSION: GPDs are seen
      during the course of RSE in critically ill children and are associated with
      seizure recurrence. A lower mortality rate occurs in children with GPDs compared
      to adult counterparts, likely related to different etiologies. Although the
      significance of GPDs must be determined within the context of the clinical
      situation, GPDs suggest a still active epileptic process.

PMID- 23972779
TI  - The imaging characteristics of odontogenic myxoma and a comparison of three
      different imaging modalities.
AB  - OBJECTIVE: To report the imaging characteristics of odontogenic myxoma (OM) and
      compare the different imaging modalities used. STUDY DESIGN: The radiological
      images of 33 OM cases were retrospectively analyzed. The radiographs were
      severally examined to describe the features of OM as seen on conventional
      radiographs (CRs), computed tomography (CT) scans, and magnetic resonance images
      (MRIs). RESULTS: MRI was effective in displaying the true extension and contents
      of OMs. CT scans demonstrated the extensions of OMs, expansion, growth pattern,
      and rendered it possible to compare density of OM with that of surrounding
      muscles. Assessment of CRs revealed great limitations about the diagnostic values
      and failed to display important features. CONCLUSIONS: All 3 radiographic
      techniques, conventional radiography, CT, and magnetic resonance imaging (MRI),
      have inherent advantages and disadvantages; however, all 3 should be routinely
      used in the diagnosis of OM. The results of CT and MRI can accurately reveal
      margins of tumors and greatly aid in diagnosis.

PMID- 23972780
TI  - A closer look at the "Protopithecus" fossil assemblages: new genus and species
      from Bahia, Brazil.
AB  - The recently extinct large-bodied New World monkey Protopithecus brasiliensis
      Lund 1836 was named based on a distal humerus and proximal femur found in the
      Lagoa Santa cave system in the southeastern Brazilian state of Minas Gerais.
      These bones are from an animal about twice the size of the largest extant
      platyrrhines. One hundred and seventy-five years later, a nearly complete
      skeleton was discovered in the Toca da Boa Vista caves in the neighboring state
      of Bahia and was allocated to the same taxon as it was the first platyrrhine
      fossil of comparable size found since the originals. Our detailed study of the
      equivalent elements, however, reveals important morphological differences that do
      not correspond to intraspecific variation as we know it in related platyrrhine
      taxa. The presence of both an expanded brachioradialis flange on the humerus and
      gluteal tuberosity on the femur of the Bahian skeleton distinguishes it from the
      Lagoa Santa fossil as well as from all other platyrrhines. Further cranial and
      postcranial evidence suggests a closer relationship of the former with the
      alouattine Alouatta, while the limited Lund material fits more comfortably with
      the ateline clade. Therefore, we propose to limit P. brasiliensis Lund to the
      distal humerus and proximal femur from Lagoa Santa and erect a new genus and
      species for the skeleton from Toca da Boa Vista. Cartelles coimbrafilhoi was a
      large-bodied frugivore with a relatively small brain and diverse locomotor
      repertoire including both suspension and climbing that expands the range of
      platyrrhine biodiversity beyond the dimensions of the living neotropical
      primates. 

PMID- 23972781
TI  - Unexplained pulmonary hypertension in peritoneal dialysis and hemodialysis
      patients.

PMID- 23972782
TI  - Impact factor 0.562--the ultimate goal or the next step forward?

PMID- 23972783
TI  - Who was Harriet Lane?

PMID- 23972784
TI  - NAPNAP research agenda revisions: preliminary survey results.

PMID- 23972785
TI  - Intraoperative neurophysiologic monitoring in spine surgery. Developments and
      state of the art in France in 2011.
AB  - Intraoperative spinal cord monitoring consists in a subcontinuous evaluation of
      spinal cord sensory-motor functions and allows the reduction the incidence of
      neurological complications resulting from spinal surgery. A combination of
      techniques is used: somatosensory evoked potentials (SSEP), motor evoked
      potentials (MEP), neurogenic motor evoked potentials (NMEP), D waves, and
      pedicular screw testing. In absence of intraoperative neurophysiological testing,
      the intraoperative wake-up test is a true form of monitoring even if its latency
      long and its precision variable. A 2011 survey of 117 French spinal surgeons
      showed that only 36% had neurophysiological monitoring available (public
      healthcare facilities, 42%; private facilities, 27%). Monitoring can be performed
      by a neurophysiologist in the operating room, remotely using a network, or
      directly by the surgeon. Intraoperative alerts allow real-time diagnosis of
      impending neurological injury. Use of spinal electrodes, moved along the
      medullary canal, can determine the lesion level (NMEP, D waves). The response to
      a monitoring alert should take into account the phase of the surgical
      intervention and does not systematically lead to interruption of the
      intervention. Multimodal intraoperative monitoring, in presence of a
      neurophysiologist, in collaboration with the anesthesiologist, is the most
      reliable technique available. However, no monitoring technique can predict a
      delayed-onset paraplegia that appears after the end of surgery. In cases of
      preexisting neurological deficit, monitoring contributes little. Monitoring of
      the L1-L4 spinal roots also shows low reliability. Therefore, monitoring has no
      indication in discal and degenerative surgery of the spinal surgery. However,
      testing pedicular screws can be useful. All in all, thoracic and thoracolumbar
      vertebral deviations, with normal preoperative neurological examination are
      currently the essential indication for spinal cord monitoring. Its absence in
      this indication is a lost opportunity for the patient. If neurophysiological
      means are not available, intraoperative wake-up test is a minimal obligation. 

PMID- 23972786
TI  - The incidence of urea cycle disorders.
AB  - A key question for urea cycle disorders is their incidence. In the United States
      two UCDs, argininosuccinic synthetase and lyase deficiency, are currently
      detected by newborn screening. We used newborn screening data on over 6million
      births and data from the large US and European longitudinal registries to
      determine how common these conditions are. The incidence for the United States is
      predicted to be 1 urea cycle disorder patient for every 35,000 births presenting
      about 113 new patients per year across all age groups. 

PMID- 23972787
TI  - Validity of the Patient Health Questionnaire-9 for depression screening and
      diagnosis in East Africa.
AB  - Depression is often underdiagnosed and undertreated in primary care settings,
      particularly in developing countries. This is, in part, due to challenges
      resulting from lack of skilled mental health workers, stigma associated with
      mental illness, and lack of cross-culturally validated screening instruments. We
      conducted this study to evaluate the reliability and validity of the Patient
      Health Questionnaire-9 (PHQ-9) as a screen for diagnosing major depressive
      disorder among adults in Ethiopia, the second most populous country in sub
      Saharan Africa. A total of 926 adults attending outpatient departments in a major
      referral hospital in Ethiopia participated in this study. We assessed criterion
      validity and performance characteristics against an independent, blinded, and
      psychiatrist administered semi-structured Schedules for Clinical Assessment in
      Neuropsychiatry (SCAN) interview. Overall, the PHQ-9 items showed good internal
      (Cronbach's alpha=0.81) and test re-test reliability (intraclass correlation
      coefficient=0.92). A factor analysis confirmed a one-factor structure. Receiver
      Operating Characteristics (ROC) analysis showed that a PHQ-9 threshold score of
      10 offered optimal discriminatory power with respect to diagnosis of major
      depressive disorder via the clinical interview (sensitivity=86% and
      specificity=67%). The PHQ-9 appears to be a reliable and valid instrument that
      may be used to diagnose major depressive disorders among Ethiopian adults. 

PMID- 23972788
TI  - Genetic polymorphisms in the PACAP and PAC1 receptor genes and treatment response
      to venlafaxine XR in generalized anxiety disorder.
AB  - The pituitary adenylate cyclase-activating peptide (PACAP) and its receptor
      (PAC1) are involved in stress response and anxiety. Genotypes for PACAP/PAC1 were
      examined for effects on treatment response to venlafaxine XR in generalized
      anxiety disorder. The Asp54Gly (rs2856966) variant in the PACAP gene was
      associated with better treatment outcome. 

PMID- 23972790
TI  - Transformation products and reaction pathways of carbamazepine during
      photocatalytic and sonophotocatalytic treatment.
AB  - This study examines the degradation of the antiepileptic carbamazepine (CBZ) by
      sonolysis, TiO2-based heterogeneous photocatalysis under UV-A and simulated solar
      irradiation, and by the combined use of UV-A and ultrasound irradiation (i.e.
      sonophotocatalysis) in demineralized water, ground water and effluent wastewater.
      The processes were compared with respect to substrate conversion rate and the
      extent of DOC reduction as a measure of mineralization. CBZ was degraded
      following a pseudo-first order kinetics. Sonophotocatalysis provided the highest
      rate of CBZ transformation over the time-course of the experiment while the
      degree of DOC removal in pure water was similar for all the studied treatments
      (around 40%), and always lower than CBZ conversion. This indicated that a
      considerable organic load remained in the treated solutions that could also be
      attributed to the presence of persistent oxidation products. UPLC-(+ESI)-QToF-MS
      was employed to determine major CBZ-related transformation products. Several
      recalcitrant hydroxy- and keto-derivatives of CBZ were tentatively identified. A
      Daphnia magna bioassay was used to evaluate the potential toxicity of the samples
      collected at different time points showing that the mixtures were highly toxic to
      D. magna.

PMID- 23972789
TI  - Relationship between maladaptive cognitions about sleep and recovery in patients
      with borderline personality disorder.
AB  - Borderline personality disorder (BPD) has been associated with maladaptive
      cognitive processes including dysfunctional attitudes and a negative attribution
      style. Comorbid insomnia affects the course of multiple psychiatric disorders,
      and has been associated with the absence of recovery from BPD. Because
      dysfunctional beliefs and attitudes are common among patients with insomnia, the
      purpose of this study was to evaluate the association between maladaptive sleep
      related cognitions and recovery status (symptomatic remission plus good
      concurrent psychosocial functioning) in patients with BPD. Two hundred and twenty
      three BPD patients participating in the McLean Study of Adult Development (MSAD)
      were administered the Dysfunctional Beliefs and Attitudes about Sleep
      questionnaire (DBAS-16) as part of the 16-year follow-up wave. Maladaptive sleep
      cognitions were compared between recovered (n=105) and non-recovered (n=118) BPD
      participants, in analyses that adjusted for age, sex, depression, anxiety, and
      primary sleep disorders. Results demonstrated that non-recovered BPD patients had
      significantly more severe maladaptive sleep-related cognitions as measured by the
      overall DBAS-16 score. These results demonstrate an association between
      dysfunctional beliefs and attitudes about sleep and recovery status among BPD
      patients. Further research is warranted to evaluate treatments targeted towards
      maladaptive sleep-related cognitions, and their subsequent effects on the course
      of BPD. 

PMID- 23972791
TI  - Estrogen receptor alpha augments changes in hemostatic gene expression in HepG2
      cells treated with estradiol and phytoestrogens.
AB  - Phytoestrogens are popular alternatives to estrogen therapy however their effects
      on hemostasis in post-menopausal women are unknown. The aim of this study was to
      determine the effect of the phytoestrogens, genistein, daidzein and equol on the
      expression of key genes from the hemostatic system in human hepatocyte cell
      models and to determine the role of estrogen receptors in mediating any response
      seen. HepG2 cells and Hep89 cells (expressing estrogen receptor alpha (ERalpha))
      were incubated for 24 h with 50 nM 17beta-estradiol, genistein, daidzein or
      equol. Tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI
      1), Factor VII, fibrinogen gamma, protein C and protein S mRNA expression were
      determined using TaqMan PCR. Genistein and equol increased tPA and PAI-1
      expression in Hep89 cells with fold changes greater than those observed for
      estradiol. In HepG2 cells (which do not express ERalpha), PAI-1 and tPA
      expression were unchanged. Increased expression of Factor VII was observed in
      phytoestrogen treated Hep89 cells but not in similarly treated HepG2s.
      Prothrombin gene expression was increased in equol and daidzein treated HepG2
      cells in the absence of the classical estrogen receptors. These data suggest that
      phytoestrogens can regulate the expression of coagulation and fibrinolytic genes
      in a human hepatocyte cell line; an effect which is augmented by ERalpha.

PMID- 23972792
TI  - Anti adipogenic activity of Aegle marmelos Correa.
AB  - In continuation of evaluating the anti-obesity effect of Aegle marmelos, we have
      screened the n-hexane, dichloro methane (DCM), ethyl acetate (EtOAc) and methanol
      (MeOH) extracts of the leaves at the concentration of 25, 50, 75 and 100 MUg/ml
      for adipogenesis inhibition in the adipocytes. Nile red staining with the help of
      fluorometry was used as indicator of the antiobesity activity. The most active
      DCM extract showed the 33.98+/-3.55% lipid content at 100MUg/ml and was selected
      for the further isolation. 14 compounds were isolated from DCM extract of A.
      marmelos leaves. The compounds were screened for the adipogenesis inhibition at
      50 and 100 MUM concentrations. Out of the 14 compounds, halfordinol, ethyl ether
      aegeline and esculetin were showing 10.04+/-0.52, 16.29+/-0.85 and 25.09+/-1.31%
      lipid content respectively at 100 MUM. We hereby report the adipogenesis
      inhibition by A. marmelos as one of the pathway for its antiobesity effect.

PMID- 23972794
TI  - Strengthening midwifery in Brazil: education, regulation and professional
      association of midwives.
AB  - This article describes Brazilian midwives' struggle to establish their
      professional field in the arena of maternal and child health in Brazil. Despite
      the obstacles, midwives continue trying to claim their social space, seeking to
      maintain and strengthen the profession, and legislative aspects of practice and
      regulation of their profession. They seek space in the job market, support from
      entities of civil society, representatives of judicial and political power, and
      from the movements organised for improvement and change in the birth care model
      in Brazil. 

PMID- 23972793
TI  - Attenuation of nucleoside and anti-cancer nucleoside analog drug uptake in
      prostate cancer cells by Cimicifuga racemosa extract BNO-1055.
AB  - This study aimed to investigate the mechanisms underlying the anti-proliferative
      effects of the ethanolic Cimicifuga racemosa extract BNO-1055 on prostate cells
      and evaluate its therapeutic potential. BNO-1055 dose-dependently attenuated
      cellular uptake and incorporation of thymidine and BrdU and significantly
      inhibited cell growth after long-time exposure. Similar results were obtained
      using saponin-enriched sub-fractions of BNO-1055. These inhibitory effects of BNO
      1055 could be mimicked using pharmacological inhibitors and isoform-specific
      siRNAs targeting the equilibrative nucleoside transporters ENT1 and ENT2.
      Moreover, BNO-1055 attenuated the uptake of clinically relevant nucleoside
      analogs, e.g. the anti-cancer drugs gemcitabine and fludarabine. Consistent with
      inhibition of the salvage nucleoside uptake pathway BNO-1055 potentiated the
      cytotoxicity of the de novo nucleotide synthesis inhibitor 5-FU without
      significantly altering its uptake. Collectively, these data show for the first
      time that the anti-proliferative effects of BNO-1055 result from hindered
      nucleoside uptake due to impaired ENT activity and demonstrate the potential
      therapeutic use of BNO-1055 for modulation of nucleoside transport. 

PMID- 23972795
TI  - Australian midwives' experience of delivering a counselling intervention for
      women reporting a traumatic birth.
AB  - OBJECTIVE: this paper describes midwives' experiences of learning new counselling
      skills and delivering a counselling intervention entitled 'Promoting Resilience
      on Mothers Emotions' (PRIME). DESIGN: a descriptive exploratory approach was
      used. Data collected included semi-structured interviews (n=42), midwife diary
      entries (18 pages) and web based postings (169 pages). Data were analysed using
      manual thematic method. SETTING: the intervention study was conducted in two
      tertiary maternity hospitals in the Australian states of Queensland (QLD) and
      Western Australia (WA) during a 17 month period, from August 2008 to December
      2009. PARTICIPANTS: midwives were employed as research assistants and trained to
      deliver a counselling intervention to women reporting a traumatic birth
      experience. Eighteen of a possible 20 Australian midwives participated in this
      study. INTERVENTION: PRIME is a midwife-led counselling intervention based on
      cognitive-behavioural principles and designed to ameliorate trauma symptoms. It
      is offered face-to-face within 72 hours of childbirth and by phone around six
      weeks post partum. FINDINGS: participating midwives felt confronted by the level
      of emotional distress some women suffered as a consequence of their birth
      experience. Four major themes were extracted: The challenges of learning to
      change; Working with women in a different way; Making a difference to women and
      me; and A challenge not about to be overcome. KEY CONCLUSIONS AND IMPLICATIONS
      FOR PRACTICE: the advanced counselling skills the midwives acquired improved
      their confidence to care for women distressed by their birthing experience and to
      personally manage stressful situations they encountered in practice.

PMID- 23972796
TI  - Lung cancer: a global scourge.

PMID- 23972797
TI  - Health-care workers with HIV: free to work again.

PMID- 23972798
TI  - Improving inpatient mental health care in the UK.

PMID- 23972799
TI  - Recording of smoking history in death notification.

PMID- 23972801
TI  - Rafael Rosell: leading the long march against lung cancer.

PMID- 23972802
TI  - Improving health in humanitarian crises: from reactive to proactive.

PMID- 23972803
TI  - Response to Syria's health crisis.

PMID- 23972804
TI  - Health after 2015: a human right?

PMID- 23972805
TI  - Worsening plight of Palestinian refugees in Syria.

PMID- 23972806
TI  - Trials of participation to improve maternal and newborn health.

PMID- 23972807
TI  - Trials of participation to improve maternal and newborn health - Authors' reply.

PMID- 23972808
TI  - Tobacco control has always challenged tobacco interests - Author's reply.

PMID- 23972809
TI  - Tobacco control has always challenged tobacco interests.

PMID- 23972810
TI  - Renaming schizophrenia in South Korea.

PMID- 23972811
TI  - Salt: friend or foe?

PMID- 23972812
TI  - Investment in cancer studies in countries of low and middle income.

PMID- 23972813
TI  - Differences among the coloured, white, black, and other South African populations
      in smoking-attributed mortality at ages 35-74 years: a case-control study of
      481,640 deaths.
AB  - BACKGROUND: The full eventual effects of current smoking patterns cannot yet be
      seen in Africa. In South Africa, however, men and women in the coloured (mixed
      black and white ancestry) population have smoked for many decades. We assess
      mortality from smoking in the coloured, white, and black (African) population
      groups. METHODS: In this case-control study, 481,640 South African notifications
      of death at ages 35-74 years between 1999 and 2007 yielded information about age,
      sex, population group, education, smoking 5 years ago (yes or no), and underlying
      disease. Cases were deaths from diseases expected to be affected by smoking;
      controls were deaths from selected other diseases, excluding only HIV, cirrhosis,
      unknown causes, external causes, and mental disorders. Disease-specific case
      control comparisons yielded smoking-associated relative risks (RRs; diluted by
      combining some ex-smokers with the never-smokers). These RRs, when combined with
      national mortality rates, yielded smoking-attributed mortality rates. Summation
      yielded RRs and smoking-attributed numbers for overall mortality. FINDINGS: In
      the coloured population, smoking prevalence was high in both sexes and smokers
      had about 50% higher overall mortality than did otherwise similar non-smokers or
      ex-smokers (men, RR 1.55, 95% CI 1.43-1.67; women, 1.49, 1.38-1.60). RRs were
      similar in the white population (men, 1.37, 1.29-1.46; women, 1.51, 1.40-1.62),
      but lower among Africans (men, 1.17, 1.15-1.19; women, 1.16, 1.13-1.20). If these
      associations are largely causal, smoking-attributed proportions for overall male
      deaths at ages 35-74 years were 27% (5608/20,767) in the coloured, 14%
      (3913/28,951) in the white, and 8% (20,398/264,011) in the African population.
      For female deaths, these proportions were 17% (2728/15,593) in the coloured, 12%
      (2084/17,899) in the white, and 2% (4038/205,623) in the African population.
      Because national mortality rates were also substantially higher in the coloured
      than in the white population, the hazards from smoking in the coloured population
      were more than double those in the white population. INTERPRETATION: The highest
      smoking-attributed mortality rates were in the coloured population and the lowest
      were in Africans. The substantial hazards already seen among coloured South
      Africans suggest growing hazards in all populations in Africa where young adults
      now smoke. FUNDING: South African Medical Research Council, UK Medical Research
      Council, Cancer Research UK, British Heart Foundation, New South Wales Cancer
      Council.

PMID- 23972814
TI  - Management of non-small-cell lung cancer: recent developments.
AB  - Non-small-cell lung cancer is one of the leading causes of deaths from cancer
      worldwide. Therefore, improvements in diagnostics and treatments are urgently
      needed. In this review, we will discuss the evolution of lung cancer staging
      towards more non-invasive, endoscopy-based, and image-based methods, and the
      development of stage-adapted treatment. A special focus will be placed on the
      role of novel surgical approaches and modern radiotherapy strategies for early
      stages of disease, the effect of multimodal treatment in locally advanced
      disease, and ongoing developments in the treatment of patients with metastatic
      disease. In particular, we will include an emphasis on targeted therapies, which
      are based on the assumption that a treatable driver mutation or gene
      rearrangement is present within the tumour. Finally, the position of lung cancer
      treatment on the pathway to personalised therapy will be discussed. 

PMID- 23972815
TI  - Genetics and biomarkers in personalisation of lung cancer treatment.
AB  - Non-small-cell lung cancer is often diagnosed at the metastatic stage, with
      median survival of just 1 year. The identification of driver mutations in the
      epidermal growth factor receptor (EGFR) as the primary oncogenic event in a
      subset of lung adenocarcinomas led to a model of targeted treatment and genetic
      profiling of the disease. EGFR tyrosine kinase inhibitors confer remission in 60%
      of patients, but responses are short-lived. The pre-existing EGFR Thr790Met
      mutation could be a subclonal driver responsible for these transient responses.
      Overexpression of AXL and reduced MED12 function are hallmarks of resistance to
      tyrosine kinase inhibitors in EGFR-mutant non-small-cell lung cancer. Crosstalk
      between signalling pathways is another mechanism of resistance; therefore,
      identification of the molecular components involved could lead to the development
      of combination therapies cotargeting these molecules instead of EGFR tyrosine
      kinase inhibitor monotherapy. Additionally, novel biomarkers could be identified
      through deep sequencing analysis of serial rebiopsies before and during
      treatment. 

PMID- 23972816
TI  - Prospects for population screening and diagnosis of lung cancer.
AB  - Deaths from lung cancer exceed those from any other type of malignancy, with 1.5
      million deaths in 2010. Prevention and smoking cessation are still the main
      methods to reduce the death toll. The US National Lung Screening Trial, which
      compared CT screening with chest radiograph, yielded a mortality advantage of 20%
      to participants in the CT group. International debate is ongoing about whether
      sufficient evidence exists to implement CT screening programmes. When questions
      about effectiveness and cost-effectiveness have been answered, which will await
      publication of the largest European trial, NELSON, and pooled analysis of
      European CT screening trials, we discuss the main topics that will need
      consideration. These unresolved issues are risk prediction models to identify
      patients for CT screening; radiological protocols that use volumetric analysis
      for indeterminate nodules; options for surgical resection of CT-identified
      nodules; screening interval; and duration of screening. We suggest that a
      demonstration project of biennial screening over a 4-year period should be
      undertaken. 

PMID- 23972817
TI  - Intestinal failure after bariatric surgery.

PMID- 23972818
TI  - Attitudes and expectations of patients with neuromuscular diseases about their
      participation in a clinical trial.
AB  - AIM: This study aimed to gain a better understanding of the psychological impact
      of participating in a clinical trial for patients with Pompe disease (Acid
      Maltase Deficiency). Attitudes and expectations of adult patients with
      neuromuscular diseases regarding medical trials are as yet unreported. In order
      to learn about the psychological consequences of participating in a clinical
      trial, we conducted a prospective assessment of patients with late-onset Pompe
      Disease, a rare genetic condition, for which no treatment had been available
      before. This psychological study was carried out as an ancillary study to the
      randomized double-blind placebo-controlled trial described elsewhere (van der
      Ploeg et al., 2010). SUBJECTS AND METHODS: We assessed patients (n=8) at
      inclusion, and at 12 and 18 months for six psychological dimensions: depression
      (Beck Depression Inventory, BDI), hopelessness (Beck Hopelessness Scale, BHS),
      anxiety (STAI A-B), quality of life (Whoqol-26), social adjustment (S.A.S-self
      report) and locus of control (IPC Levenson). We produced a self-administered
      questionnaire in order to assess the attitudes, motivations and expectations of
      patients during the trial. RESULTS: At 12 months, mean social adjustment (SAS-SR,
      P=0.02) had improved, and at 18 months mean depression score had improved as well
      (BDI, P=0.03). The quality of life of patients (Whoqol-26) remained unchanged.
      Throughout the study, patients were more likely to have an internal locus of
      control than an external one (IPC Levenson). The self-administered questionnaire
      showed that patients' expectations were disproportionate compared to the medical
      information they had received starting the trial. For all patients, the first
      motivation for being enrolled in a clinical trial was "to help research", for
      half of them the motivation was to "improve their health". Whether patients
      believed to be part of one group or another (placebo or treatment) depended on
      their subjective perception of improvement during the trial. CONCLUSION: Given
      the small sample size, the conclusions of this study are preliminary. However,
      findings do suggest that there is a positive psychological impact of
      participating in a treatment trial. Moreover, the patients' reactions upon
      unblinding have led us to recommend that patients be asked whether they would
      like their group assignation disclosed to them or not.

PMID- 23972819
TI  - The use of prothrombin complex concentrates in two patients with non-pulsatile
      left ventricular assist devices.

PMID- 23972820
TI  - Dynamic anterior mediastinal mass physiology after thoracotomy and dissection for
      left upper lobectomy.

PMID- 23972821
TI  - Risk of symptom recurrence with medication discontinuation in first-episode
      psychosis: a systematic review.
AB  - The large majority of individuals with a first episode of schizophrenia will
      experience a remission of symptoms within their first year of treatment. It is
      not clear how long treatment with antipsychotic medications should be continued
      in this situation. The possibility that a percentage of patients may not require
      ongoing treatment and may be unnecessarily exposed to the long-term risks of
      antipsychotic medications has led to the development of a number of studies to
      address this question. We carried out a systematic review to determine the risk
      of experiencing a recurrence of psychotic symptoms in individuals who have
      discontinued antipsychotic medications after achieving symptomatic remission from
      a first episode of non-affective psychosis (FEP). Six studies were identified
      that met our criteria and these reported a weighted mean one-year recurrence rate
      of 77% following discontinuation of antipsychotic medication. By two years, the
      risk of recurrence had increased to over 90%. By comparison, we estimated the one
      year recurrence rate for patients who continued antipsychotic medication to be
      3%. These findings suggest that in the absence of uncertainty about the diagnosis
      or concerns about the contribution of medication side effects to problems with
      health or functioning, a trial off of antipsychotic medications is associated
      with a very high risk of symptom recurrence and should thus not be recommended. 

PMID- 23972822
TI  - [Hepatitis C virus genotype 5 in Mexico: a case report with successful treatment
      and a literature review].
AB  - Hepatitis C virus (HCV) genotype 5 is extremely rare and there is very little
      reported on its management in the medical literature. We present herein the case
      of a patient with HCV genotype 5 that presumably acquired the disease through a
      blood transfusion during infancy. Sustained virologic response was achieved after
      24 weeks of treatment. According to the available information on HCV genotype 5
      treatment, it has a similar response to that of HCV genotype 1. Our patient
      presented with various favorable outcome factors. There is much less reported on
      the treatment of HCV genotype 5 than there is regarding HCV genotypes 1, 2, 3,
      and 4. This is mainly due to the low prevalence of genotype 5 in the Mexican
      environment. 

PMID- 23972823
TI  - The growth factor progranulin attenuates neuronal injury induced by cerebral
      ischemia-reperfusion through the suppression of neutrophil recruitment.
AB  - BACKGROUND: To improve the clinical outcome of patients who suffered ischemic
      stroke, cerebral ischemia-reperfusion (I/R) injury is one of the major concerns
      that should be conquered. Inflammatory reactions are considered a major
      contributor to brain injury following cerebral ischemia, and I/R exacerbates
      these reactions. The aim of this study was to investigate the possible
      ameliorative effects of progranulin (PGRN) against I/R injury in mice. METHODS:
      In vivo I/R was induced in four-week-old male ddY mice by 2 h of MCAO (middle
      cerebral artery occlusion) followed by 22 h of reperfusion. We evaluate
      expression of PGRN in I/R brain, efficacy of recombinant-PGRN (r-PGRN) treatment
      and its therapeutic time-window on I/R injury. Two hours after MCAO, 1.0 ng of r
      PRGN or PBS was administered via intracerebroventricular. We assess neutrophil
      infiltration, expression of tumor necrosis factor (TNF)-alpha, matrix
      metalloproteinase-9 (MMP-9) and phosphorylation of nuclear factor-kappaB (NF
      kappaB) by immunofluorescense staining and Western blotting. We also investigate
      neutrophil chemotaxis and intercellular adhesion molecule-1 (ICAM-1) expression
      in vitro inflammation models using isolated neutrophils and endothelial cells.
      RESULTS: We found that expression of PGRN was decreased in the I/R mouse brain. r
      PGRN treatment at 2 h after MCAO resulted in a reduction in the infarct volume
      and decreased brain swelling; this led to an improvement in neurological scores
      and to a reduction of mortality rate at 24 h and 7 d after MCAO, respectively.
      Immunohistochemistry, Western blotting, and gelatin zymography also confirmed
      that r-PGRN treatment suppressed neutrophil recruitment into the I/R brain, and
      this led to a reduction of NF-kappaB and MMP-9 activation. In the in vitro
      inflammation models, PGRN suppressed both the neutrophil chemotaxis and ICAM-1
      expression caused by TNF-alpha in endothelial cells. CONCLUSIONS: PGRN exerted
      ameliorative effects against I/R-induced inflammation, and these effects may be
      due to the inhibition of neutrophil recruitment into the I/R brain.

PMID- 23972824
TI  - Comparison of pathogens and antibiotic resistance of burn patients in the burn
      ICU or in the common burn ward.
AB  - BACKGROUND: This study aims to compare pathogens and their antibiotic resistances
      of burn patients from burn intensive care unit (ICU) or common burn ward. Of 2395
      clinical samples from 63 patients in burn ICU, pathogens were detected in 1621
      samples, in which 1203 strains (74.2%) were Gram negative bacteria, 248 strains
      (15.3%) were Gram positive bacteria, 170 strains (10.5%) were fungi. Top-4
      microorganisms isolated from patients in burn ICU were Bauman's Acinetobacter
      (557, 34.4%), Pseudomonas aeruginosa (287.17.7%), Staphylococcus aureus (199,
      12.3%) and Klebsiella pneumoniae (171, 10.5%). Of 512 clinical samples from 235
      patients in common burn units, pathogens were detected in 373 samples, in which
      189 (50.6%) strains were Gram negative bacteria, 150 strains (40.2%) were Gram
      positive bacteria, 34 strains (9.2%) were fungi. Top-4 microorganisms isolated
      from patients in common burn units were S. aureus (103, 27.6%), P. aeruginosa
      (46, 12.3%), K. pneumoniae (38, 10.2%) and Escherichia coli (32, 8.6%).
      Antibiotic resistance rates of pathogens isolated from clinical samples of burn
      patients from ICU was significantly higher than those from common units.
      CONCLUSIONS: Pathogens and their antibiotic resistances are significantly
      different between burn ICU and common burn units. This finding has great
      implication for infection control in burn patients.

PMID- 23972825
TI  - Global implementation of WHO's multimodal strategy for improvement of hand
      hygiene: a quasi-experimental study.
AB  - BACKGROUND: Health-care-associated infections are a major threat to patient
      safety worldwide. Transmission is mainly via the hands of health-care workers,
      but compliance with recommendations is usually low and effective improvement
      strategies are needed. We assessed the effect of WHO's strategy for improvement
      of hand hygiene in five countries. METHODS: We did a quasi-experimental study
      between December, 2006, and December, 2008, at six pilot sites (55 departments in
      43 hospitals) in Costa Rica, Italy, Mali, Pakistan, and Saudi Arabia. A step-wise
      approach in four 3-6 month phases was used to implement WHO's strategy and we
      assessed the hand-hygiene compliance of health-care workers and their knowledge,
      by questionnaire, of microbial transmission and hand-hygiene principles. We
      expressed compliance as the proportion of predefined opportunities met by hand
      hygiene actions (ie, handwashing or hand rubbing). We assessed long-term
      sustainability of core strategy activities in April, 2010. FINDINGS: We noted
      21,884 hand-hygiene opportunities during 1423 sessions before the intervention
      and 23,746 opportunities during 1784 sessions after. Overall compliance increased
      from 51.0% before the intervention (95% CI 45.1-56.9) to 67.2% after (61.8-72.2).
      Compliance was independently associated with gross national income per head, with
      a greater effect of the intervention in low-income and middle-income countries
      (odds ratio [OR] 4.67, 95% CI 3.16-6.89; p<0.0001) than in high-income countries
      (2.19, 2.03-2.37; p<0.0001). Implementation had a major effect on compliance of
      health-care workers across all sites after adjustment for main confounders (OR
      2.15, 1.99-2.32). Health-care-workers' knowledge improved at all sites with an
      increase in the average score from 18.7 (95% CI 17.8-19.7) to 24.7 (23.7-25.6)
      after educational sessions. 2 years after the intervention, all sites reported
      ongoing hand-hygiene activities with sustained or further improvement, including
      national scale-up. INTERPRETATION: Implementation of WHO's hand-hygiene strategy
      is feasible and sustainable across a range of settings in different countries and
      leads to significant compliance and knowledge improvement in health-care workers,
      supporting recommendation for use worldwide. FUNDING: WHO, University of Geneva
      Hospitals, the Swiss National Science Foundation, Swiss Society of Public Health
      Administration and Hospital Pharmacists.

PMID- 23972826
TI  - International implementation of WHO's hand hygiene strategy.

PMID- 23972827
TI  - Low-frequency otoacoustic emissions in schoolchildren measured by two commercial
      devices.
AB  - OBJECTIVE: Click evoked otoacoustic emissions in children are known to be good
      indicators of hearing function when used in the frequency range 1.5-4 kHz. Using
      two commercial devices, the present study investigates the usefulness of
      responses in the lower frequency range of 0.5-1 kHz evoked by 0.5 kHz tone
      bursts. METHODS: Otoacoustic emissions (OAEs) were recorded from the ears of 37
      schoolchildren (age 12-13 years). OAE measurements were then made using two
      devices: the ILO 292 (Otodynamics) and the HearId (Mimosa Acoustics). Each device
      was used for two measurements: first with a standard click stimulus at 80 dB pSPL
      (CEOAEs) and a second using a 0.5 kHz tone burst at 80 dB pSPL (TBOAEs). Pure
      tone audiometry and tympanometry were also conducted. Half-octave-band values of
      OAE signal to noise ratios (SNRs) and response levels were used to assess
      statistical differences. RESULTS: Both devices provided similar SNR results for
      click and tone burst stimuli, although the ILO device generated slightly higher
      response levels for clicks. For the 0.5 kHz tone bursts, both devices evoked very
      weak responses at 0.5 kHz and the peak response occurred at 0.7-1 kHz. Generally,
      CEOAE SNRs were about 10 dB in the 1-4 kHz range, while SNRs for 0.5 kHz TBOAEs
      were about 10 dB at 0.7-1 kHz. CONCLUSIONS: 0.5 kHz TBOAEs could be measured in
      children as effectively as CEOAEs. They can provide additional information about
      the 0.7-1 kHz frequency range, a range over which CEOAEs do not usually contain
      responses above the noise floor. The main difficulty was that the maxima of the
      0.5 kHz TBOAEs occurred at frequencies of 0.7-1 kHz, probably because of spectral
      splatter from the short tone burst stimulus and from rapidly falling responses of
      the cochlea and the recording system at low frequencies.

PMID- 23972828
TI  - [Head and neck adaptive radiotherapy].
AB  - Onboard volumetric imaging systems can provide accurate data of the patient's
      anatomy during a course of head and neck radiotherapy making it possible to
      assess the actual delivered dose and to evaluate the dosimetric impact of complex
      daily positioning variations and gradual anatomic changes such as geometric
      variations of tumors and normal tissues or shrinkage of external contours.
      Adaptive radiotherapy is defined as the correction of a patient's treatment
      planning to adapt for individual variations observed during treatment. Strategies
      are developed to selectively identify patients that require replanning because of
      an intolerable dosimetric drift. Automated tools are designed to limit time
      consumption. Deformable image registration algorithms are the cornerstones of
      these strategies, but a better understanding of their limits of validity is
      required before adaptive radiotherapy can be safely introduced to daily practice.
      Moreover, strict evaluation of the clinical benefits is yet to be proven. 

PMID- 23972829
TI  - [General anesthesia in pediatric radiotherapy].
AB  - BACKGROUND: The majority of children under 3 years require anesthesia for
      radiotherapy. METHODS: This work reports the experience of Paul-Strauss Center
      over a 4-year period on 15 children and covering 386 general anesthesia. RESULTS
      AND CONCLUSION: The rate of anesthesia-related complications was low (0.5%)
      subject to the experience of the anesthesiologists and follow-up recommendations.

PMID- 23972830
TI  - Fluctuation imaging spiced up with a piece of PIE.

PMID- 23972831
TI  - Milestoning simulation reveals mechanism of helix-breaking.

PMID- 23972832
TI  - Slower Piezo1 inactivation in dehydrated hereditary stomatocytosis (xerocytosis).

PMID- 23972833
TI  - Is it zippered? Does it flare? That darn complexin clamping SNARE.

PMID- 23972834
TI  - Fast and furious: the mass and motion of stem cells.

PMID- 23972835
TI  - New insights into cochlear amplification.

PMID- 23972836
TI  - Optical-resolution photoacoustic microscopy: auscultation of biological systems
      at the cellular level.
AB  - Photoacoustic microscopy (PAM) offers unprecedented sensitivity to optical
      absorption and opens a new window to study biological systems at multiple length-
      and timescales. In particular, optical-resolution PAM (OR-PAM) has pushed the
      technical envelope to submicron length scales and millisecond timescales. Here,
      we review the state of the art of OR-PAM in biophysical research. With properly
      chosen optical wavelengths, OR-PAM can spectrally differentiate a variety of
      endogenous and exogenous chromophores, unveiling the anatomical, functional,
      metabolic, and molecular information of biological systems. Newly uncovered
      contrast mechanisms of linear dichroism and Forster resonance energy transfer
      further distinguish OR-PAM. Integrating multiple contrasts and advanced scanning
      mechanisms has capacitated OR-PAM to comprehensively interrogate biological
      systems at the cellular level in real time. Two future directions are discussed,
      where OR-PAM holds the potential to translate basic biophysical research into
      clinical healthcare. 

PMID- 23972837
TI  - Pulsed interleaved excitation fluctuation imaging.
AB  - Fluorescence fluctuation imaging is a powerful means to investigate dynamics,
      interactions, and stoichiometry of proteins inside living cells. Pulsed
      interleaved excitation (PIE) is the method of nanosecond alternating excitation
      with time-resolved detection and allows accurate, independent, and quasi
      simultaneous determination of fluorescence intensities and lifetimes of different
      fluorophores. In this work, we combine pulsed interleaved excitation with
      fluctuation imaging methods (PIE-FI) such as raster image correlation
      spectroscopy (RICS) or number and brightness analysis (N&B). More specifically,
      we show that quantitative measurements of diffusion and molecular brightness of
      Venus fluorescent protein (FP) can be performed in solution with PIE-RICS and
      compare PIE-RICS with single-point PIE-FCS measurements. We discuss the
      advantages of cross-talk free dual-color PIE-RICS and illustrate its proficiency
      by quantitatively comparing two commonly used FP pairs for dual-color microscopy,
      eGFP/mCherry and mVenus/mCherry. For N&B analysis, we implement dead-time
      correction to the PIE-FI data analysis to allow accurate molecular brightness
      determination with PIE-NB. We then use PIE-NB to investigate the effect of eGFP
      tandem oligomerization on the intracellular maturation efficiency of the
      fluorophore. Finally, we explore the possibilities of using the available
      fluorescence lifetime information in PIE-FI experiments. We perform lifetime
      based weighting of confocal images, allowing us to quantitatively determine
      molecular concentrations from 100 nM down to <30 pM with PIE-raster lifetime
      image correlation spectroscopy (RLICS). We use the fluorescence lifetime
      information to perform a robust dual-color lifetime-based FRET analysis of tandem
      fluorescent protein dimers. Lastly, we investigate the use of dual-color RLICS to
      resolve codiffusing FRET species from non-FRET species in cells. The enhanced
      capabilities and quantitative results provided by PIE-FI make it a powerful
      method that is broadly applicable to a large number of interesting biophysical
      studies. 

PMID- 23972838
TI  - Optoporation and genetic manipulation of cells using femtosecond laser pulses.
AB  - Femtosecond laser optoporation is a powerful technique to introduce membrane
      impermeable molecules, such as DNA plasmids, into targeted cells in culture, yet
      only a narrow range of laser regimes have been explored. In addition, the
      dynamics of the laser-produced membrane pores and the effect of pore behavior on
      cell viability and transfection efficiency remain poorly elucidated. We studied
      optoporation in cultured cells using tightly focused femtosecond laser pulses in
      two irradiation regimes: millions of low-energy pulses and two higher-energy
      pulses. We quantified the pore radius and resealing time as a function of
      incident laser energy and determined cell viability and transfection efficiency
      for both irradiation regimes. These data showed that pore size was the governing
      factor in cell viability, independently of the laser irradiation regime. For
      viable cells, larger pores resealed more quickly than smaller pores, ruling out a
      passive resealing mechanism. Based on the pore size and resealing time, we
      predict that few DNA plasmids enter the cell via diffusion, suggesting an
      alternative mechanism for cell transfection. Indeed, we observed fluorescently
      labeled DNA plasmid adhering to the irradiated patch of the cell membrane,
      suggesting that plasmids may enter the cell by adhering to the membrane and then
      being translocated. 

PMID- 23972839
TI  - Yield strength of human erythrocyte membranes to impulsive stretching.
AB  - Deformability while remaining viable is an important mechanical property of
      cells. Red blood cells (RBCs) deform considerably while flowing through small
      capillaries. The RBC membrane can withstand a finite strain, beyond which it
      ruptures. The classical yield areal strain of 2-4% for RBCs is generally accepted
      for a quasi-static strain. It has been noted previously that this threshold
      strain may be much larger with shorter exposure duration. Here we employ an
      impulse-like forcing to quantify this yield strain of RBC membranes. In the
      experiments, RBCs are stretched within tens of microseconds by a strong shear
      flow generated from a laser-induced cavitation bubble. The deformation of the
      cells in the strongly confined geometry is captured with a high-speed camera and
      viability is successively monitored with fluorescence microscopy. We find that
      the probability of cell survival is strongly dependent on the maximum strain.
      Above a critical areal strain of ~40%, permanent membrane damage is observed for
      50% of the cells. Interestingly, many of the cells do not rupture immediately and
      exhibit ghosting, but slowly obtain a round shape before they burst. This
      observation is explained with structural membrane damage leading to subnanometer
      sized pores. The cells finally lyse from the colloidal osmotic pressure
      imbalance. 

PMID- 23972840
TI  - Human PIEZO1: removing inactivation.
AB  - PIEZO1 is an inactivating eukaryotic cation-selective mechanosensitive ion
      channel. Two sites have been located in the channel that when individually
      mutated lead to xerocytotic anemia by slowing inactivation. By introducing
      mutations at two sites, one associated with xerocytosis and the other artificial,
      we were able to remove inactivation. The double mutant (DhPIEZO1) has a
      substitution of arginine for methionine (M2225R) and lysine for arginine
      (R2456K). The loss of inactivation was accompanied by ~30-mmHg shift of the
      activation curve to lower pressures and slower rates of deactivation. The slope
      sensitivity of gating was the same for wild-type and mutants, indicating that the
      dimensional changes between the closed and open state are unaffected by the
      mutations. The unitary channel conductance was unchanged by mutations, so these
      sites are not associated with pore. DhPIEZO1 was reversibly inhibited by the
      peptide GsMTx4 that acted as a gating modifier. The channel kinetics were solved
      using complex stimulus waveforms and the data fit to a three-state loop in
      detailed balance. The reaction had two pressure-dependent rates, closed to open
      and inactivated to closed. Pressure sensitivity of the opening rate with no
      sensitivity of the closing rate means that the energy barrier between them is
      located near the open state. Mutant cycle analysis of inactivation showed that
      the two sites interacted strongly, even though they are postulated to be on
      opposite sides of the membrane. 

PMID- 23972841
TI  - The 5-HT3AB receptor shows an A3B2 stoichiometry at the plasma membrane.
AB  - The 5-HT3AB receptor is the best-characterized heteropentameric 5-HT3 receptor.
      Under conditions of heterologous expression, the 5-HT3AB receptor shows a single
      functionally resolvable population, suggesting the presence of a unique subunit
      stoichiometry; however, conflicting previous reports have suggested two different
      possible stoichiometries. Here we isolate plasma membrane sheets containing
      assembled receptors from individual HEK293T cells. We then determine the
      stoichiometry of 5-HT3AB receptors on the plasma membrane by fluorescence
      methods, employing meCFP- and meYFP-labeled A and B subunits. Over a wide range
      of cDNA transfection ratios, fluorescence intensity ratios are closest to values
      that correspond to a subunit ratio of A3B2. Forster resonance energy transfer
      (family FRET) efficiencies provide minor corrections (3-6%) to the subunit ratios
      and provide independent support for a predominantly A3B2 stoichiometry on the
      plasma membrane sheets. Twin FRET efficiencies support these data, also
      suggesting that the two B subunits are nonadjacent in most of the
      heteropentamers. The high-frequency variant HTR3B p.Y129S (c.386A>C, rs11767445),
      linked to psychiatric disease, also forms A3B2 receptors on the plasma membrane.
      The 5-HT3B Y129S, subunit incorporates in a slightly (11-14%) more efficient
      manner than the common variant. In general, most of the subunits reside within
      the cell. In contrast to the findings for the plasma membrane, the relative
      abundances and FRET characteristics of intracellular subunits depend strongly on
      the transfection ratio. The straightforward and unambiguous combination of plasma
      membrane-sheet isolation, fluorescence intensity ratios, and FRET is a generally
      promising procedure for determining stoichiometry of proteins on the plasma
      membrane.

PMID- 23972842
TI  - Embedding Abeta42 in heterogeneous membranes depends on cholesterol asymmetries.
AB  - Using a coarse-grained lipid and peptide model, we show that the free energy
      stabilization of amyloid-beta in heterogeneous lipid membranes is predicted to
      have a dependence on asymmetric distributions of cholesterol compositions across
      the membrane leaflets. We find that a highly asymmetric cholesterol distribution
      that is depleted on the exofacial leaflet but enhanced on the cytofacial leaflet
      of the model lipid membrane thermodynamically favors membrane retention of a
      fully embedded Abeta peptide. However, in the case of cholesterol redistribution
      that increases concentration of cholesterol on the exofacial layer, typical of
      aging or Alzheimer's disease, the free energy favors peptide extrusion of the
      highly reactive N-terminus into the extracellular space that may be vulnerable to
      aggregation, oligomerization, or deleterious oxidative reactivity. 

PMID- 23972843
TI  - Localization of cholesterol and fatty acid in a model lipid membrane: a neutron
      diffraction approach.
AB  - The intercellular lipid matrix of the skin's stratum corneum serves to protect
      the body against desiccation and simultaneously limits the passage of drugs and
      other xenobiotics into the body. The matrix is made up of ceramides, free fatty
      acids, and cholesterol, which are organized as two coexisting crystalline
      lamellar phases. In studies reported here, we sought to use the technique of
      neutron diffraction, together with the device of isotopic (H/D) substitution, to
      determine the molecular architecture of the lamellar phase having a repeat
      distance of 53.9 +/- 0.3 A. Using hydrogenous samples as well as samples
      incorporating perdeuterated (C24:0) fatty acids and selectively deuterated
      cholesterol, the diffraction data obtained were used to construct neutron
      scattering length density profiles. By this means, the locations within the unit
      cell were determined for the cholesterol and fatty acids. The cholesterol
      headgroup was found to lie slightly inward from the unit cell boundary and the
      tail of the molecule located 6.2 +/- 0.2 A from the unit cell center. The fatty
      acid headgroups were located at the unit cell boundary with their acyl chains
      straddling the unit cell center. Based on these results, a molecular model is
      proposed for the arrangement of the lipids within the unit cell. 

PMID- 23972844
TI  - Coexistence of probe conformations in lipid phases-a polarized fluorescence
      microspectroscopy study.
AB  - Several well-established fluorescence methods depend on environment-sensitive
      probes that report about molecular properties of their local environment. For
      reliable interpretation of experiments, careful characterization of probes'
      behavior is required. In this study, bleaching-corrected polarized fluorescence
      microspectroscopy with nanometer spectral peak position resolution was applied to
      characterize conformations of two alkyl chain-labeled 7-nitro-2-1,3-benzoxadiazol
      4-yl phospholipids in three model membranes, representing the three main lipid
      phases. The combination of polarized and spectral detection revealed two main
      probe conformations with their preferential fluorophore dipole orientations
      roughly parallel and perpendicular to membrane normal. Their peak positions were
      separated by 2-6 nm because of different local polarities and depended on lipid
      environment. The relative populations of conformations, estimated by a numerical
      model, indicated a specific sensitivity of the two probes to molecular packing
      with cholesterol. The coexistence of probe conformations could be further
      exploited to investigate membrane organization below microscopy spatial
      resolution, such as lipid rafts. With the addition of polarized excitation or
      detection to any environment-sensitive fluorescence imaging technique, the
      conformational analysis can be directly applied to explore local membrane
      complexity. 

PMID- 23972846
TI  - A mechanistic model of Ca regulation of thin filaments in cardiac muscle.
AB  - We present a model of Ca-regulated thin filaments in cardiac muscle where
      tropomyosin is treated as a continuous elastic chain confined in the closed
      position on the actin helix by electrostatic forces. The main distinction from
      previous works is that the intrinsic stress-free helical shape of the tropomyosin
      chain was taken into account explicitly. This results in the appearance of a new,
      to our knowledge, tension-like term in the energy functional and the equilibrium
      equation. The competitive binding of calcium and the mobile segment of troponin-I
      to troponin-C were described by a simple kinetic scheme. The values of
      dimensionless model parameters were estimated from published data. A stochastic
      Monte Carlo simulation of calcium curves has been performed and its results were
      compared to published data. The model explains the high cooperativity of calcium
      response of the regulated thin filaments even in the absence of myosin heads. The
      binding of myosin heads to actin increases the calcium sensitivity while not
      affecting its cooperativity significantly. When the presence of calcium
      insensitive troponin-C was simulated in the model, both calcium sensitivity and
      cooperativity decreased. All these features were previously observed
      experimentally. 

PMID- 23972845
TI  - A cross-bridge cycle with two tension-generating steps simulates skeletal muscle
      mechanics.
AB  - We examined whether cross-bridge cycle models with one or two tension-generating
      steps can account for the force-velocity relation of and tension response to
      length steps of frog skeletal muscle. Transition-state theory defined the strain
      dependence of the rate constants. The filament stiffness was non-Hookean. Models
      were refined against experimental data by simulated annealing and downhill
      simplex runs. Models with one tension-generating step were rejected, as they had
      a low efficiency and fitted the experimental data relatively poorly. The best
      model with two tension-generating steps (stroke distances 5.6 and 4.6 nm) and a
      cross-bridge stiffness of 1.7 pN/nm gave a good account of the experimental data.
      The two tensing steps allow an efficiency of up to 38% during shortening. In an
      isometric contraction, 54.7% of the attached heads were in a pre-tension
      generating state, 44.5% of the attached heads had undergone the first tension
      generating step, and only 0.8% had undergone both tension-generating steps; they
      bore 34%, 64%, and 2%, respectively, of the isometric tension. During slow
      shortening, the second tensing step made a greater contribution. During
      lengthening, up to 93% of the attached heads were in a pre-tension-generating
      state yet bore elevated tension by being dragged to high strains before
      detaching. 

PMID- 23972847
TI  - Coiled-coil response to mechanical force: global stability and local cracking.
AB  - Coiled coils are important structural motifs formed by two or more amphipathic
      alpha-helices that twist into a supercoil. These motifs are found in a wide range
      of proteins, including motor proteins and structural proteins, that are known to
      transmit mechanical loads. We analyze atomically detailed simulations of coiled
      coil cracking under load with Milestoning. Milestoning is an approach that
      captures the main features of the process in a network, quantifying kinetics and
      thermodynamics. A 112-residue segment of the beta-myosin S2 domain was subjected
      to constant-magnitude (0-200 pN) and constant-direction tensile forces in
      molecular dynamics simulations. Twenty 20 ns straightforward simulations at
      several load levels revealed that initial single-residue cracking events (Psi >
      90 degrees ) at loads <100 pN were accompanied by rapid refolding without either
      intra- or interhelix unfolding propagation. Only initial unfolding events at the
      highest load (200 pN) regularly propagated along and between helices. Analysis of
      hydrophobic interactions and of interhelix hydrogen bonds did not show
      significant variation as a function of load. Unfolding events were overwhelmingly
      located in the vicinity of E929, a charged residue in a hydrophobic position of
      the heptad repeat. Milestoning network analysis of E929 cracking determined that
      the mean first-passage time ranges from 20 ns (200 pN) to 80 ns (50 pN), which is
      ~20 times the mean first-passage time of an isolated helix with the same
      sequence.

PMID- 23972848
TI  - Accurate SAXS profile computation and its assessment by contrast variation
      experiments.
AB  - A major challenge in structural biology is to characterize structures of proteins
      and their assemblies in solution. At low resolution, such a characterization may
      be achieved by small angle x-ray scattering (SAXS). Because SAXS analyses often
      require comparing profiles calculated from many atomic models against those
      determined by experiment, rapid and accurate profile computation from molecular
      structures is needed. We developed fast open-source x-ray scattering (FoXS) for
      profile computation. To match the experimental profile within the experimental
      noise, FoXS explicitly computes all interatomic distances and implicitly models
      the first hydration layer of the molecule. For assessing the accuracy of the
      modeled hydration layer, we performed contrast variation experiments for glucose
      isomerase and lysozyme, and found that FoXS can accurately represent density
      changes of this layer. The hydration layer model was also compared with a SAXS
      profile calculated for the explicit water molecules in the high-resolution
      structures of glucose isomerase and lysozyme. We tested FoXS on eleven protein,
      one DNA, and two RNA structures, revealing superior accuracy and speed versus
      CRYSOL, AquaSAXS, the Zernike polynomials-based method, and Fast-SAXS-pro. In
      addition, we demonstrated a significant correlation of the SAXS score with the
      accuracy of a structural model. Moreover, FoXS utility for analyzing
      heterogeneous samples was demonstrated for intrinsically flexible XLF-XRCC4
      filaments and Ligase III-DNA complex. FoXS is extensively used as a standalone
      web server as a component of integrative structure determination by programs IMP,
      Chimera, and BILBOMD, as well as in other applications that require rapidly and
      accurately calculated SAXS profiles. 

PMID- 23972849
TI  - Altered backbone and side-chain interactions result in route heterogeneity during
      the folding of interleukin-1beta (IL-1beta).
AB  - Deletion of the beta-bulge trigger-loop results in both a switch in the preferred
      folding route, from the functional loop packing folding route to barrel closure,
      as well as conversion of the agonist activity of IL-1beta into antagonist
      activity. Conversely, circular permutations of IL-1beta conserve the functional
      folding route as well as the agonist activity. These two extremes in the folding
      functional interplay beg the question of whether mutations in IL-1beta would
      result in changes in the populations of heterogeneous folding routes and the
      signaling activity. A series of topologically equivalent water-mediated beta
      strand bridging interactions within the pseudosymmetric beta-trefoil fold of IL
      1beta highlight the backbone water interactions that stabilize the secondary and
      tertiary structure of the protein. Additionally, conserved aromatic residues
      lining the central cavity appear to be essential for both stability and folding.
      Here, we probe these protein backbone-water molecule and side chain-side chain
      interactions and the role they play in the folding mechanism of this
      geometrically stressed molecule. We used folding simulations with structure-based
      models, as well as a series of folding kinetic experiments to examine the effects
      of the F42W core mutation on the folding landscape of IL-1beta. This mutation
      alters water-mediated backbone interactions essential for maintaining the trefoil
      fold. Our results clearly indicate that this perturbation in the primary
      structure alters a structural water interaction and consequently modulates the
      population of folding routes accessed during folding and signaling activity. 

PMID- 23972850
TI  - Ion competition in condensed DNA arrays in the attractive regime.
AB  - Physical origin of DNA condensation by multivalent cations remains unsettled.
      Here, we report quantitative studies of how one DNA-condensing ion (Cobalt(3+)
      Hexammine, or Co(3+)Hex) and one nonDNA-condensing ion (Mg(2+)) compete within
      the interstitial space in spontaneously condensed DNA arrays. As the ion
      concentrations in the bath solution are systematically varied, the ion contents
      and DNA-DNA spacings of the DNA arrays are determined by atomic emission
      spectroscopy and x-ray diffraction, respectively. To gain quantitative insights,
      we first compare the experimentally determined ion contents with predictions from
      exact numerical calculations based on nonlinear Poisson-Boltzmann equations. Such
      calculations are shown to significantly underestimate the number of Co(3+)Hex
      ions, consistent with the deficiencies of nonlinear Poisson-Boltzmann approaches
      in describing multivalent cations. Upon increasing the concentration of Mg(2+),
      the Co(3+)Hex-condensed DNA array expands and eventually redissolves as a result
      of ion competition weakening DNA-DNA attraction. Although the DNA-DNA spacing
      depends on both Mg(2+) and Co(3+)Hex concentrations in the bath solution, it is
      observed that the spacing is largely determined by a single parameter of the DNA
      array, the fraction of DNA charges neutralized by Co(3+)Hex. It is also observed
      that only ~20% DNA charge neutralization by Co(3+)Hex is necessary for
      spontaneous DNA condensation. We then show that the bath ion conditions can be
      reduced to one variable with a simplistic ion binding model, which is able to
      describe the variations of both ion contents and DNA-DNA spacings reasonably
      well. Finally, we discuss the implications on the nature of interstitial ions and
      cation-mediated DNA-DNA interactions. 

PMID- 23972851
TI  - Characterizing a histidine switch controlling pH-dependent conformational changes
      of the influenza virus hemagglutinin.
AB  - During the fusion of the influenza virus to the host cell, bending of the HA2
      chain of hemagglutinin into a hairpin-shaped structure in a pH-dependent manner
      facilitates the fusion of the viral envelope and the endosomal membrane. To
      characterize the structural and dynamical responses of the hinge region of HA2 to
      pH changes and examine the role of a conserved histidine in this region (the
      hinge histidine), we have performed an extensive set of molecular dynamics (MD)
      simulations of 26-residue peptides encompassing the hinge regions of several
      hemagglutinin subtypes under both neutral and low pH conditions, modeled by the
      change of the protonation state of the hinge histidine. More than 70 sets of MD
      simulations (collectively amounting to 25.1 MUs) were performed in both implicit
      and explicit solvents to study the effect of histidine protonation on structural
      dynamics of the hinge region. In both explicit and implicit solvent simulations,
      hinge bending was consistently observed upon the protonation of the histidine in
      all the simulations starting with an initial straight helical conformation,
      whereas the systems with a neutral histidine retained their primarily straight
      conformation throughout the simulations. Conversely, the MD simulations starting
      from an initially bent conformation resulted in the formation of a straight
      helical structure upon the neutralization of the hinge histidine, whereas the
      bent structure was maintained when the hinge histidine remained protonated.
      Finally, mutation of the hinge histidine to alanine abolishes the bending
      response of the peptide altogether. A molecular mechanism based on the
      interaction of the hinge histidine with neighboring acidic residues is proposed
      to be responsible for its role in controlling the conformation of the hinge. We
      propose that this might present a common mechanism for pH-controlled structural
      changes in helical structures when histidines act as the pH sensor. 

PMID- 23972852
TI  - The arginine-rich RNA-binding motif of HIV-1 Rev is intrinsically disordered and
      folds upon RRE binding.
AB  - Arginine-rich motifs (ARMs) capable of binding diverse RNA structures play
      critical roles in transcription, translation, RNA trafficking, and RNA packaging.
      The regulatory HIV-1 protein Rev is essential for viral replication and belongs
      to the ARM family of RNA-binding proteins. During the early stages of the HIV-1
      life cycle, incompletely spliced and full-length viral mRNAs are very
      inefficiently recognized by the splicing machinery of the host cell and are
      subject to degradation in the cell nucleus. These transcripts harbor the Rev
      Response Element (RRE), which orchestrates the interaction with the Rev ARM and
      the successive Rev-dependent mRNA export pathway. Based on established criteria
      for predicting intrinsic disorder, such as hydropathy, combined with significant
      net charge, the very basic primary sequences of ARMs are expected to adopt coil
      like structures. Thus, we initiated this study to investigate the conformational
      changes of the Rev ARM associated with RNA binding. We used multidimensional NMR
      and circular dichroism spectroscopy to monitor the observed structural
      transitions, and described the conformational landscapes using statistical
      ensemble and molecular-dynamics simulations. The combined spectroscopic and
      simulated results imply that the Rev ARM is intrinsically disordered not only as
      an isolated peptide but also when it is embedded into an oligomerization
      deficient Rev mutant. RRE recognition triggers a crucial coil-to-helix transition
      employing an induced-fit mechanism. 

PMID- 23972853
TI  - The specificity of controlled protein disorder in the photoprotection of plants.
AB  - Light-harvesting pigment-protein complexes of photosystem II of plants have a
      dual function: they efficiently use absorbed energy for photosynthesis at
      limiting sunlight intensity and dissipate the excess energy at saturating
      intensity for photoprotection. Recent single-molecule spectroscopy studies on the
      trimeric LHCII complex showed that environmental control of the intrinsic protein
      disorder could in principle explain the switch between their light-harvesting and
      photoprotective conformations in vivo. However, the validity of this proposal
      depends strongly on the specificity of the protein dynamics. Here, a similar
      study has been performed on the minor monomeric antenna complexes of photosystem
      II (CP29, CP26, and CP24). Despite their high structural homology, similar
      pigment content and organization compared to LHCII trimers, the environmental
      response of these proteins was found to be rather distinct. A much larger
      proportion of the minor antenna complexes were present in permanently weakly
      fluorescent states under most conditions used; however, unlike LHCII trimers the
      distribution of the single-molecule population between the strongly and weakly
      fluorescent states showed no significant sensitivity to low pH, zeaxanthin, or
      low detergent conditions. The results support a unique role for LHCII trimers in
      the regulation of light harvesting by controlled fluorescence blinking and
      suggest that any contribution of the minor antenna complexes to photoprotection
      would probably involve a distinct mechanism. 

PMID- 23972854
TI  - Investigating models of protein function and allostery with a widespread
      mutational analysis of a light-activated protein.
AB  - To investigate the relationship between a protein's sequence and its biophysical
      properties, we studied the effects of more than 100 mutations in Avena sativa
      light-oxygen-voltage domain 2, a model protein of the Per-Arnt-Sim family. The A.
      sativa light-oxygen-voltage domain 2 undergoes a photocycle with a conformational
      change involving the unfolding of the terminal helices. Whereas selection studies
      typically search for winners in a large population and fail to characterize many
      sites, we characterized the biophysical consequences of mutations throughout the
      protein using NMR, circular dichroism, and ultraviolet/visible spectroscopy.
      Despite our intention to introduce highly disruptive substitutions, most had
      modest or no effect on function, and many could even be considered to be more
      photoactive. Substitutions at evolutionarily conserved sites can have minimal
      effect, whereas those at nonconserved positions can have large effects, contrary
      to the view that the effects of mutations, especially at conserved positions, are
      predictable. Using predictive models, we found that the effects of mutations on
      biophysical function and allostery reflect a complex mixture of multiple
      characteristics including location, character, electrostatics, and chemistry. 

PMID- 23972855
TI  - Structural change of DNA induced by nucleoid proteins: growth phase-specific Fis
      and stationary phase-specific Dps.
AB  - The effects of nucleoid proteins Fis and Dps of Escherichia coli on the higher
      order structure of a giant DNA were studied, in which Fis and Dps are known to be
      expressed mainly in the exponential growth phase and stationary phase,
      respectively. Fis causes loose shrinking of the higher order structure of a
      genome-sized DNA, T4 DNA (166 kbp), in a cooperative manner, that is, the DNA
      conformational transition proceeds through the appearance of a bimodal size
      distribution or the coexistence of elongated coil and shrunken globular states.
      The effective volume of the loosely shrunken state induced by Fis is 30-60 times
      larger than that of the compact state induced by spermidine, suggesting that
      cellular enzymes can access for DNA with the shrunken state but cannot for the
      compact state. Interestingly, Dps tends to inhibit the Fis-induced shrinkage of
      DNA, but promotes DNA compaction in the presence of spermidine. These
      characteristic effects of nucleotide proteins on a giant DNA are discussed by
      adopting a simple theoretical model with a mean-field approximation. 

PMID- 23972856
TI  - A computational model of reactive oxygen species and redox balance in cardiac
      mitochondria.
AB  - Elevated levels of reactive oxygen species (ROS) play a critical role in cardiac
      myocyte signaling in both healthy and diseased cells. Mitochondria represent the
      predominant cellular source of ROS, specifically the activity of complexes I and
      III. The model presented here explores the modulation of electron transport chain
      ROS production for state 3 and state 4 respiration and the role of substrates and
      respiratory inhibitors. Model simulations show that ROS production from complex
      III increases exponentially with membrane potential (DeltaPsim) when in state 4.
      Complex I ROS release in the model can occur in the presence of NADH and
      succinate (reverse electron flow), leading to a highly reduced ubiquinone pool,
      displaying the highest ROS production flux in state 4. In the presence of ample
      ROS scavenging, total ROS production is moderate in state 3 and increases
      substantially under state 4 conditions. The ROS production model was extended by
      combining it with a minimal model of ROS scavenging. When the mitochondrial redox
      status was oxidized by increasing the proton permeability of the inner
      mitochondrial membrane, simulations with the combined model show that ROS levels
      initially decline as production drops off with decreasing DeltaPsim and then
      increase as scavenging capacity is exhausted. Hence, this mechanistic model of
      ROS production demonstrates how ROS levels are controlled by mitochondrial redox
      balance. 

PMID- 23972857
TI  - Ultrasensitivity by molecular titration in spatially propagating enzymatic
      reactions.
AB  - Delineating design principles of biological systems by reconstitution of purified
      components offers a platform to gauge the influence of critical physicochemical
      parameters on minimal biological systems of reduced complexity. Here we unravel
      the effect of strong reversible inhibitors on the spatiotemporal propagation of
      enzymatic reactions in a confined environment in vitro. We use micropatterned,
      enzyme-laden agarose gels which are stamped on polyacrylamide films containing
      immobilized substrates and reversible inhibitors. Quantitative fluorescence
      imaging combined with detailed numerical simulations of the reaction-diffusion
      process reveal that a shallow gradient of enzyme is converted into a steep
      product gradient by addition of strong inhibitors, consistent with a mathematical
      model of molecular titration. The results confirm that ultrasensitive and
      threshold effects at the molecular level can convert a graded input signal to a
      steep spatial response at macroscopic length scales. 

PMID- 23972858
TI  - Detection of cochlear amplification and its activation.
AB  - The operation of the mammalian cochlea relies on a mechanical traveling wave that
      is actively boosted by electromechanical forces in sensory outer hair cells
      (OHCs). This active cochlear amplifier produces the impressive sensitivity and
      frequency resolution of mammalian hearing. The cochlear amplifier has inspired
      scientists since its discovery in the 1970s, and is still not well understood. To
      explore cochlear electromechanics at the sensory cell/tissue interface, sound
      evoked intracochlear pressure and extracellular voltage were measured using a
      recently developed dual-sensor with a microelectrode attached to a micro-pressure
      sensor. The resulting coincident in vivo observations of OHC electrical activity,
      pressure at the basilar membrane and basilar membrane displacement gave direct
      evidence for power amplification in the cochlea. Moreover, the results showed a
      phase shift of voltage relative to mechanical responses at frequencies slightly
      below the peak, near the onset of amplification. Based on the voltage-force
      relationship of isolated OHCs, the shift would give rise to effective OHC pumping
      forces within the traveling wave peak. Thus, the shift activates the cochlear
      amplifier, serving to localize and thus sharpen the frequency region of
      amplification. These results are the most concrete evidence for cochlear power
      amplification to date and support OHC somatic forces as its source. 

PMID- 23972860
TI  - Introducing titratable water to all-atom molecular dynamics at constant pH.
AB  - Recent development of titratable coions has paved the way for realizing all-atom
      molecular dynamics at constant pH. To further improve physical realism, here we
      describe a technique in which proton titration of the solute is directly coupled
      to the interconversion between water and hydroxide or hydronium. We test the new
      method in replica-exchange continuous constant pH molecular dynamics simulations
      of three proteins, HP36, BBL, and HEWL. The calculated pKa values based on 10-ns
      sampling per replica have the average absolute and root-mean-square errors of 0.7
      and 0.9 pH units, respectively. Introducing titratable water in molecular
      dynamics offers a means to model proton exchange between solute and solvent, thus
      opening a door to gaining new insights into the intricate details of biological
      phenomena involving proton translocation. 

PMID- 23972859
TI  - Coupled reversible and irreversible bistable switches underlying TGFbeta-induced
      epithelial to mesenchymal transition.
AB  - Epithelial to mesenchymal transition (EMT) plays an important role in embryonic
      development, tissue regeneration, and cancer metastasis. Whereas several feedback
      loops have been shown to regulate EMT, it remains elusive how they coordinately
      modulate EMT response to TGF-beta treatment. We construct a mathematical model
      for the core regulatory network controlling TGF-beta-induced EMT. Through
      deterministic analyses and stochastic simulations, we show that EMT is a
      sequential two-step program in which an epithelial cell first is converted to
      partial EMT then to the mesenchymal state, depending on the strength and duration
      of TGF-beta stimulation. Mechanistically the system is governed by coupled
      reversible and irreversible bistable switches. The SNAIL1/miR-34 double-negative
      feedback loop is responsible for the reversible switch and regulates the
      initiation of EMT, whereas the ZEB/miR-200 feedback loop is accountable for the
      irreversible switch and controls the establishment of the mesenchymal state.
      Furthermore, an autocrine TGF-beta/miR-200 feedback loop makes the second switch
      irreversible, modulating the maintenance of EMT. Such coupled bistable switches
      are robust to parameter variation and molecular noise. We provide a mechanistic
      explanation on multiple experimental observations. The model makes several
      explicit predictions on hysteretic dynamic behaviors, system response to pulsed
      stimulation, and various perturbations, which can be straightforwardly tested. 

PMID- 23972861
TI  - Effect of hay dust extract and cyathostomin antigen stimulation on cytokine
      expression by PBMC in horses with recurrent airway obstruction.
AB  - Equine recurrent airway obstruction (RAO) is an inflammatory, obstructive airway
      disease induced by exposure of susceptible horses to inhaled organic dust
      particles. The immunological process underlying RAO is still unclear. Previous
      studies have shown that RAO is linked to the Interleukin-4 receptor (IL-4R) gene
      in one Warmblood family (F1), but not in another (F2). It has also been shown
      that in F1, but not in F2, RAO is associated with resistance against parasites,
      suggesting that this association may have an immuno-genetic basis. Therefore, we
      hypothesized that the T helper (h)1/Th2/regulatory (Treg) cytokine profiles of
      RAO-associated antigen- and parasite-antigen-stimulated peripheral blood
      mononuclear cells (PBMC) differ between RAO-affected and healthy horses depending
      on their genetic background. In our study, PBMC from 17 RAO-affected and 14
      healthy control horses of F1 and F2 were stimulated for 24h with antigens
      relevant to RAO [hay dust extract (HDE), Aspergillus fumigatus extract (AFE) and
      lipopolysaccharids (LPS)]; cyathostomin extract (CE) and recombinant cyathostomin
      antigen (RCA) or with concanavalin A (ConA). Total mRNA levels of IL-4, IL-4R, IL
      13, interferon (INF)-gamma and IL-10 were examined by qRT-PCR. Stimulation with
      either HDE or RCA resulted in significant differences in IL-4R mRNA levels
      between RAO-affected and control horses in F1, but not in F2. For IL-10 mRNA
      expression, a significant difference between RAO-affected and control horses in
      F1 but not in F2 was observed only following stimulation with HDE. In contrast to
      HDE, stimulation with CE resulted in a significant difference of IL-10 mRNA
      expression level between RAO-affected horses of F2 and healthy horses of F1. No
      significant differences were detected upon stimulation with any of the other
      challenge agents. These findings indicate that the immunological response,
      specifically IL-4R expression, in response to hay dust and cyathostomin antigens,
      differs between RAO-affected and healthy horses depending on their genetic
      background. This study shows that analysis of PBMC reveals systemic changes
      associated with RAO and helps to elucidate immunological pathways involved in
      this disease. 

PMID- 23972862
TI  - Cory Monteith dies of a heroin overdose at age 31.

PMID- 23972863
TI  - A study on the correlation between the nurses' and patients' postoperative pain
      assessments.
AB  - In this research, the correlation of assessment of postoperative pain between
      nurses and their clients is investigated. The aim of the research was to
      investigate whether or not the nurses can evaluate the pain that clients have in
      the postoperative process in the same sense as clients do and to examine personal
      factors that affect this evaluation. The descriptive and comparative research was
      undertaken between January 2008 and April 2008 in the clinics of Cukurova
      University Balcali Hospital. The study group consisted of 47 nurses and 94
      patients aged 18-65 years evaluated in the 48 hours' postoperative period. After
      review of the literature regarding McGill-Melzack pain assessment, a
      questionnaire for patients and another for nurses were used. The data gathered
      from the surveys were analyzed by the SPSS program. For intermittent variables
      chi-square test, for denomination variables kappa, and for sequent variables
      congruity gamma factors were used. At the end of the research, the correlation
      between the patient scores and the nurse scores that were gathered from first,
      second, third, and fourth parts of the pain evaluation documents were observed:
      part 1, Gamma = 290, p = .063; part 3/1-2, Gamma = 380, p = .008, 3/1; part 3,
      Gamma = 357, p = .007; part 3/2, Gamma = 209, p = .031; part 4, Gamma = 346, p <
      .001. The congruity points obtained from the statistical data contrast with the
      literature, showing that the nurses and the patients evaluated the postoperative
      pain in the same sense. Pain evaluation investigations are recommended to be done
      with the attendance of more nurses and patients, and their results should be
      shared with all nurses.

PMID- 23972864
TI  - The effects of self-pain management on the intensity of pain and pain management
      methods in arthritic patients.
AB  - The aims of this study were to investigate the effects of pain management
      education on the intensity of pain and frequency of utilization of pain
      management methods in two groups of patients with arthritis of different
      pathogenesis and clinical features, and to compare whether a significant
      difference existed between the two groups. The study was carried out between
      September 2007 and June 2008 on 30 female patients with gonarthrosis and 30
      female patients with rheumatoid arthritis (RA) followed at the rheumatology
      outpatient clinic of a university hospital. Data on sociodemographic
      characteristics and those related with the illness were collected using a special
      survey. Each patient was given information about the features, causes, and
      treatment of the arthritis and how to cope with pain, emphasizing the importance
      of pain management methods. The intensity of pain and efficacy of pain management
      methods were assessed using the McGill Pain Questionnaire and the Pain Management
      Inventory at baseline and the second and sixth weeks after the education. The
      SPSS (v15.0) statistical package was used for statistical analysis. After
      education, significant improvements in pain intensity scores compared with
      baseline scores were observed in both groups (p < .05), and there was no
      significant difference between the RA and gonarthrosis groups. Among the various
      pain management methods, the education program led to significantly more
      utilization of massaging the painful area, exercising, and using complementary
      methods to control stress in both groups of patients, and there was no
      significant difference between the groups. In conclusion, the pain management
      education given in this study alleviated the intensity of pain and significantly
      increased the use of some pain management methods in both gonarthrosis and RA
      cases. 

PMID- 23972865
TI  - The effect of relaxation techniques and back massage on pain and anxiety in
      Turkish total hip or knee arthroplasty patients.
AB  - The purpose of this study was to examine the effects of relaxation techniques and
      back massage on postoperative pain, anxiety, and vital signs on postoperative
      days 1-3 in patients who had undergone total hip or knee arthroplasty (THA, TKA).
      Sixty patients having a THA or TKA were randomly assigned to either a
      experimental group or a control group. The McGill Pain Questionnaire Short Form
      (MPQ-SF) and State Anxiety Inventory (SAI) were used to measure pain and anxiety,
      respectively. Vital signs, including blood pressure (systolic and diastolic),
      pulse, and respiratory rate, were also obtained. Statistically significant
      differences in pain intensity (F = 14.50; p = .000), anxiety level (F = 19.13; p
      = .000), and vital signs (F = 169.61, 9.14, 14.23, 65.64; p = .000) measured over
      time were found between the experimental and the control group. Results of this
      research provide evidence to support the use of relaxation techniques and back
      massage at bed rest times of patients to decrease pain and anxiety. The
      interventions helped them to forget about their pain for a while and improved
      their anxiety state. After an evaluation of the conclusions, use of these
      interventions should be implemented by nurses into routine plans of care for
      patients. 

PMID- 23972866
TI  - Prescribed opioids adherence among Taiwanese oncology outpatients.
AB  - The purpose of this study was to evaluate adherence to prescribed opioids in
      Taiwanese oncology outpatients and to examine the associations between various
      demographic and medical characteristics and prescribed opioids adherence. Ninety
      two outpatients who had taken prescribed opioid analgesics for cancer-related
      pain at least once in the past week participated in this study. Patients were
      asked to recall the dose of each opioid analgesic that they had taken in the past
      24 hours. Mean adherence rates were calculated for analgesic adherence. For mean
      adherence rates, all opioid analgesics were converted to morphine equivalents.
      The results of this study reveal a priority issue of poor opioid analgesic
      adherence. The adherence rate of 63.6% for the around-the-clock opioid analgesics
      in this study is well below acceptable levels. Also, an adherence rate of 30.9%
      for the as-needed opioid analgesics is very low. This study identified that women
      tend to be less adherent to their prescribed opioid analgesic regimen than men.
      Findings of this study suggest that to improve pain control, efforts to promote
      patients' opioid regimen adherence should be given high priority. Clinicians
      should be particularly aware that there may be some gender difference in
      adherence to prescribed opioid analgesics. There is a need for better
      programmatic efforts to improve analgesic adherence. 

PMID- 23972867
TI  - A narrative review of the impact of disbelief in chronic pain.
AB  - Although the experience of being believed is frequently alluded to in chronic
      pain literature, few studies have specifically explored this phenomenon and even
      fewer reviews have been offered. This narrative review sought to explore the
      wider social context in which individuals with chronic pain may experience
      disbelief toward their pain. Articles were obtained through a search of eight
      databases and a hand search of the references of full-text papers. Key results
      within the articles were noted and integrated to form three main themes: stigma,
      the experience of isolation, and the experience of emotional distress. The
      experience of stigma can occur in a number of ways. It may be through actual or
      perceived encounters with others; it can be through the use of psychologic
      explanations of pain; it can come through a perceived challenge to one's
      integrity and subsequently affect an individual's identity; and such stigma may
      be influenced by negative female stereotypes. The loss of relationships
      associated with being disbelieved can lead to the experience of isolation. This
      may be self-initiated, particularly when an individual has been given a contested
      diagnosis. Finally, disbelief can lead to emotional distress. This can take the
      form of guilt, depression, and anger. Throughout the article, implications for
      health care professionals, working with individuals living with chronic pain, are
      discussed. 

PMID- 23972868
TI  - American Society for Pain Management Nursing position statement: pain management
      at the end of life.
AB  - Pain at the end of life continues to be of great concern as it may be
      unrecognized or untreated. While nurses have an ethical obligation to reduce
      suffering at the end of life, barriers remain regarding appropriate and adequate
      pain management at the end of life. This position statement from the American
      Society for Pain Management Nursing contains recommendations for nurses,
      prescribers, and institutions that would improve pain management for this
      vulnerable population. 

PMID- 23972869
TI  - American Society for Pain Management Nursing position statement with clinical
      practice guidelines: authorized agent controlled analgesia.
AB  - The American Society for Pain Management Nursing (ASPMN) has updated its 2007
      position statement on the use of authorized agent controlled analgesia (AACA) for
      patients who are unable to independently utilize patient-controlled analgesia
      (PCA). ASPMN continues to support the use of AACA to provide timely and effective
      pain management while promoting equitable care for vulnerable patient populations
      who are unable to utilize PCA. ASPMN does not support the use of "PCA by Proxy"
      in which unauthorized individuals activate PCA for a patient. The background of
      the development of the position statement, definitions related to AACA, and
      application of ethical principles to the use of AACA are presented in the
      document. This position statement includes an updated review of the evidence
      related to AACA and a call for further research. Clinical practice
      recommendations for authorized agents, nurses, prescribers, and organizations are
      provided with an emphasis on the importance of appropriate authorized agent
      selection, education, diligent patient assessment and medication management. 

PMID- 23972870
TI  - Establishing the validity and reliability of a pediatric pain knowledge and
      attitudes questionnaire.
AB  - Children continue to experience unrelieved pain during hospitalization, despite
      the evidence to guide nurses' pain management practices being readily available.
      Nurses' knowledge and attitudes have been identified as a possible reason for
      suboptimal pain management. This study examines the validity and reliability of
      an existing questionnaire to validate it for use in the population of interest.
      Initial testing demonstrated low reliability and validity. Modifications to the
      questionnaire were made on the basis of these results and the feedback provided
      by experts in pediatric pain management. Subsequent testing demonstrated good
      validity and reliability, suggesting that the questionnaire is appropriate for
      measuring nurses' knowledge and attitudes in relation to pediatric pain
      management. 

PMID- 23972871
TI  - Information-seeking coping behaviors during painful procedures in African
      American children with sickle cell disease.
AB  - This study examined the frequency of information-seeking coping behaviors in 37
      African-American children (ages 5-17 years) with sickle cell disease during
      venipuncture. The relationships between coping behaviors and child- and parent
      reported pain and observational distress were also assessed. The majority of
      children attended to the procedure, but did not seek information via questions.
      This pattern of coping was only partially effective at reducing distress and had
      no relation to pain. This pattern of coping is discussed within the context of
      cultural factors that may be important in understanding responses to procedural
      pain in pediatric sickle cell disease. 

PMID- 23972872
TI  - Nursing ward managers' perceptions of pain prevalence at the aged-care facilities
      in Japan: a nationwide survey.
AB  - This study aimed to examine nursing ward managers' perceptions of pain prevalence
      among older residents and the strategies of pain management at the Health Service
      Facilities for the Elderly Requiring Care (HSFERC) in Japan and to investigate
      the factors related to the prevalence. Nursing ward managers in 3,644 HSFERC were
      asked to participate in this study. Questionnaires were sent to them regarding
      pain prevalence among the older residents in their wards, their provisions for
      pain care, and other pain management strategies. The perceived pain prevalence
      factors were examined statistically. The final sample comprised 439 participants
      (12.0%). A total of 5,219 residents (22.3%) were recognized as suffering from
      pain on the investigation day. Only 8 wards (1.8%) used pain management
      guidelines or care manuals, and 14 (3.2%) used a standardized pain scale. The
      ward managers' age (p = .008) and nursing experience (p = .006) showed a
      significant negative association with pain prevalence estimation. Moreover, there
      was a significant association between the groups' pain prevalence estimation and
      the nursing managers' beliefs that older adults were less sensitive to pain (p =
      .01), that pain was common among older people (p = .007), and that the time to
      treat residents' pain was insufficient (p = .001). The ward managers' perceptions
      regarding pain prevalence varied; the perceived pain rates were possibly lower
      than the actual percentages. Insufficient pain management strategies at the
      HSFERC were also suggested. An appropriate pain management strategy for Japanese
      aged care and its dissemination are urgently required.

PMID- 23972873
TI  - Opioid-induced hyperalgesia: is it clinically relevant for the treatment of pain
      patients?
AB  - There is a curious and paradoxic phenomenon, reliably demonstrated in animal
      models, that consists of an increased sensitivity to pain that is apparently
      induced by the very opioid drugs used to ameliorate the pain. This phenomenon is
      termed "opioid-induced hyperalgesia." Whether opioid-induced hyperalgesia occurs
      in humans, and, if so, to what extent and consequence, is far less established.
      This is a critical question for attempting to treat pain. If opioid-induced
      hyperalgesia develops in a patient, it would masquerade as tolerance (because the
      clinical effectiveness of the opioid would be diminished), yet the appropriate
      clinical adjustment would be precisely the opposite to that of tolerance. It
      would be to decrease, rather than increase, the dose of opioid. We review the
      evidence, particularly the clinical evidence, about opioid-induced hyperalgesia
      and the postulated mechanisms. We conclude that given the clinical ramifications,
      opioid-induced hyperalgesia is one of the most understudied important aspects of
      opioid research. 

PMID- 23972874
TI  - Administering ziconotide and monitoring patients treated with ziconotide: expert
      opinions.
AB  - Some patients with chronic pain who are intolerant of or refractory to treatment
      with systemic analgesics may benefit from intrathecal therapy. Ziconotide is the
      first nonopioid analgesic approved by the United States Food and Drug
      Administration for intrathecal administration. Several randomized, double-blind,
      placebo-controlled clinical trials have demonstrated the efficacy and safety of
      ziconotide. However, the maximum recommended dosing and titration schedule
      provided in the prescribing information may be too aggressive for some patients,
      and experience has demonstrated that ziconotide is better tolerated with slower
      titration to a lower maximum dose. Efficacy can be assessed by an evaluation of
      changes in pain, functionality, and quality of life. Cognitive adverse events may
      be subtle; therefore, it is important that health care professionals not only
      monitor patients for signs and symptoms of cognitive adverse events, but also
      teach family members how to do the same. Careful patient assessment and
      monitoring can help optimize the potential benefit from treatment with
      ziconotide. 

PMID- 23972891
TI  - Final incision size after cataract surgery with toric intraocular lens
      implantation using 2 techniques.
AB  - PURPOSE: To analyze the changes in incision sizes after implantation of a toric
      intraocular lens (IOL) using 2 methods. SETTING: Department of Ophthalmology,
      Clinica Universidad de Navarra, Pamplona, Spain. DESIGN: Prospective case series.
      METHODS: Coaxial phacoemulsification and IOL implantation through a 2.2 mm clear
      corneal incision using a cartridge injector were performed. Wound-assisted or
      cartridge-insertion techniques were used to implant the IOLs. The results were
      analyzed according to IOL spherical and cylindrical powers. Corneal hysteresis
      (CH) and the corneal resistance factor (CRF) were measured and evaluated based on
      the changes in incision size. RESULTS: Incision size increased in 30 (41.7%) of
      72 eyes in the wound-assisted group and 71 (98.6%) of 72 eyes in the cartridge
      insertion group. The mean incision size after IOL implantation was 2.27 mm +/-
      0.06 (SD) and 2.37 +/- 0.05 mm, respectively (P<.01). The final incision size and
      IOL spherical power in the wound-assisted technique group (P=.02) and the
      cartridge-insertion technique group (P=.03) were correlated significantly; IOL
      toricity was not (P=.19 and P=.28, respectively). The CH and CRF values were not
      correlated with the final incision size. CONCLUSIONS: The final incision size and
      the changes in incision size after IOL implantation were greater with the
      cartridge-insertion technique than with the wound-assisted technique. The
      increase was related to IOL spherical power in both groups but not to IOL
      toricity. Corneal biomechanical properties were not correlated with the final
      incision size.

PMID- 23972892
TI  - Assessment of midperipheral anterior chamber depth in patient with posterior
      chamber phakic intraocular lens.
AB  - We describe a patient who required surgical explantation of a phakic intraocular
      lens (pIOL) as a result of mechanical angle closure despite the absence of
      standard preoperative risk factors. An assessment of the patient's records
      suggested peripheral anterior chamber depth (ACD) values considerably shallower
      than the central ACD measurement. Subsequently, the midperipheral values of all
      patients having pIOL implantation at our practice were reviewed to provide
      potential baseline measurements for comparison against the values of the
      explanted pIOL eyes. Assessment of midperipheral anterior chamber anatomy may be
      advantageous in the evaluation of patients for pIOL surgery. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 23972893
TI  - Axis difference between corneal and internal astigmatism to consider for toric
      intraocular lenses.
AB  - PURPOSE: To evaluate the axis difference between corneal and internal astigmatism
      in patients with cataract, because if the axis of corneal astigmatism is opposite
      to the axis of internal astigmatism, the amount of refractive astigmatism will
      increase after cataract surgery owing to disappearance of the neutralizing effect
      of the crystalline lens on corneal astigmatism. DESIGN: Retrospective cross
      sectional study. METHODS: One hundred eighty patients (180 eyes) who underwent
      cataract surgery were enrolled. Preoperative refractive, corneal, and internal
      astigmatism were measured using a wavefront analyzer and retrospectively
      analyzed. On-axis was defined as an axis difference between corneal and internal
      astigmatism of 180 +/- 10 degrees. Opposite-axis was defined as an axis
      difference between corneal and internal astigmatism of 90 +/- 10 degrees. The
      remaining cases were defined as oblique-axis. RESULTS: Corneal and internal
      astigmatic vectors showed a tendency to have the opposite direction. An on-axis
      difference was seen in 10.0% of patients (18 eyes), oblique-axis in 69.4% of
      patients (125 eyes), and opposite-axis in 20.6% of patients (37 eyes). Of all
      eyes, 10.0% had an opposite-axis difference with more than 1.00 diopter (D) of
      both corneal and internal astigmatism. The percentage of eyes with an opposite
      axis difference between corneal and internal astigmatism had a tendency to
      increase as corneal and internal astigmatism increased (P = .030 and P = .003,
      respectively). CONCLUSIONS: A total of 10.0% of all eyes with cataract had an
      opposite-axis difference with more than 1.00 D of both corneal and internal
      astigmatism. In these cases, surgical techniques to reduce corneal astigmatism,
      such as a toric intraocular lens, should be recommended to increase patient
      satisfaction.

PMID- 23972894
TI  - Conjunctival mini-flap operation for restrictive strabismus after periocular
      surgery.
AB  - PURPOSE: To investigate the effect of conjunctival mini-flap operation to treat
      restrictive strabismus in patients with diplopia caused by conjunctival adhesion
      and hyperplasia after periocular surgery. DESIGN: Case series study. METHODS:
      Eleven patients with diplopia and restrictive strabismus attributable to
      conjunctival dysplasia after periocular surgery underwent a conjunctival mini
      flap surgery without a muscle operation and were followed-up at 1, 3, and 6
      months after surgery. The Hess screen test, binocular single vision field with
      Goldmann perimetry, and extraocular muscle movement were analyzed pre- and post
      operatively. Patient satisfaction with the cosmetic results of conjunctival mini
      flap operation was also investigated. RESULTS: The mean preoperative alignment
      deviation in primary position was 10.4 +/- 5.6 prism diopters (PD). Diplopia in
      the primary position was resolved in 95% of the patients. The mean postoperative
      deviation was 1.36 +/- 2.34 PD at the primary position. No significant
      complications or recurrences were noted after mean 9.5 +/- 4.2 months follow-up.
      CONCLUSION: Conjunctival mini-flap operation is an effective and safe surgical
      technique for treating patients with diplopia and restrictive strabismus
      following periocular surgery.

PMID- 23972895
TI  - Macular structure parameters as an automated indicator of paracentral scotoma in
      early glaucoma.
AB  - PURPOSE: To evaluate the predictive ability of macular parameters defined in the
      significance map created using spectral-domain optical coherence tomography (SD
      OCT) for paracentral visual field defects in early glaucoma. DESIGN: Prospective
      comparative study. METHODS: We studied 78 early-glaucomatous eyes of 78 patients,
      who underwent SD-OCT and standard automated perimetry 10-2. Macular layer
      parameters included the retinal nerve fiber layer (RNFL), ganglion cell layer
      (GCL) + inner plexiform layer (IPL), and RNFL + GCL + IPL. The minimal distance
      between the area with abnormal (P < 1%) thickness and foveal center was defined
      as the shortest distance. A wider area of an abnormally thinned (<1%) region,
      within either an inferior or a superior hemicircle with a diameter of 6 mm
      centered at the fovea, was defined as the macular abnormal area. A
      circumpapillary RNFL parameter was defined in its 36 sectors. Areas under the
      receiver operating characteristic curves (ROCs) were calculated to discriminate
      between eyes with (n = 39) and without (n = 39) paracentral visual field defects
      in the central 5 degrees. RESULTS: Measurement reproducibility was almost perfect
      in the macular parameters at P < 1% (intraclass correlation, 0.907-0.942). Areas
      under the ROC were significantly higher (P <= 0.01) in the macular parameters
      (0.870-0.930), including the shortest distance of GCL + IPL/RNFL + GCL + IPL, and
      the macular abnormal area of RNFL/GCL + IPL/RNFL + GCL + IPL than in the
      circumpapillary RNFL parameter (0.676). When specificity was fixed at >=90%, the
      shortest distance of GCL + IPL (area under the ROC = 0.874) and the macular
      abnormal area of RNFL (area under the ROC = 0.894) showed sensitivities greater
      than 50%. CONCLUSIONS: Macular structural parameters defined on an SD-OCT
      significance map may be potentially useful predictors of the presence of
      paracentral scotoma.

PMID- 23972896
TI  - Polycyclic aromatic hydrocarbon biomarkers and serum markers of inflammation. A
      positive association that is more evident in men.
AB  - BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are potent atmospheric
      pollutants, occurring from anthropogenic and natural sources. Several animal
      studies have reported a positive association of PAHs with inflammation. However,
      it is not clear if lower background exposure to PAHs is associated with
      inflammation in humans, independent of smoking, a major source of PAHs. METHODS:
      We examined participants from the National Health and Nutrition Examination
      Survey 2001-2002, 2003-2004, and 2005-2006. Our exposures of interest were eight
      urinary monohydroxy polycyclic aromatic hydrocarbon biomarkers. Our outcomes were
      serum markers of inflammation; C-reactive protein (CRP) (<=10 mg/L) and total
      white blood cell (WBC) count (4000-12,000 cells/MUL). RESULTS: Compared to
      participants with summed biomarkers of low-molecular weight (LMW) PAHs in the
      lowest quartile, the multivariable odds ratios (95% confidence interval) of high
      serum CRP (>=3 mg/L) and high total WBC count (defined as at or above the 95
      percentile of total WBC distribution) among participants in the highest exposure
      quartile were 1.77 (1.13, 2.76) and 1.34 (1.12, 1.60) respectively. Urinary 1
      hydroxypyrene, the biomarker of the higher molecular weight pyrene, was
      positively associated with total WBC count, and to lesser extent with serum CRP.
      In subsequent analyses, the positive association between LMW PAHs and serum CRP
      and total WBC count was found to be present within the stratified subgroups,
      independent of smoking and other potential confounders. The positive association
      was more evident among adult males when compared to females. CONCLUSIONS: Urinary
      PAH biomarkers were found to be positively associated with serum CRP and total
      WBC count independent of smoking and other potential confounders. The association
      was more evident in men.

PMID- 23972897
TI  - Letter to the editor: regarding "individual and neighborhood correlates of
      membership in drug-using networks with a higher prevalence of HIV in New York
      City (2006-2009)".

PMID- 23972898
TI  - Response to letter to the editor: regarding "individual and neighborhood
      correlates of membership in drug-using networks with a higher prevalence of human
      immunodeficiency virus (2006-2009)".

PMID- 23972899
TI  - Is epidemiology correcting its vision problem? A perspective on our perspective:
      2012 presidential address for American College of Epidemiology.
AB  - Epidemiology, like all disciplines, exists within and is shaped by a culture that
      frames its ways of understanding. In the last 60 years epidemiology as a
      discipline and scientific approach has undergone major transition, but remains
      challenged by vestiges of the limiting frameworks of our origins which shape the
      way we approach questions, and even the questions we choose to investigate. A
      part of the current transformation is a reframing of our perspective and a
      broadening of our methods to encourage creativity and to encompass new types of
      evidence and new approaches to investigation and interpretation. Epidemiologists
      are developing innovative ways to approach increasingly complex problems and
      becoming more open to multi-disciplinary approaches to solving epidemiologic
      challenges. 

PMID- 23972900
TI  - Measuring the levels of noise at the Istanbul Ataturk Airport and comparisons
      with model simulations.
AB  - Airport noise and its impact on the surrounding areas are major issues in the
      aviation industry. The Istanbul Ataturk Airport is a major global airport with
      passenger numbers increasing rapidly per annum. The noise levels for day, evening
      and night times were modeled around the Istanbul Ataturk Airport according to the
      European Noise Directive using the actual data records for the year 2011. The
      "ECAC Doc. 29-Interim" method was used for the computation of the aircraft
      traffic noise. In the setting the noise model for the local airport topography
      was taken into consideration together with the noise source data, the airport
      loadings, features of aircraft and actual air traffic data. Model results were
      compared with long-term noise measurement values for calibration. According to
      calibration results, classifications of the aircraft type and flight tracks were
      revised. For noise model validation, the daily noise measurements at four
      additional locations were used during the verification period. The input data was
      re-edited only for these periods and the model was validated. A successful model
      performance was obtained in several zones around the airport. The validated noise
      model of the Istanbul Ataturk Airport can be now utilized both for determining
      the noise levels in the future and for producing new strategies which are about
      the land use planning, operational considerations for the air traffic management
      and the noise abatement procedures. 

PMID- 23972901
TI  - Source- and region-specific distribution of polycyclic aromatic hydrocarbons in
      sediments from Jinhae Bay, Korea.
AB  - This study surveyed polycyclic aromatic hydrocarbons (PAHs) at 80 sites in
      sediment from Jinhae Bay, which consists of Masan Bay (MSB), Haengam Bay (HAB),
      Bay Proper (JBP), Wonmoon Bay (WMB), and Gohyun Bay (GHB). Levels of the EPA 16
      priority PAHs, 5 groups of alkylated PAH homologues and 2 biogenic PAHs were
      determined. Total PAHs (sum of all target PAHs) ranged from 37.0 ng/g to 3,110
      ng/g with a mean of 339 ng/g. WMB had the highest concentration (473 +/- 665
      ng/g: average +/- standard deviation) followed by GHB (214 +/- 141 ng/g), MSB
      (175 +/- 358 ng/g), JBP (133 +/- 86.0 ng/g) and HAB (118 +/- 129 ng/g). A tiered
      source identification approach using the pyrogenic index, PAH isomer ratios and
      alkylated PAH double ratios found that both pyrogenic and petrogenic PAHs were
      dominant, and identified three different source- and region-specific groups.
      Input pathway tracers, such as butyltins, nonylphenols and dibenzothiophenes,
      were used to track the main input pathways. A shipyard and urban runoff were
      identified as the major input pathways of PAHs into GHB, and urban runoff was
      identified as a major pathway into MSB and WMB. Used crankcase oil, diesel
      exhaust, tyre debris and asphalt were considered to be the dominant PAH sources
      in urban runoff. Several PAH compounds exceeded the interim marine sediment
      quality guidelines for the protection of aquatic environments, among which
      dibenz[a,h]anthracene exceeded the guidelines in 16% of surveyed sites. Current
      PAH levels in MSB indicated an improving situation following the implementation
      of a total pollutant load management system (TPLMS); this is in accordance with
      other studies. WMB was recognised as an area of concern within this bay,
      suggesting the update of the TPLMS in this region.

PMID- 23972902
TI  - Yu's flap for lower lip and reverse Yu's flap for upper lip reconstruction: 20
      years experience.
AB  - Reconstruction of defects of the lip caused by cancer with its requirements of a
      complicated anatomical structure, important physiological function, and
      acceptable cosmetic result, is a challenge for oral and maxillofacial and plastic
      surgeons. A method that combines rotation and advancement flaps was described by
      Yu in 1989 for the reconstruction of defects of the lower lip. In our department
      between January 1992 and December 2012, 8 patients had reverse Yu flaps for the
      reconstruction of upper lip defects and 56 patients had classic Yu flaps for
      lower lip defects. Patients with defects located laterally to the upper lips,
      ranging from 1/3 to 1/2, had unilateral reverse Yu flaps, and bilateral
      procedures were done for defects of less than 2/3 of the lips. However, if the
      defects were located in the centre of the upper lips, between 1/3 and 1/2, they
      were treated with bilateral reverse Yu flaps. Patients with defects between 1/3
      and 2/3 of lower lips had unilateral Yu flaps, and if the defects were wider than
      2/3 of the lower lips, the procedure was bilateral. No flap failed and desirable
      functional and aesthetic outcomes were recorded in all cases. Here we report our
      experience with the Yu flap for the benefit of other surgeons.

PMID- 23972903
TI  - Maternal separation is associated with DNA methylation and behavioural changes in
      adult rats.
AB  - Early life stress is known to promote long-term neurobiological changes, which
      may underlie the increased risk of psychopathology. Maternal separation (MS) is
      used as an early life stressor that causes profound neurochemical and behavioural
      changes in the pups that persist into adulthood. However, the exact mechanism of
      how MS alters these behavioural changes is not yet understood. Epigenetic
      modifications, such as DNA methylation, are critical regulators of persistent
      gene expression changes and may be related to behavioural disorders. The aim of
      the present study was to investigate whether early life stress on rats could
      alter cocaine-induced behavioural sensitisation in adulthood via aberrant DNA
      methylation. We have three main findings: (1) MS increased DNA methyltransferases
      (DNMTs) expression in the nucleus accumbens (NAc) of infant and adult rats; (2)
      MS induced DNA hypomethylation on a global level in the NAc, and hypermethylation
      of the promoter regions of the protein phosphatase 1 catalytic subunit (PP1C) and
      adenosine A2Areceptor (A2AR) genes, which was associated with their
      transcriptional downregulation in the NAc; (3) MS-induced molecular changes
      paralleled an increased response to cocaine-induced locomotor activity and
      exploratory behaviour in adult rats. Thus, our results suggest that stressful
      experiences in early life may create a background, via aberrant DNA methylation,
      which promotes the development of cocaine-induced behavioural sensitisation in
      adulthood. 

PMID- 23972904
TI  - Oral and sublingual immunotherapy for food allergy: current progress and future
      directions.
AB  - Food allergies are increasing in prevalence and present an emerging epidemic for
      westernized countries. Strict dietary avoidance is the only approved management
      for food allergy, but accidental exposures regularly occur, leading to
      significant patient anxiety and decreased quality of life. Over the past decade,
      oral and sublingual immunotherapies have emerged as potential treatments for food
      allergy. While several small clinical trials have demonstrated that immunotherapy
      can desensitize food-allergic individuals, strategies for further enhancing
      safety and definitively establishing long-term efficacy are needed. This review
      presents an overview of recent oral and sublingual immunotherapy trials, and
      provides a glimpse into what the next generation of food immunotherapy may
      entail. 

PMID- 23972905
TI  - Design of the SHAPE-2 study: the effect of physical activity, in addition to
      weight loss, on biomarkers of postmenopausal breast cancer risk.
AB  - BACKGROUND: Physical inactivity and overweight are two known risk factors for
      postmenopausal breast cancer. Former exercise intervention studies showed that
      physical activity influences sex hormone levels, known to be related to
      postmenopausal breast cancer, mainly when concordant loss of body weight was
      achieved. The question remains whether there is an additional beneficial effect
      of physical activity when weight loss is reached. DESIGN: The SHAPE-2 study is a
      three-armed, multicentre trial. 243 sedentary, postmenopausal women who are
      overweight or obese (BMI 25-35 kg/m2) are enrolled. After a 4-6 week run-in
      period, wherein a baseline diet is prescribed, women are randomly allocated to
      (1) a diet group, (2) an exercise group or (3) a control group. The aim of both
      intervention groups is to lose an amount of 5-6 kg body weight in 10-14 weeks.
      The diet group follows an energy restricted diet and maintains the habitual
      physical activity level. The exercise group participates in a 16-week endurance
      and strength training programme of 4 hours per week. Furthermore, they are
      prescribed a moderate caloric restriction. The control group is asked to maintain
      body weight and continue the run-in baseline diet. DISCUSSION: This study will
      give insight in the potential attributable effect of physical activity on breast
      cancer risk biomarkers and whether this effect is mediated by changes in body
      composition, in postmenopausal women. Eventually this may lead to the design of
      specific lifestyle guidelines for prevention of breast cancer. TRIAL
      REGISTRATION: The SHAPE-2 study is registered in the register of
      clinicaltrials.gov, Identifier: NCT01511276.

PMID- 23972906
TI  - Nurse led care coordination: trial protocol and development of a best practice
      resource guide for a cluster controlled clinical trial in Australian aged care
      facilities.
AB  - In this paper we describe (i) the protocol for a cluster controlled clinical
      trial of nurse led care coordination in residential aged care facilities (RACF);
      and (ii) the development and content of a best practice resource guide to be
      implemented as part of this trial. We used published systematic reviews of
      quantitative studies, existing resources and multidisciplinary expert opinion to
      develop an intervention for testing in a cluster controlled trial (Australian and
      New Zealand Clinical Trials Registry Number 12611000933954). The trial will
      determine whether care coordination of multiple evidenced based strategies can
      improve quality of life and reduce hospitalization rates amongst people living in
      RACF. Central to the intervention arm of the trial are two components: (i)
      experienced nurse practitioners responsible for resident care and (ii) a best
      practice guide for the care processes being delivered and coordinated by those
      nurses. In this paper we outline how this practice guide, which is published
      herein, was refined through consultative processes and practitioner testing. 

PMID- 23972907
TI  - Enhanced cytotoxicity of pentachlorophenol by perfluorooctane sulfonate or
      perfluorooctanoic acid in HepG2 cells.
AB  - Chlorinated phenols and perfluoroalkyl acids (PFAAs) are two kinds of pollutants
      which are widely present in the environment. Considering liver is the primary
      toxic target organ for these two groups of chemicals, it is interesting to
      evaluate the possible joint effects of them on liver. In this work, the combined
      toxicity of pentachlorophenol (PCP) and perfluorooctane sulfonate (PFOS) or
      perfluorooctanoic acid (PFOA) were investigated using HepG2 cells. The results
      indicated that PFOS and PFOA could strengthen PCP's hepatotoxicity. Further
      studies showed that rather than intensify the oxidative stress or promote the
      biotransformation of PCP, PFOS (or PFOA) might lead to strengthening of the
      oxidative phosphorylation uncoupling of PCP. By measuring the intracellular PCP
      concentration and the cell membrane properties, it was suggested that PFOS and
      PFOA could disrupt the plasma membrane and increase the membrane permeability.
      Thus, more cellular accessibility of PCP was induced when they were co-exposed to
      PCP and PFOS (or PFOA), leading to increased cytotoxicity. Further research is
      warranted to better understand the combined toxicity of PFAAs and other
      environmental pollutants. 

PMID- 23972908
TI  - Monitoring of heavy metal and organic compound levels along the Eastern Aegean
      coast with transplanted mussels.
AB  - Within the framework of the MYTITURK project, heavy metals and organic compounds
      contaminations were assessed in transplanted mussels in eight different bays from
      the Eastern Aegean coast. Izmir Bay, Canakkale Strait entrance, Saros and
      Candarli Bay were defined low pollution extent according to Principal Component
      Analysis taking into metal accumulation. PAHs (Polycyclic Aromatic Hydrocarbons)
      levels in the range of 29.4-64.2 ng g(-1) (dry weight) indicated that PAH
      contamination level classified as low along the Aegean coast. Concentrations of
      Aroclor1254 and 1260 were higher in transplanted mussels from Canakkale Strait
      Outlet due to industrial activities was originated from Marmara Sea. The
      organochlorinated pesticides such as heptachlor (<0.4 ng g(-1)), aldrin (<0.30 ng
      g(-1)), dieldrin (<0.75 ng g(-1)), endrin (<2.3 ng g(-1)) concentrations were
      homogeneous however, HCB (Hexachlorobenzene) and lindane concentrations were
      found undetectable level along the coast. DDE/DDT ratio in the caged mussels form
      Gulluk and Gokova Bay indicated recent DDT (Dikloro difenil trikloroethan) usage
      in these areas. The residues of organochlorinated compounds in transplanted
      mussels confirm the long persistence of DDTs. According to world health
      authorities, the concentration of heavy metals in mussels for the study area can
      generally be considered not to be at levels posing a health risk except Zn. The
      levels of POPs indicated that transplanted mussels have a lack of risk for the
      human health.

PMID- 23972909
TI  - Roles of pyrolysis on availability, species and distribution of Cu and Zn in the
      swine manure: chemical extractions and high-energy synchrotron analyses.
AB  - Animal manures generally contain high levels of heavy metals that may pose a
      significant threat to soil and groundwater qualities. Pyrolysis as means of
      reducing metal availability in such feed stocks is recently encouraged, but
      systematic studies are currently lacking. The aim of this study was to assess the
      impact of pyrolysis temperature on the availability of Cu and Zn by chemical
      extraction, to determine the speciation of Cu and Zn by synchrotron-based X-ray
      spectroscopy, and finally to investigate the phase distribution of metal species
      in the carbonaceous materials by combining acid-base extractions and absorption
      spectroscopy data. The results showed that both Cu and Zn in the swine manure
      were mainly bound to organic functional groups. Cu (II) reduction and Cu (I)-S
      complexes were observed during the pyrolysis process. Zn species resembling ZnAc2
      was still dominant, being 60.8-69.2%, and ZnS increased by 6.6-21.8% in the
      carbonaceous materials. The distribution of Cu and Zn in the mineral, carbonized
      and non-carbonized organic phases varied greatly with the pyrolysis temperature.
      The higher the temperature, the more the metals existed in the mineral phase and
      carbonized organic phase. The decrease of EDTA extractable Cu and Zn with
      pyrolysis temperature was due to the increase of metals in the carbonized organic
      phase and mineral phase. It is suggested that pyrolysis at the relatively higher
      temperature is a better choice for metal-containing manure according to the metal
      speciation, solubility and availability. 

PMID- 23972910
TI  - Relevance study of bare and coated zero valent iron nanoparticles for lindane
      degradation from its by-product monitorization.
AB  - Zero-valent iron nanoparticles (NZVI) as well as polymer-stabilized nanoparticles
      were synthesized and used for lindane (gamma-hexachlorocyclohexane) degradation
      in aqueous solution. To study the effectiveness of the different coated
      nanoparticles, simple and rapid analytical methods have been developed to measure
      and to detect lindane and its by-products. For the monitorization of lindane
      degradation solid-phase extraction (SPE) was used, while volatile by-products
      formation measurement was carried out by headspace-solid phase microextraction
      (HS-SPME) followed by GC/MS. The SPE-GC/MS method provides low detection limits
      (0.2 MUg L(-1)), high recovery (above 95%) and it is a valuable tool for kinetic
      studies of the degradation process for each polymer used, while HS-SPME-GC/MS has
      proved to be an effective tool for the extraction and evaluation of volatile
      degradation by-products.

PMID- 23972911
TI  - Extraosseous talotarsal stabilization.

PMID- 23972912
TI  - Second to fourth digit ratio confirms aggressive tendencies in patients with
      boxers fractures.
AB  - BACKGROUND: Upper limb second to fourth digit ratio (2D:4D) has been shown to be
      dependent on prenatal androgen exposure. A longer relative fourth digit to second
      digit is indicative of increased intrauterine testosterone exposure prenatally
      and the converse is also true for oestrogen exposure. The 2D:4D ratio has
      implications in the sporting, academic, financial and sexual arenas. The purpose
      of this study was to examine the association between smaller finger length ratios
      (2D:4D) and boxers fractures, in both men and women, by comparing the 2D:4D
      ratios in 150 boxers fractures and comparing them to matched controls. Boxers
      fractures are an injury classically incurred during acts of aggression and we
      postulated that this cohort of patients would have a smaller 2D:4D ratio in
      comparison to the normal population mean ratio. METHODS: One hundred and fifty
      radiographs from patients with boxers fractures secondary to aggressive actions
      were analysed and the 2D:4D ratio was calculated. A further 150 X-rays from
      patients not involved in aggressive activities were used as a control group and
      the 2D:4D ratio was calculated in the same manner. We then performed statistical
      analysis to compare the 2D:4D ratios between our two groups. RESULTS: As
      predicted, the 2D:4D in males was smaller than females in all of the groups.
      However, our results showed that those presenting with a boxers fracture due to
      an aggression related injury had a statistically significant smaller 2D:4D ratio
      when compared to the normal population. CONCLUSION: Boxers fractures are injuries
      that typically occur from an aggressive act. It is well documented that a low
      2D:4D ratio is reflective of an increased prenatal exposure to androgens,
      particularly testosterone. We have shown that boxers fractures are associated
      with a smaller 2D:4D ratio than the normal population, thus suggesting that
      persons exposed to high levels of prenatal androgens are more likely to exhibit
      aggressive tendencies in adulthood. Our results suggest that smaller digit ratios
      may predict a predisposition to acts of aggression, and as such result in an
      increased likelihood of sustaining an injury such as a boxers fracture. This
      relationship seems to be present independently of gender.

PMID- 23972913
TI  - Tuberculous meningitis: more questions, still too few answers.
AB  - Tuberculous meningitis is especially common in young children and people with
      untreated HIV infection, and it kills or disables roughly half of everyone
      affected. Childhood disease can be prevented by vaccination and by giving
      prophylactic isoniazid to children exposed to infectious adults, although
      improvements in worldwide tuberculosis control would lead to more effective
      prevention. Diagnosis is difficult because clinical features are non-specific and
      laboratory tests are insensitive, and treatment delay is the strongest risk
      factor for death. Large doses of rifampicin and fluoroquinolones might improve
      outcome, and the beneficial effect of adjunctive corticosteroids on survival
      might be augmented by aspirin and could be predicted by screening for a
      polymorphism in LTA4H, which encodes an enzyme involved in eicosanoid synthesis.
      However, these advances are insufficient in the face of drug-resistant
      tuberculosis and HIV co-infection. Many questions remain about the best
      approaches to prevent, diagnose, and treat tuberculous meningitis, and there are
      still too few answers. 

PMID- 23972914
TI  - Ethical aspects of social freezing.
AB  - The term "social freezing" is used to degrade the reason for freezing eggs to the
      level of a wish instead of a need. The main problem is that the distinction
      between "social" and "medical" freezing is very difficult to make and many
      applications do not fit nicely into one of the categories. The rejection of these
      applications also suffers from a number of inconsistencies. Given the
      difficulties in separating the two models, it is proposed that all applications,
      regardless of the reason, should be evaluated with the same criteria: efficiency,
      safety and justice. 

PMID- 23972915
TI  - [Regulating pre-antral follicle development: a brake on depletion of the ovarian
      reserve].
AB  - The process of folliculogenesis is a complex and dynamic process that is
      regulated by positive and negative factors. During folliculogenesis in the
      mammalian ovary, the primordial follicle pool is gradually reduced through
      successive waves of follicle growth. It is important that this pool is carefully
      regulated, otherwise premature ovarian failure will occur. This process results
      in the ovulation of an ovocyte or more commonly, the loss of ovocytes through
      atresia. The majority of research has concentrated on the positive regulators of
      follicle growth with very little attention on the negative regulators.
      Nonetheless, there are several factors that have been observed to inhibit
      follicle activation and development. In this review, we summarize those here. 

PMID- 23972916
TI  - [Fertility preservation in boys: spermatogonial stem cell transplantation and
      testicular grafting].
AB  - Spermatogonial stem cells (SSC) are the founder cells of spermatogenesis and are
      responsible for the lifelong production of spermatozoa. The cryopreservation and
      transplantation of these cells has been proposed as a fertility preservation
      strategy for young boys at risk for stem cell loss, i.e. patients undergoing
      chemotherapy for cancer or as a conditioning treatment for bone marrow
      transplantation. To prevent lifelong sterility in boys, two fertility restoration
      strategies are being developed: the injection of SSC and the grafting of
      testicular tissue containing SSC. Depending on the disease of the patient one of
      these two approaches will be applicable. Grafting has the advantage that SSC can
      reside within their natural niche, preserving the interactions between germ cells
      and their supporting cells and may therefore be regarded as the first choice
      strategy. However, in cases where the risk for malignant contamination of the
      testicular tissue is real, e.g. leukemia, transplantation of SSC by injection is
      preferable over grafting. 

PMID- 23972917
TI  - [In vitro spermatogenesis... new horizon to restore fertility?].
AB  - The survival of the young boy after cancer has considerably progressed in recent
      years due to the efficiency of chemo/radiotherapy against the tumor cells.
      However, this treatment causes adverse effects on healthy tissues, including
      fertility. Freezing testicular tissue before highly gonadotoxic treatment is a
      prerequisite for preserving fertility in prepubertal boys that do not produce
      sperm yet. But which strategy proposes to restore fertility from frozen-thawed
      testicular tissue? One potential solution would be to consider an in vitro
      maturation of spermatogonial stem cells. In this article we trace the
      chronological development of in vitro spermatogenesis that resulted in mouse
      sperm production in vitro and give an overview of new challenges for the future. 

PMID- 23972918
TI  - [Feasibility, morbidity and survival of surgery combined with HIPEC in the
      management of recurrent ovarian cancer].
AB  - OBJECTIVE: The management of recurrent ovarian cancer is based on intravenous
      chemotherapy with or without debulking surgery. The hyperthermic intraperitoneal
      chemotherapy (HIPEC) is sometimes proposed as a complement to complete surgery.
      The purpose of this study was to evaluate the feasibility, morbidity and survival
      of HIPEC associated with complete surgical cytoreduction in the management of
      patients with a first recurrence of ovarian cancer. PATIENTS AND METHODS: Between
      2005 and 2010, 27 patients underwent surgery for a recurrence of ovarian cancer.
      Among them, 17 patients (63%) have received HIPEC. RESULTS: Sixteen patients
      (94%) were completely resected after surgery. No patient died postoperatively.
      Two patients had intraoperative complications: a bladder injury and a section of
      the ureter. Eight patients had postoperative complications including 3 grade 3 or
      higher (two organ failure and one reoperation). Fifteen patients had a recurrence
      with a median DFS of 11.9 months (95% CI [5.4-32.9]) from the HIPEC. The median
      overall survival from diagnosis was 107.8 months. DISCUSSION AND CONCLUSION:
      These results showed that the association of HIPEC with a complete cytoreduction
      for recurrent ovarian cancer presents acceptable morbidity and survival. The
      results of the ongoing French multicenter study (CHIPOR) are expected to
      generalize this support.

PMID- 23972919
TI  - [2013 vulvodynia update].
AB  - Provoked vestibulodynia represents the most frequent cause of dyspareunia before
      menopause. Vulvodynia's pain and burning sensations are related to neuropathic
      pain and associated to various degrees of vulvar mucosal hypersensitivity (mostly
      in the vestibular area), pelvic floor muscles dysfunction, a disorder of general
      perception of pain and/or various complex regional pain syndromes such as
      fibromyalgia, glossodynia, painful bladder syndrome (interstitial cystitis)...
      Vaginal infections such as candidiasis and vaginosis are important trigger and
      risk factors. Women suffering from vulvodynia are often described as vulnerable,
      pessimistic, developing feelings of guilt towards their partner. They tend to be
      hyper vigilant to their pain and develop catastrophizing reactions (rumination,
      magnification and helplessness) and avoidance/escape behaviors (fear-avoidance
      model). Diagnosis is based on medical history, clinical examination (Q-tip test)
      and exclusion of vaginitis. Treatment consists of a multidisciplinary approach
      involving topical therapies (emollients, anesthetics, hormonotherapy if
      necessary), pelvic floor physiotherapy with electromyographic biofeedback, drug
      treatment of pain with antidepressants (amitriptyline...) or anticonvulsants
      (pregabaline...) and a psychosexual support. 

PMID- 23972920
TI  - [Interest of selective progesterone receptor modulators in endometriosis].
AB  - The SPRM (selective progesterone receptor modulators) are agonists and/or
      antagonists of progesterone receptor. They are responsible for anovulation,
      amenorrhea and a lower prostaglandin levels, which leads to an improvement in
      pain and regression of lesions in endometriosis. On the endometrium, a particular
      aspect, the progesterone receptor modulator-associated endometrial changes
      (PAEC), raises additional studies to verify its harmlessness. However, due to the
      lack of hypoestrogenism and metabolic effects with these drugs, it is very likely
      that the SPRM will in the near future an important place in the treatment of
      endometriosis. 

PMID- 23972921
TI  - [The postnatal contraception: upon 600 patients of whom 129 were postnatal
      controlled].
AB  - OBJECTIVE: To draw a parallel between the contraceptive methods prescribed in the
      post-natal ward and the contraceptive methods taken by patients during their
      postnatal visit. PATIENTS AND METHODS: This piece of work draws information from
      a prospective 10 weeks study at a University Teaching Hospital post-natal ward on
      the contraception that is prescribed upon leaving the maternity ward and also at
      the time of the post-natal visit. RESULTS: From the 600 cases studied, the
      analysis is about 129 patients reviewed in the post-natal visit. The percentage
      of loss was 78.5%. A hormonal contraceptive pill was prescribed to 73.5% of women
      (441 patients) after birth in which 63.5% had microprogestative pills. At the
      earliest, the IUD was given at about 5.4 weeks postpartum. At the time of the
      postnatal visit, compliance was bad for one third of women with either estrogen
      plus progestin methods, microprogestative or natural methods. Women who chose a
      barrier method were only 45.5% to follow this choice, the others left without
      contraception. DISCUSSION AND CONCLUSION: The prescription of postpartum
      contraception was followed by only 66.6% of women. In order to prescribe a more
      effective contraceptive method, we must improve the prescriber's timing in
      sharing contraceptive information and completeness of the contraceptive methods
      offered.

PMID- 23972923
TI  - [Social egg freezing: which problems?].
AB  - In today's society, many women push pregnancy further away from the "right"
      childbearing age. Assisted reproduction, except egg donation, is unable to fully
      overcome the effect of age on fertility loss. The effectiveness of oocyte
      vitrification is demonstrated, and oocyte vitrification is allowed in the French
      Bioethics law of 2011. In the French law, oocyte' s cryopreservation is proposed
      to oocyte donors without child. Social egg freezing for non-medical reason is
      already legal in some countries, but leads to new debates and discussions. 

PMID- 23972922
TI  - [PROK1, prognostic marker of embryo implantation?].
AB  - In spite of improvements in assisted reproductive technology (ART) during the
      last 30 years, the rate of pregnancy remains constrained, as only about 25 % of
      embryo transfer lead to successful pregnancies, even with an average of two
      embryos replaced. Embryo selection is currently based on the establishment of
      morphokinetic scores, a method that obviously exhibits limitations. Therefore,
      the assessment of embryo development potency by criteria of higher predictive
      value is mandatory in order to increase the rates of pregnancy. Nowadays, there
      is increasing evidence that angiogenic factors might contribute to the success of
      the implantation and to the pregnancy outcome. Among these factors, prokineticin
      1 (PROK1) and its receptors (PROKRs) constitute new targets that showed over the
      last ten years strong biological features directly linked to ovarian physiology,
      endometrial receptivity, embryo implantation and thus successful pregnancies. In
      ART, the rates of circulating PROK1 were reported in 2012 as significantly linked
      to the quality of embryonic cohort, as well as to the rates of pregnancy. Our
      preliminary data suggest a high potential of this cytokine in the success of
      implantation and pregnancy, and strongly overtones the emergency to investigate
      the value of its measurement in conditioned media of oocytes and embryo cultures
      in ART.

PMID- 23972924
TI  - [Genotoxicity risk assessment and oocytes: basis of genetic toxicology and
      application in reproductive science].
AB  - The aim of genotoxicity tests in germ cells is to assess the impact of exposure
      to environmental mutagens that may represent a risk for the fertility or for the
      offspring of exposed subject. The comet assay on mature mouse oocytes is a
      simple, reproductive and rapid test to study primary DNA damage in oocytes. This
      test is used to complete toxicology assays applied in first line to somatic
      cells, and could find many applications in reproductive toxicology to study
      impact of environmental factors on female germ cells. We describe a practical
      application of comet assay in reproductive biology to assess the genotoxicity of
      cryoprotectants used at high concentrations in oocyte vitrification protocols.
      This test allowed us to demonstrate that dimethylsulfoxide and ethylene glycol
      are non-genotoxic for the mouse oocytes and led us to hypothesize a genotoxic
      effect of 1,2-propanediol (PrOH) at high concentrations after having observed
      induction of significant DNA damage on CHO cell line and on mouse oocytes. 

PMID- 23972925
TI  - [GnRH agonist triggering in IVF and luteal phase support in women at risk of
      ovarian hyperstimulation syndrome].
AB  - OBJECTIVE: To evaluate the efficacy and safety of ovulation triggering by
      agonists in antagonists IVF cycles with fresh embryo transfer in modulating low
      HCG dose for luteal phase support in patients at risk of ovarian hyperstimulation
      syndrome (OHSS). PATIENTS AND METHODS: In an observational study from September
      2011 to March 2013, we triggered with agonist 107 cycles with OHSS risk, we
      initially triggered 39 cycles with 2 doses of Triptorelin 0.1 mg. Injection of
      1500 IU HCG was performed one hour after the pick up and a second injection of
      1500 IU was made 5 days later (group 1) combined with 400 mg of natural
      progesterone vaginally. In the following 68 cycles we removed the second HCG
      injection and increased to 600 mg vaginal progesterone associated with E2 4 mg
      orally (group 2). RESULTS: Group 1: the ongoing pregnancy rate and birth rate in
      fresh cycle is respectively 37.1% and 34.3% and the cumulative ongoing pregnancy
      rate and birth rate per patient is 43.6% and 41%. We recorded three late onset
      OHSS in pregnant women. Group 2: ongoing pregnancy rate in fresh cycle is 39.6%,
      the current cumulative ongoing pregnancy rate per patient was 45.6%. We observed
      a case of early onset OHSS. DISCUSSION AND CONCLUSION: Triggering with agonist
      and administering an injection of 1500 IU of HCG the day of the pick up appears
      to be effective in women at risk of OHSS. The exclusion of all OHSS is still not
      reached. The search for the best protocol and its indications should continue.

PMID- 23972926
TI  - Season, temperature and blood pressure: a complex interaction.
AB  - An increase in blood pressure values measured during winter either in the office,
      at home, or at ambulatory blood pressure monitoring was consistently observed.
      Besides potentially contributing to increase the risk for cardiovascular events
      during the cold season, long term blood pressure variations can influence results
      of clinical trials, epidemiological surveys, and require personalized management
      of antihypertensive medications in the single patient. Those variations are often
      considered as an effect of climate, due to the close correlation observed in
      various countries and in different settings between temperature and blood
      pressure among children, adults, and specially the elderly. However, obtaining
      true measurements of exposition is a main problem when investigating the effects
      of climate on human health especially when the aim is to disentangle the effects
      of climate from those of seasonality. The aim of the present note is not to
      provide a complete review of the literature demonstrating the implications of
      seasonal blood pressure changes in the clinical and experimental setting; rather
      it is to consider methodological aspects useful to investigate the interaction
      between seasonality and temperature on blood pressure and to make health care
      providers aware of the implications of environmental factors on blood pressure in
      clinical and research settings. 

PMID- 23972927
TI  - A golden approach to ion channel inhibition.
AB  - Drugs are often used in combination and, for pharmacologists, the manner of their
      interactions can cast light on drug mechanisms and biological processes. Here we
      provide simplified descriptions of commonly used analytical methods for analysing
      drug combinations and describe a new and practical experimental solution to
      address the mechanistic question: 'Do two channel-blocking drugs bind at the same
      site?' We define two simple mathematical models that describe the effects of two
      channel blockers acting simultaneously at either the same (Syntopic Model) or
      different (Allotopic Model) binding sites within a channel pore. We find that the
      optimum concentrations of two drugs for distinguishing between the two models are
      related to the mathematical Golden Ratio. 

PMID- 23972928
TI  - Persisting pain after endovascular treatment of a symptomatic aortic aneurysm.
AB  - INTRODUCTION: Usually patients are admitted to hospital with a single diagnosis,
      but if complaints persist it is important to consider a synchronous secondary
      diagnosis. PRESENTATION OF CASE: A 74-year-old woman presented with severe
      abdominal and back pain. On physical examination, a tender abdominal aortic
      aneurysm (AAA) was noted. Following endovascular treatment of the AAA, pain in
      the right lower abdomen persisted. Review of the pre-EVAR CT images revealed a
      foreign body in the terminal ileum, which was surgically removed. DISCUSSION:
      Patients with foreign-body-related intestinal pain present with complaints of
      abdominal pain at initial presentation. The accompanied back pain and abdominal
      tenderness of the abdominal aorta in our case could indicate another diagnosis.
      CONCLUSION: Persisting complaints post-intervention should not only arouse
      suspicion of an intervention-related complication, but also of a synchronous
      second diagnosis.

PMID- 23972929
TI  - Risk of not being discharged home after isolated coronary artery bypass graft
      operations.
AB  - BACKGROUND: The age and risk profile of patients undergoing isolated coronary
      artery bypass grafting (CABG) is increasing, which will likely increase the
      proportion of CABG patients discharged to nursing homes, rehabilitation, or long
      term care. Because discharge disposition can be important to a patient's
      treatment goals, developing and using predictive tools will improve informed
      treatment decision making. We examined the utility of The Society of Thoracic
      Surgeons (STS) risk of mortality score in predicting discharge disposition after
      CABG. METHODS: From January 1, 2004 to October 31, 2011, 5,119 patients underwent
      isolated CABG at The Heart Hospital Baylor Plano or Baylor University Medical
      Center (Texas) and were discharged alive. The association between STS risk of
      mortality and discharge to nursing home, rehabilitation, or long-term care was
      assessed using multivariable logistic regression, adjusted for age, body surface
      area, marital status, site, and year of operation. RESULTS: At discharge, 216
      patients (4.21%) went to nursing homes, 153 (2.99%) to rehabilitation, and 115
      (2.25%) to long-term care. The STS risk of mortality score was significantly
      positively associated with discharge status (p < 0.001). Patients with 1%, 2%,
      3%, 4%, and 5% STS risk of mortality had 11.25%, 22.10%, 29.45%, 35.00%, and
      38.50% probability, respectively, of not being discharged home. When the STS risk
      of mortality was 5%, the risk of not being discharged home was 47.9% for off-pump
      patients and 38.10% for on-pump patients. CONCLUSIONS: STS risk score is strongly
      associated with CABG discharge status. Patients with a risk score exceeding 2 are
      at high risk (>22%) of not being discharged home. This risk should be discussed
      when treatment decisions are being made.

PMID- 23972930
TI  - The efficacy of EBUS-guided transbronchial needle aspiration for molecular
      testing in lung adenocarcinoma.
AB  - BACKGROUND: The purpose of the study was to assess the efficacy of obtaining
      adequate cytologic specimens by endobronchial ultrasound-guided transbronchial
      needle aspiration (EBUS-TBNA) for molecular testing of lung adenocarcinomas.
      METHODS: This was an institutional review board-approved study of all patients
      who had undergone EBUS-TBNA from April 2010 through March 2012 for the diagnosis,
      staging, or both of lung cancer. Patients with a diagnosis of adenocarcinoma were
      reflexively tested for molecular markers by polymerase chain reaction,
      sequencing, and fluorescence in situ hybridization (FISH). All procedures were
      performed with patients under conscious sedation in the bronchoscopy suite.
      RESULTS: Of 205 patients who underwent EBUS-TBNA, 56 patients (24 male, 32
      female) had a diagnosis of adenocarcinoma warranting molecular analysis.
      Molecular analysis was available for epidermal growth factor receptor (EGFR),
      Kirsten rat sarcoma (Kras) mutation, and anaplastic lymphoma kinase (ALK) gene
      rearrangement. The institution's clinical protocol involved initial testing for
      EGFR mutation with a reflex Kras test if the EGFR test result was negative. ALK
      FISH molecular testing was completed if both EGFR and Kras test results were
      negative. A total of 52 of 56 (93%) patients had sufficient cytologic material
      for complete or partial molecular testing, whereas 46 of 56 (82%) patients had
      sufficient material for all clinically indicated testing. EGFR, Kras, and ALK
      analysis yielded positive results in 5 (10%), 10 (25%), and 5 (12%) tested
      specimens, respectively. No complications were associated with EBUS-TBNA.
      CONCLUSIONS: EBUS-TBNA performed with the patient under moderate sedation can be
      expected to yield sufficient tissue for sequential molecular analysis in the
      majority of patients. In an era of targeted therapy for lung adenocarcinomas,
      EBUS-TBNA is effective in clinical practice for complete diagnosis, staging, and
      treatment planning in these patients.

PMID- 23972931
TI  - Use of transaortic, transapical, and transcarotid transcatheter aortic valve
      replacement in inoperable patients.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an effective
      treatment in patients with severe aortic stenosis unsuitable for surgical aortic
      valve replacement (SAVR). This study evaluated the early experience with the
      posttrial application of TAVR, with specific focus on non-transfemoral (TF)
      access. METHODS: All patients who underwent posttrial TAVR at Emory University
      from November 2011 to April 2012 were reviewed. During this time, 44 posttrial
      TAVRs were performed: TF in 18, transapical in 11, transaortic in 12, and
      transcarotid in 3. RESULTS: A total of 40.9% of all patients were candidates for
      TF implantation. Mean age was 78.2 +/- 11.3 years, and 34.1% were women. Mean
      ejection fraction was 0.463 +/- 0.164, and 90.2% had New York Heart Association
      class III to IV heart failure. Fifty percent were diabetic, 27.3% had moderate to
      severe chronic obstructive pulmonary disease, and 20.5% had a prior stroke. The
      mean creatinine was 1.63 +/- 1.74 mg/dL, 9.1% required preoperative dialysis, and
      61.4% had undergone prior cardiac operations. No patients had postoperative
      myocardial infarction, stroke, or required new dialysis. Intraoperative vascular
      complications occurred in 11.4%. No patient had more than mild perivalvular leak
      by transthoracic echocardiography at discharge. Mean postoperative ventilator
      time was 17.8 +/- 40.1 hours. Intensive care unit length of stay was 58.0 +/-
      67.0 hours. Postoperative hospital length of stay was 6.1 +/- 4.7 days. The 30
      day mortality was 6.8% (3 of 44) for all patients, despite a mean The Society of
      Thoracic Surgeons Predicted Risk of Mortality score of 12.6. CONCLUSIONS: Less
      than half of patients deemed appropriate for posttrial TAVR were candidates for
      TF implantation. The use of all available access routes leads to excellent
      outcomes in patients deemed inoperable.

PMID- 23972932
TI  - A contemporary cost analysis of postoperative morbidity after coronary artery
      bypass grafting with and without concomitant aortic valve replacement to improve
      patient quality and cost-effective care.
AB  - BACKGROUND: The financial burden of postoperative morbidity after cardiac
      operations remains ill defined. This study evaluated the costs associated with
      the performance of coronary artery bypass grafting (CABG) with and without aortic
      valve replacement (AVR) and determined the incremental costs associated with
      major postoperative complications. METHODS: A total of 65,534 regional patients
      undergoing CABG (n = 55,167) +/- AVR (n = 10,367) were evaluated from 2001 to
      2011. Patient-related, hospital-related, and procedure-related cost data were
      analyzed by use of Medicare-based cost reports. Hierarchical multivariable
      regression modeling was used to estimate risk-adjusted incremental cost
      differences in postoperative complications. RESULTS: The mean age was 64 years,
      and women accounted for 31% of patients. CABG + AVR patients had higher rates of
      overall complication (40% vs 35%, p < 0.001) and operative mortality (5% vs 3%, p
      < 0.001) than did CABG patients. CABG + AVR patients also accrued increased
      median postoperative lengths of stay (7 vs 5 days, p < 0.001) and total costs
      ($26,527 vs $24,475, p < 0.001). After mortality risk adjustment, significant
      positive relationships existed between total costs and major postoperative
      complications. Interestingly, the highest incremental costs among CABG patients
      included newly instituted hemodialysis ($71,833), deep sternal wound infection
      ($56,003), and pneumonia ($50,025). Among CABG + AVR patients, these
      complications along with perioperative myocardial infarction ($68,917) dominated
      costs. CONCLUSIONS: Postoperative complications after CABG +/- AVR are associated
      with significantly increased incremental costs. The most costly complications
      include newly instituted hemodialysis, infectious complications, and
      perioperative myocardial infarction. Identification of the most common and the
      most costly complications provides opportunities to target improvement in patient
      quality and the delivery of cost-effective care.

PMID- 23972933
TI  - Outcomes of heart transplantation in small children bridged with ventricular
      assist devices.
AB  - BACKGROUND: Ventricular assist devices (VADs) have been used with increasing
      frequency to bridge small children to heart transplantation (HTx), but outcomes
      in large cohorts are not well established. METHODS: Small children (<= 10 kg)
      bridged to HTx with VADs between 2004 and 2010 were identified in the United
      Network for Organ Sharing database. Survival was modeled using the Kaplan-Meier
      method, and 2:1 propensity matching was used to compare outcomes with a well
      matched control cohort of nonbridged HTx recipients. RESULTS: Of the 803 small
      children who underwent HTx during the study period, 59 (7%) were bridged with a
      VAD. The proportion of recipients that were bridged with a VAD increased from 3%
      in 2004 to 9% in 2010 (p = 0.03). Kaplan-Meier 30-day, 6-month, and 1-year
      survival was comparable between those bridged with a VAD and 118 well-matched
      nonbridged children. Rates of postoperative renal failure, reoperation,
      infection, and rejection were also comparable. Those bridged with a VAD had a
      significantly higher rate of postoperative stroke (8.5% vs 0.9%; p = 0.008).
      CONCLUSIONS: Small children bridged to HTx with a VAD have early survival rates
      that are comparable to nonbridged children; however, this is achieved at the
      expense of a higher rate of stroke. Identifying the risk factors for early death
      and stroke in small children bridged to HTx with VADs is prudent as more
      experience with this patient population accumulates.

PMID- 23972934
TI  - Reentrant and focal activations during atrial fibrillation in patients with
      atrial septal defect.
AB  - BACKGROUND: Adult patients with atrial septal defect frequently experience atrial
      fibrillation. However, the electrophysiologic mechanism has not been directly
      examined, and the optimal surgical procedure has not been determined. METHODS:
      Ten patients undergoing operations for atrial septal defect and atrial
      fibrillation underwent intraoperative mapping by use of 253 epicardial
      electrodes. There were 7 men and 3 women, whose average age was 54 +/- 11 years.
      Eight patients had a secundum defect and 2 a primum defect. There were 4 patients
      with paroxysmal atrial fibrillation and 6 with long-standing persistent atrial
      fibrillation. A modified biatrial Maze procedure was performed in 6 patients and
      pulmonary vein isolation with no other left atrial lesions in 4. RESULTS: The
      reentrant or focal activations driving atrial fibrillation were confined within
      the right atrium in all patients with paroxysmal atrial fibrillation, whereas
      multiple focal activations arising from the pulmonary veins or posterior left
      atrium and reentrant activations in the left atrium were observed in 5 of 6
      patients with long-standing persistent atrial fibrillation. In 9 patients, sinus
      rhythm was restored postoperatively and 8 of those patients have been free of any
      atrial fibrillation during a follow-up period of 94 +/- 45 months. CONCLUSIONS:
      The pattern of the atrial activation during atrial fibrillation correlated with
      the type of atrial fibrillation and varied from a simple right atrial reentry to
      complex reentrant and focal activations in the left atrium.

PMID- 23972936
TI  - Foreword.

PMID- 23972937
TI  - Natural history of mild and of moderate aortic stenosis-new insights from a large
      prospective European study.
AB  - Increased life expectancy has led to a higher prevalence of calcific aortic valve
      disease. Both ends of the disease spectrum-sclerosis of the aortic valve without
      hemodynamic obstruction and the late stage of aortic valve stenosis (AS)-have
      been associated with increased morbidity and mortality. This raises the question
      of the prognostic contribution of atherosclerotic diseases and other
      comorbidities as opposed to the hemodynamic effect of obstructive AS. Hence, the
      evaluation of asymptomatic patients with mild or moderate AS without
      comorbidities is of major interest. In the Simvastatin and Ezetimibe in Aortic
      Stenosis study, with the exception of hypertension, comorbidities were excluded,
      thus allowing an analysis of the effect of pure AS as well as the effect of
      hypertension on the progression and outcome of AS. We discuss the results that
      emerged from this large European prospective study and relate these to the
      published literature. 

PMID- 23972938
TI  - FabQ, a dual-function dehydratase/isomerase, circumvents the last step of the
      classical fatty acid synthesis cycle.
AB  - In the classical anaerobic pathway of unsaturated fatty acid biosynthesis, that
      of Escherichia coli, the double bond is introduced into the growing acyl chain by
      the FabA dehydratase/isomerase. Another dehydratase, FabZ, functions in the chain
      elongation cycle. In contrast, Aerococcus viridans has only a single FabA/FabZ
      homolog we designate FabQ. FabQ can not only replace the function of E. coli FabZ
      in vivo, but it also catalyzes the isomerization required for unsaturated fatty
      acid biosynthesis. Most strikingly, FabQ in combination with E. coli FabB imparts
      the surprising ability to bypass reduction of the trans-2-acyl-ACP intermediates
      of classical fatty acid synthesis. FabQ allows elongation by progressive
      isomerization reactions to form the polyunsaturated fatty acid, 3-hydroxy-cis-5,
      7-hexadecadienoic acid, both in vitro and in vivo. FabQ therefore provides a
      potential pathway for bacterial synthesis of polyunsaturated fatty acids. 

PMID- 23972940
TI  - Chemical activators of protein phosphatase-1 induce calcium release inside intact
      cells.
AB  - Protein phosphatase-1 (PP1) is a major Ser/Thr phosphatase that is involved in
      numerous cellular processes. PP1-disrupting peptides (PDPs) are selective
      chemical tools used to study PP1. They generate catalytically active PP1 inside
      cells but do not bind to the closely related PP2A. Here, we show that PDPs also
      do not act directly on PP2B, thus demonstrating the selectivity of PDPs toward
      PP1. We present PDPs with different properties, enabling reversible versus
      permanent activation of PP1. We also show that Ca(2+) spiking is an acute effect
      caused by PDP-induced activation of PP1. The Ca(2+) is released from internal
      stores. Our data show that PDPs can be used as selective chemical genetics tools
      to study acute and long-term effects of PP1 activation in intact cells, and PDPs
      will therefore be valuable tools to study PP1 biology. 

PMID- 23972939
TI  - Collapsing the proton motive force to identify synergistic combinations against
      Staphylococcus aureus.
AB  - Pathways of bacterial energy metabolism, such as the proton motive force (PMF),
      have largely remained unexplored as drug targets, owing to toxicity concerns.
      Here, we elaborate on a methodical and systematic approach for targeting the PMF
      using chemical combinations. We began with a high-throughput screen to identify
      molecules that selectively dissipate either component of the PMF, DeltaPsi or
      DeltapH, in Staphylococcus aureus. We uncovered six perturbants of PMF, three
      that countered DeltaPsi and three that selectively dissipated DeltapH.
      Combinations of dissipators of DeltaPsi with dissipators of DeltapH were highly
      synergistic against methicillin-resistant S. aureus. Cytotoxicity analyses on
      mammalian cells revealed that the dose-sparing effect of the observed synergies
      could significantly reduce toxicity. The discovery and combination of modulators
      of DeltaPsi and DeltapH may represent a promising strategy for combating
      microbial pathogens. 

PMID- 23972941
TI  - Neurocognitive functioning in antiretroviral therapy-naive youth with
      behaviorally acquired human immunodeficiency virus.
AB  - PURPOSE: Youth living with human immunodeficiency virus (HIV) account for over
      one third of new HIV infections and are at high risk of adverse psychosocial,
      everyday living, and health outcomes. Human immunodeficiency virus-associated
      neurocognitive disorders (HAND) are known to affect health outcomes of HIV
      infected adults even in the era of combination antiretroviral therapy. Thus, the
      current study aimed to characterize the prevalence and clinical correlates of
      HAND in youth living with HIV. Here, we report baseline neurocognitive data for
      behaviorally HIV-infected youth enrolled in a prospective study evaluating
      strategies of antiretroviral treatment initiation and use. METHODS: A total of
      220 participants, age 18-24 years, who were naive to treatment (except for
      prevention of mother-to-child HIV transmission; n = 3), completed a comprehensive
      neurocognitive, substance use, and behavioral health assessment battery. RESULTS:
      Sixty-seven percent of youth met criteria for HAND (96.4% were asymptomatic and
      3.5% were syndromic); deficits in episodic memory and fine-motor skills emerged
      as the most commonly affected ability areas. Multivariable models showed that
      lower CD4 count, longer time since HIV diagnosis, and high-risk alcohol use were
      uniquely associated with neurocognitive deficits. CONCLUSIONS: Over two thirds of
      youth with behaviorally acquired HIV evidence neurocognitive deficits, which have
      modest associations with more advanced HIV disease as well as other factors.
      Research is needed to determine the impact of such neuropsychiatric morbidity on
      mental health and HIV disease treatment outcomes (e.g., nonadherence) and
      transition to independent living responsibilities in HIV-infected youth, as well
      as its long-term trajectory and possible responsiveness to cognitive
      rehabilitation and pharmacotherapy.

PMID- 23972942
TI  - Cortisol and testosterone in hair as biological markers of systolic heart
      failure.
AB  - BACKGROUND: Congestive heart failure (CHF) is associated with increased stress
      and alterations in metabolism, favoring catabolism over anabolism. Hormonal
      profiles of patients with heart failure have been assessed using serum and saliva
      as matrices, which are only point measurements and do not provide long-term
      information. Scalp hair is a novel matrix that allows for measurement of hormones
      over a period of several months. PATIENTS AND METHODS: We aimed to evaluate
      whether levels of cortisol and testosterone and their ratio (C/T) in hair
      correlate with severity of heart failure. We conducted a prospective study in
      ambulatory male patients with a left ventricular ejection fraction (LVEF)<=40%.
      Hormone levels were measured using immunoassays in the proximal 2 cm of hair
      (representing approximately two months of systemic hormone exposure). Primary
      endpoints included the correlation of hair cortisol, testosterone, and C/T levels
      with the New York Heart Association (NYHA) class, LVEF, exercise capacity and NT
      proBNP. RESULTS: The 44 CHF patients had a median hair level (range) of cortisol
      of 207 (117.7-1277.3)ng/g. Hair cortisol levels correlated positively with NYHA
      class (r=0.48, p=0.001) and negatively with treadmill stress test performance,
      (r=-0.37, p<0.05). The hair testosterone was 5.17 (2.39-24.64)ng/g and the C/T
      ratio was 39.89 (12.98-173.73). No associations were found between hair
      testosterone and C/T ratio and heart failure severity; however, the C/T ratio was
      higher in patients who required a CHF-related hospitalization than in patients
      who did not require this in the year following the inclusion in the study.
      CONCLUSIONS: Hair cortisol levels correlate with heart failure severity as
      assessed by the NYHA class and exercise capacity, while hair testosterone and C/T
      levels do not correlate with heart failure severity.

PMID- 23972943
TI  - The impact of social exclusion vs. inclusion on subjective and hormonal reactions
      in females and males.
AB  - BACKGROUND: The experience of social exclusion represents an extremely aversive
      and threatening situation in daily life. The present study examined the impact of
      social exclusion compared to inclusion on steroid hormone concentrations as well
      as on subjective affect ratings. METHODS: Eighty subjects (40 females)
      participated in two independent behavioral experiments. They engaged in a
      computerized ball tossing game in which they ostensibly played with two other
      players who deliberately excluded or included them, respectively. Hormone samples
      as well as mood ratings were taken before and after the game. RESULTS: Social
      exclusion led to a decrease in positive mood ratings and increased anger ratings.
      In contrast, social inclusion did not affect positive mood ratings, but decreased
      sadness ratings. Both conditions did not affect cortisol levels. Testosterone
      significantly decreased after being excluded in both genders, and increased after
      inclusion, but only in males. Interestingly, progesterone showed an increase
      after both conditions only in females. DISCUSSION: Our results suggest that
      social exclusion does not trigger a classical stress response but gender-specific
      changes in sex hormone levels. The testosterone decrease after being excluded in
      both genders, as well as the increase after inclusion in males can be interpreted
      within the framework of the biosocial status hypothesis. The progesterone
      increase might reflect a generalized affiliative response during social
      interaction in females.

PMID- 23972944
TI  - Adequate endocrine and cardiovascular response to social stress in survivors of
      childhood acute lymphoblastic leukemia.
AB  - Survivors of childhood ALL have been demonstrated to have increased morning
      cortisol levels compared to healthy controls. Information regarding the response
      of the HPA axis and the sympathetic nervous system to stress in childhood ALL
      survivors is not available. The present study aimed at assessing the endocrine
      and cardiovascular stress response in childhood ALL survivors and healthy
      controls by evaluating perceived stress on visual analog scales, by determining
      saliva cortisol, blood pressure and heart rate in response to the Trier Social
      Stress Test for Children (TSST-C). Fifty survivors who had completed their
      treatment for childhood ALL 57 (IQR 47.0-72.3) months before and 50 healthy age
      and sex matched controls were included. Exposure to the TSST-C induced a
      significant response of perceived stress, saliva cortisol and cardiovascular
      outcome variables in the total study group. These responses did not significantly
      differ between survivors of childhood ALL and healthy controls. We conclude that
      the endocrine and cardiovascular response to social stress are intact in
      survivors of childhood ALL. 

PMID- 23972945
TI  - Wound contraction decreases with intravenously injected substance P in rabbits.
AB  - Substance P is an injury-inducible endogenous factor for the mobilization of
      CD29+ stromal-like cells into circulation and that are major effectors of
      accelerated healing. In this study, we evaluated the effect of intravenously
      injected substance P on full-thickness skin wound healing as a secondary
      intention wound model. We made circular full-thickness skin wounds on the ears of
      28 New Zealand white rabbits. They were treated with phosphate-buffered saline,
      or intravenous 5, 50, or 250 n mole/kg substance P at days 0 and 1. All substance
      P-treated groups showed a 2.6-5.4-fold higher CD29 expression and resulted in
      greatly decreased wound contraction and early maturation of the stroma. However,
      a significant decrease in wound contraction was measured only in the 5 n mole/kg
      treatment group. We conclude that intravenously injected substance P at 5 n
      mole/kg decreases wound contraction and promotes wound maturation in full
      thickness skin wounds in a rabbit ear model.

PMID- 23972947
TI  - High-potency statins and acute kidney injury-associated hospitalizations.

PMID- 23972948
TI  - Research data sharing: Lessons from forensic genetics.

PMID- 23972946
TI  - Evidence for gamma and beta sensory gating deficits as translational
      endophenotypes for schizophrenia.
AB  - Thorough analysis of translational endophenotypes is needed to improve
      therapeutic development in schizophrenia. Abnormal sensory gating, one such
      endophenotype, is associated with reduced expression of the alpha7 nicotinic
      receptor. However, typical gating measures such as the P50 evoked response are
      often low-pass filtered, and it is unclear how alpha7 expression affects gating
      at higher frequencies. Therefore, this study used time-frequency analysis to
      compare sensory gating at the beta and gamma frequencies between human patients
      and healthy controls as well as between alpha7 heterozygote mutant mice and wild
      type. Gating of total beta (15-26Hz) and gamma (30-50Hz) power during paired
      clicks was assessed from mouse in vivo hippocampal CA3 recordings. Gating was
      also assessed in schizophrenia patients and healthy controls using
      electroencephalography. Relative to wild-type, alpha7 heterozygote mice showed
      impaired gating of total beta and gamma power. Similarly, relative to controls,
      patients showed impaired gating of total beta and gamma power. Poor beta gating
      was associated with negative symptoms. These results demonstrate that
      schizophrenia patients and alpha7 heterozygote mice show similar deficits in
      gating high frequency power. Time-frequency analysis of beta and gamma gating may
      thus be a translational method of assessing the genetic basis of gating deficits
      in schizophrenia. 

PMID- 23972949
TI  - Genetic diversity of Haemophilus parasuis from sick and healthy pigs.
AB  - A collection of 94 Haemophilus parasuis isolates was used for this study. It
      consisted of isolates from organs of pigs with Glasser's disease and pneumonia
      (n=54), from nasal swabs of healthy pigs in farms without Glasser's disease
      problems (n=25), and 15 reference strains. These isolates were typed using a new
      multilocus variable number of tandem repeats analysis (MLVA) protocol and
      investigated for the presence of nine putative virulence genes. The new MLVA
      protocol was highly discriminatory (54 types identified and discrimination index
      of 97.4%) and reproducible. Similar to previous investigations done with other
      methods, two major genetic clusters were identified by MLVA, which partially
      correlated with serotype and virulence gene distributions. Gene linkage analysis
      suggested that lateral gene transfer occurs within each of these clusters, but
      rarely between them. Although one single MLVA type included more than 20% of the
      clinical isolates, no significant correlation was detected between a specific
      MLVA type, the major genetic clusters, or the presence of any of the virulence
      genes investigated or the source of the isolates (clinical infection vs. healthy
      pig). The MLVA typing protocol described in this study is a promising new tool
      for future investigations into the epidemiology of Glasser's disease and could
      help us to better understand interacting microbial, host and environmental
      factors that lead to the development of H. parasuis disease. 

PMID- 23972950
TI  - Schmallenberg virus experimental infection of sheep.
AB  - Since late 2011, a novel orthobunyavirus, named Schmallenberg virus (SBV), has
      been implicated in many cases of severely malformed bovine and ovine offspring in
      Europe. In adult cattle, SBV is known to cause a mild transient disease; clinical
      signs include short febrile episodes, decreased milk production and diarrhoea for
      a few days. However, the knowledge about clinical signs and pathogenesis in adult
      sheep is limited. In the present study, adult sheep of European domestic breeds
      were inoculated with SBV either as cell culture grown virus or as virus with no
      history of passage in cell cultures. Various experimental set-ups were used.
      Sampling included blood collection at different time points during the
      experimental period and selected organ material at autopsy. Data from this study
      showed, that the RNAemic period in sheep was as short as reported for cattle;
      viral genome was detectable for about 3-5 days by real-time RT-PCR. In total, 13
      out of 30 inoculated sheep became RNAemic, with the highest viral load in animals
      inoculated with virus from low cell culture passaged or the animal passaged
      material. Contact animals remained negative throughout the study. One RNAemic
      sheep showed diarrhoea for several days, but fever was not recorded in any of the
      animals. Antibodies were first detectable 10-14 days post inoculation. Viral RNA
      was detectable in spleen and lymph nodes up to day 44 post inoculation. In
      conclusion, as described for cattle, SBV-infection in adult sheep predominantly
      results in subclinical infection, transient RNAemia and a specific antibody
      response. Maintenance of viral RNA in the lymphoreticular system is observed for
      an extended period.

PMID- 23972951
TI  - Update on the pathogenesis of Haemophilus parasuis infection and virulence
      factors.
AB  - Haemophilus parasuis is the causative agent of Glasser's disease in pigs, a
      severe systemic disease that has led to increasing economic losses in the pig
      industry worldwide. The H. parasuis genome sequence has been completed, but the
      function and essentiality of the annotated genes remain largely unknown,
      especially virulence factors. The recent developments in the efficient genetic
      manipulation of H. parasuis have greatly facilitated the study of gene function,
      pathogenesis mechanisms and virulence factors. In this review, we provided update
      information regarding that (i) how the pathogen overcome host immune responses
      and cell barriers which were tightly associated with the pathogenesis, and (ii)
      the several recent identification of virulence factors were involved in evading
      the immune responses and cell barriers in H. parasuis. 

PMID- 23972952
TI  - Lipid biomarkers and metabolic effects of lycopene from tomato juice on liver of
      rats with induced hepatic steatosis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver
      disorders, covering steatosis to nonalcoholic steatohepatitis (NASH). Dietary
      factors may modulate its evolution, and antioxidants have been proposed as
      therapeutic agents. Among them, lycopene has been demonstrated to prevent the
      development of steatohepatitis and even to inhibit NASH-promoted early
      hepatocarcinogenesis induced by a high-fat diet in rats. These conclusions have
      been related to its antioxidant activity; however, NAFLD is more complex than a
      simple redox imbalance state since it disturbs several metabolic systems in the
      liver. In consequence, there is a lack of information related to the action of
      lycopene beyond antioxidant biomarkers. In this work, NAFLD was induced in rats
      using a hypercholesterolemic and high-fat diet to evaluate the effect of lycopene
      consumption from tomato juice on liver metabolism. Several classical antioxidant
      biomarkers related to NAFLD were measured to check the state of this disease
      after 7 weeks of the controlled diet. Moreover, a metabolomics platform was
      applied to measure more than 70 metabolites. Results showed clear differences in
      the classical antioxidant biomarkers as well as in the metabolic pattern,
      attending not only to the diet but also to the intake of lycopene from tomato
      juice. Interestingly, tomato juice administration partially reverted the
      metabolic pattern from a high-fat diet to a normal diet even in metabolites not
      related to the redox state, which could lead to new targets for therapeutic
      agents against NAFLD and to achieving a better understanding of the role of
      lycopene in liver metabolism. 

PMID- 23972953
TI  - Combined effect of obesity and cardio-metabolic abnormality on the risk of
      cardiovascular disease: a meta-analysis of prospective cohort studies.
AB  - BACKGROUND: Cardiovascular risk is inconsistent in the normal-weight, overweight,
      and obese individuals due to metabolic abnormality. We aimed to investigate
      combined effects of obesity and metabolic abnormality on the risk of
      cardiovascular disease and mortality. METHODS: The MEDLINE, EMBASE, Cochrane
      library, and references of relevant original articles prior to May 2013 were
      searched for prospective studies investigating cardiovascular risk and death
      associated with combined effects of obesity and metabolic syndrome or insulin
      resistance. Pooled relative risks (RR) and 95% confidence intervals (CI) were
      calculated using random-effects or fixed-effect models when appropriate. RESULTS:
      Fourteen perspective studies with a total of 299,059 participants and 12,125
      cases of incident CVD, 2130 cases of CVD death, and 7071 cases of all-cause death
      were included in the meta-analysis. Compared with healthy normal-weight
      individuals, metabolically healthy overweight (MHOW) and obese (MHOB) individuals
      showed increased risk for CVD events, which appeared much stronger during the
      long-term follow-up period of >15 years, with pooled RR of 1.47 (95% CI 1.37
      1.58) in MHOW and 2.00 (95% CI 1.79-2.24) in MHOB. Normal-weight but
      metabolically abnormal individuals were at increased risk for CVD (pooled RR
      1.81, 95% CI 1.56-2.10), CVD-related death (pooled RR 1.55, 95% CI 1.16-2.08),
      and all-cause death (pooled RR 1.27, 95% CI 1.10-1.47). Metabolically abnormal
      obese individuals were at the highest risk for CVD and mortality. CONCLUSION:
      Individuals with metabolic abnormality, although at normal-weight, had an
      increased risk of CVD and mortality. Healthy overweight and obese persons had
      higher risk, which refuted the notion that metabolically healthy obese phenotype
      is a benign condition.

PMID- 23972954
TI  - Intercellular adhesion molecule 1 (ICAM-1)--a new substrate for the development
      of ventricular fibrillation?

PMID- 23972955
TI  - Effective implementation of time-frequency matched filter with adapted pre and
      postprocessing for data-dependent detection of newborn seizures.
AB  - Neonatal EEG seizures often manifest as nonstationary and multicomponent signals,
      necessitating analysis in the time-frequency (TF) domain. This paper presents a
      novel neonatal seizure detector based on effective implementation of the TF
      matched filter. In the detection process, the TF signatures of EEG seizure are
      extracted to construct the TF templates used by the matched filter. Matching
      pursuit (MP) decomposition and narrowband filtering are proposed for the
      reduction of artifacts prior to seizure detection. Geometrical correlation is
      used to consolidate the multichannel detections and to reduce the number of false
      detections due to remnant artifacts. A data-dependent threshold is defined for
      the classification of EEG. Using 30 newborn EEG records with seizures, the
      classification process yielded an overall detection accuracy of 92.4% with good
      detection rate (GDR) of 84.8% and false detection rate of 0.36FD/h. Better
      detection performance (accuracy >95%) was recorded for relatively long EEG
      records with short seizure events. 

PMID- 23972956
TI  - Scientific publications in obstetrics and gynecology journals from China, 2000
      2009.
AB  - OBJECTIVE: To analyze the output of scientific publications in obstetrics and
      gynecology journals from 3 principal regions of China: mainland China, Taiwan,
      and Hong Kong. METHODS: Information on article numbers, impact factors, citation
      reports, and publication in high-impact obstetrics and gynecology journals by
      Chinese authors between January 1, 2000, and December 31, 2009, was extracted
      from PubMed and WoS databases. Comparisons of quantity and quality were done by
      Kruskal-Wallis and rank-sum tests. RESULTS: There were 3044 articles from
      mainland China (n=1042), Taiwan (n=1304), and Hong Kong (n=698). The cumulative
      impact factors and citations of articles from Taiwan were highest among the 3
      regions. In terms of average impact factor and number of citations per article,
      Hong Kong exceeded mainland China and Taiwan. Fertility and Sterility, Human
      Reproduction and Gynecologic Oncology were among the most popular obstetrics and
      gynecology journals used by authors in the 3 regions. CONCLUSION: The annual
      number of articles published in obstetrics and gynecology journals from the 3
      regions of China increased during the past decade, especially for mainland China.
      However, the quality of articles from mainland China arouses attention because
      the average citation of articles from Hong Kong and Taiwan was higher than that
      of articles from the mainland.

PMID- 23972957
TI  - Early surgical repair of iatrogenic ureterovaginal fistula secondary to
      gynecologic surgery.
AB  - OBJECTIVE: To describe the early surgical repair of iatrogenic ureterovaginal
      fistula (UVF) secondary to gynecologic surgery, and evaluate the efficacy and
      feasibility of early surgical intervention. METHODS: Data were retrospectively
      reviewed for 52 patients with iatrogenic UVF who underwent early surgical repair
      between January 1996 and January 2011 at the Sir Run Run Shaw Hospital, Hangzhou,
      China. Preoperative patient characteristics and postoperative endpoints,
      including type of index procedure, repair technique, operative time,
      perioperative complications, and postoperative follow-up data were assessed.
      RESULTS: All early surgical repairs were uneventful. The mean time from diagnosis
      to surgery was 15.7days (range, 14-21days). The mean operative time was 73.4min
      (range, 51-110min) for ureteroneocystostomy, and 104min (range, 91.5-153min) for
      Boari flap procedure. The mean estimated blood loss was 57.8mL (range, 35-80mL).
      No major intraoperative complications occurred, although 5 patients had
      postoperative surgical site infections. Forty-three patients were followed for a
      mean of 18.4months (range, 10.5-24.0months). Ureteral stricture with asymptomatic
      hydronephrosis occurred in 2 (4.7%) patients. Ipsilateral renal function was
      preserved in all patients. CONCLUSION: Early surgical repair of UVF secondary to
      gynecologic surgery was safe and effective, and preserved ipsilateral renal
      function.

PMID- 23972958
TI  - Clinical aspects and management of cutaneous leishmaniasis in rheumatoid patients
      treated with TNF-alpha antagonists.
AB  - Patients under immunosuppressive therapy with tumor necrosis factor alpha (TNF
      alpha) antagonists are vulnerable to various opportunistic infections including
      leishmaniasis. We present a case series of 8 travellers developing cutaneous
      leishmaniasis whilst on TNF-alpha antagonist treatment and review the literature
      on aspects of cutaneous leishmaniasis developing in patients treated with TNF
      alpha antagonists. We make interim recommendations regarding the drug therapy
      used to maintain remission in travellers with rheumatoid disease travelling to
      leishmania prone areas. Despite having a medical condition requiring continued
      rheumatological review the interval to diagnosis appears not to be reduced
      compared to that described in non-rheumatoid patients. Rheumatologists and family
      doctors should be aware of the need for post-travel surveillance for
      leishmaniasis in rheumatoid patients on TNF-alpha antagonist treatment. 

PMID- 23972959
TI  - Increased mTORC1 activity contributes to atherosclerosis in apolipoprotein E
      knockout mice and in vascular smooth muscle cells.

PMID- 23972960
TI  - Response to the article: Late onset of coronary vasospasm after administration of
      methyl-ergometrine for gynecologic bleeding [Santoro F, Spennati G, Ieva R, De
      Gennaro L, Correale M, Lopizzo A, Di Biase M, Brunetti ND. Int J Cardiol 2012;
      161: e29-e30].

PMID- 23972961
TI  - Aortic valve stenosis: survey on practice in the north of France.

PMID- 23972962
TI  - Effect of short-term different statins loading dose on renal function and CI-AKI
      incidence in patients undergoing invasive coronary procedures.

PMID- 23972963
TI  - Meeting the challenge: the evolving global landscape of adult congenital heart
      disease.
AB  - BACKGROUND: Only limited information is available on the worldwide distribution
      and volume of adult congenital heart disease (ACHD) centers. We aimed to assess
      the centers using a bibliometric approach. METHODS AND RESULTS: We identified
      publications presenting original research in the field of ACHD between 1995 and
      2011. A total of 94,119 articles were identified which underwent electronic
      filtering and manual review. Overall, a dramatic increase in ACHD publications
      was seen over the study period. This was accompanied by a matching increase in
      impact factors and an over-proportional rise in ACHD contributions relative to
      the general academic field. Research output correlated well with self-reported
      patient volume and the number of identified ACHD centers in Europe and North
      America was in agreement with published surveys, thus validating our methodology.
      We observed a steady increase in the number of publishing ACHD centers worldwide.
      The number of ACHD centers per 10-million population was highest for Europe
      (3.6), followed by North America (1.7), Oceania (1.5), South America (0.4), Asia
      (0.3) and Africa (0.1). In addition, we evaluated the relative research output
      between developed and emerging economies and provide an overview over the main
      areas of research in the ACHD field. CONCLUSIONS: Global interest in ACHD is
      increasing and this is reflected, both, in the number of publishing centers and
      the volume of research. Our data provides insights into the geographical and
      temporal distribution of ACHD research over the last 1 1/2 decades. These results
      could serve as benchmarks for international comparisons and guide efforts for
      improving ACHD infrastructure.

PMID- 23972964
TI  - Bosentan for mild pulmonary vascular disease in ASD patients (the BOMPA trial): a
      double-blind, randomized controlled, pilot trial.

PMID- 23972965
TI  - Depression in cardiovascular patients in the Middle Eastern populations.

PMID- 23972966
TI  - Eplerenone in systemic right ventricle: double blind randomized clinical trial.
      The evedes study.
AB  - BACKGROUND: There is no proven pharmacological strategy for the treatment of the
      failing systemic right ventricle (SRV) but myocardial fibrosis may play a role in
      its pathophysiology. METHODS: We designed a double-blind, placebo-controlled
      clinical trial to assess the effects of eplerenone 50mg during 12 months on
      cardiac magnetic resonance parameters (SRV mass and ejection fraction) and
      neurohormonal and collagen turnover biomarker (CTB) levels. RESULTS: Twenty six
      patients with atrial switch repair for transposition of the great arteries were
      randomized to eplerenone (n=14) or placebo (n=12) and 14 healthy volunteers
      served as controls for comparison of baseline neurohormones and CTB levels. The
      study population showed a good baseline profile in terms of SRV mass (57.4 +/- 17
      g/m(2)) and ejection fraction (54.9 +/- 7.5%). However, levels of N-terminal pro
      brain natriuretic peptide (NT-proBNP), C terminal propeptide of type I
      procollagen (CICP) and C-terminal Telopeptide of type I Collagen (ICTP) were
      significantly elevated when compared to healthy controls. After one year of
      treatment, a trend toward reduction of CICP, N-terminal pro-Matrix
      Metalloproteinase 1 (NT-proMMP1), Tissue Inhibitor of Metalloproteinases 1
      (TIMP1) and galectin 3 levels and a lower increase in ICTP in patients under
      eplerenone was observed. The reduction of SRV mass and the improvement of SRV
      function with eplerenone were not conclusive. CONCLUSIONS: Patients with SRV
      treated with eplerenone showed an improvement of an altered baseline CTB profile
      suggesting that reduction of myocardial fibrosis might be a therapeutic target in
      these patients.

PMID- 23972967
TI  - Methodological considerations and practical recommendations for the application
      of peripheral arterial tonometry in children and adolescents.
AB  - Endothelial dysfunction is recognized as the primum movens in the development of
      atherosclerosis. Its crucial role in both cardiovascular morbidity and mortality
      has been confirmed. In the past, research was hampered by the invasive character
      of endothelial function assessment. The development of non-invasive and feasible
      techniques to measure endothelial function has facilitated and promoted research
      in various adult and paediatric subpopulations. To avoid user dependence of flow
      mediated dilation (FMD), which evaluates nitric oxide dependent vasodilation in
      large vessels, a semi-automated, method to assess peripheral microvascular
      function, called peripheral arterial tonometry (Endo-PAT((r))), was recently
      introduced. The number of studies using this technique in children and
      adolescents is rapidly increasing, yet there is no consensus with regard to
      either measuring protocol or data analysis of peripheral arterial tonometry in
      children and adolescents. Most paediatric studies simply applied measuring and
      analysing methodology established in adults, a simplification that may not be
      appropriate. This paper provides a detailed description of endothelial function
      assessment using the Endo-PAT for researchers and clinicians. We discuss clinical
      and methodological considerations and point out the differences between children,
      adolescents and adults. Finally, the main aim of this paper is to provide
      recommendations for a standardised application of Endo-PAT in children and
      adolescents, as well as for population-specific data analysis methodology. 

PMID- 23972968
TI  - Annual rates of change in pre- vs. post-bronchodilator FEV1 and FVC over 4 years
      in moderate to very severe COPD.
AB  - While the slope of decline in FEV1 has traditionally been calculated from the
      post- rather than the pre-bronchodilator measurement in COPD interventional
      trials, it is not clear whether and to what extent these two slopes differ in
      symptomatic patients with COPD. Therefore, we used data from the 4-year UPLIFT
      trial of tiotropium 18 mcg QD vs. placebo to compare annual rates of change in
      pre- vs. post-bronchodilator FEV1 in 5041 patients with moderate to very severe
      COPD (mean FEV1 48% pred) in whom the post-bronchodilator FEV1 was measured after
      4 inhalations of two different classes of short-acting inhaled bronchodilators at
      baseline and 1 month and every 6 months post-randomization over 4 years. Linear
      mixed effects models were used to estimate annual rates of decline in FEV1 and
      FVC pre- and post-bronchodilator in each treatment group separately, after
      adjusting for height, gender, smoking status, baseline % predicted FEV1 or FVC,
      and baseline acute % improvement in lung function. The slopes of the post
      bronchodilator FEV1 and FVC were significantly steeper than the pre
      bronchodilator slopes regardless of treatment arm (p < 0.001), while the
      estimated variances of the slopes were similar. Post-bronchodilator increases in
      FEV1 and FVC diminished progressively and significantly (p < 0.0001) over the 4
      year trial, suggesting a possible explanation for the significant differences
      between the pre- and post-bronchodilator slopes. While the reasons for these
      differences are not completely clear, they are important to consider when
      assessing treatment effects on rates of decline in FEV1 and FVC.

PMID- 23972969
TI  - Applications of in vivo and in vitro solid-phase microextraction techniques in
      plant analysis: A review.
AB  - As a very popular sample preparation technique, solid-phase microextraction
      (SPME) coupled with various analytical instrumentation, has been widely used for
      the determination of trace levels of different plant compounds, such as volatile
      organic compounds (VOCs) emitted from the different plant organs, and
      environmental contaminants in plants. In this review, recent applications of in
      vitro and in vivo SPME in plant analysis are discussed and summarized according
      to the different organs of plants, including fruits, flowers, leaves, stems,
      roots and seeds, and the whole plant as well. Future developments and
      applications of SPME in plant analysis, especially in vivo sampling approaches,
      are also prospected. 

PMID- 23972970
TI  - Determination of Pd, Rh, Pt, Au in road dust by electrothermal vaporization
      inductively coupled plasma mass spectrometry with slurry sampling.
AB  - Inductively coupled plasma mass spectrometry coupled with ultrasonic slurry
      sampling electrothermal vaporization (USS-ETV-ICP-MS) has been applied to
      determine Pd, Rh, Pt and Au in 0.5% m/v slurries of several road dust samples. 2%
      m/v ammonium pyrrolidine dithiocarbamate (APDC) was used as the modifier to
      enhance the ion count. The influence of instrument operating conditions, slurry
      preparation and interferences on the ion count was reported. This method has been
      applied to the determination of Pd, Rh, Pt and Au in BCR 723 Road Dust and NIST
      SRM 2709 San Joaquin Soil reference materials and two road dust samples collected
      locally. The analysis results of the standard reference materials agreed with the
      certified values. Precision between sample replicates was better than 10% for all
      the determinations. The method detection limits estimated from standard addition
      curves were 0.9, 0.4, 0.6 and 0.4ngg(-1) for Pd, Rh, Pt and Au, respectively, in
      original dust samples. 

PMID- 23972971
TI  - Extension and application of multivariate curve resolution-alternating least
      squares to four-way quadrilinear data-obtained in the investigation of pollution
      patterns on Yamuna River, India--A case study.
AB  - This study focuses on the development and extension of Multivariate Curve
      Resolution-Alternating Least Squares (MCR-ALS) to the analysis of four-way
      datasets. The proposed extension of the MCR-ALS method with non-negativity and
      the newly developed quadrilinear constraints can be exploited to summarize and
      manage huge multidimensional datasets and resolve their four way component
      profiles. In this study, its application is demonstrated by analyzing a four-way
      data set obtained in a long term environmental monitoring study (15 sampling
      sites*9 variables*12 months*7 years) belonging to the Yamuna River, one of the
      most polluted rivers of India and the largest tributary of the Ganges river. MCR
      ALS resolved pollution profiles described appropriately the major observed
      changes on pH, organic pollution, bacteriological pollution and temperature,
      along with their spatial and temporal distribution patterns for the studied
      stretch of Yamuna River. Results obtained by MCR-ALS have also been compared with
      those obtained by another multi-way method, PARAFAC. The methodology used in this
      study is completely general and it can be applied to other multi-way datasets. 

PMID- 23972972
TI  - Automatic identification of novel bacteria using Raman spectroscopy and Gaussian
      processes.
AB  - Raman spectroscopy is successfully used for the reliable classification of
      complex biological samples. Much effort concentrates on the accurate prediction
      of known categories for highly relevant tasks in a wide area of applications such
      as cancer detection and bacteria recognition. However, the resulting recognition
      systems cannot always be directly used in practice since unseen samples might not
      belong to classes present in the training set. Our work aims to tackle this
      problem of novelty detection using a recently proposed approach based on Gaussian
      processes. By learning novelty scores for a large bacteria Raman dataset
      comprising 50 different strains, we analyze the behavior of this method on an
      independent dataset which includes known as well as unknown categories. Our
      experiment reveals that non-parametric methods such as Gaussian processes can be
      successfully applied to the task of finding unknown bacterial strains, leading to
      encouraging results motivating their further utilization in this area. 

PMID- 23972973
TI  - A novel magnetic poly(aniline-naphthylamine)-based nanocomposite for micro solid
      phase extraction of rhodamine B.
AB  - A novel Fe3O4-poly(aniline-naphthylamine)-based nanocomposite was synthesized by
      chemical oxidative polymerization process as a magnetic sorbent for micro solid
      phase extraction. The scanning electron microscopy images of the synthesized
      nanocomposite revealed that the copolymer posses a porous structure with
      diameters less than 50nm. The extraction efficiency of this sorbent was examined
      by isolation of rhodamine B, a mutagenic and carcinogenic dye, from aquatic media
      in dispersion mode. Among different synthesized polymers, Fe3O4/poly(aniline
      naphthylamine) nanocomposite showed a prominent efficiency. Parameters including
      the desorption solvent, amount of sorbent, desorption time, sample pH, ionic
      strength, extraction time and stirring rate were optimized. Under the optimum
      condition, a linear spiked calibration curve in the range of 0.35-5.00MUgL(-1)
      with R(2)=0.9991 was obtained. The limits of detection (3Sb) and limits of
      quantification (10Sb) of the method were 0.10MUgL(-1) and 0.35MUgL(-1) (n=3),
      respectively. The relative standard deviation for water sample with 0.5MUgL(-1)
      of RhB was 4.2% (n=5) and the absolute recovery was 92%. The method was applied
      for the determination of rhodamine B in dishwashing foam, dishwashing liquid,
      shampoo, pencil, matches tips and eye shadows samples and the relative recovery
      percentage were in the range of 94-99%. 

PMID- 23972974
TI  - A sensitive flow-batch system for on board determination of ultra-trace ammonium
      in seawater: Method development and shipboard application.
AB  - Combining fluorescence detection with flow analysis and solid phase extraction
      (SPE), a highly sensitive and automatic flow system for measurement of ultra
      trace ammonium in open ocean water was established. Determination was based on
      fluorescence detection of a typical product of o-phthaldialdehyde and ammonium.
      In this study, the fluorescence reaction product could be efficiently extracted
      onto an SPE cartridge (HLB, hydrophilic-lipophilic balance). The extracted
      fluorescence compounds were rapidly eluted with ethanol and directed into a flow
      cell for fluorescence detection. Compared with the common used fluorescence
      method, the proposed one offered the benefits of improved sensitivity, reduced
      reagent consumption, negligible salinity effect and lower cost. Experimental
      parameters were optimized using a univariate experimental design. Calibration
      curves, ranging from 1.67 to 300nM, were obtained with different reaction times.
      The recoveries were between 89.5 and 96.5%, and the detection limits in land
      based and shipboard laboratories were 0.7 and 1.2nM, respectively. The relative
      standard deviation was 3.5% (n=5) for an aged seawater sample spiked with 20nM
      ammonium. Compared with the analytical results obtained using the indophenol blue
      method coupled to a long-path liquid waveguide capillary cell, the proposed
      method showed good agreement. The method had been applied on board during a South
      China Sea cruise in August 2012. A vertical profile of ammonium in the South East
      Asia Time-Series (SEATS, 18 degrees  N, 116 degrees  E) station was produced. The
      distribution of ammonium in the surface seawater of the Qiongdong upwelling in
      South China Sea is also presented. 

PMID- 23972975
TI  - Matrix-assisted laser desorption ionization mass spectrometry for identification
      of shrimp.
AB  - Matrix-assisted laser desorption ionization (MALDI) time of flight mass
      spectrometry was used to identify shrimp at the species level using commercial
      mass spectral fingerprint matching software (Bruker Biotyper). In the first step,
      a mass spectrum reference database was constructed from the analysis of six
      commercially important shrimp species: Litopenaeus setiferus, Farfantepenaeus
      aztecus, Sicyonia brevirostris, Pleoticus robustus, Pandalopsis dispar and
      Pandalus platyceros. This step required a desalting procedure for optimum
      performance. In the second step, the reference database was tested using 74
      unknown shrimp samples from these six species. Correct identification was
      achieved for 72 of 74 samples (97%): 72 samples were identified at the species
      level and 2 samples were identified at the genus level using the manufacturer's
      log score specifications. The MALDI fingerprinting method for the identification
      of shrimp species was found to be reproducible and accurate with rapid analysis. 

PMID- 23972976
TI  - High-throughput detection of drugs binding to proteins using desorption
      electrospray ionization mass spectrometry.
AB  - In this paper, we present a strategy for screening drugs that bind to proteins by
      combining centrifugal filtration with desorption electrospray ionization mass
      spectrometry (DESI-MS). Membrane filtration was used to remove any unbound drugs.
      Then, drug-protein complexes deposited on the DESI substrate were dissociated
      during the DESI-MS analytical process, and the liberated drugs were measured. To
      validate the methodology, the screening of a series of drugs against two types of
      proteins was performed. Three DNA topoisomerase I (Topo I) inhibitors
      (camptothecin (CPT), hydroxycamptothecin (OHCPT) and 7-ethyl-10
      hydroxycamptothecin (SN-38)) were screened against Topo I and the DNA-Topo I
      complex using DESI-MS. The results indicated that none of the inhibitors bound to
      Topo I, because the inhibitors had binding affinities only to the DNA-Topo I
      complex. Among the three drugs that bound to the DNA-Topo I complex, SN-38 had
      the strongest relative binding affinity, and CPT had the weakest relative binding
      affinity. The impact of the DESI spray solvent composition on the analysis of
      drug-protein complex binding was evaluated. Seven alkaloid drugs were also
      screened against Topo I using DESI-MS. Berberine and palmatine had good binding
      affinities. A screening of 21 types of drugs was carried out to determine whether
      the drugs bound to human serum albumin (HSA). The DESI-MS screening process could
      be achieved within 1.75min. The study provides a method to qualitatively detect
      compounds that bind to proteins, showing great potential in drug design and
      screening. 

PMID- 23972977
TI  - Quantitative structure-ion intensity relationship strategy to the prediction of
      absolute levels without authentic standards.
AB  - The lack of authentic standards represents a major bottleneck in the quantitative
      analysis of complex samples. Here we propose a quantitative structure and
      ionization intensity relationship (QSIIR) approach to predict the absolute levels
      of compounds in complex matrixes. An absolute quantitative method for
      simultaneous quantification of 25 organic acids was firstly developed and
      validated. Napierian logarithm (LN) of the relative slope rate derived from the
      calibration curves was applied as an indicator of the relative ionization
      intensity factor (RIIF) and serves as the dependent variable for building a QSIIR
      model via a multiple linear regression (MLR) approach. Five independent variables
      representing for hydrogen bond acidity, HOMO energy, the number of hydrogen bond
      donating group, the ratio of organic phase, and the polar solvent accessible
      surface area were found as the dominant contributors to the RIIF of organic
      acids. This QSIIR model was validated to be accurate and robust, with the
      correlation coefficients (R(2)), R(2) adjusted, and R(2) prediction at 0.945,
      0.925, and 0.89, respectively. The deviation of accuracy between the predicted
      and experimental value in analyzing a real complex sample was less than 20% in
      most cases (15/18). Furthermore, the high adaptability of this model was
      validated one year later in another LC/MS system. The QSIIR approach is expected
      to provide better understanding of quantitative structure and ionization
      efficiency relationship of analogous compounds, and also to be useful in
      predicting the absolute levels of analogous analytes in complex mixtures. 

PMID- 23972978
TI  - Neurosteroid analysis by gas chromatography-atmospheric pressure photoionization
      tandem mass spectrometry.
AB  - A new and simple APPI interface employing commercially available hardware is used
      to combine GC to MS. The feasibility of the method is demonstrated in the
      analysis of urine samples for neurosteroids as their trimethylsilyl (TMS)
      derivatives. The effect of different dopants (chlorobenzene, toluene, anisole) on
      the ionization of the TMS derivatives was investigated. With chlorobenzene, the
      TMS derivatives produced intense molecular ions with minimal fragmentation, and
      chlorobenzene was selected as best dopant. Protonated molecules in addition to
      intense molecular ions were produced with toluene and anisole. The performance of
      the method was verified in the analysis of human urine samples. Chromatographic
      performance was good with peak half-widths of 3.6-4.3s, linearity (r(2)>0.990)
      was acceptable, limits of detection (LODs) were in the range of 0.01-10ngmL(-1),
      and repeatability was good with relative standard deviations (rsd%) below 22%.
      The results show that the method is well suited for the determination of
      neurosteroids in biological samples. 

PMID- 23972979
TI  - Ammonia-treated N-(1-naphthyl) ethylenediamine dihydrochloride as a novel matrix
      for rapid quantitative and qualitative determination of serum free fatty acids by
      matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron
      resonance mass spectrometry.
AB  - The blood free fatty acids (FFAs), which provide energy to the cell and act as
      substrates in the synthesis of fats, lipoproteins, liposaccharides, and
      eicosanoids, involve in a number of important physiological processes. In the
      present study, matrix-assisted laser desorption/ionization-Fourier transform ion
      cyclotron resonance mass spectrometry (MALDI-FTICR MS) with ammonia-treated N-(1
      naphthyl) ethylenediamine dihydrochloride (ATNEDC) as a novel MALDI matrix in a
      negative ion mode was employed to directly quantify serum FFAs. Multiple point
      internal standard calibration curves between the concentration ratios of
      individual fatty acids to internal standard (IS, C17:0) versus their
      corresponding intensity ratios were constructed for C14:0, C16:1, C16:0, C18:0,
      C18:1, C18:2, C18:3, C20:4, and C22:6, respectively, in their mixture, with
      correlation coefficients between 0.991 and 0.999 and limits of detection (LODs)
      between 0.2 and 5.4MUM, along with the linear dynamic range of more than two
      orders of magnitude. The results indicate that the multiple point internal
      standard calibration could reduce the impact of ion suppression and improve
      quantification accuracy in the MALDI mode. The quantitative results of nine FFAs
      from 339 serum samples, including 161 healthy controls, 118 patients with
      hyperglycemia and 60 patients without hyperglycemia show that FFAs levels in
      hyperglycemic patient sera are significantly higher than those in healthy
      controls and patients without hyperglycemia, and elevated FFA levels are also
      associated with increased levels of fasting blood glucose (FBG) in hyperglycemic
      patient sera. Serum FFAs were identified on the basis of the observed accurate
      molecular masses and reliable isotope distributions obtained by MALDI-FTICR MS. 

PMID- 23972980
TI  - Selective optical sensing of biothiols with Ellman's reagent: 5,5'-Dithio-bis(2
      nitrobenzoic acid)-modified gold nanoparticles.
AB  - Development of sensitive and selective methods of determination for biothiols is
      important because of their significant roles in biological systems. We present a
      new optical sensor using Ellman's reagent (DTNB)-adsorbed gold nanoparticles (Au
      NPs) (DTNB-Au-NP) in a colloidal solution devised to selectively determine
      biologically important thiols (biothiols) from biological samples and
      pharmaceuticals. 5,5'-Dithio-bis(2-nitrobenzoic acid) (DTNB), a versatile water
      soluble compound for quantitating free sulfhydryl groups in solution, was
      adsorbed through non-covalent interaction onto Au-NPs, and the absorbance changes
      associated with the formation of the yellow-colored 5-thio-2-nitrobenzoate (TNB(2
      )) anion as a result of reaction with biothiols was measured at 410nm. The sensor
      gave a linear response over a wide concentration range of standard biothiols
      comprising cysteine, glutathione, homocysteine, cysteamine, dihydrolipoic acid
      and 1,4-dithioerythritol. The calibration curves of individual biothiols were
      constructed, and their molar absorptivities and linear concentration ranges
      determined. The cysteine equivalent thiol content (CETC) values of various
      biothiols using the DTNB-Au-NP assay were comparable to those of the conventional
      DTNB assay, showing that the immobilized DTNB reagent retained its reactivity
      toward thiols. Common biological sample ingredients like amino acids, flavonoids,
      vitamins, and plasma antioxidants did not interfere with the proposed sensing
      method. This assay was validated through linearity, additivity, precision and
      recovery, demonstrating that the assay is reliable and robust. DTNB-adsorbed Au
      NPs probes provided higher sensitivity (i.e., lower detection limits) in biothiol
      determination than conventional DTNB reagent. Under optimized conditions,
      cysteine (Cys) was quantified by the proposed assay, with a detection limit (LOD)
      of 0.57MUM and acceptable linearity ranging from 0.4 to 29.0MUM (r=0.998). 

PMID- 23972981
TI  - Comprehensive review of kinase inhibitor therapy that is long overdue for
      oncologists. Foreword.

PMID- 23972982
TI  - United States Food and Drug Administration approved oral kinase inhibitors for
      the treatment of malignancies.

PMID- 23972983
TI  - Continuing antiplatelet therapy before cardiac surgery with cardiopulmonary
      bypass: a meta-analysis on the need for reexploration and major outcomes.
AB  - OBJECTIVE: To determine major adverse outcomes, including the risk of mediastinal
      reexploration, death, stroke and myocardial infarction, associated with
      continuing antiplatelet therapy in patients undergoing surgery with
      cardiopulmonary bypass. DESIGN: A meta-analysis of parallel randomized,
      controlled trials published in English. SETTING: A university-based electronic
      search. PARTICIPANTS: Patients undergoing surgery with cardiopulmonary bypass
      (CPB). INTERVENTION: Continuing antiplatelet therapy versus stopping antiplatelet
      therapy before the surgery. MEASUREMENTS AND MAIN RESULTS: A search was conducted
      in PubMed, EMBASE, MEDLINE(R), and the Cochrane Central Register of Controlled
      Trials. Twelve studies were retained for analysis. Continuing antiplatelet drugs
      for CPB increases the rate of reexploration by a standardized mean difference
      (SMD) 0.22, 95% confidence interval (CI) 0.06, 0.39; I-square 0%; p value 0.01;
      classical fail-safe number 5. The number needed to harm (NNTH) is 87 (95% CI 390,
      44). There was no statistical difference for death at 30 days and 1 year,
      myocardial infarction at 30 days, and stroke at 30 days. Continuing antiplatelet
      drugs increases blood loss, SMD 0.27 (95% CI 0.09, 0.45), I-square 73.1%; p =
      0.003. CONCLUSIONS: Continuing antiplatelet therapy for patients undergoing
      surgery with CPB is associated with a low risk for reexploration.

PMID- 23972984
TI  - Effects of catecholamines on microcirculation during general inhalation
      anesthesia.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of clinical
      dosages of norepinephrine and dobutamine on sublingual microcirculation during
      general anesthesia with sevoflurane in minor surgical procedures. DESIGN: This
      prospective study was performed on patients scheduled for breast cancer surgery.
      SETTING: Tertiary care university hospital. PARTICIPANTS: Twenty patients
      undergoing elective surgery. INTERVENTIONS: Patients received a continuous
      infusion of norepinephrine (0.1 MUg/kg/min) and afterwards, following a 15-minute
      interval, a continuous infusion of dobutamine (5 MUg/kg/min). Prior to and at the
      end of each drug infusion period, hemodynamic parameters were measured using an
      esophageal Doppler probe (ED), and 5 sidestream darkfield (SDF) sublingual
      microcirculation video recordings were taken. MEASUREMENTS AND MAIN RESULTS: No
      significant changes to total vessel density (TVD)(mm/mm(2)), perfused vessel
      density (PVD) (mm/mm(2)), proportion of perfused vessels (PPV) (percentage), or
      microvascular flow index (MFI) (arbitrary units) were measured at the end of each
      drug infusion period versus pre-infusion data and no differences were observed
      between the effects of norepinephrine versus dobutamine. Mean arterial pressure
      (APm) (mmHg) was significantly greater following both norepinephrine and
      dobutamine infusions compared to pre-infusion values, while peak velocity (PV)
      (cm/sec) and the stroke volume index (SVI) (mL/m(2)) only showed a significant
      increase following the dobutamine infusion. No change in corrected flow time
      (FTc) (msec) was observed. CONCLUSIONS: During general anesthesia with
      sevoflurane, the infusion of clinical dosages of norepinephrine and dobutamine
      did not alter sublingual perfusion, although the expected systemic hemodynamic
      alterations were induced.

PMID- 23972985
TI  - Acute kidney injury and renal regional oxygen saturation during aortic arch
      reconstruction in infants.
AB  - OBJECTIVE: Acute kidney injury is a serious postoperative complication following
      cardiac surgery. The aortic arch repair technique using antegrade selective
      cerebral perfusion has been used, but it is unclear whether subdiaphragmatic
      organs such as the kidneys are perfused adequately. The authors compared
      intraoperative renal regional oxygen saturation using near-infrared spectroscopy
      between infants with and without postoperative acute kidney injury after
      undergoing aortic arch reconstruction. DESIGN: Retrospective medical records
      review. SETTING: University medical center. PARTICIPANTS: Elective cardiac
      surgical infants. INTERVENTIONS: The author reviewed the perioperative clinical
      records of infants who underwent aortic arch reconstruction surgery using
      antegrade selective cerebral perfusion. During the operation, prestenotic (right
      radial or right brachial artery) and poststenotic (femoral or umbilical artery)
      invasive arterial blood pressure and cerebral and renal regional oxygen
      saturation were monitored continuously. Development of acute kidney injury within
      72 hours of surgery was investigated. RESULTS: A total of 47 patients were
      enrolled in this study. Postoperative acute kidney injury occurred in 19 patients
      (40.4%). Intraoperative renal regional oxygen saturation was similar between
      patients with and without acute kidney injury. Intraoperative prestenotic and
      poststenotic mean arterial blood pressure and cerebral regional oxygen saturation
      also were similar between the 2 groups. CONCLUSIONS: The intraoperative renal
      tissue oxygen saturation was not different between the groups with or without
      postoperative acute kidney injury in infants who underwent aortic arch repair
      using antegrade selective cerebral perfusion.

PMID- 23972986
TI  - Grk5l controls heart development by limiting mTOR signaling during symmetry
      breaking.
AB  - The correct asymmetric placement of inner organs is termed situs solitus and is
      determined early during development. Failure in symmetry breaking results in
      conditions ranging from randomized organ arrangement to a complete mirror image,
      often accompanied by severe congenital heart defects (CHDs). We found that the
      zebrafish homolog of mammalian G protein-coupled receptor kinase 5 (GRK5) employs
      noncanonical, receptor-independent functions to secure symmetry breaking.
      Knockdown of GRK5's closest homolog in zebrafish embryos, Grk5l, is sufficient to
      randomize cardiac looping and left-right asymmetry. Mechanistically, we found
      that loss of GRK5 increases mammalian target of rapamycin complex 1 (mTORC1)
      activity. This causes elongation of motile cilia in the organ of laterality, a
      consequence that is known to be sufficient to trigger aberrant organ arrangement.
      By fine-tuning mTORC1, GRK5 thus serves an unanticipated function during early
      development, besides its well-characterized role in the adult heart. These
      findings could implicate GRK5 as a susceptibility allele for certain cases of
      CHD. 

PMID- 23972987
TI  - Conserved regulation of the Jak/STAT pathway by the endosomal protein asrij
      maintains stem cell potency.
AB  - Asrij/OCIAD1 is an endosomal protein expressed in stem cells and cardiovascular
      lineages and aberrantly expressed in several cancers. We show that dose-dependent
      modulation of cytokine-dependent JAK/STAT signaling by Asrij regulates mouse
      embryonic stem cell pluripotency as well as Drosophila hematopoietic stem cell
      maintenance. Furthermore, mouse asrij can substitute for Drosophila asrij,
      indicating that they are true homologs. We identify a conserved region of Asrij
      that is necessary and sufficient for vesicular localization and function. We also
      show that Asrij and STAT3 colocalize in endosomes and interact biochemically. We
      propose that Asrij provides an endosomal scaffold for STAT3 interaction and
      activation, and may similarly control other circuits that maintain stemness.
      Thus, Asrij provides a key point of control for spatial and kinetic regulation of
      stem cell signals. 

PMID- 23972988
TI  - Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell
      intrinsic antiviral response.
AB  - Aicardi-Goutieres syndrome (AGS), a hereditary autoimmune disease, clinically and
      biochemically overlaps with systemic lupus erythematosus (SLE) and, like SLE, is
      characterized by spontaneous type I interferon (IFN) production. The finding that
      defects of intracellular nucleases cause AGS led to the concept that
      intracellular accumulation of nucleic acids triggers inappropriate production of
      type I IFN and autoimmunity. AGS can also be caused by defects of SAMHD1, a 3'
      exonuclease and deoxynucleotide (dNTP) triphosphohydrolase. Human SAMHD1 is an
      HIV-1 restriction factor that hydrolyzes dNTPs and decreases their concentration
      below the levels required for retroviral reverse transcription. We show in gene
      targeted mice that also mouse SAMHD1 reduces cellular dNTP concentrations and
      restricts retroviral replication in lymphocytes, macrophages, and dendritic
      cells. Importantly, the absence of SAMHD1 triggered IFN-beta-dependent
      transcriptional upregulation of type I IFN-inducible genes in various cell types
      indicative of spontaneous IFN production. SAMHD1-deficient mice may be
      instrumental for elucidating the mechanisms that trigger pathogenic type I IFN
      responses in AGS and SLE. 

PMID- 23972989
TI  - Regulation of cyclic AMP response element binding and hippocampal plasticity
      related genes by peroxisome proliferator-activated receptor alpha.
AB  - Peroxisome proliferator-activated receptor alpha (PPARalpha) is a transcription
      factor that regulates genes involved in fatty acid catabolism. Here, we provide
      evidence that PPARalpha is constitutively expressed in nuclei of hippocampal
      neurons and, surprisingly, controls calcium influx and the expression of various
      plasticity-related genes via direct transcriptional regulation of cyclic AMP
      response element binding (CREB). Accordingly, Pparalpha-null, but not Pparbeta
      null, mice are deficient in CREB and memory-associated proteins and have
      decreased spatial learning and memory. Small hairpin RNA knockdown of PPARalpha
      in the hippocampus suppressed CREB and NR2A, rendering wild-type animals markedly
      poor in consolidating spatial memory, whereas introduction of PPARalpha to the
      hippocampus of Pparalpha-null mice increased hippocampal CREB and NR2A and
      improved spatial learning and memory. Through detailed analyses of CREB and NR2A
      activity, as well as spatial learning and memory in bone marrow chimeric animals
      lacking PPARalpha in the CNS, we uncover a mechanism for transcriptional control
      of Creb and associated plasticity genes by PPARalpha. 

PMID- 23972990
TI  - Opposing effect of EGFRWT on EGFRvIII-mediated NF-kappaB activation with RIP1 as
      a cell death switch.
AB  - RIP1 is a central mediator of cell death in response to cell stress but can also
      mediate cell survival by activating NF-kappaB. Here, we show that RIP1 acts as a
      switch in EGFR signaling. EGFRvIII is an oncogenic mutant that does not bind
      ligand and is coexpressed with EGFRWT in glioblastoma multiforme (GBM). EGFRvIII
      recruits ubiquitin ligases to RIP1, resulting in K63-linked ubiquitination of
      RIP1. RIP1 binds to TAK1 and NEMO, forming an EGFRvIII-RIP1 signalosome that
      activates NF-kappaB. RIP1 is essential for EGFRvIII-mediated oncogenicity and
      correlates with NF-kappaB activation in GBM. Surprisingly, activation of EGFRWT
      with EGF results in a negative regulation of EGFRvIII, with dissociation of the
      EGFRvIII-RIP1 signalosome, loss of RIP1 ubiquitination and NF-kappaB activation,
      and association of RIP1 with FADD and caspase-8. If EGFRWT is overexpressed with
      EGFRvIII, the addition of EGF leads to a RIP1 kinase-dependent cell death. The
      EGFRWT-EGFRvIII-RIP1 interplay may regulate oncogenicity and vulnerability to
      targeted treatment in GBM. 

PMID- 23972991
TI  - RIP3 inhibits inflammatory hepatocarcinogenesis but promotes cholestasis by
      controlling caspase-8- and JNK-dependent compensatory cell proliferation.
AB  - For years, the term "apoptosis" was used synonymously with programmed cell death.
      However, it was recently discovered that receptor interacting protein 3 (RIP3)
      dependent "necroptosis" represents an alternative programmed cell death pathway
      activated in many inflamed tissues. Here, we show in a genetic model of chronic
      hepatic inflammation that activation of RIP3 limits immune responses and
      compensatory proliferation of liver parenchymal cells (LPC) by inhibiting Caspase
      8-dependent activation of Jun-(N)-terminal kinase in LPC and nonparenchymal liver
      cells. In this way, RIP3 inhibits intrahepatic tumor growth and impedes the
      Caspase-8-dependent establishment of specific chromosomal aberrations that
      mediate resistance to tumor-necrosis-factor-induced apoptosis and underlie
      hepatocarcinogenesis. Moreover, RIP3 promotes the development of jaundice and
      cholestasis, because its activation suppresses compensatory proliferation of
      cholangiocytes and hepatic stem cells. These findings demonstrate a function of
      RIP3 in regulating carcinogenesis and cholestasis. Controlling RIP3 or Caspase-8
      might represent a chemopreventive or therapeutic strategy against hepatocellular
      carcinoma and biliary disease. 

PMID- 23972992
TI  - Response to the dorsal anterior gradient of EGFR signaling in Drosophila
      oogenesis is prepatterned by earlier posterior EGFR activation.
AB  - Spatially restricted epidermal growth factor receptor (EGFR) activity plays a
      central role in patterning the follicular epithelium of the Drosophila ovary. In
      midoogenesis, localized EGFR activation is achieved by the graded dorsal anterior
      localization of its ligand, Gurken. Graded EGFR activity determines multiple
      dorsal anterior fates along the dorsal-ventral axis but cannot explain the sharp
      posterior limit of this domain. Here, we show that posterior follicle cells
      express the T-box transcription factors Midline and H15, which render cells
      unable to adopt a dorsal anterior fate in response to EGFR activation. The
      posterior expression of Midline and H15 is itself induced in early oogenesis by
      posteriorly localized EGFR signaling, defining a feedback loop in which early
      induction of Mid and H15 confers a molecular memory that fundamentally alters the
      outcome of later EGFR signaling. Spatial regulation of the EGFR pathway thus
      occurs both through localization of the ligand and through localized regulation
      of the cellular response. 

PMID- 23972993
TI  - SCF-mediated Cdh1 degradation defines a negative feedback system that coordinates
      cell-cycle progression.
AB  - Proper cell-cycle transitions are driven by waves of ubiquitin-dependent
      degradation of key regulators by the anaphase-promoting complex (APC) and Skp1
      Cullin1-F-box (SCF) E3 ubiquitin ligase complexes. But precisely how APC and SCF
      activities are coordinated to regulate cell-cycle progression remains largely
      unclear. We previously showed that APC/Cdh1 earmarks the SCF component Skp2 for
      degradation. Here, we continue to report that SCF(beta-TRCP) reciprocally
      controls APC/Cdh1 activity by governing Cdh1 ubiquitination and subsequent
      degradation. Furthermore, we define both cyclin A and Plk1, two well-known Cdh1
      substrates, as upstream modifying enzymes that promote Cdh1 phosphorylation to
      trigger Cdh1 ubiquitination and subsequent degradation by SCF(beta-TRCP). Thus,
      our work reveals a negative repression mechanism for SCF to control APC, thereby
      illustrating an elegant dual repression system between these two E3 ligase
      complexes to create the ordered cascade of APC and SCF activities governing
      timely cell-cycle transitions. 

PMID- 23972994
TI  - ABH2 couples regulation of ribosomal DNA transcription with DNA alkylation
      repair.
AB  - Transcription has been linked to DNA damage. How the most highly transcribed
      mammalian ribosomal (rDNA) genes maintain genome integrity in the absence of
      transcription-coupled DNA damage repair is poorly understood. Here, we report
      that ABH2/ALKBH2, a DNA alkylation repair enzyme, is highly enriched in the
      nucleolus. ABH2 interacts with DNA repair proteins Ku70 and Ku80 as well as
      nucleolar proteins nucleolin, nucleophosmin 1, and upstream binding factor (UBF).
      ABH2 associates with and promotes rDNA transcription through its DNA repair
      activity. ABH2 knockdown impairs rDNA transcription and leads to increased single
      stranded and double-stranded DNA breaks that are more pronounced in the rDNA
      genes, whereas ABH2 overexpression protects cells from methyl-methanesulfonate
      induced DNA damage and inhibition of rDNA transcription. In response to massive
      alkylation damage, ABH2 rapidly redistributes from the nucleolus to nucleoplasm.
      Our study thus reveals a critical role of ABH2 in maintaining rDNA gene integrity
      and transcription and provides insight into the ABH2 DNA repair function. 

PMID- 23972996
TI  - Commentary on 'electrical potentials between stent-grafts made from different
      metals induce negligible corrosion'.

PMID- 23972995
TI  - Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor
      alpha2.
AB  - Members of the 18 glycosyl hydrolase (GH 18) gene family have been conserved over
      species and time and are dysregulated in inflammatory, infectious, remodeling,
      and neoplastic disorders. This is particularly striking for the prototypic
      chitinase-like protein chitinase 3-like 1 (Chi3l1), which plays a critical role
      in antipathogen responses where it augments bacterial killing while stimulating
      disease tolerance by controlling cell death, inflammation, and remodeling.
      However, receptors that mediate the effects of GH 18 moieties have not been
      defined. Here, we demonstrate that Chi3l1 binds to interleukin-13 receptor alpha2
      (IL-13Ralpha2) and that Chi3l1, IL-13Ralpha2, and IL-13 are in a multimeric
      complex. We also demonstrate that Chi3l1 activates macrophage mitogen-activated
      protein kinase, protein kinase B/AKT, and Wnt/beta-catenin signaling and
      regulates oxidant injury, apoptosis, pyroptosis, inflammasome activation,
      antibacterial responses, melanoma metastasis, and TGF-beta1 production via IL
      13Ralpha2-dependent mechanisms. Thus, IL-13Ralpha2 is a GH 18 receptor that plays
      a critical role in Chi3l1 effector responses. 

PMID- 23972997
TI  - Similar semiology of epileptic and psychogenic nonepileptic seizures recorded
      during stereo-EEG.
AB  - We report two adolescents with refractory seizure disorders in whom both
      epileptic and psychogenic nonepileptic seizures (PNES) were recorded with
      intracerebral EEG. The ictal phenomenology of epileptic seizures (ES) and PNES,
      consisting of hypermotor attacks in the first patient and left-sided painful
      episodes in the second patient, proved remarkably similar in both cases,
      highlighting the difficulties which can arise with the distinction of epileptic
      seizures and PNES based on ictal phenomenology alone. 

PMID- 23972998
TI  - Terminology should be as simple as possible and should express the concepts
      clearly.

PMID- 23973001
TI  - Complications of upper cervical spine trauma in elderly subjects. A systematic
      review of the literature.
AB  - The frequency of cervical spine trauma in elderly patients is increasing with
      most injuries occurring in the upper cervical spine. These fractures are
      associated with a risk of sometimes life-threatening complications, although very
      few studies have specifically analyzed this. The goal of this study was to
      identify the incidence of complications in the literature (mortality and
      morbidity) following upper cervical spine trauma in elderly patients. METHODS: A
      systematic search was performed on the MEDLINE database without limiting the
      search by language or date to identify all studies reporting the rate of
      complications after upper cervical spine trauma in patients over the age of 60.
      RESULTS: Twenty-four observational studies were included, four were comparative.
      These studies included a total of 857 patients, mean age 76. Nearly all traumas
      were odontoid process fractures, and most were treated surgically (57%). The
      median mortality rate was 9.2% (Q1-Q3: 2.5-19.6) and the median rate of short
      term complications was 15.4% (Q1-Q3: 5.8-26.9). The main late stage complication
      was nonunion, which developed in a mean 10 to 12% depending on the type of
      treatment. CONCLUSION: Complications following cervical spine trauma are frequent
      in elderly patients whatever the type of treatment. Knowledge of the rate of
      complications in the literature and the potential risk factors is essential for
      the clinician to improve the information provided to patients and to prevent
      complications. TYPE OF STUDY: Systematic review of the literature. Level of
      evidence IV.

PMID- 23973000
TI  - The role of chitosan as nanofiller of graphite oxide for the removal of toxic
      mercury ions.
AB  - The present study focuses on the role of chitosan (CS) as nanofiller of graphite
      oxide (GO) in order to prepare composite materials with improved Hg(II)
      adsorption properties. The removal of Hg(II) from aqueous solutions was studied
      using adsorbents as graphite oxide (GO), graphite oxide nanofilled with chitosan
      (GO/CS) and magnetic chitosan (GO/mCS). Many possible interactions between
      materials and Hg(II) were observed after adsorption and explained via
      characterization with various techniques (SEM/EDAX, FTIR, XRD, DTG). The
      adsorption evaluation was done studying various parameters as the effect of pH
      (both in adsorption and desorption), contact time (pseudo-second order fitting),
      temperature (isotherms at 25, 45, 65  degrees C), in line with a brief
      thermodynamic analysis (DeltaG(0), DeltaH(0), DeltaS(0)). The maximum adsorption
      capacity (fitting with Langmuir model) of GO at 25  degrees C was Qmax=187 mg/g,
      while after the CS nanofilling (formation of the composite GO/CS), Qmax was
      increased to 381 mg/g with a further enhancement for GO/mCS (Qmax=397 mg/g).

PMID- 23972999
TI  - Is the relationship between early-onset cannabis use and educational attainment
      causal or due to common liability?
AB  - BACKGROUND: Several studies have shown that early cannabis use is correlated with
      poor educational performance including high school drop-out. The predominant
      explanation for this relationship is that cannabis use causes disengagement from
      education. Another explanation is that the association between early cannabis use
      and educational attainment is not causal, but the result of overlapping risk
      factors that increase the likelihood of both early cannabis use and disengagement
      from education. These confounding factors could be of genetic and/or
      environmental origin. METHODS: Here we use data from a large community-based
      sample of adult twins (N=3337) who completed a comprehensive semi-structured
      telephone interview. We first apply the classical twin-design to determine
      whether genetic and/or environmental influences underlie the relationship between
      early-onset cannabis use (prior to age 18) and early school leaving. Next, with a
      co-twin control design we investigate whether the relationship between the two
      variables is more likely due to direct causality or overlapping risk factors.
      RESULTS: We find a significant phenotypic correlation between early-onset
      cannabis use and early school leaving (r=0.26), which could be explained by
      familial influences (of genetic and/or shared environmental origin). The pattern
      of odds ratios found in the co-twin control design is not consistent with direct
      causation, but rather suggests that the association is due to shared
      environmental factors influencing both variables. CONCLUSION: Our findings
      suggest that the relationship between early-onset cannabis use and school leaving
      is due to shared environmental risk factors influencing both the risk of early
      onset cannabis use and early school leaving.

PMID- 23973002
TI  - A case for critical ethnography: rethinking the early years of the AIDS epidemic
      in South Africa.
AB  - The epidemic of AIDS in South Africa has been characterized not only by its rapid
      progression but also its impassioned controversies. Retrospectively examining a
      long-term anthropological project and discussing some reactions it elicited, the
      paper proposes a defense and illustration of a critical ethnography at three
      moments of the research. Ethnography is first discussed as fieldworks, proposing
      an alternative to the horizontal multi-sited approach via a vertical multi
      layered method using various scales and locations, and thus connecting the
      disease endured by patients in townships and former homelands with the heated
      debates in scientific and political forums: this procedure substitutes a
      political economy of the disease for its cultural and behavioral interpretations.
      Ethnography is then discussed as writing, suggesting acknowledgment of the social
      intelligence of the agents as well as the need for a scientific distance: this
      principle allows the articulation of the objective historical condition of the
      individuals and their subjective experience of history, both revealed in the
      development of the epidemic. Ultimately ethnography is considered from the
      perspective of its afterlife, that is, the continuous process of its translation
      by readers and commentators, on the one hand, by the author trying to reach
      beyond the boundaries of the academic realm, on the other, the work of
      anthropology appearing as a living object open to public conversation and
      consequently a resource for knowledge and action. 

PMID- 23973004
TI  - Up to date on primary ciliary dyskinesia in children.
AB  - Primary ciliary dyskinesia (PCD) is a congenital, clinically and
      ultrastructurally heterogeneous disease due to abnormal structure and/or function
      of cilia, with impaired mucociliary transport leading to several respiratory
      disorders. PCD can be diagnosed by the combination of thorough clinical
      examination with functional and ultrastructural analysis of the cilia. This paper
      shows progresses in PCD diagnosis obtained by ciliogenesis in culture evaluation
      of ciliated respiratory cells and by genetic analysis of mutations in candidate
      genes. Moreover, since to date no specific treatments are available to correct
      the ciliary dysfunction, the paper shows the proper therapeutical approach by the
      use of respiratory physiotherapy and regular exercise to favour airways
      clearance, by antibiotics administration to control acute airway infections.
      Macrolides administration as antiinflammatory option is suggested.

PMID- 23973003
TI  - Interstitial lung disease in children.
AB  - Children's interstitial lung disease (ILD) includes a wide range of rare
      respiratory disorders associated with high morbidity and mortality. Genetic
      factors, systemic disease processes, nonspecific inflammatory or fibrotic
      patterns of repair seen in a number of clinical settings are involved in the ILD
      pathogenesis. Specific disorders more prevalent in young children include diffuse
      developmental disorders, alveolar growth abnormalities, genetic surfactant
      disorders, pulmonary interstitial glycogenosis and neuroendocrine cell
      hyperplasia of infancy. It may be difficult to recognize these entities and this
      can lead to delayed treatment. The diagnostic approach is based on a combination
      of history/physical examinations, imaging studies, pulmonary function testing,
      genetic testing, bronchoalveolar lavage (BAL) and in most cases an open lung
      biopsy. Although some disease types overlap with those seen in adults, in this
      review emphasis is placed on entities unique to the pediatric population focusing
      on clinical characteristics, histologic definitions, radiologic-pathologic
      correlation and therapeutic strategies. 

PMID- 23973005
TI  - Flux-limited diffusion equation: comment on "Morphogenetic action through flux
      limited spreading", by Verbeni M., Sanchez O., Mollica E., Siegl-Cachedernier I.,
      Carleton A., Guerrero I., Ruiz i Altaba A., Soler J.

PMID- 23973006
TI  - Proving lightning role in the evolution of life: comment on "Lightning-triggered
      electroporation and electrofusion as possible contributors to natural horizontal
      gene transfer" by Tadej Kotnik.

PMID- 23973007
TI  - The bilingual brain: flexibility and control in the human cortex.
AB  - The goal of the present review is to discuss recent cognitive neuroscientific
      findings concerning bilingualism. Three interrelated questions about the
      bilingual brain are addressed: How are multiple languages represented in the
      brain? how are languages controlled in the brain? and what are the real-world
      implications of experience with multiple languages? The review is based on
      neuroimaging research findings about the nature of bilingual processing, namely,
      how the brain adapts to accommodate multiple languages in the bilingual brain and
      to control which language should be used, and when. We also address how this
      adaptation results in differences observed in the general cognition of bilingual
      individuals. General implications for models of human learning, plasticity, and
      cognitive control are discussed. 

PMID- 23973008
TI  - First principles theories for last name dynamics.

PMID- 23973009
TI  - Interventions to prevent HIV and Hepatitis C in people who inject drugs: a review
      of reviews to assess evidence of effectiveness.
AB  - BACKGROUND: Injecting drug use is a major risk factor for the acquisition and
      transmission of HIV and Hepatitis C virus (HCV). Prevention of these infections
      among people who inject drugs (PWID) is critical to reduce ongoing transmission,
      morbidity and mortality. METHODS: A review of reviews was undertaken involving
      systematic literature searches of Medline, Embase, CINAHL, PsychINFO, IBSS and
      the Cochrane Library (2000-2011) to identify English language reviews regarding
      the effectiveness of harm reduction interventions in relation to HIV
      transmission, HCV transmission and injecting risk behaviour (IRB). Interventions
      included needle and syringe programmes (NSP); the provision of injection
      paraphernalia; opiate substitution treatment (OST); information, education and
      counselling (IEC); and supervised injecting facilities (SIFs). Reviews were
      classified into 'core' or 'supplementary' using critical appraisal criteria, and
      the strength of review-level evidence was assessed. RESULTS: Twelve core and
      thirteen supplementary reviews were included. From these reviews we identified:
      (i) for NSP: tentative review-level evidence to support effectiveness in reducing
      HIV transmission, insufficient review-level evidence relating to HCV
      transmission, but sufficient review-level evidence in relation to IRB; (ii) for
      OST: sufficient review-level evidence of effectiveness in relation to HIV
      transmission and IRB, but tentative review-level evidence in relation to HCV
      transmission; (iii) for IEC, the provision of injection paraphernalia and SIFs:
      tentative review-level evidence of effectiveness in reducing IRB; and either
      insufficient or no review-level evidence for these interventions in relation to
      HIV or HCV transmission. CONCLUSION: Review-level evidence indicates that harm
      reduction interventions can reduce IRB, with evidence strongest for OST and NSP.
      However, there is comparatively little review-level evidence regarding the
      effectiveness of these interventions in preventing HCV transmission among PWID.
      Further studies are needed to assess the effectiveness and impact of scaling up
      comprehensive packages of harm reduction interventions to minimise HIV and HCV
      transmission among PWID.

PMID- 23973011
TI  - Evidence of birth seasonality and clustering of Mycobacterium avium subspecies
      paratuberculosis infection in US dairy herds.
AB  - Paratuberculosis (Johne's disease) is a contagious intestinal infection of
      ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). In
      cattle, young calves are at the highest risk for acquiring the infection which
      occurs mainly through ingestion of MAP from contaminated milk, colostrum and
      feces or environmental contacts. Data consisted of birth dates and ELISA results
      of 8000 mature cows from 24 Jersey herds from throughout the US and 4 Wisconsin
      Holstein herds. Some herds also had complete fecal culture (FC) results. The
      first infection (case) definition (CD1) relied on only ELISA results. A second
      case definition (CD2) was used in which results of both ELISA and FC tests were
      considered: animals testing positive to either test were considered "test
      positives" and cows testing negative to ELISA or to both ELISA and FC were
      regarded as "test-negatives". Objective one was to assess seasonality in birth of
      MAP-infected animals. The effects of age, breed, herd and season of birth
      (expressed as the sine and cosine functions of birth days within year) were
      examined using logistic regression. Age was significantly associated with the MAP
      infection status of dairy cows for both CDs (OR=1.11; 95% CI 1.09, 1.14; P<0.0001
      for CD1; OR=1.16; 95% CI 1.08, 1.24; P<0.0001 for CD2). Season of birth had a
      significant effect on the risk of MAP infection based on CD1 (OR=0.79; 95% CI
      0.71, 0.89; P<0.001 for cosine of birth days) with a peak in summer and a trough
      in winter based on the fitted model. Objective two was to assess whether test
      positive animals were randomly distributed or were clustered by date of birth
      within herds. A temporal cluster analysis approach (scan statistic) implemented
      in SaTScan software was used for each case definition to detect clusters of birth
      cohorts using birthdates. Results identified significant clustering of MAP
      infection cases for CD1 in multiple herds (P<0.05). These results necessitate
      matching cases and controls of MAP infection on their birth dates to control for
      non-uniform exposure to MAP in paratuberculosis case-control genome wide
      association studies, candidate gene studies or in on-farm disease intervention
      trials. 

PMID- 23973010
TI  - A pilot study of eptifibatide for treatment of acute pain episodes in sickle cell
      disease.
AB  - INTRODUCTION: The contribution of platelet activation to the pathogenesis of
      sickle cell disease (SCD) remains uncertain. We evaluated the safety and efficacy
      of eptifibatide, a synthetic peptide inhibitor of the alphaIIbbeta3 receptor, in
      SCD patients during acute painful episodes. MATERIALS AND METHODS: In this single
      site, double-blind, placebo-controlled trial, eligible patients with SCD admitted
      for acute painful episodes were randomized to receive eptifibatide or placebo at
      a ratio of 2:1. RESULTS: Thirteen patients (SS - 10, Sbeta(0) - 2, SC - 1) were
      randomized to receive either eptifibatide (N=9; 6 females; median age - 25years)
      or placebo (N=4; 3 females; median age - 31years). In the intent-to-treat
      analysis, there were no major bleeding episodes in either the eptifibatide or
      placebo arms (point estimate of difference: 0.00, 95% CI; -0.604, 0.372). There
      was one minor bleeding episode in the eptifibatide arm (point estimate of
      difference for any bleeding: 0.11, 95% CI: -0.502, 0.494). There was no
      significant difference in the proportion of patients with thrombocytopenia
      between the treatment groups (point estimate of difference: 0.11, 95% CI: -0.587,
      0.495). There were no differences in the median times to discharge, median times
      to crisis resolution or the median total opioid use. CONCLUSIONS: In this small
      study, eptifibatide appeared to be safe, but did not improve the times to crisis
      resolution or hospital discharge. Adequately powered studies are required to
      evaluate the safety and efficacy of eptifibatide in SCD. Clinicaltrials.gov
      Identifier: NCT00834899.

PMID- 23973012
TI  - Free-roaming dog populations: a cost-benefit model for different management
      options, applied to Abruzzo, Italy.
AB  - Since 1991, Italian free-roaming dogs have been under government protection and
      euthanasia is restricted by law. Management measures are regulated at the
      regional level and include: kennelling, adoptions, conversion of stray dogs into
      block dogs, and population control of owned dogs. "Block dogs" are free-roaming
      dogs that have been collected by the veterinary services, microchipped,
      sterilised, vaccinated, and released under the responsibility of the local
      municipalities. The present paper describes a cost-benefit model for different
      management options and applies it to two provinces in Abruzzo, central Italy. The
      model considers welfare, nuisance and direct costs to the municipality. Welfare
      is quantified based on the expert opinions of 60 local veterinarians, who were
      asked to assign a score for each dog category according to the five freedoms:
      freedom from pain, physical discomfort, disease, fear, and freedom to express
      normal behaviour. Nuisance was assessed only for comparisons between management
      options, using the number of free-roaming dogs per inhabitant as a proxy
      indicator. A community dog population model was constructed to predict the effect
      of management on the different subpopulations of dogs during a ten-year period.
      It is a user-friendly deterministic model in Excel, easily adaptable to different
      communities to assess the impact of their dog management policy on welfare,
      nuisance and direct monetary cost. We present results for Teramo and Pescara
      provinces. Today's management system is compared to alternative models, which
      evaluate the effect of specific interventions. These include either a 10% yearly
      increase in kennel capacity, an increase in adoptions from kennels, a doubling of
      the capture of stray dogs, or a stabilisation of the owned dog population.
      Results indicate that optimal management decisions are complex because welfare,
      nuisance and monetary costs may imply conflicting interventions. Nevertheless,
      they clearly indicate that management actions that would act on dog ownership
      patterns to reduce the number of free-roaming dogs would have the most favourable
      outcomes. These include reducing the reproductive capacity of the owned dog
      population, stronger enforcement of mandatory dog identification, reducing
      abandonment and increasing adoptions. This would increase welfare and free
      resources for implementing public campaigns. Block dogs may be an important
      intermediary means to reduce stray dogs, but adoption would be preferable. 

PMID- 23973013
TI  - Clinical features and nigrostriatal dysfunction in patients with combined
      postural and resting tremors.
AB  - BACKGROUND: The characteristics of clinical features and nigrostriatal
      dopaminergic dysfunction in patients with combined postural and resting tremors
      have been less clearly reported. METHODS: The present study examined 43 patients
      with a visible persistent bilateral postural tremor and a unilateral/bilateral
      resting tremor involving the hands and forearms. The patients had experienced
      tremors for more than 3 years, with no evidence of Parkinson's disease or other
      parkinsonian disorders. Visual and quantitative analyses of [18F] N-(3
      fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET in
      36 patients were performed. Seventeen age-matched normal controls were also
      studied. RESULTS: On visual analysis, 28 patients (78%) showed normal [18F] FP
      CIT uptake and eight (22%) showed significantly reduced uptake, suggesting
      nigrostriatal dopaminergic neuronal degeneration. The reduced [18F] FP-CIT uptake
      was significantly associated with earlier age-at-onset of tremor and asymmetric
      presentation of resting tremor. On quantitative analysis, there were
      statistically significant differences in the [18F] FP-CIT uptake ratio in the
      posterior putamen between patients with reduced uptake (2.37 +/- 1.83) and
      patients with normal uptake (6.39 +/- 1.35) (P < 0.001). However, posterior
      putamen uptake levels in patients with normal [18F] FP-CIT uptake on visual
      analysis were similar to those in normal controls (7.22 +/- 1.29) (P = 0.291).
      CONCLUSION: The nigrostriatal dopaminergic dysfunction in patients with combined
      postural and resting tremors may be associated with earlier age-at-onset of
      tremor and asymmetric pattern of resting tremor, which might help to correctly
      diagnose patients with mixed tremors.

PMID- 23973014
TI  - Zoophilia and Parkinson's disease.

PMID- 23973015
TI  - Sequential determination of new peptaibols asperelines G-Z12 produced by marine
      derived fungus Trichoderma asperellum using ultrahigh pressure liquid
      chromatography combined with electrospray-ionization tandem mass spectrometry.
AB  - Thirty-eight short peptaibols in a microheterogeneous mixture derived from the
      fermentation broth of a marine-derived fungus Trichoderma asperellum were
      determined using ultrahigh pressure liquid chromatography in combination with
      electrospray-ionization tandem mass spectrometry (UHPLC-ESIMS/MS) techniques,
      including thirty-two new peptaibols namely asperelines G-Z13. The C-terminus
      bonded to proline (aspereline Z9) or hydroxyprolinol (aspereline Z12) is rarely
      found in nature. So far, it is the largest number of peptaibols to be detected at
      once on the basis of the selected ion monitoring (SIM) mode coupled to precursor
      scan techniques. 

PMID- 23973016
TI  - Effect of brachytherapy technique and patient characteristics on cervical cancer
      implant dosimetry.
AB  - Our purpose was to evaluate the relationship between brachytherapy technique and
      patient characteristics on dose to organs-at-risk (OARs) in patients undergoing
      high dose rate (HDR) brachytherapy for cervical cancer. From 1998 to 2008, 31
      patients with cervical cancer with full dosimetric data were identified who
      received definitive external-beam radiation and HDR brachytherapy with tandem and
      ovoid applicators. Doses were recorded at point A, the International Commission
      on Radiation Units and Measurements (ICRU)-38 rectal point, the ICRU-38 bladder
      point, the vaginal surface, and the pelvic sidewall. Generalized estimating
      equations were used to determine the significance of changes in OAR to point A
      dose ratios with differences in brachytherapy technique or patient
      characteristics. Patients underwent a median of 5 brachytherapy procedures
      (range, 3 to 5), with a total of 179 procedures for 31 patients. For all
      brachytherapy treatments, the average ratios between the doses for the rectal,
      bladder, vaginal surface, and pelvic sidewall reference points to those at point
      A were 0.49, 0.59, 1.15, and 0.17, respectively. In general, decreased OAR dose
      was associated with a lower stage, younger age, increased ovoid size, increased
      tandem length, and earlier implant number. Increased tandem curvature
      significantly increased bladder dose and decreased rectal dose. Intravenous
      anesthesia usage was not correlated with improved dosimetry. This study allowed
      identification of patient and procedure characteristics influencing OAR dosing.
      Although the advent of 3-dimensional (3D) image-guided brachytherapy will bring
      new advances in treatment optimization, the actual technique involved at the time
      of the brachytherapy implant procedure will remain important. 

PMID- 23973017
TI  - Comparison of whole-field simultaneous integrated boost VMAT and IMRT in the
      treatment of nasopharyngeal cancer.
AB  - To study the feasibility of using volumetric-modulated arc therapy (VMAT) to
      deliver whole-field simultaneous integrated boost (WF-SIB) to treat patients with
      nasopharyngeal cancer (NPC). WF-SIB intensity-modulated radiotherapy (IMRT)
      plans, one-arc WF-SIB VMAT plans, and two-arc WF-SIB VMAT plans were generated
      with identical objective functions for 8 patients with NPC of various stages.
      Isodose distributions and dose-volume histograms were evaluated. Dosimetric and
      biological quality indices of clinical target volume (CTV) and organs at risk
      (OARs) were calculated to study the optimization capability of these 3 modalities
      in the treatment of patients with NPC. The optimization time, delivery time,
      required monitor units (MUs), and delivery accuracy were also compared to
      investigate the feasibility of these 3 modalities. There was no significant
      difference (p = 0.92) in target coverage (TC) between WF-SIB IMRT (99.00 +/-
      0.79) and two-arc WF-SIB VMAT (97.98 +/- 1.29). However, both had higher TC than
      one-arc VMAT plans (89.92 +/- 6.32, p < 0.01). IMRT demonstrated the best
      protection of the spinal cord, whereas two-arc VMAT showed the minimum Dmax to
      OARs. No other significant differences were observed among these 3 modalities on
      CTV coverage and OAR sparing. The delivery and MU efficiency of one-arc and two
      arc WF-SIB VMAT were greatly improved compared with WF-SIB IMRT. The optimization
      time of one-arc and two-arc WF-SIB VMAT plans were 5 and 10 times greater than
      that of WF-SIB IMRT, respectively. The delivery accuracy of WF-SIB VMAT was not
      affected by the increased freedom. For patients with NPC, one-arc WF-SIB VMAT
      might not be able to achieve sufficient TC, whereas two-arc WF-SIB VMAT was able
      to achieve reasonable TC. No significant advantage on OAR protection was
      demonstrated by VMAT compared with IMRT. WF-SIB VMAT has significantly shorter
      delivery times, but WF-SIB IMRT may still be the first treatment choice for
      patients with NPC. 

PMID- 23973018
TI  - Hippocampal atrophy and memory dysfunction in patients with juvenile myoclonic
      epilepsy.
AB  - Juvenile myoclonic epilepsy (JME) is a well-defined idiopathic generalized
      epilepsy (IGE) syndrome, being the most common IGE in adults and accounting for 5
      11% of patients with epilepsy. While neuropsychological and neuroimaging studies
      have discussed the thalamofrontal dysfunction as the major pathophysiologic
      mechanism of JME, investigation on memory is scarce in patients with JME, with
      lack of objective assessments addressing common complaints and daily difficulties
      such as recalling telephone numbers, messages to pass on, and taking
      antiepileptic drugs regularly. The aim of this study was to objectively assess
      memory deficits in a group of patients with JME using neuropsychological
      examination combined with structural MRI of the hippocampi. After informed
      consent, a cohort of 56 consecutive patients with JME (29 males; mean age +/- SD
      = 26.5 +/- 9.01 years; range = 14.0-55.0 years) was included. The control group
      consisted of 42 healthy volunteers (18 males; mean age +/- SD = 31.0 +/- 8.54
      years; range=20.0-56.0 years) without a family history of neuropsychiatric
      disorders. Patients and controls were submitted to a MRI and to a
      neuropsychological assessment, and comparisons between groups were performed, as
      well as a correlation study between hippocampal atrophy and neuropsychological
      performance in a group of patients with JME. The level of statistical
      significance was set at p<0.05. Significant hippocampal atrophy among patients
      with JME was observed, which was correlated with memory dysfunctions. The present
      findings reinforce the existence of functional-anatomic ictogenic networks that
      are not limited to frontal lobes, providing further support towards the concept
      of 'system epilepsies' in JME.

PMID- 23973020
TI  - New device, same problem, no definitive answer.

PMID- 23973019
TI  - Acute combined revascularization in acute ischemic stroke with intracranial
      arterial occlusion: self-expanding solitaire stent during intravenous
      thrombolysis.
AB  - PURPOSE: To investigate the safety and efficacy of the self-expanding Solitaire
      stent used during intravenous thrombolysis (IVT) for intracranial arterial
      occlusion (IAO) in acute ischemic stroke (AIS). MATERIALS AND METHODS:
      Consecutive nonselected patients with AIS with IAO documented on computed
      tomographic angiography or magnetic resonance angiography and treated with IVT
      were included in this prospective study. Stent intervention was initiated and
      performed during administration of IVT without waiting for any clinical or
      radiologic signs of potential recanalization. Stroke severity was assessed by
      National Institutes of Health Stroke Scale (NIHSS), and 90-day clinical outcome
      was assessed by modified Rankin scale (mRS), with a good outcome defined as an
      mRS score of 0-2. Recanalization was rated by thrombolysis in cerebral infarction
      (TICI) scale. RESULTS: Fifty patients (mean age, 66.8 y +/- 14.6) had a baseline
      median NIHSS score of 18.0. Overall recanalization was achieved in 94% of
      patients, and complete recanalization (ie, TICI 3 flow) was achieved in 72% of
      patients. The mean time from stroke onset to maximal recanalization was 244.2
      minutes +/- 87.9, with a median of 232.5 minutes. The average number of device
      passes was 1.5, with a mean procedure time to maximal recanalization of 49.5
      minutes +/- 13.0. Symptomatic intracerebral hemorrhage occurred in 6% of
      patients. The median mRS score at 90 days was 1, and 60% of patients had a good
      outcome (ie, mRS score 0-2). The overall 3-month mortality rate was 14%.
      CONCLUSIONS: Combined revascularization with the Solitaire stent during IVT
      appears to be safe and effective in the treatment of acute IAO.

PMID- 23973021
TI  - The twisting maneuver for fluoroscopic-guided removal of nonpalpable tunneled
      central venous access catheter cuffs.
AB  - The present report describes an alternative technique for the detection of
      nonpalpable polyester cuffs during the removal of tunneled central venous
      catheters. By twisting the external segment of the tunneled catheter in obese
      patients or those with severe edema, fluoroscopy can easily confirm the estimated
      site of the hidden cuff. 

PMID- 23973022
TI  - Chest radiograph-based algorithm for managing malfunctioning ports.
AB  - PURPOSE: To evaluate a chest x-ray-based algorithm for managing malfunctioning
      ports. MATERIALS AND METHODS: A review of interventional radiology procedures on
      malfunctioning ports during the period 2000-2012 was performed. Events were
      divided into two periods: before and after implementation of an algorithm
      beginning with tip position evaluation using a chest x-ray. Time to return to
      usability, frequency of interventions to restore function, and frequency of
      malfunctioning ports remaining in use after the procedure were calculated.
      RESULTS: The review included 303 procedures before implementation of the
      algorithm on 237 access sites in 227 patients (mean age, 56 y; 38% male) and 155
      procedures after implementation of the algorithm on 131 access sites in 130
      patients (mean age, 55 y; 35% male). Implementation of the algorithm was
      associated with significantly fewer repeat checks on the same access (27% before
      algorithm, 9% after algorithm, P < .001) and reduced frequency of a
      malfunctioning port remaining in use after the interventional radiology procedure
      (43% before algorithm to 14% after algorithm, P < .001). Median time from
      consultation to revision was significantly less after implementing the algorithm
      (13 days before algorithm, 1 day after algorithm, P < .001). Median time from
      consultation to port usability was also less after implementing the algorithm
      (2.7 days before algorithm, 1 day after algorithm, P < .001). CONCLUSIONS:
      Implementation of the algorithm was associated with significantly less frequent
      repeat procedures on the same port and a lower frequency of malfunctioning ports
      remaining in place. Use of the algorithm was associated with significantly
      reduced time from consultation to revision and to return to usability. These
      findings suggest the algorithm allows triage of patients with malfunctioning
      ports to the appropriate intervention before undergoing a procedure.

PMID- 23973023
TI  - Removing the veil: price transparency in interventional radiology.

PMID- 23973024
TI  - CT angiogram of mesenteric anomaly.

PMID- 23973027
TI  - Successful percutaneous radiologic management of renal cell carcinoma tumor
      seeding caused by percutaneous biopsy performed before ablation.
AB  - A case is reported of the successful image-based detection, diagnosis, and
      percutaneous ablation of tumor seeding in a 61-year-old man that was caused by
      percutaneous biopsy of a renal cell carcinoma performed before cryoablation and
      was not detected until 4 years after the biopsy procedure. Although tumor seeding
      is a rare complication after percutaneous biopsy or ablation, this case
      emphasizes the importance of imaging surveillance of the needle tract used during
      both biopsy and ablation procedures, provides guidance on measures that can be
      used to minimize the occurrence of tumor seeding, and demonstrates that entirely
      radiologic management can be successful. 

PMID- 23973026
TI  - Successful treatment of endoscopically unmanageable rectal varices by balloon
      occluded antegrade transvenous sclerotherapy followed by microcoil embolization.
AB  - The present report describes two cases of endoscopically unmanageable rectal
      varices that were treated by balloon-occluded antegrade transvenous sclerotherapy
      (BATS) followed by microcoil embolization. Follow-up endoscopy confirmed
      eradication of the rectal varices. Balloon-occluded rectal venography showed
      stasis of contrast material and sclerosing agent for 30 minutes in both cases of
      rectal varices, which indicated that the inflow vessel was a single dilated
      superior rectal vein without other minor inflow vessels. BATS appears to be a
      feasible therapeutic option for the treatment of rectal varices of this
      hemodynamic type. 

PMID- 23973028
TI  - Successful endovascular treatment of iliac arteriovesical fistula with secondary
      stent-graft infection.
AB  - A 58-year-old woman initially presented with massive gross hematuria and iliac
      arteriovesical fistula (IAVF). Endovascular stent-graft repair achieved complete
      exclusion of the IAVF and controlled the bleeding, but sepsis subsequently
      developed because of endograft infection. Endovascular embolization of the
      infected stent graft was performed after extraanatomic bypass surgery. The
      patient recovered and showed no signs of graft infection or recurrent
      fistulization at 14 months after treatment. Endovascular embolization of infected
      stent grafts combined with extraanatomic bypass may be an acceptable treatment
      option for graft-related sepsis in cases that are resistant to conservative
      treatment and pose high surgical risk for graft excision. 

PMID- 23973029
TI  - Using wire markers to identify vulnerable skin during fluoroscopy.

PMID- 23973030
TI  - Two cases of femoral arterial access through a previously placed StarClose clip.

PMID- 23973031
TI  - Ultrasound-guided paravertebral block for management of abdominal pain after
      transarterial embolization using drug-eluting beads loaded with irinotecan.

PMID- 23973032
TI  - Rare instance of small bowel obstruction following unilateral uterine artery
      embolization.

PMID- 23973033
TI  - Removal of a TrapEase inferior vena cava filter for chronic abdominal pain 2
      years after implantation.

PMID- 23973034
TI  - Recurrent retrograde intussusception after roux-en-Y gastric bypass:
      intussusception reduction by the transhepatic approach.

PMID- 23973035
TI  - Inadvertent esophageal stent deployment into a false passage with subsequent
      endoscopic retrieval.

PMID- 23973036
TI  - Acute coronary syndromes, seedless watermelons, and colchicine.

PMID- 23973037
TI  - Acute coronary syndromes: much progress, new challenges.

PMID- 23973038
TI  - Pros, cons, and organization of prehospital thrombolysis.
AB  - BACKGROUND: Early initiation of reperfusion therapy in ST-segment elevation
      myocardial infarction improves outcome. Prehospital thrombolysis (PHT) is 1
      strategy to deliver earlier reperfusion. OBJECTIVE: The goal of this study was to
      discuss the pros and cons of PHT and to describe the implementation of a program
      of PHT in the Hunter Region of Australia. METHODS: Recent literature on PHT was
      reviewed to present a critical assessment of the evidence to support PHT.
      Different models of PHT are presented including the experience of the
      introduction of the Hunter program. RESULTS: Meta-analyses of clinical trials and
      registries have shown that PHT significantly decreases the time to thrombolysis,
      with reduction in the incidence of cardiogenic shock and a trend to a mortality
      benefit. The STREAM study reinforces current policy, which favors primary
      percutaneous coronary intervention (PCI) over thrombolysis, providing that PCI
      can be performed within an appropriate time interval; emphasizes that timely
      thrombolysis linked to an early invasive strategy provides an equivalent outcome
      when timely primary PCI is not possible; and supports other published experience
      that early-rescue PCI can be performed safely after administration of PHT.
      Although PHT can be implemented by trained paramedics working with on-board
      physicians, the Hunter Region has successfully used paramedics and ECG telemetry
      in consultation with hospital-based physicians. When the time to open the artery
      is <=90 minutes, primary PCI is preferred. When the time to open the artery is
      >90 minutes, PHT with immediate transport postthrombolysis to a PCI-capable
      hospital is feasible and effective. CONCLUSIONS: PHT delivered by trained
      paramedics with telemetery backup to assist ECG interpretation is feasible and
      delivers the prospect of early reperfusion.

PMID- 23973039
TI  - New antiplatelet agents and the role of platelet function testing in acute
      coronary syndromes.
AB  - BACKGROUND: Dual antiplatelet therapy is a guideline mandated for patients with
      acute coronary syndromes (ACS). Despite its use, thrombotic events continue to
      occur both early and late. Platelet function testing has been used to define the
      in vitro effects of new antiplatelet agents, and it has been suggested that it be
      used to choose therapy. The role of platelet function testing, particularly with
      newer antiplatelet agents, remains unclear. OBJECTIVE: We review the rationale
      for platelet function testing and its application in monitoring patients on
      antiplatelet therapy. We also review recent clinical trials of newer antiplatelet
      agents. On the basis of this review, we reach conclusions on the current role of
      antiplatelet function testing in monitoring modern antiplatelet therapy and the
      role of the new antiplatelet agents in the treatment of ACS. METHODS: We reviewed
      recent publications on platelet function testing and clinical trials of newer
      antiplatelet therapies compared with clopidogrel. RESULTS: Platelet function
      testing is complex, but there is now a bedside test, VerifyNow. High platelet
      reactivity has been associated with worse cardiovascular outcomes in patients
      undergoing percutaneous coronary intervention. Recent clinical trials have not
      found any advantage in outcomes in patients who have their therapy adjusted by
      monitoring their platelet function. Newer agents, prasugrel, ticagrelor, and
      cangrelor, produce more rapid, complete, less variable effects on platelet
      function than clopidogrel. Prasugrel was found to improve outcomes compared with
      clopidogrel in patients with ACS undergoing percutaneous intervention. Ticagrelor
      is beneficial in all patients with ACS and reduces cardiovascular mortality
      compared with clopidogrel. Cangrelor improves outcomes in patients undergoing
      stenting. Recent studies to assess the role of platelet function monitoring of
      the effects of clopidogrel and modifying treatments have not been successful.
      CONCLUSION: Recent clinical trials have indicated that newer antiplatelet agents
      have advantages over clopidogrel in the treatment of ACS. Platelet function
      testing gives us a guide to the timing, efficacy, and variability of therapy and
      can correlate with poor patient outcomes; however, the use of antiplatelet
      function testing to tailor therapy does not seem appropriate.

PMID- 23973040
TI  - Management of acute coronary syndromes in patients with diabetes: implications of
      the FREEDOM trial.
AB  - BACKGROUND: Diabetes mellitus (DM) is a powerful independent risk factor for
      multivessel, diffuse coronary artery disease (CAD). The optimal coronary
      revascularization strategy in DM is not clearly defined, but past trials have
      suggested an advantage for coronary artery bypass grafting (CABG). Recently, the
      Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal
      Management of Multivessel Disease (FREEDOM) trial found patients randomized to
      CABG had lower rates of death and myocardial infarction (MI) compared with those
      randomized to percutaneous coronary intervention (PCI). OBJECTIVE: This article
      reviews the contemporary management of patients with DM presenting with acute
      coronary syndromes, particularly ST-elevation MI, in the post-FREEDOM era.
      METHODS: We undertook a comprehensive review of published literature addressing
      trials in this field performed to address current knowledge both in the pre- and
      post-FREEDOM era. RESULTS: The implications of FREEDOM for patients with acute
      coronary syndrome are that CABG provides a significant benefit, compared with PCI
      with drug-eluting stents, to patients with DM and multivessel coronary artery
      disease; and that patients similar to those enrolled in FREEDOM should receive
      CABG in preference to PCI. The relevance of FREEDOM's findings to the large
      proportion of patients who would not meet inclusion criteria-including patients
      with an acute coronary syndrome undergoing an early or emergent invasive
      strategy, remains uncertain. DISCUSSION: FREEDOM's outcomes have generated
      uncertainty regarding best practice once thrombolysis in myocardial infarction
      grade 3 flow is re-established in patients with DM and multivessel disease.
      Current interventional guidelines recommend optimally treating the culprit
      artery; however, decisions made at the time of revascularization influence future
      revascularization strategies, particularly stent choice and resultant P2Y12
      receptor antagonist therapy. The preferred method for future revascularization
      may be questioned if the patient's residual coronary stenoses do not, post-PCI,
      meet the FREEDOM inclusion criteria, or where the left anterior descending artery
      is the infarct-related artery, and after left anterior descending artery PCI the
      patient would not receive an internal mammary graft. The management of residual
      disease and the preferred (further) revascularization strategy needs to be tested
      in an appropriately powered randomized trial. CONCLUSIONS: The optimal
      revascularization strategy in patients with acute coronary syndrome, diabetes,
      and multivessel disease, in particular those with ST elevation, is unclear, and
      not guided by level A (or B) evidence. Currently CABG is favored over PCI, and an
      individually tailored, collaborative approach, guided by a multidisciplinary
      heart team, should be employed.

PMID- 23973041
TI  - Improving outcomes after acute coronary syndrome with rehabilitation and
      secondary prevention.
AB  - BACKGROUND: International studies suggest almost half of all major coronary
      episodes annually occur in survivors of acute coronary syndrome (ACS). OBJECTIVE:
      A greater focus on medium- and long-term ACS management and adherence to proven
      therapies is essential if out-of-hospital reductions in mortality and morbidity
      are to be optimized. METHODS: A national panel of clinical and research opinion
      leaders in ACS care met for 2 days to set future priorities in health care
      delivery. RESULTS: Lifestyle, control of risk factors, and prescription of
      pharmacological therapies can improve the course of coronary heart disease (CHD)
      by reducing all-cause and cardiovascular mortality by 15% to 25%. All ACS
      patients stand to benefit from rehabilitation and systematic secondary
      prevention, however, underutilization and suboptimal adherence to rehabilitation
      and secondary prevention measures persist globally. RESULTS: A range of new
      initiatives in Australia and elsewhere indicate that time is ripe for change to
      improve the uptake of preventative treatments in patients after ACS. Key
      universal drivers of delivering best evidence practice for medium- to long-term
      care after ACS are economics and locality. CONCLUSIONS: Health-service redesign
      involving all stakeholders will be integral to increasing access, uptake, and
      adherence to lifestyle, control of risk factors, and pharmacologic therapies
      shown to improve cardiovascular outcomes.

PMID- 23973042
TI  - Targeting the unstable plaque in acute coronary syndromes.
AB  - BACKGROUND: Rupture or erosion of an unstable atherosclerotic plaque is the
      typical pathology and usual cause of acute coronary syndromes. Despite detailed
      understanding of the processes of lipid accumulation, thinning of the fibrous
      cap, and inflammation leading to plaque instability, there are no strategies in
      clinical use that uniquely target the unstable plaque. OBJECTIVE: A critical
      review of recent publications on potential therapies that could be used to
      stabilize unstable plaque. METHODS: We searched PubMed, other literature
      databases, drug development sites, and clinical trial registries to retrieve
      clinical studies on anti-inflammatory and lipid-modulating therapies that could
      be used to stabilize unstable atherosclerotic plaque. RESULTS: Multiple
      experimental targets involving lipid and inflammatory pathways have the potential
      to stabilize the plaque and expand the armamentarium against coronary artery
      disease. Randomized clinical trials of darapladib, methotrexate, canakinumab, and
      colchicine are well advanced to establish if plaque stabilization is feasible and
      effective in patients with acute coronary syndromes. CONCLUSIONS: Although there
      are still no agents in clinical use for plaque stabilization, there are important
      advances in understanding plaque instability and several encouraging approaches
      are being evaluated in Phase III clinical trials.

PMID- 23973043
TI  - Dehydrated stomatocytic anemia due to the heterozygous mutation R2456H in the
      mechanosensitive cation channel PIEZO1: a case report.

PMID- 23973044
TI  - Change in demographic pattern of dengue virus infection: evidence from 2011
      dengue outbreak in Punjab, Pakistan.

PMID- 23973045
TI  - Equity of uptake of a diabetic retinopathy screening programme in a
      geographically and socio-economically diverse population.
AB  - OBJECTIVES: At the time of undertaking the audit, the uptake of diabetic
      retinopathy screening in Derbyshire was 73%, below the national standard of 80%.
      To assess equity of access to diabetic retinopathy screening in a geographically
      and ethnically diverse population and determine predictors for poor uptake that
      will inform service improvements. STUDY DESIGN: Mixed methods health equity
      audit. METHODS: Postal questionnaires were issued to 1000 people invited for
      diabetic retinopathy screening in May 2010 and telephone interviews were
      conducted with subsample of 32 people who had not made a screening appointment.
      Routine data from the screening programme was used to identify characteristics of
      people who did not respond to screening invitation. The adjusted odds ratios (OR)
      and 95% confidence intervals (95% CI) using multivariate methods were calculated
      in this study. RESULTS: The response rate to the postal questionnaire was 43%. Of
      these, 28% of respondents did not recall discussing the importance of diabetic
      retinopathy screening with their primary care team and 11% of people did not
      understand the term 'diabetic retinopathy'. Non-uptake of screening was
      associated with deprivation (OR 1.19, 95% CI 1.10-1.29 for those living in the
      most deprived areas compared to the least deprived) and young people were over
      three times more likely not to participate than older people (OR 3.13, 95% CI
      2.70-3.64 for men under 40 compared to men over 80 and OR 3.03, 95% CI 1.54-5.98
      for people with type 1 diabetes under 40 compared to those over 80). CONCLUSIONS:
      Ensuring that primary care and other health care and third sector organisations
      convey the importance of diabetic retinopathy screening with patients and
      improving patients' understanding of the screening programme may improve uptake.
      Interventions to increase uptake should be targeted to younger people, especially
      those with type 1 diabetes and people living in more deprived areas.

PMID- 23973046
TI  - Fractionated stereotactic radiotherapy for acoustic neuromas: long-term outcomes.
AB  - AIMS: Acoustic neuromas are rare, benign intracranial tumours. There are a
      variety of treatment options, with no clear optimal management strategy and wide
      variation in treated outcomes. We report the outcomes from a 15 year cohort of
      patients treated at our centre using fractionated stereotactic radiotherapy (52.5
      Gy in 25 fractions). MATERIALS AND METHODS: We analysed a retrospective case
      series. Patients were identified from patient records and a retrospective review
      of case notes and imaging reports was undertaken. We assessed tumour response
      using RECIST criteria and recorded toxicity. Progression-free survival was
      estimated using the Kaplan-Meier method. The study was conducted according to the
      STROBE guidelines. RESULTS: In total, 93 patients were identified; 83 patients
      had follow-up data, with a median follow-up period of 5.7 years. The overall
      control rate using RECIST criteria was 92%. Data on complications were available
      for 90 patients, with six (7%) experiencing a reduction in hearing, one (1%)
      developing trigeminal nerve dysfunction and one (1%) a deterioration in facial
      nerve function. Other toxicities included four (4%) patients who developed
      hydrocephalus, requiring the placement of a shunt and one (1%) patient who
      developed radiation brainstem necrosis. After further evaluation this patient was
      deemed to have been treated within acceptable dose constraints. CONCLUSION: These
      data suggest that a good control rate of acoustic neuromas is achievable using
      fractionated stereotactic radiotherapy to a dose of 52.5 Gy in 25 fractions.
      Toxicity is considered acceptable but the episode of radiation brainstem necrosis
      remains of concern and is the subject of further work.

PMID- 23973047
TI  - Short- and long-term changes of condylar position after bilateral sagittal split
      ramus osteotomy for mandibular advancement in combination with Le Fort I
      osteotomy evaluated by cone-beam computed tomography.
AB  - PURPOSE: Bilateral sagittal split ramus osteotomy (BSSO) may change condylar
      position, which can be one of the factors contributing to skeletal relapse. This
      study evaluated short- and long-term changes in condylar position using cone-beam
      computed tomography (CBCT) and investigated changes in temporomandibular joint
      (TMJ) signs after BSSO for mandibular advancement in combination with Le Fort I
      osteotomy. MATERIALS AND METHODS: Thirty-one patients were included, and CBCT
      data of 62 TMJs were collected before surgery (T0), immediately after surgery
      (T1), 3 months after surgery (T2), and at the last follow-up at 12.1 +/- 3.0
      months after surgery (T3). The relation of the condyle to the fossa was evaluated
      by the method of Pullinger and Hollender (Oral Surg Oral Med Oral Pathol 62:719,
      1986). Clinical examination, with a special focus on signs of temporomandibular
      disorder (TMD), was documented at T0, T2, and T3. Repeated-measures analysis of
      variance (P = .05) and chi2 test (P = .05) were performed. RESULTS: Data of 27
      patients were used for statistical analysis. Values from the formula of Pullinger
      and Hollender changed significantly with time, but there was no significant
      difference between the right and left condyles. Condyles moved inferoposteriorly
      immediately after surgery (T0 to T1) followed by anterosuperior movement 3 months
      after surgery (T1 to T2). The superimposed effect showed posterosuperior movement
      compared with the initial position before surgery (T0 to T2) and this position
      remained stable at 1-year follow-up (T2 to T3). A decrease of TMD signs over
      time, from 22.6% (T0) to 12.9% (T2) and 9.7% (T3), was observed, which showed no
      statistical significance. CONCLUSIONS: There were obvious changes in condylar
      position after BSSO in combination with Le Fort I osteotomy. Condyles tended to
      be located in a concentric position in relation to the glenoid fossa 3 months
      after surgery and remained stable during the 1-year follow-up. These changes did
      not cause an increase of TMD signs.

PMID- 23973048
TI  - Marsupialization facilitates eruption of dentigerous cyst-associated mandibular
      premolars in preadolescent patients.
AB  - PURPOSE: The purpose of the present study was to investigate the eruption of
      dentigerous cyst (DC)-associated mandibular premolars after marsupialization in
      preadolescents. PATIENTS AND METHODS: The present study was a retrospective
      cohort study of preadolescent patients with DCs who were treated as outpatients
      at the Department of Oral and Maxillofacial Surgery, Ninth People's Hospital,
      Shanghai Jiao Tong University School of Medicine. For our study, the data from
      these patients were collected, and the eruption of the premolar teeth, along with
      related factors, such as the interval to eruption, cusp depth, angulation, cyst
      size, and eruption space, were analyzed for the cyst group compared with the
      noncyst control group. RESULTS: The mean age of the patients was 9.1 years. All
      teeth associated with DCs erupted successfully after marsupialization. The follow
      up panoramic radiograph showed that the cysts had disappeared and had been
      replaced by regenerated bone. The initial panoramic radiograph showed the
      angulation of the teeth in the cyst group had a significantly larger inclination
      angle than did the teeth in the noncyst group (P < .05). However, no significant
      difference was found for cusp depth, root formation, or space measurement. The
      gender, age, cusp depth, angulation, and eruption space were not factors
      influencing the eruption of the DC-associated tooth for preadolescent patients in
      the present study. In addition, the cyst-associated teeth took less time to erupt
      than the teeth in the control group. CONCLUSIONS: The results of the present
      study suggest that DC-associated mandibular premolars can erupt spontaneously
      after marsupialization in preadolescents.

PMID- 23973049
TI  - Menopause and work: an electronic survey of employees' attitudes in the UK.
AB  - OBJECTIVES: This study explored women's experiences of working through menopausal
      transition in the UK. It aimed to identify the perceived effects of menopausal
      symptoms on working life, to outline the perceived effects of work on menopausal
      symptoms, and to provide recommendations for women, healthcare practitioners and
      employers. METHODS: An electronic questionnaire was distributed to women aged 45
      55 in professional, managerial and administrative (non-manual) occupations in 10
      organisations. Items included: age, age and gender of line manager, educational
      level, job satisfaction; menopausal status; symptoms that were problematic for
      work; hot flushes; working conditions; work performance, disclosure to line
      managers; individual coping strategies; and, effective workplace adjustments and
      employer support. RESULTS: The final sample comprised 896 women. Menopausal
      transition caused difficulties for some women at work. The most problematic
      symptoms were: poor concentration, tiredness, poor memory, feeling low/depressed
      and lowered confidence. Hot flushes were particularly difficult. Some women felt
      work performance had been negatively affected. The majority of women were
      unwilling to disclose menopause-related health problems to line managers, most of
      whom were men or younger than them. Individual coping strategies were described.
      Four major areas for organisational-level support emerged: (i) greater awareness
      among managers about menopause as a possible occupational health issue, (ii)
      flexible working hours, (iii) access to information and sources of support at
      work, and (iv) attention to workplace temperature and ventilation. CONCLUSION:
      Employers and healthcare practitioners should be aware that menopausal transition
      causes difficulty for some women at work, and that much can be done to support
      them.

PMID- 23973051
TI  - Long-term culture of primary porcine oviduct epithelial cells: validation of a
      comprehensive in vitro model for reproductive science.
AB  - Recently, we established a protocol for the cultivation of primary porcine
      oviduct epithelial cells (POEC), which promoted tissue-like morphology for a
      prolonged culture period. The present study focuses on developing this model into
      a comprehensive, standardized culture system, as a candidate tool for
      reproductive toxicity testing and basic research. We cultivated POEC isolated
      from 25 animals in our culture system for both 3 and 6 weeks and systematically
      analyzed effects of medium conditioning, supplementation with standardized sera,
      and culture duration in both freshly isolated and cryopreserved cells. The
      differentiation status was evaluated via histomorphometry, transepithelial
      electrical resistance (TEER) measurement, and expression analyses. The culture
      system possessed high reproducibility, more than 95% of cultures achieved a fully
      differentiated phenotype. Cells recapitulated in vivo-like morphology and
      ultrastructure from 3 to 6 weeks. Cryopreservation of the cells prior to
      cultivation did not affect culture quality of POEC. Employment of conditioned
      medium ensured optimal promotion of POEC differentiation, and different
      standardized sera induced fully differentiated phenotypes. Consistent TEER
      establishment indicated the presence and maintenance of cell type-specific
      intercellular junctions. The functionality of POEC was proven by consistent mucin
      secretion and stable expression of selected markers over the whole culture
      duration. We conclude that POEC are suitable for experiments from 3 weeks up to
      at least 6 weeks of culture. Therefore, this culture system could be used for in
      vitro estrous cycle simulation and long-term investigation of toxic effects on
      oviduct epithelium.

PMID- 23973050
TI  - Distribution of caprine arthritis encephalitis virus provirus, RNA, and antigen
      in the reproductive tract of one naturally and seven experimentally infected
      bucks.
AB  - Caprine arthritis encephalitis is a worldwide, multisystemic disease caused by a
      small ruminant lentivirus. Although the main route of transmission is oral,
      detection of proviral DNA of the caprine arthritis encephalitis virus (CAEV) in
      caprine semen has been previously described. However, the presence of viral
      antigens in the male reproductive tract has apparently never been reported. The
      objective was to study lesions in the buck reproductive system and to detect, in
      these tissues, the presence of proviral DNA, viral RNA and CAEV antigens. Tissues
      from eight CAEV-infected bucks (one naturally and seven experimentally infected)
      were analyzed by histopathology, nested polymerase chain reaction, reverse
      transcriptase-polymerase chain reaction, and immunohistochemistry. Interstitial
      pneumonia, synovitis, and lesions in the male reproductive tract were detected in
      some of the bucks. Proviral DNA was detected in the lungs and joints as well as
      in the reproductive systems of all animals, whereas viral RNA was detected only
      in the genital tract of the naturally infected buck. Viral antigens were
      immunostained in most of the organs of the male reproductive tract. This report
      was apparently the first to clearly demonstrate CAEV antigen expression in the
      male reproductive tract, which indicates the possibility of venereal transmission
      of CAEV.

PMID- 23973052
TI  - Biodegradation and flushing of MBT wastes.
AB  - Mechanical-biological treatment (MBT) processes are increasingly being adopted as
      a means of diverting biodegradable municipal waste (BMW) from landfill, for
      example to comply with the EU Landfill Directive. However, there is considerable
      uncertainty concerning the residual pollution potential of such wastes. This
      paper presents the results of laboratory experiments on two different MBT waste
      residues, carried out to investigate the remaining potential for the generation
      of greenhouse gases and the flushing of contaminants from these materials when
      landfilled. The potential for gas generation was found to be between 8% and 20%
      of that for raw MSW. Pretreatment of the waste reduced the potential for the
      release of organic carbon, ammoniacal nitrogen, and heavy metal contents into the
      leachate; and reduced the residual carbon remaining in the waste after final
      degradation from ~320g/kg dry matter for raw MSW to between 183 and 195g/kg dry
      matter for the MBT wastes. 

PMID- 23973062
TI  - Site-specific fluorescent labeling of tubulin.
AB  - Fluorescent tubulin can be prepared in which a fluorophore is covalently bound to
      the protein at only the carboxy terminus of the alpha-subunit of the alphabeta
      tubulin dimer. This two-step procedure consists of an enzymatic reaction followed
      by a bioorthogonal chemical reaction. In the first step of the process, the
      enzyme tubulin tyrosine ligase is used to attach a reactive tyrosine derivative,
      3-formyltyrosine, to the protein. In the second step of the procedure, a
      fluorophore possessing a complementary reactive functional group, such as a
      hydrazine, hydrazide, or hydroxylamine, is allowed to react with the protein
      under conditions that are compatible with native tubulin. Polymerization
      competent, fluorescently labeled tubulin can be prepared in just a few hours
      using this protocol. The method described here should be useful for attaching
      virtually any probe or material to tubulin at this site.

PMID- 23973063
TI  - Measuring microtubule persistence length using a microtubule gliding assay.
AB  - The mechanical properties of microtubules have been an area of active research
      for the past two decades, in part because understanding the mechanics of
      individual microtubules contributes to modeling whole-cell rigidity and structure
      and hence to better understanding the processes underlying motility and
      transport. Moreover, the role of microtubule structure and microtubule-associated
      proteins (MAPs) in microtubule stiffness remains unclear. In this chapter, we
      present a kinesin-driven microtubule gliding assay analysis of persistence length
      that is amenable to simultaneous variation of microtubule parameters such as
      length, structure, or MAP coverage and determination of persistence length. By
      combining sparse fluorescent labeling of individual microtubules with single
      particle tracking of individual fluorophores, microtubule gliding trajectories
      are tracked with nanometer-level precision. The fluctuations in these
      trajectories, due to thermal fluctuations in the microtubules themselves, are
      analyzed to extract the microtubule persistence length. In the following, we
      describe this gliding assay and analysis and discuss two example microtubule
      variables, length and diameter, in anticipation that the method may be of wide
      use for in vitro study of microtubule mechanical properties. 

PMID- 23973064
TI  - Structural studies of the doublecortin family of MAPs.
AB  - Doublecortin (DCX) is a microtubule (MT)-stabilizing protein essential for
      neuronal migration during human brain development. Missense mutations in DCX
      cause severe brain defects. This implies that the many other MT-stabilizing
      proteins in neurons cannot compensate for DCX function. To understand the unusual
      properties of DCX, we expressed the recombinant human DCX in Sf9 cells and
      undertook structural characterization of its interaction with MTs using cryo
      electron microscopy. DCX specifically nucleates 13-protofilament (13-pf) MTs, the
      architecture of human MTs in vivo. Cryo-electron tomography (cryo-ET) of DCX
      nucleated MTs showed that they are primarily built from B-lattice contacts
      interrupted by a single discontinuity, the seam. Because of this asymmetry, we
      used single-particle reconstruction and determined the 8A structure of DCX
      stabilized 13-pf MTs in the absence of a stabilizing drug. The DCX-binding site,
      at the corner of four tubulin dimers, is ideally suited to stabilize both lateral
      and longitudinal tubulin lattice contacts. Its precise geometry suggests that DCX
      is sensitive to the angle between pfs, and thereby provides insight into the
      specificity of DCX for 13-pf MT architecture. DCX's precise interaction at the
      corner of four tubulin dimers also means that DCX does not bind the MT seam. Our
      work has provided mechanistic insight into the evolutionarily conserved DCX
      family of MT-stabilizing proteins and also into more general regulatory
      mechanisms of the MT cytoskeleton.

PMID- 23973065
TI  - Detection and quantification of microtubule detachment from centrosomes and
      spindle poles.
AB  - Microtubule detachment from microtubule organizing centers is an important
      cellular process required for normal cell proliferation. When cells enter
      mitosis, microtubule turnover increases along with a concurrent increase in
      microtubule detachment. MCAK, a kinesin-related protein whose abundance is
      highest during the early stages of mitosis, has been shown to regulate
      microtubule detachment. Abnormal increases or decreases in the frequency of
      detachment interfere with spindle function and inhibit cell division. It has been
      shown that drugs able to promote microtubule assembly (e.g., paclitaxel,
      epothilones) prevent cell division by suppressing microtubule detachment from
      centrosomes. Conversely, cytotoxic concentrations of microtubule destabilizing
      drugs (e.g., vinblastine, nocodazole), tubulin mutations that cause paclitaxel
      resistance, and specific beta-tubulin isotypes increase the frequency of
      microtubule detachment. In this chapter, we describe a method to calculate the
      frequency of microtubule detachment by transfecting cells with EGFP-MAP4 and
      directly observing detachment by live cell imaging. 

PMID- 23973066
TI  - Regulation of tubulin expression by micro-RNAs: implications for drug resistance.
AB  - In this chapter, we provide an overview of methods for studying micro-RNA
      regulation of tubulin isotypes. In clinical studies, beta-tubulin isotypes were
      found to be biomarkers for tumor formation. In addition, because changes in the
      levels of specific beta-tubulin isotypes alter the stability of microtubules in
      mitotic spindles in vitro, it has been hypothesized that changes in microtubule
      protein levels could contribute to chemotherapy resistance. Over the past 15
      years, micro-RNAs have been shown to target mRNAs in signaling pathways involved
      in tumor suppression, as well as tumorigenesis. Investigating micro-RNA
      regulation of tubulin isotypes will shed light on the mechanisms underlying the
      processes that implicate tubulin isotypes as biomarkers for aggressive tumors or
      chemotherapy resistance. The methods discussed in this chapter include the use of
      micro-RNA superarrays, next-generation sequencing, real-time PCR experiments,
      upregulation of micro-RNAs, and immunoprecipitation of RNA-induced silencing
      complex. We will show examples of data collected using these methods and how
      these data contribute to understanding paclitaxel resistance. 

PMID- 23973067
TI  - Determining the structure-mechanics relationships of dense microtubule networks
      with confocal microscopy and magnetic tweezers-based microrheology.
AB  - The microtubule (MT) cytoskeleton is essential in maintaining the shape,
      strength, and organization of cells. Its spatiotemporal organization is
      fundamental for numerous dynamic biological processes, and mechanical stress
      within the MT cytoskeleton provides an important signaling mechanism in mitosis
      and neural development. This raises important questions about the relationships
      between structure and mechanics in complex MT structures. In vitro, reconstituted
      cytoskeletal networks provide a minimal model of cell mechanics while also
      providing a testing ground for the fundamental polymer physics of stiff polymer
      gels. Here, we describe our development and implementation of a broad tool kit to
      study structure-mechanics relationships in reconstituted MT networks, including
      protocols for the assembly of entangled and cross-linked MT networks,
      fluorescence imaging, microstructure characterization, construction and
      calibration of magnetic tweezers devices, and mechanical data collection and
      analysis. In particular, we present the design and assembly of three neodymium
      iron boron (NdFeB)-based magnetic tweezers devices optimized for use with MT
      networks: (1) high-force magnetic tweezers devices that enable the application of
      nano-Newton forces and possible meso- to macroscale materials characterization;
      (2) ring-shaped NdFeB-based magnetic tweezers devices that enable oscillatory
      microrheology measurements; and (3) portable magnetic tweezers devices that
      enable direct visualization of microscale deformation in soft materials under
      applied force.

PMID- 23973068
TI  - Studying mitochondria and microtubule localization and dynamics in standardized
      cell shapes.
AB  - Mammalian cells show a large diversity in shape and are both shape-changing and
      mobile when cultured on conventional uniform substrates. The use of
      micropatterning techniques limits the number of variable parameters, by imposing
      shape and standardized adhesive areas on the cells, which facilitates analysis.
      By changing size or shape of the micropattern, for example, forcing a polar axis
      on the cell, it is possible to study how these parameters impact organelle
      organization, distribution, and dynamics inside the cell. To study the
      mitochondrial network, which is composed of dynamic tubular organelles dependent
      on the microtubule cytoskeleton for its distribution, it is important to be able
      to distinguish between distinct mitochondria. Here, we present a practical method
      with which we spread the cells on large patterns created with deep UV technique,
      which not only makes the cells uniform in size and shape as well as immobile, and
      therefore easier to compare and analyze, but also expands the mitochondrial
      network and allows for an easier tracking of appropriately labeled individual
      mitochondria. 

PMID- 23973069
TI  - Going solo: measuring the motions of microtubules with an in vitro assay for TIRF
      microscopy.
AB  - Microtubule (MT) plus-end-tracking proteins (+TIPs) specifically associate with
      the plus ends of growing MTs, thereby determining, in many different ways, the
      dynamic behavior of the MTs. Over the past years, a variety of fluorescently
      tagged +TIPs have been purified. Their reconstitution together with other
      purified components involved in MT plus-end-tracking, and analysis by total
      internal reflection fluorescence microscopy, has helped to elucidate some of the
      crucial mechanisms underlying the motion of MTs. For example, +TIP dwell time and
      association rate, and key MT dynamic instability parameters can be measured in a
      controlled cell-free environment. In this chapter, we have aimed to describe in
      an accessible and practical manner how we carry out these assays in our lab. We
      cover basic steps such as the preparation of glass and sample chambers through to
      the details of the in vitro +TIP assay. When appropriate, we mention common
      problems providing practical help to overcome potential issues. 

PMID- 23973070
TI  - Analysis of microtubules in isolated axoplasm from the squid giant axon.
AB  - Biochemical specialization of cellular microtubules has emerged as a primary
      mechanism in specifying microtubule dynamics and function. However, study of
      specific subcellular populations of cytoplasmic microtubules has been limited,
      particularly in the nervous system. The complexity of nervous tissue makes it
      difficult to distinguish neuronal microtubules from glial microtubules, and
      axonal microtubules from dendritic and cell body microtubules. The problem is
      further compounded by the finding that a large fraction of neuronal tubulin is
      lost during standard preparations of brain tubulin, and this population of stable
      microtubules is enriched in axons. Here, we consider a unique biological model
      that provides a unique opportunity to study axonal microtubules both in situ and
      in vitro: isolated axoplasm from the squid giant axon. The axoplasm model
      represents a powerful system for addressing fundamental questions of microtubule
      structure and function in the axon. 

PMID- 23973071
TI  - Imaging GTP-bound tubulin: from cellular to in vitro assembled microtubules.
AB  - Microtubules display a very dynamic behavior, and the presence of the guanosine
      triphosphate (GTP) cap at the plus ends of microtubules is essential to regulate
      microtubule dynamics. Dimitrov et al. (2008) showed that GTP-tubulin is present
      not only at the plus ends but also in discrete locations along the microtubule
      lattice. These GTP islands were proposed to contribute to rescue events. Studying
      the localization of GTP-tubulin in microtubules is essential to better comprehend
      some core aspects in the regulation of microtubule dynamics. In this chapter, we
      recapitulate essential tools to study the GTP-tubulin using the recombinant
      antibody MB11 from permeabilized cells to in vitro assays.

PMID- 23973072
TI  - Tubulin-specific chaperones: components of a molecular machine that assembles the
      alpha/beta heterodimer.
AB  - The tubulin heterodimer consists of one alpha- and one beta-tubulin polypeptide.
      Neither protein can partition to the native state or assemble into polymerization
      competent heterodimers without the concerted action of a series of chaperone
      proteins including five tubulin-specific chaperones (TBCs) termed TBCA-TBCE. TBCA
      and TBCB bind to and stabilize newly synthesized quasi-native beta- and alpha
      tubulin polypeptides, respectively, following their generation via multiple
      rounds of ATP-dependent interaction with the cytosolic chaperonin. There is free
      exchange of beta-tubulin between TBCA and TBCD, and of alpha-tubulin between TBCB
      and TBCE, resulting in the formation of TBCD/beta and TBCE/alpha, respectively.
      The latter two complexes interact, forming a supercomplex (TBCE/alpha/TBCD/beta).
      Discharge of the native alpha/beta heterodimer occurs via interaction of the
      supercomplex with TBCC, which results in the triggering of TBC-bound beta-tubulin
      (E-site) GTP hydrolysis. This reaction acts as a switch for disassembly of the
      supercomplex and the release of E-site GDP-bound heterodimer, which becomes
      polymerization competent following spontaneous exchange with GTP. The tubulin
      specific chaperones thus function together as a tubulin assembly machine,
      marrying the alpha- and beta-tubulin subunits into a tightly associated
      heterodimer. The existence of this evolutionarily conserved pathway explains why
      it has never proved possible to isolate alpha- or beta-tubulin as stable
      independent entities in the absence of their cognate partners, and implies that
      each exists and is maintained in the heterodimer in a nonminimal energy state.
      Here, we describe methods for the purification of recombinant TBCs as
      biologically active proteins following their expression in a variety of
      host/vector systems.

PMID- 23973073
TI  - Heterotrimeric G proteins and microtubules.
AB  - Microtubules, major components of the cytoskeleton, play important roles in a
      variety of cellular functions including mitosis, intracellular transport, and the
      modulation of cell morphology. Several studies have demonstrated that specific G
      protein alpha subunits bind to tubulin with a high affinity (~130 nM) and elicit
      various functional effects on tubulin and microtubules. In this chapter, we
      present a description of the protocols for several methods that are used to
      determine the interaction between heterotrimeric G proteins and tubulin, as well
      as functional consequences of the interactions including protocols for protein
      purification, binding assays, tubulin GTPase assays, microtubule dynamics assays,
      and assays for cytoskeletal consequences of G-protein-coupled receptor signaling.

PMID- 23973074
TI  - Purification and biophysical analysis of microtubule-severing enzymes in vitro.
AB  - Microtubule-severing enzymes are a novel class of microtubule regulators. They
      are enzymes from the ATPases associated with various cellular activities family
      (AAA+) that utilize ATP to cut microtubules into smaller filaments. Discovered
      over 20 years ago, there are still many open questions about severing enzymes.
      Both cellular and biochemical studies need to be pursued to fully understand how
      these enzymes function mechanistically in the cell. Here, we present methods to
      express, purify, and test the biophysical nature of these proteins in vitro to
      begin to address the biochemical and biophysical mechanisms of this important and
      novel group of microtubule destabilizers.

PMID- 23973075
TI  - Measurement of in vitro microtubule polymerization by turbidity and fluorescence.
AB  - Tubulin polymerization may be conveniently monitored by the increase in turbidity
      (optical density, or OD) or by the increase in fluorescence intensity of
      diamidino-phenylindole. The resulting data can be a quantitative measure of
      microtubule (MT) assembly, but some care is needed in interpretation, especially
      of OD data. Buffer formulations used for the assembly reaction significantly
      influence the polymerization, both by altering the critical concentration for
      polymerization and by altering the exact polymer produced-for example, by
      increasing the production of sheet polymers in addition to MT. Both the turbidity
      and the fluorescence methods are useful for demonstrating the effect of MT
      stabilizing or -destabilizing additives. 

PMID- 23973076
TI  - Live-cell imaging of microtubules and microtubule-associated proteins in
      Arabidopsis thaliana.
AB  - Microtubules and microtubule-associated proteins (MAPs) play fundamental roles in
      plant growth and morphogenesis. The ability to observe microtubules and MAPs in
      living cells using fluorescent protein fusions has propelled plant scientists
      forward and given them the opportunity to answer longstanding biological
      questions. In combination with the genetic resources available in the model plant
      Arabidopsis thaliana, our mechanistic understanding of how the microtubule
      cytoskeleton affects plant life has dramatically increased. It is a simple
      process to construct transgenic A. thaliana plants that express fluorescent
      protein fusions by using the disarmed plant pathogen Agrobacterium tumefaciens.
      Several screening steps are necessary to ensure that the fusion protein
      accurately mimics the native protein because transgenes are inserted randomly
      into the A. thaliana genome. To image the fluorescent proteins in planta,
      confocal microscopy is used to alleviate issues caused by specimen thickness and
      autofluorescence.

PMID- 23973077
TI  - Investigating tubulin posttranslational modifications with specific antibodies.
AB  - Microtubules play highly diverse and essential roles in every eukaryotic cell.
      While built from conserved dimers of alpha- and beta-tubulin, microtubules can be
      diversified by posttranslational modifications in order to fulfill specific
      functions in cells. The tubulin posttranslational modifications: acetylation,
      detyrosination, polyglutamylation, and polyglycylation play important roles in
      microtubule functions; however, only little functional and mechanistic insight
      has been gained so far. The modification state of microtubules can be visualized
      with specific antibodies. A drawback is that detailed information about the
      specificities and limitations of these antibodies are not easily accessible in
      the literature. We provide here a comprehensive description of the currently
      available set of antibodies specific to tubulin modifications. Focusing on
      glutamylation antibodies, we discuss specific protocols that allow using these
      antibodies to gain semi-quantitative information on the levels and distribution
      of tubulin modifications in immunocytochemistry and immunoblot. 

PMID- 23973078
TI  - Purification and assembly of bacterial tubulin BtubA/B and constructs bearing
      eukaryotic tubulin sequences.
AB  - Bacterial tubulin BtubA/B is a close structural homolog of eukaryotic alphabeta
      tubulin, thought to have originated by transfer of ancestral tubulin genes from a
      primitive eukaryotic cell to a bacterium, followed by divergent evolution. BtubA
      and BtubB are easily expressed homogeneous polypeptides that fold spontaneously
      without eukaryotic chaperone requirements, associate into weak BtubA/B
      heterodimers and assemble forming tubulin-like protofilaments. These
      protofilaments coalesce into pairs and bundles, or form five-protofilament
      tubules proposed to share the architecture of microtubules. Bacterial tubulin is
      an attractive framework for tubulin engineering. Potential applications include
      humanizing different sections of bacterial tubulin with the aims of creating
      recombinant binding sites for antitumor drugs, obtaining well-defined substrates
      for the enzymes responsible for tubulin posttranslational modification, or
      bacterial microtubule-like polymeric trails for motor proteins. Several divergent
      sequences from the surface loops of bacterial tubulin have already been replaced
      by the corresponding eukaryotic sequences, yielding soluble folded chimeras. We
      describe the purification protocol of untagged bacterial tubulin BtubA/B by means
      of ion exchange, size exclusion chromatography, and an assembly-disassembly
      cycle. This is followed by methods and examples to characterize its assembly,
      employing light scattering, sedimentation, and electron microscopy. 

PMID- 23973079
TI  - Microtubule-associated proteins and tubulin interaction by isothermal titration
      calorimetry.
AB  - Microtubules play an important role in a number of vital cell processes such as
      cell division, intracellular transport, and cell architecture. The highly dynamic
      structure of microtubules is tightly regulated by a number of stabilizing and
      destabilizing microtubule-associated proteins (MAPs), such as tau and stathmin.
      Because of their importance, tubulin-MAPs interactions have been extensively
      studied using various methods that provide researchers with complementary but
      sometimes contradictory thermodynamic data. Isothermal titration calorimetry
      (ITC) is the only direct thermodynamic method that enables a full thermodynamic
      characterization (stoichiometry, enthalpy, entropy of binding, and association
      constant) of the interaction after a single titration experiment. This method has
      been recently applied to study tubulin-MAPs interactions in order to bring new
      insights into molecular mechanisms of tubulin regulation. In this chapter, we
      review the technical specificity of this method and then focus on the use of ITC
      in the investigation of tubulin-MAPs binding. We describe technical issues which
      could arise during planning and carrying out the ITC experiments, in particular
      with fragile proteins such as tubulin. Using examples of stathmin and tau, we
      demonstrate how ITC can be used to gain major insights into tubulin-MAP
      interaction.

PMID- 23973080
TI  - Methods for studying microtubule binding site interactions: zampanolide as a
      covalent binding agent.
AB  - In this chapter, we describe the methods used to determine the binding site and
      binding profile of zampanolide, a novel microtubule-stabilizing agent (MSA) that
      binds covalently to tubulin. These methods can be applied to other novel MSAs in
      which the binding site and mechanism of binding are unknown. Using the described
      methods, we have shown that zampanolide binds to the taxoid site on beta-tubulin,
      but unlike most other MSAs is able to covalently modify this site. The purpose of
      this chapter is to provide a step-by-step protocol for determining the binding
      site of a novel MSA.

PMID- 23973081
TI  - Studying kinetochore-fiber ultrastructure using correlative light-electron
      microscopy.
AB  - Electron microscopy (EM) has dominated high-resolution cellular imaging for over
      50 years, thanks to its ability to resolve on nanometer-scale intracellular
      structures such as the microtubules of the mitotic spindle. It is advantageous to
      view the cell of interest prior to processing the sample for EM. Correlative
      light-electron microscopy (CLEM) is a technique that allows one to visualize
      cells of interest by light microscopy (LM) before being transferred to EM for
      ultrastructural examination. Here, we describe how CLEM can be applied as an
      effective tool to study the spindle apparatus of mitotic cells. This approach
      allows transfected cells of interest, in desirable stages of mitosis, to be
      followed from LM to EM. CLEM has often been considered as a technically
      challenging and laborious technique. In this chapter, we provide step-by-step
      pictorial guides that allow successful CLEM to be achieved. In addition, we
      explain how it is possible to vary the sectioning plane, allowing spindles and
      microtubules to be analyzed from different angles, and the outputs that can be
      obtained from these methods when applied to the study of kinetochore fiber
      ultrastructure.

PMID- 23973082
TI  - Fluorescence-based assays for microtubule architecture.
AB  - In vitro fluorescence-based assays have enabled the direct observation of single
      microtubule-associated proteins (MAPs) alongside the measurement of microtubule
      growth and shrinkage. Fluorescence-based assays have not, however, been able to
      address questions of "microtubule architecture." Tubulin can form diverse polymer
      structures in vitro. Importantly, microtubules nucleated spontaneously have
      different numbers of protofilaments (pfs), ranging from 11-pf to 16-pf, as well
      as sheet-like structures, indicating flexibility in tubulin-tubulin bonds. This
      structural diversity influences microtubule dynamics and the binding of MAPs to
      microtubules. Observation of microtubule architecture has required the imaging of
      microtubules by electron microscopy (EM). Because EM requires chemical fixation
      or freezing, it has not been possible to observe, in real time, how microtubule
      dynamics might influence structure and vice versa; it also remains technically
      challenging to directly observe some MAPs, especially small ones, by EM. It is
      therefore imperative to develop fluorescence-based assays that enable the direct,
      real-time observation of microtubule architecture alongside growth, shrinkage,
      and MAP binding. In this chapter, we describe our efforts to control microtubule
      architecture for fluorescence-based assays. We also describe how microtubule
      structure can be probed with the help of GFP-tagged doublecortin, a MAP that
      binds preferentially to 13-pf microtubules.

PMID- 23973084
TI  - Using MTBindingSim as a tool for experimental planning and interpretation.
AB  - MTBindingSim is a program that enables users to simulate experiments in which
      proteins or other ligands (e.g., drugs) bind to microtubules or other polymers
      under various binding models. The purpose of MTBindingSim is to help researchers
      and students gain an intuitive understanding of binding behavior and design
      experiments to distinguish between different binding mechanisms. MTBindingSim is
      open-source, freely available software and can be found at
      bindingtutor.org/mtbindingsim. This chapter first describes the capabilities of
      MTBindingSim, including the experimental designs and protein-binding models that
      it simulates, and then discusses two examples in which MTBindingSim is utilized
      in an experimental context. In the first, MTBindingSim is used to investigate
      potential explanations for unusual behavior observed in the binding of the
      neuronal protein Tau to microtubules, demonstrating that some potential
      explanations are incompatible with the experimental data. In the second example,
      MTBindingSim is used to design experiments to examine the question of whether the
      plus-end tracking protein EB1 binds preferentially to the microtubule seam.

PMID- 23973083
TI  - Structure-function analysis of yeast tubulin.
AB  - Microtubules play essential roles in a wide variety of cellular processes
      including cell division, motility, and vesicular transport. Microtubule function
      depends on the polymerization dynamics of tubulin and specific interactions
      between tubulin and diverse microtubule-associated proteins. To date,
      investigation of the structural and functional properties of tubulin and tubulin
      mutants has been limited by the inability to obtain functional protein from
      overexpression systems, and by the heterogeneous mixture of tubulin isotypes
      typically isolated from higher eukaryotes. The budding yeast, Saccharomyces
      cerevisiae, has emerged as a leading system for tubulin structure-function
      analysis. Yeast cells encode a single beta-tubulin gene and can be engineered to
      express just one of two alpha isotypes. Moreover, yeast allows site-directed
      modification of tubulin genes at the endogenous loci expressed under the native
      promoter and regulatory elements. These advantageous features provide a
      homogeneous and controlled environment for analysis of the functional
      consequences of specific mutations. Here, we present the techniques to generate
      site-specific tubulin mutations in diploid and haploid cells, assess the ability
      of the mutated protein to support cell viability, measure overall microtubule
      stability, and define changes in the specific parameters of microtubule dynamic
      instability. We also outline strategies to determine whether mutations disrupt
      interactions with microtubule-associated proteins. Microtubule-based functions in
      yeast are well defined, which allows the observed changes in microtubule
      properties to be related to the role of microtubules in specific cellular
      processes. 

PMID- 23973085
TI  - Imaging individual spindle microtubule dynamics in fission yeast.
AB  - Microtubules exhibit dynamic instability, stochastically switching between
      infrequent phases of growth and shrinkage. In the cell, microtubule dynamic
      instability is further modulated by microtubule-associated proteins and motors,
      which are specifically tuned to cell cycle stages. For example, mitotic
      microtubules are more dynamic than interphase microtubules. The different
      parameters of microtubule dynamics can be measured from length versus time data,
      which are generally obtained from time-lapse acquisition using the optical
      microscope. The typical maximum resolution of the optical microscope is ~lambda/2
      or ~300 nm. This scale represents a challenge for imaging fission yeast
      microtubule dynamics specifically during early mitosis, where the bipolar mitotic
      spindle contains many short dynamic microtubules of ~1-MUm scale. Here, we
      present a novel method to image short fission yeast mitotic microtubules. The
      method uses the thermosensitive reversible kinesin-5 cut7.24(ts) to create
      monopolar spindles, where asters of individual mitotic microtubules are presented
      for imaging and subsequent analysis.

PMID- 23973086
TI  - Microtubules and microtubule-associated proteins. Preface.

PMID- 23973087
TI  - Influence of resin cement polymerization shrinkage on stresses in porcelain
      crowns.
AB  - OBJECTIVE: The aim of this study was to analyze the influence of polymerization
      shrinkage of the cement layer on stresses within feldspathic ceramic crowns,
      using experimentally validated FEA models for (1) increasing occlusal cement
      thickness; and, (2) bonded versus non-bonded ceramic-cement interfaces. METHODS:
      2-D axial symmetric models simulated stylized feldspathic crowns (1.5mm occlusal
      thickness) cemented with resin-cement layers of 50-500MUm on dentin preparations,
      being loaded (500N) or not. Ceramic-cement interface was either bonded or not.
      Cement was bonded to the dentin in all models. Maximum axial shrinkage of 0%, 1%,
      2%, 3%, 4% and 4.65% were simulated. The first principal stresses developing in
      the cementation surface at the center and at the occluso-axial line-angle of the
      crown were registered. RESULTS: Polymerization shrinkage of the cement increased
      tensile stresses in the ceramic, especially in loaded non-bonded crowns for
      thicker cement layers. Stresses in loaded non-bonded crowns increased as much as
      87% when cement shrinkage increased from 0% to 4.65% (100-187MPa), for a 500MUm
      thick cement. Increasing polymerization shrinkage strain raised the tensile
      stresses, especially at the internal occlusal-axial line-angle, for bonded
      crowns. SIGNIFICANCE: Changes in the polymerization shrinkage strain (from 0% to
      4.65%) have little effect on the tensile stresses generated at the cementation
      surface of the ceramic crowns, when the occlusal cement thickness is thin
      (approx. 50MUm for bonded crowns). However, as the cement becomes thicker
      stresses within the ceramic become significant.

PMID- 23973088
TI  - A kinematic comparison of successful and unsuccessful tennis serves across the
      elite development pathway.
AB  - While velocity generation is an obvious prerequisite to proficient tennis serve
      performance, it is also the only stroke where players are obliged to negotiate a
      unique target constraint. Therefore, the dearth of research attending to the
      accuracy component of the serve is surprising. This study compared the body,
      racquet and ball kinematics characterising successful serves and service faults,
      missed into the net, in two groups of elite junior female players and one
      professional female tennis player. Three-dimensional body, racquet and ball
      kinematics were recorded using a 22-camera VICON motion analysis system. There
      were no differences in body kinematics between successful serves and service
      faults, suggesting that service faults cannot be attributed to a single source of
      biomechanical error. However, service faults missing into the net are
      characterized by projection angles significantly further below the horizontal,
      implying that consistency in this end-point parameter is critical to successful
      performance. Regulation of this parameter appears dependent on compensatory
      adjustments in the distal elbow and wrist joints immediately prior to impact and
      also perceptual feedback. Accordingly, coordination of the distal degrees of
      freedom and a refined perception-action coupling appear more important to success
      than any isolated mechanical component of the service action. 

PMID- 23973089
TI  - Catastrophic neurologic syndrome with dramatic ECG changes.
AB  - Cerebrogenic ECG abnormalities, especially prominent T wave inversions and
      prolongation of the QT(U) interval, are well-described. Brady- and
      tachyarrhythmias, including polymorphic VT, have been also described in the
      setting of neurologic injury. We report an unusual case of a 22-year-old man who
      presented with idiopathic acute encephalopathy. His hospital course was
      complicated by persistent fevers, along with refractory seizures treated with
      propofol. Serial ECG findings included marked ventricular repolarization
      prolongation with bursts of torsade de pointes, diffuse ST elevations simulating
      extensive myocardial ischemia or infarction, as well as a Brugada-like pattern.
      To our knowledge, this case is the first reported with the combination of such
      findings in a patient with a catastrophic neurologic syndrome. 

PMID- 23973090
TI  - ECG Features that suggest a potentially life-threatening arrhythmia as the cause
      for syncope.
AB  - Syncope is a risk factor for sudden cardiac death (SCD) in many conditions
      associated with structural heart disease as well as inherited heart disease. The
      ECG in patients with syncope should be examined carefully for signs of structural
      heart disease, such as myocardial infarction or cardiomyopathy; signs of
      conduction system disease, such as bundle branch block or atrioventricular block;
      and signs of primary electrical disease. Important forms of cardiomyopathy
      accompanied by ECG changes include hypertrophic cardiomyopathy (HCM), and
      arrhythmogenic right ventricular dysplasia (ARVD/C). Common ECG findings in HCM
      include left ventricular hypertrophy by voltage, repolarization abnormalities,
      QRS widening, pseudoinfarction patterns, and slurred QRS upstroke mimicking delta
      waves. Classical ECG findings of ARVD/C include T-wave inversions and epsilon
      waves in the right precordial leads (V1-V3). Important forms of primary
      electrical disease which may result in syncope include Wolff-Parkinson-White
      syndrome, long QT syndrome, and Brugada syndrome, which is characterized by coved
      ST-segments in the right precordial leads, associated with a history of syncope,
      ventricular arrhythmia, or sudden cardiac death in probands or family member.
      There are three Brugada ECG patterns; however, only type I (spontaneous or
      induced) is considered diagnostic. Recently, studies have suggested that patients
      with J-point elevation or early repolarization pattern on ECG are at elevated
      risk of SCD. The clinical significance of finding early repolarization in a
      patient with syncope is unknown and should be a subject of future research.

PMID- 23973091
TI  - Repolarization features as detectable from electrograms and electrocardiograms.
AB  - This contribution discusses the feasibility of extracting the major features of
      repolarization: its spatio-temporal behaviour, and how much of its global or
      local behaviour might be deduced from signals that can be observed
      experimentally. The analysis presented is based on source-volume-conductor
      configurations ranging from the classic cable theory, with sources derived from
      reaction diffusion computations, to a realistic thorax model comprising a whole
      heart model with electric sources represented by the equivalent electric double
      layer. The analysis focuses on the fact that the local activation recovery
      interval (ARI) at regions activated by expanding wave fronts is significantly
      longer than those activated by contracting ones. The consequences of this effect
      on observed magnitude and wave form of recorded signals are illustrated. 

PMID- 23973092
TI  - Exercise-induced vasospastic angina after left atrial catheter ablation: a case
      report.
AB  - INTRODUCTION: Left atrial catheter ablation (LACA) is routinely used in the
      management of recurrent atrial fibrillation. CASE PRESENTATION: We report a
      patient suffering from vasospastic angina 2 months after a LACA procedure.
      Typical clinical symptoms, ST-segment changes during exercise test and successful
      treatment with nicorandil led to the diagnosis. According to our hypothesis,
      destruction of autonomic ganglia in the left atrium and resulting autonomic nerve
      tone imbalance might be the main determinants that have caused this phenomenon.
      CONCLUSION: Coronary spasms even weeks after LACA should draw attention to a
      possible association with the procedure.

PMID- 23973093
TI  - Recurrent life-threatening hyperkalemia without typical electrocardiographic
      changes.
AB  - Hyperkalemia is generally associated with electrocardiographic (ECG) changes and
      these changes have been used to follow the effects of high serum potassium (K+)
      levels on the heart. It is known that chronic renal impairment may diminish the
      toxic effects of hyperkalemia on ECG abnormality formation. (1-3) Here, we report
      a case of recurrent severe hyperkalemia without any significant ECG changes in a
      patient with normal baseline renal function. 

PMID- 23973094
TI  - Self-control and frequency of model presentation: effects on learning a ballet
      passe releve.
AB  - The purpose of this experiment was to examine the combined effects of self
      control and frequency of model presentation on learning a complex motor skill,
      i.e., ballet passe releve. Before practice started self-control participants were
      asked to choose two viewings or six viewings (before practice and then every five
      trials) and the externally controlled groups were yoked to their self-control
      counterparts. All participants completed 15 acquisition trials followed by 5
      trials for the immediate and 5 trials for the delayed retention tests 48 hours
      later. Dependent variables included cognitive representation scores, physical
      reproduction rankings, and balance time. Statistical analyses indicated that
      under limited physical practice conditions self-control and higher frequency of
      model presentation facilitated the development of cognitive representation and
      did not produce further benefits in movement reproductions and balance time. The
      results were discussed with respect to the social cognitive theory.

PMID- 23973095
TI  - Fenestrated endovascular repair for pararenal abdominal aortic aneurysms: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The development of endovascular technology has led to the
      introduction of fenestrated endovascular repair (f-EVAR) to treat pararenal
      abdominal aortic aneurysms (PRAAAs) that have been deemed unsuitable for standard
      endovascular repair. We performed a systematic review and meta-analysis of data
      from the literature to determine the outcomes of the fenestrated technology.
      METHODS: The MEDLINE, EMBASE, and Cochrane databases were searched to identify
      all studies published in English between January 1996 and May 2011 that reported
      on f-EVAR for PRAAAs. Separate meta-analyses were performed for primary outcomes
      (i.e., 30-day mortality, technical success rate, primary target vessel patency
      rate, and 12-month patency rate) and secondary outcomes (i.e., reintervention
      rate, target renal artery occlusion rate, and postoperative permanent dialysis
      rate). Subgroup analyses were performed to determine whether there were
      differences in outcomes between varying types of studies (prospective or
      retrospective). Regression analyses were performed to explore associations
      between outcomes and varying factors (i.e., mid-date of study, study size, and
      procedure time). RESULTS: Twelve studies conducted between 2006 and 2011 and
      consisting of a total of 776 cases of f-EVAR were enrolled. The pooled estimate
      for 30-day mortality was 2.52% (95% confidence interval [CI]: 1.55-4.08).
      Technical success was measured to be 92.8% (95% CI: 87.5-96.0). Primary target
      vessel patency was 98.3% (95% CI: 97.4-98.8). Twelve-month target vessel patency
      was 94.5% (95% CI: 92.1-96.2). The postoperative reintervention rate was 17.6%
      (95% CI: 12.0-25.1). The target renal artery occlusion rate was 6.1% (95% CI: 4.1
      8.8). The postoperative permanent dialysis rate was 2.6% (95% CI: 1.5-4.4).
      Subgroup analyses found no significant differences between the major outcomes of
      the retrospective studies and the prospective studies. Regression analyses
      suggested that large series had higher 12-month target vessel patency rates than
      small series. CONCLUSIONS: This study revealed that f-EVAR treatment for PRAAAs
      has acceptable early and mid-term outcomes.

PMID- 23973097
TI  - Comparison of dural repair techniques.
AB  - BACKGROUND CONTEXT: Incidental durotomy occurs in 1% to 17% of lumbar spine
      surgery. This is treated with watertight suture repair, often combined with a
      sealant. PURPOSE: To compare the hydrostatic strength of dural repair using
      various suture sizes, closure techniques, and adhesives. STUDY DESIGN: A novel in
      vitro hydrostatic calf spine model. OUTCOME MEASURES: Dural leakage as a function
      of hydrostatic pressure and leak area. METHODS: We compared surgical repair
      between 5-0 surgilon and 6-0 prolene suture, continuous locked versus interrupted
      suture, and the effectiveness of three adhesives hydrogel, cyanoacrylate, and
      fibrin glue. The leakage flow rate was compared among suture groups using
      analysis of variance (ANOVA). The percent reduction of leak area was determined
      for the sealants and compared using ANOVA. The study was funded from an
      intramural departmental grant. RESULTS: 6-0 Prolene was found to have
      significantly decreased leakage flow rate than 5-0 surgilon. We found no
      significant differences in the flow rate between the interrupted and continuous
      locked sutures. In most cases, leakage occurred from the needle holes around
      sutures. There was an 80% reduction in leak area with the hydrogel and
      cyanoacrylic sealants compared with only a 38% reduction with fibrin glue;
      however, there was no statistical difference between the leak rates using any of
      the sealants. CONCLUSION: 6-0 Prolene using either interrupted or locked
      techniques was the best at creating watertight closure of an incidental durotomy.
      If a watertight seal cannot be obtained, a hydrogel or a fibrin sealant will
      immediately improve the strength of repair. Newer sutures that have a larger
      diameter of suture relative to needle should be developed for use in dural
      repair.

PMID- 23973098
TI  - Surgeon-industry conflict of interest: survey of North Americans' opinions
      regarding surgeons consulting with industry.
AB  - BACKGROUND CONTEXT: Surgeon-industry conflict of interest (COI) has become a
      source of considerable interest. Professional medical societies, industry, and
      policy makers have attempted to regulate potential COI without consideration for
      public opinion. PURPOSE: The objective of this study was to report on the
      opinions of individuals representing the general public regarding surgeon
      industry consulting relationships. STUDY DESIGN/SETTING: Web-based survey.
      METHODS: Survey was administered using a "spine Web site," and opinions are
      collected on surgeon-industry consulting and regulation. Associations among
      responses to similar questions were assessed to ensure validity and subgroup
      analysis performed for respondent age, sex, education, insurance, employment, and
      patient status. RESULTS: Six hundred ten of 642 surveys had complete data. The
      sample population comprised more females and was older and more educated than the
      American population. About 80% of respondents felt it was ethical and either
      beneficial or of no influence to the quality of health care if surgeons were
      consultants for surgical device companies. Most felt disclosure of an industry
      relationship was important and paying surgeons royalties for devices, other than
      those they directly implant, would not affect quality of care. Respondents
      support multidisciplinary surgeon-industry COI regulation and trust doctors and
      their professional societies to head this effort. CONCLUSIONS: Despite the known
      potential negative impact of surgeon-industry COI on patient care, this study
      revealed that this does not seem to be reflected in the opinion of the general
      public. The respondents felt that disclosure is deemed one of the most important
      means of self-regulation and COI management, which is in agreement with current
      trends of most spine societies and journals that are increasing the stringency of
      disclosure policies.

PMID- 23973096
TI  - Gamma aminobutyric acidergic and neuronal structural markers in the nucleus
      accumbens core underlie trait-like impulsive behavior.
AB  - BACKGROUND: Pathological forms of impulsivity are manifest in a number of
      psychiatric disorders listed in DSM-5, including attention-deficit/hyperactivity
      disorder and substance use disorder. However, the molecular and cellular
      substrates of impulsivity are poorly understood. Here, we investigated a specific
      form of motor impulsivity in rats, namely premature responding, on a five-choice
      serial reaction time task. METHODS: We used in vivo voxel-based magnetic
      resonance imaging and ex vivo Western blot analyses to investigate putative
      structural, neuronal, and glial protein markers in low-impulsive (LI) and high
      impulsive rats. We also investigated whether messenger RNA interference targeting
      glutamate decarboxylase 65/67 (GAD65/67) gene expression in the nucleus accumbens
      core (NAcbC) is sufficient to increase impulsivity in LI rats. RESULTS: We
      identified structural and molecular abnormalities in the NAcbC associated with
      motor impulsivity in rats. We report a reduction in gray matter density in the
      left NAcbC of high-impulsive rats, with corresponding reductions in this region
      of glutamate decarboxylase (GAD65/67) and markers of dendritic spines and
      microtubules. We further demonstrate that the experimental reduction of de novo
      of GAD65/67 expression bilaterally in the NAcbC is sufficient to increase
      impulsivity in LI rats. CONCLUSIONS: These results reveal a novel mechanism of
      impulsivity in rats involving gamma aminobutyric acidergic and structural
      abnormalities in the NAcbC with potential relevance to the etiology and treatment
      of attention-deficit/hyperactivity disorder and related disorders.

PMID- 23973099
TI  - Complications of rhBMP-2 utilization for posterolateral lumbar fusions requiring
      reoperation: a single practice, retrospective case series report.
AB  - BACKGROUND CONTEXT: Recombinant human bone morphogenetic protein-2 (rhBMP-2)
      (INFUSE, Medtronic, Memphis, TN, USA) has been used off-label for posterolateral
      lumbar fusions for many years. PURPOSE: The goal of this study was to evaluate
      the complications requiring reoperation associated with rhBMP-2 application for
      posterolateral lumbar fusions. STUDY DESIGN/SETTING: During a 7-year period of
      time (2002-2009), all patients undergoing lumbar posterolateral fusion using
      rhBMP-2 (INFUSE) were retrospectively evaluated within a large orthopedic surgery
      private practice. PATIENT SAMPLE: A total of 1,158 consecutive patients were
      evaluated with 468 (40.4%) males and 690 (59.6%) females. OUTCOME MEASURES:
      Complications related to rhBMP were defined as reoperation secondary to
      symptomatic failed fusion (nonunion), symptomatic seroma formation, symptomatic
      reformation of foraminal bone, and infection. METHODS: Inclusion criteria were
      posterolateral fusion with rhBMP-2 implant and age equal to or older than 18
      years. Surgical indications and treatment were performed in accordance with the
      surgeon's best knowledge, discretion, and experience. Patients consented to
      lumbar decompression and arthrodesis using rhBMP-2. All patients were educated
      and informed of the off-label utilization of rhBMP-2. Patient follow-up was
      performed at regular intervals of 2 weeks, 6 weeks, 12 weeks, 6 months, 1 year,
      and later if required or indicated. RESULTS: Average age was 59.2 years, and body
      mass index was 30.7 kg/m2. Numbers of levels fused were 1 (414, 35.8%), 2 (469,
      40.5%), 3 (162, 14.0%), 4 (70, 6.0%), 5 (19, 1.6%), 6 (11, 0.9%), 7 (7, 0.6%), 8
      (4, 0.3%), and 9 (2, 0.2%). Patients having complications requiring reoperation
      were 117 of 1,158 (10.1%): symptomatic nonunion requiring redo fusion and
      instrumentation 41 (3.5%), seroma with acute neural compression 32 (2.8%), excess
      bone formation with delayed neural compression 4 (0.3%), and infection requiring
      debridement 26 (2.2%). Nonunion was related to male sex and previous BMP
      exposure. Seroma formation was significantly higher in patients with higher doses
      of rhBMP-2 (p=.050) and with more than 12 mg of rhBMP-2 (chi(2)=0.025). Bone
      reformation and neural compression at the laminectomy and foraminotomy sites
      occurred in a delayed fashion. Infection was associated with obesity and
      respiratory disease. Infections were noted with a greater BMP dose (p<.001), more
      than 12 mg (chi(2)<0.001), fusion more than three levels (chi(2)<0.001), and
      reexposed to BMP (chi(2)=0.023). CONCLUSIONS: rhBMP-2 utilization for
      posterolateral lumbar fusions has a low symptomatic nonunion rate. Prior rhBMP-2
      exposure and male sex were related to symptomatic nonunion formation. rhBMP-2
      associated neural compression acutely with seroma formation and delayed with
      foraminal bone formation is concerning and associated with higher rhBMP-2
      concentrations.

PMID- 23973100
TI  - Patient Education. Bone disease: preparing for your parathyroidectomy.

PMID- 23973101
TI  - Preoperative diagnostic workup before antireflux surgery: an evidence and
      experience-based consensus of the Esophageal Diagnostic Advisory Panel.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is a very prevalent disorder.
      Medical therapy improves symptoms in some but not all patients. Antireflux
      surgery is an excellent option for patients with persistent symptoms such as
      regurgitation, as well as for those with complete symptomatic resolution on acid
      suppressive therapy. However, proper patient selection is critical to achieve
      excellent outcomes. STUDY DESIGN: A panel of experts was assembled to review data
      and personal experience with regard to appropriate preoperative evaluation for
      antireflux surgery and to construct an evidence and experience-based consensus
      that has practical application. RESULTS: The presence of reflux symptoms alone is
      not sufficient to support a diagnosis of GERD before antireflux surgery.
      Esophageal objective testing is required to physiologically and anatomically
      evaluate the presence and severity of GERD in all patients being considered for
      surgical intervention. It is critical to document the presence of abnormal distal
      esophageal acid exposure, especially when antireflux surgery is considered, and
      reflux-related symptoms should be severe enough to outweigh the potential side
      effects of fundoplication. Each testing modality has a specific role in the
      diagnosis and workup of GERD, and no single test alone can provide the entire
      clinical picture. Results of testing are combined to document the presence and
      extent of the disease and assist in planning the operative approach. CONCLUSIONS:
      Currently, upper endoscopy, barium esophagram, pH testing, and manometry are
      required for preoperative workup for antireflux surgery. Additional studies with
      long-term follow-up are required to evaluate the diagnostic and therapeutic
      benefit of new technologies, such as oropharyngeal pH testing, multichannel
      intraluminal impedance, and hypopharyngeal multichannel intraluminal impedance,
      in the context of patient selection for antireflux surgery.

PMID- 23973102
TI  - Comparison study of acellular dermal matrices in complicated hernia surgery.
AB  - BACKGROUND: Damage control surgery and management of the open abdomen has led to
      a significant improvement in survival in trauma and emergency surgical patients.
      However, subsequent abdominal reconstruction has become a significant challenge.
      The objective of this study was to compare 2 different acellular dermal matrices
      in regard to hernia recurrence and complications in patients who present with a
      large complicated ventral hernia as a result of trauma or emergency surgery.
      STUDY DESIGN: A prospective quasi-experimental time-interrupted series design was
      used to evaluate the incidence of hernia recurrence in trauma/emergency surgery
      patients who had a ventral hernia repair with a biologic matrix. From January
      2005 to December 2007, 55 patients with a complicated ventral hernia were
      repaired with AlloDerm (Life Cell Corporation). Beginning in February 2008 to
      January 2010, 40 patients with the same criteria were repaired with FlexHD
      (Musculoskeletal Transplant Foundation) and followed prospectively over the
      following year. The primary outcome for this study was hernia recurrence
      (functional or real) at 1 year. Other outcomes variables included abdominal
      laxity, seroma formation, and wound or intra-abdominal infection. RESULTS: There
      was no significant difference in age, sex, and body mass index between the
      groups. In addition, there was no significant difference in the mean hernia size
      and size of the acellular dermis that was inserted. At 1 year postsurgery, all of
      the AlloDerm patients were diagnosed with recurrence requiring a second formal
      repair. Eleven patients (31%) whose hernias were repaired with FlexHD were
      diagnosed with a recurrence requiring a second formal repair. CONCLUSIONS: FlexHD
      appears to have reduced the recurrence and laxity rates while maintaining a
      similar complication profile compared with AlloDerm in trauma/emergency surgery
      patients with large complicated ventral hernias.

PMID- 23973103
TI  - Risk analysis of early implant loss after immediate breast reconstruction: a
      review of 14,585 patients.
AB  - BACKGROUND: Early prosthesis loss is an infrequent but serious complication after
      breast reconstruction. We assessed perioperative risk factors associated with
      early device loss after immediate breast reconstruction (IBR) using the ACS-NSQIP
      datasets. STUDY DESIGN: We reviewed the 2005 to 2011 ACS-NSQIP databases
      identifying encounters for CPT codes 19357 and 19340. Patients were identified as
      experiencing a "loss of graft/prosthetic" based on a standard dataset variable.
      Patients who experienced a device loss were compared with those who did not with
      respect to perioperative characteristics. RESULTS: We identified 14,585 patients
      with an average age of 50.9 +/- 10.6 years. A multivariate regression analysis
      determined that age (>55 years) (odds ratio [OR] 1.66, p = 0.013) (risk score =
      1), class II obesity (OR 3.17, p < 0.001) (risk score = 3), class III obesity (OR
      2.41, p = 0.014) (risk score = 3), active smoking (OR 2.95, p < 0.001) (risk
      score = 3), bilateral reconstruction (OR 1.67, p = 0.007) (risk score = 1), and
      direct-to-implant (DTI) reconstruction (OR 1.69, p = 0.024) (risk score = 1) were
      associated with early device loss. Odds ratios were used to assign weighted risk
      scores to each patient, and risk categories were broken into low risk (0 to 1, n
      = 9,349), intermediate risk (2 to 5, n = 5,001), and high risk (>= 6, n = 233)
      groups. The risk of device loss was significantly higher with increased risk
      score (0.39% vs 1.48% vs 3.86%, p < 0.001). CONCLUSIONS: Early device loss
      following IBR is a complex multifactorial process related to identifiable
      preoperative risk factors. This study demonstrated that age, obesity, smoking,
      bilateral procedures, and DTI reconstructions are associated with increased risk
      of implant loss.

PMID- 23973104
TI  - Surgical Safety Checklist compliance: a job done poorly!
AB  - BACKGROUND: The Surgical Safety Checklist (SSC) has been introduced as an
      effective tool for reducing perioperative mortality and complications. Although
      reported completion rates are high, objective compliance is not well defined. The
      purpose of this retrospective analysis is to determine SSC compliance as measured
      by accuracy and completion, and factors that can affect compliance. STUDY DESIGN:
      In September 2010, our institution implemented an adaptation of the World Health
      Organization's SSC in an effort to improve patient safety and outcomes. A tool
      was developed for objective evaluation of overall compliance (maximum score 40)
      that was an aggregate score of completion and accuracy (20 each). Random samples
      of SSCs were analyzed at specific, predefined, time points throughout the first
      year after implementation. Procedure start time, operative time, and case
      complexity were assessed to determine association with compliance. RESULTS: A
      total of 671 SSCs were analyzed. The participation rate improved from 33% (95 of
      285) at week 1 to 94% (249 of 265) at 1 year (p < 0.0001, chi-square test). Mean
      overall compliance score was 27.7 (+/- 5.4 SD) of 40 possible points (69.3% +/-
      13.5% of total possible score; n = 671) and did not change over time. Although
      completion scores were high (16.9 +/- 2.7 out of 20 [84.5% +/- 13.6%]), accuracy
      was poor (10.8 +/- 3.4 out of 20 [54.1% +/- 16.9%]). Overall compliance score was
      significantly associated with case start-time (p < 0.05), and operative time and
      case complexity showed no association. CONCLUSIONS: Our data indicate that
      although implementation of an SSC results in a high level of overall
      participation and completion, accuracy remained poor. Identification of barriers
      to effective use is needed, as improper checklist use can adversely affect
      patient safety.

PMID- 23973105
TI  - [Primary intraosseous mucoepidermoid carcinoma of the jaws].
AB  - INTRODUCTION: A mucoepidermoid carcinoma (MEC) is a malignant salivary gland
      tumor. Its primitive intraosseous maxillary localization is rare. We report a
      case with a difficult diagnosis. CASE REPORT: A 42-year-old female patient
      consulted atypical right sinus area pain. The CT scan revealed a heterogeneous
      tumor lyzing the right maxillary. The surgical treatment was broad resection. The
      pathological examination indicated an intramaxillary MEC. The surgical treatment
      was completed by postoperative radiotherapy. DISCUSSION: Primary intraosseous MEC
      of the jaws is rare and often affects the mandible. Its intraosseous maxillary
      localization is even rarer. Its etiopathogenesis is still unknown. The treatment
      is usually surgical, and the prognosis is based on histological criteria.

PMID- 23973106
TI  - [Extended resection and radiotherapy for primary intraosseous maxillary
      carcinoma].
AB  - INTRODUCTION: Primary intraosseous maxillary carcinoma is a rare squamous cell
      carcinoma developing from remnants of the odontogenic epithelium. Risk factors
      are unknown and it may occur at any age. Little epidemiological data is available
      and few series include a sufficient number of patients. We assessed the prognosis
      of these tumors after wide exeresis (margin of 2 cm) followed by adjuvant
      radiotherapy. METHODS: We reviewed the treatment and outcome data in nine cases
      of primary intraosseous maxillary carcinoma from 1995 to 2010. The WHO diagnostic
      criteria were used. We analyzed the demographic, clinical, and radiological data,
      as well as the type of treatment and the outcome of patients. RESULTS: The gender
      ratio was 3.5/1, and the mean age 40.2 years. The most frequent presentation was
      a unilocular osteolytic lesion with an irregular contour, between 24 and 60 mm,
      in the mandibular angle. Extended tumor resection was performed in all patients.
      Reconstruction was performed with a fibula flap in seven patients. Five patients
      underwent adjuvant radiotherapy. The survival rate at 2 years was 100%. The mean
      follow-up was 6.9 years (2-14 years) at the end of the study. Two patients were
      treated for a relapse and one died after 3 years of follow-up. DISCUSSION: The
      combined treatment was efficient on primary intraosseous maxillary carcinoma. The
      diagnosis is made with strict clinical, radiological, and histological criteria.
      The intraosseous location of these tumors requires an early diagnosis and
      aggressive treatment combining broad exeresis followed by adjuvant radiotherapy
      to avoid recurrence and have an optimal survival rate.

PMID- 23973107
TI  - [Extremely rapid progression of oral cavity carcinosarcoma].
AB  - INTRODUCTION: Carcinosarcoma is a very rare malignant tumor of the salivary
      glands including accessory salivary gland, associating malignant mesenchymal and
      epithelial tissue. It usually occurs after 50 years of age. Its prognosis is very
      poor. We present a case of carcinosarcoma having evolved extremely rapidly. CASE
      REPORT: A 38-year-old female patient presented with an inflammatory budding
      lesion of the mandibular gingival mucosa. The diagnosis of carcinosarcoma having
      developed from an accessory salivary gland was made after testing biopsies. The
      carcinosarcoma could not be removed because of an extremely rapid tumor growth,
      its volume having increased three fold in 2 weeks. The patient died in a few
      weeks. DISCUSSION: The occurrence of carcinosarcoma at 38 years of age is
      exceptionally rare. The rapidly evolution of carcinosarcoma is well documented.
      It may prevent complete excision. This case led us to suggest an emergency
      management for carcinosarcomas.

PMID- 23973108
TI  - CALIPER: Supporting the steps forward in paediatric laboratory measurement.

PMID- 23973109
TI  - Third or more repeat hepatectomy for recurrent hepatocellular carcinoma.
AB  - BACKGROUND: We sought to evaluate the surgical results of third or more repeat
      hepatectomy for recurrent hepatocellular carcinoma (HCC). The role of repeat
      hepatectomy for recurrent HCC, especially in cases with third or more repeat
      hepatectomy, is controversial. METHODS: We performed A retrospective, cohort
      study to analyze the surgical results of repeat hepatectomy performed at a single
      medical center from 1989 to 2011. A total of 1,000 hepatectomies for HCC were
      divided into 3 groups: A first hepatectomy group (n = 791), second hepatectomy
      group (n = 163), and third or more hepatectomy group (n = 46). Operative results
      and patient prognoses were compared among the 3 groups. RESULTS: There were no
      differences in early surgical results such as mortality and morbidity among the 3
      groups. The 5-year survival rates after the first, second, and third or more
      hepatectomy were 67%, 60%, and 43%, respectively (P = .1913). There was a
      significant difference in disease-free survival among the 3 groups, and the 5
      year disease-free survival rates after first, second, and third or more
      hepatectomy were 37%, 29%, and 18%, respectively (P = .0169). CONCLUSION: Third
      or more repeat hepatectomy for recurrent HCC was performed safely and associated
      with relatively long-term survival. Third or more repeat hepatectomy for
      recurrent HCC seems justified, but high rate of HCC recurrence remains a problem.

PMID- 23973110
TI  - The role of the dual console in robotic surgical training.

PMID- 23973111
TI  - Relationship between preoperative symptoms and improvement of quality of life in
      patients undergoing elective inguinal herniorrhaphy.
AB  - BACKGROUND: Improvement of quality of life (QoL) is the ultimate goal for
      inguinal hernia repair. Data on QoL before surgery are scarce, and it is not
      known whether postoperative improvement of QoL relates to preoperative symptoms.
      METHODS: Symptoms and self-reported QoL were evaluated and compared with matched
      control patients from a normal population in 309 male subjects before and 1 year
      after unilateral open inguinal hernia repair. RESULTS: Before operation, 91 % of
      patients noted a bulge, whereas 75% had symptoms, most commonly pain (64%); the
      other 25% were asymptomatic. Physical QoL scores (physical component score) were
      decreased in patients compared with matched controls (median [interquartile
      range] PCS 47 [38-53] vs 54 [48-57] P < .05), whereas mental scores (mental
      component score) were not affected (P = .401). PCS was less in patients with pain
      compared with those without pain (44 [35-50] vs 53 [48-56] P = .001). In patients
      without pain, no difference was found compared with control patients (P = .57).
      At 1 year after surgery, PCS was increased to 55 (53-57) in patients and was
      slightly greater than control patients (P < .05). The increase was greater in
      patients who reported preoperative pain (from 44 [35-50] to 55 [52-57] vs from 53
      [48-56] to 56 [54-57], P < .00001). MCS did not change after inguinal
      herniorrhaphy. CONCLUSION: Preoperative affection as well as postoperative
      improvement in self-reported physical QoL seems to be strongly associated with
      preoperative inguinal pain. This finding underscores that occurrence of
      preoperative pain is an important symptom to evaluate before taking the decision
      to operate for inguinal hernia.

PMID- 23973112
TI  - Margin status, recurrence pattern, and prognosis after resection of pancreatic
      cancer.
AB  - BACKGROUND: Controversy persists as to whether positive operative margins are an
      independent prognostic factor for resected pancreatic cancer. This study
      evaluated the impact of the resection margin status on the patterns of recurrence
      and prognosis after resection for pancreatic cancer. METHODS: A total of 208
      patients with pancreatic cancer who underwent resection with curative intent were
      studied retrospectively. All patients underwent pancreatectomy (164
      pancreatoduodenectomies, 42 distal pancreatectomies, and 2 total
      pancreatectomies) intended to achieve R0 resection. They were divided into three
      groups on the basis of the following margin status: R(>1 mm), R(0-1 mm), and R(0
      mm). The postoperative survival and recurrence patterns were evaluated in
      relation to the margin status. Multivariate analyses were performed to evaluate
      the factors influencing the overall survival. RESULTS: The resection margin was
      R(>1 mm) in 134 patients (65%), R(0-1 mm) in 40 (19%), and R(0 mm) in 34 patients
      (16%). The margin status correlated with the rate of local recurrence; 8% in R(>1
      mm), 20% in R(0-1 mm), and 50% in R(0 mm) patients. In contrast, the incidence of
      recurrence at other sites, such as the lymph nodes, peritoneum, liver and other
      distant organs, were almost identical among the three groups. The median survival
      time was 26 months in R(>1 mm), 30 months in R(0-1 mm), and 23 months in R(0 mm)
      patients (P = not significant). The multivariate analyses revealed that lymph
      node metastases and poor differentiation were correlated with poor survival.
      CONCLUSION: In the setting of pancreatectomy, when we evaluated the definitions
      of R0 resection, the margin status influenced the local recurrence rate but had
      no impact on the patients' survival.

PMID- 23973113
TI  - Oncolytic vesicular stomatitis virus as a treatment for neuroendocrine tumors.
AB  - BACKGROUND: Therapeutic goals for neuroendocrine tumors (NETs) not amenable to
      operative cure are limited to relieving symptoms and slowing progression. Many
      malignancies acquire defective antiviral responses as they undergo unregulated
      proliferation. Therefore, we explored the abilities of recombinant wild-type
      vesicular stomatitis virus and an attenuated matrix protein mutant (M51R-VSV) to
      exploit defective antiviral pathways in NETs. METHODS: Viral infectivity and
      lethality were evaluated in a panel of human NET cell lines H727, UMC-11, and
      CNDT2.5. We evaluated beta-interferon pathways in these cells to define the
      acquired defect. Murine xenografts were treated with a single intratumoral
      injection of M51R-VSV to study viral efficacy in vivo. RESULTS: VSV infected >99%
      of cells within 24 hours and killed >95% within 72 hours. NET cells did not
      produce relevant amounts of beta-interferon after infection, but exogenous beta
      interferon protected cells from oncolysis. Treatment with M51R-VSV resulted in
      suppressed tumor growth (mean value +/- standard error of the mean) compared with
      mock-infected xenografts for H727 (87 +/- 72% vs. 2,197 +/- 335%; P < .001), UMC
      11 (13 +/- 59% vs. 1,471 +/- 324%; P < .001), and CNDT2.5 (81 +/- 121% vs. 1,576
      +/- 349%; P = .001). CONCLUSION: VSV infects and kills human NETs by exploiting
      their inability to produce a type I antiviral response. Therefore, M51R-VSV is an
      excellent candidate for the treatment of advanced NETs.

PMID- 23973114
TI  - Hurthle cell carcinoma: an update on survival over the last 35 years.
AB  - BACKGROUND: Hurthle cell carcinoma (HCC) of the thyroid is a variant of
      follicular cell carcinoma (FCC). A low incidence and lack of long-term follow-up
      data have caused controversy regarding the survival characteristics of HCC. We
      aimed to clarify this controversy by analyzing HCC survival over a 35-year period
      using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS:
      Cases of HCC and FCC were extracted from the SEER-9 database (1975-2009). Five-
      and 10-year survival rates were calculated. We compared changes in survival over
      time by grouping cases into 5-year intervals. RESULTS: We identified 1,416 cases
      of HCC and 4,973 cases of FCC. For cases diagnosed from 1975 to 1979, HCC showed
      a worse survival compared with FCC (5 years, 75%; 95% confidence interval [CI],
      60.2-85) versus 88.7% (95% CI, 86-90.8; 10 years, 66.7% [95% CI, 51.5-78.1] vs.
      79.7% [95% CI, 76.5-82.6]). For cases diagnosed from 2000 to 2004 we found no
      difference in 5-year survival between HCC and FCC (91.1% [95% CI, 87.6-93.7] vs.
      89.1% [95% CI, 86.5-91.2]). For cases diagnosed from 1995 to 1999, there was no
      difference in 10-year survival between HCC and FCC (80.9% [95% CI, 75.6-85.2] vs.
      83.9% [95% CI, 80.8-86.6]). HCC survival improved over the study period while FCC
      survival rates remained stable (increase in survival at 5 years, 21.7% vs. 0.4%;
      at 10 years, 21.3% vs. 5.2%). Improvement in HCC survival was observed for both
      genders, in age >=45 years, in local and regional disease, for tumors >4 cm, and
      with white race. CONCLUSION: HCC survival has improved dramatically over time
      such that HCC and FCC survival rates are now the same. These findings explain how
      studies over the last 4 decades have shown conflicting results regarding HCC
      survival; however, our data do not explain why HCC survival has improved.

PMID- 23973115
TI  - Attributable costs of differentiated thyroid cancer in the elderly Medicare
      population.
AB  - BACKGROUND: Little is known about costs associated with differentiated thyroid
      cancer (DTC) and follow-up care. This study used data from the Surveillance
      Epidemiology and End Results (SEER) database to examine cumulative costs
      attributable to disease stage and treatment options of DTC in elderly patients
      over 5 years. METHODS: We identified 2,823 patients aged >65 years with DTC and
      5,646 noncancer comparison cases from SEER Medicare data between 1995 and 2005.
      Cumulative costs were obtained by estimating average costs/patient in each month
      up to 60 months after diagnosis. We performed multivariate analyses of costs by
      fitting each monthly cost to linear models, controlling for demographics and
      comorbidities. Marginal effects of covariates were obtained by summing
      coefficients over 60 months. RESULTS: Cumulative costs were $17,669/patient the
      first year and $48,989/patient 5 years after diagnosis. Regional disease was
      associated with higher costs at 1 year ($9,578) and 5 years ($8,902). Distant
      disease was associated with 1-year costs of $28,447 and 5-year costs of $20,103.
      Patients undergoing surgery and radiation had a decrease in cost of $722 at 5
      years. CONCLUSION: DTC in the elderly is associated with significant economic
      burden largely attributable to patient demographics, stage of disease, and
      treatment modalities.

PMID- 23973116
TI  - [Conservative surgical treatment for diabetic foot ulcers under the metatarsal
      heads. A retrospective case-control study].
AB  - AIM OF THE STUDY: The plantar neuropathic ulcer is a classical and frequent
      complication of a pathology recognized as pandemic by the WHO: diabetes. Even if
      frequently encountered during medical practice, the neuropathic ulcer remains
      poorly understood in its pathophysiology. Its treatment is usually long and
      disappointing, resulting too often in an amputation. Paradoxically, medical
      literature is particularly scarce on the subject of surgical approaches to the
      plantar neuropathic ulcer. Beyond the cases of vascular lesions requiring above
      all a technique of revascularization, we have tested out an original approach
      enabling the surgical treatment of an overt neuropathic ulcer. Our purpose was to
      correct the architecture of the foot for a superior distribution of foot support
      points. We performed subtraction osteotomies ahead of the neuropathic ulcer in
      order to redress the deformed bone axis. Standing with full weight on the foot is
      prescribed from the following day of the intervention in almost all cases.
      PATIENTS AND METHODS: We have evaluated the effectiveness of this innovative
      conservative surgical treatment on neuropathic ulcers of metatarsal heads by
      comparing it with the usual medical treatment. Two groups of patients have thus
      been analysed for this retrospective comparative study in order to determinate
      whether the use of this surgical technique benefits the patient. The studied
      criteria were healing time, recurrence rate, amputation rate and overall failure
      rate of the treatment, represented by the occurrence of the event "recurrence or
      amputation". RESULTS: All the differences found were in favour of the surgical
      technique with, in particular, significant differences in healing time,
      amputation rate and occurrence rate of the event "recurrence or amputation". The
      difference in recurrence rate was also clearly in favour of the surgery group,
      but it was not significant. CONCLUSION: The conservative surgical treatment by
      proximal osteotomy is therefore an innovative technique enabling a significant
      improvement in healing time and treatment after-effects of neuropathic ulcers in
      non-arteritis diabetic patients.

PMID- 23973117
TI  - Molecular diagnostic profiling of lung cancer specimens with a semiconductor
      based massive parallel sequencing approach: feasibility, costs, and performance
      compared with conventional sequencing.
AB  - In the context of personalized oncology, screening for somatic tumor mutations is
      crucial for prediction of an individual patient's response to therapy. Massive
      parallel sequencing (MPS) has been suggested for routine diagnostics, but this
      technology has not been sufficiently evaluated with respect to feasibility,
      reliability, and cost effectiveness with routine diagnostic formalin-fixed,
      paraffin-embedded material. We performed ultradeep targeted semiconductor-based
      MPS (190 amplicons covering hotspot mutations in 46 genes) in a variety of
      formalin-fixed, paraffin-embedded diagnostic samples of lung adenocarcinoma
      tissue with known EGFR mutations (n = 28). The samples reflected the typical
      spectrum of tissue material for diagnostics, including small biopsies and samples
      with low tumor-cell content. Using MPS, we successfully sequenced all samples,
      with a mean read depth of 2947 reads per amplicon. High-quality sequence reads
      were obtained from samples containing >=10% tumor material. In all but one
      sample, variant calling identified the same EGFR mutations as were detected by
      conventional Sanger sequencing. Moreover, we identified 43 additional mutations
      in 17 genes and detected amplifications in the EGFR and ERBB2 genes. MPS
      performance was reliable and independent of the type of material, as well as of
      the fixation and extraction methods, but was influenced by tumor-cell content and
      the degree of DNA degradation. Using sample multiplexing, focused MPS approached
      diagnostically acceptable cost rates. 

PMID- 23973118
TI  - [Place of the mini-sling in the treatment of female stress urinary incontinence].
AB  - OBJECTIVE: Evaluate the place of sub-urethral mini-slings in the treatment of
      female stress urinary incontinence. MATERIAL AND METHODS: Review of the
      literature on 43 publications (comparative and prospective studies) more than
      6443 patients who underwent for the treatment of urinary incontinence, a mini
      strip type TVT(r), TVT-S(r), MiniArc(r), Ajust(r), Needleless(r), Solyx(r), or
      Ophira(r) in comparison to the conventional urethral sling. The comparison used
      objective (cough stress test and pad weight test) and subjective criteria
      (quality of life questionnaire). The papers have also studied the complication
      associated with these new techniques. RESULTS: The overall effectiveness of this
      surgery varied between 40 to 84% for TVT-S(r), 69 to 92% for MiniArc(r), 80 to
      91% for Ajust(r), 87% for Needleless(r), 95% for Solyx(r) and 85% for Ophira(r).
      The efficacy on incontinence was higher with the TVT(r) TVT-S(r) and the
      MiniArc(r) (P=0.01 to 0.05). TVT-O(r) efficacy was higher than TVT-S(r) (P<0.01
      and P=0.02). Conventional slings seems to be more efficient than TVT-S(r) and
      MiniArc(r) mini-slings. Ajust(r) mini-sling seems to be as efficient as
      MiniArc(r) and TVT-S(r) mini-sling and TVT-O(r). It showed a decrease in the
      intensity of postoperative pain (P<0.001), faster return to normal activities
      (P=0.025) and use of a common local anesthetic to the adjustable mini-sling.
      CONCLUSION: It seems that the adjustable mini-sling is currently the best
      compromise in terms of effectiveness and complications if the choice had to be
      among the mini-sling in the treatment of stress urinary incontinence.

PMID- 23973119
TI  - [Long-term complication of laparoscopic uterine morcellation: iatrogenic
      parasitic myomas].
AB  - OBJECTIVES: Identify parasitic myomas following uterine laparoscopic morcellation
      and describe the circumstances of diagnosis, management, potential consequences
      and possible preventive measures. METHODS: Retrospective study of observed cases
      in a university hospital between 2000 and 2012 and review of the literature.
      RESULTS: Five cases were identified in our department. Pelvic pain was the main
      symptom in three patients while one was asymptomatic and one consulted for a
      cystocele. The average time to diagnosis was 88 months (3-192). Surgical removal
      was performed in four cases by laparoscopy and vaginally for one case.
      Histological examination showed typical leiomyomas, but in one case, an atypical
      leiomyoma with limited experience for a typical primary lesion. In the
      literature, there are about 50 cases. One required a bowel resection and for
      another one, after subtotal hysterectomy, histological examination showed complex
      atypical endometrial hyperplasia for normal endometrium initially. CONCLUSIONS:
      This study should draw the attention of laparoscopic surgeon. It emphasizes,
      beyond a potential reoperation, a risk of atypical histological secondary
      processing. Surgical resection should be discussed even in case of asymptomatic
      lesions.

PMID- 23973120
TI  - Foraging to settled life: a comparative study of anthropometry and nutrition of
      Onges of Little Andaman Island.
AB  - The aim of this study is to examine the impact of forced settlement among the
      foraging Onges, which induced them to change their subsistence from full time
      foragers to settled consumer. Anthropometric study along with dietary
      investigation was considered before and afterwards they were forcibly settled.
      The anthropometric variables and indices show gradual increase among the Onges
      males but not so much in females. High prevalence of overweight and obesity is
      also reported. Comparison with other Andaman Islanders indicates that the group
      which was under the developmental schemes (forced to settle), is showing more
      mean values of anthropometric variables with prevalence of overweight and obesity
      than the group, which was not under the influence of developmental programme.
      Their dietary pattern and physical activity changed to a great extent. The
      protein content of the diets reduced significantly and the fat along with
      carbohydrates increased to a substantial amount. The contribution of protein to
      calories has been reduced substantially and now it is only around 10%, whereas in
      the past it was above 30%. Caloric intakes increased more than two times, while
      the physical activity level reduced to about half time. Decreased mobility and
      altered food habits are the probable reason for the gradual increase of body
      dimensions and prevalent overweight and obesity, which are the outcomes of forced
      settlement. 

PMID- 23973121
TI  - Intertidal macrofauna and environmental stress at a riverine-marine boundary.
AB  - A field experiment was carried out to test the effect of pore water salinity on
      the macrobenthic assemblages in an estuarine region of the Tagus estuary
      (Portugal) subjected to wide fluctuations in salinity. The conditions at the
      experimental site ranged from freshwater (minimum salinity 0.2) to mesohaline
      (maximum salinity 15.3). The experimental site was affected by an unexpected
      deposition of fluid mud during summer. Redundancy Analysis discriminated the
      experimental treatments along the first canonical ordination axis. The analysis
      also revealed an experimental gradient of increasing environmental stress, in
      which the minimal presence of organisms corresponded to treatments representing a
      high level of environmental stress. Sediment dynamics and saline fluctuations
      were the major factors that, together, determined the low macrofaunal abundance
      and species diversity at the experimental site. The most abundant macrofaunal
      species in this harsh environment were the polychaetes Hediste diversicolor and
      Streblospio shrubsolii. 

PMID- 23973122
TI  - Robotic tissue tracking for beating heart mitral valve surgery.
AB  - The rapid motion of the heart presents a significant challenge to the surgeon
      during intracardiac beating heart procedures. We present a 3D ultrasound-guided
      motion compensation system that assists the surgeon by synchronizing instrument
      motion with the heart. The system utilizes the fact that certain intracardiac
      structures, like the mitral valve annulus, have trajectories that are largely
      constrained to translation along one axis. This allows the development of a real
      time 3D ultrasound tissue tracker that we integrate with a 1 degree-of-freedom
      (DOF) actuated surgical instrument and predictive filter to devise a motion
      tracking system adapted to mitral valve annuloplasty. In vivo experiments
      demonstrate that the system provides highly accurate tracking (1.0 mm error) with
      70% less error than manual tracking attempts.

PMID- 23973123
TI  - A special Osteoarthritis and Cartilage issue on pain in osteoarthritis.

PMID- 23973125
TI  - The relationship between quadriceps muscle weakness and worsening of knee pain in
      the MOST cohort: a 5-year longitudinal study.
AB  - OBJECTIVE: To determine whether quadriceps weakness is associated with elevated
      risk of worsening knee pain over 5 years. METHODS: The Multicenter Osteoarthritis
      Study (MOST) is a longitudinal study of 50-79-year-old adults with knee
      osteoarthritis (OA) or known risk factors for knee OA. The predictor variable was
      baseline isokinetic quadriceps strength. Covariates included baseline body mass
      index (BMI), physical activity level, and history of knee surgery. The outcome
      was worsening pain reported on the Western Ontario and McMaster Universities
      (WOMAC) Osteoarthritis Index pain subscale or knee replacement surgery between
      baseline and 5-year follow-up. Analyses were knee-based and used generalized
      estimating equations, stratified by sex to assess whether the lowest compared
      with the highest tertile of baseline quadriceps strength was associated with an
      increased risk of worsening knee pain at 5-year follow-up, controlling for age,
      BMI, history of knee surgery, and physical activity level as well as correlation
      between knees within participants. RESULTS: Analyses of worsening knee pain
      included 4,648 knees from 2,404 participants (61% female). Men with lower
      quadriceps strength did not have a higher risk of worsening knee pain (RR {95%
      CI} = 1.01 {0.78-1.32}, P = 0.9183). However, women in the lowest compared with
      the highest strength tertile had a 28% increased risk of worsening knee pain (RR
      {95% CI} = 1.28 {1.08-1.52}, P = 0.0052). CONCLUSION: Quadriceps weakness was
      associated with an increased risk of worsening of knee pain over 5 years in
      women, but not in men.

PMID- 23973124
TI  - The epidemiology and impact of pain in osteoarthritis.
AB  - Osteoarthritis (OA) is the most common form of arthritis and a leading cause of
      disability worldwide, largely due to pain, the primary symptom of the disease.
      The pain experience in knee OA in particular is well-recognized as typically
      transitioning from intermittent weight-bearing pain to a more persistent, chronic
      pain. Methods to validly assess pain in OA studies have been developed to address
      the complex nature of the pain experience. The etiology of pain in OA is
      recognized to be multifactorial, with both intra-articular and extra-articular
      risk factors. Nonetheless, greater insights are needed into pain mechanisms in OA
      to enable rational mechanism-based management of pain. Consequences of pain
      related to OA contribute to a substantial socioeconomic burden. 

PMID- 23973126
TI  - Risk factors associated with reduced work productivity among people with chronic
      knee pain.
AB  - OBJECTIVE: To determine the burden and risk factors associated with reduced work
      productivity among people with chronic knee pain. METHOD: A longitudinal study,
      nested within a randomised controlled trial (RCT) evaluating the long-term
      effects of dietary supplements, was conducted among people with chronic knee pain
      in paid employment (n = 360). Participants recorded days off work (absenteeism)
      and reduced productivity while at work (presenteeism) for seven days every two
      months over a 12-month period in a study specific diary. Examined risk factors
      included knee pain severity, occupational group, radiographic disease severity,
      physical activity, body mass index (BMI), health-related quality of life (SF-12)
      and co-morbidity. RESULTS: Over the 12-month follow up period, 50 (14%)
      participants reported one or more days off work due to knee problems, while 283
      (79%) reported reduced productivity while at work (presenteeism <100%). In
      multivariate analysis, the only significant risk factor for absenteeism was
      having an SF-12 Mental Component Summary (MCS) score <40 (OR: 2.49 [95% CI: 1.03
      5.98]). Significant risk factors for presenteeism included; reporting an; SF-12
      Physical Component Summary (PCS) score <50 (OR: 1.99 [95% CI: 1.05-3.76]), semi
      manual labour (OR: 2.23 [1.09-4.59]) or manual labour (OR: 6.40 [1.44-28.35]) or
      a high maximum knee pain (4-6 out of 10) (OR: 2.29 [1.17-4.46]). CONCLUSIONS:
      This longitudinal study found that among this cohort of people with chronic knee
      pain, the burden of reduced work productivity is mainly attributable to
      presenteeism rather absenteeism. This study demonstrated that effective
      strategies to increase work productivity should focus on reducing knee pain or
      physical disability especially among workers in manual or semi-manual labour.

PMID- 23973127
TI  - Structural correlates of pain in joints with osteoarthritis.
AB  - OBJECTIVE: To describe the insights on the epidemiology of pain-structure
      association and the ramifications of these studies for clinical trials. DESIGN:
      Narrative review summarizing the pertinent literature in this area, summarizing
      some of the methodologic challenges inherent and proposing some research
      initiatives to further understanding of this complex science. RESULTS: The
      predominant symptom in most patients presenting with osteoarthritis (OA) is pain.
      Over recent years a number of imaging based studies have narrowed the discord
      between structural findings on imaging and symptoms. The interpretation of pain
      in OA is still enigmatic and difficult to deal with both for clinicians and
      scientists. CONCLUSIONS: We would envisage that over the next few years many of
      the pressing questions pertaining to research into the structure pain
      relationship will continue to be addressed. With this, we can expect clinically
      appropriate therapeutic advance.

PMID- 23973128
TI  - The factors associated with pain severity in patients with knee osteoarthritis
      vary according to the radiographic disease severity: a cross-sectional study.
AB  - OBJECTIVES: Knee osteoarthritis (OA) pain is suggested to be associated with
      inflammation and detrimental mechanical loading across the joint. In this cross
      sectional study, we simultaneously examined the inflammation and alignment of the
      lower limb and examined how the pain components varied depending on the disease
      progression. DESIGN: One-hundred sixty female medial type of early- [n = 74 in
      Kellgren-Lawrence (K/L) 2] to advanced-stage (n = 96 in K/L >2) knee OA subjects
      (70.5 years on average) were enrolled. Knee pain was evaluated using a pain
      visual analog scale (VAS) and the pain-related subcategory of the Japanese Knee
      Osteoarthritis Measure (JKOM-pain). The serum interleukin (sIL)-6 level
      reflecting synovitis, and the high sensitivity C-reactive protein (hs-CRP) level
      were measured to evaluate the severity of inflammation. The anatomical axis angle
      (AAA) was measured as an alignment index. The beta-coefficient was estimated
      after adjusting for age and the body mass index (BMI) using a multiple linear
      regression analysis. RESULTS: Multiple linear regression analyses showed that the
      sIL-6 levels, but not AAA, associated with the pain VAS [beta = 10.77 (95%
      confidence interval (CI): 4.14-17.40), P < 0.01] and JKOM-pain scores [beta =
      3.19 (95% CI: 1.93-4.44), P < 0.001] in the early stage. Conversely, AAA, but not
      the sIL-6 levels, was found to be associated with the pain VAS [beta = -1.29 (95%
      CI: -2.51 to -0.08), P < 0.05] and JKOM-pain scores [beta = -0.49 (95% CI: -0.82
      to -0.16), P < 0.01] in the advanced stage. CONCLUSIONS: The presence of a higher
      level of sIL-6 and the varus alignment of the joint is associated with pain in
      early- and advanced-stage knee OA patients, respectively.

PMID- 23973129
TI  - Radiographic joint space width is correlated with 4-year clinical outcomes in
      patients with knee osteoarthritis: data from the osteoarthritis initiative.
AB  - OBJECTIVE: To evaluate if quantitative joint space width (JSW) measurements from
      radiographs correlate with 4-year Knee injury and Osteoarthritis Outcome Scores
      (KOOS) and clinical performance measures. METHOD: The study group consisted of
      942 patients with symptomatic knee osteoarthritis (OA). 4-year outcomes for six
      measures (KOOS Pain, Symptom, Quality of Life, and Function scores, 20-m walk
      pace, and chair stand time) were used to create six multiple linear regression
      models. Primary predictors were baseline minimum JSW and 4-year change in JSW
      measured from fixed flexion radiographs. Age, gender, body mass index (BMI),
      race, knee alignment, and baseline measures of the outcomes of interest were
      covariates. RESULTS: Lower baseline minimum JSW and a greater decrease in 4-year
      JSW significantly correlated with worse 4-year KOOS Pain, Symptom, and Quality of
      Life. With all other factors constant, a 4.1, 4.8, and 5.6 mm lower baseline JSW
      correlated with a clinically significant eight-point drop in 4-year KOOS Pain,
      Symptom, and Quality of Life scores respectively. Additionally, a 3.5, 3.1, and
      4.0 mm loss of JSW over 4 years correlated with a clinically significant eight
      point drop in 4-year KOOS Pain, Symptom, and Quality of Life scores respectively.
      CONCLUSIONS: Our results indicate quantitative radiographic JSW measurements
      correlate with 4-year clinical outcomes. Since patients with narrower JSW at the
      onset of study had lower KOOS scores at 4 years even after controlling for 4-year
      change in JSW and baseline KOOS scores, clinical outcomes in knee OA may be
      predetermined once the disease process begins. These findings suggest early
      treatment with disease modifying therapies may be necessary to influence
      outcomes.

PMID- 23973130
TI  - Cross-sectional and longitudinal associations between radiographic features and
      measures of pain and physical function in hand osteoarthritis.
AB  - OBJECTIVE: Previous longitudinal studies have shown no associations between
      increasing amount of radiographic hand osteoarthritis (OA) and levels of hand
      pain/disability. In this longitudinal study, we aimed to study whether
      radiographic hand OA was related to pain/disability in cross-sectional and
      longitudinal settings focusing on joint-specific analyses. METHODS: We included
      190 patients (173 women, mean (standard deviation, SD) age 61.5 (5.7) years) from
      the Oslo hand OA cohort, of whom 112 had 7-year follow-up data. Finger joints
      were scored for radiographic OA according to the Kellgren-Lawrence scale and
      Osteoarthritis Research Society International (OARSI) atlas. Pain and function
      were assessed by clinical examination (joint tenderness), grip strength and the
      Australian/Canadian (AUSCAN) questionnaire. Associations between radiographic
      hand OA and tenderness in the same joint were examined by logistic regression
      analyses with Generalized Estimating Equations, whereas associations between
      overall amount of radiographic OA and hand pain/disability were assessed by
      linear regression (adjusted for age and sex). RESULTS: A dose-dependent
      association was found between the severity of radiographic OA and tenderness in
      the same joint. Joints that progressed into severe radiographic OA during follow
      up had the highest odds of developing tenderness (OR = 11, 95% confidence
      interval (CI) 4.0-33). Incident erosions seemed to be the most important
      individual feature associated with incident tenderness (OR = 6.2, 95% CI 3.2-12).
      Weak associations were found between the amount of radiographic hand OA and
      overall hand pain/disability. CONCLUSION: Radiographic hand OA is associated with
      tenderness in the same joint, and erosive development strongly predicts future
      joint tenderness independent of other radiographic features.

PMID- 23973132
TI  - Association between bone marrow lesions detected by magnetic resonance imaging
      and knee pain in community residents in Korea.
AB  - OBJECTIVE: To describe the frequency of bone marrow lesions (BMLs) detected by
      magnetic resonance imaging (MRI), and to examine the association of BMLs with
      knee pain severity in community residents in Korea. METHODS: Participants were
      randomly chosen from the population-based Hallym Aging Study, irrespective of
      whether they had knee osteoarthritis (OA) or pain. Demographic and knee pain data
      were obtained by questionnaire. Radiographic evaluations consisted of weight
      bearing knee anteroposterior radiographs and 1.5-T MRI scans. MRI was performed
      in the dominant knees of subjects without knee pain and in the more symptomatic
      knees of subjects with knee pain. BMLs were graded according to the whole-organ
      MRI score. RESULTS: The mean age of the 358 study subjects was 71.8 years, and
      34.5% of subjects had radiographically detected knee OA. The prevalences of BMLs
      and large BMLs in the tibiofemoral compartments were 80.3% and 40.4%,
      respectively. After adjusting for age, sex, and body mass index, total and medial
      compartment BML scores were significantly associated with the presence of knee
      pain, and the association was stronger as the summary score for BML increased. In
      proportional regression analysis, knee pain severity increased with BML severity
      in any compartment and in the medial compartment. CONCLUSION: BMLs detected by
      MRI were highly prevalent in this elderly Asian population. BMLs were
      significantly linked to knee pain, and BML severity correlated with knee pain
      severity. BMLs may be important surrogate targets for monitoring pain and
      structure modification in OA therapeutics.

PMID- 23973131
TI  - Presence and extent of severe facet joint osteoarthritis are associated with back
      pain in older adults.
AB  - OBJECTIVE: To determine whether the presence and extent of severe lumbar facet
      joint osteoarthritis (OA) are associated with back pain in older adults,
      accounting for disc height narrowing and other covariates. DESIGN: Two hundred
      and fifty-two older adults from the Framingham Offspring Cohort (mean age 67
      years) were studied. Participants received standardized computed tomography (CT)
      assessments of lumbar facet joint OA and disc height narrowing at the L2-S1
      interspaces using four-grade semi-quantitative scales. Severe facet joint OA was
      defined according to the presence and/or degree of joint space narrowing,
      osteophytosis, articular process hypertrophy, articular erosions, subchondral
      cysts, and intraarticular vacuum phenomenon. Severe disc height narrowing was
      defined as marked narrowing with endplates almost in contact. Back pain was
      defined as participant report of pain on most days or all days in the past 12
      months. We used multivariable logistic regression to examine associations between
      severe facet joint OA and back pain, adjusting for key covariates including disc
      height narrowing, sociodemographics, anthropometrics, and health factors.
      RESULTS: Severe facet joint OA was more common in participants with back pain
      than those without (63.2% vs 46.7%; P = 0.03). In multivariable analyses,
      presence of any severe facet joint OA remained significantly associated with back
      pain (odds ratio (OR) 2.15 [95% confidence interval (CI) 1.13-4.08]). Each
      additional joint with severe OA conferred greater odds of back pain [OR per joint
      1.20 (95% CI 1.02-1.41)]. CONCLUSIONS: The presence and extent of severe facet
      joint OA on CT imaging are associated with back pain in community-based older
      adults, independent of sociodemographics, health factors, and disc height
      narrowing.

PMID- 23973133
TI  - Relationship between knee pain and the presence, location, size and phenotype of
      femorotibial denuded areas of subchondral bone as visualized by MRI.
AB  - OBJECTIVE: Conflicting associations between imaging biomarkers and pain in knee
      osteoarthritis (OA) have been reported. A relation between pain and denuded areas
      of subchondral bone (dABs) has been suggested and this study explores this
      relationship further by relating the presence, phenotype, location and size of
      dABs to different measures of knee pain. METHODS: 633 right knees from the
      Osteoarthritis Initiative (OAI) (250 men, age 61.7 +/- 9.6 yrs, BMI 29.4 +/- 4.7
      kg/m(2)) were included. Manual segmentation of the femorotibial cartilage plates
      was performed on 3 T coronal fast low angle shot with water excitation (FLASHwe)
      images. dABs were defined as areas where the subchondral bone was uncovered by
      cartilage. The following measures of pain were used: weightbearing-, non
      weightbearing-, moderate-to-severe-, infrequent- and frequent knee pain. RESULTS:
      Using pain measures from subjects without dABs as a reference, those with at
      least one dAB had a 1.64-fold higher prevalence ratio [PR, 95% confidence
      interval (CI) 1.24-2.18] to have frequent and 1.45-fold higher for moderate-to
      severe knee pain (95% CI 1.13-1.85). Subjects with dABs in central subregions had
      a 1.53-fold increased prevalence of having weightbearing pain (95% CI 1.20-1.97),
      especially when the central subregion was moderately (>10%) denuded (PR 1.81, 95%
      CI 1.35-2.42). Individuals with cartilage-loss-type dABs had a slightly higher
      prevalence (PR 1.13, 95% CI 1.00-1.27) of having frequent knee pain compared to
      individuals with intra-chondral-osteophyte-type dABs. CONCLUSION: This study
      supports a positive relation between femorotibial dABs and knee pain, especially
      when the dABs are located centrally (i.e., in weightbearing regions) or when the
      respective central subregion is moderately denuded.

PMID- 23973135
TI  - Mechanisms of the placebo response in pain in osteoarthritis.
AB  - INTRODUCTION: Administration of a placebo associates with symptomatic improvement
      in many conditions--the so-called placebo response. In this review we explain the
      concept of placebo response, examine the data that supports existence in
      osteoarthritis (OA), and discuss its possible mechanisms and determinants.
      METHODS: A Pubmed literature search was carried out. Key articles were
      identified, and their findings discussed in a narrative review. RESULTS: Pain,
      stiffness, self-reported function and physician-global assessment in OA clearly
      improve in response to placebo. However, more objective measures such as
      quadriceps strength and radiographic progression appear less responsive. Although
      not directly studied in OA, contextual effects, patient expectation and
      conditioning are believed to be the main mechanisms. Neurotransmitter changes
      that mediate placebo-induced analgesia include increased endogenous opioid
      levels, increased dopamine levels, and reduced levels of cholecystokinin. Almost
      all parts of the brain involved in pain processing are influenced during placebo
      induced analgesia. Determinants of the magnitude of placebo response include the
      patient-practitioner interaction, treatment response expectancy, knowledge of
      being treated, patient personality traits and placebo specific factors such as
      the route and frequency of administration, branding, and treatment costs.
      CONCLUSION: Clearer understanding of the neurobiology of placebo response
      validates its existence as a real phenomenon. Although routine administration of
      placebo for symptomatic improvement is difficult to justify, contextual factors
      that enhance treatment response should be employed in the management of chronic
      painful conditions such as OA where available treatments have only modest
      efficacy.

PMID- 23973134
TI  - Nerve growth factor: an update on the science and therapy.
AB  - OBJECTIVE: Nerve growth factor (NGF) is a key regulator of nociceptive pain and
      thus appears to be an interesting target molecule for an innovative class of
      analgesic medication. We set out to review the principles of neurogenic
      inflammation and results of anti-NGF regimens in animal studies as well as
      clinical trials with patients with back pain and osteoarthritis (OA). DESIGN: We
      searched using Google Scholar Search and Pubmed as well as through conference
      reports for articles and abstracts related to NGF and clinical trials using anti
      NGF regimens. We report on efficacy findings and adverse events (AEs) related to
      these agents in this review. RESULTS: We identified five full articles and eight
      abstract reports relating to anti-NGF agents studied for use in back pain and in
      OA. CONCLUSIONS: Anti-NGF agents either alone or in combination with non
      steroidal anti-inflammatory agents (NSAIDs) were more efficacious for the
      treatment of pain in a number of trials of knee and hip pain compared to NSAIDs
      alone. However, adverse effects that included rapidly progressive OA and joint
      replacement were more common in patients treated with anti-NGF and NSAIDs than
      either treatment alone. Anti-NGF treatment related neurologic symptoms including
      paresthesias, and potentially other types of adverse effects were usually
      transient but warrant additional investigation.

PMID- 23973136
TI  - Neuropathic pain symptoms on the modified painDETECT correlate with signs of
      central sensitization in knee osteoarthritis.
AB  - OBJECTIVE: Clinical tools are needed to identify and target a neuropathic-like
      phenotype, which may be associated with central sensitization (CS), in
      osteoarthritis (OA). The modified painDETECT questionnaire (mPD-Q) has face and
      content validity for identifying neuropathic-like symptoms in knee OA. To further
      validate the mPD-Q, this study assessed the unknown relationship between mPD-Q
      scores and signs of CS on quantitative sensory testing (QST) in knee OA. DESIGN:
      36 Individuals were recruited with chronic, symptomatic, knee OA without other
      pain/neurological conditions. Reference QST data were obtained from 18
      controls/32 eligible knees, enabling identification of sensory abnormalities/CS
      among case knees. A standardized questionnaire assessed psychological factors
      (depressive symptoms and pain catastrophizing), and for individual knees, mPD-Q
      and pain intensity scores. A standardized/comprehensive QST protocol was
      conducted for each knee. QST signs of CS were defined as: mechanical hyperalgesia
      and/or enhanced temporal summation and/or allodynia. The relationship between the
      presence of CS (yes/no) and a pre-selected mPD-Q score (<=12 or >12), by knees,
      was assessed using generalized estimating equations. RESULTS: Among 57 eligible
      case knees, 45.6% had >=1 sign of CS. Controlling for age, knees with higher mPD
      Q scores (>12.0) had higher odds of having QST signs of CS (adjusted odds ratio
      (OR) = 5.6; 95% confidence interval (CI), 1.3-22.9). This relationship was
      unaffected by controlling for depression and pain intensity, but was attenuated
      by pain catastrophizing. CONCLUSIONS: Among painful OA knees, higher mPD-Q scores
      were associated with greater odds of having signs of CS. Thus, the mPD-Q may aid
      the identification of CS in people with chronic knee OA.

PMID- 23973138
TI  - The association between pre-operative pain sensitisation and chronic pain after
      knee replacement: an exploratory study.
AB  - OBJECTIVE: Chronic pain after total knee replacement (TKR) is a prevalent
      condition, affecting about 20% of patients. The aim of this study was to explore
      the relationship between pre-operative pain thresholds and chronic pain after
      TKR. DESIGN: Patients listed for a TKR because of osteoarthritis participated in
      a Quantitative Sensory Testing (QST) session prior to surgery. Pressure pain
      thresholds (PPTs) and hot pain thresholds were assessed at the osteoarthritic
      knee and the forearm. Patients were followed-up at 1-year after TKR, and the
      severity of pain in the replaced knee was assessed using the WOMAC Pain score.
      Pre-operative median QST thresholds were compared to thresholds from a normative
      database collected from 50 people with no knee pain. The relationship between pre
      operative pain thresholds and pain severity post TKR were tested using
      correlations. RESULTS: Fifty-one patients participated in a pre-operative QST
      session and completed a 1-year WOMAC Pain score. Pre-operatively, patients
      demonstrated evidence of localised (knee) and widespread (forearm) pain
      sensitisation in response to pressure stimuli compared to healthy participants.
      Pre-operative PPTs at the forearm were found to be significantly correlated with
      1-year WOMAC Pain scores (r = 0.37, P = 0.008). CONCLUSIONS: This study provides
      preliminary evidence that pre-operative widespread pain sensitisation, measured
      using pressure algometry, may be associated with chronic pain after TKR. Further
      research is needed to explore the predictive value of an assessment of pre
      operative widespread pain sensitisation in identifying who is likely to develop
      chronic pain after TKR.

PMID- 23973137
TI  - Experimental pain sensitivity differs as a function of clinical pain severity in
      symptomatic knee osteoarthritis.
AB  - OBJECTIVE: Pain in knee osteoarthritis (OA) has historically been attributed to
      peripheral pathophysiology; however, the poor correspondence between objective
      measures of disease severity and clinical symptoms suggests that non-local
      factors, such as altered central processing of painful stimuli, also contribute
      to clinical pain in knee OA. Consistent with this notion, recent evidence
      demonstrates that patients with knee OA exhibit increased sensitivity to painful
      stimuli at body sites unaffected by clinical pain. DESIGN: In order to further
      investigate the contribution of altered pain processing to knee OA pain, the
      current study tested the hypothesis that symptomatic knee OA is associated with
      enhanced sensitivity to experimental pain stimuli at the knee and at remote body
      sites unaffected by clinical pain. We further anticipated that pain sensitivity
      would differ as a function of the OA symptom severity. Older adults with and
      without symptomatic knee OA completed a series of experimental pain assessments.
      A median split of the Western Ontario and McMaster Universities Index of
      Osteoarthritis (WOMAC) was used to stratify participants into low vs high OA
      symptom severity. RESULTS: Compared to controls and the low symptom group,
      individuals in the high symptom group were more sensitive to suprathreshold heat
      stimuli, blunt pressure, punctuate mechanical, and cold stimuli. Individuals in
      the low symptomatic OA group subgroup exhibited experimental pain responses
      similar to the pain-free group on most measures. No group differences in
      endogenous pain inhibition emerged. CONCLUSIONS: These findings suggest that
      altered central processing of pain is particularly characteristic of individuals
      with moderate to severe symptomatic knee OA.

PMID- 23973139
TI  - Acute postoperative pain following hospital discharge after total knee
      arthroplasty.
AB  - OBJECTIVE: The increasingly shorter hospitalization following total knee
      arthroplasty (TKA) requires patients to assume earlier responsibility to self
      manage their pain. Poorly managed acute pain increases the risk of persistent
      pain, reduces quality of life and increases unnecessary healthcare utilization.
      This study aims to examine post-discharge pain intensity, pain management
      behaviors and potential barriers to optimal self-management of pain. DESIGN: We
      administered a questionnaire at 2 weeks after discharge to 174 patients
      undergoing TKA in 10 Australian hospitals. Participants rated pain expectation
      and severity, use of analgesics and non-pharmacological methods, side-effects,
      walking and exercise times, perceptions of analgesics, adequacy of pain
      management information provided and satisfaction with pain relief. RESULTS: Of
      171 (98%) participants who completed the questionnaire, 88 (52%) reported that
      the worst pain period occurred during the first 2 weeks at home. During the first
      2 weeks at home, the average pain was 'severe/extreme' for 40 (23%) participants
      and 92 (54%) experienced severe pain at least some of the time. Many participants
      sought further medical help for their pain. Adequate information on analgesics
      and non-pharmacological methods for pain relief were reported by only 73% and
      47%, respectively. Approximately 20% had negative perceptions about analgesic
      use. Higher pain severity was associated with lower satisfaction and less time
      spent walking daily. CONCLUSIONS: Effective pain relief after hospital discharge
      following TKA is a challenge. Many participants reported significant pain, sought
      further medical help for pain relief and had inadequate information at discharge
      to effectively self-manage their postoperative knee pain.

PMID- 23973141
TI  - Altering foot progression angle in people with medial knee osteoarthritis: the
      effects of varying toe-in and toe-out angles are mediated by pain and
      malalignment.
AB  - OBJECTIVES: To evaluate if altering the foot progression angle (FPA) by varying
      magnitudes during gait alters the external knee adduction moment (KAM), knee
      flexion moment (KFM), knee extension moment (KEM) and/or symptoms in people with
      medial knee osteoarthritis (OA). Potential influence of pain and knee
      malalignment on load-modifying effects of FPA was investigated. DESIGN:
      Participants (n = 22) underwent 3-dimensional gait analysis to measure KAM peaks,
      KAM impulse, KFM and KEM peaks. Following natural gait, five altered FPA
      conditions were performed in random order (10 degrees  toe-in, 0 degrees  FPA, 10
      degrees  toe-out, 20 degrees  toe-out and 30 degrees  toe-out). A projection
      screen displayed their real-time FPA. Pain/discomfort at knees and feet/ankles
      were evaluated for each condition. Linear mixed models were used for statistical
      analysis. RESULTS: Toe-in reduced the early stance peak KAM and KEM but increased
      the KAM impulse, late stance peak and KFM. Toe-out reduced the KAM impulse, late
      stance peak and KFM (P < 0.001) but increased the early stance peak KAM and KEM.
      All effects were greater in participants with more varus knees. Pain
      significantly mediated the effect of altered FPA on the KAM impulse and late
      stance peak. In more painful individuals, toe-in was predicted to reduce the KAM
      impulse and late stance peak, and increase them for toe-out gait. There were no
      immediate symptomatic changes. CONCLUSIONS: Effects of altered FPA vary across
      all medial knee load parameters and it is difficult to determine an optimal
      direction of FPA change. Future studies should consider Western Ontario McMaster
      Universities OA Index (WOMAC) pain to judge the likely effects of altered FPA.

PMID- 23973140
TI  - Studies of pain management in osteoarthritis: bedside to policy.
AB  - OBJECTIVE: Osteoarthritis (OA) is a debilitating chronic condition requiring long
      term treatment of pain and functional impairment. Our objective was to
      characterize studies addressing management of OA-related pain with respect to the
      breadth of interventions, trial duration and size, outcome measures, and funding
      sources. DESIGN: We identified studies focused on 'pain' and 'osteoarthritis'
      from ClinicalTrals.gov and abstracted data on study status, sample size, design,
      funding source, duration, outcomes measured, and interventions evaluated. We
      examined associations among intervention type, funding source, sample size,
      duration, and outcomes measured. RESULTS: We identified 287 registered studies,
      of which 69% investigated pharmacologic interventions, 11% behavioral
      interventions, and 5% surgical procedures or devices, while the remainder
      examined other types of interventions. Eighty-seven percent evaluated knee OA.
      The average sample size was 290 subjects and average study duration was 7.4
      months, with 52% using durations <=3 months and 21% >=12 months. Industry funded
      64% of studies, either fully or partially. Of 180 completed studies, 139 were
      pharmacologic studies. Of these, 34 (24%) posted results to the registry. Among
      the studies funded by industry, 60% had durations <=3 months as compared with 36%
      among non-industry funded studies (P < 0.0001). Behavioral intervention trials
      tended to be of longer duration than pharmacologic trials and were less likely to
      be funded by industry. CONCLUSION: Over half of OA pain studies and >80% of those
      funded by industry used trial durations of less than 6 months. Future studies
      should take into consideration the need for long-term pain management for OA when
      designing trial protocols.

PMID- 23973142
TI  - Efficacy of low frequency pulsed subsensory threshold electrical stimulation vs
      placebo on pain and physical function in people with knee osteoarthritis:
      systematic review with meta-analysis.
AB  - OBJECTIVE: To determine if low frequency (<=100 Hz) pulsed subsensory threshold
      electrical stimulation produced either through pulsed electromagnetic field
      (PEMF) or pulsed electrical stimulation (PES) vs sham PEMF/PES intervention is
      effective in improving pain and physical function at treatment completion in
      adults with knee osteoarthritis (OA) blinded to treatment. METHOD: The relevant
      studies were identified by searching eight electronic databases and hand search
      of the past systematic reviews on the same topic till April 5, 2012. We included
      randomized controlled trials (RCTs) of people with knee OA comparing the outcomes
      of interest for those receiving PEMF/PES with those receiving sham PEMF/PES. Two
      reviewers independently selected studies, extracted relevant data and assessed
      quality. Pooled analyses were conducted using inverse-variance random effects
      models and standardized mean difference (SMD) for the primary outcomes. RESULTS:
      Seven small trials (459 participants/knees) were included. PEMF/PES improves
      physical function (SMD = 0.22, 95% confidence interval (CI) = 0.04, 0.41, P =
      0.02, I(2) = 0%), and does not reduce pain (SMD = 0.08, 95% CI = -0.17, 0.32, P =
      0.55, I(2) = 43%). The strength of the body of evidence was low for physical
      function and very low for pain. CONCLUSION: Current evidence of low and very low
      quality suggests that low frequency (<=100 Hz) pulsed subsensory threshold
      electrical stimulation produced either through PEMF/PES vs sham PEMF/PES is
      effective in improving physical function but not pain intensity at treatment
      completion in adults with knee OA blinded to treatment. Methodologically rigorous
      and adequately powered RCTs are needed to confirm the findings of this review.

PMID- 23973143
TI  - Acupuncture and other physical treatments for the relief of pain due to
      osteoarthritis of the knee: network meta-analysis.
AB  - OBJECTIVE: To compare the effectiveness of acupuncture with other relevant
      physical treatments for alleviating pain due to knee osteoarthritis. DESIGN:
      Systematic review with network meta-analysis, to allow comparison of treatments
      within a coherent framework. Comprehensive searches were undertaken up to January
      2013 to identify randomised controlled trials in patients with osteoarthritis of
      the knee, which reported pain. RESULTS: Of 156 eligible studies, 114 trials
      (covering 22 treatments and 9,709 patients) provided data suitable for analysis.
      Most trials studied short-term effects and many were classed as being of poor
      quality with high risk of bias, commonly associated with lack of blinding (which
      was sometimes impossible to achieve). End of treatment results showed that eight
      interventions: interferential therapy, acupuncture, TENS, pulsed electrical
      stimulation, balneotherapy, aerobic exercise, sham acupuncture, and muscle
      strengthening exercise produced a statistically significant reduction in pain
      when compared with standard care. In a sensitivity analysis of satisfactory and
      good quality studies, most studies were of acupuncture (11 trials) or muscle
      strengthening exercise (9 trials); both interventions were statistically
      significantly better than standard care, with acupuncture being statistically
      significantly better than muscle-strengthening exercise (standardised mean
      difference: 0.49, 95% credible interval 0.00-0.98). CONCLUSIONS: As a summary of
      the current available research, the network meta-analysis results indicate that
      acupuncture can be considered as one of the more effective physical treatments
      for alleviating osteoarthritis knee pain in the short-term. However, much of the
      evidence in this area of research is of poor quality, meaning there is
      uncertainty about the efficacy of many physical treatments.

PMID- 23973144
TI  - Increased pain sensitivity but normal function of exercise induced analgesia in
      hip and knee osteoarthritis--treatment effects of neuromuscular exercise and
      total joint replacement.
AB  - OBJECTIVE: To assess exercise induced analgesia (EIA) and pain sensitivity in hip
      and knee osteoarthritis (OA) and to study the effects of neuromuscular exercise
      and surgery on these parameters. DESIGN: The dataset consisted of knee (n = 66)
      and hip (n = 47) OA patients assigned for total joint replacement at Lund
      University Hospital undergoing pre-operative neuromuscular exercise and 43
      matched controls. Sensitivity to pressure pain was assessed by pressure algometry
      at 10 sites. Subjects were then instructed to perform a standardized static knee
      extension. Pressure pain thresholds (PPTs) were assessed at the contracting
      quadriceps muscle (Q) and at the resting deltoid muscle (D) before and during
      contraction. The relative increase in PPTs during contraction was taken as a
      measure of localized (Q) or generalized (D) EIA. Patients were assessed at
      baseline, following on average 12 weeks of neuromuscular exercise and 3 months
      following surgery. RESULTS: We found a normal function of EIA in OA patients at
      baseline. Previous studies have reported beneficial effects of physical exercise
      on pain modulation in healthy subjects. However, no treatment effects on EIA were
      seen in OA patients despite the increase in muscle strength following
      neuromuscular exercise and reduced pain following surgery. Compared to controls,
      OA patients had increased pain sensitivity and no beneficial effects on pain
      sensitivity were seen following treatment. CONCLUSIONS: To our knowledge, this is
      the first study of EIA in OA patients. Despite increased pain sensitivity, OA
      patients had a normal function of EIA.

PMID- 23973145
TI  - Osteoarthritis pain mechanisms: basic studies in animal models.
AB  - OBJECTIVE: Osteoarthritis (OA) is a complex and painful disease of the whole
      joint. At present there are no satisfying agents for treating OA. To promote OA
      research and improved treatment, this review summarizes current preclinical
      evidence on the development of OA. METHODS: Preclinical OA research was searched
      and key findings are summarized and commented. RESULTS: Mechanisms of OA
      associated pain have been studied in rodent knee OA models produced by intra-knee
      injection of the chondrocyte glycolytic inhibitor mono-iodoacetate (MIA),
      surgery, or spontaneous development in some species. These models are clinically
      relevant in terms of histological damage and functional changes, and are used to
      study mechanisms underlying mechanical, thermal, ambulatory, body weight
      supporting-evoked, and ongoing OA pain. Recent peripheral, spinal, and
      supraspinal biochemical and electrophysiological studies in these models suggest
      that peripheral pro-inflammatory mediators and neuropeptides sensitize knee
      nociceptors. Spinal cytokines and neuropeptides promote OA pain, and peripheral
      and spinal cannabinoids inhibit OA pain respectively through cannabinoid-1 (CB1)
      and CB1/CB2 receptors. TRPV1 and metalloproteinases contribute and supraspinal
      descending facilitation of 5-hydroxytryptamine (5-HT)/5-HT 3 receptors may also
      contribute to OA pain. Conditioned place preference tests demonstrate that OA
      pain induces aversive behaviors, suggesting the involvement of brain. During OA,
      brain functional connectivity is enhanced, but at present it is unclear how this
      change is related to OA pain. CONCLUSION: Animal studies demonstrate that
      peripheral and central sensitization contributes to OA pain, involving
      inflammatory cytokines, neuropeptides, and a variety of chemical mediators.
      Interestingly, brainstem descending facilitation of 5-HT/5-HT3 receptors plays a
      role OA pain.

PMID- 23973147
TI  - Spinal nociceptive reflexes are sensitized in the monosodium iodoacetate model of
      osteoarthritis pain in the rat.
AB  - OBJECTIVE: Evidence suggests that osteoarthritis (OA) is associated with altered
      central pain processing. We assessed the effects of experimentally induced OA on
      the excitability of spinal nociceptive withdrawal reflexes (NWRs), and their
      supraspinal control in a preclinical OA model. DESIGN: Experimental OA was
      induced in rats with knee injection of monosodium iodoacetate (MIA) and pain
      behaviour was assessed. 14/28 days post-MIA or saline injection, rats were
      anaesthetised for spinal NWR recording from tibialis anterior (TA) and biceps
      femoris (BF) hind limb muscles during plantar hind paw stimulation. Thresholds,
      receptive field sizes and wind up (incremental increase to repetitive
      stimulation) were measured in intact (d14/28) and spinalised (severed spinal
      cord; d28) MIA- and saline-injected rats. RESULTS: MIA reduced BF mechanical
      thresholds at day 28. Spinalisation of MIA rats did not prevent this
      hyperexcitability, and failed to produce the reduction in reflex receptive field
      (RRF) size observed in saline rats. These data indicate that MIA induces a
      hyperexcitability of BF NWR circuits that is maintained at the spinal level. In
      contrast, MIA appeared to have no effect on NWRs evoked by mechanical stimuli in
      the ankle flexor TA in intact rats, however spinalisation revealed
      hyperexcitability. Thus, 28 days following MIA-treatment, descending supraspinal
      inhibition normalised TA NWRs and was only overcome following repetitive noxious
      stimulation during wind up. CONCLUSIONS: We demonstrate that spinal nociceptive
      reflex pathways are sensitized following the development of OA, suggesting the
      presence of central sensitization. Further, our data reflect OA-induced
      alterations in the descending control of reflex responses. Our findings
      contribute to a mechanism-based understanding of OA pain.

PMID- 23973146
TI  - A commentary on modelling osteoarthritis pain in small animals.
AB  - OBJECTIVE: To describe the currently used animal models for the study of
      osteoarthritis (OA) pain, with an emphasis on small animals (predominantly mice
      and rats). OUTLINE: Narrative review summarizing the opportunities and
      limitations of the most commonly used small animal models for the study of pain
      and pain pathways associated with OA, and discussing currently used methods for
      pain assessment. Involvement of neural degeneration in OA is briefly discussed. A
      list of considerations when studying pain-related behaviours and pathways in
      animal models of OA is proposed. CONCLUSIONS: Animal models offer great potential
      to unravel the complex pathophysiology of OA pain, its molecular and temporal
      regulation. They constitute a critical pathway for developing and testing disease
      specific symptom-modifying therapeutic interventions. However, a number of issues
      remain to be resolved in order to standardize pre-clinical OA pain research and
      to optimize translation to clinical trials and patient therapies.

PMID- 23973148
TI  - Differences in structural and pain phenotypes in the sodium monoiodoacetate and
      meniscal transection models of osteoarthritis.
AB  - OBJECTIVES: To characterize differences in joint pathology and pain behavior
      between two rat models of osteoarthritis (OA) in order to inform selection of
      animal models for interventional studies. METHOD: Knee OA was induced in Sprague
      Dawley rats by either meniscal transection (MNX) or intra-articular injection of
      monosodium iodoacetate (MIA). Controls were subjected to sham surgery or saline
      injection. In a separate experiment, a single intra-articular injection of
      triamcinolone acetonide was administered 14 days after MNX or MIA arthritis
      induction. Pain behavior and joint pathology were quantified. RESULTS: Both
      models displayed synovial inflammation, chondropathy and osteophytosis.
      Chondropathy scores increased with time similarly in the two models. Inflammation
      and osteophyte scores were greater in MNX model compared to the MIA model. At day
      49, the MNX model exhibited a greater number of channels crossing the
      osteochondral junction compared to all other groups. The MNX model exhibited
      greater weight bearing asymmetry compared to the MIA model, whereas the MIA model
      displayed more consistent hindpaw allodynia. Triamcinolone attenuated weight
      bearing asymmetry and distal allodynia to control levels in the MNX model, but
      distal allodynia was unaltered in the MIA model. CONCLUSIONS: The comparison of
      the two models of OA in rats, using identical assessment tools has demonstrated
      that although both models display features of OA, there are differences between
      the models which may represent different aspects of human OA. Thus, model
      selection should be based on the pathological aspects of OA under investigation.

PMID- 23973149
TI  - Blockade of nociceptive sensory afferent activity of the rat knee joint by the
      bradykinin B2 receptor antagonist fasitibant.
AB  - OBJECTIVE: The aim of this study was to determine in intact and inflamed knee
      joints of the rat, the effect of the bradykinin (BK) B2 receptor antagonist
      fasitibant (MEN16132) on nociceptor mechanosensitivity and hyperalgesia. METHODS:
      Joint afferent sensory fibers of the medial articular nerve of anesthetized
      animals were electrophysiologically recorded, measuring nerve impulse activity
      evoked by passive innocuous and noxious movements of the joint, in intact and
      kaolin and carrageenan-injected joints. Knee joints of rats were also acutely
      inflamed by intra-articular injection of carrageenan alone. Long term duration of
      fasitibant antinociceptive effects were behaviorally evaluated using the
      incapacitance test. RESULTS: BK (100 MUM) injected into the saphenous artery,
      induced excitation and sensitization of multi- and single unit recordings.
      Fasitibant (300 MUM) injected prior to BK, reduced its excitatory effects as well
      as the overall increase of movement-evoked activity resulting from repeated
      injections of BK. Fasitibant did not affect movement-evoked activity of sensory
      fibers of intact, non-inflamed knee joints. Intra-articular fasitibant (100
      MUg/knee) significantly reduced the carrageenan-induced inflammatory hyperalgesia
      measured with the incapacitance test up to four days after treatment. This
      antinociceptive effect was not obtained with systemic endovenous injection of the
      drug. CONCLUSIONS: Fasitibant prevents B2 receptor-mediated activation and
      sensitization of peripheral joint afferents and the ensuing inflammatory
      hyperalgesia, and may be a useful, novel drug for arthritis pain treatment.

PMID- 23973150
TI  - Pain, motor and gait assessment of murine osteoarthritis in a cruciate ligament
      transection model.
AB  - OBJECTIVE: The major complaint of Osteoarthritis (OA) patients is pain. However,
      due to the nature of clinical studies and the limitation of animal studies, few
      studies have linked function impairment and behavioral changes in OA animal
      models to cartilage loss and histopathology. Our objective was to study surrogate
      markers of functional impairment in relation to cartilage loss and pathological
      changes in a post-traumatic mouse model of OA. METHOD: We performed a battery of
      functional analyses in a mouse model of OA generated by cruciate ligament
      transection (CLT). The changes in functional analyses were linked to histological
      changes graded by OARSI standards, histological grading of synovitis, and
      volumetric changes of the articular cartilage and osteophytes quantified by phase
      contrast micro-computed tomography (MUCT). RESULTS: OA generated by CLT led to
      decreased time on rotarod, delayed response on hotplate analysis, and altered
      gait starting from 4 weeks after surgery. Activity in open field analysis did not
      change at 4, 8, or 12 weeks after CLT. The magnitude of behavioral changes was
      directly correlated with higher OARSI histological scores of OA, synovitis in the
      knee joints, cartilage volume loss, and osteophyte formation. CONCLUSION: Our
      findings link functional analyses to histological grading, synovitis,
      comprehensive three-dimensional assessment of cartilage volume and osteophyte
      formation. This serves as a reference for a mouse model in predicting outcomes of
      OA treatment.

PMID- 23973151
TI  - Intra-articular anaesthesia mitigates established pain in experimental
      osteoarthritis: a preliminary study of gait impulse redistribution as a biomarker
      of analgesia pharmacodynamics.
AB  - OBJECTIVE: Develop a sensitive, functional biomarker of persistent joint pain in
      a large animal model of experimental osteoarthritis. Evaluate Impulse Ratio as a
      measure of weight distribution among supporting limbs throughout the early
      natural history of osteoarthritis and with local anaesthesia and analgesia.
      DESIGN: The distribution of weight bearing in the trot of 11 skeletally-mature
      dogs was analyzed before and after unilateral surgical intervention (cranial
      cruciate transection or distal femoral focal impact). The short-term effects of
      two analgesic treatments (intra-articular lidocaine and intra-dermal meloxicam)
      were then evaluated as an index of pain relief based on the redistribution of
      weight-bearing impulse between normal and injured limbs. RESULTS: Impulse Ratio
      was able to resolve weight redistribution between limbs in both long-term (weekly
      for over 400 days) and short-term (15 min intervals) joint evaluations. Joint
      pain relief from lidocaine administration could be reliably tracked over its
      brief acting time course. Meloxicam administration resulted in ambiguous results,
      where average weight bearing in the injured limb did not increase, but the
      variability of limb use changed transiently and reversibly. CONCLUSION: Joint
      function and the role of persistent joint pain in the development of
      osteoarthritis can be investigated effectively and efficiently in a large animal
      model through the use of Impulse Ratio. Impulse Ratio can be a functionally
      relevant and sensitive biomarker of locomotion-related joint pain.

PMID- 23973153
TI  - The innervation of synovium of human osteoarthritic joints in comparison with
      normal rat and sheep synovium.
AB  - OBJECTIVE: To study whether osteoarthritis (OA) in the knee is associated with a
      change of the innervation pattern in the synovial layer. DESIGN: In synovial
      tissue from the normal knee joint of rat and sheep we studied the presence of
      vessels and of nerve fibres using transmission electron microscopy and
      immunohistochemistry. Synovial material was also obtained from patients who
      underwent total knee replacement surgery. This material was examined for
      inflammatory changes, and the presence of vessels and nerve fibres was assessed.
      RESULTS: The synovium in the parapatellar region of the normal knee joint of rat
      and sheep exhibited a dense capillary and neuronal network. It was entered by
      calcitonin gene-related peptide containing sensory fibres and tyrosine
      hydroxylase-positive sympathetic nerve fibres. Synovial material from patients
      with knee OA exhibited different degrees of inflammation. Synovial material
      without inflammation exhibited a similar vascular and neuronal network as the
      normal knee joint from rat and sheep. However, in synovium with inflammatory
      changes we found a significant decrease of nerve fibres in depth ranges close to
      the synovial lining layer depending on the degree of inflammation whereas deeper
      regions were less affected. CONCLUSIONS: Inflammatory changes in the synovium of
      OA joints are associated with a massive destruction of the capillary and neuronal
      network which is present in normal synovium. Due to the disappearance of the
      sensory fibres it is unlikely that OA pain is initiated directly in the synovium.
      The loss of normally innervated vascularisation may have multiple consequences
      for the physiological functions of the synovium.

PMID- 23973152
TI  - Genomics of pain in osteoarthritis.
AB  - Osteoarthritis (OA) accounts for the majority of the disease burden for
      musculoskeletal disorders and is one of the leading causes of disability
      worldwide. This disability is the result not of the cartilage loss that defines
      OA radiographically, but of the chronic pain whose presence defines symptomatic
      OA. It is becoming clear that many genes, each with a small effect size,
      contribute to the risk of developing OA. However, the genetics of OA pain are
      only just starting to be explored. This review will describe the first genes to
      have been identified in genomic studies of OA pain, as well as the possible dual
      roles of genes previously identified in genomic studies of OA in the context of
      pain. Difficulties associated with attempting to characterise the genetics of OA
      pain will be discussed and promising future avenues of research into genetic and
      epigenetic factors affecting OA pain described. 

PMID- 23973154
TI  - The influence of synovial inflammation and hyperplasia on symptomatic outcomes up
      to 2 years post-operatively in patients undergoing partial meniscectomy.
AB  - OBJECTIVE: Synovitis is associated with pain and other symptoms in patients with
      knee osteoarthritis (OA), and in patients with meniscal tears even in the absence
      of radiographic OA. Patients undergoing arthroscopic partial meniscectomy were
      followed for 2 years to determine whether synovitis predicts post-operative
      symptoms. DESIGN: Thirty-three patients scheduled for arthroscopy were recruited
      for this pilot study. Symptoms were assessed using a knee pain scale, the Lysholm
      score, and the short form-12 (SF-12((r))) pre-operatively and at 16 weeks, 1 year
      and 2 years post-operatively. Synovial inflammation and hyperplasia were graded
      on surgical biopsies. Linear mixed effects models were tested to determine
      whether inflammation or hyperplasia is associated with outcome scores over time.
      RESULTS: Lysholm scores and SF-12((r)) physical component sub-scores were worse
      pre-operatively in patients with inflammation (Lysholm: 52.42 [95% confidence
      interval (CI) 42.37, 62.47] vs 72.38 [66.03, 78.72], P < 0.001; SF-12: 36.81
      [28.26, 45.37] vs 46.23 [40.14, 52.32], P < 0.05). Up to 2-years post
      operatively, patients with inflammation achieved mean scores similar to those
      without inflammation. As a result, the mean improvement in Lysholm scores was
      13.01 [1.48-24.53] points higher than patients without inflammation, P = 0.03.
      33% (4/12) of patients with inflammation still had fair to poor Lysholm scores 2
      years after surgery compared to 7% (1/15, P=0.14) without inflammation. No
      association between hyperplasia and symptoms was noted. CONCLUSIONS: In this
      pilot study of patients undergoing partial meniscectomy, synovial inflammation
      was associated with worse pre-operative symptoms, but not with poorer outcomes in
      the first 2 years post-arthroscopy. Larger cohorts and longer follow-up should be
      pursued to confirm this relationship, and determine if the initial response is
      sustained.

PMID- 23973157
TI  - What axons tell each other: axon-axon signaling in nerve and circuit assembly.
AB  - A remarkable feature of nervous system development is the ability of axons
      emerging from newly formed neurons to traverse, by cellular scale, colossal
      distances to appropriate targets. The earliest axons achieve this in an
      essentially axon-free environment, but the vast majority of axons eventually grow
      along a scaffold of nerve tracts created by earlier extending axons. Signal
      exchange between sequentially or simultaneously extending axons may well
      represent the predominant mode of axonal navigation, but proportionally few
      efforts have so far been directed at deciphering the underlying mechanisms. This
      review intends to provide a conceptual update on the cellular and molecular
      principles driving axon-axon interactions, with emphasis on those contributing to
      the fidelity of axonal navigation, sorting and connectivity during nerve and
      circuit assembly. 

PMID- 23973155
TI  - The effects of nonsteroidal anti-inflammatory drugs on clinical outcomes,
      synovial fluid cytokine concentration and signal transduction pathways in knee
      osteoarthritis. A randomized open label trial.
AB  - OBJECTIVE: We investigated the effects of celecoxib, diclofenac, and ibuprofen on
      the disease-specific quality of life, synovial fluid cytokines and signal
      transduction pathways in symptomatic knee osteoarthritis (OA). DESIGN: Ninety
      patients scheduled for a total knee arthroplasty (TKA) were randomized to six
      groups that were treated with low and high dosages of celecoxib, diclofenac or
      ibuprofen. At the time of the first admission (T0) and at surgery (T1 = 14 days
      after beginning of the nonsteroidal anti-inflammatory drugs (NSAIDs)), samples of
      knee synovial fluid were obtained from each patient for analysis. During the
      surgery the synovial tissue was harvested from the knee of patients. The Western
      Ontario and McMaster universities (WOMAC) score was used to evaluate the patient
      disease-specific quality of life at T0 and T1. Microarray tests performed at T0
      and T1 were used to evaluate the effects of NSAIDs on Tumor necrosis factor (TNF)
      alpha, Interleukin-6 (IL-6), IL8 and Vascular endothelial growth factor (VEGF)
      concentration in the synovial fluid. Western blot assays evaluated the effects of
      NSAIDs on MAP kinase (MAPK) signal transduction pathway in the synovial membrane.
      RESULTS: NSAID treatment induced a statistically significant improvement in the
      WOMAC score and a statistically significant decrease in the IL-6, VEGF and TNF
      alpha concentration in the synovial fluid. Higher dosages of NSAIDs provided a
      greater improvement in the disease-specific quality of life of patients and lower
      concentrations of pro-inflammatory cytokines in the synovial fluid. Inhibition of
      MAPKs was noted after NSAID treatment. CONCLUSION: Short-term NSAID treatment
      improves the patient disease-specific quality of life with a parallel decrease in
      pro-inflammatory synovial fluid cytokine levels in knee OA. Signal transduction
      pathways may be involved in regulating the anti-inflammatory effects of NSAIDs.
      ClinicalTrial.gov: NCT01860833.

PMID- 23973156
TI  - LIS1 functions in normal development and disease.
AB  - LIS1, the first gene to be identified as involved in a neuronal migration
      disease, is a dosage-sensitive gene whose proper levels are required for multiple
      aspects of cortical development. Deletions in LIS1 result in a severe brain
      malformation, known as lissencephaly, whereas duplications delay brain
      development. LIS1 affects the proliferation of progenitors, spindle orientation
      and interkinetic nuclear movement in the ventricular zone, as well as
      nucleokinesis and migration of neurons. LIS1 regulatory interaction with the
      minus end directed molecular motor cytoplasmic dynein is the key for
      understanding its complex cellular functions. LIS1-dynein interaction decreases
      the average velocity of the molecular motor in vitro, shows more complex effects
      in vivo, and may be of importance in high-load transport especially in neurons. 

PMID- 23973158
TI  - Transcriptional coupling of neuronal fate commitment and the onset of migration.
AB  - During mammalian CNS development, when the neural precursor cells commit to the
      neuronal fate they must delaminate and migrate toward the pial surface in order
      to reach the appropriate final location. Thus, the coordination of delamination
      and fate commitment is important in creating the correct structure. Although
      previous studies have proposed that spindle orientation during mitosis plays a
      role in both delamination and fate commitment, thus coordinating these events,
      subsequent studies have challenged this model. Recent work has identified several
      transcriptional mechanisms associated with neurogenesis that inhibit cell
      adhesion of newborn neurons and intermediate neuronal progenitors, thereby
      triggering delamination and linking it with fate commitment. 

PMID- 23973159
TI  - In vitro effects of lidocaine on contractility of circular and longitudinal
      equine intestinal smooth muscle.
AB  - The purpose of the study was to compare the contractility-enhancing effects of
      lidocaine in equine jejunal circular (CSM) and longitudinal smooth muscle (LSM)
      in vitro. In previous studies, more pronounced effects of lidocaine were observed
      in ischaemia-reperfusion (IR) injured smooth muscle. Therefore in this study,
      effects were examined in both non-injured control tissues and tissues challenged
      by a defined, artificial IR injury. Isometric contractile performance of CSM and
      LSM, assessed by frequency (F), amplitude (A) and mean active force (MAF) of
      contractions, was defined as contractility. LSM featured lower basic
      contractility compared to CSM. Lidocaine provoked contractility-enhancing effects
      in both smooth muscle layers, but except for F at high lidocaine concentrations,
      contractility of LSM remained lower throughout the trial. Additionally, higher
      lidocaine concentrations were required to cause significant effects in LSM. No
      differences were observed in contractility of control and IR injured smooth
      muscle, but higher lidocaine concentrations were needed to provoke effects in IR
      injured smooth muscle. In contrast to CSM, contractility of LSM did not decrease
      at comparably high lidocaine concentrations. Differences in basic contractility
      of CSM and LSM might be explained by physiologically lower activity of LSM per se
      or by a thinner LSM layer with fewer smooth muscle cells taking part in
      contractions. The smaller thickness of the LSM layer may also contribute to
      persisting discrepancies in contractility following lidocaine application.
      Additionally, variations in lidocaine concentrations necessary for inducing
      significant effects could result from differences in the molecular structure of
      CSM and LSM cells. 

PMID- 23973160
TI  - Young Friesian horses show familial aggregation in fitness response to a 7-week
      performance test.
AB  - The aim of this study was to monitor the fitness level of young Friesian horses
      and to assess whether fitness data are predictive for final performance score and
      whether familial aggregation of response to training could be detected. Sixty-six
      young Friesian horses, the offspring of six different stallions (A, B, C, D, E
      and F), underwent a 7-week performance test. The horses were given a performance
      score for their ability for dressage (in weeks 5 and 7; 0-110 points) and were
      evaluated for fitness using standardised exercise tests (SETs) at the beginning
      (week 2, SET-I) and the end (week 6, SET-II) of the period. Heart rate (HR,
      beats/min) was measured in both SETs, and plasma lactate concentration (LA,
      mmol/L) was measured only in SET-II. Fitness of the horses improved moderately
      but significantly between SET-I and SET-II (P=0.015). There was a large
      heterogeneity in responsiveness to training; some horses were high responders,
      whereas others were non- or low responders. There was a familial aggregation of
      HR canter-1 response to training (P=0.039), while the HR of stallion C's
      offspring decreased significantly more than those of stallions A (P=0.09), D
      (P=0.013) and F (P=0.009). Horses that were reluctant to exercise did not differ
      in HR or LA concentrations compared to those that completed the SET, which may
      have been a sign of overreaching. HR had no predictive value for the performance
      score, but horses that did not reach the anaerobic threshold in SET-II scored
      significantly better (73.8 +/- 5.6 points) than horses that did not (69.9 +/- 5.9
      points, P=0.025). The findings demonstrate for the first time in the horse a
      familial aggregation of HR response to training, as has been reported previously
      in humans. Familial aggregation suggests a genetic influence on the effect of
      training on fitness in horses. HR could not predict final performance score, but
      LA concentrations during SET-II were predictive.

PMID- 23973161
TI  - First-line radiofrequency ablation with or without artificial ascites for
      hepatocellular carcinomas in a subcapsular location: local control rate and risk
      of peritoneal seeding at long-term follow-up.
AB  - AIM: To compare the long-term local control of hepatocellular carcinoma (HCC) and
      risk of peritoneal seeding via percutaneous radiofrequency ablation (RFA) using
      artificial ascites with those of RFA without artificial ascites. MATERIALS AND
      METHODS: The Institutional Review Board approved this retrospective study. From
      April 2005 to February 2008, 160 patients (121 men, 39 women; age range 36-79
      years) with a single subcapsular HCC (mean size 2.19 cm) were treated with
      ultrasonography-guided percutaneous RFA as a first-line therapy. Forty-four
      patients were treated with RFA using artificial ascites, whereas the other 116
      patients were treated without artificial ascites. The cumulative local tumour
      progression (LTP) and peritoneal seeding were compared in both groups using
      follow-up computed tomography (CT). Cumulative LTP rates were analysed using the
      Kaplan-Meier method and the log-rank test. Risk of peritoneal seeding was
      investigated by means of multivariate analysis. RESULTS: The overall median
      follow-up period was 52.5 months (range 13-76 months). The 1, 2, 4, and 6 year
      cumulative LTP rates were 17.1, 27.6, 35.2, and 35.2%, respectively, in the group
      with artificial ascites, and 8, 15.2, 26.6, and 34.4% in the group without
      artificial ascites, without significant difference (p = 0.332). The rates of
      peritoneal seeding were 6.8% (3/44) in the group with artificial ascites and 2.6%
      (3/116) in the group without artificial ascites, a non-significant difference (p
      = 0.347). The biopsy prior to RFA was the independent risk factor of peritoneal
      seeding regardless of the use of artificial ascites. CONCLUSION: Long-term local
      tumour control and risk of peritoneal seeding were comparable for RFA with or
      without artificial ascites when used as a first-line therapy for subcapsular HCC.

PMID- 23973162
TI  - Commentary on discrepancies in discrepancy meetings.

PMID- 23973163
TI  - Differentiation between active and chronic Crohn's disease using MRI small-bowel
      motility examinations - initial experience.
AB  - AIM: To evaluate the influence of locally active Crohn's disease on systemic
      small-bowel motility in patients with chronic Crohn's disease compared to healthy
      individuals. MATERIAL AND METHODS: Fifteen healthy individuals (11 men, four
      women; mean age 37 years) and 20 patients with histopathologically proven active
      (n = 15; 10 women, 5 men; mean age 45 years) or chronic (n = 5; four women, one
      man; mean age 48 years) Crohn's disease were included in this institutional
      review board-approved, retrospective study. Magnetic resonance imaging (MRI; 1.5
      T) was performed after standardized preparation. Two-dimensional (2D) cine
      sequences for motility acquisition were performed in apnoea (27 s). Motility
      assessment was performed using dedicated software in three randomly chosen areas
      of the small-bowel outside known Crohn's disease-affected hotspots. The main
      quantitative characteristics (frequency, amplitude, occlusion rate) were compared
      using Student's t-test and one-way analysis of variance (ANOVA). RESULTS: Three
      randomly chosen segments were analysed in each participant. Patients with active
      Crohn's disease had significantly (p < 0.05) reduced contraction frequencies
      (active Crohn's disease: 2.86/min; chronic: 4.14/min; healthy: 4.53/min) and
      luminal occlusion rates (active: 0.43; chronic: 0.70; healthy: 0.73) compared to
      healthy individuals and patients with chronic Crohn's disease. Contraction
      amplitudes were significantly reduced during active Crohn's disease (6.71 mm)
      compared to healthy participants (10.14 mm), but this only reached borderline
      significance in comparison to chronic Crohn's disease (8.87 mm). Mean bowel lumen
      diameter was significantly (p = 0.04) higher in patients with active Crohn's
      disease (16.91 mm) compared to healthy participants (14.79 mm) but not in
      comparison to patients with chronic Crohn's disease (13.68). CONCLUSION: The
      findings of the present study suggest that local inflammatory activity of small
      bowel segments in patients with active Crohn's disease alters small-bowel
      motility in distant, non-affected segments. The motility patterns revealed
      reduced contraction-wave frequencies, amplitudes, and decreased luminal occlusion
      rates. Thus evaluation of these characteristics potentially helps to
      differentiate between chronic and active Crohn's disease.

PMID- 23973165
TI  - Yeast haspin kinase regulates polarity cues necessary for mitotic spindle
      positioning and is required to tolerate mitotic arrest.
AB  - Haspin is an atypical protein kinase that in several organisms phosphorylates
      histone H3Thr3 and is involved in chromosome segregation. In Saccharomyces
      cerevisiae, H3Thr3 phosphorylation has never been observed and the function of
      haspin is unknown. We show that deletion of ALK1 and ALK2 haspin paralogs causes
      the mislocalization of polarisome components. Following a transient mitotic
      arrest, this leads to an overly polarized actin distribution in the bud where the
      mitotic spindle is pulled. Here it elongates, generating anucleated mothers and
      binucleated daughters. Reducing the intensity of the bud-directed pulling forces
      partially restores proper cell division. We propose that haspin controls the
      localization of polarity cues to preserve the coordination between polarization
      and the cell cycle and to tolerate transient mitotic arrests. The evolutionary
      conservation of haspin and of the polarization mechanisms suggests that this
      function of haspin is likely shared with other eukaryotes, in which haspin may
      regulate asymmetric cell division.

PMID- 23973164
TI  - The Drosophila selectin furrowed mediates intercellular planar cell polarity
      interactions via frizzled stabilization.
AB  - Establishment of planar cell polarity (PCP) in a tissue requires coordination of
      directional signals from cell to cell. It is thought that this is mediated by the
      core PCP factors, which include cell-adhesion molecules. Here, we demonstrate
      that furrowed, the Drosophila selectin, is required for PCP generation.
      Disruption of PCP in furrowed-deficient flies results from a primary defect in Fz
      levels and cell adhesion. Furrowed localizes at or near apical junctions, largely
      colocalizing with Frizzled and Flamingo (Fmi). It physically interacts with and
      stabilizes Frizzled, and it mediates intercellular Frizzled-Van Gogh
      (Vang)/Strabismus interactions, similarly to Fmi. Furrowed does so through a
      homophilic cell-adhesion role that is distinct from its known carbohydrate
      binding function described during vertebrate blood-cell/endothelial cell
      interactions. Importantly, the carbohydrate function is dispensable for PCP
      establishment. In vivo studies suggest that Furrowed functions partially
      redundantly with Fmi, mediating intercellular Frizzled-Vang interactions between
      neighboring cells.

PMID- 23973166
TI  - Venous thromboembolism after shoulder arthroplasty: a systematic review.
AB  - BACKGROUND: Shoulder arthroplasty (SA) is a common orthopaedic procedure that is
      being performed on a more and more frequent basis. Venous thromboembolism (VTE)
      as a complication has received little attention when it occurs after SA. The
      literature lacks a comprehensive summary of the incidence, risk factors, and
      prophylaxis of VTE in this population of patients. METHODS: Literature on VTE
      after SA has been identified from 5 scientific databases: EMBASE, MEDLINE, Web of
      Science, CINAHL, and Cochrane. All primary full-text articles reporting at least
      1 case of deep vein thrombosis or pulmonary embolism after SA were included.
      Articles were critically appraised and systematically analyzed to determine the
      incidence, risk factors, thromboprophylaxis, diagnosis, and management of VTE
      after SA. RESULTS: This study included 14 articles. The reported incidence of VTE
      after SA was 0.2% to 16.0%. The most serious risk factors for development of VTE
      included history of VTE, thrombophilia, major surgery, advanced age, current
      malignant disease, immobility, and bed confinement. Diagnosis was typically
      determined by duplex scan and chest computed tomography scan. VTE prophylaxis was
      used in 6 (43%) of the included studies, with the ideal method of prophylaxis
      unknown. CONCLUSIONS: Although variability exists in the reported incidence of
      VTE, surgeons should still be aware of the potential for this serious
      complication after SA. We recommend assessing the risk factors and estimating the
      VTE risk status for all patients undergoing SA. The ideal method of prophylaxis
      for this population of patients remains unknown and should be investigated in
      future high-quality clinical studies.

PMID- 23973167
TI  - Microparticle-associated tissue factor activity in patients with metastatic
      pancreatic cancer and its effect on fibrin clot formation.
AB  - Highly elevated microparticle (MP)-associated tissue factor (TF) activity was
      found in patients with pancreatic cancer, one of the most prothrombotic
      malignancies. It remains to be elucidated whether MP-TF activity reflects the
      prothrombotic state in these patients. MP-TF activity levels and the TF-dependent
      and -independent effect of MPs on fibrin clot formation were determined in
      patients with metastatic pancreatic cancer (n = 27), in healthy individuals (n =
      10) and in plasma samples from lipopolysaccharide (LPS)-stimulated blood (LPS
      plasma), which is rich in monocyte-derived TF-bearing MPs. The median MP-TF
      activity was 1.06 pg/mL (range, from 0.19 to 10.34 pg/mL) in patients with
      pancreatic cancer, 0.61 pg/mL (range, from 0.36 to 0.79 pg/mL) in LPS-plasma, and
      0.18 pg/mL (range, from 0.04 to 0.39 pg/mL) in healthy individuals. MPs derived
      from LPS-plasma had the strongest impact on fibrin clot formation time (median,
      157.6 seconds; range, from 149.5 to 170.4 seconds). Fibrin clot formation
      occurred significantly later in MPs derived from patients with pancreatic cancer
      (median, 273.4 seconds; range, from 146.6 to 354.4 seconds; P < 0.001) and in
      healthy individuals (median, 299.0 seconds; range, from 261.1 to 417.9 seconds; P
      < 0.001). Only in MPs derived from LPS-plasma the fibrin clot formation time
      dependent strongly on TF (median prolongation after TF blockade: 68% in LPS
      plasma, 10% in patients with pancreatic cancer, and 4% in healthy individuals).
      In conclusion, highly elevated MP-TF activity was found in patients with
      metastatic pancreatic cancer, but TF-bearing MPs had a small effect on fibrin
      clot formation. TF-bearing MPs might not be the main mediators of the
      prothrombotic state associated with pancreatic cancer. However, the small but
      significant increase in coagulation potential by TF-bearing MPs might contribute
      to the multifactorial pathogenesis of venous thromboembolism in pancreatic
      cancer.

PMID- 23973168
TI  - Four-membered heterocycles-containing 4-anilino-quinazoline derivatives as
      epidermal growth factor receptor (EGFR) kinase inhibitors.
AB  - We report herein the design and synthesis of novel azaspirocycle or azetidine
      substituted 4-anilinoquinazoline derivatives. The EGFR inhibitory activities and
      in vitro antitumor potency of these newly synthesized compounds against two lung
      cancer cell lines HCC827 and A549 were evaluated. Most of the target compounds
      possess good inhibitory potency. In particular, compounds 21g with 2-oxa-6
      azaspiro[3.4]octane substituent was found to possess higher EGFR inhibitory
      activities and similar antitumor potency comparing to the lead compound gefitinib
      with improved water solubility. 

PMID- 23973169
TI  - Design, synthesis and biological evaluation of peptide derivatives of L-dopa as
      anti-parkinsonian agents.
AB  - A series of dipeptide derivatives of L-dopa were synthesized and investigated for
      their pharmacological activity using the unilaterally 6-hydroxydopamine (6-OHDA)
      lesioned rat as an experimental model of Parkinson's disease. Among them, (S)
      isopropyl 2-(2-amino-2-methylpropanamido)-3-(3,4-dihydroxyphenyl)propanoate (4 g)
      was found to be the most active compound, with 106% AUC activity and 149% peak
      activity of L-dopa after oral administration.

PMID- 23973170
TI  - Systems thinking, the Swiss Cheese Model and accident analysis: a comparative
      systemic analysis of the Grayrigg train derailment using the ATSB, AcciMap and
      STAMP models.
AB  - The Swiss Cheese Model (SCM) is the most popular accident causation model and is
      widely used throughout various industries. A debate exists in the research
      literature over whether the SCM remains a viable tool for accident analysis.
      Critics of the model suggest that it provides a sequential, oversimplified view
      of accidents. Conversely, proponents suggest that it embodies the concepts of
      systems theory, as per the contemporary systemic analysis techniques. The aim of
      this paper was to consider whether the SCM can provide a systems thinking
      approach and remain a viable option for accident analysis. To achieve this, the
      train derailment at Grayrigg was analysed with an SCM-based model (the ATSB
      accident investigation model) and two systemic accident analysis methods (AcciMap
      and STAMP). The analysis outputs and usage of the techniques were compared. The
      findings of the study showed that each model applied the systems thinking
      approach. However, the ATSB model and AcciMap graphically presented their
      findings in a more succinct manner, whereas STAMP more clearly embodied the
      concepts of systems theory. The study suggests that, whilst the selection of an
      analysis method is subject to trade-offs that practitioners and researchers must
      make, the SCM remains a viable model for accident analysis.

PMID- 23973171
TI  - Bringing policy relevance and scientific discipline to environmental risk
      assessment for genetically modified crops.
AB  - Although public opinion is important in deciding what is valued by society,
      governments have determined that scientific expertise is required to evaluate
      potential environmental effects of genetically modified (GM) crops. We suggest
      how to evaluate rigorously the environmental effects of GM crops in the context
      of a scientific investigation. Following a disciplined scientific approach to
      environmental risk assessment (ERA) for GM crops should help resolve controversy
      in identifying and addressing risk. 

PMID- 23973172
TI  - Parameter estimation and interval type-2 fuzzy sliding mode control of a z-axis
      MEMS gyroscope.
AB  - This paper reports a hybrid intelligent controller for application in single axis
      MEMS vibratory gyroscopes. First, unknown parameters of a micro gyroscope
      including unknown time varying angular velocity are estimated online via
      normalized continuous time least mean squares algorithm. Then, an additional
      interval type-2 fuzzy sliding mode control is incorporated in order to match the
      resonant frequencies and to compensate for undesired mechanical couplings. The
      main advantage of this control strategy is its robustness to parameters
      uncertainty, external disturbance and measurement noise. Consistent estimation of
      parameters is guaranteed and stability of the closed-loop system is proved via
      the Lyapunov stability theorem. Finally, numerical simulation is done in order to
      validate the effectiveness of the proposed method, both for a constant and time
      varying angular rate. 

PMID- 23973173
TI  - Mn(2+)-doped silica nanoparticles for hepatocyte-targeted detection of liver
      cancer in T1-weighted MRI.
AB  - With an aim to examine the possibility of developing a liver-specific MRI
      contrast agent that takes advantages of brightly enhanced MR images by Mn2+
      whilst making up the limitations of the pre-developed contrast agent, the Mn2+
      doped SiO2 nanoparticles (Mn-SiO2) were synthesized and their characteristics as
      MR contrast agents were investigated. The in vitro and in vivo investigations
      showed that Mn-SiO2 has unique MR contrast-enhancing characteristics that
      activate positive contrast enhancement in T1-weighted MR images only under low pH
      conditions by liberating Mn2+ ions from MR inactive nanoparticles. The
      administration of Mn-SiO2 to an orthotopic xenograft model of human
      hepatocellular carcinoma (HCC) resulted in a differentiation of enhancement
      periods between HCC and normal parenchyma tissues on T1-weighted MR images and
      consequently presented the duplicates of the highly contrast-enhanced liver image
      with an equal liver-to-HCC contrast ratio but opposite contrast. The Mn-SiO2
      enhanced MR imaging therefore allowed for the repetitive detection of the HCC
      within a single MR imaging session, which can help us to achieve more reliable
      diagnosis and characterization of liver lesions than is possible with any
      currently used Mn2+-based contrast agent. In addition, the in vivo
      biodistribution study also supported the effectiveness of Mn-SiO2 nanoparticles
      as a liver-specific MRI contrast agent, which efficiently delivers and releases
      the T1-contrasting Mn2+ ions to targeted hepatocytes.

PMID- 23973174
TI  - Paracrine exchanges of molecular signals between alginate-encapsulated pericytes
      and freely suspended endothelial cells within a 3D protein gel.
AB  - Paracrine signals, essential for the proper survival and functioning of tissues,
      may be mimicked by delivery of therapeutic proteins within engineered tissue
      constructs. Conventional delivery methods are of limited duration and are
      unresponsive to the local environment. We developed a system for sustained and
      regulated delivery of paracrine signals by encapsulating living cells of one type
      in alginate beads and co-suspending these cell-loaded particles along with
      unencapsulated cells of a second type within a 3D protein gel. This system was
      applied to vascular tissue engineering by placing human placental microvascular
      pericytes (PCs) in the particulate alginate phase and human umbilical vein
      endothelial cells (HUVECs) in the protein gel phase. Particle characteristics
      were optimized to keep the encapsulated PCs viable for at least two weeks.
      Encapsulated PCs were bioactive in vitro, secreting hepatocyte growth factor, an
      angiogenic protein, and responding to externally applied HUVEC-derived signals.
      Encapsulated PCs influenced HUVEC behavior in the surrounding gel by enhancing
      the formation of vessel-like structures when compared to empty alginate bead
      controls. In vivo, encapsulated PCs modulated the process of vascular self
      assembly by HUVECs in 3D gels following implantation into immunodeficient mice.
      We conclude that alginate encapsulated cells can provide functional paracrine
      signals within engineered tissues.

PMID- 23973175
TI  - Essential ("precursor") chemical control for heroin: impact of acetic anhydride
      regulation on US heroin availability.
AB  - BACKGROUND: To reduce heroin availability, the United Nations (UN) has encouraged
      nations to control acetic anhydride, an essential ("precursor") chemical
      typically necessary to the drug's production. This effort, a major environmental
      prevention policy, has received little evaluation. The United States, per the
      UN's lead, implemented acetic anhydride regulation in 11/1989. The present study
      examines whether the US regulation impacted US heroin availability. METHODS:
      Monthly series of three heroin availability indicators-heroin purity, heroin
      price, and amount of heroin seized-were constructed for the conterminous United
      States, the US Southwest (supplied predominantly with Mexican-produced heroin),
      and the US Northeast (supplied predominantly, at the time, with Southeast Asian
      produced heroin). Data came from the System to Retrieve Information from Drug
      Evidence (01/1987-04/2011). Impacts were assessed using ARIMA-intervention time
      series analysis. RESULTS: In each US area, heroin purity and amount seized rose
      and price decreased throughout the pre-intervention period. All of the indicators
      then reversed course at the time of the regulation. In the conterminous United
      States, the US Northeast, and the US Southwest, purity decreased (-40%, -25% and 
      50%, respectively); amount seized decreased (-27%, -37% and -39%, respectively);
      and price rose (+93%, +102% and +296%, respectively). Impacts lasted 2-5 years.
      CONCLUSION: US heroin availability decreased in association with the US acetic
      anhydride regulation. The impacts in the US Southwest and US Northeast suggest
      that heroin production in Mexico and Southeast Asia, respectively, was
      constrained. This study lends support to the contention that essential
      ("precursor") chemical control can be used to help address heroin.

PMID- 23973176
TI  - Prostate cancer incidence in light of the spatial distribution of another
      screening-detectable cancer.
AB  - Bias in spatial analyses that overlook compositional and contextual factors of
      communities can be substantial. We first examined spatial patterns among 11,728
      prostate cancer cases across Connecticut, 1994-98. A spatial scan statistic
      (SatScanTM) identified two locations where average annual incidence rates
      significantly exceeded the statewide level and two locations with significantly
      lower disease rates. Extending the analysis to adjust rates for age and
      race/ethnicity greatly minimized, but did not eliminate, geographic variation.
      Adjustment for age and poverty level of communities eliminated significant
      variability across locales. Similarly, analysis adjusted for age and covariation
      of colorectal cancer incidence rates across the state accounted for all
      significant variation previously observed. These results suggest that accounting
      for a "detection effect" due to clinical patterns of another screenable condition
      may be as useful as adjusting spatial data for variability of socio-economic
      conditions. 

PMID- 23973177
TI  - Random property allocation: A novel geographic imputation procedure based on a
      complete geocoded address file.
AB  - Allocating an incomplete address to randomly selected property coordinates within
      a locality, known as random property allocation, has many advantages over other
      geoimputation techniques. We compared the performance of random property
      allocation to four other methods under various conditions using a simulation
      approach. All methods performed well for large spatial units, but random property
      allocation was the least prone to bias and error under volatile scenarios with
      small units and low prevalence. Both its coordinate based approach as well as the
      random process of assignment contribute to its increased accuracy and reduced
      bias in many scenarios. Hence it is preferable to fixed or areal geoimputation
      for many epidemiological and surveillance applications. 

PMID- 23973178
TI  - Multivariate Bayesian spatial model of preterm birth and cardiovascular disease
      among Georgia women: Evidence for life course social determinants of health.
AB  - BACKGROUND: There is epidemiologic evidence that women who experience preterm
      birth (PTB) are at elevated risk for cardiovascular disease (CVD) later in life.
      Each outcome independently has noted spatial and socioeconomic gradients; we test
      for spatial structure in the population correlation of the two. METHODS:
      Exploratory spatial data analysis and multivariate Bayesian spatial models were
      fit to describe the spatial correlation of PTB with CVD among women in Georgia
      counties from 2002 to 2006. RESULTS: Global Moran's I and local-indicators of
      spatial association statistics suggest significant co-occurrence of CVD and PTB.
      Bayesian posterior estimates for multivariate correlation of these outcomes range
      from r=0.11-0.34 for CVD and PTB. Significant spatial correlation persists with
      control for county covariates among whites but not blacks. CONCLUSION: Modest
      evidence for spatial structure of the ecologic correlation of PTB and women's CVD
      is consistent with a lifecourse perspective on socially clustered determinants of
      health.

PMID- 23973179
TI  - Spatio-temporal clustering of the incidence of schizophrenia in Quebec, Canada
      from 2004 to 2007.
AB  - Exploring spatio-temporal patterns of disease incidence can help to identify
      areas of significantly elevated or decreased risk, providing potential etiologic
      clues. In this study, we present a spatio-temporal analysis of the incidence of
      schizophrenia in Quebec from 2004 to 2007 using administrative databases from the
      Regie de l'Assurance Maladie du Quebec and the hospital discharge database. We
      conducted purely spatial analyses for each age group adjusted by sex for the
      whole period using SatScan (version 9.1.1). Findings from the study indicated
      variations in the spatial clustering of schizophrenia according to sex and age.
      In term of incidence rate, there are high differences between urban and rural
      remote areas, as well as between the two main metropolitan areas of the province
      of Quebec (Island of Montreal and Quebec-City). 

PMID- 23973180
TI  - Immigrant maternal depression and social networks. A multilevel Bayesian spatial
      logistic regression in South Western Sydney, Australia.
AB  - The purpose is to explore the multilevel spatial distribution of depressive
      symptoms among migrant mothers in South Western Sydney and to identify any group
      level associations that could inform subsequent theory building and local public
      health interventions. Migrant mothers (n=7256) delivering in 2002 and 2003 were
      assessed at 2-3 weeks after delivery for risk factors for depressive symptoms.
      The binary outcome variables were Edinburgh Postnatal Depression Scale scores
      (EPDS) of >9 and >12. Individual level variables included were: financial income,
      self-reported maternal health, social support network, emotional support,
      practical support, baby trouble sleeping, baby demanding and baby not content.
      The group level variable reported here is aggregated social support networks. We
      used Bayesian hierarchical multilevel spatial modelling with conditional
      autoregression. Migrant mothers were at higher risk of having depressive symptoms
      if they lived in a community with predominantly Australian-born mothers and
      strong social capital as measured by aggregated social networks. These findings
      suggest that migrant mothers are socially isolated and current home visiting
      services should be strengthened for migrant mothers living in communities where
      they may have poor social networks.

PMID- 23973181
TI  - Spatial approximations of network-based individual level infectious disease
      models.
AB  - Often, when modeling infectious disease spread, the complex network through which
      the disease propagates is approximated by simplified spatial information. Here,
      we simulate epidemic spread through various contact networks and fit spatial
      based models in a Bayesian framework using Markov chain Monte Carlo methods.
      These spatial models are individual-level models which account for the spatio
      temporal dynamics of infectious disease. The focus here is on choosing a spatial
      model which best predicts the true probabilities of infection, as well as
      determining under which conditions such spatial models fail. Spatial models tend
      to predict infection probability reasonably well when disease spread is
      propagated through contact networks in which contacts are only within a certain
      distance of each other. If contacts exist over long distances, the spatial models
      tend to perform worse when compared to the network model. 

PMID- 23973182
TI  - An additive regression model for investigating the relationship between childhood
      health and socio-economic status.
AB  - Health risks associated with socio-economic status (SES) have extensively been
      studied in epidemiology. It is not uncommon that data used exhibit spatial
      correlation, nonlinear effects, overdispersion and heterogeneity, and structured
      additive regression (STAR) models permit incorporating these features in a single
      analytical framework. Nevertheless, most STAR models assume constant spatial
      effects. However, due to social or disease transmission processes, covariates may
      be space-varying. We explore this feature by fitting a multinomial logistic model
      on a joint response variable constructed from four health indicators (i.e. a
      child having fever, diarrhoea, or being stunted and underweight) and examine its
      relationship with SES estimated as a space-varying coefficient (SVC) variable.
      Implementation of the model follow a Bayesian framework. Our comparison with
      models that assume constant spatial effects shows superiority of the SVC model as
      well as confirms the fact that SES varies in space. 

PMID- 23973183
TI  - Comparability of Z-score equations of cardiac structures in hypoplastic left
      heart complex.
AB  - BACKGROUND: Hypoplastic left heart complex (HLHC) is characterized by a mitral
      valve or an aortic valve annular Z score < -2, antegrade flow in the ascending
      aorta, ductal dependency, coarctation or aortic arch hypoplasia, and absence of
      significant (sub)valvar stenosis. The Z scores of the mitral and aortic valve
      annuli are major determinants of HLHC. Therefore, the algorithm for Z-score
      calculation is essential for diagnosis. However, no single universal method of
      calculation is in use. In the scientific literature addressing HLHC, various Z
      score calculation methods have been applied. The aim of this study was to
      evaluate Z scores derived from two-dimensional echocardiographic dimensions in
      patients with HLHC. METHODS: To compare the different published methods using two
      dimensional echocardiographic measures for Z-score calculation, a cohort of 18
      newborns diagnosed with HLHC was retrospectively evaluated. In addition, the
      methods to determine body surface area in newborns were evaluated. RESULTS: Three
      Z-score calculation methods were included and compared. Using the method of
      Daubeney et al. to calculate Z scores in our cohort illustrated a lack of
      correlation beyond a Z score < 0, compared with the methods of Zilberman et al.
      and Pettersen et al. Z scores calculated using Zilberman et al.'s and Pettersen
      et al.'s methods were fairly consistent. The equations used by Pettersen et al.
      are based on the largest population of neonates. CONCLUSION: Although the
      different methods for calculating Z scores for mitral and aortic valve dimensions
      correspond fairly well in the normal range, Z scores < -2 diverge substantially.
      A useful scientific comparison of published data and outcomes of patients with
      HLHC remains elusive. The Z-score calculation algorithms used by Pettersen et al.
      appear to be the most appropriate for use in an evaluation of HLHC. Because these
      different methods can yield different values, reporting the method as well as the
      Z score is essential for an accurate diagnosis. Similarly, the method used to
      determine body surface area should be reported.

PMID- 23973184
TI  - Mislocalization of tactile stimuli applied to the trunk in spatial neglect.
AB  - INTRODUCTION: In patients with spatial neglect, body perception and
      representation are impaired - especially the projection of the anterior body
      midline in anterior space (the subjective "straight ahead"). However, data on
      more lateral body parts and the posterior body surface are scarce. We explored
      deviations of the perception of different body points located to the left or
      right of the midline and on the anterior and posterior body surfaces, and their
      lesion correlates in right hemisphere stroke patients. METHODS: Nine patients
      with neglect (diagnosed with paper and pencil and behavioural tests) were
      compared with six non-neglect patients and 13 healthy controls. The subjects had
      to use a mannequin to designate the body location that had been stimulated by a
      blunt pencil tip. Four horizontally arranged series of locations were traced on
      the anterior and posterior body surfaces at shoulder and navel levels. Each
      horizontal series comprised five equidistant test points, from left to right and
      corresponded to eleven labelled points on the mannequin. Patient errors were
      confronted to their anatomic lesions (MRI). RESULTS: We found a significant (p <=
      .05) rightward deviation of the left-side points and midpoint and a significant
      leftward deviation of the right-most point in neglect patients. Non-neglect
      patients and control subjects designated all the test points accurately. The body
      side (anterior or posterior) and the line (shoulder or navel) did not influence
      performance. Controls showed a definite reduction in variability for the midline
      points, which disappeared in neglect patients who showed a severe global increase
      of this variability. Errors depended on lesions centred on the intraparietal
      sulcus. CONCLUSIONS: These observations were compatible with a complex bias in
      body perception-representation extending to various lateral body points, with a
      left to right gradient. The right parietal cortex likely participates in
      processing such information.

PMID- 23973185
TI  - Neural encoding of movement sequences in the human brain.
AB  - Humans learn and remember thousands of motor skills, but how these skills are
      represented in the brain is not well understood. A recent study by Wiestler and
      Diedrichsen demonstrates for the first time that individual motor sequences can
      be identified based on the pattern of neural activity in a distributed network of
      motor cortical regions. 

PMID- 23973187
TI  - Resident-reported brachytherapy experience in ACGME-accredited radiation oncology
      training programs.
AB  - PURPOSE: To describe resident-reported experience in brachytherapy in
      Accreditation Council of Graduate Medical Education-accredited radiation oncology
      training programs over the last 5 years. METHODS AND MATERIALS: Archived reports
      of Accreditation Council of Graduate Medical Education final resident case logs
      from the last 5 years were reviewed and summarized. Brachytherapy was categorized
      according to the dose rate (low dose rate vs. high dose rate), technique
      (interstitial vs. intracavitary), and primary tumor site. Linear regression was
      used to test for trends. RESULTS: The mean number of total brachytherapy
      procedures performed per resident in the last 5 years has decreased from 80.8 in
      2006-2007 to 71.0 in 2010-2011, but the trend is not statistically significant.
      The average number of intracavitary procedures has remained steady. The average
      resident experience with interstitial brachytherapy has decreased in a
      statistically significant manner. The average number of interstitial procedures
      has decreased by 25%. CONCLUSIONS: The average number of interstitial procedures
      reported by residents has decreased by 25%. The community charged with training
      residents in interstitial brachytherapy should consider methods to ensure that
      residents obtain sufficient experience in the future.

PMID- 23973188
TI  - Grow your own: Protalix BioTherapeutics produces drugs in carrot cells.

PMID- 23973186
TI  - Effect of abiraterone acetate treatment on the quality of life of patients with
      metastatic castration-resistant prostate cancer after failure of docetaxel
      chemotherapy.
AB  - BACKGROUND: In a recent randomised, double-blind, phase III clinical trial among
      1195 patients with metastatic castration-resistant prostate cancer (mCRPC) who
      had failed docetaxel chemotherapy, abiraterone acetate was shown to significantly
      prolong overall survival compared with prednisone alone. Here we report on the
      impact of abiraterone therapy on the health-related quality of life (HRQoL)
      observed during this trial, assessed using the validated Functional Assessment of
      Cancer Therapy-Prostate (FACT-P) questionnaire. METHODS: All analyses were
      conducted using prespecified criteria for clinically meaningful improvement and
      deterioration in FACT-P total score as well as subscale scores; all respective
      thresholds were defined using an accepted methodology. Improvement was assessed
      only in patients with clinically significant functional status impairment at
      baseline. RESULTS: Significant improvements in the FACT-P total score were
      observed in 48% of patients receiving abiraterone versus 32% of patients
      receiving prednisone (p < 0.0001). Also, the median time to deterioration in FACT
      P total score was longer (p < 0.0001) in patients receiving abiraterone (59.9
      weeks versus 36.1 weeks). Similar differences were observed in all FACT-P
      subscales, with the exception of the social/family well-being domain. Median time
      to improvement in the physical well-being domain and the trial outcome index was
      significantly shorter (p < 0.01) with abiraterone when compared with the
      prednisone arm. CONCLUSIONS: The previously demonstrated survival benefit for
      abiraterone is accompanied by improvements in patient-reported HRQoL and a
      significant delay in HRQoL deterioration when compared with prednisone.

PMID- 23973189
TI  - Tuberculosis: feeding the enemy.
AB  - The nutrition of intracellular Mycobacterium tuberculosis is particularly
      experimentally intractable. In this issue of Chemistry and Biology, using 13C
      labeling with a new method of data analysis, Beste and colleagues provide direct
      evidence for the nutrients and pathways used by this ancient enemy of humanity.

PMID- 23973190
TI  - Synaptic MAGUK multimer formation is mediated by PDZ domains and promoted by
      ligand binding.
AB  - To examine the scaffolding properties of PSD-95, we have taken advantage of
      established ligand/PDZ domain interactions and developed a cell-based assay for
      investigating protein complex formation. This assay enables quantitative analysis
      of PDZ domain-mediated protein clustering using bimolecular fluorescence
      complementation (BiFC). Two nonfluorescent halves of EYFP were fused to C
      terminal PDZ ligand sequences to generate probes that sense for PDZ domain
      binding grooves of adjacent (interacting) molecules. When these probes are
      brought into proximity by the PDZ domains of a multiprotein scaffold, a
      functional fluorescent EYFP molecule can be detected. We have used this system to
      examine the properties of selected PSD-95 variants and thereby delineated regions
      of importance for PSD-95 complex formation. Further analysis led to the finding
      that PSD-95 multimerization is PDZ domain-mediated and promoted by ligand
      binding. 

PMID- 23973191
TI  - Evaluation of antioxidant and mutagenic activities of honey-sweetened cashew
      apple nectar.
AB  - In vitro chemical properties and antioxidant potential and in vivo mutagenic
      activity of honey-sweetened cashew apple nectar (HSCAN), a beverage produced from
      the cashew pseudo-fruit (Anacardium occidentale L.) and of its constituents were
      assessed. Analytical procedures were carried out to investigate the honey used in
      the HSCAN preparation, and the results observed are in accordance with Brazilian
      legal regulations, except for diastase number. HSCAN and pulp were investigated
      for ascorbic acid, carotenoid, anthocyanin and total phenolic contents, and both
      showed high acid ascorbic concentrations. Antioxidant capacity using 2,2-diphenyl
      1-picrylhydrazyl radical (DPPH) and/or beta-carotene/linoleic acid systems were
      applied and demonstrated a weak antioxidant capacity of honey and HSCAN, but
      cashew apple pulp demonstrated high antioxidant capacity. A weakly positive
      mutagenic effect of cashew pulp 20% was observed using the somatic mutation and
      recombination test (SMART) in Drosophila melanogaster only in the high
      bioactivation (HB) cross. On the contrary, HSCAN was not mutagenic in both
      standard and high bioactivation crosses. HSCAN exhibited slight antioxidant
      activity, which could be associated with the high amount of ascorbic acid found
      in the samples evaluated. The beverage prepared did not induce DNA damage in
      somatic cells of D. melanogaster, which means that it is neither mutagenic nor
      recombinagenic in this test system. 

PMID- 23973193
TI  - Ultrasonic sensor based defect detection and characterisation of ceramics.
AB  - Ceramic tiles, used in body armour systems, are currently inspected visually
      offline using an X-ray technique that is both time consuming and very expensive.
      The aim of this research is to develop a methodology to detect, locate and
      classify various manufacturing defects in Reaction Sintered Silicon Carbide
      (RSSC) ceramic tiles, using an ultrasonic sensing technique. Defects such as free
      silicon, un-sintered silicon carbide material and conventional porosity are often
      difficult to detect using conventional X-radiography. An alternative inspection
      system was developed to detect defects in ceramic components using an Artificial
      Neural Network (ANN) based signal processing technique. The inspection
      methodology proposed focuses on pre-processing of signals, de-noising, wavelet
      decomposition, feature extraction and post-processing of the signals for
      classification purposes. This research contributes to developing an on-line
      inspection system that would be far more cost effective than present methods and,
      moreover, assist manufacturers in checking the location of high density areas,
      defects and enable real time quality control, including the implementation of
      accept/reject criteria. 

PMID- 23973192
TI  - Preparative isolation of sargachromanol E from Sargassum siliquastrum by
      centrifugal partition chromatography and its anti-inflammatory activity.
AB  - Centrifugal partition chromatography (CPC) can be used to isolate various
      bioactive compounds from natural materials by one-step. We confirmed
      antioxidative compounds existed in chloroform (CHCl3) fraction of Sargassum
      siliquastrum using online-HPLC. Fractions (A, B, C, D and E) were separated from
      the CHCl3 fraction by preparative CPC (n-hexane:ethyl acetate:methanol:water,
      5:5:7:3, v/v). In this study, we proved that the isolated compounds exhibit anti
      inflammatory activities using lipopolysaccharide (LPS) stimulated RAW 264.7
      macrophages. The fraction A which exhibited the strongest inhibitory effect on
      nitric oxide (NO) production level, was confirmed as sargachromanol E by LC-MS
      ESI, (1)H NMR and (13)C NMR data. The sargachromanol E significantly reduced the
      inflammatory response in LPS induced macrophages, decreasing LPS-induced
      transcription factor of pro-inflammatory cyclooxygenase-2, NO synthase, phosphate
      P38, phosphate ERK1/2, LPS-stimulated tumor-necrosis factor alpha, interleukin-1
      beta and prostaglandin E2 release. In conclusion, it was suggested that
      sargachromanol E inhibited inflammation in LPS induced RAW 264.7 cells via MAPK
      pathway. 

PMID- 23973194
TI  - Evaluation of a diospyrin derivative as antileishmanial agent and potential
      modulator of ornithine decarboxylase of Leishmania donovani.
AB  - World health organization has called for academic research and development of new
      chemotherapeutic strategies to overcome the emerging resistance and side effects
      exhibited by the drugs currently used against leishmaniasis. Diospyrin, a bis
      naphthoquinone isolated from Diospyros montana Roxb., and its semi-synthetic
      derivatives, were reported for inhibitory activity against protozoan parasites
      including Leishmania. Presently, we have investigated the antileishmanial effect
      of a di-epoxide derivative of diospyrin (D17), both in vitro and in vivo.
      Further, the safety profile of D17 was established by testing its toxicity
      against normal macrophage cells (IC50~20.7 MUM), and also against normal BALB/c
      mice in vivo. The compound showed enhanced activity (IC50~7.2 MUM) as compared to
      diospyrin (IC50~12.6 MUM) against Leishmania donovani promastigotes. Again, D17
      was tested on L. donovani BHU1216 isolated from a sodium stibogluconate
      unresponsive patient, and exhibited selective inhibition of the intracellular
      amastigotes (IC50~0.18 MUM). Also, treatment of infected BALB/c mice with D17 at
      2mg/kg/day reduced the hepatic parasite load by about 38%. Subsequently,
      computational docking studies were undertaken on selected enzymes of
      trypanothione metabolism, viz. trypanothione reductase (TryR) and ornithine
      decarboxylase (ODC), followed by the enzyme kinetics, where D17 demonstrated non
      competitive inhibition of the L. donovani ODC, but could not inhibit TryR.

PMID- 23973195
TI  - Effect of nitaxozanide and pyrimethamine on astrocytes infected by Toxoplasma
      gondii in vitro.
AB  - BACKGROUND AND AIMS: T. gondii is a causal agent of encephalitis in
      immunocompromised patients. Pyrimethamine (PYR) has been the treatment of choice
      for toxoplasmosis. The aim of this study was to analyze the effect of
      nitazoxanide and pyrimethamine on astrocytes infected with T. gondii in vitro.
      METHODS: Rat astrocytes were cultured and infected with T. gondii. The effect of
      nitazoxanide (10, 20 and 30 MUg/mL) and pyrimethamine (7, 10 and 13 MUg/mL) on
      astrocytes infected was evaluated at 24 and 48 h post-infection. Tachyzoites and
      astrocytes were detected by the immunocytochemical method. T. gondii viability in
      astrocytes infected and treated with NTZ and PYR as well as NTZ and PYR
      cytotoxicity on astrocytes in vitro were evaluated by the MTT assay. RESULTS: The
      number of parasites in astrocytes treated with the drugs was significantly
      reduced when compared to control (p <0.001) at 24 and 48 h. Nitazoxanide produced
      97% T. gondii death in a concentration of 10 MUg/mL in 48 h infected astrocytes.
      At 48 h, the death rate of T. gondii was higher when treated with nitazoxanide
      than with pyrimethamine. A higher toxicity rate in astrocyte was observed when
      using pyrimethamine at 40 MUg/mL. CONCLUSIONS: Nitazoxanide reduced T. gondii
      infection more efficiently than pyrimethamine and is not cytotoxic to astrocytes
      at the administered dose.

PMID- 23973196
TI  - Physician-assisted death. Opinions of Mexican medical students and residents.
AB  - BACKGROUND AND AIMS: To explore opinions of young residents and medical students
      on physician-assisted death (PAD). METHODS: A questionnaire was answered by 140
      residents at the beginning of their residency and 99 third- or fourth-year
      medical students (46 attended religiously administered medical schools [RAMS] and
      53 lay-administered medical schools [LAMS]). Main questions were agreement with
      PAD, therapy withdrawal (TW) and personalized PAD (PPAD) on whether participants
      themselves would seek help to die. RESULTS: There were no differences of
      acceptance between residents and students but LAMS students had significantly
      higher agreement than RAMS students for PAD (68 vs. 33%), TW (79 vs. 39%) and
      PPAD (57 vs. 48%). LAMS students were also more willing to agree to a physician
      prescribe/inject a lethal drug, even if PAD were not legalized. However, legality
      was also an important issue, i.e., 25-58% of those unsure or opposed to PAD would
      reverse the decision if PAD were legalized, and 42-54% of those unwilling to TW
      would also reverse if written consent of the patient existed. Overall acceptance
      of residents and students was significantly higher than our previous study in
      nearly 1,000 older physicians (50 vs. 39% for PAD and 58 vs. 48% for TW).
      CONCLUSIONS: PAD and TW acceptability seems to be increasing in Mexico, probably
      as a result of evolving social attitudes that appeared to be counteracted by a
      more conservative upbringing at home in our young RAMS students.

PMID- 23973198
TI  - Forensic medicine: a forgotten world of opportunities and challenges for
      research.
AB  - Forensic medicine deals with a wide variety of cases. To accomplish the main
      objectives, this professional field needs to adopt and apply findings from other
      sciences, namely, different medical specialties and other forensic sciences. The
      opposite is not yet entirely true due to the fact that forensic medicine deals
      with cases that are very far away from other medical and scientific interests. It
      is obvious that this forgotten world of forensic medicine ... is also a new world
      of opportunities and challenges to research in all scientific areas. 

PMID- 23973197
TI  - Short-term glucose metabolism and gut hormone modulations after Billroth II
      gastrojejunostomy in nonobese gastric cancer patients with type 2 diabetes
      mellitus, impaired glucose tolerance and normal glucose tolerance.
AB  - BACKGROUND AND AIMS: Roux-en-Y gastric bypass (RYGB) is effective in controlling
      blood glucose in obese patients with type 2 diabetes (T2DM). The alterations of
      gut hormones involving in glucose metabolism may play an important role. Our aim
      was to explore the short-term effects of Billroth II gastrojejunostomy (a similar
      type of RYGB) on glucose metabolism and gut hormone modulations in nonobese
      patients with different levels of blood glucose tolerance. METHODS: Twenty one
      nonobese gastric cancer patients with different levels of blood glucose tolerance
      were submitted to Billroth II gastrojejunostomy. Among them, seven had T2DM,
      seven with impaired glucose tolerance (IGT) and the other seven had normal
      glucose tolerance (NGT). Body weight, glucose parameters, responses of plasma
      glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and gastric inhibitory
      polypeptide (GIP) to 75 g glucose were measured at baseline and 3 months after
      surgery. RESULTS: Similar weight losses were observed in all groups. Blood
      glucose was reduced in T2DM and IGT patients. Fasting and 30-min plasma glucose
      were increased significantly in NGT. GLP-1 showed insignificant alterations in
      all groups. PYY was evaluated in T2DM and IGT but remained unchanged in the NGT
      group. Decreased fasting and AUC GIP were observed in patients with T2DM;
      however, fasting and 30-min GIP were increased in NGT patients. CONCLUSIONS:
      Billroth II gastrojejunostomy is effective in reducing blood glucose in nonobese
      patients with T2DM and IGT but could deteriorate early blood glucose in nonobese
      NGT in a 3-month time period. Variations of glucose and gut hormone changes in
      the three groups suggest a role of proximal intestine in the pathophysiology of
      T2DM.

PMID- 23973199
TI  - A generally applicable cryopreservation method for nitrite-oxidizing bacteria.
AB  - Nitrite-oxidizing bacteria are key members of the global nitrogen cycle but their
      study is hampered by their limited availability in culture, mostly due to
      laborious cultivation procedures and the lack of stable preservation methods. In
      this study, it was demonstrated that long-term cryopreservation of nitrite
      oxidizing bacteria assigned to the genera Nitrobacter, Nitrospina, Nitrococcus,
      Nitrotoga and Nitrospira was possible using a simple and rapid protocol. Their
      survival was tested with different cryoprotecting agents, DMSO and Hatefi, and in
      various carbon-rich preservation media, ten-fold diluted TSB, and ten-fold
      diluted TSB supplemented with 1% trehalose, and 1% sucrose. Optimal preservation
      conditions were strain-dependent and marine strains appeared to be more sensitive
      to freezing than non-marine strains. Nevertheless, a general cryopreservation
      protocol using 10% dimethyl sulfoxide with or without ten-fold diluted trypticase
      soy broth as a preservation medium allowed successful preservation of all tested
      strains. 

PMID- 23973200
TI  - Aronia melanocarpa juice, a rich source of polyphenols, induces endothelium
      dependent relaxations in porcine coronary arteries via the redox-sensitive
      activation of endothelial nitric oxide synthase.
AB  - This study examined the ability of Aronia melanocarpa (chokeberry) juice, a rich
      source of polyphenols, to cause NO-mediated endothelium-dependent relaxations of
      isolated coronary arteries and, if so, to determine the underlying mechanism and
      the active polyphenols. A. melanocarpa juice caused potent endothelium-dependent
      relaxations in porcine coronary artery rings. Relaxations to A. melanocarpa juice
      were minimally affected by inhibition of the formation of vasoactive prostanoids
      and endothelium-derived hyperpolarizing factor-mediated responses, and markedly
      reduced by N(omega)-nitro-l-arginine (endothelial NO synthase (eNOS) inhibitor),
      membrane permeant analogs of superoxide dismutase and catalase, PP2 (Src kinase
      inhibitor), and wortmannin (PI3-kinase inhibitor). In cultured endothelial cells,
      A. melanocarpa juice increased the formation of NO as assessed by electron
      paramagnetic resonance spectroscopy using the spin trap
      iron(II)diethyldithiocarbamate, and reactive oxygen species using
      dihydroethidium. These responses were associated with the redox-sensitive
      phosphorylation of Src, Akt and eNOS. A. melanocarpa juice-derived fractions
      containing conjugated cyanidins and chlorogenic acids induced the phosphorylation
      of Akt and eNOS. The present findings indicate that A. melanocarpa juice is a
      potent stimulator of the endothelial formation of NO in coronary arteries; this
      effect involves the phosphorylation of eNOS via the redox-sensitive activation of
      the Src/PI3-kinase/Akt pathway mostly by conjugated cyanidins and chlorogenic
      acids. 

PMID- 23973201
TI  - Polymorphisms in DNA repair and apoptosis-related genes and clinical outcomes of
      patients with non-small cell lung cancer treated with first-line paclitaxel
      cisplatin chemotherapy.
AB  - This study was conducted to analyze a comprehensive panel of single nucleotide
      polymorphisms (SNPs) in genes in DNA repair and apoptosis pathways and determine
      the relationship between polymorphisms and treatment outcomes of patients with
      non-small cell lung cancer (NSCLC) treated with first-line paclitaxel-cisplatin
      chemotherapy. Three hundred eighty two patients with NSCLC were enrolled. Seventy
      four SNPs in 48 genes (42 SNPs in 27 DNA repair pathway genes and 32 SNPs in 21
      apoptotic pathway genes) were genotyped and their associations with chemotherapy
      response and overall survival (OS) were analyzed. Among SNPs in DNA repair genes,
      BRCA1 rs799917 was significantly associated with both chemotherapy response and
      OS. XRCC1 rs25487 exhibited a significant association with chemotherapy response
      and ERCC2 rs1052555 with OS. Four SNPs in apoptotic genes (TNFRSF1B rs1061624,
      BCL2 rs2279115, BIRC5 rs9904341, and CASP8 rs3769818) were significantly
      associated with OS, but not with response to chemotherapy. When the six SNPs
      which were associated with OS in individual analysis were combined, OS decreased
      as the number of bad genotypes increased (P(trend) = 2 * 10(-6)). Patients with
      3, and 4-6 bad genotypes had significantly worse OS compared with those carrying
      0-2 bad genotypes (adjusted hazard ratio [aHR] = 1.54, 95% CI = 1.14-2.08, P =
      0.005; aHR = 2.10, 95% CI = 1.55-2.85, P = 2 * 10(-6), respectively). In
      conclusion, these findings suggest that the six SNPs identified, particularly
      their combined genotypes, could be used as biomarkers predicting chemotherapy
      response and survival of NSCLC patients treated with first-line paclitaxel
      cisplatin chemotherapy.

PMID- 23973202
TI  - Radical treatment of synchronous oligometastatic non-small cell lung carcinoma
      (NSCLC): patient outcomes and prognostic factors.
AB  - OBJECTIVES: Metastatic non-small cell lung carcinoma (NSCLC) generally carries a
      poor prognosis, and systemic therapy is the mainstay of treatment. However,
      extended survival has been reported in patients presenting with a limited number
      of metastases, termed oligometastatic disease. We retrospectively reviewed the
      outcomes of such patients treated at two centers. MATERIALS AND METHODS: From
      September 1999-July 2012, a total of 61 patients with 1-3 synchronous metastases,
      who were treated with radical intent to all sites of disease, were identified
      from records of two cancer centers. Treatment was considered radical if it
      involved surgical resection and/or delivery of radiation doses >=13 * 3 Gy.
      RESULTS: Besides the primary tumor, 50 patients had a solitary metastasis, 9 had
      two metastases, and 2 had three metastases. Locations of metastases included the
      brain (n = 36), bone (n = 11), adrenal (n = 4), contralateral lung (n = 4), extra
      thoracic lymph nodes (n = 4), skin (n = 2) and colon (n = 1). Only one patient
      had metastases in two different organs. Median follow-up was 26.1 months (m),
      median overall survival (OS) was 13.5m, median progression free survival (PFS)
      was 6.6m and median survival after first progression (SAFP) was 8.3m. The 1- and
      2-year OS were, 54% and 38%, respectively. Significant predictors of improved OS
      were: smaller radiotherapy planning target volume (PTV) (p = 0.004) and surgery
      for the primary lung tumor (p < 0.001). Factors associated with improved SAFP
      included surgery for the primary lung tumor, presence of brain metastases, and
      absence of bone metastases. No significant differences in outcomes were observed
      between the two centers. CONCLUSION: Radical treatment of selected NSCLC patients
      presenting with 1-3 synchronous metastases can result in favorable 2-year
      survivals. Favorable outcomes were associated with intra-thoracic disease status:
      patients with small radiotherapy treatment volumes or resected disease had the
      best OS. Future prospective clinical trials, ideally randomized, should evaluate
      radical treatment strategies in such patients.

PMID- 23973203
TI  - Cost effectiveness of first-line pemetrexed plus platinum compared with other
      regimens in the treatment of patients with nonsquamous non-small cell lung cancer
      in the US outpatient setting.
AB  - This retrospective observational study evaluated cost effectiveness of first-line
      treatment of advanced nonsquamous non-small cell lung cancer (NSCLC) with
      pemetrexed/platinum (Pem/Plat) relative to paclitaxel/carboplatin (Pac/Carbo) and
      paclitaxel/carboplatin/bevacizumab (Pac/Carbo/Bev). Patients initiating first
      line treatment from 2006 to 2009 were identified in electronic medical records of
      20 US oncology practices. Pem/Plat patients were matched 1:1 on important
      characteristics with Pac/Carbo and Pac/Carbo/Bev patients and followed for 1 year
      to assess progression, survival, and costs. Bootstrapping was used to calculate
      the probability of falling within quadrants of the incremental cost-effectiveness
      plane. Kaplan-Meier analysis and Cox proportional hazards regression modeling
      were also performed. Three hundred Pem/Plat patients (mean age, 67.6 years; male,
      56.0%; PS 0/1, 71.0%) were matched with 300 patients in the other cohorts. Median
      PFS was 134 days (Pem/Plat) versus 106 days (Pac/Carbo) (hazard ratio [HR]: 0.67,
      P < 0.001) and 126 days (Pac/Carbo/Bev) (HR: 0.68, P < 0.001). Median OS was 298
      days (Pem/Plat) versus 218 days (Pac/Carbo) (HR: 0.88, P = 0.08) and 271 days
      (Pac/Carbo/Bev) (HR: 0.93, P = 0.31). Pem/Plat therapy costs were higher versus
      Pac/Carbo ($21,841 higher PFS; $19,137 higher OS; P <= 0.05) and lower versus
      Pac/Carbo/Bev ($15,160 lower PFS; $19,946 lower OS; P <= 0.05). Pem/Plat had a
      greater probability of higher costs/higher effectiveness versus Pac/Carbo (PFS,
      90.1%; OS, 96.3%) and lower costs/higher effectiveness versus Pac/Carbo/Bev (PFS,
      69.5%; OS, 85.0%). Pem/Plat had higher cost and effectiveness than Pac/Carbo;
      depending on a payer's or society's willingness to pay, Pem/Plat may be
      considered cost effective compared with Pac/Carbo. Pem/Plat yielded greater
      effectiveness with lower costs than Pac/Carbo/Bev.

PMID- 23973204
TI  - The effect of dominance on polymorphism in Mullerian mimicry.
AB  - Dominance controls the phenotype of heterozygous individuals, and plays an
      important role in the maintenance of polymorphism. Here we focus on the dominance
      acting on warning-pattern polymorphism in species engaged in Mullerian mimicry.
      Mullerian mimics are toxic species which display bright colour patterns used as a
      warning signal to predators and are subject to local positive density-dependent
      selection. Some Mullerian mimics are polymorphic due to a selection/migration
      balance in spatially heterogeneous communities of prey. Since heterozygotes at a
      locus controlling warning pattern might exhibit intermediate, non-mimetic
      heterozygous morphs, dominance is likely to influence the polymorphism at this
      locus. Using a deterministic model describing migration, density-dependent
      predation and reproduction, we investigated the influence of dominance on the
      dynamics of alleles at locus determining mimetic phenotype. Our results suggest
      dominance may interact with migration and selection and plays an important role
      in shaping the conditions of polymorphism persistence and the frequency of
      alleles at this locus. Our results thus highlight the important role of dominance
      in the dynamics of polymorphism at loci under balancing selection due to
      environmental heterogeneity. 

PMID- 23973205
TI  - A novel framework for predicting the use of facultative heterothermy by
      endotherms.

PMID- 23973207
TI  - Individual and familial risk and protective correlates of physical and
      psychological peer victimization.
AB  - The purpose of this study was to explore the association between youth
      characteristics, parenting behavior, and family violence and risk of physical
      and/or psychological peer victimization using a sample of 856 adolescents aged 10
      17. Additionally, we examined whether the relation between parenting behaviors
      and victimization was moderated by age and gender. Data for this study were drawn
      from the first wave of the Developmental Victimization Survey. The results
      revealed unique associations between youth and familial correlates and odds for
      experiencing physical, psychological, and both types of victimization. Gender was
      found to be a statistically significant moderator of the relation between
      parental monitoring and odds of experiencing both physical and psychological peer
      victimization. Implications for bully prevention and intervention are discussed. 

PMID- 23973206
TI  - Predicting critical transitions in a model of systemic inflammation.
AB  - The human body can be viewed as a dynamical system, with physiological states
      such as health and disease broadly representing steady states. From this
      perspective, and given inter- and intra-individual heterogeneity, an important
      task is identifying the propensity to transition from one steady state to
      another, which in practice can occur abruptly. Detecting impending transitions
      between steady states is of significant importance in many fields, and thus a
      variety of methods have been developed for this purpose, but lack of data has
      limited applications in physiology. Here, we propose a model-based approach
      towards identifying critical transitions in systemic inflammation based on a
      minimal amount of assumptions about the availability of data and the structure of
      the system. We derived a warning signal metric to identify forthcoming abrupt
      transitions occurring in a mathematical model of systemic inflammation with a
      gradually increasing bacterial load. Intervention to remove the inflammatory
      stimulus was successful in restoring homeostasis if undertaken when the warning
      signal was elevated rather than waiting for the state variables of the system
      themselves to begin moving to a new steady state. The proposed combination of
      data and model-based analysis for predicting physiological transitions represents
      a step forward towards the quantitative study of complex biological systems. 

PMID- 23973208
TI  - The first stage of cardinal direction selectivity is localized to the dendrites
      of retinal ganglion cells.
AB  - Inferring the direction of image motion is a fundamental component of visual
      computation and essential for visually guided behavior. In the retina, the
      direction of image motion is computed in four cardinal directions, but it is not
      known at which circuit location along the flow of visual information the cardinal
      direction selectivity first appears. We recorded the concerted activity of the
      neuronal circuit elements of single direction-selective (DS) retinal ganglion
      cells at subcellular resolution by combining GCaMP3-functionalized transsynaptic
      viral tracing and two-photon imaging. While the visually evoked activity of the
      dendritic segments of the DS cells were direction selective, direction-selective
      activity was absent in the axon terminals of bipolar cells. Furthermore, the
      glutamate input to DS cells, recorded using a genetically encoded glutamate
      sensor, also lacked direction selectivity. Therefore, the first stage in which
      extraction of a cardinal motion direction occurs is the dendrites of DS cells. 

PMID- 23973210
TI  - Analysis of the relationship of insulin-like growth factor-1 to the growth
      velocity and feeding of healthy infants.
AB  - CONTEXT: Infancy is the fastest growth period in a child's development after
      birth, but little is known about hormonal regulation mechanism for the growth and
      development of this period. OBJECTIVE: The objective of this study is to analyze
      the trend of serum IGF-1 levels in healthy infants and the relationship of IGF-1
      to the growth velocity and feeding method of infants. DESIGN: Population-based
      birth cohort study. SETTING: The study was conducted in the Third Hospital of
      Peking University. PARTICIPANTS: Study participants were 484 healthy infants, all
      of whom were full-term and appropriate for gestational age (238 boys and 246
      girls). INTERVENTIONS: Interventions were anthropometrical measurements, feeding
      methods recorded every 1 to 2 months and serum samples (2, 4, 6, 8, 10,12
      months). MAIN OUTCOME MEASURES: Height, weight, feeding methods and serum IGF-1
      were the main outcome measures. RESULTS: Serum IGF-1 levels decreased in the
      following 2 months in boys but in females levels remained relatively high between
      2 to 3 months after birth and then started to decrease. It reached the lowest
      point at Months 7-8, and was on a slow rise in both male infants and female
      infants thereafter. Serum IGF-1 levels were significantly higher in female
      infants [112.65 ng/ml (CI 91.82, 133.89)] than in male infants [74.38 ng/ml (CI
      53.14, 95.61)] at early infancy. Infants fed with human milk had lower serum IGF
      1 levels than infants fed with formula milk or human milk plus formula milk
      (66.94 +/- 45.85 ng/ml, 72.56 +/- 36.55 ng/ml, 79.89 +/- 51.79 ng/ml,
      respectively; P = 0.019). IGF-1 levels were positively correlated to the growth
      velocity of body length (P<0.01). CONCLUSION: This study provides the trend for
      IGF-1 levels at infancy. It is highly possible that IGF-1 plays an important role
      in the regulation and control of length increases in infants, and feeding method
      influences serum IGF-1 levels.

PMID- 23973209
TI  - A presynaptic ENaC channel drives homeostatic plasticity.
AB  - An electrophysiology-based forward genetic screen has identified two genes,
      pickpocket11 (ppk11) and pickpocket16 (ppk16), as being necessary for the
      homeostatic modulation of presynaptic neurotransmitter release at the Drosophila
      neuromuscular junction (NMJ). Pickpocket genes encode Degenerin/Epithelial Sodium
      channel subunits (DEG/ENaC). We demonstrate that ppk11 and ppk16 are necessary in
      presynaptic motoneurons for both the acute induction and long-term maintenance of
      synaptic homeostasis. We show that ppk11 and ppk16 are cotranscribed as a single
      mRNA that is upregulated during homeostatic plasticity. Acute pharmacological
      inhibition of a PPK11- and PPK16-containing channel abolishes the expression of
      short- and long-term homeostatic plasticity without altering baseline presynaptic
      neurotransmitter release, indicating remarkable specificity for homeostatic
      plasticity rather than NMJ development. Finally, presynaptic calcium imaging
      experiments support a model in which a PPK11- and PPK16-containing DEG/ENaC
      channel modulates presynaptic membrane voltage and, thereby, controls calcium
      channel activity to homeostatically regulate neurotransmitter release.

PMID- 23973211
TI  - Fragment-based discovery of focal adhesion kinase inhibitors.
AB  - Chemically diverse fragment hits of focal adhesion kinase (FAK) were discovered
      by surface plasmon resonance (SPR) screening of our in-house fragment library.
      Site specific binding of the primary hits was confirmed in a competition setup
      using a high-affinity ATP-site inhibitor of FAK. Protein crystallography revealed
      the binding mode of 41 out of 48 selected fragment hits within the ATP-site.
      Structural comparison of the fragment binding modes with a DFG-out inhibitor of
      FAK initiated first synthetic follow-up optimization leading to improved binding
      affinity. 

PMID- 23973212
TI  - Rhodamine-propargylic esters for detection of mitochondrial hydrogen sulfide in
      living cells.
AB  - Flow cytometric detection of mitochondrial H2S was achieved with propargylic
      esters of rhodamine B which selectively react with H2S via cationic rhodamine
      moiety directed thiolysis of the propargylic esters to give nonfluorescent
      rhodamine thio-spirolactone. 

PMID- 23973214
TI  - The influence of soft contact lens wear and two weeks cessation of lens wear on
      corneal curvature.
AB  - INTRODUCTION: Accurate corneal measurements are crucial in corneal refractive
      surgery (CRS) to ensure successful outcomes. Soft contact lens (SCL) wear may
      result in changes to corneal curvature and structure. United States Food and Drug
      Administration (FDA) pre-operative guidelines recommend that prior to CRS, SCL
      wearers cease SCL wear for "at least two weeks before examination and treatment"
      [1]. Corneal curvature changes induced by SCL wear may take longer than two weeks
      to resolve. PURPOSE: To examine the effect of SCL wear on corneal curvature
      before and following two weeks SCL wear cessation. To explore the possible impact
      of different SCL materials and years of SCL wear. METHODS: Retrospective data
      analysis, between a group of SCL wearers (SCL: n=45); and a non-contact lens
      control group (NCL: n=45). Corneal curvature parameters were measured using the
      Pentacam (Oculus, Germany), before and following two weeks cessation of SCL wear.
      RESULTS: No significant differences in keratometry or Sagittal radius of
      curvature between SCL and NCL groups prior to or following SCL cessation.
      Tangential radius of curvature showed significant inferior steepening for the SCL
      group prior to SCL cessation (SCL vs. NCL; 7.77+/-0.30mm vs. 7.90+/-0.30mm;
      p=0.04). Following two weeks cessation of SCL wear this appeared to have
      resolved. CONCLUSIONS: Two weeks cessation of SCL wear appears sufficient for
      resolution of corneal curvature changes with modern SCL materials and years of
      SCL wear. However, further studies with longer lens deprivation periods are
      required to ensure stability for all SCL wearing patients.

PMID- 23973213
TI  - Doxorubicin-antioxidant co-drugs.
AB  - Doxorubicin-antioxidant multitarget compounds 6 and 7 were obtained by combining
      doxorubicin (DOX) with caffeic and ferulic acids through an ester linkage at C
      14. The products were studied in in vitro models of cardiomyocytes and breast
      cancer cells, characterized by different degrees of resistance to DOX, due to
      different expressions of ATP binding cassette (ABC) transporters. Compound 7 was
      found to be less toxic than DOX in cardiomyocytes and to display the same
      possibly higher toxicity against the resistant breast cancer cells. This result
      shows that appropriate DOX-antioxidant co-drugs can limit the onset of cardiac
      damage, a significant side-effect of DOX, without impairing the antitumor
      activity of the parent antibiotic. 

PMID- 23973215
TI  - 4C-ing the Igh Landscape.
AB  - The assembly of antigen receptors in developing B lymphocytes is determined by
      the spatio-temporal organization of the immunoglobulin heavy chain locus (Igh).
      In this issue of Immunity, Medvedovic et al. (2013) provide a comprehensive
      dynamic view of the Igh locus architecture. 

PMID- 23973216
TI  - A degrading view of regulatory T cells.
AB  - Studies by van Loosdregt et al. and Chen et al. in this issue of Immunity provide
      evidence for previously unrecognized players that regulate FOXP3 degradation.
      These are interesting developments that point to unappreciated mechanisms by
      which inflammatory signals can impact expression of FOXP3 and possibly the
      stability of Treg cell phenotypes. 

PMID- 23973217
TI  - Generating CD8 T cell heterogeneity: attack of the clones.
AB  - Pathogen-induced inflammation modulates CD8 T cell effector and memory
      differentiation. In this issue of Immunity, Plumlee et al. (2013) demonstrate
      that clonally distinct CD8 T cells have the ability to generate numerous types of
      effector cell fates based on extrinsic pathogen-induced environmental cues. 

PMID- 23973218
TI  - Keeping the peace: aryl hydrocarbon receptor signaling modulates the mucosal
      microbiota.
AB  - In this issue of Immunity, Zelante et al. (2013) and Qiu et al. (2013) provide
      mechanistic insights into functional interactions between commensal microbes and
      innate lymphoid cells via the aryl hydrocarbon receptor. 

PMID- 23973219
TI  - Testosterone: more than having the guts to win the Tour de France.
AB  - Sex bias in susceptibility to autoimmune diseases is evident but poorly
      characterized. Yurkovetskiy et al. (2013) report that host testosterone mediates
      changes in the microbiome to confer protection to adult male NOD mice from type 1
      diabetes. 

PMID- 23973220
TI  - Autophagy and cellular immune responses.
AB  - Autophagy constitutes a mechanism for the sequestration and lysosomal degradation
      of various cytoplasmic structures, including damaged organelles and invading
      microorganisms. Autophagy not only represents an essential cell-intrinsic
      mechanism to protect against internal and external stress conditions but also
      shapes cellular immunity. Recent evidence indicates that autophagic responses in
      antigen-donor cells affect the release of several cytokines and "danger signals."
      Thus, especially when it precedes cell death, autophagy alerts innate immune
      effectors to elicit cognate immune responses. Autophagy is also important for the
      differentiation, survival, and activation of myeloid and lymphoid cells.
      Accordingly, inherited mutations in autophagy-relevant genes are associated with
      immune diseases, whereas oncogenesis-associated autophagic defects promote the
      escape of developing tumors from immunosurveillance. Here, we discuss the
      regulation of autophagy in the course of cellular immune responses and emphasize
      its impact on the immunogenicity of antigen-donor cells and on the activity of
      antigen-presenting cells and T lymphocytes. 

PMID- 23973221
TI  - Flexible long-range loops in the VH gene region of the Igh locus facilitate the
      generation of a diverse antibody repertoire.
AB  - The immunoglobulin heavy-chain (Igh) locus undergoes large-scale contraction in
      pro-B cells, which facilitates VH-DJH recombination by juxtaposing distal VH
      genes next to the DJH-rearranged gene segment in the 3' proximal Igh domain. By
      using high-resolution mapping of long-range interactions, we demonstrate that
      local interaction domains established the three-dimensional structure of the
      extended Igh locus in lymphoid progenitors. In pro-B cells, these local domains
      engaged in long-range interactions across the Igh locus, which depend on the
      regulators Pax5, YY1, and CTCF. The large VH gene cluster underwent flexible long
      range interactions with the more rigidly structured proximal domain, which
      probably ensures similar participation of all VH genes in VH-DJH recombination to
      generate a diverse antibody repertoire. These long-range interactions appear to
      be an intrinsic feature of the VH gene cluster, because they are still generated
      upon mutation of the EMU enhancer, IGCR1 insulator, or 3' regulatory region in
      the proximal Igh domain. 

PMID- 23973222
TI  - Stabilization of the transcription factor Foxp3 by the deubiquitinase USP7
      increases Treg-cell-suppressive capacity.
AB  - Stable Foxp3 expression is required for the development of functional regulatory
      T (Treg) cells. Here, we demonstrate that the expression of the transcription
      factor Foxp3 can be regulated through the polyubiquitination of multiple lysine
      residues, resulting in proteasome-mediated degradation. Expression of the
      deubiquitinase (DUB) USP7 was found to be upregulated and active in Treg cells,
      being associated with Foxp3 in the nucleus. Ectopic expression of USP7 decreased
      Foxp3 polyubiquitination and increased Foxp3 expression. Conversely, either
      treatment with DUB inhibitor or USP7 knockdown decreased endogenous Foxp3 protein
      expression and decreased Treg-cell-mediated suppression in vitro. Furthermore, in
      a murine adoptive-transfer-induced colitis model, either inhibition of DUB
      activity or USP7 knockdown in Treg cells abrogated their ability to resolve
      inflammation in vivo. Our data reveal a molecular mechanism in which rapid
      temporal control of Foxp3 expression in Treg cells can be regulated by USP7,
      thereby modulating Treg cell numbers and function. 

PMID- 23973223
TI  - The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive
      activity by promoting degradation of the transcription factor Foxp3.
AB  - Regulatory T (Treg) cells suppress inflammatory immune responses and autoimmunity
      caused by self-reactive T cells. The key Treg cell transcription factor Foxp3 is
      downregulated during inflammation to allow for the acquisition of effector T cell
      like functions. Here, we demonstrate that stress signals elicited by
      proinflammatory cytokines and lipopolysaccharides lead to the degradation of
      Foxp3 through the action of the E3 ubiquitin ligase Stub1. Stub1 interacted with
      Foxp3 to promote its K48-linked polyubiquitination in an Hsp70-dependent manner.
      Knockdown of endogenous Stub1 or Hsp70 prevented Foxp3 degradation. Furthermore,
      the overexpression of Stub1 in Treg cells abrogated their ability to suppress
      inflammatory immune responses in vitro and in vivo and conferred a T-helper-1
      cell-like phenotype. Our results demonstrate the critical role of the stress
      activated Stub1-Hsp70 complex in promoting Treg cell inactivation, thus providing
      a potential therapeutic target for the intervention against autoimmune disease,
      infection, and cancer. 

PMID- 23973224
TI  - Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and
      balance mucosal reactivity via interleukin-22.
AB  - Endogenous tryptophan (Trp) metabolites have an important role in mammalian gut
      immune homeostasis, yet the potential contribution of Trp metabolites from
      resident microbiota has never been addressed experimentally. Here, we describe a
      metabolic pathway whereby Trp metabolites from the microbiota balance mucosal
      reactivity in mice. Switching from sugar to Trp as an energy source (e.g., under
      conditions of unrestricted Trp availability), highly adaptive lactobacilli are
      expanded and produce an aryl hydrocarbon receptor (AhR) ligand-indole-3-aldehyde
      that contributes to AhR-dependent Il22 transcription. The resulting IL-22
      dependent balanced mucosal response allows for survival of mixed microbial
      communities yet provides colonization resistance to the fungus Candida albicans
      and mucosal protection from inflammation. Thus, the microbiota-AhR axis might
      represent an important strategy pursued by coevolutive commensalism for fine
      tuning host mucosal reactivity contingent on Trp catabolism. 

PMID- 23973234
TI  - 50 Years ago in The Journal of Pediatrics: Children of mothers with
      phenylketonuria.

PMID- 23973233
TI  - Developing physician-scientists in the fields of neonatology and pediatric
      critical care medicine: an effort to formulate a departmental policy.

PMID- 23973225
TI  - Gender bias in autoimmunity is influenced by microbiota.
AB  - Gender bias and the role of sex hormones in autoimmune diseases are well
      established. In specific pathogen-free nonobese diabetic (NOD) mice, females have
      1.3-4.4 times higher incidence of type 1 diabetes (T1D). Germ-free (GF) mice lost
      the gender bias (female-to-male ratio 1.1-1.2). Gut microbiota differed in males
      and females, a trend reversed by male castration, confirming that androgens
      influence gut microbiota. Colonization of GF NOD mice with defined microbiota
      revealed that some, but not all, lineages overrepresented in male mice supported
      a gender bias in T1D. Although protection of males did not correlate with blood
      androgen concentration, hormone-supported expansion of selected microbial
      lineages may work as a positive-feedback mechanism contributing to the sexual
      dimorphism of autoimmune diseases. Gene-expression analysis suggested pathways
      involved in protection of males from T1D by microbiota. Our results favor a two
      signal model of gender bias, in which hormones and microbes together trigger
      protective pathways. 

PMID- 23973235
TI  - 50 Years ago in The Journal of Pediatrics: sudden and unexpected death in
      infants: II. Viral infections as causative factors.

PMID- 23973236
TI  - 50 Years ago in The Journal of Pediatrics: Bacteriuria in children with acute
      febrile illnesses.

PMID- 23973237
TI  - 50 Years ago in The Journal Of Pediatrics: Technique for peroral small intestinal
      biopsy in children.

PMID- 23973238
TI  - 50 Years ago in The Journal of Pediatrics: Treatment of juvenile thyrotoxicosis.

PMID- 23973239
TI  - Thin catheter surfactant administration during spontaneous breathing in very low
      birth weight infants is associated with reduced need for mechanical ventilation.

PMID- 23973240
TI  - Prenatal cocaine exposure is associated with variable, small effects on
      adolescent functioning.

PMID- 23973241
TI  - Childhood television viewing is associated with antisocial behavior in adulthood.

PMID- 23973242
TI  - Childhood migraine is associated with a history of infantile colic.

PMID- 23973243
TI  - Prenatal valproate exposure is associated with autism spectrum disorder and
      childhood autism.

PMID- 23973244
TI  - Postpartum prevention of pertussis in a French maternity hospital: impact on
      general practitioners.
AB  - A protocol which combined giving parents' information and issuing them with a
      pertussis vaccine prescription was introduced in 2008 in the maternity ward of
      the Angers University Hospital, France. As a result, a vaccine coverage rate of
      69% among mothers and 63% among fathers was achieved. The aim of this study was
      to assess the impact of this protocol on general practitioners in the county for
      which Angers is the main specialist maternity unit, in terms of their opinions on
      it and any changes they made to their practices. An anonymous, descriptive survey
      was carried out in 2009, via a questionnaire sent out to the 655 general
      practitioners (GPs). The response rate among the GPs was 77% (508/655). Of the
      respondents, 97.8% (497/508) were familiar with the vaccination recommendations
      and of these, 30.4% (150/495; missing data n=2) knew of them through the
      information letter given out by the maternity unit and 97.6% (482/494; missing
      data n=3) stated that they had informed their patients of them. Of the GPs who
      replied, 97.5% (476/488; missing data n=9) approved of the strategy, while 60.4%
      of them (285/472; missing data n=4) said they had changed their information
      practices since 2008 and 67.2% (307/457; missing data n=19) said they had changed
      their vaccination practices over the same period. Most of the GPs (53% (241/454);
      missing data n=43) approved of the maternity unit giving parents the vaccine. The
      pertussis prevention protocol introduced by the maternity unit was clearly
      understood by the general practitioners and led them to significantly change
      their information and vaccination practices. 

PMID- 23973245
TI  - Development status and future prospects for a vaccine against Chlamydia
      trachomatis infection.
AB  - Chlamydia trachomatis continues to be the most commonly reported sexually
      transmitted bacterial infection in many countries with more than 100 million new
      cases estimated annually. These acute infections translate into significant
      downstream health care costs, particularly for women, where complications can
      include pelvic inflammatory disease and other disease sequelae such as tubal
      factor infertility. Despite years of research, the immunological mechanisms
      responsible for protective immunity versus immunopathology are still not well
      understood, although it is widely accepted that T cell driven IFN-g and Th17
      responses are critical for clearing infection. While antibodies are able to
      neutralize infections in vitro, alone they are not protective, indicating that
      any successful vaccine will need to elicit both arms of the immune response. In
      recent years, there has been an expansion in the number and types of antigens
      that have been evaluated as vaccines, and combined with the new array of mucosal
      adjuvants, this aspect of chlamydial vaccinology is showing promise. Most
      recently, the opportunities to develop successful vaccines have been given a
      significant boost with the development of a genetic transformation system for
      Chlamydia, as well as the identification of the key role of the chlamydial
      plasmid in virulence. While still remaining a major challenge, the development of
      a successful C. trachomatis vaccine is starting to look more likely. 

PMID- 23973246
TI  - Lesser protein degradation machinery correlates with higher BM86 tick vaccine
      efficacy in Rhipicephalus annulatus when compared to Rhipicephalus microplus.
AB  - Infestations with cattle ticks, Rhipicephalus (Boophilus) microplus and
      Rhipicephalus annulatus, economically impact cattle production in tropical and
      subtropical regions of the world. Vaccines containing the recombinant R.
      microplus BM86 gut antigen were developed and commercialized to induce an
      immunological protection in cattle against tick infestations. These vaccines
      demonstrated that tick control by vaccination is cost-effective, reduces
      environmental contamination and prevents the selection of drug resistant ticks
      that result from repeated acaricide applications. The protection elicited by BM86
      containing vaccines against tick infestations is mediated by a collaborative
      action between the complement system and IgG antibodies. The efficacy of the
      vaccination with BM86 and other tick antigens is always higher for R. annulatus
      than against R. microplus, suggesting that tick genetic and/or physiological
      factors may affect tick vaccine efficacy. These factors may be related to BM86
      protein levels or tick physiological processes such as feeding and protein
      degradation that could result in more efficient antibody-antigen interactions and
      vaccine efficacy. To test this hypothesis, we compared the proteome in R.
      annulatus and R. microplus female ticks after feeding on BM86-vaccinated and
      control cattle. The results showed that cattle proteins were under represented in
      R. annulatus when compared to R. microplus, suggesting that R. annulatus ticks
      ingested less blood, a difference that increased when feeding on vaccinated
      cattle, probably reflecting the effect of antibody-BM86 interactions on this
      process. The results also showed that tick protein degradation machinery was
      under represented in R. annulatus when compared to R. microplus. BM86 mRNA and
      protein levels were similar in both tick species, suggesting that lesser protease
      activity in R. annulatus results in more efficient antibody-antigen interactions
      and higher vaccine efficacy. These results have important implications for tick
      vaccine research, indicating that not only genetic differences, but also
      physiological factors may influence tick vaccine efficacy.

PMID- 23973247
TI  - Generation and preclinical evaluation of a DENV-1/2 prM+E chimeric live
      attenuated vaccine candidate with enhanced prM cleavage.
AB  - In the absence of a vaccine or sustainable vector control measures, illnesses
      caused by dengue virus infection remain an important public health problem in
      many tropical countries. During the export of dengue virus particles, furin
      mediated cleavage of the prM envelope protein is usually incomplete, thus
      generating a mixture of immature, partially mature and mature extracellular
      particles. Variations in the arrangement and conformation of the envelope
      proteins among these particles may be associated with their different roles in
      shaping the antibody response. In an attempt to improve upon live, attenuated
      dengue vaccine approaches, a mutant chimeric virus, with enhanced prM cleavage,
      was generated by introducing a cleavage-enhancing substitution into a chimeric
      DENV-1/2 virus genome, encoding the prM+E sequence of a recent DENV-1 isolate
      under an attenuated DENV-2 genetic background. A modest increase in virus
      specific infectivity observed in the mutant chimeric virus affected neither the
      attenuation phenotype, when assessed in the suckling mouse neurovirulence model,
      nor multiplication in mosquitoes. The two chimeric viruses induced similar levels
      of anti-DENV-1 neutralizing antibody response in mice and rhesus macaques, but
      more efficient control of viremia during viral challenge was observed in macaques
      immunized with the mutant chimeric virus. These results indicate that the DENV
      1/2 chimeric virus, with enhanced prM cleavage, could be useful as an alternative
      live, attenuated vaccine candidate for further tests in humans. 

PMID- 23973248
TI  - Varicella zoster virus infection occurs at a relatively young age in The
      Netherlands.
AB  - INTRODUCTION: To date, there is no universal varicella vaccination in the
      Netherlands. We studied the seroprevalence of varicella zoster virus (VZV)
      specific antibodies and determinants for seropositivity among participants of a
      serosurveillance study, conducted in 2006/2007 among Dutch inhabitants 0-79 years
      of age. MATERIALS AND METHODS: Serological testing of 6386 blood samples for VZV
      was performed with a fluorescent bead-based multiplex immunoassay. Seroprevalence
      and geometric mean concentration (GMC) were weighted for age, sex, ethnicity, and
      urbanization rate to the total Dutch population. Determinants for VZV
      seropositivity were identified among children younger than 6 years of age using a
      logistic regression model. RESULTS: The overall seroprevalence of VZV specific
      antibodies in the Dutch population was 94.6% (95% CI: 93.2-96.0%). This
      seroprevalence increased rapidly with age: at 6 years of age, more than 95% were
      seropositive. Determinants associated with lower VZV seropositivity were: young
      age, first-generation non-Dutch ethnicity, and low frequency of attendance at a
      day care center or nursery school. The GMC increased with age and was lower for
      women than for men from the age of 20 years onwards. CONCLUSIONS: This study
      confirmed that VZV infection occurs at a younger age in the Netherlands compared
      to other countries, which might explain the low disease burden due to varicella.
      Introduction of universal varicella vaccination is not a foregone conclusion in
      the Netherlands. Changes in migration and day care usage will influence the age
      specific risk on varicella and should therefore be monitored. Further research
      might elucidate the sex differences in VZV specific GMC.

PMID- 23973249
TI  - Serotonergic genes and suicidal ideation 2 weeks and 1 year after stroke in
      Korea.
AB  - OBJECTIVES: Serotonergic genes are associated with suicidal behavior; this
      association has not been tested in stroke survivors, however. In this study, we
      investigated whether serotonin transporter (5-HTT) and serotonin 2a receptor (5
      HTR2a) genes were associated with suicidal ideation at 2 weeks and at 1 year
      after stroke. METHODS: A total of 286 patients were evaluated 2 weeks after
      stroke, and 222 (78%) participated in a follow-up evaluation one year later.
      Suicidal ideation was ascertained using the "suicidal thoughts" item of the
      Montgomery and Asberg Depression Rating Scale. Associations between suicidal
      ideation and 5-HTTLPR, STin2 VNTR, 5-HTR2a 1438A/G, and 5-HTR2a 102T/C genotypes
      were estimated using logistic regression models, and gene-gene interactions were
      investigated using the generalized multifactor dimensionality reduction method
      after adjustment for potential covariates, including depression. RESULTS: The 5
      HTR2a 1438 A/A genotype was significantly associated with suicidal ideation 2
      weeks after stroke, before and after statistical adjustment. The 5-HTTLPR short
      allele was associated with suicidal ideation 2 weeks after stroke, although the
      significance of this finding was not evident after adjustment. No significant
      associations were observed between any genotype and suicidal ideation one year
      after stroke. No significant gene-gene interactions were detected. CONCLUSIONS:
      Individuals with the 5-HTR2a 1438 A/A genotype were more susceptible to suicidal
      ideation 2 weeks after stroke. Careful evaluation and management are indicated
      for those with increased genetic vulnerability, particularly during the acute
      phase of stroke.

PMID- 23973250
TI  - Deliberating clinical research with cognitively impaired older people and their
      relatives: an ethical add-on study to the protocol "Effects of Temporary
      Discontinuation of Antihypertensive Treatment in the Elderly (DANTE) with
      Cognitive Impairment".
AB  - OBJECTIVES: To explore the decision-making process involving elderly subjects
      with mild cognitive impairment and a relative when asked to participate in a
      clinical trial. DESIGN, SETTING, AND PARTICIPANTS: In this qualitative study, we
      investigated the decision-making process during the informed consent
      conversations between the researchers of a clinical trial and 18 persons aged 75
      years and older, with a Mini-Mental State Examination score >=21 and <=27. This
      assessment was performed by both observation and a standardized interview with
      the older person and a close relative who could act as a proxy (surrogate)
      decision maker, if necessary. The informed consent conversation and procedure
      took place at the home of the potential participants. MEASUREMENTS: Videotapes or
      audiotapes were transcribed and analyzed by using coding schemes. RESULTS: The
      participants were able to formulate substantial reasons why they would want to
      participate in the clinical trial. Willingness to help others and contribute to
      medical knowledge, combined with the absence of substantial risks, were
      predominant reasons for participation. Most older subjects did consult their
      relatives, who generally considered them capable of deciding for themselves.
      CONCLUSIONS: Notwithstanding their (mild) cognitive impairment, these older
      subjects were able to formulate substantiated reasons for participation in a
      clinical trial. Thus, it is plausible that they were capable of making this
      decision themselves, which was affirmed by their relatives. Recognition of the
      desire to contribute unselfishly to research that might benefit others has
      important implications for future clinical research conducted in older people
      with mild cognitive impairment.

PMID- 23973251
TI  - SLC6A4 polymorphisms and age of onset in late-life depression on treatment
      outcomes with citalopram: a Sequenced Treatment Alternatives to Relieve
      Depression (STAR*D) report.
AB  - OBJECTIVE: Age at onset of first major depressive episode (MDE) does not
      necessarily translate into different treatment outcomes to antidepressants in
      late-life depression. The influence of genetic variants may affect this
      relationship. DESIGN: Post hoc data set analysis of the association between
      variants in the promoter region (indel, rs25531) and within intron 2 (Stin2 VNTR)
      of the SCL6A4 gene and treatment outcomes among older participants in the first
      treatment arm of the Sequenced Treatment Alternatives to Relieve Depression trial
      (STAR*D). SETTING: Participants were enrolled from 23 psychiatric and 18 primary
      care settings. PARTICIPANTS: Two hundred twenty-one, white non-Hispanic subjects,
      aged 60 to 75 years, with 16-item Quick Inventory of Depressive Symptomatology
      Clinician Rating (QIDS-CR16) initial score >=10, and who remained in the study
      for at least 6 weeks, were genotyped. INTERVENTION: Citalopram treatment for up
      to 14 weeks. MEASUREMENTS: Main outcome was remission rate defined as a score of
      <=5 on the QIDS-CR16. Response was a secondary outcome defined as a reduction of
      >=50% of baseline QIDS-CR16. RESULTS: Polymorphism in the indel promoter region
      was associated with remission among subjects whose first lifetime episode of
      major depression occurred later than age 55. In this group, subjects with L/L
      genotype had significantly higher remission (80% versus 43%) compared to those
      subjects with any other indel promoter genotype. Multivariate analysis
      demonstrated that the genetic effect of the indel promoter region on remission
      increases along with age at onset of MDE. CONCLUSIONS: Variants in the indel
      promoter region of the SLC6A4 gene have a more robust effect to antidepressant
      outcome among older subjects who experienced their first MDE at a later age. The
      mechanism of action of these variants remains to be determined.

PMID- 23973252
TI  - Frailty and depression in older adults: a high-risk clinical population.
AB  - OBJECTIVE: To identify salient characteristics of frailty that increase risk of
      death in depressed elders. METHODS: Data were from the Nordic Research on Ageing
      Study from research sites in Denmark, Sweden, and Finland. Participants were
      1,027 adults aged 75 years (436 men and 591 women). Time of death was obtained,
      providing a maximum survival time of 11.08 years (initial evaluation took place
      between 1988 and 1991). RESULTS: Depressed elders showed greater baseline
      impairments in each frailty characteristic (gait speed, grip strength, physical
      activity levels, and fatigue). Simultaneous models including all four frailty
      characteristics showed slow gait speed (hazard ratio: 1.84; 95% confidence
      interval: 1.05-3.21) and fatigue (hazard ratio: 1.94; 95% confidence interval:
      1.11-3.40) associated with faster progression to death in depressed women; none
      of the frailty characteristics in the simultaneous model was associated with
      death in depressed men. In women, the effect of impaired gait speed on mortality
      rates nearly doubled when depression was present (nondepressed women: no gait
      impairment = 26%; slow gait = 40%; depressed women: no gait impairment = 32%;
      slow gait = 58%). A similar pattern was observed for fatigue. CONCLUSION: The
      confluence of specific characteristics of frailty (fatigue and slow gait speed)
      and depressive illness is associated with an increased risk of death in older
      adults; this association is particularly strong in older depressed women. Future
      research should investigate whether multimodal interventions targeting depressive
      illness, mobility deficits, and fatigue can decrease mortality and improve
      quality of life in older depressed individuals with characteristics of the
      syndrome of frailty.

PMID- 23973254
TI  - Twelve-year history of late-life depression and subsequent feelings to God.
AB  - OBJECTIVES: Growing evidence shows several possible relations between
      religiousness and late-life depression. Emotional aspects of religiousness such
      as facets of the perceived relationship with God can be crucial in this
      connection. The aim of the current study was to examine the association between
      the course of late-life depression and feelings about God and religious coping.
      DESIGN: Longitudinal survey study; naturalistic; 12-year follow-up. SETTING:
      Longitudinal Aging Study Amsterdam; population-based, in three regions in The
      Netherlands. PARTICIPANTS: A subsample of 343 respondents (mean age: 77.2 years),
      including all respondents with high levels of depressive symptoms at any
      measurement cycle between 1992 and 2003 (assessed by using the Center for
      Epidemiologic Studies Depression Scale and the Diagnostic Interview Schedule) and
      a random sample of nondepressed respondents who completed a postal questionnaire
      in 2005. MEASUREMENTS: Scales on God Image and Religious Coping. Twelve-year
      depression course trajectories serve as predicting variables and are specified
      according to recency and seriousness. RESULTS: Persistent and emergent depression
      are significantly associated with fear of God, feeling wronged by God, and
      negative religious coping. In terms of negative religious coping, significant
      associations were observed after adjustment for concurrent depression with a
      history of repeated minor depression and previous major depression. CONCLUSIONS:
      Late-life depression seems to maintain a pervasive relationship over time with
      affective aspects of religiousness. Religious feelings may parallel the symptoms
      of anhedonia or a dysphoric mood and could represent the experience of an
      existential void.

PMID- 23973253
TI  - Alcohol use, anxiety, and insomnia in older adults with generalized anxiety
      disorder.
AB  - OBJECTIVES: To examine alcohol consumption among older primary care patients with
      generalized anxiety disorder (GAD); its relationship to demographic variables,
      insomnia, worry, and anxiety; and its moderating role on the anxiety-insomnia
      relationship. We expected alcohol use to be similar to previous reports,
      correlate with higher anxiety and insomnia, and worsen the anxiety-insomnia
      relationship. DESIGN: Baseline data from a randomized controlled trial. SETTING:
      Michael E. DeBakey VA Medical Center and Baylor College of Medicine.
      PARTICIPANTS: 223 patients, 60 years and older, with GAD. MEASUREMENTS: Frequency
      of alcohol use, insomnia (Insomnia Severity Index), worry (Penn State Worry
      Questionnaire - Abbreviated, Generalized Anxiety Disorder Severity Scale), and
      anxiety (State-Trait Anxiety Inventory - Trait subscale, Structured Interview
      Guide for the Hamilton Anxiety Rating Scale [SIGH-A]). RESULTS: Most patients
      endorsed alcohol use, but frequency was low. Presence and frequency were greater
      than in previous reports of primary care samples. Alcohol use was associated with
      higher education, female gender, less severe insomnia, and lower worry
      (Generalized Anxiety Disorder Severity Scale) and anxiety (State-Trait Anxiety
      Inventory-Trait subscale; SIGH-A). Whites reported more drinks/week than African
      Americans. More drinks/week were associated with higher education and lower
      anxiety (SIGH-A). Weaker relationships between worry/anxiety and insomnia
      occurred for those drinking. Drink frequency moderated the positive association
      between the Penn State Worry Questionnaire-Abbreviated and insomnia, which was
      lower with higher frequency of drinking. CONCLUSIONS: Older adults with GAD use
      alcohol at an increased rate, but mild to moderate drinkers do not experience
      sleep difficulties. A modest amount of alcohol may minimize the association
      between anxiety/worry and insomnia among this group.

PMID- 23973255
TI  - Changes in DNA methylation of erythroid-specific genes in K562 cells exposed to
      phenol and hydroquinone.
AB  - Benzene is a common occupational hazard as well as a widespread pollutant. Its
      metabolites play important roles in its toxicity to the hematopoietic system, but
      little is known about how benzene metabolites affect erythropoiesis. Our previous
      study demonstrated that benzene metabolites, including phenol and hydroquinone,
      inhibited hemin-induced erythroid differentiation of K562 cells. In present
      study, to elucidate the role of DNA methylation in benzene metabolites-induced
      inhibition on erythroid differentiation, it was investigated whether DNA
      methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-aza-CdR), was able to
      prevent benzene metabolites inhibiting hemin-induced erythroid differentiation in
      K562 cells, and the methylation levels of erythroid-specific genes in benzene
      metabolites-treated K562 cells were analyzed by Quantitative MassARRAY
      methylation analysis platform. It was found that treatment of K562 cells with 5
      aza-CdR completely prevented phenol and hydroquinone inhibiting hemin-induced
      hemoglobin synthesis and hemin-induced expression of erythroid specific genes,
      including alpha- and beta-globin, erythroid porphobilinogen deaminase and GATA
      binding protein 1 (GATA-1). Consistently, the exposure to benzene metabolites
      caused an increase in DNA methylation levels at a few CpG sites in some erythroid
      specific genes, including alpha-globin gene and alpha-cluster HS40 element, beta
      globin gene and HS core sequence in LCR of beta-globin gene cluster, erythroid
      porphobilinogen deaminase gene, and GATA-1 gene. These results indicated that DNA
      methylation played a role in benzene metabolites inhibiting hemin-induced
      erythroid differentiation of K562 cells via down-regulating transcription of some
      erythroid related genes. 

PMID- 23973256
TI  - PKCE mediates serine phosphorylation of connexin43 induced by
      lysophosphatidylcholine in neonatal rat cardiomyocytes.
AB  - Lysophosphatidylcholine (LPC) is a potent pro-arrhythmic derivative of the
      membrane phosphotidylcholine, which is accumulated in heart tissues during
      cardiac ischemia. However, the cellular mechanism underlying LPC-induced
      cardiomyocyte damage remains to be elucidated. This study focuses on the effects
      of LPC on cardiomyocyte gap junction. At 30MUM, LPC decreased the spontaneous
      contraction rates of cardiomyocytes, and caused arrhythmic contraction without
      affecting cell viability. Connexin43 (Cx43) was seen as large plaques at cell
      junctions in control cells, whereas upon LPC treatment, the intensity of Cx43
      staining was decreased in a concentration-sensitive manner and Cx43 staining
      appeared as tiny dots at cell junctions with a corresponding increase in
      cytoplasmic punctate staining. This distributional change of Cx43 was accompanied
      by an impairment of the gap junction intercellular communication (GJIC). Further,
      LPC treatment induced protein kinase C (PKC) activation, and PKC-dependent Cx43
      phosphorylation at serine (Ser) 368. Pre-treatment with a specific PKCE
      inhibitor, eV1-2, prevented the LPC-induced Cx43 phosphorylation at Ser368 and
      the loss of Cx43 from gap junctions, both of which may disturb GJIC functions.
      Furthermore, siRNA knockdown of PKCE in H9c2 cells prevented LPC-induced serine
      phosphorylation of Cx43, confirming the role of PKCE in Cx43 serine
      phosphorylation. Double labeling immunofluorescence showed that LPC increased the
      colocalization of Cx43 with ubiquitin, and pretreatment with MG132 effectively
      prevented LPC-induced gap junction disassembly. LPC increased the ubiquitination
      of Cx43, which was blocked by eV1-2 pretreatment, suggesting that LPC accelerated
      the intracellular degradation of Cx43 via the ubiquitin-proteasomal pathway. It
      can be concluded that LPC destroyed the structure and function of gap junctions
      via PKCE-mediated serine phosphorylation of Cx43. PKCE inhibitors might therefore
      be effective in prevention of LPC-related diseases. 

PMID- 23973257
TI  - Electro-peroxone treatment of Orange II dye wastewater.
AB  - Degradation of a synthetic azo dye, Orange II, by electro-peroxone (E-peroxone)
      treatment was investigated. During the E-peroxone process, ozone generator
      effluent (O2 and O3 gas mixture) was continuously sparged into an electrolysis
      reactor, which was equipped with a carbon-polytetrafluorethylene (carbon-PTFE)
      cathode to electrochemically convert the sparged O2 to H2O2. The in-situ
      generated H2O2 then reacted with the sparged O3 to produce *OH, which can oxidize
      ozone-refractory organic pollutants effectively. Thus, by simply combining
      conventional ozonation and electrolysis processes, and using a cathode that can
      effectively convert O2 to H2O2, the E-peroxone process degraded Orange II much
      more effectively than the two processes individually. Complete decolorization and
      95.7% total organic carbon (TOC) mineralization were obtained after 4 and 45 min
      of the E-peroxone treatment, respectively. In comparison, only 55.6 and 15.3% TOC
      were mineralized after 90 min of the individual ozonation and electrolysis
      treatments, respectively. In addition to its high efficiency, the E-peroxone
      process was effective over a wide range of pH (3-10) and did not produce any
      secondary pollutants. The E-peroxone process can thus provide an effective and
      environmentally-friendly alternative for wastewater treatment.

PMID- 23973258
TI  - Uranium behaviour in an estuary polluted by mining and industrial effluents: the
      Ria of Huelva (SW of Spain).
AB  - This paper describes a comprehensive study of the behaviour of U in the Ria of
      Huelva estuary, formed by the Tinto and Odiel rivers. This ecosystem is
      conditioned by two hydrochemical facts: one connected with the acid mining
      drainage (AMD) generated in the first section of the river basins, and another
      one related to the fertilizer industry located at the estuary. AMD gives a
      singular character to these rivers; low pH and high redox potential that keep
      high amounts of toxic elements and radionuclides in dissolution. Most of the data
      for dissolved U in estuaries indicate conservative mixing, but there are examples
      of non-conservative behaviour attributed to oxidation/reduction processes or
      solubility variations. In the Ria of Huelva estuary the U shows a non
      conservative behaviour due to solubility changes produced by variations in the
      pH. A complete removal of riverine dissolved U is observed in a pH range of 4-6.
      At higher pH values, U release from suspended matter, and probably also from
      sediments into the dissolved phase is found. 

PMID- 23973259
TI  - Physiological responses of the southern king crab, Lithodes santolla (Decapoda:
      Lithodidae), to aerial exposure.
AB  - The recent demand for live seafood has made Lithodes santolla a potential
      candidate for the live crab market. Since live transport implies long aerial
      exposure times, the present study determined the tolerance of L. santolla to
      aerial exposure and also explored the physiological status of L. santolla after
      six different aerial exposure times: 0, 10, 20, 30, 40 and 50h. No mortalities
      were recorded during emersion periods shorter than 40 h, however, all hemolymph
      parameters were modulated by aerial exposure. Hemolymph dissolved oxygen and pH
      were inversely related with the aerial exposure time (-0.016 mg L(-1) h(-1) and 
      0.018 h(-1), respectively), while oxyhemocyanin and hemolymph protein were
      positively correlated (0.006 mmol L(-1) h(-1) and 0.487 mg mL(-1) h(-1),
      respectively). Oxygen consumption at re-immersion was affected by aerial exposure
      time, with low values in animals emersed for longer than 30 h. We postulate that
      the unexpected high tolerance of L. santolla to aerial exposure is mainly related
      to adaptations to hypoxia, developed to overcome hypoxic events in their natural
      environment in deep water. The present findings are not only important for
      understanding L. santolla's physiology, but also provide the first evaluation of
      the potential marketing of southern king crab as live seafood.

PMID- 23973260
TI  - MALAT-1 interacts with hnRNP C in cell cycle regulation.
AB  - As a conserved non-coding RNA gene, transcripts of MALAT-1 localize predominately
      in the nucleus. However in G2/M cell cycle phase, MALAT-1 transcripts were
      surprisingly found to translocate from the nucleus into the cytoplasm.
      Investigation also found that in this process MALAT-1 interacts with an abundant
      nuclear factor, hnRNP C protein. Using a loss-of-function assay, we found that
      down-regulation of MALAT-1 expression compromised the cytoplasmic translocation
      of hnRNP C in the G2/M phase and resulted in G2/M arrest. In addition to
      characterize the physiological interaction between MALAT-1 and hnRNP C, our study
      also highlights the role of MALAT-1 in cell cycle regulation. 

PMID- 23973261
TI  - Fast and slow dynamics of malaria model with relapse.
AB  - Two mathematical models of malaria with relapse are studied. When the vector
      population size is constant, complete analyses of the dynamics are conducted. The
      geometric singular perturbation theory is used to analyze the full dynamics. On
      the critical manifold, from next generation matrix method, we obtain the basic
      reproduction number. The global stability of disease-free equilibrium and the
      uniformly persistence of malaria have also been analyzed. While the vector
      population size is variable, the basic reproduction number and the stability of
      disease-free as well as the malaria-infected equilibrium have been obtained in a
      similar way. Some numerical simulations are also given. 

PMID- 23973262
TI  - Significance of TP53 mutations determined by next-generation "deep" sequencing in
      prognosis of estrogen receptor-positive breast cancer.
AB  - Next-generation "deep" sequencing (NGS) was used for the mutational analysis of
      TP53, and a DNA microarray was used for the determination of the TP53 mutation
      associated gene expression signature (TP53 GES) in 115 estrogen receptor (ER)
      positive breast cancers. NGS detected 27 TP53 mutations, of which 20 were also
      detected by Sanger sequencing (SS) and seven were detected only by NGS. A
      significantly higher number of mutant alleles (33.9%) was detected in the tumors
      with TP53 mutations detected by SS compared with those with TP53 mutations
      detected only by NGS (11.1%). The TP53 mutations detected by NGS were more
      significantly associated with a large tumor size, a high histological grade,
      progesterone receptor-negativity, and HER2-positivity compared with those
      detected by SS. The TP53 mutations detected by SS, but not those detected by NGS
      or the p53 immunohistochemistry, exhibited a significant association with poor
      prognosis. In addition, the TP53 GES more clearly differentiated low- from high
      risk patients for relapse than the TP53 mutations detected by SS, regardless of
      the other conventional prognostic factors. Thus, NGS is more sensitive for the
      detection of TP53 mutations, but the prognostic significance of these mutations
      could not be demonstrated. In contrast, the TP53 GES proved to be a powerful
      prognostic indicator for ER-positive tumors. 

PMID- 23973263
TI  - Differential drug responses of circulating tumor cells within patient blood.
AB  - Personalized medicine holds great promise for cancer treatment, with the
      potential to address challenges associated with drug sensitivity and interpatient
      variability. Circulating tumor cells (CTC) can be useful for screening cancer
      drugs as they may reflect the severity and heterogeneity of primary tumors. Here
      we present a platform for rapidly evaluating individualized drug susceptibility.
      Treatment efficacy is evaluated directly in blood, employing a relevant
      environment for drug administration, and assessed by comparison of CTC counts in
      treated and control samples. Multiple drugs at varying concentrations are
      evaluated simultaneously to predict an appropriate therapy for individual
      patients. 

PMID- 23973264
TI  - Deadly crosstalk: Notch signaling at the intersection of EMT and cancer stem
      cells.
AB  - Notch signaling is an evolutionarily conserved pathway involved in cell fate
      control during development, stem cell self-renewal and postnatal tissue
      differentiation. Roles for Notch in carcinogenesis, in the biology of cancer stem
      cells, tumor angiogenesis and epithelial-to-mesenchymal transition (EMT) have
      been reported. This mini-review describes the role of Notch signaling
      deregulation in EMT and tumor aggressiveness. We describe how accumulated
      evidence suggests that Notch inhibition is an attractive strategy for the
      treatment of several cancers, at least in part because of its potential to
      reverse or prevent EMT. 

PMID- 23973265
TI  - Critiquing blind dating: the dangers of over-confident date estimates in
      comparative genomics.
AB  - Phylogenomic advances provide more rigorous estimates for the timing of
      evolutionary divergences than previously available (e.g., Bayesian relaxed-clock
      estimates with soft fossil constraints). However, because many family-level
      clades and higher, as well as model species within those clades, have not been
      included in phylogenomic studies, the literature presents temporal estimates
      likely harboring substantial errors. Blindly using such dates can substantially
      retard scientific advancement. We suggest a way forward by conducting analyses
      that minimize prior assumptions and use large datasets, and demonstrate how using
      such a phylogenomic approach can lead to significantly more parsimonious
      conclusions without a good fossil record. We suggest that such an approach calls
      for research into the biological causes of conflict between molecular and fossil
      signatures. 

PMID- 23973267
TI  - Scalp cooling to prevent alopecia after chemotherapy can be considered safe in
      patients with breast cancer.
AB  - With modern scalp cooling equipment cytotoxic damage of hair root cells can be
      prevented in half of the patients with cancer at high risk of alopecia. However,
      traditionally doubt has existed whether scalp cooling might facilitate hiding and
      disseminating scalp skin metastases and thus decrease survival. We discuss this
      risk using frequency data on metastases in breast cancer from observational and
      autopsy studies and the Munich cancer registry. They showed the incidence of
      scalp skin metastases to be very low and not differ between scalp-cooled (0.04
      1%) and non scalp-cooled (0.03-3%) patients with breast cancer and in need of
      chemotherapy. We found it rather unlikely that the incidence of scalp skin
      metastases might increase at all after scalp cooling, whereas a very small
      proportion of patients receiving chemotherapy are at risk to develop metastases
      at this site. Scalp cooling can thus safely be offered to patients treated with
      alopecia-inducing chemotherapy. 

PMID- 23973268
TI  - Efficacy of miglustat in Niemann-Pick C disease: a single centre experience.
AB  - Niemann-Pick disease type C (NPC) is a lysosomal storage disease characterized by
      progressive neurological degeneration. Miglustat is the first approved specific
      therapy and its efficacy in stabilizing or slowing disease progression has been
      demonstrated in previous studies. We evaluated data from 10 NPC patients treated
      with Miglustat in a single study centre. All disease manifestations were assessed
      and patients were stratified according to age at onset of neurological symptoms.
      Neurological data were recorded by using a modified version of the NP-C
      disability scale; a "composite score" and a "mean annual change" were calculated
      to evaluate disease progression. We observed a mean annual change of the
      composite score of 0.04 in our cohort, indicating slower progression of
      neurological symptoms if compared with the natural history of the disease. The
      evidence of slower disease evolution in patients treated with Miglustat suits
      with previous data and here it is also emphasized by the comparison between
      disease progression in two early-infantile onset patients receiving different
      Miglustat dosages. Evaluation of the mean annual change for individual subgroups
      of patients evidenced minor values in juvenile patients, highlighting better
      response in such class of patients. Among individual neurological parameters,
      swallowing showed the minor mean annual change (0.02), indicating better response
      to therapy. We underline the importance of using a standardized disability scale
      to quantify and compare neurological features and their evolution over time. 

PMID- 23973266
TI  - Endocytosis and intracellular processing of BODIPY-sphingomyelin by murine CATH.a
      neurons.
AB  - Neuronal sphingolipids (SL) play important roles during axonal extension,
      neurotrophic receptor signaling and neurotransmitter release. Many of these
      signaling pathways depend on the presence of specialized membrane microdomains
      termed lipid rafts. Sphingomyelin (SM), one of the main raft constituents, can be
      formed de novo or supplied from exogenous sources. The present study aimed to
      characterize fluorescently-labeled SL turnover in a murine neuronal cell line
      (CATH.a). Our results demonstrate that at 4 degrees C exogenously added BODIPY-SM
      accumulates exclusively at the plasma membrane. Treatment of cells with bacterial
      sphingomyelinase (SMase) and back-exchange experiments revealed that 55-67% of
      BODIPY-SM resides in the outer leaflet of the plasma membrane. Endocytosis of
      BODIPY-SM occurs via caveolae with part of internalized BODIPY-fluorescence
      ending up in the Golgi and the ER. Following endocytosis BODIPY-SM undergoes
      hydrolysis, a reaction substantially faster than BODIPY-SM synthesis from BODIPY
      ceramide. RNAi demonstrated that both, acid (a)SMase and neutral (n)SMases
      contribute to BODIPY-SM hydrolysis. Finally, high-density lipoprotein (HDL)
      associated BODIPY-SM was efficiently taken up by CATH.a cells. Our findings
      indicate that endocytosis of exogenous SM occurs almost exclusively via caveolin
      dependent pathways, that both, a- and nSMases equally contribute to neuronal SM
      turnover and that HDL-like particles might represent physiological SM
      carriers/donors in the brain. 

PMID- 23973269
TI  - The impact of informal care for patients with Pompe disease: an application of
      the CarerQol instrument.
AB  - BACKGROUND: Patients with Pompe disease, a rare progressive neuromuscular
      disorder, receive a considerable amount of informal care. In this study, we
      examined the impact of providing informal care to patients with Pompe disease.
      METHODS: Caregivers were administered various instruments, which measured the
      (impact of) informal care in the context of Pompe disease. Patients' quality of
      life and use of a wheelchair and respiratory support were used to investigate the
      impact of disease severity on the burden and well-being of caregivers. RESULTS:
      Of all Dutch patients with Pompe disease, 88 indicated to receive informal care,
      of which 67 (76%; 67 caregivers) participated in this study. On average,
      caregivers provided 17.7 hours of informal care per week. Higher disease burden
      was associated with more hours of informal care. Caregivers experienced burden
      due to caregiving. Half of the informal caregivers reported mental health
      problems and problems with daily activities due to providing informal care.
      Physical health problems occurred in 40% of informal caregivers. Caregiver burden
      was higher for patients with a lower quality of life and for wheelchair dependent
      patients. Burden was not associated with respiratory support. Caregivers reported
      deriving personal fulfillment from caregiving and, on average, would become
      unhappier if someone else were to take over their care activities. CONCLUSIONS:
      The provision of informal care causes burden to caregivers. However, caregivers
      also value caring for their loved ones themselves. The study may help physicians
      and policy makers to design measures to support informal caregivers.

PMID- 23973272
TI  - An innovative portal for rare genetic diseases research: the semantic
      Diseasecard.
AB  - Advances in "omics" hardware and software technologies are bringing rare diseases
      research back from the sidelines. Whereas in the past these disorders were seldom
      considered relevant, in the era of whole genome sequencing the direct connections
      between rare phenotypes and a reduced set of genes are of vital relevance. This
      increased interest in rare genetic diseases research is pushing forward
      investment and effort towards the creation of software in the field, and
      leveraging the wealth of available life sciences data. Alas, most of these tools
      target one or more rare diseases, are focused solely on a single type of user, or
      are limited to the most relevant scientific breakthroughs for a specific niche.
      Furthermore, despite some high quality efforts, the ever-growing number of
      resources, databases, services and applications is still a burden to this area.
      Hence, there is a clear interest in new strategies to deliver a holistic
      perspective over the entire rare genetic diseases research domain. This is
      Diseasecard's reasoning, to build a true lightweight knowledge base covering rare
      genetic diseases. Developed with the latest semantic web technologies, this
      portal delivers unified access to a comprehensive network for researchers,
      clinicians, patients and bioinformatics developers. With in-context access
      covering over 20 distinct heterogeneous resources, Diseasecard's workspace
      provides access to the most relevant scientific knowledge regarding a given
      disorder, whether through direct common identifiers or through full-text search
      over all connected resources. In addition to its user-oriented features,
      Diseasecard's semantic knowledge base is also available for direct querying,
      enabling everyone to include rare genetic diseases knowledge in new or existing
      information systems. Diseasecard is publicly available at
      http://bioinformatics.ua.pt/diseasecard/. 

PMID- 23973270
TI  - Decidual cell regulation of natural killer cell-recruiting chemokines:
      implications for the pathogenesis and prediction of preeclampsia.
AB  - First trimester human decidua is composed of decidual cells, CD56(bright)CD16(-)
      decidual natural killer (dNK) cells, and macrophages. Decidual cells incubated
      with NK cell-derived IFN-gamma and either macrophage-derived TNF-alpha or IL
      1beta synergistically enhanced mRNA and protein expression of IP-10 and I-TAC.
      Both chemokines recruit CXCR3-expressing NK cells. This synergy required IFN
      gamma receptor 1 and 2 mediation via JAK/STAT and NFkappaB signaling pathways.
      However, synergy was not observed on neutrophil, monocyte, and NK cell-recruiting
      chemokines. Immunostaining of first trimester decidua localized IP-10, I-TAC, IFN
      gammaR1, and -R2 to vimentin-positive decidual cells versus cytokeratin-positive
      interstitial trophoblasts. Flow cytometry identified high CXCR3 levels on dNK
      cells and minority peripheral CD56(bright)CD16(-) pNK cells and intermediate
      CXCR3 levels on the majority of CD56(dim)CD16(+) pNK cells. Incubation of pNK
      cells with either IP-10 or I-TAC elicited concentration-dependent enhanced CXCR3
      levels and migration of both pNK cell subsets that peaked at 10 ng/mL, whereas
      each chemokine at a concentration of 50 ng/mL inhibited CXCR3 expression and pNK
      cell migration. Deciduae from women with preeclampsia, a leading cause of
      maternal and fetal morbidity and mortality, displayed significantly lower dNK
      cell numbers and higher IP-10 and I-TAC levels versus gestational age-matched
      controls. Significantly elevated IP-10 levels in first trimester sera from women
      eventually developing preeclampsia compared with controls, identifying IP-10 as a
      novel, robust early predictor of preeclampsia. 

PMID- 23973273
TI  - A methodology for extending domain coverage in SemRep.
AB  - We describe a domain-independent methodology to extend SemRep coverage beyond the
      biomedical domain. SemRep, a natural language processing application originally
      designed for biomedical texts, uses the knowledge sources provided by the Unified
      Medical Language System (UMLS(c)). Ontological and terminological extensions to
      the system are needed in order to support other areas of knowledge. We extended
      SemRep's application by developing a semantic representation of a previously
      unsupported domain. This was achieved by adapting well-known ontology engineering
      phases and integrating them with the UMLS knowledge sources on which SemRep
      crucially depends. While the process to extend SemRep coverage has been
      successfully applied in earlier projects, this paper presents in detail the step
      wise approach we followed and the mechanisms implemented. A case study in the
      field of medical informatics illustrates how the ontology engineering phases have
      been adapted for optimal integration with the UMLS. We provide qualitative and
      quantitative results, which indicate the validity and usefulness of our
      methodology.

PMID- 23973274
TI  - Quantitative evaluation of the outcomes of revascularization procedures for
      peripheral arterial disease using indocyanine green angiography.
AB  - OBJECTIVES: We performed indocyanine green angiography (ICGA) in patients with
      peripheral arterial disease (PAD), and established a method for the quantitative
      measurement of appropriate parameters to assess peripheral perfusion and the
      applicability of ICGA tests. METHODS: Twenty-one patients with PAD underwent
      revascularization procedures with pre- and postinterventional ICGA tests. The
      ICGA parameters, which included the magnitude of intensity of indocyanine green,
      the time to maximum intensity, and the time from fluorescence onset to half the
      maximum intensity (T1/2) were compared with the ankle-brachial pressure index,
      toe -brachial pressure index, and toe pressure. We evaluated these parameters for
      regions of interest (ROIs). RESULTS: T1/2 was the strongest parameter among all
      parameters of the ICGA tests. ROI 3, which included the distal region of the
      first metatarsal bone, correlated more significantly with the traditional
      measurements than the other ROIs. A value of T1/2 >20 seconds for ROI 3 was
      significantly correlated with a toe pressure of <50 mmHg (sensitivity: 0.77,
      specificity: 0.80). CONCLUSIONS: ICGA can be used to assess peripheral tissue
      perfusion. By measuring the value of T1/2 in ROI 3, ICGA tests can be used to
      evaluate the outcomes of revascularization procedures.

PMID- 23973276
TI  - Interventions for carotid stenosis: new evidence.

PMID- 23973275
TI  - Delay prior to expedited carotid endarterectomy: a prospective audit of practice.
AB  - OBJECTIVES: To identify reasons for delay before carotid endarterectomy (CEA) in
      a reconfigured "fast-track" system where patients were admitted from the TIA
      (transient ischaemic attack) Clinic for urgent CEA. METHODS: Prospective audit in
      89 recently symptomatic patients. RESULTS: Ten patients (11%) suffered recurrent
      symptoms between admission and surgery. Two strokes were sufficiently severe that
      CEA was cancelled. The median delay from index symptom to CEA was 8 days. 74/87
      (85%) underwent CEA <14 days from the index symptom; 39/87 (45%) within 7 days.
      Forty-five (51%) were ready for CEA <24 hours of admission; 74 (83%) <72 hours.
      The most common reasons for delay to CEA were logistical, especially a failure to
      plan for access to weekend operating. Two-thirds of the Tuesday/Friday theatre
      lists that were reserved for urgent CEAs were actually used for CEA; 27 (33%)
      were not used for CEA but were utilized for another vascular procedure, and five
      (4%) were cancelled the day before and went unused. CONCLUSIONS: The vast
      majority of patients (85%) underwent CEA <14 days from the index symptom, but 11%
      still suffered recurrent symptoms prior to surgery. Transferring patients
      directly from the TIA Clinic reduced overall delays, but Vascular Units adopting
      such an approach might then be vulnerable to criticisms regarding prolonged
      lengths of pre-operative in-patient stay while patients were worked up for
      theatre. Protected theatre lists both optimized (and delayed) access to CEA, but
      the most important cause of delay was that we had not planned for weekend
      operating using specialist anaesthetic and theatre staff.

PMID- 23973277
TI  - Near-infrared spectroscopy to indicate selective shunt use during carotid
      endarterectomy.
AB  - OBJECTIVES: This study assessed the value of cerebral near-infrared spectroscopy
      (NIRS) and transcranial Doppler (TCD) in relation to electroencephalography (EEG)
      changes for the detection of cerebral hypoperfusion necessitating shunt placement
      during carotid endarterectomy (CEA). METHODS: This was a prospective cohort
      study. Patients with a sufficient TCD window undergoing CEA from February 2009 to
      June 2011 were included. All patients were continuously monitored with NIRS and
      EEG. An intraluminal shunt was placed, selectively determined by predefined EEG
      changes in alpha, beta, theta, or delta activity. Relative changes in regional
      cerebral oxygen saturation (rSO2) in the frontal lobe and mean blood flow
      velocity (Vmean) 30 seconds before carotid cross-clamping versus 2 minutes after
      carotid cross-clamping were related to shunt placement. Receiver operating
      characteristic curve analysis was performed to determine the optimal thresholds.
      Diagnostic values were reported as positive and negative predictive value (PPV
      and NPV). RESULTS: Of a cohort of 151 patients, 17(11%) showed EEG changes
      requiring shunt placement. The rSO2 and Vmean decreased more in the shunt group
      than in the non-shunt group (mean +/- standard error of the mean) 21 +/- 4%
      versus 7 +/- 5% and 76 +/- 6% versus 12 +/- 3%, respectively (p < .005), Receiver
      operating characteristic curve analysis revealed a threshold of 16% decrease in
      rSO2 (PPV 76% and NPV 99%) and 48% decrease in Vmean (PPV 53% and NPV 99%) as the
      optimal cut-off value to detect cerebral ischemia during CEA under general
      anesthesia. CONCLUSIONS: Compared with EEG, we found moderate PPV but high NPV
      for NIRS and TCD to detect cerebral ischemia during CEA under general anesthesia,
      meaning that both techniques independently may be suitable to exclude patients
      for unnecessary shunt use and to direct the use of selective shunting. However,
      the optimal thresholds for NIRS remain to be determined.

PMID- 23973279
TI  - Work is a four-letter word.

PMID- 23973278
TI  - Pneumatic compression device treatment of lower extremity lymphedema elicits
      improved limb volume and patient-reported outcomes.
AB  - OBJECTIVES: Examine the effectiveness of an advanced pneumatic compression device
      (APCD) in reducing limb volume (LV), and to evaluate clinician and patient
      reported outcomes. DESIGN: Device registry study. MATERIALS AND METHODS: Data
      were collected prospectively for 196 lower extremity lymphedema patients
      prescribed an APCD. Baseline and post-treatment LVs were calculated and clinical
      outcomes (skin changes, pain, and function) were assessed. Patient-reported
      outcomes and satisfaction utilizing a pre- and post-treatment survey were also
      evaluated. RESULTS: 90% of APCD-treated patients experienced a significant
      reduction in LV with 35% enjoying a reduction >10%. Mean LV reduction was 1,150
      mL or 8% (p < .0001). Greater baseline LV and BMI were strong predictors of LV
      reduction (p < .0001). Clinician assessment indicated that the majority of
      patients experienced improvement in skin fibrosis and function. Patient-reported
      outcomes showed a significant increase in ability to control lymphedema through
      APCD treatment, with an increase in function and a reduction in the interference
      of pain. 66% were "very satisfied" with the APCD treatment. CONCLUSION: APCD use
      is associated with consistent reductions in LV, with favorable patient-reported
      outcomes. Results demonstrate that reduction in LV and pain, combined with
      functional improvement and patient satisfaction can be achieved, providing
      tangible benefit for lower extremity patients.

PMID- 23973280
TI  - Unsolved issues related to human mitochondrial diseases.
AB  - Human mitochondrial diseases, defined as the diseases due to a mitochondrial
      oxidative phosphorylation defect, represent a large group of very diverse
      diseases with respect to phenotype and genetic causes. They present with many
      unsolved issues, the comprehensive analysis of which is beyond the scope of this
      review. We here essentially focus on the mechanisms underlying the diversity of
      targeted tissues, which is an important component of the large panel of these
      diseases phenotypic expression. The reproducibility of genotype/phenotype
      expression, the presence of modifying factors, and the potential causes for the
      restricted pattern of tissular expression are reviewed. Special emphasis is made
      on heteroplasmy, a specific feature of mitochondrial diseases, defined as the
      coexistence within the cell of mutant and wild type mitochondrial DNA molecules.
      Its existence permits unequal segregation during mitoses of the mitochondrial DNA
      populations and consequently heterogeneous tissue distribution of the mutation
      load. The observed tissue distributions of recurrent human mitochondrial DNA
      deleterious mutations are diverse but reproducible for a given mutation
      demonstrating that the segregation is not a random process. Its extent and
      mechanisms remain essentially unknown despite recent advances obtained in animal
      models. 

PMID- 23973281
TI  - Ultrafast interfacial solvation dynamics in specific protein DNA recognition.
AB  - An overwhelming number of structural and functional studies on specific protein
      DNA complexes reveal the existence of water molecules at the interaction
      interface. What role does the interfacial water molecules play in determining the
      specificity of association is thus a critical question. Herein, we have explored
      the dynamical role of minor groove water molecules and DNA side chain flexibility
      in lambda repressor-operator DNA interaction using well-characterized DNA minor
      groove binder dye, Hoechst 33258. The most striking finding of our studies
      reveals that the solvation time scale corresponding to the minor groove water
      molecules (~50 ps) and DNA side chain flexibility (~10 ns) remain unaltered even
      in protein-DNA complex in comparison to unbound operator DNA. The temperature
      dependent study further reveals the slower exchange of minor grove water
      molecules with bulk water in DNA-protein complex in comparison to the unbound
      DNA. Detailed structural studies including circular dichroism (CD) and Forster
      resonance energy transfer (FRET) have also been performed to elucidate the
      interaction between protein and DNA.

PMID- 23973282
TI  - Antitumour activity on extrinsic apoptotic targets of the triterpenoid maslinic
      acid in p53-deficient Caco-2 adenocarcinoma cells.
AB  - We report that a novel triterpenoid, (2a,3b)-2,3-dihydroxyolean-12-en-28-oic acid
      (maslinic acid), isolated from olive pomace from Olea europaea, triggers
      primarily the extrinsic and later the intrinsic apoptotic pathways in Caco-2
      human colon-cancer cells. Apoptosis induced by maslinic acid was confirmed by
      FACS analysis using annexine-V FICT staining. This induction of apoptosis was
      correlated with the early activation of caspase-8 and caspase-3, the activation
      of caspase-8 was also correlated with higher levels of Bid cleavage and decreased
      Bcl-2, but with no change in Bax expression. Maslinic acid also induced a
      sustained activation of c-Jun N-terminal kinase (JNK). Incubation with maslinic
      acid also resulted in the later activation of caspase-9, which, together with the
      lack of any Bax activation, suggests that the mitochondrial pathway is not
      required for apoptosis induced by maslinic acid in this cell line. In this study
      we found that the mechanism of apoptotic activation in p53-deficient Caco-2 cells
      differs significantly from that found in HT-29 cells. Natural agents able to
      activate both the extrinsic and intrinsic apoptotic pathways by avoiding the
      mitochondrial resistance mechanisms may be useful for treatment against colon
      cancer regardless of its aetiology.

PMID- 23973283
TI  - Biochemical characterisation of triose phosphate isomerase from the liver fluke
      Fasciola hepatica.
AB  - Triose phosphate isomerase (TPI) catalyses the interconversion of
      dihydroxyacetone phosphate and glyceraldehyde 3-phosphate, a reaction in the
      glycolytic pathway. TPI from the common liver fluke, Fasciola hepatica, has been
      cloned, sequenced and recombinantly expressed in Escherichia coli. The protein
      has a monomeric molecular mass of approximately 28 kDa. Crosslinking and gel
      filtration experiments demonstrated that the enzyme exists predominantly as a
      dimer in solution. F. hepatica TPI is predicted to have a beta-barrel structure
      and key active site residues (Lys-14, His-95 and Glu-165) are conserved. The
      enzyme shows remarkable stability to both proteolytic degradation and thermal
      denaturation. The melting temperature, estimated by thermal scanning fluorimetry,
      was 67  degrees C and this temperature was increased in the presence of either
      dihydroxyacetone phosphate or glyceraldehyde 3-phosphate. Kinetic studies showed
      that F. hepatica TPI demonstrates Michaelis-Menten kinetics in both directions,
      with Km values for dihydroxyacetone phosphate and glyceraldehyde 3-phosphate of
      2.3 mM and 0.66 mM respectively. Turnover numbers were estimated at 25,000 s(-1)
      for the conversion of dihydroxyacetone phosphate and 1900 s(-1) for the
      conversion of glyceraldehyde 3-phosphate. Phosphoenolpyruvate acts as a weak
      inhibitor of the enzyme. F. hepatica TPI has many features in common with
      mammalian TPI enzymes (e.g. beta-barrel structure, homodimeric nature, high
      stability and rapid kinetic turnover). Nevertheless, recent successful
      identification of specific inhibitors of TPI from other parasites, suggests that
      small differences in structure and biochemical properties could be exploited in
      the development of novel, species-specific inhibitors.

PMID- 23973284
TI  - On the existence of 'L-alanine cadmium bromide'.
AB  - It is argued that the recently reported nonlinear optical crystal L-alanine
      cadmium bromide, grown by slow solvent evaporation method at room temperature [P.
      Ilayabarathi, J. Chandrasekaran, Spectrochim. Acta 96A (2012) 684-689] is the
      well-known L-alanine crystal. The isolation of L-alanine crystal is explained due
      to fractional crystallization.

PMID- 23973285
TI  - Pharmaceuticals and personal care products found in the Great Lakes above
      concentrations of environmental concern.
AB  - The monitoring of pharmaceuticals and personal care products (PPCPs) has focused
      on the distribution in rivers and small lakes, but data regarding their
      occurrence and effects in large lake systems, such as the Great Lakes, are
      sparse. Wastewater treatment processes have not been optimized to remove influent
      PPCPs and are a major source of PPCPs in the environment. Furthermore, PPCPs are
      not currently regulated in wastewater effluent. In this experiment we evaluated
      the concentration, and corresponding risk, of PPCPs from a wastewater effluent
      source at varying distances in Lake Michigan. Fifty-four PPCPs and hormones were
      assessed on six different dates over a two-year period from surface water and
      sediment samples up to 3.2 km from a wastewater treatment plant and at two sites
      within a harbor. Thirty-two PPCPs were detected in Lake Michigan and 30 were
      detected in the sediment, with numerous PPCPs being detected up to 3.2 km away
      from the shoreline. The most frequently detected PPCPs in Lake Michigan were
      metformin, caffeine, sulfamethoxazole, and triclosan. To determine the ecological
      risk, the maximum measured environmental concentrations were compared to the
      predicted no-effect concentration and 14 PPCPs were found to be of medium or high
      ecological risk. The environmental risk of PPCPs in large lake systems, such as
      the Great Lakes, has been questioned due to high dilution; however, the
      concentrations found in this study, and their corresponding risk quotient,
      indicate a significant threat by PPCPs to the health of the Great Lakes,
      particularly near shore organisms.

PMID- 23973286
TI  - Molybdate adsorption from steel slag eluates by subsoils.
AB  - Steel slags are industrial by-products which are generated in large amounts
      worldwide, e.g. 150-230*10(6) Mg in 2012, and which are partly used for
      construction. Molybdenum (Mo) can be added during steel processing in order to
      harden the steel. The objective of this study was to evaluate the adsorption
      behaviour of molybdate (MoO4(2-)) from slag eluates in subsoils. Molybdate batch
      adsorption experiments were carried out with eluates obtained from two different
      kinds of steel slags (i) LD slag (Linz-Donawitz operation, LDS) and (ii) electric
      arc furnace slag (EAF) to assess the risk that may arise from the contamination
      of groundwater by the leaching of molybdate. Six different subsoils were chosen
      in order to provide a wide range of chemical properties (pH 4.0-7.6; dithionite
      extractable Fe 0.73-14.7 g kg(-1)). Molybdate adsorption experiments were carried
      out at the pH of the steel slag eluates (pH 11-12) as well as at pH values
      adjusted to the soil pH. The data were evaluated with the Freundlich equation.
      Molybdate adsorption exhibited a maximum near pH 4 for steel slag eluates
      adjusted to the soil pH, and decreased rapidly with increasing pH until
      adsorption was virtually zero at pH>11. Adsorption was greater for soils with
      high amounts of dithionite-extractable Fe oxides. The extent and behaviour of
      molybdate adsorption from both eluates was similar. After a reaction time of 24h,
      the pH of the EAF slag eluate was lower than that of the LD steel slag eluate,
      which was caused by different acid buffer capacities. Some soils were able to
      decrease the pH of the EAF slag eluates by about 4 pH units, enhancing the
      adsorption of molybdate. Transport simulations indicated that molybdate discharge
      is low in acidic soils.

PMID- 23973287
TI  - Spatial distribution of perfluoroalkyl acids in the Pearl River of southern
      China.
AB  - An intensive campaign was conducted in September 2012 to collect surface water
      samples along the tributaries of the Pearl River in southern China. Thirteen
      perfluoroalkyl acids (PFAAs), including perfluorocarboxylates (PFCAs, C4-C11) and
      perfluorosulfonates (PFSAs, C4, C6-C8, and C10), were determined using high
      performance liquid chromatography/negative electrospray ionization-tandem mass
      spectrometry (HPLC/(-)ESI-MS/MS). The concentrations of total PFAAs (SigmaPFAAs)
      ranged from 3.0 to 52 ng L(-1), with an average of 19+/-12 ng L(-1). The highest
      concentrations of SigmaPFAAs were detected in the surface water of the Dong Jiang
      tributary (17-52 ng L(-1)), followed by the main stream (13-26 ng L(-1)) and the
      Sha Wan stream (3.0-4.5 ng L(-1)). Perfluorooctanoate (PFOA), perfluorobutane
      sulfonate (PFBS), and perfluorooctane sulfonate (PFOS) were the three most
      abundant PFAAs and on average accounted for 20%, 24%, and 19% of SigmaPFAAs,
      respectively. PFBS was the most abundant PFAA in the Dong Jiang tributary, and
      PFOA was the highest PFAA in the samples from the main stream of the Pearl River.
      A correlation was found between PFBS and PFOA, which suggests that both of these
      PFAAs originate from common source(s) in the region. Nevertheless, the slope of
      PFBS/PFOA was different in the different tributaries sampled, which indicates a
      spatial difference in the source profiles of the PFAAs.

PMID- 23973288
TI  - Comparison of in vivo immunomodulatory effects of intravenous and intraperitoneal
      administration of adipose-tissue mesenchymal stem cells in experimental
      autoimmune encephalomyelitis (EAE).
AB  - Due to their immunomodulatory and anti-inflammatory competence, mesenchymal stem
      cells (MSCs) have been considered as a suitable candidate for treatment of
      autoimmune diseases. Earlier studies have shown that treatment with bone marrow
      derived MSCs may modulate immune responses and reduce disease severity in
      experimental autoimmune encephalomyelitis (EAE), an animal model of multiple
      sclerosis. Here we compare the immune regulatory properties of adipose tissue
      MSCs (AT-MSCs) in two independent routes of injection; namely intraperitoneal
      (i.p.) and intravenous (i.v.). We investigated the splenic CD4+CD25+FOXP3+ T cell
      population known as regulatory T cells, by flow cytometry and their brain cell
      infiltration by hematoxylin-eosin staining in both i.p. and i.v. routes of AT-MSC
      administration. We also evaluated the inflammatory cytokine profile including IFN
      gamma and IL-17 and anti-inflammatory cytokines such as IL-4 by ELISA technique
      in both routes of cell administration. We show that the i.p. route has a more
      pronounced effect in maintaining the splenic CD4+CD25+FOXP3+ T cell population
      and increase of IL-4 secretion. We also showed that i.p. injection of cells
      resulted in lower IFN-gamma secretion and reduced cell infiltration in brain more
      effectively as compared to the i.v. route. The effects of AT-MSCs on down
      regulation of splenocyte proliferation, IL-17 secretion and alleviating the
      severity of clinical scores were similar in i.p. and i.v. routes. Our data show
      that, due to their immunomodulative and neuroprotective effects, AT-MSCs may be a
      proper candidate for stem cell based MS therapy.

PMID- 23973290
TI  - BDNF regulation of synaptic structure, function, and plasticity.

PMID- 23973291
TI  - TGF-beta superfamily member activin A acts with BDNF and erythropoietin to
      improve survival of spiral ganglion neurons in vitro.
AB  - Activins are regulators of embryogenesis, osteogenesis, hormones and neuronal
      survival. Even though activin receptor type II has been detected in spiral
      ganglion neurons (SGN), little is known about the role of activins in the inner
      ear. An activin-mediated neuroprotection is of considerable clinical interest
      since SGN are targets of electrical stimulation with cochlear implants in hearing
      impaired patients. Thus, the presence of activin type-I and type-II receptors was
      demonstrated immunocytochemically and the individual and combined effects of
      activin A, erythropoietin (EPO) and brain-derived neurotrophic factor (BDNF) on
      SGN were examined in vitro. SGN isolated from neonatal rats (P 3-5) were cultured
      in serum-free medium supplemented with activin A, BDNF and EPO. Compared to the
      negative control, survival rates of SGN were significantly improved when
      cultivated individually with activin A (p<0.001) and in combination with BDNF
      (p<0.001). Neither neurite outgrowth nor neuronal survival was influenced by the
      addition of EPO to activin A-treated neurons. However, when all three factors
      were added, a significantly (p<0.001) improved neuronal survival was observed
      (61.2+/-3.6%) compared to activin A (25.4+/-2.1%), BDNF (22.8+/-3.3%) and
      BDNF+EPO (19.2+/-1.5%). Under the influence of the EPO-inhibitors, this increase
      in neuronal survival was blocked. Acting with BDNF and EPO to promote neuronal
      survival in vitro, activin A presents an interesting factor for pharmacological
      intervention in the inner ear. The present study demonstrates a synergetic effect
      of a combined therapy with several trophic factors.

PMID- 23973292
TI  - Acetylcorynoline attenuates dopaminergic neuron degeneration and alpha-synuclein
      aggregation in animal models of Parkinson's disease.
AB  - Parkinson's disease (PD), the second most common neurodegenerative disease,
      impairs motor skills and cognitive function. To date, the drugs used for PD
      treatment provide only symptomatic relief. The identification of new drugs that
      show benefit in slowing the decline seen in PD patients is the focus of much
      current research. Acetylcorynoline is the major alkaloid component derived from
      Corydalis bungeana, a traditional Chinese medical herb. It has been shown to have
      anti-inflammatory properties, but no studies have yet described the effects of
      acetylcorynoline on PD. The aim of this study was to evaluate the potential for
      acetylcorynoline to improve PD in Caenorhabditis elegans models. In the present
      study, we used a pharmacological strain (BZ555) that expresses green fluorescent
      protein specifically in dopaminergic neurons, and a transgenic strain (OW13) that
      expresses human alpha-synuclein in muscle cells to study the antiparkinsonian
      effects of acetylcorynoline. Our experimental data showed that treatment with up
      to 10 mM acetylcorynoline does not cause toxicity in animals. Acetylcorynoline
      significantly decreases dopaminergic neuron degeneration induced by 6
      hydroxydopamine in BZ555 strain; prevents alpha-synuclein aggregation; recovers
      lipid content in OW13 strain; restores food-sensing behavior, and dopamine
      levels; and prolongs life-span in 6-hydroxydopamine-treated N2 strain, thus
      showing its potential as a possible antiparkinsonian drug. Acetylcorynoline may
      exert its effects by decreasing egl-1 expression to suppress apoptosis pathways
      and by increasing rpn5 expression to enhance the activity of proteasomes.

PMID- 23973289
TI  - RNA binding proteins in the regulation of heart development.
AB  - In vivo, RNA molecules are constantly accompanied by RNA binding proteins (RBPs),
      which are intimately involved in every step of RNA biology, including
      transcription, editing, splicing, transport and localization, stability, and
      translation. RBPs therefore have opportunities to shape gene expression at
      multiple levels. This capacity is particularly important during development, when
      dynamic chemical and physical changes give rise to complex organs and tissues.
      This review discusses RBPs in the context of heart development. Since the targets
      and functions of most RBPs--in the heart and at large--are not fully understood,
      this review focuses on the expression and roles of RBPs that have been implicated
      in specific stages of heart development or developmental pathology. RBPs are
      involved in nearly every stage of cardiogenesis, including the formation,
      morphogenesis, and maturation of the heart. A fuller understanding of the roles
      and substrates of these proteins could ultimately provide attractive targets for
      the design of therapies for congenital heart defects, cardiovascular disease, or
      cardiac tissue repair.

PMID- 23973293
TI  - Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load
      in aged APP/PS1 mice, a model of Alzheimer's disease.
AB  - Type 2 diabetes is a risk factor in the development of Alzheimer's disease (AD).
      It has been shown that insulin signalling is desensitised in the brains of AD
      patients. The incretin hormone Glucagon-like peptide-1 (GLP-1) facilitates
      insulin signalling, and long-lasting analogues such as liraglutide (Victoza((r)))
      are on the market as type 2 diabetes treatments. We have previously shown that
      liraglutide improved cognitive function, reduced amyloid plaque deposition,
      inflammation, overall APP and oligomer levels and enhanced LTP when injected
      peripherally for two months in 7 month old APPswe/PS1DeltaE9 (APP/PS1) mice. This
      showed that liraglutide has preventive effects at the early stage of AD
      development. The current study investigated whether Liraglutide would have
      restorative effects in late-stage Alzheimer's disease in mice. Accordingly, 14
      month-old APP/PS1 and littermate control mice were injected with Liraglutide (25
      nmol/kg bw) ip. for 2 months. Spatial memory was improved by Liraglutide
      treatment in APP/PS1 mice compared with APP/PS1 saline-treated mice. Overall
      plaque load was reduced by 33%, and inflammation reduced by 30%, while neuronal
      progenitor cell count in the dentate gyrus was increased by 50%. LTP was
      significantly enhanced in APP/PS1 liraglutide-treated mice compared with APP/PS1
      saline mice, corroborated with increased synapse numbers in hippocampus and
      cortex. Total brain APP and beta-amyloid oligomer levels were reduced in
      Liraglutide-treated APP/PS1 mice while IDE levels were increased. These results
      demonstrate that Liraglutide not only has preventive properties, but also can
      reverse some of the key pathological hallmarks of AD. Liraglutide is now being
      tested in clinical trials in AD patients. This article is part of the Special
      Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. 

PMID- 23973294
TI  - The nuclear accumulation of alpha-synuclein is mediated by importin alpha and
      promotes neurotoxicity by accelerating the cell cycle.
AB  - alpha-Synuclein (alpha-syn), a 14 kDa pre-synaptic protein, is widely involved in
      the Parkinson's disease (PD) pathogenesis. Recent studies have shown that the
      nuclear accumulation of alpha-syn might have a toxic effect. The main purpose of
      the present study was to explore which amino acid residues in alpha-syn are
      associated with its nuclear accumulation, the molecule(s) mediated the nuclear
      import of alpha-syn, and the role of alpha-syn accumulated in the nucleus. It has
      been noted that the nuclear import of alpha-syn may be mediated by importin alpha
      and that both the amino acid residues 1-60 and 103-140 of alpha-syn were
      indispensable for its nuclear import. After imported into the nucleus, the
      accumulated alpha-syn played a toxic role in both the PC12 cells and the C57
      mice. Furthermore, alpha-syn-nuclear localization signal-injected mice showed
      behavioral symptoms associated with PD. Further studies performed in vitro showed
      that the toxicity of alpha-syn in the nucleus might be due to an interference of
      the cell cycle. Thus, it can be concluded that alpha-syn can accumulate in
      nucleus, which is mediated by importin alpha, and promote neurotoxicity by
      accelerating the cell cycle.

PMID- 23973295
TI  - Physiological concentrations of zinc reduce taurine-activated GlyR responses to
      drugs of abuse.
AB  - Taurine is an endogenous ligand acting on glycine receptors in many brain
      regions, including the hippocampus, prefrontal cortex, and nucleus accumbens
      (nAcc). These areas also contain low concentrations of zinc, which is known to
      potentiate glycine receptor responses. Despite an increasing awareness of the
      role of the glycine receptor in the rewarding properties of drugs of abuse, the
      possible interactions of these compounds with zinc has not been thoroughly
      addressed. Two-electrode voltage-clamp electrophysiological experiments were
      performed on alpha1, alpha2 alpha1beta and alpha2beta glycine receptors expressed
      in Xenopus laevis oocytes. The effects of zinc alone, and zinc in combination
      with other positive modulators on the glycine receptor, were investigated when
      activated by the full agonist glycine versus the partial agonist taurine. Low
      concentrations of zinc enhanced responses of maximally-effective concentrations
      of taurine but not glycine. Likewise, chelation of zinc from buffers decreased
      responses of taurine- but not glycine-mediated currents. Potentiating
      concentrations of zinc decreased ethanol, isoflurane, and toluene enhancement of
      maximal taurine currents with no effects on maximal glycine currents. Our
      findings suggest that the concurrence of high concentrations of taurine and low
      concentrations of zinc attenuate the effects of additional modulators on the
      glycine receptor, and that these conditions are more representative of in vivo
      functioning than effects seen when these modulators are applied in isolation. 

PMID- 23973297
TI  - Wolf howling is mediated by relationship quality rather than underlying emotional
      stress.
AB  - While considerable research has addressed the function of animal vocalizations,
      the proximate mechanisms driving call production remain surprisingly unclear.
      Vocalizations may be driven by emotions and the physiological state evoked by
      changes in the social-ecological environment, or animals may have more control
      over their vocalizations, using them in flexible ways mediated by the animal's
      understanding of its surrounding social world. While both explanations are
      plausible and neither excludes the other, to date no study has attempted to
      experimentally investigate the influence of both emotional and cognitive factors
      on animal vocal usage. We aimed to disentangle the relative contribution of both
      mechanisms by examining howling in captive wolves. Using a separation experiment
      and by measuring cortisol levels, we specifically investigated whether howling is
      a physiological stress response to group fragmentation and whether it is driven
      by social factors, particularly relationship quality. Results showed that
      relationship quality between the howler and the leaving individual better
      predicted howling than did the current physiological state. Our findings shed
      important light on the degree to which animal vocal production can be considered
      as voluntary.

PMID- 23973296
TI  - Gcn5 and sirtuins regulate acetylation of the ribosomal protein transcription
      factor Ifh1.
AB  - BACKGROUND: In eukaryotes, ribosome biosynthesis involves the coordination of
      ribosomal RNA and ribosomal protein (RP) production. In S. cerevisiae, the
      regulation of ribosome biosynthesis occurs largely at the level of transcription.
      The transcription factor Ifh1 binds at RP genes and promotes their transcription
      when growth conditions are favorable. Although Ifh1 recruitment to RP genes has
      been characterized, little is known about the regulation of promoter-bound Ifh1.
      RESULTS: We used a novel whole-cell-extract screening approach to identify Spt7,
      a member of the SAGA transcription complex, and the RP transactivator Ifh1 as
      highly acetylated nonhistone species. We report that Ifh1 is modified by
      acetylation specifically in an N-terminal domain. These acetylations require the
      Gcn5 histone acetyltransferase and are reversed by the sirtuin deacetylases Hst1
      and Sir2. Ifh1 acetylation is regulated by rapamycin treatment and stress and
      limits the ability of Ifh1 to act as a transactivator at RP genes. CONCLUSIONS:
      Our data suggest a novel mechanism of regulation whereby Gcn5 functions to
      titrate the activity of Ifh1 following its recruitment to RP promoters to provide
      more than an all-or-nothing mode of transcriptional regulation. We provide
      insights into how the action of histone acetylation machineries converges with
      nutrient-sensing pathways to regulate important aspects of cell growth.

PMID- 23973298
TI  - Myosin XI-i links the nuclear membrane to the cytoskeleton to control nuclear
      movement and shape in Arabidopsis.
AB  - The cell nucleus communicates with the cytoplasm through a nucleocytoplasmic
      linker that maintains the shape of the nucleus and mediates its migration. In
      contrast to animal nuclei, which are moved by motor proteins (kinesins and
      dyneins) along the microtubule cytoskeleton, plant nuclei move rapidly and
      farther along an actin filament cytoskeleton. This implies that plants use a
      distinct nucleocytoplasmic linker for nuclear dynamics, although its molecular
      identity is unknown. Here, we describe a new type of nucleocytoplasmic linker
      consisting of a myosin motor and nuclear membrane proteins. In the Arabidopsis
      thaliana mutant kaku1, nuclear movement was impaired and the nuclear envelope was
      abnormally invaginated. The responsible gene was identified as myosin XI-i, which
      encodes a plant-specific myosin. Myosin XI-i is specifically localized on the
      nuclear membrane, where it physically interacts with the outer-nuclear-membrane
      proteins WIT1 and WIT2. Both WIT proteins are required for anchoring myosin XI-i
      to the nuclear membrane and for nuclear movement. A striking feature of plant
      cells is dark-induced nuclear positioning in mesophyll cells. A deficiency of
      either myosin XI-i or WIT proteins diminished dark-induced nuclear positioning.
      The unique nucleocytoplasmic linkage in plants might enable rapid nuclear
      positioning in response to environmental stimuli.

PMID- 23973300
TI  - MicroRNA profiling and the role of microRNA-132 in neurodegeneration using a rat
      model.
AB  - MicroRNAs (miRs) are endogenous small RNAs that regulate gene expression at the
      post-transcriptional level by mediating mRNA degradation or transcriptional
      inhibition. MiRs were implicated in the pathogenesis of numerous
      neurodegenerative diseases, including Parkinson's disease (PD). In this study we
      analyzed the possible role of miRs in the neurodegenerative process in a
      spontaneous autosomal recessive rat model for neurodegeneration developed in our
      laboratory. To investigate the role of miRs in the etiology of PD, we conducted
      miR expression profiling using microarrays. We found 20 miRs that are deregulated
      in affected rats and many of these are implicated in neurodegenerative disease,
      including PD. In this study we were particularly interested in the expression of
      miR-132, a miR that has been reported to be highly expressed in neurons, and to
      have a potential role in neurodegenerative diseases. We found a significant
      increase in miR-132 in affected rats by microarray and the result was confirmed
      by qPCR. Next we analyzed one of the known downstream targets of miR-132, nuclear
      receptor related 1 protein (Nurr1), which is essential in neurogenesis of
      midbrain dopaminergic neurons. Western blot analysis and immunohistochemistry
      revealed a significant decrease in Nurr1 protein expression in the mesencephalic
      neurons. Finally, we found a significant decrease in both serum and mesencephalon
      brain tissue of brain-derived neurotrophic factor (BDNF), which is known to be a
      direct target of Nurr1. Taken together, our findings suggest that miR-132 can
      regulate Nurr1 levels and might influence the development and function of
      midbrain dopaminergic neurons. 

PMID- 23973299
TI  - A novel method to predict regulatory regions based on histone mark landscapes in
      macrophages.
AB  - Macrophages as phagocytes and professional antigen presenting cells play critical
      roles in both innate and adaptive immunity. Main transcription factors acting
      during their differentiation and function are known, but the behavior and co
      operation of these factors still remained unexplored. We introduce a new approach
      to map nucleosome-free regions using exclusively active enhancer and core
      promoter marking histone modification ChIP-seq data. We could detect
      approximately 56,000 potential active enhancers/promoters showing different
      lengths and histone modification shapes. Beside the highly enriched PU.1 and
      C/EBP sites, we could also detect binding sites for RUNX and AP-1, as well as for
      the MiT (MITF-TFE) family and MEF2 proteins. The PU.1 and C/EBP transcription
      factors are known for transforming cells into macrophages. The other
      transcription factors found in this study can play a role in macrophages as well,
      since it is known that the MiT family proteins are responsible for phagocytic
      activity and the MEF2 proteins specify monocytic differentiation over the
      granulocyte direction. Our results imply that this method can provide novel
      information about transcription factor organization at enhancers and core
      promoters as well as about the histone modifications surrounding regulatory
      regions in any immune or other cell types. 

PMID- 23973301
TI  - Protective effect of SIRT1 on toxicity of microglial-derived factors induced by
      LPS to PC12 cells via the p53-caspase-3-dependent apoptotic pathway.
AB  - Sirtuin1 (SIRT1) has protective effects in some neurodegenerative disease models,
      but it is not clear whether SIRT1 play the same role on inflammation-mediated
      Parkinson's disease (PD) models. In this study, we firstly established an
      inflammation environment by stimulating microglial BV-2 cells with the
      inflammatory agent lipopolysaccharides (LPS), which demonstrated by increasing of
      the levels of TNF-a, and IL-6 in cultured medium. Then we exposed PC12 cells (a
      model of catecholaminergic neuronal cells) with the supernant from LPS stimulated
      BV-2 cells (activated BV-2). PC12 cell apoptosis and SIRT1 involved protection
      were investigated. The results indicated that treatment with LPS caused
      significant decrease in SIRT1 expression in activated BV-2 cells, and increased
      the levels of TNF-a and IL-6, as measured by ELISA, whereas resveratrol (a known
      SIRT1 activator) suppressed this effect, which was conversely strengthened by
      sirtinol (a SIRT1 inhibitor), suggesting that SIRT1 may be involved in regulating
      proinflammatory cytokines from microglial activation. Further, we found that
      factors derived from activated microglia significantly decreased the level of
      deacetylation of p53 by reducing the expression of SIRT1, an effect that
      increased the apoptosis of PC12 and reduced cell viability. The addition of
      resveratrol could protect PC12 cells from inflammation-mediated damage above
      mentioned, while nicotinamide (another SIRT1 inhibitor) treatment had the
      opposite effect of resveratrol. Together, these data suggests that: SIRT1
      inhibits LPS-mediated proinflammatory cytokines release in microglia, and
      circumvents dopaminergic neurons injury induced by activated microglial-derived
      factors via p53-caspase-3-dependent mechanism of apoptosis. Thus, upregulation of
      SIRT1 provides a promising research field for therapeutic intervention in
      neuroinflammation diseases. 

PMID- 23973302
TI  - Analgesics as reinforcers with chronic pain: Evidence from operant studies.
AB  - Previously preclinical pain research has focused on simple behavioral endpoints
      to assess the efficacy of analgesics in acute and chronic pain models, primarily
      reflexive withdrawal from an applied mechanical or thermal stimulus. However
      recent research has been aimed at investigating other behavioral states in the
      presence of pain, including spontaneous, non-elicited pain. One approach is to
      investigate the reinforcing effects of analgesics in animals with experimental
      pain, which should serve as reinforcers by virtue of their ability to alleviate
      the relevant subjective states induced by pain. The gold standard for assessing
      drug reinforcement is generally accepted to be drug self-administration, and this
      review highlights the ability of drugs to serve as reinforcers in animals with
      experimental neuropathic pain, and the extent to which this behavior is altered
      in chronic pain states. Additionally, intracranial self-stimulation is an operant
      procedure that has been used extensively to study drug reinforcement mechanisms
      and the manner in which neuropathic pain alters the ability of drugs to serve as
      reinforcers in this paradigm will also be discussed. Drug self-administration and
      intracranial self-stimulation have promise as tools to investigate behavioral
      effects of analgesics in animals with chronic pain, particularly regarding the
      mechanisms through which these drugs motivate consumption in a chronic pain
      state.

PMID- 23973304
TI  - Spontaneous calcium waves in granule cells in cerebellar slice cultures.
AB  - Multiple regions in the CNS display propagating correlated activity during
      embryonic and postnatal development. This activity can be recorded as waves of
      increased calcium concentrations in spiking neurons or glia cells, and have been
      suggested to be involved in patterning, axonal guidance and establishment of
      synaptic transmission. Here, we used calcium imaging in slice cultures of the
      postnatal cerebellum, and observe spontaneous propagating calcium waves in NeuN
      positive granule-like cells. Wave formation was blocked by TTX and the AMPA
      antagonist NBQX, but persisted after NMDA receptor blockade with MK-801. Whole
      cell recordings during wave formation showed cyclic EPSP barrages with an
      amplitude of 10-20 mV concurrent with wave activity. Local non-propagating
      putative transglial waves were also present in the cultures, and could be
      reproduced by pressure application of ATP. We hypothesize, that the propagating
      wave activity is carried through the tissue by axonal collaterals formed by
      neighboring granule cells, and further suggest that the correlated activity may
      be related to processes that ensure correct postnatal wiring of the cerebellar
      circuits.

PMID- 23973303
TI  - Contribution of CA3 and CA1 pyramidal neurons to the tonic alpha7 nAChR-dependent
      glutamatergic input to CA1 pyramidal neurons.
AB  - The Schaffer collaterals are among the major glutamatergic inputs to CA1
      pyramidal neurons, the primary output of the hippocampus, which also receive
      sparse recurrent inputs from pyramidal neurons in the CA1 field. Although
      tonically active alpha7 nicotinic acetylcholine receptors (nAChRs) have been
      shown to sustain spontaneous glutamate transmission to CA1 pyramidal neurons in
      hippocampal slices under resting conditions, it remains to be determined whether
      these receptors are those expressed by CA3 or CA1 pyramidal neurons. This study
      was designed to test the hypothesis that the CA3 field of the hippocampus is a
      significant source of alpha7 nAChR-sustained glutamatergic transmission to CA1
      pyramidal neurons. To this end, spontaneous excitatory postsynaptic currents
      (EPSCs) were recorded from CA1 and CA3 pyramidal neurons in intact rat
      hippocampal slices as well as from CA1 pyramidal neurons in CA3-ablated slices
      under various experimental conditions. Surgical removal of the CA3 region from
      the slices reduced by 20% the frequency of spontaneous EPSCs recorded from CA1
      pyramidal neurons. This finding is in agreement with the concept that the CA3
      field contributes significantly to the maintenance of spontaneous glutamatergic
      synaptic activity in CA1 pyramidal neurons. In addition, the alpha7 nAChR
      antagonist methyllycaconitine (MLA, 10nM) reduced the frequency of spontaneous
      EPSCs recorded from CA1 pyramidal neurons by 30% in intact slices and 12% in CA3
      ablated slices. Taken together, these results demonstrate that tonically active
      alpha7 nAChRs in CA3 pyramidal neurons and/or in the Mossy fibers that innervate
      the CA3 pyramidal neurons do in fact contribute to the maintenance of
      glutamatergic synaptic activity in CA1 pyramidal neurons of hippocampal slices
      under resting conditions. 

PMID- 23973305
TI  - Sex-independent suppression of experimental inflammatory pain by minocycline in
      two mouse strains.
AB  - The research on sex differences in nociception and antinociception as well as sex
      and gender differences in pain and analgesia is a maturing field. There is a vast
      literature showing experimental and clinical pain suppressive effects induced by
      minocycline, especially in inflammatory pain. However, as far as we know,
      possible qualitative or quantitative sex differences in those effects remained to
      be examined. By employing the formalin test, which has two phases of experimental
      pain behavior that models nociceptive pain (i.e., first phase) and inflammatory
      pain (i.e., second phase), we initially evaluated the effect induced by
      minocycline in female or male C57BL/6 mice. The treatment reduced the second
      phase of licking behavior in both females and males, and the effects were
      quantitatively similar in both sexes. Likewise, the same sex-independent effect
      was observed in Swiss mice, suggesting a genotype-unspecific sex-independent
      effect. While minocycline is already being tested in clinical trials, this
      appears to be the first preclinical investigation of sex differences in the
      experimental pain suppressive effects induced by this widely studied drug. The
      independence of sex in the antinociceptive effect induced by minocycline may be
      hopefully translated to gender-independent analgesic effects, which would be
      surely promising in a therapeutic paradigm. 

PMID- 23973306
TI  - Nonlinear dynamical structure of sway path during standing in patients with
      multiple sclerosis and in healthy controls is affected by changes in sensory
      input and cognitive load.
AB  - Although several studies have applied traditional linear measures to evaluate
      postural control of patients with multiple sclerosis (MS), little is known about
      the nonlinear dynamics of this patient group. In this study, recurrence
      quantification analysis (RQA), a well documented nonlinear method, was used to
      compare the nonlinear dynamical structure of postural sway in two groups
      consisting of MS patients (n=23) and healthy matched controls (n=23). The study
      focuses on three levels of postural difficulty consisting of (1) standing on a
      rigid surface (force platform) with eyes open, (2) standing on a rigid surface
      with eyes closed, and (3) standing on a foam surface with eyes closed. The two
      levels of cognitive difficulty measured, consisted of a single postural task and
      a dual postural-cognitive task. It was observed that as the postural conditions
      became more difficult, the center of pressure (COP) time series of both groups
      became less regular as recorded in lower recurrence rate, less complex in
      deterministic structure as reflected in lower RQA entropy, and less nonstationary
      as reflected in the recording of lower Trend. Moreover, as cognitive conditions
      became more difficult, COP time series became less regular (lower %Rec in the
      anteroposterior direction and lower %Det in both directions), less complex in
      deterministic structure (lower RQA Ent in the anteroposterior direction), and
      less nonstationary (lower trend in the anteroposterior direction). The analytical
      results of the research show that there is a similar dynamical structure for both
      the MS patients and the control group; however, the nonlinear behavior of both
      groups was different under various experimental conditions. 

PMID- 23973307
TI  - Alterations of cortical excitability and central motor conduction time in
      Wilson's disease.
AB  - Wilson's disease (WD) leads to widespread structural alterations of central
      nervous system and our objectives were to determine the cortical excitability
      changes in WD by using transcranial magnetic stimulation (TMS). Thirteen patients
      with WD, diagnosed by the presence of Kayser-Fleischer ring and biochemical
      tests, were studied. TMS was performed using a figure-of-eight coil attached to
      Magstim 200 stimulator. Motor evoked potentials (MEP) were recorded from right
      first dorsal interosseous at rest. Resting motor threshold (RMT) was determined
      using standard techniques and central motor conduction time (CMCT) by 'F' wave
      method. Comparison was made with control data of our laboratory. Dysarthria was
      the presenting symptom in 5 patients (38.5%) and chorea, tremors, dystonia and
      abnormal gait in 2 patients each (15.4%). RMT was recordable in 10 patients and
      not recordable in 3. Compared to controls, patients in whom RMT was recordable,
      had significantly higher mean RMT (80.9 +/- 14.8 vs. 41.1 +/- 7, p<0.0001) and
      CMCT (6.7 +/- 0.5 ms vs. 4.8 +/- 0.6 ms; p<0.0001). In 2 of the 3 patients with
      non-recordable RMT, MEP could be obtained with active contraction. CMCT in these
      2 patients was also prolonged. Patients with WD have reduced cortical
      excitability and prolonged CMCT which may be due to the intracortical presynaptic
      motor dysfunction.

PMID- 23973308
TI  - Dual release of dexamethasone and TGF-beta3 from polymeric microspheres for stem
      cell matrix accumulation in a rat disc degeneration model.
AB  - Low back pain is frequently caused by nucleus pulposus (NP) degeneration. Tissue
      engineering is a powerful therapeutic strategy which could restore the normal
      biomechanical motion of the human spine. Previously we reported that a new
      nanostructured three-dimensional poly(lactide-co-glycolide) (PLGA) microsphere,
      which is loaded with dexamethasone and growth factor embedded heparin/poly(l
      lysine) nanoparticles via a layer-by-layer system, was an effective cell carrier
      in vitro for NP tissue engineering. This study aimed to investigate whether the
      implantation of adipose-derived stem cell (ADSC)-seeded PLGA microspheres into
      the rat intervertebral disc could regenerate the degenerated disc. Changes in
      disc height by plain radiograph, T2-weighted signal intensity in magnetic
      resonance imaging (MRI), histology, immunohistochemistry and matrix-associated
      gene expression were evaluated in normal controls (NCs) (without operations), a
      degeneration control (DC) group (with needle puncture, injected only with
      Dulbecco's modified Eagle's medium), a PLGA microspheres (PMs) treatment group
      (with needle puncture, PLGA microspheres only injection), and PLGA microspheres
      loaded with ADSCs treatment (PMA) group (with needle puncture, PLGA microspheres
      loaded with ADSC injection) for a 24-week period. The results showed that at 24
      weeks post-transplantation, the PM and PMA groups regained disc height values of
      ~63% and 76% and MRI signal intensities of ~47% and 76%, respectively, compared
      to the NC group. Biochemistry, immunohistochemistry and gene expression analysis
      also indicated the restoration of proteoglycan accumulation in the discs of the
      PM and PMA groups. However, there was almost no restoration of proteoglycan
      accumulation in the discs of the DC group compared with the PM and PMA groups.
      Taken together, these data suggest that ADSC-seeded PLGA microspheres could
      partly regenerate the degenerated disc in vivo after implantation into the rat
      degenerative intervertebral disc.

PMID- 23973309
TI  - Connexin 36, a key element in pancreatic beta cell function.
AB  - The prevalence of diabetes at a global scale has markedly increased during the
      last three decades. Diabetes is a chronic disease that includes a group of
      metabolic disorders, in which high serum glucose levels is a common factor.
      Insulin is the only hormone that decreases serum glucose levels. Therefore, it is
      relevant to deepen our understanding of cell mechanisms that regulate insulin
      production and release. Insulin is produced in pancreatic islet beta cells. They
      are excitable cells and most of them are electrically coupled through gap
      junction channels. Connexin 36 (Cx36) has been identified at junctional membranes
      of islet beta cells in both rodents and humans. Co-localization of Cx36 with
      Cx30.2 has been recently identified. Functional studies in Cx36 deficient mice
      have provided direct evidence that Cx36 gap junction channels are necessary for
      the synchronization of [Ca(2+)]i oscillations in islet beta cells. The latter
      allows for the generation of insulin pulses in a single perfused islet. Moreover,
      Cx36 deficient mice were found to have altered serum insulin pulse dynamics and
      to be glucose intolerant. In addition, Cx36 has been recently identified as an
      early gene that is specifically expressed in embryonic beta cells, whose
      transcript and protein are upregulated in unison with the main wave of beta cell
      differentiation. In conclusion, Cx36 is critical for endocrine pancreatic
      function and may represent a molecular target for future prevention and treatment
      of diabetes. This article is part of the Special Issue Section entitled 'Current
      Pharmacology of Gap Junction Channels and Hemichannels'. 

PMID- 23973310
TI  - Minoxidil sulfate induced the increase in blood-brain tumor barrier permeability
      through ROS/RhoA/PI3K/PKB signaling pathway.
AB  - Adenosine 5'-triphosphate-sensitive potassium channel (KATP channel) activator,
      minoxidil sulfate (MS), can selectively increase the permeability of the blood
      tumor barrier (BTB); however, the mechanism by which this occurs is still under
      investigation. Using a rat brain glioma (C6) model, we first examined the
      expression levels of occludin and claudin-5 at different time points after
      intracarotid infusion of MS (30 MUg/kg/min) by western blotting. Compared to MS
      treatment for 0 min group, the protein expression levels of occludin and claudin
      5 in brain tumor tissue of rats showed no changes within 1 h and began to
      decrease significantly after 2 h of MS infusion. Based on these findings, we then
      used an in vitro BTB model and selective inhibitors of diverse signaling pathways
      to investigate whether reactive oxygen species (ROS)/RhoA/PI3K/PKB pathway play a
      key role in the process of the increase of BTB permeability induced by MS. The
      inhibitor of ROS or RhoA or PI3K or PKB significantly attenuated the expression
      of tight junction (TJ) protein and the increase of the BTB permeability after 2 h
      of MS treatment. In addition, the significant increases in RhoA activity and PKB
      phosphorylation after MS administration were observed, which were partly
      inhibited by N-2-mercaptopropionyl glycine (MPG) or C3 exoenzyme or LY294002
      pretreatment. The present study indicates that the activation of signaling
      cascades involving ROS/RhoA/PI3K/PKB in BTB was required for the increase of BTB
      permeability induced by MS. Taken together, all of these results suggested that
      MS might increase BTB permeability in a time-dependent manner by down-regulating
      TJ protein expression and this effect could be related to ROS/RhoA/PI3K/PKB
      signal pathway. 

PMID- 23973311
TI  - Zonisamide regulates basal ganglia transmission via astroglial kynurenine
      pathway.
AB  - To clarify the anti-parkinsonian mechanisms of action of zonisamide (ZNS), we
      determined the effects of ZNS on tripartite synaptic transmission associated with
      kynurenine (KYN) pathway (KP) in cultured astrocytes, and transmission in both
      direct and indirect pathways of basal ganglia using microdialysis. Interactions
      between cytokines [interferon-gamma (IFNgamma) and tumor-necrosis factor-alpha
      (TNFalpha)] and ZNS on astroglial releases of KP metabolites, KYN, kynurenic-acid
      (KYNA), xanthurenic-acid (XTRA), cinnabarinic-acid (CNBA) and quinolinic-acid
      (QUNA), were determined by extreme liquid-chromatography with mass-spectrometry.
      Interaction among metabotropic glutamate-receptor (mGluR), KP metabolites and ZNS
      on striato-nigral, striato-pallidal GABAergic and subthalamo-nigral glutamatergic
      transmission was examined by microdialysis with extreme liquid-chromatography
      fluorescence resonance-energy transfer detection. Acute and chronic ZNS
      administration increased astroglial release of KYN, KYNA, XTRA and CNBA, but not
      QUNA. Chronic IFNgamma administration increased the release of KYN, KYNA, CNBA
      and QUNA, but had minimal inhibitory effect on XTRA release. Chronic TNFalpha
      administration increased CNBA and QUNA, but not KYN, KYNA or XTRA. ZNS inhibited
      IFNgamma-induced elevation of KYN, KYNA and QUNA, but enhanced IFNgamma-induced
      that of CNBA. TNFalpha-induced rises in CNBA and QUNA were inhibited by ZNS. ZNS
      inhibited striato-nigral GABAergic, striato-pallidal GABAergic and subthalamo
      nigral glutamatergic transmission via activation of groups II and III mGluRs. ZNS
      enhanced astroglial release of endogenous agonists of group II mGluR, XTRA and
      group III mGluR, CNBA. Activated endogenous mGluR agonists inhibited transmission
      in direct and indirect pathways of basal ganglia. These mechanisms contribute to
      effectiveness and well tolerability of ZNS as an adjunct treatment for
      Parkinson's disease during l-DOPA monotherapy. This article is part of the
      Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. 

PMID- 23973312
TI  - Chronic ceftriaxone treatment rescues hippocampal memory deficit in AQP4 knockout
      mice via activation of GLT-1.
AB  - Aquaporin-4 (AQP4) is the predominant water channel protein in the mammalian
      brain, and is mainly expressed in astrocytes. Besides its important role in water
      transport across the blood-brain barrier, our present study demonstrated that
      AQP4 deficiency impaired hippocampal long-term potentiation (LTP) and hippocampus
      dependent memory formation, accompanied by the increase in extracellular
      glutamate concentration and N-methyl-d-aspartate (NMDA) receptor-mediated
      currents in hippocampal dentate gyrus (DG) region. The impairment of LTP and
      memory formation of AQP4 knockout (KO) mice was mediated by the downregulation of
      glutamate transporter-1 (GLT-1) expression/function, since it can be rescued by
      beta-lactam antibiotic ceftriaxone (Cef), a potent GLT-1 stimulator. These
      results suggest that AQP4 functions as the modulator of synaptic plasticity and
      memory, and chronic Cef treatment rescues hippocampal memory deficit induced by
      AQP4 knockout. 

PMID- 23973313
TI  - Structure-based discovery of antagonists for GluN3-containing N-methyl-D
      aspartate receptors.
AB  - NMDA receptors are ligand-gated ion channels that assemble into tetrameric
      receptor complexes composed of glycine-binding GluN1 and GluN3 subunits (GluN3A
      B) and glutamate-binding GluN2 subunits (GluN2A-D). NMDA receptors can assemble
      as GluN1/N2 receptors and as GluN3-containing NMDA receptors, which are either
      glutamate/glycine-activated triheteromeric GluN1/N2/N3 receptors or glycine
      activated diheteromeric GluN1/N3 receptors. The glycine-binding GluN1 and GluN3
      subunits display strikingly different pharmacological selectivity profiles.
      However, the pharmacological characterization of GluN3-containing receptors has
      been hampered by the lack of methods and pharmacological tools to study GluN3
      subunit pharmacology in isolation. Here, we have developed a method to study the
      pharmacology of GluN3 subunits in recombinant diheteromeric GluN1/N3 receptors by
      mutating the orthosteric ligand-binding pocket in GluN1. This method is suitable
      for performing compound screening and characterization of structure-activity
      relationship studies on GluN3 ligands. We have performed a virtual screen of the
      orthosteric binding site of GluN3A in the search for antagonists with selectivity
      for GluN3 subunits. In the subsequent pharmacological evaluation of 99 selected
      compounds, we identified 6-hydroxy-[1,2,5]oxadiazolo[3,4-b]pyrazin-5(4H)-one
      (TK80) a novel competitive antagonist with preference for the GluN3B subunit.
      Serendipitously, we also identified [2-hydroxy-5-((4-(pyridin-3-yl)thiazol-2
      yl)amino]benzoic acid (TK13) and 4-(2,4-dichlorobenzoyl)-1H-pyrrole-2-carboxylic
      acid (TK30), two novel non-competitive GluN3 antagonists. These findings
      demonstrate that structural differences between the orthosteric binding site of
      GluN3 and GluN1 can be exploited to generate selective ligands. 

PMID- 23973316
TI  - Dysfunctional synapse in Alzheimer's disease - A focus on NMDA receptors.
AB  - Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly.
      Alterations capable of causing brain circuitry dysfunctions in AD may take
      several years to develop. Oligomeric amyloid-beta peptide (Abeta) plays a complex
      role in the molecular events that lead to progressive loss of function and
      eventually to neurodegeneration in this devastating disease. Moreover, N-methyl-D
      aspartate (NMDA) receptors (NMDARs) activation has been recently implicated in AD
      related synaptic dysfunction. Thus, in this review we focus on glutamatergic
      neurotransmission impairment and the changes in NMDAR regulation in AD, following
      the description on the role and location of NMDARs at pre- and post-synaptic
      sites under physiological conditions. In addition, considering that there is
      currently no effective ways to cure AD or stop its progression, we further
      discuss the relevance of NMDARs antagonists to prevent AD symptomatology. This
      review posits additional information on the role played by Abeta in AD and the
      importance of targeting the tripartite glutamatergic synapse in early
      asymptomatic and possible reversible stages of the disease through preventive
      and/or disease-modifying therapeutic strategies. This article is part of the
      Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.

PMID- 23973314
TI  - Low- and high-cocaine locomotor responding rats differ in reinstatement of
      cocaine seeking and striatal mGluR5 protein expression.
AB  - Behavioral responsiveness to initial cocaine use varies among individuals and may
      contribute to differential vulnerability to cocaine addiction. Rats also exhibit
      individual differences in cocaine's effects and can be classified as low or high
      cocaine responders (LCRs or HCRs, respectively), based on their initial cocaine
      induced locomotor activity (10 mg/kg, i.p.). Here, we used the
      extinction/reinstatement model to address whether or not LCRs and HCRs differ in
      (i) extinction/reinstatement of cocaine self-administration behavior and (ii)
      levels of metabotropic glutamate receptors (mGluRs) following these behaviors.
      During the earliest acquisition sessions, LCRs exhibited significantly greater
      cocaine intake (0.8 mg/kg/infusion) and cocaine-paired lever responding than
      HCRs, but intake and lever responding converged by the end of the cocaine self
      administration portion of the study. LCRs and HCRs did not differ in cocaine
      seeking during the first extinction session and extinguished cocaine seeking
      similarly. HCRs exhibited greater reinstatement than LCRs to lower (2.5 and 5
      mg/kg), but not higher (10 mg/kg), i.p. priming doses of cocaine. The effect of
      drug-paired cues on reinstatement following extinction was complex, with HCRs and
      LCRs showing the greater effect of cue depending on the order in which cue- and
      drug-primed tests were given. Western blot analysis revealed that mGluR5
      heteromers were significantly higher in the dorsal striatum of HCRs than LCRs
      following reinstatement testing. Although our previous findings with the LCR/HCR
      model have uniformly supported the idea that lower initial cocaine-induced
      activation predicts more ready development of cocaine addiction-like behaviors,
      here, we show a more complex relationship with cocaine reinstatement. 

PMID- 23973317
TI  - Phosphodiesterase 10A controls D1-mediated facilitation of GABA release from
      striato-nigral projections under normal and dopamine-depleted conditions.
AB  - In the present study, we found that PDE10A inhibitor papaverine, alone or in
      combination with the D1 receptor agonist SKF38393, did not change spontaneous
      IPSCs (sIPSCs) frequency or amplitude in the substantia nigra pars reticulata
      (SNpr). An increase in frequency, but not in amplitude, of sIPSCs was only
      observed when SKF38393 and PDE10A inhibitors were associated to perfusion with
      higher extracellular K(+). On the other hand, the amplitude of evoked IPSCs
      (eIPSCs) of the striato-nigral projection to SNpr, was increased in response to
      co-administration of SKF38393 and papaverine in normal extracellular potassium.
      Of note, both an increase in sIPSCs frequency and eIPSC amplitude could be
      obtained either by a robust stimulation of adenylyl cyclase (AC) with forskolin
      (10 MUM) or by a lower dose of forskolin (1 MUM) associated to PDE inhibition. We
      next investigated the effects produced by dopamine (DA) depletion in the
      striatum. Under this condition, SKF38393 alone increased either sIPSCs frequency
      and eIPSC amplitude. In addition, in the striatum of DA-depleted mice we found
      reduced PDE10A levels and higher cAMP-dependent phosphorylation in response to D1
      receptor stimulation. In accordance with these biochemical data, perfusion with
      papaverine had no effect on the SKF38393-induced changes of IPSCs in slices of DA
      depleted mice. These findings reveal a dynamic interplay between PDE10A activity,
      level of neuronal network depolarization and degree of dopaminergic tone in the
      ability of D1 receptors to facilitate the GABAergic transmission to SNpr neurons
      from the direct nigro-striatal pathway. This article is part of the Special Issue
      entitled 'The Synaptic Basis of Neurodegenerative Disorders'. 

PMID- 23973318
TI  - Selective inhibition of phosphodiesterase 10A impairs appetitive and aversive
      conditioning and incentive salience attribution.
AB  - The pharmacological effect of the selective PDE10A inhibitor 2-[4-(1-methyl-4
      pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline succinic acid (MP-10) on
      aversively and appetitively motivated behavior in C57BL/6J mice was examined. MP
      10 dose-dependently impaired performance on a highly demanding reward schedule
      during appetitive conditioning. The compound further affected cue-based, but not
      contextual aversive conditioning. Finally, dose-dependent impaired performance in
      an instrumentally conditioned reinforcement (ICR) task was found. This suggests
      that the observed behavioral effects of MP-10 can be at least partially ascribed
      to impaired incentive salience attribution. MP-10 administration dose-dependently
      enhanced striatal expression of the immediate early gene Zif268, which suggest
      that MP-10 affects the studied motivated behaviors by enhancing PDE10A-regulated
      striatal signaling. Striatal signaling thus appears to be crucial in processes
      that control reward-motivated behavior in general, and incentive salience
      attribution in particular. Continued research will prove valuable towards a
      better understanding of psychopathologies that affect reward-motivated behaviors,
      such as drug addiction and schizophrenia. 

PMID- 23973319
TI  - Schizophrenia as a self-disorder due to perceptual incoherence.
AB  - The aim of this review is to describe the potential relationship between
      multisensory disintegration and self-disorders in schizophrenia spectrum
      disorders. Sensory processing impairments affecting multisensory integration have
      been demonstrated in schizophrenia. From a developmental perspective multisensory
      integration is considered to be crucial for normal self-experience. An impairment
      of multisensory integration is called 'perceptual incoherence'. We theorize that
      perceptual incoherence may evoke incoherent self-experiences including
      depersonalization, ambivalence, diminished sense of agency, and 'loosening of
      associations' between thoughts, feelings and actions that lie within the
      framework of 'self-disorders' as described by Sass and Parnas (2003). We
      postulate that subconscious attempts to restore perceptual coherence may induce
      hallucinations and delusions. Increased insight into mechanisms underlying 'self
      disorders' may enhance our understanding of schizophrenia, improve recognition of
      early psychosis, and extend the range of therapeutic possibilities. 

PMID- 23973320
TI  - Executive functioning in schizophrenia: the result of impairments in lower order
      cognitive skills?
AB  - Executive functioning (EF) impairments are common in schizophrenia. There are two
      propositions regarding the causes of these impairments: (1) executive impairments
      are the result of the compounding effects of deficits in lower order cognitive
      skills (e.g. processing speed, attention) or (2) EF impairments exist in their
      own right regardless of lower order skills. It is difficult to examine the
      separable effects of lower order cognitive skills on EF given the overlap
      required to complete most neuropsychological measures. One battery designed to
      parcel out the contributions of lower order skills from EF is the Delis-Kaplan
      Executive Function System (D-KEFS). Inhibition and switching specifically were
      examined using the D-KEFS versions of the Stroop and Trails task. No group
      differences in task performance after controlling for lower level skills would
      provide evidence for a generalised cognitive deficit. Group differences remaining
      after controlling for these influences would suggest a disproportionate deficit.
      Results supported both propositions. On both tasks, group differences reflecting
      slowed reaction time in the schizophrenia group disappeared when lower order
      skills were controlled for. Differences between groups performance in errors were
      only evident on the most complex versions of each task with more errors made by
      the schizophrenia group. These results suggest that (1) both RT and error data
      are needed to provide a full picture of performance and (2) the relationship
      between lower order and EF is too complex to provide support for one or the other
      proposal.

PMID- 23973315
TI  - Dopamine D3 and 5-HT1B receptor dysregulation as a result of psychostimulant
      intake and forced abstinence: Implications for medications development.
AB  - Addiction to psychostimulants, including cocaine and amphetamine, is associated
      with dysregulation of dopamine and serotonin (5-HT) neurotransmitter systems.
      Neuroadaptations in these systems vary depending on the stage of the drug taking
      abstinence-relapse cycle. Consequently, the effects of potential treatments that
      target these systems may vary depending on whether they are given during
      abstinence or relapse. In this review, we discuss evidence that dopamine D3
      receptors (D3Rs) and 5-HT1B receptors (5-HT1BRs) are dysregulated in response to
      both chronic psychostimulant use and subsequent abstinence. We then review
      findings from preclinical self-administration models which support targeting D3Rs
      and 5-HT1BRs as potential medications for psychostimulant dependence. Potential
      side effects of the treatments are discussed and attention is given to studies
      reporting positive treatment outcomes that depend on: 1) whether testing occurs
      during self-administration versus abstinence, 2) whether escalation of drug self
      administration has occurred, 3) whether the treatments are given repeatedly, and
      4) whether social factors influence treatment outcomes. We conclude that D3/D2
      agonists may decrease psychostimulant intake; however, side effects of D3/D2R
      full agonists may limit their therapeutic potential, whereas D3/D2R partial
      agonists have fewer undesirable side effects. D3-selective antagonists may not
      reduce psychostimulant intake during relapse, but nonetheless, may decrease
      motivation for seeking psychostimulants with relatively few side-effects. 5-HT1BR
      agonists provide a striking example of treatment outcomes that are dependent on
      the stage of the addiction cycle. Specifically, these agonists initially increase
      cocaine's reinforcing effects during maintenance of self-administration, but
      after a period of abstinence they reduce psychostimulant seeking and the
      resumption of self-administration. In conclusion, we suggest that factors
      contributing to dysregulation of monoamine systems, including drug history,
      abstinence, and social context, should be considered when evaluating potential
      treatments to better model treatment effects in humans. This article is part of a
      Special Issue entitled 'NIDA 40th Anniversary Issue'.

PMID- 23973321
TI  - Safety of 13-valent pneumococcal conjugate vaccine in infants and children: meta
      analysis of 13 clinical trials in 9 countries.
AB  - BACKGROUND: Meta-analyses enable summarization and interpretation of data across
      clinical trials. When applied to safety data they allow for detection of rare
      events. Recently, a 13-valent pneumococcal conjugate vaccine (PCV13) was approved
      in multiple countries worldwide for routine immunization of infants and young
      children. This meta-analysis was conducted to identify potentially clinically
      important rare safety events associated with PCV13. OBJECTIVE: To summarize the
      safety of PCV13 compared with 7-valent pneumococcal conjugate vaccine (PCV7)
      administered to infants and toddlers. METHODS: A meta-analysis was performed of
      integrated safety data from 13 infant studies (PCV13 n=4729 and PCV7 n=2760)
      conducted in 9 North American, European, and Asian countries. Local reactions at
      the vaccine injection site and systemic events were collected for 4-7 days after
      each dose into electronic diaries. Adverse events (AEs) were collected after each
      vaccination. RESULTS: Overall, rates of local reactions after any dose of the
      infant series were similar between PCV13 and PCV7 groups: tenderness (46.7% vs
      44.8%, respectively); swelling (28.5% vs 26.9%); and redness (36.4% vs 33.9%).
      After the toddler dose, tenderness was significantly higher among PCV7 subjects
      than PCV13 subjects (54.4% vs 48.8%; P=0.005). Frequencies of fever (>=38 degrees
      C) were similar in both groups and mostly mild (<=39 degrees C); incidence of
      moderate fever (>39 degrees C to <=40 degrees C) with PCV13 was <=2.8% after any
      infant dose and 5.0% after the toddler dose, compared with <=2.6% and 7.3%,
      respectively, with PCV7. Fever >40 degrees C was uncommon in both groups.
      Frequencies of decreased appetite, irritability, and sleep disturbances were
      similar in both groups. AEs were the types of conditions and symptoms expected in
      infants and children, and clinically significant differences between vaccine
      groups were not observed. CONCLUSION: PCV13 has a favorable safety profile
      similar to that of PCV7, a vaccine for which there is >10 years clinical
      experience.

PMID- 23973322
TI  - Hsp70 vaccination-induced primary immune responses in efferent lymph of the
      draining lymph node.
AB  - Bovine paratuberculosis is a highly prevalent chronic infection of the small
      intestine in cattle, caused by Mycobacterium avium subspecies paratuberculosis
      (MAP). In earlier studies we showed the protective effect of Hsp70/DDA subunit
      vaccination against paratuberculosis. In the current study we set out to measure
      primary immune responses generated at the site of Hsp70 vaccination. Lymph vessel
      cannulation was performed to obtain efferent lymph from the prescapular lymph
      node draining the neck area where the vaccine was applied. Hsp70 vaccination
      induced a significant increase of CD21(+) B cells in efferent lymph, accounting
      for up to 40% of efferent cells post-vaccination. Proliferation (Ki67(+)) within
      the CD21(+) B cell and CD4(+) T cell populations peaked between day 3 and day 5
      post-vaccination. From day 7, Hsp70-specific antibody secreting cells (ASCs)
      could be detected in efferent lymph. Hsp70-specific antibodies, mainly of the
      IgG1 isotype, were also detected from this time point onwards. However, post
      vaccination IFN-gamma production in efferent lymph was non-sustained. In
      conclusion, Hsp70-vaccination induces only limited Th1 type immune responsiveness
      as reflected in efferent lymph draining the vaccination site. This is in line
      with our previous observations in peripheral blood. The main primary
      immunological outcome of the Hsp70/DDA subunit vaccination is B cell activation
      and abundant Hsp70-specific IgG1 production. This warrants the question whether
      Hsp70-specific antibodies contribute to the observed protective effect of Hsp70
      vaccination in calves. 

PMID- 23973323
TI  - Neutralizing antibodies associated with exposure factors to Orthopoxvirus in
      laboratory workers.
AB  - Extensive use of Vaccinia virus (VACV) in research has led to associated
      accidental human exposure in laboratories worldwide. In spite of the social and
      economic relevance of Bovine Vaccinia outbreaks in Brazil, national data
      concerning laboratory workers handling these infectious agents are relatively
      scarce. Therefore, a serological survey was conducted in a Brazilian laboratory
      to evaluate staff exposure to orthopoxviruses (OPVs). Information concerning
      direct work with OPVs, vaccination status and laboratory accidents was collected
      and correlated to serology results. This study presents an opportunity for
      discussion of routine procedures involving OPVs in laboratories and their
      intrinsic risks. Aspects of the live attenuated smallpox vaccine are also
      discussed. 

PMID- 23973324
TI  - Improving influenza virus backbones by including terminal regions of MDCK-adapted
      strains on hemagglutinin and neuraminidase gene segments.
AB  - Reverse genetics approaches can simplify and accelerate the process of vaccine
      manufacturing by combining the desired genome segments encoding the surface
      glycoproteins from influenza strains with genome segments (backbone segments)
      encoding internal and non-structural proteins from high-growth strains. We have
      developed three optimized high-growth backbones for use in producing vaccine seed
      viruses for group A influenza strains. Here we show that we can further enhance
      the productivity of our three optimized backbones by using chimeric hemagglutinin
      (HA) and neuraminidase (NA) genome segments containing terminal regions (non
      coding regions (NCRs) and coding regions for the signal peptide (SP),
      transmembrane domain (TMD), and cytoplasmic tail (CT)) from two MDCK-adapted high
      growth strains (PR8x and Hes) and the sequences encoding the ectodomains of the
      A/Brisbane/10/2010 (H1N1) HA and NA proteins. Viruses in which both the HA and NA
      genome segments had the high-growth terminal regions produced higher HA yields
      than viruses that contained one WT and one chimeric HA or NA genome segment.
      Studies on our best-performing backbone indicated that the increases in HA yield
      were also reflected in an increase in HA content in partially purified
      preparations. Our results show that the use of chimeric HA and NA segments with
      high-growth backbones is a viable strategy that could improve influenza vaccine
      manufacturing. Possible mechanisms for the enhancement of HA yield are discussed.

PMID- 23973325
TI  - The impact of the universal infant varicella immunization strategy on Canadian
      varicella-related hospitalization rates.
AB  - INTRODUCTION: Varicella vaccine was introduced to the infant immunization
      schedule in each province or territory between 2000 and 2007 as a result of the
      Canadian Immunization Strategy. The impact of vaccinating children against this
      disease is potentially far reaching, as immunization may also benefit those
      segments of the population not immunized. The objective of this paper is to
      examine the effects of varicella vaccine on related hospitalizations across the
      entire Canadian population. METHODS: This study is an ecological study using
      annual hospitalization rates in all ten provinces between 1990 and 2010. RESULTS:
      There were decreased varicella-related hospitalization rates for all ages across
      Canada following the introduction of varicella vaccination programs. The majority
      of changes in hospitalization rates were greater than 70% across all ages less
      than 40. Statistically significant declines in hospitalization were found for
      children aged 1-4 (ranges from 65 to 93%), and children less than 1 (ranges from
      48 to 100%). Adults aged 20-39 and 40-59 also experienced statistically
      significant declines (55-100%, and 39-76% respectively). CONCLUSION: Results
      suggest that decreased circulation of varicella appears to significantly
      contribute to declines in varicella-related hospitalizations for infants <1, as
      well as adults aged 20-39.

PMID- 23973326
TI  - Intra-pituitary relationship of follicle stimulating hormone and luteinizing
      hormone during pubertal development in Atlantic bluefin tuna (Thunnus thynnus).
AB  - As part of the endeavor aiming at the domestication of Atlantic bluefin tuna
      (BFT; Thunnus thynnus), first sexual maturity in captivity was studied by
      documenting its occurrence and by characterizing the key hormones of the
      reproductive axis: follicle stimulating hormone (FSH) and luteinizing hormone
      (LH). The full length sequence encoding for the related hormone beta-subunits,
      bftFSHbeta and bftLHbeta, were determined, revealing two bftFSHbeta mRNA
      variants, differing in their 5' untranslated region. A quantitative immuno-dot
      blot assay to measure pituitary FSH content in BFT was developed and validated
      enabling, for the first time in this species, data sets for both LH and FSH to be
      compared. The expression and accumulation patterns of LH in the pituitary showed
      a steady increase of this hormone, concomitant with fish age, reaching higher
      levels in adult females compared to males of the same age class. Conversely, the
      pituitary FSH levels were elevated only in 2Y and adult fish. The pituitary FSH
      to LH ratio was consistently higher (>1) in immature than in maturing or pubertal
      fish, resembling the situation in mammals. Nevertheless, the results suggest that
      a rise in the LH storage level above a minimum threshold may be an indicator of
      the onset of puberty in BFT females. The higher pituitary LH levels in adult
      females over males may further support this notion. In contrast three year-old
      (3Y) males were pubertal while cognate females were still immature. However, it
      is not yet clear whether the advanced puberty in the 3Y males was a general
      feature typifying wild BFT populations or was induced by the culture conditions.
      Future studies testing the effects of captivity and hormonal treatments on
      precocious maturity may allow for improved handling of this species in a
      controlled environment which would lead to more cost-efficient farming. 

PMID- 23973327
TI  - Chaperone Nap1 shields histone surfaces used in a nucleosome and can put H2A-H2B
      in an unconventional tetrameric form.
AB  - The histone H2A-H2B heterodimer is an integral component of the nucleosome. The
      cellular localization and deposition of H2A-H2B into chromatin is regulated by
      numerous factors, including histone chaperones such as nucleosome assembly
      protein 1 (Nap1). We use hydrogen-deuterium exchange coupled to mass spectrometry
      to characterize H2A-H2B and Nap1. Unexpectedly, we find that at low ionic
      strength, the alpha helices in H2A-H2B are frequently sampling partially
      disordered conformations and that binding to Nap1 reduces this conformational
      sampling. We identify the interaction surface between H2A-H2B and Nap1 and
      confirm its relevance both in vitro and in vivo. We show that two copies of H2A
      H2B bound to a Nap1 homodimer form a tetramer with contacts between H2B chains
      similar to those in the four-helix bundle structural motif. The organization of
      the complex reveals that Nap1 competes with histone-DNA and interhistone
      interactions observed in the nucleosome, thereby regulating the availability of
      histones for chromatin assembly. 

PMID- 23973328
TI  - PICH: a DNA translocase specially adapted for processing anaphase bridge DNA.
AB  - The Plk1-interacting checkpoint helicase (PICH) protein localizes to ultrafine
      anaphase bridges (UFBs) in mitosis alongside a complex of DNA repair proteins,
      including the Bloom's syndrome protein (BLM). However, very little is known about
      the function of PICH or how it is recruited to UFBs. Using a combination of
      microfluidics, fluorescence microscopy, and optical tweezers, we have defined the
      properties of PICH in an in vitro model of an anaphase bridge. We show that PICH
      binds with a remarkably high affinity to duplex DNA, resulting in ATP-dependent
      protein translocation and extension of the DNA. Most strikingly, the affinity of
      PICH for binding DNA increases with tension-induced DNA stretching, which mimics
      the effect of the mitotic spindle on a UFB. PICH binding also appears to diminish
      force-induced DNA melting. We propose a model in which PICH recognizes and
      stabilizes DNA under tension during anaphase, thereby facilitating the resolution
      of entangled sister chromatids. 

PMID- 23973329
TI  - TRAF4 promotes TGF-beta receptor signaling and drives breast cancer metastasis.
AB  - TGF-beta signaling is a therapeutic target in advanced cancers. We identified
      tumor necrosis factor receptor-associated factor 4 (TRAF4) as a key component
      mediating pro-oncogenic TGF-beta-induced SMAD and non-SMAD signaling. Upon TGF
      beta stimulation, TRAF4 is recruited to the active TGF-beta receptor complex,
      where it antagonizes E3 ligase SMURF2 and facilitates the recruitment of
      deubiquitinase USP15 to the TGF-beta type I receptor (TbetaRI). Both processes
      contribute to TbetaRI stabilization on the plasma membrane and thereby enhance
      TGF-beta signaling. In addition, the TGF-beta receptor-TRAF4 interaction triggers
      Lys 63-linked TRAF4 polyubiquitylation and subsequent activation of the TGF-beta
      activated kinase (TAK)1. TRAF4 is required for efficient TGF-beta-induced
      migration, epithelial-to-mesenchymal transition, and breast cancer metastasis.
      Elevated TRAF4 expression correlated with increased levels of phosphorylated
      SMAD2 and phosphorylated TAK1 as well as poor prognosis among breast cancer
      patients. Our results demonstrate that TRAF4 can regulate the TGF-beta pathway
      and is a key determinant in breast cancer pathogenesis. 

PMID- 23973330
TI  - CTLA-4 polymorphism and clinical outcome post allogeneic hematopoietic stem cell
      transplantation.
AB  - CTLA-4 inhibitory molecule plays an important role in regulating T cell
      activation. It is considered a crucial element in keeping the immune balance and
      has been implicated in cancer, autoimmunity and transplantation immunology.
      Inconsistent observations are reported regarding its association with
      hematopoietic stem cell transplantation (HSCT). Genotyping of CTLA-4 was
      performed in recipients and their HLA-matched donors for +49A/G and CT60
      polymorphisms (80 and 94 pairs, respectively) using PCR-RFLP. No association was
      encountered between both polymorphisms in patients and donors and acute or
      chronic graft versus host disease. Significant association was observed between
      recipient +49A/G G allele and lower disease-free survival and overall survival
      compared to AA genotype (HR: 2.17, p = 0.03, 95% CI: 1.05-4.48 and HR: 2.54, p =
      0.01, 95% CI: 1.16-5.54), respectively. Our results suggest that CTLA-4
      genotyping may predict outcome in patients post HSCT. To validate our results,
      further studies on a larger cohort are needed.

PMID- 23973331
TI  - Role of endothelial cell metabolism in vessel sprouting.
AB  - Endothelial cells (ECs) are quiescent for years but can plastically switch to
      angiogenesis. Vascular sprouting relies on the coordinated activity of migrating
      tip cells at the forefront and proliferating stalk cells that elongate the
      sprout. Past studies have identified genetic signals that control vascular
      branching. Prominent are VEGF, activating tip cells, and Notch, which stimulates
      stalk cells. After the branch is formed and perfused, ECs become quiescent
      phalanx cells. Now, emerging evidence has accumulated indicating that ECs not
      only adapt their metabolism when switching from quiescence to sprouting but also
      that metabolism regulates vascular sprouting in parallel to the control by
      genetic signals. 

PMID- 23973332
TI  - A Central role for mTOR in lipid homeostasis.
AB  - The mechanistic target of rapamycin (mTOR) signaling pathway regulates many
      fundamental metabolic and physiological processes, including lipid metabolism. We
      explore recent findings on the role of mTOR in lipid homeostasis, with an
      emphasis on recent findings from in vivo models regarding the role of mTORC2 in
      lipolysis, lipogenesis, and adipogenesis. 

PMID- 23973333
TI  - Tear levels of tumor necrosis factor-alpha in patients with Parkinson's disease.
AB  - Neuroinflammatory events mediated by the pro-inflammatory cytokine tumor necrosis
      factor-alpha (TNF-alpha) cause progressive neurodegeneration in dopaminergic
      neurons, and play an important role in the pathogenesis of Parkinson's disease
      (PD). The purpose of this study was to determine TNF-alpha levels in tear samples
      obtained from patients with PD and to analyze the relationship between TNF-alpha
      values and PD characteristics. Eighteen patients with PD and 17 healthy control
      subjects were included in the study. We examined the patient demographics,
      modified Hoehn and Yahr Staging Scale (mHY) stages, Unified Parkinson's disease
      rating scale (UPDRS) II and III scores, Mini Mental State Examination (MMSE)
      scores, and the predominant symptoms. We measured TNF-alpha using the multiplex
      immunobead assay in unstimulated tear samples, and determined the Schirmer's test
      and blink rate for each subject. Tear TNF-alpha values were significantly higher
      in patients with PD (196.9 +/- 121.2 pg/ml) than in control subjects (110.7 +/-
      87.2 pg/ml; p=0.02). We identified no relationship between tear TNF-alpha levels
      and age, sex, age at onset, PD duration, mHY stages, UPDRS II, UPDRS III, or MMSE
      scores. The higher TNF-alpha levels observed in the tears of patients with PD
      suggests neuroinflammation and TNF-alpha plays a role in the pathogenesis of PD.
      Tear TNF-alpha levels, however, were not related to the duration or severity of
      PD. Tears are a suitable method for measuring TNF-alpha levels, and can be used
      as a diagnostic measure to evaluate biomarkers in PD.

PMID- 23973334
TI  - Classification of functional near-infrared spectroscopy signals corresponding to
      the right- and left-wrist motor imagery for development of a brain-computer
      interface.
AB  - This paper presents a study on functional near-infrared spectroscopy (fNIRS)
      indicating that the hemodynamic responses of the right- and left-wrist motor
      imageries have distinct patterns that can be classified using a linear classifier
      for the purpose of developing a brain-computer interface (BCI). Ten healthy
      participants were instructed to imagine kinesthetically the right- or left-wrist
      flexion indicated on a computer screen. Signals from the right and left primary
      motor cortices were acquired simultaneously using a multi-channel continuous-wave
      fNIRS system. Using two distinct features (the mean and the slope of change in
      the oxygenated hemoglobin concentration), the linear discriminant analysis
      classifier was used to classify the right- and left-wrist motor imageries
      resulting in average classification accuracies of 73.35% and 83.0%, respectively,
      during the 10s task period. Moreover, when the analysis time was confined to the
      2-7s span within the overall 10s task period, the average classification
      accuracies were improved to 77.56% and 87.28%, respectively. These results
      demonstrate the feasibility of an fNIRS-based BCI and the enhanced performance of
      the classifier by removing the initial 2s span and/or the time span after the
      peak value. 

PMID- 23973335
TI  - Would right atrial stretch inhibit sodium intake following GABAA receptor
      activation in the lateral parabrachial nucleus?
AB  - The knowledge of the mechanisms underlying circulating volume control may be
      achieved by stretching a balloon placed at the junction of the superior vena cava
      right atrial junction (SVC-RAJ). We investigated whether the inflation of a
      balloon at the SVC-RAJ inhibits the intake of 0.3M NaCl induced by GABAA receptor
      activation in the lateral parabrachial nucleus (LPBN) in euhydrated and satiated
      rats. Male Wistar rats (280-300 g) with bilateral stainless steel LPBN cannulae
      and balloons implanted at the SVC-RAJ were used. Bilateral injections of the
      GABAA receptor agonist muscimol (0.5 etamol/0.2l) in the LPBN with deflated
      balloons increased intake of 0.3M NaCl (30.1 +/- 3.9 vs. saline: 2.2 +/-
      0.7)ml/210 min, n=8) and water (17.7 +/- 1.9 vs. saline: 2.9 +/- 0.5 ml/210 min).
      Conversely, 0.3M NaCl (27.8 +/- 2.1 ml/210 min) and water (22.8 +/- 2.3 ml/210
      min) intake were not affected in rats with inflated balloons at the SVC-RAJ. The
      results show that sodium and water intake induced by muscimol injected into the
      LPBN was not affected by balloon inflation at the SVC-RAJ. We suggest that the
      blockade of LPBN neuronal activity with muscimol injections impairs inhibitory
      mechanisms activated by signals from cardiopulmonary volume receptors determined
      by balloon inflation.

PMID- 23973336
TI  - Do patients who experience episodic tilting or translational sensations in the
      pitch plane have abnormal sacculo-collic reflexes?
AB  - The otolith-collic and otolith-ocular reflexes of patients who experienced
      episodic tilting or translational sensations in the pitch plane without any other
      vestibular symptoms were assessed using cervical vestibular evoked myogenic
      potentials (cVEMP) and ocular vestibular evoked myogenic potentials (oVEMP).
      Eleven patients (4 men and 7 women, mean age=40.4) were enrolled. All of the
      patients complained of episodic tilting or translational sensations in the pitch
      plane. Patients with a medical history of rotatory vertigo, loss of
      consciousness, head trauma, or symptoms of central nervous dysfunction or
      proprioceptive dysfunction and those who had been definitely diagnosed with a
      disease that causes disequilibrium were excluded. All 11 patients underwent cVEMP
      and caloric tests. Ten patients participated in the oVEMP tests. Seven of the 11
      patients exhibited unilateral cVEMP absences, two displayed bilateral cVEMP
      absences, one demonstrated unilaterally decreased cVEMP, and one displayed normal
      cVEMP. Concerning oVEMP, 2 of the 10 patients showed unilateral oVEMP absences, 2
      displayed bilateral oVEMP absences, 2 exhibited unilaterally decreased oVEMP, and
      4 displayed normal oVEMP. All patients exhibited normal bilateral caloric
      responses. These findings were distinct from the results obtained for patients
      who experienced episodic lateral tilting sensations in previous studies. While
      most of the latter patients exhibited abnormal oVEMP, the patients in the present
      study tended to display abnormal cVEMP. These results suggest that patients with
      episodic tilting or translational sensations in the pitch plane suffer from
      saccular dysfunction. We propose "idiopathic otolithic vertigo" as a clinical
      entity and suggest that it is caused by idiopathic saccular dysfunction and/or
      utricular dysfunction. 

PMID- 23973337
TI  - Heterologous expression and purification of biologically active domains 3 and 4
      of human polymeric immunoglobulin receptor and its interaction with choline
      binding protein A of Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae, one of the common causes of pneumonia, colonises the
      epithelium via the interaction between a choline binding protein of S. pneumoniae
      and the human polymeric immunoglobulin receptor (pIgR). One of the functions of
      pIgR is to mediate the transcytosis of polymeric immunoglobulins from the
      basolateral to the apical surface of epithelial cells. S. pneumoniae invades
      human epithelial cells by exploiting the transcytosis machinery. Due to an
      increase in the prevalence of antibiotic resistant strains of S. pneumoniae, and
      the limitations and expense of the vaccines available, extensive research may
      provide insights into the potential of new therapeutic regimes. This study
      investigated the potential of pIgR domains as an alternative non-antibiotic
      immune therapy for treating pneumonia. The aim was to determine the binding
      affinity of recombinant D3D4 protein, the domains of pIgR responsible for binding
      S. pneumoniae, to recombinant R1R2 repeat domains of choline binding protein A of
      S. pneumoniae. Biologically active recombinant D3D4 was produced in Escherichia
      coli using a gel filtration chromatography refolding method, a novel approach for
      the refolding of pIgR domains, after the purification of inclusion bodies using
      nickel affinity chromatography. Surface Plasmon resonance (SPR) spectroscopy
      showed that purified recombinant D3D4 binds recombinant R1R2 with an equilibrium
      dissociation constant (KD) of 3.36*10(-7)M. 

PMID- 23973338
TI  - Novel therapeutic strategies for treatment of visceral leishmaniasis.
AB  - Leishmaniasis reveals itself in two forms, cutaneous and visceral, but the later
      exerts serious complications and may lead to death, if untreated. The
      availability of limited number of antileishmanial chemotherapeutic agents, the
      high cost of treatment, growing incidences of resistance to first line drugs as
      well as severe toxicities associated with the drugs complicate the treatment of
      visceral leishmaniasis. To overcome these problems, critical investigation of new
      therapeutic strategies with potential antileishmanial activity and good
      tolerability are essential. In this review we explore the different facets of
      novel therapeutic strategies for treatment of visceral leishmaniasis with a
      purpose to summarize all the possible treatment tactics, which will help
      scientists working in this arena to implement their research in a systematic
      manner. 

PMID- 23973339
TI  - Bearing arms against osteoarthritis and sarcopenia: when cartilage and skeletal
      muscle find common interest in talking together.
AB  - Osteoarthritis, a disease characterized by cartilage degradation, abnormal
      subchondral bone remodelling and some grade of inflammation, and sarcopenia, a
      condition of pathological muscle weakness associated with altered muscle mass,
      strength, and function, are prevalent disorders in elderly people. There is
      increasing evidence that decline in lower limb muscle strength is associated with
      knee or hip osteoarthritis in a context of pain, altered joint stability,
      maladapted postures and defective neuromuscular communication. At the cellular
      and molecular levels, chondrocytes and myoblasts share common pathological
      targets and pathways, and the close anatomical location of both cell types
      suggest a possibility of paracrine communication. In this review, we examine the
      relationship between osteoarthritis and sarcopenia in the musculoskeletal field,
      and discuss the potential advantage of concomitant therapies, or how each
      disorder may benefit from treatment of the other. 

PMID- 23973341
TI  - Introduction: Addressing the challenge of group B streptococcal disease.

PMID- 23973340
TI  - Driving external chemistry optimization via operations management principles.
AB  - Confronted with the need to significantly raise the productivity of remotely
      located chemistry CROs Pfizer embraced a commitment to continuous improvement
      which leveraged the tools from both Lean Six Sigma and queue management theory to
      deliver positive measurable outcomes. During 2012 cycle times were reduced by 48%
      by optimization of the work in progress and conducting a detailed workflow
      analysis to identify and address pinch points. Compound flow was increased by 29%
      by optimizing the request process and de-risking the chemistry. Underpinning both
      achievements was the development of close working relationships and productive
      communications between Pfizer and CRO chemists. 

PMID- 23973342
TI  - A maternal vaccine against group B Streptococcus: past, present, and future.
AB  - Group B Streptococcus (GBS) is a major cause of morbidity and mortality among
      neonates. Though there have been tremendous advances in prevention of invasive
      neonatal GBS disease through prophylactic antibiotic treatment of pregnant women,
      the incidence of neonatal disease has not changed significantly over the past
      several years. Vaccination of pregnant women is an important strategy that has
      the potential to improve further on existing protocols. In this review, we
      explore the history of the design of maternal GBS vaccines. We also discuss how
      recent applications of genomics and immunology to vaccine design promise to
      further enhance our ability to develop more effective vaccines against this
      important disease. 

PMID- 23973343
TI  - Assessments of vaccines for prenatal immunization.
AB  - The strategy of prenatal maternal immunization to protect the pregnant woman and
      her infant was first used with tetanus toxoid, when it was recognized that young
      infants had very high rates of tetanus disease, well before the age when infant
      immunizations are provided. Antenatal immunization has now been recommended and
      utilized for additional vaccines to prevent infections in pregnancy and the young
      infant. There are several issues to consider which are unique to the strategy of
      antenatal immunization. The first is that immunization of the pregnant woman will
      affect the woman who receives the vaccine, her developing fetus, and the young
      infant for several months after delivery. For this discussion, we will consider
      the availability of data for the maternal-fetal-infant triad in 4 aspects: This
      discussion will review available data from vaccines for prevention of tetanus,
      pneumococcal, influenza and pertussis infections used in antenatal maternal
      immunization programs. 

PMID- 23973344
TI  - The spectrum of perinatal group B streptococcal disease.
AB  - The progressive unfolding, over four decades, of an understanding of group B
      Streptococcus (GBS) and its global disease burden support the rationale for
      maternal immunization as a key strategy to prevent GBS perinatal infections. This
      review highlights, in historical context, the recognition of GBS as a human
      pathogen, definition of epidemiologic features of disease, pathogenesis,
      outcomes, impact of intrapartum antibiotic prophylaxis, development of
      glycoconjugate vaccines and appreciation of the global scope of GBS perinatal
      disease. These cumulative advances in the GBS field coupled with an increasing
      acceptance of immunization during pregnancy suggest the timing is optimal for
      introduction of a glycoconjugate GBS vaccine for use in pregnant women. 

PMID- 23973345
TI  - Group B streptococcal epidemiology and vaccine needs in developed countries.
AB  - Development of a group B streptococcal vaccine (GBS) vaccine is the most
      promising approach for the prevention of GBS infections in babies, given the
      potential adverse effects of intrapartum antibiotic prophylaxis as well as the
      need for effective prevention of both adult and late perinatal disease. There are
      numerous prevention strategies at this time but none are 100% effective in the
      eradication of neonatal early onset GBS disease and there are no preventative
      strategies for late onset disease. The need for a GBS vaccine is therefore, of
      utmost importance. Efforts applying genomics to GBS vaccine development have led
      to the identification of novel vaccine candidates. The publication of GBS whole
      genomes coupled with new technologies including multigenome screening and
      bioinformatics has also allowed researchers to overcome the serotype limitation
      of earlier vaccine preparations in the search of a universal effective vaccine
      against GBS. This review brings together the key arguments concerning the
      potential need of a GBS vaccine in developed countries and describes the current
      status with GBS epidemiology and microbiology in these countries. 

PMID- 23973346
TI  - Epidemiology of Group B Streptococcus in developing countries.
AB  - Group B Streptococcus (GBS) causes pneumonia, meningitis and sepsis in neonates.
      The current distribution pattern of GBS serotypes in developing countries such as
      India, China and Brazil is not clear. In order to appropriately plan for
      vaccination programs to address the burden of this disease in these countries,
      prospective population based studies are urgently needed. In our discussions, we
      focused on India, China and Brazil because of the membership of our workgroup,
      but data on other countries are also presented here. Further studies in
      developing countries are needed so as to better formulate appropriate public
      health interventions. 

PMID- 23973348
TI  - GBS public awareness, advocacy, and prevention--what's working, what's not and
      why we need a maternal GBS vaccine.
AB  - Group B Streptococcus (GBS) is the most common cause of severe early-onset (0-6
      days) infection and a significant cause of serious late-onset (7-90 days)
      infection in infants. While most babies recover from their GBS infection, some
      are stillborn, more die in the first weeks of life and others suffer lifelong
      disability. Despite efforts in many developed countries to prevent these
      infections, the burden of GBS disease remains significant, particularly among the
      late onset infections, which are not preventable using current risk-based or
      screening strategies. Vaccination, once available, could prevent more cases of
      GBS infection than any other strategy, including preventing preterm labor and
      stillbirths caused by GBS infection, post-delivery GBS infection in the mother
      and late-onset GBS infection in the baby. Vaccination would also avoid allergic
      reactions to antibiotics and concern about the emergence of antibiotic resistant
      bacteria. We consider the history of the two largest group B Strep parent
      organizations (Group B Strep Association USA and Group B Strep Support UK) and
      the history of GBS prevention in their respective countries. We look at what is
      needed before a vaccine can be introduced and consider how acceptable a GBS
      vaccine would be from families' perspective. We also summarize what a perfect GBS
      vaccine would look like and what we should all strive to achieve. 

PMID- 23973347
TI  - Considerations for a phase-III trial to evaluate a group B Streptococcus
      polysaccharide-protein conjugate vaccine in pregnant women for the prevention of
      early- and late-onset invasive disease in young-infants.
AB  - In 2010, an estimated 393,000 infection-related neonatal deaths occurred
      worldwide with Group B streptococcus (GBS) being a leading cause. Prevention of
      early-onset disease (0-6 days; EOD) is currently focused on intra-partum
      antibiotic prophylaxis to mothers identified as being at risk; such strategies
      reduce EOD by 75-80% but are resource-intensive and logistically-difficult to
      implement in developing countries. Vaccination of pregnant women is an alternate
      strategy for preventing both EOD and late-onset disease (7-89 days; LOD). A
      trivalent GBS polysaccharide-protein conjugate vaccine (GBS-CV) composed of
      capsular epitopes from serotypes Ia, Ib and III is undergoing phase-II evaluation
      among pregnant women in Europe, North America and Africa. These serotypes cause
      70-80% of all invasive GBS disease in early-infancy. Maternal anti-GBS antibodies
      are associated with protection from EOD, however, since a correlate of efficacy
      has not been defined, a phase III efficacy trial may be required for licensure.
      Criteria for selecting appropriate sites include sufficiently high GBS incidence
      in large birth cohorts, as well as adequate clinical and microbiological
      diagnostic skills and capacities. Alternate pathways to licensure should be
      explored, e.g. identification of serological correlates of protection with
      subsequent phase IV studies establishing vaccine-effectiveness against invasive
      GBS disease. Conducting a randomized, placebo-controlled efficacy trial, however,
      has the additional advantage of also being able to evaluate the role of GBS
      contributing to neonatal culture-negative sepsis, stillbirths, prematurity and
      low-birth weight. 

PMID- 23973349
TI  - An overview of global GBS epidemiology.
AB  - Streptococcus agalactiae (group B streptococcus (GBS)), remains the leading cause
      of neonatal sepsis and meningitis in many countries and an important cause of
      disease in pregnant women, immunocompromised adults and the elderly. Intrapartum
      antibiotic strategies have reduced the incidence of early-onset neonatal GBS
      where applied, but have had no impact on late onset GBS infection and only a
      limited impact on disease in pregnant women. In low/middle income settings, the
      disease burden remains uncertain although in several countries of Southern Africa
      appears comparable to that of high-income countries. Disease may be rapidly
      fulminating and cases therefore missed before appropriate samples are obtained.
      This may lead to significant underestimation of the true burden and be a
      particular issue in many African and Asian countries; comprehensive
      epidemiological data from such countries are urgently required. The available
      data suggest that the serotype distribution of GBS isolates is similar in Africa,
      Western Pacific, Europe, the Americas and the Eastern Mediterranean regions and
      has not changed over the past 30 years. Five serotypes (Ia, Ib, II, III, V)
      account for the majority of disease; conjugate vaccines including some or all of
      these serotypes therefore hold great promise for preventing this important
      disease. 

PMID- 23973350
TI  - Prospective comparison of the detection rates of human enterovirus and
      parechovirus RT-qPCR and viral culture in different pediatric specimens.
AB  - BACKGROUND: Reverse-transcriptase quantitative real-time polymerase chain
      reaction (RT-qPCR) has become the gold standard for the diagnosis of human
      enterovirus (EV) and parechovirus (HPeV) infections. The detection rate of RT
      qPCR in different pediatric body specimens has not been compared prospectively in
      a multicentre study. OBJECTIVES: This study compared the diagnostic detection
      rates of EV and HPeV RT-qPCR and viral culture in different specimens (feces,
      nasopharynx, blood, urine and cerebrospinal fluid (CSF)) of pediatric patients.
      STUDY DESIGN: This prospective, multicenter study performed an EV and HPeV RT
      qPCR on nasopharynx, blood, urine, feces and CSF specimens and a viral culture on
      nasopharynx, feces and CSF specimens in symptomatic children<16 years. RESULTS:
      Of 285 included children EV was detected in 140 (49%) and HPeV in 44 (15%)
      children. Both EV and HPeV RT-qPCR had a higher sensitivity and negative
      predictive value than EV and HPeV viral culture, respectively. EV and HPeV RT
      qPCR in feces specimen had the highest sensitivity (99.2% and 95.1%) of all
      specimens. Pooling results of specimens increased the detection rate for both
      viruses. CONCLUSION: Of all specimens, RT-qPCR in feces had the highest detection
      rate for both EV and HPeV in symptomatic pediatric patients. An EV was detected
      in all EV positive patients if a RT-qPCR was performed on both feces and CSF
      specimens or in both feces and urine specimens. HPeV was detected in all HPeV
      positive patients if a RT-qPCR was performed on both feces and CSF specimens,
      feces and nasopharynx specimens or CSF and nasopharynx specimens.

PMID- 23973351
TI  - Differences and commonalities in the judgment of causality in physical and social
      contexts: an fMRI study.
AB  - Understanding cause and effect is a fundamental aspect of human cognition. When
      shown videos of simple two-dimensional shapes colliding, humans experience one
      object causing the other to move, e.g., one billiard-like ball seeming to hit and
      move the other. The impression of causality can also occur when people attribute
      social interactions to moving objects. Whether the judgment of social and
      physical causality engages distinct or shared neural networks is not known. In a
      functional magnetic imaging (fMRI) study, participants were presented with two
      types of dynamic videos: a blue ball colliding with a red ball (P; physical
      condition) and a blue ball ("Mr. Blue") passing a red ball ("Mrs. Red") without
      making contact (S; social condition). Participants judged causal relationships
      (C) or movement direction (D; control task) in both video types, resulting in
      four conditions (PC; SC; PD; SD). We found common neural activations for physical
      and social causality judgments (SC > SD)?(PC > PD) in the right middle/inferior
      frontal gyrus, right inferior parietal lobule, the right supplementary motor
      area, and bilateral insulae. For social causal judgments (SC > PC), we found
      distinct neural activity in the right temporo-parietal junction (rTPJ). These
      results provide evidence for a common neural network underlying judgments of
      causality that apply to both physical and social situations. The results also
      indicate that social causality judgments recruit additional neural resources in
      an area critical for determining animacy and intentionality.

PMID- 23973352
TI  - Kinematic variability of the head, lumbar spine and knee during the "walk and
      turn to sit down" task in older and young adults.
AB  - This study investigates the kinematic variability of the head, lumbar spine and
      knee during the various walk and turn to sit phases in older and young adults.
      Sixteen older adults and eighteen young adults were recruited for this study.
      Each subject performed the "Walk and turn to sit down" test. A 16-channel
      telemetry system with electrogoniometers and an inclinometer was used to record
      the kinematic data. The turning step was divided into braking, mid-stance, swing
      and terminal load phases for kinematic analysis. The results showed that the
      older adults had a lower displacement angle and velocity of the lumbar spine,
      head and knee during different turning phases than the young adults. However,
      older adults performed turning with a higher variability in angular velocity of
      head flexion than the young adults during the turning step. The onset of lumbar
      movement and lateral flexion of the head occurred significantly earlier in older
      adults than in the young adults during turning. CONCLUSION: Older adults more
      cautiously control their motion by changing their trunk movement amplitude,
      velocity and timing in relation to their lower extremity movements during
      turning. The larger variability in angular velocity of head flexion may imply
      that older adults cannot precisely estimate the required movement for smooth
      turning.

PMID- 23973353
TI  - Plantar pressures in children with congenital talipes equino varus--a comparison
      between surgical management and the Ponseti technique.
AB  - The Ponseti technique for treatment for Congenital Talipes Equinovarus (CTEV) was
      introduced in the authors' institution in 2001, substituting a more traditional
      orthopaedic approach which involved surgery. There is currently limited published
      information regarding the differences in clinical outcomes between these two
      techniques, particularly in relation to plantar pressure analysis. This study
      aims to determine differences in pedobarographic outcome in children with CTEV,
      treated with either a surgical or Ponseti approach. A high resolution
      pedobarograph was used to record plantar pressure distribution in 52 children
      with CTEV and 26 children with typical development. Data were imported into
      Matlab where a custom programme was developed for processing and analysing
      pedobarographic recordings. There were significant differences in both treatment
      groups compared to the typically developed group (p<0.05) for most measurements.
      The most salient differences between treatment groups were (i) at the hind-foot
      where the Ponseti group had significantly lower maximum peak pressures (p<0.05);
      (ii) at the lateral mid-foot where children treated by the Ponseti approach
      showed significantly larger peak force (p<0.001), average peak pressure (p<0.001)
      and maximum peak pressure (p<0.01); (iii) at the lateral fore-foot where the
      surgical group showed lower average peak pressure (p<0.05); and (iv) in the
      medial/lateral fore-foot ratio where the Ponseti group showed significantly lower
      values (p<0.05). Plantar pressure analysis is a complementary measurement for the
      assessment of gait in children with CTEV. Data presented in this study showed
      that while there were deviations in children with CTEV, the differences observed
      between treatment groups suggest children in the Ponseti group have some level of
      under correction or recurrence.

PMID- 23973354
TI  - Comparative analysis of speed's impact on muscle demands during partial body
      weight support motor-assisted elliptical training.
AB  - Individuals with walking limitations often experience challenges engaging in
      functionally relevant exercise. An adapted elliptical trainer (motor to assist
      pedal movement, integrated body weight harness, ramps/stairs, and grab rails) has
      been developed to help individuals with physical disabilities and chronic
      conditions regain/retain walking capacity and fitness. However, limited published
      studies are available to guide therapeutic interventions. This repeated measures
      study examined the influence of motor-assisted elliptical training speed on lower
      extremity muscle demands at four body weight support (BWS) levels commonly used
      therapeutically for walking. Electromyography (EMG) and pedal trajectory data
      were recorded as ten individuals without known disability used the motor-assisted
      elliptical trainer at three speeds [20,40, 60 revolutions per minute (RPM)]
      during each BWS level (0%, 20%, 40%, 60%). Overall, the EMG activity (peak, mean,
      duration) in key stabilizer muscles (i.e., gluteus medius, gluteus maximus,
      vastus lateralis, medial gastrocnemius and soleus) recorded at 60 RPM exceeded
      those at 40 RPM, which were higher than values at 20 RPM in all but three
      situations (gluteus medius mean at 0% BWS, vastus lateralis mean at 20% BWS,
      soleus duration at 40% BWS); however, these differences did not always achieve
      statistical significance. Slower motor-assisted speeds can be used to accommodate
      weakness of gluteus medius, gluteus maximus, vastus lateralis, medial
      gastrocnemius and soleus. As strength improves, training at faster motor-assisted
      speeds may provide a means to progressively challenge key lower extremity
      stabilizers.

PMID- 23973355
TI  - Sequence and onset of whole-body coordination when turning in response to a
      visual trigger: comparing people with Parkinson's disease and healthy adults.
AB  - Turning round is a routine everyday activity that can often lead to instability.
      The purpose of this study was to investigate abnormalities of turning among
      people with Parkinson's disease (PwPD) through the measurement of sequence of
      body segments and latency response. Participants were asked to turn 180 degrees 
      and whole-body movements were recorded using CODAmotion and Visio Fast eye
      tracking equipment. Thirty-one independently mobile PwPD and 15 age-matched
      healthy controls participated in the study. We found that contrary to common
      belief, the head preceded movement of all other body segments (eyes, shoulders,
      pelvis, first and second foot). We also found interaction between group and body
      segment (P=0.005), indicating that overall, PwPD took longer to move from head to
      second foot than age-matched healthy controls. For PwPD only, interactions were
      found between disease severity and body segment (P<0.0001), between age group and
      body segment (P<0.0001) and between gender and body segments (P<0.0001). For each
      interaction, longer time periods were noted between moving the first foot after
      the pelvis, and moving the second foot after the first, and this was noted for
      PwPD in Hoehn and Yahr stage III-IV (in comparison to Hoehn and Yahr stage I-II);
      for PwPD who were under 70 years (in comparison with 70 years or over); and for
      ladies (in comparison with men). Our results indicate that in PwPD and healthy
      elderly, turning-on-the-spot might not follow the top-to-bottom approach we know
      from previous research.

PMID- 23973356
TI  - Sensitivity of sensor-based sit-to-stand peak power to the effects of training
      leg strength, leg power and balance in older adults.
AB  - Increasing leg strength, leg power and overall balance can improve mobility and
      reduce fall risk. Sensor-based assessment of peak power during the sit-to-stand
      (STS) transfer may be useful for detecting changes in mobility and fall risk.
      Therefore, this study investigated whether sensor-based STS peak power and
      related measures are sensitive to the effects of increasing leg strength, leg
      power and overall balance in older adults. A further aim was to compare
      sensitivity between sensor-based STS measures and standard clinical measures of
      leg strength, leg power, balance, mobility and fall risk, following an exercise
      based intervention. To achieve these aims, 26 older adults (age: 70-84 years)
      participated in an eight-week exercise program aimed at improving leg strength,
      leg power and balance. Before and after the intervention, performance on normal
      and fast STS transfers was evaluated with a hybrid motion sensor worn on the hip.
      In addition, standard clinical tests (isometric quadriceps strength, Timed Up and
      Go test, Berg Balance Scale) were performed. Standard clinical tests as well as
      sensor-based measures of peak power, maximal velocity and duration of normal and
      fast STS showed significant improvements. Sensor-based measurement of peak power,
      maximal velocity and duration of normal STS demonstrated a higher sensitivity
      (absolute standardized response mean (SRM): >= 0.69) to the effects of training
      leg strength, leg power and balance than standard clinical measures (absolute
      SRM: <= 0.61). Therefore, the presented sensor-based method appears to be useful
      for detecting changes in mobility and fall risk.

PMID- 23973357
TI  - Somatotopy of nociceptive responses in the human spinal cord.

PMID- 23973358
TI  - A novel biological role for the phospholipid lysophosphatidylinositol in
      nociceptive sensitization via activation of diverse G-protein signalling pathways
      in sensory nerves in vivo.
AB  - The rich diversity of lipids and the specific signalling pathways they recruit
      provides tremendous scope for modulation of biological functions.
      Lysophosphatidylinositol (LPI) is emerging as a key modulator of cell
      proliferation, migration, and function, and holds important pathophysiological
      implications due to its high levels in diseased tissues, such as in cancer. Here
      we report a novel role for LPI in sensitization of peripheral sensory neurons,
      which was evident as exaggerated sensitivity to painful and innocuous pressure.
      Histopathological analyses indicated lack of involvement of myelin pathology and
      immune cell recruitment by LPI. Using pharmacological and conditional genetic
      tools in mice, we delineated receptor-mediated from non-receptor-mediated effects
      of LPI and we observed that GPR55, which functions as an LPI receptor when
      heterologously expressed in mammalian cells, only partially mediates LPI-induced
      actions in the context of pain sensitization in vivo; we demonstrate that, in
      vivo, LPI functions by activating Galpha(13) as well as Galpha(q/11) arms of G
      protein signalling in sensory neurons. This study thus reports a novel
      pathophysiological function for LPI and elucidates underlying molecular
      mechanisms.

PMID- 23973359
TI  - Multimodal assessment of nervous and immune system responses following sciatic
      nerve injury.
AB  - Subsequent to peripheral nerve compression and irritation, pathophysiological
      processes take place within nervous and immune systems. Here, we utilized a
      multimodal approach to comprehend peripheral and central soft tissue changes as
      well as alterations occurring in systemic analytes following unilateral chronic
      constriction injury (CCI) of the sciatic nerve in rodents. Using magnetic
      resonance imaging and [18F]-2-fluoro-2-deoxy-d-glucose (FDG) positron emission
      tomography, we demonstrated robust structural abnormalities and enhanced FDG
      uptake within the injured nerve and surrounding muscle, respectively. To assess
      whether central morphological changes were induced by nerve injury, diffusion
      tenor imaging was performed. A decrease in fractional anisotropy in primary motor
      cortex contralateral to the injury site was observed. Evaluation of a panel of
      circulating cytokines, chemokines, and growth factors showed decreased levels of
      interleukin-1beta and Fractalkine in CCI animals. Area under the receiver
      operating curve (ROC) calculations of analyte levels, imaging, and behavioral end
      points ranged from 0.786 to 1, where behavioral and peripheral imaging end points
      (eg, FDG uptake in muscle) were observed to have the highest discriminatory
      capabilities (maximum area under ROC = 1) between nerve injury and sham
      conditions. Lastly, performance of correlation analysis involving all analyte,
      behavioral, and imaging data provided an understanding of the overall association
      amongst these end points, and importantly, a distinction in correlation patterns
      was observed between CCI and sham conditions. These findings demonstrate the
      multidimensional pathophysiology of sciatic nerve injury and how a combined
      analyte, behavioral, and imaging assessment can be implemented to probe this
      complexity.

PMID- 23973360
TI  - Response to the letter to the editor by L.A. Avila.

PMID- 23973361
TI  - Response to: Letter from Paul Eugene Summers, Federico Giove, and Carlo Adolfo
      Porro.

PMID- 23973362
TI  - Identification of neuropathic pain in patients with neck/upper limb pain:
      application of a grading system and screening tools.
AB  - The Neuropathic Pain Special Interest Group (NeuPSIG) of the International
      Association for the Study of Pain has proposed a grading system for the presence
      of neuropathic pain (NeP) using the following categories: no NeP, possible,
      probable, or definite NeP. To further evaluate this system, we investigated
      patients with neck/upper limb pain with a suspected nerve lesion, to explore: (i)
      the clinical application of this grading system; (ii) the suitability of 2 NeP
      questionnaires (Leeds Assessment of Neuropathic Symptoms and Signs pain scale
      [LANSS] and the painDETECT questionnaire [PD-Q]) in identifying NeP in this
      patient cohort; and (iii) the level of agreement in identifying NeP between the
      NeuPSIG classification system and 2 NeP questionnaires. Patients (n = 152; age 52
      +/- 12 years; 53% male) completed the PD-Q and LANSS questionnaire and underwent
      a comprehensive clinical examination. The NeuPSIG grading system proved feasible
      for application in this patient cohort, although it required considerable time
      and expertise. Both questionnaires failed to identify a large number of patients
      with clinically classified definite NeP (LANSS sensitivity 22%, specificity 88%;
      PD-Q sensitivity 64%, specificity 62%). These lowered sensitivity scores contrast
      with those from the original PD-Q and LANSS validation studies and may reflect
      differences in the clinical characteristics of the study populations. The
      diagnostic accuracy of LANSS and PD-Q for the identification of NeP in patients
      with neck/upper limb pain appears limited.

PMID- 23973364
TI  - Schistosomiasis research in Africa: how the CONTRAST alliance made it happen.
AB  - In May 2012, the World Health Assembly passed resolution WHA 65.21, calling upon
      member states to intensify schistosomiasis control and, wherever possible, to
      attempt transmission interruption and initiate interventions towards local
      elimination. It is now clear that CONTRAST--a multidisciplinary alliance to
      optimize schistosomiasis control and transmission surveillance in sub-Saharan
      Africa--was ahead of the game. Indeed, launched in October 2006, this 4-year
      project funded by the European Commission made important contributions for
      sustainable schistosomiasis control in the selected African countries through
      innovation, validation and application of new tools and locally adapted
      intervention strategies complementary to preventive chemotherapy. Moreover,
      CONTRAST articulated a research agenda for schistosomiasis elimination, framed by
      10 key questions. Here, we provide a rationale for CONTRAST and discuss its
      overarching goal, the interrelated objectives, establishment and running of a
      research node network across Africa, partnership configuration and modus operandi
      of the project. A collection of 25 articles is presented that are grouped into
      five main themes: molecular, biological, spatial, social and cross-cutting issues
      pertaining to the epidemiology and control of schistosomiasis. We summarize key
      achievements made by CONTRAST, many of which are featured in this special issue
      of Acta Tropica. Together with an independent view put forth by an eminent
      schistosomiasis researcher, the current piece provides an umbrella for the 25
      article collection, including current gaps and remaining research needs. Finally,
      post-CONTRAST initiatives are discussed and a speculative viewpoint is given on
      how schistosomiasis control/elimination will have evolved over the next several
      years.

PMID- 23973363
TI  - Methylphenidate remediates error-preceding activation of the default mode brain
      regions in cocaine-addicted individuals.
AB  - Many previous studies suggest the potential of psychostimulants in improving
      cognitive functioning. Our earlier pharmacological brain imaging study showed
      that intravenous methylphenidate (MPH) improves inhibitory control by altering
      cortico-striato-thalamic activations in cocaine-dependent (CD) individuals. Here
      we provide additional evidence for the effects of MPH in restoring cerebral
      activations during cognitive performance. Ten CD individuals performed a stop
      signal task (SST) during functional magnetic resonance imaging (fMRI) in two
      sessions, in which either MPH (0.5mg/kg body weight) or saline was administered
      intravenously. In the SST, a frequent go signal instructs participants to make a
      speeded response and a less frequent stop signal instructs them to withhold the
      response. Our previous work described increased activation of the
      precuneus/posterior cingulate cortex and ventromedial prefrontal cortex-regions
      of the default mode network (DMN)-before participants committed a stop error in
      healthy control but not CD individuals (Bednarski et al., 2011). The current
      results showed that, compared to saline, MPH restored error-preceding activations
      of DMN regions in CD individuals. The extent of the changes in precuneus activity
      was correlated with MPH-elicited increase in systolic blood pressure. These
      findings suggest that the influence of MPH on cerebral activations may extend
      beyond cognitive control and provide additional evidence warranting future
      studies to investigate the neural mechanisms and physiological markers of the
      efficacy of agonist therapy in cocaine dependence. 

PMID- 23973365
TI  - Girth pressure measurements reveal high peak pressures that can be avoided using
      an alternative girth design that also results in increased limb protraction and
      flexion in the swing phase.
AB  - Girths are frequently blamed for veterinary and performance problems, but
      research into girth/horse interaction is sparse. The study objectives were (1) to
      determine location of peak pressure under a range of girths, and (2) to compare
      horse gait between the horse's standard girth and a girth designed to avoid
      detected peak pressure locations. In the first part of the study, and following
      validation procedures, a calibrated pressure mat placed under the girth of 10
      horses was used to determine the location of peak pressures. A girth was designed
      to avoid peak pressure locations (Girth F). In the second part, 20 elite
      horses/riders with no lameness or performance problem were ridden in Girth F and
      their standard girth (Girth S) in a double blind crossover design. Pressure mat
      data were acquired from under the girths. High speed video was captured and
      forelimb and hindlimb protraction, maximal carpal and tarsal flexion during
      flight were determined in trot. In standard girths, peak pressures were located
      over the musculature behind the elbow. Pressure mat results revealed that the
      maximum forces with Girth S were 22% (left) and 14% (right) greater than Girth F,
      and peak pressures were 76% (left) and 98% (right) greater (P<0.01 for all). On
      gait evaluation, Girth F was associated with 6-11% greater forelimb protraction,
      10-20% greater hindlimb protraction, 4% greater carpal flexion, and 3% greater
      tarsal flexion than Girth S (P<0.01 for all). Peak pressures were located where
      horses tend to develop pressure sores. Girth F reduced peak pressures under the
      girth, and improved limb protraction and carpal/ tarsal flexion, which may
      reflect improved posture and comfort. 

PMID- 23973366
TI  - Circadian and ultradian components of hunger in human non-homeostatic meal-to
      meal eating.
AB  - A unifying physiological explanation of the urge to initiate eating is still not
      available as human hunger in meal-to-meal eating may not be under homeostatic
      control. We hypothesized that a central circadian and a gastrointestinal
      ultradian timing mechanism coordinate non-deprivation meal-to-meal eating. We
      examined hunger as a function of time of day, inter-meal (IM) energy expenditure
      (EE), and concentrations of proposed hunger-controlling hormones ghrelin, leptin,
      and insulin. METHODS: In two crossover studies, 10 postmenopausal women, BMI 23
      26 kg/m(2) engaged in exercise (EX) and sedentary (SED) trials. Weight
      maintenance meals were provided at 6h intervals with an ad libitum meal at 13 h
      in study 1 and 21 h snack in study 2. EE during IM intervals was measured by
      indirect calorimetry and included EX EE of 801 kcal in study 1, and 766-1,051
      kcal in study 2. Hunger was assessed with a visual analog scale and blood was
      collected for hormonal determination. RESULTS: Hunger displayed a circadian
      variation with acrophase at 13 and 19 h and was unrelated to preceding EE. Hunger
      was suppressed by EX between 10 and 16 h and bore no relationship to either EE
      during preceding IM intervals or changes in leptin, insulin, and ghrelin; however
      leptin reflected IM energy changes and ghrelin and insulin, prandial events.
      CONCLUSIONS: During non-deprivation meal-to-meal eating, hunger appears to be
      under non-homeostatic central circadian control as it is unrelated to EE
      preceding meals or concentrations of proposed appetite-controlling hormones.
      Gastrointestinal meal processing appears to intermittently suppress this control
      and entrain an ultradian hunger pattern.

PMID- 23973367
TI  - [Medication safety: nursing at the sharp end].

PMID- 23973368
TI  - Scribble controls NGF-mediated neurite outgrowth in PC12 cells.
AB  - Neurite outgrowth is mediated by dynamic changes of the cytoskeleton and is
      largely controlled by Rho GTPases and their regulators. Here, we show that the
      polarity protein Scribble controls PC12 cell neurite outgrowth in response to
      nerve growth factor. Scribble knockdown decreases neurite numbers and increases
      neurite length. This effect is linked to TrkA the cognate receptor for NGF as
      pharmacological inhibition of phosphorylated TrkA (pTrkA) reduces Scribble
      expression. Moreover, Scribble forms a complex with the MAPK components ERK1/2 in
      a growth factor dependent manner. In RNAi experiments where Scribble expression
      is efficiently depleted sustained ERK1/2 phosphorylation is reduced. Conversely,
      siRNA with intermediate Scribble silencing efficiency fails to match this effect
      indicating that ERK1/2 activation depends on basic Scribble protein levels.
      Finally, Scribble translocates to the plasma membrane in response to growth
      factor where it complexes with HRas and Rac1 suggesting that the phenotype
      activated by loss of Scribble may be a result of altered GTPase activity.
      Together, these results demonstrate a novel role for Scribble in neurite
      outgrowth of PC12 cells. 

PMID- 23973369
TI  - Speech intonation in children with autism spectrum disorder.
AB  - OBJECTIVE: The prosody of children with autism spectrum disorder (ASD) has
      several abnormal features. We assessed the speech tone of children with ASD and
      of children with typical development (TD) by using a new quantitative acoustic
      analysis. METHODS: Our study participants consisted of 63 children (26 with ASD
      and 37 with TD). The participants were divided into 4 groups based on their
      developmental features and age. We assessed the variety of the fundamental
      frequency (F0) pattern quantitatively, using pitch coefficient of variation (CV),
      considering the different F0 mean for each word. RESULTS: (1) No significant
      difference was observed between the ASD and TD group at pre-school age. However,
      the TD group exhibited significantly greater pitch CV than the ASD group at
      school age. (2) In pitch CV, range and standard deviation of the whole speech of
      each participant, no significant differences were observed between the type of
      participants and age. (3) No significant correlation was found between the pitch
      CV of each word and the Japanese Autism Screening Questionnaire total score, or
      between the pitch CV of each word and the intelligence quotient levels in the ASD
      group. A significant correlation was observed between the pitch CV of each word
      and social reciprocal interaction score. CONCLUSIONS: We assessed the speech tone
      of children with ASD by using a new quantitative method. Monotonous speech in
      school-aged children with ASD was detected. The extent of monotonous speech was
      related to the extent of social reciprocal interaction in children with ASD.

PMID- 23973370
TI  - An acid test for g proteins.
AB  - In this issue, Isom et al. (2013) report their exciting discovery that G proteins
      can sense pH changes to fine-tune signaling in response to metabolic changes. 

PMID- 23973371
TI  - Nek8 couples renal ciliopathies to DNA damage and checkpoint control.
AB  - In this issue, Choi et al. (2013) discover a molecular link between the Nek8
      kinase, mutated in the renal ciliopathy nephronophthisis, and DNA damage control
      by cyclin A/Cdk2 and ATR-Chk1, providing new ideas for targeted therapies
      limiting tissue degeneration. 

PMID- 23973372
TI  - MC1R is a potent regulator of PTEN after UV exposure in melanocytes.
AB  - The individuals carrying melanocortin-1 receptor (MC1R) variants, especially
      those associated with red hair color, fair skin, and poor tanning ability (RHC
      trait), are more prone to melanoma; however, the underlying mechanism is poorly
      defined. Here, we report that UVB exposure triggers phosphatase and tensin
      homolog (PTEN) interaction with wild-type (WT), but not RHC-associated MC1R
      variants, which protects PTEN from WWP2-mediated degradation, leading to AKT
      inactivation. Strikingly, the biological consequences of the failure of MC1R
      variants to suppress PI3K/AKT signaling are highly context dependent. In primary
      melanocytes, hyperactivation of PI3K/AKT signaling leads to premature senescence;
      in the presence of BRAF(V600E), MC1R deficiency-induced elevated PI3K/AKT
      signaling drives oncogenic transformation. These studies establish the MC1R-PTEN
      axis as a central regulator for melanocytes' response to UVB exposure and reveal
      the molecular basis underlying the association between MC1R variants and
      melanomagenesis. 

PMID- 23973374
TI  - The logic and mechanism of homologous recombination partner choice.
AB  - Recombinational repair of spontaneous double-strand breaks (DSBs) exhibits sister
      bias. DSB-initiated meiotic recombination exhibits homolog bias. Physical
      analysis in yeast reveals that, in both cases, the recombination reaction
      intrinsically gives homolog bias. From this baseline default, cohesin intervenes
      to confer sister bias, likely independent of cohesion. In meiosis, cohesin's
      sister-biasing effect is counteracted by RecA homolog Rad51 and its mediators,
      plus meiotic RecA homolog Dmc1, which thereby restore intrinsic homolog bias.
      Meiotic axis complex Red1/Mek1/Hop1 participates by cleanly switching
      recombination from mitotic to meiotic mode, concomitantly activating Dmc1. We
      propose that a Rad51/DNA filament at one DSB end captures the intact sister,
      creating an anchor pad. This filament extends across the DSB site on the intact
      partner, precluding intersister strand exchange, thus forcing use of the homolog.
      Cohesin and Dmc1 interactively modulate this extension, with program-appropriate
      effects. In accord with this model, Rad51-mediated recombination in vivo requires
      the presence of a sister. 

PMID- 23973373
TI  - NEK8 links the ATR-regulated replication stress response and S phase CDK activity
      to renal ciliopathies.
AB  - Renal ciliopathies are a leading cause of kidney failure, but their exact
      etiology is poorly understood. NEK8/NPHP9 is a ciliary kinase associated with two
      renal ciliopathies in humans and mice, nephronophthisis (NPHP) and polycystic
      kidney disease. Here, we identify NEK8 as a key effector of the ATR-mediated
      replication stress response. Cells lacking NEK8 form spontaneous DNA double
      strand breaks (DSBs) that further accumulate when replication forks stall, and
      they exhibit reduced fork rates, unscheduled origin firing, and increased
      replication fork collapse. NEK8 suppresses DSB formation by limiting cyclin A
      associated CDK activity. Strikingly, a mutation in NEK8 that is associated with
      renal ciliopathies affects its genome maintenance functions. Moreover, kidneys of
      NEK8 mutant mice accumulate DNA damage, and loss of NEK8 or replication stress
      similarly disrupts renal cell architecture in a 3D-culture system. Thus, NEK8 is
      a critical component of the DNA damage response that links replication stress
      with cystic kidney disorders. 

PMID- 23973375
TI  - Enhanced chromatin dynamics by FACT promotes transcriptional restart after UV
      induced DNA damage.
AB  - Chromatin remodeling is tightly linked to all DNA-transacting activities. To
      study chromatin remodeling during DNA repair, we established quantitative
      fluorescence imaging methods to measure the exchange of histones in chromatin in
      living cells. We show that particularly H2A and H2B are evicted and replaced at
      an accelerated pace at sites of UV-induced DNA damage. This accelerated exchange
      of H2A/H2B is facilitated by SPT16, one of the two subunits of the histone
      chaperone FACT (facilitates chromatin transcription) but largely independent of
      its partner SSRP1. Interestingly, SPT16 is targeted to sites of UV light-induced
      DNA damage-arrested transcription and is required for efficient restart of RNA
      synthesis upon damage removal. Together, our data uncover an important role for
      chromatin dynamics at the crossroads of transcription and the UV-induced DNA
      damage response. 

PMID- 23973376
TI  - Gene-specific transcriptional mechanisms at the histone gene cluster revealed by
      single-cell imaging.
AB  - To bridge the gap between in vivo and in vitro molecular mechanisms, we dissected
      the transcriptional control of the endogenous histone gene cluster (His-C) by
      single-cell imaging. A combination of quantitative immunofluorescence, RNA FISH,
      and FRAP measurements revealed atypical promoter recognition complexes and
      differential transcription kinetics directing histone H1 versus core histone gene
      expression. While H1 is transcribed throughout S phase, core histones are only
      transcribed in a short pulse during early S phase. Surprisingly, no TFIIB or
      TFIID was detectable or functionally required at the initiation complexes of
      these promoters. Instead, a highly stable, preloaded TBP/TFIIA "pioneer" complex
      primes the rapid initiation of His-C transcription during early S phase. These
      results provide mechanistic insights for the role of gene-specific core promoter
      factors and implications for cell cycle-regulated gene expression. 

PMID- 23973377
TI  - The complexity of human ribosome biogenesis revealed by systematic nucleolar
      screening of Pre-rRNA processing factors.
AB  - Mature ribosomal RNAs (rRNAs) are produced from polycistronic precursors
      following complex processing. Precursor (pre)-rRNA processing has been
      extensively characterized in yeast and was assumed to be conserved in humans. We
      functionally characterized 625 nucleolar proteins in HeLa cells and identified
      286 required for processing, including 74 without a yeast homolog. For selected
      candidates, we demonstrated that pre-rRNA processing defects are conserved in
      different cell types (including primary cells), defects are not due to activation
      of a p53-dependent nucleolar tumor surveillance pathway, and they precede cell
      cycle arrest and apoptosis. We also investigated the exosome's role in processing
      internal transcribed spacers (ITSs) and report that 3' end maturation of 18S rRNA
      involves EXOSC10/Rrp6, a yeast ITS2 processing factor. We conclude that human
      cells adopt unique strategies and recruit distinct trans-acting factors to carry
      out essential processing steps, posing fundamental implications for understanding
      ribosomopathies at the molecular level and developing effective therapeutic
      agents. 

PMID- 23973378
TI  - Intradialytic clearance of opioids: methadone versus hydromorphone.
AB  - Opioids are commonly prescribed to patients with chronic pain associated with end
      stage renal disease requiring hemodialysis. The stability of opioid analgesia
      during dialysis may vary among different opioids. No studies to date have
      corroborated this clinical observation by directly comparing plasma
      concentrations of different opioids during dialysis. We compared changes in
      peridialysis plasma concentrations of 2 pharmacokinetically distinct opioids,
      methadone and hydromorphone (HM). Fourteen dialysis patients with chronic pain
      received either methadone or HM for at least 2 weeks before beginning the study.
      Blood samples were obtained immediately before, during, and after hemodialysis in
      2 separate dialysis sessions, 1 week apart, and were analyzed for opioid
      concentrations. Methadone plasma concentrations were more stable during
      hemodialysis compared to HM: the mean percent change of methadone plasma levels
      was 14.9% +/- 8.2% (+/- SD) compared with 55.1% +/- 8.1% in the HM treatment
      group, a difference of 40.2% (95% confidence interval 17.14 to 63.14). The mean
      plasma clearance of methadone was 19.9 +/- 8.5 mL/min (+/- SD) compared with
      105.7 +/- 8.3 mL/min for HM, a difference of 85.7 mL/min (95% confidence interval
      61.9 to 109.1). There were no differences between the 2 opioid groups in pain
      scores, side effect profile, and quality of life. Methadone therapy was not
      associated with an increased rate of adverse events. If confirmed by larger
      clinical studies, methadone could be considered as one of the opioids of choice
      in dialysis patients.

PMID- 23973379
TI  - Impact of cyadox on human colonic microflora in chemostat models.
AB  - The aim of this study was to evaluate the microbiological safety of cyadox, a new
      member of quinoxaline-1,4-dioxides (QdNOs), on human intestinal flora. Four
      chemostats containing human fecal flora were exposed to 0, 16, 32, and 128 MUg/mL
      of cyadox, respectively. Bacterial populations, resistance rates of two
      predominant bacteria and short-chain fatty acids (SCFA) were monitored daily
      prior to and during drug MOA Laboratory of Risk Assessment for Quality and Safety
      of Livestock and Poultry Products exposure. Colonization resistance (CR) of each
      community was determined by three successive daily challenges of Salmonella
      typhimurium. Efflux pump gene (oqxAB) in the Escherichia coli and Enterococcus
      strains were analyzed by PCR amplification and DNA sequencing. No change in SCFA
      was observed after exposure to different concentrations of cyadox. Lower
      concentration of cyadox (16 MUg/mL) had no adverse effect on human microflora.
      However, higher concentrations of cyadox (32 and 128 MUg/mL) could change
      bacterial population and increase the proportion of resistant E. coli and
      Enterococcus. More than 26% (12/46) of cyadox resistant E. coli strains contained
      oqxAB gene, while all the resistant Enterococcus were negative to oqxAB gene.
      Relationship between the occurrence of oqxAB gene and cyadox exposure is
      inconclusive. Our data indicated that 16 MUg/mL might be the no observed effect
      concentration (NOEC) of cyadox. Derived microbiological acceptable daily intake
      (mADI) would be 1552.03 MUg/kg d. The data obtained in present study indicated
      that cyadox was a safe member of QdNOs family of antimicrobial agents.

PMID- 23973380
TI  - Cryptosporidiosis and Cryptosporidium species in animals and humans: a thirty
      colour rainbow?
AB  - Parasites of the genus Cryptosporidium (Apicomplexa) cause cryptosporidiosis in
      humans and animals worldwide. The species names used for Cryptosporidium spp. are
      confusing for parasitologists and even more so for non-specialists. Here, 30
      named species of the genus Cryptosporidium are reviewed and proposed as valid.
      Molecular and experimental evidence suggests that humans and cattle are the hosts
      for 14 and 13 out of 30 named species, respectively. Two, four and eight named
      species are considered of major, moderate and minor public health significance,
      respectively. There are at least nine named species that are shared between
      humans and cattle. The aim of this review is to outline available species
      information together with the most commonly used genetic markers enabling the
      identification of named Cryptosporidium spp. Currently, 28 of 30 named species
      can be identified using the complete or partial ssrRNA, serving as a
      retrospective 'barcode'. Currently, the ssrRNA satisfies the implicit assumption
      that the reference databases used for comparison are sufficiently complete and
      applicable across the whole genus. However, due to unreliable annotation in
      public DNA repositories, the reference nucleotide entries and alignment of named
      Cryptosporidium spp. has been compiled. Despite its known limitations, ssrRNA
      remains the optimal marker for species identification. 

PMID- 23973381
TI  - Electrotransfer of the epinecidin-1 gene into skeletal muscle enhances the
      antibacterial and immunomodulatory functions of a marine fish, grouper
      (Epinephelus coioides).
AB  - Electrotransfer of plasmid DNA into skeletal muscle is a common non-viral
      delivery system for the study of gene function and for gene therapy. However, the
      effects of epinecidin-1 (epi) on bacterial growth and immune system modulation
      following its electrotransfer into the muscle of grouper (Epinephelus coioides),
      a marine fish species, have not been addressed. In this study, pCMV-gfp-epi
      plasmid was electroporated into grouper muscle, and its effect on subsequent
      infection with Vibrio vulnificus was examined. Over-expression of epi efficiently
      reduced bacterial numbers at 24 and 48 h after infection, and augmented the
      expression of immune-related genes in muscle and liver, inducing a moderate
      innate immune response associated with pro-inflammatory infiltration.
      Furthermore, electroporation of pCMV-gfp-epi plasmid without V. vulnificus
      infection induced moderate expression of certain immune-related genes,
      particularly innate immune genes. These data suggest that electroporation
      mediated gene transfer of epi into the muscle of grouper may hold potential as an
      antimicrobial therapy for pathogen infection in marine fish.

PMID- 23973382
TI  - Effect of dietary supplemented andrographolide on growth, non-specific immune
      parameters and resistance against Aeromonas hydrophila in Labeo rohita
      (Hamilton).
AB  - The present study evaluated the effect of dietary andrographolide (EC 50%) on
      growth, non-specific immune parameters and disease resistance against Aeromonas
      hydrophila infection in Indian major carp, Labeo rohita fingerlings. Fishes were
      fed with formulated diet containing andrographolide as T0 (0.00%), T1 (0.05%), T2
      (0.10%), T3 (0.20%), T4 (0.40%) and T5 (0.80%) for 42 days. Fishes were
      challenged with A. hydrophila 42 days post feeding and relative percentage
      survival (RPS) was recorded over 14 days post challenge. Blood and serum samples
      were collected for nonspecific immune parameters on 14, 28 and 42 days of feeding
      and growth performance was evaluated at the end of experiment. The results
      revealed that fishes fed with andrographolide showed significant (p < 0.05)
      increase in NBT levels, myeloperoxidase activity, phagocytic activity, serum
      lysozyme activity, and serum antiprotease activity when compared to the control
      group. The weight gain, specific growth rate, feed conversion ratio and protein
      efficiency ratio of fishes fed with andrographolide were found to be
      significantly (p < 0.05) differed compared with control. Dietary andrographolide
      at the level of 0.10% showed significantly (P < 0.05) higher RPS (74.06%) against
      A. hydrophila infection than control. The results revealed that andrographolide
      supplemented diet has a stimulatory effect on non-specific immune parameters
      along with improved growth performance and increased disease resistance against
      A. hydrophila infection in L. rohita fingerlings.

PMID- 23973383
TI  - Carcinogenic liver fluke Opisthorchis viverrini oxysterols detected by LC-MS/MS
      survey of soluble fraction parasite extract.
AB  - Liquid chromatography in tandem mass spectrometry (LC-MS/MS) has emerged as an
      informative tool to investigate oxysterols (oxidized derivatives of cholesterol)
      in helminth parasite associated cancers. Here, we used LC-MS/MS to investigate in
      soluble extracts of the adult developmental stage of Opisthorchis viverrini from
      experimentally infected hamsters. Using comparisons with known bile acids and the
      metabolites of estrogens, the LC-MS data indicated the existence of novel
      oxysterol derivatives in O. viverrini. Most of these derivatives were ramified at
      C-17, in similar fashion to bile acids and their conjugated salts. Several were
      compatible with the presence of an estrogen core, and/or hydroxylation of the
      steroid aromatic ring A, hydroxylation of both C-2 and C-3 of the steroid ring
      and further oxidation into an estradiol-2,3-quinone. 

PMID- 23973384
TI  - Near-infrared spectroscopy to detect absence of cerebrovascular autoregulation in
      preterm infants.
AB  - OBJECTIVE: Our aim was to explore clinical parameters that might predict the
      absence of cerebrovascular autoregulation (CAR) assessed by a negative
      relationship between mean arterial blood pressure (MABP) and fractional tissue
      oxygen extraction (FTOE) as measured by near-infared spectroscopy (NIRS) in
      preterm infants. METHODS: We included preterm infants (gestational age (GA) <32
      weeks). Within 72 h after birth, we recorded the infants' NIRS parameters and
      MABP for a 24-h period. Fractional tissue oxygen extraction (FTOE) was
      calculated. For each infant we calculated Spearman rank (rho) correlations. A
      statistically significant negative correlation between MABP and FTOE indicated
      the absent CAR. We related the absent CAR to clinical parameters. RESULTS: Ten
      (40%) out of 25 infants (median GA 29.1 weeks, range 25.4-31.7, birth weight 1245
      g, 560-1780) had a statistically significant negative correlation between MABP
      and FTOE (rho -0.432 to -0.156), suggesting the absence of CAR. None of the
      clinical variables predicted the absence of CAR. CONCLUSIONS: We were unable to
      predict the absence of CAR in terms of clinical variables. Nevertheless, we found
      a statistically significant negative correlation between MABP and FTOE using
      NIRS, suggesting the absence of CAR in almost half of the preterm infants
      studied. SIGNIFICANCE: NIRS could be a helpful tool to assess the presence or
      absence of CAR.

PMID- 23973385
TI  - Bortezomib-induced neuropathy: axonal membrane depolarization precedes
      development of neuropathy.
AB  - OBJECTIVE: Bortezomib is a proteasome inhibitor with high efficacy for multiple
      myeloma but with severe peripheral neurotoxicity, leading to dose modification
      and severe neurological disability. This study aimed to investigate the
      pathophysiology of bortezomib-induced neuropathy. METHODS: Threshold tracking was
      used to assess the excitability of sensory and motor axons. Measurements were
      sequentially performed before and after bortezomib treatment in nine patients
      with newly diagnosed multiple myeloma. RESULTS: In total, 67% of patients finally
      developed symptomatic neuropathy. Changes in sensory axonal excitability indices
      readily occurred after the first course of administration. Patterns of changes in
      excitability indices suggest membrane depolarization (decreased
      superexcitability, P<0.001; decreased depolarizing threshold electrotonus 90
      100ms, P=0.02). Abnormalities in nerve conduction parameters suggestive of axonal
      degeneration appeared after the second course of treatment. CONCLUSIONS:
      Bortezomib induces a depolarizing shift in resting membrane potential prior to
      the development of neuropathy. Membrane depolarization could be associated with
      impairment of electrogenic Na(+)-K(+)-ATPase-dependent pump caused by toxic
      effects of bortezomib on mitochondria. SIGNIFICANCE: Axonal depolarization and
      hyperexcitability might enhance neurodegeneration in bortezomib-induced
      neuropathy.

PMID- 23973386
TI  - Music and academic performance.
AB  - In a previous study we demonstrated that listening to a pleasant music while
      performing an academic test helped students to overcome stress, to devote more
      time to more stressful and more complicated task and the grades were higher. Yet,
      there remained ambiguities as for the causes of the higher test performance of
      these students: do they perform better because they hear music during their
      examinations, or would they perform better anyway because they are more
      gifted/motivated? This motivated the current study as a preliminary step toward
      that general question: Do students who like/perform music have better grades than
      the others? Our results confirmed this hypothesis: students studying music have
      better grades in all subjects. 

PMID- 23973387
TI  - Androgen receptor distribution in the social decision-making network of eusocial
      naked mole-rats.
AB  - Naked mole-rats are highly social rodents that live in large groups and exhibit a
      strict reproductive and social hierarchy. Only a few animals in each colony
      breed; the remainder are non-reproductive and are socially subordinate to
      breeders. We have examined androgen receptor immunoreactive (AR+) cells in brain
      regions comprising the recently described social decision-making network in
      subordinate and breeder naked mole-rats of both sexes. We find that subordinates
      have a significantly higher percentage of AR+ cells in all brain regions
      expressing this protein. By contrast, there were no significant effects of sex
      and no sex-by-status interactions on the percentage of AR+ cells. Taken together
      with previous findings, the present data complete a systematic assessment of the
      distribution of AR protein in the social decision-making network of the eusocial
      mammalian brain and demonstrate a significant role for social status in the
      regulation of this protein throughout many nodes of this network. 

PMID- 23973388
TI  - Inherited genetic susceptibility to breast cancer: the beginning of the end or
      the end of the beginning?
AB  - Genome-wide association studies have identified 72 loci associated with breast
      cancer susceptibility. Seventeen of these are known to predispose to other
      cancers. High-penetrance susceptibility loci for breast cancer usually result
      from coding alterations, principally in genes involved in DNA repair, whereas
      almost all of the associations identified through genome-wide association studies
      are found in noncoding regions of the genome and are likely to involve regulation
      of genes in multiple pathways. However, the genes underlying most associations
      are not yet known. In this review, we summarize the findings from genome-wide
      association studies in breast cancer and describe the genes and mechanisms that
      are likely to be involved in the tumorigenesis process. We also discuss
      approaches to fine-scale mapping of susceptibility regions used to identify the
      likely causal variant(s) underlying the associations, a major challenge in
      genetic epidemiology. Finally, we discuss the potential impact of such findings
      on personalized medicine and future avenues for screening, prediction, and
      prevention programs. 

PMID- 23973389
TI  - Micro-Raman spectroscopy shows how the coating process affects the
      characteristics of hydroxylapatite.
AB  - The diversity in the structural and chemical state of apatites allows implant
      manufacturers to fine-tune implant properties. This requires suitable
      manufacturing processes and characterization tools to adjust the amorphous phase
      and hydroxyl content from the source hydroxylapatite. Hydroxylapatite was
      processed by high-velocity oxy-fuel spraying, plasma spraying and flame spraying,
      and primarily analyzed by Raman spectroscopy. Investigation of rounded splats,
      the building blocks of thermal spray coatings, allowed correlation between the
      visual identity of the splat surface and the Raman spectra. Splats were heat
      treated to crystallize any remaining amorphous phase. The nu1 PO4 stretching peak
      at 950-970 cm(-1) displayed the crystalline order, but the hydroxyl peak at 3572
      cm(-1) followed the degree of dehydroxylation. Hydroxyl loss was greatest for
      flame-sprayed particles, which create the longest residence time for the melted
      particle. Higher-frequency hydroxyl peaks in flame- and plasma-sprayed splats
      indicated a lower structural order for the recrystallized hydroxylapatite within
      the splats. Crystallization at 700  degrees C has shown potential for revealing
      hydroxyl ions previously trapped in amorphous calcium phosphate. This work
      compares Fourier transform infrared and Raman spectroscopy to measure the
      hydroxyl content in rapidly solidified apatites and shows that Raman spectroscopy
      is more suitable.

PMID- 23973390
TI  - In vitro hemocompatibility and vascular endothelial cell functionality on titania
      nanostructures under static and dynamic conditions for improved coronary stenting
      applications.
AB  - The usefulness of nanoscale topography in improving vascular response in vitro
      was established previously on hydrothermally modified titanium surfaces. To
      propose this strategy of surface modification for translation onto clinically
      used metallic stents, it is imperative that the surface should be also
      hemocompatible: an essential attribute for any blood-contacting device. The
      present in vitro study focuses on a detailed hemocompatibility evaluation of
      titania nanostructures created through an alkaline hydrothermal route on metallic
      Ti stent prototypes. Direct interactions of TiO2 nanocues of various morphologies
      with whole blood were studied under static conditions as well as using an in
      vitro circulation model mimicking arterial flow, with respect to a polished Ti
      control. Nanomodified stent surfaces upon contact with human blood showed
      negligible hemolysis under constant shear and static conditions. Coagulation
      profile testing indicated that surface roughness of nanomodified stents induced
      no alterations in the normal clotting times, with insignificant thrombus
      formation and minimal inflammatory reaction. Endothelialized nanomodified Ti
      surfaces were found to inhibit both activation as well as aggregation of
      platelets compared with the control surface, with the endothelium formed on the
      nanosurfaces having an increased expression of anti-thrombogenic genes. Such a
      nanotextured Ti surface, which is anti-thrombogenic and promotes
      endothelialization, would be a cost-effective alternative to drug-eluting stents
      or polymer-coated stents for overcoming in-stent restenosis.

PMID- 23973392
TI  - Increased yield of biotransformation of exemestane with beta-cyclodextrin
      complexation technique.
AB  - In this study, 6-methylenandrosta-4-ene-3,17-dione and Hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) were used to form a complex, which could be then
      biotransformed by Arthrobacter simplex ATCC6946 to obtain the antitumor drug
      exemestane. The complex was analyzed by UV, DSC and TG techniques, while the
      products were analyzed by HPLC, NMR and MS. These results confirmed that the beta
      cyclodextrin not only improved the water-solubility of 6-methylenandrosta-4-ene
      3,17-dione, but also greatly enhanced the biocompatibility during the
      biotransformation process. This result may be applied to other precursors which
      have poor aqueous solubility in the biotransformation processes. 

PMID- 23973393
TI  - Predator attack rate evolution in space: the role of ecology mediated by complex
      emergent spatial structure and self-shading.
AB  - Predation interactions are an important element of ecological communities.
      Population spatial structure has been shown to influence predator evolution,
      resulting in the evolution of a reduced predator attack rate; however, the
      evolutionary role of traits governing predator and prey ecology is unknown. The
      evolutionary effect of spatial structure on a predator's attack rate has
      primarily been explored assuming a fixed metapopulation spatial structure, and
      understood in terms of group selection. But endogenously generated, emergent
      spatial structure is common in nature. Furthermore, the evolutionary influence of
      ecological traits may be mediated through the spatial self-structuring process.
      Drawing from theory on pathogens, the evolutionary effect of emergent spatial
      structure can be understood in terms of self-shading, where a voracious predator
      limits its long-term invasion potential by reducing local prey availability. Here
      we formalize the effects of self-shading for predators using spatial moment
      equations. Then, through simulations, we show that in a spatial context self
      shading leads to relationships between predator-prey ecology and the predator's
      attack rate that are not expected in a non-spatial context. Some relationships
      are analogous to relationships already shown for host-pathogen interactions, but
      others represent new trait dimensions. Finally, since understanding the effects
      of ecology using existing self-shading theory requires simplifications of the
      emergent spatial structure that do not apply well here, we also develop metrics
      describing the complex spatial structure of the predator and prey populations to
      help us explain the evolutionary effect of predator and prey ecology in the
      context of self-shading. The identification of these metrics may provide a step
      towards expansion of the predictive domain of self-shading theory to more complex
      spatial dynamics. 

PMID- 23973391
TI  - Electrospun scaffolds for tissue engineering of vascular grafts.
AB  - There is a growing demand for off-the-shelf tissue engineered vascular grafts
      (TEVGs) for the replacement or bypass of damaged arteries in various
      cardiovascular diseases. Scaffolds from the decellularized tissue skeletons to
      biopolymers and biodegradable synthetic polymers have been used for fabricating
      TEVGs. However, several issues have not yet been resolved, which include the
      inability to mimic the mechanical properties of native tissues, and the ability
      for long-term patency and growth required for in vivo function. Electrospinning
      is a popular technique for the production of scaffolds that has the potential to
      address these issues. However, its application to human TEVGs has not yet been
      achieved. This review provides an overview of tubular scaffolds that have been
      prepared by electrospinning with potential for TEVG applications. 

PMID- 23973394
TI  - Reply: To PMID 23659988.

PMID- 23973395
TI  - Progress of labor in women induced with misoprostol vs the Foley catheter.

PMID- 23973396
TI  - The association of dysmenorrhea with noncyclic pelvic pain accounting for
      psychological factors.
AB  - OBJECTIVE: The factors that underlie pelvic pain are poorly understood.
      Specifically, the relative influence of dysmenorrhea and psychological factors in
      the etiology of noncyclic pelvic pain conditions, such as interstitial cystitis
      and irritable bowel syndrome, is unknown. To further characterize pelvic pain, we
      compared the frequency of menstrual, somatosensory, and psychological risk
      factors between women with and without severe noncyclic pelvic pain symptoms.
      STUDY DESIGN: A total of 1012 reproductive-aged women completed a 112-item
      questionnaire with domains including mood, fatigue, physical activity, somatic
      complaint, and pain. Questionnaire items included existing items for menstrual
      distress and newly written items derived from qualitative interviews. The
      relationship of dysmenorrhea and noncyclic pelvic pain complaints (dyspareunia,
      dyschezia, or dysuria) was modeled using quantile regression. RESULTS: Among
      women who menstruate regularly, those with dysmenorrhea had disproportionally
      more severe noncyclic pelvic pain (54/402, 13%) than women without dysmenorrhea
      (5/432, 1%; odds ratio, 13; 95% confidence interval, 5-33). In a multivariate
      adjusted model, dysmenorrhea (beta = .17), activity capability (beta = .17),
      somatic complaint (beta = .17), and bodily pain (beta = .12) were the primary
      predictors of noncyclic pelvic pain. Depression (beta = .03) and anxiety (beta =
      .01) were not significantly predictive. The presence of dysmenorrhea, somatic
      complaint, and low activity capability predicted 90% of the cases of women with
      noncyclic pelvic pain. CONCLUSION: The association between dysmenorrhea and
      noncyclic pelvic pain suggests that menstrual pain is an etiological factor in
      noncyclic pelvic pain, whereas depression and anxiety may be secondary effects.
      Longitudinal studies are needed to determine whether dysmenorrhea causally
      influences development of noncyclic pelvic pain or shares common underlying
      neural mechanisms.

PMID- 23973397
TI  - Reply: To PMID 23467050.

PMID- 23973398
TI  - Incidence of preeclampsia: risk factors and outcomes associated with early-
      versus late-onset disease.
AB  - OBJECTIVE: The population-based incidence of early-onset (<34 weeks) and late
      onset preeclampsia (>=34 weeks) has not been adequately studied. We examined the
      gestational age-specific incidence of preeclampsia onset and identified the
      associated risk factors and birth outcomes. STUDY DESIGN: All singleton
      deliveries in Washington State, 2003-2008 (n = 456,668), were included, and
      preeclampsia onset was determined from hospital records linked to birth
      certificates. Cox and logistic regression models were used to obtain adjusted
      hazard ratios and odds ratios (AORs) for risk factors and birth outcomes,
      respectively. RESULTS: The overall preeclampsia rate was 3.1% and the incidence
      increased sharply with gestation; early- and late-onset preeclampsia rates were
      0.38% and 2.72%, respectively. Among women with early-onset preeclampsia, 12%
      delivered at a gestation of 34 weeks or longer. Risk/protective factors common to
      both diseases included older maternal age, Hispanic and Native-American race,
      smoking, unmarried status, and male fetus. African-American race, chronic
      hypertension, and congenital anomalies were more strongly associated with early
      onset preeclampsia, whereas younger maternal age, nulliparity, and diabetes
      mellitus were more strongly associated with late-onset disease. Early- but not
      late-onset preeclampsia conferred a high risk of fetal death (AOR, 5.8; 95%
      confidence interval [CI], 4.0-8.3 vs AOR, 1.3; 95% CI, 0.8-2.0, respectively).
      The AOR for perinatal death/severe neonatal morbidity was 16.4 (95% CI, 14.5
      18.6) in early-onset and 2.0 (95% CI, 1.8-2.3) in late-onset preeclampsia.
      CONCLUSION: Early- and late-onset preeclampsia shares some etiological features,
      differ with regard to several risk factors, and lead to different outcomes. The 2
      preeclampsia types should be treated as distinct entities from an etiological and
      prognostic standpoint.

PMID- 23973399
TI  - Panton-Valentine leukocidin producing Staphylococcus aureus nasal carriage, in
      North-Lebanon.
AB  - OBJECTIVES: We investigated the prevalence and the risk factors of nasal carriage
      of Staphylococcus aureus carrying Panton-Valentine leukocidin genes [Sa PVL(+)]
      in pupils. STUDY POPULATION AND METHODS: Two hundred and fifty-seven pupils were
      screened by nasal swabbing. The detection of 16S rRNA, mecA and luk-PV genes was
      performed by PCR and the risk factors were assessed with the statistical analysis
      of a questionnaire. RESULTS: Thirty-one percent of pupils were colonized, with
      16.4% of isolates carrying the luk-PV gene and 8.8% the mecA gene. Children aged
      7years or more and living in a boarding school were the factors promoting nasal
      carriage 60% of children who presented with an abscess in the previous year were
      carriers of luk-PV gene Sa. CONCLUSION: The study revealed a high prevalence of
      luk-PV gene among methicillin-susceptible strains and a statistically significant
      correlation between the presence of this gene and presenting with an abscess.

PMID- 23973400
TI  - Evaluation of a strategy aimed at reducing errors in antiretroviral prescriptions
      for hospitalized HIV-infected patients.
AB  - OBJECTIVES: Errors are frequently made in the prescription of antiretroviral
      medication for hospitalized HIV-infected patients. We had for aim to evaluate the
      prescription of antiretroviral drug regimens at hospital admission and the impact
      of a strategy implemented to prevent errors. METHODS: HIV-infected patients
      managed by our hospital as outpatients and admitted between January 1, 2010, and
      December 31, 2010 (first period) and between February 1, 2011, and January 31,
      2012 (second period) were included in the study. We retrospectively identified
      errors made in the prescription of antiretrovirals by comparing the drugs
      prescribed during hospitalization and the treatment documented in the outpatient
      file. During the second period, we implemented a strategy involving the
      pharmacist and the infectious disease specialist to reduce the number of errors.
      RESULTS: Thirty-five patients were treated during the first period for 56
      admissions, and 43 patients for 77 admissions during the second one. We
      identified 39% of medication-related errors during the first period and 42%
      during the second one. The most common errors were drug omission, inappropriate
      dosage, or failure to adjust dosage for renal insufficiency. Our intervention,
      during the second period, allowed correcting 36% of errors. CONCLUSION: In our
      study, errors made in the prescription of antiretroviral medication were frequent
      and our intervention allowed correcting 36% of errors. Other strategies, such as
      consulting a clinical pharmacist on admission, or training prescribers should be
      considered.

PMID- 23973401
TI  - Cryptococcal meningitis occurring eight years before a diagnosis of lupus was
      made.

PMID- 23973403
TI  - Plant-derived nanoparticle treatment with cocc 30c ameliorates attention and
      motor abilities in sleep-deprived rats.
AB  - Sleep is an essential physiological process that underlies crucial cognitive
      functions as well as emotional reactivity. Thus, sleep deprivation (SD) may exert
      various deleterious effects. In this study, we aimed to examine the adverse
      behavioral and hormonal effects of SD and a potential treatment with Plant
      derived nanoparticle treatment - cocc 30c. The study was a 4-arm trial with
      randomization and double-blinding of verum and placebo treatments. SD was induced
      by using the Multiple Platform Method for 48 h. The effects of SD were evaluated
      behaviorally (pre-pulse inhibition (PPI), startle response and rotor-rod) at
      baseline as well as at 6, 12, 24h, and 14 days post deprivation. cocc 30c
      treatment was administrated Per Os every three hours starting immediately after
      baseline tests and for a period of 24h. On day 14, blood samples were taken and
      serum levels of corticosterone, testosterone, serotonin and leptin were tested.
      We found that cocc 30c improved PPI 12 and 24h post deprivation, likewise, cocc
      30c improved motor learning. On day 14 SD led to increased startle response that
      was ameliorated by cocc 30c. Likewise, SD led to increased levels of
      corticosterone and serotonin while decreasing testosterone and leptin.
      Interestingly, cocc 30c treatment has moderated these hormonal alterations. We
      conclude that the treatment with cocc 30c recovers both short-term behavioral and
      the long-term hormonal modulations following SD.

PMID- 23973402
TI  - Aerobic endurance capacity affects spatial memory and SIRT1 is a potent modulator
      of 8-oxoguanine repair.
AB  - Regular exercise promotes brain function via a wide range of adaptive responses,
      including the increased expression of antioxidant and oxidative DNA damage
      repairing systems. Accumulation of oxidized DNA base lesions and strand breaks is
      etiologically linked to for example aging processes and age-associated diseases.
      Here we tested whether exercise training has an impact on brain function, extent
      of neurogenesis, and expression of 8-oxoguanine DNA glycosylase-1 (Ogg1) and
      SIRT1 (silent mating-type information regulation 2 homolog). To do so, we
      utilized strains of rats with low- and high-running capacity (LCR and HCR) and
      examined learning and memory, DNA synthesis, expression, and post-translational
      modification of Ogg1 hippocampal cells. Our results showed that rats with higher
      aerobic/running capacity had better spatial memory, and expressed less Ogg1, when
      compared to LCR rats. Furthermore, exercise increased SIRT1 expression and
      decreased acetylated Ogg1 (AcOgg1) levels, a post-translational modification
      important for efficient repair of 8-oxo-7,8-dihydroguanine (8-oxoG). Our data on
      cell cultures revealed that nicotinamide, a SIRT1-specific inhibitor, caused the
      greatest increase in the acetylation of Ogg1, a finding further supported by our
      other observations that silencing SIRT1 also markedly increased the levels of
      AcOgg1. These findings imply that high-running capacity is associated with
      increased hippocampal function, and SIRT1 level/activity and inversely correlates
      with AcOgg1 levels and thereby the repair of genomic 8-oxoG.

PMID- 23973404
TI  - A dietary embryo/fetal developmental toxicity study of arruva, an R,R-monatin
      salt isomer, in Crl:CD(SD) rats.
AB  - R,R-Monatin is an intensely sweet substance originally identified in the root
      bark of Sclerochiton ilicifolius. R,R-Monatin salt, commonly known as "arruva",
      has potential for use as a high-potency sweetener food ingredient. Previously,
      arruva was concluded to present no toxicologically relevant effects to Crl:CD(SD)
      rats and Crl:CD-1(ICR) mice fed up to 35,000 ppm arruva in the diet for 90 days.
      In the present study, groups of mated Sprague-Dawley rats (25 Crl:CD(SD)
      females/group) were exposed continuously to 0 (control), 15,000, 30,000, or
      50,000 ppm arruva in the diet during gestation days 6-21. There were no fetal
      malformations or developmental variations that were attributable to arruva at any
      exposure level, nor were there any test article-related effects on intrauterine
      survival. Maternal toxicity, evidenced by lower mean body weights, body weight
      gains and feed efficiency, was observed at 50,000 ppm. A developmental effect, in
      the form of lower mean fetal body weight, was noted in the 50,000 ppm group in
      the presence of maternal toxicity. Therefore, the dietary no-observed-adverse
      effect level (NOAEL) for maternal and embryo/fetal developmental toxicity of
      arruva in pregnant rats during gestation days 6-21 was 30,000 ppm (equivalent to
      2564 mg/kg bw/day) based on reductions in maternal and fetal body weights.

PMID- 23973406
TI  - Stress and salicylic acid induce the expression of PnFT2 in the regulation of the
      stress-induced flowering of Pharbitis nil.
AB  - Poor nutrition and low temperature stress treatments induced flowering in the
      Japanese morning glory Pharbitis nil (synonym Ipomoea nil) cv. Violet. The
      expression of PnFT2, one of two homologs of the floral pathway integrator gene
      FLOWERING LOCUS T (FT), was induced by stress, whereas the expression of both
      PnFT1 and PnFT2 was induced by a short-day treatment. There was no positive
      correlation between the flowering response and the homolog expression of another
      floral pathway integrator gene SUPPRESSOR OF OVEREXPRESSION OF CO1 and genes
      upstream of PnFT, such as CONSTANS. In another cultivar, Tendan, flowering and
      PnFT2 expression were not induced by poor nutrition stress. Aminooxyacetic acid
      (AOA), a phenylalanine ammonia-lyase inhibitor, inhibited the flowering and PnFT2
      expression induced by poor nutrition stress in Violet. Salicylic acid (SA)
      eliminated the inhibitory effects of AOA. SA enhanced PnFT2 expression under the
      poor nutrition stress but not under non-stress conditions. These results suggest
      that SA induces PnFT2 expression, which in turn induces flowering; SA on its own,
      however, may not be sufficient for induction. 

PMID- 23973405
TI  - Dietary predictors of young children's exposure to current-use pesticides using
      urinary biomonitoring.
AB  - Few data exist on the association between dietary habits and urinary biomarker
      concentrations of pesticides in children. The objective was to examined the
      association between the weekly intake frequency of 65 food items and urinary
      biomarkers of exposure to chlorpyrifos (3,5,6-trichloro-2-pyridinol [TCP]),
      permethrin (3-phenoxybenzoic acid [3-PBA]), and 2,4-dichlorophenoxyacetic acid
      [2,4-D] in 135 preschool-aged children. TCP and 3-PBA are nonspecific biomarkers
      as they are also urinary metabolites of other pesticides. TCP, 3-PBA, and 2,4-D
      were detected in 99%, 64%, and 92% of the urine samples, respectively. Mean
      urinary TCP concentrations were statistically significantly higher in children
      consuming fresh apples (9.40+/-15.5 ng/mL versus 5.76+/-3.57 ng/mL, p=0.040) and
      fruit juices (8.41+/-11.5 ng/mL versus 4.11+/-2.77 ng/mL, p=0.020) >=3 times a
      week compared to <3 times a week. For 3-PBA, mean urinary metabolite
      concentrations were statistically significantly greater in children consuming
      chicken/turkey meats (0.79+/-0.81 versus 0.41+/-0.39, p=0.013) >=3 times a week
      compared to <3 times a week. No association occurred between the consumption of
      any food item and children's mean urinary 2,4-D concentrations by intake group.
      In conclusion, frequent consumption of fresh apples and fruit juices or
      chicken/turkey meats were significant dietary predictors of urinary levels of TCP
      or 3-PBA, respectively.

PMID- 23973407
TI  - Are the neural correlates of subitizing and estimation dissociable? An fNIRS
      investigation.
AB  - Human performance in visual enumeration tasks typically shows two distinct
      patterns as a function of set size. For small sets, usually up to 4 items,
      numerosity judgments are extremely rapid, precise and confident, a phenomenon
      known as subitizing. When this limit is exceeded and serial counting is
      precluded, exact enumeration gives way to estimation: performance becomes error
      prone and more variable. Surprisingly, despite the importance of subitizing and
      estimation in numerical cognition, only few neuroimaging studies have examined
      whether the neural activity related to these two phenomena can be dissociated. In
      the present work, we used multi-channel near-infrared spectroscopy (fNIRS) to
      measure hemodynamic activity of the bilateral parieto-occipital cortex during a
      visual enumeration task. Participants had to judge the numerosity of dot arrays
      and indicate it by means of verbal response. We observed a different hemodynamic
      pattern in the parietal cortex, both in terms of amplitude modulation and
      temporal profile, for numerosities below and beyond the subitizing range.
      Crucially, the neural dissociation between subitizing and estimation was
      strongest at the level of right IPS. The present findings confirm that fNIRS can
      be successfully used to detect subtle temporal differences in hemodynamic
      activity and to produce inferences on the neural mechanisms underlying cognitive
      functions. 

PMID- 23973408
TI  - The feedback-related negativity (FRN) revisited: new insights into the
      localization, meaning and network organization.
AB  - Changes in response contingencies require adjusting ones assumptions about
      outcomes of behaviors. Such adaptation processes are driven by reward prediction
      error (RPE) signals which reflect the inadequacy of expectations. Signals
      resembling RPEs are known to be encoded by mesencephalic dopamine neurons
      projecting to the striatum and frontal regions. Although regions that process
      RPEs, such as the dorsal anterior cingulate cortex (dACC), have been identified,
      only indirect evidence links timing and network organization of RPE processing in
      humans. In electroencephalography (EEG), which is well known for its high
      temporal resolution, the feedback-related negativity (FRN) has been suggested to
      reflect RPE processing. Recent studies, however, suggested that the FRN might
      reflect surprise, which would correspond to the absolute, rather than the signed
      RPE signals. Furthermore, the localization of the FRN remains a matter of debate.
      In this simultaneous EEG-functional magnetic resonance imaging (fMRI) study, we
      localized the FRN directly using the superior spatial resolution of fMRI without
      relying on any spatial constraint or other assumption. Using two different single
      trial approaches, we consistently found a cluster within the dACC. One analysis
      revealed additional activations of the salience network. Furthermore, we
      evaluated the effect of signed RPEs and surprise signals on the FRN amplitude. We
      considered that both signals are usually correlated and found that only surprise
      signals modulate the FRN amplitude. Last, we explored the pathway of RPE signals
      using dynamic causal modeling (DCM). We found that the surprise signals are
      directly projected to the source region of the FRN. This finding contradicts
      earlier theories about the network organization of the FRN, but is in line with a
      recent theory stating that dopamine neurons also encode surprise-like saliency
      signals. Our findings crucially advance the understanding of the FRN. We found
      compelling evidence that the FRN originates from the dACC. Furthermore, we
      clarified the functional role of the FRN, and determined the role of the dACC
      within the RPE network. These findings should enable us to study the processing
      of surprise and adjustment signals in the dACC in healthy and also in psychiatric
      patients. 

PMID- 23973409
TI  - A study of the effects of sodium halides on the performance of air-jet and
      vibrating-mesh nebulizers.
AB  - The influence of sodium halide electrolytes on aerosols generated from the
      Aeroneb Pro vibrating mesh nebulizer and the Sidestream air-jet nebulizer has
      been evaluated. Fluids with a range of concentrations of Na halides (i.e. NaF,
      NaCl, NaBr and NaI) were used as nebulizer solutions and their effect on aerosol
      properties such as total aerosol output, fine particle fraction (FPF), volume
      median diameter (VMD) and predicted regional airway deposition were investigated.
      For both nebulizers, the inclusion of electrolyte significantly enhanced the
      aerosol properties compared with HPLC grade (deionized) water. Aerosol output,
      FPF and aerosol fraction less than 2.15 MUm were directly proportional to
      electrolyte concentration. Furthermore, the proportion of aerosols that are
      likely to deposit in the oropharyngeal region, and the VMD of the droplets were
      inversely related to the electrolyte concentration for both nebulizers. In
      general, the inclusion of electrolytes had a greater impact on the aerosol
      properties of the vibrating-mesh nebulizer. In the Aeroneb Pro, NaI 2.0% (w/v)
      was the optimum solution as it generated the highest aerosol output, FPF and
      output fraction below 2.15 MUm with the lowest VMD and minimal predicted
      oropharyngeal deposition. This was attributed to the polarizing ability of iodide
      ions present in the largest quantity at the air-water interface. This study has
      shown that the Aeroneb Pro vibrating-mesh device demonstrated greatly enhanced
      aerosol properties when halides were included in the nebulizer solutions.

PMID- 23973410
TI  - Relationship between the distribution of cefepime minimum inhibitory
      concentrations and detection of extended-spectrum beta-lactamase production among
      clinically important Enterobacteriaceae isolates obtained from patients in
      intensive care units in Taiwan: results from the Surveillance of Multicenter
      Antimicrobial Resistance in Taiwan (SMART) in 2007.
AB  - BACKGROUND: The data on susceptibility of important cephalosporins against four
      Enterobacteriaceae members producing potential extended-spectrum beta-lactamase
      (ESBL) collected from Taiwanese intensive care units are lacking. METHODS:
      Minimum inhibitory concentrations (MICs) of cefotaxime, ceftazidime, and cefepime
      were determined using agar dilution method, against Escherichia coli (n = 344),
      Klebsiella pneumoniae (n = 359), Enterobacter cloacae (n = 103), and Proteus
      mirabilis (n = 78). Susceptibilities of these isolates to three cephalosporins
      were assessed according to MIC breakpoints recommended by the Clinical and
      Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial
      Susceptibility Testing (EUCAST) in 2013. The double-disk synergy test using disks
      containing cefepime (30 MUg) with or without clavulanate (10 MUg) was applied to
      confirm production of ESBL for isolates with cephalosporin MIC >= 2 MUg/mL.
      RESULTS: A total of 175 isolates were verified as ESBL producers. The rates of
      cefepime susceptibility among the ESBL-producing isolates, according to CLSI
      (EUCAST) criteria, were 56.7% (22.4%) for E. coli, 61.3% (12.0%) for K.
      pneumoniae, 57.9% (31.6%) for E. cloacae, and 71.4% (7.1%) for P. mirabilis.
      Using different cefepime MIC breakpoints (MICs >= 16 MUg/mL recommended by CLSI
      criteria and >= 2 MUg/mL by EUCAST criteria) to define nonsusceptibility, we
      found that both criteria were poorer at predicting ESBL producers among K.
      pneumoniae and E. cloacae than among the other two species. In addition, we also
      found that the cefepime MIC level of 1.0 MUg/mL best distinguished non-ESBL- from
      ESBL-producing K. pneumoniae and E. cloacae. CONCLUSION: To detect ESBLs, CLSI
      should revise the cefepime MIC breakpoint against Enterobacteriaceae.

PMID- 23973411
TI  - RNA interference of a putative S-adenosyl-L-homocysteine hydrolase gene affects
      larval performance in Leptinotarsa decemlineata (Say).
AB  - In Leptinotarsa decemlineata, juvenile hormones (JHs) play primary roles in the
      regulation of metamorphosis, reproduction and diapause. In JH biosynthetic
      pathway in insect corpora allata, methylation of farnesoic acid or JH acid using
      S-adenosyl-L-methionine generates a potent feedback inhibitor S-adenosyl-L
      homocysteine (AdoHcy). Rapid removal of AdoHcy is hypothesized to be essential
      for JH synthesis. AdoHcy hydrolase (SAHase) is the only eukaryotic enzyme
      catalyzing the removal. In the present paper, we firstly cloned a putative
      LdSAHase gene from L. decemlineata. The cDNA consists of 1806 bp and encodes a
      525 amino acid protein. LdSAHase was expressed in all developmental stages. The
      gene had the highest and the lowest level of transcription respectively in the
      3rd- and 4th-instars' heads that contain corpora allata, which was positively
      correlated with JH titer in the haemolymph and the mRNA level of a JH early
      inducible gene, the Kruppel homolog 1 gene (Kr-h1). Secondly, dietary ingestion
      of bacterially-expressed LdSAHase-dsRNA significantly decreased LdSAHase and LdKr
      h1 mRNA levels, reduced JH titer, and caused the death of the larvae, and the
      failure of pupation and adult emergence. After continuous exposure for 12 days,
      42% of the larvae died, 65% of the prepupae failed to pupate and 100% of the
      pupae failed to emerge. Moreover, RNAi-mediated LdSAHase knockdown also reduced
      larval developing time, and decreased larval weight. Lastly, application of JH
      analogue pyriproxyfen to LdSAHase-dsRNA-exposed larvae did not greatly increase
      LdSAHase expression level and JH content, but up-regulated LdKr-h1 mRNA level.
      Expectedly, pyriproxyfen application could partially rescue the negative effects
      on the survival and the development. Thus, our results support the hypothesis
      that SAHase plays a critical role in JH biosynthesis in insects.

PMID- 23973412
TI  - The effect of acclimation temperature on thermal activity thresholds in polar
      terrestrial invertebrates.
AB  - In the Maritime Antarctic and High Arctic, soil microhabitat temperatures
      throughout the year typically range between -10 and +5  degrees C. However, on
      occasion, they can exceed 20  degrees C, and these instances are likely to
      increase and intensify as a result of climate warming. Remaining active under
      both cool and warm conditions is therefore important for polar terrestrial
      invertebrates if they are to forage, reproduce and maximise their fitness. In the
      current study, lower and upper thermal activity thresholds were investigated in
      the polar Collembola, Megaphorura arctica and Cryptopygus antarcticus, and the
      mite, Alaskozetes antarcticus. Specifically, the effect of acclimation on these
      traits was explored. Sub-zero activity was exhibited in all three species, at
      temperatures as low as -4.6  degrees C in A. antarcticus. At high temperatures,
      all three species had capacity for activity above 30  degrees C and were most
      active at 25  degrees C. This indicates a comparable spread of temperatures
      across which activity can occur to that seen in temperate and tropical species,
      but with the activity window shifted towards lower temperatures. In all three
      species following one month acclimation at -2  degrees C, chill coma (=the
      temperature at which movement and activity cease) and the critical thermal
      minimum (=low temperature at which coordination is no longer shown) occurred at
      lower temperatures than for individuals maintained at +4  degrees C (except for
      the CTmin of M. arctica). Individuals acclimated at +9  degrees C conversely
      showed little change in their chill coma or CTmin. A similar trend was
      demonstrated for the heat coma and critical thermal maximum (CTmax) of all
      species. Following one month at -2  degrees C, the heat coma and CTmax were
      reduced as compared with +4  degrees C reared individuals, whereas the heat coma
      and CTmax of individuals acclimated at +9  degrees C showed little adjustment.
      The data obtained suggest these invertebrates are able to take maximum advantage
      of the short growing season and have some capacity, in spite of limited
      plasticity at high temperatures, to cope with climate change.

PMID- 23973414
TI  - The epidemiology of hospice and palliative care.

PMID- 23973415
TI  - Neurogenesis along the septo-temporal axis of the hippocampus: are depression and
      the action of antidepressants region-specific?
AB  - In recent years, both major depression and antidepressant therapy have been
      linked to adult hippocampal neurogenesis. The hippocampus is not a homogeneous
      brain area, and a converging body of evidence indicates a functional dissociation
      along its septo-temporal axis, the dorsal part being involved more in
      learning/memory and spatial navigation, while the ventral sub-region is linked
      more to emotional behavior and regulation of the neuroendocrine stress axis.
      Research has therefore been conducted in an attempt to relate effects of models
      of depression and of antidepressant therapies to adult neurogenesis along the
      septo-temporal axis of the hippocampus. The present paper reviews the current
      literature addressing this question and discusses the possible mechanisms
      involved and the functional significance of such regional effects. This review
      shows that animal models of depression elicit an effect restricted to the ventral
      hippocampus more frequently than a dorsal-specific effect. However, this is also
      stage specific, and concerns neurogenesis, rather than cell proliferation or
      survival. Surprisingly, the same does not apply regarding the effects of
      selective serotonin re-uptake inhibitors that act in a more uniform way on dorsal
      and ventral adult neurogenesis in most studies. Some recently introduced clinical
      compounds (e.g., agomelatine) or putative antidepressants have a specific action
      on the ventral sub-region, indicating that an action restricted to this part of
      the brain may be sufficient to achieve remission. Finally, non-pharmacological
      manipulations that are also endowed with antidepressant effects, such as
      environmental enrichment or physical exercise, also act on both subdivisions,
      although some studies pointed to specificity of dorsal neurogenesis. The
      different treatments, acting either on the dorsal or on the ventral sub-regions,
      could promote recovery by improving either ventral- or dorsal-related functions,
      both contributing in a different way to treatment efficacy. 

PMID- 23973416
TI  - A method for estimating the effective number of loci affecting a quantitative
      character.
AB  - A likelihood method is introduced that jointly estimates the number of loci and
      the additive effect of alleles that account for the genetic variance of a
      normally distributed quantitative character in a randomly mating population. The
      method assumes that measurements of the character are available from one or both
      parents and an arbitrary number of full siblings. The method uses the fact, first
      recognized by Karl Pearson in 1904, that the variance of a character among
      offspring depends on both the parental phenotypes and on the number of loci.
      Simulations show that the method performs well provided that data from a
      sufficient number of families (on the order of thousands) are available. This
      method assumes that the loci are in Hardy-Weinberg and linkage equilibrium but
      does not assume anything about the linkage relationships. It performs equally
      well if all loci are on the same non-recombining chromosome provided they are in
      linkage equilibrium. The method can be adapted to take account of loci already
      identified as being associated with the character of interest. In that case, the
      method estimates the number of loci not already known to affect the character.
      The method applied to measurements of crown-rump length in 281 family trios in a
      captive colony of African green monkeys (Chlorocebus aethiopus sabaeus) estimates
      the number of loci to be 112 and the additive effect to be 0.26 cm. A parametric
      bootstrap analysis shows that a rough confidence interval has a lower bound of 14
      loci. 

PMID- 23973417
TI  - Attitudes and knowledge about obstructive sleep apnea among Latin American
      primary care physicians.
AB  - OBJECTIVES: We aimed to evaluate Latin American primary care physicians'
      knowledge and attitudes about obstructive sleep apnea (OSA) using a Spanish
      language version of the OSA Knowledge and Attitudes (OSAKA) questionnaire and to
      evaluate its psychometric properties. METHODS: We used a cross-sectional survey
      of general practice physicians in Ecuador, Peru, and Venezuela who completed the
      Spanish-language version OSAKA questionnaire. RESULTS: Of 684 primary care
      physicians surveyed, 367 (65%) responded (mean age, 45 years; range, 21-75
      years). Mean total knowledge (proportion of 18 items correctly answered) was 60%
      (range, 0-100%). Less than half of physicians correctly answered the questions
      about the association between OSA and hypertension. We found no significant
      differences in overall knowledge in gender or time since graduation (< or =5
      years vs. >5 years). Although 73.5% of the physicians felt confident in
      identifying patients at risk for OSA, only 35.4% felt confident in managing those
      patients and 22.1% felt confident in managing patients with continuous positive
      airway pressure (CPAP) therapy. The Spanish-language version of the OSAKA
      questionnaire had comparable psychometric properties to the English-language
      version. CONCLUSIONS: This Spanish-language version of the OSAKA yielded
      considerable variance in Spanish-speaking physicians' knowledge about OSA and
      confidence in identifying and managing patients with OSA. Focused OSA education
      for Latin American general physicians is needed.

PMID- 23973418
TI  - Safety and impact on diagnostic accuracy of early analgesia in suspected acute
      appendicitis: a meta-analysis.
AB  - BACKGROUND: The safety of early analgesia in patients suspected to have acute
      appendicitis (AA) is still controversial. METHODS: Double blind randomized
      clinical trials comparing patients receiving or not receiving opiates for early
      analgesia in suspected AA were selected for meta-analysis according to PRISMA
      guidelines. Primary outcomes were the number of patients with AA confirmed by
      histology and the number of patients undergoing surgical intervention. Secondary
      outcomes were missed diagnoses, false positive AA and complication rate. Effect
      sizes were calculated using a Mantel-Haenszel fixed effects model. RESULTS:
      Previously published papers mostly analyzed surrogate end-points such as
      physician's confidence about the diagnosis or the alteration of clinical signs,
      subjective parameters dependent on personal perception. Our article focused on
      clinical outcome and specifically investigated those potentially related to AA
      instead of unspecified abdominal pain. Opiate administration did not have an
      impact on the number of histologically proven AA (OR = 1.196 [0.875-1.635]; P =
      0.261). Differences in appendectomy rates were only slightly above the threshold
      for statistical significance (OR = 1.350 [0.966-1.887]; P = 0.079), suggesting
      that analgesia might influence the treatment approach. On the other hand missed
      diagnoses (OR = 0.509 [0.087-2.990]; P = 0.455) and false positive AA (OR = 1.071
      [0.596-1.923]; P = 0.818) ascertained by histologic examination were unaffected,
      so diagnostic accuracy was retained. Safety was not compromised by opiates, as
      the difference in complication rates did not reach statistical significance (OR =
      0.615 [0.217-1.748]; P = 0.372). CONCLUSION: Early analgesia with opiates in
      suspected AA might influence the approach to treatment, but does not appear to
      alter diagnostic accuracy or surgical outcome. To support our findings, further
      trials on larger sample sizes from different age groups and both genders are
      needed.

PMID- 23973419
TI  - Unrelated strain methicillin-resistant Staphylococcus aureus colonization of
      health care workers in a neonatal intensive care unit: findings of an outbreak
      investigation.
AB  - Three neonates and 5 health care workers were identified as colonized with
      methicillin-resistant Staphylococcus aureus (MRSA) out of 222 individuals
      screened during an outbreak investigation in an 18-bed neonatal intensive care
      unit. Two of 3 MRSA neonatal isolates demonstrated identical pulsed-field gel
      electrophoresis clonal patterns but no clonal association was found among
      isolates from the 5 employees or between employees and neonates. Increased MRSA
      unrelated strain colonization among health care workers supports increased MRSA
      community prevalence and probable decreased utility of mass screening. 

PMID- 23973420
TI  - Seasonal variation in health care-associated bloodstream infection: increase in
      the incidence of gram-negative bacteremia in nonhospitalized patients during
      summer.
AB  - OBJECTIVE: Recent research has suggested that episodes of gram-negative (GN)
      bloodstream infection (BSI) are more common in the population during summer
      months. Our objective was to determine if the same phenomenon could be observed
      in patients with health care-associated (HCA) BSI, and if so, whether a summer
      peak was less apparent in patients accommodated in a climate-controlled hospital
      environment. METHODS: Data from episodes of HCA BSI spanning an 11-year period
      were analyzed. To test for seasonal variation in HCA BSI among hospitalized and
      nonhospitalized patients, and between GN and gram-positive organisms, the chi(2)
      goodness-of-fit test was used. RESULTS: There were 440 episodes of HCA GN BSI of
      which 259 (59%) occurred in inpatients and 181 (41%) occurred in noninpatients. A
      significant increase in the frequency of HCA GN BSI was observed in
      nonhospitalized patients during the summer months (P = .03) but not in climate
      controlled hospitalized patients. The most common source of infection in these
      patents was an intravascular device (38%). CONCLUSIONS: We found an increased
      incidence of GN HCA BSI during summer that was not apparent in our inpatient
      cohort. The cause is unknown. It might be prudent to advise patients at risk of
      BSI (eg, those receiving intravascular infusions) to minimize exposure to high
      environmental temperature and to educate on possible behavioral factors that may
      increase risk.

PMID- 23973421
TI  - Community-based infections and the potential role of common touch surfaces as
      vectors for the transmission of infectious agents in home and community settings.
AB  - Community-based pathogens that can survive on common touch surfaces include those
      that can cause gastrointestinal, respiratory, and skin infections. Our hands play
      an obvious role in the transmission of many of these pathogens, but common touch
      surfaces are also part of the transmission equation. Traditionally, common touch
      surfaces have not been the main focus of cleaning and sanitation in household and
      community settings. Infectious disease continues to be of concern globally due in
      part to emergence of new pathogens, antibiotic-resistant organisms, and a growing
      immunocompromised community. As a result, it is important to prevent and minimize
      the infection risk in homes and in the community. Understanding the role of
      common touch surfaces should inform surface hygiene practices and these surfaces
      should be the subject of future intervention studies. 

PMID- 23973422
TI  - Comparison of central line-associated bloodstream infection rates when changing
      to a zero fluid displacement intravenous needleless connector in acute care
      settings.
AB  - This was a multicenter, quasiexperimental, 140-month, acute care study comparing
      central line-associated bloodstream infection rates associated with positive or
      negative intravenous connectors to a zero fluid displacement connector. A
      decrease in central line-associated bloodstream infections was found after
      changing from either negative or positive intravenous connectors to the zero
      fluid displacement connector (P = .004) with total cost savings of over $3
      million.

PMID- 23973423
TI  - A multicenter study using positive deviance for improving hand hygiene
      compliance.
AB  - BACKGROUND: Positive deviance (PD) can be a strategy for the improvement of hand
      hygiene (HH) compliance. METHODS: This study was conducted in 8 intensive care
      units and 1 ward at 7 tertiary care, private, and public hospitals. Phase 1 was a
      3-month baseline period (from August to October 2011) in which HH counts were
      performed by observers using iPods (iScrub program). From November 2011 to July
      2012, phase 2, a PD intervention was performed in all the participating centers.
      We evaluated the consumption of HH products (alcohol gel and chlorhexidine) and
      the incidence density of health care-associated infections. RESULTS: There was a
      total of 5,791 HH observations in the preintervention phase and 11,724 HH
      observations in the intervention phase (PD). A statistically significant
      difference was found in overall HH compliance with 46.5% in the preintervention
      phase and 62.0% in the PD phase (P < .001). There was a statistically significant
      reduction in the incidence of density of device-associated infections per 1,000
      patient-days and also in the median of length of stay between the preintervention
      phase and the PD phase (13.2 vs 7.5 per 1,000 patient-days, respectively, P =
      .039; and 11.0 vs 6.8 days, respectively, P < .001, respectively). CONCLUSION: PD
      demonstrated great promise for improving HH in multiple inpatient settings and
      was associated with a decrease in the median length of stay and the incidence of
      device-associated HAIs.

PMID- 23973424
TI  - Risk of methicillin-resistant Staphylococcus aureus surgical site infection in
      patients with nasal MRSA colonization.
AB  - BACKGROUND: Patients colonized with methicillin-resistant Staphylococcus aureus
      (MRSA) are at increased risk for invasive infection compared with noncolonized
      patients; however, the magnitude of risk for MRSA surgical site infection (SSI)
      is unclear. To aid in planning of infection prevention strategies, we sought to
      assess the incidence of MRSA SSI in MRSA carriers. METHODS: We conducted a
      retrospective cohort study at our tertiary care center of inpatients who
      underwent MRSA polymerase chain reaction (PCR) screen of the nares within 30 days
      before a National Healthcare Safety Network principal procedure between April
      2008 and July 2010. RESULTS: The rate of MRSA SSI was 1.86% in the MRSA PCR
      positive group (n = 431) and 0.20% in the MRSA PCR-negative group (n = 9432).
      Multivariate analysis identified MRSA PCR-positive status as an independent risk
      factor for MRSA SSI (odds ratio, 9.20; 95% confidence interval, 3.81-20.47; P <
      .0001); other risk factors included duration of surgery >=137 minutes, American
      Society of Anesthesiologists score >=3, and abdominal surgery. CONCLUSIONS:
      Surgical patients with a positive nasal MRSA PCR screen had a 9-fold greater odds
      of developing a subsequent MRSA SSI compared with patients with a negative nasal
      MRSA PCR screen. The incidence of MRSA SSI in PCR-positive patients was low
      (1.86%), however, and identifying subsets of patients at greatest risk for SSI
      may help target decolonization and other interventions.

PMID- 23973425
TI  - Immunizing health care workers against influenza: a glimpse into the challenges
      with voluntary programs and considerations for mandatory policies.
AB  - BACKGROUND: Vaccination of health care workers (HCWs) is an important patient
      safety initiative. It prevents influenza infection among patients and reduces
      staff illness and absenteeism. Despite these benefits, HCW influenza immunization
      uptake is low. Therefore, strategies to achieve high immunization coverage in
      HCWs, barriers to uptake, and perceptions of mandatory influenza immunization
      policies were discussed in key informant interviews with influenza immunization
      program planners. METHODS: We conducted telephone interviews with 23 influenza
      immunization program planners from 21 organizations (7 acute care hospitals, 6
      continuing care facilities, and 8 public health organizations) across Canada. We
      used content analysis to identify themes from the interviews. RESULTS:
      Participants used a variety of promotional and educational activities, and many
      vaccine delivery approaches, to support HCW immunization programs. Barriers to
      achieving high coverage in HCWs included misconceptions about the safety and
      effectiveness of the influenza vaccine, negative personal experiences associated
      with the vaccine, and antivaccine sentiments. Participants mentioned mandatory
      influenza immunizations as a solution to low coverage. However, they identified
      challenges with this approach such as obtaining support from stakeholders,
      enforcement, and limiting personal autonomy. CONCLUSION: Participants believed
      immunization coverage in health care organizations will continue to be suboptimal
      using existing program strategies. Although participants discussed mandatory
      immunization as a way to improve uptake, potential obstacles will need to be
      addressed for this to be implemented successfully.

PMID- 23973426
TI  - Clonally related Burkholderia contaminans among ventilated patients without
      cystic fibrosis.
AB  - We investigated a cluster of 10 Burkholderia cepacia complex-positive cultures
      among ventilated patients and those with a tracheostomy in an acute care
      hospital. Isolates from 5 patients had outbreak-strain-related Burkholderia
      contaminans. Isolates of B. cepacia complex unrelated to the outbreak strain were
      cultured from a sink drain. The investigation identified practices that might
      have led to contamination of patient respiratory care supplies with tap water,
      which might have contributed to the cluster.

PMID- 23973428
TI  - A luminol chemiluminescence method for sensing histidine and lysine using enzyme
      reactions.
AB  - The analysis of free amino acids in urine and plasma is useful for estimating
      disease status in clinical diagnoses. Changes in the concentration of free amino
      acids in foods are also useful markers of freshness, nutrition, and taste. In
      this study, the specific interaction between aminoacyl-tRNA synthetase (aaRS) and
      its corresponding amino acid was used to measure amino acid concentrations.
      Pyrophosphate released by the amino acid-aaRS binding reaction was detected by
      luminol chemiluminescence; the method provided selective quantitation of 1.0-30
      MUM histidine and 1.0-60 MUM lysine.

PMID- 23973427
TI  - Consequences of chondrocyte hypertrophy on osteoarthritic cartilage: potential
      effect on angiogenesis.
AB  - OBJECTIVE: The aim of this study was to investigate the link between the
      hypertrophic phenotype of chondrocytes and angiogenesis in osteoarthritis (OA)
      and more particularly to demonstrate that OA hypertrophic chondrocytes
      potentially express a phenotype promoting angiogenesis through the expression of
      factors controlling endothelial cells migration, invasion and adhesion. METHOD:
      Human OA chondrocytes were cultivated in alginate beads in medium supplemented
      with 10% fetal bovine serum (FBS) to induce chondrocyte hypertrophy. The
      hypertrophic phenotype was characterized throughout 28 days of culture by
      measuring the expression of specific genes and by a microscopic observation of
      cellular morphology. The effect of media conditioned by OA hypertrophic
      chondrocyte on endothelial cells migration, invasion and adhesion was evaluated
      in functional assays. Moreover, hypertrophic OA chondrocytes were tested for the
      expression of angiogenic factors by real-time RT-PCR. RESULTS: Specific markers
      of hypertrophy and observation of cellular morphology attested of the
      hypertrophic phenotype of chondrocytes in our culture model. Functional
      angiogenesis assays showed that factors produced by hypertrophic chondrocytes
      stimulated migration, invasion and adhesion of endothelial cells. Among the
      evaluated angiogenic factors, bone sialoprotein (BSP) was the most highly
      upregulated in hypertrophic chondrocytes. The inhibition of endothelial cell
      adhesion by a GRGDS peptide confirmed the implication of RGD domain proteins,
      like BSP, in hypertrophic chondrocyte-induced adhesion of endothelial cells.
      CONCLUSION: Hypertrophic differentiation of chondrocyte may promote angiogenesis.
      Our findings established the relation of BSP with OA chondrocyte hypertrophy and
      suggested that this factor could constitute a potential target to control
      cartilage neovascularisation in OA.

PMID- 23973429
TI  - Eleven-year experience on anti-TB drugs direct susceptibility testing from
      Siriraj Hospital, Thailand.
AB  - The early detection of drug-resistant tuberculosis (TB) strains is of utmost
      importance for patient management and effective TB control programs. This study
      aimed to demonstrate the performance of direct drug susceptibility testing (DST)
      performed in our laboratory in the past 11 years. The direct DST was performed on
      Middlebrook 7H10 medium using isoniazid (INH) and rifampicin (RIF), and the
      results were compared with those obtained from indirect DST (gold standard). The
      direct DST was performed with 15,598 smear-positive sputum samples, of which
      11,284 (72%) yielded reportable results. Sensitivity, specificity, positive
      predictive value, and negative predictive value were calculated and revealed 89%,
      99%, 95%, and 99%, respectively, for RIF and 90%, 98%, 93%, and 97%,
      respectively, for INH. Direct DST results could be reported within 1 month after
      sample processing. This method was also shown to be suitable for use in resource
      limited countries, particularly in settings with high numbers of TB cases. 

PMID- 23973430
TI  - The validity of cerebrospinal fluid parameters for the diagnosis of tuberculous
      meningitis.
AB  - OBJECTIVES: To assess the diagnostic validity of laboratory cerebrospinal fluid
      (CSF) parameters for discriminating between tuberculous meningitis (TBM) and
      other causes of meningeal syndrome in high tuberculosis incidence settings.
      METHODS: From November 2009 to November 2011, we included patients with a
      clinical suspicion of meningitis attending two hospitals in Lima, Peru. Using a
      composite reference standard, we classified them as definite TBM, probable TBM,
      and non-TBM cases. We assessed the validity of four CSF parameters, in isolation
      and in different combinations, for diagnosing TBM: adenosine deaminase activity
      (ADA), protein level, glucose level, and lymphocytic pleocytosis. RESULTS: One
      hundred and fifty-seven patients were included; 59 had a final diagnosis of TBM
      (18 confirmed and 41 probable). ADA was the best performing parameter. It
      attained a specificity of 95%, a positive likelihood ratio of 10.7, and an area
      under the receiver operating characteristics curve of 82.1%, but had a low
      sensitivity (55%). None of the combinations of CSF parameters achieved a fair
      performance for 'ruling out' TBM. CONCLUSIONS: Finding CSF ADA greater than 6 U/l
      in patients with a meningeal syndrome strongly supports a diagnosis of TBM and
      permits the commencement of anti-tuberculous treatment.

PMID- 23973432
TI  - Treatment of a relapse-remitting model of multiple sclerosis with opioid growth
      factor.
AB  - Relapse-remitting multiple sclerosis (MS) is an immune-mediated disease of the
      central nervous system that affects more than 2.5 million individuals worldwide.
      While the etiology of MS is unclear, disease manifestation involves proliferation
      and activation of lymphocytes and astrocytes, leading to demyelination and
      neuronal damage. Current therapies are not completely effective, and few target
      the underlying pathophysiology of MS. The purpose of this study was to examine
      the therapeutic efficacy of a novel biological pathway, the opioid growth factor
      (OGF)-OGF receptor (OGFr) axis. OGF inhibits DNA synthesis and has been shown to
      repress proliferation of T lymphocytes, microglia, and astrocytes in other
      autoimmune disorders. An animal model for relapse-remitting experimental
      autoimmune encephalomyelitis (RR-EAE) was established by immunization of SJL/J
      mice with proteolipid protein. Treatment with OGF or saline was initiated
      simultaneously with immunization, and within 9 days, behavioral signs of RR-EAE
      were observed. OGF-treated RR-EAE animals had less severe clinical disease than
      mice receiving saline and exhibited 66% reductions in median cumulative disease
      scores, as well as prolonged periods of remission and diminished number and
      length of disease relapses. Neuropathological examination of lumbar spinal cord
      revealed reductions in the number of T lymphocytes, microglia/macrophages, and
      activated astrocytes, with cell proliferation being the mechanism targeted by
      OGF. Areas of demyelination and neuronal damage were markedly reduced during the
      55-day observation period. These data are the first to demonstrate that OGF
      prevented relapses in RR-EAE and diminished underlying neuropathology,
      corroborating the potential of the OGF-OGF receptor pathway for treatment of MS. 

PMID- 23973431
TI  - Knockout of vascular early response gene worsens chronic stroke outcomes in
      neonatal mice.
AB  - Vascular early response gene (Verge) is a novel immediate early gene that is
      highly expressed during developmental angiogenesis and after ischemic insults in
      adult brain. However, the role of Verge after neonatal injury is not known. In
      the present study, we investigated the hypothesis that Verge contributes to
      vascular remodeling and tissue repair after neonatal ischemic injury. The Rice
      Vanucci model (RVM) was employed to induce neonatal stroke in both Verge knockout
      (KO) and wild-type (WT) postnatal day 10 (P10) mice. Histological and behavioral
      outcomes at acute (24h), subacute (7 days) and chronic (30 days) phases were
      evaluated. Angiogenesis, neurogenesis, and glial scar formation were also
      examined in the ischemic brain. No significant differences in outcomes were found
      between WT and Verge mice at 24h or 7 days after stroke. However genetic deletion
      of Verge led to pronounced cystic cavitation, decreased angiogenensis and glial
      scar formation in the ischemic hemisphere compared to WT mice at 30 days. Verge
      KO mice also had significantly worse functional outcomes at 30 days which was
      accompanied by decreased neurogenesis and angiogenesis in the ischemic
      hemisphere. Our study suggests that Verge plays an important role in the
      induction of neurogenesis and angiogenesis after ischemia, contributes to
      improved tissue repair, and enhances chronic functional recovery. 

PMID- 23973433
TI  - Modified oleic cottonseeds show altered content, composition and tissue-specific
      distribution of triacylglycerol molecular species.
AB  - Targeted increases in monounsaturated (oleic acid) fatty acid content of refined
      cottonseed oil could support improved human nutrition and cardiovascular health.
      Genetic modifications of cottonseed fatty acid composition have been accomplished
      using several different molecular strategies. Modification of oleic acid content
      in cottonseed embryos using a dominant-negative protein approach, while
      successful in effecting change in the desired fatty acid composition, resulted in
      reduced oil content and seed viability. Here these changes in fatty acid
      composition were associated with changes in dominant molecular species of
      triacylglycerols (TAGs) and their spatial distributions within embryo tissues. A
      combination of mass spectrometry (MS)-based lipidomics approaches, including MS
      imaging of seed cryo-sections, revealed that cotton embryos expressing a non
      functional allele of a Brassica napus delta-12 desaturase showed altered
      accumulation of TAG species, especially within cotyledonary tissues. While lipid
      analysis of seed extracts could demonstrate detailed quantitative changes in TAG
      species in transgenics, the spatial contribution of metabolite compartmentation
      could only be visualized by MS imaging. Our results suggest tissue-specific
      differences in TAG biosynthetic pathways within cotton embryos, and indicate the
      importance of considering the location of metabolites in tissues in addition to
      their identification and quantification when developing a detailed view of
      cellular metabolism. 

PMID- 23973434
TI  - Identification of a vaccine against schistosomiasis using bioinformatics and
      molecular modeling tools.
AB  - Schistosomiasis is a serious public health problem in Brazil and worldwide.
      Although the drugs used to treatment schistosomiasis are effective, the disease
      continues to expand in all endemic countries due to constant reinfection, poor
      sanitation, and the lack of effective programs for disease control. However,
      advances generated through genome projects have provided important information
      that has improved the understanding of the biology of this parasite. These
      advances, associated with the advent of bioinformatic analysis, are becoming an
      important tool in reverse vaccinology. Through database access to the DNA and
      protein sequences of Schistosoma mansoni and the use of bioinformatics programs,
      fourteen epitopes were identified. Five epitopes were obtained from proteins
      whose immunogenic potential had already been assessed in other studies (KP), and
      nine whose immunogenic potential is unknown (UP). To improve stimulation of the
      host immune system, the selected epitopes were modeled with a sugar moiety. After
      this addition, all of the epitopes showed structures similar to those observed in
      the native proteins, but only eleven of the peptides presented thermodynamically
      stable structures. Prediction analysis and molecular modeling showed that the
      glycopeptides presented here are important targets in the search for a vaccine
      against schistosomiasis. Additionally, they suggest that these molecules may be
      used in immunological assays to evaluate the level of protection, the effect on
      pathology reduction and the profile of cytokines and antibodies induced by them. 

PMID- 23973436
TI  - Sex steroid modulation of sensory processing.

PMID- 23973435
TI  - Slow conformational changes in MutS and DNA direct ordered transitions between
      mismatch search, recognition and signaling of DNA repair.
AB  - MutS functions in mismatch repair (MMR) to scan DNA for errors, identify a target
      site and trigger subsequent events in the pathway leading to error removal and
      DNA re-synthesis. These actions, enabled by the ATPase activity of MutS, are now
      beginning to be analyzed from the perspective of the protein itself. This study
      provides the first ensemble transient kinetic data on MutS conformational
      dynamics as it works with DNA and ATP in MMR. Using a combination of fluorescence
      probes (on Thermus aquaticus MutS and DNA) and signals (intensity, anisotropy and
      resonance energy transfer), we have monitored the timing of key conformational
      changes in MutS that are coupled to mismatch binding and recognition, ATP binding
      and hydrolysis, as well as sliding clamp formation and signaling of repair.
      Significant findings include (a) a slow step that follows weak initial
      interaction between MutS and DNA, in which concerted conformational changes in
      both macromolecules control mismatch recognition, and (b) rapid, binary switching
      of MutS conformations that is concerted with ATP binding and hydrolysis and (c)
      is stalled after mismatch recognition to control formation of the ATP-bound MutS
      sliding clamp. These rate-limiting pre- and post-mismatch recognition events
      outline the mechanism of action of MutS on DNA during initiation of MMR. 

PMID- 23973437
TI  - Suppression of thioredoxin system contributes to silica-induced oxidative stress
      and pulmonary fibrogenesis in rats.
AB  - Silicosis is one of the most prevalent occupational lung diseases worldwide. This
      study aimed to investigate the possible mechanism that silica affected
      thioredoxin (Trx) system during the development of silicosis in vivo. Male Wistar
      rats were randomly divided into saline group and silica group in which rats were
      intratracheally instilled with a single dose of silica suspension (50mg in 1ml
      saline/rat). After 7, 15 or 30 days instillation, rats were sacrificed.
      Biochemical parameters and histopathology were assessed. Our results demonstrated
      that silica could significantly cause the accumulation of reactive oxygen species
      (ROS) and malondialdehyde (MDA) as well as activate antioxidative protein Nuclear
      factor erythroid 2-related factor 2 (Nrf2) and its downstream protein Trx in the
      early exposure to silica. The inhibition of Trx activity and the down-regulated
      expression of thioredoxin reductase (TrxR), suggesting that the function of Trx
      system may be suppressive induced by silica. Content of lung hydroxyproline and
      histopathological results showed significant fibrosis development with time. In
      conclusion, our study demonstrated that silica could suppress the Trx system to
      perturb the redox balance, elicit oxidative stress, and eventually induce
      pulmonary fibrosis. 

PMID- 23973439
TI  - Eye rivalry and object rivalry in the intact and split-brain.
AB  - Both the eye of origin and the images themselves have been found to rival during
      binocular rivalry. We presented traditional binocular rivalry stimuli (face to
      one eye, house to the other) and Diaz-Caneja stimuli (half of each image to each
      eye) centrally to both a split-brain participant and a control group. With
      traditional rivalry stimuli both the split-brain participant and age-matched
      controls perceived more coherent percepts (synchronised across the hemifields)
      than non-synchrony, but our split-brain participant perceived more non-synchrony
      than our controls. For rival stimuli in the Diaz-Caneja presentation condition,
      object rivalry gave way to eye rivalry with all participants reporting more non
      synchrony than coherent percepts. We have shown that splitting the stimuli across
      the hemifields between the eyes leads to greater eye than object rivalry, but
      that when traditional rival stimuli are split as the result of the severed corpus
      callosum, traditional rivalry persists but to a lesser extent than in the intact
      brain. These results suggest that communication between the early visual areas is
      not essential for synchrony in traditional rivalry stimuli, and that other routes
      for interhemispheric interactions such as subcortical connections may mediate
      rivalry in a traditional binocular rivalry condition. 

PMID- 23973440
TI  - Focal cone ERGs of rhodopsin Pro347Leu transgenic rabbits.
AB  - A rhodopsin P347L transgenic (Tg) rabbit, a model of retinitis pigmentosa, has
      been generated in our laboratory. The purpose of this study was to determine the
      properties of focal areas of the retina in this rabbit model during the course of
      retinal degeneration. To accomplish this, we recorded focal ERGs from wild-type
      (WT) and Tg rabbits at ages 3, 6, and 12 months. A 15 degrees  stimulus spot was
      used to elicit the focal ERGs from the center of the visual streak and from four
      surrounding areas. We found that the amplitudes of the focal cone ERG b-waves and
      oscillatory potentials (OPs) of the Tg rabbits in the five areas decreased
      progressively with increasing age and became almost non-recordable at 12 months.
      There were no significant regional differences in the b-waves of Tg rabbits
      recorded from the 5 areas. The amplitudes of the OPs were better preserved than
      the b-waves and the OPs/b-wave ratio was higher than that in WT rabbits at every
      recording area. The summed OPs amplitudes, which most likely originate from the
      amacrine and/or ganglion cells, recorded from the area superior to the optic disc
      was significantly larger than that from other areas at 3- and 6-months-old. This
      indicated that the inner retinal neurons were not altered equally after
      photoreceptor degeneration in this rabbit model.

PMID- 23973438
TI  - Computer-aided identification of novel protein targets of bisphenol A.
AB  - The xenoestrogen bisphenol A (2,2-bis-(p-hydroxyphenyl)-2-propane, BPA) is a
      known endocrine-disrupting chemical used in the fabrication of plastics, resins
      and flame retardants, that can be found throughout the environment and in
      numerous every day products. Human exposure to this chemical is extensive and
      generally occurs via oral route because it leaches from the food and beverage
      containers that contain it. Although most of the effects related to BPA exposure
      have been linked to the activation of the estrogen receptor (ER), the mechanisms
      of the interaction of BPA with protein targets different from ER are still
      unknown. Therefore, the objective of this work was to use a bioinformatics
      approach to identify possible new targets for BPA. Docking studies were performed
      between the optimized structure of BPA and 271 proteins related to different
      biochemical processes, as selected by text-mining. Refinement docking experiments
      and conformational analyses were carried out using LigandScout 3.0 for the
      proteins selected through the affinity ranking (lower than -8.0kcal/mol). Several
      proteins including ERR gamma (-9.9kcal/mol), and dual specificity protein kinases
      CLK-4 (-9.5kcal/mol), CLK-1 (-9.1kcal/mol) and CLK-2 (-9.0kcal/mol) presented
      great in silico binding affinities for BPA. The interactions between those
      proteins and BPA were mostly hydrophobic with the presence of some hydrogen bonds
      formed by leucine and asparagine residues. Therefore, this study suggests that
      this endocrine disruptor may have other targets different from the ER. 

PMID- 23973441
TI  - UBQLN2 mutations are not a frequent cause of amyotrophic lateral sclerosis in
      Ireland.
AB  - Mutations in UBQLN2 have been shown to be a cause of dominant X-linked
      amyotrophic lateral sclerosis (ALS). Occurrences of mutations in this gene vary
      across ALS populations. We screened UBQLN2 for mutations in a final cohort of 150
      Irish ALS patients. Individuals who were from families with male-to-male
      transmission or who carried pathogenic hexanucleotide repeat expansions in
      C9orf72 were excluded. Apart from common synonymous variation, no sequence
      variants in UBQLN2 were observed. Mutations in UBQLN2 are therefore not a
      frequent cause of ALS in the Irish population. 

PMID- 23973442
TI  - Klotho upregulation contributes to the neuroprotection of ligustilide in an
      Alzheimer's disease mouse model.
AB  - Klotho, an aging-suppressor gene, encodes a protein that potentially acts as a
      neuroprotective factor by modulating insulin-like growth factor 1 signaling and
      oxidative stress. In the present study, we investigated the potential role of
      Klotho in the therapeutic effect of ligustilide against Alzheimer's disease (AD)
      like neuropathologies and memory impairment in aged senescence-accelerated mouse
      prone-8 (SAMP8) mice. Ligustilide treatment (10 and 40 mg/kg for 8 weeks,
      intragastrically) in 10-month-old SAMP8 mice reduced memory deficits, amyloid
      beta(1)-42 accumulation, tau phosphorylation, and neuron loss, increased
      mitochondrial manganese-superoxide dismutase and catalase expression and
      activity, and decreased malondialdehyde, protein carbonyl, and 8
      hydroxydesoxyguanosine levels in the brain. Ligustilide upregulated Klotho
      expression in the cerebral choroid plexus and serum, decreased Akt and Forkhead
      box class O1 phosphorylation. Moreover, ligustilide inhibited the insulin-like
      growth factor 1 pathway and induced Forkhead box class O1 activation in 293T
      cells along with Klotho upregulation. An inverse correlation was found between
      Klotho expression and the AD phenotype, suggesting that Klotho might be a novel
      therapeutic target for age-related AD, and Klotho upregulation might contribute
      to the neuroprotective effect of ligustilide against AD.

PMID- 23973443
TI  - Association of internet use and depression among the spinal cord injury
      population.
AB  - OBJECTIVE: To examine the relation between the frequency of Internet use and
      depression among people with spinal cord injury (SCI). DESIGN: Cross-sectional
      survey. SETTING: SCI Model Systems. PARTICIPANTS: People with SCI (N=4618) who
      were interviewed between 2004 and 2010. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: The frequency of Internet use and the severity of depressive
      symptoms were measured simultaneously by interview. Internet use was reported as
      daily, weekly, monthly, or none. The depressive symptoms were measured by the
      Patient Health Questionnaire-9 (PHQ-9), with 2 published criteria being used to
      screen for depressive disorder. The diagnostic method places more weight on
      nonsomatic items (ie, items 1, 2, and 9), and the cut-off method that determines
      depression by a (PHQ-9) score >=10 places more weight on somatic factors. The
      average scores of somatic and nonsomatic items represented the severity of
      somatic and nonsomatic symptoms, respectively. RESULTS: Our multivariate logistic
      regression model indicated that daily Internet users were less likely to have
      depressive symptoms (odds ratio=.77; 95% confidence interval, .64-.93), if the
      diagnostic method was used. The linear multivariate regression analysis indicated
      that daily and weekly Internet usage were associated with fewer nonsomatic
      symptoms; no significant association was observed between daily or weekly
      Internet usage and somatic symptoms. CONCLUSIONS: People with SCI who used the
      Internet daily were less likely to have depressive symptoms.

PMID- 23973444
TI  - Altering electromyography studies: importance of the electromyographer's
      perception of patient pain.
AB  - OBJECTIVE: To determine the relation between the patient's actual pain, the
      electromyographer's perception of patient pain, and whether an electromyogram
      (EMG) is altered. DESIGN: Patients undergoing electromyography reported expected
      pain and procedure-related overall pain on a 100-mm visual analog scale (VAS).
      Blinded electromyographers estimated patient pain levels and indicated if they
      altered the study in any way because of this perception. Multivariable logistic
      regression was used to determine predictors of altering the EMG. Paired t tests
      were used to compare overall pain with expected pain and electromyographer
      perception of pain. SETTING: Tertiary referral center. PARTICIPANTS: Referred
      sample of adult subjects (N=304). INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Patient pain, electromyographer perception of patient pain, and whether
      an EMG was altered because of the electromyographer's perception of patient pain.
      RESULTS: Mean VAS scores +/- SD were 48+/-25mm for patient-expected pain
      (P<.001), 42+/-24mm for electromyographer perception of pain (P<.0001), and 36+/
      25mm for actual overall pain. Electromyographers altered their study 31.7% of the
      time because of concerns about pain. For every 13-mm increase on the VAS (a
      prespecified clinically meaningful difference), the electromyographer perception
      of pain increased the odds of altering a study 2.36 times (95% confidence
      interval [CI], 1.71-3.26), whereas patient overall pain did not have a
      significant effect (odds ratio=1.12; 95% CI, .86-1.47). CONCLUSIONS: Patients
      expect EMGs to be more painful than they are. Electromyographers overestimate
      patient pain and are more likely to alter their studies when they believe
      patients are experiencing more pain, independently of whether patients actually
      have more pain. Improving the communication between electromyographers and
      patients may prevent unnecessary alterations.

PMID- 23973445
TI  - Which neuromuscular attributes are most associated with mobility among older
      primary care patients?
AB  - OBJECTIVE: To identify the neuromuscular attributes that are associated with self
      reported mobility status among older primary care patients. DESIGN: Cohort study.
      SETTING: Metropolitan-based health care system. PARTICIPANTS: Community-dwelling
      primary care patients aged >=65 years (N=430), with self-reported modification of
      mobility tasks resulting from underlying health conditions. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Basic and Advanced Lower Extremity Function as
      measured by the Late Life Function and Disability Instrument. RESULTS: We
      constructed multivariable linear regression models evaluating both outcomes. For
      Basic Lower Extremity Function, leg strength, leg velocity, trunk extensor muscle
      endurance, and ankle range of motion (ROM) were statistically significant
      predictors (P<.001, R(2)=.21). For Advanced Lower Extremity Function, leg
      strength, leg strength asymmetry, leg velocity, trunk extensor muscle endurance,
      and knee flexion ROM were statistically significant predictors (P<.001,
      R(2)=.39). Sensitivity analyses conducted using multiple imputations to account
      for missing data confirmed these findings. CONCLUSIONS: This analysis highlights
      the relevance and importance of 5 categories of neuromuscular attributes:
      strength, speed of movement, ROM, asymmetry, and trunk stability. It identifies
      novel attributes (leg velocity and trunk extensor muscle endurance) relevant to
      mobility and highlights that impairment profiles vary by the level of mobility
      assessed. These findings will inform the design of more thorough and potentially
      more effective disability prevention strategies.

PMID- 23973446
TI  - Possible mechanisms of neutrophil activation in Behcet's disease.
AB  - Behcet's disease (BD) is a systemic inflammatory disorder characterized by
      recurrent episodes of acute inflammation consisting mainly of neutrophil
      infiltration around blood vessels in affected tissues. BD probably occurs due to
      neutrophil-based innate immune responses orchestrated by a complex interplay
      among gamma-delta T lymphocytes, natural killer T cells, monocytes and Th17
      lymphocytes in which type-I interferon is possibly a key element for inflammatory
      downregulation. However, strong evidence is still scarce. This article compiles
      the literature in an attempt to summarize the possible mechanisms by which
      neutrophils are activated in BD and suggests directions for future research. 

PMID- 23973447
TI  - Egr-1 increases in the prefrontal cortex following training in the context
      preexposure facilitation effect (CPFE) paradigm.
AB  - The context pre-exposure facilitation effect (CPFE) is a modified form of
      standard contextual fear conditioning that dissociates learning about the context
      during a preexposure phase from learning the context-shock association during an
      immediate shock training phase conducted on separate days. Fear conditioning in
      the CPFE is an associative process in which only animals that are preexposed to
      the same context they are later given an immediate shock in demonstrate freezing
      when tested for conditioned fear memory. Previous research has shown that the
      hippocampus and amygdala are necessary for different phases of the CPFE, but
      whether other brain regions are also involved is unknown. The present study
      examined expression of the immediate-early gene early growth response gene 1 (Egr
      1; also called Zif268, Ngfi-a, Krox-24) in the dorsal hippocampus, lateral
      nucleus of the amygdala, retrosplenial cortex, and several prefrontal cortex
      regions (infralimbic and prelimbic medial prefrontal cortex, anterior cingulate,
      and orbitofrontal cortex) following each phase of the CPFE in juvenile rats.
      Animals preexposed to the conditioning context displayed fear conditioned
      freezing during a retention test whereas rats preexposed to an alternate context
      did not. Following context preexposure, Egr-1 mRNA was elevated in context and
      alternate context exposed animals compared to home-cage control rats in almost
      all regions analyzed. Following the context-shock training phase, fear
      conditioned rats displayed significantly more Egr-1 mRNA expression in the
      infralimbic, prelimbic, and orbitofrontal cortices compared to the alternate
      context preexposed control rats. These differences in Egr-1 expression were not
      found in amygdala between the preexposed context and alternate context rats. No
      sex differences were observed following preexposure or training in any regions
      analyzed. The findings suggest that increased expression of Egr-1 within the
      prefrontal cortex is associated with contextual fear conditioning in the CPFE
      paradigm. 

PMID- 23973449
TI  - Cholesterol diet counteracts repeated anesthesia/infusion-induced cognitive
      deficits in male Brown Norway rats.
AB  - A variety of cardiovascular and cerebrovascular diseases are associated with
      alterations in cholesterol levels and metabolism. Moreover, convincing evidence
      shows that high cholesterol diet can lead to learning and memory impairments. On
      the other hand, a significant body of research has also demonstrated that
      learning is improved by elevated dietary cholesterol. Despite these conflicting
      findings, it is clear that cholesterol plays an important role in these cognitive
      properties. However, it remains unclear how this blood-brain barrier (BBB)
      impenetrable molecule affects the brain and under what circumstances it provides
      either detrimental or beneficial effects to learning and memory. The aim of this
      study was to characterize the effects of 5% cholesterol diet on six-month-old
      inbred Brown Norway rats. More important, we sought to examine the role that
      cholesterol can play when repeated anesthesia and intravenous infusion disrupts
      cognitive function. This present study supports previous work showing that
      enriched cholesterol diet leads to significant alterations in neuroinflammation
      and BBB disruption. Following repeated anesthesia and intravenous infusion of
      saline we observe that animals under normal diet conditions exhibit significant
      deficiencies in spatial learning and cholinergic neuron populations compared to
      animals under enriched cholesterol diet, which do not show such deficiencies.
      These findings indicate that cholesterol diet can protect against or counteract
      anesthesia/infusion-induced cognitive deficits. Ultimately, these results suggest
      that cholesterol homeostasis serves an important functional role in the brain and
      that altering this homeostasis can either exert positive or negative effects on
      cognitive properties. 

PMID- 23973450
TI  - Tagliatelle technique for arteriovenous fistula creation using a great saphenous
      vein semipanel graft.
AB  - Lower limb arteriovenous (AV) access creation can be attempted in patients where
      upper limb options are exhausted. Utilization of the great saphenous vein as a
      conduit for AV access has been limited due to its small diameter and resistance
      to dilatation. Lower limb AV fistulas today are mostly either prosthetic grafts
      with high rates of infection and thrombosis or transposition of the femoral vein
      that can lead to limb-threatening venous hypertension. In this report, we
      describe an optimized technique for reconstruction of the great saphenous vein to
      serve as a dialysis conduit. This semipanel graft reconstruction effectively
      doubles the diameter of the conduit without disruption of the deep venous
      circulation and also mitigates the requirement for a venovenous anastomosis. 

PMID- 23973451
TI  - Three-dimensional ultrasound-guided placement of ventricular catheters.
AB  - OBJECTIVE: Many studies demonstrate that the accuracy of freehand catheter
      placement for cerebrospinal fluid drainage is suboptimal. The aim of placement
      should be a single pass with a free-floating catheter tip in the intended
      position. The objective of this study was to achieve an accurate and user
      friendly system for three-dimensional (3D) ultrasound-navigated catheter
      placement through a regular burr hole. METHODS: A new phased-array ultrasound
      burr hole probe (4-10 MHz, 8 mm*9 mm footprint) was especially developed and
      optimized for navigated 3D ultrasound with the SonoWand Invite system. A catheter
      holder for optical tracking was also developed. Head immobilization was achieved
      with a vacuum cushion. With the described setup, 4 patients underwent surgery.
      RESULTS: Ultrasound image quality and visualization of the ventricles was good in
      all cases. Optimal placement of the catheter was achieved in a single pass in all
      patients. One of the trajectories was slightly more medial on postoperative
      computed tomography than anticipated from the neuronavigation system. None of the
      patients experienced any adverse event related to the procedure. CONCLUSIONS: 3D
      ultrasound with the described setup is a promising technique for accurate, fast,
      and user-friendly navigated placement of catheters for cerebrospinal fluid
      diversion.

PMID- 23973452
TI  - An anatomic review of thalamolimbic fiber tractography: ultra-high resolution
      direct visualization of thalamolimbic fibers anterior thalamic radiation,
      superolateral and inferomedial medial forebrain bundles, and newly identified
      septum pellucidum tract.
AB  - BACKGROUND: Images obtained through ultra-high-field 7.0-tesla magnetic resonance
      imaging with track-density imaging provide clear, high-resolution tractograms
      that have been hitherto unavailable, especially in deep brain areas such as the
      limbic and thalamic regions. This study is a largely pictorial description of the
      deep fiber tracts in the brain using track-density images obtained with 7.0-T
      diffusion-weighted imaging. METHODS: To identify the fiber tracts, we selected 3
      sets of tractograms and performed interaxis correlation between them. These
      tractograms offered an opportunity to extract new information in areas that have
      previously been difficult to examine using either in vivo or in vitro human brain
      tractography. RESULTS: With this new technique, we identified 4 fiber tracts that
      have not previously been directly visualized in vivo: septum pellucidum tract,
      anterior thalamic radiation, superolateral medial forebrain bundle, and
      inferomedial forebrain bundle. CONCLUSIONS: We present the high-resolution images
      as a tool for researchers and clinicians working with neurodegenerative and
      psychiatric diseases, such as Parkinson disease, Alzheimer disease, and
      depression, in which the accurate positioning of deep brain stimulation is
      essential for precise targeting of nuclei and fiber tracts.

PMID- 23973453
TI  - Crystal structure of the Pseudomonas aeruginosa cytoplasmic heme binding protein,
      Apo-PhuS.
AB  - Iron is an essential element to all living organisms and is an important
      determinant of bacterial virulence. Bacteria have evolved specialized systems to
      sequester and transport iron from the environment or host. Pseudomonas
      aeruginosa, an opportunistic pathogen, uses two outer membrane receptor mediated
      systems (Phu and Has) to utilize host heme as a source of iron. PhuS is a 39 kDa
      soluble cytoplasmic heme binding protein which interacts and transports heme from
      the inner membrane heme transporter to the cytoplasm where it is degraded by heme
      oxygenase thus releasing iron. PhuS is unique among other cytoplasmic heme
      transporter proteins owing to the presence of three histidines in the heme
      binding pocket which can potentially serve as heme ligands. Out of the three
      histidine residues on the heme binding helix, His 209 is conserved among heme
      trafficking proteins while His 210 and His 212 are unique to PhuS. Here we report
      the crystal structure of PhuS at 1.98A resolution which shows a unique heme
      binding pocket and oligomeric structure compared to other known cytoplasmic heme
      transporter and accounts for some of the unusual biochemical properties of PhuS.

PMID- 23973454
TI  - Quality evaluation of commercial Huang-Lian-Jie-Du-Tang based on simultaneous
      determination of fourteen major chemical constituents using high performance
      liquid chromatography.
AB  - Huang-Lian-Jie-Du-Tang (HLJDT), comprising Coptidis Rhizoma, Scutellariae Radix,
      Phellodendri Cortex and Gardeniae Fructus, is one of the commonly used Chinese
      medicine formulas for clearing heat and detoxifying. Quality control of the
      herbal complex like Chinese medicine formulas still remains a challenge. The
      successful approval of botanical drug Veregen by FDA indicated the importance of
      quantitative analysis in quality control of herbal medicines. In this study, an
      effective quantitative method based on conventional HPLC-DAD was developed for
      simultaneous determination of fourteen major ingredients (seven alkaloids, four
      flavonoids, three terpenes) in HLJDT. The established method was well validated
      in terms of linearity, sensitivity, precision, accuracy and stability and then
      successfully applied to quality evaluation of commercial HLJDT samples. The
      developed method can quantitatively determine up to 70% of the chemicals of
      commercial HLJDT sample and effectively revealed the significant variation in the
      quality of the commercial HLJDT samples collected from different locations. 

PMID- 23973455
TI  - [Delineation for oral cavity and oropharyngeal cancers].
AB  - The aim of this article is to present the determination and the delineation of
      target volumes for oral cavity and oropharyngeal carcinomas treated with
      intensity-modulated irradiation. The delineation on the computerized tomography
      scanner (CT scan) requires a precise method because of the complexity of the head
      and-neck anatomy. Different elements are necessary: clinical examination, diagram
      of the initial tumor, surgical and pathological reports and medical imaging (CT
      scan, magnetic resonance imaging and fluorodeoxyglucose positron emission
      tomography). The clinical target volumes, the planning target volumes, the organs
      at risk and the planning organs at risk volumes are discussed. The concept of
      selectivity of the potential subclinical disease near the primary tumour and the
      selection of neck nodal targets are specified according to the literature. 

PMID- 23973456
TI  - [Radiotherapy of brain metastases according to the GPA score (Graded Prognostic
      Assessment)].
AB  - The management of patients with brain metastases remains a difficult and
      controversial subject. For years, the standard treatment has been whole-brain
      radiation therapy alone, but its validity is now under question because of
      improvements in surgery and the development of radiosurgery or novel targeted
      therapies and also because whole-brain radiation therapy is responsible for long
      term neurocognitive toxicity. Therefore it is important to assess diagnosis
      specific prognostic factors and indexes when scheduling treatments. The GPA score
      (Graded Prognostic Assessment), established for various histologic tumor types,
      includes five prognostic factors: age, Karnofsky Performance Status, presence of
      extracranial metastases, number of brain metastases and also genetic subtype for
      breast cancer. We propose an adaptation of the management of brain metastases
      according to the GPA score. 

PMID- 23973457
TI  - [Guidelines for the delineation of the lymph nodes areas in gynecological
      malignancies].
AB  - Gynecological cancers are lymphophilic cancers, which require the systematic
      inclusion of nodal areas in the clinical target volume when irradiation is
      planned in the therapeutic strategy for these cancers. Radiotherapy with
      intensity modulation that achieves better saving of healthy tissue is more often
      used. However, the very steep dose gradients generated by this technique can lead
      to poorer coverage of target volumes if they are not defined very precisely by
      taking into account their anatomical location. This is particularly true for
      lymph node target volumes, so the purpose of this article is to present
      recommendations from a literature review focused on this issue, in terms of
      selection and delineation of lymph node in irradiation of cervix and endometrial
      cancers. 

PMID- 23973458
TI  - [Choice of optimal margins in prostate conformal radiotherapy].
AB  - The planning CT allows the delineation of the prostate (clinical target volume,
      CTV) but with an imprecision at the apex and the inability to visualize the
      intraprostatic cancer. MRI enables accurate visualization of the prostate
      outlines and in some extent the intraprostatic tumour (gross tumour volume
      [GTV]). The integration of MRI data within the CT remains still complex. Analysis
      of prostatectomy specimen has guided the definition of a CTV beyond the capsule,
      depending on pretreatment factors. In practice, the CTV can be defined as
      follows: prostate-only, for good prognosis tumours; prostate (+0 to 5mm margins,
      excluding the rectum) and seminal vesicles (possibly limited to 2 cm of their
      proximal region) for intermediate-risk tumours; prostate (+5mm margins) and
      seminal vesicles for high-risk tumours. The planning target volume (PTV) should
      be between 5mm and 10mm depending on the space directions, in the absence of
      image-guidance (IGRT). It could be reduced to 5mm in case of IGRT. In the
      adjuvant setting after prostatectomy, the definition of the CTV should follow the
      recommendations from cooperative groups. It takes into account both the analysis
      of pattern of local recurrence after prostatectomy, but also the specific
      histological analysis of the surgical specimen of the patient. The corresponding
      PTV margin is 6 to 8mm.

PMID- 23973459
TI  - [Positron emission tomography for volume delineation of pelvic nodal
      involvement].
AB  - Radiotherapy planification has recently known important developments, with the
      rise of new technologies, such as conformational radiation therapy, intensity
      modulated radiation therapy (IMRT) or stereotaxic radiation therapy. Delineation
      of target volumes has become primordial. Hybrid imaging by positron emission
      tomography associated to computed tomography scanner (PET-CT) gives an access to
      functional and morphological information. Radiotherapist and nuclear physicians
      working closely have the potential to allow a more optimal delineation, and a
      better preservation of organs at risk. During the past few years, this has been
      explored by many articles, and we propose a literature review organized by
      localization, about the use of PET-CT for pelvic nodes delineation. 

PMID- 23973448
TI  - Cellular, molecular, and genetic substrates underlying the impact of nicotine on
      learning.
AB  - Addiction is a chronic disorder marked by long-lasting maladaptive changes in
      behavior and in reward system function. However, the factors that contribute to
      the behavioral and biological changes that occur with addiction are complex and
      go beyond reward. Addiction involves changes in cognitive control and the
      development of disruptive drug-stimuli associations that can drive behavior. A
      reason for the strong influence drugs of abuse can exert on cognition may be the
      striking overlap between the neurobiological substrates of addiction and of
      learning and memory, especially areas involved in declarative memory. Declarative
      memories are critically involved in the formation of autobiographical memories,
      and the ability of drugs of abuse to alter these memories could be particularly
      detrimental. A key structure in this memory system is the hippocampus, which is
      critically involved in binding multimodal stimuli together to form complex long
      term memories. While all drugs of abuse can alter hippocampal function, this
      review focuses on nicotine. Addiction to tobacco products is insidious, with the
      majority of smokers wanting to quit; yet the majority of those that attempt to
      quit fail. Nicotine addiction is associated with the presence of drug-context and
      drug-cue associations that trigger drug seeking behavior and altered cognition
      during periods of abstinence, which contributes to relapse. This suggests that
      understanding the effects of nicotine on learning and memory will advance
      understanding and potentially facilitate treating nicotine addiction. The
      following sections examine: (1) how the effects of nicotine on hippocampus
      dependent learning change as nicotine administration transitions from acute to
      chronic and then to withdrawal from chronic treatment and the potential impact of
      these changes on addiction, (2) how nicotine usurps the cellular mechanisms of
      synaptic plasticity, (3) the physiological changes in the hippocampus that may
      contribute to nicotine withdrawal deficits in learning, and (4) the role of
      genetics and developmental stage (i.e., adolescence) in these effects. 

PMID- 23973460
TI  - [Hypofractionated radiotherapy in prostate cancer].
AB  - Radiotherapy plays a central role in the management of localized prostate cancer,
      but the total duration of treatment of nearly 2 months poses not only problems of
      fatigue related to repetitive transports, especially for older patients, but also
      increases the overall cost of treatment including linear accelerators occupancy
      and patient transportation. To address this problem, various teams have developed
      hypofractionated radiotherapy protocols seeking to maintain the same efficacy and
      toxicity while reducing the total duration of treatment. These hypofractionated
      protocols require recent techniques such as image-guided radiation therapy (IGRT)
      and intensity-modulated radiation therapy (IMRT). Single centre series have
      validated the feasibility of "light" hypofractionation schemes at doses per
      fraction less than 6 Gy Similarly, different teams have shown the possibility of
      stereotactic irradiation for delivering "severe" hypofractionation schemes at
      doses greater than 6 Gy per fraction. Whatever the dose per fraction, the current
      clinical data support the conclusion that hypofractionated radiotherapy does not
      increase mid-term toxicity and could even improve biochemical control. Studies
      with the objective of demonstrating non-inferiority are expected to definitively
      validate the role of hypofractionated irradiation in the treatment of prostate
      cancer.

PMID- 23973461
TI  - RNF38 encodes a nuclear ubiquitin protein ligase that modifies p53.
AB  - The RNF38 gene encodes a RING finger protein of unknown function. Here we
      demonstrate that RNF38 is a functional ubiquitin protein ligase (E3). We show
      that RNF38 isoform 1 is localized to the nucleus by a bipartite nuclear
      localization sequence (NLS). We confirm that RNF38 is a binding partner of p53
      and demonstrate that RNF38 can ubiquitinate p53 in vitro and in vivo. Finally, we
      show that overexpression of RNF38 in HEK293T cells results in relocalization of
      p53 to discrete foci associated with PML nuclear bodies. These results suggest
      RNF38 is an E3 ubiquitin ligase that may play a role in regulating p53. 

PMID- 23973462
TI  - Virulence and antibiotic resistance of Enterococcus faecalis clinical isolates
      recovered from three states of Mexico. Detection of linezolid resistance.
AB  - BACKGROUND AND AIMS: The virulence of Enterococcus faecalis is associated with
      three proteins involved in biofilm production: Ace, Agg, and Esp. Isolates also
      vary with respect to drug resistance. The present study investigated four
      characteristics of clinical isolates of E. faecalis recovered from three
      hospitals in Mexico, including biofilm production, the presence of biofilm
      related genes, antibiotic susceptibility, and clonal diversity. METHODS: We
      studied 109 clinical isolates. Biofilm formation was investigated using crystal
      violet and the safranin method with biofilm index correction. The presence of
      ace, agg, and esp genes was determined by PCR. Susceptibility to antibiotics was
      determined by the broth microdilution method and clonal relatedness was
      determined by pulsed-field gel electrophoresis (PFGE). RESULTS: Using the crystal
      violet method, 4.6% (5/109) of isolates were high biofilm producers, 48% (52/109)
      were moderate producers, 20% (39/109) were low producers, and 11% (12/109) were
      nonproducers. The agg gene was present in 44% (48/109), the ace gene in 39%
      (43/109), and the esp gene in 33% (36/109). The esp gene was associated with
      biofilm production (p <0.001), whereas the ace gene correlated with tetracycline
      resistance (p <0.01). The biofilm index was associated with the presence of both
      esp plus agg in glucose medium (p = 0.006). Clinical isolates showed high
      resistance to tetracycline and ciprofloxacin. Also, 2% of isolates were resistant
      to linezolid and there was no vancomycin resistance. PFGE revealed 109 different
      restriction patterns. CONCLUSIONS: The presence of the esp and agg gene was
      associated with biofilm production, whereas the presence of the ace gene
      correlated with tetracycline resistance. Overall, a moderate resistance to
      antibiotics was detected and there was no clonal relatedness among isolates.

PMID- 23973463
TI  - Dynamic localization and functional implications of C-peptide might for
      suppression of iNOS in high glucose-stimulated rat mesangial cells.
AB  - Although C-peptide has unique beneficial effects on diabetic nephropathy (DN),
      its functional localization and molecular mechanism have not been fully
      clarified. Whether C-peptide exhibits its protective role through the regulation
      of inducible nitric oxide synthase (iNOS), a key enzyme in oxidative stress, is
      not clear. In this study, it was revealed that C-peptide could enter the nucleus
      of high glucose-stimulated mesangial cells, especially in a time-dependent manner
      by high glucose pretreatment, while no C-peptide was detected in low glucose
      cultured mesangial cells. The dynamic functional localization of C-peptide might
      be the intrinsic cause of its unique beneficial effects for DN, which may provide
      a foundation for further clarification of its underlying mechanism. Our
      preliminarily data also shown C-peptide suppressed the iNOS expression. Taking
      together, these results revealed the dynamic functional localization of C-peptide
      by high glucose stimulation in rat mesangial cells, which might suppress
      expression of iNOS to exhibit its protective effects. 

PMID- 23973464
TI  - Phonological abstraction without phonemes in speech perception.
AB  - Recent evidence shows that listeners use abstract prelexical units in speech
      perception. Using the phenomenon of lexical retuning in speech processing, we ask
      whether those units are necessarily phonemic. Dutch listeners were exposed to a
      Dutch speaker producing ambiguous phones between the Dutch syllable-final
      allophones approximant [r] and dark [l]. These ambiguous phones replaced either
      final /r/ or final /l/ in words in a lexical-decision task. This differential
      exposure affected perception of ambiguous stimuli on the same allophone continuum
      in a subsequent phonetic-categorization test: Listeners exposed to ambiguous
      phones in /r/-final words were more likely to perceive test stimuli as /r/ than
      listeners with exposure in /l/-final words. This effect was not found for test
      stimuli on continua using other allophones of /r/ and /l/. These results confirm
      that listeners use phonological abstraction in speech perception. They also show
      that context-sensitive allophones can play a role in this process, and hence that
      context-insensitive phonemes are not necessary. We suggest there may be no one
      unit of perception. 

PMID- 23973466
TI  - Selfless giving.
AB  - In four studies, we show that people who anticipate more personal change over
      time give more to others. We measure and manipulate participants' beliefs in the
      persistence of the defining psychological features of a person (e.g., his or her
      beliefs, values, and life goals) and measure generosity, finding support for the
      hypothesis in three studies using incentive-compatible charitable donation
      decisions and one involving hypothetical choices about sharing with loved ones. 

PMID- 23973465
TI  - Infant directed speech and the development of speech perception: enhancing
      development or an unintended consequence?
AB  - Infant directed speech (IDS) is a speech register characterized by simpler
      sentences, a slower rate, and more variable prosody. Recent work has implicated
      it in more subtle aspects of language development. Kuhl et al. (1997)
      demonstrated that segmental cues for vowels are affected by IDS in a way that may
      enhance development: the average locations of the extreme "point" vowels (/a/,
      /i/ and /u/) are further apart in acoustic space. If infants learn speech
      categories, in part, from the statistical distributions of such cues, these
      changes may specifically enhance speech category learning. We revisited this by
      asking (1) if these findings extend to a new cue (Voice Onset Time, a cue for
      voicing); (2) whether they extend to the interior vowels which are much harder to
      learn and/or discriminate; and (3) whether these changes may be an unintended
      phonetic consequence of factors like speaking rate or prosodic changes associated
      with IDS. Eighteen caregivers were recorded reading a picture book including
      minimal pairs for voicing (e.g., beach/peach) and a variety of vowels to either
      an adult or their infant. Acoustic measurements suggested that VOT was different
      in IDS, but not in a way that necessarily supports better development, and that
      these changes are almost entirely due to slower rate of speech of IDS.
      Measurements of the vowel suggested that in addition to changes in the mean,
      there was also an increase in variance, and statistical modeling suggests that
      this may counteract the benefit of any expansion of the vowel space. As a whole
      this suggests that changes in segmental cues associated with IDS may be an
      unintended by-product of the slower rate of speech and different prosodic
      structure, and do not necessarily derive from a motivation to enhance
      development. 

PMID- 23973467
TI  - Modifications of the acidic soluble salivary proteome in human children from
      birth to the age of 48months investigated by a top-down HPLC-ESI-MS platform.
AB  - During the first year of life the infant oral environment undergoes dramatic
      changes. To investigate how the salivary proteome of human children evolves
      during infant development we have analyzed whole saliva of 88 children aged
      between 0 and 48months by a top-down platform based on RP-HPLC-ESI-MS. Children
      were divided according to their age into five groups (A, 0-6months, N=17; B, 7
      12months, N=14; C, 13-24months, N=32; D, 25-36months, N=16; E, 37-48months, N=9).
      The proteins and peptides analyzed were histatins (histatin-1, histatin-3 1/24),
      acidic proline-rich proteins, statherin, P-B peptide, and salivary cystatins.
      Protein and peptide quantification based on the area of the RP-HPLC-ESI-MS
      extracted ion current peak evidenced that: (i) concentrations of the major
      salivary proteins/peptides showed a minimum in the 0-6-month-old group and
      increased with age; (ii) the level of histatin-1 reached a maximum in the 7-12
      month-old group, a minimum in the 13-24-month-aged babies and it increased again
      in the 25-36-month-old group; (iii) S-type cystatins were almost undetectable in
      the 0-6-month-old group; (iv) P-B peptide concentration greatly increased with
      age; (v) histatin-3 1/24 and statherin concentrations did not show any age
      related variation. BIOLOGICAL SIGNIFICANCE: The top-down proteomic approach
      undertaken in this work reveals that the salivary proteome of human children from
      birth to 48months of age shows important quantitative modifications. The
      concentrations of the major salivary proteins, with the exception of statherin
      and histatin-3 1/24, showed a minimum in the 0-6-month-old group when the
      expression in salivary glands is probably not fully activated. Concentrations of
      the salivary proteins slowly increased with age, with different trends. Only
      histatin-1 showed the highest concentration in the 7-12-month-old group, followed
      by a decrease in the 13-24-month-aged children. This particular trend could be
      related to the phenomenon of eruption of primary dentition. This study gives a
      contribution to the knowledge on the physiological variability occurring in human
      saliva during the early childhood. It could represent a strong and reliable basis
      for further investigation of saliva to develop diagnostic and prognostic
      biomarkers.

PMID- 23973468
TI  - Gel-free proteomics reveal potential biomarkers of priming-induced salt tolerance
      in durum wheat.
AB  - Seed priming has been successfully demonstrated to be an efficient method to
      improve crop productivity under stressful conditions. As a first step toward
      better understanding of the mechanisms underlying the priming-induced salt stress
      tolerance in durum wheat, and to overcome the limitations of the gel-based
      approach, a comparative gel-free proteomic analysis was conducted with durum
      wheat seed samples of varying vigor as generated by hydro- and ascorbate-priming
      treatments. Results indicate that hydro-priming was accompanied by significant
      changes of 72 proteins, most of which are involved in proteolysis, protein
      synthesis, metabolism and disease/defense response. Ascorbate-priming was,
      however, accompanied by significant changes of 83 proteins, which are mainly
      involved in protein metabolism, antioxidant protection, repair processes and,
      interestingly, in methionine-related metabolism. The present study provides new
      information for understanding how 'priming-memory' invokes seed stress tolerance.
      BIOLOGICAL SIGNIFICANCE: The current work describes the first study in which gel
      free shotgun proteomics were used to investigate the metabolic seed protein
      fraction in durum wheat. A combined approach of protein fractionation, hydrogel
      nanoparticle enrichment technique, and gel-free shotgun proteomic analysis
      allowed us to identify over 380 proteins exhibiting greater molecular weight
      diversity (ranging from 7 to 258kDa). Accordingly, we propose that this approach
      could be useful to acquire a wider perspective and a better understanding of the
      seed proteome. In the present work, we employed this method to investigate the
      potential biomarkers of priming-induced salt tolerance in durum wheat. In this
      way, we identified several previously unrecognized proteins which were never been
      reported before, particularly for the ascorbate-priming treatment. These findings
      could provide new avenues for improving crop productivity, particularly under
      unfavorable environmental conditions.

PMID- 23973469
TI  - Proteomic profiling of the surface-exposed cell envelope proteins of Caulobacter
      crescentus.
AB  - Biotinylation of intact cells, avidin enrichment of derivatized peptides, and
      shotgun proteomics were employed to reveal the composition of the surface-exposed
      proteome of the aquatic bacterium, Caulobacter crescentus. Ninety-one unique
      proteins were identified with the majority originating from the outer membrane,
      periplasm, and inner membrane, subcellular regions that comprise the Gram
      negative bacterium cell envelope. Many of these proteins were described as
      'conserved hypothetical protein' or 'hypothetical protein'; and so, the actual
      expression of these gene products was confirmed. Others did not have any known
      function or lacked annotation. However, this investigation of the Caulobacter
      surfaceome did reveal the unanticipated presence of a number of enzymes involved
      in protein degradation. BIOLOGICAL SIGNIFICANCE: The results presented here can
      provide a starting point for hypothesis-driven research projects focused on this
      bacterium in particular and centered on understanding Gram-negative cell
      architecture and outer membrane biogenesis broadly. The detected protein
      degradation enzymes anchored on or located within the outer membrane suggest that
      Caulobacter has nutrient sources larger than small molecules and/or further
      processes surface proteins once secreted to this location. Additionally,
      confirmation of outer membrane residency of those proteins predicted to be
      periplasmic or whose location prediction was not definitive could potentially
      elucidate the identities of Gram-negative specific anchorless surface proteins.
      This article is part of a Special Issue entitled: Trends in Microbial Proteomics.

PMID- 23973470
TI  - Bioaugmentation of a polychlorobiphenyl contaminated soil with two aerobic
      bacterial strains.
AB  - The consortium of aerobic bacterial strains Rhodococcus ruber P25 and
      Microbacterium sp. B51 was bioaugmented in natural and industrial soils,
      contaminated by commercial mixture of polychlorinated biphenyls (PCBs) Sovol. The
      results showed that the bioaugmentation of bacterial strains led to PCBs
      degradation in soil. Sovol at the initial concentration of about 100 mg kg(-1)
      was removed by 72.2% in the bioaugmented system with natural soil within 90 days,
      while the system with industrial soil removed 96.4% of this compound within the
      same period. The biodegradation kinetics of PCBs in the bioaugmented soil systems
      was not dependent on the presence of indigenous microflora. It was found that the
      growth dynamics of the strains R. ruber P25 and Microbacterium sp. B51 correlated
      with the specific degradation of Sovol. The strains R. ruber P25 and
      Microbacterium sp. B51 displayed high degradative activity to all congeners
      (ortho-, meta- and para-substituent) contained in Sovol. Removal percentage for
      each congeners amounted to 59-100% in the bioaugmented systems. This study
      suggests that augmentation of PCB-contaminated soils with strain R. ruber P25 and
      Microbacterium sp. B51 is promising in PCB bioremediation.

PMID- 23973471
TI  - Factorial kriging and stepwise regression approach to identify environmental
      factors influencing spatial multi-scale variability of heavy metals in soils.
AB  - The knowledge about spatial variations of heavy metals in soils and their
      relationships with environmental factors is important for human impact assessment
      and soil management. Surface soils from Rizhao city, Eastern China with rapid
      urbanization and industrialization were analyzed for six key heavy metals and
      characterized by parent material and land use using GIS-based data. Factorial
      kriging analysis and stepwise multiple regression were applied to examine the
      scale-dependent relationships among heavy metals and to identify environmental
      factors affecting spatial variability at each spatial scale. Linear model of
      coregionalization fitting showed that spatial multi-scale variation of heavy
      metals in soils consisted of nugget effect, an exponential structure with the
      range of 12 km (short-range scale), as well as a spherical structure with the
      range of 36 km (long-range scale). The short-range variation of Cd, Pb and Zn
      were controlled by land use, with higher values in urban areas as well as
      cultivated land in mountain area, and were related to human influence; while
      parent material dominated the long structure variations of these elements.
      Spatial variations of Cr and Ni were associated with natural geochemical sources
      at short- and long-range scales. At both two scales, Hg dominated by land use,
      corresponded well to spatial distributions of urban areas, and was attributed to
      anthropic emissions and atmosphere deposition.

PMID- 23973472
TI  - Synthesis of cuprous chloride and simultaneous recovery of Ag and Pd from waste
      printed circuit boards.
AB  - A benign and effective process for cuprous chloride synthesis and simultaneously
      recovery of Ag and Pd from waste printed circuit boards (PCBs) was developed in
      the present study. The main merit of the process is that neither corrosive acid
      nor strong oxidant was used. The PCBs were firstly pretreated by thermal shock
      process to obtain metallic particles (MPs), then cuprous chloride was synthesized
      by reacting MPs with cupric sulfate in the presence of sodium chloride. The
      optimum [Formula: see text] (mL/g) ratio, [Cu]/[Cu(2+)] mole ratio, treatment
      time and operation temperature were 6, 0.95, 30 min and 60 degrees C,
      respectively. Approximately 98.5% of Cu could be recovered from the PCBs through
      two synthesis circles. During the synthesis process, Ag and Pd could be
      simultaneously recovered by forming a stable chloride complex since Cu(2+) played
      the role of oxidant in the system. The recovery percentages of Ag and Pd were
      93.9% and 95.3%, respectively. Accordingly, it is believed that the process
      developed in the current study is benign and practical for copper and precious
      metal (Ag, Pd) recovery from waste PCBs.

PMID- 23973473
TI  - The influence of calcium and pH on the uptake and toxicity of copper in Folsomia
      candida exposed to simplified soil solutions.
AB  - The aim of the present study was to investigate the influence of Ca and pH on the
      uptake and effects of Cu in Folsomia candida (Collembola). Assuming that soil
      pore water is the main route of exposure, F. candida were exposed for seven days
      to Cu in simplified soil solutions at different Ca concentrations and different
      pH levels. A hormetic-type effect was seen for the effect of Cu on F. candida
      survival. Toxicity of Cu was slightly decreased and Cu uptake increased at the
      highest Ca concentrations. Cu toxicity and uptake were not significantly affected
      by pH. Conditional binding constants for Cu(2+), Ca(2+) and H(+), calculated with
      a Langmuir isotherm, were used to relate Cu toxicity to the fraction of occupied
      binding sites (BL). The estimated 50% effect level (fCu-BL50) was 0.14 when all
      data were combined. To verify the Langmuir parameters, binding constants
      calculated based on internal Cu concentrations were used to estimate predicted
      effects and compared with the measured values. A good correlation between
      predicted and measured survival indicated that the principles of a biotic ligand
      model may be applicable to explain Cu toxicity to F. candida in simplified soil
      solutions.

PMID- 23973474
TI  - Removal of silver nanoparticles by coagulation processes.
AB  - Commercial use of silver nanoparticles (AgNPs) will lead to a potential route for
      human exposure via potable water. Coagulation followed by sedimentation, as a
      conventional technique in the drinking water treatment facilities, may become an
      important barrier to prevent human from AgNP exposures. This study investigated
      the removal of AgNP suspensions by four regular coagulants. In the aluminum
      sulfate and ferric chloride coagulation systems, the water parameters slightly
      affected the AgNP removal. However, in the poly aluminum chloride and polyferric
      sulfate coagulation systems, the optimal removal efficiencies were achieved at pH
      7.5, while higher or lower of pH could reduce the AgNP removal. Besides, the
      increasing natural organic matter (NOM) would reduce the AgNP removal, while
      Ca(2+) and suspended solids concentrations would also affect the AgNP removal. In
      addition, results from the transmission electron microscopy and X-ray diffraction
      showed AgNPs or silver-containing nanoparticles were adsorbed onto the flocs.
      Finally, natural water samples were used to validate AgNP removal by coagulation.
      This study suggests that in the case of release of AgNPs into the source water,
      the traditional water treatment process, coagulation/sedimentation, can remove
      AgNPs and minimize the silver ion concentration under the well-optimized
      conditions.

PMID- 23973475
TI  - Concentrations, profiles, and emission factors of unintentionally produced
      persistent organic pollutants in fly ash from coking processes.
AB  - The coking process has been found to be an important source of unintentionally
      produced persistent organic pollutants (UP-POPs). However, the concentrations,
      profiles, and emission factors of UP-POPs in fly ash from coke plants have not
      been studied. In this study, six UP-POPs (polychlorinated dibenzo-p-dioxins
      (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs),
      polychlorinated naphthalenes (PCNs), hexachlorobenzene (HxCBz), and
      pentachlorobenzene (PeCBz)) were identified and quantified in fly ash from eight
      coke plants. The average concentrations of the PCDDs, PCDFs, and "dioxin-like"
      PCBs were 1.5, 2.26, and 0.26 pg TEQ g(-1), respectively, and the average
      concentrations of the PCNs, HxCBz, and PeCBz were 256, 290, and 146 pg g(-1),
      respectively. The proportion each homolog contributed to the total concentration
      of the PCDFs, PCBs, and PCNs decreased with increasing chlorination level. The
      PCDFs contributed the biggest proportion of the total UP-POPs toxic equivalents
      (TEQs), and the average emission factors in fly ash were 10.5, 17.3, and 1.82 ng
      TEQt(-1) for the PCDDs, PCDFs, and "dioxin-like" PCBs, respectively, and 1,792,
      2,028, and 1,025 ngt(-1) for the PCNs, HxCBz, and PeCBz, respectively. These data
      are essential for establishing an integrated UP-POP release inventory.

PMID- 23973476
TI  - Flow analysis of heavy metals in a pilot-scale incinerator for residues from
      waste electrical and electronic equipment dismantling.
AB  - The large amount of residues generated from dismantling waste electrical and
      electronic equipment (WEEE) results in a considerable environmental burden. We
      used material flow analysis to investigate heavy metal behavior in an
      incineration plant in China used exclusively to incinerate residues from WEEE
      dismantling. The heavy metals tested were enriched in the bottom and fly ashes
      after incineration. However, the contents of heavy metals in the bottom ash, fly
      ash and exhaust gas do not have a significant correlation with that of the input
      waste. The evaporation and recondensation behavior of heavy metals caused their
      contents to differ with air pollution control equipment because of the
      temperature difference during gas venting. Among the heavy metals tested, Cd had
      the strongest tendency to transfer during incineration (TCd=69.5%) because it had
      the lowest melting point, followed by Cu, Ni, Pb and Zn. The exchangeable and
      residual fractions of heavy metals increased substantially in the incineration
      products compared with that of the input residues. Although the mass of residues
      from WEEE dismantling can be reduced by 70% by incineration, the safe disposal of
      the metal-enriched bottom and fly ashes is still required.

PMID- 23973477
TI  - Predicting the loss of phylogenetic diversity under non-stationary
      diversification models.
AB  - For many species, the current high rates of extinction are likely to result in a
      significant loss of biodiversity. The evolutionary heritage of biodiversity is
      frequently quantified by a measure called phylogenetic diversity (PD). We predict
      the loss of PD under a wide class of phylogenetic tree models, where speciation
      rates and extinction rates may be time-dependent, and assuming independent random
      species extinctions at the present. We study the loss of PD when K contemporary
      species are selected uniformly at random from the N extant species as the
      surviving species, while the remaining N-K become extinct (N and K being random
      variables). We consider two models of species sampling, the so-called field of
      bullets model, where each species independently survives the extinction event at
      the present with probability p, and a model for which the number of surviving
      species is fixed. We provide explicit formulae for the expected remaining PD in
      both models, conditional on N=n, conditional on K=k, or conditional on both
      events. When N=n is fixed, we show the convergence to an explicit deterministic
      limit of the ratio of new to initial PD, as n->infinity, both under the field of
      bullets model, and when K=kn is fixed and depends on n in such a way that kn/n
      converges to p. We also prove the convergence of this ratio as T->infinity in the
      supercritical, time-homogeneous case, where N simultaneously goes to infinity,
      thereby strengthening previous results of Mooers et al. (2012). 

PMID- 23973478
TI  - Consistency of Bayesian inference of resolved phylogenetic trees.
AB  - Bayesian inference is now a leading technique for reconstructing phylogenetic
      trees from aligned sequence data. In this short note, we formally show that the
      maximum posterior tree topology provides a statistically consistent estimate of a
      fully resolved evolutionary tree under a wide variety of conditions. This
      includes the inference of gene trees from aligned sequence data across the entire
      parameter range of branch lengths, and under general conditions on priors in
      models where the usual 'identifiability' conditions hold. We extend this to the
      inference of species trees from sequence data, where the gene trees constitute
      'nuisance parameters', as in the program (*)BEAST. This note also addresses
      earlier concerns raised in the literature questioning the extent to which
      statistical consistency for Bayesian methods might hold in general.

PMID- 23973479
TI  - Adsorption and flocculation of bentonite by chitosan with varying degree of
      deacetylation and molecular weight.
AB  - Chitosans with different degrees of deacetylation (DD) and molecular weights (Mw)
      were tested for the flocculation of bentonite suspensions prepared with
      demineralized water (DW) and tap water (TW), respectively. Flocculation kinetics
      model of particles collisions combining zeta potential and turbidity measurements
      was employed to investigate the effects of the DD and Mw of the chitosans on the
      flocculation properties. The results indicated that the chitosan (Mw 232 kDa)
      dosages required for maximum flocculation are 20 mg/L in DW and 5 mg/L in TW,
      respectively, regardless of DD from 54.6% to 95.2% and pH of bentonite
      suspension. Chitooligomers (Mw 1.5 kDa, DD 95.2%) failed to reach the required
      residual turbidity (i.e., 10 NTU) in DW under all investigated conditions,
      whereas good results were obtained using 5-20 mg/L in TW. The polymer-induced
      flocculation processed obeyed Von Smoluchowski's bimolecular rate equation. The
      flocculation performance in TW was very different from that in DW due to the
      presence of salts in TW. The results were consistent with the destabilization of
      bentonite by the combined mechanisms of charge neutralization and bridging.

PMID- 23973480
TI  - Synthesis, characterization, in vitro and in vivo evaluation of PEGylated
      oridonin conjugates.
AB  - Oridonin (ORI), a diterpenoid compound with promising antitumor activity, was
      proved to possess potent antileukemia efficacies in vitro and in vivo recently.
      However, the development and application of ORI was limited by its poor
      solubility and rapid plasma clearance. The purpose of this study was to solve
      these problems. PEGylated oridonin linked with succinic acid (SA) as spacer
      moiety (PEG-SA-ORI conjugate) was synthesized. mPEG amines with four
      specifications of molecular weight (MW) were utilized. All polymeric conjugates
      showed satisfactory aqueous solubility and in vitro studies implied that the drug
      solubility and release features of conjugates were relevant to PEGs. The drug
      solubility increased more when the MW of PEG was lower, while more significant
      sustained-release effect was shown with higher PEG MW. Moreover, the release
      behaviors of conjugates showed a pH-sensitive property. In vivo pharmacokinetic
      studies demonstrated that the elimination half-life was prolonged in comparison
      with ORI solution. PEGylation could be a promising method to obtain better
      efficacy in the field of drug delivery system. 

PMID- 23973481
TI  - Investigating the Ustilago maydis/Zea mays pathosystem: transcriptional responses
      and novel functional aspects of a fungal calcineurin regulatory B subunit.
AB  - The sustainable control of basidiomycete biotrophic plant pathogenesis requires
      an understanding of host responses to infection, as well as the identification
      and functional analysis of fungal genes involved in disease development. The
      creation and analysis of a suppressive subtractive hybridization (SSH) cDNA
      library from Ustilago maydis-infected Zea mays seedlings enabled the
      identification of fungal and plant genes expressed during disease development,
      and uncovered new insights into the interactions of this model system. Candidate
      U. maydis pathogenesis genes were identified by using the current SSH cDNA
      library analysis, and by knowledge generated from previous cDNA microarray and
      comparative genomic analyses. These identifications were supported by the
      independent determination of transcript level changes in different cell-types and
      during pathogenic development. The basidiomycete specific um01632, the highly in
      planta expressed um03046 (zig1), and the calcineurin regulatory B subunit
      (um10226, cnb1), were chosen for deletion experiments. um01632 and zig1 mutants
      showed no difference in morphology and did not have a statistically significant
      impact on pathogenesis. cnb1 mutants had a distinct cell division phenotype and
      reduced virulence in seedling assays. Infections with reciprocal wild
      type*Deltacnb1 haploid strain crosses revealed that the wild-type allele was
      unable to fully compensate for the lack of a second cnb1 allele. This
      haploinsufficiency was undetected in other fungal cnb1 mutational analyses. The
      reported data improves U. maydis genome annotation and expands on the current
      understanding of pathogenesis genes in this model basidiomycete. 

PMID- 23973482
TI  - Oxidative stress plays a role in high glucose-induced activation of pancreatic
      stellate cells.
AB  - The activation of pancreatic stellate cells (PSCs) is thought to be a potential
      mechanism underlying islet fibrosis, which may contribute to progressive beta
      cell failure in type 2 diabetes. Recently, we demonstrated that antioxidants
      reduced islet fibrosis in an animal model of type 2 diabetes. However, there is
      no in vitro study demonstrating that high glucose itself can induce oxidative
      stress in PSCs. Thus, PSCs were isolated and cultured from Sprague Dawley rats,
      and treated with high glucose for 72 h. High glucose increased the production of
      reactive oxygen species. When treated with high glucose, freshly isolated PSCs
      exhibited myofibroblastic transformation. During early culture (passage 1), PSCs
      treated with high glucose contained an increased number of alpha-smooth muscle
      actin-positive cells. During late culture (passages 2-5), PSCs treated with high
      glucose exhibited increases in cell proliferation, the expression of fibronectin
      and connective tissue growth factor, release of interleukin-6, transforming
      growth factor-beta and collagen, and cell migration. Finally, the treatment of
      PSCs with high glucose and antioxidants attenuated these changes. In conclusion,
      we demonstrated that high glucose increased oxidative stress in primary rat PSCs,
      thereby facilitating the activation of these cells, while antioxidant treatment
      attenuated high glucose-induced PSC activation.

PMID- 23973483
TI  - Picropodophyllin inhibits tumor growth of human nasopharyngeal carcinoma in a
      mouse model.
AB  - Insulin-like growth factor-1 receptor (IGF-1R) is a cell membrane receptor with
      tyrosine kinase activity and plays important roles in cell transformation, tumor
      growth, tumor invasion, and metastasis. Picropodophyllin (PPP) is a selective IGF
      1R inhibitor and shows promising antitumor effects for several human cancers.
      However, its antitumor effects in nasopharyngeal carcinoma (NPC) remain unclear.
      The purpose of this study is to investigate the antitumor activity of PPP in NPC
      using in vitro cell culture and in vivo animal model. We found that PPP dose
      dependently decreased the IGF-induced phosphorylation and activity of IGF-1R and
      consequently reduced the phosphorylation of Akt, one downstream target of IGF-1R.
      In addition, PPP inhibited NPC cell proliferation in vitro. The half maximal
      inhibitory concentration (IC50) of PPP for NPC cell line CNE-2 was <=1 MUM at 24h
      after treatment and <=0.5 MUM at 48 h after treatment, respectively. Moreover,
      administration of PPP by intraperitoneal injection significantly suppressed the
      tumor growth of xenografted NPC in nude mice. Taken together, these results
      suggest targeting IGF-1R by PPP may represent a new strategy for treatment of
      NPCs with positive IGF-1R expression.

PMID- 23973484
TI  - 6-Phosphogluconate dehydrogenase regulates tumor cell migration in vitro by
      regulating receptor tyrosine kinase c-Met.
AB  - 6-Phosphogluconate dehydrogenase (6PGD) is the third enzyme in the oxidative
      pentose phosphate pathway (PPP). Recently, we reported that knockdown of 6PGD
      inhibited lung tumor growth in vitro and in a xenograft model in mice. In this
      study, we continued to examine the functional role of 6PGD in cancer. We show
      that 6PGD expression positively correlates with advancing stage of lung
      carcinoma. In search of functional signals related to 6PGD, we discovered that
      knockdown of 6PGD significantly inhibited phosphorylation of c-Met at tyrosine
      residues known to be critical for activity. This downregulation of c-Met
      phosphorylation correlated with inhibition of cell migration in vitro.
      Overexpression of a constitutively active c-Met specifically rescued the
      migration but not proliferation phenotype of 6PGD knockdown. Therefore, 6PGD
      appears to be required for efficient c-Met signaling and migration of tumor cells
      in vitro. 

PMID- 23973485
TI  - Expression of budding yeast FKBP12 confers rapamycin susceptibility to the
      unicellular red alga Cyanidioschyzon merolae.
AB  - The target of rapamycin (TOR) is serine/threonine protein kinase that is highly
      conserved among eukaryotes and can be inactivated by the antibiotic rapamycin
      through the formation of a ternary complex composed of rapamycin and two
      proteins, TOR and FKBP12. Differing from fungi and animals, plant FKBP12 proteins
      are unable to form the ternary complex, and thus plant TORs are insensitive to
      rapamycin. This has led to a poor understanding of TOR functions in plants. As a
      first step toward the understanding of TOR function in a rapamycin-insensitive
      unicellular red alga, Cyanidioschyzon merolae, we constructed a rapamycin
      susceptible strain in which the Saccharomyces cerevisiae FKBP12 protein
      (ScFKBP12) was expressed. Treatment with rapamycin resulted in growth inhibition
      and decreased polysome formation in this strain. Binding of ScFKBP12 with C.
      merolae TOR in the presence of rapamycin was demonstrated in vivo and in vitro by
      pull-down experiments. Moreover, in vitro kinase assay showed that inhibition of
      C. merolae TOR kinase activity was dependent on ScFKBP12 and rapamycin. 

PMID- 23973486
TI  - Correlation of N-myc downstream-regulated gene 1 subcellular localization and
      lymph node metastases of colorectal neoplasms.
AB  - In colorectal neoplasms, N-myc downstream-regulated gene 1 (NDRG1) is a primarily
      cytoplasmic protein, but it is also expressed on the cell membrane and in the
      nucleus. NDRG1 is involved in various stages of tumor development in colorectal
      cancer, and it is possible that the different subcellular localizations may
      determine the function of NDRG1 protein. Here, we attempt to clarify the
      characteristics of NDRG1 protein subcellular localization during the progression
      of colorectal cancer. We examined NDRG1 expression in 49 colorectal cancer
      patients in cancerous, non-cancerous, and corresponding lymph node tissues.
      Cytoplasmic and membrane NDRG1 expression was higher in the lymph nodes with
      metastases than in those without metastases (P<0.01). Nuclear NDRG1 expression in
      colorectal neoplasms was significantly higher than in the normal colorectal
      mucosa, and yet the normal colorectal mucosa showed no nuclear expression.
      Furthermore, our results showed higher cytoplasmic NDRG1 expression was better
      for differentiation, and higher membrane NDRG1 expression resulted in a greater
      possibility of lymph node metastasis. These data indicate that a certain
      relationship between the cytoplasmic and membrane expression of NDRG1 in lymph
      nodes exists with lymph node metastasis. NDRG1 expression may translocate from
      the membrane of the colorectal cancer cells to the nucleus, where it is involved
      in lymph node metastasis. Combination analysis of NDRG1 subcellular expression
      and clinical variables will help predict the incidence of lymph node metastasis. 

PMID- 23973487
TI  - Two beta-strands of RAGE participate in the recognition and transport of amyloid
      beta peptide across the blood brain barrier.
AB  - Amyloid-beta (Abeta) peptide is central to the development of brain pathology in
      Alzheimer disease (AD) patients. Association with receptors for advanced
      glycation end-products (RAGE) enables the transport of Abeta peptide from
      circulating blood to human brain, and also causes the activation of the NF-kappaB
      signaling pathway. Here we show that two beta-strands of RAGE participate in the
      interaction with Abeta peptide. Serial deletion analysis of the RAGE V domain
      indicates that the third and eighth beta-strands are required for interaction
      with Abeta peptide. Site-directed mutagenesis of amino acids located in the third
      and eighth beta-strands abolish the interaction of RAGE with Abeta peptide. Wild
      type RAGE activates the NF-kappaB signaling pathway in response to Abeta peptide
      treatment, while a RAGE mutant defective in Abeta binding does not. Furthermore,
      use of peptide for the third beta-strand or a RAGE monoclonal antibody that
      targets the RAGE-Abeta interaction interface inhibited transport of the Abeta
      peptide across the blood brain barrier in a mice model. These results provide
      information crucial to the development of RAGE-derived therapeutic reagents for
      Alzheimer disease. 

PMID- 23973488
TI  - Apelin-13-induced proliferation and migration induced of rat vascular smooth
      muscle cells is mediated by the upregulation of Egr-1.
AB  - Apelin-13 plays an important role in the migration and proliferation of vascular
      smooth muscle cells (VSMCs); however, the underlying mechanisms are still
      unclear. Egr-1 is a nuclear transcription factor, which is considered to be the
      critical initiating factor of the processes of VSMC proliferation and migration.
      Egr-1 is known to regulate the expression of osteopontin (OPN), which is a marker
      of the phenotypic modulation that is a necessary condition of VSMC proliferation
      and migration. We hypothesized that the role of Apelin-13 is mediated via
      upregulation of Egr-1. To test this hypothesis, we analyzed the effects of Apelin
      13 treatment on Egr-1 mRNA and protein expression in A10 rat aortic VSMCs by RT
      PCR and Western blotting, respectively. Results showed that, Apelin-13
      upregulated the expression of Egr-1. Furthermore, treatment with the
      extracellular-regulated protein kinase (ERK) inhibitor, PD98059, inhibited the
      upregulation of Egr-1 by Apelin-13. In addition, this upregulation was inhibited
      by treatment of VSMCs with the Egr-1 specific deoxyribozyme ED5 (DNAenzyme/10-23
      DRz). Furthermore, ED5 treatment was found to significantly inhibit Apelin-13
      induced migration and proliferation of VSMCs using transwell and MTT assays,
      respectively. The evaluation of OPN mRNA and protein expression levels by RT-PCR
      and Western blot analyses revealed that ED5 treatment also inhibited Apelin-13
      induced OPN upregulation. The results of this study indicated that Apelin-13
      upregulates Egr-1 via ERK. Furthermore, Apelin-13 induced the proliferation and
      migration of VSMCs as well as the upregulation of OPN via the upregulation of Egr
      1. These results will provide an important theoretical and experimental basis for
      the control of inappropriate remodeling of vessel walls, and will hopefully lead
      to the prevention and treatment of vascular remodeling diseases. 

PMID- 23973489
TI  - Antioxidant activity and antibacterial activity of peach gum derived
      oligosaccharides.
AB  - In this study, peach gum derived oligosaccharides (PGDO) were prepared from peach
      gum polysaccharides by hydrolysis using hydrogen peroxide (H2O2) under following
      conditions: time, 8h; temperature, 55  degrees C; H2O2 concentration, 4% (v/v);
      and NaOH concentration, 2.0 M. The antioxidant activity and antibacterial
      activity of PGDO were estimated. There were no significant chemical changes in
      the backbones of the peach gum polysaccharides treated with H2O2. The PGDO showed
      high hydroxyl radical scavenging activity (86.12%) and 2, 2-diphenyl-beta
      picrylhydrazyl radical scavenging activity (91.70%) at the concentration of 100
      MUg/mL as well as high reducing capacity at the concentration of 50 MUg/mL. In
      addition the PGDO had high antibacterial activity against Bacillus subtilis,
      Staphylococcus aureus, and Escherichia coli at the concentration of 100 MUg/mL.

PMID- 23973490
TI  - Hydrolysis of isoflavone glycoside by immobilization of beta-glucosidase on a
      chitosan-carbon in two-phase system.
AB  - We explored a method to examine the hydrolysis of isoflavone glycoside by
      immobilizing beta-glucosidase on chitosan-carbon beads in an aqueous-organic two
      phase system. The chitosan-carbon beads were cross-linked with glutaraldehyde to
      immobilize beta-glucosidase from Exiguobacterium sp. DAU5. The optimal pH and
      temperature were 9.0 and 55  degrees C, respectively. Under the optimized
      conditions, crude and purified enzymes immobilized onto chitosan-carbon beads
      gave yields of 16.7% and 60%, respectively. The specific activities of
      immobilized crude and purified enzymes were 4.3 U/g and 6 U/g, respectively. The
      immobilized enzyme retained more than 80% of its maximum activity at pH 7.0-11.0,
      while temperature was more influential (80% activity after 40  degrees C for 1.5
      h, but only 40% activity after 55  degrees C for 0.5 h, respectively. The
      immobilized enzyme was able to hydrolyze isoflavone glycoside in an aqueous
      organic two-phase system, and the hydrolyzed products were enriched in the
      organic phase, making it easy to recover the products, i.e., genistein and
      daidein from the reaction system. These results suggest that immobilized beta
      glucosidase may be applicable for the industrial-scale hydrolysis of isoflavone
      glycoside.

PMID- 23973491
TI  - Carboxymethyl functionalization of amylopectin and its evaluation as a nanometric
      drug carrier.
AB  - Carboxymethylation of amylopectin was accomplished by reacting it with
      monochloroacetic acid. The results of characterization study confirmed the
      carboxymethyl functionalization with degree of substitution of 1.25.
      Carboxymethyl amylopectin was found to be slightly more crystalline, appearing
      morphologically as polyhedral flakes with striated surface. Further,
      carboxymethylation of amylopectin modified its compression characteristic from
      fragmentary to plastic. Interaction of carboxymethyl amylopectin (0.001-0.005%,
      w/v) with chitosan (0.05-0.075% w/v) using ibuprofen (0.05%, w/v) as a model drug
      provided polyelectrolyte nanoparticles of size 182.7-353.3 nm and 75-92% drug
      entrapment. The polyelectrolyte nanoparticles showed a sustained release of drug
      following zero-order kinetics with mechanism of release being combination of
      matrix erosion and diffusion through the matrix.

PMID- 23973492
TI  - Chitin extraction and characterization from Daphnia magna resting eggs.
AB  - New application areas for chitin and its derivatives have been extensively
      investigated and there is a solid, growing demand for new chitin sources. In this
      present study, chitin content of Daphnia magna resting egg (18-21%) was
      determined for the first time. FTIR, elemental analysis, TGA, XRD and SEM studies
      revealed the structural and thermal properties of extracted alpha-chitin. This
      study suggests that D. magna resting eggs can be exploited as an attractive
      alternative chitin source.

PMID- 23973493
TI  - Rheological properties and antitumor activity of schizophyllan produced with
      solid-state fermentation.
AB  - Schizophyllan (SPG) was produced by the fungus Schizophyllum commune under solid
      state fermentation conditions in this study. SPG was physically characterized and
      its rheological properties and antitumor effects on S180 tumors in vivo were
      evaluated. SPG is a neutral polysaccharide with three main fractions, and the
      major fraction comprises 55.5%, with an average molecular weight 4.65 * 10(7) Da.
      Steady shear rheological measurements showed the typical pseudoplastic flow
      behavior of SPG at the experimental concentrations. The power law model was used
      to fit the shear curves of SPG and both its viscosity and consistency indices
      changed regularly as the concentration increased. SPG solution showed different
      viscoelastic behaviors at different concentrations: typical viscoelastic behavior
      was observed at lower concentrations, whereas solid-like behavior was observed at
      higher concentrations. Experimental doses of SPG exerted extreme antitumor
      effects in vivo, and the maximum inhibition rate was almost 70%.

PMID- 23973494
TI  - Toxicological study of the primaquine phosphate loaded chitosan nanoparticles in
      mice.
AB  - Primaquine (PQ) shows activity against the late hepatic stages and latent tissue
      forms of Plasmodium vivax and Plasmodium ovale. However, liver targeted PQ
      delivery may be useful to minimize the dose-limiting blood toxicities and side
      effects of PQ. The prime objective of this study was the preparation of PQ loaded
      chitosan nanoparticles (PQ-CS-NPs) in order to enhance drug tolerance and to
      reduce dose frequency. The morphological analysis of the chitosan NPs displayed
      particle size in the range 287-686 nm, polydispersity index in the range 0.338
      0.430 and zeta potential between 9.21 and 22.80 mV which indicated good
      stability. PQ-CS-NPs exhibited EE and LC as 64.28 +/- 1.85% and 33.18 +/- 0.975%,
      respectively. The in vitro drug release (Batch C7) was 97.80 +/- 0.65% after 24
      h. After intravenous injection of PQ-CS-NPs in mice, the lethal dose of the PQ
      significantly reduced when compared to that of free PQ solution.

PMID- 23973495
TI  - Graft polymerization of guar gum with acryl amide irradiated by microwaves for
      colonic drug delivery.
AB  - This article is aimed to discuss the modification of guar gum through microwave
      irradiation by varying the time of irradiation. The characterization of the
      modified products was carried out using FTIR spectroscopic analysis. The FT-IR
      spectrum of the pure guar gum (GG) sample showed a broad peak at 3298 cm(-1)
      while the modified GG sample displayed a peak at 1541 cm(-1) which was absent in
      the crude sample. The X-ray diffraction (XRD) analysis confirmed the increase in
      crystallinity due to grafting of the sample with polyacrylamide (GG-g-PAM).
      Scanning electron microscope (SEM) images revealed that granular form of guar gum
      was changed into fibrillar structure after grafting. Thermo-gravimetric analysis
      of the modified samples was also carried out and discussed. The role of guar gum
      as a matrix for controlled release of drug triamcinolone was evaluated. The GG
      acrylamide grafted samples presented a correlation between drug release and time
      of microwave exposure. The results revealed that such modified product has
      potential applications in colonic drug delivery system.

PMID- 23973496
TI  - Chitosan-montmorillonite biocomposite as an adsorbent for copper (II) cations
      from aqueous solutions.
AB  - Chitosan-montmorillonite (KSF-CTS) beads were prepared by crosslinking with
      pentasodium tripolyphosphate (TPP). Montmorillonite (KSF-Na), CTS and KSF-CTS
      biocomposite were used to remove Cu(II) from aqueous solutions. These materials
      were characterized before and after copper adsorption by XRD, FTIR and
      thermogravimetry (TG). The data indicated that the adsorption process proceeds
      kinetically according to a pseudo-second-order model. The adsorption processes
      were adjusted to the Langmuir model for KSF-Na and CTS and to the Temkin model
      for KSF-CTS. The maximum adsorption capacity followed the order CTS>KSF-CTS>KSF
      Na. Percentages desorption of copper ions from the KSF-CTS composite after three
      desorption cycles were 86%, 85% and 84%, respectively, using EDTA as regeneration
      agents.

PMID- 23973497
TI  - Anti-tumor activity of the regenerated triple-helical polysaccharide from
      Dictyophora indusiata.
AB  - A triple helical polysaccharide (PD3) was isolated from Dictyophora indusiata.
      After denaturation in dilute NaOH solution (0.3 M) and renaturation by sequential
      dialysis, regenerated polysaccharide (RPD3) was obtained. The physico-chemical
      properties of RPD3 including intrinsic viscosity [eta], molecular weight (Mw) and
      optical rotation were similar to those of PD3, which suggested that RPD3 also had
      a triple helical structure after denaturation-renaturation. However, different
      intrinsic viscosity dependence on the concentration of NaOH solution was noted in
      PD3 and RPD3, which indicated that RPD3 had lower chain tightness compared with
      PD3. The anti-tumor activity of this polysaccharide after denaturation
      renaturation treatment was further investigated. Both PD3 and RPD3 showed no
      direct cytotoxicity against S-180 cells in vitro but behaved anti-tumor activity
      in vivo. Meanwhile, RPD3 in high-dose group showed much higher anti-tumor
      activity than that of PD3, suggesting that the denaturation-renaturation
      treatment improved the bioactivity of the polysaccharide from D. indusiata.

PMID- 23973498
TI  - Doxorubicin-chitin-poly(caprolactone) composite nanogel for drug delivery.
AB  - In this work, we developed a pH responsive chitin-poly(caprolactone) composite
      nanogels (chitin-PCL CNGs) system for non-small cell lung cancer (NSCLC). A
      hydrophilic drug, doxorubicin (Dox) was loaded in Chitin-PCL CNGs (Dox-chitin-PCL
      CNGs). Both control and drug loaded systems were analyzed by DLS, SEM, FTIR and
      TG/DTA. The size ranges of the control composite nanogels and their drug loaded
      counterparts were found to be 70 +/- 20 and 240 +/- 20 nm, respectively. The
      control chitin-PCL CNGs and Dox-chitin-PCL CNGs showed higher swelling and
      degradation in acidic pH. Drug entrapment efficiency and in-vitro drug release
      studies were carried out and showed a higher drug release at acidic pH compared
      to neutral pH. Cellular internalization of the nanogel systems was confirmed by
      fluorescent microscopy. Dox-Chitin-PCL CNGs showed dose dependent cytotoxicity
      toward A549 (adenocarcinomic human alveolar basal epithelial cells) cancer cells.
      Furthermore, the results of in-vitro hemolytic assay and coagulation assay
      substantiate the blood compatibility of the system. These results indicate that
      chitin-PCL CNGs is a novel carrier for delivery of anticancer drugs.

PMID- 23973499
TI  - Granzyme M as a novel effector molecule for human cytolytic fusion proteins: CD64
      specific cytotoxicity of Gm-H22(scFv) against leukemic cells.
AB  - Immunotoxins are promising targeted therapeutic agents comprising an antibody
      based ligand that specifically binds to diseased cells, and a pro-apoptotic
      protein. Toxic components from bacteria or plants can trigger a neutralizing
      immune response, so that human effector molecules are more suitable. In this
      context, the protease granzyme B has been successfully tested in cytotoxicity
      assays against different cancer cells in vitro and in vivo. Our aim here was to
      introduce granzyme M as an alternative and novel component of human cytolytic
      fusion proteins. We fused it to the humanized single-chain antibody fragment
      (scFv) H22 which specifically binds to CD64, an FcgammaRI receptor overexpressed
      on activated myeloid cells and leukemic cells. We show that the humanized
      cytolytic fusion protein Gm-H22(scFv) specifically targets the acute myeloid
      leukemia cell line HL60 in vitro and is cytotoxic with an IC50 between 1.2 and
      6.4 nM. These findings were confirmed ex vivo using leukemic primary cells from
      patients, which were killed by granzyme M despite the presence of the granzyme B
      inhibitor serpin B9. In conclusion, granzyme M is a promising new cell-death
      inducing component for hCFPs because it specifically and efficiently kills target
      cells when fused to a targeting component.

PMID- 23973500
TI  - The epidemiology of hepatitis B virus infection in HIV-infected and HIV
      uninfected pregnant women in the Western Cape, South Africa.
AB  - OBJECTIVES: Persistent hepatitis B virus (HBV) infection is a major cause of
      morbidity and mortality in sub-Saharan Africa. The HIV epidemic has the potential
      to affect its biology. Immunisation protocols established in the pre-HIV era are
      based upon data showing predominantly horizontal infant transmission. This study
      aimed to determine whether HIV co-infection will change the epidemiology of HBV
      both by increasing infectivity and by favouring the escape of viruses bearing
      phenotypically altered HBsAg. METHODS: This retrospective cross-sectional study
      used antenatal samples from the 2008 Antenatal Sentinel HIV and Syphilis
      Prevalence Survey in the Western Cape, South Africa. All HIV-infected women were
      age and race-matched to HIV-uninfected women. Samples were tested for serological
      markers of HBV and HDV infection. HBV viral load, consensus sequencing and
      genotyping were performed. Luminex technology was used to determine HBsAg
      phenotype. All samples from HIV-infected women were tested for traces of
      antiretroviral drugs by mass spectrometry. RESULTS: This study showed a trend
      toward loss of immune control of HBV in HIV-infected women with 3.4% of samples
      containing HBsAg, 18.9% contained HBeAg. In contrast, 2.9% of samples from HIV
      uninfected women contained HBsAg and 17.1% of these HBeAg. The median HBV load in
      the HIV-infected group was 9.72*10(7)IU/ml and in the HIV-uninfected group
      1.19*10(6)IU/ml. Genotyping showed 63/68 samples belonged to genotype A and the
      remainder genotype D. Mutations in the precore region were found in 35% and 33%
      of samples from HIV-infected and HIV-uninfected respectively. Although no major
      epitope ablation was found, marked variation in HBsAg profiles in HIV-infected
      group was demonstrated. No HDV infection was detected. CONCLUSION: HIV-HBV co
      infected women exhibit a degree of immune escape. One in six HBV-infected
      pregnant women, irrespective of HIV status is HBeAg seropositive. HBV
      immunization of newborns in sub-Saharan Africa should be implemented.

PMID- 23973501
TI  - Perceptions of inpatient rehabilitation changes after the Centers for Medicare
      and Medicaid Service 2010 regulatory updates contrasted with actual performance.
AB  - OBJECTIVES: To compare and contrast subjective perceptions with objective
      compliance of the impact of the 2010 Centers for Medicare and Medicaid Service
      updates of the Medicare Benefit Policy Manual. DESIGN OR SETTING: Cross-sectional
      survey. PARTICIPANTS AND METHODS: An electronic survey was sent by the Uniform
      Data System for Medical Rehabilitation to all enrolled inpatient rehabilitation
      facility subscribers (n = 817). The survey was sent April 15, 2011, and responses
      were tabulated if they were received by May 15, 2011. MAIN OUTCOME MEASUREMENTS:
      Comparing and contrasting of the subjective perception to objective evaluation
      and/or compliance with the Medicare Benefit Policy Manual on case mix index,
      length of stay, admissions by diagnostic category as well as perception of
      preadmission screening, postadmission evaluation, plan of care, and
      interdisciplinary conferencing. RESULTS: Twenty-five percent of the 817
      facilities responded, for a total of 209 responses. Complete data were present in
      148 of the respondents. For most diagnostic categories, perception of change did
      not mirror reality of change; neither did the perception between change in case
      mix index and length of stay. Perception did match reality in stroke and multiple
      trauma cases; respondents perceived an increase in admissions for the 2
      impairments, and there was an overall increase in reality. CONCLUSION: Comparison
      with actual data identified that gaps exist between diagnostic category
      perceptions and actual diagnostic category admission performance. Regulations
      such as the 75%-60% rule and audit focus on non-neurologic conditions as well as
      actual inpatient rehabilitation facility program payment reports may have
      influenced respondents perceptions to change associated with the Medicare Benefit
      Policy Manual modifications. This disparity between perception and actual data
      may have implications for programmatic planning, forecasting, and resource
      allocation.

PMID- 23973502
TI  - Nutrition and eating behavior in patients with chronic pain receiving long-term
      opioid therapy.
AB  - OBJECTIVE: To assess eating behavior and nutrient intake in a group of patients
      who were diagnosed with chronic pain and received long-term opioid analgesic
      therapy. DESIGN: A descriptive, exploratory study with a convenience sample.
      SETTING: An outpatient pain rehabilitation center. PARTICIPANTS: Patients
      diagnosed with chronic pain who received long-term opioid analgesic therapy (N =
      50). MAIN OUTCOME MEASUREMENTS: Body mass index, the Food Frequency Questionnaire
      developed by the Nutrition Assessment Shared Resource of Fred Hutchinson Cancer
      Research Center, and the Eating Behavior Inventory. RESULTS: Of 50 participants,
      14 (28%) and 22 (44%) were found to be overweight and obese, respectively. Mean
      (+/-SD) daily caloric intake (kcal) was 2008.5 +/- 926.0 among men and 1694.8 +/-
      672.4 among women. Daily mean (+/-SD) consumption of fruit and vegetable
      servings, calculated with the summation method, was found to be 1.8 +/- 1.1 and
      1.9 +/- 1.5, respectively. Our patient sample showed the following mean (+/-SD)
      daily intake of the following substances: added sugars (g), 74.4 +/- 43.0; fiber
      (g), 17.3 +/- 7.5; cholesterol (mg), 266.5 +/- 234; saturated fat (g), 25.8 +/-
      16.8; omega-3 fatty acids (g), 1.6 +/- 0.99; trans-fatty acids (g), 2.7 +/- 1.7;
      sodium (mg), 2868.5 +/- 1388.1; caffeine (mg), 199.9 +/- 160.8; alcohol (g), 1.6
      +/- 0.5; vitamin D (IU), 244 +/- 208; and calcium (mg), 1111.7 +/- 672.1. The
      mean (+/-SD) score as calculated by the Eating Behavior Inventory was 74.9 +/-
      9.1. CONCLUSIONS: Obesity, deficient nutrient intake, and poor eating behavior
      were highly prevalent in our sample of patients with chronic pain who underwent
      long-term opioid therapy. Larger prospective studies are necessary to assess the
      eating behavior of patients with chronic pain who are treated with or without
      opioid analgesics.

PMID- 23973503
TI  - Risk factors for discharge to an acute care hospital from inpatient
      rehabilitation among stroke patients.
AB  - OBJECTIVE: To identify medical and functional health risk factors for being
      discharged directly to an acute-care hospital from an inpatient rehabilitation
      facility among patients who have had a stroke. DESIGN: Retrospective cohort
      study. SETTING: Academic medical center. PARTICIPANTS: A total of 783 patients
      with a primary diagnosis of stroke seen from 2008 to 2012; 60 were discharged
      directly to an acute-care hospital and 723 were discharged to other settings,
      including community and other institutional settings. METHODS OR INTERVENTIONS:
      Logistic regression analysis. MAIN OUTCOME MEASUREMENTS: Direct discharge to an
      acute care hospital compared with other discharge settings from the inpatient
      rehabilitation unit. RESULTS: No significant differences in demographic
      characteristics were found between the 2 groups. The adjusted logistic regression
      model revealed 2 significant risk factors for being discharged to an acute care
      hospital: admission motor Functional Independence Measure total score (odds ratio
      0.97, 95% confidence interval 0.95-0.99) and enteral feeding at admission (odds
      ratio 2.87, 95% confidence interval 1.34-6.13). The presence of a Centers for
      Medicare and Medicaid-tiered comorbidity trended toward significance. CONCLUSION:
      Based on this research, we identified specific medical and functional health risk
      factors in the stroke population that affect the rate of discharge to an acute
      care hospital. With active medical and functional management, early
      identification of these critical components may lead to the prevention of stroke
      patients from being discharged to an acute-care hospital from the inpatient
      rehabilitation setting.

PMID- 23973504
TI  - Comparison of autologous conditioned plasma injection, extracorporeal shockwave
      therapy, and conventional treatment for plantar fasciitis: a randomized trial.
AB  - OBJECTIVES: To evaluate the efficacy of autologous conditioned plasma (ACP)
      compared with extracorporeal shockwave (ESWT) and conventional treatments for
      plantar fasciitis. DESIGN: Randomized trial. SETTING: Sports medicine center in a
      tertiary care hospital. PATIENTS: Fifty-four subjects (age range, 29-71 years)
      with unilateral chronic plantar fasciitis with more than 4 months of symptoms.
      METHODS: Subjects randomized to 3 groups: 19 to ACP and conventional treatment
      (ACP group), 19 to ESWT and conventional treatment (ESWT group), and 16 to
      conventional treatment alone. Conventional treatment included stretching
      exercises and orthotics if indicated. MAIN OUTCOME MEASUREMENTS: Outcomes were
      pain-Visual Analog Scale (VAS), American Orthopaedic Foot and Ankle Society
      (AOFAS) ankle-hindfoot scale, and ultrasound plantar fascia thickness assessed at
      baseline before treatment and at 1 month, 3 months, and 6 months after treatment.
      RESULTS: VAS, AOFAS ankle-hindfoot scale, and plantar fascia thickness improved
      in all groups. Significant VAS pain score improvements in the ACP group compared
      with conventional treatment at month 1 (P = .037) and for the ESWT group compared
      with conventional treatment at months 1, 3, and 6 (P = .017, P = .022, and P =
      .042). The AOFAS ankle-hindfoot scale score improved in the ACP group at months 3
      and 6 (P = .004 and P = .013) and, for the ESWT group, at months 1 and 3 (P =
      .011 and P = .003) compared with conventional treatment. Significant improvements
      in plantar fascia thickness were seen in the ACP group at months 1 and 3 compared
      with conventional treatments (P = .015 and P = .014) and at months 3 and 6
      compared with the ESWT group (P = .019 and P = .027). No adverse events reported.
      CONCLUSIONS: Treatment of plantar fasciitis with ACP or ESWT plus conventional
      treatments resulted in improved pain and functional outcomes compared with
      conventional treatment alone. There was no significant difference between ACP and
      ESWT in terms of VAS and AOFAS ankle-hindfoot scale improvements, although the
      ACP group demonstrated greater reductions in plantar fascia thickness.

PMID- 23973505
TI  - Behavioral predictors of outpatient mental health service utilization within 6
      months after traumatic brain injury in adolescents.
AB  - OBJECTIVES: To characterize utilization of mental health services and determine
      the ability of a behavior problem and clinical functioning assessment to predict
      utilization of such services within the first 6 months after moderate and severe
      traumatic brain injury in a large cohort of adolescents. DESIGN: Multicenter
      cross-sectional study. SETTING: Outpatient setting of 4 tertiary pediatric
      hospitals, 2 tertiary general medical centers, and 1 specialized children's
      hospital. PARTICIPANTS: Adolescents age 12-17 years (n = 132), 1-6 months after
      moderate-to-severe traumatic brain injury. METHODS: Logistic regression was used
      to determine the association of mental health service utilization with clinical
      functioning as assessed by the Child and Adolescent Functional Assessment Scale
      and behavior problems assessed by the Child Behavioral Checklist. MAIN OUTCOME
      MEASUREMENT: Mental health service utilization measured by the Service Assessment
      for Children and Adolescents. RESULTS: Behavioral or functional impairment
      occurred in 37%-56%. Of the total study population, 24.2% reported receiving
      outpatient mental health services, 8.3% reported receiving school services, and
      28.8% reported receiving any type of mental health service. Use of any (school or
      outpatient) mental health service was associated with borderline to impaired
      total Child and Adolescent Functional Assessment Scale (odds ratio 3.50 [95%
      confidence interval, 1.46-8.40]; P < .01) and the Child Behavioral Checklist
      Total Competence (odds ratio 5.08 [95% confidence interval, 2.02-12.76]; P <
      .01). CONCLUSIONS: A large proportion of participants had unmet mental health
      needs. Both the Child and Adolescent Functional Assessment Scale and the Child
      Behavioral Checklist identified individuals who would likely benefit from mental
      health services in outpatient or school settings. Future research should focus on
      methods to ensure early identification by health care providers of adolescents
      with traumatic brain injury in need of mental health services.

PMID- 23973506
TI  - Work as a street vendor, associated traffic-related air pollution exposures and
      risk of adverse pregnancy outcomes in Accra, Ghana.
AB  - BACKGROUND: Street vending, a dominant occupation in urban areas of developing
      countries exposes the vendors to several environmental pollutants. We
      investigated whether work as street vendor impairs foetal growth and shortens
      gestational duration, and evaluated to what extent exposure to traffic-related
      air pollution is responsible for these adverse effects. METHODS: A cross
      sectional study was conducted among mothers and their newborns accessing
      postnatal services at the Korle Bu Teaching Hospital in Accra, Ghana in 2010,
      focusing on 105 street vendors and a reference group of 281 mothers. We
      categorized exposure to traffic-related air pollution on the basis of street
      vending activity patterns and traffic density in the working area. RESULTS:
      Multivariate linear regression analysis adjusting for age, social class, marital
      status and gravidity of mothers, sex of neonate, and indoor air pollution,
      indicated a 177 g (95% CI: 324, 31) reduction in birth weight among street
      vendors. Sensitivity analysis performed by restricting the analysis to term
      births showed further reductions in birth weight. Generalized linear models
      adjusting for confounders indicated a 35% (risk ratio (RR)=1.35; 95% CI: 0.87,
      2.12) increased risk of LBW, albeit statistically not significant. LBW risk
      increased in the sensitivity analysis but was also not statistically significant.
      The risk of PTB was not associated with street vending (RR=1.03; 95% CI: 0.67,
      1.58). The exposure-response relations observed were not consistent. Moderate
      activity patterns and high traffic density jointly was associated with a
      statistically significant 84% (RR=1.84; 95% CI: 1.05, 3.24) increased risk of
      LBW. CONCLUSION: Street vending during pregnancy is a determinant of average
      foetal growth and risk of LBW. More research is required to further quantify
      their effects on pregnancy outcomes and safeguard maternal and perinatal health
      in developing countries.

PMID- 23973507
TI  - Beyond direct impact: evidence synthesis towards a better understanding of
      effectiveness of environmental health interventions.
AB  - Systematic reviews are a cornerstone of evidence-based public health, and there
      is much discussion on how this method may need to be modified to do justice to
      complex interventions, such as environmental health interventions. This paper
      asserts that intervention effectiveness is influenced by variability in five
      distinct layers--direct (intrinsic) impact, user compliance, delivery,
      programming and policy measures--which are embedded in the broader geographical,
      socio-economic, political and cultural context. The multi-component, multi
      sectoral nature of most environmental health interventions results in a complex
      relationship between these layers of influence, involving systemic interactions.
      As illustrated with examples, understanding environmental health interventions
      critically relies on considering all of these layers. These distinct layers of
      influence can serve as a framework towards the comprehensive analysis of
      environmental health interventions in systematic reviews, drawing on quantitative
      and qualitative methods and a variety of disciplines.

PMID- 23973508
TI  - Effects of mycophenolic acid-glucosamine conjugates on the base of kidney
      targeted drug delivery.
AB  - Mycophenolic acid has played an important role in treating immunosuppression and
      autoimmune diseases. Nevertheless, the agent needs a high dosage in treatment,
      following some side effects. To tackle this problem, in this study, mycophenolic
      acid-glucosamine conjugate (MGC), modified by 2-glucosamine, was synthesized to
      achieve kidney targeting and improved drug efficacy with a lower dosage. (1)H
      NMR, (13)C NMR and HRMS spectroscopy were used to verify the conjugate whose
      stability was good in vitro. The transport of MGC by human proximal renal tubular
      epithelial HK-2 cells was temperature-, time-, concentration-dependent and
      saturable, suggesting the involvement of carrier-mediated uptake. In addition,
      the cellular uptake of MGC dropped substantially with the inhibition of megalin
      receptor. The specific tissue distribution indicated the commendable renal
      targeting capability of MGC. The concentration of MGC was improved in the kidney
      except for other tissues, about 6.76 times higher than that of MPA. Further, the
      bioavailability of MGC in plasma decreased as compared with mycophenolic acid.
      Moreover, therapeutic effect of MGC was enhanced significantly compared with MPA
      in the acute kidney injury model. All the findings suggested the potential of
      mycophenolic acid-glucosamine conjugate in kidney targeted drug delivery. 

PMID- 23973509
TI  - Influence of borneol and muscone on geniposide transport through MDCK and MDCK
      MDR1 cells as blood-brain barrier in vitro model.
AB  - The objective of this study was (1) to characterize geniposide transport through
      MDCK and MDCK-MDR1 cell lines to confirm its transport mechanism and (2) to
      evaluate the effect of borneol and muscone as enhancers of geniposide transport
      in the BBB models so as to explore the enhancement mechanism. Transport studies
      of geniposide were performed in both directions, from apical to basolateral and
      from basolateral to apical sides. Drug concentrations were analyzed by HPLC.
      Geniposide showed relatively poor absorption in MDCK and MDCK-MDR1 cells,
      apparent permeability coefficients ranging from 0.323*10(-6) to 0.422*10(-6)
      cm/s. The in vitro experiments showed that geniposide transport in both
      directions was not concentration dependent and saturable, indicating purely
      passive diffusion. The efflux ratio of geniposide was less than 2 in the two cell
      models, which suggested that geniposide was not P-gp substrates. Geniposide
      transport in both directions significantly increased when co-administrated with
      increasing concentrations of borneol and muscone. Actin staining results
      indicated that borneol and muscone increased geniposide transport in the BBB
      models may attribute to disassembly effect on tight junction integrity.

PMID- 23973510
TI  - Pectinase hydrolysis of Dendrobium huoshanense polysaccharide and its effect on
      protein nonenzymatic glycation.
AB  - The aim of this study was to investigate the inhibitory effects of molecular
      weight alteration of Dendrobium huoshanense polysaccharide on protein
      nonenzymatic glycation. For this purpose, one homogeneous active polysaccharide
      DHPD1 with molecular weight 3.2 kDa was extracted from D. huoshanense. GC
      analysis showed that DHPD1 was mainly composed of glucose, arabinose, galactose
      in a molar ratio of 0.023:1.023:0.021 with a trace of mannose and xylose. In
      order to get DHPD1-derived fragments with different molecular weight, response
      surface methodology was employed to optimize the enzymatic degradation
      conditions. The maximum reducing sugar production (0.399 mg/mL) was obtained
      under an optimal condition including pectinase dosage 126 U/mL, reaction pH 4.46
      and reaction temperature 48  degrees C. By applying this condition, three DHPD1
      derived fragments with different molecular weights were obtained through changing
      the hydrolysis time. Infrared spectroscopy analysis indicated that the backbone
      structure of DHPD1 was not destroyed by pectinase hydrolysis. Monosaccharide
      composition analysis showed that pectinase preferred to liberate glucose from
      DHPD1. The inhibitory action of DHPD1 on protein nonenzymatic glycation reduced
      with the decrease of molecular weight.

PMID- 23973511
TI  - Effect of Zn2+ and temperature on the conformational equilibrium of single
      stranded polyA in neutral solutions.
AB  - Effect of Zn(2+) ions on the conformation of polyA in cacodilic buffer at pH 7
      was investigated by differential UV spectroscopy (DUV) and by thermal
      denaturation. The shapes of the DUV spectra and melting curves suggest a
      transition of polyA into a more ordered "metallized", possibly double-helical
      conformation at Zn(2+) concentrations above 3*10(-5) M. A phase diagram of polyA
      complexes with Zn(2+) was constructed for the temperature range from 20  degrees
      C to 95  degrees C and Zn(2+) concentrations between 10(-5) M and 5*10(-4) M. It
      was found that the transition of a single strand into the "metallized" form is
      possible only if the length of the disordered single-stranded region becomes
      larger than a certain critical value, ranging between 98% and 78% as the metal
      concentration increases from 3*10(-5) to 5*10(-4) M.

PMID- 23973512
TI  - Analysis of outcome using a levator sparing technique of abdominoperineal
      excision of rectum and anus. Cylindrical ELAPE is not necessary in all patients.
AB  - AIMS: Abdominoperineal excision of rectum (APE) for cancer has a higher rate of
      local recurrence with a poorer outcome than stage matched anterior resection. The
      cylindrical excision (ELAPE) has been advocated to reduce local recurrence.
      However, this operation has greater morbidity and requires more post operative
      care. We report our outcomes from a single centre using a levator sparing
      dissection. METHODS: All patients undergoing APE from January 2007-June 2011 were
      evaluated. Case notes operation notes and pathology results were reviewed for
      complications and staging. Follow-up data for survival and recurrence were
      obtained from the cancer registry, imaging and from clinic follow up. RESULTS: Of
      all rectal cancers (n = 361), 43 had APE with curative intent. Median age was
      67(IQR 59-76). Median tumour height was two centimetres from the dentate line
      (IQR 1-3.5 cm). Neoadjuvant chemoradiotherapy was given in 98% of APE resections
      with curative intent. Median post operative hospital stay was 10 days (8-15). At
      a median follow up of 38 months (IQR30-49) for patients undergoing curative
      resection, 2 patients (4.6%) had local recurrence and overall mortality was 18.6%
      (n = 8). CONCLUSION: With adequate neoadjuvant chemoradiotherapy, a levator
      sparing excision of rectum remains a safe option with less morbidity and
      perioperative complications than has been described for ELAPE.

PMID- 23973513
TI  - Prognostic significance of the number of examined lymph nodes in node-negative
      gastric adenocarcinoma.
AB  - AIM: In this study, we investigated the prognostic significance of the number of
      examined lymph nodes in node-negative gastric adenocarcinoma (GC). PATIENTS AND
      METHODS: A total of 1194 node-positive and 1030 node-negative GC patients
      undergoing potentially curative gastrectomy was enrolled in this study. Patients
      were stratified into 3 groups according to the number of examined lymph nodes:
      group 1, <= 15; group 2, 16-25; group 3, >25. RESULTS: Patients with node
      negative GC had significantly favorable survival compared with those with node
      positive. Among patients with node-negative T2-T4 disease, the percentage of
      locoregional relapse was higher in those with <25 examined lymph nodes than in
      those with >= 25 examined lymph nodes. The number of examined lymph nodes
      affected the overall survival rates for patients with node-negative T2-T4 GC but
      not for patients with T1 lesions. Tumor size, tumor location, the number of
      examined lymph nodes, T status, and the presence of perineural invasion were
      significant prognostic factors as determined by multivariate analysis in node
      negative GC. CONCLUSIONS: No survival benefit of examining >= 15 lymph nodes was
      noted for patients with node-negative T1 GC. Extensive lymphadenectomy in
      patients with node-negative T2-T4 lesions in whom the number of examined lymph
      nodes was >25 had favorable survival.

PMID- 23973514
TI  - Reasons for readmission after carotid endarterectomy.
AB  - OBJECTIVE: With increasing oversight of postoperative outcomes with the Patient
      Protection and Affordable Care Act, the reduction of readmissions is necessary to
      avoid financial penalties. This article provides a multi-institutional,
      multivariate analysis of the pre- and postoperative patient factors associated
      with readmission after carotid endarterectomy (CEA). METHODS: Using the National
      Surgical Quality Improvement Program from 2011, we considered 8456 patients. The
      primary outcome variable was 30-day unplanned readmission. Multiple logistic
      regression was used, and we controlled for preoperative demographic variables,
      comorbidities and clinical characteristics, and postoperative medical and
      surgical complications. RESULTS: Patients with CEA had a 6.0% unplanned
      readmission rate. The most common comorbidities in the readmitted patients
      included hypertension, diabetes, and bleeding disorder. Risk-adjusted multiple
      regression indicated that preoperative bleeding disorder (odds ratio [OR] 1.62),
      diabetes (OR 1.46), history of a cerebrovascular accident/stroke (OR 1.46), and
      increasing age (OR 1.01) were statistically significant predictors for
      readmission. Postoperatively, surgical-site infection (OR 21.90), myocardial
      infarction (OR 10.35), sepsis/septic shock (OR 7.79), cerebrovascular
      accident/stroke (OR 6.58), pneumonia (OR 4.37), and urinary tract infection (OR
      3.21) were associated with a greater rate of readmission. CONCLUSIONS:
      Readmission after CEA occurs at a comparatively high rate. Preoperative bleeding
      disorders, diabetes, cerebrovascular accidents, and age and postoperative
      surgical-site infection, myocardial infarction, sepsis/septic shock, pneumonia,
      and cerebrovascular accident were associated with readmission. These findings may
      help guide the surgical management of patients and prevent costly readmissions.

PMID- 23973515
TI  - Acute chiasmal abscess resulting from perineural extension of invasive sino
      orbital aspergillosis in an immunocompetent patient.
AB  - OBJECTIVE: Intracranially invasive sino-orbital aspergillosis is a rare entity
      seen predominantly in immunocompromised individuals. We report a unique case of
      an acute chiasmal abscess resulting from perineural extension of an indolent
      invasive sino-orbital aspergillosis in an immunocompetent patient. CASE
      DESCRIPTION: A 61-year-old healthy Ukrainian man presented with severe left retro
      orbital pain and a gradual ipsilateral monocular vision loss with rapid
      progression to a contralateral temporal visual field cut. He was found to have an
      intracranially invasive sino-orbital Aspergillus fumigatus infection with
      perineural extension along the optic nerve complicated by an acute chiasmal
      abscess. RESULTS: The patient was managed with surgical debridement and adjuvant
      antifungal chemotherapy. The patient's life and vision were preserved.
      CONCLUSIONS: The case demonstrates that it is possible to successfully control
      advanced intracranial aspergillosis with tissue-sparing surgery and adjuvant
      antifungal chemotherapy in immunocompetent individuals.

PMID- 23973516
TI  - Do young patients with renal cell carcinoma feature a distinct outcome after
      surgery? A comparative analysis of patient age based on the multinational CORONA
      database.
AB  - PURPOSE: We analyzed the distinct clinicopathological features and prognosis of
      patients with renal cell carcinoma age 40 years or less compared to a reference
      group of patients 60 to 70 years old. MATERIALS AND METHODS: Overall 2,572
      patients retrieved from a multicenter international database comprised of 6,234
      patients with surgically treated renal cell carcinoma were included in this
      retrospective study. Clinical and histopathological features of 297 patients 40
      years old or younger (4.8%) were compared to those of 2,275 patients (36.5%) 60
      to 70 years old, who served as the reference group. Median followup was 59
      months. The impact of young age and further parameters on disease specific
      mortality and all cause mortality was evaluated by multivariate Cox proportional
      hazards regression analyses. RESULTS: Young patients more frequently underwent
      nephron sparing surgery (27% vs 20%, p = 0.008) and regional lymph node
      dissection compared to older patients (38% vs 32%, p = 0.025). Organ confined
      tumor stage (81% vs 70%, p <0.001), smaller tumor diameter (4.5 vs 4.7 cm, p =
      0.014) and chromophobe subtype (10% vs 4%, p <0.001) were significantly more
      frequent in young patients. On multivariate analysis older patients had a higher
      disease specific (HR 2.21, p <0.001) and all cause mortality (HR 3.05, p <0.001).
      The c indices for the Cox models were 0.87 and 0.78, respectively. However,
      integration of the variable age group did not significantly increase the
      predictive accuracy of the disease specific and all cause mortality models.
      CONCLUSIONS: Young patients with renal cell carcinoma (40 years old or younger)
      have significantly different frequencies of clinical and histopathological
      features, and a significantly lower all cause and disease specific mortality
      compared to patients 60 to 70 years old.

PMID- 23973517
TI  - Comprehensive evaluation of anterior elevate system for the treatment of anterior
      and apical pelvic floor descent: 2-year followup.
AB  - PURPOSE: The Elevate(r) Anterior and Apical Prolapse Repair System is a
      polypropylene mesh that is anchored through sacrospinous ligament and obturator
      fascia fixation points. We present a comprehensive evaluation of this prolapse
      repair system through 2 years with a focus on safety, operative characteristics,
      and anatomical, subjective and quality of life outcomes. MATERIALS AND METHODS: A
      total of 42 women underwent repair of stage II or greater anterior/apical
      compartment prolapse using the repair system, of whom 2 were lost to followup.
      Anatomical outcomes were assessed using POP-Q (Pelvic Organ Prolapse
      Quantification) staging. Subjective and quality of life outcomes were assessed by
      the validated ICIQ (International Consultation on Incontinence Questionnaire)-VS
      (Vaginal Symptoms), ICIQ-FLUTS (Female Lower Urinary Tract Symptoms) and IIQ-7
      (Incontinence Impact Questionnaire-7). Additional outcomes included a 3-day
      bladder diary and cough test with outcomes assessed preoperatively, at 6 weeks,
      and at 1 and 2 years. RESULTS: Mean +/- SD blood loss was 93 +/- 55 cc and mean
      operative time was 58 +/- 27 minutes. POP-Q points Aa, Ba and C improved from
      0.9, 0.8 and -1.3 preoperatively to -2.1, -2.7 and -6.1 cm at 2 years,
      respectively (each p <0.05). Four patients experienced anatomical recurrence,
      which was associated in 2 with symptomatic recurrence on the ICIQ-VS.
      Statistically significant improvements in the ICIQ-VS, ICIQ-FLUTS and IIQ-7 were
      seen throughout followup. Adverse events included leg pain, vaginal exposure and
      urinary retention in 1, 2 and 5 patients, respectively. CONCLUSIONS: The Elevate
      Anterior and Apical Prolapse Repair System was associated with good anatomical
      restoration and significant improvements in validated symptom and quality of life
      indexes through 2 years of assessments. Our experience suggests that the system
      is a safe, effective surgical procedure in appropriately selected patients. Long
      term followup is important, given the FDA (Food and Drug Administration) warning
      regarding the use of surgical mesh in the repair of pelvic organ prolapse.

PMID- 23973518
TI  - The effect of restaging transurethral resection on recurrence and progression
      rates in patients with nonmuscle invasive bladder cancer treated with
      intravesical bacillus Calmette-Guerin.
AB  - PURPOSE: We determined whether restaging resection before initiating induction
      intravesical bacillus Calmette-Guerin improves the recurrence-free rate in
      patients with high risk nonmuscle invasive bladder cancer. MATERIALS AND METHODS:
      We retrospectively analyzed data on 1,021 patients treated at our institution
      with intravesical bacillus Calmette-Guerin for nonmuscle invasive high risk
      bladder cancer. All patients underwent a second resection except those already
      receiving bacillus Calmette-Guerin at the time of initial consultation and those
      who refused restaging resection. All patients were assessed every 3 to 12 months
      for a minimum of 5 years. Univariate and multivariate regression was used to
      identify predictors of 5-year recurrence. RESULTS: Restaging transurethral
      resection was performed in 894 patients (87.5%). At restaging resection viable
      tumor was found in 496 patients (55.5%). At 3 months patients with a single
      resection had a 44.3% recurrence rate compared to 9.6% in those with restaging
      resection (p <0.01). On multivariate analysis a single transurethral resection
      was the only predictor of recurrence at 5 years (OR 2.1, 95% CI 1.3-3.3, p =
      0.01). Time to recurrence in patients with a single resection was significantly
      shorter than in those with restaging resection (median 22 vs 36 months, p
      <0.001). CONCLUSIONS: Failure to repeat resection before initiating intravesical
      bacillus Calmette-Guerin therapy for high risk nonmuscle invasive bladder cancer
      significantly increases the risk of recurrence. Therefore, we believe that
      restaging resection should be performed before initiating bacillus Calmette
      Guerin therapy in all patients with high risk nonmuscle invasive bladder cancer.

PMID- 23973519
TI  - Urinary NGF, TGF-beta1, TIMP-2 and bladder wall thickness predict neurourological
      findings in children with myelodysplasia.
AB  - PURPOSE: Dimercapto-succinic acid scintigraphy and urodynamic studies are gold
      standards to evaluate renal scarring and neurogenic bladder dysfunction,
      respectively. We sought to establish the value of bladder wall thickness together
      with urine NGF, TGF-beta1 and TIMP-2 to predict the urodynamic profile and upper
      urinary tract damage in children with myelodysplasia. MATERIALS AND METHODS: A
      total of 80 children with myelodysplasia underwent urodynamic investigation,
      bladder wall thickness measurement and dimercapto-succinic acid scintigraphy with
      basic neurourological evaluation. Two study and 2 control groups were created
      according to presence or absence of renal scarring on dimercapto-succinic acid
      scan (study and control groups 1) and according to detrusor leak point pressure
      greater or less than 40 cm H2O (study and control groups 2). Urine samples were
      analyzed with ELISA. RESULTS: The study population consisted of 44 girls and 36
      boys with a median +/- SD age of 7.2 +/- 3.6 years (range 2 to 17). Study and
      control groups 1 consisted of 35 and 45 children with abnormal and normal
      dimercapto-succinic acid scan findings, respectively. Study and control groups 2
      included 30 and 50 children with detrusor leak point pressure greater and less
      than 40 cm H2O, respectively. Bladder wall thickness and urinary levels of TGF
      beta1, NGF and TIMP-2 were significantly increased in both study groups compared
      to controls. CONCLUSIONS: Urine markers and bladder wall thickness measurement
      may predict urinary tract impairment in children with myelodysplasia. Such
      markers may differentiate at risk patients with either renal scarring or high
      detrusor leak point pressure, and decrease the need for urodynamics and renal
      scintigraphy.

PMID- 23973520
TI  - Effects of allogeneic bone marrow derived mesenchymal stromal cell therapy on
      voiding function in a rat model of Parkinson disease.
AB  - PURPOSE: Cellular therapy induced transient urodynamic improvement in a rat model
      of Parkinson disease in which bladder dysfunction was noted after unilateral
      injection of 6-hydroxydopamine into the medial forebrain bundle. We sought to
      prolong the effect by injecting allogeneic rat bone marrow mesenchymal stromal
      cells before and after microencapsulation into the substantia nigra pars
      compacta. MATERIALS AND METHODS: Female rats underwent unilateral stereotactic
      injection of 6-hydroxydopamine in the medial forebrain bundle. Injection was
      performed in the ipsilateral substantia nigra pars compacta using vehicle alone
      or vehicle with nonmicroencapsulated or microencapsulated rat bone marrow derived
      mesenchymal stromal cells. Rats were evaluated by cystometry 7, 14, 28 and 42
      days after treatment. Brains were extracted for immunostaining. RESULTS: At 42
      days the nonmicroencapsulated group had lower threshold and intermicturition
      pressure, spontaneous activity and AUC than vehicle treated animals. Rats that
      received microencapsulated cells had lower threshold pressure at 28 days and
      lower spontaneous activity at 42 days than vehicle treated rats.
      Microencapsulated and nonmicroencapsulated rat bone marrow derived mesenchymal
      stromal cells were noted in the substantia nigra pars compacta up to 42 days
      after transplantation. At 42 days tyrosine hydroxylase positive neurons were more
      numerous in the substantia nigra pars compacta of the nonmicroencapsulated group,
      followed by the microencapsulated and vehicle treated groups. CONCLUSIONS:
      Urodynamic effects of the 6-hydroxydopamine lesion persisted up to 42 days after
      vehicle injection. Transplantation of nonmicroencapsulated rat bone marrow
      derived mesenchymal stromal cells improved urodynamic pressure by 42 days after
      treatment more markedly than microencapsulated cells. This was associated with
      more tyrosine hydroxylase positive neurons in the treated substantia nigra pars
      compacta of the nonmicroencapsulated group, suggesting that functional
      improvement requires a juxtacrine effect.

PMID- 23973521
TI  - An endogenous pain control system is altered in subjects with interstitial
      cystitis.
AB  - PURPOSE: Multiple studies have demonstrated that in healthy subjects, painful
      stimuli applied to one part of the body inhibit pain sensation in other parts of
      the body, a phenomenon referred to as conditioned pain modulation. Conditioned
      pain modulation is related to the presence of endogenous pain control systems.
      Studies have demonstrated deficits in conditioned pain modulation associated
      inhibition in many but not all chronic pain disorders. In this study we determine
      whether conditioned pain modulation is altered in subjects with interstitial
      cystitis/bladder pain syndrome. MATERIALS AND METHODS: Female subjects with and
      without the diagnosis of interstitial cystitis/bladder pain syndrome were studied
      psychophysically using quantitative cutaneous thermal, forearm ischemia and ice
      water immersion tests. Conditioned pain modulation was assessed by quantifying
      the effects of immersion of the hand in ice water (conditioning stimulus) on
      threshold and tolerance of cutaneous heat pain (test stimulus) applied to the
      contralateral lower extremity. RESULTS: The conditioned pain modulation responses
      of the subjects with interstitial cystitis/bladder pain syndrome were
      statistically different from those of healthy control subjects for cutaneous
      thermal threshold and tolerance measures. Healthy control subjects demonstrated
      statistically significant increases in thermal pain tolerance whereas subjects
      with the diagnosis of interstitial cystitis/bladder pain syndrome demonstrated
      statistically significant reductions in thermal pain tolerance. CONCLUSIONS: An
      endogenous pain inhibitory system normally observed with conditioned pain
      modulation was altered in subjects with interstitial cystitis/bladder pain
      syndrome. This finding identifies interstitial cystitis/bladder pain syndrome as
      similar to several other chronic pain disorders such as fibromyalgia and
      irritable bowel syndrome, and suggests that a deficit in endogenous pain
      inhibitory systems may contribute to such chronic pain disorders.

PMID- 23973522
TI  - Effect of fesoterodine in vulnerable elderly subjects with urgency incontinence:
      a double-blind, placebo controlled trial.
AB  - PURPOSE: We evaluated the efficacy and safety of flexible dose fesoterodine in
      medically complex vulnerable elderly subjects with urgency urinary incontinence.
      MATERIALS AND METHODS: In this 12-week, randomized, double-blind, flexible dose,
      placebo controlled trial, subjects were community dwelling men and women 65 years
      old or older. Subjects had scores of 3 or more on the VES-13 (Vulnerable Elders
      Survey) and 20 or more on the MMSE (Mini-Mental State Examination), and 2 to 15
      urgency urinary incontinence episodes and 8 or more micturitions per 24 hours on
      3-day baseline diaries. Subjects randomized to fesoterodine received 4 mg once
      daily for 4 weeks and could then increase to 8 mg based on discussion with the
      investigator. Subjects receiving 8 mg could decrease the dose to 4 mg at any time
      (sham escalation and de-escalation for placebo). The primary outcome measure was
      change in daily urgency urinary incontinence episodes. Secondary outcomes
      included changes in other diary variables and patient reported quality of life
      measures. Safety evaluations included self-reported symptoms and post-void
      residual volume. RESULTS: A total of 562 patients were randomized (mean age 75
      years, 50.4% age 75 years or greater). Subjects had high rates of comorbidities,
      polypharmacy and functional impairment. At week 12 the fesoterodine group had
      significantly greater improvements in urgency urinary incontinence episodes per
      24 hours (-2.84 vs -2.20, p = 0.002) and most other diary variables and quality
      of life, as well as a higher diary dry rate (50.8% vs 36.0%, p = 0.002). Adverse
      effects were generally similar to those of younger populations including risk of
      urinary retention. CONCLUSIONS: To our knowledge this is the first antimuscarinic
      study in a community based, significantly older, medically complex elderly
      population with urgency urinary incontinence. Flexible dose fesoterodine
      significantly improved urgency urinary incontinence episodes and other outcomes
      vs placebo, and was generally well tolerated.

PMID- 23973523
TI  - The complexity of medicinal plants: the traditional Artemisia annua formulation,
      current status and future perspectives.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua has a long tradition of use for
      the treatment of intermittent fevers which we now relate to malarial infections.
      The active principle artemisinin has been isolated from Artemisia annua and today
      forms the backbone of the global fight against malaria. The traditionally
      prepared Artemisia annua formulation is however still being used on a global
      scale for the treatment of malaria, and it is claimed that its action is superior
      to the single purified drug. Artemisia annua is therefore on the forefront of the
      heated debate between the single drug-single target approach of western based
      medicine and the holistic approach of traditional medicinal systems. This review
      aims to highlight the complexities we face in the general study of medicinal
      plants at the hand of three levels of complexity. These levels consist of (a) the
      chemistry of the medicinal plant, (b) the influence of the preparation method on
      the chemistry of the final formulation and (c) the influence of metabolism on the
      chemistry of the formulation. We also aim to provide an up-to-date report on all
      scientific work that has been conducted and published in English on the
      traditional formulation of Artemisia annua. MATERIALS AND METHODS: All English
      scientific literatures published until the first quarter of 2013 were retrieved
      from well-known scientific databases (Scifinder scholar, Web of Science, PubMed,
      Google scholar) and Non-governmental organisations active in this field were
      consulted. A draft version of this manuscript was sent to the African office of
      the World Health Organisation (WHO), and to the Non-governmental organisations
      "Action Medicine Naturelle" (ANAMED) and "Iwerliewen fir bedreete Volleker -
      Reseau belgo-luxembourgeois pour la valorisation des herbes medicinales" (IFBV
      BELHERB) for comments. RESULTS: Very little scientific work has been conducted on
      the Artemisia annua formulation. The available literature contains many
      discrepancies which are unfortunately selectively being used by the two different
      sides in this debate to further their arguments. On one side of the argument we
      have the low content of artemisinin in Artemisia annua, the low bioavailability
      of artemisinin when the traditional formulation is administered and the high
      levels of recrudescence, which are being emphasised, while on the other side the
      possible role of synergism and prodrugs are being highlighted. This review
      reports that there are still too many gaps in our existing knowledge to provide
      conclusive evidence for either of the two sides of the argument. CONCLUSIONS:
      Much more research is needed into Artemisia annua formulations. We stand to gain
      invaluable knowledge into how traditional medicinal plant works, discover the
      identities of new active compounds (which can be used against other diseases such
      as HIV, diarrhoea, and cancer) and possibly bring both sides of this debate
      closer together.

PMID- 23973524
TI  - Combining molecular docking and 3-D pharmacophore generation to enclose the in
      vivo antigenotoxic activity of naturally occurring aromatic compounds: myricetin,
      quercetin, rutin, and rosmarinic acid.
AB  - Considering the controversial results concerning the antimutagenicity of some
      phenolic compounds recorded in the literature, the antigenotoxic effects of four
      selected phenolic compounds, myricetin, quercetin, rutin, and rosmarinic acid,
      against DNA damage induced by alkylation with ethyl methanesulfonate (EMS), were
      evaluated in Drosophila melanogaster males using the sex-linked recessive lethal
      (SLRL) test. To assess the protective effects against DNA damage, D. melanogaster
      males were exposed to a monofunctional alkylating agent EMS in concentration of
      0.75 ppm, 24 h prior to one of the selected phenolic compounds in the
      concentration of 100 ppm. The possible differences in mechanisms of protection by
      selected compounds were determined by molecular docking, after which structure
      based 3-D pharmacophore models were generated. EMS induced considerable DNA
      damage as shown by significant increase in the frequency of germinative
      mutations. The frequency decreased with high significance (p<0.001***) after post
      treatments with all selected phenolic compounds. Further, docking analysis
      revealed EMS pre-bond conformations against guanine and thymine as a necessary
      condition for alkylation, after which resulting O6-ethylguanine and O4
      ethylthimine were docked into the active site of O6-alkylguanine-DNA
      alkyltransferase to confirm that particular lesions are going to be repaired.
      Finally, myricetin and quercetin protected dealkylated nucleotides from further
      EMS alkylation by forming the strong hydrogen bonds with O6-guanine and O4
      thymine via B ring hydroxyl group (bond lengths lower than 2.5 A). On the other
      side, rutin and rosmarinic acid encircled nucleotides and by fulfilling the EMS
      binding space they made an impermeable barrier for the EMS molecule and prevented
      further alkylation.

PMID- 23973525
TI  - The anthraquinone drug rhein potently interferes with organic anion transporter
      mediated renal elimination.
AB  - Rhein, a major metabolite of the prodrug diacerein and a major component of the
      medicinal herb Rheum sp., is used for its beneficial effects in a variety of
      clinical applications including the treatment of osteoarthritis and diabetic
      nephropathy. The physicochemical properties of rhein are consistent with those of
      known organic anion transporter (OAT) substrates and inhibitors. Therefore, the
      inhibitory effect of rhein on human (h) OAT1, hOAT3, hOAT4, and murine (m) Oat1
      and mOat3 was examined in heterologous cell lines stably expressing each
      transporter in isolation. Rhein was shown to potently inhibit hOAT1 and hOAT3,
      with IC50 estimates in the low nanomolar range (IC50=77.1+/-5.5 nM and 8.4+/-2.5
      nM, respectively), while poor affinity was observed for hOAT4 (IC50>100 MUM).
      Marked species differences were observed with hOAT1 and hOAT3 exhibiting 3- and
      28-fold higher affinity for rhein as compared to their murine orthologs. The
      estimated drug-drug interaction (DDI) indices (>>0.1) indicated a very strong
      potential for clinically relevant, rhein perpetrated DDIs mediated by inhibition
      of hOAT1 (DDI index=5.0; 83% inhibition) and/or hOAT3 (DDI index=46; 98%
      inhibition) transport activity. These results suggested that rhein, from herbal
      medicines and/or prodrug conversion, may significantly impact the dosing,
      efficacy and toxicity (i.e., pharmacokinetics and pharmacodynamics) of co
      administered hOAT1 and/or hOAT3 drug substrates.

PMID- 23973526
TI  - RhoA/ROCK-dependent pathway is required for TLR2-mediated IL-23 production in
      human synovial macrophages: suppression by cilostazol.
AB  - IL-23 is produced by antigen presenting cells and plays critical roles in immune
      response in rheumatoid arthritis. In this study, we investigated whether the
      RhoA/Rho-kinase pathway is required to elevate TLR2-mediated IL-23 production in
      synovial macrophages from patients with rheumatoid arthritis (RA), and then
      examined the suppressive effect of cilostazol on these pathways. IL-23 production
      was elevated by lipoteichoic acid (LTA), a TLR2 ligand, and this elevation was
      more prominent in RA macrophages than in those from peripheral blood of normal
      control. LTA increased the activation of RhoA in association with increased the
      nuclear translocation of NF-kappaB and its DNA-binding activity. Pretreatment of
      RA macrophages with the pharmacological inhibitors exoenzyme C3 (RhoA), Y27632
      (Rho-kinase) or BAY11-7082 (NF-kappaB) inhibited IL-23 production by LTA.
      Inhibition of the RhoA/Rho-kinase pathway by these drugs attenuated NF-kappaB
      activation. Cilostazol suppressed the TLR2-mediated activation of RhoA, decreased
      NF-kappaB activity with down-regulated IL-23 production, and these effects were
      reversed by Rp-cAMPS, as an inhibitor of cAMP-dependent protein kinase. The
      expression of IL-23, which colocalized with CD68+ cells in knee joint of CIA
      mice, was significantly attenuated by cilostazol along with the decreased
      severity of arthritis. Taken together, the RhoA/Rho-kinase pathway signals TLR2
      stimulated IL-23 production in synovial fluid macrophages via activation of NF
      kappaB. Thus it is summarized that cilostazol suppresses TLR2-mediated IL-23
      production by suppressing RhoA pathway via cAMP-dependent protein kinase
      activation.

PMID- 23973527
TI  - Allosteric peptide regulators of chemokine receptors CXCR4 and CXCR7.
AB  - The chemokine CXCL12 and its shared seven-transmembrane receptors CXCR4 and CXCR7
      regulate diseases including cancer, atherosclerosis, autoimmunity, and HIV
      infection, making these molecules promising drug targets. These molecules also
      control key processes in normal development and physiology, suggesting the need
      to selectively modulate CXCR4 and/or CXCR7 functions and signaling to reduce
      potential complications of long-term therapy. We previously identified two
      peptides that functioned as allosteric agonists driving CXCR4-dependent
      chemotaxis, providing key structural information to design a small number of
      additional peptides to investigate determinants of CXCL12 interactions and
      signaling through CXCR4 and CXCR7. In the current study, we show that the
      previously identified peptides only minimally activated CXCR4 signaling through
      the cytosolic adapter protein beta-arrestin 2 and do not initiate signaling to
      ERK1/2. By comparison, peptides with diverse N-terminal amino acid sequences
      effectively activated CXCR7 signaling to beta-arrestin 2. One peptide, designated
      as GSLW based on its N-terminal amino acids, activated CXCR7 signaling and
      potentiated CXCL12-CXCR7 signaling without blocking the scavenger function of
      CXCR7 to internalize CXCL12. These results advance our understanding of CXCR7
      ligand recognition and signaling, and provide structural information to target
      allosteric binding sites on this receptor as chemical probes and potential
      therapeutic agents. 

PMID- 23973529
TI  - Nitrosylhemoglobin in photodynamically stressed human tumors growing in nude
      mice.
AB  - The role of nitric oxide in human tumor biology and therapy has been the subject
      of extensive studies. However, there is only limited knowledge about the
      mechanisms of NO production and its metabolism, and about the role NO can play in
      modern therapeutic procedures, such as photodynamic therapy. Here, for the first
      time, we report the presence of nitrosylhemoglobin, a stable complex of NO, in
      human lung adenocarcinoma A549 tumors growing in situ in nude mice. Using
      electron paramagnetic resonance spectroscopy we show that the level of
      nitrosylhemoglobin increases in the course of photodynamic therapy and that the
      phenomenon is local. Even the destruction of strongly vascularized normal liver
      tissue did not induce the paramagnetic signal, despite bringing about tissue
      necrosis. We conclude that photodynamic stress substantiates NO production and
      blood extravasation in situ, both processes on-going even in non-treated tumors,
      although at a lower intensity. 

PMID- 23973528
TI  - Ridaifen-SB8, a novel tamoxifen derivative, induces apoptosis via reactive oxygen
      species-dependent signaling pathway.
AB  - Tamoxifen is an anticancer agent widely used for treatment of estrogen receptor
      (ERalpha)-positive breast cancer. We previously developed a novel synthesis of
      tamoxifen and its derivatives, named Ridaifens (RIDs). Some of them, including
      RID-SB8, exhibited a stronger anticancer activity than tamoxifen in ERalpha
      positive MCF-7 cells while having lost the affinity for ERalpha, suggesting an
      ERalpha-independent anticancer mode of action. In this study, we investigated the
      underlying mechanism by which RID-SB8 exerts anticancer activity. As expected,
      anticancer activity of RID-SB8 was not influenced upon knockdown of ERalpha
      expression in MCF-7 cells. RID-SB8 exerted similar anticancer effects on thirteen
      ERalpha-negative cancer cell lines including human gliosarcoma SF539 cells. In
      SF539 cells, RID-SB8 triggered loss of mitochondrial membrane potential
      (DeltaPsi(m)) and progression of apoptosis accompanied by activation of caspases
      and translocation of apoptosis-inducing factor (AIF) to the nucleus. Furthermore,
      it induced reactive oxygen species (ROS), and a ROS scavenger, N-acetylcysteine
      (NAC), canceled loss of DeltaPsi(m) and progression of apoptosis triggered by RID
      SB8. Using fifteen human cancer cell lines, we demonstrated a significant
      correlation between RID-SB8 concentration required for ROS production and that
      required for cytotoxic effect across these cell lines, but such correlation was
      not observed for tamoxifen. Finally, the selective induction of ROS and cytotoxic
      effect on cancer cells by RID-SB8 were confirmed. From these results, we
      concluded that RID-SB8 exerts an anticancer effect via a mode of action distinct
      from tamoxifen, and that RID-SB8 could become a promising anticancer lead
      compound which selectively induces ROS formation and apoptosis in cancer cells.

PMID- 23973530
TI  - Smoking and fluidity of erythrocyte membranes: a high resolution scanning
      electron and atomic force microscopy investigation.
AB  - Smoking affects the general health of an individual, however, the red blood cells
      (RBCs) and their architecture are particularly vulnerable to inhaled toxins
      related to smoking. Smoking is one of the lifestyle diseases that are responsible
      for the most deaths worldwide and an individual who smokes is exposed to
      excessive amounts of oxidants and toxins which generate up to 10(18) free
      radicals in the human body. Recently, it was reported that smoking decreases RBC
      membrane fluidity. Here we confirm this and we show changes visible in the
      topography of RBC membranes, using scanning electron microscopy (SEM). RBC
      membranes show bubble formation of the phospholipid layer, as well as balloon
      like smooth areas; while their general discoid shapes are changed to form pointed
      extensions. We also investigate membrane roughness using atomic force microscopy
      (AFM) and these results confirm SEM results. Due to the vast capability of RBCs
      to be adaptable, their state of well-being is a major indication for the general
      health status of an individual. We conclude that these changes, using an old
      technique in a novel application, may provide new insights and new avenues for
      future improvements in clinical medicine pertaining to conditions like COPD. 

PMID- 23973531
TI  - Development of a high-throughput ultra performance liquid chromatography-mass
      spectrometry assay to profile 18 eicosanoids as exploratory biomarkers for
      atherosclerotic diseases.
AB  - Abundant evidence suggests a prominent role for eicosanoids and metabolites in
      the pathogenesis and prognosis of inflammatory diseases. A sensitive and high
      throughput SPE UPLC-MS/MS method was developed to quantitatively interrogate the
      levels of 18 eicosanoids in human and monkey plasma samples. A limit of
      quantitation of 0.25ng/mL was achieved for all 18 investigated compounds with
      linear ranges spanning four orders of magnitude. Bioanalytical performance of
      this assay was fully characterized including SPE extraction efficiency, matrix
      effect, autosampler stability, benchtop stability and freeze-thaw cycle
      variability. Endogenous levels of the eicosanoids and analogs within a set of
      monkey plasma samples challenged with lipopolysaccharide and human plasma samples
      were quantified by this ultra performance liquid chromatography-mass spectrometry
      (UPLC-MS/MS) assay. Quantitative eicosanoid profiles of the human samples were
      further analyzed by a non-supervised cluster analysis, which revealed a set of
      potential positive and negative lipid biomarkers to distinguish the following
      three groups: healthy individuals, hypertensive patients and severe
      atherosclerosis patients. The components of the negative biomarker cluster (8
      HETE, LTB4, 9-HODE and 13-HODE) are putative ligands of peroxisome proliferator
      activated receptors (PPARs), a family of master genes controlling the resolution
      of inflammatory signaling. 

PMID- 23973532
TI  - Evaluation of mixed-mode chromatographic resins for separating IgG from serum
      albumin containing feedstock.
AB  - Mixed-mode chromatography has been focused as a cost-effective new technique for
      antibody purification. In this study, four mixed-mode resins with N-benzyl-N
      methyl ethanol amine, 2-benzamido-4-mercaptobutanoic acide, 4-mercapto-ethyl
      pyridine and phenylpropylamine as the ligands were tested and the multi
      functional interactions between ligand and protein were discussed. Immunoglobulin
      G (IgG), bovine serum albumin (BSA) and the binary mixture of BSA and IgG were
      used as the model feedstock to compare the separation behaviors by pH gradient
      elution. The comparison analysis showed mixed-mode resin with N-benzyl-N-methyl
      ethanol amine as the ligand had the best ability to separate IgG and BSA. The
      results indicated that for four resins tested ionic interaction might play the
      dominant role in the separation of IgG and BSA while the hydrophobic interactions
      and hydrogen bonding have some subsidiary effects. The pH stepwise elution and
      sample loading were optimized to improve the IgG purification from serum albumin
      containing feedstock. High purity (92.3%) and high recovery (95.6%) of IgG were
      obtained. The results indicated that mixed-mode chromatography would be a
      potential option for antibody purification with the control of loading and
      elution conditions. 

PMID- 23973533
TI  - Development and validation of a new UPLC-PDA method to quantify linezolid in
      plasma and in dried plasma spots.
AB  - Linezolid is an oxazolidinone antibiotic used for the treatment of pneumonia and
      uncomplicated and complicated skin and soft tissues infections caused by Gram
      positive bacteria. It is also used as second line agent in multi-drug resistant
      tuberculosis. Therapeutic drug monitoring (TDM) of linezolid represents a valid
      tool in clinical practice to optimize therapy, especially in critically ill
      patients. Spreading of TDM is mainly limited by high costs shipment and lack of
      laboratories that offer a TDM service. To overcome these problems, the use of
      dried plasma spots or dried blood spots is increasing. The aim of this work was
      to develop and validate a new chromatographic method to analyze linezolid in
      plasma and in dried plasma spots and to evaluate the correlation between the two
      extraction methods. Linezolid extraction from plasma and from dried plasma spots
      was obtained using acetonitrile. Quinoxaline was used as internal standard.
      Analysis was performed by an ultra performance liquid chromatography (UPLC)
      system coupled with photo diode array (PDA) detector, at 254nm. Both analytical
      methods were linear (r(2)>0.999) over the calibration range of 30-0.117mg/L.
      Limit of quantification and limit of detection were 0.117mg/L and 0.058mg/L,
      respectively. Intra and inter-day precision (R.S.D.%) and accuracy (%) were <15%.
      Long term stability of linezolid in dried plasma spots showed absence of
      degradation at room temperature (20-25 degrees C) and at 4 degrees C, for at
      least one month. Linear regression analysis confirmed that the two methods of
      extraction have good correlation. Thus they are suited for TDM of linezolid and
      for pharmacokinetic studies. 

PMID- 23973534
TI  - Development of an HPLC fluorescence method for determination of boldine in
      plasma, bile and urine of rats and identification of its major metabolites by LC
      MS/MS.
AB  - Boldine belongs to the group of aporphine alkaloids isolated from Boldo tree. In
      contrast with numerous reports on the pharmacological effects of boldine, the
      data about its pharmacokinetics and biotransformation are scarce. No validated
      bioanalytical method of sufficient sensitivity has so far been described in the
      literature which could be used for quantification of boldine in various body
      fluids collected in pharmacokinetic studies. This work presents, for the first
      time, the assay for boldine in the plasma, bile and urine of rats. It includes
      liquid-liquid extraction/back-extraction of boldine, its chromatographic
      separation and sensitive fluorescence detection. Separation was carried out on a
      pentafluorophenyl core-shell column (Kinetex PFP, 150*3mm, 2.6MUm) in gradient
      elution mode with solvent system consisting of an acetonitrile-ammonium formate
      buffer (5mM, pH=3.8). Fluorimetric detection (lambdaEX=320nm, lambdaEM=370nm) was
      used for quantitative work. Validation according to the EMEA guideline proved the
      assay LLOQ (0.1MUmolL(-1)), linearity over a broad range of 0.1-50MUmolL(-1),
      precision (intra- and inter-day CVs less than 4.5% and 6.1%, respectively) and
      accuracy (relative errors between -5.8% and 4.8%). In a pilot pharmacokinetic
      experiment, the concentration-time profiles were described for boldine (single
      i.v. bolus 50mgkg(-1)) in plasma and bile and cumulative excretion in urine was
      investigated. The major metabolites identified by means of LC-MS(n) were boldine
      O-glucuronide, boldine-O-sulphate and disulphate, boldine-O-glucuronide-O
      sulphate and N-demethyl-boldine-O-sulphate. 

PMID- 23973535
TI  - Fungal-bacterial consortia increase diuron degradation in water-unsaturated
      systems.
AB  - Bioremediation of pesticide-polluted soil may be more efficient using mixed
      fungal-bacterial cultures rather than the individual strains alone. This may be
      due to cooperative catabolism, where the first organism transforms the pollutant
      to products which are then used by the second organism. In addition, fungal
      hyphae may function as transport vectors for bacteria, thereby facilitating a
      more effective spreading of degrader organisms in the soil. A more rapid
      mineralization of the phenylurea herbicide diuron was found in sand with added
      microbial consortia consisting of both degrading bacteria and fungi. Facilitated
      transport of bacteria by fungal hyphae was demonstrated using a system where
      herbicide-spiked sand was separated from the consortium by a layer of sterile
      glass beads. Several fungal-bacterial consortia were investigated by combining
      different diuron-degrading bacteria (Sphingomonas sp. SRS2, Variovorax sp. SRS16,
      and Arthrobacter globiformis D47) and fungi (Mortierella sp. LEJ702 and LEJ703).
      The fastest mineralization of (14)C-labeled diuron was seen in the consortium
      consisting of Mortierella LEJ702, Variovorax SRS16, and A. globiformis D47, as
      measured by evolved (14)CO2. In addition, the production of diuron metabolites by
      this consortium was minimal. Analyses of 16S rDNA suggested that bacteria were
      transported more efficiently by LEJ702 than by LEJ703. Finally, it was determined
      that the fungal growth differed for LEJ702 and LEJ703 in the three-member
      consortia. This study demonstrates new possibilities for applying efficient
      fungal-bacterial consortia for bioremediation of polluted soil. 

PMID- 23973536
TI  - Association between thyroid function and selected organochlorine pesticides: data
      from NHANES 2001-2002.
AB  - Exposure to organochlorine pesticides (OCP) has been shown to be associated with
      adverse thyroid function. The impact of exposure to selected OCPs on total serum
      thyroxine (TT4) and thyroid stimulating hormone (TSH) was evaluated by analyzing
      data from the 2001-2002 National Health and Nutrition Examination Survey.
      Oxychlordane, p,p'-DDE, trans-nonachlor, and heptachlor epoxide were selected for
      analysis. Regression models with logs of TSH and TT4 as dependent variables and
      OCP exposure, race/ethnicity, iodine and smoking status, total lipids and others
      as independent variables were fitted. TSH levels increased (p < 0.05) with
      increase in trans-nonachlor exposure for 20-39 year old iodine deficient males.
      TSH levels were higher when oxychlordane exposure was low than when the exposure
      was medium or high for 20-39 year old iodine deficient females (p < 0.05). For
      iodine deficient females, TT4 levels were lower when p,p'-DDE exposure was low
      than when it was medium (p < 0.05). For non-Hispanic blacks (NHB), TT4 levels
      decreased with increase in exposure to heptachlor epoxide (p < 0.05). For iodine
      replete males, TSH levels increased with increase in trans-nonachlor exposure (p
      < 0.05). For iodine replete females, (i) Mexican Americans (MA) had higher TSH
      levels when the exposure to oxychlordane was medium than when the exposure was
      low; (ii) for 60+years old, there was a positive association between TSH and
      heptachlor epoxide levels; and (iii) TT4 levels had an inverse association with
      trans-nonachlor and oxychlordane. In general though not always, (i) TSH and TT4
      levels were lowest for the 20-39 years old and highest for the 60+years old (p <
      = 0.05), (ii) TSH and TT4 levels for iodine deficient males and females were
      lowest for NHB, highest for MA, and in-between for non-Hispanic white, and (iii)
      non-smokers had higher TSH and TT4 levels than smokers and in general,
      statistically significantly so.

PMID- 23973537
TI  - qPCR standard operating procedure for measuring microorganisms in dust from
      dwellings in large cohort studies.
AB  - The aim of the present study was to assess performance, feasibility and relevance
      of a Standard Operational Procedure (SOP) for large-scale use in the microbial
      analysis of children's indoor environments. We analyzed dust settled on
      Electrostatic Dust Fall Collectors (EDCs) by using qPCR which targeted 6 molds, 3
      bacteria and 1 mite, chosen for their involvement in allergic or inflammatory
      processes. Six types of commercialized electrostatic wipes were tested for their
      releasing capacity of fungal DNA from fungal spores captured by the wipes.
      Specificity, repeatability and detection limits of the qPCR procedure were tested
      using calibrated microbial suspensions. The feasibility and relevance of this
      sampling and analysis method were assessed in a 75-home pilot study. Our result
      showed that one specific make of wipe was more effective than the others in
      releasing fungal DNA. qPCR procedure showed good repeatability. The
      quantification limit was about 5 fg DNA/MUL for all species except Penicillium
      chrysogenum (0.5 fg DNA/MUL) and Dermatophagoides pteronyssinus (10 fg DNA/MUL).
      No cross-reactivity was observed. DNA concentrations in the 53/75 homes
      participating in the pilot study were between 0 and 24 625, 0 and 69 738
      equivalent cells per cm(2) for the fungi and bacteria, and between 0 and 1
      equivalent mites per cm(2) for D. pteronyssinus. Using the SOP described, we were
      able to classify the 53 dwellings from the least to the most contaminated
      according to the quantity of DNA measured for each species. Our SOP measured
      fungi, bacteria and mites using a cost-efficient, discreet and well-accepted
      sampling method with just one qPCR tool. The whole procedure can be used for
      microbial analysis in large cohort studies such as the ELFE study ("Etude
      Longitudinale Francaise depuis l'Enfance") and could help improve our
      understanding of the interactions between the environment, allergic diseases and
      child development.

PMID- 23973538
TI  - Size-selective assessment of agricultural workers' personal exposure to airborne
      fungi and fungal fragments.
AB  - Fungi are ubiquitous agents that cause human respiratory diseases. Very few
      studies have size-selectively assessed farmers' exposure to fungi and fungal
      fragments in agricultural settings. In this study, a two-stage bio-aerosol
      cyclone personal sampler was employed to collect airborne fungi and fungal
      fragments size-selectively at corn, swine, poultry, and mushroom farms. The
      collected air samples were analyzed for culturable fungi, fungal spores, viable
      fungi and (1 -> 3)-beta-D-glucan. The results show that the median concentrations
      ranged from 3.2 * 10(5) to 1.3 * 10(8)spores/m(3) for total fungal spores, from
      1.3 * 10(5) to 5.1 * 10(7)spores/m(3) for total viable fungi, from 1.9 * 10(3) to
      1.5 * 10(7)CFU/m(3) for total culturable fungi, and from 4.3 * 10(3) to 2.4 *
      10(6)pg/m(3) for total (1 -> 3)-beta-D-glucan. The aerodynamic sizes of most of
      the collected fungal contaminants were larger than 1.8 MUm. Total (1 -> 3)-beta-D
      glucan significantly correlated with total fungal spores (r = 0.65, p < 0.001),
      total viable fungi (r = 0.68, p < 0.001) and total culturable fungi (r = 0.72, p
      < 0.001). Total (1 -> 3)-beta-D-glucan significantly correlated with
      Aspergillus/Penicillium, Alternaria, and Cladosporium. Alternaria and Botrytis
      were also found to highly correlate with (1 -> 3)-beta-D-glucan at the size <1
      MUm, which was less than the expected spore sizes (the mean measured aerodynamic
      sizes were 18.5 MUm for Alternaria and 6.1 MUm for Botrytis); therefore,
      Alternaria and Botrytis might release small fragments that could enter the deep
      lung and cause respiratory diseases.

PMID- 23973539
TI  - Seasonal surveillance of airborne PCDD/Fs, PCBs and PCNs using passive samplers
      to assess human health risks.
AB  - This study aimed at determining the air concentrations of polychlorinated dibenzo
      p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) and
      polychlorinated naphthalenes (PCNs) near a municipal solid waste incinerator
      (MSWI) in Tarragona (Catalonia, Spain) by means of passive air sampling. Seasonal
      trends in airborne levels were also assessed by comparing the results of 6-month
      surveys conducted between spring of 2010 and autumn of 2011. These data were used
      to estimate exposure for the population living nearby and to evaluate the non
      carcinogenic and carcinogenic risks associated to inhalation of those persistent
      organic pollutants (POPs). No seasonal differences were noted in POP
      concentrations among the sampling campaigns. The highest levels of PCDD/Fs were
      found in the 3rd campaign, while significantly lower levels of PCNs were found in
      the 4th survey. The concentrations of PCDD/F and PCB congeners, as well as those
      of PCN homologues, did not change significantly with time, which indicates that
      the MSWI does not have an important influence on the surrounding environment. The
      levels of POPs near the facility are at the lower part of the range, when
      compared with data from the scientific literature. Consequently, the current
      levels of POPs in ambient air around the MSWI are associated to a low human
      exposure to PCDD/Fs, PCBs and PCNs, which means a lack of additional health risks
      for the local population. In addition, passive samplers have been confirmed to be
      a good tool for local environmental monitoring, as well as a good method to study
      seasonal trends in POP concentrations in air. 

PMID- 23973540
TI  - Quantifying the hydrological impact of simulated changes in land use on peak
      discharge in a small catchment.
AB  - A physically-based, distributed hydrological model (MIKE SHE) was used to
      quantify overland runoff in response to four extreme rain events and four types
      of simulated land use measure in a catchment in Norway. The current land use in
      the catchment comprises arable lands, forest, urban areas and a stream that
      passes under a motorway at the catchment outlet. This model simulation study
      demonstrates how the composition and configuration of land use measures affect
      discharge at the catchment outlet differently in response to storms of different
      sizes. For example, clear-cutting on 30% of the catchment area produced a 60%
      increase in peak discharge and a 10% increase in total runoff resulting from a 50
      year storm event in summer, but the effects on peak discharge were less
      pronounced during smaller storms. Reforestation of 60% of the catchment area was
      the most effective measure in reducing peak flows for smaller (2-, 5- and 10
      year) storms. Introducing grassed waterways reduced water velocity in the stream
      and resulted in a 28% reduction in peak flow at the catchment outlet for the 50
      year storm event. Overall, the results indicate that the specific effect of land
      use measures on catchment discharge depends on their spatial distribution and on
      the size and timing of storm events. 

PMID- 23973541
TI  - Profile and behavior of antiviral drugs in aquatic environments of the Pearl
      River Delta, China.
AB  - Occurrence and behavior of six antiviral pharmaceuticals (acyclovir, ganciclovir,
      oseltamivir, ribavirin, stavudine and zidovudine) and one active metabolite
      oseltamivir carboxylate were investigated in wastewater, landfill leachate, river
      water, reservoir and well water in the vicinity of municipal landfills in the
      Pearl River Delta, China. Acyclovir was the only antiviral detected in the
      wastewater at 177-406 (mean=238) and 114-205 (mean=154) ng L(-1) in the influent
      and final effluent, respectively. Aerobic biodegradation appeared to be the main
      process for the elimination of acyclovir in the wastewater. Acyclovir was also
      the only antiviral quantitatively detected in the Pearl River and its
      tributaries, with a maximum concentration up to 113 ng L(-1). Treated wastewater
      was a major source of acyclovir in the rivers. The highest concentration of
      acyclovir was observed in winter in the river water and the dilution effect by
      precipitation was suggested to be the dominant factor impacting the seasonal
      pattern of acyclovir in the rivers. No antivirals were quantitatively detected in
      the well water whereas acyclovir was frequently detected in the reservoirs at a
      maximal concentration of 33.6 ng L(-1) in the vicinity of the municipal
      landfills. However, source identification and fate of acyclovir in the reservoirs
      pend on further research.

PMID- 23973542
TI  - Combined use of WEPS and Models-3/CMAQ for simulating wind erosion source
      emission and its environmental impact.
AB  - The wind erosion source is the greatest contributor of PM10 in Tianjin, China. It
      is difficult to establish a PM10 emission inventory for the wind erosion source
      because of the complicated conditions affecting PM10 emissions from wind erosion.
      In this study, a novel method is developed to establish a PM10 emission inventory
      for the wind erosion source by using the Wind Erosion Prediction System (WEPS)
      model with 1 * 1 km spatial resolution. In 2011, the average annual emission of
      PM10 in Tianjin was 0.373 tons km(-2) (1.113 tons km(-2) in the heating period,
      0.237 tons km(-2) in the sand period, and 0.013 tons km(-2) in the non-heating
      period), and the total PM10 emission was 904,871.6 tons (221,080.7 tons in the
      heating period, 52,977.8 tons in the sand period, and 1953.2 tons in the non
      heating period). After establishing the PM10 emission inventory for the wind
      erosion source in this manner, the data were input into Model-3/SMOKE. The
      contribution of the PM10 concentration from the wind erosion source was estimated
      using the Community Multi-scale Air Quality (Model-3/CMAQ) model and was compared
      with the monitoring value and the source apportionment results using the chemical
      mass balance (CMB) method. For this comparison, over the entire year, the R(2)
      was 0.711. More specifically, R(2) was 0.664, 0.733, and 0.679 in the heating,
      non-heating, and sand periods, respectively. Thus, we have obtained a reliable
      method for estimating the source of PM10 from wind erosion.

PMID- 23973544
TI  - Concentration and characteristics of dissolved carbon in the Sanjiang Plain
      influenced by long-term land reclamation from marsh.
AB  - Since the 1960s, the marshes in the Sanjiang Plain, Northeast China, which are an
      important reservoir for dissolved carbon, have undergone long-term reclamation to
      farmland, resulting in elevated marsh loss and degradation on a large scale. This
      study compared the concentrations of dissolved carbon, as well as the chemical
      characteristics of dissolved organic carbon (DOC), in natural marshes, a degraded
      marsh, and drainage ditches sampled during the growing seasons between 2008 and
      2010 to clarify the temporal-spatial variability of the dissolved carbon in the
      fluvial system influenced by the long-term reclamation. The results show that the
      average concentrations of total dissolved carbon (TDC) and DOC are considerably
      greater in the natural marshes than in the degraded marsh and drainage ditches.
      The average DOC concentration for the natural marshes, approximately 35.53 +/-
      5.15 mg L(-1), is approximately 2.39 times that in the degraded marsh (14.84 +/-
      4.21 mg L(-1)) and 2.77 times the average value in the ditches (12.84 +/- 4.49 mg
      L(-1)). The dissolved inorganic carbon (DIC) exhibits increased trends in the
      drainage ditches compared with the natural marshes, whereas the hydrophobic
      fraction of DOC is present at lower concentrations in the degraded marsh and
      ditches. Fluorescence indices also indicate that the DOC in the degraded marsh
      and ditches has a simpler humification structure. In total, the long-term
      reclamation has led to great variability in the DOC concentration and chemical
      characteristics in the fluvial system. Changes in the DOC production potential
      and hydrological regimes due to sustained reclamation are deemed the predominant
      causes of this effect. The continuously decreased DOC concentration and high
      variability of DOC in the surface fluvial systems are inevitable if reclamation
      continues in the Sanjiang Plain. More importantly, the presence of tyrosine and
      tryptophan-like substances in the ditches indicates that there has been extensive
      agricultural organic pollution in the fluvial systems. This pollution could lead
      to more unexpected impacts on the downriver aquatic system. To avoid a
      destructive ecological crisis in the future, adjustment of the reclamation policy
      and agricultural management measures in the Sanjiang Plain is urgently needed.

PMID- 23973545
TI  - Predicting the toxicity of metal mixtures.
AB  - The toxicity of single and multiple metal (Cd, Cu, Pb, and Zn) solutions to trout
      is predicted using an approach that combines calculations of: (1) solution
      speciation; (2) competition and accumulation of cations (H, Ca, Mg, Na, Cd, Cu,
      Pb, and Zn) on low abundance, high affinity and high abundance, low affinity
      biotic ligand sites; (3) a toxicity function that accounts for accumulation and
      potency of individual toxicants; and (4) biological response. The approach is
      evaluated by examining water composition from single metal toxicity tests of
      trout at 50% mortality, results of theoretical calculations of metal accumulation
      on fish gills and associated mortality for single, binary, ternary, and
      quaternary metal solutions, and predictions for a field site impacted by acid
      rock drainage. These evaluations indicate that toxicity of metal mixtures depends
      on the relative affinity and potency of toxicants for a given aquatic organism,
      suites of metals in the mixture, dissolved metal concentrations and ratios, and
      background solution composition (temperature, pH, and concentrations of major
      ions and dissolved organic carbon). A composite function that incorporates
      solution composition, affinity and competition of cations for two types of biotic
      ligand sites, and potencies of hydrogen and individual metals is proposed as a
      tool to evaluate potential toxicity of environmental solutions to trout. 

PMID- 23973546
TI  - Phototoxicity of TiO2 nanoparticles to a freshwater benthic amphipod: are benthic
      systems at risk?
AB  - This study investigated phototoxicity of TiO2 nanoparticles (nano-TiO2) to a
      freshwater benthic amphipod (Hyalella azteca) using 48-h and 96-h bioassays.
      Thorough monitoring of particle interactions with exposure media (Lake Superior
      water, LSW) and the surface of organisms was performed using dynamic light
      scattering, UV/Vis spectroscopy, and Scanning Electron Microscopy. Large
      agglomeration and sedimentation (>77%) in LSW was observed after 0.5h. A
      simulated solar radiation (SSR)-favored surface attachment of nanoparticles was
      observed, indicating enhanced phototoxicity with the increased attachment. A 96-h
      median lethal concentration (LC50) of 29.9 mg/L in H. azteca was calculated, with
      a daily 4-h UV exposure of 2.2 W/m(2). Phototoxicity of nano-TiO2 under SSR had a
      21-fold increase as compared to that under ambient laboratory light. This
      phototoxicity was also dependent on UV dose, with calculated LC50s around 22.9
      (95% CI, 20.5-23.3)Wh/m(2) when exposed to 20 mg/L nano-TiO2. Also, H. azteca
      exhibited negative phototaxis in the presence of shelters, indicating that other
      factors might play a role in environmental systems. Finally, the environmental
      implications of nano-TiO2 to benthic organisms were illustrated, emphasizing the
      importance of various environmental factors in the ultimate phototoxicity. This
      increased phototoxicity and its complex interactions with various environmental
      factors suggest further investigations are needed for future risk assessment of
      photoactive nanomaterials to benthic organisms.

PMID- 23973547
TI  - Emission inventories and modeling requirements for the development of air quality
      plans. Application to Madrid (Spain).
AB  - Modeling is an essential tool for the development of atmospheric emission
      abatement measures and air quality plans. Most often these plans are related to
      urban environments with high emission density and population exposure. However,
      air quality modeling in urban areas is a rather challenging task. As
      environmental standards become more stringent (e.g. European Directive
      2008/50/EC), more reliable and sophisticated modeling tools are needed to
      simulate measures and plans that may effectively tackle air quality exceedances,
      common in large urban areas across Europe, particularly for NO2. This also
      implies that emission inventories must satisfy a number of conditions such as
      consistency across the spatial scales involved in the analysis, consistency with
      the emission inventories used for regulatory purposes and versatility to match
      the requirements of different air quality and emission projection models. This
      study reports the modeling activities carried out in Madrid (Spain) highlighting
      the atmospheric emission inventory development and preparation as an illustrative
      example of the combination of models and data needed to develop a consistent air
      quality plan at urban level. These included a series of source apportionment
      studies to define contributions from the international, national, regional and
      local sources in order to understand to what extent local authorities can enforce
      meaningful abatement measures. Moreover, source apportionment studies were
      conducted in order to define contributions from different sectors and to
      understand the maximum feasible air quality improvement that can be achieved by
      reducing emissions from those sectors, thus targeting emission reduction policies
      to the most relevant activities. Finally, an emission scenario reflecting the
      effect of such policies was developed and the associated air quality was modeled.

PMID- 23973543
TI  - Prenatal exposure to hexachlorobenzene (HCB) and reproductive effects in a
      multicentre birth cohort in Spain.
AB  - OBJECTIVE: To investigate the possible association between birth size or
      gestational length and maternal serum concentrations of hexachlorobenzene (HCB)
      in a population exposed to background levels. METHODS: A total of 1568 mother
      child pairs recruited in three Spanish areas (INMA Project) from 2004 to 2008
      participated in the study. Multivariate analysis was performed between birth
      weight and length, weeks of gestation, preterm birth or small for gestational age
      and HCB concentrations in maternal serum. RESULTS: The median concentration of
      HCB was 45.45 ng/g lipids. No association was found between HCB exposure levels
      and birth weight (beta: -50.42 [-109.88; 9.04]), birth length (beta: -0.07 [
      0.32; 0.18]), gestation age (HR: 1.07 [0.94; 1.22]), small for gestational age
      (OR: 0.95 [0.56; 1.61]) and preterm birth (OR: 0.60 [0.29; 1.28]). Results remain
      similar after adjustment for other organochlorines. CONCLUSION: Our findings
      support the idea that exposure to low levels of HCB does not affect the
      intrauterine growth nor the duration of gestation.

PMID- 23973548
TI  - Banded applications are highly effective in minimising herbicide migration from
      furrow-irrigated sugar cane.
AB  - Runoff from farm fields is a common source of herbicide residues in surface
      waters in many agricultural industries around the world. In Queensland,
      Australia, the runoff of PSII inhibitor herbicides (in particular diuron and
      atrazine) is a major concern due to their potential impact on the Great Barrier
      Reef. This study compared the conventional practice of broadcast application of
      herbicides in sugarcane production across the whole field with the banded
      application of particular herbicides onto raised beds only using a shielded
      sprayer. This study found that the application of two moderately soluble
      herbicides, diuron and atrazine, to only the raised beds decreased the average
      total load of both herbicides moving off-site by >90% compared with the
      conventional treatment. This was despite the area being covered with the
      herbicides by the banded application being only 60% less than with the
      conventional treatment. The average total amount of atrazine in drainage water
      was 7.5% of the active ingredient applied in the conventional treatment compared
      with 1.8% of the active ingredient applied in the banded application treatment.
      Similarly, the average total amount of diuron in drainage water was 4.6% of that
      applied in the conventional treatment compared with 0.9% of that applied in the
      banded application treatment. This study demonstrates that the application of
      diuron and atrazine to raised beds only is a highly effective way of minimising
      migration of these herbicides in drainage water from furrow irrigated sugarcane. 

PMID- 23973549
TI  - Developing a flow control strategy to reduce nutrient load in a reclaimed multi
      reservoir system using a 2D hydrodynamic and water quality model.
AB  - Blocking the natural bi-directional flow in an estuarine system using an
      artificial dyke has commonly caused serious water quality problems. In the
      southwestern part of South Korea, a parallel triple-reservoir system was
      constructed by blocking the mouth of three different rivers (Yeongsan, Okcheon,
      and Kumja), which were then interconnected using two open channels. This system
      has experienced a deterioration in water quality due to pollutants accumulated
      from the upper watershed, and has continually discharged pollutant loads to the
      outer ocean. Therefore, the objective of this study is to establish an effective
      dam operation plan for reducing nutrient loads released from the integrated
      reservoir. In this study, the CE-QUAL-W2 model, which is a 2-dimentional
      hydrodynamic and water quality model, was applied to predict the pollutant load
      released from each reservoir in response to different flow scenarios for the
      interconnecting channel. The model was calibrated using two novel methods: a
      sensitivity analysis to determine meaningful model parameters, and a pattern
      search to optimize the parameters. From the scenario analysis using flow control,
      it was determined that the total nitrogen (TN) and total phosphorus (TP) loadings
      could be reduced by 27.2% and 6.6%, respectively, under the optimal channel flow
      scenario by regulating the chlorophyll-a concentration in the reservoir. The
      results confirm that effective dam operation could contribute to a decrease in
      pollutant loads in the receiving seawater body. As such, this study suggests
      operational strategies for a multi-reservoir system that can be used to reduce
      the nutrient load being discharged from reservoirs. 

PMID- 23973550
TI  - Changes in the planktonic microbial community during residence in a surface flow
      constructed wetland used for tertiary wastewater treatment.
AB  - Suspended particles are a major constituent of municipal wastewater and generally
      contain high levels of bacteria, including human pathogens. Discharge of these
      particles of anthropogenic nature can have profound effects on receiving aquatic
      ecosystems and mitigation of these effects requires additional polishing of
      treated municipal wastewater. Previously it was shown that surface flow
      constructed wetlands are effective in improving water quality by reducing the
      numbers of fecal indicator organisms. However, fecal indicator organisms
      represent only a minor fraction of the total planktonic bacterial community and
      knowledge on the effects of these constructed wetlands on the composition and
      functioning of the entire planktonic bacterial community is limited. The aim of
      this descriptive study was therefore to identify changes in the planktonic
      bacterial community during residence of secondary treated municipal wastewater in
      a full-scale surface flow constructed wetland. To this purpose water samples were
      taken in which the bacterial community composition and functioning were analyzed
      using FISH, DGGE and BIOLOG. Surprisingly, the bacterial abundance at the inflow
      of the constructed wetland was relatively low compared with more natural surface
      waters. However, the inflowing bacterial community showed high metabolic activity
      and functional diversity. During residence in the surface flow constructed
      wetland the bacterial abundance doubled, but decreased in metabolic activity and
      functional diversity. Shifts in the community composition indicate that these
      changes are related to turn-over of the bacterial community. The planktonic
      bacterial community in the effluent of the constructed wetland closely resembled
      natural bacterial communities in urban and agricultural ditches. Based on these
      observations we conclude that constructed wetlands are capable to mitigate
      possible impacts of the particle load in treated wastewaters by transforming the
      anthropological bacterial community to a bacterial community resembling more
      "natural" surface waters. 

PMID- 23973551
TI  - Sanitation ability of anaerobic digestion performed at different temperature on
      sewage sludge.
AB  - A small amount of ammonia is used in full-scale plants to partially sanitize
      sewage sludge, thereby allowing successive biological processes to enable the
      high biological stability of the organic matter. Nevertheless, ammonia and
      methane are both produced during the anaerobic digestion (AD) of sludge. This
      paper describes the evaluation of a lab-scale study on the ability of anaerobic
      process to sanitize sewage sludge and produce biogas, thus avoiding the addition
      of ammonia to sanitize sludge. According to both previous work and a state of the
      art full-scale plant, ammonia was added to a mixture of sewage sludge at a rate
      so that the pH values after stirring were 8.5, 9 and 9.5. This procedure
      determined an ammonia addition lower than that generally indicated in the
      literature. The same sludge was also subjected to an AD process for 60 days under
      psychrophilic, mesophilic and thermophilic conditions. The levels of fecal
      coliform, Salmonella spp. helmints ova, pH, total N, ammonia fractions and biogas
      production were measured at different times during each process. The results
      obtained suggested that sludge sanitation can be achieved using an AD process;
      however, the addition of a small amount of ammonia was not effective in sludge
      sanitation because the buffer ability of the sludge reduced the pH and thus
      caused ammonia toxicity. Mesophilic and thermophilic AD sanitized better than
      psychrophilic AD did, but the total free ammonia concentration under the
      thermophilic condition inhibited biogas production. The mesophilic condition,
      however, allowed for both sludge sanitation and significant biogas production.

PMID- 23973552
TI  - The role of metallothionein and selenium in metal detoxification in the liver of
      deep-sea fish from the NW Mediterranean Sea.
AB  - Seven deep-sea fish species were sampled in the Blanes Canyon area (NW
      Mediterranean) at a depth of 1200 m during winter. The concentrations of nine
      metals were determined in the liver of these species by ICP-MS. Furthermore, the
      metal detoxification potential was determined for each species by analysing the
      hepatic metallothionein (MT) content, relations between metals and the molar
      ratio between MT and/or selected metals. The potential effect of metal content on
      their physiology was assessed using general stress markers such as the enzyme
      activities of acetylcholinesterase (AChE) and lactate dehydrogenase (LDH) in
      muscle. Levels of metals in the seven Mediterranean deep-sea fish species studied
      were intermediate to equivalent species of fish either from Atlantic waters or
      hydrothermal vents. The metal detoxification potential varied among species
      depending on MT, selenium (Se) or zinc (Zn) as reliable mechanisms to handle
      potential metal toxicity. The role of Se was especially relevant when the liver
      content of mercury (Hg) was higher. AChE and LDH activities did seem to be
      affected by metal loads and thus the activities reported would correspond to
      baseline activities of the selected species.

PMID- 23973553
TI  - Effect of soil organic amendments on the behavior of bentazone and tricyclazole.
AB  - The effect of soil amendment with different organic residues from olive oil
      production on the sorption and leaching of two pesticides used in rice crops
      (bentazone and tricyclazole) was compared in order to understand their behavior
      and to improve soil properties by recycling an abundant agricultural residue in
      Andalucia (S. Spain). A residue from olive oil production (AJ), the organic
      compost derived from this organic waste (CA) and a biochar (BA) made from CA were
      used. A soil devoted to rice cultivation, IFAPA (I), was amended at 2% (w/w) of
      each amendment individually (I+AJ, I+CA and I+BA). In order to evaluate the
      effect of dissolved organic matter (DOM) from these amendments on bentazone and
      tricyclazole behavior, the DOM from the amendments was extracted, quantified and
      characterized by fluorescence spectroscopy and FT-IR. The affinity of DOM for
      soil surfaces was evaluated with (I) soil and two other soils of different
      physicochemical properties, ARCO (A) and GUAD (G). These studies revealed
      differences in DOM quantity, quality and affinity for the used soils among
      amendments which can explain the different sorption behavior observed for
      tricyclazole in the amended soils. Leaching assays under saturated/unsaturated
      conditions revealed a slight delay of bentazone in I+CA and I+BA soils when
      compared to I+AJ, that can be related to the higher DOM content and much lower
      specific surface area of AJ. In contrast, tricyclazole was not detected in any of
      the leachates during the leaching assay. Extraction of tricyclazole residues from
      soil columns showed that the fungicide did not move below 5cm in the higher
      sorptive systems (I+CA, I+BA). The sorption of DOM from amendments on soil during
      the transport process can decrease the mobility of the fungicide by changing the
      physicochemical properties of the soil surface whose behavior may be dominated by
      the adsorbed DOM. 

PMID- 23973554
TI  - EphrinB-EphB receptor signaling contributes to bone cancer pain via Toll-like
      receptor and proinflammatory cytokines in rat spinal cord.
AB  - Treating bone cancer pain poses a major clinical challenge, and the mechanisms
      underlying bone cancer pain remain elusive. EphrinB-EphB receptor signaling may
      contribute to bone cancer pain through N-methyl-d-aspartate receptor neuronal
      mechanisms. Here, we report that ephrinB-EphB signaling may also act through a
      Toll-like receptor 4 (TLR4)-glial cell mechanism in the spinal cord. Bone cancer
      pain was induced by tibia bone cavity tumor cell implantation (TCI) in rats. TCI
      increased the expression of TLR4 and the EphB1 receptor, the activation of
      astrocytes and microglial cells, and increased levels of interleukin-1beta (IL
      1beta) and tumor necrosis factor-alpha (TNF-alpha). The increased expression of
      TLR4 and EphB1 were colocalized with each other in astrocytes and microglial
      cells. Spinal knockdown of TLR4 suppressed TCI-induced behavioral signs of bone
      cancer pain. The TCI-induced activation of astrocytes and microglial cells, as
      well as the increased levels of IL-1beta and TNF-alpha, were inhibited by
      intrathecal administration of TLR4-targeting siRNA2 and the EphB receptor
      antagonist EphB2-Fc, respectively. The administration of EphB2-Fc suppressed the
      TCI-induced increase of TLR4 expression but siRNA2 failed to affect TCI-induced
      EphB1 expression. Intrathecal administration of an exogenous EphB1 receptor
      activator, ephrinB2-Fc, increased the expression of TLR4 and the levels of IL
      1beta and TNF-alpha, activated astrocytes and microglial cells, and induced
      thermal hypersensitivity. These ephrinB2-Fc-induced alterations were suppressed
      by spinal knockdown of TLR4. This study suggests that TLR4 may be a potential
      target for preventing or reversing bone cancer pain and other similar painful
      processes mediated by ephrinB-EphB receptor signaling. 

PMID- 23973555
TI  - Use of a web 2.0 portal to improve education and communication in young patients
      with families: randomized controlled trial.
AB  - BACKGROUND: Diabetes requires extensive self-care and comprehensive knowledge,
      making patient education central to diabetes self-management. Web 2.0 systems
      have great potential to enhance health information and open new ways for patients
      and practitioners to communicate. OBJECTIVE: To develop a Web portal designed to
      facilitate self-management, including diabetes-related information and social
      networking functions, and to study its use and effects in pediatric patients with
      diabetes. METHODS: A Web 2.0 portal was developed in collaboration with patients,
      parents, and practitioners. It offered communication with local practitioners,
      interaction with peers, and access to relevant information and services. Children
      and adolescents with diabetes in a geographic population of two pediatric clinics
      in Sweden were randomized to a group receiving passwords for access to the portal
      or a control group with no access (n=230) for 1 year. All subjects had access
      during a second study year. Users' activity was logged by site and page visits.
      Health-related quality of life (HRQOL), empowerment (DES), and quality of
      information (QPP) questionnaires were given at baseline and after 1 and 2 study
      years. Clinical data came from the Swedish pediatric diabetes quality registry
      SWEDIABKIDS. RESULTS: There was a continuous flow of site visits, decreasing in
      summer and Christmas periods. In 119/233 families (51%), someone visited the
      portal the first study year and 169/484 (35%) the second study year. The outcome
      variables did not differ between intervention and control group. No adverse
      treatment or self-care effects were identified. A higher proportion of mothers
      compared to fathers visited once or more the first year (P<.001) and the second
      year (P<.001). The patients who had someone in the family visiting the portal 5
      times or more, had shorter diabetes duration (P=.006), were younger (P=.008), had
      lower HbA1c after 1 year of access (P=.010), and were more often girls (P<.001).
      Peer interaction seems to be a valued aspect. CONCLUSIONS: The Web 2.0 portal may
      be useful as a complement to traditional care for this target group. Widespread
      use of a portal would need integration in routine care and promotion by diabetes
      team members. TRIAL REGISTRATION: International Standard Randomized Controlled
      Trial Number (ISRCTN):92107365; http://www.controlled-trials.com/ISRCTN92107365/
      (Archived by WebCite at http://webcitation.org/6IkiIvtSb).

PMID- 23973556
TI  - Neuromodulation and developmental contextual influences on neural and cognitive
      plasticity across the lifespan.
AB  - Behavioral, cognitive, and motivational development entails co-constructive
      interactions between the environmental and social influences from the
      developmental context, on the one hand, and the individual's neurobiological
      inheritance, on the other hand. Key brain networks underlying cognition, emotion,
      and motivation are innervated by major transmitter systems (e.g., the
      catecholamines and acetylcholine). Thus, the maturation and senescence of
      neurotransmitter systems have direct implications for lifespan development. In
      addition to reviewing evidence on life age differences in dopaminergic modulation
      and cognitive development, this brief review selectively highlights recent
      findings on how important influences from the developmental context, such as
      reward-mediated motivational processes, transgenerational stress transmission,
      psychosocial stress, and cognitive interventions, may, in part, exert their
      effects on brain and behavioral development through their effects on
      neuromodulatory mechanisms. 

PMID- 23973557
TI  - Proton pump inhibitor use and fracture risk - effect modification by histamine H1
      receptor blockade. Observational case-control study using National Prescription
      Data.
AB  - It remains unknown why proton pump inhibitor (PPI) use may be associated with
      risk of osteoporotic fractures; evidence of direct effects on calcium absorption
      or on the osteoclast in humans is weak or absent. However, the ensuing increased
      gastrin levels may cause histamine production through hypertrophy of gastric
      enterochromaffin like cells, which could lead to bone loss. We speculated that H1
      receptor antagonists (H1RA) used for allergies would then reduce the effect of
      PPI on bone. We therefore conducted a register-based case-control study
      comprising 124,655 patients with hospital treated fractures, who were matched 3:1
      with non fracture control subjects of the same age and gender. Use of
      prescription medications was retrieved from the National Prescription Database
      and data was analyzed using conditional logistic regression analysis. We observed
      a significant interaction between PPI and H1RA use on fracture risk in general
      (adjusted OR 0.92, 95% CI 0.87-0.98) though not on hip fracture risk (adjusted OR
      0.99, 95% CI 0.85-1.16). There was a significant modification of the interaction
      by age (p<0.05 for both fracture categories). As previously shown, fracture risk
      was higher in PPI users both for fractures in general and for hip fractures.
      Irrespective of PPI use, H1RA users had lower risk of hip fractures than non
      users (adjusted OR 0.86, 95% CI 0.79-0.93). This short report suggests that the
      effects of PPI on bone could be driven by in part by increased histamine release
      as the increased fracture risk can be modified by H1RA. 

PMID- 23973558
TI  - Reply to vorinostat induced bone loss in mice.

PMID- 23973559
TI  - Primary percutaneous thrombus aspiration alone as definitive intervention for
      left main coronary artery occlusion presenting as acute anterior wall ST
      elevation myocardial infarction.
AB  - Primary angioplasty and stenting remains the standard of care for patients
      presenting with acute ST-segment elevation myocardial infarction. Recently,
      thrombus aspiration has been shown to improve the myocardial perfusion and
      outcomes in STEMI. In a subset of patients thrombus aspiration may result in
      optimal perfusion and minimal residual stenosis. These patients may be managed
      without additional stenting. Three patients with anterior wall STEMI were
      successfully managed with thrombus aspiration alone without additional stenting.
      All three are doing well at 30 day follow up with significant improvement in left
      ventricular ejection fraction. 

PMID- 23973561
TI  - Using global maps to predict the risk of dengue in Europe.
AB  - This article attempts to quantify the risk to Europe of dengue, following the
      arrival and spread there of one of dengue's vector species Aedes (Stegomyia)
      albopictus. A global risk map for dengue is presented, based on a global database
      of the occurrence of this disease, derived from electronic literature searches.
      Remotely sensed satellite data (from NASA's MODIS series), interpolated
      meteorological data, predicted distribution maps of dengue's two main vector
      species, Aedes aegypti and Aedes albopictus, a digital elevation surface and
      human population density data were all used as potential predictor variables in a
      non-linear discriminant analysis modelling framework. One hundred bootstrap
      models were produced by randomly sub-sampling three different training sets for
      dengue fever, severe dengue (i.e. dengue haemorrhagic fever, DHF) and all-dengue,
      and output predictions were averaged to produce a single global risk map for each
      type of dengue. This paper concentrates on the all-dengue models. Key predictor
      variables were various thermal data layers, including both day- and night-time
      Land Surface Temperature, human population density, and a variety of rainfall
      variables. The relative importance of each may be shown visually using rainbow
      files and quantitatively using a ranking system. Vegetation Index variables (a
      common proxy for humidity or saturation deficit) were rarely chosen in the
      models. The kappa index of agreement indicated an excellent (dengue haemorrhagic
      fever, Cohen's kappa=0.79 +/- 0.028, AUC=0.96 +/- 0.007) or good fit of the top
      ten models in each series to the data (Cohen's kappa=0.73 +/- 0.018, AUC=0.94 +/-
      0.007 for dengue fever and 0.74 +/- 0.017, AUC=0.95 +/- 0.005 for all dengue).
      The global risk map predicts widespread dengue risk in SE Asia and India, in
      Central America and parts of coastal South America, but in relatively few regions
      of Africa. In many cases these are less extensive predictions than those of other
      published dengue risk maps and arise because of the key importance of high human
      population density for the all-dengue risk maps produced here. Three published
      dengue risk maps are compared using the Fleiss kappa index, and are shown to have
      only fair agreement globally (Fleiss kappa=0.377). Regionally the maps show
      greater (but still only moderate) agreement in SE Asia (Fleiss kappa=0.566), fair
      agreement in the Americas (Fleiss kappa=0.325) and only slight agreement in
      Africa (Fleiss kappa=0.095). The global dengue risk maps show that very few areas
      of rural Europe are presently suitable for dengue, but several major cities
      appear to be at some degree of risk, probably due to a combination of thermal
      conditions and high human population density, the top two variables in many
      models. Mahalanobis distance images were produced of Europe and the southern
      United States showing the distance in environmental rather than geographical
      space of each site from any site where dengue currently occurs. Parts of Europe
      are quite similar in Mahalanobis distance terms to parts of the southern United
      States, where dengue occurred in the recent past and which remain environmentally
      suitable for it. High standards of living rather than a changed environmental
      suitability keep dengue out of the USA. The threat of dengue to Europe at present
      is considered to be low but sufficiently uncertain to warrant monitoring in those
      areas of greatest predicted environmental suitability, especially in northern
      Italy and parts of Austria, Slovenia and Croatia, Bosnia and Herzegovina, Serbia
      and Montenegro, Albania, Greece, south-eastern France, Germany and Switzerland,
      and in smaller regions elsewhere.

PMID- 23973560
TI  - Enhanced taupathy and AD-like pathology in aged primate brains decades after
      infantile exposure to lead (Pb).
AB  - Late Onset Alzheimer Disease (LOAD) constitutes the majority of AD cases (~90%).
      Amyloidosis and tau pathology, which are present in AD brains, appear to be
      sporadic in nature. We have previously shown that infantile lead (Pb) exposure is
      associated with a change in the expression and regulation of the amyloid
      precursor protein (APP) and its beta amyloid (Abeta) products in old age. Here we
      report that infantile Pb exposure elevated the mRNA and protein levels of tau as
      well as its transcriptional regulators namely specificity protein 1 and 3 (Sp1
      and Sp3) in aged primates. These changes were also accompanied by an enhancement
      in site-specific tau phosphorylation as well as an increase in the mRNA and
      protein levels of cyclin dependent kinase 5 (cdk5). There was also a change in
      the protein ratio of p35/p25 with more Serine/Threonine phosphatase activity
      present in aged primates exposed to Pb as infants. These molecular alterations
      favored abundant tau phosphorylation and immunoreactivity in the frontal cortex
      of aged primates with prior Pb exposure. These findings provide more evidence
      that neurodegenerative diseases may be products of environmental influences that
      occur during the development. 

PMID- 23973562
TI  - Adaptation of the communicative brain to post-lingual deafness. Evidence from
      functional imaging.
AB  - Not having access to one sense profoundly modifies our interactions with the
      environment, in turn producing changes in brain organization. Deafness and its
      rehabilitation by cochlear implantation offer a unique model of brain adaptation
      during sensory deprivation and recovery. Functional imaging allows the study of
      brain plasticity as a function of the times of deafness and implantation. Even
      long after the end of the sensitive period for auditory brain physiological
      maturation, some plasticity may be observed. In this way the mature brain that
      becomes deaf after language acquisition can adapt to its modified sensory inputs.
      Oral communication difficulties induced by post-lingual deafness shape cortical
      reorganization of brain networks already specialized for processing oral
      language. Left hemisphere language specialization tends to be more preserved than
      functions of the right hemisphere. We hypothesize that the right hemisphere
      offers cognitive resources re-purposed to palliate difficulties in left
      hemisphere speech processing due to sensory and auditory memory degradation. If
      cochlear implantation is considered, this reorganization during deafness may
      influence speech understanding outcomes positively or negatively. Understanding
      brain plasticity during post-lingual deafness should thus inform the development
      of cognitive rehabilitation, which promotes positive reorganization of the brain
      networks that process oral language before surgery. This article is part of a
      Special Issue entitled Human Auditory Neuroimaging.

PMID- 23973563
TI  - Human auditory neuroimaging of intensity and loudness.
AB  - The physical intensity of a sound, usually expressed in dB on a logarithmic ratio
      scale, can easily be measured using technical equipment. Loudness is the
      perceptual correlate of sound intensity, and is usually determined by means of
      some sort of psychophysical scaling procedure. The interrelation of sound
      intensity and perceived loudness is still a matter of debate, and the
      physiological correlate of loudness perception in the human auditory pathway is
      not completely understood. Various studies indicate that the activation in human
      auditory cortex is more a representation of loudness sensation rather than of
      physical sound pressure level. This raises the questions (1), at what stage or
      stages in the ascending auditory pathway is the transformation of the physical
      stimulus into its perceptual correlate completed, and (2), to what extent other
      factors affecting individual loudness judgements might modulate the brain
      activation as registered by auditory neuroimaging. An overview is given about
      recent studies on the effects of sound intensity, duration, bandwidth and
      individual hearing status on the activation in the human auditory system, as
      measured by various approaches in auditory neuroimaging. This article is part of
      a Special Issue entitled Human Auditory Neuroimaging.

PMID- 23973564
TI  - Differences in phosphorylation of phosphoglucomutase 1 in beef steaks from the
      longissimus dorsi with high or low star probe values.
AB  - The objective of this study was to use proteomics to identify alterations of
      proteins that are related to tenderness. The longissimus dorsi (LD) were removed
      from ten beef carcasses at 24 h postmortem, and the two with the highest (HSP;
      average kg of force=6.57) and lowest star probe values (LSP; average kg of
      force=3.75) at 14 days postmortem were identified. Two-dimensional PAGE was used
      to compare the sarcoplasmic fraction of the LD from HSP and LSP steaks. A series
      of spots identified as phosphoglucomutase 1 (PGM1) were identified. Only the most
      alkaline isoform was identified as being unphosphorylated. The least
      phosphorylated isoform (isoform 5) had a greater density of the total protein
      (P<0.05) and phosphorylated protein (P<0.05) in the samples from HSP steaks
      compared to the samples from LSP steaks. This study illustrates the importance of
      identifying posttranslational modifications of proteins in the search for
      biomarkers.

PMID- 23973565
TI  - A novel approach to assess temporal sensory perception of muscle foods:
      application of a time-intensity technique to diverse Iberian meat products.
AB  - Although dynamic sensory techniques such as time-intensity (TI) have been applied
      to certain meat products, existing knowledge regarding the temporal sensory
      perception of muscle foods is still limited. The objective of the present study
      was to apply TI to the flavour and texture perception of three different Iberian
      meat products: liver pate, dry-cured sausages ("salchichon") and dry-cured loin.
      Moreover, the advantages of using dynamic versus static sensory techniques were
      explored by subjecting the same products to a quantitative descriptive analysis
      (QDA). TI was a suitable technique to assess the impact of composition and
      structure of the three meat products on flavour and texture perception from a
      dynamic perspective. TI parameters extracted from the TI-curves and related to
      temporal perception enabled the detection of clear differences in sensory
      temporal perception between the meat products and provided additional insight on
      sensory perception compared to the conventional static sensory technique (QDA). 

PMID- 23973566
TI  - Meat quality, proximate composition and muscle fatty acid profile of young llamas
      (Lama glama) supplemented with hay or concentrate during the dry season.
AB  - Thirty llamas were used to study the effect of a 90 day feed supplementation on
      meat quality, chemical composition and muscle fatty acid profile. Treatments
      were: GR=llama on native pasture until slaughter; GR+SH=like GR, but with
      overnight free access to barley/alfalfa hay; and GR+SC=like GR, but with
      overnight free access to a wheat bran/sorghum grain concentrate. The
      supplementation had no effect on postmortem pH and temperature decline in the
      Longissimus lumborum muscle (LLM), cooking losses nor Warner-Bratzler shear force
      values (P>0.05). Meat from GR+SC llama had higher fat content in LLM (P<0.05)
      compared to GR and GR+SH llama. Intramuscular fat from GR+SH llama showed higher
      (P<0.01) proportions of polyunsaturated fatty acids, higher (P<0.05)
      polyunsaturated fatty acids/saturated fatty acids and desirable fatty acids
      ratio, lower (P<0.05) omega-6/omega-3 (n-6/n-3) ratio, and higher (P<0.01)
      conjugated linoleic acid.

PMID- 23973567
TI  - Use of low dose e-beam irradiation to reduce E. coli O157:H7, non-O157 (VTEC) E.
      coli and Salmonella viability on meat surfaces.
AB  - This study determined the extent that irradiation of fresh beef surfaces with an
      absorbed dose of 1 kGy electron (e-) beam irradiation might reduce the viability
      of mixtures of O157 and non-O157 verotoxigenic Escherichia coli (VTEC) and
      Salmonella. These were grouped together based on similar resistances to
      irradiation and inoculated on beef surfaces (outside flat and inside round, top
      and bottom muscle cuts), and then e-beam irradiated. Salmonella serovars were
      most resistant to 1 kGy treatment, showing a reduction of <=1.9 log CFU/g. This
      treatment reduced the viability of two groups of non-O157 E. coli mixtures by
      <=4.5 and <=3.9 log CFU/g. Log reductions of <=4.0 log CFU/g were observed for E.
      coli O157:H7 cocktails. Since under normal processing conditions the levels of
      these pathogens on beef carcasses would be lower than the lethality caused by the
      treatment used, irradiation at 1 kGy would be expected to eliminate the hazard
      represented by VTEC E. coli.

PMID- 23973568
TI  - Effect of chronic treatment with angiotensin type 1 receptor antagonists on
      striatal dopamine levels in normal rats and in a rat model of Parkinson's disease
      treated with L-DOPA.
AB  - Beneficial effects of angiotensin type-1 receptor (AT1) inhibition have been
      observed in a number of brain processes mediated by oxidative stress and
      neuroinflammation, including Parkinson's disease. However, important
      counterregulatory interactions between dopamine and angiotensin systems have
      recently been demonstrated in several peripheral tissues, and it is possible that
      a decrease in dopamine levels due to AT1 inhibition may interfere with
      neuroprotective strategies. The present experiments involving rats with normal
      dopaminergic innervation indicate that chronic treatment with the AT1 antagonist
      candesartan does not significantly affect striatal levels of dopamine, serotonin
      or metabolites, as does not significantly affect motor behavior, as evaluated by
      the rotarod test. Interestingly, chronic administration of candesartan to normal
      rats induced a marked increase in dopamine D1 and a decrease in dopamine D2
      receptor expression. In a rat model of Parkinson's disease treated with L-DOPA,
      no differences in striatal dopamine and serotonin levels were observed between
      candesartan-treated rats and untreated, which suggests that chronic treatment
      with candesartan does not significantly affect the process of L-DOPA
      decarboxylation and dopamine release in Parkinson's disease patients. Candesartan
      did not induce any differences in the striatal expression of dopamine D1 and D2
      and serotonin 5-HT1B receptors in 6ydroxydopamine-lesioned rats treated with L
      DOPA. The results suggest that chronic treatment with AT1 antagonists as a
      neuroprotective strategy does not significantly affect striatal dopamine release
      or motor behavior. This article is part of the Special Issue entitled 'The
      Synaptic Basis of Neurodegenerative Disorders'.

PMID- 23973569
TI  - Parent adaptation and family functioning in relation to narratives of children
      with chronic illness.
AB  - BACKGROUND: This study assessed the experience of parents who have a child
      diagnosed with chronic illness and whether children's narratives mirror these
      experiences. METHOD: A total of 66 parents completed assessments about adaptation
      and family functioning. Children with type 1 diabetes or asthma participated in a
      story-stem narrative task. RESULTS: Forty-one percent of parents were unresolved
      about their child's diagnosis, regardless of time since diagnosis. Unresolved
      parents reported lower family functioning, and children in these families had
      more family conflict themes. CONCLUSIONS: Parental/Child narratives may provide
      unique insights into family adjustment. Future work may consider interventions
      related to family communication and expression of emotion.

PMID- 23973570
TI  - Development and validation of a quantitative real time PCR assay for BK virus.
AB  - Several studies have shown that BK viral load in plasma and urine are reliable
      markers for the detection of BK virus associated nephropathy (BKVAN) in renal
      transplant patients. We developed a quantitative real time PCR assay based on
      TaqMan technology for the measurement of BK viral load in plasma and urine.
      Considering the high similarity of the nucleotide sequence of the BK virus (BKV)
      with the JC virus (JCV), we designed this assay to specifically amplify BKV. We
      determined the viral DNA recovery rate on manual (QIAGEN's QIAamp DNA Blood Mini
      Kit) and automated (BioMerieux's NucliSENS EasyMAG) extraction methods. The
      comparison showed a higher viral DNA recovery rate on the automated extraction
      (61-76% in plasma and 52-65% in urine) as compared to the manual method (49-52%
      in plasma and 33-56% in urine). Quantitation of the viral load was performed
      using an external standard curve that was constructed with serial dilution of a
      plasmid containing the full length of the BKV genome. Commercially available
      quantitative BKV standards showed good correlation with the plasmid standard. The
      reproducibility of the assay was determined based on the Ct values of the
      amplified products as well as in BK copies per milliliter of sample. This assay
      is linear over a 7 log range (10 to 1 * 10(7) copies per reaction), no cross
      reactivity was detected with the closest-related polyomavirus JCV, as well as
      other viruses that may be found in immunocompromised patients, and human genomic
      DNA. The limit of detection of the assay is 300 copies per milliliter in both
      plasma and urine and the limit of quantitation is 1000 copies per milliliter
      using the NATtrol BK Virus Linearity Panel (ZeptoMetrix). This real time PCR
      assay provides a reliable and sensitive method for the quantitation of BKV in
      plasma and urine samples.

PMID- 23973571
TI  - Molecular complexes of l-phenylalanine with substituted 1,4-benzoquinones in
      aqueous medium: spectral and theoretical investigations.
AB  - Various spectral techniques such as UV-Vis, FT-IR, and fluorescence have been
      employed to investigate the charge transfer interaction of L-phenylalanine (LPA)
      with substituted 1,4-benzoquinones (MQ(1-4)). Kinetic and thermodynamic
      properties of the complexes were determined in aqueous medium at physiological
      condition (pH=7). The interaction of MQ(1-4) with L-phenylalanine (LPA) was found
      to proceed through the formation of donor-acceptor complex, yielding a radical
      anion. The stoichiometry of the complexes was determined by Jobs continuous
      variation method and was found to be 1:1 in all the cases. Fluorescence quenching
      studies showed that the interaction between the donor and the acceptors is
      spontaneous. The results indicated that the progressive replacement of chlorine
      atom (-I effect) by methoxy group (+M effect) in the quinone decreased the
      electron acceptor property of the quinone. The order of the experimentally
      measured association constant of these complexes was well supported by DFT/B3LYP
      calculations.

PMID- 23973572
TI  - Structural and optical properties of sol-gel synthesised Zn(1-x)Mg(x)O
      nanocrystals.
AB  - Zn(1-x)Mg(x)O nanocrystals with various compositions (x = 0-0.1) were synthesised
      by sol-gel process using tri ethanol amine (TEA) as a capping agent. The
      structural properties of the prepared materials were studied by X-ray diffraction
      analysis. Un-agglomerated nanocrystals with spherical morphology were observed by
      scanning electron microscope (SEM). The presence of Mg in the Zn(1-x)Mg(x)O was
      confirmed by X-ray photoelectron spectroscopy (XPS). Moreover, the Mg composition
      relatively increases in the synthesised nanocrystals as it increases in the
      precursor solution. The optical absorption studies of the Zn(1-x)Mg(x)O samples
      show the blue shift from the pure ZnO due to the incorporation of Mg in ZnO
      lattice. The photoluminescence studies demonstrated that the intensity of defect
      related deep level emission increases drastically with increasing the x value
      from 0.02 to 0.08 and decreases sharply on further increase of Mg from 0.08 to
      0.1. The mechanism for the enhanced green emission was explained based on the
      structural properties of the Zn(1-x)Mg(x)O samples.

PMID- 23973573
TI  - Temperature dependent luminescence of a europium complex incorporated in
      poly(methyl methacrylate).
AB  - An europium beta-diketonate complex with a dipyrazolyltriazine derivative ligand,
      Eu(TTA)3DPBT, has been incorporated into poly(methyl methacryate) (PMMA). The
      influence of temperature on its luminescence properties has been investigated.
      The fluorescence emission spectra and luminescence lifetimes showed temperature
      sensitivity. The analysis of the relative intensity ratio (R) of (5)D0 -> (7)F2
      to (5)D0 -> (7)F1 transition and Judd-Ofelt experimental intensity parameters
      Omega2 indicated that the local structure and asymmetry in the vicinity of
      europium ions show no obvious change when the temperature is increased.

PMID- 23973574
TI  - A kinetic study on the formation of poly(4 aminodiphenylamine)/copper
      nanocomposite using UV-visible spectroscopy.
AB  - The course of the reaction between copper sulfate (CuSO4) and 4
      aminodiphenylamine (4ADPA) was monitored by UV-visible spectroscopy in p-toluene
      sulfonic acid (p-TSA). Formation of poly(4-aminodiphenylamine)/copper
      nanoparticle composite (P4ADPA/CuNC) was witnessed through the steady increase in
      absorbance at 410, 580 and >700 nm. The absorbance at 410 nm as well as >700 nm
      are correlated to the amount of P4ADPA/CuNC formation and was subsequently used
      to determine the rate of formation of P4ADPA/CuNC (RP4ADPA/CuNC) at any time
      during the course of the reaction. RP4ADPA/CuNC shows a first-order dependence on
      [4ADPA] and a half-order dependence on [CuSO4]. A kinetic rate expression was
      established between RP4ADPA/CuNC and experimental parameters such as [4ADPA] and
      [CuSO4]. The rate constant for the formation of P4ADPA/CuNC was 8.98 * 10(-3)
      mol(-0.5) l(0.5) s(-1). Field emission scanning electron and transmission
      electron micrographs revealed that the morphology of the P4ADPA/CuNC was
      influenced by the reaction conditions.

PMID- 23973575
TI  - Functionalization of gold nanoparticles as antidiabetic nanomaterial.
AB  - In the present investigation, functionalization of gold nanoparticles synthesized
      using propanoic acid 2-(3-acetoxy-4,4,14-trimethylandrost-8-en-17-yl) (PAT) an
      active biocomponent isolated from Cassia auriculata is studied in detail. On
      reaction of PAT with aqueous HAuCl4, rapid formation of stable gold nanoparticles
      was achieved. Formation of gold nanoparticles was confirmed by UV-vis
      spectroscopy, XRD, GC-MS,FTIR, TEM and SEM with EDAX. Gold nanoparticles mostly
      were monodisperse, spherical in shape and ranged in size 12-41 nm. Gold
      nanoparticles synthesised using PAT was administered to alloxan (150 mg/kg body
      weight) induced diabetic male albino rats at different doses (0.25, 0.5, 0.75 and
      1.0mg/kg body weight) for 28 days. Plasma glucose level, cholesterol and
      triglyceride were significantly (p<0.001) reduced in experimental animals treated
      with gold nanoparticles at dosage of 0.5mg/kg body weight and plasma insulin
      increased significantly. The newly genre green gold nanoparticles exhibit
      remarkable protein tyrosine phosphatase 1B inhibitory activity.

PMID- 23973576
TI  - Surface enhanced Raman spectroscopy as a new spectral technique for quantitative
      detection of metal ions.
AB  - Four newly synthesized poly (propylene amine) dendrimers from first and second
      generation modified with 1,8-naphthalimide units in the dendrimer periphery have
      been investigated as ligands for the detection of heavy metal ions (Al(3+),
      Sb(2+), As(2+), Cd(2+) and Pb(2+)) by surface-enhanced Raman spectroscopy.
      Calibration curves were established for all metal ions between the concentration
      ranges of 1 x 10(-6) to 5 x 10(-4) M. It has been shown that these dendrimers can
      be coordinated, especially with different metal ions. Using dendrimer molecules
      and silver colloids at the same time allowed us to obtain an SERS signal from the
      abovementioned metal ions at very low concentrations. Principle component
      analysis (PCA) analysis was also applied to the collected SERS data. Four
      different PCA models were developed to accomplish the discrimination of five
      metal ions, which interacted with each of the four dendrimer molecules,
      separately. A detailed investigation was performed in the present study to
      provide the basis of a new approach for heavy metal detection.

PMID- 23973577
TI  - Syntheses, structures and properties of three new two-dimensional Cu(I)-Ln(III)
      heterometallic coordination polymers based on 2,2'-dipyridyl-5,5'-dicarboxylate
      ligands.
AB  - Three new two-dimensional Cu(I)-Ln(III) heterometallic coordination polymers
      [Ln(III)Cu2(I)(Hbpdc)4] . Cl . xH2O [Ln(III) = La(III), x = 8 (1); Ln(III) =
      Pr(III), x=9 (2); Ln(III) = Eu(III), x = 8 (3)] (H2bpdc = 2,2'-bipyridyl-5,5'
      dicarboxylic acid) have been prepared under hydrothermal conditions and
      structurally characterized by elemental analyses, inductively coupled plasma
      atomic emission spectrometry (ICP-AES) analyses, IR spectra, X-ray photoelectron
      spectroscopy (XPS) and single-crystal X-ray diffraction. X-ray diffraction
      indicates that the isomorphic 1-3 display the two-dimensional sheet structure
      constructed from [Cu(I)(Hbpdc)2](-) fragments through Ln(3+) connectors.
      Moreover, the solid-state photoluminescence measurements of 3 indicate that the
      Eu(III) ions, Hbpdc(-) ligands and Cu(I) cations make contributions to its
      luminescent properties simultaneously.

PMID- 23973578
TI  - Plasmonic luminescent core-shell nanocomposites-enhanced chemiluminescence
      arising from the decomposition of peroxomonosulfite.
AB  - A core-shell structure of plasmonic luminescent nanocomposite, Ni@SiO2@FITC@SiO2
      (NSFS) combining the stable luminescence of fluorophore with the excellent
      plasmonic property of metal nanomaterials, has been synthesized through layer-by
      layer assembly. The effect of NSFS on the ultraweak chemiluminescence (CL)
      reaction of hydrogen peroxide (H2O2) and sodium bisulfite (NaHSO3) was explored
      for the first time. It was found that the CL intensity from the decomposition of
      peroxomonosulfite was significantly enhanced by NSFS. The mechanism of the
      nanocomposite-enhanced CL was revealed as the coupling of chemically induced
      excited states of fluorescein isothiocyanate (FITC) with surface plasmons of Ni
      nanoparticles based on studies of CL emission spectra, electron spin resonance
      spectra, extinction spectra and fluorescence spectra. The work sheds new light on
      the characteristics of the versatile materials and gives us new insight into the
      optical properties of fluorophores. 

PMID- 23973579
TI  - Electrogenerated chemiluminescence detector based on Ru(bpy)3(2+) immobilized in
      cation exchange resin for high-performance liquid chromatography: An approach to
      stable detection.
AB  - In this work, an electrogenerated chemiluminescence (ECL) detector with improved
      stability was developed for high-performance liquid chromatography (HPLC)
      detection of hydrochlorothiazide (HCTZ). The detector was prepared by packing
      cation exchanged resin particles in a glass tube, followed by inserting Pt wires
      (working electrode) in this tube and sealing. The leakage of Ru(bpy)3(2+) from
      the resin was compensated by adding a small amount of Ru(bpy)3(2+) in the mobile
      phase. Factors affected the performance of the proposed ECL detector were
      investigated. Under the optimal conditions, the ECL intensity has a linear
      relationship with the concentration of HCTZ in the range of 5.0 * 10(-8) g mL(-1)
      2.5 * 10(-5) g mL(-1) and the detection limit was 2.0 * 10(-8) g mL(-1) (S/N=3).
      Application of the detector to the analysis of HCTZ in human serum proved
      feasible.

PMID- 23973580
TI  - Comparison of serum from gastric cancer patients and from healthy persons using
      FTIR spectroscopy.
AB  - Since serum can reflect human beings' physiological and pathological conditions,
      FTIR spectroscopy was used to compare gastric cancer patients' serum with healthy
      persons' serum in this study. The H2959/H2931, H1646/H1550, H1314/H1243,
      H1453/H1400 and H1080/H1550 ratios were calculated, among these ratios, the
      H2959/H2931 ratio might be a standard for distinguishing gastric cancer patients
      from healthy persons. Then curve fitting was processed using Gaussian curves in
      the 1140-1000 cm(-1) region, and the result showed that the RNA/DNA ratios of
      gastric cancer patients' serum were obviously lower than those of healthy
      persons' serum. The results suggest that FTIR spectroscopy may be a potentially
      useful tool for diagnosis of gastric cancer.

PMID- 23973581
TI  - Rapid determination of immunoglobulin G concentration in cold ethanol
      precipitation process of raw plasma with near-infrared spectroscopy.
AB  - Near-infrared spectroscopy (NIRS) is known to be a powerful analytical tool in
      process monitoring. The feasibility of NIRS was investigated for determination of
      immunoglobulin G (IgG) in raw plasma cold ethanol precipitation process. Partial
      least squares (PLS) was used to develop regression model for 63 samples between
      spectra and reference data measured with a UV spectrophotometer. Three different
      variable selection methods, including correlation coefficient method, interval
      partial least squares (iPLS) and successive projection algorithm (SPA), were
      performed and compared with models based on all the variables. The values of Rc
      and root mean square error of cross validation (RMSECV) produced by the best
      model for the calibration set were 0.9599 and 0.6135 g/L, respectively. While for
      the validation set, the values of Rp and root mean square error of prediction
      (RMSEP) were 0.9577 and 0.4913 g/L, respectively. The results of this paper
      demonstrated that NIRS could be a feasible alternative approach for rapid
      determination of IgG in the cold ethanol precipitation process and can be used as
      a PAT tool in the future.

PMID- 23973582
TI  - Fabrication, characterization of two nano-composite CuO-ZnO working electrodes
      for dye-sensitized solar cell.
AB  - Two kind of CuO-ZnO nanocomposite working electrodes were synthesized by sol-gel
      technology and applied in dye-sensitized solar cells (DSSCs). Their
      characteristics were studied by field emission scanning electron microscopy
      (FESEM), X-ray diffraction (XRD) and UV-Vis diffuse reflectance spectrum (DRS).
      CuO-ZnO nanocomposite thin films were prepared doctor blade technique on the
      fluorine-doped tin oxide (FTO) and used as working electrodes in dye sensitized
      solar cells (DSSC). Their photovoltaic behavior were compared with standard using
      D35 dye and an electrolyte containing [Co(bpy)3](PF6)2, [Co(pby)3](PF6)3, LiClO4,
      and 4-tert-butylpyridine (TBP). The ranges of short-circuit current (JSC) from
      0.18 to 0.21 (mA/cm(2)), open-circuit voltage (VOC) from 0.24 to 0.55V, and fill
      factor from 0.34 to 0.39 were obtained for the DSSCs made using the working
      electrodes. The efficiency of the working electrodes after the addition of TBL
      was more than doubled. The light scattering and carrier transport properties of
      these composites promote the performance of dye-sensitized solar cells (DSSCs). 

PMID- 23973583
TI  - Raman spectroscopic and ab initio studies on the molecular interactions in the
      binary liquid mixtures of 4'-fluoroacetophenone.
AB  - Raman spectral measurements were carried out for binary liquid mixtures
      4'fluoroacetophenone (4F) in different volume concentration ranges at a regular
      intervals of 0.1 in different solvents. The asymmetric Raman peak observed at
      1685 cm(-1) (carbonyl stretching mode) in pure 4F confirms the presence of self
      association in 4F. The optimization was performed for monomer and dimer
      structures of 4F as well as 4F dimer with solvents using Gaussian 03 W package.
      Vibrational wavenumber calculation was performed for monomer and dimer structures
      of 4F to explain the experimentally observed Raman spectra. The carbonyl
      stretching mode is the more polar group and its interaction with the solvent
      molecule plays a vital role in determining the physical and chemical properties
      of the solute. Hence the observed variation in the peak position and linewidth of
      carbonyl stretching mode was analysed as a result of intermolecular interactions
      between the solute and the solvent molecules. Also, interaction energies were
      calculated to support the results obtained from Raman spectra.

PMID- 23973584
TI  - Three hydroxy aurone compounds as chemosensors for cyanide anions.
AB  - Three new 4-hydroxy aurone compounds 1-3 with dimethylamino (1), bromine (2) and
      cyano (3) as terminal group have been synthesized. Their photophysical properties
      as well as recognition properties for cyanide anions in acetonitrile and aqueous
      solution have also been examined. These compounds exhibit remarkable response to
      cyanide anions with obvious color and fluorescence change owing to hydrogen
      bonding reaction between cyanide anions and the O-H moiety of the sensors, which
      allows naked eye detection of cyanide anions. 

PMID- 23973585
TI  - Synthesis, characterization and biological studies of some novel 3
      fluorosalicylaldehyde based amine derivatives.
AB  - A series of biologically important substituted 3-fluorosalicylaldehyde
      derivatives (1a-h) with various primary amines were synthesized by using ionic
      liquid (1-Butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) as an
      efficient catalyst. A new series of Schiff base derivatives (1a-h) were
      synthesized and characterized by IR, NMR ((1)H, (13)C, (1)H-(1)H COSY and HSQC),
      mass spectra and elemental analysis. Further crystal structure of compound 1a was
      evaluated by single crystal X-ray diffraction techniques. All the synthesized
      compounds were screened for in vitro antimicrobial activity against a panel of
      selected bacterial and fungal strains using Streptomycin and Amphotericin B as
      standards. Most of the synthesized compounds demonstrated moderate effects on
      both antibacterial and antifungal activities at minimum inhibitory concentrations
      (MIC's). 

PMID- 23973586
TI  - Structural comparative studies on new Mn(II), Cr(III) and Ru(III) complexes
      derived from 2,4,6-tri-(2-pyridyl)-1,3,5-triazine (TPTZ).
AB  - The structure of a new Mn(II) complex, [Mn(TPTZ)Cl2(H2O)]?H2O, was established by
      a single crystal X-ray diffraction. Crystal data are as follow: monoclinic,
      P21/c,a = 8.7202 (3)A, b = 11.5712 (4)A, c = 20.8675 (9)A, beta=11 (18) * 1010, V
      = 2029.27 (13)A(3), Z = 4. The HOMO, LUMO and other DFT parameters on the atoms
      have been calculated to confirm the geometry of the ligand and its complexes
      using material studio program. The complexes were characterized by elemental
      analyses, spectral, magnetic, thermal and cyclic voltammetry measurements.
      Electronic spectra and magnetic moments of the complexes suggest distorted
      octahedral structures around the metal ions (Mn(II), Cr(III) and Ru(III)). The
      redox properties were investigated by cyclic voltammetry. Kinetic parameters were
      determined using Coats-Redfern and Horowitz-Metzger methods. The results of DNA
      studies of the metal complexes promised to be effective in tumour treatment.

PMID- 23973587
TI  - Experimental determinations and quantum-chemical calculations of the vibrational
      spectra of beta-ZnB4O7 and beta-CaB4O7.
AB  - The two oxoborates beta-ZnB4O7 and beta-CaB4O7 were synthesized and investigated
      by FTIR- and Raman spectroscopy and ab initio quantum chemical calculations.
      Maximum and mean deviations between experimentally determined bands and
      calculated modes ranged between 15-36 cm(-1) and 5-7 cm(-1), respectively,
      allowing band assignments to vibrational modes in most cases. The complex network
      structures with tetrahedral BO4 and planar OB3 groups are mirrored by the spectra
      and numerous vibrational modes, not assignable by standard borates classification
      schemes. It was confirmed that OB3 units, despite similar force constants and
      geometry, do not absorb in the same range as BO3 units. Bands in the high
      wavenumber range are rather caused by B-O-(Zn/Ca), O-B-O, B-O-B, and B-O
      stretching and bending vibrations. The experimental observation of inactive or
      Raman-active modes in the absorption spectra indicates defects or structural
      distortions in both compounds.

PMID- 23973588
TI  - N,N-di(2-pyridylmethyl)amino-modified porphyrinato zinc complexes. The "ON-OFF"
      fluorescence sensor for Fe3+.
AB  - Two porphyrinato-zinc derivatives modified with two and four N,N-di(2
      pyridylmethyl)amino groups, namely Zn-Porphyrin-2-DPA (1) and Zn-Porphyrin-4-DPA
      (2), have been designed, synthesized, and characterized. Systemic studies over a
      series of metal ions reveal that binding with Fe(3+) for the former compound
      induces the decrease of fluorescence emission intensity by 37.2%, while for the
      latter one results in a more remarkable decrease in the fluorescence emission
      intensity by 90.3%, rendering compound 2 the first example of DPA-modified
      porphyrin fluorescence ON-OFF sensor for Fe(3+). 

PMID- 23973589
TI  - Biosynthesis of silver nanoparticle from leaf extract of Desmodium gangeticum
      (L.) DC. and its biomedical potential.
AB  - An aqueous leaf extract of Desmodium gangeticum was employed to synthesize silver
      nano particles. Rapid formation of stable silver nanoparticles were observed on
      exposure of the aqueous leaf extract with solution of silver nitrate. The silver
      nanoparticles were characterized by UV-visible spectroscopy, scanning electron
      microscopy, energy dispersive X-ray analysis and transmission electron microscopy
      (TEM), and Fourier Transform Infra-Red spectroscopy (FTIR) UV-visible
      spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray
      analysis (EDAX), transmission electron microscopy (TEM), and Fourier Transform
      Infra-Red spectroscopy (FTIR). UV-visible spectrum of the aqueous medium peaked
      at 450 nm corresponding to the plasmon absorbance of silver nanoparticles. SEM
      analysis revealed the spherical shape of the particles with sizes ranging from 18
      to 39 nm and the EDAX spectrum confirmed the presence of silver along with other
      elements in the plant metabolite. Further, these biologically synthesized
      nanoparticles were found to be highly toxic against pathogenic bacteria
      Escherichia coli, thus implying significance of the present study in production
      of biomedical products.

PMID- 23973590
TI  - Supramolecular spectral studies on metal-ligand bonding of novel quinoline
      azodyes.
AB  - A series of novel bidentate azodye quinoline ligands were synthesized with
      various p-aromatic amines like p-(OCH3, CH3, H, Cl and NO2). All ligands and
      their complexes have been characterized on the basis of elemental analysis, IR,
      (1)H and (13)C NMR data and spectroscopic studies. IR and (1)H NMR studies reveal
      that the ligands (HLn) exists in the tautomeric azo/hydrazo form in both states
      with intramolecular hydrogen bonding. The ligands obtained contain NN and
      phenolic functional groups in different positions with respect to the quinoline
      group. IR spectra show that the azo compounds (HLn) act as monobasic bidentate
      ligand by coordinating via the azodye (NN) and oxygen atom of the phenolic group.
      The ESR (g|| and g ) and bonding alpha(2) parameters of the copper ion were
      greatly affected by substituting several groups position of ring of quinoline and
      p-aromatic ring. The ESR spectra of copper complexes in powder form show a broad
      signal with values in order g|| >g > ge > 2.0023. The value of covalency factor
      beta and orbital reduction factor K accounts for the covalent nature of the
      complexes. All complexes possessed an octahedral and square planar geometry. The
      thermal properties of the complexes were investigated using TGA and DSC. It is
      found that the change of substituent affects the thermal properties of complexes.

PMID- 23973591
TI  - Determination of ethylenediaminetetraacetic acid base on the reversion of
      fluorescence quenching of 2-pyridinecarbaldehyde-p-phenyldihydrazone by ferric
      iron.
AB  - A fast and sensitive fluorometric method for determination of an emerging
      pollutant, ethylenediaminetetraacetic acid (EDTA), was proposed based on the
      reversion of fluorescence quenching of 2-pyridinecarbaldehyde-p-phenyldihydrazone
      by ferric iron. It was found that Fe(3+) could selectively quench the
      fluorescence of 2PC-PPH, while EDTA could recover it due to its strong
      coordination ability with Fe(3+). Based on this, we established an "Off and On"
      fluorescence method for determination of EDTA. Under the optimum conditions, the
      linear range and detection limit (3S/N) for EDTA determination were 2.0 * 10(
      6)~1.4 * 10(-5) mol L(-1) and 1.5 * 10(-7) mol L(-1), respectively. The relative
      standard deviation for the determination of 7.0 * 10(-6)mol L(-1) EDTA was 3.7%
      (n=11). The method was successfully applied to determination of EDTA in tap
      water, lake water and investigating degradation of EDTA by TiO2/UV process.

PMID- 23973592
TI  - IR laser induced spectra in novel crystals CdTe-CuInTe2.
AB  - The novel crystalline alloys CdTe-CuInTe2 were synthesized. The photoinduced
      spectral changes of the anharmonic phonon modes were explored by cw CO2 laser at
      power about 2 kW in the vicinity of the 1650 cm(-1) mode. The changes of the
      intensities for principal phonon modes were found. These modes were assigned both
      to harmonic as well as anharmonic modes. All the measurements are studied after
      the Ir illumination. The performed quantum chemical calculations with application
      of the norm-conserving pseudopotential method and Green functions allow to
      identify the origin of the content dependent anharmonic phonon modes. Some
      correlation between the intensities of the corresponding phonon modes at about
      1600-1700 cm(-1) and the corresponding IR induced changes were found.

PMID- 23973593
TI  - The infrared, Raman, NMR and UV spectra, ab initio calculations and spectral
      assignments of 2-amino-4-chloro-6-methoxypyrimidine.
AB  - The 2-amino-4-chloro-6-methoxypyrimidine abbreviated as ACMP have been
      investigated by both the experimental and theoretical methods; through this work
      we provide the essential fact about the structural and vibrational insights. The
      optimized molecular structure, atomic charges, vibrational frequencies and
      ultraviolet spectral interpretation of ACMP have been studied by performing
      DFT/B3LYP/6-311++G(df,pd) level of theory. The FT-IR, FT-Raman spectra were
      recorded in the region 4000-400 cm(-1) and 4000-50 cm(-1) respectively. The UV
      absorption spectrum of the compound that dissolved in ethanol and water solution
      were recorded in the range of 200-400 nm. The scaled wavenumbers are compared
      with the experimental values. The difference between the observed and scaled
      wavenumber values of most of the fundamentals is very small. Based on the UV
      spectrum and TD-DFT calculations, the electronic structure and the assignments of
      the absorption bands were carried out. The (1)H, (13)C and DEPT 135 nuclear
      magnetic resonance (NMR) chemical shifts of the molecule were calculated using
      with the Gauge Including Atomic Orbital (GIAO) method and compared with
      experimental results. Besides, molecular electrostatic potential (MEP), frontier
      molecular orbitals (FMO) analysis were investigated using theoretical
      calculations.

PMID- 23973594
TI  - Glutamine-containing "turn-on" fluorescence sensor for the highly sensitive and
      selective detection of chromium (III) ion in water.
AB  - In this study, we reported a new fluorescence sensor for chromium (III) ion,
      dansyl-L-glutamine (1). The sensor displayed a unique selective fluorescence
      "turn-on" response to Cr(3+) over other common metal ions in water. Notably, 1
      still showed a ratiometric response to Cr(3+) in UV-vis absorption spectra. The
      binding mechanism of 1 to Cr(3+) was further clarified by using NMR and ESI-MS
      spectra. The experiment results indicated that the dual-responses of 1 to Cr(3+)
      should attribute to the coordination of deprotonated sulfonamide group with
      Cr(3+) and the protonation of the dimethylamino group due to the coordination of
      Cr(3+) for 1. In addition, two chloride ions also coordinated to the complex of
      sensor-chromium (III) ion, which further strengthened the conformation of 1
      Cr(3+). 

PMID- 23973595
TI  - Photophysics of Soret-excited free base tetraphenylporphyrin and its zinc analog
      in solution.
AB  - Photophysical properties of free base tetraphenylporphyrin and its zinc analog
      are investigated in detail in solvents of varying polarity by using steady state
      and time-resolved techniques. Both the porphyrins are excited at the Soret band
      to have better signal-to-noise ratio. Also, the fluorescence emission
      measurements are carried out by using dilute solutions (~10(-7)mol/L) of the
      fluorophores in order to minimize the self-quenching effect. It is observed that
      the steady state absorption and emission characteristics of the porphyrin
      molecules are mainly affected by polarizability (via refractive index) rather
      than polarity (via dielectric constant) of the moderate to highly polar solvents.
      As the molecules are highly symmetric in the ground state, the associated dipole
      moments are found to be very low from quantum chemical calculations performed by
      density functional theory method by using Gaussian 03 package. The dipole moments
      associated with the first excited singlet state of the porphyrins are computed by
      applying solvatochromic Stokes' shift method. To the best of our knowledge, this
      is the first attempt to calculate the excited state dipole moments of the
      porphyrins used in the present investigations. Also, fluorescence quantum yield,
      fluorescence lifetime of the first excited singlet state, radiative and non
      radiative rate constants of the porphyrins are reported in solvents of varying
      polarity.

PMID- 23973596
TI  - Synthesis, photophysical, electrochemical and electroluminescent properties of a
      novel iridium(III) complex based on 2-phenylbenzo[d]oxazole derivative.
AB  - A new phosphorescent iridium (III) complex based on 2-(4-tert-butylphenyl)-5
      methylbenzo[d]oxazole as main ligand, i.e. bis(2-(4-tert-butylphenyl)-5
      methylbenzo[d]oxazole-N,C(2'))iridium(acetylacetonate) [(tmbo)2Ir(acac)], was
      synthesized for organic light-emitting diodes (OLEDs), and its photophysical,
      electrochemical and electroluminescent properties were investigated. The complex
      displayed strong phosphorescence emission, high decomposition temperature, short
      phosphorescent lifetime and reversible redox electrochemical behavior. The OLEDs
      based on (tmbo)2Ir(acac) as dopant emitter exhibited maximum luminance efficiency
      of 26.1cdA(-1) and high luminance of 16,445 cd m(-2). Interestingly, highly doped
      device based on (tmbo)2Ir(acac) showed high efficiency with negligible roll-off
      under a wide range of driving current density, which was mainly attributed to the
      effect of bulky steric hindrance of multi-methyl groups on this complex and its
      short phosphorescent lifetime.

PMID- 23973597
TI  - Identification and discrimination of bacteria using Fourier transform infrared
      spectroscopy.
AB  - Bacterial spectra were obtained in the wavenumber range of 4000-600 cm(-1) using
      FTIR spectroscopy. FTIR spectral patterns were analyzed and matched with 16S-rRNA
      signatures of bacterial strains OS1 and OS2, isolated from oil sludge. Specific
      spectral bands obtained from OS1 (FJ226761), reference strain Bacillus flexus
      (ATCC 49095), OS2 (FJ215874) and reference strain Stenotrophomonas maltophilia
      (ATCC 19861) respectively, suggested that OS1 and ATCC 49095 were closely related
      whereas OS2 was different. The bands probably represent groups of proteins and
      lipids of specific bacteria. Separate peaks found in B. flexus were similar to
      those of OS1. The S. maltophilia (ATCC 19861) and OS2 exhibited a similar peak at
      3272 cm(-1). Amide bands (I, II and III) exhibited that OS1 and B. flexus were
      closely related, but were different from OS2. In the fingerprint region, peak at
      1096 cm(-1) and 1360 cm(-1) exhibited the specific fingerprints of OS2 and
      reference strain S. maltophilia (ATCC 19861), respectively. The specific
      fingerprint signature was found at 1339 cm(-1) for OS1 and at 1382 cm(-1) for B.
      flexus ATCC 49095, allowing these two strains of B. flexus to be differentiated.
      This spectral signature originated from phospholipid and RNA components of the
      cell. Principle components analysis (PCA) of spectral regions exhibited with
      distinct sample clusters between Bacillus flexus (ATCC 49095), S. maltophilia
      (ATCC 19861), OS1 and OS2 in amide and fingerprint region.

PMID- 23973598
TI  - Extracellular synthesis of mycogenic silver nanoparticles by Cylindrocladium
      floridanum and its homogeneous catalytic degradation of 4-nitrophenol.
AB  - Green synthesis of extracellular mycogenic silver nanoparticles using the fungus,
      Cylindrocladium floridanum is reported. The synthesized mycogenic silver
      nanoparticles were characterized using UV-Vis absorption spectroscopy, X-ray
      diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray
      spectroscopy (EDX), and transmission electron microscopy (TEM) techniques. The
      nanoparticles exhibit fcc structure with Bragg's reflections of (111), (200),
      (220) and (311) was evidenced by XRD pattern, high-resolution TEM lattice fringes
      and circular rings in selected-area electron diffraction (SAED) pattern. The
      morphology of nanoparticles was roughly spherical in shape with an average size
      of ca. 25 nm. From FTIR spectrum, it was found that the biomolecules with amide I
      and II band were involved in the stabilization of nanoparticles. These mycogenic
      silver nanoparticles exhibited the homogeneous catalytic potential in the
      reduction of pollutant, 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) using sodium
      borohydride, which followed a pseudo-first-order kinetic model. Thus, the
      synthesis of metal nanoparticles using sustainable microbial approach opens up
      possibilities in the usage of mycogenic metal nanoparticles as catalysts in
      various chemical reactions.

PMID- 23973599
TI  - Raman and infrared spectroscopic characterization of the phosphate mineral
      paravauxite Fe2+Al2(PO4)2(OH)2.8H2O.
AB  - We have undertaken a vibrational spectroscopic study of paravauxite the Siglo XX
      mine, Bustillo Province, northern of Potosi department, Bolivia. This mine is
      important source for rare and unusual secondary phosphate minerals and is the
      type locality for a number of rare phosphates such as vauxite, sigloite,
      metavauxite and for jeanbandyite. The chemical formula of the studied sample was
      determined as Fe(2+)(0.9)5, Al(0.07)Sigma1.02 (Al)2.09 (PO4)1:97 (OH)1.98 .
      7.90(H2O). The Raman spectrum is dominated by an intense Raman band at 1020 cm(
      1) assigned to the PO4(3-) nu1 symmetric stretching mode. Low intensity Raman
      bands found at 1058, 1115 and 1148 cm(-1) are assigned to the PO4(3-) nu3
      antisymmetric stretching vibrations. Raman bands of paravauxite at 537, 570, 609
      and 643 cm(-1) are assigned to the nu4 PO4(3-) bending modes whilst the Raman
      bands at 393 and 420 cm(-1) are due to the nu2 PO4(3-) bending modes. The Raman
      spectral profile of paravauxite in the hydroxyl stretching region is broad with
      component bands resolved at 3086, 3215, 3315, 3421, 3505 and 3648 cm(-1).
      Vibrational spectroscopy enables the assessment of the molecular structure of
      paravauxite to be undertaken.

PMID- 23973600
TI  - A novel 2-(2-Formyl-4-methyl-phenoxy)-N-phenyl-acetamide-based fluorescence turn
      on chemosensor for selenium determination with high selectivity and sensitivity.
AB  - A novel turn-on fluorescent chemosensor, 2-(2-Formyl-4-methyl-phenoxy)-N-phenyl
      acetamide (FMPPA) was designed and synthesized, and its photophysical properties
      were characterized. Upon coordination with Se (IV), the chemosensor showed
      incredible fluorescence enhancement (turn-on), other alkali, alkaline earth,
      transitional metal ions, and common anions including Li(+), Na(+), K(+), Rb(+),
      Cs(+), Be(2+), Mg(2+), Ca(2+), Sr(2+), Ba(2+), Ni(2+), Cu(2+), Cd(2+), Zn(2+),
      Mn(2+), As(3+), Pt(4+), V(5+), Fe(3+), Mo(6+), Al(3+), CO3(2-), Cl(-), SCN(-),
      AC(-), NO3(-), F(-), SO4(2-) had no significant interference on Se (IV)
      determination. The chemosensor exhibits a dynamic response range for Se (IV) from
      3.32 * 10(-7) to 2.63 * 10(-6)M, with a detection limit of 9.38 * 10(-9)M
      (3sigma).

PMID- 23973601
TI  - Infrared and Raman spectroscopic characterization of the arsenate mineral
      ceruleite Cu2Al7(AsO4)4(OH)13. 11.5(H2O).
AB  - The molecular structure of the arsenate mineral ceruleite has been assessed using
      a combination of Raman and infrared spectroscopy. The most intense band observed
      at 903 cm(-1) is assigned to the (AsO4)(3-) symmetric stretching vibrational
      mode. The infrared spectrum shows intense bands at 787, 827 and 886 cm(-1),
      ascribed to the triply degenerate nu3 antisymmetric stretching vibration. Raman
      bands observed at 373, 400, 417 and 430 cm(-1) are attributed to the nu2
      vibrational mode. Three broad bands for ceruleite found at 3056, 3198 and 3384
      cm(-1) are assigned to water OH stretching bands. By using a Libowitzky empirical
      equation, hydrogen bond distances of 2.65 and 2.75A are calculated. Vibrational
      spectra enable the molecular structure of the ceruleite mineral to be determined
      and whilst similarities exist in the spectral patterns with the roselite mineral
      group, sufficient differences exist to be able to determine the identification of
      the minerals.

PMID- 23973602
TI  - Detection of compatibility between baclofen and excipients with aid of infrared
      spectroscopy and chemometry.
AB  - In the paper infrared (IR) spectroscopy and multivariate exploration techniques:
      principal component analysis (PCA) and cluster analysis (CA) were applied as
      supportive methods for the detection of physicochemical incompatibilities between
      baclofen and excipients. In the course of research, the most useful rotational
      strategy in PCA proved to be varimax normalized, while in CA Ward's hierarchical
      agglomeration with Euclidean distance measure enabled to yield the most
      interpretable results. Chemometrical calculations confirmed the suitability of
      PCA and CA as the auxiliary methods for interpretation of infrared spectra in
      order to recognize whether compatibilities or incompatibilities between active
      substance and excipients occur. On the basis of IR spectra and the results of PCA
      and CA it was possible to demonstrate that the presence of lactose, beta
      cyclodextrin and meglumine in binary mixtures produce interactions with baclofen.
      The results were verified using differential scanning calorimetry, differential
      thermal analysis, thermogravimetry/differential thermogravimetry and X-ray powder
      diffraction analyses. 

PMID- 23973603
TI  - Green synthesis of size controllable gold nanoparticles.
AB  - A facile rapid green eco-friendly method to synthesize gold nanoparticles (Au
      NPs) of tunable size using aqueous Terminalia arjuna fruit extracts has been
      demonstrated herein. Formation of Au NPs was confirmed by Surface Plasmon
      Resonance (SPR) study at 528 nm using UV-visible spectrophotometer. The time of
      reduction, size and morphological variations of Au NPs were studied with varying
      quantities of T. arjuna fruit aqueous extracts. Synthesized Au NPs were
      characterized using UV-visible spectroscopy, Fourier transformed infrared
      spectroscopy (FT-IR), powder X-ray diffraction (XRD), transmission electron
      microscopy (TEM) and Energy dispersive X-ray spectroscopy (EDAX). Polyphenols
      responsible for reduction of Au(3+) to Au(0) were identified using High
      Performance Liquid Chromatography (HPLC) as ascorbic acid, gallic acid and
      pyrogallol. The oxidized forms of polyphenols formed coordination with surface of
      Au NPs which protected their further growth and aggregation. We also propose a
      plausible mechanism how to tune size and shape of Au NPs by varying the quantity
      of extracts. Thus obtained Au NPs were stable for more than four months.

PMID- 23973604
TI  - Color tunable emission in Ce3+ and Tb3+ co-doped Ba2Ln(BO3)2Cl (Ln=Gd and Y)
      phosphors for white light-emitting diodes.
AB  - Ce(3+) and Tb(3+) co-doped Ba2Ln(BO3)2Cl (Ln=Y and Gd) green emitting phosphors
      were prepared by solid state reaction in reductive atmosphere. The emission and
      excitation spectra as well as luminescence decays were investigated, showing the
      occurrence of efficient energy transfer from Ce(3+) to Tb(3+) in this system. The
      phosphors exhibit both a blue emission from Ce(3+) and a green emission from
      Tb(3+) under near ultraviolet light excitation with 325-375 nm wavelength.
      Emission colors of phosphors could be tuned from deep blue through cyan to green
      by adjusting the Tb(3+) concentrations. The energy transfer efficiency and
      emission intensity of Ba2Y(BO3)2Cl:Ce(3+), Tb(3+) precede those of
      Ba2Gd(BO3)2Cl:Ce(3+), Tb(3+), and the sample Ba2Y(BO3)2Cl:0.03Ce(3+), 0.10Tb(3+)
      is the best candidate for n-UV LEDs.

PMID- 23973605
TI  - Calmodulin-dependent regulation of neurotransmitter release differs in subsets of
      neuronal cells.
AB  - The purpose of this study was to determine whether calmodulin (CaM) plays a role
      in neurotransmitter release by examining the effect that ophiobolin A (OBA), a
      CaM antagonist, on neurotransmitter release from clonal rat pheochromocytoma PC12
      cells, primary cortical neurons, and primary cerebellar granule cells. OBA
      inhibited Ca2+/CaM-dependent phosphorylation of cAMP response element binding
      protein in all cell types tested. Moreover, Ca2+-dependent release of dopamine
      and acetylcholine from PC12 cells were remarkably reduced by OBA in a dose
      dependent and temporal manner, but neurotransmitter release partially recovered
      with the addition of CaM in membrane permeabilized PC12 cells. OBA and several
      synthetic CaM antagonists suppressed Ca2+-dependent glutamate release from
      cerebral cortical neurons, but not from cerebellar granule cells. Myosin Va, a
      CaM binding protein, localized to synaptic vesicles of PC12 cells and cerebral
      cortical neurons, but not in cerebellar granule cells. OBA suppressed Ca2+
      induced myosin Va dissociation from secretory vesicles, and inhibited secretory
      vesicle motility in PC12 cells. These results suggest that CaM, although not
      essential, regulates neurotransmitter release in a subset of neurons and
      secretory cells, and myosin Va is a possible target of OBA in this process.

PMID- 23973606
TI  - Excitotoxic lesion of the hippocampus of Wistar rats disrupts the circadian
      control of the latent inhibition of taste aversion learning.
AB  - Previous experiments have shown that changes in the time of day between taste pre
      exposure and conditioning prevent the latent inhibition of conditioning taste
      aversion. The effect of these changes in circadian context between pre-exposure
      and conditioning on the magnitude of the learned aversion appears to be similar
      to the effect of changes in spatial context on this type of learning. To
      elucidate the brain areas involved in this circadian dependence of latent
      inhibition of conditioning taste aversion, the effect of excitotoxic lesions of
      the hippocampus, a region related to spatial-contextual modulation in this
      learning process, was analyzed. The latent inhibition of conditioning taste
      aversion in animals with hippocampal lesions, that were pre-exposed and
      conditioned to the same or different time of day, was compared with the response
      of animals exposed to either conditions ("same" or "different") but had undergone
      amygdala lesions or sham lesions. The results showed that selective dorsal
      hippocampus lesion eliminated the circadian dependence of latent inhibition of
      taste aversion. A change in the time of day between pre-exposure and conditioning
      did not prevent latent inhibition in animals with hippocampal lesions. In
      contrast, this change prevented latent inhibition in the amygdala-lesioned and
      sham groups. These findings suggest that the hippocampus contains a selective
      mechanism that modulates the contextual dependency of the latent inhibition of
      conditioning taste aversion without interfering with the effect of taste pre
      exposure itself. This study may help to understand the possible common
      involvement of the hippocampus in different types of contextual control of
      associative learning. 

PMID- 23973607
TI  - Astrocytic phosphorylation of PDK1 on Tyr9 following an excitotoxic lesion in the
      mouse hippocampus.
AB  - 3-phosphoinositide-dependent kinase-1 (PDK1) is suggested to play important roles
      in the regulation of synaptic plasticity and neuronal cell survival in the mature
      CNS. Although few studies have investigated the roles of PDK1, little is known
      about PDK1 changes in glial cells under neuropathological conditions. In current
      report, phosphorylation of PDK1 was monitored specially on tyrosine residues,
      following the induction of an excitotoxic lesion in rat brain by using kainic
      acid administration. In injured hippocampal CA3 region, Tyr9 phosphorylation of
      PDK1 was increased from 4h until 3 day post-injection. Double
      immunohistochemistry further evaluated that these phosphorylated forms of PDK1
      were localized in astrocytes not other cells. Overexpression of
      unphosphorylatable mutant, PDK1-Y9F leads to inhibit Protein kinase B (PKB/Akt)
      activation and cAMP responsive element binding protein (CREB) phosphorylation. In
      conclusion, our results suggested for the first time that tyrosine
      phosphorylation of PDK1 is required for PKB and CREB activation in KA-mediated
      excitotoxic lesion in mouse brain. 

PMID- 23973608
TI  - Hypoxia-induced plasticity in the metabolic response of a widespread cichlid.
AB  - The African cichlid, Pseudocrenilabrus multicolor victoriae is a eurytopic fish
      that exhibits high levels of developmental plasticity in response to dissolved
      oxygen availability. In this study, F1 offspring from three sites in the Mpanga
      River drainage of Western Uganda characterized by different dissolved oxygen
      (D.O.) regimes were reared under normoxic or hypoxic conditions. After 1 year,
      enzymes were measured to determine the tissue metabolic capacity of four
      different tissues: muscle, heart, brain and liver. The enzymes measured were
      pyruvate kinase [PK], lactate dehydrogenase [LDH], citrate synthase [CS], and
      cytochrome C oxidase [CCO], and an additional two, malate dehydrogenase (MDH) and
      fructose 1,6-bisphosphatase (FBPase), were examined in the liver only.
      Individuals reared under hypoxia exhibited elevated levels of LDH and CCO in the
      heart; and depressed activity levels of brain CS and liver CCO and MDH relative
      to normoxia-reared sibs. Results from this study demonstrate that long-term
      exposure to hypoxia during development can induce changes in the metabolic
      capacities of P. multicolor. This flexibility may be important in facilitating
      persistence in variable and/or novel environments, and in the face of increasing
      global hypoxia.

PMID- 23973609
TI  - Effects of phase stability and processing on the mechanical properties of Ti-Nb
      based beta Ti alloys.
AB  - The influence of beta phase stability on mechanical properties, deformation
      behaviours and phase composition were investigated for a series of Ti-24Nb-3Zr
      2Sn-xMo alloys in response to hot and cold rolling. For the hot rolled alloys,
      the phase composition and deformation behaviours were largely consistent with
      those predicted on the basis of a Bo-Md plot and the Ms estimates. The
      deformation mechanisms involve growth and/or reorientation of plate-like
      martensite and/or twins. However, these are largely restricted in the cold rolled
      alloys due to the effects of grain refinement and residual stress. The cold
      rolled alloys exhibit the highest strengthening in combination with more limited
      ductility, which increased with increasing beta phase stability. The moderately
      stable alloy, B, with e/a around 4.18 and Moeq~10wt% gave the greatest
      strengthening in response to cold rolling, which was related to intense localised
      grain refinement. 

PMID- 23973610
TI  - The impact of discrete compartments of a multi-compartment collagen-GAG scaffold
      on overall construct biophysical properties.
AB  - Orthopedic interfaces such as the tendon-bone junction (TBJ) present unique
      challenges for biomaterials development. Here we describe a multi-compartment
      collagen-GAG scaffold fabricated via lyophilization that contains discrete
      mineralized (CGCaP) and non-mineralized (CG) regions joined by a continuous
      interface. Modifying CGCaP preparation approaches, we demonstrated scaffold
      variants of increasing mineral content (40 vs. 80wt% CaP). We report the impact
      of fabrication parameters on microstructure, composition, elastic modulus, and
      permeability of the entire multi-compartment scaffold as well as discrete
      mineralized and non-mineralized compartments. Notably, individual mineralized and
      non-mineralized compartments differentially impacted the global properties of the
      multi-compartment composite. Of particular interest for the development of
      mechanically-loaded multi-compartment composites, the elastic modulus and
      permeability of the entire construct were governed primarily by the non
      mineralized and mineralized compartments, respectively. Based on these results we
      hypothesize spatial variations in scaffold structural, compositional, and
      mechanical properties may be an important design parameter in orthopedic
      interface repair. 

PMID- 23973611
TI  - Cohesive zone modeling of mode I tearing in thin soft materials.
AB  - The use of modeling and simulation is growing rapidly in applications such as
      surgery simulations, injury mechanics and tissue engineering. The aim of this
      study is to model and simulate tissue tearing and the resulting failure for use
      in such applications. In particular, our goal is to characterize the mechanics of
      mode I tearing in thin soft materials. We use the cohesive zone modeling approach
      to characterize the propagation of tears in a processed meat product (PMP). The
      bulk response of the PMP is modeled with a hyperelastic material model and the
      interface with a cohesive zone model. A multistep parameter estimation approach
      is developed to determine the bulk and the cohesive model parameters from
      uniaxial extension and tearing experiments. Results show that the proposed
      approach is able to capture both material and geometrical nonlinearities inherent
      to such problems, and accurately model the overall force-displacement response of
      thin soft materials during tearing at slow rates. 

PMID- 23973612
TI  - Functional buckling behavior of silicone rubber shells for biomedical use.
AB  - BACKGROUND: The use of soft elastic biomaterials in medical devices enables
      substantial function integration. The consequent increased simplification in
      design can improve reliability at a lower cost in comparison to traditional
      (hard) biomaterials. Functional bi-stable buckling is one of the many new
      mechanisms made possible by soft materials. The buckling behavior of shells,
      however, is typically described from a structural failure point of view: the
      collapse of arches or rupture of steam vessels, for example. There is little or
      no literature about the functional elastic buckling of small-sized silicone
      rubber shells, and it is unknown whether or not theory can predict their
      behavior. Is functional buckling possible within the scale, material and pressure
      normally associated with physiological applications? An automatic speech valve is
      used as an example application. METHOD OF APPROACH: Silicone rubber spherical
      shells (diameter 30mm) with hinged and double-hinged boundaries were subjected to
      air pressure loading. Twelve different geometrical configurations were tested for
      buckling and reverse buckling pressures. Data were compared with the theory.
      RESULTS: Buckling pressure increases linearly with shell thickness and shell
      height. Reverse buckling shows these same relations, with pressures always below
      normal buckling pressure. Secondary hinges change normal/reverse buckling
      pressure ratios and promote symmetrical buckling. All tested configurations
      buckled within or closely around physiological pressures. CONCLUSIONS: Functional
      bi-stable buckling of silicone rubber shells is possible with adjustable
      properties in the physiological pressure range. Results can be predicted using
      the proposed relations and equations.

PMID- 23973613
TI  - Fatigue prediction in fibrin poly-epsilon-caprolactone macroporous scaffolds.
AB  - Tissue engineering applications rely on scaffolds that during its service life,
      either for in-vivo or in vitro applications, are under loading. The variation of
      the mechanical condition of the scaffold is strongly relevant for cell culture
      and has scarcely been addressed. The fatigue life cycle of poly-epsilon
      caprolactone, PCL, scaffolds with and without fibrin as filler of the pore
      structure were characterized both dry and immersed in liquid water. It is
      observed that the there is a strong increase from 100 to 500 in the number of
      loading cycles before collapse in the samples tested in immersed conditions due
      to the more uniform stress distributions within the samples, the fibrin loading
      playing a minor role in the mechanical performance of the scaffolds. 

PMID- 23973614
TI  - Investigating a continuous shear strain function for depth-dependent properties
      of native and tissue engineering cartilage using pixel-size data.
AB  - A previously developed novel imaging technique for determining the depth
      dependent properties of cartilage in simple shear is implemented. Shear
      displacement is determined from images of deformed lines photobleached on a
      sample, and shear strain is obtained from the derivative of the displacement. We
      investigated the feasibility of an alternative systematic approach to numerical
      differentiation for computing the shear strain that is based on fitting a
      continuous function to the shear displacement. Three models for a continuous
      shear displacement function are evaluated: polynomials, cubic splines, and non
      parametric locally weighted scatter plot curves. Four independent approaches are
      then applied to identify the best-fit model and the accuracy of the first
      derivative. One approach is based on the Akaiki Information Criteria, and the
      Bayesian Information Criteria. The second is based on a method developed to
      smooth and differentiate digitized data from human motion. The third method is
      based on photobleaching a predefined circular area with a specific radius.
      Finally, we integrate the shear strain and compare it with the total shear
      deflection of the sample measured experimentally. Results show that 6th and 7th
      order polynomials are the best models for the shear displacement and its first
      derivative. In addition, failure of tissue-engineered cartilage, consistent with
      previous results, demonstrates the qualitative value of this imaging approach. 

PMID- 23973615
TI  - Mechanical characterization of brain tissue in simple shear at dynamic strain
      rates.
AB  - During severe impact conditions, brain tissue experiences a rapid and complex
      deformation, which can be seen as a mixture of compression, tension and shear.
      Diffuse axonal injury (DAI) occurs in animals and humans when both the strains
      and strain rates exceed 10% and 10/s, respectively. Knowing the mechanical
      properties of brain tissue in shear at these strains and strain rates is thus of
      particular importance, as they can be used in finite element simulations to
      predict the occurrence of brain injuries under different impact conditions.
      However, very few studies in the literature provide this information. In this
      research, an experimental setup was developed to perform simple shear tests on
      porcine brain tissue at strain rates <=120/s. The maximum measured shear stress
      at strain rates of 30, 60, 90 and 120/s was 1.15+/-0.25kPa, 1.34+/-0.19kPa,
      2.19+/-0.225kPa and 2.52+/-0.27kPa, (mean+/-SD), respectively at the maximum
      amount of shear, K=1. Good agreement of experimental, theoretical (Ogden and
      Mooney-Rivlin models) and numerical shear stresses was achieved (p=0.7866
      0.9935). Specimen thickness effects (2.0-10.0mm thick specimens) were also
      analyzed numerically and we found that there is no significant difference
      (p=0.9954) in the shear stress magnitudes, indicating a homogeneous deformation
      of the specimens during simple shear tests. Stress relaxation tests in simple
      shear were also conducted at different strain magnitudes (10-60% strain) with the
      average rise time of 14ms. This allowed us to estimate elastic and viscoelastic
      parameters (initial shear modulus, MU=4942.0Pa, and Prony parameters: g1=0.520,
      g2=0.3057, tau1=0.0264s, and tau2=0.011s) that can be used in FE software to
      analyze the non-linear viscoelastic behavior of brain tissue. This study provides
      new insight into the behavior in finite shear of brain tissue under dynamic
      impact conditions, which will assist in developing effective brain injury
      criteria and adopting efficient countermeasures against traumatic brain injury. 

PMID- 23973616
TI  - Effects of storage temperature on the mechanical properties of porcine kidney
      estimated using shear wave elastography.
AB  - The objective of this study was to evaluate the effects of different conservation
      techniques on the mechanical properties of the ex vivo porcine kidney in order to
      select an appropriate conservation protocol to use prior to mechanical testing.
      Five groups of eight kidneys each were subjected to different methods of
      conservation: storage at 4 degrees C, -18 degrees C, -34 degrees C and -71
      degrees C, for 7 days, or storage at 20 degrees C for 2 days only (as the tissues
      degraded quickly). Their shear modulus as a function of depth in the organ was
      evaluated before (fresh) and after conservation using shear wave elastography.
      Results obtained on fresh kidneys were collected within 6h of death. Freezing
      lead to a significant decrease (p<0.05) of the shear modulus in the most
      superficial zone (renal cortex), irrespectively of the freezing temperature (-18
      degrees C, -34 degrees C, -71 degrees C). There were no significant change
      (p>0.05) in the properties of the renal cortex when stored at 4 degrees C or 20
      degrees C. The average moduli in the central region of the kidney (medulla) were
      much higher than in the cortex and exhibited also exhibited larger specimen to
      specimen variations. The effects of the conservation method on the central region
      were not significant. Overall, the results suggest that kidney tissues should not
      be frozen prior to biomechanical characterization and that inhomogeneity may be
      important to consider for in biomechanical models. 

PMID- 23973617
TI  - Transfluthrin indoor air concentration and inhalation exposure during application
      of electric vaporizers.
AB  - Different household insecticide applications via two electric vaporizers emitting
      transfluthrin were realized in a full-scale experimental room under controlled
      air exchange rate conditions. On-line high-time resolved measurements of the gas
      phase concentrations of the active substance during and immediately after the
      spreading periods were performed with a High Sensitivity Proton-Transfer-Reaction
      Mass Spectrometer (HS-PTR-MS). Experimental and modelled data from the ConsExpo
      4.0 software were also compared to evaluate the sources of differences. Different
      application scenarios were also compared. Averaged inhaled concentrations over
      1h, 1week, and 5months were estimated to be 8.3, 1.8, and 1.8MUg.m(-3),
      respectively. Corresponding margins of exposures range from 1000 to 10,000,
      claiming for the absence of effect. Dermal and dust ingestion pathways, although
      roughly estimated, seems being non-negligible. This claims for a more in-depth
      integrated risk assessment. 

PMID- 23973618
TI  - Determining the relative importance of soil sample locations to predict risk of
      child lead exposure.
AB  - Soil lead in urban neighborhoods is a known predictor of child blood lead levels.
      In this paper, we address the question where one ought to concentrate soil sample
      collection efforts to efficiently predict children at-risk for soil Pb exposure.
      Two extensive data sets are combined, including 5467 surface soil samples
      collected from 286 census tracts, and geo-referenced blood Pb data for 55,551
      children in metropolitan New Orleans, USA. Random intercept least squares, random
      intercept logistic, and quantile regression results indicate that soils collected
      within 1m adjacent to residential streets most reliably predict child blood Pb
      outcomes in child blood Pb levels. Regression decomposition results show that
      residential street soils account for 39.7% of between-neighborhood explained
      variation, followed by busy street soils (21.97%), open space soils (20.25%), and
      home foundation soils (18.71%). Just as the age of housing stock is used as a
      statistical shortcut for child risk of exposure to lead-based paint, our results
      indicate that one can shortcut the characterization of child risk of exposure to
      neighborhood soil Pb by concentrating sampling efforts within 1m and adjacent to
      residential and busy streets, while significantly reducing the total costs of
      collection and analysis. This efficiency gain can help advance proactive
      upstream, preventive methods of environmental Pb discovery. 

PMID- 23973619
TI  - Comparative uptake and translocation of pharmaceutical and personal care products
      (PPCPs) by common vegetables.
AB  - Reuse of treated wastewater to irrigate agricultural crops is increasing in many
      arid and semi-arid areas around the world. The presence of numerous
      pharmaceutical and personal care products (PPCPs) in treated wastewater and their
      potential transfer into food produce such as vegetables poses an unknown human
      health risk. The goal of this study was to identify PPCPs that have a
      comparatively high potential for plant uptake and translocation. A total of 20
      frequently-occurring PPCPs were compared for their accumulation into four staple
      vegetables (lettuce, spinach, cucumber, and pepper) grown in nutrient solutions
      containing PPCPs at 0.5 or 5MUgL(-1). Triclocarban, fluoxetine, triclosan, and
      diazepam were found at high levels in roots, while meprobamate, primidone,
      carbamazepine, dilantin, and diuron exhibited more active translocation from
      roots to leaves. Root uptake of neutral PPCPs was positively correlated with the
      pH adjusted log Kow(i.e., log Dow), and was likely driven by chemical adsorption
      onto the root surfaces. In contrast, translocation from roots to leaves was
      negatively related to log Dow, suggesting hydrophilicity-regulated transport via
      xylems. Compounds preferentially sorbed to roots should be further evaluated for
      their uptake in tuber vegetables (e.g., carrot, radish) under field conditions,
      while those easily translocated into leaves (e.g., carbamazepine, dilantin) merit
      focused consideration for leafy and other vegetables (e.g., lettuce, cucumber).
      However, estimation of dietary intake by humans suggested the implied risks from
      exposure to PPCPs via wastewater irrigation to be negligible. 

PMID- 23973621
TI  - Dendritic cells and other innate determinants of T helper cell polarisation.
AB  - Adaptive immunity plays a crucial role in natural host defence against pathogens
      and tumours, and is central to the long-term protective effect of vaccines. It is
      mediated by T and B cells that are activated through antigen-specific receptors.
      By contrast, innate immunity responds immediately to infection and damage, and is
      activated through binding of conserved pathogen or damage-associated molecules to
      pattern recognition receptors (PRRs) on dendritic cells (DCs) and other innate
      immunity cell types. Recent studies have demonstrated that the innate immune
      system also functions to direct the adaptive immune response, not only through
      antigen presentation but also by providing the key signals for the
      differentiation of naive CD4+ T cells into functionally distinct T helper (Th)
      cell subtypes.

PMID- 23973620
TI  - Acute up-regulation of the rat brain somatostatin receptor-effector system by
      leptin is related to activation of insulin signaling and may counteract central
      leptin actions.
AB  - Leptin and somatostatin (SRIF) have opposite effects on food seeking and
      ingestive behaviors, functions partially regulated by the frontoparietal cortex
      and hippocampus. Although it is known that the acute suppression of food intake
      mediated by leptin decreases with time, the counter-regulatory mechanisms remain
      unclear. Our aims were to analyze the effect of acute central leptin infusion on
      the SRIF receptor-effector system in these areas and the implication of related
      intracellular signaling mechanisms in this response. We studied 20 adult male
      Wister rats including controls and those treated intracerebroventricularly with a
      single dose of 5 MUg of leptin and sacrificed 1 or 6h later. Density of SRIF
      receptors was unchanged at 1h, whereas leptin increased the density of SRIF
      receptors at 6h, which was correlated with an elevated capacity of SRIF to
      inhibit forskolin-stimulated adenylyl cyclase activity in both areas. The
      functional capacity of SRIF receptors was unaltered as cell membrane levels of
      alphai1 and alphai2 subunits of G inhibitory proteins were unaffected in both
      brain areas. The increased density of SRIF receptors was due to enhanced SRIF
      receptor subtype 2 (sst2) protein levels that correlated with higher mRNA levels
      for this receptor. These changes in sst2 mRNA levels were concomitant with
      increased activation of the insulin signaling, c-Jun and cyclic AMP response
      element-binding protein (CREB); however, activation of signal transducer and
      activator of transcription 3 was reduced in the cortex and unchanged in the
      hippocampus and suppressor of cytokine signaling 3 remained unchanged in these
      areas. In addition, the leptin antagonist L39A/D40A/F41A blocked the leptin
      induced changes in SRIF receptors, leptin signaling and CREB activation. In
      conclusion, increased activation of insulin signaling after leptin infusion is
      related to acute up-regulation of the SRIF receptor-effector system that may
      antagonize short-term leptin actions in the rat brain.

PMID- 23973623
TI  - Hotspots identification and ranking for road safety improvement: an alternative
      approach.
AB  - During the last decade, the concept of composite performance index, brought from
      economic and business statistics, has become a popular practice in the field of
      road safety, namely for the identification and classification of worst performing
      areas or time slots also known as hotspots. The overall quality of a composite
      index depends upon the complexity of phenomena of interest as well as the
      relevance of the methodological approach used to aggregate the various indicators
      into a single composite index. However, current aggregation methods used to
      estimate the composite road safety performance index suffer from various
      deficiencies at both the theoretical and operational level; these include the
      correlation and compensability between indicators, the weighting of the
      indicators as well as their high "degree of freedom" which enables one to readily
      manipulate them to produce desired outcomes (Munda and Nardo, 2003, 2005, 2009).
      The objective of this study is to contribute to the ongoing research effort on
      the estimation of road safety composite index for hotspots' identification and
      ranking. The aggregation method for constructing the composite road safety
      performance index introduced in this paper, strives to minimize the
      aforementioned deficiencies of the current approaches. Furthermore, this new
      method can be viewed as an intelligent decision support system for road safety
      performance evaluation, in order to prioritize interventions for road safety
      improvement. 

PMID- 23973622
TI  - Prostaglandin D2 toxicity in primary neurons is mediated through its bioactive
      cyclopentenone metabolites.
AB  - Prostaglandin D2 (PGD2) is the most abundant prostaglandin in brain but its
      effect on neuronal cell death is complex and not completely understood. PGD2 may
      modulate neuronal cell death via activation of DP receptors or its metabolism to
      the cyclopentenone prostaglandins (CyPGs) PGJ2, Delta(12)-PGJ2 and 15-deoxy
      Delta(12,14)-PGJ2, inducing cell death independently of prostaglandin receptors.
      This study aims to elucidate the effect of PGD2 on neuronal cell death and its
      underlying mechanisms. PGD2 dose-dependently induced cell death in rat primary
      neuron-enriched cultures in concentrations of >=10MUM, and this effect was not
      reversed by treatment with either DP1 or DP2 receptor antagonists. Antioxidants N
      acetylcysteine (NAC) and glutathione which contain sulfhydryl groups that can
      bind to CyPGs, but not ascorbate or tocopherol, attenuated PGD2-induced cell
      death. Conversion of PGD2 to CyPGs was detected in neuronal culture medium;
      treatment with these CyPG metabolites alone exhibited effects similar to those of
      PGD2, including apoptotic neuronal cell death and accumulation of ubiquitinated
      proteins. Disruption of lipocalin-type prostaglandin D synthase (L-PGDS)
      protected neurons against hypoxia. These results support the hypothesis that PGD2
      elicits its cytotoxic effects through its bioactive CyPG metabolites rather than
      DP receptor activation in primary neuronal culture. 

PMID- 23973624
TI  - The effect of pH and nitrite concentration on the antimicrobial impact of celery
      juice concentrate compared with conventional sodium nitrite on Listeria
      monocytogenes.
AB  - The objectives of this study were to evaluate the impact of pH and nitrite from
      celery juice concentrate (CJ) on the growth of Listeria monocytogenes in broth
      and on ham slices, and to evaluate the impact of pH and nitrite from CJ on
      quality attributes of the ham. The pH of both broth and ham were increased by the
      addition of CJ. The CJ was less effective than conventional nitrite at 100 mg/kg
      nitrite in broth, but in ham, the CJ treatments at both 100 and 200 mg/kg
      resulted in growth of L. monocytogenes (p>0.05) similar to that of the
      conventional nitrite at the same concentrations. Reducing the pH of CJ before
      addition to the ham had greater impact on L. monocytogenes growth at 200 mg/kg
      nitrite than at 100 mg/kg. Celery juice concentrate may increase meat product pH
      which could have implications for the antimicrobial impact of nitrite in some
      products.

PMID- 23973625
TI  - Temperature- and pH-dependent effect of lactate on in vitro redox stability of
      red meat myoglobins.
AB  - Our objective was to evaluate the influence of lactate on in vitro redox
      stability and thermostability of beef, horse, pork, and sheep myoglobins. Lactate
      (200 mM) had no effect (P>0.05) on redox stability at physiological (pH7.4, 37
      degrees C) and meat (pH 5.6, 4 degrees C) conditions. However, lactate increased
      (P<0.05) metmyoglobin formation at a condition simulating stressed live skeletal
      muscle (pH 6.5, 37 degrees C). The redox stability of myoglobins at stressed live
      skeletal muscle and meat conditions was species-specific (P<0.05). Myoglobin
      thermostability at 71 degrees C was lower (P<0.05) in the presence of lactate
      compared with controls and was influenced (P<0.05) by species. The results of the
      present study indicate that the effects of lactate on myoglobin are temperature
      and pH dependent. The observed lack of influence of lactate on myoglobin redox
      stability at meat condition suggests that the color stability of lactate-enhanced
      fresh meat is not due to direct interactions between the ingredient and the heme
      protein.

PMID- 23973626
TI  - Limited humoral and cellular responses to Q fever vaccination in older adults
      with risk factors for chronic Q fever.
AB  - OBJECTIVES: In the Netherlands, people at risk for chronic Q fever were
      vaccinated against Coxiella burnetii with the inactivated whole cell vaccine Q
      vax(r). We aimed to measure the immune responses to C. burnetii six and twelve
      months after vaccination in this relevant population. METHODS: In 260 vaccinees,
      antibody responses were assessed by immunofluorescence assay (IFA), complement
      fixation test and ELISA. The cellular immune responses were assessed by measuring
      C. burnetii-specific interferon (IFN)-gamma production in blood. Serological
      results of 200 individuals with past Q fever were used for comparison. RESULTS:
      At six months, 46% of vaccinees showed low IFA antibody titres and 67% had a
      positive IFN-gamma assay; At twelve months, both were 60%. In contrast,
      individuals with a past Q fever were seropositive in 99.5% at six and twelve
      months, with relatively higher IFA titres. Interestingly, vaccinees with positive
      IFN-gamma assay pre-vaccination, showed a higher seroconversion rate than IFN
      gamma negative vaccinees: 74% vs. 41% (p < 0.001). CONCLUSIONS: The immune
      response after Q-vax(r) vaccination is lower and restricted to a smaller
      proportion than found after past Q fever and than previously described after
      vaccination, suggesting decreased vaccine immunogenicity in this high-risk
      population. A positive IFN-gamma assay before vaccination in seronegative
      vaccinees likely points to pre-existing immunity resulting in boosting by
      vaccination.

PMID- 23973627
TI  - A chemiluminescence method to detect malondialdehyde in plasma and urine.
AB  - A highly sensitive and convenient method to detect malondialdehyde (MDA) in
      specimens of plasma and urine was developed using high-performance liquid
      chromatography combining chemiluminescence detection. MDA was separated through a
      reverse-phase C18 column at a flow rate of 0.8 ml min(-1). It was then detected
      by a chemiluminescence detector. Variables that affected chemiluminescence
      reaction, including mobile phase, flow rate, chemiluminescence reagent,
      parameters of the photomultiplier tube, and temperature, were studied. This assay
      was linear from 0.50 to 50 MUmol L(-1), with limits of detection and
      quantification of 0.08 and 0.30 MUmol L(-1), respectively. The recoveries were in
      the range of 92.2 to 98.5%, and the intra- and interday reproducibilities were
      obtained with relative standard deviations of less than 4% and less than 6%,
      respectively. MDA in plasma and urine was stable for 12 h at 4 degrees C. MDA
      levels were 2.74, 3.19, and 3.20 MUmol L(-1) for plasma and 1.25, 2.04, and 1.58
      MUmol L(-1) for urine, respectively. The proposed method is simple, rapid, and
      sensitive with low cost. Taken together, this method can be suitable for
      detecting MDA in tissue and feed specimens.

PMID- 23973628
TI  - Establishment of a reporter system to monitor silencing status in induced
      pluripotent stem cell lines.
AB  - Induced pluripotent stem (iPS) cells have proven to be an effective technology in
      regenerative medicine; however, the low efficiency of reprogramming is a major
      obstacle to the successful generation of iPS cell lines. One of the most
      important characteristics of a high-quality iPS cell line is the inactivation of
      transgenes driven by a retrovirus-derived long terminal repeat promoter. In this
      study, we established a novel marker system containing three kinds of proteins:
      secreted-type luciferase (MetLuc), copepod Pontellina plumata green fluorescent
      protein (copGFP), and an antibiotic-resistant gene product (Neo(r)). The
      introduction of MetLuc-copGFP-Neo(r) in mouse embryonic fibroblasts (MEFs)
      allowed us to monitor the reporter expression changes as an indicator of the
      state of silencing during reprogramming. Transformation of iPS cells induced a
      remarkable reduction in reporter activity, indicating that the retroviral
      silencing was detected successfully. Our system enables us to monitor the
      silencing status of transgenes and to efficiently select iPS cell lines that can
      be used for further applications.

PMID- 23973630
TI  - Analysis of 21-hydroxy deflazacort in human plasma by UPLC-MS/MS: application to
      a bioequivalence study in healthy volunteers.
AB  - A sensitive and rapid ultra performance liquid chromatography-tandem mass
      spectrometric (UPLC-MS/MS) method has been developed for the determination of 21
      hydroxy deflazacort in human plasma using betamethasone as the internal standard
      (IS). After solid-phase extraction from 100 MUL human plasma, the analyte and IS
      were analyzed on Waters Acquity UPLC BEH C18 (50 mm * 2.1 mm, 1.7 MUm) column
      using acetonitrile-4.0mM ammonium formate, pH 3.5 (90:10, v/v) as the mobile
      phase. The protonated analyte was quantified by selected reaction monitoring in
      the positive ionization mode by triple quadrupole mass spectrometer. The
      calibration plots were linear over the concentration range 0.50-500 ng/mL. Intra
      batch and inter-batch precision (% CV) and accuracy (%) for five quality control
      samples ranged within 1.40-4.82% and 98.0-102.0% respectively. The overall mean
      extraction recovery of 21-hydroxy deflazacort from plasma ranged from 95.3 to
      97.3%. Matrix effect was assessed by post-column analyte infusion and the
      extraction recovery was >95.0% across four quality control levels for the analyte
      and IS. Stability was evaluated under different conditions like bench top,
      autosampler, processed sample (at room temperature and in cooling chamber),
      freeze-thaw and long term stability. The method was applied to support a
      bioequivalence study of 30 mg deflazacort tablet formulation in 28 healthy
      subjects. Assay reproducibility was demonstrated by reanalysis of 115 incurred
      samples.

PMID- 23973629
TI  - A direct and continuous assay for the determination of thioredoxin reductase
      activity in cell lysates.
AB  - Thioredoxin reductase (TR) is an oxidoreductase responsible for maintaining
      thioredoxin in the reduced state, thereby contributing to proper cellular redox
      homeostasis. The C-terminal active site of mammalian TR contains the rare amino
      acid selenocysteine, which is essential to its activity. Alterations in TR
      activity due to changes in cellular redox homeostasis are found in clinical
      conditions such as cancer, viral infection, and various inflammatory processes;
      therefore, quantification of thioredoxin activity can be a valuable indicator of
      clinical conditions. Here we describe a new direct assay, termed the SC-TR assay,
      to determine the activity of TR based on the reduction of selenocystine, a
      diselenide-bridged amino acid. Rather than being an end-point assay as in older
      methods, the SC-TR assay directly monitors the continuous consumption of NADPH at
      340 nm by TR as it reduces selenocystine. The SC-TR assay can be used in a
      cuvette using traditional spectrophotometry or as a 96-well plate-based format
      using a plate reader. In addition, the SC-TR assay is compatible with the use of
      nonionic detergents, making it more versatile than other methods using cell
      lysates.

PMID- 23973631
TI  - Validated LC-MS/MS method for the determination of 3-hydroxflavone and its
      glucuronide in blood and bioequivalent buffers: application to pharmacokinetic,
      absorption, and metabolism studies.
AB  - The purpose of this study is to develop an UPLC-MS/MS method to quantify 3
      hydroxyflavone (3-HF) and its metabolite, 3-hydroxyflavone-glucuronide (3-HFG)
      from biological samples. A Waters BEH C8 column was used with acetonitrile/0.1%
      formic acid in water as mobile phases. The mass analysis was performed in an API
      5500 Qtrap mass spectrometer via multiple reaction monitoring (MRM) with positive
      scan mood. The one-step protein precipitation by acetonitrile was used to extract
      the analytes from blood. The results showed that the linear response range was
      0.61-2500.00 nM for 3-HF and 0.31-2500.00 nM for 3-HFG. The intra-day variance is
      less than 16.5% and accuracy is in 77.7-90.6% for 3-HF and variance less than
      15.9%, accuracy in 85.1-114.7% for 3-HFG. The inter-day variance is less than
      20.2%, accuracy is in 110.6-114.2% for 3-HF and variance less than 15.6%,
      accuracy in 83.0-89.4% for 3-HFG. The analysis was done within 4.0 min. Only 10
      MUl of blood is needed due to the high sensitivity of this method. The validated
      method was successfully used to pharmacokinetic study in A/J mouse, transport
      study in the Caco-2 cell culture model, and glucuronidation study using mice
      liver and intestine microsomes. The applications revealed that this method can be
      used for 3-HF and 3-HFG analysis in blood as well as in bioequivalent buffers
      such HBSS and KPI.

PMID- 23973632
TI  - LC-MS/MS-based quantification of clinically relevant intestinal uptake and efflux
      transporter proteins.
AB  - Multidrug transporter proteins are crucial determinants in the pharmacokinetics
      of many drugs. To evaluate their impact on intestinal drug absorption, we
      developed and validated quantification methods for 10 uptake transporters
      (OATP1A2, OATP2B1, PEPT1, ASBT, OCT1, OCT3) and efflux transporters (ABCB1,
      ABCC2, ABCC3, ABCG2) that have been reported to be expressed and to be of
      clinical relevance in the human intestine. Quantification was performed by
      targeted liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based
      quantification of proteospecific peptides after tryptic digestion using stable
      isotope labeled internal standard peptides. The chromatography of the respective
      peptides was performed by gradient elution using a reversed phase (C18) column
      (Kinetex((r)), 100 * 3.0 mm, 2.6 MUm) and 0.1% formic acid (FA) and acetonitrile
      with 0.1% FA as mobile phases at a flow rate of 0.5 ml/min. The MS/MS detection
      was done in the positive multiple reaction monitoring (MRM) mode by monitoring in
      each case three mass transitions for the transporter-derived peptides and the
      internal standard peptides. The assays were validated with respect to
      specificity, linearity (0.1-25 nM), within-day and between-day accuracy and
      precision as well as stability according to current bioanalytical guidelines.
      Finally, the developed methods were used to determine the transporter protein
      content in human intestinal tissue (jejunum and ileum). The methods were shown to
      possess sufficient specificity, sensitivity, accuracy, precision and stability to
      measure transporter proteins in the human intestine.

PMID- 23973633
TI  - Spectroscopic investigation of tolmetin interaction with human serum albumin.
AB  - The interaction of tolmetin (TOL) with human serum albumin (HSA) in physiological
      buffer solution (pH 7.4) was studied by fluorescence and UV-vis absorption
      spectroscopy at different temperatures, combined with time-resolved fluorescence
      measurements. The experimental results showed that there was a strong
      fluorescence quenching of HSA by tolmetin. Using the continuous variation method,
      a single class of binding sites for TOL on HSA was put in evidence. The binding
      constants Ka were calculated at different temperatures, using a nonlinear fit to
      the experimental data, and the thermodynamic parameters DeltaH(0), DeltaS(0) and
      DeltaG(0) were given. The obtained thermodynamic signature suggests that at least
      van der Waals and electrostatic type interactions are present. Quenching
      efficiency calculations, based on steady state and time-resolved spectroscopy,
      indicate that both static and dynamic quenching mechanisms are present. 

PMID- 23973634
TI  - Determination of salmeterol in dried blood spot using an ionic liquid based
      dispersive liquid-liquid microextraction coupled with HPLC.
AB  - A novel analytical method based on the use of a modified dispersive liquid-liquid
      microextraction (DLLME) technique by ionic liquids has been developed for the
      first time. This method was applied for the determination of salmeterol in dried
      blood spot samples from asthmatic patients followed by HPLC system equipped with
      fluorescence detector. The main novelty of the present work deals with the
      analysis of salmeterol in dried blood spot with significant advantages with
      regard to invasive sampling, volume of blood used (<20 MUL), storage and
      transport of biological materials and requirements for special biohazard
      arrangements. The effects of significant factors in microextraction procedure
      including extracting and disperser solvents volume, sample pH and salt contents
      were investigated. Under optimized conditions, the mean recoveries were higher
      than 90.0% with linear responses about 1.00-500 ng mL(-1) concentration range.
      The limit of detection (LOD) was 0.30 ng mL(-1) in S/N of 3. Intra-day (n=6) and
      inter-day (n=3) assay precision showed relative standard deviation lower than 6.0
      and 8.5% for studied drug, respectively. The developed microextraction procedure
      was simpler and faster than conventional extraction techniques and was omitted
      hazard organic solvents. Finally, the proposed method is suitable for the
      analysis of salmeterol in dried blood spots from asthmatic patients for
      therapeutic drug monitoring purpose.

PMID- 23973635
TI  - Resting-state functional connectivity in multiple sclerosis: an examination of
      group differences and individual differences.
AB  - Multiple sclerosis (MS) is a neurodegenerative, inflammatory disease of the
      central nervous system, resulting in physical and cognitive disturbances. The
      goal of the current study was to examine the association between network
      integrity and composite measures of cognition and disease severity in individuals
      with relapsing-remitting MS (RRMS), relative to healthy controls. All
      participants underwent a neuropsychological and neuroimaging session, where
      resting-state data was collected. Independent component analysis and dual
      regression were employed to examine network integrity in individuals with MS,
      relative to healthy controls. The MS sample exhibited less connectivity in the
      motor and visual networks, relative to healthy controls, after controlling for
      group differences in gray matter volume. However, no alterations were observed in
      the frontoparietal, executive control, or default-mode networks, despite previous
      evidence of altered neuronal patterns during tasks of exogenous processing. Whole
      brain, voxel-wise regression analyses with disease severity and processing speed
      composites were also performed to elucidate the brain-behavior relationship with
      neuronal network integrity. Individuals with higher levels of disease severity
      demonstrated reduced intra-network connectivity of the motor network, and the
      executive control network, while higher disease burden was associated with
      greater inter-network connectivity between the medial visual network and areas
      involved in visuomotor learning. Our findings underscore the importance of
      examining resting-state oscillations in this population, both as a biomarker of
      disease progression and a potential target for therapeutic intervention. 

PMID- 23973636
TI  - Effect of American ginseng (Panax quinquefolius L.) on arterial stiffness in
      subjects with type-2 diabetes and concomitant hypertension.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Substantial pre-clinical and some clinical data
      are available showing that Asian ginseng (Panax ginseng C.A. Meyer) varieties or
      its particular ginsenosides exert a vasodilatating effect, thus may modulate
      vascular function. However, the clinical evidence for American ginseng (Panax
      quinquefolius L.) is scarce. Therefore, this study evaluates the effect of
      American ginseng (AG) on arterial stiffness, as measured by augmentation index
      (AI), and blood pressure (BP), in type 2 diabetes patients with concomitant
      hypertension. MATERIALS AND METHODS: Using a double-blind, placebo-controlled,
      parallel design, each participant was randomized to either the selected AG
      extract or placebo at daily dose of 3g for 12 weeks as an adjunct to their usual
      antihypertensive and anti-diabetic therapy (diet and/or medications). AI and BP
      were measured by applanation tonometry at baseline and after 12 weeks of
      treatment. RESULTS: A total of 64 individuals with well-controlled essential
      hypertension and type 2 diabetes (gender: 22 M:42 F, age:63 +/- 9.3 years, BP:
      145 +/- 10.8/84 +/- 8.0 mmHg, HbA1c: 7.0 +/- 1.3%, fasting blood glucose (FBG):
      8.1 +/- 2.3 mmol/L) completed the study. Compared to placebo, 3g of AG
      significantly lowered radial AI by 5.3% (P=0.041) and systolic BP by 11.7%
      (P<0.001) at 12 weeks. No effect was observed with diastolic BP. CONCLUSIONS:
      Addition of AG extract to conventional therapy in diabetes with concomitant
      hypertension improved arterial stiffness and attenuated systolic BP, thus
      warrants further investigation on long-term endothelial parameters before
      recommended as an adjunct treatment.

PMID- 23973637
TI  - Comparative analysis of ER stress response into HIV protease inhibitors:
      lopinavir but not darunavir induces potent ER stress response via ROS/JNK
      pathway.
AB  - HIV protease inhibitor (PI)-induced ER stress has been associated with adverse
      effects. Although it is a serious clinical problem for HIV/AIDS patients,
      comparative analyses of ER stress induction by clinically used PIs have rarely
      been done. Especially, there is no report on the differential ER stress response
      between lopinavir (LPV) and darunavir (DRV), although these PIs are the most
      clinically used PIs. We show here that LPV induces the most potent CHOP
      expression, ER stress marker, among the 9 Food and Drug Administration (FDA)
      approved PIs in human peripheral blood mononuclear cells, several human
      epithelial cells, and mouse embryonic fibroblasts. LPV induced the most potent
      ROS production and JNK activation in 9 PIs. A comparison among the most
      clinically used PIs, ritonavir (RTV), LPV, and DRV, revealed that LPV potently
      and RTV moderately but not DRV induced ER stress via ROS-dependent JNK activation
      rather than proteasome inhibition. Finally, we analyzed ER stress induction in
      tissues of mice intraperitoneally injected with RTV, LPV, and DRV. RTV and LPV
      but not DRV showed ER stress induction in several mice tissues. In conclusion, we
      first identify LPV as the most potent ER stress inducing PI among 9 FDA-approved
      PIs in human cells, and although clinical verification is necessary, we show here
      that DRV has the advantage of less ROS and ER stress induction potential compared
      with LPV in vitro and in vivo. 

PMID- 23973638
TI  - Signaling properties of 4-hydroxyalkenals formed by lipid peroxidation in
      diabetes.
AB  - Peroxidation of polyunsaturated fatty acids is intensified in cells subjected to
      oxidative stress and results in the generation of various bioactive compounds, of
      which 4-hydroxyalkenals are prominent. During the progression of type 2 diabetes
      mellitus, the ensuing hyperglycemia promotes the generation of reactive oxygen
      species (ROS) that contribute to the development of diabetic complications. It
      has been suggested that ROS-induced lipid peroxidation and the resulting 4
      hydroxyalkenals markedly contribute to the development and progression of these
      pathologies. Recent findings, however, also suggest that noncytotoxic levels of 4
      hydroxyalkenals play important signaling functions in the early phase of diabetes
      and act as hormetic factors to induce adaptive and protective responses in cells,
      enabling them to function in the hyperglycemic milieu. Our studies and others'
      have proposed such regulatory functions for 4-hydroxynonenal and 4
      hydroxydodecadienal in insulin secreting beta-cells and vascular endothelial
      cells, respectively. This review presents and discusses the mechanisms regulating
      the generation of 4-hydroxyalkenals under high glucose conditions and the
      molecular interactions underlying the reciprocal transition from hormetic to
      cytotoxic agents. 

PMID- 23973639
TI  - Adjunctive use of verapamil in patients with refractory temporal lobe epilepsy: a
      pilot study.
AB  - OBJECTIVE: The present study aimed to determine if adjunctive use of verapamil,
      as a P-glycoprotein (P-gp) inhibitor, is efficacious in decreasing seizure
      frequency in patients with refractory temporal lobe epilepsy. MATERIALS AND
      METHODS: This was an open-label pilot study. Adult patients with refractory
      temporal lobe epilepsy were studied. Baseline seizure type and seizure count were
      determined. Patients were divided randomly into two groups. Group A received
      verapamil 120 mg/day (n=13), and group B received 240 mg/day (n=6). All patients
      were followed for eight weeks. The proportion of responders, which consist of
      patients with more than 50% reduction in seizure frequency from baseline, was
      tabulated. RESULTS: Nineteen patients were studied. Seven patients (36.84%)
      reached the responder rate. Three patients (50%) in group B were among the
      responders; two of these patients achieved seizure freedom. Four patients (30.7%)
      in group A responded favorably to verapamil. CONCLUSION: Developing new means of
      improving the effectiveness of existing antiepileptic drugs is a desirable way of
      tackling the dilemma of medically refractory epilepsy. Hypothetically, P-gp
      inhibitors (e.g., verapamil) might be used to counteract the removal of AEDs from
      the epileptogenic tissue. Such a strategy was adopted in this non-placebo
      controlled, open-label, pilot study. We observed a significant achievement in
      seizure control associated with adjunctive use of verapamil in patients with
      refractory temporal lobe epilepsy.

PMID- 23973640
TI  - Transition and transfer from pediatric to adult health care in epilepsy: a
      families' survey on Dravet syndrome.
AB  - We used a questionnaire to ascertain the perception of transition and transfer
      from pediatric to adult health-care system in patients with Dravet syndrome and
      their families. Sixty families received the questionnaire. We had a response rate
      of 85%. Sixty-one percent of patients experienced a transfer. Factors that
      positively impacted transfer were the quality of transition preparation
      (p<.000001), a longer duration of follow-up by the same child neurologist
      (p<.001), the availability of the child neurology staff (p<.01), a transfer into
      the adult health-care system after the age of 18 (p<.01), and a stable medical
      condition before transfer (p<.05). All families reported a positive experience in
      the pediatric health-care system. Child neurologists were considered as
      welcoming, available, and helpful. Their experience in the adult health-care
      system was similar to pediatric care. Almost all patients who experienced
      "transfer" reported no gap in this process. 

PMID- 23973641
TI  - Determinants of intelligence in childhood-onset epilepsy: a single-center study.
AB  - The purpose of this study was to quantify the intelligence of children with
      epilepsy and to determine the clinical factors associated with intellectual
      impairment. The medical records of patients diagnosed with childhood-onset
      epilepsy at a single tertiary medical center in Korea between 2006 and 2011 were
      retrospectively reviewed. The Korean Education Development Institute-Wechsler
      Intelligence Scale for Children or Korean Wechsler Intelligence Scale for adults
      was used to quantify the level of intelligence. Age at seizure onset, etiology,
      epilepsy duration, number of seizures in the last year, use of antiepileptic
      drugs, EEG/MRI findings, and epilepsy classification were recorded. The
      association between clinical factors and the intelligence was determined using
      logistic regression. Three hundred and twenty-two patients were included in the
      analysis. One hundred and seventy-six (54.7%) patients had low intelligence
      (intelligence quotient [IQ]<80) with 18 (5.6%) defined as borderline mental
      retardation (IQ 70-79), 47 (14.6%) as mild mental retardation (IQ 60-69), and 111
      (34.5%) as moderate-to-severe mental retardation (IQ<60). Epilepsy duration,
      number of seizures in the last year, and epilepsy classification were
      significantly associated with low intelligence in multivariate logistic
      regression (p<0.05). However, when analyzed according to etiology, these factors
      were not associated with low intelligence in children with idiopathic epilepsy.
      The most important factors associated with low intelligence in childhood-onset
      epilepsy are the underlying etiology and, in cryptogenic and symptomatic
      epilepsy, seizure burden. The results of this study underscore the importance of
      seizure control to alleviate the harmful impact of epilepsy on cognition. 

PMID- 23973642
TI  - Aphasic seizures in patients with temporopolar and anterior temporobasal lesions:
      a video-EEG study.
AB  - Studies of patients with temporal lobe epilepsy provide few descriptions of
      seizures that arise in the temporopolar and the anterior temporobasal brain
      region. Based on connectivity, it might be assumed that the semiology of these
      seizures is similar to that of medial temporal lobe epilepsy. However,
      accumulating evidence suggests that the anterior temporobasal cortex may play an
      important role in the language system, which could account for particular
      features of seizures arising here. We studied the electroclinical features of
      seizures in patients with circumscribed temporopolar and temporobasal lesions in
      order to identify specific features that might differentiate them from seizures
      that originate in other temporal areas. Among 172 patients with temporal lobe
      seizures registered in our epilepsy unit in the last 15 years, 15 (8.7%) patients
      had seizures caused by temporopolar or anterior temporobasal lesions (11 left
      sided lesions). The main finding in our study is that patients with left-sided
      lesions had aphasia during their seizures as the most prominent feature. In
      addition, while all patients showed normal to high intellectual functioning in
      standard neuropsychological testing, semantic impairment was found in a subset of
      9 patients with left-sided lesions. This case series demonstrates that aphasic
      seizures without impairment of consciousness can result from small, circumscribed
      left anterior temporobasal and temporopolar lesions. Thus, the presence of speech
      manifestation during seizures should prompt detailed assessment of the structural
      integrity of the basal surface of the temporal lobe in addition to the evaluation
      of primary language areas.

PMID- 23973643
TI  - Emotional dysregulation, alexithymia, and attachment in psychogenic nonepileptic
      seizures.
AB  - OBJECTIVES: Psychogenic nonepileptic seizures (PNESs) are poorly understood and
      difficult to treat. Research and theory suggest that problems with recognizing,
      acknowledging, and regulating emotional states (i.e., emotional dysregulation)
      may contribute to the development and maintenance of PNESs. However, there is a
      lack of well-controlled studies using dedicated measures of emotional regulation
      with patients with PNESs. The current study sought to address this gap. METHODS:
      Forty-three patients with PNESs and 24 with epilepsy completed a postal survey
      comprising measures of emotional dysregulation (Difficulties in Emotion
      Regulation Scale), alexithymia (Toronto Alexithymia Scale), attachment
      (Relationship Scales Questionnaire), and psychopathology (Generalized Anxiety
      Disorder-7; Patient Health Questionnaire-9; Somatoform Dissociation Questionnaire
      20). Cluster analysis was used to identify possible subgroups of patients with
      PNESs characterized by distinct patterns of emotional dysregulation. RESULTS: Two
      clusters of patients with PNESs were identified. The first (n=11) was
      characterized by higher levels of psychopathology, somatization, alexithymia, and
      difficulties with most aspects of emotional regulation (including identifying,
      accepting, and describing feelings, accessing adaptive regulatory strategies,
      performing goal-directed behaviors, and controlling feelings and actions)
      compared with the group with epilepsy. The second (n=32) was characterized by
      relatively high somatization and depression scores but comparatively normal
      levels of alexithymia and emotional regulation. CONCLUSIONS: The findings suggest
      that patients with PNESs can be divided into at least two meaningful subgroups
      characterized by distinct psychological profiles, only one of which is
      characterized by significant problems with emotional dysregulation. Further
      research is needed to determine whether the relatively normal emotional
      dysregulation and high somatization scores of some patients with PNESs are due to
      emotional avoidance or more basic problems with perceptual and behavioral
      control.

PMID- 23973644
TI  - Cost-effectiveness analysis of antiepileptic drugs in the treatment of Lennox
      Gastaut syndrome.
AB  - An economic model evaluated the costs and outcomes of adjunctive clobazam therapy
      for Lennox-Gastaut syndrome (LGS) compared with adjunctive lamotrigine,
      rufinamide, and topiramate. Clinical data were used to estimate baseline
      frequency and the percentage of drop-seizure reductions over 3 months (all
      comparators) and 2 years (rufinamide). Claims data from a large US health care
      plan were employed to estimate costs. After 3 months, 21.5% of those receiving
      clobazam were drop-seizure-free. Over a 3-month horizon, clobazam was more
      effective and less expensive than comparators, with the assumption that >0.77% of
      drop seizures required medical care. Below this threshold, topiramate was less
      costly than clobazam. With the base-case assumption that 2.3% of drop seizures
      were medically attended, costs for patients receiving clobazam totaled $30,147
      versus $34,223-$35,378 for comparators. Clobazam was more efficacious and less
      costly than rufinamide over a 2-year horizon. The percentage of medically
      attended drop seizures was a driver of results. Clobazam treatment may be cost
      saving.

PMID- 23973646
TI  - Olanzapine induces glucose intolerance through the activation of AMPK in the
      mouse hypothalamus.
AB  - Treatment with atypical antipsychotic drugs is known to increase the risk of
      glucose intolerance and diabetes. However, the mechanism of this effect is
      unclear. Since central adenosine 5'-monophosphate-activated protein kinase (AMPK)
      plays an important role in regulating nutrient homeostasis, the present study was
      performed to examine the involvement of central AMPK in the glucose intolerance
      induced by olanzapine, an atypical antipsychotic drug, in mice. Acute
      intraperitoneal treatment with olanzapine dose-dependently increased blood
      glucose levels in the glucose tolerance test. Intracerebroventricular
      administration of olanzapine also increased blood glucose levels in the glucose
      tolerance test. The glucose intolerance induced by both intraperitoneal and
      intracerebroventricular treatment with olanzapine was significantly attenuated by
      intracerebroventricular pretreatment with the AMPK inhibitor compound C.
      Intracerebroventricular treatment with the AMPK activator AICAR increased blood
      glucose levels in the glucose tolerance test, and this increase was inhibited by
      compound C. Moreover, the hypothalamic level of phosphorylated AMPK after glucose
      injection was significantly increased by intracerebroventricular pretreatment
      with olanzapine. Olanzapine did not affect plasma glucagon and insulin levels.
      Our results indicate that acute treatment with olanzapine causes glucose
      intolerance through the activation of hypothalamic AMPK. The present study
      suggests that the inhibition of central AMPK activity may have a therapeutic
      effect on the metabolic disturbance induced by atypical antipsychotic drugs. 

PMID- 23973645
TI  - Maturation-dependent behavioral deficits and cell injury in developing animals
      during the subacute postictal period.
AB  - Prolonged early-life seizures are associated with disruptions of affective and
      cognitive function. Postictal disturbances, temporary functional deficits that
      persist for hours to days after seizures, have not yet been thoroughly
      characterized. Here, we used kainic acid (KA) to induce status epilepticus (SE)
      in immature rats at three developmental stages (postnatal day (P) 15, 21, or 30)
      and subsequently assessed spatial learning and memory in a Barnes maze,
      exploratory behavior in an open field, and the spatiotemporal distribution of
      cell injury during the first 7-10 days of the postictal period. At 1 day post-SE,
      P15-SE rats showed no deficit in the Barnes maze but were hyperexploratory in an
      open field compared with their littermate controls. In contrast, P21- and P30-SE
      rats exhibited markedly impaired performance in the Barnes maze and exhibited
      significantly reduced open field exploration suggestive of anxiety-like behavior.
      These behavioral changes were transient in P15 rats but more persistent in P21
      and enduring in P30 rats after KA-SE. The time course of behavioral deficits in
      P21 and P30 rats was temporally correlated with the presence of neuronal injury
      in the lateral septal nuclei, amygdala, and ventral subiculum/CA1, regions
      involved in modulation of the hypothalamic-pituitary-adrenal stress response.

PMID- 23973647
TI  - Mechanisms underlying the antinociceptive effect of mangiferin in the formalin
      test.
AB  - The purpose of this study was to investigate the possible antinociceptive effect
      of mangiferin, a glucosylxanthone present in Mangifera indica L., in inflammatory
      pain. Furthermore, we sought to investigate the possible mechanisms action that
      contributes to these effects. The ipsilateral local peripheral (1-30 ug/paw),
      intrathecal (1-30 ug/rat) and oral (1-30 mg/kg) administration of mangiferin
      produced a dose-dependent reduction in formalin-induced nociception. The
      antinociceptive effect of this drug was similar to that induced by diclofenac
      after oral and local peripheral administration. Furthermore, mangiferin was also
      able to reduce 0.1% capsaicin- and serotonin-induced nociceptive behavior. The
      local peripheral antinociceptive effect of mangiferin in the formalin test was
      blocked by naloxone (50 MUg/paw), naltrindole (1 MUg/paw), 5-guanidinonaltrindole
      (5-GNTI, 1 MUg/paw), N(G)-L-nitro-arginine methyl ester (L-NAME, 100 ug/paw), 1H
      (1,2,4)-oxadiazolo [4,2-a]quinoxalin-1-one (ODQ, 50 ug/paw) and glibenclamide (50
      MUg/paw), but not by methiothepin (30 MUg/paw). These results suggest that the
      antinociceptive effects induced by mangiferin are mediated by the peripheral
      opioidergic system involving the activation of delta, kappa, and probably u,
      receptors, but not serotonergic receptors. Data also suggests that mangiferin
      activates the NO-cyclic GMP-ATP-sensitive K(+) channels pathway in order to
      produce its local peripheral antinociceptive effect in the formalin test.
      Mangiferin may prove to be effective in treating inflammatory pain in humans.

PMID- 23973648
TI  - Willem Hendrik Gispen--an interview.
AB  - This text is based on three long interviews in Utrecht University's Faculty Club,
      and on almost 40 years of working together in the same city, the same department,
      the same university. 

PMID- 23973649
TI  - Correction of vascular hypercontractility in spontaneously hypertensive rats
      using shRNAs-induced delta protein kinase C gene silencing.
AB  - Potassium conductance in vascular smooth muscle (VSM) is known to be altered in
      arterial hypertension. High level of protein kinase C (PKC) activity is a common
      feature for hypertension of different genesis. The main goal of this study was to
      investigate the efficacy of the RNA interference (RNAi) technique targeting PKC
      delta-isoform gene as a possible pharmacological tool to restore vasodilator
      potential in spontaneously hypertensive rats (SHR). Experimental design of the
      study comprised RNAi and patch-clamp techniques, RT-PCR analysis and standard
      acetylcholine test. Total outward currents and acetylcholine-induced endothelium
      dependent relaxant responses were blunted in SHR. BKCa alpha subunit mRNA
      expression in SHR was unchanged whereas KV and KATP mRNA expression appeared
      significantly increased. PKC inhibitor, chelerythrine (100 nM), restored
      potassium channels activity in SHR. PKC-delta-isoform protein expression and PKC
      delta-isoform mRNA expression are 2.5-4 fold increased in VSM from SHR. PKC gene
      silencing with the short hairpin RNAs (shRNAs)-plasmid delivery system
      administered intravenously led to an increment in maximal amplitude of
      acetylcholine-relaxation, restored outward K(+) currents and PKC-delta-isoform
      mRNA and protein expression. Arterial blood pressure in SHR was normalized
      following shRNAs administration. We conclude that BKCa channels are likely to be
      the most PKC-dependent member of K(+) channels family responsible for vascular
      hypercontractility in SHR while Kv and KATP channels may constitute a reserve
      mechanism for the maintenance of vasodilator potential under BKCa channelopathy.
      It is likely that RNAi technique is a good therapeutic approach to inactivate PKC
      gene and to normalize vascular functions and high arterial blood pressure in SHR.

PMID- 23973650
TI  - Induction of cyclooxygenase-2 expression by prostaglandin E2 stimulation of the
      prostanoid EP4 receptor via coupling to Galphai and transactivation of the
      epidermal growth factor receptor in HCA-7 human colon cancer cells.
AB  - Increased expressions of cyclooxygenase-2 (COX-2) and its downstream metabolite,
      prostaglandin E2 (PGE2), are well documented events in the development of
      colorectal cancer. Interestingly, PGE2 itself can induce the expression of COX-2
      thereby creating the potential for positive feedback. Although evidence for such
      a positive feedback has been previously described, the specific E-type prostanoid
      (EP) receptor subtype that mediates this response, as well as the relevant
      signaling pathways, remain unclear. We now report that the PGE2 stimulated
      induction of COX-2 expression in human colon cancer HCA-7 cells is mediated by
      activation of the prostanoid EP4 receptor subtype and is followed by coupling of
      the receptor to Galphai and the activation of phosphatidylinositol 3-kinase.
      Subsequent activation of metalloproteinases releases membrane bound heparin
      binding epidermal growth factor-like growth factor resulting in the
      transactivation of epidermal growth factor receptors and the activation of the
      extracellular signal-regulated kinases and induction of COX-2 expression. This
      induction of COX-2 expression by PGE2 stimulation of the prostanoid EP4 receptor
      may underlie the upregulation of COX-2 during colorectal cancer and appears to be
      an early event in the process of tumorigenesis. 

PMID- 23973651
TI  - Strategies of Echinococcus species responses to immune attacks: implications for
      therapeutic tool development.
AB  - Echinococcus species have been studied as a model to investigate parasite-host
      interactions. Echinococcus spp. can actively communicate dynamically with a host
      to facilitate infection, growth and proliferation partially via secretion of
      molecules, especially in terms of harmonization of host immune attacks. This
      review systematically outlines our current knowledge of how the Echinococcus
      species have evolved to adapt to their host's microenvironment. This
      understanding of parasite-host interplay has implications in profound
      appreciation of parasite plasticity and is informative in designing novel and
      effective tools including vaccines and drugs for the treatment of echinococcosis
      and other diseases. 

PMID- 23973652
TI  - Relaxin attenuates silica-induced pulmonary fibrosis by regulating collagen type
      I and MMP-2.
AB  - Silicosis is one of the most prevalent occupational lung diseases, but the
      pathogenic mechanisms of silicosis are largely unknown and an effective treatment
      is not yet available. In this study, we investigated the potential effects of
      relaxin (RLX) on fibrosis by an in vitro model involving silica-induced and
      macrophage-mediated pulmonary fibroblasts. Following pre-treatment with DQ12
      quartz, the culture supernatant of human monocytic THP-1 cells was added to human
      fetal lung fibroblast MRC-5 cells with or without RLX. DQ12 significantly induced
      an increase of TGFB1 mRNA in THP-1 cells, coinciding with elevated TGF-beta1
      protein excretion in the supernatant, but RLX had no effect on DQ12-stimulated
      TGF-beta1 secretion in THP-1 cells. Furthermore, RLX inhibited the proliferation
      of MRC-5 cells, and reduced the mRNA level and protein secretion of collagen type
      I, whereas it increased the mRNA level and protein activity of MMP-2 in MRC-5
      cells treated with THP-1 cell culture supernatant. Our data suggest that RLX may
      inhibit TGF-beta1-mediated fibrosis during the process of silicosis, providing
      evidence for the protective effect of RLX on silica-induced pulmonary fibrosis. 

PMID- 23973653
TI  - Proton pump inhibitor selectively suppresses proliferation and restores the
      chemosensitivity of gastric cancer cells by inhibiting STAT3 signaling pathway.
AB  - BACKGROUNDS AND AIMS: Recent studies reported that pretreatment of proton pump
      inhibitors (PPIs) induced sensitization to chemotherapeutic agents in several
      cancer cells. The devastating effects of PPIs on tumor cells were discovered and
      raised great interests; therefore we designed the following experiments to fully
      explain the direct antitumor effects of PPIs. METHODS: We compared the viability
      of gastric cancer cells and epithelia cells in buffered and unbuffered culture
      conditions with PPZ treatment by WST-8 assay. The sensitivity to cisplatin of
      gastric cancer cells with/without PPZ pretreatment was assessed by IC50
      calculation and Annexin V/PI assay. The secretion of IL-6 was detected by ELISA.
      Western blot analysis and real time RT-PCR were used to evaluate the expression
      and activation of STAT3 and its downstream targets. RESULTS: PPZ selectively
      exhibited a dose-dependent cytotoxic effect of gastric cancer cells in acidic
      unbuffered medium. Low dose of PPZ pretreatment (20 MUg/mL) enhanced the
      sensitivity to cisplatin in gastric cancer cells. PPZ induced cell apoptosis and
      reduced the secretion of the pro-inflammatory cytokine IL-6 specifically in
      gastric cancer cells, but had no effect on the epithelia cells. Consequently, the
      activation of STAT3, not the total amount, was suppressed by PPZ in gastric
      cancer cells. The downstream targets of STAT3, c-Myc, cyclin D1 and Bcl-2 were
      also down-regulated. CONCLUSION: PPZ causes gastric cancer cell death by
      induction of apoptosis and its mechanism of action is mediated in part via the
      inhibition of IL-6/STAT3 pathway.

PMID- 23973654
TI  - Antithrombotic activities of pellitorine in vitro and in vivo.
AB  - Pellitorine (PLT), an active amide compound, is well known to possess
      insecticidal, antibacterial and anticancer properties. However, the anti
      coagulant functions of PLT are not studied yet. Here, the anticoagulant
      activities of PLT were examined by monitoring activated partial thromboplastin
      time (aPTT), prothrombin time (PT), and the activities of cell-based thrombin and
      activated factor X (FXa). Furthermore, the effects of PLT on the expressions of
      plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen
      activator (t-PA) were tested in tumor necrosis factor (TNF)-alpha activated human
      umbilical vein endothelial cells (HUVECs). Treatment with PLT resulted in
      prolonged aPTT and PT and inhibition of the activities of thrombin and FXa, and
      PLT inhibited production of thrombin and FXa in HUVECs. And PLT inhibited
      thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance
      with these anticoagulant activities, PLT elicited anticoagulant effects in mouse.
      In addition, treatment with PLT resulted in the inhibition of TNF-alpha-induced
      production of PAI-1 and in the significant reduction of the PAI-1 to t-PA ratio.
      Collectively, PLT possesses antithrombotic activities and offers bases for
      development of a novel anticoagulant. 

PMID- 23973655
TI  - Anti-inflammatory ligustilides from Ligusticum chuanxiong Hort.
AB  - Four new ligustilides chuanxiongnolide R1 (1), chuanxiongnolide R2 (2),
      chuanxiongdiolide R1 (3) and chuanxiongdiolide R2 (4) together with eight known
      derivatives (5-12) were isolated from the root of Ligusticum chuanxiong Hort.
      Their structures were elucidated by HR-ESI-MS, UV, IR, 1D and 2D NMR (HSQC, HMBC,
      (1)H-(1)H COSY, NOESY) methods. The absolute configurations were confirmed via
      the circular dichroism (CD) spectrum. The anti-inflammatory assay in LPS
      triggered RAW 264.7 macrophages was carried out on the twelve compounds. 1, 3, 5
      and 6 showed significant inhibitory effects against LPS-induced NO production. 

PMID- 23973656
TI  - Metabolic engineering of Ralstonia eutropha for the biosynthesis of 2-hydroxyacid
      containing polyhydroxyalkanoates.
AB  - Polyhydroxyalkanoates (PHAs) are bio-based and biodegradable polyesters
      synthesized by numerous microorganisms. PHAs containing 2-hydroxyacids as monomer
      units have attracted much attention, but their production has not been efficient.
      Here, we metabolically engineered Ralstonia eutropha strains for the in vivo
      synthesis of PHAs containing 2-hydroxyacids as monomers. This was accomplished by
      replacing the R. eutropha phaC gene in the chromosome with either the R. eutropha
      phaC S506G A510K gene, which contains two point mutations, or the Pseudomonas sp.
      MBEL 6-19 phaC1437 gene. In addition, the R. eutropha phaAB genes in the
      chromosome were replaced with the Clostridium propionicum pct540 gene. All of the
      engineered R. eutropha strains produced PHAs containing 2-hydroxyacid monomers,
      including lactate and 2-hydroxybutyrate (2HB), along with 3-hydroxybutyrate (3HB)
      and/or 3-hydroxyvalerate (3HV), when they were cultured in nitrogen-free medium
      containing 5 g/L lactate or 4 g/L 2HB and 20 g/L glucose as carbon sources.
      Expression of the Escherichia coli ldhA gene in engineered R. eutropha strains
      allowed production of poly(3-hydroxybutyrate-co-lactate) [P(3HB-co-LA)] from
      glucose as the sole carbon source. This is the first report on the production of
      2-hydroxyacid-containing PHAs by metabolically engineered R. eutropha.

PMID- 23973657
TI  - Evaluation of the potential role of a new mutation in mabA in modifying the
      response of Mycobacterium tuberculosis to isoniazid.
AB  - A new mutation in mabA, Thr4Ile, was identified in a Mycobacterium tuberculosis
      isolate from a patient whose culture remained positive after treatment. The same
      mutation was found in another 5 patients infected by different strains. A
      putative role for this mutation in the process of diminishing susceptibility to
      isoniazid is evaluated. 

PMID- 23973658
TI  - Synthesis and acetylcholinesterase inhibitory activity of polyhydroxylated
      sulfated steroids: structure/activity studies.
AB  - Disulfated and trisulfated steroids have been synthesized from cholesterol and
      their acetylcholinesterase inhibitory activity has been evaluated. In our studies
      we have found that the activity was not only dependent on the location of the
      sulfate groups but on their configurations. 2beta,3alpha,6alpha-trihydroxy-5alpha
      cholestan-6-one trisulfate (18) was the most active steroid with an IC50 value of
      15.48 MUM comparable to that of 2beta,3alpha-dihydroxy-5alpha-cholestan-6-one
      disulfate (1). Both compounds were found to be less active than the reference
      compound eserine. The butyrylcholinesterase activity of 1 and 18 was one
      magnitude lower than that against acetylcholinesterase revealing a selective
      inhibitor profile.

PMID- 23973659
TI  - Antibiotics for treatment and prevention of exacerbations of chronic obstructive
      pulmonary disease.
AB  - Acute exacerbations (AE) can be recurrent problems for patients with moderate-to
      severe chronic obstructive pulmonary disease (COPD) increasing morbidity and
      mortality. Evidence suggests that >=50% of acute exacerbations involve bacteria
      requiring treatment with an antibiotic which should have high activity against
      the causative pathogens. However, sputum analysis is not a pre-requisite for
      antibiotic prescription in outpatients as results are delayed and patients are
      likely to be colonised with bacteria in the stable state. Clinicians rely on the
      clinical symptoms, sputum appearance and the patient's medical history to decide
      if an AE-COPD should be treated with antibiotics. This article reviews the
      available data of antibiotic trials in AE-COPD. Management of frequent
      exacerbators is particularly challenging for physicians. This may include
      antibiotic prophylaxis, especially macrolides because of anti-inflammatory
      properties; though successful in reducing exacerbations, concerns about
      resistance development remain. Inhalation of antibiotics achieves high local
      concentrations and minimal systemic exposure; therefore, it may represent an
      attractive alternative for antibiotic prophylaxis in certain COPD patients.
      Inhaled antibiotic prophylaxis has been successfully used in other respiratory
      conditions such as non-cystic fibrosis bronchiectasis which itself might be
      present in COPD patients who have chronic bacterial infection, particularly with
      Pseudomonas aeruginosa. 

PMID- 23973660
TI  - Cost effectiveness of interferon-gamma release assay for TB screening of HIV
      positive pregnant women in low TB incidence countries.
AB  - OBJECTIVE: To assess the cost effectiveness for tuberculosis (TB) screening of
      high-risk human immunodeficiency virus (HIV) positive pregnant women by using
      interferon-gamma release assays (IGRAs) compared to the tuberculin skin test
      (TST) in low TB incidence countries. METHODS: We constructed Markov models using
      a public health payer perspective. The target population was a hypothetical
      cohort of 20 year-olds HIV positive pregnant women until age 50 years in three
      most common screening situations; close contacts, immigrants from high burden
      countries and occasional screenings. BCG vaccination status was considered. Five
      strategies; TST, QuantiFERON(r)-TB Gold In-Tube (QFT), T-SPOT(r). TB (T-SPOT),
      TST followed by QFT and TST followed by T-SPOT were modeled. The main outcome
      measure of effectiveness was quality-adjusted life-years (QALYs) gained. The
      incremental cost effectiveness ratio (ICER) of each screening arm was applied and
      compared. RESULTS: In the base case analyses of close contacts, T-SPOT yielded
      the greatest benefits at the lowest cost. In the base case analyses of immigrants
      and occasional screenings, TST followed by QFT yielded the greatest benefits at
      the lowest cost. CONCLUSIONS: Using an IGRA for TB screening of high-risk HIV
      positive pregnant women is recommended on the basis of the cost effectiveness in
      low TB incidence countries.

PMID- 23973661
TI  - Genetic and chemical characterization of an EMS induced mutation in Cucumis melo
      CRTISO gene.
AB  - In order to broaden the available genetic variation of melon, we developed an
      ethyl methanesulfonate mutation library in an orange-flesh 'Charentais' type
      melon line that accumulates beta-carotene. One mutagenized M2 family segregated
      for a novel recessive trait, a yellow-orange fruit flesh ('yofI'). HPLC analysis
      revealed that 'yofI' accumulates pro-lycopene (tetra-cis-lycopene) as its major
      fruit pigment. The altered carotenoid composition of 'yofI' is associated with a
      significant change of the fruit aroma since cleavage of beta-carotene yields
      different apocarotenoids than the cleavage of pro-lycopene. Normally, pro
      lycopene is further isomerized by CRTISO (carotenoid isomerase) to yield all
      trans-lycopene, which is further cyclized to beta-carotene in melon fruit.
      Cloning and sequencing of 'yofI' CRTISO identified two mRNA sequences which lead
      to truncated forms of CRTISO. Sequencing of the genomic CRTISO identified an A-T
      transversion in 'yofI' which leads to a premature STOP codon. The early
      carotenoid pathway genes were up regulated in yofI fruit causing accumulation of
      other intermediates such as phytoene and zeta-carotene. Total carotenoid levels
      are only slightly increased in the mutant. Mutants accumulating pro-lycopene have
      been reported in both tomato and watermelon fruits, however, this is the first
      report of a non-lycopene accumulating fruit showing this phenomenon.

PMID- 23973662
TI  - Dual role of IL-12 in the therapeutic efficacy or failure during combined PEG
      Interferon-alpha2A and ribavirin therapy in patients with chronic hepatitis C.
AB  - Several efforts have been made to establish novel biomarkers with relevant
      predictive values to monitor HCV-infected patients under pegilated Interferon
      alpha2A-(PEG-IFN-alpha2A)/ribavirin therapy. The aim of this study was to monitor
      the kinetics of HCV viral load, serum levels of pro-inflammatory/regulatory
      cytokines and leukocyte activation status before and after PEG-IFN
      alpha2A/ribavirin therapy in 52 volunteers, including 12 chronic HCV patients and
      40 controls. The HCV viral load, serum levels of cytokines (IL-8/IL-6/TNF
      alpha/IL-12/IFN-gamma/IL-4/IL-10) and the phenotype of peripheral blood
      leukocytes were evaluated before and after 4, 12 and 24 weeks following the PEG
      IFN-alpha2A/ribavirin therapy. Our results demonstrated that sustained
      virological response-(SVR) is associated with early decrease in the viral load
      after 4 weeks of treatment. The presence of a modulated pro-inflammatory profile
      at baseline favors SVR, whereas a strong inflammatory response at baseline
      predisposes to therapeutic failure. Furthermore, a time-dependent increase on
      serum IL-12 levels in patients under treatment is critical to support the SVR,
      while the early predominance of IL-10 correlates to late virological relapse. On
      the other hand, a broad but unguided "cytokine storm" is observed in the non
      responder HCV patients after 12 weeks of treatment. Corroborating these findings,
      monocyte/lymphocyte activation at baseline is associated with the non-responders
      to therapy whereas high CD8(+) T-cell numbers associate with SVR. All in all,
      these data suggest that the baseline pattern of serum pro-inflammatory/regulatory
      cytokines and the immunological activation status of chronic HCV patients
      undergoing PEG-IFN-alpha2A/ribavirin therapy are closely related with the
      therapeutic response. 

PMID- 23973664
TI  - The Orosomucoid 1 protein is involved in the vitamin D - mediated macrophage de
      activation process.
AB  - Orosomucoid 1 (ORM1), also named Alpha 1 acid glycoprotein A (AGP-A), is an
      abundant plasma protein characterized by anti-inflammatory and immune-modulating
      properties. The present study was designed to identify a possible correlation
      between ORM1 and Vitamin D3 (1,25(OH)2D3), a hormone exerting a widespread effect
      on cell proliferation, differentiation and regulation of the immune system. In
      particular, the data described here indicated that ORM1 is a 1,25(OH)2D3 primary
      response gene, characterized by the presence of a VDRE element inside the 1kb
      sequence of its proximal promoter region. This finding was demonstrated with gene
      expression studies, Chromatin Immunoprecipitation and luciferase transactivation
      experiments and confirmed by VDR full length and dominant negative over
      expression. In addition, several experiments carried out in human normal
      monocytes demonstrated that the 1,25(OH)2D3--VDR--ORM1 pathway plays a functional
      role inside the macrophage de-activation process and that ORM1 may be considered
      as a signaling molecule involved in the maintenance of tissue homeostasis and
      remodeling.

PMID- 23973665
TI  - Conditioned medium from alternatively activated macrophages induce mesangial cell
      apoptosis via the effect of Fas.
AB  - During inflammation in the glomerulus, the proliferation of myofiroblast-like
      mesangial cells is commonly associated with the pathological process. Macrophages
      play an important role in regulating the growth of resident mesangial cells in
      the glomeruli. Alternatively activated macrophage (M2 macrophage) is a subset of
      macrophages induced by IL-13/IL-4, which is shown to play a repair role in
      glomerulonephritis. Prompted by studies of development, we performed bone marrow
      derived macrophage and rat mesangial cell co-culture study. Conditioned medium
      from IL-4 primed M2 macrophages induced rat mesangial cell apoptosis. The pro
      apoptotic effect of M2 macrophages was demonstrated by condensed nuclei stained
      with Hoechst 33258, increased apoptosis rates by flow cytometry analysis and
      enhanced caspase-3 activation by western blot. Fas protein was up-regulated in
      rat mesangial cells, and its neutralizing antibody ZB4 partly inhibited M2
      macrophage-induced apoptosis. The up-regulated arginase-1 expression in M2
      macrophage also contributed to this apoptotic effect. These results indicated
      that the process of apoptosis triggered by conditioned medium from M2
      macrophages, at least is partly conducted through Fas in rat mesangial cells. Our
      findings provide compelling evidence that M2 macrophages control the growth of
      mesangial cells in renal inflammatory conditions. 

PMID- 23973666
TI  - GW9508, a free fatty acid receptor agonist, specifically induces cell death in
      bone resorbing precursor cells through increased oxidative stress from
      mitochondrial origin.
AB  - GW9508 is a free fatty acid receptor agonist able to protect from ovariectomy
      induced bone loss in vivo thought inhibition of osteoclast differentiation in a G
      coupled Protein Receptor 40 (GPR40)-dependent way. In this study, we questioned
      whether higher doses of GW9508 may also influence resorbing cell viability
      specifically. Interestingly, GW9508 at 100 uM altered osteoclast precursor (OcP)
      viability while it had positive effects on osteoblastic precursors suggesting an
      activity dependent on the cell lineage. According to 7-AAD/Annexin-V staining,
      induced OcP cell death was found to be associated with necrosis mechanisms.
      Consistently, GW9508 led to a sustained establishment of oxidative stress from
      mitochondrial origin. In contrast to previous observations on osteoclast
      differentiation inhibition, OcP viability targeted by high doses of GW9508
      appeared to be independent of GPR40 involvement. Although mediating structures
      remain to be determined, our data demonstrate for the first time that this fatty
      acid receptor agonist driving OcP specific cell death may now open new
      perspectives regarding therapeutic strategies in osteolytic disorders.

PMID- 23973667
TI  - Undifferentiated MSCs are able to myelinate DRG neuron processes through p75.
AB  - Over the last few years the therapeutic approach to demyelinating diseases has
      radically changed, strategies having been developed aimed at partnering the
      classic symptomatic treatments with the most advanced regenerative medicine
      tools. At first, the transplantation of myelinogenic cells, Schwann cells or
      oligodendrocytes was suggested, but the considerable technical difficulties,
      (poor availability, difficulties in harvesting and culturing, and the problem of
      rejection in the event of non-autologous sources), shifted attention towards more
      versatile cellular types, such as Mesenchymal Stem Cells (MSCs). Recent studies
      have already demonstrate both in vitro and in vivo that glially-primed MSCs
      (through exposure to chemical cocktails) have myelogenic abilities. In spite of a
      large number of papers on glially-differentiated MSCs, little is known about the
      ability of undifferentiated MSCs to myelinate axons and processes. Here we have
      demonstrated that also undifferentiated MSCs have the ability to myelinate, since
      they induce the myelination of rat DRG neuron processes after direct co
      culturing. In this process a pivotal role is performed by the p75 receptor. 

PMID- 23973668
TI  - Cell migration or cytokinesis and proliferation?--revisiting the "go or grow"
      hypothesis in cancer cells in vitro.
AB  - The mortality of patients with solid tumors is mostly due to metastasis that
      relies on the interplay between migration and proliferation. The "go or grow"
      hypothesis postulates that migration and proliferation spatiotemporally excludes
      each other. We evaluated this hypothesis on 35 cell lines (12 mesothelioma, 13
      melanoma and 10 lung cancer) on both the individual cell and population levels.
      Following three-day-long videomicroscopy, migration, proliferation and
      cytokinesis-length were quantified. We found a significantly higher migration in
      mesothelioma cells compared to melanoma and lung cancer while tumor types did not
      differ in mean proliferation or duration of cytokinesis. Strikingly, we found in
      melanoma and lung cancer a significant positive correlation between mean
      proliferation and migration. Furthermore, non-dividing melanoma and lung cancer
      cells displayed slower migration. In contrast, in mesothelioma there were no such
      correlations. Interestingly, negative correlation was found between cytokinesis
      length and migration in melanoma. FAK activation was higher in melanoma cells
      with high motility. We demonstrate that the cancer cells studied do not defer
      proliferation for migration. Of note, tumor cells from various organ systems may
      differently regulate migration and proliferation. Furthermore, our data is in
      line with the observation of pathologists that highly proliferative tumors are
      often highly invasive. 

PMID- 23973663
TI  - Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of
      carcinogenic hazard.
AB  - The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental
      pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by
      a Working Group of the International Agency for Research on Cancer (IARC).
      Information on exposures, relevant data from epidemiologic studies, bioassays in
      experimental animals, and toxicity and mechanism of action studies was used to
      conclude that TCE is carcinogenic to humans (Group 1). This article summarizes
      the key evidence forming the scientific bases for the IARC classification.
      Exposure to TCE from environmental sources (including hazardous waste sites and
      contaminated water) is common throughout the world. While workplace use of TCE
      has been declining, occupational exposures remain of concern, especially in
      developing countries. The strongest human evidence is from studies of
      occupational TCE exposure and kidney cancer. Positive, although less consistent,
      associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is
      carcinogenic at multiple sites in multiple species and strains of experimental
      animals. The mechanistic evidence includes extensive data on the toxicokinetics
      and genotoxicity of TCE and its metabolites. Together, available evidence
      provided a cohesive database supporting the human cancer hazard of TCE,
      particularly in the kidney. For other target sites of carcinogenicity,
      mechanistic and other data were found to be more limited. Important sources of
      susceptibility to TCE toxicity and carcinogenicity were also reviewed by the
      Working Group. In all, consideration of the multiple evidence streams presented
      herein informed the IARC conclusions regarding the carcinogenicity of TCE.

PMID- 23973670
TI  - Graphene oxide-based magnetic fluorescent hybrids for drug delivery and cellular
      imaging.
AB  - A graphene oxide (GO)-based multifunctional hybrid has been developed for loading
      and delivery of anticancer drugs. The GO was functionalized by
      magnetic/fluorescent SiO2 microsphere via an amidation process. Doxorubicin (DOX)
      was chosen as a model drug to be loaded onto the GO via pi-pi stacking and
      hydrophobic interaction. The loading capacities of DOX to the GO-based magnetic
      fluorescent hybrids were investigated. The release profiles of DOX from the
      hybrids were depicted. The fluorescence images of the GO-based magnetic
      fluorescent hybrids indicated that the hybrids would be an effective drug carrier
      and a potential optical imaging tool. The application of the developed GO-based
      magnetic fluorescent hybrids for HepG2 cells demonstrated an excellent
      therapeutic effect of the DOX loaded hybrids to the target tumor. 

PMID- 23973669
TI  - Snail/beta-catenin signaling protects breast cancer cells from hypoxia attack.
AB  - The tolerance of cancer cells to hypoxia depends on the combination of different
      factors--from increase of glycolysis (Warburg Effect) to activation of
      intracellular growth/apoptotic pathways. Less is known about the influence of
      epithelial-mesenchymal transition (EMT) and EMT-associated pathways on the cell
      sensitivity to hypoxia. The aim of this study was to explore the role of Snail
      signaling, one of the key EMT pathways, in the mediating of hypoxia response and
      regulation of cell sensitivity to hypoxia, using as a model in vitro cultured
      breast cancer cells. Earlier we have shown that estrogen-independent HBL-100
      breast cancer cells differ from estrogen-dependent MCF-7 cells with increased
      expression of Snail1, and demonstrated Snail1 involvement into formation of
      hormone-resistant phenotype. Because Snail1 belongs to hypoxia-activated
      proteins, here we studied the influence of Snail1 signaling on the cell tolerance
      to hypoxia. We found that Snail1-enriched HBL-100 cells were less sensitive to
      hypoxia-induced growth suppression if compared with MCF-7 line (31% MCF-7 vs. 71%
      HBL-100 cell viability after 1% O2 atmosphere for 3 days). Snail1 knock-down
      enhanced the hypoxia-induced inhibition of cell proliferation giving the direct
      evidence of Snail1 involvement into cell protection from hypoxia attack. The
      protective effect of Snail1 was shown to be mediated, at least in a part, via
      beta-catenin which positively regulated expression of HIF-1-dependent genes.
      Finally, we found that cell tolerance to hypoxia was accompanied with the failure
      in the phosphorylation of AMPK - the key energy sensor, and demonstrated an
      inverse relationship between AMPK and Snail/beta-catenin signaling. Totally, our
      data show that Snail1 and beta-catenin, besides association with loss of hormone
      dependence, protect cancer cells from hypoxia and may serve as an important
      target in the treatment of breast cancer. Moreover, we suggest that the level of
      these proteins as well the level of AMPK phosphorylation may be considered as
      predictors of the tumor sensitivity to anti-angiogenic drugs.

PMID- 23973671
TI  - PDMS bonding to a bio-friendly photoresist via self-polymerized poly(dopamine)
      adhesive for complex protein micropatterning inside microfluidic channels.
AB  - Protein micropatterned surfaces integrated with microfluidics are useful in
      numerous bioanalytical and biological applications. In this study, we
      demonstrated the fabrication of complex protein micropatterned surfaces within
      poly(dimethylsiloxane) (PDMS) microfluidic channels by attaching the PDMS
      channels to bio-friendly photoresist films and subsequently performing microscope
      projection photolithography (MPP). A muscle-inspired poly(dopamine) (PDA) coating
      was employed to mediate the bonding between the PDMS and the bio-friendly
      photoresist poly(2,2-dimethoxy nitrobenzyl methacrylate-r-methyl methacrylate-r
      poly(ethylene glycol) methacrylate) (PDMP). By adjusting the dip-coating time for
      the PDA coating, we could successfully introduce sufficient amounts of functional
      groups on the PDMP surfaces to mediate strong bonding between the PDMS channels
      and the PDA-coated PDMP thin films with minimal alteration of the surface
      properties of the PDMP thin films that are critical for protein micropatterning.
      Using this novel bonding strategy, we successfully fabricated multiple protein
      micropatterns and gradient micropatterns of proteins within microfluidic
      channels. The technique developed in this study will be useful for the
      fabrication of complex biochips for multiplex bioassays and fundamental cell
      biological studies. 

PMID- 23973672
TI  - Isocyanate-mediated covalent immobilization of Mucor miehei lipase onto SBA-15
      for transesterification reaction.
AB  - Mucor miehei lipase (Mm-L) covalently bind on a hexagonally ordered silica SBA-15
      (Santa Barbara Amorphous), previously functionalized with isocyanate moieties,
      was examined as biocatalyst for transesterification of colza oil with methanol.
      The isocyanate-mesoporous silica (NCO-SBA-15) was obtained by condensation of
      silanol with triethoxysilane propyl isocyanate (TPI). The efficiency of the
      functionalization has been evidenced by infrared, (29)Si and (13)C NMR
      spectroscopies. The substrate provided a moderate hydrophobic microenvironment
      together with reactive sites for chemical immobilization of the enzyme. The
      biocatalyst containing 0.28 g of Mm-L per gram of support afforded a high level
      of transesterification activity (yield up to 80%) while using 1:1 molar ratio of
      methanol/colza oil and small amount of water. The biocatalyst showed higher
      operational stability than the corresponding physisorbed enzyme since it can be
      reused 6 times against 2 consecutive runs for the physisorbed enzyme. 

PMID- 23973673
TI  - Amphiphilic activities of anionic sodium cholate (NaC), zwitterionic 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and their mixtures: a
      comparative study.
AB  - Anionic biological surfactant sodium cholate (NaC) and the zwitterionic nontoxic
      surfactant CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate)
      having common steroidal skeleton have not been studied in a comparative level to
      explore their amphiphilic behaviors separately and in mixed states. Their
      adsorption at the interface in relation to self-association in solution has been
      examined in both pure and mixed states with reference to detailed thermodynamic
      analysis of their surface chemical and solution behaviors. Their head group
      differences are responsible for the differences in their properties viz. critical
      micelle concentration (CMC), aggregation number (N), hydrodynamic diameter, Gibbs
      surface excess (Gammamax), minimum head group area (Amin), mixed micelle
      composition and their mixing ideality/nonideality. Although the CMC values found
      from tensiometry and isothermal titration calorimetry (ITC) are in good
      agreement, the standard enthalpy of micellization (DeltaHm(0)) found from ITC at
      different temperatures are different from that evaluated by the van't Hoff
      method. This is because van't Hoff rationale is a differential method which
      estimates the enthalpy of the monomer <-> micelle equilibrium process whereas
      calorimetry is an integral process that evaluates all probable/possible processes
      in addition to monomer to micelle conversion. Results are analyzed, compared and
      discussed in the light of physicochemical parameters of pure NaC and CHAPS and
      their mixtures. These fundamental findings are considered prospective in
      pharmaceutical, biochemical and biomedical applications of the studied bio
      friendly amphiphiles. 

PMID- 23973674
TI  - KfrA plasmid protein monolayers on latex particles-electrokinetic measurements.
AB  - Monolayers of KfrA, a protein assisting in bacteria plasmid segregation, on
      polystyrene latex particles were produced in controlled self-assembling under
      diffusion-controlled conditions. The coverage of the protein was quantitatively
      determined as a function of ionic strength (up to 0.15 M, NaCl) via micro
      electrophoretic measurements and concentration depletion with the aid of AFM
      imaging. The maximum monolayer coverage of KfrA  monotonically increased with
      ionic strength attaining 2.0 mg m(-2) for 0.15 M, NaCl that corresponds to the
      dimensionless coverage of 0.48. This is in accordance with theoretical
      calculations derived from the random sequential adsorption modeling assuming a
      tetrameric aggregation state. A high stability of the monolayers in pH cycling
      experiments was confirmed, which proves the irreversibility of protein adsorption
      on latex. The acid base properties and the electrokinetic charge of monolayers
      were also determined via the electrophoretic mobility measurements carried out
      for various ionic strength. In this way the isoelectric point of the protein of
      4.8 was determined, which is prohibitive via bulk measurements. It was concluded
      that the procedure used in our work is reliable and efficient for characterizing
      physicochemical properties if minor amounts of a protein are available. 

PMID- 23973675
TI  - Temperature dependence of the interaction of prazosin with lipid Langmuir
      monolayers.
AB  - The influence of temperature on membrane-prazosin interactions was studied.
      Prazosin, a quinazoline derivative of 2-furoylpiperazine, is a classic
      antihypertensive and antiarrhythmic drug. A mixed cholesterol/phospholipid
      monolayer at the water/air interface was employed as a simplified biomembrane
      model. Brewster angle microscopy (BAM) was used to visualize the monolayer
      morphology. It was found that prazosin penetrates Langmuir monolayers and
      modifies the interactions between membrane components, causing monolayer
      fluidization. An increase in temperature facilitates penetration of prazosin into
      the monolayers. Prazosin interacts preferentially with phosphatidylcholine and
      modifies the morphology of the condensed phase domains of DPPC. In the presence
      of prazosin, monolayers collapse at lower surface pressures. The difference
      between the collapse pressures of monolayers on water with and without prazosin
      increases with temperature. 

PMID- 23973676
TI  - Causes of gastrointestinal hemorrhage in patients with chronic renal failure.

PMID- 23973677
TI  - Sox9-dependent acinar-to-ductal reprogramming is critical for pancreatic
      intraepithelial neoplasia formation.

PMID- 23973678
TI  - New-generation treatment? Targeted antiviral therapy for rotavirus.

PMID- 23973679
TI  - Liver regeneration during acute-on-chronic liver failure using growth factors: in
      vivo or ex vivo indulgence of bone marrow?

PMID- 23973680
TI  - Death knell for placebo-controlled trials in chronic idiopathic constipation?

PMID- 23973681
TI  - Sequence-specific Ni(II)-dependent peptide bond hydrolysis for protein
      engineering: active sequence optimization.
AB  - In previous studies we showed that Ni(II) ions can hydrolytically cleave a
      peptide bond preceding Ser/Thr in peptides of a general sequence RN-(Ser/Thr)-Xaa
      His-Zaa-RC, where RN and RC are any peptide sequences. A peptide library
      screening, assisted by accurate measurements of reaction kinetics for selected
      peptides, demonstrated the preference for bulky and aromatic residues at variable
      positions Xaa and Zaa [A. Krezel, E. Kopera, A.M. Protas, A. Wyslouch-Cieszynska,
      J. Poznanski, W. Bal, J. Am. Chem. Soc., 132 (2010) 3355-3366]. In this work we
      used a similar strategy to find out whether the next residue downstream to Zaa
      may influence the reaction rate. Using an Ac-Gly-Ala-Ser-Arg-His-Zaa-Baa-Arg-Leu
      NH2 library, with Zaa and Baa positions containing all common amino acids except
      of Cys, we found a very strong preference for aromatic residues in both variable
      positions. This finding significantly limits the range of useful Xaa, Zaa and Baa
      substitutions, thus facilitating the search for optimal sequences for protein
      engineering applications [E. Kopera, A. Belczyk-Ciesielska, W. Bal, PLoS One 7
      (2012) e36350]. 

PMID- 23973682
TI  - Effects of chrysin, apigenin, genistein and their homoleptic copper(II) complexes
      on the growth and metastatic potential of cancer cells.
AB  - The (iso-)flavonoids chrysin 1, apigenin 2, genistein 3 and their homoleptic
      copper(II) complexes 4-6 were compared for general cancer cell growth inhibition
      and for antimetastatic effects on rapidly proliferating and metastasizing 518A2
      melanoma cells. The complexes 4-6 were three to five times more active than the
      free flavonoids in cytotoxicity assays with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide] against 518A2 melanoma, HCT-116 colon, KB-V1/Vbl
      cervix, and MCF-7/Topo breast carcinoma cells. This activity correlated with an
      arrest of the cell cycle of 518A2 melanoma cells at the G2/M transition. The
      complexes also diminished the migration propensity of these cells in wound
      healing assays more distinctly than the flavonoid ligands. By fluorescent
      staining of F-actin and beta-catenin the antimetastatic effects of the Cu(II)
      genistein complex 6 were shown to originate from a remodeling of the actin
      cytoskeleton and an increase in cadherin-catenin complex formation, factors that
      favor cell-cell adhesion. Complex 6 also attenuated the expression and secretion
      of the metastasis-relevant matrix metalloproteinases MMP-2 and MMP-9. In summary,
      coordination of apigenin and genistein to Cu(II) greatly enhances the antitumoral
      properties of these flavonoids and potentiates their mechanistic diversity. 

PMID- 23973683
TI  - Zinc complexes of salicylaldehydes: synthesis, characterization and DNA-binding
      properties.
AB  - The neutral mononuclear zinc complexes with substituted salicylaldehydes, in the
      absence or presence of a nitrogen donor heterocyclic ligand 2,2'-bipyridine or
      1,10-phenanthroline or 2,2'-dipyridylamine, have been synthesized and
      characterized by IR, UV and NMR spectroscopies. The experimental data suggest
      that salicylaldehyde is on deprotonated mode acting as a bidentate ligand
      coordinated to the metal ion through the phenolato and one aldehydo oxygen atoms.
      The crystal structures of bis(5-nitro-salicyladehydato)(2,2'
      dipyridylamine)zinc(II), bis(5-chloro-salicylaldehydato)(2,2'-bipyridine)zinc(II)
      monohydrate and bis(5-bromo-salicyladehydato)bis(methanol)zinc(II) have been
      determined with X-ray crystallography. The ability of the complexes to bind to
      calf-thymus DNA (CT DNA) has been studied by UV and fluorescence spectroscopy and
      viscosity measurements. UV studies of the interaction of the complexes with DNA
      have shown that they can bind to CT DNA. The calculated binding constants of the
      complexes to DNA reveal tight binding to DNA. The complexes can 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 complexes can displace the DNA-bound EB suggesting strong
      competition with EB for the intercalation site of DNA. 

PMID- 23973684
TI  - Monocytes in coronary artery disease and atherosclerosis: where are we now?
AB  - Despite improvements in interventional and pharmacological therapy of
      atherosclerotic disease, it is still the leading cause of death in the developed
      world. Hence, there is a need for further development of effective therapeutic
      approaches. This requires better understanding of the molecular mechanisms and
      pathophysiology of the disease. Atherosclerosis has long been identified as
      having an inflammatory component contributing to its pathogenesis, whereas the
      available therapy primarily targets hyperlipidemia and prevention of thrombosis.
      Notwithstanding a pleotropic anti-inflammatory effect to some therapies, such as
      acetyl salicylic acid and the statins, none of the currently approved medicines
      for management of either stable or complicated atherosclerosis has inflammation
      as a primary target. Monocytes, as representatives of the innate immune system,
      play a major role in the initiation, propagation, and progression of
      atherosclerosis from a stable to an unstable state. Experimental data support a
      role of monocytes in acute coronary syndromes and in outcome post-infarction;
      however, limited research has been done in humans. Analysis of expression of
      various cell surface receptors allows characterization of the different monocyte
      subsets phenotypically, whereas downstream assessment of inflammatory pathways
      provides an insight into their activity. In this review we discuss the functional
      role of monocytes and their different subpopulations in atherosclerosis, acute
      coronary syndromes, cardiac healing, and recovery with an aim of critical
      evaluation of potential future therapeutic targets in atherosclerosis and its
      complications. We will also discuss technical difficulties of delineating
      different monocyte subpopulations, understanding their differentiation potential
      and function. 

PMID- 23973685
TI  - Giant cardiac hydatid cyst: an uncommon cause of cardiomegaly.

PMID- 23973686
TI  - Impaired cardiac baroreflex sensitivity predicts response to renal sympathetic
      denervation in patients with resistant hypertension.
AB  - OBJECTIVES: This study sought to evaluate cardiac baroreflex sensitivity (BRS) as
      a predictor of response to renal sympathetic denervation (RDN). BACKGROUND:
      Catheter-based RDN is a novel treatment option for patients with resistant
      arterial hypertension. It is assumed that RDN reduces efferent renal and central
      sympathetic activity. METHODS: Fifty patients (age 60.3 +/- 13.8 years [mean +/-
      SD mean systolic blood pressure (BP) on ambulatory blood pressure monitoring
      (ABPM) 157 +/- 22 mm Hg, despite medication with 5.4 +/- 1.4 antihypertensive
      drugs) underwent RDN. Prior to RDN, a 30-min recording of continuous arterial BP
      (Finapres; TNO-TPD Biomedical Instrumentation, Amsterdam, the Netherlands) and
      high-resolution electrocardiography (1.6 kHz in orthogonal XYZ leads) was
      performed in all patients under standardized conditions. Cardiac BRS was assessed
      by phase-rectified signal averaging (BRSPRSA) according to previously published
      technologies. Response to RDN was defined as a reduction of mean systolic BP on
      ABPM by 10 mm Hg or more at 6 months after RDN. RESULTS: Six months after RDN,
      mean systolic BP on ABPM was significantly reduced from 157 +/- 22 mm Hg to 149
      +/- 20 mm Hg (p = 0.003). Twenty-six of the 50 patients (52%) were classified as
      responders. BRSPRSA was significantly lower in responders than nonresponders
      (0.16 +/- 0.75 ms/mm Hg vs. 1.54 +/- 1.73 ms/mm Hg; p < 0.001). Receiver-operator
      characteristics analysis revealed an area under the curve for prediction of
      response to RDN by BRSPRSA of 81.2% (95% confidence interval: 70.0% to 90.1%; p <
      0.001). On multivariable logistic regression analysis, reduced BRSPRSA was the
      strongest predictor of response to RDN, which was independent of all other
      variables tested. CONCLUSIONS: Impaired cardiac BRS identifies patients with
      resistant hypertension who respond to RDN.

PMID- 23973687
TI  - Ready for a marathon, not a sprint: renal denervation therapy for treatment
      resistant hypertension.

PMID- 23973688
TI  - Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular
      outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome
      with Low HDL/High Triglyceride and Impact on Global Health Outcomes).
AB  - OBJECTIVES: This study sought to examine the relationship between baseline and on
      study apolipoproteins (apo) A-1 and B and lipoprotein(a) [Lp(a)] levels and the
      development of subsequent cardiovascular (CV) events in the AIM-HIGH
      (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High
      Triglyceride and Impact on Global Health Outcomes) trial. BACKGROUND: Niacin has
      been reported to lower apoB and Lp(a) and to raise apoA-1. METHODS: Individuals
      with CV disease and low baseline levels of high-density lipoprotein cholesterol
      were randomized to simvastatin plus placebo or simvastatin, plus extended-release
      niacin ([ERN], 1,500 to 2,000 mg/day), with ezetimibe added as needed, in both
      groups, to maintain an on-treatment low-density lipoprotein cholesterol in the
      range of 40 to 80 mg/dl. Hazard ratios (HRs) were used to evaluate the
      relationship between levels of apoA-1, apoB, and Lp(a), and CV events in each
      treatment group. RESULTS: Baseline apoB and the apoB/apoA-I ratio were
      significantly predictive of CV events only for the placebo group (HR: 1.17 [p =
      0.018] and HR: 1.19 [p = 0.016]). Baseline and on-study Lp(a) were predictive of
      CV events in both simvastatin plus placebo (baseline HR: 1.24 [p = 0.002] and on
      study HR: 1.21 [p = 0.017]) and the simvastatin plus ERN group (baseline HR: 1.25
      [p = 0.001] and on-study HR: 1.18 [p = 0.028]). The ERN modestly increased 1-year
      apoA-1 (7%), decreased apoB (13%), decreased the ApoB/ApoA-1 ratio (19%), and
      decreased Lp(a) 21%, but did not reduce CV events. CONCLUSIONS: Lp(a) was
      associated with increased CV risk in both treatment groups indicating that it
      contributes to residual CV risk. However, there was no evidence that ERN reduced
      CV risk, despite favorable lipoprotein changes.

PMID- 23973689
TI  - Non-high-density lipoprotein cholesterol, guideline targets, and population
      percentiles for secondary prevention in 1.3 million adults: the VLDL-2 study
      (very large database of lipids).
AB  - OBJECTIVES: This study sought to examine patient-level discordance between
      population percentiles of non-high-density lipoprotein cholesterol (HDL-C) and
      low-density lipoprotein cholesterol (LDL-C). BACKGROUND: Non-HDL-C is an
      alternative to LDL-C for risk stratification and lipid-lowering therapy. The
      justification for the present guideline-based non-HDL-C cutpoints of 30 mg/dl
      higher than the LDL-C cutpoints remains largely untested. METHODS: We assigned
      population percentiles to non-HDL-C and Friedewald-estimated LDL-C values of
      1,310,440 U.S. adults with triglyceride levels <400 mg/dl who underwent lipid
      testing by vertical spin density gradient ultracentrifugation (Atherotech,
      Birmingham, Alabama) from 2009 to 2011. RESULTS: LDL-C cutpoints of 70, 100, 130,
      160, and 190 mg/dl were in the same population percentiles as non-HDL-C values of
      93, 125, 157, 190, and 223 mg/dl, respectively. Non-HDL-C values reclassified a
      significant proportion of patients within or to a higher treatment category
      compared with Friedewald LDL-C values, especially at LDL-C levels in the
      treatment range of high-risk patients and at triglyceride levels >=150 mg/dl. Of
      patients with LDL-C levels <70 mg/dl, 15% had a non-HDL-C level >= 100 mg/dl
      (guideline-based cutpoint) and 25% had a non-HDL-C level >= 93 mg/dl (percentile
      based cutpoint); if triglyceride levels were 150 to 199 mg/dl concurrently, these
      values were 22% and 50%, respectively. CONCLUSIONS: There is significant patient
      level discordance between non-HDL-C and LDL-C percentiles at lower LDL-C and
      higher triglyceride levels, which has implications for the treatment of high-risk
      patients. Current non-HDL-C cutpoints for high-risk patients may need to be
      lowered to match percentiles of LDL-C cutpoints. Relatively small absolute
      reductions in non-HDL-C cutpoints result in substantial reclassification of
      patients to higher treatment categories with potential implications for risk
      assessment and treatment.

PMID- 23973691
TI  - Infant congenital aortic valve stenosis: the pendulum swings.

PMID- 23973690
TI  - Cardiomyocyte injury assessed by a highly sensitive troponin assay and sudden
      cardiac death in the community: the Cardiovascular Health Study.
AB  - OBJECTIVES: This study sought to determine the association between markers of
      cardiomyocyte injury in ambulatory subjects and sudden cardiac death (SCD).
      BACKGROUND: The pathophysiology of SCD is complex but is believed to be
      associated with an abnormal cardiac substrate in most cases. The association
      between biomarkers of cardiomyocyte injury in ambulatory subjects and SCD has not
      been investigated. METHODS: Levels of cardiac troponin T, a biomarker of
      cardiomyocyte injury, were measured by a highly sensitive assay (hsTnT) in 4,431
      ambulatory participants in the Cardiovascular Health Study, a longitudinal
      community-based prospective cohort study. Serial measures were obtained in 3,089
      subjects. All deaths, including SCD, were adjudicated by a central events
      committee. RESULTS: Over a median follow-up of 13.1 years, 246 participants had
      SCD. Baseline levels of hsTnT were significantly associated with SCD (hazard
      ratio [HR] for +1 log(hsTnT): 2.04, 95% confidence interval [CI]: 1.78 to 2.34].
      This association persisted in covariate-adjusted Cox analyses accounting for
      baseline risk factors (HR: 1.30, 95% CI: 1.05 to 1.62), as well as for incident
      heart failure and myocardial infarction (HR: 1.26, 95% CI: 1.01 to 1.57). The
      population was also categorized into 3 groups based on baseline hsTnT levels and
      SCD risk [fully adjusted HR: 1.89 vs. 1.55 vs. 1 (reference group) for hsTnT
      >=12.10 vs. 5.01 to 12.09 vs. <= 5.00 pg/ml, respectively; p trend = 0.005]. On
      serial measurements, change in hsTnT levels was also associated with SCD risk
      (fully adjusted HR for +1 pg/ml per year increase from baseline: 1.03, 95% CI:
      1.01 to 1.06). CONCLUSIONS: The findings suggest an association between
      cardiomyocyte injury in ambulatory subjects and SCD risk beyond that of
      traditional risk factors.

PMID- 23973692
TI  - Ganglionated plexus ablation in patients undergoing pulmonary vein isolation for
      paroxysmal atrial fibrillation: here we go again.

PMID- 23973694
TI  - Autonomic denervation added to pulmonary vein isolation for paroxysmal atrial
      fibrillation: a randomized clinical trial.
AB  - OBJECTIVES: The aim of this study was to investigate whether the combination of
      conventional pulmonary vein isolation (PVI) by circumferential antral ablation
      with ganglionated plexi (GP) modification in a single ablation procedure, yields
      higher success rates than PVI or GP ablation alone, in patients with paroxysmal
      atrial fibrillation (PAF). BACKGROUND: Conventional PVI transects the major left
      atrial GP, and it is possible that autonomic denervation by inadvertent GP
      ablation plays a central role in the efficacy of PVI. METHODS: A total of 242
      patients with symptomatic PAF were recruited and randomized as follows: 1)
      circumferential PVI (n = 78); 2) anatomic ablation of the main left atrial GP (n
      = 82); or 3) circumferential PVI followed by anatomic ablation of the main left
      atrial GP (n = 82). The primary endpoint was freedom from atrial fibrillation
      (AF) or other sustained atrial tachycardia (AT), verified by monthly visits,
      ambulatory electrocardiographic monitoring, and implantable loop recorders,
      during a 2-year follow-up period. RESULTS: Freedom from AF or AT was achieved in
      44 (56%), 39 (48%), and 61 (74%) patients in the PVI, GP, and PVI+GP groups,
      respectively (p = 0.004 by log-rank test). PVI+GP ablation strategy compared with
      PVI alone yielded a hazard ratio of 0.53 (95% confidence interval: 0.31 to 0.91;
      p = 0.022) for recurrence of AF or AT. Fluoroscopy duration was 16 +/- 3 min, 20
      +/- 5 min, and 23 +/- 5 min for PVI, GP, and PVI+GP groups, respectively (p <
      0.001). Post-ablation atrial flutter did not differ between groups: 5.1% in PVI,
      4.9% in GP, and 6.1% in PVI+GP. No serious adverse procedure-related events were
      encountered. CONCLUSIONS: Addition of GP ablation to PVI confers a significantly
      higher success rate compared with either PVI or GP alone in patients with PAF.

PMID- 23973693
TI  - Low levels of high-density lipoprotein cholesterol and increased risk of
      cardiovascular events in stable ischemic heart disease patients: A post-hoc
      analysis from the COURAGE Trial (Clinical Outcomes Utilizing Revascularization
      and Aggressive Drug Evaluation).
AB  - OBJECTIVES: This study sought to assess the independent effect of high-density
      lipoprotein-cholesterol (HDL-C) level on cardiovascular risk in patients with
      stable ischemic heart disease (SIHD) who were receiving optimal medical therapy
      (OMT). BACKGROUND: Although low HDL-C level is a powerful and independent
      predictor of cardiovascular risk, recent data suggest that this may not apply
      when low-density lipoprotein-cholesterol (LDL-C) is reduced to optimal levels
      using intensive statin therapy. METHODS: We performed a post-hoc analysis in
      2,193 men and women with SIHD from the COURAGE trial. The primary outcome measure
      was the composite of death from any cause or nonfatal myocardial infarction (MI).
      The independent association between HDL-C levels measured after 6 months on OMT
      and the rate of cardiovascular events after 4 years was assessed. Similar
      analyses were performed separately in subjects with LDL-C levels below 70 mg/dl
      (1.8 mmol/l). RESULTS: In the overall population, the rate of death/MI was 33%
      lower in the highest HDL-C quartile as compared with the lowest quartile, with
      quartile of HDL-C being a significant, independent predictor of death/MI (p =
      0.05), but with no interaction for LDL-C category (p = 0.40). Among subjects with
      LDL-C levels <70 mg/dl, those in the highest quintile of HDL-C had a 65% relative
      risk reduction in death or MI as compared with the lowest quintile, with HDL-C
      quintile demonstrating a significant, inverse predictive effect (p = 0.02).
      CONCLUSIONS: In this post-hoc analysis, patients with SIHD continued to
      experience incremental cardiovascular risk associated with low HDL-C levels
      despite OMT during long-term follow-up. This relationship persisted and appeared
      more prominent even when LDL-C was reduced to optimal levels with intensive
      dyslipidemic therapy. (Clinical Outcomes Utilizing Revascularization and
      Aggressive Drug Evaluation; NCT00007657).

PMID- 23973695
TI  - Ca(2+) leak in atrial fibrillation: junctophilin-2 stabilizes ryanodine receptor.

PMID- 23973697
TI  - High-density lipoprotein and residual cardiovascular risk: De minimis non curat
      medicus or the COURAGE to be SMART?

PMID- 23973696
TI  - Mutation E169K in junctophilin-2 causes atrial fibrillation due to impaired RyR2
      stabilization.
AB  - OBJECTIVES: This study sought to study the role of junctophilin-2 (JPH2) in
      atrial fibrillation (AF). BACKGROUND: JPH2 is believed to have an important role
      in sarcoplasmic reticulum (SR) Ca(2+) handling and modulation of ryanodine
      receptor Ca(2+) channels (RyR2). Whereas defective RyR2-mediated Ca(2+) release
      contributes to the pathogenesis of AF, nothing is known about the potential role
      of JPH2 in atrial arrhythmias. METHODS: Screening 203 unrelated hypertrophic
      cardiomyopathy patients uncovered a novel JPH2 missense mutation (E169K) in 2
      patients with juvenile-onset paroxysmal AF (pAF). Pseudoknock-in (PKI) mouse
      models were generated to determine the molecular defects underlying the
      development of AF caused by this JPH2 mutation. RESULTS: PKI mice expressing
      E169K mutant JPH2 exhibited a higher incidence of inducible AF than wild type
      (WT)-PKI mice, whereas A399S-PKI mice expressing a hypertrophic cardiomyopathy
      linked JPH2 mutation not associated with atrial arrhythmias were not
      significantly different from WT-PKI. E169K-PKI but not A399A-PKI atrial
      cardiomyocytes showed an increased incidence of abnormal SR Ca(2+) release
      events. These changes were attributed to reduced binding of E169K-JPH2 to RyR2.
      Atrial JPH2 levels in WT-JPH2 transgenic, nontransgenic, and JPH2 knockdown mice
      correlated negatively with the incidence of pacing-induced AF. Ca(2+) spark
      frequency in atrial myocytes and the open probability of single RyR2 channels
      from JPH2 knockdown mice was significantly reduced by a small JPH2-mimicking
      oligopeptide. Moreover, patients with pAF had reduced atrial JPH2 levels per RyR2
      channel compared to sinus rhythm patients and an increased frequency of
      spontaneous Ca(2+) release events. CONCLUSIONS: Our data suggest a novel
      mechanism by which reduced JPH2-mediated stabilization of RyR2 due to loss-of
      function mutation or reduced JPH2/RyR2 ratios can promote SR Ca(2+) leak and
      atrial arrhythmias, representing a potential novel therapeutic target for AF.

PMID- 23973698
TI  - Effect of treatment for 12 weeks with rilapladib, a lipoprotein-associated
      phospholipase A2 inhibitor, on arterial inflammation as assessed with 18F
      fluorodeoxyglucose-positron emission tomography imaging.

PMID- 23973699
TI  - Zotarolimus- versus everolimus-eluting stents for unprotected left main coronary
      artery disease.
AB  - OBJECTIVES: This study sought to compare the safety and efficacy of the
      zotarolimus-eluting stent (ZES) and the everolimus-eluting stent (EES) for
      treatment of unprotected left main coronary artery (uLMCA) disease. BACKGROUND:
      The second-generation ZES and EES have reduced the risk of restenosis in large
      patient cohorts. However, their comparative performance in uLMCA lesions is not
      known. METHODS: In this study, patients with symptomatic coronary artery disease
      undergoing percutaneous coronary intervention for uLMCA lesions were randomly
      assigned to receive either a ZES (n = 324) or an EES (n = 326). The primary
      endpoint was the combined incidence of death, myocardial infarction, and target
      lesion revascularization at 1 year. Secondary endpoints were definite or probable
      stent thrombosis at 1 year and angiographic restenosis based on analysis of the
      left main coronary artery area at follow-up angiography. RESULTS: At 1 year, the
      cumulative incidence of the primary endpoint was 17.5% in the ZES group and 14.3%
      in the EES group (relative risk: 1.26; 95% confidence interval [CI]: 0.85 to
      1.85; p = 0.25). Three patients in the ZES group (0.9%) and 2 patients in the EES
      group (0.6%) experienced definite or probable stent thrombosis (p > 0.99). All
      cause mortality at 1 year was equal in the 2 groups (5.6%; relative risk: 1.00;
      95% CI: 0.52 to 1.93; p = 0.98). Angiographic restenosis occurred in 21.5% of
      patients in the ZES group and 16.8% in the EES group (relative risk: 1.28; 95%
      CI: 0.86 to 1.92; p = 0.24). CONCLUSIONS: Within the statistical limitations of
      the present study, treatment of uLMCA lesions with a ZES or an EES provided
      comparable clinical and angiographic outcomes at 1-year follow-up.

PMID- 23973700
TI  - Macrophage-stem cell crosstalk after myocardial infarction.

PMID- 23973702
TI  - Should we measure quality by the dose?

PMID- 23973701
TI  - Beyond medication prescription as performance measures: optimal secondary
      prevention medication dosing after acute myocardial infarction.
AB  - OBJECTIVES: The aim of this study was to examine the prescribing patterns of
      medications quantified by the performance measures for acute myocardial
      infarction (AMI). BACKGROUND: Current performance measures for AMI are designed
      to improve quality by quantifying the use of evidence-based treatments. However,
      these measures only assess medication prescription. Whether patients receive
      optimal dosing of secondary prevention medications at the time of and after
      discharge after AMI is unknown. METHODS: We assessed treatment doses of beta
      blockers, statins, and angiotensin-converting enzyme inhibitors
      (ACEI)/angiotensin II receptor blockers (ARBs) at discharge and 12 months after
      AMI among 6,748 patients from 31 hospitals enrolled in 2 U.S. registries (2003 to
      2008). Prescribed doses were categorized as none, low (<50% target [defined from
      seminal clinical trials]), moderate (50% to 74% target), or goal (>= 75% target).
      Patients with contraindications were excluded from analyses for that medication.
      RESULTS: Most eligible patients (>87%) were prescribed some dose of each
      medication at discharge, although only 1 in 3 patients were prescribed these
      medications at goal doses. Of patients not discharged on goal doses, up-titration
      during follow-up occurred infrequently (approximately 25% of patients for each
      medication). At 12 months, goal doses of beta-blockers, statins, and ACEI/ARBs
      were achieved in only 12%, 26%, and 32% of eligible patients, respectively. After
      multivariable adjustment, prescription of goal dose at discharge was strongly
      associated with being at goal dose at follow-up: beta-blockers, adjusted odds
      ratio (OR): 6.08 (95% confidence interval [CI]: 3.70 to 10.01); statins, adjusted
      OR: 8.22 (95% CI: 6.20 to 10.90); ACEI/ARBs, adjusted OR: 5.80 (95% CI: 2.56 to
      13.16); p < 0.001 for each. CONCLUSIONS: Although nearly all patients after an
      AMI are discharged on appropriate secondary prevention medications, dose
      increases occur infrequently, and most patients are prescribed doses below those
      with proven efficacy in clinical trials. Integration of dose intensity into
      performance measures might help improve the use of optimal medical therapy after
      AMI.

PMID- 23973703
TI  - Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of
      dyslipidemia and atherosclerosis.
AB  - Hypercholesterolemia is a major risk factor for cardiovascular diseases,
      increasing the incidence of myocardial infarction and death. Statin-induced
      lowering of low-density lipoprotein cholesterol (LDL-C) reduces cardiovascular
      morbidity and mortality. However, many individuals treated with statins do not
      achieve their target levels of LDL-C, and thus, LDL-associated residual risk
      remains. Gain-of-function mutations of the proprotein convertase subtilisin/kexin
      type 9 (PCSK9) are associated with hypercholesterolemia and increased risk of
      cardiovascular events. Conversely, loss-of-function mutations are linked to low
      plasma LDL-C levels and a reduction of cardiovascular risk without known unwanted
      effects on individual health. Experimental studies have revealed that PCSK9
      reduces the hepatic uptake of LDL-C by increasing the endosomal and lysosomal
      degradation of LDL receptors (LDLR). Low intracellular cholesterol levels in
      response to statin treatment activate the sterol regulatory element-binding
      protein-2 (SREBP-2), resulting in coexpression of LDLR and PCSK9. Although this
      self-regulatory mechanism contributes to maintain cholesterol homeostasis
      preventing excessive cholesterol uptake, it may limit the therapeutic effect of
      statins. A number of clinical studies have demonstrated that inhibition of PCSK9
      alone and in addition to statins potently reduces serum LDL-C concentrations.
      Moreover, experimental studies indicate that PCSK9 might accelerate
      atherosclerosis by promoting inflammation, endothelial dysfunction, and
      hypertension by mechanisms independent of the LDLR. Further research is needed to
      characterize the potential therapeutic and to rule out unwanted off-target
      effects of PCSK9 inhibition. In this review we elucidate the role of PCSK9 in
      lipid homeostasis, highlight the impact of PCSK9 on atherosclerosis, and
      summarize current therapeutic strategies targeting PCSK9. 

PMID- 23973704
TI  - Macrophage subpopulations are essential for infarct repair with and without stem
      cell therapy.
AB  - OBJECTIVES: This study sought to investigate the hypothesis that the favorable
      effects of mesenchymal stromal cells (MSCs) on infarct repair are mediated by
      macrophages. BACKGROUND: The favorable effects of MSC therapy in myocardial
      infarction (MI) are complex and not fully understood. METHODS: We induced MI in
      mice and allocated them to bone marrow MSCs, mononuclear cells, or saline
      injection into the infarct, with and without early (4 h before MI) and late (3
      days after MI) macrophage depletion. We then analyzed macrophage phenotype in the
      infarcted heart by flow cytometry and macrophage secretome in vitro. Left
      ventricular remodeling and global and regional function were assessed by
      echocardiography and speckle-tracking based strain imaging. RESULTS: The MSC
      therapy significantly increased the percentage of reparative M2 macrophages
      (F4/80(+)CD206(+)) in the infarcted myocardium, compared with mononuclear- and
      saline-treated hearts, 3 and 4 days after MI. Macrophage cytokine secretion,
      relevant to infarct healing and repair, was significantly increased after MSC
      therapy, or incubation with MSCs or MSC supernatant. Significantly, with and
      without MSC therapy, transient macrophage depletion increased mortality 30 days
      after MI. Furthermore, early macrophage depletion produced the greatest negative
      effect on infarct size and left ventricular remodeling and function, as well as a
      significant incidence of left ventricular thrombus formation. These deleterious
      effects were attenuated with macrophage restoration and MSC therapy. CONCLUSIONS:
      Some of the protective effects of MSCs on infarct repair are mediated by
      macrophages, which are essential for early healing and repair. Thus, targeting
      macrophages could be a novel strategy to improve infarct healing and repair.

PMID- 23973705
TI  - Highly sensitive troponin assay and sudden cardiac death in the community:
      unlocking the pathophysiology of sudden cardiac death one biomarker at a time.

PMID- 23973706
TI  - Finding time.
AB  - We understand time through our models of it. These are typically models of our
      physical chronometers, which we then project into our subjects. A few of these
      models of the nature of time and its effects on the behavior of organisms are
      reviewed. New models, such as thermodynamics and spectral decomposition, are
      recommended for the potential insights that they afford. In all cases,
      associations are essential features of timing. To make them, time must be
      discretized by stimuli such as hours, minutes, conditioned stimuli, trials, and
      contexts in general. Any one association is seldom completely dominant, but
      rather shares control through proximity in a multidimensional space, important
      dimensions of which may include physical space and time as rendered by Fourier
      transforms. 

PMID- 23973707
TI  - Reproductive effort and success of wild female mallards: does male quality
      matter?
AB  - In accordance with the differential allocation hypothesis, females are expected
      to increase their reproductive investment when mated to high-quality males. In
      waterfowl, reproductive, investment increased when captive female mallards (Anas
      platyrhynchos) were mated to more attractive males, but information for wild
      ducks is lacking. Studies of waterfowl mating systems have focused primarily on
      the importance of plumage coloration of males and female mate choice, whereas
      investigations of reproductive ecology examine female attributes and virtually
      ignore the role of males in investment decisions. Here, we used unique data for
      253 pairs of wild mallards to test whether females mated to high-quality males
      would increase reproductive effort and reproduce more successfully. We derived
      measurements of female and male body size and condition, and indices of male
      plumage quality, and related these traits to patterns of reproductive effort and
      performance of females. Consistent with predictions, yearling females nested
      earlier and had higher nest survival when mated to males with better plumage
      scores. Furthermore, when paired with larger bodied males, yearling females
      renested more often, and nest and brood survival increased among older females.
      Although the strength of male effects varied with breeding stage and female age
      or experience, this is one of a few studies to demonstrate an additive effect of
      male quality on investment and success of females, in free-ranging birds. 

PMID- 23973708
TI  - The amygdala: a potential player in timing CS-US intervals.
AB  - Pavlovian conditioning is the reference paradigm for the study of associative
      learning based on the programmed relation of two stimuli, the conditioned
      stimulus (CS) and the unconditioned stimulus (US). Some authors believe that
      learning the CS-US interval is a co-requisite of or a pre-requisite to learning
      the CS-US association. There is a substantial literature showing that the
      amygdala is a critical player in Pavlovian conditioning, with both aversive and
      appetitive USs. We review a sparse but growing body of literature suggesting that
      the amygdala may also participate in processing the timing of the CS-US interval.
      We discuss whether the amygdala, in particular its central, basal and lateral
      nuclei, in concert with the network it belongs to, may play a role in learning
      the CS-US interval. We also suggest new and dedicated strategies that would
      result in better knowledge of the neural mechanisms underlying the learning of
      the CS-US time interval in isolation from the CS-US association. 

PMID- 23973709
TI  - Road to the elimination of schistosomiasis from Asia: the journey is far from
      over.
AB  - Schistosomiasis is a neglected tropical disease with a very long endemic history
      in Asia. Great strides have been made to control the disease in China and the
      Philippines but the road to elimination is far from over, given the zoonotic
      nature of the schistosome parasites in both countries. 

PMID- 23973710
TI  - miR-143 decreases COX-2 mRNA stability and expression in pancreatic cancer cells.
AB  - Small non-coding RNAs, microRNAs (miRNA), inhibit the translation or accelerate
      the degradation of message RNA (mRNA) by targeting the 3'-untranslated region (3'
      UTR) in regulating growth and survival through gene suppression. Deregulated
      miRNA expression contributes to disease progression in several cancers types,
      including pancreatic cancers (PaCa). PaCa tissues and cells exhibit decreased
      miRNA, elevated cyclooxygenase (COX)-2 and increased prostaglandin E2 (PGE2)
      resulting in increased cancer growth and metastases. Human PaCa cell lines were
      used to demonstrate that restoration of miRNA-143 (miR-143) regulates COX-2 and
      inhibits cell proliferation. miR-143 were detected at fold levels of 0.41 +/-
      0.06 in AsPC-1, 0.20 +/- 0.05 in Capan-2 and 0.10 +/- 0.02 in MIA PaCa-2. miR-143
      was not detected in BxPC-3, HPAF-II and Panc-1 which correlated with elevated
      mitogen-activated kinase (MAPK) and MAPK kinase (MEK) activation. Treatment with
      10 MUM of MEK inhibitor U0126 or PD98059 increased miR-143, respectively, by 187
      +/- 18 and 152 +/- 26-fold in BxPC-3 and 182 +/- 7 and 136 +/- 9-fold in HPAF-II.
      miR-143 transfection diminished COX-2 mRNA stability at 60 min by 2.6 +/- 0.3
      fold in BxPC-3 and 2.5 +/- 0.2-fold in HPAF-II. COX-2 expression and cellular
      proliferation in BxPC-3 and HPAF-II inversely correlated with increasing miR-143.
      PGE2 levels decreased by 39.3 +/- 5.0% in BxPC-3 and 48.0 +/- 3.0% in HPAF-II
      transfected with miR-143. Restoration of miR-143 in PaCa cells suppressed of COX
      2, PGE2, cellular proliferation and MEK/MAPK activation, implicating this pathway
      in regulating miR-143 expression.

PMID- 23973711
TI  - Statin induces inhibition of triple negative breast cancer (TNBC) cells via PI3K
      pathway.
AB  - Primary TNBCs are treated as if they were a single disease entity, yet it is
      clear they do not behave as a single entity in response to current therapies.
      Recently, we reported that statins might have a potential benefit for TNBCs
      associated with ets-1 overexpression. The aim of this study is to investigate the
      role of PTEN loss in the effects of statin on TNBC cells. In addition, we analyze
      the relationship between AKT downstream pathways and the effects of statin on
      TNBC cells. We investigated the effect of a statin on TNBC cells and analyzed the
      association of PI3K pathways using various TNBC cells in terms of PTEN loss and
      AKT pathways. Simvastatin treatments resulted in decreased cell viabilities in
      various TNBC cell lines. Compared with PTEN wild-type TNBC cells, PTEN mutant
      type TNBC cells showed a decreased response to simvastatin. Expressions of
      phosphorylated Akt and total Akt showed an inverse relationship with PTEN
      expression. The TNBC cell lines, which showed increased expression of p-Akt,
      appeared to attenuate the expression of p-Akt by PTEN loss in simvastatin-treated
      TNBC cells. The Akt inhibitor, LY294002, augmented the effect of simvastatin on
      PTEN wild-type TNBC cells. Simvastatin induces inhibition of TNBC cells via PI3K
      pathway activation. 

PMID- 23973712
TI  - Extracellular lipid metabolism influences the survival of ovarian cancer cells.
AB  - Lysophosphatidic acid (LPA) is an extracellular lipid mediator consisting of a
      fatty acid and a phosphate group linked to the glycerol backbone. Here, we show
      that 1-oleoyl- and 1-palmitoyl-LPA, but not 1-stearoyl- or alkyl-LPA, enhance
      HNOA ovarian cancer cell survival. Other lysophospholipids with oleic or lauric
      acid, but not stearic acid, also induce the survival effects. HNOA cells have the
      lipase activities that cleave LPA to generate fatty acid. Oleic acid stimulates
      HNOA cell survival via increased glucose utilization. Our findings suggest that
      extracellular lysolipid metabolism might play an important role in HNOA cell
      growth. 

PMID- 23973713
TI  - Cetuximab enhances TRAIL-induced gastric cancer cell apoptosis by promoting DISC
      formation in lipid rafts.
AB  - TRAIL is a member of the tumor necrosis factor family that selectively induces
      cancer cell apoptosis. However, gastric cancer cells are insensitive to TRAIL.
      Our and others studies showed that the inhibition of EGFR pathway activation
      could increase the sensitivity of TRAIL in cancer cells. But the detailed
      mechanism is not fully understood. In the present study, compared with TRAIL or
      cetuximab (an anti-EGFR monoclonal antibody) alone, treatment with the
      TRAIL/cetuximab combination significantly promoted death receptor 4 (DR4)
      clustering as well as the translocation of both DR4 and Fas-associated death
      domain-containing protein (FADD) into lipid rafts. This in turn resulted in
      caspase-8 cleavage and the formation of the death-inducing signaling complex
      (DISC) in these lipid rafts. Cholesterol-depletion with methyl-beta-cyclodextrin
      partially prevented DR4 clustering and DISC formation, and thus partially
      reversed apoptosis induced by the TRAIL/cetuximab dual treatment. These results
      indicate that cetuximab increases TRAIL-induced gastric cancer cell apoptosis at
      least partially through the promotion of DISC formation in lipid rafts. 

PMID- 23973714
TI  - Identification of the variants in PARL, the nuclear modifier gene, responsible
      for the expression of LHON patients in Thailand.
AB  - The present study explored variation in the PARL gene as one of the potential
      nuclear modifiers in the pathogenesis of Leber hereditary optic neuropathy
      (LHON). Ten exons, their franking introns and 3' UTR of the PARL gene were
      analysed. Seventeen SNPs detected were investigated in 83 affected and 53
      unaffected individuals from 47 independent Thai LHON pedigrees using MQLS
      statistics in order to minimize the influence of the family background. Three
      intronic SNPs (rs953419, rs3749446 and rs1402000) showed statistically
      significant results. Joint haplotypes were constructed based on the genotypes at
      3 SNPs and 7 possible haplotypes were observed in the 136 subjects. Our findings
      that the frequency of the haplotype AAC, and AAT were significantly higher in the
      unaffected cases and the frequencies of haplotype GGT were significantly higher
      in LHON cases, indicate that it might have a role in the penetrance of this
      mitochondrial disease. 

PMID- 23973715
TI  - Lipid order, saturation and surface property relationships: a study of human
      meibum saturation.
AB  - Tear film stability decreases with age however the cause(s) of the instability
      are speculative. Perhaps the more saturated meibum from infants may contribute to
      tear film stability. The meibum lipid phase transition temperature and lipid
      hydrocarbon chain order at physiological temperature (33  degrees C) decrease
      with increasing age. It is reasonable that stronger lipid-lipid interactions
      could stabilize the tear film since these interactions must be broken for tear
      break up to occur. In this study, meibum from a pool of adult donors was
      saturated catalytically. The influence of saturation on meibum hydrocarbon chain
      order was determined by infrared spectroscopy. Meibum is in an anhydrous state in
      the meibomian glands and on the surface of the eyelid. The influence of
      saturation on the surface properties of meibum was determined using Langmuir
      trough technology. Saturation of native human meibum did not change the minimum
      or maximum values of hydrocarbon chain order so at temperatures far above or
      below the phase transition of human meibum, saturation does not play a role in
      ordering or disordering the lipid hydrocarbon chains. Saturation did increase the
      phase transition temperature in human meibum by over 20  degrees C, a relatively
      high amount. Surface pressure-area studies showing the late take off and higher
      maximum surface pressure of saturated meibum compared to native meibum suggest
      that the saturated meibum film is quite molecularly ordered (stiff molecular
      arrangement) and elastic (molecules are able to rearrange during compression and
      expansion) compared with native meibum films which are more fluid agreeing with
      the infrared spectroscopic results of this study. In saturated meibum, the
      formation of compacted ordered islands of lipids above the surfactant layer would
      be expected to decrease the rate of evaporation compared to fluid and more
      loosely packed native meibum. Higher surface pressure observed with films of
      saturated meibum compared to native meibum suggests greater film stability
      especially under the high shear stress of a blink. 

PMID- 23973716
TI  - Tear film stability: a review.
AB  - Tear film stability can be assessed via a number of tools designed for clinical
      as well as research purposes. These techniques can give us insights into the tear
      film, and allow assessment of conditions that can lead to dry eye symptoms, and
      in severe cases, to significant ocular surface damage and deterioration of
      vision. Understanding what drives tear film instability and its assessment is
      also crucial for evaluating existing and new therapies. This review examines
      various techniques that are used to assess tear film instability: evaluation of
      tear break-up time and non-invasive break-time; topographic and interferometric
      techniques; confocal microscopic methods; aberrometry; and visual function tests.
      It also describes possible contributions of different tear film components;
      namely meibomian lipids, ocular mucins and proteins, and factors such as age,
      contact lens wear, ocular surgery and environmental stimuli, that may influence
      tear film instability. 

PMID- 23973717
TI  - Bacterial cellulose membranes as drug delivery systems: an in vivo skin
      compatibility study.
AB  - Bacterial cellulose (BC) is a highly pure form of cellulose, produced in the form
      of a swollen membrane by several bacteria that demonstrated to be able to
      modulate the skin release of model drugs. In the present study, the skin
      irritation potential of BC was evaluated in human subjects. BC membranes with and
      without glycerin (acting as plasticizer) were tested. No significant differences
      were observed for transepidermal water loss (TEWL) measurements in comparison
      with negative control, 2 and 24 h after patch removal, which is an indicator of
      an absence of barrier disruption. Similar results were found for erythema.
      Clinical scores were zero at both times for all volunteers, with the exception of
      five volunteers that exhibited weak reactions. BC with glycerin provided a skin
      moisturizing effect statistically higher than the negative control (p=0.044),
      which was not observed for BC alone. The good skin tolerance found after a single
      application under occlusion reinforces the putative interest of BC membranes as
      supports for drug topical delivery. Besides modifying the mechanical properties,
      the inclusion of glycerin results in a skin moisturizing effect which could be
      clinically relevant for the treatment for skin diseases characterized by dryness,
      such as psoriasis and atopic dermatitis.

PMID- 23973718
TI  - Informality and the expansion of social protection programs: evidence from
      Mexico.
AB  - Many countries are moving from employer-based to universal health coverage, which
      can generate crowd out. In Mexico, Seguro Popular provides public health coverage
      to the uninsured. Using the gradual roll-out of the system at the municipality
      level, we estimate that Seguro Popular had no effect on informality in the
      overall population. Informality did increase by 1.7% for less educated workers,
      but the wage gains for workers who switch between the formal and the informal
      sector were not significantly affected. This suggests that marginal workers do
      not choose between formal and informal jobs on the basis of health insurance
      coverage. 

PMID- 23973719
TI  - The importance of association between angiotensin-converting enzyme (ACE) Gene
      I/D polymorphism and diabetic peripheral neuropathy.
AB  - BACKGROUND: Diabetic peripheral neuropathy (DPN) is a microvascular complication
      of diabetes mellitus (DM) due to decreasing quality of life. In the present
      study, it is aimed to evaluate angiotensin-converting enzyme (ACE) Gene I/D
      polymorphism in Turkish population. MATERIALS AND METHODS: Two hundred and thirty
      five DPN patients and two hundred and eighty-one controls were enrolled in this
      study. Genomic DNA was isolated and genotyped using polymerase chain reaction
      (PCR) analyses for the ACE gene I/D polymorphism. RESULTS: Baseline
      characteristics of the DPN patients according to ACE genotypes were similar,
      except for history of hypertension. The frequency of II genotype was
      significantly higher in patients with positive history of hypertension than the
      patients with negative history of hypertension (p=0.013). DD genotype of I/D
      polymorphism was found to be a susceptibility factor for DPN in homozygous form
      (p=0.032). According to allele frequencies, D allele of I/D polymorphism was
      found to be a susceptibility factor for DPN (p=0.031). CONCLUSION: ACE gene I/D
      polymorphism may research in DM patients to determine genetic predisposition for
      DPN. It can be useful for taking early measures and avoiding DPN in a Turkish
      population.

PMID- 23973720
TI  - Infantile parkinsonism and GABAergic hypotransmission in a patient with pyruvate
      carboxylase deficiency.
AB  - Pyruvate carboxylase deficiency is a rare metabolic disorder, with three
      different phenotypes. We aim to report the case of a newborn presenting the
      severe neonatal form of this deficiency (the B or "French" phenotype, hypokinesia
      and rigidity being the main features) and the results of the study of classic
      neurotransmitters involved in movement control. Hyperdopaminergic transmission
      (both in the cerebrospinal fluid and in the substantia nigra) and hypoGABAergic
      transmission (in the substantia nigra) were found. Both gamma-aminobutyric acid
      and dopamine markers were found coexisting in individual neurons of the
      substantia nigra. This is the first time this phenomenon has been reported in the
      literature. We discuss the possible role of GABAergic deficiency, its interaction
      with other neurotransmitters and its implication in neurotransmitter homeostasis.
      A better comprehension of that field would increase understanding of the
      pathophysiology of neurological symptoms and neurotransmitter plasticity. 

PMID- 23973721
TI  - The identification and characterisation of a new deltamethrin resistance
      associated gene, UBL40, in the diamondback moth, Plutella xylostella (L.).
AB  - Differential expression of ubiquitin was previously reported between Plutella
      xylostella strains that are resistant or susceptible to the pesticide
      deltamethrin (DM). This finding hinted at the potential involvement of ubiquitin
      in deltamethrin resistance, a theory that demanded further testing. Real-time PCR
      analyses revealed that one of the ubiquitin genes, UBL40, was overexpressed in
      the deltamethrin-resistant strain during the fourth instar. To investigate the
      functional relationship between this gene and deltamethrin resistance, RNA
      interference (RNAi) and cell transfection were utilised. UBL40 knockdown was
      observed to significantly reduce the level of resistance in RNAi-treated larvae
      after 48 h. Conversely, overexpression of UBL40 in Drosophila Kc cells conferred
      a degree of protection against deltamethrin. These results represent the first
      evidence that UBL40 plays a role in the regulation of deltamethrin resistance in
      P. xylostella.

PMID- 23973722
TI  - Jumping and gliding rodents: mitogenomic affinities of Pedetidae and Anomaluridae
      deduced from an RNA-Seq approach.
AB  - An RNA-Seq strategy was used to obtain the complete set of protein-coding
      mitochondrial genes from two rodent taxa. Thanks to the next generation
      sequencing (NGS) 454 approach, we determined the complete mitochondrial DNA
      genome from Graphiurus kelleni (Mammalia: Rodentia: Gliridae) and partial
      mitogenome from Pedetes capensis (Pedetidae), and compared them with published
      rodent and outgroup mitogenomes. We finished the mitogenome sequencing by a
      series of amplicons using conserved PCR primers to fill the gaps corresponding to
      tRNA, rRNA and control regions. Phylogenetic analyses of the mitogenomes suggest
      a well-supported rodent phylogeny in agreement with nuclear gene trees. Pedetes
      groups with Anomalurus into the clade Anomaluromorpha, while Graphiurus branches
      within the squirrel-related clade. Moreover, Pedetes+Anomalurus branch with
      Castor into the mouse-related clade. Our study demonstrates the utility of NGS
      for obtaining new mitochondrial genomes as well as the importance of choosing
      adequate models of sequence evolution to infer the phylogeny of rodents.

PMID- 23973723
TI  - A prenatally ascertained, maternally inherited 14.8 Mb duplication of chromosomal
      bands Xq13.2-q21.31 associated with multiple congenital abnormalities in a male
      fetus.
AB  - Duplications of the X chromosome are rare cytogenetic findings, and have been
      associated with an abnormal phenotype in the male offspring of apparently normal
      or near normal female carriers. We report on the prenatal diagnosis of a
      duplication on the long arm of chromosome X from chromosomal band Xq13.2 to
      q21.31 in a male fetus with increased nuchal translucency in the first trimester
      and polyhydramnios at 22 weeks of gestation. Amniocentesis was undertaken and
      cytogenetic analysis revealed additional chromosomal material in the long arm of
      chromosome X at position Xq13. Analysis with high resolution array CGH revealed
      the additional material is in fact a duplication of the region Xq13.2-q21.13. The
      duplication is 14.8 Mb in size and includes fourteen genes: SLC16A2, KIAA2022,
      ABCB7, ZDHHC15, ATRX, MAGT1, ATP7A, PGK1, TBX22, BRWD3, POU3F4, ZNF711, POF1B and
      CHM. Analysis of the parents revealed the mother to be a carrier of the same
      duplication. After elected termination of the pregnancy at 28 weeks a detailed
      autopsy of the fetus allowed for genotype-phenotype correlations.

PMID- 23973724
TI  - Common MEFV gene mutations in Turkish patients with Behcet's disease.
AB  - Behcet's disease (BD) is a chronic systemic inflammatory disorder whose etiology
      has not been fully established yet. The MEditerranean FeVer (MEFV) gene has been
      identified as the cause of Familial Mediterranean Fever (FMF). BD shows
      similarities with FMF, in terms of clinical findings and treatments, as well as
      their geographical and ethnic co-occurrence. In this study we investigated common
      MEFV gene mutation frequencies in Turkish patients with BD in an area of Turkey
      where both diseases are frequently encountered. We screened 207 BD patients who
      had no symptoms and family history for FMF and 200 healthy subjects for five
      common MEFV gene mutations (E148Q, M680I, M694V, V726A, P369S) and clinical
      features. Seventy-five patients were found to carry a single MEFV mutation, and
      six patients were compound heterozygous. The difference in the frequency of the
      MEFV mutation between the BD and control groups was statistically significant
      (p<0.001, odds ratio [OR] 2.74, 95% confidence interval [CI] 1.75-4.29). The
      frequencies of E148Q and M680I mutations were significantly higher in the BD
      group (p=0.001, p=0.046, respectively). The frequency of uveitis was
      significantly lower in patients with the mutation than in patients without the
      mutation (p=0.029, OR 0.54, 95% CI 0.30-0.98). There was no statistical
      significance between carriers and non-carriers with respect to gender and other
      manifestations of BD. The frequency of the MEFV mutation was significantly higher
      in patients with BD compared to the healthy control group. Based on our results,
      MEFV mutations appear to have a role in the pathogenesis of BD.

PMID- 23973725
TI  - Comparative genomics of four Liliales families inferred from the complete
      chloroplast genome sequence of Veratrum patulum O. Loes. (Melanthiaceae).
AB  - The sequence of the chloroplast genome, which is inherited maternally, contains
      useful information for many scientific fields such as plant systematics,
      biogeography and biotechnology because its characteristics are highly conserved
      among species. There is an increase in chloroplast genomes of angiosperms that
      have been sequenced in recent years. In this study, the nucleotide sequence of
      the chloroplast genome (cpDNA) of Veratrum patulum Loes. (Melanthiaceae,
      Liliales) was analyzed completely. The circular double-stranded DNA of 153,699 bp
      consists of two inverted repeat (IR) regions of 26,360 bp each, a large single
      copy of 83,372 bp, and a small single copy of 17,607 bp. This plastome contains
      81 protein-coding genes, 30 distinct tRNA and four genes of rRNA. In addition,
      there are six hypothetical coding regions (ycf1, ycf2, ycf3, ycf4, ycf15 and
      ycf68) and two open reading frames (ORF42 and ORF56), which are also found in the
      chloroplast genomes of the other species. The gene orders and gene contents of
      the V. patulum plastid genome are similar to that of Smilax china, Lilium
      longiflorum and Alstroemeria aurea, members of the Smilacaceae, Liliaceae and
      Alstroemeriaceae (Liliales), respectively. However, the loss rps16 exon 2 in V.
      patulum results in the difference in the large single copy regions in comparison
      with other species. The base substitution rate is quite similar among genes of
      these species. Additionally, the base substitution rate of inverted repeat region
      was smaller than that of single copy regions in all observed species of Liliales.
      The IR regions were expanded to trnH_GUG in V. patulum, a part of rps19 in L.
      longiflorum and A. aurea, and whole sequence of rps19 in S. china. Furthermore,
      the IGS lengths of rbcL-accD-psaI region were variable among Liliales species,
      suggesting that this region might be a hotspot of indel events and the
      informative site for phylogenetic studies in Liliales. In general, the whole
      chloroplast genome of V. patulum, a potential medicinal plant, will contribute to
      research on the genetic applications of this genus.

PMID- 23973726
TI  - Neurologically normal development of a patient with severe methionine
      adenosyltransferase I/III deficiency after continuing dietary methionine
      restriction.
AB  - BACKGROUND: There is not much information on established standard therapy for
      patients with severe methionine adenosyltransferase (MAT) I/III deficiency. CASE
      PRESENTATION: We report a boy with MAT I/III deficiency, in whom plasma
      methionine and total homocysteine, and urinary homocystine were elevated.
      Molecular genetic studies showed him to have novel compound heterozygous
      mutations of the MAT1A gene: c.191T>A (p.M64K) and c.589delC (p.P197LfsX26). A
      low methionine milk diet was started at 31 days of age, and during continuing
      dietary methionine restriction plasma methionine levels have been maintained at
      less than 750 MUmol/L. He is now 5 years old, and has had entirely normal
      physical growth and psychomotor development. CONCLUSIONS: Although some severely
      MAT I/III deficient patients have developed neurologic abnormalities, we report
      here the case of a boy who has remained neurologically and otherwise normal for 5
      years during methionine restriction, suggesting that perhaps such management,
      started in early infancy, may help prevent neurological complications.

PMID- 23973728
TI  - Molecular defects identified by whole exome sequencing in a child with Fanconi
      anemia.
AB  - Fanconi anemia is a rare genetic disease characterized by bone marrow failure,
      multiple congenital malformations, and an increased susceptibility to malignancy.
      At least 15 genes have been identified that are involved in the pathogenesis of
      Fanconi anemia. However, it is still a challenge to assign the complementation
      group and to characterize the molecular defects in patients with Fanconi anemia.
      In the current study, whole exome sequencing was used to identify the affected
      gene(s) in a boy with Fanconi anemia. A recurring, non-synonymous mutation was
      found (c.3971C>T, p.P1324L) as well as a novel frameshift mutation (c.989_995del,
      p.H330LfsX2) in FANCA gene. Our results indicate that whole exome sequencing may
      be useful in clinical settings for rapid identification of disease-causing
      mutations in rare genetic disorders such as Fanconi anemia.

PMID- 23973727
TI  - Variants of NLRP3 gene are associated with insulin resistance in Chinese Han
      population with type-2 diabetes.
AB  - AIMS: Nod like receptor pyrin domain containing 3 (NLRP3) is the best
      characterized member of nod like receptor family. Recent studies suggest that
      NLRP3 plays a crucial role in the pathogenesis of type-2 diabetes (T2DM), and
      variants in NLRP3 affect its mRNA stability and expression. Therefore, we
      hypothesize that the variants in NLRP3 gene may contribute to T2DM
      susceptibility. The aim of this study is to evaluate the association of NLRP3
      SNPs with T2DM in Chinese Han patients. METHODS: Two common variants in NLRP3
      gene, rs10754558 and rs4612666, were detected using the polymerase chain reaction
      restriction fragment length polymorphism procedure in 952 unrelated T2DM patients
      and 871 healthy controls. All participants were unrelated Chinese Hans. RESULTS:
      The GG genotype and G allele frequencies of rs10754558 were significantly higher
      in T2DM patients than those in controls (for GG genotype, 19.6% vs. 14.5%,
      p=0.019; for G allele, 43.9% vs. 39.8%, p=0.013). The GG genotype of rs10754558
      was significantly associated with higher LDL-C levels and more prone to insulin
      resistance, as evaluated by HOMA-IR or QUICK indexes. CONCLUSIONS: The variant
      (rs10754558) in NLRP3 is related to insulin resistance and increased risk of T2DM
      in Chinese Han population.

PMID- 23973729
TI  - Genetic polymorphisms of xeroderma pigmentosum group D gene Asp312Asn and
      Lys751Gln and susceptibility to prostate cancer: a systematic review and meta
      analysis.
AB  - Many studies have reported the role of xeroderma pigmentosum group D (XPD) with
      prostate cancer risk, but the results remained controversial. To derive a more
      precise estimation of the relationship, a meta-analysis was performed. Odds
      ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the
      association between XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer
      risk. A total of 8 studies including 2620 cases and 3225 controls described
      Asp312Asn genotypes, among which 10 articles involving 3230 cases and 3582
      controls described Lys751Gln genotypes and were also involved in this meta
      analysis. When all the eligible studies were pooled into this meta-analysis, a
      significant association between prostate cancer risk and XPD Asp312Asn
      polymorphism was found. For Asp312Asn polymorphism, in the stratified analysis by
      ethnicity and source of controls, prostate cancer risk was observed in co
      dominant, dominant and recessive models, while no evidence of any associations of
      XPD Lys751Gln polymorphism with prostate cancer was found in the overall or
      subgroup analyses. Our meta-analysis supports that the XPD Asp312Asn polymorphism
      contributed to the risk of prostate cancer from currently available evidence.
      However, a study with a larger sample size is needed to further evaluate gene
      environment interaction on XPD Asp312Asn and Lys751Gln polymorphisms and prostate
      cancer risk.

PMID- 23973730
TI  - Analysis of clinical and laboratory characteristics in 42 patients with
      thrombotic thrombocytopenic purpura from a single center in China.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease
      characterized by microvascular platelet deposition and thrombus formation with
      resulting microangiopathic hemolytic anemia. Deficiency of the von Willebrand
      factor cleavage protease, also known as ADAMTS 13, has been implicated as an
      important etiological factor in TTP. Little studies were obtained on Chinese
      patients with TTP until now. Our aim was to analyze the clinical features,
      outcome and laboratory characteristics of Chinese TTP patients, and determine
      whether plasma ADAMTS 13 activity is decreased in TTP and its diagnostic value
      for TTP. Forty-two TTP patients (29 females; 13 males) admitted to our hospital
      from 1998 to 2010 were analyzed. There were 34 patients (81%) with the triad of
      TTP, including hemolytic anemia, thrombocytopenia and neurologic abnormalities; 7
      (16.7%) had the classical pentad of TTP. Major etiologic factors were acquired
      autoimmunological abnormalities (31%); no familial TTP was identified in this
      series. The schistocytes of peripheral blood smears were present in all cases
      with a mean frequency of 4.6% (range from 0.3% to 13.4%). Plasma ADAMTS 13
      activity was determined in 22 patients with the FRET-vWF86 assay. Only 4
      idiopathic TTP patients (18.2%) had severe ADAMTS 13 deficiency (activity<10%); 9
      (40.9%) had moderate decrease of ADAMTS 13 activity (activity: 10-40%); another 9
      (40.91%) had normal ADAMTS 13 activity (>40%). T lymphocyte subpopulation was
      measured in 23 TTP patients with FACS Calibur; 14 of the 23 (60.9%) had
      significantly decreased CD4 cells count and CD4/CD8 ratio, suggesting cellular
      immune dysfunction may be involved in the pathogenesis of TTP. In the studies,
      plasmapheresis is the main therapeutic method. 26 of 31 patients (83.9%)
      accepting plasmapheresis achieved complete remission; those patients who only
      underwent plasma infusion had low remission rate (18.2%) and high mortality
      (9/11; 81.8%). Four patients with packed RBC infusion manifested transient
      exacerbation of neurologic or psychiatric symptoms. In conclusion, the diagnosis
      of TTP in China is still based on clinical features including evidence of
      microangiopathic hemolysis. Severe ADAMTS 13 activity deficiency might be a
      valuable indicator for idiopathic TTP diagnosis. Further studies are needed to
      determine the real value of ADAMTS 13 activity for TTP diagnosis and whether T
      lymphocytes subset dysregulation plays important role in TTP pathogenesis.

PMID- 23973731
TI  - The costs of mobilisation and collection of peripheral blood stem cells in
      multiple myeloma and lymphoma in an European country: results from The Gruppo
      Italiano Trapianto Midollo Osseo (GITMO) and Societa Italiana di Emaferesi e
      Manipolazione Cellulare (SIdEM) survey.
AB  - Scarce information is available about the cost of mobilisation/collection of
      peripheral blood stem cells for patients undergoing autologous transplant for
      relapsed Lymphoma or Multiple Myeloma. This paper reports the consumption of
      resources and costs collected through a survey among Italian Centres who adhere
      to the GITMO and SIdEM scientific societies. General transplant information was
      extracted from the European Promise database. Resources used alongside the phases
      of mobilisation/collection were retrieved. Resources for each of the process
      phases were quantified and averaged across centres and a unit cost value was
      attributed, based on administrative data from 3 centres, tariffs and market
      values. 25/89 Centres (34% of 2009 Promise transplants) provided data according
      to their standard practice. The mean cost/patient of the process of cell
      mobilisation/collection was ? 6830 +/- 1802 for Multiple Myeloma and ? 7304 +/-
      1542 for Lymphoma. The organisational path for PBSC mobilisation/collection
      appears complex and cumbersome, spread amongst different treatment settings, with
      many different healthcare professionals being involved and considerable amounts
      of time and resources being currently dedicated to the management of patients
      requiring autologous transplantation.

PMID- 23973732
TI  - Separation of the largest eigenvalues in eigenanalysis of genotype data from
      discrete subpopulations.
AB  - We present a mathematical model, and the corresponding mathematical analysis,
      that justifies and quantifies the use of principal component analysis of
      biallelic genetic marker data for a set of individuals to detect the number of
      subpopulations represented in the data. We indicate that the power of the
      technique relies more on the number of individuals genotyped than on the number
      of markers. 

PMID- 23973733
TI  - Meeting report: 26th International Conference on Antiviral Research.
AB  - The 26th International Conference on Antiviral Research (ICAR) was held in San
      Francisco, California from May 11 to 15, 2013. This article summarizes the
      principal invited lectures at the meeting. The opening symposium on the legacy of
      the late Antonin Holy included presentations on his pioneering work with
      nucleotide analogs, which led to the development of several antiviral drugs
      including tenofovir. This drug has transformed the treatment of HIV infection and
      has recently become the first-line therapy for chronic hepatitis B. The Gertrude
      Elion Award lecturer described the anti-HIV activities of the CCR5 inhibitor
      cenicriviroc and the reverse transcriptase inhibitor festinavir(r), and also
      reviewed the evaluation of biodegradable nanoparticles with adjuvant activity.
      The William Prusoff Award winner reported on the creation of NAOMI, a computer
      model with 21 enzymes to predict the activity of nucleoside analogs against
      hepatitis C virus (HCV). Other invited lecturers discussed the development of
      countermeasures against severe dengue and the potential of RNA virus capping and
      repair enzymes as drug targets. Topics in the clinical symposium included the
      current status of the anti-HCV compounds sovaprevir, ACH-3102, miravirsen and ALS
      2200; the evaluation of single-tablet regimens for HIV infection; and the
      investigation of cytomegalovirus resistance to CMX001. Two chemistry minisymposia
      examined strategies and tactics in drug design and the use of in drug discovery. 

PMID- 23973734
TI  - Expression of co-stimulatory molecule B7-H4 in patients suffering from rheumatoid
      arthritis.
AB  - B7-H4, an inhibitory modulator of T-cell response, is one of the most recently
      identified cell surface molecules in the B7-CD28 signaling pathway. However, its
      role in the pathogenesis of rheumatoid arthritis (RA) remains unclear. In the
      present study, the immunofluorescence staining, confocal laser scanning
      microscopy and flow cytometry techniques were used to characterize B7-H4 protein
      expression in RA synovium tissues and peripheral blood mononuclear cell (PBMC)
      subsets, respectively. Our data showed that the immunolocalization of B7-H4 could
      be found on the membrane and in the cytoplasm of synoviocytes and CD19(+) B cells
      in rheumatoid synovium tissues, while B7-H4 was weakly or negatively expressed on
      CD3(+) T cells, CD14(+) monocytes and CD68(+) macrophages. Moreover, B7-H4
      expression was observed in CD34(+) endothelial cells of neovessels in rheumatoid
      synovium. Flow cytometric analysis also showed that positive B7-H4 expression was
      found in CD19(+) B cells and CD14(+) monocytes, but not in CD3(+) T cells. Thus,
      our work identified the expression pattern of B7-H4 in the synovium tissues and
      PBMC subsets from RA patients, suggesting that B7-H4 involves in the pathological
      changes of rheumatoid synovium in RA progression, and its detailed biological
      function needs further investigations. 

PMID- 23973735
TI  - Rapid and sensitive phenotypic marker detection on breast cancer cells using
      surface-enhanced Raman scattering (SERS) imaging.
AB  - We report a surface-enhanced Raman scattering (SERS)-based cellular imaging
      technique to detect and quantify breast cancer phenotypic markers expressed on
      cell surfaces. This technique involves the synthesis of SERS nano tags consisting
      of silica-encapsulated hollow gold nanospheres (SEHGNs) conjugated with specific
      antibodies. Hollow gold nanospheres (HGNs) enhance SERS signal intensity of
      individual particles by localizing surface electromagnetic fields through
      pinholes in the hollow particle structures. This capacity to enhance imaging at
      the level of single molecules permits the use of HGNs to detect specific
      biological markers expressed in living cancer cells. In addition, silica
      encapsulation greatly enhances the stability of nanoparticles. Here we applied a
      SERS-based imaging technique using SEHGNs in the multiplex imaging of three
      breast cancer cell phenotypes. Expression of epidermal growth factor (EGF),
      ErbB2, and insulin-like growth factor-1 (IGF-1) receptors were assessed in the
      MDA-MB-468, KPL4 and SK-BR-3 human breast cancer cell lines. SERS imaging
      technology described here can be used to test the phenotype of a cancer cell and
      quantify proteins expressed on the cell surface simultaneously. Based on results,
      this technique may enable an earlier diagnosis of breast cancer than is currently
      possible and offer guidance in treatment. 

PMID- 23973736
TI  - First detection of Leishmania infantum kinetoplast DNA in hair of wild mammals:
      application of qPCR method to determine potential parasite reservoirs.
AB  - The data presented in this paper describe the application of a method for a
      reliable and non-invasive diagnosis of leishmaniosis in wild reservoirs, based on
      the detection of Leishmania infantum kinetoplast DNA (kDNA) in hair samples by
      Real Time PCR (qPCR). The study has been performed on 68 ear/leg hair samples
      from 5 different wild species (Vulpes vulpes, Canis lupus, Martes foina, Rattus
      norvegicus and Erinaceus europaeus) from several geographic areas of West and
      North Spain. The presence of Leishmania kDNA was detected in 14 of the 68
      analyzed samples, being the highest quantity of DNA observed in foxes. This is
      the first report of the presence of Leishmania in a hedgehog. The kDNA remained
      stable under the exposure of hair to different environmental conditions (freezing
      or high temperature, ultraviolet rays or treatment with tanning salts). This
      detection method could constitute a suitable alternative for the search of the
      parasite in wild hosts, due to the numerous advantages that hair samples present
      for collection, transport and storage processes. 

PMID- 23973737
TI  - Serological surveillance of H5 and H9 avian influenza A viral infections among
      pigs in Southern China.
AB  - Pigs are susceptible to both human and avian influenza viruses (AIV). Moreover,
      they are suspected of being the intermediate hosts or mixing vessels of pandemic
      influenza viruses. Researchers suspect that the influenza viruses are able to
      undergo reassortment or to adapt to various mammalian hosts while they incubate
      in pigs. For the present report, we conducted a serological surveillance of pigs
      in southern China from 2008 to 2012 to establish the prevalence of antibodies
      against H5N1 and H9N2 AIV. A total of one hundred pig farms from the Guangdong,
      Zhejiang, Fujian, and Yunnan Provinces were sampled, yielding a total of 3960
      serum specimens. The haemagglutination inhibition (HI) tests revealed no evidence
      of H5 infection when the Clade 2.3.2 virus was used as the antigen, but a 4.6%
      positive rate of H9 infection was observed when using the Beijing/1/94-like virus
      as the antigen. The positive sera for H9 infection were further verified with
      neutralization tests, which confirmed a 3.7% rate of positive sera of H9
      infection. In summary, the results imply that the swine populations in southern
      China had not been affected greatly by the H5N1 avian influenza virus.
      Nevertheless, these swine H9N2 influenza viruses might pose a threat to human
      health, and so researchers should continue to carry out swine influenza virus
      surveillance in China. 

PMID- 23973738
TI  - Oxygen biosensor based on bilirubin oxidase immobilized on a nanostructured gold
      electrode.
AB  - Gold disk electrodes modified with gold nanoparticles have been used as a
      scaffold for the covalent immobilization of bilirubin oxidase. The nanostructured
      bioelectrodes were tested as mediator-less biosensors for oxygen in a buffer that
      mimics the content and the composition of human physiological fluids.
      Chronoamperometry measurements showed a detection limit towards oxygen of 6 +/- 1
      MUM with a linear range of 6-300 MUM, i.e. exceeding usual physiological ranges
      of oxygen in human tissues and fluids. The biosensor presented is the first ever
      reported oxygen amperometric biosensor based on direct electron transfer of
      bilirubin oxidase.

PMID- 23973739
TI  - Schistosoma japonicum: Tsunagi/Y14 protein plays a critical role in the
      development of the reproductive organs and eggs.
AB  - Tsunagi/Y14 is an evolutionarily conserved RNA-binding protein that is required
      for the maintenance of oogenesis and the masculinization of the germ-line in many
      animal models. We speculated that Tsunagi/Y14 might also regulate reproductive
      organ development in Schistosoma japonicum (S. japonicum, Sj). Sj Tsunagi/Y14 and
      control double-stranded RNAs were introduced into schistosomula by
      electroporation respectively. These transfected schistosomula were cultured in
      vitro for 1, 3 or 5 days. The mRNA and protein levels of the target gene in the
      cultured schistosomula were significantly suppressed compared with those of the
      control group. Furthermore, BALB/c mice were infected with the transfected
      schistosomula for 6 weeks and were sacrificed to harvest the adult worms. We
      found that the silencing of Sj Tsunagi/Y14 led to defects in reproductive organs
      development in both male and female worms. Moreover, it also affected the size,
      quantity and activity of the eggs in the mice liver. Our findings indicated that
      Tsunagi/Y14 plays a critical role in the development of reproductive organs and
      eggs in S. japonicum.

PMID- 23973740
TI  - A new system to measure and compare hepatitis C virus replication capacity using
      full-length, replication competent viruses.
AB  - Measuring the in vitro replication capacity of viruses is an important tool for
      assessing the effects of selective pressure of immune responses and drug therapy.
      Measuring hepatitis C virus (HCV) replication capacity utilizing primarily sub
      genomic reporter constructs is limited. To overcome some of these limitations a
      quantitative reverse transcriptase PCR (RT-qPCR) was designed to measure
      simultaneously the growth rate of 2 whole genome HCV variants under identical
      culture conditions. The assay demonstrates 100% specificity of detection of each
      variant and a linear detection range from 200 to 2*10(8) copies. The system was
      validated using a panel of HCV mutants, including the NS3 protease inhibitor drug
      resistance mutants R155K and T54A. The creation of a unique sequence tag results
      in highly sensitive and specific discrimination of parental JFH-FNX and modified
      clones using distinct probes in a RT-qPCR allowing for comparison of the effect
      of drug resistance or immune escape mutations on HCV replication. This system has
      advantages over existing methods both by permitting direct comparison of the
      replication capacity of fully replication-competent HCV mutants under identical
      culture conditions and by measuring effects on replication capacity due to
      mutations affecting all stages of the viral life cycle including entry and
      egress. 

PMID- 23973742
TI  - Exposure therapy for emetophobia: a case study with three-year follow-up.
AB  - Emetophobia, also referred to as a specific phobia of vomiting, is a largely
      under-researched and poorly understood disorder with prevalence estimates of
      ranging between 1.7 and 3.1% for men and 6 and 7% for women (Hunter & Antony,
      2009; Philips, 1985). The current case study, therefore, sought to methodically
      apply exposure-based behavioral treatment to the treatment of a 26 year-old,
      Hispanic, female suffering from emetophobia. Although not as powerful as a
      randomized design, this description may still add to the existing emetophobia
      literature through the illustration of adaptation of published behavioral
      treatments for other specific phobias. The case presented was successful in terms
      of outcome, and includes a three-year follow up wherein treatment gains were
      measurably maintained. 

PMID- 23973741
TI  - The production, characterisation and application of monoclonal antibodies
      generated by immunisation with HIV-1C clade RGP140 envelope protein.
AB  - The native HIV-1 envelope spike exists as trimers on the virion surface.
      Therefore antibodies elicited following immunisation with trimeric envelope
      vaccines may be directed against epitopes found on functional envelope spikes.
      Novel monoclonal antibodies were produced by priming mice with plasmid DNA
      expressing either HIV-1 CN54 or ZM96 gp140 sequences, and boosting with CN54
      trimeric rgp140. Spleen cells were fused with NS-0 cells and hybridomas were
      screened for production of antibodies which bound trimeric rgp140. 18 monoclonal
      antibodies (MAbs) were isolated from 16 colonies, which were characterised by
      binding in ELISA and Western blotting, neutralisation of pseudotyped viruses and
      isotype. Specificity for the third variable (V3) region was detected in 5 of
      these antibodies, suggesting that the trimeric protein did not alter the main
      focus of the response compared with monomeric protein. 3 MAbs were identified as
      neutralising in a pseudotype assay, all of which were mapped to the V3 region.
      Although cross clade binding of antibodies was detected the neutralisation was C
      clade specific. 

PMID- 23973743
TI  - Just to be certain: Confirming the factor structure of the intolerance of
      uncertainty scale in patients with obsessive-compulsive disorder.
AB  - Intolerance of uncertainty (IU) is a cognitive construct in obsessive-compulsive
      disorder (OCD); yet no studies exist confirming the factor structure of the most
      widely used measure of IU, the intolerance of uncertainty scale (IUS), in OCD
      patients. Moreover, no studies have examined how scores on this measure relate to
      OCD symptom dimensions. Accordingly, the present study examined a 12-item two
      factor revised version of the IUS (IUS-12) in 205 OCD patients. Confirmatory
      factor analysis verified the scale's two-factor structure. The measure also
      demonstrated high internal consistency and the IUS-12 was correlated moderately
      with another self-report measure of IU. Finally, theoretically consistent and
      specific relationships emerged between the IUS-12 and OCD symptom dimensions.
      These findings are discussed in terms of implications for the assessment and
      treatment of OCD, and specifically how elevated scores on the IUS-12 subscales
      may be utilized to identify subtleties in the presentation of OCD-related
      problems with IU.

PMID- 23973744
TI  - Drug dealers: $20 trillion of in-licensing payments.
AB  - To help understand the trends of in-licensing, we analysed 781 in-licensing deals
      costing over $20 trillion over a period of 17 years and found that, while the
      number of FDA approvals is decreasing, the upfront price paid for drug in
      licensing is increasing. Moreover, these upfront payments were not immune to the
      recent economic downturn, where the yearly increase in upfront payments halted in
      years 2008-2012. The cost of buying drugs also steadily increased from early
      research compounds to Phase III drugs. A relative decrease in upfront payments in
      Filed phase versus to Phase III was seen, which may reflect reluctance in buying
      filed drugs that are facing the 'patent cliff'. The data here also showed no
      obvious difference in upfront payments made in five major disease areas, namely,
      oncology, cardiovascular disease, autoimmunity, nervous system and metabolic
      disorders. 

PMID- 23973745
TI  - Biosynthesis of linoleic acid in Tyrophagus mites (Acarina: Acaridae).
AB  - We report here that Tyrophagus similis and Tyrophagus putrescentiae (Astigmata:
      Acaridae) have the ability to biosynthesize linoleic acid [(9Z, 12Z)-9, 12
      octadecadienoic acid] via a Delta12-desaturation step, although animals in
      general and vertebrates in particular appear to lack this ability. When the mites
      were fed on dried yeast enriched with d31-hexadecanoic acid (16:0), d27
      octadecadienoic acid (18:2), produced from d31-hexadecanoic acid through
      elongation and desaturation reactions, was identified as a major fatty acid
      component of phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs) in
      the mites. The double bond position of d27-octadecadienoic acid (18:2) of PCs and
      PEs was determined to be 9 and 12, respectively by dimethyldisulfide (DMDS)
      derivatization. Furthermore, the GC/MS retention time of methyl 9, 12
      octadecadienoate obtained from mite extracts agreed well with those of authentic
      linoleic acid methyl ester. It is still unclear whether the mites themselves or
      symbiotic microorganisms are responsible for inserting a double bond into the
      Delta12 position of octadecanoic acid. However, we present here the unique
      metabolism of fatty acids in the mites. 

PMID- 23973746
TI  - Serum nicotinamide adenine dinucleotide levels through disease course in multiple
      sclerosis.
AB  - The levels of the essential pyridine nucleotide, NAD(+) and its reduced form NADH
      have not been documented in MS patients. We aimed to investigate NAD(+) and NADH
      levels in serum in patients with different disease stages and forms of MS. NAD(+)
      and NADH levels were measured in the serum from 209 patients with relapsing
      remitting MS (RRMS), 136 with secondary progressive MS (SPMS), 51 with primary
      progressive MS (PPMS), and 99 healthy controls. All patients were in a clinically
      stable phase. Serum NAD(+) levels declined by at least 50% in patients with MS
      compared to controls (17.9 +/- 3.2 MUg/ml; p=0.0012). Within the MS sub-groups
      NAD(+) levels were higher in RRMS (9.9 +/- 2.9 MUg/ml; p=0.001) compared to PPMS
      (6.3 +/- 2.1 MUg/ml; p=0.003) and SPMS (7.8 +/- 2.0 MUg/ml; p=0.005). A two-fold
      increase in NADH levels (p=0.002) and at least three-fold reduction in the
      NAD(+)/NADH ratio (p=0.009) were observed in MS patients compared to controls.
      Serum NAD(+) and NADH levels are may be associated with disease progression in
      MS. Given the importance of NAD(+) in the maintenance of normal cellular
      function, it is likely that this molecule is of therapeutic relevance in MS.

PMID- 23973747
TI  - RhoA activity and post-ischemic inflammation in an experimental model of adult
      rodent anterior ischemic optic neuropathy.
AB  - Activation of inflammatory cells and the RhoA signaling pathway may contribute to
      optic nerve damage following non-arteritic anterior ischemic optic neuropathy
      (NAION). We induced an optic nerve infarct with a photothrombotic mechanism in a
      rat model of AION (rAION). Immunohistochemistry and Western blot were performed
      to detect activation of RhoA signaling and inflammation. The extent of Rho
      activity, inflammation, retinal ganglion cell (RGC) loss and extent of axon
      regeneration were determined at 8 and 14 days after infarct. Eight days after
      stroke, we observed significant inflammation and RhoA activity at the site of
      infarction as well as loss of cells in the RGC layer. RhoA activity had decreased
      and inflammation had decreased at day 14 compared with day 8; however, loss of
      RGCs was greater at 14 days than at 8 days. Stroked eyes showed minor axon
      regeneration around the optic nerve lesion site at both 8 and 14 days. These
      results demonstrate that inflammation and RhoA activation occur in rAION at the
      site of infarction. 

PMID- 23973748
TI  - Physical exercise and environment exploration affect synaptogenesis in adult
      generated neurons in the rat dentate gyrus: possible role of BDNF.
AB  - A brief training in a pool maze, with or without cognitive tasks, modifies the
      synaptogenesis and maturation of newborn neurons in adult rat dentate gyrus.
      These types of trainings have many aspects, including physical activity and
      exploration. Therefore, to evaluate whether physical exercise and environment
      exploration are able to affect synapse formation and the maturation of adult
      generated neurons, GFP-retrovirus infusion was performed on rats which, on the
      fourth day after injection, were housed under running conditions or allowed to
      explore an enriched environment briefly in the absence of exercise for the
      following three days. Afterward, at the end of the trainings,
      electrophysiological and morphological studies were conducted. Considering that
      neurotrophic factors increase after exercise or environment exploration,
      hippocampal BDNF levels and TrkB receptor activation were evaluated. In this
      study, we show that both spontaneous physical activity and enriched environment
      exploration induced synaptogenesis and T-type voltage-dependent Ca(2+) currents
      in very immature neurons. Hippocampal BDNF levels and TrkB receptor activation
      were determined to be increasing following physical activity and exploration. A
      possible contribution of BDNF signaling in mediating the observed effects was
      supported by the use of 7-8-dihydroxyflavone, a selective TrkB agonist, and of
      ANA-12, an inhibitor of TrkB receptors. 

PMID- 23973749
TI  - Neurite regeneration in adult rat retinas exposed to advanced glycation end
      products and regenerative effects of neurotrophin-4.
AB  - The purpose of this study was to determine the effect of low concentrations of
      advanced glycation end-products on neurite regeneration in isolated rat retinas,
      and to determine the effects of neurotrophin-4 on regeneration in advanced
      glycation end-products exposed retinas. Retinal explants of 4 adult Sprague
      Dawley rats were cultured on collagen gel and were incubated in; (1) serum-free
      control culture media, (2) glucose-advanced glycation end-products-bovine serum
      albumin media, (3) glycolaldehyde-advanced glycation end-products-bovine serum
      albumin media, (4) glyceraldehyde-advanced glycation end-products-bovine serum
      albumin media, (5) glucose-advanced glycation end-products+neurotrophin-4 media,
      (6) glycolaldehyde-advanced glycation end-products+neurotrophin-4 media, or (7)
      glyceraldehyde-advanced glycation end-products+neurotrophin-4 supplemented
      culture media. After 7 days, the number of regenerating neurites from the
      explants was counted. Then, explants were fixed, cryosectioned, and stained for
      TUNEL. The ratio of TUNEL-positive cells to all cells in the ganglion cell layer
      was determined. Immunohistochemical examinations for the active-form of caspase-9
      and apoptosis-inducing factor were performed. In retinas incubated with advanced
      glycation end-products containing media, the number of regenerating neurites were
      fewer than in retinas without advanced glycation end-products, and the number of
      TUNEL-positive cells and caspase-9- and apoptosis-inducing factor-immunopositive
      cells was significantly higher than in control media. Neurotrophin-4
      supplementation increased the numbers of regenerating neuritis, and the number of
      TUNEL-positives, caspase-9-, and apoptosis-inducing factor-immunopositive cells
      were significantly fewer than that in advanced glycation end-products without
      neurotrophin-4 media. Low doses of advanced glycation end-products impede neurite
      regeneration in the rat retinas. Neurotrophin-4 significantly enhances neurite
      regeneration in retinas exposed to advanced glycation end-products. 

PMID- 23973750
TI  - Attitudes of emergency medicine physicians towards family presence during
      resuscitation.

PMID- 23973751
TI  - Cognitive-motor interference during functional mobility after stroke: state of
      the science and implications for future research.
AB  - Cognitive-motor interference (CMI) is evident when simultaneous performance of a
      cognitive task and a motor task results in deterioration in performance in one or
      both of the tasks, relative to performance of each task separately. The purpose
      of this review is to present a framework for categorizing patterns of CMI and to
      examine the specific patterns of CMI evident in published studies comparing
      single-task and dual-task performance of cognitive and motor tasks during gait
      and balance activities after stroke. We also examine the literature for
      associations between patterns of CMI and a history of falls, as well as evidence
      for the effects of rehabilitation on CMI after stroke. Overall, this review
      suggests that during gait activities with an added cognitive task, people with
      stroke are likely to demonstrate significant decrements in motor performance only
      (cognitive-related motor interference), or decrements in both motor and cognitive
      performance (mutual interference). In contrast, patterns of CMI were variable
      among studies examining balance activities. Comparing people poststroke with and
      without a history of falls, patterns and magnitude of CMI were similar for
      fallers and nonfallers. Longitudinal studies suggest that conventional
      rehabilitation has minimal effects on CMI during gait or balance activities.
      However, early-phase pilot studies suggest that dual-task interventions may
      reduce CMI during gait performance in community-dwelling stroke survivors. It is
      our hope that this innovative and critical examination of the existing literature
      will highlight the limitations in current experimental designs and inform
      improvements in the design and reporting of dual-task studies in stroke. 

PMID- 23973752
TI  - Cadmium exposure induces vascular injury due to endothelial oxidative stress: the
      role of local angiotensin II and COX-2.
AB  - Cadmium is an environmental pollutant that is closely linked with cardiovascular
      diseases, such as atherosclerosis and hypertension. Moreover, cadmium can induce
      an increase in oxidative stress. One of the main sites affected by oxidative
      stress is the aorta, which consequently develops atherosclerosis. However, there
      are few reports demonstrating aortic effects induced by small concentrations of
      cadmium that are similar to those found in the blood resulting from occupational
      exposure. Furthermore, several studies have reported on chronic cadmium exposure,
      and the results of these studies may have been influenced by the secondary
      effects induced by this metal, such as hypertension. Therefore, we investigated
      the effects of acute cadmium exposure on the vascular reactivity to phenylephrine
      of aortic rings isolated from male Wistar rats. Cadmium increased phenylephrine
      reactivity without changing the vasorelaxation induced by acetylcholine and
      sodium nitroprusside. Endothelial damage or incubation with L-NAME shifted the
      phenylephrine concentration-response curves leftward in arteries incubated with
      or without cadmium, but the curves were shifted to a lesser degree after cadmium
      incubation. Enalapril, losartan, the nonselective COX inhibitor indomethacin, the
      TXA(2) synthase inhibitor furegrelate, the selective COX-2 inhibitor NS 398, the
      TP receptor antagonist SQ 29.548, the EP1 receptor antagonist SC 19.220,
      superoxide dismutase, and the NADPH oxidase inhibitor apocynin partially reverted
      the cadmium-induced effects on the reactivity to phenylephrine. Cadmium exposure
      increased vasoconstrictor activity by reducing NO bioavailability owing to the
      increased production of ROS by NADPH oxidase. The results of the tested cadmium
      concentration, which is below the reference values, suggest that acute cadmium
      exposure may induce vascular injury through endothelial oxidative stress. These
      data contribute to the evidence indicating that cadmium is a high risk to public
      health. 

PMID- 23973753
TI  - Photogenotoxicity of folic acid.
AB  - Folic acid (FA), also named vitamin B9, is an essential cofactor for the
      synthesis of DNA bases and other biomolecules after bioactivation by
      dihydrofolate reductase (DHFR). FA is photoreactive and has been shown to
      generate DNA modifications when irradiated with UVA (360 nm) in the presence of
      DNA under cell-free conditions. To investigate the relevance of this reaction for
      cells and tissues, we irradiated three different cell lines (KB nasopharyngeal
      carcinoma cells, HaCaT keratinocytes, and a melanoma cell line) in the presence
      of FA and quantified cytotoxicity and DNA damage generation. The results indicate
      that FA is phototoxic and photogenotoxic by two different mechanisms. First,
      extracellular photodecomposition of FA gives rise to the generation of H2O2,
      which causes mostly DNA strand breaks. If this is prevented, e.g., by the
      presence of catalase, DNA damage generated by intracellular FA becomes evident.
      The damage spectrum in this case consists predominantly of oxidatively generated
      purine modifications sensitive to the repair glycosylase Fpg, as characteristic
      for type I photoreactions, and is associated with the formation of micronuclei.
      In KB cells, the DNA damage is strongly enhanced after pretreatment with the DHFR
      inhibitor methotrexate, which prevents the loss of the chromophore associated
      with the intracellular reduction of FA by DHFR. The results indicate that FA is
      photoreactive in cells and gives rise to nuclear DNA damage under irradiation.

PMID- 23973754
TI  - Nano-lipoidal carriers of tretinoin with enhanced percutaneous absorption,
      photostability, biocompatibility and anti-psoriatic activity.
AB  - Tretinoin (TRE) is a widely used retinoid for the topical treatment of acne,
      psoriasis, skin cancer and photoaging. Despite unmatchable efficacy, it is
      associated with several vexatious side effects like marked skin erythema, peeling
      and irritation, eventually leading to poor patient compliance. Its photo
      instability and high lipophilicity also pose challenges in the development of a
      suitable topical product. The present study, therefore, aims to develop
      biocompatible lipid-based nanocarriers of TRE to improve its skin delivery,
      photostability, biocompatibility and pharmacodynamic efficacy. The TRE-loaded
      liposomes, ethosomes, solid lipid nanoparticles (SLNs) and nanostructured lipidic
      carriers (NLCs) were prepared and characterized for micromeritics, surface
      charge, percent drug efficiency and morphology. Bioadhesive hydrogels of the
      developed systems were also evaluated for rheological characterization,
      photostability, ex vivo skin permeation and retention employing porcine skin, and
      anti-psoriatic activity in mouse tail model. Nanoparticulate carriers (SLNs,
      NLCs) offered enhanced photostability, skin transport and anti-psoriatic activity
      vis-a-vis the vesicular carriers (liposomes, ethosomes) and the marketed product.
      However, all the developed nanocarriers were found to be more biocompatible and
      effective than the marketed product. These encouraging findings can guide in
      proper selection of topical carriers among diversity of such available carriers
      systems. 

PMID- 23973755
TI  - Carnitine palmitoyltransferase 1C deficiency causes motor impairment and
      hypoactivity.
AB  - Carnitine palmitoyltransferase 1c (CPT1C), a brain-specific protein localized in
      the endoplasmic reticulum of neurons, is expressed in almost all brain regions,
      but its only known functions to date are involved in the hypothalamic control of
      energy homeostasis and in hippocampus-dependent spatial learning. To identify
      other physiological and behavioral functions of this protein, we performed a
      battery of neurological tests on Cpt1c-deficient mice. The animals showed intact
      autonomic and sensory systems, but some motor disturbances were observed. A more
      detailed study of motor function revealed impaired coordination and gait, severe
      muscle weakness, and reduced daily locomotor activity. Analysis of motor function
      in these mice at ages of 6-24 weeks showed that motor disorders were already
      present in young animals and that impairment increased progressively with age.
      Analysis of CPT1C expression in different motor brain areas during development
      revealed that CPT1C levels were low from birth to postnatal day 10 and then
      rapidly increased peaking at postnatal day 21, which suggests that CPT1C plays a
      relevant role in motor function during and after weaning. As CPT1C is known to
      regulate ceramide levels, we measured these biolipids in different motor areas in
      adult mice. Cerebellar, striatum, and motor cortex extracts from Cpt1c knockout
      mice showed reduced levels of ceramide and its derivative sphingosine when
      compared to wild-type animals. Our results indicate that altered ceramide
      metabolism in motor brain areas induced by Cpt1c deficiency causes progressive
      motor dysfunction from a young age. 

PMID- 23973756
TI  - Acceptability of pandemic A(H1N1) influenza vaccination by Essential Community
      Workers in 2010 Alicante (Spain), perceived seriousness and sources of
      information.
AB  - OBJECTIVE: Describe acceptability of pandemic A(H1N1) influenza vaccination by
      Essential Community Workers (ECWs) from Alicante province (Spain) in January
      2010. Evaluate the correlation with attitudes, beliefs, professional advice and
      information broadcasted by media. METHOD: In this cross-sectional study, face-to
      face interviews were conducted with 742 ECWs to assess their attitudes towards
      vaccination against the pandemic influenza strain. A multivariable regression
      model was made to adjust the Odds Ratios (ORs). RESULTS: Some ECWs reported
      having been vaccinated with seasonal vaccine, 21.5% (95%IC 18.6-24.9); only 15.4%
      (95%IC 12.8-18.4) with the pandemic one. ECWs vaccinated regularly against
      seasonal flu (OR 5.1; 95%IC 2.9-9.1), those who considered pandemic influenza as
      a severe or more serious disease than seasonal flu (OR 3.8; 95%IC 2.1-6.7) and
      those who never had doubts about vaccine safety (OR 3.7; 95%IC2.1-6.7) had a
      better acceptance of pandemic vaccine. Finally, 78.7% (95%IC 75.1-81.4) had
      doubts about pandemic vaccine's effectiveness. CONCLUSION: The vast amount of
      information provided by the media did not seem to be decisive to prevent doubts
      or to improve the acceptability of the vaccine in ECWs. Professional advice
      should be the focus of interest in future influenza vaccination campaigns. These
      results should be taken into account by health authorities.

PMID- 23973757
TI  - Metabolism and tissue distribution study of Vaccaria seeds (Wang-Bu-Liu-Xing) in
      benign prostatic hyperplasia model rat: toward an in-depth study for its
      bioactive components.
AB  - Vaccaria seeds (Wang-Bu-Liu-Xing), a well-known traditional Chinese medicine
      (TCM), has been used as an emperor herb of many ancient formulas to treat benign
      prostatic hyperplasia (BPH) in clinic. However, its metabolism and tissue
      distribution, especially in the target tissue, had not been investigated so far.
      Based on the hypothesis that the components which exert effect against BPH of
      Vaccaria seeds would be measureable in target tissue (prostate), in vivo
      metabolism and tissue distribution of Vaccaria seeds in rats were profiled using
      a specific and sensitive high performance liquid chromatography coupled with
      electrospray ionization quadrupole time-of-flight mass spectrometry (LC-QTOF
      MS/MS). As a result, 19 major constituents in the Vaccaria seeds decoction and 19
      constituents in rat plasma, feces and tissues after oral administration of
      Vaccaria seeds decoction were identified. Accurate mass measurement for molecular
      ions and characteristic fragment ions could represent reliable identification
      criteria for these compounds. Two prototypes were detected in prostate. An in
      vitro metabolism analysis of them was studied after incubation with rat
      intestinal flora and rat liver microsome (RLM) in this paper, which is helpful
      for further investigation of the potential effect of these two components. The
      result of this study provided meaningful information for further pharmacology
      research on Vaccaria seeds. 

PMID- 23973758
TI  - Comparative analysis of two species of Asari Radix et Rhizoma by electronic nose,
      headspace GC-MS and chemometrics.
AB  - Traditional Chinese medicines (TCM) can be identified by experts according to
      their odors. However, the identification of these medicines is subjective and
      requires long-term experience. In this paper, electronic nose, headspace gas
      chromatography-mass spectrometry (GC-MS) and chemometrics methods were applied to
      differentiate two species of Asari Radix et Rhizoma by their odors. The samples
      used were the dried roots and rhizomes of Asarum heterotropoides var.
      mandshuricum (AH) and Asarum sieboldii (AS). The electronic nose was used to
      determine the odors of the samples and enabled rapid differentiation of AH and AS
      when coupled with principal component analysis. Headspace GC-MS was utilized to
      reveal the differences between the volatile constituents of AH and AS. In all, 54
      volatile constituents were identified, and 9 major constituents (eucalyptol,
      eucarvone, 3,5-dimethoxytoluene, 3,4,5-trimethoxytoluene, methyleugenol, 2,3,5
      trimethoxytoluene, croweacin, pentadecane and asaricin) could be used as chemical
      markers to distinguish these two species. AH contained higher relative contents
      of eucarvone (1.79-16.76%), 3,5-dimethoxytoluene (6.64-26.52%), 3,4,5
      trimethoxytoluene/methyleugenol (6.43-31.67%) and 2,3,5-trimethoxytoluene (1.64
      6.66%), whereas AS had higher relative contents of eucalyptol (14.06-24.95%),
      croweacin (5.64-13.55%), pentadecane (8.44-20.82%) and asaricin (7.03-13.45%).
      Moreover, AH and AS could be distinguished according to the contents of either
      all 54 identified volatile constituents or only the 9 major constituents by
      employing cluster analysis. The proposed method is rapid, simple, eco-friendly
      and can successfully differentiate these two species of Asari Radix et Rhizoma by
      their odors. 

PMID- 23973759
TI  - Monodisperse, molecularly imprinted polymers for creatinine by modified
      precipitation polymerization and their applications to creatinine assays for
      human serum and urine.
AB  - Molecularly imprinted polymers (MIPs) for creatinine were prepared by modified
      precipitation polymerization using methacrylic acid as a functional monomer and
      divinylbenzene as a crosslinker. The prepared MIPs were monodispersed with a
      narrow particle size distribution. Binding experiments and Scatchard analyses
      revealed that two classes of binding sites, high- and low-affinity sites, were
      formed on the MIPs. The retention and molecular-recognition properties of the
      MIPs were evaluated by hydrophilic interaction chromatography using a mixture of
      ammonium acetate buffer and acetonitrile as a mobile phase. With an increase of
      acetonitrile content, the retention factor of creatinine was increased on the
      MIP. In addition to shape recognition, hydrophilic interactions seemed to enhance
      the recognition of creatinine on the MIP. The MIPs' molecular-recognition ability
      was specific for creatinine; the structurally related compounds such as
      hydantoin, 1-methylhydantoin, 2-pyrrolidone, N-hydroxysuccinimide and creatine
      were not recognized. Furthermore, the creatinine concentrations in human serum
      and urine were successfully determined by direct injection of the deproteinized
      serum and diluted urine samples onto the MIP. 

PMID- 23973760
TI  - Simultaneous qualitative and quantitative analysis of phenolic acids and
      flavonoids for the quality control of Apocynum venetum L. leaves by HPLC-DAD-ESI
      IT-TOF-MS and HPLC-DAD.
AB  - A reliable method based on high performance liquid chromatography-diode array
      detector-electrospray ionization-ion trap-time of flight-mass spectrometry (HPLC
      DAD-ESI-IT-TOF-MS) was developed for the identification of phenolic acids and
      flavonoids in Apocynum venetum L. leaves and its adulterant, Pocynum hendersonii
      (Hook. f.) Woodson leaves. A total of 21 compounds were identified or tentatively
      identified, including 4 phenolic acids and 17 flavonoids. 3-O-caffeoylquinic acid
      (3-CQA) and caffeic acid were detected for the first time in A. venetum leaves; 4
      O-caffeoylquinic acid (4-CQA), 3-CQA, caffeic acid, quercetin-3-O-(6"-O-malonyl)
      galactoside, quercetin-3-O-(6"-O-malonyl)-glucoside, kaempferol-3-O-(6"-O
      malonyl)-glucoside, kaempferol-3-O-(6"-O-acetyl)-glucoside, and kaempferol-3-O
      dihexoside were detected for the first time in P. hendersonii leaves. Cluster
      analysis was employed to analyze 24 batches of A. venetum leaves and 5 batches of
      P. hendersonii leaves collected from various regions in China. The analysis,
      which was based on the 21 compounds, indicated that profiles of these compounds
      were distinct between the two species, and among A. venetum leaf samples from
      different origins. 18 of these 21 compounds were selected as the markers and
      simultaneously analyzed by HPLC-DAD for the first time. The quantitative
      analytical method was validated and subsequently applied to the comprehensive
      quality evaluation of 24 batches of A. venetum leaves.

PMID- 23973761
TI  - Re: 'Diffuse ganglioneuromatosis and plexiform neurofibroma of the urinary
      bladder: an uncommon cause of severe urological disease in an infant'. J Pediatr
      Urol. 2013 Apr; 9(3):e131-e133.

PMID- 23973762
TI  - Short and long sleep duration and risk of drowsy driving and the role of
      subjective sleep insufficiency.
AB  - Experimental sleep restriction increases sleepiness and impairs driving
      performance. However, it is unclear whether short sleep duration in the general
      population is associated with drowsy driving. The goal of the present study was
      to evaluate whether individuals in the general population who obtained sleep of
      6h or less are more likely to report drowsy driving, and evaluate the role of
      perceived sleep sufficiency. Data exploring whether subgroups of short sleepers
      (those who report the most or least unmet sleep need) show different risk
      profiles for drowsy driving are limited. From the 2009 Behavioral Risk Factor
      Surveillance System (N=31,522), we obtained the following self-reported data: (1)
      sleep duration (<=5, 6, 7, 8, 9, or >=10 h/night); (2) number of days/week of
      perceived insufficient sleep; (3) among drivers, yes/no response to: "During the
      past 30 days, have you ever nodded off or fallen asleep, even just for a brief
      moment, while driving?" (4) demographics, physical/mental health. Using 7 h/night
      as reference, logistic regression analyses evaluated whether self-reported sleep
      duration was associated with drowsy driving. Overall, 3.6% reported drowsy
      driving. Self-identified short-sleepers reported drowsy driving more often, and
      long sleepers, less often. Among those who perceived sleep as always
      insufficient, drowsy driving was reported more often when sleep duration was <=5
      h, 6 h, or >=10 h. Among those who perceived sleep as always sufficient, drowsy
      driving was reported more often among <=5 h and 6h sleepers. Overall, drowsy
      driving was common, particularly in self-identified short-sleepers as a whole, as
      well as subgroups based on sleep insufficiency.

PMID- 23973763
TI  - Social and environmental contexts modulate sleep deprivation-induced c-Fos
      activation in rats.
AB  - People often sleep deprive themselves voluntarily for social and lifestyle
      reasons. Animals also appear to stay awake longer as a result of their natural
      curiosity to explore novel environments and interact socially with conspecifics.
      Although multiple arousal systems in the brain are known to act jointly to
      promote and maintain wakefulness, it remains unclear whether these systems are
      similarly engaged during voluntary vs. forced wakefulness. Using c-Fos
      immunohistochemistry, we compared neuronal responses in rats deprived of sleep
      for 2 h by gentle sensory stimulation, exploration under social isolation, or
      exploration with social interaction, and rats under undisturbed control
      conditions. In many arousal, limbic, and autonomic nuclei examined (e.g.,
      anterior cingulate cortex and locus coeruleus), the two sleep deprivation
      procedures involving exploration were similarly effective, and both were more
      effective than sleep deprivation with sensory stimulation, in increasing the
      number of c-Fos immunoreactive neurons. However, some nuclei (e.g.,
      paraventricular hypothalamic nucleus and select amygdala nuclei) were more
      responsive to exploration with social interaction, while others (e.g.,
      histaminergic tuberomammillary nucleus) responded more strongly to exploration in
      social isolation. In the rostral basal forebrain, cholinergic and GABAergic
      neurons responded preferentially to exploration with social interaction, whereas
      resident neurons in general responded most strongly to exploration without social
      interaction. These results indicate that voluntary exploration with/without
      social interaction is more effective than forced sleep deprivation with gentle
      sensory stimulation for inducing c-Fos in arousal and limbic/autonomic brain
      regions, and suggest that these nuclei participate in different aspects of
      arousal during sustained voluntary wakefulness.

PMID- 23973764
TI  - Sucrose Bobs and Quinine Gapes: horse (Equus caballus) responses to taste support
      phylogenetic similarity in taste reactivity.
AB  - Evidence suggests that behavioural affective reactions to sweet and bitter
      substances are homologous in humans, nonhuman primates, and rodents. The sweet
      taste of sucrose elicits facial responses that include rhythmic tongue
      protrusions whereas the bitter taste of quinine elicits facial responses that
      include gapes, featuring an opening of the mouth and protrusion of the tongue.
      The present study using the horse (Equus caballus) was undertaken for three
      reasons: (1) there is debate about the presence of a sweet receptor gene in the
      horse, (2) there is a need to expand the examination of facial reactions to taste
      in lineages other than the closely related lineages of rodents and primates, and
      (3) the horse provides an opportunity to test the hypothesis that some social
      signals derive from movements related to taste reaction. The horses were given
      oral infusions of either sucrose or quinine and their behaviour was examined
      using frame-by-frame video analysis. Control groups were exposed received water
      or syringe insertion only. Amongst the many responses made to the infusions, the
      distinctive response to sucrose was a bob coupled with a slight tongue protrusion
      and forward movement of the ears; the distinctive response to quinine was a head
      extension and mouth gape accompanied by a large tongue protrusion and backward
      movement of the ears. Sucrose Bobs and Quinine Gapes are discussed with respect
      to: (1) the relevance of facial reactions to both sucrose and quinine to taste
      receptors in horses, (2) the similarity of features of taste expression in horses
      to those documented in rodents and primates, and (3) the dissimilarity between
      facial reactions to taste and other social signals displayed by horses. 

PMID- 23973765
TI  - Stop-signal task difficulty and the right inferior frontal gyrus.
AB  - The stop-signal paradigm is increasingly being used as a probe of response
      inhibition in basic and clinical neuroimaging research. The critical feature of
      this task is that a cued response is countermanded by a secondary 'stop-signal'
      stimulus offset from the first by a 'stop-signal delay'. Here we explored the
      role of task difficulty in the stop-signal task with the hypothesis that what is
      critical for successful inhibition is the time available for stopping, that we
      define as the difference between stop-signal onset and the expected response time
      (approximated by reaction time from previous trial). We also used functional
      magnetic resonance imaging (fMRI) to examine how the time available for stopping
      affects activity in the putative right inferior frontal gyrus and
      presupplementary motor area (right IFG-preSMA) network that is known to support
      stopping. While undergoing fMRI scanning, participants performed a stop-signal
      variant where the time available for stopping was kept approximately constant
      across participants, which enabled us to compare how the time available for
      stopping affected stop-signal task difficulty both within and between subjects.
      Importantly, all behavioural and neuroimaging data were consistent with previous
      findings. We found that the time available for stopping distinguished successful
      from unsuccessful inhibition trials, was independent of stop-signal delay, and
      affected successful inhibition depending upon individual SSRT. We also found that
      right IFG and adjacent anterior insula were more strongly activated during more
      difficult stopping. These findings may have critical implications for stop-signal
      studies that compare different patient or other groups using fixed stop-signal
      delays. 

PMID- 23973766
TI  - Temporal associations for spatial events: the role of the dentate gyrus.
AB  - Previous research suggests that the dorsal dentate gyrus (DG) hippocampal
      subregion mediates spatial processing functions. However, a novel role for the DG
      in temporal processing for spatial information has begun to emerge based on the
      development of a computational model of neurogenesis. According to this model,
      adult born granule cells in the DG contribute to a temporal associative
      integration process for events presented closer in time. Currently, there is a
      paucity of behavioral evidence to support the temporal integration theory.
      Therefore, we developed a novel behavioral paradigm to investigate the role of
      the dDG in temporal integration for proximal and distal spatial events. Male Long
      Evans rats were randomly assigned to a control group or to receive bilateral
      intracranial infusions of colchicine into the dDG. Following recovery from
      surgery, each rat was tested on a cued-recall of sequence paradigm. In this task,
      animals were allowed to explore identical objects placed in designated spatial
      locations on a cheeseboard maze across 2 days (e.g., Day 1: A and B; Day 2: C and
      D). One week later, animals were given a brief cue (A or C) followed by a
      preference test between spatial location B and D. Control animals had a
      significant preference for the spatial location previously paired with the cue
      (the temporal associate) whereas dDG lesioned animals failed to show a
      preference. These findings suggest that selective colchicine-induced dDG lesions
      are capable of disrupting the formation of temporal associations between spatial
      events presented close in time. 

PMID- 23973767
TI  - Use of laser capture microdissection to map hepatitis C virus-positive
      hepatocytes in human liver.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) predominantly infects hepatocytes, but
      many hepatocytes are not infected; studies have shown that HCV antigens cluster
      within the liver. We investigated spatial distribution and determinants of HCV
      replication in human liver samples. METHODS: We analyzed liver samples from 4
      patients with chronic HCV infection (genotype 1, Metavir scores 0-1) to estimate
      the proportion of infected hepatocytes and the amount of HCV viral RNA (vRNA) per
      cell. Single-cell laser capture microdissection was used to capture more than
      1000 hepatocytes in grids, to preserve geometric relationships. HCV vRNA and
      interferon-induced transmembrane protein 3 (IFITM3) messenger RNA (the transcript
      of an interferon-stimulated gene) were measured in the same hepatocytes by
      quantitative polymerase chain reaction and assembled in maps to identify areas of
      high and low HCV replication. RESULTS: Patients' serum levels of HCV RNA ranged
      from 6.87 to 7.40 log10 IU/mL; the proportion of HCV-infected hepatocytes per
      person ranged from 21% to 45%, and the level of vRNA ranged from 1 to 50
      IU/hepatocyte. Infection was not random; we identified clustering of HCV-positive
      hepatocytes using infected-neighbor analysis (P < .0005) and distance to the kth
      nearest neighbor compared with random distributions, obtained by bootstrap
      simulations (P < .02). Hepatocytes that expressed IFITM3 did not appear to
      cluster and were largely HCV negative. CONCLUSIONS: We used single-cell laser
      capture and high-resolution analysis to show that in human liver HCV infects
      hepatocytes in nonrandom clusters, whereas expression of antiviral molecules is
      scattered among hepatocytes. These findings show that quantitative single-cell
      RNA measurements can be used to estimate the abundance of HCV vRNA per infected
      human hepatocyte and are consistent with cell-cell propagation of infection in
      the absence of clustered IFITM3.

PMID- 23973768
TI  - Ascorbic acid and dietary polyphenol combinations protect against genotoxic
      damage induced in mice by endogenous nitrosation.
AB  - We investigated whether combinations of ascorbic acid (AA) plus dietary
      polyphenols can protect in vivo against genotoxic damage induced by endogenous
      nitrosation. A nitrosation reaction mixture consisting of methylurea (MU) plus
      sodium nitrite (SN), which can react to form N-nitroso-N-methylurea in the
      stomach, was administered orally to mice, together with AA and one of the dietary
      polyphenols ferulic acid (FA), gallic acid (GA), chlorogenic acid (CA), or
      epigallocatechin gallate (EGCG). Genotoxic damage in bone marrow cells was
      assessed by measuring micronucleated polychromatic erythrocytes (Mn PCEs) and
      metaphase chromosome aberrations. When compared to damage induced by MU plus SN
      alone, co-administration with AA, FA, GA, CA, or EGCG resulted in significant
      protective effects. Combinations of AA plus EGCG or AA plus CA showed a further
      protective effect. Reduction in the frequency of Mn PCEs to the control level was
      obtained following co-administration of a combination of AA, FA, GA, and CA with
      MU plus SN. A similar trend was observed for metaphase chromosome aberrations. Co
      administration of AA, FA, GA, or CA with N-nitroso-N-methylurea (MNU) did not
      show any significant reduction in genotoxicity, indicating the absence of a
      protective effect against a preformed N-nitroso compound. Our work demonstrates
      the protective effects of the 'antinitrosating' combination of AA and dietary
      polyphenols FA, GA, or CA against genotoxic damage induced by an endogenously
      formed N-nitroso compound. 

PMID- 23973769
TI  - Multiscale damage and strength of lamellar bone modeled by cohesive finite
      elements.
AB  - A computational multiscale model of damage mechanisms and strength of lamellar
      bone is presented. The analysis incorporates the hierarchical structure of bone
      spanning the nanoscale (mineralized collagen fibril), the sub-microscale (single
      lamella) and the microscale (lamellar structure) levels. Due to the presence of
      several constituents (collagen, hydroxyapatite minerals, and non-collagenous
      proteins) and the different microstructural features at each scale, various
      deformation and failure mechanisms occur in bone at its several levels of
      hierarchy. The model takes into account the dominant damage mechanisms at the
      above mentioned three scales and predicts the strength of bone by using a
      cohesive finite element method. Elastic moduli of bone at these three different
      scales are also obtained as part of these calculations. The obtained modeling
      results compare well with other theoretical and experimental data available in
      the literature. 

PMID- 23973770
TI  - Blast effect on the lower extremities and its mitigation: a computational study.
AB  - A series of computational studies were performed to investigate the response of
      the lower extremities of mounted soldiers under landmine detonation. A numerical
      human body model newly developed at Wayne State University was used to simulate
      two types of experimental studies and the model predictions were validated
      against test data in terms of the tibia axial force as well as bone fracture
      pattern. Based on the validated model, the minimum axial force causing tibia
      facture was found. Then a series of parametric studies was conducted to determine
      the critical velocity (peak velocity of the floor plate) causing tibia fracture
      at different upper/lower leg angles. In addition, to limit the load transmission
      through the vehicular floor, two types of energy absorbing materials, namely
      IMPAXX((r)) foam and aluminum alloy honeycomb, were selected for floor matting.
      Their performances in terms of blast effect mitigation were compared using the
      validated numerical model, and it has been found that honeycomb is a more
      efficient material for blast injury prevention under the loading conditions
      studied. 

PMID- 23973773
TI  - Abstracts from the 33rd Annual Conference of the National Academy of
      Neuropsychology, San Diego, California, October 16-19, 2013.

PMID- 23973772
TI  - Tensile and microindentation properties of maxillofacial elastomers after
      different disinfecting procedures.
AB  - STATEMENT OF PROBLEM: Daily disinfection of maxillofacial prosthesis may reduce
      their service-life and lead to replacement. PURPOSE: The purpose of this study
      was to evaluate possible alterations in the mechanical behavior of two
      maxillofacial elastomers after application of four different disinfection
      procedures. MATERIAL AND METHODS: The materials tested were two maxillofacial
      elastomers, a commercially available polydimethylsiloxane (PDMS) and an
      experimental chlorinated polyethylene (CPE). Different disinfection procedures
      such as microwave exposure, hypochlorite solution, neutral soap and a
      commercially antimicrobial solution, were applied for a period which simulates
      one year of a real service life. Mechanical behavior was investigated through
      tensile and microindentation tests in various depths. Mathematical models were
      fitted to tensile curves. Alterations in tensile parameters (maximum stress,
      maximum strain, elasticity and viscoelasticity parameter) were subjected to two
      way ANOVA and Tukey's post hoc tests (alpha=.05). RESULTS: Most of the tensile
      parameters presented significant alterations among different disinfection
      procedures and maxillofacial materials which became also harder. Microwave
      exposure caused greater changes in PDMS and CPE elastomer whereas commercial
      antimicrobial solution and neutral soap did not significantly affect them.
      Microindentation and tensile tests revealed similar changes in materials' elastic
      modulus and hardness whereas the observed changes were greater into smaller
      depths. CONCLUSIONS: Tensile and microindentation properties of PDMS and CPE
      elastomers presented changes after disinfected with four different procedures.
      Changes in the surface of both materials were more intense than in the bulk of
      the materials. Microwave exposure affected most the two elastomers, so concerning
      the findings of this study is not recommended for the disinfection of the
      examined PDMS and CPE elastomers. Moreover, microwave exposure and hypochlorite
      solution caused greater changes in the surface (3MUm) of CPE samples as indicated
      by microindentation results. PDMS affected less from the commercial antimicrobial
      agent and CPE from neutral soap, which seems to be the most suitable disinfection
      techniques.

PMID- 23973771
TI  - Computational and experimental study of the mechanics of embryonic wound healing.
AB  - Wounds in the embryo show a remarkable ability to heal quickly without leaving a
      scar. Previous studies have found that an actomyosin ring (purse string) forms
      around the wound perimeter and contracts to close the wound over the course of
      several dozens of minutes. Here, we report experiments that reveal an even faster
      mechanism which remarkably closes wounds by more than 50% within the first 30s.
      Circular and elliptical wounds (~100MUm in size) were made in the blastoderm of
      early chick embryos and allowed to heal, with wound area and shape characterized
      as functions of time. The closure rate displayed a biphasic behavior, with rapid
      constriction lasting about a minute, followed by a period of more gradual closure
      to complete healing. Fluorescent staining suggests that both healing phases are
      driven by actomyosin contraction, with relatively rapid contraction of fibers at
      cell borders within a relatively thick ring of tissue (several cells wide) around
      the wound followed by slower contraction of a thin supracellular actomyosin ring
      along the margin, consistent with a purse string mechanism. Finite-element
      modeling showed that this idea is biophysically plausible, with relatively
      isotropic contraction within the thick ring giving way to tangential contraction
      in the thin ring. In addition, consistent with experimental results, simulated
      elliptical wounds heal with little change in aspect ratio, and decreased membrane
      tension can cause these wounds to open briefly before going on to heal. These
      results provide new insight into the healing mechanism in embryonic epithelia. 

PMID- 23973778
TI  - Antiproliferative effect of alkylglycerols as vehicles of butyric acid on colon
      cancer cells.
AB  - The anticarcinogenic activity of synthetic 1-O-octadecyl-2,3-dibutyroilglycerol
      (D-SCAKG) in tumor-cell line of colonocytes (SW620) was performed. The effect of
      the previously digested D-SCAKG under in vitro intestinal conditions was compared
      to the bioactivity of non-digested D-SCAKG. Antiproliferative activity of each
      individual product from digestion (1-O-octadecyl-2-butyroilglycerol; 1-O
      octadecyl glycerol; butyric acid) was also performed. The impact of
      solubilization of lipid products within micellar structures was also tested. The
      1-O-octadecyl glycerol was the most active compound, followed by 1-O-octadecyl-2
      butyroilglycerol, D-SCAKG and butyric acid. The 1-O-octadecyl glycerol and
      butyric acid were the only molecules that showed antiproliferative effect in
      absence of micelles. Digested D-SCAKG was 4-fold more effective than non-digested
      D-SCAKG. A synergism between 1-O-octadecyl-2-butyroilglycerol and 1-O-octadecyl
      glycerol was evidenced. As summary, the synthetic D-SCAKG seems to be an
      interesting antitumoral lipid against colonocytes, especially after previous
      intestinal digestion, and mainly due to the synergism of the major products,
      namely 1-O-octadecyl-2-butyroilglycerol and 1-O-octadecyl glycerol. At the same
      time, 1-O-octadecyl-2-butyroilglycerol would constitute a stable esterified form
      of butyric acid for its vehiculization.

PMID- 23973779
TI  - The effect of micro-environment on luminescence of aequorin: the role of amino
      acids and explicit water molecules on spectroscopic properties of coelenteramide.
AB  - Despite the fact that the luminescence reaction mechanism of aequorin has been
      intensively investigated, details in luminescence such as the effect of important
      amino acids residues and explicit water molecules on spectroscopic properties of
      coelenteramide remain unclear. In this work, the effect of amino acids residues
      His16, Tyr82, Trp86, Phe113, Trp129, Tyr132, explicit water molecules Wat505 and
      Wat405 on the spectral properties of CLM(-) has been studied by CAM-B3LYP, TD
      M06L and TD CAM-B3LYP methods in hydrophobic environment and aqueous solution. In
      hydrophobic environment, the amino acids or water molecules have no significant
      effect on the absorption. Tyr82 and Trp86 move close to CLM(-) changes the
      hydrogen bond network, and thus, the spectral properties is significantly
      affected by the hydrogen bonds between His16H(+)+Tyr82+Trp86 and CLM(-). Tyr82,
      Trp86 hydrogen bonding to CLM(-) upshifts the excited energy and helps emission
      spectra shift to blue region. Therefore, it is concluded that
      His16H(+)+Tyr82+Trp86 modify the emission spectra. The molecular electrostatic
      potential indicated that the greater electron density is located at the oxygen
      atom of 6-p-hydroxyphenyl group of CLM(-), and it facilitates the formation of
      hydrogen bond with His16H(+)+Tyr82+Trp86. It is a critical condition for the
      modification of emission spectra. It is expected to help to understand the
      interactions between emitter and amino acids in the micro environment. 

PMID- 23973780
TI  - A combined spectroscopic, molecular docking and molecular dynamic simulation
      study on the interaction of quercetin with beta-casein nanoparticles.
AB  - The interaction of quercetin with beta-casein nanoparticle micelle was studied at
      various temperatures in order to do a complete thermodynamic and molecular
      analysis on the binding process. The results of fluorescence studies showed the
      possibility of fluorescence energy transfer between excited tryptophan and
      quercetin. The determined values of critical transfers distance and the mean
      distance of ligand from Trp-143 residues in beta-casein micelle represents a non
      radiative energy transfer mechanism for quenching and the existence of a
      significant interaction between this flavonoid and beta-casein nanoparticle. The
      equilibrium binding of quercetin with beta-casein micelle at different
      temperatures was studied by using UV-Vis absorption spectroscopy. The chemometric
      analysis (principal component analysis (PCA) and multivariate curve resolution
      alternating least squares (MCR-ALS) methods) on spectrophotometric data revealed
      the existence of two components in solution (quercetin and beta-casein-quercetin
      complex) and resolved their pure concentration and spectral profiles. This
      information let us to calculate the equilibrium binding constant at various
      temperatures and the relevant thermodynamic parameters of interaction (enthalpy,
      entropy and Gibbs free energy) with low uncertainty. The negative values of
      entropy and enthalpy changes represent the predominate role of hydrogen binding
      and van der Waals interactions in the binding process. Docking calculations
      showed the probable binding site of quercetin is located in the hydrophobic core
      of beta-casein where the quercetin molecule is lined by hydrophobic residues and
      make five hydrogen bonds and several van der Waals contacts with them. Moreover,
      molecular dynamic (MD) simulation results suggested that this flavonoid can
      interact with beta-casein, without affecting the secondary structure of beta
      casein. Simulations, molecular docking and experimental data reciprocally
      supported each other. 

PMID- 23973781
TI  - 2nd congress on steroid research.

PMID- 23973782
TI  - Special issue on pregnancy and steroids: editorial.

PMID- 23973783
TI  - Classifying G-protein-coupled receptors to the finest subtype level.
AB  - G-protein-coupled receptors (GPCRs) constitute a remarkable protein family of
      receptors that are involved in a broad range of biological processes. A large
      number of clinically used drugs elicit their biological effect via a GPCR. Thus,
      developing a reliable computational method for predicting the functional roles of
      GPCRs would be very useful in the pharmaceutical industry. Nowadays, researchers
      are more interested in functional roles of GPCRs at the finest subtype level.
      However, with the accumulation of many new protein sequences, none of the
      existing methods can completely classify these GPCRs to their finest subtype
      level. In this paper, a pioneer work was performed trying to resolve this problem
      by using a hierarchical classification method. The first level determines whether
      a query protein is a GPCR or a non-GPCR. If it is considered as a GPCR, it will
      be finally classified to its finest subtype level. GPCRs are characterized by 170
      sequence-derived features encapsulating both amino acid composition and
      physicochemical features of proteins, and support vector machines are used as the
      classification engine. To test the performance of the present method, a non
      redundant dataset was built which are organized at seven levels and covers more
      functional classes of GPCRs than existing datasets. The number of protein
      sequences in each level is 5956, 2978, 8079, 8680, 6477, 1580 and 214,
      respectively. By 5-fold cross-validation test, the overall accuracy of 99.56%,
      93.96%, 82.81%, 85.93%, 94.1%, 95.38% and 92.06% were observed at each level.
      When compared with some previous methods, the present method achieved a
      consistently higher overall accuracy. The results demonstrate the power and
      effectiveness of the proposed method to accomplish the classification of GPCRs to
      the finest subtype level. 

PMID- 23973784
TI  - Potent inhibition of L-type Ca2+ currents by a Rad variant associated with
      congestive heart failure.
AB  - Ca(2+) influx via L-type voltage-gated Ca(2+) channels supports the plateau phase
      of ventricular action potentials and is the trigger for excitation-contraction
      (EC) coupling in the myocardium. Rad, a member of the RGK (Rem, Rem2, Rad,
      Gem/Kir) family of monomeric G proteins, regulates ventricular action potential
      duration and EC coupling gain through its ability to inhibit cardiac L-type
      channel activity. In this study, we have investigated the potential dysfunction
      of a naturally occurring Rad variant (Q66P) that has been associated with
      congestive heart failure in humans. Specifically, we have tested whether Rad Q66P
      limits, or even eliminates, the inhibitory actions of Rad on CaV1.2 and CaV1.3,
      the two L-type channel isoforms known to be expressed in the heart. We have found
      that mouse Rad Q65P (the murine equivalent of human Rad Q66P) inhibits L-type
      currents conducted by CaV1.2 or CaV1.3 channels as potently as wild-type Rad
      (>95% inhibition of both channels). In addition, Rad Q65P attenuates the gating
      movement of both channels as effectively as wild-type Rad, indicating that the
      Q65P substitution does not differentially impair any of the three described modes
      of L-type channel inhibition by RGK proteins. Thus, we conclude that if Rad Q66P
      contributes to cardiomyopathy, it does so via a mechanism that is not related to
      its ability to inhibit L-type channel-dependent processes per se. However, our
      results do not rule out the possibility that decreased expression, mistargeting
      or altered regulation of Rad Q66P may reduce the RGK protein's efficacy in vivo. 

PMID- 23973785
TI  - Development and validation of a multiplex quantitative PCR assay for the rapid
      detection of Grapevine virus A, B and D.
AB  - A single real-time multiplex quantitative PCR (qPCR) assay for the simultaneous
      detection of Grapevine virus A, B and D (GVA, GVB and GVD) was developed, using
      three different fluorescently labeled minor groove binding probes. This multiplex
      RT-qPCR was compared to singleplex RT-qPCR designed specifically for each virus
      and a conventional multiplex RT-PCR. The capacity of the multiplex RT-qPCR assay
      in detecting the three vitiviruses in mixed infections from a range of virus
      concentrations in the host was assessed. A series of cDNA derived from 48
      different grapevine cultivars obtained from diverse geographical regions infected
      with various isolates and strains of GVA, GVB and GVD were subjected to
      singleplex, multiplex RT-qPCR, and conventional multiplex RT-PCR testing. The
      results showed that the developed multiplex RT-qPCR assay was a cost-effective
      diagnostic tool that could streamline the testing of grapevine vitiviruses, and
      replace the singleplex RT-qPCR assays, thus reducing time and labor while
      retaining the same sensitivity and specificity. In particular, no significant
      differences in detection limits were found between singleplex and multiplex RT
      qPCR and specificity was not affected by the inclusion of the three primer/probe
      combinations within a multiplex RT-qPCR. Comparing the viral load for each virus
      using singleplex and multiplex RT-qPCR assays revealed no significant differences
      between the two assays in detecting GVB and GVD. However, while in detecting GVA
      using singleplex RT-qPCR assay, viral load was higher. Finally, the multiplex RT
      qPCR assay was also more sensitive and time efficient than the conventional
      multiplex RT-PCR that was designed using degenerate primers to detect GVA, GVB
      and GVD. This multiplex RT-qPCR method could detect viruses in 95.83% of mixed
      infected samples as compared to 77.08% for multiplex RT-PCR. 

PMID- 23973786
TI  - Neuroprotective effects of Polygonum multiflorum extract against glutamate
      induced oxidative toxicity in HT22 hippocampal cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dried roots of Polygonum multiflorum have
      traditionally been used in the retarding of aging process in East Asian countries
      and its extracts exhibit anti-oxidative activities. MATERIALS AND METHODS:
      Neuroprotective effects of ethyl acetate extract from Polygonum multiflorum
      (EEPM) were investigated against glutamate-induced oxidative cell death in HT22
      hippocampal cells. Cell viability, cytotoxicity, morphological, flow cytometry,
      and Western blot assays were performed in order to observe alterations of
      neuronal cell survival or death related pathways. RESULTS: Pretreatment with EEPM
      resulted in significantly decreased glutamate-induced neurotoxicity and also
      resulted in drastically inhibited glutamate-induced apoptotic and necrotic
      neuronal death. To elucidate possible pathways of neuroprotection by EEPM, we
      explored the activation of mitogen activated protein kinases (MAPKs),
      phosphatidylinositol-3-kinase, and cAMP responsive element binding protein
      (CREB). Treatment with glutamate alone led to activation of extracellular
      regulated kinase (ERK), Jun N-terminal kinase, and p38 during the late phase
      after glutamate exposure, but pretreatment with EEPM resulted in significantly
      attenuated activation of these proteins. Pretreatment with EEPM resulted in
      increased activation of CREB. The specific inhibitors of ERK and p38, PD98059 and
      SB203580, abrogated the neuroprotective effects of EEPM. When we evaluated
      calpain I and striatal-enriched protein tyrosine phosphatase (STEP), active form
      of calpain I was significantly increased after glutamate exposure, and, along
      with this, active form of STEP showed a decrease. Pretreatment with EEPM resulted
      in significant recovery of pro-calpain I and active form of STEP caused by
      glutamate. Co-treatment with calpain inhibitor ALLN and EEPM had a synergistic
      effect on neuronal death and contributed to blockade of activation of both ERK
      and p38 with increased activation of CREB. CONCLUSIONS: These results suggest
      that Polygonum multiflorum extract may have neuroprotective effects through both
      alleviation of ERK and p38 activation with increased activation of CREB under
      oxidative stress and has potential as a therapeutic intervention for treatment of
      oxidative neuronal death.

PMID- 23973787
TI  - Paeoniflorin, the main active constituent of Paeonia lactiflora roots, attenuates
      bleomycin-induced pulmonary fibrosis in mice by suppressing the synthesis of type
      I collagen.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In the theory of traditional Chinese medicine,
      pulmonary fibrosis (PF) belongs to pulmonary arthralgia, which means blood stasis
      in lung tissue. The roots of Paeonia lactiflora Pall are usually used to relieve
      the symptoms of this disease by promoting blood circulation and removing blood
      stasis. Paeoniflorin, the main active ingredient of P. lactiflora, may have anti
      PF potential. AIM OF STUDY: This study aimed to investigate the effects and
      underlying mechanisms of paeoniflorin on bleomycin (BLM)-induced PF in mice.
      MATERIALS AND METHODS: The PF model was established in mice by an intratracheal
      instillation of BLM. Paeoniflorin (25, 50, 100mg/kg) and prednisone (6mg/kg), as
      a positive control, were orally administered for consecutive 21 days.
      Histopathological changes were evaluated by hematoxylin and eosin stain and
      Masson's trichrome stain. The content of hydroxyproline was detected by using
      kits. The contents of type I collagen, TGF-beta1 and IFN-gamma were detected by
      ELISA. The levels of alpha-SMA, Smad4, Smad7 and the phosphorylations of Smad2/3
      were detected by western blot. The mRNA expressions of MMP-1 and TIMP-1 were
      detected by RT-PCR. RESULTS: In mice treated with BLM, paeoniflorin (50mg/kg)
      significantly prolonged the survival periods, attenuated infiltration of
      inflammatory cells, interstitial fibrosis, and deposition of extracellular matrix
      in lung tissues. It also decreased the contents of hydroxyproline (a marker of
      collagens), type I collagen and alpha-SMA (an indicator of myofibroblasts) in
      lung tissues of mice. Paeoniflorin down-regulated the expressions of TGF-beta1,
      Smad4 and the phosphorylations of Smad2/3, while up-regulated the expression of
      Smad7 in lung tissues. Moreover, paeoniflorin increased the content of IFN-gamma.
      But, it only slightly affected mRNA expressions of MMP-1 and TIMP-1 in lung
      tissues of mice. CONCLUSIONS: Paeoniflorin attenuates PF by suppressing type I
      collagen synthesis via inhibiting the activation of TGF-beta/Smad pathway and
      increasing the expression of IFN-gamma.

PMID- 23973788
TI  - Baicalin can scavenge peroxynitrite and ameliorate endogenous peroxynitrite
      mediated neurotoxicity in cerebral ischemia-reperfusion injury.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Baicalin is one of the principal flavonoids
      isolated from the dried root of Scutellaria baicalensis Georgi that has long been
      used to treat ischemic stroke. However, its neuroprotective mechanisms against
      cerebral ischemia injury are poorly understood. AIM OF THE STUDY: To explore the
      neuroprotective mechanisms of baicalin against cerebral ischemia reperfusion
      injury. MATERIAL AND METHODS: In chemical systems, we conducted electron
      paramagnetic resonance (EPR) spin trapping experiments to evaluate the scavenging
      effects of baicalin on superoxide and nitric oxide, and mass spectrometry (MS)
      studies on the reaction of baicalin and peroxynitrite. In cellular experiments,
      we investigated the effects of baicalin against extraneous and endogenous
      peroxynitrite mediated neurotoxicity in SH-SY5Y cells treated with peroxynitrite
      donor, synthesized peroxynitrite and exposed to oxygen glucose deprivation and
      reoxygenation (OGD/RO) in vitro. Moreover, we studied the neuroprotective effects
      of baicalin by using a rat model of middle cerebral artery occlusion in vivo.
      FeTMPyP, a peroxynitrite decomposition catalyst, was used as positive control.
      Cell viability and apoptotic cell death was accessed by MTT assay and TUNEL assay
      respectively; 3-nitrotyrosine formation and infarction volume were detected by
      immunostaining experiments and TTC staining respectively. RESULTS: Baicalin
      revealed strong antioxidant ability by directly scavenging superoxide and
      reacting with peroxynitrite. Baicalin protected the neuronal cells from
      extraneous and endogenous peroxynitrite-induced neurotoxicity. In ischemia
      reperfused brains, baicalin inhibited the formation of 3-nitrotyrosine, reduced
      infarct size and attenuated apoptotic cell death, whose effects were similar to
      FeTMPyP. CONCLUSIONS: Baicalin can directly scavenge peroxynitrite and the
      peroxynitrite-scavenging ability contributes to its neuroprotective mechanisms
      against cerebral ischemia reperfusion injury.

PMID- 23973790
TI  - Structural elucidation studies of 15-membered azalide macrocycles using H/D
      exchange and ESI-MS(n.).
AB  - A comprehensive study of fragmentation pathways of 15-membered azalide
      macrocycles using electrospray ionisation with multistage mass spectrometry (ESI
      MS(n)) is presented in this work. Hydrogen/deuterium (H/D) exchange experiments
      and high-resolution mass spectrometry were used to investigate the proposed
      fragmentation pathways. In addition, the fragmentation patterns of sodium adduct
      ions [M+Na](+) of the macrocycles were also investigated as the presence of an
      alkali metal interacting with the aglycone ring influences the product-ion
      spectra. 

PMID- 23973789
TI  - Dematin, a human erythrocyte cytoskeletal protein, is a substrate for a
      recombinant FIKK kinase from Plasmodium falciparum.
AB  - P. falciparum causes the most deadly form of malaria, resulting from the
      adherence of infected red blood cells to blood vessels. During the blood stage of
      infection, the parasite secretes a large number of proteins into the host
      erythrocyte. The secretion of a 20-member family of protein kinases known as FIKK
      kinases, after a conserved Phe-Ile-Lys-Lys sequence motif, is unique to P.
      falciparum. Identification of physiological substrates of these kinases may
      provide perspective on the importance of FIKK kinase activity to P. falciparum
      virulence. We demonstrate, for the first time, the heterologous expression and
      purification of a FIKK kinase (PfFk4.1, PFD1165w). The recombinant kinase is
      active against general substrates and phosphorylates itself. Having demonstrated
      kinase activity, we incubated recombinant Fk4.1 with parasite and human
      erythrocyte lysates. No parasite-derived substrates were identified. However,
      treatment of erythrocyte ghosts shows that the FIKK kinase Fk4.1 phosphorylates
      dematin, a cytoskeletal protein found at the red blood cell spectrin-actin
      junction. 

PMID- 23973791
TI  - Development and validation of a sensitive LC-MS/MS assay for the simultaneous
      quantification of allitinib and its two metabolites in human plasma.
AB  - Allitinib, also known as AST1306, is a novel irreversible inhibitor of the
      epidermal growth factor receptors 1 and 2. Allitinib is currently used in
      clinical trial to treat solid tumors. A previous study showed that allitinib is
      extensively metabolized in humans. Amide hydrolysis metabolite (M6) and 29,30
      dihydrodiol allitinib (M10) are the major metabolites in circulation. To study
      the pharmacokinetics of allitinib and its two major metabolites in cancer
      patients, a rapid, sensitive and reliable LC-MS/MS method was developed and
      validated for the simultaneous determination of allitinib, M6 and M10 in human
      plasma. After simple protein precipitation, the analytes and the combined
      internal standards (lapatinib and NB-2, an analog of allitinib) were separated on
      a Zorbax Eclipase XDB C18 column (50 mm * 4.6 mm, 1.8 MUm, Agilent) using a
      mobile phase of 5 mM ammonium acetate with 0.1% formic acid (phase A) and 50%
      (v/v) methanol in acetonitrile (phase B) with gradient elution. Mass
      spectrometric detection was conducted by atmospheric-pressure chemical ionization
      in positive ion multiple reaction monitoring modes using AB Sciex Triple Quad
      6500 system. Linear calibration curves were obtained for the following
      concentration range: 0.300-200 ng/ml for allitinib; 0.030-20.0 ng/ml for M6; and
      0.075-50.0 ng/ml for M10. Intra-day and inter-day accuracy and precision were
      within the acceptable limits of +/-15% at all of the concentrations. The method
      was successfully applied to a preliminary clinical pharmacokinetic study
      following oral administration of allitinib tosylate tablets in cancer patients. 

PMID- 23973792
TI  - The role of working memory in achievement goal pursuit.
AB  - The present research examined the role of working memory in the pursuit of
      qualitatively different achievement goals. Pursuit of a mastery-approach goal
      entails a focus on developing self-referential competence while a performance
      approach goal entails a focus on demonstrating normative competence. Across two
      experiments it was found that, when working memory is loaded, individuals
      pursuing a mastery-approach goal experienced larger performance decrements than
      individuals pursuing a performance-approach goal or those in a no-goal control.
      It was also found that reliance upon working memory intensive strategies
      (explicit strategies) was more evident for those in a mastery-approach condition,
      whereas reliance upon less working memory intensive strategies (implicit
      strategies) was more evident for those in the performance-approach condition.
      Results suggest that a motivated focus on developing self-referential skill
      relies heavily on working memory, facilitated by the use of deliberative, 'step
      by-step' strategies during goal pursuit. Conversely, a focus on demonstrating
      normative skill depends less on working memory, facilitated by the use of more
      heuristic 'short-cut' strategies during goal pursuit. These findings show, for
      the first time, that working memory plays an important, but selective, role in
      achievement goal pursuit. 

PMID- 23973793
TI  - Avoiding the problem state bottleneck by strategic use of the environment.
AB  - We investigated whether environmental support can be used to circumvent the
      problem state bottleneck in human multitasking. Previously, it was shown that
      people can only maintain a single chunk of information in their problem state
      resource, the central part of working memory. Consequently, when the problem
      state resource was required by multiple tasks concurrently, performance
      decreased. This phenomenon was termed the problem state bottleneck. To
      investigate whether the environment can be used to circumvent this bottleneck, we
      conducted an experiment with two main conditions. In the No-Support condition we
      replicated an earlier experiment that indicated the existence of the problem
      state bottleneck. In the Support condition we presented external cues, reducing
      the load on the problem state resource. To support the results of the experiment
      we present a computational cognitive model. The experiment and model indicated
      that the problem state bottleneck can be avoided by using external cues. However,
      subjects only used external cues when this led to faster behavior. These results
      were interpreted in the light of the Soft Constraints Hypothesis, which states
      that humans always follow the fastest strategy possible, as opposed to the most
      accurate strategy. 

PMID- 23973794
TI  - Monitoring and meta-metacognition in the own-race bias.
AB  - Although there is a great deal of research focused on identification issues
      related to own-versus other-race faces very few experiments have explored whether
      metacognitive monitoring contributes to the own-race bias. In the current
      experiment the typical own-race bias paradigm was modified so that type-2 signal
      detection measures (e.g. Higham & Arnold, 2007a,b) could be used to directly
      measure metacognitive monitoring at retrieval. A second goal of the experiment
      was to explore whether self-reported confidence ratings differed depending on
      whether they were directed at answer accuracy (e.g., judging a face as "studied")
      versus at decisions about that answer (e.g., volunteering vs. withholding that
      answer). Overall the results demonstrated that monitoring does contribute to the
      own-race bias, in that participants were better at monitoring their memory for
      own-race faces. Further, there was a significant difference between the two
      confidence measures, and the pattern of this difference depended on whether
      responses had been volunteered or withheld. 

PMID- 23973795
TI  - Feeding infants below 29 weeks' gestation with abnormal antenatal Doppler:
      analysis from a randomised trial.
AB  - OBJECTIVE: To describe feeding and gastrointestinal outcomes in growth-restricted
      infants <29 weeks' gestation and to determine the rate of feed advancement which
      they tolerate. DESIGN: Analysis of prospectively collected data from a randomised
      feeding trial, the Abnormal Doppler Enteral Prescription Trial (ADEPT). SETTING:
      54 neonatal units in the UK and Ireland. PARTICIPANTS: 404 preterm, growth
      restricted infants with abnormal antenatal Doppler studies from ADEPT. 83 infants
      <29 weeks and 312 infants >= 29 weeks' gestation were included in this analysis.
      INTERVENTIONS: In ADEPT, infants were randomised to start milk 'early' on day 2
      after birth, or 'late' on day 6. Subsequent feed advancement followed a regimen,
      which should have achieved full feeds by day 16 in the early and day 20 in the
      late group. MAIN OUTCOME MEASURES: Full feeds were achieved later in infants <29
      weeks; median age 28 days {IQR 22-40} compared with 19 days {IQR 17-23} in
      infants >= 29 weeks (HR 0.35, 95% CI 0.3 to 0.5). The incidence of necrotising
      enterocolitis was also higher in this group; 32/83 (39%) compared to 32/312 (10%)
      in those >= 29 weeks (RR 3.7, 95% CI 2.4 to 5.7). Infants <29 weeks tolerated
      very little milk for the first 10 days of life and reached full feeds 9 days
      later than predicted from the trial regimen. CONCLUSIONS: Growth-restricted
      infants born <29 weeks' gestation with abnormal antenatal Doppler failed to
      tolerate even the careful feeding regimen of ADEPT. A slower advancement of feeds
      may be required for these infants. TRIAL REGISTRATION NUMBER: ISRCTN87351483.

PMID- 23973796
TI  - DNA methylation analysis of BDNF gene promoters in peripheral blood cells of
      schizophrenia patients.
AB  - Accumulating evidence suggests that epigenetic alterations in brain-derived
      neurotrophic factor (BDNF) promoters are associated with the pathophysiology of
      psychiatric disorders. Epigenetic changes in BDNF were reported not only in brain
      tissues but also in other tissues, including peripheral blood cells (PBC) and
      saliva. We examined DNA methylation levels of BDNF promoters I and IV using
      genomic DNA derived from PBC of healthy controls (n=100), and patients with
      schizophrenia (n=100), all from the Japanese population, by pyrosequencing. The
      examined CpG sites were chosen based on previous epigenetic studies that reported
      altered DNA methylation. We found a significantly higher level of methylation at
      BDNF promoter I in patients with schizophrenia compared to controls, although the
      difference was small. Subsequent analysis revealed that in controls, the
      methylation level of BDNF promoters was associated with sex, and the methylation
      difference observed in promoter I was more prominent in male patients with
      schizophrenia. Epigenetic alteration of BDNF in the PBC might reflect the
      pathophysiology of schizophrenia, and could be a potential biomarker. 

PMID- 23973797
TI  - AVT is involved in the regulation of ion transport in the intestine of the sea
      bream (Sparus aurata).
AB  - The intestine of marine fish plays a crucial role in ion homeostasis by selective
      processing of ingested fluid. Although arginine vasotocin (AVT) is suggested to
      play a role in ion regulation in fish, its action in the intestine has not been
      demonstrated. Thus, the present study investigated in vitro the putative role of
      AVT in intestinal ion transport in the sea bream (Sparus aurata). A cDNA encoding
      part of an AVT receptor was isolated and phylogenetic analysis revealed it
      clustered with the V1a2-type receptor clade. V1a2 transcripts were expressed
      throughout the gastrointestinal tract, from esophagus to rectum, and were most
      abundant in the rectum regardless of long-term exposure to external salinities of
      12, 35 or 55p.p.t. Basolateral addition of AVT (10(-6)M) to the anterior
      intestine and rectum of sea bream adapted to 12, 35 or 55p.p.t. mounted in Ussing
      chambers produced rapid salinity and region dependent responses in short circuit
      current (Isc), always in the absorptive direction. In addition, AVT stimulation
      of absorptive Isc conformed to a dose-response curve, with significant effects
      achieved at 10(-8)M, which corresponds to physiological values of plasma AVT for
      this species. The effect of AVT on intestinal Isc was insensitive to the CFTR
      selective inhibitor NPPB (200MUM) applied apically, but was completely abolished
      in the presence of apical bumetanide (200MUM). We propose a role for AVT in the
      regulation of ion absorption in the intestine of the sea bream mediated by an
      absorptive bumetanide-sensitive mechanism, likely NKCC2. 

PMID- 23973798
TI  - Oxidized-phospholipids in reconstituted high density lipoprotein particles affect
      structure and function of recombinant paraoxonase 1.
AB  - Paraoxonase 1 (PON1) is an HDL-associated enzyme and exhibits anti-inflammatory,
      anti-diabetic, and anti-atherogenic properties. Association of PON1 to HDL
      particles increases the stability and activity of PON1 and is important for the
      normal functioning of the enzyme. HDL particles are made up of lipid and protein
      constituents and apolipoprotein A-I (apoA-I) is a principal protein constituent
      of HDL that facilitates various biological activities of HDL. In many disease
      conditions the oxidized phospholipid (Ox-PL) content of HDL is found to be
      increased and an inverse correlation between the activity of PON1 and oxidation
      of the HDL is observed. However, the molecular details of the inhibitory action
      of the Ox-PL-containing HDL on the function of PON1 are not clear yet. In this
      study we have assembled reconstituted HDL (rHDL) particles with and without Ox-PL
      and compared their effect on the structure and function of (13)C-labeled
      recombinant PON1 ((13)C-rPON1) by employing attenuated total reflectance Fourier
      transformed infrared (ATR-FTIR) spectroscopy and enzymatic assay. Our results
      show that the presence of the Ox-PL in the rHDL particles alters the structure of
      rPON1 and decreases its lactonase activity. 

PMID- 23973799
TI  - LIF-dependent primitive neural stem cells derived from mouse ES cells represent a
      reversible stage of neural commitment.
AB  - Primitive neural stem cells (NSCs) define an early stage of neural induction,
      thus provide a model to understand the mechanism that controls initial neural
      commitment. In this study, we investigated primitive NSCs derived from mouse
      embryonic stem cells (ESCs). By genome-wide transcriptional profiling, we
      revealed their unique signature and depicted the molecular changes underlying
      critical cell fate transitions during early neural induction at a global level.
      Together with qRT-PCR analysis, our data illustrated that primitive NSCs retained
      expression of key pluripotency genes Oct4 and Nanog, while exhibiting repression
      of other pluripotency-related genes Zscan4, Foxp1 and Dusp9 and up-regulation of
      neural markers Sox1 and Hes1. The early differentiation feature in primitive NSCs
      was also supported by their intermediate characters on cell cycle profiles.
      Moreover, re-plating primitive NSCs back to ESC culture condition could reverse
      them back to ESC stage, as shown by reversible regulation of marker genes, cell
      cycle profile changes and enhanced embryoid body formation. In addition, our
      microarray analysis also identified genes differentially expressed in primitive
      NSCs, and loss-of-function analysis demonstrated that Hes1 and Ccdc141 play
      important function at this stage, opening up an opportunity to further understand
      the regulation of early neural commitment. 

PMID- 23973801
TI  - Impact of ADHD symptoms on autism spectrum disorder symptom severity.
AB  - Despite the official exclusion criteria for autism spectrum disorder (ASD) and
      attention deficit/hyperactivity disorder (ADHD) in the DSM-IV and ICD-10,
      patients with ASD often show ADHD symptoms. We aimed to examine the potential
      influence of ADHD symptoms on autistic psychopathology in a large sample of
      patients with ASD. We tested the hypothesis that patients with ASD and an
      additional ADHD (ASD+) would show a higher severity of autistic symptoms than
      those with ASD only (ASD-). We measured autistic symptoms using the autism
      diagnostic observation schedule (ADOS-G), the autism diagnostic interview (ADI
      R), and the social responsiveness scale (SRS). To measure overall psychopathology
      and ADHD symptoms, we used the child behavior checklist (CBCL) and the ADHD
      rating scale (FBB-ADHS), respectively. Group differences between the ASD+ and the
      ASD- group (group division was conducted according to the results of the FBB
      ADHS) were calculated using a univariate analysis of variance (ANOVA). The ASD+
      group showed a greater severity of autistic symptoms than the ASD- group,
      measured by the SRS and the ADI-R. Especially in the social interaction subscale
      (ADI-R), a significantly higher symptom severity was found in the ASD+ group. No
      significant group differences were found regarding autistic symptoms measured by
      the ADOS-G. Patients with ASD and an additional ADHD expressed a stronger
      severity of autistic symptoms than patients with ASD only. According to our
      results, the possibility of a co-diagnosis of ADS and ADHD, as is being planned
      in the DSM-5, is in line with earlier studies, is highly reasonable, will
      simplify research, and have therapeutic implications. 

PMID- 23973800
TI  - Scalable expansion of human induced pluripotent stem cells in the defined xeno
      free E8 medium under adherent and suspension culture conditions.
AB  - Large-scale production of human induced pluripotent stem cells (hiPSCs) by robust
      and economic methods has been one of the major challenges for translational
      realization of hiPSC technology. Here we demonstrate a scalable culture system
      for hiPSC expansion using the E8 chemically defined and xeno-free medium under
      either adherent or suspension conditions. To optimize suspension conditions
      guided by a computational simulation, we developed a method to efficiently expand
      hiPSCs as undifferentiated aggregates in spinner flasks. Serial passaging of two
      different hiPSC lines in the spinner flasks using the E8 medium preserved their
      normal karyotype and expression of undifferentiated state markers of TRA-1-60,
      SSEA4, OCT4, and NANOG. The hiPSCs cultured in spinner flasks for more than 10
      passages not only could be remained pluripotent as indicated by in vitro and in
      vivo assays, but also could be efficiently induced toward mesodermal and
      hematopoietic differentiation. Furthermore, we established a xeno-free protocol
      of single-cell cryopreservation and recovery for the scalable production of
      hiPSCs in spinner flasks. This system is the first to enable an efficient scale
      up bioprocess in completely xeno-free condition for the expansion and
      cryopreservation of hiPSCs with the quantity and quality compliant for clinical
      applications. 

PMID- 23973802
TI  - Optimizations to achieve high-level expression of cytochrome P450 proteins using
      Escherichia coli expression systems.
AB  - Recombinant expression of membrane-bound cytochrome P450s in bacterial expression
      systems provide a well-established system capable of producing large yields of
      catalytically active protein. As the biochemical knowledge regarding cytochrome
      P450s increases, so does the efficiency of protein expression through various
      modifications that do not disrupt the functional properties of the protein of
      interest. Changes such as N-terminal modifications, reduction of secondary mRNA
      structure, bacterial codon usage, selection of vector and host strain, as well as
      varying external growth conditions all appear to influence protein expression.
      Several optimizations are often required for sufficient expression of cytochrome
      P450s at the desired cellular localization. This review aims to comprehensively
      summarize and update the significant advances made in membrane protein P450
      expression in bacterial expression systems. 

PMID- 23973803
TI  - Efficient production of anti-fluorescein and anti-lysozyme as single-chain anti
      body fragments (scFv) by Brevibacillus expression system.
AB  - Expression of scFv in Brevibacillus choshinensis was tested using combinations of
      three different promoters and four different secretion signals. Two model scFv
      constructs, i.e., His-scFvFLU and His-scFvHEL, were successfully expressed with
      some of the combinations. Ni Sepharose column and size exclusion chromatography
      resulted in fairly pure preparations of these two proteins. The purified His
      scFvFLU inhibited fluorescence from fluorescein, while the purified His-scFvHEL
      inhibited lysozyme activity. Relatively high yield of His-scFvFLU (~40%) and His
      scFvHEL (~30%) was achieved with the expression and purification system described
      here. 

PMID- 23973805
TI  - Expression profile of a clonal insulin-expressing epithelial cell in the thymus.
AB  - BACKGROUND: Type 1 diabetes is an autoimmune disease resulting from the
      destruction of pancreatic beta-cells. One of the main antigens targeted in this
      auto reactive response is insulin. It has been shown that insulin is expressed in
      small amounts in the thymus, and more specifically in the medullary thymic
      epithelial cells (mTECs), which also express a variety of other tissue-specific
      antigens. This thymic expression enables the maintenance of self-tolerance, and
      is essential in preventing auto-immune disease. Our laboratory has created a
      mouse mTEC clonal cell line specifically expressing insulin in order to better
      understand the regulatory mechanisms of this ectopic expression of insulin. In
      this study, we compared the insulin expressing cell line to an insulin non
      expressing mTEC line by genome-wide expression profiling. RESULTS: The most
      important difference was overexpression of CD34 in the insulin expressing clone,
      confirmed by Real-time Rt-PCR and flow cytometry. Cells in the thymus expressing
      higher levels of CD34 were found to contain higher levels of insulin and, to a
      lesser extent, Aire, a master regulator of self-antigen expression in the thymus.
      The cells expressing CD34 were not enriched in CD80, a known mTEC maturity
      marker. CONCLUSION: CD34 may be a specific marker for functionality, with some
      specificity for insulin.

PMID- 23973804
TI  - TORC2 signaling antagonizes SKN-1 to induce C. elegans mesendodermal embryonic
      development.
AB  - The evolutionarily conserved target of rapamycin (TOR) kinase controls
      fundamental metabolic processes to support cell and tissue growth. TOR functions
      within the context of two distinct complexes, TORC1 and TORC2. TORC2, with its
      specific component Rictor, has been recently implicated in aging and regulation
      of growth and metabolism. Here, we identify rict-1/Rictor as a regulator of
      embryonic development in C. elegans. The transcription factor skn-1 establishes
      development of the mesendoderm in embryos, and is required for cellular
      homeostasis and longevity in adults. Loss of maternal skn-1 function leads to mis
      specification of the mesendodermal precursor and failure to form intestine and
      pharynx. We found that genetic inactivation of rict-1 suppressed skn-1-associated
      lethality by restoring mesendodermal specification in skn-1 deficient embryos.
      Inactivation of other TORC2 but not TORC1 components also partially rescued skn-1
      embryonic lethality. The SGK-1 kinase mediated these functions downstream of rict
      1/TORC2, as a sgk-1 gain-of-function mutant suppressed the rict-1 mutant
      phenotype. These data indicate that TORC2 and SGK-1 antagonize SKN-1 during
      embryonic development. 

PMID- 23973806
TI  - Exploiting new tools for iron bio-fortification of rice.
AB  - Rice is one of the most important staple crops and efficient iron (Fe) adsorption
      during growth not only improves rice yield, but also enriches this essential
      micronutrient in rice grains to address Fe deficiency in humans. In this article,
      we review updates on research into the molecular mechanisms regulating Fe uptake
      from soil and its transport from roots to shoots to seeds in rice plants.
      Understanding the regulation and expression of genes involved in Fe homeostasis
      will benefit the development of variants with enhanced Fe utilization to improve
      rice output and quality. 

PMID- 23973807
TI  - Anticancer bioactivity of compounds from medicinal plants used in European
      medieval traditions.
AB  - Since centuries, natural compounds from plants, animals and microorganisms were
      used in medicinal traditions to treat various diseases without a solid scientific
      basis. Recent studies have shown that plants that were used or are still used in
      the medieval European medicine are able to provide relieve for many diseases
      including cancer. Here we summarize impact and effect of selected purified active
      natural compounds from plants used in European medieval medicinal traditions on
      cancer hallmarks and enabling characteristics identified by Hanahan and Weinberg.
      The aim of this commentary is to discuss the pharmacological effect of pure
      compounds originally discovered in plants with therapeutic medieval use. Whereas
      many reviews deal with Ayurvedic traditions and traditional Chinese medicine, to
      our knowledge, the molecular basis of European medieval medicinal approaches are
      much less documented. 

PMID- 23973808
TI  - Tuning cell cycle of insect cells for enhanced protein production.
AB  - The eukaryotic cell cycle consists of many checkpoints during which certain
      conditions must be met before passing to subsequent stages. These safeguards
      ensure cells' integrity and survival, but may also limit growth and protein
      synthesis in protein production processes. In this work, we employ metabolic
      engineering principles to "tune" the cell cycle to overcome checkpoint processes
      in order to facilitate faster cell growth, and independently, arrest the cell
      cycle in gap1 (G1) phase for greater protein productivity. Specifically, we
      identified the complete cyclin E (cycE) cDNA sequence from industrially relevant,
      Trichoplusia ni (T. ni) derived High FiveTM genomes. We then both knocked down
      (through RNA interference; RNAi) and overexpressed (on an expression plasmid)
      cycE gene expression to tune the cell phenotype. We successfully up- and down
      regulated cycE transcription, enhancing and hindering cell growth, respectively.
      We also measured the effects of titrated cycE expression on the cell cycle phase
      distribution. Finally, we investigated the dose-dependent effects of dsCycE on
      recombinant protein production using the baculovirus expression system and
      demonstrated a nearly 2-fold increase in expression of model protein (GFPuv). 

PMID- 23973809
TI  - Real-time luminescence imaging of cellular ATP release.
AB  - Extracellular ATP and other purines are ubiquitous mediators of local
      intercellular signaling within the body. While the last two decades have
      witnessed enormous progress in uncovering and characterizing purinergic receptors
      and extracellular enzymes controlling purinergic signals, our understanding of
      the initiating step in this cascade, i.e., ATP release, is still obscure. Imaging
      of extracellular ATP by luciferin-luciferase bioluminescence offers the advantage
      of studying ATP release and distribution dynamics in real time. However, low
      light signal generated by bioluminescence reactions remains the major obstacle to
      imaging such rapid processes, imposing substantial constraints on its spatial and
      temporal resolution. We have developed an improved microscopy system for real
      time ATP imaging, which detects ATP-dependent luciferin-luciferase luminescence
      at ~10 frames/s, sufficient to follow rapid ATP release with sensitivity of ~10
      nM and dynamic range up to 100 MUM. In addition, simultaneous differential
      interference contrast cell images are acquired with infra-red optics. Our imaging
      method: (1) identifies ATP-releasing cells or sites, (2) determines absolute ATP
      concentration and its spreading manner at release sites, and (3) permits analysis
      of ATP release kinetics from single cells. We provide instrumental details of our
      approach and give several examples of ATP-release imaging at cellular and tissue
      levels, to illustrate its potential utility.

PMID- 23973810
TI  - Detection of 3'->5' exonuclease activity using a metal-based luminescent switch
      on probe.
AB  - A luminescent iridium(III) complex has been discovered to be selective for G
      quadruplex DNA, and was employed in a label-free G-quadruplex-based detection
      assay for 3'->5' exonuclease activity in aqueous solution. A proof-of-concept of
      this assay has been demonstrated by using prokaryotic exonuclease III (ExoIII) as
      a model enzyme. In this assay, a G-quadruplex-forming hairpin oligonucleotide
      (hairpin-G4 DNA, 5'-GAG3TG4AG3TG4A2GCAGA2G2ATA2CT2C4AC3TC4AC3TC-3') initially
      exists in a duplex conformation, resulting in a low luminescence signal due to
      the weak interaction between the iridium(III) complex and duplex DNA. Upon
      digestion by ExoIII, the guanine-rich sequence is released and folds into a G
      quadruplex, which greatly enhances the luminescence emission of the iridium(III)
      probe. This method was highly sensitive for 3'->5' exonuclease over other DNA
      modifying enzymes. 

PMID- 23973811
TI  - Use of Bru-Seq and BruChase-Seq for genome-wide assessment of the synthesis and
      stability of RNA.
AB  - Gene expression studies commonly examine total cellular RNA, which only provides
      information about its steady-state pool of RNA. It remains unclear whether
      differences in the steady-state reflects variable rates of transcription or RNA
      degradation. To specifically monitor RNA synthesis and degradation genome-wide,
      we developed Bru-Seq and BruChase-Seq. These assays are based on metabolic pulse
      chase labeling of RNA using bromouridine (Bru). In Bru-Seq, recently labeled RNAs
      are sequenced to reveal spans of nascent transcription in the genome. In BruChase
      Seq, cells are chased in uridine for different periods of time following Bru
      labeling, allowing for the isolation of RNA populations of specific ages. Here we
      describe these methodologies in detail and highlight their usefulness in
      assessing RNA synthesis and stability as well as splicing kinetics with examples
      of specific genes from different human cell lines. 

PMID- 23973812
TI  - Osmotic pump tablets for delivery of antiretrovirals to the vaginal mucosa.
AB  - Vaginal pre-exposure prophylaxis has focused heavily on gel formulations. Low
      adherence linked with frequent dosing and short therapeutic duration has emerged
      as the major reason for inconsistent efficacy outcomes with gels in clinical
      trials. Osmotic pumps can achieve versatile drug release profiles however, have
      not been explored for vaginal delivery. In this report, we describe an osmotic
      pump tablet (OPT) that can deliver antiretrovirals for several days. We also
      describe configuring the OPT for pH sensitive delivery where the drug delivery
      system consistently delivers an antiretroviral at vaginal pH and then gives a
      burst release triggered by a coitally associated pH increase. We have
      investigated the vaginal OPT for multiple day delivery of a potent
      antiretroviral, IQP-0528 in a sheep model. To effectively register spatial drug
      distribution we also engineered a tool to precisely collect multiple vaginal
      fluid samples. In a 10-day duration post single application, high micromolar
      mucosal levels were obtained with peak concentration more than 6 logs higher than
      the EC50 of IQP-0528. Overall, our results show successful implementation of the
      osmotic pump technology for vaginal antiretroviral delivery. 

PMID- 23973813
TI  - Chemically and biologically synthesized CPP-modified gelonin for enhanced anti
      tumor activity.
AB  - The ineffectiveness of small molecule drugs against cancer has generated
      significant interest in more potent macromolecular agents. Gelonin, a plant
      derived toxin that inhibits protein translation, has attracted much attention in
      this regard. Due to its inability to internalize into cells, however, gelonin
      exerts only limited tumoricidal effect. To overcome this cell membrane barrier,
      we modified gelonin, via both chemical conjugation and genetic recombination
      methods, with low molecular weight protamine (LMWP), a cell-penetrating peptide
      (CPP) which was shown to efficiently ferry various cargoes into cells. Results
      confirmed that gelonin-LMWP chemical conjugate (cG-L) and recombinant gelonin
      LMWP chimera (rG-L) possessed N-glycosidase activity equivalent to that of
      unmodified recombinant gelonin (rGel); however, unlike rGel, both gelonin-LMWPs
      were able to internalize into cells. Cytotoxicity studies further demonstrated
      that cG-L and rG-L exhibited significantly improved tumoricidal effects, with
      IC50 values being 120-fold lower than that of rGel. Moreover, when tested against
      a CT26 s.c. xenograft tumor mouse model, significant inhibition of tumor growth
      was observed with rG-L doses as low as 2 MUg/tumor, while no detectable
      therapeutic effects were seen with rGel at 10-fold higher doses. Overall, this
      study demonstrated the potential of utilizing CPP-modified gelonin as a highly
      potent anticancer drug to overcome limitations of current chemotherapeutic
      agents.

PMID- 23973815
TI  - Who's using treatment manuals? A national survey of practicing therapists.
AB  - Treatment manuals are currently the most common way treatments are disseminated
      to practicing clinicians, although little is known about the rates with which
      practicing therapists incorporate these manuals into their practice. In light of
      a widely acknowledged research-practice gap, understanding how often therapists
      are using manuals is important for shaping future dissemination efforts. This
      study collected data on rates of manual use among a national sample of mental
      health clinicians representative of those likely to be targeted in dissemination
      efforts (N = 756), as well as predictors of use. Results indicated that few
      clinicians (< 10%) routinely incorporated manuals into their practice, although
      most employed them to some degree. Predictors of manual use included greater
      openness to new treatments, younger age, and a cognitive-behavioral treatment
      orientation (ps < .05). Implications for future dissemination efforts are
      discussed.

PMID- 23973814
TI  - Multimodal delivery of irinotecan from microparticles with two distinct
      compartments.
AB  - In the last several decades, research in the field of drug delivery has been
      challenged with the fabrication of carrier systems engineered to deliver
      therapeutics to the target site with sustained and controlled release kinetics.
      Herein, we report the fabrication of microparticles composed of two distinct
      compartments: i) one compartment containing a pH responsive polymer, acetal
      modified dextran, and PLGA (polylactide-co-glycolide), and ii) one compartment
      composed entirely of PLGA. We demonstrate the complete release of dextran from
      the microparticles during a 10-hour period in an acidic pH environment and the
      complete degradation of one compartment in less than 24h. This is in congruence
      with the stability of the same microparticles in neutral pH over the 24-hour
      period. Such microparticles can be used as pH responsive carrier systems for drug
      delivery applications where their cargo will only be released when the optimum pH
      window is reached. The feasibility of the microparticle system for such an
      application was confirmed by encapsulating a cancer therapeutic, irinotecan, in
      the compartment containing the acetal-modified dextran polymer and the pH
      dependent release over a 5-day period was studied. It was found that upon pH
      change to an acidic environment, over 50% of the drug was first released at a
      rapid rate for 10h, similar to that observed for the dextran release, before
      continuing at a more controlled rate for 4 days. As such, these microparticles
      can play an important role in the fabrication of novel drug delivery systems due
      to the selective, controlled, and pH responsive release of their encapsulated
      therapeutics.

PMID- 23973816
TI  - Water beetle tolerance to salinity and anionic composition and its relationship
      to habitat occupancy.
AB  - Water salinity and ionic composition are among the main environmental variables
      that constrain the fundamental niches of aquatic species, and accordingly,
      physiological tolerance to these factors constitutes a crucial part of the
      evolution, ecology, and biogeography of these organisms. The present study
      experimentally estimated the fundamental saline and anionic niches of adults of
      two pairs of congeneric saline beetle species that differ in habitat preference
      (lotic and lentic) in order to test the habitat constraint hypothesis. Osmotic
      and anionic realised niches were also estimated based on the field occurrences of
      adult beetle species using Outlying Mean Index analysis and their relationship
      with experimental tolerances. In the laboratory, all of the studied species
      showed a threshold response to increased salinity, displaying high survival times
      when exposed to low and intermediate conductivity levels. These results suggest
      that these species are not strictly halophilic, but that they are able to
      regulate both hyperosmotically and hypoosmotically. Anionic water composition had
      a significant effect on salinity tolerance at conductivity levels near their
      upper tolerance limits, with decreased species survival at elevated sulphate
      concentrations. Species occupying lentic habitats demonstrated higher salinity
      tolerance than their lotic congeners in agreement with the habitat constraint
      hypothesis. As expected, realised salinity niches were narrower than fundamental
      niches and corresponded to conditions near the upper tolerance limits of the
      species. These species are uncommon on freshwater-low conductivity habitats
      despite the fact that these conditions might be physiologically suitable for the
      adult life stage. Other factors, such as biotic interactions, could prevent their
      establishment at low salinities. Differences in the realised anionic niches of
      congeneric species could be partially explained by the varying habitat
      availability in the study area. Combining the experimental estimation of
      fundamental niches with realised field data niche estimates is a powerful method
      for understanding the main factors constraining species' distribution at multiple
      scales, which is a key issue when predicting species' ability to cope with global
      change. 

PMID- 23973817
TI  - Utilisation of chemical signals by inquiline wasps in entering their host figs.
AB  - The fig tree, Ficus curtipes, hosts an obligate pollinating wasp, an undescribed
      Eupristina sp., but can also be pollinated by two inquiline (living in the
      burrow, nest, gall, or other habitation of another animal) wasps, Diaziella yangi
      and an undescribed Lipothymus sp. The two inquilines are unable to independently
      induce galls and depend on the galls induced by the obligate pollinator for
      reproduction and, therefore, normally enter receptive F. curtipes figs colonised
      by the obligate pollinators. However, sometimes the inquilines also enter figs
      that are not colonised by the pollinators, despite consequent reproductive
      failure. It is still unknown which signal(s) the inquilines use in entering the
      colonised and non-colonised figs. We conducted behavioural experiments to
      investigate several possible signals utilised by the inquilines in entering their
      host receptive figs. Our investigation showed that both inquiline species enter
      the receptive F. curtipes figs in response to the body odours of the obligate
      wasps and one of the main compounds emitted by the figs, 6-methyl-5-hepten-2-one.
      The compound was not found in the pollinator body odours, suggesting that the two
      inquiline wasps can utilise two signals to enter their host figs, which is
      significant for the evolution of the fig-fig wasp system. These inquilines could
      evolve to become mutualists of the figs if they evolve the ability to
      independently gall fig flowers; there is, however, another possibility that a
      monoecious Ficus species hosting such inquilines may evolve into a dioecious one
      if these inquilines cannot evolve the above-mentioned ability. Additionally, this
      finding provides evidence for the evolution of chemical communication between
      plants and insects. 

PMID- 23973818
TI  - Evidences for an ATP-sensitive potassium channel (KATP) in muscle and fat body
      mitochondria of insect.
AB  - In the present study, we describe the existence of mitochondrial ATP-dependent
      K(+) channel (mitoKATP) in two different insect tissues, fat body and muscle of
      cockroach Gromphadorhina coquereliana. We found that pharmacological substances
      known to modulate potassium channel activity influenced mitochondrial resting
      respiration. In isolated mitochondria oxygen consumption increased by about 13%
      in the presence of potassium channel openers (KCOs) such as diazoxide and
      pinacidil. The opening of mitoKATP was reversed by glibenclamide (potassium
      channel blocker) and 1 mM ATP. Immunological studies with antibodies raised
      against the Kir6.1 and SUR1 subunits of the mammalian ATP-sensitive potassium
      channel, indicated the existence of mitoKATP in insect mitochondria. MitoKATP
      activation by KCOs resulted in a decrease in superoxide anion production,
      suggesting that protection against mitochondrial oxidative stress may be a
      physiological role of mitochondrial ATP-sensitive potassium channel in insects. 

PMID- 23973819
TI  - Discovery of novel N-substituted carbazoles as neuroprotective agents with potent
      anti-oxidative activity.
AB  - Carbazole moiety is an important scaffold with a variety of biological
      applications, for example, anti-oxidative stress. Our previous synthesized
      carbazoles were screened for their neuroprotective properties against two
      individual oxidative stresses. Some of the new carbazole derivatives were
      observed with modest to good neuroprotective effects on neuronal cells HT22
      against cell injury induced by glutamate or homocysteic acid (HCA). Substituents
      introduced to the carbazole ring system play crucial roles in their biological
      activities. In particular, a bulky group favors the neuroprotective activity of
      the compounds. One of the new compounds, 6, showed the best neuroprotective
      effects, which might result from its anti-oxidative activity with a GSH
      independent mechanism. These findings might provide an alternative strategy for
      the development of novel carbazole derivatives for the treatment of CNS diseases
      such as Alzheimer's disease. 

PMID- 23973820
TI  - Novel cross-link breaker based on zwitterion structure: synthesis, structure and
      druggability studies.
AB  - It has been universally acknowledged that the increase in cardiac and vascular
      stiffness is due to the formation of advanced glycosylation end-products (AGEs).
      Research on the stable form of 3-(carboxymethyl)-4-methylthiazol bromide sodium
      salt (C6H7BrNNaO2S) showed that it had a notable effect on breaking the AGEs. Two
      compounds with novel structures, zwitterionic 3-(carboxymethyl)-4-methylthiazol
      (C6H7O2NS) and a dipolymer (C12H15O4N2S2Br) complex, were obtained. When compared
      with the forms of sodium salt and dipolymer, zwitterion had an obvious advantage
      in stability, solubility, synthesis and pH, which made the zwitterion a promising
      drug. The structure of sodium salt, dipolymer and zwitterion was comparatively
      analyzed by such methods as single crystal X-ray diffraction, ESI-MS, 1H NMR, FT
      IR and in situ IR.

PMID- 23973821
TI  - Synthesis and antimicrobial activity of novel 5-(1-adamantyl)-2-aminomethyl-4
      substituted-1,2,4-triazoline-3-thiones.
AB  - The reaction of 5-(1-adamantyl)-4-substituted-1,2,4-triazoline-3-thione 5a,b and
      10a,b with formaldehyde solution and various primary aromatic amines or 1
      substituted piperazines yielded the corresponding N-Mannich bases 6a-o, 7a-g and
      11a-i. The newly synthesized N-Mannich bases 6a-o, 7a-g and 11a-i were tested for
      in vitro inhibitory activities against a panel of Gram-positive and Gram-negative
      bacteria and the yeast-like pathogenic fungus Candida albicans. The compounds 6j,
      6l, 6m, 7a, 7b, 7c, 7d, 7f, 11a, 11b, 11c, 11d, 11e, 11f, 11h and 11i displayed
      moderate to good activity against the tested Gram-positive bacteria, while
      compounds 7c, 11c, 11d, 11f and 11h showed potent broad spectrum antibacterial
      activity. None of the newly synthesized compounds were proved to possess marked
      activity against C. albicans. 

PMID- 23973822
TI  - Polyoxygenated cinnamoylcoumarins as conformationally constrained analogs of
      cytotoxic diarylpentanoids: synthesis and biological activity.
AB  - A series of polyoxygenated cinnamoylcoumarins was synthesized as conformationally
      constrained analogs of cytotoxic diarylpentanoids. The title compounds were
      tested against the viability of human chronic myelogenous leukemia (K562), human
      acute lymphoblastic leukemia (MOLT-4) and human breast adenocarcinoma (MCF-7)
      cell lines by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide) assay. Among them, all 6- or 7-hydroxylated compounds 6a-h exhibited
      remarkable cytotoxic activity. Particularly, 7-hydroxycoumarin analog 6h showed
      good antiproliferative activity against all tested cell lines (IC50 values<=5.5
      MUM). The preliminary study with selected compounds 6e and 6f showed that
      reactivity towards mitochondrial thiol compounds cab be considered as cytotoxic
      mechanism of designed compounds. Furthermore, the antioxidant activity evaluation
      of synthesized compounds showed that hydroxylated compounds had antioxidative
      potential at higher concentrations.

PMID- 23973824
TI  - Preparation of betulinic acid derivatives by chemical and biotransformation
      methods and determination of cytotoxicity against selected cancer cell lines.
AB  - Several novel 2,4-dinitrophenylhydrazone betulinic acid derivatives have been
      prepared by chemical and biotransformation methods using fungi and carrot cells.
      Some compounds showed significant cytotoxicity and selectivity against some tumor
      cell lines. The most active, 3-[(2,4-dinitrophenyl)hydrazono]lup-(20R)-29
      oxolupan-28-oic acid, showed IC50 values between 1.76 and 2.51 MUM against five
      human cancer cell lines. The most selective, 3-hydroxy-20-[(2,4
      dinitrophenyl)hydrazono]-29-norlupan-28-oic acid, was five to seven times more
      selective for cancer cells when compared to fibroblasts. Cell cycle analysis and
      apoptosis induction were studied for the most active derivatives. 

PMID- 23973823
TI  - Synthesis, characterization and biological activity of three square-planar
      complexes of Ni(II) with ethyl (2E)-2-[2
      (diphenylphosphino)benzylidene]hydrazinecarboxylate and monodentate
      pseudohalides.
AB  - Three square-planar complexes of nickel(II) with the tridentate condensation
      derivative of 2-(diphenylphosphino)benzaldehyde and ethyl carbazate, and
      monodentate pseudohalides, have been synthesized. Their crystal structures have
      been determined. All the complexes showed a significant antifungal activity,
      while only the azido complex displayed antibacterial activity. All the complexes
      were cytotoxic to a panel of six tumor cell lines, the azido complex showing a
      similar activity as cisplatin to leukemia cell line K562 and lower toxicity to
      normal MRC-5 cells than that anticancer agent. The complexes interfered with cell
      cycle of tumor cells and induced plasmid DNA cleavage. 

PMID- 23973825
TI  - Demonic axe-like conjugated alkynes in combating microbes.
AB  - A new series of disubstituted alkynes was obtained by microwave induced internal
      splitting of the corresponding beta-oxo-alkylidenetriphenylphosphoranes. The
      antimicrobial potential of these conjugated alkynes and phosphoranes was assayed
      in vitro against three Gram-positive bacteria (Staphylococcus aureus, Bacillus
      subtilis, Staphylococcus epidermidis), three Gram-negative bacteria (Escherichia
      coli, Pseudomonas aeruginosa, Klebsiella pneumoniae) and five fungal strains
      (Aspergillus niger, Candida albicans, Aspergillus flavus, Candida rugosa,
      Saccharomyces cerevisiae). The 3-pyridylalkyne derivatives viz., 3-(6
      chloropyridin-3-yl)propynenitrile (6a), 3-(2-chloropyridin-3-yl)propynenitrile
      (6b), ethyl 3-(6-chloropyridin-3-yl)propiolate (6c), iso-propyl 3-(6
      chloropyridin-3-yl)propiolate (6d) and 3-(2,6-dichloro-5-fluoropyridin-3
      yl)propynenitrile (6e) were found to be highly potent towards all tested
      microorganisms except E. coli. 

PMID- 23973826
TI  - Inhibition of the cardiac inward rectifier potassium currents by KB-R7943.
AB  - KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea) was developed as a
      specific inhibitor of the sarcolemmal sodium-calcium exchanger (NCX) with
      potential experimental and therapeutic use. However, KB-R7943 is shown to be a
      potent blocker of several ion currents including inward and delayed rectifier
      K(+) currents of cardiomyocytes. To further characterize KB-R7943 as a blocker of
      the cardiac inward rectifiers we compared KB-R7943 sensitivity of the background
      inward rectifier (IK1) and the carbacholine-induced inward rectifier (IKACh)
      currents in mammalian (Rattus norvegicus; rat) and fish (Carassius carassius;
      crucian carp) cardiac myocytes. The basal IK1 of ventricular myocytes was blocked
      with apparent IC50-values of 4.6*10(-6) M and 3.5*10(-6) M for rat and fish,
      respectively. IKACh was almost an order of magnitude more sensitive to KB-R7943
      than IK1 with IC50-values of 6.2*10(-7) M for rat and 2.5*10(-7) M for fish. The
      fish cardiac NCX current was half-maximally blocked at the concentration of 1.9
      3*10(-6) M in both forward and reversed mode of operation. Thus, the sensitivity
      of three cardiac currents to KB-R7943 block increases in the order
      IK1~INCX<IKACh. Therefore, the ability of KB-R7943 to block inward rectifier
      potassium currents, in particular IKACh, should be taken into account when
      interpreting the data with this inhibitor from in vivo and in vitro experiments
      in both mammalian and fish models.

PMID- 23973827
TI  - Modulation of lipocalin-type prostaglandin D2 synthase expression in catfish
      seminal vesicles by thyroid disrupting agents and hormones.
AB  - Thyroid hormones play crucial role in several biological processes including
      reproduction. Disruption of normal thyroid status by environmental contaminants
      can cause severe impairment in reproductive functions. In our previous study, we
      reported down-regulation of a protein in seminal vesicular fluid of air-breathing
      catfish, Clarias gariepinus during experimentally induced hyperthyroidism. N
      terminal amino acid sequence analysis followed by search in sequence database
      denoted it to be lipocalin-type prostaglandin D2 synthase (ptgds-b). In the
      present study, we cloned full-length cDNA of ptgds-b based on the N-terminal
      amino acid sequence. Surprisingly, Northern blot as well as RT-PCR analysis
      demonstrated the presence of ptgds-b transcript predominantly in seminal vesicles
      and developing testis. Further, ptgds-b mRNA significantly decreased in seminal
      vesicles following L-thyroxine overdose while there was an increased expression
      of ptgds-b after depletion of thyroid hormone by thiourea and withdrawal of the
      treatments reverted this effect. Treatment of catfish with human chorionic
      gonadotropin and estradiol significantly reduced ptgds-b expression. Taken
      together, we report ptgds-b as a thyroid hormone regulated protein in the seminal
      vesicles in addition to gonadotropin and estradiol. Further studies might explain
      the exclusive presence of ptgds-b in seminal vesicles and developing testis yet
      present data evaluated it as a putative biomarker for thyroid hormone disruption.

PMID- 23973828
TI  - Inactivation of internalized and surface contaminated enteric viruses in green
      onions.
AB  - With increasing outbreaks of gastroenteritis associated with produce, it is
      important to assess interventions to reduce the risk of illness. UV, ozone and
      high pressure are non-thermal processing technologies that have potential to
      inactivate human pathogens on produce and allow the retention of fresh-like
      organoleptic properties. The objective of this study was to determine if UV,
      ozone, and high pressure are effective technologies compared to traditional
      chlorine spray on green onions to reduce enteric viral pathogens and to determine
      the effect of location of the virus (surface or internalized) on the efficacy of
      these processes. Mature green onion plants were inoculated with murine norovirus
      (MNV), hepatitis A virus (HAV) and human adenovirus type 41 (Ad41) either on the
      surface through spot inoculation or through inoculating contaminated hydroponic
      solution allowing for uptake of the virus into the internal tissues. Inoculated
      green onions were treated with UV (240 mJ s/cm(2)), ozone (6.25 ppm for 10 min),
      pressure (500 MPa, for 5 min at 20 degrees C), or sprayed with calcium
      hypochlorite (150 ppm, 4 degrees C). Viral inactivation was determined by
      comparing treated and untreated inoculated plants using cell culture infectivity
      assays. Processing treatments were observed to greatly affect viral inactivation.
      Viral inactivation for all three viruses was greatest after pressure treatment
      and the lowest inactivation was observed after chlorine and UV treatment. Both
      surface inoculated viruses and viruses internalized in green onions were
      inactivated to some extent by these post-harvest processing treatments. These
      results suggest that ozone and high pressure processes aimed to reduce the level
      of microbial contamination of produce have the ability to inactivate viruses if
      they become localized in the interior portions of produce.

PMID- 23973829
TI  - Addition of ethanol to supercritical carbon dioxide enhances the inactivation of
      bacterial spores in the biofilm of Bacillus cereus.
AB  - Supercritical carbon dioxide (SC-CO2) was used to inactivate Bacillus cereus
      spores inside biofilms, which were grown on stainless steel. SC-CO2 treatment was
      tested using various conditions, such as pressure treatment (10-30 MPa),
      temperature (35-60 degrees C), and time (10-120 min). B. cereus vegetative cells
      in the biofilm were completely inactivated by treatment with SC-CO2 at 10 MPa and
      at 35 degrees C for 5 min. However, SC-CO2 alone did not inactivate spores in
      biofilm even after the treatment time was extended to 120 min. When ethanol was
      used as a cosolvent with SC-CO2 in the SC-CO2 treatment using only 2-10 ml of
      ethanol in 100ml of SC-CO2 vessel for 60-90 min of treatment time at 10 MPa and
      60 degrees C, B. cereus spores in the biofilm were found to be completely
      inactivated in the colony-forming test. We also assessed the viability of SC-CO2
      treated bacterial spores and vegetative cells in the biofilm by staining with
      SYTO 9 and propidium iodide. The membrane integrity of the vegetative cells was
      completely lost, while the integrity of the membrane was still maintained in most
      spores. However, when SC-CO2 along with ethanol was used, both vegetative cells
      and spores lost their membrane integrity, indicating that the use of ethanol as a
      cosolvent with SC-CO2 is efficient in inactivating the bacterial spores in the
      biofilm.

PMID- 23973830
TI  - Multiplex TaqMan(r) detection of pathogenic and multi-drug resistant Salmonella.
AB  - Overuse of antibiotics in the medical and animal industries is one of the major
      causes for the development of multi-drug-resistant (MDR) food pathogens that are
      often difficult to treat. In the past few years, higher incidences of outbreaks
      caused by MDR Salmonella have been increasingly documented. The objective of this
      study was to develop a rapid multiplex real-time polymerase chain reaction (PCR)
      assay for simultaneous detection of pathogenic and MDR Salmonella spp. A
      multiplex TaqMan(r)real-time PCR was designed by targeting the invasin virulence
      gene (invA), and four commonly found antibiotic resistance genes, viz.
      ampicillin, chloramphenicol, streptomycin and tetracycline. To avoid false
      negative results and to increase the reliability of the assay, an internal
      amplification control (IAC) was added which was detected using a locked nucleic
      acid (LNA) probe. In serially diluted (5 ng-50 fg) DNA samples, the assay was
      able to detect 100 genomic equivalents of Salmonella, while in a multiplex
      format, the sensitivity was 1000 genomic equivalents. The assay performed equally
      well on artificially contaminated samples of beef trim, ground beef of different
      fat contents (73:27, 80:20, 85:15 and 93:7), chicken rinse, ground chicken,
      ground turkey, egg, spinach and tomato. While the detection limit for un-enriched
      inoculated food samples was 10(4) CFU/g, this was improved to 10 CFU/g after a 12
      h enrichment in buffered peptone water, with 100% reproducibility. The multiplex
      real-time assay developed in this study can be used as a valuable tool to detect
      MDR virulent Salmonella, thus enhancing the safety of food.

PMID- 23973831
TI  - Emergence of pulsed electric fields resistance in Salmonella enterica serovar
      Typhimurium SL1344.
AB  - In this investigation we selected and isolated a culture derived from Salmonella
      enterica serovar Typhimurium SL1344 with stable increased resistance to pulsed
      electric fields (PEF) after repeated rounds of PEF treatment and outgrowth of
      survivors. The resulting culture showed a higher resistance to PEF treatments
      under different treatment conditions. The acquisition of PEF resistance was only
      observed in stationary phase cells. The cytoplasmic membrane of the resistant
      variant showed a higher resilience against PEF treatments, since a lower
      permeabilization degree was observed after PEF treatments, in comparison to the
      parental strain. Resistance to PEF was also accompanied by a higher tolerance to
      acidic pH, hydrogen peroxide and ethanol, but not to heat. The occurrence of a
      PEF resistant variant in S. enterica serovar Typhimurium SL1344 emphasizes the
      need to further study the mechanisms of inactivation and resistance by PEF for an
      adequate design of safe treatments. 

PMID- 23973832
TI  - Salmonella on feces, hides and carcasses in beef slaughter facilities in
      Venezuela.
AB  - This study determined Salmonella prevalence at different stages during the
      slaughtering in three beef slaughter plants (A, B and C) located in the western
      region of Venezuela (Zulia and Lara states). Each facility was visited three
      times at monthly intervals, from the months October through December of 2006.
      Samples were collected from hides (n=80), fecal grabs (n=80) and carcasses (n=80)
      at the phases of pre-evisceration, after-evisceration and pre-cooler at three
      sampling sites on the animals (rump, flank and brisket). Salmonella prevalence
      was higher on hides (36.3%) than on feces (13.8%) (P<0.05). Differences among
      slaughter plants for overall Salmonella prevalence were observed (P=0.001; A:
      3.5%, B: 11.1%, C: 4.4%). From the isolated strains, Salmonella enterica
      subspecies enterica ser. Saintpaul, Salmonella ser. Javiana and Salmonella ser.
      Weltevreden were identified. Cattle feces and hides might be considered as
      important sources of Salmonella for carcass contamination at different slaughter
      stages. The presence of potentially pathogenic Salmonella serotypes at the
      slaughtering stages is an evidence of the circulation of this pathogen in the
      food environment; its presence could increase consumers' risks of infection if
      proper food handling and preparation techniques are not followed. These data
      should serve as a baseline for future comparisons in Salmonella prevalence on
      beef carcasses to be used by the government and industry in order to establish
      preventive measures and to better address the risks of Salmonella contamination. 

PMID- 23973833
TI  - Prediction of Salmonella carcass contamination by a comparative quantitative
      analysis of E. coli and Salmonella during pig slaughter.
AB  - Faecal contamination of carcasses in the slaughterhouse is generally considered
      to be the source of Salmonella on pork. In this study the hygiene indicator
      Escherichia coli is used to quantify faecal contamination of carcasses and it is
      hypothesized that it can be used to predict the quantitative carcass
      contamination with Salmonella, when the distribution of Salmonella concentrations
      in faeces is known. Paired pig sample data (faecal samples and carcass swabs)
      were obtained from five slaughterhouses and analysed for prevalence and
      concentrations of E. coli and Salmonella. A simple model was developed to
      describe the faecal contamination of carcasses using the E. coli data. The E.
      coli results suggested different hygiene performances in different
      slaughterhouses, and showed that a model assuming that carcasses are
      predominantly contaminated by their own faeces was not appropriate. Observed
      Salmonella prevalences were low (on average 1.9% on carcasses) and between
      slaughterhouses the prevalences ranked differently than the hygiene performance
      based on the E. coli data suggested. Also, the Salmonella concentrations
      predicted using E. coli as a faecal indicator were lower than the observed
      Salmonella concentrations. It is concluded that the faecal carriage of Salmonella
      together with the faecal contamination of carcasses, as predicted from E. coli
      data in the animal faeces and hygiene performance of the slaughterhouse, is not
      sufficient to explain carcass contamination with Salmonella. Our extensive data
      set showed that other factors than the observed faecal carriage of Salmonella by
      the individual animals brought to slaughter, play a more important role in the
      Salmonella carcass contamination of pork. 

PMID- 23973834
TI  - Reduction of the degradation activity of umami-enhancing purinic ribonucleotide
      supplement in miso by the targeted suppression of acid phosphatases in the
      Aspergillus oryzae starter culture.
AB  - Miso (fermented soybean paste) is a traditional Japanese fermented food, and is
      now used worldwide. The solid-state culture of filamentous fungus, Aspergillus
      oryzae, grown on rice is known as rice-koji, and is important as a starter for
      miso fermentation because of its prominent hydrolytic enzyme activities.
      Recently, commercial miso products have been supplemented with purinic
      ribonucleotides, such as inosine monophosphate (IMP) and guanine monophosphate,
      to enhance the characteristic umami taste of glutamate in miso. Because the
      purinic ribonucleotides are degraded by enzymes such as acid phosphatases in
      miso, heat inactivation is required prior to the addition of these flavorings.
      However, heat treatment is a costly process and reduces the quality of miso.
      Therefore, an approach to lower acid phosphatase activities in koji culture is
      necessary. Transcriptional analysis using an A. oryzae KBN8048 rice-koji culture
      showed that eight of the 13 acid phosphatase (aph) genes were significantly down
      regulated by the addition of phosphoric acid in the preparation of the culture in
      a concentration-dependent manner, while aphC expression was markedly up-regulated
      under the same conditions. The eight down-regulated genes might be under the
      control of the functional counterpart of the Saccharomyces cerevisiae
      transcriptional activator Pho4, which specifically regulates phosphatase genes in
      response to the ambient phosphate availability. However, the regulatory mechanism
      of aphC was not clear. The IMP dephosphorylation activities in rice-koji cultures
      of KBN8048 and the aphC deletion mutant (DeltaaphC) were reduced by up to 30% and
      70%, respectively, in cultures with phosphoric acid, while protease and amylase
      activity, which is important for miso fermentation, was minimally affected. The
      miso products fermented using the rice-koji cultures of KBN8048 and DeltaaphC
      prepared with phosphoric acid had reductions in IMP dephosphorylation activity of
      80% and 90%, respectively, without any adverse effects on amylase and protease
      activities. Thus, preparing the A. oryzae rice-koji culture under phosphate
      sufficient conditions preferentially produces a fermentation starter of miso
      exhibiting low purinic ribonucleotide dephosphorylation activity. Moreover, aphC
      is a potential breeding target to reduce purinic ribonucleotide degradation
      activity further in commercial miso products. 

PMID- 23973835
TI  - Norovirus contamination on French marketed oysters.
AB  - Contaminated shellfish have been implicated in gastroenteritis outbreaks in
      different countries. As no regulation has been set up yet regarding viral
      contamination of food, very few data are available on the prevalence of
      contaminated products on the market. This study presents data obtained from
      oysters collected on the French market in one producing area over a 16 month
      period of time. Noroviruses were detected in 9% of samples with a seasonal impact
      and influence of climatic events. Contamination levels were low and,
      surprisingly, oysters sampled directly from the producer were found to have less
      contamination than oysters from supermarkets.

PMID- 23973836
TI  - Comparative efficacy of Zataria multiflora Boiss., Origanum compactum and Eugenia
      caryophyllus essential oils against E. coli O157:H7, feline calicivirus and
      endogenous microbiota in commercial baby-leaf salads.
AB  - Ready-to-eat salads using baby-leaf and multi-leaf mixes are one of the most
      promising developments in the fresh-cut food industry. There is great interest in
      developing novel decontamination treatments, which are both safe for consumers
      and more efficient against foodborne pathogens. In this study, emulsions of
      essential oils (EOs) from Origanum compactum (oregano), Eugenia caryophyllus
      (clove), and Zataria multiflora Boiss (zataria) were applied by spray (0.8 ml)
      after the sanitizing washing step. The aim was to investigate their ability to
      control the growth of potentially cross-contaminating pathogens and endogenous
      microbiota in commercial baby leaves, processed in a fresh-cut produce company.
      Zataria EO emulsions of 3%, 5% and 10% reduced Escherichia coli O157:H7 by 1.7,
      2.2 and 3.5 log cfu/g in baby-leaf salads after 5 days of storage at 7 degrees C.
      By contrast, reductions in E. coli O157:H7 counts remained the same when clove
      was applied at concentrations of 5% and 10% (2.5 log cfu/g reduction). Oregano
      (10%) reduced inoculated E. coli O157:H7 counts in baby-leaf salads by a maximum
      of 0.5 log cfu/g after 5 days of storage. Zataria showed strong antimicrobial
      efficacy against E. coli O157:H7 and also against the endogenous microbiota of
      baby-leaf salads stored for 9 days. Feline calicivirus (FCV), a norovirus
      surrogate, survived on inoculated baby-leaf salads during refrigerated storage (9
      days at 7 degrees C) regardless of treatment. Refrigeration temperatures
      completely annulled the effectiveness of the EOs against FCV inoculated in baby
      leaf salads as occurred in FCV cultures. This study shows that EOs, and zataria
      in particular, have great potential use as an additional barrier to reduce
      contamination-related risks in baby-leaf salads. However, further research should
      be done into foodborne viruses in order to improve food safety.

PMID- 23973837
TI  - Presence of Clostridium difficile in pigs and cattle intestinal contents and
      carcass contamination at the slaughterhouse in Belgium.
AB  - The objective of this study was to evaluate the presence of Clostridium difficile
      in intestinal and carcass samples collected from pigs and cattle at a single
      slaughterhouse. C. difficile was isolated in 1% and 9.9% of the pig and cattle
      intestinal contents and in 7.9% and 7% of cattle and pig carcass samples
      respectively. A total of 19 different PCR-ribotypes were identified, among them
      types 078 and 014. Seven of 19 ribotypes correlated with the PCR-ribotypes
      involved in human C. difficile infections in Belgium. This study confirms that
      animals are carriers of C. difficile at slaughter and ribotypes are identical
      than those in humans, and that carcass contamination occurs inside the
      slaughterhouse. 

PMID- 23973838
TI  - Influence of temperature and substrate conditions on the omt-1 gene expression of
      Aspergillus parasiticus in relation to its aflatoxin production.
AB  - Most strains of Aspergillus parasiticus are able to produce high concentrations
      of aflatoxin (AF) B1 and G1 which are among the most potent mutagenic,
      teratogenic, and carcinogenic mycotoxins. Molecular studies in relation to
      activity of secondary metabolite gene clusters are crucial to improving food
      safety. In the present work, reverse transcriptase quantitative PCR (RT-qPCR) was
      used to monitor the influence of temperature, substrates containing nitrogen and
      incubation time on the omt-1 gene expression in A. parasiticus. Phenotypic AFB1
      and G1 production was also evaluated by high-performance liquid chromatography
      mass spectrometry (HPLC-MS). The results demonstrated that temperature (25
      degrees C and 30 degrees C) influenced relative expression of omt-1 gene
      throughout the time (maximum at 25 degrees C) while substrate composition was not
      affected by it. However, when effect of temperature and substrate was analyzed at
      each incubation time, significant effects were found. Optimal conditions for
      biosynthesis of AFB1 and AFG1 were similar, and they were related to changes in
      temperature and sodium nitrate. The highest AFB1 and G1 production levels were
      found at 25 degrees C. However, lower AFB1 and G1 values were obtained when A.
      parasiticus grew on the substrate containing sodium nitrate and there was no
      production of these AFs at 37 degrees C in any of the conditions tested. In
      addition, omt-1 gene expression was correlated to AFB1 and G1 syntheses at the
      different conditions. Use of temperature conditions and sodium nitrate
      concentrations which limit production of AFs holds potential for preventing AF
      from entering the food chain. 

PMID- 23973839
TI  - Characterization of aerobic spore-forming bacteria associated with industrial
      dairy processing environments and product spoilage.
AB  - Due to changes in the design of industrial food processing and increasing
      international trade, highly thermoresistant spore-forming bacteria are an
      emerging problem in food production. Minimally processed foods and products with
      extended shelf life, such as milk products, are at special risk for contamination
      and subsequent product damages, but information about origin and food quality
      related properties of highly heat-resistant spore-formers is still limited.
      Therefore, the aim of this study was to determine the biodiversity, heat
      resistance, and food quality and safety affecting characteristics of aerobic
      spore-formers in the dairy sector. Thus, a comprehensive panel of strains
      (n=467), which originated from dairy processing environments, raw materials and
      processed foods, was compiled. The set included isolates associated with recent
      food spoilage cases and product damages as well as isolates not linked to product
      spoilage. Identification of the isolates by means of Fourier-transform infrared
      spectroscopy and molecular methods revealed a large biodiversity of spore
      formers, especially among the spoilage associated isolates. These could be
      assigned to 43 species, representing 11 genera, with Bacillus cereus s.l. and
      Bacillus licheniformis being predominant. A screening for isolates forming
      thermoresistant spores (TRS, surviving 100 degrees C, 20 min) showed that about
      one third of the tested spore-formers was heat-resistant, with Bacillus subtilis
      and Geobacillus stearothermophilus being the prevalent species. Strains producing
      highly thermoresistant spores (HTRS, surviving 125 degrees C, 30 min) were found
      among mesophilic as well as among thermophilic species. B. subtilis and Bacillus
      amyloliquefaciens were dominating the group of mesophilic HTRS, while Bacillus
      smithii and Geobacillus pallidus were dominating the group of thermophilic HTRS.
      Analysis of spoilage-related enzymes of the TRS isolates showed that mesophilic
      strains, belonging to the B. subtilis and B. cereus groups, were strongly
      proteolytic, whereas thermophilic strains displayed generally a low enzymatic
      activity and thus spoilage potential. Cytotoxicity was only detected in B.
      cereus, suggesting that the risk of food poisoning by aerobic, thermoresistant
      spore-formers outside of the B. cereus group is rather low.

PMID- 23973840
TI  - Modeling the influence of temperature, water activity and water mobility on the
      persistence of Salmonella in low-moisture foods.
AB  - Salmonella can survive in low-moisture foods for long periods of time. Reduced
      microbial inactivation during heating is believed to be due to the interaction of
      cells and water, and is thought to be related to water activity (a(w)). Little is
      known about the role of water mobility in influencing the survival of Salmonella
      in low-moisture foods. The aim of this study was to determine how the physical
      state of water in low-moisture foods influences the survival of Salmonella and to
      use this information to develop mathematical models that predict the behavior of
      Salmonella in these foods. Whey protein powder of differing water mobilities was
      produced by pH adjustment and heat denaturation, and then equilibrated to aw
      levels between 0.19+/-0.03 and 0.54+/-0.02. Water mobility was determined by wide
      line proton-NMR. Powders were inoculated with a four-strain cocktail of
      Salmonella, vacuum-sealed and stored at 21, 36, 50, 60, 70 and 80 degrees C.
      Survival data was fitted to the log-linear, the Geeraerd-tail, the Weibull, the
      biphasic-linear and the Baranyi models. The model with the best ability to
      describe the data over all temperatures, water activities and water mobilities
      (f(test)<F(table)) was selected for secondary modeling. The Weibull model
      provided the best description of survival kinetics for Salmonella. The influence
      of temperature, aw and water mobility on the survival of Salmonella was evaluated
      using multiple linear regression. Secondary models were developed and then
      validated in dry non-fat dairy and grain, and low-fat peanut and cocoa products
      within the range of the modeled data. Water activity significantly influenced the
      survival of Salmonella at all temperatures, survival increasing with decreasing
      a(w). Water mobility did not significantly influence survival independent of
      a(w). Secondary models were useful in predicting the survival of Salmonella in
      various low-moisture foods providing a correlation of R=0.94 and an acceptable
      prediction performance of 81%. The % bias and % discrepancy results showed that
      the models were more accurate in predicting survival in non-fat food systems as
      compared to foods containing low-fat levels (12% fat). The models developed in
      this study represent the first predictive models for survival of Salmonella in
      low-moisture foods. These models provide baseline information to be used for
      research on risk mitigation strategies for low-moisture foods.

PMID- 23973841
TI  - Evaluation of lactic acid bacteria and yeast diversity in traditional white
      pickled and fresh soft cheeses from the mountain regions of Serbia and lowland
      regions of Croatia.
AB  - The goal of this study was the characterisation of indigenous lactic acid
      bacteria (LAB) and yeasts isolated from nine white pickled (BG) and nine fresh
      soft (ZG) artisanal cheeses collected in Serbia and Croatia. While LAB were
      present in all of the cheeses collected, yeasts were found in all BG cheeses but
      only in three ZG cheese samples. High LAB and yeast species diversity was
      determined (average H'(L)=0.4 and H'(Y)=0.8, respectively). The predominant LAB
      species in white pickled (BG) cheeses were Lactococcus lactis, Lactobacillus
      plantarum, and Leuconostoc mesenteroides, while in fresh soft (ZG) cheeses the
      most dominant LAB species were L. lactis, Enterococcus faecalis, and Leuconostoc
      pseudomesenteroides. Among the 20 yeast species found, Debaryomyces hansenii,
      Candida zeylanoides, and Torulaspora delbrueckii were found to be predominant in
      BG cheeses, while Yarrowia lipolytica was predominant in ZG cheeses. The
      characterisation of metabolic and technological potentials revealed that 53.4% of
      LAB isolates produced antimicrobial compounds, 44.3% of LAB strains showed
      proteolytic activity, while most of the yeast species possessed either lipolytic
      or proteolytic activity. In conclusion, the results obtained in this study showed
      that the composition of LAB and yeast populations in white pickled and fresh soft
      cheeses is region specific. The knowledge gained in this study could eventually
      be used to select region specific LAB and yeast strains for the production of
      white pickled and fresh soft artisanal cheeses with geographically specific
      origins under controlled conditions.

PMID- 23973842
TI  - Aeromonas spp. simultaneously harbouring bla(CTX-M-15), bla(SHV-12), bla(PER-1)
      and bla(FOX-2), in wild-growing Mediterranean mussel (Mytilus galloprovincialis)
      from Adriatic Sea, Croatia.
AB  - Aeromonas species are becoming renowned as emerging pathogens by increasingly
      giving rise to a wide spectrum of food and waterborne infections in humans.
      Another worrisome feature of aeromonads is the growing frequency of antibiotic
      resistance as a consequence of their prominent diversity in terms of resistance
      determinants. This study aimed at determining the antimicrobial resistance
      pattern, prevalence and characterization of acquired beta-lactamases, including
      extended-spectrum-beta-lactamases (ESBLs) and AmpC cephalosporinases, as well as
      the presence of class 1 and 2 integrons, in Aeromonas isolates from wild-growing
      Mediterranean mussel (Mytilus galloprovincialis) of the eastern coast of Adriatic
      Sea, Croatia. Isolates were tested for susceptibility to 16 antibiotics and beta
      lactam/beta-lactamase inhibitor combinations. Cephalosporin-resistant isolates
      were further screened by PCR for genes encoding AmpC (bla(FOX), bla(CMY),
      bla(MOX), bla(LAT), bla(BIL), bla(DHA), bla(ACC), bla(MIR), bla(ACT)), ESBLs
      (bla(TEM), bla(SHV), bla(CTX-M), bla(PER), bla(VEB), bla(GES/IBC), bla(OXA)) and
      integrases (intI1, intI2, intI3). Location of bla genes was characterized by
      plasmid DNA fingerprinting and Southern blot hybridization. Plasmids carrying
      ESBL genes were investigated for transferability by conjugation and PCR-based
      replicon typed. Out of 147 Aeromonas isolates recovered, 30 (20%) demonstrated
      multiple resistance profile, with co-resistance most frequently detected against
      penicillins, piperacillin/sulbactam and tetracycline. ESBL-encoding genes were
      detected in 21 (13 Aeromonas caviae and 8 Aeromonas hydrophila) isolates, with
      bla(CTX-M-15) gene identified in 19 and bla(SHV-12) in 12 isolates. Among them,
      10 isolates simultaneously harboured bla(CTX-M-15) and bla(SHV-12), while 3
      isolates additionally carried an AmpC beta-lactamase bla(FOX-2) gene. bla(PER-1)
      gene was identified in a single isolate also harbouring the bla(CTX-M-15) gene.
      While bla(SHV-12) was chromosomally encoded, bla(CTX-M-15) was located on
      conjugative IncFIB-type plasmids of ~40 kb in A. caviae isolates. IntI1 and intI2
      genes were detected in 57.1% and 33.3% of ESBL-producing isolates. To the best
      our knowledge, this is the first report of environmental A. caviae isolates
      producing CTX-M-15, and isolation of SHV-12-producing A. hydrophila and A. caviae
      strains worldwide. This is also believed to be the first report of the FOX-2, CTX
      M-15 and SHV-12 simultaneous production in aeromonads, highlighting both the
      potential risk for human health, and a role of these foodborne pathogens as
      reservoirs of resistance determinants in coastal marine environment.

PMID- 23973843
TI  - An investigation of the immediate and storage effects of chemical treatments on
      Campylobacter and sensory characteristics of poultry meat.
AB  - Campylobacteriosis is the most common foodborne bacterial infection in developed
      countries and many cases are associated with poultry. This study investigated the
      immediate and storage effect of dipping inoculated poultry skin samples in
      trisodium phosphate (TSP, 10 & 14%, w/v), lactic acid (LA, 1 & 5%, v/v), citric
      acid (CA, 1 & 5%, w/v), peroxyacids (POA, 100 & 200 ppm) and acidified sodium
      chlorite (ASC, 500 & 1200 ppm). Spray application was also tested using the
      higher concentrations in the laboratory. In a broiler processing plant the
      efficacy of using TSP (14%) and CA (5%) applied by immersion and spray was
      investigated using naturally contaminated carcasses and the effect of these
      treatments on the sensory attributes of a skin-on (drumstick) and skin-off
      (fillet) raw and cooked product was assessed using descriptive sensory analysis.
      In the laboratory, immersion in TSP (14%), LA (5%), CA (5%) and ASC (1200 ppm)
      significantly (P<0.05) reduced the Campylobacter counts and a 2.5 to 3 log10
      cfu/cm(2) reduction was observed within the shelf-life (3-5 days) of poultry
      meat. Spraying was ineffective even after storage. In the broiler processing
      plant, immersion in TSP (14%) or CA (5%) achieved Campylobacter reductions of
      2.49 and 1.44 log10 cfu/cm(2), respectively. There were no significant
      differences between the treatments for any of the attributes measured in either
      raw or cooked drumsticks. The 'colour' of raw chicken fillets treated with both
      TSP (14%, w/v) and CA (5%, w/v) was significantly (P<=0.05) lighter than that of
      control samples. The 'intensity of chicken odour' and the perception of 'salt' in
      cooked chicken fillets treated with CA (5%, w/v) were also significantly
      (P<=0.05) higher than that of either control or TSP (14%, w/v) treated samples.
      It was concluded that TSP (14%) or CA (5%) could be applied to significantly
      reduce Campylobacter contamination of broilers without adversely affecting the
      sensory quality of the product.

PMID- 23973844
TI  - Identification and quantification of fungi and mycotoxins from Pu-erh tea.
AB  - Pu-erh tea originates from the province of Yunnan in south-western China. As this
      tea is produced by so called Aspergillus post-fermentation the question arises
      which molds and mycotoxins may be found in this tea. In total 36 samples of Pu
      erh tea were investigated for their content of filamentous fungi and the
      mycotoxins aflatoxins B1, B2, G1, and G2, fumonisins B1, B2, and B3, and
      ochratoxin A. Fungi were isolated from all samples in a concentration of
      1.0*10(1) to 2.6*10(6) colony forming units (cfu)/g tea, all together 19 fungal
      genera and 31 species were identified. The most prevalent species were
      Aspergillus acidus and Aspergillus fumigatus, followed by Zygomycetes and
      Penicillium species. Aflatoxins and fumonisins were not found in the samples
      investigated, ochratoxin A was detected in 4 of 36 teas (11.1%). 

PMID- 23973845
TI  - Dietary galactooligosaccharide affects intestinal microbiota, stress resistance,
      and performance of Caspian roach (Rutilus rutilus) fry.
AB  - The aim of this study was to assess the effects of galactooligosaccharide (GOS),
      on the growth performance, stress resistance and intestinal microbiota of Caspian
      roach (Rutilus rutilus) fry. Specimens (1.36 +/- 0.03 g) were fed either a basal
      control diet (0% GOS, non-supplemented) or the basal diet supplemented with 1%
      and 2% of GOS. After 7 weeks of the feeding trials, growth factors (final weight,
      weight gain, specific growth rate, condition factor and food conversion ratio) as
      well as body composition, resistance to salinity stress and autochthonous
      intestinal microbiota were assessed. Results demonstrated that at the end of the
      trial growth factors (final weight, weight gain, SGR, FCR) were significantly
      higher in 2% GOS fed fish (P < 0.05). In addition, supplementation of GOS
      significantly increased both survival rate (P < 0.05), and resistance to a
      salinity stress challenge of prebiotic fed groups (P < 0.05). However, body
      composition and the total autochthonous intestinal heterotrophic bacteria counts
      remained unaffected in different treatments (P > 0.05). Nevertheless,
      autochthonous lactic acid bacteria levels were significantly elevated in fish fed
      2% dietary GOS (P < 0.05). These results confirm that GOS improves growth
      performance, stress resistance and modulates intestinal microbiota by increasing
      lactic acid bacteria of Caspian roach fry, a very important fish species in the
      Caspian Sea.

PMID- 23973846
TI  - Effect of dietary supplementation of fructooligosaccharide (FOS) on growth
      performance, survival, lactobacillus bacterial population and hemato
      immunological parameters of stellate sturgeon (Acipenser stellatus) juvenile.
AB  - The dietary supplementation of fructooligosaccharide (FOS) in stellate sturgeon
      juvenile, Acipenser stellatus (with mean initial body weight of 30.16 +/- 0.14 g)
      was evaluated for the effect on growth, autochthonous intestinal microbiata and
      hemato-immunological parameters for 11 weeks. FOS was added at a level of 0, 1%
      and 2% to the commercial pellet diet (BioMar). At the end of the experiment,
      growth parameters, survival rate, lactobacillus bacterial population,
      hematological and immunological parameters were determined. The fish fed on 1%
      FOS significantly showed higher final weight, WG%, SGR and PER and lower FCR
      compared to those of the control group (P < 0.05). Survival rate did not
      significantly differ between the treatments (P > 0.05). However, FOS
      administration resulted in lower survival. The serum lysozyme activity was
      significantly affected by dietary 1% FOS (P < 0.05), while respiratory burst
      activity was not significantly affected by dietary treatments (P > 0.05). In fish
      fed on the diet with 1% FOS showed a significant increase of total heterotrophic
      autochthonous bacterial and presumptive LAB levels (P < 0.05) compared with those
      fed on the diets supplemented with prebiotics. In addition to increase in WBC,
      RBC, MCV, hematocrit, hemoglobin and lymphocyte levels were observed in this
      group. These results indicated that dietary supplementation of FOS at a dose of
      1% improved growth performance, beneficial intestinal microbiata and stimulate
      immune response of stellate sturgeon juvenile. 

PMID- 23973847
TI  - Evidences for the involvement of an invertebrate goose-type lysozyme in disk
      abalone immunity: cloning, expression analysis and antimicrobial activity.
AB  - Lysozymes are ubiquitously distributed enzymes with hydrolytic activity against
      bacterial peptidoglycan and function to protect organisms from microbial
      pathogens. In this study, an invertebrate goose-type lysozyme, designated as
      abLysG, was identified in the disk abalone, Haliotis discus discus. The full
      length cDNA of abLysG was 894 bp in length with an open reading frame of 789 bp
      encoding a polypeptide of 263 amino acids containing a signal peptide and a
      characteristic soluble lytic transglycosylase domain. Six cysteine residues and
      two catalytic residues (Glu(142) and Asp(168)) conserved among molluscs were also
      identified. The 3D homology structural models of abLysG and hen egg white
      lysozyme had similar conformations of the active sites involved in the binding of
      substrate. BAC sequence data revealed that the genomic structure of disk abalone
      g-type lysozyme comprises 7 exons with 6 intervening introns. The deduced amino
      acid sequence of abLysG shared 45.2-61.6% similarity with those of other molluscs
      and vertebrates. The TFSEARCH server predicted a variety of transcription factor
      binding sites in the 5'-flanking region of the abLysG gene, some of which are
      involved in transcriptional regulation of the lysozyme gene. abLysG expression
      was detected in multiple tissues with the highest expression in mantle. Moreover,
      qPCR analysis of abLysG mRNA expression demonstrated significant up-regulation in
      gill in response to infection by live bacteria (Vibrio parahaemolyticus and
      Listeria monocytogenes), virus (viral hemorrhagic septicemia) and bacterial
      mimics (LPS and PGN). Expression of the recombinant disk abalone g-type lysozyme
      in Escherichia coli BL21, demonstrated its bacteriolytic activity against several
      Gram-negative and Gram-positive bacterial species. Collectively these data
      suggest that abLysG is an antimicrobial enzyme with a potential role in the disk
      abalone innate immune system to protect it from bacterial and viral infections.

PMID- 23973848
TI  - Proton pump inhibitors as also inhibitors of atrial fibrillation.
AB  - Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related
      upper digestive diseases, including gastric and duodenal ulcer and
      gastroesophageal reflux disease (GERD). Remarkably, several small clinical trials
      have shown that these drugs also reduce the symptoms and frequency of atrial
      fibrillation (AF) episodes in patients treated for comorbid acid reflux. Although
      the mechanism remains unclear, the effect might pinpoint a connection between
      GERD and AF. To this end, it is known that both oxidants and inflammation affect
      initiation and maintenance of AF, and PPIs may reduce symptoms and frequency of
      AF episodes through their antioxidant and anti-inflammatory effects. This review
      focuses on the anti-AF effects of PPIs beyond their inhibition of gastric acid
      production.

PMID- 23973849
TI  - Preventing variceal bleeding in infants and children: is less more?

PMID- 23973850
TI  - NAFLD fibrosis score: is it ready for wider use in clinical practice and for
      clinical trials?

PMID- 23973851
TI  - Reply: To PMID 23622138.

PMID- 23973853
TI  - Is there still a role for thiopurines in Crohn's disease?

PMID- 23973854
TI  - Bone health guidelines for patients with chronic pancreatitis.

PMID- 23973855
TI  - Is the gap between the developed and developing countries in the incidence of
      inflammatory bowel disease disappearing?

PMID- 23973856
TI  - Reply: To PMID 23583432.

PMID- 23973857
TI  - Odynophagia after upper endoscopy: an unusual finding.

PMID- 23973858
TI  - Bacterial translocation influences the response to biological therapy in Crohn's
      disease.

PMID- 23973859
TI  - Assessment of radioligands for PET imaging of cyclooxygenase-2 in an ischemic
      neuronal injury model.
AB  - Cyclooxygenase-2 (COX-2) plays crucial roles in progressive neuronal death in
      ischemic brain injury. In the present study, we evaluated two radiolabeled COX-2
      selective inhibitors, [11C]celecoxib and [11C]rofecoxib, as positron emission
      tomography (PET) tracers for COX-2 imaging in normal and ischemic mouse brains.
      We also took advantage of our newly-generated antibody highly selective for mouse
      COX-2 to prove accumulation of the radioligands in regions enriched with COX-2.
      In vitro autoradiography demonstrated specific binding of high-concentration
      [11C]rofecoxib but not [11C]celecoxib to the cerebellum and brain stem of normal
      brains wherein COX-2 immunoreactivity in neurons was most abundantly observed.
      Meanwhile, both of these radioligands failed to detect COX-2 expression in PET
      assays despite their excellent brain permeability. Hypoperfusion-induced ischemia
      caused marked necrotic neuron death accompanied by gliosis and enhancement of
      neuronal COX-2 immunoreactivity in the hippocampus. Correspondingly, in vitro
      autoradiographic binding of [11C]rofecoxib was increased in the injured
      hippocampus compared to the uninjured contralateral region, but failed in living
      brains of ischemia model likewise. Our work provides the rationale for monitoring
      COX-2 as a biomarker reflecting ischemic brain injuries and demonstrates that
      [11C]rofecoxib, not [11C]celecoxib, is useful for in vitro assays of COX-2, but
      its affinity would be insufficient for in vivo PET visualization.

PMID- 23973860
TI  - Deposition of collagen IV and aggrecan in leptomeningeal arteries of hereditary
      brain haemorrhage with amyloidosis.
AB  - Hereditary Cystatin C Amyloid Angiopathy (HCCAA) is a rare genetic disease in
      Icelandic families caused by a mutation in the cystatin C gene, CST3. HCCAA is
      classified as a cerebral amyloid angiopathy and mutant cystatin C forms amyloid
      deposits in cerebral arteries resulting in fatal haemorrhagic strokes in young
      adults. The aetiology of HCCAA pathology is not clear and there is, at present,
      no animal model of the disease. The aim of this study was to increase
      understanding of the cerebral vascular pathology of HCCAA patients with an
      emphasis on structural changes within the arterial wall of affected
      leptomeningeal arteries. Examination of post-mortem samples revealed extensive
      changes in the walls of affected arteries characterised by deposition of
      extracellular matrix constituents, notably collagen IV and the proteoglycan
      aggrecan. Other structural abnormalities were thickening of the laminin
      distribution, intimal thickening concomitant with a frayed elastic layer, and
      variable reduction in the integrity of endothelia. Our results show that excess
      deposition of extracellular matrix proteins in cerebral arteries of HCCAA is a
      prominent feature of the disease and may play an important role in its
      pathogenesis. 

PMID- 23973861
TI  - The extent and the nature of the cholinergic contribution to the hepatic
      encephalopathy-induced cognitive impairment.

PMID- 23973863
TI  - Apelin and copeptin: two opposite biomarkers associated with kidney function
      decline and cyst growth in autosomal dominant polycystic kidney disease.
AB  - Vasopressin (AVP) plays a detrimental role in autosomal dominant polycystic
      kidney disease (ADPKD). Copeptin represents a measurable substitute for
      circulating AVP whereas apelin counteracts AVP signaling. The aim of this study
      was to investigate the predictive value of apelin and copeptin for the
      progression of ADPKD disease. 52 ADPKD patients were enrolled and followed until
      the end of the observation period or the primary study endpoint was reached,
      defined by the combined outcome of decrease of glomerular filtration rate
      associated with a total renal volume increase. Receiver operating characteristics
      (ROC) analysis was employed for identifying the progression of renal disease and
      Kaplan-Meier curves assessed the renal survival. Adjusted risk estimates for
      progression endpoint and incident renal replacement therapy (RRT) were calculated
      using Cox proportional hazard regression analysis. ADPKD patients were
      characterized by lower apelin levels and higher copeptin levels when compared
      with healthy subjects. These biomarkers were strictly correlated with osmolality
      and markers of renal function. At ROC analysis, apelin and copeptin showed a very
      good diagnostic profile in identifying ADPKD progression. After the follow up of
      24 months, 33 patients reached the endpoint. Cox proportional hazard regression
      analysis showed that apelin predicted renal disease progression and incident RRT
      independently of other potential confounders. Apelin is associated with kidney
      function decline in ADPKD, suggesting that it may be a new marker to predict
      kidney outcome. 

PMID- 23973862
TI  - Redox-sensitive glycogen synthase kinase 3beta-directed control of mitochondrial
      permeability transition: rheostatic regulation of acute kidney injury.
AB  - Mitochondrial dysfunction plays a pivotal role in necroapoptotic cell death and
      in the development of acute kidney injury (AKI). Evidence suggests that glycogen
      synthase kinase (GSK) 3beta resides at the nexus of multiple signaling pathways
      implicated in the regulation of mitochondrial permeability transition (MPT). In
      cultured renal tubular epithelial cells, a discrete pool of GSK3beta was detected
      in mitochondria. Coimmunoprecipitation assay confirmed that GSK3beta physically
      interacts with cyclophilin F and voltage-dependent anion channel (VDAC), key MPT
      regulators that possess multiple GSK3beta phosphorylation consensus motifs,
      suggesting that GSK3beta has a direct control of MPT. Upon a strong burst of
      reactive oxygen species elicited by the pro-oxidant herbicide paraquat, the
      activity of the redox-sensitive GSK3beta was drastically enhanced. This was
      accompanied by augmented phosphorylation of cyclophilin F and VDAC, associated
      with MPT and cell death. Inhibition of GSK3beta by either the selective inhibitor
      4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) or forced expression
      of a kinase-dead mutant obliterated paraquat-induced phosphorylation of
      cyclophilin F and VDAC, prevented MPT, and improved cellular viability.
      Conversely, ectopic expression of a constitutively active GSK3beta amplified the
      effect of paraquat on cyclophilin F and VDAC phosphorylation and sensitized cells
      to paraquat-induced MPT and death. In vivo, paraquat injection elicited marked
      oxidant stress in the kidney and resulted in acute kidney dysfunction and massive
      tubular apoptosis and necrosis. Consistent with in vitro findings, the activity
      of GSK3beta was augmented in the kidney after paraquat injury, associated with
      increased phosphorylation of cyclophilin F and VDAC and sensitized MPT. TDZD-8
      blocked GSK3beta activity in the kidney, intercepted cyclophilin F and VDAC
      phosphorylation, prevented MPT, attenuated tubular cell death, and ameliorated
      paraquat-induced AKI. Our data suggest that the redox-sensitive GSK3beta
      regulates renal tubular injury in AKI by controlling the activity of MPT
      regulators. 

PMID- 23973864
TI  - Antimicrobial activity and mechanism of action of a novel cationic alpha-helical
      octadecapeptide derived from heat shock protein 70 of rice.
AB  - Hsp70(241-258), an octadecapeptide derived from the heat shock protein 70 (Hsp70)
      of rice (Oryza sativa L. japonica), is a novel cationic alpha-helical
      antimicrobial peptide (AMP) that contains four lysine, two arginine, and two
      histidine residues. The antimicrobial activity of Hsp70(241-258) against
      Porphyromonas gingivalis, a periodontal pathogen, and Candida albicans, an
      opportunistic fungal pathogen, was quantitatively evaluated using a
      chemiluminescence method that measures ATP derived from viable cells. The 50%
      growth-inhibitory concentrations of Hsp70(241-258) against P. gingivalis and C.
      albicans cells were 63 MUM and 70 MUM, respectively. Hsp70(241-258) had little or
      no hemolytic activity even at 1mM, and showed negligible cytotoxicity up to 300
      MUM. The degrees of calcein leakage from large unilamellar vesicles, which mimic
      the membranes of Gram-negative bacteria, and 3,3'-dipropylthiadicarbocyanine
      iodide release from P. gingivalis cells induced by the addition of Hsp70(241-258)
      increased in a concentration-dependent manner. When Hsp70(241-258) was added to
      calcein-acetoxymethyl ester-loaded C. albicans cells, calcein release from the
      cells increased in a concentration-dependent manner. Flow cytometric analysis
      also showed that the percentages of C. albicans cells stained with propidium
      iodide, a DNA-intercalating dye, increased as the concentration of Hsp70(241-258)
      added was increased. Therefore, Hsp70(241-258) appears to exhibit antimicrobial
      activity against P. gingivalis and C. albicans through membrane disruption. These
      results suggest that Hsp70(241-258) could be useful as a safe and potent AMP
      against P. gingivalis and C. albicans in many fields of health care, especially
      in the control of oral infections.

PMID- 23973865
TI  - Rapid speciation with gene flow following the formation of Mt. Etna.
AB  - Environmental or geological changes can create new niches that drive ecological
      species divergence without the immediate cessation of gene flow. However, few
      such cases have been characterized. On a recently formed volcano, Mt. Etna,
      Senecio aethnensis and S. chrysanthemifolius inhabit contrasting environments of
      high and low altitude, respectively. They have very distinct phenotypes, despite
      hybridizing promiscuously, and thus may represent an important example of
      ecological speciation "in action," possibly as a response to the rapid geological
      changes that Mt. Etna has recently undergone. To elucidate the species'
      evolutionary history, and help establish the species as a study system for
      speciation genomics, we sequenced the transcriptomes of the two Etnean species,
      and the outgroup, S. vernalis, using Illumina sequencing. Despite the species'
      substantial phenotypic divergence, synonymous divergence between the high- and
      low-altitude species was low (dS = 0.016 +/- 0.017 [SD]). A comparison of species
      divergence models with and without gene flow provided unequivocal support in
      favor of the former and demonstrated a recent time of species divergence (153,080
      ya +/- 11,470 [SE]) that coincides with the growth of Mt. Etna to the altitudes
      that separate the species today. Analysis of dN/dS revealed wide variation in
      selective constraint between genes, and evidence that highly expressed genes,
      more "multifunctional" genes, and those with more paralogs were under elevated
      purifying selection. Taken together, these results are consistent with a model of
      ecological speciation, potentially as a response to the emergence of a new, high
      altitude niche as the volcano grew. 

PMID- 23973866
TI  - A novel and enantioselective epoxide hydrolase from Aspergillus brasiliensis CCT
      1435: purification and characterization.
AB  - A novel epoxide hydrolase from Aspergillus brasiliensis CCT1435 (AbEH) was cloned
      and overexpressed in Escherichia coli cells with a 6xHis-tag and purified by
      nickel affinity chromatography. Gel filtration analysis and circular dichroism
      measurements indicated that this novel AbEH is a homodimer in aqueous solution
      and contains the typical secondary structure of an alpha/beta hydrolase fold. The
      activity of AbEH was initially assessed using the fluorogenic probe O-(3,4
      epoxybutyl) umbelliferone and was active in a broad range of pH (6-9) and
      temperature (25-45 degrees C); showing optimum performance at pH 6.0 and 30
      degrees C. The Michaelis constant (KM) and maximum rate (Vmax) values were 495MUM
      and 0.24MUM/s, respectively. Racemic styrene oxide (SO) was used as a substrate
      to assess the AbEH activity and enantioselectivity, and 66% of the SO was
      hydrolyzed after only 5min of reaction, with the remaining (S)-SO ee exceeding
      99% in a typical kinetic resolution behavior. The AbEH-catalyzed hydrolysis of SO
      was also evaluated in a biphasic system of water:isooctane; (R)-diol in 84% ee
      and unreacted (S)-SO in 36% ee were produced, with 43% conversion in 24h,
      indicating a discrete enantioconvergent behavior for AbEH. This novel epoxide
      hydrolase has biotechnological potential for the preparation of enantiopure
      epoxides or vicinal diols. 

PMID- 23973867
TI  - Novel functional Renilla luciferase mutant provides long-term serum stability and
      high luminescence activity.
AB  - Fluorescent and luminescent chemical probes are essential in recent medical
      diagnostics. However, the use of these probes in vivo has raised concerns due to
      their low sensitivity, background signal interference, and non-biocompatibility.
      Therefore, biological chromophores have received much attention as new
      alternatives. In particular, luciferase, a class of oxidative enzyme with
      bioluminescence, has emerged as a promising fluorophore due to its improved
      biocompatibility. However, the enzyme usually possesses weaker luminescence and
      stability relative to its chemically-based competitors. Here, we report a novel
      functional mutant luciferase with both enhanced luminescence and long-term serum
      stability. For the preparation of the modified Renilla luciferase, a new
      bacterial subcloning design was established. The luciferase coding DNA sequence
      was redesigned so that mutant luciferase could be easily expressed in an
      Escherichia coli system. The mutant Renilla luciferase, which we called "m-Rluc,"
      demonstrated characteristic enzymatic functions and showed a 5.6-fold increase in
      luminescence activity. In addition, the enzyme's physiological stability remained
      >80% for more than 5days, in contrast to conventional luciferase, termed "hrluc,"
      which disappeared within a few hours. We suggest that this novel biological
      luciferase probe may be a great tool for both in vitro and in vivo medical
      diagnostics. 

PMID- 23973868
TI  - Prognostic relevance of papillary muscle infarction in reperfused infarction as
      visualized by cardiovascular magnetic resonance.
AB  - BACKGROUND: The prognostic significance of papillary muscle infarction (PapMI) on
      hard clinical outcomes has not been investigated in patients with reperfused ST
      segment-elevation myocardial infarction. Noninvasive investigation by gadolinium
      enhanced cardiac MRI enables the detection of PapMI with high spatial resolution.
      The aim of our study was (1) to assess the incidence, determinants, and clinical
      characteristics of PapMI in a large multicenter cohort of patients with ST
      segment-elevation myocardial infarction and (2) to assess the prognostic
      significance of PapMI at 1-year follow-up. METHODS AND RESULTS: We enrolled 738
      patients with ST-segment-elevation myocardial infarction reperfused by primary
      angioplasty (<12 hours after symptom onset) in this cardiac MRI study at 8
      centers. Cardiac MRI was completed within 1 week after infarction using a
      standardized protocol. Central core laboratory-masked analyses for the presence
      of PapMI were performed. The primary clinical end point of the study was the
      occurrence of major adverse cardiac events. PapMIs were detected in 104 patients
      (14%). The presence of PapMI was associated with larger infarcts (P<0.001), less
      myocardial salvage (P<0.001), impaired left ventricular function (P<0.001), and
      more pronounced reperfusion injury (P=0.02). Patients with PapMI had a
      significantly higher mortality (8 [7.7%] versus 12 [1.9%]) and major adverse
      cardiac events (21 [20.2%] versus 31 [4.9%]) rate at 12-month follow-up (P<0.001,
      respectively). PapMI was identified as a significant independent predictor of
      major adverse cardiac events (hazard ratio, 4.41 [confidence interval, 2.54
      7.68]; P<0.001). CONCLUSIONS: The presence of PapMI is associated with decreased
      myocardial salvage, larger infarcts, and more pronounced reperfusion injury with
      subsequent significantly increased major adverse cardiac event rates.
      Consequently, our data underscore the importance of PapMI as a marker of poor
      outcome in patients with ST-segment-elevation myocardial infarction.

PMID- 23973869
TI  - Multivariate neural network operators with sigmoidal activation functions.
AB  - In this paper, we study pointwise and uniform convergence, as well as order of
      approximation, of a family of linear positive multivariate neural network (NN)
      operators with sigmoidal activation functions. The order of approximation is
      studied for functions belonging to suitable Lipschitz classes and using a moment
      type approach. The special cases of NN operators, activated by logistic,
      hyperbolic tangent, and ramp sigmoidal functions are considered. Multivariate NNs
      approximation finds applications, typically, in neurocomputing processes. Our
      approach to NN operators allows us to extend previous convergence results and, in
      some cases, to improve the order of approximation. The case of multivariate quasi
      interpolation operators constructed with sigmoidal functions is also considered.

PMID- 23973870
TI  - Solving graph data issues using a layered architecture approach with applications
      to web spam detection.
AB  - This paper proposes the combination of two state-of-the-art algorithms for
      processing graph input data, viz., the probabilistic mapping graph self
      organizing map, an unsupervised learning approach, and the graph neural network,
      a supervised learning approach. We organize these two algorithms in a cascade
      architecture containing a probabilistic mapping graph self organizing map, and a
      graph neural network. We show that this combined approach helps us to limit the
      long-term dependency problem that exists when training the graph neural network
      resulting in an overall improvement in performance. This is demonstrated in an
      application to a benchmark problem requiring the detection of spam in a
      relatively large set of web sites. It is found that the proposed method produces
      results which reach the state of the art when compared with some of the best
      results obtained by others using quite different approaches. A particular
      strength of our method is its applicability towards any input domain which can be
      represented as a graph.

PMID- 23973871
TI  - Journal of Biotechnology opens the new section "Genome Announcement".

PMID- 23973872
TI  - Assessment of the Health IT Usability Evaluation Model (Health-ITUEM) for
      evaluating mobile health (mHealth) technology.
AB  - BACKGROUND: Over two decades of research has been conducted using mobile devices
      for health related behaviors yet many of these studies lack rigor. There are few
      evaluation frameworks for assessing the usability of mHealth, which is critical
      as the use of this technology proliferates. As the development of interventions
      using mobile technology increase, future work in this domain necessitates the use
      of a rigorous usability evaluation framework. METHODS: We used two exemplars to
      assess the appropriateness of the Health IT Usability Evaluation Model (Health
      ITUEM) for evaluating the usability of mHealth technology. In the first exemplar,
      we conducted 6 focus group sessions to explore adolescents' use of mobile
      technology for meeting their health Information needs. In the second exemplar, we
      conducted 4 focus group sessions following an Ecological Momentary Assessment
      study in which 60 adolescents were given a smartphone with pre-installed health
      related applications (apps). DATA ANALYSIS: We coded the focus group data using
      the 9 concepts of the Health-ITUEM: Error prevention, Completeness, Memorability,
      Information needs, Flexibility/Customizability, Learnability, Performance speed,
      Competency, Other outcomes. To develop a finer granularity of analysis, the nine
      concepts were broken into positive, negative, and neutral codes. A total of 27
      codes were created. Two raters (R1 and R2) initially coded all text and a third
      rater (R3) reconciled coding discordance between raters R1 and R2. RESULTS: A
      total of 133 codes were applied to Exemplar 1. In Exemplar 2 there were a total
      of 286 codes applied to 195 excerpts. Performance speed, Other outcomes, and
      Information needs were among the most frequently occurring codes. CONCLUSION: Our
      two exemplars demonstrated the appropriateness and usefulness of the Health-ITUEM
      in evaluating mobile health technology. Further assessment of this framework with
      other study populations should consider whether Memorability and Error prevention
      are necessary to include when evaluating mHealth technology.

PMID- 23973873
TI  - Can vitamin E and selenium alleviate the immunologic impact of aluminium on
      pregnant rats' spleens?
AB  - This study aimed to assess if simultaneous administration of vitamin E, selenium
      and aluminium could alleviate the latter's immunologic impact on the spleen.
      Twenty eight virgin albino Sprague Dawley rats were randomly divided into two
      main groups: control (n=12) and experimental (n=18). These groups were divided
      into two subgroups each. The first control group received distiled water and the
      second one vitamin E and selenium for 3months through intragastric tubes. Of the
      two experimental subgroups, the first received oral aluminium chloride (AlCl3) at
      a dose 150mg/kg of body weight/day, and the second received AlCl3 plus vitamin E
      and selenium for 3months. Sixteen (out of eighteen) subject rats became pregnant.
      At day 20 of gestation, dams were sacrificed, and spleens were dissected and
      processed for histologic examination with routine and immunohistologic staining
      and semi-quantitative assessment. Aluminium administration induced a significant
      decrease in the number and density of T-lymphocytes and macrophages in the spleen
      as well as splenic fibrosis during pregnancy. Vitamin E and selenium reduced but
      did not completely prevent these changes. 

PMID- 23973874
TI  - Effects of two different immunotherapies on triple negative breast cancer in
      animal model.
AB  - The ability of immune system to react specifically against tumors inspirited the
      study of triple negative breast cancer (TNBC) immunotherapies. Sixty spontaneous
      breast cancer TA2 mice were randomly divided into three groups: GM-CSF group,
      with therapy of granulocyte-macrophage colony-stimulating factor (GM-CSF)
      combined with breast cancer stem cells associated antigens and cytosine
      phosphorothioate-guanine oligodeoxynucleotides (CpG-ODNs); DC-CIK group, with
      infusions of dendritic cells/cytokine-induced killer (DC/CIK) cells; and PBS
      group as controls. After therapy, the cellular immunity of mice in GM-CSF group
      and DC-CIK group was obviously increased, especially for GM-CSF group (P<0.05),
      tumor regression was obviously observed in GM-CSF group. The survival rate of
      mice in GM-CSF group was significantly higher compared to DC-CIK group and PBS
      group. These results indicated that tumor immunotherapy manifested strong killing
      activity against TNBC. The therapeutic effect of GM-CSF combined with antigens
      and CpG was better than DC-CIK cells. 

PMID- 23973875
TI  - Systematic identification of novel SLE related autoantibodies responsible for
      type I IFN production in human plasmacytoid dendritic cells.
AB  - Plasmacytoid dendritic cells [pDC], also known as type I interferon [IFN]
      producing cells, play a significant role in the pathogenesis of systemic lupus
      erythematosus [SLE]. The current study was undertaken to identify novel SLE
      autoantibody specificities associated with interferon-inducing activity in human
      pDCs. We found that immune complex mixtures from some Interferon signature
      negative [IFN-] and all interferon signature positive [IFN+] SLE patients could
      trigger type I IFN production by pDCs. IgGs from IFN- and IFN+ SLE patients were
      subsequently screened via a high throughput protein microarray to identify novel
      auto-antibody specifities that mediate type I IFN production by pDCs. This
      approach identified five novel autoantibodies that may contribute to type I IFN
      production by pDCs via a nucleic acid dependent mechanism. The newly identified
      autoantibody specificities function in a myriad of cell processess and, to date,
      have not been implicated in SLE pathogenesis. 

PMID- 23973876
TI  - Enhanced anticancer efficacy of snake venom combined with silica nanoparticles in
      a murine model of human multiple myeloma: molecular targets for cell cycle arrest
      and apoptosis induction.
AB  - Multiple myeloma (MM) is a clonal disease of plasma cells that reside in the bone
      marrow (BM). MM is an incurable disease; thus, screening for novel anti-myeloma
      drugs remains critically important. We recently described a silica nanoparticle
      based snake venom delivery model that targets cancer cells, but not normal cells.
      Using this model, we demonstrated a strong enhancement of the antitumor activity
      of snake venom extracted from Walterinnesia aegyptia (WEV) in two breast
      carcinoma cell lines when the venom was combined with silica nanoparticles
      (WEV+NP). In the present study, we aimed to delineate the in vivo therapeutic
      efficacy of WEV+NP in an MM-bearing experimental nude mouse model. We found that
      treatment with WEV+NP or WEV alone significantly inhibited tumor growth compared
      to treatment with NP or vehicle. WEV+NP- and WEV-treated cancer cells exhibited
      marked elevations in oxidative stress and robust reductions in the levels of
      interleukin-6 (IL-6) and B cell-activating factor (BAFF). WEV+NP also decreased
      the surface expression of the chemokine receptors CXCR3, CXCR4 and CXCR6 to a
      greater extent than WEV alone, and WEV+NP subsequently reduced migration in
      response to the cognate ligands CXCL10, CXCL12 and CXCL16. Furthermore, we found
      that WEV+NP strongly inhibited insulin-like growth factor 1 (EGF-1)- and IL-6
      mediated MM cell proliferation, altered the cell cycle and enhanced the induction
      of apoptosis of MM cells. In addition, the results of treatment with WEV+NP or
      WEV alone revealed that the combination of WEV with NP robustly decreased the
      expression of cyclin D1, Bcl-2 and the phosphorylation of AKT; increased the
      expression of cyclin B1; altered the mitochondrial membrane potential; increased
      the activity of caspase-3, -8 and -9; and sensitized MM cells to growth arrest
      and apoptosis. Our data reveal the therapeutic potential of the nanoparticle
      sustained delivery of snake venom to fight cancer cells. 

PMID- 23973877
TI  - Cytotoxic activity of ex-vivo generated IFNalpha-induced monocyte-derived
      dendritic cells in brain glioma patients.
AB  - Recent studies have revealed that besides the important role in triggering the
      adoptive antitumor immunity, dendritic cells (DCs) possess direct cytotoxic
      antitumor activity. Here, we investigated brain glioma patient monocyte-derived
      DCs generated in the presence of IFNalpha and GM-CSF (IFN-DCs). These DCs were
      characterized by reduced cytotoxic activity against TRAIL-resistant HEp-2 cells.
      The impairment of DC cytotoxic function was observed mainly in high-grade glioma
      patients and associated with poor survival. The dysfunction of patient DC
      cytotoxicity was partially restored under in vitro pretreatment of DCs with
      double-stranded human DNA as well as rIL-2. In contrast to healthy donors, IFN
      DCs in a part of high-grade glioma patients also failed to lyse primary
      autologous or allogeneic glioma cells. Our findings point to possible
      contribution of DC impairment in tumor pathogenesis in brain glioma and justify
      the necessity to evaluate and correct DC cytotoxic function when exploring DCs as
      cancer vaccines in glioma. 

PMID- 23973878
TI  - 4-Hydroxy-2-nonenal modified histone-H2A: a possible antigenic stimulus for
      systemic lupus erythematosus autoantibodies.
AB  - Protein modifications by 4-hydroxy-2-nonenals (HNE) are involved in various
      diseases. Histones are DNA protective nucleoprotein, which adopt different
      structures under oxidative stress. This study was undertaken to test the role of
      HNE-modified-histone-H2A (HNE-H2A) in systemic lupus erythematosus (SLE). Our
      data revealed that HNE-mediated-lipid peroxidation in histone-H2A caused
      alteration in histidine, lysine and cystein residues. In addition, protein
      carbonyl contents were also high in HNE-H2A. HNE-specific quencher, L-carnosine
      further reiterates HNE-modifications. Specificity of autoantibodies from SLE
      patients (n=48) were analyzed towards HNE-H2A and their results were compared
      with sex- and age-matched controls (n=36). SLE autoantibodies show preferential
      binding to HNE-H2A in comparison with histone-H2A (p<0.0001). Furthermore, HNE
      H2A was also detected in SLE peripheral blood mononuclear cells. In conclusion,
      this is the first study to demonstrate the role of HNE-modified-histone in SLE.
      Preferential binding of HNE-H2A by affinity purified SLE-IgG pointed out the
      likely role of HNE-H2A in the initiation/progression of SLE. 

PMID- 23973879
TI  - Molecular phylogeny of the Notostraca.
AB  - We used a combined analysis of one nuclear (28S rDNA) and three mitochondrial
      markers (COI, 12S rDNA, 16S rDNA) to infer the molecular phylogeny of the
      Notostraca, represented by samples from the six continents that are inhabited by
      this group of branchiopod crustaceans. Our results confirm the monophyly of both
      extant notostracan genera Triops and Lepidurus with good support in model based
      and maximum parsimony analyses. We used branchiopod fossils as a calibration to
      infer divergence times among notostracan lineages and accounted for rate
      heterogeneity among lineages by applying relaxed-clock models. Our divergence
      date estimates indicate an initial diversification into the genera Triops and
      Lepidurus in the Mesozoic, most likely at a minimum age of 152.3-233.5 Ma, i.e.,
      in the Triassic or Jurassic. Implications for the interpretation of fossils and
      the evolution of notostracan morphology are discussed. We further use the
      divergence date estimates to formulate a biogeographic hypothesis that explains
      distributions of extant lineages predominantly by overland dispersal routes. We
      identified an additional hitherto unrecognised highly diverged lineage within
      Lepidurus apus lubbocki and three additional previously unknown major lineages
      within Triops. Within T. granarius we found deep differentiation, with
      representatives distributed among three major phylogenetic lineages. One of these
      major lineages comprises T. cancriformis, the T. mauritanicus species group and
      two hitherto unrecognised T. granarius lineages. Samples that were
      morphologically identified as T. granarius diverged from the most basal nodes
      within this major lineage, and divergence dates suggested an approximate age of
      23.7-49.6 Ma for T. cancriformis, indicating the need for a taxonomic revision of
      Triassic and Permian fossils that are currently attributed to the extant T.
      cancriformis. We thus elevate T. cancriformis minor to full species status as
      Triops minorTrusheim, 1938 and include in this species the additional Upper
      Triassic samples that were attributed to T. cancriformis. We further elevate T.
      cancriformis permiensis to full species status as Triops permiensisGand et al.,
      1997.

PMID- 23973880
TI  - Scapular dyskinesis: practical applications.

PMID- 23973881
TI  - Republished research: effect of specific exercise strategy on need for surgery in
      patients with subacromial impingement syndrome: randomised controlled study.

PMID- 23973883
TI  - Familial differences in the effects of mercury on reproduction in zebra finches.
AB  - Ecotoxicologists often implicitly assume that populations are homogenous entities
      in which all individuals have similar responses to a contaminant. However,
      genetically variable responses occur within populations. This variation can be
      visualized using dose-response curves of genetically related groups, similar to
      the way that evolutionary biologists construct reaction norms. We assessed the
      variation in reproductive success of full-sibling families of captive zebra
      finches (Taeniopygia guttata) experimentally exposed to methylmercury. We found
      significant variation among families in the effects of methylmercury on several
      reproductive parameters. This variation suggests that there may be strong
      responses to selection for resistant genotypes in contaminated areas. This has
      important implications for the evolution of tolerance as well as risk assessment
      and wildlife conservation efforts on sites with legacy contamination. 

PMID- 23973884
TI  - Source contribution analysis of surface particulate polycyclic aromatic
      hydrocarbon concentrations in northeastern Asia by source-receptor relationships.
AB  - We analyzed the source-receptor relationships for particulate polycyclic aromatic
      hydrocarbon (PAH) concentrations in northeastern Asia using an aerosol chemical
      transport model. The model successfully simulated the observed concentrations. In
      Beijing (China) benzo[a]pyren (BaP) concentrations are due to emissions from its
      own domain. In Noto, Oki and Tsushima (Japan), transboundary transport from
      northern China (>40  degrees N, 40-60%) and central China (30-40  degrees N, 10
      40%) largely influences BaP concentrations from winter to spring, whereas the
      relative contribution from central China is dominant (90%) in Hedo. In the
      summer, the contribution from Japanese domestic sources increases (40-80%) at the
      4 sites. Contributions from Japan and Russia are additional source of BaP over
      the northwestern Pacific Ocean in summer. The contribution rates for the
      concentrations from each domain are different among PAH species depending on
      their particulate phase oxidation rates. Reaction with O3 on particulate surfaces
      may be an important component of the PAH oxidation processes.

PMID- 23973885
TI  - Accumulation of wet-deposited radiocaesium and radiostrontium by spring oilseed
      rape (Brassica napus L.) and spring wheat (Triticum aestivum L.).
AB  - The accumulation of (134)Cs and (85)Sr within different parts of spring oilseed
      rape and spring wheat plants was investigated, with a particular focus on
      transfer to seeds after artificial wet deposition at different growth stages
      during a two-year field trial. In general, the accumulation of radionuclides in
      plant parts increased when deposition was closer to harvest. The seed of spring
      oilseed rape had lower concentrations of (85)Sr than spring wheat grain. The
      plants accumulated more (134)Cs than (85)Sr. We conclude that radionuclides can
      be transferred into human food chain at all growing stages, especially at the
      later stages. The variation in transfer factors during the investigation, and in
      comparison to previous results, implies the estimation of the risk for possible
      transfer of radionuclides to seeds in the event of future fallout during a
      growing season is still subject to considerable uncertainty. 

PMID- 23973886
TI  - Crystal structure of 2A proteinase from hand, foot and mouth disease virus.
AB  - EV71 is responsible for several epidemics worldwide; however, the effective
      antiviral drug is unavailable to date. The 2A proteinase (2A(pro)) of EV71
      presents a promising drug target due to its multiple roles in virus replication,
      inhibition of host protein synthesis and evasion of innate immunity. We
      determined the crystal structure of EV71 2A(pro) at 1.85A resolution, revealing
      that the proteinase maintains a chymotrypsin-like fold. The active site is
      composed of the catalytic triads C110A, H21 and D39 with the geometry similar to
      that in other picornaviral 2A(pro), 3C(pro) and serine proteinases. The cI-to-eI2
      loop at the N-terminal domain of EV71 2A(pro) adopts a highly stable conformation
      and contributes to the hydrophilic surface property, which are strikingly
      different in HRV2 2A(pro) but are similar in CVB4 2A(pro). We identified a
      hydrophobic motif "LLWL" followed by an acidic motif "DEE" at the C-terminus of
      EV71 2A(pro). The "LLWL" motif is folded into the beta-turn structure that is
      essential for the positioning of the acidic motif. Our structural and mutagenesis
      study demonstrated that both the negative charging and the correct positioning of
      the C-terminus are essential for EV71 replication. Deletion of the "LLWL" motif
      abrogated the proteolytic activity, indicating that the motif is critical for
      maintaining the active proteinase conformation. Our findings provide the
      structural and functional insights into EV71 2A(pro) and establish a framework
      for structure-based inhibitor design. 

PMID- 23973887
TI  - Liquid and solid self-microemulsifying drug delivery systems for improving the
      oral bioavailability of andrographolide from a crude extract of Andrographis
      paniculata.
AB  - The purpose of this study was to develop self-microemulsifying formulations of an
      Andrographis paniculata extract in liquid and pellet forms for an improved oral
      delivery of andrographolide. The optimized liquid self-microemulsifying drug
      delivery system (SMEDDS) was composed of A. paniculata extract (11.1%), Capryol
      90 (40%), Cremophor RH 40 (40%) and Labrasol (8.9%). This liquid SMEDDS was
      further adsorbed onto colloidal silicon dioxide and microcrystalline cellulose,
      and converted to SMEDDS pellets by the extrusion/spheronization technique. The
      microemulsion droplet sizes of the liquid and pellet formulations after dilution
      with water were in the range of 23.4 and 30.3 nm. The in vitro release of
      andrographolide from the liquid SMEDDS and SMEDDS pellets was 97.64% (SD 1.97%)
      and 97.74% (SD 3.36%) within 15 min, respectively while the release from the
      initial extract was only 10%. The oral absorption of andrographolide was
      determined in rabbits. The C(max) value of andrographolide from the A. paniculata
      extract liquid SMEDDS and SMEDDS pellet formulations (equivalent to 17.5mg/kg of
      andrographolide) was 6-fold and 5-fold greater than the value from the initial
      extract in aqueous suspension (equivalent to 35 mg/kg of andrographolide),
      respectively. In addition, the AUC(0-12h) was increased 15-fold by the liquid
      SMEDDS and 13-fold by the SMEDDS pellets compared to the extract in aqueous
      suspension, respectively. The results clearly indicated that the liquid and solid
      SMEDDS could be effectively used to improve the dissolution and oral
      bioavailability that would also enable a reduction in the dose of the poorly
      water soluble A. paniculata extract.

PMID- 23973888
TI  - A polyphosphoester conjugate of melphalan as antitumoral agent.
AB  - The low molecular weight of many chemotherapeutics causes their untargeted
      distribution in the body and fast renal clearance, which leads to a loss of
      therapeutic activity and to unspecific toxic side effects. Therefore, there is a
      growing interest in conjugating anticancer drugs to water soluble polymers and
      thus, take advantage of the 'enhanced permeability and retention' (EPR) effect in
      tumors. In this study, water soluble polyphosphoesters were used as polymer
      carriers of melphalan hydrochloride (hydrochloride of p-bis(2-chloroethyl)amino-L
      phenylalanine), which is a multifunctional alkylating agent. Melphalan was
      chemically immobilized by covalent bonding to poly(oxyethylene H-phosphonate)
      under Atherton-Todd reaction conditions. Novel polymer-melphalan complexes with
      ionic and hydrogen bonds were designed as controls, basing on two other
      biodegradable polyphosphoesters: poly(hydroxyoxyethylene phosphate) and
      poly(methyloxyethylene phosphate). The structure of the formed products was
      elucidated by (1)H, (13)C, (31)P NMR and FT-IR spectroscopy. The cytotoxic effect
      of the melphalan formulations was evaluated on different tumor cell lines. The
      novel polymer formulations showed a concentration dependent antitumoral activity,
      comparable to the effect of unmodified melphalan. The polymer-melphalan conjugate
      was also evaluated in vivo in the human hepatocellular carcinoma HuH7 xenograft
      mouse model. It improved the therapeutic efficacy of pure melphalan without
      causing side effects.

PMID- 23973889
TI  - Human amniotic epithelial cell niche enhances the functional properties of human
      corneal endothelial cells via inhibiting P53-survivin-mitochondria axis.
AB  - The particular microenvironment or niche plays an important role in determining
      the fate of stem cells and adult cells. The objective of this study was to
      explore the potential role of the niche of human amniotic epithelial cells in
      enhancing the functional properties of human corneal endothelial cells (HCECs).
      The HCECs were cultured in different media, including corneal endothelium medium
      (CEM), 20% human amniotic epithelial cell culture medium (20% HAEC-Me), and 20%
      human amniotic epithelial cell-conditioned medium (20% HAEC-CM). We observed that
      the HCECs cultured in the 20% HAEC-CM had an increased proliferative capacity,
      higher colony-forming efficiency (CFE), fewer apoptotic cells, and similar cell
      junction formation capabilities and pump functionality compared with primary
      HCECs. Compared with CEM and 20% HAEC-Me, the 20% HAEC-CM system enhanced the
      functional properties of HCECs by reducing the generation of reactive oxygen
      species (ROS), maintaining the membrane potential (Deltapsim) at higher levels,
      reducing the expression of the p53 protein, and increasing the level of survivin
      protein expression. This study may shed light on the expansion of HCECs and the
      clinical applications of these cells in regenerative medicine, especially in
      corneal tissue engineering. 

PMID- 23973890
TI  - Four tumor necrosis factor alpha genes polymorphisms and periodontitis risk in a
      Chinese population.
AB  - BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) has been implicated in the
      pathogenesis of generalized aggressive periodontitis (AgP) and chronic
      periodontitis (CP). The objective of the present study was to evaluate the
      association of four TNF-alpha gene polymorphisms (-1031T/C, -857C/T, -308G/A and 
      238G/A) with susceptibility to AgP and CP in a Chinese population. METHODS: A
      hospital-based case-control study was conducted in in patients with CP (n = 180),
      AgP (n = 180) and healthy controls (n = 180). Gene promoter polymorphisms were
      analyzed by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) assay. Genotype and allele frequencies were analyzed using the chi
      square test and logistic regression analysis. RESULTS: TNF-alpha -1031CC genotype
      was significantly higher [odds ratio (OR) = 2.36, 95% confidence interval (CI) =
      1.03, 5.43; P = 0.04] in patients with CP compared with healthy controls. TNF
      alpha -308AA genotype was significantly higher (OR = 2.71, 95% CI = 1.09, 6.73; P
      = 0.03) in patients with AgP compared with healthy controls. No association was
      found of TNF-alpha -857C/T and -238G/A polymorphisms with susceptibility to AgP
      or CP. CONCLUSIONS: Our data demonstrated that TNF-alpha -1031CC genotype was a
      risk factor for CP, and that TNF-alpha -308AA genotype was a risk factor for AgP.
      But there is a lack of association of TNF-alpha -857C/T and -238G/A polymorphisms
      with susceptibility to AgP or CP in a Chinese population.

PMID- 23973891
TI  - Variants in interleukin family of cytokines genes influence clearance of high
      risk HPV in HIV-1 coinfected African-American adolescents.
AB  - Our work aimed to examine the potential influence of variants in
      interleukin/interleukin receptors genes on high-risk (HR-HPV) HPV clearance.
      Clearance of genital HR-HPV infection was evaluated for 134 HIV-1 seropositive
      African-American female adolescents from the Reaching for Excellence in
      Adolescent Care and Health (REACH) cohort. Genotyping targeted 225 single
      nucleotide polymorphisms (SNPs) within the exons, 5' untranslated region (UTR)
      and 3' UTR sequences of 27 immune-related candidate genes encoding interleukin
      family of cytokines. Cox proportional hazard models were used to determine the
      association of type-specific HPV clearance adjusting for time-varying CD4+ T-cell
      count and low-risk (LR-HPV) HPV co-infections. HR-HPV clearance rates were
      significantly (p < 0.001) associated with five SNPs (rs228942, rs419598,
      rs315950, rs7737000, and rs9292618) mapped to coding and regulatory regions in
      three genes (IL2RB, IL1RN, and IL7R). These data suggest that the analyzed
      genetic variants in interleukin family of cytokines modulate HR-HPV clearance in
      HIV-1 seropositive African-Americans that warrants replication.

PMID- 23973892
TI  - X-linked inhibitor of apoptosis (XIAP) deficiency: the spectrum of presenting
      manifestations beyond hemophagocytic lymphohistiocytosis.
AB  - X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in BIRC4
      was initially described in patients with X-linked lymphoproliferative syndrome
      (XLP) who had no mutations in SH2D1A. In the initial reports, EBV-associated
      hemophagocytic lymphohistiocytosis (HLH) was the predominant clinical phenotype.
      Among 25 symptomatic patients diagnosed with XIAP deficiency, we identified 17
      patients who initially presented with manifestations other than HLH. These
      included Crohn-like bowel disease (n=6), severe infectious mononucleosis (n=4),
      isolated splenomegaly (n=3), uveitis (n=1), periodic fever (n=1), fistulating
      skin abscesses (n=1) and severe Giardia enteritis (n=1). Subsequent
      manifestations included celiac-like disease, antibody deficiency, splenomegaly
      and partial HLH. Screening by flow cytometry identified 14 of 17 patients in our
      cohort. However, neither genotype nor protein expression nor results from cell
      death studies were clearly associated with the clinical phenotype. Only mutation
      analysis can reliably identify affected patients. XIAP deficiency must be
      considered in a wide range of clinical presentations. 

PMID- 23973893
TI  - Sulcozoa revealed as a paraphyletic group in mitochondrial phylogenomics.
AB  - Recently, phylogenomic analyses have been used to assign the vast majority of
      eukaryotes into only a handful of supergroups. However, a few enigmatic lineages
      still do not fit into this simple picture. Such lineages may have originated
      early in the history of eukaryotes and are therefore of key importance in
      deduction of cellular evolution. In this study, we focus on two deeply diverging
      lineages, Diphyllatea and Thecamonadea. They are classified in the same phylum,
      Sulcozoa, but previous multigene phylogenetic analyses have included only one of
      these two lineages. It is therefore unclear whether they constitute one group or
      two distinct lineages. The study of rare genomic changes reveals that both have
      the fused dihydrofolate reductase (DHFR) and thymidylate synthase (TS) genes
      (i.e. DHFR-TS), which are separated in all other unikonts that have been
      investigated, indicating a possible close relationship. Their phylogenetic
      positions have implications for the classification of Sulcozoa and the early
      eukaryote evolution. Here we present a phylogenomic analysis of these species
      that include Illumina and 454 transcriptome data from two Collodictyon strains. A
      total of 42 mitochondrial proteins, which correspond to orthologs published from
      Thecamonas trahens (Thecamonadea), were used to reconstruct their phylogenies. In
      the resulting trees, Collodictyon appears as sister to Amoebozoa, whereas
      Thecamonas branches as the closest relative of Opisthokonta (i.e. the animal,
      fungi and unicellular Choanozoa). In contrast, the position of another early
      diverging eukaryote, Malawimonas, is unresolved. The separation of Collodictyon
      and Thecamonas in our studies suggests that the recently proposed Sulcozoa group
      is most likely paraphyletic. Furthermore, the data support the hypothesis that
      the two supergroups Opisthokonta and Amoebozoa, which comprise a great diversity
      of eukaryotes, have originated from a sulcozoan ancestor. 

PMID- 23973894
TI  - Historical biogeography of Eastern Asian-Eastern North American disjunct
      Melaphidina aphids (Hemiptera: Aphididae: Eriosomatinae) on Rhus hosts
      (Anacardiaceae).
AB  - Intercontinental biotic disjunctions have been documented and analyzed in
      numerous Holarctic taxa. Patterns previously synthesized for animals compared to
      plants suggest that the timing of animal disjunctions are mostly Early Tertiary
      and were generated by migration and vicariance events occurring in the North
      Atlantic, while plant disjunctions are mostly Mid-Late Tertiary and imply
      migration and vicariance over Beringia. Melaphidina aphids (Hemiptera: Aphididae:
      Fordini) exhibit host-alternating life cycles comprising an obligate seasonal
      shift between Rhus subgenus Rhus species (Anacardiaceae) and mosses (Bryophyta).
      Similar to their Rhus hosts, melaphidines are distributed disjunctly between
      Eastern Asia and Eastern North America. We examined evolutionary relationships
      within Melaphidina to determine the position of the North American lineage, date
      its divergence from Asian relatives, and compare these results to a previous
      historical biogeographic study of Rhus. We sampled nine species and three
      subspecies representing all six genera of Melaphidina. Data included sequences of
      mitochondrial cytochrome c oxidase subunits I and II+leucine tRNA, cytochrome b,
      and nuclear elongation factor 1alpha genes. Phylogenetic analyses (Bayesian,
      maximum-likelihood, parsimony) of the combined data (3282 bp) supported the
      monophyly of all genera except Nurudea and Schlechtendalia, due to the position
      of N. ibofushi. While the exact position of the North American Melaphis was not
      well resolved, there was high support for a derived position within Asian taxa.
      The divergence of Melaphis from Asian relatives centered on the Eocene-Oligocene
      boundary (~33-35Ma), which coincides with closure of Beringian Land Bridge I.
      This also corresponded to the Asian-North American disjunction previously
      estimated for subgenus Rhus spp. We suggest the late-Eocene Bering Land Bridge as
      the most likely migration route for Melaphis ancestors, as was also hypothesized
      for North American Rhus ancestors. Results for the Melaphidina disjunction depart
      from the modal pattern in animal lineages, and present a case where insect and
      host-plant taxa apparently responded similarly to Tertiary climate change.

PMID- 23973895
TI  - Total invasion of the pancreatic gland by a rare aggressive IPMN: Report of a
      case.
AB  - INTRODUCTION: The intraductal papillary mucinous neoplasms (IPMNs) are
      increasingly diagnosed entities with high potential of malignancy and significant
      recurrence rates. PRESENTATION OF CASE: In this case report a rare mixed IPMN
      with full invasion of the pancreatic ducts was identified. DISCUSSION:
      Difficulties in determining the grade of pancreatic duct involvement make the
      surgical management tough. CONCLUSION: In multifocal IPMNs the management of the
      patients is even more challenging. In this case the patient was treated
      successfully with total pancreatectomy.

PMID- 23973896
TI  - A novel approach for removing an intra-renal migrated MemokathTM stent.
AB  - INTRODUCTION: The use of metallic stents in managing benign and malignant
      ureteric strictures is gaining increasing popularity in urology and has been
      shown to be a safe and effective alternative to the commonly used double J
      stents. PRESENTATION OF CASE: We present here the case of a 54 year old female
      with a symptomatic benign ureteric narrowing at the pelvi-ureteric junction of
      her left kidney who was successfully managed with a metallic MemokathTM stent
      inserted at the site of the stricture. She went on to develop a rare complication
      of proximal migration of the stent into the kidney necessitating removal.
      DISCUSSION: Our study systematically reviews the published evidence for the
      clinical effectiveness of metallic ureteric stents in stricture management and
      details a novel and safe approach that was successfully used to remove the intra
      renal migrated stent in an antegrade percutaneous fashion. CONCLUSION: Our report
      highlights a rare complication of metallic ureteric stents and a novel approach
      to their removal. This has significant importance for the urologist managing an
      awkwardly positioned stent lying within the kidney and hence difficult to
      manipulate via the previously published retrograde approaches.

PMID- 23973897
TI  - Lumbar hernia after breast reconstruction.
AB  - INTRODUCTION: Lumbar hernia is a rare complication that can occur after breast
      reconstruction using a latissimus dorsi flap. The defect occurs within the
      superior lumbar triangle and may result in visceral incarceration. PRESENTATION
      OF CASE: We report a 61-year-old female who presented with a left sided lumbar
      bulge and pain 7 years following a modified radical mastectomy and latissimus
      dorsi flap reconstruction. Computed tomography demonstrated a lumbar hernia with
      incarcerated colon. The patient underwent a successful laparoscopic repair with
      prosthetic mesh underlay. DISCUSSION: Lumbar hernias may be congenital, secondary
      to trauma or prior surgery. Imaging studies assist in excluding soft tissue
      tumors, infections, hematoma or abdominal wall denervation atrophy, which may
      also present as a lumbar bulge. Repair may be performed in an open, laparoscopic
      or retroperitoneoscopic approach. CONCLUSION: Laparoscopic lumbar hernia repair
      with mesh is a safe and feasible way to manage an uncommon complication after
      breast reconstruction with a latissimus flap.

PMID- 23973898
TI  - Laparoscopic sleeve gastrectomy in management of weight regain after failed
      laparoscopic plication.
AB  - INTRODUCTION: Weight regain after bariatric surgery remains a challenging problem
      with regard to its surgical management. PRESENTATION OF CASE: A 30 year-old
      female patient with weight regain after failed laparoscopic gastric plication and
      previous gastric banding was evaluated in a tertiary-care university setting. Her
      last body mass index was calculated as 40.4kg/m(2). Preoperative ultrasonography
      revealed cholelithiasis. Laparoscopic sleeve gastrectomy with cholecystectomy was
      planned as a redo surgery. A floopy and plicated stomach with increased wall
      thickness of the greater curvature was seen. After adhesiolysis between the
      plicated part of stomach and the surrounding omental tissues, concomitant
      laparoscopic sleeve gastrectomy and cholecystectomy were performed. She was
      discharged on the 4th post-operative day without any complaint. At the
      postoperative 3rd month, her body mass index was recorded as 24kg/m(2).
      DISCUSSION: Redo surgery of morbid obesity after failed bariatric surgery is a
      technically demanding issue. Type of the surgical treatment should be decided by
      the attending surgeon based on the morphology of the remnant stomach caused by
      previous operations. CONCLUSION: As a redo surgery after failed laparoscopic
      gastric plication and gastric banding procedures, laparoscopic sleeve gastrectomy
      may be regarded as a safe and feasible approach in experienced hands.

PMID- 23973899
TI  - Desmoplastic fibroma of the ilium.
AB  - INTRODUCTION: The desmoplastic fibroma is a rare locally invasive bone tumour.
      Surgical resection with minimal margins is recommended. PRESENTATION OF CASE: A
      15 year-old boy was referred with chronic left thigh pain. MRI revealed a bone
      lesion within the cavity of the inner table of the left iliac wing without
      invasion of the underlying bone marrow. A surgical biopsy revealed a desmoplastic
      bone fibroma. A partial resection of the inner table of the iliac wing sparing
      the outer table was performed. At the latest follow-up the initially spared iliac
      wing had needed further resection. The reason proposed for this is
      devascularisation by substantial periosteal stripping causing partial resorption
      initially, then necrosis and ultimately ulceration through the skin necessitating
      further surgical resection. DISCUSSION: The technique of resection of a pelvic
      desmoplastic fibroma sparing the outer table of the iliac wing has not previously
      been reported. The objective of a limited resection was to minimize the risk of a
      postsurgical limp caused by weakness of the gluteus medius muscle. However we
      report that this technique did not work in this case. A wider resection of the
      iliac wing as it is recommended for a malignant tumour would have yielded a
      similar final outcome. CONCLUSION: A partial resection of the iliac wing seemed
      an appealing technique for a benign tumour of the inner table of the iliac wing.
      However, considering the complications encountered, the authors advise a simple
      "en bloc" resection of the iliac wing for this type of tumour in this location.

PMID- 23973900
TI  - Hernia of cecum and ascending colon through the foramen of Winslow.
AB  - INTRODUCTION: Internal hernias through the foramen of Winslow are rare events and
      constitute 8% of internal hernias but only 0.1% of all abdominal hernias.
      PRESENTATION OF CASE: A 62-year-old man presented with upper abdominal pain,
      distention and vomiting, and was shown on CT scan to have the right colon and
      cecum herniating into the lesser sac through the foramen of Winslow. This
      diagnosis was confirmed at laparotomy as well as a midgut volvulus and right
      hemicolectomy was performed because of ischemic changes of the cecum. DISCUSSION:
      Six developmental abnormalities may result in internal herniation of bowel
      contents in the abdomen: (i) abnormal retroperitoneal fixation of the mesentery
      resulting in anomalous positioning of the intestine; (ii) incomplete mesenteric
      surfaces with the presence of abnormal opening through which the intestine
      herniates, (iii) abnormally large internal foramina or fossae (e.g. foramen of
      Winslow); (iv) abnormally long small-bowel mesentery; (v) an elongated right
      hepatic lobe thought to guide bowel into the foramen of Winslow, and (vi)
      persistence of the ascending mesocolon allowing marked mobility of the right
      colon. CONCLUSION: We believe that hypermobile cecum was responsible for the
      internal herniation through the foramen of Winslow and that this served as the
      lead point allowing for the midgut volvulus. There is no consensus on the
      surgical management of internal hernias through the Foramen of Winslow when the
      herniated contents are grossly viable. The literature in this regard is scarce
      and surgical decision making is based on surgeon preference and the viability of
      the herniated intraabdominal contents.

PMID- 23973901
TI  - Laparoscopic treatment of celiac axis compression syndrome (CACS) and hiatal
      hernia: Case report with bleeding complications and review.
AB  - INTRODUCTION: Median arcuate ligament (MAL) malposition is a rare cause of celiac
      axis compression syndrome (CACS) or Dunbar syndrome. PRESENTATION OF CASE: A 26
      year-old female presented with severe postprandial epigastric pain, weight loss,
      heartburn and regurgitation unresponsive to medical therapy. CT angiography and
      duplex ultrasound demonstrated the MAL crossing anterior to the celiac artery
      (CA). Reconstructions demonstrated CA compression, while the superior mesenteric
      artery (SMA) was normal. The MAL was laparoscopically divided, releasing the
      celiac axis. A concomitant Nissen fundoplication was performed. At 3-months
      follow-up, the CT-scan demonstrated no evidence of CACS with complete symptom
      resolution. DISCUSSION: Dunbar's syndrome can be treated with endovascular
      surgery, laparoscopic MAL division or vascular surgery.Six anatomical and
      morphologic variations of aortic and esophageal hiatus are described. The result
      of the analysis of these anatomical data leads to the conclusion that hiatus
      hernia, Dunbar's syndrome and GERD have a common etiopathogenesis and
      physiopathology. CONCLUSION: Laparoscopic treatment is useful and feasible in
      centers with experience in majorlaparoscopic surgery with reduced invasiveness,
      better cosmetic effect and shorter postoperative course.

PMID- 23973902
TI  - Mucinous cystadenoma of the appendix presenting with an elevated carcinoembryonic
      antigen (CEA): Report of two cases and review of the literature.
AB  - INTRODUCTION: Despite the fact the mucocoele of the appendix is a rare entity it
      has been the subject of much interest in the literature. The term mucocoele
      refers to cystic dilatation of the appendix filled with mucin resulting from
      proximal obstruction of the appendix lumen. PRESENTATION OF CASE: We report two
      patients presenting with mucinous cystadenoma of the appendix with elevation of
      serum carcinoembryonic antigen (CEA), which has rarely been reported. Both
      patients had mild symptoms and a normal colonoscopy preoperatively. The diagnosis
      was not suspected in one patient prior to surgery. The elevated CEA prompted
      additional diagnostic radiologic investigations including ultrasonography, and
      computed tomography scans. The patients had uneventful appendicectomies with
      subsequent normalization of their CEA levels. DISCUSSION: Mucinous cystadenoma of
      the appendix is a rare pathological entity characterized by a dilated mucous
      filled appendix. The presence of an elevated CEA associated with the presence of
      this entity is a rare presentation. CONCLUSION: Because the diagnosis is rarely
      suspected prior to surgery patients with an enlarged appendix with associated
      elevated CEA levels should have careful investigations to exclude malignancy.

PMID- 23973903
TI  - Obturator hernia: A case report and review of the literature.
AB  - INTRODUCTION: An obturator hernia is a rare condition but is associated with the
      highest mortality of all abdominal wall hernias. Early surgical intervention is
      often hindered by clinical and radiological diagnostic difficulty. The following
      case report highlights these diagnostic difficulties, and reviews the current
      literature on management of such cases. PRESENTATION OF CASE: We present the case
      of an 86-year-old lady who presented with intermittent small bowel obstruction,
      clear hernial orifices, and right medial thigh pain. Pre-operative CT imaging was
      suggestive of an obstructed right femoral hernia. However, intra-operatively the
      femoral canal was clear and an obstructed hernia was found passing through the
      obturator foramen lying between the pectineus and obturator muscles in the
      obturator canal. DISCUSSION: Obturator hernias are notorious for diagnostic
      difficulty. Patients often present with intermittent bowel obstruction symptoms
      due to a high proportion exhibiting Richter's herniation of the bowel. Hernial
      sacs can irritate the obturator nerve within the canal, manifesting as medial
      thigh pain, and often no hernial masses can be detected on clinical examination.
      Increasing speed of diagnosis through early CT imaging has been shown to reduce
      the morbidity and mortality associated with obturator hernias. However, over
      reliance on CT findings should be cautioned, as imaging and operative findings
      may not always correlate. CONCLUSION: A high suspicion for obturator hernia
      should be maintained when assessing a patient presenting with bowel obstruction
      particularly where intermittent symptoms or medial thigh pain are present. Rapid
      clinical and appropriate radiological assessment, followed by early surgery is
      critical to successful treatment.

PMID- 23973904
TI  - Syntactic priming in Chinese sentence comprehension: evidence from event-related
      potentials.
AB  - Using the event-related potential (ERP) technique, this study examined the nature
      of syntactic priming effects in Chinese. Participants were required to read prime
      target sentence pairs each embedding an ambiguous relative clause (RC) containing
      either the same verb or a synonymous verb. In Chinese, the word de serves as a
      relative clause marker. During reading a potential Chinese RC structure (either
      the prime or the target sentence), Chinese readers initially expect to read an
      subject-verb-object (SVO) structure but the encounter of a relative clause marker
      de would make readers abandon the initial strategy and reanalyze the structure as
      a relative clause. A reduced P600 effect was elicited by the critical word de in
      the target sentence containing the same initial verb as in the prime sentence. No
      significant reduction of the P600 was observed in the target sentences in the
      synonymous condition. The results demonstrated that verb repetition but not
      similarity in meaning produced a syntactic priming effect in Chinese. The
      constraint-based lexicalist hypothesis and the argument structure theory were
      adopted to explain the syntactic priming effect obtained in the current study.

PMID- 23973906
TI  - A novel promising biomolecule immobilization matrix: synthesis of functional
      benzimidazole containing conducting polymer and its biosensor applications.
AB  - In order to construct a robust covalent binding between biomolecule and
      immobilization platform in biosensor preparation, a novel functional monomer 4
      (4,7-di(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)benzaldehyde (BIBA) was designed
      and successfully synthesized. After electropolymerization of this monomer,
      electrochemical and spectroelectrochemical properties were investigated in
      detail. To fabricate the desired biosensor, glucose oxidase (GOx) was immobilized
      as a model enzyme on the polymer coated graphite electrode with the help of
      glutaraldehyde (GA). During the immobilization step, an imine bond was formed
      between the free amino groups of enzyme and aldehyde group of polymer. The
      surface characterization and morphology were investigated to confirm
      bioconjugation by X-ray photoelectron spectroscopy (XPS) and transmission
      electron microscopy (TEM) at each step of biosensor fabrication. The optimized
      biosensor shows good linearity between 0.02mM and 1.20mM and a low limit of
      detection (LOD) of 2.29MUM. Kinetic parameters Km(app) and Imax were determined
      as 0.94mM and 10.91MUA, respectively. The biosensor was tested for human blood
      serum samples. 

PMID- 23973905
TI  - Learning from the spinal cord: how the study of spinal cord plasticity informs
      our view of learning.
AB  - The paper reviews research examining whether and how training can induce a
      lasting change in spinal cord function. A framework for the study of learning,
      and some essential issues in experimental design, are discussed. A core element
      involves delayed assessment under common conditions. Research has shown that
      brain systems can induce a lasting (memory-like) alteration in spinal function.
      Neurons within the lower (lumbosacral) spinal cord can also adapt when isolated
      from the brain by means of a thoracic transection. Using traditional learning
      paradigms, evidence suggests that spinal neurons support habituation and
      sensitization as well as Pavlovian and instrumental conditioning. At a
      neurobiological level, spinal systems support phenomena (e.g., long-term
      potentiation), and involve mechanisms (e.g., NMDA mediated plasticity, protein
      synthesis) implicated in brain-dependent learning and memory. Spinal learning
      also induces modulatory effects that alter the capacity for learning.
      Uncontrollable/unpredictable stimulation disables the capacity for instrumental
      learning and this effect has been linked to the cytokine tumor necrosis factor
      (TNF). Predictable/controllable stimulation enables learning and counters the
      adverse effects of uncontrollable stimulation through a process that depends upon
      brain-derived neurotrophic factor (BDNF). Finally, uncontrollable, but not
      controllable, nociceptive stimulation impairs recovery after a contusion injury.
      A process-oriented approach (neurofunctionalism) is outlined that encourages a
      broader view of learning phenomena. 

PMID- 23973907
TI  - Tetraphenylethene-based aggregation-induced emission fluorescent organic
      nanoparticles: facile preparation and cell imaging application.
AB  - Tetraphenylethene-based (TPE) aggregation-induced emission fluorescent organic
      nanoparticles (FONs) were facilely prepared via Schiff base condensation with E
      polylysine (Ply) and subsequent reduction to form stable CN covalent bond. Thus
      obtained TPE-Ply FONs were characterized by a series of techniques including
      fluorescent spectroscopy, Fourier transform infrared spectroscopy and
      transmission electron microscopy. Biocompatibility evaluation and cell uptake
      behavior of TPE-Ply FONs were further investigated to explore their potential
      biomedical application. We demonstrated that such FONs showed high water
      dispersibility, intense fluorescence, uniform morphology (100-200nm) and
      excellent biocompatibility, making them promising for cell imaging application. 

PMID- 23973908
TI  - Structural characterization of lyotropic liquid crystals containing a dendrimer
      for solubilization and release of gallic acid.
AB  - The role of 2nd generation polypropyleneimine (PPIG2) dendrimer in controlling
      the release of gallic acid (GA) as a model drug from lyotropic liquid crystal was
      explored. GA (0.2wt%) was solubilized in three types of mesophases: lamellar
      (Lalpha), cubic (space group of Ia3d, Q(G)), and reverse hexagonal (HII),
      composed of GMO and water (and d-alpha-tocopherol, or tricaprylin in the case of
      HII mesophases). Small angle X-ray scattering (SAXS) and attenuated total
      reflectance Fourier transform infrared (ATR-FTIR) along with UV spectrophotometry
      were utilized to elucidate the structure modifications and release resulting from
      the cosolubilization of GA and PPIG2. Solubilization of PPIG2 into Lalpha and
      Q(G) phases caused transformation of both structures to HII. The diffusion of GA
      out of the mesophases was found to be dependent on water content and PPIG2
      concentration. Rapid release from Lalpha+PPIG2 and Q(G)+PPIG2 mesophases was
      recorded. The release from both HII mixtures (with d-alpha-tocopherol and
      tricaprylin) was shown to be dependent on the type of oil. Release studies
      conducted for 72h showed that GA release can be modulated and sustained by the
      presence of PPIG2, supposedly due to the electrostatic interactions between the
      dendrimer and the drug molecule. 

PMID- 23973909
TI  - Facile preparation of Artemisia argyi oil-loaded antibacterial microcapsules by
      hydroxyapatite-stabilized Pickering emulsion templating.
AB  - Artemisia argyi oil (AAO)-loaded antibacterial microcapsules with hydroxyapatite
      (HAp)/poly(melamine formaldehyde) (PMF) hybrid shells were facilely prepared by
      oil-in-water (O/W) Pickering emulsion templating. AAO-in-water emulsions were
      stabilized using HAp nanoparticles as the particulate emulsifier. The hybrid
      shells were fabricated by in situ polymerization of melamine formaldehyde pre
      polymer (pre-MF) at the interface of the O/W Pickering emulsions. The prepared
      microcapsules were characterized in terms of size, morphology, component and
      thermal stability using scanning electronic microscope (SEM), Fourier transform
      infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), respectively.
      Moreover, both in vitro release and antimicrobial activity of the microcapsules
      were also evaluated. The results showed that the AAO-loaded microcapsules with
      HAp/PMF shells had a spherical shape and a rough surface. The microcapsules
      maintained excellent performances in the thermal stability, controlled release
      activity, antimicrobial effect and long-term antimicrobial activity. The release
      curves of AAO from the microcapsules could be well described by Higuchi kinetic
      model. The microcapsules may find applications as antibacterial agents in the
      areas of textiles, leather, rubber and coatings. In situ polymerization based on
      Pickering emulsion droplets opens up a new route to prepare a variety of hybrid
      microcapsules with a core-shell structure. 

PMID- 23973910
TI  - Selective adsorption of bilirubin against albumin to oxidized single-wall carbon
      nanohorns.
AB  - Bilirubin adsorption capacities of single-wall carbon nanohorns (SWNHs) are
      investigated to develop an efficient adsorbent in plasma apheresis. Pristine,
      thermally oxidized and H2O2-oxidized SWNHs are examined and it is demonstrated
      that higher oxidization levels of the SWNHs enhance bilirubin adsorption capacity
      owing to increase in their dispersibility and formation of nanoscaled holes on
      the SWNH walls. Under co-existance of albumin molecules, the bilirubin adsorption
      capacity of the SWNHs increases with the oxidation level whereas the albumin
      adsorption capacity is kept small. Bilirubin is selectively adsorbed to the
      SWNHs, especially to the SWNHs with high oxidation levels, against albumin. This
      selectivity is maintained under high-concentrations of albumin in the near
      clinical environment. 

PMID- 23973911
TI  - A sensitivity analysis using alternative toxic equivalency factors to estimate
      U.S. dietary exposures to dioxin-like compounds.
AB  - EPA recommends sensitivity analyses when applying the toxic equivalency factor
      (TEF) method to evaluate exposures to dioxin-like compounds (DLCs). Applying the
      World Health Organization's (WHO) 2005 TEF values and estimating average U.S.
      daily dietary intakes of 25 DLCs from eight food categories, we estimate a toxic
      equivalency (TEQ) intake of 23 pg/day. Among DLCs, PCB 126 (26%) and 1,2,3,7,8
      PeCDD (23%) dominate TEQ intakes. Among food categories, milk (14%), other dairy
      (28%), beef (25%), and seafood (18%) most influenced TEQ intakes. We develop two
      approaches to estimate alternative TEF values. Based on WHO's assumption
      regarding TEF uncertainty, Approach1 estimates upper and lower TEFs for each DLC
      by multiplying and dividing, respectively, its individual TEF by +/- half a log.
      Based on compiled empirical ranges of relative potency estimates, Approach2 uses
      percentile values for individual TEFs. Total TEQ intake estimates using the lower
      and upper TEFs based on Approach1 were 8 and 68 pg TEQ/day, respectively. The
      25th and 75th percentile TEFs from Approach2 yielded 12 and 28 pg TEQ/day,
      respectively. The influential DLCs and food categories remained consistent across
      alternative TEFs, except at the 90th percentile using Approach2. We highlight the
      need for developing underlying TEF probability distributions.

PMID- 23973913
TI  - Modelling the learning of biomechanics and visual planning for decision-making of
      motor actions.
AB  - Recent experiments showed that the bio-mechanical ease and end-point stability
      associated to reaching movements are predicted prior to movement onset, and that
      these factors exert a significant influence on the choice of movement. As an
      extension of these results, here we investigate whether the knowledge about
      biomechanical costs and their influence on decision-making are the result of an
      adaptation process taking place during each experimental session or whether this
      knowledge was learned at an earlier stage of development. Specifically, we
      analysed both the pattern of decision-making and its fluctuations during each
      session, of several human subjects making free choices between two reaching
      movements that varied in path distance (target relative distance), biomechanical
      cost, aiming accuracy and stopping requirement. Our main result shows that the
      effect of biomechanics is well established at the start of the session, and that,
      consequently, the learning of biomechanical costs in decision-making occurred at
      an earlier stage of development. As a means to characterise the dynamics of this
      learning process, we also developed a model-based reinforcement learning model,
      which generates a possible account of how biomechanics may be incorporated into
      the motor plan to select between reaching movements. Results obtained in
      simulation showed that, after some pre-training corresponding to a motor babbling
      phase, the model can reproduce the subjects' overall movement preferences.
      Although preliminary, this supports that the knowledge about biomechanical costs
      may have been learned in this manner, and supports the hypothesis that the
      fluctuations observed in the subjects' behaviour may adapt in a similar fashion. 

PMID- 23973914
TI  - Infectious salmon anemia virus (ISAV) replication is transiently inhibited by
      Atlantic salmon type I interferon in cell culture.
AB  - Infectious salmon anemia virus (ISAV) is a piscine orthomyxovirus, which causes
      multisystemic disease in farmed Atlantic salmon that may result in large losses.
      Previous work has suggested that ISAV is able to resist the antiviral state
      induced in cells by type I interferon (IFN). These studies were, however, mainly
      based on cytopathic effect (CPE) reduction assays. Here we have investigated the
      antiviral activity of Atlantic salmon IFNa1, IFNb and IFNc against ISAV using
      quantitative PCR (qPCR) of segment 6, Western blot analysis of ISAV proteins and
      viral yield reduction assays, in addition to CPE reduction assays. Antiviral
      effects of IFNs were tested against the high virulent strain ISAV4 and the low
      virulent strain ISAV7 both at the optimum growth temperature 15 degrees C and at
      20 degrees C. As expected, IFNa1 showed little protection against CPE development
      in cells after infection with both strains at 15 degrees C. However, the qPCR and
      Western blot analysis clearly showed strong inhibition of replication of the
      virus strains by IFNa1 between 24 and 72h after infection. The inhibitory effect
      declined four to five days post-infection, which explains the low protection
      against CPE development 7-10 days later. At 20 degrees C, IFNa1 showed strong
      protection against CPE development, probably due to slower virus growth. IFNc
      showed similar antiviral activity as IFNa1 against ISAV4 while IFNb showed lower
      activity. There were observed differences between ISAV4 and ISAV7 both with
      respect inhibition by IFNa1 and ability to induce the two IFN-inducible antiviral
      effector proteins, Mx and ISG15, which may be related to differences in virulence
      properties and/or adaption to growth in cell culture.

PMID- 23973915
TI  - Virulence determination and molecular features of peach latent mosaic viroid
      isolates derived from phenotypically different peach leaves: a nucleotide
      polymorphism in L11 contributes to symptom alteration.
AB  - Symptoms of chlorosis along leaf edges (chlorosis-edge), along leaf veins
      (chlorosis-vein) and yellowing on peach leaves have been observed for a long
      history in the field, while the pathological factor(s) responsible for these
      symptoms remained unknown. Peach latent mosaic viroid (PLMVd) was detected in the
      leaves collected from three unique phenotypic peach trees showing above mentioned
      symptoms. The obtained PLMVd isolates were subjected to population structure
      analyses and biological assays to evaluate their pathogenicity on peach seedlings
      in an effort to elucidate the relationship between the PLMVd and the symptoms
      observed on peach trees in China. In addition, molecular features of PLMVd
      isolates were analyzed to obtain some insight into the structure-function
      relationships of this viroid. The results revealed that the symptoms of chlorosis
      edge and yellowing were indeed incited by PLMVd, and a direct link between the
      nucleotide polymorphisms and the symptoms of yellowing and chlorosis-edge was
      established, i.e. residue U338 responsible for the yellowish symptom and C338
      responsible for the chlorosis-edge symptom. This study provides an additional
      proof to endorse a previous proposal that PLMVd pathogenicity determinants reside
      in L11. The illustrative etiology of the disease, visualization of the symptoms
      progression and identification of the unique single nucleotide polymorphism
      possibly involved in the symptom induction will significantly increase
      understanding of the pathogenic mechanisms of PLMVd and will help in designing
      control strategies for the resulting disease.

PMID- 23973916
TI  - Dynamics of pathologic clot formation: a mathematical model.
AB  - Recent studies have provided evidence of a significant role of the Hageman factor
      in pathologic clot formation. Since auto-activation of the Hageman factor
      triggers the intrinsic coagulation pathway, we study the dynamics of pathologic
      clot formation considering the intrinsic pathway as the predominant mechanism of
      this process. Our methodological approach to studying the dynamics of clot
      formation is based on mathematical modelling. Activation of the blood coagulation
      cascade, particularly its intrinsic pathway, is known to involve platelets.
      Therefore, equations accounting for the effects of activated platelets on the
      intrinsic pathway activation are included in our model. This brings about a
      considerable increase in the values of kinetic constants involved in the model of
      the principal biochemical processes resulting in clot formation. The purpose of
      this study is to elucidate the mechanism of pathologic clot formation. Since the
      time window of thrombolysis is 3-6h, we hypothesize that in many cases the rate
      of pathologic clot formation is much lower than that of haemostatic clot. This
      assumption is used to simplify the mathematical model and to estimate kinetic
      constants of biochemical reactions that initiate pathologic clot formation. The
      insights we gained from our mathematical model may lead to new approaches to the
      prophylaxis of pathologic clot formation. We believe that one of the most
      efficient ways to prevent pathologic clot formation is simultaneous inhibition of
      activated factors XII and XI. 

PMID- 23973912
TI  - Nanopreparations to overcome multidrug resistance in cancer.
AB  - Multidrug resistance is the most widely exploited phenomenon by which cancer
      eludes chemotherapy. Broad variety of factors, ranging from the cellular ones,
      such as over-expression of efflux transporters, defective apoptotic machineries,
      and altered molecular targets, to the physiological factors such as higher
      interstitial fluid pressure, low extracellular pH, and formation of irregular
      tumor vasculature are responsible for multidrug resistance. A combination of
      various undesirable factors associated with biological surroundings together with
      poor solubility and instability of many potential therapeutic small & large
      molecules within the biological systems and systemic toxicity of chemotherapeutic
      agents has necessitated the need for nano-preparations to optimize drug delivery.
      The physiology of solid tumors presents numerous challenges for successful
      therapy. However, it also offers unique opportunities for the use of
      nanotechnology. Nanoparticles, up to 400 nm in size, have shown great promise for
      carrying, protecting and delivering potential therapeutic molecules with diverse
      physiological properties. In this review, various factors responsible for the MDR
      and the use of nanotechnology to overcome the MDR, the use of spheroid culture as
      well as the current technique of producing microtumor tissues in vitro are
      discussed in detail.

PMID- 23973917
TI  - Monitoring wound healing of elastic cartilage using multiphoton microscopy.
AB  - OBJECTIVE: To demonstrate the ability of multiphoton microscopy (MPM) for
      monitoring wound healing of elastic cartilage. METHOD: In a rabbit ear model,
      four cartilage specimen groups at 1-day, 1-, 4-, 20-week healing time points as
      well as a normal elastic cartilage were examined with MPM without using labeling
      agents. MPM images at wound margins were obtained from specimens at different
      healing stages, compared with the Hematoxylin and Eosin (H&E) stained images.
      Image analysis was performed to characterize the collagen morphology for
      quantifying the wound healing progression of elastic cartilage. RESULTS: MPM
      provided high-resolution images of elastic cartilage at varying depths.
      Comparisons of the images of specimens at different healing stages show obvious
      cell growth and matrix deposition. The results are consistent with the
      histological results. Moreover, quantitative analysis results show significant
      alteration in the collagen cavity size or collagen orientation index during wound
      healing of elastic cartilage, indicating the possibility to act as indicators for
      monitoring wound healing. CONCLUSION: Our results suggested that MPM has the
      ability to monitor the wound healing progression of elastic cartilage, based on
      the visualization of cell growth and proliferation and quantitative
      characterization of collagen morphology during wound healing.

PMID- 23973918
TI  - How to make a successful transition from fellowship to faculty in an academic
      medical center.

PMID- 23973919
TI  - Atg16l1 is required for autophagy in intestinal epithelial cells and protection
      of mice from Salmonella infection.
AB  - BACKGROUND & AIMS: Intestinal epithelial cells aid in mucosal defense by
      providing a physical barrier against entry of pathogenic bacteria and secreting
      antimicrobial peptides (AMPs). Autophagy is an important component of immune
      homeostasis. However, little is known about its role in specific cell types
      during bacterial infection in vivo. We investigated the role of autophagy in the
      response of intestinal epithelial and antigen-presenting cells to Salmonella
      infection in mice. METHODS: We generated mice deficient in Atg16l1 in epithelial
      cells (Atg16l1(f/f) * Villin-cre) or CD11c(+) cells (Atg16l1(f/f) * CD11c-cre);
      these mice were used to assess cell type-specific antibacterial autophagy. All
      responses were compared with Atg16l1(f/f) mice (controls). Mice were infected
      with Salmonella enterica serovar typhimurium; cecum and small-intestine tissues
      were collected for immunofluorescence, histology, and quantitative reverse
      transcription polymerase chain reaction analyses of cytokines and AMPs.
      Modulators of autophagy were screened to evaluate their effects on antibacterial
      responses in human epithelial cells. RESULTS: Autophagy was induced in small
      intestine and cecum after infection with S typhimurium, and required Atg16l1. S
      typhimurium colocalized with microtubule-associated protein 1 light chain 3beta
      (Map1lc3b or LC3) in the intestinal epithelium of control mice but not in
      Atg16l1(f/f) * Villin-cre mice. Atg16l1(f/f) * Villin-cre mice also had fewer
      Paneth cells and abnormal granule morphology, leading to reduced expression of
      AMPs. Consistent with these defective immune responses, Atg16l1(f/f) * Villin-cre
      mice had increased inflammation and systemic translocation of bacteria compared
      with control mice. In contrast, we observed few differences between Atg16l1(f/f)
      * CD11c-cre and control mice. Trifluoperazine promoted autophagy and bacterial
      clearance in HeLa cells; these effects were reduced upon knockdown of ATG16L1.
      CONCLUSIONS: Atg16l1 regulates autophagy in intestinal epithelial cells and is
      required for bacterial clearance. It also is required to prevent systemic
      infection of mice with enteric bacteria.

PMID- 23973920
TI  - Association between high-normal levels of alanine aminotransferase and risk
      factors for atherogenesis.
AB  - BACKGROUND & AIMS: Liver disease has been associated with cardiovascular
      disorders, but little is known about the relationship between serum levels of
      alanine aminotransferase (ALT) and markers of atherogenesis. We investigated the
      relationship between low-normal and high-normal levels of ALT and an extended
      panel of cardiovascular risk factors among individuals with no known diseases in
      a primary care setting. METHODS: We performed a retrospective analysis of data
      collected from 6442 asymptomatic patients at wellness visits to a primary care
      setting in central Virginia from 2010 through 2011. Serum levels of ALT were
      compared with levels of lipids and lipoproteins, as well as metabolic,
      inflammatory, and coagulation-related factors associated with risk for
      cardiovascular disease. RESULTS: Serum levels of ALT were higher than 40 IU/L in
      12% of subjects, and in the high-normal range (19-40 IU/L in women and 31-40 IU/L
      in men) in 25% of subjects. ALT level was associated with the apolipoprotein B
      level, concentration and particle size of very-low-density lipoproteins,
      concentration of low-density lipoprotein (LDL) particles (LDL-P), and percentages
      of small dense LDL (sdLDL) and sdLDL-cholesterol (sdLDL-C) (P < .0001 for all). A
      high-normal level of ALT was associated with higher levels of LDL-C, LDL-P, sdLDL
      C, and sdLDL particles (P < .001 for all). These effects were independent of age,
      body mass index, and hyperinsulinemia. Increasing levels of ALT and fasting
      hyperinsulinemia (>12 MUU/mL) synergized with increasing levels of triglycerides,
      very-low-density lipoprotein particles, LDL-P, sdLDL-C, and percentage of sdLDL
      C. Levels of APOA1, high-density lipoprotein-cholesterol, and high-density
      lipoprotein-class 2 were associated inversely with serum level of ALT (P < .0001
      for all). CONCLUSIONS: In an analysis of asymptomatic individuals, increased
      serum levels of ALT (even high-normal levels) are associated with markers of
      cardiovascular disease.

PMID- 23973921
TI  - Hepatitis C virus replication in mouse cells is restricted by IFN-dependent and 
      independent mechanisms.
AB  - BACKGROUND & AIMS: Current treatment strategies for hepatitis C virus (HCV)
      infection include pegylated interferon (IFN)-alfa and ribavirin. Approximately
      50% of patients control HCV infection after treatment, but the broad range of
      patients' outcomes and responses to treatment, among all genotypes, indicates a
      role for host factors. Although the IFN system is important in limiting HCV
      replication, the virus has evolved mechanisms to circumvent the IFN response.
      However, direct, IFN-independent antiviral processes also might help control HCV
      replication. We examined the role of IFN-independent responses against HCV
      replication. METHODS: We analyzed replication of the subgenomic JFH1 replicon in
      embryonic fibroblasts and primary hepatocytes from mice with disruptions in genes
      encoding factors in the IFN-dependent and alternative antiviral pathways (signal
      transducers and activators of transcription 1 [STAT1], protein kinase R,
      interferon regulatory factors (IRF) IRF-1, IRF-3, IRF-5, IRF-7, mitochondrial
      antiviral signaling molecule [MAVS], and IFN receptor [IFNAR]). We also assessed
      the effects of expression of these factors by mouse primary hepatocytes on HCV
      replication. RESULTS: In addition to IRF-3- and IFN-mediated antiviral responses,
      IFN-independent, but IRF-1- and IRF-5-dependent mechanisms, restrict HCV
      replication in mouse embryonic fibroblasts. In primary hepatocytes these IFN
      independent require MAVS and IRF-1. CONCLUSIONS: HCV replication is limited by
      interferon-mediated pathways as well pathways that are independent of type I
      IFNs. IRF1 and IRF5 control IFN-independent signaling events that lead to
      antiviral responses. We observed antiviral roles of IRF1 and IRF5 that were IFN
      independent and cell-type specific. These mechanisms are important in controlling
      viruses that interfere with the IFN signaling because cells retain the ability to
      induce functional but local antiviral states through expression of interferon
      stimulated genes.

PMID- 23973922
TI  - Human umbilical cord blood mesenchymal stem cells reduce colitis in mice by
      activating NOD2 signaling to COX2.
AB  - BACKGROUND & AIMS: Decreased levels or function of nucleotide-binding
      oligomerization domain 2 (NOD2) are associated with Crohn's disease. NOD2
      regulates intestinal inflammation, and also is expressed by human umbilical cord
      blood-derived mesenchymal stem cells (hUCB-MSCs), to regulate their
      differentiation. We investigated whether NOD2 is required for the anti
      inflammatory activities of MSCs in mice with colitis. METHODS: Colitis was
      induced in mice by administration of dextran sulfate sodium or trinitrobenzene
      sulfonic acid. Mice then were given intraperitoneal injections of NOD2-activated
      hUCB-MSCs; colon tissues and mesenteric lymph nodes were collected for histologic
      analyses. A bromodeoxyuridine assay was used to determine the ability of hUCB
      MSCs to inhibit proliferation of human mononuclear cells in culture. RESULTS:
      Administration of hUCB-MSCs reduced the severity of colitis in mice. The anti
      inflammatory effects of hUCB-MSCs were greatly increased by activation of NOD2 by
      its ligand, muramyl dipeptide (MDP). Administration of NOD2-activated hUCB-MSCs
      increased anti-inflammatory responses in colons of mice, such as production of
      interleukin (IL)-10 and infiltration by T regulatory cells, and reduced
      production of inflammatory cytokines. Proliferation of mononuclear cells was
      inhibited significantly by co-culture with hUCB-MSCs that had been stimulated
      with MDP. MDP induced prolonged production of prostaglandin (PG)E2 in hUCB-MSCs
      via the NOD2-RIP2 pathway, which suppressed proliferation of mononuclear cells
      derived from hUCB. PGE2 produced by hUCB-MSCs in response to MDP increased
      production of IL-10 and T regulatory cells. In mice, production of PGE2 by MSCs
      and subsequent production of IL-10 were required to reduce the severity of
      colitis. CONCLUSIONS: Activation of NOD2 is required for the ability of hUCB-MSCs
      to reduce the severity of colitis in mice. NOD2 signaling increases the ability
      of these cells to suppress mononuclear cell proliferation by inducing production
      of PGE2.

PMID- 23973924
TI  - Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced
      proliferation in experimental pituitary hyperplasia.
AB  - Toll like receptor 4 (TLR4) has been characterized for its ability to recognize
      bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or
      inflammatory processes might contribute to the progression of pituitary tumors,
      we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph
      proliferation in primary cultures from experimental pituitary tumors, and
      examined the involvement of PI3K-Akt and NF-kappaB activation in this effect. In
      addition, the role of 17beta-estradiol as a possible modulator of LPS-induced PRL
      cell proliferation was further investigated. In estrogen-induced hyperplasic
      pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin
      failed to increase the number of lactotrophs taking up BrdU in normal
      pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced
      LPS-induced lactotroph proliferation, suggesting a functional role of this
      receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release
      in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was
      revealed at the plasma membrane of tumoral lactotrophs, without changes noted in
      the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in
      TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and
      NF-kappaB after an LPS challenge, as assessed by western blotting. The TLR4/PRL
      and PRL/NF-kappaB co-localization was also corroborated by immunofluorescence and
      the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6
      release was revealed through the PI3K inhibitor Ly-294002. In addition, 17beta
      estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation
      and IL-6 release. Collectively these results demonstrate the presence of
      functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries,
      which responded to the proliferative stimulation and IL-6 release induced by LPS
      through TLR4/CD14, with a contribution of the PI3K-Akt and NF-kappaB signaling
      pathways.

PMID- 23973923
TI  - The spectrum of achalasia: lessons from studies of pathophysiology and high
      resolution manometry.
AB  - High-resolution manometry and recently described analysis algorithms, summarized
      in the Chicago Classification, have increased the recognition of achalasia. It
      has become apparent that the cardinal feature of achalasia, impaired lower
      esophageal sphincter relaxation, can occur in several disease phenotypes: without
      peristalsis, with premature (spastic) distal esophageal contractions, with
      panesophageal pressurization, or with peristalsis. Any of these phenotypes could
      indicate achalasia; however, without a disease-specific biomarker, no manometric
      pattern is absolutely specific. Laboratory studies indicate that achalasia is an
      autoimmune disease in which esophageal myenteric neurons are attacked in a cell
      mediated and antibody-mediated immune response against an uncertain antigen. This
      autoimmune response could be related to infection of genetically predisposed
      subjects with herpes simplex virus 1, although there is substantial heterogeneity
      among patients. At one end of the spectrum is complete aganglionosis in patients
      with end-stage or fulminant disease. At the opposite extreme is type III
      (spastic) achalasia, which has no demonstrated neuronal loss but only impaired
      inhibitory postganglionic neuron function; it is often associated with
      accentuated contractility and could be mediated by cytokine-induced alterations
      in gene expression. Distinct from these extremes is progressive plexopathy, which
      likely arises from achalasia with preserved peristalsis and then develops into
      type II achalasia and then type I achalasia. Variations in its extent and rate of
      progression are likely related to the intensity of the cytotoxic T-cell assault
      on the myenteric plexus. Moving forward, we need to integrate the knowledge we
      have gained into treatment paradigms that are specific for individual phenotypes
      of achalasia and away from the one-size-fits-all approach. 

PMID- 23973926
TI  - Clonidine and botulinum toxin: a tale of two treatments.

PMID- 23973925
TI  - Limited life expectancy among a subgroup of medicare beneficiaries receiving
      screening colonoscopies.
AB  - BACKGROUND & AIMS: Life expectancy is an important consideration when assessing
      appropriateness of preventive programs for older individuals. Most studies on
      this subject have used age cutoffs as a proxy for life expectancy. We analyzed
      patterns of utilization of screening colonoscopy in Medicare enrollees by using
      estimated life expectancy. METHODS: We used a 5% random national sample of
      Medicare claims data to identify average-risk patients who underwent screening
      colonoscopies from 2008 to 2010. Colonoscopies were considered to be screening
      colonoscopies in the absence of diagnoses for nonscreening indications, which
      were based on either colonoscopies or any claims in the preceding 3 months. We
      estimated life expectancies by using a model that combined age, sex, and
      comorbidity. Among patients who underwent screening colonoscopies, we calculated
      the percentage of those with life expectancies <10 years. RESULTS: Among the
      57,597 Medicare beneficiaries 66 years old or older who received at least 1
      screening colonoscopy, 24.8% had an estimated life expectancy of <10 years. There
      was a significant positive association between total Medicare per capita costs in
      hospital referral regions and the proportion of patients with limited life
      expectancies (<10 years) at the time of screening colonoscopy (R = 0.25; P <
      .001, Pearson correlation test). In a multivariable analysis, men were
      substantially more likely than women to have limited life expectancy at the time
      of screening colonoscopy (odds ratio, 2.25; 95% confidence interval, 2.16-2.34).
      CONCLUSIONS: Nearly 25% of Medicare beneficiaries, especially men, had life
      expectancies <10 years at the time of screening colonoscopies. Life expectancy
      should therefore be incorporated in decision-making for preventive services.

PMID- 23973927
TI  - Physiological and functional characteristics of Propionibacterium strains of the
      poultry microbiota and relevance for the development of probiotic products.
AB  - The prevention and control of pathogens colonization through probiotics
      administration in poultry feeding is of increasing interest. The genus
      Propionibacterium is an attractive candidate for the development of probiotic
      cultures as they produce short chain fatty acids (SCFA) by carbohydrates
      fermentation. The presence of strains of this genus in hens of conventional
      production systems and backyard hens was investigated. Propionibacteria were
      isolated from the intestine and identified by physiological and biochemical
      tests. PCR amplification of the 16S rRNA gene of the isolates was performed and
      products were compared with sequences from databases. The presence of the genus
      Propionibacterium was demonstrated in 26% of hens and Propionibacterium
      acidipropionici and Propionibacterium avidum were the identified species. A
      comparative study of their physiological and functional characteristics was
      performed. P. acidipropionici strains were the most resistant to in vitro
      gastrointestinal digestion, but the adhesion to intestinal tissue was strain
      dependent. Some differences were found between both species with respect to their
      growth and SCFA production in an in vitro cecal water model, but all the strains
      were metabolically active. The production of SCFA in cecal slurries inoculated
      with the strain P. acidipropionici LET 105 was 30% higher than in non-inoculated
      samples. SCFA concentrations obtained were high enough to inhibit Salmonella
      enterica serovar Enteritidis when assayed in a cecal water model. P.
      acidipropionici LET 105 was also able to compete with Salmonella for adhesion
      sites on the intestinal mucosa in ex vivo assays. Results contribute to the
      knowledge of the species diversity of the genus Propionibacterium in the
      intestine of poultry and provide evidence of their potential for probiotics
      products development. 

PMID- 23973928
TI  - 'Big, strong and healthy'. Young children's identification of food and drink that
      contribute to healthy growth.
AB  - Growing awareness of the importance of healthy diet in early childhood makes it
      important to chart the development of children's understanding of food and drink.
      This study aimed to document young children's evaluation of food and drink as
      healthy, and to explore relationships with socioeconomic status, family eating
      habits, and children's television viewing. Data were gathered from children aged
      3-5 years (n=172) in diverse socioeconomic settings in Ireland, and from their
      parents. Results demonstrated that children had very high levels of ability to
      identify healthy foods as important for growth and health, but considerably less
      ability to reject unhealthy items, although knowledge of these increased
      significantly between ages 3 and 5. Awareness of which foods were healthy, and
      which foods were not, was not related to family socioeconomic status, parent or
      child home eating habits, or children's television viewing. Results highlighted
      the importance of examining young children's response patterns, as many of the
      youngest showed a consistent 'yes bias'; however, after excluding these
      responses, the significant findings remained. Findings suggest it is important to
      teach children about less healthy foods in the preschool years.

PMID- 23973929
TI  - A bidirectional crosstalk between iNKT cells and adipocytes mediated by leptin
      modulates susceptibility for T cell mediated hepatitis.
AB  - BACKGROUND & AIMS: Immunometabolism is an emerging field of clinical
      investigation due to the obesity epidemic worldwide. A reciprocal involvement of
      immune mediators in the body energy metabolism has been recognized for years, but
      is only partially understood. We hypothesized that the adipokine leptin could
      provide an important modulator of iNKT cells. METHODS: The expression of leptin
      receptor (LR) on resting and activated iNKT cells was measured by flow cytometry.
      FACS-sorted hepatic iNKT cells were stimulated with anti-CD3/CD28Ab coated beads
      in the absence or presence of a neutralizing anti-leptin Ab. Furthermore, we
      evaluated the outcome of LR blocking nanobody treatment in ConA induced hepatitis
      and towards metabolic parameters in WT and iNKT cell deficient mice. RESULTS: The
      LR is expressed on iNKT cells and leptin suppresses iNKT cell proliferation and
      cytokine production in vitro. LR deficient iNKT cells are hyper-responsive
      further enforcing the role of leptin as an important inhibitor of iNKT cell
      function. Consistently, in vivo blockade of LR signaling exacerbated ConA
      hepatitis in wild-type but not in iNKT cell deficient mice, through both Janus
      kinase (JAK)2 and mitogen-activated protein kinase (MAPK) dependent mechanisms.
      Moreover, LR inhibition altered fat pad features and was accompanied by insulin
      resistance, only in wild-type mice. Curiously, this interaction was strictly
      dependent on MAPK mediated LR signaling in iNKT cells and uncoupled from the more
      central effects of leptin. CONCLUSIONS: Our data support a new concept of immune
      regulation by which leptin protects towards T cell mediated hepatitis via
      modulation of iNKT cells.

PMID- 23973930
TI  - Identification of naive HCV-1 patients with chronic hepatitis who may benefit
      from dual therapy with peg-interferon and ribavirin.
AB  - BACKGROUND & AIMS: The pool of HCV genotype 1 patients likely to be cured by peg
      interferon and ribavirin remains to be quantified. METHODS: In 1045 patients
      treated with peg-interferon and ribavirin, two therapeutic strategies were
      confronted: the first one evaluated only baseline variables associated with
      sustained virological response (SVR), and the second one included the rapid
      virologic response (RVR) in addition to baseline predictors. An 80% SVR rate was
      the threshold to retain a strategy as clinically relevant. RESULTS: Overall, 414
      patients (39.6%) attained SVR. In the first strategy, the hierarchy of features
      independently associated with SVR was IL28B CC genotype (OR 5.082; CI 3.637
      7.101), low (<400,000 IU) viremia (OR 2.907; CI 2.111-4.004), F0-F2 fibrosis (OR
      1.631; CI 1.122-2.372) and type 2 diabetes (OR 0.528; CI 0.286-0.972). In the
      alternative strategy, SVR was associated with RVR (OR 6.273; CI 4.274-9.208),
      IL28B CC genotype (OR 3.306; CI 2.301-4.751), low viremia (OR 2.175; CI 1.542
      3.070), and F0-F2 fibrosis (OR 1.506; CI 1.012-2.242). Combining the favorable
      baseline variables, the rates of SVR ranged from 42.4% to 83.3%, but only 66
      patients (6.3%, overall) with all predictors could be anticipated to reach the
      >80% SVR threshold. Only 26.6% of no-RVR patients attained SVR. Among the 255 RVR
      patients, the likelihood of SVR was 61.8% in those with unfavorable predictors,
      80% in the presence of a single predictor, and 100% when both predictors were
      present. By using this model, 200 patients (19.1%) were predicted to have an 80%
      chance of being cured with dual therapy. CONCLUSIONS: A consistent subset of
      naive HCV-1 patients, identified by some baseline characteristics and RVR, may
      benefit from dual treatment with peg-interferon and ribavirin.

PMID- 23973931
TI  - Is there sufficient evidence to recommend antiviral therapy in hepatitis C?
AB  - While patients with chronic hepatitis C virus (HCV) infection are treated in
      order to prevent liver-related morbidity and mortality, we rely on sustained
      virological response (SVR) as a virological biomarker to evaluate treatment
      efficacy in both clinical practice as well as in drug development. However,
      conclusive evidence for the clinical benefit of antiviral therapy or validity of
      SVR as surrogate marker, as derived from trials randomizing patients to a
      treatment or control arm, is lacking. In fact, the Hepatitis C Antiviral Long
      term Treatment Against Cirrhosis (HALT-C) trial recently showed an increased
      mortality rate among interferon-treated patients compared to untreated controls.
      Consequently, the recommendation to treat patients with chronic HCV infection was
      challenged. Here, we argue that the possible harmful effect of long-term low-dose
      pegylated interferon mono therapy, as was observed in the HALT-C trial cohort,
      cannot be extrapolated to potentially curative short-term treatment regimens.
      Furthermore, we discuss SVR as a surrogate biomarker, based on numerous studies
      which indicated an association between SVR and improvements in health-related
      quality of life, hepatic inflammation and fibrosis, and portal pressure as well
      as a reduced risk for hepatocellular carcinoma (HCC), liver failure and
      mortality. 

PMID- 23973932
TI  - Limited value of plasma cytokeratin-18 as a biomarker for NASH and fibrosis in
      patients with non-alcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: Liver biopsy is the only reliable way of diagnosing and
      staging NASH but its invasive nature limits its use. Plasma caspase-generated
      cytokeratin-18 fragments (CK-18) have been proposed as a non-invasive
      alternative. We studied its clinical value in a large multiethnic NAFLD
      population and examined its relationship to clinical/metabolic/histological
      parameters. METHODS: 424 middle-aged subjects in whom we measured adipose tissue,
      liver and muscle insulin resistance (IR), liver fat by MRS (n=275) and histology
      (n=318). RESULTS: Median CK-18 were elevated in patients with vs. without NAFLD
      by MRS (209 [IQR: 137-329] vs. 122 [IQR: 98-155]U/L) or with vs. without NASH
      (232 [IQR: 151-387] vs. 170 [IQR: 135-234]U/L, both p<0.001). Plasma CK-18 raised
      significantly with any increase in steatosis, inflammation and fibrosis, but
      there was a significant overlap across disease severity. The CK-18 AUROC to
      predict NAFLD, NASH or fibrosis were 0.77 (95% CI=0.71-0.84), 0.65 (95% CI=0.59
      0.71) and 0.68 (95% CI=0.61-0.75), respectively. The overall
      sensitivity/specificity for NAFLD, NASH and fibrosis were 63% (57-70%)/83% (69
      92%), 58% (51-65%)/68% (59-76%) and 54% (44-63%)/85% (75-92%), respectively. CK
      18 correlated most strongly with ALT (r=0.57, p<0.0001) and adipose tissue IR
      (insulin-suppression of FFA: r=-0.43; p<0.001), less with steatosis, lobular
      inflammation and fibrosis (r=0.28-0.34, all p<0.001), but not with ballooning,
      BMI, metabolic syndrome or T2DM. CONCLUSIONS: Plasma CK-18 has a high specificity
      for NAFLD and fibrosis, but its limited sensitivity makes it inadequate as a
      screening test for staging NASH. Whether combined as a diagnostic panel with
      other biomarkers or clinical/laboratory tests may prove useful requires further
      study.

PMID- 23973933
TI  - Hirmi Valley liver disease: a disease associated with exposure to pyrrolizidine
      alkaloids and DDT.
AB  - BACKGROUND & AIMS: Hirmi Valley liver disease was first reported in 2001 in
      Tigray, Ethiopia. 591 cases, including 228 deaths, were reported up to December
      2009. The pyrrolizidine alkaloid acetyllycopsamine was detected in stored grain
      and residents reported adding the pesticide DDT
      (dichlorodiphenyldichloroethylene) directly to their food stores. We aimed to
      characterise the clinical features of the disease, and explore the role of these
      chemicals in its aetiology. METHODS: 32 cases were examined and full clinical
      histories taken. Nine cases underwent liver biopsy in hospitals. Serum and urine
      samples were collected from cases and controls. Urine was analysed for
      acetyllycopsamine by UPLC-MS. Total DDT in serum was measured by ELISA.
      Hepatotoxicity of DDT and acetyllycopsamine alone or in combination was explored
      in C57BL/6J mice. RESULTS: Clinical presentation included epigastric pain,
      abdominal swelling, bloody diarrhoea, hepatomegaly, splenomegaly, and ascites.
      Histology revealed acute injury characterised by centrilobular necrosis or
      chronic injury with bile ductular reaction, cytomegaly and fibrosis but no
      hepatic vein occlusion. Acetyllycopsamine was detected in urine samples taken in
      the affected area with significantly greater concentrations in 45 cases than in
      43 controls (p=0.02). High levels of DDT (>125 ppb) were detected in 78% of serum
      samples. In mice, DDT (3 * 75 mg/kg) significantly increased the hepatotoxicity
      (plasma ALT, p=0.0065) of acetyllycopsamine (750 mg/kg), and in combination
      induced liver pathology similar to Hirmi Valley liver disease including
      centrilobular necrosis and cytomegaly. CONCLUSIONS: This novel form of disease
      appears to be caused by co-exposure to acetyllycopsamine and DDT.

PMID- 23973934
TI  - Highly sensitive detection of molecular interactions with plasmonic optical fiber
      grating sensors.
AB  - Surface Plasmon resonance (SPR) optical fiber biosensors constitute a
      miniaturized counterpart to the bulky prism configuration and offer remote
      operation in very small volumes of analyte. They are a cost-effective and
      relatively straightforward technique to yield in situ (or even possibly in vivo)
      molecular detection. The biosensor configuration reported in this work uses
      nanometric-scale gold-coated tilted fiber Bragg gratings (TFBGs) interrogated by
      light polarized radially to the optical fiber outer surface, so as to maximize
      the optical coupling with the SPR. These gratings were recently associated to
      aptamers to assess their label-free biorecognition capability in buffer and serum
      solutions. In this work, using the well-acknowledged biotin-streptavidin pair as
      a benchmark, we go forward in the demonstration of their unique sensitivity. In
      addition to the monitoring of the self-assembled monolayer (SAM) in real time, we
      report an unprecedented limit of detection (LOD) as low as 2 pM. Finally, an
      immunosensing experiment is realized with human transferrin (dissociation
      constant Kd~10(-8) M(-1)). It allows to assess both the reversibility and the
      robustness of the SPR-TFBG biosensors and to confirm their high sensitivity.

PMID- 23973935
TI  - Proximity-dependent protein detection based on enzyme-assisted fluorescence
      signal amplification.
AB  - In this paper, we develop a sensitive fluorescence method for protein detection
      based on proximity extension and enzyme-assisted signal amplification. In this
      novel method, pairs of proximity probes are designed, and the recognition
      elements are integrated into the proximity probes. Then proteins are detected by
      transforming aptamer or antibody-protein binding signals into DNA detection based
      on proximity effect. In addition, nick sites are introduced into the proximity
      probes to amplify the detectable signal. As proof of concept, detection of human
      alpha-thrombin and human IgG are demonstrated in this study. The aptamers and
      antibodies are coupled in the proximity probes as recognition elements for human
      alpha-thrombin and human IgG respectively. In the presence of target protein,
      aptamer or antibody-protein binding signals are transformed into detectable
      signals by the proximity effect, and can be further amplified by enzyme-assisted
      strand displacement. The above mentioned strategies consequently bring the limit
      of detection (LOD) to as low as 1 pM for human alpha-thrombin and 6 pM for human
      IgG. Furthermore, this method might be extended to sensitive detection of other
      proteins by changing recognition elements of proximity probes.

PMID- 23973936
TI  - Preparation and characterization of bovine serum albumin surface-imprinted
      thermosensitive magnetic polymer microsphere and its application for protein
      recognition.
AB  - A novel bovine serum albumin surface-imprinted thermosensitive magnetic composite
      microsphere was successfully prepared by the surface grafting copolymerization
      method in the presence of temperature-sensitive monomer N-isopropylacrylamide
      (NIPAM), functional monomer methacrylic acid (MAA) and cross-linking agent N,N'
      methylenebisacrylamide (MBA). The structure and component of the thermosensitive
      magnetic molecularly imprinted microsphere were investigated by transmission
      electron microscopy (TEM), Fourier transform infrared (FT-IR), vibrating sample
      magnetometer (VSM) and thermogravimetric analysis (TGA). The results of
      thermosensitivity, adsorption capacity, selectivity and reusability showed the
      formation of a thermosensitivity grafting polymer layer P(NIPAM-MAA-MBA) on the
      surface of Fe3O4@SiO2 and the good adsorption capacity and specific recognition
      for template protein. When the adsorption temperature was higher than the lower
      critical solution temperature (LCST) of poly(N-isopropylacrylamide) (PNIPAM),
      shape memory effect of imprinted cavities would be more effective. In other
      words, it was more conducive to capture template molecules under this condition
      and the imprinting factor would be higher. On the other hand, when the desorption
      temperature was lower than LCST of PNIPAM, the decrease of shape memory effect
      between imprinted cavities and template molecules would facilitate the release of
      template molecules from the imprinted cavities. Based on this property, the
      adsorption and desorption of template molecules could be regulated by system
      temperature indirectly which benefited from the existence of thermosensitivity
      imprinting layer. 

PMID- 23973937
TI  - Defining progression in nonmuscle invasive bladder cancer: it is time for a new,
      standard definition.
AB  - PURPOSE: Despite being one of the most important clinical outcomes in nonmuscle
      invasive bladder cancer, there is currently no standard definition of disease
      progression. Major clinical trials and meta-analyses have used varying
      definitions or have failed to define this end point altogether. A standard
      definition of nonmuscle invasive bladder cancer progression as determined by
      reproducible and reliable procedures is needed. We examine current definitions of
      nonmuscle invasive bladder cancer progression, and propose a new definition that
      will be more clinically useful in determining patient prognosis and comparing
      treatment options. MATERIALS AND METHODS: The IBCG (International Bladder Cancer
      Group) analyzed published clinical trials and meta-analyses that examined
      nonmuscle invasive bladder cancer progression as of December 2012. The
      limitations of the definitions of progression used in these trials were
      considered, as were additional parameters associated with the advancement of
      nonmuscle invasive bladder cancer. RESULTS: The most commonly used definition of
      nonmuscle invasive bladder cancer progression is an increase in stage from
      nonmuscle invasive to muscle invasive disease. Although this definition is
      clinically important, it fails to include other important parameters of advancing
      disease such as progression to lamina propria invasion and increase in grade.
      CONCLUSIONS: The IBCG proposes the definition of nonmuscle invasive bladder
      cancer progression as an increase in T stage from CIS or Ta to T1 (lamina propria
      invasion), development of T2 or greater or lymph node (N+) disease or distant
      metastasis (M1), or an increase in grade from low to high. Investigators should
      consider the use of this new definition to help standardize protocols and improve
      the reporting of progression.

PMID- 23973938
TI  - Nuclear size as estrogen-responsive chromatin quality parameter of mouse
      spermatozoa.
AB  - Recently, we have investigated the endocannabinoid involvement in chromatin
      remodeling events occurring in male spermatids. Indeed, we have demonstrated that
      genetic inactivation of the cannabinoid receptor type 1 (Cnr1) negatively
      influences chromatin remodeling mechanisms, by reducing histone displacement and
      indices of sperm chromatin quality (chromatin condensation and DNA integrity).
      Conversely, Cnr1 knock-out (Cnr1(-/-)) male mice, treated with estrogens,
      replaced histones and rescued chromatin condensation as well as DNA integrity. In
      the present study, by exploiting Cnr1(+/+), Cnr(+/-) and Cnr1(-/-) epididymal
      sperm samples, we show that histone retention directly correlates with low values
      of sperm chromatin quality indices determining sperm nuclear size elongation.
      Moreover, we demonstrate that estrogens, by promoting histone displacement and
      chromatin condensation rescue, are able to efficiently reduce the greater nuclear
      length observed in Cnr1(-/-) sperm. As a consequence of our results, we suggest
      that nucleus length may be used as a morphological parameter useful to screen out
      spermatozoa with low chromatin quality. 

PMID- 23973939
TI  - Sulfite exposure-induced hepatocyte death is not associated with alterations in
      p53 protein expression.
AB  - Although sulfite (SO3(2-)) is commonly used as an antimicrobial agent and
      preservative in foods, medicines and wine, it has also been listed as an
      important risk factor for the initiation and progression of liver diseases due to
      oxidative damage. In general, apoptosis that is induced by oxidative stress is
      triggered by increases in p53 and alterations in Mdm2 and Bcl-2. However, the
      level of involvement of the p53 signaling pathway, which has been shown to be
      upregulated in some animal studies, in hepatocyte death remains unclear. To
      examine the response of the p53 signaling pathway to stimulation with different
      concentrations of sulfite, a time course study of p53, Mdm2, and Bcl-2 expression
      was conducted in an immortalized hepatic cell line, HL-7702. When the HL-7702
      cells were cultured in the presence of Na2SO3, the cell viability was
      significantly decreased after 24h compared to that of the control group (0mmol/L)
      (p<0.05). Meanwhile, aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) levels in the supernatants of HL-7702 cells were
      significantly increased following Na2SO3 administration. Interestingly, the
      expression of p53 and p-p53 (Ser15) remained unchanged. In addition, no obvious
      alterations in Mdm2 and Bcl-2 expression were observed in HL-7702 cells that had
      been stimulated with various concentrations of sulfite. To further investigate
      the detailed mechanism underlying sulfite toxicity, caspase-3, PCNA and RIP1
      expression in HL-7702 cells was studied. The expression levels of caspase-3 and
      PCNA were unchanged, but RIP1 expression was increased significantly after 24h of
      exposure. In light of this evidence, we propose that sulfite is cytotoxic to
      hepatocytes, but this cytotoxicity is not achieved by direct interruption of the
      p53 signaling pathway. In addition, we propose that an alternative necrotic
      process underlies hepatocellular death following sulfite exposure. 

PMID- 23973940
TI  - Pyrosequencing for the rapid and efficient quantification of allele-specific
      expression.
AB  - We have developed a rapid and sensitive quantitative assay for the measurement of
      individual allelic ratios. This assay minimizes time and labor, the need for
      special restriction endonuclease enzymes for polymorphic sites, and avoids
      heteroduplex formation seen with traditional quantitative PCR-based methods. It
      has improved sensitivity compared to other methods and is capable of
      distinguishing 1% differences in allelic expression. This assay, termed
      Pyrosequencing for Imprinted Expression (PIE), involves the use of an intron
      crossing PCR primer to generate the first PCR product. We applied the assay to
      analyze Insulin-like Growth Factor-2 (IGF2) imprinting in both human and mouse
      prostate tissues. 

PMID- 23973942
TI  - Retinoids induce stem cell differentiation via epigenetic changes.
AB  - Vitamin A (all-trans retinol) and its active metabolites, collectively called
      retinoids, exert potent effects on stem cell differentiation and thus, the
      formation of the entire organism, in part via the modulation of the epigenome.
      All-trans retinoic acid (RA), through binding to the retinoic acid receptors
      (RARs), alters interactions of the RARs with various protein components of the
      transcription complex at numerous genes in stem cells, and some of these protein
      components of the transcription complex then either place or remove epigenetic
      marks on histones or on DNA, altering chromatin structure and leading to an exit
      from the self-renewing, pluripotent stem cell state. Different epigenetic
      mechanisms, i.e. first, primarily H3K27me3 marks and then DNA methylation, may be
      employed by embryonic stem cells and other stem cells for control of early vs.
      late stages of cell differentiation. Creating these stable epigenetic changes
      requires the actions of many molecules, including tet1, polycomb protein
      complexes (PRCs), miRNAs, DNA methyltransferases (DNMTs), and telomerase reverse
      transcriptase. A more complete understanding of retinoid-dependent stem cell
      differentiation should reward us with new insights into the failure to maintain a
      differentiated state that is an essential part of neoplastic cell transformation
      and cancer.

PMID- 23973943
TI  - Endogenous progesterone and its cellular binding sites in wheat exposed to
      drought stress.
AB  - Progesterone is a basic hormone that regulates the metabolism in mammals. The
      presence of this compound has also been found in certain plants. It is believed
      that progesterone can regulate growth processes and resistance to stress,
      however, its precise role in plants remains unknown. The research conducted in
      this study was aimed at analyzing the content of endogenous progesterone and its
      cellular binding sites in the leaves of spring wheat exposed to drought. Changes
      were studied in two cultivars of wheat - a cultivar sensitive to drought (Katoda)
      and tolerant cultivar (Monsun). Plants had undergone periodic droughts during the
      seedling stage or in the phase of heading. The occurrence of free progesterone as
      well as its conjugated forms was observed in wheat studied. The amount of
      progesterone ranged from 0.2 to 5.8pmolgFW(-1) and was dependent on the cultivar,
      age of the plants, stage of development and fluctuated as a result of the
      exposure to drought. Cv. Katoda responded to a water deficit by lowering the
      amount of progesterone and cv. Monsun by increasing its level. Progesterone in
      plants grown in limited water conditions occurred primarily in a free form. While
      in the optimal watering conditions, some of its pool was found in the form of
      conjugates. In the spring wheat the occurrence of binding sites for progesterone
      was detected in cell membranes, cytoplasm and nuclei in the range of 10-36fmol/mg
      of protein. The wheat cultivars tested, Monsun and Katoda, differ in their
      concentration of cellular binding sites for progesterone. This number varied in
      the individual fractions during different stages of plant development and due to
      the effect of drought stress. The number of binding sites for progesterone
      located in the membrane fraction of seedlings and flag leaves increased
      significantly under drought in the cv. Katoda (35-46%), but did not change in the
      cv. Monsun. Whereas the number of cytoplasmic progesterone binding sites
      increased during the drought in the cv. Monsun (about 50%), they did not change
      in the cv. Katoda. Changes in the amount of progesterone and its binding sites in
      the cell under the influence of drought were then different depending on whether
      the cultivar was tolerant or sensitive to drought. The possibility of utilizing
      these changes as markers of drought resistance is discussed. The results obtained
      suggest that progesterone is a part of wheat response to stress factors
      (drought). 

PMID- 23973941
TI  - Retinoid signaling in control of progenitor cell differentiation during mouse
      development.
AB  - The vitamin A metabolite retinoic acid (RA) serves as a ligand for nuclear RA
      receptors that control differentiation of progenitor cells important for
      vertebrate development. Genetic studies in mouse embryos deficient for RA
      generating enzymes have been invaluable for deciphering RA function. RA first
      begins to act during early organogenesis when RA generated in trunk mesoderm
      begins to function as a diffusible signal controlling progenitor cell
      differentiation. In neuroectoderm, RA functions as an instructive signal to
      stimulate neuronal differentiation of progenitor cells in the hindbrain and
      spinal cord. RA is not required for early neuronal differentiation of the
      forebrain, but at later stages RA stimulates neuronal differentiation in
      forebrain basal ganglia. RA also acts as a permissive signal for differentiation
      by repressing fibroblast growth factor (FGF) signaling in differentiated cells as
      they emerge from progenitor populations in the caudal progenitor zone and second
      heart field. In addition, RA signaling stimulates differentiation of
      spermatogonial germ cells and induces meiosis in male but not female gonads. A
      more complete understanding of the normal functions of RA signaling during
      development will guide efforts to use RA as a differentiation agent for
      therapeutic purposes. 

PMID- 23973945
TI  - Non-spherical particles for optical trap assisted nanopatterning.
AB  - Optical trap assisted nanopatterning is a laser direct-write technique that uses
      an optically trapped microsphere as a near-field objective. The type of feature
      that one can create with this technique depends on several factors, one of which
      is the shape of the microbead. In this paper, we examine how the geometry of the
      bead affects the focus of the light through a combination of experiments and
      simulations. We realize nanopatterning using non-spherical dielectric particles
      to shape the light-material interaction. We model the resulting nanoscale
      features with a finite difference time domain simulation and obtain very good
      agreement with the experiments. This work opens the way to systematic engineering
      of the microparticle geometry in order to tailor the near-field focus to specific
      nanopatterning applications. 

PMID- 23973944
TI  - A historical overview of bacteriophage therapy as an alternative to antibiotics
      for the treatment of bacterial pathogens.
AB  - The seemingly inexorable spread of antibiotic resistance genes among microbial
      pathogens now threatens the long-term viability of our current antimicrobial
      therapy to treat severe bacterial infections such as sepsis. Antibiotic
      resistance is reaching a crisis situation in some bacterial pathogens where few
      therapeutic alternatives remain and pan-resistant strains are becoming more
      prevalent. Non-antibiotic therapies to treat bacterial infections are now under
      serious consideration and one possible option is the therapeutic use of specific
      phage particles that target bacterial pathogens. Bacteriophage therapy has
      essentially been re-discovered by modern medicine after widespread use of phage
      therapy in the pre-antibiotic era lost favor, at least in Western countries,
      after the introduction of antibiotics. We review the current therapeutic
      rationale and clinical experience with phage therapy as a treatment for invasive
      bacterial infection as novel alternative to antimicrobial chemotherapy. 

PMID- 23973946
TI  - New image processing and noise reduction technology allows reduction of radiation
      exposure in complex electrophysiologic interventions while maintaining optimal
      image quality: a randomized clinical trial.
AB  - BACKGROUND: Despite their carcinogenic potential, X-rays remain indispensable for
      electrophysiologic (EP) procedures. OBJECTIVE: The purpose of this study was to
      evaluate the dose reduction and image quality of a novel X-ray technology using
      advanced image processing and dose reduction technology in an EP laboratory.
      METHODS: In this single-center, randomized, unblinded, parallel controlled trial,
      consecutive patients undergoing catheter ablation for complex arrhythmias were
      eligible. The Philips Allura FD20 system allows switching between the reference
      (Allura Xper) and the novel X-ray imaging technology (Allura Clarity). Primary
      end-point was overall procedural patient dose, expressed in dose area product
      (DAP) and air kerma (AK). Operator dose, procedural success, and necessity to
      switch to higher dose settings were secondary end-points. RESULTS: A total of 136
      patients were randomly assigned to the novel imaging group (n = 68) or the
      reference group (n = 68). Baseline characteristics were similar, except patients
      in the novel imaging group were younger (58 vs 65 years, P < .01). Median DAP and
      AK were 43% and 40% lower in the novel imaging group, respectively (P < .0001). A
      50% operator dose reduction was achieved in the novel imaging group (P < .001).
      Fluoroscopy time, number of exposure frames, and procedure duration were
      equivalent between the two groups, indicating that the image quality was
      similarly adequate in both groups. Procedural success was achieved in 91% of
      patients in both groups; one pericardial tamponade occurred in the novel imaging
      group. CONCLUSION: The novel imaging technology, Allura Clarity, significantly
      reduces patient and operator dose in complex EP procedures while maintaining
      image quality.

PMID- 23973947
TI  - 2D and 3D TEE evaluation of an early reopening of the LARIAT epicardial left
      atrial appendage closure device.

PMID- 23973948
TI  - Atypical complications encountered with epicardial electrophysiological
      procedures.
AB  - BACKGROUND: With the increasing use, complexity, anatomical approaches, and tools
      related to epicardial procedures, complications previously not seen during
      endovascular ablation are now well recognized with epicardial ablation. Whether
      newer approaches and the regional anatomy of the pericardial space contribute to
      unexpected complications after epicardial access (EpiAcc) is presently unknown.
      OBJECTIVE: To characterize underreported, or novel, complications associated with
      percutaneous EpiAcc as part of an electrophysiology procedure. METHODS: We
      retrospectively reviewed percutaneous EpiAcc as part of an ablation procedure
      from January 1, 2004, to December 31, 2011. RESULTS: Of 116 attempts in 107
      patients, 8 atypical ablation complications (no procedural deaths) were noted;
      complications included delayed pericarditis (2 weeks), chronic refractory
      pericarditis, requirement for snaring of broken intrapericardial wire, pleural
      perforation, phrenic nerve injury despite protective strategies, hemoperitoneum,
      and abdominal-pericardial fistula. CONCLUSION: Vigilance both during and after
      EpiAcc is needed to recognize these complications, some of which may be life
      threatening.

PMID- 23973949
TI  - Nonischemic cardiomyopathy substrate and ventricular tachycardia in the setting
      of coronary artery disease.
AB  - BACKGROUND: Patients with coronary artery disease (CAD) may have ventricular
      tachycardia (VT) from a separate nonischemic process. Catheter ablation in these
      patients can be misguided by abnormalities of coronary arteries. OBJECTIVE: To
      identify (1) the prevalence of unanticipated nonischemic VT in patients with
      known CAD presenting with VT and (2) the substrate and VT characteristics of this
      unique subset of patients. METHODS: We examined consecutive patients referred for
      VT catheter ablation who had a history of myocardial infarction and angiography
      documented CAD with presumed ischemic VT. Patients with low-voltage zones and/or
      VT origin inconsistent with CAD distribution were included for further analysis.
      RESULTS: Of 732 patients, 9 (1.2%) (7 men; median age 74 years; ejection fraction
      30%) fulfilled inclusion criteria. Endocardial left ventricular scar inconsistent
      with CAD distribution was found in 8 patients. In 1 patient, only epicardial left
      ventricular scar was found. The distribution of low voltage (<1.5 mV) was
      predominantly around the aortic and mitral valves. Thirty-one VTs were induced in
      8 patients. Most VTs had right bundle branch block (68%); of these VTs, 67% had
      an R/S transition zone later than lead V4 consistent with basal VT origin.
      Epicardial ablation was necessary in 2 patients. During follow-up (30 [25-39]
      months), 7 of 9 patients (78%) were free of recurrent VT. CONCLUSIONS: A small
      but important subgroup of patients with CAD and VT has a nonischemic
      substrate/etiology for VT. The presence of multiple VTs with basal origin
      suggests a potential nonischemic perivalvular substrate and possible need for
      epicardial VT ablation.

PMID- 23973950
TI  - The Canadian experience with Durata and Riata ST Optim defibrillator leads: a
      report from the Canadian Heart Rhythm Society Device Committee.
AB  - BACKGROUND: The St. Jude Medical Riata family of implantable cardioverter
      defibrillator (ICD) leads has demonstrated a high rate of externalized conductors
      and electrical failure. OBJECTIVE: Given similar design elements of Durata to
      Riata, the purpose of this study was to assess the rates of failure of the Riata
      ST Optim and Durata lead families in Canada. METHODS: All Canadian ICD-implanting
      centers were invited to submit follow-up information on all Optim-coated ICD
      leads implanted. Electrical failure was defined as a rapid change in impedance or
      pacing capture threshold leading to lead revision, or oversensing due to noise.
      Externalized conductors were defined as appearance of conductor wires outside the
      lead body. Systematic fluoroscopic screening for externalized conductors was not
      performed. RESULTS: As of December 1, 2012, 15 of 25 centers provided data on
      3981 leads (44% of those sold in Canada during the same timeframe): 3477 Durata
      and 504 Riata ST Optim leads. The most common model numbers were 7122 (1516 leads
      [38%]), 7121 (707 leads [18%]), and 7120 (622 leads [16%]). Mean follow-up
      duration from implant to December 1, 2012, was 4.47 +/- 0.48 years for Riata ST
      Optim leads and 2.00 +/- 1.10 years for Durata leads. The annual rate of lead
      failure was 0.27% per year for Riata ST Optim leads and 0.24% per year for Durata
      leads. No instances of externalized conductors were identified in the failed
      leads. No deaths were attributed to lead failure; however, 2 patients experienced
      inappropriate shocks due to lead failure. CONCLUSION: The overall electrical
      failure rates of the Riata ST Optim and Durata leads appear to be low, and no
      instances of externalized conductors were observed.

PMID- 23973951
TI  - The funny and not-so-funny effects of dronedarone.

PMID- 23973952
TI  - Left atrial appendage closure followed by 6 weeks of antithrombotic therapy: a
      prospective single-center experience.
AB  - BACKGROUND: Currently, 2 different left atrial appendage (LAA) closure systems
      are available for stroke prevention in nonvalvular atrial fibrillation but
      comparative data are lacking. OBJECTIVES: To prospectively compare procedural
      data and patient outcome for 2 contemporary LAA closure systems and to
      investigate an alternative antithrombotic treatment regimen in high-risk
      patients. METHODS: Patients with nonvalvular atrial fibrillation, with high risk
      for stroke, and who either had contraindication or were not willing to accept
      oral anticoagulation were prospectively enrolled. Watchman (Boston Scientific,
      Natick, MA; group A) or Amplatzer Cardiac Plug (St Jude Medical, Minneapolis, MN;
      group B) devices were implanted. All patients received antithrombotic therapy for
      6 weeks. After repeat transesophageal echocardiography, patients were switched to
      aspirin. RESULTS: Eighty patients were enrolled. There was no statistical
      difference in patient characteristics in groups A and B: CHA2DS2VASC score: 4.1
      +/- 1.5 versus 4.5 +/- 1.8; HASBLED score: 3.1 +/- 1.1 versus 3.1 +/- 1.1,
      respectively. LAA closure was achieved in 78 of 80 patients (98%) (group A: 38 of
      40 [95%] vs group B: 40 of 40 [100%]). There was no difference in procedure time
      (group A: 48 +/- 16 minutes vs group B: 47 +/- 15 minutes; P = .69) and
      fluoroscopy time (group A: 6.0 +/- 4.7 minutes vs group B: 7.3 +/- 4.4 minutes; P
      = .25). Major complications included 1 air embolism and delayed tamponade in each
      group. After 6 weeks, 1 device dislodgment and 4 device-related thrombi were
      detected. Ninety-four percent of the patients (73 of 77) were switched to aspirin
      after 6 weeks. During a median follow-up of 364 days (Q1-Q3: 283-539 days), no
      systemic embolism occurred, but 3 patients died (heart failure: n = 2; bleeding:
      n = 1). CONCLUSIONS: Implantation of both LAA closure devices can be performed
      with high success rates in high-risk patients. Postprocedural 6 weeks
      antithrombotic therapy followed by aspirin therapy needs to be confirmed in a
      larger study.

PMID- 23973953
TI  - Familial cardiological and targeted genetic evaluation: low yield in sudden
      unexplained death and high yield in unexplained cardiac arrest syndromes.
AB  - BACKGROUND: It has been reported that cardiological screening and genetic
      evaluation in relatives of families with sudden unexplained death syndrome and
      unexplained cardiac arrest (UCA) may uncover a heritable etiology in a
      significant proportion of families. OBJECTIVE: To evaluate the yield of a
      comprehensive evaluation protocol of a large unselected cohort of consecutive
      families with autopsy-negative sudden unexplained death syndrome (termed sudden
      arrhythmic death syndrome [SADS]) and UCA. METHODS: We studied (1) 109
      consecutive families (411 relatives) referred with 1 or more sudden deaths in the
      family and (2) 52 consecutive probands with UCA (91 relatives) referred by
      cardiologists between January 2007 and December 2012. A comprehensive
      cardiological screening was performed followed by targeted genetic evaluation if
      a clinical phenotype was proven or suspected. Diagnosis was made by a
      multidisciplinary team using published clinical criteria. RESULTS: A diagnosis
      was made in 19 of 109 families with SADS (yield 18%), with the majority having
      long QT syndrome (LQTS). Diagnosis varied according to proband age, with LQTS
      most common in the very young (<=20 years) and Brugada syndrome in the older age
      probands (>=40 years) (P = .03). In contrast, a diagnosis was made in 32 of 52
      families with UCA (yield 62%), the majority of which had LQTS and Brugada
      syndrome. No clinical or circumstantial factors increased the likelihood of
      diagnosis in families with either SADS or UCA. CONCLUSIONS: In contrast to
      previously published series, a comprehensive strategy of cardiological evaluation
      and targeted genetic testing in more than 100 families with SADS was found to
      have a lower diagnostic yield (18%). Diagnostic yield in families with UCA was
      approximately 4 times higher (62%), which is consistent with the published
      literature.

PMID- 23973954
TI  - Impact of the right ventricular lead position on clinical outcome and on the
      incidence of ventricular tachyarrhythmias in patients with CRT-D.
AB  - BACKGROUND: Data on the impact of right ventricular (RV) lead location on
      clinical outcome and ventricular tachyarrhythmias in cardiac resynchronization
      therapy with defibrillator (CRT-D) patients are limited. OBJECTIVE: To evaluate
      the impact of different RV lead locations on clinical outcome in CRT-D patients
      enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac
      Resynchronization Therapy trial. METHODS: We investigated 742 of 1089 CRT-D
      patients (68%) with adjudicated RV lead location enrolled in the Multicenter
      Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy
      trial to evaluate the impact of RV lead location on cardiac events. The primary
      end point was heart failure or death; secondary end points included ventricular
      tachycardia (VT), ventricular fibrillation (VF), or death and VT or VF alone.
      RESULTS: Eighty-six patients had the RV lead positioned at the RV septal or right
      ventricular outflow tract region, combined as nonapical RV group, and 656
      patients had apical RV lead location. There was no difference in the primary end
      point in patients with nonapical RV lead location versus those with apical RV
      lead location (hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.54-1.80; P
      = .983). Echocardiographic response to CRT-D was comparable across RV lead
      location groups (P > .05 for left ventricular end-diastolic volume, left
      ventricular end-systolic volume, and left atrial volume percent change). However,
      nonapical RV lead location was associated with significantly higher risk of
      VT/VF/death (HR 2.45; 95% CI 1.36-4.41; P = .003) and VT/VF alone (HR 2.52; 95%
      CI 1.36-4.65; P = .002), predominantly in the first year after device
      implantation. Results were consistent in patients with left bundle branch block.
      CONCLUSIONS: In CRT-D patients, there is no benefit of nonapical RV lead location
      in clinical outcome or echocardiographic response. Moreover, nonapical RV lead
      location is associated with an increased risk of ventricular tachyarrhythmias,
      particularly in the first year after device implantation.

PMID- 23973955
TI  - Sexual dimorphism in fat distribution and metabolic profile in mice offspring
      from diet-induced obese mothers.
AB  - AIMS: To investigate whether the effects of diet-induced obesity in mothers are
      passed on to their offspring fed a control diet in a gender-specific manner. MAIN
      METHODS: Mother mice received either standard chow (SC; 17% energy from fat) or
      high-fat (HF; 49% energy from fat) diet for eight weeks pre-pregnancy until
      lactation. After weaning (at 21 days of age), offspring received SC diet and were
      divided into four groups according to the mother's diet (Mo): male Mo-SC, female
      Mo-SC, male Mo-HF, and female Mo-HF. Stereology, Elisa and western blotting were
      performed. KEY FINDINGS: HF diet-fed mothers were overweight, and had metabolic
      abnormalities, all of which were found in their adult offspring. Male Mo-HF
      offspring had higher cholesterol, triglycerides, leptin and insulin levels and
      lower circulating adiponectin than female Mo-HF offspring. Mo-HF offspring of
      both genders had higher expression of tumor necrosis factor-alpha, interleukin-6
      and leptin and lower expression of adiponectin than Mo-SC offspring; however,
      male Mo-HF were more affected than female Mo-HF offspring for these variables,
      demonstrating sexual dimorphism. SIGNIFICANCE: Exposure to HF diet is effective
      in inducing obesity and metabolic alterations in mothers, and this phenotype can
      be passed on to their offspring. An adverse pattern in the body fat distribution
      in males probably has favored the intensification of a pro-inflammatory profile
      compared with females. In adulthood, the male offspring responds to the maternal
      obesity more than the female offspring, indicating a relevant sexual dimorphism
      that is a novel finding in this animal study.

PMID- 23973956
TI  - Antipsychotics promote the differentiation of oligodendrocyte progenitor cells by
      regulating oligodendrocyte lineage transcription factors 1 and 2.
AB  - AIMS: Oligodendrocyte/myelin abnormalities may be an important component of the
      pathogenesis found in schizophrenia. The aim of this current study was to examine
      the possible effects of the antipsychotic drugs (APDs) haloperidol (HAL),
      olanzapine (OLA), and quetiapine (QUE) on the development of oligodendroglial
      lineage cells. MAIN METHODS: CG4 cells, an oligodendrocyte progenitor cell line,
      were treated with various concentrations of HAL, OLA, or QUE for specific
      periods. The proliferation and differentiation of the CG4 cells were measured.
      The regulation of CG4 cell differentiation by oligodendrocyte lineage
      transcription factors 1 and 2 (Olig1 and Olig2) was examined. KEY FINDINGS: The
      APDs used in this study had no effect on the proliferation of CG4 cells. The APDs
      elevated the expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), a
      specific marker of oligodendrocytes, and promoted the CG4 cells to differentiate
      into CNP positive oligodendrocytes. QUE and OLA increased the expression of both
      Olig1 and Olig2 whereas HAL only increased the expression of Olig2. SIGNIFICANCE:
      Our findings suggest that oligodendrocyte development is a target of HAL, OLA,
      and QUE and provide further evidence of the important role of oligodendrocytes in
      the pathophysiology and treatment of schizophrenia. They also indicate that the
      expression level of oligodendrocyte/myelin-related genes could be profoundly
      affected by APDs, which should be considered in future studies aiming to measure
      the oligodendrocyte/myelin-related gene expressions in schizophrenia patients.

PMID- 23973957
TI  - Developing principles of sustainability and stakeholder engagement for "gentle"
      remediation approaches: the European context.
AB  - Gentle Remediation Options (GRO) are risk management strategies or techniques for
      contaminated sites that result in no gross reduction in soil functionality (or a
      net gain) as well as risk management. Intelligently applied GROs can provide: (a)
      rapid risk management via pathway control, through containment and stabilisation,
      coupled with a longer term removal or immobilisation/isolation of the contaminant
      source term; and (b) a range of additional economic (e.g. biomass generation),
      social (e.g. leisure and recreation) and environmental (e.g. CO2 sequestration)
      benefits. In order for these benefits to be optimised or indeed realised,
      effective stakeholder engagement is required. This paper reviews current sector
      practice in stakeholder engagement and its importance when implementing GRO and
      other remediation options. From this, knowledge gaps are identified, and
      strategies to promote more effective stakeholder engagement during GRO
      application are outlined. Further work is required on integrating stakeholder
      engagement strategies into decision support systems and tools for GRO (to raise
      the profile of the benefits of effective stakeholder engagement and
      participation, particularly with sector professionals), and developing criteria
      for the identification of different stakeholder profiles/categories. Demonstrator
      sites can make a significant contribution to stakeholder engagement via providing
      evidence on the effectiveness of GRO under varying site contexts and conditions.
      Effective and sustained engagement strategies however will be required to ensure
      that site risk is effectively managed over the longer-term, and that full
      potential benefits of GRO (e.g. CO2 sequestration, economic returns from biomass
      generation and "leverage" of marginal land, amenity and educational value,
      ecosystem services) are realised and communicated to stakeholders. 

PMID- 23973959
TI  - The Coprinopsis cinerea septin Cc.Cdc3 is involved in stipe cell elongation.
AB  - We have identified and characterized a Coprinopsis cinerea mutant defective in
      stipe elongation during fruiting body development. In the wild-type, stipe cells
      elongate at the maturation stage of fruiting, resulting in very slender cells. In
      the mutant, the stipe cells fail to elongate, but become rather globular at the
      maturation stage. We found that the mutant phenotype is rescued by a gene
      encoding a homolog of Saccharomyces cerevisiae CDC3 septin, Cc.Cdc3. The C.
      cinerea genome includes 6 septin genes, 5 of which, including Cc.cdc3, are highly
      transcribed during stipe elongation in the wild type. In the mutant, the level of
      Cc.cdc3 transcription in the stipe cells remains the same as that in the
      mycelium, and the level of Cc.cdc10 transcription is approximately 100 times
      lower than that in the wild-type stipe cells. No increase in transcription of
      Cc.cdc3 in the mutant may be due to the fact that the Cc.cdc3 gene has a 4-base
      pair insertion in its promoter and/or that the promoter region is methylated in
      the mutant. Overexpressed EGFP-Cc.Cdc3 fusion protein rescues the stipe
      elongation in the transformants, localizes to the cell cortex and assembles into
      abundant thin filaments in the elongating stipe cells. In contrast, in vegetative
      hyphae, EGFP-Cc.Cdc3 is localized to the hyphal tips of the apical cells of
      hyphae. Cellular defects in the mutant, combined with the localization of EGFP
      Cc.Cdc3, suggest that septin filaments in the cell cortex provide the localized
      rigidity to the plasma membrane and allow cells to elongate cylindrically. 

PMID- 23973960
TI  - In praise of erroneous hypotheses.
AB  - In the sixties Cove and Pateman discovered that mutants of Aspergillus nidulans
      lacking nitrate reductase activity were constitutive for the expression of genes
      induced by nitrate and dependent on the transcription factor NirA. They proposed
      that the nitrate protein acted as a repressor, preventing the transcription
      factor activity of NirA. Nitrate-mediated regulation behaved similarly in other
      organisms. This "autogenous regulation hypothesis" has recently shown to be
      erroneous, in the very organism for which it was first proposed. Nevertheless
      this erroneous hypothesis have led to a thorough dissection of the process of
      regulation of nitrate assimilation and more importantly to a hypothesis bearing
      on the origin of metabolite-responsive transcription factors. In this article I
      discuss the heuristic value and evolutionary importance of autogenous regulation.

PMID- 23973962
TI  - Invited commentary.

PMID- 23973961
TI  - The p53-Mdm2 feedback loop protects against DNA damage by inhibiting p53 activity
      but is dispensable for p53 stability, development, and longevity.
AB  - The p53-Mdm2 feedback loop is perceived to be critical for regulating stress
      induced p53 activity and levels. However, this has never been tested in vivo.
      Using a genetically engineered mouse with mutated p53 response elements in the
      Mdm2 P2 promoter, we show that feedback loop-deficient Mdm2(P2/P2) mice are
      viable and aphenotypic and age normally. p53 degradation kinetics after DNA
      damage in radiosensitive tissues remains similar to wild-type controls.
      Nonetheless, DNA damage response is elevated in Mdm2(P2/P2) mice. Enhanced p53
      dependent apoptosis sensitizes hematopoietic stem cells (HSCs), causing drastic
      myeloablation and lethality. These results suggest that while basal Mdm2 levels
      are sufficient to regulate p53 in most tissues under homeostatic conditions, the
      p53-Mdm2 feedback loop is critical for regulating p53 activity and sustaining HSC
      function after DNA damage. Therefore, transient disruption of p53-Mdm2
      interaction could be explored as a potential adjuvant/therapeutic strategy for
      targeting stem cells in hematological malignancies.

PMID- 23973963
TI  - In response.

PMID- 23973964
TI  - In response.

PMID- 23973965
TI  - Characterization and genomic analysis of two Staphylococcus aureus bacteriophages
      isolated from poultry/livestock farms.
AB  - Staphylococcus aureus is one of the most important pathogens, causing various
      diseases in humans and animals. As methicillin-resistant S. aureus (MRSA) has
      become increasingly prevalent, controlling this pathogen with standard antibiotic
      treatment has become challenging. Bacteriophages (phages) have attracted interest
      as alternative antibacterial agents to control MRSA. In this study, we isolated
      six S. aureus phages from soils of poultry/livestock farms. Based on the results
      of host range determination with 150 S. aureus strains and restriction enzyme
      treatment of phage DNA, two phages, designated SP5 and SP6, were selected for
      further characterization and genome sequencing. Both SP5 and SP6 were classified
      as members of the family Siphoviridae. The genome of SP5 comprises 43 305 bp and
      contains 63 ORFs, while the SP6 genome comprises 42 902 bp and contains 61 ORFs.
      Although they have different host spectra, the phage genomes exhibit high
      nucleotide similarity to each other. Adsorption assay results suggested that the
      host range determinants of the two phages are involved in both adsorption and
      infection. Comparative genomic analyses of the two phages provided evidence that
      the lysogenic/lytic control module and tail proteins may be important for host
      specificity.

PMID- 23973966
TI  - Genome-wide search and comparative genomic analysis of the trypsin inhibitor-like
      cysteine-rich domain-containing peptides.
AB  - It was shown that peptides containing trypsin inhibitor-like cysteine-rich (TIL)
      domain are able to inhibit proteinase activities, and thus play important roles
      in various biological processes, such as immune response and anticoagulation.
      However, only a limited number of the TIL peptides have been identified and
      characterized so far; and little has been known about the evolutionary
      relationships of the genes encoding the TIL peptides. BmKAPi is a TIL domain
      containing peptide that was identified from Mesobuthus martensii Karsch. Here, we
      conducted genome-wide searches for new peptides that are homologous to BmKAPi or
      possess a cysteine pattern similar to that of BmKAPi. As a result, we identified
      a total of 80 different TIL peptides from 34 species of arthropods. We found that
      these peptides can be classified into seven evolutionarily distinct groups.
      Furthermore, we cloned the genomic sequence of BmKAPi; the genomic sequences of
      the majority of other TIL peptides were also identified from the GenBank database
      using bioinformatical approaches. Through phylogenetic and comparative genomic
      analysis, we found 26 cases of intron gain events occurred in the genes of the
      TIL peptides; however, no instances of intron loss were observed. Moreover, we
      found that alternative splicing contributes to the diversification of the TIL
      peptides. It is interesting to see that four genes of the TIL domain-containing
      peptides overlap in a DNA region located on the chromosome LG B15 of Bombus
      terretris. These data suggest that the evolution of the TIL peptide genes are
      dynamic, which was dominated by intron gain. 

PMID- 23973967
TI  - NMR solution structure and SRP54M predicted interaction of the N-terminal
      sequence (1-30) of the ovine Doppel protein.
AB  - Prion protein (PrP(C)) biosynthesis involves a multi-step process that includes
      translation and post-translational modifications. While PrP has been widely
      investigated, for the homolog Doppel (Dpl), limited knowledge is available. In
      this study, we focused on a vital step of eukaryotic protein biosynthesis:
      targeting by the signal recognition particle (SRP). Taking the ovine Dpl (OvDpl(1
      30)) peptide as a template, we studied its behavior in two different hydrophobic
      environments using CD and NMR spectroscopy. In both trifluoroethanol (TFE) and
      dihexanoyl-sn-glycero-3-phosphatidylcholine (DHPC), the OvDpl(1-30) peptide
      revealed to fold in an alpha-helical conformation with a well-defined central
      region extending from residue Cys8 until Ser22. The NMR structure was
      subsequently included in a computational docking complex with the conserved M
      domain of SRP54 protein (SRP54M), and further compared with the N-terminal
      structures of mouse Dpl and bovine PrP(C) proteins. This allowed the
      determination of (i) common predicted N-terminal/SRP54M polar contacts (Asp331,
      Gln335, Glu365 and Lys432) and (ii) different N-C orientations between prion and
      Dpl peptides at the SRP54M hydrophobic groove, that are in agreement with each
      peptide electrostatic potential. Together, these findings provide new insights
      into the biosynthesis of prion-like proteins. Besides they also show the role of
      protein conformational switches in signalization toward the endoplasmic membrane,
      a key event of major significance in the cell cycle. They are thus of general
      applicability to the study of the biological function of prion-like as well as
      other proteins. 

PMID- 23973968
TI  - Sulfonated modification of cotton linter and its application as adsorbent for
      high-efficiency removal of lead(II) in effluent.
AB  - Sulfonated modification of cotton linter and its novel application as adsorbent
      for Pb(2+) in effluent were investigated. Results show that sulfonated cotton
      linter (SCL) has strong adsorbability for Pb(2+), more than 85% of Pb(2+) can be
      removed at lower Pb(2+) concentration (<20 mg/L). Its adsorbability for Pb(2+) is
      related to effluent pH, temperature, and initial Pb(2+) concentration. The
      adsorption process can reach equilibrium within 8 min, which can be described
      through the pseudo-second-order kinetic model. The adsorption isotherm is closely
      fitted with the Temkin isotherm model, which suggests that the adsorption of
      Pb(2+) on SCL can be regarded as chemical adsorption. The adsorption process of
      Pb(2+) on SCL is non-spontaneous and endothermic, based on the value of Gibbs
      free energy and enthalpy. Compared with commercial activated carbon, SCL is
      simple to prepare and does not require any special technology.

PMID- 23973969
TI  - Removal of Ni (II) ions from aqueous solutions using modified rice straw in a
      fixed bed column.
AB  - This paper investigates the ability of modified rice straw, an agricultural
      biomaterial, to remove Ni (II) ions from aqueous solution in a fixed-bed column.
      The experiments were performed with different bed heights (1.5 and 2.0 cm),
      influent Ni (II) concentrations (50, 75 and 100 mg/L) using flow rates (500
      MUl/min) in order to obtain experimental breakthrough curves. The maximum
      adsorption capacity of rice straw powder (RSP) was 43 mg/L at 75 mg/L influent
      concentration of divalent Ni (II) ions at 2 cm bed depth. Adams-Bohart model,
      Thomas model and Yoon and Nelson kinetic models were used to analyze the column
      performance. The value of rate constant for Adams-Bohart and Yoon and Nelson
      model decreased with increase of influent concentration, but increased with
      increasing bed depth. The rate constant for Thomas model increased with initial
      influent Ni (II) ions concentration, decreased with increase in bed depth.

PMID- 23973970
TI  - How to ascertain the importance of autotrophic denitrification process in a
      bioelectrochemical system.
AB  - The ratio of autotrophic denitrification (Rauto) is proposed as a metric to
      better evaluate the nitrate removal efficiency of bioelectrochemical systems
      (BESs). Two methods for computing Rauto were compared, one based on electron
      charge transfer and the other on a controlled reaction. The experiment was
      conducted in a greenhouse with a temperature of 30+/-2  degrees C. A reaction
      with a constant voltage supply was used as a BES and open circuit control was
      used for the controlled reaction. The results indicated that calculating the
      Rauto based on electron charge transfer was more suitable for evaluating the
      performance of BESs. Further discussion about the factors influencing the result
      of this computing method is presented.

PMID- 23973971
TI  - Ammonium recovery from reject water combined with hydrogen production in a
      bioelectrochemical reactor.
AB  - In this study, a bioelectrochemical reactor was investigated for simultaneous
      hydrogen production and ammonium recovery from reject water, which is an ammonium
      rich side-stream produced from sludge treatment processes at wastewater treatment
      plants. In the anode chamber of the reactor, microorganisms converted organic
      material into electrical current. The electrical current was used to generate
      hydrogen gas at the cathode with 96+/-6% efficiency. Real or synthetic reject
      water was fed to the cathode chamber where proton reduction into hydrogen gas
      resulted in a pH increase which led to ammonium being converted into volatile
      ammonia. The ammonia could be stripped from the solution and recovered in acid.
      Overall, ammonium recovery efficiencies reached 94% with synthetic reject water
      and 79% with real reject water. This process could potentially be used to make
      wastewater treatment plants more resource-efficient and further research is
      warranted. 

PMID- 23973972
TI  - Use of low frequency and density ultrasound to stimulate partial nitrification
      and simultaneous nitrification and denitrification.
AB  - Low frequency and density ultrasound has attracted considerable attention in
      enhancing wastewater treatment performance, particularly in the removal of
      nitrogen. In the present study, two sequencing batch reactors were operated to
      confirm the effects of ultrasound at the frequency of 40 kHz and density of 0.027
      W/mL on partial nitrification and simultaneous nitrification and denitrification
      (SND). At the optimal irradiation time of 2.0 h, the obtained nitrite
      accumulation ratio and SND efficiency at full aerobic were 73.9% and 72.8%,
      respectively. Nitrite accumulation was the result of increased NH4(+)-N removal
      and improved ammonia oxidizing bacteria (AOB) activity with simultaneous
      inhibition of nitrite oxidizing bacteria (NOB) activity. Ultrasonic treatment
      could provide suitable conditions in temperature and pH for AOB growth, and
      destroy the NOB community structure. Moreover, organic matters were released and
      offered an additional carbon source for denitrification apart from the negative
      effects on sludge properties.

PMID- 23973973
TI  - High-level extracellular production of alkaline polygalacturonate lyase in
      Bacillus subtilis with optimized regulatory elements.
AB  - The present work aims to construct a robust recombinant Bacillus subtilis to
      achieve secretory production of alkaline polygalacturonate lyase (PGL). First, 6
      signal peptides (amyX, bpr, vpr, yvgO, wapA and nprE) were screened with a semi
      rational approach and comparatively investigated their effects on the production
      of PGL. The signal peptide bpr directed efficient PGL secretory expression and
      increased PGL titer to 313.7 U mL(-1). By optimizing and applying strong promoter
      P43 and Shine-Dalgarno sequence, higher titer of 446.3 U mL(-1) PGL was achieved.
      Finally, the capacity of the recombinant B. subtilis WB43CB was evaluated with a
      fed-batch strategy in 3 L fermentor. The PGL titer reached 632.6 U mL(-1) with a
      productivity of 17.6 U mL(-1) h(-1), which was the highest secretory production
      of PGL by the B. subtilis system. The recombinant B. subtilis strain WB43CB
      constructed in the present work has great potential in production of alkaline
      PGL.

PMID- 23973975
TI  - Effects of organic loading rate and effluent recirculation on the performance of
      two-stage anaerobic digestion of vegetable waste.
AB  - The effects of organic loading rates (OLR) and effluent recirculation on dynamics
      of acidogenic and methanogenic processes in two-stage anaerobic digestion of
      vegetable waste were investigated. Two systems were performed at OLRs of 1.3,
      1.7, 2.1 and 2.6 g VS/L/d. One system recirculated the effluent from the
      methanogenic reactor to acidogenic reactor. With increasing OLRs, total volatile
      fatty acid (VFA) concentration increased to approximately 8500 mg/L in acidogenic
      digester, where pH decreased from 6.4 to 5.2. Daily biogas production and methane
      content in methanogenic reactor increased from 1.2 to 4.4 L/d and from 27.4% to
      60.5%, respectively. However, inhibition of hydrolysis in acidogenic reactor was
      demonstrated under the OLR of 2.6 g VS/L/d without recirculation, thus indicating
      system overloading. Effluent recirculation shown a considerable positive effect
      on alleviating VFA inhibition and improving biogas production in acidogenic
      reactor because of the effect of dilution and pH adjustment, particularly at high
      OLRs.

PMID- 23973974
TI  - Novel method utilizing microbial treatment for cleaner production of diosgenin
      from Dioscorea zingiberensis C.H. Wright (DZW).
AB  - A novel method utilizing microbial treatment for cleaner production of diosgenin
      from Dioscorea zingiberensis C.H. Wright (DZW) was presented. A new Bacillus
      pumilus HR19, which has the great ability to secrete pectinase, was screened and
      applied in the microbial treatment. Low-pressure steam expansion pretreatment
      (LSEP) was employed in advance to assist microbial treatment efficiently in
      releasing saponins, which are the precursors of diosgenin. Compared with the
      traditional process of acid hydrolysis, this novel process reduced the
      consumptions of water, acid and organic solvent by more than 92.5%, 97.0%, 97.0%,
      respectively, while simultaneously increasing the diosgenin yield by 6.21%. In
      addition, the microbial treatment was more efficient than enzymatic treatment,
      which arised from that microorganisms could be induced to secrete related enzymes
      by the compositions of DZW and relieve product inhibition by utilizing enzyme
      hydrolysates.

PMID- 23973976
TI  - The combined effect of bacteria and Chlorella vulgaris on the treatment of
      municipal wastewaters.
AB  - Impacts of Chlorella vulgaris with or without co-existing bacteria on the removal
      of nitrogen, phosphorus and organic matter from wastewaters were studied by
      comparing the wastewater treatment effects between an algae-bacteria consortium
      and a stand-alone algae system. In the algae-bacteria system, C.vulgaris played a
      dominant role in the removal of nitrogen and phosphorus, while bacteria removed
      most of the organic matter from the wastewater. When treating unsterilized
      wastewater, bacteria were found to inhibit the growth of algae at >231 mg/L
      dissolved organic carbon (DOC). Using the algae-bacteria consortium resulted in
      the removal of 97% NH4(+), 98% phosphorus and 26% DOC at a total nitrogen (TN)
      level of 29-174 mg/L. The reaction rate constant (k) values in sterilized and
      unsterilized wastewaters were 2.17 and 1.92 mg NH4(+)-N/(mg algal cell .d),
      respectively.

PMID- 23973977
TI  - Production of aviation fuel via catalytic hydrothermal decarboxylation of fatty
      acids in microalgae oil.
AB  - A series of fatty acids in microalgae oil, such as stearic acid, palmitic acid,
      lauric acid, myristic acid, arachidic acid and behenic acid, were selected as the
      raw materials to produce aviation fuel via hydrothermal decarboxylation over a
      multi-wall carbon nanotube supported Pt catalyst (Pt/MWCNTs). It was found that
      Pt/MWCNTs catalysts exhibited higher activity for the hydrothermal
      decarboxylation of stearic acid with a 97% selectivity toward heptadecane
      compared to Pt/C and Ru/C under the same conditions. And Pt/MWCNTs is also
      capable for the decarboxylation of different fatty acids in microalgae oil. The
      reaction conditions, such as Pt/MWCNTs loading amount, reaction temperature and
      time were optimized. The activation energy of stearic acid decarboxylation over
      Pt/MWCNTs was calculated (114 kJ/mol).

PMID- 23973978
TI  - Tracking organic matter and microbiota dynamics during the stages of
      lignocellulosic waste composting.
AB  - The dynamics of biologically meaningful soluble and polymeric carbon fractions
      and the combined relationships between physical, chemical and biological
      parameters during composting of lignocellulosic waste were evaluated. The first
      thermophilic stage is crucial in determining the further evolution of soluble and
      polymeric carbon fractions but the dynamics of carbon is still important at the
      maturation stage. Multivariate data analysis showed that not only are all
      parameters interrelated but also influence one another's variability. To discern
      completion of bio-oxidative stage other parameters in addition to temperature
      should be measured. Evaluation of soluble organic carbon, microbial biomass
      carbon, pH and inorganic nitrogen can be of great use in detecting the composting
      stage. This study offers new insights into the mechanisms involved in the
      biodegradation of organic matter and help to prioritize the parameters that
      contribute at critical stages of the process.

PMID- 23973979
TI  - The influence of thermochemical treatments on the lignocellulosic structure of
      wheat straw as studied by natural abundance 13C NMR.
AB  - The effects of thermochemical treatments (aquathermolysis, pyrolysis, and
      combinations thereof) on the lignocellulosic structure and composition of wheat
      straw were studied with (13)C and (1)H solid state NMR spectroscopy and proton
      T1rho relaxation measurements. Results show that aquathermolysis removes
      hemicellulose, acetyl groups, and ash minerals. As a result, the susceptibility
      of lignocellulose to pyrolysis is reduced most likely due to the removal of
      catalytically active salts, although recondensation of lignin during
      aquathermolysis treatment can also play a role. In contrast to pyrolysis of wheat
      straw, pyrolysis of aquathermolysed wheat straw leaves traces of cellulose in the
      char as well as more intense lignin methoxy peaks. Finally, it was found that
      both pyrolysis chars contain aliphatic chains, which were attributed to the
      presence of cutin or cutin-like materials, a macromolecule that covers the aerial
      surface of plants, not soluble in water and seemingly stable under the pyrolysis
      conditions applied.

PMID- 23973980
TI  - The enhancement of completely autotrophic nitrogen removal over nitrite (CANON)
      by N2H4 addition.
AB  - The long-term addition of N2H4 to completely autotrophic nitrogen removal over
      nitrite (CANON) sequencing batch reactors (SBRs) recovered and enhanced their
      autotrophic nitrogen removal capacity while simultaneously reducing their
      production of NO3(-). The total nitrogen (TN) removal rate and TN removal
      efficiency of the process increased from 0.202+/-0.011 to 0.370+/-0.016 kg
      N/m(3)/d and from 65.1+/-3.75% to 77.4+/-3.8%, respectively, and the molar ratio
      of NO3(-) production to NH4(+) removal (MRNN) decreased to 0.058. The most
      effective concentration of N2H4 addition was approximately 3.99 mg/L. N2H4 could
      increase the specific growth rate of anaerobic ammonium-oxidizing bacteria
      (AnAOB) and inhibit aerobic ammonia oxidation. The electrons released from the
      oxidation of additional N2H4 using hydrazine dehydrogenase (HDH), which
      substituted the electrons from NO2(-) oxidation to NO3(-), replenished the
      consumption of AnAOB anabolism and significantly reduced the consequent NO3(-)
      production.

PMID- 23973981
TI  - Increased production of cellulases and xylanases by Penicillium echinulatum S1M29
      in batch and fed-batch culture.
AB  - The development of more productive strains of microorganisms and processes that
      increase enzyme levels can contribute to the economically efficient production of
      second generation ethanol. To this end, cellulases and xylanases were produced
      with the S1M29 mutant strain of Penicillium echinulatum, using different
      concentrations of cellulose (20, 40, and 60 g L(-1)) in batch and fed-batch
      processes. The highest activities of FPase (8.3 U mL(-1)), endoglucanases (37.3 U
      mL(-1)), and xylanases (177 U mL(-1)) were obtained in fed-batch cultivation with
      40 g L(-1) of cellulose. The P. echinulatum enzymatic broth and the commercial
      enzyme Cellic CTec2 were tested for hydrolysis of pretreated sugar cane bagasse.
      Maximum concentrations of glucose and xylose were achieved after 72 h of
      hydrolysis. Glucose yields of 28.0% and 27.0% were obtained using the P.
      echinulatum enzymatic extract and Cellic CTec2, respectively.

PMID- 23973982
TI  - Biological abatement of cellulase inhibitors.
AB  - Removal of enzyme inhibitors released during lignocellulose pretreatment is
      essential for economically feasible biofuel production. We tested bio-abatement
      to mitigate enzyme inhibitor effects observed in corn stover liquors after
      pretreatment with either dilute acid or liquid hot water at 10% (w/v) solids. Bio
      abatement of liquors was followed by enzymatic hydrolysis of cellulose. To
      distinguish between inhibitor effects on enzymes and recalcitrance of the
      substrate, pretreated corn stover solids were removed and replaced with 1% (w/v)
      Solka Floc. Cellulose conversion in the presence of bio-abated liquors from
      dilute acid pretreatment was 8.6% (0.1x enzyme) and 16% (1x enzyme) higher than
      control (non-abated) samples. In the presence of bio-abated liquor from liquid
      hot water pretreated corn stover, 10% (0.1x enzyme) and 13% (1x enzyme) higher
      cellulose conversion was obtained compared to control. Bio-abatement yielded
      improved enzyme hydrolysis in the same range as that obtained using a chemical
      (overliming) method for mitigating inhibitors. 

PMID- 23973983
TI  - The thermal behaviour of the co-combustion between paper sludge and rice straw.
AB  - The thermal characteristics and kinetics of paper sludge, rice straw and their
      blends were evaluated under combustion condition. The paper sludge was blended
      with rice straw in the range of 10-95 wt.% to investigate their co-combustion
      behaviour. There was significant interaction between rice straw and paper sludge
      in high temperature. The combustion of paper sludge and rice straw could be
      divided into two stages. The value of the activation energy obtained by the
      Friedman and the Ozawa-Flynn-Wall (OFW) first decreased and then increased with
      the conversion degree rising. The average activation energy did not monotonically
      decrease with increasing the percentage of rice straw in the blends. When the
      percentage of rice straw in the blends was 80%, the value of the average
      activation energy was the smallest, which was 139 kJ/mol obtained by OFW and 132
      kJ/mol obtained by Friedman, respectively.

PMID- 23973984
TI  - Establishment of a new murine model of liver abscess induced by Fusobacterium
      necrophorum injected into the caudal vein.
AB  - Anaerobic bacterial infection is often accompanied by abscess formation; however,
      few in vivo studies have been published with descriptive data specifically
      evaluating antimicrobial activity in the presence of abscesses. The aim of this
      study was to establish a murine model of anaerobic infection with abscess
      formation and to verify the utility of this model for evaluating the in vivo
      efficacy of an antimicrobial agent. A clinical isolate of Fusobacterium
      necrophorum was inoculated into the caudal vein of immunocompetent BALB/c mice at
      10(8) c.f.u. per mouse. Changes in body weight, bacterial load and histopathology
      of key organs were evaluated. After inoculation, bacterial counts in the liver
      increased from 10(4) to 10(8) c.f.u. after 1-3 days, and liver abscess formation
      was observed on the day following infection. Abscess formation and bacterial
      growth were not observed in other organs. In this model, 3 days of treatment with
      5 mg metronidazole kg(-1) eradicated F. necrophorum in the liver; however, a
      reduction in bacterial load was not observed with 0.05 mg metronidazole kg(-1).
      In this study, we established a novel murine model of F. necrophorum liver
      abscess via haematogenous infection that may be useful for investigating in vivo
      antimicrobial activity against anaerobic abscesses and understanding the
      pathogenesis of F. necrophorum infection. 

PMID- 23973985
TI  - Endocarditis due to a co-infection of Candida albicans and Candida tropicalis in
      a drug abuser.
AB  - In recent decades the incidence of Candida endocarditis has increased
      dramatically. Despite the application of surgery and antifungal therapy, Candida
      endocarditis remains a life-threatening infection with significant morbidity and
      mortality. We report a 37-year-old male drug abuser presenting with high fever,
      chest pain, loss of appetite and cardiac failure. His echocardiography revealed
      mobile large tricuspid valve vegetations. Fungal endocarditis was confirmed by
      culturing of the resected vegetation showing mixed growth of Candida albicans and
      Candida tropicalis, although three consecutive blood cultures were negative for
      Candida species. Phenotypic identification was reconfirmed by sequencing of the
      internal transcribed spacer (ITS rDNA) region. The patient was initially treated
      with intravenous fluconazole (6 mg kg(-1) per day), followed by 2 weeks of
      intravenous amphotericin B deoxycholate (1 mg kg(-1) per day). Although MICs were
      low for both drugs, the patient's antifungal therapy combined with valve
      replacement failed, and he died due to respiratory failure. 

PMID- 23973986
TI  - Clinical features and molecular epidemiology of extended-spectrum beta-lactamase
      producing Enterobacteriaceae: the hidden messages.

PMID- 23973987
TI  - Enhancement of Cunninghamella elegans UCP/WFCC 0542 biomass and chitosan with
      amino acid supply.
AB  - Studies were carried out with Cunninghamella elegans UCP/WFCC 0542 to evaluate
      the effects of an abundant supply of amino acids, asparagine and corn steep
      liquor associated with sucrose on the production of biomass and chitosan by
      submerged fermentation. The concentrations of the components of the culture
      medium which were determined by a 23 full factorial design evaluated the
      interactions and effects of the independent variables of the sucrose, asparagine
      and corn steep liquor in relation to carbon and nitrogen sources, on the
      production of chitosan regarding biomass. The best results were observed at the
      central point [asparagine 0.025%, sucrose 0.15% and 0.45% of corn steep liquor,
      ratio C:N=2:6], and produced maximum yields of 16.95 g/L biomass and 2.14 g/L
      chitosan, after 96 h of submerged fermentation. However, the lowest level of
      sucrose, asparagine and corn steep liquor produced a low amount of biomass (10.83
      g/L) and chitosan (0.60 g/L). The infrared spectrum absorption of the chitosan
      produced by C. elegans showed bands regarding OH-axial stretching between 3406
      and 3432 cm-1, superimposed on the NH stretching band with axial deformation of
      the amide C=O group at about 1639 cm-1, NH angular deformation at approximately
      1560 cm-1; axial deformation of amide-CN at around 1421 cm-1, symmetrical angular
      deformation in CH3 at 1379 cm-1, -CN axial deformation of amino groups from 1125
      to 1250 cm-1 and polysaccharide structure bands in the range of between 890-1150
      cm-1. The crystallinity index of chitosan was 60.92%, and its degree of
      deacetylation was 75.25%. A low percentage of a supply of sucrose and asparagine
      with corn steep liquor offered higher yields of biomass and chitosan production
      at low cost.

PMID- 23973988
TI  - Palladium and organocatalysis: an excellent recipe for asymmetric synthesis.
AB  - The dual activation of simple substrates by the combination of organocatalysis
      and palladium catalysis has been successfully applied in a variety of different
      asymmetric transformations. Thus, the asymmetric a-allylation of carbonyl
      compounds, a-fluorination of acyl derivatives, decarboxylative protonation of
      beta-dicarbonyl compounds, cyclization reactions of alkynyl carbonyl compounds
      and beta-functionalization of aldehydes have been efficiently achieved employing
      this double-catalytic methodology. 

PMID- 23973989
TI  - Variation of vitamin D in cow's milk and interaction with beta-lactoglobulin.
AB  - Vitamin D is the collective name for a group of closely related lipids, whose
      main biological function is to maintain serum calcium and phosphorus
      concentrations within the normal range by enhancing the efficiency of the small
      intestine to absorb these minerals from the diet. We used a commercially
      available ELISA method for the determination of vitamin D in bovine milk.
      Individual milk samples from two different Italian Friesian herds were analysed.
      The enzyme immunoassay method used was confirmed as a useful tool to measure the
      vitamin D in the milk as it greatly reduces the time required to perform the
      conventional HPLC analysis. An interesting variation was found among individual
      animals that may be associated with management factors and specific genetic
      effects. A relationship was highlighted between vitamin D and the genetic
      polymorphism of beta-lactoglobulin, the main bovine whey protein which is
      involved in the transport of small hydrophobic molecules such as retinol and
      vitamin D. The relatively high content of vitamin D in most milk samples suggests
      an opportunity to improve the natural content of vitamin D in milk either by
      acting on the herd management or selecting individuals genetically predisposed to
      produce milk with a higher vitamin D content. 

PMID- 23973990
TI  - Cyclooxygenase-2 (COX-2) inhibition constrains indoleamine 2,3-dioxygenase 1
      (IDO1) activity in acute myeloid leukaemia cells.
AB  - Indoleamine 2,3-dioxygenase 1 (IDO1) metabolizes L-tryptophan to kynurenines
      (KYN), inducing T-cell suppression either directly or by altering antigen
      presenting-cell function. Cyclooxygenase (COX)-2, the rate-limiting enzyme in the
      synthesis of prostaglandins, is over-expressed by several tumours. We aimed at
      determining whether COX-2 inhibitors down-regulate the IFN-g-induced expression
      of IDO1 in acute myeloid leukaemia (AML) cells. IFN-gamma at 100 ng/mL up
      regulated COX-2 and IDO1 in HL-60 AML cells, both at mRNA and protein level. The
      increased COX-2 and IDO1 expression correlated with heightened production of
      prostaglandin (PG)E2 and kynurenines, respectively. Nimesulide, a preferential
      COX-2 inhibitor, down-regulated IDO1 mRNA/protein and attenuated kynurenine
      synthesis, suggesting that overall IDO inhibition resulted both from reduced IDO1
      gene transcription and from inhibited IDO1 catalytic activity. From a functional
      standpoint, IFN-g-challenged HL-60 cells promoted the in vitro conversion of
      allogeneic CD4+CD25- T cells into bona fide CD4+CD25+FoxP3+ regulatory T cells,
      an effect that was significantly reduced by treatment of IFN-gamma-activated HL
      60 cells with nimesulide. Overall, these data point to COX-2 inhibition as a
      potential strategy to be pursued with the aim at circumventing leukaemia-induced,
      IDO-mediated immune dysfunction.

PMID- 23973991
TI  - Sinulariolide induced hepatocellular carcinoma apoptosis through activation of
      mitochondrial-related apoptotic and PERK/eIF2alpha/ATF4/CHOP pathway.
AB  - Sinulariolide, an active compound isolated from the cultured soft coral Sinularia
      flexibilis, has potent anti-microbial and anti-tumorigenesis effects towards
      melanoma and bladder cancer cells. In this study, we investigated the effects of
      sinulariolide on hepatocellular carcinoma (HCC) cell growth and protein
      expression. Sinulariolide suppressed the proliferation and colony formation of
      HCC HA22T cells in a dose-dependent manner and induced both early and late
      apoptosis according to flow cytometry, Annexin V/PI stain and TUNEL/DAPI stain
      analyses. A mechanistic analysis demonstrated that sinulariolide-induced
      apoptosis was activated through a mitochondria-related pathway, showing up
      regulation of Bax, Bad and AIF, and down- regulation of Bcl-2, Bcl-xL, MCl-1 and
      p-Bad. Sinulariolide treatment led to loss of the mitochondrial membrane
      potential, release of mitochondrial cytochrome c to the cytosol, and activation
      of both caspase-9 and caspase-3. Sinulariolide-induced apoptosis was
      significantly blocked by the caspase inhibitors Z-VAD-FMK and Z-DEVD-FMK. The
      increased expression of cleaved PARP also suggested that caspase-independent
      apoptotic pathway was involved. In the western blotting; the elevation of ER
      chaperones GRP78; GRP94; and CALR; as well as up-regulations of
      PERK/eIF2alpha/ATF4/CHOP; and diminished cell death with pre-treatment of
      eIF2alpha phosphatase inhibitor; salubrinal; implicated the involvement of ER
      stress-mediated PERK/eIF2alpha/ATF4/CHOP apoptotic pathway following
      sinulariolide treatment in hepatoma cells. The current study suggested
      sinulariolide-induced hepatoma cell cytotoxicity involved multiple apoptotic
      signal pathways. This may implicate that sinulariolide is a potential compound
      for the treatment of hepatocellular carcinoma. 

PMID- 23973993
TI  - Synthesis and anti-HBV activity of novel 3'-N-phenylsulfonyl docetaxel analogs.
AB  - Nine new 3'-N-phenylsulfonyl docetaxel analogs were synthesized in good yields
      from the key intermediate N-phenylsulfonyl oxazolidine via a six-step route.
      These analogs were tested for anti-hepatitis B virus (HBV) activity in vitro.
      Compounds 3e, 3g and 3j showed more potent inhibitory activity against HBeAg
      secretion than the positive control lamivudine. Further extensive SAR and
      mechanistic studies will be reported in due course. 

PMID- 23973994
TI  - Comparison of two methods, UHPLC-UV and UHPLC-MS/MS, for the quantification of
      polyphenols in cider apple juices.
AB  - The aim of this study was to develop faster and more efficient phenotyping
      methods for in-depth genetic studies on cider apple progeny. The UHPLC
      chromatographic system was chosen to separate polyphenolic compounds, and
      quantifications were then simultaneously performed with a UV-PDA detector and an
      ESI-triple quadrupole mass analyzer (SRM mode). Both quantification methods were
      validated for 15 major compounds using two apple juice samples, on the basis of
      linearity, limits of detection and quantification, recovery and precision tests.
      The comparison between UV and SRM quantifications in 120 different samples of a
      cider apple progeny showed an excellent correlation for major compounds
      quantified with both methods. However, an overestimation was revealed for five
      compounds with the UV detector and the mass analyzer. Co-elution and matrix
      effects are discussed to explain this phenomenon. SRM methods should therefore be
      considered with restrictions in some cases for quantification measurements when
      several phenolic compounds are simultaneously quantified in complex matrices such
      as apple juices. For both methods, analyses were carried out over short periods
      of time while maintaining a high quality for the simultaneous quantification of
      phenolic compounds in apple juice. Each method is relevant for more in-depth
      genetic studies of the polyphenol content of apple juice. 

PMID- 23973992
TI  - Protein structure validation and identification from unassigned residual dipolar
      coupling data using 2D-PDPA.
AB  - More than 90% of protein structures submitted to the PDB each year are homologous
      to some previously characterized protein structure. The extensive resources that
      are required for structural characterization of proteins can be justified for the
      10% of the novel structures, but not for the remaining 90%. This report presents
      the 2D-PDPA method, which utilizes unassigned residual dipolar coupling in order
      to address the economics of structure determination of routine proteins by
      reducing the data acquisition and processing time. 2D-PDPA has been demonstrated
      to successfully identify the correct structure of an array of proteins that range
      from 46 to 445 residues in size from a library of 619 decoy structures by using
      unassigned simulated RDC data. When using experimental data, 2D-PDPA successfully
      identified the correct NMR structures from the same library of decoy structures.
      In addition, the most homologous X-ray structure was also identified as the
      second best structural candidate. Finally, success of 2D-PDPA in identifying and
      evaluating the most appropriate structure from a set of computationally predicted
      structures in the case of a previously uncharacterized protein Pf2048.1 has been
      demonstrated. This protein exhibits less than 20% sequence identity to any
      protein with known structure and therefore presents a compelling and practical
      application of our proposed work. 

PMID- 23973995
TI  - A 3D QSAR study of betulinic acid derivatives as anti-tumor agents using topomer
      CoMFA: model building studies and experimental verification.
AB  - Betulinic acid (BA) is a natural product that exerts its cytotoxicity against
      various malignant carcinomas without side effects by triggering the mitochondrial
      pathway to apoptosis. Betulin (BE), the 28-hydroxyl analog of BA, is present in
      large amounts (up to 30% dry weight) in the outer bark of birch trees, and shares
      the same pentacyclic triterpenoid core as BA, yet exhibits no significant
      cytotoxicity. Topomer CoMFA studies were performed on 37 BA and BE derivatives
      and their in vitro anti-cancer activity results (reported as IC50 values) against
      HT29 human colon cancer cells in the present study. All derivatives share a
      common pentacyclic triterpenoid core and the molecules were split into three
      pieces by cutting at the C-3 and C-28 sites with a consideration toward
      structural diversity. The analysis gave a leave-one-out cross-validation q2 value
      of 0.722 and a non-cross-validation r2 value of 0.974, which suggested that the
      model has good predictive ability (q2 > 0.2). The contour maps illustrated that
      bulky and electron-donating groups would be favorable for activity at the C-28
      site, and a moderately bulky and electron-withdrawing group near the C-3 site
      would improve this activity. BE derivatives were designed and synthesized
      according to the modeling result, whereby bulky electronegative groups (maleyl,
      phthalyl, and hexahydrophthalyl groups) were directly introduced at the C-28
      position of BE. The in vitro cytotoxicity values of the given analogs against
      HT29 cells were consistent with the predicted values, proving that the present
      topomer CoMFA model is successful and that it could potentially guide the
      synthesis of new betulinic acid derivatives with high anti-cancer activity. The
      IC50 values of these three new compounds were also assayed in five other tumor
      cell lines. 28-O-hexahydrophthalyl BE exhibited the greatest anti-cancer
      activities and its IC50 values were lower than those of BA in all cell lines,
      excluding DU145 cells.

PMID- 23973996
TI  - Brefeldin a effectively inhibits cancer stem cell-like properties and MMP-9
      activity in human colorectal cancer Colo 205 cells.
AB  - Cancer stem cells (CSCs) are a small subset of cancer cells with indefinite
      potential for self-renewal and the capacity to drive tumorigenesis. Brefeldin A
      (BFA) is an antibiotic that is known to block protein transport and induce
      endoplasmic reticulum (ER) stress in eukaryotic cells, but its effects on
      colorectal CSCs are unknown. We investigated the inhibitory effect of BFA on
      human colorectal cancer Colo 205 cells. We found that BFA effectively reduced the
      survival of suspension Colo 205 cells (IC50 = ~15 ng/mL) by inducing apoptosis,
      and inhibited the clonogenic activity of Colo 205 CSCs in tumorsphere formation
      assay and soft agar colony formation assay in the same nanogram per milliliter
      range. We also discovered that at such low concentrations, BFA effectively
      induced endoplasmic reticulum (ER) stress response as indicated by the increased
      mRNA expression of ER stress-related genes, such as glucose-regulated protein 78
      (GRP78), X-box binding protein 1 (XBP1), and C/EBP homologous protein (CHOP).
      Finally, we found that BFA reduced the activity of matrix metallopeptidase 9 (MMP
      9). These findings suggest that BFA can effectively suppress the progression of
      colorectal cancer during the tumorigenesis and metastasis stages. These results
      may lead to the development of novel therapies for the treatment of colorectal
      cancer.

PMID- 23973997
TI  - Understanding the nucleophilic character and stability of the carbanions and
      alkoxides of 1-(9-anthryl)ethanol and derivatives.
AB  - The nucleophilic character and stability of the carbanions vs. alkoxides derived
      from 2,2,2-trifluoro-1-(9-anthryl)ethanol and 1-(9-anthryl)ethanol containing X
      electron-releasing and X electron-acceptor substituents attached to C-10, have
      been studied at the B3LYP/6-31+G(d,p) level of theory. Results analyzed in terms
      of the absolute gas-phase acidity, Fukui function, the local hard and soft acids
      and bases principle, and the molecular electrostatic potential, show that the
      central ring of the 9-anthryl group confers an ambident nucleophilic character
      and stabilizes the conjugated carbanion by electron-acceptor delocalization. 

PMID- 23973998
TI  - GABA(B)-agonistic activity of certain baclofen homologues.
AB  - Baclofen (1) is a potent and selective agonist for bicuculline-insensitive
      GABA(B) receptors and is used clinically as an antispastic and muscle relaxant
      agent. In the search for new bioactive chemical entities that bind specifically
      to GABA(B) receptors, we report here the synthesis of certain baclofen
      homologues, namely (R,S)-5-amino-3-arylpentanoic acid hydrochlorides (R,S)-1a-h
      as well as (R,S)-5-amino-3-methylpentanoic acid [(RS)-1i] to be evaluated as
      GABA(B)R agonists. Compound 1a is an agonist to GABA(B) receptors with an EC50
      value of 46 MUM on tsA201 cells transfected with GABA(B1b)/GABA(B2)/Gqz5, being
      the most active congener among all the synthesized compounds.

PMID- 23973999
TI  - Coating barium titanate nanoparticles with polyethylenimine improves cellular
      uptake and allows for coupled imaging and gene delivery.
AB  - Barium titanate nanoparticles (BT NP) belong to a class of second harmonic
      generating (SHG) nanoprobes that have recently demonstrated promise in biological
      imaging. Unfortunately, BT NPs display low cellular uptake efficiencies, which
      may be a problem if cellular internalization is desired or required for a
      particular application. To overcome this issue, while concomitantly developing a
      particle platform that can also deliver nucleic acids into cells, we coated the
      BT NPs with the cationic polymer polyethylenimine (PEI)-one of the most effective
      nonviral gene delivery agents. Coating of BT with PEI yielded complexes with
      positive zeta potentials and resulted in an 8-fold increase in cellular uptake of
      the BT NPs. Importantly, we were able to achieve high levels of gene delivery
      with the BT-PEI/DNA complexes, supporting further efforts to generate BT
      platforms for coupled imaging and gene therapy. 

PMID- 23974000
TI  - Formulation optimization of palm kernel oil esters nanoemulsion-loaded with
      chloramphenicol suitable for meningitis treatment.
AB  - Palm kernel oil esters nanoemulsion-loaded with chloramphenicol was optimized
      using response surface methodology (RSM), a multivariate statistical technique.
      Effect of independent variables (oil amount, lecithin amount and glycerol amount)
      toward response variables (particle size, polydispersity index, zeta potential
      and osmolality) were studied using central composite design (CCD). RSM analysis
      showed that the experimental data could be fitted into a second-order polynomial
      model. Chloramphenicol-loaded nanoemulsion was formulated by using high pressure
      homogenizer. The optimized chloramphenicol-loaded nanoemulsion response values
      for particle size, PDI, zeta potential and osmolality were 95.33nm, 0.238, 
      36.91mV, and 200mOsm/kg, respectively. The actual values of the formulated
      nanoemulsion were in good agreement with the predicted values obtained from RSM.
      The results showed that the optimized compositions have the potential to be used
      as a parenteral emulsion to cross blood-brain barrier (BBB) for meningitis
      treatment. 

PMID- 23974001
TI  - The pH-sensitive polyampholyte nanogels: inclusion of carbon nanotubes for
      improved drug loading.
AB  - We report a simple and facile method to prepare a novel pH sensitive
      polyampholyte nanogel by copolymerizing vinylimidazole (VIM) with acrylic acid
      (AA) using functionalized single-walled carbon nanotubes (f-SWCNTs) (as
      reinforcing material) and cyanuric chloride via an intermolecular quaternization
      reaction. The polyampholyte nanogels have been characterized by various
      microscopic and spectroscopic methods. These studies reveal that incorporation of
      nanotubes in cross-linked copolymer of poly(vinylimidazole-co-acrylic acid) (PVI
      co-AA) form polyampholyte nanogel with enhanced physical properties. The thermal
      experiments show that the introduction of f-SWCNTs into PVI-co-AA has significant
      impact on the thermal stability of nanogels. The rheological study showed that
      the nanogel is more viscoelastic than native gel. MTT assay indicates that the
      prepared polyampholyte gels possess biocompatibility and cell viability. The
      nanogel is also useful material to load water-soluble drug such as promethazine
      hydrochloride. The releasing profile of the drug from the nanogel clearly shows
      the pH-sensitive property of the material. 

PMID- 23974002
TI  - Surface functionalization of styrenic block copolymer elastomeric biomaterials
      with hyaluronic acid via a "grafting to" strategy.
AB  - As a biostable elastomer, the hydrophobicity of styrenic block copolymer (SBC)
      intensely limits its biomedical applications. In order to overcome such
      shortcoming, the SBC films were grafted with hyaluronic acid (HA) using a
      coupling agent. The surface chemistry of the modified films was examined by ATR
      FTIR and XPS techniques, and the surface morphology was visually described by
      AFM. The biological performances of the HA-modified films were evaluated by a
      series of experiments, such as protein adsorption, platelet adhesion, and in
      vitro cytocompatibility. It was found that the HA-modified samples showed a low
      adhesiveness to fibroblast at the initial stage; however, it stimulated the
      growth of fibroblast. The L929 fibroblast growth presented a strong dependence on
      the molecular weight (MW) of HA. The samples modified with 17kDa HA exhibited the
      worst wettability and platelet adhesion, while providing the best results of
      supporting fibroblast proliferation. 

PMID- 23974003
TI  - Photo-mediated internalization of nanocomplex for effective gene delivery to
      adipose tissue-derived stem cells.
AB  - To deliver efficiently osteogenic, chondrogenic or adipogenic induction genes,
      such as Runx2, SOX9 and C/EBP-alpha, to adipose tissue-derived stem cells
      (ADSCs), a photo-mediated nanocomplex internalization gene delivery system was
      designed using chlorin e6 as a photosensitizer (PS) and polyethyleneimine (PEI)
      as a gene delivery carrier. In this system, gene delivery efficacy was
      significantly increased in ADSCs by photo irradiation. The gene transfection
      efficiency of Runx2, SOX9 and C/EBP-alpha was increased by 8.6-, 6.7- and 9.3
      fold, respectively, by applying 0.7J/cm(2) of irradiation. Osteogenic,
      chondrogenic and adipogenic differentiation was confirmed by differentiation
      related markers and histological analysis. ADSCs transfected with Runx2, SOX9 and
      C/EBP-alpha genes via photo irradiation indicated enhanced differentiation in
      comparison to the non-irradiated cells. These findings demonstrate that photo
      mediated internalization is a promising system for efficient gene delivery and
      differentiation in ADSCs. 

PMID- 23974004
TI  - Solid-support immobilization of a "swing" fusion protein for enhanced glucose
      oxidase catalytic activity.
AB  - The strategic surface immobilization of a protein can add new functionality to a
      solid substrate; however, protein activity, e.g., enzymatic activity, can be
      drastically decreased on immobilization onto a solid surface. The concept of a
      designed and optimized "molecular interface" is herein introduced in order to
      address this problem. In this study, molecular interface was designed and
      constructed with the aim of attaining high enzymatic activity of a solid-surface
      immobilized a using the hydrophobin HFBI protein in conjunction with a fusion
      protein of HFBI attached to glucose oxidase (GOx). The ability of HFBI to form a
      self-organized membrane on a solid surface in addition to its adhesion properties
      makes it an ideal candidate for immobilization. The developed fusion protein was
      also able to form an organized membrane, and its structure and immobilized state
      on a solid surface were investigated using QCM-D measurements. This method of
      immobilization showed retention of high enzymatic activity and the ability to
      control the density of the immobilized enzyme. In this study, we demonstrated the
      importance of the design and construction of molecular interface for numerous
      purposes. This method of protein immobilization could be utilized for preparation
      of high throughput products requiring structurally ordered molecular interfaces,
      in addition to many other applications. 

PMID- 23974005
TI  - Synthesis of strongly green-photoluminescent graphene quantum dots for drug
      carrier.
AB  - A novel approach has been developed for the preparation of strongly green
      photoluminescent graphene quantum dots (GQDs-PEG) which have been surface
      passivated by polyethylene glycol. The photoluminescence (PL) quantum yield of
      the GQDs-PEG with 400 nm excitation was about 18.8%, which was higher than other
      GQDs reported in the literature. More importantly, the surface-passivated PEG on
      GQDs can not only enhance PL intensity but also load drug by hydrogen bonding.
      Moreover, the high specific surface area of GQDs-PEG endowed them high loading
      capability (2.5 mg/mg) to carry drug. The results demonstrated that the GQDs-PEG
      were suitable for drug carrier and cell imaging. 

PMID- 23974006
TI  - RG7212 anti-TWEAK mAb inhibits tumor growth through inhibition of tumor cell
      proliferation and survival signaling and by enhancing the host antitumor immune
      response.
AB  - PURPOSE: To explore the role of TWEAK in tumor growth and antitumor immune
      response and the activity and mechanism of RG7212, an antagonistic anti-TWEAK
      antibody, in tumor models. EXPERIMENTAL DESIGN: TWEAK-induced signaling and gene
      expression were explored in tumor cell lines and inhibition of these effects and
      antitumor efficacy with RG7212 treatment was assessed in human tumor xenograft-,
      patient-derived xenograft, and syngeneic tumor models and phase I patients.
      Genetic features correlated with antitumor activity were characterized. RESULTS:
      In tumor cell lines, TWEAK induces proliferation, survival, and NF-kappaB
      signaling and gene expression that promote tumor growth and suppress antitumor
      immune responses. TWEAK-inducible CD274, CCL2, CXCL-10 and -11 modulate T-cell
      and monocyte recruitment, T-cell activation, and macrophage differentiation.
      These factors and TWEAK-induced signaling were decreased, and tumor, blood, and
      spleen immune cell composition was altered with RG7212 treatment in mice. RG7212
      inhibits tumor growth in vivo in models with TWEAK receptor, Fn14, expression,
      and markers of pathway activation. In phase I testing, signs of tumor shrinkage
      and stable disease were observed without dose-limiting toxicity. In a patient
      with advanced, Fn14-positive, malignant melanoma with evidence of tumor
      regression, proliferation markers were dramatically reduced, tumor T-cell
      infiltration increased, and tumor macrophage content decreased. Antitumor
      activity, a lack of toxicity in humans and animals and no evidence of antagonism
      with standard of care or targeted agents in mice, suggests that RG7212 is a
      promising agent for use in combination therapies in patients with Fn14-positive
      tumors.

PMID- 23974007
TI  - The epidemiology and resuscitation effects of cardiopulmonary arrest among
      hospitalized children and adolescents in Beijing: an observational study.
AB  - AIM: To investigate the epidemiology and resuscitation effects of cardiopulmonary
      arrest among hospitalized children and adolescents in Beijing. METHODS: A
      prospective multicentre study was conducted in four hospitals in urban/suburban
      areas of Beijing. Patients aged 1 month-18 years with cardiopulmonary arrest and
      received cardiopulmonary resuscitation (CPR) who were consecutively hospitalised
      during the study period (1 September 2008-31 December 2010) were enrolled. Data
      was collected and analyzed using the "in-hospital Utstein style". Neurological
      outcome was assessed with the pediatric cerebral performance category (PCPC)
      among patients who survived. RESULT: 201 of 108,673 hospitalized patients (0.18%)
      had cardiopulmonary arrest during their hospitalization. Of these, 174 patients
      underwent CPR. The most common causes of cardiopulmonary arrest were the diseases
      of respiratory system (29.3%) and circulatory system (19.0%). The most common
      initial rhythm was bradycardia (72.4%). About 108 patients (62.1%) had
      restoration of spontaneous circulation (ROSC). Forty-nine patients (28.2%)
      survived to hospital discharge, 25 (14.5%) survived 6 months post discharge, and
      21 (12.1%) survived 1 year post discharge. Out of the 21 patients who survived 1
      year after hospital discharge, 18 had good neurological outcome. Multivariate
      logistic regression analysis showed age, duration of CPR and endotracheal
      intubation performed before cardiopulmonary arrest were independent factors of
      cardiopulmonary resuscitation effect. CONCLUSION: The prevalence of in-hospital
      cardiopulmonary arrest in children and adolescents is low. The long-term result
      of children and adolescents survived from cardiopulmonary resuscitation is quite
      good. Age, CPR duration and endotracheal intubation performed before
      cardiopulmonary arrest were independent factors of cardiopulmonary resuscitation
      effect.

PMID- 23974008
TI  - Synaptic acetylcholinesterase targeted by microRNA-212 functions as a tumor
      suppressor in non-small cell lung cancer.
AB  - Acetylcholinesterase expression is modulated in various types of tumor, which
      suggests it is associated with tumor development; however, the mechanism of
      acetylcholinesterase gene regulation in tumors remains unclear. Here, we report
      that acetylcholinesterase is aberrantly expressed in non-small cell lung cancer
      and is an evolutionarily conserved functional target of miR-212.
      Acetylcholinesterase expression was negatively regulated by miR-212 in vitro and
      was inversely correlated with miR-212 expression in vivo. In addition,
      acetylcholinesterase levels were increased, and miR-212 levels decreased, in non
      small cell lung cancer cells during cisplatin-induced apoptosis. We further
      determined that acetylcholinesterase acted as a pro-apoptotic gene in non-small
      cell lung cells; and attenuated the growth of xenografts in nude mice when
      upregulated. In contrast, elevated miR-212 levels preserved the protective effect
      of acetylcholinesterase silencing by RNA interference against cisplatin-induced
      apoptosis, whereas restoration of miR-212-resistant synaptic acetylcholinesterase
      expression inhibited the miR-212 anti-apoptotic function. The results
      demonstrated that miR-212 exerted an anti-apoptotic effect through direct
      repression of synaptic acetylcholinesterase expression in non-small cell lung
      cancer cells. Taken together, our study revealed that synaptic
      acetylcholinesterase may be a tumor suppressor and is modulated by miR-212 in non
      small cell lung cancer. 

PMID- 23974010
TI  - In vivo site-specific integration of transgene in silkworm via PhiC31 integrase
      mediated cassette exchange.
AB  - Current techniques for genetic engineering of the silkworm Bombyx mori genome
      utilize transposable elements, which result in positional effects and insertional
      mutagenesis through random insertion of exogenous DNA. New methods for
      introducing transgenes at specific positions are therefore needed to overcome the
      limitations of transposon-based strategies. Although site-specific recombination
      systems have proven powerful tools for genome manipulation in many organisms,
      their use has not yet been well established for the integration of transgenes in
      the silkworm. We describe a method for integrating target genes at pre-defined
      chromosomal sites in the silkworm via phiC31/att site-specific recombination
      system-mediated cassette exchange. Successful recombinase-mediated cassette
      exchange (RMCE) was observed in the two transgenic target strains with an
      estimated transformation efficiency of 3.84-7.01%. Our results suggest that RMCE
      events between chromosomal attP/attP target sites and incoming attB/attB sites
      were more frequent than those in the reciprocal direction. This is the first
      report of in vivo RMCE via phiC31 integrase in the silkworm, and thus represents
      a key step toward establishing genome manipulation technologies in silkworms and
      other lepidopteran species.

PMID- 23974009
TI  - Coordinate H3K9 and DNA methylation silencing of ZNFs in toxicant-induced
      malignant transformation.
AB  - Genome-wide disruption of the epigenetic code is a hallmark of malignancy that
      encompasses many distinct, highly interactive modifications. Delineating the
      aberrant epigenome produced during toxicant-mediated malignant transformation
      will help identify the underlying epigenetic drivers of environmental toxicant
      induced carcinogenesis. Gene promoter DNA methylation and gene expression
      profiling of arsenite-transformed prostate epithelial cells showed a negative
      correlation between gene expression changes and DNA methylation changes; however,
      less than 10% of the genes with increased promoter methylation were
      downregulated. Studies described herein confirm that a majority of the DNA
      hypermethylation events occur at H3K27me3 marked genes that were already
      transcriptionally repressed. In contrast to aberrant DNA methylation targeting
      H3K27me3 pre-marked silent genes, we found that actively expressed C2H2 zinc
      finger genes (ZNFs) marked with H3K9me3 on their 3' ends, were the favored
      targets of DNA methylation linked gene silencing. DNA methylation coupled,
      H3K9me3 mediated gene silencing of ZNF genes was widespread, occurring at
      individual ZNF genes on multiple chromosomes and across ZNF gene family clusters.
      At ZNF gene promoters, H3K9me3 and DNA hypermethylation replaced H3K4me3,
      resulting in a widespread downregulation of ZNF gene expression, which accounted
      for 8% of all the downregulated genes in the arsenical-transformed cells. In
      summary, these studies associate toxicant exposure with widespread silencing of
      ZNF genes by DNA hypermethylation-linked H3K9me3 spreading, further implicating
      epigenetic dysfunction as a driver of toxicant associated carcinogenesis. 

PMID- 23974011
TI  - Regulation of atrophin by both strands of the mir-8 precursor.
AB  - In Drosophila melanogaster, miR-8-3p regulates mRNA levels of atrophin, a factor
      involved in neuromotor coordination, and we found that Blattella germanica with
      suppressed atrophin showed motor problems. Bionformatic predictions and
      luciferase-reporter tests indicated that B. germanica atrophin mRNA contains
      target sites for miR-8-3p and miR-8-5p. Suppression of miR-8-3p or miR-8-5p
      appeared to increase atrophin mRNA. The effects of suppression of Argonaute (AGO)
      1 or AGO2 expression on miR-8-3p and miR-8-5p suggested that miR-8-3-p might
      predominantly bind to AGO1, whereas miR-8-5p might bind to a moderate extent to
      both AGO1 and AGO2 in the respective RNA-induced silencing complexes (RISCs). We
      propose that the interplay of miR-8-3p, miR-8-5p, AGO1 and AGO2, maintain the
      appropriate levels of atrophin mRNA. This would be the first example of two
      strands of the same miRNA precursor regulating a single transcript.

PMID- 23974012
TI  - Interaction between mosquito-larvicidal Lysinibacillus sphaericus binary toxin
      components: analysis of complex formation.
AB  - The two components (BinA and BinB) of Lysinibacillus sphaericus binary toxin
      together are highly toxic to Culex and Anopheles mosquito larvae, and have been
      employed world-wide to control mosquito borne diseases. Upon binding to the
      membrane receptor an oligomeric form (BinA2.BinB2) of the binary toxin is
      expected to play role in pore formation. It is not clear if these two proteins
      interact in solution as well, in the absence of receptor. The interactions
      between active forms of BinA and BinB polypeptides were probed in solution using
      size-exclusion chromatography, pull-down assay, surface plasmon resonance,
      circular dichroism, and by chemically crosslinking BinA and BinB components. We
      demonstrate that the two proteins interact weakly with first association and
      dissociation rate constants of 4.5*10(3) M(-1) s(-1) and 0.8 s(-1), resulting in
      conformational change, most likely, in toxic BinA protein that could kinetically
      favor membrane translocation of the active oligomer. The weak interactions
      between the two toxin components could be stabilized by glutaraldehyde
      crosslinking. The cross-linked complex, interestingly, showed maximal Culex
      larvicidal activity (LC50 value of 1.59 ng mL(-1)) reported so far for
      combination of BinA/BinB components, and thus is an attractive option for
      development of new bio-pesticides for control of mosquito borne vector diseases.

PMID- 23974013
TI  - Substrate-based peptidomimetic inhibitors of the Murray Valley encephalitis virus
      NS2B/NS3 serine protease: a P1-P4 SAR study.
AB  - Murray Valley encephalitis is an infectious disease spread by a mosquito-borne
      virus endemic in Papua New Guinea and northern Australia. In the past decade, it
      has spread to various regions of Australia and there is currently no therapeutic
      treatment against this disease. An attractive drug target is the viral serine
      protease NS2B/NS3, a critical enzyme involved in viral replication. Herein, we
      report the inhibitory activities of 37 C-terminal agmatine peptidomimetic
      inhibitors which led to the design of a novel structurally-constrained
      competitive inhibitor 38 possessing a Ki of 2.5+/-0.5 MUM. We believe our data
      provides crucial insights into the viral protease active site specificity which
      could be used to facilitate drug design against Murray Valley encephalitis viral
      infections.

PMID- 23974014
TI  - Toward the design of new DNA G-quadruplex ligands through rational analysis of
      polymorphism and binding data.
AB  - Human telomeres play a key role in protecting chromosomal ends from fusion
      events; they are composed of d(TTAGGG) repeats, ranging in size from 3 to 15 kb.
      They form G-quadruplex DNA structures, stabilized by G-quartets in the presence
      of cations, and are involved in several biological processes. In particular, a
      telomere maintenance mechanism is provided by a specialized enzyme called
      telomerase, a reverse transcriptase able to add multiple copies of the 5'-GGTTAG
      3' motif to the end of the G-strand of the telomere and which is over-expressed
      in the majority of cancer cells. The central cation has a crucial role in
      maintaining the stability of the structure. Based on its nature, it can be
      associated with different topological telomeric quadruplexes, which depend also
      on the orientation of the DNA strands and the syn/anti conformation of the
      guanines. Such a polymorphism, confirmed by the different structures deposited in
      the Protein Data Bank (PDB), prompted us to apply a computational protocol in
      order to investigate the conformational properties of a set of known G-quadruplex
      ligands and their molecular recognition against six different experimental models
      of the human telomeric sequence d[AG3(T2AG3)3]. The average AutoDock correlation
      between theoretical and experimental data yielded an r2 value equal to 0.882
      among all the studied models. Such a result was always improved with respect to
      those of the single folds, with the exception of the parallel structure (r2 equal
      to 0.886), thus suggesting a key role of this G4 conformation in the stacking
      interaction network. Among the studied binders, a trisubstituted acridine and a
      dibenzophenanthroline derivative were well recognized by the parallel and the
      mixed G-quadruplex structures, allowing the identification of specific key
      contacts with DNA and the further design of more potent or target specific G
      quadruplex ligands.

PMID- 23974015
TI  - 2,3,9- and 2,3,11-trisubstituted tetrahydroprotoberberines as D2 dopaminergic
      ligands.
AB  - Dopamine-mediated neurotransmission plays an important role in relevant
      psychiatric and neurological disorders. Nowadays, there is an enormous interest
      in the development of new dopamine receptors (DR) acting drugs as potential new
      targets for the treatment of schizophrenia or Parkinson's disease. Previous
      studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines
      (THIQs) and tetrahydroprotoberberines (THPBs) can behave as selective D2
      dopaminergic alkaloids since they share structural similarities with dopamine. In
      the present study we have synthesized eleven 2,3,9- and 2,3,11-trisubstituted
      THPB compounds (six of them are described for the first time) and evaluated their
      potential dopaminergic activity. Binding studies on rat striatal membranes were
      used to evaluate their affinity and selectivity towards D1 and D2 DR and
      establish the structure-activity relationship (SAR) as dopaminergic agents. In
      general, all the tested THPBs with protected phenolic hydroxyls showed a lower
      affinity for D1 and D2 DR than their corresponding homologues with free hydroxyl
      groups. In previous studies in which dopaminergic affinity of 1-benzyl-THIQs
      (BTHIQs) was evaluated, the presence of a Cl into the A-ring resulted in
      increased affinity and selectivity towards D2 DR. This is in contrast with the
      current study since the existence of a chlorine atom into the A-ring of the THPBs
      caused increased affinity for D1 DR but dramatically reduced the selectivity for
      D2 DR. An OH group in position 9 of the THPB (9f) resulted in a higher affinity
      for DR than its homologue with an OH group in position 11 (9e) (250 fold for D2
      DR). None of the compounds showed any cytotoxicity in freshly isolated human
      neutrophils. A molecular modelling study of three representative THPBs was
      carried out. The combination of MD simulations with DFT calculations provided a
      clear picture of the ligand binding interactions from a structural and energetic
      point of view. Therefore, it is likely that compound 9d (2,3,9-trihydroxy-THPB)
      behave as D2 DR agonist since serine residues cluster are crucial for agonist
      binding and receptor activation. 

PMID- 23974016
TI  - Hybrid peptides endomorphin-2/DAMGO: design, synthesis and biological evaluation.
AB  - Endomorphin-2 [Tyr-Pro-Phe-Phe-NH2] and DAMGO [Tyr-D-Ala-Gly-(N-Me)Phe-Gly-ol]
      are natural (EM2) and synthetic (DAMGO) opioid peptides both selective for MU
      opioid receptor with high analgesic activity. In this work we report synthesis,
      in vitro and in vivo biological evaluation of five new hybrid EM2/DAMGO
      analogues, with the aim to obtain compounds with high affinity at MU-opioid
      receptor, high activity in animal nociception tests (hot plate and tail flick)
      and improved enzymatic stability. Double N-methylation on both Phe residues and C
      terminal ethanolamide led to analogue 6e, which possesses a good in vitro MU
      affinity (KiMU=34 nM), combined with a remarkable in vivo antinociceptive
      activity.

PMID- 23974017
TI  - Small azobenzene derivatives active against bacteria and fungi.
AB  - ATP synthase and protein kinase (PKs) are prime targets for drug discovery in a
      variety of diseases. It is well known that numerous stilbenes are capable to
      interact and inhibit ATP synthase and PKs. This work focuses on a series of
      azobenzene based molecules having high structural similarity with antimicrobial
      stilbenes. An investigation was carried out analyzing the potential toxicity of a
      large set of molecules by means of computational analysis. A small selection of
      potential low toxic molecules have been therefore synthesized, characterized and
      finally microbiologically tested. The synthesized compounds show potent
      bactericidal activity against Gram+ and a fungus, and are capable of inhibiting
      biofilm formation. Finally, the compounds demonstrated a thermal stability that
      makes them potential candidates for incorporation in polymer matrix for
      application as biomedical devices and food packaging. 

PMID- 23974018
TI  - Mannich bases of 7-piperazinylquinolones and kojic acid derivatives: synthesis,
      in vitro antibacterial activity and in silico study.
AB  - Novel Mannich bases of 7-piperazinylquinolones with kojic acid and chlorokojic
      acid were designed as new quinolone antibacterials. All compounds showed
      significant in vitro antibacterial activity against both Gram-positive and Gram
      negative bacteria. Particularly, chlorokojic derivative 2b was the most potent
      compound against Staphylococcus aureus and Pseudomonas aeruginosa (MIC
      values<=0.19 MUg/mL). Its activity was 4-8 times more than that of standard drug
      norfloxacin. The molecular docking study of compound 2b further supported the
      molecular basis of the designed compounds.

PMID- 23974019
TI  - A novel p-terphenyl derivative inducing cell-cycle arrest and apoptosis in MDA-MB
      435 cells through topoisomerase inhibition.
AB  - A novel series of p-terphenyl derivatives (1-4, 1a-4a) was successfully
      synthesized and their in vitro anticancer activities were evaluated. Compound 1,
      showing the best antiproliferative activity with IC50<1 MUM against MDA-MB-435
      cells, was further investigated. Compound 1 brought about a remarkable
      accumulation of MDA-MB-435 cells in G2/M phase prior to the induction of
      apoptosis. Further antitumor mechanism study indicated that compound 1, which
      inhibited the enzyme activity of Topo I and Topo IIalpha by interfering
      predominantly with the enzyme, could be topoisomerase suppressors instead of
      poisons. We conclude that compound 1 represents a novel class of Topo catalytic
      suppressors for developing new chemotherapeutic agents.

PMID- 23974020
TI  - Synthesis, transformation and biological evaluation of 2,3-secotriterpene
      acetylhydrazones and their derivatives.
AB  - It has been previously shown that semi-synthetic A-secotriterpene
      acetylhydrazones of 1-cyano-28-methoxy-28-oxo-2,3-seco-2-norlup-20(29)-en-3-al
      and 1-cyano-2,3-seco-2-nor-19beta,28-epoxy-18alphaH-olean-3-al (1, 2) inhibit the
      vesicular stomatitis virus (VSV) replication. To improve the antiviral activity
      against VSV, structural modifications of compounds 1 and 2 were performed, and
      new A-secoderivatives containing the acetylhydrazone fragment were obtained from
      betulonic acid and its methyl ester, allobetulone, and 3-oxo-18betaH
      glycyrrhetinic acid methyl ester. The inhibitory effects of these compounds on
      VSV replication in porcine embryo kidney (PEK) cells were determined after
      infection. It was shown that introduction of the 3'-acetyl-5'-methyl-1',3',4'
      oxadiazoline fragment into lupane triterpene structures lead to an increase in
      the antiviral activity of A-secotriterpene derivatives. However, the presence of
      a heterocyclic moiety enhanced toxic activity and reduced the therapeutic indices
      of these agents. Investigation in the anti-proliferative activity of the
      heterocyclic derivatives has shown high sensitivity of A-549, MS and RD tumor
      cell lines to lupane (R)-oxadiazoline 11a. The pro-apoptotic effect of 11a was
      confirmed by the AnnexinV/PI analysis. 

PMID- 23974021
TI  - Synthesis, molecular docking and kinetic properties of beta-hydroxy-beta
      phenylpropionyl-hydroxamic acids as Helicobacter pylori urease inhibitors.
AB  - Inhibition of urease results in Helicobacter pylori growth arrest in the stomach,
      promoting urease as promising targets for gastrointestinal ulcer therapy. Twenty
      hybrid derivatives of flavonoid scaffold and hydroxamic acid, beta-hydroxy-beta
      phenylpropionylhydroxamic acids, were therefore synthesized and evaluated against
      H. pylori urease. Biological evaluation of these compounds showed improved urease
      inhibition exhibiting micromolar to mid-nanomolar IC50 values. Most importantly,
      3-(3-chlorophenyl)-3-hydroxypropionyl-hydroxamic acid (6g) exhibited high potency
      with IC50 of 0.083+/-0.004 MUM and Ki of 0.014+/-0.003 MUM, indicating that 6g is
      an excellent candidate to develop novel antiulcer agent. A mixture of competitive
      and uncompetitive mechanism was putatively proposed to understand the
      inconsistency between the crystallographic and kinetic studies for the first
      time, which is supported by our molecular docking studies.

PMID- 23974022
TI  - Library screen identifies Enterococcus faecalis CcpA, the catabolite control
      protein A, as an effector of Ace, a collagen adhesion protein linked to
      virulence.
AB  - The Enterococcus faecalis cell wall-anchored protein Ace is an important
      virulence factor involved in cell adhesion and infection. Expression of Ace on
      the cell surface is affected by many factors, including stage of growth, culture
      temperature, and environmental components, such as serum, urine, and collagen.
      However, the mechanisms that regulate or modulate Ace display are not well
      understood. With interest in identifying genes associated with Ace expression, we
      utilized a whole-cell enzyme-linked immunosorbent assay (ELISA)-based screening
      method to identify mutants from a transposon insertion mutant library which
      exhibited distinct Ace surface expression profiles. We identified a ccpA
      insertion mutant which showed significantly decreased levels of Ace surface
      expression at early growth phase versus those of wild-type OG1RF. Confirmation of
      the observation was achieved through flow cytometry and complementation analysis.
      Compared to the wild type, the E. faecalis ccpA mutant had an impaired ability to
      adhere to collagen when grown to early exponential phase, consistent with the
      lack of Ace expression in the early growth phase. As a key component of carbon
      catabolite regulation, CcpA has been previously reported to play a critical role
      in regulating expression of proteins involved in E. faecalis carbohydrate uptake
      and utilization. Our discovery is the first to associate CcpA with the production
      of a major E. faecalis virulence factor, providing new insights into the
      regulation of E. faecalis pathogenesis. 

PMID- 23974023
TI  - Probing bacterial metabolism during infection using high-resolution
      transcriptomics.
AB  - A fundamental aspect of most infectious diseases is the need for the invading
      microbe to proliferate in the host. However, little is known about the metabolic
      pathways required for pathogenic microbes to colonize and persist in their hosts.
      In this study, we used RNA sequencing (RNA-seq) to generate a high-resolution
      transcriptome of the opportunistic pathogen Aggregatibacter actinomycetemcomitans
      in vivo. We identified 691 A. actinomycetemcomitans transcriptional start sites
      and 210 noncoding RNAs during growth in vivo and as a biofilm in vitro. Compared
      to in vitro biofilm growth on a defined medium, ~14% of the A.
      actinomycetemcomitans genes were differentially regulated in vivo. A
      disproportionate number of genes coding for proteins involved in metabolic
      pathways were differentially regulated in vivo, suggesting that A.
      actinomycetemcomitans in vivo metabolism is distinct from in vitro growth.
      Mutational analyses of differentially regulated genes revealed that formate
      dehydrogenase H and fumarate reductase are important A. actinomycetemcomitans
      fitness determinants in vivo. These results not only provide a high-resolution
      genomic analysis of a bacterial pathogen during in vivo growth but also provide
      new insight into metabolic pathways required for A. actinomycetemcomitans in vivo
      fitness. 

PMID- 23974024
TI  - Transposon mutagenesis identified chromosomal and plasmid genes essential for
      adaptation of the marine bacterium Dinoroseobacter shibae to anaerobic
      conditions.
AB  - Anaerobic growth and survival are integral parts of the life cycle of many marine
      bacteria. To identify genes essential for the anoxic life of Dinoroseobacter
      shibae, a transposon library was screened for strains impaired in anaerobic
      denitrifying growth. Transposon insertions in 35 chromosomal and 18 plasmid genes
      were detected. The essential contribution of plasmid genes to anaerobic growth
      was confirmed with plasmid-cured D. shibae strains. A combined transcriptome and
      proteome approach identified oxygen tension-regulated genes. Transposon insertion
      sites of a total of 1,527 mutants without an anaerobic growth phenotype were
      determined to identify anaerobically induced but not essential genes. A
      surprisingly small overlap of only three genes (napA, phaA, and the Na(+)/Pi
      antiporter gene Dshi_0543) between anaerobically essential and induced genes was
      found. Interestingly, transposon mutations in genes involved in dissimilatory and
      assimilatory nitrate reduction (napA, nasA) and corresponding cofactor
      biosynthesis (genomic moaB, moeB, and dsbC and plasmid-carried dsbD and ccmH)
      were found to cause anaerobic growth defects. In contrast, mutation of
      anaerobically induced genes encoding proteins required for the later
      denitrification steps (nirS, nirJ, nosD), dimethyl sulfoxide reduction (dmsA1),
      and fermentation (pdhB1, arcA, aceE, pta, acs) did not result in decreased
      anaerobic growth under the conditions tested. Additional essential components
      (ferredoxin, cccA) of the anaerobic electron transfer chain and central
      metabolism (pdhB) were identified. Another surprise was the importance of sodium
      gradient-dependent membrane processes and genomic rearrangements via viruses,
      transposons, and insertion sequence elements for anaerobic growth. These
      processes and the observed contributions of cell envelope restructuring (lysM,
      mipA, fadK), C4-dicarboxylate transport (dctM1, dctM3), and protease functions to
      anaerobic growth require further investigation to unravel the novel underlying
      adaptation strategies. 

PMID- 23974025
TI  - Dimerization of the Pseudomonas aeruginosa translocator chaperone PcrH is
      required for stability, not function.
AB  - Type III secretion systems rely on hydrophobic translocator proteins that form a
      pore in the host cell membrane to deliver effector proteins into targeted host
      cells. These translocator proteins are stabilized in the cytoplasm and targeted
      for export with the help of specific chaperone proteins. In Pseudomonas
      aeruginosa, the chaperone of the pore-forming translocator proteins is PcrH.
      Although all translocator chaperones dimerize, the location of the dimerization
      interface is in dispute. Moreover, it has been reported that interfering with
      dimerization interferes with chaperone function. However, binding of P.
      aeruginosa chaperone PcrH to its cognate secretion substrate, PopD, results in
      dissociation of the PcrH dimer in vitro, arguing that dimerization of PcrH is
      likely not important for substrate binding or targeting translocators for export.
      We demonstrate that PcrH dimerization occurs in vivo in P. aeruginosa and used a
      genetic screen to identify a dimerization mutant of PcrH. The mutant protein is
      fully functional in that it can both stabilize PopB and PopD in the cytoplasm and
      promote their export via the type III secretion system. The location of the
      mutation suggests that the dimerization interface of PcrH mirrors that of the
      Yersinia homolog SycD and not the dimerization interface that had previously been
      reported for PcrH based on crystallographic evidence. Finally, we present data
      that the dimerization mutant of PcrH is less stable than the wild-type protein in
      P. aeruginosa, suggesting that the function of dimerization is stabilization of
      PcrH in the absence of its cognate cargo. 

PMID- 23974026
TI  - Roles of HynAB and Ech, the only two hydrogenases found in the model sulfate
      reducer Desulfovibrio gigas.
AB  - Sulfate-reducing bacteria are characterized by a high number of hydrogenases,
      which have been proposed to contribute to the overall energy metabolism of the
      cell, but exactly in what role is not clear. Desulfovibrio spp. can produce or
      consume H2 when growing on organic or inorganic substrates in the presence or
      absence of sulfate. Because of the presence of only two hydrogenases encoded in
      its genome, the periplasmic HynAB and cytoplasmic Ech hydrogenases, Desulfovibrio
      gigas is an excellent model organism for investigation of the specific function
      of each of these enzymes during growth. In this study, we analyzed the
      physiological response to the deletion of the genes that encode the two
      hydrogenases in D. gigas, through the generation of DeltaechBC and DeltahynAB
      single mutant strains. These strains were analyzed for the ability to grow on
      different substrates, such as lactate, pyruvate, and hydrogen, under respiratory
      and fermentative conditions. Furthermore, the expression of both hydrogenase
      genes in the three strains studied was assessed through quantitative reverse
      transcription-PCR. The results demonstrate that neither hydrogenase is essential
      for growth on lactate-sulfate, indicating that hydrogen cycling is not
      indispensable. In addition, the periplasmic HynAB enzyme has a bifunctional
      activity and is required for growth on H2 or by fermentation of pyruvate.
      Therefore, this enzyme seems to play a dominant role in D. gigas hydrogen
      metabolism. 

PMID- 23974027
TI  - MacA, a periplasmic membrane fusion protein of the macrolide transporter MacAB
      TolC, binds lipopolysaccharide core specifically and with high affinity.
AB  - The Escherichia coli MacAB-TolC transporter has been implicated in efflux of
      macrolide antibiotics and secretion of enterotoxin STII. In this study, we found
      that purified MacA, a periplasmic membrane fusion protein, contains one tightly
      bound rough core lipopolysaccharide (R-LPS) molecule per MacA molecule. R-LPS was
      bound specifically to MacA protein with affinity exceeding that of polymyxin B.
      Sequence analyses showed that MacA contains two high-density clusters of
      positively charged amino acid residues located in the cytoplasmic N-terminal
      domain and the periplasmic C-terminal domain. Substitutions in the C-terminal
      cluster reducing the positive-charge density completely abolished binding of R
      LPS. At the same time, these substitutions significantly reduced the
      functionality of MacA in the protection of E. coli against macrolides in vivo and
      in the in vitro MacB ATPase stimulation assays. Taken together, our results
      suggest that R-LPS or a similar glycolipid is a physiological substrate of MacAB
      TolC. 

PMID- 23974028
TI  - Novel feature of Mycobacterium avium subsp. paratuberculosis, highlighted by
      characterization of the heparin-binding hemagglutinin adhesin.
AB  - Mycobacterium avium subsp. paratuberculosis comprises two genotypically defined
      groups, known as the cattle (C) and sheep (S) groups. Recent studies have
      reported phenotypic differences between M. avium subsp. paratuberculosis groups C
      and S, including growth rates, infectivity for macrophages, and iron metabolism.
      In this study, we investigated the genotypes and biological properties of the
      virulence factor heparin-binding hemagglutinin adhesin (HBHA) for both groups. In
      Mycobacterium tuberculosis, HBHA is a major adhesin involved in mycobacterium
      host interactions and extrapulmonary dissemination of infection. To investigate
      HBHA in M. avium subsp. paratuberculosis, we studied hbhA polymorphisms by
      fragment analysis using the GeneMapper technology across a large collection of
      isolates genotyped by mycobacterial interspersed repetitive-unit-variable-number
      tandem-repeat (MIRU-VNTR) and IS900 restriction fragment length polymorphism
      (RFLP-IS900) analyses. Furthermore, we analyzed the structure-function
      relationships of recombinant HBHA proteins of types C and S by heparin-Sepharose
      chromatography and surface plasmon resonance (SPR) analyses. In silico analysis
      revealed two forms of HBHA, corresponding to the prototype genomes for the C and
      S types of M. avium subsp. paratuberculosis. This observation was confirmed using
      GeneMapper on 85 M. avium subsp. paratuberculosis strains, including 67 strains
      of type C and 18 strains of type S. We found that HBHAs from all type C strains
      contain a short C-terminal domain, while those of type S present a long C
      terminal domain, similar to that produced by Mycobacterium avium subsp. avium.
      The purification of recombinant HBHA from M. avium subsp. paratuberculosis of
      both types by heparin-Sepharose chromatography highlighted a correlation between
      their affinities for heparin and the lengths of their C-terminal domains, which
      was confirmed by SPR analysis. Thus, types C and S of M. avium subsp.
      paratuberculosis may be distinguished by the types of HBHA they produce, which
      differ in size and adherence properties, thereby providing new evidence that
      strengthens the genotypic differences between the C and S types of M. avium
      subsp. paratuberculosis. 

PMID- 23974029
TI  - Measurements of mRNA degradation in Borrelia burgdorferi.
AB  - The importance of gene regulation in the enzootic cycle of Borrelia burgdorferi,
      the spirochete that causes Lyme disease, is well established. B. burgdorferi
      regulates gene expression in response to changes in environmental stimuli
      associated with changing hosts. In this study, we monitored mRNA decay in B.
      burgdorferi following transcriptional arrest with actinomycin D. The time
      dependent decay of transcripts encoding RNA polymerase subunits (rpoA and rpoS),
      ribosomal proteins (rpsD, rpsK, rpsM, rplQ, and rpsO), a nuclease (pnp), outer
      surface lipoproteins (ospA and ospC), and a flagellar protein (flaB) have
      different profiles and indicate half-lives ranging from approximately 1 min to
      more than 45 min in cells cultured at 35 degrees C. Our results provide a first
      step in characterizing mRNA decay in B. burgdorferi and in investigating its role
      in gene expression and regulation. 

PMID- 23974030
TI  - Complementation of the Fo c subunit of Escherichia coli with that of
      Streptococcus mutans and properties of the hybrid FoF1 ATP synthase.
AB  - The c subunit of Streptococcus mutans ATP synthase (FoF1) is functionally
      exchangeable with that of Escherichia coli, since E. coli with a hybrid FoF1 is
      able to grow on minimum succinate medium through oxidative phosphorylation. E.
      coli F1 bound to the hybrid Fo with the S. mutans c subunit showed N,N'
      dicyclohexylcarbodiimide-sensitive ATPase activity similar to that of E. coli
      FoF1. Thus, the S. mutans c subunit assembled into a functional Fo together with
      the E. coli a and b subunits, forming a normal F1 binding site. Although the H(+)
      pathway should be functional, as was suggested by the growth on minimum succinate
      medium, ATP-driven H(+) transport could not be detected with inverted membrane
      vesicles in vitro. This observation is partly explained by the presence of an
      acidic residue (Glu-20) in the first transmembrane helix of the S. mutans c
      subunit, since the site-directed mutant carrying Gln-20 partly recovered the ATP
      driven H(+) transport. Since S. mutans is recognized to be a primary etiological
      agent of human dental caries and is one cause of bacterial endocarditis, our
      system that expresses hybrid Fo with the S. mutans c subunit would be helpful to
      find antibiotics and chemicals specifically directed to S. mutans. 

PMID- 23974031
TI  - Flexibility of syntrophic enzyme systems in Desulfovibrio species ensures their
      adaptation capability to environmental changes.
AB  - The mineralization of organic matter in anoxic environments relies on the
      cooperative activities of hydrogen producers and consumers obligately linked by
      interspecies metabolite exchange in syntrophic consortia that may include sulfate
      reducing species such as Desulfovibrio. To evaluate the metabolic flexibility of
      syntrophic Desulfovibrio to adapt to naturally fluctuating methanogenic
      environments, we studied Desulfovibrio alaskensis strain G20 grown in chemostats
      under respiratory and syntrophic conditions with alternative methanogenic
      partners, Methanococcus maripaludis and Methanospirillum hungatei, at different
      growth rates. Comparative whole-genome transcriptional analyses, complemented by
      G20 mutant strain growth experiments and physiological data, revealed a
      significant influence of both energy source availability (as controlled by
      dilution rate) and methanogen on the electron transfer systems, ratios of
      interspecies electron carriers, energy generating systems, and interspecies
      physical associations. A total of 68 genes were commonly differentially expressed
      under syntrophic versus respiratory lifestyle. Under low-energy (low-growth-rate)
      conditions, strain G20 further had the capacity to adapt to the metabolism of its
      methanogenic partners, as shown by its differing gene expression of enzymes
      involved in the direct metabolic interactions (e.g., periplasmic hydrogenases)
      and the ratio shift in electron carriers used for interspecies metabolite
      exchange (hydrogen/formate). A putative monomeric [Fe-Fe] hydrogenase and Hmc
      (high-molecular-weight-cytochrome c3) complex-linked reverse menaquinone (MQ)
      redox loop become increasingly important for the reoxidation of the lactate
      /pyruvate oxidation-derived redox pair, DsrC(red) and Fd(red), relative to the
      Qmo-MQ-Qrc (quinone-interacting membrane-bound oxidoreductase; quinone-reducing
      complex) loop. Together, these data underscore the high enzymatic and metabolic
      adaptive flexibility that likely sustains Desulfovibrio in naturally fluctuating
      methanogenic environments.

PMID- 23974032
TI  - Pasteurella multocida Heddleston serovar 3 and 4 strains share a common
      lipopolysaccharide biosynthesis locus but display both inter- and intrastrain
      lipopolysaccharide heterogeneity.
AB  - Pasteurella multocida is a Gram-negative multispecies pathogen and the causative
      agent of fowl cholera, a serious disease of poultry which can present in both
      acute and chronic forms. The major outer membrane component lipopolysaccharide
      (LPS) is both an important virulence factor and a major immunogen. Our previous
      studies determined the LPS structures expressed by different P. multocida strains
      and revealed that a number of strains belonging to different serovars contain the
      same LPS biosynthesis locus but express different LPS structures due to mutations
      within glycosyltransferase genes. In this study, we report the full LPS structure
      of the serovar 4 type strain, P1662, and reveal that it shares the same LPS outer
      core biosynthesis locus, L3, with the serovar 3 strains P1059 and Pm70. Using
      directed mutagenesis, the role of each glycosyltransferase gene in LPS outer core
      assembly was determined. LPS structural analysis of 23 Australian field isolates
      that contain the L3 locus revealed that at least six different LPS outer core
      structures can be produced as a result of mutations within the LPS
      glycosyltransferase genes. Moreover, some field isolates produce multiple but
      related LPS glycoforms simultaneously, and three LPS outer core structures are
      remarkably similar to the globo series of vertebrate glycosphingolipids. Our in
      depth analysis showing the genetics and full range of P. multocida
      lipopolysaccharide structures will facilitate the improvement of typing systems
      and the prediction of the protective efficacy of vaccines. 

PMID- 23974033
TI  - The function of the Na+-driven flagellum of Vibrio cholerae is determined by
      osmolality and pH.
AB  - Vibrio cholerae is motile by its polar flagellum, which is driven by a Na(+)
      conducting motor. The stators of the motor, composed of four PomA and two PomB
      subunits, provide access for Na(+) to the torque-generating unit of the motor. To
      characterize the Na(+) pathway formed by the PomAB complex, we studied the
      influence of chloride salts (chaotropic, Na(+), and K(+)) and pH on the motility
      of V. cholerae. Motility decreased at elevated pH but increased if a chaotropic
      chloride salt was added, which rules out a direct Na(+) and H(+) competition in
      the process of binding to the conserved PomB D23 residue. Cells expressing the
      PomB S26A/T or D42N variants lost motility at low Na(+) concentrations but
      regained motility in the presence of 170 mM chloride. Both PomA and PomB were
      modified by N,N'-dicyclohexylcarbodiimide (DCCD), indicating the presence of
      protonated carboxyl groups in the hydrophobic regions of the two proteins. Na(+)
      did not protect PomA and PomB from this modification. Our study shows that both
      osmolality and pH have an influence on the function of the flagellum from V.
      cholerae. We propose that D23, S26, and D42 of PomB are part of an ion-conducting
      pathway formed by the PomAB stator complex. 

PMID- 23974036
TI  - Supportive monitoring and disease management through the internet: an internet
      delivered intervention strategy for recurrent depression.
AB  - Major depression is a highly prevalent, disabling disorder associated with loss
      of quality of life and large economic burden for the society. Depressive
      disorders often follow a chronic or recurrent course. The risk of relapses
      increases with each additional episode. The internet-deliverable intervention
      strategy SUMMIT (SUpportive Monitoring and Disease Management over the InTernet)
      for patients with recurrent depression has been developed with the main
      objectives to prolong symptom-free phases and to shorten symptom-loaden phases.
      This paper describes the study design of a six-sites, three-arm, randomized
      clinical trial intended to evaluate the efficacy of this novel strategy compared
      to treatment as usual (TAU). Two hundred thirty six patients who had been treated
      for their (at least) third depressive episode in one of the six participating
      psychiatric centers were randomized into one of three groups: 1) TAU plus a
      twelve-month SUMMIT program participation with personal support or 2) TAU plus a
      twelve-month SUMMIT program participation without personal support, or 3) TAU
      alone. Primary outcome of this study is defined as the number of "well weeks"
      over 24months after index treatment assessed by blind evaluators based on the
      Longitudinal Interval Follow-Up Evaluation. If efficacious, the low monetary and
      nonmonetary expenditures of this automated, yet individualized intervention may
      open new avenues for providing an acceptable, convenient, and affordable long
      term disease management strategy to people with a chronic mental condition such
      as recurrent depression. 

PMID- 23974034
TI  - Posttranscriptional self-regulation by the Lyme disease bacterium's BpuR DNA/RNA
      binding protein.
AB  - Bacteria require explicit control over their proteomes in order to compete and
      survive in dynamic environments. The Lyme disease spirochete Borrelia burgdorferi
      undergoes substantial protein profile changes during its cycling between vector
      ticks and vertebrate hosts. In an effort to understand regulation of these
      transitions, we recently isolated and functionally characterized the borrelial
      nucleic acid-binding protein BpuR, a PUR domain-containing protein. We now report
      that this regulatory protein governs its own synthesis through direct
      interactions with bpuR mRNA. In vitro and in vivo techniques indicate that BpuR
      binds with high affinity and specificity to the 5' region of its message, thereby
      inhibiting translation. This negative feedback could permit the bacteria to fine
      tune cellular BpuR concentrations. These data add to the understanding of this
      newly described class of prokaryotic DNA- and RNA-binding regulatory proteins. 

PMID- 23974037
TI  - Niobium-based superconducting nano-device fabrication using all-metal suspended
      masks.
AB  - We report a novel method for the fabrication of superconducting nano-devices
      based on niobium. The well-known difficulties of lithographic patterning of high
      quality niobium are overcome by replacing the usual organic resist mask by a
      metallic one. The quality of the fabrication procedure is demonstrated by the
      realization and characterization of long and narrow superconducting lines and
      niobium-gold-niobium proximity SQUIDs. 

PMID- 23974035
TI  - The Cooperative Lifestyle Intervention Program-II (CLIP-II): design and methods.
AB  - A complication of cardiovascular disease (CVD) and the metabolic syndrome (MetS)
      among older adults is loss of mobility. The American Heart Association has
      identified weight management as a core component of secondary prevention programs
      for CVD and is an important risk factor for physical disability. The American
      Society for Nutrition and the Obesity Society have highlighted the need for long
      term randomized clinical trials to evaluate the independent and additive effects
      of diet-induced weight loss (WL) and physical activity in older persons on
      outcomes such as mobility, muscle function, and obesity related diseases. Here we
      describe the rationale, design, and methods of a translational study, the
      Cooperative Lifestyle Intervention Program-II (CLIP-II). CLIP-II will randomize
      252 obese, older adults with CVD or MetS to a weight loss only treatment (WL),
      aerobic exercise training (AT)+WL, or resistance exercise training (RT)+WL for 18
      months. The dual primary outcomes are mobility and knee extensor strength. The
      interventions will be delivered by YMCA community partners with our staff as
      trainers and advisers. This study will provide the first large scale trial to
      evaluate the effects of diet-induced WL on mobility in obese, older adults with
      CVD or MetS as compared to WL combined with two different modes of physical
      activity (AT and RT). Because uncertainty exists about the best approach for
      promoting WL in older adults due to concerns with the loss of lean mass, the
      design also permits a contrast between AT+WL and RT+WL on muscle strength.

PMID- 23974038
TI  - A HCN4+ cardiomyogenic progenitor derived from the first heart field and human
      pluripotent stem cells.
AB  - Most of the mammalian heart is formed from mesodermal progenitors in the first
      and second heart fields (FHF and SHF), whereby the FHF gives rise to the left
      ventricle and parts of the atria and the SHF to the right ventricle, outflow
      tract and parts of the atria. Whereas SHF progenitors have been characterized in
      detail, using specific molecular markers, comprehensive studies on the FHF have
      been hampered by the lack of exclusive markers. Here, we present Hcn4
      (hyperpolarization-activated cyclic nucleotide-gated channel 4) as an FHF marker.
      Lineage-traced Hcn4+/FHF cells delineate FHF-derived structures in the heart and
      primarily contribute to cardiomyogenic cell lineages, thereby identifying an
      early cardiomyogenic progenitor pool. As a surface marker, HCN4 also allowed the
      isolation of cardiomyogenic Hcn4+/FHF progenitors from human embryonic stem
      cells. We conclude that a primary purpose of the FHF is to generate cardiac
      muscle and support the contractile activity of the primitive heart tube, whereas
      SHF-derived progenitors contribute to heart cell lineage diversification. 

PMID- 23974039
TI  - MicroRNA-205 controls neonatal expansion of skin stem cells by modulating the
      PI(3)K pathway.
AB  - Skin stem cells (SCs) are specified and rapidly expanded to fuel body growth
      during early development. However, the molecular mechanisms that govern the
      amplification of skin SCs remain unclear. Here we report an essential role for
      miR-205, one of the most highly expressed microRNAs in skin SCs, in promoting
      neonatal expansion of these cells. Unlike most mammalian miRNAs, genetic deletion
      of miR-205 causes neonatal lethality with severely compromised epidermal and hair
      follicle growth. In the miR-205 knockout skin SCs, phospho-Akt is significantly
      downregulated, and the SCs prematurely exit the cell cycle. In the hair follicle,
      this accelerates the transition of the neonatal SCs towards quiescence. We
      identify multiple miR-205-targeted negative regulators of PI(3)K signalling that
      mediate the repression of phospho-Akt and restrict the proliferation of SCs. Our
      findings reveal an essential role for miR-205 in maintaining the expansion of
      skin SCs by antagonizing negative regulators of PI(3)K signalling. 

PMID- 23974040
TI  - XMAP215 activity sets spindle length by controlling the total mass of spindle
      microtubules.
AB  - Metaphase spindles are microtubule-based structures that use a multitude of
      proteins to modulate their morphology and function. Today, we understand many
      details of microtubule assembly, the role of microtubule-associated proteins, and
      the action of molecular motors. Ultimately, the challenge remains to understand
      how the collective behaviour of these nanometre-scale processes gives rise to a
      properly sized spindle on the micrometre scale. By systematically engineering the
      enzymatic activity of XMAP215, a processive microtubule polymerase, we show that
      Xenopus laevis spindle length increases linearly with microtubule growth
      velocity, whereas other parameters of spindle organization, such as microtubule
      density, lifetime and spindle shape, remain constant. We further show that mass
      balance can be used to link the global property of spindle size to individual
      microtubule dynamic parameters. We propose that spindle length is set by a
      balance of non-uniform nucleation and global microtubule disassembly in a liquid
      crystal-like arrangement of microtubules. 

PMID- 23974041
TI  - Stromal-epithelial crosstalk regulates kidney progenitor cell differentiation.
AB  - Present models suggest that the fate of the kidney epithelial progenitors is
      solely regulated by signals from the adjacent ureteric bud. The bud provides
      signals that regulate the survival, renewal and differentiation of these cells.
      Recent data suggest that Wnt9b, a ureteric-bud-derived factor, is sufficient for
      both progenitor cell renewal and differentiation. How the same molecule induces
      two seemingly contradictory processes is unknown. Here, we show that signals from
      the stromal fibroblasts cooperate with Wnt9b to promote differentiation of the
      progenitors. The atypical cadherin Fat4 encodes at least part of this stromal
      signal. Our data support a model whereby proper kidney size and function is
      regulated by balancing opposing signals from the ureteric bud and stroma to
      promote renewal and differentiation of the nephron progenitors. 

PMID- 23974042
TI  - The role of cyclin D1 in response to long-term exposure to ionizing radiation.
AB  - The health-related hazards resulting from long-term exposure to radiation remain
      unknown. Thus, an appropriate molecular marker is needed to clarify these
      effects. Cyclin D1 regulates the cell cycle transition from the G 1 phase to the
      S phase. Cyclin D1 is degraded as a G1/S checkpoint after 10 Gy of single acute
      radiation exposure, whereas conversely, cyclin D1 is stabilized when human tumor
      cells are exposed to fractionated radiation (FR) with 0.5 Gy of x-rays for 31 d.
      In this article, we review new findings regarding cyclin D1 overexpression in
      response to long-term exposure to FR. Cyclin D1 overexpression is associated with
      induction of genomic instability in irradiated cells. Therefore, repression of
      cyclin D1 expression is likely to cancel the harmful effects of long-term
      exposure to FR. Thus cyclin D1 may be a marker of long-term exposure to radiation
      and is a putative molecular radioprotection target for radiation safety. 

PMID- 23974043
TI  - Effect of high-fat diet prior to pregnancy on hepatic gene expression and
      histology in mouse offspring.
AB  - Maternal overnutrition and obesity are associated with fetal development and
      cause long-term effects in offspring. However, the effects of a high-fat diet
      specific to the pre-pregnancy period are not determined. The present study aimed
      to examine the effect of high-fat diet prior to pregnancy on the liver of mouse
      offspring. Female C57BL/6J mice were fed a normal chow (15.2% fat by energy)
      [control diet (CTR) and CTR pre-pregnancy (PP) groups] or a high-fat chow (31.2%
      fat by energy) [high-fat diet (HFD) and HFD-pre-pregnancy (PP) groups] for 3-4
      weeks and then mated with male C57BL/6J mice fed normal chow. Some mothers
      continued on the same diet until pups reached 21 days of age (CTR and HFD), and
      others were fed the different chows from gestational day 0 (CTR-PP and HFD-PP) to
      determine the effects of a high-fat diet during the pre-pregnancy period in HFD
      PP/CTR and HFD/CTR-PP comparisons. Liver tissues from pups were subjected to gene
      expression analysis by quantitative reverse transcription-polymerase chain
      reaction (RT-PCR) and microarray, and histological analysis using Oil Red O
      staining (Sigma Chemical Co., Ltd., Balcatta, WA, USA). Lipid droplets were
      increased in hepatocytes of mice in HFD-PP compared to CTR and those in HFD
      compared to CTR-PP. Expression of stearoyl-coenzyme A desaturase 1 (Scd1), acetyl
      coenzyme A carboxylase beta (Acacb), and fatty acid binding protein 5 (Fabp5) was
      increased by maternal high-fat diet during pre-pregnancy. The results showed that
      maternal high-fat diet intake prior to pregnancy uniquely affects metabolic
      phenotype related to health and disease in the liver of the next generation.

PMID- 23974044
TI  - Reply to Ruiz-Arguello et al.: Comparison study of two commercially available
      methods for the determination of infliximab, adalimumab, etanercept and anti-drug
      antibody levels.

PMID- 23974045
TI  - Still more discussion on the journal impact factor.

PMID- 23974046
TI  - Nurse educators' perspectives on student development of reflection for
      psychiatric mental health nursing practice.
AB  - Psychiatric nursing, in various parts of the world, including regions of Canada,
      is recognized as a distinct nursing profession. In psychiatric mental health
      nursing practice, reflection is considered a foundational skill given the
      relational nature of nurses' therapeutic work. Communicating the significance of
      reflection for practice to students and teaching this intangible skill is
      challenging for educators. The purpose of this qualitative study was to explore
      with psychiatric mental health nurse educators their views on how they develop
      reflective practitioners. Participants' perspectives and experiences in teaching
      reflective practice were captured in four themes: building the use of self as an
      agent of change, building skills of reflection/building the habit of reflection,
      building a bridge between theory and practice, and building a continuing
      reflective practice - from student to practitioner. Recommendations include a
      systematic incorporation of reflection into a curriculum and creating supportive
      learning environments that facilitate the development of reflective
      practitioners.

PMID- 23974047
TI  - Long-term calorie restriction has minimal impact on brain metabolite and fatty
      acid profiles in aged rats on a Western-style diet.
AB  - The effect of long-term calorie restriction (CR) on metabolites, fatty acid
      profiles and energy substrate transporter expression in the brain was assessed in
      aged rats. Three groups of male Sprague-Dawley rats were studied: (i) a 2 month
      old ad libitum-fed (2AL group), (ii) a 19 month old ad libitum-fed (19AL group),
      and (iii) a 19 month old group subjected to 40% CR from the age of 7.5 to 19
      months (19CR group). The diet contained high sucrose and low n-3 polyunsaturated
      fatty acids (PUFA) so as to imitate a Western-style diet. High resolution magic
      angle spinning-(1)H NMR showed an effect of aging on brain cortex metabolites
      compared to 2AL rats, the largest differences being for myo-inositol (+251% and
      +181%), lactate (+203% and +188%), beta-hydroxybutyrate (+176% and +618%) and
      choline (+148% and +120%), in 19AL and 19 CR rats, respectively. However, brain
      metabolites did not differ between the 19AL and 19CR groups. Cortex fatty acid
      profiles showed that n-3 PUFA were 35-47% lower but monounsaturated fatty acids
      were 40-52% higher in 19AL and 19CR rats compared to 2AL rats. Brain microvessel
      glucose transporter (GLUT1) was 68% higher in 19AL rats than in 2AL rats, while
      the monocarboxylate transporter, MCT1, was 61% lower in 19CR rats compared to
      19AL rats. We conclude that on a high-sucrose, low n-3 PUFA diet, the brain of
      aged AL rats had higher metabolites and microvessel GLUT1 expression compared to
      2AL rats. However, long-term CR in aged rats did not markedly change brain
      metabolite or fatty acid profile, but did reduce brain microvessel MCT1
      expression.

PMID- 23974048
TI  - Etazolate rescues behavioral deficits in chronic unpredictable mild stress model:
      modulation of hypothalamic-pituitary-adrenal axis activity and brain-derived
      neurotrophic factor level.
AB  - Preliminary study in our laboratory showed that etazolate produced antidepressant
      and anxiolytic-like effects in rodent models, however, the ability of etazolate
      to produce antidepressant- and anxiolytic-like effects and underlying
      mechanism(s) in chronic unpredictable mild stress (CUMS) model have not been
      adequately addressed. This study was aimed to investigate the beneficial effects
      of etazolate on CUMS-induced behavioral deficits (depression- and anxiety-like
      behaviors). In addition, the possible underlying mechanism(s) of etazolate in
      CUMS model was also investigated by measuring serum corticosterone (CORT) and
      brain-derived neurotrophic factor (BDNF) levels. Mice were subjected to a battery
      of stressors for 28 days. Etazolate (0.5 and 1 mg/kg, p.o.) and fluoxetine
      (20mg/kg, p.o.) were administered during the last 21 days (8-28th) of the CUMS
      paradigm. The results showed that 4-weeks CUMS produces significant depression
      like behavior in tail suspension test (TST) and partial anxiety-like behavior in
      elevated plus maze (EPM) and open field test (OFT). Stressed mice have also shown
      a significant high serum CORT and low BDNF level. Chronic treatment with
      etazolate (0.5 and 1mg/kg., p.o.) and fluoxetine (20mg/kg., p.o.) produced
      significant antidepressant-like behavior in TST (decreased duration of
      immobility), whereas, partial anxiolytic-like behavior in EPM (increased
      percentage of open arm entries) and OFT (increased % central ambulation score,
      total ambulation score and time spent in center zone). In addition, etazolate and
      fluoxetine treatment significantly (p<0.05) increased the BDNF level and
      inhibited the hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity, as
      evidenced by low serum CORT level in stressed mice. In addition, etazolate and
      fluoxetine also showed significant antidepressant- and anxiolytic-like effects in
      normal control mice. In this study no significant changes were observed in
      locomotor activity in actophotometer test. Moreover, we did not find any effect
      of etazolate and fluoxetine on CORT and BDNF levels in normal control mice. In
      conclusion, the results of the present study suggested compelling evidences that
      etazolate has more marked effect on depression-like behavior in mice, which is
      atleast in part may be related to their modulating effects on the HPA axis and
      BDNF level.

PMID- 23974049
TI  - Cognitive biases explain religious belief, paranormal belief, and belief in
      life's purpose.
AB  - Cognitive theories of religion have postulated several cognitive biases that
      predispose human minds towards religious belief. However, to date, these
      hypotheses have not been tested simultaneously and in relation to each other,
      using an individual difference approach. We used a path model to assess the
      extent to which several interacting cognitive tendencies, namely mentalizing,
      mind body dualism, teleological thinking, and anthropomorphism, as well as
      cultural exposure to religion, predict belief in God, paranormal beliefs and
      belief in life's purpose. Our model, based on two independent samples (N=492 and
      N=920) found that the previously known relationship between mentalizing and
      belief is mediated by individual differences in dualism, and to a lesser extent
      by teleological thinking. Anthropomorphism was unrelated to religious belief, but
      was related to paranormal belief. Cultural exposure to religion (mostly
      Christianity) was negatively related to anthropomorphism, and was unrelated to
      any of the other cognitive tendencies. These patterns were robust for both men
      and women, and across at least two ethnic identifications. The data were most
      consistent with a path model suggesting that mentalizing comes first, which leads
      to dualism and teleology, which in turn lead to religious, paranormal, and life's
      purpose beliefs. Alternative theoretical models were tested but did not find
      empirical support. 

PMID- 23974050
TI  - Association between human leukocyte antigen class I and II alleles and hepatitis
      C virus infection in high-risk hemodialysis patients awaiting kidney
      transplantation.
AB  - Recent evidences have shown that several host genetic factors influence
      susceptibility or protection to hepatitis C virus (HCV) infection. There are
      controversial data regarding the associations of human leukocyte antigens (HLA)
      and the clearance or progression of HCV. The aim of this study was to investigate
      whether particular HLA molecules were associated with HCV infection in recipients
      awaiting kidney transplantation considered at high-risk to infection due to
      protracted hemodialysis treatment. To this purpose, 301 kidney recipients with
      HCV infection and 1103 uninfected recipients were examined for HLA class I and II
      molecules. In our case-control study, HLA-A(*)26 is positively associated with
      HCV infection while HLA-A(*)29, -B(*)40 and -DRB1(*)01 are negatively associated
      with HCV infection. Multiple logistic regression analysis demonstrated that age
      (OR = 1.02; 95% CI = 1.01-1.04; p < 0.00), HLA-A(*)26, -A(*)29, -B(*)40 and 
      DRB1(*)01 [(OR = 1.54; 95% CI = 1.03-2.30; p = 0.03); (OR = 0.50; 95% CI = 0.26
      0.99; p = 0.05); (OR = 0.42; 95% CI = 0.23-0, 7; p = 0.01); (OR = 0.62; 95% CI =
      0.41-0, 94; p = 0.03); respectively] are independent predictors of HCV infection.
      Our results suggest that particular HLA molecules, as host genetic factors, may
      have a relationship with susceptibility or protection to HCV infection also in
      recipients awaiting kidney transplantation.

PMID- 23974051
TI  - TLR-9 promoter polymorphisms (T-1237C and T-1486C) are not associated with
      systemic lupus erythematosus: a case control study and meta-analysis.
AB  - Toll like receptors (TLRs) are essential molecules implicated in both innate and
      adaptive immune response. Polymorphisms in TLR gene have been associated with
      various infectious diseases and autoimmune disorders. Role of TLR9 has been
      elegantly demonstrated in both human systemic lupus erythematosus (SLE) and mice
      model of lupus. In the present study we investigated association of TLR-9
      promoter polymorphisms (T-1237C and T-1486C) with susceptibility/resistance to
      SLE in an Eastern Indian state which is endemic to parasitic diseases. 210 Female
      SLE patients who fulfilled the American College of Rheumatology criteria were
      enrolled along with matched healthy controls from Odisha, India. TLR-9
      polymorphisms (T-1237C and T-1486C) were typed by polymerase chain reaction
      followed by restriction fragment length polymorphism. For meta-analysis, relevant
      literatures were searched from PubMed database and comprehensive meta-analysis V2
      software was employed for analysis. Allele and genotype frequency of TLR-9
      promoter polymorphisms (T-1237C and T-1486C) were comparable among SLE patients
      and controls. Further, meta-analysis of earlier reports and present study did not
      reveal a significant association of TLR-9 (T-1237C and T-1486C) polymorphisms
      with SLE. Data from the present study suggest that TLR-9 promoter polymorphisms
      are not associated with susceptibility to SLE in an area endemic to parasitic
      diseases. 

PMID- 23974052
TI  - Leishmania donovani: influence of anti-leishmanial therapy on expression of
      lymphocyte function-associated antigen-3 and its relevance to pathogenisis in
      visceral leishmaniasis.
AB  - Lymphocyte function associated antigen 3 (LFA-3) is known as adhesion molecule
      with its role in T-cell activation signaling as well as in Foxp3 expression. Its
      influences on IL-10 production is also available, whose role in pathogenesis is
      well documented. However, this molecule is not yet directly addressed for its
      association with visceral leishmaniasis (VL). We investigated the relationship
      between Leishmania donovani infection and expression of LFA-3 in VL patients in
      their pre and post treatment stage through this case control study. Present study
      reports L. donovani mediated expression of LFA-3 on CD14(+) monocytes in human
      VL. Active cases of VL was observed with 2.91-fold increased mean florescence
      intensity (MFI) of LFA-3 expression on CD14(+) cells compared to healthy control
      (p = 0.0001). This increased MFI of untreated VL cases was reduced 1.92-fold in
      successfully treated cases (p = 0.0001). This observation was also accorded by
      mRNA expression for LFA-3 in monocytes of corresponding samples. The expression
      of LFA-3 was also observed influenced by L. donovani load in splenic aspirates,
      as it was 1.71-fold elevated in patients with Ld grade >=3+ compared to patients
      with <=2+ Ld grade (p = 0.0121). To evaluate the possibility that L. donovani
      utilize LFA-3 mediated evasion pathway in human visceral leishmaniasis; in vitro
      experiments were performed for measurement of pathogenic cytokine IL-10 and Foxp3
      mRNA expression. The IL-10 production and Foxp3 expression in peripheral blood
      mononuclear cells from VL subjects were observed regulated significantly (p =
      0.0131 and 0.0436 when compared with untreated samples) in presence of an
      antagonist to LFA-3. This study recommends further investigations to strengthen
      the pathogenic and prognostic significance of LFA-3 in visceral leishmaniasis.

PMID- 23974053
TI  - Absence of strong linkage disequilibrium between odorant receptor alleles and the
      major histocompatibility complex.
AB  - The odorant receptor (OR) genes constitute the largest gene family among
      vertebrates. While over 800 loci are present in the human genome, their allele
      diversity is still poorly characterized. It has been hypothesized that the
      products of OR genes can be relevant in the reproductive context, thereby
      interacting with products of genes of the major histocompatibility complex (MHC).
      Here we investigated the genetic diversity of the OR2W6P, OR2B8P, OR1F12 and
      OR12D2 genes, in order to define haplotypes and haplotype frequencies. We
      measured levels of linkage disequilibrium (LD) between these OR genes and the MHC
      genes HLA-A, HLA-B and HLA-DRB1. This was accomplished through the assessment of
      30 single nucleotide polymorphisms (SNPs) in samples from 61 family trios. We
      characterized 26 alleles among the four OR genes and identified three SNPs that
      had not yet been reported. Based on our haplotype analysis, LD spanning the OR
      HLA region is not very strong, and therefore not enough to enable selection
      regarding specific HLA-OR haplotypes. 

PMID- 23974054
TI  - Altered Th17 cells and Th17/regulatory T-cell ratios indicate the subsequent
      conversion from undifferentiated connective tissue disease to definitive systemic
      autoimmune disorders.
AB  - A shift in the balance between Th17-cells and regulatory T-cells (Treg) is an
      important feature of systemic autoimmune diseases (SAID), and may also contribute
      to their development. Hereby, we assessed the distribution of peripheral Th17 and
      Treg-cells in patients with undifferentiated connective tissue disease (UCTD),
      the forerunner of SAIDs and followed these parameters during the development
      towards definitive SAIDs. Fifty-one UCTD patients were investigated and followed
      up for 3 years. Flow cytometry was used to identify and follow three cell
      populations: Th17-cells (CD4+IL-17+ T-cells), natural regulatory T-cells
      (CD4(+)CD25(bright)FoxP3(+); nTregs) and IL-10 producing Type-1 regulatory T
      cells (CD4+IL-10+ T-cells; Tr1). Altogether 37.3% of these patients progressed
      into SAIDs. Th17-cells were increased in UCTD vs. controls, which further
      increased in those, whom developed SAIDs eventually. The Th17/nTreg ratio
      gradually increased from controls through UCTD patients, reaching the highest
      values in SAID-progressed patients. Regarding the Th17/Tr1 ratios, a similar
      tendency was observed moreover Th17/Tr1 could distinguish between UCTD patients
      with, or without subsequent SAID progression in a very early UCTD stage. Various
      immunoserological markers showed association with Th17 and Th17/nTreg at
      baseline, indicating the consecutive development of a distinct SAID. The derailed
      Th17/Treg balance may contribute to disease progression therefore could function
      as a prognostic marker.

PMID- 23974055
TI  - Profile of human leukocyte antigen class I alleles in patients with dengue
      infection from Western India.
AB  - Human leukocyte antigen (HLA) class I alleles are known to affect the cytotoxic T
      lymphocyte responses and influence susceptibility to viral infections. The
      objective of the present study was to find out whether HLA class I alleles are
      associated with clinical manifestations of dengue virus infection. The profile of
      HLA class I alleles were investigated in 224 human subjects [85 dengue fever (DF)
      cases, 29 dengue hemorrhagic fever (DHF) cases and 110 healthy controls (HCs)]
      from Western India using PCR based methods. Results revealed significantly higher
      frequency of HLA-A(*)33 in DF cases compared to HCs [P = 0.032, Odds ratio (OR)
      2.12]. The frequency of HLA-A(*)02:11 was higher in DHF cases compared to DF
      cases. The frequency of HLA-B(*)18 was significantly higher in dengue (DEN) cases
      [P = 0.047 Pc = 0.846, OR 3.53]. The frequency of HLA-Cw(*)07 allele was
      significantly higher in DEN cases [DEN vs. HCs: P = 0.0120, Pc = 0.168, OR 2.00].
      Significance was observed even when the cases were categorized in to DF and DHF
      [DF vs. HCs: P = 0.0349, Pc = 0.49, OR 1.87; DHF vs. HCs: P = 0.0399, Pc = 0.56,
      OR 2.4]. The combined frequency of HLA-Cw(*)07 with HLA-DRB1(*)07/(*)15 genotype
      was significantly higher in DHF cases as compared to DF and HCs [DHF vs. HCs: P =
      0.022, OR 5.31; DHF vs. DF: P = 0.027, OR 5.49]. On the other hand, the frequency
      of combination of HLA-Cw(*)07 without HLA-DRB1(*)07 was significantly higher in
      DF cases compared to HCs [DF vs. HCs: P = 0.002, OR 2.42 (1.28-4.55)]. The
      results suggest that HLA-A(**)33 may be associated with DF while HLA-B(*)18 and
      HLA-Cw(*)07 alleles may be associated with symptomatic dengue requiring
      hospitalization. In the presence of HLA-DRB1(*)07/(*)15 genotype, HLA-Cw(*)07 is
      associated with increased risk of developing DHF while in the presence of other
      HLA-DRB1 alleles, HLA-Cw(*)07 is associated with DF.

PMID- 23974056
TI  - The delivery of renal replacement therapy in Scotland--why the geographic
      variation?
AB  - BACKGROUND: The incidence of patients starting renal replacement therapy (RRT)
      for established renal failure (ERF) in Scotland has fallen from 2005 to 2011 due
      to a reduction in older patients starting RRT; there are significant differences
      between NHS Health board areas. AIM: To understand the apparent inequality in
      provision of RRT between NHS board areas in Scotland. DESIGN: Retrospective
      population analysis of Scottish renal registry (SRR) data, population statistics
      and quality outcomes framework summary statistics. RESULTS: The incidence of
      patients starting RRT for ERF in Scotland fell from 123 per million population
      (pmp) in 2005 to 96 pmp in 2011. The incidence of >=75 year olds fell from 406 to
      274 pmp. There are significant differences between NHS board areas when
      standardized for age and social deprivation. There is no relationship between the
      population prevalence of CKD as reported by QOF and the incidence of RRT for ERF.
      Those areas with high incidence rates of >=75 year olds have higher 90-day
      [Spearman's rank correlation: coefficient = 0.662; P = 0.03] and 1-year
      [Spearman's rank correlation: coefficient = 0.776; P = 0.003] mortality rates.
      CONCLUSION: The significant variation in provision of RRT for ERF between
      Scottish NHS Board areas is not explained by age or social deprivation. There is
      evidence of change in practice towards RRT for patients aged >=75 years but
      variation between NHS Board areas. This disparity must be further investigated to
      ensure equity of access to RRT for those who will benefit from it, and to non
      dialytic care for those who would not.

PMID- 23974057
TI  - Temporal variation of methane flux from Xiangxi Bay of the Three Gorges
      Reservoir.
AB  - Three diel field campaigns and one monthly sampling campaign during June 2010-May
      2011 were carried out to investigate the CH4 flux across the water-gas interface
      in Xiangxi Bay of the Three Gorges Reservoir, China. The average CH4 flux was
      much less than that reported from reservoirs in tropic and temperate regions. The
      photosynthesis of phytoplankton dominated the diel gas fluxes during alga bloom
      in spring and summer. The maximum monthly flux occurred in June 2010 and
      corresponded to the lowest water level. Water temperature, sediment temperature,
      and TOC did not have significant correlation with the monthly CH4 fluxes.
      Continuously decreasing hydrostatic pressure and the low water level resulted in
      more CH4 emission at the sediment-water during the discharging period, and thus
      increases the CH4 effluxes because the diffusion time through a thin water column
      is shorter and less CH4 may be oxidized compared with that in a long water
      column. 

PMID- 23974058
TI  - Inflammatory myofibroblastic tumor of the liver in children.
AB  - Inflammatory pseudotumors, now more aptly termed inflammatory myofibroblastic
      tumors (IMTs), are uncommon benign neoplasms, which have been reported in most
      organs and tissues in the body. Originally described and commonly found in the
      lung, they are also found in the liver of children and adults. We review the
      literature and analyze the features of the hepatic IMTs reported in children,
      along with a case report of a 15-month-old boy who had a persistent IMT in the
      liver and underwent surgical resection for the same following a trial of
      conservative management. 

PMID- 23974059
TI  - Cow's milk-associated gastrointestinal symptoms evaluated using the double-blind,
      placebo-controlled food challenge.
AB  - OBJECTIVE: The aim of this study was to evaluate the suspicion of cow's-milk
      allergy in infants with unspecific gastrointestinal (GI) symptoms using the
      double-blind, placebo-controlled food challenge. METHODS: A prospective cohort
      study, which recruited 57 consecutive children with gastrointestinally manifested
      symptoms suspected of cow's-milk allergy. All patients underwent a 5-day double
      blind, placebo-controlled food challenge for cow's milk. RESULTS: The median age
      of the patients was 8.7 months. None had measurable cow's-milk-specific IgE. The
      food challenge was positive in 18 (32%) cases, with symptoms manifesting within
      48 hours in 17 of 18 cases. The only symptom that correlated with the positive
      challenge was loose stools, reported as a presenting symptom in 78% of challenge
      positive and in 46% of challenge-negative children (P = 0.043). During active
      challenge, the respective proportions were 82% and 2% (P < 0.0001). No serious
      adverse effects were manifested during the challenges. In the challenge-negative
      group, significant placebo reactions occurred in 18 (46%) patients. In the
      challenge-negative children, adult-type hypolactasia genotype CC frequency was
      higher (31%, P = 0.033) than national prevalence of 18%. CONCLUSIONS: In an
      infant with unspecific GI symptoms suspected of cow's-milk allergy, this
      diagnosis is seldom confirmed. Other reasons for the troublesome GI symptoms
      should also be identified.

PMID- 23974061
TI  - Endoscopic and histologic analysis of gastric mucosa-associated lymphoid tissue
      in children with Helicobacter pylori infection.
AB  - OBJECTIVES: Nodular gastritis (NG) associated with Helicobacter pylori infection
      can occur commonly in childhood and is regarded to be benign without clinical
      significance. This study includes endoscopic and histologic analysis of gastric
      mucosa-associated lymphoid tissue (MALT) to clarify the significance of NG on
      endoscopy in H pylori-infected children. METHODS: Of the 758 children who
      underwent endoscopy, 80 were identified as having H pylori infection. These
      patients were divided into 3 groups based on endoscopic severity of gastric
      nodularity. Histopathologic grading of MALT and immunohistochemistry of CD3,
      CD20, cytokeratin, and Ki-67 were evaluated. RESULTS: On endoscopy, severe NG was
      observed in the antrum of 38 of the 80 subjects, mild NG in 27, and an absence of
      NG in 15. Density of H pylori and lymphocyte infiltration differed among the 3
      groups (P=0.022 and P=0.025, respectively). Histological grading for gastric
      lymphoid infiltrates was compatible with grade 1 in 47 (58.8%), grade 2 in 21
      (26.3%), grade 3 in 7 (8.8%), and grade 4-5 in 4 (5.1%) in the antrum. Degree of
      NG, density of H pylori, neutrophil activity, and gastritis score in the antrum
      varied with MALT grades (P=0.003, P=0.042, P=0.028, and P=0.006, respectively).
      CONCLUSIONS: Our study suggests NG may present as a significant gastric
      manifestation of childhood H pylori infection that indicates gastric MALT.
      Thorough histologic investigation may be useful in the evaluation of gastric MALT
      in children infected with H pylori that manifests as severe NG in the antrum.

PMID- 23974060
TI  - Interleukin-17 immunity in pediatric Crohn disease and ulcerative colitis.
AB  - OBJECTIVE: The present understanding of inflammatory bowel disease pathogenesis
      mainly relies on studies of adult patients. Therefore, we studied the balance
      between T-effector and regulatory cells in pediatric inflammatory bowel disease.
      METHODS: Quantitative polymerase chain reaction and immunohistochemistry served
      to quantify the expression of immunological markers in mucosal biopsies and flow
      cytometry analysis was used in peripheral blood mononuclear cells. RESULTS:
      Colonic interleukin (IL)-17+, IL-22, and IL-6 mRNA upregulation and increase in
      the number of colonic IL-17 cells were demonstrated in both Crohn disease (CD)
      and ulcerative colitis (UC). Likewise, colonic forkhead box P3 (FOXP3+) mRNA
      expression and the number of colonic FOXP3 cells were increased both in CD and in
      UC and were accompanied in CD also with increased numbers of FOXP3+CD25 High CD4
      cells in peripheral blood. Ileal relation of IL-17/CD4 cells was increased only
      in CD. CONCLUSIONS: We showed activation of colonic IL-17/IL-22 axis and
      upregulation of FOXP3 to occur both in pediatric CD and in UC, indicating shared
      immunological characteristics. Upregulation of IL-17 was restricted to colon in
      UC, but existed in the ileum and in the colon in active CD.

PMID- 23974062
TI  - Effectiveness of trimethoprim-sulfamethoxazole and metronidazole in the treatment
      of small intestinal bacterial overgrowth in children living in a slum.
AB  - Trimethoprim-sulfamethoxazole and metronidazole were used for 14 days to treat 20
      children with small intestine bacterial overgrowth (SIBO). SIBO was diagnosed
      using the lactulose hydrogen breath test. The breath test was repeated 1 month
      after treatment, and 19 (95.0%) of 20 children showed no evidence of SIBO (P <
      0.001). The area under the individual curves showed that children with SIBO
      exhibited greater hydrogen production before treatment in both the first hour and
      between 60 and 180 minutes after the breath test. The treatment did not decrease
      methane production. In conclusion, trimethoprim-sulfamethoxazole and
      metronidazole was effective in treating children with SIBO.

PMID- 23974063
TI  - Diagnosis and treatment of perianal Crohn disease: NASPGHAN clinical report and
      consensus statement.
AB  - Inflammatory bowel disease is a chronic inflammatory disorder of the
      gastrointestinal tract that includes both Crohn disease (CD) and ulcerative
      colitis. Abdominal pain, rectal bleeding, diarrhea, and weight loss characterize
      both CD and ulcerative colitis. The incidence of IBD in the United States is 70
      to 150 cases per 100,000 individuals and, as with other autoimmune diseases, is
      on the rise. CD can affect any part of the gastrointestinal tract from the mouth
      to the anus and frequently will include perianal disease. The first description
      connecting regional enteritis with perianal disease was by Bissell et al in 1934,
      and since that time perianal disease has become a recognized entity and an
      important consideration in the diagnosis and treatment of CD. Perianal Crohn
      disease (PCD) is defined as inflammation at or near the anus, including tags,
      fissures, fistulae, abscesses, or stenosis. The symptoms of PCD include pain,
      itching, bleeding, purulent discharge, and incontinence of stool. In this report,
      we review and discuss the etiology, diagnosis, evaluation, and treatment of PCD. 

PMID- 23974064
TI  - A new genetic mutation in a patient with syndromic diarrhea and hepatoblastoma.

PMID- 23974065
TI  - 2013 update on celiac disease and eosinophilic esophagitis.
AB  - Celiac disease is a chronic, immune-mediated disorder, characterized by small
      intestinal inflammation and villous atrophy after the ingestion of gluten by
      genetically susceptible individuals. Several extraintestinal manifestations have
      been associated to celiac disease. Eosinophilic esophagitis is a primary disorder
      of the esophagus characterized by upper gastrointestinal symptoms, absence of
      gastroesophageal reflux disease and more than 15 eosinophils per high-power field
      in biopsy specimens. Both celiac disease and eosinophilic esophagitis are caused
      by aberrant, but distinct, immune responses to ingested antigens and can be
      responsive to restricted food intake. The aim of this review is to assess whether
      there is an association between these two pathologies. In the majority of the
      studies examined, including the studies in pediatric population, the prevalence
      of eosinophilic esophagitis in subjects with celiac disease was about 10-times
      that of the general population. We suggest searching for eosinophilic esophagitis
      in all children undergoing endoscopy for suspicious celiac disease. 

PMID- 23974066
TI  - Reactions of dimethylzirconocene complexes with a vicinal frustrated P/B Lewis
      pair.
AB  - The intramolecular vicinal frustrated P/B Lewis pair (FLP) Mes2PCH2CH2B(C6F5)2
      readily abstracts a methyl anion equivalent from dimethylzirconocene to give the
      salt [Cp2ZrCH3](+) [Mes2PCH2CH2B(CH3)(C6F5)2](-) that features phosphane
      coordination to the zirconium cation. The analogous reaction between this FLP and
      Cp*2Zr(CH3)2 yields the analogous salt that, however, features a methyl bridged
      ([Zr]...H3C-[B]) tight ion pair structure. Both these products were characterized
      by X-ray diffraction. They both undergo 1,2-[Zr(+)]/P addition to carbon dioxide.
      The [Cp2ZrCH3](+) containing compound also adds to benzaldehyde or to p-tolyl
      isocyanate to give the respective [Zr(+)]/P addition products which were
      characterized by X-ray diffraction.

PMID- 23974067
TI  - Human pregnane X receptor: a novel target for anticancer drug development.
AB  - Multidrug resistance (MDR), a significant barrier to effective pharmacokinetics
      and pharmacodynamics of anticancer drugs, is mainly due to the induction
      potential of anticancer drugs for drug metabolizing enzymes (DMEs) and efflux
      transporters through nuclear receptors. Human Pregnane X Receptor (hPXR) is
      master transcription factor for cytochrome P450 3A4 (CYP3A4) and multidrug
      resistance protein 1 (MDR1). The hPXR is capable of being activated by
      structurally diverse ligands. Several studies, like in silico modeling, in vitro
      assays, and in vivo experimentation have been conducted to identify the
      structural features of ligand for activation of hPXR. This review highlights hPXR
      as an appealing target for both the development of novel anticancer drugs and the
      improvement in preclinical and clinical evaluation of anticancer drugs. 

PMID- 23974068
TI  - Strategies and validation for siRNA-based therapeutics for the reversal of multi
      drug resistance in cancer.
AB  - Resistance of cancer cells to anticancer drugs is the main reason for the failure
      of traditional cancer treatments. Various cellular components and different loops
      within the signaling pathways contribute to drug resistance which could be
      modulated with the aim to restore drug efficacy. Unveiling the molecular
      mechanisms for cancer drug resistance has now paved the way for the development
      of novel approaches to regulate the response rates to anticancer drugs at the
      genetic level. The recent progress on identification and validation of the vital
      genes directly or indirectly involved in development of cancer drug resistance
      with the aid of the specific knock down ability of RNA interference technology is
      discussed in this review. 

PMID- 23974069
TI  - Is bisphosphonate therapy compromised by the emergence of adverse bone disorders?
AB  - Bisphosphonates (BPs) are the preferred class of antiresorptive agents used for
      the treatment of osteoporosis and bone metastases. Recently, an increasing number
      of clinical reports concerning osteonecrosis of the jaw and atypical fractures
      have suggested a link between prolonged use of BPs and these adverse bone events,
      which are exceptionally difficult to treat. Even though these side effects were
      mainly observed in patients with metastases, osteoporotic patients might become
      increasingly affected by these conditions with the increasing use of injectable
      BPs. Could these severe adverse bone events compromise the use of BPs? The
      development of these unfavorable conditions as a consequence of oversuppression
      of bone resorption could raise concern regarding the use of therapeutic
      strategies involving antiresorptive drugs. 

PMID- 23974070
TI  - Zebrafish as a model to study PTPs during development.
AB  - Protein-tyrosine phosphatases (PTPs) have important roles in signaling, but
      relatively little is known about their function in vivo. We are using the
      zebrafish as a model to study the function of PTPs at the organismal, cellular
      and molecular level. The zebrafish is an excellent experimental model for the
      analysis of gene function. We have developed methods to quantitatively study
      effects of PTP knockdown or expression of (mutant) PTPs, particularly with
      respect to gastrulation cell movements. Moreover, we have studied the
      phosphoproteome of zebrafish embryos. In this review, we will discuss methods to
      manipulate the zebrafish genome and techniques that we have developed to assess
      developmental defects during gastrulation and to assess differences in the
      phosphoproteome. 

PMID- 23974071
TI  - Systematical identification of splicing regulatory cis-elements and cognate trans
      factors.
AB  - The majority of human genes undergo alternative splicing to generate multiple
      isoforms with distinct functions. This process is generally controlled by cis
      acting splicing regulatory elements (SREs) that recruit trans-acting factors to
      promote or inhibit the use of nearby splice sites. The growing interest in
      understanding the regulatory rules of splicing necessitates the systematic
      identification of these SREs and their cognate protein factors using experimental
      and computational approaches. Here we describe a strategy to identify and analyze
      both cis-acting SREs and trans-acting splicing factors. This strategy involves a
      cell-based screen to identify SREs from a random sequences library and a modified
      RNA affinity purification approach to unbiasedly identify the splicing factors.
      These methods can be adopted to identify splicing enhancers or silencers in both
      exons and introns, and can be extended to different cultured cells. The resulting
      SREs and splicing factors can be further analyzed with a series of computational
      and experimental approaches. This approach will help us to collect a molecular
      part-list for splicing regulation, providing a rich data source that enables a
      better understanding of the "splicing code". 

PMID- 23974072
TI  - Binding and isolation of tumor cells in biological media with perfluorocarbon
      microbubbles.
AB  - With the emerging interest in personalized medicine, there is strong demand for
      new technologies for clinical sample interrogation. Exfoliated tumor cells in
      variety of pathological samples (e.g., blood, bone marrow, urine) could provide
      invaluable information for diagnosis and prognosis of cancers. Here we describe a
      detailed method for capture and isolation of tumor cells in medium, blood, or
      large issue buffy coat using EpCAM-targeted buoyant microbubbles (MBs).
      Perflorohexane gas lipid shell MBs were prepared with emulsification method and
      conjugated with antibody as described by us before [25]. The binding of EpCAM
      targeted MBs to A549 (human lung carcinoma) and 4T1 (mouse breast carcinoma)
      cells spiked into BSA/PBS or blood was more than 90%, which was comparable with
      commercial anti-EpCAM immunomagnetic beads (DynaBeads). Anti-EpCAM MBs
      efficiently (75-82%) isolated BxPC3 pancreatic tumor cells spiked into medium,
      blood or a buffy coat, within 15-30 min of incubation. We discuss MB parameters
      and experimental conditions critical to achieve efficient cells binding and
      isolation. In conclusion, MB-assisted cell isolation is a promising method for
      rapid enrichment of cells and biomarkers from biological samples.

PMID- 23974074
TI  - Particle size distribution of radioactive aerosols after the Fukushima and the
      Chernobyl accidents.
AB  - Following the Fukushima accident, a series of aerosol samples were taken between
      24th March and 13th April 2011 by cascade impactors in the Czech Republic to
      obtain the size distribution of (131)I, (134)Cs, (137)Cs, and (7)Be aerosols. All
      distributions could be considered monomodal. The arithmetic means of the activity
      median aerodynamic diameters (AMADs) for artificial radionuclides and for (7)Be
      were 0.43 and 0.41 MUm with GDSs 3.6 and 3.0, respectively. The time course of
      the AMADs of (134)Cs, (137)Cs and (7)Be in the sampled period showed a slight
      decrease at a significance level of 0.05, whereas the AMAD pertaining to (131)I
      increased at a significance level of 0.1. Results obtained after the Fukushima
      accident were compared with results obtained after the Chernobyl accident. The
      radionuclides released during the Chernobyl accident for which we determined the
      AMAD fell into two categories: refractory radionuclides ((140)Ba, (140)La
      (141)Ce, (144)Ce, (95)Zr and (95)Nb) and volatile radionuclides ((134)Cs,
      (137)Cs, (103)Ru, (106)Ru, (131)I, and (132)Te). The AMAD of the refractory
      radionuclides was approximately 3 times higher than the AMAD of the volatile
      radionuclides; nevertheless, the size distributions for volatile radionuclides
      having a mean AMAD value of 0.51 MUm were very close to the distributions after
      the Fukushima accident.

PMID- 23974073
TI  - The beta-sliding clamp directs the localization of HdaA to the replisome in
      Caulobacter crescentus.
AB  - The initiation of chromosome replication is tightly regulated in bacteria to
      ensure that it takes place only once per cell cycle. In many proteobacteria, this
      process requires the ATP-bound form of the DnaA protein. The regulatory
      inactivation of DnaA (RIDA) facilitates the conversion of DnaA-ATP into
      replication-inactive DnaA-ADP, thereby preventing overinitiation. Homologues of
      the HdaA protein, together with the beta-clamp of the DNA polymerase (DnaN), are
      required for this process. Here, we used fluorescence resonance energy transfer
      experiments to demonstrate that HdaA interacts with DnaN in live Caulobacter
      crescentus cells. We show that a QFKLPL motif in the N-terminal region of HdaA is
      required for this interaction and that this motif is also needed to recruit HdaA
      to the subcellular location occupied by the replisome during DNA replication. An
      HdaA mutant protein that cannot colocalize or interact with DnaN can also not
      support the essential function of HdaA. These results suggest that the
      recruitment of HdaA to the replisome is needed during RIDA in C. crescentus,
      probably as a means to sense whether chromosome replication has initiated before
      DnaA becomes inactivated. In addition, we show that a conserved R145 residue
      located in the AAA+ domain of HdaA is also needed for the function of HdaA,
      although it does not affect the interaction of HdaA with DnaN in vivo. The AAA+
      domain of HdaA may therefore be required during RIDA after the initial
      recruitment of HdaA to the replisome by DnaN. 

PMID- 23974075
TI  - Geographical trends in 137Cs fallout from the Chernobyl accident and leaching
      from natural surface soil in Norway.
AB  - In order to follow the turnover of (137)Cs in natural soils and estimate future
      trends in exposure of livestock, samples of natural surface soils were collected
      at 0-3 cm depth at 464 sites in 1995 and 463 sites in 2005 covering the country.
      In both cases the geographical pattern observed was similar to the original
      distribution from 1986, but the decline of (137)Cs activity in the surface soil
      was not the same everywhere. In 1995 the (137)Cs reduction since 1986 was found
      to be considerably greater in coastal areas than farther inland. The main reason
      for this appears to be the much greater deposition of marine cations such as
      Mg(2+) and Na(+) in the coastal areas, replacing Cs ions fixed on soil particle
      surfaces. This cation exchange appeared to be particularly strong near the
      southern coast where deposition of NH4(+) from transboundary air pollution is
      evident in addition to the marine cations. During 1995-2005 the (137)Cs decline
      in the surface soil was more uniform over the country than in the preceding 10
      year period but still significantly higher in coastal areas than inland.
      Differences in precipitation chemistry may have influenced the uptake of (137)Cs
      in terrestrial food chains.

PMID- 23974076
TI  - Radon emanation from low-grade uranium ore.
AB  - Estimation of radon emanation in uranium mines is given top priority to minimize
      the risk of inhalation exposure due to short-lived radon progeny. This paper
      describes the radon emanation studies conducted in the laboratory as well as
      inside an operating underground uranium mine at Jaduguda, India. Some of the
      important parameters, such as grade/(226)Ra activity, moisture content, bulk
      density, porosity and emanation fraction of ore, governing the migration of radon
      through the ore were determined. Emanation from the ore samples in terms of
      emanation rate and emanation fraction was measured in the laboratory under
      airtight condition in glass jar. The in situ radon emanation rate inside the mine
      was measured from drill holes made in the ore body. The in situ(222)Rn emanation
      rate from the mine walls varied in the range of 0.22-51.84 * 10(-3) Bq m(-2) s(
      1) with the geometric mean of 8.68 * 10(-3) Bq m(-2) s(-1). A significant
      positive linear correlation (r = 0.99, p < 0.001) between in situ(222)Rn
      emanation rate and the ore grade was observed. The emanation fraction of the ore
      samples, which varied in the range of 0.004-0.089 with mean value of 0.025 +/-
      0.02, showed poor correlation with ore grade and porosity. Empirical
      relationships between radon emanation rate and the ore grade/(226)Ra were also
      established for quick prediction of radon emanation rate from the ore body.

PMID- 23974078
TI  - Staphylococcus aureus in veterinary medicine.
AB  - Staphylococcus aureus is a major opportunistic pathogen in humans and one of the
      most important pathogenic Staphylococcus species in veterinary medicine. S.
      aureus is dangerous because of its deleterious effects on animal health and its
      potential for transmission from animals to humans and vice-versa. It thus has a
      huge impact on animal health and welfare and causes major economic losses in
      livestock production. Increasing attention is therefore being paid to both
      livestock and companion animals in terms of this pathogen. In this review, we
      summarise the current knowledge on the animal host adaptation of S. aureus.
      Different types of S. aureus infections in animals are also presented, with
      particular emphasis on mastitis in dairy herds, which is probably the costliest
      and therefore the best documented S. aureus infection seen in animals. 

PMID- 23974079
TI  - Age-related loss of responsiveness to 2,5-dimethoxy-4-iodoamphetamine in liver
      sinusoidal endothelial cells.
AB  - Age-related pseudocapillarization of the liver sinusoidal endothelium is
      associated with impaired lipid and drug metabolism and the development of
      disease. 2,5-Dimethoxy-4-iodoamphetamine is a serotonin receptor 2 agonist that
      has been shown to have beneficial effects on the liver sinusoidal endothelium in
      the setting of partial hepatectomy. Here, we have assessed whether 2,5-dimethoxy
      4-iodoamphetamine influences ultrastructure of the sinusoidal endothelium in
      normal 7- and 24-month-old C57Bl6 mice. Following 48 hours of 2,5-dimethoxy-4
      iodoamphetamine administration, we found that the liver endothelium in the young,
      but not in the old, mice had increased porosity compared with controls. This
      effect appeared to be modulated by increased fenestration size rather than a
      change in fenestration number. 2,5-Dimethoxy-4-iodoamphetamine is a useful
      manipulator of fenestration size in the young liver and could be harnessed in the
      search for therapeutic interventions for pseudocapillarization. 

PMID- 23974080
TI  - Skeletal aging: from bench to bed side.

PMID- 23974081
TI  - Testosterone supplementation improves anemia in aging male mice.
AB  - Whether aging alone causes anemia is still controversial. In this study, we show
      that 28-month-old male C57BL/6 mice, maintained in a pathogen-free environment,
      had significantly lower hemoglobin, hematocrit, and erythrocyte counts than young
      mice. The anemic condition aggravated further from 28 to 30 months. Old mice
      displayed increased erythropoietic activity, evidenced by an increase in
      reticulocyte counts, serum erythropoietin, and splenic expression of
      erythropoietic genes. An increase in late-stage erythroid progenitors was
      detected in spleen but not in bone marrow of the old mice. However, old mice also
      had lower serum iron and transferrin saturation, as well as lower erythrocyte
      iron incorporation rate. Testosterone supplementation restored serum iron status
      in old mice to levels similar to that of young adults, further upregulated
      splenic expression of erythropoietic genes, increased splenic erythroid
      progenitors, and significantly improved the red cell index. In conclusion, we
      found that mice can become anemic at very old age without apparent illness. The
      endogenous compensatory erythropoietic activity was insufficient to normalize the
      red cell index in old mice, either due to impaired iron homeostasis, ineffective
      erythropoiesis, or other unknown factors. Testosterone supplementation normalized
      the iron status and further stimulated splenic erythropoietic activity; both may
      contribute to improve the anemic condition in the old mice. 

PMID- 23974082
TI  - Co-precipitation synthesis and electrochemical properties of graphene supported
      LiMn1/3Ni1/3Co1/3O2 cathode materials for lithium-ion batteries.
AB  - Nanostructured graphene supported LiMn1/3Ni1/3Co1/3O2 has been prepared by the co
      precipitation method and used as the cathode material for lithium-ion batteries.
      The structure and morphology of the composite were examined using atomic force
      microscopy, scanning electron microscopy, high-resolution transmission electron
      microscopy, and x-ray diffraction. The composite cathodes made of graphene
      nanosheet supported LiMn1/3Ni1/3Co1/3O2 showed superior electrochemical
      performance and increased capacity compared to raw LiMn1/3Ni1/3Co1/3O2
      electrodes. The outstanding electrochemical behavior of graphene supported
      LiMn1/3Ni1/3Co1/3O2 was ascribed to the increased electrical conductivity and
      high structural stability resulting from the addition of graphene. 

PMID- 23974083
TI  - Primary care interventions to prevent tobacco use in children and adolescents:
      U.S. Preventive Services Task Force recommendation statement.
AB  - DESCRIPTION: Update of the 2003 U.S. Preventive Services Task Force (USPSTF)
      recommendation on primary care interventions to prevent tobacco use in children
      and adolescents. METHODS: The USPSTF reviewed the evidence on the effectiveness
      of primary care interventions on the rates of initiation or cessation of tobacco
      use in children and adolescents and on health outcomes, such as respiratory
      health, dental and oral health, and adult smoking. The USPSTF also reviewed the
      evidence on the potential harms of these interventions. POPULATION: This
      recommendation applies to school-aged children and adolescents. The USPSTF has
      issued a separate recommendation statement on tobacco use counseling in adults
      and pregnant women. RECOMMENDATION: The USPSTF recommends that primary care
      clinicians provide interventions, including education or brief counseling, to
      prevent initiation of tobacco use in school-aged children and adolescents.

PMID- 23974084
TI  - Maternal plasma bisulfite DNA sequencing: tomorrow starts today.

PMID- 23974085
TI  - Quantitative PCR measurement of tRNA 2-methylthio modification for assessing type
      2 diabetes risk.
AB  - BACKGROUND: Genetic variants in the human CDKAL1 (CDK5 regulatory subunit
      associated protein 1-like 1) gene have been associated with reduced insulin
      secretion and type 2 diabetes (T2D). CDKAL1 is a methylthiotransferase that
      catalyzes 2-methylthio (ms(2)) modification of the adenine at position 37 (A37)
      of cytoplasmic tRNA(Lys)(UUU). We investigated the ms(2)-modification level of
      tRNA(Lys)(UUU) as a direct readout of CDKAL1 enzyme activity in human samples.
      METHOD: We developed a quantitative PCR (qPCR)-based method to measure ms(2)
      modification. tRNA(Lys)(UUU) was reverse-transcribed with 2 unique primers:
      Reverse primer r1 was designed to anneal to the middle of this tRNA, including
      the nucleotide at A37, and reverse primer r2 was designed to anneal to the region
      downstream (3') of A37. Subsequent qPCR was performed to detect the corresponding
      transcribed cDNAs. RESULTS: The efficiency of reverse transcription of
      tRNA(Lys)(UUU) was ms(2)-modification dependent. The relative difference in
      threshold cycle number obtained with the r1 or r2 primer yielded the ms(2)
      modification level in tRNA(Lys)(UUU) precisely as predicted by an original
      mathematical model. The method was capable of measuring ms(2)-modification levels
      in tRNA(Lys)(UUU) in total RNA isolated from human peripheral blood samples,
      revealing that the ms(2)-modification rate in tRNA(Lys)(UUU) was decreased in
      individuals carrying the CDKAL1 genotype associated with T2D. In addition, the
      ms(2)-modification level was correlated with insulin secretion. CONCLUSIONS: The
      results point to the critical role of ms(2) modification in T2D and to a
      potential clinical use of a simple and high-throughput method for assessing T2D
      risk.

PMID- 23974086
TI  - Effect of CYP3A4*22, POR*28, and PPARA rs4253728 on sirolimus in vitro metabolism
      and trough concentrations in kidney transplant recipients.
AB  - BACKGROUND: Recent studies have identified new candidate polymorphisms in the
      genes related to CYP3A activity or calcineurin inhibitor dose requirements in
      kidney transplant recipients. These genes and polymorphisms are CYP3A4
      (cytochrome P450, family 3, subfamily A, polypeptide 4) (rs35599367-C>T; *22);
      POR [P450 (cytochrome) oxidoreductase] (rs1057868-C>T; *28); and PPARA
      (peroxisome proliferator-activated receptor alpha) (rs4253728-G>A). We
      investigated the impact of these polymorphisms on sirolimus (SRL) in vitro
      hepatic metabolism, SRL trough concentrations (C0), and SRL adverse events in
      kidney transplant recipients. METHODS: The clinical study included 113 stable
      kidney transplant patients switched from a calcineurin inhibitor to SRL (SRL C0
      measured at 1, 3, and 6 months thereafter). We investigated SRL metabolism in
      vitro using human liver microsomes derived from individual donors (n = 31).
      Microsomes and patients were genotyped by use of Taqman(r) allelic discrimination
      assays. The effects of polymorphisms and covariates were studied using
      multilinear regression imbedded in linear mixed-effect models or logistic
      regressions. RESULTS: In vitro, the CYP3A4*22 allele resulted in approximately
      20% lower metabolic rates of SRL (P = 0.0411). No significant association was
      found between CYP3A4, CYP3A5, or PPARA genotypes and SRL dose, C0, or C0/dose in
      kidney transplant patients. POR*28 was associated with a minor but significant
      decrease in SRL log-transformed C0 [CT/TT vs CC, beta = -0.15 (0.05); P = 0.0197]
      but this did not have any impact on the dose administered, which limited the
      relevance of the finding. After adjustment for nongenetic covariates and
      correction for false discovery finding, none of the single-nucleotide
      polymorphisms tested showed significant association with SRL adverse events.
      CONCLUSIONS: These recently described polymorphisms do not seem to substantially
      influence the pharmacokinetics of SRL or the occurrence of SRL adverse events in
      kidney transplant recipients.

PMID- 23974087
TI  - A new signaling paradigm to control the prenylation and trafficking of small
      GTPases.

PMID- 23974088
TI  - Myosin transcellular networks regulate epithelial apical geometry.

PMID- 23974089
TI  - The weakest link: a new paradigm for stabilizing the integrin-actin connection.

PMID- 23974090
TI  - EphA2 bears plasticity to tumor invasion.

PMID- 23974091
TI  - The compact view on heterochromatin.

PMID- 23974092
TI  - FACT and H3.3: new markers for the somatic hypermutation.

PMID- 23974093
TI  - When the Swiss clock goes wrong: regulation of Aurora A by UBXN-2/CDC-48.

PMID- 23974094
TI  - Interfering with type I interferon: a novel approach to purge persistent viral
      infection.

PMID- 23974095
TI  - Nuclear reprogramming of luminal-like breast cancer cells generates Sox2
      overexpressing cancer stem-like cellular states harboring transcriptional
      activation of the mTOR pathway.
AB  - Energy metabolism plasticity enables stemness programs during the reprogramming
      of somatic cells to an induced pluripotent stem cell (iPSC) state. This
      relationship may introduce a new era in the understanding of Warburg's theory on
      the metabolic origin of cancer at the level of cancer stem cells (CSCs). Here, we
      used Yamanaka's stem cell technology in an attempt to create stable CSC research
      lines in which to dissect the transcriptional control of mTOR--the master switch
      of cellular catabolism and anabolism--in CSC-like states. The rare colonies with
      iPSC-like morphology, obtained following the viral transduction of the Oct4,
      Sox2, Klf4, and c-Myc (OSKM) stemness factors into MCF-7 luminal-like breast
      cancer cells (MCF-7/Rep), demonstrated an intermediate state between cancer cells
      and bona fide iPSCs. MCF-7/Rep cells notably overexpressed SOX2 and stage
      specific embryonic antigen (SSEA)-4 proteins; however, other stemness-related
      markers (OCT4, NANOG, SSEA-1, TRA-1-60, and TRA-1-81) were found at low to
      moderate levels. The transcriptional analyses of OSKM factors confirmed the
      strong but unique reactivation of the endogenous Sox2 stemness gene accompanied
      by the silencing of the exogenous Sox2 transgene in MCF-7/Rep cells. Some but not
      all MCF-7/Rep cells acquired strong alkaline phosphatase (AP) activity compared
      with MCF-7 parental cells. SOX2-overexpressing MCF-7/Rep cells contained
      drastically higher percentages of CD44(+) and ALDEFLUOR-stained ALDH(bright)
      cells than MCF-7 parental cells. The overlap between differentially expressed
      mTOR signaling-related genes in 3 different SOX2-overexpressing CSC-like cell
      lines revealed a notable downregulation of 3 genes, PRKAA1 (which codes for the
      catalytic alpha 1 subunit of AMPK), DDIT4/REDD1 (a stress response gene that
      operates as a negative regulator of mTOR), and DEPTOR (a naturally occurring
      endogenous inhibitor of mTOR activity). The insulin-receptor gene (INSR) was
      differentially upregulated in MCF-7/Rep cells. Consistent with the downregulation
      of AMPK expression, immunoblotting procedures confirmed upregulation of p70S6K
      and increased phosphorylation of mTOR in Sox2-overexpressing CSC-like cell
      populations. Using an in vitro model of the de novo generation of CSC-like states
      through the nuclear reprogramming of an established breast cancer cell line, we
      reveal that the transcriptional suppression of mTOR repressors is an intrinsic
      process occurring during the acquisition of CSC-like properties by differentiated
      populations of luminal-like breast cancer cells. This approach may provide a new
      path for obtaining information about preventing the appearance of CSCs through
      the modulation of the AMPK/mTOR pathway.

PMID- 23974097
TI  - Tumor protein D52 represents a negative regulator of ATM protein levels.
AB  - Tumor protein D52 (TPD52) is a coiled-coil motif bearing hydrophilic polypeptide
      known to be overexpressed in cancers of diverse cellular origins. Increased TPD52
      expression is associated with increased proliferation and invasive capacity in
      different cell types. Recent studies have reported a correlation between TPD52
      transcript levels and G 2 chromosomal radiosensitivity in lymphocytes of women at
      risk of hereditary breast cancer, and that TPD52 knockdown significantly reduced
      the radiation sensitivity of multiple cancer cell lines. In this study, we
      investigated possible roles for TPD52 in DNA damage response, and found that
      increased TPD52 expression in breast cancer and TPD52-expressing BALB/c 3T3 cells
      compromised ATM-mediated cellular responses to DNA double-strand breaks induced
      by gamma-ray irradiation, which was associated with downregulation of steady
      state ATM protein, but not transcript levels, regardless of irradiation status.
      TPD52-expressing 3T3 cells also showed significantly increased radiation
      sensitivity compared with vector cells evaluated by clonogenic assays.
      Furthermore, direct interactions between exogenous and endogenous ATM and TPD52
      were detected by GST pull-down and co-immunoprecipitation assays. We also
      identified the interaction domains involved in this binding as TPD52 residues 111
      131, and ATM residues 1-245 and 772-1102. Taken together, our results suggest
      that TPD52 may represent a novel negative regulator of ATM protein levels. 

PMID- 23974096
TI  - Molecular dynamics of the full-length p53 monomer.
AB  - The p53 protein is frequently mutated in a very large proportion of human tumors,
      where it seems to acquire gain-of-function activity that facilitates tumor onset
      and progression. A possible mechanism is the ability of mutant p53 proteins to
      physically interact with other proteins, including members of the same family,
      namely p63 and p73, inactivating their function. Assuming that this interaction
      might occurs at the level of the monomer, to investigate the molecular basis for
      this interaction, here, we sample the structural flexibility of the wild-type p53
      monomeric protein. The results show a strong stability up to 850 ns in the DNA
      binding domain, with major flexibility in the N-terminal transactivations domains
      (TAD1 and TAD2) as well as in the C-terminal region (tetramerization domain).
      Several stable hydrogen bonds have been detected between N-terminal or C-terminal
      and DNA binding domain, and also between N-terminal and C-terminal. Essential
      dynamics analysis highlights strongly correlated movements involving TAD1 and the
      proline-rich region in the N-terminal domain, the tetramerization region in the C
      terminal domain; Lys120 in the DNA binding region. The herein presented model is
      a starting point for further investigation of the whole protein tetramer as well
      as of its mutants. 

PMID- 23974098
TI  - Seeing is believing: the MCM2-7 helicase trapped in complex with its DNA loader.

PMID- 23974099
TI  - CDK4/6-inhibiting drug substitutes for p21 and p16 in senescence: duration of
      cell cycle arrest and MTOR activity determine geroconversion.
AB  - CDKN1A (p21) and CDKN2A (p16) inhibit CDK4/6, initiating senescence. According to
      our view on senescence, the role of p21 and p16 is to cause cell cycle arrest,
      whereas MTOR (mechanistic target of rapamycin) drives geroconversion to
      senescence. Recently we demonstrated that one of the markers of p21- and p16
      initiated senescence is MEK-dependent hyper-elevation of cyclin D1. We noticed
      that a synthetic inhibitor of CDK 4/6 (PD0332991) also induced cyclin D1-positive
      senescence. We demonstrated that PD0332991 and p21 caused almost identical
      senescence phenotypes. p21, p16, and PD0332991 do not inhibit MTOR, and rapamycin
      decelerates geroconversion caused by all 3 molecules. Like p21, PD0332991
      initiated senescence at any concentration that inhibited cell proliferation. This
      confirms the notion that a mere arrest in the presence of active MTOR may lead to
      senescence. 

PMID- 23974100
TI  - NFkappaB regulates expression of Polo-like kinase 4.
AB  - Activation of the NFkappaB signaling pathway allows the cell to respond to
      infection and stress and can affect many cellular processes. As a consequence,
      NFkappaB activity must be integrated with a wide variety of parallel signaling
      pathways. One mechanism through which NFkappaB can exert widespread effects is
      through controlling the expression of key regulatory kinases. Here we report that
      NFkappaB regulates the expression of genes required for centrosome duplication,
      and that Polo-like kinase 4 (PLK4) is a direct NFkappaB target gene. RNA
      interference, chromatin immunoprecipitation, and analysis of the PLK4 promoter in
      a luciferase reporter assay revealed that all NFkappaB subunits participate in
      its regulation. Moreover, we demonstrate that NFkappaB regulation of PLK4
      expression is seen in multiple cell types. Significantly long-term deletion of
      the NFkappaB2 (p100/p52) subunit leads to defects in centrosome structure. This
      data reveals a new component of cell cycle regulation by NFkappaB and suggests a
      mechanism through which deregulated NFkappaB activity in cancer can lead to
      increased genomic instability and uncontrolled proliferation. 

PMID- 23974101
TI  - E2F-7 couples DNA damage-dependent transcription with the DNA repair process.
AB  - The cellular response to DNA damage, mediated by the DNA repair process, is
      essential in maintaining the integrity and stability of the genome. E2F-7 is an
      atypical member of the E2F family with a role in negatively regulating
      transcription and cell cycle progression under DNA damage. Surprisingly, we found
      that E2F-7 makes a transcription-independent contribution to the DNA repair
      process, which involves E2F-7 locating to and binding damaged DNA. Further, E2F-7
      recruits CtBP and HDAC to the damaged DNA, altering the local chromatin
      environment of the DNA lesion. Importantly, the E2F-7 gene is a target for
      somatic mutation in human cancer and tumor-derived mutant alleles encode proteins
      with compromised transcription and DNA repair properties. Our results establish
      that E2F-7 participates in 2 closely linked processes, allowing it to directly
      couple the expression of genes involved in the DNA damage response with the DNA
      repair machinery, which has relevance in human malignancy. 

PMID- 23974103
TI  - Endogenously produced hydrogen sulfide supports tumor cell growth and
      proliferation.

PMID- 23974102
TI  - Metabolic profiling of human CD4+ cells following treatment with methotrexate and
      anti-TNF-alpha infliximab.
AB  - The autoimmune process in rheumatoid arthritis depends on activation of immune
      cells, which utilize intracellular kinases to respond to external stimuli such as
      cytokines, immune complexes, and antigens. CD4+ T cells comprise a large
      proportion of the inflammatory cells that invade the synovial tissue and may
      therefore be a cell type of pathogenic importance. Both methotrexate and
      infliximab are effective in the treatment of inflammatory arthritis; however, the
      biological effects triggered by these treatments and the biochemical mechanisms
      underlining the cell response are still not fully understood. Thus, in this study
      the global metabolic changes associated with methotrexate or infliximab treatment
      of isolated human CD4+ T cells were examined using gas chromatography/mass
      spectrometry or liquid chromatography/mass spectrometry. In total 148 metabolites
      involved in selective pathways were found to be significantly altered. Overall,
      the changes observed are likely to reflect the effort of CD4+ cells to increase
      the production of cellular reducing power to offset the cellular stress exerted
      by treatment. Importantly, analysis of the global metabolic changes associated
      with MTX or infliximab treatment of isolated human CD4+ T cells suggested that
      the toxicity associated with these agents is minimal when used at clinically
      relevant concentrations. 

PMID- 23974104
TI  - High-throughput screen identifies disulfiram as a potential therapeutic for
      triple-negative breast cancer cells: interaction with IQ motif-containing
      factors.
AB  - Triple-negative breast cancer (TNBC) represents an aggressive subtype, for which
      radiation and chemotherapy are the only options. Here we describe the
      identification of disulfiram, an FDA-approved drug used to treat alcoholism, as
      well as the related compound thiram, as the most potent growth inhibitors
      following high-throughput screens of 3185 compounds against multiple TNBC cell
      lines. The average IC50 for disulfiram was ~300 nM. Drug affinity responsive
      target stability (DARTS) analysis identified IQ motif-containing factors IQGAP1
      and MYH9 as direct binding targets of disulfiram. Indeed, knockdown of these
      factors reduced, though did not completely abolish, cell growth. Combination
      treatment with 4 different drugs commonly used to treat TNBC revealed that
      disulfiram synergizes most effectively with doxorubicin to inhibit cell growth of
      TNBC cells. Disulfiram and doxorubicin cooperated to induce cell death as well as
      cellular senescence, and targeted the ESA(+)/CD24(-/low)/CD44(+) cancer stem cell
      population. Our results suggest that disulfiram may be repurposed to treat TNBC
      in combination with doxorubicin.

PMID- 23974105
TI  - TGF-beta: an emerging player in drug resistance.
AB  - The transforming growth factor beta (TGF-beta) pathway acts as a double-edged
      sword in tumorigenesis. By constraining epithelial cell growth, TGF-beta is a
      potent tumor suppressor. However, TGF-beta also acts as a key player in the
      induction of epithelial-to-mesenchymal transition (EMT), thereby enhancing
      invasiveness and metastasis. Furthermore, TGF-beta signaling has recently been
      correlated with resistance against both targeted and conventional anticancer
      agents. Here, we present data demonstrating a role for TGF-beta in chemotherapy
      resistance in colorectal cancer (CRC). We discuss these results in the context of
      recent findings indicating TGF-beta signaling as an emerging player in cancer
      drug resistance. 

PMID- 23974106
TI  - Remodeling and spacing factor 1 (RSF1) deposits centromere proteins at DNA double
      strand breaks to promote non-homologous end-joining.
AB  - The cellular response to ionizing radiation (IR)-induced DNA double-strand breaks
      (DSBs) in native chromatin requires a tight coordination between the activities
      of DNA repair machineries and factors that modulate chromatin structure. SMARCA5
      is an ATPase of the SNF2 family of chromatin remodeling factors that has recently
      been implicated in the DSB response. It forms distinct chromatin remodeling
      complexes with several non-canonical subunits, including the remodeling and
      spacing factor 1 (RSF1) protein. Despite the fact that RSF1 is often
      overexpressed in tumors and linked to tumorigenesis and genome instability, its
      role in the DSB response remains largely unclear. Here we show that RSF1
      accumulates at DSB sites and protects human cells against IR-induced DSBs by
      promoting repair of these lesions through homologous recombination (HR) and non
      homologous end-joining (NHEJ). Although SMARCA5 regulates the RNF168-dependent
      ubiquitin response that targets BRCA1 to DSBs, we found RSF1 to be dispensable
      for this process. Conversely, we found that RSF1 facilitates the assembly of
      centromere proteins CENP-S and CENP-X at sites of DNA damage, while SMARCA5 was
      not required for these events. Mechanistically, we uncovered that CENP-S and CENP
      X, upon their incorporation by RSF1, promote assembly of the NHEJ factor XRCC4 at
      damaged chromatin. In contrast, CENP-S and CENP-X were dispensable for HR,
      suggesting that RSF1 regulates HR independently of these centromere proteins. Our
      findings reveal distinct functions of RSF1 in the 2 major pathways of DSB repair
      and explain how RSF1, through the loading of centromere proteins and XRCC4 at
      DSBs, promotes repair by non-homologous end-joining. 

PMID- 23974107
TI  - Cell context in the control of self-renewal and proliferation regulated by MLL1.
AB  - Mixed lineage leukemia 1 (MLL1) is a gene that is disrupted by chromosomal
      translocation characteristically in a large proportion of infant leukemia and
      also in a fraction of childhood and adult leukemia. MLL1 encodes a chromatin
      regulatory protein related to the Drosophila Trithorax protein, a well-studied
      epigenetic factor that functions during development to maintain expression of its
      target genes. Although tremendous progress has been made understanding the
      downstream targets of MLL1 fusion oncoproteins and how manipulation of those
      targets impacts leukemogenesis, very little is known regarding how the initial
      expression of an MLL1 fusion protein impacts on that cell's behavior,
      particularly how the cell cycle is affected. Here, we focused on the function of
      endogenous MLL1 in the stem and progenitor cell types that are likely to be
      transformed upon MLL1 translocation. Our studies reveal a differential response
      of stem or progenitor populations to acute loss of MLL1 on proliferation and
      survival. These data suggest that the effects of MLL1 fusion oncoproteins will
      initiate the leukemogenic process differentially depending on the differentiation
      state of the cell type in which the translocation occurs. 

PMID- 23974108
TI  - Rac1 drives intestinal stem cell proliferation and regeneration.
AB  - Adult stem cells are responsible for maintaining the balance between cell
      proliferation and differentiation within self-renewing tissues. The molecular and
      cellular mechanisms mediating such balance are poorly understood. The production
      of reactive oxygen species (ROS) has emerged as an important mediator of stem
      cell homeostasis in various systems. Our recent work demonstrates that Rac1
      dependent ROS production mediates intestinal stem cell (ISC) proliferation in
      mouse models of colorectal cancer (CRC). Here, we use the adult Drosophila midgut
      and the mouse small intestine to directly address the role of Rac1 in ISC
      proliferation and tissue regeneration in response to damage. Our results
      demonstrate that Rac1 is necessary and sufficient to drive ISC proliferation and
      regeneration in an ROS-dependent manner. Our data point to an evolutionarily
      conserved role of Rac1 in intestinal homeostasis and highlight the value of
      combining work in the mammalian and Drosophila intestine as paradigms to study
      stem cell biology. 

PMID- 23974109
TI  - Unbiased transcriptome signature of in vivo cell proliferation reveals pro- and
      antiproliferative gene networks.
AB  - Different types of mature B-cell lymphocytes are overall highly similar.
      Nevertheless, some B cells proliferate intensively, while others rarely do. Here,
      we demonstrate that a simple binary classification of gene expression in
      proliferating vs. resting B cells can identify, with remarkable selectivity,
      global in vivo regulators of the mammalian cell cycle, many of which are also
      post-translationally regulated by the APC/C E3 ligase. Consequently, we discover
      a novel regulatory network between the APC/C and the E2F transcription factors
      and discuss its potential impact on the G1-S transition of the cell cycle. In
      addition, by focusing on genes whose expression inversely correlates with
      proliferation, we demonstrate the inherent ability of our approach to also
      identify in vivo regulators of cell differentiation, cell survival, and other
      antiproliferative processes. Relying on data sets of wt, non-transgenic animals,
      our approach can be applied to other cell lineages and human data sets.

PMID- 23974110
TI  - Gravitational force modulates G2/M phase exit in mechanically unloaded myoblasts.
AB  - Prolonged spaceflight gives rise to muscle loss and reduced strength, a condition
      commonly referred to as space atrophy. During exposure to microgravity, skeletal
      muscle myoblasts are mechanically unloaded and respond with attenuated cell
      proliferation, slowed cell cycle progression, and modified protein expression. To
      elucidate the underlying mechanisms by which muscle mass declines in response to
      prolonged microgravity exposure, we grew C2C12 mouse muscle cells under
      conditions of simulated microgravity (SM) and analyzed their proliferative
      capacity, cell cycle progression, and cyclin B and D expression. We demonstrated
      that the retarded cell growth observed in SM was correlated with an approximate
      16 h delay in G2/M phase progression, where cells accumulated specifically
      between the G2 checkpoint and the onset of anaphase, concomitantly with a
      positive expression for cyclin B. The effect was specific for gravitational
      mechanical unloading as cells grown under conditions of hypergravity (HG, 4 g)
      for similar durations of time exhibited normal proliferation and normal cell
      cycle progression. Our results show that SM and HG exert phenomenological
      distinct responses over cell cycle progression. The deficits of SM can be
      restored by terrestrial gravitational force, whereas the effects of HG are
      indistinguishable from the 1 g control. This suggests that the
      mechanotransduction apparatus of cells responds differently to mechanical
      unloading and loading.

PMID- 23974111
TI  - EGFR inhibitors exacerbate differentiation and cell cycle arrest induced by
      retinoic acid and vitamin D3 in acute myeloid leukemia cells.
AB  - By means of an unbiased, automated fluorescence microscopy-based screen, we
      identified the epidermal growth factor receptor (EGFR) inhibitors erlotinib and
      gefitinib as potent enhancers of the differentiation of HL-60 acute myeloid
      leukemia (AML) cells exposed to suboptimal concentrations of vitamin A (all-trans
      retinoic acid, ATRA) or vitamin D (1alpha,25-hydroxycholecalciferol, VD).
      Erlotinib and gefitinib alone did not promote differentiation, yet stimulated the
      acquisition of morphological and biochemical maturation markers (including the
      expression of CD11b and CD14 as well as increased NADPH oxidase activity) when
      combined with either ATRA or VD. Moreover, the combination of erlotinib and ATRA
      or VD synergistically induced all the processes that are normally linked to
      terminal hematopoietic differentiation, namely, a delayed proliferation arrest in
      the G0/G1 phase of the cell cycle, cellular senescence, and apoptosis. Erlotinib
      potently inhibited the (auto)phosphorylation of mitogen-activated protein kinase
      14 (MAPK14, best known as p38(MAPK)) and SRC family kinases (SFKs). If combined
      with the administration of ATRA or VD, the inhibition of p38(MAPK) or SFKs with
      specific pharmacological agents mimicked the pro-differentiation activity of
      erlotinib. These data were obtained with 2 distinct AML cell lines (HL-60 and
      MOLM-13 cells) and could be confirmed on primary leukemic blasts isolated from
      the circulation of AML patients. Altogether, these findings point to a new
      regimen for the treatment of AML, in which naturally occurring pro
      differentiation agents (ATRA or VD) may be combined with EGFR inhibitors.

PMID- 23974112
TI  - SEACing the GAP that nEGOCiates TORC1 activation: evolutionary conservation of
      Rag GTPase regulation.
AB  - The target of rapamycin complex 1 (TORC1) regulates eukaryotic cell growth in
      response to a variety of input signals. In S. cerevisiae, amino acids activate
      TORC1 through the Rag guanosine triphosphatase (GTPase) heterodimer composed of
      Gtr1 and Gtr2 found together with Ego1 and Ego3 in the EGO complex (EGOC). The
      GTPase activity of Gtr1 is regulated by the SEA complex (SEAC). Specifically,
      SEACIT, a SEAC subcomplex containing Iml1, Npr2, and Npr3 functions as a GTPase
      activator (GAP) for Gtr1 to decrease the activity of TORC1 and, consequently,
      growth, after amino acid deprivation. Here, we present genetic epistasis data,
      which show that SEACAT, the other SEAC subcomplex, containing Seh1, Sea2-4, and
      Sec13, antagonizes the GAP function of SEACIT. Orthologs of EGOC (Ragulator),
      SEACIT (GATOR1), and SEACAT (GATOR2) are present in higher eukaryotes,
      highlighting the remarkable conservation, from yeast to man, of Rag GTPase and
      TORC1 regulation. 

PMID- 23974113
TI  - BAF chromatin remodeling complex: cortical size regulation and beyond.
AB  - The multi-subunit chromatin remodeling BAF complex controls different
      developmental processes. Using cortex-specific conditional knockout and
      overexpression mouse models, we have recently reported that BAF170, a subunit of
      the vertebrate BAF chromatin remodeling complex, interacts with transcription
      factor (TF) Pax6 to control cortical size and volume. The mechanistic basis
      includes suppression of the expression of Pax6 target genes, which are required
      for genesis of cortical intermediate progenitors (IPs) and specification of late
      neuronal subtype identity. In addition, we showed that a dynamic competition
      between BAF170 and BAF155 subunits within the BAF complex during progression of
      neurogenesis is a primary event in modulating the size of the mammalian cortex.
      Here, we present additional insights into the interaction between the BAF complex
      and TF Pax6 in the genesis of IPs of the developing cortex. Furthermore, we show
      that such competition between BAF170 and BAF155 is involved as well in the
      determination of the size of the embryonic body. Our results add new insights
      into a cell-intrinsic mechanism, mediated by the chromatin remodeling BAF complex
      that controls vertebrate body shape and size. 

PMID- 23974114
TI  - Protect and serve: Bcl-2 proteins as guardians and rulers of cancer cell
      survival.
AB  - It is widely accepted that anti-apoptotic Bcl-2 family members promote cancer
      cell survival by binding to their pro-apoptotic counterparts, thereby preventing
      mitochondrial outer membrane permeabilization (MOMP) and cytotoxic caspase
      activation. Yet, these proteins do not only function as guardians of
      mitochondrial permeability, preserving it, and maintaining cell survival in the
      face of acute or chronic stress, they also regulate non-apoptotic functions of
      caspases and biological processes beyond MOMP from diverse subcellular
      localizations and in complex with numerous binding partners outside of the Bcl-2
      family. In particular, some of the non-canonical effects and functions of Bcl-2
      homologs lead to an interplay with E2F-1, NFkappaB, and Myc transcriptional
      pathways, which themselves influence cancer cell growth and survival. We thus
      propose that, by feedback loops that we currently have only hints of, Bcl-2
      proteins may act as rulers of survival signaling, predetermining the apoptotic
      threshold that they also directly scaffold. This underscores the robustness of
      the control exerted by Bcl-2 homologs over cancer cell survival, and implies that
      small molecules compounds currently used in the clinic to inhibit their
      mitochondrial activity may be not always be fully efficient to override this
      control. 

PMID- 23974115
TI  - Intermolecular domain swapping induces intein-mediated protein alternative
      splicing.
AB  - Protein sequences are diversified on the DNA level by recombination and mutation
      and can be further increased on the RNA level by alternative RNA splicing,
      involving introns that have important roles in many biological processes. The
      protein version of introns (inteins), which catalyze protein splicing, were first
      reported in the 1990s. The biological roles of protein splicing still remain
      elusive because inteins neither provide any clear benefits nor have an essential
      role in their host organisms. We now report protein alternative splicing, in
      which new protein sequences can be produced by protein recombination by
      intermolecular domain swapping of inteins, as elucidated by NMR spectroscopy and
      crystal structures. We demonstrate that intein-mediated protein alternative
      splicing could be a new strategy to increase protein diversity (that is,
      functions) without any modification in genetic backgrounds. We also exploited it
      as a post-translational protein conformation-driven switch of protein functions
      (for example, as highly specific protein interference). 

PMID- 23974116
TI  - Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer.
AB  - Enhancer of zeste homolog 2 (EZH2) is the histone lysine N-methyltransferase
      component of the Polycomb repressive complex 2 (PRC2), which, in conjunction with
      embryonic ectoderm development (EED) and suppressor of zeste 12 homolog,
      regulates cell lineage determination and homeostasis. Enzymatic hyperactivity has
      been linked to aberrant repression of tumor suppressor genes in diverse cancers.
      Here, we report the development of stabilized alpha-helix of EZH2 (SAH-EZH2)
      peptides that selectively inhibit H3 Lys27 trimethylation by dose-responsively
      disrupting the EZH2-EED complex and reducing EZH2 protein levels, a mechanism
      distinct from that reported for small-molecule EZH2 inhibitors targeting the
      enzyme catalytic domain. MLL-AF9 leukemia cells, which are dependent on PRC2,
      undergo growth arrest and monocyte-macrophage differentiation upon treatment with
      SAH-EZH2, consistent with observed changes in expression of PRC2-regulated,
      lineage-specific marker genes. Thus, by dissociating the EZH2-EED complex, we
      pharmacologically modulate an epigenetic 'writer' and suppress PRC2-dependent
      cancer cell growth. 

PMID- 23974117
TI  - Small-molecule antagonists of melanopsin-mediated phototransduction.
AB  - Melanopsin, expressed in a subset of retinal ganglion cells, mediates behavioral
      adaptation to ambient light and other non-image-forming photic responses. This
      has raised the possibility that pharmacological manipulation of melanopsin can
      modulate several central nervous system responses, including photophobia, sleep,
      circadian rhythms and neuroendocrine function. Here we describe the
      identification of a potent synthetic melanopsin antagonist with in vivo activity.
      New sulfonamide compounds inhibiting melanopsin (opsinamides) compete with
      retinal binding to melanopsin and inhibit its function without affecting rod- and
      cone-mediated responses. In vivo administration of opsinamides to mice
      specifically and reversibly modified melanopsin-dependent light responses,
      including the pupillary light reflex and light aversion. The discovery of
      opsinamides raises the prospect of therapeutic control of the melanopsin
      phototransduction system to regulate light-dependent behavior and remediate
      pathological conditions. 

PMID- 23974118
TI  - Co-existence of distinct prion types enables conformational evolution of human
      PrPSc by competitive selection.
AB  - The unique phenotypic characteristics of mammalian prions are thought to be
      encoded in the conformation of pathogenic prion proteins (PrP(Sc)). The molecular
      mechanism responsible for the adaptation, mutation, and evolution of prions
      observed in cloned cells and upon crossing the species barrier remains unsolved.
      Using biophysical techniques and conformation-dependent immunoassays in tandem,
      we isolated two distinct populations of PrP(Sc) particles with different
      conformational stabilities and aggregate sizes, which frequently co-exist in the
      most common human prion disease, sporadic Creutzfeldt-Jakob disease. The protein
      misfolding cyclic amplification replicates each of the PrP(Sc) particle types
      independently and leads to the competitive selection of those with lower initial
      conformational stability. In serial propagation with a nonglycosylated mutant
      PrP(C) substrate, the dominant PrP(Sc) conformers are subject to further
      evolution by natural selection of the subpopulation with the highest replication
      rate due to its lowest stability. Cumulatively, the data show that sporadic
      Creutzfeldt-Jakob disease PrP(Sc) is not a single conformational entity but a
      dynamic collection of two distinct populations of particles. This implies the co
      existence of different prions, whose adaptation and evolution are governed by the
      selection of progressively less stable, faster replicating PrP(Sc) conformers. 

PMID- 23974120
TI  - Stability of phenytoin sodium suspensions for the treatment of open wounds.
AB  - The objective of this study was to evaluate the stability of two phenytoin sodium
      suspensions in 0.9% sodium chloride solution for use in noninstitutional settings
      (where pharmacies are not present) to dispense phenytoin on a daily basis. A
      generic extended phenytoin sodium (Mylan) and a name brand phenytoin sodium
      (Dilantin) in suspension form were evaluated. Both suspensions were first
      assessed for degradation during frozen storage at designated time intervals.
      Frozen samples were compared with freshly prepared samples. The chemical
      stability of phenytoin concentration in the samples was assessed by using a high
      performance liquid chromatography analytical technique. During the course of the
      experiment, the samples showed no crystallization and the pH remained in a range
      of 10.6 to 10.73. The suspensions were tested for contamination. The results show
      that Dilantin and Mylan suspensions remained stable and free of contamination.
      Suspensions of phenytoin sodium in 0.9% sodium chloride solution are stable at
      room temperature for at least 2 weeks. 

PMID- 23974119
TI  - FoxO3 transcription factor and Sirt6 deacetylase regulate low density lipoprotein
      (LDL)-cholesterol homeostasis via control of the proprotein convertase
      subtilisin/kexin type 9 (Pcsk9) gene expression.
AB  - Elevated LDL-cholesterol is a risk factor for the development of cardiovascular
      disease. Thus, proper control of LDL-cholesterol homeostasis is critical for
      organismal health. Genetic analysis has identified PCSK9 (proprotein convertase
      subtilisin/kexin type 9) as a crucial gene in the regulation of LDL-cholesterol
      via control of LDL receptor degradation. Although biochemical characteristics and
      clinical implications of PCSK9 have been extensively investigated, epigenetic
      regulation of this gene is largely unknown. In this work we have discovered that
      Sirt6, an NAD(+)-dependent histone deacetylase, plays a critical role in the
      regulation of the Pcsk9 gene expression in mice. Hepatic Sirt6 deficiency leads
      to elevated Pcsk9 gene expression and LDL-cholesterol as well. Mechanistically,
      we have demonstrated that Sirt6 can be recruited by forkhead transcription factor
      FoxO3 to the proximal promoter region of the Pcsk9 gene and deacetylates histone
      H3 at lysines 9 and 56, thereby suppressing the gene expression. Also remarkably,
      overexpression of Sirt6 in high fat diet-fed mice lowers LDL-cholesterol.
      Overall, our data suggest that FoxO3 and Sirt6, two longevity genes, can reduce
      LDL-cholesterol levels through regulation of the Pcsk9 gene. 

PMID- 23974121
TI  - Levorphanol, Methadone, and the Management of Intractable Chronic Pain: An
      Interview with Kerry Schmidt, BA,MBA; Jack P. McNulty, MD,FACP; and George B.
      Muller, RPh.
AB  - For former National Football League player Kerry Schmidt, BA,MBA, chronic pain is
      a part of everyday life. To repair sports-related trauma sustained during his 6
      year career as a defensive back, Schmidt has undergone 24 major orthopedic
      surgeries over the past three decades and will undergo two or three additional
      procedures to repair his lower back. Now a sports reporter, a syndicated sports
      columnist, and a business owner, Schmidt says his pain at times has rated a 10
      plus on a 10-point pain scale. Schmidt recently took control of his constant
      discomfort. After he consulted with Jack P. McNulty, MD,FACP, a specialist in the
      management of chronic pain, who collaborated with George B. Muller, RPh, a
      compounding pharmacist, Schmidt found relief with no adverse effects from the
      seldom-prescribed drug levorphanol. 

PMID- 23974122
TI  - Transdermal Administration of Anti-inflammatory Medications in Sports Injuries:
      Use of Iontophoresis and Phonophoresis to Enhance Delivery.
AB  - Transdermal delivery of anti-inflammatory medications, both nonsteroidal and
      corticosteroids, has enjoyed at least a decade of success in Canada and the US.
      Iontophoresis and phonophoresis offer substantial benefits for the transdermal
      delivery of these medications and can be valuable additions to existing treatment
      modalities for minor sports-related injuries. Included with this article is
      historical and explanatory information about iontophoresis and phonophoresis, as
      well as formulations and case reports related to the treatment of sports-related
      injuries. The article emphasizes the importance of a compounding pharmacist's
      involvement in developing a successful treatment plan. 

PMID- 23974123
TI  - Pharmaceutical legislation: an historical perspective.
AB  - Pharmaceutical quality and consistency has been a focus of pharmaceutical
      legislation in the United States for well over a century. The first such
      legislative initiative was the Drug Importation Act of 1848. It was the 1906 Pure
      Food and Drug Act, however, that first brought the issues of drug safety to the
      attention of the public. This law was the first to designate the United States
      Pharmacopeia and National Formulary as standards for quality of drugs prepared in
      the US. Subsequent legislation and amendments addressed loopholes in this law,
      but it wasn't until the Food, Drug and Cosmetic Act was passed in 1938 that
      fraudulent and misleading claims for pharaceutical products were addressed. This
      essay describes each pharmaceutical legislative initiative in the context of
      pharmacy practice of the time. 

PMID- 23974124
TI  - Pharmacy compounding urban legends.
AB  - This article reviews and clarifies a small sampling of the myths, or urban
      legends, about compounding. Included are comments on United sTates Pharmacopeia
      Chapter 797, environmental issues related to sterile compounding, and suggested
      resources for clarification of some of these myths. This article recommends a
      knowledge-based partnership between compounding pharmacists and pharmaceutical
      manufacturers to improve compounding activities and quality assurance methods to
      ensure that compounded medications are safe.

PMID- 23974125
TI  - Basics of compounding: application of the United States pharmacopeia bacterial
      endotoxins test to compounded sterile preparations.
AB  - This article introduces endotoxins and the application of the bacterial
      endotoxins (pyrogen) test to test for endotoxins in a manner compliant with the
      United States Pharmacopeia-National Formulary Chapter 797 Pharmaceutical
      Compounding-Sterile Preparations, the intent of which is to prevent harm and
      fatality to patients which could result from microbial contamination
      (nonsterility), excessive bacterial endotoxins, or compounding errors. Basic
      information about endotoxins is supplied in this article, along with information
      on testing methods. The purpose of this article is to assist compounding
      pharmacists to develop a documented system in which the quality of the components
      and the compounding procedure are well controlled and testing for endotoxins
      becomes a formality. 

PMID- 23974126
TI  - Quality-Control Analytical Methods: Common Concerns about Out-of-Specification
      Results.
AB  - When results of potency testing of a compounded preparation do not meet the
      desired specifications, concerns abound and questions are presented. The purpose
      of this article is to address some of the most common questions and to provide
      potential solutions. It addresses the investigative process used to determine the
      cause of unexpected potency test results, defines the term "out-of
      specification," discusses the organization responsible for defining the
      acceptable specifications, explains the differences between a laboratory out-of
      specification and a compounded preparation out-of-specification, describes the
      retesting procedure, outlines some of the possible reasons and remedies for out
      of-specification results, and suggests practices to minimize error in compounding
      preparations. Compounding pharmacists should consider making the references and
      resource provided in this article readily available at their compounding
      facility. 

PMID- 23974127
TI  - Acacia and mineral oil emulsion NF.

PMID- 23974128
TI  - "How'd They do That?".
AB  - For the purpose of this article "success" is defined as compounding more
      prescriptions on a daily basis. Based on that defintion, an online survey for
      compounding pharmacists was developed and conducted. This article provides an
      overview of the results of that survey. The purpose of this survey was not to
      imply that attaining a goal of high volume determined success but to compare and
      contrast pharmacies that reported high volumes of compounding with those that
      reported lower volumes of compounding. Subjects of some of the major services
      provided by compounding pharmacists are discussed in this article, including:
      sterile and nonsterile compounding, consultations, over-the-counter services,
      pharmacy websites, and marketing. 

PMID- 23974129
TI  - Stability of morphine sulfate in polypropylene infusion bags for use in patient
      controlled analgesia pumps for postoperative pain management.
AB  - The objective of this study was to develop a stable intravenous solution of 1
      mg/mL morphine sulfate in polypropylene bags for use in patient-controlled
      analgesia pumps for postoperative pain management. Three large-scale batches of 1
      mg/mL morphine sulfate solution filled into polypropylene bags and terminally
      sterilized at 120 deg C for 20 minutes were used in this study. The stability of
      the drug was monitored at 3, 6, 12, 18, 24, and 36 months after preparation in a
      long-term study (25 deg C) and after 3 and 6 months in accelerated studies (30
      and 40 deg C) using a stability-indicating high-performance liquid chromatography
      assay. The levels of degradation products (morphine-N-oxide and pseudomorphine)
      were determined. Measures of physical stability included pH values, presence of
      subvisible particles, and weight loss. Microbiological stability was tested by
      performing sterility test. There was practically no loss of morphine, and
      impurity contents were very low. Subvisible particles were below pharmacopeial
      specifications. No significant change in pH was observed and water losses were
      minimal. The sterility of the bags was demonstrated throughout the study. In
      conclusion, terminally sterilized 1-mg/mL morphine sulfate solution packed in
      polypropylene bags is stable for at least 3 years when stored at 25 deg C. 

PMID- 23974130
TI  - Do mesenchymal stem cells modulate the milieu of reconstructed bladder wall?
AB  - To evaluate the mesenchymal stem cells (MSCs) influence on cytokines and matrix
      metalloproteinases (MMPs) expression in rat bladder wall regeneration. MSCs
      cultures from the bone marrow were established. Acellular matrices from the
      bladder submucosa were prepared. Bladders were reconstructed using cell-seeded (n
      = 5) and unseeded (n = 5) grafts. MSCs were injected into the bladder wall (n =
      5), bladders were incised and MSCs were injected into the circulation (n = 5) or
      were left intact (n = 5). Animals were killed after 3 months. Bladder histology
      and immunohistochemical staining of IL-2, IL-4, IL-6, IL-10, TNF-alpha, TGF
      beta1, IFN-gamma, MMP-2, and MMP-9 were done. Bladders reconstructed with cell
      seeded grafts mimicked native tissue, while unseeded grafts revealed shrinkage
      and morphological irregularities. There were no morphological changes in bladders
      of other groups. Different pattern of cytokine and MMP expression was observed.
      Increased expression of anti-inflammatory cytokines and MMPs in bladder promotes
      detrusor regeneration. 

PMID- 23974131
TI  - Differential gene expression in Pycnoporus coccineus during interspecific
      mycelial interactions with different competitors.
AB  - Fungi compete against each other for environmental resources. These interspecific
      combative interactions encompass a wide range of mechanisms. In this study, we
      highlight the ability of the white-rot fungus Pycnoporus coccineus to quickly
      overgrow or replace a wide range of competitor fungi, including the gray-mold
      fungus Botrytis cinerea and the brown-rot fungus Coniophora puteana. To gain a
      better understanding of the mechanisms deployed by P. coccineus to compete
      against other fungi and to assess whether common pathways are used to interact
      with different competitors, differential gene expression in P. coccineus during
      cocultivation was assessed by transcriptome sequencing and confirmed by
      quantitative reverse transcription-PCR analysis of a set of 15 representative
      genes. Compared with the pure culture, 1,343 transcripts were differentially
      expressed in the interaction with C. puteana and 4,253 were differentially
      expressed in the interaction with B. cinerea, but only 197 transcripts were
      overexpressed in both interactions. Overall, the results suggest that a broad
      array of functions is necessary for P. coccineus to replace its competitors and
      that different responses are elicited by the two competitors, although a portion
      of the mechanism is common to both. However, the functions elicited by the
      expression of specific transcripts appear to converge toward a limited set of
      roles, including detoxification of secondary metabolites. 

PMID- 23974132
TI  - Lysobacter enzymogenes uses two distinct cell-cell signaling systems for
      differential regulation of secondary-metabolite biosynthesis and colony
      morphology.
AB  - Lysobacter enzymogenes is a ubiquitous environmental bacterium that is emerging
      as a potentially novel biological control agent and a new source of bioactive
      secondary metabolites, such as the heat-stable antifungal factor (HSAF) and
      photoprotective polyene pigments. Thus far, the regulatory mechanism(s) for
      biosynthesis of these bioactive secondary metabolites remains largely unknown in
      L. enzymogenes. In the present study, the diffusible signal factor (DSF) and
      diffusible factor (DF)-mediated cell-cell signaling systems were identified for
      the first time from L. enzymogenes. The results show that both Rpf/DSF and DF
      signaling systems played critical roles in modulating HSAF biosynthesis in L.
      enzymogenes. Rpf/DSF signaling and DF signaling played negative and positive
      effects in polyene pigment production, respectively, with DF playing a more
      important role in regulating this phenotype. Interestingly, only Rpf/DSF, but not
      the DF signaling system, regulated colony morphology of L. enzymgenes. Both
      Rpf/DSF and DF signaling systems were involved in the modulation of expression of
      genes with diverse functions in L. enzymogenes, and their own regulons exhibited
      only a few loci that were regulated by both systems. These findings unveil for
      the first time new roles of the Rpf/DSF and DF signaling systems in secondary
      metabolite biosynthesis of L. enzymogenes. 

PMID- 23974133
TI  - Probing 3-hydroxyflavone for in vitro glycorandomization of flavonols by YjiC.
AB  - The glycosylation of five different flavonols, fisetin, quercetin, myricetin,
      kaempferol, and 3-hydroxyflavone, was achieved by applying YjiC. 3-Hydroxyflavone
      was selected as a probe for in vitro glycorandomization of all flavonols using
      diverse nucleotide diphosphate-d/l-sugars. This study unlocked the possibilities
      of the glycodiversification of flavonols and the generation of novel compounds as
      future therapeutics. 

PMID- 23974134
TI  - Development of a DNA microarray method for detection and identification of all 15
      distinct O-antigen forms of Legionella pneumophila.
AB  - Legionella is ubiquitous in many environments. At least 50 species and 70
      serogroups of the Gram-negative bacterium have been identified. Of the 50
      species, 20 are pathogenic, and Legionella pneumophila is responsible for the
      great majority (approximately 90%) of the Legionnaires' disease cases that occur.
      Furthermore, of the 15 L. pneumophila serogroups identified, O1 alone causes more
      than 84% of the Legionnaires' disease cases that occur worldwide. Rapid and
      reliable assays for the detection and identification of L. pneumophila in water,
      environmental, and clinical samples are in great demand. L. pneumophila bacteria
      are traditionally identified by their O antigens by immunological methods. We
      have recently developed an O serogroup-specific DNA microarray for the detection
      of all 15 distinct O-antigen forms of L. pneumophila, including serogroups O1 to
      O15. A total of 35 strains were used to verify the specificity of the microarray,
      including 15 L. pneumophila O-antigen standard reference strains and seven L.
      pneumophila clinical isolates as target strains, seven reference strains of other
      non-pneumophila Legionella species as closely related strains, and six non
      Legionella bacterial species as nonrelated strains. The detection sensitivity was
      1 ng of genomic DNA or 0.4 CFU/ml in water samples with filter enrichment and
      plate culturing. This study demonstrated that the microarray allows specific,
      sensitive, and reproducible detection of L. pneumophila serogroups. To the best
      of our knowledge, this is the first report of a microarray serotyping method for
      all 15 distinct O-antigen forms of L. pneumophila. 

PMID- 23974135
TI  - Occurrence and genetic diversity of Arcobacter butzleri in an artisanal dairy
      plant in Italy.
AB  - The present study aimed to investigate the presence, distribution, and
      persistence of Arcobacter spp. in an artisanal dairy plant and to test the
      isolates to determine their different genotypes in the processing plant and in
      foods. Samples were collected in an artisanal cheese factory on four occasions
      between October and December 2012. Food samples (raw milk, ricotta cheese,
      mozzarella cheese, and conditioning liquid), water samples, and environmental
      samples were analyzed by the culture method; isolates were identified by
      multiplex PCR and genotyped by pulsed-field gel electrophoresis (PFGE) analysis.
      Arcobacter butzleri was isolated from 29 out of 59 samples (46.6%), 22 of which
      were from environmental samples and 7 of which were from food samples. Cluster
      analysis divided the strains into 47 PFGE patterns: 14 PFGE clusters and 33
      unique types. Our findings indicate that the plant harbored numerous A. butzleri
      pulsotypes and that the manual cleaning and sanitation in the studied dairy plant
      do not effectively remove Arcobacter. The recurrent isolation of A. butzleri
      suggests that the environmental conditions in the dairy plant constitute a good
      ecological niche for the colonization of this microorganism. In some cases, the
      presence of indistinguishable strains isolated from the same facilities on
      different sampling days showed that these strains were persistent in the
      processing environment. 

PMID- 23974136
TI  - Distribution-based clustering: using ecology to refine the operational taxonomic
      unit.
AB  - 16S rRNA sequencing, commonly used to survey microbial communities, begins by
      grouping individual reads into operational taxonomic units (OTUs). There are two
      major challenges in calling OTUs: identifying bacterial population boundaries and
      differentiating true diversity from sequencing errors. Current approaches to
      identifying taxonomic groups or eliminating sequencing errors rely on sequence
      data alone, but both of these activities could be informed by the distribution of
      sequences across samples. Here, we show that using the distribution of sequences
      across samples can help identify population boundaries even in noisy sequence
      data. The logic underlying our approach is that bacteria in different populations
      will often be highly correlated in their abundance across different samples.
      Conversely, 16S rRNA sequences derived from the same population, whether slightly
      different copies in the same organism, variation of the 16S rRNA gene within a
      population, or sequences generated randomly in error, will have the same
      underlying distribution across sampled environments. We present a simple OTU
      calling algorithm (distribution-based clustering) that uses both genetic distance
      and the distribution of sequences across samples and demonstrate that it is more
      accurate than other methods at grouping reads into OTUs in a mock community.
      Distribution-based clustering also performs well on environmental samples: it is
      sensitive enough to differentiate between OTUs that differ by a single base pair
      yet predicts fewer overall OTUs than most other methods. The program can decrease
      the total number of OTUs with redundant information and improve the power of many
      downstream analyses to describe biologically relevant trends. 

PMID- 23974137
TI  - Design and optimization of short DNA sequences that can be used as 5' fusion
      partners for high-level expression of heterologous genes in Escherichia coli.
AB  - The 5' terminal nucleotide sequence of a gene is often a bottleneck in
      recombinant protein production. The ifn-alpha2bS gene is poorly expressed in
      Escherichia coli unless a translocation signal sequence (pelB) is fused to the 5'
      end of the gene. A combined in silico and in vivo analysis reported here further
      indicates that the ifn-alpha2bS 5' coding sequence is suboptimal for efficient
      gene expression. ifn-alpha2bS therefore presents a suitable model gene for
      describing properties of 5' fusions promoting expression. We show that short DNA
      sequences corresponding to the 5' end of the highly expressed celB gene, whose
      protein product is cytosolic, can functionally replace pelB as a 5' fusion
      partner for efficient ifn-alpha2bS expression. celB fusions of various lengths
      (corresponding to a minimum of 8 codons) led to more than 7- and 60-fold
      stimulation of expression at the transcript and protein levels, respectively.
      Moreover, the presence of a celB-based fusion partner was found to moderately
      reduce the decay rate of the corresponding transcript. The 5' fusions thus appear
      to act by enhancing translation, and bound ribosomes may accordingly contribute
      to increased mRNA stability and reduced mRNA decay. However, other effects, such
      as altered protein stability, cannot be excluded. We also developed an
      experimental protocol that enabled us to identify improved variants of the celB
      fusion, and one of these (celBD11) could be used to additionally increase ifn
      alpha2bS expression more than 4-fold at the protein level. Interestingly, celBD11
      also stimulated greater protein production of three other medically important
      human genes than the wild-type celB fragment. 

PMID- 23974138
TI  - Bimodular peptide synthetase SidE produces fumarylalanine in the human pathogen
      Aspergillus fumigatus.
AB  - The filamentous mold Aspergillus fumigatus causes invasive aspergillosis, a
      potentially life-threatening infectious disease, in humans. The sidE gene encodes
      a bimodular peptide synthetase and was shown previously to be strongly
      upregulated during initiation of murine lung infection. In this study, we
      characterized the two adenylation domains of SidE with the ATP
      [(32)P]pyrophosphate exchange assay in vitro, which identified fumarate and l
      alanine, respectively, as the preferred substrates. Using full-length holo-SidE,
      fumarylalanine (FA) formation was observed in vitro. Furthermore, FA was
      identified in A. fumigatus culture supernatants under inducing conditions, unless
      sidE was genetically inactivated. As FA is structurally related to established
      pharmaceutical products exerting immunomodulatory activity, this work may
      contribute to our understanding of the virulence of A. fumigatus. 

PMID- 23974139
TI  - Molecular and phenotypic characterization of Escherichia coli O26:H8 among
      diarrheagenic E. coli O26 strains isolated in Brazil.
AB  - Escherichia coli strains of serogroup O26 comprise two distinct groups of
      pathogens, characterized as enteropathogenic E. coli (EPEC) and enterohemorrhagic
      E. coli (EHEC). Among the several genes related to type III secretion system
      secreted effector proteins, espK was found to be highly specific for EHEC O26:H11
      and its stx-negative derivative strains isolated in European countries. E. coli
      O26 strains isolated in Brazil from infant diarrhea, foods, and the environment
      have consistently been shown to lack stx genes and are thus considered atypical
      EPEC. However, no further information related to their genetic background is
      known. Therefore, in this study, we aimed to discriminate and characterize these
      Brazilian O26 stx-negative strains by phenotypic, genetic, and biochemical
      approaches. Among 44 isolates confirmed to be O26 isolates, most displayed
      flagellar antigen H11 or H32. Out of the 13 nonmotile isolates, 2 tested positive
      for fliCH11, and 11 were fliCH8 positive. The identification of genetic markers
      showed that several O26:H11 and all O26:H8 strains tested positive for espK and
      could therefore be discriminated as EHEC derivatives. The presence of H8 among
      EHEC O26 and its stx-negative derivative isolates is described for the first
      time. The interaction of three isolates with polarized Caco-2 cells and with
      intestinal biopsy specimen fragments ex vivo confirmed the ability of the O26
      strains analyzed to cause attaching-and-effacing (A/E) lesions. The O26:H32
      strains, isolated mostly from meat, were considered nonvirulent. Knowledge of the
      virulence content of stx-negative O26 isolates within the same serotype helped to
      avoid misclassification of isolates, which certainly has important implications
      for public health surveillance. 

PMID- 23974140
TI  - Moderate prevalence of antimicrobial resistance in Escherichia coli isolates from
      lettuce, irrigation water, and soil.
AB  - Fresh produce is known to carry nonpathogenic epiphytic microorganisms. During
      agricultural production and harvesting, leafy greens can become contaminated with
      antibiotic-resistant pathogens or commensals from animal and human sources. As
      lettuce does not undergo any inactivation or preservation treatment during
      processing, consumers may be exposed directly to all of the (resistant) bacteria
      present. In this study, we investigated whether lettuce or its production
      environment (irrigation water, soil) is able to act as a vector or reservoir of
      antimicrobial-resistant Escherichia coli. Over a 1-year period, eight lettuce
      farms were visited multiple times and 738 samples, including lettuce seedlings
      (leaves and soil), soil, irrigation water, and lettuce leaves were collected.
      From these samples, 473 isolates of Escherichia coli were obtained and tested for
      resistance to 14 antimicrobials. Fifty-four isolates (11.4%) were resistant to
      one or more antimicrobials. The highest resistance rate was observed for
      ampicillin (7%), followed by cephalothin, amoxicillin-clavulanic acid,
      tetracycline, trimethoprim, and streptomycin, with resistance rates between 4.4
      and 3.6%. No resistance to amikacin, ciprofloxacin, gentamicin, or kanamycin was
      observed. One isolate was resistant to cefotaxime. Among the multiresistant
      isolates (n = 37), ampicillin and cephalothin showed the highest resistance
      rates, at 76 and 52%, respectively. E. coli isolates from lettuce showed higher
      resistance rates than E. coli isolates obtained from soil or irrigation water
      samples. When the presence of resistance in E. coli isolates from lettuce
      production sites and their resistance patterns were compared with the profiles of
      animal-derived E. coli strains, they were found to be the most comparable with
      what is found in the cattle reservoir. This may suggest that cattle are a
      potential reservoir of antimicrobial-resistant E. coli strains in plant primary
      production. 

PMID- 23974141
TI  - Mapping of heavy metal ion sorption to cell-extracellular polymeric substance
      mineral aggregates by using metal-selective fluorescent probes and confocal laser
      scanning microscopy.
AB  - Biofilms, organic matter, iron/aluminum oxides, and clay minerals bind toxic
      heavy metal ions and control their fate and bioavailability in the environment.
      The spatial relationship of metal ions to biomacromolecules such as extracellular
      polymeric substances (EPS) in biofilms with microbial cells and biogenic minerals
      is complex and occurs at the micro- and submicrometer scale. Here, we review the
      application of highly selective and sensitive metal fluorescent probes for
      confocal laser scanning microscopy (CLSM) that were originally developed for use
      in life sciences and propose their suitability as a powerful tool for mapping
      heavy metals in environmental biofilms and cell-EPS-mineral aggregates (CEMAs).
      The benefit of using metal fluorescent dyes in combination with CLSM imaging over
      other techniques such as electron microscopy is that environmental samples can be
      analyzed in their natural hydrated state, avoiding artifacts such as aggregation
      from drying that is necessary for analytical electron microscopy. In this
      minireview, we present data for a group of sensitive fluorescent probes highly
      specific for Fe(3+), Cu(2+), Zn(2+), and Hg(2+), illustrating the potential of
      their application in environmental science. We evaluate their application in
      combination with other fluorescent probes that label constituents of CEMAs such
      as DNA or polysaccharides and provide selection guidelines for potential
      combinations of fluorescent probes. Correlation analysis of spatially resolved
      heavy metal distributions with EPS and biogenic minerals in their natural,
      hydrated state will further our understanding of the behavior of metals in
      environmental systems since it allows for identifying bonding sites in complex,
      heterogeneous systems. 

PMID- 23974142
TI  - Stationary phase and nutrient levels trigger transcription of a genomic locus
      containing a novel peptide (TM1316) in the hyperthermophilic bacterium Thermotoga
      maritima.
AB  - The genome of the hyperthermophilic bacterium Thermotoga maritima encodes
      numerous putative peptides/proteins of 100 amino acids or less. While most of
      these open reading frames (ORFs) are transcribed during growth, their
      corresponding physiological roles are largely unknown. The onset of stationary
      phase in T. maritima was accompanied by significant morphological changes and
      upregulation of several ORFs located in the TM1298-TM1336 genome locus. This
      region contains putative HicAB toxin-antitoxin pairs, hypothetical proteins,
      radical S-adenosylmethionine (SAM) enzymes, and ABC transporters. Of particular
      note was the TM1315-TM1319 operon, which includes a putative 31-amino-acid
      peptide (TM1316) that was the most highly transcribed gene in the transcriptome
      during stationary phase. Antibodies directed against a synthetic version of
      TM1316 were used to track its production, which correlated closely with
      transcriptomic data. Immunofluorescence microscopy revealed that TM1316 was
      localized to the cell envelope and prominent in cell aggregates formed during
      stationary phase. The only functionally characterized locus with an organization
      similar to that of TM1315-TM1319 is in Bacillus subtilis, which contains
      subtilosin A, a cyclic peptide with Cys-to-alpha-carbon linkages that functions
      as an antilisterial bacteriocin. While the organization of TM1316 resembled that
      of the Bacillus peptide (e.g., in its number of amino acids and spacing of Cys
      residues), preparations containing high levels of TM1316 affected the growth of
      neither Thermotoga species nor Pyrococcus furiosus, a hyperthermophilic archaeon
      isolated from the same locale as T. maritima. Several other putative Cys-rich
      peptides could be identified in the TM1298-TM1336 locus, and while their roles
      are also unclear, they merit examination as potential antimicrobial agents in
      hyperthermophilic biotopes. 

PMID- 23974143
TI  - Streptomycin application has no detectable effect on bacterial community
      structure in apple orchard soil.
AB  - Streptomycin is commonly used to control fire blight disease on apple trees.
      Although the practice has incited controversy, little is known about its
      nontarget effects in the environment. We investigated the impact of aerial
      application of streptomycin on nontarget bacterial communities in soil beneath
      streptomycin-treated and untreated trees in a commercial apple orchard. Soil
      samples were collected in two consecutive years at 4 or 10 days before spraying
      streptomycin and 8 or 9 days after the final spray. Three sources of microbial
      DNA were profiled using tag-pyrosequencing of 16S rRNA genes: uncultured bacteria
      from the soil (culture independent) and bacteria cultured on unamended or
      streptomycin-amended (15 MUg/ml) media. Multivariate tests for differences in
      community structure, Shannon diversity, and Pielou's evenness test results showed
      no evidence of community response to streptomycin. The results indicate that use
      of streptomycin for disease management has minimal, if any, immediate effect on
      apple orchard soil bacterial communities. This study contributes to the profile
      of an agroecosystem in which antibiotic use for disease prevention appears to
      have minimal consequences for nontarget bacteria. 

PMID- 23974144
TI  - Characterization of a potential Listeria monocytogenes virulence factor
      associated with attachment to fresh produce.
AB  - A study to determine the attachment of L. monocytogenes serotype 4b strain F2365
      on vegetables and fruits was conducted. In an initial study, we screened 32 genes
      encoding surface proteins and lipases of the strain to find highly expressed
      genes on lettuce leaves. The results showed that transcription levels of
      LMOf2365_0413, LMOf2365_0498, LMOf2365_0859, LMOf2365_2052, and LMOf2365_2812
      were significantly upregulated on lettuce leaves. In silico analysis showed that
      LMOf2365_0859 contains a putative cellulose binding domain. Thus, we hypothesized
      that this gene may be involved in an attachment to vegetables, and named it lcp
      (gene encoding Listeria cellulose binding protein [LCP]). lcp mutant (Deltalcp)
      and lcp complement (F2365::pMAD::cat::lcp) strains were generated by homologous
      recombination. The abilities of a wild-type (WT) strain, the Deltalcp strain, and
      the complemented strain to attach to lettuce leaves were evaluated, which
      indicated that the attachment of the Deltalcp strain to lettuce was significantly
      less than that of the WT and the complemented strains. Similar results were
      observed for baby spinach and cantaloupe. Fluorescence microscopy and field
      emission scanning microscopy analysis further supported these findings. The
      binding of L. monocytogenes to cellulose was determined using cellulose acetate
      coated plates. The results showed that a binding ability of the Deltalcp strain
      was significantly lower than that of the wild type. Combined, these results
      strongly suggest that LCP plays an important role in an attachment to vegetables
      and fruits. 

PMID- 23974145
TI  - Engineered Escherichia coli with periplasmic carbonic anhydrase as a biocatalyst
      for CO2 sequestration.
AB  - Carbonic anhydrase is an enzyme that reversibly catalyzes the hydration of carbon
      dioxide (CO2). It has been suggested recently that this remarkably fast enzyme
      can be used for sequestration of CO2, a major greenhouse gas, making this a
      promising alternative for chemical CO2 mitigation. To promote the economical use
      of enzymes, we engineered the carbonic anhydrase from Neisseria gonorrhoeae
      (ngCA) in the periplasm of Escherichia coli, thereby creating a bacterial whole
      cell catalyst. We then investigated the application of this system to CO2
      sequestration by mineral carbonation, a process with the potential to store large
      quantities of CO2. ngCA was highly expressed in the periplasm of E. coli in a
      soluble form, and the recombinant bacterial cell displayed the distinct ability
      to hydrate CO2 compared with its cytoplasmic ngCA counterpart and previously
      reported whole-cell CA systems. The expression of ngCA in the periplasm of E.
      coli greatly accelerated the rate of calcium carbonate (CaCO3) formation and
      exerted a striking impact on the maximal amount of CaCO3 produced under
      conditions of relatively low pH. It was also shown that the thermal stability of
      the periplasmic enzyme was significantly improved. These results demonstrate that
      the engineered bacterial cell with periplasmic ngCA can successfully serve as an
      efficient biocatalyst for CO2 sequestration. 

PMID- 23974146
TI  - Insertion of endocellulase catalytic domains into thermostable consensus ankyrin
      scaffolds: effects on stability and cellulolytic activity.
AB  - Degradation of cellulose for biofuels production holds promise in solving
      important environmental and economic problems. However, the low activities (and
      thus high enzyme-to-substrate ratios needed) of hydrolytic cellulase enzymes,
      which convert cellulose into simple sugars, remain a major barrier. As a
      potential strategy to stabilize cellulases and enhance their activities, we have
      embedded cellulases of extremophiles into hyperstable alpha-helical consensus
      ankyrin domain scaffolds. We found the catalytic domains CelA (CA, GH8;
      Clostridium thermocellum) and Cel12A (C12A, GH12; Thermotoga maritima) to be
      stable in the context of the ankyrin scaffold and to be active against both
      soluble and insoluble substrates. The ankyrin repeats in each fusion are folded,
      although it appears that for the C12A catalytic domain (CD; where the N and C
      termini are distant in the crystal structure), the two flanking ankyrin domains
      are independent, whereas for CA (where termini are close), the flanking ankyrin
      domains stabilize each other. Although the activity of CA is unchanged in the
      context of the ankyrin scaffold, the activity of C12A is increased between 2- and
      6-fold (for regenerated amorphous cellulose and carboxymethyl cellulose
      substrates) at high temperatures. For C12A, activity increases with the number of
      flanking ankyrin repeats. These results showed ankyrin arrays to be a promising
      scaffold for constructing designer cellulosomes, preserving or enhancing
      enzymatic activity and retaining thermostability. This modular architecture will
      make it possible to arrange multiple cellulase domains at a precise spacing
      within a single polypeptide, allowing us to search for spacings that may optimize
      reactivity toward the repetitive cellulose lattice. 

PMID- 23974148
TI  - Treatment of congenital clubfoot with the Ponseti method: the parents'
      perspective.
AB  - This study aimed to analyze the perceptions of parents of children with clubfoot
      regarding the Ponseti method of treatment, and identify aspects of treatment that
      families found most difficult. Thirty families of children with clubfoot were
      treated with the Ponseti method over a 4-year period, and questionnaires were
      distributed at the conclusion of treatment. The most difficult components of
      treatment were identified. However, these challenges did not impact treatment
      outcome negatively. We hypothesize that a strong physician-patient relationship
      and high levels of parental education may decrease perceived difficulties of
      treatment with the Ponseti method. 

PMID- 23974147
TI  - Small molecule Plasmodium FKBP35 inhibitor as a potential antimalaria agent.
AB  - Malaria parasite strains have emerged to tolerate the therapeutic effects of the
      prophylactics and drugs presently available. This resistance now poses a serious
      challenge to researchers in the bid to overcome malaria parasitic infection.
      Recent studies have shown that FK520 and its analogs inhibit malaria parasites
      growth by binding to FK506 binding proteins (FKBPs) of the parasites. Structure
      based drug screening efforts based on three-dimensional structural information of
      FKBPs from Plasmodium falciparum led us to identify new chemical entities that
      bind to the parasite FKBP35 and inhibit its growth. Our experimental results
      verify that this novel compound (D44) modulate the PPIase activity of Plasmodium
      FKBP35 and demonstrate the stage-specific growth inhibition of Plasmodium
      falciparum strains. Here, we present the X-ray crystallographic structures of
      FK506 binding domains (FKBDs) of PfFKBP35 and PvFKBP35 in complex with the newly
      identified inhibitor providing molecular insights into its mode of action. 

PMID- 23974149
TI  - Endometrial cancer with endobronchial metastasis.

PMID- 23974150
TI  - High resolution direction of arrival (DOA) estimation based on improved
      orthogonal matching pursuit (OMP) algorithm by iterative local searching.
AB  - DOA (Direction of Arrival) estimation is a major problem in array signal
      processing applications. Recently, compressive sensing algorithms, including
      convex relaxation algorithms and greedy algorithms, have been recognized as a
      kind of novel DOA estimation algorithm. However, the success of these algorithms
      is limited by the RIP (Restricted Isometry Property) condition or the mutual
      coherence of measurement matrix. In the DOA estimation problem, the columns of
      measurement matrix are steering vectors corresponding to different DOAs. Thus, it
      violates the mutual coherence condition. The situation gets worse when there are
      two sources from two adjacent DOAs. In this paper, an algorithm based on OMP
      (Orthogonal Matching Pursuit), called ILS-OMP (Iterative Local Searching
      Orthogonal Matching Pursuit), is proposed to improve DOA resolution by Iterative
      Local Searching. Firstly, the conventional OMP algorithm is used to obtain
      initial estimated DOAs. Then, in each iteration, a local searching process for
      every estimated DOA is utilized to find a new DOA in a given DOA set to further
      decrease the residual. Additionally, the estimated DOAs are updated by
      substituting the initial DOA with the new one. The simulation results demonstrate
      the advantages of the proposed algorithm. 

PMID- 23974152
TI  - Cognitive radio wireless sensor networks: applications, challenges and research
      trends.
AB  - A cognitive radio wireless sensor network is one of the candidate areas where
      cognitive techniques can be used for opportunistic spectrum access. Research in
      this area is still in its infancy, but it is progressing rapidly. The aim of this
      study is to classify the existing literature of this fast emerging application
      area of cognitive radio wireless sensor networks, highlight the key research that
      has already been undertaken, and indicate open problems. This paper describes the
      advantages of cognitive radio wireless sensor networks, the difference between ad
      hoc cognitive radio networks, wireless sensor networks, and cognitive radio
      wireless sensor networks, potential application areas of cognitive radio wireless
      sensor networks, challenges and research trend in cognitive radio wireless sensor
      networks. The sensing schemes suited for cognitive radio wireless sensor networks
      scenarios are discussed with an emphasis on cooperation and spectrum access
      methods that ensure the availability of the required QoS. Finally, this paper
      lists several open research challenges aimed at drawing the attention of the
      readers toward the important issues that need to be addressed before the vision
      of completely autonomous cognitive radio wireless sensor networks can be
      realized. 

PMID- 23974151
TI  - Identification of capacitive MEMS accelerometer structure parameters for human
      body dynamics measurements.
AB  - Due to their small size, low weight, low cost and low energy consumption, MEMS
      accelerometers have achieved great commercial success in recent decades. The aim
      of this research work is to identify a MEMS accelerometer structure for human
      body dynamics measurements. Photogrammetry was used in order to measure possible
      maximum accelerations of human body parts and the bandwidth of the digital
      acceleration signal. As the primary structure the capacitive accelerometer
      configuration is chosen in such a way that sensing part measures on all three
      axes as it is 3D accelerometer and sensitivity on each axis is equal. Hill
      climbing optimization was used to find the structure parameters. Proof-mass
      displacements were simulated for all the acceleration range that was given by the
      optimization problem constraints. The final model was constructed in Comsol
      Multiphysics. Eigenfrequencies were calculated and model's response was found,
      when vibration stand displacement data was fed into the model as the base
      excitation law. Model output comparison with experimental data was conducted for
      all excitation frequencies used during the experiments. 

PMID- 23974153
TI  - Polycarbonate as an elasto-plastic material model for simulation of the
      microstructure hot imprint process.
AB  - The thermal imprint process of polymer micro-patterning is widely applied in
      areas such as manufacturing of optical parts, solar energy, bio-mechanical
      devices and chemical chips. Polycarbonate (PC), as an amorphous polymer, is often
      used in thermoforming processes because of its good replication characteristics.
      In order to obtain replicas of the best quality, the imprint parameters (e.g.,
      pressure, temperature, time, etc.) must be determined. Therefore finite element
      model of the hot imprint process of lamellar periodical microstructure into PC
      has been created using COMSOL Multiphysics. The mathematical model of the hot
      imprint process includes three steps: heating, imprinting and demolding. The
      material properties of amorphous PC strongly depend on the imprint temperature
      and loading pressure. Polycarbonate was modelled as an elasto-plastic material,
      since it was analyzed below the glass transition temperature. The hot imprint
      model was solved using the heat transfer and the solid stress-strain application
      modes with thermal contact problem between the mold and polycarbonate. It was
      used for the evaluation of temperature and stress distributions in the
      polycarbonate during the hot imprint process. The quality of the replica, by
      means of lands filling ratio, was determined as well. 

PMID- 23974154
TI  - Finger vein recognition with personalized feature selection.
AB  - Finger veins are a promising biometric pattern for personalized identification in
      terms of their advantages over existing biometrics. Based on the spatial pyramid
      representation and the combination of more effective information such as gray,
      texture and shape, this paper proposes a simple but powerful feature, called
      Pyramid Histograms of Gray, Texture and Orientation Gradients (PHGTOG). For a
      finger vein image, PHGTOG can reflect the global spatial layout and local details
      of gray, texture and shape. To further improve the recognition performance and
      reduce the computational complexity, we select a personalized subset of features
      from PHGTOG for each subject by using the sparse weight vector, which is trained
      by using LASSO and called PFS-PHGTOG. We conduct extensive experiments to
      demonstrate the promise of the PHGTOG and PFS-PHGTOG, experimental results on our
      databases show that PHGTOG outperforms the other existing features. Moreover, PFS
      PHGTOG can further boost the performance in comparison with PHGTOG. 

PMID- 23974155
TI  - Heavy-metal content and oxidative damage in Hypsiboas faber: the impact of coal
      mining pollutants on amphibians.
AB  - It has been identified worldwide that amphibians are experiencing massive
      population declines. This decrease could be further enhanced by the exposure of
      amphibians to pollutants, which would enhance reactive oxygen species production
      and cause subsequent alterations in oxidant defense levels. The present study was
      aimed at understanding the impact of mineral coal on amphibians. For this
      purpose, chemical elemental contents and oxidative stress indexes in Hypsiboas
      faber from coal-mining areas and in an unpolluted area in the Catarinense Coal
      Basin, Brazil, were assessed. The highest contents of sulfur, chlorine, iron,
      zinc, and bromine were registered in specimens from the coal-mining area, whereas
      the highest contents of potassium calcium, and silicon were registered in
      specimens from the control area. It was found that there was a significant
      increase (p < 0.05) in the activity of super oxide dismutase (SOD) and
      glutathione peroxidase (GPx) in the animals from the coal-mining area, whereas
      the level of catalase showed no differences between the animal groups. The levels
      of TBARS showed no differences between the tested groups. However, carbonylation
      decreased significantly (p < 0.05) in animals from the coal-mining area, and
      there was a significant increase (p < 0.05) in the formation of total thiols in
      animals from the coal-mining area. In conclusion, the antioxidant system of H.
      faber is sensitive to pollutants present in coal-mining wastes, and its SOD and
      GPx activity may be a potential biomarker for monitoring the level of
      contaminants in the environment. 

PMID- 23974156
TI  - A novel method to directionally stabilize enzymes together with redox mediators
      by electrodeposition.
AB  - This paper depicts a novel method to directionally stabilize enzymes together
      with redox mediators by electrodeposition. Chitosan was used as a stabilizing
      matrix. By electrochemical removal of local H(+), chitosan close to working
      electrode became locally insoluble, and enzymes and redox mediators in chitosan
      were stabilized. The microelectrode on home-made microelectrode array (MEA)
      served as the working electrode. Three model enzymes--horseradish peroxidase
      (HRP), glucose oxidase (GOD), and glutamate oxidase (GlOD)--were used to
      fabricate different biosensors, and the redox mediator model was a
      poly(vinylpyridine) complex of Os(bpy)2Cl and a diepoxide (PVP-Os). Biosensors
      fabricated by the method exhibited very high performance. For HRP biosensor
      fabricated by this method, the sensitivity was 5.274 nA MUM(-1) mm(-2), with
      linear detection range (LDR) of 2-220 MUM and limit of detection (LOD) of 1 MUM
      (S/N=3); for GOD biosensor, the sensitivity was 2.65 nA MUM(-1) mm(-2), with LDR
      of 4-500 MUM and LOD of 2 MUM (S/N=3); for GlOD biosensor, the sensitivity was
      0.33 nA MUM(-1)mm(-2), with LDR of 4-500 MUM and LOD of 2 MUM (S/N=3). Since this
      method is very simple and especially suitable for directionally introducing
      enzymes and redox mediators onto microelectrode without contaminating other sites
      in the same microenvironment, it could be used for fabricating in vivo or in
      vitro 2nd generation biosensors in MUm-scale, especially in neuroscience.

PMID- 23974157
TI  - Potentiometric glucose biosensor based on core-shell Fe3O4-enzyme-polypyrrole
      nanoparticles.
AB  - Core-shell Fe3O4-enzyme-polypyrrole (Ppy) nanoparticles with excellent magnetism
      and conductivity were successfully prepared via the surface modification and
      enzyme self-encapsulation within Ppy. A novel potentiometric glucose biosensor
      has been constructed by effectively attaching the proposed Fe3O4-enzyme-Ppy
      nanoparticles to the surface of the magnetic glassy carbon electrode (MGCE). The
      optimum biosensing conditions could be provided with polymerization time of
      pyrrole for 6h and 0.42 mg immobilization amount of Fe3O4-enzyme-Ppy
      nanoparticles on MGCE. The performance of the developed glucose biosensor was
      evaluated and the results indicated that a sensitive glucose biosensor could be
      fabricated. The obtained glucose biosensor presents shorter response time (6 s),
      wider linear range (0.5 MUM to 34 mM), lower limit of detection (LOD, 0.3 MUM),
      high-selectivity monitoring of glucose and good stability (with about 98.1% of
      the initial response signal retained after 20 days). The analytical application
      of the glucose biosensor confirms the feasibility of glucose detection in serum
      sample.

PMID- 23974158
TI  - Whole-cell Escherichia coli-based bio-sensor assay for dual zinc oxide
      nanoparticle toxicity mechanisms.
AB  - A whole-cell biosensor assay for dual ZnO nanoparticle toxicity mechanisms has
      been developed based on the transcriptional response of Escherichia coli to: (1)
      Zn(2+) from ZnO nanoparticle dissolution with genes zntA (Zn(2+) efflux) and
      znuABC (Zn(2+) uptake); and (2) redox stress from ZnO nanoparticle photo-electron
      production under ultraviolet light with genes soxS and katG. Both processes occur
      in a dispersion of ZnO nanoparticles leading to toxicity. ZnO nanoparticle
      dissolution was measured independently by ICP-MS and photo-radical generation was
      confirmed by the stochiometric reduction of the redox dye, 2, 6
      dichloroindolphenol (DCPIP). The whole-cell biosensor can detect both toxicity
      mechanisms and is a species-specific assay capable of discriminating between ZnO
      nanoparticles and the Zn(2+) dissolution product.

PMID- 23974159
TI  - Microfluidic biosensor for the detection of DNA by fluorescence enhancement and
      the following streptavidin detection by fluorescence quenching.
AB  - We reported an optical DNA/protein microfluidic sensor which consists of single
      stranded (ss) DNA-Cy3 probes on gold surface and simple line-shape microfluidic
      channel. These ssDNA-Cy3 probes with random sequence in bulk solution or on gold
      surface exhibits fluorescence enhancement after binding with complementary ssDNA
      (cssDNA) targets. Particularly it did not require complicated design or hairpin
      like stem-loop conformation, which made it easier to be made and applied in
      analytes detection by fluorescence switching techniques. Using ssDNA-cy3 probes
      attached on gold surface in a microfluidic channel, strong fluorescence
      enhancement was measured by ssDNA with cssDNA binding or ssDNA with cssDNA-biotin
      binding. The following introduction of streptavidin resulted in fluorescence
      quenching (fluorescence decrease) because of the binding of hybridized DNA-biotin
      with streptavidin. This sensor showed strong affinity and high sensitivity toward
      the streptavidin, the minimum detectable concentration for streptavidin was 1 pM,
      equating to an absolute detection limit of 60 amol in this microfluidic channel.
      Microfluidic channel height and flow rate is optimized to increase surface
      reaction efficiency and fluorescence switching efficiency. In contrast to
      previously reported optical molecular beacon approach, this sensor can be used
      not only for the detection of cssDNA target, but also for the detection of
      streptavidin. This microfluidic sensor offers the promise of analyzing kinds of
      molecular targets or immunoreactions.

PMID- 23974160
TI  - Molecularly imprinted quartz crystal microbalance sensor based on poly(o
      aminothiophenol) membrane and Au nanoparticles for ractopamine determination.
AB  - A molecularly imprinted quartz crystal microbalance (QCM) sensor for ractopamine
      (RAC) detection was developed by electrodepositing a poly-o-aminothiophenol
      membrane on an Au electrode surface modified by self-assembled Au nanoparticles
      (AuNPs). The modified electrodes were characterized by cyclic voltammetry,
      electrochemical impedance spectroscopy and scanning electron microscopy. This
      molecularly imprinted QCM sensor showed good frequency response in RAC binding
      measurements and the introduction of AuNPs demonstrated performance improvements.
      Frequency shifts were found to be proportional to concentration of RAC in the
      range of 2.5*10(-6) to 1.5*10(-4) mol L(-1) with a detection limit of 1.17*10(-6)
      mol L(-1) (S/N=3). The sensor showed a good selective affinity for RAC
      (selectivity coefficient >3) compared with similar molecules and good
      reproducibility and long-term stability. This research has combined the
      advantages of high specific surface area of AuNPs, high selectivity from
      molecularly imprinted electrodeposited membrane and high sensitivity from quartz
      crystal microgravimetry. In addition, the modified electrode sensor was
      successfully applied to determine RAC residues in spiked swine feed samples with
      satisfactory recoveries ranging from 87.7 to 95.2%.

PMID- 23974161
TI  - Target-induced structure switching of hairpin aptamers for label-free and
      sensitive fluorescent detection of ATP via exonuclease-catalyzed target recycling
      amplification.
AB  - In this work, we described the development of a new label-free, simple and
      sensitive fluorescent ATP sensing platform based on exonuclease III (Exo III)
      catalyzed target recycling (ECTR) amplification and SYBR Green I indicator. The
      hairpin aptamer probes underwent conformational structure switching and re
      configuration in the presence of ATP, which led to catalytic cleavage of the re
      configured aptamers by Exo III to release ATP and to initiate the ECTR process.
      Such ECTR process resulted in the digestion of a significant number of the
      hairpin aptamer probes, leading to much less intercalation of SYBR Green I to the
      hairpin stems and drastic suppression of the fluorescence emission for sensitive
      ATP detection down to the low nanomolar level. Due to the highly specific
      affinity bindings between aptamers and ATP, the developed method exhibited
      excellent selectivity toward ATP against other analogous molecules. Besides, our
      ATP sensing approach used un-modified aptamer probes and could be performed in a
      "mix-and-detect" fashion in homogenous solutions. All these distinct advantages
      of the developed method thus made it hold great potential for the development of
      simple and robust sensing strategies for the detection of other small molecules. 

PMID- 23974162
TI  - Sevoflurane and isoflurane monoanesthesia abolished the phrenic long-term
      facilitation in rats.
AB  - Phrenic long-term facilitation (pLTF) is a form of respiratory plasticity,
      manifested by prolonged increase in peak amplitude of phrenic nerve activity
      (PNA) after episodes of acute intermittent hypoxia (AIH). The aim was to
      investigate the effects of sevoflurane and isoflurane monoanesthesia at
      equipotent anesthetic doses on the expression of amplitude pLTF. Experiments were
      performed on Sprague-Dawley anesthetized, vagotomized, and mechanically
      ventilated rats. Two experimental groups, sevoflurane and isoflurane, and a
      control group (urethane-anesthetized) were formed. Peak amplitude of phrenic
      nerve activity, respiratory frequency and breathing rhythm parameters (Ti,
      inspiratory duration; Te, expiratory duration; and Ttot, total respiratory time
      duration) were analyzed during hypoxic episodes, and at 15, 30, and 60min after
      the last hypoxic episode. In the control group average PNA increased by 173.03+/
      70.16% (p<0.001), at 60min after the last hypoxic episode compared to baseline
      values. Therefore amplitude pLTF was induced. In the sevoflurane and isoflurane
      groups PNA failed to increase, and in fact decreased by 15.79+/-15.18% and
      31.00+/-11.00%, respectively (p>0.05). Amplitude pLTF was abolished during
      sevoflurane and isoflurane monoanesthesia. 

PMID- 23974163
TI  - High capacitive performance of flexible and binder-free graphene-polypyrrole
      composite membrane based on in situ reduction of graphene oxide and self
      assembly.
AB  - Exploiting flexible and binder-free electrode materials is of importance for the
      fast development of smart supercapacitor devices. A simple and effective strategy
      is demonstrated to fabricate a flexible composite membrane of reduced graphene
      oxide and polypyrrole nanowire (RGO-PPy) via in situ reduction of graphene oxide
      and self-assembly. More importantly, the shape and thickness of the membrane can
      be reasonably controlled by varying either the concentration of GO and PPy
      nanowires or the filtration volume. By direct coupling of two membrane
      electrodes, symmetric supercapacitors can be fabricated without the use of a
      binder and conductive additive. The supercapacitor is able to offer large areal
      capacitance (175 mF cm(-2)) and excellent cycling stability (~93% capacitance
      retention after 5000 charge-discharge cycles), thanks to the synergic integration
      between RGO sheets and PPy nanowires and the unique self-assembled porous
      structure.

PMID- 23974164
TI  - Ozone distribution in remote ecologically vulnerable terrain of the southern
      Sierra Nevada, CA.
AB  - Ozone concentration spatial patterns remain largely uncharacterized across the
      extensive wilderness areas of the Sierra Nevada, CA, despite being downwind of
      major pollution sources. These natural areas, including four national parks and
      four national forests, contain forest species that are susceptible to ozone
      injury. Forests stressed by ozone are also more vulnerable to other agents of
      mortality, including insects, pathogens, climate change, and ultimately fire.
      Here we analyze three years of passive ozone monitor data from the southern
      Sierra Nevada and interpolate landscape-scale spatial and temporal patterns
      during the summer-through-fall high ozone concentration period. Segmentation
      analysis revealed three types of ozone exposure sub-regions: high, low, and
      variable. Consistently high ozone exposure regions are expected to be most
      vulnerable to forest mortality. One high exposure sub-region has been documented
      elsewhere as being further vulnerable to increased drought and fire potential.
      Identifying such hot-spots of forest vulnerability has utility for prioritizing
      management. 

PMID- 23974165
TI  - Sediment pore water distribution coefficients of PCB congeners in enriched black
      carbon sediment.
AB  - More than 2300 sediment pore water distribution coefficients (KPCBi ds) of 93
      polychlorinated biphenyls (PCBs) were measured and modeled from sediments from
      Indiana Harbor and Ship Canal. KPCBi ds were calculated from previously reported
      bulk sediment values and newly analyzed pore water. PCBs in pore waters were
      measured using SPME PDMS-fiber and ?PCB ranged from 41 to 1500 ng L(-1). The
      resulting KPCBi ds were ~1 log unit lower in comparison to other reported values.
      A simple model for the KPCBi d consisted of the product of the organic carbon
      fraction and the octanol-water partition coefficient and provided an excellent
      prediction for the measured values, with a mean square error of 0.09 +/- 0.06.
      Although black carbon content is very high in these sediments and was expected to
      play an important role in the distribution of PCBs, no improvement was obtained
      when a two-carbon model was used.

PMID- 23974166
TI  - Space and time resolved monitoring of airborne particulate matter in proximity of
      a traffic roundabout in Sweden.
AB  - Concerns over exposure to airborne particulate matter (PM) are on the rise.
      Currently monitoring of PM is done on the basis of interpolating a mass of PM by
      volume (MUg/m(3)) but has the drawback of not taking the chemical nature of PM
      into account. Here we propose a method of collecting PM at its emission source
      and employing automated analysis with scanning electron microscopy associated
      with EDS-analysis together with light scattering to discern the chemical
      composition, size distribution, and time and space resolved structure of PM
      emissions in a heavily trafficated roundabout in Sweden. Multivariate methods
      (PCA, ANOVA) indicate that the technogenic marker Fe follows roadside dust in
      spreading from the road, and depending on time and location of collection, a
      statistically significant difference can be seen, adding a useful tool to the
      repertoire of detailed PM monitoring and risk assessment of local emission
      sources. 

PMID- 23974167
TI  - Adverse effects induced by ecgonine methyl ester to the zebra mussel: a
      comparison with the benzoylecgonine.
AB  - Cocaine and its metabolites are the prevalent psychotropic substances in aquatic
      environment. However, to date the knowledge on their adverse effects to non
      target organisms is inadequate. The aims of this study were to investigate sub
      lethal effects induced by the ecgonine methyl ester (EME) to the freshwater
      bivalve Dreissena polymorpha and to compare its toxicity to that by
      benzoylecgonine (BE), the other main cocaine metabolite. EME sub-lethal effects
      were investigated by 14 days in-vivo exposures and a multi-biomarker approach.
      Slight variations in biomarker responses were found at 0.15 MUg/L treatment. 0.5
      MUg/L EME treatment induced destabilization of lysosome membranes, an overall
      inactivation of defense enzymes, increases in lipid peroxidation, protein
      carbonylation and DNA fragmentation, but no variations in fixed genetic damage.
      The use of a biomarker response index (BRI) showed that at 0.5 MUg/L both cocaine
      metabolites had the same toxicity to zebra mussels specimens.

PMID- 23974168
TI  - Study of molecularly imprinted solid-phase extraction of gonyautoxins 2,3 in the
      cultured dinoflagellate Alexandrium tamarense by high-performance liquid
      chromatography with fluorescence detection.
AB  - A highly selective sample cleanup procedure combined with molecularly imprinted
      solid-phase extraction (MISPE) was developed for the isolation of gonyautoxins
      2,3 (GTX2,3) from Alexandrium tamarense sample. The molecularly imprinted polymer
      microspheres (MIPMs) were prepared by suspension polymerization using caffeine as
      the dummy template molecule, methacrylic acid as the functional monomer, ethylene
      glycol dimethacrylate as the cross-linker and polyvinyl alcohol as the dispersive
      reagent. The polymer microspheres were used as a selective sorbent for the solid
      phase extraction of gonyautoxins 2,3. An off-line MISPE method followed by high
      performance liquid chromatography (HPLC) with fluorescence detection for the
      analysis of gonyautoxins 2,3 was established. Finally, the extract samples from
      Alexandrium tamarense were analyzed. The results showed the imprinted polymer
      microspheres exhibited high affinity and selectivity for gonyautoxins 2,3. The
      interference matrix in the extract were obviously cleaned by MISPE and the
      extraction efficiency of gonyautoxins 2,3 in the sample ranged from 81.74% to
      85.86%. 

PMID- 23974169
TI  - Coupling gold nanoparticles to silica nanoparticles through disulfide bonds for
      glutathione detection.
AB  - Advances in the controlled assembly of nanoscale building blocks have resulted in
      functional devices which can find applications in electronics, biomedical
      imaging, drug delivery etc. In this study, novel covalent nanohybrid materials
      based upon [Ru(bpy)3](2+)-doped silica nanoparticles (SiNPs) and gold
      nanoparticles (AuNPs), which could be conditioned as OFF-ON probes for
      glutathione (GSH) detection, were designed and assembled in sequence, with the
      disulfide bonds as the bridging elements. The structural and optical properties
      of the nanohybrid architectures were characterized using transmission electron
      microscopy, UV-vis spectroscopy and fluorescence spectroscopy, respectively. Zeta
      potential measurements, x-ray photoelectron spectroscopy and Fourier transform
      infrared spectroscopy were employed to monitor the reaction processes of the
      SiNPs-S-S-COOH and SiNPs-S-S-AuNPs synthesis. It was found that the covalent
      nanohybrid architectures were fluorescently dark (OFF state), indicating that
      SiNPs were effectively quenched by AuNPs. The fluorescence of the OFF-ON probe
      was resumed (ON state) when the bridge of the disulfide bond was cleaved by
      reducing reagents such as GSH. This work provides a new platform and strategy for
      GSH detection using covalent nanohybrid materials. 

PMID- 23974170
TI  - Innervation of developing and adult organs.

PMID- 23974171
TI  - Heparin-functionalized thermoresponsive surface: a versatile cell culture
      substrate for regulating multivalent affinity binding with heparin-binding
      proteins by temperature changes.
AB  - Temperature-dependent regulation of affinity binding between bioactive ligands
      and their cell membrane receptors is an attractive approach for the dynamic
      control of cellular adhesion, proliferation, migration, differentiation, and
      signal transduction. Covalent conjugation of bioactive ligands onto
      thermoresponsive poly(N-isopropylacrylamide) (PIPAAm)-grafted surfaces
      facilitates the modulation of one-on-one affinity binding between bioactive
      ligands and cellular receptors by changing temperature. For the dynamic control
      of the multivalent affinity binding between heparin and heparin-binding proteins,
      thermoresponsive cell culture surface modified with heparin, which interacts with
      heparin-binding proteins such as basic fibroblast growth factor (bFGF), has been
      proposed. Heparin-functionalized thermoresponsive cell culture surface induces
      (1) the multivalent affinity binding of bFGF in active form and (2) accelerating
      cell sheet formation in the state of shrunken PIPAAm chains at 37 degrees C. By
      lowering temperature to 20 degrees C, the affinity binding between bFGF and
      immobilized heparin is reduced with increasing the mobility of heparin and the
      swollen PIPAAm chains, leading to the detachment of cultured cells. Therefore,
      heparin-functionalized thermoresponsive cell culture surface was able to enhance
      cell proliferation and detach confluent cells as a contiguous cell sheet by
      changing temperature. A cell cultivation system using heparin-functionalized
      thermoresponsive cell culture surface is versatile for immobilizing other heparin
      binding proteins such as vascular endothelial growth factor, fibronectin,
      antithrombin III, and hepatocyte growth factor, etc. for tuning the adhesion,
      growth, and differentiation of various cell species. 

PMID- 23974172
TI  - Adaptive inflammatory microenvironment for cell-based regeneration in ischemic
      cardiovascular disease.
AB  - Cell-based therapy has emerged to be a promising strategy for alleviating the
      heavy burden of ischemic cardiovascular disease for nearly two decades, despite a
      variety of pending questions about its availability and efficacy. One question is
      whether and how the cells behave for regeneration in vivo, which could be limited
      or potentiated by the inflammatory microenvironment following myocardial
      infarction or critical limb ischemia. To this end, we hypothesize that the
      "adaptive inflammatory microenvironment" is pertinent to the cell-based
      regeneration, and make a brief comment on it based upon recent evidence. 

PMID- 23974173
TI  - Development of three dimensional culture and expression of integrin heterodimers
      in human embryonic stem cells.
AB  - Extensive effort has been made to develop a three-dimensional (3D) system for the
      culture of pluripotent stem cells in human and model animals, which yields lots
      of benefits for monitoring cell-to-cell or cell-to-environment interaction and
      for suggesting alternative materials for clinical cases. Initial study using
      animal model moved toward supporting embryonic stem cells (ESCs) self-renewal in
      a synthetic scaffold conjugated with suitable peptide motifs. As results, the
      feeder-free, 3D acellular niche consisting of vinyl sulfone (VS)-functionalized
      polyethylene glycol (PEG)-based hydrogel binding with extracellular matrix
      analogs could support ESC self-renewal, but main stemness signals were switched
      in the 3D environment. We employed this PEG-based hydrogel for 3D culture of
      human ESCs and further adjustment of hydrogel constituent made it possible to
      support self-renewal of three ESC lines. In this study, we examined
      transcriptional and translational activity of integrin heterodimers for
      optimizing the 3D system by using peptide motifs and subsequently elucidated that
      transcription and translation of integrin alpha 5beta 1, alpha 6beta 1 and
      alphaVbeta 5 were stronger than other heterodimers in a referenced human ESC
      line. 

PMID- 23974175
TI  - Interactions between developing nerves and salivary glands.
AB  - Our aim is to provide a summary of the field of salivary gland development and
      regeneration from the perspective of what is known about the function of nerves
      during these processes. The primary function of adult salivary glands is to
      produce and secrete saliva. Neuronal control of adult salivary gland function has
      been a focus of research ever since Pavlov's seminal experiments on salivation in
      dogs. Less is known about salivary gland innervation during development and how
      the developing nerves influence gland organogenesis and regeneration. Here, we
      will review what is known about the communication between the autonomic nervous
      system and the epithelium of the salivary glands during organogenesis. An
      important emerging theme is the instructive role of the nervous system on the
      epithelial stem/progenitor cells during development as well as regeneration after
      damage. We will provide a brief overview of the neuroanatomy of the salivary
      glands and discuss recent literature that begins to integrate neurobiology with
      epithelial organogenesis, which may provide paradigms for exploring these
      interactions in other organ systems. 

PMID- 23974174
TI  - Urinary bladder matrix promotes site appropriate tissue formation following right
      ventricle outflow tract repair.
AB  - The current prevalence and severity of heart defects requiring functional
      replacement of cardiac tissue pose a serious clinical challenge. Biologic
      scaffolds are an attractive tissue engineering approach to cardiac repair because
      they avoid sensitization associated with homograft materials and theoretically
      possess the potential for growth in similar patterns as surrounding native
      tissue. Both urinary bladder matrix (UBM) and cardiac ECM (C-ECM) have been
      previously investigated as scaffolds for cardiac repair with modest success, but
      have not been compared directly. In other tissue locations, bone marrow derived
      cells have been shown to play a role in the remodeling process, but this has not
      been investigated for UBM in the cardiac location, and has never been studied for
      C-ECM. The objectives of the present study were to compare the effectiveness of
      an organ-specific C-ECM patch with a commonly used ECM scaffold for myocardial
      tissue repair of the right ventricle outflow tract (RVOT), and to examine the
      role of bone marrow derived cells in the remodeling response. A chimeric rat
      model in which all bone marrow cells express green fluorescent protein (GFP) was
      generated and used to show the ability of ECM scaffolds derived from the heart
      and bladder to support cardiac function and cellular growth in the RVOT. The
      results from this study suggest that urinary bladder matrix may provide a more
      appropriate substrate for myocardial repair than cardiac derived matrices, as
      shown by differences in the remodeling responses following implantation, as well
      as the presence of site appropriate cells and the formation of immature,
      myocardial tissue. 

PMID- 23974176
TI  - Mechanisms of respiratory innervation during embryonic development.
AB  - During embryogenesis, the development of the respiratory tract is closely
      associated with the formation of an extensive neuronal network. While the topic
      of respiratory innervation is not new, and similar articles were published
      previously, recent studies using animal models and genetic tools are breathing
      new life into the field. In this review, we focus on signaling mechanisms that
      underlie innervation of the embryonic respiratory tract. 

PMID- 23974178
TI  - Genome architecture is a selectable trait that can be maintained by antagonistic
      pleiotropy.
AB  - Chromosomal rearrangements are mutations contributing to both within and between
      species variation; however their contribution to fitness is yet to be measured.
      Here we show that chromosomal rearrangements are pervasive in natural isolates of
      Schizosaccharomyces pombe and contribute to reproductive isolation. To determine
      the fitness effects of chromosome structure, we constructed two inversions and
      eight translocations without changing the coding sequence. We show that
      chromosomal rearrangements contribute to both reproductive success in meiosis and
      growth rate in mitosis with a strong genotype by environment interaction. These
      changes are accompanied by alterations in gene expression. Strikingly, we find
      several examples leading to antagonistic pleiotropy. Even though chromosomal
      rearrangements may have a deleterious effect during sexual reproduction, some
      compensate with a strong growth advantage in mitosis. Our results constitute the
      first quantification of fitness effects caused by de novo mutations that result
      in chromosomal rearrangement variation and suggest a mechanism for their
      maintenance in natural populations. 

PMID- 23974177
TI  - Small RNAs tackle large viruses: RNA interference-based antiviral defense against
      DNA viruses in insects.
AB  - The antiviral RNA interference (RNAi) pathway processes viral double-stranded RNA
      (dsRNA) into viral small interfering RNAs (vsiRNA) that guide the recognition and
      cleavage of complementary viral target RNAs. In RNA virus infections, viral
      replication intermediates, dsRNA genomes or viral structured RNAs have been
      implicated as Dicer-2 substrates. In a recent publication, we demonstrated that a
      double-stranded DNA virus, Invertebrate iridescent virus 6, is a target of the
      Drosophila RNAi machinery, and we proposed that overlapping converging
      transcripts base pair to form the dsRNA substrates for vsiRNA biogenesis. Here,
      we discuss the role of RNAi in antiviral defense to DNA viruses in Drosophila and
      other invertebrate model systems. 

PMID- 23974179
TI  - Summaries for patients. Primary care interventions to prevent tobacco use in
      children and adolescents: U.S. Preventive Services Task Force recommendation
      statement.

PMID- 23974180
TI  - Hospice from a Compounding Pharmacist's Perspective.
AB  - This article is written from the perspective of a compounding pharmacist. Its
      primary purpose is to confirm the importance of including a compounding
      pharmacist in the hospice care team, and it presents a short summary of how
      hospice began, its primary focus, the makeup of a hospice team, and suggested
      compounded treatments for common problems in hospice patients. Since nausea is a
      primary problem for patients in hospice, included with the article are lists of
      the causes for nausea and of drugs used to treat nausea and their actions. Relief
      of nausea is a positive example of how a compounding pharmacist can play a vital
      and compassionate role in improving the quality of life during the dying process.

PMID- 23974181
TI  - ABHR Gel in the Treatment of Nausea and Vomiting in the Hospice Patient.
AB  - Hospice patients at the end stages of life often suffer nausea and vomiting,
      distressing symptoms that are either side effects of medications or direct
      effects of the underlying disease state. Such symptoms can greatly diminish the
      hospice patient's quality of life. Effective pharmacotherapy is available, but in
      many cases traditional dosage forms are incompatible with the patient's physical
      condition, cause discomfort, or are difficult for family members to administer.
      In such cases, a compounded preparation containing lorazepam, diphenhydramine,
      haloperidol, and metoclopramide-commonly referred to as ABHR gel-has proven
      highly effective. A number of case reports are presented to illustrate the
      effectiveness of ABHR gel in relieving the symptoms of nausea and vomiting in
      hopice patients. Also discussed are the causes of vomiting and the mechanisms of
      each of the medications contained in the ABHR gel. 

PMID- 23974182
TI  - The story of hospice.

PMID- 23974183
TI  - The dying process.
AB  - Caring for the dying and their loved ones is challenging; most patients and their
      families find themselves overwhelmed by the many physical and emotional stages of
      dying. The caregiver team involved in a dying patient's care is extensive, and
      included in this team is the compounding pharmacist. This article provides
      definitions and features of the dying process. It discusses the role of hospice
      care and palliative care; the importance of including a compounding pharmacist in
      the patient's care; physical changes experienced by the dying patient; and some
      of the myths involved in the dying process. 

PMID- 23974184
TI  - Probiotic therapy,part 1: beneficial bacteria improve health, save lives.

PMID- 23974185
TI  - Is your cleanroom clean? An in-depth look at cleaning and disinfecting agents,
      procedures, and requirements for the compounding pharmacist.
AB  - A system for fulfilling the objectives of cleaning/disinfecting and controlling
      the environment of a cleanroom must be established. Some of the organizations
      that have established standards in designing a system include the International
      Organization for Standardization, the United States Pharmacopeia, and the US
      Environmental Protection Agency. To design a system specifically for your
      pharmacy, you must conduct the initial assessment of your pharmacy's specific
      environment, the categories of surface chemical treatments, steps on selecting
      the proper chemical treatments, cleaning/disinfecting and control techniques; and
      verification testing. 

PMID- 23974186
TI  - Basics for compounding for dentistry, part 1: effective approaches and
      formulations.
AB  - Dental practice has expanded beyond its traditions of caring for teeth and gums.
      Today's dentists are trained to recognize and treat many different conditions of
      the head and neck. The increasing demand for individualized treatment continues
      to create expanding opportunities for pharmacists in the area of dental
      compounding. The majority of compounded formulations used by dentists are for
      direct application to the oral cavity, usually in the forms of mouthwashes, or
      oral pastes or powders. Endodontic procedures require a variety of solutions that
      can be compounded for professional office use only. Examples of all of these
      types of compounded preparations are provided. 

PMID- 23974187
TI  - Controlled environment testing association applications guide for the use of
      barrier isolators in comounding sterile preparations in healthcare facilities,
      part 1.
AB  - The Controlled Environment Testing Association guide focuses on isolator
      applications that are appropriate for use in facilities that compound sterile
      preparations. Owing to the fact that there are no uniform industry standards for
      the manufacture of barrier isolators. The purpose of this guide is to increase
      pharmacists' awareness of the need to establish procedures addressing issues
      unique to isolators. This article (Part 1 ) provides critical information on
      major design features of isolators, including airflow, flow control, and dilution
      control. Part 2 provides critical information on pressurization, clean zone
      classification, decontamination/disinfection, gloves/sleeves, closed system
      versus open system, pass-through considerations, and ergonomic considerations. In
      the future, Controlled Environment Testing Association will publish a guide-not a
      testing "standard"-for industry procedures for testing and commissioning
      isolators, as no published industry procedures are available at this time. 

PMID- 23974188
TI  - Initial Selection of Antiemetics in End-of-Life Care: A Retrospecitve Analysis.
AB  - The purpose of this study was to compare the relative severity of nausea and
      vomiting scores before and after initiation of treatnment regimens in end-of-life
      cancer patients, and secondarily to evaluate the efficacy of a combination
      antiemetic preparation (ABHR; lorazepam [Ativan], diphenhydramine [Benadryl],
      haloperidol [Haldol], and metoclopramide [Reglan] in this patient population. A
      retrospective analysis of antiemetic use was performed through a systematic chart
      review of patients with an end-of-life diagnosis of lung, pancreatic, or
      colorectal cancer whose medications were provided through Hospice Pharmacia.
      Information collected included patient age and sex; terminal diagnosis; pre- and
      post-antiemetic nausea and vomiting scores; and initial antiemetic choice. A
      total of 584 patient records were examined, and the most widely used antiemetics
      used were prochlorperazine, metoclopramide, and ABHR. The most prevalent
      diagnosis was lung cancer. All of the agents and preparations were determined to
      be effective as intial therapy for the management of nausea and vomiting in the
      end-of-life cancer patient; therefore use of these agents as first-line therapy
      options in this population appears to be justified. ABHR appears to be at least
      as efficacious as other first-line monotherapy options investigated. Despite a
      lack of information on the absolute bioavailability of alternative ABHR dosage
      forms such as suppositories and topical gels, these also appear to be efficacious
      and therefore are viable options in the treatment of nausea and vomiting in end
      of-life cancer patients. 

PMID- 23974189
TI  - Chemical stability of diclofenac sodium injection.
AB  - The stability of diclofenac sodium injection was studied by means of a stability
      indicating high-performance liquid chromatography assay method that was developed
      in our laboratory. There was a direct relationship between the peak heights and
      the concentrations. The percent relative standard deviation based on five
      injections was 0.9. The products of decomposition and the excipients present in
      the dosage form did not interfere with the developed assay method. The injection
      was stable for at least 23 days when stored in clear glass vials at room
      temperature. Contrary to the recommendation in the literature, the injection may
      not be stored at the refrigerated temperature. The physcial appearacne and the pH
      value of the injection did not change during the study period. 

PMID- 23974191
TI  - PostScription: Treatment of Chronic Pain with Methadone or Levorphanol.

PMID- 23974190
TI  - Extended stability of oxytocin in common infusion solutions.
AB  - The objective of this study was to evaluate the physical and chemical stability
      of oxytocin 0.08 U/mL admixed in 5% dextrose injection, 0.9% sodium chloride
      injection, and lactated Ringer's injection bags. Triplicate test samples of
      oxytocin 0.08 U/mL in each infusion solution were prepared by adding the required
      amount of oxytocin injection to bags of the three infusion solutions. The samples
      were stored protected from light and evaluated at appropriate intervals for up to
      90 days at room temperature (near 23 deg C). Physical stability was assessed by
      using an evaluation procedure that included both turbidimetric measurement and
      visual inspection. Chemical stability was assessed by using a stability
      indicating high-performance liquid chromatographic analytical technique and was
      based on the determination of drug concentrations initally and at appropriate
      intervals over the study period. The oxytocin admixtures in 5% dextrose and 0.9%
      sodium chloride were clear and colorless when viewed in normal fluorescent room
      light and when viewed with a Tyndall beam initially and throughout 90 days.
      Measured turbidity was low initially and exhibited little change throughout the
      study. High-performance liquid chromatographic analysis revealed that little or
      no decomposition occurred in the samples. Oxytocin in the infusion solutions
      remained stable at room temperature for 90 days. The lactated Ringer's injection
      samples remained clear and colorless for up to 28 days. However, after that time
      a small amount of white fluffy microprecipitate developed in two of the three
      samples by the 35-day observation point. High-performance liquid chromatographic
      analysis revealed that oxytocin remained stable in lactated Ringer's injection
      for 28 days at room temperature; substantial losses of oxytocin occurred in all
      three samples after that time, with about 10% loss at 35 days and up to 21% loss
      at 60 days. Oxytocin 0.08 U/mL in 5% dextrose injection or 0.9% sodium chloride
      injection is physically and chemically stable for at least 90 days at room
      temperature. However, oxytocin in lactated Ringer's injection should be
      restricted to a use period no greater than 28 days at room temperature to avoid
      microprecipitate formation and drug loss. 

PMID- 23974193
TI  - Pomalidomide.
AB  - This spotlight review focuses on the second-generation immunomodulatory drug
      pomalidomide, which was recently approved by the US Food and Drug Administration.
      This drug was approved for patients with multiple myeloma who have received at
      least 2 prior therapies, including lenalidomide and bortezomib, and have
      demonstrated disease progression on or within 60 days of completion of the last
      therapy. This review focuses on the clinical trial data that led to approval and
      provides advice for treating physicians who are now prescribing this drug for
      patients. 

PMID- 23974192
TI  - Independent prognostic value of BCR-ABL1-like signature and IKZF1 deletion, but
      not high CRLF2 expression, in children with B-cell precursor ALL.
AB  - Most relapses in childhood B-cell precursor acute lymphoblastic leukemia (BCP
      ALL) are not predicted using current prognostic features. Here, we determined the
      co-occurrence and independent prognostic relevance of 3 recently identified
      prognostic features: BCR-ABL1-like gene signature, deletions in IKZF1, and high
      CRLF2 messenger RNA expression (CRLF2-high). These features were determined in 4
      trials representing 1128 children with ALL: DCOG ALL-8, ALL9, ALL10, and
      Cooperative ALL (COALL)-97/03. BCR-ABL1-like, IKZF1-deleted, and CRLF2-high cases
      constitute 33.7% of BCR-ABL1-negative, MLL wild-type BCP-ALL cases, of which BCR
      ABL1-like and IKZF1 deletion (co)occurred most frequently. Higher cumulative
      incidence of relapse was found for BCR-ABL1-like and IKZF1-deleted, but not CRLF2
      high, cases relative to remaining BCP-ALL cases, reflecting the observations in
      each of the cohorts analyzed separately. No relapses occurred among cases with
      CRLF2-high as single feature, whereas 62.9% of all relapses in BCR-ABL1-negative,
      MLL wild-type BCP-ALL occurred in cases with BCR-ABL1-like signature and/or IKZF1
      deletion. Both the BCR-ABL1-like signature and IKZF1 deletions were prognostic
      features independent of conventional prognostic markers in a multivariate model,
      and both remained prognostic among cases with intermediate minimal residual
      disease. The BCR-ABL1-like signature and an IKZF1 deletion, but not CRLF2-high,
      are prognostic factors and are clinically of importance to identify high-risk
      patients who require more intensive and/or alternative therapies. 

PMID- 23974194
TI  - The impact of response on bone-directed therapy in patients with multiple
      myeloma.
AB  - Significant benefits for zoledronic acid (ZOL) over clodronate acid (CLO) were
      seen in the Medical Research Council Myeloma IX randomized trial. ZOL
      significantly reduced skeletal-related events (SREs), and improved progression
      free survival and overall survival (OS), making it the bisphosphonate of choice
      for newly diagnosed myeloma patients. In this analysis of Myeloma IX data, we
      have investigated the impact of response on bone disease in 1111 transplant
      eligible patients. At posttransplant day 100, complete response (CR) was seen in
      48% of patients, very good partial response (VGPR) in 20%, and partial response
      (PR) in 23%. For patients in VGPR or less, ZOL was superior to CLO in reducing
      SREs (P = .048), whereas for patients in CR, both agents were equivalent (P =
      .83). For OS, ZOL was associated with a significant benefit in patients in PR (P
      = .0091). No difference in OS was seen with patients in CR (P = .91) or VGPR (P =
      .74). These findings indicate that response category posttransplant may influence
      the impact of bisphosphonate therapy.

PMID- 23974195
TI  - Mixed hematopoietic or T-cell chimerism above a minimal threshold restores
      perforin-dependent immune regulation in perforin-deficient mice.
AB  - Defects in perforin and related genes lead to a loss of normal immune regulation
      and underlie hemophagocytic lymphohistiocytosis (HLH), which requires
      hematopoietic cell transplantation for long-term cure. However, transplantation
      may be complicated by the development of mixed chimerism and uncertainty
      regarding the risk of HLH recurrence. To help clarify this risk and investigate
      how perforin influences immune activation, we studied perforin-mediated immune
      regulation in the context of mixed chimerism using a murine model of HLH. We
      found that there is a distinct threshold of ~10% to 20% perforin expression with
      either mixed hematopoietic or CD8(+) T cell chimerism, above which immune
      regulation was reestablished. These findings demonstrate that perforin-mediated
      immunoregulation functions in trans and are consistent with a feedback model in
      which cytotoxic T cells control immune activation by killing dendritic cells.
      These findings also suggest rational targets for maintenance of minimal
      posttransplant chimerism and for therapeutic strategies involving gene
      correction. 

PMID- 23974196
TI  - Innate immune control of EBV-infected B cells by invariant natural killer T
      cells.
AB  - Individuals with X-linked lymphoproliferative disease lack invariant natural
      killer T (iNKT) cells and are exquisitely susceptible to Epstein-Barr virus (EBV)
      infection. To determine whether iNKT cells recognize or regulate EBV, resting B
      cells were infected with EBV in the presence or absence of iNKT cells. The
      depletion of iNKT cells increased both viral titers and the frequency of EBV
      infected B cells. However, EBV-infected B cells rapidly lost expression of the
      iNKT cell receptor ligand CD1d, abrogating iNKT cell recognition. To determine
      whether induced CD1d expression could restore iNKT recognition in EBV-infected
      cells, lymphoblastoid cell lines (LCL) were treated with AM580, a synthetic
      retinoic acid receptor-alpha agonist that upregulates CD1d expression via the
      nuclear protein, lymphoid enhancer-binding factor 1 (LEF-1). AM580 significantly
      reduced LEF-1 association at the CD1d promoter region, induced CD1d expression on
      LCL, and restored iNKT recognition of LCL. CD1d-expressing LCL elicited
      interferon gamma secretion and cytotoxicity by iNKT cells even in the absence of
      exogenous antigen, suggesting an endogenous iNKT antigen is expressed during EBV
      infection. These data indicate that iNKT cells may be important for early, innate
      control of B cell infection by EBV and that downregulation of CD1d may allow EBV
      to circumvent iNKT cell-mediated immune recognition. 

PMID- 23974197
TI  - Local apoptosis mediates clearance of macrophages from resolving inflammation in
      mice.
AB  - Chronic inflammatory diseases such as atherosclerosis are characterized by an
      accumulation of macrophages. To design therapies that would reduce macrophage
      burden during disease, understanding the cellular and molecular mechanisms that
      regulate macrophage removal from sites of resolving inflammation is critical.
      Although past studies have considered the local death of macrophages or the
      possibility that they emigrate out of inflammatory foci, methods to quantify
      death or emigration have never been employed. Here, we applied quantitative
      competition approaches and other methods to study resolution of thioglycollate
      induced peritonitis, the model in which earlier work indicated that emigration to
      lymph nodes accounted for macrophage removal. We show that migration to lymph
      nodes occurred in a CC chemokine receptor 7-independent manner but, overall, had
      a quantitatively minor role in the removal of macrophages. Blocking migration did
      not significantly delay resolution. However, when macrophages resistant to death
      were competed against control macrophages, contraction of the macrophage pool was
      delayed in the apoptosis-resistant cells. These data refute the concept that
      macrophages are dominantly cleared through emigration and indicate that local
      death controls macrophage removal. This finding alters the emphasis on which
      cellular processes merit targeting in chronic diseases associated with
      accumulation of macrophages. 

PMID- 23974199
TI  - Genome-wide analysis of transcriptional regulators in human HSPCs reveals a
      densely interconnected network of coding and noncoding genes.
AB  - Genome-wide combinatorial binding patterns for key transcription factors (TFs)
      have not been reported for primary human hematopoietic stem and progenitor cells
      (HSPCs), and have constrained analysis of the global architecture of molecular
      circuits controlling these cells. Here we provide high-resolution genome-wide
      binding maps for a heptad of key TFs (FLI1, ERG, GATA2, RUNX1, SCL, LYL1, and
      LMO2) in human CD34(+) HSPCs, together with quantitative RNA and microRNA
      expression profiles. We catalog binding of TFs at coding genes and microRNA
      promoters, and report that combinatorial binding of all 7 TFs is favored and
      associated with differential expression of genes and microRNA in HSPCs. We also
      uncover a previously unrecognized association between FLI1 and RUNX1 pairing in
      HSPCs, we establish a correlation between the density of histone modifications
      that mark active enhancers and the number of overlapping TFs at a peak, we
      demonstrate bivalent histone marks at promoters of heptad target genes in CD34(+)
      cells that are poised for later expression, and we identify complex relationships
      between specific microRNAs and coding genes regulated by the heptad. Taken
      together, these data reveal the power of integrating multifactor sequencing of
      chromatin immunoprecipitates with coding and noncoding gene expression to
      identify regulatory circuits controlling cell identity. 

PMID- 23974198
TI  - The common hereditary elliptocytosis-associated alpha-spectrin L260P mutation
      perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer
      conformation.
AB  - Hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP) are common
      disorders of erythrocyte shape primarily because of mutations in spectrin. The
      most common HE/HPP mutations are located distant from the critical alphabeta
      spectrin tetramerization site, yet still interfere with formation of spectrin
      tetramers and destabilize the membrane by unknown mechanisms. To address this
      question, we studied the common HE-associated mutation, alphaL260P, in the
      context of a fully functional mini-spectrin. The mutation exhibited wild-type
      tetramer binding in univalent binding assays, but reduced binding affinity in
      bivalent-binding assays. Biophysical analyses demonstrated the mutation
      containing domain was only modestly structurally destabilized and helical content
      was not significantly changed. Gel filtration analysis of the alphaL260P mini
      spectrin indicated more compact structures for dimers and tetramers compared with
      wild-type. Chemical crosslinking showed structural changes in the mutant mini
      spectrin dimer were primarily restricted to the vicinity of the alphaL260P
      mutation and indicated large conformational rearrangements of this region. These
      data indicate the mutation increased the stability of the closed dimer state,
      thereby reducing tetramer assembly and resulting in membrane destabilization.
      These results reveal a novel mechanism of erythrocyte membrane destabilization
      that could contribute to development of therapeutic interventions for mutations
      in membrane proteins containing spectrin-type domains associated with inherited
      disease. 

PMID- 23974200
TI  - Transcription factor C/EBPalpha-induced microRNA-30c inactivates Notch1 during
      granulopoiesis and is downregulated in acute myeloid leukemia.
AB  - The transcription factor CCAAT enhancer binding protein alpha (C/EBPalpha) is a
      master regulator in granulopoiesis and is frequently disrupted in acute myeloid
      leukemia (AML). We have previously shown that C/EBPalpha exerts its effects by
      regulating microRNAs (miRs) such as miR-223 and miR-34a. Here, we confirm miR-30c
      as a novel important target of C/EBPalpha during granulopoiesis. Thus, wild-type
      C/EBPalpha-p42 directly upregulates miR-30c expression, whereas C/EBPalpha-p30,
      found in AML, does not. miR-30c is downregulated in AML, especially in normal
      karyotype AML patients with CEBPA mutations. An induced C/EBPalpha knockout in
      mice leads to a significant downregulation of miR-30c expression in bone marrow
      cells. We identified NOTCH1 as a direct target of miR-30c. Finally, a block of
      miR-30c prevents C/EBPalpha-induced downregulation of Notch1 protein and leads to
      a reduced CD11b expression in myeloid differentiation. Our study presents the
      first evidence that C/EBPalpha, miR-30c, and Notch1 together play a critical role
      in granulocytic differentiation and AML, and particularly in AML with CEBPA
      mutations. These data reveal the importance of deregulated miRNA expression in
      leukemia and may provide novel biomarkers and therapeutic targets in AML. 

PMID- 23974201
TI  - Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and
      biological entity: a collaborative study by the International-Berlin-Frankfurt
      Munster AML-study group.
AB  - In pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong
      indicators of prognosis. Some recurrent cytogenetic abnormalities, such as
      t(8;16)(p11;p13), are so rare that collaborative studies are required to define
      their prognostic impact. We collected the clinical characteristics, morphology,
      and immunophenotypes of 62 pediatric AML patients with t(8;16)(p11;p13) from 18
      countries participating in the International Berlin-Frankfurt-Munster (I-BFM) AML
      study group. We used the AML-BFM cohort diagnosed from 1995-2005 (n = 543) as a
      reference cohort. Median age of the pediatric t(8;16)(p11;p13) AML patients was
      significantly lower (1.2 years). The majority (97%) had M4-M5 French-American
      British type, significantly different from the reference cohort.
      Erythrophagocytosis (70%), leukemia cutis (58%), and disseminated intravascular
      coagulation (39%) occurred frequently. Strikingly, spontaneous remissions
      occurred in 7 neonates with t(8;16)(p11;p13), of whom 3 remain in continuous
      remission. The 5-year overall survival of patients diagnosed after 1993 was 59%,
      similar to the reference cohort (P = .14). Gene expression profiles of
      t(8;16)(p11;p13) pediatric AML cases clustered close to, but distinct from, MLL
      rearranged AML. Highly expressed genes included HOXA11, HOXA10, RET, PERP, and
      GGA2. In conclusion, pediatric t(8;16)(p11;p13) AML is a rare entity defined by a
      unique gene expression signature and distinct clinical features in whom
      spontaneous remissions occur in a subset of neonatal cases. 

PMID- 23974202
TI  - Genome-scale expression and transcription factor binding profiles reveal
      therapeutic targets in transgenic ERG myeloid leukemia.
AB  - The ETS transcription factor ERG plays a central role in definitive
      hematopoiesis, and its overexpression in acute myeloid leukemia (AML) is
      associated with a stem cell signature and poor prognosis. Yet how ERG causes
      leukemia is unclear. Here we show that pan-hematopoietic ERG expression induces
      an early progenitor myeloid leukemia in transgenic mice. Integrated genome-scale
      analysis of gene expression and ERG binding profiles revealed that ERG activates
      a transcriptional program similar to human AML stem/progenitor cells and to human
      AML with high ERG expression. This transcriptional program was associated with
      activation of RAS that was required for leukemia cells growth in vitro and in
      vivo. We further show that ERG induces expression of the Pim1 kinase oncogene
      through a novel hematopoietic enhancer validated in transgenic mice and human
      CD34(+) normal and leukemic cells. Pim1 inhibition disrupts growth and induces
      apoptosis of ERG-expressing leukemic cells. The importance of the ERG/PIM1 axis
      is further underscored by the poorer prognosis of AML highly expressing ERG and
      PIM1. Thus, integrative genomic analysis demonstrates that ERG causes myeloid
      progenitor leukemia characterized by an induction of leukemia stem cell
      transcriptional programs. Pim1 and the RAS pathway are potential therapeutic
      targets of these high-risk leukemias. 

PMID- 23974205
TI  - Mechanism of wavelength conversion in polystyrene doped with benzoxanthene:
      emergence of a complex.
AB  - Fluorescent guest molecules doped in polymers have been used to convert
      ultraviolet light into visible light for applications ranging from optical fibres
      to filters for the cultivation of plants. The wavelength conversion process
      involves the absorption of light at short wavelengths followed by fluorescence
      emission at a longer wavelength. However, a precise understanding of the light
      conversion remains unclear. Here we show light responses for a purified
      polystyrene base substrates doped with fluorescent benzoxanthene in
      concentrations varied over four orders of magnitude. The shape of the excitation
      spectrum for fluorescence emission changes significantly with the concentration
      of the benzoxanthene, indicating formation of a base substrate/fluorescent
      molecule complex. Furthermore, the wavelength conversion light yield increases in
      three stages depending on the nature of the complex. These findings identify a
      mechanism that will have many applications in wavelength conversion materials. 

PMID- 23974203
TI  - Genome-wide DNA methylation analysis identifies hypomethylated genes regulated by
      FOXP3 in human regulatory T cells.
AB  - Regulatory T cells (Treg) prevent the emergence of autoimmune disease. Prototypic
      natural Treg (nTreg) can be reliably identified by demethylation at the Forkhead
      box P3 (FOXP3) locus. To explore the methylation landscape of nTreg, we analyzed
      genome-wide methylation in human naive nTreg (rTreg) and conventional naive
      CD4(+) T cells (Naive). We detected 2315 differentially methylated cytosine
      guanosine dinucleotides (CpGs) between these 2 cell types, many of which
      clustered into 127 regions of differential methylation (RDMs). Activation changed
      the methylation status of 466 CpGs and 18 RDMs in Naive but did not alter DNA
      methylation in rTreg. Gene-set testing of the 127 RDMs showed that promoter
      methylation and gene expression were reciprocally related. RDMs were enriched for
      putative FOXP3-binding motifs. Moreover, CpGs within known FOXP3-binding regions
      in the genome were hypomethylated. In support of the view that methylation limits
      access of FOXP3 to its DNA targets, we showed that increased expression of the
      immune suppressive receptor T-cell immunoglobulin and immunoreceptor tyrosine
      based inhibitory motif domain (TIGIT), which delineated Treg from activated
      effector T cells, was associated with hypomethylation and FOXP3 binding at the
      TIGIT locus. Differential methylation analysis provides insight into previously
      undefined human Treg signature genes and their mode of regulation. 

PMID- 23974204
TI  - Aurora and IKK kinases cooperatively interact to protect multiple myeloma cells
      from Apo2L/TRAIL.
AB  - Constitutive activation of the canonical and noncanonical nuclear factor-kappaB
      (NF-kappaB) pathways is frequent in multiple myeloma (MM) and can compromise
      sensitivity to TRAIL. In this study, we demonstrate that Aurora kinases
      physically and functionally interact with the key regulators of canonical and
      noncanonical NF-kappaB pathways IkappaB kinase beta (IKKbeta) and IKKalpha to
      activate NF-kappaB in MM, and the pharmacological blockade of Aurora kinase
      activity induces TRAIL sensitization in MM because it abrogates TRAIL-induced
      activation of NF-kappaB. We specifically found that TRAIL induces prosurvival
      signaling by increasing the phosphorylation state of both Aurora and IKK kinases
      and their physical interactions, and the blockade of Aurora kinase activity by
      pan-Aurora kinase inhibitors (pan-AKIs) disrupts TRAIL-induced survival signaling
      by effectively reducing Aurora-IKK kinase interactions and NF-kappaB activation.
      Pan-AKIs consistently blocked TRAIL induction of the antiapoptotic NF-kappaB
      target genes A1/Bfl-1 and/or Mcl-1, both important targets for TRAIL
      sensitization in MM cells. In summary, these results identify a novel interaction
      between Aurora and IKK kinases and show that these pathways can cooperate to
      promote TRAIL resistance. Finally, combining pan-AKIs with TRAIL in vivo showed
      dramatic efficacy in a multidrug-resistant human myeloma xenograft model. These
      findings suggest that combining Aurora kinase inhibitors with TRAIL may have
      therapeutic benefit in MM. 

PMID- 23974206
TI  - Worse pancreatic beta-cell function and better insulin sensitivity in older
      Chinese without diabetes.
AB  - BACKGROUND: Whether insulin secretion and insulin sensitivity in older Chinese
      differ from younger persons without diabetes has not been examined and is unknown
      to us. METHODS: Oral glucose tolerance test was performed in a total of 32,245
      Chinese without diabetes history. Insulin sensitivity was estimated by Matsuda's
      insulin sensitivity index (Matsuda ISI), and insulin secretion was measured by
      the insulinogenic index. The insulin secretion and sensitivity were compared
      among three age groups: 20-39 (the young), 40-59 (the middle), and greater than
      or equal to 60 years (the older). RESULTS: A higher proportion of postchallenge
      hyperglycemia (PH), both in prediabetes and in diabetes stage, was associated
      with older age. In the young, middle, and older age groups, the insulinogenic
      index median was 10.64, 8.40, and 6.67, respectively, in individuals with normal
      glucose tolerance (NGT); it was 8.56, 6.12, and 4.98 in individuals with
      prediabetes, respectively (p < .001 vs the young group). In these three age
      groups, the Matsuda insulin sensitivity index was 8.20, 8.39, and 8.84 in
      individuals with normal glucose tolerance, and it was 5.23, 5.94, and 6.33 in
      individuals with prediabetes, respectively (p < .05 vs the young group). These
      differences were independent of body mass index and waist circumference.
      CONCLUSIONS: Older Chinese without diabetes are characterized with worse insulin
      secretion and better insulin sensitivity. Insulin insufficiency and insulin
      resistance may contribute disproportionately to abnormal glucose tolerance in
      people of different age.

PMID- 23974207
TI  - Evidence for less marked potential signs of T-cell immunosenescence in
      centenarian offspring than in the general age-matched population.
AB  - People may reach the upper limits of the human life span at least partly because
      they have maintained more appropriate immune function, avoiding changes to
      immunity termed "immunosenescence." Exceptionally long-lived people may be
      enriched for genes that contribute to their longevity, some of which may bear on
      immune function. Centenarian offspring would be expected to inherit some of
      these, which might be reflected in their resistance to immunosenescence, and
      contribute to their potential longevity. We have tested this hypothesis by
      comparing centenarian offspring with age-matched controls. We report differences
      in the numbers and proportions of both CD4(+) and CD8(+) early- and late
      differentiated T cells, as well as potentially senescent CD8(+) T cells,
      suggesting that the adaptive T-cell arm of the immune system is more "youthful"
      in centenarian offspring than controls. This might reflect a superior ability to
      mount effective responses against newly encountered antigens and thus contribute
      to better protection against infection and to greater longevity. 

PMID- 23974208
TI  - Split photosystem protein, linear-mapping topology, and growth of structural
      complexity in the plastid genome of Chromera velia.
AB  - The canonical photosynthetic plastid genomes consist of a single circular-mapping
      chromosome that encodes a highly conserved protein core, involved in
      photosynthesis and ATP generation. Here, we demonstrate that the plastid genome
      of the photosynthetic relative of apicomplexans, Chromera velia, departs from
      this view in several unique ways. Core photosynthesis proteins PsaA and AtpB have
      been broken into two fragments, which we show are independently transcribed,
      oligoU-tailed, translated, and assembled into functional photosystem I and ATP
      synthase complexes. Genome-wide transcription profiles support expression of many
      other highly modified proteins, including several that contain extensions
      amounting to hundreds of amino acids in length. Canonical gene clusters and
      operons have been fragmented and reshuffled into novel putative transcriptional
      units. Massive genomic coverage by paired-end reads, coupled with pulsed-field
      gel electrophoresis and polymerase chain reaction, consistently indicate that the
      C. velia plastid genome is linear-mapping, a unique state among all plastids.
      Abundant intragenomic duplication probably mediated by recombination can explain
      protein splits, extensions, and genome linearization and is perhaps the key
      driving force behind the many features that defy the conventional ways of plastid
      genome architecture and function. 

PMID- 23974209
TI  - Prognosis of hospitalised older people with different levels of functioning: a
      prospective cohort study.
AB  - BACKGROUND: hospitalised older people are at risk for poor functioning after
      hospital discharge. We aimed to validate the predictive ability of the
      Identification Seniors At Risk-Hospitalized Patients (ISAR-HP) screening
      questionnaire to identify older patients at risk for functional dependence by
      comparing groups with different ISAR-HP scores on cognitive and physical
      functioning, mortality, health-related quality of life (HRQoL) and loneliness.
      DESIGN: a longitudinal prospective cohort study. SETTING: a 450-bed hospital in
      the Netherlands. SUBJECTS: four hundred and sixty patients 65 years or older
      admitted between June 2010 and October 2010. METHODS: participants were
      classified into five risk groups at hospital admission using the ISAR-HP. We
      interviewed patients at hospital admission and at 3 and 12 months after admission
      using validated questionnaires to score HRQoL, physical functioning, cognitive
      functioning and loneliness. Differences in survival were quantified by a
      concordance statistic (c). RESULTS: cognitive functioning, physical functioning,
      loneliness and HRQoL differed significantly between groups during the 1-year
      follow-up after hospital admission (all comparisons P < 0.05), with high-risk
      groups having lower scores than low-risk groups for functioning and loneliness,
      although not always for HRQoL. The lowest risk group (ISAR-HP = 0) scored
      consistently higher on functioning and HRQoL than all other groups. Mortality
      differed significantly between groups (P < 0.001, c = 0.67). CONCLUSIONS: the
      ISAR-HP can readily distinguish well-functioning older patients from patients
      with low functioning and low HRQoL after hospital admission. The ISAR-HP may
      hence assist in selecting patients who may benefit from individually tailored
      reactivation treatment that is provided next to treatment of their medical
      condition.

PMID- 23974210
TI  - Effects of time-of-day and partial sleep deprivation on short-term maximal
      performances of judo competitors.
AB  - This study assessed the effects of partial sleep deprivation on short-term
      maximal performances of judokas in the morning and afternoon of the following
      day. In a randomized design, 12 judokas completed the maximal voluntary
      contraction, the handgrip, and the Wingate tests before and after a judo combat.
      Measurements were performed at 09:00 and 16:00 hours after a reference-normal
      sleep night and 2 conditions of 4-hour partial sleep deprivation timed at the
      beginning (SDB) or at the end of the night (SDE). The results showed that muscle
      power and strength were significantly higher at 16:00 than 09:00 hours (p <
      0.05). These diurnal variations disappeared after SDB and SDE and after the
      combat. In addition, SDE resulted in significant decreases of short-term maximal
      performance in the afternoon (p < 0.01). In conclusion, SDE decreased muscle
      strength and power at 16:00 hours and, therefore, might have blunted the diurnal
      variations of short-term maximal exercise. Thus, early rising is more detrimental
      than late bedtime to muscle strength and power for judo athletes when
      competitions are scheduled in the afternoon hours.

PMID- 23974211
TI  - SpoIIIE protein achieves directional DNA translocation through allosteric
      regulation of ATPase activity by an accessory domain.
AB  - Bacterial chromosome segregation utilizes highly conserved directional
      translocases of the SpoIIIE/FtsK family. These proteins employ an accessory DNA
      binding domain (gamma) to dictate directionality of DNA transport. It remains
      unclear how the interaction of gamma with specific recognition sequences
      coordinates directional DNA translocation. We demonstrate that the gamma domain
      of SpoIIIE inhibits ATPase activity of the motor domain in the absence of DNA but
      stimulates ATPase activity through sequence-specific DNA recognition.
      Furthermore, we observe that communication between gamma subunits is necessary
      for both regulatory roles. Consistent with these findings, the gamma domain is
      necessary for robust DNA transport along the length of the chromosome in vivo.
      Together, our data reveal that directional activation involves allosteric
      regulation of ATP turnover through coordinated action of gamma domains. Thus, we
      propose a coordinated stimulation model in which gamma-gamma communication is
      required to translate DNA sequence information from each gamma to its respective
      motor domain. 

PMID- 23974213
TI  - Psoriatic keratinocytes prime neutrophils for an overproduction of superoxide
      anions.
AB  - Psoriatic plaques result from an abnormal proliferation of keratinocytes
      associated with the local presence of T lymphocytes and neutrophils. The exact
      role of neutrophils in psoriatic lesions remains unclear. The present
      investigation was aimed at deciphering the capacity of psoriatic keratinocytes to
      alter in vitro functions of neutrophils. Blood neutrophils from healthy donors
      were incubated with psoriatic (PK) or healthy keratinocytes (HK) with and without
      IL-2-activated healthy T lymphocytes. The study was focussed on neutrophil
      capacity of adherence, viability and superoxide anion production. PK or HK with
      or without T lymphocytes similarly augmented neutrophil viability after 48 h of
      co-incubation. PK or HK did not directly activate the superoxide production by
      neutrophils. However, they both primed neutrophils for an increased fMLF-induced
      production of superoxide, an effect enhanced by the presence of T lymphocytes. PK
      were 1.5-fold more efficient than HK to augment this superoxide production. PK
      cultured with T lymphocytes induced the adhesion of neutrophils 4.7 times more
      efficiently than HK. The adherence of neutrophils was mediated through ICAM-1,
      LFA-1 and Mac-1, independently of bioactive lipids. The effects of PK and HK on
      neutrophil viability and priming were independent of direct cellular contact. In
      conclusion, keratinocytes can impact neutrophils by increasing their lifespan,
      and by priming them to overproduce superoxide. PK are more efficient than HK in
      priming neutrophils, an effect enhanced by T lymphocytes. These results indicate
      that neutrophils could contribute to psoriasis pathogenesis partly through their
      pathological interactions with PK. 

PMID- 23974212
TI  - RecA protein recruits structural maintenance of chromosomes (SMC)-like RecN
      protein to DNA double-strand breaks.
AB  - Escherichia coli RecN is an SMC (structural maintenance of chromosomes) family
      protein that is required for DNA double-strand break (DSB) repair. Previous
      studies show that GFP-RecN forms nucleoid-associated foci in response to DNA
      damage, but the mechanism by which RecN is recruited to the nucleoid is unknown.
      Here, we show that the assembly of GFP-RecN foci on the nucleoid in response to
      DNA damage involves a functional interaction between RecN and RecA. A novel RecA
      allele identified in this work, recA(Q300R), is proficient in SOS induction and
      repair of UV-induced DNA damage, but is deficient in repair of mitomycin C (MMC)
      induced DNA damage. Cells carrying recA(Q300R) fail to recruit RecN to DSBs and
      accumulate fragmented chromosomes after exposure to MMC. The ATPase-deficient
      RecN(K35A) binds and forms foci at MMC-induced DSBs, but is not released from the
      MMC-induced DNA lesions, resulting in a defect in homologous recombination
      dependent DSB repair. These data suggest that RecN plays a crucial role in
      homologous recombination-dependent DSB repair and that it is required upstream of
      RecA-mediated strand exchange. 

PMID- 23974214
TI  - Anaerobic digestion of municipal solid waste composed of food waste, wastepaper,
      and plastic in a single-stage system: performance and microbial community
      structure characterization.
AB  - The performance of municipal organic solid waste anaerobic digestion was
      investigated using a single-stage bioreactor, and the microbial community
      structures were characterized during the digestion. The results showed that the
      biogas and methane production rates were 592.4 and 370.1L/kg with volatile solid
      added at the ratio of 2:1:1 for food waste, wastepaper, and plastic based on dry
      weight. The methane volume concentration fluctuated between 44.3% and 75.4% at
      steady stage. Acetic acid, propionic acid, and butyric acid were the major
      volatile fatty acids produced during the digestion process. The anaerobic process
      was not inhibited by the accumulation of ammonia and free ammonia. The bacterial
      community was found to consist of at least 21 bands of bacteria and 12 bands of
      archaea at the steady state. All of the results indicated that the mixture of
      food waste, wastepaper, and plastic could be efficiently co-digested using the
      anaerobic digestion system. 

PMID- 23974215
TI  - Vimentin is a target of PKCbeta phosphorylation in MCP-1-activated primary human
      monocytes.
AB  - OBJECTIVE AND DESIGN: We designed a study to detect downstream phosphorylation
      targets of PKCbeta in MCP-1-induced human monocytes. METHODS: Two-dimensional gel
      electrophoresis was performed for monocytes treated with MCP-1 in the presence or
      absence of PKCbeta antisense oligodeoxyribonucleotides (AS-ODN) or a PKCbeta
      inhibitor peptide, followed by phospho- and total protein staining. Proteins that
      stained less intensely with the phospho-stain, when normalized to the total
      protein stain, in the presence of PKCbeta AS-ODN or the PKCbeta inhibitor
      peptide, were sequenced. RESULTS: Of the proteins identified, vimentin was
      consistently identified using both experimental approaches. Upon (32)P-labeling
      and vimentin immunoprecipitation, increased phosphorylation of vimentin was
      observed in MCP-1 treated monocytes as compared to the untreated monocytes. Both
      PKCbeta AS-ODN and the PKCbeta inhibitor reduced MCP-1-induced vimentin
      phosphorylation. The IP of monocytes with anti-vimentin antibody and
      immunoblotting with a PKCbeta antibody revealed that increased PKCbeta becomes
      associated with vimentin upon MCP-1 activation. Upon MCP-1 treatment, monocytes
      were shown to secrete vimentin and secretion depended on PKCbeta expression and
      activity. CONCLUSIONS: We conclude that vimentin, a major intermediate filament
      protein, is a phosphorylation target of PKCbeta in MCP-1-treated monocytes and
      that PKCbeta phosphorylation is essential for vimentin secretion. Our recently
      published studies have implicated vimentin as a potent stimulator of the innate
      immune receptor Dectin-1 as reported by Thiagarajan et al. (Cardiovasc Res 99:494
      504, 2013). Taken together our findings suggest that inhibition of PKCbeta
      regulates vimentin secretion and, thereby, its interaction with Dectin-1 and
      downstream stimulation of superoxide anion production. Thus, PKCbeta
      phosphorylation of vimentin likely plays an important role in propagating
      inflammatory responses.

PMID- 23974216
TI  - Hypoxia-based strategies for angiogenic induction: the dawn of a new era for
      ischemia therapy and tissue regeneration.
AB  - Therapeutic angiogenesis promises to aid the healing and regeneration of tissues
      suffering from a compromised vascular supply. Ischaemia therapy has so far
      primarily focused on delivering isolated angiogenic growth factors. The limited
      success of these strategies in clinical trials, however, is increasingly forcing
      researchers to recognize the difficulties associated with trying to mimic the
      angiogenic process, due to its natural complexity. Instead, a new school of
      thought is gradually emerging, focusing on how to induce angiogenesis at its
      onset, by utilizing hypoxia, the primary angiogenic stimulus in physiological, as
      well pathological states. This shift in therapeutic approach is underlined by the
      realization of the importance of depressed HIF-1 alpha-mediated gene programming
      in non-healing ischemic tissues, which could explain their apparent habituation
      to chronic hypoxic stress and the limited capacity to generate adaptive
      angiogenesis. Hypoxia-based strategies, then effectively aim to override the
      habituated angiogenic cellular response, re-start the regenerative process and
      drive it to completion. Here we make a distinction between those strategies that
      utilize hypoxia in vitro as a preconditioning tool to optimize the angiogenic
      potential of tissue/cells before transplantation, vs. strategies that aim to
      induce hypoxia-induced signaling in vivo, directly, through pharmacological means
      or gene transfer. We then discuss possible future directions for the field, as it
      moves into the phase of clinical trials. 

PMID- 23974217
TI  - Portocaval shunt for hepatocyte package: challenging application of small
      intestinal graft in animal models.
AB  - In developing therapeutic alternatives to liver transplantation, we have used the
      strategy of applying a small intestinal segment as a scaffold for hepatocyte
      transplantation and also as a portocaval shunt (PCS) system to address both liver
      dysfunction and portal hypertension. The aim of this study was to investigate the
      feasibility of such an intestinal segment in animal models. Hepatocytes isolated
      from luciferase-transgenic Lewis rats were transplanted into jejunal segments of
      wild-type Lewis rats with mucosa removal without PCS application. Luciferase
      derived luminescence from transplanted hepatocytes was stably detected for 30
      days. Then, we performed autologous hepatocyte transplantation into the
      submucosal layer of an isolated and vascularized small intestinal segment in
      pigs. Transplanted hepatocytes were isolated from the resected left-lateral lobe
      of the liver. On day 7, hepatocyte clusters and bile duct-like structures were
      observed histologically. To create an intestinal PCS system in pigs, an auto
      graft of the segmental ileum and interposing vessel graft were anastomosed to the
      portal vein trunk and inferior vena cava. However, thrombi were observed in
      vessels of the intestinal PCSs. We measured the correlation between infusion
      pressure and flow volume in whole intestines ex vivo in both species and found
      that the high pressure corresponding to portal hypertension was still
      insufficient to maintain the patency of the intestinal grafts. In conclusion, we
      demonstrated the feasibility of the small intestine as a scaffold for hepatocyte
      transplantation in rat and pig models, but PCS using an intestinal graft failed
      to maintain patency in a pig model. 

PMID- 23974219
TI  - Single walled carbon nanotube growth and chirality dependence on catalyst
      composition.
AB  - Vertical arrays of single walled carbon nanotubes (VA-SWNTs) were grown using bi
      metallic nanoparticle pro-catalysts. Iron oxide particles were doped with varying
      quantities of first row transition metals (Mn, Co, Ni, and Cu) for a comparative
      study of the growth of nanotubes. VA-CNT samples were verified using scanning
      electron microscopy, and characterized using resonance Raman spectroscopy. The
      length of the VA-CNTs is used as a measure of catalyst activity: the presence of
      dopants results in a change in the CNT length and length distribution. Cross
      correlation of the Raman spectra reveal variations in the distribution of radial
      breathing mode peaks according to the pro-catalyst composition. The formation of
      various chirality nanotubes is constant between repetitive runs with a particular
      catalyst, but may be controlled by the identity and concentration of the metal
      dopants within the iron catalyst. These results demonstrate that the composition
      of the catalyst is a major driving force toward type selective growth of
      nanotubes. 

PMID- 23974220
TI  - Lighting up silica nanotubes transcribed from the submicron structure of a metal
      peptide hybrid.
AB  - Fluorescent silica nanotubes are attracting increasing interest because of their
      versatile applicability in a range of diverse fields. By using sol-gel
      transcription of tetraethylorthosilicate (TEOS) from various soft templates,
      silica nanotubes can be conveniently prepared. Metal-peptide hybrids with well
      defined nanostructures and outstanding functionalities are very interesting
      candidates to serve as templates. Herein, we demonstrate that glutathione (GSH)
      can act as a building block for a bioinspired structure with dimensions down to
      the nanoscale, based on specific interactions between metal ions and the peptide.
      Congo red is able to selectively stain the nanofibres obtained, and appears apple
      green in colour, implying that Congo red is promising to serve as an effective
      and convenient probe for determining the self-assembly of GSH and copper ions.
      Furthermore, silica nanotubes are synthesized using the nanofibres as a template
      in a very simple way. The silica nanotubes can be lit up by biomolecule-templated
      metal nanoparticles or nanoclusters and emit bright fluorescence. This work will
      certainly open up new opportunities in fabricating a broad range of
      nanostructured materials with versatile functionalities. 

PMID- 23974221
TI  - Palisaded neutrophilic and granulomatous dermatitis associated with ankylosing
      spondylitis.
AB  - Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare neutrophilic
      dermatosis that shows a broad clinical and histopathological spectrum. The
      clinical presentation of PNGD varies from asymptomatic papules, to nodules, to
      annular plaques. The most common clinical presentation is erythematous papules on
      the extensor surface of extremities, especially fingers and elbows.
      Histopathological findings demonstrate a spectrum of changes that reflect the
      evolution of the lesions, from only sparse mixed perivascular infiltrates to
      interstitial or palisaded granuloma formation with dermal fibrosis. The cause of
      PNGD is unknown, but there is a prominent association with systemic conditions,
      particularly with autoimmune diseases, representing rheumatoid arthritis and
      systemic lupus erythematosus, the most common associations. It has also been
      described associated to systemic sclerosis, sarcoidosis, systemic vasculitis,
      inflammatory bowel disease, and lymphoproliferative disorders, and also drugs
      have been implicated. Recently, it has been described the potential association
      with tumor necrosis factor alpha inhibitors. This dermatosis should be considered
      as a marker of systemic disease and particularly it should be considered in
      patients with history of autoimmune disorders who present with papular eruptions
      on the extremities.

PMID- 23974222
TI  - Inflammatory complications related to tattooing: a histopathological approach
      based on pattern analysis.
AB  - : Although tattooing is an ancient practice, its increasing popularity and social
      acceptance, variability of tattoo ink composition, sporadic reports of novel
      tattoo reactions and advances in the field of tattoo removal techniques make it a
      topic of immense interest among dermatologists and pathologists alike. Since
      effective legislation governing the tattoo industry is largely lacking in most
      regions of the world, it is important to recognize the range of tattoo-related
      complications from a dermatopathological perspective. Using a pattern-based
      approach, this review details the broad spectrum of inflammatory reactions, which
      may be encountered in adverse reactions associated with tattooing. Awareness of
      the range of inflammatory tattoo reactions is crucial as some of these patterns
      of inflammation can be associated with systemic disorders and others may serve as
      important clues for an underlying infective condition. 

PMID- 23974218
TI  - Macrophages and CSF-1: implications for development and beyond.
AB  - Recent focus on the diversity of macrophage phenotype and function signifies that
      these trophic cells are no longer of exclusive interest to the field of
      immunology. As key orchestrators of organogenesis, the contribution of
      macrophages to fetal development is worthy of greater attention. This review
      summarizes the key functions of macrophages and their primary regulator, colony
      stimulating factor (CSF)-1, during development; highlighting trophic mechanisms
      beyond phagocytosis and outlining their roles in a range of developing organ
      systems. Advances in the understanding of macrophage polarization and functional
      heterogeneity are discussed from a developmental perspective. In addition, this
      review highlights the relevance of CSF-1 as a pleiotropic developmental growth
      factor and summarizes recent experimental evidence and clinical advancements in
      the area of CSF-1 and macrophage manipulation in reproduction and organogenic
      settings. Interrogation of embryonic macrophages also has implications beyond
      development, with recent attention focused on yolk sac macrophage ontogeny and
      their role in homeostasis and mediating tissue regeneration. The regulatory
      networks that govern development involve a complex range of growth factors,
      signaling pathways and transcriptional regulators arising from epithelial,
      mesenchymal and stromal origins. A component of the organogenic milieu common to
      the majority of developing organs is the tissue macrophage. These hemopoietic
      cells are part of the mononuclear phagocyte system regulated primarily by colony
      stimulating factor (CSF)-1 (1, 2). There is a resurgence in the field of CSF-1
      and macrophage biology; where greater understanding of the heterogeneity of these
      cells is revealing contributions to tissue repair and regeneration beyond the
      phagocytic and inflammatory functions for which they were traditionally ascribed
      (3-6). The accumulation of macrophages during tissue injury is no longer viewed
      as simply a surrogate for disease severity, with macrophages now known to be
      vital in governing tissue regeneration in many settings (7-11). In particular it
      is the influence of CSF-1 in regulating an alternative macrophage activation
      state that is increasingly linked to organ repair in a range of disease models
      (12-17). With many similarities drawn between organogenesis and regeneration, it
      is pertinent to re-examine the role of CSF-1 and macrophages in organ
      development. 

PMID- 23974223
TI  - Dermal spindle cell adenolipoma.

PMID- 23974224
TI  - Desmoplastic melanoma: expression of epithelial-mesenchymal transition-related
      proteins.
AB  - Desmoplastic melanoma (DM) is a rare variant of melanoma. Most frequently, it
      seems as clinically ambiguous and histologically characterized by a poorly
      demarcated neoplasm composed of a proliferation of spindle melanocytes dispersed
      in a prominent collagenous stroma. It often represents a diagnostic challenge,
      delaying its detection. We analyzed the expression profile of 29 (28 "pure" and 1
      "combined") DM. These data were compared with a series of 62 primary vertical
      growth phase nondesmoplastic melanomas (NDMs) using a set of proteins including
      melanocytic markers (S-100 protein and melan-A) and epithelial-mesenchymal
      transition (EMT)-related proteins (E-cadherin, N-cadherin, SPARC, WT1, and
      PKCalpha). The S-100 protein confirmed the melanocytic origin of the DM (positive
      in 96%). The significant positive expression of N-cadherin, SPARC, and WT1 in DM
      (61%, 82%, and 71%) compared with NDM (28%, 43%, and 47%; P < 0.05) and a lower
      expression of E-cadherin in DM (14%) compared with NDM (61%) support specific
      adhesive and migratory properties of DM tumor cells. The study was carried out
      with tissue microarrays that partly limited the study of the tumor sections. This
      study demonstrates, for the first time, a prominent expression of epithelial
      mesenchymal transition-related proteins in DMs and tries to be one more step in
      refining its knowledge and leading to a better understanding of its biological
      and clinical behaviors.

PMID- 23974225
TI  - Leukemia cutis coexisting with dermatofibroma as the initial presentation of B
      cell chronic lymphocytic leukemia/small lymphocytic lymphoma.
AB  - : Cutaneous involvement by chronic lymphocytic leukemia/small lymphocytic
      lymphoma (CLL/SLL) is often observed in patients with a known history of systemic
      disease. Rarely, CLL/SLL may initially present with skin lesions. There are also
      rare reports of cutaneous CLL/SLL occurring in herpes scars and as an incidental
      finding in excision specimens for carcinoma. We present a 76-year-old woman with
      an inverted conical firm papule on the upper back that was clinically suggestive
      of a dermatofibroma. Excisional biopsy demonstrated the presence of a
      dermatofibroma coexisting with CLL/SLL. We describe the rare occurrence of
      CLL/SLL initially presenting as leukemia cutis. In addition, to the best of our
      knowledge, this is the first report of dermatofibroma coexisting with CLL/SLL.
      This finding further expands the types of skin lesions that may coincide with
      CLL/SLL. 

PMID- 23974227
TI  - Quantitative phase imaging of living cells: application of the phase volume and
      area functions to the analysis of "nucleolar stress".
AB  - We applied coherent phase microscopy to develop a method of quantitative
      evaluation of functional state of eukaryotic cells using the coordinates of
      characteristic points (CP) in the functions of the phase volume W and area S. In
      a fragment of a single cell image (HCT116 human colon carcinoma cell line) with
      detectable nucleolus, the values of the phase thickness, area, and volume were
      calculated. These values dramatically changed within the initial minutes of cell
      exposure to the transcriptional inhibitor actinomycin D. The positions of CP in
      the graphs of S and W functions allowed for monitoring the time-dependent
      decrease of nucleolar contrast, a major optical hallmark of "nucleolar stress."
      Given that the area and volume functions reflect optical heterogeneity of the
      cell and are independent of its optical model, these functions can be applicable
      as general mathematical tools for the analysis of cell morphology and physiology.

PMID- 23974226
TI  - Configurations of early risk and their association with academic, cognitive,
      emotional and behavioural outcomes in middle childhood.
AB  - PURPOSE: Risk factors for children's development are multifarious and co-occur,
      having cumulative as well as individual impacts. Yet common configurations of
      early childhood risks remain little understood. The current study aimed to
      identify patterns of early risk exposure and to examine their relationship with
      diverse outcomes in middle childhood. METHODS: Using latent class analysis in a
      large, community-based, UK sample (N = 13,699), we examined 13 putative risk
      factors to identify patterns of exposure. RESULTS: Four risk configurations were
      identified: low (65 %), socio-demographic (14 %), family dysfunction (12 %), and
      multiple (9 %) risk classes. As expected, children in the low risk group fared
      best on all outcome measures, and those with multiple risk, worst. Importantly,
      specificity in associations with outcomes emerged, such that cognitive outcomes
      were predominantly linked with socio-demographic adversities, emotional
      difficulties with family dysfunction, and conduct problems increased across risk
      classes. CONCLUSIONS: Better understanding of configurations of childhood risk
      exposures may help to target resources for children in need.

PMID- 23974228
TI  - Prevention of preterm delivery with compounded 17a-hydroxyprogesterone caproate.
AB  - 17a-hydroxyprogesterone caproate is a naturally occurring metabolite of
      progesterone that is produced in significant quantities during pregnancy. The
      demand for 17a-hydroxyprogesterone caproate, the lack of a commercially available
      manufactured form approved by the US Food And Drug Administration, and
      publication of the results of a large trial to determine the effectivenss of the
      drug in the prevention of preterm delivery have spawned an increased interest in
      compounded formulations of the drug. The demand also has necessitated a review of
      the available literature and of past clinical studies, and a look at present and
      planned studies. Owing to the importance of this drug in pregnancy and the need
      for safety, accuracy in potency, and sterility in an intramuscular injection (the
      most common route of administration), compounding pharmacies must be in
      compliance with the United States Pharmacopeia Chapter 797 standards should they
      wish to compound this formulation. 

PMID- 23974229
TI  - Case report: hydroxyprogesterone caproate injection for prevention of preterm
      labor.

PMID- 23974230
TI  - The role of drug promotion in the prescription of hormone replacement therapy in
      the United States.
AB  - Prior to 1980, almost all drug advertising was direted to physicians, the parties
      responsible for prescribing medications to patients. Beginning in 1980, however,
      drug companies began advertising directly to patients by various means,
      specifically television and print adversisements and sponsorship of sports and
      similar events. During the last decade, as computers have become a common
      household item, the Internet is now another source of advertising for drug
      manufacturers. This change in advertising has been effective, since research has
      demonstrated that physicians' prescribing decisions are, in fact, influenced
      heavily by patients' requests for specific medications. In 1997, the US Food and
      Drug Administration devised specific guidelines for the television advertising of
      drugs produced by pharmaceutical manufacturers. Since youth and beauty have long
      been valued feminine qualities in the US, where menopausal women are assumed to
      suffer most from the effects of aging, pharmaceutical companies targeted women
      for the promotion of hormone-containing drugs that were purported to minimize the
      effects of menopause and ensure better health. As a result, advertising has
      played a key role in the prescribing of hormone replacement therapy in the US for
      the last 60 years. Since many of the advertised benefits of hormone replacement
      therapy are never realized by the patient, and the hazards of treatment are often
      minimized, it remains the responsibility of clinicians to safeguard their
      patients' health by basing the decision to prescribe on valid scientific evidence
      rather than the message of an advertising pitch. 

PMID- 23974231
TI  - Patient satisfaction with pharmacist intervention and consultation in hormone
      replacement therapy: an update.
AB  - The purpose of this study was to assess whether the satisfaction of women who
      took part in the pharmacist-administered bioidentical hormone replacement therapy
      consultation service at an urban compounding pharmacy has improved since
      implementation of a follow-up call program. A questionnaire was mailed to 200
      randomly selected women who completed hormone replacement therapy consultation
      and received all three follow-up calls from the pharmacy during the period from
      July 22, 2003, to April 22, 2004. The returned surveys were tabulated and
      analyzed, and independent t-tests were used to compare data collected in 2001
      with that collected in 2004 on questionnaire items of interest. Of the 200
      surveys sent out to patients, 125 were returned completed (a response rate of
      62.5%). Over 50% of the respondents heard about the hormone replacement therapy
      program through referral from their healthcare provider, and 34.4% from a friend
      or a relative. A large majority (95.9%) of the respondents either agreed or
      strongly agreed that the follow-up calls were helpful; however, only 73.8% felt
      comfortable discussing their concerns with student interns, who were responsible
      for making the follow-up calls. Most (95.2) of the respondents reported no new
      health conditions since initiation of natural hormone replacement therapy. The t
      tests revealed improvement in patient satisfaction items between 2001 and 2004,
      indicating that patient satisfaction with the consultation service improved from
      2001 to 2004, and most of the differences were statistically significant (P less
      than 0.05). The survey results also showed that participants were happy about the
      follow-up calls, which perhaps contributed to the increase in satisfaction. 

PMID- 23974232
TI  - Probiotic therapy-part 2: clinical perspectives.
AB  - In this second of a two-part series, the efficacy of probiotic treatment is
      discussed by a pediatric gastroenterologist and a compounding pharmacist, who,
      with patients and caregivers, have tailored many probiotic regimens to a
      successful outcome. Although the mechanisms of action for probiotics remain
      unclear, the benefits of probiotics therapy are being documented increasingly in
      case reports, research studies, and randomized controlled trials. Recommending
      treatment that is not helpful could, to a degree, be harmful, and thus published
      data should be reviewed when a probiiotic supplement is selected. Patients may
      require information on the therapeutic effectiveness and safety of probiiotics,
      and pharmacists should have such information available. Although there are
      manufactured probiotic supplements, innovative compounding enables pharmacists to
      offer their clients novel dosage forms. The future of probiotic therapy includes
      the possibility of genetically engineered probiotic bacterial strains that exert
      target effects in the gut and an increase in available probiotic formulations for
      compounding pharmacists to offer their clients. 

PMID- 23974233
TI  - Quality-Control Analytical Methods: Particulate Matter In Injections: What is It
      and What are the Concerns?
AB  - The presence of particulate matter in intravenous injections, especially in large
      numbers, represents a potentially life-threatening health hazard. The United
      States Pharmacopeia has established procedures and standards to ensure the
      quallity of intravenous injections, including particulate counts. Compounding
      pharmacists can reduce the incidence of adverse events in patients by assuring
      the quality of their preparations through filtration of intravenous preparations
      and analytical testing procedures.

PMID- 23974234
TI  - Basics of compounding for dentistry, part 2: tooth whitening.
AB  - The most commonly prescribed cosmetic dental procedure is tooth whitening. Many
      manufacturers are involved in the development and sale of at-home tooth-whitening
      products that have been approved by the American Dental Association. However, the
      American Academy for Cosmetic Dentistry recommends dentist-supervised treatments.
      There are various causes for tooth discoloration and various formulas that can be
      compounded for tooth bleaching. Compounding pharmacists should increase their
      knowledge of the types and origins of tooth discoloration, bleaching techniques,
      and the advantages and disadvantages of tooth bleaching so that they can better
      serve their patients and be involved in this growing market. 

PMID- 23974235
TI  - Contolled environment testing association applications guide for the use of
      barrier isolators in compounding sterile preparations in healthcare facilities,
      part 2.
AB  - The Controlled Environment Testing Association guide focuses on isolator
      applications that are appropriate for use in facilities that compound sterile
      preparations. Owing to the fact that there are no uniform industry standards for
      the manufacture of barrier isolators, the purpose of this guide is to increase
      pharmacists' awareness of the need to establish procedures addressing issues
      unique to isolators. In the future, Controlled Envrironment Testing Association
      will publish a guide-not a testing "standard"-for industry procedures for testing
      and commissioning isolators, as no published industry procedures are available at
      this time. 

PMID- 23974236
TI  - Compatibility of micafungin injection with other drugs during simulated y-site co
      administration.
AB  - The objective of this study was to evaluate the physical compatibility of
      micafungin injection with selected other drugs during simulated Y-site co
      administration. Physical stability was assessed by both visual observation and
      turbidity measurement. Micafungin in 0.9% sodium chloride injection was combined
      with each of 48 other drugs, including antineoplastics, analgesics, anti
      infectives, and supportive care drugs undiluted or diluted in 0.9% sodium
      chloride injection, and with a parenteral nutrition admixture. Visual
      examinations were performed with the unaided eye in fluorescent light and by
      using a Tyndall beam, and the turbidity of each sample was measured. The samples
      were evaluated immediately after mixing and again 1 and 4 hours after
      preparation. Twenty-nine of the drugs tested were found to be compatible for at
      least 4 hours. The measured turbidity of the micafungin control solutions and the
      compatible test samples remained essentially unchanged throughout the study. The
      other 19 drugs exhibited frank precipitation, microparticulate formation or
      unacceptable increases in turbidity within 4 hours of mixture with micafungin and
      thus should not be administered simultaneously via Y-site with micafungin. 

PMID- 23974237
TI  - Physical and chemical stability of palonosetron hydrochloride with dacarbazine
      and with methylprednisolone sodium succinate during simulated y-site
      administration.
AB  - The objective of this study was to evaluate the physical and chemical stability
      of mixtures of undiluted palonosetron hydrochloride 50 micrograms/mL with
      dacarbazine 4 mg/mL and with methylprednisolone sodium succinate 5 mg/mL in 5%
      dextrose injection during simulated Y-site administration. Triplicate test
      samples were prepared by admixing 7.5 mL of palonosetron hydrochloride with 7.5
      mL of dacarbazine solution and, separately, methylprednisolone sodium succinate
      solution. Physical stability was assessed by using a multistep evaluation
      procedure that included both turbidimetric and particulate measurement as well as
      visual inspection. Chemical stability was assessed by using stability-indicating
      high-performance liquid chromatographic analytical techniques that determined
      drug concentrations. Evaluations were performed immediately after mixing and 1
      and 4 hours after mixing. The palonosetron hydrochloride-dacarbazine samples were
      clear and colorless when viewed in normal fluorescent room light and when viewed
      with a Tyndall beam. Measured turbidities remained unchanged; particulate
      contents were low and exhibited little change. High-performance liquid
      chromatography analysis revealed that palonosetron hydrochloride and dacarbazine
      remained stable throughout the 4-hour test with no drug loss. Palonosetron
      hydrochloride is, therefore, physically compatible and chemically stable with
      dacarbazine during Y-site administration. Within 4 hours, the mixtures of
      palonosetron hydrochloride and methylprednisolone sodium succinate developed a
      microprecipitate that became a white precipitate visible to the unaided eye. The
      precipitate was analyzed and identified as methylprednisolone. Palonosetron
      hydrochloride is incompatible with methylprednisolone sodium succinate. 

PMID- 23974238
TI  - Chemical stability of diphenhydramine hydrochloride from an elixir and lidocaine
      hydrochloride from a viscous solution when mixed together.
AB  - The stability of diphenhydramine hydrochloride (from an elixir) and lidocaine
      hydrochloride (from a viscous solution) in a mixture (1:1) was studied using a
      stability-indicating high-peformance liquid chromatographic assay method. The
      concentrations of the drugs were related directly to peak heights and the percent
      relative standard deviations based on five injections were 1.4 for
      diphenhydramine and 1.3 for lidocaine. The products of hydrolysis from the both
      the drugs and a number of excipients present in the dosage forms did not
      interfere with the developed assay procedure. The mixture was stable for at least
      21 days when stored in amber-colored bottles at room temperature. The pH value of
      the mixture remained constant, and the physical appearance did not change during
      the study period. 

PMID- 23974239
TI  - Particle correlations and evidence for dark state condensation in a cold dipolar
      exciton fluid.
AB  - Dipolar excitons are long-lived quasi-particle excitations in semiconductor
      heterostructure that carry an electric dipole. Cold dipolar excitons are expected
      to have new quantum and classical multi-particle correlation regimes, as well as
      several collective phases, resulting from the intricate interplay between the
      many-body interactions and their quantum nature. Here we show experimental
      evidence of a few correlation regimes of a cold dipolar exciton fluid, created
      optically in a semiconductor bilayer heterostructure. In the higher temperature
      regime, the average interaction energy between the particles shows a surprising
      temperature dependence, which is evidence for correlations beyond the mean field
      model. At a lower temperature, there is a sharp increase in the interaction
      energy of optically active excitons, accompanied by a strong reduction in their
      apparent population. This is evidence for a sharp macroscopic transition to a
      dark state, as has been suggested theoretically. 

PMID- 23974240
TI  - Counting glycans revisited.
AB  - We present an algorithm for counting glycan topologies of order n that improves
      on previously described algorithms by a factor n in both time and space. More
      generally, we provide such an algorithm for counting rooted or unrooted d-ary
      trees with labels or masses assigned to the vertices, and we give a "recipe" to
      estimate the asymptotic growth of the resulting sequences. We provide constants
      for the asymptotic growth of d-ary trees and labeled quaternary trees (glycan
      topologies). Finally, we show how a classical result from enumeration theory can
      be used to count glycan structures where edges are labeled by bond types. Our
      method also improves time bounds for counting alkanes.

PMID- 23974241
TI  - Peer attachment formation by systemic redox regulation with social training after
      a sensitive period.
AB  - Attachment formation is the most pivotal factor for humans and animals in the
      growth and development of social relationships. However, the developmental
      processes of attachment formation mediated by sensory-motor, emotional, and
      cognitive integration remain obscure. Here we developed an animal model to
      understand the types of social interactions that lead to peer-social attachment
      formation. We found that the social interaction in a sensitive period was
      essential to stabilise or overwrite the initially imprinted peer affiliation
      state and that synchronised behaviour with others based on common motivations
      could be a driver of peer social attachment formation. Furthermore, feeding
      experience with supplementation of ubiquinol conferred peer social attachment
      formation even after the sensitive period. Surprisingly, the experience of
      feeding beyond the cage window was also effective to reduce the required amount
      ubiquinol, suggesting that peri-personal space modulation may affect socio
      emotional cognition and there by lead to attachment formation. 

PMID- 23974242
TI  - Regulation of histone gene transcription in yeast.
AB  - Histones are the primary protein component of chromatin, the mixture of DNA and
      proteins that packages the genetic material in eukaryotes. Large amounts of
      histones are required during the S phase of the cell cycle when genome
      replication occurs. However, ectopic expression of histones during other cell
      cycle phases is toxic; thus, histone expression is restricted to the S phase and
      is tightly regulated at multiple levels, including transcriptional, post
      transcriptional, translational, and post-translational. In this review, we
      discuss mechanisms of regulation of histone gene expression with emphasis on the
      transcriptional regulation of the replication-dependent histone genes in the
      model yeast Saccharomyces cerevisiae. 

PMID- 23974243
TI  - The cyclin-dependent kinase family in the social amoebozoan Dictyostelium
      discoideum.
AB  - Cyclin-dependent kinases (Cdk) are a family of serine/threonine protein kinases
      that regulate eukaryotic cell cycle progression. Their ability to modulate the
      cell cycle has made them an attractive target for anti-cancer therapies. Cdk
      protein function has been studied in a variety of Eukaryotes ranging from yeast
      to humans. In the social amoebozoan Dictyostelium discoideum, several homologues
      of mammalian Cdks have been identified and characterized. The life cycle of this
      model organism is comprised of a feeding stage where single cells grow and divide
      mitotically as they feed on their bacterial food source and a multicellular
      developmental stage that is induced by starvation. Thus it is a valuable system
      for studying a variety of cellular and developmental processes. In this review I
      summarize the current knowledge of the Cdk protein family in Dictyostelium by
      highlighting the research efforts focused on the characterization of Cdk1, Cdk5,
      and Cdk8 in this model Eukaryote. Accumulated evidence indicates that each
      protein performs distinct functions during the Dictyostelium life cycle with Cdk1
      being required for growth and Cdk5 and Cdk8 being required for processes that
      occur during development. Recent studies have shown that Dictyostelium Cdk5
      shares attributes with mammalian Cdk5 and that the mammalian Cdk inhibitor
      roscovitine can be used to inhibit Cdk5 activity in Dictyostelium. Together,
      these results show that Dictyostelium can be used as a model system for studying
      Cdk protein function. 

PMID- 23974245
TI  - Comment on: fibronectin in tissue regeneration: timely disassembly of the
      scaffold is necessary to complete the build.

PMID- 23974244
TI  - Sequential inactivation of Rho GTPases and Lim kinase by Pseudomonas aeruginosa
      toxins ExoS and ExoT leads to endothelial monolayer breakdown.
AB  - Pseudomonas aeruginosa is a major human opportunistic pathogen and one of the
      most important causal agents of bacteremia. For non-blood-borne infection,
      bacterial dissemination requires the crossing of the vascular endothelium, the
      main barrier between blood and the surrounding tissues. Here, we investigated the
      effects of P. aeruginosa type 3 secretion effectors, namely ExoS, ExoT, and ExoY,
      on regulators of actin cytoskeleton dynamics in primary endothelial cells. ExoS
      and ExoT similarly affected the Lim kinase-cofilin pathway, thereby promoting
      actin filament severing. Cofilin activation was also observed in a mouse model of
      P. aeruginosa-induced acute pneumonia. Rho, Rac, and Cdc42 GTPases were
      sequentially inactivated, leading to inhibition of membrane ruffling, filopodia,
      and stress fiber collapse, and focal adhesion disruption. At the end of the
      process, ExoS and ExoT produced a dramatic retraction in all primary endothelial
      cell types tested and thus a rupture of the endothelial monolayer. ExoY alone had
      no effect in this context. Cell retraction could be counteracted by
      overexpression of actin cytoskeleton regulators. In addition, our data suggest
      that moesin is neither a direct exotoxin target nor an important player in this
      process. We conclude that any action leading to inhibition of actin filament
      breakdown will improve the barrier function of the endothelium during P.
      aeruginosa infection. 

PMID- 23974246
TI  - Author's reply to: Comment on: Fibronectin in tissue regeneration: timely
      disassembly of the scaffold is necessary to complete the build.

PMID- 23974247
TI  - Physical and photoelectrochemical properties of Zr-doped hematite nanorod arrays.
AB  - This work examines the effect of Zr(4+) ions on the physical and
      photoelectrochemical (PEC) properties of hematite (alpha-Fe2O3) nanorod arrays
      grown in an aqueous solution containing zirconyl nitrate (ZrO(NO3)2) as a dopant
      precursor. The concentration of ZrO(NO3)2 in the precursor solution influenced
      both the film thickness and the Zr(4+) concentration in the resulting films. Zr
      doping was found to enhance the photocurrent for water splitting; the highest
      photocurrent at 1.0 V vs. Ag/AgCl (0.33 mA cm(-2)) for the Zr-doped alpha-Fe2O3
      film was approximately 7.2 times higher than that for the undoped film (0.045 mA
      cm(-2)). Additionally, the incident photon to current efficiency (IPCE) at 360 nm
      and 1.23 V vs. the reversible hydrogen electrode (RHE) increased from 3.8% to
      13.6%. Ultrafast transient absorption spectroscopy suggests that Zr doping may
      influence PEC performance by reducing the rate of electron-hole recombination. 

PMID- 23974249
TI  - Dynamics and dimension of an amyloidogenic disordered state of human beta(2)
      microglobulin.
AB  - Human beta2-microglobulin (beta2m) aggregation is implicated in dialysis-related
      amyloidosis. Previously, it has been shown that beta2m adopts an ensemble of
      partially unfolded states at low pH. Here we provide detailed structural and
      dynamical insights into the acid unfolded and yet compact state of beta2m at pH
      2.5 using a host of fluorescence spectroscopic tools. These tools allowed us to
      investigate protein conformational dynamics at low micromolar protein
      concentrations in an amyloid-forming condition. Our equilibrium fluorescence data
      in combination with circular dichroism data provide support in favor of
      progressive structural dissolution of beta2m with lowering pH. The acid unfolded
      intermediate at pH 2.5 has high 8-anilinonaphthalene, 1-sulfonic acid (ANS)
      binding affinity and is devoid of significant secondary structural elements.
      Using fluorescence lifetime measurements, we have been able to monitor the
      conformational transition during the pH transition from the native to the compact
      disordered state. Additionally, using time-resolved fluorescence anisotropy
      measurements, we have been able to distinguish this compact disordered state from
      the canonical denatured state of the protein by identifying unique dynamic
      signatures pertaining to the segmental chain mobility. Taken together, our
      results demonstrate that beta2m at pH 2.5 adopts a compact noncanonical unfolded
      state resembling a collapsed premolten globule state. Additionally, our stopped
      flow fluorescence kinetics results provide mechanistic insights into the
      formation of a compact disordered state from the native form. 

PMID- 23974248
TI  - Life-Threatening Cryoglobulinemic Patients With Hepatitis C: Clinical Description
      and Outcome of 279 Patients.
AB  - Cryoglobulinemia is characterized by a wide range of causes, symptoms, and
      outcomes. Hepatitis C virus (HCV) infection is detected in 30%-100% of patients
      with cryoglobulins. Although more than half the patients with cryoglobulinemic
      vasculitis present a relatively benign clinical course, some may present with
      potentially life-threatening situations. We conducted the current study to
      analyze the clinical characteristics and outcomes of HCV patients presenting with
      life-threatening cryoglobulinemic vasculitis. We evaluated 181 admissions from 89
      HCV patients diagnosed with cryoglobulinemic vasculitis consecutively admitted to
      our department between 1995 and 2010. In addition, we performed a systematic
      analysis of cases reported to date through a MEDLINE search.The following organ
      involvements were considered to be potentially life-threatening in HCV patients
      with cryoglobulinemic vasculitis: cryoglobulinemic, biopsy-proven
      glomerulonephritis presenting with renal failure; gastrointestinal vasculitis;
      pulmonary hemorrhage; central nervous system (CNS) involvement; and myocardial
      involvement. A total of 279 patients (30 from our department and 249 from the
      literature search) fulfilled the inclusion criteria: 205 presented with renal
      failure, 45 with gastrointestinal vasculitis, 38 with CNS involvement, 18 with
      pulmonary hemorrhage, and 3 with myocardial involvement; 30 patients presented
      with more than 1 life-threatening cryoglobulinemic manifestation. There were 146
      (52%) women and 133 (48%) men, with a mean age at diagnosis of cryoglobulinemia
      of 54 years (range, 25-87 yr) and a mean age at life-threatening involvement of
      55 years (range, 25-87 yr). In 232 (83%) patients, life-threatening involvement
      was the first clinical manifestation of cryoglobulinemia. Severe involvement
      appeared a mean of 1.2 years (range, 1-11 yr) after the diagnosis of
      cryoglobulinemic vasculitis. Patients were followed for a mean of 14 months
      (range, 3-120 mo) after the diagnosis of life-threatening cryoglobulinemia. Sixty
      three patients (22%) died. The main cause of death was sepsis (42%) in patients
      with glomerulonephritis, and cryoglobulinemic vasculitis itself in patients with
      gastrointestinal, pulmonary, and CNS involvement (60%, 57%, and 62%,
      respectively). In conclusion, HCV-related cryoglobulinemia may result in
      progressive (renal involvement) or acute (pulmonary hemorrhage, gastrointestinal
      ischemia, CNS involvement) life-threatening organ damage. The mortality rate of
      these manifestations ranges between 20% and 80%. Unfortunately, this may be the
      first cryoglobulinemic involvement in almost two-thirds of cases, highlighting
      the complex management and very elevated mortality of these cases.

PMID- 23974255
TI  - Introduction to hospital compounding.
AB  - The practice of compounding in both the community and hospital pharmacy settings
      has undergone constant change since the 1980s. Although standards and guidelines
      have been established, additional standards and guidelines are being developed to
      ensure that compounded preparations are of high quality. Although hospital
      compounding and community compounding have some differences in their pracitce,
      both must comply with the standards for drug preparations set forth by the United
      States Pharmacopeial Convention. The strict standards published in 2003 by the
      United States Pharmacopeial Convention in the area of sterile compounding have
      become a major concern for hospital pharmacies, which have been given an extended
      compliance date of January 1, 2008, by the Joint Commission on Accreditation of
      Healthcare Organizations. Because of the high standards for the practice of
      compounding and the new, complex dosage forms that are being prescribed to meet
      patients' individual needs, pharmacists and technicians involved in compounding
      need to have additional training to learn these new compounding skills and
      quality assurance techniques. 

PMID- 23974256
TI  - Training and competency considerations for pharmacies providing compounded
      sterile preparations.
AB  - Quality is paramount to compounding and dispensing of compounded sterile
      preparations, and effective staff training is the single most important factor in
      ensuring quality outcomes. Successful training programs are based on four
      precursors, namely core knowledge; operational principles of the individual
      pharmacy; external requirements, such as those of state pharmacy boards and the
      United States Pharmacopeia; and pharmacy-specific policies and procedures. If
      properly detailed and customized to the specific pharmacy, policies and
      procedures can be used as a training tool. To be most effective, training for
      pharmacy personnel should be based on the principles of adult learning theory,
      which emphasize acquisition of practical knowldege and skills as the trainee
      needs to know them. Competency assessment should focus on both basic skills and
      developmental activities and can be accomplished by traditional checklists or by
      alternative techniques such as performance monitoring, mock audits, exemplars,
      and presentations to other staff. 

PMID- 23974250
TI  - Association between the development of diabetic foot and serum fetuin-A levels.
AB  - INTRODUCTION: Fetuin-A is a glycoprotein secreted from hepatocytes, which affects
      diabetes and peripheral arterial disease. However, there has been no studies
      regarding the relation between diabetic foot and fetuin-A levels. OBJECTIVES: We
      aimed to analyze the association between diabetic foot development and serum
      fetuin-A levels. PATIENTS AND METHODS: Following the approval of the local
      ethical board, 137 patients were included in the study. Patients were divided
      into 3 groups: diabetes group (n = 49), diabetic foot group (n = 57), and control
      group (n = 31). In all patients, serum fetuin-A, C-reactive protein, magnesium,
      and hemoglobin A1c (HbA1c) levels were measured. Diabetic foot wounds were
      classified according to the Wagner classification and lower extremity arteries
      were evaluated by ultrasonography. RESULTS: Median fetuin-A levels in patients
      with diabetic foot were significantly higher than in those with diabetes.
      However, the differences in HbA1c levels between both groups were not
      statistically significant. A positive correlation was found between the Wagner
      classification and ultrasound evaluation of the peripheral arteries (degree of
      atherosclerosis) in patients with diabetic foot. In the diabetic foot group,
      fetuin-A levels were also found to be positively correlated with ultrasound
      evaluation. CONCLUSIONS: We observed a positive correlation between serum fetuin
      A levels and the development of diabetic foot.

PMID- 23974257
TI  - Putting the science back into the "art and science" of compounding.
AB  - Acceptance of the revised standards for compounding sterile preparations
      published as United States Pharmacopeia Chapter 797 has met with a significant
      amount of resistance, mainly owing to the expense of compliance. These standards
      owe much to the expanded perspective of the United States Pharmacopeia Council of
      Experts Sterile Compounding Committee, which was responsible for the revision.
      Because it is widely accepted by those in the pharmaceutical industry that
      compounding facility design, environmental control, and personnel have direct
      effects on the sterility of aseptically compounded preparations, the committee
      drew from expertise in pharmacy as well as fields outside pharmacy, such as
      microbiology, infection control, and engineering controls. How "science" from
      other disciplines has been incorporated into the in-process revision of United
      States Pharmacopeia Chapter 797 is reviewed. 

PMID- 23974258
TI  - Compounded treatment options for cystitis and other bladder problems.
AB  - Few large-scale studies are available from which to develop treatment options for
      chronic bladder problems such as interstitial cystitis and refractory detrusor
      hyper-reflexia. Thus many urologists must rely on case reports and smaller
      studies to develop alternative treatment options. Moreover, the etiology and
      pathophysiology of interstitial cystitis are not understood. One of the few
      available treatment options is intravesical therapies, which have the benefit of
      little systemic absorption and, therefore, few side effects. Intravesical
      solutions must be compounded according to United States Pharmacopeia Chapter 797
      sterile compounding guidelines, and the short beyond-use date of such
      preparations can be problematic. Compounding pharmacists can work with urologists
      to provide safe, effective treatments that will ultimately improve the patient's
      quality of life. 

PMID- 23974259
TI  - Teaching lab renovation: university of Texas at austin college of pharmacy
      combines sterile and nonsterile compounding lab spaces.
AB  - Compounding of both sterile and nonsterile preparations must be accomplished in
      laboratory facilities that meet or exceed the standards set forth by the United
      States Pharmacopeia. Although educational institutions that teach courses in
      compounding sterile and nonsterile preparations ideally should include these
      standards in their curriculum and meet these standards, many of the existing
      laboratories in colleges of pharmacy were constructed before United States
      Pharmacopeia Chapter 797 was initiated. Some colleges of pharmacy that were
      dedicated strictly to instruction on nonsterile preparations are attempting to
      achieve the primary objectives of United States Pharmacopeia Chapter 797 by
      adapting their laboratories into an environment that meets standards for sterile
      preparations. In many cases, such renovations are being performed with limited
      funding. The University of Texas at Austin College of Pharmacy has conducted such
      a renovation; its goals and future plans, as well as the obstacles and costs of
      the construction, are presented here. Although the university had no available
      space for installation of a facility compliant with United sTates Pharmacopeia
      Chapter 797, it was able to provide an environment that would temporariy
      accommodate both sterile and nonsterile compounding until such time as the
      facility can be made more compliant. 

PMID- 23974260
TI  - Quality-control analytical methods: a guide to quality control testing for the
      compounding pharmacist.
AB  - Testing procedures must be in place for pharmacies that compound sterile and
      nonsterile preparations, and any such procedures must meet the standards set
      forth in United states Pharmacopeia Chapters 795 and 797, as well as other
      related chapters. Having written procedures that meet the standards of the United
      States Pharmacopeia not only aids in assuring the safety of the patients who use
      these preparations, but also provides some protection for the pharmacy should
      quality control/quality assurance issues be questioned by regulatory authorites.
      A pharmacy also must consider its state board of pharmacy regulations when
      setting up its procedures. To provide guidance in potency testing of sterile and
      nosterile preparations, a compounding pharmacy should consider having a standard
      operating procedure in place. 

PMID- 23974261
TI  - Hospice symptom relief kit: an update.
AB  - A hospice patient's condition can change quickly and dramatically. Because of the
      unpredictability of sudden changes in a hospice patient's pain and other
      symptoms, planning ahead is essential when it comes to preventing needless
      suffering. To be prepared for such changes, the author developed what was
      originally called the Hospice Emergency Kit, which has now been more
      appropriately renamed the Symptom Relief Kit. The rationale for the kit is to
      have patient-specific medications ready and readily available before the patient
      actually needs them. Having these kits available allows hospice care providers to
      treat their patients with the dignity and care they deserve. 

PMID- 23974262
TI  - Innovations in compounding: integrated barcode system verifies chemical identity,
      weight.
AB  - Two of a compounder's greatest concerns are confirming the identity of a drug
      used in a compound and verifying the weight of that drug before it is
      incorporated into a custom preparation. Bill Mixon, RPh, owner of The Compounding
      Pharmacy in Hickory, North Carolina, has devised a computerized network
      consisting of an electronic balance, a thermal label printer, and a barcode
      system that enables fellow compounders to ensure the accuracy of chemical weights
      and drug labeling. Most compounders work with more than one vendor, and most
      vendors do not barcode their chemicals, but Mixon's system enables the compounder
      to barcode the chemicals from a variety of vendors. Most importantly, his system
      has prevented errors in compounding. 

PMID- 23974263
TI  - Aseptic Compounding in New Zealand and the use of Still Air Boxes.
AB  - Toward the end of the 1980s the care of terminally ill patients in New Zealand
      moved from state-owned hospitals into community hospice settings. As a result,
      repsonsibility for the management of medicines for patients receiving palliative
      care also transferred to the comunity hospice environment. To meet the
      requirements of palliative care patients and to facilitate the compounding of
      sterile preparations, community pharmacists began to compound certain aseptic
      preparations with a Still Air Box, a unique apparatus that is an alternative to
      the more expensive and bulky laminar airflow cabinets.

PMID- 23974264
TI  - Physical assessments of lipid injectable emulsions via microscopy: a comparison
      to methods proposed in United States pharmacopeia chapter 729.
AB  - In confirming the stability of lipid injectable emulsions, the United States
      Pharmacopeia has recently recommended that light scattering be used to determine
      the mean droplet size (i.e., fineness of the dispersion), and light obscuration
      or light extinction be used to quantify the extent of the large-diameter tail
      (i.e., coarseness of the dispersion). In confirming the results obtained by these
      two methods, the usefulness of a third method, differential interference contrast
      microscopy using an oil immersion technique was investigated. The physical
      stabilities of 95 different formulations made from 20% w/v lipid emulsions were
      evaluated by all three methods. A wide spectrum of globule-size distributions was
      investigated, measured by light obscuration and expressed as the volume-weighted
      percent of fat greater than 5 micrometers (PFAT5) from very fine (0.001%) to very
      coarse (0.596%) formulations. The responses obtained by the light scattering
      method did not reflect the values for the large-diameter tail (i.e., coalescence)
      seen with the less stable emulsions, whereas these differences were detectable
      using the differential interference contrast microscopy technique. It was
      concluded that differential interference contrast microscopy provides
      complementary data about the physical stability of lipid injectable emulsions and
      can be applied as a confirmatory evaluation to the methods proposed in United
      States Pharmacopeia Chapter 729. 

PMID- 23974265
TI  - Stability of memantine in an extemporaneously prepared oral liquid.
AB  - Memantine, a N-methyl-D-aspartate receptor antagonist, was recently approved by
      the United States Food and Drug Administration for the palliative treatment of
      moderate to severe Alzheimer's disease. Its suggested mechanism of action in the
      treatment of Alzheimer's disease is binding to N-methyl-D-aspartate receptors,
      which results in inhibition of glutamate activity. Glutamate has been reported to
      contribute to the pathogenesis of Alzheimer's disease by overstimulating the N
      methyl-D-aspartate receptors, resulting in brain cell damage. The stability of
      memantine in an extemporaneously prepared oral liquid was studied. An aqueous
      liquid formulation was prepared by reconstituting memantine powder from
      triturated tablets with deionized water. The expected memantine concentration was
      0.166 mg/mL. The memantine liquid was transferred into two glass prescription
      bottles; one was stored at room temperature (25 deg C), and the other in the
      refrigerator (2 deg C). Aliquots from each bottle were analyzed in quadruplicate
      on days 0, 1, 2, 3, 4, 7, 14 and 28 by using a gas chromatograph-mass
      spectrometer. The results of this study indicate that the extemporaneously
      prepared memantine oral liquid was stable for up to 7 days at room temperature
      and up to 28 days in the refrigerator. 

PMID- 23974266
TI  - Chemical Stability of Pyridoxine Hydrochloride 100-mg/mL Injection, Preservative
      Free.
AB  - This study investigated the chemical stability of pyridoxine hydrochloride
      injection (100 mg/mL) in sterile water for injection (preservative free) stored
      at 25 deg C in disposable polypropylene syringes of various sizes. The United
      States Pharmacopeia-National Formulary colorimetric assay method was used. The
      method is accurate and precise, with a percent relative standard deviation of 1.0
      based on five readings. The injection was stable for at least 180 days (no
      decomposition). The pH value of the injection remained constant at 2.4, and the
      physical appearance of the injection remained clear throughout the study period.
      The sterility of the injection at various intervals was not determined. 

PMID- 23974267
TI  - Bromophenyl functionalization of carbon nanotubes: an ab initio study.
AB  - We study the thermodynamics of bromophenyl functionalization of carbon nanotubes
      with respect to diameter and metallic/insulating character using density
      functional theory (DFT). On the one hand, we show that the functionalization of
      metallic nanotubes is thermodynamically favoured over that of semiconducting
      ones, in agreement with what binding energy calculations previously suggested. On
      the other hand, we show that the activation energy for the grafting of a
      bromophenyl molecule onto a semiconducting zigzag nanotube ranges from 0.72 to
      0.75 eV without any clear diameter dependence within numerical accuracy. This
      implies that this functionalization is not selective with respect to diameter at
      room temperature, which explains the contradictory experimental selectivities
      reported in the literature. This contrasts with what is suggested by the clear
      diameter dependence of the binding energy of a single bromophenyl molecule, which
      ranges from 1.52 eV for an (8, 0) zigzag nanotube to 0.83 eV for a (20, 0) zigzag
      nanotube. Also, attaching a single bromophenyl to a nanotube creates states in
      the gap close to the functionalization site. It therefore becomes energetically
      favourable for a second bromophenyl to attach close to the first one on
      semiconducting nanotubes. The para configuration is found to be favoured for
      resulting bromophenyl pairs and their binding energy is found to decrease with
      increasing diameter, ranging from 4.35 eV for a (7, 0) nanotube to 2.26 eV for a
      (29, 0) nanotube. An analytic form for this radius dependence is derived using a
      tight binding Hamiltonian and first order perturbation theory. The 1/R(2)
      dependence obtained (where R is the nanotube radius) is verified by our DFT
      results within numerical accuracy. Finally, bromophenyl pairs are shown to be
      favoured by only 50 meV with respect to separate moieties on (9, 0) metallic
      nanotubes, which suggests that pair formation is not significantly favoured on
      some metallic nanotubes. This result explains the observation of stable isolated
      moieties at room temperature in nanotube samples containing random nanotube
      chiralities. 

PMID- 23974268
TI  - Legacy metals within urban aquatic environments and the challenge they pose to
      rehabilitation.
AB  - Legacy metals, a result of previous environmentally unsound practices, pose a
      challenge to the rehabilitation of urban aquatic ecosystems. The current study
      focuses on a harbor in Vancouver, British Columbia, Canada, where use of
      antifouling paints for hull cleaning occurred for ca. 30 years. Sediment metal
      concentrations were mapped by depth and distance from where hulls were cleaned.
      By relating metal concentrations to the benthic invertebrate community and
      bivalve metal content, results indicate that cleaning activities severely
      impacted sediment quality. However, sewer outfalls, which integrate non-point
      sources of metals to the harbor, also contributed to poor sediment quality and
      high metal concentrations in bivalves. For the aquatic system to recover, non
      point diffuse metal sources must be addressed, regardless of the challenge. 

PMID- 23974269
TI  - Endocarditis caused by Candida dubliniensis.
AB  - Endocarditis caused by Candida dubliniensis is a rare event and limited to few
      case reports. In this report, the authors present a patient with a history of
      intravenous drug use and hepatitis C and endocarditis involving a prosthetic
      aortic valve. Also reviewed are the treatment guidelines for Candida sp.
      endocarditis.

PMID- 23974270
TI  - Reversal of a dabigatran overdose: what are possible options?

PMID- 23974271
TI  - The efficacy of nonestrogenic therapy to hot flashes in cancer patients under
      hormone manipulation therapy: a systematic review and meta-analysis.
AB  - PURPOSE: The incidence of hot flashes under hormone manipulation therapy is so
      high that this symptom caused by sex hormone blocking agents has been bothering
      patients and has a negative impact on their quality of life. Venlafaxine and
      gabapentin are most promising novel nonestrogenic agents to control the symptom.
      We seek to quatitatively summarize the efficacy of these novel agents. PATIENTS
      AND METHODS: We conducted a meta-analysis of randomized controlled studies on the
      efficacy of venlafaxine/gabapentin to hot flashes in cancer patient under hormone
      deprivation therapies. A search for Medline, Embase, Cochrane Central Register of
      Controlled Trials, Ichushi, and Google Scholar yielded 733 citations, which were
      independently assessed by two authors. We estimated overall effect sizes and its
      95 % confidence intervals (CI) for the efficacy of these agents compared with the
      controls with standardized mean difference. RESULTS: A total of 5 studies
      involving 588 cancer patients with hot flashes finally fulfilled the predefined
      inclusion criteria. Overall effect size of the efficacy of venlafaxine/gabapentin
      was -0.630 (95 % CI [-0.801, -0.459]). CONCLUSION: Venlafaxine/gabapentin
      significantly improved hot flashes in cancer patients under hormone manipulation
      therapies.

PMID- 23974272
TI  - Solid predominant histology predicts EGFR tyrosine kinase inhibitor response in
      patients with EGFR mutation-positive lung adenocarcinoma.
AB  - BACKGROUND: The efficacy of epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitors (TKIs) differs in patients with lung adenocarcinoma harboring
      EGFR-activating mutations. Although lung adenocarcinoma with EGFR-activating
      mutations has heterogeneous morphologic features, the predictive role of
      histologic subtype of lung adenocarcinoma with regard to the effectiveness of
      EGFR-TKIs in patients with EGFR-activating mutations has not been well defined.
      METHODS: Among 134 postoperative recurrence patients with lung adenocarcinoma
      harboring EGFR-activating mutation (L858R or exon 19 deletion) treated with EGFR
      TKIs, we retrospectively analyzed 61 patients treated with EGFR-TKIs as first
      line chemotherapy. All the tumors were classified according to the new histologic
      classification proposed by the International Association for the Study of Lung
      Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society
      (ERS) into the following subtypes: lepidic, papillary, acinar, micropapillary, or
      solid predominant subtype. We evaluated the correlation between the histologic
      subtype and the clinical efficacy of EGFR-TKIs. RESULTS: In overall response
      rate, adenocarcinoma with solid predominant subtype is significantly worse than
      with non-solid predominant subtype (61 vs. 88 %, P = 0.03). The median
      progression-free survival (PFS) and overall survival after EGFR-TKI treatment
      were significantly shorter for the patients with solid predominant subtype than
      for those with non-solid predominant subtype (median PFS of 7.7 vs. 13.5 months,
      P = 0.002, and median OS of 21.5 vs. 31.0 months, P = 0.028). CONCLUSIONS: This
      study indicated that among patients with lung adenocarcinoma harboring activating
      EGFR mutations treated with EGFR-TKIs, solid predominant subtype according to
      IASLC/ATS/ERS classification is a response predictor for EGFR-TKI.

PMID- 23974273
TI  - How age of bilingual exposure can change the neural systems for language in the
      developing brain: a functional near infrared spectroscopy investigation of
      syntactic processing in monolingual and bilingual children.
AB  - Is the developing bilingual brain fundamentally similar to the monolingual brain
      (e.g., neural resources supporting language and cognition)? Or, does early-life
      bilingual language experience change the brain? If so, how does age of first
      bilingual exposure impact neural activation for language? We compared how
      typically-developing bilingual and monolingual children (ages 7-10) and adults
      recruit brain areas during sentence processing using functional Near Infrared
      Spectroscopy (fNIRS) brain imaging. Bilingual participants included early-exposed
      (bilingual exposure from birth) and later-exposed individuals (bilingual exposure
      between ages 4-6). Both bilingual children and adults showed greater neural
      activation in left-hemisphere classic language areas, and additionally, right
      hemisphere homologues (Right Superior Temporal Gyrus, Right Inferior Frontal
      Gyrus). However, important differences were observed between early-exposed and
      later-exposed bilinguals in their earliest-exposed language. Early bilingual
      exposure imparts fundamental changes to classic language areas instead of
      alterations to brain regions governing higher cognitive executive functions.
      However, age of first bilingual exposure does matter. Later-exposed bilinguals
      showed greater recruitment of the prefrontal cortex relative to early-exposed
      bilinguals and monolinguals. The findings provide fascinating insight into the
      neural resources that facilitate bilingual language use and are discussed in
      terms of how early-life language experiences can modify the neural systems
      underlying human language processing. 

PMID- 23974276
TI  - Effect of short-term testosterone replacement therapy on heart rate variability
      in men with hypoandrogen-metabolic syndrome.
AB  - INTRODUCTION:  Testosterone deficiency syndrome (TDS) is characterized by
      clinical signs of testosterone deficiency in men with reduced testosterone
      levels. It leads to endothelial dysfunction, which, apart from erectile
      dysfunction, accelerates atherosclerosis progression. OBJECTIVES:  The aim of the
      study was to evaluate the effect of testosterone supplementation in men with
      metabolic syndrome (MS) and TDS on autonomic balance assessed by heart rate
      variability (HRV) in 24-hour Holter monitoring. PATIENTS AND METHODS:  The study
      included 80 men divided into 3 groups: with MS and TDS (MS+TDS+, n = 30), with MS
      and without TDS (MS+TDS-, n = 25), and healthy controls (n = 25). The MS+TDS+
      group received intramuscular testosterone therapy (Omnadren 250) for 9 weeks.
      Holter monitoring was performed in all patients at baseline and at the end of the
      therapy.  RESULTS:  Almost all HRV parameters were significantly lower in the
      MS+TDS+ group compared with controls. Moreover, total power (TP) as well as high-
      and low-frequency domains (HF and LF, respectively) were significantly lower in
      the MS+TDS+ group compared with the MS+TDS- group. There were significant
      differences in the standard deviation (SD) of normal-to-normal (NN) intervals
      (SDNN), SDNN index (SDNNI), and SDANN (SD of the averages of NN intervals in all
      5-minute segments) as well as in ultra-low-frequency (ULF) domain between the
      MS+TDS- group and controls. Testosterone supplementation resulted in a
      statistically significant increase in SDNN, SDANN, TP, LF, ULF, and very-low
      frequency domain. However, the values did not reach those observed in the control
      group. The levels of total and free testosterone were not significantly affected
      by the treatment.  CONCLUSIONS:  A 9-week testosterone supplementation therapy
      improves HRV parameters. Although these parameters did not reach the values
      observed in healthy men, the therapy may reduce cardiovascular risk in men with
      MS and TDS.

PMID- 23974275
TI  - Detection and quantification of chimerism by droplet digital PCR.
AB  - Accurate quantification of chimerism and microchimerism is proving to be
      increasingly valuable for hematopoietic cell transplantation as well as non
      transplant conditions. However, methods that are available to quantify low-level
      chimerism lack accuracy. Therefore, we developed and validated a method for
      quantifying chimerism based on digital PCR technology. We demonstrate accurate
      quantification that far exceeds what is possible with analog qPCR down to 0.01%
      with the potential to go even lower. Also, this method is inherently more
      informative than qPCR. We expect the advantages of digital PCR will make it the
      preferred method for chimerism analysis. 

PMID- 23974274
TI  - Complex chimerism: pregnancy after solid organ transplantation.
AB  - Thousands of women with organ transplantation have undergone successful
      pregnancies, however little is known about how the profound immunologic changes
      associated with pregnancy might influence tolerance or rejection of the
      allograft. Pregnant women with a solid organ transplant are complex chimeras with
      multiple foreign cell populations from the donor organ, fetus, and mother of the
      pregnant woman. We consider the impact of complex chimerism and pregnancy
      associated immunologic changes on tolerance of the allograft both during
      pregnancy and the postpartum period. Mechanisms of allograft tolerance are likely
      dynamic during pregnancy and affected by the influx of fetal microchimeric cells,
      HLA relationships (between the fetus, pregnant woman and/or donor), peripheral T
      cell tolerance to fetal cells, and fetal minor histocompatibility antigens.
      Further research is necessary to understand the complex immunology during
      pregnancy and the postpartum period of women with a solid organ transplant. 

PMID- 23974277
TI  - Non-invasive management of acute recurrent puerperal uterine inversion with Bakri
      postpartum balloon.

PMID- 23974279
TI  - Induction of labor at 41 weeks of pregnancy among primiparas with an unfavorable
      Bishop score.
AB  - OBJECTIVE: To determine the rate and factors associated with the successful
      Induction of Labor (IOL) in nulliparous patients undergoing scheduled IOL at 41
      weeks of gestational age (GA) with an unfavorable cervix. DESIGN: This was a
      retrospective analysis that included nulliparous patients who presented to the
      Labor and Delivery unit at the Bronx Lebanon Hospital Center between 2011 and
      2012 for elective IOL at 41 weeks of GA. The Bishop score was assessed upon
      admission and IOL agents were used in compliance with ACOG guidelines in
      different combinations, based on the obstetrical team preference. SETTING: Labor
      and Delivery Unit of the Bronx Lebanon Hospital. POPULATION: Nulliparous patients
      with 41 weeks of pregnancy for elective induction of labor. SAMPLE: Seventy-six
      patients were included in the study. GA was confirmed using a combination of the
      last menstrual period and a dating sonogram during pregnancy. METHODS: This was a
      retrospective chart review that included nulliparous patients who presented to
      the Labor and Delivery unit at the Bronx Lebanon Hospital Center between October
      2011 and October 2012 for elective IOL at 41 weeks of gestational age with an
      unfavorable cervix defined as a Bishop score of 6 or less. MAIN OUTCOME MEASURES:
      The overall successful rate of IOL in a combination of different maternal factors
      with different agents for induction in nulliparous patients undergoing scheduled
      IOL with an unfavorable Bishop score at 41 weeks of GA was 51.32 %. RESULTS:
      Factors associated with successful IOL were younger age [22.3 years vs. 25.1(p =
      0.015)], lower BMI [25 vs. 28.1(p = 0.46)] and lower maternal weight [64.75 kg
      vs. 74.02 (p = 0.28)]. Maternal height was not a contributing factor; the
      artificial rupture of membranes, epidural anesthesia and the prostaglandins used
      did not contribute. Use of cervical balloon and oxytocin was associated with
      failed IOL. CONCLUSIONS: Patients undergoing IOL at 41 weeks with an unfavorable
      cervix had a successful rate of 51.32 %. Younger maternal age, lower weight, and
      lower BMI were associated with successful IOL.

PMID- 23974278
TI  - Prognostic importance of survivin, Ki-67, and topoisomerase IIalpha in ovarian
      carcinoma.
AB  - PURPOSE: Stage, tumor grade and histological subtype determine the clinical
      behavior in ovarian tumors. Some additional factors are related to tumor cell
      biology and are the useful predictors for identifying the patients with poor
      prognosis. The aim of this study is to evaluate the prognostic significance of
      survivin, Ki-67 and Topoisomerase IIalpha (TOPO IIalpha) in epithelial ovarian
      cancer (EOC). MATERIALS AND METHODS: Seventy-three patients with EOC were
      included in this study. Survivin, Ki-67 and TOPO IIalpha expressions were studied
      by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections.
      Nuclear staining for all antibodies was scored on a three-tiered system and more
      than 10 % staining was accepted as expression. The relationship between the
      expressions of survivin, Ki-67, TOPO IIalpha and clinicopathological parameters
      including age, stage, grade, platinum resistance and survival was evaluated.
      RESULTS: Survivin, Ki-67 and TOPO IIalpha expressions were found in 20, 82 and 86
      % of the tumors, respectively. Ki-67 and TOPO IIalpha expressions were found to
      be related to poor overall survival (p = 0.005, 0.004, respectively), while
      survivin expression was not associated with overall survival. There was no
      association between TOPO IIalpha and Ki-67 expressions and histological subtype,
      stage or grade. However, we found an important relationship between TOPO IIalpha
      expression and platinum resistance (p = 0.044). Platinum resistance was found to
      be an independent prognostic factor in EOC. CONCLUSION: Ki-67 and TOPO IIalpha
      expressions were found to be related to poor overall survival, and TOPO IIalpha
      expression was found to be associated with platinum resistance.

PMID- 23974280
TI  - The four steps in the prevention of human papillomavirus-associated neoplasia:
      considerations for preventive measures, screening, disease impact, and potential
      overtreatments in HPV-related pathology.
AB  - There is no cure currently available for HPV infections, although ablative and
      excisional treatments of some dysplasias often result in a clinical and
      virological cure. Effective control measures of HPV-associated cancers rely on
      the prevention at four different levels. Apart from sexual abstinence, primary
      prevention is realized through vaccines targeting the most frequent HPV types:
      negative attitudes towards HPV vaccination and high costs are the main obstacles.
      The aim of secondary prevention is to detect precancerous changes before they
      develop into invasive cancer, while tertiary prevention involves actual treatment
      of high-grade lesions: in many countries routine screening with cytology is being
      challenged with HPV DNA testing. Quaternary prevention comprehends those actions
      adopted to mitigate or avoid unnecessary or excessive medical interventions, and
      may well be addressed in avoiding treatments for low-grade intraepithelial
      neoplasia. Though some gynecologists commonly recommend treatment for low-grade
      disease and women tend to prefer active management if not properly informed,
      harms arising from unnecessary treatments, increased costs, work overload for
      second-level health services, and induced psychosocial distress are causing on
      going problems. Prevention efforts of genital HPV-associated cancers should
      concentrate in: (1) enhancing primary prevention through vaccination of all
      eligible subjects, (2) achieving high levels of adherence to routine screening
      programs, (3) treating precancerous lesions, and (4) monitoring current
      guidelines recommendations to avoid overtreatments. Novel research projects
      should be designed to study the delicate mechanisms of immune response to HPV. 

PMID- 23974281
TI  - Polymorphisms in the promoter region of estrogen receptor beta gene in
      endometrial cancer.
AB  - INTRODUCTION: The development of endometrial cancer is known to be affected by
      estrogens. Thus, genetic variations like single nucleotide polymorphisms (SNPs)
      in genes involved in estrogen biosynthesis, metabolism, and signal transduction
      might affect risk for endometrial cancer. In this study, we tested the hypothesis
      that polymorphisms in the promoter of ESR2 gene may be associated with
      susceptibility to this disease. METHODS: We compared the frequency of three SNPs
      in the promoter region of ESR2 gene (rs2987983, rs3020450, and rs3020449) in 135
      women with endometrial cancer and 135 healthy women serving as controls by means
      of allele-specific tetra-primer PCR. RESULTS: Regarding allele frequency, allele
      positivity or genotype frequencies of these SNPs we did not observe any
      significant difference between healthy women and women with endometrial cancer.
      CONCLUSION: Our data clearly suggest that the tested SNPs in the promotor region
      of human ESR2 gene are not associated with the development of endometrial cancer.

PMID- 23974282
TI  - High charge-carrier mobility enables exploitation of carrier multiplication in
      quantum-dot films.
AB  - Carrier multiplication, the generation of multiple electron-hole pairs by a
      single photon, is of great interest for solar cells as it may enhance their
      photocurrent. This process has been shown to occur efficiently in colloidal
      quantum dots, however, harvesting of the generated multiple charges has proved
      difficult. Here we show that by tuning the charge-carrier mobility in quantum-dot
      films, carrier multiplication can be optimized and may show an efficiency as high
      as in colloidal dispersion. Our results are explained quantitatively by the
      competition between dissociation of multiple electron-hole pairs and Auger
      recombination. Above a mobility of ~1 cm(2) V(-1) s(-1), all charges escape Auger
      recombination and are quantitatively converted to free charges, offering the
      prospect of cheap quantum-dot solar cells with efficiencies in excess of the
      Shockley-Queisser limit. In addition, we show that the threshold energy for
      carrier multiplication is reduced to twice the band gap of the quantum dots.

PMID- 23974283
TI  - The time course of eye movements during action observation reflects sequence
      learning.
AB  - When we observe object-directed actions such as grasping, we make predictive eye
      movements. However, eye movements are reactive when observing similar actions
      without objects. This reactivity may reflect a lack of attribution of intention
      to observed actors when they perform actions without 'goals'. Alternatively, it
      may simply signal that there is no cue present that has been predictive of the
      subsequent trajectory in the observer's experience. To test this hypothesis, the
      present study investigated how the time course of eye movements changes as a
      function of visual experience of predictable, but arbitrary, actions without
      objects. Participants observed a point-light display of a model performing
      sequential finger actions in a serial reaction time task. Eye movements became
      less reactive across blocks. In addition, participants who exhibited more
      predictive eye movements subsequently demonstrated greater learning when required
      either to execute, or to recognize, the sequence. No measures were influenced by
      whether participants had been instructed that the observed movements were human
      or lever generated. The present data indicate that eye movements when observing
      actions without objects reflect the extent to which the trajectory can be
      predicted through experience. The findings are discussed with reference to the
      implications for the mechanisms supporting perception of actions both with and
      without objects as well as those mediating inanimate object processing. 

PMID- 23974287
TI  - The man behind the journal: Editors-in-Chief of the Polish Archives of Internal
      Medicine (1923-2013).

PMID- 23974286
TI  - Lipids of Candida albicans and their role in multidrug resistance.
AB  - Over the years, lipids of non-pathogenic yeast such as Saccharomyces cerevisiae
      have been characterized to some details; however, a comparable situation does not
      exist for the human pathogenic fungi. This review is an attempt to bring in
      recent advances made in lipid research by employing high throughput lipidomic
      methods in terms of lipid analysis of pathogenic yeasts. Several pathogenic fungi
      exhibit multidrug resistance (MDR) which they acquire during the course of a
      treatment. Among the several causal factors, lipids by far have emerged as one of
      the critical contributors in the MDR acquisition in human pathogenic Candida. In
      this article, we have particularly focused on the role of lipids involved in
      cross talks between different cellular circuits that impact the acquisition of
      MDR in Candida. 

PMID- 23974288
TI  - Distinguished Polish internists: Witold E. Orlowski and Msciwoj M. Semerau
      Siemianowski.

PMID- 23974289
TI  - 2012 impact factor of the Pol Arch Med Wewn: new challenges and hopes.

PMID- 23974290
TI  - Guidelines serving to guide practicing physicians: comment on the paper by
      Tomasik et al.

PMID- 23974291
TI  - Giant left atrial myxoma as a cause of recurrent cerebral emboli.

PMID- 23974285
TI  - Endocytic regulation of alkali metal transport proteins in mammals, yeast and
      plants.
AB  - The relative concentrations of ions and solutes inside cells are actively
      maintained by several classes of transport proteins, in many cases against their
      concentration gradient. These transport processes, which consume a large portion
      of cellular energy, must be constantly regulated. Many structurally distinct
      families of channels, carriers, and pumps have been characterized in considerable
      detail during the past decades and defects in the function of some of these
      proteins have been linked to a growing list of human diseases. The dynamic
      regulation of the transport proteins present at the cell surface is vital for
      both normal cellular function and for the successful adaptation to changing
      environments. The composition of proteins present at the cell surface is
      controlled on both the transcriptional and post-translational level. Post
      translational regulation involves highly conserved mechanisms of phosphorylation-
      and ubiquitylation-dependent signal transduction routes used to modify the cohort
      of receptors and transport proteins present under any given circumstances. In
      this review, we will summarize what is currently known about one facet of this
      regulatory process: the endocytic regulation of alkali metal transport proteins.
      The physiological relevance, major contributors, parallels and missing pieces of
      the puzzle in mammals, yeast and plants will be discussed. 

PMID- 23974292
TI  - Oral leukoplakia in a diabetic patient treated with tretinoin.

PMID- 23974293
TI  - New minimally invasive therapeutic method in chronic back pain.

PMID- 23974294
TI  - Altered metabolism of prostaglandin E2 in asthma patients with aspirin
      hypersensitivity.

PMID- 23974295
TI  - A class of high performance metal-free oxygen reduction electrocatalysts based on
      cheap carbon blacks.
AB  - For the goal of practical industrial development of fuel cells, cheap,
      sustainable and high performance electrocatalysts for oxygen reduction reactions
      (ORR) which rival those based on platinum (Pt) and other rare materials are
      highly desirable. In this work, we report a class of cheap and high-performance
      metal-free oxygen reduction electrocatalysts obtained by co-doping carbon blacks
      with nitrogen and fluorine (CB-NF).The CB-NF electrocatalysts are highly active
      and exhibit long-term operation stability and tolerance to poisons during oxygen
      reduction process in alkaline medium. The alkaline direct methanol fuel cell with
      the best CB-NF as cathode (3 mg/cm(2)) outperforms the one with commercial
      platinum-based cathode (3 mg Pt/cm(2)). To the best of our knowledge, these are
      among the most efficient non-Pt based electrocatalysts. Since carbon blacks are
      10,000 times cheaper than Pt, these CB-NF electrocatalysts possess the best
      price/performance ratio for ORR, and are the most promising alternatives to Pt
      based ones to date. 

PMID- 23974296
TI  - Stepwise oligomerization of murine amylin and assembly of amyloid fibrils.
AB  - Amylin is a pancreatic hormone co-secreted with insulin. Human amylin has been
      shown to form dimers and exhibit high propensity for amyloid fibril formation. We
      observed the ability of the water-soluble murine amylin to aggregate in water
      resulting in an insoluble material with Thioflavin T binding properties. Infrared
      spectroscopy analysis revealed beta-sheet components in the aggregated murine
      amylin. Morphological analysis by transmission electron microscopy and atomic
      force microscopy provided access to the fibril nature of the murine amylin
      aggregate which is similar to amyloid fibrils from human amylin. X-ray
      diffraction of the murine amylin fibrils showed peaks at 4.7A and 10A, a
      fingerprint for amyloid fibrils. Electron spray ionization-ion mobility
      spectroscopy-mass spectrometry (ESI-IMS-MS) analysis and crosslinking assays
      revealed self-association intermediates of murine amylin into high order
      oligomeric assemblies. These data demonstrate the stepwise association mechanism
      of murine amylin into stable oligomers, which ultimately converges to its
      organization into amyloid fibrils. 

PMID- 23974297
TI  - The effect of high-fat diet on the composition of the gut microbiota in cloned
      and non-cloned pigs of lean and obese phenotype.
AB  - The aim of this study was to investigate the effect of high-far-high-energy diet
      on cloned and non-cloned domestic pigs of both lean and obese phenotype and to
      evaluate if the lean cloned pigs had a lower inter-individual variation as
      compared with non-cloned pigs. The microbiota of colon and terminal ileum was
      investigated in cloned and non-cloned pigs that received a high-far-high-energy
      diet with either restricted or ad libitum access to feed, resulting in lean and
      obese phenotypes, respectively. The fecal microbiota of lean pigs was
      investigated by terminal restriction fragment length polymorphism (T-RFLP). The
      intestinal microbiota of lean and obese cloned and non-cloned pigs was analyzed
      by quantitative real time PCR and a novel high-throughput qPCR platform
      (Fluidigm). Principal component analysis (PCA) of the T-RFLP profiles revealed
      that lean cloned and non-cloned pigs had a different overall composition of their
      gut microbiota. The colon of lean cloned pigs contained relatively more bacteria
      belonging to the phylum Firmicutes and less from the phylum Bacteroidetes than
      obese cloned pigs as estimated by qPCR. Fluidigm qPCR results revealed
      differences in specific bacterial groups in the gut microbiota of both lean and
      obese pigs. Our results suggest that high-far-high-energy diet is associated with
      changes in the gut microbiota even in the absence of obesity. Overall, the cloned
      pigs had a different gut microbiota from that of non-cloned pigs. To our
      knowledge this is the first study to investigate the gut microbiota of cloned
      domestic pigs of lean and obese phenotype. 

PMID- 23974299
TI  - Arterial distensibility in patients with ruptured and unruptured intracranial
      aneurysms: is it a predisposing factor for rupture risk?
AB  - BACKGROUND: A risk factor assessment that reliably predicts whether patients are
      predisposed to intracranial aneurysm (IA) rupture has yet to be formulated. As
      such, the clinical management of unruptured IA remains unclear. Our aim was to
      determine whether impaired arterial distensibility and hypertrophic remodeling
      might be indicators of risk for IA rupture. MATERIAL/METHODS: The study
      population (n=49) was selected from consecutive admissions for either unruptured
      IA (n=23) or ruptured IA (n=26) from January to December 2010. Hemodynamic
      measures were taken from every patient, including systolic and diastolic blood
      pressure using a sphygmomanometer. Unruptured IA and ruptured IA characteristics,
      including aneurysmal shape, size, angle, aspect ratio, and bottleneck factor,
      were measured and calculated from transverse brain CT angiography images. With
      ultrasound, the right common carotid artery intima-media thickness was measured,
      as well as the lumen diameter during systole and diastole. Arterial wall strain,
      distensibility, stiffness index, and elastic modulus were calculated and compared
      between patients with unruptured IAs and ruptured IAs. A p-value less than 0.05
      was considered statistically significant. RESULTS: General demographic data did
      not differ between patients with unruptured IAs and ruptured IAs. Greater mean
      intima-media thickness (p=0.013), mean stiffness index (p=0.044), and mean
      elastic modulus (p=0.026) were observed for patients with ruptured IAs. Moreover,
      mean strain (p=0.013) and mean distensibility (p=0.024) were decreased in
      patients with ruptured IAs. CONCLUSIONS: Patients with ruptured IAs demonstrated
      decreased arterial distensibility and increased intima-media thickness at the
      level of the carotid arteries. By measuring these parameters via ultrasound, it
      may be possible to predict whether patients with existing IAs might rupture and
      hemorrhage into the subarachnoid space.

PMID- 23974298
TI  - CAS directly interacts with vinculin to control mechanosensing and focal adhesion
      dynamics.
AB  - Focal adhesions are cellular structures through which both mechanical forces and
      regulatory signals are transmitted. Two focal adhesion-associated proteins, Crk
      associated substrate (CAS) and vinculin, were both independently shown to be
      crucial for the ability of cells to transmit mechanical forces and to regulate
      cytoskeletal tension. Here, we identify a novel, direct binding interaction
      between CAS and vinculin. This interaction is mediated by the CAS SRC homology 3
      domain and a proline-rich sequence in the hinge region of vinculin. We show that
      CAS localization in focal adhesions is partially dependent on vinculin, and that
      CAS-vinculin coupling is required for stretch-induced activation of CAS at the
      Y410 phosphorylation site. Moreover, CAS-vinculin binding significantly affects
      the dynamics of CAS and vinculin within focal adhesions as well as the size of
      focal adhesions. Finally, disruption of CAS binding to vinculin reduces cell
      stiffness and traction force generation. Taken together, these findings strongly
      implicate a crucial role of CAS-vinculin interaction in mechanosensing and focal
      adhesion dynamics. 

PMID- 23974301
TI  - Reliable set-up for in-loop 11C-carboxylations using Grignard reactions for the
      preparation of [carbonyl-11C]WAY-100635 and [11C]-(+)-PHNO.
AB  - Aim of this work was the implementation of a generalized in-loop synthesis for
      (11)C-carboxylations and subsequent (11)C-acylations on the TRACERlab FxC Pro
      platform. The set-up was tested using [carbonyl-(11)C]WAY-100635 and, for the
      first time, [(11)C]-(+)-PHNO. Its general applicability could be demonstrated and
      both [carbonyl-(11)C]WAY-100635 and [(11)C]-(+)-PHNO were prepared with high
      reliability and satisfying outcome.

PMID- 23974300
TI  - Platelet size and density affect shear-induced thrombus formation in tortuous
      arterioles.
AB  - Thrombosis accounts for 80% of deaths in patients with diabetes mellitus.
      Diabetic patients demonstrate tortuous microvessels and larger than normal
      platelets. Large platelets are associated with increased platelet activation and
      thrombosis, but the physical effects of large platelets in the microscale
      processes of thrombus formation are not clear. Therefore, the objective of this
      study was to determine the physical effects of mean platelet volume (MPV), mean
      platelet density (MPD) and vessel tortuosity on platelet activation and thrombus
      formation in tortuous arterioles. A computational model of the transport, shear
      induced activation, collision, adhesion and aggregation of individual platelets
      was used to simulate platelet interactions and thrombus formation in tortuous
      arterioles. Our results showed that an increase in MPV resulted in a larger
      number of activated platelets, though MPD and level of tortuosity made little
      difference on platelet activation. Platelets with normal MPD yielded the lowest
      amount of mural thrombus. With platelets of normal MPD, the amount of mural
      thrombus decreased with increasing level of tortuosity but did not have a simple
      monotonic relationship with MPV. The physical mechanisms associated with MPV, MPD
      and arteriole tortuosity play important roles in platelet activation and thrombus
      formation. 

PMID- 23974302
TI  - Fully automated synthesis of 11C-acetate as tumor PET tracer by simple modified
      solid-phase extraction purification.
AB  - INTRODUCTION: Automated synthesis of (11)C-acetate ((11)C-AC) as the most
      commonly used radioactive fatty acid tracer is performed by a simple, rapid, and
      modified solid-phase extraction (SPE) purification. METHODS: Automated synthesis
      of (11)C-AC was implemented by carboxylation reaction of MeMgBr on a polyethylene
      Teflon loop ring with (11)C-CO2, followed by acidic hydrolysis with acid and SCX
      cartridge, and purification on SCX, AG11A8 and C18 SPE cartridges using a
      commercially available (11)C-tracer synthesizer. Quality control test and animals
      positron emission tomography (PET) imaging were also carried out. RESULTS: A high
      and reproducible decay-uncorrected radiochemical yield of (41.0 +/- 4.6)% (n=10)
      was obtained from (11)C-CO2 within the whole synthesis time about 8 min. The
      radiochemical purity of (11)C-AC was over 95% by high-performance liquid
      chromatography (HPLC) analysis. Quality control test and PET imaging showed that
      (11)C-AC injection produced by the simple SPE procedure was safe and efficient,
      and was in agreement with the current Chinese radiopharmaceutical quality control
      guidelines. CONCLUSION: The novel, simple, and rapid method is readily adapted to
      the fully automated synthesis of (11)C-AC on several existing commercial
      synthesis module. The method can be used routinely to produce (11)C-AC for
      preclinical and clinical studies with PET imaging.

PMID- 23974303
TI  - Activation cross-sections of deuteron induced reaction of natural Ni up to 40
      MeV.
AB  - Production cross-sections of (nat)Ni(d,x)(56,57)Ni, (55,56,57,58)Co, (52,54)Mn,
      and (51)Cr nuclear reactions were measured up to 40 MeV by using the stacked foil
      technique. The results were compared with the literature values, TALYS 1.4 and
      TENDL-2012. Spline fits were made on the selected data, from which physical
      yields were calculated and compared with the literature and our directly measured
      thick target yield values. (nat)Ni(d,x)(56,57,58)Co reactions were analyzed for
      beam monitoring and thin layer activation (TLA). Rate of production of (55)Co was
      compared between proton and deuteron induced reactions.

PMID- 23974304
TI  - Radiosynthesis and in vivo evaluation of a 18F-labelled styryl-benzoxazole
      derivative for beta-amyloid targeting.
AB  - The formation of beta-amyloid deposits is considered a histopathological feature
      of Alzheimer's disease (AD). In vivo molecular imaging by means of amyloid-avid
      radiotracers will allow for an early and conclusive diagnostic of AD. Herein, we
      describe the radiosynthesis of the radiofluorinated styryl benzoxazole derivative
      [18F]-[2-[N-methyl-N-(2'-fluoroethyl)-4'-aminostyryl]benzoxazole] ([18F]-1) and
      its pre-clinical evaluation, including metabolic and biodistribution studies in
      male Wistar rats. The in vivo biological evaluation of [18F]-1 showed that this
      new radiotracer has a moderate brain uptake with a slow brain washout and a poor
      in vivo stability.

PMID- 23974305
TI  - Uranium deposition in bones of Wistar rats associated with skeleton development.
AB  - Sixty female Wistar rats were submitted to a daily intake of ration doped with
      uranium from weaning to adulthood. Uranium in bone was quantified by the SSNTD
      (solid state nuclear track detection) technique, and bone mineral density (BMD)
      analysis performed. Uranium concentration as a function of age exhibited a sharp
      rise during the first week of the experiment and a drastic drop of 70% in the
      following weeks. Data interpretation indicates that uranium mimics calcium.
      Results from BMD suggest that radiation emitted by the incorporated Uranium could
      induce death of bone cells. 

PMID- 23974306
TI  - New filter for iodine applied in nuclear medicine services.
AB  - In Nuclear Medicine, radioiodine, in various chemical forms, is a key tracer used
      in diagnostic practices and/or therapy. Medical professionals may incorporate
      radioactive iodine during the preparation of the dose to be administered to the
      patient. In radioactive iodine therapy doses ranging from 3.7 to 7.4 GBq per
      patient are employed. Thus, aiming at reducing the risk of occupational
      contamination, we developed a low cost filter to be installed at the exit of the
      exhaust system (where doses of radioiodine are handled within fume hoods, and new
      filters will be installed at their exit), using domestic technology. The
      effectiveness of radioactive iodine retention by silver impregnated silica [10%]
      crystals and natural activated carbon was verified using radiotracer techniques.
      The results showed that natural activated carbon and silver impregnated silica
      are effective for I2 capture with large or small amounts of substrate but the use
      of activated carbon is restricted due to its low flash point (423 K). Besides,
      when poisoned by organic solvents, this flash point may become lower, causing
      explosions if absorbing large amounts of nitrates. To hold the CH3I gas, it was
      necessary to use natural activated carbon since it was not absorbed by SiO2+Ag
      crystals. We concluded that, for an exhaust flow range of (145 +/- 2)m(3)/h, a
      double stage filter using SiO2+Ag in the first stage and natural activated carbon
      in the second stage is sufficient to meet radiological safety requirements.

PMID- 23974307
TI  - A simple theoretical model for 63Ni betavoltaic battery.
AB  - A numerical simulation of the energy deposition distribution in semiconductors is
      performed for 63Ni beta particles. Results show that the energy deposition
      distribution exhibits an approximate exponential decay law. A simple theoretical
      model is developed for 63Ni betavoltaic battery based on the distribution
      characteristics. The correctness of the model is validated by two literature
      experiments. Results show that the theoretical short-circuit current agrees well
      with the experimental results, and the open-circuit voltage deviates from the
      experimental results in terms of the influence of the PN junction defects and the
      simplification of the source. The theoretical model can be applied to 63Ni and
      147Pm betavoltaic batteries.

PMID- 23974309
TI  - Topical cidofovir for treatment of resistant viral infections.
AB  - Cidofovir is a broad-spectrum antiviral agent with activity against several DNA
      viruses. An application to approve the use of topical cidofovir for acyclovir
      resistant herpes virus infection was denied by the US Food and Drug
      Administration owing to the lack of phase III clinicla trial data. The
      manufacturer stated that, as of 1997, no further controlled studies were planned
      or in progress to evaluate topical cidofovir in herpes simplex infections. It is
      unknown whether there are plans to conduct controlled studies of topical
      cidofovir for HPV or MVC infections. However, numerous case reports and published
      studies describe successful use of topical cidofovir to treat resistant and
      severe forms of viral infections such as molluscum contagiosum, condylomata
      acuminata, verruca vulgaris, herpes simplex virus infection, genital warts, and
      ginigval infection with human papillomavirus. Because of the mutagenic properties
      of cidofovir, compounding the preparation is considered hazardous. Since most
      retail pharmacies do no have the safety equipment necessary to compound hazardous
      preparations, a compounding pharmacist can play a vital role in preparing topical
      cidofovir cream or gel. 

PMID- 23974310
TI  - Mesotherapy: cosmetic applications.
AB  - Mesotherapy, which has been compared to the anti-wrinkle injection Botox, has
      only recently become popular in the United States for providing body contouring
      and spot weight loss. Most adverse reactions associated with mesotherapy are mild
      and transient, and supporters of the procedure consider it a safer alternative to
      liposuction. Mainly owing to the absence of safety and efficacy data pertaining
      to mesotherapy, liposuction is currently the only method for fat removal that is
      endorsed by the American Society of Plastic Surgeons . Although mesotherapy has
      been used as a treatment for pain syndromes, arthritis, and many other disorders,
      this article focuses on its cosmetic applications. 

PMID- 23974311
TI  - Dermatological effects from years in the sun: compounding opportunities.
AB  - Sun worship has existed for thousands of years and the popularity of sunbathing
      and tanning salons proves that it still exists today. Overexposure to the
      ultraviolet rays of the sun and tanning beds is a major cause of skin damage and
      the main cause of precancerous and cancerous skin lesions. Regardless of the many
      warnings about the dangers of sun exposure and the many sunscreen products
      available, a significant number of people develop these lesions. The most common
      sun-induced pre-cancerous lesion is solar keratosis, or actinic keratosis. Unless
      detected and treated, actinic keratosis can progress to skin cancer. The three
      main types of skin cancer are basal cell carcinoma, squamous cell carcinoma, and
      melanoma. All can be cured if caught early and treated promptly. A number of
      treatment options are available for skin cancers, including topical preparations,
      systemic chemotherapy, photodynamic therapy, and surgery. The best treatment
      option depends on the type and location of lesion, the stage of the lesion, and
      the needs of the individual patient. 

PMID- 23974312
TI  - Migraine: a general approach to prevention and treatment.
AB  - Migraines occasionally are a symptom of another serious underlying health
      condition. Therefore, it is important for pharmacists to be familiar with the
      diagnostic criteria of migraine so that they can recognize which patients warrant
      a referral to a healthcare provider for further evaluation. Criteria for the
      diagnosis of migraines have been established by the International Headache
      Society. To assist migraine sufferers in their efforts to find relief from the
      pain and reduce the occurrence of migraines, it is important that compounding
      pharmacists be aware of the clinical features of migraine such as the four
      phases, the pathophysiology of migraines, the drug classes commonly used in the
      treatment of migraines, the variety of therapeutic approaches, and treatment
      options that may be offered by compounding pharmacists. 

PMID- 23974313
TI  - Case report: treatment of migraines with compounded piroxicam mini-troches.

PMID- 23974314
TI  - University of north Carolina at chapel hill school of pharmacy pharmaceutical
      care laboratories: compounding laboratory curriculum and renovation.
AB  - As part of a concerted effort to update its curriculum and facilities, the
      University of North Carolina at Chapel Hill School of Pharmacy developed a new
      series of laboratory courses that would provide students with better
      opportunities to develop skills and apply them to the modern pharmacy practice of
      pharmaceutical care. Curriculum revisions involved changing the compounding
      laboratory sequence, upgrading the video library, and tying its website to its
      training materials; the compounding laboratory facility was renovated to support
      the demands of the new curriculum. The overall goals of the renovation were to
      (1)increase the number of workstations in the facility, and (2)increase the ease
      with which students could retrieve materials necessary for laboratory projects.
      The renovation schedule was planned so classes were not interrupted. 

PMID- 23974315
TI  - Education, training, and evaluation of hospital compounding personnel.
AB  - Many practicing pharmacists who graduated in the past 20 years have little or no
      compounding education, training, or experience. With the change to the entry
      level PharmD degree now underway in schools of pharmacy, the primary emphasis is
      on clinical practice instead of traditional pharmacy practice. Little or no
      compounding education is offered or required, even though demand for pharmacy
      compounding is steadily increasing. Since compounding is a specialized division
      of the hospital pharmacy department, the compounding staff is held to a higher in
      house standard than the rest of the pharmacy department. According to the United
      States Pharmacopeia Chapter 795, any pharmacist or licensed healthcare
      professional who is responsible for preparing compounds is a "compounder." This
      definition includes compounding pharmacy technicians. Although compounding has
      always been part of hospital pharmacy practice, few hospital pharmacies have
      dedicated laboratories or staff for the specialized tasks of nonsterile
      compounding, high-risk sterile compounding, or unit-dose packaging. Since both
      the American Society of Health-System Pharmacists and the Joint Commission on
      Accreditation of Healthcare Organizations mandate that hospital personnel be
      properly educated and trained according to applicable legal and regulatory
      requirements and oranizational policy in order to fulfill their assigned tasks
      and responsibilities, the education, training, and evaluation of hospital
      compounding personnel is crucial. 

PMID- 23974316
TI  - Medline: a valuable research tool for the compounding pharmacist.
AB  - Compounding pharmacists often find themselves on the cutting edge of medical
      treatment. Prescribers and patients look to compounders for ideas on novel
      treatments or for more information on standard treatments. Even with the vast
      supply of information available on the Internet, finding reliable data from
      trustworhty websites has become increasingly difficult. All too often, an
      Internet search on a specific medical topic may turn up no dependable material.
      For complete, science based information about medical topics, the National
      Library of Medicine's database of medical literature, MEDLINE, is an essential
      tool for the compounding pharmacist. 

PMID- 23974317
TI  - Quality-control analytical methods: sterility failure investigations.
AB  - Sterility testing is an important step in verifying that the aseptic process has
      rendered a preparation sterile. Ensuring sterility involves the oversight and
      control of many factors, including compounding personnel, pharmacy environment,
      equipment and materials used in the compounding of sterile preparations, and
      compounding and aseptic methods. A pharmacy should have a standard operating
      procedure in place for investigating sterility failures, and an important focus
      in the procedure should be good documentation. Routine evaluations of a
      pharmacy's compounding practices should be considered even though such
      evaluations may present a challenge to the pharmacy's quality control system.
      Proper training and encouragement of staff to present possible sterility problems
      could make the difference in avoiding compounding failures. 

PMID- 23974318
TI  - Basics of compounding for hazardous drugs, part 1: an introduction.
AB  - National Institute of Occupational Safety and Health Publication No.2004-165,
      Preventing Occupational Exposure to Antineoplastic and Other Hazarous Drugs in
      Health Care Settings, was published in 2004 to increase the awareness of
      healthcare workers and other professionals about the health risks of working with
      hazardous drugs and to provide measures for protecting their health. The health
      risks to emplyees who prepare or administer hazardous drugs in the workplace is
      influenced by many factors, and each compounding facility is responsible for
      developing its own list of hazardous drugs and for creating standard operating
      procedures to reduce risks as much as possible for employees. To provide
      employees with the greatest protection, employers should (1)implement necessary
      administrative and engineering controls, and (2)assure that the workers use sound
      procedures and proper protective equipment for handling hazardous drugs. 

PMID- 23974319
TI  - In vitro transdermal diffusion of zileuton from a topical gel.
AB  - Zileuton, a leukotriene inhibitor used to treat asthma, is usually administered
      via the oral route. A transdermal drug delivery system for zileuton was developed
      for this study. A vertical diffusion cell and freshly harvested human skin were
      used to test the system. Thirteen percent (3.3mg) of the drug was delivered into
      the dermis within 24 hours, and 13.6% (3.3 mg) of the drug was delivered through
      the epidermis into the receiving chamber of the diffusion cell within 24 hours. A
      specially constructed transdermal zileuton gel delivered 13.1% (3.3 mg) of the
      drug through the epidermis into the receiving chamber within 24 hours. These
      results are predictive of the successful use of zileuton as a transdermal gel in
      human subjects. 

PMID- 23974320
TI  - Temozolomide stability in extemporaneously compounded oral suspensions.
AB  - Temozolomide, commercially available in capsules, is an oral alkylating agent
      used to treat brain tumors. The purpose of this study was to determine the
      pharmaceutical acceptability and chemical stability of temozolomide in two
      extemporaneously compounded suspension formulations prepared from the capsules.
      The temozolomide oral suspensions were prepared from 100-mg commercial capsules
      yielding a nominal temozolomide concentration of 10 mg/mL. The suspension
      vehicles selected for testing were an equal parts mixture of Ora-Plus and Ora
      Sweet and an equal parts mixture of Ora-Plus and Ora-Sweet SF. The suspensions
      were packaged in amber plastic screw-cap prescription bottles, which were stored
      at 23 deg C for 21 days or 4 deg C for 60 days. Stability-indicating high
      performance liquid chromatographic analysis revealed that the temozolomide
      concentration in both suspension vehicle combinations exhibited little or no loss
      for 60 days at 4 deg C. At 23 deg C, temozolomide losses were somewhat greater.
      In the Ora-Sweet formulation, the loss was 6% at 7 days; in the Ora-Sweet SF
      formulation, losses were about 8% at 14 days and 10% to 11% at 21 days.
      Temozolomide extemporaneously prepared as oral suspensions from capsules in equal
      parts mixtures of Ora-Plus suspension vehicle with Ora-Sweet and with ora-Sweet
      SF syrups with added povidine k-30 and acidified with citric acid were
      pharmaceutically acceptable and chemically stable for at least 60 days at 4 deg
      C. Refrigerated storage is recommended. The suspensions should not be stored at
      room temperature longer than 1 week if Ora-Sweet is used or longer than 2 weeks
      if Ora-Sweet SF is used. 

PMID- 23974322
TI  - Breed-linked polymorphisms of porcine toll-like receptor 2 (TLR2) and TLR4 and
      the primary investigation on their relationship with prevention against
      Mycoplasma pneumoniae and bacterial LPS challenge.
AB  - Toll-like receptors (TLRs) play a crucial role in innate immunity, serving as
      pattern-recognition receptors and the first barrier in host defense against
      microbial infections. Genetic variations of TLR2 and TLR4 are closely associated
      with a variety of infectious diseases, particularly lung diseases. In this study,
      we detected six and four single nucleotide polymorphisms (SNPs) in the coding
      sequences of porcine TLR2 and TLR4 genes, respectively. Only SNP 1027C>A of TLR4
      was shown to be markedly biased in Western and Oriental pig populations. Hence,
      the susceptibility of pigs with different genotype at position 1027C>A to
      Mycoplasma hyopneumoniae (Mhp) infection was investigated, and changes to the
      expression of TLR2, TLR4, TNF-alpha and IL-1beta were monitored. The results
      showed that there was no significant difference in susceptibility to Mhp
      infection between AA and CC individuals despite expression levels for all
      detected genes of the challenge groups being significantly higher than the
      corresponding control groups. Furthermore, porcine alveolar macrophages of
      different genotype were collected and stimulated by lipopolysaccharide. We found
      that the expression of TLR2, TLR4, TNF-alpha and IL-1beta genes were enhanced to
      different levels by lipopolysaccharide stimulation. TLR2 and TLR4 gene
      expressions and their rates of increase of 1027CC pigs were significantly higher
      than for 1027AC pigs (P < 0.01), while TNF-alpha and IL-1beta expressions were
      significantly lower than for 1027AC pigs (P < 0.01). We predict that allele C at
      position 1027 of the TLR4 gene contributes to the pig's immune response to gram
      negative bacterial infections. 

PMID- 23974321
TI  - Killer cell immunoglobulin-like receptor (KIR) genes and their HLA-C ligands in a
      Ugandan population.
AB  - Killer cell immunoglobulin-like receptor (KIR) genes are expressed by natural
      killer cells and encoded by a family of genes exhibiting considerable haplotypic
      and allelic variation. HLA-C molecules, the dominant ligands for KIR, are present
      in all individuals and are discriminated by two KIR epitopes, C1 and C2. We
      studied the frequencies of KIR genes and HLA-C1 and C2 groups in a large cohort
      (n = 492) from Kampala, Uganda, East Africa and compared our findings with
      published data from other populations in sub-Saharan Africa (SSA) and several
      European populations. We find considerably more KIR diversity and weaker linkage
      disequilibrium in SSA compared to the European populations and describe several
      novel KIR genotypes. C1 and C2 frequencies were similar to other SSA populations
      with a higher frequency of the C2 epitope (54.9 %) compared to Europe (average
      39.7 %). Analysis of this large cohort from Uganda in the context of other
      African populations reveals variations in KIR and HLA-C1 and C2 that are
      consistent with migrations within Africa and potential selection pressures on
      these genes. Our results will help understand how KIR/HLA-C interactions
      contribute to resistance to pathogens and reproductive success.

PMID- 23974323
TI  - Sequencing of modern Lepus VDJ genes shows that the usage of VHn genes has been
      retained in both Oryctolagus and Lepus that diverged 12 million years ago.
AB  - Among mammals, the European rabbit (Oryctolagus cuniculus) has a unique mechanism
      of generating the primary antibody repertoire. Despite having over 200 VH genes,
      the VH1 gene, the most D-proximal VH gene, is used in 80-90 % of VDJ
      rearrangements, while the remaining 10-20 % is encoded by the VHn genes that map
      at least 100 Kb upstream of VH1. The maintenance of the VHn genes usage in low
      frequency in VDJ rearrangements has been suggested to represent a relic of an
      ancestral immunologic response to pathogens. To address this question, we
      sequenced VDJ genes for another leporid, genus Lepus, which separated from
      European rabbit 12 million years ago. Approximately 25 VDJ gene sequences were
      obtained for each one of three Lepus europaeus individuals. We found that Lepus
      also uses the VHn genes in 5-10 % of its VDJ rearrangements. Our results show
      that the VHn genes are a conserved ancestral polymorphism that has been
      maintained in the leporids genome and is being used for the generation of VDJ
      rearrangements by both modern Lepus and Oryctolagus.

PMID- 23974324
TI  - Seasonal pattern of avian Plasmodium-infected mosquitoes and implications for
      parasite transmission in central Panama.
AB  - Aedeomyia squamipennis and Culex (Melanoconion) ocossa, two ubiquitous
      Neotropical mosquito species, are likely involved in the transmission of several
      bird pathogens in Gamboa, central Panama. However, knowledge on their eco
      epidemiological profiles is still incomplete. Our goal in this study was to
      investigate temporal trends of vector density and their relationship with avian
      plasmodia prevalence. This information is central to identifying the risk posed
      by each vector species to the avian community locally. We found that A.
      squamipennis maintains stable population size across climatic seasons and thus
      maybe a more efficient vector of avian malaria than C. ocossa. In contrast, C.
      ocossa, which undergoes considerable population expansion in the rainy season and
      contraction in the dry season, is likely only an important avian malaria vector
      during part of the year. This is consistent with the larger number of parasite
      isolations and Plasmodium cyt b lineages recovered from A. squamipennis than from
      C. ocossa and might be explained by marked differences in their seasonality and
      host-feeding preferences. More Plasmodium PCR testing in mosquito communities
      from other areas of Panama might reveal additional vectors of avian plasmodia. 

PMID- 23974325
TI  - The further spread of Aedes japonicus japonicus (Diptera, Culicidae) towards
      northern Germany.
AB  - After its first detection in 2008 in the south German federal state of Baden
      Wuerttemberg, another distinct population of the invasive Asian bush mosquito
      Aedes japonicus japonicus was unexpectedly found in western Germany in 2012.
      Range expansion had already been observed for the southern German population and
      was anticipated for the western German one. Here, we report on a third,
      apparently independent and even more northerly German colonization area of Aedes
      j. japonicus in southern Lower Saxony and northeastern North Rhine-Westphalia,
      which was discovered in spring 2013. In a snapshot study, intended to determine
      the presence or absence of Aedes j. japonicus in an area close to Hanover, the
      capital of the northern German federal state of Lower Saxony, where a specimen
      had been collected in late 2012, central water basins of cemeteries were checked
      for pre-imaginal mosquito stages at the beginning of the mosquito season 2013.
      Almost 20% of the inspected cemeteries were found positive (25 out of 129), with
      many of them being located in towns and villages close to the motorways A2 and
      A7. Being of Far Eastern origin, the Asian bush mosquito is well adapted to
      moderate climates and appears to be further expanding its distribution area in
      Central Europe. As it is a proven laboratory vector of several mosquito-borne
      disease agents, its present and future distribution areas should be carefully
      monitored.

PMID- 23974326
TI  - The description and histopathology of Leptorhynchoides polycristatus n. sp.
      (Acanthocephala: Rhadinorhynchidae) from sturgeons, Acipenser spp.
      (Actinopterygii: Acipenseridae) in the Caspian Sea, Iran, with emendation of the
      generic diagnosis.
AB  - Of the three known species of Leptorhynchoides Kostylew 1924, two are reported
      from North American fishes: Leptorhynchoides aphredoderi Buckner and Buckner 1976
      and Leptorhynchoides thecatus (Linton 1891) Kostylew 1924. The third species,
      Leptorhynchoides plagicephalus (Westrumb 1821) Kostylew 1924, is commonly found
      in the Caspian and Black Sea from at least four species of sturgeons including
      Acipenser stellatus Pallas 1771 and the Acipenser nudiventris Lovetzsky 1828 from
      which Leptorhynchoides polycristatus n. sp. was found. No taxonomic work has been
      reported for L. plagicephalus for the last 90 years. L. polycristatus n. sp. can
      be readily confused with L. plagicephalus because of many superficial
      similarities. Such similarities include the general shape of the trunk,
      proboscis, and organ systems. However, L. polycristatus is clearly distinguished
      from the other three species primarily by having (1) 19-20 proboscis hooks per
      row; (2) the shortest hooks are anterior and the longest at the middle; the
      opposite is true in L. plagicephalus; (3) with a cuticular collar enveloping the
      base of the proboscis hooks; (4) the surface of its proboscis hooks is ribbed;
      (5) with a broad collar of multiple rectangular cuticular crests encircling the
      anterior end of the trunk; this is the only member of Leptorhynchoides with such
      a structure; (6) with many large ovoid uninucleated cells in the subcuticular
      layer of the trunk; (7) with paired glandular clusters near the male reproductive
      opening and of suction cup-like sensory structures on the bursa; (8) with
      dorsoventral ligament across the vagina; (9) cement glands are in a cluster of
      eight arranged in two horizontal tiers of four glands each; (10) with female
      gonopore near terminal; (11) with structures interpreted as possible microtriches
      on the surface of the trunk; (12) and with thinner eggs. L. polycristatus caused
      extensive histopathological damage to host intestinal layers. The armed proboscis
      invades and attaches to the host mucosa causing villi compression and necrosis of
      the epithelial lining with subsequent hemorrhaging and granulocyte migration. No
      encapsulation of the acanthocephalan is visible, and the worm can migrate deep
      into the smooth muscle layers of the muscularis extrema. The presence of L.
      polycristatus in the lumen of the host intestine obstructs and damages the
      absorbing surface of the host affecting the nutritional potential. Dead, necrotic
      host epithelial tissue and remnants of villi and crypts are visible.

PMID- 23974327
TI  - Genetic integration of local dispersal and exploratory behaviour in a wild bird.
AB  - Dispersal is a major determinant of the ecological and evolutionary dynamics of
      natural populations. Individuals differ greatly in the likelihood and distance of
      dispersal, but it is generally unclear to what extent intrinsic, possibly
      genetic, differences contribute. Here we present the first explicit empirical
      evidence for genetic coupling of local dispersal and exploratory behaviour, a key
      'animal personality' trait. Using relatedness data from a multi-generation
      pedigree of free-living great tits (Parus major), we find quantitative genetic
      variation for both the distance of local dispersal within our study area and the
      rate at which individuals explore a novel environment. Moreover, we find a
      strongly positive genetic correlation between local dispersal distance and
      exploration rate, despite a weak and non-significant phenotypic correlation.
      These findings demonstrate a potentially important behavioural mechanism
      underlying heritable differences in local dispersal and highlight the potential
      for concerted evolution of dispersal and animal personality in response to
      selection. 

PMID- 23974328
TI  - Tonsillotomy: it's time to clarify the facts.

PMID- 23974329
TI  - Chronic vocal cord palsy in Thuringia, Germany: a population-based study on
      epidemiology and outcome.
AB  - Although surgical treatment of patients with chronic vocal cord palsy (VCP) is an
      integral part of clinical routine of otorhinolaryngologists, there is nearly no
      population-based data published on incidence and efficiency of this surgery
      country-wide or nation-wide. 1430 patients with chronic VCP were treated in a
      department of otorhinolaryngology between 2005 and 2010 in Thuringia, Germany.
      VCP was unilateral and bilateral in 63 and 18%, respectively. The affected side
      was not documented in 20%. Iatrogenic lesions of the recurrent nerve (42%) and
      neoplastic infiltration (27%) were the leading etiologies. 192 patients (13%)
      received surgical treatment. 31% of patient needed more than one surgery. The
      rate of surgeries was higher for bilateral VCP (p < 0.0001). Vocal cord
      augmentation was the most frequent surgery for unilateral VCP and posterior
      cordectomy for bilateral VCP. The complication rate was high (16%), but not
      different between unilateral and bilateral VCP (p = 0.108). The risk for
      tracheostomy was higher in the bilateral VCP group (p < 0.0001). Voice
      improvement was better after treatment of unilateral VCP (p < 0.0001). Breathing
      improvement was more frequent after bilateral VCP (p = 0.028). Dysphagia did not
      improve significantly. The rate of better voice, breathing, and swallowing
      function was higher in patients treated surgically than without surgery (all p <
      0.0001). The rate of patients admitted for treatment of vocal fold palsy was
      9.9/100,000 habitants. The surgical rate of VCP was 1.38/100,000 habitants. This
      population-based analysis shows that surgery for VCP is performed with higher
      incidence than expected effectively, but with relevant risks in daily routine of
      otorhinolaryngologists.

PMID- 23974330
TI  - Well and intermediate differentiated laryngeal chondrosarcoma: toward
      conservative surgery?
AB  - Chondrosarcoma of the larynx is a relatively rare malignant tumor. In the world
      literature, only 600 cases of laryngeal chondrosarcoma (LCS) have been reported.
      It is the most frequent non-epithelial tumor of the larynx (0.07-2% of all
      cancers), usually occurring on the cricoid. We present six cases of well
      intermediate differentiated grade chondrosarcoma of the larynx, diagnosed between
      the fifth and seventh decades of life, in the absence of relevant risk factors.
      All cases were subjected to a conservative surgical approach, either endoscopic
      using remodeling transoral laser surgery, or open neck via a supratracheal
      partial laryngectomy (STL), sparing laryngeal function. All patients are free
      from recurrence with a minimum follow-up of 31 months. All were ultimately
      decannulated, are able to tolerate a quite normal diet and to speak
      satisfactorily. Conservative laryngeal surgery is effective because
      chondrosarcoma is often a low-grade tumor showing slow growth. The criteria for
      choosing the type of surgery was based on the age of the patient (elderly patient
      > favoring an endoscopic approach), on the rate of involvement of the cricoid and
      on the involvement of the cricoarytenoid joints (if possible to save a
      cricoarytenoid unit > favoring a STL). By extending the inferior limit of the
      resection to include a large part of the cricoid cartilage, supratracheal partial
      laryngectomies expanded the indications to some LCSs not involving the entire
      cricoid lamina sparing laryngeal function and avoiding the need for total
      laryngectomy.

PMID- 23974331
TI  - Validation of the Italian version of the singing voice handicap index.
AB  - Singers constitute a specific population that is particularly sensitive to vocal
      disability, which may have a higher impact on their quality of life compared to
      non-singers. A specific questionnaire, the Singing Voice Handicap Index (SVHI),
      was created and validated aimed to measure the physical, social, emotional and
      economic impacts of voice problems on the lives of singers. The aim of this study
      was to validate the Italian version of the SVHI. The validated English version of
      the SVHI was translated into Italian and then discussed with several voice care
      professionals. The Italian version of the SVHI was administered to 214
      consecutive singers (91 males and 123 females, mean age: 32.62 +/- 10.85). Voice
      problem complaints were expressed by 97 of the singers, while 117 were healthy
      and had no voice conditions. All subjects underwent a phoniatric consultation
      with videolaryngostroboscopy to ascertain the condition of the vocal folds.
      Internal consistency of the Italian version of the SVHI showed a Cronbach's alpha
      of 0.97. The test-retest reliability was assessed by comparing the responses
      obtained by all subjects in two different administrations of the questionnaire;
      the difference was not significant (p = ns). The SVHI scores in healthy singers
      was significantly lower than the one obtained in the group of singers with a
      vocal fold abnormality (29.26 +/- 25.72 and 45.62 +/- 27.95, p < 0.001,
      respectively). The Italian version of the SVHI was successfully validated as an
      instrument with proper internal consistency and reliability. It is a suitable
      instrument for the self-evaluation of handicaps related to voice problems in the
      context of singing.

PMID- 23974332
TI  - Endonasal resection of early stage squamous cell carcinoma of the nasal
      vestibule.
AB  - The squamous cell carcinoma of the nasal vestibule (SCCNV) is a comparatively
      rare malignant disease. It occurs in the transition zone at the limen nasi. The
      choice of treatment for small tumors is a matter of controversy. Due to better
      cosmetic results, radiation therapy is usually recommended, however some recent
      reports have suggested that early stage tumors are equally or even more
      effectively managed by surgery. There was no standardized surgical procedure
      applied in these studies, though. The goal of our investigation was the
      retrospective evaluation of patients with a T1 or T2 carcinoma of the nasal
      vestibule who were treated surgically with an endonasal, endoscope-controlled
      approach at our ENT clinic between 2008 and 2010. Given the rarity of SCCNV, the
      10 included cases represent the largest group of patients with early stage SCCNV
      treated primarily surgically by an endonasal approach so far. Our study shows
      that the endonasal resection of an early stage vestibular carcinoma seems
      adequate as a possible therapy. In the follow-up observation period no local or
      loco-regional recurrence was observed. The external cosmetic damage and endonasal
      scarring do not appear to be pronounced even following cartilage resection and
      were regarded as not seriously disadvantageous. 

PMID- 23974333
TI  - Structure-activity relationships in Toll-like receptor 7 agonistic 1H-imidazo[4,5
      c]pyridines.
AB  - Engagement of TLR7 in plasmacytoid dendritic cells leads to the induction of IFN
      alpha/beta which plays essential functions in the control of adaptive immunity.
      We had previously examined structure-activity relationships (SAR) in TLR7/8
      agonistic imidazoquinolines with a focus on substituents at the N(1), C(2), N(3)
      and N(4) positions, and we now report SAR on 1H-imidazo[4,5-c]pyridines. 1-Benzyl
      2-butyl-1H-imidazo[4,5-c]pyridin-4-amine was found to be a pure TLR7-agonist with
      negligible activity on TLR8. Increase in potency was observed in N(6)-substituted
      analogues, especially in those compounds with electron-rich substituents. Direct
      aryl-aryl connections at C6 abrogated activity, but TLR7 agonism was reinstated
      in 6-benzyl and 6-phenethyl analogues. Consistent with the pure TLR7-agonistic
      behavior, prominent IFN-alpha induction in human PBMCs was observed with minimal
      proinflammatory cytokine induction. A benzologue of imidazoquinoline was also
      synthesized which showed substantial improvements in potency over the parent
      imidazopyridine. Distinct differences in N(6)-substituted analogues were observed
      with respect to IFN-alpha induction in human PBMCs on the one hand, and CD69
      upregulation in lymphocytic subsets, on the other. 

PMID- 23974335
TI  - Does nurse manager education really matter?

PMID- 23974336
TI  - Clinical and operational collaboration in value analysis.

PMID- 23974337
TI  - On the spot! Peer validation of BP measurement competence.

PMID- 23974338
TI  - The realities of accountability.

PMID- 23974339
TI  - Combating workplace violence with peer mentoring.

PMID- 23974341
TI  - Finding your way...data to decision.

PMID- 23974342
TI  - Decision making through the ethics lens.

PMID- 23974343
TI  - Hiring right, every time.

PMID- 23974344
TI  - Are you ready for The Joint Commission survey?

PMID- 23974345
TI  - Interfacial growth of large-area single-layer metal-organic framework nanosheets.
AB  - The air/liquid interface is an excellent platform to assemble two-dimensional
      (2D) sheets of materials by enhancing spontaneous organizational features of the
      building components and encouraging large length scale in-plane growth. We have
      grown 2D molecularly-thin crystalline metal-organic-framework (MOF) nanosheets
      composed of porphyrin building units and metal-ion joints (NAFS-13) under
      operationally simple ambient conditions at the air/liquid interface. In-situ
      synchrotron X-ray diffraction studies of the formation process performed directly
      at the interface were employed to optimize the NAFS-13 growth protocol leading to
      the development of a post-injection method -post-injection of the metal
      connectors into the water subphase on whose surface the molecular building blocks
      are pre-oriented- which allowed us to achieve the formation of large-surface area
      morphologically-uniform preferentially-oriented single-layer nanosheets. The
      growth of such large-size high-quality sheets is of interest for the
      understanding of the fundamental physical/chemical properties associated with
      ultra-thin sheet-shaped materials and the realization of their use in
      applications. 

PMID- 23974346
TI  - Optimized goniometer for determination of the scattering phase function of
      suspended particles: simulations and measurements.
AB  - We present simulations and measurements with an optimized goniometer for
      determination of the scattering phase function of suspended particles. We applied
      the Monte Carlo method, using a radially layered cylindrical geometry and
      mismatched boundary conditions, in order to investigate the influence of
      reflections caused by the interfaces of the glass cuvette and the scatterer
      concentration on the accurate determination of the scattering phase function.
      Based on these simulations we built an apparatus which allows direct measurement
      of the phase function from theta=7  deg to theta=172  deg without any need for
      correction algorithms. Goniometric measurements on polystyrene and SiO2 spheres
      proved this concept. Using the validated goniometer, we measured the phase
      function of yeast cells, demonstrating the improvement of the new system compared
      to standard goniometers. Furthermore, the scattering phase function of different
      fat emulsions, like Intralipid, was determined precisely.

PMID- 23974347
TI  - Comparison of cerebral tissue oxygenation values in full term and preterm
      newborns by the simultaneous use of two near-infrared spectroscopy devices: an
      absolute and a relative trending oximeter.
AB  - The aim of this study is to compare a two-wavelength light emitting diode-based
      tissue oximeter (INVOS), which is designed to show trends in tissue oxygenation,
      with a four-wavelength laser-based oximeter (FORE-SIGHT), designed to deliver
      absolute values of tissue oxygenation. Simultaneous values of cerebral tissue
      oxygenation (StO2) are measured using both devices in 15 term and 15 preterm
      clinically stable newborns on the first and third day of life. Values are
      recorded simultaneously in two periods between which oximeter sensor positions
      are switched to the contralateral side. Agreement between StO2 values before and
      after the change of sensor position is analyzed. We find that mean cerebral StO2
      values are similar between devices for term and preterm babies, but INVOS shows
      StO2 values spread over a wider range, with wider standard deviations than shown
      by the FORE-SIGHT. There is relatively good agreement with a bias up to 3.5% and
      limits of agreement up to 11.8%. Measurements from each side of the forehead show
      better repeatability for the FORE-SIGHT monitor. We conclude that performance of
      the two devices is probably acceptable for clinical purposes. Both performed
      sufficiently well, but the use of FORE-SIGHT may be associated with tighter range
      and better repeatability of data.

PMID- 23974348
TI  - Conservation of the 2-keto-3-deoxymanno-octulosonic acid (Kdo) biosynthesis
      pathway between plants and bacteria.
AB  - The increasing prevalence of multi-drug resistant bacteria is driving efforts in
      the development of new antibacterial agents. This includes a resurgence of
      interest in the Gram-negative bacteria lipopolysaccharide (LPS) biosynthesis
      enzymes as drug targets. The six carbon acidic sugar 2-keto-3-deoxymanno
      octulosonic acid (Kdo) is a component of the lipid A moiety of the LPS in Gram
      negative bacteria. In most cases the lipid A substituted by Kdo is the minimum
      requirement for cell growth, thus presenting the possibility of targeting either
      the synthesis or incorporation of Kdo for the development of antibacterial
      agents. Indeed, potent in vitro inhibitors of Kdo biosynthesis enzymes have been
      reported but have so far failed to show sufficient in vivo action against Gram
      negative bacteria. As part of an effort to design more potent antibacterial
      agents targeting Kdo biosynthesis, the crystal structures of the key Kdo
      biosynthesis enzymes from Escherichia coli have been solved and their structure
      based mechanisms characterized. In eukaryotes, Kdo is found as a component of the
      pectic polysaccharide rhamnogalacturonan II in the plant primary cell wall.
      Interestingly, despite incorporating Kdo into very different macromolecules the
      Kdo biosynthesis and activation pathway is almost completely conserved between
      plants and bacteria. This raises the possibility for plant research to exploit
      the increasingly detailed knowledge and resources being generated by the
      microbiology community. Likewise, insights into Kdo biosynthesis in plants will
      be potentially useful in efforts to produce new antimicrobial compounds. 

PMID- 23974349
TI  - The flip side of doxorubicin: Inflammatory and tumor promoting cytokines.
AB  - Cardiac toxicity is a major dose-limiting factor for the anthracycline drug
      doxorubicin. The reasons why doxorubicin causes heart damage are not fully
      understood, and the manuscript by Wong et al. postulates that inflammatory
      cytokines released from macrophages or other cell types may play a significant
      role in the damage process in response to doxorubicin and possibly other
      chemotherapeutic agents.(1) Expression of many cytokines requires activation of
      both the p38 MAPK and JNK pathways and, additionally, doxorubicin toxicity can be
      blocked by combined inhibition of both pathways.(2,3) The MAP3K responsible for
      doxorubicin-induced p38 MAPK and JNK activation in keratinocytes was previously
      shown by these authors to be ZAK.(4) ZAK is of note because it can be targeted by
      FDA approved agents such as nilotinib and sorafenib.(4-7)

PMID- 23974351
TI  - Is local participation always optimal for sustainable action? The costs of
      consensus-building in Local Agenda 21.
AB  - Is local participation always optimal for sustainable action? Here, Local Agenda
      21 is a relevant case as it broadly calls for consensus-building among
      stakeholders. Consensus-building is, however, costly. We show that the costs of
      making local decisions are likely to rapidly exceed the benefits. Why? Because as
      the number of participants grows, the more likely it is that the group will
      include individuals who have an extreme position and are unwilling to make
      compromises. Thus, the net gain of self-organization should be compared with
      those of its alternatives, for example voting, market-solutions, or not making
      any choices at all. Even though the informational value of meetings may be
      helpful to policy makers, the model shows that it also decreases as the number of
      participants increase. Overall, the result is a thought provoking scenario for
      Local Agenda 21 as it highlights the risk of less sustainable action in the
      future. 

PMID- 23974352
TI  - Population-based reference values for the 1-min sit-to-stand test.
AB  - OBJECTIVES: To determine reference values for the 1-min sit-to-stand (STS) test
      in an adult population. METHODS: Cross-sectional study nested within a nationwide
      health promotion campaign in Switzerland. Adults performed the STS test and
      completed questions on demographics and health behavior. RESULTS: 6,926 out of
      7,753 (89.3 %) adults were able to complete the STS test. The median number of
      repetitions ranged from 50/min (25-75th percentile 41-57/min) in young men and
      47/min (39-55/min) in young women aged 20-24 years to 30/min (25-37/min) in older
      men and 27/min (22-30/min) in older women aged 75-79 years. CONCLUSIONS: The
      reference values support the interpretation of 1-min STS test performance and
      identification of subjects with decreased lower body muscular strength and
      endurance.

PMID- 23974353
TI  - The female health-survival advantage: paradox unwarranted.

PMID- 23974350
TI  - Recent insights into Candida albicans biofilm resistance mechanisms.
AB  - Like other microorganisms, free-living Candida albicans is mainly present in a
      three-dimensional multicellular structure, which is called a biofilm, rather than
      in a planktonic form. Candida albicans biofilms can be isolated from both abiotic
      and biotic surfaces at various locations within the host. As the number of
      abiotic implants, mainly bloodstream and urinary catheters, has been increasing,
      the number of biofilm-associated bloodstream or urogenital tract infections is
      also strongly increasing resulting in a raise in mortality. Cells within a
      biofilm structure show a reduced susceptibility to specific commonly used
      antifungals and, in addition, it has recently been shown that such cells are less
      sensitive to killing by components of our immune system. In this review, we
      summarize the most important insights in the mechanisms underlying biofilm
      associated antifungal drug resistance and immune evasion strategies, focusing on
      the most recent advances in this area of research. 

PMID- 23974354
TI  - Exogenous application of hydrogen sulfide donor sodium hydrosulfide enhanced
      multiple abiotic stress tolerance in bermudagrass (Cynodon dactylon (L). Pers.).
AB  - As a gaseous molecule, hydrogen sulfide (H2S) has been recently found to be
      involved in plant responses to multiple abiotic stress. In this study, salt (150
      and 300 mM NaCl), osmotic (15% and 30% PEG6000) and cold (4  degrees C) stress
      treatments induced accumulation of endogenous H2S level, indicating that H2S
      might play a role in bermudagrass responses to salt, osmotic and cold stresses.
      Exogenous application of H2S donor (sodium hydrosulfide, NaHS) conferred improved
      salt, osmotic and freezing stress tolerances in bermudagrass, which were
      evidenced by decreased electrolyte leakage and increased survival rate under
      stress conditions. Additionally, NaHS treatment alleviated the reactive oxygen
      species (ROS) burst and cell damage induced by abiotic stress, via modulating
      metabolisms of several antioxidant enzymes [catalase (CAT), peroxidase (POD) and
      GR (glutathione reductase)] and non-enzymatic glutathione antioxidant pool and
      redox state. Moreover, exogenous NaHS treatment led to accumulation of osmolytes
      (proline, sucrose and soluble total sugars) in stressed bermudagrass plants.
      Taken together, all these data indicated the protective roles of H2S in
      bermudagrass responses to salt, osmotic and freezing stresses, via activation of
      the antioxidant response and osmolyte accumulation. These findings might be
      applicable to grass and crop engineering to improve abiotic stress tolerance.

PMID- 23974355
TI  - Alleviation of silver toxicity by calcium chloride (CaCl2) in Lemna gibba L.
AB  - The toxicity effects of silver (Ag) and the protective role of calcium chloride
      (CaCl2) was studied in Lemna gibba L. (L. gibba) plants. Silver speciation showed
      that silver toxicity in L. gibba culture medium can be attributed to free ionic
      Ag(+) concentration. Frond abscission, intracellular reactive oxygen species
      (ROS) formation and intracellular uptake of Ag(+) were investigated when L. gibba
      plants were exposed to AgNO3 concentrations (0.5, 1, 5, and 10 MUM) supplemented
      or not by 10 MUM CaCl2. An increase in frond abscission, intracellular ROS and
      intracellular uptake of Ag(+) were detected in L. gibba plants for all tested
      concentrations of AgNO3 after 24 h treatment. However, addition of 10 MUM CaCl2
      to the L. gibba culture medium reduced the toxic effects of Ag by decreasing
      silver uptake into the plant and intracellular ROS formation. The results suggest
      that Ag-induced toxicity was attributed to Ag(+) accumulation and chloride was
      able to protect L. gibba plants against Ag toxicity by formation of complexes
      with Ag and then alleviation of the metal induced oxidative stress.

PMID- 23974356
TI  - A bZIP protein, VIP1, interacts with Arabidopsis heterotrimeric G protein beta
      subunit, AGB1.
AB  - Heterotrimeric G proteins (Galpha, Gbeta, Ggamma) are signaling molecules
      conserved among eukaryotic species. The G proteins transmit signals via protein
      protein interactions. By a yeast two-hybrid screen, we identified a bZIP protein,
      VIP1, as an Arabidopsis thaliana Gbeta (AGB1)-interacting partner. The
      interaction between AGB1 and VIP1 was confirmed by an in vitro GST pull-down
      assay and a bimolecular fluorescence complementation (BiFC) assay. VIP1 was
      previously reported to be a regulator of osmosensory signaling. Interestingly,
      the BiFC pattern between AGB1 and VIP1 was speckled when cells were incubated in
      a hypotonic solution, but not when cells were incubated in a mannitol-containing
      hypertonic solution, suggesting that the subcellular localization of the AGB1
      VIP1 complex is regulated by extracellular osmolarity and/or turgor pressure.

PMID- 23974357
TI  - Globular body production, their anatomy, DNase gel analysis and NDP kinase
      activity in root tips of Poncirus trifoliata L.
AB  - Green globular bodies were developed from Poncirus trifoliata L. root tip
      explants as a response to addition in the substrate of different growth
      regulators. From the globular bodies, shoots initiated and grew. Median section
      of the globular bodies reveals that they are composed of parenchyma cells and
      originate from the pericycle. The activity of DNases during shoot formation from
      globular bodies was influenced by the type and concentration of plant growth
      regulators that were added in the nutrient substrate. Peptide bands formation was
      also influenced by the increase of BA concentration. Consequently, BA, NAA and
      IAA combination influenced 5'-triphosphonucleosides (NTPs) appearance and
      activity in the presence of metal. Peptide bands resulted from the
      electrophoretic analysis of endogenous protein phosphorylation, proved to be
      catalytic subunits of NDP kinases, as they all phosphorylate
      diphosphonucleosides. The enzymes DNases and NDP kinases could be used as a
      scientific tool for the study of shoot formation from P. trifoliata L. green
      globular bodies. 

PMID- 23974358
TI  - Analysis of DNA repair helicase UvrD from Arabidopsis thaliana and Oryza sativa.
AB  - Mismatch repair (MMR) proteins play important roles in maintaining genome
      stability in all the organisms. Studies of MMR genes in plants have identified
      several homologs of the Escherichia coli genes. Crop yield is directly related to
      genome stability, which is crucially required for optimal plant growth and
      development. Numerous genotoxic stresses such as UV light, radiations, pollutants
      and heavy metals cause DNA damage leading to genome instability, which can
      interfere with the plant growth and crop productivity. But the efficient repair
      mechanisms can help to overcome the deleterious effects of the damage. Therefore
      it is important to study the genes involved in various repair pathways in the
      plants in greater detail. UvrD helicase is a component of MMR complex and plays
      an essential role in the DNA repair by providing the unwinding function. In the
      present manuscript we present an in silico analysis of UvrD helicase from two
      plant species (Arabidopsis and rice). The Arabidopsis thaliana and Oryza sativa
      UvrD are 1149 (~129 kDa) and 1165 amino-acids (~130 kDa) proteins, respectively.
      These proteins contain all the conserved domains and are larger than the E. coli
      UvrD because they contain a longer N-terminal extension. In order to decipher the
      role of plant UvrD in various stresses it will be important to study the
      biochemical and functional properties of this enzyme.

PMID- 23974359
TI  - ATP protects against FITC labeling of Solanum lycopersicon and Arabidopsis
      thaliana Ca2+-ATPase ATP binding domains.
AB  - Ca(2+)-ATPases are integral membrane proteins that actively transport Ca(2+)
      against substantial concentration gradients in eukaryotic cells. This active
      transport is energized by coupling ion translocation with ATP hydrolysis. In
      order to better understand this coupling mechanism, we studied the nucleotide
      specificities of isolated ATP binding domains (ABDs) of Solanum lycopersicon
      Ca(2+)-ATPase (LCA), a type IIA non-calmodulin regulated P-type pump found in
      tomato plants that is very similar to mammalian sarco/endoplasmic reticulum
      Ca(2+)-ATPase (SERCA), and Arabidopsis Ca(2+)-ATPase, isoform 2 (ACA2), a type
      IIB calmodulin regulated P-type ATPase found in the endoplasmic reticulum of
      Arabidopsis cells. We used nucleotide protection against FITC labeling as a
      measure of binding since both LCA and ACA contained the KGAP(S,V,F)E motif, which
      has been shown to be modified by fluorescein isothiocyanate (FITC) in P-type
      pumps from animal cells. We demonstrated that the heterologously expressed GST
      tagged ABDs from both LCA and ACA2 were modified by FITC and that ATP protects
      against this modification. Moreover, GTP was able to reduce, but not eliminate,
      the level of FITC labeling in both ABD constructs, suggesting that these plant
      pumps may also bind GTP with low affinity, which is in contrast to mammalian
      SERCA and PMCA type pumps which do not bind GTP. 

PMID- 23974360
TI  - Injection of Sca-1+/CD45+/CD31+ mouse bone mesenchymal stromal-like cells
      improves cardiac function in a mouse myocardial infarct model.
AB  - The objective of this study was to screen mouse bone marrow mesenchymal stromal
      cells (BMSCs) according to expression of cardiac stem cell (CSC) surface antigens
      and to assess the effects of resulting BMSC-like subsets on cardiac function
      after injection in a mouse myocardial infarct model. BMSCs were sorted by
      magnetic beads according to the expression of differentiation antigens on the
      surface of mouse CSCs, and four subsets were identified on the basis of CD45 and
      CD31 expression: stem cell antigen-1+ (Sca-1+)/CD45-/CD31-, Sca-1+/CD45-/CD31+,
      Sca-1+/CD45+/CD31-, and Sca-1+/CD45+/CD31+. When co-cultured with myocardial stem
      cells and 5-aza-2'-deoxycytidine for 14 days, each subset showed expression of
      cardiac markers alpha-actin, connexin 43, desmin, and cardiac troponin I;
      however, expression was greatest in Sca-1+/CD45+/CD31+ cells. To assess the
      ability of these cells to improve cardiac function, each subset was injected
      separately into mice with myocardial infarct induced by ligation of the left
      anterior descending coronary artery, and in vivo cardiac dual inversion recovery
      (DIR) imaging and Doppler echocardiography were performed 48 h, 96 h, and 7 days
      after injection. Results indicated that Sca-1+/CD45+/CD31+ cells were superior in
      improving cardiac function compared with the other subsets and with unsorted
      BMSCs. These results suggest that mouse BMSC cells are polyclonal and that the
      BMSC-like Sca-1+/CD45+/CD31+ subset was effective in directing cardiac
      differentiation and improving cardiac function in mice with myocardial infarcts.

PMID- 23974361
TI  - miR-205 is frequently downregulated in prostate cancer and acts as a tumor
      suppressor by inhibiting tumor growth.
AB  - The purpose of this study was to elucidate the molecular mechanisms of microRNA
      205 (miR-205) as a tumor suppressor in prostate cancer (PCa). In the present
      study, microRNA microarray analysis suggested that the expression of miR-205 was
      significantly decreased in advanced PCa compared with early PCa. Real-time PCR
      analysis also indicated that miR-205 expression was significantly decreased in
      PCa tissues compared with non-cancerous tissues. Moreover, the expression of miR
      205 has been demonstrated to be associated with the clinicopathological stage and
      total/free prostate-specific antigen (PSA) level of PCa. Functional analyses
      showed that both the overexpression of miR-205 and the knockdown of c-SRC in PCa
      cell lines could inhibit cell growth, colony formation, migration, invasion and
      the cell cycle as well as induce cell apoptosis in vitro. Furthermore, over
      expressing miR-205 reduced tumorigenicity in vivo. Through a luciferase activity
      assay and Western blotting, c-SRC was identified as a target of miR-205 in cells.
      The overexpression of miR-205 suppressed c-SRC and its downstream signaling
      molecules, including FAK, p-FAK, ERK1/2 and p-ERK1/2, and attenuated cell
      proliferation, invasion and tumor growth.

PMID- 23974362
TI  - The miRNA let-7a1 inhibits the expression of insulin-like growth factor 1
      receptor (IGF1R) in prostate cancer PC-3 cells.
AB  - Reduced microRNA (miRNA) let-7a expression and the activation of insulin-like
      growth factor-1 receptor (IGF1R) signalling are both involved in prostate cancer
      and progression. In the present study, we demonstrated that the growth inhibitory
      effect of let-7a1 is directly related to targeting IGF1R gene expression in PC-3
      cells. TargetScan predicted three potential target sites (T1, T2 and T3) of let
      7a in the 3' untranslational region (3' UTR) of IGF1R mRNA. Real-time PCR,
      Western blot and luciferase reporter assays were used to detect the effects of
      let-7a1 overexpression or let-7a1 inhibitor on the IGF1R gene expression in PC-3
      cells. The results indicated that let-7a1 could inhibit IGF1R expression by
      directly targeting the T1 and T2 sites in the 3' UTR of the IGF1R mRNA. We then
      used RT-PCR, luciferase reporter assays, 3-(4,5-dimethylthiazol-2-yl)-2,5-
      diphenyl-2H-tetrazolium bromide (MTT) assay, flow cytometry and Hoechst 33342
      staining to examine whether let-7a1-mediated inhibition of IGF1R expression also
      affects the IGF1R-mediated signalling events, including Elk1 activity and c-fos
      gene expression, proliferation, apoptosis and cell cycle. We demonstrated that
      let-7a1-mediated IGF1R downregulation was accompanied by attenuation of Elk1
      activity and c-fos expression, inhibition of cell proliferation, enhanced
      apoptosis and cell cycle arrest, and that loss function of let-7a1 via inhibition
      can upregulate IGF1R accompanied by an increase of Elk1 activity and c-fos
      expression, thereby enhancing cell proliferation. Altogether, these findings
      suggest that let-7a may be novel therapeutic candidate for prostate cancer.

PMID- 23974363
TI  - Chromoplexy: a new paradigm in genome remodeling and evolution.
AB  - Early massively-parallel sequencing studies have revealed the mutational
      landscape of protein-coding genes in prostate cancer. However, most of these
      studies have not explored the extensive influence of genomic rearrangement in
      prostate cancer. In a recent Cell article, Baca and colleagues used whole-genome
      sequencing to tackle this issue, comprehensively surveying the abundance of
      genomic rearrangements present in a large cohort of 57 prostate cancers. They
      characterized a wide-spread phenomenon termed 'chromoplexy', which may drive
      cancer evolution through the phenomena of punctuated equilibrium by concurrently
      dysregulating numerous cancer genes across multiple chromosomes. While the causes
      of this event still require elucidation, this defining discovery undoubtedly
      offers an important glimpse into the evolutionary process of prostate cancer.

PMID- 23974364
TI  - Overexpression of transglutaminase 4 and prostate cancer progression: a potential
      predictor of less favourable outcomes.
AB  - Transglutaminase 4 has been shown to enhance various biological properties of
      prostate cancer cells, e.g., cell-matrix adhesion, invasiveness and the
      epithelial-mesenchymal transition. The objectives of this study were to
      investigate the associations between transglutaminase 4 expression and the
      established features and biochemical recurrence of prostate cancer.
      Transglutaminase 4 immunostaining was performed on a tissue microarray. The
      expression of transglutaminase 4 was evaluated by a scoring method based on the
      intensity and extent of staining. The clinical and pathological information was
      obtained through a review of medical records. Follow-up data were obtained by
      consulting the hospital medical records and the prostate cancer database of our
      department and by contacting patients or family members. We then compared the
      transglutaminase 4 expression levels between the prostate cancer tissues and the
      paracarcinoma tissues and evaluated the correlation of transglutaminase 4
      expression with the clinical parameters and biochemical recurrence of prostate
      cancer. Our results indicated that the transglutaminase 4 staining was
      significantly higher in tumour tissue than in paracarcinoma tissue (P<0.001) and
      was positively associated with higher Gleason score (P<0.001) and higher prostate
      specific antigen level (P=0.005). Patients with transglutaminase 4 overexpression
      experienced shorter biochemical recurrence-free survival after surgery (P=0.042)
      in the univariate analysis but not in the multivariate analysis (P=0.139), which
      indicated that transglutaminase 4 may serve as a potential predictor of
      biochemical recurrence of prostate cancer.

PMID- 23974365
TI  - Genome-scale metabolic model for Lactococcus lactis MG1363 and its application to
      the analysis of flavor formation.
AB  - Lactococcus lactis subsp. cremoris MG1363 is a paradigm strain for lactococci
      used in industrial dairy fermentations. However, despite of its importance for
      process development, no genome-scale metabolic model has been reported thus far.
      Moreover, current models for other lactococci only focus on growth and sugar
      degradation. A metabolic model that includes nitrogen metabolism and flavor
      forming pathways is instrumental for the understanding and designing new
      industrial applications of these lactic acid bacteria. A genome-scale, constraint
      based model of the metabolism and transport in L. lactis MG1363, accounting for
      518 genes, 754 reactions, and 650 metabolites, was developed and experimentally
      validated. Fifty-nine reactions are directly or indirectly involved in flavor
      formation. Flux Balance Analysis and Flux Variability Analysis were used to
      investigate flux distributions within the whole metabolic network. Anaerobic
      carbon-limited continuous cultures were used for estimating the energetic
      parameters. A thorough model-driven analysis showing a highly flexible nitrogen
      metabolism, e.g., branched-chain amino acid catabolism which coupled with the
      redox balance, is pivotal for the prediction of the formation of different flavor
      compounds. Furthermore, the model predicted the formation of volatile sulfur
      compounds as a result of the fermentation. These products were subsequently
      identified in the experimental fermentations carried out. Thus, the genome-scale
      metabolic model couples the carbon and nitrogen metabolism in L. lactis MG1363
      with complete known catabolic pathways leading to flavor formation. The model
      provided valuable insights into the metabolic networks underlying flavor
      formation and has the potential to contribute to new developments in dairy
      industries and cheese-flavor research. 

PMID- 23974366
TI  - Expression of the endogenous and heterologous clavulanic acid cluster in
      Streptomyces flavogriseus: why a silent cluster is sleeping.
AB  - Clusters for clavulanic acid (CA) biosynthesis are present in the actinomycetes
      Streptomyces flavogriseus ATCC 33331 and Saccharomonospora viridis DSM 43017.
      These clusters, which are silent, contain blocks of conserved genes in the same
      order as those of the Streptomyces clavuligerus CA cluster but assembled in a
      different organization. S. flavogriseus was grown in nine different media, but
      clavulanic acid production was undetectable using bioassays or by high
      performance liquid chromatography analyses. Reverse-transcriptase polymerase
      chain reaction (RT-PCR) of S. flavogriseus CA biosynthesis genes showed that the
      regulatory genes ccaR and claR and some biosynthetic genes were expressed whereas
      expression of cyp, orf12, orf13, and oppA2 was undetectable. The ccaR gene of S.
      clavuligerus was unable to switch on CA production in S. flavogriseus::[Pfur-ccaR
      C], but insertion of a cosmid carrying the S. clavuligerus CA cluster (not
      including the ccaR gene) conferred clavulanic acid production on S.
      flavogriseus::[SCos-CA] particularly in TBO and YEME media; these results
      suggests that some of the S. flavogriseus CA genes are inactive. The known
      heptameric sequences recognized by CcaR in S. clavuligerus are poorly or not
      conserved in S. flavogriseus. Quantitative RT-PCR analysis of the CA gene
      clusters of S. clavuligerus and S. flavogriseus showed that the average
      expression value of the expressed genes in the former strain was in the order of
      1.68-fold higher than in the later. The absence of CA production by S.
      flavogriseus can be traced to the lack of expression of the essential genes cyp,
      orf12, orf13, orf14, and oppA2. Heterologous expression of S. clavuligerus CA
      gene cluster in S. flavogriseus::[SCos-CA] was 11- to 14-fold lower than in the
      parental strain, suggesting that the genetic background of the host strain is
      important for optimal production of CA in Streptomyces.

PMID- 23974367
TI  - Decolorization of textile azo dye and Congo red by an isolated strain of the
      dissimilatory manganese-reducing bacterium Shewanella xiamenensis BC01.
AB  - Shewanella xiamenensis BC01 (SXM) was isolated from sediment collected off
      Xiamen, China and was identified based on the phylogenetic tree of 16S rRNA
      sequences and the gyrB gene. This strain showed high activity in the
      decolorization of textile azo dyes, especially methyl orange, reactive red 198,
      and recalcitrant dye Congo red, decolorizing at rates of 96.2, 93.0, and 87.5%,
      respectively. SXM had the best performance for the specific decolorization rate
      (SDR) of azo dyes compared to Proteus hauseri ZMd44 and Aeromonas hydrophila
      NIU01 strains and had an SDR similar to Shewanella oneidensis MR-1 in Congo red
      decolorization. Luria-Bertani medium was the optimal culture medium for SXM, as
      it reached a density of 4.69 g-DCW L(-1) at 16 h. A mediator (manganese)
      significantly enhanced the biodegradation and flocculation of Congo red. Further
      analysis with UV-VIS, Fourier Transform Infrared spectroscopy, and Gas
      chromatography-mass spectrometry demonstrated that Congo red was cleaved at the
      azo bond, producing 4,4'-diamino-1,1'-biphenyl and 1,2'-diamino naphthalene 4
      sulfonic acid. Finally, SEM results revealed that nanowires exist between the
      bacteria, indicating that SXM degradation of the azo dyes was coupled with
      electron transfer through the nanowires. The purpose of this work is to explore
      the utilization of a novel, dissimilatory manganese-reducing bacterium in the
      treatment of wastewater containing azo dyes.

PMID- 23974368
TI  - Composition diversity and nutrition conditions for accumulation of
      polyhydroxyalkanoate (PHA) in a bacterial community from activated sludge.
AB  - We investigated the effect of chemical oxygen demand (COD)/N ratio on
      polyhydroxybutyrate (PHB) accumulating ability in an anaerobic/aerobic cycle
      sequential batch reactor (SBR). Compared the COD/N ratio of 10, 20, 50, and 125,
      the COD/N of 125 was the most suitable nutritional proportion. When COD was 1,200
      mg/L and COD/N/P was 1,200/9.6/30, activated sludge PHB synthesis reached a
      maximum of 64.2 % of the dry weight of the cells. The population of the activated
      sludge was detected periodically by denaturing gradient gel electrophoresis
      (DGGE). The predominant strains belonged to five genera: Bacteroidetes sp.,
      Acinetobacter sp., Betaproteobacteria sp., Gammaproteobacteria sp., Arcobacter
      sp., and Bacillus sp. Pyrosequencing analysis of the 16S rRNA gene indicated that
      the PHB synthesis community was more diverse than that was detected by DGGE,
      specifically Acidobacteria (12.25 %), Alphaproteobacteria (10.78 %),
      Actinomycetales (9.68 %), Actinobacteria (5.15 %), Proteobacteria (4.04 %), and
      unclassified bacteria (24.14 %).

PMID- 23974369
TI  - Biases in community structures of ammonia/ammonium-oxidizing microorganisms
      caused by insufficient DNA extractions from Baijiang soil revealed by comparative
      analysis of coastal wetland sediment and rice paddy soil.
AB  - Repetitive extraction of DNAs from surface sediments of a coastal wetland in Mai
      Po Nature Reserve (MP) of Hong Kong and surface Baijiang soils from a rice paddy
      (RP) in Northeast China was conducted to compare the microbial diversity in this
      study. Community structures of ammonia/ammonium-oxidizing microorganisms in these
      samples were analyzed by PCR-DGGE technique. The diversity and abundance of
      ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), and anaerobic
      ammonium-oxidizing (anammox) bacteria were also analyzed based on archaeal and
      bacterial ammonia monooxygenase subunit A encoding (amoA) and anammox bacterial
      16S rRNA genes, respectively. DGGE profiles of archaeal and bacterial amoA and
      anammox bacterial 16S rRNA genes showed a similar pattern among all five
      repetitively extracted DNA fractions from both MP and RP, except the anammox
      bacteria in RP, indicating a more diverse anammox community retrieved in the
      second to the fifth fractions than the first one. Both soil and marine group AOA
      were detected while soil and coastal group AOB and Scalindua-anammox bacteria
      were dominant in MP. Soil group AOA and marine group AOB were dominant in RP,
      while both Scalindua and Kuenenia species were detected in RP. Pearson
      correlation analysis showed that the abundance of archaeal and bacterial amoA and
      anammox bacterial 16S rRNA genes was significantly correlated with the DNA
      concentrations of the five DNA fractions from MP, but not from RP (except the
      archaeal amoA gene). Results suggest that anammox bacteria diversity may be
      biased by insufficient DNA extraction of rice paddy soil samples. 

PMID- 23974370
TI  - Efficient production of deoxynucleoside-5'-monophosphates using deoxynucleoside
      kinase coupled with a GTP-regeneration system.
AB  - Deoxynucleoside-5'-monophosphates (5'-dNMPs) are the basic components of DNA and
      are widely used in medicine and as chemical and biochemical reagents. A large
      amount of effort has been expended to obtain 5'-dNMPs of high quality and at a
      low cost. However, these procedures are inefficient and inconvenient. In this
      study, deoxyadenosine-5'-monophosphate (5'-dAMP), 2,6-diaminopurine
      deoxynucleoside-5'-monophosphate (5'-dDAMP), and deoxycytidine-5'-monophosphate
      (5'-dCMP) were biosynthesized using recombinant N-deoxyribosyltransferase II (NDT
      II), deoxycytidine kinase, and acetate kinase in a one-pot reaction system. The
      ndt-II gene from Lactobacillus delbrueckii, dck from Bacillus subtilus, and ack
      from Escherichia coli K12 were overexpressed in E. coli BL21 (DE3). Thymidine was
      used as the deoxyribose donor; GTP was used as the phosphate donor, and acetyl
      phosphate was used to regenerate GTP. Under optimized conditions, each 10 mM
      adenine, 10 mM 2,6-diaminopurine, or 10 mM cytosine were converted into 9.01 mM
      5'-dAMP, 8.68 mM 5'-dDAMP, or 6.23 mM 5'-dCMP, respectively. The high yield
      indicated that this process of biosynthesis of 5'-dAMP, 5'-dDAMP, or 5'-dCMP was
      efficient and economical, and this one-pot system may also potentially be used
      for the preparation of other types of 5'-dNMPs.

PMID- 23974371
TI  - Engineering chimeric thermostable GH7 cellobiohydrolases in Saccharomyces
      cerevisiae.
AB  - We report here the effect of adding different types of carbohydrate-binding
      modules (CBM) to a single-module GH7 family cellobiohydrolase Cel7A from a
      thermophilic fungus Talaromyces emersonii (TeCel7A). Both bacterial and fungal
      CBMs derived from families 1, 2 and 3, all reported to bind to crystalline
      cellulose, were used. Chimeric cellobiohydrolases with an additional S-S bridge
      in the catalytic module of TeCel7A were also made. All the fusion proteins were
      secreted in active form and in good yields by Saccharomyces cerevisiae. The
      purified chimeric enzymes bound to cellulose clearly better than the catalytic
      module alone and demonstrated high thermal stability, having unfolding
      temperatures (T m) ranging from 72  degrees C to 77  degrees C. The highest
      activity enhancement on microcrystalline cellulose could be gained by a fusion
      with a bacterial CBM3 derived from Clostridium thermocellum cellulosomal
      scaffolding protein CipA. The two CBM3 fusion enzymes tested were more active
      than the reference enzyme Trichoderma reesei Cel7A both at moderate (45  degrees
      C and 55  degrees C) and at high temperatures (60  degrees C and 65  degrees C),
      the hydrolysis yields being two- to three-fold better at 60  degrees C, and six-
      to seven-fold better at 65  degrees C. The best enzyme variant was also tested on
      a lignocellulosic feedstock hydrolysis, which demonstrated its potency in biomass
      hydrolysis even at 70  degrees C.

PMID- 23974372
TI  - Wishes left unspoken: engaging underserved populations in end-of-life advance
      care planning.
AB  - The end of life can be a highly emotional and difficult time for patients and
      their families. Advance care planning for end-of-life care is one option for
      helping to mitigate the burden of this experience. Despite its advantages, gaps
      in end-of-life advance care planning participation persist, particularly among
      underserved segments of the U.S. population who might benefit from it. This
      column highlights barriers to end-of-life advance care planning among medically
      underserved populations and discusses opportunities for greater engagement. 

PMID- 23974373
TI  - An intersectoral, international policy fellowship experience as a framework for
      faculty development: the marshall memorial fellowship.
AB  - This paper describes the experience of a faculty physician at a historically
      Black medical school who participated in the Marshall Memorial Fellowship, an
      intersectoral, international experience in which emerging leaders explore
      political, economic, social, and cultural institutions. The fellowship
      facilitates collaboration and sharing these experiences within academia and the
      community. 

PMID- 23974374
TI  - The Maternal Infant Health Outreach Worker program in low-income families.
AB  - Vanderbilt University Medical Center's Maternal Infant Health Outreach Worker
      program (MIHOW) is a community-based intervention dedicated to enhancing birth
      outcomes and healthy child development. Trained neighborhood women provide home
      and group services to underserved families in rural and inner city communities.
      This report describes MIHOW's history and work in Tennessee, Kentucky, West
      Virginia, Mississippi, and Louisiana. 

PMID- 23974375
TI  - Implementation of language assessments for staff interpreters in community health
      centers.
AB  - Bilingual staff is used to provide interpreter services in community health
      centers. Little is known about the language proficiency of dual-role staff
      interpreters. Golden Valley Health Centers implemented a formal language
      assessment program to improve the number of qualified dual-role staff
      interpreters and ultimately improve the quality of patient care. 

PMID- 23974376
TI  - An interprofessional collaborative approach in the development of a caries risk
      assessment mobile tablet application: My Smile Buddy.
AB  - BACKGROUND: Given the rising trend in early childhood caries (ECC) and the wide
      disparities that exist in pediatric oral health, risk assessment for ECC has
      become increasingly important. The purpose of this paper is to describe lessons
      learned from an Interprofessional Collaboration (IPC) approach in the planning,
      development, and pilot testing of an electronic interactive ECC risk assessment
      application--My Smile Buddy (MSB). METHODS: Five focus groups were conducted
      during the assessment and development phases of MSB. Community Health Workers
      (CHW) then facilitated MSB with 35 mothers from the local community. RESULTS: MSB
      was well accepted by mothers and scored well in usability and usefulness by CHWs.
      Lessons learned during MSB development included recognizing CHW understanding of
      local community attitudes regarding oral health and access to dental care and
      that power-sharing is required in order to create an intervention that is both
      engaging and accepted by the community.

PMID- 23974377
TI  - The prevalence of trauma and childhood adversity in an urban, hospital-based
      violence intervention program.
AB  - Hospitals represent a promising locus for preventing recurrent interpersonal
      violence and its psychological sequella. We conducted a cross-sectional analysis
      to assess the prevalence of post-traumatic stress disorder (PTSD) and adverse
      childhood experiences (ACEs) among victims of interpersonal violence
      participating in a hospital-based violence intervention program. Participants
      completed PTSD and ACE screenings four to six weeks after violent injury, and
      data were exported from a case management database for analysis. Of the 35
      program participants who completed the ACE and/or PTSD screenings, 75.0% met full
      diagnostic criteria for PTSD, with a larger proportion meeting diagnostic
      criteria for symptom-specific clusters. For the ACE screening, 56.3% reported
      three or more ACEs, 34.5% reported five or more ACEs, and 18.8% reported seven or
      more ACEs. The median ACE score was 3.5. These findings underscore the importance
      of trauma-informed approaches to violence prevention in urban hospitals and have
      implications for emergency medicine research and policy. 

PMID- 23974378
TI  - "Necesita una vacuna": what Spanish-speakers want in text-message immunization
      reminders.
AB  - Appointment reminders help parents deal with complex immunization schedules.
      Preferred content of text-message reminders has been identified for English
      speakers. Spanish-speaking parents of children under three years old were
      recruited to develop Spanish text-message immunization reminders. Structured
      interviews included questions about demographic characteristics, use of
      technology, and willingness to receive text reminders. Each participant was
      assigned to one user-centered design (UCD) test: card sort, needs analysis or
      comprehension testing. Respondents (N=54) were female (70%) and averaged 27 years
      of age (SD=7). A card sort of 20 immunization-related statements resulted in
      identification of seven pieces of critical information, which were compiled into
      eight example texts. These texts were ranked in the needs assessment and the top
      two were assessed for comprehension. All participants were able to understand the
      content and describe intention to act. Utilizing UCD testing, Spanish-speakers
      identified short, specific text content that differed from preferred content of
      English-speaking parents. 

PMID- 23974379
TI  - Barriers to attending an eye examination after vision screening referral within a
      vulnerable population.
AB  - Half of high-risk, uninsured/underinsured individuals identified through vision
      screening as needing eye exams do not attend. Patients who attended vision
      screening and were referred for an exam but did not attend that exam were
      contacted and asked whether they were interested in receiving a free complete eye
      exam at an offsite center within three blocks of the clinic. Those who agreed
      were asked why they did not attend their original appointment and what would make
      it easier to attend. Primary reasons for missing appointments included forgetting
      (34%), lacking transportation (36%), and scheduling conflicts (26%). Nearly one
      quarter (24%) stated they could not afford transportation. Findings demonstrate
      transportation is a key barrier to eye care services. Current eye care delivery
      can be improved by addressing barriers to attendance in this context. Alternative
      delivery models should be examined to identify methods for better reaching
      underserved target populations. 

PMID- 23974380
TI  - The impact of parental health literacy on the early intervention referral
      process.
AB  - OBJECTIVE: To compare parents' experience with the early intervention (EI)
      referral process based on health literacy level. METHODS: We interviewed 44
      parents of children referred to EI by their pediatricians. Parents completed the
      Newest Vital Sign (NVS) health literacy assessment. We analyzed transcripts using
      modified grounded theory and compared themes based on health literacy. RESULTS:
      Forty parents completed the NVS. Twenty-eight (70%) had adequate health literacy.
      Four primary themes differed between parents based on health literacy level.
      Parents with low health literacy commonly reported that: (1) they lacked
      continuity with a single pediatrician, (2) they had difficulty contacting EI, (3)
      they were confused about EI or the referral process (4) their pediatricians did
      not explain EI and written materials were not helpful. CONCLUSION: Parents with
      low health literacy commonly reported difficulty with EI referrals including
      contact problems and confusion. Strategies that accommodate parents with low
      health literacy level may improve referral success.

PMID- 23974381
TI  - Doctors and lawyers collaborating to HeLP children--outcomes from a successful
      partnership between professions.
AB  - BACKGROUND: Clear associations exist between socioeconomic risks and health, and
      these risks are often amenable to legal interventions. METHODS: This is a case
      study of an implementation of a medical-legal partnership (MLP) in three
      pediatric primary care centers that serve a predominantly high-risk population.
      Referral circumstances and outcomes over the first three years are described.
      RESULTS: During the three-year study period, 1,808 MLP referrals were made for
      1,614 patients by all levels of provider. Those referred were more likely to have
      asthma (p<.0001) and developmental delay/behavioral disorder (p<.0001) than the
      general clinic population. Housing (37%) and income/health benefit (33%) problems
      were the most common reasons for referral. Referrals led to 1,742 (89%) positive
      legal outcomes affecting nearly 6,000 cohabitating children and adults and
      translating into nearly $200,000 in recovered back benefits. CONCLUSION:
      Successful MLP implementation enabled pediatric providers to address social
      determinants of health potentially improving health and reducing disparities.

PMID- 23974382
TI  - "Voicing" the social determinants of health on the backside of a horse racetrack.
AB  - Workers in the horse racing industry often live and work on the backside of the
      track, traveling from track to track as the racing season dictates. There has
      been little research on the social determinants of health and living conditions
      of the workers. We conducted a two-phase project: (1) a cross-sectional survey of
      backside workers; and (2) a community-based participatory research project with
      four workers who worked and lived at a local racetrack using Photovoice.
      Substance abuse, safety concerns, limited access to health care, a high rate of
      work-related injuries and social isolation were common problems reported by the
      workers. Six themes were identified: (1) safety and health; (2) coping; (3) life
      philosophy: fatalism vs. hope; (4) love of horses; (5) working conditions; (6)
      living conditions; and (7) backside culture. Results are discussed in relation to
      the social determinants of health.

PMID- 23974383
TI  - Community perceptions of black infant mortality: a qualitative inquiry.
AB  - Infant mortality is a key public health concern in the United States. Although
      infant mortality rates (IMRs) have declined, the rates among blacks are more than
      twice those of other racial/ethnic groups. Some Florida counties have black IMR
      more than four times the white IMR. The purpose of this study was to explore
      community awareness and perceptions of the rising Black IMR in Gadsden County,
      Florida. Sixty-four black men and women participated in eight focus groups. Data
      were transcribed then analyzed using NVivo 8. Many of the respondents discussed
      issues dealing with access to health care services, trust in providers, and
      perceived differential treatment. Inequities in health care may contribute to a
      culture in which blacks are resistant to seek care thus resulting in poorer
      outcomes. Overall, participants identified awareness and education as the most
      effective ways to address the higher rates of infant mortality among Blacks.

PMID- 23974384
TI  - Recruitment of black and Latina women to a randomized controlled trial.
AB  - BACKGROUND: Minority women are often not adequately represented in randomized
      controlled trials, limiting the generalizability of research trial results.
      METHODS: We implemented a recruitment strategy for a postpartum depression
      prevention trial that utilized patient feedback to identify and understand the
      recruitment barriers of black and Latina postpartum women. Feedback on patients'
      reasons for trial refusal informed adaptations to the recruitment process. We
      calculated weekly recruitment rates and analyzed qualitative and quantitative
      data from patient refusals. RESULTS: Of the 668 women who were approached and
      completed the consent process, 540 enrolled in the trial and 128 declined
      participation. Over 52-weeks of recruitment, refusal rates decreased from 40% to
      19%. A taxonomy of eight reasons for refusal derived from patient responses
      identified barriers to recruitment and generated targeted revisions to the
      recruitment message. CONCLUSIONS: A recruitment strategy designed to incorporate
      and respond to patient feedback improved recruitment of Black and Latina women to
      a clinical trial.

PMID- 23974385
TI  - Black white disparities in receiving a physician recommendation for colorectal
      cancer screening and reasons for not undergoing screening.
AB  - There is consensus that all adults over 50 years of age, regardless of gender,
      race, or ethnicity, should receive a physician recommendation for colorectal
      cancer (CRC) screening. Disparities in CRC screening result in poorer health
      outcomes for blacks than for whites. The purpose of this study was to determine
      whether there are black-white differences in receiving a physician recommendation
      for CRC screening and reasons for undergoing screening. With 12,729 U.S. adults
      ages 50 to 74 included in the analysis, Whites were more likely than blacks to
      report receiving a physician recommendation for CRC screening. Based on age
      adjusted odds ratio, one out of three blacks were less likely to report receiving
      a CRC screening recommendation from their physician (OR=0.68, 95% CI 0.57,0.81).
      This association persisted after adjusting for socioeconomic and other health
      related factors (OR=0.61; 95% CI 0.53,0.71). This study suggests that additional
      steps need to be taken to reduce cancer health disparities.

PMID- 23974387
TI  - Comparison of cancer care and outcomes between a public safety-net hospital and a
      private cancer center.
AB  - We compared the cancer outcomes and care-associated service defects between
      Jackson Memorial Hospital (ABC), a large public safety-net hospital, and
      Sylvester Comprehensive Cancer Center (XYZ), a private not-for-profit cancer
      center in patients with stage II-III colorectal cancer (CC) who received adjuvant
      chemotherapy (AC) and in patients with diffuse large B cell lymphoma (DLBCL).
      Colorectal cancer patients treated at ABC were more likely to have undergone
      urgent surgery. While in the CC cohort, three-year overall survival and relapse
      free survival rates were significantly higher among patients treated at XYZ
      compared with those treated at ABC, there was no significant difference between
      patients treated for DLBCL in the two hospitals. Colorectal cancer patients
      treated at ABC were more likely to have undergone urgent surgery, to have delays
      before surgery or during chemotherapy, and to experience a system/patient-related
      service defect; whereas were less likely to complete a full course of AC. 

PMID- 23974386
TI  - A comparison of colorectal cancer screening uptake among average-risk insured
      American Indian/Alaska Native and white women.
AB  - INTRODUCTION: American Indian and Alaska Native (AI/AN) women have among the
      lowest rates of colorectal cancer (CRC) screening. Whether screening disparities
      persist with equal access to health care is unknown. METHODS: Using
      administrative data from 1996-2007, we compared CRC screening events for 286
      AI/AN and 14,042 White women aged 50 years and older from a health maintenance
      organization in the Pacific Northwest of the U.S. RESULTS: The proportion of
      AI/AN and White women screened for CRC at age 50 was similar (13.3% vs. 14.0%, p
      =.74). No differences were seen in the type of screening test. Time elapsed to
      first screening among AI/AN women who were not screened at age 50 did not differ
      from White women (hazard ratio 1.0, 95% confidence interval 0.8-1.3).
      CONCLUSIONS: Uptake for CRC screening was similar among insured AI/AN and White
      women, suggesting that when access to care is equal, racial disparities in
      screening diminish.

PMID- 23974388
TI  - Genetic counseling, cancer screening, breast cancer characteristics, and general
      health among a diverse population of BRCA genetic testers.
AB  - Outcomes after genetic testing for hereditary breast and ovarian cancer (HBOC)
      syndrome have not been well studied in underserved populations. We surveyed 1,123
      BRCA testers from a genetic counseling program serving an academic cancer center
      (n=1,045) and a public county hospital (n=78) a median of 3.7 years after testing
      for mutations in BRCA1 and BRCA2 (breast cancer susceptibility genes). We
      compared genetic counseling outcomes, cancer screening rates, and self-reported
      general health. We found no differences in genetic counseling outcomes between
      hospitals. Breast cancer screening rates were similarly high at both hospitals,
      which are warranted in this high-risk population. Screening rates for ovarian,
      colon, and skin cancer were significantly lower in participants from the public
      hospital. BRCA results were not a predictor of general health at either hospital.
      When creating a genetic counseling program that serves women in different
      hospital settings, providers should emphasize guidelines-based screening
      recommendations for all patients.

PMID- 23974389
TI  - Circle of Sisters: raising awareness of Native American women to breast cancer.
AB  - The Circle of Sisters is a breast cancer education initiative that incorporates
      free mammography for American Indian women. In two separate but similar
      initiative-sponsored one-day events, 37 American Indian women underwent screening
      mammography and experienced a full day of culturally tailored educational
      activities. Women observed a cooking demonstration, participated in moderate
      exercise activity, strung beads to learn about the dimensions of breast tumors,
      and listened to an American Indian breast cancer survivor recount her story of
      diagnosis and treatment. Significant shifts in opinion included an increase in
      the understanding that a woman's chances of being diagnosed with breast cancer
      increase with age (p=.015) and with never bearing children (p <.001) and that
      breast cancer can be detected early (p=.043). The percentage of those expressing
      an intention to get a mammogram every year grew from 81.1% to 94.6%. 

PMID- 23974390
TI  - Do hospitals that serve a high percentage of Medicaid patients perform well on
      evidence-based guidelines for colon cancer care?
AB  - BACKGROUND: Previous work suggests hospitals serving high percentages of patients
      with Medicaid are associated with worse colon cancer survival. It is unclear if
      practice patterns in these settings explain differential outcomes. HYPOTHESIS:
      High Medicaid hospitals (HMH) have lower compliance with evidence-based care
      processes (examining 12 or more lymph nodes (LN) during surgical staging and
      providing appropriate chemo-therapy). METHODS: Retrospective analysis of stage I
      III colon cancers from California Cancer Registry (1996-2006) linked to discharge
      abstracts and hospital profiles predicted hospital compliance with guidelines and
      trends in compliance over time. RESULTS: Cases (N=60,000) in 439 hospitals
      analyzed. High Medicaid hospital settings had lower odds of compliance with the
      12 LN exam (OR(HMH)0.91, CI(HMH)[0.85, 0.98]) and with the delivery of
      appropriate chemotherapy (OR(HMH)0.76, CI(HMH)[0.67, 0.86]). CONCLUSIONS: High
      Medicaid hospital status is associated with poor performance on evidence-based
      colon cancer care. Policies to improve the quality of colon cancer care should
      target these settings.

PMID- 23974391
TI  - Systematic review of school-based obesity interventions targeting African
      American and Hispanic children.
AB  - PURPOSE: Minority groups are disproportionally affected by the obesity epidemic.
      Schools represent an environment conducive to targeting obesogenic risk factors.
      The purpose of this review was to analyze systematically school-based
      interventions targeting African American and Hispanic children. METHODS:
      Inclusion criteria were: completed experimental and quasi-experimental
      interventions targeting African American or Hispanic children in school settings
      located in the United States. RESULTS: A total of 10 articles met the specified
      inclusion criteria. Programs that affected body composition included physical
      activity and nutritional modalities and three of the programs modified school
      meals. Eight of the interventions incorporated behavioral theory as the framework
      for the intervention; however, only two programs explicitly operationalized the
      theories employed. DISCUSSION: Efficacy of school-based interventions targeting
      minorities can be enhanced through explicit operationalization of behavioral
      theories, incorporation of systematic process evaluation, long-term follow-up of
      intervention outcomes, and inclusion of the family and home environment.

PMID- 23974392
TI  - HIV, tobacco use, and poverty: a potential cause of disparities in health status
      by race and socioeconomic status.
AB  - Tobacco use in the U.S. has declined significantly since the 1960s, but
      differentially by socioeconomic status. Current HIV (human immunodeficiency
      virus) infection rates in the United States are higher in minorities and
      underprivileged individuals. Effective highly active anti-retroviral therapy
      (HAART) has changed HIV into a chronic infection. Mortality among HIV patients is
      now as likely to be due to heart disease and cancers as HIV-related infections.
      In the current situation, one would expect public insurance plans to focus on
      interventions targeting lifestyle-associated behaviors such as tobacco use that
      have been found to be associated with increased risk for heart disease and
      cancers. Review of the AIDS Drug Assistance Program formularies and the Medicaid
      Programs of 50 states and the District of Columbia, however, revealed that
      coverage for smoking cessation is inadequate in most instances. To reduce health
      disparities, publicly funded programs that serve the nation's most vulnerable
      should provide coverage for effective tobacco cessation. 

PMID- 23974393
TI  - The triple aims of correctional health: patient safety, population health, and
      human rights.
AB  - Correctional health systems represent some of the largest health systems in the
      United States, caring for patients with high rates of morbidity and mortality.
      The poorly understood realm of correctional health care represents a missed
      opportunity to integrate care for these patients with care provided by community
      health providers. Three aims are integral to effective correctional health:
      patient safety, population health, and human rights. Patient safety and
      population health are well-defined aims in community health care systems and
      emerging in correctional settings. Dual loyalty and other unique challenges in
      correctional settings make the human rights aim absolutely essential for
      promoting correctional health. 

PMID- 23974395
TI  - The effect of educational attainment on HIV testing among African Americans.
AB  - A person is infected with human immunodeficiency virus (HIV) every nine and half
      minutes in the United States. Moreover, one in five people infected with HIV in
      the United States does not know their status. While African Americans make up
      just 14% of the United States population, they constitute 44% of new HIV
      infections each year in the United States.4 This study examined the relationship
      between level of education and HIV testing among African Americans. A sample of
      3,254 African American men and women between 18-84 years of age was isolated from
      the 2008 National Health Interview Survey and analyzed. The results revealed that
      African Americans with greater educational attainment (high school diploma or
      greater) are more likely to report having been tested for HIV than those who have
      not graduated from high school.

PMID- 23974394
TI  - The development and evaluation of a compassion scale.
AB  - Compassion is the capacity for being moved by suffering of others and wanting to
      help alleviate it. Compassion may mediate health benefits and hazards of social
      networks/relationships. The monitoring/management of level of compassion across
      social networks/relationships may be critical to health benefits' preservation
      and social networks/relationships' health hazards prevention. We developed and
      evaluated the psychometric properties of 10-item self-report measure of
      compassion among 310 respondents from the University and surrounding communities.
      The mean total score was 3.62 (SD=1.09). The item-to-total correlations ranged
      from 0.50-0.71. The mean inter-item correlation was 0.33. The internal
      consistency was 0.82. The scale correlated well with Sprecher and Fehr's
      Compassionate Love Scale (r=0.66; p=.000). Two factors measuring same construct
      explained 57% of sample variance. The scale is user-friendly, easy to score, and
      characterized by good psychometric properties. It can be used to foster
      understanding of the impact of compassion on disease and outcomes across social
      networks/relationships. 

PMID- 23974396
TI  - Gender, race, pain, and subjective well-being of adults with spinal cord injury.
AB  - OBJECTIVE: Assess the relationship of race and gender with subjective well-being
      (SWB) and determine if pain severity and pain interference mediated that
      relationship. DESIGN: Cross-sectional study of 2,416 people with traumatic SCI.
      Subjective well-being (home life, vocational, and global) was measured by the
      Life Situation Questionnaire. RESULTS: Pain severity and pain interference were
      significantly correlated with each SWB domain. Race was initially significantly
      associated with home life and vocational SWB. Blacks were more likely to report
      lower scores on home life and vocational SWB than whites. After accounting for
      pain severity and pain interference, race was still associated with vocational
      and home life SWB. Gender differences were seen in relation to vocational SWB,
      even after controlling for pain severity and interference. CONCLUSIONS: Pain
      severity and pain interference only partially mediated SWB. Gender and race were
      associated with lower vocational SWB. Future research should assess potential
      explanations for this disparity.

PMID- 23974397
TI  - Perceptions of harm to health from cigarettes, blunts, and marijuana among young
      adult African American men.
AB  - OBJECTIVES: To assess perceptions and knowledge of health effects of smoking
      tobacco, blunts, and marijuana among adult African American (AA) men aged 19-30
      in five Black Belt counties of rural Alabama. METHODS: Cross-sectional study
      using interviewer-administered oral surveys. RESULTS: Four hundred and fifteen
      participants completed surveys. Cigarettes were the most common initial and
      current product used (40%) and there were more current than initial users of
      marijuana and blunts. Significantly more cigarette users (80%) felt that smoking
      cigarettes was harmful to health compared with marijuana (33%) and blunt (53%)
      users (p < .001). Many marijuana smokers (71%) and blunt smokers (48%) believed
      smoking their product was safer than cigarettes for reasons including more
      natural and less addictive. CONCLUSIONS: When compared with cigarettes, knowledge
      of the health-related effects of smoking marijuana-containing products among
      young African American men is poor. Intervention strategies focusing on the
      adverse health effects of smoking marijuana are needed.

PMID- 23974398
TI  - Infant mortality in American Indians and Alaska Natives 1995-1999 and 2000-2004.
AB  - OBJECTIVES: (1) To determine the infant mortality rate (IMR) in American
      Indians/Alaska Natives (AI/AN) and whites between 1995-1999 and 2000-2004. (2) To
      compare the leading causes of infant mortality in AI/AN and whites. (3) To
      examine differences in neonatal vs. postneonatal causes of death in whites and
      AI/AN. METHODS: Using the 1995-99 and 2000-04 Centers for Disease Control and
      Prevention's National Center for Health Statistics national linked birth/infant
      death data, we examined neonatal and post-neonatal IMR among AI/AN and whites.
      RESULTS: AI/AN experienced significantly greater overall IMR in 1995-1999 and
      2000-2004 than whites. While the reduction in the IMR between these time periods
      was statistically significant for whites, the reduction among AI/AN was not. We
      found that AI/AN had an IMR 1.5 times as high as that of whites. CONCLUSIONS:
      While the overall IMR has decreased in AI/AN, disparities in postneonatal IMR
      persist between AI/AN and Whites.

PMID- 23974399
TI  - Decision-making processes of patients who use the emergency department for
      primary care needs.
AB  - Emergency department (ED) use for non-urgent needs is widely viewed as a
      contributor to various health care system flaws and inefficiencies. There are few
      qualitative studies designed to explore the complexity of patients' decision
      making process to use the ED vs. primary care alternatives. In this study, semi
      structured interviews were conducted with 30 patients who were discharged from
      the low acuity area of a university hospital ED. A grounded theory approach
      including cycles of immersion/crystallization was used to identify themes and
      reportable interpretations. Patients reported multiple decision-making
      considerations that hinged on whether or not they knew about primary care
      options. A model is developed depicting the complexity and variation in patients'
      decision-making to use the ED. Optimizing health system navigation and use
      requires improving objective factors such as access and costs as well as
      subjective perceptions of patients' health care, which are also a prominent part
      of their decision-making process. 

PMID- 23974400
TI  - Urban, low-income, African American light smokers: perceptions of cessation
      counseling.
AB  - Nine focus groups (N = 57), which included a demographic survey, were conducted
      to evaluate urban, low-income, African American light smokers' experiences of
      cessation counseling. Chi-squared and independent t-tests were run to analyze
      survey data. Participants with a self-reported co-morbidity were more likely than
      participants without a co-morbidity to have been asked about quitting, and
      advised to quit. Fewer than half of all participants reported recommendations to
      use cessation pharmacotherapy, try a quit smoking program, or have a follow-up.
      Qualitative analysis revealed three focus group themes: (1) health provider as
      information source; (2) unsatisfactory counseling; and (3) mistrust of physician
      prescribed pharmacotherapy. Participants expressed frustration regarding
      receiving inadequate counseling for smoking cessation since they viewed health
      providers as the most trusted source for health information. Findings demonstrate
      the need for further study of cessation counseling among urban, low-income,
      African American light smokers, particularly those with co-morbidities. 

PMID- 23974401
TI  - Does the association between prescription copayment increases and medication
      adherence differ by race?
AB  - Previous studies have shown prescription copayment increases are associated with
      decreases in adherence to diabetes and hypertension medications, but have not
      investigated whether these associations differ by race. Veterans Affairs (VA)
      administrative data were used to analyze medication adherence before and after an
      increase in prescription copayments from $2 to $7 for a 30-day supply in February
      2002. Applying a difference-in-difference approach, we compared adherence changes
      among White and Black veterans who were exempt from or required to pay medication
      copayments. The likelihood patients were adherent to diabetes or hypertension
      medications decreased after the copayment increase for both White and Black
      veterans. However, differences in medication adherence reductions between White
      and Black veterans were small and statistically insignificant. Despite barriers
      faced by minority patients related to lower perceived value of medications, the
      impact of a copayment increase on adherence was similar across the two largest
      racial groups in the VA. 

PMID- 23974402
TI  - Medical home disparities are not created equal: differences in the medical home
      for children from different vulnerable groups.
AB  - OBJECTIVE: To identify components of the medical home that contribute to medical
      home disparities for vulnerable children. METHODS: Cross-sectional analysis of
      2007 National Survey of Children's Health. Prevalence of components of the
      medical home were estimated by special health care needs (SHCN), race/ethnicity,
      primary language, and health insurance. RESULTS: Medical home disparities for
      children with SHCN were driven by differences in getting help with care
      coordination, when needed (71% vs. 91% children without SHCN, p<.001). Medical
      home disparities for other groups were largely attributable to less family
      centered care (Hispanic 49% and African American 55% vs. White 77%, p<.001; non
      English primary language 37% vs. English 72%, p<.001; uninsured 45% and publicly
      insured 57% vs. privately insured 75%, p<.001). CONCLUSIONS: The components of
      the medical home that contribute to medical home disparities differ between
      groups of vulnerable children. Medical home implementation may benefit from
      focusing on the specific needs of target populations.

PMID- 23974403
TI  - Serving homeless veterans in the VA Desert Pacific Healthcare Network: a needs
      assessment to inform quality improvement endeavors.
AB  - This report describes a needs assessment of VA programs for homeless Veterans in
      Southern California and Nevada, the geographic region with the most homeless
      Veterans in the nation. The assessment was formulated through key informant
      interviews. Current service provisions are discussed, along with salient unmet
      needs for this vulnerable population. 

PMID- 23974404
TI  - Effect of race and health insurance on health disparities: results from the
      National Health Interview Survey 2010.
AB  - Significant race-related disparities persist in the U.S. regarding access to
      health services. Initiatives to reduce such disparities have often focused on
      expanding health insurance coverage for vulnerable populations. Based on our
      analysis of 2010 data from the National Health Interview Survey, we found that
      race is a much greater factor than insurance status in accounting for disparities
      in access to health services. Expanding health insurance through reform
      initiatives such as the Patient Protection and Affordable Care Act may have
      relatively little impact on reducing racial and ethnic disparities in the US. 

PMID- 23974405
TI  - An academic, business, and community alliance to promote evidence-based public
      health policy: the case of primary seat belt legislation.
AB  - An academic, business, and community alliance comprising 285 organizations,
      including 43 national groups represented on a Blue Ribbon Panel organized by the
      U.S. Secretary of Transportation, targeted Arkansas, Florida, Mississippi,
      Minnesota, Tennessee, and Wisconsin for high involvement/intervention consisting
      of community organization and other political action to support passage of
      primary seat belt laws. State-level alliance activities began in January 2003.
      All six states enacted a primary seat belt law between 2004 and 2009. From
      January 2003 to May 2010, passage of primary legislation was 4.5 times as likely
      (95% CI 1.90, 10.68) in states with high versus low alliance involvement.
      Positive interaction between high alliance involvement and offers of federal
      incentives may have occurred as well. This evidence of success suggests that
      academic-business-community alliances for action to promote evidence-based public
      health policy may be effective. 

PMID- 23974406
TI  - Ghana's National Health Insurance Scheme: insights from members, administrators
      and health care providers.
AB  - The Ghana National Health Insurance Scheme (NHIS) was established as part of a
      poverty reduction strategy to make health care more affordable to Ghanaians. It
      is envisaged that it will eventually replace the existing cash-and-carry system.
      This paper examines the views of NHIS administrators, members/enrollees, and
      health care providers on how the Scheme operates in practice. It is part of a
      larger evaluation project on Ghana's NHIS, sponsored by the Bill and Melinda
      Gates Foundation and the Global Development Network as part of a two-year global
      research. We rely primarily on qualitative data from focus group discussion in
      the Brong Ahafo and the Upper East regions respectively. Our findings suggest
      that the NHIS has improved access to affordable health care services and
      prescription drugs to many people in Ghana. However, there are concerns about
      fraud and corruption that must be addressed if the Scheme is to be financially
      viable. 

PMID- 23974407
TI  - Losing work: regional unemployment and its effect on homeless demographic
      characteristics, needs, and health care.
AB  - BACKGROUND: Who becomes homeless because of unemployment and what they need are
      poorly understood. METHODS: Four-year time-series study. Homeless
      characteristics, co-morbid conditions, and needs are correlated with unemployment
      rates. RESULTS: The unemployment rate averaged 6.7% during years 1-2 (N=198) and
      11.8% during years 3-4 (N=202). Those presenting during high unemployment worked
      most recently in clerical positions (10.4% vs. 4.5%, p= .02) and reported
      unemployment (OR=2.0; 95% CI; 1.07, 3.76) and unaffordable housing (28.7% vs.
      15.2%; p<.01) causing homelessness. Those reporting unemployment were more likely
      to be local residents (OR=2.1; CI=1.01, 4.53), but less likely to have family
      support (OR=0.4; CI=0.19, 0.87). While comparable proportions reported mental
      health conditions and received care, more high unemployment individuals reported
      needing additional care (59.9% vs. 42.9%; p<.001) and that this was necessary for
      leaving homelessness (58.9% vs. 44.1%; p=.05). CONCLUSIONS: High unemployment
      expands the population vulnerable to homelessness and influences health care
      needs and social needs.

PMID- 23974409
TI  - Note from the editor.

PMID- 23974410
TI  - Application of sildenafil for pulmonary hypertension in canines and foals.
AB  - Pulmonary arterial hypertension is the most commonly recognized form of pulmonary
      hypertension in canines. Persistent pulmonary hypertension is a life-threatening
      condition in neonatal foals. Treatment of pulmonary hypertension in both canines
      and neonatal foals has focused on the correction of hypoxia and acidosis, not on
      the pulmonary hypertension itself. Identification of pulmonary hypertension in
      canines and foals has been made easier with the new diagnostic technologies that
      are being employed by veterinarians. Although retrospective reviews and studies
      have been published on the use of sildenafil, which is used primarily for the
      treatment of human erectile dysfunction, to treat pulmonary hypertension in human
      neonates, and the pharmacodynamics of sildenafil have been examined in various
      species, sildenafil has not been used widely in dogs or foals. Therefore, the
      adverse effects of sildenafil in canines and foals have not been determined.
      Until the stability of sildenafil in suspension has been determined, it is
      recommended that dose-specific capsules be prepared by compounding pharmacists
      utilizing lactose as a diluent and that veterinarians be encouraged to prescribe
      small quantities of capsules until a maintenance dose has been achieved. 

PMID- 23974411
TI  - Compounding for feline herpetic keratitis.
AB  - Feline herpetic keratitis (infectious keratoconjunctivitis), an infection of the
      conjunctiva and cornea that is common in cats, involves a three-pronged treatment
      approach: (1)antiviral therapy, (2)immunomodulatory therapy, and (3)antibacterial
      therapy. Since very few agents have been approved for the treatment of feline
      herpetic keratitis, and many of the drugs that were approved at one time for this
      indication can no longer be purchased, compounding pharmacists can play a vital
      role in the prevention and treatment of this infection. Investigators at the
      Colorado State University College of Veterinary Medicine and Biomedical Science
      evaluated the effect of a new antiviral agent, cidofovir, for ophthalmic use in
      treating feline herpetic keratitis. Researchers concluded that application of
      cidofovir significatnly decreased the clinical signs of acute ocular infection in
      cats with feline herpesvirus type 1, one of the primary causes of feline herpetic
      keratitis. Working with veterinary ophthamologists, compounding pharmacists can
      develop other treatment options in patient-speciic dosages and dosage forms to
      ensure that treated cats have an excellent response to therapy. 

PMID- 23974412
TI  - Compounding for veterinary medicine.
AB  - As challenging as it can sometimes be to determine appropriate forms of medicines
      that assure compliance by humans, doing so for veterinary patients is even more
      challenging. Most human patients can communicate their preferences and
      tolerances; for example, those with swallowing problems can report their
      difficulties with oral dosage forms, and most children react unmistakably to
      unpalatable flavors or the prospect of an injection. Animal patients, however,
      must communicate by way of their behovioral reactions to a dosage form, as their
      verbalization capabilities are limited to their species. Dosing veterinary
      patients requires imagination and ingenuity from a compounding pharmacist. This
      brief summary, along with the featured case report, examines some of the
      challenges that veterinary compounding pharmacists face. 

PMID- 23974413
TI  - Taurine for the Treatment of Canine Dilated Cardiomyopathy: A Veterinarian's
      Personal Experience.
AB  - In dogs, dilated cardiomyopathy is a common cardiac disease that is associated
      with treatment failure, a progressively compromised quality of life, and eventual
      death from heart failure. Cardiomyopathy in companion animals is treated with a
      variety of drugs manufactured for the management of cardiac dyfunction in humans,
      but often those agents do not produce a significantly beneficial response in
      veterinary patients. In this article, Lara Ivan, DVM, presents her personal
      experience with the use of a compounded form of the amino acid taurine in the
      treatment of her Doberman pinscher, whose dilated cardiomyopathy was
      characteristically sudden in onset. Robert Borger, RPh, a specialist in
      veterinary compounding, comments on the preparation of taurine for use in dogs
      with dilated cardiomyopathy. 

PMID- 23974414
TI  - Case report: treatment of canine colitis in a dachshund with a compounded oral
      tri-mix (green lizard).

PMID- 23974415
TI  - Biobullet: innovative pharmaceutical compounding for treating cattle.
AB  - Large animals in herds are susceptible to illnesses related to proximity as well
      as to the stress of captivity. Thanks to innovative veterinarians and
      pharmacists, pharmaceutical technology has entered a new phase in delivery
      systems for medications and vaccines to large animals. An advanced method of
      administering prescription drugs in a manner that has dramaticaly reduced the
      stress of those who administer the drugs, as well as the veterinary patients
      receiving the drugs, is the Biobullet, a ballistic bullet with a core of
      antibiotic. This patented dosage form, which was developed by SolidTech Animal
      Health, Inc., located in Newcastle, Oklahoma, is an advanced method of medication
      adminstration that reduces labor costs preventing illness in cattle. As the name
      indicates, the medication is delivered by way of a ballistic system. The doses
      are uniform, premeasured, and require no dilution at the time of administration,
      therefore saving time on the range and eliminating dosage errors and use of
      syringes. This new dosage form has been used experimentally and therapeutically
      in bison, deer, antelope, and stressed zoo animals such as elephants. The
      benefits of this innovative treatment for large veterinary patients is far
      reaching. Considering the strict requirements on medicinal treatments of food
      animals, veterinarians and compounding pharmacists should make the effort to
      learn more about this delivery option. 

PMID- 23974416
TI  - Ronidazole in the treatment of trichomonad infections in cats.
AB  - Tritrichomonas foetus, a microscopic single-celled flagellated protozoan
      parasite, traditionally identified as a cause of reproductive disease in cattle,
      has been demonstrated as an important cause of diarrhea in cats. Until recently,
      an effective antimicrobial treatment for feline Tritrichomonas foetus had not
      been idnetified. Since recommended dosages of antimicrobial drugs have failed in
      cats infected with Tritrichomonas foetus and in vitro studies have revealed
      multiple drug resistance, investigations continue in the effort to find an
      effective treatment. One particular study by Dr.Jody Gookin noted no
      clinicopathological abnormalities or adverse effects with the use of ronidazole,
      and the research concluded that ronidazole administered at 30 to 50 mg/kg orally
      twice daily for 2 weeks was capable of resolving diarrhea and eradicating
      infections of Tritrichomonas foetus in cats. Clinical use of ronidazole has
      revealed a reversible, possibly dose-related, neurotoxicity. Cats receiving
      ronidazole should be monitored for signs of nystagmus, ataxia, or behavior
      change, and ronidazole should be discontinued immediately if any of these signs
      are observed. Many compounding pharmacists have begun stocking pure ronidazole
      powder to prepare veterinarian prescriptions for the treatnment of Tritrichomonas
      foetus. Doses of ronidazole are usually prepared as capsules, the most desirable
      dosage form because (1)the capsules mask the extremely bitter taste of
      ronidazole, (2)exact dosing reduces the risk of neurotoxicity that has been
      reported at higher doses, and (3)the owner can be assured that the entire dose is
      ingested by the cat after administration of a capsule. 

PMID- 23974417
TI  - Equipment, supplies, and facilites required for hospital compounding.
AB  - According to United States Pharmacopeia Chapter 795, the compounding area should
      have adequate space to store and organize all equipment, supplies, and chemicals
      to prevent mix-ups between ingredients, containers, labels, in-process materials,
      and finished preparations, and the area should be arranged in such a manner to
      prevent cross-contamination. Also, there should be adequate space for each
      compounder to safely and efficiently compound each preparation. The ASHP
      Technical Assistance Bulletin on Compounding Non-Sterile Products in Pharmacies
      states that a separate facility is not required for compounding activites. Those
      guidelines state, however, that the compounding area should be isolated from
      potential interruptions, chemical contaminants, and sources of dust and
      particulate matter. Guides to general physical requirements for compounding
      laboratories are easily accessible, and hospital pharmacy administrators should
      make themselves aware of all standards and guidelines for compounding and
      reackaging, because these activities require specialized equipment, supplies, and
      facilites different than those needed by other services of the hospital pharmacy
      department. The large proportion of hospitalized patients who are unable to take
      some commercial drug products and therefore need compounded preparations is
      evidence of the need for an adequate compounding area. 

PMID- 23974418
TI  - Quality-control analytical methods: continuous quality improvement.
AB  - It is vital that all compounding pharmacies have a continuous quality improvement
      program in place by way of standard operating procedures to assure that patients
      receive high-quality preparations. The program should take into consideration any
      federal and state regulatory requirements, as well as professional association
      expectations. Quality control measurements and regular review of those
      measurements are the foundations of a good quality plan. All pharmacy personnel
      should be aware of the importance of reporting potential internal quality
      concerns or problems and should be encouraged to do so without fear of
      repercussions. Ideally, an error-free compounding pracitice would be the goal.
      Since this is not practical, quality issues should not be viewed as problems, but
      as opportunities to improve compounding practices by correcting, before they
      become pervasive, the processes used in the preparation of prescriptions. 

PMID- 23974419
TI  - Basics of compounding for hazardous drugs, part 2: regulation and sources of
      contamination.

PMID- 23974420
TI  - Specialty compounding for improved patient care: a national survey of compounding
      pharmacists.
AB  - The apparent re-emergence of pharmaceutical compounding as an important part of
      health care is largely explained by the increasing demand for pharmaceutical
      preparations that are not commercially available. However, there have been recent
      discussions among regulatory agencies and various stakeholders of the pharmacy
      profession as to the safety and efficacy of pharmaceutical compounding, and how
      compounding should best be regulated. In light of this discussion, the American
      College of Apothecaries conducted a survey of International Journal of
      Pharmaceutical Compounding subscribers in July 2005 to (1) assess the safety and
      efficacy of compounded preparations, (2) describe the types of compounding and
      other professional services that are offered by pharmacists, and (3) describe
      selected compounding pharmacies. In general, respondents reported few incidents
      of adverse events resulting from compounded preparations, and reported having
      offered a variety of compounding, professional, and patient care specialties
      services. 

PMID- 23974422
TI  - PostScription: Challenges Facing an Analytical Laboratory.

PMID- 23974421
TI  - Validation study of the unguator, an apparatus for compounding dermatological
      preparations.
AB  - A study was conducted at the Laboratory of Pharmaceutical Technology, University
      of Liege, Belgium, of the performance of the Unguator Mixing System, an
      instrument belonging to a new generation of electronic mortar and pestle
      apparatus, which was designed to improve pharmaceutical compounding, provide
      pharmaceutically elegant preparations, and reduce nonproductive time. The goal of
      this study was to verify that preparations that met the actual quality criteria
      established by the United States Pharmacopeia, the Therapeutic Compounding
      Formulary, and the British Pharmacopoeia could be achieved by using the Unguator
      Mixing System. To achieve this goal, the optimal conditions, such as speed,
      mixing time, and order of addition of the components, were determined for each of
      several representative preparations. Two different systems were studied, the
      Unguator 2000 and the Unguator E/S, and effectiveness of standard and disposable
      blades was examined. Formulations prepared during the study were tested for
      appearance, microscopic appearance, and, when judged necessary, uniformity of
      content. Study results revealed that both models tested were less suitable for
      preparation of gel bases than for other types bases. Very positive and
      reproducible results were obtained with compositions containing a low content of
      active ingredient in hydrophobic ointment or hydrophilic cream. A hydrophobic
      drug such as clioquinol can be mixed effectively in a hydrophilic carbomer gel
      with either model, as quantitative assays of different batches showed perfect
      homogeneity, and microscopic examination found no large agglomerates. Special
      conditions were required for a material such as benzoyl peroxide which consists
      of large and hard agglomerates. Salicylic acid hydrophobic 10% ointment can be
      prepared without any difficulty with both models. Both systems provided full
      protection for the operator against dust inhalation, since all preparation steps,
      with the exception of weighing the ingredients, occur in closed containers. 

PMID- 23974423
TI  - Antidepressant-like and anxiolytic-like effects of hydrogen sulfide in behavioral
      models of depression and anxiety.
AB  - Depression is a common and debilitating mental illness and is often comorbid with
      anxiety disorders. Altered synaptic plasticity is considered to be an important
      mechanism underlying antidepressant drug action. It has been reported that
      hydrogen sulfide (H2S), the third gaseous transmitter, facilitates the induction
      of hippocampal long-term potentiation and augments synaptic neurotransmission,
      involved in the regulation of synaptic plasticity. The aim of this study was to
      clarify the antidepressant-like and anxiolytic-like effects of H2S. H2S (NaHS,
      1.68 or 5.6 mg/kg, intraperitoneally, for 7 days) exerts a specific
      antidepressant-like effect in the forced swimming test of mice and rats and the
      tail suspension test of mice, and reduces the anxiety-like behaviors of both mice
      and rats in the elevated plus-maze test. These results reveal a unique
      antagonistic action of H2S in depressive-like and anxiety-like behaviors and
      suggest that elevating H2S signaling in the brain may represent a novel approach
      for the treatment of depressive and anxiety disorders. 

PMID- 23974424
TI  - Competing adiabatic and nonadiabatic pathways in the cis-trans photoisomerization
      of cis-1,2-di(1-methyl-2-naphthyl)ethene. A zwitterionic twisted intermediate.
AB  - Identical fluorescence lifetimes and spectra of cis- and trans-1,2-di(1-methyl-2
      naphthyl)ethene reveal an adiabatic cis -> trans photoisomerization pathway that
      accounts for a significant fraction of observed cis -> trans photoisomerization
      quantum yields. The fluorescence quantum yields of both isomers decrease as the
      solvent is changed from methylcyclohexane to the more polarizable toluene or to
      the more polar acetonitrile and there is a corresponding increase in the
      photoisomerization quantum yield in the trans -> cis direction. The pronounced
      solvent dependence of the contribution of the adiabatic pathway to cis -> trans
      photoisomerization--methylcyclohexane (70%), toluene (45%), acetonitrile (31%)-
      is consistent with the participation of a zwitterionic twisted intermediate,
      (1)p*, on the singlet excited state surface which is stabilized as the
      polarizability and/or polarity of the solvent is increased. Solvent stabilization
      of (1)p* favours the nonadiabatic photoisomerization pathways of both isomers and
      diminishes the cis -> trans adiabatic pathway.

PMID- 23974425
TI  - Differences in the sensitivity of pretherapy and post-therapy scans in patients
      undergoing peptide receptor radionuclide therapy.

PMID- 23974427
TI  - HDACIs and the inhibition of invasive potential.
AB  - A major problem in the treatment of cancer and prolongation of patient survival
      is the dissemination of cells from a defined tumor site into a loco-regional
      disease and ultimately to full metastatic spread into distant organs. In the
      manuscript by Ierano et al. multiple chemically diverse histone deacetylase
      inhibitors (HDACIs) in tumor cell types of many diverse origins were shown to
      increase expression of the receptor CXCR4; a receptor whose expression promotes
      metastatic spread of tumor cells and that is correlated with a stage independent
      poor prognosis.(1,2) The ligand of CXCR4, CXCL12, also called stromal cell
      derived factor (SDF1), stimulates signaling through multiple pathways downstream
      of the CXCR4 receptor including SRC kinases, ERK1/2, and STAT3. Inhibition of
      SRC, ERK, or STAT3 can all suppress tumor cell migration and reduce the threshold
      at which tumor cells undergo apoptosis.(3-8) The authors noted that despite
      increased CXCR4 expression following HDACI treatment, exogenous CXCL12 ligand had
      a reduced ability to stimulate cell signaling processes, with the phosphorylation
      of both SRC and STAT3 at activating sites declining. This resulted in less
      induced migration of HDACI-treated tumor cells. No studies were undertaken to
      determine whether HDACI-treated cells transduced to express activated forms of
      SRC or STAT3 or retained their invasive phenotype; however a loss of SRC and
      STAT3 signaling would predict for a less invasive phenotype.

PMID- 23974428
TI  - A novel method for identifying nonlinear gene-environment interactions in case
      control association studies.
AB  - The genetic influences on complex disease traits generally depend on the joint
      effects of multiple genetic variants, environmental factors, as well as their
      interplays. Gene * environment (G * E) interactions play vital roles in
      determining an individual's disease risk, but the underlying genetic machinery is
      poorly understood. Traditional analysis assuming linear relationship between
      genetic and environmental factors, along with their interactions, is commonly
      pursued under the regression-based framework to examine G * E interactions. This
      assumption, however, could be violated due to nonlinear responses of genetic
      variants to environmental stimuli. As an extension to our previous work on
      continuous traits, we proposed a flexible varying-coefficient model for the
      detection of nonlinear G * E interaction with binary disease traits. Varying
      coefficients were approximated by a non-parametric regression function through
      which one can assess the nonlinear response of genetic factors to environmental
      changes. A group of statistical tests were proposed to elucidate various
      mechanisms of G * E interaction. The utility of the proposed method was
      illustrated via simulation and real data analysis with application to type 2
      diabetes.

PMID- 23974429
TI  - Non-exposed endoscopic wall-inversion surgery as a novel partial gastrectomy
      technique.
AB  - In gastric full-thickness resection employing both endoscopy and laparoscopy,
      intraabdominal contamination or even possibly tumor seeding is unavoidable as a
      result of iatrogenic perforation and the resultant spread of gastric juice. To
      minimize contamination and resected tissue volume, we developed a new technique
      without perforation termed non-exposed endoscopic wall-inversion surgery (NEWS),
      and present here the preliminary results. In a clinical observation cohort study,
      NEWS was attempted in six patients with gastric SMT to investigate the procedure,
      mortality, and morbidity. NEWS consists of several steps: marking around a tumor
      on the mucosal as well as the serosal surface, submucosal injection of sodium
      hyaluronate with indigo carmine dye, circumferential seromuscular dissection with
      suture closure under laparoscopy, and circumferential mucosubmucosal incision
      under gastric endoscopy. The resected specimen is then retrieved perorally.
      Perforation occurred as a result of misidentification and technical inadequacy in
      the first three patients. After modification of the devices, the entire procedure
      was successfully achieved in the latter three. There were no complications in any
      of our six cases. NEWS allows en bloc full-thickness resection, theoretically
      avoiding contamination and tumor dissemination into the peritoneal cavity. 

PMID- 23974431
TI  - Lonicera caerulea fruits reduce UVA-induced damage in hairless mice.
AB  - UVA photons are less energetic than UVB photons but they are more abundant in
      solar radiation. Modern tools have shown that UVA light has serious adverse
      effects on the skin. We investigated the effect of consuming Lonicera caerulea
      berries on UVA-induced damage in SKH-1 mice. The mice were fed a diet containing
      L. caerulea berries (10%, w/w) for 14 days before a single UVA (30 J/cm(2))
      treatment. Effects on haematological and antioxidant parameters were evaluated 4
      and 24h after irradiation. The bioavailability of L. caerulea phenolics was also
      assessed. Consuming the L. caerulea berry-enriched diet caused reduced
      malondialdehyde production and increased catalase activity and glutathione levels
      were found in skin and erythrocytes. UVA-induced NADPH:quinone oxidoreductase-1
      and gamma-L-glutamate-L-cysteine ligase protein in skin were reduced in mice fed
      L. caerulea berries. Enhanced heme oxygenase-1 level in skin, interleukin-17 in
      plasma and reduced interleukin-12 levels in plasma were found in the mice on the
      experimental diet. Histological (pyknotic) changes in the nuclei of basal cells
      induced by UVA exposure were reduced in L. caerulea berry consuming animals. HLPC
      MS analysis showed high concentrations of hippuric acid, one of the main
      metabolites of aromatic amino acids and phenolic compounds, in skin, liver, urine
      and faeces of mice consuming the berries. Taken together, consumption of L.
      caerulea berries affords protection from the adverse effects of a single UVA
      exposure mainly via modulation of antioxidant parameters.

PMID- 23974430
TI  - Gender-specific gene-environment interaction in alcohol dependence: the impact of
      daily life events and GABRA2.
AB  - Gender-moderated gene-environment interactions are rarely explored, raising
      concerns about inaccurate specification of etiological models and inferential
      errors. The current study examined the influence of gender, negative and positive
      daily life events, and GABRA2 genotype (SNP rs279871) on alcohol dependence,
      testing two- and three-way interactions between these variables using multi-level
      regression models fit to data from 2,281 White participants in the Collaborative
      Study on the Genetics of Alcoholism. Significant direct effects of variables of
      interest were identified, as well as gender-specific moderation of genetic risk
      on this SNP by social experiences. Higher levels of positive life events were
      protective for men with the high-risk genotype, but not among men with the low
      risk genotype or women, regardless of genotype. Our findings support the
      disinhibition theory of alcohol dependence, suggesting that gender differences in
      social norms, constraints and opportunities, and behavioral undercontrol may
      explain men and women's distinct patterns of association.

PMID- 23974432
TI  - Associations between the major histocompatibility complex class I chain-related
      gene A transmembrane (MICA-TM) polymorphism and susceptibility to psoriasis and
      psoriatic arthritis: a meta-analysis.
AB  - The aim of this study was to assess whether the major histocompatibility complex
      class I chain-related gene A transmembrane (MICA-TM) polymorphism is associated
      with the susceptibility to psoriasis and psoriatic arthritis (PsA). A meta
      analysis was conducted to establish the association between the MICA-TM A9 allele
      and psoriasis and PsA in the general population and each ethnic group. Ten
      studies (6 psoriasis, 4 PsA) involving 2,002 cases and 1,933 controls were
      included in this meta-analysis. The Asian controls showed the lowest A9 allele
      prevalence (16.6%), whereas the European controls had the highest allele
      prevalence (33.3%). Meta-analysis revealed a significant association between the
      MICA-TM A9 allele and the entire study population, which included the psoriasis
      and PsA cases (OR 1.703; 95% CI 1.301-2.229; p = 1.0 * 10(-5)). We further
      divided the entire study population into the psoriasis and PsA groups. Meta
      analysis revealed a significant association between the MICA-TM A9 allele and the
      entire study population (OR 1.427, 95% CI 1.021-1.994; p = 0.037) and Asians (OR
      1.264; 95% CI 1.014-1.576; p = 0.037). A significant association was found
      between the MICA-TM A9 allele and PsA (OR 2.227; 95% CI 1.462-3.393; p = 1.9 *
      10(-5)) and Europeans (OR 2.039; 95% CI 1.285-3.235; p = 0.002). This meta
      analysis showed that the MICA-TM A9 allele is associated with psoriasis
      susceptibility in Asian populations and that the MICA-TM A9 allele is associated
      with a PsA risk in Europeans.

PMID- 23974434
TI  - Visual selective attention in amnestic mild cognitive impairment.
AB  - OBJECTIVES: Subtle deficits in visual selective attention have been found in
      amnestic mild cognitive impairment (aMCI). However, few studies have explored
      performance on visual search paradigms or the Simon task, which are known to be
      sensitive to disease severity in Alzheimer's patients. Furthermore, there is
      limited research investigating how deficiencies can be ameliorated with exogenous
      support (auditory cues). METHOD: Sixteen individuals with aMCI and 14 control
      participants completed 3 experimental tasks that varied in demand and cue
      availability: visual search-alerting, visual search-orienting, and Simon task.
      RESULTS: Visual selective attention was influenced by aMCI, auditory cues, and
      task characteristics. Visual search abilities were relatively consistent across
      groups. The aMCI participants were impaired on the Simon task when working memory
      was required, but conflict resolution was similar to controls. Spatially
      informative orienting cues improved response times, whereas spatially neutral
      alerting cues did not influence performance. Finally, spatially informative
      auditory cues benefited the aMCI group more than controls in the visual search
      task, specifically at the largest array size where orienting demands were
      greatest. DISCUSSION: These findings suggest that individuals with aMCI have
      working memory deficits and subtle deficiencies in orienting attention and rely
      on exogenous information to guide attention.

PMID- 23974433
TI  - Environmental impact on direct neuronal reprogramming in vivo in the adult brain.
AB  - Direct reprogramming of non-neuronal cells to generate new neurons is a promising
      approach to repair damaged brains. Impact of the in vivo environment on neuronal
      reprogramming, however, is poorly understood. Here we show that regional
      differences and injury conditions have significant influence on the efficacy of
      reprogramming and subsequent survival of the newly generated neurons in the adult
      rodent brain. A combination of local exposure to growth factors and retrovirus
      mediated overexpression of the neurogenic transcription factor Neurogenin2 can
      induce new neurons from non-neuronal cells in the adult neocortex and striatum
      where neuronal turnover is otherwise very limited. These two regions respond to
      growth factors and Neurogenin2 differently and instruct new neurons to exhibit
      distinct molecular phenotypes. Moreover, ischaemic insult differentially affects
      differentiation of new neurons in these regions. These results demonstrate strong
      environmental impact on direct neuronal reprogramming in vivo. 

PMID- 23974435
TI  - High performance graphene oxide based rubber composites.
AB  - In this paper, graphene oxide/styrene-butadiene rubber (GO/SBR) composites with
      complete exfoliation of GO sheets were prepared by aqueous-phase mixing of GO
      colloid with SBR latex and a small loading of butadiene-styrene-vinyl-pyridine
      rubber (VPR) latex, followed by their co-coagulation. During co-coagulation, VPR
      not only plays a key role in the prevention of aggregation of GO sheets but also
      acts as an interface-bridge between GO and SBR. The results demonstrated that the
      mechanical properties of the GO/SBR composite with 2.0 vol.% GO is comparable
      with those of the SBR composite reinforced with 13.1 vol.% of carbon black (CB),
      with a low mass density and a good gas barrier ability to boot. The present work
      also showed that GO-silica/SBR composite exhibited outstanding wear resistance
      and low-rolling resistance which make GO-silica/SBR very competitive for the
      green tire application, opening up enormous opportunities to prepare high
      performance rubber composites for future engineering applications. 

PMID- 23974436
TI  - Modeling the binding specificity of the RNA-binding protein GLD-1 suggests a
      function of coding region-located sites in translational repression.
AB  - To understand the function of the hundreds of RNA-binding proteins (RBPs) that
      are encoded in animal genomes it is important to identify their target RNAs.
      Although it is generally accepted that the binding specificity of an RBP is well
      described in terms of the nucleotide sequence of its binding sites, other factors
      such as the structural accessibility of binding sites or their clustering, to
      enable binding of RBP multimers, are also believed to play a role. Here we focus
      on GLD-1, a translational regulator of Caenorhabditis elegans, whose binding
      specificity and targets have been studied with a variety of methods such as CLIP
      (cross-linking and immunoprecipitation), RIP-Chip (microarray measurement of RNAs
      associated with an immunoprecipitated protein), profiling of polysome-associated
      mRNAs and biophysical determination of binding affinities of GLD-1 for short
      nucleotide sequences. We show that a simple biophysical model explains the
      binding of GLD-1 to mRNA targets to a large extent, and that taking into account
      the accessibility of putative target sites significantly improves the prediction
      of GLD-1 binding, particularly due to a more accurate prediction of binding in
      transcript coding regions. Relating GLD-1 binding to translational repression and
      stabilization of its target transcripts we find that binding sites along the
      entire transcripts contribute to functional responses, and that CDS-located sites
      contribute most to translational repression. Finally, biophysical measurements of
      GLD-1 affinity for a small number of oligonucleotides appear to allow an accurate
      reconstruction of the sequence specificity of the protein. This approach can be
      applied to uncover the specificity and function of other RBPs. 

PMID- 23974437
TI  - Ribosome biogenesis requires a highly diverged XRN family 5'->3' exoribonuclease
      for rRNA processing in Trypanosoma brucei.
AB  - Although biogenesis of ribosomes is a crucial process in all organisms and is
      thus well conserved, Trypanosoma brucei ribosome biogenesis, of which maturation
      of rRNAs is an early step, has multiple points of divergence. Our aim was to
      determine whether in the processing of the pre-rRNA precursor molecule, 5'->3'
      exoribonuclease activity in addition to endonucleolytic cleavage is necessary in
      T. brucei as in other organisms. Our approach initiated with the bioinformatic
      identification of a putative 5'->3' exoribonuclease, XRNE, which is highly
      diverged from the XRN2/Rat1 enzyme responsible for rRNA processing in other
      organisms. Tagging this protein in vivo allowed us to classify XRNE as nucleolar
      by indirect immunofluorescence and identify by copurification interacting
      proteins, many of which were ribosomal proteins, ribosome biogenesis proteins,
      and/or RNA processing proteins. To determine whether XRNE plays a role in
      ribosome biogenesis in procyclic form cells, we inducibly depleted the protein by
      RNA interference. This resulted in the generation of aberrant preprocessed 18S
      rRNA and 5' extended 5.8S rRNA, implicating XRNE in rRNA processing. Polysome
      profiles of XRNE-depleted cells demonstrated abnormal features including an
      increase in ribosome small subunit abundance, a decrease in large subunit
      abundance, and defects in polysome assembly. Furthermore, the 5' extended 5.8S
      rRNA in XRNE-depleted cells was observed in the large subunit, monosomes, and
      polysomes in this gradient. Therefore, the function of XRNE in rRNA processing,
      presumably due to exonucleolytic activity very early in ribosome biogenesis, has
      consequences that persist throughout all biogenesis stages. 

PMID- 23974439
TI  - Evaluation of relapse after orthodontic therapy combined with orthognathic
      surgery in the treatment of skeletal class III.
AB  - INTRODUCTION: Multidisciplinary treatment of skeletal malocclusion by
      orthognathic surgery in addition to orthodontics is a routine strategy believed
      to offer good functional and esthetic outcomes. Postoperative relapse is,
      however, a problem. The present study was conducted to analyze the stability of
      outcomes achieved by surgical treatment of skeletal class III patients in terms
      of the rate and extent of relapses. PATIENTS AND METHODS: A total of 30 patients
      who had undergone orthodontic treatment combined with orthognathic surgery were
      included. The primary inclusion criterion was a skeletal class III treated by
      mandibular setback (Obwegeser/Dal Pont) surgery alone or combined with maxillary
      advancement (Le Fort I) surgery. Analysis was based on one preoperative and two
      postoperative cephalograms per patient. RESULTS: We observed relapse (defined, in
      accordance with Proffit, as changes >2 mm or 2 degrees ) at a rate of 24% after
      bimaxillary procedures, compared to a lower rate of 21% after mandibular setback
      procedures only. The relapse rate was 21% among patients who had undergone upper
      jaw surgery versus 27% among those who had undergone lower-jaw surgery, which was
      statistically significant. CONCLUSION: The majority of patients exhibited stable
      treatment outcomes. Maxillary advancement procedures were found to be less
      susceptible to relapse-resulting in more stable outcomes-and mandibular setback
      distances correlated positively with the degree of the relapse. No statistically
      significant differences were observed between the procedures conducted in both
      jaws versus in the lower jaw only, or in the extent of upper-jaw repositioning.

PMID- 23974438
TI  - Identification of neoblast- and regeneration-specific miRNAs in the planarian
      Schmidtea mediterranea.
AB  - In recent years, the planarian Schmidtea mediterranea has emerged as a tractable
      model system to study stem cell biology and regeneration. MicroRNAs are small RNA
      species that control gene expression by modulating translational repression and
      mRNA stability and have been implicated in the regulation of various cellular
      processes. Though recent studies have identified several miRNAs in S.
      mediterranea, their expression in neoblast subpopulations and during regeneration
      has not been examined. Here, we identify several miRNAs whose expression is
      enriched in different neoblast subpopulations and in regenerating tissue at
      different time points in S. mediterranea. Some of these miRNAs were enriched
      within 3 h post-amputation and may, therefore, play a role in wound healing
      and/or neoblast migration. Our results also revealed miRNAs, such as sme-miR-2d
      3p and the sme-miR-124 family, whose expression is enriched in the cephalic
      ganglia, are also expressed in the brain primordium during CNS regeneration.
      These results provide new insight into the potential biological functions of
      miRNAs in neoblasts and regeneration in planarians. 

PMID- 23974440
TI  - Control of lower incisor inclination with a completely customized lingual
      appliance for dentoalveolar compensation of class III malocclusion.
AB  - OBJECTIVE: Bracket slots and orthodontic archwires offering high dimensional
      precision are needed for fully customized lingual appliances. We aimed to
      investigate whether high-precision appliances of this type enable dentoalveolar
      compensation of class III malocclusion so that lower incisor inclination at the
      end of treatment will closely match the anticipated situation as defined in a
      pretreatment setup. MATERIALS AND METHODS: This retrospective study included a
      total of 34 consecutive patients who had worn a fully customized lingual
      appliance to achieve dentoalveolar compensation for class III malocclusion by
      intermaxillary elastics, or proximal enamel reduction, or extraction of teeth in
      one or both jaws. Casts fabricated at different points in time were three
      dimensionally scanned to analyze how precisely the lower incisor inclinations
      envisioned in the setup were implemented in clinical practice. RESULTS: Aside
      from minor deviations of +/-3.75 degrees , the lower incisor inclinations were
      clinically implemented as planned even in patients with major sagittal
      discrepancies. CONCLUSION: Treatment goals predefined in a setup of dentoalveolar
      compensation for class III malocclusion can be very precisely achieved via a
      customized lingual appliance. Correct planning can prevent undesirable lingual
      tipping of the lower incisors. This finding should not encourage a more liberal
      use of dentoalveolar compensation, but it should heighten clinicians' awareness
      of how essential it is to sufficiently consider the individual anatomy of the
      dentoalveolar complex during treatment planning.

PMID- 23974441
TI  - Comparison of three methods to assess individual skeletal maturity.
AB  - BACKGROUND: The knowledge of facial growth and development is fundamental to
      determine the optimal timing for different treatment procedures in the growing
      patient. AIM: To analyze the reproducibility of three methods in assessing
      individual skeletal maturity, and to evaluate any degree of concordance among
      them. DESIGN: In all, 100 growing subjects were enrolled to test three methods:
      the hand-wrist, cervical vertebral maturation (CVM), and medial phalanges of the
      third finger method (MP3). Four operators determined the skeletal maturity of the
      subjects to evaluate the reproducibility of each method. After 30 days the
      operators repeated the analysis to assess the repeatability of each method.
      Finally, one operator examined all subjects' radiographs to detect any
      concordance among the three methods. RESULTS: The weighted kappa values for inter
      operator variability were 0.94, 0.91, and 0.90, for the WRI, CVM, and MP3
      methods, respectively. The weighted kappa values for intra-operator variability
      were 0.92, 0.91, and 0.92, for the WRI, CVM, and MP3 methods, respectively.
      CONCLUSION: The three methods revealed a high degree of repeatability and
      reproducibility. Complete agreement among the three methods was observed in 70%
      of the analyzed samples. The CVM method has the advantage of not necessitating an
      additional radiograph. The MP3 method is a simple and practical alternative as it
      requires only a standard dental x-ray device.

PMID- 23974445
TI  - A 7-year randomized prospective study of a one-step self-etching adhesive in non
      carious cervical lesions. The effect of curing modes and restorative material.

PMID- 23974443
TI  - Effects of air-polishing devices with different abrasives on bovine primary and
      second teeth and deciduous human teeth.
AB  - OBJECTIVE: The present study investigates the effect of air polishing using
      different combinations of devices and abrasive powders on bovine secondary and
      primary dentition and on human deciduous teeth. MATERIALS AND METHODS: Lower
      incisors of freshly slaughtered calves and cows were partially embedded in
      polyurethane and polished flat. Human deciduous incisors and second molars were
      subjected to the same procedure. These various tooth types (bovine secondary,
      bovine primary, human deciduous) were then randomly assigned to 22 groups
      containing 10 teeth each. The specimens in each group were treated by a specific
      combination of an air-polishing device (n=2; PROPHYflex 3(r), Air-Flow(r) Handy
      2+) and an abrasive (n=3; Air-Flow(r) Pulver Classic, ClinProTM Prophy Powder,
      PROPHYpearls(r)) applied from a distance of 5+/-0.5 mm at maximum setting for 60
      s. Additional groups of specimens were polished with CCS(r) 40 or Cleanic(r)
      pastes applied with a rotating brush at low speed. A Perthometer PCV profilometer
      was used to analyze the degrees of surface roughness and enamel reduction in each
      group. RESULTS: PROPHYpearls(r) created significantly (p<0.05; t-test) more
      surface roughness and enamel reduction than both Air-Flow(r) and ClinProTM. There
      was no significant difference between the latter two abrasives. Any surface
      changes created by blasting or polishing were significantly (p<0.05; t-test)
      smaller on the bovine secondary teeth than on bovine primary or human deciduous
      teeth, with no significant difference between the latter two. The degrees of
      surface roughness induced by air polishing surpassed the effect of CCS(r) 40
      paste but resembled the effect of Cleanic(r) paste. CONCLUSION: Both Air-Flow(r)
      Handy 2+ and PROPHYflex 3(r) are appropriate devices to remove plaque and
      discoloration from the surface of deciduous teeth. PROPHYpearls(r) powder is
      excessively aggressive.

PMID- 23974442
TI  - Regulation of macrophage migration and activity by high-mobility group box 1
      protein released from periodontal ligament cells during orthodontically induced
      periodontal repair: an in vitro and in vivo experimental study.
AB  - OBJECTIVE: Recent studies have shown that periodontal ligament (PDL) cells
      interact with macrophages from the immune system during orthodontically induced
      repair of periodontal tissue. Hypothesizing that high-mobility group box 1
      (HMGB1) protein is released by mechanically stressed PDL cells into the
      extracellular space and has a role in mediating the local immune response by
      acting as an "alarmin", this study was performed to further elucidate these
      cellular interactions, with a special focus on the impact of proinflammatory
      mediators secreted by PDL cells on macrophage physiology. MATERIALS AND METHODS:
      The study included an in vivo part in which orthodontic stress was induced in
      rats and their PDL analyzed for expression of HMGB1 by immunohistochemistry after
      5 days of tooth movement. In the in vitro part, human PDL cells were subjected to
      compressive loading, followed by stimulating human macrophages with conditioned
      supernatants of these stressed PDL cells and analyzing how mediators that had
      been released by these cells into the medium would impact macrophage physiology.
      Assays for macrophage migration and osteoclast differentiation were used in
      addition to immunohistochemistry, enzyme-linked immunosorbent assays, and western
      blotting. RESULTS: Induction of mechanical stress was found to upregulate HMGB1
      expression both in vivo and in vitro. At the same time, translocation HMGB1 from
      nuclei into cytoplasm was observed. Culturing macrophages in conditioned PDL cell
      medium was associated with enhanced chemotactic migration and osteoclast
      differentiation. Addition of anti-HMGB1 antibodies to inhibit HMGB1 in the
      conditioned medium was found to significantly attenuate these effects. A less
      marked increase of migration and osteoclast differentiation by macrophages was
      observed after isolated addition of HMGB1, at its observed pathological
      concentration, to nonconditioned medium. CONCLUSION: This study clearly indicates
      an immunomodulatory potential of human PDL cells via release of mediators,
      including HMGB1 protein. Our finding that these mediators modify the migration
      and differentiation of macrophages as a function of periodontal repair during
      orthodontic treatment broadens the theoretical basis toward developing
      interventional strategies to avoid orthodontically induced root resorption.

PMID- 23974446
TI  - Bioenergy from forestry and changes in atmospheric CO2: reconciling single stand
      and landscape level approaches.
AB  - Analyses of global warming impacts from forest bioenergy systems are usually
      conducted either at a single stand level or at a landscape level, yielding
      findings that are sometimes interpreted as contrasting. In this paper, we
      investigate and reconcile the scales at which environmental impact analyses of
      forest bioenergy systems are undertaken. Focusing on the changes caused in
      atmospheric CO2 concentration of forest bioenergy systems characterized by
      different initial states of the forest, we show the features of the analyses at
      different scales and depict the connections between them. Impacts on atmospheric
      CO2 concentration at a single stand level are computed through impulse response
      functions (IRF). Results at a landscape level are elaborated through direct
      application of IRFs to the emission profile, so to account for the fluxes from
      all the stands across time and space. Impacts from fossil CO2 emissions are used
      as a benchmark. At a landscape level, forest bioenergy causes an increase in
      atmospheric CO2 concentration for the first decades that is similar to the impact
      from fossil CO2, but then the dynamics clearly diverge because while the impact
      from fossil CO2 continues to rise that from bioenergy stabilizes at a certain
      level. These results perfectly align with those obtained at a single stand for
      which characterization factors have been developed. In the hypothetical case of a
      sudden cessation of emissions, the change caused in atmospheric CO2 concentration
      from biogenic CO2 emissions reverses within a couple of decades, while that
      caused by fossil CO2 emissions remains considerably higher for centuries. When
      counterfactual aspects like the additional sequestration that would have occurred
      in the forest if not harvested and the theoretical displacement of fossil CO2 are
      included in the analysis, results can widely differ, as the CO2 debt at a
      landscape level ranges from a few years to several centuries (depending on the
      underlying assumptions considered). 

PMID- 23974447
TI  - Environmental analysis of sunflower production with different forms of mineral
      nitrogen fertilizers.
AB  - Environmental profiles of mineral nitrogen fertilizers were used to evaluate the
      environmental disturbances related to their use in cultivation systems in Europe.
      Since the production of mineral fertilizers requires a large amount of energy,
      the present study of bioenergy systems is relevant in order to achieve crop
      yields less dependent on fossil fuels and to reduce the environmental impact due
      to fertilization. In this study, the suitability of the LCA methodology to
      analyze the environmental impact of sunflower cultivation systems with different
      forms of mineral nitrogen fertilizers urea and ammonium nitrate was investigated.
      Effects on climate change were estimated by the use of Ecoinvent 2.2 database
      default value for soil N2O emission factor (1%) and local emission data (0.8%) of
      mineral nitrogen applied to soils. LCA analysis showed a higher impact on
      environmental categories (human health and ecosystem quality) for the system in
      which urea was used as a nitrogen source. Use of urea fertilizer showed a higher
      impact on resource consumption due to fossil fuel consumption. Use of mineral
      nitrogen fertilizers showed a higher environmental burden than other inputs
      required for sunflower cultivation systems under study. Urea and ammonium nitrate
      showed, respectively, a 7.8% and 4.9% reduced impact of N2O as greenhouse gas by
      using direct field data of soil N2O emission factor compared to the default soil
      emission factor of 2006 IPCC Guidelines. Use of ammonium nitrate as mineral
      nitrogen fertilizer in sunflower cultivation would have a lower impact on
      environmental categories considered. Further environmental analysis of available
      technologies for fertilizer production might be also evaluated in order to reduce
      the environmental impacts of each fertilizer. 

PMID- 23974448
TI  - Management options of acquired punctal stenosis.
AB  - Punctal stenosis is a frequent source of patients referral to the otoplasty
      clinic and the search for a procedure that can permanently eliminate epiphora
      without disturbing the normal lacrimal system anatomy and physiology started
      centuries ago and continues today. The following article summarizes the reported
      procedures in the English literature in the acquired punctal stenosis with a
      description of techniques, success rates, and potential complications with the
      goal of identifying the most effective treatment strategy based on the current
      knowledge available. 

PMID- 23974449
TI  - Pigment epithelium-derived factor inhibits high glucose-induced JAK/STAT
      signalling pathway activation in human glomerular mesangial cells.
AB  - OBJECTIVE: To further elucidate the mechanism of the anti-fibrogenic role of
      pigment epithelium-derived factor (PEDF) on diabetic nephropathy. METHODS: Human
      glomerular mesangial cells (HMCs) were treated with 30 mmol/l D-glucose for
      different time intervals (6, 12, 24, and 48 hrs). To examine the beneficial
      effect of PEDF, we incubated the HMCs with high glucose (30 mmol/L) in the
      presence of different concentrations of PEDF (10, 40, and 100 nmol/l) for 24 hrs.
      The study took place in the Laboratory of Endocrinology, Renmin Hospital of Wuhan
      University, Wuhan, China between July 2012 and December 2012. Transforming growth
      factor-beta1 (TGF-beta1) and fibronectin (FN) mRNA was measured by reverse
      transcription-polymerase chain reaction (RT-PCR). The protein synthesis of TGF
      beta1 and FN in the culture medium of HMC was detected by enzyme-linked
      immunosorbent assay. The phosphorylation levels of Janus kinase2 (JAK2) and
      signal transducers and activators of transcription1 (STAT1) were measured using
      western blotting. RESULTS: The exposure of HMCs to 30 mmol/L glucose caused the
      activation of JAK2 and STAT1. It upregulated TGF-beta1 expression and increased
      protein synthesis of FN. These high glucose-induced changes were suppressed by
      PEDF. CONCLUSION: The PEDF can decrease the expression of TGF-beta1 and FN,
      possibly by inhibiting the phosphorylation of JAK/STAT, which may offer a
      promising strategy in the treatment of diabetic nephropathy.

PMID- 23974450
TI  - Performance of chloride/phosphate test in patients with primary
      hyperparathyroidism. Is it related to calcium level?
AB  - OBJECTIVE: To examine the sensitivity of the chloride/phosphate (Cl/PO4) ratio
      with a cut-off point of >33 as a diagnostic test for primary hyperparathyroidism
      (pHPT) in surgically proven patients, and its performance at different calcium
      levels. METHODS: This is a retrospective medical records based study. Data of 120
      patients diagnosed with pHPT, already operated in the Department of Surgery,
      Cisanello Hospital, Pisa, Italy between March 2010 and June 2011 were reviewed.
      They were divided into 4 subgroups according to their calcium levels. The Cl/PO4
      ratio was measured for each patient, with a cut-off point of 33, sensitivity of
      Cl/PO4 test was measured. Test sensitivity was calculated for each subgroup, and
      a correlation with the parathyroid hormone (PTH) level was investigated.
      Performance of the equation was tested for the normocalcemic patients with a
      suitable control group. RESULTS: The sensitivity of Cl/PO4 ratio for the whole
      group was 0.883 (0.809-0.932). The sensitivity was 0.9340 (0.857-0.973) for
      patients with serum calcium above normal levels. A similar result of 0.933 (0.830
      0.978) was demonstrated for the subgroup with hypercalcemia <1 (mg/dL) above
      normal level. Normocalcemic patients constituted 24%; for this subgroup, the
      sensitivity test was 0.724 (0.562-0.887), specificity was 0.763 (0.628-0.898),
      positive predictive value was 0.700 (0.536-0.864), and negative predictive value
      was 0.784 (0.651-0.916). No correlation was identified between the performance of
      formula and serum PTH level. CONCLUSION: The Cl/PO4 test seems to be a good tool
      to anticipate pHPT and showed a fair performance in normocalcemic patients.

PMID- 23974451
TI  - Serum 25-hydroxyvitamin D concentration in patients with psoriasis and rheumatoid
      arthritis and its association with disease activity and serum tumor necrosis
      factor-alpha.
AB  - OBJECTIVE: To assess vitamin D status in psoriasis and rheumatoid arthritis (RA)
      patients and to study whether it was associated with disease activity,
      inflammatory markers, and serum tumor necrosis factor-alpha (TNF-alpha). METHODS:
      This cross-sectional study was conducted at Riyadh National Hospital, Riyadh,
      Saudi Arabia between March and September 2012. It included 43 patients with
      plaque psoriasis, 55 RA patients and 40 healthy controls matched for age. Blood
      samples were drawn from all participants for assessment of 25-hydroxyvitamin D
      [25(OH)D], TNF-alpha, C-reactive protein (CRP), erythrocyte sedimentation rate
      (ESR), parathyroid hormone (PTH), and serum corrected calcium. Disease activity
      of psoriasis and RA were assessed using Psoriasis Area and Severity Index (PASI)
      and Disease Activity Score Index of a 28 joint count (DAS28). RESULTS: We found a
      significant difference between psoriatic patients, RA patients, and healthy
      controls in the mean 25(OH)D (11.74+/-3.60, 15.45+/-6.42, and 24.55+/-11.21
      ng/ml; p=0.000). We found that 25(OH)D was not correlated with PASI, DAS28, TNF
      alpha, CRP, or ESR in psoriatic and RA patients. CONCLUSION: Serum 25-(OH)D
      levels are significantly lower in psoriatic and RA patients than in healthy
      control subjects. Low 25-OHD levels also may provide the rationale for vitamin D
      supplementation in the treatment of psoriasis and RA. More definitive evidence is
      also required to demonstrate the clinical benefit of vitamin D supplementation in
      the treatment of psoriasis and RA.

PMID- 23974452
TI  - Prevalence of vitamin D deficiency in Saudi adults.
AB  - OBJECTIVE: To determine the prevalence of vitamin D deficiency in healthy Saudi
      adults. METHODS: A cross-sectional study carried out as part of the screening and
      early evaluation of kidney disease project. Vitamin D was measured in subjects
      recruited at 2 screening camps in Riyadh, Saudi Arabia, between March to May
      2008. Subjects from the 2 large commercial centers in Riyadh aged >=18 years and
      Saudi nationals were invited. RESULTS: The study sample comprised of 488
      subjects. The mean age of the subjects was 37.43 (11.32) years, of which 50.2%
      (n=245) were males. Twenty-nine percent of subjects were in the vitamin D
      deficiency group, 22.7% were in the relative insufficiency group, and 47.5% had
      normal levels of 25-hydroxy vitamin D. We observed that female gender was an
      independent predictor of vitamin D deficiency or insufficiency (odds ratio [OR]:
      2.992; 95% confidence intervals [CI] 2.069-4.327). Anemia was also a predictor
      for vitamin D deficiency or insufficiency (OR: 3.16; 95% CI 2.02-4.92). Age was
      positively correlated with vitamin D levels (Pearson correlation=0.183, p<0.000).
      CONCLUSION: Vitamin D deficiency is common in healthy Saudi adults. This is more
      pronounced in females and in the younger age groups. Wearing of traditional
      clothes, deliberate avoidance of the sun, and inadequate dietary intake are
      likely to be the principal causes of low vitamin D levels.

PMID- 23974453
TI  - A randomized control trial evaluating the prevalence of obstetrical anal
      sphincter injuries in primigravida in routine versus selective mediolateral
      episiotomy.
AB  - OBJECTIVE: To evaluate the prevalence of obstetrical anal sphincter injuries
      (OASIS), which include third and fourth degree perineal tears in primigravida in
      routine versus selective mediolateral episiotomy. Secondly, to determine the rate
      of episiotomy in local settings. METHODS: This randomized control trial was
      carried out in the labor ward of a tertiary hospital of the Universiti Kebangsaan
      Malaysia Medical Center, Kuala Lumpur, Malaysia between May and October 2009. The
      trial included 171 primigravida beyond 38 weeks gestation who achieved vaginal
      delivery, and randomly assigned to selective and routine episiotomy groups. The
      type of perineal injuries following childbirth among 171 women were evaluated.
      RESULTS: The overall episiotomy rate from both groups was 76.6%. The prevalence
      of third degree perineal tears was 3.7% in the routine compared with selective
      mediolateral episiotomy at 1.1%. There was no occurrence of fourth degree tears
      in both groups. However, selective mediolateral episiotomy was associated with an
      increased risk of periurethral and labial injury compared with the routine group
      (4.5% versus 0%). CONCLUSION: Routine mediolateral episiotomy in primigravida is
      associated with a higher prevalence of obstetrical anal sphincter injuries. As
      anal sphincter injuries are known to have morbidities, selective mediolateral
      episiotomy in primigravida is therefore recommended in the implementation of new
      delivery practice, and in an attempt to reduce our high episiotomy rate.

PMID- 23974454
TI  - Impact of neuromonitoring of recurrent laryngeal nerve and surgical loupes on the
      outcome of thyroidectomy. A retrospective chart review.
AB  - OBJECTIVE: To determine whether the post-operative complication rate of
      thyroidectomy can be reduced using surgical loupes to identify parathyroid gland
      and recurrent laryngeal nerve (RLN) with simultaneous intraoperative
      neuromonitoring of RLN. METHODS: This retrospective chart review was conducted
      from December 2012 to March 2013 at the Ear, Nose, Throat, and Head-Neck
      Department of King Saud Hospital, Riyadh, Kingdom of Saudi Arabia. The study
      group included patients who underwent primary thyroid surgeries performed from
      July 2007 to September 2011, older than 16 years old, without history of vocal
      cord palsy, hypocalcemia, and sternotomy. Patient outcomes were analyzed with
      emphasis on complication rates related to the procedure, operative duration, use
      of drain, and length of hospital stay. RESULTS: Eighty-eight patients underwent
      thyroid surgeries during our study period. Sixty-one underwent total
      thyroidectomy. Temporary hypocalcemia accounted for 14 (15.9%), and permanent
      hypocalcemia accounted for 5 (5.7%) of the patients. None of the patients showed
      vocal cord paralysis, wound infections, or thyroid crisis post-operatively. The
      length of hospital stay was 2-7 days. CONCLUSION: Careful neuromonitoring of the
      RLN nerve using surgical loupes will minimize post-surgical complications,
      decrease hospital stay, and eventually improve surgery outcomes.

PMID- 23974455
TI  - The correlation between gatifloxacin's acute adverse reaction and intravenous
      drip velocity.
AB  - OBJECTIVE: To investigate the correlation between acute adverse reaction (AAR)
      and intravenous drip velocity of gatifloxacin. METHODS: Patients who had received
      intravenous gatifloxacin (0.2g/100 ml) infusion in the Emergency Center, Zhongnan
      Hospital, Wuhan University, Wuhan, China from January to August 2012 were
      enrolled in this study. Patients were randomly divided into 3 groups according to
      different drip velocities: Group A: velocity <=10 drops per minute; Group B: <10
      velocity <=20 drops per minute; Group C: <20 velocity <=30 drops per minute. The
      AAR and demographic data of patients were documented. RESULTS: Acute adverse
      reaction of the skin and digestive system were significantly positively related
      to intravenous drip velocity. The AAR of the cardiovascular system significantly
      increased when the intravenous drip velocity was beyond 20 drops per minute. The
      AAR of nervous system and abnormal glycometabolism has no significant correlation
      with intravenous drip velocity of gatifloxacin. CONCLUSION: Acute adverse
      reactions of skin, digestive system, and cardiovascular system would decrease
      with an appropriate velocity of intravenous gatifloxacin (0.2g/100 ml) less than
      10 drops per minute.

PMID- 23974456
TI  - Socio-demographic determinants of antibiotic misuse in children. A survey from
      the central region of Saudi Arabia.
AB  - OBJECTIVE: To investigate knowledge, beliefs, and practices associated with
      parental antibiotic misuse. METHODS: This cross-sectional study included parents
      visiting 4 malls in Riyadh, Saudi Arabia. The study took place at the College of
      Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia between June and
      December 2010. Self-prescription of antibiotic for a child in the past year was
      defined as antibiotic misuse. RESULTS: From 610 parents (60.5% mothers and 39.5%
      fathers), 11.6% reported self-prescription. Responding parents differed by age,
      education, number of children, and profession. Overall, parents responded that
      antibiotics are required in children with runny nose or cough or sore throat or
      fever (50%); to reduce symptom severity and duration (57.7%), are effective
      against viruses (68.6%), can be stopped on clinical improvement (28.7%), and it
      used by another family member can be used in children (20.1%). Determinants of
      misuse in a multivariable model were income, number of children, type of
      infection treated last year, knowledge of illness requiring antibiotic or being
      unsure, using antibiotics used by an other family member in children, unsure of
      such use, and adjusting for the type of responding parent. CONCLUSION: Parents
      with low income, more than 2 children, lack of knowledge, inappropriate beliefs
      and practices are vulnerable for misusing antibiotics in children.

PMID- 23974457
TI  - Awareness of interventional radiology among final-year medical students and
      medical interns at a university in Southwestern Saudi Arabia.
AB  - OBJECTIVE: To assess the awareness of interventional radiology (IR) among final
      year medical students and medical interns at a Saudi University. Analysis of such
      awareness could help to improve the future of IR in Saudi Arabia. METHODS: This
      cross-sectional study was based on anonymous surveys administered over a one
      month period (1st-31st December 2012). One hundred and nineteen medical students
      and interns of King Khalid University, Abha, Saudi Arabia were included. Forty
      two (35.3%) replies were received. The survey consisted of 25 questions covering
      perception, knowledge, and interest of interventional radiology. RESULTS: The
      majority of the respondents (52%) felt their knowledge in IR is poor. Only 40% of
      the respondents either completed or plan to complete an elective rotation in
      radiology. Thirty-eight percent of respondents were willing to consider a career
      in IR. The most common reason (43%) for not considering a career in IR was lack
      of knowledge. Only 33% correctly identified the route of training of
      interventional radiologist. The majority of respondents thought that
      interventional radiologists performed cardiac angioplasty (81%), and femoral
      popliteal bypass (74%). CONCLUSION: Exposure to IR among medical students and
      interns was poor. This can be addressed by dedicated undergraduate teaching of IR
      by interventional radiologists with emphasis on the clinical practice.

PMID- 23974458
TI  - Clinical effectiveness and influential factors of maxillary rehabilitation with
      zygomatic implant following tumor resection.
AB  - OBJECTIVE: To evaluate the clinical effectiveness and influential factors of
      maxillary rehabilitation with zygomatic implant and prosthesis after tumor
      resection. METHODS: Thirty-six patients with maxillary defects were collected
      prospectively in this study and received zygomatic implant and prosthesis for
      maxillary rehabilitation in the Department of Stomatology of the Municipal
      Hospital, Taizhou, Zhejiang, China from March 2007 to May 2010. The speech
      intelligibility (SI) and masticatory efficiency of pre-rehabilitation and post
      rehabilitation at one, 6, 12, and 24 months were measured. The relationships
      between the following factors (oro-nasal communication, hard-palate resection,
      soft-palate resection, retention teeth) and SI value were analyzed. The
      relationships between the following factors (oro-nasal communication, retention
      teeth, the extent of maxillary defect, tumor recurrence) and absorbance value
      were analyzed. RESULTS: The SI values and absorbance values of post
      rehabilitation at one, 6, 12, and 24 months were higher than that of pre
      rehabilitation values (p<0.05). Linear regression analysis revealed that oro
      nasal communication had a highly significant influence on the SI value of pre
      rehabilitation (p<0.05), while soft-palate resection had a highly significant
      influence on that of post-rehabilitation (p<0.05). Oro-nasal communication had a
      highly significant influence on the absorbance value of pre-rehabilitation
      (p<0.05), while maxillary defect had a highly significant influence on that of
      post-rehabilitation (p<0.05). CONCLUSION: Zygomatic implant and prosthesis
      improved the near and long-term effectiveness of phonetic and masticatory
      function, and elevated life quality of patients with maxillary tumor resection.
      Zygomatic implant and prosthesis are an effective rehabilitation remedy for
      maxillary defects resulting from tumor resection.

PMID- 23974459
TI  - Acceptance of pharmaceutical gifts. Variability by specialty and job rank in a
      Saudi healthcare setting.
AB  - OBJECTIVE: To examine the variability in accepting different types of gifts by
      clinical specialty as well as job rank among physicians working in Saudi Arabia.
      METHODS: This cross-sectional study was carried out between March and July of
      2012 in different regions of Saudi Arabia. A self-administrated questionnaire was
      developed and administered to all participants, both in paper and electronic
      formats. RESULTS: A total of 281 participants answered the question 'do you
      accept pharmaceutical gifts and/or promotions?' Most of the participants (80.1%)
      admitted acceptance of pharmaceutical gifts of any type. The most common gifts
      accepted were free drug samples (58.2%), stationary items such as pens and
      notepads (52.9%), free meals (37.8%), financial support to attend educational
      activities (33.3%), prepaid promotion cards/codes (7.1%), and funding research
      (5.8%).While there were no significant differences in the overall gift acceptance
      by job rank or specialty, there were significant differences in type-specific
      gift acceptance by job rank and specialty. There were some differences in the
      reasons behind gift acceptance by specialty and job rank. CONCLUSION: The results
      of this study indicate that gift acceptance among physicians working in Saudi
      Arabia is common; however, there was no significant differences in the overall
      gift acceptance by job rank or specialty. Nevertheless, there were significant
      differences in type-specific gift acceptance by job rank and specialty.

PMID- 23974460
TI  - Fatal hemophagocytic syndrome as a manifestation of immune reconstitution
      syndrome in a patient with acquired immunodeficiency syndrome.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and potentially life
      threatening condition characterized by uncontrolled hyper inflammation caused by
      various inherited or acquired immune deficiencies. We report a case of a 42-year
      old man, newly diagnosed with HIV on the basis of a low CD4 T lymphocyte count
      (17/mm3) and HIV viral load >100,000 copies/mL by polymerase chain reaction tests
      who was undergoing an anti-retroviral regimen (emitricitabine, tenofovir
      disoproxil fumarate, ritonavir, and darunavir) and opportunistic infection
      prophylaxis (clarithromycin and atovaquone). He was concomitantly diagnosed with
      hemophagocytic syndrome, also known as HLH. He developed increasingly severe
      pancytopenia while on treatment with anti-retroviral drugs.

PMID- 23974461
TI  - The use of porcine derived low molecular weight heparins in Muslims.

PMID- 23974462
TI  - A child with congenital amputation of the foot.

PMID- 23974463
TI  - Warfarin for stroke prevention following anterior ST-elevation myocardial
      infarction.
AB  - OBJECTIVES: To assess the benefit of vitamin K antagonist (VKA) therapy for
      prevention of ischemic stroke following anterior ST-elevation myocardial
      infarction (STEMI) in patients with reduced ejection fraction. METHODS: A
      prospective institutional-based registry was used to identify survivors of
      anterior STEMI with a post-STEMI ejection fraction of 40% or less over a 10-year
      period. Clinical and procedural characteristics were collected from medical
      records and vital status from the Social Security Death Index. Outcomes were
      compared on the basis of VKA use. The primary outcome was a composite of ischemic
      stroke, death, and clinically relevant bleeding. A secondary analysis examined
      the effects of low-molecular-weight heparin bridging therapy. RESULTS: The
      primary outcome occurred in 24.7% (40/162) of VKA patients and 20.5% (22/107) of
      non-VKA patients [adjusted hazard ratio (HR), 1.30; 95% confidence interval (CI),
      0.71-2.31]. Ischemic stroke occurred in 2.5 and 0.9% of VKA patients and non-VKA
      patients, respectively (adjusted HR, 2.81; 95% CI, 0.31-25.1). There was no
      significant difference in the rate of bleeding or death between groups. The
      addition of a low-molecular-weight heparin bridge to VKA therapy was associated
      with increased bleeding events (adjusted HR, 2.55; 95% CI, 1.04-6.24).
      CONCLUSION: Ischemic stroke was infrequent in the 6 months following anterior
      STEMI irrespective of VKA treatment status. The routine use of anticoagulation
      for prevention of stroke following anterior STEMI may not be warranted.

PMID- 23974464
TI  - [Lower limb paresis after total hip arthroplasty. A rare differential diagnosis].
AB  - We report on a case of complex nerve damage during total hip arthroplasty. The
      most severe clinical symptom was proximal leg paresis with diffuse sensory loss.
      There was an extensive causal Iliopsoas hematoma which developed during the
      postoperative rehabilitation under therapeutic anticoagulation for atrial
      fibrillation. An iliopsoas hematoma with subsequent neurological deficits are
      rare events in the field of hip arthroplasty and a literature review is provided.
      The treatment of retroperitoneal hemorrhage is controversial but in most
      instances a conservative approach is favored. The prognosis of neurological
      damage is sobering as only 20 % of victims are expected to achieve complete
      restitution. 

PMID- 23974465
TI  - Impact of different coils on biochemical T2 and T2* relaxation time mapping of
      articular patella cartilage.
AB  - OBJECTIVE: The purpose of our study was to assess T2 and T2* relaxation time
      values of patella cartilage in healthy volunteers using three different coils at
      3.0 Tesla MRI and their influence on the quantitative values. METHODS: Fifteen
      volunteers were examined on the same 3-Tesla MR unit using three different coils:
      (i) a dedicated eight-channel knee phased-array coil; (ii) an eight-channel multi
      purpose coil, and (iii) a one-channel 1H surface coil. T2 and T2* relaxation time
      measurements were prepared by a multi-echo spinecho respectively a gradient-echo
      sequence. A semi-automatic region-of-interest analysis was performed for patella
      cartilage. To allow stratification, a subregional analysis was carried out (deep
      superficial cartilage layer). Statistical analysis-of-variance was performed.
      RESULTS: The mean quantitative T2 values showed statistically significant
      differences in all comparison combinations. The differences between the mean
      quantitative T2* values were slightly less pronounced than the T2 evaluation and
      only the comparison between (i) and (ii) showed a significant difference. The
      results of T2 and T2* values showed, independent of the used coil, higher values
      in the superficial zone compared to the deep zone (p < 0.05). Looking at the
      signal alterations, all coils showed clearly higher values (and thus more signal
      alterations as a sign of noise) in the deep layer. The validation of the
      reliability showed a high intra-class correlation coefficient and hence a very
      high plausibility (ICC was between 0.870 and 0.905 for T2 mapping and between
      0.879 and 0.888 for T2* mapping). CONCLUSIONS: The present results demonstrate
      that biochemical T2 and T2* mapping is significantly dependent on the utilized
      coil.

PMID- 23974466
TI  - Minimum joint space width (mJSW) of patellofemoral joint on standing "skyline"
      radiographs: test-retest reproducibility and comparison with quantitative
      magnetic resonance imaging (qMRI).
AB  - OBJECTIVE: To assess the intraobserver, interobserver, and test-retest
      reproducibility of minimum joint space width (mJSW) measurement of medial and
      lateral patellofemoral joints on standing "skyline" radiographs and to compare
      the mJSW of the patellofemoral joint to the mean cartilage thickness calculated
      by quantitative magnetic resonance imaging (qMRI). MATERIALS AND METHODS: A
      couple of standing "skyline" radiographs of the patellofemoral joints and MRI of
      55 knees of 28 volunteers (18 females, ten males, mean age, 48.5 +/- 16.2 years)
      were obtained on the same day. The mJSW of the patellofemoral joint was manually
      measured and Kellgren and Lawrence grade (KLG) was independently assessed by two
      observers. The mJSW was compared to the mean cartilage thickness of
      patellofemoral joint calculated by qMRI. RESULTS: mJSW of the medial and lateral
      patellofemoral joint showed an excellent intraobserver agreement (interclass
      correlation (ICC) = 0.94 and 0.96), interobserver agreement (ICC = 0.90 and 0.95)
      and test-retest agreement (ICC = 0.92 and 0.96). The mJSW measured on radiographs
      was correlated to mean cartilage thickness calculated by qMRI (r = 0.71, p <
      0.0001 for the medial PFJ and r = 0.81, p < 0.0001 for the lateral PFJ). However,
      there was a lack of concordance between radiographs and qMRI for extreme values
      of joint width and KLG. Radiographs yielded higher joint space measures than qMRI
      in knees with a normal joint space, while qMRI yielded higher joint space
      measures than radiographs in knees with joint space narrowing and higher KLG.
      CONCLUSIONS: Standing "skyline" radiographs are a reproducible tool for measuring
      the mJSW of the patellofemoral joint. The mJSW of the patellofemoral joint on
      radiographs are correlated with, but not concordant with, qMRI measurements.

PMID- 23974467
TI  - Characterization of soft tissue masses: can quantitative diffusion weighted
      imaging reliably distinguish cysts from solid masses?
AB  - OBJECTIVE: To investigate the accuracy of quantitative diffusion-weighted imaging
      (DWI) with apparent diffusion coefficient (ADC) mapping for characterizing soft
      tissue masses (STMs) as cysts or solid masses. MATERIALS AND METHODS: This IRB
      approved retrospective study included 36 subjects with 37 STMs imaged by
      conventional MRI (T1-weighted, T2-weighted, contrast-enhanced T1-weighted
      sequences) and DWI (b-values 50, 400, 800 s/mm(2)) with ADC mapping. STMs were
      defined as non-solid cysts by histology or clinical follow-up, and as solid by
      histology. For each STM, ADC values (range, mean) were recorded by two observers.
      Differences between ADC values in cysts and solid STMs were compared using
      Wilcoxon rank-sum and receiver-operating characteristic (ROC) analysis. RESULTS:
      There were higher minimum (1.65 vs 0.68, p = 0.003) and mean (2.31 vs 1.45, p =
      0.005) ADC values in cysts than solid STMs respectively. Areas under the ROC for
      minimum and mean ADC values were 0.82 and 0.81 respectively. Using threshold ADC
      values of 1.8 (minimum) or 2.5 (mean) yielded a sensitivity of 60 % and 80 %
      respectively, and a specificity of 100 % for classifying a STM as a cyst; for
      tumors with high fluid-signal intensity, the performance of these threshold
      values was maintained. CONCLUSION: Diffusion-weighted imaging with ADC mapping
      provides a non-contrast MRI alternative for the characterization of STMs as cysts
      or solid masses. Threshold ADC values exist that provide 100 % specificity for
      differentiating cysts and solid STMs, even for tumors of high fluid-signal
      intensity on T2-weighted images.

PMID- 23974468
TI  - Os cuboideum secundarium: a rare accessory ossicle with the potential to mimic a
      mass on magnetic resonance imaging.
AB  - Accessory ossicles are common incidental findings on radiographs of the ankle and
      foot. While typically asymptomatic and of no clinical significance, they are
      sometimes associated with local pain or even mistaken for pathological conditions
      such as fractures. Given the potential for misinterpretation, it is important to
      understand their typical locations and appearances. This case highlights an
      exceptionally rare accessory ossicle called the os cuboideum secundarium, located
      adjacent to the cuboid and calcaneus. Interestingly, this case demonstrates the
      potential for this rare ossicle to mimic a mass on magnetic resonance imaging
      (MRI). Furthermore, despite the significant improvements in the understanding of
      musculoskeletal pathology afforded by advancements in cross-sectional imaging
      techniques, this case is a reminder of certain pitfalls that remain. Lastly, it
      highlights the importance of radiographs as an initial diagnostic study in
      evaluating foot pain. 

PMID- 23974470
TI  - Can the NICE "end-of-life premium" be given a coherent ethical justification?
AB  - In 2009 the UK National Institute for Health and Clinical Excellence (NICE)
      announced that its health technology appraisal committees would henceforth give
      special additional weight to health gains from life-extending end-of-life
      treatments. This was a response to mounting concern from NICE's stakeholders that
      effective new drugs for end-stage cancer often fail NICE's standard test of cost
      effectiveness. This change of policy may be justifiable on procedural grounds as
      the result of a democratic political process responding to stakeholder concerns.
      However, according to the "accountability for reasonableness" framework proposed
      by the philosopher Norman Daniels and endorsed by NICE, there also needs to be
      transparency about the substantive ethical grounds for public health care
      resource allocation decisions. In that spirit, I analyze eleven potentially
      relevant justifications for the NICE "end-of-life premium," drawn from the
      economics and philosophy literature: (1) rule of rescue, (2) fair chances, (3) ex
      post willingness to pay, (4) caring externality, (5) financial protection, (6)
      symbolic value, (7) diminishing marginal value of future life years, (8)
      concentration of benefits, (9) dread, (10) time to set your affairs in order, and
      (11) severity of illness. I conclude that none of them yields a coherent ethical
      justification for the NICE end-of-life premium. 

PMID- 23974469
TI  - Failure of propagation of human norovirus in intestinal epithelial cells with
      microvilli grown in three-dimensional cultures.
AB  - Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis.
      Establishment of a cell culture system for in vitro HuNoV growth remains
      challenging. Replication of HuNoVs in human intestinal cell lines (INT-407 and
      Caco-2) that differentiate to produce microvilli in rotation wall vessel (RWV)
      three-dimensional cultures has been reported (Straub et al. in Emerg Infect Dis
      13:396-403, 2007; J Water Health 9:225-240, 2011, and Water Sci Technol 67:863
      868, 2013). We used a similar RWV system, intestinal cell lines, and the same
      (Genogroup [G] I.1) plus additional (GII.4 and GII.12) HuNoV strains to test the
      system's reproducibility and to expand the earlier findings. Apical microvilli
      were observed on the surface of both cell lines by light and electron microscopy.
      However, none of the cell types tested resulted in productive viral replication
      of any of the HuNoV strains, as confirmed by plateau or declining viral RNA
      titers in the supernatants and cell lysates of HuNoV-infected cells, determined
      by real-time reverse transcription PCR. These trends were the same when culture
      supplements were added that have been reported to be effective for replication of
      other fastidious enteric viruses in vitro. Additionally, by confocal microscopy
      and orthoslice analysis, viral capsid proteins were mainly observed above the
      actin filament signals, which suggested that the majority of viral antigens were
      on the cell surface. We conclude that even intestinal cells displaying microvilli
      were not sufficient to support HuNoV replication under the conditions tested. 

PMID- 23974471
TI  - Disinvestments in practice: overcoming resistance to change through a
      sociotechnical approach with local stakeholders.
AB  - For health care, economists have developed cost-effectiveness analysis (CEA) as a
      "rational," analytic tool to set priorities. Attempts to use CEA to decide how to
      cut expenditures, however, have been met with stakeholders' resistance. This
      article presents an illustrative case study of the application of an approach
      explicitly designed to engage stakeholders with conflicting objectives in
      confronting tightening budgets. The outcome of this process, which engaged a
      group of stakeholders including patients, caregivers, clinicians, and managers,
      was a strategy that reconfigured services to produce more health gain at reduced
      total cost. I argue that the key factors that led to overcoming resistance to
      change were (1) the collective character of the deliberations; (2) the analysis
      of the whole pathway; (3) the presence of patients; and (4) the development of a
      model based on CEA principles, which provided a credible rationale for difficult
      decisions. 

PMID- 23974472
TI  - Health care rationing: doing it better in public and private health care systems.
AB  - All public and private health care systems ration patient access to care. The
      private sector rations access to consumers who are willing and able to pay. The
      poor and disadvantaged have limited access to care and inadequate income
      protection. In public health systems, care is provided on the basis of "need,"
      that is, the comparative cost-effectiveness of competing treatments. This results
      in patients being deprived of care if treatments are clinically effective but not
      cost-effective. Rationing health care is ubiquitous. In both types of systems
      physicians have discretion to deviate from these rationing principles. This has
      created inefficient variations in clinical practice. These are difficult to
      resolve because of the lack of transparency of costs and patient outcomes and
      perverse incentives. The failure to remove universal inefficiency in a period of
      economic austerity sharpens awareness of rationing. Hopes of greater efficiency
      are largely faith based. Competing ideologues from the left and the right
      continue to offer evidence for free solutions to long-established problems.
      Inefficiency is unethical, as it deprives potential patients of care from which
      they could benefit. Reducing inefficiency is essential but difficult. The
      universal challenge is to decide who shall live when all will die in a world of
      scarce resources. 

PMID- 23974473
TI  - The Oregon health insurance experiment: when limited policy resources provide
      research opportunities.
AB  - In 2008 Oregon allocated access to its Medicaid expansion program, Oregon Health
      Plan Standard, by drawing names from a waiting list by lottery. The lottery was
      chosen by policy makers and stakeholders as the preferred way to allocate limited
      resources. At the same time, it also gave rise to the Oregon Health Insurance
      Experiment: an unprecedented opportunity to do a randomized evaluation - the gold
      standard in medical and scientific research - of the impact of expanding
      Medicaid. In this article we provide historical context for Oregon's decision to
      conduct a lottery, discuss the importance of randomized controlled designs for
      policy evaluation, and describe some of the practical challenges in successfully
      capitalizing on the research opportunity presented by the Oregon lottery through
      public-academic partnerships. Since policy makers will always face tough choices
      about how to distribute scarce resources, we urge thoughtful consideration of the
      opportunities to incorporate randomization that can substantially improve the
      evidence available to inform policy decisions without compromising policy goals.

PMID- 23974474
TI  - Introduction: evaluation in analytic theory and political practice.
AB  - The development of professional policy analysis was driven by a desire to apply
      "science" to policy decisions, but the vision of apolitical policy analysis is as
      unattainable today as it was at the inception of the field. While there is
      powerful evidence that schemes to "get around" politics are futile, they never
      seem to lose their popularity. The contemporary enthusiasm for health technology
      assessment and comparative-effectiveness research extends these efforts to find
      technical, bureaucratic fixes to the problem of health care costs. As the
      benefits and costs of health care continue to grow, so too will the search for
      analytic evidence and insights. It is important to recognize that the goal of
      these efforts should not be to eliminate but rather to enrich political
      deliberations that govern what societies pay for and get from their health care
      systems. 

PMID- 23974475
TI  - Twenty years of using economic evaluations for drug reimbursement decisions: what
      has been achieved?
AB  - The objective of this article is to examine the impact of economic evaluation on
      the reimbursement process for pharmaceuticals. The changes in the structure of
      reimbursement policies necessary to incorporate economic evaluation have been
      accomplished without major difficulty in most jurisdictions. However, several
      methodological differences in international guidelines for economic evaluation
      exist, only some of which can easily be justified. A number of beneficial changes
      in reimbursement processes have also been observed, such as a trend toward
      requiring the measurement of more meaningful clinical end points and increased
      engagement between manufacturers, drug regulators, and payers. A consistent
      finding in studies of reimbursement decisions is that economic considerations
      have been influential, second only to the strength of the clinical evidence for
      the drug of interest. The impact of economic evaluation on the allocation of
      health care resources is hard to ascertain because little is known about the
      extent to which reimbursement decisions actually lead to changes in health care
      practice. However, there is evidence that economic evaluation has assisted price
      negotiations and enabled reimbursement agencies to target drugs to those patients
      who will benefit the most. 

PMID- 23974476
TI  - Need for appropriate formulations for children: the national institute of child
      health and human development-pediatric formulations initiative, part 1.
AB  - The development and compounding of pharmacotherapeutic formulations that are
      suitable for infants and young children can be a challenging problem. This
      problem results from the lack of knowledge on the acceptability of different
      dosage forms and formulations in children in relation to age and developmental
      status, as well as the lack of reliable documentation of formulations used in
      pediatric clinical trials. As part of its mandate under the Best Pharmaceuticals
      for Children Act to improve pediatric therapeutics, the National Institute of
      Child Health and Human Development has sponsored the Pediatric Formulation
      Initiative. The goal of this ongoing initiative is to address the issues and
      concnerns associated with pediatric therapeutics by convening groups of
      researchers and experts in pediatric formulations from academia, pharmaceutical
      companies, the National Institutes of Health, and the U.S. Food and Drug
      Administration. 

PMID- 23974478
TI  - Pediatric oral formulations: a continual challenge.
AB  - Lack of reliable information and lack of standards are two of the biggest
      obstacles in compounding medications for children. Yet because few medications
      are available commercially in liquid forms appropriate for children, drug
      compounding is essential for these patients. Drug compounding plays an important
      role in ensuring that children receive the medications they need. Compounding
      pharmacists must be vigilant to ensure that the medications they prepare for
      children are based on reliable formulations that use appropriate excipients and
      are consistent in strength and stability. 

PMID- 23974477
TI  - Principles of pediatric palliative care and pain control.
AB  - One of the most difficult challenges in health care today is weighing the burdens
      and benefits of medical treatment. This is especially true in the administration
      of extraordinary treatment to children with cancer and other life-limiting
      illnesses. Cancer is the second-leading cause of death in children and cancer and
      its therapy are associated with any number of symptoms, including pain.

PMID- 23974479
TI  - Sevelamer suspension in children with end-stage renal disease.
AB  - Control of hyperphosphatemia is a major clinical challenge in children with end
      stage renal disease. The best treatment option is a calcium-based phosphate
      binder, but there is evidence that this treatment protocol causes long-term
      complications, including vascular calcification. Sevelamer hydrochloride has been
      shown to be effective in reducing serum phosphorus levels and the calcium
      phosphorus ion product in children on maintenance dialysis and may be key in
      preventing soft-tissue and vascular calcifications in such patients. Until the
      U.S. Food and Drug Administration approves the use of sevelamer hydrochloride in
      children undergoing dialysis and a liquid dosage form becomes available,
      compounding pharmacists will need to prepare this unique compound for these
      patients. 

PMID- 23974480
TI  - Case reports: cocktail dosing in a premature infant with a history of
      cholestasis, seizures, and apnea; treatment of labial adhesions in a child.

PMID- 23974481
TI  - Compounding in crisis: the aftermath of hurricane katrina.
AB  - Hurricane Katrina, which made landfall on August 25, 2005, was probably the most
      costly natural disaster that has occurred in the US. The storm struck
      southeastern Louisiana as a category 3 hurricane with sustained wind speeds of
      125 mph. Storm surge, strong winds, and torrential rain caused extensive
      destruction in Louisiana, Mississippi, Alabama, and Florida, and 80% of New
      Orleans was flooded when breaks developed in the levee system surroundng the
      city. In the aftermath of Katrina, Louisiana pharmacists played a key role in
      aiding the recovery of evacuees and those who could not escape the areas of
      devastation. In this article, the collaboration and contributions of two
      compounding pharmacists (one of whom was also a victim of the hurricane) are
      described, a formulation for the treatment of a local malady is provided, and
      advice for disaster preparedness is presented. 

PMID- 23974482
TI  - Information resources and software for the hospital compounding pharmacist.
AB  - Within the last 20 years, information resources available to compounding
      pharmacists have grown from extremely limited to readily accessible for easy
      retrieval in a timely manner. To provide the best possible compounding service to
      the medical professionals and patients in their community, hospital compounding
      pharmacists should develop good drug information research skills, build and
      maintain a good reference library , and have access to reliable compounding
      resources and medical journals. Compounding information can be found in books;
      journals; online services such as literature search engines, technical support,
      and reference websites; medical libraries; and computer software; other sources
      include professional organizations and networking. Although it can be expensive
      to develop and maintain, an accurate and up-to date compounding information
      resource base is necessary to ensure the quality of hospital compounding
      services. 

PMID- 23974483
TI  - Pychotropic medications in the treatment of feline urine spraying.
AB  - Urine spraying (urine marking) is one of the most prevalent feline behavior
      disorders and a common reason for veterinarian consultation. Although urine
      spraying is a normal feline communication signal, it is unacceptable behavior for
      house cats, and, if untreated can lead to relinquishment, relegation outside, or
      even euthanasia. Urine spraying is associated with a medical disorder in up to
      25% of cats that present for treatment; hence all cats that spray should undego
      clinical examination by a veterinarian to rule out physical causes before a
      psychogenic cause can be presumed. Behavioral treatment involves litter box
      management and medication. A variety of psychotropic medications have proven safe
      and effective for the long-term treatment of psychogenic feline urine spraying,
      but only if they are prescribed appropriately, monitored judiciously, and coupled
      therapeutically with environmental management. The goal of such therapy is to
      reduce the incidence of urine marking to a level acceptable to the owner.
      Compounding pharmacists perform an essential function in modifying doses of
      manufactured anxiolytic and antidepressant medications for use in cats whose
      spraying is psychogenic in origin. In this article, the case is reported of a cat
      successfully treated with psychotropic medication to reduce the incidence of
      urine marking, and medications compounded for that purpose are briefly reviewed.
      The role of the compounding pharmacist in ensuring the success of treatment is
      also discussed. 

PMID- 23974484
TI  - Basics of compounding for hazardous drugs, part 3: safe handling and personal
      protection.

PMID- 23974485
TI  - Quality-control analytical methods: the quality of sterility testing.
AB  - Microbiology, like compounding, is a science that must be demonstrated to show
      that it is reliable, reproducible, and scientifically sound. Aseptic technique
      must become second nature to the microbiologist and the compounding pharmacist.
      With each new drug tested by a quality-control laboratory, there is a
      responsibility that everything possible is done to ensure that the test result
      reported is accurate and reliable. While it is recognized that the conventional
      sterility-testing method has inherent deficiencies, an alternative method cannot
      be used unless it provides equivalent asurance of detecting microbial
      contamination. A quality-control laboratory and compounding pharmacists should
      adhere to the standards of the United States Pharmacopeia when compounding and
      testing preparations. 

PMID- 23974486
TI  - Collaborative drug therapy management and its application to pharmaceutical
      compounding.
AB  - Patient care within the US healthcare system is changing constantly, as are the
      roles of healthcare practitioners, including pharmacists. For over 30 years,
      pharmacists have promoted the concept of clinical pharmacy, which places
      pharmacists in a central role in patient medication management. The goal is to
      allow the pharmacist to become a vital part of treatment planning by
      individualizing patients' therapeutic regimens. The Collaborative Drug Therapy
      Management agreement is a step toward that goal. The combination of drug therapy
      management and compounding pharmacy can be powerful in meeting patients' specific
      needs.

PMID- 23974487
TI  - Pharmacogenomics: The End of Trial-and-Error Medicine?
AB  - "The right dose of the right drug for the right indication for the right patient
      at the right time." In those words, Dr.Felix Frueh captured the essence of
      pharmacogenomics and the goal of all compounding pharmacists. Pharmacogenomics
      provides the tools for prescribing personalized drug therapy that will improve
      treatment outcomes, decrease the incidence of drug-related adverse effects, and
      ultimately reduce the cost of medical care. The use of pharmacogenomics in
      clinical practice is changing as new discoveries make it possible and cost
      effective to identify a patient's unique genetic makeup and apply this
      information to treating medical ailments. With a prescription and the patient's
      pharmacogenomic profile in mind, a compounding pharmacist can prepare a
      customized medication that delivers that patient's unique best dosage in the
      optimal dosage form. 

PMID- 23974488
TI  - Chemical stability of desonide in ear drops.
AB  - The stability of desonide in ear drops was studied by using a stability
      indicating high-performance liquid chromatographic assay method that was
      developed in our laboratory. The concentrations of the drug were directly related
      to peak heights, and the percent relative standard deviation based on five
      injections was 0.5. The products of decomposition and excipients present in the
      dosage forms did not interfere with the developed assay method. The mixture was
      stable for 180 days when stored in amber-colored glass bottles at room
      temperature. The physical appearance of the ear drops remained clear during the
      study period. 

PMID- 23974489
TI  - Physical and chemical stability of palonosetron with metoclopramide and
      promethazine during simulated y-site administration.
AB  - The objective of this study was to evaluate the physical and chemical stability
      of mixtures of undiluted palonosetron hydrochloride 50 micrograms/mL with
      undiluted metoclopramide hydrochloride 5 mg/mL and with promethazine
      hydrochloride 2 mg/mL diluted in 5% dextrose injection during simulated Y-site
      administration. Triplicate test samples were prepared by admixing 7.5 mL of
      palonosetron hydrochloride with 7.5 mL of the undiluted metoclopramide
      hydrochloride and, separately, with the promethazine hydrochloride dilution.
      Physical stability was assessed using a multistep evaluation procedure that
      included both turbidimetric and particulate measurement as well as visual
      inspection. Chemical stability was assessed by using stability-indicating high
      performance liquid chromatographic analytical techniques based on the
      determination of drug concentrations. Evaluations were performed initially upon
      mixing and 1 and 4 hours after mixing. The samples were clear and colorless when
      viewed in normal fluorescent room light and when viewed with a Tyndall beam.
      Measured turbidities remained unchanged; particulate contents were low and
      exhibited little change. High-performance liquid chromatographic analysis
      revealed that palonosetron hydrochloride and both metoclopramide hydrochloride
      and promethazine hydrochloride remained stable throughout the 4-hour test with no
      drug loss. Palonosetron hydrochloride is physically compatible and chemically
      stable with undiluted metoclopramide hydrochloride and also with promethazine
      hydrochloride diluted in 5% dextrose injection during simulated Y-site
      adminstration. 

PMID- 23974490
TI  - Proteome profile of bovine ruminal epithelial tissue based on GeLC-MS/MS.
AB  - The proteome of rumen epithelial tissue was analysed by SDS-PAGE coupled with LC
      MS/MS. 813 non-redundant proteins were identified of which 7.4 % featured
      membrane-spanning domains and 15.4 % harboured a signal peptide. According to the
      gene ontology annotation, the most abundant proteins exhibited binding activities
      related to their molecular functions, were proteins of cellular components or
      belonged to various metabolic processes. A predominant group of canonical
      pathways in the rumen epithelial tissue was identified using the IPA software.
      The GeLC-MS/MS approach was used to characterise the entire protein expression
      repertoire in rumen tissue, providing a more detailed understanding of the
      important biological processes in the rumen.

PMID- 23974491
TI  - Isolation and characterization of a novel epsilon-caprolactam-degrading microbe,
      Acinetobacter calcoaceticus, from industrial wastewater by chemostat-enrichment.
AB  - For the isolation of a epsilon-caprolactam-degrading microbe from wastewaters of
      a factory producing caprolactam, we applied a chemostat-enrichment technique with
      a selective medium containing caprolactam as sole source of carbon and nitrogen.
      This allowed for the isolation of a novel caprolactam-degrading microbe,
      identified as Acinetobacter calcoaceticus. The strain had a critical tolerance of
      19 g caprolactam l(-1) in minimal medium, which is higher than any previously
      reported caprolactam-degrading microbe. A. calcoaceticus also decreased the
      caprolactam content in medium by 65 % within 72 h despite the high caprolactam
      content (10 g l(-1)). This study highlights the potential use of A. calcoaceticus
      strain for the bioremediation of recalcitrant synthetic polymers, such as
      caprolactam.

PMID- 23974492
TI  - Metformin inhibits lung cancer cells proliferation through repressing microRNA
      222.
AB  - Metformin, which is commonly used as an oral anti-hyperglycemic agent of the
      biguanide family, may reduce cancer risk and improve prognosis. However, the
      mechanism by which metformin affects various cancers, including lung cancer,
      remains unknown. MiR-222 induces cell growth and cell cycle progression via
      direct targeting of p27, p57 and PTEN in cancer cells. In the present study, we
      used A549 and NCI-H358 human lung cancer cell lines to study the effects and
      mechanisms of metformin. Metformin treatment reduced expression of miR-222 in
      these cells (p < 0.05). As a result, protein abundance of p27, p57 and PTEN were
      increased in cells exposed to metformin. Therefore, these data provide novel
      evidence for a mechanism that may contribute to the anti-neoplastic effects of
      metformin suggested by recent population studies and justifying further work to
      explore potential roles for it in lung cancer treatment.

PMID- 23974493
TI  - Tissue-specifically regulated site-specific excision of selectable marker genes
      in bivalent insecticidal, genetically-modified rice.
AB  - Marker-free, genetically-modified rice was created by the tissue-specifically
      regulated Cre/loxP system, in which the Cre recombinase gene and hygromycin
      phosphotransferase gene (hpt) were flanked by two directly oriented loxP sites.
      Cre expression was activated by the tissue-specific promoter OsMADS45 in flower
      or napin in seed, resulting in simultaneous excision of the recombinase and
      marker genes. Segregation of T1 progeny was performed to select recombined
      plants. The excision was confirmed by PCR, Southern blot and sequence analyses
      indicating that efficiency varied from 10 to 53 % for OsMADS45 and from 12 to 36
      % for napin. The expression of cry1Ac and vip3A was detected by RT-PCR analysis
      in marker-free transgenic rice. These results suggested that our tissue
      specifically regulated Cre/loxP system could auto-excise marker genes from
      transgenic rice and alleviate public concerns about the security of GM crops.

PMID- 23974494
TI  - Introduction of silent mutations in a codon-optimized xylanase (xynB) results in
      enhanced protein expression in HEK293A cells.
AB  - Xylanase is used extensively to improve feed conversion rates to enhance the
      performance of poultry and pigs. By expressing xylanase in simple-stomached
      animals, new breeds of genetically modified animals with enhanced feed conversion
      rates may be obtained. However, expression of heterologous proteins derived from
      lower organisms in mammalian cells is usually inefficient. When common codons of
      a ''one amino acid-one codon"-optimized xylanase from Streptomyces
      olivaceoviridis were replaced with rare codons, xylanase expression in human
      embryonic kidney 293A cells increased by 1.4- to 2.3-fold as determined by flow
      cytometry, western blot and enzymatic activity assay. Quantitative RT-PCR assay
      indicated that the enhanced expression could not be attributed to altered mRNA
      levels. This study provides an alternative strategy for improving expression
      levels of heterologous proteins in mammalian cells, which is potentially helpful
      for generating genetically modified animals with enhanced feed conversion
      ability. 

PMID- 23974495
TI  - Key regulatory elements of a strong constitutive promoter, P GCW14, from Pichia
      pastoris.
AB  - The promoter of the Pichia pastoris gene GCW14 is strong and constitutive when
      glycerol is the available carbon source. To identify the cis-acting elements of
      this promoter (P GCW14), we constructed expression plasmids where the enhanced
      green fluorescent protein gene was fused to a series of mutants of P GCW14. We
      identified one negative (-114 to -94) and three positive regulatory regions (-426
      to -152, -134 to -114, -94 to -77). The TATA box of P GCW14 was located at -48.
      One negative and four positive regulatory sites were identified combining error
      prone PCR and directed mutation. The mutated promoter, M+20, with an increased
      promoter activity, was then used to express the gene for lipase B from Candida
      antarctica.

PMID- 23974496
TI  - Proteomic analysis of cloned porcine conceptuses during the implantation period.
AB  - Differentially regulated proteins within porcine somatic cell nuclear transfer
      (SCNT)-derived conceptuses were compared with conceptuses that were derived from
      natural matings on day 14 of pregnancy. Proteins that were expressed prominently
      on day 14 were identified in SCNT-derived conceptuses using 2-D PAGE and MALDI
      TOF MS. Sixty eight proteins were identified as being differentially regulated in
      the SCNT-derived conceptuses. Among these, 62 were down-regulated whereas the
      other six proteins were up-regulated. Glycolytic proteins, such as pyruvate
      dehydrogenase, malate dehydrogenase and lactate dehydrogenase, were down
      regulated in the SCNT-derived conceptuses whereas apoptosis-related genes as
      annexin V, Hsp60, and lamin A were up-regulated. Thus, apoptosis-related genes
      are expressed at significantly higher levels in the SCNT-derived conceptuses than
      in the control conceptuses, whereas metabolism-related genes are significantly
      reduced. 

PMID- 23974497
TI  - Attachment of Acidithiobacillus ferrooxidans onto different solid substrates and
      fitting through Langmuir and Freundlich equations.
AB  - Attachments of Acidithiobacillus ferrooxidans ATCC 23270 onto elemental sulfur,
      quartz and complex chalcopyrite were investigated by analysis of its
      extracellular polymeric substances as well as applying Langmuir and Freundlich
      equations. The two equations fitted the adsorption equilibrium data with
      significant correlation coefficient over 0.9. This indicated that bacterial
      attachment is complicated and involves Langmuir and Freundlich characterizations.
      Sulfur-grown cells showed the highest affinity for the three solid substrates.
      The investigated complex chalcopyrite possessed a higher maximum adsorption
      capacity for A. ferrooxidans than elemental sulfur or quartz. The Freundlich
      fitting parameters suggested that quartz had a weaker adsorption capacity and
      smaller adsorption areas than elemental sulfur or the complex chalcopyrite. It is
      not the content of total carbohydrates or proteins in EPS but their ratios that
      determine the affinity differences between cells and substrates. 

PMID- 23974498
TI  - Differentially-expressed genes in Candida albicans exposed to epsilon-poly-L
      lysine.
AB  - Candida albicans is an opportunistic human pathogen whose disinfection is a
      challenge. epsilon-Poly-L-lysine (epsilon-PL), an antagonistic agent, can disrupt
      cell membranes and inhibit the growth of C. albicans. Genes that were
      differentially-expressed in response to epsilon-PL were isolated from C. albicans
      and identified by suppression subtractive hybridization. Ten subtracted clones,
      that share >98 % homology with known genes of C. albicans, were isolated. Among
      these, four genes encoded cell wall-associated proteins. Real-time quantitative
      PCR and northern blot hybridization suggest that these genes are involved in the
      response to epsilon-PL. These findings will help to determine the mechanism of
      the antimicrobial activity of epsilon-PL against C. albicans.

PMID- 23974499
TI  - Evolution and medicine.
AB  - Evolutionary medicine is a new field whose goal is to incorporate an evolutionary
      perspective into medical education, research, and practice. Evolutionary
      biologists and physicians have traditionally been concerned with different
      problems and have developed different ways of approaching and understanding
      biological phenomena. Evolutionary biologists analyze the properties of
      populations and the ways in which populations change over time, while physicians
      focus on the care of their individual patients. Evolutionists are concerned with
      the ultimate causes of biological phenomena, causes that operated during the
      phylogenetic history of a species, while physicians and biomedical scientists
      have been more interested in proximate causes, causes that operate during the
      ontogeny and life of an individual. Evolutionary medicine is based on the belief
      that an integration of these complementary views of biological phenomena will
      improve our understanding of health and disease. This essay reviews the theory of
      evolution by natural selection, as it was developed by Darwin and as it is now
      understood by evolutionary biologists. It emphasizes the importance of variation
      and selection, points out the differences between evolutionary fitness and
      health, and discusses some of the reasons why our evolutionary heritage has left
      us vulnerable to disease. 

PMID- 23974500
TI  - When ethics precludes randomization: put prospective, matched-pair observational
      studies to work.
AB  - Randomized, controlled clinical trials (RCTs) may be possible, permissible, and
      practical in certain circumstances, but ethical or practical considerations often
      preclude their utilization. In many such cases, ethical objections will not apply
      to a similarly oriented, prospective, matched-pair observational study.
      Additionally, if the methodological rigor associated with the RCT is maintained,
      potential epistemic losses due to eliminating randomization will be mitigated. It
      is therefore suggested that when ethics precludes randomization, prospective,
      protocol-driven, matched-pair observational studies be put to work. One can also
      envision extending observational studies beyond their traditional time-dependent
      bounds to encompass never-ending activities focused on the accumulation of
      clinical knowledge in real-world settings. 

PMID- 23974501
TI  - On slicing an obvious salami thinly: science, patent case law, and the fate of
      the early biotech sector in the making of EPO.
AB  - This essay reconstructs in previously unavailable detail the 1980s race to clone
      and market what would be biotechnology's most important product to date,
      erythropoietin or EPO. The scientific contest continued into the U.S. courts,
      which were charged with deciding competing patent claims to the natural substance
      as a drug. Through case law in the new domain of recombinant DNA, the courts
      imposed a de facto policy that shaped the business and scientific environment of
      small biotechnology firms so as to narrow research efforts and assimilate the
      sector to the established pharmaceutical industry. However, alternative
      dispensations in patent law were possible at the time, and the public's interest
      might have been better served. 

PMID- 23974502
TI  - Postmodern medicine: an analysis of the pharmaceutical industry and its critics.
AB  - The relationship between physicians and the pharmaceutical industry has been the
      subject of extensive debate in the last decade or so. This analysis offers some
      personal observations and suggestions on this discussion from the perspective of
      psychiatry. The article analyzes a number of critiques of the pharmaceutical
      industry-the free market myth, the drug price myth, the academic-pharmaceutical
      complex, lack of innovation, ghost authorship, and the profit motive-in relation
      to the ethics of medical practice and suggests some public policy solutions.
      While the focus here is on psychiatry, many of the concepts and principles
      discussed should apply generally to the medical profession as a whole. 

PMID- 23974503
TI  - To repent or to rationalize: three physicians exchange letters on the ethics of
      experimentation in postwar medicine.
AB  - In the late 1990s, three prominent figures of 20th-century medicine-Paul Beeson,
      Howard Burchell, and Shimon Glick-exchanged private letters on the ethics of
      experimentation in the years following World War II. What began as a brief
      published back-and-forth blossomed into a long correspondence filled with humor
      and wisdom even in the face of continued disagreement. The history of postwar
      investigation unfolds memorably in their letters, starting with the
      whistleblowing of Beecher and Pappworth and moving into the 21st century. The
      heart of the discussion focuses on the ethics of consent and legitimate risk in
      clinical investigation, and on the prevalence of violations of patients' rights.
      Glick openly discusses his views about the widespread practice of their
      subjection to experiments without benefit or unrelated to their conditions. In
      opposition, Burchell claims that accusations of ethical misconduct during this
      period were exaggerated, and that most of these studies would pass review boards
      today. Just when things seem to reach an immutable impasse, Beeson weighs in with
      keen insight and personal experience. The debate provides not only an intimate
      perspective on some of the most influential physician investigators of the last
      half-century, but also a context for productively approaching ethical questions
      of today. 

PMID- 23974504
TI  - The rise of pathophysiologic research in the United States: the role of two
      Harvard hospitals.
AB  - Pathophysiologic research, the major approach to understanding and treating
      disease, was created in the 20th century, and two Harvard-affiliated hospitals,
      the Peter Bent Brigham Hospital and Boston City Hospital, played a key role in
      its development. After the Flexner Report of 1910, medical students were assigned
      clinical clerkships in teaching hospitals. Rockefeller-trained Francis Weld
      Peabody, who was committed to investigative, pathophysiologic research, was a
      critical leader in these efforts. At the Brigham, Harvard medical students
      observed patients closely and asked provocative questions about their diseases.
      Additionally, physicians returned from World War I with questions concerning the
      pathophysiology of wartime injuries. At the Boston City Hospital's new Thorndike
      Memorial Laboratory, Peabody fostered investigative question-based research by
      physicians. These physicians expanded pathophysiologic investigation from the
      1920s. Post-war, Watson and Crick's formulation of the structure of DNA led
      shortly to modern molecular biology and new research approaches that are being
      furthered at the Boston Hospitals. 

PMID- 23974505
TI  - Two philosophical deaths: Hume and Hitchens.
AB  - This essay describes the deaths of David Hume (1711-1776) and Christopher
      Hitchens (1949-2012). Both distinguished thinkers and writers, who shared much in
      their world views, died around the same age after a similarly prolonged course of
      terminal illness. However, the great difference in the power of medicine to
      intervene with the goal of cure or preserving life made their lives while facing
      death dramatically different. The narratives of these two deaths help shed light
      on some of the key features that make particular deaths and the processes of
      dying good or bad, as well as highlight the difficulty in achieving a good death
      in the world of contemporary medicine. 

PMID- 23974506
TI  - Medical apps: public and academic perspectives.
AB  - Medical apps have featured in popular websites and mainstream news media in
      recent months. However, there has been almost no mention of these tools in
      journals focusing on relevant ethical or social issues, including conflict of
      interest, the role of politics in science, and technological oversight. This
      essay examines the role that these philosophical issues might play in answering
      both public and academic questions about these pieces of emergent technology. 

PMID- 23974507
TI  - From "does it work?" to "what is 'it'?": implications for voodoo, psychotherapy,
      pop-psychology, regular, and alternative medicine.
AB  - In this article, a "healing method" (HM) is defined as any method intended to
      improve health through non-somatic means. For many healing methods, especially
      within the realm of complementary and alternative medicine (CAM), there is
      mounting debate over the question "Does it work?" Indeed, this seems to be the
      primary question for most stakeholders. Yet in light of the well-documented
      effects of nonspecific factors, particularly empathy and placebo (EP), we contend
      that the basic question is: "What is 'it'?" Without answering this question,
      scientific progress is impossible, and research costs will spiral upwards without
      producing tangible results. Furthermore, it is impossible to characterize the
      potential side effects of healing methods without a full understanding of the
      underlying mechanisms through which they act. It is generally acknowledged that
      many healing methods are sociohistorical artifacts, based on underlying
      theoretical models that are divorced from established science. There is a need
      for healing method research that is accommodating of such methods' fluid nature
      while being congruent with accepted scientific practices. "It works" is no longer
      an adequate justification for any healing method, as "it" often turns out to be a
      combination of nonspecific factors. 

PMID- 23974508
TI  - A theoretical lens for revealing the complexity of chronic care.
AB  - The increasing prevalence of co-occurring multiple chronic conditions in an aging
      population has influenced the debate on complexity in chronic care and nowadays
      provides an impetus to the reform of numerous health systems. This article
      presents a theoretical lens for understanding the complexity of chronic care
      based on research and debate conducted in the context of multiple quality
      improvement programs over the last five years in Belgium and The Netherlands. We
      consider four major components of complexity in chronic care against a background
      of complex adaptive systems: (1) case (patient) complexity; (2) care complexity;
      (3) quality assessment complexity; and (4) health systems complexity. Each of
      these components represents a range of elements that contribute to the picture of
      complexity in chronic care. We emphasize that planning for chronic care requires
      equal attention to the complexity of all four components. It also requires
      multifaceted interventions and implementation strategies that target improvements
      in multiple outcomes related to the structural, process, and outcome components
      of care. Further empirical research is needed to assess the validity of our
      complexity framework in the health-care environment. 

PMID- 23974509
TI  - The logic of medical diagnosis.
AB  - Establishing diagnoses is a crucial aspect of medical practice. However, this
      process has received comparatively little logical and pedagogical attention when
      compared to statistical methods for evaluating evidence. This article
      investigates the logic of medical diagnosis in order to fill this void. It is
      organized in three parts: the first attempts to explain why more attention ought
      to be paid to diagnosis, at least as much as to evidence; the second calls
      attention to the method of diagnosis by abductive reasoning developed in the 19th
      century by Charles Sanders Peirce (1839-1914); and the third demonstrates the use
      and pervasiveness of abduction by any other name in clinical diagnosis. We
      examine six diagnostic strategies in common use that contain most, if not all, of
      Peirce's structure of inquiry in science. 

PMID- 23974510
TI  - Formulating a curriculum on aging and health for university undergraduates.
AB  - There is a need in our society to raise the national consciousness about aging,
      health, and the prospects for longevity, so that many more persons take
      responsibility for their personal health and understand what we will need in an
      era of health-care reform to promote health across the life course. We address
      this imperative by offering a relevant curriculum through a public-health lens,
      designed especially for university undergraduate students. Unlike the traditional
      educational focus on graduate students who are already committed to a career in
      the health professions, the students in our sights have little prior exposure to
      the course content and are still largely uncertain of their career plans. We
      believe this proposed course will help students understand aging processes as
      these evolve over time, understand the opportunities that arise from greater life
      expectancy, encourage them to promote their own health, and make a social
      contract to do so for society. 

PMID- 23974511
TI  - Goal-setting in multidisciplinary team care for patients with rheumatoid
      arthritis: an international multi-center evaluation of the contents using the
      International Classification of Functioning, Disability and Health as a
      reference.
AB  - OBJECTIVE: To make a cross-cultural comparison of the contents of rehabilitation
      goals of patients admitted for rehabilitation and to compare the contents with
      the comprehensive International Classification of Functioning, Disability and
      Health (ICF) Core Set for rheumatoid arthritis, by linking their contents to the
      ICF. PATIENTS: A random sample of 80 patients with rheumatoid arthritis was
      retrieved from rehabilitation clinics in 4 countries. METHODS: Rehabilitation
      goals were extracted from the medical records and linked to the ICF using
      standardized linking rules. RESULTS: A total of 495 rehabilitation goals were
      identified and linked to 952 ICF codes, resulting in 151 unique ICF codes. Two
      hundred and seventy-five (29%) of the 952 ICF codes were related to "Body
      Functions" (b-codes), 80 (8%) to "Body Structures" (s-codes), 419 (44%) to
      "Activities and Participation" (d-codes) and 178 (19%) to "Environmental Factors"
      (e-codes). Thirty-five of the 151 unique ICF codes (23%) were not in the
      comprehensive ICF Core Set for RA, whereas 23 of the ICF codes in this Core Set
      (24%) were not in the rehabilitation goals. CONCLUSION: The goals set in a team
      rehabilitation setting for patients with rheumatoid arthritis are related to all
      ICF components, with "Activities and Participation" being the most frequently
      addressed. The contents of the goals are, to a considerable extent, covered by
      the comprehensive ICF Core Set for RA, but additional evaluation is required
      before the ICF Core Set is used as a rehabilitation tool in rheumatoid arthritis.

PMID- 23974512
TI  - The multi-hit hypothesis in basal-like breast cancer.
AB  - It has been known for many years that for a "normal" un-transformed cell to
      become immortal and subsequently tumorigenic requires multiple pro-oncogenic
      changes in the levels of protein expression and function. Genes most commonly
      associated with the process of oncogenesis include: p53 inactivating mutation;
      hDM2 overexpression; p16 reduced expression; K-/H-RAS activating mutation; PTEN
      inactivating mutation/deletion; EGFR activating mutation and overexpression;
      retinoblastoma inactivating mutation and deletion; Cyclin proteins
      overexpression; CD95 reduced expression; protective BCL-2 proteins
      overexpression; to name but just a few of such molecules.(1-5) That the minimally
      required specific proteins for oncogenesis are not known for many specific tumor
      types remains a challenge for the rational design of molecular targeted
      therapies.

PMID- 23974513
TI  - Chemokines and atherosclerosis: focus on the CX3CL1/CX3CR1 pathway.
AB  - Atherosclerosis is currently considered an inflammatory disease. Much attention
      has been focused on the potential role of inflammatory mediators as
      prognostic/diagnostic markers or therapeutic targets of atherosclerotic
      cardiovascular disease. CX3CL1 (or fractalkine) is a structurally and
      functionally unique chemokine with a well documented role in atherosclerosis. In
      its membrane bound form it promotes the firm adhesion of rolling leucocytes onto
      the vessel wall, while in its soluble form it serves as a potent chemoattractant
      for CX3CR1-expressing cells. Additionally, CX3CL1 exerts cytotoxic effects on the
      endothelium as well as anti-apoptotic and proliferative effects on vascular
      cells, affecting the context and stability of the atherosclerotic plaque. Studies
      on animal models have shown that the blockade of the CX3CL1/CX3CR1 pathway
      ameliorates the severity of atherosclerosis, while genetic epidemiology has
      confirmed that a genetically-defined less active CX3CL1/CX3CR1 pathway is
      associated with a reduced risk of atherosclerotic disease in humans. Although
      several studies support an important pathogenic role of CX3CL1/CX3CR1 in
      atherogenesis and plaque destabilization, this does not necessarily suggest that
      this pathway is a suitable therapeutic target or that CX3CL1 can serve as a
      prognostic/diagnostic biomarker. Further studies on the CX3CL1/CX3CR1 chemokine
      pathway are clearly warranted to justify the clinical relevance of its role in
      atherosclerosis.

PMID- 23974514
TI  - Hydrogen sulfide suppresses the expression of MMP-8, MMP-13, and TIMP-1 in left
      ventricles of rats with cardiac volume overload.
AB  - AIM: To study the effects of hydrogen sulfide (H2S) on the left ventricular
      expression of MMP-8, MMP-13, and TIMP-1 in a rat model of congenital heart
      disease. METHODS: Male SD rats underwent abdominal aorta-inferior vena cava shunt
      operation. H2S donor NaHS (56 MUmol.kg(-1).d(-1), ip) was injected from the next
      day for 8 weeks. At 8 weeks, the hemodynamic parameters, including the left
      ventricular systolic pressure (LVSP), the left ventricular peak rate of
      contraction and relaxation (LV +/- dp/dtmax) and the left ventricular end
      diastolic pressure (LVEDP) were measured. The left ventricular tissues were
      dissected out, and hydroxyproline and collagen I contents were detected with
      ELISA. The expression of MMP-8, MMP-13, and a tissue inhibitor of
      metalloproteinase-1 (TIMP-1) in the tissues was measured using real-time PCR,
      Western blotting, and immunohistochemistry, respectively. RESULTS: The shunt
      operation markedly reduced LVSP and LV +/- dp/dtmax, increased LVEDP,
      hydroxyproline and collagen I contents, as well as the mRNA and protein levels of
      MMP-8, MMP-13, and TIMP-1 in the left ventricles. Chronic treatment of the shunt
      operation rats with NaHS effectively prevented the abnormalities in the
      hemodynamic parameters, hydroxyproline and collagen I contents, and the mRNA and
      protein levels of MMP-13 and TIMP-1 in the left ventricles. NaHS also prevented
      the increase of MMP-8 protein expression, but did not affect the increase of mRNA
      level of MMP-8 in the shunt operation rats. CONCLUSION: H2S suppresses protein
      and mRNA expression of MMP-8, MMP-13, and TIMP-1 in rats with cardiac volume
      overload, which may be contributed to the amelioration of ventricular structural
      remodeling and cardiac function.

PMID- 23974515
TI  - Sensitive assay for measurement of volatile borneol, isoborneol, and the
      metabolite camphor in rat pharmacokinetic study of Borneolum (Bingpian) and
      Borneolum syntheticum (synthetic Bingpian).
AB  - AIM: Both Borneolum (Chinese name Bingpian; dextrorotatory borneol) and Borneolum
      syntheticum (synthetic Bingpian; a mixture of optically inactive borneol and
      isoborneol) have been used for medicinal purposes in Chinese traditional
      medicine. The aim of this study was to develop a sensitive assay for measuring
      volatile ingredients borneol, isoborneol, and their metabolite camphor in
      pharmacokinetic study of Bingpian. METHODS: Rat plasma samples were prepared
      using liquid-liquid microextraction: 70 MUL of plasma sample (containing 125
      nmol/L naphthalene as the internal standard) was extracted with 35 MUL of n
      hexane. The resulting n-hexane extract (20 MUL) was introduced into a gas
      chromatography/mass spectrometry system using programmable temperature vaporizing
      based large-volume injection. The assay was validated to demonstrate its
      reliability for the intended use. Using this assay, pharmacokinetic studies of
      Bingpian, synthetic Bingpian, and Fufang-Danshen tablets (containing synthetic
      Bingpian) were conducted in rats. RESULTS: The extraction efficiency for the
      analytes and the internal standard from plasma was almost constant with decrease
      in n-hexane-to-plasma volume ratio, thus enabling a small volume of extracting
      solvent to be used for sample preparation, and enhancing the assay sensitivity.
      The lower quantification limit for measuring borneol, isoborneol, and camphor in
      plasma was 0.98 nmol/L, which was 33-330 times more sensitive than those reported
      earlier for Bingpian and synthetic Bingpian. The applicability of the
      miniaturized liquid-liquid extraction technique could be extended to measure
      other volatile and nonvolatile medicinal compounds in biomatrices, which can be
      predicted according to the analytes' octanol/water distribution coefficient
      (logD) and acid dissociation constant (pKa). CONCLUSION: This assay is sensitive,
      accurate and free of matrix effects, and can be applied to pharmacokinetic
      studies of Bingpian, synthetic Bingpian, and Bingpian-containing herbal products.

PMID- 23974517
TI  - Essential role of autophagy in fucoxanthin-induced cytotoxicity to human
      epithelial cervical cancer HeLa cells.
AB  - AIM: To investigate the effects and the molecular mechanisms of fucoxanthin, a
      major carotenoid found in edible seaweed, on HeLa cells. METHODS: The
      cytotoxicity of fucoxanthin was evaluated using MTT assay. Cell cycle and
      apoptosis were evaluated using flow cytometric analysis. Autophagy was detected
      with acridine orange staining and transient transfection of the GFP-LC3 plasmid
      into the cells. Protein expression was detected with Western blotting. RESULTS:
      Treatment of HeLa cells with fucoxanthin (10-80 MUmol/L) for 48 h caused dose
      dependent cytotoxicity with an IC50 value of 55.1+/-7.6 MUmol/L. Fucoxanthin (10,
      20, and 40 MUmol/L) dose-dependently induced G0/G1 arrest, but did not change the
      apoptosis of HeLa cells. The same concentrations of fucoxanthin dose-dependently
      increased the protein expression of LC3 II (the autophagosome marker) and Beclin
      1 (the initiation factor for autophagosome formation) in HeLa cells. Moreover,
      fucoxanthin dose-dependently decreased the levels of phosphorylated Akt and its
      downstream proteins p53, p70S6K, and mTOR, and increases the expression of PTEN
      in HeLa cells. Pretreatment of HeLa cells with 3-methyladenine (5 mmol/L) blocked
      the cytotoxic effect of fucoxanthin as well as fucoxanthin-induced autophagy.
      CONCLUSION: Fucoxanthin exerts autophagy-dependent cytotoxic effect in HeLa cells
      via inhibition of Akt/mTOR signaling pathway.

PMID- 23974516
TI  - Mast cells and basophils are essential for allergies: mechanisms of allergic
      inflammation and a proposed procedure for diagnosis.
AB  - The current definition of allergy is a group of IgE-mediated diseases. However, a
      large portion of patients with clinical manifestations of allergies do not
      exhibit elevated serum levels of IgE (sIgEs). In this article, three key factors,
      ie soluble allergens, sIgEs and mast cells or basophils, representing the
      causative factors, messengers and primary effector cells in allergic
      inflammation, respectively, were discussed. Based on current knowledge on
      allergic diseases, we propose that allergic diseases are a group of diseases
      mediated through activated mast cells and/or basophils in sensitive individuals,
      and allergic diseases include four subgroups: (1) IgE dependent; (2) other
      immunoglobulin dependent; (3) non-immunoglobulin mediated; (4) mixture of the
      first three subgroups. According to our proposed definition, pseudo-allergic
      reactions, in which mast cell or basophil activation is not mediated via IgE, or
      to a lesser extent via IgG or IgM, should be non-IgE-mediated allergic diseases.
      Specific allergen challenge tests (SACTs) are gold standard tests for diagnosing
      allergies in vivo, but risky. The identification of surface membrane activation
      markers of mast cells and basophils (CD203c, CCR3, CD63, etc) has led to
      development of the basophil activation test (BAT), an in vitro specific allergen
      challenge test (SACT). Based on currently available laboratory allergy tests, we
      here propose a laboratory examination procedure for allergy.

PMID- 23974518
TI  - Rho-kinase inhibitor Y-27632 attenuates pulmonary hypertension in hyperoxia
      exposed newborn rats.
AB  - AIM: To test the hypothesis that neonatal hyperoxia induced pulmonary
      hypertension accompanied by increased Rho-kinase expression in rat lungs and that
      Rho-kinase inhibitor could attenuate right ventricular hypertrophy and pulmonary
      arterial remodeling. METHODS: Newborn rats were exposed to >95% O2 in the first
      week after birth, then to 60% O2 in the following 2 weeks. Control pups were
      exposed to room air over the same periods. The pups were injected with either Rho
      kinase inhibitor Y-27632 (10 mg.kg(-1).d(-1), ip) or vehicle from postnatal d 14
      to 20. Lung and heart tissues were collected on postnatal d 7 and 21. Rho-kinase
      activity in lungs was measured using Western blotting and immunohistochemistry.
      The right ventricular hypertrophy and arterial medial wall thickness (MWT) were
      assessed morphologically. RESULTS: Rho-kinase activity in lungs was comparable
      between the hyperoxic and control pups on postnatal d 7, but it had a more than 2
      fold increase in the hyperoxic pups on postnatal d 21. Moreover, the hyperoxic
      exposure induced structural features of pulmonary hypertension, as shown by the
      right ventricular hypertrophy and significantly increased arterial MWT.
      Administration with Y-27632 effectively blocked the hyperoxia-induced increase of
      Rho-kinase activity in lungs, and attenuated the right ventricular hypertrophy.
      CONCLUSION: Rho-kinase inhibitor may be a novel therapy for attenuating the
      hyperoxia-induced structural changes in pulmonary hypertension.

PMID- 23974519
TI  - Adaptive long-range migration promotes cooperation under tempting conditions.
AB  - Migration is a fundamental trait in humans and animals. Recent studies
      investigated the effect of migration on the evolution of cooperation, showing
      that contingent migration favors cooperation in spatial structures. In those
      studies, only local migration to immediate neighbors was considered, while long
      range migration has not been considered yet, partly because the long-range
      migration has been generally regarded as harmful for cooperation as it would
      bring the population to a well-mixed state that favors defection. Here, we
      studied the effects of adaptive long-range migration on the evolution of
      cooperation through agent-based simulations of a spatial Prisoner's Dilemma game
      where individuals can jump to a farther site if they are surrounded by more
      defectors. Our results show that adaptive long-range migration strongly promotes
      cooperation, especially under conditions where the temptation to defect is
      considerably high. These findings demonstrate the significance of adaptive long
      range migration for the evolution of cooperation. 

PMID- 23974520
TI  - Single-mode tunable laser emission in the single-exciton regime from colloidal
      nanocrystals.
AB  - Whispering-gallery-mode resonators have been extensively used in conjunction with
      different materials for the development of a variety of photonic devices. Among
      the latter, hybrid structures, consisting of dielectric microspheres and
      colloidal core/shell semiconductor nanocrystals as gain media, have attracted
      interest for the development of microlasers and studies of cavity quantum
      electrodynamic effects. Here we demonstrate single-exciton, single-mode,
      spectrally tuned lasing from ensembles of optical antenna-designed, colloidal
      core/shell CdSe/CdS quantum rods deposited on silica microspheres. We obtain
      single-exciton emission by capitalizing on the band structure of the specific
      core/shell architecture that strongly localizes holes in the core, and the two
      dimensional quantum confinement of electrons across the elongated shell. This
      creates a type-II conduction band alignment driven by coulombic repulsion that
      eliminates non-radiative multi-exciton Auger recombination processes, thereby
      inducing a large exciton-bi-exciton energy shift. Their ultra-low thresholds and
      single-mode, single-exciton emission make these hybrid lasers appealing for
      various applications, including quantum information processing. 

PMID- 23974521
TI  - Bioluminescence tomography by an iterative reweighted (l)2 norm optimization.
AB  - Bioluminescence tomography is a promising tool in preclinical research, enabling
      noninvasive real-time in vivo imaging as well as quantitative analysis in small
      animal studies. Due to the difficulty of reconstruction, continuous efforts are
      still made to find more practical and efficient approaches. In this paper, we
      present an iterative reweighted l2-norm optimization incorporating anatomical
      structures in order to enhance the performance of bioluminescence tomography. The
      structure priors have been utilized to generate a heterogeneous mouse model by
      extracting the internal organs and tissues, which can assist in establishing a
      more precise photon diffusion model, as well as reflecting a more specific
      position of the reconstruction results inside the mouse. To evaluate the
      performance of the iterative reweighted approach, several numerical simulation
      studies including comparative analyses and multisource cases have been conducted
      to reconstruct the same datasets. The results suggest that the proposed method is
      able to ensure the accuracy, robustness, and efficiency of bioluminescence
      tomography. Finally, an in vivo experiment was performed to further validate its
      feasibility in a practical application. 

PMID- 23974522
TI  - Multimodal medical volumetric data fusion using 3-D discrete shearlet transform
      and global-to-local rule.
AB  - Traditional two-dimensional (2-D) fusion framework usually suffers from the loss
      of the between-slice information of the third dimension. For example, the fusion
      of three-dimensional (3-D) MRI slices must account for the information not only
      within the given slice but also the adjacent slices. In this paper, a fusion
      method is developed in 3-D shearlet space to overcome the drawback. On the other
      hand, the popularly used average-maximum fusion rule can capture only the local
      information but not any of the global information for it is implemented in a
      local window region. Thus, a global-to-local fusion rule is proposed. We firstly
      show the 3-D shearlet coefficients of the high-pass subbands are highly non
      Gaussian. Then, we show this heavy-tailed phenomenon can be modeled by the
      generalized Gaussian density (GGD) and the global information between two
      subbands can be described by the Kullback-Leibler distance (KLD) of two GGDs. The
      finally fused global information can be selected according to the asymmetry of
      the KLD. Experiments on synthetic data and real data demonstrate that better
      fusion results can be obtained by the proposed method. 

PMID- 23974523
TI  - Wireless tissue palpation for intraoperative detection of lumps in the soft
      tissue.
AB  - In an open surgery, identification of precise margins for curative tissue
      resection is performed by manual palpation. This is not the case for minimally
      invasive and robotic procedures, where tactile feedback is either distorted or
      not available. In this paper, we introduce the concept of intraoperative wireless
      tissue palpation. The wireless palpation probe (WPP) is a cylindrical device (15
      mm in diameter, 60 mm in length) that can be deployed through a trocar incision
      and directly controlled by the surgeon to create a volumetric stiffness
      distribution map of the region of interest. This map can then be used to guide
      the tissue resection to minimize healthy tissue loss. The wireless operation
      prevents the need for a dedicated port and reduces the chance of instrument
      clashing in the operating field. The WPP is able to measure in real time the
      indentation pressure with a sensitivity of 34 Pa, the indentation depth with an
      accuracy of 0.68 mm, and the probe position with a maximum error of 11.3 mm in a
      tridimensional workspace. The WPP was assessed on the benchtop in detecting the
      local stiffness of two different silicone tissue simulators (elastic modulus
      ranging from 45 to 220 kPa), showing a maximum relative error below 5%. Then, in
      vivo trials were aimed to identify an agar-gel lump injected into a porcine liver
      and to assess the device usability within the frame of a laparoscopic procedure.
      The stiffness map created intraoperatively by the WPP was compared with a map
      generated ex vivo by a standard uniaxial material tester, showing less than 8%
      local stiffness error at the site of the lump.

PMID- 23974524
TI  - Determination of the learning curve for ultrasound-guided jugular central venous
      catheter placement.
AB  - PURPOSE: Use of ultrasound (US) when introducing central venous catheters (CVC)
      may improve success rates, reduce the number of needle punctures, and decrease
      complication rates, but has been hampered by supposed difficulty in learning how
      to perform the technique. This study describes the learning curve for US-guided
      jugular CVC placement after a training program. METHODS: After an initial slide
      presentation and a video, intensivists who had not previously used US for CVC
      placement were evaluated qualitatively for US set up (score S1) and technical
      skills (score S2). Quantitative measures included durations of different
      components of the procedure (T1, time from entry of the US into the patient's
      room to sterile dressing of the intensivist; T2, time needed for sterile drapes,
      venous line preparation, and sterile sheath placement; T3, time from skin
      puncture to venous flashback; T4, time from guide insertion to dressing; T(tot),
      total duration of the procedure); number of skin punctures; and a difficulty
      score allocated by the intensivist. RESULTS: We performed 150 evaluations of 30
      intensivists: 50% had no prior experience of CVC placement and 50% no prior US
      experience. Maximal S1 and S2 scores were obtained with the fourth and eighth
      placement procedures, respectively. T1 and T2 did not change with ongoing
      training (5 and 8 min, respectively), but T3 and T4 decreased, from 5 min (first
      procedure) to less than 1 min (seventh procedure), and from 10 min (first
      procedure) to 7 min (sixth procedure), respectively. T(tot) decreased from 34 to
      21 min at the eighth procedure. The number of skin punctures and the difficulty
      score decreased rapidly with the number of evaluations. CONCLUSIONS: Our study
      demonstrates that skills in US-guided CVC placement can easily be acquired with
      training.

PMID- 23974525
TI  - Advantages of using development models of the carrion beetles Thanatophilus
      micans (Fabricius) and T. mutilatus (Castelneau) (Coleoptera: Silphidae) for
      estimating minimum post mortem intervals, verified with case data.
AB  - Some beetles are as useful as blow flies for estimating the minimum post mortem
      interval (PMImin) or time since death. Examples include Thanatophilus micans
      (Fabricius) and Thanatophilus mutilatus (Castelneau), two geographically and
      ecologically overlapping African beetles. Molecular means of identifying these
      species, descriptions of their natural history, thermal summation models for the
      development of each species, and a case in which T. micans was recovered are
      presented. These beetles colonise bodies soon after death, their development
      spans more time than that of flies, and they may be little affected by maggot
      generated heat. From an experimental perspective, they can be reared
      individually, which allows the identification of sick individuals and has
      analytical advantages relative to fly larvae that must be reared in groups.
      Estimating minimum post mortem intervals for both species using the case data
      strongly suggests that developmental models parameterised for one species should
      not be used to make forensic estimates for closely related species for which no
      specific model is available and emphasises the need for correct identifications. 

PMID- 23974526
TI  - Synergids and filiform apparatus in the sexual and apomictic dandelions from
      section Palustria (Taraxacum, Asteraceae).
AB  - An evolutionary trend to reduce "unnecessary costs" associated with the sexual
      reproduction of their amphimictic ancestors, which may result in greater
      reproductive success, has been observed among the obligatory apomicts. However,
      in the case of the female gametophyte, knowledge about this trend in apomicts is
      not sufficient because most of the ultrastructural studies of the female
      gametophyte have dealt with amphimictic angiosperms. In this paper, we tested the
      hypothesis that, in contrast to amphimictic plants, synergids in apomictic embryo
      sacs do not form a filiform apparatus. We compared the synergid structure in two
      dandelions from sect. Palustria: the amphimictic diploid Taraxacum tenuifolium
      and the apomictic tetraploid, male-sterile Taraxacum brandenburgicum. Synergids
      in both species possessed a filiform apparatus. In T. brandenburgicum, both
      synergids persisted for a long time without any degeneration, in spite of the
      presence of an embryo and endosperm. We propose that the persistent synergids in
      apomicts may play a role in the transport of nutrients to the embryo.

PMID- 23974528
TI  - Role of dyslipidemia in impairment of energy metabolism, oxidative stress,
      inflammation and cardiovascular disease in chronic kidney disease.
AB  - Advanced chronic kidney disease (CKD) results in a constellation of dysregulation
      of lipid metabolism, oxidative stress, and inflammation which are causally
      interconnected and participate in a vicious cycle. The CKD-associated lipid
      disorders are marked by impaired clearance of very low density lipoprotein and
      chylomicrons, hypertriglyceridemia, formation of small dense low-density
      lipoprotein (LDL), oxidative modification of LDL, intermediate density
      lipoprotein and chylomicron remnants, and high-density lipoprotein deficiency and
      dysfunction. This review provides a brief overview of the role of CKD-induced
      lipid disorders in the pathogenesis of oxidative stress, inflammation,
      cardiovascular disease, impaired exercise capacity, cachexia and wasting
      syndrome. 

PMID- 23974530
TI  - An integrated anaerobic digestion and UV photocatalytic treatment of distillery
      wastewater.
AB  - Anaerobic up-flow fixed bed reactor and annular photocatalytic reactor were used
      to study the efficiency of integrated anaerobic digestion (AD) and ultraviolet
      (UV) photodegradation of real distillery effluent and raw molasses wastewater
      (MWW). It was found that UV photodegradation as a stand-alone technique achieved
      colour removal of 54% and 69% for the distillery and MWW, respectively, with a
      COD reduction of <20% and a negligible BOD reduction. On the other hand, AD as a
      single treatment technique was found to be effective in COD and BOD reduction
      with efficiencies of above 75% and 85%, respectively, for both wastewater
      samples. However, the AD achieved low colour removal efficiency, with an increase
      in colour intensity of 13% recorded when treating MWW while a colour removal of
      51% was achieved for the distillery effluent. The application of UV
      photodegradation as a pre-treatment method to the AD process reduced the COD
      removal and biogas production efficiency. However, an integration in which UV
      photodegradation was employed as a post-treatment to the AD process achieved high
      COD removal of above 85% for both wastewater samples, and colour removal of 88%
      for the distillery effluent. Thus, photodegradation can be employed as a post
      treatment technique to an AD system treating distillery effluent for complete
      removal of the biorecalcitrant and colour imparting compounds.

PMID- 23974529
TI  - All-carbon-nanotube flexible multi-electrode array for neuronal recording and
      stimulation.
AB  - Neuro-prosthetic devices aim to restore impaired function through artificial
      stimulation of the nervous system. A lingering technological bottleneck in this
      field is the realization of soft, micron sized electrodes capable of injecting
      enough charge to evoke localized neuronal activity without causing neither
      electrode nor tissue damage. Direct stimulation with micro electrodes will offer
      the high efficacy needed in applications such as cochlear and retinal implants.
      Here we present a new flexible neuronal micro electrode device, based entirely on
      carbon nanotube technology, where both the conducting traces and the stimulating
      electrodes consist of conducting carbon nanotube films embedded in a polymeric
      support. The use of carbon nanotubes bestows the electrodes flexibility and
      excellent electrochemical properties. As opposed to contemporary flexible
      neuronal electrodes, the technology presented here is both robust and the
      resulting stimulating electrodes are nearly purely capacitive. Recording and
      stimulation tests with chick retinas were used to validate the advantageous
      properties of the electrodes and demonstrate their suitability for high-efficacy
      neuronal stimulation applications. 

PMID- 23974531
TI  - Alachlor oxidation by the filamentous fungus Paecilomyces marquandii.
AB  - Alachlor, a popular chloroacetanilide herbicide, can be a potential health risk
      factor. Soil microorganisms are primarily responsible for conversion and
      migration of alachlor in natural environment, but knowledge concerning alachlor
      biodegradation is not complete. Therefore, we studied the ability of Paecilomyces
      marquandii, soil fungus tolerant to heavy metals, to eliminate alachlor and
      proposed a new pathway of its transformation. After 7 days of incubation only
      3.3% of alachlor was detected from an initial concentration 50 mg L(-1) and 20.1%
      from a concentration 100 mg L(-1). The qualitative IDA LC-MS analysis showed the
      presence of ten metabolites. All of them were dechlorinated mainly through
      oxidation, but also reductive dechlorination was observed. The main route of
      alachlor conversion progressed via N-acetyl oxidation resulting in the formation
      of mono-, di- and trihydroxylated byproducts. N-acetyl oxidation as a dominant
      route of alachlor metabolism by fungi has not been described so far. The toxicity
      of alachlor tested with Artemia franciscana did not increase after treatment with
      P. marquandii cultures. Paecilomyces marquandii strain seems to be an interesting
      model for the research on alachlor conversion by soil microscopic fungi, due to
      its dechlorination and hydroxylation ability as well as high tolerance to heavy
      metals.

PMID- 23974532
TI  - Degradation of polychlorinated biphenyls using mesoporous iron-based spinels.
AB  - A series of mesoporous iron-based spinel materials were synthesized to degrade
      polychlorinated biphenyls (PCBs), with CB-209 being used as a model compound. The
      materials were characterized by X-ray powder diffraction (XRD), pore structure
      analysis, and X-ray photoelectron spectroscopy (XPS). A comparison of the
      dechlorination efficiencies (DEs) of the materials revealed that NiFe2O4 had the
      highest DE, followed by Fe3O4. Newly produced polychlorinated biphenyls,
      chlorinated benzenes, hydroxyl species and organic acids were detected by gas
      chromatography-mass spectrometry, high performance liquid chromatography-mass
      spectrometry and ion chromatograph. Identification of the intermediate products
      indicates that three degradation pathways, hydrodechlorination, the breakage of
      CC bridge bond and oxidative reaction, accompanied by one combination reaction,
      are competitively occurring over the iron-based spinels. The relative amounts of
      produced three NoCB isomers were illustrated by the CCl BDEs of CB-209 at meta-,
      para- and ortho-positions, and their energy gap between HOMO and LUMO. The
      consumption of the reactive oxygen species caused by the transformation of Fe3O4
      into Fe2O3 in the Fe3O4 reaction system, and the existence of the highly reactive
      O2(-) species in the NiFe2O4 reaction system, could provide a reason why the
      oxidation reaction was more favored over NiFe2O4 than Fe3O4.

PMID- 23974533
TI  - Modeling of nitrate concentration in groundwater using artificial intelligence
      approach--a case study of Gaza coastal aquifer.
AB  - Nitrate concentration in groundwater is influenced by complex and interrelated
      variables, leading to great difficulty during the modeling process. The
      objectives of this study are (1) to evaluate the performance of two artificial
      intelligence (AI) techniques, namely artificial neural networks and support
      vector machine, in modeling groundwater nitrate concentration using scant input
      data, as well as (2) to assess the effect of data clustering as a pre-modeling
      technique on the developed models' performance. The AI models were developed
      using data from 22 municipal wells of the Gaza coastal aquifer in Palestine from
      2000 to 2010. Results indicated high simulation performance, with the correlation
      coefficient and the mean average percentage error of the best model reaching
      0.996 and 7 %, respectively. The variables that strongly influenced groundwater
      nitrate concentration were previous nitrate concentration, groundwater recharge,
      and on-ground nitrogen load of each land use land cover category in the well's
      vicinity. The results also demonstrated the merit of performing clustering of
      input data prior to the application of AI models. With their high performance and
      simplicity, the developed AI models can be effectively utilized to assess the
      effects of future management scenarios on groundwater nitrate concentration,
      leading to more reasonable groundwater resources management and decision-making. 

PMID- 23974534
TI  - Application of the positive matrix factorization approach to identify heavy metal
      sources in sediments. A case study on the Mexican Pacific Coast.
AB  - During the last two decades, sediments collected in different sources of water
      bodies of the Tehuantepec Basin, located in the southeast of the Mexican Pacific
      Coast, showed that concentrations of heavy metals may pose a risk to the
      environment and human health. The extractable organic matter, geoaccumulation
      index, and enrichment factors were quantified for arsenic, cadmium, copper,
      chromium, nickel, lead, vanadium, zinc, and the fine-grained sediment fraction.
      The non-parametric SiZer method was applied to assess the statistical
      significance of the reconstructed metal variation along time. This inference
      method appears to be particularly natural and well suited to temperature and
      other environmental reconstructions. In this approach, a collection of smooth of
      the reconstructed metal concentrations is considered simultaneously, and
      inferences about the significance of the metal trends can be made with respect to
      time. Hence, the database represents a consolidated set of available and
      validated water and sediment data of an urban industrialized area, which is very
      useful as case study site. The positive matrix factorization approach was used in
      identification and source apportionment of the anthropogenic heavy metals in the
      sediments. Regionally, metals and organic matter are depleted relative to crustal
      abundance in a range of 45-55 %, while there is an inorganic enrichment from
      lithogenous/anthropogenic sources of around 40 %. Only extractable organic
      matter, Pb, As, and Cd can be related with non-crustal sources, suggesting that
      additional input cannot be explained by local runoff or erosion processes. 

PMID- 23974535
TI  - Mercury in various tissues of three mustelid species and other trace metals in
      liver of European otter from Eastern Finland.
AB  - Mercury concentrations were monitored in European otter (Lutra lutra), European
      polecat (Mustela putorius) and European pine marten (Martes martes) collected in
      Eastern Finland during the period 1972-2008. Otters mainly eat fish, which is an
      important reason to monitor the bioaccumulation of mercury in this predator. In
      this species, the highest concentrations were found in fur followed by liver and
      kidney, and the mercury concentrations increased with increasing age and body
      weight. Males showed in general higher concentrations than females of otters. The
      food of European polecat consists of small mammals, frogs, birds and insects from
      both aquatic and terrestrial food chains. The mercury concentrations were lower
      than in otters without significant differences related to body weight or sex. In
      European pine martens, the concentrations were rather evenly distributed except
      for two specimens with high concentrations. Also, concentrations of some other
      metals (Al, Cd, Cu, Fe, Mn, Ni, Pb and Zn) were analysed from liver samples of
      otter. Possible adverse effects of mercury on the Finnish populations of these
      mustelids are discussed. 

PMID- 23974536
TI  - Evaluating the effect of rainfall variability on vegetation establishment in a
      semidesert grassland.
AB  - Of the operations required for reclamation in arid and semi-arid regions,
      establishing vegetation entails the most uncertainty due to reliance on
      unpredictable rainfall for seed germination and seedling establishment. The
      frequency of successful vegetation establishment was estimated based on a land
      surface model driven by hourly atmospheric forcing data, 7 years of eddy-flux
      data, and 31 years of rainfall data at two adjacent sites in southern Arizona,
      USA. Two scenarios differing in the required imbibition time for successful
      germination were evaluated-2 or 3 days availability of sufficient surface
      moisture. Establishment success was assumed to occur if plants could germinate
      and if the drying front in the soil did not overtake the growth of seminal roots.
      Based on our results, vegetation establishment could be expected to fail in 32 %
      of years. In the worst 10-year span, six of ten plantings would have failed. In
      the best 10-year span, only one of ten was projected to fail. Across all
      assessments, at most 3 years in a row failed and 6 years in a row were
      successful. Funding for reclamation seeding must be available to allow reseeding
      the following year if sufficient amount and timing of rainfall does not occur. 

PMID- 23974537
TI  - Effects of northeast monsoon on trace metal distribution in the South China Sea
      off Peninsular Malaysia.
AB  - Concentrations of trace metals in the South China Sea (SCS) were determined off
      the coast of Terengganu during the months of May and November 2007. The
      concentrations of dissolved and particulate metals were in the range of 0.019
      0.194 MUg/L and 50-365 MUg/g, respectively, for cadmium (Cd), 0.05-0.45 MUg/L and
      38-3,570 MUg/g for chromium (Cr), 0.05-3.54 MUg/L and 21-1,947 MUg/g for
      manganese (Mn), and 0.03-0.49 MUg/L and 2-56,982 MUg/g for lead (Pb). The order
      of mean log K D found was Cd > Cr > Pb > Mn. The study suggests that the primary
      sources of these metals are discharges from the rivers which drain into the SCS,
      in particular the Dungun River, which flows in close proximity to agricultural
      areas and petrochemical industries. During the northeast monsoon, levels of
      particulate metals in the bottom water samples near the shore were found to be
      much higher than during the dry season, the probable result of re-suspension of
      the metals from the bottom sediments. 

PMID- 23974539
TI  - Professor john bryden.

PMID- 23974538
TI  - Scaling up Health Informatics.

PMID- 23974540
TI  - Sedick isaacs.

PMID- 23974541
TI  - Looking for the evidence: value of health informatics. Editorial.
AB  - OBJECTIVES: To provide an editorial introduction to the 2013 IMIA Yearbook of
      Medical Informatics with an overview of its contents and contributors. METHODS: A
      brief overview of the main theme, and an outline of the purposes, contents,
      format, and acknowledgment of contributions. RESULTS: Health information
      technology (HIT) is currently widely implemented to improve healthcare quality
      and patient safety while reducing costs. Although these benefits are expected and
      largely advertised, the evidence for these benefits is still missing. Unintended
      consequences are often reported and some applications have been shown to be
      wasteful, harmful, and even fatal. Evidence-based health informatics has been
      defined as "the conscientious, explicit and judicious use of current best
      evidence when making decisions about the introduction and operation of
      information technology in a given health care setting". The 2013 issue of the
      IMIA Yearbook highlights important contributions about the significant challenges
      that arise from the assessment of HIT solutions. Progress towards evidence-based
      health informatics is identified to elicit what works, what doesn't work, and
      why. In an environment where resources are limited, budgets lower than in past
      years, and the need to improve care is becoming ever more pressing, focusing on
      this topic should guide institutions and providers in the implementation of the
      best health information technology. CONCLUSION: This overview of progress and
      current challenges across the spectrum of the discipline shows many great
      examples of evidence that have been gathered on the effectiveness of HIT.
      However, evidence remains limited and a significant work should be conducted to
      improve the development, testing, and implementation of HIT applications.

PMID- 23974542
TI  - Is healthcare information technology based on evidence?
AB  - Is healthcare information technology (HIT) based on evidence of efficacy? Are the
      trillions of dollars already devoted and in the pipeline for HIT implementations
      based on systematic evaluations? If evaluated, would those evaluations focus on
      patient safety, return on investment, clinical efficiency, improved clinician
      satisfaction, and/or workflow integration? Do we have reliable evidence of usable
      interfaces, of successful implementations, of data standards allowing
      interoperability, of continuous improvement, of responsiveness to clinician
      feedback? While measurement of HIT's efficacy is extraordinarily difficult
      complicated by a myriad of other factors involved in providing healthcare and in
      organizational dynamics-it is not impossible. But is such evidence required
      before most implementations? Any implementation? Or are the goals of patient
      safety and efficiency so self-evident, profoundly desired, and laudable that
      HIT's beneficence is accepted without rigorous data? Note that lack of systematic
      evidence does not mean HIT is ineffective. HIT may provide untold benefits even
      if there is no hard proof of those benefits. We find that HIT is seldom
      objectively measured, and that evidence of its efficacy is at best spotty, and
      often influenced by self-promotion. Most measures, especially those associated
      with cost-benefit analyses, are aspirational or hubris transubstantiated into
      numbers. 

PMID- 23974543
TI  - State of the art in clinical informatics: evidence and examples.
AB  - OBJECTIVE: The field of clinical informatics has expanded substantially in the
      six decades since its inception. Early research focused on simple demonstrations
      that health information technology (HIT) such as electronic health records
      (EHRs), computerized provider order entry (CPOE), and clinical decision support
      (CDS) systems were feasible and potentially beneficial in clinical practice.
      METHODS: In this review, we present recent evidence on clinical informatics in
      the United States covering three themes: 1) clinical informatics systems and
      interventions for providers, including EHRs, CPOE, CDS, and health information
      exchange; 2) consumer health informatics systems, including personal health
      records and web-based and mobile HIT; and 3) methods and governance for clinical
      informatics, including EHR usability; data mining, text mining, natural language
      processing, privacy, and security. RESULTS: Substantial progress has been made in
      demonstrating that various clinical informatics methodologies and applications
      improve the structure, process, and outcomes of various facets of the healthcare
      system. CONCLUSION: Over the coming years, much more will be expected from the
      field. As we move past the "early adopters" in Rogers' diffusion of innovations'
      curve through the "early majority" and into the "late majority," there will be a
      crucial need for new research methodologies and clinical applications that have
      been rigorously demonstrated to work (i.e., to improve health outcomes) in
      multiple settings with different types of patients and clinicians.

PMID- 23974544
TI  - Usability Methods for Ensuring Health Information Technology Safety: Evidence
      Based Approaches. Contribution of the IMIA Working Group Health Informatics for
      Patient Safety.
AB  - OBJECTIVES: Issues related to lack of system usability and potential safety
      hazards continue to be reported in the health information technology (HIT)
      literature. Usability engineering methods are increasingly used to ensure
      improved system usability and they are also beginning to be applied more widely
      for ensuring the safety of HIT applications. These methods are being used in the
      design and implementation of many HIT systems. In this paper we describe evidence
      based approaches to applying usability engineering methods. METHODS: A multi
      phased approach to ensuring system usability and safety in healthcare is
      described. Usability inspection methods are first described including the
      development of evidence-based safety heuristics for HIT. Laboratory-based
      usability testing is then conducted under artificial conditions to test if a
      system has any base level usability problems that need to be corrected. Usability
      problems that are detected are corrected and then a new phase is initiated where
      the system is tested under more realistic conditions using clinical simulations.
      This phase may involve testing the system with simulated patients. Finally, an
      additional phase may be conducted, involving a naturalistic study of system use
      under real-world clinical conditions. RESULTS: The methods described have been
      employed in the analysis of the usability and safety of a wide range of HIT
      applications, including electronic health record systems, decision support
      systems and consumer health applications. It has been found that at least
      usability inspection and usability testing should be applied prior to the
      widespread release of HIT. However, wherever possible, additional layers of
      testing involving clinical simulations and a naturalistic evaluation will likely
      detect usability and safety issues that may not otherwise be detected prior to
      widespread system release. CONCLUSION: The framework presented in the paper can
      be applied in order to develop more usable and safer HIT, based on multiple
      layers of evidence.

PMID- 23974545
TI  - Health Informatics in Developing Countries: Systematic Review of Reviews.
      Contribution of the IMIA Working Group Health Informatics for Development.
AB  - OBJECTIVES: An evidence-base is important for medicine and health informatics.
      Despite numerous publications showing the benefits of health informatics, the
      emergence of health information systems in developing countries has been slower
      than expected. The aim of this paper is to identify systematic reviews on the
      domain of health informatics in developing countries, and classify the different
      types of applications covered. METHODS: A systematic review of reviews was
      conducted. The literature search spanned the time period between 2000 and 2012
      and included PubMed, EMBASE, CINAHL, Scopus, Cochrane Systematic Reviews, LILACS,
      and Google Scholar. The search term was 'systematic reviews of health informatics
      in developing countries', and transparent and systematic procedures were applied
      to limit bias at all stages. RESULTS: Of the 982 identified articles, only 10 met
      the inclusion criteria and one more article was added in a second manual search,
      resulting in a total of 11 systematic reviews for the analysis. CONCLUSIONS:
      Although it was difficult to find high quality resources on the selected domain,
      the best evidence available allowed us to generate this report and create an
      incipient review of the state of the art in health informatics in the developing
      countries. More studies will be needed to optimize the results.

PMID- 23974546
TI  - Evidence Based Health Informatics: 10 Years of Efforts to Promote the Principle.
      Joint Contribution of IMIA WG EVAL and EFMI WG EVAL.
AB  - OBJECTIVES: To present the importance of Evidence-based Health Informatics (EBHI)
      and the ethical imperative of this approach; to highlight the work of the IMIA
      Working Group on Technology Assessment and Quality Improvement and the EFMI
      Working Group on Assessment of Health Information Systems; and to introduce the
      further important evaluation and evidence aspects being addressed. METHODS:
      Reviews of IMIA, EFMA and other initiatives, together with literature reviews on
      evaluation methods and on published systematic reviews. RESULTS: Presentation of
      the rationale for the health informatics domain to adopt a scientific approach by
      assessing impact, avoiding harm, and empirically demonstrating benefit and best
      use; reporting of the origins and rationale of the IMIA- and EQUATOR-endorsed
      Statement on Reporting of Evaluation Studies in Health Informatics (STARE-HI) and
      of the IMIA WG's Guideline for Good Evaluation Practice in Health Informatics
      (GEP-HI); presentation of other initiatives for objective evaluation; and
      outlining of further work in hand on usability and indicators; together with the
      case for development of relevant evaluation methods in newer applications such as
      telemedicine. The focus is on scientific evaluation as a reliable source of
      evidence, and on structured presentation of results to enable easy retrieval of
      evidence. CONCLUSIONS: EBHI is feasible, necessary for efficiency and safety, and
      ethically essential. Given the significant impact of health informatics on health
      systems, care delivery and personal health, it is vital that cultures change to
      insist on evidence-based policies and investment, and that emergent global moves
      for this are supported.

PMID- 23974547
TI  - Evidence-based Biomedical Informatics. The Long Way from Pioneer to Science.
AB  - OBJECTIVES: An overview of current trends and achievements in building more
      evidence of using information sciences technologies in biomedical informatics.
      METHODS: Extensive search using PubMed for published papers in this field in
      2012. A selection process organized in three steps: a) identification and first
      selection of papers; b) international peer-review by at least 4 reviewers for
      each paper; c) final selection of five papers by the editorial board of the
      Yearbook based on the international reviewing results and a balanced coverage of
      the topics. RESULTS: Synopsis of the articles selected for the IMIA Yearbook 2012
      and an invited opinion paper written by leading scientists in this field.
      CONCLUSION: Evidence based health informatics is an important and ubiquitous
      trend in biomedical informatics. However, this research field has to be enhanced
      even further and, more importantly, achievements have to be put in practice.

PMID- 23974548
TI  - A scoping review of telehealth.
AB  - OBJECTIVES: This scoping review of the telehealth literature over the past year
      was conducted to provide a snapshot of some of the current developments in the
      field. As with any scoping review, only a subset of papers was examined, and the
      rigorous methods of a systematic review are not applied. METHODS: We surveyed
      selected dimensions of the current literature, specifically targeting telehealth
      or eHealth interventions at the patient (or micro) level in this scoping review.
      Considering the lack of clarity around the terms like mHealth, eHealth,
      telehealth, and telemedicine, efforts were made understand and harmonize the
      terminology as part of the review process. RESULTS: A total of 171 papers that
      matched the search criteria were culled from the literature. After discussion and
      debate, a total of 26 papers were retained and classified into at least one of 5
      conceptual categories that were derived form a concept analysis. The five
      categories are Preventive and Therapeutic Effects; Health Service Utilization;
      Challenges & Opportunities for Enhanced User Centered Design; Low-powered
      studies/inconclusive evidence; and Future trends in telehealth. Each of these 5
      concept categories are discussed to provide a better understanding of present
      opportunities, challenges, and the overall prospects for telehealth advancement.
      CONCLUSIONS: The field is expanding and maturing rapidly. There is a need for
      larger scale studies that balance rigor while reducing translational latency.
      Additional attention to implementation science methods is recommended as global
      telehealth projects accelerate.

PMID- 23974549
TI  - eHealth in Europe - Status and Challenges.
AB  - OBJECTIVES: To present European reflections on the concept of eHealth and
      emerging challenges related to further development of eHealth in Europe. METHODS:
      A survey with 10 questions was distributed to representatives of the national
      member associations of the European Federation of Medical Informatics (EFMI).
      RESULTS: The results document a shift from a constricting ICT-orientation to
      development of the entire health system where eHealth strategies, organizational
      change, and appropriate technological infrastructure are singled out as important
      aspects. CONCLUSION: There are urgent needs to ensure that eHealth strategies and
      policies for further design and deployment of eHealth applications support
      sociable services and innovations in health care.

PMID- 23974550
TI  - Trends on integrating technologies for mobile and personalized care. Findings
      from the section on health and clinical management.
AB  - OBJECTIVES: Summarize current excellent research and trends in the field of
      Health and Clinical Management. METHOD: Synopsis of the articles selected for the
      IMIA Yearbook 2013. RESULTS: Five papers from international peer-reviewed
      journals have been selected for the section of Health and Clinical Management.
      CONCLUSIONS: The selected articles illustrate current research regarding the
      Health and Clinical Management and showed that it is impacted by the importance
      of personalizing the care and integrating the use of mobile and connected
      technologies.

PMID- 23974551
TI  - Evolution of human factors research and studies of health information
      technologies: the role of patient safety.
AB  - OBJECTIVES: The objective of this survey paper is to present and explain the
      impact of recent regulations and patient safety initiatives (EU, US and Canada)
      on Human Factors (HF)/Usability studies and research focusing on Health
      Information Technology (HIT). METHODS: The authors have selected the most
      prominent of these recent regulations and initiatives, which rely on validated HF
      and usability methods and concepts and aim at enhancing the specific process of
      identification and prevention of technology-induced errors throughout the
      lifecycle of HIT. RESULTS: The analysis highlights several points of consensus:
      1) safety initiatives or regulations applicable to Medical Devices (MD) tend to
      extend to HIT, 2) Usability is considered a fundamental dimension of HIT safety,
      3) HF/Usability methods and the overall Human Centred Design (HCD) approach are
      considered efficient solutions to ensure the design of safe and usable HIT.
      However, it appears that MD manufacturers, and a fortiori HIT designers and
      developers are still far from being able to routinely apply HCD to their
      products. DISCUSSION AND CONCLUSION: On the research side, we need to analyze
      manufacturers' difficulties with the application of the HCD process and imposed
      standards. For each given category of HIT, we need to identify the fundamental
      usability dimensions and design principles likely to impact patient safety
      independently of workplace settings or organizations. These should be described
      in terms of usability flaws, corresponding usage problems experienced by users
      and related outcomes. This approach requires good quality and well structured
      reporting of Human Factors / Usability research studies on HIT.

PMID- 23974552
TI  - From Usability Testing to Clinical Simulations: Bringing Context into the Design
      and Evaluation of Usable and Safe Health Information Technologies. Contribution
      of the IMIA Human Factors Engineering for Healthcare Informatics Working Group.
AB  - OBJECTIVES: The objective of this paper is to explore human factors approaches to
      understanding the use of health information technology (HIT) by extending
      usability engineering approaches to include analysis of the impact of clinical
      context through use of clinical simulations. METHODS: Methods discussed are
      considered on a continuum from traditional laboratory-based usability testing to
      clinical simulations. Clinical simulations can be conducted in a simulation
      laboratory and they can also be conducted in real-world settings. The clinical
      simulation approach attempts to bring the dimension of clinical context into
      stronger focus. This involves testing of systems with representative users doing
      representative tasks, in representative settings/environments. RESULTS:
      Application of methods where realistic clinical scenarios are used to drive the
      study of users interacting with systems under realistic conditions and settings
      can lead to identification of problems and issues with systems that may not be
      detected using traditional usability engineering methods. In conducting such
      studies, careful consideration is needed in creating ecologically valid test
      scenarios. The evidence obtained from such evaluation can be used to improve both
      the usability and safety of HIT. In addition, recent work has shown that clinical
      simulations, in particular those conducted in-situ, can lead to considerable
      benefits when compared to the costs of running such studies. CONCLUSION: In order
      to bring context of use into the testing of HIT, clinical simulation, involving
      observing representative users carrying out tasks in representative settings,
      holds considerable promise.

PMID- 23974553
TI  - Why Medical Informatics (still) Needs Cognitive and Social Sciences.
AB  - OBJECTIVES: To summarize current excellent medical informatics research in the
      field of human factors and organizational issues. METHODS: Using PubMed, a total
      of 3,024 papers were selected from 17 journals. The papers were evaluated on the
      basis of their title, keywords, and abstract, using several exclusion and
      inclusion criteria. 15 preselected papers were carefully evaluated by six
      referees using a standard evaluation grid. RESULTS: Six best papers were selected
      exemplifying the central role cognitive and social sciences can play in medical
      informatics research. Among other contributions, those studies: (i) make use of
      the distributed cognition paradigm to model and understand clinical care
      situations; (ii) take into account organizational issues to analyse the impact of
      HIT on information exchange and coordination processes; (iii) illustrate how
      models and empirical data from cognitive psychology can be used in medical
      informatics; and (iv) highlight the need of qualitative studies to analyze the
      unexpected side effects of HIT on cognitive and work processes. CONCLUSION: The
      selected papers demonstrate that paradigms, methodologies, models, and results
      from cognitive and social sciences can help to bridge the gap between HIT and end
      users, and contribute to limit adoption failures that are reported regularly.

PMID- 23974554
TI  - A review of the empirical evidence of the healthcare benefits of personal health
      records.
AB  - OBJECTIVES: This literature review sought to identify the established evidence of
      the health and healthcare benefits (or harms) from the use of electronic personal
      health records (PHRs) and PHR systems. METHODS: The definition of a PHR published
      in ISO 14292 was used to scope this review and the search strategy. Publications
      were included if the introduction of a PHR was the primary intervention, and if
      its evaluation met one of the Cochrane EPOC Group criteria. Studies were excluded
      if they only reported the design or basic user acceptance of a PHR system without
      an assessment of its impact on individuals and/or their health care. The impacts
      were classified according to the six aims of 21st-century health care defined by
      the US Institute of Medicine. RESULTS: Searches were conducted in PubMed in
      December 2012. Out of 741 papers that met our initial search criteria, 31 were
      retained after title and abstract screening. After full paper review 5 studies
      were found to report original evidence of impact. Of these, three reported
      beneficial impacts on effectiveness, one on patient centredness, and one study
      reported impact on both aims. No harmful effects were reported. CONCLUSIONS:
      Although this literature review did identify some evidenced benefits from the use
      of PHRs and systems, our main observation is that there are very few studies
      published that seek to formally evaluate impact. The majority of publications we
      screened documented designs or basic user acceptance. Further investment in
      evaluation is needed to inform the evolution of this field.

PMID- 23974555
TI  - eHealth in North America.
AB  - OBJECTIVE: The overall objective of this paper is to provide an overview of the
      current status of electronic health record (EHR) adoption and implementation in
      Canada and the United States. METHODS: A review and synthesis of the empirical
      and grey literature about adoption of electronic health records in Canada and the
      United States was undertaken. RESULTS: Both Canada and the United States have
      experienced increases in their adoption rates. More specifically, 2012 adoption
      statistics reveal that the electronic medical record adoption rate in the United
      States is 69% and in Canada it is 57%. Significant investment by both governments
      has increased adoption of electronic records across North America. CONCLUSIONS:
      In the United States and Canada there has been a significant rise in the adoption
      of electronic records by health professionals with the aid of national government
      incentive programs.

PMID- 23974556
TI  - Use of Open Source Software in Health Care Delivery - Results of a Qualitative
      Field Study. Contribution of the EFMI LIFOSS Working Group.
AB  - OBJECTIVES: To assess and analyze the attitude of health IT executives towards
      the utilization of specialized medical Open Source software (OSS) in Germany's
      and other European countries' health care delivery. METHODS: After an initial
      literature review a field study was carried out based on semi-structured expert
      interviews. Eight German and 11 other European health IT executives were
      surveyed. The results were qualitatively analyzed using the grounded theory
      approach. Identified concepts were reviewed using SWOT analysis. RESULTS: In
      total, 13 strengths, 11 weaknesses, 3 opportunities, and 8 threats of the
      utilization of OSS in a clinical setting could be identified. Additionally,
      closely related aspects like general software procurement criteria, the overall
      attitude of health IT executives, users, and management towards OSS and its
      current and future use could as well be assessed. CONCLUSIONS: Medical OSS is
      rarely used in health care delivery. In order to capitalize the unique advantages
      of OSS in a clinical setting, complex requirements need to be addressed.
      Shortcomings of OSS describe an attractive breeding ground for new commercial
      offerings and services that need yet to be seen.

PMID- 23974557
TI  - Health Information Systems. Toward Evidence-based Health Information Systems?
AB  - OBJECTIVES: Summarize excellent current research in the field of Health
      Information Systems. METHOD: Synopsis of the articles selected for the IMIA
      Yearbook 2013. RESULTS: Five papers from international peer reviewed journals
      have been selected for the section on health information systems. CONCLUSIONS:
      The selected articles illustrate current research regarding health information
      technology (IT) impacts and evaluation and the latest developments in health
      information exchange.

PMID- 23974558
TI  - Sensor, signal, and imaging informatics: evidence-based health informatics.
AB  - OBJECTIVES: This synopsis presents a selection for the IMIA (International
      Medical Informatics Association) Yearbook 2013 of excellent research in the broad
      field of Sensor, Signal, and Imaging Informatics published in the year 2012.
      METHODS: We performed a systematic initial selection and a double blind peer
      review process to find the best papers in this domain published in 2012, from the
      PubMed and Web of Science databases. A set of MeSH keywords provided by experts
      was used. RESULTS: Current research in the field of sensor signal and imaging
      informatics is based on innovative sensors from which relevant information
      (signal and imaging) can be acquired and integrated into workflow based or
      patient based models. This rich environment can help the medical staff in
      carrying out more optimal care. The demonstration of the added value of such
      innovations is more and more performed through evidence-based evaluations.
      CONCLUSIONS: The best paper selection of articles on sensors, signal, and imaging
      informatics illustrates the wide spectrum covered by this field in 2012, and the
      attention paid to evaluations.

PMID- 23974559
TI  - Evidence-based clinical decision support.
AB  - BACKGROUND: Clinical decision support (CDS) is a key tool for enabling evidence
      based medicine and improving the quality of healthcare. However, effective CDS
      faces a variety of challenges, including those relating to knowledge synthesis,
      capture, transformation, localization and maintenance. If not properly addressed,
      these challenges can limit the effectiveness of CDS, and potentially risk
      inaccurate or inappropriate interventions to clinicians. OBJECTIVES: (1) To
      describe an approach to CDS development using evidence as a basis for clinical
      decision support systems that promote effective care; (2) To review recent
      evidence regarding the effectiveness of selected clinical decision support
      systems. METHOD: Review and analysis of recent literature with identification of
      trends and best practices. RESULTS: The state-of-the-art in CDS has advanced
      significantly, and many recent trials have shown CDS to be effective, although
      the results are mixed overall. Issues related to knowledge capture and synthesis,
      problems in knowledge transformation at the interface between knowledge authors
      and CDS developers, and problems specific to local CDS design and implementation
      can interfere with CDS development. Best practices, tools and techniques to
      manage them are described. CONCLUSIONS: CDS, when used well, can be effective,
      but further research is needed for it to reach its full potential.

PMID- 23974560
TI  - A medical informatics perspective on clinical decision support systems. Findings
      from the yearbook 2013 section on decision support.
AB  - OBJECTIVE: To summarize excellent research and to select best papers published in
      2012 in the field of computer-based decision support in healthcare. METHODS: A
      bibliographic search focused on clinical decision support systems (CDSSs) and
      computer provider order entry was performed, followed by a double-blind
      literature review. RESULTS: The review process yielded six papers, illustrating
      various aspects of clinical decision support. The first paper is a systematic
      review of CDSS intervention trials in real settings, and considers different
      types of possible outcomes. It emphasizes the heterogeneity of studies and
      confirms that CDSSs can improve process measures but that evidence lacks for
      other types of outcomes, especially clinical or economic. Four other papers
      tackle the safety of drug prescribing and show that CDSSs can be efficient in
      reducing prescription errors. The sixth paper exemplifies the growing role of
      ontological resources which can be used for several applications including
      decision support. CONCLUSIONS: CDSS research has to be continuously developed and
      assessed. The wide variety of systems and of interventions limits the
      understanding of factors of success of CDSS implementations. A standardization in
      the characterization of CDSSs and of intervention trial reporting will help to
      overcome this obstacle.

PMID- 23974561
TI  - Formal ontologies in biomedical knowledge representation.
AB  - OBJECTIVES: Medical decision support and other intelligent applications in the
      life sciences depend on increasing amounts of digital information. Knowledge
      bases as well as formal ontologies are being used to organize biomedical
      knowledge and data. However, these two kinds of artefacts are not always clearly
      distinguished. Whereas the popular RDF(S) standard provides an intuitive triple
      based representation, it is semantically weak. Description logics based ontology
      languages like OWL-DL carry a clear-cut semantics, but they are computationally
      expensive, and they are often misinterpreted to encode all kinds of statements,
      including those which are not ontological. METHOD: We distinguish four kinds of
      statements needed to comprehensively represent domain knowledge: universal
      statements, terminological statements, statements about particulars and
      contingent statements. We argue that the task of formal ontologies is solely to
      represent universal statements, while the non-ontological kinds of statements can
      nevertheless be connected with ontological representations. To illustrate these
      four types of representations, we use a running example from parasitology.
      RESULTS: We finally formulate recommendations for semantically adequate
      ontologies that can efficiently be used as a stable framework for more context
      dependent biomedical knowledge representation and reasoning applications like
      clinical decision support systems.

PMID- 23974563
TI  - Knowledge representation and management: towards an integration of a semantic web
      in daily health practice.
AB  - OBJECTIVE: To summarize the best papers in the field of Knowledge Representation
      and Management (KRM). METHODS: A synopsis of the four selected articles for the
      IMIA Yearbook 2013 KRM section is provided, as well as highlights of current KRM
      trends, in particular, of the semantic web in daily health practice. The manual
      selection was performed in three stages: first a set of 3,106 articles, then a
      second set of 86 articles followed by a third set of 15 articles, and finally the
      last set of four chosen articles. RESULTS: Among the four selected articles (see
      Table 1), one focuses on knowledge engineering to prevent adverse drug events;
      the objective of the second is to propose mappings between clinical archetypes
      and SNOMED CT in the context of clinical practice; the third presents an ontology
      to create a question-answering system; the fourth describes a biomonitoring
      network based on semantic web technologies. CONCLUSION: These four articles
      clearly indicate that the health semantic web has become a part of daily practice
      of health professionals since 2012. In the review of the second set of 86
      articles, the same topics included in the previous IMIA yearbook remain active
      research fields: Knowledge extraction, automatic indexing, information retrieval,
      natural language processing, management of health terminologies and ontologies.

PMID- 23974562
TI  - The Evidence-base for Using Ontologies and Semantic Integration Methodologies to
      Support Integrated Chronic Disease Management in Primary and Ambulatory Care:
      Realist Review. Contribution of the IMIA Primary Health Care Informatics WG.
AB  - BACKGROUND: Most chronic diseases are managed in primary and ambulatory care. The
      chronic care model (CCM) suggests a wide range of community, technological, team
      and patient factors contribute to effective chronic disease management.
      Ontologies have the capability to enable formalised linkage of heterogeneous data
      sources as might be found across the elements of the CCM. OBJECTIVE: To describe
      the evidence base for using ontologies and other semantic integration methods to
      support chronic disease management. METHOD: We reviewed the evidence-base for the
      use of ontologies and other semantic integration methods within and across the
      elements of the CCM. We report them using a realist review describing the context
      in which the mechanism was applied, and any outcome measures. RESULTS: Most
      evidence was descriptive with an almost complete absence of empirical research
      and important gaps in the evidence-base. We found some use of ontologies and
      semantic integration methods for community support of the medical home and for
      care in the community. Ubiquitous information technology (IT) and other IT tools
      were deployed to support self-management support, use of shared registries,
      health behavioural models and knowledge discovery tools to improve delivery
      system design. Data quality issues restricted the use of clinical data; however
      there was an increased use of interoperable data and health system integration.
      CONCLUSIONS: Ontologies and semantic integration methods are emergent with
      limited evidence-base for their implementation. However, they have the potential
      to integrate the disparate community wide data sources to provide the information
      necessary for effective chronic disease management.

PMID- 23974564
TI  - Personal health and consumer informatics. The impact of health oriented social
      media applications on health outcomes.
AB  - OBJECTIVES: The rapid evolution in the world-wide use of Social Media tools
      suggests the emergence of a global phenomenon that may have implications in the
      Personal Health and Consumer Health Informatics domains. However the impact of
      these tools on health outcomes is not known. The goal of this research was to
      review the randomized controlled trial (RCT) evidence of the impact of health
      oriented Social Media informatics tools on health outcomes. METHODS: Evaluations
      of Social Media consumer health tools were systematically reviewed. Research was
      limited to studies published in the English language, published in Medline,
      published in the calendar year 2012 and limited to studies that utilized a RCT
      methodological design. RESULTS AND CONCLUSIONS: Two high quality Randomized
      Controlled Trials among over 600 articles published in Medline were identified.
      These studies indicate that Social Media interventions may be able to
      significantly improve pain control among patients with chronic pain and enhance
      weight loss maintenance among individuals attempting to lose weight.
      Significantly more research needs to be done to confirm these early findings,
      evaluate additional health outcomes and further evaluate emerging health oriented
      Social Media interventions. Chronic pain and weight control have both socially
      oriented determinants. These studies suggest that understanding the social
      component of a disease may ultimately provide novel therapeutic targets and socio
      clinical interventional strategies.

PMID- 23974565
TI  - Social Media for the Promotion of Holistic Self-Participatory Care: An Evidence
      Based Approach. Contribution of the IMIA Social Media Working Group.
AB  - OBJECTIVES: As health information is becoming increasingly accessible, social
      media offers ample opportunities to track, be informed, share and promote health.
      These authors explore how social media and holistic care may work together; more
      specifically however, our objective is to document, from different perspectives,
      how social networks have impacted, supported and helped sustain holistic self
      participatory care. METHODS: A literature review was performed to investigate the
      use of social media for promoting health in general and complementary alternative
      care. We also explore a case study of an intervention for improving the health of
      Greek senior citizens through digital and other means. RESULTS: The Health Belief
      Model provides a framework for assessing the benefits of social media
      interventions in promoting comprehensive participatory self-care. Some
      interventions are particularly effective when integrating social media with real
      world encounters. Yet not all social media tools are evidence-based and
      efficacious. Interestingly, social media is also used to elicit patient ratings
      of treatments (e.g., for depression), often demonstrating the effectiveness of
      complementary treatments, such as yoga and mindfulness meditation. CONCLUSIONS:
      To facilitate the use of social media for the promotion of complementary
      alternative medicine through self-quantification, social connectedness and
      sharing of experiences, exploration of concrete and abstract ideas are presented
      here within. The main mechanisms by which social support may help improve health 
      emotional support, an ability to share experiences, and non-hierarchal roles,
      emphasizing reciprocity in giving and receiving support - are integral to social
      media and provide great hope for its effective use.

PMID- 23974566
TI  - Evidence-based Practice. Findings from the Section on Education and Consumer
      Health Informatics.
AB  - OBJECTIVES: To provide an overview of outstanding current research conducted in
      Education and Consumer Informatics. METHOD: Synopsis of the articles on education
      and consumer health informatics published in 2012 and selected for the IMIA
      Yearbook of Medical Informatics 2013. RESULTS: Architecture of monitoring or
      telehealth information systems for patients with chronic disease must include
      wireless devices to aid in the collection of personal data. Data acquisition
      technologies have an impact on patients' willingness to participate in telehealth
      programmes. Patients are more likely to prefer mobile applications over web-based
      applications. Social media is widely used by clinicians. Especially younger
      clinicians use it for personal purposes and for reference materials retrieval.
      Questions remain on optimal training requirements and on the effects on clinician
      behavior and on patient outcomes. A high level of e-Health literacy by patients
      will promote increased adoption and utilization of personal health records.
      CONCLUSION: The selected articles highlight the need for training of clinicians
      to become aware of existing telehealth systems, in order to correctly inform and
      guide patients to take part in telehealth systems and adopt personal healthcare
      records (PHR).

PMID- 23974567
TI  - Bringing genome tests into clinical practice.
AB  - OBJECTIVE: To provide a review of recent progress in the use of genomic data in
      clinical contexts. METHOD: Survey of key articles selected from the previous year
      (2012). RESULT: Two major themes emerged as areas of focus in 2012: (1)
      integration of genomic data into electronic health records; and (2) determining
      the clinical utility of genomic tests. CONCLUSION: Significant advances are being
      made towards the integration of genomic data such that they may useful for
      clinical decision making. While the short term advances will likely still be seen
      in clinically valid genotype-phenotype research, there have been promising
      advances towards developing genomic tests that may be of clinical utility in the
      near future.

PMID- 23974568
TI  - From genome sequencing to bedside. Findings from the section on bioinformatics
      and translational informatics.
AB  - OBJECTIVES: To summarize excellent current research in the field of
      Bioinformatics and Translational Informatics with application in the health
      domain and evidence-based medicine. METHOD: We provide a synopsis of the articles
      selected for the IMIA Yearbook 2013, from which we attempt to derive a synthetic
      overview of current and future activities in the field. Three steps of selection
      were performed by querying PubMed and Web of Science. A first set of 5,549
      articles was refined into a second set of 1,272 articles from which 15 articles
      were retained for peer-review. RESULTS: The selection and evaluation process of
      this Yearbook's section on Bioinformatics and Translational Informatics yielded
      four excellent articles regarding the Human Genome and Medicine. Exploiting
      genomic data depends on having the appropriate reference annotation available. In
      the first article, the goal of the GENCODE Consortium is to produce and publish
      The GENCODE human reference gene set. As a result it is composed by merged manual
      and automatic annotations, which are frequently updated from public experimental
      databases. The quality of genome sequencing is platform-dependant. In the second
      article, a generic database independent from the sequencing technologies,
      Huvariome, can help to identify errors and inconsistencies in sequencing. To
      understand complex diseases of patients it will be of great importance to detect
      rare gene variants. This is the aim of the third study. Finally, in the last
      article, the plasma's DNA of healthy individual and patients suffering from
      cancer is compared. CONCLUSIONS: The current research activities attest to the
      continuous convergence of Bioinformatics and Medical Informatics for clinical
      practice. For instance, a direct use of high throughput sequencing technologies
      for patients could aid the diagnosis of complex diseases (such as cancer) without
      invasive surgery (such as biopsy) but only with blood analysis. However, ongoing
      genomic tests will generate massive amounts of data and will imply new trends in
      the near future: "Big Data" and smart health management.

PMID- 23974569
TI  - Clinical research informatics: survey of recent advances and trends in a maturing
      field.
AB  - OBJECTIVES: To provide a survey of the field of clinical research informatics
      (CRI), focusing in particular on significant developments over the past 3 years
      and the insights they provide about the progress and state of the field. METHODS:
      An iterative "scoping review" of the literature published in scientific journals
      and conference proceedings that are relevant to CRI, from late 2009 to early
      2013. RESULTS: 212 articles were identified, and 64 were selected to illustrate
      recent advances in the field. Based on those, six categories of CRI activity were
      identified: Data and Knowledge Management, Discovery and Standards; Clinical Data
      Re-Use for Research; Researcher Support and Resources; Participant Recruitment;
      Patients/Consumers and CRI; Policy, Regulatory and Fiscal Matters. CONCLUSIONS:
      This survey demonstrates that the field of CRI has matured and is now well
      established. The ongoing work is essential to overcome many of the challenges the
      clinical research enterprise is facing and more work is needed. Even as work
      continues to establish necessary infrastructure, methods, and best practices, CRI
      researchers should strive for more rigorous study designs to evaluate the impacts
      of the work in the field. There is little doubt that the field is poised for
      rapid growth, and that the CRI literature will continue to reflect that growth in
      years to come.

PMID- 23974570
TI  - Information technology for clinical, translational and comparative effectiveness
      research. Findings from the section clinical research informatics.
AB  - OBJECTIVES: To summarize advances of excellent current research in the new
      emerging field of Clinical Research Informatics. METHOD: Synopsis of four key
      articles selected for the IMIA Yearbook 2013. The selection was performed by
      querying PubMed and Web of Science with predefined keywords. From the original
      set of 590 papers, a first subset of 461 articles which was in the scope of
      Clinical Research Informatics was refined into a second subset of 79 relevant
      articles from which 15 articles were retained for peer-review. RESULTS: The four
      selected articles exemplify current research efforts conducted in the areas of
      data representation and management in clinical trials, secondary use of EHR data
      for clinical research, information technology platforms for translational and
      comparative effectiveness research and implementation of privacy control.
      CONCLUSIONS: The selected articles not only illustrate how innovative information
      technology supports classically organized randomized controlled trials but also
      demonstrate that the long promised benefits of electronic health care data for
      research are becoming a reality through concrete platforms and projects.

PMID- 23974571
TI  - Medical informatics in morocco.
AB  - OBJECTIVES: Informatics is an essential tool for helping to transform healthcare
      from a paper-based to a digital sector. This article explores the state-of-the
      art of health informatics in Morocco. Specifically, it aims to give a general
      overview of the Moroccan healthcare system, the challenges it is facing, and the
      efforts undertaken by the informatics community and Moroccan government in terms
      of education, research and practice to reform the country's health sector.
      METHODS: Through the experience of establishing Medical Informatics as a medical
      specialty in 2008, creating a Moroccan Medical Informatics Association in 2010
      and holding a first national congress took place in April 2012, the authors
      present their assessment of some important priorities for health informatics in
      Morocco. RESULTS: These Moroccan initiatives are facilitating collaboration in
      education, research, and implementation of clinical information systems. In
      particular, the stakeholders have recognized the need for a national coordinator
      office and the development of a national framework for standards and
      interoperability. CONCLUSION: For developing countries like Morocco, new health
      IT approaches like mobile health and trans-media health advertising could help
      optimize scarce resources, improve access to rural areas and focus on the most
      prevalent health problems, optimizing health care access, quality, and cost for
      Morocco population.

PMID- 23974572
TI  - Two Decades of HELINA Conferences: A Historical Review of Health Informatics in
      Africa.
AB  - OBJECTIVE: Review the history of health informatics in Africa as projected by the
      HELINA conferences, to draw inferences for the next phase. METHODS AND MATERIALS:
      Summarising from the proceedings of HELINA 93, unpublished programmes and reports
      of later conferences, abstracts and presentations on the web sites of the most
      recent conferences, and personal recollections of all but one of the conferences.
      Analysing the e-health situation in Africa in 1993, 2007 and 2011 by mapping
      software applications presented in the respective conferences on a simplified
      model of potential spots for e-health use. RESULTS: The following phases were
      identified: Pre-phase from 1979; individual scientific papers. Phase 1, the 1993
      1999 conferences; carried by the momentum of HELINA 93. Phase 2, interregnum;
      difficulty to find conference organisers. Phase 3, the 2007-2011 conferences;
      carried by the HELINA association as IMIA Africa Region. Currently most of the
      important spots for e-health use are being populated by appropriate software
      applications, mostly by collaborative open source projects. Phase 4 starting,
      characterised by the expansion of e-health practice on the continent, the HELINA
      association as a key organiser, and annual HELINA conferences becoming
      scientifically stronger and more visible. CONCLUSIONS: Key issues in making
      health informatics blossom in Africa include local development capacity,
      community orientation, collaborative design, international collaboration,
      government support, champions and organised continent-wide collaboration.

PMID- 23974573
TI  - Medical decision support and medical informatics education: roots, methods and
      applications in czechoslovakia and the czech republic.
AB  - The paper describes the history of medical informatics in Czechoslovakia and the
      Czech Republic. It focuses on the topics of medical informatics education and
      decision support methods and systems. Several conferences held in Czechoslovakia
      and in the Czech Republic organized in cooperation with IMIA or EFMI are
      described. Support of European Union and Czech agencies in several European and
      national projects focused on medical informatics topics highly contributed to
      medical informatics development in Czechoslovakia and the Czech Republic and to
      the establishment of the European Center for Medical Informatics, Statistics and
      Epidemiology as the joint workplace of Charles University in Prague and Academy
      of Sciences of the Czech Republic in 1994. 

PMID- 23974574
TI  - Examining health information-seeking behaviors of older adults.
AB  - This study aims to examine which resources older adults utilize for their health
      information needs, how trustworthy and reliable they find these resources, and
      the difficulties they face in obtaining health-related information. A 41-item
      survey designed to understand the information-seeking characteristics of older
      adults was developed and distributed to retirement communities. Some items were
      taken from the Health Information National Trends Survey. Of 1520 surveys, 403
      were returned completed (26.6%). Respondents' mean age was 77.65 years. Average
      scores indicated respondents trusted particular sources of health information in
      the following order (highest to lowest): health care providers, pharmacists,
      friends and relatives, retirement community staff, newspapers, the Internet,
      television, and the radio. In conclusion, older adults have a greater amount of
      trust in a person with whom they are able to actively discuss their health as
      opposed to a nonliving source, which they have to access or manipulate, such as
      the Internet. Efforts must be made to help older adults better navigate and
      utilize the Internet and recognize dependable online sources so that they may
      increase their trust in its use, thereby increasing satisfaction with their own
      ability to seek and use sources of health information. 

PMID- 23974575
TI  - Alopecia areata: an update.
AB  - Alopecia areata (AA) is a common form of non-scarring hair loss of scalp and/or
      body. Genetic predisposition, autoimmunity, and environmental factors play a
      major role in the etiopathogenesis of AA. Patchy AA is the most common form.
      Atopy and autoimmune thyroiditis are most common associated conditions.
      Peribulbar and intrabulbar lymphocytic inflammatory infiltrate resembling "swarm
      of bees" is characteristic on histopathology. Treatment is mainly focused to
      contain the disease activity. Corticosteroids are the preferred treatments in
      form of topical, intralesional, or systemic therapy. Camouflage in the form of
      wigs may be an alternative option in refractory cases. 

PMID- 23974576
TI  - What's new in cicatricial alopecia?
AB  - Scalp hairs complete the body self-image and patients with alopecia suffer from
      overt disfiguration, leading to psychosocial embarrassment and significant lack
      of self-esteem. Hence an early diagnosis and an aggressive treatment in the case
      of active hair loss are crucial in the management of scarring alopecia. This
      review presents a comprehensive study of newer theories in aetiopathogenesis,
      evolving diagnostic modalities and a step ladder approach in management of
      primary cicatricial alopecia. 

PMID- 23974577
TI  - Telogen effluvium.
AB  - Telogen effluvium (TE) is one of the most common causes of diffuse nonscarring
      hair loss. In its acute form, it generates a lot of anxiety in the patient, which
      can be significantly allayed with a confident diagnosis. In its more chronic
      form, however, the hair loss may go unnoticed for long periods of time. Here in,
      the dermatologist's role in differentiating it from the more common patterned
      hair loss is significant. Differentiating TE from other causes of diffuse
      nonscarring hair loss can indeed be a daunting task and TE is often used as a
      waste basket diagnosis. A number of factors have been implicated in the causation
      of TE, however, clear evidence in their support is lacking. The role of stress as
      a causative factor as well as the result of hair loss needs to be adequately
      understood. This review aims at summarizing our current level of knowledge with
      respect to this very common cause of hair loss. An attempt is made to help the
      readers reliably differentiate TE from other causes of diffuse nonscarring hair
      loss. The possible causative factors, pathogenetic mechanisms, clinical
      presentation, and possible treatment options are discussed. 

PMID- 23974578
TI  - Anagen effluvium.
AB  - Disturbances of hair follicle cycling lie at the heart of most hair growth
      disorders, and have dramatic effects on visible hair growth and shedding. The two
      common disorders due to aberration in hair follicle cycling are telogen and
      anagen effluvium. Though a lot of literature addresses the problem of telogen
      effluvium, there are not many reviews on anagen effluvium or anagen hair loss.
      Anagen effluvium is considered synonymous with chemotherapy-induced alopecia and
      other causes are rarely considered. In this review, we try to discuss the
      etiopathogenesis, clinical presentation, differentials, and management issues in
      anagen effluvium. Anagen effluvium is the abrupt loss of hairs that are in their
      growing phase (anagen) due to an event that impairs the mitotic or metabolic
      activity of hair follicle. Chemotherapy, radiation and toxic chemicals, and
      sometimes inflammatory diseases like alopecia areata and pemphigus are also
      capable of diminishing the metabolic activity of hair follicles resulting in
      anagen hair loss. Although it is reversible, and hair regrowth occurs after a
      delay of 1-3 months; sometimes it can lead to permanent alopecia and can be
      psychologically devastating with negative impact on individual perceptions of
      appearance, body image, sexuality, and self-esteem. For some patients, the
      emotional trauma may be so severe that it may lead to discontinuing or refusing
      therapy that might otherwise be beneficial. In such cases, a psychosomatic
      approach as well as empathic consideration of the patients concerns and fears as
      well as the provision of practical medical-aesthetic and styling tips are equally
      important and can be integrated in management. 

PMID- 23974579
TI  - Androgenetic alopecia: an update.
AB  - Androgenetic alopecia (AGA) is one of the commonest reasons for dermatological
      consultation. Over the last few years our understanding of the pathophysiology of
      AGA has improved and this has paved way for better diagnostic and therapeutic
      options. Recent research has dwelled on the role of stem cells in the
      pathophysiology of AGA and has also identified newer genetic basis for the
      condition. Dermoscopy/trichoscopy has emerged as a useful diagnostic tool for
      AGA. While the major treatment options continue to be topical minoxidil, systemic
      Finasteride and hair transplantations, newer modalities are under investigation.
      Specific diagnostic and treatment recommendations have also been developed on
      evidence based principles. This article reviews the recent concepts in relation
      to AGA. With regards to the pathophysiology we have tried to stress on recent
      knowledge of the molecular and genetic basis of AGA. We have emphasized on an
      evidence based approach for treatment and diagnosis. 

PMID- 23974581
TI  - Premature graying of hair.
AB  - Premature graying is an important cause of low self-esteem, often interfering
      with socio-cultural adjustment. The onset and progression of graying or canities
      correlate very closely with chronological aging, and occur in varying degrees in
      all individuals eventually, regardless of gender or race. Premature canities may
      occur alone as an autosomal dominant condition or in association with various
      autoimmune or premature aging syndromes. It needs to be differentiated from
      various genetic hypomelanotic hair disorders. Reduction in melanogenically active
      melanocytes in the hair bulb of gray anagen hair follicles with resultant pigment
      loss is central to the pathogenesis of graying. Defective melanosomal transfers
      to cortical keratinocytes and melanin incontinence due to melanocyte degeneration
      are also believed to contribute to this. The white color of canities is an
      optical effect; the reflection of incident light masks the intrinsic pale yellow
      color of hair keratin. Full range of color from normal to white can be seen both
      along individual hair and from hair to hair, and admixture of pigmented and white
      hair is believed to give the appearance of gray. Graying of hair is usually
      progressive and permanent, but there are occasional reports of spontaneous
      repigmentation of gray hair. Studies evaluating the association of canities with
      osteopenia and cardiovascular disease have revealed mixed results. Despite the
      extensive molecular research being carried out to understand the pathogenesis of
      canities, there is paucity of effective evidence-based treatment options. Reports
      of repigmentation of previously white hair following certain inflammatory
      processes and use of drugs have suggested the possibility of cytokine-induced
      recruitment of outer sheath melanocytes to the hair bulb and rekindled the hope
      for finding an effective drug for treatment of premature canities. In the end,
      camouflage techniques using hair colorants are outlined. 

PMID- 23974580
TI  - Female pattern hair loss.
AB  - Female pattern hair loss (FPHL) is a common cause of hair loss in women
      characterized by diffuse reduction in hair density over the crown and frontal
      scalp with retention of the frontal hairline. Its prevalence increases with
      advancing age and is associated with significant psychological morbidity. The
      pathophysiology of FPHL is still not completely understood and seems to be
      multifactorial. Although androgens have been implicated, the involvement of
      androgen-independent mechanisms is evident from frequent lack of clinical or
      biochemical markers of hyperandrogenism in affected women. The role of genetic
      polymorphisms involving the androgen and estrogen receptors is being increasingly
      recognized in its causation and predicting treatment response to anti-androgens.
      There are different clinical patterns and classifications of FPHL, knowledge of
      which facilitates patient management and research. Chronic telogen effluvium
      remains as the most important differential diagnosis. Thorough history, clinical
      examination, and evaluation are essential to confirm diagnosis. Patients with
      clinical signs of androgen excess require assessment of biochemical parameters
      and imaging studies. It is prudent to screen the patients for metabolic syndrome
      and cardiovascular risk factors. The treatment comprises medical and/or surgical
      modalities. Medical treatment should be initiated early as it effectively arrests
      hair loss progression rather than stimulating regrowth. Minoxidil continues to be
      the first line therapy whereas anti-androgens form the second line of treatment.
      The progressive nature of FPHL mandates long-term treatment for sustained effect.
      Medical therapy may be supplemented with cosmetic concealment in those desirous
      of greater hair density. Surgery may be worthwhile in some carefully selected
      patients. 

PMID- 23974582
TI  - Hair cosmetics.
AB  - The hair cosmetic industry has undergone a revolutionary change over the last two
      decades. The focus has dramatically veered from merely cleaning to repair,
      increasing the tensile strength, reducing oxidative damage, and stimulating
      growth. Newer shorter procedures to make hair look naturally more lustrous,
      smooth, and manageable have evolved. Specialized grooming products have been
      formulated to cleanse, calm, and condition the hair, and are tailored for
      different hair-types, for example, dry, dry-damaged, oily, colored, and gray
      hair. Other products are formulated to alter the color or structure of the hair
      shaft, for example, hair dyes, perming/relaxing. Hair sprays and waxes/gels, can
      alter the 'lift' of the hair-shaft. Although dermatologists are experts in
      managing scalp and hair diseases, the esthetic applications of newer cosmetic
      therapies still remain elusive. This article attempts to fill the lacunae in our
      knowledge of hair cosmetics and esthetic procedures relevant in today's rapidly
      changing beauty-enhancing industry, with special emphasis on the Indian scenario
      for chemical and 'natural' hair products. 

PMID- 23974583
TI  - A longitudinal study of consistency in diagnostic accuracy of teledermatology
      tools.
AB  - BACKGROUND: Diagnostic accuracy (DA) is an outcome measure to assess the
      feasibility of teledermatology tools. Despite ample data with variable DA values,
      no study has examined the aggregate DA value obtained from the available studies
      and observed its consistency over a period of time. This kind of a longitudinal
      study about teledermatology will be necessary to check its usefulness and plan
      for further implementation. AIMS: To observe the DA trend over a period of 15
      years (1997-2011). METHODS: Only those studies (n = 59) using a single tool for
      general, tertiary, and subspecialty teledermatology practice were included to
      obtain the DA values. Studies were graded based on the number of subjects and
      gold standard comparison between teledermatologist and clinical dermatologist
      (face-to-face examination). RESULTS: This analysis sought to identify the DA
      trend was carried out by evaluating 17 store and forward teledermatology (SAFT)
      based and 8 Video conference (VC) tool-based studies with 2385 and 1305 patients
      respectively, in comparison with the gold-standard assessment. The average DA was
      73.35% +/- 14.87% for SAFT and 70.37% +/- 7.01% for VC. One sample t-test
      analysis with 100% accuracy as standard value revealed 28% deficiency for SAFT (t
      = 7.925; P = 0.000) and 30% deficiency for VC (t = 11.955; P = 0.000). Kruskall
      Wallis test confirmed the consistency of DA values in the SAFT (chi2 = 1.852, P =
      0.763) tool. CONCLUSION: SAFT and VC were adequately validated on a large number
      of patients by various feasibility studies with the gold standard (face-to-face)
      comparison between teledermatologists and clinical dermatologists. The DA of SAFT
      was good, stable over the 15 years and comparable to VC. Health-care providers
      need to plan for appropriate utility of SAFT either alone or in combination with
      VC to implement and deliver teledermatology care in India.

PMID- 23974584
TI  - The psychosocial impact of vitiligo in Indian patients.
AB  - BACKGROUND: Vitiligo has a special significance in Indian patients both because
      depigmentation is obvious on darker skin and the enormous stigma associated with
      the disease in the culture. AIMS: This study was carried out to determine the
      beliefs about causation, aspects of the disease that cause concern, medical, and
      psychosocial needs of the patients, expectation from treatment and from the
      treating physician, and effects of disease on the patient's life. METHODS: Semi
      structured interviews were conducted in 50 patients with vitiligo. Purposive
      sampling was used to select subjects for the study. Each interview was recorded
      on an audio-cassette and transcripts were analyzed to identify significant issues
      and concerns. RESULTS: Patients had a range of concerns regarding their disease
      such as physical appearance, progression of white patches onto exposed skin and
      the whole body, ostracism, social restriction, dietary restrictions, difficulty
      in getting jobs, and they considered it to be a significant barrier to getting
      married. The condition was perceived to be a serious illness. Stigma and suicidal
      ideation was reported. While there were several misconceptions about the cause of
      vitiligo, most patients did not think their disease was contagious, heritable or
      related to leprosy. Multiple medical consultations were frequent. Complete
      repigmentation was strongly desired, but a lesser degree of repigmentation was
      acceptable if progression of disease could be arrested. The problems were
      perceived to be more severe in women. The disease imposed a significant financial
      burden. CONCLUSION: Addressing psychosocial factors is an important aspect of the
      management of vitiligo, particularly in patients from communities where the
      disease is greatly stigmatizing.

PMID- 23974585
TI  - Cyclosporine in Stevens Johnson syndrome and toxic epidermal necrolysis and
      retrospective comparison with systemic corticosteroid.
AB  - BACKGROUND: Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
      are life-threatening dermatological emergencies. Many immunosuppressive
      modalities have been tried with variable results. AIMS: To determine the efficacy
      of cyclosporine in cases of SJS and TEN and compare the efficacy with systemic
      corticosteroid in the same condition. METHODS: Study was conducted at a tertiary
      hospital during 01 July 2011 to 30 June 2012. SCORTEN was assessed at the time of
      admission. Total body surface area (TBSA) assessment was like any burn patients.
      Cyclosporine was administered in the dose of 3 mg/kg body weight in three divided
      dosage for 07 days and then tapered over another 07 days. Data were compared to a
      historical series of SJS/TEN patients, managed by systemic steroids a year ago.
      RESULTS: A total of 11 consecutive patients with a mean age of 32.09 and standard
      deviation (SD 16.17) were enrolled in to cyclosporine group, which were
      retrospectively compared to 6 patients with a mean age of 27.87 (SD 13.97) years
      in the corticosteroid group. The mean duration of re-epithelialization was 14.54
      (SD 4.08) and 23 days (SD 6.68) in cyclosporine and corticosteroid group
      respectively (P = 0.009956). Mean hospital stay was 18.09 (SD 5.02) and 26 (SD
      6.48) days in cyclosporine and corticosteroid group respectively (P = 0.02597). A
      total of 1.11 and 0.51 patients were expected to die against no death and two
      deaths in cyclosporine and corticosteroid group respectively (Standardized
      mortality ratio = 3.92) (P = 0.04321). CONCLUSION: This study definitely suggests
      that cyclosporine has encouraging role in the management of uncomplicated cases
      of SJS, SJS-TEN overlap or TEN.

PMID- 23974586
TI  - Fite-Faraco staining in combination with multiplex polymerase chain reaction: a
      new approach to leprosy diagnosis.
AB  - BACKGROUND: Leprosy is not always an easy disease to diagnose, and patients can
      remain undiagnosed for longtime, not only at the peripheral clinics but also even
      at places with higher medical facilities, so, there is an urgent need for rapid
      and definitive modalities for leprosy diagnosis. This prospective study evaluates
      the ability of Fite-Faraco staining (FF staining) and multiplex polymerase chain
      reaction (PCR) over hematoxylin and eosin staining (H and E staining) and Ziehl
      Neelsen staining (ZN staining). AIMS: The aim of this perspective study is to
      evaluate the effectiveness of FF staining in combination with multiplex PCR for
      the early and rapid diagnosis of leprosy than any other coexisting diagnosis
      tool. METHODS: Patients with new skin patches or nodules with or without evidence
      of nerve damage were selected for the study. Punch biopsy was collected according
      to standard procedures. Each biopsy sample was divided into two equal parts, one
      half was fixed in 4% (v/v) buffered neutral formalin and then accordingly
      embedded in paraffin. Sections were stained by three different methods: H and E
      staining for histopathological examination, ZN staining, and FF staining for
      detection of acid-fast bacilli (AFB). And the other part was subjected for DNA
      extraction and PCR was carried out by the obtained DNA sample. RESULTS: H and E
      staining, ZN staining, FF staining, and PCR yield 58.2%, 50.9%, 60%, and 67.7%
      successful diagnosis of leprosy. The true diagnostic performances for these
      techniques were as follows: H and E staining - sensitivity 70.6%, positive
      predictive value (PPV) 81.9%, negative predictive value (NPV) 53.6%. For ZN
      staining - sensitivity 59.9%, PPV 69%, NPV 45.7%. For FF staining - sensitivity
      74.6%, PPV 85.9%, NPV 56.7%, and for PCR - sensitivity 87.8%, PPV 95.6%, NPV
      71.2%. CONCLUSION: The combination of FF staining and PCR was shown to provide a
      rapid and definitive diagnosis in the majority of leprosy suspected cases with a
      higher positive likelihood ratio (+LR) of 7.76 and 2.716, respectively, than H
      and E staining of 2.244 and ZN staining of 1.378.

PMID- 23974587
TI  - Skin lightening agents - Use or abuse? - A retrospective analysis of the topical
      preparations used by melasma patients of darker skin types.

PMID- 23974588
TI  - Major precipitating factors for stigma among stigmatized vitiligo and psoriasis
      patients with brown-black skin shades.

PMID- 23974589
TI  - Role of polymerase chain reaction in detection of genital herpes.

PMID- 23974590
TI  - A retrospective study of mortality of pemphigus patients in a tertiary care
      hospital.

PMID- 23974591
TI  - Co-reactivation of varicella zoster virus and herpes simplex virus with
      disseminated cutaneous lesions in a lymphoma patient.

PMID- 23974592
TI  - Verrucous growth arising over hypertrophic lichen planus.

PMID- 23974593
TI  - Benign cephalic histiocytosis.

PMID- 23974594
TI  - Rubinstein-Taybi syndrome: a report of two siblings with unreported cutaneous
      stigmata.

PMID- 23974595
TI  - Familial Bowen's disease.

PMID- 23974596
TI  - Acquired bullous dermatosis associated with IgA multiple myeloma.

PMID- 23974597
TI  - Uses of hypodermic needle in dermatology.

PMID- 23974598
TI  - Study on reactivation of herpes family of viruses in cutaneous adverse drug
      reactions.

PMID- 23974599
TI  - Fibroepithelioma of Pinkus: a distinctive variant of trichoblastic carcinoma.

PMID- 23974600
TI  - Edema and ulcers on the legs and dilated abdominal veins caused by
      thromboembolism of inferior vena cava in a patient with protein C deficiency.

PMID- 23974601
TI  - Vohwinkel syndrome with mental retardation.

PMID- 23974602
TI  - Do you really know (or care) what areas of practice you do best and which you do
      less well?

PMID- 23974603
TI  - Commentary on Kramer et al. The incidence of ulnocarpal complaints after distal
      radial fracture in relation to the fracture of the ulnar styloid.

PMID- 23974604
TI  - Re: Werber et al. Biomechanical effect of isolated capitate shortening in
      Kienbock's disease: an anatomical study. J Hand Surg Eur. 2013, 38: 500-7.

PMID- 23974605
TI  - Re: Sierakowski A. and Elliot D. Amputation for pain in a thumb - not an
      advisable treatment. J Hand Surg Eur. 2013, 38: 331-3.

PMID- 23974607
TI  - Capnocytophaga canimorsus sepsis following BMT in a patient with AML: possible
      association with functional asplenia.

PMID- 23974608
TI  - Reovirus as a successful ex vivo purging modality for multiple myeloma.
AB  - Autologous stem cell rescue (ASCT) following high-dose myeloablative chemotherapy
      is considered to be a therapeutic option for many multiple myeloma (MM) patients;
      however relapse post ASCT presents a major challenge. The oncolytic potential of
      reovirus has been previously demonstrated and is currently undergoing phase I
      monotherapy clinical trials for MM and phase II/III clinical trials for solid
      tumors. Here we tested the hypothesis that reovirus can successfully purge MM in
      a murine model that partially recapitulates human MM. RPMI 8226, MM1S, H929 and
      U266 human myeloma cell lines were exposed to reovirus and oncolysis was
      assessed. Apheresis product admixed with MM cells was purged with live reovirus
      (LV) or dead virus (DV) and purging efficacy was monitored via flow cytometry,
      reverse transcribed-PCR (RT-PCR) and disease relapse in non obese diabetic/severe
      combined immune deficient (NOD/SCID) mice. Significant LV purging was seen with
      MM1S, H929 and U266 and the complete ex vivo purging achieved with RPMI 8226 was
      confirmed by flow cytometry, RT-PCR and absence of disease relapse in vivo. Mice
      that received LV-purged autografts exhibited 100% survival in comparison to mice
      that received DV-purged controls. Reovirus's unique ability to kill MM while
      sparing hematopoietic stem cells places it as an attractive purging agent for MM
      during ASCT. 

PMID- 23974609
TI  - Normal cognitive functioning in a patient with Hb Bart's hydrops successfully
      cured by hematopoietic SCT.

PMID- 23974610
TI  - Immune complexes of E. coli antigens and maternal IgG in the bursa of Fabricius.
AB  - The bursa of Fabricius of the chicken is known to be both a primary lymphoid
      organ and a secondary lymphoid tissue. Bursal follicles are equipped with antigen
      trapping follicle-associated epithelium. However, bioactive antigens such as
      protein and bacteria have not been detected in the bursal parenchyma. By
      immunoperoxidase staining with a polyspecific antibody (Ab) against Escherichia
      coli, we detected aggregated E. coli antigens in the medulla of bursal follicles
      after hatching. The distribution of aggregated E. coli antigens is restricted to
      the medulla of bursal follicles. The antigens are not found in the spleen or the
      parenchyma of the caecal tonsil. The bursa is thus a trapping site for E. coli
      antigens from the external environment. Furthermore, two-color immunostaining
      clarified that these antigens form immune complexes with maternal IgG (MIgG) and
      are retained by reticular cells. Additionally, immune complexes in the bursa were
      shown to induce the rapid development of serum IgM Ab for indigenous E. coli. Our
      results suggest that immune complexes of MIgG and environmental antigens in the
      medulla of bursal follicles exert positive effects on B-cell differentiation in
      the bursa in situ. 

PMID- 23974611
TI  - Differentiation of Boettcher's cells during postnatal development of rat cochlea.
AB  - Contrary to the highly specialized epithelial cells of the mammalian auditory
      organ, little is known about the surrounding cells and, in particular,
      Boettcher's cells (BC). Our morphological studies show that, in rats, these cells
      began their differentiation around postnatal day 8 (P8) reaching maturity around
      P20, when they are completely covered by Hensen's and Claudius' cells. Tight
      junctions were noted near the apex of BC, providing that they were in direct
      contact with the endolymphatic space, between approximately P8 and P16. We
      observed gap junctions between BC and adjacent cells before the end of the
      covering process suggesting the additional involvement of BC in potassium
      recycling into the endolymph. Adherens junctions were also seen between BC
      throughout their maturation. Importantly, we noticed cytoplasmic secretory
      granules and an accumulated material, probably a secretion, in the intercellular
      space, between P8 and P25. These results indicate that BC could basally take part
      in the secretion of the extracellular matrix of the basilar membrane. Finally, we
      show that the basolateral interdigitations of BC are longer and more tighlty
      grouped at maturity and harbour urea transporters as early as P18. Our
      observations thus support the view that BC perform several functions. 

PMID- 23974612
TI  - Insulins: historical and current perspectives.
AB  - Compounding pharmacists can participate in the management of diabetes by
      compounding preparations to treat health problems that are common among patients
      with the disease. These compounded preparations include topical preparations to
      relieve painful episodes of neuropathy, heal ulcers of the legs and feet, or
      relieve discomfort related to oral complications. Controlling blood glucose is of
      importance for the patient with diabetes. Therefore, compounding pharmacists need
      a concise knowledge of insulins and a ready resource for insulin facts and their
      associated rules for storing, mixing, and administration. Until technology
      reveals a means to actually correct the genetic machinery than cause diabetes,
      increasing his or her knowledge of insulin is one of the best ways a pharmacist
      can contribute to the care of patients with this disease. 

PMID- 23974613
TI  - Compounding for the Complications of Diabetes: Interviews with Compounding
      Pharmacists George B. Muller, RPh, and Jerrod Roberts, DPh.
AB  - Accounts of diabetes have been found in the earliest recorded medical treatises.
      Once thought to be a disease of the kidneys, diabetes pursued a relentlessly
      fatal course characterized by progressively worsening disability and excruciating
      discomfort. The discovery of insulin in the 1920s and the ongoing refinement of
      its use in treatment provided patients with diabetes with the hope of control
      (but not cure) of their disease. Those who benefit from a longer and much
      improved quality of life as a result of treatment with insulin, however,
      experience a constellation of chronic diabetes-related complications. In
      relieving the discomforts of those disorders, compounded preparations offer
      effective help. In this article, pharmacists George Muller and Jerrod Roberts
      discuss the topical compounds most effective in treating the painful neuropathy
      and cutaneous ulcers that many diabetic patients experience. Formulations for a
      variety of preparations for the complications of diabetes are also provided. 

PMID- 23974614
TI  - Certified diabetes educator: a credential for compounding pharmacists.
AB  - The common objectives of most medical professionals are to improve the medical
      condition of their patients, improve patients' understanding of their medical
      problem, reduce patients' concerns and stress related to their medical problem,
      and offer as many services as possible to make each patient's treatment safer and
      more effective, and their disease more manageable. A compounding pharmacist who
      has taken the necessary steps to become a Certified Diabetes Educator has the
      potential to become the primary diabetes educator in the community and an
      integral part of the healthcare team. The credentialing mechanism validates
      knowledge of specific medical problems and provides recognition of excellence in
      practice. Certification sets the industry standard. 

PMID- 23974615
TI  - Challenges of compounding for patients on the ketogenic diet.
AB  - A child on a ketogenic diet is a classic example of a patient who cannot take
      commercially available drug products. The ketogenic diet is a treatment option
      for young children who have catastrophic, intractable epilepsy or inborn
      metabolic defects involving glucose metabolism. Most children stay on the diet
      for 2 to 3 years and must be monitored by a team of healthcare professionals
      consisting of neurologists, nurses, dieticians, and pharmacists. The ketogenic
      diet is a high-fat, low-carbohydrate, and low-protein diet designed to increase
      the body's dependence on fatty acids for energy rather than glucose. The
      calculations of daily allowances of protein, fat, and carbohydrates must be
      exact. Compounding pharmacists assist the caregivers or patients and their
      dieticians by preparing medications whose carbohydrate content is calculated
      exactly. 

PMID- 23974616
TI  - Compounded treatments for erectile dysfunction: a common complication of
      diabetes.
AB  - Erectile dysfunction is a very common complication of diabetes; as many as 50% to
      80% of men with diabetes experience some degree of erectile dysfunction. Erectile
      dysfunction in men with diabetes mellitus usually is a result of the vascular and
      autonomic dysfunctions that often accompany uncontrolled hyperglycemia. A number
      of treatment options can be offered to a patient experiencing this complication.
      Compounding allows for specialized dosage forms of medications; with the help of
      an attentive physician and a compounding pharmacist, successful treatment of
      erectile dysfunction can become a reality.

PMID- 23974617
TI  - Including pets in diabetic care.
AB  - Pharmacists can play a valuable role in providing care and preparations for all
      species of patients with diabetes. Practical knowledge of the differences in
      diabetes between animals and humans is essential to providing diabetic care to
      multiple species. Pharmacists should familiarize themselves with the clinical
      signs of hyperglycemia and hypoglycemia in various species and be prepared to
      provide appropriate counseling, information, preparations, devices, and referral
      when signs of inadequate glycemic control arise. Pharmacists also should develop
      awareness of potential problems associated with the use of human diabetic
      preparations in animal patients. By maintaining a current knowledge of care for
      diabetic pets, including the significance of the patient's dietary habits,
      medical history, and genetics, and species-specific drug reactions, the
      compounding pharmacist can contribute, through collaboration with veterinarians
      and pet caregivers, to optimal patient outcomes when providing care for pets with
      diabetes. 

PMID- 23974618
TI  - Case report: shingles triple cream in the treatment of herpes zoster.

PMID- 23974619
TI  - Innovative Uses of Compounded Tranilast: An Interview with Compounding Pharmacist
      Larry J. Frieders, RPh.
AB  - Tranilast (Rizaben) is an antioxidant and an antiallergic antiangiogenesis, and
      anti-inflammatory agent that has been used to treat disorders ranging from
      bronchial asthma to keloids to oligozoospermia. In addition to its application in
      such therapeutically challenging conditions, tranilast in topical form provides
      relief from many relatively minor but compromising discomforts, such as hives or
      seasonal nasal congestion, that affect the quality of everyday life. Easily
      compounded and easy to apply, topical tranilast is a popular preparation sought
      in many compounding pharmacies. Larry J. Frieders, RPh, owner of The Compounder
      in Aurora, Illinois, describes his innovative use of tranilast and explains the
      value of that drug in the compounding armamentarium. The brief case reports of
      two staff members of The Compounder attest to the success of treatment with
      tranilast. 

PMID- 23974620
TI  - Records and record-keeping for the hospital compounding pharmacist.
AB  - The United States Pharmacopeial Convention, Inc., is recognized by federal law
      and by most state boards of pharmacy as the official group for setting the
      standards for pharmaceuticals and pharmacy practice, including compounding. The
      standards of United States Pharmacopeia Chapter 795 require that a pharmacy
      maintain records on a compounded preparation, including the formulation record,
      and a Material Safety Data Sheets file. The American Society of Health-Systems
      Pharmacists' guidelines require that hospital pharmacy departments maintain at
      least four sets of records in the compounding area: (1) compounding formulas and
      procedures, (2) compounding logs of all compounded preparations, including batch
      records and sample batch labels, (3) equipment maintenance records, and (4) a
      record of ingredients purchased, including cerificates of analysis and Material
      Saftey Data Sheets. Hospital compounding records may be inspected by any of
      several outside organizations, including state boards of pharmacy, third-party
      payers, the Joint Commission on Accreditaion of Healthcare Organizations, the
      Drug Enforcement Agency, and attorneys. With the existing standards and
      guidelines in place and the importance of documentation unquestionable, a record
      of pharmacy activites should be maintained in a compounding pharmacy so that
      preparations can be replicated consistently, the history of each ingredient
      traced, equipment maintenance and calibration verified, and compounding
      procedures evaluated easily. 

PMID- 23974621
TI  - Quality-control analytical methods: considerations in compounding peroral solid
      dosage forms.
AB  - Pharmacists who are engaged in drug compounding have specific guidelines and
      standards that are outlined in the United States Pharmacopeia-National Formulary.
      Of the many dosage forms that are available for the compounder, capsules and
      tablets (peroral solids) represent the most stable and convenient formulations
      for drug combinations. Dosage units must remain consistent, and the uniformity of
      dosage units should be demonstrable. Specific standards for the uniformity of
      dosage units are outlined in United States Pharmacopeia Chapter 905, which was
      developed specifically for the pharmaceutical industry. The uniformity of dosage
      units can be demonstrated by either of two methods, Content Uniformity or Weight
      Variation. Weighing and blending activities are critical in compounding.
      Therefore, all efforts should be expended to prevent errors in weighing and other
      steps that could adversely affect the final preparation. 

PMID- 23974622
TI  - Basics of compounding for hazardous drugs, part 4: developing the hazardous drugs
      list and containment.

PMID- 23974623
TI  - Stability of oseltamivir in various extemporaneous liquid preparations.
AB  - The purpose of this study was to determine the stability of oseltamivir, the
      active ingredient in Tamiflu, in contemporaneously compounded suspensions for a
      period of not less than 90 days. The suspension vehicles provided for the study
      were chosen because of ease of preparation, commercial availability, and
      palatability. Stability of the active ingredient was demonstrated for suspensions
      prepared in PCCA-Plus, PCCA Acacia, and 1% methylcellulose and was independent of
      storage temperature (tested temperatures were 2 deg C to 8 deg C and 25 deg C). A
      control sample of the commercial liquid form of Tamiflu was prepared, stored and
      analyzed along with the samples prepared from the contents of capsules. There was
      no difference in the apparent stability of the two forms of the drug preparation.

PMID- 23974624
TI  - Evaluating combinational illumination estimation methods on real-world images.
AB  - Illumination estimation is an important component of color constancy and
      automatic white balancing. A number of methods of combining illumination
      estimates obtained from multiple subordinate illumination estimation methods now
      appear in the literature. These combinational methods aim to provide better
      illumination estimates by fusing the information embedded in the subordinate
      solutions. The existing combinational methods are surveyed and analyzed here with
      the goals of determining: 1) the effectiveness of fusing illumination estimates
      from multiple subordinate methods; 2) the best method of combination; 3) the
      underlying factors that affect the performance of a combinational method; and 4)
      the effectiveness of combination for illumination estimation in multiple
      illuminant scenes. The various combinational methods are categorized in terms of
      whether or not they require supervised training and whether or not they rely on
      high-level scene content cues (e.g., indoor versus outdoor). Extensive tests and
      enhanced analyzes using three data sets of real-world images are conducted. For
      consistency in testing, the images were labeled according to their high-level
      features (3D stages, indoor/outdoor) and this label data is made available on
      line. The tests reveal that the trained combinational methods (direct combination
      by support vector regression in particular) clearly outperform both the non
      combinational methods and those combinational methods based on scene content
      cues. 

PMID- 23974625
TI  - Lattice structure for generalized-support multidimensional linear phase perfect
      reconstruction filter bank.
AB  - Multidimensional linear phase perfect reconstruction filter bank (MDLPPRFB) can
      be designed and implemented via lattice structure. The lattice structure for the
      MDLPPRFB with filter support N(MXi) has been published by Muramatsu , where M is
      the decimation matrix, Xi is a positive integer diagonal matrix, and N(N) denotes
      the set of integer vectors in the fundamental parallelepiped of the matrix N.
      Obviously, if Xi is chosen to be other positive diagonal matrices instead of only
      positive integer ones, the corresponding lattice structure would provide more
      choices of filter banks, offering better trade-off between filter support and
      filter performance. We call such resulted filter bank as generalized-support
      MDLPPRFB (GSMDLPPRFB). The lattice structure for GSMDLPPRFB, however, cannot be
      designed by simply generalizing the process that Muramatsu employed. Furthermore,
      the related theories to assist the design also become different from those used
      by Muramatsu . Such issues will be addressed in this paper. To guide the design
      of GSMDLPPRFB, the necessary and sufficient conditions are established for a
      generalized-support multidimensional filter bank to be linear-phase. To determine
      the cases we can find a GSMDLPPRFB, the necessary conditions about the existence
      of it are proposed to be related with filter support and symmetry polarity (i.e.,
      the number of symmetric filters ns and antisymmetric filters na). Based on a
      process (different from the one Muramatsu used) that combines several polyphase
      matrices to construct the starting block, one of the core building blocks of
      lattice structure, the lattice structure for GSMDLPPRFB is developed and shown to
      be minimal. Additionally, the result in this paper includes Muramatsu's as a
      special case. 

PMID- 23974626
TI  - Landmark image super-resolution by retrieving web images.
AB  - This paper proposes a new super-resolution (SR) scheme for landmark images by
      retrieving correlated web images. Using correlated web images significantly
      improves the exemplar-based SR. Given a low-resolution (LR) image, we extract
      local descriptors from its up-sampled version and bundle the descriptors
      according to their spatial relationship to retrieve correlated high-resolution
      (HR) images from the web. Though similar in content, the retrieved images are
      usually taken with different illumination, focal lengths, and shot perspectives,
      resulting in uncertainty for the HR detail approximation. To solve this problem,
      we first propose aligning these images to the up-sampled LR image through a
      global registration, which identifies the corresponding regions in these images
      and reduces the mismatching. Second, we propose a structure-aware matching
      criterion and adaptive block sizes to improve the mapping accuracy between LR and
      HR patches. Finally, these matched HR patches are blended together by solving an
      energy minimization problem to recover the desired HR image. Experimental results
      demonstrate that our SR scheme achieves significant improvement compared with
      four state-of-the-art schemes in terms of both subjective and objective
      qualities. 

PMID- 23974627
TI  - Estimating spatially varying defocus blur from a single image.
AB  - Estimating the amount of blur in a given image is important for computer vision
      applications. More specifically, the spatially varying defocus point-spread
      functions (PSFs) over an image reveal geometric information of the scene, and
      their estimate can also be used to recover an all-in-focus image. A PSF for a
      defocus blur can be specified by a single parameter indicating its scale. Most
      existing algorithms can only select an optimal blur from a finite set of
      candidate PSFs for each pixel. Some of those methods require a coded aperture
      filter inserted in the camera. In this paper, we present an algorithm estimating
      a defocus scale map from a single image, which is applicable to conventional
      cameras. This method is capable of measuring the probability of local defocus
      scale in the continuous domain. It also takes smoothness and color edge
      information into consideration to generate a coherent blur map indicating the
      amount of blur at each pixel. Simulated and real data experiments illustrate
      excellent performance and its successful applications in foreground/background
      segmentation. 

PMID- 23974628
TI  - Comments on "SVD-based modeling for image texture classification using wavelet
      transform".
AB  - This correspondence points out that in [1] there are some errors in two important
      formulas and the performance of the proposed singular value decomposition (SVD)
      feature is severely overestimated. It also presents a modified SVD feature which
      competes with the Gabor feature.

PMID- 23974629
TI  - FADD the bad in head and neck cancer.
AB  - It has been known for many years that the protein Fas-associated death domain
      (FADD) is an essential protein forming the apical portion of the extrinsic
      apoptosis pathway that permits association of death receptors, e.g., CD95, DR4,
      DR5 with pro-caspases 8 and 10, thereby facilitating caspase activation (e.g.,
      ref. 1, and references therein). It is also known that FADD can recruit other
      proteins to regulate NFkappaB and MAPK pathways which in turn can promote
      proliferation and cell cycle progression. In NSCLC high expression of FADD has
      been associated with shorter survival times and lymph node metastasis or oral
      cancer and worse survival, and the present manuscript in head and neck cancer
      demonstrates similar findings with respect to lymph node metastasis and
      survival.(2,3)

PMID- 23974630
TI  - Bench test assessment of mainstream capnography during high frequency oscillatory
      ventilation.
AB  - To assess the feasibility, stability and predictability of pCO2 measurement
      (PETCO2) using a main stream capnograph in a high frequency oscillatory
      ventilation circuit. A commercially available capnograph was mounted into a high
      frequency oscillatory ventilator patient circuit, adjustable CO2 flow was
      introduced into an artificial lung and the output of the CO2 sensor assessed
      under varying ventilator settings. Influence of oxygen content, pressures, heat
      and moisture were recorded. A linear relationship between CO2 flow rate and
      PETCO2 was found. Varying ventilator settings influenced the measurements, but
      the results for PETCO2 remained within a range of 1.5 mmHg above or under then
      mean measurement value. Measurements remained stable despite humidification,
      heat, pressure amplitudes or mean airway pressure changes. From this bench test,
      we conclude it is feasible to measure PETCO2 using a main stream capnograph
      during high frequency oscillatory conditions, these measurements were stable
      during the experiment. Changes in CO2 production or output can be detected. The
      system may prove to be of clinical value, but further in vivo measurements are
      warranted.

PMID- 23974631
TI  - Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus.
AB  - Even though highly active anti-retroviral therapy is able to keep HIV-1
      replication under control, the virus can lie in a dormant state within the host
      genome, known as a latent reservoir, and poses a threat to re-emerge at any time.
      However, novel technologies aimed at disrupting HIV-1 provirus may be capable of
      eradicating viral genomes from infected individuals. In this study, we showed the
      potential of the CRISPR/Cas9 system to edit the HIV-1 genome and block its
      expression. When LTR-targeting CRISPR/Cas9 components were transfected into HIV-1
      LTR expression-dormant and -inducible T cells, a significant loss of LTR-driven
      expression was observed after stimulation. Sequence analysis confirmed that this
      CRISPR/Cas9 system efficiently cleaved and mutated LTR target sites. More
      importantly, this system was also able to remove internal viral genes from the
      host cell chromosome. Our results suggest that the CRISPR/Cas9 system may be a
      useful tool for curing HIV-1 infection. 

PMID- 23974632
TI  - Arthroscopic treatment for posterior tibial tendon lesions with a posterior
      approach.
AB  - PURPOSE: To evaluate clinical results of arthroscopic treatment for posterior
      tibial tendon (PTT) lesions using a posterior approach. METHODS: Sixteen patients
      with PTT lesions underwent arthroscopic treatment using a posterior approach.
      After routine posterior arthroscopy to expose the posterior tibiotalar
      compartment, the posterior subtalar compartment, and the flexor hallucis longus
      tendon, the shaver was then moved through the flexor hallucis longus tendon to
      detect and treat the PTT lesion, including synovectomy, debridement, and repair
      of the PTT. American Orthopaedic Foot and Ankle Society Ankle-Hindfoot (AOFAS)
      scale and visual analog scale (VAS) for subjective satisfaction were used to
      evaluate pre- and post-operative clinical results. RESULTS: Fifteen patients (94
      %) (15 ankles) were followed for a mean of 26 +/- 10 months. No patients
      experienced vascular or nerve complications during or after the operation. Mean
      AOFAS score improved from 49 +/- 12 points preoperatively to 84 +/- 8.5 points
      post-operatively (p = 0.000). Mean VAS improved from 6.2 +/- 1.7 preoperatively
      to 2.4 +/- 1.3 post-operatively (p = 0.000). There were three patients (20 %)
      with excellent outcomes, eight patients (53 %) with good outcomes, three patients
      (20 %) with fair outcomes, and one patient (7 %) with a poor outcome at follow
      up. CONCLUSIONS: A posterior arthroscopic approach can provide a safe, reliable
      technique for detecting and treating PTT lesions and a satisfactory surgical
      outcome. The technique is an alternative to PTT tendoscopy.

PMID- 23974634
TI  - A strained organic field-effect transistor with a gate-tunable superconducting
      channel.
AB  - In state-of-the-art silicon devices, mobility of the carrier is enhanced by the
      lattice strain from the back substrate. Such an extra control of device
      performance is significant in realizing high-performance computing and should be
      valid for electric-field-induced superconducting (SC) devices, too. However, so
      far, the carrier density is the sole parameter for field-induced SC interfaces.
      Here we show an active organic SC field-effect transistor whose lattice is
      modulated by the strain from the substrate. The soft organic lattice allows
      tuning of the strain by a choice of the back substrate to make an induced SC
      state accessible at low temperature with a paraelectric solid gate. An active
      three-terminal Josephson junction device thus realized is useful both in advanced
      computing and in elucidating a direct connection between filling-controlled and
      bandwidth-controlled SC phases in correlated materials. 

PMID- 23974633
TI  - Iliotibial band autograft versus bone-patella-tendon-bone autograft, a possible
      alternative for ACL reconstruction: a 15-year prospective randomized controlled
      trial.
AB  - PURPOSE: The long-term results after using the iliotibial band autograft (ITB) in
      anterior cruciate ligament (ACL) reconstruction are not fully known. If equal in
      quality to conventional methods, the ITB graft could be a useful alternative as a
      primary graft, in revision surgery or multi-ligament reconstruction. The purpose
      is to assess whether the ITB autograft is a long-term reliable alternative to the
      bone-patella-tendon-bone (BPTB) autograft, using a prospective randomized
      controlled trial design. METHODS: From 1995 to 1996, sixty patients scheduled for
      primary ACL reconstruction were included in a prospective randomized controlled
      trial. Three senior knee surgeons, experienced in both types of ACL surgery,
      performed all the operations. A standardized and supervised rehabilitation
      programme was used for both groups for 6 months. Thirty patients received the ITB
      reconstruction, and 30 received the BPTB reconstruction. Forty-nine participated
      at follow-up in 2010 (82%). Primary outcome was the failure rate after ACL
      reconstruction. Secondary outcomes were knee injury osteoarthritis outcome score
      (KOOS) [pain, symptoms, Sport/Rec, quality of life (QOL), daily living function],
      Tegner activity scale, anterior knee pain-score, Lysholm score, Rolimeter laxity,
      extension deficit, single hop and crossover hop for distance. RESULTS: At 15-year
      follow-up, no significant difference existed between the groups. Graft failure
      occurred in 4 ITB subjects (16%) and 3 BPTB subjects (13%). KOOS (Sport/Rec) for
      the ITB group was 75 and 73 for the BPTB group. The KOOS (QOL) was 72 and 68 for
      the ITB group and BPTB group, respectively. CONCLUSION: Similar graft failure
      rates and KOOS were found when comparing ITB- and BPTB-operated individuals, at
      15-year follow-up. The ITB graft had equal long-term clinical results compared to
      the BPTB graft and is recommended as a reliable alternative autograft for ACL
      reconstruction. LEVEL OF EVIDENCE: Therapeutic studies, Level I.

PMID- 23974636
TI  - Communication in difficult situations: what would a friend say?

PMID- 23974638
TI  - Cytisine, the world's oldest smoking cessation aid.

PMID- 23974637
TI  - Populations at risk for severe or complicated influenza illness: systematic
      review and meta-analysis.
AB  - OBJECTIVE: To evaluate risk factors for severe outcomes in patients with seasonal
      and pandemic influenza. DESIGN: Systematic review. STUDY SELECTION: Observational
      studies reporting on risk factor-outcome combinations of interest in participants
      with influenza. Outcomes included death, ventilator support, admission to
      hospital, admission to an intensive care unit, pneumonia, and composite outcomes.
      DATA SOURCES: Medline, Embase, CINAHL, Global Health, and the Cochrane Central
      Register of Controlled Trials to March 2011. RISK OF BIAS ASSESSMENT: Newcastle
      Ottawa scale to assess the risk of bias. GRADE framework to evaluate the quality
      of evidence. RESULTS: 63 537 articles were identified of which 234 with a total
      of 610 782 participants met the inclusion criteria. The evidence supporting risk
      factors for severe outcomes of influenza ranged from being limited to absent.
      This was particularly relevant for the relative lack of data for non-2009 H1N1
      pandemics and for seasonal influenza studies. Limitations in the published
      literature included lack of power and lack of adjustment for confounders was
      widespread: adjusted risk estimates were provided for only 5% of risk factor
      outcome comparisons in 39 of 260 (15%) studies. The level of evidence was low for
      "any risk factor" (odds ratio for mortality 2.77, 95% confidence interval 1.90 to
      4.05 for pandemic influenza and 2.04, 1.74 to 2.39 for seasonal influenza),
      obesity (2.74, 1.56 to 4.80 and 30.1, 1.74 to 2.39), cardiovascular diseases
      (2.92, 1.76 to 4.86 and 1.97, 1.06 to 3.67), and neuromuscular disease (2.68,
      1.91 to 3.75 and 3.21, 1.84 to 5.58). The level of evidence was very low for all
      other risk factors. Some well accepted risk factors such as pregnancy and
      belonging to an ethnic minority group could not be identified as risk factors. In
      contrast, women who were less than four weeks post partum had a significantly
      increased risk of death from pandemic influenza (4.43, 1.24 to 15.81).
      CONCLUSION: The level of evidence to support risk factors for influenza related
      complications is low and some well accepted risk factors, including pregnancy and
      ethnicity, could not be confirmed as risks. Rigorous and adequately powered
      studies are needed.

PMID- 23974639
TI  - Recent high death rates in older people are not exceptional, says Public Health
      England.

PMID- 23974640
TI  - Smoke screen: Indian film and television's anti-tobacco obsession.

PMID- 23974641
TI  - Senior Dutch researcher sacked for manipulating data in rheumatoid arthritis drug
      trial.

PMID- 23974643
TI  - Amyotrophic lateral sclerosis: new hope for an old disease?

PMID- 23974642
TI  - Long-term effects of tafamidis for the treatment of transthyretin familial
      amyloid polyneuropathy.
AB  - Tafamidis, a transthyretin (TTR) kinetic stabilizer, delayed neuropathic
      progression in patients with Val30Met TTR familial amyloid polyneuropathy (TTR
      FAP) in an 18-month randomized controlled trial (study Fx-005). This 12-month,
      open-label extension study evaluated the long-term safety, tolerability, and
      efficacy of tafamidis 20 mg once daily in 86 patients who earlier received
      blinded treatment with tafamidis or placebo. Efficacy measures included the
      Neuropathy Impairment Score in the Lower Limbs (NIS-LL), Norfolk Quality of Life
      Diabetic Neuropathy total quality of life (TQOL) score, and changes in neurologic
      function and nutritional status. We quantified the monthly rates of change in
      efficacy measures, and TTR stabilization, and monitored adverse events (AEs).
      Patients who continued on tafamidis had stable rates of change in NIS-LL (from
      0.08 to 0.11/month; p = 0.60) and TQOL (from -0.03 to 0.25; p = 0.16). In
      patients switched from placebo, the monthly rate of change in NIS-LL declined
      (from 0.34 to 0.16/month; p = 0.01), as did TQOL score (from 0.61 to -0.16; p <
      0.001). Patients treated with tafamidis for 30 months had 55.9 % greater
      preservation of neurologic function as measured by the NIS-LL than patients in
      whom tafamidis was initiated later. Plasma TTR was stabilized in 94.1 % of
      patients treated with tafamidis for 30 months. AEs were similar between groups;
      no patients discontinued because of an AE. Long-term tafamidis was well
      tolerated, with the reduced rate of neurologic deterioration sustained over 30
      months. Tafamidis also slowed neurologic impairment in patients previously given
      placebo, but treatment benefits were greater when tafamidis was begun earlier.

PMID- 23974644
TI  - Verbal dysflucency as a consequence of basal ganglia infarction with selective
      involvement of dorsolateral prefrontal fiber tract.

PMID- 23974645
TI  - Symptomatic cavernous malformations of the brainstem: functional outcome after
      microsurgical resection.
AB  - Brainstem cavernous malformations are associated with a considerable risk of
      hemorrhage and subsequent morbidity. This study provides a detailed work-up of
      clinical and radiological outcome as well as identification of prognostic factors
      in patients who had suffered from symptomatic hemorrhages. Patients who had
      undergone surgery of symptomatic BSCMs were evaluated pre- and postoperatively
      both neurologically and neuroradiologically supplemented by telephone interviews.
      Additionally, patients were scored according to the Scandinavian Stroke Scale.
      Multiple uni- and multivariate analyses of possible clinical and radiological
      prognostic factors were conducted. The study population comprised 35 patients.
      Mean age at operation was 39.3 +/- 13.0 years with microsurgical resection of a
      total of 37 different BSCMs between 2002 and 2011. Median clinical follow-up was
      44.0 months (range 8-116 months). Postoperative MRI showed eventually complete
      resection of all BSCMs. Postoperative overall outcome revealed complete
      resolution of neurological symptoms for 5/35 patients, 14/35 improved and 9/35
      remained unchanged. 7/35 suffered from a postoperative new and permanent
      neurological deficit, mostly affecting the facial nerve or hemipareses with mild
      impairment. Pre- and postoperative Scandinavian Stroke Scale scores were 11.0 +/-
      2.4 and 11.4 +/- 2.2 (p = 0.55). None of the analyzed factors were found to
      significantly correlate with patients' clinical outcome. Complete resection of
      brainstem cavernous malformations can be achieved with an acceptable risk for
      long-term morbidity and surgery-related new deficits (~20 %). Neurological
      outcome is mainly determined within the first 6 months after surgery. Surgical
      treatment of brainstem cavernous malformations is recommended in symptomatic
      patients, in whom the lesion is accessible for surgery. 

PMID- 23974646
TI  - Robert Bartholow (1831-1904).

PMID- 23974647
TI  - Diffusion tensor imaging and correlations to Parkinson rating scales.
AB  - The contribution of various brain areas to the overall progression of Parkinson's
      disease remains to be determined. In this study, we apply MRI diffusion tensor
      imaging to investigate how alterations in diffusion relate to phenotype and
      symptoms measured by clinical rating scales. Sixty-four patients were
      investigated at baseline and three follow-ups (1, 3 and 5 years). Thirty-six
      patients remained in the last follow-up. Regions of interests included frontal
      white matter, basal ganglia, thalamus, and cerebellum. Scoring on the Unified
      Parkinson's Disease Rating Scale (UPDRS) I, II, III, Hoehn and Yahr (HY) scale
      and the Schwab and England scale (SE) was determined. Mean, radial, and axial
      diffusion and fractional anisotropy were modeled with phenotype and clinical
      scales in a multivariate/univariate analysis correcting for other covariates.
      Significance was set at 0.05 Bonferroni corrected. All rating scales except UPDRS
      III significantly correlated to the diffusion measures, as did clinical
      phenotype. Specifically, putamen, globus pallidus, and thalamus demonstrated
      higher diffusion with worsening scores. Diffusion in thalamus was higher in the
      tremor dominant phenotype than in postural imbalance and gait disturbance.
      Decline in overall functionality (UPDRS II and SE scale), including mental status
      (UPDRS I) and stage of the disease (HY scale), in Parkinson's disease is related
      to altered diffusion in the lentiform nucleus and thalamus. Motor function is not
      mirrored in diffusion changes, possibly due to medication. Tremor dominant PD
      patients show diffusion alterations in the thalamus, but the significance of this
      for tremor generation remains to be determined. 

PMID- 23974648
TI  - [Atrial fibrillation in the ICU. Distinct entity--special treatment?].
AB  - Atrial fibrillation (AF) is the single most frequent arrhythmia in the intensive
      care unit, occurring among 44-61 % of all patients with arrhythmias in the
      intensive care unit. The success rate of electrical cardioversion (DC-CV) early
      after surgery is as low as 10-35 % in postoperative AF but 6 weeks after
      discharge 90 % are in sinus rhythm (SR). Several guidelines recommend rate
      control in these patients and rate control with beta-blockers and calcium channel
      blockers is not inferior with respect to outcome, 6 min walk test, and quality of
      life. DC-CV is recommended in unstable and heart failure patients. The term
      resistant AF is suggested for that distinct situation of AF not amenable to
      cardioversion solely in the acute phase of critical illness. 

PMID- 23974649
TI  - [Not all drugs are the same].
AB  - Drug use has changed dramatically in recent years. Classic drugs such as
      marijuana, heroin, and cocaine are being pushed progressively into the
      background. Consumer behavior has also changed and so-called designer drugs
      dominate the market. Designer drugs are synthetic or semi-synthetic drugs based
      on a well-known substance. Mostly amphetamine derivates, synthetic cannabinoids,
      and synthetic cathinone are used. Legal monitoring capabilities are limited,
      since these substances are so-called legal highs and are commercially available.
      A ban often follows a latency period. Estimating the risk is difficult, and the
      problem of intoxication increases. This overview presents the activity profiles
      and risks of classic and new drugs. 

PMID- 23974650
TI  - Synergy between the pharmacological chaperone 1-deoxygalactonojirimycin and
      agalsidase alpha in cultured fibroblasts from patients with Fabry disease.

PMID- 23974651
TI  - Noncompaction of the ventricular myocardium and hydrops fetalis in cobalamin C
      disease: Response to letter "Disappearance of congenital noncompaction in
      hereditary cobalamin-C-deficiency 2.5 years after birth" by J. Finsterer and
      Claudia Stollberger, DOI 10.1007/s10545-013-9612-4.

PMID- 23974652
TI  - Oral manifestations of 17 patients affected with mucopolysaccharidosis type VI.
AB  - OBJECTIVE: To assess oral manifestations of 17 patients with
      mucopolysaccharidosis type VI (MPS VI) or Maroteaux-Lamy syndrome. METHODS: We
      performed comprehensive oral examinations in 17 patients with MPS VI. Panoramic
      radiographs was performed only in 14 patients. All patients were of Thai,
      Turkish, and Indian origins. Ten of 17 patients had enzyme replacement therapy
      (ERT) (Naglazyme). Most Turkish patients (10/11) were on ERT. The Thai and Indian
      patients have never had ERT. RESULTS: Oral and radiographic examinations showed
      that hypoplastic mandibular condyles (93.3 %), malposition of unerupted teeth
      (92.9 %), large dental follicles (92.3 %), anterior open bite (86.7 %), maxillary
      constriction (56.3 %), and taurodontism (53.8 %) were common among patients with
      MPS VI. Newly recognized oral findings found in our study included taurodontism,
      long tooth roots, abnormal frenum, missing teeth, supernumerary teeth, and
      microdontia. Two patients who started ERT prior to 3 years old did not develope
      anterior open bite and one of them had mildly affected mandibular condyles.
      CONCLUSION: Our study provides the most comprehensive study of oral
      manifestations in patients with MPS VI. Receiving ERT at very young ages may
      lessen craniofacial malformations including hypoplasic mandibular condyles and
      anterior open bite. Oral manifestations can be used as diagnostic features for
      MPS VI prior to assessing leukocyte ARSB activity or urinary excretion of
      dermatan sulfate.

PMID- 23974654
TI  - The Iranian version of the Premenstrual Symptoms Screening Tool (PSST): a
      validation study.
AB  - The objective of the current study was to translate and test psychometric
      properties of the Premenstrual Symptoms Screening Tool (PSST) in Iran. Using a
      standard "forward-backward" procedure, the English version of PSST was translated
      into Persian. A random sample of university students aged 18 years and over
      completed the questionnaire in Tehran, Iran. Psychometric properties of the
      Iranian version of PSST were assessed by performing reliability (internal
      consistency) and validity analyses [Content Validity Ratio (CVR) and Content
      Validity Index (CVI)]. In all, 925 female students took part in the study. Of
      these, 284 (30.7 %) had premenstrual syndrome (PMS) and 119 (12.9 %) had
      premenstrual dysphoric disorder (PMDD). Reliability of the PSST as measured by
      internal consistency was found to be satisfactory (Cronbach's alpha coefficient,
      0.93). The content validity as assessed by CVR and CVI were desirable (0.7 and
      0.8, respectively). The Iranian version of PSST seems to be a reliable and valid
      measure of detecting PMS and PMDD in Iranian young female populations. 

PMID- 23974653
TI  - Reduced response of Cystathionine Beta-Synthase (CBS) to S-Adenosylmethionine
      (SAM): Identification and functional analysis of CBS gene mutations in
      Homocystinuria patients.
AB  - A reduced response of cystathionine beta-synthase (CBS) to its allosteric
      activator S-adenosylmethionine (SAM) has been reported to be a cause of CBS
      dysfunction in homocystinuria patients. In this work we performed a retrospective
      analysis of fibroblast data from 62 homocystinuria patients and found that 13 of
      them presented a disturbed SAM activation. Their genotypic background was
      identified and the corresponding CBS mutant proteins were produced in E. coli.
      Nine distinct mutations were detected in 22 independent alleles: the novel
      mutations p.K269del, p.P427L, p.S500L and p.L540Q; and the previously described
      mutations p.P49L, p.C165Rfs*2, p.I278T, p.R336H and p.D444N. Expression levels
      and residual enzyme activities, determined in the soluble fraction of E. coli
      lysates, strongly correlated with the localization of the affected amino acid
      residue. C-terminal mutations lead to activities in the range of the wild-type
      CBS and to oligomeric forms migrating faster than tetramers, suggesting an
      abnormal conformation that might be responsible for the lack of SAM activation.
      Mutations in the catalytic core were associated with low protein expression
      levels, decreased enzyme activities and a higher content of high molecular mass
      forms. Furthermore, the absence of SAM activation found in the patients'
      fibroblasts was confirmed for all but one of the characterized recombinant
      proteins (p.P49L). Our study experimentally supports a deficient regulation of
      CBS by SAM as a frequently found mechanism in CBS deficiency, which should be
      considered not only as a valuable diagnostic tool but also as a potential target
      for the development of new therapeutic approaches in classical homocystinuria. 

PMID- 23974655
TI  - Neurocognitive deficits following primary brain tumor treatment: systematic
      review of a decade of comparative studies.
AB  - There has been an increase in the prevalence of adults diagnosed with and treated
      for primary brain tumors. Cognitive deficits are a common long-term effect in
      brain tumor survivors. The objective of this paper is to examine whether these
      deficits are specific to those diagnosed with and treated for a primary brain
      tumor. A systematic review of the medical literature from 2002 to 2012 was
      conducted to investigate neurocognitive deficits in brain tumor survivors (post
      primary treatment) compared to healthy controls. Four studies were identified
      that met all inclusion criteria. Gliomas were the most common form of tumor
      included. Neuropsychological evaluation identified cognitive deficits in brain
      tumor survivors on tests of working memory, cognitive control and flexibility,
      cognitive processing speed, visual searching, planning and foresight, and general
      attention. While age, education, and gender can influence cognitive function, the
      present review indicates that deficits exist beyond those accounted for by these
      factors. Many primary brain tumor survivors are involved in roles (e.g.,
      employee, parent, spouse/partner, student) that require optimal performance of
      these cognitive skills. Future research should evaluate brain tumor survivors on
      functional challenges resulting from these cognitive sequelae and develop
      effective ways to mitigate them. 

PMID- 23974657
TI  - Drug-domain interaction networks in myocardial infarction.
AB  - It has been well recognized that the pace of the development of new drugs and
      therapeutic interventions lags far behind biological knowledge discovery. Network
      based approaches have emerged as a promising alternative to accelerate the
      discovery of new safe and effective drugs. Based on the integration of several
      biological resources including two recently published datasets i.e., Drug-target
      interactions in myocardial infarction (My-DTome) and drug-domain interaction
      network, this paper reports the association between drugs and protein domains in
      the context of myocardial infarction (MI). A MI drug-domain interaction network,
      My-DDome, was firstly constructed, followed by topological analysis and
      functional characterization of the network. The results show that My-DDome has a
      very clear modular structure, where drugs interacting with the same domain(s)
      within each module tend to have similar therapeutic effects. Moreover it has been
      found that drugs acting on blood and blood forming organs (ATC code B) and
      sensory organs (ATC code S) are significantly enriched in My-DDome (p <
      0.000001), indicating that by incorporating protein domain information into My
      DTome, more detailed insights into the interplay between drugs, their known
      targets, and seemingly unrelated proteins can be revealed.

PMID- 23974656
TI  - Recurrent high-grade glioma treated with bevacizumab: prognostic value of MGMT
      methylation, EGFR status and pretreatment MRI in determining response and
      survival.
AB  - Although bevacizumab represented an important advance in treatment of recurrent
      high-grade gliomas (HGG), responses occur in fewer than half of patients. There
      are no validated biomarkers for anti-angiogenic therapy that are available for
      routine clinical use. We assessed the prognostic values of imaging and molecular
      markers in this patient population. MRI scans from 191 patients with recurrent
      HGG obtained prior to initiating bevacizumab were reviewed for areas of
      enhancement, necrosis, T2/FLAIR abnormality, and ADC values. Serial MRI scans
      following the initiation of bevacizumab were evaluated for response and
      progression. Non-radiographic markers including EGFR and MGMT status were also
      assessed with respect to response and patient survival. 65 of 191 patients (34 %)
      showed complete or partial response at the time of their best response MRI and
      demonstrated longer progression free survival (PFS) and overall survival (OS)
      compared to the group without response (PFS: 6.9 vs 3.5 months, OS: 10.9 vs 6.1
      months). Minimum ADC values within enhancing and non-enhancing regions were lower
      in responders compared to those of non-responders (1,099 vs 984 * 10(-6) mm(2)/s,
      p = 0.006). Smaller enhancing area was associated with longer OS (HR = 1.99, p =
      0.017). The ratio of T2/FLAIR to enhancing area was prognostic of OS for only the
      Grade III HGG subgroup (HR = 0.14, p = 0.004). Area of enhancing tumor at
      baseline can stratify survival in patients with recurrent HGG treated with
      bevacizumab. The extent of edema relative to enhancing area may have a prognostic
      role specific to Grade III HGG.

PMID- 23974658
TI  - PPIExtractor: a protein interaction extraction and visualization system for
      biomedical literature.
AB  - Protein-protein interactions (PPIs) play a key role in various aspects of the
      structural and functional organization of the cell. Knowledge about them unveils
      the molecular mechanisms of biological processes. However, the amount of
      biomedical literature regarding protein interactions is increasing rapidly and it
      is difficult for interaction database curators to detect and curate protein
      interaction information manually. In this paper, we present a PPI extraction
      system, termed PPIExtractor, which automatically extracts PPIs from biomedical
      text and visualizes them. Given a Medline record dataset, PPIExtractor first
      applies Feature Coupling Generalization (FCG) to tag protein names in text, next
      uses the extended semantic similarity-based method to normalize them, then
      combines feature-based, convolution tree and graph kernels to extract PPIs, and
      finally visualizes the PPI network. Experimental evaluations show that
      PPIExtractor can achieve state-of-the-art performance on a DIP subset with
      respect to comparable evaluations.

PMID- 23974659
TI  - Identifying protein complexes based on multiple topological structures in PPI
      networks.
AB  - Various computational algorithms are developed to identify protein complexes
      based on only one of specific topological structures in protein-protein
      interaction (PPI) networks, such as cliques, dense subgraphs, core-attachment
      structures and starlike structures. However, protein complexes exhibit intricate
      connections in a PPI network. They cannot be fully detected by only single
      topological structure. In this paper, we propose an algorithm based on multiple
      topological structures to identify protein complexes from PPI networks. In the
      proposed algorithm, four single topological structure based algorithms are first
      employed to identify raw predictions with specific topological structures,
      respectively. Those raw predictions are trimmed according to their topological
      information or GO annotations. Similar results are carefully merged before
      generating final predictions. Numerical experiments are conducted on a yeast PPI
      network of DIP and a human PPI network of HPRD. The predicted results show that
      the multiple topological structure based algorithm can not only obtain a more
      number of predictions, but also generate results with high accuracy in terms of f
      score, matching with known protein complexes and functional enrichments with GO.

PMID- 23974660
TI  - Intestinal flow of a couple stress nanofluid in arteries.
AB  - The current article discusses the influence of nanofluid on the peristaltic flow
      of an incompressible couple stress fluid in a two-dimensional uniform tube. The
      problem formulation is accessible in an upsurge structure of orientation for
      equations of momentum, energy, and concentrations. The continuity, linear
      momentum, energy, and nanoparticle equations lead to the mathematical
      development. HPM is used to get the solutions for velocity, temperature,
      nanoparticle, and pressure gradient. The solutions contain the Brownian motion
      number N(b), thermophoresis number N(t), local temperature Grashof number B(r),
      and local nanoparticle Grashof number G(r). The physical features of different
      embedded parameters are analyzed and discussed physically in detail.

PMID- 23974661
TI  - Normal forms for some classes of sequential spiking neural P systems.
AB  - Spiking neural P systems (SN P systems, for short) are a class of distributed
      parallel computing devices inspired from the way neurons communicate by means of
      spikes, where each neuron can have several spiking rules and forgetting rules and
      neurons work in parallel in the sense that each neuron that can fire should fire
      at each computation step. In this work, we consider SN P systems with the
      restrictions: 1) systems are simple (resp. almost simple) in the sense that each
      neuron has only one rule (resp. except for one neuron); 2) at each step the
      neuron(s) with the maximum number of spikes among the neurons that can spike will
      fire. These restrictions correspond to that the systems are simple or almost
      simple and a global view of the whole network makes the systems sequential. The
      computation power of simple SN P systems and almost simple SN P systems working
      in the sequential mode induced by maximum spike number is investigated.
      Specifically, we prove that such systems are Turing universal as both number
      generating and accepting devices. The results improve the corresponding ones in
      Theor. Comput. Sci., 410 (2009), 2982-2991. 

PMID- 23974662
TI  - Can chronic visual discomfort measures accurately predict acute symptoms?
AB  - PURPOSE: Several surveys exist to determine the severity and frequency of chronic
      symptoms related to visual discomfort. To our knowledge, there are no studies
      that investigate the potential of chronic visual discomfort ratings to predict
      acute discomfort symptoms that are experienced after tests of accommodation and
      vergence. We examined the ability of two measures of chronic visual discomfort
      symptoms to predict acute symptoms experienced. METHODS: The Conlon et al. and
      the convergence insufficiency symptom surveys were administered to 40
      participants to assess chronic visual discomfort symptoms. Two measures were used
      to assess acute symptoms. The first consisted of four Likert-scaled questions
      relating to comfort level during last test, visual distortions or movement,
      discomfort caused by overhead lights, and presence of headache symptoms. These
      questions were asked before and after binocular examination, and the scores were
      used to generate a postexamination symptom score. The second measure of acute
      symptoms consisted of participants rating their general discomfort on a four
      point Likert scale after each binocular test, and the ratings were summed to
      produce a General Symptom Score. Participants were then categorized into a high
      or low Post-exam symptom group and General symptom group. Data were analyzed with
      a binary logistic regression to determine whether the chronic surveys could
      predict acute symptom group classification. RESULTS: Approximately 75% of
      predictions were accurate for either chronic symptom survey. Headache, soreness,
      and eye-related questions were more reliable predictors of symptom acute outcome.
      CONCLUSIONS: These data suggest that the Conlon and Convergence Insufficiency
      Symptom Survey (CISS) surveys are good predictors of acute symptoms induced
      during a binocular examination and validate the use of chronic symptom surveys as
      screening tools for symptomatic binocular dysfunction. Further investigation is
      required to determine predictability of accommodative or vergence performance.

PMID- 23974663
TI  - Medical applications and outcomes of bitangential scleral lenses.
AB  - PURPOSE: To evaluate the clinical results of a new scleral lens design with a
      bitangential (nonrotationally symmetrical) periphery. METHODS: All the necessary
      data were obtained during the 1-year study period. The bitangential scleral
      lenses were fitted and monitored according to a standardized fitting methodology.
      They were cut by precise submicron lathing from high-oxygen-permeable materials
      (including 10 scleral lenses from Menicon Z material). Subjective performance,
      visual acuity, and scleral lens-fitting characteristics were recorded after a
      median of 9.4 weeks (range, 3 weeks to 1 year). RESULTS: Diagnoses in the 213
      eyes (in 144 patients) were keratoconus (n = 121 eyes; 56.8%), ocular surface
      diseases (n = 31 eyes; 14.6%), penetrating keratoplasty (n = 29 eyes; 13.6%), and
      other forms of irregular astigmatism (n = 28 eyes; 13.1%). Many patients (164
      lenses; 77.0%) gave high ratings for comfort. The most common diameter was 20.0
      mm (162 lenses; 76.1%) (range, 18.5 to 21.5 mm). Median decimal best-corrected
      visual acuity with the bitangential scleral lenses was 0.8 (equivalent to Snellen
      20/25) (range, 0 to 1.5). Most bitangential scleral lenses showed good fitting
      characteristics: optimal values were seen for lens movement (208 lenses; 97.7%)
      and lens position (208 lenses; 97.7%). Median central corneal clearance was 0.2
      mm; clearances differed in the four peripheral directions. The median
      stabilization axis was 140 degrees (range, 0 to 180 degrees) in the right eyes
      and 60 degrees (range, 0 to 180 degrees) in the left eyes. CONCLUSIONS: The
      bitangential scleral lens-fitting and performance characteristics were clear and
      effective for the health professional and the patient. The high-oxygen-permeable
      material Menicon Z may, in theory, be of benefit to corneas with a high oxygen
      demand.

PMID- 23974665
TI  - Posterior subtenon injection of triamcinolone acetonide after phacoemulsification
      in a patient with X-linked retinoschisis.
AB  - PURPOSE: To describe a case of X-linked retinoschisis with pseudophakic cystoid
      macular edema treated by posterior subtenon injection of triamcinolone acetonide.
      CASE REPORT: The patient was a 60-year-old man. His best-corrected visual acuity
      (BCVA) was counting fingers in the right eye. Senile cataract was found with
      grade II nuclear sclerosis. Optical coherence tomography revealed foveoschisis
      with a central foveal thickness (CFT) of 545 MUm. The patient underwent
      uneventful phacoemulsification and in-the-bag implantation of intraocular lens.
      Postoperative persistent cystoid macular edema was found, with CFT increased to
      787 MUm. The macular edema did not respond to topical corticosteroids and
      nonsteroidal anti-inflammatory drugs. Triamcinolone acetonide 20 mg was injected
      into the posterior subtenon space 10 weeks after the surgery. Macular cystic
      lesions dramatically disappeared 2 months after the injection, and CFT decreased
      to 171 MUm, with accompanying inner/outer segment disruption. His BCVA also
      improved to 20/100. Macular edema or foveoschisis did not recur, and BCVA
      remained stable 1 year after the cataract operation. CONCLUSIONS: Foveoschisis
      and pseudophakic cystoid macular edema disappeared after posterior subtenon
      injection of triamcinolone acetonide without recurrence during the 15-month
      follow-up period.

PMID- 23974666
TI  - Whole-body SPECT/CT for bone scintigraphy: diagnostic value and effect on patient
      management in oncological patients.
AB  - PURPOSE: This study was designed to assess the additional value of SPECT/CT of
      the trunk used in conjunction with conventional nuclear imaging and its effects
      on patient management in a large patient series. METHODS: In 353 patients, whole
      body scintigraphy (WBS), SPECT, and SPECT/CT were prospectively performed for
      staging and restaging. SPECT/CT of the trunk was performed in all patients. In
      the 308 evaluable patients (211 with breast cancer, 97 with prostate cancer),
      clinical follow-up was used as the gold standard. Bone metastases were confirmed
      in 72 patients and excluded in 236. Multistep analyses per lesion and per patient
      were performed. Clinical relevance was expressed in terms of downstaging and
      upstaging rates on a per-patient basis. RESULTS: In the total patient group,
      sensitivities, specificities, and negative and positive predictive values on a
      per-patient basis were 93 %, 78 %, 95 % and 59 % for WBS, 94 %, 71 %, 97 % and 53
      % for SPECT, and 97 %, 94 %, 97 % and 88 % for SPECT/CT, respectively. In all
      subgroups, specificity and positive predictive value were significantly (p<0.01)
      better with SPECT/CT. Downstaging of metastatic disease in the total, breast
      cancer and prostate cancer groups using SPECT/CT was possible in 32.1 %, 33.8 %
      and 29.5 % of patients, respectively. Upstaging in previously negative patients
      by additional SPECT/CT was observed in three breast cancer patients (2.1 %).
      Further diagnostic imaging procedures for unclear scintigraphic findings were
      necessary in only 2.5 % of patients. SPECT/CT improved diagnostic accuracy for
      defining the extent of multifocal metastatic disease in 34.6 % of these patients.
      CONCLUSIONS: SPECT/CT significantly improved the specificity and positive
      predictive value of bone scintigraphy in cancer patients. In breast cancer
      patients, we found a slight increase in sensitivity. SPECT/CT had a significant
      effect on clinical management because of correct downstaging and upstaging,
      better definition of the extent of metastases, and a reduction in further
      diagnostic procedures.

PMID- 23974664
TI  - Intertester agreement in refractive error measurements.
AB  - PURPOSE: To determine the intertester agreement of refractive error measurements
      between lay and nurse screeners using the Retinomax Autorefractor and the
      SureSight Vision Screener. METHODS: Trained lay and nurse screeners measured
      refractive error in 1452 preschoolers (3 to 5 years old) using the Retinomax and
      the SureSight in a random order for screeners and instruments. Intertester
      agreement between lay and nurse screeners was assessed for sphere, cylinder, and
      spherical equivalent (SE) using the mean difference and the 95% limits of
      agreement. The mean intertester difference (lay minus nurse) was compared between
      groups defined based on the child's age, cycloplegic refractive error, and the
      reading's confidence number using analysis of variance. The limits of agreement
      were compared between groups using the Brown-Forsythe test. Intereye correlation
      was accounted for in all analyses. RESULTS: The mean intertester differences (95%
      limits of agreement) were -0.04 (-1.63, 1.54) diopter (D) sphere, 0.00 (-0.52,
      0.51) D cylinder, and -0.04 (1.65, 1.56) D SE for the Retinomax and 0.05 (-1.48,
      1.58) D sphere, 0.01 (-0.58, 0.60) D cylinder, and 0.06 (-1.45, 1.57) D SE for
      the SureSight. For either instrument, the mean intertester differences in sphere
      and SE did not differ by the child's age, cycloplegic refractive error, or the
      reading's confidence number. However, for both instruments, the limits of
      agreement were wider when eyes had significant refractive error or the reading's
      confidence number was below the manufacturer's recommended value. CONCLUSIONS:
      Among Head Start preschool children, trained lay and nurse screeners agree well
      in measuring refractive error using the Retinomax or the SureSight. Both
      instruments had similar intertester agreement in refractive error measurements
      independent of the child's age. Significant refractive error and a reading with
      low confidence number were associated with worse intertester agreement.

PMID- 23974667
TI  - Myocardial perfusion imaging in stable symptomatic patients with extensive
      coronary atherosclerosis.
AB  - PURPOSE: High coronary artery calcium (CAC) scores are associated with a high
      likelihood of ischaemia and obstructive coronary disease. Myocardial perfusion
      imaging (MPI) is a key investigation to determine the need for revascularization.
      However, the value of MPI in presence of extensive CAC has so far only been
      demonstrated in asymptomatic patients, whereas its value in symptomatic patients
      remains largely unclear. Therefore, we studied the impact of MPI in symptomatic
      patients with a CAC score >= 1,000. METHODS: We included 282 patients (mean age
      69 +/- 9 years, 63% men) without a history of coronary disease with suspected
      stable angina referred for MPI and with a CAC score >= 1,000. On follow-up at 18
      months invasive angiography, coronary revascularization, nonfatal myocardial
      infarction and death were recorded. RESULTS: MPI was normal in 54 %, equivocal in
      10 % and abnormal in 37 % (fixed defect 9 % and ischaemia 28 %) of patients. More
      abnormal MPI findings were observed in men, smokers and those with even higher
      CAC scores. During follow-up, 1 patient (with nonischaemic MPI) died from a
      cardiac cause, 1 patient (with ischaemic MPI) suffered a myocardial infarction
      and 92 patients (33 %) underwent revascularization. Ischaemia on MPI was a strong
      predictor of coronary revascularization (odds ratio 13.1; 95 % CI 7.1-24.3; p <
      0.001). CONCLUSION: Ischaemia on MPI is observed in approximately 30 % of
      patients with a CAC score >= 1,000, and is a strong predictor of coronary
      revascularization. However, nonischaemic MPI does not exclude revascularization,
      and patients with persisting complaints should be considered for invasive
      angiography.

PMID- 23974668
TI  - Insulin-like growth factor binding protein-2 (IGFBP-2) in Japanese flounder,
      Paralichthys olivaceus: molecular cloning, expression patterns and hormonal
      regulation during metamorphosis.
AB  - In this study, we cloned and characterized cDNA sequences of two insulin-like
      growth factor binding protein-2 (IGFBP-2a and IGFBP-2b) from Japanese flounder,
      Paralichthys olivaceus. The full-length cDNA of IGFBP-2a is 1,046 bp long and
      consists an open frame (ORF) of 876 bp, a 5'-untranslated region (UTR) of 125 bp
      and a 3'-UTR of 45 bp. IGFBP-2b is 1,067 bp, including a 5'-UTR of 53 bp, a 3'
      UTR of 198 bp and an ORF of 816 bp. Real-time quantitative PCR results revealed
      that IGFBP-2a -2b mRNA was expressed in all detected tissues. Interestingly, the
      levels of IGFBP-2a mRNA in all detected tissues were higher in female than male,
      but IGFBP-2b was precisely the opposite. At different embryonic stages, the
      levels of IGFBP-2a mRNA were typically higher than IGFBP-2b. After hatching,
      IGFBP-2a mRNA was gradually decreased to a relatively lower level. However, the
      expression of IGFBP-2b mRNA was increased after hatching, including 3, 7, 10, 14,
      17, 20 and 23 days post-hatching (dph), and it presents a higher level until 29
      (metamorphic climax), 36 (post-climax) and 41 dph (the end of metamorphosis). In
      levothyroxine sodium salt (T4, the main form of thyroid hormone in animals)
      treated and thiourea (TU)-treated larvae, the expressions of IGFBP-2a had not
      visibly changed, except in T4-treated 17 dph larvae. The expressions of IGFBP-2b
      mRNA were distinctly increased from 17 to 23 dph, but suddenly dropped to a lower
      level in and after 29 dph. However, the levels of IGFBP-2b mRNA during
      metamorphosis were greatly down-regulated after TU treatment. These results
      provided basic information for further studies on the role of IGF system in
      flatfish development and metamorphosis. 

PMID- 23974669
TI  - Anesthetic activity of the essential oil of Aloysia triphylla and effectiveness
      in reducing stress during transport of albino and gray strains of silver catfish,
      Rhamdia quelen.
AB  - This study investigated the efficacy of the essential oil (EO) of Aloysia
      triphylla as an anesthetic for albino and gray strains of silver catfish, Rhamdia
      quelen. Juveniles were exposed to concentrations between 20 and 800 MUL L(-1) EO
      of A. triphylla to evaluate time of induction and recovery from anesthesia. In
      another experiment, both strains were divided into four groups such as 0
      (control), 30, 40, or 50 MUL L(-1) EO and transported for 5 h. The longest time
      for anesthetic induction and recovery was observed in the albinos. Both strains
      reached anesthesia in the 100-800 MUL L(-1) (11.1-1.24 min) range, without
      mortality, being 200 MUL L(-1) the best response considering time to anesthesia
      (5.35 min). Albinos transported with all EO concentrations showed higher values
      of carbon dioxide in the water of transport, but lower levels were observed in
      grays transported with 40 and 50 MUL L(-1) EO when compared to control fish. The
      same concentrations did not prevent significant whole-body cortisol rise at the
      end of transport in the albino strain. Juveniles of both strains transported with
      EO presented lower ion loss to the water compared to control fish. The EO of A.
      triphylla is an effective anesthetic for albino and gray silver catfish. This EO
      increases whole-body cortisol levels in the albino strain, but as it reduces net
      ion loss as in the gray strain, it can be also recommended for transport.

PMID- 23974670
TI  - Oxidative stress and antioxidant enzymes activities in the African catfish,
      Clarias gariepinus, experimentally challenged with Escherichia coli and Vibrio
      fischeri.
AB  - The impacts of bacterial infection on cultivated fish species, African catfish,
      were investigated using oxidative stress biomarkers [lipid peroxidation (LPO) and
      protein carbonylation] and the activities of important antioxidant/detoxifying
      enzymes [catalase and glutathione S-transferase (GST)]. Fish were inoculated via
      oral gavage with one of the following treatments: 1 * 10(5) CFU/ml of Escherichia
      coli (EC1), 2 * 10(5) CFU/ml of E. coli (EC2), 1 * 10(5) CFU/ml of Vibrio
      fischeri (V1), 2 * 10(5) CFU/ml of V. fischeri (V2), gavaged with distilled water
      and not gavaged. Fish were maintained in the laboratory for 7 days after the
      bacterial inoculation, and the levels of LPO, protein carbonylation, GST, and
      catalase activities were determined in the muscle, gills, and liver of fish. Fish
      inoculated with bacteria (either E. coli or V. fischeri) had a significant higher
      levels of tissue LPO, protein carbonylation, and GST activities in a tissue
      specific pattern (liver > muscle > gills). This appears to be related with the
      levels of bacterial inoculation, with effects more pronounced in fish inoculated
      with either EC2 or V2. The catalase activity did not differ significantly between
      the inoculated and fish that were not inoculated. The results of this study
      indicate that bacterial inoculation could result in oxidative stress in fish, and
      liver has a higher rate of oxidative stress per mg tissue compared to the gills
      and the muscle.

PMID- 23974672
TI  - Real-time multiple human perception with color-depth cameras on a mobile robot.
AB  - The ability to perceive humans is an essential requirement for safe and efficient
      human-robot interaction. In real-world applications, the need for a robot to
      interact in real time with multiple humans in a dynamic, 3-D environment presents
      a significant challenge. The recent availability of commercial color-depth
      cameras allow for the creation of a system that makes use of the depth dimension,
      thus enabling a robot to observe its environment and perceive in the 3-D space.
      Here we present a system for 3-D multiple human perception in real time from a
      moving robot equipped with a color-depth camera and a consumer-grade computer.
      Our approach reduces computation time to achieve real-time performance through a
      unique combination of new ideas and established techniques. We remove the ground
      and ceiling planes from the 3-D point cloud input to separate candidate point
      clusters. We introduce the novel information concept, depth of interest, which we
      use to identify candidates for detection, and that avoids the computationally
      expensive scanning-window methods of other approaches. We utilize a cascade of
      detectors to distinguish humans from objects, in which we make intelligent reuse
      of intermediary features in successive detectors to improve computation. Because
      of the high computational cost of some methods, we represent our candidate
      tracking algorithm with a decision directed acyclic graph, which allows us to use
      the most computationally intense techniques only where necessary. We detail the
      successful implementation of our novel approach on a mobile robot and examine its
      performance in scenarios with real-world challenges, including occlusion, robot
      motion, nonupright humans, humans leaving and reentering the field of view (i.e.,
      the reidentification challenge), human-object and human-human interaction. We
      conclude with the observation that the incorporation of the depth information,
      together with the use of modern techniques in new ways, we are able to create an
      accurate system for real-time 3-D perception of humans by a mobile robot. 

PMID- 23974671
TI  - Effects of dietary selenium of organic form against lead toxicity on the
      antioxidant system in Cyprinus carpio.
AB  - In this study was evaluated potential protective effect of organic selenium (Se)
      on heavy metal stress induced by lead (Pb) in Cyprinus carpio. For this reason,
      C. carpio was exposed to sublethal concentration of Pb (1.5 mg/L Pb(NO3)2) for 14
      days. The fish were fed a basal (control; measured 0.55 mg/kg Se) diet or a basal
      diet supplemented with 2.50 mg/kg (measured 2.92 mg/kg Se) organic Se (Sel
      Plex((r))) during the experiment period. The variations in glutathione peroxidase
      (GSH-Px), glutathione S-transferase (GST) activities, and levels of reduced
      glutathione (GSH) with malondialdehyde (MDA) in liver and brain tissues of C.
      carpio were investigated in experimental groups. GSH levels in liver and brain
      tissues were significantly decreased by exposure to Pb. GST activity was
      significantly increased (p < 0.05) in liver tissue, but decreased in brain of
      treated fish by exposure to Pb. Also, GSH-Px activity was significantly increased
      in liver tissue, but decreased in brain of Pb-treated fish. Levels of MDA were
      increased in liver and brain of Pb-treated fish. The organic Se treatment for Pb
      intoxicated animals improved activities of GSH-Px, GST and levels of MDA within
      normal limits. Supplemented Se could be able to improve Pb-induced oxidative
      stress by decreasing lipid peroxidation and regulating antioxidant defense system
      in tissues.

PMID- 23974673
TI  - Tensor body: real-time reconstruction of the human body and avatar synthesis from
      RGB-D.
AB  - Real-time 3-D reconstruction of the human body has many applications in
      anthropometry, telecommunications, gaming, fashion, and other areas of human
      computer interaction. In this paper, a novel framework is presented for
      reconstructing the 3-D model of the human body from a sequence of RGB-D frames.
      The reconstruction is performed in real time while the human subject moves
      arbitrarily in front of the camera. The method employs a novel parameterization
      of cylindrical-type objects using Cartesian tensor and b-spline bases along the
      radial and longitudinal dimension respectively. The proposed model, dubbed tensor
      body, is fitted to the input data using a multistep framework that involves
      segmentation of the different body regions, robust filtering of the data via a
      dynamic histogram, and energy-based optimization with positive-definite
      constraints. A Riemannian metric on the space of positive-definite tensor splines
      is analytically defined and employed in this framework. The efficacy of the
      presented methods is demonstrated in several real-data experiments using the
      Microsoft Kinect sensor. 

PMID- 23974674
TI  - 'SIMPLES': a structured primary care approach to adults with difficult asthma.
AB  - The substantial majority of patients with asthma can expect minimal breakthrough
      symptoms on standard doses of inhaled corticosteroids with or without additional
      add-on therapies. SIMPLES is a structured primary care approach to the review of
      a person with uncontrolled asthma which encompasses patient education monitoring,
      lifestyle and pharmacological management and addressing support needs which will
      achieve control in most patients. The small group of patients presenting with
      persistent asthma symptoms despite being prescribed high levels of treatment are
      often referred to as having 'difficult asthma'. Some will have difficult,
      'therapy resistant' asthma, some will have psychosocial problems which make it
      difficult for them to achieve asthma control and some may prove to have an
      alternative diagnosis driving their symptoms. A few patients will benefit from
      referral to a 'difficult asthma' clinic. The SIMPLES approach, aligned with close
      co-operation between primary and specialist care, can identify this patient
      group, avoid inappropriate escalation of treatment, and streamline clinical
      assessment and management. 

PMID- 23974675
TI  - The Primary Care Respiratory Society-UK Quality Award: development and piloting
      of quality standards for primary care respiratory medicine.
AB  - In an attempt to improve the standards of primary respiratory care in the UK, the
      Primary Care Respiratory Society-UK (PCRS-UK), in conjunction with other leading
      respiratory-interested health professional and patient groups, has devised a
      General Practice Quality Award for Respiratory Medicine. The Award is divided
      into three modules separated into a total of seven clinical standards (in
      parentheses): 'Clinical' (prevention, early and accurate diagnosis, acute care,
      chronic care); 'Organisational' (equipment); and 'The Practice Team' (practice
      learning needs, educational strategy). Assessment is by submission of a written
      portfolio of 37 pieces of evidence including audit, reflective learning, patient
      feedback, and significant event analyses. The Award was piloted in five
      respiratory-interested practices across the UK. The practices reported
      improvements in practice organisation, practice teamwork, improved process
      measures such as improvement in quality of spirometry, and improved patient
      access to patient services. All practices in the UK are being invited to apply
      for the Award in 2013. It is hoped that it will provide a framework and stimulus
      for provision of high-quality primary respiratory care, not only in the UK, but
      also some aspects of the Award may be applicable on a wider international scale. 

PMID- 23974676
TI  - The genetics of asthma and allergic diseases: pieces of the puzzle are starting
      to come together.

PMID- 23974677
TI  - A sequence of methodological changes due to sequencing.
AB  - PURPOSE OF REVIEW: During the past 2 years, next-generation sequencing studies
      have revolutionized the field of genetic association studies. We review the
      concomitant evolution of statistical methods. RECENT FINDINGS: As much of the
      genetic variability identified with sequencing is extremely rare, many new
      methods have been developed for rare variant association studies. Sequencing data
      available as a result of large public projects are also being integrated with
      genome-wide association study (GWAS) chip data to improve genotype imputation. A
      further trend in recent methodological development has been the use of the linear
      mixed effect model (LMM). LMMs are used for rare variant association to handle
      effect heterogeneity. They are also used more generally in GWAS to account for
      population structure. SUMMARY: Many rare variant association tests have been
      developed to analyze the genetic variation discovered with large-scale DNA
      sequencing; however, no single approach outperforms others under all disease
      models and power tends to be low. Sequencing data are also contributing to
      improved imputation of uncommon genetic variants, although imputation of rare
      variants remains a challenge. The appropriate correction for population structure
      in rare variant analyses remains unclear; specialized adjustment techniques may
      be necessary.

PMID- 23974678
TI  - Involvement of lymphocytes in asthma and allergic diseases: a genetic point of
      view.
AB  - PURPOSE OF REVIEW: The activation and regulation of lymphocytes play a central
      role in asthmatic inflammation. It is increasingly recognized that diverse panels
      of lymphocyte lineages and cytokine profiles are involved in the asthmatic
      phenotypes. In this review, we discuss the advances in the gene variants
      associated with the regulation of lymphocytes and relevant cytokines underlying
      asthma and allergic diseases. We also discuss the current evidence about the
      epigenetic regulation of lymphocyte differentiation and the interaction with
      environment. RECENT FINDINGS: Many genetic variants in asthma are functionally
      associated with lymphocytes and relevant cytokines. Interleukin (IL)-2RB is
      important in the homeostasis of T regulatory cells (Tregs) through effects from
      IL-2. IL-18R1 and ST2/IL-1RL1 drive the T helper 1 and 2 inflammation via the
      ligands of their encoding receptors. Novel genes, like orosomucoid 1-like
      3/gasdermin-like gene and taste receptor type 2 members are being explored for
      their roles in T-cell activation. T-cell lineages are epigenetically regulated by
      de novo methyltransferases, histone methylase, CD44 and microRNA. Environmental
      factors such as second-hand smoke and ambient air pollution modify Tregs
      differentiation significantly. SUMMARY: Plenty of genetic loci of lymphocyte
      regulation provide us a deeper insight into the asthma pathogenesis. Future
      challenge is to define genetic drivers in asthma phenotypes to provide
      therapeutic targets.

PMID- 23974679
TI  - The role of eosinophils and basophils in allergic diseases considering genetic
      findings.
AB  - PURPOSE OF REVIEW: Basophils and eosinophils represent less than 1 and 5% of
      white blood cells, respectively. Their role in asthma and allergic inflammation
      remains incompletely defined. The present review addresses recent advances
      regarding the role of these two cell populations in allergic inflammation and
      asthma regarding both biological and genetic point of view. RECENT FINDINGS:
      Regarding eosinophils, the role of interleukin(IL)-25, IL-33 and thymic stromal
      lymphoprotein (TSLP) have been evidenced, and activation states of eosinophil
      beta1 and beta2 integrins have been found to correlate with the measurement of
      eosinophil recruitment and pulmonary function in asthma. New insights into the
      biology of basophils concern their role as regulators of Th2 cell response
      through IL-4 expression or the differentiation of monocytes to macrophages, and
      their population heterogeneity in human. The transcription factor PU.1 was
      reported to be involved in controlling transcription of specific genes both in
      eosinophils and basophils. Candidate genetic studies on eosinophils have explored
      genes involved in the intracellular calcium influx and apoptosis. At the genome
      wide level, studies identified genetic variants belonging to IL1RL1, TSLP and IL
      33, and four loci with pleiotropic effects on eosinophil and basophil counts
      [GATA2 (3q21), MHC (6p21), HBS1L-MYB (6q23), and ERG (21q22)]. SUMMARY: Recent
      findings from biological and genetic studies on eosinophils and basophils
      highlight the role of epithelial cell-derived cytokines such as TSLP and IL-33 in
      asthma and allergic diseases.

PMID- 23974680
TI  - Microbiome and skin diseases.
AB  - PURPOSE OF REVIEW: This article reviews recent findings on the skin microbiome.
      It provides an update on the current understanding of the role of microbiota in
      healthy skin and in inflammatory and allergic skin diseases. RECENT FINDINGS:
      Advances in computing and high-throughput sequencing technology have enabled in
      depth analysis of microbiota composition and functionality of human skin. Most
      data generated to date are related to the skin microbiome of healthy volunteers,
      but recent studies have also addressed the dynamics of the microbiome in diseased
      and injured skin. Currently, reports are emerging that evaluate the strategies to
      manipulate the skin microbiome, intending to modulate diseases and/or their
      symptoms. SUMMARY: The microbiome of normal human skin was found to have a high
      diversity and high interpersonal variation. Microbiota compositions of diseased
      lesional skin (in atopic dermatitis and psoriasis) showed distinct differences
      compared with healthy skin. The function of microbial colonization in
      establishing immune system homeostasis has been reported, whereas host-microbe
      interactions and genetically determined variation of stratum corneum properties
      might be linked to skin dysbiosis. Both are relevant for cutaneous disorders with
      aberrant immune responses and/or disturbed skin barrier function. Modulation of
      skin microbiota composition to restore host-microbiota homeostasis could be
      future strategies to treat or prevent disease.

PMID- 23974681
TI  - The impact of common metal allergens in daily devices.
AB  - PURPOSE OF REVIEW: We are widely exposed to metal allergens in our daily doings.
      As exposures constantly changes because of fashion trends and technological
      developments, there is a need for a continuous update of patch testers. An
      overview of consumer metal exposure studies that have been published in 2012 and
      2013 is provided as well as lists of common metal exposures. RECENT FINDINGS:
      Nickel release in concentrations that cause nickel allergy and contact dermatitis
      is seen from laptop computers. Cobalt is found in leather as a dye and may cause
      chronic dermatitis. Chromium is used as a dye and for tanning in leather items
      and is found in nearly all shoes and released from a high proportion. SUMMARY:
      New consumer items should continuously be considered and investigated for metal
      release when patients with positive patch test results to metal allergens are
      evaluated.

PMID- 23974682
TI  - Contact dermatitis in the cleaning industry.
AB  - PURPOSE OF REVIEW: The review summarizes recent findings on contact dermatitis in
      the cleaning industry. RECENT FINDINGS: Contact dermatitis is still an important
      issue in cleaning. Recent studies identified cleaning work sites and tasks, as
      well as specific cleaning products, which incur a risk increase for occupational
      contact dermatitis in cleaning. Workers involved in cleaning outdoors prevalence
      ratio [PR 1.85, 95% confidence interval (CI) 1.16-2.96], cleaning common areas of
      residential buildings (PR 1.77, 95% CI 1.11-2.84), schools (PR 1.84, 95% CI 1.15
      2.93) and cleaning building sites (PR 1.87, 95% CI 1.18-2.95) showed
      significantly higher rates of contact dermatitis. Relevant allergens in cleaning
      are rubber chemicals and disinfectants. Leading allergens are thiurams (11.6%,
      95% CI 9.1-14.1) and formaldehyde (3.4%, 95% CI 2.0-4.7), but contact with metal
      allergens might also be important. The most likely allergen sources for
      sensitization against rubber chemicals are protective gloves. High sensitization
      rates for disinfectants might result from the fact that employees in cleaning
      often use single-use medical examination gloves while cleaning. These gloves are
      not resistant to chemicals, which may break through the gloves within a short
      period of time, depending on glove material and thickness. No differences in
      sensitization rates and sensitization profiles were seen in cleaners of younger
      (<=40 years) and older (>40 years) age. SUMMARY: Prevalence of occupational
      contact dermatitis is still high in cleaning. Irritant contact dermatitis is
      prevailing, but allergic contact dermatitis is quite frequent, too. Up to now,
      prevention strategies in cleaning seem to be insufficient.

PMID- 23974683
TI  - Expression of antimicrobial peptides in atopic dermatitis and possible
      immunoregulatory functions.
AB  - PURPOSE OF REVIEW: To summarize the findings on the expression of antimicrobial
      peptides in the skin in inflammatory skin diseases and particularly in atopic
      dermatitis. Moreover, the literature addressing the functions of antimicrobial
      peptides (AMPs) beyond antimicrobial activities with impact on allergic skin
      inflammation is summarized as well. RECENT FINDINGS: Although lower expressed
      than in psoriasis, most AMPs have been shown to be either constitutively
      expressed or upregulated in atopic dermatitis as well. A number of
      immunoregulatory functions which might impact on allergic skin inflammation have
      been described for several antimicrobial peptides, mainly for human beta
      defensins and the cathelicidin LL-37. SUMMARY: From the recent literature, there
      is considerable evidence that AMPs are induced in the skin in atopic dermatitis.
      However, some studies suggest that the induction, release or mobilization of some
      AMPs in atopic dermatitis may not reach sufficient levels to provide adequate
      control of cutaneous microbial colonization. Th2 cytokines appear to negatively
      influence the expression and induction of some AMPs. A number of immunoregulatory
      functions have been described for several AMPs. Most of them point to a
      proinflammatory function of AMPs in addition to their antimicrobial activities.
      Further studies are needed to clarify the role of AMPs in atopic dermatitis.

PMID- 23974684
TI  - Allergic conjunctivitis: an update on diagnosis and management.
AB  - PURPOSE OF REVIEW: The focus of this review is to provide a logical paradigm for
      the diagnosis and treatment of ocular allergies, with a focus on seasonal
      allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC). RECENT
      FINDINGS: Several classes of topical medications are currently available for the
      management of ocular allergies, including: lubricating agents, vasoconstrictors,
      antihistamines, mast cell stabilizers, and topical corticosteroids. SUMMARY: SAC
      and PAC make up the vast majority of ocular allergy cases. A proactive approach
      to these diseases, anticipating the regional spring and fall allergen spikes, is
      needed for optimally managing these disorders. A multifaceted treatment regimen
      comprising patient education, lifestyle modification, and topical medications
      (such as antihistamines and/or mast cell stabilizers and corticosteroids) may be
      required in order to manage ocular allergies effectively. The appropriate
      treatment paradigm is based on the severity of the patients' signs and symptoms.
      For moderate-to-severe cases, especially chronic vernal keratoconjunctivitis,
      atopic keratoconjunctivitis, and giant papillary conjunctivitis, comanagement
      with an ophthalmologist is recommended.

PMID- 23974685
TI  - Immunomodulators for conjunctivitis.
AB  - PURPOSE OF REVIEW: Allergic conjunctivitis is an IgE-mediated inflammatory of
      conjunctiva. Despite the fact that histamine is a major mediator in this
      condition, use of topical antihistamines often gives only temporarily relief.
      Therapeutic agents aiming at inflammatory cascades of the disease are desirable
      particularly in cases with prolonged and severe allergic conjunctivitis. The
      article reviews these new treatment armamentariums with regard to their mechanism
      of actions and clinical efficacy. RECENT FINDINGS: Some second generation of
      antihistamines demonstrated anti-inflammatory properties such as inhibition of
      histamine release from mast cells as well as interference with the production
      cytokines and adhesion molecules from cord blood and conjunctival mast cells.
      Among these agents, ketotifen, epinastine and olopatadine are agents of major
      interest and are thus reviewed. Cromolyn, nedocromil, topical corticosteroids and
      immunotherapy, especially sublingual immunotherapy, are among other modes of
      therapy examined. Finally, the review focuses on cyclosporine A and tacrolimus,
      immunomodulators that have been extensively studied in the therapy of severe
      conjunctivitis such as atopic and vernal keratoconjunctivitis with promising
      results. SUMMARY: Several immunomodulatory options are currently available for
      treatment of allergic conjunctivitis. These therapeutic availabilities bring
      about a better therapeutic outcome for patients with allergic conjunctivitis,
      particularly those on the severe end of the spectrum.

PMID- 23974686
TI  - Is visual function affected in severe ocular allergies?
AB  - PURPOSE OF REVIEW: The purpose of the present review is to provide an overview on
      the clinical features and long-term complications of severe ocular allergies,
      with a special focus on the corneal involvement observed in these diseases, which
      may impair vision permanently. Furthermore, different treatment options are
      discussed based on the sight-threatening effects of corticosteroid use. RECENT
      FINDINGS: Recent data on the demographics, clinical and immunologic features of
      vernal and atopic keratoconjunctivitis are presented and discussed, and the
      evidence of a lack of literature addressing the issue of visual outcome in
      allergic diseases is underlined. The efficacy and possible long-term
      complications of their treatments are described, including visual impairment.
      SUMMARY: Diagnosis and treatment of patients with severe ocular allergy is a
      challenge for ophthalmologists due to the long-term corneal complications and the
      potential side-effects of topical corticosteroids that may induce cataract
      formation and glaucoma, and impair vision permanently. The review describes old
      and new concepts of management and possible complications such as severe, vision
      threatening forms of allergic ocular disease. An update on their management and
      long-term complications may help clinicians to establish a common agreement on
      treatment options and researchers to design future studies based on similar
      outcomes, including visual acuity.

PMID- 23974688
TI  - In-vivo confocal microscopy of the ocular surface: ocular allergy and dry eye.
AB  - PURPOSE OF REVIEW: To summarize recent studies on in-vivo confocal microscopy
      (IVCM) findings in ocular allergy and dry eye disease (DED), highlighting the
      role of IVCM in the advancement of knowledge of these diseases. RECENT FINDINGS:
      IVCM provided new data on ocular surface changes in both ocular allergy and DED.
      Corneal and conjunctival epithelial and inflammatory cells, corneal nerves, and
      Meibomian glands showed peculiar patterns of abnormalities, not easily
      discernable with current clinical exams in these two diseases and their subtypes.
      At present, small sample size of researches, and poor standardization and
      evidence of image analysis and interpretation are the most challenging issues.
      SUMMARY: Ocular allergy and DED are common and increasing healthcare problems,
      and need better understanding of pathogenesis and natural history, more reliable
      endpoints, and more tailored diagnostic and therapeutic approaches. IVCM allows
      quick, noninvasive, steady-state respectful examination of the ocular surface at
      cellular level to be performed and has potential to be used in the future as a
      biomarker and to contribute to optimize the tailored management of these
      diseases.

PMID- 23974687
TI  - The ocular surface epithelial barrier and other mechanisms of mucosal protection:
      from allergy to infectious diseases.
AB  - PURPOSE OF REVIEW: Studies completed in the last decade provide new insights into
      the role of the epithelial glycocalyx in maintaining ocular surface barrier
      function. This review summarizes these findings, their relevance to allergic and
      infectious disease, and highlights the potential benefits of exploiting the
      modulation of barrier integrity for therapeutic gain. RECENT FINDINGS: The
      molecular components sealing the space between adjacent ocular surface epithelial
      cells, such as tight junctions, have been extensively characterized, and their
      contribution to the paracellular barrier established. A second layer of
      protection - the transcellular barrier - is provided by transmembrane mucins and
      their O-glycans on the glycocalyx. Cell surface glycans bind carbohydrate-binding
      proteins to promote formation of complexes that are no longer thought to be a
      static structure, but, instead, a dynamic system that responds to extrinsic
      signals and modulates pathogenic responses. Although functioning as a protective
      mechanism to maintain homeostasis, the glycocalyx also restricts drug targeting
      of epithelial cells. SUMMARY: The traditional model of intercellular junctions
      protecting the ocular surface epithelia has recently been expanded to include an
      additional glycan shield that lines apical membranes on the ocular surface. A
      better understanding of this apical barrier may lead to better management of
      ocular surface disease.

PMID- 23974689
TI  - Pathophysiology of psoriasis.
AB  - Psoriasis is a chronic inflammatory papulosquamous disease characterized by
      multiple remissions and relapses. For long, it was believed to be primarily a
      disorder of keratinization. However, the successful use of traditional
      immunosupressants and newer immunomodulatory agents in the treatment of psoriasis
      led to the belief that psoriasis is primarily a disease of Th1 cell immune
      dysregulation. Recent developments have brought up several new findings such as
      the role of Th17 cells and evidence of skin barrier dysfunction in psoriasis,
      akin to atopic dermatitis. The present review aims to focus on these new
      developments and explain the pathogenesis of psoriasis on the basis of currently
      available information.

PMID- 23974690
TI  - Comorbidities in psoriasis.
AB  - Moderate to severe psoriasis is associated with concomitant diseases that may
      have a significant impact on patients. It is necessary for the treating physician
      to recognize these concomitant diseases, known as comorbidities, early as they
      influence the management options. Important comorbidities are psoriatic
      arthritis, metabolic syndrome, Crohn's disease, depression, and cancer. Patients
      with severe psoriasis may be at an increased risk for myocardial infarction and
      this subgroup of patients tends to have a reduced life expectancy. The presence
      of co-morbid diseases is associated with an increase in concomitant medication,
      some of which may worsen psoriasis; conversely, systemic treatment of psoriasis
      with certain drugs may impact the co-morbid conditions. As dermatologists are the
      primary health-care providers for psoriasis, adequate knowledge of comorbidities
      helps in choosing the appropriate therapy as well as timely intervention. 

PMID- 23974691
TI  - Diagnosis and management of psoriatic arthritis.
AB  - Psoriatic arthritis (PsA) is a multi-faceted disease marked by varying
      combinations of peripheral arthritis, dactylitis, spondylitis, and enthesitis.
      Rarely, recurrent uveitis occurs. Skin involvement may or may not exist. However,
      patients with nail psoriasis have a higher probability of developing PsA.
      Untreated patients have significant morbidity and mortality. Timely diagnosis and
      aggressive treatment of the disease can lead to lower morbidity. Drug therapy of
      PsA includes symptomatic therapy and therapy with disease-modifying anti
      rheumatic drugs. Biologics are the only agents that address all the pathological
      changes, of this chronic condition. 

PMID- 23974692
TI  - Infliximab: efficacy in psoriasis.
AB  - Moderate to severe psoriasis often needs to be addressed with standard disease
      modifying therapies such as methotrexate, cyclosporine, acitretin or ultraviolet
      radiation, which have their potential benefits and limitations. The tumor
      necrosis factor-alpha (TNF-alpha) is elevated in psoriatic plaques compared to
      non lesional skin as well as in the plasma of patients with moderate to severe
      psoriasis. Infliximab, a TNF-alpha blocker, has been recommended for the
      treatment of moderate to severe plaque psoriasis in adults who have failed to
      respond to these therapies or who cannot tolerate them. Its specific action on
      the bound and membrane forms of the pro-inflammatory cytokine TNF-alpha has made
      it the molecule of choice for obtaining quicker and longer remission in
      recalcitrant cases. However, the widespread use of infliximab in the Indian
      subcontinent is limited by its cost. This article reviews the international
      guidelines for use of infliximab, its dosage patterns, and efficacy in chronic
      plaque psoriasis, nail psoriasis, erythrodermic psoriasis, and pustular psoriasis
      as well as Indian experience. 

PMID- 23974693
TI  - Tumor necrosis factor-alpha antagonists: Side effects and their management.
AB  - As elevated levels of tumor necrosis factor-alpha (TNF-alpha) are associated with
      disease severity in psoriasis and psoriatic arthritis, TNF-alpha antagonists are
      being used to treat moderate to severe disease in patients who have
      contraindications, fail to respond or develop side effects to conventional
      systemic therapies. It is of utmost importance to be well versed with the
      possible adverse effects and contraindications of TNF-alpha antagonists so that
      they can be used effectively and safely. Many of their adverse effects have been
      well studied in patients of rheumatoid arthritis (RA) and inflammatory bowel
      disease (IBD) and may not be completely applicable in psoriasis. This is because
      patients with RA and IBD are on multiple immunosuppressants while those with
      psoriasis are mostly receiving single systemic therapy and often have
      comorbidities that distinguish them from those with RA or IBD. Also, some of the
      side effects are still controversial and debated. Long-term prospective
      randomized controlled studies are needed to better understand the associated risk
      in patients of psoriasis. Baseline screening and periodic monitoring during
      treatment can reduce and help in early identification and appropriate management
      of the adverse outcomes. This article reviews the side effects known to be
      associated with TNF-alpha antagonists, their pathomechanisms and management
      guidelines. Some of the common side effects include infusion and injection site
      reactions, infections particularly reactivation of tuberculosis, autoantibody
      formation and drug induced lupus erythematosus, liver function abnormalities,
      hematological, and solid organ malignancies. 

PMID- 23974694
TI  - Newer targeted therapies in psoriasis.
AB  - Psoriasis is a common, chronic, inflammatory skin disease that can have a
      significant impact on the quality of life of those who are afflicted due to
      chronicity of the disease and frequent remissions and relapses. Many available
      systemic therapies, however, are unsuitable for chronic administration due to the
      risk of cumulative toxicity. Recent advances in the understanding of the
      pathophysiology of psoriasis have led to the development of new, genetically
      engineered, targeted therapies for this disease. These include approaches
      targeting antigen presentation and co-stimulation, T-cell activation and
      leukocyte adhesion, action on pro-inflammatory mediators, and modulating the
      cytokine balance. Although only preliminary data are available so far and there
      is limited data supporting their use, these trials contribute to a further
      understanding of the disease and will eventually lead to new therapeutic options
      for psoriasis. 

PMID- 23974695
TI  - Targeting aberrant sialylation in cancer cells using a fluorinated sialic acid
      analog impairs adhesion, migration, and in vivo tumor growth.
AB  - Cancer cells decorate their surface with a dense layer of sialylated glycans by
      upregulating the expression of sialyltransferases and other glycogenes. Although
      sialic acids play a vital role in many biologic processes, hypersialylation in
      particular has been shown to contribute to cancer cell progression and
      metastasis. Accordingly, selective strategies to interfere with sialic acid
      synthesis might offer a powerful approach in cancer therapy. In the present
      study, we assessed the potential of a recently developed fluorinated sialic acid
      analogue (P-3F(ax)-Neu5Ac) to block the synthesis of sialoglycans in murine
      melanoma cells and the consequences on cell adhesion, migration, and in vivo
      growth. The results showed that P-3F(ax)-Neu5Ac readily caused depletion of
      alpha2,3-/alpha2,6-linked sialic acids in B16F10 cells for several days. Long
      term inhibition of sialylation for 28 days was feasible without affecting cell
      viability or proliferation. Moreover, P-3F(ax)-Neu5Ac proved to be a highly
      potent inhibitor of sialylation even at high concentrations of competing
      sialyltransferase substrates. P-3F(ax)-Neu5Ac-treated cancer cells exhibited
      impaired binding to poly-l-lysine, type I collagen, and fibronectin and
      diminished migratory capacity. Finally, blocking sialylation of B16F10 tumor
      cells with this novel sialic acid analogue reduced their growth in vivo. These
      results indicate that P-3F(ax)-Neu5Ac is a powerful glycomimetic capable of
      inhibiting aberrant sialylation that can potentially be used for anticancer
      therapy.

PMID- 23974697
TI  - BH3 mimetics: status of the field and new developments.
AB  - Targeting apoptosis is an attractive approach in cancer therapy. The BH3-only
      proteins of the BCL-2 family (having only the BCL-2 homology domain BH3) can
      trigger apoptosis by binding to the prosurvival members of this family and
      neutralizing their functional activity (sequestration of the proapoptotic Bcl-2
      family members). The "BH3 mimetic" concept has prompted the development of small
      molecules capable of mimicking BH3-only proteins and thus inducing apoptosis. The
      prototype BH3 mimetic ABT-737 selectively targets the three prosurvival proteins
      BCL-XL, BCL-2, and BCL-W (but not MCL-1 or A1) and its oral derivative ABT-263
      has proved promising in clinical trials. Some putative BH3 mimetics are also
      tested clinically while others are still being characterized. This article
      recapitulates the various known BH3 mimetics and presents the recent developments
      in the field. The latter include (i) the identification of molecular determinants
      responsible for the specific interactions between BH3 motifs and the binding
      grooves of prosurvival proteins and (ii) the characterization of new compounds
      and particularly BH3 mimetics that antagonize either selectively MCL-1 or BCL-2
      or a broad range of prosurvival proteins. These data are critical advances toward
      the discovery of novel anticancer agents.

PMID- 23974698
TI  - Influence of vestibular rehabilitation on neck pain and cervical range of motion
      among patients with whiplash-associated disorder: a randomized controlled trial.
AB  - OBJECTIVE: To describe how vestibular rehabilitation influences pain and range of
      motion among patients with whiplash-associated disorder and dizziness, and to
      describe whether pain or range of motion correlated with balance performance or
      self-perceived dizziness handicap. SUBJECTS: A total of 29 patients, 20 women and
      9 men, age range 22-76 years. METHODS: Patients with whiplash-associated disorder
      and dizziness were randomized to either intervention (vestibular rehabilitation)
      or control. Neck pain intensity, cervical range of motion (CROM), balance and
      self-perceived dizziness handicap were measured at baseline, 6 weeks and 3
      months. RESULTS: There were no differences in neck pain intensity or CROM between
      the 2 groups either at baseline, 6 weeks or 3 months (p = 0.10-0.89). At
      baseline, neck pain intensity correlated with CROM (-0.406) and self-perceived
      dizziness handicap (0.492). CROM correlated with self-perceived dizziness
      handicap and with 1 balance measure (-0.432). Neck pain intensity did not
      correlate with balance performance (-0.188-0.049). CONCLUSION: Neck pain
      intensity and CROM was not influenced by vestibular rehabilitation. Importantly,
      the programme did not appear to increase pain or decrease neck motion, as
      initially thought. Neck pain intensity and CROM correlated with self-perceived
      dizziness handicap. CROM also correlated with 1 balance measure.

PMID- 23974699
TI  - Chronological effects of rifampicin discontinuation on cytochrome P450 activity
      in healthy Japanese volunteers, using the cocktail method.
AB  - Cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A are major factors
      involved in the metabolism of clinically prescribed drugs. Because the time
      course after drug treatment discontinuation has received little attention, we
      aimed to clarify the chronological changes of rifampicin-induced CYP enzyme
      activities after rifampicin discontinuation. Thirteen volunteers took 450 mg of
      rifampicin once daily, and the cocktail method, which uses caffeine, losartan,
      omeprazole, dextromethorphan, and midazolam as CYP-specific probes, was
      repeatedly used for the evaluation of CYP levels. Concentrations of probes and
      metabolites were determined by liquid chromatography-tandem mass spectrometry.
      Seven-day rifampicin administration increased CYP2C19 and CYP3A enzyme
      activities. The induced CYP2C19 and CYP3A activities remained elevated at 4 days
      after rifampicin discontinuation and returned to baseline levels 8 days after
      rifampicin discontinuation. CYP1A2 and CYP2D6 enzyme activities showed no
      significant changes, and CYP2C9 enzyme activity was increased with rifampicin
      administration, with a tendency toward statistical significance. Drug
      interactions can occur even after rifampicin discontinuation. 

PMID- 23974700
TI  - Spectroscopic, viscositic and molecular modeling studies on the interaction of 3'
      azido-daunorubicin thiosemicarbazone with DNA.
AB  - A new daunorubicin has been synthesized and structurally characterized. The
      interaction of native calf thymus DNA (ctDNA) with 3'-azido-daunorubicin
      thiosemicarbazone (ADNRT) was investigated under simulated physiological
      conditions by multi-spectroscopic techniques, viscometric measurements and
      molecular modeling study. It concluded that ADNRT could intercalate into the base
      pairs of ctDNA, and the fluorescence quenching by ctDNA was static quenching
      type. Thermodynamic parameters calculated suggested that the binding of ADNRT to
      ctDNA was mainly driven by hydrophobic interactions. The relative viscosity of
      ctDNA increased with the addition of ADNRT, which confirmed the intercalation
      mode. Furthermore, molecular modeling studies corroborate the above experimental
      results. 

PMID- 23974701
TI  - Alternative Measures of Self-Rated Health for Predicting Mortality Among Older
      People: Is Past or Future Orientation More Important?
AB  - PURPOSE: The purpose of this study was to compare the prognostic validity of
      alternative measures of health ratings, including those that tap temporal
      reflections, on adult mortality. DESIGN AND METHODS: The study uses a national
      sample of 1,266 Americans 50-74 years old in 1995, with vital status tracked
      through 2005, to compare the effect of 3 types of health ratings on mortality:
      conventional indicator of self-rated health (SRH), age comparison form of SRH,
      and health ratings that incorporate temporal dimensions. Logistic regression was
      used to estimate the odds of mortality associated with alternative health ratings
      while adjusting for health conditions, lifestyle factors, and status
      characteristics and resources. RESULTS: Self-rated health was a consistent
      predictor of mortality, but the respondent's expected health rating-10 years in
      the future-was an independent predictor. Future health expectations were more
      important than past (recalled change) in predicting mortality risk: People with
      more negative expectations of future health were less likely to survive.
      IMPLICATIONS: The findings reveal the importance of future time perspective for
      older people and suggest that it is more useful to query older people about their
      future health expectations than about how their health has changed.

PMID- 23974702
TI  - Asymmetric inferior oblique anterior transposition for incomitant asymmetric
      dissociated vertical deviation.
AB  - BACKGROUND: Inferior oblique anterior transposition (IOAT) is indicated in
      patients with incomitant dissociated vertical deviation (DVD) larger in
      adduction. In general, bilateral surgery is recommended in patients with DVD
      unless there is deep monocular amblyopia. The purpose of this study is to
      evaluate the results of asymmetric IOAT in patients with asymmetric incomitant
      DVD larger in adduction. METHODS: Retrospective chart review of the records of
      all patients with incomitant asymmetric DVD associated with inferior oblique (IO)
      overaction who underwent asymmetric IO weakening procedure. In all patients, the
      eye with more DVD in adduction underwent IOAT to the temporal corner of the
      insertion of the inferior rectus (IR) muscle, and the eye with less DVD underwent
      IOAT to a position 3-4 mm posterior to the insertion of the IR. No other muscles
      were operated simultaneously. No patient had previous surgery on any
      cyclovertical extracular muscle. RESULTS: Fourteen patients were included. Mean
      age at surgery was 10.3 +/- 8.8 years (range 4-33). Primary position DVD
      preoperatively was 18 +/- 2 PD in the eye with the larger DVD compared to 1.1 +/-
      1.0 PD postoperatively (p < 0.0001). DVD asymmetry between the lateral gaze with
      the largest DVD and the lateral gaze with the smallest DVD was 9.8 +/- 3.1 PD
      (range 5-14 PD) preoperatively vs 1.1 +/- 1.0 PD (range 0-2 PD), (p < 0.0001).
      Ten patients had preoperative V-pattern >10 PD (24.7 +/- 8.7 PD, range 12-50 PD)
      preoperatively vs no patients postoperatively (mean V-pattern 4.4 +/- 2.0 PD), (p
      < 0.0001). Postoperative follow up was 1.6 +/- 0.7 years (range 1-3 years).
      CONCLUSION: In patients with asymmetric incomitant DVD, asymmetric IOAT improves
      lateral incomitance without increasing the risk of antielevation, limitation in
      upgaze rotation, or hypertropia, or worsening the DVD in the eye with less
      deviation preoperatively.

PMID- 23974703
TI  - Fractal analysis in radiological and nuclear medicine perfusion imaging: a
      systematic review.
AB  - OBJECTIVES: To provide an overview of recent research in fractal analysis of
      tissue perfusion imaging, using standard radiological and nuclear medicine
      imaging techniques including computed tomography (CT), magnetic resonance imaging
      (MRI), ultrasound, positron emission tomography (PET) and single-photon emission
      computed tomography (SPECT) and to discuss implications for different fields of
      application. METHODS: A systematic review of fractal analysis for tissue
      perfusion imaging was performed by searching the databases MEDLINE (via PubMed),
      EMBASE (via Ovid) and ISI Web of Science. RESULTS: Thirty-seven eligible studies
      were identified. Fractal analysis was performed on perfusion imaging of tumours,
      lung, myocardium, kidney, skeletal muscle and cerebral diseases. Clinically,
      different aspects of tumour perfusion and cerebral diseases were successfully
      evaluated including detection and classification. In physiological settings, it
      was shown that perfusion under different conditions and in various organs can be
      properly described using fractal analysis. CONCLUSIONS: Fractal analysis is a
      suitable method for quantifying heterogeneity from radiological and nuclear
      medicine perfusion images under a variety of conditions and in different organs.
      Further research is required to exploit physiologically proven fractal behaviour
      in the clinical setting. KEY POINTS: * Fractal analysis of perfusion images can
      be successfully performed. * Tumour, pulmonary, myocardial, renal, skeletal
      muscle and cerebral perfusion have already been examined. * Clinical applications
      of fractal analysis include tumour and brain perfusion assessment. * Fractal
      analysis is a suitable method for quantifying perfusion heterogeneity. * Fractal
      analysis requires further research concerning the development of clinical
      applications.

PMID- 23974704
TI  - MicroRNAs in cardiac regeneration and cardiovascular disease.
AB  - microRNAs (miRNAs) are a class of small non-coding RNAs, which have been shown
      important to a wide range of biological process by post-transcriptionally
      regulating the expression of protein-coding genes. miRNAs have been demonstrated
      essential to normal cardiac development and function. Recently, numerous studies
      indicate miRNAs are involved in cardiac regeneration and cardiac disease,
      including cardiac hypertrophy, myocardial infarction and cardiac arrhythmia.
      These observations suggest miRNAs play important roles in cardiology. In this
      review, we summarize the recent progress of studying miRNAs in cardiac
      regeneration and cardiac disease. We also discuss the diagnostic and therapeutic
      potential of miRNAs in heart disease. 

PMID- 23974706
TI  - GABA promotes the competitive selection of dendritic spines by controlling local
      Ca2+ signaling.
AB  - Activity-dependent competition of synapses plays a key role in neural
      organization and is often promoted by GABA; however, its cellular bases are
      poorly understood. Excitatory synapses of cortical pyramidal neurons are formed
      on small protrusions known as dendritic spines, which exhibit structural
      plasticity. We used two-color uncaging of glutamate and GABA in rat hippocampal
      CA1 pyramidal neurons and found that spine shrinkage and elimination were
      markedly promoted by the activation of GABAA receptors shortly before action
      potentials. GABAergic inhibition suppressed bulk increases in cytosolic Ca(2+)
      concentrations, whereas it preserved the Ca(2+) nanodomains generated by NMDA
      type receptors, both of which were necessary for spine shrinkage. Unlike spine
      enlargement, spine shrinkage spread to neighboring spines (<15 MUm) and competed
      with their enlargement, and this process involved the actin-depolymerizing factor
      ADF/cofilin. Thus, GABAergic inhibition directly suppresses local dendritic
      Ca(2+) transients and strongly promotes the competitive selection of dendritic
      spines. 

PMID- 23974705
TI  - A genome-wide association study of chronic otitis media with effusion and
      recurrent otitis media identifies a novel susceptibility locus on chromosome 2.
AB  - Chronic otitis media with effusion (COME) and recurrent otitis media (ROM) have
      been shown to be heritable, but candidate gene and linkage studies to date have
      been equivocal. Our aim was to identify genetic susceptibility factors using a
      genome-wide association study (GWAS). We genotyped 602 subjects from 143 families
      with 373 COME/ROM subjects using the Illumina Human CNV370-Duo DNA Bead Chip
      (324,748 SNPs). We carried out the GWAS scan and imputed SNPs at the regions with
      the most significant associations. Replication genotyping in an independent
      family-based sample was conducted for 53 SNPs: the 41 most significant SNPs with
      P < 10(-4) and 12 imputed SNPs with P < 10(-4) on chromosome 15 (near the
      strongest signal). We replicated the association of rs10497394 (GWAS discovery P
      = 1.30 * 10(-5)) on chromosome 2 in the independent otitis media population (P =
      4.7 * 10(-5); meta-analysis P = 1.52 * 10(-8)). Three additional SNPs had
      replication P values < 0.10. Two were on chromosome 15q26.1 including rs1110060,
      the strongest association with COME/ROM in the primary GWAS (P = 3.4 *10(-7)) in
      KIF7 intron 7 (P = 0.072), and rs10775247, a non-synonymous SNP in TICRR exon 2
      (P = 0.075). The third SNP rs386057 was on chromosome 5 in TPPP intron 1 (P =
      0.045). We have performed the first GWAS of COME/ROM and have identified a SNP
      rs10497394 on chromosome 2 is significantly associated with COME/ROM
      susceptibility. This SNP is within a 537 kb intergenic region, bordered by CDCA7
      and SP3. The genomic and functional significance of this newly identified locus
      in COME/ROM pathogenesis requires additional investigation. 

PMID- 23974707
TI  - Cocaine-induced structural plasticity in frontal cortex correlates with
      conditioned place preference.
AB  - Contextual cues associated with previous drug exposure can trigger drug craving
      and seeking, and form a substantial obstacle in substance use recovery. Using in
      vivo imaging in mice, we found that cocaine administration induced a rapid
      increase in the formation and accumulation of new dendritic spines, and that
      measures of new persistent spine gain correlated with cocaine conditioned place
      preference. Our data suggest that new persistent spine formation in the frontal
      cortex may be involved in stimulant-related learning driving appetitive behavior.

PMID- 23974708
TI  - Spontaneous cortical activity alternates between motifs defined by regional
      axonal projections.
AB  - Using millisecond-timescale voltage-sensitive dye imaging in lightly anesthetized
      or awake adult mice, we show that a palette of sensory-evoked and hemisphere-wide
      activity motifs are represented in spontaneous activity. These motifs can reflect
      multiple modes of sensory processing, including vision, audition and touch. We
      found similar cortical networks with direct cortical activation using
      channelrhodopsin-2. Regional analysis of activity spread indicated modality
      specific sources, such as primary sensory areas, a common posterior-medial
      cortical sink where sensory activity was extinguished within the parietal
      association area and a secondary anterior medial sink within the cingulate and
      secondary motor cortices for visual stimuli. Correlation analysis between
      functional circuits and intracortical axonal projections indicated a common
      framework corresponding to long-range monosynaptic connections between cortical
      regions. Maps of intracortical monosynaptic structural connections predicted
      hemisphere-wide patterns of spontaneous and sensory-evoked depolarization. We
      suggest that an intracortical monosynaptic connectome shapes the ebb and flow of
      spontaneous cortical activity. 

PMID- 23974709
TI  - Parthanatos mediates AIMP2-activated age-dependent dopaminergic neuronal loss.
AB  - The defining pathogenic feature of Parkinson's disease is the age-dependent loss
      of dopaminergic neurons. Mutations and inactivation of parkin, an ubiquitin E3
      ligase, induce Parkinson's disease through accumulation of pathogenic substrates.
      We found that transgenic overexpression of a parkin substrate, aminoacyl-tRNA
      synthetase complex interacting multifunctional protein-2 (AIMP2), led to a
      selective, age-dependent, progressive loss of dopaminergic neurons via activation
      of poly(ADP-ribose) polymerase-1 (PARP1). AIMP2 accumulation in vitro and in vivo
      resulted in PARP1 overactivation and dopaminergic cell toxicity via direct
      association of these proteins in the nucleus, providing a path to PARP1
      activation other than DNA damage. Inhibition of PARP1 through gene deletion or
      drug inhibition reversed behavioral deficits and protected against dopamine
      neuron death in AIMP2 transgenic mice. These data indicate that brain-permeable
      PARP inhibitors could effectively delay or prevent disease progression in
      Parkinson's disease. 

PMID- 23974710
TI  - GluA1 phosphorylation at serine 831 in the lateral amygdala is required for fear
      renewal.
AB  - Fear renewal, a widely pursued model of post-traumatic stress disorder and
      phobias, refers to the context-specific relapse of conditioned fear after
      extinction. However, its molecular mechanisms are largely unknown. We found that
      renewal-inducing stimuli, generally believed to be insufficient to induce
      synaptic plasticity, enhanced excitatory synaptic strength, activity of synaptic
      GluA2-lacking AMPA receptors and Ser831 phosphorylation of synaptic surface GluA1
      in the lateral nucleus of the amygdala (LAn) of fear-extinguished rats.
      Consistently, the induction threshold for LAn synaptic potentiation was
      considerably lowered after extinction, and renewal occluded this low-threshold
      potentiation. The low-threshold potentiation (a potential cellular substrate for
      renewal), but not long-term potentiation, was attenuated by dialysis into LAn
      neurons of a GluA1-derived peptide that competes with Ser831-phosphorylated
      GluA1. Microinjections of the same peptide into the LAn attenuated fear renewal,
      but not fear learning. Our findings suggest that GluA1 phosphorylation
      constitutes a promising target for clinical treatment of aberrant fear-related
      disorders. 

PMID- 23974711
TI  - DNA methylation regulates associative reward learning.
AB  - Reward-related memories are essential for adaptive behavior and evolutionary
      fitness, but they are also a core component of maladaptive brain diseases such as
      addiction. Reward learning requires dopamine neurons located in the ventral
      tegmental area (VTA), which encode relationships between predictive cues and
      future rewards. Recent evidence suggests that epigenetic mechanisms, including
      DNA methylation, are essential regulators of neuronal plasticity and experience
      driven behavioral change. However, the role of epigenetic mechanisms in reward
      learning is poorly understood. Here we show that the formation of reward-related
      associative memories in rats upregulates key plasticity genes in the VTA, which
      are correlated with memory strength and associated with gene-specific changes in
      DNA methylation. Moreover, DNA methylation in the VTA is required for the
      formation of stimulus-reward associations. These results provide the first
      evidence that that activity-dependent methylation and demethylation of DNA is an
      essential substrate for the behavioral and neuronal plasticity driven by reward
      related experiences. 

PMID- 23974712
TI  - Initiating inhaled steroid treatment for children with asthma in the emergency
      room: current reported prescribing rates and frequently cited barriers.
AB  - OBJECTIVE: The objective of this study was to determine how frequently emergency
      department (ED) physicians prescribe inhaled corticosteroids (ICSs) and describe
      commonly cited barriers. METHODS: We surveyed members of the American Academy of
      Pediatrics Section on Emergency Medicine between May and August 2011. Demographic
      data were collected. Using the knowledge-attitude-behavior model for barriers to
      physician guideline adherence, we asked 20 Likert scale questions regarding
      barriers to ICS prescribing. Our primary outcome was reported frequency of ICS
      prescribing. We defined frequent prescribers as those who prescribe ICS more than
      25% of the time. Logistic regression models were built for each barrier category
      and identified barriers that predict infrequent prescribing. RESULTS: Two hundred
      seven (19.5%) of the 1062 surveyed responded; 75.8% report prescribing ICS 25% of
      the time or less. For knowledge, those who agreed that the National Heart, Lung,
      and Blood Institute guidelines are not clear regarding the ED physician's role
      were less likely to be frequent prescribers compared with those who disagreed
      (adjusted odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11-0.90). For
      attitude, those who agreed it is not the role of the ED physician to prescribe
      long-term medications were less likely to be frequent prescribers (adjusted OR,
      0.12; 95% CI, 0.04-0.37). For behavior, those who agreed they do not routinely
      start long-term medications because they cannot see patients in follow-up were
      less likely to be frequent prescribers (adjusted OR, 0.21; 95% CI, 0.07-0.58).
      CONCLUSIONS: Emergency department physicians report low rates of ICS prescribing.
      Commonly cited barriers include unclear guidelines, believing that long-term
      medication prescribing is not within their role, and inability to see patients in
      follow-up. Addressing guideline discrepancies may improve preventive care
      delivery in the ED.

PMID- 23974713
TI  - Two hundred sixty pediatric emergency airway encounters by air transport
      personnel: a report of the air transport emergency airway management (NEAR VI: "A
      TEAM") project.
AB  - BACKGROUND: Effective airway management is the cornerstone of resuscitative
      efforts for any critically ill or injured patient. The role and safety of
      pediatric prehospital intubation is controversial, particularly after prior
      research has shown varying degrees of intubation success. We report a series of
      consecutive prehospital pediatric intubations performed by air-transport
      providers. METHODS: We retrospectively reviewed intubation flight records from an
      89-rotorcraft, multistate emergency flight service during the time period from
      January 1, 2007, to December 31, 2009. All patients younger than 15 years were
      included in our analysis. We characterized patient, flight, and operator
      demographics; intubation methods; success rates; rescue techniques; and adverse
      events with descriptive statistics. We report proportions with 95% confidence
      intervals and differences between groups with Fisher exact and chi tests; P <
      0.05 was considered significant. RESULTS: Two hundred sixty pediatric intubations
      were performed consisting of 88 medical (33.8%) and 172 trauma (66.2%) cases;
      98.8% (n = 257) underwent an orotracheal intubation attempt as the first method.
      First-pass intubation success was 78.6% (n = 202), and intubation was ultimately
      successful in 95.7% (n = 246) of cases. Medical and trauma intubations had
      similar success rates (98% vs 95%, Fisher exact test P = 0.3412). There was no
      difference in intubation success between age groups (chi = 0.26, P = 0.88). Three
      patients were managed primarily with an extraglottic device. Rescue techniques
      were used in 11 encounters (4.2%), all of which were successful. Cricothyrotomy
      was performed twice, both successful. CONCLUSIONS: Prehospital pediatric
      intubation performed by air-transport providers, using rapid sequence intubation
      protocols, is highly successful. This effect on patient outcome requires further
      study.

PMID- 23974714
TI  - Enhancing the emergency department approach to pediatric sexual assault care:
      implementation of a pediatric sexual assault response team program.
AB  - OBJECTIVES: The objectives of this study were to describe the experience of a
      novel pediatric sexual assault response team (SART) program in the first 3 years
      of implementation and compare patient characteristics, evaluation, and treatment
      among subpopulations of patients. METHODS: This was a retrospective chart review
      of a consecutive sample of patients evaluated at a pediatric emergency department
      (ED) who met institutional criteria for a SART evaluation. Associations of
      evaluation and treatment with sex, menarchal status, and presence of injuries
      were measured using logistic regression. RESULTS: One hundred eighty-four
      patients met criteria for SART evaluation, of whom 87.5% were female; mean age
      was 10.1 (SD, 4.6) years. The majority of patients underwent forensic evidence
      collection (89.1%), which varied by menarchal status among girls (P < 0.01), but
      not by sex. Evidence of acute anogenital injury on physical examination was found
      in 20.6% of patients. As per the Centers for Disease Control and Prevention
      guidelines for acute sexual assault evaluations in pediatric patients, menarchal
      girls were more likely to undergo testing for sexually transmitted infections and
      pregnancy (P < 0.01) and to be offered pregnancy, sexually transmitted infection,
      and HIV prophylaxis (P < 0.01). CONCLUSIONS: In an effort to improve quality and
      consistency of acute sexual assault examinations in a pediatric ED, development
      of a SART program supported the majority of eligible patients undergoing forensic
      evidence collection. Furthermore, a substantial number of patients had evidence
      of injury on examination. These findings underscore the importance of having
      properly trained personnel to support ED care for pediatric victims of acute
      sexual assault.

PMID- 23974715
TI  - What role does body mass index play in hospital admission rates from the
      pediatric emergency department?
AB  - BACKGROUND: The primary objective of this study was to determine if children with
      abnormal body mass index (BMI) percentiles for age were admitted to the hospital
      from the emergency room at greater frequency than normal-weight children. This
      study also sought to evaluate what specific diagnoses both underweight and
      overweight children were being admitted with, and if a discrepancy exists.
      METHODS: A prospective observational chart review was conducted of children
      evaluated in the emergency department of the Children's Hospital at the
      University of Oklahoma during the month of October 2011 (n = 1747). One thousand
      nine hundred thirteen patient charts were reviewed, but 166 were excluded because
      of inability to obtain a height or weight within a 3-month period of the child
      being seen in the emergency department. RESULTS: Thirty-five (24.5%) of
      underweight patients, 82 (14.6%) of overweight or obese, and 173 (16.6%) of the
      normal-weight patients were admitted to the hospital from the emergency
      department. The underweight patients were admitted more frequently than the
      normal-weight (P = 0.0206) and overweight or obese patients (P = 0.0046). In
      addition, underweight patients were admitted more frequently with respiratory
      infections than normal-weight (P = 0.0279) and overweight or obese (P = 0.0509)
      patients. In addition, underweight patients were admitted more than overweight or
      obese patients with fractures (P = 0.0278). There was no statistical difference
      between overweight or obese and normal-weight admissions within any of the
      diagnostic categories. CONCLUSIONS: Underweight children (BMI <=5%) have an
      increased risk of hospitalization from the emergency department, even when
      adjusted for age and sex. In particular, hospitalization among underweight
      patients was increased for those patients with respiratory infections and
      fractures. No difference was seen between admission rates of overweight (BMI
      >=85%) or obese (BMI >=95%) patients from those of normal-weight patients. This
      warrants the need to counsel patients and their families on the dangers not only
      of obesity, but also of being underweight. Emphasis should be placed on healthy
      lifestyles that include well-balanced meals and exercise.

PMID- 23974716
TI  - Violating traditional NPO guidelines with PO contrast before sedation for
      computed tomography.
AB  - BACKGROUND: Administration of PO contrast within 2 hours before sedation for
      abdominal computed tomography (CT) is controversial because it violates American
      Society of Anesthesiologists guidelines that recommend 2 hours of fasting for
      clear fluids before sedation. OBJECTIVE: This study aimed to review the
      administration of PO contrast for patients undergoing propofol sedation for
      abdominal CT and to evaluate the impact of violation of traditional 2-hour NPO
      guidelines on care. METHODS: Sedation records were reviewed from January 2010 to
      October 2011 from all patients who received PO contrast within 2 hours of
      propofol sedation for abdominal CT. A control group of patients receiving
      intravenous contrast only before propofol sedation and abdominal CT was reviewed.
      Demographics, time between PO contrast administration and sedation, and amount of
      PO contrast were recorded. Outcome measures including success of sedation and
      adverse events (vomiting, suctioning, use of O2 or advanced airway, unplanned
      admissions) were recorded. RESULTS: Eighty-five patients received PO contrast
      within 2 hours before sedation for abdominal CT; 21 controls were identified. No
      differences in demographics or outcome measures were seen. No significant
      differences were seen in rates of interventions or adverse outcomes between
      groups. Median time between the successive PO contrast doses and propofol
      administration was 1.6 hours and 0.6 hours. CONCLUSIONS: Administering oral
      contrast material within 2 hours of propofol sedation for abdominal CT in
      children seems to be relatively safe compared with those sedated after
      traditional NPO time frames.

PMID- 23974717
TI  - Parental language and dosing errors after discharge from the pediatric emergency
      department.
AB  - OBJECTIVES: Safe and effective care after discharge requires parental education
      in the pediatric emergency department (ED). Parent-provider communication may be
      more difficult with parents who have limited health literacy or English-language
      fluency. This study examined the relationship between language and discharge
      comprehension regarding medication dosing. METHODS: We completed a prospective
      observational study of the ED discharge process using a convenience sample of
      English- and Spanish-speaking parents of children 2 to 24 months presenting to a
      single tertiary care pediatric ED with fever and/or respiratory illness. A
      bilingual research assistant interviewed parents to ascertain their primary
      language and health literacy and observed the discharge process. The primary
      outcome was parental demonstration of an incorrect dose of acetaminophen for the
      weight of his or her child. RESULTS: A total of 259 parent-child dyads were
      screened. There were 210 potential discharges, and 145 (69%) of 210 completed the
      postdischarge interview. Forty-six parents (32%) had an acetaminophen dosing
      error. Spanish-speaking parents were significantly more likely to have a dosing
      error (odds ratio, 3.7; 95% confidence interval, 1.6-8.1), even after adjustment
      for language of discharge, income, and parental health literacy (adjusted odds
      ratio, 6.7; 95% confidence interval, 1.4-31.7). CONCLUSIONS: Current ED discharge
      communication results in a significant disparity between English- and Spanish
      speaking parents' comprehension of a crucial aspect of medication safety. These
      differences were not explained purely by interpretation, suggesting that
      interventions to improve comprehension must address factors beyond language
      alone.

PMID- 23974718
TI  - Spontaneous pneumomediastinum: analysis of 87 pediatric patients.
AB  - OBJECTIVES: Early reports on pneumomediastinum studied the adult population, and
      recent analyses of pneumomediastinum in pediatric patients contain small numbers
      of patients. We aimed to summarize the experience of a larger number of pediatric
      patients with spontaneous pneumomediastinum (SPM) in a tertiary children's
      facility in northern Taiwan. METHODS: We performed a retrospective chart review
      of clinical manifestations and outcome of SPM on pediatric patients who were
      admitted to our hospital during a 10-year period. RESULTS: Forty-three patients
      (49.4%) had primary SPM, with a male predominance in adolescents. None of the 16
      patients younger than 6 years had primary SPM; 43 of 71 patients older than 6
      years had secondary SPM (0% vs 60.6%, P < 0.05). The common causes of secondary
      SPM were asthmatic exacerbation, pneumonia or lower respiratory tract infections,
      or choking. Ten patients had normal frontal chest radiograph finding
      (sensitivity, 89.1%); the lateral neck radiographs clearly demonstrated
      subcutaneous emphysema in 9 of these 10 patients. CONCLUSIONS: All patients
      younger than 6 years with SPM were secondary; therefore, they should be
      vigilantly examined for predisposing causes. For adolescent patients with SPM
      with no catastrophic events, asthma with exacerbation should be considered first,
      and extensive or invasive diagnostic examinations are not needed. Primary SPM
      usually requires conservative treatment only with no sequel or recurrence.
      Lateral neck radiograph has a higher sensitivity for the demonstration of
      subcutaneous emphysema in doubtful cases.

PMID- 23974719
TI  - Clinical accuracy of tympanic thermometer and noncontact infrared skin
      thermometer in pediatric practice: an alternative for axillary digital
      thermometer.
AB  - INTRODUCTION: The aim of this study was to compare the body temperature
      measurements of infrared tympanic and forehead noncontact thermometers with the
      axillary digital thermometer. METHODS: Randomly selected 50 pediatric patients
      who were hospitalized in Dr Behcet Uz Children's Training and Research Hospital,
      Pediatric Infectious Disease Unit, between March 2012 and September 2012 were
      included in the study. Body temperature measurements were performed using an
      axillary thermometer (Microlife MT 3001), a tympanic thermometer (Microlife Ear
      Thermometer IR 100), and a noncontact thermometer (ThermoFlash LX-26). RESULTS:
      Fifty patients participated in this study. We performed 1639 temperature readings
      for every method. The average difference between the mean (SD) of both axillary
      and tympanic temperatures was -0.20 degrees C (0.61 degrees C) (95% confidence
      interval, -1.41 degrees C to 1.00 degrees C). The average difference between the
      mean (SD) of both axillary and forehead temperatures was -0.38 (0.55 degrees C)
      (95% confidence interval, -1.47 degrees C to 0.70 degrees C). The Bland-Altman
      plot showed that most of the data points were tightly clustered around the zero
      line of the difference between the 2 temperature readings. With the use of the
      axillary method as the criterion standard, positive likelihood ratios were 17.9
      and 16.5 and negative likelihood ratios were 0.2 and 0.4 for tympanic and
      forehead measurements, respectively. DISCUSSION: The results demonstrated that
      the infrared tympanic thermometer could be a good option in the measurement of
      fever in the pediatric population. The noncontact infrared thermometer is very
      useful for the screening of fever in the pediatric population, but it must be
      used with caution because it has a high value of bias.

PMID- 23974720
TI  - Efficacy of postoperative adjuvant transfusion of cytokine-induced killer cells
      combined with chemotherapy in patients with colorectal cancer.
AB  - PURPOSE: To assess the activity and safety of postoperative adjuvant
      immunotherapy with transfusion of cytokine-induced killer (CIK) cells combined
      with chemotherapy in patients with colorectal cancer. METHODS: We retrospectively
      studied 96 consecutive patients with colorectal cancer who were treated with
      resection between January 2010 and December 2012 as well as adjuvant
      chemotherapy. Twenty-one of these patients accepted at least 1 cycle of CIK cell
      transfusion for immunotherapy (CIK group). Disease free survival (DFS), immune
      cells and treatment related side effects were assessed. The patients were
      followed up until May 2013. RESULTS: By the end of follow-up, 10 patients (10.42
      %) had died. Eighteen patients (18.75 %) had withdrawn. All the patients in the
      CIK group are still alive, and only 1 patient had withdrawn. Patients in the CIK
      group had significantly longer DFS than those in the control group [HR = 0.28, 95
      % CI (0.09, 0.91), p = 0.034]. The 2-year DFS rates of patients in the CIK group
      and the control group were 59.65 +/- 24.80 % and 29.35 +/- 6.39 %, respectively.
      The CD4(+)/CD8(+) ratios were significantly lower during the period of
      chemotherapy than those before chemotherapy (p = 0.0038), while the ratios were
      significantly higher during the period of CIK cell transfusion than those before
      CIK therapy (p = 0.0484). There were no immediate adverse reactions to the CIK
      cell transfusions. CONCLUSION: Adjuvant transfusion of CIK cells prolongs DFS in
      patients with colorectal cancer.

PMID- 23974721
TI  - DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is an immunogenic target
      of cancer stem cells.
AB  - Accumulating evidence suggests that most solid malignancies consist of
      heterogeneous tumor cells and that a relatively small subpopulation, which shares
      biological features with stem cells, survives through potentially lethal stresses
      such as chemotherapy and radiation treatment. Since the survival of this
      subpopulation of cancer stem cells (CSC) plays a critical role in recurrence, it
      must be eradicated in order to cure cancer. We previously reported that
      vaccination with CD133(+) murine melanoma cells exhibiting biological CSC
      features induced CSC-specific effector T cells. These were capable of eradicating
      CD133(+) tumor cells in vivo, thereby curing the parental tumor. In the current
      study, we indicated that DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked
      (DDX3X) is an immunogenic protein preferentially expressed in CD133(+) tumor
      cells. Vaccination with DDX3X primed specific T cells, resulting in protective
      and therapeutic antitumor immunity. The DDX3X-primed CD4(+) T cells produced
      CD133(+) tumor-specific IFNgamma and IL-17 and mediated potent antitumor
      therapeutic efficacy. DDX3X is expressed in various human cancer cells, including
      lung, colon, and breast cancer cells. These results suggest that anti-DDX3X
      immunotherapy is a promising treatment option in efforts to eradicate CSC in the
      clinical setting. 

PMID- 23974722
TI  - Investigating the candidacy of a lipoteichoic acid-based glycoconjugate as a
      vaccine to combat Clostridium difficile infection.
AB  - A lipoteichoic acid has recently been shown to be conserved in the majority of
      strains from Clostridium difficile and as such is being considered as a possible
      vaccine antigen. In this study we examine the candidacy of the conserved
      lipoteichoic acid by demonstrating that it is possible to elicit antibodies
      against C. difficile strains following immunisation of rabbits and mice with
      glycoconjugates elaborating the conserved lipoteichoic acid antigen. The present
      study describes a conjugation strategy that utilises an amino functionality,
      present at approximately 33 % substitution of the N-acetyl-glucosamine residues
      within the LTA polymer repeating unit, as the attachment point for conjugation. A
      maleimide-thiol linker strategy with the maleimide linker on the carboxyl
      residues of the carrier protein and the thiol linker on the carbohydrate was
      employed. Immunisation derived antisera from rabbits and mice, recognised all
      strains of C. difficile vegetative cells examined, despite an immune response to
      the linkers also being observed. These sera recognised live cells in an
      immunofluorescence assay and were also able to recognise the spore form of the
      bacterium. This study has illustrated that the LTA polymer is a highly conserved
      surface polymer of C. difficile that is easily accessible to the immune system
      and as such merits consideration as a vaccine antigen to combat C. difficile
      infection.

PMID- 23974723
TI  - Global workspace dynamics: cortical "binding and propagation" enables conscious
      contents.
AB  - A global workspace (GW) is a functional hub of binding and propagation in a
      population of loosely coupled signaling elements. In computational applications,
      GW architectures recruit many distributed, specialized agents to cooperate in
      resolving focal ambiguities. In the brain, conscious experiences may reflect a GW
      function. For animals, the natural world is full of unpredictable dangers and
      opportunities, suggesting a general adaptive pressure for brains to resolve focal
      ambiguities quickly and accurately. GW theory aims to understand the differences
      between conscious and unconscious brain events. In humans and related species the
      cortico-thalamic (C-T) core is believed to underlie conscious aspects of
      perception, thinking, learning, feelings of knowing (FOK), felt emotions, visual
      imagery, working memory, and executive control. Alternative theoretical
      perspectives are also discussed. The C-T core has many anatomical hubs, but
      conscious percepts are unitary and internally consistent at any given moment.
      Over time, conscious contents constitute a very large, open set. This suggests
      that a brain-based GW capacity cannot be localized in a single anatomical hub.
      Rather, it should be sought in a functional hub - a dynamic capacity for binding
      and propagation of neural signals over multiple task-related networks, a kind of
      neuronal cloud computing. In this view, conscious contents can arise in any
      region of the C-T core when multiple input streams settle on a winner-take-all
      equilibrium. The resulting conscious gestalt may ignite an any-to-many broadcast,
      lasting ~100-200 ms, and trigger widespread adaptation in previously established
      networks. To account for the great range of conscious contents over time, the
      theory suggests an open repertoire of binding coalitions that can broadcast via
      theta/gamma or alpha/gamma phase coupling, like radio channels competing for a
      narrow frequency band. Conscious moments are thought to hold only 1-4 unrelated
      items; this small focal capacity may be the biological price to pay for global
      access. Visuotopic maps in cortex specialize in features like color, retinal
      size, motion, object identity, and egocentric/allocentric framing, so that a
      binding coalition for the sight of a rolling billiard ball in nearby space may
      resonate among activity maps of LGN, V1-V4, MT, IT, as well as the dorsal stream.
      Spatiotopic activity maps can bind into coherent gestalts using adaptive
      resonance (reentry). Single neurons can join a dominant coalition by phase tuning
      to regional oscillations in the 4-12 Hz range. Sensory percepts may bind and
      broadcast from posterior cortex, while non-sensory FOKs may involve prefrontal
      and frontotemporal areas. The anatomy and physiology of the hippocampal complex
      suggest a GW architecture as well. In the intact brain the hippocampal complex
      may support conscious event organization as well as episodic memory storage. 

PMID- 23974724
TI  - Cortical thickness in children receiving intensive therapy for idiopathic apraxia
      of speech.
AB  - Children with idiopathic apraxia experience difficulties planning the movements
      necessary for intelligible speech. There is increasing evidence that targeted
      early interventions, such as Prompts for Restructuring Oral Muscular Phonetic
      Targets (PROMPT), can be effective in treating these disorders. In this study, we
      investigate possible cortical thickness correlates of idiopathic apraxia of
      speech in childhood, and changes associated with participation in an 8-week block
      of PROMPT therapy. We found that children with idiopathic apraxia (n = 11), aged
      3-6 years, had significantly thicker left supramarginal gyri than a group of
      typically-developing age-matched controls (n = 11), t(20) = 2.84, p <= 0.05. Over
      the course of therapy, the children with apraxia (n = 9) experienced significant
      thinning of the left posterior superior temporal gyrus (canonical Wernicke's
      area), t(8) = 2.42, p <= 0.05. This is the first study to demonstrate experience
      dependent structural plasticity in children receiving therapy for speech sound
      disorders.

PMID- 23974725
TI  - Electrophysiological correlates of connotative meaning in healthy children.
AB  - The affective, connotative meaning of words can be statistically quantified by
      the semantic differential technique. Words that are located clearly on one of the
      three dimensions called "Evaluation", "Potency", and "Activity" were used as
      visual stimuli in a topographic event related potential study (ERP). Stimuli had
      been statistically defined in a group of 249 children (Skrandies, Jpn Psychol Res
      53: 65-76, 2011). We investigated electrical brain activity in 19 healthy
      children with normal intelligence and reading skills between 11 and 15 years of
      age. Words that belonged to different semantic classes were presented at random
      on a monitor, and EEG was measured from 30 channels. Evoked potentials were
      computed offline for each semantic class. In the ERP data we observed significant
      effects of word class on component latency, field strength and topography.
      Similar as with adult subjects such effects occurred at small latency of about
      115 ms after word presentation. The language-evoked components in children were
      similar but not identical to those reported previously for various groups of
      adults. Our data show that visually evoked brain activity is modulated by
      connotative meaning of the stimuli at early processing stages not only in adults
      but also in children.

PMID- 23974726
TI  - Store-operated Ca2+ channels blockers inhibit lipopolysaccharide induced
      astrocyte activation.
AB  - The destruction of calcium homeostasis is an important factor leading to
      neurological diseases. Store-operated Ca(2+) (SOC) channels are essential for
      Ca(2+) homeostasis in many cell types. However, whether SOC channels are involved
      in astrocyte activation induced by lipopolysaccharide (LPS) still remains
      unknown. In this study, we used LPS as an exogenous stimulation to investigate
      the role of SOC channels in astrocyte activation. Using calcium imaging
      technology, we first found that SOC channels blockers, 1-[h-[3-(4
      methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole (SKF-96365) and 2
      aminoethyldiphenyl borate (2-APB), inhibited LPS induced [Ca(2+)]i increase,
      which prompted us to speculate that SOC channels may be involved in LPS induced
      astrocyte activation. Further experiments confirmed our speculation shown as SOC
      channels blockers inhibited LPS induced astrocyte activation characterized as
      cell proliferation by MTS and BrdU assay, raise in glial fibrillary acidic
      protein expression by immunofluorescence and Western Blot and secretion of
      interleukin 6 (IL-6) and interleukin 1beta (IL-1beta) by ELISA. So, our studies
      showed that SOC channels are involved in LPS-induced astrocyte activation.

PMID- 23974728
TI  - How to build a yeast nucleus.
AB  - Biological functions including gene expression and DNA repair are affected by the
      3D architecture of the genome, but the underlying mechanisms are still unknown.
      Notably, it remains unclear to what extent nuclear architecture is driven by
      generic physical properties of polymers or by specific factors such as proteins
      binding particular DNA sequences. The budding yeast nucleus has been intensely
      studied by imaging and biochemical techniques, resulting in a large quantitative
      data set on locus positions and DNA contact frequencies. We recently described a
      quantitative model of the interphase yeast nucleus in which chromosomes are
      represented as passively moving polymer chains. This model ignores the DNA
      sequence information except for specific constraints at the centromeres,
      telomeres, and the ribosomal DNA (rDNA). Despite its simplicity, the model
      accounts for a large majority of experimental data, including absolute and
      relative locus positions and contact frequency patterns at chromosomal and
      subchromosomal scales. Here, we also illustrate the model's ability to reproduce
      observed features of chromatin movements. Our results strongly suggest that the
      dynamic large-scale architecture of the yeast nucleus is dominated by statistical
      properties of randomly moving polymers with a few sequence-specific constraints,
      rather than by a large number of DNA-specific factors or epigenetic
      modifications. In addition, we show that our model accounts for recently measured
      variations in homologous recombination efficiency, illustrating its potential for
      quantitatively understanding functional consequences of nuclear architecture. 

PMID- 23974730
TI  - The end of the road for prostate specific antigen testing?
AB  - Many candidate biomarkers for diagnosis of prostate cancer have been
      investigated, but prostate-specific antigen (PSA) testing remains the frontline
      test for both mass screening and individual clinical testing. Although the PSA
      test is cost-effective, analytically reliable, and flexibly high throughput, it
      has a very weak correlation with prostate malignancy. This has resulted in over
      diagnosis and over-treatment of patients leading to costly economic, social, and
      psychological impacts. PSA testing lacks the ability to molecularly characterize
      prostate diseases and define aggressiveness and lethality, which are necessary to
      influence choice of treatment. Therefore, newer molecular tests are beginning to
      replace the PSA tests. The prostate cancer antigen 3 test has shown superiority
      and is now widely used. The recently reported sarcosine urine test, the already
      delineated TMPRSS2: ETS fusion genes, the glutathione-S-transferase P1 serum
      marker, and enhancer of zeste homolog 2 biomarker may also help improve diagnosis
      and prognostication of prostate cancer. The analytical trend is toward a
      multiplex testing format using molecular and/or proteomic techniques that are
      reliable, accurate, reproducible, and ensure rapid quantitation. Therefore,
      validation of these newer biomarkers and their assays are necessary for both
      large-scale clinical trials and clinical utility. 

PMID- 23974729
TI  - Developmental regulation of linkers of the nucleoskeleton to the cytoskeleton
      during mouse postnatal retinogenesis.
AB  - Sun proteins and Nesprins are two families of proteins whose direct interactions
      across the nuclear envelope provide for the core of Linkers of the Nucleoskeleton
      to the Cytoskeleton (LINC complexes) that physically connect the nucleus interior
      to cytoskeletal networks. Whereas LINC complexes play essential roles in nuclear
      migration anchorage and underlie normal CNS development, the developmental
      regulation of their composition remains largely unknown. In this study, we
      examined the spatiotemporal expression of lamins, Sun proteins and Nesprins
      during postnatal mouse retinal development. Whereas retinal precursor cells
      mostly express B-type lamins, Sun1, and high molecular weight isoforms of
      Nesprins, post-mitotic retinal cells are characterized by a drastic
      downregulation of the latter, the expression of A-type lamins, and the strong
      induction of a specific isoform of Nesprin1 late in retinal development.
      Importantly, our results emphasize different spatiotemporal expression for
      Nesprin1 and Nesprin2 and further suggest an important role for KASH-less
      isoforms of Nesprin1 in the CNS. In conclusion, the transition from retinal
      precursor cells undergoing interkinetic nuclear migration to post-mitotic retinal
      cells undergoing nuclear translocation and/or anchorage is accompanied by a
      profound remodeling of LINC complexes composition. This remodeling may reflect
      different requirements of nuclear dynamics at different stages of CNS
      development. 

PMID- 23974731
TI  - Relationship among expression of basic-fibroblast growth factor, MTDH/astrocyte
      elevated gene-1, adenomatous polyposis coli, matrix metalloproteinase 9,and COX-2
      markers with prognostic factors in prostate carcinomas.
AB  - BACKGROUND: The etiopathogenesis of prostate cancer (PC) is still not clear, but
      hormonal, genetic, and environmental factors are thought to play a role in the
      tumor pathogenesis. Astrocyte elevated gene-1(AEG-1) as a novel transmembrane
      protein is predominantly located in the perinuclear region and endoplasmic
      reticulum. It has been found that AEG-1 upregulation increases the invasive
      ability of glioma and prostate cancer. Basic fibroblast growth factor (bFGF),
      matrix metalloproteinase-9 (MMP-9), cyclooxygenases-2 (COX-2), and adenomatous
      polyposis coli (APC) are very important in tumor progression as well. MATERIALS
      AND METHODS: This study included 97 radical prostatectomy specimens. IHC stains
      for bFGF, MMP-9, COX-2, APC, and AEG-1 were performed on the tissue microarray
      using standard procedures. For each patient, the age, Gleason score, tumor
      volume, lymphovascular invasion, lymph node metastasis, surgical margin, and the
      invasion of vesiculoseminalis areas were assessed. Analyses were performed using
      the statistical PASW (ver. 18). RESULTS: Statistically significant positive
      relationships were found MMP-9 and COX-2 (r = 0.242 and P = 0.017), between MMP-9
      and APC (r = 0.207 and P = 0.043), and between bFGF and AEG-1 (r = 0.295 and P =
      0.004). However, the relationships between age and staining results and tumor
      volume and staining results were not found to be significant. Although a positive
      correlation was found between the Gleason score and tumor volume and the Gleason
      score and age (r = 0.415 and P = 0.0001; r = 0.246 and P = 0.015, respectively),
      we did not find a statistically significant relationship between other stains and
      other prognostic parameters (lymphovascular invasion, lymph node metastasis,
      surgical margin, or vesiculoseminalis invasion). CONCLUSION: The relationships we
      found between MMP-9 and COX-2, between MMP-9, and APC and between bFGF and AEG-1
      as independent prognostic parameters could be helpful in the development of new
      therapeutic procedures.

PMID- 23974732
TI  - A comparative study of heart rate variability tests and lipid profile in healthy
      young adult males and females.
AB  - BACKGROUND: Coronary Heart Disease (CHD) is the leading cause of death in many
      developed countries. The relation between heart rate variability (HRV) and CHD
      was recently explored after the development of HRV techniques. Lower HRV was
      proven to be associated with a greater risk for developing hypertension among
      normotensive men, and hypertension is one of the major risk factors of CHD. Acute
      myocardial infarction is accompanied by decreased HRV, which is due to reduced
      vagal or increased sympathetic outflow to the heart. AIM: This study was designed
      to test the hypothesis of influence of gender and lipid profile difference on
      heart rate variability tests. MATERIALS AND METHODS: Thirty healthy adult male
      and thirty healthy adult female subjects in the age group of 18- 25 years without
      any addictions and gross systemic disease were selected. Heart rate variability
      tests during Valsalva maneuver, deep breathing and 30:15 R-R intervals ratio were
      carried and lipid profile of the subjects were analyzed. RESULTS: We found a
      decrease in values of HRV tests during the Valsalva maneuver, deep breathing in
      male individuals as compared with age- and Body Mass Index, BMI-matched females.
      VHeart Rate Variability tests during 30:15 R-R intervals Ratio in male
      individuals were significantly decreased as compared with females. Values of
      total cholesterol, Low Density Lipoprotein, LDL cholesterol were found to be
      significantly increased and High Density Lipoprotein, HDL cholesterol
      significantly decreased in males. CONCLUSION: Healthy adult males may be at a
      higher risk of developing acute myocardial infarction and CHD due to decreased
      HRV and atherogenic lipid profile. Lower level of serum estrogen may be the cause
      of this difference in HRV among males. The difference in HRV tests among males
      and females disappears after menopause.

PMID- 23974733
TI  - Morphological spectrum of non-neoplastic lesions of the uterine cervix in Warri,
      South-South, Nigeria.
AB  - BACKGROUND: The uterine cervix is a gateway to several non-neoplastic and
      neoplastic gynecological lesions. Most of these non-neoplastic lesions are
      commonly found in women of reproductive age. These lesions constitute a source of
      morbidity and mortality in women worldwide hence the need to analyze them to
      provide a baseline data of the pattern of these lesions in our local environment.
      OBJECTIVE: The purpose of this study is to determine the frequency and
      morphological patterns of non-neoplastic cervical lesions at the central
      hospital, Warri, Nigeria. MATERIALS AND METHODS: All uterine cervical biopsies
      received at the Department of Pathology, Central Hospital, Warri over a 7 year
      period (January 2005-December 2011) were the specimens for this study. Slides
      were retrieved from the archives of the Department of Pathology. Where necessary,
      new sections were made from formalin fixed, paraffin embedded blocks. RESULTS: A
      total of 176 cervical specimens were received in the Pathology Department during
      this period. Of these, 56.3% were benign lesions while 43.7% were malignant.
      Among the benign cases, non-neoplastic lesions accounted for 92.9% of benign
      cervical lesions. The age range of non-neoplastic cervical lesions was 20 to 89
      years with a mean age of 54.9 +/- 4.6 years. The peak age incidence of non
      neoplastic cervical lesion was 40-49 years which accounted for 33.7%.
      Inflammatory lesions and tumor-like lesions accounted for 59.8% and 40.2% of non
      neoplastic cervical lesions respectively. Among the inflammatory lesions, chronic
      non-specific cervicitis was the most commonly encountered lesion constituting
      72.2% of all inflammation. Human papilloma virus (HPV) cervicitis with koilocytic
      changes accounted for 14.5% of all inflammatory lesions. CONCLUSION: Inflammatory
      lesions were the most frequent non-neoplastic cervical lesions. These lesions
      therefore account for significant amount of gynecological problems in our
      environment. Adequate cervical screening with follow up histological biopsies is
      a relevant tool in diagnosing them to enhance early detection of premalignant and
      malignant cervical lesions.

PMID- 23974734
TI  - Observational assessment and correlates to blood pressure of future physicians of
      Bengal.
AB  - INTRODUCTION: Hypertension is a modern day epidemic and growing public health
      problem. A sizable proportion of world populations suffer from prehypertension or
      hypertension. OBJECTIVES: The present study was carried out to detect the
      prevalence of undiagnosed hypertension among undergraduate medical students and
      to identify the associated risk factors. MATERIALS AND METHODS: The study was
      observational in nature and was done in medical colleges of Bengal. Study tool
      was a predesigned, pretested, validated, and semi-structured questionnaire
      containing both open-ended and close-ended questions. Data were collected through
      self-administration, clinical, and anthropometric examination. The data were then
      tabulated, analyzed and interpretation was done by using percentage and Chi
      square test. RESULTS: Most of the students (63%) were young adults, predominantly
      males (67%) and day scholars (71%). Almost one-third of them either suffered from
      hypertension or at risk of hypertension. Hypertension was found higher among male
      students. Family history of hypertension or diabetes mellitus was not associated
      with hypertension. Vegetarian or nonvegetarian diet or extra-salt consumption was
      also not associated with hypertension. Smoking was shown positively associated
      with hypertension but alcohol consumption was not. Higher per capita monthly
      income and overweight or obesity were shown positively associated with
      hypertension. CONCLUSION: The overall prevalence of hypertension in this study
      was 13% and there were positive association of hypertension with multiple socio
      demographic factors like age, sex, type of family, per capita monthly income,
      residence, BMI, smoking, etc.

PMID- 23974735
TI  - The frequency of various indications for plain chest radiography in Nnamdi
      Azikiwe University Teaching Hospital, Nnewi (NAUTH).
AB  - BACKGROUND: With soaring advances in the field of medicine, the place of older
      radiologic imaging modalities is being reduced to basic screening tools. Yet the
      modern imaging modalities like computerized tomography (CT), magnetic resonance
      imaging (MRI), ultrasound and nuclear medicine are hardly available. STUDY
      OBJECTIVES: To study the frequency of various indications of plain chest
      radiography, remind us of its uses and to enhance the preparedness of the
      department to maximally accomplish the ideals of this investigation. METHODOLOGY:
      A total of 1476 consecutive patients for chest radiography in the department of
      radiology, NAUTH, Nnewi from the period of February 2009 and whose request form
      contain adequate data were recruited for this study. These data were analyzed
      using SSPS. RESULTS: A total of 1476 patient were included in this study. There
      was female preponderance with male to female ratio of 1.3:1. Mean Age of the
      patients is 39.32 years (std19.56). The most frequent indication for chest
      radiography is certain infections and parasitic diseases (40.9% and the greatest
      source of referral for this study is General outpatient (GOPD)/family medicine
      department. CONCLUSION: The most frequent indications for chest radiography in
      the study are certain infection and parasitic diseases. Chest Radiography is the
      most frequent plain radiography study in our environment where infectious
      diseases are still very rampant. This makes chest radiography an important study
      for screening patient for possible diagnosis and classifying the need for further
      radiographic investigation of our patients.

PMID- 23974736
TI  - Risk factors for surgical site infections following clean orthopaedic operations.
AB  - BACKGROUND: Surgical site infections can follow clean orthopaedic operations and
      can cause serious morbidity, mortality and increased resource utilization.
      Despite this, there are few studies on risk factors for surgical site infections
      in the Nigerian orthopaedic literature. We conducted a prospective study to
      determine the host and environmental risk factors for surgical site infections
      following clean orthopaedic operations. MATERIALS AND METHODS: Consecutive
      patients who satisfied the inclusion criteria and were to undergo clean
      orthopaedic operations performed at the National Orthopaedic Hospital, Igbobi,
      Lagos from January 2007 to July 2008 were included. Patient's biodata, duration
      of preoperative hospitalization and other risk factors were analyzed. The risk
      factors for surgical site infection were determined with Chi square test.
      RESULTS: The overall rate of surgical site infection during the 18 months of the
      study was 9.9% (12 of 121). Independent risk factors for this were: Prolonged
      duration of preoperative hospital stay greater than 13 days (21% infection rate),
      increasing age greater than 60 years (31% infection rate), and use of implants
      and drains (only one un-drained wound was infected). CONCLUSION AND
      RECOMMENDATIONS: Patient's age, duration of preoperative hospitalization, type of
      surgery (implant or non-implant), and use of drains were the most significant
      risk factors affecting surgical site infection. It is recommended that
      preoperative hospital stay should be as short as possible and extra
      care/precautions taken when working on the elderly, using implants or requiring
      drainage.

PMID- 23974737
TI  - Clinical significance of low serum magnesium in pregnant women attending the
      University of Benin Teaching Hospital.
AB  - OBJECTIVE: Magnesium level is known to decline during pregnancy. A suggested role
      for magnesium deficiency in conditions like pre-eclampsia and pre-term birth has
      prompted studies with conflicting evidence. The primary objective of this study
      was to determine the prevalence of hypomagnesemia in pregnancy, while the
      secondary objectives attempted to define maternal and fetal outcome due to
      hypomagnesemia. SUBJECTS AND METHODS: A pilot study was performed to determine
      the mean serum magnesium level for the population of female patients attending
      the University of Benin Teaching Hospital. The result of the pregnant population
      in the pilot study was used as a reference for hypomagnesemia in this study.
      Thereafter, a prospective cohort study of antenatal women recruited in the second
      trimester and followed-up till delivery and 1 week post-partum was done. Serum
      magnesium estimates were done with samples collected at recruitment and delivery.
      The magnesium levels determined at recruitment were used to divide the subjects
      into two groups of hypomagnesemic and normomagnesemic patients. Their
      sociodemographic and clinical characteristics were used to generate a database
      for analysis. RESULTS: The prevalence of magnesium deficiency was 16.25%.
      Hypomagnesemia was significantly correlated with the occurrence of pre-eclampsia
      ( P = 0.011), leg cramps ( P = 0.000) and pre-term birth ( P = 0.030). A logistic
      regression analysis showed that hypomagnesemia had an Odds ratio of 22 for pre
      eclampsia. There was no maternal mortality or early neonatal death. CONCLUSION:
      Pre-eclampsia and pre-term birth are associated with hypomagnesemia in pregnancy;
      hence, magnesium supplementation or magnesium-rich diet consisting of green leafy
      vegetables, soy milk and legumes may improve outcome.

PMID- 23974738
TI  - Factors affecting utilization of university health services in a tertiary
      institution in South-West Nigeria.
AB  - BACKGROUND: Most university health services have extensive health
      infrastructures, for the provision of effective and efficient health services to
      the students. In this study, we have tried to determine student's perception of
      factors affecting their utilization. OBJECTIVE: To determine students' perception
      of health care services provided in a tertiary institution and assess students'
      attitude towards utilization. MATERIALS AND METHODS: Simple random sampling
      technique was used to select 540 respondents, comprising of 390 males and 150
      females. A structured and self-administered questionnaire was the instrument used
      to collect data for the study, while data collected was analyzed using
      descriptive statistics of frequency count and percentage. RESULTS: High cost of
      drugs (72.0%), non availability of essential drugs (54.8%), time spent waiting
      for treatment (67.2%), inadequate referral services (81.7%), and satisfaction
      with services (60.6%) were considered by the respondents as factors affecting the
      utilization of university health services. Students-medical staff relationship
      and accessibility to health facility (77.6% and 74.3% respectively) were,
      however, not considered as factors that affect utilization of university health
      services. CONCLUSION: It is recommended that to improve utilization and cost of
      care, government should make necessary efforts to incorporate tertiary
      institution into National Health Insurance scheme so that students above the age
      of 18 years can benefit from free treatment.

PMID- 23974739
TI  - Presence of chaperones during pelvic examinations in southeast Nigeria: women's
      opinions, attitude, and preferences.
AB  - OBJECTIVES: To assess the opinions, attitude, and preferences of Nigerian women
      to the presence of chaperones during pelvic examinations. MATERIALS AND METHODS:
      A cross-sectional survey of first time gynecology clinic attendees on their
      opinions, attitudes, and preferences with respect to the presence of chaperones
      during their pelvic examinations. The interview was conducted with the aid of
      semi-structured, researcher-administered questionnaires. RESULTS: One hundred and
      nineteen (51.7%) of the respondents preferred female physicians for pelvic
      examination, 23 (10%) preferred male physicians and 88 (38.3%) had no gender
      preference. When the examining physician is a male, 124 (53.9%) respondents would
      like to have chaperones during pelvic examinations while 106 (46.1%) would not.
      Eighty-three percent of respondents preferred nurse chaperones. Age, level of
      education, and parity did not have any significant relationship with the attitude
      of the respondents toward the presence of chaperones ( P = 0.503, 0.525, and
      0.605 respectively). CONCLUSIONS: We conclude that most southeastern Nigerian
      women would prefer their pelvic examinations to be done by a female physician or
      to be attended by a nurse chaperone if the examining physician is a male. We
      recommend a routine offer of chaperones during such examinations while respecting
      the patients' right to refuse the offer.

PMID- 23974740
TI  - Pattern and clinical profile of children with complex cardiac anomaly at
      University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu State, Nigeria.
AB  - BACKGROUND: Complex congenital cardiac abnormalities are rare among children and
      contribute to mortality and morbidity. The prevalence and pattern of presentation
      vary from place to place. MATERIALS AND METHODS: The objective of this study was
      to determine the clinical profile and pattern of presentation of complex
      congenital cardiac malformations among children attending a tertiary hospital in
      Enugu State. A cross-sectional retrospective study in which a review of the
      records of children who attended the children outpatient clinic of University of
      Nigeria Teaching Hospital (UNTH), Ituku-Ozalla, Enugu State over a 5-year period
      (January 2007-June 2012) was undertaken. RESULTS: Thirty one thousand seven
      hundred and ninety-five (31,795) children attended the outpatient clinic of the
      hospital over the study period, of these, 65 had cardiac diseases, from which 16
      were found to have congenital complex cardiac abnormalities of various types,
      giving a prevalence of 0.05%. Complex abnormalities seen in these children are
      Tricuspid atresia with various associations, cor triatriatum, single ventricle,
      and large ASD (atrio-septal defect) with complete AVCD, cor triatriatum sinistrum
      with cardiomyopathy, DORV (double outlet right ventricle) with left sided aorta,
      hypoplastic tricuspid valve with a PDA (patent ductus artriosus), TOF (tetralogy
      of fallot), prolapse of aortic valve, and pulmonary regurgitation. One of these
      complex cardiac anomalies presented with Turner's syndrome and another with
      VACTERAL association. CONCLUSIONS: The results of this study show that 0.05% of
      children who presented at cardiology clinic of a teaching hospital in Enugu State
      had congenital complex cardiac abnormalities and that the commonest forms seen
      were those with cor triatriatum and TOF.

PMID- 23974741
TI  - Intra-cardiac masses in adults: a review of echocardiogram records at two
      echocardiographic laboratories in Enugu, South-East Nigeria.
AB  - BACKGROUND: Transthoracic echocardiography (TTE) is an excellent initial
      diagnostic technique used to evaluate and diagnose cardiac masses, even though
      transoesophageal echocardiography (TEE) provides superior image resolution and
      better visualization of cardiac masses, especially in patients with suboptimal
      transthoracic echocardiographic studies. TTE is the clinical procedure of choice
      for identification of left ventricular thrombi. TTE has greater than 90%
      sensitivity and greater than 85% specificity for detection of left ventricular
      thrombi and is probably superior to the sensitivity and specificity of TEE,
      especially for apical thrombi. AIMS: The study aimed to identify the common types
      of cardiac masses and their commonest locations in the heart. MATERIALS AND
      METHODS: We did a retrospective review of our echocardiogram reports from May
      2003 to July 2012 to identify the frequency of intra-cardiac masses in adults, as
      well as the gender distribution and commonest location of these masses. RESULTS:
      There were 2,814 echo examinations in adults over this period, comprising 1,661
      males (59.1%) and 1,153 females (40.9%). Intra-cardiac masses were found in 20 of
      these patients representing 0.7% of the study population. Thrombi were the
      commonest masses noted in our study, and there were more masses in the atria than
      in the ventricles. The left heart chambers also had more masses than the right
      heart chambers. There was no sex difference in the frequency of cardiac masses.
      CONCLUSION: Intra-cardiac masses are rare, and transthoracic echocardiography is
      still valuable in the diagnosis and initial characterization of cardiac masses.

PMID- 23974742
TI  - Tobacco use and oral health of inmates in a Nigerian prison.
AB  - OBJECTIVES: To determine the effect of tobacco use on oral health status of
      inmates of a federal prison in Enugu, Nigeria. MATERIALS AND METHODS: The study
      involved 230 inmates of the Nigerian Prison in Enugu. An interviewer-administered
      questionnaire was used to collect data on the demographic characteristics of the
      participants, oral hygiene methods, and smoking habits. An intra-oral examination
      to determine their oral health status was done using simplified oral hygiene
      index (OHI-S) for the oral hygiene status, the modified decayed missing and
      filled teeth (DMFT) index for caries status, and community periodontal index of
      treatment needs (CPITN) for the periodontal needs. Statistical Package for Social
      Sciences software, version 15 was used to analyze data. RESULTS: One hundred and
      twenty participants (52.2%) were current smokers. Mean DMFT of smokers and
      nonsmokers were 2.38 +/- 0.71 and 2.25 +/- 0.83 respectively ( P = 0.508) while
      mean Community Periodontal Index (CPI) scores of smokers and nonsmokers were 4.71
      +/- 1.26 and 2.27 +/- 0.86, respectively ( P = 0.276). Oral soft tissue lesions
      such as mucosal burn, oral leukoplakia-like lesions were found mainly in the
      tobacco users. CONCLUSION: Tobacco use had a negative effect on the oral health
      of the participants as smokers had worse oral health profile than non-smokers.
      They may benefit from counseling programs with the view to educate them on the
      effect of tobacco use on oral health and by extension, the general health. The
      full implementation of the Framework Convention on Tobacco Control (FCTC) treaty
      in Nigeria could help in curtailing these unwanted consequences of tobacco use.

PMID- 23974743
TI  - Perception of patients attending a tertiary hospital in Nigeria about good dental
      practice: a pilot study.
AB  - BACKGROUND: Criteria for a good dental practice as expressed by patients have
      influence on their behavior in terms of compliance with clinical advice, less
      pain and anxiety and more utilization of dental care. OBJECTIVE: To assess the
      opinion of patients attending the dental clinic of a tertiary hospital
      Southwestern, Nigeria about their perception of a good dental practice. MATERIALS
      AND METHODS: A 16 item semi-structured bi-lingual interviewer-administered
      questionnaire comprising socio-demographic characteristics and 24 criteria of a
      good dental practice generated by clinicians and patients was administered to 156
      patients who were blinded from knowing which criteria were clinicians' or
      patients' criteria. Patients were then asked to pick 12 criteria out of the 24
      criteria that they considered of greater priority. Frequency of the most picked
      criteria in a descending order was determined. Student's t-test was used to
      compare mean scores at P < 0.05. RESULTS: The mean age of study participants was
      36.7 +/- 13.8 years. The majority 139 (89.1%) of the study participants ranked
      ''clinician's procedure should be as painless as possible'' as the most important
      clinician determined criteria of a good dental practice while 31 (19.9%) of them
      ranked hotlines available for emergencies as the least. The majority 133 (85.2%)
      of the study participants ranked ''sterile procedure and proper handling of
      equipment'' as the most important patient determined criteria of a good dental
      practice while 30 (19.2%) of them ranked patients being attended by just one
      clinician as the least. There was a statistically significant difference between
      mean scores of clinicians' criteria and patients' criteria ( P = 0.00001),
      participants ranked more patients' criteria than clinicians' criteria.
      CONCLUSION: In determining the criteria for a good dental practice, clinicians'
      perspective as well as patients' perspective should be considered.

PMID- 23974744
TI  - Effectiveness of data collection and information transmission process for disease
      notification in Anambra State, Nigeria.
AB  - BACKGROUND: Disease surveillance and notification (DSN) has been shown to be weak
      in Nigeria, thus, its inability to promptly detect and control epidemics.
      OBJECTIVE: To examine the completeness and timeliness of data collection and
      information transmission process for DSN in the Anambra state. MATERIALS AND
      METHODS: The study was of cross-sectional design and employed the multistage
      sampling method to select 270 health workers who are involved in DSN in Anambra
      state. Data were collected by a mix method of interviewer administered
      questionnaire and observational checklist preceded by key informant interviews
      and desk review. RESULTS: One hundred (43.9%) health workers reported regular
      supply of Integrated Disease Surveillance and Response (IDSR) forms, 25% and
      16.2% reported it was irregular and usually out of stock, respectively. Most
      facilities (81.5%) returned completed forms monthly. Secondary health facilities
      were less likely to submit completed forms, while majority of primary health
      facilities submitted theirs monthly ( X 2 = 4.42, P = 0.035). With respect to
      correctness of records, Health Management Information System records (55.6%) were
      the least correct, while out-patient register (88.9%) was the most correct. Only
      10.0% of health facilities submitted completed forms 5 days after completion,
      88.9% of them submitted completed IDSR002 forms within 2 days of completion,
      while the remainder was submitted 4 days later. CONCLUSION: The health workers
      were not operating the DSN system in the State to optimal functionality.
      Recommendations were therefore made for the periodic training-retraining of
      health personnel on DSN, improved funding, provision of logistics, improved
      supervision, and feedback of information.

PMID- 23974745
TI  - Pregnancy outcome and factors affecting vaginal delivery of twins at University
      of Nigeria Teaching Hospital, Enugu.
AB  - OBJECTIVE: The study aims to determine the differences in maternal and perinatal
      outcomes between caesarean and vaginal deliveries and the factors affecting
      vaginal delivery in twin pregnancy. MATERIALS AND METHODS: An observational study
      to audit twin pregnancies delivered at the University of Nigeria Teaching
      Hospital between 2002 and 2008. Clinical observations were entered into a
      questionnaire immediately after the delivery of the women and the mothers and
      their babies were followed up until the end of the puerperium. RESULTS: There
      were 5298 deliveries within the study period, out of which 117 were twin
      deliveries. This gives a twinning rate of 22 per 1000 deliveries. The mean age of
      the mothers was 30 +/- 5.9 years. Twenty-five (21.4%) women were admitted into
      the hospital for preterm labor. The average gestational age of admission was 32
      +/- 5.8 weeks and the average duration of hospital stay for preterm labor was
      12.6 +/- 9.1 days. Other pregnancy complications observed were severe
      hypertension (14.5%, anemia (9.4%), postpartum hemorrhage (8.5%), puerperal fever
      (5.1%), abruptio placentae, and diabetic mellitus (2.7%). Fifty-nine women
      (50.4%) had vaginal deliveries, 5 (4.3%) had vaginal delivery of the leading twin
      and caesarean delivery of the retained second twin while 53 women (45.3%) were
      delivered by caesarean section. Forty-eight (41%) women had preterm delivery.
      Vaginal deliveries were more common than caesarean section among patients that
      were unbooked than booked P = 0.047 (OR 2.26, 95%CI:0.93-5.53) and those that had
      cephalic presentation of the leading twin, P = 0.0002 (OR = 4.7 95% CI:2.6-8.2).
      Vaginal delivery tended toward statistical significance when the fetal weight of
      the leading twin was 1.5 to 2.5 kg, P = 0.09. The commonest indications for
      caesarean section were abnormal lies and presentations and hypertension in
      pregnancy.Two-hundred and seventeen (92.7%) out of a total of 234 fetuses that
      were delivered in this study were live births and 17 (7.3%) still births. The
      rate of new born admissions in twin 1 was however higher in those delivered by
      Caesarean section (39.6%) than those delivered vaginally (29.7%). Indications for
      admissions into the special baby care units were; prematurity 33 (40.2%), birth
      asphyxia 15 (18.3%), low birth weight 12 (14.6%), neonatal jaundice 10 (12.2%),
      and twin-twin transfusion 4 (4.9%). There was a higher rate of early neonatal
      death in both vaginally delivered twin 1 (9.4%) and twin 2 (11.9%) than those
      delivered by Caesarean section, 3.8 and 3.5%, respectively. CONCLUSION: Cephalic
      presentation of the leading twin, birth weight less than 2.5 kg, and unbooked
      women presenting in advanced labor predisposed to vaginal delivery in twin
      pregnancies. There was however increased risk of still birth and early neonatal
      deaths especially for the leading twin in vaginal deliveries in unbooked women.

PMID- 23974746
TI  - Dry socket following surgical removal of impacted third molar in an Iranian
      population: incidence and risk factors.
AB  - INTRODUCTION: Dry socket (DS) is the most common post-surgical complication
      following extraction of impacted molar teeth. Various risk factors have been
      mentioned for this complication including gender, age, amount of trauma during
      extraction, difficulty of surgery, inappropriate irrigation, infection, smoking,
      and oral contraceptive use. The aim of the current study was to evaluate the
      incidence of DS among surgical removal of impacted third mandibular molar in an
      Iranian Oral and Maxillofacial Clinic and also identifying the background risk
      factors. MATERIALS AND METHODS: A total of 189 patients with a total of 256
      surgeries entered this study. Surgeries to remove impacted third mandibular molar
      teeth between April 2009 and August 2010 were included in this study. A
      questionnaire containing two sections was designed; in the first section
      demographic data along with smoking status, oral contraceptive use, menstrual
      cycle phase, systemic disorders, and use of antibiotics prior to surgery
      collected; in the second section data regarding difficulty of surgery according
      to radiograph and surgeon perception after surgery, length of surgery, and number
      of anesthetic carpules along with data regarding cases returning with DS
      recorded. Data were reported descriptively and analyzed with Fisher's exact test
      and Chi-square with the confidence interval of 95%. RESULTS: The incidence of DS
      was 19.14%. Age, gender, systemic disorder, and antibiotics use prior to surgery
      revealed no significant associations with DS ( P > 0.05). However, incidence of
      DS was significantly relevant to smoking, oral contraceptive use, menstruation
      cycle, difficulty of the surgery according to pre-surgery radiograph evaluation
      and perception of surgeon post-surgery, length of surgery, and number of carpules
      used to reach anesthesia ( P < 0.05). CONCLUSION: It is recommended to identify
      high risk groups when performing extraction surgeries to consider measures in
      order to reduce postoperative complications.

PMID- 23974747
TI  - Weekend versus weekday hospital deaths: analysis of in-patient data in a Nigerian
      tertiary healthcare center.
AB  - AIM: This study aims at comparing weekday deaths to weekend deaths of in-patients
      of a tertiary hospital in Nigeria. MATERIALS AND METHODS: This is a 10-year
      retrospective survey conducted at the Nnamdi Azikiwe University Teaching Hospital
      in which the death records of the hospital were accessed from the various wards
      and health records department to extract relevant data pertaining to the time of
      hospital death. Tests of statistical significance were done using Chi-square test
      at 95% confidence intervals. RESULTS: A total of 3934 deaths were recorded during
      the period of study. The ages ranged from a few hours to 94 years with a mean age
      of 38.5 years. The male to female ratio was 1.2:1. An average of 547 weekend
      deaths and 568 weekday deaths were recorded, giving a ratio of 0.96:1. A ratio of
      weekend to weekday death rate of 0.99:1 and 0.93:1 for the males and females,
      respectively was noted. The labor ward, followed by the intensive care unit (ICU)
      had the highest weekend to weekday death ratio of 1.72:1 ( P = 0.0461) and 1.41:1
      ( P = 0.1440), respectively. Weekend deaths were less in the other wards, with
      the gynaecological ward having the least ratio of 0.63:1 ( P = 0.7360).
      CONCLUSION: The rate of hospital deaths was generally found not to vary
      significantly over the weekends and weekdays in the hospital except for the labor
      ward which had significantly higher weekend to weekday death rates of 1.72:1.
      There is therefore need for confidential enquiry into the causes of hospital
      deaths, especially in the labor ward, in order to identify and prevent avoidable
      deaths.

PMID- 23974748
TI  - Pattern of cancer deaths in the medical wards of a teaching hospital in South
      East Nigeria.
AB  - BACKGROUND: Cancers are emerging public health problems in developing countries
      like Nigeria. The epidemiological shift and aging population make cancers a
      challenge. OBJECTIVE: We set out to describe the pattern of death due to cancer
      in our medical ward. The hospital is one of the premier hospitals covering the
      South East zone of Nigeria. MATERIALS AND METHODS: We retrospectively reviewed
      the case notes and death certificates of all who died of cancer in our adult
      medical wards for 16 years (January 1995 to December 2010). STATISTICAL ANALYSIS
      USED: Statistical Package for Social Sciences (SPSS Inc. Chicago, IL) version
      17.0 was used. RESULTS: Twenty seven thousand, five hundred and fourteen patients
      were admitted into the medical wards. Six thousand, two hundred and fifty died.
      Out of the 6250 deaths, cancers accounted for 7.6%. Male to Female ratio was
      2.4:1. The mean age at death was 43.7 +/- 17.4 years. The mean age at death in
      both sexes was similar (42.9 +/- 17.5 for men and 45.7 +/- 17.0 years for women),
      P = 0.109. Primary liver cell carcinoma was the most common cause of death among
      men (40.8%), while cancer of hematopoietic organ was the most common in women
      (48.7%). The overall fatality rate was 1.7% (477/27 514) of medical admissions.
      Younger and middle age groups were most commonly affected in both sexes.
      CONCLUSION: Since the most productive age groups were affected, governments in
      developing countries should as a matter of urgency put in place adequate cancer
      preventive and curative services.

PMID- 23974749
TI  - Clustering of cardiovascular disease risk-factors in semi-urban population in
      Northern Nigeria.
AB  - INTRODUCTION: Non-communicable diseases (NCDs) are major causes of morbidity and
      mortality particularly for developing countries. Large proportion of all NCDs
      deaths are occurring in low- and -middle-income countries are estimated to occur
      in people under 70-years-old. These low- and middle-income are undergoing
      epidemiological transition which allows the concomitant occurrence of both
      communicable and NCDs due to adoption of western life-style that predisposes them
      to development of these diseases. It is also known that there are risk-factors
      that tend to cluster in individuals and make them more susceptible to NCDs
      especially cardiovascular diseases (CVDs). Among NCDs, CVDs constitute the
      largest share responsible for 48% of all deaths due to NCDs. To determine extend
      of clustering of these risk-factors in a semi-urban community in northern
      Nigeria, a population-based study was carried out. MATERIALS AND METHODS: This
      study was conducted in Dakace, a semi-urban settlement near Zaria. A simple
      random sampling of 199 eligible respondents out of 424 was adopted to select
      study participants. An interviewer-administered questionnaire was used to collect
      socio-demographic information, smoking habits, alcohol consumption as well as
      level of physical activity. The following measurements were carried out on these
      respondents: Blood pressure (BP), fasting blood glucose, serum lipids, weight,
      and height to calculate body mass index (BMI). RESULTS: There were of 199
      participants: 94 males (47.2%) and 105 females (52.8%) with an overall mean age
      of 39.9 +/- 15.6 years. About 20% had no risk factor; more females than males had
      risk-factors. Proportion of subjects with risk-factors increase with increasing
      BMI, particularly high BP; physical activity does not protect subjects from
      developing risk-factors. CONCLUSION: This study clearly shows that CVD risk
      factors are prevalent even in segment of the population that hitherto may be
      considered free and the prevalence of these risk-factors are high compared to
      some obtained from other part of Nigeria.

PMID- 23974750
TI  - The relationship between vertical cup-disc ratio and body mass index in Port
      Harcourt, Nigeria.
AB  - BACKGROUND: Glaucoma is the leading cause of irreversible blindness in the world
      and risk factors to developing glaucoma must be determined early to prevent
      blindness from the disease. AIM: To determine the relationship between vertical
      cup disc ratio (VCDR) and body mass index (BMI) in a population screened for
      glaucoma in Port Harcourt, Nigeria. MATERIALS AND METHOD: This study was part of
      a one-day screening exercise for glaucoma at the University of Port Harcourt.
      Demographic data included age, sex, race and occupation. Height was measured with
      a wall-mounted tape and weight with a bathroom scale. Intraocular pressure was
      measured with Perkins applanation tonometer and funduscopy was with direct
      ophthalmoscope. BMI was calculated as weight in kilograms divided by the square
      of height in meters (Weight/Height2). RESULTS: A total of 491 subjects were
      screened; consisting of 230 males (46.8%) and 261 females (53.2%). The mean age
      was 35+/-13.29 years. About 28%(n=141) of the participants were overweight while
      17.7%(n=87) were obese. The mean BMI was 25.39 +/- 4.82 kg/m 2 and the mean VCDR
      for both eyes was 0.38+/-0.13mmHgratios have no units. Most participants (n=864;
      89.4%) had normal VCDR. Only 102 (10.6%) had cupped discs. There was no
      statistically significant relationship between BMI and VCDR (P= 0.947; R2 =
      0.01). CONCLUSION: Obesity was not associated with a larger VCDR.

PMID- 23974751
TI  - Pediatric HIV in Kano, Nigeria.
AB  - BACKGROUND: Pediatric human immunodeficiency virus (HIV) infection is still an
      important public health issue despite a decrease in global, national, and local
      seroprevalence rates. DESIGN: A prospective, hospital-based study was conducted.
      MATERIALS AND METHODS: One-hundred and sixty children presenting for the first
      time to the hospital were studied. Each child had a detailed physical examination
      and initial double rapid HIV antibody tests. A virological confirmatory test was
      done for those aged less than 18 months of age with positive results. Mothers of
      HIV-infected children also had HIV testing. HIV-infected children were enrolled
      into HIV care and followed up for 6 months. Data were analyzed using the SPSS
      16.0 for Windows. RESULTS: Twenty-two (13.8%) children were confirmed HIV
      infected. The mean age was 26.9 +/- 30.8 months. Male to female ratio was 1.1:1.
      Probable modes of transmission were mother-to-child in 63.6%, group circumcision
      in 22.7%, sexual transmission in 9.1% and unscreened blood transfusion in 4.5%.
      The most frequent symptoms on presentation were fever in 95.4% of patients, cough
      and weight loss in 77.3% and diarrhoea in 59.1%. The most common signs were
      hepatomegaly in 77.3%, pyrexia and crepitations in 72.7%, and pallor in 40.9%.
      Commonly diagnosed conditions were undernutrition, diarrheal disease, oral
      thrush, and pneumonia. Tuberculosis co-infection was diagnosed in 18.2% of
      children. Fourteen (63.6%) children had advanced and severe immunodeficiency.
      Mortality rate over 6 months was 18.2%. CONCLUSION: Early diagnosis of pediatric
      HIV and prompt institution of treatment in children would go a long way in
      reducing the scourge of the disease.

PMID- 23974752
TI  - The histopathological pattern of liver biopsies at the University of Benin
      Teaching Hospital.
AB  - OBJECTIVE: Microscopic examination of liver tissues remains an essential part in
      the diagnostic work-up of patients with liver diseases. The aim of this study is
      to determine the histopathological pattern of liver diseases at the University of
      Benin Teaching Hospital, Benin City, Nigeria. MATERIALS AND METHODS: This is a
      retrospective study of all cases of liver biopsies between January 2005 and
      December 2011. The appropriate data was obtained from the Surgical day book of
      the department of histopathology. The data was analyzed to reflect age, sex, and
      pathological diagnosis of the lesions. RESULTS: A total of 80 cases of liver
      biopsies were reported during the 7-year period. There were 50 males and 30
      females with a male:female ratio of 1.7:1. The age ranged from 4 months to 69
      years with a mean age of 38.4 +/- 13.3 years. The highest incidence was in the 4
      th decade. The three common histopathological diagnoses were inflammatory
      lesions, 63.8%; malignant neoplasms, 22.5%, and liver cirrhosis in 6.3% of cases.
      Other less common lesions were alcoholic liver disease and steatosis. This peak
      age incidence of chronic hepatitis precedes that of hepatocellular carcinoma by
      about two decades. CONCLUSION: The preponderance of chronic hepatitis,
      hepatocellular carcinoma, and liver cirrhosis in this study is similar to those
      already established in the African literature, with hepatitis B and/or C being
      the most incriminated risk factors due to their endemicity in our environment.
      Public enlightenment programs, widespread implementation of hepatitis B virus
      vaccination, and surveillance of individual at-risk are essential for the control
      of hepatitis infection and its late complications.

PMID- 23974753
TI  - Hepatic transaminase and alkaline phosphatase enzyme levels in HIV/HBV co
      infected and HIV mono-infected patients in Maiduguri, Nigeria.
AB  - BACKGROUND: Studies have shown that HIV-HBV co-infected patients have an
      increased risk of liver-related morbidity and mortality compared to their HIV
      mono-infected counterparts. Furthermore, it has been reported that HIV-HBV co
      infected patients have a significantly high incidence of drug-induced
      hepatotoxicity following commencement of HAART than HIV-mono-infected patients.
      OBJECTIVES: To compare the levels of aspartate amino transferase (AST), alanine
      amino transferase (ALT) and alkaline phosphatase (ALKPO 4 ) enzyme levels between
      HAART naive HIV-HBV co-infected patients and their HIV-mono-infected
      counterparts. MATERIALS AND METHODS: A cross-sectional descriptive study in which
      142 newly diagnosed HIV/HBV co-infected and HIV mono-infected adults were
      investigated for alkaline aminotransferase, aspartate aminotransferase and
      alkaline phosphatase enzyme levels. RESULTS: The study subjects comprised of 80
      (56.3%) females and 62 (46.7%) males. The age range of the study population was
      15-65 years. The mean ages of male and female subjects were 45.5 +/- 10.5 years
      and 39.1 +/- 7.5 years respectively ( P < 0.05). Sixty-three (44.4%) study
      subjects were HIV/HBV co-infected while 79 (55.6%) were HIV mono-infected. The
      mean ALT enzyme level of HIV/HBV co-infected subjects was significantly higher
      than that of HIV mono-infected ones i.e., 42.12 IU/l vs. 27.86 IU/l, ( P =
      0.038). However, there was no statistically significant difference in the mean
      AST (30.14 IU/l vs. 29.09 IU/l, P = 0.893) and ALKPO 4 (55.86 IU/l vs. 60.97
      IU/l, P = 0.205) enzyme levels between HIV-HBV co-infected and HIV mono-infected
      subjects albeit the two enzymes were moderately elevated in both categories of
      subjects. CONCLUSION: The significantly elevated ALT enzyme levels amongst HIV
      HBV co-infected subjects suggest that HIV-HBV co-infected patients may have an
      increased risk of liver-related morbidity and mortality than their HIV mono
      infected counterparts. Screening for serological markers of chronic HBV
      infection, as well as hepatic transaminase enzyme levels in all newly diagnosed
      HIV-positive patients is therefore recommended before commencement of HAART.

PMID- 23974754
TI  - A 20 year retrospective analysis of medicolegal deaths in a tertiary hospital
      setting in Nigeria.
AB  - OBJECTIVE: To determine and classify the various types of medicolegal deaths as
      seen at University of Benin Teaching Hospital (UBTH), Benin City, Nigeria.
      MATERIALS AND METHODS: This is a retrospective study of all the medicolegal
      deaths seen in the Department of Histopathology, (UBTH, Benin City over a 20 year
      period (January 1990-December 2009) as recorded in the autopsy registers of the
      department. RESULT: A total of 5035 autopsies were done during the period, 89% of
      which were coroner cases. Four thousand, four hundred and eighty-one coroner
      cases representing 12.5% of all bodies received by the mortuary during the period
      were studied. The male to female ratio was 1.9:1, with an overall mean age of
      38.3 years. The ages ranged from 1 day to 101 years with a peak incidence in the
      25-44 years age group. A total of 553 children and 3928 adults were involved. The
      commonest indication for coroner's autopsy was sudden unexpected natural deaths
      (SUNDs) which accounted for 65.5% of the cases. Other causes of death were
      accidents, homicide, suicide, and undetermined causes representing 28.6, 5.0,
      0.5, and 0.4%, respectively. Commonest cause of SUND was cardiovascular diseases
      with complications of hypertension being the most common CVS disease (26.9%).
      Road traffic accident was the commonest form of accident causing death (88.7%).
      Public enlightenment and health education about routine medical screening will
      help to reduce causes of natural deaths. CONCLUSION: This study shows the pattern
      of medicolegal autopsies in UBTH and this preliminary data will provide a
      baseline for future research and help in formulating policies to help in
      reduction of preventable causes of death.

PMID- 23974755
TI  - Metallic sewing needle ingestion presenting as acute abdomen.
AB  - We reported an unusual case of a 26-year-old man presenting to surgical emergency
      as generalized peritonitis following an ingestion of multiple metallic sewing
      needles. The X-ray of his abdomen showed pneumoperitoneum and multiple metallic
      foreign bodies in the abdominal cavity. An ultrasonogram of his abdomen showed
      multiple metallic foreign bodies in the abdominal cavity and urinary bladder.
      Emergency exploratory laparotomy was performed. On laparotomy, gastric and
      duodenal perforation was found through which metallic sewing needles were
      protruding out. A peritoneal lavage was done, and all the sewing needles were
      extracted from the perforation site, paracolic gutter, liver parenchyma, and
      urinary bladder. The primary repair of the perforation with omental patching was
      done with the drainage of subhepatic space and pelvic cavity. These multiple
      ingested sewing needles led to the perforation of the stomach and the duodenum,
      which resulted in perforation peritonitis. 

PMID- 23974756
TI  - CT-guided percutaneous transthoracic lung biopsy: first experience in Ibadan,
      Nigeria.
AB  - Percutaneous lung biopsy had been described in the nineteenth century by Leyden,
      but image- guided needle chest biopsy only gained widespread acceptance in the
      1970s. Currently, tissue sampling of a thoracic lesion is indicated when the
      diagnosis cannot be obtained by the non-invasive techniques and cytological
      diagnosis will modify the stage of the disease or influence the therapeutic
      strategy. Cytology obtained by small-gauge needle aspiration biopsy confirms the
      nature of the lesion in 80 - 95% of cases and carry a low incidence of major
      complications. The purpose of this report was to provide information on our first
      experience with CT-guided biopsy and show that with some innovativeness much can
      be achieve with limited resources and good team work. We performed a CT of the
      thorax using appropriately placed improvised metal markers, which determined the
      optimal cutaneous entry point. We then re-checked the location of the lesion
      scanning intermittently at 5mm slice thickness; we marked the entry point with a
      pen and cleaned the surface with methylated spirit. A local anaesthetic was
      subcutaneously injected around marked area. We used a 21G aspiration needle to
      obtain cytology sample then 18G Trucut biopsy needle to obtain histology
      specimen. The length of the needle was chosen based on predetermined distance of
      the target lesion from the skin estimated from the CT images. Our patient was a
      51-year-old Nigerian female with a peripherally located nodule in the posterior
      aspect of the right lung. She had CT-guided biopsy of the nodule. The procedure
      was well tolerated with no complication of pneumothorax. The histology report
      provided the basis for treatment regimen. Our experience indicates that
      percutaneous transthoracic CT-guided needle biopsy is feasible and a safe
      procedure in our hospital for evaluation of undetermined lung lesions. 

PMID- 23974757
TI  - Takayasu arteritis in young male.
AB  - Hypertension is one of the common diseases affecting general population. The
      World Health Organization has concluded that hypertension is the major factor
      responsible for the most deaths worldwide, 12.8% per year or more than seven
      million. Additionally hypertension is rated third on the list of factors
      responsible for the burden of disease during life, as measured by disability
      adjusted life-years. The study, diagnosis and treatment of hypertension in the
      young constitute one of the major health challenges today, because of high
      percentage of potentially curable chance if the cause could be found. Indeed
      intensive study and investigations are required to unravel the underlying cause.
      Here we present a case of typical Takayasu arteritis presented with swelling in
      the right neck and hypertension. 

PMID- 23974758
TI  - Mesenteric lipoma causing recurrent intestinal obstruction.
AB  - Although lipoma is a common tumor found in almost all parts of the body, that
      occurring in the mesentery of the gut is a rarity. A 29-year-old man presented in
      our center with a 10-year history of recurrent central colicky abdominal pain,
      vomiting, constipation, and central abdominal mass. Exploratory laparotomy
      revealed a huge smooth yellow mass in the mesentery of the mid ileum. Resection
      of the affected segment of the ileum and end to end ileal anastomosis were
      carried out. Histology report confirmed lipoma. He had uneventful post-operative
      recovery. Mesenteric lipoma should be considered as a possible differential
      diagnosis in a patient with recurrent features of intestinal obstruction and a
      mobile abdominal mass. A high index of suspicion and improvement on the pre
      operative diagnosis and treatment are needed in secondary health facilities in
      Africa. 

PMID- 23974760
TI  - Sacrohysteropexy with synthetic mesh in Aba, South-Eastern Nigeria: a report of
      three cases and review of the literature.
AB  - The surgical treatment of uterovaginal prolapse in women who wish to preserve
      their uteri for fertility presents a challenge to a gynecologist. This is
      particularly more challenging in Nigeria and the rest of Africa where there is
      not only a strong cultural aversion to hysterectomy but women also prefer large
      family size and male babies. This underscores the need for fertility friendly,
      uterus-preserving procedures. Three young women under the age of 40 presented
      with uterovaginal prolapse. They were of low parity and wanted to preserve their
      uteri for future reproductive function. They had open abdominal suspension of
      their uteri to the sacrum using a synthetic polypropylene mesh. A pus-string
      suture was also used to obliterate their pouch of Douglas to prevent future
      enterocele. Pelvic anatomy was restored and normal vaginal axis was achieved.
      They had uneventful post-operative period. In resource-limited settings, open
      abdominal (rather than laparoscopic) sacrohysteropexy with synthetic mesh is an
      effective and safe alternative to Manchester operation and other vaginal
      procedures in women who desire to preserve the uterus for future reproductive
      function. 

PMID- 23974761
TI  - Physician heal thyself.

PMID- 23974762
TI  - Obesity IS a disease!

PMID- 23974763
TI  - Healthy obese persons: how can they be identified and do metabolic profiles
      stratify risk?
AB  - PURPOSE OF REVIEW: New research supports the intuitive observation that many
      persons classified as obese are healthy, and should not be treated and
      categorized medically as diseased. There is increasing agreement that major blood
      biomarkers are often not discriminatory, as for example, the return to normal
      blood glucose levels in bariatric patients who do not have long-term benefits.
      Although weight loss is appreciated to improve metabolic and inflammatory
      parameters, the cellular and immune factors that couple obesity to
      cardiometabolic risk are only partially understood. RECENT FINDINGS: Reduced BMI
      upon successful bariatric surgery does not always result in reduced pericardial
      fat; certain patients gain ectopic fat, which should be considered an adverse
      response. There is emerging evidence that pericardial fat volume and brown fat
      stores may provide individualized patient assessments. SUMMARY: Some obese
      persons can be relieved of the additional stigma of classification in a major
      disease category, and unnecessary medical interventions and costs can be reduced.
      Other patients should be monitored more closely for unexpected adverse outcomes.

PMID- 23974765
TI  - Lifestyle medicine: the future of chronic disease management.
AB  - PURPOSE OF REVIEW: Lifestyle medicine is a new discipline that has recently
      emerged as a systematized approach for management of chronic disease. The
      practice of lifestyle medicine requires skills and competency in addressing
      multiple health risk behaviours and improving self-management. Targets include
      diet, physical activity, behaviour change, body weight control, treatment plan
      adherence, stress and coping, spirituality, mind body techniques, tobacco and
      substance abuse. This review focuses on the impact of a healthy lifestyle on
      chronic disease, the rarity of good health and the challenges of implementing a
      lifestyle medicine programme. RECENT FINDINGS: Unhealthy lifestyle behaviours are
      at the root of the global burden of noncommunicable diseases and account for
      about 63% of all deaths. Over the past several years, there has been an increased
      interest in evaluating the benefit of adhering to 'low-risk lifestyle' behaviours
      and ideal 'cardiovascular health metrics'. Although a healthy lifestyle has
      repeatedly been shown to improve mortality, the population prevalence of healthy
      living remains low. SUMMARY: Lifestyle medicine presents a new and challenging
      approach to address the prevention and treatment of noncommunicable diseases, the
      most important and prevalent causes for increased morbidity and mortality
      worldwide.

PMID- 23974766
TI  - Childhood obesity in America.
AB  - PURPOSE OF REVIEW: To provide an overview of the current advances in childhood
      obesity physiology, intervention, and prevention. RECENT FINDINGS: Structural and
      functional brain impairments are present in obese adolescents with metabolic
      syndrome (MetS). Aerobic training for 20 or 40 min per day produced similar
      affects on metabolic risk factors. Vitamin D supplementation has been shown to
      improve the metabolic risk factors in obese children; however, obese children
      require greater doses to treat vitamin D deficiency. A 10-week community-based
      exergaming weight management program significantly decreased the BMI in obese
      children. SUMMARY: There is surmounting research on MetS and its associated risk
      factors in obese children. Gaining a comprehensive overview of the factors
      associated with obesity in children is crucial in developing the most effective
      intervention strategies. Community-based and family-centered interventions have
      generated positive results in reducing children's BMI and improving MetS risk
      factors. In addition to obesity intervention efforts, ongoing prevention
      initiatives are imperative to reduce the prevalence of childhood obesity.

PMID- 23974764
TI  - A complications-based clinical staging of obesity to guide treatment modality and
      intensity.
AB  - PURPOSE OF REVIEW: The current medical model for obesity management is BMI
      centric because BMI is the predominant measure used to gauge disease severity, as
      well as indications for various treatment modalities. Recent advancements in
      therapy and understanding of the relationship between BMI and obesity-related
      complications call for a re-examination of this approach. RECENT FINDINGS:
      Advancements in treatment, including the recent approval of two new weight loss
      medications in the USA, have enabled development of new medical models for
      management of obesity. On the basis of accumulating data demonstrating the
      benefits of weight loss regarding multiple obesity-related complications (e.g.,
      diabetes prevention, type 2 diabetes mellitus, cardiovascular disease risk,
      nonalcoholic steatohepatitis, sleep apnea), a complications-centric model is
      proposed that employs weight loss as a tool to treat and prevent obesity
      comorbidities. This model assures that the aggressiveness of therapy is
      commensurate with disease severity, and that therapy is directed at those obese
      patients who will benefit most from weight loss therapy. The treatment algorithm
      is comprehensive in addressing complications and quantitative when possible in
      the staging of risk or disease severity. SUMMARY: A complications-centric
      approach to obesity management identifies patients who will benefit most from
      weight loss, and optimizes patient outcomes, benefit/risk ratio, and the cost
      effectiveness of interventions.

PMID- 23974767
TI  - The sugar-sweetened beverage wars: public health and the role of the beverage
      industry.
AB  - PURPOSE OF REVIEW: To discuss the current data on sugar-sweetened beverage (SSB)
      consumption trends, evidence of the health impact, and the role of industry in
      efforts to reduce the consumption. RECENT FINDINGS: Previously rising SSB
      consumption rates have declined recently, but continue to contribute added sugars
      beyond the limit advised by the American Heart Association. A recent meta
      analysis concluded that SSBs likely increase body weight and recent long-term
      studies support the previous findings of increased risk of diabetes,
      dyslipidemia, and hypertension. Beverage companies have played an active role in
      some SSB reduction efforts by reducing the sale of SSBs in schools, limiting
      television advertising to children, and increasing the availability of smaller
      portion-size options. Industry has opposed efforts to restrict the availability
      of large portion sizes and implement an excise tax. Current industry efforts
      include the promotion of alternative beverages perceived to be healthier as well
      as SSBs through Internet and social media. SUMMARY: Continuing high SSB
      consumption and associated health risks highlight the need for further public
      health action. The beverage industry has supported some efforts to reduce the
      consumption of full sugar beverages, but has actively opposed others. The impact
      of industry efforts to promote beverage alternatives perceived as healthier is
      unknown.

PMID- 23974768
TI  - New medications for obesity management: changing the landscape of obesity
      treatment.
AB  - PURPOSE OF REVIEW: Despite being one of the most prevalent chronic diseases,
      obesity was not recognized as such until very recently. Although linked to
      ubiquitous diseases like diabetes, hypertension, coronary artery disease,
      obstructive sleep apnea, and many others, targeted treatments are few. Diet,
      exercise, and behavior modification are the pillars of weight loss. When they
      alone do not achieve the required weight reduction, medications may be used for
      patients with a BMI above 30 or above 27 if obesity-related comorbidities are
      present. The spectrum of pharmacologic agents aimed at obesity treatment will be
      reviewed. RECENT FINDINGS: Two medications, phentermine and orlistat, have been
      the only agents approved many years ago and now still standing. Others have come
      and gone, removed from the market by the Food and Drug Administration (FDA)
      because of harmful side-effects. However, in the last few years, new drugs have
      started to emerge. Since 2012, two new medications phentermine-topiramate
      extended-release combination and lorcaserin have been FDA approved, while at
      least one more, naltrexone SR/bupropion SR combination is expected to be re
      evaluated by the FDA in 2014. SUMMARY: Treating obesity is crucial as it will
      ultimately result in the prevention of many related chronic diseases and will
      decrease morbidity and mortality. Weight loss medications are a valuable part of
      the clinician's toolbox in the treatment of obesity and should be used when
      appropriate. Having a variety of medications would be a great asset to
      accommodate various patients' needs and pre-existing medical conditions.

PMID- 23974770
TI  - Duodenal-jejunal bypass liners: outcomes in glycaemic control and weight loss.
AB  - PURPOSE OF REVIEW: Duodenal-jejunal bypass liners (DJBLs) are a novel therapy
      with potential treating a range of metabolic diseases. This review discusses the
      weight loss and glycaemic improvements observed following the use of the DJBL.
      RECENT FINDINGS: We summarize the evidence for the clinical application of DJBL
      to date. Within this, we outline the evidence available on the mechanisms of the
      observed effects. SUMMARY: Based on the most recent trials, we cannot fully mimic
      the clinical or physiological effects of bariatric surgery with this device, but
      we are getting closer.

PMID- 23974771
TI  - What the new obesity guidelines will tell us.
AB  - PURPOSE OF REVIEW: The purpose of the review is to update the reader on the long
      anticipated Obesity 2, the second iteration of 'Clinical Guidelines on the
      Identification, Evaluation, and Treatment of Overweight and Obesity in Adults:
      the Evidence Report'. RECENT FINDINGS: Obesity 2 maintains a focus on primary
      care practitioners and their patients in an effort to reduce cardiovascular risk.
      Just as Obesity 1 limited the literature review to the years 1980-1997, Obesity 2
      limits the literature under consideration from 1999 to 2011. However, because of
      the painstaking methodology employed, the scope of the Obesity 2 is of necessity
      more limited with five critical questions. These deal with risks of overweight
      and obesity, benefits of weight loss and evaluate three treatment areas - diet,
      behavioral therapies and surgical therapies. The critical questions inform
      recommendations in these same areas. SUMMARY: Although not comprehensive in
      scope, the guidance offered in Obesity 2 is backed by stringent approaches to
      limit bias and assuring rigor, thus producing recommendations one can trust in
      the areas covered.

PMID- 23974769
TI  - Sarcopenic obesity: how do we treat it?
AB  - PURPOSE OF REVIEW: The increasing prevalence of sarcopenic obesity in older
      adults has heightened interest in identifying the most effective treatment. This
      review highlights recent progress in the management, with an emphasis on
      lifestyle interventions and pharmacologic therapy aimed at reversing sarcopenic
      obesity. RECENT FINDINGS: Whereas weight loss and exercise independently reverse
      sarcopenic obesity, they act synergistically in combination to improve body
      composition and physical function, beyond which is observed with either
      intervention alone. Optimizing protein intake appears to have beneficial effects
      on net muscle protein accretion in older adults. Myostatin inhibition is
      associated with favorable changes in body composition in animal studies, although
      experience in humans is relatively limited. Testosterone and growth hormone offer
      improvements in body composition, but the benefits must be weighed against
      potential risks of therapy. GHRH-analog therapy shows promise, but further
      studies are needed in older adults. SUMMARY: At present, lifestyle interventions
      incorporating both diet-induced weight loss and regular exercise appear to be the
      optimal treatment for sarcopenic obesity. Maintenance of adequate protein intake
      is also advisable. Ongoing studies will determine whether pharmacologic therapy
      such as myostatin inhibitors or GHRH analogs have a role in the treatment of
      sarcopenic obesity.

PMID- 23974772
TI  - Inherited defects of thyroid hormone-cell-membrane transport: review of recent
      findings.
AB  - PURPOSE OF REVIEW: This review summarizes the most significant findings over the
      last year regarding human and animal models deficient in thyroid hormone cell
      membrane transporters (THCMTs). Although several THCMTs have been modelled in
      genetically engineered mice, the only THCMT defect known in humans is that caused
      by mutations in the monocarboxylate transporter 8 (MCT8) gene. RECENT FINDINGS:
      The importance of several amino acid residues has been assessed in vitro to
      further our understanding on the structure-function of the MCT8. The
      administration of the thyromimetic compound, diiodothyropropionic acid, has been
      tested in patients with MCT8 gene mutations, following studies of its use in
      mice. Another thyroid hormone analogue, 3,3',5,5'-tetraiodothyroacetic acid, was
      tested in Mct8-deficient mice. The phenotypes of L-type aminoacid transporter 2
      and organic anion transporting polypeptide 1C1 deficiencies have been studied in
      mouse models. Mct8/organic anion transporting polypeptide 1C1 double knockout
      mice have been shown to manifest neurodevelopmental deficits. Zebrafish is
      emerging as another vertebrate model that may be useful to study the role of Mct8
      in brain development. SUMMARY: Studies on the pathogenesis and therapy of MCT8
      deficiency are in progress, and new vertebrate models that are suitable to study
      the neurological consequences of the syndrome are being explored.

PMID- 23974773
TI  - Selenium and the thyroid.
AB  - PURPOSE OF REVIEW: To provide information on the role of the essential trace
      element selenium, which enables appropriate thyroid hormone synthesis, secretion,
      and metabolism, and to discuss supplementation with various selenium compounds,
      which prevent thyroid diseases such as goiter and exert beneficial effects in
      thyroid autoimmune diseases. RECENT FINDINGS: Selenium administration in both
      autoimmune thyroiditis (M. Hashimoto) and mild Graves' disease improves clinical
      scores and well-being of patients and reduces autoimmune antibody titres in
      several prospective, placebo-controlled supplementation studies. SUMMARY:
      Adequate nutritional supply of selenium, together with the two other essential
      trace elements iodine and iron, is required for a healthy thyroid during
      development and adolescence, as well as in the adult and aging populations.

PMID- 23974774
TI  - Hypothyroidism in the newborn period.
AB  - PURPOSE OF REVIEW: This review summarizes significant advances in the
      epidemiology, pathophysiology and treatment of congenital hypothyroidism, with a
      focus on thyroid dysfunction in preterm infants. RECENT FINDINGS: Congenital
      hypothyroidism appears to be increasing in incidence, primarily due to increased
      stringency of screening strategies, with smaller contributions from changing
      demographics and improved survival of increasingly premature infants. The
      greatest increase has been in mildly affected infants. Although many such cases
      are transient, some eventually prove to be severe and/or permanent. In preterm
      infants, transient hypothyroidism is common and may be delayed in onset. The
      cause is probably multifactorial, and inadequate iodine intake may contribute to
      some cases. Transient hypothyroxinemia of prematurity, also common in premature
      infants, is correlated with markers of inflammation. Despite concern about the
      potential morbidity of transient hypothyroxinemia of prematurity, the benefits
      and safety of treatment have not been established. Novel genetic causes of
      congenital hypothyroidism continue to be identified, and accumulating data
      support the sensitivity of infants with severe congenital hypothyroidism to small
      changes in levothyroxine formulation. SUMMARY: Changes in newborn screening
      strategies have increasingly identified thyroid function abnormalities of unclear
      clinical significance. Novel causes of congenital hypothyroidism continue to be
      identified, and new data continue to emerge regarding optimal therapy.

PMID- 23974775
TI  - The aging thyroid.
AB  - PURPOSE OF REVIEW: As life expectancy increases and population age advances,
      diagnosis and treatment of diseases common in the geriatric population assume an
      increasingly important role in modern medicine. In the last few years, the
      emergence of age-specific reference ranges for thyroid-stimulating hormone (TSH)
      has added to the complexity of diagnosis of thyroid dysfunction in this age
      group, especially in the 'subclinical' category. RECENT FINDINGS: The recent
      studies confirm an increase in population TSH distribution with age, both in
      cross-sectional and longitudinal studies. Conclusive evidence about adverse
      cardiovascular, metabolic, and cognitive consequences of subclinical
      hypothyroidism in the elderly remains elusive. The transient nature of subtle
      degrees of thyroid dysfunction in a significant proportion of elderly patients
      has also been reproduced in the recent publications. SUMMARY: A growing body of
      literature in the last few years, reviewed here, highlights the importance of
      employing additional caution before assigning diagnoses of hypothyroidism or
      hyperthyroidism to elderly patients and initiation of treatment modalities that
      can have long-lasting effects.

PMID- 23974776
TI  - Combination L-T3 and L-T4 therapy for hypothyroidism.
AB  - PURPOSE OF REVIEW: Because of the longstanding controversy regarding whether
      hypothyroid patients can be optimally replaced by treatment with levothyroxine (L
      T4) alone, numerous studies have addressed potential benefits of combined therapy
      of triiodothyronine (T3) with L-T4. Results of these studies have failed to
      support a potential benefit of combined therapy. A strong argument for the
      addition of L-T3 to L-T4 monotherapy has been lacking until recent genetic
      studies indicated a rationale for such therapy among a small fraction of the
      hypothyroid patient population. RECENT FINDINGS: Interest in this issue has
      focused on the importance of the deiodinases in maintaining the euthyroid state
      and the role of genetic polymorphisms in the deiodinase genes that would affect
      thyroid hormone concentrations in both blood and tissues. One such polymorphism
      in the D2 gene, Thr92Ala, is associated with reduced T4 to T3 activation in
      skeletal muscle and thyroid, linked to obesity and alterations in thyroid
      pituitary feedback, and in responses to thyroid hormone treatment. SUMMARY:
      Although our professional organizations continue to recommend L-T4 alone for the
      treatment of hypothyroidism, the possibility of a D2 gene polymorphism should be
      considered in patients on L-T4 monotherapy who continue to complain of fatigue in
      spite of dosage achieving low normal serum thyroid stimulating hormone levels. A
      suggestive clue to the presence of this polymorphism could be a higher than
      normal free T4/free T3 ratio. Clinicians could consider adding T3 as a
      therapeutic trial in selected patients. Future well controlled clinical trials
      will be required to more fully resolve the controversy.

PMID- 23974777
TI  - When thyroid hormone replacement is ineffective?
AB  - PURPOSE OF REVIEW: In this article, we will consider the failure of thyroid
      hormone replacement therapy to normalize serum thyroid stimulating hormone
      concentrations. We will review circumstances and causes for failures, discuss
      pertinent unpublished personal cases of didactical value, and provide practical
      suggestions for providers encountering patients with similar presentations.
      RECENT FINDINGS: Recent data are available on the benefit of novel formulations
      of levothyroxine therapy on malabsorption. SUMMARY: Most frequently, reasons for
      ineffectiveness are noncompliance, inappropriate administration of levothyroxine,
      gastrointestinal disorders, and drug interactions. The diagnostic work-up should
      include careful history to elucidate the potential reasons for the ineffective
      therapy.

PMID- 23974778
TI  - Nonthyroidal illness syndrome.
AB  - PURPOSE OF REVIEW: The current state of the pathophysiology, diagnosis, and
      therapeutic implications of the nonthyroidal illness syndrome is reviewed. RECENT
      FINDINGS: Previous studies attributed the development of the nonthyroidal illness
      syndrome to alterations in three main areas of thyroid hormone metabolism:
      deiodinase activity, thyroid-stimulating hormone secretion, and hormone binding
      to serum proteins. New studies suggest that alterations in thyroid hormone
      transport into tissues and alterations of the nuclear thyroid hormone receptors
      may also play a role. Therapy of the nonthyroidal illness syndrome remains a
      controversial topic. SUMMARY: Multiple factors lead to the development of the
      nonthyroidal illness syndrome, including alterations in type 1 and 3 deiodinase
      activity, thyrotropin-releasing hormone and thyroid-stimulating hormone
      secretion, hormone binding to plasma proteins, thyroid hormone transporter
      expression and activity, and the thyroid hormone nuclear receptor complex. These
      data show that acute and chronic illness affect all aspects of thyroid hormone
      metabolism and action. Some of these changes are physiologic and some are
      pharmacologic. The mediators of these alterations are still largely unclear.
      There continues to be no indication for thyroid hormone therapy in the vast
      majority of patients with the nonthyroidal illness syndrome, although interesting
      data suggest a possible role for treating a small subset of patients.

PMID- 23974779
TI  - Diabetes, antihyperglycemic medications and cancer risk: smoke or fire?
AB  - OBJECTIVE: The aim of this review article is to discuss the epidemiological links
      between diabetes and cancer; the potential biological mechanisms linking
      diabetes, obesity and cancer; the risk of cancer associated with antidiabetic
      medications. METHODS: The data discussed in this review were obtained from the
      American Association of Clinical Endocrinologists Consensus Conference on
      Diabetes and Cancer, held in New York, NY, USA, September 2012. RESULTS: The
      results of these studies demonstrate a significant association between diabetes
      and the risk of multiple cancers, including hepatocellular, pancreatic,
      endometrial, colorectal, breast, kidney, bladder, gastric, and ovarian cancer,
      non-Hodgkin lymphoma, T cell lymphoma and leukemia. There are multiple potential
      biological mechanisms that may link type 2 diabetes, obesity and cancer. Insulin
      resistance and hyperinsulinemia may lead to direct activation of the insulin
      receptors on tumor cells and promote tumor growth. Other potential mechanisms
      include increased circulating, local or bioavailable insulin-like growth factor
      1, hyperglycemia, dyslipidemia, increased circulating or local estrogen,
      adipokines and direct and indirect effects of inflammatory cytokines.
      Epidemiological studies have had conflicting results regarding the associations
      between various classes of antidiabetic medication and cancer development. Animal
      studies have demonstrated increased tumor growth with certain medications, but
      their relevance to humans is uncertain. Metformin may, however, have protective
      effects on cancer development and may improve survival in patients with cancer.
      CONCLUSION: We describe the current understanding of the links among diabetes,
      antidiabetic medication and cancer risk. We highlight some of the issues that
      should be addressed in the future to prevent cancer development and death in
      those with diabetes.

PMID- 23974780
TI  - Anatomic evaluation of the vertical face-lift in cadavers.
AB  - IMPORTANCE: This study investigates how different orientations of tension vectors
      affect the amount of soft-tissue lift in specific cervicofacial regions.
      OBJECTIVES: To compare differences in cosmetic neck and face changes generated by
      3 different face-lift techniques, to quantify the amount of lift across different
      points on the face, and to quantify changes in platysmal dehiscence in each of 3
      standard superficial musculoaponeurotic system plication face-lift techniques
      applied to fresh-frozen cadaver heads. DESIGN, SETTING, AND PARTICIPANTS: Ten
      cadaver heads in an academic tertiary care center. INTERVENTION(S): Three
      different superficial musculoaponeurotic system plication rhytidectomy procedures
      were conducted in the following sequence: (1) vertical tension vector plication
      (vertical lift), (2) superolateral tension vector plication (superolateral lift),
      and (3) superolateral tension vector plication combined with midline platysmal
      plication (superolateral lift with platysmal plication). MAIN OUTCOMES AND
      MEASURES: After completion of each technique, the amount of lift at 4 standard
      key points was measured and recorded, and differences in lift at the key points
      were analyzed. RESULTS: Vertical lift was associated with greater total lift than
      superolateral lift alone or superolateral lift with platysmal plication (P < .001
      for both). Platysmal dehiscence increased from baseline measurements after
      superolateral lift and decreased after vertical lift (P = .002 for both).
      CONCLUSIONS AND RELEVANCE: Our findings establish how different orientations of
      tension vectors applied during face-lift surgery achieve different structural
      changes to various key points across the face. This study helps the face-lift
      surgeon and student understand the underlying structural anatomic changes
      associated with different face-lift techniques, which ultimately result in
      different cosmetic outcomes. LEVEL OF EVIDENCE: NA.

PMID- 23974782
TI  - Correcting misconceptions about compounding bioidentical hormones: a review of
      the literature.
AB  - There are many misconceptions about the profession of pharmaceutical compounding
      and the preparation of bioidentical hormones used in hormone replacement therapy.
      These misconceptions are unfounded, because compounding is regulated by
      individual state boards of pharmacy, and compounded bioidentical hormones are
      prepared only when prescribed by a physician who has made a professional judgment
      in the interest of the patient. Physicians and the pharmacists who compound
      bioidentical hormones have not only the right but also the responsibility to be
      aware of current information published in the scientific literature concerning
      any prescribed medication. 

PMID- 23974781
TI  - Transcatheter valve implantation improves central sleep apnoea in severe aortic
      stenosis.
AB  - AIMS: Severe cardiac disorders predispose to central sleep apnoea (CSA). We
      sought to examine the relationship between severe aortic stenosis, sleep
      disordered breathing (SDB), and CSA before and after transcatheter aortic valve
      implantation (TAVI). METHODS AND RESULTS: Twenty-nine patients (81+/-6 yrs, 41%
      male, LVEF 48+/-14%) with severe aortic stenosis and high surgical risk underwent
      polygraphy before and three months after TAVI. Patients with an apnoea-hypopnoea
      index (AHI) >5/hr were considered to have SDB. SDB with >=50% absence of both
      airflow and ventilatory effort was defined as CSA. Twenty-one of 29 patients
      (72%) had SDB (6/6/9 mild, moderate, and severe, respectively), 12 (41%) with CSA
      (0/4/8) and 9 (31%) with obstructive sleep apnoea (7/2/0). There was a strong
      correlation of CSA with LVEDP before TAVI (r=0.74, p=0.024), but not with LVEF,
      systolic pulmonary artery pressure or NT pro-BNP. After TAVI, AHI improved
      significantly, particularly in the CSA group (from 43.5+/-17.5 to 19.4+/-12.9/hr,
      p<0.001). Prevalence and severity of SDB were reduced from 72% to 59% (6/6/9 to
      7/8/2 patients), triggered by the significant improvement of CSA. CONCLUSIONS:
      Patients with severe aortic stenosis display a high prevalence of SDB,
      particularly of CSA. Definitive treatment with TAVI greatly resolved SDB in the
      CSA subgroup.

PMID- 23974783
TI  - The history of progesterone.
AB  - Progesterone, the principal pregestational hormone of the body, is metabolized
      and produced in the corpus luteum via conversion of pregnenolone. Progesterone
      functions to prepare the uterus for the reception and development of the
      fertilized ovum by transformation of the endometrium from the proliferative to
      the secretory stage. By suppressing menstruation and uterine contractility,
      progesterone is extremely important in the maintenance of pregnancy. The two most
      frequent uses for progestins are contraception and hormone replacement therapy.
      This article provides a brief history of the discovery of progesterone and its
      therapeutic development and discusses the major challenges and advancements in
      steroid chemistry. 

PMID- 23974784
TI  - The politics of hormone replacement therapy.
AB  - This issue of the International Journal of Pharmaceutical Compounding includes
      several articles about hormone replacement therapy. Some of those articles are
      similar in content, but they have an important message in common: Patients,
      physicians, and compounding pharmacists should not be swayed by the
      misconceptions about compounding prescriptions for patients requiring hormone
      replacement therapy, nor should they be influenced by misinformation about the
      profession of pharmaceutical compounding. The pharmaceutical industry drives and
      funds both the legislative control and minimization of pharmacy compounding and,
      by disseminating misinformation and presenting biased viewpoints, openly
      discourages compounding. Political activists are working for both sides-for the
      pharmaceutical industry and for the profession of comounding-and such politics
      will continue for many years. 

PMID- 23974786
TI  - Common acronyms used by health professionals who prescribe or prepare hormone
      replacement therapy.

PMID- 23974785
TI  - Premarin: the intriguing history of a controverisal drug.
AB  - Premarin, a complex of conjugated equine estrogens manufactured by Wyeth for use
      as hormone replacement therapy in women, was originally developed by the Canadian
      pharmaceutical firm Ayerst, McKenna and Harrison. The name Premarin was coined
      from pregnant mare urine, from which the estrogen complex was isolated. Although
      the complete composition of Premarin and its active components remains
      undisclosed or unknown, Wyeth reports that it contains a mixture of 10 estrogens.
      The history of Premarin is entangled in a fascinating story of human intrigue
      involving ingenuity, influence, controversy, animal rights, competition, money,
      protection of stockholders, government regulatory power, patient rights,
      emotions, greed, power, personal and professional freedom, state rights, and
      perhaps even, ultimately, constitutional issues. As the saga of Premarin evolves,
      it no doubt will continue to be one of the more interesting and compelling
      stories of the practice of pharmacy. 

PMID- 23974787
TI  - The lived experience of perimenopausal and menopausal women undergoing treatment
      with bioidentical human hormones.
AB  - The qualitative study described in this article includes excerpts from the thesis
      of NaRisa Y. Holt-Waldo, MSN,RN. Research on the lived experience of women
      undergoing treatemnt with bioidentical human hormone replacement therapy for the
      relief of perimenopausal or menopausal symptoms was conducted in the College of
      Nursing at the University of Texas at Tyler, Texas. Implications of the study
      results for the fields of nursing and pharmacy are also presented.

PMID- 23974788
TI  - Obtaining accreditation by the pharmacy compounding accreditation board, part 1:
      an overview.
AB  - An organization's performance is constantly compared with that of other similar
      businesses and is challenged to comply with industry standards. Accreditation by
      an external standard-setting body officially sanctions a business and
      differentiates it from competitors. Various industries have external standard
      setting entities to which they can apply for accreditation. Compounding
      pharmacists are encouraged to seek accreditation by the Pharmacy Compounding
      Accreditation board. The accreditation process may seem daunting, but it can be
      simplified and more clearly understood if you divide the application procedure
      into sections, involve your entire pharmacy staff, and discuss the application
      prodedure with past applicants. One of the most exciting new developments in the
      world of compounding is the opportunity for a pharmacy to obtain accreditation.
      Other healthcare organizations have had that opportunity for years: Hospitals are
      accredited by the Joint Commission on Accreditation of healthcare Organizations
      (JCAHO); home care organizations are credentialed by both the Accreditation
      Commission for Health Care, Inc., and the JCAHO; and health management
      organizations and preferred provider organizations are accredited by the National
      Council for Quality Assurance. All those industry segments have realized the
      value of measuring their organization's performance against national standards.
      The first question that a compounder may ask is, "Why is accreditation
      important?" For me, the answer is simple. I have yet to see pharmacy advertising
      that states, "Our pharmacy meets minimal standards and we have the least
      qualified staff in town." Every pharmacy says that it is excellent. However,
      because of certain current media issues (steroid scandals American Medical
      Association resolutions, congressional hearings), compounders must prove to
      physicians and patients that their pharmacy meets a high standard, and
      accreditation by the Pharmacy Compounding Accreditation Board (PCAB) is that
      proof of quality. Athough acquiring accreditation by the PCAB is a great
      opportunity for differentiating your pharmacy from others, extensive preparation
      may be required to achieve full compliance with the specified standards. This
      article addresses some of the questions posed by compounders about accreditation,
      such as: How do I initiate the process of application for accreditation? What is
      required during that process? Which standard operating procedures (SOPs) are
      required? How much time will be required? Will I need to change what we do? What
      do ceratin standards mean? What will the survey process be like? How long does
      the preparation preocess take? How does a compounding pharmacy prepare for
      accreditation? 

PMID- 23974789
TI  - Update on the proposed revision process for United States phamacopeia chapter 797
      pharmacuetical compounding-sterile preparations.
AB  - Information contained in published standards and/or guidelines must be reviewed
      and revised as required. Those practitioners affected by published standards
      and/or guidelines should understand and be involved in the review and revision
      procedures. The United States Pharmacopeial Convention, Inc.'s standards set
      forth in the United States Pharmacopeia 30-National Formulary 25, the most recent
      version of this publication, as well as those included in their publication
      titled USP Pharmacists' Pharmacopeia, is an example of a standard-setting body
      that encourages and welcomes the participation of compounding pharmacists to be
      involved in the review and revision process. 

PMID- 23974790
TI  - Quality-Control Analytical Methods: Logbooks and Documentation forms.

PMID- 23974791
TI  - Basics of compounding: the responsibilities of compounding personnel in
      implementing United States pharmacopeia chapter 797 pharmaceutical compounding
      sterile preparations, part 2.
AB  - United States Pharmacopeia Chapter 797 Pharmaceutical Compounding-Sterile
      Preparations pertains to all preadministration manipulations and procedures
      involved in preparation of sterile compounds for application, implantation,
      infusion, inhalation, injection, insertion, instillation, or irrigation,
      including preparation, storage, and transportation. The chapter does not pertain
      to actual clinical administration of compounded sterile preparations to patients.
      The intent of Chapter 797 is simply to prevent patient harm and fatalities that
      may result from nonsterility, excessive endotoxin load, large content errors in
      strength of correct ingredients, or the presence of incorrect ingredients.
      Because the achievement of sterility requires that facilities meet minimum
      cleanliness standards, that personnel be trained adequately and undergo periodic
      testing and training in sterilization techniques, and that appropriate principles
      and practices be applied to sustain solution stability, compliance to Chapter 797
      should be the goal of any facility where sterile preparations are compounded.
      Many pharmacies have already become compliant with Chapter 797, and those that
      have already met the new standards seem to support them strongly. 

PMID- 23974792
TI  - Statistical analysis of barrier isolator/glovebox glove failure.
AB  - In response to new, stricter safety requirements set out by the federal
      government, compounding pharmacists are investigating applications and processes
      appropriate for their facilities. One application, cutrrently used by many
      industries, was developed by Los Alamos National Laboratories for defense work. A
      barrier isolator or "glovebox" is a containment device that allows work within a
      sealed space while providing protection for people and the environment. Though
      knowledge of glove box use and maintenance has grown, unplanned breaches (e.g.,
      glove failures) remain a concern. Recognizing that effective maintenance
      procedures can minimize breaches, we analyzed data drawn from glove failure
      records of Los Alamos National Laboratory's Nuclear Materials Technology Division
      to evaluate current inventory strategy in light of actual performance of the
      various types of gloves. This report includes a description of the statistical
      methods employed. The results of our analysis pinpointed the most frequently
      occurring causes of glove failure and revealed a significant imbalance between
      the current glove replacement schedule and the rate of glove failures in a much
      shorter period. We concluded that, to minimize unplanned breaches, either the
      replacement period needs to be adjusted or causes of failure eliminated or
      reduced. 

PMID- 23974793
TI  - Chemical stability of cyproheptadine hydrochloride in an oral liquid dosage form.
AB  - The chemical stability of cyproheptadine hydrochloride in an oral liquid dosage
      form was studied by using a stability-indicating high-performnace liquid
      chromatographic assay method that was developed in our laboratory. The
      concentrations of the drug were directly related to peak heights, with an R value
      of 0.991. The percent relative standard deviation based on five injections was
      1.6. The products of decomposition and excipients present in the dosage forms did
      not interfere with the developed assay method. The mixture was stable for at
      least 180 days when stored in amber-colored glass bottles at room temperature.
      the pH value of the mixture remained constant at 3.7 after 180 days of storage,
      and the physical appearance of the formulation did not change during the study
      period. 

PMID- 23974794
TI  - PostScription: Thousands of Unapproved New Drugs are on the U.S. Market, Part 1.

PMID- 23974795
TI  - Ursodeoxycholyl lysophosphatidylethanolamide inhibits lipoapoptosis by shifting
      fatty acid pools toward monosaturated and polyunsaturated fatty acids in mouse
      hepatocytes.
AB  - Ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) is a hepatoprotectant in
      inhibiting apoptosis, inflammation, and hyperlipidemia in mouse models of
      nonalcoholic steatohepatitis (NASH). We studied the ability of UDCA-LPE to
      inhibit palmitate (Pal)-induced apoptosis in primary hepatocytes and delineate
      cytoprotective mechanisms. We showed that lipoprotection by UDCA-LPE was mediated
      by cAMP and was associated with increases in triglycerides (TGs) and
      phospholipids (PLs). An inhibitor of cAMP-effector protein kinase A partially
      reversed the protective effects of UDCA-LPE. Lipidomic analyses of fatty acids
      and PL composition revealed a shift of lipid metabolism from saturated Pal to
      monounsaturated and polyunsaturated fatty acids, mainly, oleate,
      docosapentaenoate, and docosahexaenoate. The latter two omega-3 fatty acids were
      particularly found in phosphatidylcholine and phosphatidylserine pools. The
      catalysis of Pal by stearoyl-CoA desaturase-1 (SCD-1) is a known mechanism for
      the channeling of Pal away from apoptosis. SCD-1 protein was upregulated during
      UDCA-LPE lipoprotection. SCD-1 knockdown of Pal-treated cells showed further
      increased apoptosis, and the extent of UDCA-LPE protection was reduced. Thus, the
      major mechanism of UDCA-LPE lipoprotection involved a metabolic shift from toxic
      saturated toward cytoprotective unsaturated fatty acids in part via SCD-1. UDCA
      LPE may thus be a therapeutic agent for treatment of NASH by altering distinct
      pools of fatty acids for storage into TGs and PLs, and the latter may protect
      lipotoxicity at the membrane levels. 

PMID- 23974796
TI  - Identification of a long non-coding RNA-associated RNP complex regulating
      metastasis at the translational step.
AB  - Long non-coding RNAs (lncRNAs) are a novel class of regulatory genes that play
      critical roles in various processes ranging from normal development to human
      diseases such as cancer progression. Recent studies have shown that lncRNAs
      regulate the gene expression by chromatin remodelling, transcription, splicing
      and RNA decay control, enhancer function, and epigenetic regulation. However,
      little is known about translation regulation by lncRNAs. We identified a
      translational regulatory lncRNA (treRNA) through genome-wide computational
      analysis. We found that treRNA is upregulated in paired clinical breast cancer
      primary and lymph-node metastasis samples, and that its expression stimulates
      tumour invasion in vitro and metastasis in vivo. Interestingly, we found that
      treRNA downregulates the expression of the epithelial marker E-cadherin by
      suppressing the translation of its mRNA. We identified a novel ribonucleoprotein
      (RNP) complex, consisting of RNA-binding proteins (hnRNP K, FXR1, and FXR2),
      PUF60 and SF3B3, that is required for this treRNA functions. Translational
      suppression by treRNA is dependent on the 3'UTR of the E-cadherin mRNA. Taken
      together, our study indicates a novel mechanism of gene regulation by lncRNAs in
      cancer progression. 

PMID- 23974797
TI  - WASH inhibits autophagy through suppression of Beclin 1 ubiquitination.
AB  - Autophagy degrades cytoplasmic proteins and organelles to recycle cellular
      components that are required for cell survival and tissue homeostasis. However,
      it is not clear how autophagy is regulated in mammalian cells. WASH (Wiskott
      Aldrich syndrome protein (WASP) and SCAR homologue) plays an essential role in
      endosomal sorting through facilitating tubule fission via Arp2/3 activation.
      Here, we demonstrate a novel function of WASH in modulation of autophagy. We show
      that WASH deficiency causes early embryonic lethality and extensive autophagy of
      mouse embryos. WASH inhibits vacuolar protein sorting (Vps)34 kinase activity and
      autophagy induction. We identified that WASH is a new interactor of Beclin 1.
      Beclin 1 is ubiquitinated at lysine 437 through lysine 63 linkage in cells
      undergoing autophagy. Ambra1 is an E3 ligase for lysine 63-linked ubiquitination
      of Beclin 1 that is required for starvation-induced autophagy. The lysine 437
      ubiquitination of Beclin 1 enhances the association with Vps34 to promote Vps34
      activity. WASH can suppress Beclin 1 ubiquitination to inactivate Vps34 activity
      leading to suppression of autophagy. 

PMID- 23974798
TI  - Fluoride releasing and enamel demineralization around orthodontic brackets by
      fluoride-releasing composite containing nanoparticles.
AB  - INTRODUCTION: Fluoride-containing materials have been suggested to control enamel
      demineralization around orthodontic brackets during the treatment with fixed
      appliances. The improvement of their properties has been made through
      innovations, such as the application of nanotechnology by incorporation of
      nanofillers. OBJECTIVE: This in vitro study evaluated the capacity of fluoride
      releasing and enamel demineralization inhibition of fluoride-releasing nanofilled
      cement around orthodontic brackets using an artificial caries biofilm model.
      MATERIALS AND METHODS: Forty bovine enamel discs were selected by evaluating
      surface microhardness and randomized into four groups (n = 10): non-fluoride
      releasing microfilled composite, fluoride-releasing microfilled composite, resin
      modified glass ionomer cement (RMGI), and fluoride-releasing nanofilled composite
      (FN). After brackets bonding in each disc, the specimens were subjected to a
      cariogenic challenge through a Streptococcus mutans biofilm model. After the
      experimental period, the biofilm formed around the brackets was collected for
      fluoride analysis and the mineral loss around the brackets was determined by
      integrated demineralization via cross-sectional microhardness measurement at 20
      and 70 MUm from the bracket margin. Additionally, samples of each group were
      subjected to energy-dispersive X-ray spectroscopy (EDX) analysis examined under a
      scanning electron microscopy (SEM). ANOVA followed by Tukey test were applied for
      fluoride concentration and mineral loss data, respectively. RESULTS: At both
      distances, only RMGI statistically differed from the other groups presenting the
      lowest demineralization, although there was a trend to a lower demineralization
      of enamel around brackets in FN group. Similar condition was found to fluoride
      concentration and EDX/SEM analysis. CONCLUSIONS: Under the cariogenic exposure
      condition of this study, the fluoride-releasing nanofilled material had similar
      performance to fluoride-releasing microfilled materials. CLINICAL RELEVANCE: The
      presence of nanofillers in the fluoride-releasing materials studied did not
      promote further benefits against caries lesion development around brackets and
      presented inferior demineralization inhibition than the resin-modified glass
      ionomer material.

PMID- 23974799
TI  - Fluoride release and mechanical properties after 1-year water storage of recent
      restorative glass ionomer cements.
AB  - OBJECTIVES: The objective of this study was to evaluate the relationships between
      fluoride release and mechanical properties after 1-year water storage of five
      recent restorative glass ionomer cements (GICs). MATERIALS AND METHODS: Five
      GICs, FujiIX GP EXTRA (FEX), FujiIX GP (FIX), GlasIonomer FX-II (GFX), Ketac
      Molar Easymix (KME), and Riva Self Cure (RSC), were examined. Cumulative fluoride
      release, compressive strength, and surface hardness were measured up to 1-year
      storage (n = 5), and analyzed with one-way or two-way ANOVA and Tukey HSD test
      (alpha = 0.05). Elemental compositions before and after 1-year storage were also
      examined (n = 3). RESULTS: The amounts of fluoride release were significantly
      different among the products. The highest amount of fluoride release occurred
      during the first day. Then, the amount of fluoride release rapidly decreased and
      still continued until 1-year storage. Compressive strengths indicated that two
      main factors were significant (GFX < FEX = RSC < FIX < KME; 1 day < 1 week = 1
      month = 3 months = 6 months = 1 year), but surface hardness showed a slightly
      different tendency (GFX = RSC < FEX = FIX = KME; 1 year < 1 day < 1 week = 1
      month = 3 months = 6 months). Significant correlation was found between decrease
      of silicon and decrease rate of the surface hardness. CONCLUSIONS: Fluoride
      releases were detected up to 1-year storage, but the mechanical properties
      slightly decreased due to decrease of Si after 1-year storage. Elution of Si
      instead of fluoride release was considered more critical to deteriorate the
      mechanical properties of GICs. CLINICAL RELEVANCE: Fluoride released for 1-year
      water storage will contribute to secondary caries prevention. The amount of
      fluoride release did not affect these mechanical properties. These results
      indicate the usefulness of these GICs.

PMID- 23974800
TI  - Push-out bond strength of three calcium silicate cements to root canal dentine
      after two different irrigation regimes.
AB  - OBJECTIVES: The aim of this study was to compare the push-out bond strength of
      three calcium silicate cements to dentine after two different irrigation regimes.
      MATERIALS AND METHODS: One hundred eighty 2-mm-thick root sections were prepared.
      The sections were divided into three main groups (n = 60). In group A, the
      sections were immersed in 1 % NaOCl for 3 min. In group B, the sections were
      immersed in 17 % EDTA for 3 min followed by 1 % NaOCl for the same period of
      time. In group C (control group), no irrigation was applied to the sections. The
      samples from each group were divided into four subgroups (n = 15). In subgroups
      A1, B1 and C1, DiaRoot BioAggregate; in subgroups A2, B2 and C2, MTA-Angelus and
      in subgroups A3, B3 and C3, MM-MTA were mixed with hand-mixing. In subgroups A4,
      B4 and C4, MM-MTA was mixed with auto-mixing. The mixed cements were then placed
      into cavities with a carrier. The samples were submitted to the push-out test and
      were loaded. All the data were analysed with one-way analysis of variance and the
      Tukey HSD multiple comparisons (p < 0.05). RESULTS: There were no statistically
      significant differences between the irrigation regimes regardless of the used
      materials. The resistance to displacement in subgroup B4 was significantly
      greater than that presented by subgroups A3, B3 and C3 (p < 0.05) while not
      different than all other groups. CONCLUSIONS: Irrigation regimes had not affected
      the push-out bond strength of the calcium silicate cements. Also, strength of
      auto-mixed MM-MTA was similar to the other cements. CLINICAL RELEVANCE: The novel
      calcium silicate cements would be a potentially useful material in endodontic
      procedures with favourable properties.

PMID- 23974801
TI  - Atraumatic restorative treatment and Carisolv use for root caries in the elderly:
      2-year follow-up randomized clinical trial.
AB  - OBJECTIVES: New preventive and treatment strategies are required to address the
      high prevalence of caries among the elderly. The main objective of this study was
      to analyze the effectiveness of Carisolv(r) gel to improve the clinical behavior
      of restorations obtained by atraumatic restorative treatment (ART) in root caries
      of elderly patients. A secondary objective was to determine the factors
      associated with the failure of ART restorations after a 2-year follow up.
      MATERIAL AND METHODS: A randomized controlled trial with 2-year follow-up was
      designed for this purpose. Candidate caries lesions were randomly assigned to an
      ART group for root caries treatment with the conventional ART technique, filling
      with glass ionomer, or an ART + Carisolv(r) gel for the same ART plus the
      application of a caries solvent (Carisolv(r)). Evaluations were conducted at 6,
      12, and 24 months. RESULTS: A total of 81 restorations were performed, 37 in the
      ART group and 44 in the ART + Carisolv(r) gel group, with 22 and 26 restorations,
      respectively, surviving at the end of the 24-month follow-up. Survival rates at
      24 months did not significantly differ between ART (63 %) and ART + Carisolv(r)
      gel (62 %) restorations. The best model for predicting the failure of the
      restorations included the number of tooth-brushings/day, the presence or not of
      prosthesis, the anterior or posterior location of the tooth, and the baseline
      plaque level. CONCLUSION: The application of Carisolv does not modify the
      survival rate of ART restorations in elderly patients. CLINICAL RELEVANCE: The
      use of Carisolv gel does not improve the outcomes of atraumatic restorative
      treatment.

PMID- 23974802
TI  - Pulmonary rehabilitation in clinical routine: a follow-up study.
AB  - OBJECTIVE: The effect of rehabilitation for chronic obstructive pulmonary disease
      has been well-documented in randomized controlled trials. Evidence-based
      guidelines support rehabilitation programmes for chronic obstructive pulmonary
      disease, but knowledge of their outcome in clinical practice is limited. The aim
      of this study was to assess the outcome of a clinical routine rehabilitation
      programme for chronic obstructive pulmonary disease implemented by a Danish
      regional hospital. MATERIAL AND METHODS: Changes in walk-distance (6-min walk
      distance test; 6MWD), dyspnoea (Medical Research Council dyspnoea scale; MRC) and
      health-related quality of life (Short-Form 36; SF-36) were compared between and
      within completers and non-completers from baseline to the end of clinical routine
      rehabilitation, and at 6 and 12 months. The 8-week clinical routine
      rehabilitation comprised bi-weekly 90-min sessions of patient education and
      physical training. RESULTS: The hospital treated 521 patients during the study
      period. Of these, 175 were invited to join the study, 148 participated at
      baseline, and 98 at the 12-month follow-up. Completers' 6MWD was sustained from
      baseline to the end of clinical routine rehabilitation, but had declined by 12
      months. Dyspnoea and health-related quality of life did not change. Seventy-five
      percent of completers felt better or much better after rehabilitation.
      CONCLUSION: The failure of completers to achieve expected outcomes shows a need
      for a stronger implementation effort and continuous quality control. Successful
      implementation in clinical routine requires targeted recruitment and overall
      programme improvement in general, and a stronger focus on physical training and
      staff competences.

PMID- 23974803
TI  - Normative data for neuromuscular assessment of the hand-arm vibration syndrome
      and its retrospective applications in Korean male workers.
AB  - PURPOSE: The purpose of this study was to describe normative data for the
      neuromuscular assessments of the hand-arm vibration syndrome (HAVS) in Korean.
      METHODS: Data for the vibrotactile perception threshold (VPT) at three
      frequencies (31.5, 125, and 250 Hz), the hand grip strength (HGS), the finger
      pinch strength (FPS), the finger tapping test, and the Purdue pegboard tests were
      collected from 120 male office workers aged 30-59 years with no prior history of
      regular use of handheld vibrating tools. The collected data were compared with
      the results of a similar study of shipbuilding workers in order to investigate
      the diagnostic utility of clinical test for HAVS. RESULTS: The mean VPT values
      indicate that no significant differences were observed between the dominant and
      non-dominant hands or between the index and little fingers. The age group of 30s
      was highly sensitive to vibration input with a peak in sensitivity at 125 Hz
      among all age groups. In neuromuscular performance, dominant hands are usually
      more accurate, dexterous, and functionally quicker than non-dominant hands. The
      index finger was superior to the little finger in the finger tapping counts (p <
      0.05). Also, FPS was greater in the index finger than in the middle finger (p <
      0.05). The HGS of dominant hands was significantly stronger than that of non
      dominant hands (p < 0.05). When the normative data were compared with the data of
      shipyard workers exposed to vibration, there were statistically significant
      differences in VPT and neuromuscular functions. CONCLUSIONS: The current data can
      be used to evaluate HAVS in Korean male workers. Age is an important factor for
      VPT.

PMID- 23974804
TI  - Brain-expressed imprinted genes and adult behaviour: the example of Nesp and
      Grb10.
AB  - Imprinted genes are defined by their parent-of-origin-specific monoallelic
      expression. Although the epigenetic mechanisms regulating imprinted gene
      expression have been widely studied, their functional importance is still
      unclear. Imprinted genes are associated with a number of physiologies, including
      placental function and foetal growth, energy homeostasis, and brain and
      behaviour. This review focuses on genomic imprinting in the brain and on two
      imprinted genes in particular, Nesp and paternal Grb10, which, when manipulated
      in animals, have been shown to influence adult behaviour. These two genes are of
      particular interest as they are expressed in discrete and overlapping neural
      regions, recognised as key "imprinting hot spots" in the brain. Furthermore,
      these two genes do not appear to influence placental function and/or maternal
      provisioning of offspring. Consequently, by understanding their behavioural
      function we may begin to shed light on the evolutionary significance of imprinted
      genes in the adult brain, independent of the recognised role in maternal care. In
      addition, we discuss the potential future directions of research investigating
      the function of these two genes and the behavioural role of imprinted genes more
      generally. 

PMID- 23974805
TI  - Is nocturia of young adulthood a remnant of childhood nocturnal enuresis?
AB  - INTRODUCTION AND HYPOTHESIS: Nocturia and nocturnal enuresis (NE) share similar
      aetiopathological factors, and may represent two different situations involving
      the same underlying issue. In this study, we tried to evaluate the relation
      between NE of childhood and nocturia of young adulthood. METHODS: A total of 577
      female university students aged 17-24 years were included in the survey. A face
      to-face questionnaire was administered concerning present nocturia and past NE
      history. A non-validated questionnaire, created by the authors, was used to
      evaluate the presence and the frequency of childhood NE and present nocturia. All
      participant data were checked by telephone contact with their parents. RESULTS:
      The overall prevalence rates of nocturia and history of nocturnal enuresis in the
      study population were 8.6 % and 15 % respectively. Sixteen per cent of nocturics
      and 15 % of non-nocturics had a history of childhood NE (p = 0.837). The
      childhood NE was graded as severe or infrequent. The presence of nocturia was
      compared between participants with severe NE and infrequent NE, and no
      significant difference was observed (11.1 % vs 7.8 %, p = 0.713). Nocturia
      frequency was compared with the history of childhood NE and we found that as the
      nocturia frequency increased, the rate of childhood NE also increased.
      CONCLUSIONS: There was no relation between young adulthood nocturia and childhood
      NE in our study population, but as the severity of nocturia increased, the
      relation between nocturia and NE became more relevant.

PMID- 23974806
TI  - Indian government shelves plans for mercy killing law.

PMID- 23974807
TI  - Child poverty and malnutrition rise in Spain as austerity measures bite.

PMID- 23974808
TI  - Methadone prescribing should continue in Scotland, says review.

PMID- 23974823
TI  - Concurrent and adjuvant temozolomide-based chemoradiotherapy schedules for
      glioblastoma. Hypotheses based on two prospective phase II trials.
AB  - AIM: To investigate the impact of nonstandard concomitant temozolomide (TMZ)
      administration in two prospective phase II studies for glioblastoma (GBM).
      PATIENTS AND METHODS: From October 2000 to June 2008, 104 patients were enrolled
      in two studies: 25 in RT-TMZ-10.00 and 79 in RT-TMZ-01.04. Adjuvant radiotherapy
      (RT) was used with a total dose of 59.4 Gy (1.8 Gy/day). Patients received
      concomitant TMZ (75 mg/m(2)/day) from Monday to Friday during the first and last
      weeks of RT in the RT-TMZ-10.00 study and from Monday to Friday during all weeks
      of RT in the RT-TMZ-01.04 trial. Adjuvant TMZ (200 mg/m(2)) was administered for
      5 days every 28 days. RESULTS: Median progression-free (PFS) and overall survival
      (OS) were 9 and 16 months, respectively, with no significant difference between
      the two groups (p = 0.5 and 0.14, respectively). The 2- and 5-year OS rates were
      32 and 3 %, respectively, and similar to those observed with standard treatment
      regimens. CONCLUSION: Our data support the hypothesis that adjuvant TMZ is more
      important than concomitant chemotherapy (CH) and that RT is the more important
      element of the concomitant treatment schedule.

PMID- 23974824
TI  - Definitive radiation therapy for treatment of laryngeal carcinoma: impact of
      local relapse on outcome and implications for treatment strategies.
AB  - PURPOSE: The purpose of this work was to evaluate outcome after radiotherapy (RT)
      for laryngeal carcinoma and investigate effects of local relapse on ultimate
      disease control, including surgical salvage procedures. METHODS AND MATERIALS: In
      all, 435 patients with laryngeal carcinoma (cT1-cT4a) treated with primary RT
      were retrospectively analyzed. Uni- and multivariate analyses were performed to
      identify prognostic factors for local relapse-free survival and overall survival.
      RESULTS: Median follow-up was 38 months (range 1-144 months). The cumulative
      frequency of local recurrence was dependent on T stage: cT1 tumors 10%, cT2 18%,
      cT3 23%, and cT4 36% (p<0.001). Salvage surgery for local persistent/recurrent
      disease was performed in 59 of 78 patients (76%). The ultimate local control
      rates at 5 years (including salvage therapy) were 98, 98, 87, and 68% for cT1,
      cT2, cT3, and cT4 tumors (p<0.001), respectively. For the patients who developed
      local recurrence, the 5-year ultimate local control rates were 80, 88, 55, and
      26% (p<0.001), respectively. Overall survival at 5 years was 68% for patients
      without local relapse and 50% for patients experiencing local failure (p<0.001).
      In univariate analysis, cT stage, cN stage, and tumor volume were statistically
      significant associated with local relapse-free survival. In multivariate analysis
      for the cT3-4 tumors, only tumor volume remained statistically significant (HR
      1.017, p=0.001) for local relapse-free survival. CONCLUSION: Local control rates
      for cT1-2 laryngeal carcinomas are favorable and in concordance with previous
      reports and most recurrences are salvaged. For cT3-4 tumors treated with RT
      alone, initial local control rates are moderate, and in 60% of recurring cases
      salvage surgery is attempted, with ultimate local control being achieved in only
      a subset. For voluminous, locally advanced laryngeal tumors, more aggressive
      treatment modalities should be considered, including upfront laryngectomy or
      radiochemotherapy.

PMID- 23974825
TI  - A decision-making framework for adaptive pain management.
AB  - Pain management is a critical international health issue. The Eugene McDermott
      Center for Pain Management at The University of Texas Southwestern Medical Center
      conducted a two-stage interdisciplinary pain management program that considers a
      wide variety of treatments. Prior to treatment (beginning of Stage 1), an
      evaluation records the patient's pain characteristics, medical history and
      related health parameters. A treatment regime is then determined. At the midpoint
      of the program (beginning of Stage 2), an evaluation is conducted to determine if
      an adjustment in the treatment should be made. A final evaluation is conducted at
      the end of the program to assess final outcomes. We structure this decision
      making process using dynamic programming (DP) to generate adaptive treatment
      strategies for this two-stage program. An approximate DP solution method is
      employed in which state transition models are constructed empirically based on
      data from the pain management program, and the future value function is
      approximated using state space discretization based on a Latin hypercube design
      and artificial neural networks. The optimization seeks for treatment plans that
      minimize treatment dosage and pain levels simultaneously. 

PMID- 23974826
TI  - Anaerobic performance in children with cerebral palsy compared to children with
      typical development.
AB  - PURPOSE: Using a locomotor-based field test of anaerobic performance, this study
      compared the anaerobic performance of children with spastic cerebral palsy (CP)
      who walk without support with that of peers who are typically developing.
      METHODS: The Muscle Power Sprint Test was performed by 159 children with CP (102
      boys, mean age 9.7 +/- 1.5 years; and 57 girls, mean age 9.5 +/- 1.6 years)
      classified at Gross Motor Function Classification System level I (n = 115) or
      level II (n = 44) and 376 children with typical development (175 boys, mean age
      8.9 +/- 1.8 years; and 201 girls, mean age 9.0 +/- 1.7 years). RESULTS: The
      anaerobic performance of the children with CP was lower than that of peers with
      typical development. CONCLUSIONS: The difference between the 2 groups increased
      with height, especially for the children with CP classified at Gross Motor
      Function Classification System level II. Children with CP appear to have impaired
      anaerobic performance.

PMID- 23974827
TI  - Commentary on "Anaerobic performance in children with cerebral palsy compared to
      children with typical development".

PMID- 23974828
TI  - The impact of the Oncotype Dx breast cancer assay in clinical practice: a
      systematic review and meta-analysis.
AB  - The impact of the Oncotype Dx (ODX) breast cancer assay on adjuvant chemotherapy
      (ACT) treatment decisions has been evaluated in many previous studies. However,
      it can be difficult to interpret the collective findings, which were conducted in
      diverse settings with limited sample sizes. We conducted a systematic review and
      meta-analysis to synthesize the results and provide insights about ODX utility.
      Studies, identified from PubMed, Embase, ASCO, and SABCS, were included if
      patients had ER+, node -, early-stage breast cancer, reported use of ODX to
      inform actual ACT decisions. Information was summarized and pooled according to:
      (1) distribution of ODX recurrence scores (RS), (2) impact of ODX on ACT
      recommendations, (3) impact of ODX on ACT use, and (4) proportion of patients
      following the treatment suggested by the ODX RS. A total of 23 studies met
      inclusion criteria. The distribution of RS categories was 48.8 % low, 39.0 %
      intermediate, and 12.2 % high (21 studies, 4,156 patients). ODX changed the
      clinical-pathological ACT recommendation in 33.4 % of patients (8 studies, 1,437
      patients). In patients receiving ODX, receipt of ACT were: 28.2 % overall, 5.8 %
      low, 37.4 % intermediate, and 83.4 % high. Low RS patients were significantly
      more likely to follow the treatment suggested by ODX versus high RS patients RR:
      1.07 (1.01-1.14) [corrected].The pooled results are consistent with most
      individual studies to date. The increased proportion of intermediate scores
      relative to original estimates may have implications for the clinical utility and
      cost impacts of testing. In addition, low versus high RS patients were
      significantly more likely to follow the ODX results, suggesting a tendency toward
      less aggressive treatment, despite a high ODX RS. Finally, there was a lack of
      studies on the impact of ODX on ACT use versus standard approaches, suggesting
      that additional studies are warranted.

PMID- 23974829
TI  - Lack of referral for genetic counseling and testing in BRCA1/2 and Lynch
      syndromes: a nationwide study based on 240,134 consultations and 134,652 genetic
      tests.
AB  - Based on nationwide data from the French national cancer institute (INCa), we
      analyzed the evolution of cancer genetics consultations and testing over time,
      and the uptake of targeted tests in relatives of families with BRCA1/2 or MMR
      genes mutation. Genetic testing and consultations for familial high-risk
      individuals are exclusively funded and monitored by the INCa in France. All
      nationwide cancer genetics centers reported annually standardized parameters of
      activity from 2003 to 2011. The analysis included a total of 240,134
      consultations and 134,652 genetic tests enabling to identify 32,494 mutation
      carriers. Referral for hereditary breast and ovarian cancer (HBOC) or colorectal
      cancer predisposition syndromes represented 59 % (141,639) and 23.2 % (55,698)
      consultations, respectively. From 2003 to 2011, we found a dramatic and steady
      increase of tests performed for BRCA1/2 (from 2,095 to 7,393 tests/year, P <
      0.0001) but not for MMR genes (from 1,144 to 1,635/year, P = NS). The overall
      percentage of deleterious mutations identified in the probands tested was 13.8
      and 20.9 % in HBOC and Lynch syndromes, respectively. Pooled analysis for BRCA1/2
      and Lynch syndrome tests showed an inverse relationship between the percentage of
      mutation detected and the absolute number of tests performed over the time
      (overall Cochran-Armitage test for trend: P < 0.001). In families with BRCA1/2 or
      MMR identified mutations, there was an average number of 2.94 and 3.28 relatives
      performing targeted tests, respectively. This nationwide study shows a lack of
      referral and genetic testing in Lynch as compared to HBOC syndromes. Only a third
      of relatives of a proband with a predisposing mutation performed a targeted test.
      Enhanced information about benefit of genetic testing should be given to
      clinicians and patients for Lynch syndrome and relatives of a proband carrying an
      identified predisposing mutation.

PMID- 23974830
TI  - Eukaryotic translation initiation factor 4E (eIF4E) expression is associated with
      breast cancer tumor phenotype and predicts survival after anthracycline
      chemotherapy treatment.
AB  - Abnormal translation of mRNAs frequently occurring during carcinogenesis is among
      the mechanisms that can affect the expression of proteins involved in tumor
      development and progression. Eukaryotic initiation factor eIF4E is a key
      regulator of translation of many cancer-related transcripts and its expression is
      altered in various cancers and has been associated with worse survival. We
      determined the eIF4E protein levels using immunohistochemistry (IHC) in 1,233
      breast tumors on tissue microarrays. We analyzed the effects of the IHC
      expression level on tumor characteristics and patient survival, also with
      stratification by adjuvant chemotherapy treatment. In 1,085 successfully stained
      tumors, high level of eIF4E protein expression was associated with features of
      aggressive tumor phenotype, namely grade, estrogen and progesterone receptor
      negativity, HER2 receptor positivity, and high expression of p53 and Ki67, and
      with triple negative subtype (p < 0.001). High eIF4E expression was associated
      with worse breast cancer-specific survival with a hazard ratio (HR) of 1.99 (95 %
      CI 1.32-3.00, p = 0.0008) and was in a multivariate analysis an independent
      prognostic factor. High eIF4E expression was associated with worse outcome also
      after detection of distant metastasis (HR = 1.88, 95 % CI 1.20-2.94, p = 0.0060).
      In the subgroup analysis the survival effect was strongest among patients treated
      with anthracycline chemotherapy (HR = 3.34, 95 % CI 1.72-6.48, p = 0.0002),
      whereas no such effect was seen among patients who had not received anthracycline
      with significant difference in heterogeneity between the two groups (p = 0.0358).
      High expression of eIF4E is associated with adverse tumor characteristics and
      predicts poor breast cancer-specific survival. This effect is emphasized in
      patients treated with anthracycline chemotherapy. eIF4E as a treatment predictive
      factor warrants further studies.

PMID- 23974831
TI  - Overview: special focus vaccine acceptance.
AB  - At the World Economic Forum in 2010, The Gates Foundation announced the "Decade
      of Vaccines," a $10 billion commitment to increase access to existing and new
      childhood vaccines. It is estimated that this effort could save 6.4 million lives
      and avert 426 million illnesses [1, 2] Achieving these goals will require a
      significant effort among global health agencies, non-governmental organizations,
      industry and national governments to support vaccine development and ensure a
      strong infrastructure for sustainable vaccine delivery. Vaccines are one of the
      most important public health achievements in history, resulting in significant
      decreases in the prevalence of many childhood diseases. However, persistent
      disparities exist in the adoption of new vaccines and sustained vaccination rates
      in both developed and developing countries. Decreasing vaccination rates in some
      communities have resulted in outbreaks of vaccine-preventable diseases.
      Disparities may be due to vaccine supply, poor infrastructure, or low
      prioritization of vaccines for public health spending. However, another crucial
      contributor to the success of vaccination programs is vaccine acceptance. 

PMID- 23974832
TI  - Questionnaire for a biotech: NovaDigm Therapeutics.

PMID- 23974834
TI  - Human Vaccines & Immunotherapeutics. Letter from the editor.

PMID- 23974835
TI  - Osteolytic lesions of the calcaneus: results from a multicentre study.
AB  - PURPOSE: Tumours of the calcaneus are exceedingly rare and the correct diagnosis
      is often missed. X-rays are the standard clinical examination tool and therefore
      we wanted to discover whether X-rays alone were a sufficient diagnostic tool for
      these tumours. Diard's classification was applied to define whether different
      types of lesions were characteristically distributed in the bone and in addition
      we analysed whether type and/or duration of symptoms were possible indicators of
      malignancy. METHODS: Ninety-two patients' files (59 men and 33 women) were
      retrospectively reviewed. Seventy-five patients with a mean age at surgery of 28
      years (range five to 78) were surgically treated. Parameters analysed were sex,
      age at surgery, side, type and duration of symptoms, tentative diagnosis, biopsy
      prior to surgery, operative procedure, recurrence rate, revision and localisation
      of the lesion according to Diard. For each lesion the first documented
      radiological diagnosis and-in cases of malignancy-Enneking's classification was
      applied. RESULTS: Discrepancies between the radiological and definitive
      histological diagnosis occurred in 38 (41 %) of 92 cases. In eight (osteosarcoma
      n = 5, Ewing's sarcoma n = 2, metastases n = 1) of 17 malignant cases
      radiological examination initially gave no evidence of malignancy, resulting in
      an unplanned excision ("whoops procedure") in three cases of osteosarcoma.
      Applying Diard's system trabecular area 6 (radiolucent area) was highly affected
      in 64 (80 %) of 80 investigated plain X-rays, whereas areas 1 and 5 were affected
      in nine (11 %) and 16 (20 %) cases only. CONCLUSIONS: In each case of an
      osteolytic lesion of the calcaneus a malignant tumour must be ruled out, and thus
      preoperative plain X-rays in two planes alone are not sufficient and should
      therefore be followed by magnetic resonance imaging. Applying the Diard system
      different types of lesions are not characteristically distributed in the bone.
      Increasing pain for more than ten days without previous trauma should always
      justify further examinations.

PMID- 23974836
TI  - Primary lymphoma of bone: outcome and role of surgery.
AB  - PURPOSE: Primary bone lymphoma is a rare disease. Little is reported about
      surgical procedures in these patients. We evaluated a single-centre consecutive
      series of 21 patients for results, prognostic factors and surgical treatment.
      METHODS: Patient ages ranged from 19 to 82 years. The most frequently affected
      site was the spine (six cases), followed by the ileum, femur and mandible (three
      cases each). Four patients were treated with chemotherapy and 17 with
      chemotherapy and radiation therapy. Six patients were affected by a pathological
      fracture. Surgery was performed in four patients (19%), in two cases before
      chemotherapy, in one case during chemotherapy and in one case after chemotherapy
      and radiotherapy. Five patients died within the range of three to 36 months after
      diagnosis. Average follow-up of the remaining patients was 62.8 (19-145) months.
      RESULTS: Overall survival was 74.2% at five years. The only positive prognostic
      factor was complete remission after chemotherapy. A trend for better survival was
      present for International Prognostic Index (IPI) score (P = 0.051), under 40
      years of age (P = 0.10) and abnormal lactate dehydrogenase (LDH) values (P =
      0.10), but it did not reach statistical significance. CONCLUSIONS: Surgical
      treatment should be aimed at restoring function and eliminating pain while
      minimising delays in the chemotherapy schedule. When feasible, postponing surgery
      until after chemotherapy is advisable.

PMID- 23974837
TI  - Accelerated polyethylene wear and early failure of the uncemented Reflection
      acetabular component: a ten to fifteen-year follow-up study.
AB  - PURPOSE: The Reflection(r) second-generation uncemented acetabular component was
      designed to address increased rates of failure observed with the early acetabular
      designs. However, the reported survivorship of this acetabular component has been
      conflicting. The aim of this study was to describe the ten to 15-year
      survivorship and polyethylene wear rate for the uncemented Reflection(r)
      acetabular component performed as part of a primary total hip replacement.
      METHODS: One hundred and four consecutive Reflection(r) uncemented acetabular
      components in 97 patients were identified from a prospective arthroplasty
      database with a minimum of ten years of follow-up. No patient was lost to follow
      up. Mean cohort age was 59.1 years. RESULTS: There were 24 revisions of the
      acetabular component. The all-cause survival rate at ten years was 77.2% [95%
      confidence interval (CI) 73.9-80.5]. Mean linear wear was 0.20 mm [standard
      deviation (SD) 0.08] per year and the volumetric wear was 106.2 mm(3) per year.
      At final follow-up, more than half the patients had osteolysis identified around
      the femoral component. The mean Oxford Hip Score was 35.6 (SD 9.8) at a mean
      follow-up of 11.9 years, with six (11.1%) excellent, 26 (48.1%) good, 17 (31.5%)
      fair and five (9.3%) poor outcomes. Despite the fact that more than a third had a
      fair or poor outcome, only four (7.4%) were not satisfied with their hip.
      CONCLUSIONS: Due to the high rate of relatively asymptomatic polyethylene wear
      and osteolysis associated with this acetabular component, in our department, we
      now review all surviving patients both clinically and radiographically on an
      annual basis.

PMID- 23974838
TI  - Relationship between patient-based outcome score and conventional objective
      outcome scales in post-operative total knee arthroplasty patients.
AB  - PURPOSE: Evaluations for knee osteoarthritis (OA) or post-operative total knee
      arthroplasty (TKA) have mainly been assessed by objective scales. Though the Knee
      injury and Osteoarthritis Outcome Score (KOOS) is attracting attention as a
      patient-based outcome score, the relationship with conventional objective scales
      after TKA remains controversial. The purpose of this study was to investigate the
      relationship between KOOS and conventional objective scales and evaluate the
      features of patient-based outcome scores. METHODS: Subjects were 130 post
      operative patients involving 186 knees treated with TKA. Their mean age was 74.0
      +/- 8.0 years, and the follow-up period was 43 months. Japanese Orthopaedic
      Association (JOA) score, original Knee Society Score (KSS) and surgeon's
      satisfaction score were scored as conventional objective scales besides KOOS.
      Spearman's correlation coefficient was estimated between these scales.
      Comparisons between OA and rheumatoid arthritis (RA) as well as primary and
      revision surgery were performed by the Mann-Whitney U test. RESULTS: There were
      strong correlations between KOOS activities of daily living (ADL) and JOA score
      (r = 0.806), KSS function score (r = 0.803) and between KOOS pain and KSS knee
      score (r = 0.689). However, there was a poor correlation between KOOS and
      surgeon's satisfaction score (r = 0.188-0.321). TKA for RA showed poorer results
      only in KOOS pain (p = 0.003), and revision surgery showed poorer results in KSS
      function, KOOS symptoms and KOOS quality of life (QOL). CONCLUSIONS: This study
      suggested that conventional objective scales reflected mainly ADL disturbances in
      post-operative TKA patients. Furthermore, patient-based outcome scores made it
      possible to evaluate and detect a minute change of knee pain and QOL in TKA
      patients. The Japanese KOOS was a useful tool to evaluate conditions after TKA.

PMID- 23974839
TI  - Safety of a novel high tibial osteotomy locked plate fixation for immediate full
      weight-bearing: a case-control study.
AB  - PURPOSE: The safety and efficacy of the novel Limmed(r) system (locked plate
      fixation) for immediate full weight-bearing after medial opening wedge high
      tibial osteotomy (HTO) were evaluated in patients with symptomatic varus
      gonarthrosis. METHODS: A case series of 85 consecutive osteotomies performed with
      Limmed(r) locked plate fixation for medial opening wedge HTO was compared to a
      historical matched case-control series of 85 HTOs (85 patients) performed using
      the same implant without locked screws. Subjects were observed at seven and 15
      days and three, six and 12 months after surgery. Endpoints for evaluation
      included the reporting of adverse events, weight-bearing status without pain,
      radiographic evidence of bony union and changes in correction angle during
      healing. RESULTS: Statistically significant differences were seen between groups
      in terms of safety (thrombophlebitis), time to weight-bearing, radiographic union
      and radiographic stability between the two groups. Patients of the Limmed(r)
      group reported less thrombophlebitis (one versus nine), outcome with shorter time
      for full weight-bearing (average 45 days difference, p = 0.01) and a shorter time
      for union (average four weeks difference). At the one-year follow-up the post
      operative hip-knee-ankle angle was 4.2 degrees  of valgus in the Limmed(r) group
      and 2 degrees  of valgus in the control group. The adjusted mean difference of
      2.2 degrees  was significant (p = 0.02) and related to loss of correction during
      healing in the control group with difference in implant stability. The severity
      of pain, knee score and walking ability improved in both groups with a
      significant difference before the third month (quicker for Limmed(r) group),
      while at the most recent follow-up only the difference for mobility in flexion
      was significant. CONCLUSIONS: The Limmed(r) medial opening wedge HTO system
      represents a novel method of achieving a reliable correction while producing a
      stable fixation allowing satisfactory stability and bone healing with immediate
      full weight-bearing.

PMID- 23974840
TI  - Flexor digitorum longus transfer and medial displacement calcaneal osteotomy for
      the treatment of stage II posterior tibial tendon dysfunction: kinematic and
      functional results of fifty one feet.
AB  - PURPOSE: Stage II posterior tibial tendon dysfunction (PTTD) can be treated by
      flexor digitorum longus (FDL) tendon transfer and medial displacement calcaneal
      osteotomy (MDCO). Numerous authors have studied the clinical and radiographic
      results of this procedure. However, little is known about the kinematic changes.
      Therefore, the purpose of this study was to assess plantar-pressure distribution
      in these patients. METHODS: Seventy-three patients with PTTD stage II underwent
      FDL tendon transfer and MDCO. Plantar pressure distribution and American
      Orthopaedic Foot and Ankle Society (AOFAS) score were assessed 48 months after
      surgery. Pedobarographic parameters included lateral and medial force index of
      the gait line, peak pressure (PP), maximum force (MF), contact area (CA), contact
      time (CT) and force-time integral (FTI). RESULTS: In the lesser-toe region, PP,
      MF, CT, FTI and CA were reduced and MF in the forefoot region was increased.
      These changes were statistically significant. We found statistically significant
      correlations between AOFAS score and loading parameters of the medial midfoot.
      CONCLUSIONS: Study results reveal that FDL tendon transfer and MDCO leads to
      impaired function of the lesser toes during the stance phase. However, there
      seems to be a compensating increased load in the forefoot region.

PMID- 23974841
TI  - Evolution of vitreomacular detachment in healthy subjects.
AB  - IMPORTANCE: Development of posterior vitreous detachment (PVD) plays an important
      role in vitreomacular diseases. Spectral-domain optical coherence tomography (SD
      OCT) with noise reduction can visualize a posterior precortical vitreous pocket
      (PPVP) and classify PVD stages according to the state of the posterior wall of
      the PPVP. OBJECTIVE: To describe the role of the PPVP in early-stage PVDs in
      healthy individuals. DESIGN, SETTING, AND PARTICIPANTS: We performed
      biomicroscopy and SD-OCT in the right eyes of 368 healthy volunteers (188 males
      and 180 females; mean [SD] age, 57.1 [19.4] years; range, 12-89 years). RESULTS:
      The condition of the posterior wall of the PPVP was classified into stages
      according to the biomicroscopic findings and SD-OCT images: stage 0, no PVD with
      PPVP (134 eyes; mean [SD] subject age, 38.7 [16.5] years; range, 12-76 years);
      stage 1, paramacular PVD with PPVP (47 eyes; mean age, 55.2 [10.3] years; range,
      36-77 years); stage 2, perifoveal PVD with PPVP (27 eyes; mean age, 62.0 [8.7]
      years; range, 46-81 years); stage 3, vitreofoveal separation with persistent
      attachment to the optic disc (19 eyes; mean age, 65.8 [6.2] years; range, 55-80
      years; stage 3a, vitreofoveal separation with an intact posterior wall of the
      PPVP in 12 eyes; stage 3b, vitreofoveal separation with a defect in the posterior
      wall of the PPVP in 7 eyes; and stage 4, complete PVD (141 eyes; mean age, 73.2
      [8.3] years; range, 48-89 years). MAIN OUTCOMES AND MEASURES: Ages in each PVD
      stage. CONCLUSIONS AND RELEVANCE: The posterior wall of the PPVP initially
      detaches at the paramacular area and extends to the perifoveal area, which
      results in a perifoveal PVD. A vitreofoveal detachment may develop with or
      without a defect in the PPVP. When the vitreous detaches from the optic disc, a
      complete PVD develops. An anatomical feature of the PPVP may play a role in the
      development of a perifoveal PVD.

PMID- 23974842
TI  - The association of ultraviolet radiation-B (305 nm), season of diagnosis, and
      latitude on the survival outcome of prostate cancer in the high UV environment of
      Australia.
AB  - BACKGROUND: Positive associations between sun exposure and cancer survival have
      been observed in regions of high latitudes, where ambient solar ultraviolet (SUV)
      radiation is generally low. PURPOSE: We examined the effects of ambient
      ultraviolet-B radiation (UVB) at time of diagnosis, season of diagnosis and
      latitude of residence on survival outcome from prostate cancer. METHOD:
      Regression models for relative survival were used to estimate relative excess
      risks (RER) of death after diagnosis of prostate cancer from cancer registries in
      Eastern Australia (Queensland, New South Wales, Victoria and Tasmania). RESULTS:
      Relative excess risks was increased with diagnosis in summer (RER = 1.20; 95 % CI
      1.14-1.26) relative to winter, high ambient UVB at the time of diagnosis (>60
      mW/m(2); RER = 1.10; 95 % CI 1.05-1.15) relative to low SUV (<30 mW/m(2)), and
      with residence in high latitudes (35 degrees S-43 degrees S; RER = 1.20; 95 % CI
      1.14-1.26) relative to low latitudes (9 degrees S-29.9 degrees S). RER was
      highest for summer diagnosis in all three latitude bands, after adjusting for
      age, follow-up period, and socioeconomic status. CONCLUSION: The contradictory
      outcome from season and latitude suggests that their use as surrogates for UV
      warrants validation. Our data suggest that high ambient solar ultraviolet
      radiation at the time of diagnosis of prostate cancer increases the risk of dying
      from this cancer.

PMID- 23974843
TI  - Suicide prevention in the WHO Mental Health Gap Action Programme (mhGAP).

PMID- 23974846
TI  - Thermal perceptions and skin temperatures during continuous and intermittent
      ventilation of the torso throughout and after exercise in the heat.
AB  - OBJECTIVE: This study tested the hypothesis that intermittent cooling in air
      perfused vests (APV) will not only maintain thermal balance but, due to cyclical
      activations of cutaneous thermoreceptors, also enhance thermal perceptions.
      METHOD: Ten physically active males completed four conditions where they
      exercised (walking: 5 km h(-1), 2 % gradient) in a hot environment (~34.0 
      degrees C, 50 % RH) for 72 min, followed by a 33-min period of rest. They wore an
      APV throughout. The four conditions differed in respect to the profile of ambient
      air that was perfused through the APV: continuous perfusion (CP); intermittent
      perfusion of 6 min ON/OFF periods (IPonoff); a steady increase and decrease in
      flow rate in equal increments (IPramp); and an initial step-increase in the flow
      rate followed by an incremental decrease to zero flow rate (IPtriang). Whole body
      and torso thermal comfort (TC, TTC), whole body and torso temperature sensation
      (TS, TTS), whole body and torso skin temperature ([Formula: see text], [Formula:
      see text]), local relative humidity ([Formula: see text]) and rectal temperature
      (T re) were measured. RESULTS: There were no significant differences in T re,
      absolute whole body and local [Formula: see text], TC, TTC and TS between the
      cooling profiles. However, TTS was cooler in CP and IPramp than IPonoff and
      IPtriang. Even though intermittent cooling did not significantly enhance thermal
      perceptions in CP, a trend existed for TC (P = 0.063) to become less favourable
      over time. CONCLUSION: To reduce the power consumption and extend the battery
      life of an APV, it is recommended that an intermittent cooling profile should be
      adopted.

PMID- 23974847
TI  - External muscle heating during warm-up does not provide added performance benefit
      above external heating in the recovery period alone.
AB  - PURPOSE: Having previously shown the use of passive external heating between warm
      up completion and sprint cycling to have had a positive effect on muscle
      temperature (T m) and maximal sprint performance, we sought to determine whether
      adding passive heating during active warm up was of further benefit. METHODS: Ten
      trained male cyclists completed a standardised 15 min sprint based warm-up on a
      cycle ergometer, followed by 30 min passive recovery before completing a 30 s
      maximal sprint test. Warm up was completed either with or without additional
      external passive heating. During recovery, external passive leg heating was used
      in both standard warm-up (CONHOT) and heated warm-up (HOTHOT) conditions, for
      control, a standard tracksuit was worn (CON). RESULTS: T m declined exponentially
      during CON, CONHOT and HOTHOT reduced the exponential decline during recovery.
      Peak (11.1 %, 1561 +/- 258 W and 1542 +/- 223 W), relative (10.6 % 21.0 +/- 2.2 W
      kg(-1) and 20.9 +/- 1.8 W kg(-1)) and mean (4.1 %, 734 +/- 126 W and 729 +/- 125
      W) power were all improved with CONHOT and HOTHOT, respectively compared to CON
      (1,397 +/- 239 W; 18.9 +/- 3.0 W kg(-1) and 701 +/- 109 W). There was no
      additional benefit of HOTHOT on T m or sprint performance compared to CONHOT.
      CONCLUSION: External heating during an active warm up does not provide additional
      physiological or performance benefit. As noted previously, external heating is
      capable of reducing the rate of decline in T m after an active warm-up, improving
      subsequent sprint cycling performance.

PMID- 23974849
TI  - [Where did the rollmops skewer come from?].

PMID- 23974848
TI  - Alterations in coagulatory and fibrinolytic systems following an ultra-marathon.
AB  - PURPOSE: The aim of this study was to examine coagulatory and fibrinolytic
      responses to the Western States Endurance Run (WSER, June 23 to 24, 2012). The
      WSER is a 161-km (100 mile) trail foot race through the Sierra Nevada Mountains
      that involves 6,030 m of climb and 7,001 m of descent. METHODS: We examined 12
      men and 4 women [mean (95 % CI), age 44.6 years (38.7-50.6)] who completed the
      race (24.64 h; range 16.89-29.46). Blood samples were collected the morning
      before the race, immediately post-race, and 1 (D1) and 2 (D2) days post-race
      (corresponding to 51-54 h and 75-78 h from the start of the race, respectively).
      Hypercoagulable state was characterized by prothrombin fragment 1+2 (PTF 1+2) and
      thrombin-antithrombin complex (TAT). Fibrinolytic state was assessed by
      plasminogen activator inhibitor antigen (PAI-1 Ag), tissue plasminogen activator
      antigen (tPA Ag), and D-Dimer. Muscle damage was assessed by serum creatine
      kinase (CK) and myoglobin concentrations. RESULTS: Significant (P <= 0.05)
      increases were observed immediately post-race for thrombin generation markers,
      PTF 1+2 (3.9-fold) and TAT (2.4-fold); markers of fibrinolysis, tPA Ag (4.0
      fold), PAI-1 Ag (4.5-fold), and D-Dimer (2.2-fold); and muscle damage markers, CK
      (154-fold) and myoglobin (114-fold). Most markers continued to be elevated at D1,
      as seen by PTF 1+2, TAT (1.5- and 1.3-fold increase at D1), and D-Dimer (2.5- and
      2.1-fold increase at D1 and D2, respectively). Additionally, PTF 1+2:tPA and
      TAT:tPA ratios, which assessed balance between coagulation and fibrinolysis, were
      slightly, but significantly increased at D1 (69 and 36 %) and D2 (19 and 31 %).
      CK and myoglobin also remained elevated at D1 (54- and 7-fold) and D2 (25- and 2
      fold) time points. CONCLUSION: The WSER produced extensive muscle damage and
      activated the coagulation and fibrinolytic systems. Since we observed a slight
      imbalance response between the two systems, a limited potential for thrombotic
      episodes is apparent in these highly trained athletes.

PMID- 23974850
TI  - [A dramatic cause of back and shoulder pain].

PMID- 23974851
TI  - [Quality offensive in organ acquisition of Bavarian transplantation centers].

PMID- 23974853
TI  - Reduction in health service use for whiplash injury after motor vehicle accidents
      in 2000-2009: results from a defined population.
AB  - OBJECTIVE: To establish trends in whiplash-related health service use and cost in
      Victoria, Australia. DESIGN: Administrative data analysis. SUBJECTS: Whiplash
      patients claiming Transport Accident Commission (TAC) compensation for accidents
      dating between 1 January 2000 and 31 December 2009 (n = 51,263). METHODS: Injury
      related health service use during one year following the accident was determined
      from claim payment records. The incidence of whiplash claims in Victoria was
      calculated, as were inflation-adjusted health care costs. RESULTS: In 2000-2009,
      the incidence of compensable whiplash decreased from 1.56 to 1.14 per 1,000
      person-years. Physiotherapy, pharmaceuticals, general practitioner, chiropractic,
      radiology and osteopathy sessions were the most commonly claimed services.
      General practitioner, allied health and radiology services decreased, but
      analgesic use increased. Per person-years in the population, whiplash-related
      medical expenses were 71% greater for women than men. Overall, population burden
      decreased by 38%; the decline was most pronounced in persons aged 18-24 (54%
      decrease) and least pronounced in those aged >= 55 (23% decrease). CONCLUSION:
      The population-based health service cost of whiplash decreased between 2000 and
      2009. The overall reduction was related to a decrease in incidence and a
      reduction in service use per whiplash claim.

PMID- 23974852
TI  - Berberine suppresses gero-conversion from cell cycle arrest to senescence.
AB  - Berberine (BRB), a natural alkaloid, has a long history of medicinal use in both
      Ayurvedic and old Chinese medicine. Recently, available as a dietary supplement,
      Berberine is reported to have application in treatment of variety diseases.
      Previously we observed that BRB inhibited mTOR/S6 signaling concurrently with
      reduction of the level of endogenous oxidants and constitutive DNA damage
      response. We currently tested whether Berberine can affect premature, stress
      induced cellular senescence caused by mitoxantrone. The depth of senescence was
      quantitatively measured by morphometric parameters, senescence-associated beta
      galactosidase, induction of p21WAF1, replication stress (gammaH2AX expression),
      and mTOR signaling; the latter revealed by ribosomal S6 protein (rpS6)
      phosphorylation. All these markers of senescence were distinctly diminished, in a
      concentration-dependent manner, by Berberine. In view of the evidence that BRB
      localizes in mitochondria, inhibits respiratory electron chain and activates
      AMPK, the observed attenuation of the replication stress-induced cellular
      senescence most likely is mediated by AMPK that leads to inhibition of mTOR
      signaling. In support of this mechanism is the observation that rhodamine123, the
      cationic probe targeting mitochondrial electron chain, also suppressed rpS6
      phosphorylation. The present findings reveal that: (a) in cells induced to
      senescence BRB exhibits gero-suppressive properties by means of mTOR/S6
      inhibition; (b) in parallel, BRB reduces the level of constitutive DNA damage
      response, previously shown to report oxidative DNA damage by endogenous ROS; (c)
      there appears to a causal linkage between the (a) and (b) activities; (d) the in
      vitro model of premature stress-induced senescence can be used to assess
      effectiveness of potential gero-suppressive agents targeting mTOR/S6 and ROS
      signaling; (e) since most of the reported beneficial effects of BRB are in age
      relate diseases, it is likely that gero-suppression is the primary activity of
      this traditional medicine. 

PMID- 23974854
TI  - Responses of protocerebral neurons in Manduca sexta to sex-pheromone mixtures.
AB  - Male Manduca sexta moths are attracted to a mixture of two components of the
      female's sex pheromone at the natural concentration ratio. Deviation from this
      ratio results in reduced attraction. Projection neurons innervating prominent
      male-specific glomeruli in the male's antennal lobe produce maximal synchronized
      spiking activity in response to synthetic mixtures of the two components
      centering around the natural ratio, suggesting that behaviorally effective
      mixture ratios are encoded by synchronous neuronal activity. We investigated the
      physiological activity and morphology of downstream protocerebral neurons that
      responded to antennal stimulation with single pheromone components and their
      mixtures at various concentration ratios. Among the tested neurons, only a few
      gave stronger responses to the mixture at the natural ratio whereas most did not
      distinguish among the mixtures that were tested. We also found that the
      population response distinguished among the two pheromone components and their
      mixtures, prior to the peak population response. This observation is consistent
      with our previous finding that synchronous firing of antennal-lobe projection
      neurons reaches its maximum before the firing rate reaches its peak. Moreover,
      the response patterns of protocerebral neurons are diverse, suggesting that the
      representation of olfactory stimuli at the level of protocerebrum is complex. 

PMID- 23974855
TI  - Guidance by odors in honeybee navigation.
AB  - Animal navigation is guided by multiple sensory cues. Here, we ask whether and
      how olfactory stimuli emanating from places other than the trained feeding site
      redirect the flight paths of honeybees. The flight trajectories of individual
      bees were registered using harmonic radar tracking. Sensory cues (compass
      direction, distance, visual cues en route and close to the feeding site)
      associated with the trained flight route dominated wayfinding, but a learned
      odorant carried by air flow induced excursions into the wind. These redirections
      were largely restricted to rather small deviations from the trained route (<60
      degrees , <200 m) and occurred only if the animal did not receive the trained
      odorant stimulus at the trained feeding site. Under certain conditions, larger
      excursions were observed. These findings are discussed in the context of odor
      guidance of honeybees over longer distances (>300 m from the hive). 

PMID- 23974857
TI  - Inclinometer-based measures of standing posture in older adults with low bone
      mass are reliable and associated with self-reported, but not performance-based,
      physical function.
AB  - The association between posture and physical function during daily activities in
      people at risk for osteoporotic fracture is not clear. We report the reliability
      of measuring posture using the digital inclinometer and how these measures relate
      to performance-based and self-reported physical function. INTRODUCTION: This
      study aims to determine the reliability of a simple clinical method for assessing
      spine curvatures in people with low bone mass and the association between spine
      curvature measures and pain, physical function (mobility/activities of daily
      living (ADL)) and quality of life. METHODS: One rater assessed 36 high
      functioning adults, aged 52-82 years, attending an outpatient osteoporosis
      clinic. A digital inclinometer was used to measure lumbosacral angle (S), lumbar
      standing posture (L), and thoracic standing posture (T) and ADL performance was
      assessed using the short form of the Safe Functional Motion test (SFM-6), on two
      occasions approximately 8.7 days apart. Participants reported average pain
      intensity over the past week and completed the Timed Up and Go test (TUGT) and
      the mini-Osteoporosis Quality of Life questionnaire (mini-OQLQ). Acceptable
      reliability was determined using the intraclass correlation coefficient (ICC).
      Associations were determined using Pearson's correlation coefficients (r) (and
      Spearman's rho (r s), for non-normal data). RESULTS: ICC (95 % CI) for S, L, and
      T = 0.91 (0.82, 0.95), 0.90 (0.82, 0.95), and 0.91 (0.84, 0.95), respectively,
      for test-retest reliability. Thoracic standing posture was associated with the
      ADL domain of the mini-OQLQ (r s = -0.39) and the TUGT (r = 0.42). Standing
      posture was not related to pain or total SFM-6 score. CONCLUSIONS: Digital
      inclinometer measures provide a quick highly reliable, valid, direct assessment
      of kyphosis. Use of these measures in the clinical setting is expected to
      facilitate identification and effective management of postural impairments (e.g.,
      trunk extensor muscle weakness, vertebral fracture) associated with osteoporosis.

PMID- 23974856
TI  - Mild morphometric vertebral fractures predict vertebral fractures but not non
      vertebral fractures.
AB  - In this meta-analysis of the control arms of four phase 3 trials, mild vertebral
      fractures were a significant risk factor for future vertebral fractures but not
      for non-vertebral fracture. INTRODUCTION: A prior vertebral fracture is a risk
      factor for future fracture that is commonly used as an eligibility criterion for
      treatment and in the assessment of fracture probability. The aim of this study
      was to determine the prognostic significance of a morphometric fracture according
      to the severity of fracture. METHODS: We examined the control (placebo) treated
      arms of four phase 3 trials. Vertebral fracture status was graded at baseline in
      7,623 women, and fracture outcomes were documented over the subsequent 20,000
      patient-years. Fracture outcomes were characterised as a further vertebral
      fracture, a non-vertebral fracture or a clinical fracture (non-vertebral plus
      clinical vertebral fracture). The relative risk of fracture was computed from the
      merged beta coefficients of each trial weighted according to the variance.
      RESULTS: Mild vertebral fractures were a significant risk factor for vertebral
      fractures [risk ratio (RR) = 2.17; 95% CI = 1.70-2.76] but were not associated
      with an increased risk of non-vertebral fractures (RR = 1.08; 95% CI = 0.86
      1.36). Moderate/severe vertebral fractures were associated with a high risk of
      vertebral fractures (RR = 4.23; 95% CI = 3.58-5.00) and a moderate though
      significant increase in non-vertebral fracture risk (RR = 1.64; 95% CI = 1.38
      1.94). CONCLUSIONS: Prior moderate/severe morphometric vertebral fractures are a
      strong and significant risk factor for future fracture. The presence of a mild
      vertebral fracture is of no significant prognostic value for non-vertebral
      fractures. These findings should temper the use of morphometric fractures in the
      assessment of risk and the design of phase 3 studies.

PMID- 23974858
TI  - Reference values of osteocalcin and procollagen type I N-propeptide plasma levels
      in a healthy Central European population aged 0-18 years.
AB  - The aim of this study was to assess the relationships between both a marker of
      bone formation and a marker of bone turnover and age, sex, and pubertal stage in
      a group (n = 439) of healthy children and adolescents. These reference data
      should be instrumental in interpretation of results. INTRODUCTION: The skeletal
      system has high metabolic activity. In children, bone markers may be useful in
      diagnostics and treatment management of skeletal diseases but there could be
      difficulties with interpretation of results. Compared with adults, children have
      elevated bone marker levels due to high skeletal growth velocity and rapid bone
      turnover. Thus, valid age- and sex-specific reference data should be obtained for
      each pediatric population living in a particular climate and with a similar
      lifestyle. The aim of this study was to assess the relationships between both a
      marker of bone formation (procollagen type I N-terminal propeptide [PINP]) and a
      marker of bone turnover (osteocalcin [OC]) and age, sex, and pubertal stage in a
      group of healthy children and adolescents. METHODS: Four hundred thirty-nine
      healthy Caucasian children participated. Their height, weight, and pubertal stage
      were recorded. Fasting PINP and OC were measured using a morning blood sample.
      RESULTS: The highest levels of PINP were observed during the first year of life.
      There is no OC postnatal peak, but levels are higher than the adult reference
      interval throughout childhood. OC peaks with the pubertal growth spurt at second
      third Tanner stage of breast development in girls and at second-third Tanner
      stage of genital development in boys. PINP peaks during second-third Tanner stage
      of breast development in girls and at third Tanner stage of genital development
      in boys. CONCLUSION: This study provides reference data for OC and PINP in
      healthy Caucasian children from a Central European population.

PMID- 23974859
TI  - Association of volumetric bone mineral density with abdominal aortic
      calcification in African ancestry men.
AB  - SUMMARY: We tested for association between cortical and trabecular volumetric
      bone mineral density (vBMD) with abdominal aortic calcification (AAC) prevalence
      in 278 Afro-Caribbean men. AAC was present in 68.3 % of the men. Greater
      cortical, but not trabecular, vBMD was associated with significantly decreased
      odds of AAC independent of traditional risk factors. INTRODUCTION: The aim of
      this study is to assess the prevalence and correlates of AAC in a sample of 278
      Afro-Caribbean men (mean age 56) and to test for a largely unexplored association
      between cortical and trabecular vBMD with AAC prevalence. METHODS: Men were
      recruited consecutively as part of an ongoing prospective cohort study of body
      composition in men aged 40+. For this analysis, AAC was assessed by computed
      tomography of the abdomen from L3 to S1. Aortic calcium was scored using the
      Agatston method, and prevalence was defined as a score >=10 to rule out false
      positives. Men also had BMD assessed using peripheral quantitative computed
      tomography at 4 % (trabecular vBMD) and 33 % (cortical vBMD) of the radius and
      tibia. RESULTS: Abdominal aortic calcification was present in 68.3 % of the men.
      Significant independent predictors of AAC prevalence were increased age,
      increased BMI, hypertension, and current smoking. Age was the strongest
      predictor, with each SD (7.8 year) increase in age conferring 2.7 times increased
      odds of having AAC (P < 0.0001). A one SD greater cortical, but not trabecular,
      vBMD was associated with a significant decreased odds of AAC prevalence
      independent of other traditional risk factors (OR 0.65; 95 % CI 0.45-0.92).
      CONCLUSIONS: Cortical vBMD is inversely associated with AAC presence. This
      finding suggests that there may be shared physiology between cortical bone
      compartment remodeling and vascular calcification.

PMID- 23974860
TI  - Prevalence and progression of radiographic ossification of the posterior
      longitudinal ligament and associated factors in the Japanese population: a 3-year
      follow-up of the ROAD study.
AB  - SUMMARY: The prevalence of radiographic cervical ossification of the posterior
      longitudinal ligament (OPLL) in 1,562 Japanese from a population-based cohort was
      1.9 %. The presence of OPLL showed a significant association with the femoral
      neck bone mineral density (BMD), presence of diffuse idiopathic skeletal
      hyperostosis (DISH) and plasma pentosidine levels. Only one new case of
      radiographic OPLL was detected, but OPLL progressed in all affected subjects.
      INTRODUCTION: The purpose of this study was to clarify the prevalence and
      progression of radiographic OPLL and the associated factors, using the population
      based cohort Research on Osteoarthritis/osteoporosis Against Disability (ROAD).
      METHODS: In the ROAD study, 1,690 participants underwent X-ray examination of the
      entire spine and both knees. Radiographic OPLL, lumbar spondylosis, knee
      osteoarthritis and DISH were diagnosed by a single, well-experienced orthopaedic
      surgeon. An interviewer-administered questionnaire and tests for anthropometric
      measurements were administered, and the BMDs of the lumbar spine and proximal
      femur were determined. A new OPLL case was considered if heterotopic ossification
      in the posterior longitudinal ligament was absent at baseline but present during
      follow-up. Progression was defined as an increase in the maximum length or width
      of the ossification at follow-up over that at baseline. RESULTS: Radiographic
      OPLL was detected in 30 (17 men, 13 women) of 1,562 individuals who underwent X
      ray examination of the cervical spine (prevalence = 1.9 %). Its prevalence was
      significantly higher in men than in women (p = 0.007), but no association with
      age was observed. In a logistic regression analysis, OPLL showed a significant
      association with the femoral neck BMD, presence of DISH and plasma pentosidine
      levels. Only one new case of radiographic OPLL was detected, but OPLL progressed
      in all affected subjects. CONCLUSION: This population-based study clarified the
      prevalence of radiographic OPLL in the Japanese population as well as its
      progression. OPLL showed significant association with plasma pentosidine levels,
      BMD and DISH.

PMID- 23974861
TI  - Osteoanabolic effect of alendronate and zoledronate on bone marrow stromal cells
      (BMSCs) isolated from aged female osteoporotic patients and its implications for
      their mode of action in the treatment of age-related bone loss.
AB  - SUMMARY: In the present study, we evaluated the potential for
      aminobisphosphonates to enhance the development of bone-forming osteoblasts from
      progenitor cells isolated from aged female osteoporotic patients. The
      aminobisphosphonates tested significantly enhanced osteoblast formation and thus
      lend further insights into their possible mode of action in the treatment of
      osteoporosis. INTRODUCTION: The primary aim of this study was to evaluate the
      influence of aminobisphosphonates on the osteogenesis of human bone marrow
      stromal cells (hBMSCs) and mineralization of differentiating bone-forming cells
      isolated from osteoporotic patients. METHODS: The influence of
      aminobisphosphonate treatment on hBMSC osteogenesis was assessed by the
      quantitative measurement of alkaline phosphatase (ALP) activity, in addition to
      quantitative reverse transcription polymerase chain reaction and Western blot
      analysis of known osteogenic markers. Mineralized matrix formation by hBMSC
      derived osteoblasts was visualized and quantified using Alizarin red staining.
      RESULTS: hBMSC cultures treated with osteogenic medium supplemented with
      zoledronate demonstrated a significant increase in Alizarin red staining after 3
      weeks as compared to cells cultured in osteogenic medium alone. Similarly,
      cultures of differentiating hBMSCs isolated from patients receiving alendronate
      treatment also demonstrated an increased propensity for mineralization, even in
      the absence of further in vitro stimulation by zoledronate. The stimulatory
      effects of aminobisphosphonate treatment on hBMSC-derived osteoblast-mediated
      mineralization were independent of any alterations in ALP activity, although
      significant decreases in the expression levels of osteopontin (SPP1) were evident
      in hBMSCs following exposure to aminobisphosphonates. Further analysis including
      Western blotting and loss-of-function studies revealed osteopontin as having a
      negative influence on the mineralization of differentiating osteoporotic bone
      forming cells. CONCLUSIONS: The results presented here demonstrate for the first
      time that aminobisphosphonate treatment of osteoporotic hBMSCs enhances their
      capacity for osteoblast formation and subsequent mineral deposition, thus
      supporting the concept of aminobisphosphonates as having an osteoanabolic effect
      in osteoporosis.

PMID- 23974862
TI  - Comparison of open and laparoscopic preperitoneal repair of groin hernia.
AB  - BACKGROUND: Compared with laparoscopic groin herniorrhaphy, the open procedure
      used in most former studies was Lichtenstein repair. However, unlike the totally
      extraperitoneal (TEP) or transabdominal preperitoneal (TAPP) laparoscopic
      techniques, Lichtenstein procedure is a premuscular but not preperitoneal repair.
      This retrospective study compared the outcomes between laparoscopic preperitoneal
      and open preperitoneal procedure-modified Kugel (MK) herniorrhaphy. METHODS:
      Groin hernia patients older than 18 years who underwent open MK or laparoscopic
      preperitoneal herniorrhaphy in our hospitals between January 2008 and December
      2010 were enrolled. Baseline characteristics, recurrence, and intraoperative,
      short-term, and long-term postoperative complications were recorded. RESULTS:
      Among the 1,760 included patients (530 open and 1,230 laparoscopic), 96.08%
      completed the follow-up (24-60 months). The patients in the open group were older
      than laparoscopic group (p < 0.001). More bilateral (91.45%) and recurrent
      (82.12%) hernia patients underwent laparoscopic procedures (p < 0.001 and p =
      0.004, respectively). The overall recurrence rate was 0.71%, with no significant
      difference between the two approaches (p = 0.227). The overall complication rate
      was lower for the laparoscopic than the open approach (14.47 vs. 19.25%, p =
      0.012), whereas the rates of life-threatening complications were similar (1.51
      vs. 0.98%, p = 0.332). The laparoscopic group had significantly lower incidence
      rates of wound infection and chronic pain (p = 0.016 and p < 0.001,
      respectively), shorter operative time, lower visual analogue scale scores, and
      faster recovery than the open group (p < 0.001). CONCLUSIONS: As preperitoneal
      herniorrhaphy, both MK and laparoscopic (TEP/TAPP) procedures are safe and
      effective, with low incidence rates of life-threatening complications and
      recurrence. The laparoscopic approach is superior in terms of lower incidence
      rates of infection and chronic pain, shorter operative time, and faster recovery;
      however, careful surgical procedure selection and implementation of technical
      details are required.

PMID- 23974863
TI  - ASCO 2013: from the rediscovery of old recipes to targeted oncology.

PMID- 23974864
TI  - Estrogen deficiency reduces the dentinogenic capacity of rat lower incisors.
AB  - Endogenous estrogen deficiency usually causes the systemic osteoporosis including
      the jaw bones. However, it remains unclear whether estrogen deficiency can affect
      the tooth mineralization. In this study, the classical osteoporotic rat model was
      established via the ovariectomy, which was subsequently confirmed by the
      detection of serum estradiol levels and body weights. The mineralization-related
      assays were performed to observe the potential changes in mineralized tissues of
      rat lower incisors. The clinical crown length, compressive strength,
      radiodensity, and calcium content in the ovariectomy group (OVX) were
      significantly downregulated (P < 0.01), as compared with the sham operation group
      (Sham). Histological results revealed that OVX incisors presented the thinner
      predentin structures than Sham incisors. Immunohistochemical staining and western
      blot assay further demonstrated that the odonto/osteoblast specific proteins
      (e.g., dentin sialoprotein, runt-related transcription factor 2, osterix, and
      osteocalcin) in the dentin-pulp complex of OVX incisors were significantly
      decreased in comparison with Sham counterparts. Together, estrogen deficiency
      reduces the dentinogenic capacity and calcium deposition in rat incisors,
      indicating that estrogen plays an important role in the dentinogenesis. 

PMID- 23974865
TI  - Sonoanatomy relevant for lumbar plexus block in volunteers correlated with cross
      sectional anatomic and magnetic resonance images.
AB  - BACKGROUND: Ultrasound imaging of the anatomy relevant for lumbar plexus block
      (LPB) is challenging because of its deep anatomic location and the "acoustic
      shadow" of the overlying transverse processes. A paramedian transverse scan
      (PMTS) of the lumbar paravertebral region with the ultrasound beam being
      insonated through the intertransverse space (ITS) and directed medially toward
      the intervertebral foramen (PMTS-ITS) may overcome the problem of the "acoustic
      shadow" and allow clear visualization of the anatomy relevant for LPB. This study
      assessed the feasibility of using PMTS-ITS for imaging the anatomy relevant for
      LPB in healthy volunteers. METHODS: Thirty young volunteers underwent a PMTS-ITS
      of the right lumbar paravertebral region. The sonoanatomy was defined in
      corresponding cadaver anatomic sections and magnetic resonance images. Visibility
      of the paravertebral structures in the sonograms was assessed by 4 independent
      observers using a 4-point Likert scale (0, not visible; 1, hardly visible; 2,
      well visible; 3, very well visible), and the mean total ultrasound visibility
      score (UVS; maximum score possible, 30) was determined. Overall ultrasound
      visibility was judged as good if the total UVS was greater than 20, average if it
      was 10 to 20, and poor if it was less than 10. RESULTS: Ultrasound imaging of the
      right lumbar paravertebral region at the L3-L4-L5 vertebral level was
      successfully performed through the PMTS-ITS scan window in all volunteers
      studied. The lumbar nerve root, lumbar paravertebral space, lumbar plexus, and
      the psoas compartment were delineated in 57%, 27%, 57%, and 87% of volunteers,
      respectively. Overall ultrasound visibility of the lumbar paravertebral
      structures was judged as "good" (mean [SD] total UVS, 20.4 [3]). CONCLUSIONS: A
      PMTS-ITS can be used to image the sonoanatomy relevant for LPB including the
      lumbar nerve root, lumbar paravertebral space, lumbar plexus, and the psoas
      compartment.

PMID- 23974866
TI  - Investigation of current infection-control practices for ultrasound coupling gel:
      a survey, microbiological analysis, and examination of practice patterns.
AB  - BACKGROUND AND OBJECTIVES: Ultrasound coupling gel may serve as a vector for the
      spread of bacteria and has been the causative agent for significant health care
      associated infections. The purpose of this study was to document existing
      infection-control procedures and level of contamination present within nonsterile
      ultrasound gel from several clinical departments at a single institution. A
      second purpose was to examine the effectiveness of clinician education and
      manufacturer-based ultrasound additives on ultrasound gel contamination and in
      vitro bacterial proliferation, respectively. METHODS: Compliance with Health
      Canada recommended infection-control policies were determined by survey.
      Contamination of in-use ultrasound gel bottles was determined by inspecting
      cultures after 72 hours of incubation. After infection-control education, a 28
      day interval assessment was used to examine contamination rates in newly provided
      ultrasound gel. The ability of ultrasound gel containing parabens to prevent
      bacterial growth was examined in cultures grown with and without ultrasound gel.
      RESULTS: Practitioners were not compliant with Health Canada recommendations, but
      the baseline ultrasound gel contamination rate within these departments was only
      2.5%. Education in infection control did not improve the contamination rate over
      28 days. Contamination was discovered in ultrasound gel supplied directly from
      the manufacturer. Ultrasound gel suppressed but did not prevent bacterial growth
      in a species- and time-specific manner. CONCLUSIONS: The source of contamination
      for in-use ultrasound gel may be of manufacturer or human origin. Because
      additives to the ultrasound gel are not bactericidal, sterile ultrasound gel
      should be used for invasive and high-risk cases, and improving infection-control
      policies is warranted.

PMID- 23974867
TI  - A case report of two male siblings with autism and duplication of Xq13-q21, a
      region including three genes predisposing for autism.
AB  - Autism spectrum disorder, severe behaviour problems and duplication of the Xq12
      to Xq13 region have recently been described in three male relatives. To describe
      the psychiatric comorbidity and dysmorphic features, including craniosynostosis,
      of two male siblings with autism and duplication of the Xq13 to Xq21 region, and
      attempt to narrow down the number of duplicated genes proposed to be leading to
      global developmental delay and autism. We performed DNA sequencing of certain
      exons of the TWIST1 gene, the FGFR2 gene and the FGFR3 gene. We also performed
      microarray analysis of the DNA. In addition to autism, the two male siblings
      exhibited severe learning disability, self-injurious behaviour, temper tantrums
      and hyperactivity, and had no communicative language. Chromosomal analyses were
      normal. Neither of the two siblings showed mutations of the sequenced exons known
      to produce craniosynostosis. The microarray analysis detected an extra copy of a
      region on the long arm of chromosome X, chromosome band Xq13.1-q21.1. Comparison
      of our two cases with previously described patients allowed us to identify three
      genes predisposing for autism in the duplicated chromosomal region. Sagittal
      craniosynostosis is also a new finding linked to the duplication. 

PMID- 23974868
TI  - The current state of genetic counseling before and after amniocentesis for fetal
      karyotyping in Japan: a survey of obstetric hospital clients of a prenatal
      testing laboratory.
AB  - Pregnant women undergoing prenatal genetic testing should receive genetic
      counseling so they can make informed decisions. We examined the current state of
      providing genetic counseling in Japan to pregnant women before they elected
      amniocentesis for prenatal diagnosis of chromosome abnormalities and after test
      results were completed, and explored the opportunity for expanding access to
      certified genetic counselors (CGC) at clinical practices offering amniocentesis.
      An anonymous survey was mailed to the 298 hospitals that referred amniotic fluid
      specimens to LabCorp Japan in 2009. Most genetic counseling was provided by the
      obstetrician alone; 73.8 % (76/103) of pre-amniocentesis, 82.5 % (85/103) if
      normal results, and 49.4 % (44/89) if abnormal results. Respondents spent limited
      time in genetic counseling; 57.3 % spent <10 min for pre-amniocentesis, 88.3 %
      spent <10 min for normal results, and 54.0 % spent <20 min for abnormal results.
      While 45.8 % indicated that CGC do not have an essential role in clinical
      practice, responses that supported employment of CGC were more likely to come
      from hospitals that submitted more than ten specimens annually (p < 0.0001),
      university hospitals (p < 0.0001), and MD geneticists (p = 0.020). Currently,
      there is limited genetic counseling available in Japan. This indicates there are
      opportunities for the employment of CGC to improve the quality of genetic
      counseling. 

PMID- 23974869
TI  - Glutathione peroxidase activity is neuroprotective in models of Huntington's
      disease.
AB  - Huntington's disease is a fatal neurodegenerative disorder caused by a CAG repeat
      expansion encoding a polyglutamine tract in the huntingtin (Htt) protein. Here we
      report a genome-wide overexpression suppressor screen in which we identified 317
      ORFs that ameliorate the toxicity of a mutant Htt fragment in yeast and that have
      roles in diverse cellular processes, including mitochondrial import and copper
      metabolism. Two of these suppressors encode glutathione peroxidases (GPxs), which
      are conserved antioxidant enzymes that catalyze the reduction of hydrogen
      peroxide and lipid hydroperoxides. Using genetic and pharmacological approaches
      in yeast, mammalian cells and Drosophila, we found that GPx activity robustly
      ameliorates Huntington's disease-relevant metrics and is more protective than
      other antioxidant approaches tested here. Notably, we found that GPx activity,
      unlike many antioxidant treatments, does not inhibit autophagy, which is an
      important mechanism for clearing mutant Htt. Because previous clinical trials
      have indicated that GPx mimetics are well tolerated in humans, this study may
      have important implications for treating Huntington's disease. 

PMID- 23974870
TI  - Defining the disease liability of variants in the cystic fibrosis transmembrane
      conductance regulator gene.
AB  - Allelic heterogeneity in disease-causing genes presents a substantial challenge
      to the translation of genomic variation into clinical practice. Few of the almost
      2,000 variants in the cystic fibrosis transmembrane conductance regulator gene
      CFTR have empirical evidence that they cause cystic fibrosis. To address this
      gap, we collected both genotype and phenotype data for 39,696 individuals with
      cystic fibrosis in registries and clinics in North America and Europe. In these
      individuals, 159 CFTR variants had an allele frequency of l0.01%. These variants
      were evaluated for both clinical severity and functional consequence, with 127
      (80%) meeting both clinical and functional criteria consistent with disease.
      Assessment of disease penetrance in 2,188 fathers of individuals with cystic
      fibrosis enabled assignment of 12 of the remaining 32 variants as neutral,
      whereas the other 20 variants remained of indeterminate effect. This study
      illustrates that sourcing data directly from well-phenotyped subjects can address
      the gap in our ability to interpret clinically relevant genomic variation. 

PMID- 23974871
TI  - Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and
      metabolic wasting.
AB  - The relative contribution of immunological dysregulation and impaired epithelial
      barrier function to allergic diseases is still a matter of debate. Here we
      describe a new syndrome featuring severe dermatitis, multiple allergies and
      metabolic wasting (SAM syndrome) caused by homozygous mutations in DSG1. DSG1
      encodes desmoglein 1, a major constituent of desmosomes, which connect the cell
      surface to the keratin cytoskeleton and have a crucial role in maintaining
      epidermal integrity and barrier function. Mutations causing SAM syndrome resulted
      in lack of membrane expression of DSG1, leading to loss of cell-cell adhesion. In
      addition, DSG1 deficiency was associated with increased expression of a number of
      genes encoding allergy-related cytokines. Our deciphering of the pathogenesis of
      SAM syndrome substantiates the notion that allergy may result from a primary
      structural epidermal defect. 

PMID- 23974874
TI  - Mucosal immunity and the onset of allergic disease.
AB  - Mucosal barriers encounter an environment that is rich in pathogens that possess
      mechanisms for invading mucosal tissues. These barriers also encounter innocuous
      antigens, such as foods, airborne antigens, and microbiota. The mucosa has
      developed a sophisticated immune system that can mount robust immune responses
      against pathogenic antigens, while maintaining mucosal tolerance against non
      pathogenic antigens. Accumulating evidence indicates that the mucosal epithelium,
      dendritic cells, and a subtype of T cells with regulatory properties play
      important roles in the development and maintenance of mucosal tolerance.
      Moreover, the micribiota also contribute to regulating the mucosal immune system.
      A failure to develop or the breakdown of mucosal tolerance can result in allergic
      diseases, such as food allergy and asthma. By taking advantage of the unique
      characteristics of the mucosal immune system, strategies that induce regulatory
      cells in vivo and, thereby, reconstitute mucosal tolerance may be used to develop
      novel therapies that are suitable for treating or preventing of allergic
      diseases. 

PMID- 23974875
TI  - Epicutaneous immunity and onset of allergic diseases - per-"eczema"tous
      sensitization drives the allergy march.
AB  - Results from recent epidemiological studies strongly suggest that ingestion of
      food promotes immune tolerance to food antigens, whereas exposure to food
      antigens through skin leads to allergic sensitization. A "dual-allergen-exposure
      hypothesis" has been proposed to explain those findings. However, several other
      recent studies have demonstrated that some allergic diseases can be successfully
      treated by recurrent epicutaneous exposure to allergens. At a glance, these two
      sets of findings seem to be contradictory, but we think they provide important
      clues for understanding the mechanisms behind the allergy march. Here, we propose
      that per-"eczema"tous sensitization drives the allergy march, and we introduce
      results from several published studies in support of this hypothesis. We hope
      that this review may help in establishment of new strategies for preventing the
      allergy march in the near future. 

PMID- 23974876
TI  - Gastrointestinal food allergy in infants.
AB  - Food allergies are classified into three types, "IgE-mediated," "combined IgE-
      and cell-mediated" and "cell-mediated/non-IgE-mediated," depending on the
      involvement of IgE in their pathogenesis. Patients who develop predominantly
      cutaneous and/or respiratory symptoms belong to the IgE-mediated food allergy
      type. On the other hand, patients with gastrointestinal food allergy (GI allergy)
      usually develop gastrointestinal symptoms several hours after ingestion of
      offending foods; they belong to the cell-mediated/non-IgE-mediated or combined
      IgE- and cell-mediated food allergy types. GI allergies are also classified into
      a number of different clinical entities: food protein-induced enterocolitis
      syndrome (FPIES), food protein-induced proctocolitis (FPIP), food protein-induced
      enteropathy (Enteropathy) and eosinophilic gastrointestinal disorders (EGID). In
      the case of IgE-mediated food allergy, the diagnostic approaches and pathogenic
      mechanisms are well characterized. In contrast, the diagnostic approaches and
      pathogenic mechanisms of GI allergy remain mostly unclear. In this review, we
      summarized each type of GI allergy in regard to its historical background and
      updated clinical features, offending foods, etiology, diagnosis, examinations,
      treatment and pathogenesis. There are still many problems, especially in regard
      to the diagnostic approaches for GI allergy, that are closely associated with the
      definition of each disease. In addition, there are a number of unresolved issues
      regarding the pathogenic mechanisms of GI allergy that need further study and
      elucidation. Therefore, we discussed some of the diagnostic and research issues
      for GI allergy that need further investigation. 

PMID- 23974877
TI  - The relationship between pollen count levels and prevalence of Japanese cedar
      pollinosis in Northeast Japan.
AB  - BACKGROUND: The prevalence of Japanese cedar (JC) pollinosis in Japanese children
      is increasing. However, few studies have reported the relationship between pollen
      count levels and the prevalence of pollinosis. To evaluate the relationship
      between JC pollen count levels and the prevalence of pollinosis in children, we
      investigated the sensitization and development of symptoms for JC pollen in two
      areas of Akita in northeast Japan with contrasting levels of exposure to JC
      pollen. METHODS: The study population consisted of 339 elementary school students
      (10-11 years of age) from the coastal and mountainous areas of Akita in 2005
      2006. A questionnaire about symptoms of allergic rhinitis was filled out by the
      students' parents. A blood sample was taken to determine specific IgE antibodies
      against five common aeroallergens. RESULTS: The mean pollen count in the
      mountainous areas was two times higher than that in the coastal areas in 1996
      2006. The prevalence rates of nasal allergy symptoms and sensitization for mites
      were almost the same in both areas. On the other hand, the rates of nasal allergy
      symptoms and sensitization for JC pollen were significantly higher in the
      mountainous areas than in the coastal areas. The rate of the development of
      symptoms among children sensitized for JC pollen was almost the same in both
      areas. CONCLUSIONS: These results suggest that pollen count levels may correlate
      with the rate of sensitization for JC pollinosis, but may not affect the rate of
      onset among sensitized children in northeast Japan.

PMID- 23974878
TI  - Secondary descemet membrane endothelial keratoplasty after failed primary
      descemet membrane endothelial keratoplasty: clinical results.
AB  - PURPOSE: To evaluate the clinical outcome of a secondary Descemet membrane
      endothelial keratoplasty (DMEK) to manage graft failure after primary DMEK.
      METHODS: Retrospective analysis of graft failure after primary DMEK treated with
      a second DMEK. The clinical outcome was evaluated by comparing the pre- to
      postoperative best-corrected visual acuity (BCVA) after first and second DMEK.
      RESULTS: In 122 DMEKs performed, 6 patients were included because of nonclearing
      edema or graft detachment. Ten of 122 grafts failed, 8 had a second DMEK, and 6
      had an adequate follow-up with visual potential to be included in the visual
      acuity analysis. All patients had Fuchs dystrophy as the underlying disease for
      the endothelial decompensation. Average time to the second surgery was 2.9 months
      (1-5 months). Mean follow-up after second DMEK was 3.3 months (1-6 months). BCVA
      was 0.63 +/- 0.22 logarithm of the minimum angle of resolution (logMAR)
      preoperatively and decreased to 1.50 +/- 0.28 logMAR after first surgery (mean
      follow-up, 2.9 months; P < 0.001). BCVA increased to 0.13 +/- 0.05 after
      successful second DMEK (mean follow-up, 3.3 months; P < 0.001). All second DMEKs
      were successful. CONCLUSIONS: To manage DMEK cases with graft failure, secondary
      DMEK may be a feasible procedure potentially resulting in full visual
      rehabilitation, as in primary DMEK. In the event of a DMEK graft failure, a
      secondary DMEK may be an effective back-up procedure because it may give a
      clinical outcome similar to that given after a primary DMEK.

PMID- 23974872
TI  - Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
AB  - Schizophrenia is an idiopathic mental disorder with a heritable component and a
      substantial public health impact. We conducted a multi-stage genome-wide
      association study (GWAS) for schizophrenia beginning with a Swedish national
      sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous
      schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication
      of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762
      controls and 581 parent-offspring trios). We identified 22 loci associated at
      genome-wide significance; 13 of these are new, and 1 was previously implicated in
      bipolar disorder. Examination of candidate genes at these loci suggests the
      involvement of neuronal calcium signaling. We estimate that 8,300 independent,
      mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to
      risk for schizophrenia and that these collectively account for at least 32% of
      the variance in liability. Common genetic variation has an important role in the
      etiology of schizophrenia, and larger studies will allow more detailed
      understanding of this disorder. 

PMID- 23974879
TI  - Amniotic Membrane Transplantation for the Treatment of Infectious Ulcerative
      Keratitis Before Elective Penetrating Keratoplasty.
AB  - PURPOSE: Emergency keratoplasties for inflamed eyes are considered to have a
      worse prognosis because of immunologic graft rejection. Amniotic membranes have
      antiinflammatory and antiangiogenic abilities. Therefore, amniotic membrane
      transplantation (AMT) was performed to stabilize the situation of eyes with
      severe infectious keratitis before elective penetrating keratoplasty (PK).
      METHODS: Retrospective, nonrandomized observational case series. Seven to 41 days
      (median, 20 days) after the onset of intensive antiinfectious medication, an AMT
      (6 multigrafts and 6 sandwich) was performed in 12 patients [8 men and 4 women;
      age 46-80 years (median, 66 years)] with herpetic (n = 5), bacterial keratitis (n
      = 3), or combinations (n = 4). Three to 12 months (median, 5 months) after
      cessation of the inflammatory status of the eye, a central elective PK (diameter,
      7-8 mm) became feasible in 10 eyes. Follow-up ranged from 4 to 38 months (median,
      20 months) after PK. RESULTS: The primary success rate of AMT was 11/12 (92%).
      Five recurrences (41%) were treated successfully 4 times by repeat AMT (sandwich)
      and 1 time by emergency PK. In 2 of the 12 eyes, an irreversible endothelial
      immunologic graft reaction appeared 18 and 21 months after PK. One eye suffered
      from reversible recurrence of herpetic keratitis on the corneal graft. At the end
      of the follow-up, 10 of 12 grafts (83%) were clear. CONCLUSIONS: A rapid decrease
      in the inflammatory reaction and a fast reepithelialization because of AMT after
      intensive antiinfectious medication in case of severe ulcerative keratitis may
      help to avoid an emergency keratoplasty and improves the prognosis of the
      elective keratoplasty.

PMID- 23974873
TI  - Neuroimaging biomarkers in mild traumatic brain injury (mTBI).
AB  - Reviewed herein are contemporary neuroimaging methods that detect abnormalities
      associated with mild traumatic brain injury (mTBI). Despite advances in
      demonstrating underlying neuropathology in a subset of individuals who sustain
      mTBI, considerable disagreement persists in neuropsychology about mTBI outcome
      and metrics for evaluation. This review outlines a thesis for the select use of
      sensitive neuroimaging methods as potential biomarkers of brain injury
      recognizing that the majority of individuals who sustain an mTBI recover without
      neuroimaging signs or neuropsychological sequelae detected with methods currently
      applied. Magnetic resonance imaging (MRI) provides several measures that could
      serve as mTBI biomarkers including the detection of hemosiderin and white matter
      abnormalities, assessment of white matter integrity derived from diffusion tensor
      imaging (DTI), and quantitative measures that directly assess neuroanatomy.
      Improved prediction of neuropsychological outcomes in mTBI may be achieved with
      the use of targeted neuroimaging markers. 

PMID- 23974880
TI  - Corneal Collagen Cross-Linking for the Treatment of Acanthamoeba Keratitis.

PMID- 23974881
TI  - Diurnal Pattern of Tear Osmolarity and Its Relationship to Corneal Thickness and
      Deswelling.
AB  - PURPOSE: To identify the diurnal variations of tear osmolarity (TO) and its
      relationship with central corneal thickness (CCT) and corneal deswelling over a
      14-hour period. METHODS: TO and CCT were measured using the TearLab Osmometer and
      Bioptigen spectral domain optical coherence tomography, respectively, on 38
      healthy neophytes (mean age, 21.5 +/- 2.2 years). TO and CCT were measured at
      bedtime (baseline), upon awakening, 20 minutes, 40 minutes, 1 hour, 2 hours, 4
      hours, and 8 hours after awakening. Deswelling rate was estimated and expressed
      as percent recovery per hour (PRPH). Mixed-effect linear regression models
      describe the relationships among TO, CCT, and PRPH. RESULTS: The tear film upon
      wakening (264 +/- 14 mOsm/L) was hypoosmotic compared with baseline (297 +/- 15
      mOsm/L, P < 0.001). TO (in mOsm/L) at 20 minutes, 40 minutes, 1 hour, 2 hours, 4
      hours, and 8 hours were 287 +/- 10, 292 +/- 16, 293 +/- 12, 292 +/- 10, 289 +/-
      10, and 286 +/- 10, respectively. CCT (mean +/- SD) at baseline was 552.2 +/-
      35.9 um and increased to 572.0 +/- 38.7 um after sleep. CCT returned to baseline
      thickness 4 hours after awakening (P < 0.000) and remained stable throughout the
      day. A small but statistically significant association was found between higher
      TO and lower CCT (P < 0.0001) and between lower baseline TO and higher PRPH
      (faster deswelling; P < 0.0001). CONCLUSIONS: The diurnal pattern of TO has been
      established. The association of TO with corneal thickness and deswelling suggests
      that the tear film tonicity may be partly responsible for corneal hydration
      control; however, the effect may not be of clinical significance in a normal
      study cohort.

PMID- 23974882
TI  - Increased Expression of Aquaporin-1 and Aquaporin-3 in Pterygium.
AB  - PURPOSE: Recent studies have shown that aquaporins (AQPs) play an important role
      in proliferating tumor microvessels and angiogenesis. In this study, the authors
      investigated the expression of aquaporin-1 (AQP1) and aquaporin-3 (AQP3) in
      pterygial and normal conjunctival tissues. METHODS: Fifteen patients with
      pterygium were enrolled in the study. Pterygium was excised, and a conjunctival
      rotational flap or autograft was inserted. Normal conjunctival tissue was
      obtained from the flap or graft. Western blot analysis was performed to assess
      the expression of AQP1 and AQP3 in pterygial and normal conjunctival tissues.
      Tissue localization of AQP1 and AQP3 was determined by immunohistochemical
      analysis. RESULTS: AQP1 and AQP3 are localized in the epithelial and
      subepithelial regions in pterygial and normal conjunctival tissues. Protein
      expression of both AQP1 and AQP3 was elevated in pterygia when compared with
      conjunctival tissues. The significant increase in protein expression of AQP1 was
      3-fold in pterygium over normal conjunctiva (P = 0.004) and 2-fold increase in
      AQP3 expression of pterygium was detected (P = 0.02) according to densitometric
      analysis. CONCLUSIONS: Elevated protein expression of AQP1 and AQP3 was observed
      in pterygial tissues when compared with normal conjunctiva. The data suggest that
      the increased expression of AQP1 and AQP3 in pterygial tissues may be involved in
      the pathogenesis of pterygia, and therefore, AQP1 and AQP3 are potential
      therapeutic targets for preventing or delaying the progression of the disease.

PMID- 23974883
TI  - Scleral Patch Graft Augmented Cyanoacrylate Tissue Adhesive for Treatment of
      Moderate-Sized Noninfectious Corneal Perforations (3.5-4.5 mm).
AB  - PURPOSES: To describe a new technique of scleral tissue augmented cyanoacrylate
      tissue adhesive (CTA) application and to evaluate its efficacy in noninfectious
      corneal perforations that measure between 3.5 and 4.5 mm. METHODS: Retrospective
      noncomparative case series included 16 consecutive patients diagnosed with
      moderate-sized corneal perforations measuring 3.5 to 4.5 mm who were treated with
      scleral patch graft augmented glue application. A partial-thickness scleral patch
      equal to the size of corneal perforation was placed in the corneal perforation
      site. After the area was sufficiently dried, CTA was applied on the interface of
      the host cornea and scleral patch. The ability of the scleral patch graft with
      CTA to seal the perforation and allow complete wound healing was considered a
      successful outcome. RESULTS: The corneal perforation healed in 14 eyes (87.5%),
      with a mean of 5.65 weeks (range, 5-9 weeks). One eye (6.25%) developed
      microperforation that required additional CTA to seal the wound. Three eyes
      (18.75%) required reapplication of the scleral patch graft and CTA. The 2 eyes
      (12.50%) that failed scleral patch with CTA were successfully treated with
      tectonic penetrating keratoplasties. In all 5 eyes (100%), the corneal
      perforations as a result of Mooren ulcer healed in a mean 5.80 weeks (range, 5-7
      weeks). One patient developed retinal detachment with proliferative
      vitreoretinopathy and cataract after trauma. CONCLUSIONS: Scleral patch graft
      augmented CTA technique is a successful alternative treatment method to emergent
      penetrating keratoplasty for corneal perforations that measure 3.5 to 4.5 mm.

PMID- 23974884
TI  - Assessing the Reproducibility of Quantitative In Vivo Confocal Microscopy of
      Corneal Nerves in Different Corneal Locations.
AB  - PURPOSE: To evaluate the reproducibility of in vivo confocal microscopy for
      quantitative corneal nerve analysis in different corneal locations. METHODS:
      Corneal confocal microscopy was performed on 10 healthy participants, and the
      corneal nerve fiber length, corneal nerve fiber density, corneal nerve branch
      density, and tortuosity coefficient were measured at 5 predetermined locations
      for only the right eye. Bland-Altman plots, intraclass correlation coefficient
      (ICC), and coefficient of variation of all 4 corneal nerve measurements were
      compared between 2 visits and between readers to assess reproducibility. Two
      technicians performed a masked analysis of images from both visits. RESULTS: Ten
      participants with a mean age of 31.3 +/- 2.8 years were imaged at 2 different
      time points separated by a mean of 4.3 +/- 4.3 weeks. The interobserver
      agreements were better than the intervisit agreements for all the 4 corneal nerve
      measurements as evaluated using Bland-Altman plots. The intervisit ICC ranged
      from 0.13 to 0.45, and the interobserver ICC ranged from 0.55 to 0.94. The
      differences between observers and the differences between sessions were not
      statistically different among all the 5 locations (P > 0.1) for each corneal
      nerve measurement. CONCLUSIONS: Single confocal images have poor reliability for
      any of the 4 corneal nerve measurements, and there is no single location on the
      cornea that has improved reproducibility. Averaging 5 images, from different
      locations, improves the reproducibility and is essential for obtaining clinically
      meaningful data.

PMID- 23974885
TI  - Randomized Controlled Study of Ocular Lubrication Versus Bandage Contact Lens in
      the Primary Treatment of Recurrent Corneal Erosion Syndrome.
AB  - PURPOSE: To investigate the efficacy of bandage contact lenses (BCLs) in
      comparison with that of ocular lubricants (OLs) in the initial management of
      recurrent corneal erosion syndrome. METHODS: A randomized controlled trial of 29
      patients with recurrent corneal erosion syndrome presenting to the ophthalmology
      departments of the Oxford Eye Hospital and the Royal Berkshire Hospital, United
      Kingdom. The patients were randomized to wear either BCLs (for a 3-month
      duration, replaced every 30 days) or use OLs (4 times a day, with Lacri-Lube
      ointment at night for 3 months). The patients were assessed monthly for 4 months,
      and their symptoms were graded by visual analog scores. The main outcome measure
      was the complete resolution of symptoms with no noticeable corneal surface
      abnormality. Patients with a complete resolution were followed up for another 3
      months to check for recurrence. RESULTS: Fourteen patients were randomized to the
      BCL arm, and 15 were randomized to the OL arm. After 3 months, a complete
      resolution was achieved in 71% of the patients (10/14) with BCLs compared with
      that achieved in 73% of the patients (11/15) on OLs (P > 0.05). Partial
      resolution was noted in 7% of the patients with BCLs versus 13% of the patients
      on OLs. Twenty-one percent of the patients in the BCL group and 13% of the
      patients in the OL group failed to respond to the treatment. Patients on BCLs had
      earlier resolution of symptoms, with a mean time of 5 weeks compared with 9 weeks
      for OLs (P = 0.02). None of the patients with BCLs developed adverse side
      effects. CONCLUSIONS: BCLs do not increase the likelihood of complete resolution
      when compared with OLs in the initial management of RCES. However, BCL treatment
      seems safe, and some patients experience earlier relief from symptoms.

PMID- 23974886
TI  - Scleral and intraocular amoebic dissemination in Acanthamoeba keratitis.
AB  - PURPOSE: To review an Acanthamoeba keratitis case series for the documented
      extracorneal spread of the amoeba. METHODS: A retrospective review of an
      observational case series from a single institution. RESULTS: Three patients with
      4 instances of microbiologically confirmed extracorneal amoebic spread were
      identified. Patient 1 had nodular scleritis after undergoing penetrating
      keratoplasty and was treated successfully with double freeze-thaw cryotherapy;
      patient 2 had intraocular dissemination of the amoeba detected in a retrocorneal
      membrane; and patient 3 had, after undergoing tectonic keratoplasty, intraocular
      dissemination of the amoeba that was treated successfully with intraocular and
      systemic voriconazole and, afterwards, a nodular scleritis treated with double
      freeze-thaw cryotherapy and a large-diameter corneal graft to treat corneal
      recurrence. CONCLUSIONS: Acanthamoeba can migrate to the sclera or to the
      intraocular tissues in some instances, such as in long-standing disease or in
      penetrating keratoplasty. A prompt biopsy for microbiological analysis and early
      treatment are required, if this is suspected. Voriconazole can be effective for
      intraocular invasion when used orally and intraocularly. Scleral involvement
      might require a surgical approach with double freeze-thaw cryotherapy to treat
      the localized disease.

PMID- 23974887
TI  - Delayed Epithelial Closure After PRK Associated With Topical Besifloxacin Use.
AB  - PURPOSE: To report the observation of prolonged reepithelialization after
      photorefractive keratectomy (PRK) associated with the use of besifloxacin 0.6%
      (Besivance; Bausch & Lomb, Rochester, NY) underneath bandage contact lenses
      (BCLs) placed during surgery. METHODS: An office-based private practice and
      retrospective chart review. The healing parameters examined included epithelial
      healing time, haze formation, discomfort, and visual recovery of 4 patients (7
      eyes) treated with besifloxacin 0.6% under BCLs placed after the PRK was
      performed. RESULTS: All the eyes had delayed epithelial closure (mean, 8.8 days;
      range 5-13 days). All the patients experienced a delayed visual recovery and
      significant pain after the surgery, and 2 of 4 patients experienced recurrent
      corneal erosions for weeks to months after they underwent the PRK. All but 1 eye
      developed corneal haze persisting for 1 year or more after the surgery. Only 1
      eye among the 7 eyes treated with besifloxacin 0.6% under the BCL had 20/20 or
      better uncorrected visual acuity 3 months postoperatively. CONCLUSIONS: All the
      patients treated with besifloxacin 0.6% on the stromal bed exhibited significant
      problems with corneal epithelial healing and delayed visual recovery. We caution
      the use of besifloxacin 0.6% underneath a BCL during a PRK or other ocular
      surface surgeries requiring corneal epithelial debridement.

PMID- 23974888
TI  - Algorithm for correcting the keratometric error in the estimation of the corneal
      power in eyes with previous myopic laser refractive surgery.
AB  - PURPOSE: To calculate theoretically the errors in the estimation of corneal power
      when using the keratometric index (nk) in eyes that underwent laser refractive
      surgery for the correction of myopia and to define and validate clinically an
      algorithm for minimizing such errors. METHODS: Differences between corneal power
      estimation by using the classical nk and by using the Gaussian equation in eyes
      that underwent laser myopic refractive surgery were simulated and evaluated
      theoretically. Additionally, an adjusted keratometric index (nkadj) model
      dependent on r1c was developed for minimizing these differences. The model was
      validated clinically by retrospectively using the data from 32 myopic eyes
      [range, -1.00 to -6.00 diopters (D)] that had undergone laser in situ
      keratomileusis using a solid-state laser platform. The agreement between Gaussian
      (Pc) and adjusted keratometric (Pkadj) corneal powers in such eyes was evaluated.
      RESULTS: It was found that overestimations of corneal power up to 3.5 D were
      possible for nk = 1.3375 according to our simulations. The nk value to avoid the
      keratometric error ranged between 1.2984 and 1.3297. The following nkadj models
      were obtained: nkadj = -0.0064286r1c + 1.37688 (Gullstrand eye model) and nkadj =
      -0.0063804r1c + 1.37806 (Le Grand). The mean difference between Pkadj and Pc was
      0.00 D, with limits of agreement of -0.45 and +0.46 D. This difference correlated
      significantly with the posterior corneal radius (r = -0.94, P < 0.01).
      CONCLUSIONS: The use of a single nk for estimating the corneal power in eyes that
      underwent a laser myopic refractive surgery can lead to significant errors. These
      errors can be minimized by using a variable nk dependent on r1c.

PMID- 23974889
TI  - A Technique to Rescue Keratoprosthesis Melts.
AB  - PURPOSE: To describe a technique to completely replace the donor corneal carrier
      of an existing type 1 Boston keratoprosthesis (KPro) that preserves the hardware
      intact. METHODS: Two eyes with sterile corneal melts around the KPro stem
      underwent a complete exchange of the donor corneal carrier. Donor corneas were
      prepared in the usual fashion for KPro and were then left uncovered to dehydrate.
      Meanwhile, the melted corneas were excised in a manner similar to that for failed
      penetrating grafts and uncollared from the KPro. The new donors were then
      sufficiently thinned to slide between the back and front plates; however, to
      clear the 5.0-mm KPro front plate flange, the central 3.0-mm opening in the
      replacement donor corneas was first enlarged by means of 2 paired sub-1.0-mm
      radial relaxing incisions placed 180 degrees apart. Once positioned, the new
      donor carriers were rehydrated to seal the space between the back and front
      plates. RESULTS: The full-thickness corneal carrier was successfully replaced in
      both cases. In 1 case, scarring of the back plate holes caused the plate to
      behave like an intact Descemet membrane during deep anterior lamellar
      keratoplasty. CONCLUSIONS: When an otherwise functional KPro is jeopardized
      because of disorders of the donor corneal carrier, it can be advantageous to
      selectively replace the carrier and thus salvage the original KPro. We describe
      such a rescue technique, which permits the exchange of the corneal carrier
      without disassembling the KPro.

PMID- 23974891
TI  - Postoperative trendelenburg position for graft adherence after descemet stripping
      automated endothelial keratoplasty.
AB  - PURPOSE: To present a case of repeated graft dislocation after Descemet stripping
      automated endothelial keratoplasty (DSAEK) in a post-trabeculectomy eye and to
      suggest a simple postoperative maneuver to minimize this occurrence. METHODS: A
      61-year-old woman presented to our cornea clinic with pseudophakic bullous
      keratopathy in her left eye 13 years after a trabeculectomy had been performed.
      After the DSAEK was performed, repeated graft dislocations were observed. When
      air was seen in the filtering bleb in the immediate postoperative period, it was
      assumed that it had escaped from the air bubble remaining in the anterior chamber
      at the end of the surgery. The patient was thus placed in the Trendelenburg
      position immediately after performing a rebubbling procedure to retain the air
      bubble in the anterior chamber and away from the filtering bleb. RESULTS: The
      corneal graft remained centered and clear at postoperative day 1 and remained so
      at the last follow-up visit 8 months after the surgery had taken place. The
      patient's intraocular pressure was well controlled with a functional filtering
      bleb. CONCLUSIONS: Postoperative Trendelenburg positioning is an easily applied
      maneuver that may promote graft adherence after performing a DSAEK in eyes that
      have undergone glaucoma surgery.

PMID- 23974890
TI  - Epidemiology of Ocular Surface Squamous Neoplasia in a Veterans Affairs
      Population.
AB  - PURPOSE: To evaluate the epidemiology of ocular surface squamous neoplasia (OSSN)
      and its associated risk factors in a South Florida Veterans Affairs Hospital
      population. METHODS: Retrospective case-control study. Twenty-eight confirmed
      cases of OSSN from 24,179 veterans who received care at the Miami Veterans
      Affairs Healthcare System and affiliated satellite eye clinics between March 1,
      2007, and March 1, 2012. Data extracted from the veterans administration database
      that comprised demographic information and medical diagnosis information [based
      on International Classification of Disease (ICD-9) codes]. The main outcome
      measures were the period prevalence of OSSN and identification of factors
      associated with the presence of disease. RESULTS: The period prevalence of OSSN
      in our population was 0.1%. The risk factors studied included UV-related
      dermatologic diseases (melanoma, squamous and basal cell cancer, and actinic
      keratosis), UV-related ocular conditions (pterygium), HIV seropositivity, human
      papilloma virus-related diseases, and tobacco use. The presence of skin
      malignancy (squamous cell carcinoma and/or basal cell carcinoma) and pterygium
      was found to be significantly associated with the presence of OSSN [odds ratio,
      4.40; 95% confidence interval, 2.03-9.55; P < 0.0005 and odds ratio, 16.2; 95%
      confidence interval, 7.11-36.9; P < 0.0005, respectively]. CONCLUSIONS: The
      presence of neoplasias and ocular conditions related to sun exposure was the most
      important risk factor for the occurrence of OSSN in a South Florida Veterans
      Affairs Healthcare System population consistent with previous epidemiological
      reports worldwide.

PMID- 23974892
TI  - Biological Stability of Plasma Rich in Growth Factors Eye Drops After Storage of
      3 Months.
AB  - PURPOSE: We evaluated whether plasma rich in growth factors eye drops maintain
      their composition and biological activity after storage for 3 months at -20
      degrees C and after storage at 4 degrees C or room temperature (RT) for 24 hours,
      compared with samples obtained at time 0 (fresh samples). METHODS: Blood from 10
      healthy donors was collected, centrifuged, and plasma rich in growth factors was
      prepared by avoiding the collection of the buffy coat. Eye drops were kept fresh
      or were stored at -20 degrees C for 15, 30, and 90 days. For each time, 2
      aliquots were kept at RT or at 4 degrees C for 24 hours. Osmolarity, vitamin A,
      fibronectin, platelet-derived growth factor-AB, vascular endothelial growth
      factor, epithelial growth factor, and transforming growth factor-beta1 were
      quantified. The proliferative and migratory potential of the eye drops was
      assayed on primary human keratocytes. RESULTS: Platelet-derived growth factor-AB,
      vascular endothelial growth factor, epithelial growth factor, and vitamin A
      levels remained constant for each time and for each storage condition, whereas
      fibronectin, transforming growth factor-beta1, and osmolarity values were
      slightly modified after freezing. Cell proliferation and migration were
      significantly enhanced with the biological eye drops independently of the time
      and the storage condition. No microbial contamination was observed in any plasma
      rich in growth factors eye drops. CONCLUSIONS: Plasma rich in growth factors eye
      drops can be stored for up to 3 months without any reduction of the main proteins
      involved in ocular surface healing. Their use during 24 hours either at 4 degrees
      C or at RT did not alter the composition and the in vitro biological activity of
      the eye drops.

PMID- 23974893
TI  - Comparative Analysis of Refractive and Topographic Changes in Early and Advanced
      Keratoconic Eyes Undergoing Corneal Collagen Crosslinking.
AB  - PURPOSE: To compare the refractive and topographic changes at 1 year in eyes with
      early and advanced keratoconus undergoing corneal collagen crosslinking (CXL). A
      prospective, nonrandomized comparative clinical intervention study. METHODS:
      Thirty eyes of patients with keratoconus underwent CXL. They were divided into 2
      groups based on their mean central keratometry: group A [mean central K <= 53
      diopters (D)] and group B (mean central K > 53 D). Uncorrected visual acuity
      (UCVA), best-corrected visual acuity (BCVA), refraction, topography, pachymetry,
      and endothelial cell counts were evaluated at baseline and at 1, 3, 6, and 12
      months of follow-up. RESULTS: The mean baseline logarithm of the minimum angle of
      resolution (logMAR) UCVA and logMAR BCVA in group A was 1.007 +/- 0.30 and 0.566
      +/- 0.21, respectively. The values improved to 0.727 +/- 0.29 (P = 0.001) and
      0.306 +/- 0.15 (P = 0.001) at 1-year post CXL. The mean baseline logMAR UCVA and
      logMAR BCVA in group B were 1.040 +/- 0.24 and 0.641 +/- 0.25, respectively. It
      changed to 0.953 +/- 0.26 (P = 0.054) and 0.633 +/- 0.27 (P = 0.891) at 1 year.
      The improvement in the UCVA and BCVA was statistically significant in group A as
      compared with that in group B. The mean baseline flattest, steepest, central, and
      apical keratometry in group A were 48.7 +/- 2.5 D, 54.9 +/- 3.3 D, 49.5 +/- 1.4
      D, and 57.3 +/- 2.3 D, respectively. At 12 months, the values changed to 47.8 +/-
      2.4 D, 54.1 +/- 3.0 D, 48.8 +/- 1.8 D, and 56.2 +/- 2.7 D, the change being
      statistically significant for mean flat and apical K only (P < 0.05). All the 4
      indices did not show any statistically significant difference at 12 months in
      group B (P > 0.05). CONCLUSIONS: Corneal CXL is more effective in improving the
      refractive and topographical parameters at 1 year when it is performed early in
      the course of the disease.

PMID- 23974894
TI  - Midinfrared Laser Pancorneal Coagulation as a Method of Treatment for Painful
      Bullous Keratopathy.
AB  - PURPOSE: To evaluate the efficacy of midinfrared laser pancorneal coagulation
      (PCC) for the management of secondary painful bullous keratopathy (PBK) with poor
      visual potential. METHODS: A single-center, nonrandomized, retrospective
      observational study was performed on 137 eyes (137 patients) with PBK that
      underwent midinfrared laser PCC and were followed up in our clinic during 2000 to
      2010. Preoperatively and at follow-up visits, all the eyes underwent a standard
      ophthalmologic examination; concurrently, 36 of these underwent corneal optical
      coherence tomography (OCT) and Scheimpflug camera examination (SCE). The main
      criteria for the efficacy of the treatment included a profile of the patients'
      corneal syndrome-related complaints (pain, dryness, etc), presence of bullae and
      deepithelization, and changes in the corneal thickness (CT) and transparency,
      based on OCT and SCE data, respectively, whereas additional ones included visual
      acuity changes. RESULTS: During the 24-month follow-up period, 69.3% of the
      patients had no complaints (complete epithelization), whereas 10.9% and 3.6%
      complained of having dryness and residual pain, respectively; the rest exhibited
      a recurrent corneal syndrome with isolated blister and/or corneal erosion areas,
      which was successfully managed with an additional focal-pattern laser coagulation
      session. In the OCT and SCE subgroup, on the day-3, day-7, and month-24 visits,
      the mean CT statistically significantly decreased from baseline (1027.1 +/-
      239.5) to 737.6 +/- 157.4 MUm, 592.3 +/- 96.4 MUm, and was 617 +/- 95.9 MUm,
      respectively, whereas the mean optical density decreased from the baseline (72.5
      +/- 9.5) to 62.3 +/- 7.8, 58.5 +/- 8.7, and was 56.33 +/- 8.1 Scheimpflug
      densitometry units, respectively. CONCLUSIONS: PCC is a simple procedure that
      provides prompt relief from pain for eyes that have PBK with poor visual
      potential due to the reduction in CT and significant resolution of bullae and
      edema.

PMID- 23974895
TI  - Childhood Mucous Membrane Pemphigoid: A Case With Exclusively Ocular Involvement.
AB  - PURPOSE: To report a case of mucous membrane pemphigoid (MMP) occurring in
      childhood with exclusively ocular involvement. METHODS: Case report. RESULTS: A
      12-year-old girl presented with mild bilateral conjunctival cicatrization,
      symblepharon, and peripheral inflammatory keratitis. No other mucosal or
      cutaneous involvement was present. The findings of an initial conjunctival biopsy
      with immunofluorescence study were negative for MMP. After a few recurrences of
      mild corneal and conjunctival inflammation, a second conjunctival biopsy was
      performed at a different site in the same eye, 30 months later. Only then was the
      diagnosis of MMP confirmed using positive direct immunofluorescence. The results
      of a systemic investigation for autoimmune vasculitis were negative. Therapy with
      dapsone was introduced, and a good response was obtained. CONCLUSIONS: MMP is an
      extremely rare condition in children. This case is the second one reported with
      exclusively ocular involvement. Despite its rarity in the pediatric age group,
      MMP should be considered in the differential diagnosis of chronic conjunctival
      inflammation and fibrosis. Furthermore, a single negative biopsy should not
      exclude this diagnosis in a suspected clinical case, even in children. When a
      high degree of suspicion is present, a repeat biopsy may prove useful.

PMID- 23974896
TI  - Serial Analysis of Anterior Chamber Depth and Angle Status Using Anterior Segment
      Optical Coherence Tomography After Boston Keratoprosthesis.
AB  - PURPOSE: To analyze iris behavior and angle status using serial anterior segment
      optical coherence tomography (AS-OCT) after Boston keratoprosthesis (KPro).
      METHODS: A prospective cases series consisted of 11 eyes with implanted type 1
      KPro at a tertiary care institution. The patients underwent preoperative and
      serial postoperative AS-OCT imaging. The main outcome measures included anterior
      chamber angle (ACA) at representative meridians (0 degrees, 45 degrees, 90
      degrees, 135 degrees, 180 degrees, 225 degrees, 270 degrees, and 315 degrees),
      grading of total ACA as open (>10 degrees), shallow (>=1 degrees and <=10
      degrees) or closed (<1 degrees), preoperative anterior chamber depth (ACD),
      postoperative anatomical and functional ACD, and the presence of iris-back plate
      touch and peripheral anterior synechiae. RESULTS: The mean follow-up with serial
      AS-OCT was 13.1 months. Preoperatively, 54.5%, 27.3%, and 18.2% of the eyes had
      open, shallow, and closed angles, respectively. The mean change in the effective
      ACD decreased postoperatively by 1.61 mm. At 0 degree and 180 degree meridians,
      the ACA decreased by a mean change of 6.95 degrees and 8.40 degrees, with a mean
      change of 8.12 degrees for all meridians. Eight (72.7%) eyes had synechiae with
      7.3 and 6.7 clock hours of peripheral anterior synechiae and iris-back plate
      touch. At the last follow-up, 7 (63.6%) eyes had considerable progression of
      angle closure (change in grading of total angle), and 18.2%, 36.4%, and 45.5% had
      open, shallow, and closed angles, respectively. CONCLUSIONS: KPro implantation
      induced progressive angle closure, shallowing of the anterior chamber, and
      synechiae formation that is not visible on clinical examination. Serial AS-OCT
      plays an important role in the detection and monitoring of progressive angle
      closure, and clinical correlation is needed to assess the association with
      glaucoma development or progression.

PMID- 23974897
TI  - Histologic Findings of Corneal Buttons in Decompensated Corneas With Toxic
      Anterior Segment Syndrome After Cataract Surgery.
AB  - PURPOSE: To report the histologic findings of penetrating keratoplasty buttons in
      decompensated corneas with toxic anterior segment syndrome (TASS) after a
      cataract surgery is performed. METHODS: We evaluated the histologic findings of
      16 corneal buttons of 16 patients who exhibited decompensation findings because
      of TASS by means of light microscopy. The patients were classified into 3 groups:
      The first group consisted of 5 corneal buttons with mild symptoms in which the
      central corneal thicknesses (CCTs) were <=650 MUm, and the visual acuities (VAs)
      were >=0.1. The second group consisted of 7 corneal buttons that exhibited
      moderate symptoms in which the CCTs were between 650 and 750 MUm and the VAs were
      between 0.1 and 0.03. The third group consisted of 4 corneal buttons that had
      severe symptoms in which the CCTs were >=750 MUm and the VAs were <=0.03.
      RESULTS: Light microscopy showed endothelial cell loss, vacuolated and thinned
      epithelial cell layers, disturbed collagen bonds, and Descemet membrane
      invaginations in patients in group I. Group II corneal buttons exhibited
      inflammatory cells (lymphocytes) and extended intercellular space between the
      epithelial cells, wrinkled Bowman membrane separated from the stroma in some
      local areas, stromal edema, and early vascularization. In group III, endothelial
      and epithelial cell layer loss, wrinkled Descemet and Bowman membranes,
      inflammatory cells, and structurally disturbed collagen bonds located beneath the
      Bowman membrane, and a greater amount of vascularization in the area of
      inflammation were observed. CONCLUSIONS: The results of the histologic evaluation
      of the decompensated corneas caused by the TASS are compatible with the clinical
      severity of the disease. In mild cases, the histologic findings were
      insignificant; however, when the clinical situation deteriorated, histologic
      findings became increasingly worse.

PMID- 23974898
TI  - Tissue Characteristics and Reported Adverse Events After Corneal Transplantation.
AB  - PURPOSE: To determine whether donor or tissue characteristics of corneas for
      transplantation are predictive of reported adverse events occurring in the early
      postoperative period. METHODS: We compared preoperative donor and tissue
      characteristics of corneal tissues with or without reported adverse events from
      2007 to 2011. Adverse event categories included primary graft failure, infection,
      surgical causes, recipient-related etiologies, and other causes. We included
      corneas transplanted via penetrating keratoplasty (PK) and endothelial
      keratoplasty (EK). RESULTS: Of 20,431 tissues included, there were 251 (1.2%)
      reported adverse events. Among all transplanted tissues, 67% were used for PK,
      and 33% were used for EK. The adverse event occurrence rate was 0.78% in PK
      versus 2.12% in EK (P < 0.0001). The donor characteristics associated with
      adverse events were male gender (P = 0.01) and cancer history (P = 0.03), which
      were associated with primary graft failure. In PK, the most frequently reported
      causes within 106 adverse events were recipient-related causes (n = 41, 0.30% of
      total PK tissues) and infection (n = 31, 0.23%). In EK, the most frequently
      reported causes within 145 adverse events were surgical complications (n = 72,
      1.05% of total EK tissues) and primary graft failure (n = 41, 0.60%).
      CONCLUSIONS: The rate of reported adverse events was low. Adverse events more
      commonly occurred after EK. Increased rate of primary graft failure was
      associated with male donors and donors with a cancer history. Postcut tissue
      thickness, only in the year 2007, was the sole tissue characteristic associated
      with adverse events.

PMID- 23974899
TI  - In Vitro Antimicrobial Long-Term Evaluation of Corneal Preservation Media Against
      Microorganisms Using A Closed-Chamber Study Model.
AB  - PURPOSE: To evaluate the existence of in vitro long-term antimicrobial activity
      of Optisol-GS against microorganisms related to corneal infection using a closed
      chamber study model. METHODS: Optisol-GS was contaminated with microorganisms
      related to corneal infections, and different times after contamination was
      analyzed using a closed-chamber study model. Microbial growths were analyzed by
      macroscopic observation. RESULTS: For Staphylococcus aureus and Pseudomonas
      aeruginosa, bacterial growth was observed in samples taken 1 hour through 7 days
      and 14 days after contamination occurred. For Staphylococcus epidermidis,
      Streptococcus agalactiae, and Candida albicans, microbial growth was observed in
      all samples studied. For Streptococcus pneumoniae, bacterial growth was observed
      in samples taken 1 hour through 72 hours after contamination. For Streptococcus
      pyogenes, bacterial growth was observed in samples taken 1 hour through 7 days
      after contamination. For Escherichia coli, bacterial growth was observed in
      samples taken 1 hour through 48 hours after contamination occurred. CONCLUSIONS:
      We conclude that no in vitro antimicrobial effect for any microorganism analyzed
      was observed in contaminated Optisol-GS after 72 hours; however, effective
      antimicrobial activity was observed for S. aureus, Str. pneumoniae, Str.
      pyogenes, P. aeruginosa, and E. coli after 7 to 10 days.

PMID- 23974901
TI  - Using data from seed-dispersal modelling to manage invasive tree species: the
      example of Fraxinus pennsylvanica Marshall in Europe.
AB  - Management strategies to control invasive species need information about
      dispersal distances to predict establishment potential. Fraxinus pennsylvanica is
      a North American anemochorous tree species that is invasive in many Central
      European floodplain forests. To predict seed-dispersal potential, the stochastic
      model WaldStat was used, which enables different options for directionality
      (isotropic and anisotropic) to be simulated. In this article, we (1) show
      empirical results of fructification and seed dispersal for this tree species. The
      model predicts approximately 250,000 seeds for one F. pennsylvanica tree. These
      results were used to (2) calculate species-specific dispersal distances and
      effects of wind direction. To consider the influence of wind on dispersal
      potential of the tree species, long-distance dispersal (LDD [95th percentile
      dispersal distance]) was calculated. Mean dispersal distances varied between 47
      and 66 m. LDD values modelled along the main wind direction ranged from 60 to 150
      m. Seed production, dispersal distance, and direction data were (3) incorporated
      into theoretical management scenarios for forest ecosystems. Finally (4), we
      discuss management options and the practical relevance of model scenarios in
      relation to the accuracy of spatial dispersal predictions. Further analyses
      should be focused on possible, well-adapted management concepts at stand level
      that could restrict the potential spread of invasive species. 

PMID- 23974902
TI  - Forest management devolution: gap between technicians' design and villagers'
      practices in Madagascar.
AB  - In the 1980s, tropical forest-management principles underwent a shift toward
      approaches giving greater responsibilities to rural people. One argument for such
      a shift were the long-term relations established between rural people and their
      natural resources. In Madagascar, a new law was drawn up in 1996 (Gelose law),
      which sought to integrate rural people into forest management. A gap was observed
      between the changes foreseen by the projects implementing the Gelose law and the
      actual changes. In this article, we use the concept of the social-ecological
      system (SES) to analyze that gap. The differences existing between the planned
      changes set by the Gelose contract in the village of Ambatoloaka (northwest of
      Madagascar) and the practices observed in 2010 were conceptualized as a gap
      between two SESs. The first SES is the targeted one (i.e., a virtual one); it
      corresponds to the designed Gelose contract. The second SES is the observed one.
      It is characterized by the heterogeneity of forest users and uses, which have
      several impacts on forest management, and by very dynamic social and ecological
      systems. The observed SES has been reshaped contingent on the constraints and
      opportunities offered by the Gelose contract as well as on other ecological and
      social components. The consequences and opportunities that such an SES reshaping
      would offer to improve the implementation of the Gelose law are discussed. The
      main reasons explaining the gap between the two SESs are as follows: (1) the
      clash between static and homogeneous perceptions in the targeted SES and the
      dynamics and heterogeneity that characterize the observed SES; and (2) the focus
      on one specific use of forest ecosystems (i.e., charcoal-making) in the targeted
      SES. Forest management in the observed SES depends on several uses of forest
      ecosystems. 

PMID- 23974903
TI  - Who visits a national park and what do they get out of it?: a joint visitor
      cluster analysis and travel cost model for Yellowstone National Park.
AB  - Yellowstone National Park visitor data were obtained from a survey collected for
      the National Park Service by the Park Studies Unit at the University of Idaho.
      Travel cost models have been conducted for national parks in the United States;
      however, this study builds on these studies and investigates how benefits vary by
      types of visitors who participate in different activities while at the park.
      Visitor clusters were developed based on activities in which a visitor
      participated while at the park. The clusters were analyzed and then incorporated
      into a travel cost model to determine the economic value (consumer surplus) that
      the different visitor groups received from visiting the park. The model was
      estimated using a zero-truncated negative binomial regression corrected for
      endogenous stratification. The travel cost price variable was estimated using
      both 1/3 and 1/4 the wage rate to test for sensitivity to opportunity cost
      specification. The average benefit across all visitor cluster groups was
      estimated at between $235 and $276 per person per trip. However, per trip
      benefits varied substantially across clusters; from $90 to $103 for the "value
      picnickers," to $185-$263 for the "backcountry enthusiasts," $189-$278 for the
      "do it all adventurists," $204-$303 for the "windshield tourists," and $323-$714
      for the "creature comfort" cluster group. 

PMID- 23974904
TI  - Environmental effectiveness of swine sewage management: a multicriteria AHP-based
      model for a reliable quick assessment.
AB  - Environmental issues related to swine production are still a major concern for
      the general public and represent a key challenge for the swine industry. The
      environmental impact of higher livestock concentration is particularly
      significant where it coincides with weaker policy standards and poor manure
      management. Effective tools for environmental monitoring of the swine sewage
      management process become essential for verifying the environmental compatibility
      of farming facilities and for defining suitable policies aimed at increasing
      swine production sustainability. This research aims at the development and
      application of a model for a quick assessment of the environmental effectiveness
      of the pig farming sewage management process. In order to define the model,
      multicriteria techniques, and in particular, Saaty's analytic hierarchy process,
      were used to develop an iterative process in which the various key factors
      influencing the process under investigation were analyzed. The model, named EASE
      (Environmental Assessment of Sewages management Effectiveness), was optimized and
      applied to the Lake Trasimeno basin (Umbria, Italy), an area of high natural,
      environmental and aesthetic value. In this context, inadequate disposal of pig
      sewage represents a potential source of very considerable pollution. The results
      have demonstrated how the multicriteria model can represent a very effective and
      adaptable tool also in those decision-making processes aimed at the sustainable
      management of livestock production. 

PMID- 23974905
TI  - Long-term renal denervation normalizes disrupted blood pressure circadian rhythm
      and ameliorates cardiovascular injury in a rat model of metabolic syndrome.
AB  - BACKGROUND: Although renal denervation significantly reduces blood pressure in
      patients with resistant hypertension, the role of the renal nerve in hypertension
      with metabolic syndrome is unknown. We investigated the impact of long-term renal
      denervation on SHR/NDmcr-cp(+/+) (SHRcp) rats, a useful rat model of metabolic
      syndrome, to determine the role of the renal nerve in hypertension with metabolic
      syndrome. METHODS AND RESULTS: SHRcp rats were divided into (1) a renal
      denervation (RD) group and (2) a sham operation group (control) to examine the
      effects of long-term RD on blood pressure circadian rhythm, renal sodium
      retention-related molecules, the renin-angiotensin-aldosterone system, metabolic
      disorders, and organ injury. RD in SHRcp rats not only significantly reduced
      blood pressure but also normalized blood pressure circadian rhythm from the
      nondipper to the dipper type, and this improvement was associated with an
      increase in urinary sodium excretion and the suppression of renal Na(+)-Cl(-)
      cotransporter upregulation. RD significantly reduced plasma renin activity. RD
      significantly prevented cardiovascular remodeling and impairment of vascular
      endothelial function and attenuated cardiovascular oxidative stress. However, RD
      failed to ameliorate obesity, metabolic disorders, and renal injury and failed to
      reduce systemic sympathetic activity in SHRcp rats. CONCLUSIONS: By including the
      upregulation of the Na(+)-Cl(-) cotransporter, the renal sympathetic nerve is
      involved in the disruption of blood pressure circadian rhythm as well as
      hypertension in metabolic syndrome. Thus, RD seems to be a useful therapeutic
      strategy for hypertension with metabolic syndrome.

PMID- 23974907
TI  - Dobutamine stress echocardiography in patients undergoing orthotopic liver
      transplantation: a pooled analysis of accuracy, perioperative and long term
      cardiovascular prognosis.
AB  - Pre-transplant evaluation for orthotopic liver transplantation (OLT) commonly
      includes a cardiac evaluation using dobutamine stress echocardiography (DSE). We
      performed a quantitative systematic review assessing DSE's use in detecting
      coronary artery disease (CAD) and predicting perioperative and long term cardiac
      events in patients undergoing OLT. Published studies in pubmed were accessed
      using keyword searches and bibliographic review. Included studies evaluated the
      use of DSE in patients undergoing OLT, including its accuracy for detection of
      CAD, and in predicting perioperative and long term cardiac prognosis for both
      hard (myocardial infarction, cardiac death, cardiac arrest, and asystole) and
      soft cardiac events (all other events that were cardiovascular in nature). We
      calculated DSE's sensitivity, specificity, negative predictive value (NPV), and
      positive predictive value (PPV) in the above areas. We identified 7 studies,
      including a total of 580 patients, which included 4 accuracy studies (n = 110
      patients), 4 perioperative studies, and 3 long term studies. Accuracy for CAD
      included a sensitivity of 0.32, specificity of 0.78, PPV of 0.37, and NPV of
      0.75. Accuracy for prediction of perioperative hard and soft cardiac events was a
      sensitivity of 0.20 and 0, specificity of 0.99 and 0.99, PPV of 0.33 and 0, and
      NPV of 0.98 and 0.89, respectively. For long term hard and soft cardiac events,
      sensitivity was 0.5 and 0, specificity 0.99 and 0.98, PPV 0.33 and 0, and NPV
      0.99 and 0.96, respectively. DSE has a limited accuracy for the detection of CAD
      in candidates for OLT. However, among those patients selected for OLT, the
      negative predictive value of DSE for both perioperative and long term cardiac
      events is high. 

PMID- 23974906
TI  - Hypotension due to Kir6.1 gain-of-function in vascular smooth muscle.
AB  - BACKGROUND: KATP channels, assembled from pore-forming (Kir6.1 or Kir6.2) and
      regulatory (SUR1 or SUR2) subunits, link metabolism to excitability. Loss of
      Kir6.2 results in hypoglycemia and hyperinsulinemia, whereas loss of Kir6.1
      causes Prinzmetal angina-like symptoms in mice. Conversely, overactivity of
      Kir6.2 induces neonatal diabetes in mice and humans, but consequences of Kir6.1
      overactivity are unknown. METHODS AND RESULTS: We generated transgenic mice
      expressing wild-type (WT), ATP-insensitive Kir6.1 [Gly343Asp] (GD), and ATP
      insensitive Kir6.1 [Gly343Asp,Gln53Arg] (GD-QR) subunits, under Cre-recombinase
      control. Expression was induced in smooth muscle cells by crossing with smooth
      muscle myosin heavy chain promoter-driven tamoxifen-inducible Cre-recombinase
      (SMMHC-Cre-ER) mice. Three weeks after tamoxifen induction, we assessed blood
      pressure in anesthetized and conscious animals, as well as contractility of
      mesenteric artery smooth muscle and KATP currents in isolated mesenteric artery
      myocytes. Both systolic and diastolic blood pressures were significantly reduced
      in GD and GD-QR mice but normal in mice expressing the WT transgene and elevated
      in Kir6.1 knockout mice as well as in mice expressing dominant-negative Kir6.1
      [AAA] in smooth muscle. Contractile response of isolated GD-QR mesenteric
      arteries was blunted relative to WT controls, but nitroprusside relaxation was
      unaffected. Basal KATP conductance and pinacidil-activated conductance were
      elevated in GD but not in WT myocytes. CONCLUSIONS: KATP overactivity in vascular
      muscle can lead directly to reduced vascular contractility and lower blood
      pressure. We predict that gain of vascular KATP function in humans would lead to
      a chronic vasodilatory phenotype, as indeed has recently been demonstrated in
      Cantu syndrome.

PMID- 23974908
TI  - The diagnostic accuracy of pocket-size cardiac ultrasound performed by unselected
      residents with minimal training.
AB  - Pocket-size imaging devices may represent a tool for fast initial cardiac
      screening in the emergency setting. Pocket-size cardiac ultrasound (PCU)
      examinations performed by experienced echocardiographers yield acceptable
      diagnostic accuracy compared to standard echocardiogram (SE). However, the
      success of this method when used by unselected non-cardiologists remains
      unexplored. The current study studies the diagnostic accuracy of PCU when used by
      unselected internal medicine residents with minimal training. All residents were
      given a 2-hour introductory course in PCU (Vscan) and reported PCU results for up
      to 15 predefined cardiac landmarks. These were arbitrarily divided into 3
      priority groups, such that left ventricle (LV) and pericardium were of first
      priority. Diagnostic accuracy [sensitivity/specificity and negative/positive
      predictive values (PPV/NPV)] and agreement were evaluated using a subsequent SE
      as reference. During a 9.2 months period a total of 303 patients were included in
      the study, the majority on the basis of presenting with chest pain or suspected
      heart failure. In the pooled LV and pericardial (1st priority) data,
      sensitivity/specificity/PPV/NPV were 61/92/70/89% respectively. Similar
      specificities and NPVs were observed for the 11 remaining indices, as were lower
      sensitivities and PPVs. The best PCU sensitivity (76%) was attained for the
      assessment of LV wall motion abnormalities. Overall agreement was k = 0.50. PCU
      examination performed by internal medicine residents with minimal training could
      provide a suitable means of ruling out cardiac pathology, as reflected in the
      high specificities and NPVs. It is not, however, a satisfactory tool for
      identifying patients with various cardiac disorders.

PMID- 23974909
TI  - Determination of cardiac output with dynamic contrast-enhanced computed
      tomography.
AB  - Cardiac output (CO) is an important diagnostic and prognostic factor in the
      haemodynamic evaluation of patients. The gold standard for CO measurement,
      thermodilution, requires an invasive right-heart catheterisation (RHC). In this
      pilot study we aimed to determine the accuracy of non-invasive CO determination
      from dynamic contrast-enhanced computed tomography (CT) compared to
      thermodilution. Patients who underwent diagnostic or follow-up RHC due to
      suspected or known pulmonary vascular disease at our department and required a
      thoracic CT between June 2011 and August 2012 were included. CO was determined
      from CT attenuation-time curves in the pulmonary artery and the ascending aorta
      using a dynamic contrast-enhanced CT sequence. CO determined in N = 18 patients
      by dynamic CT in the pulmonary artery was in very good agreement with
      thermodilution data (r = 0.84). Bland-Altman analysis showed a systematic
      overestimation of 0.7 +/- 0.6 l/min compared to thermodilution. Data from the
      ascending aorta also showed a good correlation, but with a larger scattering of
      the values. The average effective dose for the dynamic investigation was 1.2 +/-
      0.7 mSv. CO determined with dynamic contrast-enhanced CT in the main pulmonary
      artery reliably predicts the values obtained by thermodilution during RHC. This
      non-invasive technique might provide an alternative for repeated invasive right
      heart catheter investigations in the follow-up of pulmonary arterial hypertension
      patients. 

PMID- 23974911
TI  - Arabidopsis HY1 confers cadmium tolerance by decreasing nitric oxide production
      and improving iron homeostasis.
AB  - Up-regulation of the gene that encodes intracellular heme oxygenase 1 (HO1)
      benefits plants under cadmium (Cd(2+)) stress; however, the molecular mechanisms
      remain unclear. Here, we elucidate the role of Arabidopsis HY1 (AtHO1) in Cd(2+)
      tolerance by using genetic and molecular approaches. Analysis of two HY1 null
      mutants, three HY1 overexpression lines, HO double or triple mutants, as well as
      phyA and phyB mutants revealed the specific hypersensitivity of hy1 to Cd(2+)
      stress. Supplementation with two enzymatic by-products of HY1, carbon monoxide
      (CO) and iron (Fe, especially), rescued the Cd(2+)-induced inhibition of primary
      root (PR) elongation in hy1-100. The mutation of HY1, which exhibited lower
      glutathione content than Col-0 in root tissues, was able to induce nitric oxide
      (NO) overproduction, Cd(2+) accumulation, and severe Fe deficiency in root
      tissues. However, the contrasting responses appeared in 35S:HY1-4. Additionally,
      reduced levels of Ferric Reduction Oxidase 2 (FRO2) and Iron-Regulated
      Transporter 1 (IRT1) transcripts, and increased levels of Heavy Metal ATPase 2/4
      (HMA2/4) transcripts bolster the notion that HY1 up-regulation ameliorates Fe
      deficiency, and might increase Cd(2+) exclusion. Taken together, these results
      showed that HY1 plays a common link in Cd(2+) tolerance by decreasing NO
      production and improving Fe homeostasis in Arabidopsis root tissues.

PMID- 23974910
TI  - Anti-endotoxin vaccines: back to the future.
AB  - Gram-negative bacterial (GNB) infections are a leading cause of serious
      infections both in hospitals and the community. The mortality remains high
      despite potent antimicrobials and modern supportive care. In the last decade
      invasive GNB have become increasingly resistant to commonly used antibiotics, and
      attempts to intervene with novel biological therapies have been unsuccessful.
      Earlier studies with antibodies directed against a highly conserved core region
      in the GNB lipopolysaccharide (LPS, or endotoxin) suggested that this approach
      may have therapeutic benefit, and led to the development of a subunit vaccine
      that has progressed to phase 1 clinical testing. Since only a few serogroups of
      GNB cause bacteremia, O-specific vaccines had been developed, but these were not
      deployed because of the availability of other therapeutic options at the time.
      Given the likelihood that new antibiotics will not be soon available, the
      development of vaccines and antibodies directed against endotoxin, both O and
      core antigens, deserves a "second look". 

PMID- 23974912
TI  - [Neutropenia and sepsis].
AB  - The clinical management of neutropenic infections represents a great diagnostic
      and therapeutic challenge. Established sepsis criteria only partially reflect the
      neutropenic setting. Diagnostic procedures are frequently impaired by
      thrombocytopenia and progressive respiratory insufficiency. Increased tendency to
      bleed, engraftment, and fulminant progression represent major therapeutic
      challenges. Thus, crucial for the diagnosis and therapy of neutropenic sepsis are
      clear and well-communicated algorithms, rapid action, and close collaboration
      between oncologists and intensivists. 

PMID- 23974913
TI  - [Thrombotic microangiopathy].
AB  - Thrombotic microangiopathy should be suspected every time the combination of
      microangiopathic hemolytic anemia without a coexisting cause, thrombocytopenia as
      well as renal and/or neurologic abnormalities occurs. The general term thrombotic
      microangiopathy includes different subtypes of the disease leading to
      abnormalities in multiple organ systems by endothelial injury and formation of
      platelet-rich thrombi in small vessels. The main types include thrombotic
      thrombocytopenic purpura in case of dominant neurologic abnormalities and the
      hemolytic uremic syndrome in case of acute kidney injury, respectively. Although
      these syndromes differ in their etiologies, clinical features, response to
      treatment, and prognosis, an early initiation of a direct therapeutic
      intervention frequently determines the clinical course of the patient.
      Irrespectively of the underlying etiology, plasma exchange is an essential
      component of acute therapeutic intervention while ongoing diagnostics are used to
      identify the definite treatment. 

PMID- 23974914
TI  - [Drug therapy of infectious diarrhea: part 1: acute diarrhea].
AB  - BACKGROUND: Diarrhea is one of the most commonly occurring diseases. AIM: This
      article gives a review of the current state of the treatment of acute infectious
      diarrhea (part 1) and chronic infectious diarrhea (part 2) as well as of the most
      important pathogens. MATERIAL AND METHODS: Following a presentation of the
      general principles of the therapy of diarrhea, the targeted antimicrobial therapy
      of the most important bacterial gastrointestinal infections is described. This
      includes salmonellosis, shigellosis and Campylobacter infections, infections with
      pathogenic Escherichia coli strains, yersiniosis and cholera. Due to the
      increasing incidence and changes in the severity of the disease and important new
      aspects in the treatment of diarrhea caused by toxigenic Clostridium difficile
      strains, these disease entities will be described in detail. RESULTS: Symptomatic
      therapy is still the most important aspect of the treatment of infectious
      diarrhea. For severely ill patients with a high frequency of stools (> 8/day),
      immunodeficiency, advanced age or significant comorbidities, empirical antibiotic
      therapy should be considered. Increasing resistance, in particular against
      fluoroquinolones must also be taken into consideration. Due to the risk of
      excessive pathogen proliferation and concomitant intestinal toxin production with
      protracted or multiple complications during the disease, therapy with motility
      inhibitors is not recommended. With respect to the treatment of Clostridium
      difficile infections a promising novel aspect arose in 2012. The macrocyclic
      antibiotic fidaxomycin can reduce the rate of recurrent disease with the same
      effectiveness as vancomycin. Furthermore, evidence for the benefits of allogenic
      stool transplantation is increasing. CONCLUSION: The treatment of acute diarrhea
      is still primarily supportive. The benefits of general empirical antibiotic
      therapy for acute diarrhea are not evidence-based.

PMID- 23974915
TI  - Patient-reported visual function outcomes improve after ranibizumab treatment in
      patients with vision impairment due to diabetic macular edema: randomized
      clinical trial.
AB  - IMPORTANCE: Few data are available on relative changes in vision-related function
      after treatment for diabetic macular edema (DME). OBJECTIVE: To determine the
      impact of intravitreal ranibizumab, 0.5 mg, compared with laser on patient
      reported visual function. DESIGN: Phase 3, randomized, double-masked, 12-month
      study (RESTORE). SETTING: Outpatient retina practices in Australia, Canada, and
      Europe. PARTICIPANTS: Patients 18 years or older with type 1 or 2 diabetes
      mellitus and visual impairment due to DME. INTERVENTIONS: Patients were
      randomized to ranibizumab plus sham laser (n = 116), ranibizumab plus laser (n =
      118), or sham injections plus laser (n = 111). Ranibizumab and sham injections
      were given for 3 consecutive months then as needed; laser or sham laser treatment
      was given at baseline then as needed. MAIN OUTCOMES AND MEASURES: National Eye
      Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) scores at 0, 3, and 12
      months for patients receiving 1 or more study treatments with 1 or more
      postbaseline NEI VFQ-25 assessments and last observation carried forward for
      missing data. RESULTS: Mean baseline NEI VFQ-25 composite scores were 72.8, 73.5,
      and 74.1 in the ranibizumab, laser, and ranibizumab plus laser groups,
      respectively. At 12 months, the mean composite scores (95% CIs) improved by 5.0
      (ranibizumab vs laser, 2.6 to 7.4; P = .01 vs laser) and 5.4 (ranibizumab plus
      laser vs laser alone, 3.3 to 7.4; P = .004 vs laser) from baseline in the
      ranibizumab and ranibizumab plus laser groups, respectively, compared with 0.6 (
      1.8 to 3.0) for the laser group. Near activities scores improved by 9.0
      (ranibizumab vs laser, 5.0 to 13.0; P = .01) and 9.1 (ranibizumab plus laser vs
      laser, 5.6 to 12.6; P = .006) compared with 1.1 (-3.0 to 5.2) for the laser
      group, whereas distance activities scores improved by 5.3 (ranibizumab vs laser,
      1.8 to 8.9; P = .04) and 5.6 (ranibizumab plus laser vs laser, 2.3 to 9.0; P =
      .03) compared with 0.4 (-3.1 to 3.8) for the laser group. Patients with better
      baseline visual acuity or lower central retinal thickness had greater
      improvements with ranibizumab treatment compared with laser in composite and some
      subscale scores compared with patients with worse visual acuity or higher central
      retinal thickness. CONCLUSIONS AND RELEVANCE: These data provide vision-related,
      patient-reported outcome evidence that mirrors visual acuity outcomes and
      supports benefits from ranibizumab or ranibizumab plus laser treatment for
      patients with DME and characteristics similar to those enrolled in this
      randomized clinical trial. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00687804.

PMID- 23974916
TI  - Perioperative management of delirium and dementia in the geriatric surgical
      patient.
AB  - BACKGROUND: Older adults undergo operations as our population ages. Increasing
      life expectancy and disease burden, along with decreased functional status and
      organ reserve, place the elderly surgical patient at higher general risk in the
      perioperative state. In particular, these patients have more diseases including
      dementia and medications that put them specifically at higher risk of delirium.
      PURPOSE: This overview describes the diagnosis, pathophysiology, and treatment of
      delirium and its interface with depression and dementia, and explains aging
      changes based on the picture of perioperative management in surgical
      interventions. CONCLUSIONS: Today, surgeons must be equipped to attend the
      geriatric patient's needs. Early recognition of comorbidities such as dementia
      and delirium as well as speedy and competent therapeutic treatment can limit
      consequences and impact.

PMID- 23974917
TI  - Comprehensive evaluation of indoor tanning regulations: a 50-state analysis,
      2012.
AB  - Teenage use of indoor tanning has reached epidemic proportions. There is no
      federal ban on teen use; rather, it is left to each state to determine policy. We
      conducted a state-by-state analysis using data from each state's statutes and
      regulations and supplementary information from the National Conference of State
      Legislatures. First, we refined an earlier 35-item instrument to now include 56
      items that extensively measures age bans, parental involvement,
      warnings/information, enforcement, and operating requirements. To grade each
      tanning law, we developed a uniform scoring system with a goal of providing
      performance data for future comparisons. As of August 2012, 13 states had no
      tanning facility statute or regulation for minors. In states with some
      regulations, teen bans are lax-nearly uniformly, most young children under the
      age of 14 can legally tan with or without suboptimal parental consent or
      accompaniment laws. Strong Food and Drug Administration involvement can simplify
      and unify the inconsistencies that exist among states' indoor tanning laws. Until
      consistent regulations are promulgated and enforced, such an instrument can
      provide a benchmark for state investigations into the deficiencies and progress
      of their laws, as well as facilitate direct comparison between states for
      research and educational purposes. 

PMID- 23974918
TI  - GAD65 autoantibodies detected by electrochemiluminescence assay identify high
      risk for type 1 diabetes.
AB  - The identification of diabetes-relevant islet autoantibodies is essential for
      predicting and preventing type 1 diabetes (T1D). The aim of the current study was
      to evaluate a newly developed electrochemiluminescence (ECL)-GAD antibody (GADA)
      assay and compare its sensitivity and disease relevance with standard radioassay.
      The assay was validated with serum samples from 227 newly diagnosed diabetic
      children; 68 prediabetic children who were prospectively followed to T1D; 130
      nondiabetic children with confirmed islet autoantibodies to insulin, GAD65, IA-2,
      and/or ZnT8 longitudinally followed for 12 +/- 3.7 years; and 181 age-matched,
      healthy, antibody-negative children. The ECL-GADA assay had a sensitivity similar
      to that of the standard GADA radioassay in children newly diagnosed with T1D,
      prediabetic children, and high-risk children with multiple positive islet
      autoantibodies. On the other hand, only 9 of 39 nondiabetic children with only a
      single islet autoantibody (GADA only) by radioassay were positive for ECL-GADA.
      GADA not detectable by ECL assay is shown to be of low affinity and likely not
      predictive of future diabetes. In conclusion, the new ECL assay identifies
      disease-relevant GADA by radioassay. It may help to improve the prediction and
      correct diagnosis of T1D among subjects positive only for GADA and no other islet
      autoantibodies. 

PMID- 23974919
TI  - Gestational diabetes mellitus impairs Nrf2-mediated adaptive antioxidant defenses
      and redox signaling in fetal endothelial cells in utero.
AB  - In utero exposure to gestational diabetes mellitus (GDM) is associated with an
      increased risk of type 2 diabetes and cardiovascular disease in later life, yet
      the underlying mechanisms remain to be elucidated. We examined the effects of GDM
      on the proteome, redox status, and nuclear factor erythroid 2-related factor 2
      (Nrf2)-mediated antioxidant gene expression in human fetal endothelial cells.
      Proteomic analysis revealed that proteins involved in redox homeostasis were
      significantly altered in GDM and associated with increased mitochondrial
      superoxide generation, protein oxidation, DNA damage, and diminished glutathione
      (GSH) synthesis. In GDM cells, the lipid peroxidation product 4-hydroxynonenal
      (HNE) failed to induce nuclear Nrf2 accumulation and mRNA and/or protein
      expression of Nrf2 and its target genes NAD(P)H:quinone oxidoreductase 1 (NQO1),
      Bach1, cystine/glutamate transporter, and glutamate cysteine ligase. Although
      methylation of CpG islands in Nrf2 or NQO1 promoters was unaltered by GDM,
      decreased DJ-1 and increased phosphorylated glycogen synthase kinase 3beta levels
      may account for impaired Nrf2 signaling. HNE-induced increases in GSH and NQO1
      levels were abrogated by Nrf2 small interfering RNA in normal cells, and
      overexpression of Nrf2 in GDM cells partially restored NQO1 induction.
      Dysregulation of Nrf2 in fetal endothelium may contribute to the increased risk
      of type 2 diabetes and cardiovascular disease in offspring. 

PMID- 23974920
TI  - Mitochondrial respiratory capacity and content are normal in young insulin
      resistant obese humans.
AB  - Considerable debate exists about whether alterations in mitochondrial respiratory
      capacity and/or content play a causal role in the development of insulin
      resistance during obesity. The current study was undertaken to determine whether
      such alterations are present during the initial stages of insulin resistance in
      humans. Young (~23 years) insulin-sensitive lean and insulin-resistant obese men
      and women were studied. Insulin resistance was confirmed through an intravenous
      glucose tolerance test. Measures of mitochondrial respiratory capacity and
      content as well as H(2)O(2) emitting potential and the cellular redox environment
      were performed in permeabilized myofibers and primary myotubes prepared from
      vastus lateralis muscle biopsy specimens. No differences in mitochondrial
      respiratory function or content were observed between lean and obese subjects,
      despite elevations in H(2)O(2) emission rates and reductions in cellular
      glutathione. These findings were apparent in permeabilized myofibers as well as
      in primary myotubes. The results suggest that reductions in mitochondrial
      respiratory capacity and content are not required for the initial manifestation
      of peripheral insulin resistance.

PMID- 23974921
TI  - Coxsackievirus B1 is associated with induction of beta-cell autoimmunity that
      portends type 1 diabetes.
AB  - The rapidly increasing incidence of type 1 diabetes implies that environmental
      factors are involved in the pathogenesis. Enteroviruses are among the suspected
      environmental triggers of the disease, and the interest in exploring the
      possibilities to develop vaccines against these viruses has increased. Our
      objective was to identify enterovirus serotypes that could be involved in the
      initiation of the disease process by screening neutralizing antibodies against 41
      different enterovirus types in a unique longitudinal sample series from a large
      prospective birth-cohort study. The study participants comprised 183 case
      children testing persistently positive for at least two diabetes-predictive
      autoantibodies and 366 autoantibody-negative matched control children.
      Coxsackievirus B1 was associated with an increased risk of beta-cell
      autoimmunity. This risk was strongest when infection occurred a few months before
      autoantibodies appeared and was attenuated by the presence of maternal antibodies
      against the virus. Two other coxsackieviruses, B3 and B6, were associated with a
      reduced risk, with an interaction pattern, suggesting immunological cross
      protection against coxsackievirus B1. These results support previous observations
      suggesting that the group B coxsackieviruses are associated with the risk of type
      1 diabetes. The clustering of the risk and protective viruses to this narrow
      phylogenetic lineage supports the biological plausibility of this phenomenon. 

PMID- 23974922
TI  - Conditional hypovascularization and hypoxia in islets do not overtly influence
      adult beta-cell mass or function.
AB  - It is generally accepted that vascularization and oxygenation of pancreatic
      islets are essential for the maintenance of an optimal beta-cell mass and
      function and that signaling by vascular endothelial growth factor (VEGF) is
      crucial for pancreas development, insulin gene expression/secretion, and
      (compensatory) beta-cell proliferation. A novel mouse model was designed to allow
      conditional production of human sFlt1 by beta-cells in order to trap VEGF and
      study the effect of time-dependent inhibition of VEGF signaling on adult beta
      cell fate and metabolism. Secretion of sFlt1 by adult beta-cells resulted in a
      rapid regression of blood vessels and hypoxia within the islets. Besides blunted
      insulin release, beta-cells displayed a remarkable capacity for coping with these
      presumed unfavorable conditions: even after prolonged periods of blood vessel
      ablation, basal and stimulated blood glucose levels were only slightly increased,
      while beta-cell proliferation and mass remained unaffected. Moreover, ablation of
      blood vessels did not prevent beta-cell generation after severe pancreas injury
      by partial pancreatic duct ligation or partial pancreatectomy. Our data thus
      argue against a major role of blood vessels to preserve adult beta-cell
      generation and function, restricting their importance to facilitating rapid and
      adequate insulin delivery. 

PMID- 23974923
TI  - Peroxynitrite-dependent zinc release and inactivation of guanosine 5'
      triphosphate cyclohydrolase 1 instigate its ubiquitination in diabetes.
AB  - Aberrant degradation of guanosine 5'-triphosphate cyclohydrolase 1 (GTPCH1) with
      consequent deficiency of tetrahydrobiopterin is considered the primary cause for
      endothelial dysfunction in diabetes. How GTPCH1 becomes susceptible to the
      degradation remains unknown. We hypothesized that oxidation and release of the
      zinc ion by peroxynitrite (ONOO(-)), a potent oxidant generated by nitric oxide
      and superoxide anions, instigates GTPCH1 ubiquitination and degradation. Zinc
      contents, GTPCH1 ubiquitination, and GTPCH1 activity were assayed in purified
      GTPCH1, endothelial cells, and hearts from diabetic mice. Exogenous ONOO(-) dose
      dependently released zinc, inhibited its activity, and increased the ubiquitin
      binding affinity of GTPCH1 in vitro and in endothelial cells. Consistently, high
      glucose (30 mmol/L) inhibited GTPCH1 activity with increased ubiquitination,
      which was inhibited by antioxidants. Furthermore, mutation of the zinc-binding
      cysteine (141) (C141R or C141A) significantly reduced GTPCH1 activity and reduced
      its half-life but increased GTPCH1 ubiquitination, indicating an essential role
      of the zinc ion in maintaining the catalytic activity and stability of GTPCH1.
      Finally, GTPCH1 ubiquitination and degradation markedly increased in parallel
      with decreased GTPCH1 activity in the aortas and hearts of diabetic mice, both of
      which were attenuated by the inhibitors of ONOO(-) in mice in vivo. Taken
      together, we conclude that ONOO(-) releases zinc and inhibits GTPCH1, resulting
      in its ubiquitination and degradation of the enzyme. 

PMID- 23974924
TI  - Increased persistent sodium current due to decreased PI3K signaling contributes
      to QT prolongation in the diabetic heart.
AB  - Diabetes is an independent risk factor for sudden cardiac death and ventricular
      arrhythmia complications of acute coronary syndrome. Prolongation of the QT
      interval on the electrocardiogram is also a risk factor for arrhythmias and
      sudden death, and the increased prevalence of QT prolongation is an independent
      risk factor for cardiovascular death in diabetic patients. The pathophysiological
      mechanisms responsible for this lethal complication are poorly understood.
      Diabetes is associated with a reduction in phosphoinositide 3-kinase (PI3K)
      signaling, which regulates the action potential duration (APD) of individual
      myocytes and thus the QT interval by altering multiple ion currents, including
      the persistent sodium current INaP. Here, we report a mechanism for diabetes
      induced QT prolongation that involves an increase in INaP caused by defective
      PI3K signaling. Cardiac myocytes of mice with type 1 or type 2 diabetes exhibited
      an increase in APD that was reversed by expression of constitutively active PI3K
      or intracellular infusion of phosphatidylinositol 3,4,5-trisphosphate (PIP3), the
      second messenger produced by PI3K. The diabetic myocytes also showed an increase
      in INaP that was reversed by activated PI3K or PIP3. The increases in APD and
      INaP in myocytes translated into QT interval prolongation for both types of
      diabetic mice. The long QT interval of type 1 diabetic hearts was shortened by
      insulin treatment ex vivo, and this effect was blocked by a PI3K inhibitor.
      Treatment of both types of diabetic mouse hearts with an INaP blocker also
      shortened the QT interval. These results indicate that downregulation of cardiac
      PI3K signaling in diabetes prolongs the QT interval at least in part by causing
      an increase in INaP. This mechanism may explain why the diabetic population has
      an increased risk of life-threatening arrhythmias. 

PMID- 23974925
TI  - Lower "awake and fed thermogenesis" predicts future weight gain in subjects with
      abdominal adiposity.
AB  - Awake and fed thermogenesis (AFT) is the energy expenditure (EE) of the nonactive
      fed condition above the minimum metabolic requirement during sleep and is
      composed of the thermic effect of food and the cost of being awake. AFT was
      estimated from whole-room 24-h EE measures in 509 healthy subjects (368 Native
      Americans and 141 whites) while subjects consumed a eucaloric diet. Follow-up
      data were available for 290 Native Americans (median follow-up time: 6.6 years).
      AFT accounted for ~10% of 24-h EE and explained a significant portion of
      deviations from expected energy requirements. Energy intake was the major
      determinant of AFT. AFT, normalized as a percentage of intake, was inversely
      related to age and fasting glucose concentration and showed a nonlinear
      relationship with waist circumference and BMI. Spline analysis demonstrated that
      AFT becomes inversely related to BMI at an inflection point of 29 kg/m(2). The
      residual variance of AFT, after accounting for covariates, predicted future
      weight change only in subjects with a BMI >29 kg/m(2). AFT may influence daily
      energy balance, is reduced in obese individuals, and predicts future weight gain
      in these subjects. Once central adiposity develops, a blunting of AFT may occur
      that then contributes to further weight gain.

PMID- 23974926
TI  - Gene targeting in NOD mouse embryos using zinc-finger nucleases.
AB  - Studies in NOD mice have provided important insight into the genetics and
      pathogenesis of type 1 diabetes (T1D). Our goal was to further explore novel
      methods of genetic manipulation in this mouse model. We tested the feasibility of
      using zinc-finger nucleases (ZFNs) to knock out a gene directly in a pure NOD
      background, bypassing the need of embryonic stem cells. We report here the
      successful application of ZFN pairs to specifically and efficiently knock out
      Tnfrsf9 (encoding CD137/4-1BB) directly in the NOD mouse by embryo
      microinjection. Histology and T1D incidence studies indicated that CD137 was
      dispensable for the development of insulitis but played a role to promote
      progression to overt diabetes in NOD mice. We also demonstrated that CD137
      deficient T-cells were less diabetogenic than their wild-type counterpart when
      adoptively transferred into NOD.Rag1(-/-) recipients, even when CD25(+) cells
      were predepleted. In vitro assays suggested that CD137 deficiency had a limited
      effect on the suppressive function of CD4(+)CD25(+) regulatory T-cells (Tregs).
      Therefore, CD137 deficiency predominately affected effector T-cells rather than
      Tregs. Our study demonstrates the ability to generate gene-targeted knockouts in
      a pure NOD background by using ZFNs without potential confounding factors
      introduced by contaminating genetic materials obtained from other strains. 

PMID- 23974927
TI  - No detectable precolostral antibody response in calves born from cows with
      cotyledons positive for Coxiella burnetii by quantitative PCR.
AB  - Samples from 45 dams (milk/colostrum, faeces, vaginal fluid and blood on days 171
      177 of gestation and at parturition, and cotyledons at parturition) and their
      calves (blood collected before colostrum intake and weekly until days 29-35) were
      analysed to examine the vertical transmission of Coxiella burnetii and links
      between shedding and seropositivity. All calves were born C. burnetii
      seronegative. Only those born to seropositive dams seroconverted following
      colostrum intake. Logistic regression analyses indicated that the likelihood of
      dam seropositivity was 21 and 4.85 times higher for multiparous than for
      primiparous (65.6% vs. 8.3%, P = 0.006) and for prepartum shedding cows (75% vs.
      38.2%, P = 0.03) compared to the remaining animals, respectively. In conclusion,
      the results of this study indicate no detectable precolostral antibody response
      in calves born from dams with cotyledons positive for C. burnetii by qPCR. In
      order to analyse the possibility of persistent infection due to immunotolerance
      to an early in utero infection, further studies will need to test for C. burnetii
      DNA. In addition, in the present study multiparous cows showed a significantly
      higher seroprevalence than primiparous cows and heifers, colostral antibodies
      were efficiently transferred to newborn calves, and there was a link between
      bacterial shedding on days 171-177 of gestation and Coxiella seropositivity of
      the dam. 

PMID- 23974928
TI  - Tissue distribution of human and avian type sialic acid influenza virus receptors
      in domestic cat.
AB  - Infection of host cells with the influenza virus is mediated by specific
      interactions between the viral haemagglutinin (HA) and cell oligosaccharides
      containing sialic acid (SA) residues. Avian and human influenza viruses bind to
      alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors, respectively. To date,
      there have been no detailed tissue distribution data on alpha-2, 3 and alpha-2, 6
      sialic acid-linked receptors in the domestic cat, a relatively new mammalian host
      for influenza virus infections. In this study, the tissue distribution of human
      and avian type sialic acid influenza receptors was determined in various organs
      (respiratory tract, gastrointestinal tract, brain, cerebellum, spleen, kidney,
      heart and pancreas) of domestic cat by binding with the lectins Maackia amurensis
      agglutinin II (MAA II) and Sambucus nigra agglutinin (SNA), respectively. The
      results revealed that both alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors
      were extensively detected in the trachea, bronchus, lung, kidney, spleen,
      pancreas and gastrointestinal tract. Endothelial cells of gastrointestinal tract
      organs were negative for alpha-2, 3 sialic acid-linked receptors in cats. The
      presence of alpha-2, 3 and alpha-2, 6 sialic acid-linked receptors in the major
      organs examined in the present study suggests that each major organ may be
      affected by influenza virus infection. Because of receptor distribution in the
      gastrointestinal tract, the experimental infection of cats with human influenza
      virus may be relatively easy while their infection with avian influenza virus may
      be difficult. These data can explain the involvement of multiple organs in
      influenza virus infection and should help investigators interpret the results
      obtained when cats are infected with influenza virus and estimate the risk of
      infection between cats and humans. 

PMID- 23974929
TI  - Retrospective study of bull semen quality - possible correlation with pesticide
      use?
AB  - Decline in semen quality in humans and increased incidence of male reproductive
      problems could be caused by different factors, including pesticides that could
      mimic or block the action of endogenous hormones. If the decline in semen quality
      is real, and environmental chemicals are at least partially responsible for this
      decline, similar changes should be observed in animals that live in close
      connection with humans and are exposed to similar levels of pollutants. In the
      present study, the semen quality of bulls in the last 30 years was examined with
      respect to the year of birth. Furthermore, semen quality results were correlated
      to the total pesticide use in a limited geographical area. The results indicate a
      notable decrease in both ejaculate volume and total number of spermatozoa in
      ejaculates of bulls born in the late 1970s, while after that (until 2006) there
      was no obvious downward or upward trend either in ejaculate volume or in the
      total number of sperm cells. The amount of pesticides released into the
      environment increased about twofold in the given period, and linear regression
      analysis revealed a strong and statistically significant correlation between the
      amount of pesticides used and the total number of spermatozoa in the ejaculate. 

PMID- 23974930
TI  - Differential diagnosis of Moniezia benedeni and M. expansa (Anoplocephalidae) by
      PCR using markers in small ribosomal DNA (18S rDNA).
AB  - Moniezia benedeni and M. expansa are common ruminant tapeworms of worldwide
      distribution, causing gastrointestinal disorders and even death in sheep and
      goats. In this study, a polymerase chain reaction- (PCR-) based approach for
      precise species identification was developed and also applied to faecal DNA
      diagnosis of the tapeworm infection. Since nuclear ribosomal DNA (rDNA) appears
      to be a useful target for species and/or strain markers, the 18S regions of the
      rDNA of M. benedeni and M. expansa were amplified and sequenced. The lengths and
      GC contents of the regions sequenced were 2476-2487 bp and 51.9-52.1% for M.
      benedeni and 2473 bp and 51.9-52.0% for M. expansa, respectively. Alignment and
      comparison of the 18S sequences of the two species showed 92.5-93.3% homology. No
      matches for the 18S regions of M. benedeni and M. expansa were found with other
      species by BLAST search, which made the 18S sequences appropriate markers for the
      design of distinctive primers for the two Moniezia species. Our 18S-based PCR
      could detect as low levels as 0.5 pg genomic DNA or the DNA extracted from 0.2 g
      faecal sample collected from the rectum of an M. expansa-infected goat. The
      results indicate that this PCR approach is a reliable alternative for the
      differential diagnosis of Moniezia species in faecal samples. 

PMID- 23974931
TI  - Validation of housekeeping genes for studying differential gene expression in the
      bovine myometrium.
AB  - The aim of this study was to determine the steady-state expression of 13 selected
      housekeeping genes in the myometrium of cyclic and pregnant cows. Cells taken
      from bovine myometrium on days 1-5, 6-10, 11-16 and 17-20 of the oestrous cycle
      and in weeks 3-5, 6-8 and 9-12 of pregnancy were used. Reverse transcribed RNA
      was amplified in real-time PCR using designed primers. Reaction efficiency was
      determined with the Linreg programme. The geNorm and NormFinder programmes were
      used to select the best housekeeping genes. They calculate the expression
      stability factor for each used housekeeping gene with the smallest value for most
      stably expressed genes. According to geNorm, the most stable housekeeping genes
      in the myometrium were C2orf29, TPB and TUBB2B, while the least stably expressed
      genes were 18S RNA, HPRT1 and GAPDH. NormFinder identified the best genes in the
      myometrium as C2orf29, MRPL12 and TBP, while the worst genes were 18S RNA, B2M
      and SF3A1. Differences in stability factors between the two programmes may also
      indicate that the physiological status of the female, e.g. pregnancy, affects the
      stability of expression of housekeeping genes. The different expression stability
      of housekeeping genes did not affect progesterone receptor expression but it
      could be important if small differences in gene expression were measured between
      studies. 

PMID- 23974932
TI  - Mixed infection by fowlpox virus and Chlamydophila psittaci in a commercial
      laying hen flock.
AB  - An outbreak of fowlpox occurred in a commercial laying hen flock in one of the
      western provinces of Poland. Clinical signs suggested fowlpox and the diagnosis
      was confirmed by histopathological detection of Bollinger bodies within the
      epithelial cells. Detailed ultrastructural examination revealed an additional
      concurrent infection with chlamydia-like particles. The particles were identified
      by PCR as fowlpox virus and Chlamydophila psittaci. It is worth noting that both
      pathogens can generate morphologic forms capable of prolonged survival and
      inducing latent and persistent infection. We suggest a possible interaction
      between the two pathogens on ultrastructural level and assess the clinical
      consequences of the mixed infection. This study also demonstrates a potential of
      the transmission electron microscope (TEM) for identifying a superinfection with
      another pathogen (in this case C. psittaci), which may remain undetected by
      routine techniques. 

PMID- 23974933
TI  - Comparison of activation ability between feline and bovine oocytes.
AB  - Research comparing the activation sensitivity of oocytes to chemical treatment
      among mammalian species remains limited. We compared the activation ability of
      oocytes from bovine and feline ovaries when treated with ethanol alone, with
      ethanol and cycloheximide, and without any chemical treatment; the oocytes were
      then cultured for 72 h. After in vitro maturation (IVM), 5% of feline oocytes
      were activated and 1% were cleaved, whereas there were no prematurely activated
      bovine oocytes. Activation rates with ethanol and ethanol/cycloheximide were
      significantly higher (P < 0.01) in bovine oocytes than in feline oocytes (74.2%
      vs. 34.1% and 86.3% vs. 52.5%, respectively). Thus, our findings indicate that
      feline oocytes can be prematurely activated by the end of IVM, and that bovine
      oocytes may have a higher sensitivity of parthenogenetic activation to chemical
      treatment than do feline oocytes. 

PMID- 23974934
TI  - Identification of common, non-typable and autoagglutinating Salmonella strains
      with Premi(r)Test Salmonella assay.
AB  - Since Salmonella serotyping according to the White-Kauffmann-Le Minor scheme
      fails to identify rough and atypical serological variants, this study aimed at
      improving serovar identification with the commercially available Premi(r)Test
      Salmonella Assay. The array was validated against a set of Salmonella reference
      strains (n = 27) and field isolates of known serological structure (n = 112)
      showing up to 97.8% congruent results. Its diagnostic suitability was further
      verified with random field isolates (n = 52; 100% congruence). For 'rough'
      isolates (n = 54) and those with antigen expression failure (n = 19) the assay
      showed, respectively, 98.1% and 73.7% of serovar recognition. It considerably
      improved diagnostic capacity while typing troublesome isolates such as those
      failing to express flagellar antigens or showing autoagglutination. The method
      offers lower labour time compared to the traditional serotyping and does not
      require a broad range of diagnostic sera. 

PMID- 23974935
TI  - Detection of porcine circovirus type 2 (PCV2) and porcine reproductive and
      respiratory syndrome virus (PRRSV) antibodies in meat juice samples from Polish
      wild boar (Sus scrofa L.).
AB  - PCV2 and PRRSV are two important pathogens of domestic swine. There is
      considerable evidence that the infection is also present in wild boars. Meat
      juice provides an alternative to serum for antibody testing, and it has been used
      in testing for many important porcine infectious diseases. Samples of brachial
      muscle were collected from 142 wild boars shot in different regions of Poland
      during the 2006/2007 and 2007/2008 hunting seasons. Meat juice harvested from
      muscle samples was tested using an ELISA test specific for PCV2 and PRRSV
      antibodies. Additionally, IgG and IgM antibodies specific for PCV2 were detected
      in order to estimate the status of the PCV2 infection. Only one of the tested
      meat juice samples was positive for PRRSV (0.7%), and 68 out of 142 (47.9%)
      samples were positive for PCV2. Of the positive animals, 4 (2.8%) had an antibody
      profile suggesting active infection, 2 (1.4%) early active infection, and 62
      (43.7%) late infection. Also, a lack of association between the age of the
      animals and the presence of antibodies related to the infection was noticed. 

PMID- 23974936
TI  - First description of hypospadias and inguinal bilateral cryptorchidism in mouflon
      (Ovis Gmelini Musimon) - short communication.
AB  - A mouflon showing severe weight loss and cachexia was examined. The animal had
      horns and a male-like body frame but the preputial fur was missing. The scrotum
      was completely absent. Both testicles were located next to the inguinal canal
      under the skin, and appeared only slightly smaller than normal. The prepuce was
      located in a perianal position under the anus and it resembled a vulva. The penis
      was underdeveloped and curled up inside the prepuce like an enlarged clitoris.
      The bulbourethral region and the urinary bladder looked normal. The orifice of
      the urethra was located in its normal position, but the glans penis appeared
      deformed. Microscopic examination of the testicles revealed mild degeneration of
      the seminiferous tubules and a marked proliferation of the interstitial
      connective tissue with Leydig cells still present. There were no marked changes
      in the bulbar part of the penis but the apical part exhibited marked interstitial
      fibrosis. This is the first description of hypospadias and cryptorchidism in
      mouflon. 

PMID- 23974937
TI  - Epigenetic effects of dietary butyrate on hepatic histone acetylation and enzymes
      of biotransformation in chicken.
AB  - The aim of the study was to investigate the in vivo epigenetic influences of
      dietary butyrate supplementation on the acetylation state of core histones and
      the activity of drug-metabolising microsomal cytochrome P450 (CYP) enzymes in the
      liver of broiler chickens in the starter period. One-day-old Ross 308 broilers
      were fed a starter diet without or with sodium butyrate (1.5 g/kg feed) for 21
      days. After slaughtering, nucleus and microsome fractions were isolated from the
      exsanguinated liver by multi-step differential centrifugation. Histone
      acetylation level was detected from hepatocyte nuclei by Western blotting, while
      microsomal CYP activity was examined by specific enzyme assays. Hyperacetylation
      of hepatic histone H2A at lysine 5 was observed after butyrate supplementation,
      providing modifications in the epigenetic regulation of cell function. No
      significant changes could be found in the acetylation state of the other core
      histones at the acetylation sites examined. Furthermore, butyrate did not cause
      any changes in the drugmetabolising activity of hepatic microsomal CYP2H and
      CYP3A37 enzymes, which are mainly involved in the biotransformation of most
      xenobiotics in chicken. These data indicate that supplementation of the diet with
      butyrate probably does not have any pharmacokinetic interactions with
      simultaneously applied xenobiotics. 

PMID- 23974938
TI  - Oral immunogenicity of a plant virus vector based porcine circovirus antigen -
      short communication.
AB  - A recombinant cucumber mosaic virus based expression system has been developed
      for the production of an immunogenic porcine circovirus epitope. The resulting
      nanoparticle was shown to elicit specific immune response in mice and pigs, when
      administered parenterally. To evaluate the oral applicability of this vaccine
      candidate, two experiments were performed. In the first one, the resistance of
      the vector itself to mucosal environment was tested in mice. Cucumber mosaic
      virus particles fed to mice were able to elicit specific mucosal and serum
      antibody production. In the second experiment, recombinant cucumber mosaic virus
      fed to piglets resulted in the appearance of porcine circovirus specific serum
      antibodies. The vector proved to be able to survive in the gastrointestinal
      tract, so that an epitope expressed on its surface could induce specific immune
      response. These results indicate that the developed plant virus based expression
      system offers an effective method for mucosal vaccine production. 

PMID- 23974939
TI  - Cardiac troponin I in healthy newborn goat kids and in goat kids with cardiac
      nutritional muscular dystrophy.
AB  - This study was designed to establish serum cardiac troponin I (cTnI)
      concentrations in healthy newborn goat kids and in those with cardiac nutritional
      muscular dystrophy (NMD). Thirty-five single full-term newborn goat kids (20
      males and 15 females; age: 6.1 +/- 3.5 h; weight 3.4 +/- 0.68 kg), together with
      their respective mothers (Group 1; G1) were enrolled consecutively. Thirty-one
      goat kids (age: 9.5 +/- 4.3 days) with NMD, together with 20 control goat kids
      (age: 7.8 +/- 4.3 days) were also included in this study (Group 2; G2). Blood
      samples were collected from G1 within 12 h of birth and from G2 on admission.
      Serum samples were collected and analysed for cTnI. In G1, the mean serum
      concentration of cTnI in goat kids was 0.290 +/- 0.37 ng/mL, with no
      statistically significant difference between male and female kids (P = 0.61). The
      mean cTnI concentration in the does was 0.017 +/- 0.04, ng/mL. Serum values of
      cTnI in the goat kids and in their respective mothers differed significantly (P =
      0.0001). In G2, the mean cTnI concentration was 0.02 +/- 0.05 ng/mL in the
      control and 11.18 +/- 20.07 ng/mL in the diseased goat kids, with a statistically
      significant difference between diseased and control goat kids (P = 0.017). Serum
      concentrations of cTnI are higher in goat kids than in their respective mothers.
      In conclusion, the cTnI assay appears to be a sensitive and specific marker for
      myocardial injury in goat kids. 

PMID- 23974940
TI  - Detection and characterisation of hepatitis E virus in naturally infected swine
      in Croatia.
AB  - Hepatitis E is a viral zoonotic disease infecting swine worldwide. Since pigs
      represent a likely animal reservoir for the hepatitis E virus, the epidemiology
      of naturally occurring hepatitis E was investigated in Croatian swine herds.
      Nearly all tested animals were seropositive for antibodies against the hepatitis
      E virus (55/60, 91.7%). Active infection was detected in all age groups by RT-PCR
      of viral RNA in serum (8/60, 13.3%) and bile samples (3/37, 8.1%), which was
      further confirmed by histopathological findings of characteristic lesions in the
      livers of the infected animals. Three new strains of hepatitis E virus were
      isolated from Croatian pig herds. Phylogenetic analysis using median-joining
      networks clustered those Croatian strains with isolates from various parts of the
      world, indicating their likely origin in international trade. Similarity to human
      isolates implies a zoonotic potential of Croatian strains, which raises a public
      health concern, especially in the light of the high prevalence of hepatitis E in
      the herds studied. 

PMID- 23974941
TI  - Sporadic re-emergence of enzootic porcine transmissible gastroenteritis in
      Hungary.
AB  - Transmissible gastroenteritis (TGE) is a coronavirus-induced disease of pigs,
      characterised by diarrhoea and vomiting. The incidence of the disease had been
      decreasing since the late 1980s when deletion mutant variants (porcine
      respiratory coronavirus, PRCoV) of the virus emerged, repressing TGE gradually.
      Although disease manifestations are infrequent, the virus is still present in pig
      herds, causing sporadic outbreaks in a milder form. Identification and
      characterisation of the spike genes from TGEV and PRCoV, detected in such
      outbreaks, were performed in Hungary. Analysis of the amplified partial gene
      sequences showed that TGEV was present in herds with TGE clinical signs together
      with PRCoV. The sequences, apart from the deletions in PRCoV, were identical and
      at least two types of PRCoV spike proteins could be identified based on the
      length of the deleted sequence. 

PMID- 23974942
TI  - Intestinal parasites of the red fox (Vulpes vulpes) in Slovenia.
AB  - In the present study, 428 foxes were collected and examined for intestinal
      helminths using the washing-out method. Parasites were found in 93.2% of the
      examined animals. The most frequently identified nematodes were Uncinaria
      stenocephala (58.9%), Toxocara canis (38.3%) and Molineus patens (30.6%). Other
      nematodes found were Pterygodermatites affinis (4.2%), Capillaria sp. (2.8%),
      Crenosoma vulpis (2.8%), Toxascaris leonina (2.5%), Trichuris vulpis (0.7%) and
      Physaloptera sp. (0.2%). Mesocestoides sp. (27.6%) and Taenia crassiceps (22.2%)
      were the most prevalent cestodes, followed by T. polyacantha (6.5%), Hymenolepis
      nana (2.1%), T. pisiformis (2.1%) and Dipylidium caninum (1.4%). The study also
      revealed four trematode species: Rossicotrema donicum (1.6%), Heterophyes
      heterophyes (1.1%), Metagonimus yokogawai (1.1%), Prohemistomum appendiculatum
      (0.4%) and two protozoan species: oocysts of Sarcocystis (2.8%) and Isospora
      (0.4%). This is the first extensive study on the intestinal parasites of the red
      fox (Vulpes vulpes) in Slovenia. The 2.6% prevalence of Echinococcus
      multilocularis in the same sample population as investigated herein has been
      reported previously (Vergles Rataj et al., 2010). 

PMID- 23974944
TI  - Brisk walking can promote functional recovery in chronic stroke patients.
AB  - OBJECTIVE: To determine whether regular brisk walking can promote functional
      recovery in community-dwelling stroke patients. PATIENTS: A total of 44 chronic
      stroke patients, recruited in Belgium and Benin, respectively European high
      income and African low-income countries. METHODS: This longitudinal, single
      cohort, observational study with 1 intervention period and 4 time-points of
      assessments (2 baseline, 1 post-intervention and 1 follow-up) was structured in 3
      periods: pre-intervention period (1 month), intervention period (3 months) and
      follow-up period (3 month). Intervention consisted of a 3 times/week group-based
      brisk walking programme. Primary outcome measures were ACTIVLIM-Stroke
      questionnaire and the 6-minute walk test (6MWT). Secondary outcome measures were
      the Stroke Impairment Assessment Set (SIAS), the Hospital Anxiety and Depression
      Scale (HADS), and the Berg Balance Scale (BBS). RESULTS: All outcome measures
      were stable during the pre-intervention period (p >= 0.16). They all improved
      significantly after intervention (p <= 0.01), except the HADS (p = 0.058).
      However, during the follow-up period, SIAS (p = 0.002) and BBS (p = 0.001)
      decreased, while ACTIVLIM-Stroke, 6MWT and HADS showed no significant change (p
      >= 0.13). CONCLUSION: This study suggests regular brisk walking as an effective
      approach to promote functional recovery in chronic stroke survivors. However,
      further studies are required before generalizing these results to the whole
      stroke population.

PMID- 23974943
TI  - Efficacy and safety of aspirin, clopidogrel, and warfarin after coronary artery
      stenting in Korean patients with atrial fibrillation.
AB  - There are limited data on the optimal antithrombotic therapy for patients with
      atrial fibrillation (AF) who undergoing coronary stenting. We reviewed 203
      patients (62.6 % men, mean age 68.3 +/- 10.1 years) between 2003 and 2012, and
      recorded clinical and demographic characteristics of the patients. Clinical
      follow-up included major adverse cardiac and cerebrovascular events (MACCE)
      (cardiac death, myocardial infarction, target lesion revascularization, and
      stroke), stent thrombosis, and bleeding. The most commonly associated
      comorbidities were hypertension (70.4 %), diabetes mellitus (35.5 %), and
      congestive heart failure (26.6 %). Sixty-three percent of patients had stroke
      risk higher than CHADS2 score 2. At discharge, dual-antiplatelet therapy
      (aspirin, clopidogrel) was used in 166 patients (81.8 %; Group I), whereas 37
      patients (18.2 %) were discharged with triple therapy (aspirin, clopidogrel,
      warfarin; Group II). The mean follow-up period was 42.0 +/- 29.0 months. The mean
      international normalized ratio (INR) in group II was 1.83 +/- 0.41. The total
      MACCE was 16.3 %, with stroke in 3.4 %. Compared with the group II, the incidence
      of MACCE (2.7 % vs 19.3 %, P = 0.012) and cardiac death (0 % vs 11.4 %, P =
      0.028) were higher in the group I. Major and any bleeding, however, did not
      differ between the two groups. In multivariate analysis, no warfarin therapy
      (odds ratio 7.8, 95 % confidence interval 1.02-59.35; P = 0.048) was an
      independent predictor of MACCE. By Kaplan-Meier survival analysis, warfarin
      therapy was associated with a lower risk of MACCE (P = 0.024). In patients with
      AF undergoing coronary artery stenting, MACCE were reduced by warfarin therapy
      without increased bleeding, which might be related to tighter control with a
      lower INR value.

PMID- 23974945
TI  - Developing a conceptual framework of urban health observatories toward
      integrating research and evidence into urban policy for health and health equity.
AB  - Detailed information on health linked to geographic, sociodemographic, and
      environmental data are required by city governments to monitor health and the
      determinants of health. These data are critical for guiding local interventions,
      resource allocation, and planning decisions, yet they are too often non-existent
      or scattered. This study aimed to develop a conceptual framework of Urban Health
      Observatories (UHOs) as an institutional mechanism which can help synthesize
      evidence and incorporate it into urban policy-making for health and health
      equity. A survey of a select group of existent UHOs was conducted using an
      instrument based on an a priori conceptual framework of key structural and
      functional characteristics of UHOs. A purposive sample of seven UHOs was
      surveyed, including four governmental, two non-governmental, and one university
      based observatory, each from a different country. Descriptive and framework
      analysis methods were used to analyze the data and to refine the conceptual
      framework in light of the empirical data. The UHOs were often a product of unique
      historical circumstances. They were relatively autonomous and capable of
      developing their own locally sensitive agenda. They often had strong networks for
      accessing data and were able to synthesize them at the urban level as well as
      disaggregate them into smaller units. Some UHOs were identified as not only
      assessing but also responding to local needs. The findings from this study were
      integrated into a conceptual framework which illustrates how UHOs can play a
      vital role in monitoring trends in health determinants, outcomes, and equity;
      optimizing an intersectoral urban information system; incorporating research on
      health into urban policies and systems; and providing technical guidance on
      research and evidence-based policy making. In order to be most effective, UHOs
      should be an integral part of the urban governance system, where multiple sectors
      of government, the civil society, and businesses can participate in taking the
      right actions to promote health equity. 

PMID- 23974946
TI  - Substance use and HIV risk behavior among men who have sex with men: the role of
      sexual compulsivity.
AB  - The relationship between substance use, sexual compulsivity and sexual risk
      behavior was assessed with a probability-based sample of men who have sex with
      men (MSM). Stimulant, poppers, erectile dysfunction medication (EDM), alcohol
      use, and sexual compulsivity were independently associated with higher odds of
      engaging in any serodiscordant unprotected anal intercourse (SDUAI). The
      association of sexual compulsivity with SDUAI was moderated by poppers and EDM
      use. Behavioral interventions are needed to optimize biomedical prevention of HIV
      among substance using MSM. 

PMID- 23974947
TI  - Tension-related activity in the orbitofrontal cortex and amygdala: an fMRI study
      with music.
AB  - Tonal music is characterized by a continuous flow of tension and resolution. This
      flow of tension and resolution is closely related to processes of expectancy and
      prediction and is a key mediator of music-evoked emotions. However, the neural
      correlates of subjectively experienced tension and resolution have not yet been
      investigated. We acquired continuous ratings of musical tension for four piano
      pieces. In a subsequent functional magnetic resonance imaging experiment, we
      identified blood oxygen level-dependent signal increases related to musical
      tension in the left lateral orbitofrontal cortex (pars orbitalis of the inferior
      frontal gyrus). In addition, a region of interest analysis in bilateral amygdala
      showed activation in the right superficial amygdala during periods of increasing
      tension (compared with decreasing tension). This is the first neuroimaging study
      investigating the time-varying changes of the emotional experience of musical
      tension, revealing brain activity in key areas of affective processing. 

PMID- 23974948
TI  - Cumulative risk on the oxytocin receptor gene (OXTR) underpins empathic
      communication difficulties at the first stages of romantic love.
AB  - Empathic communication between couples plays an important role in relationship
      quality and individual well-being and research has pointed to the role of
      oxytocin in providing the neurobiological substrate for pair-bonding and empathy.
      Here, we examined links between genetic variability on the oxytocin receptor gene
      (OXTR) and empathic behaviour at the initiation of romantic love. Allelic
      variations on five OXTR single nucleotide polymorphisms (SNPs) previously
      associated with susceptibility to disorders of social functioning were genotyped
      in 120 new lovers: OXTRrs13316193, rs2254298, rs1042778, rs2268494 and rs2268490.
      Cumulative genetic risk was computed by summing risk alleles on each SNP. Couples
      were observed in support-giving interaction and behaviour was coded for empathic
      communication, including affective congruence, maintaining focus on partner,
      acknowledging partner's distress, reciprocal exchange and non-verbal empathy.
      Hierarchical linear modelling indicated that individuals with high OXTR risk
      exhibited difficulties in empathic communication. OXTR risk predicted empathic
      difficulties above and beyond the couple level, relationship duration, and
      anxiety and depressive symptoms. Findings underscore the involvement of oxytocin
      in empathic behaviour during the early stages of social affiliation, and suggest
      the utility of cumulative risk and plasticity indices on the OXTR as potential
      biomarkers for research on disorders of social dysfunction and the neurobiology
      of empathy.

PMID- 23974949
TI  - Dissociation of a trait and a valence representation in the mPFC.
AB  - A previous functional MRI adaptation study on trait inference indicated that a
      trait code is located in the ventral medial prefrontal cortex (vmPFC), but could
      not rule out that this adaptation effect is due to the trait's underlying
      valence. To address this issue, we presented sentences describing positive and
      negative valences of either a human trait or object characteristic, and
      manipulated whether the human trait or object characteristic was repeated or not,
      either with the same or opposite valance. In two trait conditions, a behavioral
      trait-implying sentence was preceded by a prime sentence that implied the same or
      the opposite trait. The results confirmed the earlier finding of robust trait
      adaptation from prime to target in the vmPFC, and also found adaptation in the
      precuneus and right mid-occipital cortex. In contrast, no valence adaptation was
      found in two novel object conditions, in which the target sentence again implied
      a positive or negative trait, but was preceded by a prime sentence that described
      an object with the same or the opposite valence. Together with the previous
      study, this indicates that a specific trait code, but not a generalized valence
      code, is represented in the vmPFC. 

PMID- 23974950
TI  - MiR-146a regulates IL-6 production in lipopolysaccharide-induced RAW264.7
      macrophage cells by inhibiting Notch1.
AB  - Inflammatory cells, macrophages induced by lipopolysaccharide (LPS) stimulation,
      lead to the production of inflammatory cytokines, which are crucial to host
      defense. MicroRNAs are short noncoding RNAs that regulate key biological
      processes via suppression of gene expression at posttranscriptional levels.
      Recently, miR-146a has been shown to be involved in the regulation of immune and
      inflammatory responses. However, the role of miR-146a in LPS-induced RAW264.7
      macrophage cells remains unclear. In this study, we found that the expression of
      miR-146a was upregulated in RAW264.7 macrophage cells in response to LPS
      stimulation in a dose- and time-dependent manner by one-step real-time
      quantitative PCR. In addition, miR-146a mimics decreased, while miR-146a
      inhibitor increased, the expression of inflammatory cytokine interleukin-6, but
      did not affect tumor necrosis factor-alpha expression in LPS-stimulated RAW264.7
      macrophage cells. Bioinformatics analyses predict that Notch1 is a potential
      target of miR-146a. Moreover, miR-146a overexpression in LPS-treated RAW264.7
      macrophage cells did significantly decrease Notch1 mRNA and protein levels. These
      results suggested that miR-146a may function as a novel feedback negative
      regulator to LPS-induced production of inflammatory cytokines, at least in part,
      via inhibiting the expression of Notch1.

PMID- 23974951
TI  - Retinal detachment and proliferative vitreoretinopathy: central retinal artery
      blood velocities, intraocular pressure, and endothelin 1.
AB  - PURPOSE: To analyze if endothelin 1 may have an effect on central retinal artery
      (CRA) blood flow velocities and intraocular pressure (IOP) in retinal detachment.
      METHODS: Using radioimmunoassay, immunoreactive endothelin 1 levels were tested
      in both plasma and subretinal fluid specimens from patients with retinal
      detachment, while only plasma specimens from healthy subjects were tested.
      Central retinal artery Doppler sonography parameters and IOP were measured in
      eyes with retinal detachment, with and without proliferative vitreoretinopathy,
      their respective healthy fellow eyes, and normal eyes. RESULTS: Retinal
      detachment eyes had lower CRA peak systolic velocity and end-diastolic velocity,
      lower IOP, and higher plasma immunoreactive endothelin 1 levels than normal eyes
      (P < 0.0001). Eyes with proliferative vitreoretinopathy had lower CRA peak
      systolic velocity and end-diastolic velocity, higher resistivity index, lower
      IOP, higher plasma immunoreactive endothelin 1 levels, and higher subretinal
      fluid immunoreactive endothelin 1 than eyes without proliferative
      vitreoretinopathy (P < 0.0001). A statistically significant linear correlation
      was found among CRA parameters, IOP, and subretinal fluid immunoreactive
      endothelin 1 measurements. CONCLUSION: Endothelin 1 has shown a close
      relationship with IOP and CRA blood flow changes associated to retinal detachment
      as well as with proliferative vitreoretinopathy complications.

PMID- 23974952
TI  - The relationship between inner retinal cavitation, photoreceptor disruption, and
      the integrity of the outer limiting membrane in macular telangiectasia type 2.
AB  - PURPOSE: The authors analyzed the relationship between the integrity of the outer
      limiting membrane (OLM) and the presence of inner retinal cavitation and
      photoreceptor disruption in eyes with macular telangiectasia Type 2 (MacTel Type
      2). METHODS: Cirrus optical coherence tomography images were analyzed with
      attention to the presence or absence of inner and outer retinal cavities,
      photoreceptor loss, or disruption and OLM integrity. RESULTS: Ninety-seven eyes
      with MacTel Type 2 that were suitable for analysis were identified. The OLM was
      intact in all 48 eyes with inner retinal cavities without photoreceptor
      disruption. By contrast, the OLM was absent or disrupted in 8 of 10 eyes with
      photoreceptor disruption. CONCLUSION: If Muller cell disruption contributes to
      inner retinal cavitation, it does not appear to affect the OLM, which is the only
      part of the Muller cell that is visible clinically. By contrast, the integrity of
      both the OLM and photoreceptors appear to be closely linked in MacTel Type 2.
      This observation is consistent with the hypothesis that Muller cell dysfunction
      plays a role in the pathogenesis of MacTel.

PMID- 23974953
TI  - Peripheral retinal nonperfusion in fellow eyes in coats disease.
AB  - PURPOSE: To measure peripheral nonperfusion and describe bilateral vascular
      abnormalities in patients with Coats disease, emphasizing subtle findings in the
      contralateral eyes of patients diagnosed with unilateral disease. METHODS:
      Clinical records, including retina drawings and fluorescein angiography images
      obtained under anesthesia, were retrospectively reviewed from consecutive
      pediatric patients with Coats disease. The main outcome measure was disk
      diameters of peripheral nonperfusion and proportion of Coats disease patients
      with bilateral findings. RESULTS: Twenty-two of 32 patients with Coats disease
      had bilateral abnormal peripheral vasculature. In Group 1 (classic Coats disease:
      presumed unilateral, ocular only disease), 15 of 24 patients had peripheral
      nonperfusion >2 disk diameters in their contralateral eyes, 5 with telangiectasis
      and/or microaneurysms. Seven of 8 patients in Group 2 (Coats-like disease:
      systemic and/or clinically bilateral disease) had bilateral vascular anomalies.
      CONCLUSION: Bilateral vascular abnormalities are more common in Coats disease
      than previously reported. This observation supports a systemic and/or genetic
      association with Coats disease. Patients with Coats disease should have careful
      evaluation of the periphery of the less affected eye, preferably with fluorescein
      angiography, to identify vascular changes not visible clinically. Both eyes
      warrant surveillance over the lifetime of the patient for potential progression
      to exudative disease that would warrant treatment.

PMID- 23974954
TI  - Clinical disease activity, C-reactive protein normalisation and mucosal healing
      in Crohn's disease in the SONIC trial.
AB  - BACKGROUND AND AIMS: The Crohn's Disease Activity Index (CDAI) has been
      criticised due to heavy weighting on subjective clinical symptoms. C-reactive
      protein (CRP) and endoscopic lesions are objective measures of inflammation. We
      investigated the relationships between clinical disease activity, CRP
      normalisation and mucosal healing in Crohn's disease (CD). METHODS: The Study of
      Biologic and Immunomodulator Naive Patients in CD trial compared infliximab to
      azathioprine and to infliximab plus azathioprine in 508 CD patients. Mucosal
      healing was defined as the absence of mucosal ulceration at the week 26
      ileocolonoscopy in a patient who had evidence of ulceration at the baseline
      ileocolonoscopy. RESULTS: 188 patients who had evaluable ileocolonoscopy with
      evidence of mucosal ulceration at baseline, CDAI scores and CRP values at
      baseline and week 26 were analysed. Seventy-two of 136 patients (53%) who had a
      CDAI<150 at week 26 achieved mucosal healing, and 38 of 90 patients (42%)
      achieved both CRP normalisation (CRP<0.8 mg/dL) and mucosal healing while in
      clinical remission. The positive predictive value (PPV) and negative predictive
      value (NPV) of CDAI to detect mucosal healing using 150 as a cut-off for CDAI
      were 65% and 53%, respectively. The PPV and NPV of CDAI to detect mucosal healing
      and CRP normalisation using 150 as a cut-off for CDAI were 79% and 42%,
      respectively. CONCLUSIONS: Half the patients under azathioprine and/or infliximab
      in clinical remission have endoscopic and/or CRP evidence of residual active CD,
      whereas other patients with endoscopic and CRP normalisation have persistent
      clinical symptoms. Clinical symptoms as scored by CDAI are not a reliable measure
      of the underlying inflammation.

PMID- 23974955
TI  - Does injury prevention education initiate household changes in a Spanish-speaking
      minority population?
AB  - Young children from low income families are among the most affected population of
      unintentional injury. This non-randomized longitudinal study examined knowledge
      for home and child safety with an injury prevention training offered to parents
      of children who reside in the Rio Grande Valley of Texas. Eighty eight parents
      received the training and pre-and post-test surveys were used to measure
      knowledge outcomes. A follow-up survey was conducted 2 months after the
      educational intervention to identify how many parents reported household and
      safety behavior changes as a result of the training. The most significant change
      in behavior, as it pertains to the household, was related to locking and storage
      of dangerous cleaning chemicals. Other significant changes in behavior were in
      areas that directly related to the child such as learning how to swim, use of sun
      block and fire safety in the home. This study suggests that tailored trainings
      can improve parent knowledge and change in behaviors for the promotion of safety
      activities to avoid risks for unintentional injuries. Further, the study
      identified certain at-risk areas that need to be addressed from an educational
      perspective. These areas include bicycle and water safety; specifically, the use
      of protective gear when bicycling; understanding and adhering to traffic rules
      when bicycling; and, the dangers of drowning in small quantities of water. 

PMID- 23974956
TI  - MEF2B mutations lead to deregulated expression of the oncogene BCL6 in diffuse
      large B cell lymphoma.
AB  - MEF2B encodes a transcriptional activator and is mutated in ~11% of diffuse large
      B cell lymphomas (DLBCLs) and ~12% of follicular lymphomas (FLs). Here we found
      that MEF2B directly activated the transcription of the proto-oncogene BCL6 in
      normal germinal-center (GC) B cells and was required for DLBCL proliferation.
      Mutation of MEF2B resulted in enhanced transcriptional activity of MEF2B either
      through disruption of its interaction with the corepressor CABIN1 or by rendering
      it insensitive to inhibitory signaling events mediated by phosphorylation and
      sumoylation. Consequently, the transcriptional activity of Bcl-6 was deregulated
      in DLBCLs with MEF2B mutations. Thus, somatic mutations of MEF2B may contribute
      to lymphomagenesis by deregulating BCL6 expression, and MEF2B may represent an
      alternative target for blocking Bcl-6 activity in DLBCLs. 

PMID- 23974957
TI  - GATA-3 regulates the self-renewal of long-term hematopoietic stem cells.
AB  - The transcription factor GATA-3 is expressed and required for differentiation and
      function throughout the T lymphocyte lineage. Despite evidence it may also be
      expressed in multipotent hematopoietic stem cells (HSCs), any role for GATA-3 in
      these cells has remained unclear. Here we found GATA-3 was in the cytoplasm in
      quiescent long-term stem cells from steady-state bone marrow but relocated to the
      nucleus when HSCs cycled. Relocation depended on signaling via the mitogen
      activated protein kinase p38 and was associated with a diminished capacity for
      long-term reconstitution after transfer into irradiated mice. Deletion of Gata3
      enhanced the repopulating capacity and augmented the self-renewal of long-term
      HSCs in cell-autonomous fashion without affecting the cell cycle. Our
      observations position GATA-3 as a regulator of the balance between self-renewal
      and differentiation in HSCs that acts downstream of the p38 signaling pathway. 

PMID- 23974958
TI  - Use of a fundamental approach to spray-drying formulation design to facilitate
      the development of multi-component dry powder aerosols for respiratory drug
      delivery.
AB  - PURPOSE: A fundamental approach incorporating current theoretical models into
      aerosol formulation design potentially reduces experimental work for complex
      formulations. A D-amino acid mixture containing D-Leucine (D-Leu), D-Methionine,
      D-Tryptophan, and D-Tyrosine was selected as a model formulation for this
      approach. METHODS: Formulation design targets were set, with the aim of producing
      a highly dispersible D-amino acid aerosol. Particle formation theory and a spray
      dryer process model were applied with boundary conditions to the design targets,
      resulting in a priori predictions of particle morphology and necessary spray
      dryer process parameters. Two formulations containing 60% w/w trehalose, 30% w/w
      D-Leu, and 10% w/w remaining D-amino acids were manufactured. RESULTS: The design
      targets were met. The formulations had rugose and hollow particles, caused by
      deformation of a crystalline D-Leu shell while trehalose remained amorphous, as
      predicted by particle formation theory. D-Leu acts as a dispersibility enhancer,
      ensuring that both formulations: 1) delivered over 40% of the loaded dose into
      the in vitro lung region, and 2) achieved desired values of lung airway surface
      liquid concentrations based on lung deposition simulations. CONCLUSIONS:
      Theoretical models were applied to successfully achieve complex formulations with
      design challenges a priori. No further iterations to the design process were
      required.

PMID- 23974959
TI  - Intraoperative liver ultrasound still affects surgical strategy for patients with
      colorectal metastases in the modern era.
AB  - BACKGROUND: The present study was designed to evaluate the role of intraoperative
      ultrasound (IOUS) in intrahepatic staging and the impact on surgical strategy for
      patients with colorectal liver metastases (CRLM). METHODS: The study included 515
      patients who had undergone liver resection for CRLM at two tertiary care referral
      centers. Data from a prospectively collected database were retrospectively
      analysed. Early intrahepatic recurrence was assessed at 3 and 6 months after
      resection and was considered as residual disease undetected by IOUS. Performance
      of imaging modalities was compared by analysis of studies on individual patients.
      RESULTS: A total of 1,370 liver metastases were detected preoperatively with a
      median of 3 imaging modalities. MRI and PET were performed in 51 and 42 % of the
      patients, respectively. Median number of days between last imaging and surgery
      was 18. Contrast-enhanced IOUS was performed in 136 patients (26.4 %).
      Intraoperatively, 293 new nodules were found in 132 patients: on histology 280
      were CRLM (17.6 %). Surgical strategy was changed in 140 patients (27.2 %). On
      multivariate analysis synchronous and bilobar metastases >= 3 in number, BMI >=
      30, and time between last imaging and surgery longer than 18 days resulted in
      predictive factors indicating new nodules detected by IOUS. Early intrahepatic
      recurrences were 3.7 and 7.9 % at 3 and 6 months. Performance of CT, MRI, FDG
      PET, and intraoperative staging was compared: sensitivity was 63.6, 68.8, 53.6,
      and 92 % and specificity was 91, 92.3, 95.8, and 97.8 %, respectively
      CONCLUSIONS: The use of IOUS continues to be mandatory for correct staging of
      patients with CRLM undergoing liver resection.

PMID- 23974961
TI  - Serum albumin and prothrombin time before entecavir treatment in chronic
      hepatitis B or cirrhosis are related to amelioration of liver function after
      treatment.
AB  - OBJECTIVES: Nucleotide analogs such as entecavir (ETV) ameliorate liver function
      in chronic hepatitis B or cirrhotic patients, but we cannot predict in which
      patients this will occur before ETV treatment. We aimed to develop a new
      pretherapeutic predictive model for the amelioration of liver function after
      treatment. PATIENTS AND METHODS: We carried out a case-control study involving 88
      chronic hepatitis B or cirrhotic patients who underwent ETV treatment at Kobe
      University Hospital. Blood biochemical and virological examinations were
      performed before and 1 year after ETV treatment. Child's score as an indicator of
      liver function was also evaluated at the same time. Factors associated with
      amelioration of Child's score 1 year after ETV treatment were assessed by
      multivariate analyses. A predictive model of Child's score amelioration was
      established. RESULTS: Multivariate analyses showed that albumin (Alb) and
      prothrombin time (PT) before ETV treatment were independent factors for Child's
      score amelioration after the treatment (P=0.001 and 0.030, respectively). The
      decreases in Alb and PT before the treatment were significantly related to the
      decrease in Child's score 1 year after the treatment (P=0.001 and 0.006,
      respectively). The following predictive model of Child's score amelioration was
      developed: P=1-(1/(1+Exp(-2.215*Alb-0.058*PT+12.543))). The model could well
      discriminate area under ROC at 0.819 (95% confidence interval: 0.707-0.932). The
      optimal cutoff point was 0.185, and sensitivity and specificity were 83.3 and
      73.9%, respectively. CONCLUSION: Alb and PT before ETV treatment were related to
      amelioration of liver function after treatment. With our model, the probability
      of amelioration of liver function after treatment could be better estimated.

PMID- 23974962
TI  - The influence of waiting times on cost-effectiveness: a case study of colorectal
      cancer mass screening.
AB  - When a cost-effectiveness analysis is implemented, the health-care system is
      usually assumed to adjust smoothly to the proposed new strategy. However,
      technological innovations in health care may often induce friction in the
      organization of care supply, implying the congestion of services and subsequent
      waiting times. Our objective here is to measure how these short run rigidities
      can challenge cost-effectiveness recommendations favorable to an innovative mass
      screening test for colorectal cancer. Using Markov modeling, we compare the
      standard Guaiac fecal occult blood test (gFOBT) with an innovative screening test
      for colorectal cancer, namely the immunological fecal occult blood test (iFOBT).
      Waiting time can occur between a positive screening test and the subsequent
      confirmation colonoscopy. Five scenarios are considered for iFOBT: no further
      waiting time compared with gFOBT, twice as much waiting time for a period of 5 or
      10 years, and twice as much waiting time for a period of 5 or 10 years combined
      with a 25% decrease in participation to confirmation colonoscopies. According to
      our modeling, compared with gFOBT, iFOBT would approximately double colonoscopy
      demand. Probabilistic sensitivity analysis enables concluding that the waiting
      time significantly increases the uncertainty surrounding recommendations
      favorable to iFOBT if it induces a decrease in the adherence rate for
      confirmation colonoscopy.

PMID- 23974963
TI  - Methodological reviews of economic evaluations in health care: what do they
      target?
AB  - INTRODUCTION AND OBJECTIVES: An increasing number of published studies of
      economic evaluations of health technologies have been reviewed and summarized
      with different purposes, among them to facilitate decision-making processes.
      These reviews have covered different aspects of economic evaluations, using a
      variety of methodological approaches. The aim of this study is to analyze the
      methodological characteristics of the reviews of economic evaluations in health
      care, published during the period 1990-2010, to identify their main features and
      the potential missing elements. This may help to develop a common procedure for
      elaborating these kinds of reviews. METHODS: We performed systematic searches in
      electronic databases (Scopus, Medline and PubMed) of methodological reviews
      published in English, period 1990-2010. We selected the articles whose main
      purpose was to review and assess the methodology applied in the economic
      evaluation studies. We classified the data according to the study objectives,
      period of the review, number of reviewed studies, methodological and non
      methodological items assessed, medical specialty, type of disease and technology,
      databases used for the review and their main conclusions. We performed a
      descriptive statistical analysis and checked how generalizability issues were
      considered in the reviews. RESULTS: We identified 76 methodological reviews, 42
      published in the period 1990-2001 and 34 during 2002-2010. The items assessed
      most frequently (by 70% of the reviews) were perspective, type of economic study,
      uncertainty and discounting. The reviews also described the type of intervention
      and disease, funding sources, country in which the evaluation took place, type of
      journal and author's characteristics. Regarding the intertemporal comparison,
      higher frequencies were found in the second period for two key methodological
      items: the source of effectiveness data and the models used in the studies.
      However, the generalizability issues that apparently are creating a growing
      interest in the economic evaluation literature did not receive as much attention
      in the reviews of the second period. The remaining items showed similar
      frequencies in both periods. CONCLUSIONS: Increasingly more reviews of economic
      evaluation studies aim to analyze the application of methodological principles,
      and offer summaries of papers classified by either diseases or health
      technologies. These reviews are useful for finding literature trends, aims of
      studies and possible deficiencies in the implementation of methods of specific
      health interventions. As no significant methodological improvement was clearly
      detected in the two periods analyzed, it would be convenient to pay more
      attention to the methodological aspects of the reviews.

PMID- 23974964
TI  - Estimating the social cost of respiratory cancer cases attributable to
      occupational exposures in France.
AB  - PURPOSE: The objective of this article was to estimate the social cost of
      respiratory cancer cases attributable to occupational risk factors in France in
      2010. METHODS: According to the attributable fraction method and based on
      available epidemiological data from the literature, we estimated the number of
      respiratory cancer cases due to each identified risk factor. We used the cost-of
      illness method with a prevalence-based approach. We took into account the direct
      and indirect costs. We estimated the cost of production losses due to morbidity
      (absenteeism and presenteeism) and mortality costs (years of production losses)
      in the market and nonmarket spheres. RESULTS: The social cost of lung, larynx,
      sinonasal and mesothelioma cancer caused by exposure to asbestos, chromium,
      diesel engine exhaust, paint, crystalline silica, wood and leather dust in France
      in 2010 were estimated at between 917 and 2,181 million euros. Between 795 and
      2,011 million euros (87-92%) of total costs were due to lung cancer alone.
      Asbestos was by far the risk factor representing the greatest cost to French
      society in 2010 at between 531 and 1,538 million euros (58-71%), ahead of diesel
      engine exhaust, representing an estimated social cost of between 233 and 336
      million euros, and crystalline silica (119-229 million euros). Indirect costs
      represented about 66% of total costs. CONCLUSION: Our assessment shows the
      magnitude of the economic impact of occupational respiratory cancers. It allows
      comparisons between countries and provides valuable information for policy-makers
      responsible for defining public health priorities.

PMID- 23974965
TI  - A new murine osteoblastic cell line immortalized with the SV40 large T antigen.
AB  - The murine preosteoblastic cell line, MC3T3-E1, is widely used to study bone
      formation and differentiation in vitro. However, this cell line is unstable in
      culture. The current study was designed to establish a stable osteoblastic cell
      line. A mammalian expression vector carrying the SV 40 large T antigen was
      introduced into a primary culture of cells isolated from the calvaria of newborn
      mice. Among isolated cell lines, the MN16 cell line was selected for further
      characterization. The MN16 cell line was cultured for 28 days, and compared with
      the MC3T3-E1 cell line with or without induction. The expression of bone-related
      genes was examined using the real-time RT-PCR technique. Alizarin red and von
      Kossa staining were used to detect mineralization of nodules in the cultures. The
      cell line showed the characteristics of osteoblastic cells in term of gene
      expression patterns of various molecular markers and calcium deposition in the
      cell layer after induction. Furthermore, the MN16 cells showed strong adhesion to
      the basic domain of collagen, a result that is specific for bone-derived cells.
      The MN16 cell line was found to be stably differentiated into bone formation
      cells in vitro and should be useful for studying bone biology.

PMID- 23974967
TI  - Rhabdoid meningioma: analysis of one case.
AB  - INTRODUCTION: Rhabdoid meningioma (RM) is rare, and it occurs mainly in children.
      We report the clinical and pathological features of rhabdoid meningioma in a 9
      year-old child. MATERIAL AND METHODS: A 9-year-old child with RM presented to our
      hospital with headache that had persisted for 3 days. Magnetic resonance imaging
      of his brain demonstrated supratentorial lesions of the right temporal petrous
      bone and cisterna magna cyst. He underwent surgery on January 13, 2010. The
      pathological diagnosis was rhabdoid meningioma (grade III). The patient underwent
      radiotherapy with 30 Gy/16 fractions delivered to the recurrent tumor after
      surgery. The patient died in December as a result of complications of recurrent
      meningioma. CONCLUSION: The accumulated data, including this current case,
      demonstrate the difficulties in reaching the diagnosis and providing treatment
      for this disease as a consequence of its low incidence, aggressive nature, and
      poor treatment options for children with rhabdoid meningioma.

PMID- 23974966
TI  - Ambient hypoxia enhances the loss of muscle mass after extensive injury.
AB  - Hypoxia induces a loss of skeletal muscle mass and alters myogenesis in vitro,
      but whether it affects muscle regeneration in vivo following injury remains to be
      elucidated. We hypothesized that hypoxia would impair the recovery of muscle mass
      during regeneration. To test this hypothesis, the soleus muscle of female rats
      was injured by notexin and allowed to recover for 3, 7, 14, and 28 days under
      normoxia or hypobaric hypoxia (5,500 m) conditions. Hypoxia impaired the
      formation and growth of new myofibers and enhanced the loss of muscle mass during
      the first 7 days of regeneration, but did not affect the final recovery of muscle
      mass at 28 days. The impaired regeneration under hypoxic conditions was
      associated with a blunted activation of mechanical target of rapamycin (mTOR)
      signaling as assessed by p70(S6K) and 4E-BP1 phosphorylation that was independent
      of Akt activation. The decrease in mTOR activity with hypoxia was consistent with
      the increase in AMP-activated protein kinase activity, but not related to the
      change in regulated in development and DNA response 1 protein content. Hypoxia
      increased the mRNA levels of the atrogene muscle ring finger-1 after 7 days of
      regeneration, though muscle atrophy F box transcript levels remained unchanged.
      The increase in MyoD and myogenin mRNA expression with regeneration was
      attenuated at 7 days with hypoxia. In conclusion, our results support the notion
      that the enhanced loss of muscle mass observed after 1 week of regeneration under
      hypoxic conditions could mainly result from the impaired formation and growth of
      new fibers resulting from a reduction in protein synthesis and satellite cell
      activity. 

PMID- 23974968
TI  - Clinical manifestation and neurosurgical intervention of encephalocraniocutaneous
      lipomatosis--a case report and review of the literature.
AB  - INTRODUCTION: Currently, there are only a few reported cases of symptomatic or
      asymptomatic subpial (intramedullary) spinal lipoma, and therefore no guidelines
      are available to indicate surgery. These lesions are infrequently associated with
      spina bifida. CASE REPORT: Herein, we provide our experience in the neurosurgical
      intervention of compressive myeloradiculopathy for encephalocraniocutaneous
      lipomatosis (ECCL). The patient initially presented with bilateral upper hand
      paralysis, then regained muscle power after surgery and during 1 year of follow
      up. We discuss the neurosurgical indications and intervention, imaging studies,
      other associated symptoms, and the pathogenesis of ECCL in an infant.

PMID- 23974969
TI  - Craniocerebral disproportion: a topical review and proposal toward a new
      definition, diagnosis, and treatment protocol.
AB  - INTRODUCTION: At some point in their lives, patients previously shunted for
      hydrocephalus may experience chronic, debilitating headaches, despite the fact
      that their shunts are functioning properly. Previously published reports have
      suggested that a subset of these patients may be suffering from an iatrogenic
      craniocerebral disproportion (CCD) and, therefore, may benefit from procedures
      that expand the available intracranial space. A unified definition of this
      disorder, however, is lacking. DISCUSSION: Here, the authors chart the history
      (including historical terminology) of CCD, review its incidence, describe its
      signs, symptoms, and associated radiologic findings, and expound upon its
      pathophysiology. Next, a concise clinical definition of CCD based on the temporal
      correlation of headaches with the appearance of plateau waves on intracranial
      pressure (ICP) monitoring is proposed. The authors conclude with a discussion of
      the various therapeutic strategies employed previously to treat this disorder and
      present their individualized treatment strategy based upon the simultaneous
      utilization of ICP monitors and gradual external cranial vault expansion.

PMID- 23974970
TI  - Comparison between laser- and diathermy-assisted posterior cordotomy for
      bilateral vocal cord abductor paralysis.
AB  - IMPORTANCE: A reliable procedure is needed to solve the problem of difficult
      airway in patients with bilateral vocal cord paralysis without adversely
      affecting patient "voice quality." OBJECTIVES: To compare the results of laser
      assisted posterior cordotomy with diathermy-assisted posterior cordotomy for
      bilateral vocal cord paralysis in regard to dyspnea severity, voice quality, and
      aspiration. DESIGN: Prospective randomized clinical trial at a university medical
      center. SETTING: Zagazig University Hospitals, Zagazig, Egypt. PARTICIPANTS:
      Twenty patients randomly categorized into 2 groups; group A was treated with
      laser-assisted posterior cordotomy and group B was treated with diathermy
      assisted posterior cordotomy. INTERVENTION: Laser-assisted posterior cordotomy
      for group A and diathermy-assisted posterior cordotomy for group B. MAIN OUTCOME
      AND MEASURE: Dyspnea severity, voice quality, and aspiration. RESULTS: A
      significant difference (P < .05) was found between group A and group B at all
      postoperative comparisons in dyspnea, whereas no significant difference (P >=
      .05) was detected at all postoperative comparisons in voice quality. CONCLUSIONS
      AND RELEVANCE: Laser-assisted posterior cordotomy can be considered as a reliable
      and superior procedure compared with diathermy-assisted posterior cordotomy in
      the treatment of bilateral vocal cord abductor paralysis. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: ISRCTN08093874.

PMID- 23974972
TI  - [The significance of early diagnosis of cancer-related hypercalcaemia].
AB  - Cancer-related hypercalcaemia is one of the most common life-threatening
      metabolic disorders. It occurs in 20% to 30% of patients with cancer during the
      course of the disease, which depends on tumour type, too. There are two types of
      cancer-related hypercalcemia: humoral hypercalcemia and local osteolytic
      hypercalcaemia. Malignant hypercalcaemia is mediated by several circulating
      factors secreted by malignant cells. The biological actions of these factors are
      primarily stimulation of osteoclasts to resorb bone and, secondly, stimulation of
      calcium reabsorption at the renal tubules resulting in an elevation of serum
      calcium level. Diagnosis of hypercalcaemia is relatively difficult due to the non
      specific clinical signs as well as the underlying malignancy and the side-effects
      of palliative medical treatment. Consequently, cancer-related hypercalcaemia is
      underdiagnosed quite often. Unrecognised malignant hypercalcaemia can lead to
      death. Nowadays 90% of hypercalcaemia can be treated with administration of
      intravenous saline containing fluids and bisphosphonates. Literature data suggest
      that hypercalcaemia is treated in less than 40% of hospitalized patients properly
      due to diagnostic errors and mismanagement.

PMID- 23974971
TI  - Real-time dynamics of methyl-CpG-binding domain protein 3 and its role in DNA
      demethylation by fluorescence correlation spectroscopy.
AB  - With unprecedented development in technology, epigenetics is recognized as a
      substantial and flexible regulatory pathway for phenotyping. Cytosine methylation
      and its subsequent oxidization have attracted significant attention due to their
      direct impact on gene regulation, in association with methyl-CpG-binding domain
      proteins (MBDs) and transcription related factors. In this study we record the
      dynamics of DNA demethylation using the recombinant MBD3-GFP protein in living
      cells under hypoxia and Decitabine treatment using Fluorescence Correlation
      Spectroscopy (FCS) by monitoring the diffusion dynamics of MBD3. Our study shows
      a DNA-replication-independent decrease of 5-methylcytosine (5mC)/5
      hydroxymethylcytosine (5hmC) under hypoxia vs. a dependent decrease under
      Decitabine treatment. Further, we define a significantly faster diffusion of MBD3
      in the nucleus as a precursory event for active demethylation rather than the
      Decitabine induced passive demethylation. By monitoring the diffusion of bound
      and unbound MBD3 in the nucleus we were able to identify and characterize hypoxia
      sensitive cells from insensitive/tolerant cells, as well as the respective
      contribution to active demethylation in a time-dependent manner. Last, we
      quantitatively describe the concurrent decreasing trend in all of the three
      oxidized products of 5mC, which points to the potential involvement of ten-eleven
      translocation proteins (TETs) in hypoxia induced active demethylation. Overall,
      for the first time we correlate the dynamic process of DNA demethylation with the
      biophysical properties of the corresponding DNA binding proteins in live single
      cells by single molecule spectroscopy. 

PMID- 23974973
TI  - [Useful tests to assess the clinical usefulness of new prognostic markers: the
      example of heart failure].
AB  - INTRODUCTION: Identification of risk factors is one of the most frequent
      questions in medical research currently. Several reports showed "significant" and
      "independent" prognostic factors in a variety of human conditions, however, those
      were not tested about predictive information in addition to standard risk
      markers. Recently novel statistical approaches (reclassification) have been
      developed to test the performance and usefulness of new risk factors and
      prognostic markers. There are several established methods to test the prognostic
      models. AIM: The aim of this work was to present the application of these novel
      statistical approaches by re-analyzing previously reported results of the
      authors. METHOD: The authors analyzed the prognostic role of two markers: red
      cell distribution width and heat shock protein 70 in patients with heart failure.
      Using Cox regression analyses the authors have reported previously that both
      markers are independent predictors. In the present study they re-analyzed the
      role of red cell distribution width and heat shock protein 70 by reclassification
      tests. RESULTS: Incorporating red cell distribution width to the reference model
      the authors found a significant improvement in discrimination . However, the
      reclassification analysis provided ambiguous results with heat shock protein 70.
      CONCLUSIONS: Interpretation of results on new prognostic factors has to be done
      carefully, and appropriate reclassification approaches may help to confirm
      clinical usefulness only.

PMID- 23974974
TI  - [Survey of quality of life of rheumatoid arthritis patients admitted to
      rehabilitation centres in Hungary].
AB  - INTRODUCTION: There are limited data about the quality of life of rheumatoid
      arthritis patients admitted to rehabilitation centres in Hungary. AIM: The aim of
      the authors was to assess demographic data, social status, health related quality
      of life, and needs for assistance and disease-related information of 239
      rheumatoid arthritis patients (169 women and 7 men) admitted to four
      rehabilitation centres in Hungary. METHOD: For the assessment of demographic,
      social and other data the authors developed questionnaires. The health related
      quality of life was evaluated using the validated Short Form 36 questionnaire.
      RESULTS: The authors found that rheumatoid arthritis patients require in-patient
      rehabilitation relatively early in their disease course. 80.4% of the patients
      were over 50 years of age, and their social status was low as compared to the
      average of the Hungarian population. The health related quality of life of
      patients was significantly lower than that of the average population, but it was
      similar to the quality of life of patients with osteoarthritis, osteoporosis and
      low back pain. Among domains of the quality of life, the scores for physical
      function and pain were the lowest. The most common accompanying diseases included
      hypertension and osteoporosis. In case of knee and hip surgeries, postoperative
      rehabilitation was performed in due time. Patients were not satisfied with
      disease-related information and education given by health care providers.
      CONCLUSIONS: There is poor quality of life of rheumatoid arthritis patients
      admitted to rehabilitation centres in Hungary. More efforts should be done to
      provide disease-related information and education for patients.

PMID- 23974975
TI  - [Image-guided and -controlled percutaneous laser disc decompression by cross
      sectional imaging and pathology ex vivo].
AB  - INTRODUCTION: Nearly 65-70% of the population over the age of 40 years may be
      affected by lumbar pain. AIM: The aim of the author was to detect the impact of
      percutaneous laser disc decompression in intervertebral discs. METHOD: For the
      model 27 ex vivo lumbar intervertebral discs were used. Constant laser light
      energy to the nucleus pulposus was delivered using diode laser. Computed
      tomography and fluoroscopy were performed to compare the accuracy of the
      procedure. For the detection of the physical effect of the laser procedure,
      magnetic resonance imaging was performed after the laser procedure. To
      demonstrate morphological tissue changes, histopathological studies were
      conducted. RESULTS: 2 mm accuracy was reached by cross-sectional imaging aided
      surgical navigation. The radiation exposure time to the staff was reduced.
      Measurable tissue changes were detected and different physical effects were
      verified in the nucleus pulposus after the laser procedure magnetic resonance
      imaging. CONCLUSIONS: The applied study is feasible for modeling percutaneous
      laser disk decompression PLDD with cross sectional imaging aided surgical
      navigation. The physical effect was detectable by magnetic resonance measurements
      which could be used to control in vivo human applications in the future.

PMID- 23974977
TI  - Magnetic tumor targeting of beta-glucosidase immobilized iron oxide
      nanoparticles.
AB  - Directed enzyme/prodrug therapy (DEPT) has promising application for cancer
      therapy. However, most current DEPT strategies face shortcomings such as the loss
      of enzyme activity during preparation, low delivery and transduction efficiency
      in vivo and difficultly of monitoring. In this study, a novel magnetic directed
      enzyme/prodrug therapy (MDEPT) was set up by conjugating beta-glucosidase (beta
      Glu) to aminated, starch-coated, iron oxide magnetic iron oxide nanoparticles
      (MNPs), abbreviated as beta-Glu-MNP, using glutaraldehyde as the crosslinker.
      This beta-Glu-MNP was then characterized in detail by size distribution, zeta
      potential, FTIR spectra, TEM, SQUID and magnetophoretic mobility analysis.
      Compared to free enzyme, the conjugated beta-Glu on MNPs retained 85.54% +/- 6.9%
      relative activity and showed much better temperature stability. The animal study
      results showed that beta-Glu-MNP displays preferable pharmacokinetics
      characteristics in relation to MNPs. With an adscititious magnetic field on the
      surface of a tumor, a significant quantity of beta-Glu-MNP was selectively
      delivered into a subcutaneous tumor of a glioma-bearing mouse. Remarkably, the
      enzyme activity of the delivered beta-Glu in tumor lesions showed as high as
      20.123+/-5.022 mU g(-1) tissue with 2.14 of tumor/non-tumor beta-Glu activity. 

PMID- 23974978
TI  - Detection and quantification of intracerebral and intraventricular hemorrhage
      from computed tomography images with adaptive thresholding and case-based
      reasoning.
AB  - PURPOSE:    Hemorrhage within the brain space (HWBS) involves the brain
      parenchyma and ventricle systems, and is associated with high morbidity and
      mortality. Computed tomography (CT) head scans are the recommended modality for
      diagnosis and treatment for HWBS. However, HWBS detection may be difficult when
      the hemorrhage is inconspicuous, while quantification is hard as hemorrhage can
      have very variable intensity that overlaps with normal brain tissue. An algorithm
      is proposed to detect and quantify HWBS. METHODS: Adaptive thresholding and case
      based reasoning (CBR) were applied to HWBS in four steps: preprocessing to
      extract the brain, adaptive thresholding based on local contrast with varied
      window sizes to derive candidate HWBS regions, case representation to represent
      each candidate HWBS region by parameters on context as well as intensity and
      geometrical characteristics, and classification of HWBS by taking each candidate
      HWBS region as a case and applying CBR. Additionally, case base indexing and
      weights optimization were used to increase retrieval speed and improve
      performances. Refinement of each recognized HWBS was performed for quantifying
      HWBS. RESULTS: Validation on 426 clinical CT data indicates that the proposed
      algorithm achieved a detection rate of 94.4 % and recall of 79.2 % for detecting
      HWBS regions. Visually, the HWBS regions calculated from adaptive thresholding
      plus refinement agreed well with expert delineation. For 10 representative data
      with small to large hemorrhage, the algorithm quantitatively yielded a
      segmentation accuracy of [Formula: see text]. Case base indexing increased the
      retrieval speed by 41.1 times at the expense of decreasing detection rate of 0.5
      % and recall of 2.6 %. Genetic algorithm optimization enhanced the detection rate
      and recall to, respectively, 94.9 and 83.5 %. CONCLUSIONS: We developed and
      tested an algorithm that combined adaptive thresholding and CBR for detecting and
      quantifying HWBS. Experiments showed that adaptive thresholding could provide
      suitable candidates, while CBR was able to identify HWBS regions. The proposed
      method has potential as a new tool for accurately detecting and quantifying HWBS.

PMID- 23974979
TI  - Catheter tip tracking for MR-guided interventions using discrete Kalman filter
      and mean shift localization.
AB  - PURPOSE: This paper presents and evaluates stochastic computer algorithms used to
      automatically detect and track marked catheter tip during MR-guided
      catheterization. The algorithms developed employ extraction and matching of
      regional features of the catheter tip to perform the localization. METHOD: To
      perform the tracking, a probability map that indicates the possible locations of
      the catheter tip in the MR images is first generated. This map is generated from
      the similarity to a given marker template. The method to assess the similarity
      between the marker template image and the different positions on each MR frame is
      based on speeded-up robust features extracted from the gradient image. The
      probability map is then used in two different stochastic localization frameworks
      mean shift (MS) localization and Kalman filter (KF) to track the position of the
      catheter using pairs of orthogonal projection of 2D MR images. The algorithm
      developed was tested on catheter tip marked with LC resonant circuit (of size 2
      mm x 2 cm) tuned to the Larmor frequency of the MRI scanner and for different
      image resolutions (1, 3, 5 and 7 mm squared pixel). RESULTS: The tracking
      performance was very robust for the two algorithms MS and KF with image
      resolution as low as 3 mm where the localization error was about 1 mm for KF and
      0.9 mm for MS. For the 5-mm resolution images, the error was 2.2 mm for both KF
      and MS, and for the 7-mm resolution images, the error was 3.6 and 3.7 mm for KF
      and MS, respectively. CONCLUSION: Both KF and MS gave comparable results when it
      comes to accuracy for the different image resolutions. The results showed that
      the two tracking algorithms tracked the catheter tip with high robustness for
      image resolution of 3 mm and with acceptable reliability for image resolution as
      poor as 5 mm with the resonant marker configuration used.

PMID- 23974983
TI  - Organization and regulation of the arsenite oxidase operon of the moderately
      acidophilic and facultative chemoautotrophic Thiomonas arsenitoxydans.
AB  - Thiomonas arsenitoxydans is an acidophilic and facultatively autotrophic
      bacterium that can grow by oxidizing arsenite to arsenate. A comparative genomic
      analysis showed that the T. arsenitoxydans aioBA cluster encoding the two
      subunits of arsenite oxidase is distinct from the other clusters, with two
      specific genes encoding a cytochrome c and a metalloregulator belonging to the
      ArsR/SmtB family. These genes are cotranscribed with aioBA, suggesting that these
      cytochromes c are involved in arsenite oxidation and that this operon is
      controlled by the metalloregulator. The growth of T. arsenitoxydans in the
      presence of thiosulfate and arsenite, or arsenate, is biphasic. Real-time PCR
      experiments showed that the operon is transcribed during the second growth phase
      in the presence of arsenite or arsenate, whereas antimonite had no effect. These
      results suggest that the expression of the aioBA operon of T. arsenitoxydans is
      regulated by the electron donor present in the medium, i.e., is induced in the
      presence of arsenic but is repressed by more energetic substrates. Our data
      indicate that the genetic organization and regulation of the aioBA operon of T.
      arsenitoxydans differ from those of the other arsenite oxidizers. 

PMID- 23974981
TI  - Defective DROSHA processing contributes to downregulation of MiR-15/-16 in
      chronic lymphocytic leukemia.
AB  - The MIR-15A/-16-1 tumor suppressor microRNAs (miRNAs) are deleted in leukemic
      cells from more than 50% of patients with chronic lymphocytic leukemia (CLL). As
      these miRNAs are also less abundant in patients without genomic deletion, their
      downregulation in CLL is likely to be caused by additional mechanisms. We found
      the primary transcripts (pri-miRNAs) of MIR-15a/-16/-15b to be elevated and
      processing intermediates (precursor miRNAs) to be reduced in cells from CLL
      patients (22/38) compared with non-malignant B-cells (n=14), indicating a block
      of miRNA maturation at the DROSHA processing step. Using a luciferase reporter
      assay for pri-miR processing we validated the defect in primary CLL cells. The
      block of miRNA maturation is restricted to specific miRNAs and can be found in
      the cell line MEC-2, but not in MEC-1, even though both are derived from the same
      CLL patient. In these cells, the RNA-specific deaminase ADARB1 leads to reduced
      pri-miRNA processing, but full processing efficiency is recovered upon deletion
      of the RNA-binding domains or nuclear localization of ADARB1. Thus, we show that,
      apart from genomic deletion or transcriptional downregulation, aberrant
      processing of miRNA leads to specific reduction of miRNAs in leukemic cells. This
      represents a novel oncogenic mechanism in the pathogenesis of CLL. 

PMID- 23974984
TI  - The bigger the better: determining nephron size in kidney.
AB  - The main functions of the kidney are to excrete metabolic waste products and
      actively reabsorb essential molecules such as amino acids, ions, glucose and
      water. In humans, a wide range of genetic disorders exist characterized by
      wasting of metabolically important compounds. At the cellular level, more than 20
      highly specialized renal epithelial cell types located in different segments of
      the nephron contribute to the reabsorption process. In particular, proximal
      tubular cells play a crucial role and are uniquely adapted to maximize
      reabsorption efficiency. They accommodate high numbers of transporters and
      channels by increasing the apical surface area in contact with the primary
      filtrate by forming a brush border as well as undergoing hypertrophy and
      hyperplasia. This adaptation is evolutionarily conserved and is detected in the
      primitive pronephric kidney of fish and amphibians as well as the metanephric
      kidney of higher vertebrates. Surprisingly, signaling pathways regulating these
      three processes have remained largely unknown. Here we summarize recent studies
      that highlight the early phases of kidney development as a critical juncture in
      establishing proximal tubule size. 

PMID- 23974985
TI  - Evaluation of the concurrent use of potassium-influencing drugs as risk factors
      for the development of hyperkalemia.
AB  - BACKGROUND: Hyperkalemia is a potentially dangerous electrolyte abnormality with
      a reported incidence of 1-10 % in hospitals. Patients are especially at risk of
      developing this complication if they use a combination of potassium supplements
      and potassium sparing diuretics or renin-angiotensin-aldosterone-system (RAAS)
      inhibitors. Previous studies on the occurrence of hyperkalemia in patients who
      use multiple potassium influencing drugs simultaneously were either small in
      sample size or did not investigate the full range of drugs involved. OBJECTIVE:
      To assess the prevalence of hyperkalemia and to identify risk factors for its
      development in hospitalised patients using potassium supplements, potassium
      sparing diuretics and/or RAAS-inhibitors concurrently. SETTING: The study was
      conducted at the Onze Lieve Vrouwe Hospital in Amsterdam, The Netherlands from
      January 2009 to May 2010. METHOD: A retrospective, nested case-control study
      included hospitalised patients who used a combination of potassium-influencing
      drugs. Cases were patients with serum potassium >= 5.5 mmol/l, controls were
      patients with normal serum potassium levels. Cases and controls were included in
      a ratio of 1:2. The following known risk factors associated with hyperkalemia
      were recorded and statistically analyzed: diabetes mellitus, congestive heart
      failure, decreased renal function, advanced age, gender and use of heparin,
      digoxin, non-steroidal anti-inflammatory drugs, beta-blockers, calcineurin
      antagonists and trimethoprim. MAIN OUTCOME MEASURE: Identify risk factors for the
      development of hyperkalemia as a result of the concurrent use of potassium
      supplements, RAAS inhibitors and/or potassium-sparing diuretics. RESULTS: Of 774
      patients included in this study, 52 patients developed hyperkalemia; a prevalence
      of 6.7 %. The only risk factor found to be significantly associated with
      hyperkalemia was lowered renal function, expressed as estimated glomerular
      filtration rate (eGFR) <50 ml/min (adjusted OR 5.08; 95 % CI 2.46-10.48). None of
      the other tested risk factors was identified as significant. CONCLUSION: This
      study showed that decreased renal function (eGFR <50 ml/min) was associated with
      a fivefold increased risk for hyperkalemia in patients using potassium
      influencing drugs. While previous studies showed that hyperkalemia substantially
      increases below a threshold of eGFR <30 or 40 ml/min, we observed a lower
      threshold of eGFR <50 ml/min. It is therefore recommended that physicians should
      be particularly alert while monitoring the use of potassium-influencing drugs in
      patients with decreased renal function.

PMID- 23974982
TI  - IMWG consensus on risk stratification in multiple myeloma.
AB  - Multiple myeloma is characterized by underlying clinical and biological
      heterogeneity, which translates to variable response to treatment and outcome.
      With the recent increase in treatment armamentarium and the projected further
      increase in approved therapeutic agents in the coming years, the issue of having
      some mechanism to dissect this heterogeneity and rationally apply treatment is
      coming to the fore. A number of robustly validated prognostic markers have been
      identified and the use of these markers in stratifying patients into different
      risk groups has been proposed. In this consensus statement, the International
      Myeloma Working Group propose well-defined and easily applicable risk categories
      based on current available information and suggests the use of this set of
      prognostic factors as gold standards in all clinical trials and form the basis of
      subsequent development of more complex prognostic system or better prognostic
      factors. At the same time, these risk categories serve as a framework to
      rationalize the use of therapies. 

PMID- 23974987
TI  - Towards improving dose administration aid supply: a quality improvement
      intervention aimed at reducing dispensing errors.
AB  - BACKGROUND: There is a risk that medicines can be dispensed into dose
      administration aids (DAAs), inaccurately or unsuitably. Quality improvement
      interventions (QIIs) may target this pharmacy medicine supply service and reduce
      the occurrence of these dispensing errors. In turn, medicine administration can
      improve in nursing homes (NHs) that use these devices. OBJECTIVE: To develop,
      introduce and evaluate the potential of a QII to improve DAA medicine supply.
      SETTING: Fourteen Victorian community pharmacies and 45 NHs. METHODS: A QII was
      developed using findings from three focus groups with 13 participants involved
      with DAAs at community pharmacies and NHs. The intervention was introduced to
      community pharmacies and NHs via a pharmacist-facilitated education session;
      attendees completed an evaluation questionnaire. MAIN OUTCOME MEASURE: Potential
      usefulness and effectiveness of the QII at improving DAA supply and reducing
      dispensing errors. RESULTS: The QII was titled: 'Be alert and work together for
      medicine safety, DAA incident awareness toolkit'. Four-hundred and thirty-five
      questionnaires were returned (85.0 % response rate). Respondents believed the
      intervention had the potential to improve pharmacy medicine supply or NH medicine
      administration involving DAAs 'very' (47.3 % of responses) or 'extremely well'
      (23.4 %). The intervention had the potential to reduce the occurrence of DAA
      dispensing errors 'very' (49.6 %) or 'extremely well' (20.5 %). CONCLUSION: A
      stakeholder informed QII was perceived to have the potential to improve DAA
      medicine supply from community pharmacies to NHs and reduce the occurrence of
      dispensing errors found within them. Future quantitative evaluation of the
      intervention is required.

PMID- 23974988
TI  - Baicalin attenuates brain edema in a rat model of intracerebral hemorrhage.
AB  - Baicalin is a flavonoid compound purified from the roots of Scutellaria
      baicalensis, which possesses multiple biological activities. Previous studies
      have shown that baicalin is protective in ischemic cerebral diseases. The aim of
      the present study was to examine the effects of baicalin on brain injury in a rat
      model of intracerebral hemorrhage (ICH) and to explore the possible mechanisms.
      Intracerebral hemorrhage was induced in male Wistar rats by injection of 0.5 U
      collagenaseVII to the caudate nucleus. Sham operation rats were injected with
      equal volume of saline. After the induction of ICH, the rats were randomly
      divided into four groups and administered with different dose of baicalin (0, 25,
      50, or 100 mg/kg in saline) through peritoneal injection. The brain tissues
      around the hemorrhage areas were collected on days 1, 3, and 5 after treatment.
      Brain edema was analyzed by desiccation method; the metalloproteinase-9 (MMP-9)
      protein and mRNA expression were determined by western blotting and real time RT
      PCR, respectively. Nuclear factor-kappaB (NF-kappaB) protein expression was
      analyzed by western blotting. IL-1beta and IL-6 levels were determined by enzyme
      linked immunosorbent assay. Blood-brain barrier permeability was determined by
      Evans blue leakage method. The results showed that baicalin reduced brain edema
      following ICH in a dose-dependent manner, with concomitant inhibition of NF
      kappaB activation and suppression of MMP-9 expression. In addition, baicalin also
      reduced IL-1beta and IL-6 production, as well as blood-brain barrier
      permeability. The above results indicated that baicalin prevents against
      perihematomal edema development after intracerebral hemorrhage possibly through
      an anti-inflammatory mechanism.

PMID- 23974989
TI  - R-Spondin 1 promotes vibration-induced bone formation in mouse models of
      osteoporosis.
AB  - Bone tissue adapts to its functional environment by optimizing its morphology for
      mechanical demand. Among the mechanosensitive cells that recognize and respond to
      forces in the skeleton are osteocytes, osteoblasts, and mesenchymal progenitor
      cells (MPCs). Therefore, the ability to use mechanical signals to improve bone
      health through exercise and devices that deliver mechanical signals is an
      attractive approach to age-related bone loss; however, the extracellular or
      circulating mediators of such signals are largely unknown. Using SDS-PAGE
      separation of proteins secreted by MPCs in response to low-magnitude mechanical
      signals and in-gel trypsin digestion followed by HPLC and mass spectroscopy, we
      identified secreted proteins up-regulated by vibratory stimulation. We exploited
      a cell senescence-associated secretory phenotype screen and reasoned that a
      subset of vibration-induced proteins with diminished secretion by senescent MPCs
      will have the capacity to promote bone formation in vivo. We identified one such
      vibration-induced bone-enhancing (vibe) gene as R-spondin 1, a Wnt pathway
      modulator, and demonstrated that it has the capacity to promote bone formation in
      three mouse models of age-related bone loss. By virtue of their secretory status,
      some vibe proteins may be candidates for pre-clinical development as anabolic
      agents for the treatment of osteoporosis. KEY MESSAGE: Mesenchymal stem cells
      respond to low magnitude mechanical signals (vibration). R-Spondin 1 is
      upregulated by mechanical signals and secreted. R-Spondin 1 promotes bone
      formation in three mouse models of osteoporosis.

PMID- 23974990
TI  - FUS-mediated alternative splicing in the nervous system: consequences for ALS and
      FTLD.
AB  - Mutations in fused in sarcoma (FUS) in a subset of patients with amyotrophic
      lateral sclerosis (ALS) linked this DNA/RNA-binding protein to neurodegeneration.
      Most of the mutations disrupt the nuclear localization signal which strongly
      suggests a loss-of-function pathomechanism, supported by cytoplasmic inclusions.
      FUS-positive neuronal cytoplasmic inclusions are also found in a subset of
      patients with frontotemporal lobar degeneration (FTLD). Here, we discuss recent
      data on the role of alternative splicing in FUS-mediated pathology in the central
      nervous system. Several groups have shown that FUS binds broadly to many
      transcripts in the brain and have also identified a plethora of putative splice
      targets; however, only ABLIM1, BRAF, Ewing sarcoma protein R1 (EWSR1),
      microtubule-associated protein tau (MAPT), NgCAM cell adhesion molecule (NRCAM),
      and netrin G1 (NTNG1) have been identified in at least three of four studies.
      Gene ontology analysis of all putative targets unanimously suggests a role in
      axon growth and cytoskeletal organization, consistent with the altered morphology
      of dendritic spines and axonal growth cones reported upon loss of FUS. Among the
      axonal targets, MAPT/tau and NTNG1 have been further validated in biochemical
      studies. The next challenge will be to confirm changes of FUS-mediated
      alternative splicing in patients and define their precise role in the
      pathophysiology of ALS and FTLD. 

PMID- 23974991
TI  - Nationwide temporal trends in incidence of hospitalization and surgical
      intestinal resection in pediatric inflammatory bowel diseases in the United
      States from 1997 to 2009.
AB  - BACKGROUND: Data are limited on temporal trends in outcomes of hospitalization
      and surgery in pediatric Crohn's disease (CD) and ulcerative colitis (UC). Thus,
      we evaluated the U.S. nationwide temporal trends for incidence of hospitalization
      and intestinal resection along with associated resource utilization. METHODS: We
      used the Kids' Inpatient Database (1997, 2000, 2003, 2006, and 2009) to identify
      all admissions for children aged 18 years or younger with a primary CD
      (International Classification of Diseases, Ninth Revision [ICD-9]: 555.X) or UC
      (ICD-9: 556.X) diagnosis or a secondary CD or UC diagnosis and procedural code of
      intestinal resection. Poisson regression analysis was performed to evaluate time
      trends in the incidence of hospitalization, intestinal resection, and hospital
      resource utilization. RESULTS: The annual incidence of hospitalization was 5.7
      and 3.5 per 100,000 children for CD and UC, respectively, with significant
      increases over time for CD (annual percent increase [API], 3.8%; 95% confidence
      interval [CI], 3.0%-4.5%) and UC (API, 4.5%; 95% CI, 4.3%-4.7%). Median hospital
      days per hospitalization for CD and UC remained stable, whereas median charge per
      hospitalization increased for CD (API, 4.1%; 95% CI, 2.6%-5.6%) and UC (API,
      4.7%; 95% CI, 3.5%-5.9%). The annual incidence of intestinal resection remained
      stable for UC at 0.6 per 100,000 children but climbed for CD (API, 2.1%; 95% CI,
      0.1-4.2). CONCLUSIONS: The annual incidence of hospitalization is climbing in
      pediatric inflammatory bowel diseases, accompanied by rising intestinal resection
      rates for CD and stable colectomy rates for UC. With escalating resource
      utilization, the economic and health burden of pediatric inflammatory bowel
      diseases is substantial.

PMID- 23974992
TI  - Report of the CCFA pediatric bone, growth and muscle health workshop, New York
      City, November 11-12, 2011, with updates.
AB  - Growth retardation, delayed puberty, decreased bone mass, altered bone
      architecture, hypovitaminosis D and skeletal muscle mass deficits are common in
      children with inflammatory bowel diseases. The Crohn's and Colitis Foundation of
      America sponsored a multidisciplinary workshop on the subject of Bone and
      Skeletal Growth in Pediatric IBD, held in New York City in November 2011. The
      topic of the workshop was a key recommendation of the Foundation's Pediatric
      Challenges meeting in 2005. The Litwin Foundation provided a generous grant to
      support this crucial research and workshop through the CCFA. The workshop
      featured 15 presentations by researchers from the United States, Canada,
      Switzerland, Germany, and the United Kingdom and a number of posters elucidating
      diverse aspects of the problem of growth retardation and compromised bone health
      in pediatric Crohn's disease and ulcerative colitis. The workshop comprised
      original, basic, and clinical research and relevant reviews of underlying
      genetics, molecular biology, endocrinology, immunology, and bone physiology
      research. Investigators funded by CCFA and the Litwin Family Foundation are
      marked by an asterisk after their name in the text. Workshop presentations fell
      under 3 broad categories: "Mechanisms of Suppression and Growth of Bone Cell
      Function by Inflammation," "Impact of IBD on Growth and Bone Health," and
      "Approaches to Address Growth Failure and Low Bone Mass in Children with IBD,"
      summarized herein. We have cited the publications that resulted from this
      granting mechanism in the appropriate section and references for pertinent
      updates on each topic.

PMID- 23974994
TI  - Replication study of ulcerative colitis risk loci in a Lithuanian-Latvian case
      control sample.
AB  - BACKGROUND: Differences between populations might be reflected in their different
      genetic risk maps to complex diseases, for example, inflammatory bowel disease.
      We here investigated the role of known inflammatory bowel disease-associated
      single nucleotide polymorphisms (SNPs) in a subset of patients with ulcerative
      colitis (UC) from the Northeastern European countries Lithuania and Latvia and
      evaluated possible epistatic interactions between these genetic variants.
      METHODS: We investigated 77 SNPs derived from 5 previously published genome-wide
      association studies for Crohn's disease and UC. Our study panel comprised 444
      Lithuanian and Latvian patients with UC and 1154 healthy controls. Single marker
      case-control association and SNP-SNP epistasis analyses were performed. RESULTS:
      We found 14 SNPs tagging 9 loci, including 21q21.1, NKX2-3, MST1, the HLA region,
      1p36.13, IL10, JAK2, ORMDL3, and IL23R, to be associated with UC. Interestingly,
      the association of UC with previously identified variants in the HLA region was
      not the strongest association in our study (P = 4.34 * 10, odds ratio [OR] =
      1.25), which is in contrast to all previously published studies. No association
      with any disease subphenotype was found. SNP-SNP interaction analysis showed
      significant epistasis between SNPs in the PTPN22 (rs2476601) and C13orf31
      (rs3764147) genes and increased risk for UC (P = 1.64 * 10, OR = 2.44). The
      association has been confirmed in the Danish study group (P = 0.04, OR = 3.25).
      CONCLUSIONS: We confirmed the association of the 9 loci (21q21.1, 1p36.13, NKX2
      3, MST1, the HLA region, IL10, JAK2, ORMDL3, and IL23R) with UC in the Lithuanian
      Latvian population. SNP-SNP interaction analyses showed that the combination of
      SNPs in the PTPN22 (rs2476601) and C13orf31 (rs3764147) genes increase the risk
      for UC.

PMID- 23974996
TI  - A 3-year-old boy with poor vision and bilateral retinal detachment. JXLR.

PMID- 23974995
TI  - Cytomegalovirus infection of the ileoanal pouch: clinical characteristics and
      outcomes.
AB  - BACKGROUND: Up to 30% of cases of pouchitis are felt to have a secondary cause.
      Cytomegalovirus (CMV) may represent a possible etiopathological agent. Here, we
      report our experience with CMV involvement of the pouch, including risk factors,
      clinical features, and pouch outcomes in patients with inflammatory bowel disease
      after proctocolectomy with ileal pouch-anal anastomosis. METHODS: The pathology
      database at Mayo Clinic in Rochester was searched between January 1995 and
      October 2012 for patients with a tissue diagnosis of CMV of the pouch following
      ileal pouch-anal anastomosis. RESULTS: Seven patients with CMV inclusions of the
      pouch were identified. The median age was 35 (range, 10-53) years, and the
      majority were female (71%). Five patients (71%) were on immunosuppressive
      medications including 4 who had undergone orthotopic liver transplantation for
      primary sclerosing cholangitis. The clinical presentation was similar among all
      patients: the majority had diarrhea (86%), fever (71%), and abdominal pain (57%).
      All had mucosal inflammation, with 71% having focal ulcerations in the pouch and
      60% having inflammatory changes in the prepouch ileum. All patients improved with
      ganciclovir. None required pouch excision or had recurrent CMV infection. Three
      patients had recurrent nonspecific pouchitis. CONCLUSIONS: A high index of
      suspicion is needed to diagnose CMV of the pouch. An increase in stool frequency
      and fever in patients on immune suppression or in those who have failed empiric
      antibiotics should prompt assessment for CMV infection. Antiviral therapy seems
      to be effective, and postinfection pouch outcomes seem favorable, particularly in
      those presenting with their first episode of pouchitis.

PMID- 23974993
TI  - The role of macrophages and dendritic cells in the initiation of inflammation in
      IBD.
AB  - In the healthy gastrointestinal tract, homeostasis is an active process that
      requires a careful balance of host responses to the enteric luminal contents.
      Intestinal macrophages and dendritic cells (DCs) comprise a unique group of
      tissue immune cells that are ideally situated at the interface of the host and
      the enteric luminal environment to appropriately respond to microbes and ingested
      stimuli. However, intrinsic defects in macrophage and DC function contribute to
      the pathogenesis of inflammatory bowel diseases, as highlighted by recent genome
      wide association studies. Gastrointestinal macrophages and DCs participate in
      inflammatory bowel disease development through inappropriate responses to enteric
      microbial stimuli, inefficient clearance of microbes from host tissues, and
      impaired transition from appropriate proinflammatory responses to anti
      inflammatory responses that promote resolution. By understanding how intestinal
      macrophages and DCs initiate chronic inflammation, new pathogenesis-based
      therapeutic strategies to treat human inflammatory bowel diseases will be
      elucidated.

PMID- 23974997
TI  - Factors associated with outcomes of pneumatic retinopexy for rhegmatogenous
      retinal detachments: a retrospective review of 422 cases.
AB  - BACKGROUND: To determine the factors associated with anatomical and visual
      outcomes, and complications when using pneumatic retinopexy in the management of
      rhegmatogenous retinal detachments. METHODS: On a whole, 406 patients having
      undergone 422 primary pneumatic retinopexies for the management of rhegmatogenous
      retinal detachment at a tertiary care hospital, between January 2004 and December
      2009, with a minimum follow-up of 3 months were included in this case series.
      Multivariate logistic regression was used to estimate associations of demographic
      and clinical factors with anatomical and visual outcomes. RESULTS: The single
      operation success rate was 60.7%, and final anatomical success was 99.5%. Male
      gender and the presence of complications were associated with single operation
      failure, whereas age over 65 years, poor preoperative visual acuity, the presence
      of complications were associated with poorer visual outcomes. Better preoperative
      visual acuity and absence of complications were associated with obtaining both a
      good visual outcome and anatomical success after a single intervention. The most
      common complications included new or missed tears (16.3%), delayed subretinal
      fluid reabsorption (12.1%), and epiretinal membrane (10.2%). CONCLUSION: Several
      factors are associated with pneumatic retinopexy outcomes for rhegmatogenous
      retinal detachments. These factors should be taken into consideration when
      identifying patients who would benefit from pneumatic retinopexy and those who
      are at risk of requiring additional interventions.

PMID- 23974998
TI  - Transscleral delivery of Nd: YLF laser at 1,047 nm causes vascular occlusion in
      experimental pigmented choroidal melanoma.
AB  - PURPOSE: The aims of this study were to determine the scleral attenuation of
      focused neodymium: yttrium-lanthanum-fluoride laser at 1,047 nm applied
      transsclerally and whether transscleral delivery can close the vascular supply at
      the base of experimental choroidal melanoma in rabbits. METHODS: Fifty-two New
      Zealand albino rabbits were included. Scleral laser attenuation was measured
      across fresh sclera. B16F10 melanomas were established in the subchoroidal space
      of 49 rabbits. Twenty-one animals were killed immediately after transscleral
      treatment, 14 were followed for 2 weeks to 4 weeks, and 14 were followed without
      treatment. Ophthalmoscopy, fundus photographs, and fluorescein angiography were
      performed before treatment, immediately after, and weekly during the follow-up.
      Eyes were examined by light microscopy. RESULTS: Sclera attenuated laser energy
      by 31% +/- 7%. Immediately after treatment, angiography showed diffuse
      hypofluorescence in 71% (15 of 21 rabbits). Light microscopy showed vascular
      occlusion extending at least two thirds of the tumor thickness from the base.
      Seven of the 14 tumors followed for 15 days +/- 8 days were eradicated. There was
      no correlation between tumor height and eradication. CONCLUSION: Rabbit sclera
      attenuated 31% +/- 7% of laser energy. A single transscleral treatment causes
      tumor vascular closure at the base and may serve as an adjuvant therapy to ensure
      destruction of deep and intrascleral tumor cells.

PMID- 23974999
TI  - A lensing effect of inner retinal cysts on images of the photoreceptor mosaic.

PMID- 23975000
TI  - Assessment of the risk of needlestick injuries associated with intravitreal
      injections.
AB  - PURPOSE: To assess the overall risk of needlestick injuries (NSIs) associated
      with intravitreal injection, and more specifically related to the practice of
      compounding pharmacies of applying informational adhesive stickers to repackaged
      bevacizumab injection syringes. METHODS: This cross-sectional study involved an
      online survey of retina specialists in the United States. RESULTS: Of the 717
      invited retina specialists, 158 (22%) responded to the online survey. The
      respondents reported using 1 pair of gloves (51%), no gloves (46%), or 2 pairs of
      gloves (3%) during intravitreal injection. Repackaged bevacizumab syringes
      distributed by compounding pharmacy were used by 89% of the respondents, and 63%
      reported that the adhesive sticker was applied directly to the syringe.
      Unintentional adhesion between the sticker and hand or glove was experienced by
      9% of respondents. At least 1 NSI during intravitreal injection was experienced
      by 8% of respondents, and sticker-related injury was reported by 3%. The sticker
      was perceived to increase risk for NSI by 33% of respondents. CONCLUSION: This
      survey showed that 8% of the responding physicians surveyed have experienced at
      least one NSI during intravitreal injections, of which approximately one third
      was attributed to the adhesive sticker. Direct application of misfitting stickers
      to repackaged syringes by compounding pharmacies may be a practice that can
      aggravate the risk of NSI.

PMID- 23975001
TI  - Does microperimetry have a prognostic value in central serous chorioretinopathy?
AB  - PURPOSE: To investigate the relationship between retinal sensitivity and
      persistence of subretinal fluid and then to analyze microperimetry as a
      prognostic predictor of acute central serous chorioretinopathy. METHODS: A
      prospective observational study. Fourteen eyes of 14 patients presenting with
      first episode acute central serous chorioretinopathy were enrolled and underwent
      ocular examination, spectral domain optical coherence tomography, and MAIA
      microperimetry were performed. After three months of follow-up, without any
      treatment, visual acuity and spectral domain optical coherence tomography macular
      thickness assessments and microperimetry were repeated. The main outcome was to
      find a relation between initial macular sensitivity and persistence of subretinal
      fluid. A receiver operating characteristic curve was plotted to indicate the best
      macular sensitivity cutoff point that would be able to predict whether a patient
      with acute central serous chorioretinopathy would progress to the chronic form.
      According to the cutoff, we calculated the sensitivity, specificity, and positive
      and negative predictive values for macular sensitivity as a method to predict
      persistence of subretinal fluid. RESULTS: On the basis of the receiver operating
      characteristic curve, a cutoff of 20 dB macular sensitivity was obtained, as the
      best balance between sensitivity and specificity to predict chronicity. Using
      this cutoff, the method had a sensitivity of 71% and specificity of 100% with a
      positive predictive value of 100% and negative predictive value of 78%.
      Furthermore, it was found that eyes with acute central serous chorioretinopathy
      and microperimetry of less than 20 dB had a relative risk of 4.5 to develop
      subretinal fluid persistence. CONCLUSION: Microperimetry with a cutoff of 20 dB
      may be a useful test to predict the persistence of subretinal fluid, allowing the
      ophthalmologist to use treatment tools earlier, preventing extracellular damage
      and visual impairment.

PMID- 23975002
TI  - Association between retinal venular dilation and serous retinal detachment in
      diabetic macular edema.
AB  - PURPOSE: To study the relationship between retinal vessel diameter and
      qualitative and quantitative evaluations on spectral-domain optical coherence
      tomography in patients with diabetic macular edema. METHODS: One hundred and
      eight consecutive eyes of 80 patients, with clinically significant macular edema
      underwent optical coherence tomography and color fundus photography. The authors
      evaluated the retinal thickness of the Early Treatment Diabetic Retinopathy Study
      grid and foveal pathomorphologies including cystoid macular edema and serous
      retinal detachment on the optical coherence tomography images. The diameters of
      the superotemporal or inferotemporal retinal vessels originating from the optic
      disk were measured using a computer-assisted technique. RESULTS: The mean
      diameters of the superotemporal and inferotemporal venules were larger in eyes
      with diabetic macular edema than in healthy eyes. The mean diameter of the
      temporal venules but not the arterioles was associated with perifoveal thickening
      in the inferior subfield in eyes with diabetic macular edema (P = 0.014).
      Although the retinal thickening in the central subfield was not correlated with
      the diameters of the retinal vessels, eyes with foveal serous retinal detachment
      had larger mean diameters of superotemporal and inferotemporal venules than those
      without serous retinal detachment (P < 0.001). CONCLUSION: The mean diameters of
      the superotemporal and inferotemporal venules were significantly associated with
      foveal serous retinal detachment in diabetic macular edema.

PMID- 23975003
TI  - Retinal morphologic changes and concentrations of cytokines in eyes with diabetic
      macular edema.
AB  - PURPOSE: To determine the relationship between the retinal morphologic changes
      and concentrations of intravitreal cytokines in eyes with diabetic macular edema.
      METHODS: A retrospective comparative study was performed. The preoperative
      optical coherence tomography images were evaluated to determine the presence of
      serous retinal detachments (SRDs), retinal cystic changes, and retinal swelling.
      The concentrations of vascular endothelial growth factor, interleukin (IL)-6, and
      IL-8 in vitreous samples collected during vitrectomy were determined. The
      correlations between optical coherence tomography parameters, other clinical
      factors, and the concentration of cytokines were calculated. RESULTS: Fifty-two
      eyes (52 patients) were investigated. An SRD was found in 19 of the 52 eyes
      (36.5%). Multivariate regression analysis showed that IL-6 was the only factor
      significantly associated with the presence of an SRD (P = 0.001; odds ratio,
      1.268; 95% confidence interval, 1.105-1.452). The other morphologic changes, such
      as retinal cystic changes and retinal swellings, were not significantly
      associated with the concentrations of intravitreal cytokines. CONCLUSION: The
      significant association of SRD with intravitreal IL-6 indicates that inflammation
      may play an important role in the development of SRD in diabetic macular edema.

PMID- 23975004
TI  - Vitrectomy with or without internal limiting membrane peeling for each stage of
      myopic traction maculopathy.
AB  - PURPOSE: To evaluate the effect of vitrectomy on the best-corrected visual acuity
      (BCVA) and postoperative complications in highly myopic eyes with myopic traction
      maculopathy. METHODS: The medical records of 71 eyes of 64 patients with myopic
      traction maculopathy and high myopia (<=-8.0 diopters and axial length, >=26.0
      mm) were reviewed. Twenty-six eyes had only macular retinoschisis, 30 eyes had
      foveal detachment, and 15 eyes had macular hole. The BCVA and complications were
      studied in eyes that underwent vitrectomy with or without internal limiting
      membrane (ILM) peeling. RESULTS: The postoperative BCVA at the final visit
      significantly improved in the macular retinoschisis and the foveal detachment
      groups (P = 0.003 and P = 0.010, respectively) but not in the macular hole group
      (P = 0.069). The BCVA in the macular retinoschisis group and the foveal
      detachment group with ILM peeling significantly improved at the final visit (P =
      0.003 and P = 0.010, respectively). The BCVA at the final visit significantly
      correlated with age (P = 0.026) and ILM peeling (P = 0.034). A recurrence of
      tractional macular detachment developed more frequently in eyes without ILM
      peeling (P = 0.018). CONCLUSION: These results indicate that vitrectomy with ILM
      peeling can lead to improvement in vision in patients with macular retinoschisis
      or foveal detachment with visual impairments.

PMID- 23975005
TI  - Single incision, outpatient fluid/gas exchange.

PMID- 23975006
TI  - Treatment of anti-vascular endothelial growth factor-resistant diabetic macular
      edema with dexamethasone intravitreal implant.
AB  - PURPOSE: To investigate the efficiency of intravitreal dexamethasone implant in
      patients with chronic diabetic macular edema nonresponsive to three consecutive
      monthly intravitreal injections of anti-vascular endothelial growth factor
      administered previously. METHODS: Fifteen patients (16 eyes) were included in
      this 4-month prospective clinical trial. Main observed outcomes were the changes
      between initial and monthly visits in best-corrected visual acuity, central
      foveal thickness, and intraocular pressure (IOP). Patients included had central
      foveal thickness of >225 MUm (measured by optical coherence tomography) and were
      nonresponsive to previously administered 3 consecutive monthly intravitreal
      injections of 1.25-mg bevacizumab. Administration of intravitreal dexamethasone
      implant was performed at baseline, and patients were followed-up monthly.
      RESULTS: Statistically significant changes from baseline were observed in best
      corrected visual acuity (at 2 months), central foveal thickness (at 1, 2, and 3
      months), and IOP (at Months 1, 2, and 3) as follows: mean best-corrected visual
      acuity significantly increased from 0.29 Snellen lines at baseline to 0.39 lines
      after 2 months (P = 0.0381). At Months 1, 2, and 3, the mean central foveal
      thickness significantly decreased, from 462 MUm at baseline, to 366 MUm (P =
      0.0343), 346 MUm (P = 0.0288), and 355 MUm (P = 0.0370), respectively. When
      compared with baseline IOP of 15.38 mmHg (12-19 mmHg), IOP increased
      significantly at Months 1, 2, and 3: 18.93 mmHg (range, 16-24 mmHg; P = 0.0003),
      19.5 mmHg (range, 16-27 mmHg; P = 0.0003), and 17.5 mmHg (range, 15-21 mmHg; P =
      0.0048), respectively. CONCLUSION: Dexamethasone intravitreal implant may present
      an alternative option in the treatment of chronic diabetic macular edema
      nonresponsive to three consecutive monthly bevacizumab injections administered
      previously. However, IOP measures were only slightly increased. It seems that the
      effect of dexamethasone may last till 4 months after initial injection.

PMID- 23975007
TI  - Rate of sclerotomy suturing in 23-gauge primary vitrectomy.
AB  - PURPOSE: To evaluate the rate of sclerotomy suturing in a large series of primary
      23-gauge vitrectomies. METHODS: Retrospective chart review of 23-gauge
      transconjunctival pars plana vitrectomies performed between 2008 and 2012 in a
      multisurgeon retina practice. Patients with a history of retinal surgery,
      combination of vitrectomy and scleral buckling surgery, or intraoperative
      conversion of a sclerotomy to 20-gauge were excluded from the study. Vitrectomies
      were divided into two types according to their degree of complexity and
      intraoperative use of instrumentation. Demographic and clinical data were
      gathered from the chart. Location and number of sutured sclerotomies were
      obtained from the operative report. RESULTS: A total of 589 eyes from 569
      patients were included in this study. At least 1 sclerotomy was sutured in 227
      eyes (38.5%): 69 (30.4%) had 1 sutured sclerotomy, 52 (22.9%) had 2 sutured
      sclerotomies, and 106 (46.7%) had 3 sutured sclerotomies. Sclerotomy suturing was
      significantly related to the surgical technique (P < 0.001), type of tamponade
      agent (P = 0.048), and complexity of the vitrectomy (P < 0.001). The incidence of
      postoperative hypotony at Day 1 was 2.2% and all cases returned to normal
      intraocular pressure at 1 week. There were no recognized complications related to
      sclerotomies regardless of suturing. CONCLUSION: The factors that increased the
      rate of sclerotomy suturing were the absence of tamponade agent and higher
      complexity of the procedure. There was a high variability in the rate of suturing
      between the surgeons.

PMID- 23975008
TI  - Correspondence.

PMID- 23975009
TI  - Association of pain level, health and wound status in patients with chronic leg
      ulcers.
AB  - Pain is a ubiquitous problem in patients with chronic leg wounds. The pain may be
      caused by the underlying pathology of the leg ulceration, the wound, wound
      treatment, or complications such as skin irritation around the ulcer. The
      objectives of this research were to evaluate the level of suffering endured by
      patients because of their ulcer-related pain, and to evaluate whether and how
      this pain is treated. In addition, to determine whether this pain influences
      quality of life and health status. In 2010, data were collected in order to
      characterize the patients by socio-demographic facts, such as age, gender, co
      morbidity, pathogenesis of the wound, wound status of new patients, wound pain,
      and use of analgesics. In addition, modified EQ-5D questionnaires were
      distributed with additional questions concerning pain experience, treatment, and
      general health status. Of 103 patients, 45 were male and 58 female. Mean age was
      67.8 years (males 65 years, females 70 years). Up to 69% had leg ulcerations due
      to vascular disease. Out of the 103 distributed questionnaires, 49 were returned
      and evaluated. Analysis showed that 82% of these patients reported wound-related
      pain, and 42% estimated their analgesics as not sufficiently pain relieving (mean
      value of the visual analogue scale (VAS) 4.9). Mean health status was 50.5
      (maximal health status 100). Patients with a pain value >= 5 showed a lesser mean
      health status (42.2) than patients with a pain value < 5 (60.3). The proportion
      of patients receiving no, or only weak, analgesics was nearly the same for
      patients with VAS >= 5 and with VAS < 5. Further research in pain therapy is of
      utmost importance to improve the quality of life of patients with chronic wounds.

PMID- 23975010
TI  - MEK inhibition in the treatment of advanced melanoma.
AB  - The RAS-RAF-MEK-ERK pathway is considered to be the most important signal
      transduction pathway in melanoma, and alterations in this pathway via various
      genetic mutations, such as BRAF and NRAS mutations, are known to be important
      drivers of melanomagenesis. As MEK is an essential intermediary kinase protein
      within this pathway, inhibition of MEK has been of a great interest as a
      molecular target therapy in melanoma. In fact, trametinib, a selective MEK
      inhibitor, has been shown to have a survival benefit over cytotoxic chemotherapy
      in patients with V600 BRAF-mutant metastatic melanoma, leading to the FDA
      approval for this patient population. MEK inhibitors may also be useful in
      treatment of advanced melanoma harboring other genetic mutations, such as NRAS
      and GNAQ/GNA11 mutations. Here, we review and discuss the preclinical and
      clinical data regarding MEK inhibitors and their role in the treatment of
      advanced melanoma.

PMID- 23975011
TI  - Process of aerenchyma formation and reactive oxygen species induced by
      waterlogging in wheat seminal roots.
AB  - The development and regulation of aerenchyma in waterlogged conditions were
      studied in the seminal roots of wheat. Evans blue staining and the first cell
      death position indicated that the cortical cell death began at the root mid
      cortex cells in flooding conditions. Continuous waterlogging treatment caused the
      spread of cell death from the mid-cortex to the neighboring cells and well
      developed aerenchyma was formed after 72 h. Meanwhile, the formation of radial
      oxygen loss barrier was observed in the exodermis owing to the induction of
      Casparian bands and lignin deposition. Analysis of aerenchyma along the wheat
      root revealed that aerenchyma formed at 10 mm from the root tip, significantly
      increased toward the center of the roots, and decreased toward the basal region
      of the root. In situ detection of radial oxygen species (ROS) showed that ROS
      accumulation started in the mid-cortex cells, where cell death began indicating
      that cell death was probably accompanied by ROS production. Further waterlogging
      treatments resulted in the accumulation of ROS in the cortical cells, which were
      the zone for aerenchyma development. Accumulation and distribution of H2O2 at the
      subcellular level were revealed by ultracytochemical localization, which further
      verified the involvement of ROS in the cortical cell death process (i.e.,
      aerenchyma formation). Furthermore, gene expression analysis indicated that ROS
      production might be the result of up-regulation of genes encoding for ROS
      producing enzymes and the down-regulation of genes encoding for ROS-detoxifying
      enzymes. These results suggest that aerenchyma development in wheat roots starts
      in the mid-cortex cells and its formation is regulated by ROS.

PMID- 23975012
TI  - T-DNA transfer and T-DNA integration efficiencies upon Arabidopsis thaliana root
      explant cocultivation and floral dip transformation.
AB  - T-DNA transfer and integration frequencies during Agrobacterium-mediated root
      explant cocultivation and floral dip transformations of Arabidopsis thaliana were
      analyzed with and without selection for transformation-competent cells. Based on
      the presence or absence of CRE recombinase activity without or with the CRE T-DNA
      being integrated, transient expression versus stable transformation was
      differentiated. During root explant cocultivation, continuous light enhanced the
      number of plant cells competent for interaction with Agrobacterium and thus the
      number of transient gene expression events. However, in transformation competent
      plant cells, continuous light did not further enhance cotransfer or cointegration
      frequencies. Upon selection for root transformants expressing a first T-DNA, 43
      69 % of these transformants showed cotransfer of another non-selected T-DNA in
      two different light regimes. However, integration of the non-selected
      cotransferred T-DNA occurred only in 19-46 % of these transformants, indicating
      that T-DNA integration in regenerating root cells limits the transformation
      frequencies. After floral dip transformation, transient T-DNA expression without
      integration could not be detected, while stable T-DNA transformation occurred in
      0.5-1.3 % of the T1 seedlings. Upon selection for floral dip transformants with a
      first T-DNA, 8-34 % of the transformants showed cotransfer of the other non
      selected T-DNA and in 93-100 % of them, the T-DNA was also integrated. Therefore,
      a productive interaction between the agrobacteria and the female gametophyte,
      rather than the T-DNA integration process, restricts the floral dip
      transformation frequencies.

PMID- 23975013
TI  - Heart failure outcomes based on race and gender of patients in a medically
      undeserved area.
AB  - The purpose of this descriptive study was to investigate changes in quality of
      life (QoL), disease severity and exercise tolerance of heart failure (HF)
      patients in a medically underserved clinic based on race and gender. Despite
      advances in the treatment of HF over the past decade, incidence, morbidity and
      mortality for patients continue to rise while QoL declines. HF is common in
      African-Americans and women; however, there is limited research focusing on race
      and gender variables. Health related QoL, disease severity measured by B-type
      natriuretic peptide blood test (BNP) and ejection fraction (EF), and exercise
      tolerance measured by six minute walk test (6MWT) were assessed at admission and
      at 6 months in a convenience sample of 53 patients. Variables were compared by
      race and gender. The sample was 67.9% African American and 62.3% male. Men had
      greater improvements than women in QoL, BNP, and EF, while women had greater
      improvements in the 6MWT. African Americans had greater improvements than Whites
      in all four variables. Even in the presence of disease severity in patients with
      New York Heart Association (NYHA) Class III and IV HF, there were significant
      improvements in QoL, BNP, HF outcomes demonstrating the importance of developing
      culturally sensitive and gender-specific treatment plans.

PMID- 23975014
TI  - Breast cancer screening interventions for Arabic women: a literature review.
AB  - Similar to other Middle Eastern countries, breast cancer is the most common
      cancer among women in Qatar with increasing incidence and mortality rates. High
      mortality rates of breast cancer in the Middle Eastern countries are primarily
      due to delayed diagnosis of the disease. Thus screening and early detection of
      breast cancer are important in reducing cancer morbidity and mortality. With the
      aim of updating knowledge on existing interventions and developing effective
      intervention programs to promote breast cancer screening in Arabic populations in
      Qatar, this review addresses the question: What interventions are effective in
      increasing breast cancer knowledge and breast cancer screening rates in Arabic
      populations in Arabic countries and North America? Systematic literature review
      was performed to answer the proposed question. As the result of the search, six
      research studies were identified and appraised. From the findings, we infer
      several insights: (a) a language-appropriate and culturally sensitive educational
      program is the most important component of a successful intervention regardless
      of the study setting, (b) multi-level interventions that target both women, men,
      health care professionals, and/or larger health care system are more likely to be
      successful than single educational interventions or public awareness campaigns,
      and (c) more vigorous, personal and cognitive interventions that address
      psychosocial factors are likely to be more effective than less personal and
      informative interventions. This review has important implications for health care
      providers, intervention planners, and researchers. 

PMID- 23975015
TI  - Clinical analysis of liver fibrosis in choledochal cyst.
AB  - PURPOSE: Although most patients with choledochal cyst (CC) have a favorable
      prognosis with prompt treatment, some of them are complicated with liver
      fibrosis, resulting in prolonged liver dysfunction even after definitive surgery.
      The aim of this study was to distinguish the high-risk group of liver fibrosis in
      patients with CC. METHODS: Fifteen patients who underwent liver biopsy during
      surgery for CC from 1981 to 2012 were enrolled in this study. Liver histology
      with H&E staining was graded according to Ohkuma's classification, and the
      correlation with the clinical characteristics was retrospectively assessed.
      RESULTS: Their median age at biopsy was 13.4 months (range 1-42 months), and
      there were 7 in Ia, 2 in Ic, and 6 in IVa of the Todani classification. There
      were no significant differences in serum liver function test among those cyst
      types. The histological grades of liver fibrosis were as follows: grade 0 (no
      fibrosis) in 7 patients, grade 1 (mild) in 2, grade 2 (moderate) in 3, grade 3
      (severe) in 2, grade 4 (cirrhosis) in 1. All 3 patients with grade 3 and 4 had CC
      with IVa and were under 18-month old. A 3-month-old girl with cirrhosis presented
      with severe jaundice resulting in living-donor liver transplantation despite bile
      drainage. A 16-month-old girl with grade 3 suffered from prolonged liver
      dysfunction and intractable ascites after surgery. CONCLUSIONS: The progression
      of liver fibrosis is likely to be correlated with IVa, and the postoperative
      course might be unsatisfactory in advanced cases. The prompt surgical
      intervention is recommended especially for neonatal and infantile cases with type
      IVa cyst because irreversible liver cirrhosis could occur as early as in the
      infantile period.

PMID- 23975016
TI  - Single-incision laparoscopic-assisted appendectomy in children: exteriorization
      of the appendix is a key component of a simple and cost-effective surgical
      technique.
AB  - PURPOSE: Single-incision laparoscopic appendectomy was recently introduced as a
      less-invasive surgical technique than existing methods, and is increasingly being
      performed worldwide. We have started to perform transumbilical laparoscopic
      assisted appendectomy (TULAA) in children. In this study, we assessed its
      feasibility, efficacy, and cost-effectiveness compared with conventional
      multiport laparoscopic appendectomy (MLA). METHODS: We retrospectively reviewed
      all of the patients who underwent MLA or TULAA between August 2009 and December
      2012. Patient characteristics, operative time, length of hospital stay,
      postoperative complications, cost-effectiveness, and cosmetic results were
      analyzed. RESULTS: A total of 88 patients underwent laparoscopic appendectomy,
      with MLA in 48 patients and TULAA in 40 patients. TULAA was successful in 36/40
      patients. There were no significant differences in mean operative time or mean
      length of stay between the two groups of patients. There were no postoperative
      complications in the TULAA group. The cost of TULAA was much lower than that of
      MLA. TULAA also provided nearly scarless surgery. CONCLUSION: TULAA, in which the
      appendix is exteriorized via a combination of open and laparoscopic techniques,
      is a safe and effective procedure for treating appendicitis in children. TULAA is
      a cost-effective treatment that provides excellent cosmetic results.

PMID- 23975018
TI  - Isolated hypoganglionosis: results of a nationwide survey in Japan.
AB  - PURPOSE: This study analyzes how isolated hypoganglionosis (IH) is diagnosed and
      treated in Japanese pediatric surgical departments. METHODS: A second
      questionnaire was sent to 90 pediatric surgical departments that took part in an
      initial survey on variant Hirschsprung's disease. RESULTS: Of 109 cases
      registered as having a certain diagnosis of IH, we targeted 90 patients and
      excluded the remaining 19. Symptom onset was neonatal ileus with a male:female
      ratio of 34:56. In most cases, results from radio-contrast enemas and suction
      rectal biopsies were normal. Anorectal manometry demonstrated that there was no
      relaxation in 73 % of the 37 patients examined. Furthermore, out of 55 patients
      who were examined intraoperatively, IH was diagnosed or suspected in 29 cases.
      Another 12 cases were eventually diagnosed with IH by other institutions using
      paraffin-embedded specimens. Stomas were initially created in 89 out of 90 cases
      and the mortality rate of the group that initially received jejunostomies was
      significantly lower than that of the ileostomy group (p < 0.05). CONCLUSION:
      Preoperative diagnosis of IH is often difficult and intraoperative biopsies were
      only able to provide a correct diagnosis in 52 % of cases. More accurate
      diagnosis and the initial creation of jejunostomies rather than ileostomies may
      assist in improving patient management and outcomes.

PMID- 23975017
TI  - Life-threatening risk factors and the role of intestinal transplantation in
      patients with intestinal failure.
AB  - PURPOSE: We elucidated the life-threatening risk factors for intestinal failure
      (IF) and characterized the role of intestinal transplantation (ITx) in affected
      patients. METHODS: We conducted a retrospective review of 38 patients with short
      bowel (SB) and 19 with motility disorders (MD). The SB patients were divided into
      three categories according to the length of their residual small bowel and the
      presence of the ileocecal valve. The four disease subcategories were grouped into
      two categories: low-risk category (mild and moderated SB) and high-risk category
      (extensive SB and MD). The age at the introduction of parenteral nutrition (PN)
      was <1 year in 50 patients (infant group, IG) and 1-15 years in 7 patients
      (pediatric group, PG). RESULTS: Enteral autonomy was rarely achieved in the high
      risk category (p < 0.0001). IG was associated with a higher incidence of
      developing intestinal failure-associated liver disease (IFALD) (p = 0.004). Eight
      patients died, due to IFALD in four, sepsis in three and acute heart failure in
      one. Twenty-eight patients (49 %) are currently alive without PN, including four
      after ITx. CONCLUSION: The treatment of high-risk IF is still challenging.
      Inclusion of ITx in appropriate timing, along with aggressive medical,
      nutritional and surgical management, may reduce advanced morbidity and mortality
      of high-risk IF.

PMID- 23975019
TI  - Assessment of suturing in the vertical plane shows the efficacy of the multi
      degree-of-freedom needle driver for neonatal laparoscopy.
AB  - PURPOSE: We have developed a thin needle driver with multiple degrees-of-freedom
      (DOFs) for neonatal laparoscopic surgery. The tip of this needle driver has three
      DOFs for grasp, deflection and rotation. Our aim was to evaluate the performance
      of the multi-DOF needle driver in vertical plane suturing. METHODS: Six pediatric
      surgeons performed four directional suturing tasks in the vertical plane using
      the multi-DOF needle driver and a conventional one. Assessed parameters were the
      accuracy of insertion and exit, the depth of suture, the inclination angle of the
      needle and the force applied on the model. RESULTS: In left and right direction
      sutures, the inclination angle of the needle with the multi-DOF needle driver was
      significantly smaller than that with the conventional one (p = 0.014, 0.042,
      respectively). In left and right direction sutures, the force for pulling the
      model with the multi-DOF needle driver was smaller than that with the
      conventional one (p = 0.036, 0.010, respectively). CONCLUSION: This study showed
      that multi-directional suturing on a vertical plane using the multi-DOF needle
      driver had better needle trajectories and was less invasive as compared to a
      conventional needle driver.

PMID- 23975020
TI  - Impact of the current organ allocation system for deceased donor liver
      transplantation on the outcomes of pediatric recipients: a single center
      experience in Japan.
AB  - PURPOSE: The aim of this study was to analyze the outcomes of children added to
      the waiting list for deceased donor liver transplantation (DDLT) and the results
      of DDLT in a single Japanese center. METHODS: Forty-seven children were listed on
      the organ allocation system for DDLT. The priority points related to the medical
      status of each patient were evaluated and stratified into four categories; 10, 8,
      6, and 3 points. The clinical data were collected from the medical records, and
      the outcomes were analyzed. RESULTS: There were 10 priority points in 25
      patients, 6 points in 13 and 3 points in 9. Ten recipients (21.3 %); 7 patients
      with 10 points and 3 patients with 6 points, underwent DDLT. Seven out of the 10
      recipients received split/reduced liver grafts. The surgical complications
      consisted of biliary stricture, hepatic venous outflow obstruction,
      intraabdominal abscess and intraabdominal bleeding. Two recipients, who were
      critically-ill before DDLT, died due to sepsis. The one-year graft survival rate
      was 70.0 %, with a median follow-up period of 6.4 months. CONCLUSION: The initial
      experience with pediatric DDLT in our series was satisfactory. Split LT of
      deceased donor organs may have the potential to resolve the serious organ
      shortage in Japan.

PMID- 23975021
TI  - Effect of abnormal notochord delamination on hindgut development in the
      Adriamycin mouse model.
AB  - BACKGROUND: Adriamycin mouse model (AMM) is a model of VACTERL anomalies. Sonic
      hedgehog (Shh) pathway, sourced by the notochord, is implicated of anorectal
      malformations. We hypothesized hindgut anomalies observed in the AMM are the
      result of abnormal effect of the notochord. METHODS: Time-mated CBA/Ca mice
      received two intraperitoneal injections of Adriamycin (6 mg/kg) or saline as
      control on embryonic day (E) 7 and 8. Fetuses were harvested from E9 to E11,
      stained following whole mount in situ hybridization with labeled RNA probes to
      detect Shh and Fork head box F1(Foxf1) transcripts. Immunolocalization with
      endoderm marker Hnf3beta was used to visualize morphology. Embryos were scanned
      by OPT to obtain 3D representations of expressions. RESULTS: In AMM, the
      notochord was abnormally displaced ventrally with attachment to the hindgut
      endoderm in 71 % of the specimens. In 32 % of the treated embryos abnormal
      hindgut ended blindly in a cystic structure, and both of types were remarked in
      29 % of treated embryos. Endodermal Shh and mesenchymal Foxf1 genes expression
      were preserved around the hindgut cystic malformation. CONCLUSIONS: The
      delamination of the developing notochord in the AMM is disrupted, which may
      influence signaling mechanisms from the notochord to the hindgut resulting in
      abnormal patterning of the hindgut.

PMID- 23975022
TI  - Redo esophageal surgery: the diagnosis and management of recurrent
      tracheoesophageal fistula.
AB  - This article presents a 30-year review of 38 recurrent tracheoesophageal
      fistulas. The initial 26 cases were presented in 2009 at the annual meeting of
      the British Association of Pediatric Surgeons and the European Association of
      Pediatric Surgeons Joint Conference and published in the Journal of Pediatric
      Surgery (Bruchet al. J Pediatr Surg 45:337-340, 2010). In the initial cohort of
      26 patients, 18 had a leak after their primary operation and 22 had respiratory
      symptoms leading to the discovery of the recurrent fistula. The diagnosis was
      made by a contrast study in 24. The repairs entailed replacing a catheter through
      the fistula, separating the trachea and esophagus completely using sharp
      dissection and placing vascularized tissue, either pleura or pericardium between
      the suture lines. Postoperative complications included seven anastomotic leaks,
      four strictures and three recurrent fistulas. Long-term follow-up (median of 84
      months) showed that 21 took all of their nutrition by mouth, three were tube fed
      and two required a combination of both. Of the 23 patients with growth chart
      data, 16 fell into the first quartile of the growth chart, whereas none fell
      between the 75th and 100th percentile. In conclusion, this initial series of 26
      patients along with the updated additional series of 12 patients is the largest
      series thus far reported in the literature. All 38 patients represent the
      characteristics of recurrent tracheoesophageal fistulas, including techniques to
      make the diagnosis and to provide a secure closure of the fistula, and the long
      term outcomes of these patients. 

PMID- 23975023
TI  - Internationalization: the Hong Kong-China experience as a model for collaborative
      education in Asia.
AB  - PURPOSE: The Hong Kong model for collaboration in education in Asia is based on
      internationalization. Hong Kong benefits from being an international city
      combining an Eastern heritage and a Western society. The University of Hong Kong
      ranks among the world's top 25 universities (2012/2013 QS world university
      rankings), and its Division of Paediatric Surgery has an international reputation
      in research and training. In the past two decades, Hong Kong has leading roles in
      major international pediatric surgical organizations including Pacific
      Association of Pediatric Surgeons, International Pediatric Endosurgery Group,
      Asian Association of Pediatric Surgeons and World Federation of Associations of
      Pediatric Surgeons. While Hong Kong has close collaboration with Japan and other
      advanced economies, the talk will focus on our transfer of international
      experience to Mainland China. METHODS AND RESULTS: (1) A Train-the-Trainer scheme
      consisting of a 1-year structured education program for next-generation leaders
      from selected centers enabled replication and proliferation of similar training
      nationwide. (2) A series of laparoscopic workshops resulted in training of over
      1,300 surgeons in basic and advanced skills in minimally invasive surgery within
      5 years and the establishment of a national specialist organization overseeing
      development and quality assurance. (3) A series of Cross-Strait Symposia on
      Pediatric Oncology established the foundation of multidisciplinary, multicenter
      collaboration in education and research in Mainland China, Taiwan and Hong Kong.
      (4) Initiation of a scientific writing course will enhance surgical research and
      training in China. CONCLUSION: The Hong Kong experience may serve as a model of
      collaboration with other developing economies in Asia.

PMID- 23975024
TI  - A man with recurrent right-sided epistaxis. Angiomyolipoma (AML) of the nasal
      cavity.

PMID- 23975025
TI  - Simultaneous PET-MRI reveals brain function in activated and resting state on
      metabolic, hemodynamic and multiple temporal scales.
AB  - Combined positron emission tomography (PET) and magnetic resonance imaging (MRI)
      is a new tool to study functional processes in the brain. Here we study brain
      function in response to a barrel-field stimulus simultaneously using PET, which
      traces changes in glucose metabolism on a slow time scale, and functional MRI
      (fMRI), which assesses fast vascular and oxygenation changes during activation.
      We found spatial and quantitative discrepancies between the PET and the fMRI
      activation data. The functional connectivity of the rat brain was assessed by
      both modalities: the fMRI approach determined a total of nine known neural
      networks, whereas the PET method identified seven glucose metabolism-related
      networks. These results demonstrate the feasibility of combined PET-MRI for the
      simultaneous study of the brain at activation and rest, revealing comprehensive
      and complementary information to further decode brain function and brain
      networks. 

PMID- 23975026
TI  - Thioredoxin-interacting protein regulates insulin transcription through microRNA
      204.
AB  - Beta-cell dysfunction and impaired insulin production are hallmarks of diabetes,
      but despite the growing diabetes epidemic, the molecular mechanisms underlying
      this disease have remained unclear. We identified thioredoxin-interacting protein
      (TXNIP), a cellular redox regulator, as a crucial factor in beta-cell biology and
      show that beta-cell TXNIP is upregulated in diabetes, whereas TXNIP deficiency
      protects against diabetes by preventing beta-cell apoptosis. Here we show that
      TXNIP and diabetes induce beta-cell expression of a specific microRNA, miR-204,
      which in turn blocks insulin production by directly targeting and downregulating
      MAFA, a known insulin transcription factor. In particular, we first discovered
      the regulation of miR-204 by TXNIP by microarray analysis, followed by validation
      studies in INS-1 beta cells, islets of Txnip-deficient mice, diabetic mouse
      models and primary human islets. We then further found that TXNIP induces miR-204
      by inhibiting the activity of signal transducer and activator of transcription 3
      (STAT3), a transcription factor that is involved in miR-204 regulation. We also
      identified MAFA as a target that is downregulated by miR-204. Taken together, our
      results demonstrate that TXNIP controls microRNA expression and insulin
      production and that miR-204 is involved in beta-cell function. The newly
      identified TXNIP-miR-204-MAFA-insulin pathway may contribute to diabetes
      progression and provides new insight into TXNIP function and microRNA biology in
      health and disease. 

PMID- 23975028
TI  - Identification and characterization of psoralen and isopsoralen as potent CYP1A2
      reversible and time-dependent inhibitors in human and rat preclinical studies.
AB  - Naturally occurring furanocoumarin compounds psoralen (PRN) and isopsoralen
      (IPRN) are bioactive constituents found in herbaceous plants. They are widely
      used as active ingredients in several Chinese herbal medicines. In this study,
      the CYP1A2 inhibitory potential of PRN and IPRN was investigated in rats in vitro
      and in vivo as well as in human liver microsomes. Both compounds exhibited
      reversible and time-dependent inhibition toward rat microsomal cyp1a2. The
      IC(50), k(inact), and K(I) values were 10.4 +/- 1.4 MUM, 0.060 +/- 0.002 min(-1),
      and 1.13 +/- 0.12 MUM for PRN, and 7.1 +/- 0.6 MUM, 0.10 +/- 0.01 min(-1), and
      1.95 +/- 0.31 MUM for IPRN, respectively. In human liver microsomal incubations,
      potent reversible CYP1A2 inhibition was observed for both compounds, with IC(50)
      values of 0.26 +/- 0.01 MUM and 0.22 +/- 0.03 MUM for PRN and IPRN, respectively.
      However, time-dependent inhibition was only observed for IPRN, with kinact and KI
      values of 0.050 +/- 0.002 min(-1) and 0.40 +/- 0.06 MUM, respectively.
      Coadministration with PRN or IPRN significantly inhibited cyp1a2 activity in
      rats, with the area under the curve (AUC) of phenacetin increasing more than 5
      fold. Simcyp simulation predicted that PRN would cause 1.71- and 2.12-fold
      increases in the phenacetin AUC in healthy volunteers and smokers, respectively.
      IPRN, on the other hand, would result in 3.24- and 5.01-fold increases in
      phenacetin AUCs in healthy volunteers and smokers, respectively. These findings
      represent the first detailed report comparing the potential drug-drug
      interactions of PRN and IPRN, and provide useful information for balancing safe
      and efficacious doses of PRN and IPRN.

PMID- 23975027
TI  - Mapping the zebrafish brain methylome using reduced representation bisulfite
      sequencing.
AB  - Reduced representation bisulfite sequencing (RRBS) has been used to profile DNA
      methylation patterns in mammalian genomes such as human, mouse and rat. The
      methylome of the zebrafish, an important animal model, has not yet been
      characterized at base-pair resolution using RRBS. Therefore, we evaluated the
      technique of RRBS in this model organism by generating four single-nucleotide
      resolution DNA methylomes of adult zebrafish brain. We performed several
      simulations to show the distribution of fragments and enrichment of CpGs in
      different in silico reduced representation genomes of zebrafish. Four RRBS brain
      libraries generated 98 million sequenced reads and had higher frequencies of
      multiple mapping than equivalent human RRBS libraries. The zebrafish methylome
      indicates there is higher global DNA methylation in the zebrafish genome compared
      with its equivalent human methylome. This observation was confirmed by RRBS of
      zebrafish liver. High coverage CpG dinucleotides are enriched in CpG island
      shores more than in the CpG island core. We found that 45% of the mapped CpGs
      reside in gene bodies, and 7% in gene promoters. This analysis provides a roadmap
      for generating reproducible base-pair level methylomes for zebrafish using RRBS
      and our results provide the first evidence that RRBS is a suitable technique for
      global methylation analysis in zebrafish.

PMID- 23975030
TI  - Schematic pancreatic configuration: a risk assessment for postoperative
      pancreatic fistula after pancreaticoduodenectomy.
AB  - INTRODUCTION: Postoperative pancreatic fistula (POPF) remains a serious
      complication after pancreaticoduodenectomy (PD). Preoperative risk assessment of
      POPF is desirable in careful preparation for operation. The aim of this study was
      to assess simple and accurate risk factors for clinically relevant POPF based on
      a schematic understanding of the pancreatic configuration using preoperative
      multidetector computed tomography. METHODS: Three hundred and eighteen
      consecutive patients who underwent PD in the National Cancer Center Hospital East
      between November 2006 and March 2013 were investigated. Pre-, intra-, and
      postoperative clinicopathological findings as well as pancreatic configuration
      data were analyzed for the risk of clinically relevant POPF. POPF was defined
      according to the International Study Group of Pancreatic Fistula classification.
      POPF grade A occurred in 52 patients (16.4%), grade B in 84 (26.4%), and grade C
      in 6 (1.9%). CONCLUSIONS: Independent risk factors for POPF grade B/C included
      main pancreatic duct diameter (MPDd) < 2 mm (P = 0.001), parenchymal thickness >=
      8 mm (P = 0.018), not performing portal vein/superior mesenteric vein resection
      (P = 0.004), and amylase level of drainage fluid on postoperative day 3 >= 375
      IU/L (P < 0.001). Pancreatic configuration data including MPDd and parenchymal
      thickness were good indicators of clinically relevant POPF.

PMID- 23975029
TI  - The nonenzymatic reactivity of the acyl-linked metabolites of mefenamic acid
      toward amino and thiol functional group bionucleophiles.
AB  - Mefenamic acid (MFA), a carboxylic acid-containing nonsteroidal anti-inflammatory
      drug, is metabolized into the chemically-reactive MFA-1-O-acyl-glucuronide (MFA-1
      O-G), MFA-acyl-adenylate (MFA-AMP), and the MFA-S-acyl-coenzyme A (MFA-CoA), all
      of which are electrophilic and capable of acylating nucleophilic sites on
      biomolecules. In this study, we investigate the nonenzymatic ability of each MFA
      acyl-linked metabolite to transacylate amino and thiol functional groups on the
      acceptor biomolecules Gly, Tau, l-glutathione (GSH), and N-acetylcysteine (NAC).
      In vitro incubations with each of the MFA acyl-linked metabolites (1 MUM) in
      buffer under physiologic conditions with Gly, Tau, GSH, or NAC (10 mM) revealed
      that MFA-CoA was 11.5- and 19.5-fold more reactive than MFA-AMP toward the
      acylation of cysteine-sulfhydryl groups of GSH and NAC, respectively. However,
      MFA-AMP was more reactive toward both Gly and Tau, 17.5-fold more reactive toward
      the N-acyl-amidation of taurine than its corresponding CoA thioester, while MFA
      CoA displayed little reactivity toward glycine. Additionally, mefenamic acid-S
      acyl-glutathione (MFA-GSH) was 5.6- and 108-fold more reactive toward NAC than
      MFA-CoA and MFA-AMP, respectively. In comparison with MFA-AMP and MFA-CoA, MFA-1
      O-G was not significantly reactive toward all four bionucleophiles. MFA-AMP, MFA
      CoA, MFA-1-O-G, MFA-GSH, and mefenamic acid-taurine were also detected in rat in
      vitro hepatocyte MFA (100 MUM) incubations, while mefenamic acid-glycine was not.
      These results demonstrate that MFA-AMP selectively reacts with the amino
      functional groups of glycine and lysine nonenzymatically, MFA-CoA selectively
      reacts nonenzymatically with the thiol functional groups of GSH and NAC, and MFA
      GSH reacts with the thiol functional group of GSH nonenzymatically, all of which
      may potentially elicit an idiosyncratic toxicity in vivo. 

PMID- 23975031
TI  - How long is antibiotic therapy necessary after urgent cholecystectomy for acute
      cholecystitis?
AB  - OBJECTIVE: The objective of the study was to analyze surgical site infection
      (SSI) frequency with different duration antibiotic courses to establish the
      minimum necessary duration. METHODS: This is an observational study of
      prospective surveillance of 287 consecutive patients (mean age 67.8 years)
      operated on for acute cholecystitis of grade II severity in the first 72 h.
      Postoperative antibiotics had been withdrawn before diagnosis of any infection as
      an inclusion criterion. Patients were classified into three groups, according to
      therapy duration: group 1 (0-4 days, n = 45, 15.7 %); group 2 (5-7 days, n = 75,
      26.1 %); and group 3 (>7 days, n = 167, 58.2 %). A multivariable analysis of risk
      infection was performed. RESULTS: Overall SSI frequency in groups 1, 2, and 3 was
      2.2, 10.7, and 9 %, respectively. Risk analysis showed an increase in both crude
      and adjusted relative risks of overall infection in group 2 (crude relative risk
      (RR): 4.80 (0.62-37.13); adjusted RR, 2.03 (0.20-20.91)) and in group 3 (crude
      RR, 4.04 (0.55-29.79); adjusted RR, 2.35 (0.28-20.05)) by comparison with group
      1, although without statistical significance. As a result, treatment lasting 4
      days or less was not associated with overall surgical site infection incidence
      higher than longer treatment. CONCLUSION: Antibiotic treatment over 4 days after
      early cholecystectomy provides no advantage in decreasing surgical site infection
      incidence.

PMID- 23975032
TI  - Studying the human immunome: the complexity of comprehensive leukocyte
      immunophenotyping.
AB  - A comprehensive study of the cellular components of the immune system requires
      both deep and broad immunophenotyping of numerous cell populations in an
      efficient and practical manner. In this chapter, we describe the technical
      aspects of studying the human immunome using high-dimensional (15 color)
      fluorescence-based immunophenotyping. We focus on the technical aspects of
      polychromatic flow cytometry and the initial stages in developing a panel for
      comprehensive leukocyte immunophenotyping (CLIP). We also briefly discuss how
      this panel is being used and the challenges of encyclopedic analysis of these
      rich data sets. 

PMID- 23975033
TI  - Emodin elicits cytotoxicity in human lung adenocarcinoma A549 cells through
      inducing apoptosis.
AB  - This study investigated the mechanism of the cytotoxic effect of emodin, an
      active anthraquinone, on human lung adenocarcinoma A549 cells. In vitro growth
      inhibition and suppression on colony forming were used to evaluate the effects of
      emodin on A549 cells. Emodin's ability in changing the expressions of apoptosis
      related genes was studied by real-time RT-PCR. Emodin could significantly inhibit
      the growth of A549 cells with IC50 = 16.85 MUg/ml (~60 MUM). It also
      concentration dependently inhibited the colony-forming ability of A549 cells with
      IC50 = 7.60 MUg/ml (~30 MUM). Hallmarks of apoptosis, such as single-strand DNA
      breakage and DNA fragmentation, were observed in A549 cells treated with emodin.
      Emodin (72 h) treatment could up-regulate the gene expression of FASL (p < 0.05)
      and down-regulate the gene expression of C-MYC (p < 0.01), but induce no
      significant changes in the gene expressions of MCL1, GAPDH, BAX and CCND1. These
      results suggest that emodin could induce growth inhibition and apoptosis in A549
      cells through modifying the extrinsic apoptotic pathways and the induction of
      cell cycle arrest.

PMID- 23975034
TI  - Methylphenidate and impulsivity: a comparison of effects of methylphenidate
      enantiomers on delay discounting in rats.
AB  - RATIONALE: Current formulations of methylphenidate (MPH) used in treatment of
      attention-deficit/hyperactivity disorder (ADHD) result in significantly different
      bioavailability of MPH enantiomers. Daytrana(r), a dl-MPH transdermal patch
      system, produces higher levels of l-MPH than when dl-MPH is administered orally
      (e.g., Ritalin(r)). One potential limitation of increased l-MPH was indicated in
      a preclinical study showing l-MPH may attenuate effects of d-MPH. OBJECTIVES: The
      objective of the study was to investigate the interactive effects of MPH
      enantiomers by (1) assessing drug effects via a preclinical model of
      "impulsivity" and (2) performing a quantitative dose equivalence analysis of MPH
      enantiomer interactions. METHODS: Sprague-Dawley rats were trained to emit either
      of two responses, one producing an immediate food pellet, the other producing
      four pellets delivered at increasing delays (0, 8, and 32 s). The percent
      selection of the larger food amount was graphed as a function of delay with the
      area under the curve (AUC) assessed. Increases in AUC are consistent with
      decreases in "impulsivity" (i.e., selection of the smaller, immediate over the
      larger, delayed reinforcer). RESULTS: Systemic administration of dl-MPH and d-MPH
      dose-dependently increased AUC, while l-MPH, morphine, and pentobarbital did not
      alter AUC. An analysis based upon dose equivalence indicated that dl-MPH produced
      additive effects that were not different from that predicted from effects of the
      enantiomers administered alone. CONCLUSIONS: The present results indicate
      pharmacologically selective effects in that only drugs prescribed for the
      treatment of ADHD symptoms decreased a measure of "impulsivity" and that l-MPH
      likely does not attenuate or enhance the effects of d-MPH in the current delay
      discounting task.

PMID- 23975035
TI  - Single dose of H3 receptor antagonist--ciproxifan--abolishes negative effects of
      chronic stress on cognitive processes in rats.
AB  - RATIONALE: The role of histamine neurons in stress evoked cognitive impairments
      remains unclear. Previous research has indicated that the blockade of H(3)-type
      histamine receptors may improve attention and memory in naive rodents.
      OBJECTIVES: The purpose of this study was to determine if ciproxifan,
      (cyclopropyl-(4-(3-1H-imidazol-4-yl) propyloxy) phenyl) ketone, an H(3) receptor
      antagonist, could alleviate cognitive deficits observed in chronically stressed
      rats. METHODS: Specifically, we attempted to characterize the preventive action
      of single dose of ciproxifan (3 mg/kg, i.p.) against an impairment caused by
      chronic restraint stress (2 h daily for 21 days) on recognition memory tested in
      an object recognition task and on the long-term memory tested in a passive
      avoidance test. RESULTS: We found that administration of ciproxifan potently
      prevented deleterious effects of chronic restraint stress, when administered
      prior to learning, or immediately after learning, or before retrieval on both the
      recognition (p<0.001) and the passive avoidance behavior (p<0.001). CONCLUSIONS:
      These data support the idea that modulation of H(3) receptors represents a novel
      and viable therapeutic strategy in the treatment of stress evoked cognitive
      impairments.

PMID- 23974980
TI  - Recent advances in 2D and 3D in vitro systems using primary hepatocytes,
      alternative hepatocyte sources and non-parenchymal liver cells and their use in
      investigating mechanisms of hepatotoxicity, cell signaling and ADME.
AB  - This review encompasses the most important advances in liver functions and
      hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a
      complex architecture of nested, zonated lobules, the liver consists of
      approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being
      involved in a secondary phase that may dramatically aggravate the initial damage.
      Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear
      receptors (including PXR, CAR, HNF-4alpha, FXR, LXR, SHP, VDR and PPAR) and
      signaling pathways. When isolating liver cells, some pathways are activated,
      e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4alpha),
      resulting in up- and downregulation of hundreds of genes. An understanding of
      these changes is crucial for a correct interpretation of in vitro data. The
      possibilities and limitations of the most useful liver in vitro systems are
      summarized, including three-dimensional culture techniques, co-cultures with non
      parenchymal cells, hepatospheres, precision cut liver slices and the isolated
      perfused liver. Also discussed is how closely hepatoma, stem cell and iPS cell
      derived hepatocyte-like-cells resemble real hepatocytes. Finally, a summary is
      given of the state of the art of liver in vitro and mathematical modeling systems
      that are currently used in the pharmaceutical industry with an emphasis on drug
      metabolism, prediction of clearance, drug interaction, transporter studies and
      hepatotoxicity. One key message is that despite our enthusiasm for in vitro
      systems, we must never lose sight of the in vivo situation. Although hepatocytes
      have been isolated for decades, the hunt for relevant alternative systems has
      only just begun.

PMID- 23975036
TI  - Lapses of attention as outcome measure of the on-the-road driving test.
AB  - BACKGROUND: Lapses are brief periods of inattention and reduced alertness which
      may be a risk factor for car crashes. The Dutch on-the-road driving test is
      applied to examine effects of CNS drugs on driving, using the standard deviation
      of lateral position (SDLP) as primary outcome measure. This paper examines the
      utility of an alternative outcome measure, lapses, to determine the degree to
      which CNS drugs impair driving. METHODS: Data from two double-blind, placebo
      controlled on-the-road driving studies that examined the residual effects of
      hypnotic drugs were reanalyzed. The treatments were zaleplon and zolpidem tested
      4 h after middle-of-the-night administration, and ramelteon and zopiclone tested
      8.5 h after bedtime administration. In addition to SDLP, outcome measures related
      to lapses (number, total duration, and maximum deviation) were computed. A lapse
      was defined as a continuous change in lateral position of greater than 100 cm,
      lasting for at least 4 s. RESULTS: Both SDLP and lapses were able to detect
      significant driving impairment after middle-of-the-night administration of
      zolpidem (10 and 20 mg) and bedtime administration of ramelteon (8 mg) and
      zopiclone (7.5 mg) relative to placebo. Both measures found no differences from
      placebo after middle-of-the-night administration of zaleplon (10 and 20 mg). The
      number of lapses was more sensitive in differentiating treatment from placebo
      than the maximum deviation of a lapse or their duration. After considering
      different lapse duration criteria, a lapse was redefined as a continuous change
      in lateral position of greater than 100 cm, lasting for at least 8 s. This change
      in definition did not significantly alter the outcome of the statistical
      analyses. CONCLUSIONS: In addition to SDLP, the number of lapses is a useful
      outcome measure to identify treatments that impair driving. Future research
      should determine the unique contributions of SDLP and lapses in defining the
      potential risk of CNS drugs on driving.

PMID- 23975037
TI  - Lasting neurobehavioral abnormalities in rats after neonatal activation of
      serotonin 1A and 1B receptors: possible mechanisms for serotonin dysfunction in
      autistic spectrum disorders.
AB  - RATIONALE: Perinatal exposure of rats to selective serotonin reuptake inhibitors
      (SSRIs) produces sensory and social abnormalities paralleling those seen in
      autistic spectrum disorders (ASDs). However, the possible mechanism(s) by which
      this exposure produces behavioral abnormalities is unclear. OBJECTIVE: We
      hypothesized that the lasting effects of neonatal SSRI exposure are a consequence
      of abnormal stimulation of 5-HT1A and/or 5-HT1B receptors during brain
      development. We examined whether such stimulation would result in lasting sensory
      and social deficits in rats in a manner similar to SSRIs using both direct
      agonist stimulation of receptors as well as selective antagonism of these
      receptors during SSRI exposure. METHODS: Male and female rat pups were treated
      from postnatal days 8 to 21. In Experiment 1, pups received citalopram (20
      mg/kg/day), saline, (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide (8-OH
      DPAT; 0.5 mg/kg/day) or 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2
      a]-quinoxaline dimaleate (CGS-12066B; 10 mg/kg/day). In Experiment 2, a separate
      cohort of pups received citalopram (20 mg/kg/day), or saline which was combined
      with either N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclo
      hexanecarboxamide maleate (WAY-100635; 0.6 mg/kg/day) or N-[4-methoxy-3-(4-methyl
      1-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-1-1'-biphenyl
      4-carboxamide (GR-127935; 6 mg/kg/day) or vehicle. Rats were then tested in
      paradigms designed to assess sensory and social response behaviors at different
      time points during development. RESULTS: Direct and indirect neonatal stimulation
      of 5-HT1A or 5-HT1B receptors disrupts sensory processing, produces neophobia,
      increases stereotypic activity, and impairs social interactions in manner
      analogous to that observed in ASD. CONCLUSION: Increased stimulation of 5-HT1A
      and 5-HT1B receptors plays a significant role in the production of lasting social
      and sensory deficits in adult animals exposed as neonates to SSRIs.

PMID- 23975038
TI  - Reduction of excessive alcohol drinking by a novel GABAB receptor positive
      allosteric modulator ADX71441 in mice.
AB  - RATIONALE: A promising pharmacotherapy for alcohol use disorders has been
      positive allosteric modulators (PAMs) of the gamma-aminobutyric acid receptor B
      (GABAB R) since GABAB R PAMs reduce ethanol drinking and self-administration in
      rodents. OBJECTIVE: The current studies investigated a novel, selective GABAB R
      PAM, ADX71441, in comparison to naltrexone in a protocol of ethanol binge-like
      drinking, drinking-in-the-dark (DID), and in a model of long-term, excessive
      drinking, intermittent access to ethanol (IA). METHODS: Male C57BL/6 J mice were
      given doses of ADX71441 (3, 10, 30 mg/kg, p.o.) before the fourth test day of
      repeated DID access to 20 % ethanol. Another group of mice had a history of 4
      weeks of IA before ADX71441 (3, 10, 17 mg/kg, p.o.) treatment. The opioid
      antagonist, naltrexone (0.1, 1, 10 mg/kg, i.p.), was administered to different
      groups of mice in both protocols as a positive control. RESULTS: In both DID and
      IA protocols, ADX71441 showed a selective and potent reduction of ethanol
      drinking, but not water drinking, while naltrexone had a more modest and
      transient effect on reducing ethanol drinking. The long-lasting effect of
      ADX71441 agrees with its plasma pharmacokinetics in showing peak concentrations
      at 2 h followed by a slow decay lasting well beyond 8 h. CONCLUSIONS: These
      findings support previous studies demonstrating that GABAB R PAMs decrease
      voluntary ethanol intake without altering water intake. ADX71441 may be a
      worthwhile candidate for developing a treatment of alcoholism, yet its site of
      action in the brain and long-term pharmacological effects require further
      exploration.

PMID- 23975039
TI  - The antidepressant-like effects of topiramate alone or combined with 17beta
      estradiol in ovariectomized Wistar rats submitted to the forced swimming test.
AB  - RATIONALE: There is a significant delay in the clinical response of
      antidepressant drugs, and antidepressant treatments produce side effects.
      OBJECTIVE: We examined the relationship between 17beta-estradiol and topiramate
      in ovariectomized Wistar rats submitted to the forced swimming test (FST).
      METHODS: Topiramate was administered alone or combined with 17beta-estradiol to
      ovariectomized rats submitted to the FST. RESULTS: Topiramate (20 mg/kg, P <
      0.05; 30 mg/kg, P < 0.05) reduced immobility by increasing swimming; these
      effects were antagonized by finasteride (50 mg/kg). In interaction experiments,
      topiramate (10 mg/kg) plus 17beta-estradiol (5 micrograms per rat; P < 0.05)
      reduced immobility by increasing swimming behavior. Besides, 17beta-estradiol
      (2.5 micrograms per rat) shortened the onset of the antidepressant-like effects
      of topiramate (P < 0.05). In the open field test, topiramate alone or combined
      with 17beta-estradiol (P < 0.05) reduced locomotion. CONCLUSIONS: Topiramate
      alone or combined with 17beta-estradiol produced antidepressant-like actions; and
      17beta-estradiol shortened the onset of the antidepressant-like effects of
      topiramate.

PMID- 23975041
TI  - Nanostructured hydroxyapatite/poly(lactic-co-glycolic acid) composite coating for
      controlling magnesium degradation in simulated body fluid.
AB  - Biodegradable magnesium (Mg) and its alloys have many attractive properties (e.g.
      comparable mechanical properties to cortical bone) for orthopedic implant
      applications, but they degrade too rapidly in the human body to meet clinical
      requirements. Nanostructured hydroxyapatite (nHA)/poly(lactic-co-glycolic acid)
      (PLGA) composite coatings provide synergistic properties for controlling
      degradation of Mg-based substrates and improving bone-implant integration. In
      this study, nHA/PLGA composites were spin coated onto Mg-based substrates and the
      results showed that the nHA/PLGA coatings retained nano-scale features with nHA
      dispersed in PLGA matrix. In comparison with non-coated Mg, the nHA/PLGA
      composite coated Mg increased the corrosion potential and decreased the corrosion
      current in revised simulated body fluid (rSBF). After 24 h of immersion in rSBF,
      increased calcium phosphate (CaP) deposition and formation of Mg-substituted CaP
      rosettes were observed on the surface of the nHA/PLGA coated Mg, indicating
      greater bioactivity. In contrast, no significant CaP was deposited on the PLGA
      coated Mg. Since both PLGA coating and nHA/PLGA coating showed some degree of
      delamination from Mg-based substrates during extended immersion in rSBF, the
      coating processing and properties should be further optimized in order to take
      full advantage of biodegradable Mg and nHA/PLGA nanocomposites for orthopedic
      applications. 

PMID- 23975040
TI  - The Rag2-Il2rb-Dmd- mouse: a novel dystrophic and immunodeficient model to assess
      innovating therapeutic strategies for muscular dystrophies.
AB  - The development of innovative therapeutic strategies for muscular dystrophies,
      particularly cell-based approaches, is still a developing field. Although
      positive results have been obtained in animal models, they have rarely been
      confirmed in patients and resulted in very limited clinical improvements,
      suggesting some specificity in humans. These findings emphasized the need for an
      appropriate animal model (i.e., immunodeficient and dystrophic) to investigate in
      vivo the behavior of transplanted human myogenic stem cells. We report a new
      model, the Rag2(-)Il2rb(-)Dmd(-) mouse, which lacks T, B, and NK cells, and also
      carries a mutant Dmd allele that prevents the production of any dystrophin
      isoform. The dystrophic features of this new model are comparable with those of
      the classically used mdx mouse, but with the total absence of any revertant
      dystrophin positive fiber. We show that Rag2(-)Il2rb(-)Dmd(-) mice allow long
      term xenografts of human myogenic cells. Altogether, our findings indicate that
      the Rag2(-)Il2rb(-)Dmd(-) mouse represents an ideal model to gain further
      insights into the behavior of human myogenic stem cells in a dystrophic context,
      and can be used to assess innovative therapeutic strategies for muscular
      dystrophies.

PMID- 23975042
TI  - Patterns of recurrence in patients treated with bevacizumab in the primary
      treatment of advanced epithelial ovarian cancer.
AB  - OBJECTIVE: The purpose of this study was to compare the distribution of the first
      site of recurrence in patients with epithelial ovarian cancer (EOC) who received
      first-line treatment with bevacizumab compared with patients who did not receive
      bevacizumab. METHODS: From the Cancer Registry database at our institutions, we
      identified a group of patients with recurrent EOC who underwent treatment from
      January 1, 2005, to December 31, 2010. Each patient record was evaluated to
      classify the site of first recurrence. Correlation between categorical variables
      was assessed with chi2 test. RESULTS: Two hundred ninety-two patients with
      advanced EOC (stage III or IV) who originally responded to chemotherapy and had a
      recurrence were identified. Of these, 37 (12.5%) had received postoperative
      chemotherapy bevacizumab, and 255 (87.5%) did not. Compared with those not
      treated with bevacizumab, there was a lower incidence of liver recurrence (0% vs
      9%; P = 0.05) and a higher rate of lung and/or pleural recurrence (22% vs 5%; P =
      0.001) and recurrence at distant sites (22% vs 9%; P = 0.03) in patients who
      received bevacizumab. There was no difference in the incidence of ascites at the
      time of recurrence between these groups. CONCLUSIONS: Patients who received
      bevacizumab as part of primary treatment for EOC had a higher rate of lung and/or
      pleural recurrence and a lower rate of liver recurrence. There was no difference
      in the rate of ascites at the time of recurrence.

PMID- 23975044
TI  - Editor's note.

PMID- 23975045
TI  - The sonographic stenosis index: computer simulation of a novel method for
      detecting and quantifying arterial narrowing.
AB  - PURPOSE: We introduce a new technique for quantifying arterial stenoses, stenosis
      index (SI), using frequency analysis of the spectral Doppler waveform. METHODS:
      Spectral Doppler waveforms obtained distal to arterial stenoses were enveloped,
      and the envelope was transformed into the frequency domain via Fourier transform.
      Stenosis index represents the ratio of the power in high-frequency harmonics to
      the power in the fundamental frequency.Stenosis index was compared with resistive
      index (RI), pulsatility index (PI), and acceleration time using 1000 computer
      simulations of waveforms from arteries distal to transplanted renal artery
      stenoses using Kendall tau correlation coefficients and receiver operating
      characteristic curve analyses. RESULTS: The mean r's using Kendall tau
      correlation for SI, RI, and PI were 0.58, 0.31, and 0.45, respectively. The 95%
      confidence intervals for increase in r's for SI versus RI and PI to the degree of
      stenosis (none, mild, and severe) in the 1000 computer simulations were 0.22 to
      0.34 and 0.07 to 0.19. The difference between the areas under the curves for SI
      versus RI and PI for normal artery versus mild stenosis was 0.26 to 0.44 and
      0.078 to 0.24. Stenosis index and acceleration time were not significantly
      different. CONCLUSIONS: In computational models, SI outperformed RI and PI in
      correlation and receiver operating characteristic curve analysis. Further testing
      of SI is warranted.

PMID- 23975043
TI  - Inflammation, heart disease, and depression.
AB  - Morbidity and mortality of cardiovascular disease is exceedingly high worldwide.
      Depressive illness afflicts a significant portion of the population worldwide.
      Epidemiological studies have confirmed the high co-morbidity between these two
      entities and the co-morbidity is bidirectional. Systems that contribute to this
      co-morbidity include the central and autonomic nervous systems, the
      neuroendocrine, immune, vascular and hematologic systems. Specific
      pathophysiologic factors include imbalance between the sympathetic and the
      parasympathetic systems, sympathoadrenal activation, hypothalamic-pituitary
      adrenal axis activation, immune system dysregulation with release of pro
      inflammatory cytokines and chemokines, platelet activation and hypercoaguability.
      Inflammation occurs in cardiac and cardiovascular pathology independent of the
      presence or absence of depression and in depression. Inflammation is closely
      associated with endothelial dysfunction which is a preamble to atherosclerosis
      and atherothrombosis. A likely common instigator underlying this co-morbidity is
      mental stress leading to sustained sympathetic overdrive and diminished vagal
      tone. Diminished vagal tone contributes to a pro-inflammatory status which
      affects neurotransmitter regulation, specifically serotonergic transmission.
      Stress hormones and certain pro-inflammatory substances released by macrophages
      and microglia upregulate the rate-limiting enzymes in the metabolic pathway of
      tryptophan. This results in a shunt in tryprophan metabolism away from serotonin
      formation and down the kynurenine pathway with resulting formation of neurotoxic
      metabolites. 

PMID- 23975046
TI  - The elusive parathyroid adenoma: techniques for detection.
AB  - The success of minimally invasive surgery for hyperparathyroidism depends on
      accurate preoperative localization of the hyperfunctioning adenoma with imaging.
      Ultrasound is an excellent initial modality because it has a high positive
      predictive value, sensitivity, and specificity, while being inexpensive and
      noninvasive without use of ionizing radiation. Determining the exact location and
      number of adenomas is essential, because these factors guide the surgical
      approach. The goal of this review article was to discuss specific sonographic
      techniques that can be applied to find even the elusive adenoma, which include
      (1) compression scanning, (2) color Doppler, (3) scanning regions where ectopic
      glands may be located, and (4) evaluating intrathyroidal adenomas. 

PMID- 23975047
TI  - Lung cancer metastatic to breast: case report and review of the literature.
AB  - The incidence of metastases to the breast from nonbreast carcinoma is less than
      1% of all breast cancers; of these, adenocarcinoma of the lung to breast is a
      small proportion (<0.1% of breast carcinomas). The imaging findings of a case of
      metastatic lung adenocarcinoma to the breast are presented with a review of the
      literature. Imaging findings including elastography suggesting the breast mass is
      not a primary breast cancer are highlighted. The importance of notifying the
      pathologist that nonbreast metastatic disease is in the differential is
      discussed. The use of appropriate tumor markers is needed; otherwise, the lesion
      may be interpreted as a triple negative breast cancer. 

PMID- 23975048
TI  - Twin pregnancy with complete hydatidiform mole and normal coexisting fetus.

PMID- 23975049
TI  - Ultrasound-guided skeletal biopsy: a case report.

PMID- 23975050
TI  - Colonic atresia.

PMID- 23975051
TI  - The expected and unexpected: incidental discovery of an ovarian mass with acute
      appendicitis.

PMID- 23975052
TI  - [Joint-preserving osteotomy of malunited ankle and pilon fractures].
AB  - Malunion and nonunion after ankle and pilon fractures regularly lead to the
      development of painful functional impairment even in cases of only mild axial
      deviation or residual joint incongruity. Involvement of the tibial pilon results
      in rapid progression of posttraumatic ankle arthritis. Corrective osteotomy with
      joint preservation aims at secondary anatomical reconstruction with functional
      rehabilitation. This requires a careful preoperative analysis and will be
      possible in carefully selected cases only. Prerequisites for successful
      reconstruction are intact cartilage, sufficient bone quality, residual joint
      function and good patient compliance. Since the works of B. G. Weber, joint
      sparing osteotomy is an established treatment option for malunited malleolar
      fractures with reliable long-term results and low rates of complications and
      secondary fusions. Key to success is the re-establishment of the length of the
      distal fibula and repositioning into the tibial incisura in cases of syndesmotic
      instability. Corrections of the medial malleolus and posterior tibial fragment
      are less frequent. Corrective intra-articular osteotomies for malunited pilon
      fractures are rarely feasible because of manifest arthritis at the time of
      patient presentation in most cases. Besides case reports there is only one series
      of 14 patients available in the literature. At 5-year follow-up, a good to
      excellent result was seen in 10 cases and secondary ankle fusion was done in 2
      patients with a poor result. Anatomical reconstruction of malunited tibial pilon
      fractures appears to be a viable treatment option besides arthroplasty and fusion
      in carefully selected patients.

PMID- 23975053
TI  - Correlation of botulinum toxin dose with neurophysiological parameters of
      efficacy and safety in the glabellar muscles: a double-blind, placebo-controlled,
      randomized study.
AB  - Despite the extensive use of botulinum toxin type A (BoNT-A) in treatments for
      glabellar frown lines, the dose-response effect in the glabellar muscles remains
      unknown. The aim of this randomized, double-blind, placebo-controlled prospective
      study was to characterize the neurophysiological parameters that correlate with
      the effect of BoNT-A in the glabellar muscles and its diffusion to surrounding
      ocular muscles. Sixteen healthy women were recruited and randomized to 3
      different dose-groups of onabotulinumtoxin A (Vistabel(r)) or placebo and
      followed 24 weeks by neuro-physiological examinations. Efficacy of treatment on
      corrugator supercilii muscles was measured by compound motor action potential
      (CMAP) and electromyography (EMG). Photographs were used to score glabellar frown
      lines. Diffusion of the drug to surrounding muscles was assessed by CMAP of the
      nasalis muscle, EMG and concentric needle electrode jitter analysis (CNE) of the
      orbicularis oculi muscle. CMAP reduction correlated well with intramuscular BoNT
      A dose. Muscle paralysis, measured by EMG, began from 2 weeks and was not
      entirely reversed at 24 weeks in individuals who received high dose of
      onabotulinumtoxin. Limited diffusion of orbicularis oculi was detected with CNE.
      In conclusion, we developed a novel neurophysiological strategy for effect
      evaluation of BoNT-A in glabellar muscles. CMAP and EMG correlated with given
      BoNT-A dose and are more defined effect measures than clinical glabellar photo
      scales. 

PMID- 23975054
TI  - Anatomic distribution of cancers and colorectal adenomas according to age and sex
      and relationship between proximal and distal neoplasms in an i-FOBT-positive
      average-risk Italian screening cohort.
AB  - BACKGROUND AND AIMS: Subsite-specific incidence rates of colorectal cancer (CRC)
      and adenomas may vary considerably by race, sex and age as well as due to
      different screening strategies. We assessed variations in the anatomical
      distribution of adenomas according to age and sex in an average-risk screening
      cohort testing positive at immunological faecal occult blood test (i-FOBT) in
      northern Italy. METHODS: Data from 2,281 consecutive asymptomatic i-FOBT-positive
      subjects ageing 50-70 years undergone colonoscopy were reviewed. Size, number,
      macroscopic and histological features of all adenomas found as well as their
      proximal or distal location in relation to the splenic flexure were examined.
      Odds ratios (OR) of proximal neoplasms, according to the presence of distal
      neoplasms and other selected covariates were assessed by multiple logistic
      regression analysis. RESULTS: A total of 2,599 neoplasms were found in 1,396
      patients. Of these, 116 (5 %) were colorectal cancers, diagnosed in 106 patients.
      Out of 2,483 adenomas found, 1,564 (63 %) were sessile, 795 (32 %) were
      peduncolated and 124 (5 %) were flat-type; 54 % of all adenomas were tubular, 36
      % were tubulovillous or villous, and 10 % were serrated adenomas. The majority of
      neoplasms (66 %) were located in the distal colon. Tumour subsite distribution
      was consistent in both sexes, whereas significant proximal migration of neoplasms
      occurred in the older age cohort. Indeed, the rate of proximal neoplasms in
      patients aged >=60 years was 37 % as compared with 29 % in those ageing 50-59
      years. Male gender (OR 1.84), age of 60 years or older (OR 1.44), having a family
      history of colorectal neoplasms (OR 1.47) and presence of at least 1 distal
      advanced adenoma (OR 1.63) were all significant predictors of advanced proximal
      neoplasms. CONCLUSIONS: A left to right shift of colorectal adenomas with
      increasing age is evident in northern Italian asymptomatic i-FOBT-positive
      population. Advanced proximal neoplasms are not uncommon in subjects with or
      without distal adenomas, especially after 60 years of age. This should be
      carefully considered when implementing public screening strategies for CRC since
      the use of flexible sigmoidoscopy as a screening tool, particularly in older age
      groups, appears to be less effective.

PMID- 23975055
TI  - The influence of desmocollin 1-3 expression on prognosis after curative resection
      of colorectal liver metastases.
AB  - PURPOSE: Prognosis after curative resection of colorectal liver metastases is
      hard to determine based on clinical parameters; biomarkers are therefore needed.
      The purpose of this study was to determine the value of desmocollins (DSC) as
      potential biomarkers. Desmocollins are responsible for cell-cell adhesion in
      epithelial tissue; their loss may lead to reduced cellular adhesion and
      facilitate cellular migration, enabling tumor cells to form distant metastases.
      We analyzed DSC expression in colorectal liver metastases with respect to the
      risk of recurrence following liver resection. METHODS: Tissue microarrays from
      257 consecutive patients who underwent R0-resection of colorectal liver
      metastases were constructed. RESULTS: Low expression of DSC 1, 2, and 3 was
      observed in 55, 54, and 79 % of liver metastases. There was no correlation
      between site or stage of the primary tumor, presence of extrahepatic tumor,
      grading, size or number of metastases, and desmocollin expression. Primary tumor
      stage I or II (p = 0.005) and no or few lymph node metastases (p < 0.001) were
      associated with a significantly better disease-free survival on univariate
      analysis. These parameters reached only marginal significance on multivariate
      analysis (p = 0.059 and p = 0.052, respectively), as did desmocollin 3 expression
      (p = 0.050). In the subgroup of patients with stages III-IV primary tumors,
      however, multivariate analysis showed a significant correlation between DSC 3
      expression and disease-free survival after liver resection (p = 0.009).
      CONCLUSIONS: Reduced expression of DSC3 correlated with an increased risk of
      developing tumor recurrence after resection of liver metastases. These findings
      may be helpful in selecting high-risk patients who might benefit from multimodal
      therapy.

PMID- 23975056
TI  - Reversible redox reactions in an epitaxially stabilized SrCoO(x) oxygen sponge.
AB  - Fast, reversible redox reactions in solids at low temperatures without
      thermomechanical degradation are a promising strategy for enhancing the overall
      performance and lifetime of many energy materials and devices. However, the
      robust nature of the cation's oxidation state and the high thermodynamic barrier
      have hindered the realization of fast catalysis and bulk diffusion at low
      temperatures. Here, we report a significant lowering of the redox temperature by
      epitaxial stabilization of strontium cobaltites (SrCoO(x)) grown directly as one
      of two distinct crystalline phases, either the perovskite SrCoO(3-delta) or the
      brownmillerite SrCoO(2.5). Importantly, these two phases can be reversibly
      switched at a remarkably reduced temperature (200-300  degrees C) in a
      considerably short time (< 1 min) without destroying the parent framework. The
      fast, low-temperature redox activity in SrCoO(3-delta) is attributed to a small
      Gibbs free-energy difference between two topotatic phases. Our findings thus
      provide useful information for developing highly sensitive electrochemical
      sensors and low-temperature cathode materials.

PMID- 23975057
TI  - Suppression of thermal conductivity by rattling modes in thermoelectric sodium
      cobaltate.
AB  - The need for both high electrical conductivity and low thermal conductivity
      creates a design conflict for thermoelectric systems, leading to the
      consideration of materials with complicated crystal structures. Rattling of ions
      in cages results in low thermal conductivity, but understanding the mechanism
      through studies of the phonon dispersion using momentum-resolved spectroscopy is
      made difficult by the complexity of the unit cells. We have performed inelastic X
      ray and neutron scattering experiments that are in remarkable agreement with our
      first-principles density-functional calculations of the phonon dispersion for
      thermoelectric Na(0.8)CoO2, which has a large-period superstructure. We have
      directly observed an Einstein-like rattling mode at low energy, involving large
      anharmonic displacements of the sodium ions inside multi-vacancy clusters. These
      rattling modes suppress the thermal conductivity by a factor of six compared with
      vacancy-free NaCoO2. Our results will guide the design of the next generation of
      materials for applications in solid-state refrigerators and power recovery.

PMID- 23975058
TI  - Spontaneous evolution of bicontinuous nanostructures in dealloyed Li-based
      systems.
AB  - Dealloying, the selective dissolution of one or more of the elemental components
      of an alloy, is an important corrosion mechanism and a technologically relevant
      process used to fabricate nanoporous metals for a variety of applications
      including catalysis, sensing, actuation, supercapacitors and radiation-damage
      resistant materials. In noble-metal alloy systems for which the ambient
      temperature solid-state diffusivity is minuscule, dealloying occurs at a
      composition-dependent critical potential above which bicontinuous nanoporous
      structures evolve and below which a full-coverage layer of the more-noble
      component forms causing the alloy surface to become passive. In contrast, for
      alloy systems exhibiting significant solid-state diffusive transport, our
      understanding of dealloying-induced morphologies and the electrochemical
      parameters controlling this are largely unexplored. Here, we examine dealloying
      of Li from Li-Sn alloys and show that depending on alloy composition, particle
      size and dealloying rate, all known dealloyed morphologies evolve including
      bicontinuous nanoporous structures and hollow core-shell particles. Furthermore,
      we elucidate the role of bulk diffusion in morphology evolution using
      chronopotentiometry and linear sweep voltammetry. Our results may have
      implications for lithium-ion battery development while significantly broadening
      the spectrum of strategies for obtaining new nanoporous materials through
      dealloying. 

PMID- 23975060
TI  - Reliability of clinician rated physical effort determination during functional
      capacity evaluation in patients with chronic musculoskeletal pain.
AB  - INTRODUCTION: Functional capacity evaluation (FCE) can be used to make clinical
      decisions regarding fitness-for-work. During FCE the evaluator attempts to assess
      the amount of physical effort of the patient. The aim of this study is to analyze
      the reliability of physical effort determination using observational criteria
      during FCE. METHODS: Twenty-one raters assessed physical effort in 18 video
      recorded FCE tests independently on two occasions, 10 months apart. Physical
      effort was rated on a categorical four-point physical effort determination scale
      (PED) based on the Isernhagen criteria, and a dichotomous submaximal effort
      determination scale (SED). Cohen's Kappa, squared weighted Kappa and % agreement
      were calculated. RESULTS: Kappa values for intra-rater reliability of PED and SED
      for all FCE tests were 0.49 and 0.68 respectively. Kappa values for inter-rater
      reliability of PED for all FCE tests in the first and the second session were
      0.51, and 0.72, and for SED Kappa values were 0.68 and 0.77 respectively. The
      inter-rater reliability of PED ranged from kappa = 0.02 to kappa = 0.99 between
      FCE tests. Acceptable reliability scores (kappa > 0.60, agreement >=80 %) for
      each FCE test were observed in 38 % of scores for PED and 67 % for SED. On
      average material handling tests had a higher reliability than postural tolerance
      and ambulatory tests. CONCLUSION: Dichotomous ratings of submaximal effort are
      more reliable than categorical criteria to determine physical effort in FCE
      tests. Regular education and training may improve the reliability of
      observational criteria for effort determination.

PMID- 23975059
TI  - Potential savings associated with drug substitution in Medicare Part D: the
      Translating Research into Action for Diabetes (TRIAD) study.
AB  - BACKGROUND: Drug substitution is a promising approach to reducing medication
      costs. OBJECTIVE: To calculate the potential savings in a Medicare Part D plan
      from generic or therapeutic substitution for commonly prescribed drugs. DESIGN:
      Cross-sectional, simulation analysis. PARTICIPANTS: Low-income subsidy (LIS)
      beneficiaries (n = 145,056) and non low-income subsidy (non-LIS) beneficiaries (n
      = 1,040,030) enrolled in a large, national Part D health insurer in 2007 and
      eligible for a possible substitution. MEASUREMENTS: Using administrative data
      from 2007, we identified claims filled for brand-name drugs for which a direct
      generic substitute was available. We also identified the 50 highest cost drugs
      separately for LIS and non-LIS beneficiaries, and reached consensus on which
      drugs had possible therapeutic substitutes (27 for LIS, 30 for non-LIS). For each
      possible substitution, we used average daily costs of the original and substitute
      drugs to calculate the potential out-of-pocket savings, health plan savings, and
      when applicable, savings for the government/LIS subsidy. RESULTS: Overall, 39 %
      of LIS beneficiaries and 51 % of non-LIS beneficiaries were eligible for a
      generic and/or therapeutic substitution. Generic substitutions resulted in an
      average annual savings of $160 in the case of LIS beneficiaries and $127 in the
      case of non-LIS beneficiaries. Therapeutic substitutions resulted in an average
      annual savings of $452 in the case of LIS beneficiaries and $389 in the case of
      non-LIS beneficiaries. CONCLUSIONS: Our findings indicate that drug substitution,
      particularly therapeutic substitution, could result in significant cost savings.
      There is a need for additional studies evaluating the acceptability of
      therapeutic substitution interventions within Medicare Part D.

PMID- 23975062
TI  - Swelling of submandibular region. Plunging ranula.

PMID- 23975061
TI  - Matrix metalloproteinase-3, vitamin D receptor gene polymorphisms, and
      occupational risk factors in lumbar disc degeneration.
AB  - BACKGROUND: Lumbar disc degeneration (LDD) is a process that begins early in
      life, contributing to the development of low back pain. LDD is a consequence of a
      variety of factors, and its etiology remains poorly understood. Objectives to
      investigate occupational and genetic risk factors inducing lumbar disc
      degeneration, and to evaluate the possible association of genetic polymorphisms
      of matrix metalloproteinase 3 (MMP-3) and vitamin D receptor (VDR) with the
      severity of LDD in an Egyptian population. SUBJECTS AND METHODS: A case control
      study involving 84 LDD and 60 controls was carried out. Five types of work
      related factors were investigated by questionnaire, complete neurological
      examination for all subjects and MRI for the cases. Polymerase chain reaction and
      restriction fragment length polymorphism methods were applied to detect
      polymorphisms in MMP-3 Promoter (-1,171 6A/5A) (rs 731236) and VDR-Apa (rs
      35068180). RESULTS: We found that family history, back injury, smoking, high
      level of sitting, bending/twisting, physical workload, lifting, whole body
      vibration, mutant allele 5A of MMP-3 and mutant allele T of VDR were
      significantly associated with LDD (OR = 2.9, 3.1, 2.1, 11.1, 15.9, 11.7, 8.2,
      12.6, 2.5 and 3.1 respectively, p < 0.05). Cases that carry allele 5A and/or
      allele T were associated with LDD severity. CONCLUSION: LDD is closely associated
      in occurrence and severity with occupational, environmental risk factors and
      susceptibility genes namely MMP-3, and VDR (ApaI). This study throws light on the
      importance of screening for early detection of susceptible individuals and
      disease prevention.

PMID- 23975063
TI  - Single-center experience in the endovascular management of isolated iliac artery
      aneurysm.
AB  - BACKGROUND: Isolated iliac artery aneurysms (IAA) are relatively uncommon and
      represent 2-7% of all intra-abdominal aneurysms. Surgery is the gold standard
      treatment for IAA. However, endovascular stent-graft placement is gaining
      acceptance as an alternative to surgery especially in patients with high surgical
      risk. PURPOSE: To evaluate the effectiveness and safety of endovascular
      management of isolated IAA having various anatomic and pathologic bases. MATERIAL
      AND METHODS: Between 2008 and 2011, 31 patients who underwent endovascular
      treatment for isolated IAA were retrospectively analyzed. The mean aneurysm size
      was 43 mm (range, 30-71 mm). The age ranged from 37 to 87 years (mean, 70.0
      years). Isolated IAAs were treated in one of three different ways: (i) infrarenal
      aortic stent-graft placement with limb extension; (ii) stent-graft placement for
      isolated iliac artery coverage; and (iii) embolization with a coil and a vascular
      plug combined with femoral-femoral bypass grafting. All patients were assessed by
      contrast-enhanced computed tomography (CT). The mean follow-up period was 25.1
      months (range, 1-60 months). RESULTS: Common iliac artery involvement was seen in
      28 patients. Ten (35.7%) of those patients also had an internal IAA. Three
      patients had an isolated internal IAA. Infrarenal stent-graft placement was
      performed in 25 patients. Stent-graft placement for coverage of the only iliac
      artery was performed in five patients. One patient, who had a mycotic aneurysm of
      the right common iliac artery underwent coil embolization of the ipsilateral
      common iliac artery with concurrent femoral-femoral bypass graft. Five of the 31
      patients (16.1%) with stent grafts had type II endoleaks at the time of the last
      imaging study, one of those patients underwent percutaneous embolization with
      glue. None of the patients showed major procedure-related complications.
      CONCLUSION: Percutaneous management of IAA is effective and safe with various
      techniques depending on the anatomical and pathologic features of the isolated
      IAA.

PMID- 23975064
TI  - Targeting single-walled carbon nanotubes for the treatment of breast cancer using
      photothermal therapy.
AB  - This paper focuses on the targeting of single-walled carbon nanotubes (SWNTs) for
      the treatment of breast cancer with minimal side effects using photothermal
      therapy. The human protein annexin V (AV) binds specifically to anionic
      phospholipids expressed externally on the surface of tumour cells and endothelial
      cells that line the tumour vasculature. A 2 h incubation of the SWNT-AV conjugate
      with proliferating endothelial cells followed by washing and near-infrared (NIR)
      irradiation at a wavelength of 980 nm was enough to induce significant cell
      death; there was no significant cell death with irradiation or the conjugate
      alone. Administration of the same conjugate i.v. in BALB/c female mice with
      implanted 4T1 murine mammary at a dose of 0.8 mg SWNT kg(-1) and followed one day
      later by NIR irradiation of the tumour at a wavelength of 980 nm led to complete
      disappearance of implanted 4T1 mouse mammary tumours for the majority of the
      animals by 11 days since the irradiation. The combination of the photothermal
      therapy with the immunoadjuvant cyclophosphamide resulted in increased survival.
      The in vivo results suggest the SWNT-AV/NIR treatment is a promising approach to
      treat breast cancer. 

PMID- 23975066
TI  - Teaching and assessing veterinary professionalism.
AB  - The teaching and assessment of professional behaviors and attitudes are important
      components of veterinary curricula. This article aims to outline some important
      considerations and concepts which will be useful for veterinary educators
      reviewing or developing this topic. A definition or framework of veterinary
      professionalism must be decided upon before educators can develop relevant
      learning outcomes. The interface between ethics and professionalism should be
      considered, and both clinicians and ethicists should deliver professionalism
      teaching. The influence of the hidden curriculum on student development as
      professionals should also be discussed during curriculum planning because it has
      the potential to undermine a formal curriculum of professionalism. There are
      several learning theories that have relevance to the teaching and learning of
      professionalism; situated learning theory, social cognitive theory, adult
      learning theory, reflective practice and experiential learning, and social
      constructivism must all be considered as a curriculum is designed. Delivery
      methods to teach professionalism are diverse, but the teaching of reflective
      skills and the use of early clinical experience to deliver valid learning
      opportunities are essential. Curricula should be longitudinal and integrated with
      other aspects of teaching and learning. Professionalism should also be assessed,
      and a wide range of methods have the potential to do so, including multisource
      feedback and portfolios. Validity, reliability, and feasibility are all important
      considerations. The above outlined approach to the teaching and assessment of
      professionalism will help ensure that institutions produce graduates who are
      ready for the workplace. 

PMID- 23975065
TI  - Three-dimensional observation of mouse tongue muscles using micro-computed
      tomography.
AB  - The aim of this study is to obtain information about the mouse tongue muscle
      rendered using micro-computed tomography (MUCT) at low, middle, and high
      magnifications. Three-dimensional (3D) MUCT is used in various fields. Most MUCT
      observations are restricted to hard tissue in biomaterial samples. Recently, with
      the use of osmium tetroxide, MUCT has been effectively employed to observe soft
      tissue; it is now believed that MUCT observation of soft tissue is feasible. On
      the other hand, the structure of the tongue muscle has been well studied, but
      cross-sectional imaging enhanced by 3D rendering is lacking. We chose the mouse
      tongue as a soft tissue case study for MUCT and generated cross-sectional images
      of the tongue enhanced by 3-D image rendering with histological resolution.
      During this observation, we developed new methods of low-magnification
      observation to show the relation between the tongue muscles and surrounding
      tissues. We also applied high-resolution MUCT in high-magnification observation
      of muscle fiber fascicles. Our methodological techniques give the following
      results: (1) For low-magnification observation (field of view: 12,000 MUm),
      pretreatment with decalcification and freeze drying is suitable for observing the
      area between the muscle of the tongue and the bone around the tongue using MUCT.
      (2) For middle-magnification observation (Field of view: 3,500 MUm), the use of
      osmium tetroxide to observe the muscle arrangement of the tongue by MUCT is
      suitable. (3) For high-magnification observation (Field of view: 450 MUm), high
      resolution MUCT is suitable for observation of the transversus muscle fiber
      fascicles. 

PMID- 23975067
TI  - Measuring the effectiveness of small-group and web-based training methods in
      teaching clinical communication: a case comparison study.
AB  - Current teaching approaches in human and veterinary medicine across North
      America, Europe, and Australia include lectures, group discussions, feedback,
      role-play, and web-based training. Increasing class sizes, changing learning
      preferences, and economic and logistical challenges are influencing the design
      and delivery of communication skills in veterinary undergraduate education. The
      study's objectives were to (1) assess the effectiveness of small-group and web
      based methods for teaching communication skills and (2) identify which training
      method is more effective in helping students to develop communication skills. At
      the Ross University School of Veterinary Medicine (RUSVM), 96 students were
      randomly assigned to one of three groups (control, web, or small-group training)
      in a pre-intervention and post-intervention group design. An Objective Structured
      Clinical Examination (OSCE) was used to measure communication competence within
      and across the intervention and control groups. Reliability of the OSCEs was
      determined by generalizability theory to be 0.65 (pre-intervention OSCE) and 0.70
      (post-intervention OSCE). Study results showed that (1) small-group training was
      the most effective teaching approach in enhancing communication skills and
      resulted in students scoring significantly higher on the post-intervention OSCE
      compared to the web-based and control groups, (2) web-based training resulted in
      significant though considerably smaller improvement in skills than small-group
      training, and (3) the control group demonstrated the lowest mean difference
      between the pre-intervention/post-intervention OSCE scores, reinforcing the need
      to teach communication skills. Furthermore, small-group training had a
      significant effect in improving skills derived from the initial phase of the
      consultation and skills related to giving information and planning. 

PMID- 23975068
TI  - Optimizing biomedical science learning in a veterinary curriculum: a review.
AB  - As veterinary medical curricula evolve, the time dedicated to biomedical science
      teaching, as well as the role of biomedical science knowledge in veterinary
      education, has been scrutinized. Aside from being mandated by accrediting bodies,
      biomedical science knowledge plays an important role in developing clinical,
      diagnostic, and therapeutic reasoning skills in the application of clinical
      skills, in supporting evidence-based veterinary practice and life-long learning,
      and in advancing biomedical knowledge and comparative medicine. With an
      increasing volume and fast pace of change in biomedical knowledge, as well as
      increased demands on curricular time, there has been pressure to make biomedical
      science education efficient and relevant for veterinary medicine. This has lead
      to a shift in biomedical education from fact-based, teacher-centered and
      discipline-based teaching to applicable, student-centered, integrated teaching.
      This movement is supported by adult learning theories and is thought to enhance
      students' transference of biomedical science into their clinical practice. The
      importance of biomedical science in veterinary education and the theories of
      biomedical science learning will be discussed in this article. In addition, we
      will explore current advances in biomedical teaching methodologies that are aimed
      to maximize knowledge retention and application for clinical veterinary training
      and practice. 

PMID- 23975069
TI  - Problem-based learning: facilitating multiple small teams in a large group
      setting.
AB  - Problem-based learning (PBL) is often described as resource demanding due to the
      high staff-to-student ratio required in a traditional PBL tutorial class where
      there is commonly one facilitator to every 5-16 students. The veterinary science
      program at Charles Sturt University, Australia, has developed a method of group
      facilitation which readily allows one or two staff members to facilitate up to 30
      students at any one time while maintaining the benefits of a small PBL team of
      six students. Multi-team facilitation affords obvious financial and logistic
      advantages, but there are also important pedagogical benefits derived from
      uniform facilitation across multiple groups, enhanced discussion and debate
      between groups, and the development of self-facilitation skills in students.
      There are few disadvantages to the roaming facilitator model, provided that
      several requirements are addressed. These requirements include a suitable venue,
      large whiteboards, a structured approach to support student engagement with each
      disclosure, a detailed facilitator guide, and an open, collaborative, and
      communicative environment. 

PMID- 23975070
TI  - Using educational games to engage students in veterinary basic sciences.
AB  - Educational games are an example of an active learning teaching technique based
      on Kolb's learning cycle. We have designed multiple games to provide concrete
      experiences for social groups of learners in the basic sciences. "Antimicrobial
      Set" is a card game that illustrates global patterns in antimicrobial therapy.
      "SHOCK!" is a card game designed to enhance student understanding of the four
      types of hypersensitivity reactions. After each game is played, students undergo
      a structured debriefing session with faculty members to further enhance their
      self-reflective skills. "Foodborne Outbreak Clue" utilizes the famous Parker
      Brothers(r) board game as a means to practice skills associated with outbreak
      investigation and risk assessment. This game is used as a review activity and fun
      application of epidemiologic concepts. Anecdotal feedback from students suggests
      that they enjoyed the activities. Games such as these can be easily implemented
      in large- or small-group settings and can be adapted to other disciplines as
      needed. 

PMID- 23975071
TI  - Online tools for teaching evidence-based veterinary medicine.
AB  - Evidence-based veterinary medicine (EBVM) is of interest and relevance to
      veterinary practitioners. Consequently, veterinary schools take responsibility
      for teaching students how to appraise scientific articles and for equipping them
      with the skills needed to obtain and evaluate the best evidence and to apply this
      approach to their own cases. As part of our farm animal clinical rotation, we
      train students in qualitative and quantitative EBVM methods using an e-learning
      environment, online teaching materials, a wiki (a Web site that allows its users
      to edit its content via a Web browser), and face-to-face tutorials that support
      learning. Students working in small groups use a wiki to record details of the
      history, clinical presentation, diagnostic tests, herd data, and management plans
      for their chosen farm animal clinical cases. Using a standardized patient,
      intervention, comparison, and outcome (PICO) format, each group formulates a
      patient question based on either a proposed intervention or diagnostic procedure
      for the case and conducts an online scientific literature database search. The
      students appraise the articles retrieved using EBVM approaches and record the
      information in the wiki. The summation of this body of work, the group's
      critically appraised topic (CAT), includes the original PICO, a standardized
      table of the scientific evidence for the effectiveness of the intervention or
      diagnostic procedure, a summary statement in the form of a clinical bottom line,
      and their reflections upon the CAT. At the end of the rotation, students take
      part in a structured "CAT Club" where they present and discuss their findings
      with fellow students and clinicians. 

PMID- 23975072
TI  - Evaluation of a training model to teach veterinary students a technique for
      injecting the jugular vein in horses.
AB  - In this study, a newly-developed model for training veterinary students to inject
      the jugular vein in horses was evaluated as an additional tool to supplement the
      current method of teaching. The model was first validated by 19 experienced
      equine veterinarians, who judged the model to be a realistic and valuable tool
      for learning the technique. Subsequently, it was assessed using 24 students who
      were divided randomly into two groups. The injection technique was taught
      conventionally in a classroom lecture and a live demonstration to both groups,
      but only group 1 received additional training on the new model. All participants
      filled out self-assessment questionnaires before and after group 1 received
      training on the model. Finally, the proficiency of both groups was assessed using
      an objective structured clinical evaluation (OSCE) on live horses. Students from
      group 1 showed significantly improved confidence after their additional training
      on the model and also showed greater confidence when compared to group 2
      students. In the OSCE, group 1 had a significantly better score compared to group
      2: the median (with inter-quartile range) was 15 (0.7) vs. 11.5 (2.8) points out
      of 15, respectively. The training model proved to be a useful tool to teach
      veterinary students how to perform jugular vein injections in horses in a
      controlled environment, without time limitations or animal welfare concerns. The
      newly developed training model offers an inexpensive, efficient, animal-sparing
      way to teach this clinical skill to veterinary students. 

PMID- 23975073
TI  - Veterinary medical student well-being: depression, stress, and personal
      relationships.
AB  - Existing research consistently connects higher relationship satisfaction with
      improved psychological and physical functioning. Investigations focusing on
      relational satisfaction within veterinary medicine have been sparse. This study
      evaluated 240 veterinary medical students at Kansas State University. Results
      indicate that students within higher-functioning relationships are more likely to
      report fewer depressive symptoms, lower stress associated with balancing their
      school and home lives, less relationship conflict, better physical health, and
      improved ability to cope with academic expectations, while at the same time
      experiencing more stress from being behind in studies. Based on these findings,
      Colleges of Veterinary Medicine (CVMs) are encouraged to institute policies and
      programs which foster relationship-building for students. 

PMID- 23975074
TI  - What are the clinical questions of practicing veterinarians?
AB  - Clinical questions are central to learning among veterinarians and drive informal
      learning during clinical practice. We set out to classify the clinical questions
      of practicing veterinarians using a taxonomy previously validated in human
      medicine. This prospective observational study used a convenience sample of 12
      veterinarians in private, small-animal practices. We used three methods to gather
      clinical questions from the veterinarians: direct observation (asking
      veterinarians after each encounter), self-report via e-mail, and self-report via
      data-collection pocket cards. We then classified these questions using a
      validated taxonomy of question types, as well as by clinical category. A total of
      157 clinical questions were collected; 99 were about dogs, 33 were about cats,
      and 25 were about multiple species or did not specify a species. Nearly half of
      the questions were rated as high priority, and only 11.5% as low priority. Over
      half of the questions (53%) were about treatment and 20% were about diagnosis.
      The two most common question types were "Is drug X indicated in situation Y or
      for condition Y?" and "How should I treat finding/condition Y (given situation
      Z)?" Overall, 5 of 57 question-type categories accounted for over half of the
      questions. The most common clinical categories were pharmacology, endocrine,
      musculoskeletal, and general surgery. This is the first study to systematically
      identify and classify the clinical questions of veterinarians. A better
      understanding of these questions can be used to inform the development of
      continuing-education (CE) activities that are directly responsive to the
      information needs of participants. 

PMID- 23975075
TI  - Reported rabies pre-exposure immunization of students at US Colleges of
      Veterinary Medicine.
AB  - In 2008, the US experienced a disruption in human rabies vaccine supplies,
      leading public health authorities to prioritize vaccine release for post-exposure
      prophylaxis (PEP) and limit vaccine supplies for pre-exposure prophylaxis (PreEP)
      in high-risk groups. In 2008, the Association of American Veterinary Medical
      Colleges (AAVMC) surveyed its member institutions on rabies vaccination policies
      and practices. Senior administrators at Colleges of Veterinary Medicine (CVMs)
      and departments of veterinary science and comparative medicine were asked to
      identify the person most knowledgeable about their institution's student rabies
      vaccination program. Respondents were asked to describe their policies and
      procedures for administering PreEP to veterinary medical students and staff and
      to estimate the annual demand for student and staff PreEP vaccine. Twenty-one
      CVMs responded. Twenty (95%) reported requiring PreEP of veterinary medical
      students and 16 (80%) of those 20 required vaccination upon matriculation. An
      estimated 7,309 doses of vaccine were required for PreEP of an estimated 2,436
      first-year US veterinary medical students. Seventy-two percent of respondents
      administered PreEP in August, September, and October, coinciding with the highest
      public demand for PEP. CVMs should consider altering the timing of rabies vaccine
      administration to veterinary medical students and staff to other months, thereby
      helping to ensure that PEP rabies vaccine will be available to people with
      validated rabies exposures and to ensure that supplies will be available for
      PreEP of students and staff. AAVMC may wish to identify and support a point of
      coordination to facilitate the purchase and distribution of human rabies vaccine
      among its US member CVMs. 

PMID- 23975076
TI  - From theory to practice: integrating instructional technology into veterinary
      medical education.
AB  - Technology has changed the landscape of teaching and learning. The integration of
      instructional technology into teaching for meaningful learning is an issue for
      all educators to consider. In this article, we introduce educational theories
      including constructivism, information-processing theory, and dual-coding theory,
      along with the seven principles of good practice in undergraduate education. We
      also discuss five practical instructional strategies and the relationship of
      these strategies to the educational theories. From theory to practice, the
      purpose of the article is to share our application of educational theory and
      practice to work toward more innovative teaching in veterinary medical education.

PMID- 23975077
TI  - Peer-assisted communication training: veterinary students as simulated clients
      and communication skills trainers.
AB  - Mounting research supports the use of peer-assisted learning (PAL) as a teaching
      method in human and veterinary medicine. PAL can be a cost-efficient educational
      tool, saving both financial resources and faculty time. This article reviews a
      PAL model for teaching communication skills to veterinary medical students. In
      this model, junior veterinary students served as simulated clients for sophomore
      veterinary students. Details regarding methods of program delivery as well as
      evaluation data are presented. Differences between two student cohorts who
      participated in the PAL educational model and their subsequent evaluation results
      are discussed. Overall, veterinary medical students reported that this approach
      was beneficial and that the topic was critical to their success as veterinarians.
      Students also showed improvement in communication knowledge and reported that
      peer feedback was a strength of the program. Finally, future directions to assess
      and strengthen the use of PAL for communication training in veterinary medical
      education are proposed. 

PMID- 23975078
TI  - Externalizing disorders in adolescence mediate the effects of maternal depression
      on substance use disorders.
AB  - Maternal depression has been linked to increased risk of substance use disorders
      (SUDs) in offspring. Cross-sectional studies have identified relationships among
      maternal depression, externalizing disorders and SUDs, but no longitudinal
      examination of causality has been undertaken. In order to address this gap in the
      literature, depression and externalizing disorders at or prior to age 15 were
      tested as mediators of the relationship between maternal depression and SUDs
      diagnosed between ages 16 and 20 in a sample of 702 Australian youth (363 women)
      using path models. Mothers' and fathers' substance diagnoses and earlier onset of
      substance abuse in youth were controlled for in all analyses. Consistent with
      previous work, maternal depression predicted SUDs between ages 16 and 20. An
      indirect effect of maternal depression through youth externalizing disorders
      diagnosed by age 16 was detected for alcohol and cannabis use disorders, but not
      drug disorders. Early adolescent depression was not a mediator of the
      relationship between maternal depression and any of the substance outcomes
      measured. To our knowledge, this study is the first to examine depression and
      externalizing disorders in early adolescence as mediators of the effect of
      maternal depression on psychopathology in later adolescence. Further work is
      needed to understand how family environment and genetic factors may explain the
      mediation by externalizing disorders. 

PMID- 23975080
TI  - Clinical features of sellar and suprasellar meningiomas.
AB  - Meningiomas account for about 1% of sellar masses. Although they can mimic
      pituitary adenomas, they are more vascularized and invasive. To gain insights
      that would enhance our ability to establish a pre-surgical diagnosis of
      meningioma, we performed a retrospective study of these tumors. Query of the
      surgical pathology database identified 1,516 meningiomas operated at out
      institution between January 2000 and May 2012. Cases were matched to the
      radiology database to identify a strictly defined sellar and/or suprasellar
      location. We identified 57 meningiomas. F:M ratio was 6:1. The mean age was 52
      years (median 50, range 30-78). The most common symptoms were visual disturbance
      (58%), headache (16%) and incidental finding (12%). The mean duration of symptoms
      was 13 months. Hyperprolactinemia was found in 36%, with mean value of 51.6 ng/ml
      (median 41.8, range 22.5-132). Mean maximal diameter was 2.9 cm (median 2.7,
      range 0.9-6.8), and most tumors enhanced homogeneously on MRI after gadolinium. A
      "dural tail" sign was reported in a third. The radiologist reported "likely
      meningioma" in 65%, "possible meningioma" in 8.7%, and pituitary adenoma in 11%.
      After surgery, visual disturbances improved in most patients (80%) but headache
      only in 7%. Post-operative complications at 1 and 3 months occurred 38.6 and
      33.3% respectively. There was no mortality. Sellar/suprasellar meningiomas
      represent 4% of all meningiomas, and have a particularly high female
      predominance. The diagnosis is suggested by the radiologist in approximately 2/3
      of the cases. An improved method to differentiate preoperatively these tumors
      from adenomas would be desirable.

PMID- 23975081
TI  - Low-dose, prophylactic, extended-field, intensity-modulated radiotherapy plus
      concurrent weekly cisplatin for patients with stage IB2-IIIB cervical cancer,
      positive pelvic lymph nodes, and negative para-aortic lymph nodes.
AB  - OBJECTIVE: The objective of this study was to assess prospectively the clinical
      outcomes of low-dose prophylactic extended-field, intensity-modulated
      radiotherapy (IMRT) plus concurrent weekly cisplatin for patients with stage IB2
      IIIB cervical cancer, positive pelvic lymph nodes (PLNs), and negative para
      aortic lymph nodes (PALNs). METHODS: Thirty-two patients with stage IB2-IIIB
      cervical cancer with positive PLN and negative PALN were included prospectively.
      All lymph nodes were assessed with positron emission tomography. The PALN field,
      including lymphatics from the superior border of L1 to the L4-L5 interphase, was
      irradiated concurrently with pelvic IMRT with a prescribed dose of 40 Gy in 25
      fractions. Chemotherapy consisted of cisplatin delivered weekly at a dose of 40
      mg/m. Using historical controls treated with pelvic radiotherapy, the survival
      curves were compared to assess the difference between the 2 treatment periods.
      RESULTS: Thirty-one patients completed the allocated extended-field IMRT, and all
      finished the planned pelvic IMRT and brachytherapy. Acute >= grade 3
      gastrointestinal, genitourinary, and hematologic toxicities were seen in 2, 1,
      and 18 patients, respectively. During a median follow-up of 33 months, 5 patients
      developed out-field distant recurrences. One patient had a late grade 3
      gastrointestinal complication, and 1 patient had genitourinary toxicity. The 3
      year actuarial overall survival, disease-free survival, and distant metastasis
      free survival for the study cohort and historic controls were 87% versus 62% (P =
      0.02), 82% versus 54% (P = 0.02), and 79% versus 57% (P = 0.01), respectively.
      CONCLUSIONS: Extended-field IMRT of 40 Gy to the PALN plus concurrent cisplatin
      can effectively eradicate subclinical disease at the PALN and improve the outcome
      for patients with PLN-positive stage IB2-IIIB cervical cancer.

PMID- 23975079
TI  - What causes internalising traits and autistic traits to co-occur in adolescence?
      A community-based twin study.
AB  - Autism shows a high degree of comorbidity with anxiety disorders. Adolescence is
      a time of increased stress and vulnerability to internalising problems. This
      study addresses for the first time the degree of genetic and environmental
      overlap between autistic traits (total measure and subscales) and internalising
      traits in a community-based adolescent twin sample. Parents of 12-14-year-old
      twins (N = 3,232 pairs; 3,460 males, 3,004 females) reported on the twins'
      internalising and autistic traits. Autistic trait subscales were created using
      principal component analysis. Bivariate twin model-fitting was conducted.
      Autistic and internalising traits correlated moderately (r = 0.30). Genetic
      influences on individual traits were substantial but genetic overlap between
      traits was moderate (genetic correlation: males = 0.30, females = 0.12). Shared
      environmental influences were low for internalising traits and moderate for
      autistic traits, and showed considerable overlap (shared environmental
      correlation: males = 0.53, females = 1). Nonshared environmental influences were
      moderate for internalising traits and low for autistic traits and showed low
      overlap. A multiple component solution was found for autistic traits and of the
      derived subscales, autistic-like 'Social Unease' showed the most phenotypic and
      genetic overlap with internalising traits. 

PMID- 23975082
TI  - Added value of family history in counseling about risk of BRCA1/2 mutation in
      early-onset epithelial ovarian cancer.
AB  - OBJECTIVES: Epithelial ovarian cancer in women 40 years or younger is rare;
      diagnosis at this age justifies referral for genetic testing. We evaluated
      clinical data, family history, and risk of identifying BRCA1/2 mutations in women
      with early-onset epithelial ovarian cancer. MATERIALS/METHODS: Women 40 years or
      younger with epithelial ovarian cancer tested for BRCA1/2 mutation at our
      department of human genetics between 1996 and 2012 were included. The rate of
      BRCA1/2 mutation was obtained; carriers were compared to noncarriers regarding
      clinical data. RESULTS: Ten (19%) of 52 women had a BRCA1/2 mutation. This
      mutation was detected in 67% of women with and in 9% of the women without first
      degree relatives with breast and/or ovarian cancer (P < 0.001; Fisher exact
      test). The median age at diagnosis was lower in the noncarriers compared to the
      carriers (30 vs 38 years; P = 0.014). Among the BRCA1/2 mutation carriers, 60%
      had serous tumors, 80% had moderately to poorly differentiated tumors, and 70%
      had International Federation of Gynecology and Obstetrics stage III/IV compared
      to 55%, 43%, and 45%, respectively, in the noncarriers. CONCLUSIONS: The risk of
      finding a BRCA1/2 mutation in women 40 years or younger is comparable to women of
      all ages with epithelial ovarian cancer. Prior probability of finding a BRCA1/2
      mutation in these young women is largely determined by their family history,
      which can help caregivers in informing ahead of genetic counseling and testing.

PMID- 23975083
TI  - Computational analysis of high-dimensional flow cytometric data for diagnosis and
      discovery.
AB  - Recent technological advancements have enabled the flow cytometric measurement of
      tens of parameters on millions of cells. Conventional manual data analysis and
      bioinformatics tools cannot provide a complete analysis of these datasets due to
      this complexity. In this chapter we will provide an overview of a general data
      analysis pipeline both for automatic identification of cell populations of known
      importance (e.g., diagnosis by identification of predefined cell population) and
      for exploratory analysis of cohorts of flow cytometry assays (e.g., discovery of
      new correlates of a malignancy). We provide three real-world examples of how
      unsupervised discovery has been used in basic and clinical research. We also
      discuss challenges for evaluation of the algorithms developed for (1)
      identification of cell populations using clustering, (2) identification of
      specific cell populations, and (3) supervised analysis for discriminating between
      patient subgroups. 

PMID- 23975084
TI  - Determination of avilamycin as dichloroisoeverninic acid in poultry and porcine
      muscles by isotope dilution liquid chromatography-tandem mass spectrometry.
AB  - Avilamycin residue in food is regulated as its marker residue
      dichloroisoeverninic acid (DIA). An isotope dilution liquid chromatography-tandem
      mass spectrometry method is established for the accurate determination of DIA in
      animal muscles without any pre-extraction and preconcentration prior to alkaline
      hydrolysis. Optimization of the sample cleanup procedures such as liquid-liquid
      extraction and solid phase extraction was performed by fine-tuning several
      critical parameters to reduce the matrix effects. Quantification of DIA in edible
      muscle was accomplished by using matrix-matched calibration with
      dichloroisoeverninic acid-d6 as internal standard. The method was validated with
      DIA and avilamycin-fortified poultry and porcine muscles at three different
      levels (25, 50, and 100 MUg/kg). Conversion of avilamycin to DIA by alkaline
      hydrolysis was >=92%. The recoveries of DIA in both muscles at three
      fortification levels ranged from 94 to 106% and RSDs were <=11% in all cases. The
      estimated limit of detection values in poultry and porcine muscles were 2.7 and
      0.7 MUg/kg, respectively. The estimated limit of quantitation values in poultry
      and porcine muscles were 8.3 and 2.4 MUg/kg, respectively. This method is
      suitable for routine monitoring of avilamycin residue in food safety surveillance
      programs.

PMID- 23975085
TI  - Separation and composition distribution determination of triblock copolymers by
      thermal field-flow fractionation.
AB  - Thermal field-flow fractionation (ThFFF) is used to separate a linear triblock
      copolymer of polystyrene, poly(tert-butyl acrylate), and poly(methyl
      methacrylate) by composition. Fractions were collected and subjected to off-line
      NMR analysis. The resultant mole fraction versus retention time plots for each of
      the three polymer components confirmed the success of the separation and yielded
      the composition distribution of the copolymer. The composition distribution was
      also obtained using a second approach that involved solving a series of equations
      comprised of polymer thermal diffusion coefficients and quasi-elastic light
      scattering, differential refractometry, and UV detector responses. Both sets of
      data showed similar trends of composition variations in each polymer component as
      a function of retention time. However, discrepancies were observed in the mole
      fraction values. The ability to compositionally separate and to determine
      composition distribution of copolymers is important as demonstrated by the
      presence of diblock impurities in the ThFFF with off-line NMR results. 

PMID- 23975086
TI  - Development of an adapted version of polar organic chemical integrative samplers
      (POCIS-Nylon).
AB  - POCIS (polar organic chemical integrative samplers) are increasingly used for
      sampling polar compounds. Although very efficient for a wide range of pollutants,
      the classic configuration of the device has a number of limitations, in
      particular for the sampling of highly polar analytes and hydrophobic compounds.
      This study presents a new version of the POCIS passive sampler which uses a
      highly porous Nylon membrane of 30 MUm pore size, enabling the sampling of
      hydrophobic pollutants and improving the accumulation rate of other pollutants.
      This newly designed tool and the classic POCIS were both tested during a
      laboratory experiment to evaluate the accumulation kinetics of a selection of
      pesticides and pharmaceuticals. The observed results show unexpected accumulation
      kinetics for the new version of POCIS. To explain the data, the use of an
      intraparticulate diffusion model was required, which also enabled us to propose
      another explanation of the burst effect observed with the classic POCIS,
      primarily related to the potential wetting of the device as the first step in the
      accumulation of compounds.

PMID- 23975087
TI  - Time-resolved fluorescence microscopy for quantitative Ca2+ imaging in living
      cells.
AB  - Calcium (Ca(2+)) is a ubiquitous intracellular second messenger and involved in a
      plethora of cellular processes. Thus, quantification of the intracellular Ca(2+)
      concentration ([Ca(2+)]i) and of its dynamics is required for a comprehensive
      understanding of physiological processes and potential dysfunctions. A powerful
      approach for studying [Ca(2+)]i is the use of fluorescent Ca(2+) indicators. In
      addition to the fluorescence intensity as a common recording parameter, the
      fluorescence lifetime imaging microscopy (FLIM) technique provides access to the
      fluorescence decay time of the indicator dye. The nanosecond lifetime is mostly
      independent of variations in dye concentration, allowing more reliable
      quantification of ion concentrations in biological preparations. In this study,
      the feasibility of the fluorescent Ca(2+) indicator Oregon Green Bapta-1 (OGB-1)
      for two-photon fluorescence lifetime imaging microscopy (2P-FLIM) was evaluated.
      In aqueous solution, OGB-1 displayed a Ca(2+)-dependent biexponential
      fluorescence decay behaviour, indicating the presence of a Ca(2+)-free and Ca(2+)
      bound dye form. After sufficient dye loading into living cells, an in situ
      calibration procedure has also unravelled the Ca(2+)-free and Ca(2+)-bound dye
      forms from a global biexponential fluorescence decay analysis, although the dye's
      Ca(2+) sensitivity is reduced. Nevertheless, quantitative [Ca(2+)]i recordings
      and its stimulus-induced changes in salivary gland cells could be performed
      successfully. These results suggest that OGB-1 is suitable for 2P-FLIM
      measurements, which can gain access to cellular physiology. 

PMID- 23975088
TI  - Determination of acetamiprid partial-intercalative binding to DNA by use of
      spectroscopic, chemometrics, and molecular docking techniques.
AB  - Acetamiprid (ACT) is an insecticide widely used for controlling a variety of
      insect pests. The binding mode associated with calf thymus DNA (ctDNA) upon
      interaction with ACT was determined using spectroscopic, chemometrics, and
      molecular docking techniques to clarify the interaction mechanism at the
      molecular level. Fluorescence titration suggested that the fluorescence quenching
      of ACT by ctDNA is a static procedure. The binding constants between ACT and
      ctDNA at different temperatures were calculated to be of the order 10(3)-10(4) L
      mol(-1). The positive values of enthalpy and entropy change suggested that the
      binding process is primarily driven by hydrophobic interactions. Multivariate
      curve resolution-alternating least squares (MCR-ALS), a chemometrics approach,
      was used to resolve the expanded UV-visible spectral data matrix. The
      concentration profiles and the spectra for the three reaction components (ACT,
      ctDNA, and ACT-ctDNA complex) of the system, which formed a highly overlapping
      composite response, were then successfully obtained and used to evaluate the
      progress of ACT interacting with ctDNA. The results of the single-stranded ctDNA
      and iodide quenching experiments, ctDNA-melting investigations, and viscosity
      measurements indicated that ACT binds to ctDNA by means of a partial
      intercalation. Molecular docking studies showed that the specific binding site is
      mainly located between the ACT and G-C base pairs of ctDNA. This docking
      prediction was confirmed by use of Fourier-transform infrared (FT-IR) spectral
      analysis. Results from circular dichroism (CD) spectroscopy revealed that ACT
      induced a conformational change from the B-ctDNA form to the A-ctDNA form. 

PMID- 23975089
TI  - Batch profiling calibration for robust NMR metabonomic data analysis.
AB  - Metabonomic studies involve the analysis of large numbers of samples to identify
      significant changes in the metabolic fingerprints of biological systems, possibly
      with sufficient statistical power for analysis. While procedures related to
      sample preparation and spectral data acquisition generally include the use of
      independent sample batches, these might be sources of systematic variation whose
      effects should be removed to focus on phenotyping the relevant biological
      variability. In this work, we describe a grouped-batch profile (GBP) calibration
      strategy to adjust nuclear magnetic resonance (NMR) metabolomic data-sets for
      batch effects either introduced during NMR experiments or samples work-up. We
      show how this method can be applied to data calibration in the context of a large
      scale NMR epidemiological study where quality control samples are available. We
      also illustrate the efficiency of a batch profile correction for NMR metabonomic
      investigation of cell extracts, where GBP can significantly improve the
      predictive power of multivariate statistical models for discriminant analysis of
      the cell infection status. The method is applicable to a broad range of NMR
      metabolomic/metabonomic cohort studies. 

PMID- 23975090
TI  - Toward a comprehensive and systematic methylome signature in colorectal cancers.
AB  - CpG Island Methylator Phenotype (CIMP) is one of the underlying mechanisms in
      colorectal cancer (CRC). This study aimed to define a methylome signature in CRC
      through a methylation microarray analysis and a compilation of promising CIMP
      markers from the literature. Illumina HumanMethylation27 (IHM27) array data was
      generated and analyzed based on statistical differences in methylation data (1st
      approach) or based on overall differences in methylation percentages using lower
      95% CI (2nd approach). Pyrosequencing was performed for the validation of nine
      genes. A meta-analysis was used to identify CIMP and non-CIMP markers that were
      hypermethylated in CRC but did not yet make it to the CIMP genes' list. Our 1st
      approach for array data analysis demonstrated the limitations in selecting genes
      for further validation, highlighting the need for the 2nd bioinformatics approach
      to adequately select genes with differential aberrant methylation. A more
      comprehensive list, which included non-CIMP genes, such as APC, EVL, CD109, PTEN,
      TWIST1, DCC, PTPRD, SFRP1, ICAM5, RASSF1A, EYA4, 30ST2, LAMA1, KCNQ5, ADHEF1, and
      TFPI2, was established. Array data are useful to categorize and cluster colonic
      lesions based on their global methylation profiles; however, its usefulness in
      identifying robust methylation markers is limited and rely on the data analysis
      method. We have identified 16 non-CIMP-panel genes for which we provide rationale
      for inclusion in a more comprehensive characterization of CIMP+ CRCs. The
      identification of a definitive list for methylome specific genes in CRC will
      contribute to better clinical management of CRC patients. 

PMID- 23975091
TI  - Ultrasonography in myofascial neck pain: randomized clinical trial for diagnosis
      and follow-up.
AB  - OBJECTIVE: A definitive diagnosis of chronic neck pain (CNP) is sometimes not
      possible. The aim of this study was to understand the possible role of the deep
      fasciae in CNP and the utility of the ultrasonography in the diagnosis of
      myofascial neck pain. METHODS: The morphometric and clinical data of 25 healthy
      subjects and 28 patients with CNP were compared. For all subjects, the active and
      passive cervical range of motion (ROM) was analyzed and the neck pain disability
      questionnaire (NDPQ) was administered. The fascial thickness of the sternal
      ending of the sternocleidomastoid and medial scalene muscles was also analyzed by
      ultrasonography. RESULTS: There were significant differences between healthy
      subjects and patients with CNP in the thickness of the upper side of the
      sternocleidomastoid fascia and the lower and upper sides of the right scalene
      fascia both at the end of treatment as during follow-up. A significant decrease
      in pain and thickness of the fasciae were found. Analysis of the thickness of the
      sub-layers showed a significant decrease in loose connective tissue, both at the
      end of treatment and during follow-up. CONCLUSIONS: The data support the
      hypothesis that the loose connective tissue inside the fasciae may plays a
      significant role in the pathogenesis of CNP. In particular, the value of 0.15 cm
      of the SCM fascia was considered as a cut-off value which allows the clinician to
      make a diagnosis of myofascial disease in a subject with CNP. The variation of
      thickness of the fascia correlated with the increase in quantity of the loose
      connective tissue but not with dense connective tissue.

PMID- 23975092
TI  - An interesting case of bilateral bifid insertion of superior rectus muscle as an
      intra-operative finding in a patient with oculocutaneous albinism.
AB  - We report a case of bilateral bifid insertion of superior rectus muscles, in a
      patient with oculocutaneous albinism as an incidental intraoperative finding
      during eye muscle surgery. The muscle was successfully operated on and the
      patient did well postoperatively. To our knowledge, this is the first report of
      this anomaly. 

PMID- 23975093
TI  - Investigation of MTHFR C677T gene polymorphism, biochemical and clinical
      parameters in Turkish migraine patients: association with allodynia and fatigue.
AB  - We investigated whether there is any relationship between biochemical and
      clinical parameters of migraine and methylenetetrahydrofolate reductase (MTHFR)
      gene C677T polymorphism, associated with the migraine subtypes, symptoms, and
      gender. A total of 150 migraine patients with and without aura (MA and MO) and
      107 non-sufferers were included in the study. Biochemical and clinical parameters
      were measured and genetic analysis was performed. The MTFHR C677T genotype was
      significantly higher in the migraine group (p = 0.000). The CT genotype frequency
      of individuals with a family history of migraine was significantly higher (p =
      0.025). This genotype frequency was higher in patients who suffer from
      compression, allodynia, fatigue, and sleeplessness (p = 0.027, 0.023, 0.006, and
      0.05, respectively). Homocysteine and total cholesterol levels were significantly
      higher in the migraine group than the control group (p = 0.007 and 0.010,
      respectively). However, the other biochemical and clinical parameters did not
      differ from each other (p > 0.05), with only attack frequency being significantly
      higher in the MO group (p = 0.005). While the folate and HDL levels were
      significantly higher in females (p = 0.001 and 0.000, respectively), the
      homocysteine and triglyceride levels were significantly higher in males (p =
      0.000 for each one). BMIs were significantly lower in the control than the
      migraine group (p = 0.021); however, an association between the C677T variant and
      BMI was not found (p = 0.787) in the migraine group. An association between the
      MTHFR C667T polymorphism and migraine susceptibility was found. Additional
      studies including genetic, clinic, and biochemical parameters should be conducted
      to better understand the disease.

PMID- 23975095
TI  - Clonidine suppresses the induction of long-term potentiation by inhibiting HCN
      channels at the Schaffer collateral-CA1 synapse in anesthetized adult rats.
AB  - Activation of alpha2-adrenoceptors inhibits long-term potentiation and long-term
      depression in many brain regions. However, effectiveness and mechanism of alpha2
      adrenoceptors for synaptic plasticity at the Schaffer collateral-CA1 synapses in
      rat in vivo is unclear. In the present study, we investigated the effects of
      alpha2-adrenoceptors agonist clonidine on high-frequency stimulation (HFS)
      induced long-term potentiation (LTP) and paired-pulse facilitation (PPF) at the
      Schaffer collateral-CA1 synapse of rat hippocampus in vivo. Clonidine (0.05, 0.1
      mg/kg, ip) inhibited synaptic plasticity in a dose-dependent manner, accompanying
      with the decreasing of aortic pressure and heart rate (HR) in anesthetized rats.
      Clonidine (1.25, 2.5 MUg/kg, icv, 10 min before HFS) also dose-dependently
      inhibited synaptic plasticity, which had no remarkable effect on HR and aortic
      pressure. But, 20 min after HFS, administration of clonidine (2.5 MUg/kg) had no
      effect on LTP. The inhibitory effect of clonidine (2.5 MUg/kg) on LTP was
      completely reversed by yohimbine (18 MUg/kg, icv) and ZD7288 (5 MUg/kg, icv).
      Moreover, the inhibition was accompanied by a significant increase of the
      normalized PPF ratio. Furthermore, clonidine at 1 and 10 MUM significantly
      decreased glutamate (Glu) content in the culture supernatants of hippocampal
      neurons, and yohimbine at 1 and 10 MUM had no effect on Glu release, while it
      could reverse the inhibition of clonidine (1 and 10 MUM) on Glu release. In
      conclusion, clonidine can suppress the induction of LTP at the Schaffer
      collateral-CA1 synapse, and the possible mechanism is that activation of
      presynaptic alpha2-adrenoceptors reduces the Glu release by inhibiting HCN
      channels.

PMID- 23975094
TI  - Neuroprotective potential of Bacopa monnieri and Bacoside A against dopamine
      receptor dysfunction in the cerebral cortex of neonatal hypoglycaemic rats.
AB  - Neonatal hypoglycaemia initiates a series of events leading to neuronal death,
      even if glucose and glycogen stores return to normal. Disturbances in the
      cortical dopaminergic function affect memory and cognition. We recommend Bacopa
      monnieri extract or Bacoside A to treat neonatal hypoglycaemia. We investigated
      the alterations in dopaminergic functions by studying the Dopamine D1 and D2
      receptor subtypes. Receptor-binding studies revealed a significant decrease (p <
      0.001) in dopamine D1 receptor number in the hypoglycaemic condition, suggesting
      cognitive dysfunction. cAMP content was significantly (p < 0.001) downregulated
      in hypoglycaemic neonatal rats indicating the reduction in cell signalling of the
      dopamine D1 receptors. It is attributed to the deficits in spatial learning and
      memory. Hypoglycaemic neonatal rats treated with Bacopa extract alone and
      Bacoside A ameliorated the dopaminergic and cAMP imbalance as effectively as the
      glucose therapy. The upregulated Bax expression in the present study indicates
      the high cell death in hypoglycaemic neonatal rats. Enzyme assay of SOD confirmed
      cortical cell death due to free radical accumulation. The gene expression of SOD
      in the cortex was significantly downregulated (p < 0.001). Bacopa treatment
      showed a significant reversal in the altered gene expression parameters (p <
      0.001) of Bax and SOD. Our results suggest that in the rat experimental model of
      neonatal hypoglycaemia, Bacopa extract improved alterations in D1, D2 receptor
      expression, cAMP signalling and cell death resulting from oxidative stress. This
      is an important area of study given the significant motor and cognitive
      impairment that may arise from neonatal hypoglycaemia if proper treatment is not
      implemented.

PMID- 23975096
TI  - Agonist binding to the GluK5 subunit is sufficient for functional surface
      expression of heteromeric GluK2/GluK5 kainate receptors.
AB  - Trafficking of ionotropic glutamate receptors to the plasma membrane commonly
      requires occupation of the agonist binding sites. This quality control check does
      not typically involve receptor activation, as binding by competitive antagonists
      or to non-functional channels may also permit surface expression. The tetrameric
      kainate receptors can be assembled from five different subunits (GluK1-GluK5).
      While the "low-affinity" GluK1-3 subunits are able to produce functional
      homomeric receptors, the "high-affinity" GluK4 and GluK5 subunits require co
      assembly with GluK1, 2, or 3 for surface expression. These two different types of
      subunits have distinct functional roles in the receptor. Therefore, we examined
      the relative importance of occupancy of the agonist site of the GluK2 or GluK5
      subunit for surface expression of heteromeric receptors. We created subunits with
      a mutation within the S2 ligand-binding domain which decreased agonist affinity.
      Mutations at this site reduced functional surface expression of homomeric GluK2
      receptors, but surface expression of these receptors could be increased with
      either a competitive antagonist or co-assembly with wild-type GluK5. In contrast,
      mutations in the GluK5 subunit reduced the production of functional heteromeric
      receptors at the membrane, and could not be rescued with either an antagonist or
      wild-type GluK2. These findings indicate that ligand binding to only the GluK5
      subunit is both necessary and sufficient to allow trafficking of recombinant
      GluK2/K5 heteromers to the cell membrane, but that occupancy of the GluK2 site
      alone is not. Our results suggest a distinct role for the GluK5 subunit in
      regulating surface expression of heteromeric kainate receptors.

PMID- 23975097
TI  - DNA damage in germ cells induces an innate immune response that triggers systemic
      stress resistance.
AB  - DNA damage responses have been well characterized with regard to their cell
      autonomous checkpoint functions leading to cell cycle arrest, senescence and
      apoptosis. In contrast, systemic responses to tissue-specific genome instability
      remain poorly understood. In adult Caenorhabditis elegans worms germ cells
      undergo mitotic and meiotic cell divisions, whereas somatic tissues are entirely
      post-mitotic. Consequently, DNA damage checkpoints function specifically in the
      germ line, whereas somatic tissues in adult C. elegans are highly radio
      resistant. Some DNA repair systems such as global-genome nucleotide excision
      repair (GG-NER) remove lesions specifically in germ cells. Here we investigated
      how genome instability in germ cells affects somatic tissues in C. elegans. We
      show that exogenous and endogenous DNA damage in germ cells evokes elevated
      resistance to heat and oxidative stress. The somatic stress resistance is
      mediated by the ERK MAP kinase MPK-1 in germ cells that triggers the induction of
      putative secreted peptides associated with innate immunity. The innate immune
      response leads to activation of the ubiquitin-proteasome system (UPS) in somatic
      tissues, which confers enhanced proteostasis and systemic stress resistance. We
      propose that elevated systemic stress resistance promotes endurance of somatic
      tissues to allow delay of progeny production when germ cells are genomically
      compromised. 

PMID- 23975098
TI  - The structural mechanism of KCNH-channel regulation by the eag domain.
AB  - The KCNH voltage-dependent potassium channels (ether-a-go-go, EAG; EAG-related
      gene, ERG; EAG-like channels, ELK) are important regulators of cellular
      excitability and have key roles in diseases such as cardiac long QT syndrome type
      2 (LQT2), epilepsy, schizophrenia and cancer. The intracellular domains of KCNH
      channels are structurally distinct from other voltage-gated channels. The amino
      terminal region contains an eag domain, which is composed of a Per-Arnt-Sim (PAS)
      domain and a PAS-cap domain, whereas the carboxy-terminal region contains a
      cyclic nucleotide-binding homology domain (CNBHD), which is connected to the pore
      through a C-linker domain. Many disease-causing mutations localize to these
      specialized intracellular domains, which underlie the unique gating and
      regulation of KCNH channels. It has been suggested that the eag domain may
      regulate the channel by interacting with either the S4-S5 linker or the CNBHD.
      Here we present a 2 A resolution crystal structure of the eag domain-CNBHD
      complex of the mouse EAG1 (also known as KCNH1) channel. It displays extensive
      interactions between the eag domain and the CNBHD, indicating that the regulatory
      mechanism of the eag domain primarily involves the CNBHD. Notably, the structure
      reveals that a number of LQT2 mutations at homologous positions in human ERG, in
      addition to cancer-associated mutations in EAG channels, localize to the eag
      domain-CNBHD interface. Furthermore, mutations at the interface produced marked
      effects on channel gating, demonstrating the important physiological role of the
      eag domain-CNBHD interaction. Our structure of the eag domain-CNBHD complex of
      mouse EAG1 provides unique insights into the physiological and pathophysiological
      mechanisms of KCNH channels. 

PMID- 23975099
TI  - Wapl is an essential regulator of chromatin structure and chromosome segregation.
AB  - Mammalian genomes contain several billion base pairs of DNA that are packaged in
      chromatin fibres. At selected gene loci, cohesin complexes have been proposed to
      arrange these fibres into higher-order structures, but how important this
      function is for determining overall chromosome architecture and how the process
      is regulated are not well understood. Using conditional mutagenesis in the mouse,
      here we show that depletion of the cohesin-associated protein Wapl stably locks
      cohesin on DNA, leads to clustering of cohesin in axial structures, and causes
      chromatin condensation in interphase chromosomes. These findings reveal that the
      stability of cohesin-DNA interactions is an important determinant of chromatin
      structure, and indicate that cohesin has an architectural role in interphase
      chromosome territories. Furthermore, we show that regulation of cohesin-DNA
      interactions by Wapl is important for embryonic development, expression of genes
      such as c-myc (also known as Myc), and cell cycle progression. In mitosis, Wapl
      mediated release of cohesin from DNA is essential for proper chromosome
      segregation and protects cohesin from cleavage by the protease separase, thus
      enabling mitotic exit in the presence of functional cohesin complexes. 

PMID- 23975100
TI  - A disinhibitory microcircuit initiates critical-period plasticity in the visual
      cortex.
AB  - Early sensory experience instructs the maturation of neural circuitry in the
      cortex. This has been studied extensively in the primary visual cortex, in which
      loss of vision to one eye permanently degrades cortical responsiveness to that
      eye, a phenomenon known as ocular dominance plasticity (ODP). Cortical inhibition
      mediates this process, but the precise role of specific classes of inhibitory
      neurons in ODP is controversial. Here we report that evoked firing rates of
      binocular excitatory neurons in the primary visual cortex immediately drop by
      half when vision is restricted to one eye, but gradually return to normal over
      the following twenty-four hours, despite the fact that vision remains restricted
      to one eye. This restoration of binocular-like excitatory firing rates after
      monocular deprivation results from a rapid, although transient, reduction in the
      firing rates of fast-spiking, parvalbumin-positive (PV) interneurons, which in
      turn can be attributed to a decrease in local excitatory circuit input onto PV
      interneurons. This reduction in PV-cell-evoked responses after monocular lid
      suture is restricted to the critical period for ODP and appears to be necessary
      for subsequent shifts in excitatory ODP. Pharmacologically enhancing inhibition
      at the time of sight deprivation blocks ODP and, conversely, pharmacogenetic
      reduction of PV cell firing rates can extend the critical period for ODP. These
      findings define the microcircuit changes initiating competitive plasticity during
      critical periods of cortical development. Moreover, they show that the
      restoration of evoked firing rates of layer 2/3 pyramidal neurons by PV-specific
      disinhibition is a key step in the progression of ODP. 

PMID- 23975101
TI  - Social participation in older adults with joint pain and comorbidity; testing the
      measurement properties of the Dutch Keele Assessment of Participation.
AB  - OBJECTIVE: The Keele Assessment of Participation (KAP) questionnaire measures
      person-perceived participation in 11 aspects of life. Participation allows
      fulfilment of valued life activities and social roles, which are important to
      older adults. Since we aimed to use the KAP in a larger Dutch cohort, we examined
      the measurement properties of KAP in a Dutch sample of older adults with joint
      pain and comorbidity. DESIGN: Cohort study. SETTING: A community-based sample in
      Amsterdam, the Netherlands and North Staffordshire, UK. PARTICIPANTS:
      Participants were aged 65 years and over, had at least two chronic diseases
      (identified through general practice consultation) and reported joint pain on
      most days (questionnaire). The Dutch cohort provided baseline data (n=407),
      follow-up data at 6 months (n=364) and test-retest data 2 weeks after 6 months
      (n=122). The UK cohort provided comparable data (n=404). OUTCOME MEASURES: The
      primary outcome was person-perceived participation, as measured with the KAP. The
      measurement properties examined were the following: structural validity (factor
      analysis), internal consistency (Cronbach's alpha), reliability (intraclass
      correlation coefficients; ICC), construct validity (hypothesis testing),
      responsiveness (hypothesis testing and area under the curve) and cross-cultural
      validity (differential item functioning; DIF). RESULTS: Factor analysis revealed
      two domains: KAPd1: 'participation in basic activities' and KAPd2: 'participation
      in complex activities', with Cronbach's alpha of 0.74 and 0.57 and moderate test
      retest reliability: ICC of 0.63 and 0.57, respectively. Further analyses of KAPd1
      showed poor construct validity and responsiveness. Despite the uniform DIF in
      item 'interpersonal relations', the total KAPd1 score seemed comparable between
      the Dutch and UK sample. CONCLUSIONS: Only KAP domain 'participation in basic
      activities' showed good internal consistency and sufficient reliability. KAPd2
      lacks sufficient measurement properties for application in studies, although
      items may be used as single items. Further development of the concept
      'participation' may help the development and validation of instruments to measure
      participation.

PMID- 23975103
TI  - Impact of the economic crisis on children's health in Catalonia: a before-after
      approach.
AB  - OBJECTIVES: To analyse changes in the family living conditions of children in
      Catalonia between 2006 and the 2010-2012 period, and to study associations
      between these changes and health outcomes. DESIGN: A before-after analysis of two
      cross-sectional surveys. SETTING: Population younger than 15 years of age from
      Catalonia, Spain. PARTICIPANTS: Representative samples of children in the 2006
      Catalan Health Survey (ESCA), baseline, before the crisis; n=2200) and the first
      four waves of ESCA 2010-2012 (after start of the crisis, n=1967). MAIN OUTCOME
      MEASURES: Overweight/obesity, health behaviour, mental health and health-related
      quality of life (HRQOL). Logistic regression and multiple linear regression
      models were used to analyse the influence of changes in family conditions on
      outcome measures, including interaction terms to describe the potential influence
      of the study period on the results. RESULTS: The percentage of unemployed
      families rose from 9.1% (2006) to 20.6% (2010-2012), with inequalities by level
      of education. Overweight/obesity increased from 18.4% (95% CI 16.5% to 20.4%) to
      26.9% (24.6% to 29.2%) in 2010-2012, and inequalities related to maternal
      education and employment status persisted. Eating habits have improved in 2010
      2012 in disadvantaged families (ie, junk food consumption improved in families
      with a maternal primary education level; beta (B)=2.85; 0.83 to 4.88, for the
      survey interaction by primary education level). An improvement in HRQOL was found
      in the second survey (B=6.07; 4.15 to 7.99), although children whose mothers had
      a primary education showed poorer HRQOL scores in this survey than in 2006 (B=
      4.14; -7.17 to -1.12). CONCLUSIONS: Although some health-related behaviour
      improved during the study period, childhood obesity increased and inequalities in
      HRQOL appeared. Policy measures that fight against these inequalities should be
      urgently implemented to avoid their negative impact on the health of future
      generations of Catalans.

PMID- 23975102
TI  - Breast milk and cognitive development--the role of confounders: a systematic
      review.
AB  - OBJECTIVES: The association between breastfeeding and child cognitive development
      is conflicted by studies reporting positive and null effects. This relationship
      may be confounded by factors associated with breastfeeding, specifically maternal
      socioeconomic class and IQ. DESIGN: Systematic review of the literature. SETTING
      AND PARTICIPANTS: Any prospective or retrospective study, in any language,
      evaluating the association between breastfeeding and cognitive development using
      a validated method in healthy term infants, children or adults, was included.
      PRIMARY AND SECONDARY OUTCOME MEASURES: Extracted data included the study design,
      target population and sample size, breastfeeding exposure, cognitive development
      assessment tool used and participants' age, summary of the results prior to, and
      following, adjustment for confounders, and all confounders adjusted for. Study
      quality was assessed as well. RESULTS: 84 studies met our inclusion criteria (34
      rated as high quality, 26 moderate and 24 low quality). Critical assessment of
      accepted studies revealed the following associations: 21 null, 28 positive, 18
      null after adjusting for confounders and 17 positive-diminished after adjusting
      for confounders. Directionality of effect did not correlate with study quality;
      however, studies showing a decreased effect after multivariate analysis were of
      superior quality compared with other study groupings (14/17 high quality, 82%).
      Further, studies that showed null or diminished effect after multivariate
      analysis corrected for significantly more confounders (7.7+/-3.4) as compared
      with those that found no change following adjustment (5.6+/-4.5, p=0.04). The
      majority of included studies were carried out during childhood (75%) and set in
      high-income countries (85.5%). CONCLUSIONS: Much of the reported effect of
      breastfeeding on child neurodevelopment is due to confounding. It is unlikely
      that additional work will change the current synthesis. Future studies should
      attempt to rigorously control for all important confounders. Alternatively, study
      designs using sibling cohorts discordant for breastfeeding may yield more robust
      conclusions.

PMID- 23975104
TI  - Facilitating and inhibiting factors for long-term involvement of patients at
      outcome conferences--lessons learnt from a decade of collaboration in OMERACT: a
      qualitative study.
AB  - OBJECTIVE: Several studies have provided insights into the conditions for
      successful patient involvement in health research. We recently demonstrated that
      long-term engagement with people with rheumatic conditions in international
      outcome research led to significant changes in the research agenda in the field
      of rheumatology. This article explores facilitating and inhibiting factors for
      long-term involvement of patients as collaborative partners at five Outcome
      Measures in Rheumatology (OMERACT) conferences. DESIGN: Responsive evaluation,
      starting with a thematic document analysis of conference proceedings and the grey
      literature, followed by 38 qualitative interviews. Interview transcripts were
      subjected to inductive content analysis. SETTING: 5 international OMERACT
      conferences between 2002 and 2012. PARTICIPANTS: Patient delegates (n=16) and
      professional delegates representing researchers (n=14), pharmaceutical industry
      and regulators (n=2). RESULTS: Combined review of the document analysis and
      interview data revealed five main facilitators and three main barriers. Patient
      engagement as full participants at OMERACT conferences was enhanced by: strong
      leadership commitment and the presence of change agents, a clear selection
      procedure, an inclusive consensus-based conference design, individualised and
      self-organised support, an interactive and encouraging moderation style during
      discussion groups. Barriers were related to the intensity of the conference
      programme, scepticism among researchers and doubts about the representativeness
      of the patient group. CONCLUSIONS: This study concludes that developing a
      sustainable structure for funding, selection and support of patient delegates, as
      well as adjusting conference design and moderation style, contributes not only
      towards facilitating direct dialogue between all stakeholders but also towards
      enhancing mutual understanding and the successful incorporation of the patient
      perspective in an outcome conference such as OMERACT.

PMID- 23975105
TI  - Graft-related disease progression in dura mater graft-associated Creutzfeldt
      Jakob disease: a cross-sectional study.
AB  - OBJECTIVES: Details of abnormal prion protein (PrP(Sc)) propagation in the human
      central nervous system (CNS) are unclear. To assess the spread of PrP(Sc) through
      the human CNS, we evaluated dura mater graft-associated Creutzfeldt-Jakob disease
      (dCJD) cases focusing on sites of grafting and dCJD pathological subtypes.
      DESIGN: A cross-sectional study. SETTING: nationwide surveillance data of human
      prion diseases in Japan over the past 12 years were applied for the study.
      PARTICIPANTS: Clinical data were obtained from 84 dCJD patients. OUTCOME
      MEASURES: The clinical courses in cases of dCJD were analysed according to the
      grafting sites (supratentorial and infratentorial groups) and the pathological
      subtypes (non-plaque and plaque types). RESULTS: Of the 84 cases of dCJD in this
      study, 36 (43%) were included in the supratentorial group and 39 (46%) were
      included in the infratentorial group. As initial manifestations, vertigo
      (p=0.007) and diplopia (p=0.041) were significantly more frequent in the
      infratentorial group than in the supratentorial group. During their clinical
      course, cerebellar signs appeared more frequently in the infratentorial group
      than in the supratentorial group (p=0.024). In the non-plaque type cases (n=53),
      the infratentorial group developed vertigo more frequently than the
      supratentorial group (p=0.017); moreover, cerebellar signs appeared more
      frequently in the infratentorial group (p=0.014). However, there was no
      significant difference between groups in the plaque type (n=18). CONCLUSIONS: The
      high frequency of clinical manifestations related to brain stem and cerebellar
      dysfunction in the non-plaque type dCJD with infratentorial grafting suggests
      that PrP(Sc) commonly shows direct propagation into the CNS from contaminated
      dura mater grafts.

PMID- 23975106
TI  - Characteristics associated with requested and required accelerometer wear in
      children.
AB  - OBJECTIVE: To investigate characteristics associated with wearing an
      accelerometer for the required and requested time among 8-year-old to 10-year-old
      children. DESIGN: Cross-sectional. SETTING: 60 Bristol and North Somerset primary
      schools taking part in the 'Active for Life Year 5' randomised controlled trial
      (RCT) in 2011. PARTICIPANTS: 2048 children, aged 8-10 years, invited to wear an
      accelerometer for 5 days of recording. PRIMARY OUTCOME MEASURE: Numbers meeting
      required wear-time for inclusion in main RCT analysis (>=8 h/day >=3 days) and
      numbers meeting requested wear-time (>=8 h/day for all 5 days). RESULTS: 817
      (40%) of the children wore the accelerometer for the requested time and 1629
      (80%) for the required time. In adjusted multivariable analyses the odds of
      wearing the accelerometer for the required time were greater in females as
      compared with males (OR 1.76 (1.42-2.18)), those with higher scores for reporting
      their mother restricted time on sedentary behaviours (1.26 (1.04-1.52) per
      increase of 1 on a 1-4 scale) and in children from schools with larger year group
      sizes (1.01 (1.00-1.02) per additional child). Living in a neighbourhood with
      higher levels of deprivation (0.49 (0.33-0.72) comparing highest to lowest third
      of the deprivation score) or reporting higher levels of weekday outdoor play
      (0.97 (0.94, 1.00) per 30 min more) were associated with reduced odds of meeting
      required time. Results were essentially the same for requested wear-time. Other
      characteristics, including child body mass index, were not associated with
      required or requested wear-time. CONCLUSIONS: Only 40% of children wore the
      accelerometer for the requested time but 80% fulfilled the required criteria to
      be included in the main study analyses. Knowing which characteristics are
      associated with accelerometer wear could help target interventions to increase
      wear-time.

PMID- 23975107
TI  - The role of citizen science in monitoring biodiversity in Ireland.
AB  - Citizen science is proving to be an effective tool in tracking the rapid pace at
      which our environment is changing over large geographic areas. It is becoming
      increasingly popular, in places such as North America and some European
      countries, to engage members of the general public and school pupils in the
      collection of scientific data to support long-term environmental monitoring.
      Participants in such schemes are generally volunteers and are referred to as
      citizen scientists. The Christmas bird count in the US is one of the worlds
      longest running citizen science projects whereby volunteers have been collecting
      data on birds on a specific day since 1900. Similar volunteer networks in Ireland
      have been in existence since the 1960s and were established to monitor the number
      and diversity of birds throughout the country. More recently, initiatives such as
      Greenwave (2006) and Nature Watch (2009) invite school children and members of
      the general public respectively, to record phenology data from a range of common
      species of plant, insect and bird. In addition, the Irish butterfly and bumblebee
      monitoring schemes engage volunteers to record data on sightings of these
      species. The primary purpose of all of these networks is to collect data by which
      to monitor changes in wildlife development and diversity, and in the case of
      Greenwave to involve children in hands-on, inquiry-based science. Together these
      various networks help raise awareness of key environmental issues, such as
      climate change and loss of biodiversity, while at the same time promote
      development of scientific skills among the general population. In addition, they
      provide valuable scientific data by which to track environmental change. Here we
      examine the role of citizen science in monitoring biodiversity in Ireland and
      conclude that some of the data collected in these networks can be used to fulfil
      Ireland's statutory obligations for nature conservation. In addition, a bee
      thought previously to be extinct has been rediscovered and a range expansion of a
      different bee has been confirmed. However, it also became apparent that some of
      the networks play more of an educational than a scientific role. Furthermore, we
      draw on experience from a range of citizen science projects to make
      recommendations on how best to establish new citizen science projects in Ireland
      and strengthen existing ones. 

PMID- 23975108
TI  - Extricating sex and gender in air pollution research: a community-based study on
      cardinal symptoms of exposure.
AB  - This study investigated sex and gender differences in cardinal symptoms of
      exposure to a mixture of ambient pollutants. A cross sectional population-based
      study design was utilized in Sarnia, ON, Canada. Stratified random sampling in
      census tracts of residents aged 18 and over recruited 804 respondents.
      Respondents completed a community health survey of chronic disease, general
      health, and socioeconomic indicators. Residential concentrations of NO2, SO2,
      benzene, toluene, ethylbenzene and o/m/p-xylene were estimated by land use
      regression on data collected through environmental monitoring. Classification and
      Regression Tree (CART) analysis was used to identify variables that interacted
      with sex and cardinal symptoms of exposure, and a series of logistic regression
      models were built to predict the reporting of five or more cardinal symptoms (5+
      CS). Without controlling for confounders, higher pollution ranks increased the
      odds ratio (OR) of reporting 5+ CS by 28% (p < 0.01; Confidence Interval (CI):
      1.07-1.54). Females were 1.52 (p < 0.05; CI: 1.03-2.26) times more likely more
      likely to report 5+ CS after controlling for income, age and chronic diseases.
      The CART analysis showed that allergies and occupational exposure classified the
      sample into the most homogenous groups of males and females. The likelihood of
      reporting 5+ CS among females was higher after stratifying the sample based on
      occupational exposure. However, stratifying by allergic disease resulted in no
      significant sex difference in symptom reporting. The results confirmed previous
      research that found pre-existing health conditions to increase susceptibility to
      ambient air pollution, but additionally indicated that stronger effects on
      females is partly due to autoimmune disorders. Furthermore, gender differences in
      occupational exposure confound the effect size of exposure in studies based on
      residential levels of air pollution.

PMID- 23975109
TI  - Aboriginal and Torres Strait Islander worldviews and cultural safety transforming
      sexual assault service provision for children and young people.
AB  - Child Sexual Assault (CSA) in Aboriginal and Torres Strait Islander communities
      is a complex issue that cannot be understood in isolation from the ongoing
      impacts of colonial invasion, genocide, assimilation, institutionalised racism
      and severe socio-economic deprivation. Service responses to CSA are often
      experienced as racist, culturally, financially and/or geographically
      inaccessible. A two-day forum, National Yarn Up: Sharing the Wisdoms and
      Challenges of Young People and Sexual Abuse, was convened by sexual assault
      services to identify the main practice and policy concerns regarding working with
      Aboriginal and Torres Strait Islander children and young people (C&YP), families
      and communities in the context of CSA. The forum also aimed to explore how
      services can become more accountable and better engaged with the communities they
      are designed to support. The forum was attended by eighty invited Aboriginal and
      Torres Strait Islander and non-Aboriginal youth sexual assault managers and
      workers representing both "victim" and "those who sexually harm others" services.
      In keeping with Aboriginal Community-Based Research methods forum participants
      largely directed discussions and contributed to the analysis of key themes and
      recommendations reported in this article. The need for sexual assault services to
      prioritise cultural safety by meaningfully integrating Aboriginal and Torres
      Strait Islander Worldviews emerged as a key recommendation. It was also
      identified that collaboration between "victims" and "those who sexually harm"
      services are essential given Aboriginal and Torres Strait Islander C&YP who
      sexually harm others may have also been victims of sexual assault or physical
      violence and intergenerational trauma. By working with the whole family and
      community, a collaborative approach is more likely than the current service model
      to develop cultural safety and thus increase the accessibility of sexual assault
      services. 

PMID- 23975111
TI  - Clinical effectiveness of lifestyle management programs: importance of the class
      effect paradox.
AB  - OPINION STATEMENT: It is well appreciated in pharmacotherapy that all drugs
      belonging to the same class of agents are not necessarily equally safe or
      effective. Because of this so-called "class effect paradox," pharmaceutical
      companies must do extensive research to prove the safety and efficacy of a new
      drug before introducing it into the market, even if it belongs to a well
      established class of medications. Like pharmaceutical agents, lifestyle
      management interventions can be organized into classes. This commentary examines
      the rationale for, and importance of, considering the class effect paradox when
      balancing the need for new and innovative lifestyle management programs with the
      need for evidence-based interventions with proven outcomes. In view of the fact
      that all lifestyle management programs within a specific broad intervention class
      do not necessarily result in clinical benefit, it is recommended that any new
      approach should not be widely implemented until it has been shown to be effective
      as evidenced by results of clinical studies published in peer-reviewed journals.

PMID- 23975110
TI  - Intervention and management of congenital left heart obstructive lesions.
AB  - OPINION STATEMENT: While congenital heart defects are typically diagnosed in
      early childhood, depending on the severity of the lesion, they may not be
      recognized until later childhood or in adulthood. Left heart pressure loading
      lesions, including mitral valve stenosis, subaortic stenosis, valvular aortic
      stenosis, supravalvular aortic stenosis, and coarctation of the aorta, may be
      found as an isolated lesion or as a constellation together known as Shone
      syndrome. This review will highlight the literature published regarding the
      diagnosis, intervention, and long-term management of left heart pressure loading
      lesions.

PMID- 23975112
TI  - Cone beam CT analysis of Haller cells: prevalence and clinical significance.
AB  - OBJECTIVES: Haller cells are anterior ethmoid air cells located in the medial
      orbital floor immediately lateral to the maxillary infundibulum. The purpose of
      this study was to demonstrate the prevalence and relationship between the
      existence and size of these cells with ipsilateral maxillary sinusitis and
      orbital floor dehiscence as visualized on cone beam CT (CBCT) images. METHODS:
      CBCT image volumes of 50 patients were retrieved and analysed. All CBCT images
      were acquired with a 9-inch field of view scan. chi(2) and Cochran-Mantel
      Haenszel tests were used for statistical analysis of the obtained data, and p
      values of <0.05 were considered to be statistically significant. RESULTS: There
      was no statistically significant association between the existence and size of
      Haller cells and maxillary sinusitis. There was a significant association between
      Haller cells and orbital floor dehiscence. CONCLUSIONS: The explanation of
      maxillary sinusitis on the basis of mechanical obstruction is unlikely. This
      study provides evidence for the usefulness of CBCT scan in delineation of the
      sinonasal anatomy.

PMID- 23975113
TI  - Non-Hodgkin lymphoma involving the parotid gland: CT and MR imaging findings.
AB  - OBJECTIVES: As an uncommon neoplasm, parotid non-Hodgkin lymphoma (NHL) comprises
      mucosa-associated lymphoid tissue (MALT) and non-MALT lymphomas. Both types of
      lymphoma vary in prognosis and treatment. The aim of this study was to explore CT
      and MRI characteristics of these two types of lymphoma. METHODS: 61 cases of
      parotid NHL, 34 MALT and 27 non-MALT lymphomas with histopathological
      confirmation were examined with routine CT and MR scans prior to treatment, and
      retrospectively reviewed. RESULTS: On CT and MRI, 34 MALT lymphomas presented
      with 11 solid and 23 solid-cystic forms, whereas 27 non-MALT lymphomas presented
      with 25 solid and 2 solid-cystic forms (p < 0.01). CONCLUSIONS: Parotid MALT
      lymphoma is characterized mainly by the solid-cystic form, whereas non-MALT
      lymphoma is characterized mainly by the solid form. The differences on CT and MRI
      can offer helpful information for differentiation of both types of parotid NHL.

PMID- 23975114
TI  - Dynamic MRI of the TMJ under physical load.
AB  - OBJECTIVES: The objective of this study was to examine the kinematics of
      structures of the temporomandibular joint (TMJ) under physiological load while
      masticating. METHODS: Radial MRI was chosen as a fast imaging method to
      dynamically capture the motions of the joint's anatomy. The technique included a
      golden ratio-based increment angle and a sliding window reconstruction. The
      measurements were performed on 22 subjects with and without
      deformation/displacement of the intra-articular disc while they were biting on a
      cooled caramel toffee. RESULTS: The reconstructed dynamic images provided
      sufficient information about the size and localization of the disc as well as the
      change of the intra-articular distance with and without loading. CONCLUSIONS: The
      feasibility of the golden ratio-based radial MRI technique to dynamically capture
      the anatomy of the TMJ under physical load was demonstrated in this initial
      study.

PMID- 23975115
TI  - Differential distribution of sperm subpopulations and incidence of pleiomorphisms
      in ejaculates of captive howling monkeys (Alouatta caraya).
AB  - The aim of this study was to develop an objective method to determine the
      incidence of pleiomorphisms and its influence on the distribution of sperm
      morphometric subpopulations in ejaculates of howling monkeys (Alouatta caraya) by
      using a combination of computerized analysis system (ASMA) and principal
      component analysis (PCA) methods. Ejaculates were collected by electroejaculation
      methods on a regular basis from five individuals maintained under identical
      captive environmental, nutritional, and management conditions. Each sperm head
      was measured for dimensional parameters (Area [A, (square micrometers)],
      Perimeter [P, (micrometers)], Length [L, (micrometers)], and Width [W,
      (micrometers)]) and shape-derived parameters (Ellipticity [(L/W)], Elongation [(L
      - W)/(L + W)], and Rugosity [(4lA/P (2))]). PCA revealed two principal components
      explaining more than the 96 % of the variance. Clustering methods and
      discriminant analyzes were performed and seven separate subpopulations were
      identified. There were differences (P < 0.001) in the distribution of the seven
      subpopulations as well as in the incidence of abnormal pleiomorphisms (58.6 %,
      49.8 %, 35.1 %, 66.4 %, and 55.1 %, P < 0.05) among the five donors tested. Our
      results indicated that differences among individuals related to the incidence of
      pleiomorphisms, and sperm subpopulational structure was not related to the
      captivity conditions or the sperm collection method, since all individuals were
      studied under identical conditions. In conclusion, the combination of ASMA and
      PCA is a useful clinical diagnostic resource for detecting deficiencies in sperm
      morphology and sperm subpopulations in A. caraya ejaculates that could be used in
      ex situ conservation programs of threatened species in Alouatta genus or even
      other endangered neotropical primate species.

PMID- 23975116
TI  - Effects of positive mood on attention broadening for self-related information.
AB  - Studies on cognitive effects of positive emotions have associated positive
      emotions to broadened attention. Given the widely investigated relationship
      between self-focused attention and mood, it is important to investigate the
      effect of positive mood on visuospatial attention for self-related information.
      We used a performance-based measure to assess fluctuations in attentional
      broadening from self-related contrasted to not-self-related information. In
      Experiment 1, we checked that the self-related versus not-self-related stimuli
      did not evoke differential attention effects in general. In Experiment 2, we
      manipulated mood and found that an increase in positive mood was associated with
      a relative broadening of attention for self-related information. These results
      suggest that the meaning of the target of attention provides an interesting
      dimension for further investigation into the relation between positive emotions
      and attentional broadening. 

PMID- 23975117
TI  - Impact of planned movement direction on judgments of visual locations.
AB  - The present study examined if and how the direction of planned hand movements
      affects the perceived direction of visual stimuli. In three experiments
      participants prepared hand movements that deviated regarding direction
      ("Experiment 1" and "2") or distance relative to a visual target position
      ("Experiment 3"). Before actual execution of the movement, the direction of the
      visual stimulus had to be estimated by means of a method of adjustment. The
      perception of stimulus direction was biased away from planned movement direction,
      such that with leftward movements stimuli appeared somewhat more rightward than
      with rightward movements. Control conditions revealed that this effect was
      neither a mere response bias, nor a result of processing or memorizing movement
      cues. Also, shifting the focus of attention toward a cued location in space was
      not sufficient to induce the perceptual bias observed under conditions of
      movement preparation ("Experiment 4"). These results confirm that characteristics
      of planned actions bias visual perception, with the direction of bias (contrast
      or assimilation) possibly depending on the type of the representations
      (categorical or metric) involved. 

PMID- 23975118
TI  - Evidence for multiple strategies in off-beat tapping with anisochronous stimuli.
AB  - There is a large body of evidence relating to the ways that people tap in time
      with sounds, and perform error correction in order to do this. However, off-beat
      tapping is less well investigated than on-beat tapping. The current study
      involves coordinating with a stimulus sequence with underlying isochrony and
      systematic deviations from this isochrony that increase or decrease in magnitude
      to look at people's capacity to error-correct when performing off-beat
      synchronisation with a set of sounds. Participants were instructed to 'tap
      between the tones' but 'try to maintain regularity'. While analysis using typical
      methods suggested a form of error correction was occurring, a series of more
      complex analyses demonstrated that participants' performance during each trial
      can be classified according to one of four different strategies: maintaining a
      regular pulse, error correction, phase resetting, and negative error correction.
      While maintaining a regular pulse was the preferred strategy in conditions with
      increasingly isochronous stimuli, the majority of trials are best explained by
      other strategies, suggesting that participants were generally influenced by
      variability in the stimuli. 

PMID- 23975119
TI  - Interventional three-year longitudinal study of melanocytic naevus development in
      pre-school children in Dresden, Saxony.
AB  - Acquired melanocytic naevi (MN) are considered a risk factor for melanoma.
      Exposure to ultraviolet light (UV) is the major environmental factor for MN. UV
      protection is most critical in pre-school children. This 3-year interventional
      longitudinal study examined 395 3-year-old children attending daycare centres
      (DCC) in Dresden, Germany. Photo-skin type, eye and hair colour were recorded.
      DCC were randomly assigned to a control group and a behavioural intervention
      group. All children had a regular naevus check-up, including digital objective
      analysis with Dell'Eva-Burroni Dermoscopy Melanoma Image Processing Software (DB
      MIPS) technology. Parents of children in the intervention group received
      additional guidance for sun-protection. The mean total MN counts of both groups
      at the start of the study period were 7.19 +/- 4.55 (intervention) and 6.84 +/-
      4.63 (control), respectively. There was a significant increase in MN counts for
      both groups (mean 12.5 and 13.8). Subgroup analysis for skin type, eye colour,
      and hair colour did not demonstrate a significant influence on MN counts. The DB
      MIPS integrated classifier revealed no risky lesions while analysing their
      patterns. Intervention did not reduce the number of newly acquired MN. MN counts
      in pre-school children were approximately 5 times higher than expected from
      previous large studies in Germany. This is the first study in pre-school children
      using objective digital image analysis of pigmented lesions. No atypical lesions
      were observed. New approaches to UV protection in pre-school children are now
      required. 

PMID- 23975120
TI  - A brief overview of factors affecting speech intelligibility of people with
      hearing loss: implications for amplification.
AB  - PURPOSE: The authors aimed to determine the predictability of speech
      intelligibility of people with different degrees of hearing loss from audibility
      and other factors. METHOD: After a brief overview of why people with hearing loss
      have greater difficulty in understanding speech than people with normal hearing,
      the authors describe a study that was aimed to predict speech intelligibility
      from audibility, psychoacoustic abilities, cognitive ability, and age. RESULTS:
      The study showed that the ability of people with hearing loss to extract speech
      information from an audible signal decreased with increase in hearing loss. This
      hearing loss desensitization was significantly related to hearing thresholds,
      sharpness of psychophysical tuning curves, presence of dead regions, age, and
      cognitive ability. After allowing for the effects of hearing loss, the authors
      found that speech intelligibility was significantly related to age and cognitive
      ability. The effects did not vary with frequency. CONCLUSIONS: The current
      evidence supports the allowance of hearing loss desensitization in prescribing
      amplification that is aimed to maximize speech intelligibility. There is
      insufficient evidence to recommend the inclusion of estimates of frequency
      resolution or dead regions in prescribing amplification.

PMID- 23975121
TI  - Introduction to the AJA research forum on aging and hearing: mechanisms and
      effects.
AB  - PURPOSE This Research Forum, "Aging and Hearing: Mechanisms and Effects,"
      highlights 6 contributions presented at the 2nd International Conference on Adult
      Hearing Screening (AHS 2012), held in Cernobbio (Lake Como, Italy) in June 2012.
      Overall, the articles in this Research Forum give insight into the causes,
      mechanisms, and consequences of auditory dysfunctions in adults, with particular
      focus on their implications for screening, assessment, and intervention. 

PMID- 23975122
TI  - Understanding the speech-understanding problems of older adults.
AB  - PURPOSE: The purpose of this article was to review recent research from our
      laboratory on the speech-understanding problems of older adults. METHOD: The
      method involved a narrative review of previously reported data from our
      laboratory. CONCLUSION: To date, the results from most of our studies have
      indicated that peripheral and cognitive factors are the primary contributors to
      the speech-understanding problems of older adults, with the relative mix of these
      2 factors changing for unaided (primarily peripheral) and aided (primarily
      cognitive) listening conditions.

PMID- 23975123
TI  - Introduction to the AJA research forum on intervention and rehabilitation
      strategies for adults and older adults.
AB  - PURPOSE To give an overview of the third in a series of research forums emerged
      from the second International Conference on Adult Hearing Screening (AHS 2012),
      which was held in Cernobbio (Lake Como, Italy) in June 2012. The first two
      research forums, published in the previous and current issues of this journal,
      included several key contributions from the AHS meeting in 2 major topic areas,
      "Hearing Screening in Adults and Older Adults" (Vol. 22, June 2013) and "Aging
      and Hearing: Mechanisms and Effects" (this issue). In the 7 articles showcased in
      this Research Forum on "Intervention and Rehabilitation Strategies for Adults and
      Older Adults," the authors provide a multifaceted view on recent advancements in
      intervention strategies for adults with hearing loss, with ample emphasis on
      auditory training; discuss the research challenges that need to be tackled in
      this field; and explore new ways to take into account the individual needs and
      obtain a deeper understanding of the peculiar attributes of hearing in older
      adults. 

PMID- 23975124
TI  - Age-dependent changes in temporal-fine-structure processing in the absence of
      peripheral hearing loss.
AB  - PURPOSE: In this study, the author sought to investigate if and when the ability
      to process temporal-fine-structure (TFS) cues deteriorates with age in adults
      with audiometrically normal hearing sensitivity. METHOD: Using a cross-sectional
      design, the author assessed TFS sensitivity in 102 normal-hearing adults sampled
      from across the entire range of adulthood (ages 18-90 years), using 2
      psychophysical tests for the assessment of within- and across-ear TFS processing.
      RESULTS: Both types of TFS sensitivity (monaural and binaural) declined gradually
      starting in young adulthood, with the earliest significant deficit already
      apparent in early midlife (i.e., between ages 40 and 49 years). TFS sensitivity
      was not correlated with absolute sensitivity at the test frequency. CONCLUSIONS:
      Some suprathreshold auditory processing abilities decline throughout adulthood,
      even when an individual's peripheral hearing is clinically normal. These deficits
      are not captured by a conventional, audiometric hearing assessment but may
      contribute to the increasing difficulties with age to identify speech in noisy
      environments. From a methodological point of view, the existence of such age
      effects warrants the use of age-matched participant groups when comparing normal
      and impaired peripheral hearing.

PMID- 23975125
TI  - Evidence-based practice in audiology: rehabilitation options for adults with
      hearing impairment.
AB  - PURPOSE: The authors address 3 questions: (a) What is evidence-based practice
      (EBP), and why is it important for adults with hearing impairment? (b) What is
      the evidence about intervention options for adults who fail a hearing screening
      and are identified with hearing impairment? (c) What intervention options do
      adults choose when identified with hearing impairment for the first time? METHOD:
      The 5 steps of the EBP process are discussed in relation to a clinical question
      about whether hearing aids and communication programs reduce activity limitations
      and participation restrictions compared with no treatment for adults who fail a
      hearing screening and are identified with hearing impairment. RESULTS: Systematic
      reviews of the evidence indicate that both hearing aids and communication
      programs reduce activity limitations and participation restrictions for this
      population and are therefore appropriate options. A study is then described in
      which these options were presented to 153 clients identified with hearing
      impairment for the first time: 43% chose hearing aids, 18% chose communication
      programs, and the remaining 39% chose not to take any action. CONCLUSION: EBP
      supports the offer of intervention options to adults who fail a hearing screening
      and are identified with hearing impairment.

PMID- 23975126
TI  - Benefits of auditory training for aided listening by older adults.
AB  - PURPOSE: In this article, the authors provide an overview of auditory training
      programs for aided listening by older adults, review criteria for evaluating
      effectiveness, summarize results of published studies, report on 2 training
      programs currently undergoing assessment, and discuss directions and needs for
      future research. METHOD: Experiments are ongoing to evaluate 2 individual,
      computer-based speech-perception training programs: Indiana University (IU) word
      based training and the Speech Perception Assessment and Training System (SPATS).
      Training and control subjects are older adults with mild-to-severe hearing loss.
      Subjects train for about 30 hr with monaurally presented, spectrally shaped
      stimuli (IU) or through loudspeakers with their own hearing aids (SPATS).
      Displays and feedback use auditory and visual/orthographic cues. Outcome measures
      include objective measures of speech recognition in noise and other training
      benefits. RESULTS: Significant improvements were observed in open-set recognition
      of trained sounds, words, phrases, and sentences. Large individual differences in
      training benefit were apparent. Generalization varied with the speech-perception
      task, competing noise, listening strategy, and pretraining scores. CONCLUSIONS:
      High-level evidence is needed to support the effectiveness of auditory training
      for older adults as a supplement to aided listening. Studies are needed to
      predict who will benefit from specific types of training, to assess compliance
      and engagement, and to discover benefits beyond communication.

PMID- 23975127
TI  - A new web-based tool for group audiologic rehabilitation.
AB  - PURPOSE: The Group Rehabilitation Online Utility Pack (GROUP) was developed to
      encourage hearing health care professionals to offer group audiologic
      rehabilitation (GAR) as an integral part of adult hearing rehabilitation and to
      provide these professionals with the necessary tools to develop and offer GAR in
      their clinical practice. METHOD: The GROUP is a dynamic interactive web-based
      program that allows visitors to craft and create GAR for their professional use.
      The tool includes the evidence for implementing GAR, content for preparation and
      planning, instruction for facilitating groups, and actual GAR activities. Each
      section includes ethnographic videos, allowing professionals to observe GAR in
      action. CONCLUSION: The GROUP program available on the Ida Institute website was
      developed with the intent to provide clinicians, academicians, researchers, and
      students a resource to facilitate the development and implementation of GAR
      programs throughout the world.

PMID- 23975128
TI  - Edible bird's nest: food or medicine?
AB  - Edible bird's nest (EBN) is derived from the saliva of certain types of
      swiftlets. It is consumed in many parts of the world for its nutritional and
      medicinal values. Although many claims have been made on the therapeutic and
      health-promoting effects of EBN, scientific documentations regarding these
      effects are very limited in published literature. It is not until recently that
      the biological effects of EBN are being investigated and evidence-based studies
      are being conducted. Several studies have found that EBN may enhance cell
      proliferation and differentiation and various beneficial effects have been
      reported in vitro as well as in vivo. While these studies point towards the
      potential use of EBN in the treatment or even prevention of several diseases, the
      mechanisms of action of EBN remain largely unknown and more explorations are
      needed. This review is one of the very few scientific reviews on EBN which
      focuses on recent evidence-based discoveries.

PMID- 23975129
TI  - Cross-sectional survey on complementary and alternative medicine awareness among
      health care professionals and students using CHBQ questionnaire in a Balkan
      country.
AB  - OBJECTIVE: To conduct a study on attitudes, knowledge, and use of complementary
      and alternative medicine (CAM) therapies in Serbia. Available data about CAM
      therapies in the region are scarce, opinions lacking from health sector. Balkan
      region countries had a delay in issuing national policies on CAM therapies.
      METHODS: The questionnaire used was based on previously validated CAM Health
      Belief Questionnaire (CHBQ), formulated as 5-item Likert type scale, adjusted for
      local environment. Health care students and professionals were evaluated. The
      questionnaire comprehended 10 closed questions on attitudes, knowledge and use of
      CAM therapies. This survey was conducted in eight cities of Serbia, January 2010
      July 2011. A total of 797 participants was included. The second group of
      participants was 145 healthcare professionals (50 academic staff, 64 clinical
      staff, 19 pharmacists, 6 other clinical branch specialists and 6 nurses). Data
      were collected by an interview. Examinees could acquire maximum of 70 points, 35
      representing neutral attitude. RESULTS: Students of dentistry (54.65+/-6.07) were
      better informed on CAM therapies than medicine students (50.26+/-7.92). Pharmacy
      students (51.16+/-7.10) accepted low-scientific CAM. Pharmacists scored better
      than university professors (55.12+/-6.55 vs. 50.29+/-9.50). Primary health care
      professionals had better awareness than pharmacists in dispensing pharmacies.
      Both groups of participants preferred use of vitamins over any other CAM therapy.
      CONCLUSION: These pioneering efforts in the region exposed weaknesses in CAM
      attitudes of current and future health care professionals. Nevertheless,
      awareness on alternative medicine treatment choices is growing among Balkan
      prescribers. Supportive legal framework would facilitate dissemination of CAM
      medical practices.

PMID- 23975130
TI  - Study on the networks of "Nature-Family-Component" of Chinese medicinal herbs
      based on association rules mining.
AB  - OBJECTIVE: To explore appropriate methods for the research of the theory of
      Chinese medicine nature property and find the relationship between Nature-Family
      Component of Chinese herbs. METHODS: From perspective of systems biology, we used
      Associate Network to identify useful relationships among "Nature-Family
      Component" of Herbs. In this work, Associate Network combines association rules
      mining method and network construction method to evaluate the complicate
      relationship among "Nature-Family-Component" of herbs screened. RESULTS: The
      results of association rules mining showed that the families had a close
      relationship with nature properties of herbs. For example, the families of
      Magnoliaceae, Araceae had a close relationship with hot nature with confidence of
      100%, the families of Cucurbitaceae has a close relationship to cold nature with
      confidence of 90.91%. Moreover, the results of constructed Associate Network
      implied that herbs belonging to the same families generally had the same natures.
      In addition, some herbs belonging to different families may also have same
      natures when they contain the same main components. CONCLUSION: These results
      implied that the main components of herbs might affect their natures; the
      relationships between families and natures were based on the main compounds of
      herbs.

PMID- 23975131
TI  - Jiaotai Pill enhances insulin signaling through phosphatidylinositol 3-kinase
      pathway in skeletal muscle of diabetic rats.
AB  - OBJECTIVE: To investigate the effect of Jiaotai Pill (, JTP) at different
      constitutional proportions on insulin signaling through phosphatidylinositol 3
      kinase (PI3K) pathway in the skeletal muscle of diabetic rats. METHODS: The rat
      model of type 2 diabetes mellitus (T2DM) was established by intravenous injection
      of a small dose of streptozotoein plus high fat diet feeding. JTP at the same
      dosage of cinnamon and the increasing dosage of Coptis chinensis was administered
      to diabetic rats for nine weeks respectively. Plasma glucose and insulin levels
      were assayed. The expressions of proteins were determined by Western blot method.
      RESULTS: All the three formulations of JTP decreased plasma glucose and fasting
      insulin levels as well as increased the protein expressions of insulin receptor
      beta (InsRbeta) subunit, insulin receptor substrate-1 (IRS-1), PI3K p85 subunit
      and glucose transporter 4 (GLUT4) in skeletal muscle. Meanwhile, JTP increased
      the tyrosine phosphorylation of InsRbeta subunit and IRS-1, and reduced the
      serine phosphorylation of IRS-1 in skeletal muscle. Interestingly, the effect of
      JTP on improving insulin sensitivity was not dose-dependent. In contrast, JTP
      containing the least amount of Coptis chinensis exhibited the best effect.
      CONCLUSION: JTP at different constitutional proportions attenuates the
      development of diabetes in a rat model of T2DM. The mechanism might be associated
      with enhancing insulin signaling through PI3K pathway in the skeletal muscle.

PMID- 23975132
TI  - Effect of Xuebijing injection on systemic lupus erythematosus in mice.
AB  - OBJECTIVE: To observe the effects of Xuebijing injection on dendritic cells (DCs)
      and T lymphocytes, and the potential mechanisms of its therapeutic effect on
      systemic lupus erythematosus (SLE). METHODS: A widely used mouse model, SLE-prone
      BLLF1 mice aged 8-10 weeks, was employed. Mice were randomly divided into 4
      groups: a normal group, a model group and two treatment groups treated with
      Xuebijing Injection with a dose of 6.4 mL/kg via intraperitoneal administration
      for SLE-prone BLLF1 mice aged 8 weeks (treatment A group) and 10 weeks (treatment
      B group). Renal tissue sections were stained with Masson's trichrome and periodic
      acid-silver methenamine. Histopathological changes in the kidney were evaluated
      by a light microscopy. The capacity of the DCs isolated from the spleen to
      stimulate the T cell proliferation in response to concanavalin A (Con A) was
      determined. RESULTS: Compared with the model group, levels of anti-dsDNA
      antibodies in the two treatment groups decreased remarkablly (P<0.01, P<0.05),
      and levels of serum creatinine and blood urea nitrogen increased (P<0.01,
      P<0.05). Pathological changes were found in the kidney in the model group.
      Histopathological abnormalities were alleviated in the two treatment groups.
      Treatment with Xuebijing injection also significantly upregulated the expression
      of CD80, CD86 and major histocompatibility class II by DCs compared with the
      model group (P<0.05). When splenic T lymphocytes from BLLF1 mice were co-cultured
      with DCs at ratios of 1:100, 1:150 and 1:200 for 3 and 5 days, the proliferation
      of T lymphocytes was suppressed compared with the normal group (P<0.05), but this
      was restored by Xuebijing Injection under the same conditions. In the model
      group, levels of tumor necrosis factor (TNF)-alpha in supernatants were
      significantly elevated compared with the normal group (P<0.01), interleukin-2
      levels decreased (P<0.05), while these changes were significantly alleviated in
      the Xuebijing treatment groups. CONCLUSIONS: Xuebijing Injection alleviated renal
      injury in SLE-prone BLLF-1 mice. The mechanism might be through influencing T
      cell polarization mediated by DCs, and Xuebijing Injection might be a potential
      drug that suppresses immune dysfunction in patients with SLE.

PMID- 23975133
TI  - Qindan capsule changes adventitial collagen synthesis in spontaneously
      hypertensive rats.
AB  - OBJECTIVE: To investigate the effect of Qindan capsule (QC) on collagen synthesis
      and the mechanism underlying the process in spontaneously hypertensive rats
      (SHRs). METHODS: Twentyfour SHRs were divided into three groups: the hypertension
      model group, the QC treatment group, and the losartan treatment group. Eight
      Wistar Kyoto (WKY) rats were used as the normal control group. The systolic blood
      pressure (SBP) of the rats was monitored, and the thoracic aorta adventitia of
      the rats was segregated. The expressions of transforming growth factor 1 (TGF
      beta1), Smad3, and collagens I and were measured by histological staining and
      reverse transcription polymerase chain reaction. RESULTS: The SBP was
      significantly higher in the model group than in the normal control group
      (P<0.01). However, a significant SBP-lowering effect was observed in QC or
      losartan treatment groups (P<0.05 or P<0.01) after 3 weeks of treatment. QC
      treated rats showed a decrease of approximately 40 mm Hg, and the losartan
      treated rats showed a decrease of approximately 50 mm Hg at the end of treatment
      compared with the beginning of treatment. The protein and gene levels of TGF
      beta1, Smad3, and collagens I and in the model group were significantly increased
      compared with those in the normal control group (P<0.01). However, the levels
      were significantly decreased in the QC or losartan treatment group compared with
      the model group (P<0.05 or P<0.01). However, there was no significant difference
      between the QC and losartan treatment groups (P<0.05). CONCLUSIONS: QC could
      exert its antihypertensive effect through down-regulating TGF-beta1-stimulated
      collagen expressions. The TGF-beta1/Smad3 signaling pathway may be involved in
      this process.

PMID- 23975134
TI  - Effect of Chinese herbal medicine for nourishing yin, supplementing qi, and
      activating blood on the Th1/Th2 immune balance in peripheral blood in patients
      with primary Sjogren's syndrome.
AB  - OBJECTIVE: To observe the effect of Chinese herbal medicine for nourishing yin,
      supplementing qi, and activating blood on the expression of interferon-gamma (IFN
      gamma)/interleukin-4 (IL-4) in peripheral blood and disease activity in primary
      Sjogren's syndrome (pSS) patients, and to study the relationship between the
      immune balance of Th1/Th2 and the disease activity. METHODS: A total of 66 pSS
      patients were randomized with tossing coins method into two groups: the
      integrative therapy group (34 cases) and the control group (32 cases); and 28
      healthy subjects were taken as the normal group. The integrative therapy group
      was treated by Chinese herbal medicines for nourishing yin, supplementing qi, and
      activating blood combined with hydroxychloroquine sulfate tablets and the control
      group was treated with hydroxychloroquine sulfate tablets. The treatment course
      was 3 months for both groups. The levels of serum immunoglobulin G (IgG),
      erythrocyte sedimentation rate (ESR), IFN-gamma and IL-4 in peripheral blood were
      measured before and after treatment. RESULTS: Compared with the normal group, the
      levels of IgG, ESR, IFN-gamma and IL-4 were significantly increased in pSS
      patients (P<0.05). Remarkably, after 3 months of treatment, these levels were
      dramatically decreased in both the integrative therapy group and the control
      group, although still higher than the normal group. The levels of IgG, ESR, IFN
      gamma and IL-4 in the integrative therapy group were lower than the control group
      and the same group before treatment (P<0.05). The ratio of IFN-gamma/IL-4 also
      significantly decreased after treatment. Moreover, the level of IFN-gamma and the
      ratio of IFN-gamma/IL-4 in the integrative therapy group were significantly lower
      than the control group (P<0.05). For all patients the ratio of IFN-gamma/IL-4
      before and after treatment was positive correlated with the levels of IgG and
      ESR. CONCLUSION: Chinese herbal medicine for nourishing yin, supplementing qi,
      and activating blood can alleviate the disease activity of pSS by regulating the
      immune balance of Th1/Th2.

PMID- 23975135
TI  - Relationship between endogenous hydrogen sulfide and blood stasis syndrome based
      on the Qi-blood theory of Chinese medicine.
AB  - "Qi" and "blood" are two essential concepts in Chinese medicine (CM). As qi is
      intangible, the concept of qi is still controversial between CM and Western
      medicine. However, the endogenous hydrogen sulfide (H2S) and other gaseous
      signaling molecules provides a new approach for understanding the essence of qi
      in CM. Blood stasis syndrome is a common syndrome in CM. According to the CM
      theory, the incidence of blood stasis syndrome is closely correlated to the
      reckless movement of qi, as qi and blood are inseparable in regulating
      physiological functions. In recent years, more and more evidences suggest a close
      correlation between blood stasis syndrome and microcirculation dysfunction. In
      this paper, we discuss the relationship between endogenous H2S and blood stasis
      syndrome based on qi-blood theory of CM. We found that endogenous H2S maybe a
      material basis in concept of qi in CM, while dysfunctional microcirculation is
      the pathological basis of the blood stasis syndrome. As qi is closely associated
      with incidence and progression of blood stasis syndrome, endogenous H2S may play
      an important role in preventing and treating the blood stasis syndrome by
      improving the function of microcirculation. 

PMID- 23975136
TI  - Differences in the origin of philosophy between Chinese medicine and Western
      medicine: Exploration of the holistic advantages of Chinese medicine.
AB  - To explore advantages of Chinese medicine (CM) by analyzing differences in the
      origin of philosophy for human health between CM and Western medicine (WM).
      Methodologically, a distinctive feature of CM is its systems theory, which is
      also the difference between CM and WM. Since the birth of CM, it has taken the
      human body as a whole from the key concepts of "qi, blood, yin-yang, viscera
      (Zang-Fu), and meridian and channel", rather than a single cell or a particular
      organ. WM evolves from the Western philosophic way of thinking and merely uses
      natural sciences as the foundation. The development of WM is based on human
      structures, or anatomy, and therefore, research of WM is also based on the way of
      thinking of decomposing the whole human body into several independent parts,
      which is the impetus of promoting the development of WM. The core of CM includes
      the holistic view and the dialectical view. Chinese herbal medicines contain
      various components and treat a disease from multiple targets and links.
      Therefore, Chinese herbal medicines treat a diseased state by regulating and
      mobilizing the whole body rather than just regulating a single factor, since the
      diseased state is not only a problem in a local part of the body but a local
      reflection of imbalance of the whole body. 

PMID- 23975137
TI  - Acetaminophen-induced acute liver failure cured by integrative therapy of Chinese
      and Western medicine--a case report.

PMID- 23975138
TI  - Therapeutic effects of Shenfu Injection on post-cardiac arrest syndrome.
AB  - Survival rates after cardiac arrest have not changed substantially over the past
      5 decades. Postcardiac arrest (CA) syndrome (PCAS) is the primary reason for the
      high mortality rate after successful restoration of spontaneous circulation
      (ROSC). Intravenous administration of Shenfu Injection (, SFI) may attenuate post
      CA myocardial dysfunction and cerebral injury, inhibit systemic
      ischemia/reperfusion responses, and treat underlying diseases. In this article,
      we reviewed the therapeutic effects of SFI in PCAS. SFI might be useful in the
      treatment of PCAS, incorporating the multi-link and multi-target advantages of
      Chinese medicine into PCAS management. Further experimental and clinical research
      to verify the therapeutic effects of SFI in PCAS is required. 

PMID- 23975139
TI  - DMSO enhances electrospray response, boosting sensitivity of proteomic
      experiments.
AB  - We report that low percentages of dimethylsulfoxide (DMSO) in liquid
      chromatography solvents lead to a strong enhancement of electrospray ionization
      of peptides, improving the sensitivity of protein identification in bottom-up
      proteomics by up to tenfold. The method can be easily implemented on any LC-MS/MS
      system without modification to hardware or software and at no additional cost. 

PMID- 23975140
TI  - DeNovoGear: de novo indel and point mutation discovery and phasing.
AB  - We present DeNovoGear software for analyzing de novo mutations from familial and
      somatic tissue sequencing data. DeNovoGear uses likelihood-based error modeling
      to reduce the false positive rate of mutation discovery in exome analysis and
      fragment information to identify the parental origin of germ-line mutations. We
      used DeNovoGear on human whole-genome sequencing data to produce a set of
      predicted de novo insertion and/or deletion (indel) mutations with a 95%
      validation rate. 

PMID- 23975141
TI  - Silicon nanowire-silver indium selenide heterojunction photodiodes.
AB  - Structural and optoelectronic properties of silicon (Si) nanowire-silver indium
      selenide (AgInSe2) thin film heterojunctions were investigated. The metal
      assisted etching method was employed to fabricate vertically aligned Si nanowire
      arrays. Stoichiometric AgInSe2 films were then deposited onto the nanowires using
      co-sputtering and sequential selenization techniques. It was demonstrated that
      the three-dimensional interface between the Si nanowire arrays and the AgInSe2
      thin film significantly improved the photosensitivity of the heterojunction diode
      compared to the planar reference. The improvements in device performance are
      discussed in terms of interface state density, reflective losses and surface
      recombination of the photogenerated carriers, especially in the high-energy
      region of the spectrum. 

PMID- 23975142
TI  - beta-Trace protein and prognosis in patients with atrial fibrillation receiving
      anticoagulation treatment.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with a high risk of mortality
      and morbidity and it commonly coexists with chronic kidney disease. A biomarker
      of renal function, beta-trace protein (BTP), has been implicated in the
      progression of cardiovascular disease. The aim of our study was to evaluate the
      association of BTP with adverse cardiovascular events, bleeding, and mortality in
      patients with AF. METHODS: In a consecutive cohort of patients with nonvalvular
      AF receiving anticoagulation treatment, plasma BTP was determined using an
      automated nephelometer BN ProSpec System (Siemens) and related to estimated
      glomerular filtration rate (eGFR). We recorded adverse cardiovascular events
      (stroke, acute coronary syndrome, and acute pulmonary edema), major bleeding, and
      mortality. RESULTS: We included 1,279 patients (48.6% men), aged 76 years (IQR,
      71-81 years), who were followed up for 996 days (IQR, 802-1,254 days). During the
      follow-up, there were 150 cardiovascular events (annual rate, 3.99%), 57
      embolisms (annual rate, 1.54%), and 114 major bleeding events (annual rate,
      3.04%), and 161 patients died (annual rate, 4.32%). BTP levels were inversely
      associated with eGFR (P < .001). High BTP concentrations were significantly
      associated with embolic events (hazard ratio [HR], 4.64 [1.98-10.86]; P < .001),
      composite adverse cardiovascular events (HR, 1.93 [1.31-2.85]; P = .001), and
      mortality (HR, 2.08 [1.49-2.90]; P < .001), even after adjusting for CHAD2DS2
      VASc (congestive heart failure, hypertension, age >= 75 years [doubled], diabetes
      mellitus, stroke [doubled], vascular disease, age 65 to 74 years, sex category)
      score and renal function. High BTP was associated with major bleeding events (HR,
      1.88 [1.18-3.00]; P = .008), even after adjusting for the HAS-BLED (hypertension,
      abnormal renal/liver function, stroke, bleeding history or redisposition, labile
      international normalized ratio, elderly [> 65 years], drugs/alcohol
      concomitantly) score. CONCLUSIONS: We suggest that BTP, a proposed renal damage
      biomarker, may be a novel predictor of adverse cardiovascular events, major
      bleeding, and mortality in patients with AF. BTP may help refine clinical risk
      stratification in these patients.

PMID- 23975143
TI  - Thymosin beta4 and tissue transglutaminase. Molecular characterization of cyclic
      thymosin beta4.
AB  - Thymosin beta4 is the prototype of beta-thymosins and is present in almost every
      mammalian cell. It is regarded to be the main intracellular G-actin sequestering
      peptide. Thymosin beta4 serves as a specific glutaminyl substrate for guinea pig
      transglutaminase. In the absence of an appropriate additional aminyl donor an
      epsilon-amino group of thymosin beta4 serves also as an aminyl substrate and an
      intramolecular bond is formed concomitantly NH3 (17 Da) is lost. The molecular
      mass of the product is 4,949.6 Da. This is 16.3 Da less than the molecular mass
      of thymosin beta4 (4,965.9 Da). Digestion with endopeptidases and Edman
      degradation of the fragments identified the exact position of the ring forming
      isopeptide bond. In spite of 3 glutaminyl and 9 lysyl residues of thymosin beta4
      only one isopeptide bond between Lys16 and Gln36 was formed (cyclic thymosin
      beta4). These two amino acid residues are conserved in all beta-thymosins. Cyclic
      thymosin beta4 still forms a complex with G-actin albeit the stability of the
      complex is about one fiftieth of the stability of the thymosin beta4 * G-actin
      complex.

PMID- 23975144
TI  - Interaction of human serum albumin with novel 3,9-disubstituted perylenes.
AB  - Human serum albumin (HSA) has been used as a model for the binding of a number of
      different ligands, including polyaromatic hydrocarbons, to proteins. In this case
      we have investigated the interaction of HSA with a novel set of perylene
      derivatives. Di-substituted perylene analogues have been synthesized as
      potentially useful organic photovoltaic materials. Their photophysical properties
      may make them viable for fuel cell applications too. However, these molecules are
      poorly soluble especially in aqueous solvents. Binding to water-soluble proteins
      may provide a way to solubilize them. At the same time one can study whether the
      photophysical processes initiated by the irradiation of a perylene ligand can
      cause conformational changes to the host protein. With the present study we
      demonstrated that of the three perylene derivatives investigated only one, the
      dimethoxy analogue, has a significant affinity for HSA at a binding site near the
      bottom of the central cleft (in proximity of the Trp214 residue). The small
      affinity prevents any significant photoinduced changes to occur in the protein. 

PMID- 23975145
TI  - Guidelines and best practices for electrophysiological data collection, analysis
      and reporting in autism.
AB  - The EEG reflects the activation of large populations of neurons that act in
      synchrony and propagate to the scalp surface. This activity reflects both the
      brain's background electrical activity and when the brain is being challenged by
      a task. Despite strong theoretical and methodological arguments for the use of
      EEG in understanding the neural correlates of autism, the practice of collecting,
      processing and evaluating EEG data is complex. Scientists should take into
      consideration both the nature of development in autism given the life-long,
      pervasive course of the disorder and the disability of altered or atypical
      social, communicative, and motor behaviors, all of which require accommodations
      to traditional EEG environments and paradigms. This paper presents guidelines for
      the recording, analyzing, and interpreting of EEG data with participants with
      autism. The goal is to articulate a set of scientific standards as well as
      methodological considerations that will increase the general field's
      understanding of EEG methods, provide support for collaborative projects, and
      contribute to the evaluation of results and conclusions. 

PMID- 23975146
TI  - MicroRNA mediated regulation of metal toxicity in plants: present status and
      future perspectives.
AB  - The human population is increasing at an alarming rate, whereas heavy metals
      (HMs) pollution is mounting serious environmental problem, which could lead to
      serious concern about the future sufficiency of global food production. Some HMs
      such as Mn, Cu, and Fe, at lower concentration serves as an essential vital
      component of plant cell as they are crucial in various enzyme catalyzed
      biochemical reactions. At higher concentration, a vast variety of HMs such as Mn,
      Cu, Cd, Fe, Hg, Al and As, impose toxic reaction in the plant system which
      greatly affect the crop yield. Recently, microRNAs (miRNAs) that are small class
      of non-coding riboregulator have emerged as central regulator of numerous abiotic
      stresses including HMs. Increasing reports indicate that plants have evolved
      specialized inbuilt mechanism viz. signal transduction, translocation and
      sequestration to counteract the toxic response of HMs. Combining computational
      and wet laboratory approaches have produced sufficient evidences concerning
      active involvement of miRNAs during HMs toxicity response by regulating various
      transcription factors and protein coding genes involved in plant growth and
      development. However, the direct role of miRNA in controlling various signaling
      molecules, transporters and chelating agents of HM metabolism is poorly
      understood. This review focuses on the latest progress made in the area of direct
      involvement of miRNAs in signaling, translocation and sequestration as well as
      recently added miRNAs in response to different HMs in plants. 

PMID- 23975148
TI  - [Cost efficiency analysis of CT coronary angiography for exclusion of significant
      coronary artery stenosis: comparison with conventional invasive coronary
      angiography before cardiac surgery].

PMID- 23975147
TI  - Coexpression network analysis associated with call of rice seedlings for
      encountering heat stress.
AB  - Coexpression network analysis is useful tool for identification of functional
      association of coexpressed genes. We developed a coexpression network of rice
      from heat stress transcriptome data. Global transcriptome of rice leaf tissues
      was performed by microarray at three time points--post 10 and 60 min heat stress
      at 42  degrees C and 30 min recovery at 26  degrees C following 60 min 42 
      degrees C heat stress to investigate specifically the early events in the heat
      stress and recovery response. The transcriptome profile was significantly
      modulated within 10 min of heat stress. Strikingly, the number of up-regulated
      genes was higher than the number of down-regulated genes in 10 min of heat
      stress. The enrichment of GO terms protein kinase activity/protein serine
      threonine kinase activity, response to heat and reactive oxygen species in up
      regulated genes after 10 min signifies the role of signal transduction events and
      reactive oxygen species during early heat stress. The enrichment of transcription
      factor (TF) binding sites for heat shock factors, bZIPs and DREBs coupled with up
      regulation of TFs of different families suggests that the heat stress response in
      rice involves integration of various regulatory networks. The interpretation of
      microarray data in the context of coexpression network analysis identified
      several functionally correlated genes consisting of previously documented heat
      upregulated genes as well as new genes that can be implicated in heat stress.
      Based on the findings on parallel analysis of growth of seedlings, associated
      changes in transcripts of selected Hsps, genome-wide microarray profiling and the
      coexpression network analysis, this study is a step forward in understanding heat
      response of rice, the world's most important food crop.

PMID- 23975149
TI  - Evaluation of plaque detection and optimum time of enhancement in acute attack
      multiple sclerosis after contrast injection.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is important in the early diagnosis
      of novel or relapsing multiple sclerosis (MS). In addition, the optimal MRI
      protocol plays an important role in detecting MS plaques. PURPOSE: To find the
      best time to detect MS plaques on MRI after Gadobutrol injection. MATERIAL AND
      METHODS: Sixty-two relapsing-remitting type MS patients, (56 women, 6 men) with
      the mean age of 31 +/- 7 years were enrolled into this study. The patients
      underwent T1-weighted MRI scan without contrast agents. Subsequently, Gadobutrol
      was injected (0.1 mmol/kg) and MRI scanning was repeated after 30 s, 5, 10, 15,
      and 30 min of Gadobutrol injection. The size, signal intensity, and enhancement
      pattern were determined for each plaque by contrast-enhanced T1-weighted images.
      RESULTS: Enhancing plaques were seen in 42 out of 62 patients. The mean number of
      enhancing plaques was 4 +/- 8 plaques after 30 s of contrast injection. This
      figure increased to 7 +/- 13 plaques after 15 min and 6 +/- 10 plaques after 30
      min. The signal intensity and size of plaques increased progressively, and the
      maximum signal intensity and plaque size were seen after 30 min (P < 0.001).
      CONCLUSION: The maximum number of enhancing plaques in MS patients was detected
      15 min after contrast agent administration and the size and signal intensity of
      the lesions also increased remarkably at this time.

PMID- 23975150
TI  - Belief and sign, true and false: the unique of false belief reasoning.
AB  - For a long time, a controversy has been proposed that whether the process of
      theory of mind is a result of domain-specific or domain-general changes (Wellman
      in The handbook of childhood cognitive development. Blackwell Publication, New
      Jersey, 2011). This event-related potential study explored the neural time course
      of domain-general and domain-specific components in belief reasoning. Fourteen
      participants completed location transfer false belief (FB), true belief (TB),
      false sign (FS) and true sign (TS) tasks, in which two pictures told a story
      related to a dog that ran from a green into a red box. In the TB and FB tasks, a
      boy saw or did not see the transfer of the dog, respectively. In the FS and TS
      tasks, an arrow that pointed to the green box either altered its direction to the
      red box or did not alter following the transfer of the dog. Participants then
      inferred where the boy thought of, or the arrow indicated the location of the
      dog. FB and TB reasoning elicited lower N2 amplitudes than FS and TS reasoning,
      which is associated with domain-general components, the detection, and
      classification. The late slow wave (LSW) for FB was more positive at frontal,
      central, and parietal sites than FS because of the domain-specific component
      involved in FB reasoning. However, the LSW was less positive for TB than for FB
      but did not differ from the TS condition, which implies that mental
      representation might not be involved in TB reasoning. 

PMID- 23975152
TI  - Relation between gravitational and arm-movement direction in the mechanism of
      perception in bimanual steering.
AB  - This paper presents the effects of the opposing directions of gravity relative to
      right- and left-arm movement in bimanual steering. We developed a simulated
      steering system that permits independent left- and right-hand steering and torque
      presentations on a single axis, and independent measurements of the steering
      force exerted by each hand. In a steering force measurement experiment, left and
      right system units were mechanically combined to function as a single steering
      unit. Measurements of the force exerted by the participants with their left and
      right hands revealed that in human bimanual steering, the arm moving with gravity
      exerts a larger steering force than the one moving against gravity. In a steering
      force discrimination experiment, the system was mechanically configured to
      provide independence in both the function of the left and right steering units
      and the presentation of different left- and right-side steering torques. Each
      participant was then asked whether the steering force was felt to be larger on
      the left or the right during bimanual steering. The results of this experiment
      showed no difference between the left and the right arm in the discrimination
      threshold, but did reveal a perceptual bias in which the forces exerted in arm
      movements with gravity were perceived as being smaller than the forces exerted
      against gravity. Furthermore, there was no significant difference between the
      measured force and the force that would be predicted from the obtained perceptual
      bias. 

PMID- 23975153
TI  - Preparation interval and cue utilization in the prevention of distraction.
AB  - Maintaining a selective attention set allows us to efficiently perform sensory
      tasks despite the multitude of concurrent sensory stimuli. Unpredictably
      occurring, rare events nonetheless capture our attention, that is, we get
      distracted. The present study investigated the efficiency of control over
      distraction as a function of preparation time available before a forthcoming
      distracter. A random sequence of short and long tones (100 or 200 ms with 50-50 %
      probability) was presented. Independently from tone duration, occasionally (13.3
      % of the time), the pitch of a tone was changed. Such rare pitch variants
      (distracters) usually lead to delayed and less precise discrimination responses,
      and trigger a characteristic series of event-related potentials (ERPs) reflecting
      the stages of distraction-related processing: starting with negative ERPs
      signaling the sensory registration of the distracter; a P3a-usually interpreted
      as a reflection of involuntary attention change and finally the so-called
      reorienting negativity signaling the restoration of the task-optimal attention
      set. In separate conditions, 663 or 346 ms before each tone (long or short cue
      tone interval), a visual cue was presented, which signaled whether the
      forthcoming tone was a distracter (rare pitch variant), with 80 % validity. As
      reflected by reduced reaction time delays and P3a amplitudes, valid cues led to
      the prevention of distraction, but only in the long cue-tone interval condition.
      The analyses of the cue-related P3b and contingent negative variation showed that
      participants made more effort to utilize cue information to prevent distraction
      in the long cue-tone than in the short cue-tone interval condition.

PMID- 23975151
TI  - Serotonergic modulation of suicidal behaviour: integrating preclinical data with
      clinical practice and psychotherapy.
AB  - Many studies have provided important information regarding the anatomy,
      development and functional organization of the 5-HT system and the alterations in
      this system that are present within the brain of the suicidal patient. There is
      also a growing interest in genetic factors associated with suicide, since these
      may lead to the emergence of personality traits that prove to be long-term
      predictors of suicidal behaviour. This review will focus on presenting the
      scientific literature on the role of the serotonergic system in suicidal
      behaviour as well as dysfunctional attitudes and personality traits associated
      with the suicidal patient. The association of the serotonin transporter gene, the
      5-HT2 receptors and its metabolite 5-hydroxyindoleacetic acid with suicidal
      behaviour and animal models that may capture the complexity of suicidal behaviour
      will be discussed. Finally, the relationship between neurobiological models and
      psychotherapeutic interventions for suicide prevention will be considered with a
      focus on Schema Therapy (an approach that has shown particular promise in the
      treatment of suicidal individuals with personality disorders), aiming to invite
      the reader to integrate some aspects of the neurobiology of human suicidal
      behaviour into a model of suicide that can be used in a clinical encounter. 

PMID- 23975154
TI  - Combination of percutaneous radiofrequency ablation and systemic chemotherapy are
      effective treatment modalities for metachronous liver metastases from gastric
      cancer.
AB  - This study evaluated the efficacy of percutaneous radiofrequency ablation (RFA)
      for the treatment of metachronous liver metastases of gastric cancer. We enrolled
      a total of 44 patients who underwent percutaneous RFA for the treatment of
      metachronous liver metastases after resection of a primary gastric adenocarcinoma
      from January 2002 to November 2011. The primary endpoint of this study was
      overall survival (OS) and recurrence-free survival (RFS) after RFA. Systemic
      chemotherapy was combined with RFA in 40 patients; the OS and RFS of the patients
      with liver-only metastasis who underwent RFA and chemotherapy were 20.9 months
      (95% CI 18.4-23.4) and 9.8 months (95% CI 9.2-10.5), respectively. On
      multivariate analysis, the factors independently, negatively associated with OS
      were extrahepatic metastatic lesions (HR 12.6, 95% CI 3.7-42.9; p=0.001), no
      chemotherapy (HR 43.3, 95% CI 7.4-251.3; p=0.001), and tumor number>=2 (HR 2.6,
      95% CI 1.2-5.9; p=0.015). The factors independently, negatively associated with
      RFS were extrahepatic metastatic lesions (HR 3.6, 95% CI 1.6-7.8; p=0.003) and
      bilobar intrahepatic distribution (HR 3.9, 95% CI 1.5-9.9; p=0.001). The efficacy
      of percutaneous RFA for metachronous liver metastases of gastric cancer is
      limited to patients with a single, unilobar metastasis without extrahepatic
      metastatic lesions. Combined systemic chemotherapy is very important for the
      prolongation of OS.

PMID- 23975155
TI  - Endothelial-like properties of claudin-low breast cancer cells promote tumor
      vascular permeability and metastasis.
AB  - The vasculature serves as the main conduit for breast tumor metastases and is a
      target of therapeutics in many tumor types. In this study, we aimed to determine
      if tumor-associated vascular properties could help to explain the differences
      observed in metastagenicity across the intrinsic subtypes of human breast tumors.
      Analysis of gene expression signatures from more than 3,000 human breast tumors
      found that genomic programs that measured vascular quantity, vascular
      proliferation, and a VEGF/Hypoxia-signature were the most highly expressed in
      claudin-low and basal-like tumors. The majority of the vascular gene signatures
      added metastasis-predictive information to immunohistochemistry-defined
      microvessel density scores and genomically defined-intrinsic subtype
      classification. Interestingly, pure claudin-low cell lines, and subsets of
      claudin-low-like cells within established basal-like cancer cell lines, exhibited
      endothelial/tube-like morphology when cultured on Matrigel. In vivo xenografts
      found that claudin-low tumors, but not luminal tumors, extensively perfused
      injected contrast agent through paracellular spaces and non-vascular tumor-lined
      channels. Taken together, the endothelial-like characteristics of the cancer
      cells, combined with both the amount and the physiologic state of the vasculature
      contribute to breast cancer metastatic progression. We hypothesize that the
      genetic signatures we have identified highlight patients that should respond most
      favorably to anti-vascular agents. 

PMID- 23975156
TI  - Melanoma brain metastases: the impact of nodal disease.
AB  - Brain metastases (BMs) are a major source of mortality and morbidity in patients
      with melanoma. This study assesses prognostic nodal factors in patients with
      nodal metastatic melanoma with respect to the development of BMs. The aim was to
      identify a high risk subset that may benefit from brain directed management.
      Prospective surgical and clinical trial databases identified patients who had had
      nodal dissections and were seen through the Princess Alexandra Hospital Melanoma
      clinic between August 1995 and June 2010. Patient data was collected and event
      data was updated from medical imaging and clinical records. The primary endpoint
      was the rate of development of BMs. 474 patients were identified as having nodal
      dissections. Two hundred and eighty-seven patients (61%) were male with a median
      age of 52 (39-66). The most common nodal dissection site was axilla 190 (40%),
      followed by groin 154 (32.5%) and neck 130 (27.5%). Adjuvant radiotherapy to the
      nodal basin was delivered to 134 patients (28%). BMs occurred in 61 patients
      (12.9%) with a median time of 13.87 months from dissection. No lymph node
      characteristics were significantly associated with the development of BMs
      including: nodal region (p=0.72), nodal size (p=0.08), number of involved nodes
      (p=0.36), presence of extra-capsular spread (p=0.47) and AJCC N stage. There was
      no significant association between primary ulceration (p=0.37) or location and
      development of BMs. It appears that for patients with resected stage III melanoma
      there is no histopathological lymph node feature associated with the development
      of BMs. This highlights the importance of identifying molecular markers in nodal
      melanoma which may predict for BMs to further direct site-specific therapy.

PMID- 23975158
TI  - Culture proven newborn sepsis with a special emphasis on late onset sepsis caused
      by Enterobacteriaceae in a level III neonatal care unit in Astana, Kazakhstan.
AB  - BACKGROUND: Newborn sepsis is one of the major public health concerns worldwide.
      Also in our neonatal care unit, it is one of the major problems and especially
      infections with Enterobacteriaceae were noted to pose an increasing problem in
      the last years. METHODS: Data collection was done retrospectively for 2011. Early
      onset sepsis was defined as having a positive blood culture within 72 h and late
      onset sepsis after 72 h of delivery. RESULTS: Out of 599 patients being admitted,
      58 newborns were assessed having a neonatal sepsis. Of these 58 newborns with
      sepsis, 11 were diagnosed within 72 h post delivery (early onset) and 47 were
      diagnosed after 72 h post delivery (late onset). The percentage of
      Enterobacteriaceae causing late onset sepsis was 57.5 %. Among these, Klebsiella
      pneumoniae could be isolated in 29.8 %, Enterobacter cloacae in 12.8 %,
      Enterobacter aerogenes in 8.5 %, and Escherichia coli in 6.4 % of late onset
      sepsis. Majority of the strains showed a resistance to antibiotics used in
      empiric treatment. Antibiotic prophylaxis/treatment from birth until the onset of
      late onset sepsis could be analyzed in 20 out of 27 newborns with late onset
      sepsis caused by Enterobacteriaceae. A regimen of empirical antibiotic treatment
      containing aminopenicillin and/or gentamicin was administered in 16 newborns and
      that of cephalosporin in 14 out of 20 newborns for at least 5 days before onset
      of sepsis. CONCLUSIONS: The association of empiric long-term antibiotic treatment
      and the high number of late onset sepsis with often multiresistant
      Enterobacteriaceae might be causal and urges for a change in general antibiotic
      prophylaxis/treatment in newborns admitted to the neonatal care unit of our
      hospital.

PMID- 23975157
TI  - Predictive functional profiling of microbial communities using 16S rRNA marker
      gene sequences.
AB  - Profiling phylogenetic marker genes, such as the 16S rRNA gene, is a key tool for
      studies of microbial communities but does not provide direct evidence of a
      community's functional capabilities. Here we describe PICRUSt (phylogenetic
      investigation of communities by reconstruction of unobserved states), a
      computational approach to predict the functional composition of a metagenome
      using marker gene data and a database of reference genomes. PICRUSt uses an
      extended ancestral-state reconstruction algorithm to predict which gene families
      are present and then combines gene families to estimate the composite metagenome.
      Using 16S information, PICRUSt recaptures key findings from the Human Microbiome
      Project and accurately predicts the abundance of gene families in host-associated
      and environmental communities, with quantifiable uncertainty. Our results
      demonstrate that phylogeny and function are sufficiently linked that this
      'predictive metagenomic' approach should provide useful insights into the
      thousands of uncultivated microbial communities for which only marker gene
      surveys are currently available. 

PMID- 23975159
TI  - Gene expression profiles for the prediction of progression-free survival in
      diffuse large B cell lymphoma: results of a DASL assay.
AB  - We performed the whole genome cDNA-mediated annealing, selection and ligation
      assay with 164 formalin-fixed paraffin-embedded (FFPE) tumor samples to develop
      robust prognostic gene expression profiles in patients with diffuse large B cell
      lymphoma. The prognostic gene expression profiles were developed and validated by
      a gradient lasso and leave-one-out cross-validation process. We identified a set
      of genes whose expression provided prognostic indicators from whole data set
      (PRKCDBP, CASP10, FAM3C, KCNK12, MAN1A2, PRND, RAB1A, TMEM39B, SLC6A6, MMP12,
      FEM1B, C3orh37, RBP1, HK1, LOC400464, KIAA0746, and SLC25A23). This gene
      expression profile-based risk model could classify patients into two cross
      validated risk groups with a significant difference in 5-year progression-free
      survival rates (71.1 vs. 45.5 %) and with a hazard ratio for recurrence of 2.45
      (95 % CI, 1.44-4.16, P = 0.001). This model provided prognostic information
      independent of the International Prognostic Index (IPI), and discriminated high
      risk group from patients belong to high/high-intermediate risk of IPI and
      activated B cell-like type. Thus, gene expression profiling from FFPE could
      provide additional prognostic information for diffuse large B cell lymphoma and
      our data underscore the need for development of risk-adapted treatment strategies
      based on gene expression profiles.

PMID- 23975160
TI  - Conformational and NMR study of some furan derivatives by DFT methods.
AB  - 4'-substituted neutral/protonated furfurylidenanilines and trans-styrylfurans are
      able to exist in two different conformations related to the rotation around the
      furan ring-bridge double bond. In this work, the equilibrium geometry and the
      corresponding rotational barrier of the benzene ring for each furan derivative
      conformation were calculated by DFT methods. The trend and shape of the
      rotational barrier are rationalized within natural bond orbitals as well as atoms
      in-molecules approach. For the corresponding equilibrium geometries, (1)H and
      (13)C substituent induced shifts (SIS) were calculated and compared with
      experimental values. Calculated shielding constants are shown to be sensitive to
      the substituent effect through a linear fit with substituent's Hammett constants.
      An alternative approach was followed for assessing the effect of substituents
      over SIS through comparing the differences in isotropic shielding constants with
      NBO charges as well as with (1)H and (13)C experimental chemical shifts.

PMID- 23975161
TI  - Response facilitation in the four great apes: is there a role for empathy?
AB  - Contagious yawning is a form of response facilitation found in humans and other
      primates in which observing a model yawning enhances the chance that the observer
      will also yawn. Because contagious yawning seems to be more easily triggered when
      models are conspecifics or have a strong social bond with the observer, it has
      been proposed that contagious yawning is linked to empathy. A possible way to
      test this hypothesis is to analyze whether individuals' responses differ when
      they observe models yawning or performing different involuntary (i.e., nose
      wiping, scratching) and voluntary (i.e., hand closing, wrist shaking) actions
      that are not linked to empathy. In this study, we tested the four great ape
      species with two different setups by exposing them to a human experimenter
      repeatedly performing these actions online, and video-recorded conspecifics
      repeatedly performing these actions on a screen. We examined which behaviors were
      subject to response facilitation, whether response facilitation was triggered by
      both human models and video-recorded conspecifics, and whether all species showed
      evidence of response facilitation. Our results showed that chimpanzees yawned
      significantly more when and shortly after watching videos of conspecifics (but
      not humans) yawning than in control conditions, and they did not do so as a
      response to increased levels of anxiety. For all other behaviors, no species
      produced more target actions when being exposed to either model than under
      control conditions. Moreover, the individuals that were more "reactive" when
      watching yawning videos were not more reactive when exposed to other actions.
      Since, at least in chimpanzees, (1) subjects only showed response facilitation
      when they were exposed to yawning and (2) only if models were conspecifics, it
      appears that contagious yawning is triggered by unique mechanisms and might be
      linked to empathy. 

PMID- 23975162
TI  - Range extension of the vulnerable dwarf marmoset, Callibella humilis (Roosmalen
      et al. 1998), and first analysis of its long call structure.
AB  - We present two new records for the vulnerable dwarf marmoset, Callibella humilis.
      The first record, based on observed and photographed individuals, is from a
      campinarana area on the left (west) bank of the Rio Madeirinha, a left (west)
      bank tributary of the Rio Roosevelt in the state of Amazonas, municipality of
      Novo Aripuana and extends the distribution of the species ~270 km southwards, to
      the left (west) bank of the rio Roosevelt. The second record is based on an
      individual collected from the mouth of the Rio Roosevelt, at less than 10 km from
      the type locality of Mico marcai. This indicates that the species occurs
      sympatrically with M. marcai and probably Mico melanurus. We also present the
      first sonogram analysis of its long call structure, which shows some
      similarities, in the note duration and frequency, with Cebuella pygmaea and Mico
      argentatus. 

PMID- 23975163
TI  - Effect of qubi zhentong recipe on synovial gene expression in collagen-induced
      arthritis in rats.
AB  - OBJECTIVE: To investigate the effect of the Chinese medical formula Qubi Zhentong
      Recipe(, QZR) on the synovial gene expression profile in collagen-induced
      arthritis (CIA) rats. METHODS: Ten rats were randomly chosen from 60 rats as the
      control group, and the other 50 rats were used for the CIA models. The CIA model
      group was constructed by bovine injection of type II collagen through the rats'
      neck and tail. Twenty rats were randomly chosen from 34 successful CIA models and
      randomly assigned into two groups: the model group (n =10) and the QZR group
      (n=10). The QZR group was fed intragastrically with QZR 22.9 g/(kg.d) (10 times
      the clinical adult dose), and the CIA model group was given the same dose of
      normal saline. Both model and QZR groups were administered treatment once a day.
      Total RNA was collected from the knee joint synovium after 30 days. The change in
      gene expression profile was analyzed by a whole gene chip. RESULTS: A total of 76
      genes showed a difference in expression between CIA model group and the control
      group; 35 genes were down-regulated and 41 were up-regulated. A total of 67 genes
      showed a difference in expression between the model group and the QZR group; 48
      genes were down-regulated and 19 were upregulated. CONCLUSIONS: QZR may affect
      CIA by stimulating multiple genes and targets, which are related to oncogenes,
      apoptosis, metabolism, the immune system, ion channels, and transport proteins.

PMID- 23975164
TI  - Correlation between different Chinese medicine syndromes and changes in
      microcirculation in septic shock patients.
AB  - OBJECTIVE: To investigate the correlation between different Chinese medicine (CM)
      syndromes and variations in microcirculation in septic shock patients. METHODS:
      seventy Septic shock patients were divided into four groups: heat damaging qi-yin
      group (HDQY, 23 cases); yin exhaustion and yang collapse group (YEYC, 26 cases);
      excessive heat in Fu organ group (EHFO, 10 cases); and heat damaging nutrient
      blood group (HDNB, 11 cases). Sublingual microcirculation parameters were
      observed by sidestream dark-field (SDF) imaging and scored by Acute Physiology
      and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure
      Assessment (SOFA), and parameters of microcirculation perfusion variations and
      prognoses were analyzed. RESULTS: Compared with those with qi-yin heat damage,
      perfused vessel density (PVD) in other groups decreased dramatically (P<0.05),
      and APACHE II scores increased significantly (P<0.05). In addition, the recovery
      time was prolonged substantially (P<0.05), and the mixed venous oxygen saturation
      (SVO2) decreased (P<0.05). Blood lactic acid increased significantly (P<0.05),
      and the mixed SVO decreased (P<0.05), in the YEYC group. Compared with the
      thermal injury camp blood group, sublingual microcirculation parameter variations
      showed no obvious difference in the YEYC and EHFO groups (P>0.05). There were
      significant positive correlations between CM syndromes and APACHE II scoring in
      different groups (r=0.512, P<0.05). There were negative correlations between PVD
      and APACHE II scoring (r=-0.378, P=0.043), the proportion of perfused vessels
      (PPV) and APACHE II scoring (r=-0.472, P=0.008), as well as between the
      microvascular flow index (MFI) and APACHE II scoring (r=-0.424, P=0.023) in
      different patients. CONCLUSION: Sublingual microcirculation may serve as a
      clinical diagnostic parameter of the patient condition, as well as being a
      prognostic indicator.

PMID- 23975165
TI  - Differential proinflammatory and oxidative stress response and vulnerability to
      metabolic syndrome in habitual high-fat young male consumers putatively
      predisposed by their genetic background.
AB  - The current nutritional habits and lifestyles of modern societies favor energy
      overloads and a diminished physical activity, which may produce serious clinical
      disturbances and excessive weight gain. In order to investigate the mechanisms by
      which the environmental factors interact with molecular mechanisms in obesity, a
      pathway analysis was performed to identify genes differentially expressed in
      subcutaneous abdominal adipose tissue (SCAAT) from obese compared to lean male
      (21-35 year-old) subjects living in similar obesogenic conditions: habitual high
      fat dietary intake and moderate physical activity. Genes involved in inflammation
      (ALCAM, CTSB, C1S, YKL-40, MIF, SAA2), extracellular matrix remodeling (MMP9,
      PALLD), angiogenesis (EGFL6, leptin) and oxidative stress (AKR1C3, UCHL1, HSPB7
      and NQO1) were upregulated; whereas apoptosis, signal transcription (CITED 2 and
      NR3C1), cell control and cell cycle-related genes were downregulated.
      Interestingly, the expression of some of these genes (C1S, SAA2, ALCAM, CTSB, YKL
      40 and tenomodulin) was found to be associated with some relevant metabolic
      syndrome features. The obese group showed a general upregulation in the
      expression of inflammatory, oxidative stress, extracellular remodeling and
      angiogenic genes compared to lean subjects, suggesting that a given genetic
      background in an obesogenic environment could underlie the resistance to gaining
      weight and obesity-associated manifestations. 

PMID- 23975166
TI  - Assessing the effect of loop mutations in the folding space of beta2
      microglobulin with molecular dynamics simulations.
AB  - We use molecular dynamics simulations of a full atomistic Go model to explore the
      impact of selected DE-loop mutations (D59P and W60C) on the folding space of
      protein human beta2-microglobulin (Hbeta2m), the causing agent of dialysis
      related amyloidosis, a conformational disorder characterized by the deposition of
      insoluble amyloid fibrils in the osteoarticular system. Our simulations replicate
      the effect of mutations on the thermal stability that is observed in experiments
      in vitro. Furthermore, they predict the population of a partially folded state,
      with 60% of native internal free energy, which is akin to a molten globule. In
      the intermediate state, the solvent accessible surface area increases up to 40
      times relative to the native state in 38% of the hydrophobic core residues,
      indicating that the identified species has aggregation potential. The
      intermediate state preserves the disulfide bond established between residue Cys25
      and residue Cys80, which helps maintain the integrity of the core region, and is
      characterized by having two unstructured termini. The movements of the termini
      dominate the essential modes of the intermediate state, and exhibit the largest
      displacements in the D59P mutant, which is the most aggregation prone variant.
      PROPKA predictions of pKa suggest that the population of the intermediate state
      may be enhanced at acidic pH explaining the larger amyloidogenic potential
      observed in vitro at low pH for the WT protein and mutant forms.

PMID- 23975168
TI  - Low amount of salinomycin greatly increases Akt activation, but reduces activated
      p70S6K levels.
AB  - The present study identified a novel salinomycin (Sal)-sensitization mechanism in
      cancer cells. We analyzed the signal proteins Akt, Jnk, p38, Jak, and Erk1/2 in
      cancer cell lines that had arrested growth following low amounts of Sal
      treatment. We also tested the signal molecules PI3K, PDK1, GSK3beta, p70S6K,
      mTOR, and PTEN to analyze the PI3K/Akt/mTOR pathway. The results showed that Sal
      sensitization positively correlates with large reductions in p70S6K activation.
      Interestingly, Akt was the only signal protein to be significantly activated by
      Sal treatment. The Akt activation appeared to require the PI3K pathway as its
      activation was abolished by the PI3K inhibitors LY294002 and wortmannin. The Akt
      activation by Sal was conserved in the other cell lines analyzed, which
      originated from other organs. Both Akt activation and C-PARP production were
      proportionally increased with increased doses of Sal. In addition, the increased
      levels of pAkt were not reduced over the time course of the experiment. Co
      treatment with Akt inhibitors sensitized the Sal-treated cancer cells. The
      results thereby suggest that Akt activation is increased in cells that survive
      Sal treatment and resist the cytotoxic effect of Sal. Taken together; these
      results indicate that Akt activation may promote the resistance of cancer cells
      to Sal. 

PMID- 23975167
TI  - Potential targets for colorectal cancer prevention.
AB  - The step-wise development of colorectal neoplasia from adenoma to carcinoma
      suggests that specific interventions could delay or prevent the development of
      invasive cancer. Several key factors involved in colorectal cancer pathogenesis
      have already been identified including cyclooxygenase 2 (COX-2), nuclear factor
      kappa B (NF-kappaB), survivin and insulin-like growth factor-I (IGF-I). Clinical
      trials of COX-2 inhibitors have provided the "proof of principle" that inhibition
      of this enzyme can prevent the formation of colonic adenomas and potentially
      carcinomas, however concerns regarding the potential toxicity of these drugs have
      limited their use as a chemopreventative strategy. Curcumin, resveratrol and
      quercetin are chemopreventive agents that are able to suppress multiple signaling
      pathways involved in carcinogenesis and hence are attractive candidates for
      further research. 

PMID- 23975169
TI  - Oxidative stress and microRNAs in vascular diseases.
AB  - Oxidative stress has been demonstrated to play a causal role in different
      vascular diseases, such as hypertension, diabetic vasculopathy,
      hypercholesterolemia and atherosclerosis. Indeed, increased reactive oxygen
      species (ROS) production is known to impair endothelial and vascular smooth
      muscle cell functions, contributing to the development of cardiovascular
      diseases. MicroRNAs (miRNAs) are non-coding RNA molecules that modulate the
      stability and/or the translational efficiency of target messenger RNAs. They have
      been shown to be modulated in most biological processes, including in cellular
      responses to redox imbalance. In particular, miR-200 family members play a
      crucial role in oxidative-stress dependent endothelial dysfunction, as well as in
      cardiovascular complications of diabetes and obesity. In addition, different
      miRNAs, such as miR-210, have been demonstrated to play a key role in
      mitochondrial metabolism, therefore modulating ROS production and sensitivity. In
      this review, we will discuss miRNAs modulated by ROS or involved in ROS
      production, and implicated in vascular diseases in which redox imbalance has a
      pathogenetic role. 

PMID- 23975171
TI  - GISTogram: a graphic presentation of the growing GIST complexity.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract. They have represented a paradigm of molecular
      targeted therapies for solid tumors since the discovery of KIT mutations and KIT
      expression in GIST in 1998, which opened the way to the use of imatinib, a
      tyrosine kinase inhibitor able to inhibit the growth of cells expressing KIT
      mutant isoforms. Since then, accumulating evidence revealed the rather
      heterogeneous nature of GIST, implying possible different diagnostic and
      therapeutic approaches for each specific case, leading to the development of
      drugs alternative to imatinib. In this brief commentary, we graphically represent
      the historical growing of genotype and phenotype evidence on GIST since 1998 in
      its increasing complexity by building up a graph, which we have called
      "GISTogram", that visually conveys most of GIST-characterizing features and the
      probability for each of them, either alone or in combination, to be observed in a
      single GIST case. 

PMID- 23975172
TI  - Audit of the informed consent process as a part of a clinical research quality
      assurance program.
AB  - Audits of the informed consent process are a key element of a clinical research
      quality assurance program. A systematic approach to such audits has not been
      described in the literature. In this paper we describe two components of the
      audit. The first is the audit of the informed consent document to verify
      adherence with federal regulations. The second component is comprised of the
      audit of the informed consent conference, with emphasis on a real time review of
      the appropriate communication of the key elements of the informed consent.
      Quality measures may include preparation of an informed consent history log,
      notes to accompany the informed consent, the use of an informed consent feedback
      tool, and the use of institutional surveys to assess comprehension of the
      informed consent process. 

PMID- 23975173
TI  - Electronic monitoring of offenders: an ethical review.
AB  - This paper considers electronic monitoring (EM) a promising alternative to
      imprisonment as a criminal sanction for a series of criminal offenses. However,
      little has been said about EM from an ethical perspective. To evaluate EM from an
      ethical perspective, six initial ethical challenges are addressed and discussed.
      It is argued that since EM is developing as a technology and a punitive means, it
      is urgent to discuss its ethical implications and incorporate moral values into
      its design and development. 

PMID- 23975170
TI  - Dynamic nature of noncoding RNA regulation of adaptive immune response.
AB  - Immune response plays a fundamental role in protecting the organism from
      infections; however, dysregulation often occurs and can be detrimental for the
      organism, leading to a variety of immune-mediated diseases. Recently our
      understanding of the molecular and cellular networks regulating the immune
      response, and, in particular, adaptive immunity, has improved dramatically. For
      many years, much of the focus has been on the study of protein regulators;
      nevertheless, recent evidence points to a fundamental role for specific classes
      of noncoding RNAs (ncRNAs) in regulating development, activation and homeostasis
      of the immune system. Although microRNAs (miRNAs) are the most comprehensive and
      well-studied, a number of reports suggest the exciting possibility that long
      ncRNAs (lncRNAs) could mediate host response and immune function. Finally,
      evidence is also accumulating that suggests a role for miRNAs and other small
      ncRNAs in autocrine, paracrine and exocrine signaling events, thus highlighting
      an elaborate network of regulatory interactions mediated by different classes of
      ncRNAs during immune response. This review will explore the multifaceted roles of
      ncRNAs in the adaptive immune response. In particular, we will focus on the well
      established role of miRNAs and on the emerging role of lncRNAs and circulating
      ncRNAs, which all make indispensable contributions to the understanding of the
      multilayered modulation of the adaptive immune response. 

PMID- 23975174
TI  - When technologies makes good people do bad things: another argument against the
      value-neutrality of technologies.
AB  - Although many scientists and engineers insist that technologies are value
      neutral, philosophers of technology have long argued that they are wrong. In this
      paper, I introduce a new argument against the claim that technologies are value
      neutral. This argument complements and extends, rather than replaces, existing
      arguments against value-neutrality. I formulate the Value-Neutrality Thesis,
      roughly, as the claim that a technological innovation can have bad effects, on
      balance, only if its users have "vicious" or condemnable preferences. After
      sketching a microeconomic model for explaining or predicting a technology's
      impact on individuals' behavior, I argue that a particular technological
      innovation can create or exacerbate collective action problems, even in the
      absence of vicious preferences. Technologies do this by increasing the net
      utility of refusing to cooperate. I also argue that a particular technological
      innovation can induce short-sighted behavior because of humans' tendency to
      discount future benefits too steeply. I suggest some possible extensions of my
      microeconomic model of technological impacts. These extensions would enable
      philosophers of technology to consider agents with mixed motives-i.e., agents who
      harbor some vicious preferences but also some aversion to acting on them-and to
      apply the model to questions about the professional responsibilities of
      engineers, scientists, and other inventors. 

PMID- 23975175
TI  - Genetic correction of HAX1 in induced pluripotent stem cells from a patient with
      severe congenital neutropenia improves defective granulopoiesis.
AB  - HAX1 was identified as the gene responsible for the autosomal recessive type of
      severe congenital neutropenia. However, the connection between mutations in the
      HAX1 gene and defective granulopoiesis in this disease has remained unclear,
      mainly due to the lack of a useful experimental model for this disease. In this
      study, we generated induced pluripotent stem cell lines from a patient presenting
      for severe congenital neutropenia with HAX1 gene deficiency, and analyzed their
      in vitro neutrophil differentiation potential by using a novel serum- and feeder
      free directed differentiation culture system. Cytostaining and flow cytometric
      analyses of myeloid cells differentiated from patient-derived induced pluripotent
      stem cells showed arrest at the myeloid progenitor stage and apoptotic
      predisposition, both of which replicated abnormal granulopoiesis. Moreover,
      lentiviral transduction of the HAX1 cDNA into patient-derived induced pluripotent
      stem cells reversed disease-related abnormal granulopoiesis. This in vitro
      neutrophil differentiation system, which uses patient-derived induced pluripotent
      stem cells for disease investigation, may serve as a novel experimental model and
      a platform for high-throughput screening of drugs for various congenital
      neutrophil disorders in the future. 

PMID- 23975176
TI  - Stem cell mobilization in HIV seropositive patients with lymphoma.
AB  - High-dose chemotherapy with autologous peripheral blood stem cell rescue has been
      reported as feasible and effective in HIV-associated lymphoma. Although a
      sufficient number of stem cells seems achievable in most patients, there are
      cases of stem cell harvest failure. The aim of this study was to describe the
      mobilization policies used in HIV-associated lymphoma, evaluate the failure rate
      and identify factors influencing mobilization results. We analyzed 155 patients
      who underwent attempted stem cell mobilization at 10 European centers from 2000
      2012. One hundred and twenty patients had non-Hodgkin lymphoma and 35 Hodgkin
      lymphoma; 31% had complete remission, 57% chemosensitive disease, 10% refractory
      disease, 2% untested relapse. Patients were mobilized with chemotherapy + G-CSF
      (86%) or G-CSF alone (14%); 73% of patients collected >2 and 48% >5 * 10(6)
      CD34(+) cells/kg. Low CD4+ count and refractory disease were associated with
      mobilization failure. Low CD4(+) count, low platelet count and mobilization with
      G-CSF correlated with lower probability to achieve >5 * 10(6) CD34(+) cells/kg,
      whereas cyclophosphamide >= 3 g/m(2) + G-CSF predicted higher collections.
      Circulating CD34(+) cells and CD34/WBC ratio were strongly associated with
      collection result. HIV infection alone should not preclude an attempt to obtain
      stem cells in candidates for autologous transplant as the results are comparable
      to the HIV-negative population.

PMID- 23975177
TI  - Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell
      precursor acute lymphoblastic leukemia gene signature and typically have non
      rearranged T-cell receptors.
AB  - Three distinct immature T-cell acute lymphoblastic leukemia entities have been
      described including cases that express an early T-cell precursor immunophenotype
      or expression profile, immature MEF2C-dysregulated T-cell acute lymphoblastic
      leukemia cluster cases based on gene expression analysis (immature cluster) and
      cases that retain non-rearranged TRG@ loci. Early T-cell precursor acute
      lymphoblastic leukemia cases exclusively overlap with immature cluster samples
      based on the expression of early T-cell precursor acute lymphoblastic leukemia
      signature genes, indicating that both are featuring a single disease entity.
      Patients lacking TRG@ rearrangements represent only 40% of immature cluster
      cases, but no further evidence was found to suggest that cases with absence of bi
      allelic TRG@ deletions reflect a distinct and even more immature disease entity.
      Immature cluster/early T-cell precursor acute lymphoblastic leukemia cases are
      strongly enriched for genes expressed in hematopoietic stem cells as well as
      genes expressed in normal early thymocyte progenitor or double negative-2A T-cell
      subsets. Identification of early T-cell precursor acute lymphoblastic leukemia
      cases solely by defined immunophenotypic criteria strongly underestimates the
      number of cases that have a corresponding gene signature. However, early T-cell
      precursor acute lymphoblastic leukemia samples correlate best with a CD1
      negative, CD4 and CD8 double negative immunophenotype with expression of CD34
      and/or myeloid markers CD13 or CD33. Unlike various other studies, immature
      cluster/early T-cell precursor acute lymphoblastic leukemia patients treated on
      the COALL-97 protocol did not have an overall inferior outcome, and demonstrated
      equal sensitivity levels to most conventional therapeutic drugs compared to other
      pediatric T-cell acute lymphoblastic leukemia patients. 

PMID- 23975178
TI  - Clonal analysis of multipotent stromal cells derived from CD271+ bone marrow
      mononuclear cells: functional heterogeneity and different mechanisms of
      allosuppression.
AB  - Previous reports demonstrated a relationship between proliferation potential and
      trilineage differentiation in mesenchymal stromal cell-derived clones generated
      using plastic adherence (PA-MSCs). However, there are no reports presenting a
      clonal analysis of the proliferative potential, differentiation potential and
      allosuppressive effects of human mesenchymal stromal cell subsets. In this study,
      we performed a clonal analysis of mesenchymal stromal cells generated from human
      CD271(+) bone marrow mononuclear cells (CD271-MSCs). After transfection with the
      gene encoding green fluorescent protein, the cells were single-cell sorted and
      cultured for 2-4 weeks. A population doubling analysis demonstrated that 25% of
      CD271-MSC clones are fast-proliferating clones compared to only 10% of PA-MSC
      clones. Evaluation of the allosuppressive potential demonstrated that 81.8% of
      CD271-MSC clones were highly allosuppressive compared to only 58% of PA-MSC
      clones. However, no consistent correlation was observed between allosuppression
      and proliferative potential. Prostaglandin E2 levels were positively correlated
      with the allosuppressive activity of individual clones, suggesting that this
      molecule may be a useful predictive biomarker for the allosuppressive potential
      of mesenchymal stromal cells. In contrast, inhibitory studies of indoleamine 2,3
      dioxygenase indicated that none of the clones used this enzyme to mediate their
      allosuppressive effect. Differentiation studies revealed the presence of
      tripotent, bipotent and unipotent CD271-MSC and PA-MSC clones which suppressed
      the allogeneic reaction to differing extents in vitro. In conclusion, our
      findings demonstrate differences between CD271-MSCs and PA-MSCs and indicate that
      neither proliferation potential nor differentiation potential represents a
      consistent predictive parameter for the immunomodulatory effects of either type
      of mesenchymal stromal cells. 

PMID- 23975179
TI  - Prognostic impact of day 15 blast clearance in risk-adapted remission induction
      chemotherapy for younger patients with acute myeloid leukemia: long-term results
      of the multicenter prospective LAM-2001 trial by the GOELAMS study group.
AB  - Early response to chemotherapy has a major prognostic impact in acute myeloid
      leukemia patients treated with a double induction strategy. Less is known about
      patients treated with standard-dose cytarabine and anthracycline. We designed a
      risk-adapted remission induction regimen in which a second course of intermediate
      dose cytarabine was delivered after standard "7+3" only if patients had 5% or
      more bone marrow blasts 15 days after chemotherapy initiation (d15-blasts). Of
      823 included patients, 795 (96.6%) were evaluable. Five hundred and forty-five
      patients (68.6%) had less than 5% d15-blasts. Predictive factors for high d15
      blasts were white blood cell count (P<0.0001) and cytogenetic risk (P<0.0001).
      Patients with fewer than 5% d15-blasts had a higher complete response rate (91.7%
      vs. 69.2%; P<0.0001) and a lower induction death rate (1.8% vs. 6.8%; P=0.001).
      Five-year event-free (48.4% vs. 25%; P<0.0001), relapse-free (52.7% vs. 36.9%;
      P=0.0016) and overall survival (55.3% vs. 36.5%; P<0.0001) were significantly
      higher in patients with d15-blasts lower than 5%. Multivariate analyses
      identified d15-blasts and cytogenetic risk as independent prognostic factors for
      the three end points. Failure to achieve early blast clearance remains a poor
      prognostic factor even after early salvage. By contrast, early responding
      patients have a favorable outcome without any additional induction course.
      (ClinicalTrials.gov identifier NCT01015196). 

PMID- 23975180
TI  - STAT3-mediated activation of microRNA cluster 17~92 promotes proliferation and
      survival of ALK-positive anaplastic large cell lymphoma.
AB  - Systemic anaplastic large cell lymphoma is a category of T-cell non-Hodgkin's
      lymphoma which can be further subdivided into two distinct entities (ALK(+) and
      ALK(-)) based on the presence or absence of ALK gene rearrangements. Among
      several pathways triggered by ALK signaling, constitutive activation of STAT3 is
      strictly required for ALK-mediated transformation and survival. Here we performed
      genome-wide microRNA profiling and identified 48 microRNA concordantly modulated
      by the inducible knock-down of ALK and STAT3. To evaluate the functional role of
      differentially expressed miRNA, we forced their expression in ALK(+) anaplastic
      large cell lymphoma cells, and monitored their influence after STAT3 depletion.
      We found that the expression of the microRNA-17~92 cluster partially rescues
      STAT3 knock-down by sustaining proliferation and survival of ALK(+) cells.
      Experiments in a xenograft mouse model indicated that forced expression of
      microRNA-17~92 interferes with STAT3 knock-down in vivo. High expression levels
      of the microRNA-17~92 cluster resulted in down-regulation of BIM and TGFbetaRII
      proteins, suggesting that their targeting might mediate resistance to STAT3 knock
      down in anaplastic large cell lymphoma cells. We speculate that the microRNA
      17~92 cluster is involved in lymphomagenesis of STAT3(+) ALCL and that its
      inhibition might represent an alternative avenue to interfere with ALK signaling
      in anaplastic large cell lymphomas. 

PMID- 23975181
TI  - Increased reactive oxygen species production and p47phox phosphorylation in
      neutrophils from myeloproliferative disorders patients with JAK2 (V617F)
      mutation.
AB  - Myeloproliferative disorders are associated with increased risk of thrombosis and
      vascular complications. The pathogenesis of these complications is not completely
      known. Reactive oxygen species produced by the neutrophil NADPH oxidase could
      have a role in this process. The aim of this study was to evaluate reactive
      oxygen species production by neutrophils of myeloproliferative disorder patients.
      Patients with or without the JAK2 V617F mutation were characterized. Reactive
      oxygen species production was assessed by chemiluminescence, and phosphorylation
      of the NADPH oxidase subunit p47phox was analyzed by Western blots. In a
      comparison of controls and myeloproliferative disorder patients without the JAK2
      V617F mutation, reactive oxygen species production by neutrophils from patients
      with the JAK2 V617F mutation was dramatically increased in non-stimulated and in
      stimulated conditions. This increase was associated with increased
      phosphorylation of the p47phox on Ser345 and of the uspstream kinase ERK1/2. In
      neutrophils from healthy donors, JAK2 can be activated by GM-CSF. GM-CSF-induced
      p47phox phosphorylation and priming of reactive oxygen species production are
      inhibited by the selective JAK2 inhibitors AG490 and lestaurtinib (CEP-701),
      supporting a role for JAK2 in the upregulation of NADPH oxidase activation. These
      findings show an increase in reactive oxygen species production and p47phox
      phosphorylation in neutrophils from myeloproliferative disorder patients with the
      JAK2 V617F mutation, and demonstrate that JAK2 is involved in GM-CSF-induced
      NADPH oxidase hyperactivation. As neutrophil hyperactivation could be implicated
      in the thrombophilic status of patients with myeloproliferative disorders,
      aberrant activation of JAK2 V617F, leading to excessive neutrophil reactive
      oxygen species production might play a role in this setting. 

PMID- 23975183
TI  - Tuning the Kondo effect in thin Au films by depositing a thin layer of Au on
      molecular spin-dopants.
AB  - We report on the tuning of the Kondo effect in thin Au films containing a
      monolayer of cobalt(II) terpyridine complexes by altering the ligand structure
      around the Co(2+) ions by depositing a thin Au capping layer on top of the
      monolayer on Au by magnetron sputtering (more energetic) and e-beam evaporation
      (softer). We show that the Kondo effect is slightly enhanced with respect to that
      of the uncapped film when the cap is deposited by evaporation, and significantly
      enhanced when magnetron sputtering is used. The Kondo temperature (TK) increases
      from 3 to 4.2/6.2 K for the evaporated/sputtered caps. X-ray absorption
      spectroscopy and surface-enhanced Raman spectroscopy investigation showed that
      the organic ligands remain intact upon Au e-beam evaporation; however, sputtering
      inflicts significant change in the Co(2+) electronic environment. The location of
      the monolayer-on the surface or embedded in the film-has a small effect. However,
      the damage of Co-N bonds induced by sputtering has a drastic effect on the
      increase of the impurity-electron interaction. This opens up the way for tuning
      of the magnetic impurity states, e.g. spin quantum number, binding energy with
      respect to the host Fermi energy, and overlap via the ligand structure around the
      ions. 

PMID- 23975182
TI  - Resveratrol accelerates erythroid maturation by activation of FoxO3 and
      ameliorates anemia in beta-thalassemic mice.
AB  - Resveratrol, a polyphenolic-stilbene, has received increased attention in the
      last decade due to its wide range of biological activities. Beta(beta)
      thalassemias are inherited red cell disorders, found worldwide, characterized by
      ineffective erythropoiesis and red cell oxidative damage with reduced survival.
      We evaluated the effects of low-dose-resveratrol (5 MUM) on in vitro human
      erythroid differentiation of CD34(+) from normal and beta-thalassemic subjects.
      We found that resveratrol induces accelerated erythroid-maturation, resulting in
      the reduction of colony-forming units of erythroid cells and increased
      intermediate and late erythroblasts. In sorted colony-forming units of erythroid
      cells resveratrol activates Forkhead-box-class-O3, decreases Akt activity and up
      regulates anti-oxidant enzymes as catalase. In an in vivo murine model for beta
      thalassemia, resveratrol (2.4 mg/kg) reduces ineffective erythropoiesis,
      increases hemoglobin levels, reduces reticulocyte count and ameliorates red cell
      survival. In both wild-type and beta-thalassemic mice, resveratrol up-regulates
      scavenging enzymes such as catalase and peroxiredoxin-2 through Forkhead-box
      class-O3 activation. These data indicate that resveratrol inhibits Akt resulting
      in FoxO3 activation with upregulation of cytoprotective systems enabling the
      pathological erythroid precursors to resist the oxidative damage and continue to
      differentiate. Our data suggest that the dual effect of resveratrol on
      erythropoiesis through activation of FoxO3 transcriptional factor combined with
      the amelioration of oxidative stress in circulating red cells may be considered
      as a potential novel therapeutic strategy in treating beta-thalassemia. 

PMID- 23975184
TI  - Inflammatory cytokine levels and breast cancer risk factors: racial differences
      of healthy Caucasian and African American women.
AB  - PURPOSE/OBJECTIVES: To examine racial differences in inflammatory cytokine levels
      (interleukin [IL]-6 and interferon-gamma [IFN-gamma]) and breast cancer (BC) risk
      factors between healthy Caucasian and African American women; to examine
      differences in relationships of inflammatory cytokine levels with BC risk factors
      between these groups of women; and to determine the independent contribution of
      race to IL-6 and IFN-gamma after controlling for relevant covariates. DESIGN:
      Cross-sectional and correlational descriptive design. SETTING: Community
      surrounding a state university health system in the southeastern United States.
      SAMPLE: 113 healthy women (65 Caucasians and 48 African Americans) aged 20 years
      or older and not pregnant. METHODS: Secondary analysis of data collected from
      self-report questionnaires and blood samples. MAIN RESEARCH VARIABLES:
      Inflammatory cytokine levels, BC risk factors (age, age at menarche, age at first
      live birth, family history of BC, breast biopsy, breastfeeding history and
      duration, body mass index, and physical activity), and race. FINDINGS:
      Significant racial differences were noted in IL-6 and IFN-gamma levels,
      reproductive or hormonal and lifestyle BC risk factors, and relationships between
      African American and Caucasian women. Controlling for all other effects, race
      appeared to be a significant predictor for IL-6 and IFN-gamma. CONCLUSIONS:
      Racial differences in inflammatory cytokines and BC risk factors may provide
      partial evidence for existing racial disparities in BC for African American and
      Caucasian women. Additional studies are needed to confirm that potential.
      IMPLICATIONS FOR NURSING: Additional biobehavioral research in racial disparities
      in BC may help to inform nurses to target race-specific modifications of
      lifestyle and behavioral factors to reduce BC health disparity between African
      American and Caucasian women. KNOWLEDGE TRANSLATION: Being an African American
      woman predicted a higher level of inflammatory cytokine production after
      controlling for selected BC risk factors. Great potential exists for inflammatory
      responses as one of the underlying biologic mechanisms for existing BC disparity
      and for culturally tailored lifestyle or behavioral modification interventions
      for reducing BC risk and racial disparity.

PMID- 23975185
TI  - A randomized controlled trial of balance training during pulmonary rehabilitation
      for individuals with COPD.
AB  - BACKGROUND: Deficits in balance are increasingly recognized among the important
      secondary impairments in COPD. The purpose of this study was to investigate the
      effect of a balance-training program on measures of balance and physical function
      in patients with COPD enrolled in pulmonary rehabilitation (PR). METHODS:
      Patients were assigned randomly to an intervention or control group. The
      intervention group underwent balance training three times a week for 6 weeks
      concurrently with PR. The control group received only the 6-week PR program.
      Clinical balance measures included the Berg Balance Scale (BBS), the Balance
      Evaluation Systems Test (BESTest), and the Activities-Specific Balance Confidence
      (ABC) scale. The physical function subscale of the 36-Item Short Form Health
      Survey (PF-10) and the 30-s chair-stand test were used to measure self-reported
      physical function and lower-extremity muscle strength, respectively. RESULTS:
      Thirty-nine patients with COPD (mean FEV1, 37.5% +/- 15.6% predicted) were
      enrolled in the study. Mean compliance with the balance-training program was
      82.5%, and no adverse events were reported. Compared with control subjects,
      scores on the BBS (P < .01), BESTest (P < .01), PF-10 (P = .01), and 30-s chair
      stand (P = .02) were significantly improved in the intervention group. No
      significant between-group differences were found in change scores on the ABC
      scale (P = .2). CONCLUSIONS: Our results support the feasibility and
      effectiveness of balance training as part of PR for improving balance
      performance, muscle strength, and self-reported physical function in patients
      with moderate to severe COPD.

PMID- 23975186
TI  - Methylation loss at H19 imprinted gene correlates with methylenetetrahydrofolate
      reductase gene promoter hypermethylation in semen samples from infertile males.
AB  - Aberrant methylation at the H19 paternal imprinted gene has been identified in
      different cohorts of infertile males. The causes of H19 methylation errors are
      poorly understood. In this study, we investigated the methylation status of the
      H19 gene in semen DNA samples from infertile males affected by MTHFR gene
      promoter hypermethylation. DNA from normal and abnormal semen samples harbouring
      MTHFR gene promoter hypermethylated, hmMTHFR-nor and hmMTHFR-abn, and without
      MTHFR methylation, MTHFR-nor and MTHFR-abn, were investigated for methylation
      status in the H19 locus using bisulfite-treated DNA PCR, followed by cloning and
      sequencing. The prevalence of H19 hypomethylated clones was 20% in hmMTHFR-nor
      and 0% in MTHFR-nor semen samples (p<0.05), and 28% in hmMTHFR-abn compared with
      16% in MTHFR-abn semen samples (p>0.05). These results underscore the association
      between H19 methylation defects and hypermethylation of the MTHFR gene promoter
      in normal semen samples and suggest that aberrant methylation at H19 may occur in
      the normal sperm of infertile males affected by MTHFR gene dysfunction. These
      findings provide new insights into the mechanisms causing abnormal methylation in
      imprinted genes and, in turn, male infertility.

PMID- 23975187
TI  - Atypical presentation of genital herpes simplex (HSV-2) in two patients with
      chronic lymphocytic leukemia.

PMID- 23975188
TI  - Hierarchical patterns of three-dimensional block-copolymer films formed by
      electrohydrodynamic jet printing and self-assembly.
AB  - Self-assembly of block-copolymers provides a route to the fabrication of small
      (size, <50 nm) and dense (pitch, <100 nm) features with an accuracy that
      approaches even the demanding specifications for nanomanufacturing set by the
      semiconductor industry. A key requirement for practical applications, however, is
      a rapid, high-resolution method for patterning block-copolymers with different
      molecular weights and compositions across a wafer surface, with complex
      geometries and diverse feature sizes. Here we demonstrate that an ultrahigh
      resolution jet printing technique that exploits electrohydrodynamic effects can
      pattern large areas with block-copolymers based on poly(styrene-block-methyl
      methacrylate) with various molecular weights and compositions. The printed
      geometries have diameters and linewidths in the sub-500 nm range, line edge
      roughness as small as ~45 nm, and thickness uniformity and repeatability that can
      approach molecular length scales (~2 nm). Upon thermal annealing on bare, or
      chemically or topographically structured substrates, such printed patterns yield
      nanodomains of block-copolymers with well-defined sizes, periodicities and
      morphologies, in overall layouts that span dimensions from the scale of
      nanometres (with sizes continuously tunable between 13 nm and 20 nm) to
      centimetres. As well as its engineering relevance, this methodology enables
      systematic studies of unusual behaviours of block-copolymers in geometrically
      confined films. 

PMID- 23975189
TI  - Nanolithography: Painting with block copolymers.

PMID- 23975190
TI  - Sequential FISH allows the determination of the segregation outcome and the
      presence of numerical anomalies in spermatozoa from a t(1;8;2)(q42;p21;p15)
      carrier.
AB  - PURPOSE: To find out the meiotic segregation behaviour of the
      t(1;8;2)(q42;p21;p15), to evaluate the occurrence of interchromosomal effects,
      and to determine whether there is an accumulation of unbalanced products in
      aneuploid/diploid gametes. METHODS: A sequential FISH protocol based on two
      successive hybridization rounds over the same spermatozoa was performed to
      determine the segregation outcome of the rearranged chromosomes. The presence of
      numerical abnormalities for 13, 18, 21, X and Y was also evaluated by sperm FISH.
      Those aneuploid/diploid gametes were subsequently relocalized and analyzed for
      their segregation content through additional hybridization rounds. RESULTS: The
      segregation pattern observed reported a very low production of normal/balanced
      gametes (11.7 %). Significant increased frequencies of diploidies and disomies
      for chromosomes X/Y and 18 were detected (p < 0.001). Aneuploid and diploid
      spermatozoa displayed significant increases of 5:1, 6:0 and other unexpected
      disjunction modes (p < 0.001). CONCLUSIONS: The strategy developed in this study
      is a reliable new approach to establish the full segregation pattern of complex
      chromosome rearrangements (CCR). Results corroborate the low number of
      normal/balanced spermatozoa produced by CCR carriers and support previous
      findings regarding an altered segregation pattern in gametes with numerical
      abnormalities. Altogether this confirms the importance of PGD as a tool to
      prevent the transmission of chromosomal abnormalities to the offspring in CCR
      patients.

PMID- 23975191
TI  - TNF-alpha haplotype association with polycystic ovary syndrome - a South Indian
      study.
AB  - BACKGROUND: Tumor Necrosis Factor Alpha (TNF-alpha), is a proinflammatory
      cytokine in the pathogenesis of Polycystic Ovary Syndrome (PCOS). In order to
      investigate the role of rs1800629 and rs1799964 polymorphisms in relation to
      anthropometric measures, family history of complex diseases, diet and clinical
      features, we performed a case control study in PCOS women from South India.
      METHODS: A total of 589 samples comprising of 283 patients and 306 controls were
      enrolled in the present study. Patients were selected based on Rotterdam criteria
      and ultrasound scanned normal women were selected as controls. Following
      extraction of DNA, genotyping for rs1800629 and rs1799964 was performed by
      polymerase chain reaction using tetra primers and PCR-RFLP respectively. RESULTS:
      The distribution of genotypes for rs1799964 was significantly different between
      the groups (p = 0.001), however it was not for rs1800629. Haplotype analysis
      revealed a significant difference between patients and controls. The predisposing
      and protective role of haplotype with mutant allele at both loci (combination 3)
      and haplotype with mutant allele at either loci was reflected by the over
      representation of combination 3 in patients and combination 2 in controls
      respectively. In addition, rs1799964 showed an association with dietary habit,
      clinical hyperandrogenism and AAO. The modifying role of TT genotype on age at
      onset was noted in quartile analysis. CONCLUSION: Replicative studies on the
      influence of TNF-alpha polymorphism in different ethnic groups may identify the
      potentiality of these polymorphisms as markers of inflammation and in turn may
      help the clinicians for the better management of the condition.

PMID- 23975193
TI  - Retraction note to: Can fresh embryo transfers be replaced by cryopreserved
      thawed embryo transfers in assisted reproductive cycles? A randomized controlled
      trial.
AB  - This article has been retracted at the request of the Editor and the ASRM
      Publications Committee, based on the results of an investigation which found
      serious methodological flaws in the study.

PMID- 23975192
TI  - From the bench to bedside to babies: translational medicine made possible by
      funding multidisciplinary team science.
AB  - PURPOSE: In 2005, The National Institutes of Health (NIH) called upon the
      scientific community to identify the most intractable problems in science and
      medicine and describe how we would solve these problems using teams. METHODS: Our
      group was one of 8 research communities awarded an 'interdisciplinary research
      consortium (IRC) grant.' Using the infrastructure of this large, multi-institute
      grant and a team science approach, we set out to solve the problem of fertility
      loss in young female cancer patients-work that was not easily funded through
      other mechanisms. RESULTS: The word 'oncofertility' was coined specifically for
      the IRC to reflect the intimate partnership between oncology care and fertility
      care for these patients-two disciplines that would no longer function at arms'
      length, but as an integrated unit. Catalyzed by the IRC funding mechanism,
      interdisciplinary teams worked together in unique ways to create a 'bench to
      bedside to baby' outcome. CONCLUSIONS: The grant has now ended, and remarkably,
      so have the most intractable parts of the original problem. As we look back on
      what worked and look forward to tackling the next set of fertility-related
      questions, we are confident that this very special NIH funding mechanism made a
      meaningful difference in the lives of women and their future children. NIH and
      the public would be well-served by supporting clinical problem-based,
      multidisciplinary team science approaches to catalyze fundamental biomedical
      breakthroughs and create new intellectual environments in which changes in
      clinical practice and standard of care can be implemented.

PMID- 23975194
TI  - A modular framework for gene set analysis integrating multilevel omics data.
AB  - Modern high-throughput methods allow the investigation of biological functions
      across multiple 'omics' levels. Levels include mRNA and protein expression
      profiling as well as additional knowledge on, for example, DNA methylation and
      microRNA regulation. The reason for this interest in multi-omics is that actual
      cellular responses to different conditions are best explained mechanistically
      when taking all omics levels into account. To map gene products to their
      biological functions, public ontologies like Gene Ontology are commonly used.
      Many methods have been developed to identify terms in an ontology,
      overrepresented within a set of genes. However, these methods are not able to
      appropriately deal with any combination of several data types. Here, we propose a
      new method to analyse integrated data across multiple omics-levels to
      simultaneously assess their biological meaning. We developed a model-based
      Bayesian method for inferring interpretable term probabilities in a modular
      framework. Our Multi-level ONtology Analysis (MONA) algorithm performed
      significantly better than conventional analyses of individual levels and yields
      best results even for sophisticated models including mRNA fine-tuning by
      microRNAs. The MONA framework is flexible enough to allow for different
      underlying regulatory motifs or ontologies. It is ready-to-use for applied
      researchers and is available as a standalone application from
      http://icb.helmholtz-muenchen.de/mona. 

PMID- 23975195
TI  - A signature motif mediating selective interactions of BCL11A with the NR2E/F
      subfamily of orphan nuclear receptors.
AB  - Despite their physiological importance, selective interactions between nuclear
      receptors (NRs) and their cofactors are poorly understood. Here, we describe a
      novel signature motif (F/YSXXLXXL/Y) in the developmental regulator BCL11A that
      facilitates its selective interaction with members of the NR2E/F subfamily. Two
      copies of this motif (named here as RID1 and RID2) permit BCL11A to bind COUP-TFs
      (NR2F1;NR2F2;NR2F6) and Tailless/TLX (NR2E1), whereas RID1, but not RID2, binds
      PNR (NR2E3). We confirmed the existence of endogenous BCL11A/TLX complexes in
      mouse cortex tissue. No interactions of RID1 and RID2 with 20 other ligand
      binding domains from different NR subtypes were observed. We show that RID1 and
      RID2 are required for BCL11A-mediated repression of endogenous gamma-globin gene
      and the regulatory non-coding transcript Bgl3, and we identify COUP-TFII binding
      sites within the Bgl3 locus. In addition to their importance for BCL11A function,
      we show that F/YSXXLXXL/Y motifs are conserved in other NR cofactors. A single
      FSXXLXXL motif in the NR-binding SET domain protein NSD1 facilitates its
      interactions with the NR2E/F subfamily. However, the NSD1 motif incorporates
      features of both LXXLL and FSXXLXXL motifs, giving it a distinct NR-binding
      pattern in contrast to other cofactors. In summary, our results provide new
      insights into the selectivity of NR/cofactor complex formation. 

PMID- 23975196
TI  - Structural basis for Z-DNA binding and stabilization by the zebrafish Z-DNA
      dependent protein kinase PKZ.
AB  - The RNA-dependent protein kinase PKR plays a central role in the antiviral
      defense of vertebrates by shutting down protein translation upon detection of
      viral dsRNA in the cytoplasm. In some teleost fish, PKZ, a homolog of PKR,
      performs the same function, but surprisingly, instead of dsRNA binding domains,
      it harbors two Z-DNA/Z-RNA-binding domains belonging to the Zalpha domain family.
      Zalpha domains have also been found in other proteins, which have key roles in
      the regulation of interferon responses such as ADAR1 and DNA-dependent activator
      of IFN-regulatory factors (DAI) and in viral proteins involved in immune response
      evasion such as the poxviral E3L and the Cyprinid Herpesvirus 3 ORF112. The
      underlying mechanism of nucleic acids binding and stabilization by Zalpha domains
      is still unclear. Here, we present two crystal structures of the zebrafish PKZ
      Zalpha domain (DrZalpha(PKZ)) in alternatively organized complexes with a (CG)6
      DNA oligonucleotide at 2 and 1.8 A resolution. These structures reveal novel
      aspects of the Zalpha interaction with DNA, and they give insights on the
      arrangement of multiple Zalpha domains on DNA helices longer than the minimal
      binding site. 

PMID- 23975197
TI  - Elucidating the evolutionary conserved DNA-binding specificities of WRKY
      transcription factors by molecular dynamics and in vitro binding assays.
AB  - WRKY transcription factors constitute a large protein family in plants that is
      involved in the regulation of developmental processes and responses to biotic or
      abiotic stimuli. The question arises how stimulus-specific responses are mediated
      given that the highly conserved WRKY DNA-binding domain (DBD) exclusively
      recognizes the 'TTGACY' W-box consensus. We speculated that the W-box consensus
      might be more degenerate and yet undetected differences in the W-box consensus of
      WRKYs of different evolutionary descent exist. The phylogenetic analysis of WRKY
      DBDs suggests that they evolved from an ancestral group IIc-like WRKY early in
      the eukaryote lineage. A direct descent of group IIc WRKYs supports a
      monophyletic origin of all other group II and III WRKYs from group I by loss of
      an N-terminal DBD. Group I WRKYs are of paraphyletic descent and evolved multiple
      times independently. By homology modeling, molecular dynamics simulations and in
      vitro DNA-protein interaction-enzyme-linked immunosorbent assay with AtWRKY50
      (IIc), AtWRKY33 (I) and AtWRKY11 (IId) DBDs, we revealed differences in DNA
      binding specificities. Our data imply that other components are essentially
      required besides the W-box-specific binding to DNA to facilitate a stimulus
      specific WRKY function. 

PMID- 23975198
TI  - Observation of unpaired substrate DNA in the flap endonuclease-1 active site.
AB  - The structure- and strand-specific phosphodiesterase flap endonuclease-1 (FEN1),
      the prototypical 5'-nuclease, catalyzes the essential removal of 5'-single
      stranded flaps during replication and repair. FEN1 achieves this by selectively
      catalyzing hydrolysis one nucleotide into the duplex region of substrates, always
      targeting the 5'-strand. This specificity is proposed to arise by unpairing the
      5'-end of duplex to permit the scissile phosphate diester to contact catalytic
      divalent metal ions. Providing the first direct evidence for this, we detected
      changes induced by human FEN1 (hFEN1) in the low-energy CD spectra and
      fluorescence lifetimes of 2-aminopurine in substrates and products that were
      indicative of unpairing. Divalent metal ions were essential for unpairing.
      However, although 5'-nuclease superfamily-conserved active-site residues K93 and
      R100 were required to produce unpaired product, they were not necessary to unpair
      substrates. Nevertheless, a unique arrangement of protein residues around the
      unpaired DNA was detected only with wild-type protein, suggesting a cooperative
      assembly of active-site residues that may be triggered by unpaired DNA. The
      general principles of FEN1 strand and reaction-site selection, which depend on
      the ability of juxtaposed divalent metal ions to unpair the end of duplex DNA,
      may also apply more widely to other structure- and strand-specific nucleases. 

PMID- 23975199
TI  - Heterogeneous staining: a tool for studies of how fluorescent dyes affect the
      physical properties of DNA.
AB  - The commonly used fluorescent dye YOYO-1 (YOYO) has, using bulk techniques, been
      demonstrated to stain DNA heterogeneously at substoichiometric concentrations. We
      here, using nanofluidic channels and fluorescence microscopy, investigate the
      heterogeneous staining on the single DNA molecule level and demonstrate that the
      dye distribution is continuous. The equilibration of YOYO on DNA is extremely
      slow but can be accelerated by increasing the ionic strength and/or the
      temperature. Furthermore, we demonstrate how to use the heterogeneous staining as
      a tool for detailed and time-efficient studies of how fluorescent dyes affect the
      physical properties of DNA. We show that the relative increase in extension of
      DNA with increasing amount of YOYO bound is higher at low ionic strengths and
      also extrapolate the extension of native DNA. Our study reveals important
      information on how YOYO affects the physical properties of DNA, but it also has
      broader applications. First, it reveals how cationic intercalators, such as
      potential DNA drugs, affect DNA under strong confinement. Second, the strategy of
      using heterogeneous staining is of general use for single molecule studies of DNA
      interacting with proteins or ligands. 

PMID- 23975200
TI  - Crystal structure of the DdrB/ssDNA complex from Deinococcus radiodurans reveals
      a DNA binding surface involving higher-order oligomeric states.
AB  - The ability of Deinococcus radiodurans to recover from extensive DNA damage is
      due in part to its ability to efficiently repair its genome, even following
      severe fragmentation by hundreds of double-strand breaks. The single-strand
      annealing pathway plays an important role early during the recovery process,
      making use of a protein, DdrB, shown to greatly stimulate ssDNA annealing. Here,
      we report the structure of DdrB bound to ssDNA to 2.3 A. Pentameric DdrB was
      found to assemble into higher-order structures that coat ssDNA. To gain further
      mechanistic insight into the protein's function, a number of point mutants were
      generated altering both DNA binding and higher order oligomerization. This work
      not only identifies higher-order DdrB associations but also suggests the presence
      of an extended DNA binding surface running along the 'top' surface of a DdrB
      pentamer and continuing down between two individual subunits of the ring
      structure. Together this work sheds new insight into possible mechanisms for DdrB
      function in which higher-order assemblies of DdrB pentamers assist in the pairing
      of complementary ssDNA using an extended DNA binding surface. 

PMID- 23975201
TI  - Homology-mediated end-capping as a primary step of sister chromatid fusion in the
      breakage-fusion-bridge cycles.
AB  - Breakage-fusion-bridge (BFB) cycle is a series of chromosome breaks and
      duplications that could lead to the increased copy number of a genomic segment
      (gene amplification). A critical step of BFB cycles leading to gene amplification
      is a palindromic fusion of sister chromatids following the rupture of a dicentric
      chromosome during mitosis. It is currently unknown how sister chromatid fusion is
      produced from a mitotic break. To delineate the process, we took an integrated
      genomic, cytogenetic and molecular approach for the recurrent MCL1 amplicon at
      chromosome 1 in human tumor cells. A newly developed next-generation sequencing
      based approach identified a cluster of palindromic fusions within the amplicon at
      ~50-kb intervals, indicating a series of breaks and fusions by BFB cycles. The
      physical location of the amplicon (at the end of a broken chromosome) further
      indicated BFB cycles as underlying processes. Three palindromic fusions were
      mediated by the homologies between two nearby inverted Alu repeats, whereas the
      other two fusions exhibited microhomology-mediated events. Such breakpoint
      sequences indicate that homology-mediated fold-back capping of broken ends
      followed by DNA replication is an underlying mechanism of sister chromatid
      fusion. Our results elucidate nucleotide-level events during BFB cycles and end
      processing for naturally occurring mitotic breaks. 

PMID- 23975202
TI  - Age-dependent changes in the functions and compositions of photosynthetic
      complexes in the thylakoid membranes of Arabidopsis thaliana.
AB  - Photosynthetic complexes in the thylakoid membrane of plant leaves primarily
      function as energy-harvesting machinery during the growth period. However, leaves
      undergo developmental and functional transitions along aging and, at the
      senescence stage, these complexes become major sources for nutrients to be
      remobilized to other organs such as developing seeds. Here, we investigated age
      dependent changes in the functions and compositions of photosynthetic complexes
      during natural leaf senescence in Arabidopsis thaliana. We found that Chl a/b
      ratios decreased during the natural leaf senescence along with decrease of the
      total chlorophyll content. The photosynthetic parameters measured by the
      chlorophyll fluorescence, photochemical efficiency (F v/F m) of photosystem II,
      non-photochemical quenching, and the electron transfer rate, showed a
      differential decline in the senescing part of the leaves. The CO2 assimilation
      rate and the activity of PSI activity measured from whole senescing leaves
      remained relatively intact until 28 days of leaf age but declined sharply
      thereafter. Examination of the behaviors of the individual components in the
      photosynthetic complex showed that the components on the whole are decreased, but
      again showed differential decline during leaf senescence. Notably, D1, a PSII
      reaction center protein, was almost not present but PsaA/B, a PSI reaction center
      protein is still remained at the senescence stage. Taken together, our results
      indicate that the compositions and structures of the photosynthetic complexes are
      differentially utilized at different stages of leaf, but the most dramatic change
      was observed at the senescence stage, possibly to comply with the physiological
      states of the senescence process. 

PMID- 23975203
TI  - Proton transport facilitating water-oxidation: the role of second sphere ligands
      surrounding the catalytic metal cluster.
AB  - The ability of PSII to extract electrons from water, with molecular oxygen as a
      by-product, is a remarkable biochemical and evolutionary innovation. From an
      evolutionary perspective, the invention of PSII approximately 2.7 Ga led to the
      accelerated accumulation of biomass in the biosphere and the accumulation of
      oxygen in the atmosphere, a combination that allowed for the evolution of a much
      more complex and extensive biosphere than would otherwise have been possible.
      From the biochemical and enzymatic perspective, PSII is remarkable because of the
      thermodynamic and kinetic obstacles that needed to have been overcome to oxidize
      water as the ultimate photosynthetic electron donor. This article focuses on how
      proton release is an integral part of how these kinetic and thermodynamic
      obstacles have been overcome: the sequential removal of protons from the active
      site of H2O-oxidation facilitates the multistep oxidation of the substrate water
      at the Mn4CaOx, the catalytic heart of the H2O-oxidation reaction. As noted
      previously, the facilitated deprotonation of the Mn4CaOx cluster exerts a redox
      leveling function preventing the accumulation of excess positive charge on the
      cluster, which might otherwise hinder the already energetically difficult
      oxidation of water. Using recent results, including the characteristics of site
      directed mutants, the role of the second sphere of amino acid ligands and the
      associated network of water molecules surrounding the Mn4CaOx is discussed in
      relation to proton transport in other systems. In addition to the redox-leveling
      function, a trapping function is assigned to the proton release step occurring
      immediately prior to the dioxygen chemistry. This trapping appears to involve a
      yet-to-be clarified gating mechanism that facilitates to coordinated release of a
      proton from the neighborhood of the active site thereby insuring that the
      backward charge-recombination reaction does not out-compete the forward reaction
      of dioxygen chemistry during this final step of H2O-oxidation.

PMID- 23975204
TI  - SHARP: genome-scale identification of gene-protein-reaction associations in
      cyanobacteria.
AB  - Genome scale metabolic model provides an overview of an organism's metabolic
      capability. These genome-specific metabolic reconstructions are based on
      identification of gene to protein to reaction (GPR) associations and, in turn, on
      homology with annotated genes from other organisms. Cyanobacteria are
      photosynthetic prokaryotes which have diverged appreciably from their
      nonphotosynthetic counterparts. They also show significant evolutionary
      divergence from plants, which are well studied for their photosynthetic
      apparatus. We argue that context-specific sequence and domain similarity can add
      to the repertoire of the GPR associations and significantly expand our view of
      the metabolic capability of cyanobacteria. We took an approach that combines the
      results of context-specific sequence-to-sequence similarity search with those of
      sequence-to-profile searches. We employ PSI-BLAST for the former, and CDD, Pfam,
      and COG for the latter. An optimization algorithm was devised to arrive at a
      weighting scheme to combine the different evidences with KEGG-annotated GPRs as
      training data. We present the algorithm in the form of software "Systematic,
      Homology-based Automated Re-annotation for Prokaryotes (SHARP)." We predicted
      3,781 new GPR associations for the 10 prokaryotes considered of which eight are
      cyanobacteria species. These new GPR associations fall in several metabolic
      pathways and were used to annotate 7,718 gaps in the metabolic network. These new
      annotations led to discovery of several pathways that may be active and thereby
      providing new directions for metabolic engineering of these species for
      production of useful products. Metabolic model developed on such a reconstructed
      network is likely to give better phenotypic predictions. 

PMID- 23975205
TI  - Isolation of monomeric photosystem II that retains the subunit PsbS.
AB  - Photosystem II has been purified from a transplastomic strain of Nicotiana
      tabacum according to two different protocols. Using the procedure described in
      Piano et al. (Photosynth Res 106:221-226, 2010) it was possible to isolate highly
      active PSII composed of monomers and dimers but depleted in their PsbS protein
      content. A "milder" procedure than the protocol reported by Fey et al. (Biochim
      Biophys Acta 1777:1501-1509, 2008) led to almost exclusively monomeric PSII
      complexes which in part still bind the PsbS protein. This finding might support a
      role for PSII monomers in higher plants. 

PMID- 23975206
TI  - Conclusions about the benefits and risks associated with iron supplementation for
      anaemia prevention and control for preschoolers are limited by poor study
      quality.

PMID- 23975207
TI  - Lower target oxygen saturation levels in preterm infants are associated with
      increased mortality and decreased rates of retinopathy of prematurity.

PMID- 23975208
TI  - Using effort-reward imbalance theory to understand high rates of depression and
      anxiety among clergy.
AB  - The clergy occupation is unique in its combination of role strains and higher
      calling, putting clergy mental health at risk. We surveyed all United Methodist
      clergy in North Carolina, and 95% (n = 1,726) responded, with 38% responding via
      phone interview. We compared clergy phone interview depression rates, assessed
      using the Patient Health Questionnaire (PHQ-9), to those of in-person interviews
      in a representative United States sample that also used the PHQ-9. The clergy
      depression prevalence was 8.7%, significantly higher than the 5.5% rate of the
      national sample. We used logistic regression to explain depression, and also
      anxiety, assessed using the Hospital Anxiety and Depression Scale. As
      hypothesized by effort-reward imbalance theory, several extrinsic demands (job
      stress, life unpredictability) and intrinsic demands (guilt about not doing
      enough work, doubting one's call to ministry) significantly predicted depression
      and anxiety, as did rewards such as ministry satisfaction and lack of financial
      stress. The high rate of clergy depression signals the need for preventive
      policies and programs for clergy. The extrinsic and intrinsic demands and rewards
      suggest specific actions to improve clergy mental health.

PMID- 23975209
TI  - Parents of older at-risk youth: a retention challenge for preventive
      intervention.
AB  - We examined data from 162 families who participated in the prevention program
      Parents and Youth with Schools, which targeted at-risk high school youth and
      parents, to understand parent retention in the 15-session Parents as Partners
      program. We obtained reports from youth, parents and parent interventionists,
      which included both time-invariant and time-varying data regarding demographic
      factors; parent, youth and family characteristics; and parents' response to
      intervention. Utilizing event history analysis, we examined data sequentially in
      order to determine those variables that predicted continued parent attendance. In
      the model examining all areas simultaneously, the predictors of parent retention
      across the full program were parent minority status and age, teen anger and
      parent-teen conflict over school attendance, as well as parents' reports of group
      support and interventionists' report of parents' commitment. Overall, the
      analyses indicated that participants' characteristics, as well as their
      measureable response to the intervention, can alert researchers to potential
      program disengagement. Monitoring indicators of disengagement will help
      researchers focus resources early in the intervention process in order to
      maximize parent attendance and increase the success of prevention programs. 

PMID- 23975210
TI  - WITHDRAWN:A Validation Study of the International Consensus Diagnostic Criteria
      for Neuroleptic Malignant Syndrome.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 23975211
TI  - Psychiatry residents' perception of public/community psychiatry fellowship
      training.
AB  - In order to improve recruitment into public/community psychiatry fellowships, a
      survey was administered to understand psychiatry residents' perception of
      benefits and obstacles to fellowship training. Using standard statistical
      methods, the responses of those residents who indicated interest in
      public/community psychiatry training were compared to those who were not.
      Residents who were interested in public/community psychiatry fellowships were
      earlier in their training. These same residents gave higher endorsements to items
      related to quality, location and flexibility of training program, recommendation
      of colleagues, opportunities for health policy training and networking as
      compared to residents who were not interested in pursuing a public/community.
      Those results attained statistical significance while philosophical approaches
      including emphasis on recovery and tailoring specific training experiences
      approached significance. Psychiatric residents appear to start residency training
      with some interest in public/community psychiatry and this interest can be
      nurtured if public/community psychiatry is emphasized during training. 

PMID- 23975212
TI  - Inverse correlation between vascular calcification and bone mineral density in
      human immunodeficiency virus-infected patients.
AB  - HIV-infected individuals suffer from accelerated aging, which manifests as
      premature cardiovascular and bone disease. However, little is known of the
      association of these two disorders in the HIV population. Our objective was to
      investigate the association between a marker of atherosclerosis (coronary artery
      calcium [CAC]) and low bone mineral density (BMD) in a cross-sectional cohort of
      HIV-infected patients. The study was conducted at the University of Modena and
      Reggio Emilia, Italy. A total of 636 consecutive middle-aged, HIV-infected
      subjects were recruited between January 2006 and December 2010. All patients
      underwent CAC and BMD assessment. Patients were categorized according to a CAC
      score <100 or >100 units based on previous literature that identified this cut
      point as a marker of increased risk. Low femoral and lumbar spine BMD was defined
      as <25th percentile value for the study cohort. Logistic regression and bootstrap
      analysis were used to assess the independent association between CAC and BMD. The
      main outcome measure was a CAC score >100. Patients with CAC > 100 were older and
      more likely to be men, diabetic, and overweight. Patients with CAC < 100 had
      better renal function and a lower cardiovascular risk profile. After adjusting
      for age, sex, traditional and HIV-specific risk factors, vitamin D level, and PTH
      level, there was a significant association between CAC > 100 and low BMD for the
      femur (OR = 2.33, 95 % CI 1.09-4.99; p = 0.02) but not for the spine. Bootstrap
      analyses confirmed these findings. In summary, CAC was independently associated
      with low femoral BMD in HIV-infected patients. Future studies should test whether
      therapies that attenuate cardiovascular risk in HIV favorably impact bone health.

PMID- 23975213
TI  - Association between aortic calcification and the risk of osteoporosis in a
      chinese cohort: the Chongqing osteoporosis study.
AB  - The aim of this study was to examine the relationship between aortic
      calcification (AC) and the risk of osteoporosis for a community of residents in
      China. We conducted a 5-year prospective study on 1,729 Chinese elderly subjects.
      An AC scale (ACS) was determined semiquantitatively from baseline lateral
      radiographs of the lumbar spine. Dual-energy X-ray absorptiometry was used to
      determine bone mineral density (BMD). Only subjects who completed the study were
      included in the final analysis; 432 subjects (25.0 %) developed osteoporosis. The
      BMD of vertebrae, femoral neck, and the total hip in the Q4 quartile of the ACS
      (ACS > 6) was lower when compared with the Q1 quartile (ACS = 0, p < 0.05). Cox
      proportional hazards model analysis showed that ACS (Q4), BMD, CTX, current
      smoking, and daily drinking were associated with increased risk of osteoporosis.
      A higher ACS was associated with an increased risk of osteoporosis in both women
      and men. The present study found that AC carried a higher risk of osteoporosis.

PMID- 23975214
TI  - IP-10/CXCL10 and MIG/CXCL9 as novel markers for the diagnosis of lymphoma
      associated hemophagocytic syndrome.
AB  - Lymphoma-associated hemophagocytic syndrome (LAHS) is a serious disorder, and its
      early diagnosis and treatment with appropriate chemotherapy are very important.
      However, reliable markers for early diagnosis of LAHS have not been identified.
      We screened serum cytokines using a newly introduced assay system, cytometric
      bead array (CBA), and identified interferon-inducible protein 10 (IP-10)/CXCL10
      and monokine induced by interferon gamma (MIG)/CXCL9 as useful markers. Serum
      concentrations of IP-10 and MIG at the time of LAHS diagnosis were greater than
      500 and 5,000 pg/ml, respectively. The sensitivity and specificity for LAHS
      diagnosis were 100 and 95 %, respectively, when we set the above values as the
      cut-off levels. Serum levels of these two chemokines were already elevated at the
      time of admission and significantly decreased after successful treatment,
      indicating their usefulness for both the diagnosis and therapeutic outcomes for
      LAHS. IP-10 and MIG were also useful in distinguishing severe from moderate/mild
      LAHS, and B-cell-type LAHS from T-cell/natural killer cell-type LAHS.
      Furthermore, IP-10 and MIG were of use to distinguish LAHS from sepsis in
      patients with hematologic malignancies. Rapid measurement of IP-10 and MIG by CBA
      appeared to be important for early diagnosis and treatment of LAHS.

PMID- 23975215
TI  - Comparative analysis of mandibular anatomical variations between panoramic
      radiography and cone beam computed tomography.
AB  - PURPOSE: The objective of this study is to compare the ability of panoramic
      radiography and cone beam computed tomography (CBCT) in detecting anatomical
      variations of the mandibular canal and mental foramen. METHODS: One hundred
      twenty-seven preoperative panoramic and CBCT images were evaluated. Two oral and
      maxillofacial radiologists investigated the presence of bifid mandibular canals
      and/or additional mental foramina on the right, left, or both sides of the
      mandible. Intra- and interobserver reliability was determined using Cohen's kappa
      coefficient. McNemar's test compared the prevalence of mandibular anatomical
      variations between panoramic radiography and CBCT. The significance level was set
      at 0.05. RESULTS: Additional mental foramen and bifid mandibular canal were
      detected in 1.2 and 7.4 % of the panoramic radiographs and 7.4 and 9.8 % of the
      CBCT images, respectively. The incidence of anatomical variations on the
      mandibular canal was not significantly different between both imaging modalities
      (P > 0.05). CONCLUSIONS: Although CBCT provides better viewing of anatomical
      structures, including location, shape, and relationship with the surrounding
      area, panoramic radiography is a conventional imaging modality that can be used
      in the study of the bifid mandibular canals.

PMID- 23975216
TI  - [PREFERE--the German prostatic cancer study].

PMID- 23975217
TI  - [PREFERE--the German prostatic cancer study].

PMID- 23975218
TI  - [Muscle invasive bladder cancer after radical cystectomy. Prognostic factors of
      adjuvant chemotherapy].
AB  - BACKGROUND: The indications to administer adjuvant systemic chemotherapy to
      patients with urothelial carcinoma of the bladder who underwent radical
      cystectomy is discussed controversially and all international guidelines are very
      restrictive with regard to its recommendation for routine daily practice due to
      the low scientific evidence concerning its therapeutic benefit. Currently,
      adjuvant systemic chemotherapy should be preferably administered within clinical
      trials. In the daily routine adjuvant treatment might be given in patients with
      lymph node positive disease. Clinical, pathohistological and molecular biomarkers
      which might be associated with a positive or negative treatment response have
      been evaluated sparsely in the past. RESULTS: The presence of
      hemangiosis/lymphangiosis carcinomatosa and/or extranodal expansion in patients
      with lymph node metastases appears to be associated with a poor outcome. The
      markers ERCC-1, XAF and anti-apoptotic proteins of the Bcl-2 family seem to
      represent the most promising biomarkers associated with response to adjuvant
      cisplatin-based chemotherapy.

PMID- 23975219
TI  - [Influence of obesity on urological malignancies].
AB  - BACKGROUND: Overweight presents a growing problem in our society; therefore,
      there is an increasing interest to understand the influence of obesity on
      urological forms of cancer. AIM: In prostate cancer the development of a more
      aggressive phenotype seems to correlate with obesity. In renal cell cancer (RCC)
      obesity is both, a risk factor for occurrence -and is also associated with an
      improved tumour-specific survival in patients with organ-confined disease
      following kidney surgery as well as overall survival of patients with advanced
      disease receiving VEGF(R)-targeted treatment. In contrast, even though an
      association between body mass index (BMI) and bladder cancer has been described
      the role of obesity in bladder cancer remains largely unclear as published data
      are contradictory. RESULTS: An update on currently available data focusing on the
      relationship between obesity and genitourinary malignancies is given in this
      review; however, basic research which is necessary to define the biological and
      metabolic effects associated with obesity and which might affect the development
      and progression of urological cancers, is indicated.

PMID- 23975220
TI  - [Biomarker docetaxel-based chemotherapy].
AB  - In the prostate-specific antigen (PSA) era, prostate cancer is detected at more
      local stages. Nevertheless, depending on e.g. the differentiation stage there is
      recurrent disease in 10-40% of the cases with the need of further treatment. Once
      hormonal therapy has been initiated the disease can progress to the castration
      resistant stage and the question of chemotherapy arises. At this stage PSA
      sensitivity decreases. Although there is a significant improvement in survival
      only about 50% of the patients benefit from chemotherapy. Recently several new
      drugs have or will soon be approved in the setting of castration-resistant
      prostate cancer (CRPCA). Several prognostic molecular markers have been
      investigated. In this review some objective important biomarkers, proteins and
      targets will be presented. 

PMID- 23975221
TI  - Pachydictyols B and C: new diterpenes from Dictyota dichotoma Hudson.
AB  - Two new diterpenoids, pachydictyol B (1a/1b) and C (2), were isolated from the
      dichloromethane extract of the marine brown alga, Dictyota dichotoma, collected
      from the Red Sea coast of Egypt, along with the known metabolites, pachydictyol A
      (3a), dictyol E (4), cis-africanan-1alpha-ol (5a), fucosterol (6),
      tetrahydrothiophen-1,1-dioxide and poly-beta-hydroxybutyric acid. GC-MS analysis
      of the nonpolar fractions also indicated the presence of beta-bourbonene and
      nonanal, along with three hydrocarbons and five fatty acids or their simple
      derivatives, respectively. GC-MS analysis of the unsaponifiable algal petroleum
      ether extract revealed the presence of a further eight compounds, among them
      2,2,6,7-tetramethyl-10-oxatricyclo[4.3.0.1(1,7)]decan-5-one (7), N-(4-bromo-n
      butyl)-pipe ridin-2-one (8) and tert-hexadecanethiol. Structures 1-6 were
      assigned by 1D and 2D NMR, mass spectra (EI, CI, HREI and HRESI) and by
      comparison with data from related structures. The crude algal extract was
      potently active against the breast carcinoma tumor cell line, MCF7 (IC50 = 0.6 ug
      mL-1); pachydictyol B (1a) and dictyol E (4) showed weak antimicrobial
      properties, and the other compounds were inactive. Pachydictyols B (1a) and C (2)
      demonstrated a weak and unselective cytotoxicity against twelve human tumor cell
      lines with a mean IC50 of >30.0 uM.

PMID- 23975222
TI  - Platelet activation in essential hypertension during exercise: pre- and post
      treatment changes with an angiotensin II receptor blocker.
AB  - BACKGROUND: Acute exercise may exert deleterious effects on the cardiovascular
      system through a variety of pathophysiological mechanisms, including increased
      platelet activation. However, the degree of exercise-induced platelet activation
      in untreated hypertensive (UH) individuals as compared with normotensive (NT)
      individuals has yet to be established. Furthermore, the effect of
      antihypertensive treatment on exercise-induced platelet activation in essential
      hypertension (EH) remains unknown. METHODS: Study 1 consisted of 30 UH and 15 NT
      subjects. UH subjects who received treatment were included in study 2 and were
      followed-up after a 3-month treatment period with an angiotensin II receptor
      blocker (ARB; valsartan). Circulating monocyte-platelet aggregates (MPA) and
      platelet P-selectin were measured as platelet activation markers at baseline,
      immediately after a treadmill exercise test, and 10, 30, and 90 minutes later.
      RESULTS: Maximal platelet activation was observed at 10 minutes after peak
      exercise in both groups. In UH subjects, MPA levels remained increased at 30
      minutes after peak exercise, despite BP fall to baseline levels. MPA levels were
      significantly higher in UH subjects than NT subjects at maximal exercise and at
      10 and 30 minutes of recovery. Post-treatment MPA levels increased significantly
      only at 10 minutes into recovery and were similar to those of NT subjects.
      CONCLUSIONS: Acute high-intensity exercise exaggerates platelet activation in
      untreated patients with EH compared with NT individuals. Angiotensin II receptor
      blockade with adequate BP control greatly improves exercise-induced platelet
      activation in EH. Further studies are needed to clarify whether this phenomenon
      depends purely on BP lowering or benefits also from the pleiotropic effects of
      ARBs.

PMID- 23975223
TI  - Plzf as a candidate gene predisposing the spontaneously hypertensive rat to
      hypertension, left ventricular hypertrophy, and interstitial fibrosis.
AB  - BACKGROUND: The spontaneously hypertensive rat (SHR) is the most widely used
      model of essential hypertension and is susceptible to left ventricular
      hypertrophy (LVH) and myocardial fibrosis. Recently, a quantitative trait locus
      (QTL) that influences heart interstitial fibrosis was mapped to chromosome 8. Our
      aim was to dissect the genetic basis of this QTL(s) predisposing SHR to
      hypertension, LVH, and interstitial fibrosis. METHODS: Hemodynamic and
      histomorphometric analyses were performed in genetically defined SHR.PD-chr.8
      minimal congenic strain (PD5 subline) rats. RESULTS: The differential segment,
      genetically isolated within the PD5 subline, spans 788kb and contains 7 genes,
      including the promyelocytic leukemia zinc finger (Plzf) gene that has been
      implicated in hypertrophy and cardiac fibrosis. Mutant Plzf allele contains a
      2,964-bp deletion in intron 2. The PD5 congenic strain, when compared with the
      SHR, showed significantly reduced systolic blood pressure by approximately 15mm
      Hg (P = 0.002), amelioration of LVH (0.23+/-0.02 vs. 0.39+/-0.02g/100g body
      weight; P < 0.00001), and reduced interstitial fibrosis (17,478+/-1,035 vs.
      41,530+/-3,499 MUm(2); P < 0.0001). The extent of amelioration of LVH and
      interstitial fibrosis was disproportionate to blood pressure decrease in congenic
      rats, suggesting an important role for genetic factors. Cardiac expression of
      Plzf was significantly reduced in prehypertensive (8 and 21 days) congenic
      animals compared with controls. CONCLUSIONS: These results provide compelling
      evidence of a significant role for genetic factors in regulating blood pressure,
      LVH, and cardiac fibrosis and identify mutant Plzf as a prominent candidate gene.

PMID- 23975224
TI  - Gestational diabetes mellitus epigenetically affects genes predominantly involved
      in metabolic diseases.
AB  - Offspring exposed to gestational diabetes mellitus (GDM) have an increased risk
      for chronic diseases, and one promising mechanism for fetal metabolic programming
      is epigenetics. Therefore, we postulated that GDM exposure impacts the
      offspring's methylome and used an epigenomic approach to explore this hypothesis.
      Placenta and cord blood samples were obtained from 44 newborns, including 30
      exposed to GDM. Women were recruited at first trimester of pregnancy and followed
      until delivery. GDM was assessed after a 75-g oral glucose tolerance test at 24
      28 weeks of pregnancy. DNA methylation was measured at>485,000 CpG sites
      (Infinium HumanMethylation450 BeadChips). Ingenuity Pathway Analysis was
      conducted to identify metabolic pathways epigenetically affected by GDM. Our
      results showed that 3,271 and 3,758 genes in placenta and cord blood,
      respectively, were potentially differentially methylated between samples exposed
      or not to GDM (p-values down to 1 * 10(-06); none reached the genome-wide
      significance levels), with more than 25% (n = 1,029) being common to both
      tissues. Mean DNA methylation differences between groups were 5.7 +/- 3.2% and
      3.4 +/- 1.9% for placenta and cord blood, respectively. These genes were likely
      involved in the metabolic diseases pathway (up to 115 genes (11%), p-values for
      pathways = 1.9 * 10(-13)<p<4.0 * 10(-03); including diabetes mellitus p = 4.3 *
      10(-11)). Among the differentially methylated genes, 326 in placenta and 117 in
      cord blood were also associated with newborn weight. Our results therefore
      suggest that GDM has epigenetic effects on genes preferentially involved in the
      metabolic diseases pathway, with consequences on fetal growth and development,
      and provide supportive evidence that DNA methylation is involved in fetal
      metabolic programming.

PMID- 23975225
TI  - Affordability of cancer treatment for aging cancer patients in Singapore: an
      analysis of health, lifestyle, and financial burden.
AB  - BACKGROUND: With the expected rise in newly diagnosed cancer cases among the
      elderly in Singapore, the affordability of cancer treatments, particularly of
      targeted therapies, will be a growing concern for patients. This study examines
      the perspectives of aging cancer patients on the financial burden of their cancer
      treatments. METHODS: A single-center, prospective study was conducted in the
      largest ambulatory cancer center in Singapore. Older (50 years old and above)
      cancer patients receiving treatment were recruited. Patients completed three sets
      of self-reporting tools assessing their (a) demographics and lifestyles, (b)
      health-related quality of life, and (c) perceptions of cancer treatment costs.
      The association between targeted therapy utilities and their perceived financial
      burden was evaluated using a multivariable logistic regression. RESULTS: Five
      hundred and sixteen patients were included in the study. The majority of the
      respondents (69.6 %) were between 50 and 64 years old. The majority were
      Singaporeans (97.7 %), belonged to the ethnic Chinese group (88.4 %), and most
      were female (59.1 %). The users of targeted therapies were 2.92 times more likely
      to perceive that the amount of cash that they spent on cancer treatment was more
      than expected and 2.52 times more likely to have difficulty paying for cancer
      treatments. Fortunately, the majority of the respondents (70.6 %) found their
      existing financial schemes helpful in reducing the necessary out-of-pocket
      expenses. CONCLUSIONS: Although aging cancer patients feel that the financial
      schemes in Singapore have helped them tremendously, the general perception is
      that they require further help to offset their out-of-pocket expenses. This is
      especially true for users of targeted therapies and those who have a poorer
      health status.

PMID- 23975226
TI  - Pain and health-related quality of life in patients with advanced solid tumours
      and bone metastases: integrated results from three randomized, double-blind
      studies of denosumab and zoledronic acid.
AB  - PURPOSE: This analysis evaluated patient-reported outcomes and analgesic use in
      patients with bone metastases from solid tumours across three comparative studies
      of denosumab and zoledronic acid. METHODS: Pooled data were analysed from three
      identically designed double-blind phase III studies comparing subcutaneous
      denosumab 120 mg with intravenous zoledronic acid 4 mg monthly in patients with
      bone metastases from breast cancer (n = 2,046), castration-resistant prostate
      cancer (n = 1,901) or other solid tumours (n = 1,597). Pain severity, pain
      interference, health-related quality of life and analgesic use were quantified.
      RESULTS: At baseline, approximately half of patients had no/mild pain (53 %
      [1,386/2,620] denosumab; 50 % [1,297/2,578] zoledronic acid). Denosumab delayed
      onset of moderate/severe pain by 1.8 months (median, 6.5 vs 4.7 months; hazard
      ratio, 0.83; 95 % CI, 0.76-0.92; p < 0.001; 17 % risk reduction) and clinically
      meaningful increases in overall pain interference by 2.6 months (median, 10.3 vs
      7.7 months; hazard ratio, 0.83; 95 % CI, 0.75-0.92; p < 0.001; 17 % risk
      reduction) compared with zoledronic acid. Strong opioid use and worsening of
      health-related quality of life were less common with denosumab. CONCLUSIONS:
      Across three large studies of patients with advanced solid tumours and bone
      metastases, denosumab prevented progression of pain severity and pain
      interference more effectively than zoledronic acid.

PMID- 23975227
TI  - Hemophagocytic syndrome in children with acute monoblastic leukemia-another cause
      of fever of unknown origin.
AB  - PURPOSE: Intensification of antileukemic treatment and progress in supportive
      management have improved the survival rates of children with acute myeloid
      leukemia (AML). However, morbidity and early mortality in these patients are
      still very high, especially in children with acute monoblastic leukemia (AML FAB
      M5). Inflammatory syndromes complicating the management of these children after
      application of cytosine arabinoside and due to hyperleukocytosis at initial
      presentation have been reported. Hemophagocytic lymphohistiocytosis (HLH) has
      been described as a serious and life-threatening acute complication during
      treatment of different oncologic entities; however, data on HLH in children with
      AML FAB M5 are extremely rare. METHODS: A retrospective study of all children
      with AML FAB M5 treated at our institution between 1993 and 2013 was performed to
      describe the clinical characteristics of patients who developed an inflammatory
      syndrome with HLH during oncologic treatment. RESULTS: Three of 10 children
      developed an inflammatory syndrome with fever, elevation of C-reactive protein,
      hyperferritinemia, elevation of soluble interleukin-2, and hemophagocytosis
      during prolonged aplasia following the first cycle of chemotherapy not responding
      to broad-spectrum antibiotics. No infectious agents could be identified; the
      initial symptoms occurred 17, 18, and 28 days after diagnosis of AML,
      respectively. The children immediately responded to dexamethasone; however, the
      same syndrome was observed again after the second cycle of chemotherapy and, in
      one patient, also after the third cycle. CONCLUSIONS: Treating physicians should
      be aware of an inflammatory syndrome resembling HLH in children with monoblastic
      leukemia since this problem might extremely complicate management and supportive
      care of these children. The co-incidence of monoblastic leukemia with HLH might
      be explained by cytokines released from the monoblastic leukemic cells
      themselves.

PMID- 23975228
TI  - Oral status of patients submitted to autologous hematopoietic stem cell
      transplantation.
AB  - PURPOSE: Oral infection may be a source of bacteremia in patients undergoing
      hematopoietic stem cell transplant (HSCT). The aim of this study was to evaluate
      the relationship between patients with poor periodontal status and complications
      after HSCT. METHODS: A cohort of patients with hematological malignancies
      candidates for autologous HSCT was observed before and during the neutropenic
      phase of HSCT. A primary evaluation was performed before the HSCT procedure,
      including medical and socio-demographic data and physical examination (number of
      teeth and decayed, missing and filled teeth index (DMFT), oral mucosa, and full
      mouth periodontal assessment). During the neutropenic phase, data regarding the
      development of febrile neutropenia, bacteremia, and mucositis were also
      prospectively obtained. RESULTS: Forty-eight patients were included. The most
      common baseline disease was multiple myeloma (70 %). In the primary evaluations,
      the median DMFT was 13 (ranging 0-27), and periodontitis and gingivitis were
      present in 29 and 60 % of the patients, respectively. During the neutropenic
      phase of HSCT, fever occurred in 96 % of patients, and bacteremia was documented
      in 29 %. Coagulase-negative Staphylococcus was the most common isolated bacteria.
      Patients who developed bacteremia had a higher frequency of oral disorders
      compared with those without bacteremia, but it was not statistically significant.
      Oral mucositis affected 89.6 % of the patients, and patients with gingivitis or
      periodontal disorders had a high frequency of mucositis. CONCLUSIONS: The
      prevalence of oral pathologic conditions previous to HSCT procedures was very
      high in the studied population. A possible association was noted between previous
      gingivitis and the development of mucositis during the neutropenia of HSCT.

PMID- 23975230
TI  - Optimal control of nausea and vomiting with a three-drug antiemetic regimen with
      aprepitant in metastatic pancreatic cancer patients treated with first-line
      modified FOLFIRINOX.

PMID- 23975231
TI  - Daptomycin use in neutropenic patients with documented gram-positive infections.
AB  - PURPOSE: The goal of this study was to describe the outcomes associated with
      daptomycin treatment of documented gram-positive infections in patients with
      neutropenia. METHODS: All patients with neutropenia (<=500 cells/m(3)) and at
      least one documented gram-positive culture from 2006-2009 were identified from a
      retrospective, multicenter, and observational registry (Cubicin((r)) Outcome
      Registry and Experience (CORE((r)))). Investigators assessed patient outcome
      (cured, improved, failed, nonevaluable) at the end of daptomycin therapy. All
      patients were included in the safety analysis. RESULTS: The efficacy population
      had 186 patients; 159 (85 %) patients had either cure (n = 108, 58 %) or improved
      (n = 51, 27 %) as an outcome. Success rates (cure plus improved) by the lowest
      WBC during daptomycin were 98/116 (84 %) for <=100 cells/m(3) and 61/70 (87 %)
      for 101-499 cells/m(3), P = 0.6. Most patients had cancer; 135/186 (73 %) had
      hematological malignancy; 26/186 (14 %) had solid tumors, and 9 (5 %) had both.
      One hundred fifty-six (84 %) patients received other antibiotics before
      daptomycin treatment; 82 % vancomycin, of which 31 % failed vancomycin. The most
      common infections were bacteremia (78 %), skin and skin structure infections (8
      %), and urinary tract infections/pyelonephritis (6 %). The most common pathogens
      were vancomycin-resistant Enterococcus faecium (47 %), methicillin-resistant
      Staphylococcus aureus (20 %), and coagulase-negative staphylococci (19 %). The
      median (min, max) initial daptomycin dose was 6 mg/kg (3.6, 8.3). The median
      (min, max) daptomycin duration of therapy was 14 days (1, 86). Possibly related
      adverse events occurred in 12/209 patients (6 %), and 13 patients (6 %)
      discontinued daptomycin due to adverse event. CONCLUSIONS: The results suggest
      that daptomycin appeared useful and well tolerated in neutropenic patients, and
      the degree of neutropenia did not affect daptomycin success rates. Comparative
      clinical trials are needed to confirm these findings.

PMID- 23975232
TI  - The influence of alternative instruction on 6-min walk test distance.
AB  - BACKGROUND: The goal of the 6-min walk test (6MWT) is to enable patients to walk
      "as far as possible" as a measure of their functional ability. The impact of the
      specific walk instructions on patient 6MWT performance is unknown. METHODS:
      Patients with pulmonary arterial hypertension (PAH), idiopathic pulmonary
      fibrosis (IPF), and other forms of interstitial lung disease (ILD) were recruited
      to perform four identical 6MWTs with one differing instructional phrase. The
      standard instruction to walk "as far as possible" was substituted in random order
      with "as fast as possible," "at your normal pace," or "at a leisurely pace."
      RESULTS: Twenty-four patients (10 with PAH, eight with IPF, six with other ILD)
      were enrolled and completed all four 6MWTs. Patients attained the greatest
      distance with the fast instruction, exceeding the standard instruction distance
      by a mean of 52.7 m (P < .001). The mean difference between the fast and standard
      walks was 41.5 m in the PAH group, 66.5 m in the IPF group, and 53 m in the other
      ILD group. CONCLUSIONS: Patients do not walk as far as they are able with the
      standard American Thoracic Society instruction for 6MWT. Changing the wording
      from "far" to "fast" may facilitate a better effort and greater distance during
      the test. It is possible that this modified 6MWT instruction may result in
      improved accuracy and reproducibility, thereby enhancing its clinical and
      research trial usefulness.

PMID- 23975233
TI  - Graphene electronics for terahertz electron-beam radiation.
AB  - By virtue of their distinctive electronic properties (including linear energy
      dispersion, large velocity, and potentially ultra-high mobility even at room
      temperature), charge carriers in single-layer graphene are uniquely suited to
      radiation mechanisms that so far have been the primary domain of electron beams
      in vacuum-based systems. Here, we consider the use of sinusoidally corrugated
      graphene sheets for the generation of THz light based on a fundamentally new
      cyclotron-like radiation process, which does not require the application of any
      external magnetic field. Instead, periodic angular motion under bias is simply
      produced by the graphene mechanical corrugation, combined with its two
      dimensional nature which ensures that the carrier trajectories perfectly conform
      to the corrugation. Numerical simulations indicate that technologically
      significant output power levels can correspondingly be obtained at geometrically
      tunable THz frequencies. This mechanism (as well as similar electron-beam
      radiation processes such as the Smith-Purcell and Cherenkov effects in periodic
      nanostructures) may open the way for a new family of THz optoelectronic devices
      based on graphene, including solid-state 'free-electron' lasers potentially
      capable of room-temperature operation. 

PMID- 23975234
TI  - Vitamin D receptor (VDR) gene polymorphism influences the risk of osteoporosis in
      postmenopausal women of Northwest India.
AB  - SUMMARY: The influence of VDR gene for the risk of osteoporosis has remained
      inconclusive. VDR gene polymorphism in relation to BMD in postmenopausal women of
      Northwest India revealed a susceptibility haplotype AGT. Possession of this
      haplotype exacerbates the risk of osteoporosis by 2.8 times, which manifests in
      recessive mode of inheritance. PURPOSE: The purpose of this study is to
      understand the influence of coordinated effect of various single nucleotide
      polymorphisms (SNPs) within vitamin D receptor (VDR) gene for the risk of
      osteoporosis, which has remained undefined so far. METHODS: Four pertinent SNPs
      of VDR gene, i.e., rs2228570, rs1544410, rs17879735, and rs731236 were examined
      with polymerase chain reaction-restriction fragment length polymorphism in dual
      energy X-ray absorptiometry verified 188 osteoporotics, 115 osteopenics, and 147
      normal postmenopausal women of Northwest India. RESULTS: Minor allele 'T' of
      rs2228570 showed significant influence for the risk of osteoporosis (OR 1.60,
      95%CI 1.16-2.20, P=0.004) and also in dominant (OR 2.32, 95%CI 1.47-3.64,
      P=0.0006) and additive model (OR 2.41, 95%CI 1.49-3.87, P=0.0006) after
      Bonferroni correction. Minor allele (T) of rs2228570 showed an allele dose effect
      with BMD of L1-L4 (P=0.009) and FN (P=0.036). Disease association analysis
      exposed a susceptibility haplotype AGT which influences the risk of osteopenia
      (OR 2.04, 95%CI 1.03-4.08, P=0.036) and osteoporosis (OR 2.90, 95%CI 1.61-5.38,
      P=0.00005) after adjusting the effects of age, BMI and years since menopause.
      This haplotype is significantly associated with BMDs at lumbar spine (P=0.0001)
      and femoral neck (P=0.016). CONCLUSION: In-depth analysis of this haplotype with
      other methods of Wald statistics and Akaike information criterion confirmed that
      carriers of each unit of this haplotype AGT increases the risk of osteoporosis by
      a factor of 2.80+/-0.34 (beta+/-SE) which manifests (P=0.1 * 10-6) in its
      recessive mode of inheritance.

PMID- 23975235
TI  - Sri Lankan FRAX model and country-specific intervention thresholds.
AB  - SUMMARY: There is a wide variation in fracture probabilities estimated by Asian
      FRAX models, although the outputs of South Asian models are concordant.
      Clinicians can choose either fixed or age-specific intervention thresholds when
      making treatment decisions in postmenopausal women. Cost-effectiveness of such
      approach, however, needs to be addressed. PURPOSE: This study examined suitable
      fracture probability intervention thresholds (ITs) for Sri Lanka, based on the
      Sri Lankan FRAX model. METHODS: Fracture probabilities were estimated using all
      Asian FRAX models for a postmenopausal woman of BMI 25 kg/m2 and has no clinical
      risk factors apart from a fragility fracture, and they were compared. Age
      specific ITs were estimated based on the Sri Lankan FRAX model using the method
      followed by the National Osteoporosis Guideline Group in the UK. Using the age
      specific ITs as the reference standard, suitable fixed ITs were also estimated.
      RESULTS: Fracture probabilities estimated by different Asian FRAX models varied
      widely. Japanese and Taiwan models showed higher fracture probabilities while
      Chinese, Philippine, and Indonesian models gave lower fracture probabilities.
      Output of remaining FRAX models were generally similar. Age-specific ITs of major
      osteoporotic fracture probabilities (MOFP) based on the Sri Lankan FRAX model
      varied from 2.6 to 18% between 50 and 90 years. ITs of hip fracture probabilities
      (HFP) varied from 0.4 to 6.5% between 50 and 90 years. In finding fixed ITs, MOFP
      of 11% and HFP of 3.5% gave the lowest misclassification and highest agreement.
      CONCLUSION: Sri Lankan FRAX model behaves similar to other Asian FRAX models such
      as Indian, Singapore-Indian, Thai, and South Korean. Clinicians may use either
      the fixed or age-specific ITs in making therapeutic decisions in postmenopausal
      women. The economical aspects of such decisions, however, need to be considered.

PMID- 23975236
TI  - Population pharmacokinetics of peginterferon alfa-2b in pediatric patients with
      chronic hepatitis C.
AB  - PURPOSE: The aim of this study was to characterize the population
      pharmacokinetics of peginterferon (PEG-IFN) alfa-2b in pediatric patients with
      chronic hepatitis C and to identify covariates influencing PEG-IFN alfa-2b
      disposition. METHODS: Pharmacokinetic data from a multicenter open-label study of
      subcutaneously administered peginterferon alfa-2b (60 MUg/m(2)/wk) plus oral
      ribavirin (15 mg/kg/day) in patients with chronic hepatitis C aged 3-17 years old
      was used to develop a population pharmacokinetic nonlinear mixed-effects model.
      RESULTS: The final population pharmacokinetic analysis was conducted with the
      pooled data from 107 pediatric patients. A one-compartment model with first-order
      absorption, first-order elimination, exponential inter-individual variability on
      clearance, and a combination additive and proportional residual error model
      adequately described the PEG-IFN alfa-2b pharmacokinetic profile. Age (apparent
      clearance and apparent volume of distribution) and sex (apparent clearance) were
      significant covariates. The mean body surface area normalized apparent clearance
      of PEG-IFN alfa-2b was 0.56 L/h/m(2), and was similar when evaluated across the
      pediatric age groups. CONCLUSION: The final population model suggests age
      dependent increases in clearance and volume of distribution of PEG-IFN alfa-2b in
      pediatric patients with chronic hepatitis C. The apparent clearance normalized to
      body surface area was similar across pediatric age groups, supporting the use of
      body size-adjusted dosing in pediatric subjects.

PMID- 23975237
TI  - Practical recommendations for population PK studies with sampling time errors.
AB  - PURPOSE: Population pharmacokinetic (PK) data collected from routine clinical
      practice offers a rich source of valuable information. However, in observational
      population PK data, accurate time information for blood samples is often missing,
      resulting in measurement errors (ME) in the sampling time variable. The goal of
      this study was to investigate the effects on model parameters when a scheduled
      time is used instead of the actual blood sampling time, and to propose ME
      correction methods. METHODS: Simulation studies were conducted based on two major
      factors: the curvature in PK profiles and the size of ME. As ME correction
      methods, transform both sides (TBS) models were developed with application of Box
      Cox power transformation and Taylor expansion. The TBS models were compared to a
      conventional population PK model using simulations. RESULTS: The most important
      determinant of bias due to time ME was the degree of curvature (nonlinearity) in
      PK profiles; the smaller the curvature around sampling times, the smaller the
      associated bias. The second important determinant was the magnitude of ME; the
      larger the ME, the larger the bias. The proposed TBS models performed better than
      a conventional population PK modeling when curvature and ME were substantial.
      CONCLUSIONS: Time ME in sampling time can lead to bias on the parameter
      estimators. The following practical recommendations are provided: 1) when the
      curvature of PK profiles is small, conventional population PK modeling is robust
      to even large ME; and 2) when the curvature is moderate or large, the proposed
      methodology reduces bias in parameter estimates.

PMID- 23975239
TI  - Patient and public views on electronic health records and their uses in the
      United kingdom: cross-sectional survey.
AB  - BACKGROUND: The development and implementation of electronic health records
      (EHRs) remains an international challenge. Better understanding of patient and
      public attitudes and the factors that influence overall levels of support toward
      EHRs is needed to inform policy. OBJECTIVE: To explore patient and public
      attitudes toward integrated EHRs used simultaneously for health care provision,
      planning and policy, and health research. METHODS: Cross-sectional questionnaire
      survey administered to patients and members of the public who were recruited from
      a stratified cluster random sample of 8 outpatient clinics of a major teaching
      hospital and 8 general practices in London (United Kingdom). RESULTS: 5331
      patients and members of the public responded to the survey, with 2857 providing
      complete data for the analysis presented here. There were moderately high levels
      of support for integrated EHRs used simultaneously for health care provision,
      planning and policy, and health research (1785/2857, 62.47%), while 27.93%
      (798/2857) of participants reported being undecided about whether or not they
      would support EHR use. There were higher levels of support for specific uses of
      EHRs. Most participants were in favor of EHRs for personal health care provision
      (2563/2857, 89.71%), with 66.75% (1907/2857) stating that they would prefer their
      complete, rather than limited, medical history to be included. Of those
      "undecided" about integrated EHRs, 87.2% (696/798) were nevertheless in favor of
      sharing their full (373/798, 46.7%) or limited (323/798, 40.5%) records for
      health provision purposes. There were similar high levels of support for use of
      EHRs in health services policy and planning (2274/2857, 79.59%) and research
      (2325/2857, 81.38%), although 59.75% (1707/2857) and 67.10% (1917/2857) of
      respondents respectively would prefer their personal identifiers to be removed.
      Multivariable analysis showed levels of overall support for EHRs decreasing with
      age. Respondents self-identifying as Black British were more likely to report
      being undecided or unsupportive of national EHRs. Frequent health services users
      were more likely to report being supportive than undecided. CONCLUSIONS: Despite
      previous difficulties with National Health Service (NHS) technology projects,
      patients and the public generally support the development of integrated EHRs for
      health care provision, planning and policy, and health research. This support,
      however, varies between social groups and is not unqualified; relevant safeguards
      must be in place and patients should be guided in their decision-making process,
      including increased awareness about the benefits of EHRs for secondary uses.

PMID- 23975238
TI  - Circulating cells as predictors of secondary manifestations of cardiovascular
      disease: design of the CIRCULATING CELLS study.
AB  - Biomarkers for primary or secondary risk prediction of cardiovascular disease
      (CVD) are urgently needed to improve individual treatment and clinical trial
      design. The vast majority of biomarker discovery studies has concentrated on
      plasma/serum as an easily accessible source. Although numerous markers have been
      identified, their added predictive value on top of traditional risk factors has
      been limited, as the biological specimen does not specifically reflect expression
      profiles related with CVD progression and because the signal is often diluted by
      marker release from other organs. In contrast to serum markers, circulating cells
      serve as indicators of the actual disease state due to their active role in the
      pathogenesis of CVD and are responsible for the majority of secreted biomarkers.
      Therefore, the CIRCULATING CELLS study was initiated, focusing on the cellular
      effectors of atherosclerosis in the circulation. In total, 714 patients with
      coronary artery disease (CAD) symptoms were included. Blood cell fractions
      (monocytes, T-lymphocytes, platelets, granulocytes, PBMC) of all individual
      patients were isolated and stored for analysis. Concomitantly, extensive flow
      cytometric characterization of these populations was performed. From each
      patient, a detailed clinical profile together with extensive questionnaires about
      medical history and life style was obtained. Various high-throughput -omics
      approaches (protein, mRNA, miRNA) are currently being undertaken. Data will be
      integrated with advanced bioinformatics for discovery and validation of secondary
      risk markers for adverse events. Overall, the CIRCULATING CELLS study grants the
      interesting possibility that it will both identify novel biomarkers and provide
      useful insights into the pathophysiology of CAD in patients.

PMID- 23975240
TI  - Sustaining evidence-based prevention programs: correlates in a large-scale
      dissemination initiative.
AB  - Over the past four decades, significant strides have been made in the science of
      preventing youth problem behaviors. Subsequently, policymakers and funders have
      begun to insist on the use of evidence-based programs (EBPs) as a requirement for
      funding. However, unless practitioners are able to sustain these programs beyond
      initial seed funding, they are unlikely to achieve their ultimate goal of broad
      public health impact. Despite its obvious importance, sustainability has received
      relatively little attention in prevention science until recently. Moreover, there
      have been few opportunities to study the correlates of sustainability in large
      scale, multi-year initiatives involving multiple programs. The present study
      examined rates of sustainment of a wide range of proven-effective prevention and
      intervention programs; identified factors related to organizational support and
      readiness, program and implementer characteristics, and sustainability planning
      that distinguished sustained programs; and examined variability in these
      associations across classroom-based, community/mentoring, family-focused
      prevention, and family treatment program types within the context of a state-wide
      EBP dissemination initiative in Pennsylvania over 4 years. The majority of EBPs
      sustained functioning 2 years or more beyond their initial funding. In general,
      sustained programs reported greater community coalition functioning,
      communication to key stakeholders, knowledge of the program's logical model,
      communication with the trainer or program developer, and sustainability planning.
      In addition to these universal correlates, important program-specific correlates
      emerged as well. Implications for the technical assistance and support necessary
      to promote the sustainability of EBPs in nonresearch contexts are also discussed.

PMID- 23975241
TI  - Visual loss and perimetric sensitivity in eyes with retinitis pigmentosa.
AB  - PURPOSE: To investigate the various perimetric parameters that best predict
      reduction of best-corrected visual acuity (BCVA) to worse than 0.5 in the near
      future in eyes with retinitis pigmentosa (RP). METHODS: The most recent records
      obtained by Humphrey Field Analyzer (HFA) central 10-2 perimetry were studied for
      the right eyes of 123 patients (60 men and 63 women) with typical RP. The
      correlation between various parameters of perimetric sensitivity and BCVA was
      retrospectively studied. The receiver operating characteristic (ROC) curves were
      used to find the best parameter to discriminate eyes with BCVA >=0.5 from those
      with BCVA <0.5. RESULTS: Spearman rank correlation coefficients with logMAR BCVA
      were the highest for the foveal threshold (FT) and mean sensitivity of the test
      points within 1.4 degrees  of the fixation point (MS1.4). The ROC curve analysis
      revealed that the area under the curve was the largest for the MS1.4 among all
      the perimetric parameters for discriminating eyes with BCVA >=0.5 from those with
      BCVA <0.5. The cutoff value of 30 dB showed 100 % specificity and 57 %
      sensitivity. CONCLUSIONS: The risk of vision decreasing below 0.5 in the near
      future may be predicted when the mean sensitivity within 1.4 degrees  of the
      fixation point in the HFA 10-2 reaches 30 dB in eyes with RP.

PMID- 23975242
TI  - Lidamycin up-regulates the expression of thymidine phosphorylase and enhances the
      effects of capecitabine on the growth and pulmonary metastases of murine breast
      carcinoma.
AB  - PURPOSE: Capecitabine (CAP), a prodrug, needs to be converted to 5-fluorouracil
      by several key enzymes, including thymidine phosphorylase (TP). To improve the
      therapeutic index, potentiation of antitumor activity of CAP is required. In this
      study, we explored whether lidamycin (LDM), an enediyne anticancer antibiotic,
      can induce synergistic antitumor effects in combination with CAP in murine breast
      cancer in vitro and in vivo. METHODS: Using MTT, cell migration and invasion,
      siRNA knockdown, and Western blot assays, the in vitro synergistic effects of LDM
      plus CAP on 4T1(LUC) cells were evaluated, and the mechanism of this synergy was
      explored. For in vivo model of orthotopic implantation model of 4T1(LUC) cells,
      optical molecular imaging system was utilized to evaluate the growth of primary
      tumor and metastasis. To further understand the mechanism of action of the
      LDM/CAP combination, immunohistochemistry analysis was carried out to detect
      thymidine phosphorylase induction and ERK signaling. RESULTS: As determined by
      MTT and transwell assay, LDM enhanced the inhibitory effects of CAP on cancer
      cell proliferation, migration, and invasion. Western blot showed that this
      synergistic effect was attributed to the up-regulated expression of TP induced by
      LDM. Knocking down TP impaired the synergistic anti-proliferative effect of LDM
      and CAP. Furthermore, our data suggested that LDM-induced up-regulation of TP
      both in vitro and in vivo is associated with ERK activation, because the
      inhibition of ERK activity by ERK inhibitor U0126 abrogated LDM-induced TP up
      regulation. In animal models, LDM plus CAP potently inhibited primary tumor
      growth as well as lung metastasis compared with control or single-agent-treated
      group. CONCLUSIONS: LDM can potentiate the antitumor effects of CAP on breast
      cancer line. The synergistic effects suggest that the combination of LDM and CAP
      is an innovative antitumor strategy for breast cancer therapy.

PMID- 23975243
TI  - Phase II study of docetaxel and vinorelbine as adjuvant chemotherapy for resected
      non-small cell lung cancers.
AB  - PURPOSE: For patients with resected stage II-III non-small cell lung cancers
      (NSCLCs), adjuvant cisplatin-based chemotherapy improves survival over surgery
      alone. For cisplatin ineligible patients, there is no standard adjuvant option.
      We evaluated drug delivery and toxicity of docetaxel and vinorelbine in patients
      who could not receive cisplatin. METHODS: Patients with completely resected stage
      IB-III NSCLCs were treated with up to 4 cycles of docetaxel and vinorelbine at
      the recommended phase II dose. The primary endpoint was drug delivery compared to
      historical delivery of adjuvant cisplatin plus vinorelbine. Secondary endpoints
      were toxicity and feasibility. RESULTS: Twenty-five patients were enrolled.
      Overall, 13/25 (52 %, 95 % CI 34-70) completed 4 cycles, and 19/25 (76 %, 95 % CI
      60-87) completed >=3 cycles. Twenty of 25 patients (80 %) experienced a Grade 3
      or 4 adverse event. CONCLUSIONS: Delivery of this dose and schedule of docetaxel
      and vinorelbine was difficult with a dose delivery comparable to cisplatin plus
      vinorelbine, and cisplatin plus docetaxel, used in this setting.

PMID- 23975244
TI  - Clinical evaluation of targeted arterial perfusion of verapamil and
      chemotherapeutic drugs in interventional therapy of advanced lung cancer.
AB  - PURPOSE: To assess the clinical efficacy of targeted arterial perfusion of
      verapamil and chemotherapeutic agents in the interventional therapy of lung
      cancer. METHODS: Forty patients with advanced lung cancer underwent treatment
      with targeted arterial perfusion of verapamil and chemotherapeutic agents using
      Seldinger technique. Interventional therapy was performed once a month, and each
      subject received interventional treatment for 2 or more cycles. The therapeutic
      efficacy was evaluated 2 months post-treatment. RESULTS: Out of 40 patients with
      advanced lung cancer, 5 cases achieved complete remission (CR) and 29 cases
      achieved partial remission (PR), with a total effectiveness (CR + PR) rate of 85
      %. Besides, 32 cases achieved significantly alleviated clinical symptoms, and 29
      cases had decreased clinical tumor stage. All subjects had stable karnofsky
      performance status score and body weight. Among the 40 patients, 13 cases had
      leucopenia, 10 cases had gastrointestinal reactions, 3 cases presented with
      elevated alanine aminotransferase/aspartate aminotransferase ratio, and 3 cases
      had fever. However, all these side effects relieved quickly. No elevation of
      BUN/Cr ratio and allergic reactions was observed. No significant changes in
      cardiac function and electrocardiogram were noticed after the treatment.
      CONCLUSIONS: Targeted arterial perfusion of verapamil and chemotherapeutic drugs
      can improve the clinical symptoms of patients with advanced lung cancer and
      increase the efficacy of chemotherapeutic agents, thereby providing an
      opportunity for radiotherapy or surgical treatment for advanced lung cancer.

PMID- 23975245
TI  - Combined linkage and linkage disequilibrium QTL mapping in multiple families of
      maize (Zea mays L.) line crosses highlights complementarities between models
      based on parental haplotype and single locus polymorphism.
AB  - Advancements in genotyping are rapidly decreasing marker costs and increasing
      marker density. This opens new possibilities for mapping quantitative trait loci
      (QTL), in particular by combining linkage disequilibrium information and linkage
      analysis (LDLA). In this study, we compared different approaches to detect QTL
      for four traits of agronomical importance in two large multi-parental datasets of
      maize (Zea mays L.) of 895 and 928 testcross progenies composed of 7 and 21
      biparental families, respectively, and genotyped with 491 markers. We compared to
      traditional linkage-based methods two LDLA models relying on the dense genotyping
      of parental lines with 17,728 SNP: one based on a clustering approach of parental
      line segments into ancestral alleles and one based on single marker information.
      The two LDLA models generally identified more QTL (60 and 52 QTL in total) than
      classical linkage models (49 and 44 QTL in total). However, they performed
      inconsistently over datasets and traits suggesting that a compromise must be
      found between the reduction of allele number for increasing statistical power and
      the adequacy of the model to potentially complex allelic variation. For some QTL,
      the model exclusively based on linkage analysis, which assumed that each parental
      line carried a different QTL allele, was able to capture remaining variation not
      explained by LDLA models. These complementarities between models clearly suggest
      that the different QTL mapping approaches must be considered to capture the
      different levels of allelic variation at QTL involved in complex traits. 

PMID- 23975246
TI  - Gene discovery and functional marker development for fragrance in sorghum
      (Sorghum bicolor (L.) Moench).
AB  - KEY MESSAGE: Sequence analysis and genetic mapping revealed that a 1,444 bp
      deletion causes a premature stop codon in SbBADH2 of sorghum IS19912. The non
      function of SbBADH2 is responsible for fragrance in sorghum IS19912. 2-acetyl-1
      pyrroline (2AP) is a potent volatile compound causing fragrance in several plants
      and foods. Seeds of some varieties of rice, sorghum and soybean possess
      fragrance. The genes responsible for fragrance in rice and soybean are orthologs
      that correspond to betaine aldehyde dehydrogenase 2 (BADH2). Genotypes harboring
      fragrance in rice and soybean contain a premature stop codon in BADH2 which
      impairs the synthesis of full length functional BADH2 protein leading to the
      accumulation of 2AP. In this study, we reported an association between the BADH2
      gene and fragrance in sorghum. An F2 population of 187 plants developed from a
      cross between KU630 (non-fragrant) and IS19912 (fragrant) was used. Leaves of F2
      and F3 progenies were evaluated for fragrance by organoleptic test, while seeds
      of F2 plants were analyzed for 2AP. The tests consistently showed that the
      fragrance is controlled by a single recessive gene. Gene expression analysis of
      SbBADH1 and SbBADH2 in leaves of KU630 and IS19912 at various stages revealed
      that SbBADH1 and SbBADH2 were expressed in both accessions. Sequence comparison
      between KU630 and IS19912 revealed a continuous 1,444 bp deletion encompassing
      exon 12 to 15 of SbBADH2 in IS19912 which introduces a frameshift mutation and
      thus causes a premature stop codon. An indel marker was developed to detect
      polymorphism in SbBADH2. Bulk segregant and QTL analyses confirmed the
      association between SbBADH2 and fragrance.

PMID- 23975248
TI  - Development of clinical neuropathology in china during the past half century: a
      publication survey.

PMID- 23975249
TI  - Does research participation make a difference in residency training?
AB  - BACKGROUND: The American Board of Orthopaedic Surgery requirements state that an
      orthopaedic residency must offer at least 5 years of clinical education and some
      exposure to research. To expose residents to basic research, some programs,
      including ours, have a research track that allows for 1 year of basic science
      research. The degree to which research productivity during residency-which may be
      something that can perhaps be influenced by interventions like research tracks
      during residency-affects residency graduates' future research contributions is
      unknown. QUESTIONS/PURPOSES: Our research goals were to determine whether (1)
      residents who published in a peer-reviewed journal during residency were more
      likely to publish in their careers after graduation; (2) residents who
      participated in an elective research year were more likely to publish at least
      one paper in a peer-reviewed journal during residency; and (3) residents who
      participated in the research year were more likely to choose academic careers.
      METHODS: Using questionnaires, online PubMed searches, and office contact, the
      career paths (academic versus private practice) and publications in peer-reviewed
      journals of all 122 Case Western Reserve University orthopaedics residents who
      completed training from 1987 to 2006 were analyzed. RESULTS: Seventy-five percent
      of residents who published peer-reviewed research during residency continued with
      peer-reviewed publications in their careers versus 55% of residents who did not
      publish during residency (p = 0.02). No difference in career paths was observed
      between the Case Western Reserve University research and traditional track
      trained surgeons. During residency, however, research track-trained surgeons were
      more likely to publish in peer-reviewed journals (71% versus 41% of traditional
      track-trained surgeons, p < 0.01). CONCLUSIONS: Residents who publish in a peer
      reviewed journal during residency are more likely to continue publishing in their
      future careers as orthopaedic surgeons. Future studies are needed to elucidate
      the causative factors in the association between publishing in a peer-reviewed
      journal during training and further contributions later in an orthopaedic
      surgeon's career.

PMID- 23975250
TI  - Randomized trial of hemiarthroplasty versus internal fixation for femoral neck
      fractures: no differences at 6 years.
AB  - BACKGROUND: Hemiarthroplasty has been shown superior to internal fixation for
      displaced femoral neck fractures (FNF) in the first 2 years. However, there are
      unanswered questions about the performance of hemiarthroplasty over the longer
      term compared with internal fixation. QUESTIONS/PURPOSES: We sought to compare
      hemiarthroplasty with internal fixation in terms of (1) outcomes scores for pain,
      hip function, and quality of life at a minimum of 5 years after surgery in a
      randomized trial. A secondary purpose was to compare (2) patient survival and (3)
      frequency of reoperation in the two groups. METHODS: A total of 222 consecutive
      patients older than 60 years, including those cognitively impaired, with FNF were
      randomized to either internal fixation with two parallel screws or bipolar
      hemiarthroplasty. At a minimum followup of 4.9 years (mean, 5.9 years; range, 4.9
      7.2 years), 68 of the 70 surviving patients were examined by a study nurse and
      study physiotherapist blinded to initial treatment. Questionnaires on hip
      function (Harris hip score), quality of life (Eq5D), and activity of daily living
      function (Barthel ADL) were administered. The Barthel ADL index score was split
      into good function (score 95 or 100) and reduced function (score below 95).
      RESULTS: The mean survival of the groups was similar with 66.4% (73 of 110) of
      the patients undergoing hemiarthroplasty and 70.5% (79 of 112) of the patients
      undergoing internal fixation having died since surgery (p = 0.51). Only 12 of 31
      living patients in the internal fixation group had retained their native hips at
      a mean of 6 years. Between 2 and 6 years, there were two new major reoperations
      (both in the internal fixation group, for avascular necrosis and deep wound
      infection). The mean Harris hip score was 66 (SD 19) and 67 (SD 20) in the
      internal fixation and hemiarthroplasty groups, respectively (p = 0.96). The mean
      Eq5D index was 0.50 (SD 0.40) in the internal fixation group and 0.34 (SD 0.36)
      in the hemiarthroplasty group (p = 0.10). Function in terms of ADLs was
      comparable between the groups; of the patients in the internal fixation group,
      42% reported good function on the Barthel ADL index, and the corresponding number
      in the hemiarthroplasty group was 51% (p = 0.44). CONCLUSIONS: Hemiarthroplasty
      has predictable and good long-term results after FNF and is the treatment of
      choice compared with internal fixation. Further studies will evaluate if total
      hip arthroplasty has advantages over hemiarthroplasty in patients with fracture
      with long life expectancy.

PMID- 23975251
TI  - Loss of cement-bone interlock in retrieved tibial components from total knee
      arthroplasties.
AB  - BACKGROUND: Aseptic loosening continues to be a short- and long-term complication
      for patients with cemented TKAs. Most studies to this point have evaluated tibial
      component fixation via radiographic changes at the implant-bone interface and
      quantification of component migration; direct assessment of morphologic features
      of the interface from functioning TKAs may provide new information regarding how
      TKAs function and are fixed to bone. QUESTIONS/PURPOSES: In a postmortem
      retrieval study, we asked: (1) What are the morphologic features at the cement
      trabecular bone interface in retrieved tibial components? (2) Do constructs with
      greater time in service have less cement-trabecular bone interlock? (3) Do
      constructs with more estimated initial interlock sustain more interlock with in
      vivo service? METHODS: Fourteen postmortem retrieved tibial components with time
      in service from 0 to 20 years were sectioned and imaged at high resolution, and
      the current contact fraction, estimated initial interdigitation depth, current
      interdigitation depth, and loss of interdigitation depth were quantified at the
      cement-bone interface. Estimated initial interdigitation depth was calculated
      from the initial mold shape of the cement mantle that forms around the individual
      trabeculae at the time of surgery. Loss of interdigitation depth was the
      difference between the initial and current interdigitation depth. RESULTS: There
      was resorption of trabeculae that initially interlocked with the cement in the
      postmortem retrievals as evidenced by the differences between current
      interdigitation and the estimated original interdigitation. The current contact
      fraction (r(2) = 0.54; p = 0.0027) and current interdigitation depth (r(2) =
      0.33; p = 0.033) were less for constructs with longer time in service. The
      current contact fraction for implants with 10 or more years in service (6.2%; 95%
      CI, 4.7%-7.7%) was much less than implants with less than 10 years in service
      (22.9%; 95% CI, 8.9%-37%). Similarly, the current interdigitation depth for
      implants with 10 or more years in service (0.4 mm; 95% CI, 0.27-0.53 mm) was much
      less than implants with less than 10 years in service (1.13 mm; 95% CI, 0.48-1.78
      mm). The loss of interdigitation depth had a strong positive relationship with
      time in service (r(2) = 0.74; p < 0.001). Using a two-parameter regression model,
      constructs with more initial interdigitation depth had greater current
      interdigitation depth (p = 0.011), but constructs with more time in service also
      had less current interdigitation depth (p = 0.008). CONCLUSIONS: The cement
      trabecular bone interlock obtained initially appears to diminish with time with
      in vivo service by resorption of the trabeculae in the cement interlock region.
      CLINICAL RELEVANCE: Our study supports the surgical concept of obtaining
      sufficient initial cement interlock (approximately 3 mm), with the acknowledgment
      that there will be loss of interlock with time with in vivo service.

PMID- 23975253
TI  - CORR Insights (r): The Oxford unicompartmental knee fails at a high rate in a
      high-volume knee practice.

PMID- 23975252
TI  - Infection after surgical resection for pelvic bone tumors: an analysis of 270
      patients from one institution.
AB  - BACKGROUND: Surgical treatment of pelvic tumors with or without acetabular
      involvement is challenging. Primary goals of surgery include local control and
      maintenance of good quality of life, but the procedures are marked by significant
      perioperative morbidity and complications. QUESTIONS/PURPOSES: We wished to (1)
      evaluate the frequency of infection after limb salvage surgical resection for
      bone tumors in the pelvis; (2) determine whether infection after these resections
      is associated with particular risk factors, including pelvic reconstruction,
      radiotherapy or chemotherapy, type of resection, and age; and (3) analyze
      treatment of these infections, particularly with respect to the need of
      additional surgery or hemipelvectomy. METHODS: From 1975 to 2010, 270 patients
      with pelvic bone tumors (149 with chondrosarcoma, 40 with Ewing's sarcoma, 27
      with osteosarcoma, 18 with other primary malignant tumors, 11 with metastatic
      tumors, and 25 with primary benign tumors) were treated by surgical resection.
      Minimum followup was 1.1 years (mean, 8 years; range, 1-33 years). The resection
      involved the periacetabular area in 166 patients. In 137 patients reconstruction
      was performed; in 133 there was no reconstruction. Chart review ascertained the
      frequency of deep infections, how they were treated, and the frequency of
      resection arthroplasty or hemipelvectomies that occurred thereafter. RESULTS: A
      total of 55 patients (20%) had a deep infection develop at a mean followup of 8
      months. There were 20 infections in 133 patients without reconstruction (15%) and
      35 infections in 137 patients with reconstruction (26 %). Survivorship rates of
      the index procedures using infection as the end point were 87%, 83%, and 80% at 1
      month, 1 year, and 5 years, respectively. Infection was more common in patients
      who underwent pelvic reconstruction after resection (univariate analysis, p =
      0.0326; multivariate analysis, p = 0.0418; odds ratio, 1.7718; 95% CI, 1.0243
      3.0650); no other risk factors we evaluated were associated with an increased
      likelihood of infection. Despite surgical debridements and antibiotics, 16
      patients (46%) had the implant removed and five (9%) underwent external
      hemipelvectomy (four owing to infection and one as a result of persistent
      infection and local recurrence). CONCLUSIONS: Infection is a common complication
      of pelvic resection for bone tumors. Reconstruction after resection is associated
      with an increased risk of infection compared with resection alone, without
      significant difference in percentage between allograft and metallic prosthesis.
      When infection occurs, it requires removal of the implant in nearly half of the
      patients who have this complication develop, and external hemipelvectomy
      sometimes is needed to eradicate the infection.

PMID- 23975254
TI  - A case of mycosis fungoides with large cell transformation associated with
      infliximab treatment.

PMID- 23975255
TI  - CD105 is a more appropriate marker for evaluating angiogenesis in urothelial
      cancer of the upper urinary tract than CD31 or CD34.
AB  - Angiogenesis plays an important role in cancer progression in many types of
      cancer. Evaluation of angiogenesis is often performed, but the optimal
      methodology for human cancer has not been agreed upon. As adequate evaluation of
      angiogenesis in cancer tissues might be important for prediction of prognosis and
      treatment decisions, we evaluated angiogenesis semiquantitatively by assessing
      microvessel density (MVD) in urothelial cancer of the upper urinary tract (UC
      UUT). We compared the performance of three endothelial cell markers (CD31, CD34,
      and CD105) on formalin-fixed tissues from 122 patients diagnosed with UC-UUT
      without metastasis. Vascular endothelial growth factor (VEGF)-A expression was
      also evaluated immunohistochemically. Correlations between MVD with each marker
      and pT stage, grade, survival, and VEGF-A expression were investigated. Mean
      (standard deviation) MVD as estimated by immunohistochemical staining with anti
      CD31, anti-CD34, and anti-CD105 were 47.1 (17.9)/high-power field (HPF), 70.9
      (19.5)/HPF, and 31.2 (16.7)/HPF, respectively. Although all MVDs were
      significantly associated with pT stage and grade, CD105-MVD showed the strongest
      association. Similarly, CD105-MVD showed the strongest correlation with VEGF-A
      expression (r = 0.530, p < 0.001). Although all MVDs were associated with
      metastasis-free survival and cause-specific survival on univariate analysis, only
      CD105-MVD was retained as an independent predictor in multivariate analysis
      including pT stage and grade. CD105-MVD may be the preferred marker for
      semiquantitative assessment of angiogenesis in patients with UC-UUT.

PMID- 23975256
TI  - A plea to reduce or replace fetal bovine serum in cell culture media.

PMID- 23975258
TI  - Children's knowledge of ellipsis constructions in Mandarin Chinese.
AB  - This study investigated 4-year-old children's knowledge of the structural
      constraints on ellipsis constructions in Mandarin Chinese, focusing on the
      structural difference between verb phrase (VP) ellipsis and null object
      constructions. In Mandarin Chinese, if the antecedent clause of a VP-ellipsis
      structure contains an adverbial modifier, this adverbial modifier must be
      recovered at the elided site in the second clause. However, if the antecedent
      clause of a null object construction contains an adverbial modifier, the
      reconstruction of this adverbial modifier at the elided site is not necessary.
      Two experiments were conducted to examine whether young Mandarin-speaking
      children are sensitive to this structural difference between the two ellipsis
      constructions. The results show that children exhibited adult-like performance in
      both experiments. This is evidence that young Mandarin-speaking children have
      knowledge of the structural difference between VP-ellipsis and null object
      constructions with regard to adverbial recovery. We interpreted the findings in
      conjunction with previous research as evidence that children's knowledge of the
      structural constraints on ellipsis constructions is innately specified. 

PMID- 23975257
TI  - The effects of age on second language grammar and speech production.
AB  - The current study examined the age of learning effect on second language (L2)
      acquisition. The research goals of the study were twofold: to test whether there
      is an independent age effect controlling for other potentially confounding
      variables, and to clarify the age effect across L2 grammar and speech production
      domains. The study included 118 Mandarin-speaking immigrants and 24 native
      English speakers. Grammar knowledge was assessed by a grammaticality judgment
      task, and speech production was measured by native English speaking raters'
      ratings of participants' foreign accents. Results from the study revealed that
      the age of learning effect was robust for both L2 domains even after controlling
      for the influences of other variables, such as length of residence and years of
      education in the United States. However, the age of learning variable had a
      stronger impact on speech production than on grammar. The current results support
      the framework of multiple critical/sensitive periods (Long in Int Rev Appl
      Linguist 43(4):287-317, 2005; Newport et al. in Language, brain and cognitive
      development: Essays in honor of Jacques Mehler. MIT Press, Cambridge, MA, 2001;
      Werker and Tees in Dev Psychobiol 46(3):233-251, 2005). 

PMID- 23975259
TI  - Plasmonic ELISA for the detection of analytes at ultralow concentrations with the
      naked eye.
AB  - This protocol describes a signal-generation mechanism for the naked-eye detection
      of analytes at low concentrations with ELISA. The key step is to generate
      solutions of desired tonality by growing gold nanoparticles with a particular
      state of aggregation. This is accomplished by linking the growth of gold
      nanoparticles with the biocatalytic cycle of the enzyme label. The protocol
      adapts a conventional ELISA procedure with catalase-labeled antibodies. The
      enzyme consumes hydrogen peroxide, and then gold (III) ions are added to generate
      gold nanoparticles. The concentration of hydrogen peroxide dictates the state of
      aggregation of gold nanoparticles. This allows for the naked-eye detection of
      analytes by observing the generation of blue- or red-colored gold nanoparticle
      solutions. When coupled with conventional ELISA, this signal-generation procedure
      allows for the naked-eye detection of analytes within 1 h. 

PMID- 23975260
TI  - Count-based differential expression analysis of RNA sequencing data using R and
      Bioconductor.
AB  - RNA sequencing (RNA-seq) has been rapidly adopted for the profiling of
      transcriptomes in many areas of biology, including studies into gene regulation,
      development and disease. Of particular interest is the discovery of
      differentially expressed genes across different conditions (e.g., tissues,
      perturbations) while optionally adjusting for other systematic factors that
      affect the data-collection process. There are a number of subtle yet crucial
      aspects of these analyses, such as read counting, appropriate treatment of
      biological variability, quality control checks and appropriate setup of
      statistical modeling. Several variations have been presented in the literature,
      and there is a need for guidance on current best practices. This protocol
      presents a state-of-the-art computational and statistical RNA-seq differential
      expression analysis workflow largely based on the free open-source R language and
      Bioconductor software and, in particular, on two widely used tools, DESeq and
      edgeR. Hands-on time for typical small experiments (e.g., 4-10 samples) can be <1
      h, with computation time <1 d using a standard desktop PC. 

PMID- 23975261
TI  - Exome sequencing in a family with intellectual disability, early onset
      spasticity, and cerebellar atrophy detects a novel mutation in EXOSC3.
AB  - Whole exome sequencing in two-generational kindred from Bangladesh with early
      onset spasticity, mild intellectual disability, distal amyotrophy, and cerebellar
      atrophy transmitted as an autosomal recessive trait identified the following two
      missense mutations in the EXOSC3 gene: a novel p.V80F mutation and a known
      p.D132A change previously associated with mild variants of pontocerebellar
      hypoplasia type 1. This study confirms the involvement of RNA processing proteins
      in disorders with motor neuron and cerebellar degeneration overlapping with
      spinocerebellar ataxia 36 and rare forms of hereditary spastic paraplegia with
      cerebellar features. 

PMID- 23975262
TI  - Investigating well-being, work limitations and preferences for self-management
      education and peer support among younger people with hip and knee osteoarthritis:
      protocol for a cross-sectional study.
AB  - INTRODUCTION: Osteoarthritis (OA) has traditionally been considered a condition
      of older age. However, younger people are also affected by hip and knee OA, often
      as a result of sporting and work-related injuries. As OA studies have generally
      focused on older individuals, little is known about the experience of younger
      adults with hip or knee OA who can face a distinct set of pressures including
      work responsibilities and parenting roles. This study aims to investigate well
      being and work participation among younger people with hip or knee OA, as well as
      preferences for OA education and support. METHODS AND ANALYSIS: 200 people aged
      20-55 years with a diagnosis of hip and/or knee OA will be recruited for this
      cross-sectional study. Participants will be recruited from three major public
      hospitals in the state of Victoria, Australia following screening of orthopaedic
      outpatient clinic lists and referrals, and through community-based
      advertisements. A study questionnaire will be mailed to all participants and
      written informed consent obtained. Validated measures of Health-Related Quality
      of Life (HRQoL), health status, psychological distress and work limitations will
      be used. Information on health services use will be collected, in addition to
      information on the perceived utility and accessibility of a range of existing and
      proposed education and peer support models. HRQoL data will be compared with
      Australian population norms using independent t tests, and associations between
      HRQoL, health status, psychological distress, work limitations and demographic
      factors will be evaluated using univariate and multivariate analyses. Data on the
      perceived utility and accessibility of education and peer support models will be
      analysed descriptively. ETHICS AND DISSEMINATION: Ethics approval for the study
      has been obtained. The study findings will be submitted to peer-reviewed journals
      and arthritis consumer organisations for broader dissemination, and presented at
      national and international scientific meetings.

PMID- 23975263
TI  - A comparison of Australian rural and metropolitan cardiovascular risk and
      mortality: the Greater Green Triangle and North West Adelaide population surveys.
AB  - OBJECTIVES: Cardiovascular (CVD) mortality disparities between rural/regional and
      urban-dwelling residents of Australia are persistent. Unavailability of
      biomedical CVD risk factor data has, until now, limited efforts to understand the
      causes of the disparity. This study aimed to further investigate such
      disparities. DESIGN: Comparison of (1) CVD risk measures between a regional
      (Greater Green Triangle Risk Factor Study (GGT RFS, cross-sectional study, 2004
      2006) and an urban population (North West Adelaide Health Study (NWAHS,
      longitudinal cohort study, 2004-2006); (2) Australian Bureau of Statistics (ABS)
      CVD mortality rates between these and other Australian regions; and (3) ABS CVD
      mortality rates by an area-level indicator of socioeconomic status, the Index of
      Relative Socioeconomic Disadvantage (IRSD). SETTING: Greater Green Triangle (GGT,
      Limestone Coast, Wimmera and Corangamite Shires) of South-Western Victoria and
      North-West Adelaide (NWA). PARTICIPANTS: 1563 GGT RFS and 3036 NWAHS stage 2
      participants (aged 25-74) provided some information (self-administered
      questionnaire +/- anthropometric and biomedical measurements). PRIMARY AND
      SECONDARY OUTCOME MEASURES: Age-group specific measures of absolute CVD risk, ABS
      CVD mortality rates by study group and Australian Standard Geographical
      Classification (ASGC) region. RESULTS: Few significant differences in CVD risk
      between the study regions, with mean absolute CVD risk ranging from approximately
      1% in the age group 35-39 years to 14% in the age group 70-74 years. [corrected].
      Similar mean 2003-2007 (crude) mortality rates in GGT (98, 95% CI 87 to 111), NWA
      (103, 95% CI 96 to 110) and regional Australia (92, 95% CI 91 to 94). NWA
      mortality rates exceeded that of other city areas (70, 95% CI 69 to 71). Lower
      measures of socioeconomic status were associated with worse CVD outcomes
      regardless of geographic location. CONCLUSIONS: Metropolitan areas do not always
      have better CVD risk factor profiles and outcomes than rural/regional areas.
      Needs assessments are required for different settings to elucidate relative
      contributions of the multiple determinants of risk and appropriate cardiac
      healthcare strategies to improve outcomes.

PMID- 23975264
TI  - Development and application of a novel metric to assess effectiveness of
      biomedical data.
AB  - OBJECTIVE: Design a metric to assess the comparative effectiveness of biomedical
      data elements within a study that incorporates their statistical relatedness to a
      given outcome variable as well as a measurement of the quality of their
      underlying data. MATERIALS AND METHODS: The cohort consisted of 874 patients with
      adenocarcinoma of the lung, each with 47 clinical data elements. The p value for
      each element was calculated using the Cox proportional hazard univariable
      regression model with overall survival as the endpoint. An attribute or A-score
      was calculated by quantification of an element's four quality attributes;
      Completeness, Comprehensiveness, Consistency and Overall-cost. An effectiveness
      or E-score was obtained by calculating the conditional probabilities of the p
      value and A-score within the given data set with their product equaling the
      effectiveness score (E-score). RESULTS: The E-score metric provided information
      about the utility of an element beyond an outcome-related p value ranking. E
      scores for elements age-at-diagnosis, gender and tobacco-use showed utility above
      what their respective p values alone would indicate due to their relative ease of
      acquisition, that is, higher A-scores. Conversely, elements surgery-site,
      histologic-type and pathological-TNM stage were down-ranked in comparison to
      their p values based on lower A-scores caused by significantly higher acquisition
      costs. CONCLUSIONS: A novel metric termed E-score was developed which
      incorporates standard statistics with data quality metrics and was tested on
      elements from a large lung cohort. Results show that an element's underlying data
      quality is an important consideration in addition to p value correlation to
      outcome when determining the element's clinical or research utility in a study.

PMID- 23975265
TI  - Incorporation of assessments of risk of bias of primary studies in systematic
      reviews of randomised trials: a cross-sectional study.
AB  - OBJECTIVE: We examined how assessments of risk of bias of primary studies are
      carried out and incorporated into the statistical analysis and overall findings
      of a systematic review. DESIGN: A cross-sectional review. SAMPLE: We assessed 200
      systematic reviews of randomised trials published between January and March 2012;
      Cochrane (n=100), non-Cochrane (Database of Reviews of Effects) (n=100). MAIN
      OUTCOMES: Our primary outcome was a descriptive analysis of how assessments of
      risk of bias are carried out, the methods used, and the extent to which such
      assessments were incorporated into the statistical analysis and overall review
      findings. RESULTS: While Cochrane reviews routinely reported the method of risk
      of bias assessment and presented their results either in text or table format,
      20% of non-Cochrane reviews failed to report the method used and 39% did not
      present the assessment results. Where it was possible to evaluate the individual
      results of the risk of bias assessment (n=154), 75% (n=116/154) of reviews had
      >=1 trial at high risk of bias; the median proportion of trials per review at
      high risk of bias was 50% (IQR 31% to 89%). Despite this, only 56% (n=65/116)
      incorporated the risk of bias assessment into the interpretation of the results
      in the abstract and 41% (n=47/116) (49%; n=40/81 Cochrane and 20%; n=7/35 non
      Cochrane) incorporated the risk of bias assessment into the interpretation of the
      conclusions. Of the 83% (n=166/200) systematic reviews which included a meta
      analysis, only 11% (n=19/166) incorporated the risk of bias assessment into the
      statistical analysis. CONCLUSIONS: Cochrane reviews were more likely than non
      Cochrane reviews to report how risk of bias assessments of primary studies were
      carried out; however, both frequently failed to take such assessments into
      account in the statistical analysis and conclusions of the systematic review.

PMID- 23975268
TI  - Editorial: addressing controversies in pediatric oncology.

PMID- 23975267
TI  - Controversies in the role of radiotherapy in the treatment of pediatric Hodgkin
      lymphoma.
AB  - Hodgkin lymphoma in children is a highly curable malignancy with current
      approaches utilizing combined modality therapy and a risk-adapted approach. The
      combination of anthracyclines, bleomycin, and radiotherapy, as well as other
      alkylating agents, are significant risk factors for secondary malignancies and
      cardiopulmonary toxicity. Therefore, current strategies aim to optimize cure
      rates while minimizing late effects. The role of radiotherapy has been examined
      in recent pediatric trials, with varying results. However, they provide evidence,
      as a whole, for the omission of radiotherapy for a subgroup of patients, without
      compromising outcomes. 

PMID- 23975269
TI  - Reconsidering the politics of public health.

PMID- 23975266
TI  - Alterations of DNA methylome in human bladder cancer.
AB  - Bladder cancer is the fourth most common cancer in men in the United States, and
      its recurrence rate is highest among all malignancies. The unmet need for
      improved strategies for early detection, treatment, and monitoring of the
      progression of this disease continues to translate into high mortality and
      morbidity. The quest for advanced diagnostic, therapeutic, and prognostic
      approaches for bladder cancer is a high priority, which can be achieved by
      understanding the molecular mechanisms of the initiation and progression of this
      malignancy. Aberrant DNA methylation in single or multiple cancer-related
      genes/loci has been found in human bladder tumors and cancer cell lines, and
      urine sediments, and correlated with many clinicopathological features of this
      disease, including tumor relapse, muscle-invasiveness, and survival. The present
      review summarizes the published research on aberrant DNA methylation in
      connection with human bladder cancer. Representative studies are highlighted to
      set forth the current state of knowledge, gaps in the knowledgebase, and future
      directions in this prime epigenetic field of research. Identifying the
      potentially reversible and 'drugable' aberrant DNA methylation events that
      initiate and promote bladder cancer development can highlight biological markers
      for early diagnosis, effective therapy and accurate prognosis of this malignancy.

PMID- 23975270
TI  - The association of insomnia with gastroesophageal reflux symptoms in biopsy
      proven nonalcoholic fatty liver disease.
AB  - BACKGROUND: It is suggested that nonalcoholic fatty liver disease (NAFLD),
      including nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis
      (NASH), can be associated with insomnia and gastro-esophageal reflux disease
      (GERD). The relationship between GERD and insomnia in subjects with biopsy-proven
      NAFLD was investigated. METHODS: This study enrolled 123 patients with biopsy
      proven NAFLD. Insomnia was assessed by the Athens Insomnia Scale (AIS), a self
      assessment psychometric instrument designed to quantify sleep difficulty based on
      ICD-10 criteria; AIS scores >= 6 were considered positive for insomnia. GERD
      symptoms were evaluated using a frequency scale for the symptoms of GERD (FSSG);
      FSSG scores >= 8 were considered positive. Logistic regression models were used
      to evaluate the association of insomnia with GERD, after adjusting for potential
      confounders. Thirteen patients with GERD were treated with the proton pump
      inhibitor rabeprazole (RPZ; 10 mg/day), for 12 weeks. RESULTS: Of the 123
      patients, 76 (62%) were female and 87 (71%) were obese, with 34 (28%) having AIS
      scores >= 6 and 31 (25%) having FSSG scores >= 8. Liver biopsy revealed that 40
      patients (33%) had NAFL and 83 (67%) had NASH. FSSG and AIS scores were similar
      in the two groups. HOMA-IR, FSSG scores and gammaGT (GGT) concentrations were
      significantly higher in insomniacs than in non-insomniacs. Logistic regression
      analysis demonstrated that FSSG score and GGT concentration were independently
      associated with insomnia. RPZ treatment resulted in significantly reductions in
      both AIS and FSSG scores. CONCLUSIONS: Nearly 30% of patients with biopsy-proven
      NAFLD had insomnia, which was related to GGT and GERD and could be relieved by
      RPZ treatment.

PMID- 23975271
TI  - Experimental versus predicted affinities for ligand binding to estrogen receptor:
      iterative selection and rescoring of docked poses systematically improves the
      correlation.
AB  - The computational determination of binding modes for a ligand into a protein
      receptor is much more successful than the prediction of relative binding
      affinities (RBAs) for a set of ligands. Here we consider the binding of a set of
      26 synthetic A-CD ligands into the estrogen receptor ERalpha. We show that the
      MOE default scoring function (London dG) used to rank the docked poses leads to a
      negligible correlation with experimental RBAs. However, switching to an energy
      based scoring function, using a multiple linear regression to fit experimental
      RBAs, selecting top-ranked poses and then iteratively repeating this process
      leads to exponential convergence in 4-7 iterations and a very strong correlation.
      The method is robust, as shown by various validation tests. This approach may be
      of general use in improving the quality of predicted binding affinities. 

PMID- 23975272
TI  - Systematic mining of analog series with related core structures in multi-target
      activity space.
AB  - We have aimed to systematically extract analog series with related core
      structures from multi-target activity space to explore target promiscuity of
      closely related analogous. Therefore, a previously introduced SAR matrix
      structure was adapted and further extended for large-scale data mining. These
      matrices organize analog series with related yet distinct core structures in a
      consistent manner. High-confidence compound activity data yielded more than 2,300
      non-redundant matrices capturing 5,821 analog series that included 4,288 series
      with multi-target and 735 series with multi-family activities. Many matrices
      captured more than three analog series with activity against more than five
      targets. The matrices revealed a variety of promiscuity patterns. Compound series
      matrices also contain virtual compounds, which provide suggestions for compound
      design focusing on desired activity profiles. 

PMID- 23975273
TI  - The Authors' reply.

PMID- 23975274
TI  - Carotid plaque typisation: a novel risk marker?

PMID- 23975275
TI  - Prolonged hemodynamic response during incidental facial emotion processing in
      inter-episode bipolar I disorder.
AB  - This fMRI study examined whether hemodynamic responses to affectively-salient
      stimuli were abnormally prolonged in remitted bipolar disorder, possibly
      representing a novel illness biomarker. A group of 18 DSM-IV bipolar I-diagnosed
      adults in remission and a demographically-matched control group performed an
      event-related fMRI gender-discrimination task in which face stimuli had task
      irrelevant neutral, happy or angry expressions designed to elicit incidental
      emotional processing. Participants' brain activation was modeled using a "fully
      informed" SPM5 basis set. Mixed-model ANOVA tested for diagnostic group
      differences in BOLD response amplitude and shape within brain regions-of-interest
      selected from ALE meta-analysis of previous comparable fMRI studies. Bipolar
      diagnosed patients had a generally longer duration and/or later-peaking
      hemodynamic response in amygdala and numerous prefrontal cortex brain regions.
      Data are consistent with existing models of bipolar limbic hyperactivity, but the
      prolonged frontolimbic response more precisely details abnormalities recognized
      in previous studies. Prolonged hemodynamic responses were unrelated to stimulus
      type, task performance, or degree of residual mood symptoms, suggesting an
      important novel trait vulnerability brain dysfunction in bipolar disorder.
      Bipolar patients also failed to engage pregenual cingulate and left orbitofrontal
      cortex-regions important to models of automatic emotion regulation-while engaging
      a delayed dorsolateral prefrontal cortex response not seen in controls. These
      results raise questions about whether there are meaningful relationships between
      bipolar dysfunction of specific ventromedial prefrontal cortex regions believed
      to automatically regulate emotional reactions and the prolonged responses in more
      lateral aspects of prefrontal cortex. 

PMID- 23975277
TI  - Enhanced lignin biodegradation by a laccase-overexpressed white-rot fungus
      Polyporus brumalis in the pretreatment of wood chips.
AB  - The laccase gene of Polyporus brumalis was genetically transformed to overexpress
      its laccase. The transformants exhibited increased laccase activity and effective
      decolorization of the dye Remazol Brilliant Blue R than the wild type. When the
      transformants were pretreated with wood chips from a red pine (softwood) and a
      tulip tree (hardwood) for 15 and 45 days, they showed higher lignin-degradation
      activity as well as higher wood-chip weight loss than the wild type. When the
      wood chips treated with the transformant were enzymatically saccharified, the
      highest sugar yields were found to be 32.5 % for the red pine wood and 29.5 % for
      the tulip tree wood, on the basis of the dried wood weights, which were 1.6-folds
      higher than those for the wild type. These results suggested that overexpression
      of the laccase gene from P. brumalis significantly contributed to the
      pretreatment of lignocellulose for increasing sugar yields. 

PMID- 23975278
TI  - Expression of biologically active human recombinant interferon alpha 2b in human
      breast cancer cell line Bcap-37.
AB  - Human interferon alpha 2b (IFNalpha-2b) is a pleiotropic cytokine used to treat
      various viral diseases and cancers. Conventionally, recombinant human IFNalpha-2b
      used in clinics was produced by prokaryotic expression system, which always lack
      of enough biological activity due to limitations on proper folding and post
      translational modifications, so the eukaryotic expression system are becoming
      prevailing method for the production of recombinant proteins. In this study,
      human breast cancer cell Bcap-37 was firstly used as host for the expression of
      human IFNalpha-2b, with the expression vector pIRES2-IFN-EGFP, in which IFNalpha
      2b gene is under the control of CMV promoter. The expression of recombinant
      IFNalpha-2b was detected by Western blot and ELISA. Results showed that the
      concentration of the secreted recombinant IFNalpha-2b in culture medium was 435.7
      pg/mL/24 h. Biological activity of the recombinant IFNalpha-2b was assayed by
      detecting the expression of IFN-inducible genes, including MxA, OAS, PKR, and
      Caspase1 through QRT-PCR. Results demonstrated that recombinant IFNalpha-2b
      possess the biological activities. Compared to non-transgenic cells, the
      expression levels of the aforementioned four IFN-inducible genes were increased
      by 18.098-, 1.843-, 2.21-, and 3.066-folds, respectively. We got to a conclusion
      that the human breast cancer cell Bcap-37 could express bioactive recombinant
      IFNalpha-2b. 

PMID- 23975279
TI  - Refolding of laccase in dilution additive mode with copper-based ionic liquid.
AB  - Ionic liquids (ILs) are molten salts which do not crystallize at room
      temperature. Tunable physicochemical properties of ILs including hydrophobicity
      and polarity facilitate their applications in many biological processes. In this
      study, a copper-based IL was employed in order to enhance the refolding
      efficiency of laccase from Trametes versicolor which requires copper as a
      cofactor. When 1-ethyl-3-methylimidazolium trichlorocuprate ([EMIM][CuCl3]) was
      added to refolding buffer instead of urea, the laccase refolding yield was
      improved more than 2.7 times compared to the conventional refolding buffer which
      contains urea. When the refolding of laccase was carried out at different
      temperatures (4, 25, and 37  degrees C), the highest refolding yield was obtained
      at 25  degrees C. At low temperature, two conflicting effects, i.e., suppression
      of the aggregate formation and decrease of folding rate, influence the protein
      refolding. In contrast, a copper-based IL did not enhance the refolding of
      lysozyme, a non-copper-containing protein. From these results, we can conclude
      that this copper-based IL, [EMIM][CuCl3], was exclusively effective on the
      refolding process of a copper-containing protein.

PMID- 23975280
TI  - Biodegradable polycaprolactone (PCL) nanosphere encapsulating superoxide
      dismutase and catalase enzymes.
AB  - Biodegradable polycaprolactone (PCL) nanosphere encapsulating superoxide
      dismutase (SOD) and catalase (CAT) were successfully synthesized using double
      emulsion (w/o/w) solvent evaporation technique. Characterization of the
      nanosphere using dynamic light scattering, field emission scanning electron
      microscope, and Fourier transform infrared spectroscopy revealed a spherical
      shaped nanosphere in a size range of 812 +/- 64 nm with moderate protein
      encapsulation efficiency of 55.42 +/- 3.7 % and high in vitro protein release.
      Human skin HaCat cells were used for analyzing antioxidative properties of SOD-
      and CAT-encapsulated PCL nanospheres. Oxidative stress condition in HaCat cells
      was optimized with exposure to hydrogen peroxide (H2O2; 1 mM) as external stress
      factor and verified through reactive oxygen species (ROS) analysis using H2DCFDA
      dye. PCL nanosphere encapsulating SOD and CAT together indicated better
      antioxidative defense against H2O2-induced oxidative stress in human skin HaCat
      cells in comparison to PCL encapsulating either SOD or CAT alone as well as
      against direct supplement of SOD and CAT protein solution. Increase in HaCat
      cells SOD and CAT activities after treatment hints toward uptake of PCL
      nanosphere into the human skin HaCat cells. The result signifies the role of PCL
      encapsulating SOD and CAT nanosphere in alleviating oxidative stress.

PMID- 23975276
TI  - The perfect neuroimaging-genetics-computation storm: collision of petabytes of
      data, millions of hardware devices and thousands of software tools.
AB  - The volume, diversity and velocity of biomedical data are exponentially
      increasing providing petabytes of new neuroimaging and genetics data every year.
      At the same time, tens-of-thousands of computational algorithms are developed and
      reported in the literature along with thousands of software tools and services.
      Users demand intuitive, quick and platform-agnostic access to data, software
      tools, and infrastructure from millions of hardware devices. This explosion of
      information, scientific techniques, computational models, and technological
      advances leads to enormous challenges in data analysis, evidence-based biomedical
      inference and reproducibility of findings. The Pipeline workflow environment
      provides a crowd-based distributed solution for consistent management of these
      heterogeneous resources. The Pipeline allows multiple (local) clients and
      (remote) servers to connect, exchange protocols, control the execution, monitor
      the states of different tools or hardware, and share complete protocols as
      portable XML workflows. In this paper, we demonstrate several advanced
      computational neuroimaging and genetics case-studies, and end-to-end pipeline
      solutions. These are implemented as graphical workflow protocols in the context
      of analyzing imaging (sMRI, fMRI, DTI), phenotypic (demographic, clinical), and
      genetic (SNP) data. 

PMID- 23975281
TI  - Enhancing the cellulose-degrading activity of cellulolytic bacteria CTL-6
      (Clostridium thermocellum) by co-culture with non-cellulolytic bacteria W2-10
      (Geobacillus sp.).
AB  - The effect of a non-cellulolytic bacterium W2-10 (Geobacillus sp.) on the
      cellulose-degrading activity of a cellulolytic bacterium CTL-6 (Clostridium
      thermocellum) was determined using cellulose materials (paper and straw) in
      peptone cellulose solution (PCS) medium under aerobic conditions. The results
      indicated that in the co-culture, addition of W2-10 resulted in a balanced medium
      pH, and may provide the required anaerobic environment for CTL-6. Overall,
      addition of W2-10 was beneficial to CTL-6 growth in the adverse environment of
      the PCS medium. In co-culture with W2-10, the CTL-6 cellulose degradation
      efficiency of filter paper and alkaline-treated wheat straw significantly
      increased up to 72.45 and 37.79 %, respectively. The CMCase activity and biomass
      of CTL-6 also increased from 0.23 U ml(-1) and 45.1 MUg ml(-1) (DNA content) up
      to 0.47 U ml(-1) and 112.2 MUg ml(-1), respectively. In addition, co-culture
      resulted in accumulation of acetate and propionate up to 4.26 and 2.76 mg ml(-1).
      This was a respective increase of 2.58 and 4.45 times, in comparison to the
      monoculture with CTL-6.

PMID- 23975282
TI  - One-pot lipase-catalyzed aldol reaction combination of in situ formed
      acetaldehyde.
AB  - A facile tandem route to alpha,beta-unsaturated aldehydes was developed by
      combining the two catalytic activities of the same enzyme in a one-pot strategy
      for the aldol reaction and in situ generation of acetaldehyde. Lipase from Mucor
      miehei was found to have conventional and promiscuous catalytic activities for
      the hydrolysis of vinyl acetate and aldol condensation with in situ formed
      acetaldehyde. The first reaction continuously provided material for the second
      reaction, which effectively reduced the volatilization loss, oxidation, and
      polymerization of acetaldehyde, as well as avoided a negative effect on the
      enzyme of excessive amounts of acetaldehyde. After optimizing the process,
      several substrates participated in the reaction and provided the target products
      in moderate to high yields using this single lipase-catalyzed one-pot
      biotransformation. 

PMID- 23975283
TI  - Cytotoxicity evaluation and subcellular location of titanium dioxide nanotubes.
AB  - TiO(2) nanotubes (TiO(2)-NTs) are currently attracting a high interest because
      the intrinsic properties of TiO(2) provide the basis for many outstanding
      functional features. Herein, we focus on the cytotoxicity and sublocation of
      TiO(2)-NTs in neural stem cells (NSCs). The cytotoxicity of TiO(2)-NTs is
      investigated using the methyl tetrazolium cytotoxicity and reactive oxygen
      species assay, the apoptosis assay by flow cytometry. Cell viability assay shows
      that TiO(2)-NTs inside cells are nontoxic at the low concentration. A time
      dependent relationship is observed, while a dose-dependent relationship is seen
      only at the concentration higher than 150 MUg/ml. The uptake happens shortly
      after incubation with cells. TiO(2)-NTs can easily pass through the cell membrane
      and enter into the cells. The uptake amount is increased with prolonging
      incubation time and reach to maximum at 48 h. Transmission electron microscopy
      and confocal is used to study subcellular location of TiO(2)-NTs. It is found
      that TiO(2)-NTs traversed cell membrane and localized in many vesicles (endosomes
      and lysosomes) and cytoplasm. TiO(2)-NTs in NSCs firstly disperse or metabolism
      by lysosomal enzymes and then exocytosis from NSCs.

PMID- 23975284
TI  - Inferior dermal flap in immediate breast reconstruction.
AB  - BACKGROUND: The inferior dermal flap can be used in conjunction with implants or
      tissue expanders to avoid need for acellular dermal matrix in breast
      reconstruction and on occasion can serve as an alternative to an autologous flap
      by functioning as a reconstructed breast mound. Candidates for this procedure are
      women with high BMI or breast ptosis who desire a decrease in breast size at time
      of mastectomy with reconstruction. This procedure recruits the de-epithelialized
      excess skin inferiorly and laterally from a skin-sparing mastectomy and uses this
      to eliminate the need for acellular dermal matrix in a cost-conscious
      environment. METHODS: The skin-sparing mastectomy is performed, and the inferior
      skin flap is de-epithelialized to create the inferior dermal pedicle. A gel
      implant is placed retropectorally, and the inferior dermal flap is sutured to the
      inferior border of the pectoralis major muscle and laterally to a muscle-sparing
      serratus pedicle to provide support and coverage of the implant. RESULTS: We have
      performed this procedure in several patients and present a video outlining the
      technique of this procedure in a 54-year-old female diagnosed with left breast
      DCIS. Postoperative pictures taken at 6 weeks showed an excellent cosmetic result
      without complications. CONCLUSIONS: The inferior dermal flap is a simple and
      reproducible procedure that can reduce cost by eliminating the use of acellular
      dermal matrix. It provides an excellent cosmetic outcome in women undergoing
      mastectomy with large BMI and breast ptosis seeking reduction in breast size.

PMID- 23975285
TI  - Management of percutaneous core biopsy tract bleeding.

PMID- 23975286
TI  - Shared decision making in breast cancer: national practice patterns of surgeons.
AB  - BACKGROUND: The purpose of this study was to assess national practices of
      surgeons who treat breast cancer in order to identify opportunities to improve
      patient education. METHODS: In June 2012, the membership of the American Society
      of Breast Surgeons (ASBrS) (n = 2,818) was surveyed via email questionnaire to
      evaluate their current practice of shared decision making and informed consent
      for breast cancer patients. RESULTS: A total of 737 members (26 %) responded,
      including 384 breast surgeons and 306 general surgeons, 13 midlevel providers,
      and 25 other specialists. It was found that 90 % of surgeons spent more than 30
      min meeting with a new cancer patient, and of these, 30 % spent more than an
      hour. Surgeons who spent more than 1 h face-to-face with a new cancer patient
      reported higher levels of overall patient knowledge compared with those who spent
      less (mean = 3.80 vs. 3.64 of 5; p = 0.001). Also, 89 % of respondents reported
      using educational tools, of whom more than 90 % used written tools. In addition,
      65 % of members stated an interest in a free online educational tool if available
      and indicated a preference for a flexible tool that could be used by the patient
      alone or with a nurse. CONCLUSIONS: While practice patterns may vary, our results
      reveal that one-third of surgeons spend at least 1 h in consultation with a new
      breast cancer patient. More time spent translated to a higher perceived patient
      understanding of their disease and treatment options. Although the majority of
      surgeons currently use written materials, there was clear support for a free
      online educational tool.

PMID- 23975287
TI  - Axillary reverse mapping: a prospective study in women with clinically node
      negative and node positive breast cancer.
AB  - BACKGROUND: The primary aim of axillary reverse mapping (ARM) is to prevent
      lymphedema by preserving arm versus breast axillary lymphatics. Concerns
      regarding feasibility and oncologic safety have limited the adoption of the
      technique. This prospective study was undertaken to investigate ARM in clinically
      node negative and node positive breast cancer patients. METHODS: A total of 184
      patients underwent 212 ARM procedures: 155 sentinel lymph node biopsies (SLNB)
      without axillary lymph node dissection (ALND) (group 1) and 57 ALNDs with/without
      SLNB (group 2). ARM lymphatics were not preserved if they were a SLN, directly
      entered a SLN, or were within ALND boundaries during ALND. RESULTS: SLN with
      radioisotope alone was successful in 92 % of procedures (181 of 197). ARM
      identification was 47 % (73 of 155) in group 1. Criteria were met in 30 % (47 of
      155) for preservation, and 25 % (38 of 155) were preserved. Of those who met
      preservation criteria, 81 % (38 of 47) were preserved. In group 2, ARM
      identification was 72 % (41 of 57); 7 met criteria for preservation and were
      preserved. Of the ARM nodes, 10 % (22 of 212) were SLNs (crossover). ARM nodes
      contained metastatic disease in one crossover and two nonsentinel ARM nodes in
      clinically node positive patients with N2/N3 disease. CONCLUSIONS: ARM is a
      feasible technique for identification and preservation of axillary arm lymphatics
      with an acceptable incidence of SLN crossover. A larger sample size is needed to
      determine if ARM can reduce the incidence of lymphedema in patients undergoing
      SLNB alone and to confirm the absence of ARM metastases in clinically node
      negative patients undergoing ALND.

PMID- 23975288
TI  - The value of 6-month interval imaging after benign radiologic-pathologic
      concordant minimally invasive breast biopsy.
AB  - BACKGROUND: Current National Comprehensive Cancer Network guidelines recommend
      repeat imaging 6-12 months after a benign radiologic-pathologic concordant image
      guided breast biopsy. We hypothesized that interval imaging <12 months after
      benign concordant biopsy has a low cancer yield and increases health care costs.
      METHODS: An institutional review board-approved retrospective chart review
      identified 689 patients who underwent image-guided breast biopsy at Bryn Mawr
      Hospital between January and December 2010. Charts were evaluated for
      documentation of radiologic-pathologic concordance. RESULTS: Of 689 patients, 188
      (27 %) had malignant pathology, 3 (0.4 %) had nonbreast pathology, and 498 (72.3
      %) had benign pathology. Of 498 patients with benign findings, 44 (8.8 %)
      underwent surgical excision as a result of discordance, atypia, papillary lesion,
      or other benign finding. Of the remaining 454 patients who did not undergo
      excision, 337 (74.2 %) had documented radiologic-pathologic concordance. Interval
      imaging <12 months after benign biopsy was obtained in 182 (54.0 %) concordant
      patients. Five (2.7 %) patients had suspicious [American College of Radiology
      Breast Imaging-Reporting and Data System (BI-RADS) 4] findings on follow-up
      imaging. Only one breast cancer was identified, representing 0.5 % (95 %
      confidence interval 0-3.4) of all benign concordant patients undergoing interval
      imaging. The cost of detecting a missed cancer with interval imaging after benign
      concordant biopsy was $41,813.77 in this cohort. CONCLUSIONS: Interval imaging
      performed <12 months after benign concordant breast biopsy demonstrated a low
      yield for the detection of breast cancer and resulted in increased health care
      costs. Our data support the policy for discontinuation of routine interval
      imaging after benign concordant biopsy.

PMID- 23975289
TI  - Selection criteria for postmastectomy radiotherapy in t1-t2 tumors with 1 to 3
      positive lymph nodes.
AB  - BACKGROUND: Postmastectomy radiotherapy (PMRT) is well established in patients
      with >=4 positive axillary lymph nodes (ALN); indications in 1 to 3 positive ALN
      remains controversial. We examined clinicopathologic criteria used for PMRT
      selection and compared locoregional recurrence (LRR), recurrence-free survival
      (RFS), and overall survival (OS) among patients with and without PMRT. METHODS:
      Between 1995 and 2006, a total of 1,331 patients with T1-T2 tumors and 1 to 3
      positive ALN underwent mastectomy. We excluded T3/T4 tumors and neoadjuvant
      chemotherapy; we analyzed 1,087 patients (924 without PMRT, 163 with PMRT). Chi
      square testing compared clinicopathologic features between groups. The Kaplan
      Meier method and Cox regression analysis examined the association between PMRT
      and LRR, RFS, and OS. RESULTS: PMRT patients were more likely to be <=50 years
      old (p = 0.001) and to have larger tumors (p = 0.01), disease of a higher
      histologic grade (p = 0.03), lymphovascular invasion (LVI) (p < 0.0001), a
      greater number of positive ALN (p < 0.0001), extranodal invasion (p < 0.0001),
      and macroscopic ALN metastases (p < 0.0001). With a median follow-up of 7 years,
      PMRT and no-PMRT groups were similar in LRR (p = 0.57), RFS (p = 0.70), and OS (p
      = 0.28). On multivariate analysis of the no-PMRT group, age <=50 years (p =
      0.002) and presence of LVI (p < 0.0001) were associated with LRR. Stratified by
      age and LVI, patients <=50 years old and with LVI had the highest 5-year LRR,
      10.1 versus 1.1 %, than in patients >50 years old without LVI (p < 0.001).
      CONCLUSIONS: By using clinicopathologic features, clinicians delivered PMRT to a
      select group of patients with T1-T2 tumors and 1 to 3 positive ALN, resulting in
      similarly low rates of 5-year LRR. Among patients not receiving PMRT, age <=50
      years and LVI were associated with increased LRR rates and warrant PMRT
      consideration.

PMID- 23975290
TI  - Improving breast diagnostic services with a Rapid Access Diagnostic and Support
      (RADS) program.
AB  - BACKGROUND: The diagnostic phase of care is an anxiety-provoking and stressful
      experience for the potential breast cancer patient. A multidisciplinary team of
      breast cancer specialists embarked on a new initiative to pilot a Rapid Diagnosis
      and Support (RADS) Clinic to coordinate the diagnostic workup and nursing support
      for patients with a high probability of breast cancer. METHODS: Consecutive
      patients with an initial diagnostic imaging classified as BI-RADS 5 were invited
      to participate in this 1-year prospective study. Coordination of diagnostic
      imaging workup and nursing support were provided by a nurse navigator. Wait times
      were evaluated at several intervals of care. Satisfaction surveys were given to
      study participants and compared to scores from patients who did not go through
      RADS clinic. RESULTS: A total of 211 patients participated in the RADS clinic.
      Biopsy wait times improved from a mean of 7 to 3 days (p < 0.001), pathology from
      3.9 to 3.3 days (p < 0.001), surgical consultation from 16.1 to 5.9 days (p <
      0.001), and operative wait times from 31.5 to 24.1 days (p = 0.042). There was a
      95.3 % satisfaction rate with the RADS clinic with significantly improvement in
      patients' sense of an understanding of the treatment plan (p = 0.031), timeliness
      of tests (p = 0.045), and timeliness of results (p = 0.0419). CONCLUSIONS: The
      RADS clinic significantly improved diagnostic wait times and satisfaction scores
      for patients with a high probability of diagnosis of breast cancer and can serve
      as an innovative service delivery model for other breast care centers.

PMID- 23975291
TI  - Revisiting the free nipple graft: an opportunity for nipple sparing mastectomy in
      women with breast ptosis.
AB  - OBJECTIVE: Nipple areolar complex (NAC) sparing mastectomy improves the cosmetic
      outcome of patients with breast cancer. However, women with significant breast
      ptosis are not candidates for this technique due toexcessive skin flap length and
      ensuing risk of NAC ischemia.1 (-) 3 We report a novel technique using free
      nipple graft during skin sparing mastectomy for patients with significant ptosis
      while concurrently maintaining oncologic integrity. DESIGN: Case series. SETTING:
      Community and tertiary care hospital practices. PATIENTS: Women with breast
      cancer desiring NAC preservation who are otherwise candidates for nipple sparing
      mastectomy, but with significant breast ptosis that precludes NAC viability. All
      women underwent immediate, autologous breast reconstruction. INTERVENTIONS:
      Bilateral and unilateral free nipple grafts were harvested, placed on ice during
      skin sparing mastectomy and free flap reconstruction, grafted at the conclusion
      of the case and secured with a bolster. OUTCOME MEASURES: Full or partial NAC
      preservation, ischemia time, local wound complications at NAC grafting site,
      pathologic outcomes. RESULTS: A total of three patients underwent free nipple
      grafting at the time of skin sparing mastectomy and free or pedicled flap for
      breast cancer between March and September 2012. Of five total nipple grafts, one
      had partial NAC loss but did not require operative debridement. Pathologic review
      of areolar tissue removed during intraoperative defatting of free nipple graft
      demonstrated residual duct epithelium. CONCLUSIONS: Women with significant breast
      ptosis that would preclude them from NAC sparing mastectomy can successfully
      preserve their NAC using a free nipple graft. Duct epithelium present in defatted
      tissue during preparation of the free nipple graft suggests that oncologic
      integrity can also be maintained.

PMID- 23975292
TI  - Is postexcision, preradiation mammogram necessary in patients after breast
      conserving surgery with negative margins.
AB  - BACKGROUND: In women with breast cancer and calcifications, controversy exists
      over the need for postexcision/lumpectomy, preradiation mammogram (PEM) after
      breast-conserving surgery (BCS). Further, the need for excision of remaining or
      suspicious calcifications after PEM when surgical margins are negative is
      unclear. We sought to characterize the utility of PEM hypothesizing that its
      value in directing the need for additional surgery is minimized after achieving
      negative surgical margins. METHODS: We identified 524 women with breast cancer
      and calcifications treated with BCS with negative margins between 1996 and 2011.
      RESULTS: PEM was performed in 112 of 524 (21 %) women, with residual
      calcifications identified in 10 of 112 (9 %); of these, 2 of 112 (1.8 %) had
      residual disease. Local recurrence occurred in 4 of 112 (4 %) patients, none of
      whom had residual calcifications identified on PEM. The remaining 412 of 524 (79
      %) women did not have PEM but had a postradiation mammogram 6 to 12 months after
      treatment identifying calcifications in 19 (5 %) women. Tissue diagnosis was
      benign in 14 women and was not pursued in the remaining 5. Local recurrence
      occurred in 13 (3 %) patients, none of whom had calcifications on the new post
      radiation baseline mammogram. CONCLUSIONS: Mammographically apparent
      calcifications representing residual disease occur infrequently after BCS with
      negative margins. The value of PEM may be to document the new radiographic
      baseline but should not be required to ensure adequate surgery. Radiation plays
      an integral role in sterilization of the remaining breast tissue after BCS.

PMID- 23975293
TI  - Neoareolar wise pattern reduction in patients requiring central partial
      mastectomy.
AB  - BACKGROUND: Oncoplastic surgery integrates breast cancer resection with tissue
      transfer techniques to preserve breast cosmesis. With the novel methods developed
      in the oncoplastic movement, we are capable of performing larger resections with
      clear margins while minimizing the cosmetic deformity caused by more traditional
      surgical techniques. Central and retroareolar breast cancers continue to be a
      cosmetic challenge because removal of the central portion of the breast can be
      particularly deforming. METHODS: An inferior pedicle Wise pattern reduction
      mammoplasty is performed. The inferior pedicle is de-epithelized except for a
      circular disc of skin superiorly, which will become the neoareola. The breast
      cancer is removed along with the nipple-areolar complex (NAC). Part of the NAC
      may be preserved if tumor resection can be performed with sufficient margins. A
      standard reduction is performed, removing more tissue as indicated by cosmetic
      need. The reduction is completed in standard fashion using the neoareola as a
      replacement for the previously removed NAC. RESULTS: The video demonstrates the
      feasibility of this technique, highlighting both preservation of breast shape and
      contour, and creation of a substitute for the NAC. DISCUSSION: Complex reduction
      techniques have been reported in the literature as feasible options for breast
      conservation surgery. The neoareolar Wise pattern reduction mammoplasty offers an
      option that allows for oncologically sound cancer surgery while simultaneously
      preserving cosmesis.

PMID- 23975294
TI  - Trends in radiotherapy after breast-conserving surgery in elderly patients with
      early-stage breast cancer.
AB  - BACKGROUND: The benefit of adjuvant radiotherapy (RT) in elderly breast cancer
      patients is debatable. The purpose of this study was to evaluate trends in RT
      rates after breast-conserving surgery. METHODS: Breast cancer patients >=70 years
      treated from 2000 to 2009 were identified using the Surveillance, Epidemiology,
      and End Results (SEER) database. Patients were estrogen receptor positive with
      negative or unknown lymph node status. Trends in RT recommendation over years
      were evaluated with the Jonckheere-Terpstra test. Multiple logistic regression
      and Cox proportional hazard tests were used to determine factors associated with
      radiation recommendation and survival. RESULTS: Of 46,581 patients, 31,989 (68.7
      %) were recommended RT and 14,592 (31.3 %) were not. The recommendation for RT
      decreased from 70.3 % in 2000 to 67.4 % in 2009 (p < 0.0001). Seven of 18
      registries exhibited decreased radiation recommendation rates, and 4 of 18
      exhibited an increase. Recommendation of RT was associated with earlier year of
      diagnosis, younger age, Asian/Pacific Islander race, and negative lymph nodes.
      Predictors of worse survival were no radiation [hazard ratio (HR) 1.68, 95 %
      confidence interval (CI) 1.61-1.75], no nodes examined (HR 1.83, 95 % CI 1.75
      1.91), large (>2-5 cm) tumor size (HR 2.02, 95 % CI 1.86-2.19), older age (80+,
      HR 2.38, 95 % CI 2.25-2.53), and black race (HR 1.13, 95 % CI1.03-1.23).
      CONCLUSIONS: Rates of radiation recommendation in the elderly have been steadily
      decreasing without appreciable acceleration in this decline. This trend was not
      consistent across all registries. Continued research is necessary to assess
      differences in clinical practice and its impact on patient outcomes.

PMID- 23975295
TI  - Management of contralateral axillary sentinel lymph nodes detected on
      lymphoscintigraphy for breast cancer.
AB  - BACKGROUND: Detection of a contralateral axillary sentinel lymph node (SLN)
      during lymphoscintigraphy for breast cancer is rare, and its significance and
      management are unclear. The purpose of this study was to review our experience
      and analyze our results together with similar patients in the literature to
      identify common characteristics and propose a management strategy. METHODS: A
      PubMed search was performed for articles describing patients in whom
      contralateral axillary drainage was identified on lymphoscintigraphy.
      Additionally, a chart review was performed of all patients who had
      lymphoscintigraphy for breast cancer at our institution. RESULTS: At our
      institution, two of 988 (0.3 %) consecutive patients were identified with
      contralateral axillary drainage on lymphoscintigraphy. Twenty-seven publications
      describing 105 patients with contralateral axillary drainage were found. This
      comprised our study group of 107 patients. Lymphoscintigraphy patterns varied
      depending on the history and type of prior surgery. A history of chest/axillary
      surgery was significantly associated with absence of an ipsilateral SLN (p <
      0.05). This was observed in 84.2 % of patients with prior axillary lymph node
      dissection versus 33.3 % with prior SLN. Contralateral SLN biopsy was attempted
      in 85 patients (79.4 %); 22 (20.6 %) were positive for tumor. In 17 patients
      (15.9 %), the contralateral node was the only positive SLN. CONCLUSIONS: These
      findings suggest that contralateral uptake on lymphoscintigraphy, though rare
      (0.2 %), is clinically significant and such nodes should undergo excision.
      Because contralateral uptake is significantly associated with prior
      chest/axillary surgery, routine lymphoscintigraphy should be considered in this
      group, as it has potential to change disease stage and management.

PMID- 23975296
TI  - Increasing eligibility for nipple-sparing mastectomy.
AB  - BACKGROUND: Eligibility for nipple-sparing mastectomy (NSM) varies widely on the
      basis of patient and tumor factors. METHODS: Review of patients undergoing NSM
      from June 2007 to December 2012 at our institution was performed. Patient and
      tumor characteristics, complications, and recurrences were collected. NSM from
      2007 to 2010 and 2011 to 2012 were compared to assess trends in eligibility and
      outcomes over time. RESULTS: NSM was performed on 645 breasts in 370 patients.
      Indications were risk reduction in 330 (51.2 %), invasive cancer in 226 (35.0 %),
      and ductal carcinoma-in situ in 89 (13.8 %) breasts. Fifty-one (13.8 %) patients
      had positive lymph nodes. Twenty-seven (7.3 %) patients received neoadjuvant
      chemotherapy. Forty-eight (7.4 %) breasts had prior radiotherapy. Total nipple
      necrosis occurred in 11 (1.7 %) breasts. Twenty-four (3.7 %) breasts had nipples
      removed as a result of positive subareolar/nipple margins. At 22 months' mean
      follow-up, local recurrence occurred in 4 of 156 (2.6 %) breasts operated on for
      cancer through 2011. No recurrences involved the nipple. NSM performed in 2011
      2012 (n = 475) compared to 2007-2010 (n = 170), were more often for cancer, in
      patients with higher body mass index, and on larger breasts (p < 0.001). There
      was no significant difference in total nipple necrosis rates between groups.
      Nipple loss due to positive subareolar/nipple margins was significantly less in
      2011-2012 (p = 0.027). CONCLUSIONS: Eligibility for NSM has expanded to include
      women with higher body mass index and larger breasts, with no increase in nipple
      loss due to ischemia. Rates of positive subareolar margins have decreased over
      time, even though NSM is being performed more frequently for cancer, suggesting
      improved patient selection.

PMID- 23975297
TI  - Axillary surgery among estrogen receptor positive women 70 years of age or older
      with clinical stage I breast cancer, 2004-2010: a report from the National Cancer
      Data Base.
AB  - BACKGROUND: Randomized trials have not demonstrated a survival benefit for
      axillary dissection in the elderly, but the use of axillary staging for women 70
      years of age and older remains controversial. METHODS: We utilized the National
      Cancer Data Base to study the use of axillary staging from 2004 to 2010 on
      102,026 clinically node-negative and estrogen receptor-positive cases of pT1N0
      tumors. Chi-square and logistic regression models were used to determine the
      trends and factors related to axillary staging. RESULTS: Axillary nodes were
      examined in 88.9 % of the total cohort, and the trend significantly increased
      from 87.7 % in 2004 to 89.2 % in 2010. A total of 77.2 % of patients underwent
      lumpectomy and 22.8 % mastectomy, with 87.0 % of lumpectomy patients undergoing
      axillary staging compared to 95.5 % of mastectomy patients. Predictors of
      axillary staging examined were age, comorbidity, income, histology, grade,
      facility type, facility location, and population density. The strongest
      independent predictor of axillary staging was age: 96.0 % of women aged 70-75
      years underwent axillary staging, versus 92.3 % of women 75-80 years old, 83.2 %
      of women 80-85 years old, 66.5 % of women 86-90 years old, and 45.6 % of women
      >90 years old. Patients treated at academic/research facilities were 18.5 % less
      likely (odds ratio 0.81, 95 % confidence interval 0.76-0.87) than community
      cancer programs to undergo axillary staging. There was significant regional
      variation among U.S. Census regions: patients treated in the Midwest were 3.8
      times more likely to undergo axillary staging than those treated in the
      Northeast. CONCLUSIONS: Despite data indicating decreased utility, axillary
      staging remains overutilized in women with advancing age.

PMID- 23975298
TI  - Accelerated partial-breast irradiation versus whole-breast irradiation for early
      stage breast cancer patients undergoing breast conservation, 2003-2010: a report
      from the national cancer data base.
AB  - BACKGROUND: Previous studies have demonstrated an increase in the utilization of
      accelerated partial-breast irradiation via brachytherapy (APBI-b), but larger,
      more contemporary studies examining overall APBI use are lacking. METHODS: A
      total of 575,438 nonneoadjuvant American Joint Committee on Cancer stage 0 to II
      breast conservation patients were selected from the National Cancer Data Base
      from 2003 to 2010 who underwent either whole-breast irradiation or APBI. RESULTS:
      Overall, 59,396 patients (10.3 %) underwent APBI. The use of APBI for the entire
      cohort increased from 3.4 % in 2003 to 12.8 % (p < 0.001) in 2008 and then
      decreased to 12.4 % in 2010. Three-dimensional conformal radiation increased from
      0.8 to 2.2 %, intensity-modulated radiotherapy increased from 0.7 to 1.3 %, and
      brachytherapy (APBI-b) increased from 2.0 to 8.9 %. The most significant factors
      associated with APBI use were patient age and facility location. Patients 80-89
      years old were 3.8 times more likely to undergo APBI compared to patients 30-39
      years old (odds ratio [OR] 3.77, 95 % confidence interval [CI] 3.45-4.10, p <
      0.001). Patients living in the West census region were 2.0 times more likely to
      undergo APBI compared to patients living in the Northeast (OR 2.0, 95 % CI 1.93
      2.15, p < 0.001). Using the American Society of Radiation Oncology (ASTRO)
      guidelines, among patients with noninvasive cancer who received APBI, 95.6 % were
      categorized as "cautionary" and 4.4 % as "unsuitable." Of the invasive patients,
      43.8 % were categorized as "suitable," 47.0 % as "cautionary," and 9.2 % as
      "unsuitable." CONCLUSIONS: The utilization of APBI has stabilized at
      approximately 12 % starting in 2008. The majority of APBI is delivered using APBI
      b, with patient age being the most significant factor associated with APBI use.

PMID- 23975299
TI  - Is there a correlation between breast cancer molecular subtype using receptors as
      surrogates and mammographic appearance?
AB  - BACKGROUND: The identification of distinct molecular subtypes has changed breast
      cancer management. The correlation between mammographic appearance and molecular
      subtype for invasive breast cancer has not been extensively studied. METHODS: A
      retrospective review of our prospectively collected database was performed to
      evaluate the mammographic appearance and molecular subtypes of all cases of
      invasive breast cancers diagnosed between 2003 and 2010. RESULTS: There were 985
      cases of invasive breast cancer with complete data on receptor status and
      mammographic appearance. The most common mammographic finding was a mass (61 %),
      and the most common molecular subtype was ER/PR positive, HER2 negative (71 %).
      On univariate analysis, race, stage, and histology were all significantly
      associated with molecular subtype. On multivariate analysis, the luminal
      molecular type was associated with architectural distortion [odds ratio (OR) 4.3,
      95 % CI 1.3-14.1]; HER2 positive cancers, either with or without ER/PR
      expression, were more likely to be associated with mammographic calcifications
      (OR 2.8 and 3.1, respectively; 95 % CI 1.7-4.8 and 1.7-5.5); and triple negative
      cancers were most likely to be associated with a mammographic mass (OR 2.5; 95 %
      CI 1.4-4.4). CONCLUSIONS: We observed several characteristic associations between
      molecular subtype and mammographic appearance. Improved understanding of these
      associations may help guide clinical decision making and provide information
      about underlying tumor biology.

PMID- 23975300
TI  - Incidence and predictors of neuropathic pain following breast surgery.
AB  - PURPOSE: Neuropathic pain (NPP) following breast surgery extends morbidity in the
      postoperative period. The incidence and etiology of postoperative NPP remains
      unclear and under-reported in literature. This study aims to define the incidence
      of neuropathic pain following breast surgery and to identify patient
      characteristics that are predictors for developing postoperative NPP. METHODS:
      Consecutive female patients undergoing breast resection surgery over a 5-year
      period (2008-2012) with 1-year minimum follow-up were included in this single
      center study. Retrospective chart review was performed to identify patient
      specific characteristics including the development of post-operative NPP. Data
      was analyzed using univariate and multivariate logistic regression. RESULTS: A
      total of 470 patients were identified for study inclusion. The incidence of
      postoperative NPP was 14.7 % (69 of 470). Significant predictors for the
      development of postoperative NPP in the univariate analyses included history of
      diabetes mellitus, diabetic neuropathy, or fibromyalgia, concomitant axillary
      surgery, axillary node dissection, and taxane-based chemotherapy regimen.
      Multivariate analysis identified African American race [odds ratio (OR) = 1.78;
      95 % CI = 1.01-3.17; p = 0.05), history of diabetes mellitus (OR = 1.98; 95 % CI
      = 1.0-3.74; p = 0.01) or fibromyalgia (OR = 2.75; 95 % CI = 1.13-6.69; p = 0.03),
      and taxane-based chemotherapy regimen (OR = 2.85; 95 % CI = 1.23-6.58; p = 0.01)
      as being independently associated with the development of postoperative NPP.
      CONCLUSIONS: NPP is a significant risk following breast surgery. African American
      race, history of either diabetes mellitus or fibromyalgia, and treatment with
      taxane-based chemotherapy regimens are all associated with an increased risk of
      NPP.

PMID- 23975301
TI  - Geographic and temporal trends in the management of occult primary breast cancer:
      a systematic review and meta-analysis.
AB  - BACKGROUND: Management of occult primary breast cancer (OPBC), including the role
      of magnetic resonance imaging (MRI), is controversial. We conducted a pooled
      analysis of OPBC patients and a meta-analysis of MRI accuracy in OPBC in order to
      elucidate current practices. METHODS: A literature search yielded 201 studies.
      Patient-level data for clinically/mammographically OPBC from studies published
      after 1993 and from our institution were pooled; logistic regression examined
      associations between patient/study data and outcomes, including treatments and
      recurrence. We report adjusted odds ratios (OR) and 95 % confidence intervals (95
      % CI) significant at 2-tailed p < 0.05. Meta-analysis included data for patients
      who received MRIs for workup of clinically/mammographically OPBC. We report
      pooled sensitivity and specificity with 95 % CIs. RESULTS: The pooled analysis
      included 92 patients (15 studies [n = 85] plus our institution [n = 7]). Patients
      from Asia were more likely to receive breast surgery (OR = 5.98, 95 % CI = 2.02
      17.65) but not chemotherapy (OR = 0.32, 95 % CI = 0.13-0.82); patients from the
      United States were more likely to receive chemotherapy (OR = 13.08, 95 % CI =
      2.64-64.78). Patients from studies published after 2003 were more likely to
      receive radiotherapy (OR = 3.86, 95 % CI = 1.41-10.55). Chemotherapy recipients
      were more likely to have distant recurrence (OR = 9.77, 95 % CI = 1.10-87.21).
      More patients with positive MRIs received chemotherapy than patients with
      negative MRIs (10 of 12 [83.3 %] vs 5 of 13 [38.5 %]; p = 0.0414). In the MRI
      accuracy meta-analysis (10 studies, n = 262), pooled sensitivity and specificity
      were 96 % (95 % CI = 91-98 %) and 63 % (95 % CI = 42-81 %), respectively.
      CONCLUSIONS: OPBC management varied geographically and over time. We recommend
      establishing an international OPBC patient registry to facilitate longitudinal
      study and develop global treatment standards.

PMID- 23975302
TI  - Treatment efficacy with accelerated partial breast irradiation (APBI): final
      analysis of the American Society of Breast Surgeons MammoSite((r)) breast
      brachytherapy registry trial.
AB  - BACKGROUND: The purpose of this study was to examine data on treatment efficacy,
      cosmesis and toxicities for the final analysis of the American Society of Breast
      Surgeons MammoSite((r)) breast brachytherapy registry trial. METHODS: A total of
      1,449 cases of early-stage breast cancer underwent breast conserving therapy. The
      single-lumen MammoSite((r)) device was used to deliver accelerated partial breast
      irradiation (APBI) (34 Gy in 3.4 Gy fractions). Of these, 1,255 cases (87 %) had
      invasive breast cancer (IBC) and 194 cases had DCIS. Median follow-up was 63.1
      months with 45 % of all patients having follow-up of 6 years or longer. RESULTS:
      There were 41 cases (2.8 %) that developed an ipsilateral breast tumor recurrence
      (IBTR) for a 5-year actuarial rate of 3.8 % (3.7 % for IBC and 4.1 % for DCIS).
      Tumor size (odds ratio [OR] = 1.1, p = 0.03) and estrogen receptor negativity (OR
      = 3.0, p = 0.0009) were associated with IBTR, while a trend was noted for
      positive margins (OR = 2.0, p = 0.06) and cautionary/unsuitable status compared
      with suitable status (OR = 1.8, p = 0.07). The percentage of patients with
      excellent/good cosmetic results at 60, 72, and 84 months was 91.3, 90.5, and 90.6
      %, respectively. The overall rates of fat necrosis and infections remained low at
      2.5 and 9.6 % with few late toxicity events beyond 2 years. The overall
      symptomatic seroma rate was 13.4 and 0.6 % beyond 2 years. CONCLUSIONS: The final
      analysis of treatment efficacy, cosmesis, and toxicity from the American Society
      of Breast Surgeons MammoSite((r)) breast brachytherapy registry trial confirms
      previously noted excellent results and compares favorably with other forms of
      APBI with similar follow-up and to outcomes seen in selected patients treated
      with whole breast irradiation.

PMID- 23975303
TI  - Undertreatment of thick head and neck melanomas: an age-based analysis.
AB  - PURPOSE: To determine U.S. treatment patterns for pathologic staging practices in
      patients with thick head and neck melanomas (HNM). METHODS: Patients with thick
      HNM without clinical evidence of in-transit, regional, or distant metastatic
      spread at presentation were identified from the Surveillance Epidemiology and End
      Results database. Treatment trends for patients were summarized, and univariate
      and multivariate analyses were performed to identify associations between varying
      practice patterns. RESULTS: A total of 1,230 patients with HNM meeting the
      inclusion criteria were identified. Surgical staging procedures were utilized in
      53.5 %, including both sentinel lymph node biopsy (37 %) and elective neck
      dissection (16 %). Patients undergoing a surgical staging procedure were younger
      (64 vs. 77 years, p < 0.001) with smaller tumors (6.3 vs. 6.6 mm, p = 0.008). The
      rate of occult nodal disease was 22 % in patients undergoing a surgical staging
      procedure. The presence of a positive regional node in this subgroup of patients
      was associated with a significant reduction in disease-specific (44 vs. 59
      months, p < 0.001) and overall survival (40 vs. 53 months, p < 0.001) on
      univariate analysis. On multivariate analysis, the presence of a positive node
      was the most significant factor for reduced overall survival (hazard ratio 2.36,
      95 % confidence interval 1.71-3.23) and disease-specific survival (hazard ratio
      2.84, 95 % confidence interval 1.99-4.06). CONCLUSIONS: Pathologic staging
      procedures provide independent prognostic information for patients with thick
      HNM. Despite this, current practice patterns demonstrate underutilization,
      particularly in elderly patients. Further work is needed to address the barriers
      to pathologic staging implementation in patients with thick HNM.

PMID- 23975304
TI  - Nipple skin-sparing mastectomy is feasible for advanced disease.
AB  - BACKGROUND: Skin-sparing mastectomy (SSM) or nipple skin-sparing mastectomy
      (NSSM) are procedures commonly offered as part of the surgical treatment for
      breast cancer. Each involves a mastectomy with preservation of the skin overlying
      the breast (in SSM) and often also the skin overlying the nipple-areolar complex
      (NSSM). At the time of mastectomy, immediate reconstruction with a tissue
      expander or implant is performed for a more favorable cosmetic outcome. Until
      now, these procedures have been reserved for low-risk patients and are rarely
      offered to patients with advanced disease where neoadjuvant chemotherapy and
      postmastectomy radiation are a planned part of the treatment. We report our
      experience of SSM and NSSM in such high-risk patients. METHODS: This
      retrospective study from 2001 to 2012 evaluates the outcomes of 527 patients who
      underwent SSM or NSSM. Sixty patients with advanced disease who underwent
      neoadjuvant chemotherapy followed by SSM or NSSM with immediate reconstruction
      and subsequent radiotherapy (RT) were identified. The cosmetic and oncologic
      outcomes of this patient group were noted. RESULTS: A total of 527 patients in
      our study group had a total of 1,035 skin-sparing mastectomies (558 NSSM and 477
      SSM; 444 patients with bilateral and 83 with unilateral procedures). Of the 60
      patients with locally advanced disease, 39 underwent NSSM and 21 underwent SSM.
      All patients received RT to the diseased side. Mean age of the group was 50.2 +/-
      10.8 years, with a range of 27-75 years for NSSM and 29-73 years for SSM. The
      lymph node status was positive in 71.8 % with an average tumor size of 3.8 +/-
      2.5 cm. The overall radiation-induced complication rate was 38.1 % (8 of 21) in
      the SSM group and 30.8 % (12 of 39) in the NSSM group. Wound infections and
      tissue necrosis occurred at a rate of 16.7 %. The implant was removed in 5 % of
      these cases. Capsular contracture occurred at a rate of 10.2 %. Radiation-related
      nonbreast complications occurred in 6.7 % of the cases. Examples of these
      radiation-related nonbreast complications included radiation pneumonitis,
      stenosis of the superior vena cava requiring venoplasty and severe atypical chest
      pain thought to be consistent with osteochondritis. The locoregional recurrence
      rate (median follow-up of 18 months) was 14.3 % (3 of 21) in the SSM group and
      10.3 % (4 of 39) in the NSSM group. CONCLUSIONS: SSM and NSSM have been offered
      to patients with relatively low-risk breast cancer as oncologically safe while
      affording superior cosmesis with one-step immediate reconstruction. Our series
      demonstrates that either procedure can be offered to patients with more advanced
      cancers requiring postoperative RT. The complication rates are comparable to
      those reported for patients undergoing RT after traditional mastectomies.

PMID- 23975305
TI  - Round block technique without cerclage in breast-conserving surgery.
AB  - BACKGROUND: Round block technique is a unique breast resection through
      periareolar doughnut incision. However, it is more technically challenging and
      time consuming. We simplified the procedure by exclusion of round block cerclage.
      The purpose of this study was to introduce our round block technique without
      cerclage and to evaluate the results of oncological and cosmetic outcomes.
      METHODS: A total of 92 patients with centrally located breast cancer were treated
      with breast-conserving surgery using round block technique at Samsung Medical
      Center from July 2009 to May 2012. All patients had a small breast defect with
      excised breast volume less than 20 % compared to the total breast volume. We
      minimized the extent of skin removal and used simple interrupted inverted
      intradermal sutures without cerclage in doughnut closure. Patient's cosmetic
      satisfaction was assessed by subjective questionnaires at least 6 months after
      the operation. RESULTS: The median size of tumors was 1.7 cm (range 0.5-5.0 cm).
      The average distance of the tumors from the nipple was 2.0 cm (range 0.0-4.0 cm)
      on sonogram and most of the tumors were located upper breast (82.6 %). The median
      operative time was 101.5 min (range 55-180), including axillary surgeries. Median
      follow-up was 12.0 months (range 2-36), and none of patients have developed local
      recurrence. Up to the longest 3 years of follow-up, favorable cosmetic results
      have been found in patients treated with round block technique. CONCLUSIONS:
      Round block without cerclage is technically easy and feasible for centrally
      located breast tumors with favorable cosmetic results.

PMID- 23975306
TI  - DCIS treated with excision alone using the National Comprehensive Cancer Network
      (NCCN) guidelines.
AB  - BACKGROUND: In 2008, the NCCN published guidelines allowing low-risk DCIS
      patients to be treated by excision alone. The goal of this study was to determine
      local and distant recurrence and breast-cancer specific survival in patients with
      DCIS that meet NCCN criteria and are treated with excision alone. METHODS: A
      prospective, single institution database was analyzed for patients with the
      following: pure ductal carcinoma in situ (no microinvasion), tumor extent 20 mm
      or less, age >=50 years, margin width >=2 mm, and nuclear grade 1 or 2 (non-high
      grade). Patients were treated with excision alone. Kaplan-Meier analysis was used
      to determine recurrence and survival rates. RESULTS: A total of 205 patients were
      treated with excision alone. The median age was 59 years. The median time of
      follow-up was 51 months. The median extent of disease was 8 mm. There were a
      total of nine local recurrences. The 6-year probability of local recurrence was
      6.6 %. The 12-year probability of local recurrence was 7.8 %. The 12-year breast
      cancer-specific survival probability was 100 %. CONCLUSIONS: The 12-year local
      recurrence rate for DCIS patients in NSABP Protocol B-17 treated with excision
      alone was 32 %, and for excision plus radiation therapy, it was 16 %. In this
      study, retrospectively applying the NCCN Guidelines to our patients, the 12-year
      local recurrence rate for excision alone was 7.8 %. Patients with a low risk of
      local recurrence, if treated by excision alone, can be safely selected using the
      NCCN Guidelines.

PMID- 23975307
TI  - Adjuvant endocrine therapy for the surgeon: options, side effects, and their
      management.
AB  - Adjuvant endocrine therapy is often advised for women with hormone receptor
      positive breast cancer. In premenopausal women, tamoxifen is the primary
      endocrine therapy option since aromatase inhibitors (AIs) are contraindicated in
      patients with residual ovarian function. The benefit of ovarian
      ablation/suppression in premenopausal patients remains controversial. In
      postmenopausal ER positive patients, treatment with an AI alone, switching
      strategies with an AI and tamoxifen, or extended therapy with an AI after 5 years
      of tamoxifen are superior to 5 years of tamoxifen alone. While the data
      supporting the use of endocrine therapy for ER positive breast cancer is clear,
      adverse effects occur with variable frequency and severity. The intensity and
      severity of the most common endocrine therapy adverse effects are mild to
      moderate for the majority of women, and serious life-threatening adverse effects
      are uncommon. However, compliance issues are often larger than recognized. Good
      communication with patients is critical to address concerns and symptoms, and
      more research is needed to identify effective methods to minimize treatment side
      effects.

PMID- 23975308
TI  - Ethical issues of participant recruitment in surgical clinical trials.
AB  - Although the historical background of ethical principles of human subjects
      research are the same for surgery and nonsurgical fields, surgical clinical
      trials raise several specific ethical issues. Placebo arms in surgical trials are
      problematic because the closer the sham surgery is to a real operation, the
      greater the risks for subjects. In order to ethically enter subjects into a
      clinical trial, a researcher must have equipoise-that is, uncertainty about which
      treatment arm is more effective. Surgeons must diligently maintain skepticism
      about whether new treatments are actually better until objective data are
      available. The dynamic of informed consent between surgeons and patients may be
      negatively impacted if patients are convinced that new treatments are better even
      when there are no objective data. Although clinical trials in surgery often are
      challenging to develop and complete, there is an ethical and social
      responsibility for surgeons to participate in clinical trials so that data can be
      gathered to determine what treatments are safe and effective. 

PMID- 23975309
TI  - How genomics, research, ethics and advances translate into improved care for
      breast surgery patients.

PMID- 23975310
TI  - Management of locoregional and systemic recurrence of breast cancer: to stage or
      not to stage and how.
AB  - The surveillance of breast cancer patients after potentially curative treatment
      may result in the identification of locoregional or distant recurrence. While
      many patients expect frequent imaging studies to monitor for recurrence, there
      are no data supporting aggressive imaging surveillance beyond mammography.
      However, when recurrent disease is suspected, it is appropriate to undertake re
      staging to develop a rational management plan. The rationale and methods for
      appropriate surveillance and re-staging are discussed. 

PMID- 23975311
TI  - Interventional ductoscopy for pathological nipple discharge.
AB  - BACKGROUND: Despite the low likelihood of malignancy, it is recommended that
      patients who have pathologic nipple discharge (PND) undergo duct excision.
      Intraductal papilloma is well-known most frequent cause of PND. Our goal is to
      determine whether the ductoscopic retrieval of a solitary papilloma is feasible
      and/or therapeutic for patients with PND. The accompanying video demonstrates
      this interventional ductoscopic approach. METHODS: Consented patients who had
      been diagnosed with PND were recruited to have ductoscopic exploration. Patients
      with palpable masses and suspicion of malignancy on ultrasound or mammography
      were excluded. Under local anesthesia, ductoscopy was performed using LaDuScope-T
      flex with an outer diameter of 1.1 mm, which allows extraction of a single
      papilloma with a microbasket (380 MUm) via a working channel. Patients with
      sessile single papilloma or failure on ductoscopic extraction underwent
      ductoscopically guided microductectomy. Success was determined by recurrence of
      PND and by standard radiological examinations. RESULTS: Three patients presented
      in the video had negative cytology and normal conventional diagnostic imaging.
      Two patients diagnosed with a nonsessile single papilloma underwent successful
      ductoscopic extraction. The interventional examination times of those patients
      were 30 and 35 min. Patient who had a sessile papilloma underwent ductoscopically
      guided microductectomy. These patients had no recurrence of discharge or
      suspicious of malignancy after 5 years follow-up. CONCLUSIONS: Interventional
      ductoscopy provides an incisionless therapeutic option for patients diagnosed
      with a papillary nonsessile benign lesion that causes PND.

PMID- 23975312
TI  - American Society of Breast Surgeons presidential address: treatment by chance.

PMID- 23975313
TI  - Incidence and consequence of close margins in patients with ductal carcinoma-in
      situ treated with mastectomy: is further therapy warranted?
AB  - BACKGROUND: The impact of close margins in patients with ductal carcinoma-in situ
      (DCIS) treated with mastectomy is unclear; however, this finding may lead to a
      recommendation for postmastectomy radiotherapy (PMRT). We sought to determine the
      incidence and consequences of close margins in patients with DCIS treated with
      mastectomy. METHODS: The records of 810 patients with DCIS treated with
      mastectomy from 1996 through 2009 were reviewed. Clinical and pathologic factors
      were analyzed with respect to final margin status. Median follow-up was 6.3
      years. RESULTS: Overall, 94 patients (11.7 %) had close margins (positive, n = 5;
      negative but <=1 mm, n = 54; 1.1-2.9 mm, n = 35). Independent risk factors for
      close margins included multicentricity, pathologic lesion size >=1.5 cm, and
      necrosis, but not age, use of skin-sparing mastectomy, or immediate
      reconstruction (p > 0.05). Seven patients received PMRT, and none had a
      locoregional recurrence (LRR). Among the remaining 803 patients, the 10-year LRR
      rate was 1 % (5.0 % for margins <=1 mm, 3.6 % for margins 1.1-2.9 mm, and 0.7 %
      for margins >=3 mm [p < 0.001]). The 10-year rate of contralateral breast cancer
      was 6.4 %. On multivariate analysis, close margins was the only independent
      predictor of LRR (p = 0.005). CONCLUSIONS: Close margins occur in a minority of
      patients undergoing mastectomy for DCIS and is the only independent risk factor
      for LRR. As the LRR rate in patients with close margins is low and less than the
      rate of contralateral breast cancer, PMRT is not warranted except for patients
      with multiple close/positive margins that cannot be surgically excised.

PMID- 23975314
TI  - Axillary dissection can be avoided in the majority of clinically node-negative
      patients undergoing breast-conserving therapy.
AB  - BACKGROUND: The extent to which ACOSOG Z0011 findings are applicable to patients
      undergoing breast-conserving therapy (BCT) is uncertain. We prospectively
      assessed how often axillary dissection (ALND) was avoided in an unselected,
      consecutive patient cohort meeting Z0011 eligibility criteria and whether
      subgroups requiring ALND could be identified preoperatively. METHODS: Patients
      with cT1,2cN0 breast cancer undergoing BCT were managed without ALND for
      metastases in <3 sentinel nodes (SNs) and no gross extracapsular extension (ECE).
      Patients with and without indications for ALND were compared using Fisher's exact
      and Wilcoxon rank sum tests. RESULTS: From August 2010 to November 2012, 2,157
      invasive cancer patients had BCT. A total of 380 had histologic nodal metastasis;
      93 did not meet Z0011 criteria. Of 287 with >=1 H&E-positive SN (209
      macrometastases), 242 (84 %) had indications for SN only. ALND was indicated in
      45 for >=3 positive SNs (n = 29) or ECE (n = 16). The median number of SNs
      removed in the SN group was 3 versus 5 in the ALND group (p < 0.0001). Age,
      hormone receptor and HER2 status, and grade did not differ between groups; tumors
      were larger in the ALND group (p < 0.0001). Of ALND patients, 72 % had additional
      positive nodes (median = 1; range 1-19). No axillary recurrences have occurred
      (median follow-up, 13 months). CONCLUSIONS: ALND was avoided in 84 % of a
      consecutive series of patients having BCT, suggesting that most patients meeting
      ACOSOG Z0011 eligibility have a low axillary tumor burden. Age, ER, and HER2
      status were not predictive of ALND, and the criteria used for ALND (>=3 SNs, ECE)
      reliably identified patients at high risk for residual axillary disease.

PMID- 23975315
TI  - Axillary dissection can be avoided in the majority of clinically node-negative
      patients undergoing breast-conserving therapy, by Dengel et al.

PMID- 23975316
TI  - Comparison of prognostic scores for patients with colorectal cancer peritoneal
      metastases treated with cytoreductive surgery and hyperthermic intraperitoneal
      chemotherapy.
AB  - BACKGROUND: There are three prognostic scores for the cytoreductive surgery (CRS)
      and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment of colorectal
      cancer peritoneal metastases: the newly introduced COREP (colorectal peritoneal)
      score, the peritoneal surface disease severity score (PSDS), and the prognostic
      score (PS). The aim was to determine which prognostic score had the best
      prognostic value. METHODS: Between 2006 and 2010, a total of 77 patients with
      peritoneal metastases from colorectal cancer underwent CRS/HIPEC treatment. The
      COREP, PSDS, and PS scores were successfully applied to 56 patients (73 %) having
      sufficient data. The end points were prediction of open-and-close cases (n = 9),
      R1 resections (n = 41), and survival of <12 months (n = 18). Area under the
      receiver operating characteristic curves (accuracy) was compared. Subgroup
      analysis was performed on patients not previously used for the development of the
      COREP score (n = 24). Multivariable logistic regressions of the three end points
      were performed as well as Cox regression for overall survival. Furthermore, COREP
      and peritoneal cancer index were compared. RESULTS: For open-and-close case
      prediction, accuracy for the whole group (n = 56) and subgroup (n = 24) was 87
      and 88 %, respectively for COREP; 66 and 77 % for PSDS; and 68 and 78 % for PS.
      For R1 resection prediction, accuracy was 81 and 81 %, 76 and 78 %, and 75 and 77
      %, respectively. For prediction of survival of <12 months, accuracy was 83 and
      84, 54 and 67 %, and 55 and 56 %, respectively. The COREP score was the only
      independent prognostic factor in all four multivariable analyses. A COREP score
      of >=6 identified patients with poor survival more accurately than a PCI of >20.
      CONCLUSIONS: The COREP score predicted open-and-close cases, R1 resections, and
      poor survival better than PSDS and PS. COREP better identifies patients with poor
      survival than intraoperative PCI.

PMID- 23975317
TI  - Prevalence of BRCA mutations among women with triple-negative breast cancer
      (TNBC) in a genetic counseling cohort.
AB  - BACKGROUND: Revised NCCN guidelines recommend that women <=60 years with triple
      negative breast cancer (TNBC) be referred for consideration of genetic
      counseling. Small, homogeneous samples have limited evaluation of BRCA mutation
      prevalence among different ethnicities affected by TNBC subtype. We sought to
      determine whether the prevalence of BRCA mutations within a TNBC cohort differs
      by demographic factors. METHODS: We performed a retrospective review of patients
      with TNBC referred for genetic counseling at two academic Hereditary Cancer
      Clinics between 2000 and 2012. Demographic data were collected, including age at
      diagnosis and race/ethnicity. Race was categorized as African American (AA),
      Ashkenazi Jewish (AJ), Asian, Caucasian, Hispanic, or other. Primary outcome was
      BRCA mutation status, analyzed by race/ethnicity and age at diagnosis. RESULTS: A
      total of 469 patients with TNBC who underwent testing for BRCA genetic mutations
      were identified, of which 450 patients had evaluable BRCA testing results; 139
      (30.8 %) had confirmed BRCA1 (n = 106) or BRCA2 (n = 32) mutations. BRCA mutation
      prevalence differed by ethnicity and race: AA (20.4 %), AJ (50 %), Asian (28.5
      %), Caucasian (33.3 %), and Hispanic (20 %). The prevalence of genetic mutations
      also differed by age at diagnosis: <40 years (43.8 %), 40-49 years (27.4 %), 50
      59 years (25.3 %), 60-69 years (12.5 %), and >70 years (16.6 %). CONCLUSIONS: The
      prevalence of genetic mutations among women with TNBC referred for genetic
      counseling is high and differs significantly by ethnicity/race and age. This data
      helps to refine mutation risk estimates among women with TNBC, allowing for more
      personalized genetic counseling potentially aiding in improved patient decision
      making.

PMID- 23975318
TI  - Should re-excision lumpectomy rates be a quality measure in breast-conserving
      surgery?

PMID- 23975319
TI  - Salvage gastrectomy after intravenous and intraperitoneal paclitaxel (PTX)
      administration with oral S-1 for peritoneal dissemination of advanced gastric
      cancer with malignant ascites.
AB  - BACKGROUND: Peritoneal metastasis of gastric cancer has extremely poor clinical
      outcomes. Recently, we developed a combination chemotherapy that used
      intraperitoneal (IP) paclitaxel (PTX) and produced excellent antitumor effects
      against peritoneal lesions. However, no information is available about the
      benefit of gastrectomy in cases with malignant ascites. METHODS: A total of 64
      patients with severe peritoneal metastasis and ascites received IP PTX at 20
      mg/m(2) via implanted subcutaneous peritoneal access ports as well as intravenous
      (IV) PTX at 50 mg/m(2) on days 1 and 8. S-1 was administered at 80 mg/m(2) day
      for 14 consecutive days, followed by 7 days of rest. In all patients,
      investigative laparoscopy was performed around the combination chemotherapy, and
      gastrectomy was performed on patients who showed apparent shrinkage of their
      peritoneal nodules as well as negative peritoneal cytology at the second
      laparoscopy. RESULTS: Gastrectomy was performed in 34 patients. The median course
      of chemotherapy before surgery was 5 courses (range 2-16). R0 operation was
      achieved in 22 patients (65%), and grade 2 and 3 histological responses were
      obtained in 7 (21%) and 1 (3%) patient(s), respectively. The median survival time
      and 1-year overall survival of the gastrectomized patients were 26.4 months and
      82%, and those of the 30 patients who did not receive gastrectomy were 12.1
      months and 26%, respectively. Morbidity was minimal, and there was no mortality.
      CONCLUSIONS: Salvage gastrectomy after chemotherapy of S-1 with IV and IP PTX is
      promising, even for patients with highly advanced gastric cancer and severe
      peritoneal metastasis and malignant ascites.

PMID- 23975320
TI  - Human acellular dermis seeded with autologous fibroblasts enhances bronchial
      anastomotic healing in an irradiated rodent sleeve resection model.
AB  - BACKGROUND: The combination of neoadjuvant radiochemotherapy and parenchyma
      preserving sleeve resection for lung cancer remains controversial because of
      potentially increased rate of anastomotic breakdown. We analyzed the effects of
      applying a decellularized human dermis transplant seeded with autologous
      fibroblasts in a rodent sleeve resection model with neoadjuvant radiotherapy.
      MATERIALS AND METHODS: A total of 64 male Fisher rats underwent a transsection
      and surgical anastomosis of the left main bronchus and were randomized to receive
      plus/minus radiation treatment and plus/minus augmentation of the anastomosis
      with a fibroblast-seeded dermis transplant (2 * 2 factorial design). A MUCT scan
      was performed at postoperative days 7 and 14, and the animals were sacrificed on
      day 14. Anastomotic bursting pressure and hydroxyproline concentration were
      measured. RESULTS: In the irradiated groups, the anastomotic bursting pressure
      was significantly higher in the augmented group at day 7 (100.9 +/- 18.3 vs 141.3
      +/- 18.0 kPa, p = 0.0005) but not at day 14. Hydroxyproline levels showed a
      similar pattern in the irradiated group with significant differences at day 7 (7
      days postoperative 158 +/- 11.6 vs 198.2 +/- 10.9 nmol/mg, p < 0.0001) but not at
      day 14 postoperatively. CONCLUSIONS: Augmentation of a bronchial anastomosis by a
      dermal matrix, seeded with autologous, viable fibroblasts improves early wound
      breaking strength. Fibroblast-enhanced dermal matrices provide a new and easily
      usable tool to prevent early anastomotic leakage after neoadjuvant chemoradiation
      in locally advanced lung cancer.

PMID- 23975321
TI  - Prognostic factors in elderly osteosarcoma patients: a multi-institutional
      retrospective study of 86 cases.
AB  - BACKGROUND: The occurrence of osteosarcoma in elderly patients has recently been
      increasing, and the outcome is poor. This multi-institutional retrospective study
      was conducted to investigate clinical features and prognostic factors in patients
      older than 40 years with osteosarcoma. METHODS: Patients with conventional high
      grade osteosarcoma older than 40 years were recruited to this study. Secondary
      osteosarcoma arising from Paget's disease or irradiated bones was excluded.
      Information on tumor- and treatment-related factors was collected and
      statistically analyzed. The median follow-up was 57 months (range 8-244 months)
      for all surviving patients. RESULTS: A total of 86 patients were enrolled in this
      study. The median age at diagnosis was 61 years. Surgery and chemotherapy were
      conducted in 73 and 63 % of all patients, respectively. The 5-year overall and
      event-free survival rates were 38.8 and 34.0 %, respectively. Tumor site
      (extremity 57.9 %; axial 19.0 %; p < 0.0001), metastasis at diagnosis (yes 12.2
      %; no 48.3 %; p < 0.0091), and definitive surgery (yes 56.2 %; no 10.6 %; p <
      0.0001) were associated with overall survival. Although patients without
      metastasis who received definitive surgery were regarded as good candidates for
      chemotherapy, the addition of chemotherapy did not have any impact on the outcome
      (yes 63.4 %; no 65.2 %; p = 0.511). CONCLUSIONS: The present study revealed the
      distinct clinical features, such as the high incidence of truncal tumors or
      metastasis at diagnosis, in patients older than 40 years with osteosarcoma.
      Additionally, prognostic factor analyses revealed that tumor site, metastasis at
      diagnosis, definitive surgery, and surgical margins were significant prognostic
      factors, whereas chemotherapy did not influence survival.

PMID- 23975322
TI  - STMN-1 gene: a predictor of survival in stage iia esophageal squamous cell
      carcinoma after Ivor-Lewis esophagectomy?
AB  - BACKGROUND: Prognosis of esophageal squamous cell carcinoma (ESCC) is stage
      specific; however, some patients with the same stage have different survival
      outcomes. Clinically, it is significant to explore the biological marker to
      predict patient's outcome. We investigated the association between the stathmin1
      gene (STMN-1) expression and the prognosis of patients who underwent Ivor-Lewis
      esophagectomy. METHODS: A total of 162 patients who suffered from midthoracic
      stage IIA ESCC and completely resected with Ivor-Lewis esophagectomy were studied
      for STMN-1 expression by qRT-PCR in fresh-frozen tissue and validated by
      immunohistochemistry in matched formalin fixed-paraffin embedded tissue samples.
      STMN-1 level was evaluated as a prognostic factor in ESCC. SPSS 21.0 software was
      used to analyze the relationship between STMN-1 expression and
      clinicopathological characteristics and survival probability. RESULTS: The
      overall 3- and 5-year survival was 72.20 and 42.00 % respectively. Ninety-four
      patients (58.02 %) experienced disease recurrence with a disease-free interval of
      21.50 +/- 1.20 months. qRT-PCR result showed that STMN-1 mRNA level in patients
      who were alive at the end of follow-up was lower compared with patients who died
      during the follow-up period (p < 0.05). Immunohistochemical results showed that
      94 patients had STMN-1 protein overexpression (58.02 %), patient with STMN-1
      overexpression had worse survival compared with patients who had low STMN-1
      expression (p = 0.00). Cox regression analysis revealed that STMN-1 protein
      expression and T classification are independent prognostic factors. CONCLUSIONS:
      Even localized ESCC are potential to relapse with poor prognosis. This study
      demonstrates that STMN-1 level is an independent prognostic factor after Ivor
      Lewis esophagectomy. In addition, assessment of STMN-1 level could improve
      stratification of stage IIA ESCC patients.

PMID- 23975323
TI  - Quality improvement in colorectal cancer in local health integration network 4
      (LHIN 4) project (QICC-L4): integrated knowledge translation in a large
      geographic region.
AB  - BACKGROUND: Stakeholders suggest that integrating end users into the planning and
      execution of quality improvement interventions may more effectively close quality
      gaps. We tested if such an approach could improve the quality of colorectal
      cancer surgery in a large geographic region (i.e., LHIN4) in Ontario, Canada.
      METHODS: All LHIN4 surgeons who provide colorectal cancer surgery were invited to
      an October 2006 inaugural QICC-L4 workshop and subsequent workshops in 2008,
      2010, and 2012. At workshops, surgeons selected clinically relevant quality
      markers for targeted improvement and interventions to achieve improvements.
      Selected markers included rates of colon and rectal radiology imaging, rate of
      pathology reporting of rectal radial margin distance, and rate of positive rectal
      radial margins. To date, implemented interventions have included audit and
      feedback, tailoring interviews to identify barriers and facilitators to optimal
      quality, and preoperative internet-based patient reviews. Hospital and regional
      cancer centre charts provide audit data for annual feedback reports to surgeons.
      RESULTS: Participating surgeons at workshops and surgeon participants in
      preoperative reviews treated approximately 70 % of all LHIN4 patients undergoing
      colorectal surgery. For years 2006-2012, the rate of radiology imaging for colon
      and rectal cases increased from 70 to 91 % and from 71 to 91 %, respectively. For
      rectal cases, the rate of reporting radial margins increased (55-93 %), and the
      rate of positive radial margins decreased (14-6 %). CONCLUSIONS: Initiation of
      the integrated knowledge translation QICC-L4 project in a large geographic region
      was associated with marked improvements in relevant colorectal cancer surgery
      quality markers.

PMID- 23975324
TI  - Mediterranean diet and glycaemic load in relation to incidence of type 2
      diabetes: results from the Greek cohort of the population-based European
      Prospective Investigation into Cancer and Nutrition (EPIC).
AB  - AIMS/HYPOTHESIS: The role of diet in the prevention of diabetes remains
      uncertain. The aim of this study was to investigate two different dietary
      aspects, i.e. adherence to the Mediterranean diet and glycaemic load (GL), in
      relation to diabetes occurrence. METHODS: We analysed data from the Greek cohort
      of the population-based European Prospective Investigation into Cancer and
      Nutrition (EPIC). From a total of 22,295 participants, actively followed for a
      median of 11.34 years, 2,330 cases of incident type 2 diabetes were recorded. All
      participants completed a validated, interviewer-administered semi-quantitative
      food frequency questionnaire at enrolment. From this information, we calculated a
      ten point Mediterranean diet score (MDS), reflecting adherence to the traditional
      Mediterranean diet, as well as the dietary GL. We estimated HRs and the
      corresponding 95% CIs of diabetes using Cox proportional hazards regression
      models adjusted for potential confounders. RESULTS: A higher MDS was inversely
      associated with diabetes risk (HR 0.88 [95% CI 0.78, 0.99] for MDS >= 6 vs MDS <=
      3). GL was positively associated with diabetes (HR 1.21 [95% CI 1.05, 1.40] for
      the highest vs the lowest GL quartile). A significant protection of about 20% was
      found for a diet with a high MDS and a low GL. CONCLUSIONS/INTERPRETATION: A low
      GL diet that also adequately adheres to the principles of the traditional
      Mediterranean diet may reduce the incidence of type 2 diabetes.

PMID- 23975325
TI  - Does metformin modify the effect on glycaemic control of aerobic exercise,
      resistance exercise or both?
AB  - AIMS/HYPOTHESIS: Some previous studies suggested that metformin might attenuate
      the effects of exercise on glycaemia or fitness. We therefore examined whether
      metformin use influenced changes in glycaemic control, fitness, body weight or
      waist circumference resulting from aerobic and/or resistance training in people
      with type 2 diabetes participating in an exercise intervention trial. METHODS:
      After a 4 week run-in period, participants from the Diabetes Aerobic and
      Resistance Exercise (DARE) trial were randomly assigned to 22 weeks of aerobic
      training alone, resistance training alone, combined aerobic and resistance
      exercise training or a waiting-list control group. Of the 251 randomised, 143
      participants reported using metformin throughout the entire study period and 82
      reported not using metformin at all. RESULTS: Compared with control, aerobic
      training led to a significant reduction in HbA1c in the metformin users (-0.57%,
      95% CI -1.05, -0.10; -6.3 mmol/mol, 95% CI -11.5, -1.1) but not in the non
      metformin users (-0.17, 95% CI -0.78, 0.43; -1.9 mmol/mol, 95% CI -8.5, 4.7).
      However, there were no significant differences in the changes in HbA1c (or
      fasting glucose) between metformin users and non-users in any of the exercise
      groups compared with control (p> 0.32 for all metformin by group by time
      interactions). Similarly, metformin did not affect changes in indicators of
      aerobic fitness, strength and body weight or waist circumference (p >= 0.15 for
      all metformin by group by time interactions). CONCLUSIONS/INTERPRETATION:
      Contrary to our hypothesis and to previous short-term studies, metformin did not
      significantly attenuate the benefits of exercise on glycaemic control or fitness.

PMID- 23975326
TI  - The effect of submicron fat droplets in a drink on satiety, food intake, and
      cholecystokinin in healthy volunteers.
AB  - PURPOSE: Small fat droplets infused into the gut reduce food intake and hunger
      more than bigger ones, at levels as low as 6 g, and these effects are
      hypothesized to occur via satiety hormones such as cholecystokinin. It is,
      however, unknown whether the effect of droplet size would persist after oral
      consumption. It is also unknown whether an even smaller droplet size can affect
      hunger and food intake and at what minimum amount of fat. Therefore, the aim of
      the study was to test the effect of very fine fat droplets on satiety and food
      intake in two different quantities. METHODS: In a balanced-order 4-way crossover
      design, 24 volunteers consumed a fat-free meal replacement drink with either 5 or
      9 g oil (rapeseed) and either 3 or 0.1 MUm droplet size. Appetite scores and
      plasma cholecystokinin levels (in n = 12 subset) were measured for 180 min, when
      food intake was assessed during an ad libitum meal. Data were analyzed by ANCOVA,
      followed by Dunnett's test and paired t test. The behavior of the emulsions was
      also characterized in a simulated gastrointestinal model. RESULTS: Despite faster
      in vitro lipolysis of the smallest droplets, neither droplet size nor fat amount
      affected satiety or food intake. From t = 45-150 min, cholecystokinin response
      was 50% higher (P < 0.05) after the 0.1 versus 3 MUm, but only with 9 g fat.
      CONCLUSION: When this particular fat at these amounts is delivered in a meal
      replacement drink, droplet size does not influence appetite or food intake. This
      effect is independent of the amount of fat or plasma cholecystokinin changes.

PMID- 23975328
TI  - The subjective experience of using Ignatian meditation by male and female South
      African university students: an exploratory study.
AB  - This study is set out to examine the subjective experience of using the Ignatian
      method of meditation to reflect on and pray through Ruth 2. A group of male and
      female Theology students from the University of KwaZulu-Natal were invited to
      reflect upon/pray through Ruth 2 using Ignatian meditation. Following this
      exercise, participants were invited to participate in a focus group in which they
      shared their experience of this exercise, focusing particularly on some of the
      gendered aspects of the experience. The transcribed focus group material was
      subjected to a critical thematic analysis, in order to identify which core
      aspects of the experience of using this method of meditation and reflection were
      responsible for the reported subjective experiences. The analysis also included a
      comparison of the experience for men and women participating in this exercise,
      and the differential effect of various aspects of the exercise on men and women. 

PMID- 23975327
TI  - Preventing staple-line leak in sleeve gastrectomy: reinforcement with bovine
      pericardium vs. oversewing.
AB  - One of the most serious, potentially life-threatening complications of
      laparoscopic sleeve gastrectomy (LSG) is staple-line leakage. Oversewing the LSG
      staple line vs buttressing it with bovine pericardial strips (BPS) to reduce
      perioperative bleeding and postoperative gastric leak was evaluated. From 2006
      through 2011, 160 patients underwent LSG with suturing as the only staple-line
      reinforcement (Group A). From March 2010 through August 2012, 84 LSG patients had
      BPS incorporated into their last two stapler firings (Group B). Staple lines were
      evaluated perioperatively for bleeding, and patients were monitored for
      indications of staple-line leaks (peritonitis, abnormal output from the drain).
      In preoperative Group A and B, there were 117 (73.1%) vs. 56 (66.7%) females;
      mean age, 35.2 years (18.0-68.0) vs. 33.8 years (15.0-64.0); mean body mass index
      (BMI, kilograms per square meter), 42.5 (27.0-76.0) vs. 42.0 (30.0-58.0). Three
      months after surgery, mean BMI for Group A was 37.3 (-5.9); Group B, 35.2 (-7.3);
      at 6 months, 32.7 (-10.8) and 31.5 (-11.3; p < 0.001). Although there was no
      significant difference in perioperative blood loss, oversewn staple lines in
      Group A often required electrocautery to stanch bleeding; this was not required
      for Group B. In Group A, 15 patients (9.4%) developed complications; in Group B,
      five (6.0%; p = 0.46). Gastric fistula, verified by barium swallow, occurred in
      eight Group A patients (5.0%); in Group B, one (1.2%; p = 0.17). Relative to
      oversewing, staple-line buttressing with bovine pericardium was readily
      accomplished, safe, and associated with a lower staple-line leak rate.

PMID- 23975329
TI  - A phase I/II study of carfilzomib 2-10-min infusion in patients with advanced
      solid tumors.
AB  - PURPOSE: Tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor
      activity of carfilzomib, a selective proteasome inhibitor, administered twice
      weekly by 2-10-min intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 in 28
      day cycles, were assessed in patients with advanced solid tumors in this phase
      I/II study. METHODS: Adult patients with solid tumors progressing after >=1 prior
      therapies were enrolled. The dose was 20 mg/m(2) in week 1 of cycle 1 and 20, 27,
      or 36 mg/m(2) thereafter. The maximum tolerated dose or protocol-defined maximum
      planned dose (MPD) identified during dose escalation was administered to an
      expansion cohort and to patients with small cell lung, non-small cell lung,
      ovarian, and renal cancer in phase II tumor-specific cohorts. RESULTS: Fourteen
      patients received carfilzomib during dose escalation. The single dose-limiting
      toxicity at 20/36 mg/m(2) was grade 3 fatigue, establishing the MPD as the
      expansion and phase II dose. Sixty-five additional patients received carfilzomib
      at the MPD. Adverse events included fatigue, nausea, anorexia, and dyspnea.
      Carfilzomib PK was dose proportional with a half-life <1 h. All doses resulted in
      at least 80 % proteasome inhibition in blood. Partial responses occurred in two
      patients in phase I, with 21.5 % stable disease after four cycles in evaluable
      patients in the expansion and phase II cohorts. CONCLUSION: Carfilzomib 20/36
      mg/m(2) was well tolerated when administered twice weekly by 2-10-min IV
      infusion. At this dose and infusion rate, carfilzomib inhibited the proteasome in
      blood but demonstrated limited antitumor activity in patients with advanced solid
      tumors.

PMID- 23975332
TI  - Impact of cooking and digestion, in vitro, on the antioxidant capacity and anti
      inflammatory activity of cinnamon, clove and nutmeg.
AB  - The impact of cooking and digestion on the antioxidant capacity (AC), estimated
      total phenolic content (TPC) and anti-inflammatory activity (AA) of culinary
      spices was determined to investigate their significance as dietary contributors
      to these properties. Extracts of uncooked (U), cooked (C) and cooked and
      digested, in vitro, (D) cinnamon, clove and nutmeg were prepared and the TPC, AC
      and AA, specifically the inhibition of cyclo-oxygenase 2 (COX-2) and the amount
      of prostaglandin (PG) synthesized, were determined. Compared to their uncooked
      (U) counterparts, the following changes were statistically significant: the AC
      and TPC for (C) clove, and the TPC for (D) clove decreased, the TPC for (D) clove
      increased, the TPC for (C) nutmeg increased, and the AC and TPC for (D) nutmeg
      increased, and the TPC for (C) and (D) nutmeg increased. All the spices achieved
      near 100 % inhibition of COX-2 which was associated with the inhibition of the
      amount of PG synthesized. Based on estimated levels of ingestion, cinnamon
      possesses a much higher AC than clove and nutmeg because it is typically used in
      larger quantities. For AA, (U, C and D) cinnamon and clove maintain near 100 %
      inhibition of COX-2 but only the inhibitory potential of (D) nutmeg could be
      ascertained (70 %). Cooking and digestion alter the TPC and AC of these spices
      although the changes are not consistent between spices or across treatments. In
      contrast to AC, significant AA is likely to be present in these spices at amounts
      used in cooking. 

PMID- 23975330
TI  - Blood pressure circadian pattern and physical exercise assessment by
      accelerometer and 7-day physical activity recall scale.
AB  - BACKGROUND: The relationship between regular physical activity, measured
      objectively and by self-report, and the circadian pattern of 24-hour ambulatory
      arterial blood pressure (BP) has not been clarified. METHODS: We performed a
      cross-sectional study in a cohort of healthy patients. We included 1,345 patients
      from the EVIDENT study (mean age 55 +/- 14 years; 59.3% women). Physical activity
      was assessed using the 7-day physical activity recall (PAR) questionnaire
      (metabolic equivalents (MET)/hour/week) and the Actigraph GT3X accelerometer
      (counts/minute) for 7 days; ambulatory arterial BP was measured with a radial
      tonometer (B-pro device). RESULTS: The dipper-pattern patients showed a higher
      level of activity than nondipper patients, as assessed by accelerometer and 7-day
      PAR. Physical activity measures correlated positively with the percent drop in
      systolic BP (SBP; rho = 0.19 to 0.11; P < 0.01) and negatively with the systolic
      and diastolic sleep to wake ratios (rho = -0.10 to -0.18; P < 0.01) and heart
      rate (rho = -0.13; P < 0.01). In logistic regression, considering the circadian
      pattern (1, dipper; 0, nondipper) as the dependent variable, the odds ratio of
      the third tertile of counts/minute was 1.79 (95% confidence interval [CI], 1.35
      2.38; P < 0.01) and of MET/hour/week was 1.33 (95% CI, 1.01-1.75; P = 0.04) after
      adjustment for confounding variables. CONCLUSIONS: Physical activity, as
      evaluated by both the accelerometer and the 7-day PAR, was associated with a more
      marked nocturnal BP dip and, accordingly, a lower SBP and diastolic BP sleep to
      wake ratio. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov Identifier:
      NCT01083082.

PMID- 23975331
TI  - Causes of medication administration errors in hospitals: a systematic review of
      quantitative and qualitative evidence.
AB  - BACKGROUND: Underlying systems factors have been seen to be crucial contributors
      to the occurrence of medication errors. By understanding the causes of these
      errors, the most appropriate interventions can be designed and implemented to
      minimise their occurrence. OBJECTIVE: This study aimed to systematically review
      and appraise empirical evidence relating to the causes of medication
      administration errors (MAEs) in hospital settings. DATA SOURCES: Nine electronic
      databases (MEDLINE, EMBASE, International Pharmaceutical Abstracts, ASSIA,
      PsycINFO, British Nursing Index, CINAHL, Health Management Information Consortium
      and Social Science Citations Index) were searched between 1985 and May 2013.
      STUDY SELECTION: Inclusion and exclusion criteria were applied to identify
      eligible publications through title analysis followed by abstract and then full
      text examination. English language publications reporting empirical data on
      causes of MAEs were included. Reference lists of included articles and relevant
      review papers were hand searched for additional studies. Studies were excluded if
      they did not report data on specific MAEs, used accounts from individuals not
      directly involved in the MAE concerned or were presented as conference abstracts
      with insufficient detail. DATA APPRAISAL AND SYNTHESIS METHODS: A total of 54
      unique studies were included. Causes of MAEs were categorised according to
      Reason's model of accident causation. Studies were assessed to determine
      relevance to the research question and how likely the results were to reflect the
      potential underlying causes of MAEs based on the method(s) used. RESULTS: Slips
      and lapses were the most commonly reported unsafe acts, followed by knowledge
      based mistakes and deliberate violations. Error-provoking conditions influencing
      administration errors included inadequate written communication (prescriptions,
      documentation, transcription), problems with medicines supply and storage
      (pharmacy dispensing errors and ward stock management), high perceived workload,
      problems with ward-based equipment (access, functionality), patient factors
      (availability, acuity), staff health status (fatigue, stress) and
      interruptions/distractions during drug administration. Few studies sought to
      determine the causes of intravenous MAEs. A number of latent pathway conditions
      were less well explored, including local working culture and high-level
      managerial decisions. Causes were often described superficially; this may be
      related to the use of quantitative surveys and observation methods in many
      studies, limited use of established error causation frameworks to analyse data
      and a predominant focus on issues other than the causes of MAEs among studies.
      LIMITATIONS: As only English language publications were included, some relevant
      studies may have been missed. CONCLUSIONS: Limited evidence from studies included
      in this systematic review suggests that MAEs are influenced by multiple systems
      factors, but if and how these arise and interconnect to lead to errors remains to
      be fully determined. Further research with a theoretical focus is needed to
      investigate the MAE causation pathway, with an emphasis on ensuring interventions
      designed to minimise MAEs target recognised underlying causes of errors to
      maximise their impact.

PMID- 23975333
TI  - Accelerated endothelialization with a polymer-free sirolimus-eluting antibody
      coated stent.
AB  - Drug-eluting stents have shown an impressive reduction of in-stent restenosis for
      many years. However, stent thrombosis due to incomplete/late endothelialization
      has raised major safety concerns. To overcome these problems, we developed for
      the first time a polymer-free sirolimus-eluting antibody-coated stent (PFSEACS)
      by combining polymer free and endothelial progenitor cell-capture pro-healing
      approaches. In the first phase, the stents were prepared by loading sirolimus on
      the porous outer stent surface and directly fixing the anti-CD34 antibodies
      without any medium carriers on the blood contacting surface. The dose and elution
      of sirolimus, the amount and stability of anti-CD34 antibody immobilization, and
      the rate of CD34+ cell capture were evaluated. In the second phase, the stents
      were validated in an animal model of coronary arteries in pigs. The stent was
      observed to start collecting endothelial progenitor cells ~2 h after stent
      implantation and exhibited greatly enhanced endothelialization while maintaining
      an excellent anti-restenosis activity comparable to the polymer-free sirolimus
      eluting stents. Overall, both in vitro and in vivo evaluations indicated that
      novel PFSEACSs exhibited facilitated endothelialization with excellent anti
      restenosis activity and thus should merit further clinical studies.

PMID- 23975335
TI  - Periprosthetic patellar fractures.
AB  - Periprosthetic patellar fractures represent a spectrum of injuries to a patient
      with a total knee arthroplasty. They range in severity from an inconsequential
      injury, which does not compromise function, to a severely debilitating injury
      that may require advanced reconstructive measures. This article will outline the
      epidemiology and risk factors associated with periprosthetic patellar fractures.
      Treatment options as they relate to injury mechanism, fracture severity, patellar
      component stability, and remaining bone stock will also be discussed. Finally, a
      review of the current literature regarding the results of treatment will be
      presented. 

PMID- 23975334
TI  - Poly(2-oxazoline)s as materials for biomedical applications.
AB  - The conjunction of polymers and medicine enables the development of new materials
      that display novel features, opening new ways to administrate drugs, design
      implants and biosensors, to deliver pharmaceuticals impacting cancer treatment,
      regenerative medicine or gene therapy. Poly(2-oxazoline)s (POx) constitute a
      polymer class with exceptional properties for their use in a plethora of
      different biomedical applications and are proposed as a versatile platform for
      the development of new medicine. Herein, a global vision of POx as a platform for
      novel biomaterials is offered, by highlighting the recent advances and
      breakthroughs in this fascinating field.

PMID- 23975336
TI  - Characterization and modulation of glucose uptake in a human blood-brain barrier
      model.
AB  - The blood-brain barrier (BBB) plays a key role in limiting and regulating glucose
      access to glial and neuronal cells. In this work glucose uptake on a human BBB
      cell model (the hCMEC/D3 cell line) was characterized. The influence of some
      hormones and diet components on glucose uptake was also studied. 3H-2-deoxy-D
      glucose ([3H]-DG) uptake for hCMEC/D3 cells was evaluated in the presence or
      absence of tested compounds. [3H]-DG uptake was sodium- and energy-independent.
      [3H]-DG uptake was regulated by Ca2+ and calmodulin but not by MAPK kinase
      pathways. PKC, PKA and protein tyrosine kinase also seem to be involved in
      glucose uptake modulation. Progesterone and estrone were found to decrease 3H-DG
      uptake. Catechin and epicatechin did not have any effect, but their methylated
      metabolites increased [3H]-DG uptake. Quercetin and myricetin decreased [3H]-DG
      uptake, and glucuronic acid-conjugated quercetin did not have any effect. These
      cells expressed GLUT1, GLUT3 and SGLT1 mRNA.

PMID- 23975337
TI  - Evaluation of voltage-sensitive fluorescence dyes for monitoring neuronal
      activity in the embryonic central nervous system.
AB  - Using an optical imaging technique with voltage-sensitive dyes (VSDs), we
      investigated the functional organization and architecture of the central nervous
      system (CNS) during embryogenesis. In the embryonic nervous system, a merocyanine
      rhodanine dye, NK2761, has proved to be the most useful absorption dye for
      detecting neuronal activity because of its high signal-to-noise ratio (S/N), low
      toxicity and small dye bleaching. In the present study, we evaluated the
      suitability of fluorescence VSDs for optical recording in the embryonic CNS. We
      screened eight styryl (hemicyanine) dyes in isolated brainstem-spinal cord
      preparations from 7-day-old chick embryos. Measurements of voltage-related
      optical signals were made using a multiple-site optical recording system. The
      signal size, S/N, photobleaching, effects of perfusion and recovery of neural
      responses after staining were compared. We also evaluated optical responses with
      various magnifications. Although the S/N was lower than with the absorption dye,
      clear optical responses were detected with several fluorescence dyes, including
      di-2-ANEPEQ, di-4-ANEPPS, di-3-ANEPPDHQ, di-4-AN(F)EPPTEA, di-2-AN(F)EPPTEA and
      di-2-ANEPPTEA. Di-2-ANEPEQ showed the largest S/N, whereas its photobleaching was
      faster and the recovery of neural responses after staining was slower. Di-4
      ANEPPS and di-3-ANEPPDHQ also exhibited a large S/N but required a relatively
      long time for recovery of neural activity. Di-4-AN(F)EPPTEA, di-2-AN(F)EPPTEA and
      di-2-ANEPPTEA showed smaller S/Ns than di-2-ANEPEQ, di-4-ANEPPS and di-3
      ANEPPDHQ; but the recovery of neural responses after staining was faster. This
      study demonstrates the potential utility of these styryl dyes in optical
      monitoring of voltage changes in the embryonic CNS. 

PMID- 23975338
TI  - Response to "What do aquaporin knockout studies tell us about fluid transport in
      epithelia?" Maclaren OJ, Sneyd J, Crampin EJ (2013) J Membr Biol 246:297-305.

PMID- 23975339
TI  - Fibrocytes are involved in inflammation as well as fibrosis in the pathogenesis
      of Crohn's disease.
AB  - BACKGROUND: We previously showed that fibrocytes, a hematopoietic stem cell
      source of fibroblasts/myofibroblasts, infiltrated the colonic mucosa of a murine
      colitis model. AIM: We investigated whether fibrocytes were involved in the
      pathogenesis of Crohn's disease. METHODS: Human surgical intestinal specimens
      were stained with anti-leukocyte-specific protein 1 and anti-collagen type-I
      (ColI) antibodies. Circulating fibrocytes in the human peripheral blood were
      quantified by fluorescence-activated cell sorting with anti-CD45 and anti-ColI
      antibodies. Cultured human fibrocytes were prepared by culturing peripheral
      CD14(+) monocytes. RESULTS: In the specimens of patients with Crohn's disease,
      the fibrocyte/total leukocyte percentage was significantly increased in
      inflammatory lesions (22.2 %, p < 0.01) compared with that in non-affected areas
      of the intestine (2.5 %). Interestingly, the percentage in fibrotic lesions was
      similar (2.2 %, p = 0.87) to that in non-affected areas. The percentages of
      circulating fibrocytes/total leukocytes were significantly higher in patients
      with Crohn's disease than in healthy controls. Both CXC-chemokine receptor 4(+)
      and intercellular adhesion molecule 1(+) fibrocyte numbers were significantly
      increased in Crohn's disease, suggesting that circulating fibrocytes have a
      higher ability to infiltrate injured sites and traffic leukocytes. In cultured
      fibrocytes, lipopolysaccharide treatment remarkably upregulated tumor necrosis
      factor (TNF)-alpha mRNA (17.0 +/- 5.7-fold) and ColI mRNA expression (12.8 +/-
      5.7-fold), indicating that fibrocytes stimulated by bacterial components directly
      augmented inflammation as well as fibrosis. CONCLUSIONS: Fibrocytes are recruited
      early in the inflammatory phase and likely differentiate into
      fibroblasts/myofibroblasts until the fibrosis phase. They may enhance
      inflammation by producing TNF-alpha and can directly augment fibrosis by
      producing ColI.

PMID- 23975340
TI  - Cyclooxygenase-2 promotes hepatocellular apoptosis by interacting with TNF-alpha
      and IL-6 in the pathogenesis of nonalcoholic steatohepatitis in rats.
AB  - BACKGROUND AND PURPOSE: The underlying mechanisms of nonalcoholic steatohepatitis
      (NASH) are poorly understood, and little is known about hepatocellular apoptosis
      in NASH. Cyclooxygenase (COX)-2, the key enzyme in eicosanoid metabolism, is
      highly expressed in NASH. COX-2 can also regulate the release of mediators of
      inflammation, such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6.
      The aim of our study was to evaluate the effects of COX-2 on hepatocellular
      apoptosis and the mechanism of the action in the pathogenesis of NASH in rats.
      METHODS: Sprague-Dawley rats were fed a high-fat diet (HFD) or standard diet for
      8 and 12 weeks. COX-2 and cytokines expression in hepatic tissue and TNF-alpha
      and IL-6 levels in serum were measured at 8 and 12 weeks. Moreover, celecoxib (10
      mg/kg body weight once a day) was administered to rats for 4 weeks to inhibit the
      expression of COX-2. Liver pathology was assessed by hematoxylin and eosin (H&E)
      stain and electron microscopy. Hepatocyte apoptosis was evaluated by TUNEL
      staining. RESULTS: COX-2 messenger RNA and protein were highly expressed in
      livers of HFD rats and were correlated with the severity of steatohepatitis (R =
      0.82, p < 0.01). COX-2 upregulation was preceded by increases in TNF-alpha and IL
      6. The level of hepatocellular apoptosis was significantly higher in HFD rats
      than in the control rats. The hepatocellular apoptosis was suppressed by the
      inhibition of COX-2. CONCLUSIONS: COX-2 may promote hepatocellular apoptosis by
      interacting with TNF-alpha and IL-6 in NASH in rats.

PMID- 23975341
TI  - Predictive factors for early mortality after percutaneous endoscopic and
      radiologically-inserted gastrostomy.
AB  - BACKGROUND: Gastrostomy insertion is of benefit to selected patients, but 30-day
      mortality is as high as 54% in some patient groups. The current study examines
      risk factors associated with 30-day mortality in a cohort of patients who
      underwent percutaneous endoscopic gastrostomy (PEG) or radiologically-inserted
      gastrostomy (RIG) in a district general hospital over a 2.5 year period. METHODS:
      A retrospective review of case notes was performed for all patients who underwent
      a PEG (n=53) or RIG (n=40) insertion in the period January 2009-July 2011.
      PEG/RIG re-insertions were excluded. Demographic, clinical, and biochemical data
      were analysed. Multivariate regression analysis was used to identify risk factors
      for early mortality after gastrostomy insertion. RESULTS: The indications for
      gastrostomy insertion were similar in the PEG and RIG groups and included mainly
      dysphagic stroke, chronic neuromuscular disease and head and neck cancer. The
      patients in the RIG group were older and had a higher incidence of cardiovascular
      co-morbidities. The overall 30-day mortality was 11% in the PEG and 40% in the
      RIG group. The multivariate regression analysis suggested that cardiovascular co
      morbidities and RIG insertion were independent risk factors for early mortality.
      The main cause of death 30 days after gastrostomy insertion was pneumonia, which
      was significantly more common in the RIG group. CONCLUSIONS: Our data suggest
      that PEG should be the procedure of choice when considering gastrostomy insertion
      and RIG should be reserved as a second-line approach for cases in which PEG is
      technically difficult or contraindicated.

PMID- 23975343
TI  - Evaluation of early precut with needle-knife in difficult biliary cannulation
      during ERCP.
AB  - BACKGROUND: There is scarce information on whether performing the precut
      procedure early rather than after several cannulation attempts is associated with
      different success and complication rates. OBJECTIVE: The aim of this
      retrospective study was is to compare the early precut technique with the
      standard one in terms of the results and complications. METHODS: The contemporary
      success rate and postoperative complications in 792 endoscopic retrograde
      cholangiopancreatography cases were frequently observed during the period from
      June 2007 to May 2011, and 56 of these cases were carried out with precut biliary
      sphincterotomy after the standard sphincterotomy had failed. RESULTS: The success
      rate for standard sphincterotomy was 89.8%: 51 out of 56 cases were carried out
      with precut biliary sphincterotomy and succeeded. The total success rate was
      96.3%. The difference was significant (chi2=25.62, p<0.01) compared to the
      success rate of first cannulation, while the difference in complication rates
      between precut and standard sphincterotomy was minor (9.9 vs. 12.5%, p>0.05).
      CONCLUSION: Early precut with a needle-knife in a difficult biliary cannulation
      was safe and effective if performed by experienced endoscopists.

PMID- 23975342
TI  - Melatonin reduces ulcerative colitis-associated local and systemic damage in
      mice: investigation on possible mechanisms.
AB  - BACKGROUND AND AIMS: Ulcerative colitis (UC) is a chronic gastrointestinal
      disorder. Substantial research reveals that melatonin has beneficial effects in
      ulcerative colitis both experimentally and clinically. We have previously
      reported that ulcerative colitis was associated with local and systemic damage in
      mice. The purpose of this study was to reveal the novel targets of melatonin in
      its protective mechanism against ulcerative colitis in mice. We also wished to
      determine whether or not melatonin protected against ulcerative colitis-induced
      systemic damage in mice. METHODS: Ulcerative colitis was induced in mice by use
      of 3% (w/v) dextran sulfate sodium for two cycles. One cycle comprised 7 days of
      DSS-treated water followed by 14 days of normal drinking water. Melatonin was
      administered at doses of 2, 4, or 8 mg/kg bw/day, po throughout. The effect of
      melatonin in mice with UC was evaluated by use of biochemical data, histological
      evaluation, comet and micronucleus assays, immunohistochemistry, and western blot
      analysis. RESULTS: The results indicated that melatonin treatment ameliorated the
      severity of ulcerative colitis by modulating a variety of molecular targets, for
      example nuclear factor kappa B, cyclooxygenase-2, interleukin 17, signal
      transducer and activator of transcription 3, nuclear erythroid 2-related factor
      2, matrix metalloproteinase-9, and connective tissue growth factor. Further,
      ulcerative colitis increased gut permeability, plasma lipopolysaccharide level,
      systemic inflammation, and genotoxicity. Melatonin treatment led to mucosal
      healing and reduced ulcerative colitis-induced elevated gut permeability and
      reduced the plasma LPS level, systemic inflammation, and genotoxicity.
      CONCLUSION: Melatonin ameliorated ulcerative colitis-associated local and
      systemic damage in mice.

PMID- 23975344
TI  - Quantitative classification of HbA1C and blood glucose level for diabetes
      diagnosis using neural networks.
AB  - In this study, artificial neural network structures were used for the
      quantitative classification of Haemoglobin A1C and blood glucose level for
      diabetes diagnosis as a non-invasive measurement technique. The neural network
      structures make inferences from the relationship between the palm perspiration
      and blood data values. For this purpose, feed forward multilayer, Elman, and
      radial basis neural network structures were used. The quartz crystal microbalance
      type and humidity sensors were used for the detection of palm perspiration rates.
      Total 297 volunteer's data is used in this study. Three quarters of the data was
      used to train the neural networks. The remaining data were used as test data. The
      best results for the quantitative classification were obtained from the feed
      forward NN structure for the detection of the glucose and HbA1C level quantities.
      And, the performances of all neural networks for the HbA1C value were better than
      the performances of these neural networks for the glucose level. 

PMID- 23975346
TI  - Increasing the "smoking age": the right thing to do.

PMID- 23975345
TI  - The human cuneate nucleus contains discrete subregions whose neurochemical
      features match those of the relay nuclei for nociceptive information.
AB  - The present paper is aimed at defining distinctive subdivisions of the human
      cuneate nucleus (Cu), evident from prenatal to old life, whose occurrence has
      never been clearly formalized in the human brain, or described in other species
      so far. It extends our early observations on the presence of gray matter areas
      that host strong substance P (SP) immunoreactivity in the territory of the human
      Cu and adjacent cuneate fascicle. Here we provide a three-dimensional
      reconstruction of the Cu fields rich in SP and further identify those areas by
      means of their immunoreactivity to the neuropeptides SP, calcitonin gene-related
      peptide, methionine- and leucine-enkephalin, peptide histidine-isoleucine,
      somatostatin and galanin, to the trophins glial cell line-derived neurotrophic
      factor and brain-derived neurotrophic factor, and to the neuroplasticity proteins
      polysialylated neural cell adhesion molecule and growth-associated protein-43.
      The presence, density and distribution of immunoreactivity for each of these
      molecules closely resemble those occurring in the superficial layers of the
      caudal spinal trigeminal nucleus (Sp5C). Myelin and Nissl stainings suggest that
      those Cu subregions and the Sp5C superficial layers share a similar histological
      aspect. This work establishes the existence of definite subregions, localized
      within the Cu territory, that bear the neurochemical and histological features of
      sensory nuclei committed to the neurotransmission of protopathic stimuli,
      including pain. These findings appear of particular interest when considering
      that functional, preclinical and clinical studies show that the dorsal column
      nuclei, classical relay station of fine somatic tactile and proprioceptive
      sensory stimuli, are also involved in pain neurotransmission. 

PMID- 23975347
TI  - Long-term cultured hairy roots of chicory-a rich source of hydroxycinnamates and
      8-deoxylactucin glucoside.
AB  - A 12-year-old hairy root culture of Cichorium intybus L., a callus culture of the
      plant as well as roots and leaves of a wild plant of chicory, and roots of two C.
      intybus L. var. sativum cultivars were examined in respect of their
      hydroxycinnamate and sesquiterpene lactone compositions and contents. Total
      phenolics and diphenylpicrylhydrazyl radical scavenging activity of the examined
      plant tissues were also analyzed. The most active in radical scavenging were
      extracts from the hairy roots and leaves of chicory. 3,5-Dicaffeoylquinic acid
      was the major antioxidant present in the hairy roots. Its content in the root
      biomass reached 5.5 %, calculated on a dry weight basis. 8-Deoxylactucin
      glucoside (crepidiaside A) was the major sesquiterpene lactone in the hairy
      roots. Its content reached 1.4 %, calculated on a dry weight basis, and was
      nearly two orders of magnitude higher than that in the roots of wild chicory
      plant. The glucosidic derivative of 8-deoxylactucin constituted over 85 % of the
      total sesquiterpene lactone content in the long-term cultured hairy roots of
      chicory. Aglycone of this compound was reported to possess anti-inflammatory
      activity. The qualitative and quantitative analyses of hydroxycinnamates in
      callus and hairy root cultures of C. intybus were undertaken for the first time.

PMID- 23975349
TI  - Backbone and side-chain 1H, 15N, and 13C resonance assignments of the microtubule
      binding domain of yeast cytoplasmic dynein in the high and low-affinity states.
AB  - Cytoplasmic dynein is a motor protein that walks toward the minus end of
      microtubules (MTs) by utilizing the energy of ATP hydrolysis. The heavy chain of
      cytoplasmic dynein contains the microtubule-binding domain (MTBD). Switching of
      MTBD between high and low affinity states for MTs is crucial for processive
      movement of cytoplasmic dynein. Previous biochemical studies demonstrated that
      the affinity of MTBD is regulated by the AAA+ family ATPase domain, which is
      separated by 15 nm long coiled-coil helix. In order to elucidate the structural
      basis of the affinity switching mechanism of MTBD, we designed two MTBD
      constructs, termed MTBD-High and MTBD-Low, which are locked in high and low
      affinity state for MTs, respectively, by introducing a disulfide bond between the
      coiled-coil helix. Here, we established the backbone and side-chain assignments
      of MTBD-High and MTBD-Low for further structural analyses.

PMID- 23975350
TI  - Detection of apoptotic keratinocytes in a case of bullous pemphigoid developed
      after graft-versus-host disease.

PMID- 23975351
TI  - Video game violence use among "vulnerable" populations: the impact of violent
      games on delinquency and bullying among children with clinically elevated
      depression or attention deficit symptoms.
AB  - The issue of children's exposure to violent video games has been a source of
      considerable debate for several decades. Questions persist whether children with
      pre-existing mental health problems may be influenced adversely by exposure to
      violent games, even if other children are not. We explored this issue with 377
      children (62 % female, mixed ethnicity, mean age = 12.93) displaying clinically
      elevated attention deficit or depressive symptoms on the Pediatric Symptom
      Checklist. Results from our study found no evidence for increased bullying or
      delinquent behaviors among youth with clinically elevated mental health symptoms
      who also played violent video games. Our results did not support the hypothesis
      that children with elevated mental health symptoms constitute a "vulnerable"
      population for video game violence effects. Implications and suggestions for
      further research are provided. 

PMID- 23975352
TI  - Trajectories of depressive symptoms from adolescence to young adulthood: the role
      of self-esteem and body-related predictors.
AB  - Although depression is a common issue among youth, it is unclear how important
      developmental factors, such as body mass index (BMI), self-esteem, and eating-and
      weight-related disturbances relate to the development of depression across
      adolescence and into young adulthood. Gender differences in these relationships
      and the specific nature of these relationships among adolescent boys and young
      men require further study. Using multilevel growth curve modeling, this study
      examined the effects of BMI, self-esteem, and eating- and weight-related
      disturbances (i.e., body dissatisfaction and weight management effort) and their
      interactive effects with gender on the developmental trajectory of depressive
      symptoms using the Canadian-based National Longitudinal Survey of Children and
      Youth (N = 4,359 ages 12-21, 48.7 % female). On average, depressive symptoms
      decreased slightly at ages 12 through 14, began to increase from ages 14 through
      17, and then began to decrease through age 21. Adolescent girls were at increased
      risk for depressive symptoms throughout adolescence and young adulthood compared
      to boys. This effect was compounded by low levels of self-esteem across
      adolescence and young adulthood. Engaging in weight management effort was
      associated with lower initial levels of depressive symptoms in early adolescence.
      The study's findings contribute to basic etiologic research regarding the
      trajectory of depressive symptoms in adolescence and young adulthood suggesting
      that mid-adolescents may be most vulnerable to depression compared to other
      adolescent age groups. The findings also underscore the importance of fostering
      positive self-esteem among adolescent girls and young women to prevent depression
      and exploring the protective effect of specific weight management strategies in
      future research.

PMID- 23975353
TI  - Processes linking parents' and adolescents' religiousness and adolescent
      substance use: monitoring and self-control.
AB  - Empirical evidence suggests that religiousness is related negatively to
      adolescent substance use; yet, we know little about how such protective effects
      might occur. The current study examined whether parents' and adolescents'
      religiousness are associated positively with parental, religious, and self
      monitoring, which in turn are related to higher self-control, thereby related to
      lower adolescent substance use. Participants were 220 adolescents (45 % female)
      who were interviewed at ages 10-16 and again 2.4 years later. Structural equation
      modeling analyses suggested that higher adolescents' religiousness at Time 1 was
      related to lower substance use at Time 2 indirectly through religious monitoring,
      self-monitoring, and self-control. Higher parents' religiousness at Time 1 was
      associated with higher parental monitoring at Time 2, which in turn was related
      to lower adolescent substance use at Time 2 directly and indirectly through
      higher adolescent self-control. The results illustrate that adolescents with high
      awareness of being monitored by God are likely to show high self-control
      abilities and, consequently, low substance use. The findings further suggest that
      adolescents' religiousness as well as their religious environments (e.g.,
      familial context) can facilitate desirable developmental outcomes.

PMID- 23975354
TI  - Concurrent trajectories of change in adolescent and maternal depressive symptoms
      in the TORDIA study.
AB  - Depression has a heightened prevalence in adolescence, with approximately 15 % of
      adolescents experiencing a major depressive episode by age 18. Depression in
      adolescence also poses a risk for future distress and impairment. Despite
      treatment advances, many adolescents relapse after initial remission. Family
      context may be an important factor in the developmental trajectory of adolescent
      depression, and thus in enhancing treatment. This study examined concurrent
      change over time in adolescent and maternal depressive symptoms in the context of
      the Treatment of Resistant Depression in Adolescents study. Participants were 334
      adolescents (mean age: 16; SD: 1.6; 70 % female, 84 % Caucasian), and their
      mothers (n = 241). All adolescents were clinically depressed when they entered
      the study and had received previous selective serotonin reuptake inhibitor (SSRI)
      treatment. Adolescents received acute treatment for 12 weeks and additional
      treatment for 12 more weeks. Adolescent depression and suicidal ideation were
      assessed at 0, 6, 12, 24, 48 and 72 weeks, while maternal depressive symptoms
      were assessed at 0, 12, 24, 48 and 72 weeks. Latent basis growth curve analyses
      showed a significant correlation over 72 weeks between trajectories of maternal
      and adolescent depressive symptoms, supporting the hypothesis of concurrent
      patterns of change in these variables. The trajectories were correlated more
      strongly in a subsample that included only dyads in which mothers reported at
      least one depressive symptom at baseline. Results did not show a correlation
      between trajectories of maternal depressive symptoms and adolescent suicidal
      ideation. These findings suggest that adolescent and maternal depressive symptoms
      change in tandem, and that treatment for adolescent depression can benefit the
      wider family system. Notably, most mothers in this sample had subclinical
      depressive symptoms. Future research might explore these trajectories in dyads
      with more severely depressed mothers.

PMID- 23975355
TI  - Structural and dynamical characterization of the Miz-1 zinc fingers 5-8 by
      solution-state NMR.
AB  - Myc-interacting zinc finger protein-1 (Miz-1) is a BTB/POZ transcription factor
      that activates the transcription of cytostatic genes, such as p15(INK4B) or
      p21(CIP1). The C-terminus of Miz-1 contains 13 consensus C2H2 zinc finger domains
      (ZF). ZFs 1-4 have been shown to interact with SMAD3/4, while the remaining ZFs
      are expected to bind the promoters of target genes. We have noted unusual
      features in ZF 5 and the linker between ZFs 5 and 6. Indeed, a glutamate is found
      instead of the conserved basic residue two positions before the second zinc
      coordinating histidine on the ZF 5 helix, and the linker sequence is DTDKE in
      place of the classical TGEKP sequence. In a canonical betabetaalpha fold, such
      unusual primary structure elements should cause severe electrostatic repulsions.
      In this context, we have characterized the structure and the dynamics of a Miz-1
      construct comprising ZFs 5-8 (Miz 5-8) by solution-state NMR. Whilst ZFs 5, 7 and
      8 were shown to adopt the classical betabetaalpha fold for C2H2 ZFs, the number
      of long-range NOEs was insufficient to define a classical fold for ZF 6. We show
      by using (15)N-relaxation dispersion experiments that this lack of NOEs is due to
      the presence of extensive motions on the MUs-ms timescale. Since this negatively
      charged region would have to be located near the phosphodiester backbone in a DNA
      complex, we propose that in addition to promoting conformational searches, it
      could serve as a hinge region to keep ZFs 1-4 away from DNA.

PMID- 23975356
TI  - Improved chemical shift based fragment selection for CS-Rosetta using Rosetta3
      fragment picker.
AB  - A new fragment picker has been developed for CS-Rosetta that combines beneficial
      features of the original fragment picker, MFR, used with CS-Rosetta, and the
      fragment picker, NNMake, that was used for purely sequence based fragment
      selection in the context of ROSETTA de-novo structure prediction. Additionally,
      the new fragment picker has reduced sensitivity to outliers and other difficult
      to match data points rendering the protocol more robust and less likely to
      introduce bias towards wrong conformations in cases where data is bad, missing or
      inconclusive. The fragment picker protocol gives significant improvements on 6 of
      23 CS-Rosetta targets. An independent benchmark on 39 protein targets, whose NMR
      data sets were published only after protocol optimization had been finished, also
      show significantly improved performance for the new fragment picker (van der
      Schot et al. in J Biomol NMR, 2013).

PMID- 23975357
TI  - Discrete subaortic stenosis diagnosed intraoperatively.

PMID- 23975358
TI  - Immunogenicity, the elephant in the room. Comment on "Drug levels, anti-drug
      antibodies and clinical efficacy of the anti-TNFalpha biologics in rheumatic
      diseases".

PMID- 23975359
TI  - Assessment of the dimensions, construct validity, and utility for rheumatoid
      arthritis screening of the COPCORD instrument.
AB  - This study aims to evaluate the structural validity of the Community-Oriented
      Program for the Control of Rheumatic Diseases (COPCORD) core instrument as a
      screening tool for rheumatoid arthritis (RA) by means of assessing the existence
      of domains in the questionnaire. The Mexican version of the COPCORD instrument
      was applied to individuals over18 years of age in five regions of the country
      through a probabilistic/convenience household survey. Clinical confirmation of RA
      diagnosis was used. The variables analyzed included self-reported comorbidities
      and manifestations of the disease, as well as sociodemographic characteristics.
      The statistical approach was based on polychoric exploratory factor analysis and
      confirmatory factor analysis by means of probit structural equation models. A
      total of 19,213 subjects were included in the analysis. The average age for the
      total sample was 42.89 years old; 40.64 % of the subjects were older than 45
      years of age and 20.42 % older than 55. More than 80 % of the variation was
      related to three underlying factors: recent pain, historical pain, and
      disability. The findings verified the usefulness of the COPCORD instrument as a
      screening tool for RA. The results also allowed to characterize how the variation
      in terms of manifestations of the disease could be accounted for diagnosing the
      disease in the Mexican context and examined the capabilities of the instrument to
      measure correctly the main characteristics of patients suffering from RA. 

PMID- 23975360
TI  - The role of hemostatic mechanisms in the development of thrombosis in Behcet's
      disease: an analysis by modified rotation thromboelastogram (ROTEM).
AB  - Behcet's disease (BD) is a multisystemic disorder characterised by recurrent oral
      and genital ulcers. Vasculitis and thrombotic events are the most important
      causes of mortality. Thrombosis is the major clinical finding in patients with
      BD, but the cause of the thrombosis is still unclear. Thromboelastography is an
      alternative method to evaluate almost all steps of the hemostatic system. Today,
      the modified rotation thromboelastogram (ROTEM) is a newer coagulation test and a
      more powerful technique. Our aim in this study was to investigate whether
      hemostatic mechanisms play a role in the development of thrombosis in BD patients
      by using ROTEM. Thirty BD patients, 20 ankylosing spondylitis patients, and 14
      healthy controls who are not taking anti-aggregant or anti-coagulant therapy were
      included in the study. Whole blood count, protrombin time, activated protrombin
      time, fibrinogen, D-dimer levels, and ROTEM parameters (clotting time, clot
      formation time (CFT), and maximum clot formation(MCF)) were determined by INTEM
      and EXTEM analysis. Of the 30 patients with BD, 19 were women and 11 were men,
      and mean age was 40.6 +/- 11.2. Two of the BD patients had vascular involvement,
      but none of them were in active phase of the disease during the study. In INTEM
      assay, MCF (p < 0,001) value was significantly increased, and CFT (p>0.05) value
      was decreased in BD patients compared with the control group. In the EXTEM assay,
      there was a similar significant increase in MCF (p=0.002) value and a decrease in
      CFT (p=0.002) value in BD patients compared with the control group. The results
      of our study indicated that primary hemostatic mechanisms which can be detected
      by ROTEM may play a role in the development of thrombosis in patients with BD.

PMID- 23975361
TI  - Cross-cultural adaptation and validation of the Brazilian version of the
      Scleroderma Health Assessment Questionnaire (SHAQ).
AB  - The Scleroderma Health Assessment Questionnaire (SHAQ) is a feasible multisystem
      specific tool that has been extensively used as an additional assessment for
      systemic sclerosis (SSc). The aim of this study is to cross-culturally adapt and
      validate the Brazilian version of the SHAQ. Construct validity was assessed based
      on the correlations between SHAQ and both the Medical Outcomes Survey Short Form
      36 version 2 (SF-36v2TM) and the Health Assessment Questionnaire Disability Index
      (HAQ-DI). The correlation between the SHAQ and disease severity was assessed by
      Spearman's correlation coefficient. The reproducibility of the SHAQ was evaluated
      by the intraclass correlation coefficient (ICC). Among the 151 consecutive
      outpatients evaluated, 59 % had limited SSc subtype. The overall disease severity
      visual analog scale (VAS) of the SHAQ was statistically significantly correlated
      to HAQ-DI, pain VAS, and the SF-36v2TM physical component summary score (r =
      0.595, r = 0.612, and r = -0.582, respectively; p < 0.001). Further analysis of
      all SF-36v2TM components revealed statistically significant correlations between
      overall disease severity VAS and bodily pain (r = -0.621, p < 0.001), vitality (r
      = -0.544, p < 0.001), physical function (r = -0.510, p < 0.001), and role
      limitation-physical dimensions (r = -0.505, p < 0.001). Moreover, digestive,
      pulmonary, and overall disease severity VASs were statistically significantly
      correlated to the number of organs involved (r = 0.178, p = 0.029; r = 0.214, p =
      0.008; r = 0.282, p < 0.001). We also demonstrated high reproducibility for SHAQ
      (ICC = 0.757, 95 % confidence interval = 0.636-0.842). The Brazilian version of
      the SHAQ demonstrated both construct and discriminant validities as well as good
      reproducibility. 

PMID- 23975362
TI  - Predictors for health improvement in patients with fibromyalgia: a 2-year follow
      up study.
AB  - Fibromyalgia (FM) has a high impact on all aspects of health. The effect from
      interventions is usually small and characterized by uncertainty. Better insight
      in predictors for improved health is essential. The present study aimed to
      understand predictors for patient global impression of change and changes in
      overall health. Data from a longitudinal cohort of recently diagnosed FM patients
      (n = 203) were used. Within this cohort, patients were pre-randomized to either a
      multidisciplinary (n = 108) or an, aerobic exercise (n = 47) program, or usual
      care (n = 48). Only a limited number of patients started with the programs (n =
      86) or participated fully, i.e., attended >70 % of the scheduled sessions (n =
      68). Patients completed questionnaires covering all components of the
      International Classification of Functioning, Disability and Health (ICF) bio
      psycho-social model of health, which was used as a framework to structure
      potential predictors. Principal component analysis was used to reduce the number
      of potential predictors. Regression analyses were used to explore associations
      with the outcome variables. Principal component analysis yielded five factors
      representing areas that covered different ICF components and chapters. "Being
      employed" and "full participation in a program" were independently associated
      with a better global impression of change. A longer duration of FM-related
      symptoms and more limitations in physical areas of body functions were
      independently associated with a worse impression of overall health. Higher levels
      of perceived limitations in physical and mental activities were associated with
      "starting to participate in a program" and with "full participation in a
      program." Recently diagnosed FM patients that report fewer physical limitations
      may experience more improvement in health if they are at work and have a positive
      attitude towards participating in an offered health-care intervention. These
      findings give support to an active rather than to a care-avoiding attitude of
      health-care workers in their contacts to these patients. 

PMID- 23975363
TI  - Long-term safety of anti-TNF-alpha in PsA patients with concomitant HCV
      infection: a retrospective observational multicenter study on 15 patients.
AB  - Psoriatic arthritis (PsA) is an inflammatory arthropathy associated with skin
      and/or nail psoriasis. TNF-alpha, in addition to its pro-inflammatory role, is an
      essential cytokine for the host's defense, and its depletion by treatment may
      facilitate the risk of viral infections or their reactivation. The aim of this
      study was to evaluate the efficacy and safety of TNF-alpha blockers in PsA
      patients with concurrent hepatitis C virus (HCV) infection. This is a multicenter
      study carried out in four Italian centers specialized in the diagnosis and
      treatment of PsA. At baseline and after 6 (T6) and 12 months (T12) of therapy,
      data concerning PsA activity and liver tests were registered. A total of 15 PsA
      patients with concomitant HCV infection were included in the study. At baseline,
      13 patients had low viral load, and liver enzyme tests were within the normal
      range. During the observation period, these values remained stable. On the other
      hand, at baseline, a high viral load with slightly increased values of AST and
      ALT was detected in one patient. At T6 and T12, these values decreased. The
      remaining patient, at baseline, had low viral load, but with slightly increased
      AST and ALT values that normalized during the observation period. This is the
      greatest sample size available in the literature on this topic. The data suggests
      that anti-TNF-alpha agents are effective and safe in PsA patients with
      concomitant HCV. We suggest that the use of anti-TNF-alpha agents, accompanied by
      close monitoring, could be a therapeutic option.

PMID- 23975364
TI  - Meta-analysis: glutathione S-transferase T1 null allele is associated with
      gastric cancer risk.
AB  - Allelic variant within genes encoding glutathione S-transferase T1 (GSTT1) has
      been suggested to be a possible risk factor of gastric cancer, but previous
      studies provide controversial results. This study aimed to assess the effects of
      GSTT1 polymorphism on gastric cancer by means of meta-analysis. We included
      published studies on the relationship between GSTT1 null allele and gastric
      cancer risk after searching electronic databases. A meta-analysis was conducted
      by calculating the pooled odds ratios (OR) and the 95% confidence intervals (95%
      CI). Forty-two studies with a total of 8,203 gastric cancer cases and 13,866
      controls were included into this meta-analysis. When all 42 studies were pooled
      into this meta-analysis, there was a significant association between the GSTT1
      null allele and gastric cancer risk (OR = 1.24, 95% CI 1.14-1.36, P < 0.00001).
      Sensitivity analysis by excluding individual studies showed that there was no
      effect on the pooled OR with 95% CI. After excluding studies with low quality,
      there was still a significant association between the GSTT1 null allele and
      gastric cancer risk (OR = 1.24, 95% CI 1.13-1.36, P < 0.00001). In the subgroup
      analysis, there was a significant association between the GSTT1 null allele and
      gastric cancer risk in both Europeans and Asians. There was no risk of
      publication bias in this meta-analysis. Our results suggest that GSTT1 null
      allele is associated with increased risk of gastric cancer.

PMID- 23975366
TI  - Association between GSTP1 Ile105Val polymorphism and glioma risk: a systematic
      review and meta-analysis.
AB  - Glutathione S-transferase P1 (GSTP1) gene Ile105Val polymorphism has been
      suggested to be involved in the development of glioma. However, the results from
      the studies regarding the association between GSTP1 Ile105Val polymorphism and
      glioma risk have been inconsistent. Thus, we performed a meta-analysis to
      investigate this association. Pooled odds ratios (ORs) with 95% confidence
      intervals (95%CIs) were calculated using random or fixed effects model. Nine
      studies with 2,078 cases and 3,970 controls were finally included into this meta
      analysis. The results suggested there was no association between GSTP1 Ile105Val
      polymorphism and glioma risk under recessive model (OR = 1.138, 95%CI = 0.966
      1.341, Pheterogeneity = 0.088, P = 0.123). Subgroup analyses by ethnicity showed
      there was also no association between GSTP1 Ile105Val polymorphism and glioma
      risk in mixed populations under recessive model (OR = 1.199, 95%CI = 0.928-1.549,
      Pheterogeneity = 0.060, P = 0.166) and Caucasian populations (OR = 1.097, 95%CI =
      0.885-1.360, Pheterogeneity = 0.186, P = 0.398). In conclusion, the meta-analysis
      suggests that there is no association between GSTP1 Ile105Val polymorphism and
      glioma risk. However, more well-designed and larger studies are needed to further
      assess this association.

PMID- 23975365
TI  - The rs1050450 C > T polymorphism of GPX1 is associated with the risk of bladder
      but not prostate cancer: evidence from a meta-analysis.
AB  - Glutathione peroxidase (GPX) is an endogenous antioxidant enzyme counteracting
      oxidative stress. Accumulating evidence has demonstrated that the GPX1 rs1050450
      C > T polymorphism may modulate cancer risk, but the association of GPX1
      rs1050450 polymorphism with bladder cancer (BC) and prostate cancer (PCa) is
      still inconclusive. This meta-analysis was designed to determine the exact
      association of GPX1 rs1050450 C > T polymorphism with the risk of bladder cancer
      and prostate cancer. Odds ratios (ORs) and 95% confidence intervals (CI) were
      calculated to estimate the association strength. Databases of PubMed, EMBASE, and
      China National Knowledge Infrastructure were searched to retrieve eligible
      studies. In total, ten eligible studies with 6,194 participants were included. By
      pooling all eligible studies, we found that carriers of the variant T allele were
      associated with a significantly increased risk of urinary tract cancer (T vs. C:
      OR = 1.459 and 95% CI, 1.086-1.962; CT/TT vs. CC: OR = 1.411 and 95 % CI, 1.053
      1.891). In stratified analysis, we observed that the rs1050450 C > T polymorphism
      was significantly associated with an increased risk of BC (T vs. C: OR = 2.111
      and 95% CI, 1.020-4.368; CT/TT vs. CC: OR = 1.876 and 95% CI, 1.011-3.480), while
      the association was not significant for PCa. Egger's test and Begg's test
      revealed no publication bias. The present meta-analysis provides evidence that
      the GPX1 rs1050450 C > T polymorphism leads to an increased risk of BC but not
      the risk of PCa.

PMID- 23975367
TI  - The effect of oxoguanine glycosylase 1 rs1052133 polymorphism on colorectal
      cancer risk in Caucasian population.
AB  - Human oxoguanine glycosylase 1 (OGG1) is an important part of the base excision
      repair pathway in the DNA repair. Numerous epidemiological studies have evaluated
      the association between OGG1 rs1052133 polymorphism and the risk of colorectal
      cancer, but the results of these studies from the Caucasian population were
      conflicting. To derive a more precise assessment on the association between OGG1
      rs1052133 polymorphism and risk of colorectal cancer in Caucasian population, we
      performed a meta-analysis. The odds ratios (OR) with 95% confidence intervals
      (CI) were used to assess the strength of the association. Thirteen case-control
      studies with a total of 4,103 cases and 5,400 controls were finally included into
      the meta-analysis. Meta-analysis of all 13 studies showed that OGG1 rs1052133
      polymorphism was significantly associated with the risk of colorectal cancer in
      Caucasian population (Cys versus Ser OR = 1.20, 95% CI = 1.03-1.39, P = 0.02;
      CysCys versus SerSer OR = 1.44, 95% CI = 1.04-2.00, P = 0.03; CysCys versus
      SerSer/SerCys OR = 1.39, 95% CI = 1.15-1.67, P = 0.0005). In the sensitivity
      analysis, omitting each study one at a time had no obvious influence on the
      pooled OR, which confirmed the stability of meta-analysis. The meta-analysis
      suggests that OGG1 rs1052133 polymorphism is significantly associated with the
      risk of colorectal cancer in Caucasian population.

PMID- 23975368
TI  - Kruppel-like factor 5: a novel biomarker for lymph node metastasis and recurrence
      in supraglottic squamous cell laryngeal carcinoma.
AB  - Kruppel-like factor 5 (KLF5), a zinc finger-containing transcription factor, is
      involved in important biological processes including cell transformation,
      proliferation, and carcinogenesis. However, its clinical significance has
      remained largely unknown in laryngeal cancer. Here, specimens from 144 patients
      with laryngeal tumors were investigated by immunohistochemical staining for KLF5,
      integrin-linked kinase (ILK), and E-cadherin expressions. A clinicopathological
      study revealed that the KLF5 expression level in tumor cells was significantly
      correlated with lymph node metastasis (P < 0.05) and local recurrence (P < 0.05).
      In addition, KLF5, ILK, and E-cadherin (epithelial-mesenchymal transition (EMT)
      biomarker) expressions were correlated with each other. These findings suggest
      that KLF5 may be an epithelial-mesenchymal transition-associated biomarker in
      human laryngeal carcinomas and play important roles in the progression of
      laryngeal carcinomas. KLF5 immunoreactivity is therefore considered a potential
      lymph node metastasis and recurrence factor in human laryngeal cancers. In
      addition, the KLF5-mediated pathway is a potential target for elimination of
      laryngeal cancer in the future. 

PMID- 23975369
TI  - SMAD4 is a potential prognostic marker in human breast carcinomas.
AB  - SMAD4 is a downstream mediator of transforming growth factor beta. While its
      tumor suppressor function has been investigated as a prognostic biomarker in
      several human malignancies, its role as a prognostic marker in breast carcinoma
      is still undefined. We investigated SMAD4 expression in breast carcinoma samples
      of different histologic grades to evaluate the association between SMAD4 and
      outcome in breast cancer. We also investigated the role of SMAD4 expression
      status in MDA-MB-468 breast cancer cells in responding to TGF-beta stimulation.
      SMAD4 expression was assessed in 53 breast ductal carcinoma samples and in the
      surrounding normal tissue from 50 of the samples using immunohistochemistry,
      Western blot, and real-time PCR. TGF-beta-SMAD and non-SMAD signaling was
      assessed by Western blot in MDA-MB-468 cells with and without SMAD4 restoration.
      SMAD4 expression was reduced in ductal breast carcinoma as compared to
      surrounding uninvolved ductal breast epithelia (p < 0.05). SMAD4 expression
      levels decreased from Grade 1 to Grade 3 ductal breast carcinoma as assessed by
      immunohistochemistry (p < 0.05). Results were recapitulated by tissue array. In
      addition, immunohistochemistry results were further confirmed at the protein and
      mRNA level. We then found that non-SMAD MEK/MAPK signaling was significantly
      different between SMAD4 expressing MDA-MB-468 cells and SMAD4-null MDA-MB-468
      cells. This is the first study indicating that SMAD4 plays a key role in shifting
      MAPK signaling. Further, we have demonstrated that SMAD4 has a potential role in
      the development of breast carcinoma and SMAD4 was a potential prognostic marker
      of breast carcinoma. Our findings further support the role of SMAD4 in breast
      carcinoma development. In addition, we observed an inverse relationship between
      SMAD4 levels and breast carcinoma histological grade. Our finding indicated that
      SMAD4 expression level in breast cancer cells played a role in responding non
      SMAD signaling but not the canonic SMAD signaling. Further mechanistic studies
      are necessary to establish the role of SMAD4 in breast carcinoma prognosis and
      potential specific targeting. 

PMID- 23975370
TI  - TGFbeta1 Leu10Pro polymorphism contributes to the development of prostate cancer:
      evidence from a meta-analysis.
AB  - Transforming growth factor-beta1 (TGFbeta1) plays a significant role in
      regulating cellular proliferation and apoptosis. A large number of studies
      related to the association between TGFbeta1 Leu10Pro polymorphism and prostate
      cancer (PC) risk, but get conflicting results. We performed a meta-analysis based
      on six studies, assessing the strength of the association using odds ratios (OR)
      with 95% confidence intervals (CI). Overall, our evidence has indicated that
      TGFbeta1 Leu10Pro polymorphism had significantly increased PC risk in the allele
      comparison model (OR = 1.081, 95% CI = 1.003-1.165, Pheterogeneity = 0.141, P =
      0.041). In the stratified analysis by ethnicity, the same results were found
      among Caucasians (for heterozygote model, OR = 1.741, 95% CI = 1.004-3.020,
      Pheterogeneity = 0.000, P = 0.049; recessive model, OR = 1.339, 95% CI = 1.045
      1.717, Pheterogeneity = 0.020, P = 0.021; allele comparison model, OR = 1.091,
      95% CI = 1.005-1.184, Pheterogeneity = 0.048, P = 0.037). In conclusion, this
      meta-analysis suggested that TGFbeta1 Leu10Pro polymorphism contributed to the
      development of PC. A well-designed and larger study is still required to evaluate
      this polymorphism and PC risk.

PMID- 23975371
TI  - ARID5B gene rs10821936 polymorphism is associated with childhood acute
      lymphoblastic leukemia: a meta-analysis based on 39,116 subjects.
AB  - Childhood acute lymphoblastic leukemia (ALL) is the leading cause of cancer
      related deaths among children. Two recent genome-wide association studies and
      several replicated studies have provided convincing evidence that inherited
      genetic variation in ARID5B contributes to childhood ALL predisposition. In the
      present study, we performed a meta-analysis to systematically summarize the
      association between ARID5B genetic polymorphism and the risk for ALL. We
      conducted a search of case-control studies on the association of ARID5B genetic
      polymorphisms with susceptibility to ALL in PubMed, EMBASE, Wanfang database in
      China, and Chinese National Knowledge Infrastructure databases. Data from
      eligible studies were extracted for meta-analysis. ALL risk associated with
      ARID5B genetic polymorphism was estimated by pooled odds ratios (ORs) and 95%
      confidence intervals (95% CIs). Nine articles including 13 case-control studies
      were included in the present meta-analysis. We found that rs10821936 polymorphism
      in ARID5B gene was associated with increased risk for ALL (P < 0.0001; OR = 1.27;
      95%CI, 1.17-1.37). This meta-analysis suggests that ARID5B genetic polymorphism
      was associated with the increased risk of ALL.

PMID- 23975372
TI  - Expression of a phosphorylated form of ATF4 in lung and non-small cell lung
      cancer tissues.
AB  - ATF4 is a member of the cAMP-responsive element-binding protein family of basic
      zipper-containing proteins, a family of transcription factors phosphorylated at
      serines residues by protein kinase A. The family has been proved to be able to
      stimulate the transcription of the genes containing CRE elements. Elevated ATF4
      expression was detected in some tumors including breast carcinoma compared to
      their corresponding nontumor tissues. p-ATF4 (ser 245), a phosphorylated form of
      ATF4 protein at serine 245 site, was believed to be an active type of this
      protein. However, its expression and clinical significance in malignant tumors
      including non-small cell lung cancer were not reported up to date. In the current
      study, we investigate the expression of p-ATF4 (ser 245) in non-small cell lung
      cancer using tissue microarray and immunohistochemistry. p-ATF4 (ser 245)
      immunostaining was detected in nucleus and cytoplasm in cancer cells and normal
      lung epithelial cells. Compared to bronchial epithelium and submucosal glands
      (total positive rate, 14.6% (12/82)), there was increased expression of p-ATF4
      (ser 245) in non-small cell lung cancer cells (total positive rate, 42.7%
      (35/82)) (p < 0.05). In addition, increased expression of p-ATF4 (ser 245) was
      associated with lymph node metastasis and advanced TNM stages (III and IV) in non
      small cell lung cancer (p < 0.05). Immunofluorescent staining confirmed nuclear
      and cytoplasmic expression of p-ATF4 (ser 245) in lung and cancer tissues, and
      also in non-small cell lung cancer cell lines including NCI-H157 and LTE cells.
      These results indicate that increased expression of p-ATF4 (ser 245) may
      contribute to cancer development of non-small cell lung cancer and may be a
      potential cancer marker.

PMID- 23975373
TI  - A let-7 KRAS rs712 polymorphism increases colorectal cancer risk.
AB  - Growing evidence has indicated that polymorphism present in the miRNA binding
      site of target gene can alter the ability of miRNAs to bind its target gene and
      modulate the development and progression of cancer. We aimed to investigate the
      association between let-7 KRAS rs712 polymorphism and the risk of colorectal
      cancer (CRC). The let-7 KRAS rs712 was analyzed in a case-control study,
      including 339 CRC patients and 313 age- and sex-matched controls; the
      relationship between the polymorphism and the clinicopathological features of CRC
      was also examined. Individuals carrying the let-7 KRAS rs712 TT genotype and T
      allele had an increased risk of developing CRC (TT vs. GG, adjusted OR = 2.18;
      95% CI, 1.00-4.77; T vs. G, adjusted OR = 1.50; 95% CI, 1.15-1.96). Stratified
      analyses revealed that CRC patients with the let-7 KRAS rs712 TT genotype were
      more likely to have clinical stage III or IV disease (OR = 3.29, 95% CI, 1.32
      8.20) and distant metastasis (OR = 4.70, 95% CI, 1.81-12.25). These findings
      provide evidence that the let-7 KRAS rs712 polymorphism may play crucial roles in
      the etiology of CRC.

PMID- 23975374
TI  - MiR-148a regulates the growth and apoptosis in pancreatic cancer by targeting
      CCKBR and Bcl-2.
AB  - Our previous studies have revealed that miR-148a is downregulated in pancreatic
      cancer. Bioinformatics analysis has shown cholecystokinin-B receptor (CCKBR) and
      B cell lymphoma (Bcl-2) to be potential targets of miR-148a. But the
      pathophysiologic role of miR-148a and its relevance to the growth and development
      of pancreatic cancer are yet to be investigated. The purpose of this study is to
      elucidate the molecular mechanisms where miR-148a acts as a tumor suppressor in
      pancreatic cancer. Our results showed significant downregulation of miR-148a in
      28 pancreatic cancer tissue samples and five pancreatic cancer cell lines,
      compared with their non-tumor counterparts by qRT-PCR. MiR-148a was found to not
      only inhibit the proliferation of pancreatic cancer cells (PANC-1 and AsPC-1) in
      vitro by MTT assay and colony formation assay, but also to promote cells
      apoptosis in vitro by Annexin V-FITC apoptosis detection and caspase activity
      assay. Using western blot and luciferase activity assay, CCKBR and Bcl-2 were
      identified as targets of miR-148a. Moreover, we also found that the expression of
      Bcl-2 lacking in 3'UTR could abrogate the pro-apoptosis function of miR-148a.
      These findings suggest the importance of miR-148a's targeting of CCKBR and Bcl-2
      in the regulation of pancreatic cancer growth and apoptosis. 

PMID- 23975375
TI  - Swedish experience-based value sets for EQ-5D health states.
AB  - PURPOSE: To estimate Swedish experience-based value sets for EQ-5D health states
      using general population health survey data. METHODS: Approximately 45,000
      individuals valued their current health status by means of time trade off (TTO)
      and visual analogue scale (VAS) methods and answered the EQ-5D questionnaire,
      making it possible to model the association between the experience-based TTO and
      VAS values and the EQ-5D dimensions and severity levels. The association between
      TTO and VAS values and the different severity levels of respondents' answers on a
      self-rated health (SRH) question was assessed. RESULTS: Almost all dimensions
      (except usual activity) and severity levels had less impact on TTO valuations
      compared with the UK study based on hypothetical values. Anxiety/depression had
      the greatest impact on both TTO and VAS values. TTO and VAS values were
      consistently related to SRH. The inclusion of age, sex, education and
      socioeconomic group affected the main effect coefficients and the explanatory
      power modestly. CONCLUSIONS: A value set for EQ-5D health states based on Swedish
      valuations has been lacking. Several authors have recently advocated the
      normative standpoint of using experience-based values. Guidelines of economic
      evaluation for reimbursement decisions in Sweden recommend the use of experience
      based values for QALY calculations. Our results that anxiety/depression had the
      greatest impact on both TTO and VAS values underline the importance of mental
      health for individuals' overall HRQoL. Using population surveys is in line with
      recent thinking on valuing health states and could reduce some of the focusing
      effects potentially appearing in hypothetical valuation studies.

PMID- 23975376
TI  - A framework for understanding quality of life in individuals without capacity.
AB  - PURPOSE: The wide range of tools and methods developed for measuring and valuing
      health-related quality of life for use in economic evaluations are appropriate
      for use in most populations. However, for certain populations, specific tools may
      need to be developed to reflect the particular needs of that population. Patients
      without capacity--particularly patients with severe dementia--are such a
      population. At present, the tools available to economists for measuring and
      valuing quality of life in these patients lack validity. Here, we seek to
      understand the framework within which common instruments have been developed,
      critique these instruments with respect to patients with severely restricted
      capacity and to develop a new way of thinking about how to value health-related
      quality of life in such patients. METHOD: In this essay, we describe and critique
      the conceptual framework by which common instruments used for measuring and
      valuing quality of life have been developed. RESULTS: We show that current common
      instruments used for measuring and valuing quality of life in general populations
      are not appropriate for populations with severely restricted capacity.
      CONCLUSIONS: We propose a new framework for thinking about quality of life in
      this population, based on notions of observable person-centred outcomes and
      utility derived from processes of care.

PMID- 23975377
TI  - Is a diabetes pay-for-performance program cost-effective under the National
      Health Insurance in Taiwan?
AB  - PURPOSE: In October 2001, a pay-for-performance (P4P) program for diabetes was
      implemented by the National Health Insurance (NHI), a single-payer program, in
      Taiwan. However, only limited information is available regarding the influence of
      this program on the patient's health-related quality of life. The aim of this
      study was to estimate the costs and consequences of enrolling patients in the P4P
      program from a single-payer perspective. METHODS: A retrospective observational
      study of 529 diabetic patients was conducted between 2004 and 2005. The data used
      in the study were obtained from the National Health Interview Survey (NHIS) in
      Taiwan. Direct cost data were obtained from NHI claims data, which were linked to
      respondents in the NHIS using scrambled individual identification. The generic
      SF36 health instrument was employed to measure the quality-of-life-related health
      status and transformed into a utility index. Patients enrolled in the P4P program
      for at least 3 months were categorized as the P4P group. Following propensity
      score matching, 260 patients were included in the study. Outcomes included life
      years, quality-adjusted life-years (QALYs), diabetes-related medical costs,
      overall medical costs, and incremental cost-effectiveness ratios (ICERs). A
      single-payer perspective was assumed, and costs were expressed in US dollars.
      Nonparametric bootstrapping was conducted to estimate confidence intervals for
      cost-effectiveness ratios. RESULTS: Following matching, no significant difference
      was noted between two groups with regard to the patients' age, gender, education,
      family income, smoking status, BMI, or whether insulin was used. The P4P group
      had an increase of 0.08 (95 % CI 0.077-0.080) in QALYs, and the additional
      diabetes-related medical cost was US$422.74 (95 % CI US$413.58-US$435.05),
      yielding an ICER of US$5413.93 (95 % CI US$5226.83-US$5562.97) per QALY gained.
      CONCLUSIONS: Our results provides decision makers with valuable information
      regarding the impact of the P4P program of diabetes care through a direct
      comparison of equivalent groups of patients receiving regular care. Under the
      single-payer NHI system, the use of financial incentives under the DM-P4P program
      may be an effective means to ensure the quality of follow-up treatment.

PMID- 23975378
TI  - How to measure quality of life in shared-housing arrangements? A comparison of
      dementia-specific instruments.
AB  - PURPOSE: The appropriateness of existing quality of life (QoL) instruments in
      small-scale, homelike care facilities for people with dementia is as yet unknown.
      This study evaluated the psychometric properties of three QoL instruments in
      German shared-housing arrangements (SHA). METHOD: A cross-sectional study was
      conducted in 36 SHA in Berlin to evaluate the acceptability, internal
      consistency, and validity (construct, convergent, and discriminant) of three QoL
      instruments: Alzheimer's Disease Related Quality of Life (ADRQL), Quality of Life
      Alzheimer's Diseases (QoL-AD), and measuring QUAlity of LIfe in DEMentia
      (QUALIDEM). RESULTS: A total of 104 residents (mean age 79.0 years, 73 % female)
      were included. All instruments showed good acceptability, with QUALIDEM the best.
      Adequate levels of internal consistency for the ADRQL and QoL-AD and most of the
      QUALIDEM domains were found. Validity of all the instruments measuring QoL was
      confirmed. CONCLUSIONS: Study findings suggest that QUALIDEM is the preferred
      instrument to evaluate QoL of residents in SHA, especially due to the high
      acceptability. Further research is needed to develop and improve these existing
      measurements.

PMID- 23975379
TI  - Consequences of visual height intolerance for quality of life: a qualitative
      study.
AB  - PURPOSE: Visual height intolerance (vHI) occurs when a trigger causes the
      apprehension of losing balance and falling. Depending on the severity of vHI, an
      avoidance behavior may develop in about 50 % of the thus afflicted, and it can
      have considerable impact on their daily life and interpersonal interactions. It
      seems obvious that such experiences may be impairing and distressing, but this
      has not yet been examined systematically. Objective of this study was to examine
      the consequences of vHI for quality of life. METHODS: A qualitative,
      phenomenological exploratory approach was chosen. Individual face-to-face
      interviews were conducted with individuals who had reported in a previous study
      that they were susceptible to vHI. The interview transcripts were segregated into
      distinct meaning units, which were used to create a coding guideline with meta-
      and subcodes. Meaning units were then systematically extracted and assigned to
      the appropriate codes. Weights and links were used to assign priorities for
      interpretation. RESULTS: Eighteen participants were interviewed (mean age 53,
      range 30-73; 11 females). Data analysis resulted in 29 meta-codes and 115
      subcodes. Responses indicated that vHI can be very disabling and has a relevant
      impact on quality of life and daily activities of the affected persons, including
      their family life and behavior towards partner, children and friends. CONCLUSION:
      Relevant topics for further quantitative studies were identified, for example,
      strategies of compensation and the influence of vHI on family life. Other
      quantitative studies should determine whether comorbidities and the typologies
      found in this study have consequences for individual therapeutic approaches.

PMID- 23975380
TI  - Cross-cultural adaptation and validation of the Manchester Foot Pain and
      Disability Index into Spanish.
AB  - PURPOSE: The Manchester Foot Pain and Disability Index (MFPDI) is a self
      assessment 19-item questionnaire developed in the UK to measure foot pain and
      disability. This study aimed at conducting cross-cultural adaptation and
      validation of the MFPDI for use in Spain. METHODS: Principles of good practice
      for the translation and cultural adaptation process for patient-reported outcomes
      measures were followed in the MFPDI adaptation into Spanish. The cross-cultural
      validation involved Rasch analysis of pooled data sets from Spain and the UK.
      RESULTS: Spanish data set comprised 338 patients, five used in the adaptation
      phase and 333 in the cross-cultural validation phase, mean age (SD) = 55.2 (16.7)
      and 248 (74.5 %) were female. A UK data set (n = 682) added in the cross-cultural
      validation phase; mean age (SD) = 51.6 (15.2 %) and 416 (61.0 %) were female. A
      preliminary analysis of the 17-item MFPDI revealed significant local dependency
      of items causing significant deviation from the Rasch model. Grouping all items
      into testlets and re-analysing the MFPDI as a 3-testlet scale resulted in an
      adequate fit to the Rasch model, chi (2) (df) = 15.945 (12), p = 0.194, excellent
      reliability and unidimensionality. Lack of cross-cultural invariance was evident
      on the functional and personal appearance testlets. Splitting the affected
      testlets discounted the cross-cultural bias and satisfied requirements of the
      Rasch model. Subsequently, the MFPDI was calibrated into interval-level scales,
      fully adjusted to allow parametric analyses and cross-cultural data comparisons
      when required. CONCLUSIONS: Rasch analysis has confirmed that the MFPDI is a
      robust 3-subscale measure of foot pain, function and appearance in both its
      English and Spanish versions.

PMID- 23975381
TI  - Fatigue interference with daily living among patients with inflammatory bowel
      disease.
AB  - PURPOSE: The purpose of the study was to examine fatigue interference with daily
      living in patients with inflammatory bowel disease (IBD) and to explore
      relationships between severe fatigue interference and socio-demographic and
      clinical variables, including use of complementary and alternative medicine
      (CAM). METHODS: Data were collected using self-report questionnaires from adult
      IBD outpatients. Fatigue interference was assessed with the 5-item Fatigue
      Severity Scale, and scores >= 5 were defined as severe fatigue interference. CAM
      use was assessed with the International CAM Questionnaire. Multivariate logistic
      regression analysis was used to examine associations between severe fatigue
      interference and socio-demographic factors, clinical factors, and CAM use.
      RESULTS: In total, 428 patients had evaluable questionnaires (response rate 93
      %). Severe fatigue interference was reported by 39 % of the total sample.
      Patients with Crohn's disease (CD) (n = 238) were more likely than patients with
      ulcerative colitis (UC) (n = 190) to report severe fatigue interference (43 and
      33 %, respectively, p = 0.003). In addition, patients reporting severe fatigue
      interference were more likely to have active disease than patients without severe
      fatigue interference (p < 0.001 for both diagnoses). Patients with inactive
      disease had scores comparable to the general population. Factors independently
      associated with severe fatigue interference in UC included disease activity and
      CAM use, while in CD they included disease activity and current smoking.
      CONCLUSIONS: Severe fatigue interference is common among IBD patients with active
      disease. Among patients with UC, but not CD, CAM use was associated with severe
      fatigue interference. The relationship between fatigue interference and personal
      factors should be considered further in subsequent studies.

PMID- 23975383
TI  - On the characterization of a non-Newtonian blood analog and its response to
      pulsatile flow downstream of a simplified stenosis.
AB  - Particle image velocimetry (PIV) was used to investigate the influence of a non
      Newtonian blood analog of aqueous xanthan gum on flow separation in laminar and
      transitional environments and in both steady and pulsatile flow. Initial steady
      pressure drop measurements in laminar and transitional flow for a Newtonian
      analog showed an extension of laminar behavior to Reynolds number (Re) ~ 2900 for
      the non-Newtonian case. On a macroscale level, this showed good agreement with
      porcine blood. Subsequently, PIV was used to measure flow patterns and turbulent
      statistics downstream of an axisymmetric stenosis in the aqueous xanthan gum
      solution and for a Newtonian analog at Re ~ 520 and Re ~ 1250. The recirculation
      length for the non-Newtonian case was reduced at Re ~ 520 resultant from
      increased viscosity at low shear strain rates. At Re ~ 1250, peak turbulent
      intensities and turbulent shear stresses were dampened by the non-Newtonian fluid
      in close proximity to the blockage outlet. Although the non-Newtonian case's
      recirculation length was increased at peak pulsatile flow, turbulent shear stress
      was found to be elevated for the Newtonian case downstream from the blockage,
      suggesting shear layer fragmentation and radial transport. Our findings conclude
      that the xanthan gum elastic polymer prolongs flow stabilization, which in turn
      emphasizes the importance of non-Newtonian blood characteristics on the resulting
      flow patterns in such cardiovascular environments.

PMID- 23975382
TI  - Assessment of health-related quality of life 6 years after childhood cochlear
      implantation.
AB  - PURPOSE: To examine the impact of cochlear implant (CI) intervention on health
      related quality of life (HRQOL) assessed by both self- and parent-reported
      measures. METHODS: In this national study of children implanted between ages 6
      months and 5 years, HRQOL of 129 children 6-year post-CI was compared to 62
      internal study (NH1) and 185 external (NH2) samples of hearing children frequency
      matched to the CI group on sociodemographic variables. HRQOL ratings of children
      and their parents in each group, measured using the Child Health and Illness
      Profile-Child Edition, were compared, and their associations with the Family
      Stress Scale were investigated. RESULTS: CI children reported overall and domain
      specific HRQOL that was comparable to both NH1 and NH2 peers. CI parents reported
      worse child scores than NH1 parents in Achievement, Resilience, and Global score
      (p's < 0.01) but similar or better scores than socioeconomically comparable NH2
      parents. Higher family stress was negatively associated with all parent-reported
      HRQOL outcomes (p's < 0.01). Parent-child correlations in HRQOL global scores
      trended higher in CI recipients (r = 0.50) than NH1 (r = 0.42) and NH2 (r = 0.35)
      controls. CONCLUSIONS: CI recipients report HRQOL comparable to NH peers. These
      results, from both child and parent perspective, lend support to the
      effectiveness of CI intervention in mitigating the impact of early childhood
      deafness. Family stress was associated with worse HRQOL, underscoring a potential
      therapeutic target. Parent-child agreement in HRQOL scores was higher for CI
      families than NH families, which may reflect higher caregiver insight and
      involvement related to the CI intervention.

PMID- 23975384
TI  - Effect of hypertension on the closing dynamics and Lagrangian blood damage index
      measure of the b-datum regurgitant jet in a bileaflet mechanical heart valve.
AB  - We hypothesize that the formation of the closing vortex and subsequent b-datum
      regurgitation jet in bileaflet mechanical heart valves is governed by the
      magnitude of the driving mean aortic pressure (MAP), and that this sensitivity
      does impact the blood damage index (BDI) corresponding to platelet activation and
      lysis. High spatial resolution time resolved (1 kHz) as well as phase locked
      particle image velocimetry techniques captured the dynamic leaflet closure and
      regurgitation jet of a model 25 mm St. Jude Medical BMHV. Cell trajectories were
      estimated using Lagrangian particle tracking analysis while the leaflet
      kinematics was quantified by tracking the leaflet tip-position throughout
      closure. The non-principal as well as principal shear stress loading histories
      along each cell trajectory revealed BDI for platelet activation and lysis as a
      function of cell initial position, release time-point, and blood pressure.
      Results show that the leaflet closing time reduces by roughly 10 ms, in response
      to an increase in MAP by 40 mmHg. We report that higher MAP leads to a stronger b
      datum vortex and jet formation. Platelet activation BDI lowers with a higher MAP
      due to reduction in exposure times despite an increase in principal shear stress
      experienced. Platelet lysis BDI however increases with higher MAP. Maximum BDI
      may occur for cells initially in the b-datum zone during the onset of leaflet
      closure. Our results provide a better understanding of BDI of the regurgitant b
      datum jet and sheds light on the potential importance of blood damage testing
      under hypertensive conditions.

PMID- 23975385
TI  - A microcontinuum model for mechanical properties of esophageal tissue:
      experimental methodology and constitutive analysis.
AB  - Accurate material properties of tissues are a key factor for the improvement of
      medical procedures and treatments. Experimental data are essential in order to
      formulate and validate a useful constitutive model for predicting the mechanical
      behavior of tissues in these procedures. This study develops a comprehensive
      experimental protocol at multiple length scale levels in order to obtain stress
      strain curves for esophagus tissue. This paper compares two different models: a
      conventional, non-linear elastic model, and a microcontinuum model based on fiber
      rearrangement. Also, a detailed description of the experimental procedure is
      provided. While the focus was on esophageal tissues, the experimental procedure
      and microcontinuum are considered widely applicable to other samples of soft
      tissue. 

PMID- 23975387
TI  - Capture and exploration of sample quality data to inform and improve the
      management of a screening collection.
AB  - A new approach to the storage, processing, and interrogation of the quality data
      for screening samples has improved analytical throughput and confidence and
      enhanced the opportunities for learning from the accumulating records. The
      approach has entailed the design, development, and implementation of a database
      oriented system, capturing information from the liquid chromatography-mass
      spectrometry capabilities used for assessing the integrity of samples in
      AstraZeneca's screening collection. A Web application has been developed to
      enable the visualization and interactive annotation of the analytical data,
      monitor the current sample queue, and report the throughput rate. Sample purity
      and identity are certified automatically on the chromatographic peaks of interest
      if predetermined thresholds are reached on key parameters. Using information
      extracted in parallel from the compound registration and container inventory
      databases, the chromatographic and spectroscopic profiles for each vessel are
      linked to the sample structures and storage histories. A search engine
      facilitates the direct comparison of results for multiple vessels of the same or
      similar compounds, for single vessels analyzed at different time points, or for
      vessels related by their origin or process flow. Access to this network of
      information has provided a deeper understanding of the multiple factors
      contributing to sample quality assurance. 

PMID- 23975388
TI  - A rapid automatic processing platform for bead label-assisted microarray
      analysis: application for genetic hearing-loss mutation detection.
AB  - Molecular diagnostics using microarrays are increasingly being used in clinical
      diagnosis because of their high throughput, sensitivity, and accuracy. However,
      standard microarray processing takes several hours and involves manual steps
      during hybridization, slide clean up, and imaging. Here we describe the
      development of an integrated platform that automates these individual steps as
      well as significantly shortens the processing time and improves reproducibility.
      The platform integrates such key elements as a microfluidic chip, flow control
      system, temperature control system, imaging system, and automated analysis of
      clinical results. Bead labeling of microarray signals required a simple imaging
      system and allowed continuous monitoring of the microarray processing. To
      demonstrate utility, the automated platform was used to genotype hereditary
      hearing-loss gene mutations. Compared with conventional microarray processing
      procedures, the platform increases the efficiency and reproducibility of
      hybridization, speeding microarray processing through to result analysis. The
      platform also continuously monitors the microarray signals, which can be used to
      facilitate optimization of microarray processing conditions. In addition, the
      modular design of the platform lends itself to development of simultaneous
      processing of multiple microfluidic chips. We believe the novel features of the
      platform will benefit its use in clinical settings in which fast, low-complexity
      molecular genetic testing is required. 

PMID- 23975386
TI  - Aryl hydrocarbon receptor promotes RORgammat+ group 3 ILCs and controls
      intestinal immunity and inflammation.
AB  - Unlike adaptive immune cells that require antigen recognition and functional
      maturation during infection, innate lymphoid cells (ILCs) usually respond to
      pathogens promptly and serve as the first line of defense in infectious diseases.
      RAR-related orphan receptor (RORgammat)+ group 3 ILCs are one of the innate cell
      populations that have recently been intensively studied. During the fetal stage
      of development, RORgammat+ group 3 ILCs (e.g., lymphoid tissue inducer cells) are
      required for lymphoid organogenesis. In adult mice, RORgammat+ group 3 ILCs are
      abundantly present in the gut to exert immune defensive functions. Under certain
      circumstances, however, RORgammat+ group 3 ILCs can be pathogenic and contribute
      to intestinal inflammation. Aryl hydrocarbon receptor (Ahr), a ligand-dependent
      transcriptional factor, is widely expressed by various immune and non-immune
      cells. In the gut, the ligand for Ahr can be derived/generated from diet,
      microflora, and/or host cells. Ahr has been shown to regulate different cell
      populations in the immune system including RORgammat+ group 3 ILCs, T helper
      (Th)17/22 cells, gammadeltaT cells, regulatory T cells (Tregs), Tr1 cells, and
      antigen presenting cells. In this review, we will focus on the development and
      function of RORgammat+ group 3 ILCs, and discuss the role of Ahr in intestinal
      immunity and inflammation in mice and in humans. A better understanding of the
      function of Ahr in the gut is important for developing new therapeutic means to
      target Ahr in future treatment of infectious and autoimmune diseases.

PMID- 23975389
TI  - Modeling mass transfer from carmustine-loaded polymeric implants for malignant
      gliomas.
AB  - Significant advances in the encapsulation and release of drugs from degradable
      polymers have led to the Food and Drug Administration approval of Gliadel wafers
      for controlled local delivery of the chemotherapeutic drug carmustine to high
      grade gliomas following surgical resection. Due to the localized nature of the
      delivery method, no pharmacokinetic measurements have been taken in humans.
      Rather, pharmacokinetic studies in animals and associated modeling have indicated
      the capability of carmustine to be delivered in high concentrations within
      millimeters from the implant site over approximately 5 days. Mathematical models
      have indicated that diffusion has a primary role in transport, which may be
      complemented by enhanced fluid convection from postsurgical edema in the initial
      3 days following implantation. Carmustine's penetration distance is also
      presumably limited by its lipophilicity and permeability in the capillaries. This
      review discusses the mathematical models that have been used to predict the
      release and distribution of carmustine from a polymeric implant. These models
      provide a theoretical framework for greater understanding of systems for
      localized drug delivery while highlighting factors that should be considered in
      clinical applications. In effect, Gliadel wafers and similar drug delivery
      implants can be optimized with reduction in required time and resources with such
      a quantitative and integrative approach. 

PMID- 23975390
TI  - Association between in-hospital acute hypertensive episodes and outcomes in older
      trauma patients.
AB  - Although chronic hypertension is associated with long-term complications, few
      studies directly examine the effects of in-hospital acute hypertensive episodes
      in trauma patients. The aim was to determine whether there is an association
      between in-hospital acute hypertension and morbidity. We included trauma patients
      between 45 and 89 years who presented to a level I trauma center between January
      and September 2008. Patients were classified as either experiencing or not
      experiencing acute hypertensive episode(s) as defined by systolic blood pressure
      >=180, or diastolic blood pressure >=110 mmHg, or at least two readings of
      systolic blood pressure >=160 or diastolic blood pressure >=100 mmHg. The primary
      outcome was a composite endpoint of myocardial infarction, stroke, venous
      thromboembolism, new-onset atrial fibrillation, or acute kidney injury. At least
      one acute hypertensive episode occurred in 42.6% (69/162) of patients. A total of
      10.5% patients developed the composite endpoint, 17.4% in the acute hypertensive
      episode group compared to 5.4% in the non-hypertensive group, p = 0.012. Patients
      in the acute hypertensive group were more likely to require an intensive care
      unit admission compared to the non-hypertensive group (33.3 versus 14.0%, p =
      0.004). Of the 17 patients who developed an acute hypertensive episode and met
      the primary endpoint, 10 were on home antihypertensive medications. Of those,
      four were restarted on all medications initially, three on some, two were started
      on new medications, and one was not resumed on home medications. Development of
      acute hypertensive episode(s) in older trauma patients was associated with an
      increase in the composite endpoint. Prospective studies are needed.

PMID- 23975391
TI  - Italian guidelines on thrombolysis indications in ischemic stroke have been
      revised after IST-3 trial and Cochrane revision: cons.

PMID- 23975392
TI  - Italian guidelines on thrombolysis indications in ischaemic stroke have been
      revised after IST 3 trial and Cochrane Review: PROS.

PMID- 23975393
TI  - Modeling study of dose-response relationships for radiation-induced chromosomal
      instability.

PMID- 23975394
TI  - A dynamic model of the immune response to the onset of a tumor.

PMID- 23975395
TI  - Pharmacological and physicochemical properties of mechanochemically synthesized
      supramolecular complexes of acetylsalicylic acid and polysaccharide
      arabinogalactan from larches Larix sibirica and Larix gmelinii.

PMID- 23975396
TI  - Differences in fatty acid composition of cladocerans and copepods from cold and
      warm lakes.

PMID- 23975397
TI  - Physicochemical characterization of uridine phosphorylase from Shewanella
      oneidensis MR-1.

PMID- 23975398
TI  - Radiation-induced chromosomal instability under constrained growth of irradiated
      cells.

PMID- 23975399
TI  - Direct transition of pGA482:ipt plasmid bearing the cytokinin biosynthesis gene
      into the cells of phototrophic purple bacteria Rhodobacter sphaeroides and
      Rhodopseudomonas palustris by electroporation.

PMID- 23975400
TI  - Analysis of insulator proteins binding in reporter genetic constructs transfected
      into Drosophila S2 cells.

PMID- 23975401
TI  - Kinetics and mechanism of inhibition of serine esterases by fluorinated
      carbethoxy 1-aminophosphonates.

PMID- 23975402
TI  - Nerve growth factor suppresses Ehrlich carcinoma growth.

PMID- 23975403
TI  - N,N-disubstituted 2-aminothiazolines as new inhibitors of serine esterases.

PMID- 23975404
TI  - Brain-derived neurotrophic factor loop 4 dipeptide mimetic GSB-106 activates
      TrkB, Erk, and Akt and promotes neuronal survival in vitro.

PMID- 23975405
TI  - Zitramin-a new antidote for acute ethanol intoxication.

PMID- 23975406
TI  - The influence of prolonged streptozotocin diabetes on the thyroid gland function
      in rats.

PMID- 23975407
TI  - Nonenzymatic test system for noninstrumental determination of antibodies to
      species-specific fibers of Yersinia pseudotuberculosis on the basis of nanosized
      carbon particles.

PMID- 23975408
TI  - A comparison among four tract dilation methods of percutaneous nephrolithotomy: a
      systematic review and meta-analysis.
AB  - The purpose of this study was to evaluate the efficacy and safety of the Amplatz
      dilation (AD), metal telescopic dilation (MTD), balloon dilation (BD), and one
      shot dilation (OSD) methods for tract dilation during percutaneous
      nephrolithotomy (PCNL). Relevant eligible studies were identified using three
      electronic databases (Medline, EMBASE, and Cochrane CENTRAL). Database
      acquisition and quality evaluation were independently performed by two reviewers.
      Efficacy (stone-free rate, surgical duration, and tract dilatation fluoroscopy
      time) and safety (transfusion rate and hemoglobin decrease) were evaluated using
      Review Manager 5.2. Four randomized controlled trials and eight clinical
      controlled trials involving 6,820 patients met the inclusion criteria. The pooled
      result from a meta-analysis showed statistically significant differences in tract
      dilatation fluoroscopy time and hemoglobin decrease between the OSD and MTD
      groups, which showed comparable stone-free and transfusion rates. Significant
      differences in transfusion rate were found between the BD and MTD groups. Among
      patients without previous open renal surgery, those who underwent BD exhibited a
      lower blood transfusion rate and a shorter surgical duration compared with those
      who underwent AD. The OSD technique is safer and more efficient than the MTD
      technique for tract dilation during PCNL, particularly in patients with previous
      open renal surgery, resulting in a shorter tract dilatation fluoroscopy time and
      a lesser decrease in hemoglobin. The efficacy and safety of BD are better than AD
      in patients without previous open renal surgery. The OSD technique should be
      considered for most patients who undergo PCNL therapy. 

PMID- 23975409
TI  - Congenital megalourethra presenting with large cystic mass in the inguinal area.
AB  - Congenital megalourethra is a rare urogenital malformation characterized by
      severe dilatation and elongation of the penile urethra. It causes functional
      obstruction of the lower urinary system. Herein, we present a newborn with
      congenital megalourethra with single umbilical artery. 

PMID- 23975410
TI  - Ophthalmological assessment of children with neurofibromatosis type 1.

PMID- 23975411
TI  - Reply to correspondence letter 'Ophthalmological assessment of children with
      neurofibromatosis type 1'.

PMID- 23975412
TI  - Association of trisomy 18 with hepatoblastoma and its implications.
AB  - Hepatoblastoma is a highly malignant embryonal liver tumor that occurs almost
      exclusively in infants and toddlers. Trisomy 18 is the second most common
      autosomal trisomy after trisomy 21 and is generally considered a lethal disorder.
      Ten cases of hepatoblastoma in children with trisomy 18 have been published to
      date. Here, we report on two female patients with trisomy 18 and pretreatment
      extent of disease (PRETEXT) stage 1 hepatoblastoma, which support the presence of
      a nonrandom association between hepatoblastoma and trisomy 18. Both patients
      underwent primary surgical resection without any neoadjuvant or adjuvant
      chemotherapy. The histologies returned as pure fetal epithelial type, and
      combined fetal and embryonal epithelial type. There was no evidence of recurrence
      on serial abdominal ultrasound and serum alpha-fetoprotein levels on follow-up.
      CONCLUSION: Primary surgical resection is a treatment approach that can be
      considered in children with trisomy 18 and PRETEXT stage 1 tumor. However, in
      view of the overall prognosis for trisomy 18, the decision on the optimal
      treatment is a delicate one and has to be individualized in the context of the
      best interests of the child.

PMID- 23975413
TI  - Fifteen-minute consultation: The child with acute ataxia.
AB  - Acute ataxia is a relatively common presentation to the paediatric acute services
      or child neurologist. Although the cause of ataxia is most often benign, it is
      important during initial assessment to recognise or exclude serious causes
      including brain tumour and central nervous system infections. It is equally
      important to recognise the non-neurological causes of unsteady gait and to avoid
      unnecessary investigations. In this review, we have presented a diagnostic
      approach to a child presenting with acute ataxia and described various causes,
      their treatments and outcomes.

PMID- 23975414
TI  - How and when to refer a child for specialist paediatric palliative care.
AB  - Specialist paediatric palliative care is a relatively new area of paediatrics,
      and the interface with other disciplines can occasionally pose challenges for
      referrers due to lack of information about the diverse services available.
      Although services vary on a regional basis, there are common principles which may
      be used to guide and support referrals. Children may be referred to palliative
      care services via a number of routes from community-based primary care to
      regional tertiary centres. Identifying those most likely to benefit from the
      finite resources available can be a challenge, and healthcare professional's
      negative attitudes to palliative care have been further identified as a
      potentially modifiable barrier. This article aims to clarify the role of
      specialist paediatric palliative care, identify who should be eligible for such
      care, describe the services available (including those from children's hospices)
      and provide a tool for assessing some of the most challenging referrals. Many of
      the documents referenced can be downloaded from the Together for Short Lives
      website, and in many cases, there is no charge.

PMID- 23975415
TI  - Laryngeal myxoma: a case report and review of the literature.
AB  - Myxomas are a rare benign neoplasm of uncertain mesenchymal cell origin,
      typically involving the heart. Laryngeal myxomas are uncommon, and are usually
      misdiagnosed as laryngeal polyp. To the best of our knowledge, there are only
      nine reported cases in the English literature. We report a case of a laryngeal
      myxoma presenting clinically as a left vocal cord polyp in a 77 year old male,
      and review the literature related to this rare entity.

PMID- 23975416
TI  - Assessing rumination in response to illness: the development and validation of
      the Multidimensional Rumination in Illness Scale (MRIS).
AB  - The cognitive style of rumination extends existing cognitive models of emotional
      response to illness. In the absence of a specific measure, we developed the
      Multidimensional Rumination in Illness Scale (MRIS). In Study 1, an initial 60
      item pool was tested, followed by confirmation of the factor structure in Study
      2. In Study 1 participants (n = 185) completed the pilot version of the MRIS,
      then in Study 2 (n = 163) a reduced 41-item model was tested. Study 1:
      Exploratory factor analysis of a reduced 32-item scale indicated an initial four
      factor solution for the MRIS (Intrusion, Brooding, Instrumental, Preventability),
      with satisfactory internal consistency and stable factor structure across gender.
      Study 2: Following scale revision, confirmatory factor analysis substantiated the
      adequacy of a three-factor MRIS structure, and good internal consistency, test
      rest reliability, and concurrent and discriminant validity was demonstrated for
      the MRIS. The MRIS exhibited good psychometric properties in the current sample,
      providing a comprehensive assessment of the cognitive style of rumination in the
      context of physical illness. 

PMID- 23975419
TI  - The composite anterolateral thigh flap for knee extensor and skin reconstruction.
AB  - The simultaneous reconstruction of a skin defect and lost extensor mechanism of
      the knee joint is difficult. We present a 31-year-old male who lost the patella
      and had a 9 * 10 cm skin defect after a total patellectomy for an infected open
      patellar fracture. A composite anterolateral thigh (ALT) flap including
      vascularized skin and fascia lata (FL) was elevated. The FL was folded and
      sutured to the remaining patellar tendon. The skin flap covered the skin defect.
      The wound healed uneventfully. Thirty months later, the active range of motion of
      the knee joint was 0 degrees -120 degrees  and the extension strength of the knee
      joint was normal. He could stand on his right leg and walk without assistance.
      The composite ALT flap is a valuable option in knee reconstruction after a total
      patellectomy.

PMID- 23975417
TI  - The effect of widowhood on husbands' and wives' physical activity: the
      Cardiovascular Health Study.
AB  - This prospective study examined the effect of widowhood on physical activity by
      comparing widowed elders to health status-, age-, and sex-matched married
      controls. Participants included 396 married controls and 396 widows/widowers age
      64-91 (M age = 72.7 years) who experienced the death of their spouse while
      participating in the Cardiovascular Health Study. Compared to married controls,
      widowed men, but not women, were more likely to increase their physical activity
      following the death of their spouse. However, this increased level of activity
      was not sustained and declines as time since spousal death passes. Moreover,
      during the year before spousal death, soon-to-be widowed men, but not women,
      increase their physical activity. Our results suggest that widowed men experience
      significant changes in physical activity and that the transition to widowhood
      contribute to these changes. 

PMID- 23975421
TI  - TNF-alpha/TNFR1 signaling promotes gastric tumorigenesis through induction of
      Noxo1 and Gna14 in tumor cells.
AB  - Helicobacter pylori infection induces chronic inflammation that contributes to
      gastric tumorigenesis. Tumor necrosis factor (TNF-alpha) is a proinflammatory
      cytokine, and polymorphism in the TNF-alpha gene increases the risk of gastric
      cancer. We herein investigated the role of TNF-alpha in gastric tumorigenesis
      using Gan mouse model, which recapitulates human gastric cancer development. We
      crossed Gan mice with TNF-alpha (Tnf) or TNF-alpha receptor TNFR1 (Tnfrsf1a)
      knockout mice to generate Tnf-/- Gan and Tnfrsf1a-/- Gan mice, respectively, and
      examined their tumor phenotypes. Notably, both Tnf-/- Gan mice and Tnfrsf1a-/-
      Gan mice showed similar, significant suppression of gastric tumor growth compared
      with control Tnf+/+ or Tnfrsf1a+/+ Gan mice. These results indicate that TNF
      alpha signaling through TNFR1 is important for gastric tumor development. Bone
      marrow (BM) transplantation experiments showed that TNF-alpha expressed by BM
      derived cells (BMDCs) stimulates the TNFR1 on BMDCs by an autocrine or paracrine
      manner, which is important for gastric tumor promotion. Moreover, the microarray
      analysis and colony formation assay indicated that NADPH oxidase organizer 1
      (Noxo1) and Gna14 are induced in tumor epithelial cells in a TNF-alpha-dependent
      manner, and have an important role in tumorigenicity and tumor-initiating cell
      property of gastric cancer cells. Accordingly, it is possible that the activation
      of TNF-alpha/TNFR1 signaling in the tumor microenvironment promotes gastric tumor
      development through induction of Noxo1 and Gna14, which contribute to maintaining
      the tumor cells in an undifferentiated state. The present results indicate that
      targeting the TNF-alpha/TNFR1 pathway may be an effective preventive or
      therapeutic strategy for gastric cancer.

PMID- 23975422
TI  - IBP regulates epithelial-to-mesenchymal transition and the motility of breast
      cancer cells via Rac1, RhoA and Cdc42 signaling pathways.
AB  - Epithelial-to-mesenchymal transition (EMT) is a crucial process for the invasion
      and metastasis of epithelial tumors. However, the molecular mechanisms underlying
      this transition are poorly understood. In this study, we demonstrate that
      interferon regulatory factor 4 binding protein (IBP) regulates EMT and the
      motility of breast cancer cells through Rac1, RhoA and Cdc42 signaling pathways.
      We found that increased expression of IBP was associated with the progression of
      breast cancer and that IBP protein levels were significantly elevated in matched
      distant metastases. High IBP levels also predict shorter overall survival of
      breast cancer patients. Furthermore, the forced expression of IBP decreased the
      expression of the epithelial marker E-cadherin but increased the mesenchymal
      markers in breast cancer cells. In contrast, silencing IBP in metastatic breast
      tumor cells promoted a shift toward an epithelial morphology concomitant with
      increased expression of E-cadherin and decreased expression of mesenchymal
      markers. IBP silencing also reduced the expression of EMT-inducing transcription
      factors (Snail, Slug, ZEB1 and ZEB2). Moreover, we identified a role for IBP in
      endogenous EMT induced by epidermal growth factor (EGF) and deletion of IBP
      attenuated EGF receptor (EGFR) signaling in breast cancer cells. Furthermore, IBP
      regulates the migration, invasion and matrix metalloprotease production in breast
      cancer cells as well as actin cytoskeleton rearrangement and the activation of
      GTP-Rac1, GTP-RhoA and GTP-Cdc42. Taken together, our findings demonstrate an
      oncogenic property for IBP in promoting the metastatic potential of breast cancer
      cells. 

PMID- 23975423
TI  - Overexpression and promoter mutation of the TERT gene in malignant pleural
      mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is a very aggressive tumor with no known
      curative treatment. Better knowledge of the molecular mechanisms of mesothelial
      carcinogenesis is required to develop new therapeutic strategies. MPM, like all
      cancer cells, needs to maintain telomere length to prevent senescence. Previous
      studies suggested that the telomere lengthening mechanism in MPM is based mainly
      on telomerase activity. For this reason, we focused on the key catalytic enzyme,
      TERT (telomerase reverse transcriptase), by analyzing its gene expression in MPM
      and by studying the mechanism underlying its upregulation. We used our large
      collection of MPM composed of 61 MPM in culture and 71 frozen MPM tumor samples.
      Evaluation of TERT mRNA expression by quantitative RT-PCR showed overexpression
      in MPM in culture compared with normal mesothelial cells, and in MPM tumor
      samples compared with normal pleura. We identified a 'hot spot' of mutations in
      the TERT gene core promoter in both MPM in culture and in MPM tumor samples with
      an overall frequency of 15%. Furthermore, data clearly identified mutation in the
      TERT promoter as a mechanism of TERT mRNA upregulation in MPM. In contrast, gene
      copy number amplification was not associated with TERT overexpression. Then, we
      analyzed the clinicopathological, etiological and genetic characteristics of MPM
      with mutations in the TERT promoter. TERT promoter mutations were more frequent
      in MPM with sarcomatoid histologic subtype (P<0.01), and they were frequently
      associated with CDKN2A gene inactivation (P=0.03). In conclusion, a subgroup of
      MPM presents TERT promoter mutations, which lead to TERT mRNA upregulation. This
      is the first recurrent gain-of-function oncogenic mutations identified in MPM. 

PMID- 23975424
TI  - Par-4/THAP1 complex and Notch3 competitively regulated pre-mRNA splicing of CCAR1
      and affected inversely the survival of T-cell acute lymphoblastic leukemia cells.
AB  - Although the intensification of therapy for children with T-cell acute
      lymphoblastic leukemia (T-ALL) has substantially improved clinical outcomes, T
      ALL remains an important challenge in pediatric oncology. Here, we report that
      the cooperative synergy between prostate apoptosis response factor-4 (Par-4) and
      THAP1 induces cell cycle and apoptosis regulator 1 (CCAR1) gene expression and
      cellular apoptosis in human T-ALL cell line Jurkat cells, CEM cells and primary
      cultured neoplastic T lymphocytes from children with T-ALL. Par-4 and THAP1
      collaborated to activate the promoter of CCAR1 gene. Mechanistic investigations
      revealed that Par-4 and THAP1 formed a protein complex by the interaction of
      their carboxyl termini, and THAP1 bound to CCAR1 promoter though its zinc
      dependent DNA-binding domain at amino terminus. Par-4/THAP1 complex and Notch3
      competitively bound to CCAR1 promoter and competitively modulated alternative pre
      mRNA splicing of CCAR1, which resulted in two different transcripts and played an
      opposite role in T-ALL cell survival. Despite Notch3 induced a shift splicing
      from the full-length isoform toward a shorter form of CCAR1 mRNA by splicing
      factor SRp40 and SRp55, Par-4/THAP1 complex strongly antagonized this inductive
      effect. Our finding revealed a mechanistic rationale for Par-4/THAP1-induced
      apoptosis in T-ALL cells that would be of benefit to develop a new therapy
      strategy for T-ALL. 

PMID- 23975426
TI  - Preclinical modeling of EGFR-specific antibody resistance: oncogenic and immune
      associated escape mechanisms.
AB  - To define the molecular basis of secondary resistance to epidermal growth factor
      receptor (EGFR)-specific antibodies is crucial to increase clinical benefit in
      patients. The limited access to posttreatment tumor samples constitutes the major
      barrier to conduct these studies, representing preclinical experimentation as a
      useful alternative. Anti-EGFR antibody-based therapy has been reported to mediate
      tumor regression by interrupting oncogenic signals and, more recently, by
      inducing antitumor immunological responses. However, resistance models have been
      focused only on tumor escape associated with EGFR blockade, whereas studies
      describing immune-associated escape mechanisms have not been reported thus far.
      To address this idea, we modeled resistance induction in D122 metastasis-bearing
      C57BL/6 mice treated with 7A7 (an anti-murine EGFR antibody). Similarly to
      patients receiving EGFR-specific antibodies, 7A7 resistance promotion represents
      an important drawback to successful therapy. Characterization of primary cultures
      derived from metastasis in 7A7-treated mice revealed a high frequency of tumor
      variants resistant to in vivo and in vitro antibody treatment. We showed, for the
      first time, the convergence of alterations in oncogenic and immunological
      pathways in 7A7-resistant variants. To identify key molecules behind resistance,
      seven 7A7-resistant variants were screened. HER3 overexpression and PTEN
      deficiency leading to hyperactivation of protumoral downstream signaling were
      found in these variants as a consequence of 7A7-mediated EGFR inhibition.
      Concomitantly, we found a high percentage of resistant variants carrying
      abnormalities in the constitutive and/or interferon gamma (IFN-gamma)-inducible
      major histocompatibility complex I (MHC-I) expression. A significant decrease in
      mRNA levels for MHC-I heavy chains, beta2-microglogulin and antigen processing
      machinery genes as well as transcriptional alterations in IFN-gamma pathway
      components were identified as the main mechanisms underlying MHC-I expression
      defects in 7A7-resistant variants. Notably, these defects have not been
      previously associated with EGFR-specific antibody resistance, providing novel
      immunological escape mechanisms. This study has strong implications for the
      development of new combination strategies to overcome anti-EGFR antibodies
      refractoriness. 

PMID- 23975427
TI  - NF-kappaB-mediated transcriptional upregulation of TNFAIP2 by the Epstein-Barr
      virus oncoprotein, LMP1, promotes cell motility in nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC), which is closely associated with Epstein-Barr
      virus (EBV), is a metastasis-prone epithelial cancer. We previously showed that
      tumor necrosis factor alpha-induced protein 2 (TNFAIP2) is highly expressed in
      NPC tumor tissues and is correlated with metastasis and poor survival in NPC
      patients. However, the underlying mechanism remains unclear. In this study, we
      demonstrate that the EBV oncoprotein, latent membrane protein 1 (LMP1), can
      transcriptionally induce TNFAIP2 expression via NF-kappaB. Quantitative RT-PCR
      and western blotting revealed that LMP1 induces TNFAIP2 expression through its C
      terminal-activating region (CTAR2) domain, which is required for transduction of
      NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells)
      signaling. Inhibition of NF-kappaB activation or depletion of p65 (a component of
      NF-kappaB) by RNA interference abolished the LMP1-induced expression of TNFAIP2,
      whereas ectopic expression of p65 was sufficient to induce TNFAIP2 expression.
      Luciferase reporter assays showed that LMP1 transcriptionally induces TNFAIP2
      expression through a newly identified NF-kappaB-binding site within the TNFAIP2
      promoter (-3,869 to -3,860 bp). Immunohistochemical analysis of NPC biopsy
      specimens further revealed a significant correlation between the protein levels
      of TNFAIP2 and activated p65 (R=0.689, P<0.001), indicating that our findings are
      clinically relevant. Immunofluorescence microscopy and co-immunoprecipitation
      assays showed that TNFAIP2 associates with actin and is involved in the formation
      of actin-based membrane protrusions. Furthermore, transwell migration assays
      demonstrated that TNFAIP2 contributes to LMP1-induced cell motility.
      Collectively, these findings provide novel insights into the regulation of
      TNFAIP2 and its role in promoting NPC tumor progression.

PMID- 23975425
TI  - N-cadherin/FGFR promotes metastasis through epithelial-to-mesenchymal transition
      and stem/progenitor cell-like properties.
AB  - N-cadherin and HER2/neu were found to be co-expressed in invasive breast
      carcinomas. To test the contribution of N-cadherin and HER2 in mammary tumor
      metastasis, we targeted N-cadherin expression in the mammary epithelium of the
      MMTV-Neu mouse. In the context of ErbB2/Neu, N-cadherin stimulated carcinoma cell
      invasion, proliferation and metastasis. N-cadherin caused fibroblast growth
      factor receptor (FGFR) upmodulation, resulting in epithelial-to-mesenchymal
      transition (EMT) and stem/progenitor like properties, involving Snail and Slug
      upregulation, mammosphere formation and aldehyde dehydrogenase activity. N
      cadherin potentiation of the FGFR stimulated extracellular signal regulated
      kinase (ERK) and protein kinase B (AKT) phosphorylation resulting in differential
      effects on metastasis. Although ERK inhibition suppressed cyclin D1 expression,
      cell proliferation and stem/progenitor cell properties, it did not affect
      invasion or EMT. Conversely, AKT inhibition suppressed invasion through Akt 2
      attenuation, and EMT through Snail inhibition, but had no effect on cyclin D1
      expression, cell proliferation or mammosphere formation. These findings suggest N
      cadherin/FGFR has a pivotal role in promoting metastasis through differential
      regulation of ERK and AKT, and underscore the potential for targeting the FGFR in
      advanced ErbB2-amplified breast tumors. 

PMID- 23975428
TI  - RKIP and HMGA2 regulate breast tumor survival and metastasis through lysyl
      oxidase and syndecan-2.
AB  - Elucidating targets of physiological tumor metastasis suppressors can highlight
      key signaling pathways leading to invasion and metastasis. To identify downstream
      targets of the metastasis suppressor Raf-1 kinase inhibitory protein
      (RKIP/PEBP1), we utilized an integrated approach based upon statistical analysis
      of tumor gene expression data combined with experimental validation. Previous
      studies from our laboratory identified the architectural transcription factor and
      oncogene, high mobility group AT-hook 2 (HMGA2), as a target of inhibition by
      RKIP. Here we identify two signaling pathways that promote HMGA2-driven
      metastasis. Using both human breast tumor cells and an MMTV-Wnt mouse breast
      tumor model, we show that RKIP induces and HMGA2 inhibits expression of miR-200b;
      miR-200b directly inhibits expression of lysyl oxidase (LOX), leading to
      decreased invasion. RKIP also inhibits syndecan-2 (SDC2), which is aberrantly
      expressed in breast cancer, via downregulation of HMGA2; but this mechanism is
      independent of miR-200. Depletion of SDC2 induces apoptosis and suppresses breast
      tumor growth and metastasis in mouse xenografts. RKIP, LOX and SDC2 are
      coordinately regulated and collectively encompass a prognostic signature for
      metastasis-free survival in ER-negative breast cancer patients. Taken together,
      our findings reveal two novel signaling pathways targeted by the metastasis
      suppressor RKIP that regulate remodeling of the extracellular matrix and tumor
      survival. 

PMID- 23975429
TI  - Ebp1 activates podoplanin expression and contributes to oral tumorigenesis.
AB  - Podoplanin is highly expressed in human cancers. However, mechanisms regulating
      podoplanin expression remain elusive. Here we show that podoplanin promotes
      tumorigenesis of oral squamous cell carcinoma (OSCC) and precancerous cells both
      in vitro and in vivo, and the ErbB3-binding protein-1 (Ebp1) can be activated in
      oral tumorigenesis and can serve as a transcriptional activator to drive
      podoplanin expression in the malignant progression. Most of the OSCC cell lines
      have no detectable podoplanin protein in low-density cultures. However, the
      protein becomes detectable in high-density cultures and is required for in-vivo
      tumor formation of OSCC and oral premalignancies. In a high-density culture
      condition, podoplanin expression can be triggered at both mRNA and protein
      levels. In this condition, we showed that Ebp1 is upregulated, translocated from
      the cytoplasm to the nucleus and binds to the podoplanin promoter to result in a
      dramatic increase of podoplanin mRNA and protein. Ebp1 downregulation
      significantly reduced podoplanin expression levels in OSCC cells with a decreased
      anchorage-dependent growth, invasion and wound healing. Conversely, Ebp1
      overexpression enhanced these malignant features through podoplanin upregulation
      both in vitro and in vivo. In 81 patients with oral premalignant lesions, we
      found that Ebp1 expression is strongly related to OSCC development. We conclude
      that Ebp1 has a key role in the upregulation of podoplanin and may contribute to
      oral tumorigenesis.

PMID- 23975430
TI  - Significance of PELP1/HDAC2/miR-200 regulatory network in EMT and metastasis of
      breast cancer.
AB  - Tumor metastasis is the leading cause of death among breast cancer patients.
      PELP1 (proline, glutamic acid and leucine rich protein 1) is a nuclear receptor
      coregulator that is upregulated during breast cancer progression to metastasis
      and is an independent prognostic predictor of shorter survival of breast cancer
      patients. Here, we show that PELP1 modulates expression of metastasis-influencing
      microRNAs (miRs) to promote cancer metastasis. Whole genome miR array analysis
      using PELP1-overexpressing and PELP1-underexpressing model cells revealed that
      miR-200 and miR-141 levels inversely correlated with PELP1 expression. Consistent
      with this, PELP1 knockdown resulted in lower expression of miR-200a target genes
      ZEB1 and ZEB2. PELP1 knockdown significantly reduced tumor growth and metastasis
      compared with parental cells in an orthotopic xenograft tumor model. Furthermore,
      re-introduction of miR-200a and miR-141 mimetics into PELP1-overexpressing cells
      reversed PELP1 target gene expression, decreased PELP1-driven migration/invasion
      in vitro and significantly reduced in vivo metastatic potential in a preclinical
      model of experimental metastasis. Our results demonstrated that PELP1 binds to
      miR-200a and miR-141 promoters and regulates their expression by recruiting
      chromatin modifier histone deacetylase 2 (HDAC2) as revealed by chromatin
      immunoprecipitation, small interfering RNA and HDAC inhibitor assays. Taken
      together, our results suggest that PELP1 regulates tumor metastasis by
      controlling the expression and functions of the tumor metastasis suppressors miR
      200a and miR-141. 

PMID- 23975431
TI  - Signaling mediated by the NF-kappaB sub-units NF-kappaB1, NF-kappaB2 and c-Rel
      differentially regulate Helicobacter felis-induced gastric carcinogenesis in
      C57BL/6 mice.
AB  - The classical nuclear factor-kappaB (NF-kappaB) signaling pathway has been shown
      to be important in a number of models of inflammation-associated cancer. In a
      mouse model of Helicobacter-induced gastric cancer, impairment of classical NF
      kappaB signaling in the gastric epithelium led to the development of increased
      preneoplastic pathology, however the role of specific NF-kappaB proteins in
      Helicobacter-associated gastric cancer development remains poorly understood. To
      investigate this C57BL/6, Nfkb1(-/-), Nfkb2(-/-) and c-Rel(-/-) mice were
      infected with Helicobacter felis for 6 weeks or 12 months. Bacterial
      colonization, gastric atrophy and preneoplastic changes were assessed
      histologically and cytokine expression was assessed by qPCR. Nfkb1(-/-) mice
      developed spontaneous gastric atrophy when maintained for 12 months in
      conventional animal house conditions. They also developed more pronounced gastric
      atrophy after short-term H. felis colonization with a similar extent of
      preneoplasia to wild-type (WT) mice after 12 months. c-Rel(-/-) mice developed a
      similar degree of gastric atrophy to WT mice; 3 of 6 of these animals also
      developed lymphoproliferative lesions after 12 months of infection. Nfkb2(-/-)
      mice developed minimal gastric epithelial pathology even 12 months after H. felis
      infection. These findings demonstrate that NF-kappaB1- and NF-kappaB2-mediated
      signaling pathways differentially regulate the epithelial consequences of H.
      felis infection in the stomach, while c-Rel-mediated signaling also appears to
      modulate the risk of lymphomagenesis in gastric mucosa-associated lymphoid
      tissue. 

PMID- 23975432
TI  - The role of KCNQ1 in mouse and human gastrointestinal cancers.
AB  - Kcnq1, which encodes for the pore-forming alpha-subunit of a voltage-gated
      potassium channel, was identified as a gastrointestinal (GI) tract cancer
      susceptibility gene in multiple Sleeping Beauty DNA transposon-based forward
      genetic screens in mice. To confirm that Kcnq1 has a functional role in GI tract
      cancer, we created Apc(Min) mice that carried a targeted deletion mutation in
      Kcnq1. Results demonstrated that Kcnq1 is a tumor suppressor gene as Kcnq1 mutant
      mice developed significantly more intestinal tumors, especially in the proximal
      small intestine and colon, and some of these tumors progressed to become
      aggressive adenocarcinomas. Gross tissue abnormalities were also observed in the
      rectum, pancreas and stomach. Colon organoid formation was significantly
      increased in organoids created from Kcnq1 mutant mice compared with wild-type
      littermate controls, suggesting a role for Kcnq1 in the regulation of the
      intestinal crypt stem cell compartment. To identify gene expression changes due
      to loss of Kcnq1, we carried out microarray studies in the colon and proximal
      small intestine. We identified altered genes involved in innate immune responses,
      goblet and Paneth cell function, ion channels, intestinal stem cells, epidermal
      growth factor receptor and other growth regulatory signaling pathways. We also
      found genes implicated in inflammation and in cellular detoxification. Pathway
      analysis using Ingenuity Pathway Analysis and Gene Set Enrichment Analysis
      confirmed the importance of these gene clusters and further identified
      significant overlap with genes regulated by MUC2 and CFTR, two important
      regulators of intestinal homeostasis. To investigate the role of KCNQ1 in human
      colorectal cancer (CRC), we measured protein levels of KCNQ1 by
      immunohistochemistry in tissue microarrays containing samples from CRC patients
      with liver metastases who had undergone hepatic resection. Results showed that
      low expression of KCNQ1 expression was significantly associated with poor overall
      survival.

PMID- 23975434
TI  - Aberrantly activated AREG-EGFR signaling is required for the growth and survival
      of CRTC1-MAML2 fusion-positive mucoepidermoid carcinoma cells.
AB  - Salivary gland tumors (SGT) are a group of highly heterogeneous head and neck
      malignancies with widely varied clinical outcomes and no standard effective
      treatments. The CRTC1-MAML2 fusion oncogene, encoded by a recurring chromosomal
      translocation t(11;19)(q14-21;p12-13), is a frequent genetic alteration found in
      >50% of mucoepidermoid carcinomas (MEC), the most common malignant SGT. In this
      study, we aimed to define the role of the CRTC1-MAML2 oncogene in the maintenance
      of MEC tumor growth and to investigate critical downstream target genes and
      pathways for therapeutic targeting of MEC. By performing gene expression analyses
      and functional studies via RNA interference and pharmacological modulation, we
      determined the importance of the CRTC1-MAML2 fusion gene and its downstream AREG
      EGFR signaling in human MEC cancer cell growth and survival in vitro and in vivo
      using human MEC xenograft models. We found that CRTC1-MAML2 fusion oncogene was
      required for the growth and survival of fusion-positive human MEC cancer cells in
      vitro and in vivo. The CRTC1-MAML2 oncoprotein induced the upregulation of the
      epidermal growth factor receptor (EGFR) ligand Amphiregulin (AREG) by co
      activating the transcription factor CREB, and AREG subsequently activated EGFR
      signaling in an autocrine manner that promoted MEC cell growth and survival.
      Importantly, CRTC1-MAML2-positive MEC cells were highly sensitive to EGFR
      signaling inhibition. Therefore, our study revealed that aberrantly activated
      AREG-EGFR signaling is required for CRTC1-MAML2-positive MEC cell growth and
      survival, suggesting that EGFR-targeted therapies will benefit patients with
      advanced, unresectable CRTC1-MAML2-positive MEC.

PMID- 23975433
TI  - Role of DNA damage response pathways in preventing carcinogenesis caused by
      intrinsic replication stress.
AB  - Defective DNA replication can result in genomic instability, cancer and
      developmental defects. To understand the roles of DNA damage response (DDR) genes
      on carcinogenesis in mutants defective for core DNA replication components, we
      utilized the Mcm4(Chaos3/Chaos3) ('Chaos3') mouse model that, by virtue of an
      amino-acid alteration in MCM4 that destabilizes the MCM2-7 DNA replicative
      helicase, has fewer dormant replication origins and an increased number of
      stalled replication forks. This leads to genomic instability and cancer in most
      Chaos3 mice. We found that animals doubly mutant for Chaos3 and components of the
      ataxia telangiectasia-mutated (ATM) double-strand break response pathway (Atm,
      p21/Cdkn1a and Chk2/Chek2) had decreased tumor latency and/or increased tumor
      susceptibility. Tumor latency and susceptibility differed between genetic
      backgrounds and genders, with females demonstrating an overall greater cancer
      susceptibility to Atm and p21 deficiency than males. Atm deficiency was
      semilethal in the Chaos3 background and impaired embryonic fibroblast
      proliferation, suggesting that ATM drug inhibitors might be useful against tumors
      with DNA replication defects. Hypomorphism for the 9-1-1 component Hus1 did not
      affect tumor latency or susceptibility in Chaos3 animals, and tumors in these
      mice did not exhibit impaired ATR pathway signaling. These and other data
      indicate that under conditions of systemic replication stress, the ATM pathway is
      particularly important both for cancer suppression and viability during
      development. 

PMID- 23975436
TI  - Answer to the Letter to the Editor of H. Namazi concerning "Denosumab: a
      potential new and innovative treatment option for aneurysmal bone cysts" by Lange
      T, Stehling C, Frohlich B, Klingenhofer M, Kunkel P, Schneppenheim R, Escherich
      G, Gosheger G, Hardes J, Jurgens H, Schulte TL (2013), Eur Spine J;22(6):1417
      1422.

PMID- 23975435
TI  - p53 regulates mesenchymal stem cell-mediated tumor suppression in a tumor
      microenvironment through immune modulation.
AB  - p53 is one of the most studied genes in cancer biology, and mutations in this
      gene may be predictive for the development of many types of cancer in humans and
      in animals. However, whether p53 mutations in non-tumor stromal cells can affect
      tumor development has received very little attention. In this study, we show that
      B16F0 melanoma cells form much larger tumors in p53-deficient mice than in wild
      type mice, indicating a potential role of p53 deficiency in non-tumor cells of
      the microenvironment. As mesenchymal stem cells (MSCs) are attracted to tumors
      and form a major component of the tumor microenvironment, we examined the
      potential role of p53 status in MSCs in tumor development. We found that larger
      tumors resulted when B16F0 melanoma cells were co-injected with bone marrow MSCs
      derived from p53-deficient mice rather than MSCs from wild-type mice.
      Interestingly, this tumor-promoting effect by p53-deficient MSCs was not observed
      in non-obese diabetic/severe combined immunodeficiency mice, indicating the
      immune response has a critical role. Indeed, in the presence of inflammatory
      cytokines, p53-deficient MSCs expressed more inducible nitric oxide synthase
      (iNOS) and exhibited greater immunosuppressive capacity. Importantly, tumor
      promotion by p53-deficient MSCs was abolished by administration of S
      methylisothiourea, an iNOS inhibitor. Therefore, our data demonstrate that p53
      status in tumor stromal cells has a key role in tumor development by modulating
      immune responses.

PMID- 23975437
TI  - Multifidus innervation and muscle assessment post-spinal surgery.
AB  - PURPOSE: Assessment of the integrity of the multifidus muscles and corresponding
      nerve roots, post-open (OSS) versus minimally invasive spinal surgery (MISS) for
      lumbar spine fractures. METHODS: We investigated the first six patients
      undergoing MISS in our institution and age- and sex-matched them with 6 random
      patients who previously had OSS. All had a similar lumbar fracture configuration
      without evidence of spinal cord injury. All were assessed using ultrasound muscle
      quantification and electromyographic studies at a minimum of 6 months post
      operatively. Mean cross-sectional area (CSA) was measured at sequential levels
      within and adjacent to the operative field. Concentric needle electromyography
      was performed at instrumented and adjacent non-instrumented levels in each
      patient. RESULTS: Mean CSA across all lumbar multifidus muscles was 4.29 cm(2) in
      the MISS group, 2.26 cm(2) for OSS (p = 0.08). At the instrumented levels, mean
      CSA was 4.21 cm(2) for MISS and 2.03 cm(2) for OSS (p = 0.12). At non
      instrumented adjacent levels, mean CSA was 4.46 cm(2) in the MISS group, 2.87
      cm(2) for OSS (p = 0.05). Electromyography at non-instrumented adjacent levels
      demonstrated nerve function within normal limits in 5/6 levels in the MISS group
      compared to 1/6 levels in the OSS (p = 0.03). Instrumented levels demonstrated
      nerve function within normal limits in 5/12 levels in the MISS group compared
      with 4/12 in the OSS group, including moderate-severe denervation at 5 levels in
      the OSS group (p = 0.15). CONCLUSIONS: Posterior instrumented MISS demonstrates a
      significantly superior preservation of the medial branch of the posterior ramus
      of the spinal nerve and less muscle atrophy, particularly at adjacent levels when
      compared to OSS.

PMID- 23975438
TI  - Sacral myolipoma with symptomatic contraction of the conus at standing on tiptoe.
AB  - INTRODUCTION: We present a case with spinal myolipoma that was unique in its
      anatomical composition and symptomatology. CASE REPORT: An 18-year-old male
      presented with urinary retention and buttock pain exacerbated by standing on
      tiptoe underwent untethering of the low-set conus associated with a sacral fatty
      tract. Electrical stimulation of the spinal roots beside the upper conus induced
      anomalous caudal movement of the conus and contraction of the gastrocnemius
      muscle. In the lower conus, an ectopic muscle bridging the conus and dura was
      found, and the tissue contracted upon electrical stimulation. The
      histopathological diagnosis was myolipoma involving mature striated muscle and
      fat cells. Postoperatively his buttock pain was relieved immediately, but urinary
      retention persisted. CONCLUSION: We posit that his buttock pain, exacerbated by
      standing on tiptoe, was due to traction of the conus by contraction of the
      ectopic muscle that was aberrantly innervated from the sacral spinal roots.

PMID- 23975440
TI  - Documentation of outcomes for sacroiliac joint fusion: does prior spinal fusion
      influence the outcome?
AB  - PURPOSE: The purpose of this prospective case series (level II) was to determine
      the clinical outcomes of anterior SIJ fusion, comparing the outcomes of patients
      who had prior spinal fusions at any level compared to patients who have not.
      METHODS: This prospective study included 25 patients who underwent SIJ fusion
      with anterior plate fixation. All patients had failed non-operative treatment,
      had a positive Patrick test, and positive response to intra-articular SIJ
      injections with greater than 50 % pain relief. Patients had follow-up at 3, 6, 9
      and 12 months where they completed Oswestry disability index (ODI) and Short
      Musculoskeletal Functional Assessment (SMFA) surveys. Outcome data are available
      for 19 patients who completed pre-operative and 12-month follow-up surveys. Their
      average time of the final follow-up was 1.1 years (range 10-33 months). RESULTS:
      Significant improvements between pre-operative and the final follow-up in ODI (p
      = 0.007) and SMFA (p = 0.01) were observed; the ODI assessed outcomes in patients
      who had previous spinal fusion surgery were significantly worse than those that
      did not at the final follow-up (p = 0.04). CONCLUSION: Patients who have not
      undergone prior spinal fusion surgery, regardless of age, gender, and BMI have
      better outcomes following anterior SIJ fusion.

PMID- 23975439
TI  - Parameters influencing the outcome after total disc replacement at the
      lumbosacral junction. Part 2: distraction and posterior translation lead to
      clinical failure after a mean follow-up of 5 years.
AB  - PURPOSE: The aim of the second part of the study was to investigate the influence
      of parameters that lead to increased facet joint contact or capsule tensile
      forces (disc height, lordosis, and sagittal misalignment) on the clinical outcome
      after total disc replacement (TDR) at the lumbosacral junction. METHODS: A total
      of 40 patients of a prospective cohort study who received TDR because of
      degenerative disc disease or osteochondrosis L5/S1 were invited to an additional
      follow-up for clinical (ODI and VAS for overall, back, and leg pain) and
      radiographic analysis (a change in disc height, lordosis, or sagittal vertebral
      misalignment compared with the preoperative state). Based on the final ODI,
      patients were retrospectively distributed into groups N (normal: <25 %) or F
      (failure >= 25 %) for radiographic parameter comparison. A correlation analysis
      was performed between the clinical and radiological results. RESULTS: A total of
      34 patients were available at a mean follow-up of 59.5 months. Both groups (N =
      24; F = 10 patients) presented a significant improvement in overall pain, back
      pain, and ODI over time. At the final follow-up, higher clinical scores
      correlated with a larger disc height, increased lordosis, and posterior
      translation of the superior vertebra, which was also reflected by significant
      differences in these parameters in the group comparison. CONCLUSIONS: Parameters
      associated with increased facet joint capsule tensile forces lead to an inferior
      clinical outcome at mid-term follow-up. When performing TDR, we therefore suggest
      avoiding iatrogenic posterior translation and overdistraction (and consecutive
      lordosis).

PMID- 23975443
TI  - Computer tomography prototyping and virtual procedure simulation in difficult
      cases of hip replacement surgery.
AB  - Each year approximately 1 million total hip replacements (THR) are performed
      worldwide. A percentage of failure due to surgical approach and imprecise implant
      placement still exists. These result in several serious complications. We propose
      an approach to plan, to simulate, and to assist prosthesis implantation for
      difficult cases of THR based on 3-D virtual models, generated by segmenting
      patients' CT images, 3-D solid models, obtained by rapid prototyping (RP), and
      virtual procedure simulation. We carried out 8 THR with the aid of 3-D
      reconstruction and RP. After each procedure a questionnaire was submitted to the
      surgeon to assess the perceived added value of the technology. In all cases, the
      surgeon evaluated the 3-D model as useful in order to perform the planning. The
      clinical results showed a mean increase in the Harris Hip Score of about 42.5
      points. The mean time of prototyping was 7.3 hours, (min 3.5 hours, max 9.3
      hours). The mean surgery time was 65 minutes (min 50 minutes, max 88 minutes).
      Our study suggests that meticulous preoperative planning is necessary in front of
      a great aberration of the joint and in absence of normal anatomical landmarks, CT
      scan is mandatory, and 3-D reconstruction with solid model is useful. 

PMID- 23975441
TI  - Efficacy and safety of tenecteplase in pulmonary embolism.
AB  - Pulmonary embolism (PE) is a relatively common life-threatening cardiovascular
      condition associated with significant morbidity and mortality. We present the
      efficacy and safety data of weight-adjusted tenecteplase in 30 consecutive
      patients of acute PE. 30 patients (22 male, 8 female) with acute PE were included
      in the study and divided into three groups: (1) Acute PE complicated by shock
      stage and/or persistent hypotension (12 patients). (2) RV dilatation and/or
      dysfunction without hypotension (14 patients). (3) Severe hypoxemia without
      hypotension and RV dysfunction (4 patients). Predominant symptoms were dyspnoea,
      cough, chest pain, syncope and haemoptysis, noted in 100% (30), 40% (12), 54%
      (16), 32% (9) and 10% (3) of patients respectively. RV dilatation and dyskinesia
      were present in 86%, septal paradoxical movement in 73% and inferior venacava
      collapse absent in 53% of patients respectively. 12 patients presented with acute
      PE and cardiogenic shock, 14 patients showed RV dilatation and dysfunction with
      systolic BP >90 mmHg and four patients were having RV dilation without
      dysfunction but severe hypoxemia. There was significant reduction in right
      ventricular systolic pressure and improvement in right ventricular dysfunction.
      Our study shows that tenecteplase is very effective and safe in the treatment of
      PE with minimal risk of bleeding in high risk group and intermediate risk and
      even in selective low risk category group of patients. However, in view of small
      number of patients in study group, a large multicentre randomized study would be
      required to draw a firm conclusion regarding the thrombolysis in low risk
      category patient.

PMID- 23975444
TI  - Mesh fixation compared with nonfixation in transabdominal preperitoneal
      laparoscopic inguinal hernia repair.
AB  - This study was conducted to compare laparoscopic inguinal hernia repair with or
      without mesh fixation regarding recurrence rate and duration of operation time. A
      sample of 73 patients who underwent laparoscopic transabdominal pre-peritoneal
      (TAPP) inguinal hernia repair from January 2002 to January 2010 were derived from
      the medical records of university hospitals including Ekbatan, Beasat, and
      Shaheed Beheshti, as well as private hospitals. MERSILENETM Mesh (Johnson &
      Johnson Medical GmbH, Norderstedt, Germany) fixation was performed for 23 cases
      and polypropylene mesh without fixation for the rest. The recurrence rate was
      followed in both groups for two years. The patients ages were from 7 to 64 years,
      70 patients (95%) were male. Operation time for mesh fixation and nonfixation was
      68.09 and 21.10 minutes, respectively (P < 0.001). Two recurrences occurred in
      the mesh fixation group versus no recurrence in the nonfixation group (P =
      0.096). The results of this study revealed that laparoscopic TAPP inguinal hernia
      repair without mesh fixation is safe and feasible with no increase in recurrence
      rate. In addition, it offers a significantly shorter operation time than TAPP
      mesh fixation. However, we need more evidence based on randomized clinical trials
      to compare the benefits and harm of the two methods.

PMID- 23975445
TI  - Systematic review of screening investigations for peripheral arterial disease in
      patients with diabetes mellitus.
AB  - Diabetes-related foot complications are a major cause of amputation. The presence
      of peripheral arterial disease (PAD) identifies those at increased risk of
      ulceration, failure to heal an ulcer, and amputation. This systematic review
      assesses the ability of noninvasive screening tests to detect PAD in patients
      with diabetes mellitus. A database search was performed using the OVIDSP Web
      site, from 1946 to June 30, 2012 (MEDLINE(r)), and from 1974 to June 30, 2012
      (EMBASE), to identify studies assessing the utility of screening tests in
      detecting PAD or predicting clinical outcomes in patients with diabetes mellitus.
      Thirteen studies were identified that reported sensitivity and specificity data
      on screening tests. No single screening test was reliable in identifying or
      excluding peripheral arterial disease in patients with diabetes. Although the
      evidence base is limited, transcutaneous oxygen measurements appear to be
      predictive of ulcer or surgical wound healing. The diagnosis of PAD (and the
      decision to revascularize) in patients with diabetes is unreliable using
      screening tests. Therefore, all patients with diabetes-related foot ulceration
      should be assessed by a multidisciplinary diabetes foot team that has access to a
      vascular specialist. A low threshold for noninvasive diagnostic imaging seems
      appropriate in patients with diabetes-related foot ulceration. 

PMID- 23975446
TI  - Factors contributing to failure of laparoscopic myomectomy.
AB  - Laparoscopic myomectomy is one of the best treatment options for women with
      symptomatic fibroids who wish to maintain their fertility. Compared with
      myomectomy by laparotomy, the laparoscopic approach is associated with shorter
      hospital stay, faster recovery, less postoperative pain, and reduced adhesion
      formation. Laparoscopic myomectomy is technically challenging, and occasionally
      the procedure needs to be completed by laparotomy. In this review, I will
      describe my team's experience with laparoscopic myomectomy and discuss factors
      contributing to failure. The most important factors affecting conversion of a
      laparoscopic myomectomy to laparotomy are patient selection and the laparoscopic
      expertise of the surgeon. Each surgeon should determine his or her criteria for
      laparoscopic myomectomy. Other factors include posterior intramural location,
      soft consistency associated with the use of gonadotropin releasing hormone
      agonist (GnRHa), the diameter of the dominant myoma, and the weight of the myoma.
      The use of robot-assisted technology may provide a means to overcome the
      challenges encountered with enucleation, extraction, and repair that are seen
      with conventional laparoscopic myomectomy. 

PMID- 23975447
TI  - Does Amicar affect blood loss in patients with adolescent idiopathic scoliosis
      treated with pedicle screws and Ponte osteotomies?
AB  - Amicar may affect estimated blood loss (EBL) and blood transfusion in patients
      with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal fusion
      (PSF) with pedicle screws and Ponte osteotomies. We performed a retrospective
      analysis of a prospectively collected, single-center database of 33 patients with
      main thoracic AIS treated with greater than 80% pedicle screws. Patients were
      divided into two groups based on whether they received Amicar (Yes), or did not
      receive any antifibrinolytics and Ponte osteotomies (No). Demographic,
      radiographic, and intraoperative data were compared between the two groups.
      Seventeen patients were treated with Amicar (Yes) (10 of whom had Ponte
      osteotomies) and 16 patients had neither antifibrinolytics nor Ponte osteotomies
      (No). The two groups had similar preoperative main Cobb angles, major curve
      flexibility, and gender. Despite longer operating times and a majority of
      patients receiving Ponte osteotomies, the Amicar group had a significantly lower
      EBL and homologous blood transfusion rate. Autologous transfusion volume was less
      in the Amicar group and trended toward significance. There were no differences in
      mean arterial pressure during surgery. There were no complications in either
      group. Amicar reduces EBL and homologous transfusion requirements in patients
      with main thoracic AIS undergoing PSF with pedicle screws and Ponte osteotomies. 

PMID- 23975448
TI  - Management of the base of the appendix in pediatric laparoscopic appendectomy:
      clip, ligate, or staple?
AB  - Options for intracorporeal appendiceal stump closure span a variety of techniques
      including ligation using intra-corporeal knots, extra-corporeal knots, or an endo
      loop (EL), closure with endoscopic clips (EC), or endoscopic stapled (ES)
      closure. The guiding principles are the need for secure, inert closure of the
      appendiceal base without injury to the appendiceal stump or cecum, with minimal
      risks of complication attributable to the closure technique. Safety and
      complication rates, as well as cost data, should guide the techniques used for
      pediatric laparoscopic appendectomy. Based on the literature available there is
      not a clear answer as to the best method for closing the appendiceal stump in
      pediatric patients, with each of the methods described providing safe closure.
      Many institutions and surgeons may favor a selective approach, with choice of
      closure determined by the condition of the appendix at laparoscopy. 

PMID- 23975449
TI  - The use of barbed suture in hysterectomy and myomectomy.
AB  - Standard sutures used in vaginal cuff reapproximation in total laparoscopic
      hysterectomies and hysterotomy closure in myomectomies require knot placement and
      tensioning of the suture throughout the closure. This may contribute to wound
      dehiscence, increased blood loss, and ischemia of tissue surrounding the knots.
      In 2004, the United States Food and Drug Administration approved the QuillTM
      bidirectional barbed suture (Angiotech Pharmaceuticals, Inc., Vancouver, BC,
      Canada)(Fig. 1). In January 2007, the suture was introduced in the United States.
      The emergence of the bidirectional barbed suture has significantly affected
      minimally invasive surgery. Initially used by orthopaedic and plastic surgeons,
      barbed suture has allowed for the tedious task of knot tying to fade away.
      Following the introduction of the bidirectional barbed suture, the FDA approved
      the V-LocTM unidirectional suture (Covidien, Mansfield, MA)(Fig. 2). The utility
      of the barbed suture has been instrumental in laparoscopic myomectomy and total
      laparoscopic hysterectomy. As barbed suture is easily utilized using the same
      laparoscopic ports, needle drivers, and graspers, the surgeon does not require a
      third hand to facilitate laparoscopic suturing. The barbs minimize tissue recoil
      and do so with accurate soft tissue approximation, achieving hemostasis without
      the use of locking and figure eight sutures. Barbed suture allows for a shorter
      operative time, as there is an ease of suturing without the complication of knot
      tying. Barbed sutures are essential tools in the modern laparoscopist's toolbox. 

PMID- 23975450
TI  - Effective oral psoralen plus ultraviolet a therapy for digital ulcers with
      revascularization in systemic sclerosis.

PMID- 23975453
TI  - White matter structural connectivity underlying semantic processing: evidence
      from brain damaged patients.
AB  - Widely distributed brain regions in temporal, parietal and frontal cortex have
      been found to be involved in semantic processing, but the anatomical connections
      supporting the semantic system are not well understood. In a group of 76 right
      handed brain-damaged patients, we tested the relationship between the integrity
      of major white matter tracts and the presence of semantic deficits. The integrity
      of white matter tracts was measured by percentage of lesion voxels obtained in
      structural imaging and mean fractional anisotropy values obtained in diffusion
      tensor imaging. Semantic deficits were assessed by jointly considering the
      performance on three semantic tasks that vary in the modalities of input (visual
      and auditory stimuli) and output (oral naming and associative judgement). We
      found that the lesion volume and fractional anisotropy value of the left inferior
      fronto-occipital fasciculus, left anterior thalamic radiation, and left uncinate
      fasciculus significantly correlated with severity of impairment in all three
      semantic tasks. These associations remained significant even when we controlled
      for a wide range of potential confounding variables, including overall cognitive
      state, whole lesion volume, or type of brain damage. The effects of these three
      white matter tracts could not be explained by potential involvement of relevant
      grey matter, and were (relatively) specific to object semantic processing, as no
      correlation with performance on non-object semantic control tasks (oral
      repetition and number processing tasks) was observed. These results underscore
      the causal role of left inferior fronto-occipital fasciculus, left anterior
      thalamic radiation, and left uncinate fasciculus in semantic processing,
      providing direct evidence for (part of) the anatomical skeleton of the semantic
      network. 

PMID- 23975451
TI  - Lifecourse health development: past, present and future.
AB  - During the latter half of the twentieth century, an explosion of research
      elucidated a growing number of causes of disease and contributors to health.
      Biopsychosocial models that accounted for the wide range of factors influencing
      health began to replace outmoded and overly simplified biomedical models of
      disease causation. More recently, models of lifecourse health development (LCHD)
      have synthesized research from biological, behavioral and social science
      disciplines, defined health development as a dynamic process that begins before
      conception and continues throughout the lifespan, and paved the way for the
      creation of novel strategies aimed at optimization of individual and population
      health trajectories. As rapid advances in epigenetics and biological systems
      research continue to inform and refine LCHD models, our healthcare delivery
      system has struggled to keep pace, and the gulf between knowledge and practice
      has widened. This paper attempts to chart the evolution of the LCHD framework,
      and illustrate its potential to transform how the MCH system addresses social,
      psychological, biological, and genetic influences on health, eliminates health
      disparities, reduces chronic illness, and contains healthcare costs. The LCHD
      approach can serve to highlight the foundational importance of MCH, moving it
      from the margins of national debate to the forefront of healthcare reform
      efforts. The paper concludes with suggestions for innovations that could
      accelerate the translation of health development principles into MCH practice.

PMID- 23975454
TI  - Inhibitors of the cyclooxygenase oxidation pathway of arachidonic acid suppress
      the stimulating effect of glutoxim on Na(+) transport in frog skin.

PMID- 23975455
TI  - Involvement of microtubules in the effects of glutoxim and molixan on the
      intracellular concentration of Ca(2+) in macrophages.

PMID- 23975452
TI  - Genotype-phenotype correlations in neurogenetics: Lesch-Nyhan disease as a model
      disorder.
AB  - Establishing meaningful relationships between genetic variations and clinical
      disease is a fundamental goal for all human genetic disorders. However, these
      genotype-phenotype correlations remain incompletely characterized and sometimes
      conflicting for many diseases. Lesch-Nyhan disease is an X-linked recessive
      disorder that is caused by a wide variety of mutations in the HPRT1 gene. The
      gene encodes hypoxanthine-guanine phosphoribosyl transferase, an enzyme involved
      in purine metabolism. The fine structure of enzyme has been established by
      crystallography studies, and its function can be measured with very precise
      biochemical assays. This rich knowledge of genetic alterations in the gene and
      their functional effect on its protein product provides a powerful model for
      exploring factors that influence genotype-phenotype correlations. The present
      study summarizes 615 known genetic mutations, their influence on the gene
      product, and their relationship to the clinical phenotype. In general, the
      results are compatible with the concept that the overall severity of the disease
      depends on how mutations ultimately influence enzyme activity. However, careful
      evaluation of exceptions to this concept point to several additional genetic and
      non-genetic factors that influence genotype-phenotype correlations. These factors
      are not unique to Lesch-Nyhan disease, and are relevant to most other genetic
      diseases. The disease therefore serves as a valuable model for understanding the
      challenges associated with establishing genotype-phenotype correlations for other
      disorders. 

PMID- 23975456
TI  - Mechanism of increasing the rate of agglutination of human erythrocytes under the
      influence of adrenaline and its relation to eryptosis.

PMID- 23975457
TI  - The effect of agmatine on the rhythmoinotropic properties of the cardiac
      papillary muscle of hibernating animals.

PMID- 23975458
TI  - Ischemia-reperfusion injury in intra-abdominal hypertension in experiment and
      clinic.

PMID- 23975459
TI  - The effect of leu- and met-enkephalins on lymphocyte proliferative response in
      men and women of different ages.

PMID- 23975460
TI  - Assortative mating in the hybrid zones of the common shrew (Sorex araneus
      mammalia) chromosome race West Dvina.

PMID- 23975461
TI  - Functional diversification of two MADS-Box genes, HAM45 and HAM59, in sunflower.

PMID- 23975462
TI  - The somatic musculature of the rotifer Trichotria pocillum (Rotifera:
      Transversiramida).

PMID- 23975463
TI  - Biogenic amines in the nervous system of nemerteans.

PMID- 23975464
TI  - Divergence of introns in the paralogous growth hormone genes of salmonid fish
      indicates the effect of selection.

PMID- 23975465
TI  - The structure of the nervous system and muscles of the pygidium in the polychaete
      Alitta virens (Nereididae).

PMID- 23975466
TI  - Viral community of biofilms forming on different substrates under natural
      conditions of Lake Baikal.

PMID- 23975467
TI  - Morphofunctional alterations in the stomach of the Sunda pangolin (Manis javanica
      Desmarest, 1822, Pholidota, Mammalia) associated with specific nutrition
      features.

PMID- 23975468
TI  - Serotonin and FMRFamide immunoreactive elements in the nervous system of
      freshwater bryozoans (Bryozoa: Phylactolaemata).

PMID- 23975469
TI  - Antitumor effect of the LIVP-GFP recombinant vaccinia virus.

PMID- 23975470
TI  - Green light regulates plastid gene transcription and stimulates the accumulation
      of photosynthetic pigments in plants.

PMID- 23975471
TI  - New data on molecular phylogeny of the East Asian moles.

PMID- 23975472
TI  - Jails: the new frontier. HIV testing, treatment, and linkage to care after
      release.

PMID- 23975473
TI  - Effectiveness of structural-level needle/syringe programs to reduce HCV and HIV
      infection among people who inject drugs: a systematic review.
AB  - Needle-syringe programs (NSP) have been effective in reducing HIV and hepatitis C
      (HCV) infection among people who inject drugs (PWID). Achieving sustainable
      reductions in these blood-borne infections requires addressing structural factors
      so PWID can legally access NSP services. Systematic literature searches collected
      information on NSP coverage and changes in HIV or HCV infection prevalence or
      incidence at the population level. Included studies had to document biomarkers
      (HIV or HCV) coupled with structural-level NSP, defined by a minimum 50 %
      coverage of PWID and distribution of 10 or more needles/syringe per PWID per
      year. Fifteen studies reported structural-level NSP and changes in HIV or HCV
      infection prevalence/incidence. Nine reported decreases in HIV prevalence, six in
      HCV infection prevalence, and three reported decreases in HIV incidence. The
      results support NSP as a structural-level intervention to reduce population-level
      infection and implementation of NSP for prevention and treatment of HIV and HCV
      infection. 

PMID- 23975474
TI  - Randomized controlled trial to evaluate the impact of pharmaceutical care on
      therapeutic success in HIV-infected patients in Southern Brazil.
AB  - A non-blinded randomized controlled trial evaluated efficacy of pharmaceutical
      care (PC) (Dader method) on self-reported antiretroviral adherence and
      undetectable plasma viral load (UPVL), compared with usual care (UC) in HIV
      positive patients in Brazil. Most were male (63 %), mean age 40.3 years (SD =
      10). After 12 months, 79.8 % of those receiving PC versus 73.8 % in UC were
      adherent (RR 1.05, 95 % CI 0.95-1.15, P = 0.35), and 50.3 versus 49.8 % (PC vs.
      UC, respectively) had UPVL (RR 1.08, 95 % CI 0.97-1.20, P = 0.15). Factors
      associated with self-reported adherence were regular employment, UPVL, no
      depressive symptoms, and lower pill load in the treatment regimen. Older age,
      education, CD4 count <200 cells/mm(3), and shorter treatment duration were
      associated with UPVL. Of 94 reported drug-related problems, 43 % resolved. In
      subgroup analyses of patients who experienced therapeutic failure and who were
      non-adherent at the beginning of the trial (N = 50), no differences were found in
      UPVL (HR 1.35, 95 % CI 0.57-3.19). Only education level (>12 years) was
      independently predictive of viral suppression (HR 7.47, 95 % CI 1.69-32.91). In
      conclusion, PC was not associated with increased self-reported adherence to ART
      or UPVL in patients treated at a health care facility in southern Brazil. The
      study suggests, however, that PC could be effective for the subgroup of patients
      with poor adherence. 

PMID- 23975475
TI  - Affect management for HIV prevention with adolescents in therapeutic schools: the
      immediate impact of project balance.
AB  - Adolescents in therapeutic schools are at greater risk for HIV and other STIs
      than their peers due to earlier higher rates of sexual risk and difficulty
      managing strong emotions. HIV prevention programs that incorporate techniques for
      affect management (AM) during sexual situations may be beneficial. This paper
      determined the immediate impact of such an intervention, AM, compared to a
      standard, skills-based HIV prevention intervention and a general health promotion
      intervention (HP) for 377 youth, ages 13-19, in therapeutic schools in two
      cities. 1 month after the intervention, analyses that adjusted for the baseline
      scores found adolescents in AM were more likely to report condom use at last sex
      than those in HP (0.89 vs. 0.67, p = 0.02) and that their HIV knowledge was
      significantly greater. These data suggest that AM techniques might improve the
      impact of standard skills-based prevention programs for adolescents in
      therapeutic schools.

PMID- 23975476
TI  - Does effective depression treatment alone reduce secondary HIV transmission risk?
      Equivocal findings from a randomized controlled trial.
AB  - Depressed mood has been associated with HIV transmission risk behavior. To
      determine whether effective depression treatment could reduce the frequency of
      sexual risk behavior, we analyzed secondary outcome data from a 36-week, two-arm,
      parallel-design, randomized controlled trial, in which homeless and marginally
      housed, HIV-infected persons with comorbid depressive disorders were randomized
      to receive either: (a) directly observed treatment with the antidepressant
      medication fluoxetine, or (b) referral to a local public mental health clinic.
      Self-reported sexual risk outcomes, which were measured at 3, 6, and 9 months,
      included: total number of sexual partners, unprotected sexual intercourse,
      unprotected sexual intercourse with an HIV-uninfected partner or a partner of
      unknown serostatus, and transactional sex. Estimates from generalized estimating
      equations regression models did not suggest consistent reductions in sexual risk
      behaviors resulting from treatment. Mental health interventions may need to
      combine depression treatment with specific skills training in order to achieve
      durable impacts on HIV prevention outcomes.

PMID- 23975477
TI  - Transitions in latent classes of sexual risk behavior among young injection drug
      users following HIV prevention intervention.
AB  - We analyzed data from a large randomized HIV/HCV prevention intervention trial
      with young injection drug users (IDUs). Using categorical latent variable
      analysis, we identified distinct classes of sexual behavior for men and women. We
      conducted a latent transition analysis to test the effect of the intervention on
      transitions from higher to lower risk classes. Men who were in a high-risk class
      at baseline who received the intervention were 86 % more likely to be in a low
      risk class at follow-up compared to those in the control group (p = 0.025). High
      risk intervention participants were significantly more likely to transition to
      the class characterized by unprotected sex with a main partner only, while low
      risk intervention participants were significantly less likely to transition to
      that class. No intervention effect was detected on the sexual risk behavior of
      women, or of men who at baseline were having unprotected sex with a main partner
      only.

PMID- 23975478
TI  - Association between vestibular schwannomas and mobile phone use.
AB  - Vestibular schwannomas (VSs) grow in the region where the energy from mobile
      phone use is absorbed. We examined the associations of VSs with mobile phone use.
      This study included 119 patients who had undergone surgical tumor removal. We
      used two approaches in this investigation. First, a case-control study for the
      association of mobile phone use and incidence of VSs was conducted. Both cases
      and controls were investigated with questions based on INTERPHONE guidelines.
      Amount of mobile phone use according to duration, daily amount, and cumulative
      hours were compared between two groups. We also conducted a case-case study. The
      location and volume of the tumors were investigated by MRI. Associations between
      the estimated amount of mobile phone use and tumor volume and between the
      laterality of phone use and tumor location were analyzed. In a case-control
      study, the odds ratio (OR) of tumor incidence according to mobile phone use was
      0.956. In the case-case study, tumor volume and estimated cumulative hours showed
      a strong correlation (r(2) = 0.144, p = 0.002), and regular mobile phone users
      showed tumors of a markedly larger volume than those of non-regular users (p <
      0.001). When the analysis was limited to regular users who had serviceable
      hearing, laterality showed a strong correlation with tumor side (OR = 4.5). We
      found that tumors may coincide with the more frequently used ear of mobile phones
      and tumor volume that showed strong correlation with amount of mobile phone use,
      thus there is a possibility that mobile phone use may affect tumor growth.

PMID- 23975479
TI  - Extended mind and after: socially extended mind and actor-network.
AB  - The concept of extended mind has been impressively developed over the last 10
      years by many philosophers and cognitive scientists. The extended mind thesis
      (EM) affirms that the mind is not simply ensconced inside the head, but extends
      to the whole system of brain-body-environment. Recently, some philosophers and
      psychologists try to adapt the idea of EM to the domain of social cognition
      research. Mind is socially extended (SEM). However, EM/SEM theory has problems to
      analyze the interactions among a subject and its surroundings with opposition,
      antagonism, or conflict; it also tends to think that the environment surrounding
      the subject is passive or static, and to neglect the power of non-human actants
      to direct and regulate the human subject. In these points, actor-network theory
      (ANT) proposed by Latour and Callon is more persuasive, while sharing some
      important ideas with EM/SEM theory. Actor-network is a hybrid community which is
      composed of a series of heterogeneous elements, animate and inanimate for a
      certain period of time. I shall conclude that EM/SEM could be best analyzed as a
      special case of actor-network. EM/SEM is a system which can be controlled by a
      human agent alone. In order to understand collective behavior, philosophy and
      psychology have to study the actor-network in which human individuals are
      situated. 

PMID- 23975480
TI  - Utility of multimodal cardiac imaging with PET/MRI in cardiac sarcoidosis:
      implications for diagnosis, monitoring and treatment.

PMID- 23975481
TI  - Case reports in medicine.

PMID- 23975482
TI  - Endoscopic view of the drainage pathway of a pneumatized uncinate process.

PMID- 23975483
TI  - Iatrogenic epiglottic inversion during intubation.

PMID- 23975485
TI  - Nasopharyngeal yolk sac tumors: a rare pediatric occurrence.

PMID- 23975484
TI  - Transnasal esophagoscopy and the diagnosis of a mediastinal foregut duplication
      cyst.

PMID- 23975486
TI  - Middle ear effusion in adult ICU patients: a cohort study.
AB  - We conducted a prospective study of 74 adults-34 men and 40 women, aged 18 to 90
      (mean: 60.2)-to determine the prevalence of middle ear effusion (MEE) among
      patients in the setting of an intensive care unit (ICU) and to compare the
      findings with those of a control group of non-ICU hospitalized patients. Other
      goals were to identify risk factors associated with MEE in ICU patients and to
      evaluate any association with fever. Both groups included 37 patients. MEE was
      present in 19 patients (51.4%) in the ICU group, compared with only 2 patients
      (5.4%) in the control group (p < 0.01; odds ratio: 18.5; 95% confidence interval:
      3.9 to 88.3). In the ICU group, there were statistically significant associations
      between MEE and both the use of mechanical ventilation (p = 0.03) and the use of
      sedation (p = 0.02). No significant relationships were seen in terms of length of
      stay, body position, the use of an endotracheal tube, the length of ventilation,
      and the use of a feeding tube. Fever was present in 8 ICU patients (21.6%) and 3
      controls (8.1%), but none of the fevers was associated with MEE. We conclude that
      adult ICU patients have a high prevalence of MEE (51.4% in our sample) that is
      perhaps unrecognized. We believe that MEE in these patients is most likely
      related to altered consciousness, sedation, and mechanical ventilation. MEE was
      an unlikely cause of fever. 

PMID- 23975487
TI  - Thiersch skin grafting in otologic surgery.
AB  - Thiersch skin grafting is an old but highly effective surgical technique in
      otology. We frequently place a Thiersch graft after otologic procedures that
      either create a mastoid cavity or result in reduced skin coverage of a portion of
      the external auditory canal. The purpose of this article is to introduce this
      surgical technique to a new generation of otologists. We discuss its indications,
      the surgical technique, tips for a successful outcome, and postoperative care. A
      key to successful skin grafting is to perform the procedure about 10 days after
      the primary procedure to allow sufficient time for the formation of an adequate
      vascular bed at the recipient site. The goal in all cases is to achieve a safe,
      dry ear that is covered with keratinizing squamous epithelium. Thiersch grafting
      accomplishes this very well. 

PMID- 23975490
TI  - A systematic review of proton-pump inhibitor therapy for laryngopharyngeal
      reflux.
AB  - The author performed a MEDLINE literature search to identify and evaluate all
      randomized, placebo-controlled trials of the treatment of laryngopharyngeal
      reflux (LPR) with an oral proton-pump inhibitor (PPI) that have been published
      since 1966. Eight such trials that included a total of 358 patients were
      identified. These eight studies contained seven different definitions of LPR.
      Validity scores (maximum: 9) ranged from 5 to 9 (mean: 7.5). One study
      investigated low-dose once-daily therapy, two studies investigated low-dose twice
      daily therapy, and five studies investigated high-dose twice-daily therapy.
      Outcomes measures were not consistent among studies, and most studies used
      unvalidated outcomes measures. Only two studies found that a PPI was
      significantly better than placebo-one in the low-dose twice-daily group and one
      in the high-dose twice-daily group. The author concludes that the current body of
      literature is insufficient to draw reliable conclusions about the efficacy of PPI
      therapy for the treatment of LPR. 

PMID- 23975493
TI  - Comparison of complication rates associated with stapling and traditional suture
      closure after total laryngectomy for advanced cancer.
AB  - We conducted a retrospective, matched-cohort, case-control study to compare
      complication rates associated with two wound closure procedures-stapling vs.
      traditional hand suturing-following total laryngectomy. Our study population was
      made up of 42 consecutively presenting patients-38 men and 4 women, aged 34 to 92
      years (mean: 60.3) whose pharyngotomies were amenable to primary closure. Of this
      group, 37 patients had active endolaryngeal squamous cell carcinoma (SCC), 2
      patients had inactive endolaryngeal SCC, 2 patients had thyroid cancer, and 1
      patient had been treated for chronic aspiration. A total of 26 patients (61.9%)
      had undergone traditional suture closure of the neopharynx (suture group) and 16
      patients (38.1%) had undergone closure with a linear stapling device (staple
      group). Other than the fact that the patients in the staple group were
      significantly older than those in the suture group (median: 71.0 vs. 56.5 yr, p =
      0.002), there were no significant differences between the two groups in terms of
      comorbidities or cricopharyngeal myotomy, tracheoesophageal puncture, or neck
      dissection. There was a total of 8 postoperative infections-5 in the staple group
      (31.3%) and 3 in the suture group (11.5%)-not a statistically significant
      difference. Fistulas occurred in 4 staple patients (25.0%) and 6 suture patients
      (23.1%)-again, not statistically significant. We conclude that in appropriately
      selected patients, primary closure of the neopharynx can be safely and
      effectively achieved with a linear stapling device. 

PMID- 23975488
TI  - Transient auditory dysfunction: a description and study of prevalence.
AB  - Transient auditory dysfunction (TAD) is a previously undescribed symptom complex
      of unknown cause. It is characterized by short-lasting sensorineural hearing loss
      (unilateral or bilateral), it is associated with tinnitus, it resolves completely
      within minutes, and it is not accompanied by vestibular symptoms. We conducted a
      cross-sectional prospective study to define TAD, find its prevalence, and discuss
      its significance. Two hundred healthy subjects between the ages of 16 and 49
      years were surveyed using a questionnaire. Of these subjects, 41 (20.5%) reported
      experiencing symptoms of TAD. The mean number of episodes was 5.9 times per
      month, the mean duration was 41 seconds, and 80% experienced concomitant
      tinnitus. We conclude that TAD is a common finding in a healthy population. This
      may have implications for the pathogenesis of sudden-onset sensorineural hearing
      loss. Further longitudinal studies and detailed audiologic evaluation of patients
      with TAD are required to ascertain the significance, etiology, and
      pathophysiology of this condition. 

PMID- 23975489
TI  - The impact of pulmonary tuberculosis treatment on the prevalence of allergic
      rhinitis.
AB  - Atopy is a syndrome characterized by immediate hypersensitivity reactions to
      common environmental antigens. The "hygiene hypothesis" stipulates that childhood
      infections are associated with a lower risk of allergies. Not much has been
      published about the effects that the treatment of pulmonary tuberculosis (TB) has
      on allergies, specifically allergic rhinitis. We conducted a study to investigate
      the prevalence of allergic rhinitis in patients with pulmonary TB before and
      after treatment of their TB. Our initial study group was made up of 121 patients
      with confirmed pulmonary TB who were followed up by questionnaire. In addition to
      demographic data, they provided information about their personal and family
      history of atopy and their current status with regard to allergic rhinitis. After
      providing informed consent, all patients underwent skin-prick testing with
      Dermatophagoides pteronyssinus, Dermatophagoides farinae, and Blomia tropicalis
      allergens before and after TB treatment. Stool samples were obtained to identify
      patients with worm infestation, and they were excluded from the study. In all, 94
      patients completed treatment and follow-up, and their data were included in the
      final analysis. Of this group, 31 patients (33.0%) exhibited symptoms of allergic
      rhinitis prior to TB treatment, and 26 (27.7%) had a positive skin-prick test.
      Following treatment, only 12 patients (12.8%) reported allergic rhinitis symptoms
      (p = 0.004), but there was no significant reduction in the number of patients
      with a positive skin-prick test (n = 20 [21.3%]; p = 0.555). We conclude that the
      treatment of pulmonary TB results in significant relief of atopy, particularly
      allergic rhinitis symptoms. 

PMID- 23975492
TI  - Post-thyroidectomy early serum ionic calcium level: predictor of prolonged
      hypocalcemia.
AB  - One of the more common complications of thyroid surgery is postoperative
      hypocalcemia, which is potentially serious. Its clinical manifestations range
      from minimal twitching to life-threatening tetany. Affected patients might
      require a prolonged hospital stay and supplementation with calcium and vitamin D.
      In cases of post-thyroidectomy hypocalcemia, it is not always easy to predict
      which patients will require close monitoring of serum calcium levels. We
      conducted a study to determine whether early (<24 hr) measurement of serum ionic
      calcium (SiCa) levels can predict the development of post-thyroidectomy
      hypocalcemia. We retrospectively analyzed the charts of 150 adults (144 women and
      6 men) who had undergone total or partial thyroidectomy, and we identified 42
      patients (all women) who had either transient (<1 mo; n = 27) or prolonged (1 to
      6 mo; n = 15) temporary hypocalcemia. We found that the patients who turned out
      to have prolonged hypocalcemia had significantly lower early levels of SiCa than
      did the patients who later developed only transient hypocalcemia (p = 0.000002).
      Also, patients with prolonged hypocalcemia had a significantly higher incidence
      of serious sequelae, including carpopedal spasms and signs of tetany. We conclude
      that early measurement of SiCa is a reliable predictor of prolonged temporary
      hypocalcemia following total or partial thyroidectomy. 

PMID- 23975496
TI  - Migration of a fish bone from the upper aerodigestive tract to the skin of the
      neck: a case report.
AB  - We describe an unusual case of a migratory foreign body (fish bone) in the neck
      of a 45-year-old woman. The 2.1-cm bone migrated from the esophagus and traversed
      through the entire soft tissue of the neck, and it almost extruded through the
      skin of the neck. With the patient under local anesthesia, the foreign body was
      easily extracted through an incision over the skin. 

PMID- 23975494
TI  - Multilevel treatment of moderate and severe obstructive sleep apnea with bone
      anchored pharyngeal suspension sutures.
AB  - Success rates for the surgical treatment of obstructive sleep apnea (OSA) vary,
      with phase I surgical success ranging from 40 to 75%. Pharyngeal suspension
      suture procedures are minimally invasive techniques with a reported efficacy of
      20 to 78%. We conducted a study to evaluate the effectiveness of pharyngeal
      suspension suture procedures in conjunction with uvulopalatopharyngoplasty (UPPP)
      as a multilevel treatment for OSA. We retrospectively reviewed the charts of 30
      adults-22 men and 8 women, with a mean age of 49 years and a mean BMI of 30.6-who
      were treated at a tertiary care academic medical center and a private
      otolaryngology practice. All patients had moderate or severe OSA, and all had
      failed continuous positive airway pressure therapy. Of this group, 20 patients
      underwent tongue base and hyoid suspension (TBHS) and 10 underwent tongue base
      suspension (TBS) alone; 23 patients had undergone concurrent or previous UPPP, 13
      in the TBHS group and all 10 in the TBS group. Polysomnography was performed an
      average of 3.9 months postoperatively. Surgical success was defined as a
      reduction in respiratory distress index (RDI) of more than 50% and a
      postoperative RDI of 20 or less. The overall surgical success rate was 63%
      (19/30). In the surgical success group, the mean RDI fell from 44.6 to 9.4 (p <
      0.0001); in the surgical failure group, the mean RDI rose from 41.3 to 48.9 (p =
      0.58). There were 6 complications: 3 seromas, 2 suture breaks, and 1 dislodged
      screw. We conclude that pharyngeal suspension suture procedures as part of the
      multilevel treatment of moderate and severe OSA yields better outcomes than
      conventional surgical treatments with the added benefit of being minimally
      invasive. 

PMID- 23975495
TI  - Traumatic tracheostomy and spent bullet aspiration after a gunshot injury: a case
      report.
AB  - Penetrating tracheal injuries are rare. Even rarer is the finding of
      intrabronchial foreign bodies caused by penetrating objects. We report a patient
      who experienced a gunshot injury to the trachea and mandible. The tracheal wound
      was debrided and used as a tracheostomy; a spent bullet in the bronchial tree was
      missed on initial evaluation but later successfully retrieved bronchoscopically.
      Spent bullet aspiration is a very rare occurrence. A careful examination of
      radiographs is essential to aid with the diagnosis. Flexible bronchoscopy is the
      best means of bullet retrieval. Management of any associated injuries is made
      easier after the airway is secured. 

PMID- 23975491
TI  - Human papillomavirus and tobacco use in tongue base cancers.
AB  - Human papillomavirus 16 (HPV-16) infection and tobacco use are associated with
      human oropharyngeal cancers. We conducted a study of the role of HPV and tobacco
      use in base of the tongue (BOT) cancers. DNA from 34 such cancers was subjected
      to HPV-16 and HPV-18-specific polymerase chain reaction analysis. Demographic and
      clinicopathologic data were obtained from each patient's medical record. HPV-16
      was detected in 68% of tumors. Tobacco use was the only factor found to be
      significantly associated with HPV status. Tumors from 100% of patients who had
      never used tobacco tested positive for HPV, compared with only 56% of those who
      had ever used tobacco (Fisher exact test, p = 0.024). All tumors were associated
      with either tobacco use or HPV infection. These findings are consistent with the
      hypothesis that either tobacco use or HPV infection is necessary to the etiology
      of BOT tumors, and they suggest that tongue base carcinoma may be prevented by
      combining HPV vaccination with tobacco avoidance. 

PMID- 23975497
TI  - Late-onset complications after chemoradiation for head and neck carcinomas.
AB  - Acute complications from chemoradiation for head and neck cancers are relatively
      common. These can be minor or severe and can have a significant impact on the
      patient's quality of life. The incidence of late-onset (>5 years after cancer
      cure) complications is unknown, but the effect on quality of life is just as
      severe as with acute problems. What makes matters worse is that many of these
      patients lived years without dysphagia or other issues and were able to resume a
      normal lifestyle before developing complications. We present 4 cases involving
      patients with late-onset complications and discuss the need to remain vigilant in
      follow-up and caring for patients with head and neck cancer. 

PMID- 23975498
TI  - Analysis of the vertebrobasilar system in patients with obstructive sleep apnea.
AB  - We conducted a prospective study to evaluate the vertebrobasilar system in adults
      with and without obstructive sleep apnea (OSA). Our study population was made up
      of 48 patients with OSA and 21 healthy volunteers who served as controls; the OSA
      patients were subdivided into one group with mild or moderate OSA (n = 22) and
      another with severe OSA (n = 26). Each participant underwent Doppler
      ultrasonography three times to measure the diameter of the vertebral artery, the
      peak systolic velocity (PSV), the resistive index (RI), and the vertebral artery
      flow volume; the mean of the three measurements was calculated for each patient,
      for the OSA and control groups, and for various subgroups. No significant
      differences in vessel diameter, PSV, or RI were seen among any of the subgroups.
      Overall, the vertebral artery flow volume was slightly, but not significantly,
      higher in all patients with OSA (206 ml/min) than in the control group (177
      ml/min); this difference might reflect the body's daytime response to the chronic
      apneic events experienced during sleep. The only statistically significant
      difference we found was in vertebral artery flow volume between the controls and
      the subgroup with mild or moderate OSA (p = 0.026); no difference was seen
      between the controls and the patients with severe OSA (p = 0.318). Likewise, no
      significant difference in any of the four parameters was seen when patients were
      subclassified by body mass index and arterial oxygen saturation level. 

PMID- 23975499
TI  - Peripheral osteoma of the hard palate.
AB  - Peripheral osteomas of the hard palate are relatively rare. Two cases of osteoma
      of the hard palate are reported, along with a review of the literature. 

PMID- 23975500
TI  - Ganglion cyst in the external auditory canal.

PMID- 23975501
TI  - Extensive dentigerous cyst associated with a mesiodens: CT findings.
AB  - The most common of the supernumerary teeth in humans are mesiodentes, which arise
      in the midline of the maxilla between the central incisors. The most common
      pathologic findings associated with a mesiodens are retention of the adjacent
      incisors, malposition, and diastema. The development of a dentigerous cyst in
      association with an impacted mesiodens is relatively uncommon. We report the case
      of a 35-year-old man with an extensive dentigerous cyst associated with a
      mesiodens who presented with a painful swelling in the left nasolabial area. We
      discuss the imaging findings in this case, particularly the contribution of
      computed tomography, and we review the literature on this interesting condition. 

PMID- 23975502
TI  - Mummified leiomyoma of the midline anterior neck: Case report and literature
      review.
AB  - Leiomyomas are benign smooth-muscle tumors that have only rarely been reported in
      the head and neck. Extensive calcification (mummification) is occasionally seen
      in deep somatic soft-tissue leiomyomas, which represent a rare subtype. We
      describe a case of mummified leiomyoma of the soft tissues of the midline
      anterior neck in a 31-year-old man. His tumor was successfully managed with
      surgical excision. To the best of our knowledge, this case represents the only
      description of a mummified leiomyoma at this particular site and the first
      reported case of any leiomyoma at this site in more than 50 years. We also review
      the literature concerning leiomyomas of the head and neck, their subtypes,
      diagnostic and management considerations, and outcomes. 

PMID- 23975503
TI  - The Understanding of Terminal Cancer and Its Relationship with Attitudes toward
      End-of-Life Care Issues.
AB  - BACKGROUND: Although terminal cancer is a widely used term, its meaning varies,
      which may lead to different attitudes toward end-of-life issues. The study was
      conducted to investigate differences in the understanding of terminal cancer and
      determine the relationship between this understanding and attitudes toward end-of
      life issues. METHODS: A questionnaire survey was performed between 2008 and 2009.
      A total of 1242 cancer patients, 1289 family caregivers, 303 oncologists from 17
      hospitals, and 1006 participants from the general population responded. RESULTS:
      A "6-month life expectancy" was the most common understanding of terminal cancer
      (45.6%), followed by "treatment refractoriness" (21.1%), "metastatic/recurrent
      disease" (19.4%), "survival of a few days/weeks" (11.4%), and "locally advanced
      disease" (2.5%). The combined proportion of "treatment refractoriness" and "6
      month life expectancy" differed significantly between oncologists and the other
      groups combined (76.0% v. 65.9%, P = 0.0003). Multivariate analyses showed that
      patients and caregivers who understood terminal cancer as "survival of a few
      days/weeks" showed more negative attitudes toward disclosure of terminal status
      compared with participants who chose "treatment refractoriness" (adjusted odds
      ratio [aOR] 0.42, 95% confidence interval [CI] 0.22-0.79 for patients; aOR 0.34,
      95% CI 0.18-0.63 for caregivers). Caregivers who understood terminal cancer as
      "locally advanced" or "metastatic/recurrent disease" showed a significantly lower
      percentage of agreement with withdrawal of futile life-sustaining treatment
      compared with those who chose "treatment refractoriness" (aOR 0.19, 95% CI 0.07
      0.54 for locally advanced; aOR 0.39, 95% CI 0.21-0.72 for metastatic/recurrent).
      CONCLUSIONS: The understanding of terminal cancer varied among the 4 participant
      groups. It was associated with different preferences regarding end-of-life
      issues. Standardization of these terms is needed to better understand end-of-life
      care.

PMID- 23975504
TI  - Platelet-activating factor induces proliferation in differentiated keratinocytes.
AB  - Increased levels of platelet-activating factor (PAF; 1-O-alkyl-2-acetyl-sn
      glycero-3-phosphocholine) are found in several inflammatory dermatoses, but PAF's
      exact role in epidermis is uncertain. In order to better understand the
      physiological consequences of excess PAF production in epidermis, we examined the
      gene regulatory effects of PAF short-term stimulation in differentiated HaCaT
      keratinocytes by transcriptional profiling. Even though PAF induces COX2
      expression, we found that PAF regulates only few genes associated with
      inflammation in differentiated keratinocytes. Rather, we show that natural PAF
      rapidly regulates genes involved in proliferation, (anti)-apoptosis and
      migration, all sub-processes of re-epithelialization and wound healing. Moreover,
      profiling of phosphorylated kinases, cellular wound-scratch experiments,
      resazurin assay and flow cytometry cell cycle phase analysis all support a role
      for PAF in keratinocyte proliferation and epidermal re-epithelialization. In
      conclusion, these results suggest that PAF acts as an activator of proliferation
      and may, therefore, function as a connector between inflammation and
      proliferation in differentiated keratinocytes. 

PMID- 23975505
TI  - Bisoprolol reversed small conductance calcium-activated potassium channel (SK)
      remodeling in a volume-overload rat model.
AB  - A recent study indicated that apamin-sensitive current (I KAS, mediated by apamin
      sensitive small conductance calcium-activated potassium channels subunits)
      density significantly increased in heart failure and led to recurrent spontaneous
      ventricular fibrillation. While the underlying molecular correlation with SK
      channels is still undetermined, we hypothesized that they are remodeled in HF and
      that bisoprolol could reverse the remodeling. Volume-overload models were created
      on male Sprague-Dawley rats by producing an abdominal arteriovenous fistula.
      Confocal microscopy, quantitative real-time PCR, and western blot were performed
      to investigate the expression of SK channels and observe the influence of beta
      blocker bisoprolol on the expression of SK channels I KAS, and the effect of
      bisoprolol on I KAS and the sensitivity of I KAS to [Ca(2+)]i at single isolated
      cells were also explored using whole-cell patch clamp techniques. SK channels
      were remodeled in HF rats, displaying the significant increase of SK1 and SK3
      channel expression. After the treatment of HF rats with bisoprolol, the
      expression of SK1 and SK3 channels was significantly downregulated, and
      bisoprolol effectively downregulated I KAS density as well as the sensitivity of
      I KAS to [Ca(2+)]i. Our data indicated that the expression of SK1 and SK3
      increased in HF. Bisoprolol effectively attenuated the change and downregulated I
      KAS density as well as the sensitivity of I KAS to [Ca(2+)]i. 

PMID- 23975506
TI  - miR-335 suppresses migration and invasion by targeting ROCK1 in osteosarcoma
      cells.
AB  - Accumulating evidence has shown that microRNAs are involved in multiple processes
      in cancer development and progression. Recently, miR-335 has been identified as a
      tumor-suppressing microRNA in many human cancers. However, the specific function
      of miR-335 in osteosarcoma is unclear at this point. In this study, we found that
      the expression of miR-335 in osteosarcoma tissues and cell lines was much lower
      than that in normal control, respectively, and the downregulated miR-335 was
      significantly associated with lymph-node metastasis. Transfection of miR-335
      mimics could significantly inhibit the cell migration and invasion in MG-63 and
      U2OS osteosarcoma cell lines. Moreover, we also showed that ROCK1 was negatively
      regulated by miR-335 at the posttranscriptional level, via a specific target site
      within the 3'UTR by luciferase reporter assay. The expression of ROCK1 was
      inversely correlated with miR-335 expression in osteosarcoma tissues, and
      knockdown of ROCK1 by siRNA-inhibited osteosarcoma cells migration and invasion
      resembling that of miR-335 overexpression. Thus, our findings suggest that miR
      335 acts as tumor suppressor by targeting the ROCK1 gene and inhibiting
      osteosarcoma cells migration and invasion. The findings of this study contribute
      to current understanding of the functions of miR-335 in osteosarcoma. 

PMID- 23975508
TI  - Acne: risk indicator for increased body mass index and insulin resistance.
AB  - Acne appears to represent a visible indicator disease of over-activated mTORC1
      signalling, an unfavour-able metabolic deviation on the road to serious common
      Western diseases of civilisation associated with increased body mass index and
      insulin resistance. Exaggerated mTORC1 signalling by Western diet explains the
      association of acne with increased body mass index, insulin resistance, and early
      onset of menarche. Both, a high glycaemic load and increased consumption of milk
      and milk products, staples of Western diet, aggravate mammalian target of
      rapamycin complex 1 signalling. This review of the literature summarises present
      evidence for an association between acne, increased body mass index, insulin
      resistance and Western diet. By dietary intervention with a Palaeolithic-type
      diet, the dermatologist has the chance to attenuate patients' increased mTORC1
      signalling by reducing glycaemic load and milk consumption, which may not only
      improve acne but may delay the march to more serious mTORC1-driven diseases of
      civilisation. 

PMID- 23975507
TI  - Diosgenin improves vascular function by increasing aortic eNOS expression,
      normalize dyslipidemia and ACE activity in chronic renal failure rats.
AB  - In recent years, the role of endothelial dysfunction (ED) and excessive oxidative
      stress in the development of cardiovascular diseases has been highlighted. The
      aim of the present study is to evaluate the effect of diosgenin, an antioxidant
      on chronic renal failure (CRF) induced vascular dysfunction. CRF was induced by
      feeding the rats with a diet containing 0.75 % adenine and diosgenin was given
      orally (everyday at the dose of 40 mg/kg). Isometric force measurement was
      performed on isolated aortic rings in organ baths. Levels of reduced glutathione
      (GSH), nitric oxide metabolites, and endothelial nitric oxide synthase mRNA in
      rat aorta were examined. Further, plasma lipid profile, activity of enzymes of
      lipid metabolism, and aortic angiotensin converting enzyme (ACE) also studied.
      The overall results have proved that diosgenin attenuates CRF-induced impairment
      in acetylcholine induced endothelium-dependent and sodium nitroprusside induced
      endothelium-independent vascular relaxation. Moreover, it elevates the GSH and
      restores the eNOS mRNA expression level. CRF-induced dyslipidemia and ACE
      activity was also inhibited by diosgenin treatment. This study indicates that
      diosgenin have enough potential to protect vasculature against oxidative stress,
      dyslipidemia which in turn improves the vascular function in CRF milieu. 

PMID- 23975509
TI  - A phase II study of cisplatin /S-1 in patients with carcinomas of unknown primary
      site.
AB  - BACKGROUND: Carcinomas of unknown primary site (CUPs) are heterogeneous tumors
      associated with a poor prognosis. This phase II trial was designed to evaluate
      the efficacy and safety of a novel combination chemotherapy of S-1 and cisplatin
      (CDDP) in patients with CUP. PATIENTS AND METHODS: Patients with previously
      untreated CUPs were eligible for this trial. The treatment schedule consisted of
      oral S-1 (40 mg/m(2)) twice a day on days 1-21, and intravenous CDDP (60 mg/m(2))
      on day 8. This schedule was repeated every 5 weeks. RESULTS: A total of 46
      patients were enrolled. The overall response rate and the disease control rate
      were 41.3% and 80.4%, respectively. The median overall survival time was 17.4
      months. Grade 3/4 neutropenia, thrombocytopenia, and febrile neutropenia occurred
      in 28.3%, 13.0%, and 2.2% of the patients, respectively. CONCLUSION: CDDP plus S
      1 combination chemotherapy is well tolerated and active first-line empiric
      therapies for patients with CUP.

PMID- 23975510
TI  - A phase I study of everolimus and CHOP in newly diagnosed peripheral T-cell
      lymphomas.
AB  - BACKGROUND: We performed a phase I study to determine the dose and safety of
      everolimus as a combination chemotherapy in peripheral T-cell lymphoma (PTCL).
      METHODS: Four dose levels (2.5 to 10 mg) of everolimus from days 1 to 14 with
      CHOP (750 mg/m(2) cyclophosphamide, 50 mg/m(2) doxorubicin, and 1.4 mg/m(2)
      (maximum 2 mg) vincristine on day 1, and 100 mg/day prednisone on days 1 to 5)
      every 21 days were planned. RESULTS: Fifteen patients newly diagnosed with stage
      III/IV PTCL were enrolled. One of 6 patients at dose level 2 (5 mg everolimus)
      had grade 3 hepatotoxicity and 3 of 6 patients at level 3 (7.5 mg everolimus) had
      grade 4 hematologic toxicities (two grade 4 thrombocytopenia and one grade 4
      neutropenia with fever lasting more than 3 days). The recommended dose of
      everolimus for combination was 5 mg. There were no differences in steady state
      trough concentrations of everolimus between cycles 1 and 2 for all three dose
      levels. All evaluable patients achieved response (8 complete and 6 partial).
      CONCLUSIONS: Everolimus (5 mg) can be safely combined with CHOP leading to a
      feasible and effective regimen for PTCL. The subsequent phase II is now in
      progress.

PMID- 23975512
TI  - Kazachstania psychrophila sp. nov., a novel psychrophilic yeast isolated from
      vacuum-packed beef.
AB  - Five novel ascosporogenous yeast strains (H382, H396, H409, H433(T) and H441)
      were found through a survey of vacuum-packed beef microbiota. Sequence analysis
      of ITS domain and LSU rRNA genes showed that the new strains represent a distinct
      lineage within the genus Kazachstania, closely related to Kazachstania lodderae
      (97.0 % identity) and Kazachstania ichnusensis (96.1 % identity). The main
      difference of strains H382, H396, H409, H433(T) and H441 to strains of known
      Kazachstania species is the maximum growth temperature, which is below 20 
      degrees C for the new strains, whereas related species grow at 25  degrees C.
      Furthermore, the strains differed from known Kazachstania species in assimilation
      and fermentation patterns of carbon sources. Based on these characteristics, the
      five strains are considered to represent a novel species of the genus
      Kazachstania for which the name Kazachstania psychrophila sp. nov. is proposed.
      The type strain is H433(T) (DSM 26230(T)=CBS 12689(T)). The Mycobank number of
      the type strain is MB 803980.

PMID- 23975511
TI  - Preclinical evaluation of the PI3K-mTOR dual inhibitor PF-04691502 as a novel
      therapeutic drug in nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is common in Southeast Asia and over 40% of NPC
      tissues have PIK3CA amplification. This study characterized the preclinical
      activity of a novel potent dual PI3K/mTOR inhibitor, PF-04691502, in five NPC
      cell lines: CNE-1, HK1, CNE-2, HONE-1 and C666-1, in which all of the cell lines
      possessed basal and activated expression of Akt and p70S6K. Over 80% inhibition
      of cell growth in all of these cell lines were achieved after 72 h of PF-04691502
      incubation and their IC50 were in hundred nanomolar range. CNE-2, HK1 and HONE-1
      were selected to further evaluate the effect of PF-04691502 on cell cycle,
      apoptosis and Akt downstream signaling. PF-04691502 induced G0/G1 cell cycle
      arrest and apoptosis at 24 h incubation and it significantly abrogated Akt and
      its downstream signaling by suppressing the expression of p-mTOR, p-p70S6K, p
      Akt(S473, T308), p-S6 and p-4E-BP1, suggesting its effectiveness in inhibition of
      translation and protein synthesis. Anti-proliferation was also observed in 3D
      culture system and spheroids formation of NPC cell line HONE-1-EBV was strongly
      inhibited by PF-04691502. Antitumor activity was observed in CNE-2 xenograft in 2
      weeks of 10 mg/kg PF-09641502 treatment to tumor bearing athymic nude mice. Both
      tumor volume and weight in treatment group were significantly lower than those in
      vehicle group while no obvious body weight decrease was found, suggesting this
      working dose was effective and well-tolerated. Additive effects were observed in
      combination of PF-09641502 with either cisplatin or paclitaxel. There were no
      synergistic effect observed in drug combination but PF-09641502 alone was
      effective in treating cisplatin resistant cell lines as compared to its parental
      control. The beneficial effects of PF-09641502 in both in vitro and in vivo
      studies for NPC warrant a further investigation.

PMID- 23975513
TI  - Genetic diversity of Rhodopirellula strains.
AB  - Rhodopirellula baltica SH1(T) is a marine planctomycete with 7,325 genes in its
      genome. Ten strains of the genus Rhodopirellula were studied in whole genome
      microarray experiments to assess the extent of their genetic relatedness to R.
      baltica SH1(T). DNA of strains which were previously affiliated with the species
      R. baltica (OTU A) hybridized with 3,645-5,728 genes of the type strain on the
      microarray. Strains SH398 and 6C (OTU B), representing a closely related species
      with an average nucleotide identity of 88 %, showed less hybridization signals:
      1,816 and 3,302 genes gave a hybridization signal, respectively. Comparative
      genomics of eight permanent draft genomes revealed the presence of over 4,000
      proteins common in R. baltica SH1(T) and strains of OTU A or B. The genus
      Rhodopirellula is characterized by large genomes, with over 7,000 genes per
      genome and a core genome of around 3000 genes. Individual Rhodopirellula strains
      have a large portion of strain-specific genes.

PMID- 23975514
TI  - Potential applications of gut microbiota to control human physiology.
AB  - The microorganisms living in our gut have been a black box to us for a long time.
      However, with the recent advances in high throughput DNA sequencing technologies,
      it is now possible to assess virtually all microorganisms in our gut including
      non-culturable ones. With the use of powerful bioinformatics tools to deal with
      multivariate analyses of huge amounts of data from metagenomics,
      metatranscriptomics, metabolomics, we now start to gain some important insights
      into these tiny gut inhabitants. Our knowledge is increasing about who they are,
      to some extent, what they do and how they affect our health. Gut microbiota have
      a broad spectrum of possible effects on health, from preventing serious diseases,
      improving immune system and gut health to stimulating the brain centers
      responsible for appetite and food intake control. Further, we may be on the verge
      of being capable of manipulating the gut microbiota by diet control to possibly
      improve our health. Diets consisting of different components that are fermentable
      by microbiota are substrates for different kinds of microbes in the gut. Thus,
      diet control can be used to favor the growth of some selected gut inhabitants.
      Nowadays, the gut microbiota is taken into account as a separate organ in human
      body and their activities and metabolites in gut have many physiological and
      neurological effects. In this mini-review, we discuss the diversity of gut
      microbiota, the technologies used to assess them, factors that affect microbial
      composition and metabolites that affect human physiology, and their potential
      applications in satiety control via the gut-brain axis. 

PMID- 23975515
TI  - Relationship between clinical data and gene expression in the HER2/ErbB2
      dependent signaling pathway in patients with acute heart failure.
AB  - Anticancer treatment with the human epidermal growth factor receptor (HER) 2
      inhibitors can lead to significant myocardial dysfunction. The primary aim of the
      study was to estimate the possible association between gene expression in the
      ErbB signaling pathway and selected clinical event data in patients with acute
      heart failure. Twenty-four patients (19 males), aged 68.6 +/- 12.3 years, were
      diagnosed and treated due to acute heart failure. The globaltest method was used
      for the correlation between blood nuclear cells' gene expression in the ErbB
      pathway (KEGG pathway id 04012) and important clinical data. Decreased expression
      of ErbB2/HER2 was found to be associated with the release of troponin and the
      need for inotropic support, whereas decreased neuregulin 1 (NRG1) expression was
      found to be associated with a decrease of ejection fraction below 40 %
      (globaltest p-value < 0.05). In summary, the ErbB signaling pathway and,
      especially, HER2/ErbB2 receptor expression are significantly associated with some
      of the recognized, clinically significant parameters of patients with acute heart
      failure. Evaluation of the molecular function of the HER2 receptor may be
      essential for the prognosis and targeted therapy of heart diseases. 

PMID- 23975516
TI  - Effects of the semi-dwarfing sdw1/denso gene in barley.
AB  - Recent advances in cereal genomics have made it possible to analyse the
      architecture of cereal genomes and their expressed components, leading to an
      increase in our knowledge of those genes that are associated with the key
      agronomical traits. Presently, use of a dwarfing gene in breeding process is
      crucial for the development of modern cultivars. In barley, more than 30 types of
      dwarfs or semi-dwarfs have been hitherto described. However, only a few of them
      have been successfully used in barley breeding programs. Both breeding and
      molecular mapping experiments were undertaken to enhance and evaluate the
      performance of semi-dwarf barley lines. The semi-dwarfing cultivars had improved
      lodging resistance and a higher harvest index. There have been a lot of
      investigations that have contributed new information to our basic understanding
      of the mechanisms underlying growth regulations in barley. This paper reviews
      semi-dwarfing genes in barley in general and special attention is paid to mapping
      of the sdw1/denso locus, changes in protein abundance and associations of the
      semi-dwarfness with gibberellins. 

PMID- 23975517
TI  - Alterations in alpha4beta2 nicotinic receptors in cognitive decline in
      Alzheimer's aetiopathology.
AB  - Nicotinic acetylcholine receptor subtype alpha4beta2 is considered important in
      the regulation of attention and memory, and cholinergic degeneration is known as
      one pathophysiology of Alzheimer's disease. Brain amyloid-beta protein deposition
      is also a key pathological marker of Alzheimer's disease. Recent amyloid-beta
      imaging has shown many cognitively normal subjects with amyloid-beta deposits,
      indicating a missing link between amyloid-beta deposition and cognitive decline.
      To date, the relationship between the alpha4beta2 nicotinic acetylcholine
      receptor and amyloid-beta burden has not been elucidated in vivo. In this study
      we investigated the relation between alpha4beta2 nicotinic acetylcholine receptor
      availability in the brain, cognitive functions and amyloid-beta burden in 20 non
      smoking patients with Alzheimer's disease at an early stage and 25 age-matched
      non-smoking healthy elderly adults by measuring levels of alpha4beta2 nicotinic
      acetylcholine receptor binding estimated from a simplified ratio method (BPRI)
      and Logan plot-based amyloid-beta accumulation (BPND) using positron emission
      tomography with alpha4beta2 nicotinic acetylcholine receptor tracer (18)F-2FA
      85380 and (11)C-Pittsburgh compound B. The levels of tracer binding were compared
      with clinical measures for various brain functions (general cognition, episodic
      and spatial memory, execution, judgement, emotion) using regions of interest and
      statistical parametric mapping analyses. Between-group statistical parametric
      mapping analysis showed a significant reduction in (18)F-2FA-85380 BPRI in the
      cholinergic projection region in patients with Alzheimer's disease with a variety
      of (11)C-Pittsburgh compound B accumulation. Spearman rank correlation analyses
      showed positive correlations of (18)F-2FA-85380 BPRI values in the medial frontal
      cortex and nucleus basalis magnocellularis region with scores of the Frontal
      Assessment Battery (a test battery for executive functions and judgement) in the
      Alzheimer's disease group (P < 0.05 corrected for multiple comparison), and also
      positive correlations of the prefrontal and superior parietal (18)F-2FA-85380
      BPRI values with the Frontal Assessment Battery score in the normal group (P <
      0.05 corrected for multiple comparison). These positive correlations indicated an
      in vivo alpha4beta2 nicotinic acetylcholine receptor role in those specific
      functions that may be different from memory. Both region of interest-based and
      voxelwise regression analyses showed a negative correlation between frontal (11)C
      Pittsburgh compound B BPND and (18)F-2FA-85380 BPRI values in the medial frontal
      cortex and nucleus basalis magnocellularis region in patients with Alzheimer's
      disease (P < 0.05 corrected for multiple comparison). These findings suggest that
      an impairment of the cholinergic alpha4beta2 nicotinic acetylcholine receptor
      system with the greater amount of amyloid deposition in the system plays an
      important role in the pathophysiology of Alzheimer's disease. 

PMID- 23975518
TI  - Comparable outcomes of partially matched related and matched related allogeneic
      hematopoietic cell transplantation following reduced-intensity conditioning in
      adult patients with Philadelphia chromosome-negative acute lymphoblastic
      leukemia.
AB  - Reports from multiple centers have shown that reduced-intensity allogeneic
      hematopoietic cell transplantation (RIC-HCT) is able to benefit some adult
      patients suffering from Philadelphia chromosome-negative acute lymphoblastic
      leukemia (ALL). However, the relationship between donor cell source and outcome
      of RIC-HCT in (Ph-)ALL patients has not been elucidated. In this study, we
      present the outcome of 57 (Ph-)ALL patients treated with reduced-intensity
      conditioning (RIC) followed by HCT from HLA-matched related (MRD, n = 34) or HLA
      partially matched related (PMRD, n = 23) donors from a multicenter cohort.
      Neutrophil recovery at day 100 occurred in 91.3 % of the PMRD group and 97.1 % of
      the MRD group (P = 0.84). One hundred days after treatment, the cumulative
      incidence of grade II-IV acute graft-versus-host disease (GVHD) was 30.4 % (95 %
      confidence interval [CI], 13.0-53.0 %) in patients who received PMRD grafts, and
      27.3 % (95 % CI, 15.0-48.0 %) for those who received MRD grafts (P = 0.76). The
      cumulative risk of developing chronic GVHD was 59.4 % (95 % CI, 31.0-72.0 %) in
      the MRD group and 23.4 % (95 % CI, 4.0-43.0 %) in the PMRD group (P = 0.03). The
      cumulative incidence of relapse in patients who received PMRD grafts was 18.8 %
      (95 % CI, 3.0-34.0 %), while for those who received MRD grafts it was 37.2 % (95
      % CI, 15.0-48.0 %) (P = 0.32). Overall treatment-related mortality was 41.6 % (95
      % CI, 20.0-62.0 %) in the PMRD group and 19.9 % (95 % CI, 7.0-35.0 %) in the MRD
      group (P = 0.08). Relapse was the most common cause of mortality in the MRD
      group, while infection contributed to the majority of deaths in the PMRD group.
      The 3-year probability of disease-free survival did not differ significantly
      between the two groups (55.5 % for the PMRD group vs. 48.4 % for the MRD group; P
      = 0.81). These data strongly suggest that RIC-HCT performed with PMRD may
      represent an alternative treatment option for adult patients with (Ph-)ALL.

PMID- 23975519
TI  - Are regimens containing rituximab effective in the initial treatment of Epstein
      Barr virus-positive natural killer cell lymphoproliferative disease-associated
      hemophagocytic lymphohistiocytosis?

PMID- 23975520
TI  - Multiple myeloma presenting as bilateral breast lumps in pregnant woman.
AB  - BACKGROUND: Multiple myeloma (MM) is a systemic disease in the elderly. Its
      incidence in patients younger than 40 years old and especially in pregnant women
      is extremely rare. MM may involve extraosseous sites, and only in rare cases it
      is observed in the breast. CASE REPORT: We describe the case of a 39-year-old
      woman diagnosed with an IgG lambda light-chain MM (Durie-Salmon stage IIIA,
      International Staging System II) in the 26th week of pregnancy, presenting with
      bilateral breast lumps. Dexamethasone (20 mg/m(2)/day on days 1-4, 9-12, and 17
      20) was given as an induction agent to decrease tumor mass during pregnancy.
      Adverse response to dexamethasone was minor with excellent tolerance. A healthy
      baby was delivered at week 34 of gestation. CONCLUSION: Breast nodules revealing
      MM are extremely rare. Clinical and radiological features are atypical.
      Presentation during pregnancy is extremely rare, making anti-MM treatment
      potentially challenging.

PMID- 23975521
TI  - Gait freezing and speech disturbance in Parkinson's disease.
AB  - Gait freezing and speech disturbance are disabling axial features of Parkinson's
      disease (PD). However, the pathogenesis of these features remains unclear. We
      investigated the relation between changes in gait freezing and speech disturbance
      using visual and auditory cues in PD. 18 PD patients, comprising of 9 patients
      with freezing (PDGF) and 9 without gait freezing were studied. Patients performed
      a 7-m back-and-forth walk in a baseline state and with visual and auditory cues.
      Gait velocity, stride length and cadence were evaluated using a three-dimensional
      gait analysis system. For speech evaluation, patients read ten sentences in a
      baseline state and with visual and auditory cues. The time delay of speech
      initiation, speech rate and the number of repetitions per sentence were
      quantified. In PDGF patients, the increase in gait velocity positively correlated
      with the decrease in the time delay of the speech initiation. Also, the increase
      in the gait velocity and cadence positively correlated with the decrease in the
      number of repetitions per sentence. The increase in the stride length positively
      correlated with the increase in speech rate. Lastly, the increase in stride
      length positively correlated with the decrease in the number of repetitions per
      sentence. These findings suggest that there is a common pathomechanism of gait
      freezing and speech disturbance in PD. 

PMID- 23975522
TI  - Prevalence of cerebrovascular disease: a door-to-door survey in West Anatolia.
AB  - The aim of this study was to demonstrate the prevalence of cerebrovascular
      disease (CVD), and its relation to age, education, gender, and other risk factors
      in the city of Denizli, Turkey. The study was performed between 2010 and 2011 in
      the city center, where 138,000 inhabitants >45 years were included in the
      research. 2,441 inhabitants were selected by cluster sampling method. A specific
      questionnaire about CVD was employed during the interview. We inquired about
      patient's age, gender, and educational history. If there was suspicion of CVD,
      cranial imaging was performed, and recent medical records were re-evaluated. The
      mean age was 58 +/- 10.1 (45-100) among 2,441 in this study. Of those, 1,257
      (51.5 %) participants were female and 1,184 (48.5 %) were male. We found the
      prevalence of CVD to be 0.9 % with 0.68 % among males and 1.21 % among females (p
      = 0.023). The mean age of subjects with CVD was 72.4 +/- 8.1 (56-86) years. CVD
      was found to increase with age (p = 0.001), but was lower than reported rates in
      other European countries; however, it was similar to that of Mediterranean
      countries. CVD was detected more frequently in women than men. This finding
      differed from other studies, but was first to evaluate the prevalence of CVD in
      Turkey.

PMID- 23975523
TI  - The use of University of Pennsylvania Smell Identification Test in the diagnosis
      of Parkinson's disease in Italy.
AB  - Hyposmia is a common finding in Parkinson's disease (PD). The 40-item University
      of Pennsylvania Smell Identification Test (UPSIT-40) has been adapted and
      administered in several countries as a diagnostic tool in the diagnosis of PD. We
      have developed a culturally adapted version of the UPSIT-40 and applied it to 61
      nondemented Italian controls and to 68 PD patients. Multiple linear regression
      analysis was performed to assess the factors that independently influence UPSIT
      40 and logistic regression analysis was employed to study the usefulness of UPSIT
      40 to predict PD diagnosis. Multiple linear regression analysis showed that PD
      diagnosis (p < 0.001), age (p = 0.006), gender (p = 0.003) and smoking status (p
      = 0.03) were significant independent predictors of the UPSIT-40 total score.
      Using diagnosis as dependent variable, logistic regression analysis showed that
      UPSIT-40 total score (p < 0.001) was an independent predictor of PD. Using a
      score <= 21/40 as a cut-off point for assigning subjects to PD group, the UPSIT
      40 total score differentiated PD and control subjects with 82 % sensitivity and
      88.2 % specificity. The adapted version of UPSIT-40 may be useful in addition to
      clinical examination to improve accuracy of diagnosis of PD in Italian
      population.

PMID- 23975524
TI  - [Occipital neuralgia: clinical and therapeutic characteristics of a series of 14
      patients].
AB  - INTRODUCTION. Occipital neuralgia is a pain in the distribution of the occipital
      nerves, accompanied by hypersensitivity to touch in the corresponding territory.
      AIMS. We present the occipital neuralgia series from the specialised headache
      unit at a tertiary hospital and analyse its clinical characteristics and its
      response to therapy. PATIENTS AND METHODS. Variables were collected from the
      cases of occipital neuralgia diagnosed in the above-mentioned headache unit
      between January 2008 and April 2013. RESULTS. A series of 14 patients (10
      females, 4 males) with occipital neuralgia was obtained out of a total of 2338
      (0.59%). Age at onset of the clinical signs and symptoms: 53.4 +/- 20.3 years
      (range: 17-81 years) and time elapsed to diagnosis was 35.5 +/- 58.8 months
      (range: 1-230 months). An intracranial or cervical pathology was ruled out by
      suitable means in each case. Baseline pain of a generally oppressive nature and
      an intensity of 5.3 +/- 1.3 (4-8) on the verbal analogue scale was observed in 13
      of them (92.8%). Eleven (78.5%) presented exacerbations, generally stabbing
      pains, a variable frequency (4.6 +/- 7 a day) and an intensity of 7.8 +/- 1.7
      (range: 4-10) on the verbal analogue scale. Anaesthetic blockade was not
      performed in four of them (two due to a remitting pattern and two following the
      patient's wishes); in the others, blockade was carried out and was completely
      effective for between two and seven months. Four cases had previously received
      preventive treatment (amitriptyline in three and gabapentin in one), with no
      response. CONCLUSIONS. In this series from a specialised headache unit, occipital
      neuralgia is an infrequent condition that mainly affects patients over 50 years
      of age. Given its poor response to preventive treatment, the full prolonged
      response to anaesthetic blockades must be taken into account.

PMID- 23975525
TI  - [Baroreflex behavior in patients with vasovagal syncope during active standing].
AB  - INTRODUCTION. Neurally-mediated syncope, also known as vasovagal syncope, is
      defined as sudden and transient loss of consciousness due to a sudden and deep
      fall in arterial pressure. AIM. To determine the differences on the hemodynamic
      parameters mediating the baroreflex during active standing in patients with
      clinical diagnosis of vasovagal syncope as well as in healthy subjects. SUBJECTS
      AND METHODS. Cross-sectional, observational and comparative study. We included 20
      patients diagnosed with neurally-mediated syncope and 30 controls, who underwent
      active orthostatic test, recording by finometry the systolic blood pressure (SBP)
      and heart rate (interbeat interval) in a continuous (beat to beat) and
      noninvasive fashion. RESULTS. Patients with syncope had a mean supine baseline
      SBP significantly higher than that of the healthy controls. The measured values
      of SBP from baseline showed a significant difference between groups, being also
      lower in the control group. No differences were found between groups in the fall
      of SBP from the first peak of heart rate to the trough. The recovery time of the
      SBP to the baseline was no different in controls and in patients. CONCLUSIONS.
      The baseline SBP and SBP drop measured from baseline in supine position was
      higher in patients than in healthy subjects. The magnitude of the elevation of
      heart rate has a tendency to be higher in the patient group compared with the
      control group. This suggests a sympathetic hyperactivity in patients with
      syncope. 

PMID- 23975526
TI  - [Fractures in spinal muscular atrophy].
AB  - AIM: To determine the frequency of fractures in patients with spinal muscular
      atrophy, their mechanism of production, age at appearance and functional
      repercussions. PATIENTS AND METHODS: Sixty-five patients with spinal muscular
      atrophy were studied. Cases of fractures diagnosed by means of X-rays were
      collected and the following parameters were analysed: type of spinal muscular
      atrophy, gait, age at the time the fracture occurred, mechanism of production,
      location, treatment applied and functional repercussion. RESULTS: Thirteen
      patients (20%) presented a total of 20 fractures (four of them presented two or
      more fractures). The mean age was 6.35 years. The fractures were mostly located
      in the femur and the mechanism of production was falls in 12 cases and minor
      traumatic injury in eight. No vertebral fractures were detected. All of them were
      treated conservatively. The only patient with a fracture who was able to walk
      stopped walking after immobilisation. CONCLUSIONS: The existence of fractures in
      these patients interferes with their quality of life and their level of
      functioning. It is important to prevent them from occurring during management of
      the patient and by ensuring a correct posture in the wheelchair with the use of
      restraint systems. Further studies are needed on the loss of bone mineral density
      in these patients and their possible relationship with fractures.

PMID- 23975527
TI  - [Alternating hemiplegia of childhood. The first clinical case reported in El
      Salvador].
AB  - INTRODUCTION: Alternating hemiplegia of childhood (AHC) is a rare disease
      characterised by repeated episodes of hemiplegia that alternately affect one side
      of the body. Onset is usually before the age of 18 months, the episodes last
      anywhere from a few minutes to several days. In some cases these episodes may
      even render the early infant quadriplegic for some time if one begins before the
      previous one has finished or if they occur at the same time. The clinical
      description includes, in addition to these paralysing attacks, other paroxysmal
      manifestations that are present in practically all the children diagnosed with
      this condition and which, moreover, appear earlier. Such manifestations consist
      in tonic attacks, dystonic attacks, abnormal eye movements and autonomic
      disorders. The fact that these symptoms precede the typical clinical signs and
      symptoms often leads to delays in the final diagnosis. CASE REPORT: We report the
      case of a male, aged one year and nine months, who initially presented a clinical
      picture of tonic seizures at the age of two weeks, which then went on to episodes
      of hemiplegia that appeared alternately at the age of 11 months. The patient also
      presented retarded overall psychomotor development. In the early stages of the
      symptoms he was diagnosed with epilepsy, failed to respond to multiple
      antiepileptic drugs, and the electroencephalogram, neuroimaging and complementary
      blood and urine tests were all normal/negative. The patient responded well to
      flunarizine. CONCLUSIONS: This is the first patient with AHC reported in El
      Salvador. The early and accurate diagnosis of AHC is essential to be able to
      establish drug therapy and improve the prognosis and the quality of life of
      patients and their families.

PMID- 23975528
TI  - Review of the novelties presented at the 28th Congress of the European Committee
      for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I).
AB  - The most relevant data presented at the 28th edition of the European Committee
      for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2012
      in France, have been summarized in the fifth edition of the Post-ECTRIMS Expert
      Meeting held in Madrid in October 2012. The present review summarizes the views
      and results of the meeting and is being published in three parts. This first part
      of the Post-ECTRIMS review addresses the incidence and prevalence of multiple
      sclerosis (MS), which has increased at the global level, largely due to the
      increased incidence in women because the risk of developing the disease is
      increased in females, with minimal concurrent effect on the progression of MS.
      Sexual dimorphism is evident in MS, and all evidence points to an interaction
      between hormonal, genetic, and environmental factors. The paediatric population
      represents an ideal group to study susceptibility factors to the disease, which
      is why collaborative studies designed to increase the patient samples are being
      considered, given its low prevalence. In this review, inflammatory and
      neurodegenerative phenomena involved in the pathogenesis of the disease and that
      have a cause-and-effect or shared relationship with the disease are being
      discussed. Current hypotheses suggest a phenomenon of compartmentalization,
      presumably inaccessible to current immunomodulatory therapy. Among the possible
      mechanisms involved in these processes of inflammation and demyelination, the
      role of Th17 cells, mitochondrial dysfunction, early disruption of astrocytic
      processes, and chronic hypoxia are discussed. 

PMID- 23975529
TI  - [Neurons and values].
AB  - This article examines the advances made by neuroscience in the attempt to find an
      answer to the question regarding the origin and foundation of moral judgements
      and of human behaviour in compliance with them. The conception of the brain as
      something dynamic and capable of adapting to the social and cultural surroundings
      is seen to be an important point for philosophy. At the same time, the complexity
      of ethical issues that cannot be reduced to observations based strictly on
      neurons alone also becomes quite apparent. Nevertheless, scientists and
      philosophers should get together and communicate with one another so as to be
      able to pose their questions with greater rigour and take advantage of each
      other's respective knowledge. 

PMID- 23975531
TI  - [Ethical deliberations on genetic testing in children and adolescents].

PMID- 23975532
TI  - [Kinetogenic reflex epilepsy associated to masturbatory movements].

PMID- 23975535
TI  - Protective effects of N-acetylcysteine on 3, 4-methylenedioxymethamphetamine
      induced neurotoxicity in male Sprague-Dawley rats.
AB  - Exposure to 3, 4-methylenedioxymethamphetamine (MDMA) leads to spatial memory
      impairment and hippocampal cell death. In the present study we have examined the
      protective effects of N-acetyl-L-cysteine (NAC) on MDMA-induced neurotoxicity. A
      total of 56 male Sprague Dawley rats (200-250 g) received twice daily
      intraperitoneal (IP) injections of 5, 10 or 20 mg/kg MDMA plus NAC (100 mg/kg).
      Rectal temperatures were recorded before and after daily treatment. We used a
      Morris water maze (MWM) to assess spatial learning and memory. At the end of the
      study rats' brains were removed, cells were counted and the level of Bcl-2, Bax
      and caspase-3 expression in the hippocampi were measured. NAC pretreatment
      significantly reduced MDMA-induced hyperthermia. In the MWM, NAC significantly
      attenuated the MDMA-induced increase in distance traveled; however the observed
      increase in escape latency was not significant. The decrease in time spent in the
      target quadrant in MDMA animals was significantly attenuated (p < 0.001, all
      groups). NAC protected against MDMA-induced cell death and the up -regulation of
      Bax and Caspase-3, in addition to the down-regulation of Bcl-2. This data
      suggested a possible benefit of NAC in the treatment of neurotoxicity among those
      who use MDMA. 

PMID- 23975536
TI  - The preventive effect of NR2B and NR2D-containing NMDAR antagonists on Abeta
      induced LTP disruption in the dentate gyrus of rats.
AB  - Amyloid beta-protein (Abeta) in the brain of Alzheimer's disease (AD) potently
      inhibits the synaptic plasticity subsequently causing the cognitive deficits.
      Long-term potentiation (LTP) of synaptic transmission is thought to be an
      important cellular mechanism underlying memory formation. Different NR2 subunits
      are involved in NMDA receptor-dependent LTP. In the present study, we
      investigated the roles of NR2B and NR2D-containing NMDAR on Abeta(1-42)-induced
      LTP deficits in the hippocampal slices of rats by using selective NMDAR
      antagonists. First, we found that Abeta(1-42) significantly inhibited the LTP in
      the dentate gyrus of slices as reported before. Following that the Abeta(1-42)
      induced LTP inhibition was prevented by the pre-perfusion of the specific NR2B
      containing NMDAR antagonists ifenprodil (approximately >200-fold selectivity for
      NR2B) and Ro25-6981 (>3,000-fold selectivity for NR2B), as well as PPDA, a
      specific NR2D receptor antagonist. Meanwhile, the antagonists on their own had no
      or only partial effects on the normal LTP in the same dose condition. These
      findings not only support the effects of NR2B and NR2D subunits on Abeta(1-42)
      induced LTP deficits, but also imply that preferentially targeting NR2B- and NR2D
      containing NMDARs may provide an effective means to prevent cognitive deficits in
      the early AD. 

PMID- 23975537
TI  - Depression in older patients with advanced colorectal cancer is closely connected
      with immunosuppressive acidic protein.
AB  - Colorectal cancer (CRC) is one of the most common tumors. CRC patients are
      susceptible to suffering from depression. Whether the immune system of CRC
      patients with depression is impaired or stimulated is controversial. Possible
      reasons for this conflict are the involvement of confounding factors, such as the
      age of the patient, the stage of the CRC and the types of treatment in previous
      studies. To demonstrate clearly the relationship between depression and the
      immune system in the context of CRC, the present study included only older
      patients with advanced CRC who received only chemotherapy, and the study adopted
      immunosuppressive acidic protein (IAP) as an immune parameter for the first time.
      A total of 56 older patients with advanced CRC completed the Zung Self-Rating
      Depression Scale (SDS) and were divided into two groups according to SDS scores.
      The patients exhibiting depression were treated with fluoxetine until their
      symptoms remitted. The serum levels of IAP and the percentages of CD3-positive
      (CD3+), CD4+, CD8+ T lymphocytes and CD56+ natural killer (NK) cells and
      Neutrophil-lymphocyte ratio (NLR) were calculated at the time of enrollment and
      once the symptoms remitted. Correlation analyses revealed that the SDS score was
      positively associated with serum IAP levels but negatively associated with CD3
      and CD4 levels. Among the depressed and non-depressed patients, serum IAP levels
      and the percentages of CD3 and CD4 cells were dramatically different. After the
      depression symptoms were treated, the IAP levels dramatically decreased, while
      the levels of CD3, CD4, CD8 and CD56 were unchanged. All of above suggested that
      IAP was closely correlated with depression and might be a relatively objective
      parameter for predicting depression. 

PMID- 23975538
TI  - Increased fitness and realized heritability in emamectin benzoate-resistant
      Chrysoperla carnea (Neuroptera: Chrysopidae).
AB  - The common green lacewing Chrysoperla carnea is a key biological control agent
      employed in integrated pest management (IPM) programs for managing various insect
      pests. A field collected population of C. carnea was selected for emamectin
      benzoate resistance in the laboratory and fitness costs and realized heritability
      were investigated. After five generations of selection with emamectin benzoate,
      C. carnea developed a 318-fold resistance to the insecticide. The resistant
      population had a relative fitness of 1.49, with substantially higher emergence
      rate of healthy adults, fecundity and hatchability and shorter larval duration,
      pupal duration, and development time compared to the susceptible population. Mean
      population growth rates; such as the intrinsic rate of natural population
      increase and biotic potential were higher for the emamectin benzoate selected
      population compared to the susceptible population. The realized heritability
      (h(2)) value of emamectin benzoate resistance was 0.34 in emamectin benzoate
      selected population of C. carnea. Chrysoperla species which show resistance to
      insecticides makes them compatible with those IPM systems where emamectin
      benzoate is employed.

PMID- 23975539
TI  - The toxicity of silver nanoparticles to zebrafish embryos increases through
      sewage treatment processes.
AB  - Silver nanoparticles (AgNPs) are widely believed to be retained in the sewage
      sludge during sewage treatment. The AgNPs and their derivatives, however, re
      enter the environment with the sludge and via the effluent. AgNP were shown to
      occur in surface water, while evidence of a potential toxicity of AgNPs in
      aquatic organisms is growing. This study aims to examine the toxicity of AgNPs to
      the embryos of the aquatic vertebrate model zebrafish (Danio rerio) before and
      after sewage treatment plants (STPs) processes. Embryos were treated with AgNP
      (particle size: >90 % <20 nm) and AgNO3 in ISO water for 48 h and consequently
      displayed effects such as delayed development, tail malformations and edema. For
      AgNP, the embryos were smaller than the controls with conspicuously smaller yolk
      sacs. The corresponding EC50 values of 48 hours post fertilization (hpf) were
      determined as 73 MUg/l for AgNO3 and 1.1 mg/l for AgNP. Whole-mount
      immunostainings of primary and secondary motor neurons also revealed secondary
      neurotoxic effects. A TEM analysis confirmed uptake of the AgNPs, and the
      distribution within the embryo suggested absorption across the skin. Embryos were
      also exposed (for 48 h) to effluents of AgNP-spiked model STP with AgNP influent
      concentrations of 4 and 16 mg/l. These embryos exhibited the same malformations
      than for AgNO3 and AgNPs, but the embryo toxicity of the sewage treatment
      effluent was higher (EC50 = 142 MUg/l; 48 hpf). On the other hand, control STP
      effluent spiked with AgNPs afterwards was less toxic (EC50 = 2.9 mg/l; 48 hpf)
      than AgNPs in ISO water. This observation of an increased fish embryo toxicity of
      STP effluents with increasing AgNP influent concentrations identifies the
      accumulation of AgNP in the STP as a potential source of effluent toxicity.

PMID- 23975540
TI  - Changes in the prevalence of hypothyroidism: the HUNT Study in Norway.
AB  - OBJECTIVE: Untreated hypothyroidism is common in iodine-replete areas. Frequent
      thyroid function testing and use of levothyroxine treatment for subclinical
      hypothyroidism suggest that the prevalence may have decreased. Therefore, in this
      study, we examined changes in the prevalence of hypothyroidism in a Norwegian
      county from 1995-1997 to 2006-2008. DESIGN: Population surveys of 33,917
      individuals in 1995-1997 and 49,180 individuals in 2006-2008 were carried out.
      METHODS: We compared the prevalence of untreated overt, untreated subclinical,
      and treated hypothyroidism between 1995-1997 and 2006-2008. RESULTS: The
      prevalence of untreated overt hypothyroidism among women decreased by 84% from
      1995-1997 (0.75%) to 2006-2008 (0.12%) (prevalence ratio (PR) 0.16; 95% CI 0.10
      0.26). The corresponding decrease among men was 43% from 0.21 to 0.12% (PR 0.57;
      95% CI 0.28-1.16). The prevalence of untreated subclinical hypothyroidism
      decreased by 64% from 3.0 to 1.1% in women (PR 0.36; 95% CI 0.31-0.42) and
      decreased by 54% from 2.1 to 1.0% in men (PR 0.46; 95% CI 0.38-0.56). Conversely,
      the prevalence of treated hypothyroidism among women increased by 60% from 5.0 to
      8.0% (PR 1.60, 95% CI 1.50-1.71), and the corresponding prevalence in men doubled
      from 1.0 to 2.0% (PR 1.96; 95% CI 1.59-2.41). The prevalence of any form of
      hypothyroidism remained essentially similar at 9% in women and 3% in men.
      CONCLUSIONS: The prevalence of untreated hypothyroidism in this Norwegian county
      decreased strongly from 1995-1997 to 2006-2008. The findings suggest that the
      prevalence of untreated hypothyroidism in populations with easy access to thyroid
      function testing and levothyroxine treatment may now be low.

PMID- 23975542
TI  - Article retracted, but the message lives on.
AB  - The retraction of an original article aims to ensure that readers are alerted to
      the fact that the findings are not trustworthy. However, the present research
      suggests that individuals still believe in the findings of an article even though
      they were later told that the data were fabricated and that the article was
      retracted. Participants in a debriefing condition and a no-debriefing condition
      learned about the scientific finding of an empirical article, whereas
      participants in a control condition did not. Afterward, participants in the
      debriefing condition were told that the article had been retracted because of
      fabricated data. Results showed that participants in the debriefing condition
      were less likely to believe in the findings than participants in the no
      debriefing condition but were more likely to believe in the findings than
      participants in the control condition, suggesting that individuals do adjust
      their beliefs in the perceived truth of a scientific finding after debriefing-but
      insufficiently. Mediational analyses revealed that the availability of generated
      causal arguments underlies belief perseverance. These results suggest that a
      retraction note of an empirical article in a scientific journal is not sufficient
      to ensure that readers of the original article no longer believe in the article's
      conclusions.

PMID- 23975541
TI  - Negative mood and alcohol problems are related to respiratory dynamics in young
      adults.
AB  - This study examined the relationship of negative affect and alcohol use behaviors
      to baseline respiration and respiratory response to emotional challenge in young
      adults (N = 138, 48 % women). Thoracic-to-abdominal ratio, respiratory frequency
      and variability, and minute volume ventilation were measured during a low-demand
      baseline task, and emotional challenge (viewing emotionally-valenced, emotionally
      neutral, and alcohol-related pictures). Negative mood and alcohol problems
      principal components were generated from self-report measures of negative affect
      and mood, alcohol use, and use-related problems. The negative mood component was
      positively related to a thoracic bias when measured throughout the study
      (including baseline and picture exposure). There was generally greater
      respiratory activity in response to the picture cues, although not specifically
      in response to the content (emotional or alcohol-related) of the picture cues.
      The alcohol problems component was positively associated with respiratory
      reactivity to picture cues, when baseline breathing patterns were controlled.
      Self-report arousal data indicated that higher levels of negative mood, but not
      alcohol problems, were associated with greater arousal ratings overall. However,
      those with alcohol problems reported greater arousal to alcohol cues, compared to
      emotionally neutral cues. These results are consistent with theories relating
      negative affect and mood to breathing patterns as well as the relationship
      between alcohol problems and negative emotions, suggesting that the use of
      respiratory interventions may hold promise for treating problems involving
      negative affect and mood, as well as drinking problems.

PMID- 23975543
TI  - Exercise reduces cellular stress related to skeletal muscle insulin resistance.
AB  - This study sought to evaluate the effects of a single session of exercise on the
      expression of Hsp70, of c-jun N-terminal kinase (JNK), and insulin receptor
      substrate 1 serine 612 (IRS(ser612)) phosphorylation in the skeletal muscle of
      obese and obese insulin-resistant patients. Twenty-seven volunteers were divided
      into three experimental groups (eutrophic insulin-sensitive, obese insulin
      sensitive, and obese insulin-resistant) according to their body mass index and
      the presence of insulin resistance. The volunteers performed 60 min of aerobic
      exercise on a cycle ergometer at 60 % of peak oxygen consumption. M. vastus
      lateralis samples were obtained before and after exercise. The protein
      expressions were evaluated by Western blot. Our findings show that compared with
      paired eutrophic controls, obese subjects have higher basal levels of p-JNK (100
      +/- 23 % vs. 227 +/- 67 %, p = 0.03) and p-IRS-1(ser612) (100 +/- 23 % vs. 340 +/
      67 %, p < 0.001) and reduced HSP70 (100 +/- 16 % vs. 63 +/- 12 %, p < 0.001).
      The presence of insulin resistance results in a further increase in p-JNK (460 +/
      107 %, p < 0.001) and a decrease in Hsp70 (46 +/- 5 %, p = 0.006), but p-IRS
      1(ser612) levels did not differ from obese subjects (312 +/- 73 %, p > 0.05).
      Exercise reduced p-JNK in obese insulin-resistant subjects (328 +/- 33 %, p =
      0.001), but not in controls or obese subjects. Furthermore, exercise reduced p
      IRS-1(ser612) for both obese (122 +/- 44 %) and obese insulin-resistant (185 +/-
      36 %) subjects. A main effect of exercise was observed in HSP70 (p = 0.007). We
      demonstrated that a single session of exercise promotes changes that characterize
      a reduction in cellular stress that may contribute to exercise-induced increase
      in insulin sensitivity. 

PMID- 23975544
TI  - AKR1B10 is induced by hyperglycaemia and lipopolysaccharide in patients with
      diabetic nephropathy.
AB  - Aldose reductase family member B10 (AKR1B10) belongs to the aldo-keto reductase
      gene superfamily and is closely related to aldose reductase (AKR1B1). It has been
      shown that AKR1B10 is present in many of the same human tissues as AKR1B1. The
      objective of this study was to investigate whether AKR1B10 has a role in diabetic
      nephropathy (DN) by investigating its response to high glucose and inflammation,
      both of which have been associated with the development and progression of DN.
      Expression levels of AKR1B10 were determined in peripheral blood mononuclear
      cells (PBMCs) obtained from 25 patients with type 1 diabetes and nephropathy, 25
      without DN and 25 normal healthy controls that were exposed to high glucose (25
      mM D-glucose) and also the inflammatory stressor lipopolysaccharide (LPS, 10
      MUm). Under high glucose and LPS conditions, there was a significant increase in
      the expression of AKR1B10 in the PBMCs from patients with DN compared to those
      without DN and the normal controls. In conclusion, these results suggest that
      AKR1B10 may have an important role in the development and progression of DN. 

PMID- 23975545
TI  - Epidemic increase in Salmonella bloodstream infection in children, Bwamanda, the
      Democratic Republic of Congo.
AB  - Salmonella enterica is the leading cause of bloodstream infection in children in
      sub-Saharan Africa, but few data are available from Central-Africa. We documented
      during the period November 2011 to May 2012 an epidemic increase in invasive
      Salmonella bloodstream infections in HGR Bwamanda, a referral hospital in
      Equateur Province, DR Congo. Salmonella spp. represented 90.4 % (103 out of 114)
      of clinically significant blood culture isolates and comprised Salmonella
      Typhimurium (54.4 %, 56 out of 103), Salmonella Enteritidis (28.2 %, 29 out of
      103) and Salmonella Typhi (17.5 %, 18 out of 103), with Salmonella Enteritidis
      accounting for most of the increase. Most (82 out of 103, 79.6 %) isolates were
      obtained from children < 5 years old. Median ages of patients infected with
      Salmonella Typhimurium and Salmonella Enteritidis were 14 months (14 days to 64
      years) and 19 months (3 months to 8 years) respectively. Clinical presentation
      was non-specific; the in-hospital case fatality rate was 11.1 %. More than two
      thirds (69.7 %, 53 out of 76) of children < 5 years for whom laboratory data were
      available had Plasmodium falciparum infection. Most (83/85, 97.6 %) non-typhoid
      Salmonella isolates as well as 6/18 (33.3 %) Salmonella Typhi isolates were
      multidrug resistant (i.e. resistant to the first-line oral antibiotics
      amoxicillin, trimethoprim-sulfamethoxazole and chloramphenicol), one (1.0 %)
      Salmonella Typhimurium had decreased ciprofloxacin susceptibility owing to a
      point mutation in the gyrA gene (Gly81Cys). Multilocus variable-number tandem
      repeat (MLVA) analysis of the Salmonella Enteritidis isolates revealed closely
      related patterns comprising three major and four minor profiles, with differences
      limited to one out of five loci. These data show an epidemic increase in clonally
      related multidrug-resistant Salmonella bloodstream infection in children in DR
      Congo.

PMID- 23975553
TI  - Metal contamination recorded in the sediment of the semi-closed Bakar Bay
      (Croatia).
AB  - This study presents metal levels in the sediments of the Bakar Bay, with its main
      goal to evaluate recent anthropogenic influence, as well as over previous
      decades. Sediment profiles at 7 sampling points were taken. Chemical contents in
      bulk sediment were obtained using ICP, ICP-MS, and AAS methodologies, and 20 most
      significant elements were presented. Concentrations of selected elements were
      evaluated by factor statistical analyses to identify their source. Also, metal
      enrichment factor and geoaccumulation index were calculated, and spatial
      distribution maps for three sediment layers were constructed. Measured metal
      concentrations in sediment were compared with concentrations in other sediments
      from the Adriatic Sea. In addition, a set of sediment quality guidelines were
      also applied in order to predict the probability of adverse biological effects on
      the benthic community: This was found not to be very serious. Factor analysis
      clearly demonstrates the segregation between metals of natural origin resulted
      from soil and bedrock weathering (Li, Al, Cr, Sc), and with two anthropogenic
      sources originating from the city of Bakar and bulk cargo terminal (Hg, Pb, Zn,
      Ag, Sn, and Fe). Mercury (max 0.65 MUg g(-1)) is found to be the heaviest
      contaminant, followed by lead (max 71.5 MUg g(-1)), copper (89.3 MUg g(-1)), and
      zinc (156 MUg g(-1)). However, this study shows that Bakar Bay is considerably
      less polluted with toxic metals than it was believed. 

PMID- 23975554
TI  - Geochemical records of environmental changes.

PMID- 23975555
TI  - Occupational exposure to anti-cancer drugs: A review of effects of new
      technology.
AB  - Because anti-cancer drugs are non-selective, they affect both cancerous and non
      cancerous cells. Being carcinogenic and mutagenic, many anticancer drugs
      therefore present a major health risk to healthcare staff working with them. This
      paper reviews the means by which exposure to anti-cancer drugs in the workplace
      may be monitored, assessed and reduced. Both biological monitoring, using non
      selective methods or compound-selective methods, and environmental monitoring
      have provided information on the nature and degree of exposure in the workplace.
      Pharmaceutical isolators, used for the compounding of cytotoxic IV infusions and
      the preparation of injectable drugs, provide a physical barrier between
      pharmacists and cytotoxic drugs and reduce direct exposure. However, the interior
      of isolators and the contents thereof (e.g. infusion bags and syringes) are
      readily contaminated by aerosols and spillages and afford a secondary source of
      exposure to pharmacists, nurses and cleaning staff. Closed system transfer
      devices (CSTDs), designed to prohibit the transfer of contaminants into the
      working environment during drug transfer between the vial and syringe, have been
      successful in further reducing, but not eliminating surface contamination. Given
      that the number of patients requiring treatment with chemotherapeutic agents is
      predicted to increase, further efforts to reduce occupational exposure to anti
      cancer drugs, including the refinement and wider use of CTSDs, are recommended. 

PMID- 23975556
TI  - Cost savings realized by use of the PhaSeal((r)) closed-system transfer device
      for preparation of antineoplastic agents.
AB  - PURPOSE: Medication cost is a major factor associated with increasing health care
      costs in the United States. Expenditures for prescription drugs in 2013 are
      estimated to be $283.7 billion. Closed system transfer devices are widely used
      for preparation of hazardous drugs. Reports indicate the Phaseal((r)) closed
      system transfer device maintains sterility in vials for 7 days, suggesting the
      unused portion of single-use vials could be salvaged. This study was done to
      determine whether using a closed system transfer device to extend the beyond-use
      date of single-use vials of antineoplastic medications would result in a
      measurable cost saving. METHODS: A list of 25 drugs available in single-use
      vials, with a chemical stability of at least 48 hours, was compiled. Use of these
      agents was recorded during a 50-day period in April through June 2012. Use from a
      total of 296 vials of 21 antineoplastic agents was recorded. After allowing for
      the initial use of each vial, the mean potential percentage of drug waste was
      calculated to be 57.03%. RESULTS: Actual savings during the study period was
      $96,348.70. The pharmacy avoided nearly half of the potential waste and saved a
      mean of 29% of each vial. The cost-saving during the study period represents a
      $703,047.67 annual saving; which more than offsets the $106,556.55 the pharmacy
      spent for the Phaseal((r)) system in 2012. CONCLUSION: In addition to being a
      protective measure to reduce exposure to hazardous agents, use of the
      Phaseal((r)) system results in a reduction in drug waste, and a noticeable cost
      saving for antineoplastic agents.

PMID- 23975557
TI  - Esomeprazole-induced irritability.

PMID- 23975558
TI  - Cerebral venous thrombosis and Buerger's disease.

PMID- 23975559
TI  - Predictive ability of C-reactive protein for early mortality after ischemic
      stroke: comparison with NIHSS score.
AB  - We aimed to compare the association of high-sensitivity C-reactive protein (CRP)
      and National Institutes of Health Stroke Scale (NIHSS) score with mortality risk
      and to determine the optimal threshold of CRP for prediction of mortality in
      ischemic-stroke patients. A series of 162 patients with first-ever ischemic
      stroke admitted within 24 h after onset of symptoms was enrolled. CRP and NIHSS
      score were estimated on admission and their predictive abilities for mortality at
      7 days were determined by logistic-regression analyses. Receiver-Operating
      Characteristic (ROC) curves were depicted to identify the optimal cut-off of CRP,
      using the maximum Youden-index and the shortest-distance methods. Deceased
      patients had higher levels of CRP and NIHSS on admission (8.87 +/- 7.11 vs. 2.20
      +/- 4.71 mg/l for CRP, and 17.31 +/- 6.36 vs. 8.70 +/- 4.85 U for NIHSS,
      respectively, P < 0.01). CRP and NIHSS were correlated with each other (r (2) =
      0.39, P < 0.001) and were also independently associated with increased risk of
      mortality [odds ratios (95 % confidence interval) of 1.16 (1.05-1.28) and 1.20
      (1.07-1.35) for CRP and NIHSS, respectively, P < 0.01]. The areas under the ROC
      curves of CRP and NIHSS for mortality were 0.82 and 0.84, respectively. The CRP
      value of 2.2 mg/l was identified as the optimal cut-off value for prediction of
      mortality within 7 days (sensitivity: 0.81, specificity: 0.80). Thus, CRP as an
      independent predictor of mortality following ischemic-stroke is comparable with
      NIHSS and the value of 2.2 mg/l yields the optimum sensitivity and specificity
      for mortality prediction.

PMID- 23975560
TI  - Effect of low-frequency stimulation on kindling induced changes in rat dentate
      gyrus: an ultrastructural study.
AB  - It has been shown that low-frequency stimulation (LFS) can induce anticonvulsant
      effects. In this study, the effect of different LFS frequencies on kindling
      induced behavioral and ultrastructural changes was investigated. For induction of
      kindled seizures in rats, stimulating and recording electrodes were implanted in
      perforant path and dentate gyrus, respectively. Animals were stimulated in a
      rapid kindling manner. Different groups of animals received LFS at different
      frequencies (0.5, 1 and 5 Hz) following kindling stimulations and their effects
      on kindling rate were determined using behavioral and ultrastructural studies.
      Kindling stimulations were applied for 7 days. Then, the animals were sacrificed
      and their dentate gyrus was sampled for ultrastructural studies under electron
      microscopy. All three used LFS frequencies (0.5, 1 and 5 Hz) had a significant
      inhibitory effect on kindling rate and decreased afterdischarge duration and the
      number of stimulations to achieve stage 4 and 5 seizures significantly. In
      addition, application of LFS prevented the increase in the post-synaptic density
      and induction of concave synaptic vesicles following kindling. There was no
      significant change between anticonvulsant effects of LFS at different
      frequencies. Obtained results show that LFS application can prevent the neuronal
      hyperexcitability by preventing the ultrastructural changes during kindling and
      this may be one of the mechanisms of LFS anticonvulsant effects.

PMID- 23975561
TI  - Brainstem somatosensory and auditory evoked responses in central pontine
      myelinolysis.

PMID- 23975562
TI  - Pioneers in migration, pioneering in dementia: first generation immigrants in a
      European metropolitan memory clinic.
AB  - By reviewing the clinical files of 1,058 consecutive newly admitted outpatients
      of a Brussels-based memory clinic between 2005 and 2012, this study aims to
      document the demographic and clinical characteristics of European and non
      European first generation immigrants. They accounted for 18.6% of the patients,
      of which 8.6% came from outside Europe (mostly from Morocco, Turkey and the
      Democratic Republic of Congo). Immigrants with AD tended to be younger, and there
      was a higher proportion of males among non-European ethnic minorities. There was
      a higher proportion of Parkinson-related cognitive disorders and Lewy Body
      disease among European immigrants, whereas non-Europeans had more often a
      psychiatric diagnosis. Even after correction for education, non-European
      immigrants had lower MMSE scores, and they did report longer delays between first
      symptoms and diagnosis, although this last difference was not statistically
      significant. These results suggest that non-European immigrants with cognitive
      problems consult later.

PMID- 23975563
TI  - Evidence of lumpy skin disease virus over-wintering by transstadial persistence
      in Amblyomma hebraeum and transovarial persistence in Rhipicephalus decoloratus
      ticks.
AB  - Lumpy skin disease is a debilitating cattle disease caused by the lumpy skin
      disease virus (LSDV), belonging to the genus Capripoxvirus. Epidemics of the
      disease usually occur in summer, when insect activity is high. Limited
      information is available on how LSDV persists during inter-epidemic periods.
      Transmission of LSDV by mosquitoes such as Aedes aegypti has been shown to be
      mechanical, there is no carrier state in cattle and the role of wildlife in the
      epidemiology of the disease seems to be of minor importance. Recent studies in
      ticks have shown transstadial persistence of LSDV in Rhipicephalus appendiculatus
      and Amblyomma hebraeum as well as transovarial persistence of the virus in
      Rhipicephalus decoloratus, R. appendiculatus and A. hebraeum. The over-wintering
      of ticks off the host as part of their life cycles is well known: A. hebraeum and
      R. appendiculatus over-winter, for example, on the ground as engorged
      nymphs/unfed (emergent) adults while R. decoloratus over-winters on the ground as
      engorged females. In this study, transstadial and transovarial persistence of
      LSDV from experimentally infected A. hebraeum nymphs and R. decoloratus females
      after exposure to cold temperatures of 5  degrees C at night and 20  degrees C
      during the day for 2 months was reported. This observation suggests possible over
      wintering of the virus in these tick species.

PMID- 23975564
TI  - Transovarial passage and transmission of LSDV by Amblyomma hebraeum,
      Rhipicephalus appendiculatus and Rhipicephalus decoloratus.
AB  - Lumpy skin disease (LSD), an acute, sub-acute or inapparent disease of cattle, is
      caused by lumpy skin disease virus (LSDV), a member of the genus Capripoxvirus in
      the family Poxviridae. LSD is characterised by high fever, formation of
      circumscribed skin lesions and ulcerative lesions on the mucous membranes of the
      mouth, respiratory and digestive tracts. It is an economically important disease
      due to the permanent damage to hides, the reduction in productivity and trade
      restrictions imposed on affected areas. Transmission has been associated with
      blood-feeding insects such as stable flies (Stomoxysis calcitrans) and mosquitoes
      (Aedes aegypti). Mechanical (intrastadial) and transstadial transmission by
      Amblyomma hebraeum and Rhipicephalus appendiculatus as well as transovarial
      transmission by R. decoloratus have been reported. In this study transovarial
      passage of LSDV to larvae and subsequent transmission to recipient animals were
      demonstrated. The finding of transovarial passage of LSDV in female ticks shows
      the potential for A. hebraeum, R. appendiculatus and R. decoloratus to be
      reservoir hosts for LSDV. 

PMID- 23975565
TI  - New tick records from the state of Rondonia, western Amazon, Brazil.
AB  - From 2005 to 2012, ticks were collected from different hosts at different
      localities of the state of Rondonia. The following 16 ixodid tick species were
      identified: Ixodes fuscipes, Amblyomma auricularium, Amblyomma coelebs, Amblyomma
      dubitatum, Amblyomma geayi, Amblyomma humerale, Amblyomma latepunctatum,
      Amblyomma longirostre, Amblyomma naponense, Amblyomma nodosum, Amblyomma
      oblongoguttatum, Amblyomma ovale, Amblyomma romitii, Amblyomma rotundatum,
      Amblyomma scalpturatum, and Amblyomma varium. From these, A. auricularium, A.
      dubitatum, and A. geayi are reported for the first time in the state of Rondonia.
      We provide the following tick-host associations that have not been reported
      anywhere: A. longirostre on Pteroglossus bitorquatus, A. rotundatum on
      Hydrodynastes gigas, and A. latepunctatum and A. scalpturatum on Hydrochoerus
      hydrochaeris. An adult male specimen of A. rotundatum is reported on Boa
      constrictor, comprising only the fourth male specimen to be recorded for this
      obligate parthenogenetic tick species. We also report the presence of the argasid
      species Ornithodoros kohlsi for the first time in Brazil, based on larval
      specimens collected on bats Molossops (Neoplatymops) mattogrossensis in Monte
      Negro, Rondonia. The present study increases the Brazilian tick fauna to 65
      species, from which 34 species (52 %) are now registered to Rondonia. Such high
      diversity of ticks in a relatively small state, associated with increasing
      environmental alteration due to deforestation and human occupation, makes
      Rondonia a potential source of tick-borne diseases.

PMID- 23975566
TI  - Double-lumen tube tracheal intubation using a rigid video-stylet: a randomized
      controlled comparison with the Macintosh laryngoscope.
AB  - BACKGROUND: Despite an increasing need, there is limited experience of double
      lumen endobronchial tube (DLT) placement using video laryngoscope. We evaluated
      DLT intubation using an OptiScope, a rigid video-stylet with a malleable tip
      derived from the Clarus Video System, in comparison with a Macintosh
      laryngoscope. METHODS: After airway evaluation and anaesthetic induction, Cormack
      and Lehane (C and L) grade was initially assessed in all patients using a
      Macintosh laryngoscope before tracheal intubation. The trachea was then intubated
      using either a Macintosh laryngoscope (n=200) or an OptiScope(r) (n=200). Success
      rate, intubation time, number of attempts at intubation, vocal cord view during
      intubation, need for external manipulation, and the incidences of oral mucosal or
      dental injury were compared between the two devices. RESULTS: Data were analysed
      for 397 patients. Intubation time with the OptiScope(r) was faster [median (inter
      quartile range): 15 (12-19) s] than with the Macintosh [18(12-28) s] {mean
      difference [95% confidence interval (CI)}: 5.5 (3.8-13.2) s, P=0.010]. The
      success rate of the first intubation was higher with the OptiScope(r) than with
      the Macintosh [80.4% vs 89.9%, odds ratio (95% CI): 2.2 (1.22-3.87), P=0.036].
      Initial view of the vocal cords was also better, although the final success rate
      was not different between devices. The need for external laryngeal manipulation,
      oral mucosal, or dental injury was lower with the OptiScope(r) compared with the
      Macintosh laryngoscope (all P<0.01). CONCLUSIONS: The OptiScope(r) provides
      faster tracheal intubation and a higher success rate for the first intubation
      with less trauma and a better vocal cord view than the Macintosh laryngoscope.

PMID- 23975567
TI  - Minimal alveolar concentration of sevoflurane for induction of isoelectric
      electroencephalogram in middle-aged adults.
AB  - BACKGROUND: We determined the minimal alveolar concentration (MAC) of sevoflurane
      inducing an isoelectric EEG in 50% of adult subjects (MACie). METHODS: We
      included 31 middle-aged subjects; 30 subjects finished the study protocol and
      received sevoflurane at preselected concentrations according to a modified Dixon
      'up-and-down' design starting at 1.7 vol% with 0.2 vol% steps size. General
      anaesthesia was induced and maintained with sevoflurane; tracheal intubation was
      facilitated with cisatracurium. After a period of 30 min before skin incision,
      the state of isoelectric EEG was considered as significant when a burst
      suppression ratio of 100% lasted for >1 min. The haemodynamic responses to skin
      incision and the vasopressor requirement to maintain stable haemodynamic status
      were also analysed according to the EEG state. RESULTS: MACie was 3.5% (95%
      confidence interval, 3.4-3.7%) in middle-aged subjects. When compared with
      subjects not in isoelectric EEG state, subjects in isoelectric EEG state received
      more phenylephrine to maintain stable haemodynamics (10 of 10 compared with 7 of
      20 subjects, P=0.001) and experienced less sympathetic responses to skin incision
      (1 of 10 compared with 11 of 20 subjects, P=0.024). CONCLUSIONS: MACie for
      sevoflurane was ~2.1 times MAC for immobilization in phenobarbital premedicated
      middle-aged adults. Sevoflurane-induced isoelectric EEG state is associated with
      significant cardiovascular depression but reduced haemodynamic responses to skin
      incision.

PMID- 23975568
TI  - Effects of LED phototherapy on relative wound contraction and reepithelialization
      during tissue repair in hypothyroid rats: morphometric and histological study.
AB  - The aim of this study was to assess morphometrically and histologically, the
      effects of light-emitting diode (LED) (lambda630 +/- 20 nm) phototherapy on
      reepithelialization and wound contraction during tissue repair in hypothyroid
      rats. Thyroid hormone deficiency has been associated with disorders of tissue
      repair. LED phototherapy has been studied using several healing models, but their
      usefulness in the improvement of hypothyroidism wound healing remains unknown.
      Under general anesthesia, a standard surgical wound (1 cm(2)) was produced on the
      dorsum of 48 male Wistar rats divided into four groups of 12 animals each: EC
      control euthyroid, ED-euthyroid + LED, HC-control hypothyroid, and HD-Hypothyroid
      + LED. The irradiation started immediately after surgery and was repeated every
      other day for 7 and 14 days. Photographs of the wound were taken at the day of
      the surgical procedure and on days 8 and 15 after surgery, when animals' deaths
      occurred. The specimens were removed, routinely processed, and stained with
      hematoxylin/eosin. Seven days after the surgery, it was possible to observe
      statistically significant reductions in the wound area of the irradiated
      euthyroid group, in comparison to hypothyroid group, irradiated and non
      irradiated (ANOVA, p < 0.05). The reepithelialization was significantly higher in
      the euthyroid and hypothyroid groups irradiated with LED than in the non
      irradiated groups (Fisher's test, p < 0.05). No significant difference was found
      in the experimental period of 14 days among the groups. The hypothyroidism
      delayed wound healing and the LED phototherapy, at these specific parameters,
      improved the process of reepithelialization in the presence of hypothyroidism. 

PMID- 23975569
TI  - Morphological alterations on Citrobacter freundii bacteria induced by erythrosine
      dye and laser light.
AB  - The effect of the laser irradiation (532 nm) on films prepared from Citrobacter
      freundii mixed with erythrosine dye was investigated by using atomic force
      microscopy. It was observed that morphological changes of bacterial surfaces
      after irradiations, which were attributed to cellular damage of the outer
      membranes, are a result of a photodynamic effect. The results suggested that the
      combination of erythrosine and laser light at 532 nm could be a candidate to a
      photodynamic therapy against C. freundii.

PMID- 23975570
TI  - Rapid-acquisition myocardial perfusion scintigraphy (MPS) on a novel gamma camera
      using multipinhole collimation and miniaturized cadmium-zinc-telluride (CZT)
      detectors: prognostic value and diagnostic accuracy in a 'real-world' nuclear
      cardiology service.
AB  - AIMS: To study the prognostic value of rapid-acquisition adenosine stress-rest
      myocardial perfusion scintigraphy (MPS) on a gamma camera using multipinhole
      collimation and cadmium-zinc-telluride (CZT) detectors. The secondary aim was to
      assess the diagnostic accuracy of the technique compared with invasive coronary
      angiography. METHODS AND RESULTS: Retrospective analysis of 1109 consecutive
      patients undergoing MPS in a routine clinical setting on a high-efficiency
      multipinhole gamma camera. MPS acquisition, performed with a standard injection
      of 550 MBq of (99m)Tc-tetrofosmin, required a mean (+/-SD) scanning time of 322
      +/- 51 s. The hard cardiac event rate at a median (inter-quartile range) follow
      up of 624 (552-699) days was 0.4% (95% CI 0.1-1.1) in patients with no
      significant perfusion abnormality versus 6.8% (95% CI 4.3-10.7%, P < 0.001) in
      those with an abnormal scan. In a sub-group of 165 patients, comparison with
      obstructive coronary artery disease on X-ray angiography gave a sensitivity,
      specificity, positive predictive value, negative predictive value, and accuracy
      for rapid-acquisition MPS of 84% (95% CI 74-91), 79% (95% CI 68-87), 82% (95% CI
      72-89), 81% (95% CI 70-89), and 82% (95% CI 73-89), respectively. CONCLUSIONS:
      MPS performed on a CZT solid-state detector camera with multipinhole collimation
      is an evolutionary development that provides reliable prognostic and diagnostic
      information, while significantly reducing image acquisition time.

PMID- 23975571
TI  - Factors affecting the stability and performance of ipratropium bromide; fenoterol
      hydrobromide pressurized-metered dose inhalers.
AB  - The aim of the study was to investigate the factors affecting the stability and
      performance of ipratropium bromide and fenoterol hydrobromide in a pressurized
      metered dose inhaler (pMDI). A factorial design was applied to investigate the
      effects of three parameters (propellant, water, and ethanol) on the performance
      of 27 designed formulations of a solution-based pMDI. The formulations that
      contained a hydrofluoroalkane (HFA) propellant lower than 72% v/v and an ethanol
      concentration higher than 27% v/v remained as clear solutions. Nine formulations
      that contained the HFA propellant higher than 74% v/v precipitated. The results
      indicated that it was not only the HFA propellant content of the formulations
      that was related to the formulation instability but also ethanol content. Only
      six formulations from the 18 formulations, that did not precipitate, produced
      drug contents that were within the acceptable range (80-120%). These six
      formulations generated aerosols with mass median aerodynamic diameters (MMAD) of
      approximately 2 MUm with a fine particle fraction (FPF; particle size, <6.4 MUm)
      between 45% and 52%. The MMAD and FPF did not change significantly after 6 months
      of storage (P > 0.05). 

PMID- 23975574
TI  - Unusually high levels of n-6 polyunsaturated fatty acids in whale sharks and reef
      manta rays.
AB  - Fatty acid (FA) signature analysis has been increasingly used to assess dietary
      preferences and trophodynamics in marine animals. We investigated FA signatures
      of connective tissue of the whale shark Rhincodon typus and muscle tissue of the
      reef manta ray Manta alfredi. We found high levels of n-6 polyunsaturated fatty
      acids (PUFA), dominated by arachidonic acid (20:4n-6; 12-17 % of total FA), and
      comparatively lower levels of the essential n-3 PUFA-eicosapentaenoic acid (20:5n
      3; ~1 %) and docosahexaenoic acid (22:6n-3; 3-10 %). Whale sharks and reef manta
      rays are regularly observed feeding on surface aggregations of coastal crustacean
      zooplankton during the day, which generally have FA profiles dominated by n-3
      PUFA. The high levels of n-6 PUFA in both giant elasmobranchs raise new questions
      about the origin of their main food source. 

PMID- 23975573
TI  - Rapid detection and quantification of triacylglycerol by HPLC-ELSD in
      Chlamydomonas reinhardtii and Chlorella strains.
AB  - Triacylglycerol (TAG) analysis and quantification are commonly performed by first
      obtaining a purified TAG fraction from a total neutral lipid extract using thin
      layer chromatography (TLC), and then analyzing the fatty acid composition of the
      purified TAG fraction by gas chromatography (GC). This process is time-consuming,
      labor intensive and is not suitable for analysis of small sample sizes or large
      numbers. A rapid and efficient method for monitoring oil accumulation in algae
      using high performance liquid chromatography for separation of all lipid classes
      combined with detection by evaporative light scattering (HPLC-ELSD) was developed
      and compared to the conventional TLC/GC method. TAG accumulation in two
      Chlamydomonas reinhardtii (21 gr and CC503) and three Chlorella strains (UTEX
      1230, CS01 and UTEX 2229) grown under conditions of nitrogen depletion was
      measured. The TAG levels were found to be 3-6 % DW (Chlamydomonas strains) and 7
      12 % DW (Chlorella strains) respectively by both HPLC-ELSD and TLC/GC methods.
      HPLC-ELSD resolved the major lipid classes such as carotenoids, TAG,
      diacylglycerol (DAG), free fatty acids, phospholipids, and galactolipids in a 15
      min run. Quantitation of TAG content was based on comparison to calibration
      curves of trihexadecanoin (16:0 TAG) and trioctadecadienoin (18:2 TAG) and showed
      linearity from 0.2 to 10 MUg. Algal TAG levels >0.5 MUg/g DW were detectable by
      this method. Furthermore TAG content in Chlorella kessleri UTEX 2229 could be
      detected. TAG as well as DAG and TAG content were estimated at 1.6 % DW by HPLC
      ELSD, while it was undetectable by TLC/GC method. 

PMID- 23975576
TI  - Psychological stress-induced lower serum zinc and zinc redistribution in rats.
AB  - In humans, long-term exposure to uncontrollable and unpredictable life stressors
      is a major precipitant in the development of depressive disorders. There are
      strong evidences that depression is accompanied by lower serum zinc. The aim of
      present study is to assess the effects of repeated psychological stress (PS) on
      the zinc metabolism in rat. The rats were divided into control group and PS group
      which were subdivided into three subgroups: 7-day group, 14-day group, and
      recovery group (ten rats in each subgroup). PS model was created by a
      communication box which contains room A and room B. Rats in room A were only
      exposed to the responses of rats which were randomly given electrical shock for
      30 min in room B. PS was given to rats for 30 min every morning for 14 days. The
      serum corticosterone (CORT), zinc in serum and tissues, and zinc apparent
      absorption after PS exposure were investigated. The results showed that the serum
      CORT increased and serum zinc decreased after 7 and 14 days of PS treatment. The
      zinc concentration in the liver was increased by 14 days PS exposure, whereas its
      concentration in the hippocampus was decreased by 7 and 14 days of PS exposure.
      There were no significant changes in zinc concentration in the heart, spleen,
      kidney, duodenum, cortex, and cerebellum. A decrease in the zinc apparent
      absorption was observed in the 7- and 14-day PS groups. The increased serum CORT
      and liver zinc concentrations and decreased serum zinc and apparent absorption of
      zinc recovered to normal concentrations 7 days away from PS exposure. The results
      suggest that PS could induce lower serum zinc, which might be correlated with
      decreased zinc absorption in the small intestine and increased liver zinc
      accumulation after PS exposure. The consequent effects of decreased hippocampal
      and serum zinc and increased CORT concentration after PS exposure on stress
      related diseases await further research.

PMID- 23975575
TI  - Dietary fat in relation to erythrocyte fatty acid composition in men.
AB  - Erythrocyte membrane fatty acid (EMFA) composition is used in the validation of
      food frequency questionnaires (FFQ) and the evaluation of dietary fat quality. In
      this cross-sectional study we aimed to investigate associations of diet with
      EMFA. Altogether, 1,033 randomly selected Finnish men, aged from 47 to 75 years
      filled in a FFQ and their EMFA composition was analyzed. Marine polyunsaturated
      fatty acid (PUFA) intake correlated positively with erythrocyte eicosapentaenoic
      and docosahexaenoic acids (r(s) = 0.415 and r(s) = 0.340, respectively, P <
      0.001) and inversely with all n-6 PUFA analyzed (P < 0.001). PUFA intake from
      spreads and cooking fats correlated positively with alpha-linolenic (ALA),
      linoleic (LNA) and nervonic acids (r(s) = 0.229, r(s) = 0.160 and r(s) = 0.143,
      respectively, P < 0.001). Milk fat intake was associated with myristic and
      behenic acids (r(s) = 0.186 and r(s) = 0.132, respectively P < 0.001). Butter
      users had lower ALA and LNA proportions (mol%) than non-users (0.16 +/- 0.04 vs.
      0.19 +/- 0.05, P < 0.001 and 7.77 +/- 1.02 vs. 8.12 +/- 1.11, P = 0.001). Higher
      PUFA intake from meat was related to decreased long-chain n-3 (P < 0.001) and
      increased n-6 PUFA (P < 0.001) proportions. In conclusion, EMFA composition
      reflects particularly well the intakes of n-3 PUFA, whereas other associations
      remained lower. Yet, all main sources of dietary fat were related with EMFA. The
      dietary effect on the nervonic acid proportion was confirmed.

PMID- 23975578
TI  - Differences in trace metal concentrations (Co, Cu, Fe, Mn, Zn, Cd, And Ni) in
      whole blood, plasma, and urine of obese and nonobese children.
AB  - High-performance ion chromatography and inductively coupled plasma-mass
      spectrometry methods have been applied to estimate the content of Cd, Co, Cu, Fe,
      Mn, Zn, and Ni in whole blood, plasma, and urine of obese and nonobese children.
      The study was conducted on a group of 81 Polish children of age 6-17 years (37
      males, 44 females). Obese children were defined as those with body mass index
      (BMI) >95th percentile in each age-gender-specific group. Statistical testing was
      done by the use of nonparametric tests (Kruskal-Wallis's and Mann-Whitney's U)
      and Spearman's correlation coefficient. Significant correlations appeared for
      control group in plasma (Mn-Cd, Ni-Co), urine (Cu-Co), and blood (Fe-Cu), while
      for obese patients in plasma (Cd-Mn, Ni-Cu, Ni-Zn) and urine (Fe-Cd, Co-Mn). Sex
      criteria did not influence correlations between metals' content in plasma and
      urine of obese patients. Metals' abundance was correlated in non-corresponding
      combinations of body fluids. Rare significant differences between content of
      metals according to sex and the type of body fluids were discovered: Zn in plasma
      from obese patients of both sexes, and Zn, Co, and Mn in blood, Mn in plasma from
      healthy subjects. Negative correlations between BMI and Zn in blood, Cu in
      plasma, and Fe in urine were discovered for girls (control group). Positive
      correlation between Co content in plasma and BMI was discovered for obese boys.
      The changes in metals' content in body fluids may be indicators of obesity.
      Content of zinc, copper, and cobalt should be monitored in children with elevated
      BMI to avoid deficiency problems.

PMID- 23975579
TI  - Effect of anatase nanoparticles (TiO2) on parsley seed germination (Petroselinum
      crispum) in vitro.
AB  - Nano priming is a new method for the increase of seedling vigor and improvement
      of germination percentage and seedling growth. The experiments to evaluate the
      effect of different concentrations of nano-anatase on germination parameters of
      parsley as a completely randomized design with five replications were performed
      in a tissue culture laboratory of the Department of Horticulture, Shahid Chamran
      University of Ahvaz. In addition, nano-anatase at four concentrations (10, 20,
      30, and 40 mg/ml) was added to the Murashige and Skoog medium. At the end of the
      experiment, the percentage of germination, germination rate index, root and shoot
      length, fresh weight of seedlings, vigor index, and chlorophyll content were
      evaluated. The results showed that an increase in the concentration of nano
      anatase caused a significant increase in the percentage of germination,
      germination rate index, root and shoot length, fresh weight, vigor index, and
      chlorophyll content of seedlings. The best concentration of nano-anatase was 30
      mg/ml.

PMID- 23975581
TI  - Effect of dietary yeast chromium and L-carnitine on lipid metabolism of sheep.
AB  - A 56-day feeding experiment was conducted to investigate the effects of yeast
      chromium (Cr, 300 MUg/kg diet) and/or L-carnitine (100 mg/kg diet) on lipid
      metabolism and their interaction in sheep. After a 14-day adaptation period, 32 3
      month-old sheep were randomly divided into four groups of eight. All sheep were
      fed with basal diets according to the American feeding standard of the National
      Research Council. At the end of the experiment, yeast Cr and/or L-carnitine
      supplementation significantly decreased abdominal fat mass and abdominal fat
      percentage, suggesting an improved mutton quality. Compared with the control
      group, the ratio of glucose to insulin was significantly increased, due to
      unchanged glucose levels and reduced insulin levels in yeast Cr and/or L
      carnitine supplement groups, indicating high insulin sensitivity and well
      controlled serum glucose levels. In addition, yeast chromium and/or L-carnitine
      induced significant decreases in serum triglyceride levels and serum total
      cholesterol levels, while increasing serum free fatty acid levels and high
      density lipoproteincholesterol levels. The findings show that adding a yeast Cr
      and/or L-carnitine supplement may give better control of glucose and lipid
      variables.

PMID- 23975580
TI  - Ecological risks assessment and pollution source identification of trace elements
      in contaminated sediments from the Pearl River Delta, China.
AB  - Sediments from 14 stations in the Foshan Waterway, a river crossing the
      industrial district of Guangdong Province, South China, were sampled and
      subsequently analyzed. The 14 stations were selected for the pollution
      discharging features of the river, such as the hydrology, the distribution of
      pollution sources, and the locations of wastewater outlets. The ecological risks
      were assessed, and the pollution sources were identified to provide valuable
      information for environmental impact assessment and pollution control. The
      spatial variability was high and the range were (in milligrams per kilogram dry
      weight): Pb, 46.0~382.8; Cu, 33.7~ 482.3; Zn, 62.2~1,568.7; Ni, 28.5~130.7; Cr,
      34.7~1,656.1; Cd, 0.50~8.53; Hg, 0.02~8.27; and As, 5.77~66.09. The evaluation
      results of enrichment factor and potential ecological risk index indicate that
      the metal pollution in the surface and bottom sediments were severely polluted
      and could pose serious threat to the ecosystem in most stations. Although the
      hazard levels of the trace element differed among the stations, Hg was the most
      serious pollutant in all stations. The results of principal component analysis
      (PCA) show that the discharge of industrial wastewater is the most important
      polluting factor whereas domestic sewage, which contains a large amount of
      organic substances, accelerates metal deposition. And potential pollution sources
      were identified by the way of integrating the analysis results of PCA and data
      gained from the local government. Therefore, the conclusion is drawn that Foshan
      Waterway is seriously polluted with trace elements, both in the surface sediment
      (0 to 20 cm) and the bottom sediments (21 to 50 cm) are contaminated.

PMID- 23975582
TI  - Trace element concentration in hair samples as an indicator of exposure of
      population in the Negev, Israel.
AB  - The concentration of the toxic elements Ag, As, Cd, Co, Mn, Mo, Pb, Se, and U and
      the elements Al, Mg, Cu, Fe, and Zn in human hair samples of population living in
      the north of the Negev Desert in Israel was determined. The study population
      consisted of three subgroups: Jewish urban population, Bedouin urban population,
      and Bedouins living in unrecognized villages (the "dispersion"). The main focus
      is on the differences between these subgroups in an attempt to explore factors
      responsible for the variation in trace metal contents in hair samples. The
      results show that the level of several elements, particularly Ag, Mn, and Pb, in
      the female Bedouin group significantly differed from the other groups in the
      study. Exploring the reasons for these differences, we concluded that the
      lifestyle of those women is the main cause. The female Bedouin subgroup is
      exposed to heavy metals from kitchen utensils, jewelry, and makeup. Therefore,
      differences in the heavy metal concentration in the hair samples of this group
      were attributed to the traditional unique lifestyle and social behavior of the
      females in the Bedouin society. 

PMID- 23975583
TI  - Atypical osteoid osteomas.
AB  - Osteoid osteoma is a very painful benign bone tumor that affects young adults. It
      is exceptional before 5 and after 30 years of age. It can be seen in any part of
      the skeleton. Presentation of the tumor may be intracortical, juxta-cortical or
      cancellous. In long bones, the tumor is frequently intracortical, and in the
      spine, it is usually located at the posterior elements. Osteoid osteomas having
      radiologic and clinical features other than classical presentation of osteoid
      osteoma are called atypical osteoid osteomas. Atypical osteoid osteomas are
      important because the diagnosis and treatment are often complicated in these
      cases. Misdiagnosis with prolonged impairment and sometimes overtreatment appears
      as a major problem concerning atypical osteoid osteomas. This paper gives brief
      general information about the classical presentation of osteoid osteoma,
      discusses the pathogenesis of the lesion and focuses on the clinical
      presentation, radiologic features and characteristics of atypical osteoid
      osteomas as well as their treatment modalities.

PMID- 23975585
TI  - Feline focus: Diagnostic testing for feline thyroid disease: hyperthyroidism.
AB  - In older cats presenting with clinical features of hyperthyroidism, confirming
      the diagnosis of thyroid disease is usually straightforward. However, the
      potential for false-negative and false-positive results exists with all thyroid
      function tests, especially when used for routine screening of large numbers of
      asymptomatic cats. Therefore, all thyroid function test results must be
      interpreted in light of the cat's history, clinical signs, and other laboratory
      findings. If a high serum thyroxine (T4) value is found in a cat that lacks
      clinical signs of hyperthyroidism, or if hyperthyroidism is suspected in a cat
      with normal total T4 concentrations, repeating the total T4 analysis, determining
      the free T4 concentration, or performing thyroid scintigraphy may be needed to
      confirm the diagnosis. 

PMID- 23975584
TI  - The current spectrum of infection in cancer patients with chemotherapy related
      neutropenia.
AB  - Despite advancements in the treatment and supportive care of patients with
      malignant disorders, neutropenia remains the major side effect of most
      antineoplastic regimens. Infections occur frequently in neutropenic patients and
      are associated with considerable morbidity and mortality. The spectrum of
      infection continues to change, and is influenced by various factors including
      local epidemiology, the use of chemoprophylaxis, and the use of central venous
      catheters and other medical devices. Bacterial infections are common in the early
      stages of neutropenia, with fungal infections emerging if neutropenia persists
      beyond 7-10 days. Gram-positive organisms cause most bacteremic infections
      (although this trend appears to be changing), whereas infections at other sites
      are often caused by Gram-negative bacilli or are polymicrobial, especially if
      deep tissue infection is present. Candida spp., and Aspergillus spp., remain the
      most common fungal pathogens, although several opportunistic fungi have emerged.
      Resistance to antimicrobial and antifungal agents commonly used for the
      prevention and treatment of infections in neutropenic patients has become a
      significant problem. The prompt administration of appropriate, empiric,
      antimicrobial therapy, prior to the availability of microbiological culture
      results, is the standard of care. Up to date knowledge of the spectrum of
      infection and local susceptibility/resistance patterns, is critical. In this
      report, we describe the current spectrum of infection in patients with
      malignancies and neutropenia, and emphasize the fact that local and geographic
      differences are not infrequent. We recommend that individual institutions conduct
      periodic epidemiological surveys in order to have the latest data available for
      the optimal management of their patients.

PMID- 23975586
TI  - Feline focus: Diagnostic testing for feline thyroid disease: hypothyroidism.
AB  - Although naturally occurring hypothyroidism is very rare in cats, iatrogenic
      hypothyroidism is a recognized complication of treatment for hyperthyroidism.
      However, confirming the diagnosis of hypothyroidism in cats is not generally
      straightforward. The potential for false-negative and false-positive results
      exists with all thyroid function tests, especially in older cats that may have
      concurrent nonthyroidal illness. Therefore, all thyroid function test results
      must be interpreted in light of the cat's history, clinical signs, and other
      laboratory findings. If a low to low-normal serum thyroxine (T4) value is found
      in a cat that has been treated for hyperthyroidism, repeating the total T4
      analysis, determining free T4 and thyroid stimulating hormone (TSH)
      concentrations, or performing a TSH stimulation test or thyroid scintigraphy may
      be needed to confirm the diagnosis. 

PMID- 23975587
TI  - Laparoscopic trans-peritoneal hernioplasty (TAPP) is useful for obturator
      hernias: report of a case.
AB  - A 71-year-old female presented to our hospital due to pain from the right hip
      joint to the lower abdomen. The pain had suddenly appeared and spontaneously
      disappeared more than 10 times during the past 2 years. She had visited many
      hospitals, but remained undiagnosed. The patient underwent a computed tomography
      (CT) scan of the pelvis, and a soft tissue shadow was seen between the external
      obturator and pectineal muscles. She was diagnosed with a right obturator hernia
      and underwent elective repair by laparoscopic trans-peritoneal hernioplasty
      (TAPP). 1 year has passed since the surgery, without any recurrence of the
      abdominal pain. Obturator hernias are rare, and most cases are found as
      incarcerated hernias. It is rare to find an obturator hernia without intestinal
      obstruction, or with the recurrent pain as in our case. We herein report a case
      in which an obturator hernia was undiagnosed and intermittent pain was
      experienced for 2 years prior to TAPP, which appears to have successfully treated
      the hernia.

PMID- 23975588
TI  - DNA index is a strong predictive marker in intrahepatic cholangiocarcinoma: the
      results of a five-year prospective study.
AB  - PURPOSE: Predictive markers for risk stratification among patients with
      intrahepatic cholangiocarcinoma (IHC) are still lacking. Therefore, recent
      studies have focused on identifying the biological aspects of tumors that can
      provide more information about the tumor aggressiveness. The aim of this study
      was to prospectively evaluate the prognostic potential of the DNA index in
      patients undergoing liver resection for IHC. METHODS: In a prospective long-term
      follow-up study, the DNA index of 65 IHC patients undergoing liver resection was
      assessed by DNA image cytometry, and this parameter, as well as standard
      histopathological parameters, correlated with the patient survival. RESULTS: The
      mean DNA index was 1.69 +/- 0.66 (range, 0.9-4.3). The univariate survival
      analysis showed that the DNA index (p = 0.024) and tumor stage (p = 0.017) were
      associated with patient survival, whereas all other standard histopathological
      factors had no predictive value. The multivariate analysis identified the DNA
      index (p = 0.050) and tumor stage (p = 0.028) as independent prognostic
      parameters. CONCLUSIONS: The DNA index is an independent predictive marker for
      IHC after liver resection. It is superior to most standard histopathological
      parameters and can be assessed pre- and postoperatively. Therefore, the DNA index
      might represent a promising tool in the decision-making process for patients with
      IHC.

PMID- 23975589
TI  - Usefulness of serum p53 antibody measurement in colorectal cancer: an examination
      of 1384 primary colorectal cancer patients.
AB  - PURPOSES: Recently, the serum p53 antibody (S-p53Ab) has been used widely in
      clinical practice as a tumor marker for colorectal cancer (CRC). However, no
      large-scale studies have examined the usefulness of serial measurements of S
      p53Ab or have established the relationship of this parameter with the
      clinicopathological factors of CRC. METHODS: An ELISA for S-p53Ab was performed
      for 1384 primary CRC patients, and the results were categorized by the
      clinicopathological factors. RESULTS: The S-p53Ab positivity rate was 24.1 %, and
      was significantly higher in Stage III-IV than in Stage 0-II cases. However, no
      relationship was seen with the serum carcinoembryonic antigen (CEA) or
      carbohydrate antigen 19-9 (CA19-9) levels. The addition of the S-p53Ab assay to
      the CEA and CA19-9 measurements increased the overall diagnostic sensitivity to
      50.9 % (CEA and/or CA19-9: 37.3 %). In patients who had undergone complete
      resection, S-p53Ab positivity was associated with a decrease in the relapse-free
      survival (p = 0.012), but it was not independent prognostic indicator. S-p53Ab
      positivity had no influence on the cancer-specific survival. CONCLUSIONS: The S
      p53Ab positivity rate was higher than the positivity rates for CEA and/or CA19-9
      in Stage 0-I CRC patients. Combining the use of the three tumor marker tests is a
      potentially effective method for detecting even early-stage CRC.

PMID- 23975590
TI  - Laparoscopic antireflux surgery improves esophageal body motility in patients
      with severe reflux esophagitis.
AB  - PURPOSE: This study was designed to clarify whether laparoscopic antireflux
      surgery (LARS) improves the esophageal body motility (EBM) in patients with
      reflux esophagitis. METHODS: Thirty-five patients with gastroesophageal reflux
      disease (GERD) scheduled to undergo LARS were divided into a mild esophagitis
      group (ME; n = 18, Grade O:A:B = 7:10:1) and a severe esophagitis group (SE; n =
      17, Grade C:D = 13:4), according to the Los Angeles classification of reflux
      esophagitis. The types of fundoplication (Nissen/Toupet) were 6/12 in the ME
      group and 4/13 in the SE group. Esophageal pH monitoring and manometry were
      performed before and 1 year after surgery. RESULTS: The fraction time of a pH
      below 4 significantly decreased after surgery in both groups. The LES pressures
      did not change significantly after surgery in the ME group, but significantly
      increased in the SE group. The peristaltic amplitudes 18 and 13 cm above the LES
      did not change significantly after surgery in either group. The peristaltic
      amplitudes 8 and 3 cm above the LES did not change significantly after surgery in
      the ME group, but significantly increased after surgery in the SE group.
      CONCLUSIONS: The preoperative EBM was not improved by LARS in patients with GERD
      and mild mucosal breaks in the esophagus, but the preoperative middle to distal
      EBM was improved by LARS in patients with GERD and severe mucosal breaks.

PMID- 23975591
TI  - Pancreatic cancer in the remnant pancreas following primary pancreatic resection.
AB  - PURPOSE: To clarify the clinical features of cancer in the pancreatic remnant.
      METHODS: We retrospectively reviewed the clinical and pathological findings of 10
      patients who developed remnant pancreatic cancer in our hospital between 2002 and
      2012. The KRAS sequences in both the initial pancreatic tumor and remnant
      pancreatic cancer were examined in two patients. RESULTS: Eight patients
      underwent a second pancreatectomy for remnant pancreatic cancer (resected group),
      while two patients were not operated on and underwent chemotherapy (unresected
      group). The remnant pancreatic cancer developed at the cut end of the pancreas
      (pancreaticogastrostomy site) in four patients. In the resected group, four
      patients died 17 months after the emergence of the remnant pancreatic cancer and
      four patients survived during the median 40.5-month observation period. The
      median survival of the unresected group after the emergence of the remnant
      pancreatic cancer was 10 months. The findings of the KRAS sequencing and
      immunohistological staining of the remnant pancreatic cancer for MUC1 and MUC2 in
      the two patients were consistent with those of the initial pancreatic tumor in
      one patient, and not consistent in the other. CONCLUSIONS: Our results suggest
      that both local recurrence and a new primary cancer can develop in the pancreatic
      remnant, and repeated pancreatectomy can prolong survival.

PMID- 23975593
TI  - Assessment of the impact on time to complete medical record using an electronic
      medical record versus a paper record on emergency department patients: a study.
AB  - BACKGROUND: Electronic medical records are becoming an integral part of
      healthcare delivery. OBJECTIVE: The goal of this study was to compare paper
      documentation versus electronic medical record for non-traumatic chest pain to
      determine differences in time for physicians to complete medical records using
      paper versus electronic mediums. We also assessed physician satisfaction with the
      electronic format. METHODS: We conducted this before-after study in a single
      large tertiary care academic emergency department. In the 'Before Period',
      stopwatches determined the time for paper medical recording. In the 'After
      Period', a template-based electronic medical record was introduced and the time
      for electronic recording was measured. The time to record in the before and after
      periods were compared using a two-sided t test. We surveyed physicians to assess
      satisfaction. RESULTS: We enrolled 100 non-traumatic patients with chest pain in
      the before period and 73 in the after period. The documentation time was longer
      using electronic charting, (9.6+/-5.9 min vs 6.1+/-2.5 min; p<0.001). 18 of 20
      physicians participating in the after period completed surveys. Physicians were
      not satisfied with the electronic patient recording for non-traumatic chest pain.
      CONCLUSIONS: This is the first study that we are aware of which compared paper
      versus electronic medical records in the emergency department. Electronic
      recording took longer than paper records. Physicians were not satisfied using
      this electronic record. Given the time pressures on emergency physicians, a
      solution to minimise the charting time using electronic medical records must be
      found before widespread uptake of electronic charting will be possible.

PMID- 23975592
TI  - Detection of intrahepatic veno-venous shunts by three-dimensional venography
      using multidetector-row computed tomography during angiography.
AB  - PURPOSE: The hepatic vein (HV) can be removed during hepatectomy if there is an
      effective intrahepatic veno-venous shunt (vv-shunt). We evaluated the efficacy of
      vv-shunt detection by three-dimensional (3D) venography reconstructed from
      multidetector-row computed tomography (MDCT) during angiography. METHODS: 3D
      venography was reconstructed using computer software in 88 patients with
      intrahepatic tumors. RESULTS: We found that 12 patients had one shunt [4 right
      hepatic vein (RHV)-middle hepatic vein (MHV) and 12 RHV- inferior right hepatic
      vein (IRHV)] and 1 patient had 2 shunts (RHV-MHV and -IRHV), confirming a
      clinically efficient vv-shunt in 14.8% of the patients. In one patient with an
      RHV-IRHV shunt, the preserved RHV-IRHV shunt worked well and prevented congestion
      of the postero-caudal subsegment after central bisegmentectomy with partial
      resection of the RHV ventral trunk for huge hepatocellular carcinoma (HCC).
      CONCLUSIONS: Although the vv-shunt detection rate by 3D venography is low, a
      visualized vv-shunt proved to be efficient. Thus, invasive occlusion venography
      is avoidable if a vv-shunt is seen on 3D venography.

PMID- 23975594
TI  - The current status and future perspectives of clinical trial groups in Japan.

PMID- 23975595
TI  - Synthesis of chromeno[3,4-B]quinoline derivatives by heterogeneous
      [Cu(II)BHPPDAH] catalyst without being immobilized on any support under mild
      conditions using PEG 300 as green solvent.
AB  - The efficient synthesis of chromeno[3,4-[Formula: see text]]quinoline derivatives
      by condensation of O-propargylated salicylaldehyde, or corresponding compounds
      and primary aromatic amine derivatives using a catalytic amount of heterogeneous
      Cu(II)BHPPDAH complex without being immobilized on any supports (5.0 mol%) in PEG
      300 as a "green" solvent is described. The remarkable features of this protocol
      are good to high yields in all cases, short reaction times, a cleaner reaction
      profile in an environmentally benign solvent (PEG 300), and the method is
      applicable to large-scale operation without any problem. Furthermore, the
      catalyst was quantitatively recovered from the reaction mixture by simple
      filtration and reused at least seven times with almost consistent activity. 

PMID- 23975596
TI  - Parallel synthesis of 7-heteroaryl-pyrazolo[1,5-a]pyrimidine-3-carboxamides.
AB  - A simple and practical four-step protocol for the parallel synthesis of 7
      heteroaryl-pyrazolo[1,5-[Formula: see text]]pyrimidine-3-carboxamides was
      developed. The synthesis starts with transformation of commercially available 2
      acetylpyridine and acetylpyrazine with [Formula: see text] [Formula: see text]
      dimethylformamide dimethylacetal into the corresponding [Formula: see text]-3
      (dimethylamino)-1-(heteroaryl)prop-2-en-1-ones followed by cyclisation with
      methyl 5-amino-1[Formula: see text]-pyrazole-4-carboxylate to give methyl 7
      heteroarylpyrazolo[1,5-[Formula: see text]]pyrimidine-3-carboxylates. Hydrolysis
      of the ester group and subsequent amidation of the so formed carboxylic acids
      with 12 primary and secondary aliphatic amines furnished a library of 24 title
      compounds in good overall yields and purity. 

PMID- 23975597
TI  - Angiogenesis and vascular remodeling in chronic airway diseases.
AB  - Asthma and chronic obstructive pulmonary disease remain a global health problem,
      with increasing morbidity and mortality. Despite differences in the causal
      agents, both diseases exhibit various degrees of inflammatory changes, structural
      alterations of the airways leading to airflow limitation. The existence of
      transient disease phenotypes which overlap both diseases and which progressively
      decline the lung function has complicated the search for an effective therapy.
      Important characteristics of chronic airway diseases include airway and vascular
      remodeling, of which the molecular mechanisms are complex and poorly understood.
      Recently, we and others have shown that airway smooth muscle (ASM) cells are not
      only structural and contractile components of airways, rather they bear
      capabilities of producing large number of pro-inflammatory and mitogenic factors.
      Increase in size and number of blood vessels both inside and outside the smooth
      muscle layer as well as hyperemia of bronchial vasculature are contributing
      factors in airway wall remodeling in patients with chronic airway diseases,
      proposing for the ongoing mechanisms like angiogenesis and vascular dilatation.
      We believe that vascular changes directly add to the airway narrowing and hyper
      responsiveness by exudation and transudation of proinflammatory mediators,
      cytokines and growth factors; facilitating trafficking of inflammatory cells;
      causing oedema of the airway wall and promoting ASM accumulation. One of the key
      regulators of angiogenesis, vascular endothelial growth factor in concerted
      action with other endothelial mitogens play pivotal role in regulating bronchial
      angiogenesis. In this review article we address recent advances in pulmonary
      angiogenesis and remodelling that contribute in the pathogenesis of chronic
      airway diseases. 

PMID- 23975598
TI  - Sphingosine kinase-1 activation causes acquired resistance against Sunitinib in
      renal cell carcinoma cells.
AB  - Multi-target tyrosine kinase inhibitor Sunitinib has been widely used in cancer
      treatment, including metastatic renal cell carcinoma. However, most patients who
      initially benefit from Sunitinib develop resistance with extended usage of
      Sunitinib, which is referred to as "acquired resistance". The molecular
      mechanisms contributing to this acquired resistance remain poorly understood. In
      this present study, we established Sunitinib-resistant cell lines from human
      renal cell lines (786-O, A498, ACHN and CAKI1) by continuous treatment with
      Sunitinib to explore the molecular mechanism leading to Sunitinib resistance. We
      found that PDGFR-beta expression in cell seems to be a protective factor against
      Sunitinib resistance formation. In addition, we found that both SK1 and ERK were
      activated in Sunitinib-resistance cell lines and SK1 and ERK inhibitors could
      resensitize Sunitinib-resistant cell lines. In conclusion, our observations
      suggest that SK1 and ERK activation is a feature of resistant cell lines, which
      serves as an alternative pathway evading anti-tumor activity of Sunitinib. 

PMID- 23975599
TI  - Icariin synergizes with arsenic trioxide to suppress human hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is an aggressive malignancy with high
      chemoresistance to chemotherapeutics. Arsenic trioxide (ATO) is of therapeutic
      potential for the treatment of HCC; however, the therapeutic benefit of ATO is
      very limited due to narrow therapeutic window. Icariin is a natural compound
      which inhibits tumour cell growth and induces apoptotic cell death in a variety
      of cancer cells. This study was designed to determine whether Icariin can
      potentiate the antitumour activity of ATO in HCC treatment. Cell proliferation
      and apoptosis were measured using an MTT assay and flow cytometry respectively.
      Changes in reactive oxygen species (ROS) level and mitochondrial membrane
      potential were analysed by fluorescence signals. Protein expression was measured
      by western blotting and NF-kappaB activity was determined by ELISA assay. In
      addition, the antitumour effect of combination treatment with Icariin and ATO on
      HCC was evaluated using a murine HCC cancer xenograft model. Icariin inhibited
      proliferation and induced apoptosis in both of the tested HCC cell lines in a
      dose-dependent fashion. Icariin enhanced the antitumour activity of ATO both in
      vitro and in vivo. The antitumour activity of Icariin and its enhancement of the
      antitumour activity of ATO correlated with the generation of intracellular ROS
      and inhibition of NF-kappaB activity. Our results showed that Icariin potentiated
      the antitumour activity of ATO in HCC. Therefore, we propose that the combination
      treatment with Icariin and ATO might facilitate the optimization of ATO therapy
      for patients with HCC. 

PMID- 23975600
TI  - Editorial comments on patch size and mechanics in the surgery for post-infarction
      ventricular septal perforation.
AB  - Finite element analysis method (FEM) provides suitable methodology to analyze a
      target with complex shape such as VSP patch. In this study, by employing the FEM,
      Ito and colleagues showed the importance of using a large patch to eliminate the
      dead space between the patch and LV endocardium. Intuitionally many surgeons
      believed the same way, but it now has been proven mathematically. Although the
      FEM model has some limitation in part due to too much simplified model, I believe
      that the study provides useful information to the patch mechanics for VSP closure
      and that it will help improving the outcome of surgical treatment of VSP. 

PMID- 23975601
TI  - The coronary calcium treadmill test: a new approach to the initial workup of
      patients with suspected coronary artery disease.
AB  - Due to the growth of cardiac testing and increasing cost of cardiovascular
      healthcare, the development of more cost-effective strategies has now become a
      dominant issue regarding future utilization of cardiac imaging procedures. To
      that end, we review the potential of combining two relatively inexpensive tests,
      the coronary artery calcium (CAC) scan and exercise electrocardiography (ECG), as
      a first-line test for the workup of patients with suspected coronary artery
      disease (CAD). The CAC scan was initially introduced as a screening test for CAD,
      based on data indicating that it is a specific marker for atherosclerosis,
      predicts clinical risk in accordance with the magnitude of CAC, and provides
      incremental information for prognostic risk compared to more readily available
      clinical data. However, CAC scores also predict the likelihood of observing
      myocardial ischemia among patients undergoing exercise myocardial perfusion SPECT
      imaging. Exercise ECG predicts clinical events according to the ST-segment
      response and according to functional exercise capacity, with the latter parameter
      as a stronger predictor of clinical outcomes. Like CAC scores, exercise
      functional capacity can also be used to predict the likelihood of ischemia since
      ischemia diminishes proportionally with increasing exercise capacity. Recent work
      indicates that when patients are designated by Bayesian analyses into low,
      intermediate, and high likelihood categories for CAD based on clinical data and
      the response to exercise ECG, the frequency of inducible myocardial ischemia is
      very low among both low and intermediate CAD likelihood patients who have a CAC
      score <400. Future studies are needed to investigate what clinical factors might
      further modify the CAC-ischemia relationship. On the basis of current data, an
      initial testing strategy that employs the combined calcium treadmill test has the
      inherent ability to designate a substantial number of intermediate likelihood
      patients who would not require further testing due to relatively low CAC scores
      and reasonable functional capacity. 

PMID- 23975602
TI  - Long-term outcomes following a normal stress myocardial perfusion scan.

PMID- 23975603
TI  - Assessment of tissue perfusion changes in port wine stains after vascular
      targeted photodynamic therapy: a short-term follow-up study.
AB  - The occlusion effect of vascular targeted photodynamic therapy (V-PDT) for
      malformed vessels in port wine stains (PWS) often last for some time after the
      treatment. A relatively longer period after V-PDT is needed to accurately assess
      the final response of PWS microcirculation to the treatment. In this study, we
      intended to use laser speckle imaging (LSI) to assess the tissue perfusion
      changes of PWS at follow-up after V-PDT and preliminarily analyze the
      relationship between perfusion change and color bleaching. Seventeen patients
      with 40 PWS lesions were scanned by LSI before and 3-6 months after they received
      V-PDT. The speckle flow indices of PWS lesions and normal skin before and at
      follow-up after V-PDT were recorded. We also performed analyses on the
      correlation between perfusion changes and color bleaching. Before V-PDT, the 40
      PWS lesions showed higher perfusion than the normal skin (1,421 +/- 463 and 1,115
      +/- 386 perfusion unit (PU), respectively, P < 0.01). The PWS lesions scanned at
      follow-up showed decreased perfusion level compared to the preoperative values
      (1,282 +/- 460 and 1,421 +/- 463 PU, respectively, P < 0.01). After V-PDT, the
      perfusion change rates coincide well with the color bleaching rates (correlation
      coefficient, 0.73). In conclusion, the LSI system is capable of imaging PWS
      perfusion precisely, and it has shown promising results in assessing the changes
      of tissue perfusion of V-PDT for PWS, with objective and quantitative data, real
      time images, and a shorter detection time. It may also provide an effectiveness
      assessment method for the treatment of PWS. 

PMID- 23975605
TI  - Adults with ADHD: use and misuse of stimulant medication as reported by patients
      and their primary care physicians.
AB  - This study investigated the agreement on treatment for attention
      deficit/hyperactivity disorder (ADHD) between adults with ADHD and the primary
      care physicians responsible for their treatment. Adults with ADHD and the primary
      care physicians responsible for their ADHD treatment completed a survey. The
      kappa-statistic assessed physician-patient agreement on ADHD treatment variables.
      The eligible sample consisted of 274 patients with confirmed current or previous
      psychopharmacological treatment for ADHD and the physicians responsible for their
      treatment. We received 159 questionnaires (58.0 %) with sufficient information
      from both sources. There were no significant differences between participants and
      nonparticipants (N = 115) on ADHD sample characteristics. Participants' mean age
      was 37.6 years, and 75 (47.2 %) were females. There was high agreement for
      current pharmacological treatment for ADHD, current and last ADHD drug
      prescription, treatment for substance use, and misuse of stimulant medication.
      Agreement for nonpharmacological treatment for ADHD and treatment termination
      because of the side effects was low. A minority of participants from both sources
      reported misuse of stimulant medication. There was a moderate correlation between
      the physicians' clinical judgment and patients' self-report on current
      functioning. The study showed that primary care physicians and their patients
      agreed on the pharmacological but not the nonpharmacological, treatments given.
      They also agreed on patients' current functioning. Physicians and patients
      reported low levels of misuse of stimulant medication. The results show that
      pharmacological treatment for adults with ADHD can be safely undertaken by
      primary care physicians.

PMID- 23975604
TI  - Seeing stem cells at work in vivo.
AB  - Stem cell based-therapies are novel therapeutic strategies that hold key for
      developing new treatments for diseases conditions with very few or no cures.
      Although there has been an increase in the number of clinical trials involving
      stem cell-based therapies in the last few years, the long-term risks and benefits
      of these therapies are still unknown. Detailed in vivo studies are needed to
      monitor the fate of transplanted cells, including their distribution,
      differentiation, and longevity over time. Advancements in non-invasive cellular
      imaging techniques to track engrafted cells in real-time present a powerful tool
      for determining the efficacy of stem cell-based therapies. In this review, we
      describe the latest approaches to stem cell labeling and tracking using different
      imaging modalities. 

PMID- 23975607
TI  - Metabolic syndrome associated with hyperprolactinemia: a new indication for
      dopamine agonist treatment?

PMID- 23975608
TI  - [Emotions and welfare wane quickly in the face of death].

PMID- 23975610
TI  - Validity of self-reported genetic counseling and genetic testing use among breast
      cancer survivors.
AB  - INTRODUCTION: Despite the value of genetic counseling (GC) and genetic testing
      (GT) for high-risk breast cancer survivors, little is known about their uptake
      and validity of self-report data. This study evaluated the accuracy of self
      reported genetic counseling and testing rates among breast cancer survivors.
      METHODS: The current analysis focused on Stage 0-III female breast cancer
      survivors who were identified from an academic medical center's cancer registry
      and responded to a mailed survey (N = 452). Self-reported rates of GC and GT were
      validated using information from the electronic medical record. RESULTS: Overall,
      30.8 % of survivors reported having seen a genetic counselor in the time period
      after their breast cancer diagnosis and 33.6 % noted having a genetic test.
      Concordance and specificity were good for both genetic questions; concordance
      agreements ranged from 86-88 %, while specificity was 83-86 %. Sensitivity (97-98
      %) and negative predictive values (99 %) were excellent, while the positive
      predictive values for both GC and GT were poor (59-63 %). CONCLUSIONS: Among
      breast cancer survivors, self-reports of GC and GT were generally accurate,
      although a subset of respondents overestimated genetic service utilization.
      Future work should focus on validating GC and GT self-reports in medically
      underserved populations. IMPLICATIONS FOR CANCER SURVIVORS: Genetic counseling
      and testing are valuable aspects of survivorship care for high-risk breast cancer
      survivors; accurate understanding of their use is important for survivors,
      clinicians, and researchers.

PMID- 23975611
TI  - Perception of body odor-an overlooked consequence of long-term gastrointestinal
      and urinary symptoms after radiation therapy for prostate cancer.
AB  - PURPOSE: This study was conducted to investigate the association of long-term
      gastrointestinal and urinary symptoms with perceived fecal or urine body odor
      after radiation therapy for prostate cancer and its effect on survivors' quality
      of life. METHODS: We used a study-specific questionnaire to measure the
      occurrence of long-term gastrointestinal and urinary symptoms, the perception of
      fecal or urine body odor, and quality of life (QoL) 2 to 14 years after radiation
      therapy for prostate cancer. The questionnaire was sent to 895 eligible survivors
      who assessed symptom occurrence and QoL in the previous 6 months. RESULTS: We
      received a filled-in questionnaire from 874 (89 %) men. For the long-term
      gastrointestinal symptoms, 11/13 were associated with the perception of fecal
      body odor. For the long-term urinary symptoms, 11/11 were associated with the
      perception of urine body odor. Men who perceived fecal or urine body odor had a
      lower quality of life, a lower physical health, and more frequent feelings of
      depression compared with those who did perceive such body odor. CONCLUSION: Long
      term gastrointestinal and urinary symptoms after prostate irradiation are
      associated with the perception of fecal or urine body odor leading to a reduced
      quality of life. IMPLICATIONS FOR CANCER SURVIVORS: Disabling body odor after
      pelvic irradiation needs to be acknowledged in the clinic. Interventions to
      prevent long-term symptoms may serve the benefit of avoiding fecal or urine body
      odor after radiation therapy for prostate cancer.

PMID- 23975606
TI  - Autoimmunity in 2012.
AB  - The initiation and perpetuation of autoimmunity recognize numerous checkpoints,
      from the genomic susceptibility to the breakdown of tolerance. This latter
      phenomenon includes the loss of B cell anergy and T regulatory cell failure, as
      well as the production of autoantibodies and autoreactive T cells. These
      mechanisms ultimately lead to tissue injury via different mechanisms that span
      from the production of proinflammatory cytokines to the chemotaxis of immune
      cells to the target sites. The pathways to autoimmunity have been widely
      investigated over the past year and resulted in a number of articles in peer
      reviewed journals that has increased by nearly 10 % compared to 2011. We herein
      follow on the attempt to provide a brief discussion of the majority of articles
      on autoimmune diseases that were published in the major immunology journals in
      the previous solar year. The selection is necessarily arbitrary and may thus not
      be seen as comprehensive but reflects current research trends. Indeed, 2012
      articles were mostly dedicated to define new and old mechanisms with potential
      therapeutic implications in autoimmunity in general, though based on specific
      clinical conditions or animal models. As paradigmatic examples, the environmental
      influence on autoimmunity, Th17 changes modulating the autoimmune response, serum
      autoantibodies and B cell changes as biomarkers and therapeutic targets were
      major issues addressed by experimental articles in 2012. Further, a growing
      number of studies investigated the sex bias of autoimmunity and supported
      different working hypotheses to explain the female predominance, including sex
      chromosome changes and reproductive life factors. In conclusion, the resulting
      scenario illustrates that common factors may underlie different autoimmune
      diseases and this is well represented by the observed alterations in interferon
      alpha and TGFbeta or by the shared signaling pathways.

PMID- 23975612
TI  - Patient time and out-of-pocket costs for long-term prostate cancer survivors in
      Ontario, Canada.
AB  - PURPOSE: Time and out-of-pocket (OOP) costs can represent a substantial burden
      for cancer patients but have not been described for long-term cancer survivors.
      We estimated these costs, their predictors, and their relationship to financial
      income, among a cohort of long-term prostate cancer (PC) survivors. METHODS: A
      population-based, community-dwelling, geographically diverse sample of long-term
      (2-13 years) PC survivors in Ontario, Canada, was identified from the Ontario
      Cancer Registry and contacted through their referring physicians. We obtained
      data on demographics, health care resource use, and OOP costs through mailed
      questionnaires and conducted chart reviews to obtain clinical data. We compared
      mean annual time and OOP costs (2006 Canadian dollars) across clinical and
      sociodemographic characteristics and examined the association between costs and
      four groups of predictors (patient, disease, system, symptom) using two-part
      regression models. RESULTS: Patients' (N = 585) mean age was 73 years; 77 % were
      retired, and 42 % reported total annual incomes less than $40,000. Overall, mean
      time costs were $838/year and mean OOP costs were $200/year. Although generally
      low, total costs represented approximately 10 % of income for lower income
      patients. No demographic variables were associated with costs. Radical
      prostatectomy, younger age, poor urinary function, current androgen deprivation
      therapy, and recent diagnosis were significantly associated with increased
      likelihood of incurring any costs, but only urinary function significantly
      affected total amount. CONCLUSIONS: Time and OOP costs are modest for most long
      term PC survivors but can represent a substantial burden for lower income
      patients. Even several years after diagnosis, PC-specific treatments and
      treatment-related dysfunction are associated with increased costs. IMPLICATIONS
      FOR CANCER SURVIVORS: Time and out-of-pocket costs are generally manageable for
      long-term PC survivors but can be a significant burden mainly for lower income
      patients. The effects of PC-specific, treatment-related dysfunctions on quality
      of life can also represent sources of expense for patients.

PMID- 23975613
TI  - Persistent breast pain 5 years after treatment of invasive breast cancer is
      largely unexplained by factors associated with treatment.
AB  - PURPOSE: The aim of our study was to establish the prevalence of breast pain
      persisting 5 years after the initial treatment of breast cancer (BC) and the
      relationship between those persistent symptoms and general well-being. METHODS:
      The study involved women from Victoria, Australia, who had survived at least 5
      years from diagnosis, remained free from recurrence or new BC and completed the
      fifth annual follow-up questionnaire. Analysis involved both multivariable
      logistic and linear regression. RESULTS: Of 1,205 women, 45 % reported breast
      pain which persisted for at least 3 months following initial treatment, and of
      these, 80 % reported pain persisting for at least 5 years. The factor
      contributing most to the likelihood of persistent breast pain was current
      lymphedema; however, a full multivariable model explained <10 % of the likelihood
      of breast pain persisting for 5 years. The presence of breast pain at 5 years was
      associated with only a modest reduction in general well-being. CONCLUSIONS:
      Breast pain persisting for at least 5 years after treatment for BC is common. As
      the pain is largely unexplained by factors associated with the characteristics of
      the cancer or its treatment, the contribution of patient expectations to
      persistent breast pain may be considerable. IMPLICATIONS FOR CANCER SURVIVORS:
      Where persistent pain occurs, referral for the management of pain and, where
      appropriate, lymphedema is warranted.

PMID- 23975614
TI  - Thyroid hemorrhage causing airway obstruction after intravenous thrombolysis for
      acute ischemic stroke.
AB  - BACKGROUND: There are several life-threatening complications associated with
      intravenous thrombolysis after acute ischemic stroke such as symptomatic
      intracerebral hemorrhage, orolingual angioedema, or less frequent, bleedings of
      the mucosa or ecchymosis. Aside from these known critical incidents, rare and
      unfamiliar complications may be even more challenging, as they are unexpected and
      may mimic events that appear more frequently. We report a rare and unusual acute
      complication of intravenous thrombolysis with recombinant tissue plasminogen
      activator (rt-PA) (0.9 mg/kg) administered for acute ischemic stroke. METHODS:
      Medical records, radiologic imaging, and pathologic specimens were reviewed.
      RESULTS: A 86-year-old woman developed acute respiratory failure 20 h after
      thrombolysis with suspected angioedema triggered by intravenous rt-PA. The
      inspiratory stridor and dyspnea were unresponsive to bronchodilators,
      corticosteroids, and inhaled adrenaline. After endotracheal intubation,
      laryngoscopy showed no significant supraglottic narrowing. Thyroidal sonography
      and cervical computed tomography revealed a thyroidal mass causing a tracheal and
      vascular compression compatible with thyroidal hemorrhage. Sonography showed a
      nodular goiter of the right thyroid gland. A total thyroidectomy was performed
      and histologic analysis confirmed a hemorrhage of the right thyroidal lobe.
      CONCLUSIONS: Acute airway obstruction with respiratory failure due to thyroidal
      hemorrhage after intravenous thrombolysis is an important life-threatening
      complication, mimicking an anaphylactic reaction or a more frequent orolingual
      angioedema.

PMID- 23975616
TI  - Coronary CT angiography in the elderly.
AB  - People over 75 years of age represent a specific group of patients for which the
      clinician is often in doubt about what to do, whether additional diagnostic
      workup is helpful or a primary medical approach would suffice. However, this
      patient population is less prone to the long-term effects of radiation burden or
      contrast medium-induced nephropathy, and therefore it may be especially
      worthwhile to use advanced imaging techniques such as contrast-enhanced CT in
      these patients. The following cases illustrate two common diagnostic problems, in
      which coronary CT angiography decided the clinical course. 

PMID- 23975615
TI  - Bone flap necrosis after decompressive hemicraniectomy for malignant middle
      cerebral artery infarction.
AB  - BACKGROUND: Autologous bone flap reinsertion follows as a second surgical
      intervention after decompressive craniectomy in patients with malignant middle
      cerebral artery (MCA) infarction. In addition to surgery-related short-term
      complications, aseptic resorption of the reimplanted bone flap is a possible long
      term problem which has not yet been sufficiently elucidated in these patients.
      METHODS: A total of 109 patients who had undergone decompressive hemicraniectomy
      for malignant MCA infarction in our institution between September 1994 and
      December 2011 were included in the study. Clinical and radiological findings were
      retrieved retrospectively. Aseptic bone necrosis was classified into two
      categories based on computer tomographic features. RESULTS: A total of 76
      patients received their own cryoconserved bone flap (mean age 54.34 +/- 10.73
      years; 49 males). The overall short-term complication rate was 9.2 %. Bone flap
      necrosis occurred in 26 patients (22.8 %) with 7 flaps showing signs of
      surgically relevant type II necrosis after a median time of 14 months
      (interquartile range [IQR] 4-22). CONCLUSIONS: There is a noticeable complication
      rate in patients undergoing bone flap reinsertion after hemicraniectomy due to
      malignant MCA infarction. Aseptic bone necrosis represents a significant
      complication during long-term follow-up. The pathophysiological mechanisms remain
      unclear and more efforts should be undertaken to understand and possibly prevent
      this complication in these patients.

PMID- 23975617
TI  - The first year of the Venlo percutaneous coronary intervention program:
      procedural and 6-month clinical outcomes.
AB  - OBJECTIVES: Analysis of the first results of off-site percutaneous coronary
      interventions (PCI) and fractional flow reserve (FFR) measurements at VieCuri
      Medical Centre for Northern Limburg in Venlo. BACKGROUND: Off-site PCI is
      accepted in the European and American Cardiac Guidelines as the need for PCI
      increases and it has been proven to be a safe treatment option for acute coronary
      syndrome. METHODS: Retrospective cohort study reporting characteristics, PCI and
      FFR specifications, complications and 6-month follow-up for all consecutive
      patients from the beginning of off-site PCI in Venlo until July 2012. If
      possible, the data were compared with those of Medical Centre Alkmaar, the first
      off-site PCI centre in the Netherlands. RESULTS: Of the 333 patients, 19 (5.7 %)
      had a procedural complication. At 6 months, a major adverse cardiovascular event
      (MACE) occurred in 43 (13.1 %) patients. There were no deaths or emergency
      surgery related to the PCI or FFR procedures. There was no significant difference
      in occurrence of a MACE or adverse cerebral event between the Alkmaar and Venlo
      population in the 30-day follow-up. CONCLUSION: This study demonstrates off-site
      PCI at VieCuri Venlo to have a high success rate. Furthermore, there was a low
      complication rate, low MACE and no procedure-related mortality.

PMID- 23975618
TI  - Plasma extracellular vesicle protein content for diagnosis and prognosis of
      global cardiovascular disease.
AB  - Cardiovascular disease is a major public health problem worldwide. Its growing
      burden is particularly ominous in Asia, due to increasing rates of major risk
      factors such as diabetes, obesity and smoking. There is an urgent need for early
      identification and treatment of individuals at risk of adverse cardiovascular
      events. Plasma extracellular vesicle proteins are novel biomarkers that have been
      shown to be useful in the diagnosis, risk stratification and prognostication of
      patients with cardiovascular disease. Ongoing parallel biobank initiatives in
      European (the Netherlands) and Asian (Singapore) populations offer a unique
      opportunity to validate these biomarkers in diverse ethnic groups. 

PMID- 23975619
TI  - Exercise-based cardiac rehabilitation in patients with coronary heart disease: a
      practice guideline.
AB  - BACKGROUND: To improve the quality of exercise-based cardiac rehabilitation (CR)
      in patients with coronary heart disease (CHD) the CR guideline from the Dutch
      Royal Society for Physiotherapists (KNGF) has been updated. This guideline can be
      considered an addition to the 2011 Dutch Multidisciplinary CR guideline, as it
      includes several novel topics. METHODS: A systematic literature search was
      performed to formulate conclusions on the efficacy of exercise-based
      interventions during all CR phases in patients with CHD. Evidence was graded (1
      4) according the Dutch evidence-based guideline development (EBRO) criteria. In
      case of insufficient scientific evidence, recommendations were based on expert
      opinion. This guideline comprised a structured approach including assessment,
      treatment and evaluation. RESULTS: Recommendations for exercise-based CR were
      formulated covering the following topics: preoperative physiotherapy,
      mobilisation during the clinical phase, aerobic exercise, strength training, and
      relaxation therapy during the outpatient rehabilitation phase, and adoption and
      monitoring of a physically active lifestyle after outpatient rehabilitation.
      CONCLUSIONS: There is strong evidence for the effectiveness of exercise-based CR
      during all phases of CR. The implementation of this guideline in clinical
      practice needs further evaluation as well as the maintenance of an active
      lifestyle after supervised rehabilitation.

PMID- 23975620
TI  - Life is Movement (Aristotle, 4th century BC).

PMID- 23975621
TI  - Scientific education early in the curriculum using a constructivist approach on
      learning.
AB  - Physicians need to stay up-to-date with new developments in their field of
      expertise. This expectation has been made explicit by competency-based
      educational outcomes in the domain of scholar in the Dutch blueprint. There is a
      great diversity in teaching methods that aim to achieve a better understanding of
      scientific knowledge. Applying a constructivist approach to learning in acquiring
      research competencies we wonder how a research-intensive course is evaluated
      early in the curriculum and what learning gain students perceive. In a
      collaborative research-intensive course, the class of 300s-year students rated
      the quality of 150 preselected randomized controlled trials (RCT) using JAMA
      Users' Guides, and the pharmaceutical advertisements in which they were
      referenced. Each student rated two RCTs. Data were analyzed to answer a relevant
      research question. After the course students completed an evaluation survey. We
      did this in five consecutive years to capture student experience in relation to
      fostering a scientific mindset (n = 1,500). In addition we studied outcome of
      this scientific mindset as scientific output (publications) in journals. Survey
      data indicate that it is feasible to successfully implement a research-intensive
      course based on a large cohort using a constructivist paradigm early in the
      curriculum. Students consider it challenging and report high learning gain in
      several domains. Aggregated data have even led to four publications in journals.
      Implementing an active learning research experience early in the curriculum can
      foster student attitudes, provided the level of difficulty correctly matches the
      learners' prior knowledge. Further research is required to determine how to
      improve these active research curricula to maximize impact on learners. 

PMID- 23975622
TI  - Association of potentially functional genetic variants of PLCE1 with gallbladder
      cancer susceptibility in north Indian population.
AB  - BACKGROUND AND OBJECTIVES: Phospholipase C epsilon 1 (PLCE1) plays crucial roles
      in carcinogenesis and progression of esophageal and gastric cancers. In the
      present study, we investigated association of GWAS identified rs2274223 A>G and.
      rs7922612 T>C polymorphism of PLCE1 with susceptibility to gallbladder cancer
      (GBC). METHODS: The study involved genotyping of selected PLCE1 variants in 416
      GBC cases and 225 controls. Haplotype analysis was done by SNPStats. In silico
      analyses were performed using bioinformatic tools. RESULTS: PLCE1 rs2274223 [AG]
      and rs7922612 [CC] genotypes were found to be significantly associated with an
      increased risk of GBC [OR = 1.9, p = 0.002; OR = 2.0, p = 0.04, respectively].
      PLCE1 haplotype [Grs2274223-Crs7922612] also showed significant association with
      GBC [OR = 1.8, p = 0.04]. The association was significant in females and GBC
      patients with stones and female GBC patients with gallstones [OR = 2.6, p = 0.01;
      OR = 3.3, p = 0.007], respectively. However, no significant associations with
      other risk factors such as tobacco usage and age of onset were found. Functional
      prediction of rs2274223 A>G suggested change in protein coding and splicing
      regulation. CONCLUSION: The present study found a significant association of
      PLCE1 rs2274223 and rs7922612 polymorphisms with susceptibility to GBC probably
      through gallstone-mediated inflammatory pathway.

PMID- 23975623
TI  - Successful percutaneous endobiliary radiofrequency ablation for unresectable
      malignant biliary obstruction: a case report and review of the literature.

PMID- 23975624
TI  - Concern about security and privacy, and perceived control over collection and use
      of health information are related to withholding of health information from
      healthcare providers.
AB  - INTRODUCTION: This study assessed the perceptions and behaviors of US adults
      about the security of their protected health information (PHI). METHODS: The
      first cycle of the fourth wave of the Health Information National Trends Survey
      was analyzed to assess respondents' concerns about PHI breaches. Multivariate
      logistic regression was used to assess the effect of such concerns on disclosure
      of sensitive medical information to a healthcare professional (p<0.05). RESULTS:
      Most respondents expressed concerns about data breach when their PHI was being
      transferred between healthcare professionals by fax (67.0%; 95% CI 64.2% to
      69.8%) or electronically (64.5%; 95% CI 61.7% to 67.3%). About 12.3% (95% CI
      10.8% to 13.8%) of respondents had ever withheld information from a healthcare
      provider because of security concerns. The likelihood of information withholding
      was higher among respondents who perceived they had very little say about how
      their medical records were used (adjusted OR=1.42; 95% CI 1.03 to 1.96).
      CONCLUSIONS: This study underscores the need for enhanced measures to secure
      patients' PHI to avoid undermining their trust.

PMID- 23975626
TI  - Implementing health information exchange for public health reporting: a
      comparison of decision and risk management of three regional health information
      organizations in New York state.
AB  - Health information exchange (HIE) is a significant component of healthcare
      transformation strategies at both the state and national levels. HIE is expected
      to improve care coordination, and advance public health, but implementation is
      massively complex and involves significant risk. In New York, three regional
      health information organizations (RHIOs) implemented an HIE use case for public
      health reporting by demonstrating capability to deliver accurate responses to
      electronic queries via a set of services called the Universal Public Health Node.
      We investigated process and outcomes of the implementation with a comparative
      case study. Qualitative analysis was structured around a decision and risk
      matrix. Although each RHIO had a unique operational model, two common factors
      influenced risk management and implementation success: leadership capable of
      agile decision-making and commitment to a strong organizational vision. While all
      three RHIOs achieved certification for the public health reporting, only one has
      elected to deploy a production version. 

PMID- 23975625
TI  - Correlating electronic health record concepts with healthcare process events.
AB  - OBJECTIVE: To study the relation between electronic health record (EHR) variables
      and healthcare process events. MATERIALS AND METHODS: Lagged linear correlation
      was calculated between five healthcare process events and 84 EHR variables (24
      clinical laboratory values and 60 clinical concepts extracted from clinical
      notes) in a 24-year database. The EHR variables were clustered for each
      healthcare process event and interpreted. RESULTS: Laboratory tests tended to
      cluster together and note concepts tended to cluster together. Within each of
      those two classes, the variables clustered into clinically sensible groupings.
      The exact groupings varied from healthcare process event to event, with the
      largest differences occurring between inpatient events and outpatient events.
      DISCUSSION: Unlike previously reported pairwise associations between variables,
      which highlighted correlations across the laboratory-clinical note divide,
      incorporating healthcare process events appeared to be sensitive to the manner in
      which the variables were collected. CONCLUSION: We believe that it may be
      possible to exploit this sensitivity to help knowledge engineers select variables
      and correct for biases.

PMID- 23975627
TI  - HMG-CoA reductase inhibitors in chronic kidney disease.
AB  - The incidence of chronic kidney disease (CKD) is on the rise in the USA.
      Cardiovascular events are the leading cause of death in this patient population,
      therefore reducing the risk of these events has become a major focus. The aim of
      this review is to assess current literature on the use of statins in CKD and end
      stage renal disease. Cholesterol reduction is important in preventing the
      development and progression of coronary heart disease and its negative effects.
      Statins have been widely studied and proven to reduce cardiovascular risk in the
      general population. The information gained from trials has been extrapolated to
      special populations, including CKD, despite these patients often being excluded.
      However, recent studies have begun to focus on CKD, hemodialysis, and transplant
      patients and the use of cholesterol-lowering agents and the potential association
      with decreased cardiovascular events. In addition, due to the unique
      pharmacokinetic and pharmacodynamic changes that occur in these patients,
      choosing the appropriate cholesterol-lowering agent becomes important for both
      safety and efficacy. The complexity of CKD patients is an important consideration
      when choosing cholesterol-lowering medication. Patients with CKD are often on
      medications that may interact with many of the cholesterol-lowering agents.
      Ensuring drug interactions are minimized is essential to the prevention of
      adverse events from the medications. 

PMID- 23975628
TI  - Immunohistochemical localization of alpha2-adrenergic receptors in the neonatal
      rat cochlea and the vestibular labyrinth.
AB  - The alpha2-adrenergic receptors (alpha2-ARs), which mediate physiological
      responses to noradrenaline and adrenaline, are encoded by three different genes
      but all are coupled to the Gi/Go subfamily of G proteins. The present study
      investigated the localization of three subtypes, i.e., alpha2a-, alpha2b-, and
      alpha2c-ARs, in cochlea and vestibular labyrinth in rat in the early postnatal
      period by immunohistochemistry. The results showed that alpha2-ARs were widely
      distributed in regions, including the organ of Corti, spiral ganglion neurons,
      stria vascularis, crista ampullaris, Scarpa's ganglion, utricle, and Reissner's
      membrane. Furthermore, the cellular locations of alpha2-ARs between different
      cell subtypes as well as receptor subtypes and different observed time points
      also had diversity. alpha2a-AR mainly targeted to nuclei at postnatal ages (P)3.
      While at P(8), only ganglion neurons maintained this character whereas other cell
      types expressed alpha2a-AR mainly in plasma membrane. The alpha2b- and alpha2c
      ARs exhibited predominantly in plasma membrane. Compared with P(8), alpha2c-AR
      was not present at stria vascularis at P(3). Overall, our observations indicated
      that there was region-specific regulation of alpha2-ARs development in cochlea
      and vestibular labyrinth. In addition, the extensive expressions of alpha2-ARs
      established a significant foundation for the exploration of the function of
      alpha2-ARs in cochlea and vestibular labyrinth. 

PMID- 23975629
TI  - Structural and molecular alterations of primary afferent fibres in the spinal
      dorsal horn in vincristine-induced neuropathy in rat.
AB  - Vincristine is one of the most common anti-cancer drug therapies administered for
      the treatment of many types of cancer. Its dose-limiting side effect is the
      emergence of peripheral neuropathy, resulting in chronic neuropathic pain in many
      patients. This study sought to understand the mechanisms underlying the
      development of neuropathic pain by vincristine-induced neurotoxicity. We focused
      on signs of functional changes and revealed that deep layers of the spinal cord
      (III-IV) experience increased neuronal activity both in the absence of peripheral
      stimulation and, as a result of tactile mechanical stimulations. These laminae
      and superficial laminae I-II were also subject to structural changes as evidenced
      by an increase in immunoreactivity of Piccolo, a marker of active presynaptic
      elements. Further investigations performed, using DNA microarray technology,
      describe a large number of genes differentially expressed in dorsal root
      ganglions and in the spinal dorsal horn after vincristine treatment. Our study
      describes an important list of genes differentially regulated by vincristine
      treatment that will be useful for future studies and brings forward evidence for
      molecular and anatomical modifications of large diameter sensory neurons
      terminating in deep dorsal horn laminae, which could participate in the
      development of tactile allodynia. 

PMID- 23975630
TI  - Cost effectiveness of paliperidone palmitate for the treatment of schizophrenia
      in Germany.
AB  - BACKGROUND: Treatment with antipsychotic medication is an important element of
      relapse prevention in the management of schizophrenia, and can reduce inpatient
      stays. Recently, the long-acting atypical antipsychotic paliperidone long-acting
      injectable (PLAI), a once-monthly LAI antipsychotic, was approved for treatment
      of schizophrenia in Germany. OBJECTIVE: To estimate, based on a previously
      published model, the cost effectiveness of PLAI compared with other common
      antipsychotic treatment strategies in patients diagnosed with schizophrenia in
      Germany. METHODS: A Markov decision analytic model was adapted to the German
      healthcare system. The model considers the cost effectiveness for PLAI as a
      maintenance treatment for patients with schizophrenia from the payer perspective.
      The patients transition between eight health states on a monthly basis over a 5
      year time horizon. As therapeutic strategies, PLAI, quetiapine, risperidone long
      acting injections (RLAI), oral olanzapine, oral risperidone, zuclopenthixol
      decanoate, olanzapine long-acting injections (OLAI), oral typical and oral
      atypical were compared. Probability of relapse, level of adherence, side effects
      and treatment discontinuation were derived from the Swedish original model. Input
      factors regarding resource use and costs were estimated and adjusted for the
      German healthcare system. A probabilistic sensitivity analyses (PSA) using cost
      effectiveness scatter plots was performed to visualize the robustness of the
      results. RESULTS: In base-case scenario, PLAI is superior to RLAI in gained
      quality-adjusted life-years (QALYs) and avoided relapses. Relative to all other
      treatment strategies, PLAI is more effective with regard to gained QALYs and
      avoided relapses but results in higher treatment costs over a 5-year horizon in
      base-case scenario. The results were tested in PSA. If a cost-effectiveness
      threshold of <euro>30,000 is assumed, for example, PLAI can be considered to be
      cost effective compared with RLAI in about 92.5 % of cases regarding gained
      QALYs, and in 78.6 % of cases regarding avoided relapse. Compared with OLAI, in
      about 94.4 % of cases regarding gained QALYs and in 99.9 % of cases regarding
      avoided relapse, cost effectiveness can be considered. Comparing PLAI and
      zuclopenthixol decanoate, cost effectiveness can be assumed in about 90.4 % of
      cases regarding gained QALYs, and in all cases regarding avoided relapse.
      CONCLUSIONS: PLAI dominates RLAI and compared with the other treatment strategies
      PLAI has shown to be more effective but results in higher costs in base-case
      scenario.

PMID- 23975632
TI  - Surveillance mammography use after treatment of primary breast cancer and racial
      disparities in survival.
AB  - Racial and ethnic minority patients continue to die disproportionately from
      breast cancer compared with their white counterparts, even after adjusting for
      insurance status and income. No studies have examined whether surveillance
      mammography reduces racial disparities in survival among elderly breast cancer
      survivors following active treatment for breast cancer. This study included
      28,117 cases diagnosed with primary breast cancer at age 66 years and over,
      identified from SEER data during 1992-2005. Kaplan-Meier methods and Cox
      regression models were used for survival analysis. A higher proportion of whites
      received surveillance mammograms during the surveillance period compared with
      nonwhites: 71.7% of African-Americans, 72.5% of Hispanics, and 69.3% of Asians
      had mammograms compared with 74.9% of whites. In propensity-score-adjusted
      analysis, women who had a mammogram within 2 years were less likely (hazard ratio
      0.84; 95% CI 0.78-0.82) to die from any cause compared with women who did not
      have any mammograms during this time period. The hazard ratio of cancer-specific
      mortality elevated for Hispanics compared with whites (hazard ratio 1.5; 95% CI
      0.6-3.2) and was reduced after adjusting for surveillance mammography (hazard
      ratio 1.4; 95% CI 0.5-2.9). Similar pattern in the reduction in disease-specific
      hazard ratio was observed for blacks: After controlling for patient and tumor
      characteristics, hazard ratio was elevated but not significantly different from
      that in whites (hazard ratio 2.0; 95% CI 0.9-3.7), and hazard ratio adjusting for
      surveillance mammography further reduced the point estimate (hazard ratio 1.5;
      95% CI 0.7-2.8). Asian and Pacific Islanders and Hispanics appeared to have lower
      risks of all-cause mortality compared with whites after controlling for patient
      and tumor characteristics and surveillance mammogram received. Our findings
      indicates that while surveillance mammograms and physician visits may play a
      contributory role in achieving equal outcomes for breast cancer-specific
      mortality for women with breast cancer, searching for other factors that might
      help achieve national goals to eliminate racial disparities in healthcare, and
      outcomes is warranted.

PMID- 23975633
TI  - Long-term outcomes after curative resection for patients with macroscopically
      solitary hepatocellular carcinoma without macrovascular invasion and an analysis
      of prognostic factors.
AB  - The long-term outcome and prognostic factors after curative in patients with
      single hepatocellular carcinoma (HCC) without macrovascular invasion are still
      unclear. The objective of this study is to evaluate the effect of curative
      resection on survival and analyze the prognostic clinicopathologic factors,
      especially the presence of microvascular invasion (MVI), in these patients. Two
      hundred and sixty consecutive patients with single HCC without macrovascular
      invasion who underwent curative resection from December 2004 to December 2007
      were retrospectively reviewed in this study. Survival rates were calculated by
      using the Kaplan-Meier method. Univariate and multivariate analyses of 14
      clinicopathologic factors were performed to determine the significant prognostic
      factors. No patient died within 1 month after the operation. The 1-, 3-, and 5
      year overall survival rates after curative resection were 96.54, 83.46, and
      74.01%, respectively. Multivariate analysis revealed that only the presence of
      MVI was an independent negative prognostic factor affecting overall survival. The
      1-, 3-, and 5-year disease-free survival rates were 79.62, 62.69, and 56.01%,
      respectively. The presence of MVI was the only independent unfavorable prognostic
      factor for disease-free survival. According to our analysis, patients with single
      HCC without macrovascular invasion after curative resection can be expected to
      have considerable long-term survival. The presence of MVI was an independent
      negative prognostic factor for both overall survival and disease-free survival.
      To improve the prognosis, these patients should be followed up more carefully and
      might be good candidates for adjuvant therapy.

PMID- 23975634
TI  - EMT transcription factors: implication in osteosarcoma.
AB  - The primary malignant bone tumor, osteosarcoma, is a deadly disorder. Its
      etiology is complex, and treatment is mostly obscure. The transcription factors
      (TFs) involved in epithelial to mesenchymal transition (EMT) have significant
      role in osteosarcoma. A number of evidence suggests that overexpression of EMT
      TFs, such as Twist, Snails and Zebs, is involved in complex pathogenesis of
      osteosarcoma. Recent research studies have showed some extent of promise in
      osteosarcoma treatment by targeting these EMT-TFs. However, success in research
      on osteosarcoma-EMT-TFs axis is just in primary stage, and a long way to go.
      Targeting Twist, Snail or Zeb by specific molecules or chemotherapeutic agents
      may provide a new dimension in osteosarcoma treatment by controlling metastasis. 

PMID- 23975635
TI  - A survey of the microbial community in the rhizosphere of two dominant shrubs of
      the Negev Desert highlands, Zygophyllum dumosum (Zygophyllaceae) and Atriplex
      halimus (Amaranthaceae), using cultivation-dependent and cultivation-independent
      methods.
AB  - PREMISE OF THE STUDY: Plant roots comprise more than 50% of the plant's biomass.
      Part of that biomass includes the root microbiome, the assemblage of bacteria and
      fungi living in the 1-3 mm region adjacent to the external surface of the root,
      the rhizosphere. We hypothesized that the microorganisms living in the
      rhizosphere and in bulk soils of the harsh environment of the Negev Desert of
      Israel had potential for use as plant-growth-promoting bacteria (PGPB) to improve
      plant productivity in nutrient-poor, arid soils that are likely to become more
      common as the climate changes. * METHODS: We used cultivation-dependent methods
      including trap experiments with legumes to find nitrogen-fixing rhizobia,
      specialized culture media to determine iron chelation via siderophores and
      phosphate-solubilizing and cellulase activities; cultivation-independent methods,
      namely 16S rDNA cloning and sequencing; and also community-level physiological
      profiling to discover soil microbes associated with the Negev desert perennials
      Zygophyllum dumosum and Atriplex halimus during the years 2009-2010. * KEY
      RESULTS: We identified a number of PGPB, both epiphytes and endophytes, which fix
      nitrogen, chelate iron, solubilize phosphate, and secrete cellulase, as well as
      many other bacteria and some fungi, thereby providing a profile of the
      microbiomes that support the growth of two desert perennials. * CONCLUSION: We
      generated a snapshot of the microbial communities in the Negev Desert, giving us
      an insight in its natural state. This desert, like many arid environments, is
      vulnerable to exploitation for other purposes, including solar energy production
      and dry land farming.

PMID- 23975637
TI  - Regorafenib: a guide to its use in advanced gastrointestinal stromal tumor (GIST)
      after failure of imatinib and sunitinib.
AB  - Regorafenib (Stivarga((r))), a new inhibitor of multiple kinases, is indicated as
      third-line treatment in patients with locally advanced, unresectable or
      metastatic gastrointestinal stromal tumor (GIST) who have been previously treated
      with imatinib and sunitinib in the USA. In a phase III trial in patients with
      progressive GIST after failure of standard therapies, regorafenib plus best
      supportive care increased median progression-free survival by >5-fold relative to
      best supportive care alone. Although regorafenib is associated with several
      specific drug-related adverse events, it is reasonably well tolerated if
      recommendations for dose modifications (i.e. treatment interruption, dose
      reductions and/or permanent treatment discontinuation based on tolerability) and
      other precautions are followed. 

PMID- 23975636
TI  - Protective effect of melatonin on methamphetamine-induced apoptosis in glioma
      cell line.
AB  - Methamphetamine (METH) is a highly addictive drug causing neurodegenerative
      diseases. METH has been known to be neurotoxic by inducing oxidative stress, free
      radical, and pro-inflammatory cytokines. Previous studies have shown that METH
      could induce neuron and glial cell death, especially inducing glial cell-mediated
      neurotoxicity that plays a critical role in stress-induced central nervous system
      damage. Therefore, the aim of the present study is to explore the mechanisms of
      METH-induced cell death in the glial cell. METH-induced glial cells death is
      mediated via mitochondrial damage pathway. METH activates the upregulation of the
      Bax, cytochrome c, cleavage caspase 9 and 3 proteins, and downregulation of Bcl
      XL protein in cascade. Pretreatment with melatonin, a neurohormone secreted by
      the pineal gland, effectively reduced glial cell death. Moreover, melatonin
      increased the Bcl-XL/Bax ratio but reduced the level of cytochrome c, cleavage
      caspase 9 and 3 proteins. Therefore, these results demonstrated that melatonin
      could reduce the cytotoxic effect of METH by decreasing the mitochondrial death
      pathway activation in glial cells. This outcome suggests that melatonin might be
      beneficial as the neuroprotection in neurodegenerative diseases caused by METH or
      other pathogens. 

PMID- 23975639
TI  - Patient access to medical devices-what about Japan, the second largest medical
      device market?
AB  - Patients' access to innovative medical devices in Japan still shows the gap
      between the other countries. The cause of this device gap is researched from the
      prior published data. We searched the review time of new innovative devices by
      the Pharmaceuticals and Medical Devices Agency (PMDA) and the submission time lag
      compared with the US and EU from the prior published data. The average review
      time was 9.5 months and the total time from PMDA to introduction of the device to
      patients in Japan is almost similar to the US and the four European countries.
      However, the time lag of the file submission between Japan and the US was 2.42
      years, on average, between 2001 and 2009. The review time for new innovative
      medical devices by the PMDA has been improving year after year. On the contrary,
      the pre-submission delay still exists in Japan. 

PMID- 23975638
TI  - Carbon nanofiber electrode for neurochemical monitoring.
AB  - The ability to rapidly detect neurotransmitter release has broad implications in
      the study of a variety of neurodegenerative diseases. Electrochemical detection
      methods using carbon nanofiber nanoelectrodes integrated into the Wireless
      Instantaneous Neurotransmitter Concentration Sensing System (WINCS) offer many
      important advantages including biocompatibility, selectivity, sensitivity, and
      rapid adsorption kinetics. Carbon nanofiber nanoelectrodes exhibit greater
      selectivity and sensitivity in the electrochemical detection of neurotransmitters
      compared to macroelectrodes and are able to resolve a ternary mixture of dopamine
      (DA), serotonin (5-HT), and ascorbic acid as well as to detect individual
      neurotransmitters in concentrations as low as 50 nM for DA and 100 nM for 5-HT
      using differential pulse voltammetry. Adsorption kinetics studies and isopropyl
      alcohol treatments modeled on previous studies on carbon fiber microelectrodes
      were conducted to investigate the analogous properties on carbon nanofiber
      electrodes using fast-scan cyclic voltammetry with WINCS and showed analogous
      results in carbon nanofiber electrodes compared with carbon fiber
      microelectrodes.

PMID- 23975640
TI  - Successful percutaneous coronary intervention of a chronic totally occluded left
      anterior descending artery via an ipsilateral intraseptal channel using
      intravascular ultrasound-guided retrograde wire-crossing technique.
AB  - We herein report a 59-year-old man with a chronic totally occluded left anterior
      descending artery treated by percutaneous coronary intervention via an
      ipsilateral intraseptal channel using an intravascular ultrasound-guided
      retrograde wire-crossing technique. When an antegrade approach is not feasible or
      fails, a retrograde approach to a chronic totally occluded lesion is reasonable.
      However, a retrograde approach from the contralateral coronary artery is not
      always feasible. We herein report that an ipsilateral intraseptal channel can
      serve as one route by which to perform a retrograde approach to chronic totally
      occluded lesions of the left anterior descending artery.

PMID- 23975641
TI  - Firearms and suicide in the United States: is risk independent of underlying
      suicidal behavior?
AB  - On an average day in the United States, more than 100 Americans die by suicide;
      half of these suicides involve the use of firearms. In this ecological study, we
      used linear regression techniques and recently available state-level measures of
      suicide attempt rates to assess whether, and if so, to what extent, the well
      established relationship between household firearm ownership rates and suicide
      mortality persists after accounting for rates of underlying suicidal behavior.
      After controlling for state-level suicide attempt rates (2008-2009), higher rates
      of firearm ownership (assessed in 2004) were strongly associated with higher
      rates of overall suicide and firearm suicide, but not with nonfirearm suicide
      (2008-2009). Furthermore, suicide attempt rates were not significantly related to
      gun ownership levels. These findings suggest that firearm ownership rates,
      independent of underlying rates of suicidal behavior, largely determine
      variations in suicide mortality across the 50 states. Our results support the
      hypothesis that firearms in the home impose suicide risk above and beyond the
      baseline risk and help explain why, year after year, several thousand more
      Americans die by suicide in states with higher than average household firearm
      ownership compared with states with lower than average firearm ownership. 

PMID- 23975642
TI  - The prominent absence of Alfred Russel Wallace at the Darwin anniversaries in
      Germany in 1909, 1959 and 2009.
AB  - It is well known that the contribution of Alfred Russell Wallace (1823-1913) to
      the development of the "Darwinian" principle of natural selection has often been
      neglected. Here we focus on how the three anniversaries to celebrate the origin
      of the Darwin-Wallace theory in Germany in 1909, in 1959 in the divided country,
      as well as in 2009, have represented Charles Robert Darwin's and Alfred Russell
      Wallace's contributions. We have analyzed books and proceedings volumes related
      to these anniversaries, and the main result is that Wallace was almost always
      ignored, or only mentioned in passing. In 1909, Ernst Haeckel gave a talk in
      Jena, later published under the title The worldview of Darwin and Lamarck (Das
      Weltbild von Darwin und Lamarck), but not as the Darwin-Wallace concept. Haeckel
      mentions Wallace only once. In two important proceedings volumes from the 1959
      anniversaries, Wallace was ignored. The only fair treatment of Wallace is given
      in another book, a collection of documents edited by Gerhard Heberer, for which
      the author selected nine key documents and reprinted excerpts (1959). Three of
      them were articles by Wallace, including the Sarawak- and Ternate-papers of 1855
      and 1858, respectively. An analysis of the dominant themes during the
      celebrations of 2009 shows that none of the six topics had much to do with
      Wallace and his work. Thus, the tendency to exclude Alfred Russell Wallace is an
      international phenomenon, and largely attributable to the "Darwin industry". 

PMID- 23975643
TI  - The ornithologist Alfred Russel Wallace and the controversy surrounding the
      dinosaurian origin of birds.
AB  - Over many years of his life, the British naturalist Alfred Russel Wallace (1823
      1913) explored the tropical forests of Malaysia, collecting numerous specimens,
      including hundreds of birds, many of them new to science. Subsequently, Wallace
      published a series of papers on systematic ornithology, and discovered a new
      species on top of a volcano on Ternate, where he wrote, in 1858, his famous essay
      on natural selection. Based on this hands-on experience, and an analysis of an
      Archaeopteryx fossil, Wallace suggested that birds may have descended from
      dinosaurian ancestors. Here, we describe the "dinosaur-bird hypothesis" that
      originated with the work of Thomas H. Huxley (1825-1895). We present the strong
      evidence linking theropod dinosaurs to birds, and briefly outline the long and
      ongoing controversy around this concept. Dinosaurs preserving plumage, nesting
      sites and trace fossils provide overwhelming evidence for the dinosaurian origin
      of birds. Based on these recent findings of paleontological research, we conclude
      that extant birds indeed descended, with some modifications, from small, Mesozoic
      theropod dinosaurs. In the light of Wallace's view of bird origins, we critically
      evaluate recent opposing views to this idea, including Ernst Mayr's (1904-2005)
      arguments against the "dinosaur-bird hypothesis", and document that this famous
      ornithologist was not correct in his assessment of this important aspect of
      vertebrate evolution. 

PMID- 23975644
TI  - Alfred Russel Wallace and the destruction of island life: the Iguana tragedy.
AB  - The Galapagos Islands (Ecuador) are usually associated with the explorations and
      theoretical deductions of Charles Robert Darwin (1809-1882), but Alfred Russel
      Wallace (1823-1913) also investigated these islands and published several reports
      on the living world of this unique archipelago. In contrast to Darwin, Wallace
      described the destruction of natural ecosystems by humans and foresaw the
      resulting extinction of species. Here, we outline two case studies pertinent to
      Wallace's prediction. First, we summarize the behavior of the predator-naive
      marine iguanas (Amblyrhynchus cristatus) on the Galapagos Islands, which are
      threatened by feral dogs and cats imported by humans. We also describe the unique
      life cycle of the spiny-tailed iguana (Ctenosaura bakeri) from the island of
      Utila (Honduras), a rare species whose populations are declining because of
      habitat destructions. In contrast to these threatened, endemic island species,
      the Green iguana (Iguana iguana) is still widely distributed, although, as a
      result of de-forestation, in some areas of South America local populations have
      disappeared. We conclude that Wallace was correct in his prediction that, because
      of human activities, numerous species of animals and plants will be driven to
      extinction, notably on islands. 

PMID- 23975645
TI  - Comparison of early and late percutaneous endoscopic lumbar discectomy for lumbar
      disc herniation.
AB  - BACKGROUND: The optimal timing for percutaneous endoscopic lumbar discectomy
      (PELD) in cases of lumbar disc herniation (LDH) is debatable. This retrospective
      study sought to determine which category of PELD surgical intervention time
      resulted in greater improvement in clinical outcomes. METHODS: We retrospectively
      reviewed the medical records of 145 patients who underwent PELD for single-level
      LDH. The patients were divided into three categories according to the duration of
      leg pain before surgery, the early and late group being symptomatic for <=3
      months and >3 months, <=6 months and >6 months, <=12 months and >12 months.
      Surgical time, blood loss, postoperative hospital stay, hospitalization cost,
      rates of reoperation due to surgical failure, Macnab criteria assessment, visual
      analogue scale (VAS) of back pain, leg pain and numbness, Japanese orthopedic
      association low back pain score (JOA) before and after surgery were compared.
      RESULTS: No significant differences were found between the early and late groups
      according to different categories in patients' demographics, surgical time, blood
      loss, preoperative and postoperative VAS (lower-back pain, leg pain and numbness)
      scores, JOA scores and distribution of Macnab criteria assessment. Early PELD
      surgical intervention did not result in greater improvement of clinical outcomes.
      Later surgical intervention resulted in about one-third surgical failure rates
      for patients being symptomatic for >6 months (<=6 months, 11/96, 11.5 %; >6
      months, 2/49, 4.1 %; P = 0.245) and >12 months (<=12 months, 12/120, 10.0 %; >12
      months, 1/25, 4.0 %; P = 0.568) of the early surgical intervention groups.
      Significant difference was observed between the comorbidities and non
      comorbidities group in the rate of reoperation (P = 0.040). CONCLUSIONS: Early
      PELD surgical intervention did not result in greater improvement of clinical
      outcomes for patients with lumbar disc herniation. Later surgical intervention
      resulted in less failure rates for patients than the early surgical intervention
      groups. PELD performed when the leg pain before surgery being symptomatic for >6
      months may be good for avoiding surgical failure and reducing the duration of leg
      pain.

PMID- 23975646
TI  - Systematic review of the outcome of shunt surgery in idiopathic normal-pressure
      hydrocephalus.
AB  - INTRODUCTION: Early surgical series of shunt insertion for idiopathic normal
      pressure hydrocephalus reported a low rate of short-term improvement with a
      relatively high rate of mortality and morbidity; subsequently shunt insertion was
      recommended for patients in whom there is favourable risk-to-benefit ratio.
      METHODS: Bibliographic search for studies that objectively assessed the outcome
      following shunt insertion in idiopathic normal-pressure hydrocephalus was done;
      the aim was to estimate the outcome of shunt insertion in terms of improvement
      rates and associated mortality and morbidity. RESULTS: A total of 64 studies of
      3,063 patients were reviewed. Positive improvement following shunt insertion was
      reported in an average of 71 % of patients with an average 1 % mortality. Results
      from studies published in the last 5 years showed 82 % improvement following
      shunt insertion, mortality of 0.2 %, and combined common complications rate of
      8.2 %. CONCLUSION: When patients are properly selected, shunt insertion is a safe
      and effective management of idiopathic normal-pressure hydrocephalus with a
      prolonged positive outcome.

PMID- 23975647
TI  - Surgery of brainstem cavernous malformations.
AB  - BACKGROUND: Cavernomas are vascular hamartomas made up of thin-walled, grossly
      dilated blood vessels lined with endothelium. Between 4 and 35 % (mean 15 %) of
      cerebral cavernomas are located in the brainstem making resection of these
      lesions one of the most challenging tasks in neurosurgery. METHODS: Patients with
      cavernomas within the brainstem or deep supratentorial structures were chosen
      from our prospectively collected database of operated patients with brain
      cavernomas. The timespan of treatment was between January 1998 and June 2012.
      Primary outcome was defined as percentage of patients with favourable outcome
      (Glasgow Outcome Scale (GOS) 4 or 5) at 1 year. Secondary outcome was defined as
      operation-related morbidity and mortality (drop at least 1 point on GOS at 1
      year). RESULTS: A total of 37 patients underwent surgery. The mean age was 34.7
      +/- 11.7 years. The male to female ratio was 19:16. Thirty-two patients had a
      solitary lesion and 12 patients harboured multiple lesions. The Glasgow outcome
      score 4 or 5 was achieved after 34 operations (89.5 %). The mean follow-up was 39
      months. We experienced two early post-operative deaths (5.3 %) and decrease in
      the Glasgow outcome scale postoperatively in 4 patients (10.5 %). CONCLUSIONS: *
      Favourable outcome was achieved in 89.5 % of cases. * Although M&M appears to be
      relatively high, surgery is method of choice for surgically accessible lesion
      which has bled for the first time due to reported high rebleed rate and high
      probability of poor outcome after cavernoma rebleed. * Radiosurgery should be
      reserved for those lesions which are deemed unresectable and where surgical
      intervention is considered favourable to observation alone.

PMID- 23975648
TI  - Solitary clival plasmocytomas: Misleading clinical and radiological features of a
      rare pathology with a specific biological behaviour.
AB  - BACKGROUND: Tumours of the clivus are exceptionally rare, representing a
      diagnostic and a therapeutic challenge. Clival solitary plasmocytomas have been
      described only as single case reports or included in small clinical series with
      other intracranial location. METHODS: Authors report clinical, radiological, and
      survival data of four patients, who underwent surgery for clival plasmocytomas
      between 1989 and 2012 in a single centre. Current knowledge about solitary
      plasmocytomas of the clivus are reviewed. RESULTS: Follow-up time was 54 months
      (range: 9-165). Mean age of patient was 57 years, no gender predilection was
      observed. Main symptoms were headache (75 %) and double vision (75 %), due to
      third or sixth cranial nerve palsy. Mean time to diagnosis was 8.2 months. All
      patients underwent surgery as primary treatment, through either a transsphenoidal
      (75 %) or a transmaxillary approach (25 %). In all cases adjuvant conventional
      radiotherapy was performed with a median delivered dose of 45 Gy. Only one case
      of progression into multiple myeloma was observed 13 months after surgery, and
      the patient died 9 months later. No other recurrences or progression were
      observed. Mean overall survival and progression free survival time were,
      respectively, 54 and 51.7 months. CONCLUSIONS: Although extremely rare, clival
      plasmocytomas have to be considered in the differential diagnosis of a solitary
      clival lesion. Biological and clinical features of these tumours strongly differ
      from those of similar lesions in other part of the body. Early diagnosis,
      extensive tumour removal, opportune indication of adjuvant treatment with
      radiotherapy and chemotherapy are the keys to manage these cases.

PMID- 23975649
TI  - Tremor reduction and quality of life after deep brain stimulation for multiple
      sclerosis-associated tremor.
AB  - BACKGROUND: Tremor is an important cause of disability and poor quality of life
      amongst multiple sclerosis (MS) patients. We assessed the outcomes of ventral
      intermediate (VIM) nucleus deep brain stimulation for the treatment of multiple
      sclerosis (MS)-associated tremor at a single centre in a prospective fashion.
      METHODS: Sixteen patients (9 female, 7 male) with a mean age of 41.7 years (range
      24-59) underwent surgery. The median duration of MS prior to surgery was 6.5
      years and median duration of tremor prior to surgery was 4 years. Case selection
      was by multidisciplinary assessment with carers, therapists, neurosurgeons and
      movement disorder neurologists. Tremor was scored pre-operatively and at 6 to 12
      months post operatively using Bain and/or Fahn-Tolosa-Marin systems. The Euro-Qol
      5D tool was used to assess quality of life before and after surgery. RESULTS: The
      mean tremor reduction was 39 % with a range between 0 and 87 %. Five of 16
      patients achieved at least 50 % tremor reduction and 11 of 16 achieved at least
      30 % tremor reduction at last follow up, mean 11.6 months (range 3-80). Tremor
      was significantly reduced as rated by Bain scores (Wilcoxon matched pairs, Z =
      3.07, p = .002) and tended to significance as rated by Fahn scores (Wilcoxon
      matched pairs, Z = 1.85, p = 0.06). Sub-analysis of activities of daily living
      measures from the Fahn system showed post operative improvement in feeding
      (statistically significant), hygiene, dressing, writing and working. Mean visual
      analogue scores (0-100) of patient reported well-being increased from 54.6 to
      57.4 post operatively with a trend to significance (Student's t-test, t = 1.26, p
      = 0.2). Euro-Qol 5D utility values increased following surgery with a trend to
      significance which was greater in the group with at least 50 % tremor reduction
      than in those with none or at least 30 % tremor reduction. CONCLUSIONS: VIM DBS
      may reduce severe, disabling tremor in patients with MS. This tremor reduction
      tends to be associated with improved quality of life and function in those who
      respond. Patient reported outcome measures may not correlate with physician rated
      clinical outcome such as tremor scoring systems and more subtle assessment of
      these patients is required.

PMID- 23975650
TI  - The endoscopic intraventricular management of pineal cysts: a minimally invasive
      modus operandi.
AB  - BACKGROUND: The management of pineal cysts is still debatable, especially for
      asymptomatic incidental ones. For symptomatic cysts associated with
      hydrocephalus, the surgical management is mandatory and may include either
      classical microsurgical approaches to the pineal region or endoscopic trans
      ventricular approaches in a minimally invasive philosophy. METHOD: The authors
      expose a stepwise technique to treat a pineal cyst associated with an obstructive
      hydrocephalus in one procedure gathering a third ventriculostomy followed by an
      intraventricular marsupialisation of the pineal cyst. CONCLUSION: This endoscopic
      approach allows the treatment of the hydrocephalus and the pineal cyst in one
      short minimally invasive procedure.

PMID- 23975651
TI  - Effect of melatonin supplementation and cross-fostering on renal glutathione
      system and development of hypertension in spontaneously hypertensive rats.
AB  - Antenatal and postnatal environments are hypothesised to influence the
      development of hypertension. This study investigates the synergistic effect of
      cross-fostering and melatonin supplementation on the development of hypertension
      and renal glutathione system in spontaneously hypertensive rats (SHR). In one
      experiment, 1-day-old male SHR pups were fostered to either SHR (shr-SHR) or
      Wistar-Kyoto rats, (shr-WKY). In a concurrent experiment, SHR dams were given
      melatonin in drinking water (10 mg/kg body weight) from day 1 of pregnancy.
      Immediately following delivery, 1-day-old male pups were fostered either to SHR
      (Mel-shr-SHR) or WKY (Mel-shr-WKY) dams receiving melatonin supplementation until
      weaning on day 21. Upon weaning, melatonin supplementation was continued to these
      pups until the age of 16 weeks. Systolic blood pressures (SBP) were recorded at
      the age of 4, 6, 8, 12 and 16 weeks. Renal antioxidant activities were measured.
      Mean SBP of shr-WKY, Mel-shr-SHR and Mel-shr-WKY was significantly lower than
      that in shr-SHR until the age of 8 weeks. At 12 and 16 weeks of age, mean SBP of
      Mel-shr-WKY was lower than those in non-treated shr-SHR and shr-WKY pups but was
      not significantly different from that in Mel-shr-SHR. Renal glutathione
      peroxidase (GPx) and glutathione S-transferase (GST) activities were
      significantly higher in Mel-shr-SHR and Mel-shr-WKY at 16 weeks of age. It
      appears that combination of cross-fostering and melatonin supplementation exerts
      no synergistic effect on delaying the rise in blood pressure in SHR. The elevated
      GPx and GST activities are likely to be due to the effect of melatonin
      supplementation.

PMID- 23975652
TI  - Metabolomics study of type 2 diabetes using ultra-performance LC-ESI/quadrupole
      TOF high-definition MS coupled with pattern recognition methods.
AB  - Type 2 diabetes (T2D), called the burden of the twenty-first century, is growing
      with an epidemic rate. Here, we explored the differences in metabolite
      concentrations between T2D patients and healthy volunteers. Metabolomics
      represents an emerging discipline concerned with comprehensive analysis of small
      molecule metabolites and provides a powerful approach to discover biomarkers in
      biological systems. The acquired data were analyzed by ultra-performance liquid
      chromatography-electrospray ionization/quadrupole time-of-flight high-definition
      mass spectrometry coupled with pattern recognition approach [principal component
      analysis (PCA) and partial least squares discriminant analysis (PLS-DA)] to
      identify potential disease-specific biomarkers. PCA showed satisfactory
      clustering between patients and healthy volunteers. Biomarkers reflected the
      biochemical events associated with early stages of T2D which were observed in PLS
      DA loading plots. These urinary differential metabolites, such as adiponectin,
      acylcarnitines, citric acid, kynurenic acid, 3-indoxyl sulfate, urate, and
      glucose, were identified involving several key metabolic pathways such as taurine
      and hypotaurine metabolism; cysteine and methionine metabolism; valine, leucine,
      and isoleucine biosynthesis metabolism, etc. Our data suggest that robust
      metabolomics has the potential as a noninvasive strategy to evaluate the early
      diagnosis of T2D patients and provides new insight into pathophysiologic
      mechanisms and may enhance the understanding of its cause of disease. 

PMID- 23975653
TI  - Capture mechanism in Palaeotropical pitcher plants (Nepenthaceae) is constrained
      by climate.
AB  - BACKGROUND AND AIMS: Nepenthes (Nepenthaceae, approx. 120 species) are
      carnivorous pitcher plants with a centre of diversity comprising the Philippines,
      Borneo, Sumatra and Sulawesi. Nepenthes pitchers use three main mechanisms for
      capturing prey: epicuticular waxes inside the pitcher; a wettable peristome (a
      collar-shaped structure around the opening); and viscoelastic fluid. Previous
      studies have provided evidence suggesting that the first mechanism may be more
      suited to seasonal climates, whereas the latter two might be more suited to
      perhumid environments. In this study, this idea was tested using climate envelope
      modelling. METHODS: A total of 94 species, comprising 1978 populations, were
      grouped by prey capture mechanism (large peristome, small peristome, waxy,
      waxless, viscoelastic, non-viscoelastic, 'wet' syndrome and 'dry' syndrome).
      Nineteen bioclimatic variables were used to model habitat suitability at approx.
      1 km resolution for each group, using Maxent, a presence-only species
      distribution modelling program. KEY RESULTS: Prey capture groups putatively
      associated with perhumid conditions (large peristome, waxless, viscoelastic and
      'wet' syndrome) had more restricted areas of probable habitat suitability than
      those associated putatively with less humid conditions (small peristome, waxy,
      non-viscoelastic and'dry' syndrome). Overall, the viscoelastic group showed the
      most restricted area of modelled suitable habitat. CONCLUSIONS: The current study
      is the first to demonstrate that the prey capture mechanism in a carnivorous
      plant is constrained by climate. Nepenthes species employing peristome-based and
      viscoelastic fluid-based capture are largely restricted to perhumid regions; in
      contrast, the wax-based mechanism allows successful capture in both perhumid and
      more seasonal areas. Possible reasons for the maintenance of peristome-based and
      viscoelastic fluid-based capture mechanisms in Nepenthes are discussed in
      relation to the costs and benefits associated with a given prey capture strategy.

PMID- 23975655
TI  - Pharmaceutical costs of assisted reproduction in Spain.
AB  - BACKGROUND: Assisted reproduction is one of the health services currently being
      considered for possible limitation or exclusion from the public health services
      portfolio in Spain. One of the main reasons claimed for this is the impact on the
      budget for pharmaceutical expenditure. OBJECTIVE: The objective of this study was
      to assess the significance of the pharmaceutical costs of assisted reproduction
      in Spain. METHODS: This study focused on medical practice in Spain, and is based
      on the opinions of experts in assisted reproduction and the results provided by
      professional societies' publications. The reference year is 2012 and the setting
      was secondary care. We have included all existing pharmaceutical modalities for
      assisted reproduction, as well as the most common drug for each modality. We have
      considered the pharmaceutical cost per cycle for artificial insemination, in
      vitro fertilisation with or without intracytoplasmic sperm injection (IVF_ICSI),
      and cryotransfer and donated fresh oocytes reception. RESULTS: In Spain,
      artificial insemination has a pharmaceutical cost per cycle of between ?69.36 and
      ?873.79. This amounts to an average cycle cost of ?364.87 for partner's sperm and
      ?327.10 for donor sperm. The pharmaceutical cost of IVF_ICSI ranges between
      ?278.16 and ?1,902.66, giving an average cost per cycle of ?1,139.65. In the case
      of cryotransfer and donated fresh oocytes reception, the pharmaceutical cost per
      cycle is between ?22.61 and ?58.73, yielding an average cost of ?40.67. The
      budgetary impact of pharmaceutical expenditure for assisted reproduction in Spain
      for the year 2012 was estimated at ?98.7 million. CONCLUSION: In Spain, the total
      pharmaceutical cost of assisted reproduction is substantial. According to our
      results, we can say that about 29% of the total pharmaceutical expenditure for
      assisted reproduction techniques is funded by the National Health System and the
      rest represents 2.4% of the total annual out-of-pocket family expenditure on
      drugs.

PMID- 23975654
TI  - Pharmacokinetic drug interactions involving vortioxetine (Lu AA21004), a
      multimodal antidepressant.
AB  - BACKGROUND AND OBJECTIVE: The identification and quantification of potential drug
      drug interactions is important for avoiding or minimizing the interaction-induced
      adverse events associated with specific drug combinations. Clinical studies in
      healthy subjects were performed to evaluate potential pharmacokinetic
      interactions between vortioxetine (Lu AA21004) and co-administered agents,
      including fluconazole (cytochrome P450 [CYP] 2C9, CYP2C19 and CYP3A inhibitor),
      ketoconazole (CYP3A and P-glycoprotein inhibitor), rifampicin (CYP inducer),
      bupropion (CYP2D6 inhibitor and CYP2B6 substrate), ethinyl
      estradiol/levonorgestrel (CYP3A substrates) and omeprazole (CYP2C19 substrate and
      inhibitor). METHODS: The ratio of central values of the test treatment to the
      reference treatment for relevant parameters (e.g., area under the plasma
      concentration-time curve [AUC] and maximum plasma concentration [C max]) was used
      to assess pharmacokinetic interactions. RESULTS: Co-administration of
      vortioxetine had no effect on the AUC or C max of ethinyl
      estradiol/levonorgestrel or 5'-hydroxyomeprazole, or the AUC of bupropion; the 90
      % confidence intervals for these ratios of central values were within 80-125 %.
      Steady-state AUC and C max of vortioxetine increased when co-administered with
      bupropion (128 and 114 %, respectively), fluconazole (46 and 15 %, respectively)
      and ketoconazole (30 and 26 %, respectively), and decreased by 72 and 51 %,
      respectively, when vortioxetine was co-administered with rifampicin. Concomitant
      therapy was generally well tolerated; most adverse events were mild or moderate
      in intensity. CONCLUSION: Dosage adjustment may be required when vortioxetine is
      co-administered with bupropion or rifampicin.

PMID- 23975656
TI  - Pharmacokinetics and safety of golimumab in healthy Chinese subjects following a
      single subcutaneous administration in a randomized phase I trial.
AB  - BACKGROUND AND OBJECTIVES: Golimumab is an anti-tumor necrosis factor-alpha human
      immunoglobulin G1kappa monoclonal antibody that is efficacious for the treatment
      of moderate to severe rheumatoid arthritis, psoriatic arthritis, and ankylosing
      spondylitis in adults. The objective of this study was to assess the
      pharmacokinetic characteristics of golimumab in healthy male Chinese subjects
      following a single subcutaneous (SC) administration of golimumab 50 or 100 mg.
      The safety, tolerability, and immunogenicity of a single SC administration of
      golimumab in Chinese subjects were also evaluated. METHODS: This was a phase I,
      randomized, open-label, single-dose, single-period, single-center study. Twenty
      four healthy male Chinese subjects were randomized (1:1) to receive a single SC
      administration of golimumab 50 or 100 mg. Serial blood samples for the
      measurement of serum golimumab concentrations were collected and analyzed using a
      validated electrochemiluminescent immunoassay method. The pharmacokinetic
      parameters [maximum observed serum concentration (C(max)), time to reach C(max)
      (t(max)), area under the serum concentration-time curve from time zero to
      infinity (AUCinfinity), and terminal half-life (t(1/2))] of golimumab were
      derived using a noncompartmental analysis. RESULTS: Following a single SC
      administration of golimumab 50 or 100 mg in Chinese male subjects (age 19-41
      years, body weight 60-76 kg), mean +/- standard deviation C(max) (3.6 +/- 1.6 and
      7.5 +/- 1.4 MUg/mL, respectively) and AUCinfinity (59.8 +/- 19.8 and 132.8 +/-
      27.0 MUg.day/mL, respectively) increased in a dose-proportional manner. The
      median t(max) was in the range of 4.5-5.0 days, and the mean t(1/2) was in the
      range of 10.8-11.9 days. Among 24 subjects, 23 had appropriate samples for
      evaluation of antibodies to golimumab, and one subject (1/23, 4.3%) in the 100-mg
      group tested positive. Three mild adverse events were reported (infected
      sebaceous cyst, upper respiratory tract infection, and headache), all in the 50
      mg group; none were considered to be related to the study agent. CONCLUSIONS:
      Golimumab exhibited linear pharmacokinetics at dose levels of 50 and 100 mg
      following a single SC administration in healthy Chinese subjects. Single SC
      administrations of golimumab 50 or 100 mg were considered to be generally well
      tolerated. The results from this study indicate that there are no apparent ethnic
      differences in the pharmacokinetics of golimumab between Chinese and Caucasian
      subjects.

PMID- 23975657
TI  - Effective achievement of hemoglobin stability with once-monthly C.E.R.A. in
      peritoneal dialysis patients: a prospective study.
AB  - BACKGROUND: Correction of low hemoglobin (Hb) levels is associated with improved
      survival and greater quality of life in dialysis patients, but frequent
      administration of erythropoiesis stimulating agent (ESA) therapy is
      unsatisfactory for peritoneal dialysis patients. OBJECTIVE: The objective of this
      study was to assess Hb stability in an unselected population of maintenance
      peritoneal dialysis patients receiving once-monthly treatment with C.E.R.A., a
      continuous erythropoietin receptor activator. METHODS: In a prospective, non
      interventional, single-arm study at 33 Germany dialysis centers, peritoneal
      dialysis patients with or without ESA treatment prior to study entry received
      once-monthly treatment with C.E.R.A. Hb stability was assessed by the proportion
      of patients for whom all measured Hb values during months 6-8 (the evaluation
      phase) were within the range 11-12, 11-13, 10-12 or 11-12.5 g/dL. RESULTS: 220
      patients received at least one dose of C.E.R.A. During the evaluation phase, 185
      patients provided >=1 Hb measurement (efficacy population) and 162 patients
      provided >=2 Hb measurements (the modified efficacy population). The mean (SD)
      time between C.E.R.A. doses was 28.2 (7.2) days and mean (SD) C.E.R.A. dose was
      109 (57) MUg per application. Mean (SD) Hb level was 11.1 (1.4) g/dL at baseline
      and 11.5 (1.3) g/dL at the end of the study (modified efficacy population). The
      primary efficacy variable, all measured Hb values in the range 11-12 g/dL, was
      18.4 % (34/185) and 14.8 % (24/162) in the efficacy and modified efficacy
      populations, respectively. The mean (SD) maximum intra-individual fluctuation in
      Hb level was 0.56 (0.50) g/dL in the efficacy population and 0.58 (0.49) g/dL in
      the modified efficacy population, with maximum intra-individual fluctuation <=1
      g/dL in 85.4 % (158/185) and 83.3 % (135/162) of patients, respectively. No
      adverse drug reactions were reported during the study. CONCLUSION: In this large
      population of maintenance peritoneal dialysis patients, once-monthly
      administration of C.E.R.A. achieved a high degree of Hb stability and was well
      tolerated.

PMID- 23975658
TI  - Ovarian cancer: Deaf and hearing women's knowledge before and after an
      educational video.
AB  - Members of the Deaf community report language and cultural barriers to accessing
      health information and care. This study evaluated whether an ovarian cancer
      education video in American Sign Language with English captioning and voice-over
      could close the anticipated knowledge gap between Deaf and hearing women's cancer
      knowledge. Consented Deaf (n = 55) and hearing (n = 52) women's General, Ovarian,
      and Total Cancer Knowledge were assessed before and after viewing the video. At
      baseline, hearing women demonstrated significantly higher General, Ovarian, and
      Total Cancer Knowledge scores than Deaf women. By the post-test, all of Deaf
      women's knowledge scores had increased, closing the baseline gap. However,
      hearing women's post-video knowledge had also increased, thereby creating a new
      knowledge gap. The ovarian cancer education video offers an effective method to
      increase ovarian and general cancer knowledge for Deaf and hearing women.

PMID- 23975659
TI  - Tobacco cessation interventions for young people.
AB  - BACKGROUND: Most tobacco control programmes for adolescents are based around
      prevention of uptake, but teenage smoking is still common. It is unclear if
      interventions that are effective for adults can also help adolescents to quit.
      This is the second update of a Cochrane review first published in 2006.
      OBJECTIVES: To evaluate the effectiveness of strategies that help young people to
      stop smoking tobacco. SEARCH METHODS: We searched the Cochrane Tobacco Addiction
      Group's Specialized Register in February 2013. This includes reports for trials
      identified in the Cochrane Central Register of Controlled Trials (CENTRAL),
      MEDLINE, EMBASE and PsyclNFO. SELECTION CRITERIA: We included randomized
      controlled trials, cluster-randomized controlled trials and other controlled
      trials recruiting young people, aged less than 20, who were regular tobacco
      smokers. We included any interventions; these could include pharmacotherapy,
      psycho-social interventions and complex programmes targeting families, schools or
      communities. We excluded programmes primarily aimed at prevention of uptake. The
      primary outcome was smoking status after at least six months follow-up among
      those who smoked at baseline. DATA COLLECTION AND ANALYSIS: Both authors
      independently assessed the eligibility of candidate trials and extracted data.
      Included studies were evaluated for risk of bias using standard Cochrane
      methodology. Where meta-analysis was appropriate, we estimated pooled risk ratios
      using a Mantel-Haenszel fixed-effect method, based on the quit rates at longest
      follow-up. MAIN RESULTS: Twenty-eight trials involving approximately 6000 young
      people met our inclusion criteria (12 cluster-randomized controlled trials, 14
      randomized controlled trials and 2 controlled trials). The majority of studies
      were judged to be at high or unclear risk of bias in at least one domain. Many
      studies combined components from various theoretical backgrounds to form complex
      interventions.The majority used some form of motivational enhancement combined
      with psychological support such as cognitive behavioural therapy (CBT) and some
      were tailored to stage of change using the transtheoretical model (TTM). Three
      trials based mainly on TTM interventions achieved moderate long-term success,
      with a pooled risk ratio (RR) of 1.56 at one year (95% confidence interval (CI)
      1.21 to 2.01). The 12 trials that included some form of motivational enhancement
      gave an estimated RR of 1.60 (95% CI 1.28 to 2.01). None of the 13 individual
      trials of complex interventions that included cognitive behavioural therapy
      achieved statistically significant results, and results were not pooled due to
      clinical heterogeneity. There was a marginally significant effect of pooling six
      studies of the Not on Tobacco programme (RR of 1.31, 95% CI 1.01 to 1.71),
      although three of the trials used abstinence for as little as 24 hours at six
      months as the cessation outcome. A small trial testing nicotine replacement
      therapy did not detect a statistically significant effect. Two trials of
      bupropion, one testing two doses and one testing it as an adjunct to NRT, did not
      detect significant effects. Studies of pharmacotherapies reported some adverse
      events considered related to study treatment, though most were mild, whereas no
      adverse events were reported in studies of behavioural interventions. AUTHORS'
      CONCLUSIONS: Complex approaches show promise, with some persistence of abstinence
      (30 days point prevalence abstinence or continuous abstinence at six months),
      especially those incorporating elements sensitive to stage of change and using
      motivational enhancement and CBT. Given the episodic nature of adolescent
      smoking, more data is needed on sustained quitting. There were few trials with
      evidence about pharmacological interventions (nicotine replacement and
      bupropion), and none demonstrated effectiveness for adolescent smokers. There is
      not yet sufficient evidence to recommend widespread implementation of any one
      model. There continues to be a need for well-designed adequately powered
      randomized controlled trials of interventions for this population of smokers.

PMID- 23975660
TI  - Comparative efficacy of guanfacine extended release versus atomoxetine for the
      treatment of attention-deficit/hyperactivity disorder in children and
      adolescents: applying matching-adjusted indirect comparison methodology.
AB  - BACKGROUND: No head-to-head clinical trials have been published comparing
      guanfacine extended release (GXR) and atomoxetine (ATX): two nonstimulants
      approved for the treatment of attention-deficit/hyperactivity disorder (ADHD).
      However, other study designs or methods could be used to indirectly compare these
      two medications. Matching-adjusted indirect comparison (MAIC) is a recent
      methodology that utilizes individual patient data (IPD) from clinical trials for
      one treatment and published aggregate data from another treatment to estimate the
      relative efficacy of both, providing rapid, reliable comparative efficacy
      results. OBJECTIVE: The aim of this study was to compare the efficacy of GXR and
      ATX for the treatment of ADHD using MAIC. STUDY DESIGN: A systematic literature
      search was conducted to identify ATX and GXR trials published through December
      2012. Studies were selected for MAIC analyses on the basis of having comparable
      trial characteristics and study designs. Summary data from selected ATX trials
      and IPD from selected GXR trials were used. MAIC methodology ensured comparable
      populations: target doses for the 'base case' comparison were selected on the
      basis of maximum effective dosage ranges from the US FDA-approved product labels
      (GXR 0.09-0.12 mg/kg/day, ATX 1.2 mg/kg/day for children and adolescents weighing
      <=70 kg). Individuals from GXR trials were selected if they matched
      inclusion/exclusion criteria from selected ATX trials; selected GXR IPD were then
      re-weighted to match the published ATX trial mean baseline characteristics and
      placebo outcomes. Sensitivity analyses were conducted, examining different dosage
      ranges and repeating the analysis in a larger number of trials, allowing for
      larger and more heterogeneous trial populations. MAIN OUTCOME MEASURE: The
      primary outcome measure was change in ADHD Rating Scale IV (ADHD-RS-IV) total
      score. RESULTS: Using MAIC in the base case comparison, significantly greater
      reductions in mean (standard error; SE) ADHD-RS-IV total scores from baseline to
      end of study were observed in patients treated with GXR relative to ATX [-7.0
      (2.2); p < 0.01]. Significantly greater reductions for GXR over ATX were also
      demonstrated for hyperactivity/impulsivity [-3.8 (1.2); p < 0.01] and inattention
      [-3.2 (1.3); p < 0.05] subscales of the ADHD-RS-IV. Similar results were observed
      in MAIC sensitivity analyses evaluating other dosage ranges and using more
      heterogeneous trial populations (e.g., larger randomized sample, broader subject
      weight range, additional trials). Mean (SE) decreases in ADHD-RS-IV total scores
      were greater for GXR relative to ATX when including IPD for those administered
      GXR at lower than target dosage (0.075-0.090 mg/kg/day) compared with ATX at
      target dosage (1.2 mg/kg/day), with a relative improvement of -6.0 (2.7) (p <
      0.05). Reductions in ADHD-RS-IV total scores were also greater for GXR in another
      MAIC examining GXR at target dosage (0.09-0.12 mg/kg/day) and a broader range of
      ATX dosages (including three additional trials evaluating ATX >=1.2 mg/kg/day);
      relative improvement for GXR versus ATX administered at target dosage or higher
      was -7.6 (1.4) (p < 0.01). CONCLUSION: After adjusting for difference in baseline
      trial characteristics using MAIC, GXR appears to be more efficacious than ATX for
      the treatment of ADHD. Results were consistent in a variety of dosage range
      comparisons and within increasingly heterogeneous trial populations.

PMID- 23975661
TI  - Dexmedetomidine for the treatment of alcohol withdrawal syndrome: rationale and
      current status of research.
AB  - Dexmedetomidine is currently used in the US in the treatment of alcohol
      withdrawal syndrome (AWS) in the intensive care unit (ICU) setting, although data
      to support this practice are limited. Dexmedetomidine targets the noradrenergic
      system, an important but frequently overlooked secondary mechanism in the
      development of AWS, and, in doing so, may reduce the need for excessive
      benzodiazepine use which can increase the risk of gamma-aminobutyric acid (GABA)
      mediated deliriogenesis and respiratory depression. The purpose of this narrative
      review is to evaluate available literature reporting on the safety and efficacy
      of dexmedetomidine for AWS in the ICU setting. An English-language MEDLINE search
      (1966 to July 2013) was performed to identify articles evaluating the efficacy
      and safety of dexmedetomidine for AWS. Case series, case reports and controlled
      trials were evaluated for topic relevance and clinical applicability. Reference
      lists of articles retrieved through this search were reviewed to identify any
      relevant publications. Studies focusing on the safety and efficacy of
      dexmedetomidine for AWS in humans were selected. Studies were included if they
      were published as full articles; abstracts alone were not included in this
      review. Eight published case studies and case series were identified. Based on a
      limited body of evidence, dexmedetomidine shows promise as a potentially safe and
      possibly effective adjuvant treatment for AWS in the ICU. Prospective, well
      controlled studies are needed to confirm the safety and efficacy of the use of
      dexmedetomidine in AWS. 

PMID- 23975662
TI  - A meta-analysis on dose-response relationship between night shift work and the
      risk of breast cancer.
AB  - This study aimed to conduct a systematic review to sum up evidence of the
      associations between different aspects of night shift work and female breast
      cancer using a dose-response meta-analysis approach. We systematicly searched all
      cohort and case-control studies published in English on MEDLINE, Embase,
      PSYCInfo, APC Journal Club and Global Health, from January 1971 to May 2013. We
      extracted effect measures (relative risk, RR; odd ratio, OR; or hazard ratio, HR)
      from individual studies to generate pooled results using meta-analysis
      approaches. A log-linear dose-response regression model was used to evaluate the
      relationship between various indicators of exposure to night shift work and
      breast cancer risk. Downs and Black scale was applied to assess the
      methodological quality of included studies. Ten studies were included in the meta
      analysis. A pooled adjusted relative risk for the association between 'ever
      exposed to night shift work' and breast cancer was 1.19 [95% confidence interval
      (CI) 1.05-1.35]. Further meta-analyses on dose-response relationship showed that
      every 5-year increase of exposure to night shift work would correspondingly
      enhance the risk of breast cancer of the female by 3% (pooled RR = 1.03, 95% CI
      1.01-1.05; Pheterogeneity < 0.001). Our meta-analysis also suggested that an
      increase in 500-night shifts would result in a 13% (RR = 1.13, 95% CI 1.07-1.21;
      Pheterogeneity = 0.06) increase in breast cancer risk. This systematic review
      updated the evidence that a positive dose-response relationship is likely to
      present for breast cancer with increasing years of employment and cumulative
      shifts involved in the work. 

PMID- 23975663
TI  - A phase II randomized trial of induction chemotherapy versus no induction
      chemotherapy followed by preoperative chemoradiation in patients with esophageal
      cancer.
AB  - BACKGROUND: The contribution of induction chemotherapy (IC) before preoperative
      chemoradiation for esophageal cancer (EC) is not known. We hypothesized that IC
      would increase the rate of pathologic complete response (pathCR). METHODS:
      Trimodality-eligibile patients were randomized to receive no IC (Arm A) or IC
      (oxaliplatin/FU; Arm B) before oxaliplatin/FU/radiation. Surgery was attempted ~5
      6 weeks after chemoradiation. The pathCR rate, post-surgery 30-day mortality,
      overall survival (OS), and toxic effects were assessed. Bayesian methods and
      Fisher's exact test were used. RESULTS: One hundred twenty-six patients were
      randomized dynamically to balance the two arms for histology, baseline stage,
      gender, race, and age. Fifty-five patients in Arm A and 54 in Arm B underwent
      surgery. The median actuarial OS for all patients (54 deaths) was 45.62 months
      [95% confidence interval (CI), 27.63-NA], with median OS 45.62 months (95% CI
      25.56-NA) in Arm A and 43.68 months (95% CI 27.63-NA) in Arm B (P = 0.69). The
      pathCR rate in Arm A was 13% (7 of 55) and 26% (14 of 54) in Arm B (two-sided
      Fisher's exact test, P = 0.094). Safety was similar in both arms. CONCLUSIONS:
      These data suggest that IC produces non-significant increase in the pathCR rate
      and does not prolong OS. Further development of IC before chemoradiation may not
      be beneficial. Clinical trial no.: NCT 00525915 (www.clinicaltrials.gov).

PMID- 23975664
TI  - Prognostic role of microRNA polymorphisms in advanced gastric cancer: a
      translational study of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
AB  - BACKGROUND: To determine the prognostic role of selected microRNA (miRNA)
      polymorphisms in advanced gastric cancer (AGC). PATIENTS AND METHODS: Six hundred
      and seventy-four AGC patients received 5-fluorouracil (F), leucovorin (L),
      oxaliplatin (O) or FL + cisplatin (P) or additional docetaxel (T) to FLO (FLOT)
      within four clinical trials. Polymorphisms of mir-26a1 (rs7372209), mir-27a
      (rs895819), mir-100 (rs1834306), mir-146a (rs2910164), mir-196-a2 (rs11614913),
      mir-219-1 (rs107822) and mir-423 (rs6505162) were genotyped. Variable selection
      for the final multivariate model (n = 487) was based on univariate and
      multivariate Cox-regression analyses with a cut-off P-value of <= 20%. RESULTS:
      Genetic factors significantly associated with overall survival (OS) were
      rs7372209 (mir-26a1) variant genotypes (hazard ratio, HR 1.307 [95% confidence
      interval (CI) 1.031-1.656], P = 0.0272), rs895819 (mir-27a) variant genotypes (HR
      1.304 [95% CI 1.031-1.650], P = 0.0270) and rs11614913 (mir-196a2) variant
      genotypes (HR 0.791 [95% CI 0.625-1.000], P = 0.0497). Clinical factors with
      significant impact on OS were Eastern Cooperative Oncology Group (ECOG) 2
      performance status (HR 1.880 [95% CI 1.254-2.820], P = 0.0023), curative surgery
      of advanced disease (HR 0.235 [95% CI 0.123-0.449], P < 0.0001) and addition of
      docetaxel in locally AGC patients (HR 0.348 [95% CI 0.145-0.838], P = 0.0301).
      Combined analyses revealed an improved OS in patients without any unfavourable
      genotype of 18 months compared with 14, 12 and 10 months in patients with 1, 2
      and 3 unfavourable genotypes, respectively (P = 0.0257). CONCLUSIONS: These data
      suggest a significant impact of selected miRNA polymorphisms on prognosis in AGC.

PMID- 23975665
TI  - Combination of gemcitabine and cetuximab in patients with advanced
      cholangiocarcinoma: a phase II study of the Belgian Group of Digestive Oncology.
AB  - BACKGROUND: Cholangiocarcinomas are uncommon tumours with a poor prognosis, that
      frequently present epidermal growth factor receptor overexpression. METHODS: In a
      multi-centre phase II trial, patients with unresectable cholangiocarcinoma, naive
      to chemotherapy, received Cetuximab (400 mg/m(2) at week 1, then 250
      mg/m(2)/week) and Gemcitabine (1 g/m(2) on day 1, 8 and 15 every 4 weeks).
      Primary end point was progression-free survival (PFS) rate at 6 months, using a
      Simon 2-stage design. Moreover, we assessed the impact of KRAS status and skin
      toxic effect on efficacy. RESULTS: Forty-four patients (41% locally advanced/59%
      metastatic) were enrolled. Median age was 61.5 years; ECOG PS was 0 (68%) or 1.
      Six months PFS reached 47%. Median OS was 13.5 months [95% confidence interval
      (CI) 9.8-31.8 months]. Nine patients (20.4%) had PR and disease-control rate was
      79.5%. Grade 3/4-related toxic effects were haematological (52.2%), skin rash
      (13.6%) and fatigue (11.4%). KRAS mutations were found in 7 of 27 patients and
      had no influence on PFS. Skin toxic effect >=grade 2 was associated with
      increased PFS (P = 0.05). CONCLUSION(S): Our study met its primary end point,
      suggesting that Gemcitabine-Cetuximab has activity in cholangiocarcinoma. KRAS
      status was not associated with PFS, unlike skin toxic effect, which could be used
      as a surrogate marker for efficacy. ClinicalTrials.gov Identifier: NCT00747097.

PMID- 23975666
TI  - Penile cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and
      follow-up.

PMID- 23975667
TI  - DCE-CT in the follow-up of targeted therapy in GISTs.

PMID- 23975668
TI  - Clinical outcomes of endovascular treatments for critical limb ischemia with
      chronic total occlusive lesions limited to below-the-knee arteries.
AB  - BACKGROUND: Diabetes mellitus tends to have the greatest impact on the smaller
      vessels and contributes significantly to occlusive disease from the popliteal
      artery distally. PURPOSE: To evaluate the clinical outcomes after a balloon
      angioplasty with or without stent placement in diabetic patients with critical
      limb ischemia (CLI) by chronic total occlusion (CTO) limited to below-the-knee
      (BTK) arteries. MATERIAL AND METHODS: From August 2005, patients who presented
      CLI and CTO limited to the BTK arteries, and who underwent endovascular
      treatment, were included in this study. The primary endpoints evaluated were
      technical success, limb salvage, and primary patency. The secondary endpoints
      evaluated were 30-day access site, intervention site, and systemic complications.
      Patency and limb salvage were evaluated using the Kaplan-Meier method and
      compared using Fisher's exact test. RESULTS: The BTK endovascular treatment (EVT)
      was performed on 64 limbs. Technical success rate was 93.8% and limb salvage rate
      was 90.6%. Three of four limbs with technical failure and three of 60 limbs with
      technical success underwent BTK amputation and the comparison of these rates were
      significantly different (75% vs. 5%, P = 0.002). Primary patency rates for the
      limbs were 75% and 59.1% at 6-month and 12-month follow-up, respectively. Minor
      complications disappeared through the follow-up periods and there was no 30-day
      complication or systemic adverse events for the treated vessel. CONCLUSION: Even
      though EVT for CLI in patients with diabetes and CTO in isolated BTK arteries
      does not have comparable primary patency, it can lead to a very high rate of limb
      salvage. This result can accentuate the importance of more blood flow to the foot
      by means of successful revascularization using EVT rather than long-term patency
      in CTO of isolated BTK arteries.

PMID- 23975669
TI  - Clinical findings related to intramammary infections in meat-producing ewes.
AB  - The aim of this study was to investigate the relationship between clinical
      findings and bacterial isolation in milk samples of meat-producing ewes. The
      study was conducted in 17 commercial flocks and 550 udder halves from suckling
      Santa Ines ewes. Initially, the clinical examination of the mammary glands and
      teats was performed by visual inspection and palpation of the teats and udder
      halves; then a scoring system was devised for all the findings. After that, the
      strip cup test and the California mastitis test (CMT) were performed. Then, milk
      samples for somatic cell counts (SCCs) and bacteriological analyses were
      collected. Staphylococci bacteria were the main etiological agent isolated in the
      present study. Upon investigation of the correlations between bacterial isolation
      and the clinical findings, only the presence of teat injury, pendulous udder, and
      alterations in the palpation of the teat were associated with bacterial
      isolation. A significant correlation between bacteriologically positive milk
      samples and CMT and SCC was also found. Thus, some clinical findings appeared as
      a risk factor for bacteriologically positive milk samples and can be used as a
      tool in mastitis control programs. However, a complete and extensive diagnosis,
      an appropriate therapy, and an efficient mastitis control program will require
      the combination of clinical examination, microbiological tests, and SCC. 

PMID- 23975670
TI  - Dynamical behaviour of a two-predator model with prey refuge.
AB  - A three-component model consisting on one-prey and two-predator populations is
      considered with a Holling type II response function incorporating a constant
      proportion of prey refuge. We also consider the competition among predators for
      their food (prey) and shelter. The essential mathematical features of the model
      have been analyzed thoroughly in terms of stability and bifurcations arising in
      some selected situations. Threshold values for some parameters indicating the
      feasibility and stability conditions of some equilibria are determined. The range
      of significant parameters under which the system admits different types of
      bifurcations is investigated. Numerical illustrations are performed in order to
      validate the applicability of the model under consideration. 

PMID- 23975671
TI  - Modeling the impact of early therapy for latent tuberculosis patients and its
      optimal control analysis.
AB  - Effective tuberculosis (TB) control depends on case findings to discover
      infectious cases, investigation of contacts of those with TB, as well as
      appropriate treatment. Adherence and successful completion of the treatment are
      equally important. Unfortunately, due to a number of personal, psychosocial,
      economic, medical, and health service factors, a significant number of TB
      patients become irregular and default from treatment. In this paper, a
      mathematical model is developed to assess the impact of early therapy for latent
      TB and non-adherence on controlling TB transmission dynamics. Equilibrium states
      of the model are determined and their local stability is examined. With the aid
      of the center manifold theory, it is established that the model undergoes a
      backward bifurcation. Qualitative mathematical analysis of the model suggests
      that a high level of latent tuberculosis case findings, coupled with a decrease
      of defaulting rate, may be effective in controlling TB transmission dynamics in
      the community. Population-level effects of organized campaigns to improve early
      therapy and to guarantee successful completion of each treatment are evaluated
      through numerical simulations and presented in support of the analytical results.

PMID- 23975672
TI  - Changes of protein stiffness during folding detect protein folding intermediates.
AB  - Single-molecule force-quench atomic force microscopy (FQ-AFM) is used to detect
      folding intermediates of a simple protein by detecting changes of molecular
      stiffness of the protein during its folding process. Those stiffness changes are
      obtained from shape and peaks of an autocorrelation of fluctuations in end-to-end
      length of the folding molecule. The results are supported by predictions of the
      equipartition theorem and agree with existing Langevin dynamics simulations of a
      simplified model of a protein folding. In the light of the Langevin simulations
      the experimental data probe an ensemble of random-coiled collapsed states of the
      protein, which are present both in the force-quench and thermal-quench folding
      pathways. 

PMID- 23975673
TI  - The diversity and antimicrobial activity of Preussia sp. endophytes isolated from
      Australian dry rainforests.
AB  - Limited knowledge currently exists regarding species diversity and antimicrobial
      activity of endophytic isolates of Preussia within Australia. This report
      describes endophytic Preussia species that were identified through molecular
      analysis of the internal transcribed spacer region. Screening for antimicrobial
      secondary metabolites was determined by testing crude ethyl acetate (EtOAc)
      extracts derived from fungal mycelia against a panel of ATCC type strains which
      included Bacillus cereus, Escherichia coli, Enterococcus faecalis, Pseudomonas
      aeruginosa, Serratia marcescens, methicillin-resistant Staphylococcus aureus
      (MRSA) and the opportunist yeast pathogen Candida albicans. Subsequently, high
      performance liquid chromatography generated fractions of bioactive EtOAc extracts
      which were subject to confirmatory testing using the Clinical and Laboratory
      Standards Institute reference microdilution antimicrobial activity assay. A total
      of 18 Preussia were isolated from nine host plants with 6/18 having a <97 %
      sequence similarity to other known species in Genbank, suggesting that they are
      new species. In preliminary screening, 13/18 Preussia isolates revealed
      antimicrobial activity against at least one of the microbes tested, whilst 6/18
      isolates, including 4/6 putative new species showed specific antimicrobial
      activity against MRSA and C. albicans. These results highlight the antimicrobial
      potential of Australian Preussia spp. and also the importance of Australian dry
      rainforests as an untapped repository of potentially significant bioactive
      compounds. 

PMID- 23975674
TI  - Non-pharmacological interventions for fatigue in rheumatoid arthritis.
AB  - BACKGROUND: Fatigue is a common and potentially distressing symptom for people
      with rheumatoid arthritis with no accepted evidence based management guidelines.
      Non-pharmacological interventions, such as physical activity and psychosocial
      interventions, have been shown to help people with a range of other long-term
      conditions to manage subjective fatigue. OBJECTIVES: To evaluate the benefit and
      harm of non-pharmacological interventions for the management of fatigue in people
      with rheumatoid arthritis. This included any intervention that was not classified
      as pharmacological in accordance with European Union (EU) Directive 2001/83/EEC.
      SEARCH METHODS: The following electronic databases were searched up to October
      2012, Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE;
      AMED; CINAHL; PsycINFO; Social Science Citation Index; Web of Science;
      Dissertation Abstracts International; Current Controlled Trials Register; The
      National Research Register Archive; The UKCRN Portfolio Database. In addition,
      reference lists of articles identified for inclusion were checked for additional
      studies and key authors were contacted. SELECTION CRITERIA: Randomised controlled
      trials were included if they evaluated a non-pharmacological intervention in
      people with rheumatoid arthritis with self-reported fatigue as an outcome
      measure. DATA COLLECTION AND ANALYSIS: Two review authors selected relevant
      trials, assessed risk of bias and extracted data. Where appropriate, data were
      pooled using meta-analysis with a random-effects model. MAIN RESULTS: Twenty-four
      studies met the inclusion criteria, with a total of 2882 participants with
      rheumatoid arthritis. Included studies investigated physical activity
      interventions (n = 6 studies; 388 participants), psychosocial interventions (n =
      13 studies; 1579 participants), herbal medicine (n = 1 study; 58 participants),
      omega-3 fatty acid supplementation (n = 1 study; 81 participants), Mediterranean
      diet (n = 1 study; 51 participants), reflexology (n = 1 study; 11 participants)
      and the provision of Health Tracker information (n = 1 study; 714 participants).
      Physical activity was statistically significantly more effective than the control
      at the end of the intervention period (standardized mean difference (SMD) -0.36,
      95% confidence interval (CI) -0.62 to -0.10; back translated to mean difference
      of 14.4 points lower, 95% CI -4.0 to -24.8 on a 100 point scale where a lower
      score means less fatigue; number needed to treat for an additional beneficial
      outcome (NNTB) 7, 95% CI 4 to 26) demonstrating a small beneficial effect upon
      fatigue. Psychosocial intervention was statistically significantly more effective
      than the control at the end of the intervention period (SMD -0.24, 95% CI -0.40
      to -0.07; back translated to mean difference of 9.6 points lower, 95% CI -2.8 to 
      16.0 on a 100 point scale, lower score means less fatigue; NNTB 10, 95% CI 6 to
      33) demonstrating a small beneficial effect upon fatigue. For the remaining
      interventions meta-analysis was not possible and there was either no
      statistically significant difference between trial arms or findings were not
      reported. Only three studies reported any adverse events and none of these were
      serious, however, it is possible that the low incidence was in part due to poor
      reporting. The quality of the evidence ranged from moderate quality for physical
      activity interventions and Mediterranean diet to low quality for psychosocial
      interventions and all other interventions. AUTHORS' CONCLUSIONS: This review
      provides some evidence that physical activity and psychosocial interventions
      provide benefit in relation to self-reported fatigue in adults with rheumatoid
      arthritis. There is currently insufficient evidence of the effectiveness of other
      non-pharmacological interventions.

PMID- 23975675
TI  - Bombarding cancer: biolistic delivery of therapeutics using porous Si carriers.
AB  - A new paradigm for an effective delivery of therapeutics into cancer cells is
      presented. Degradable porous silicon carriers, which are tailored to carry and
      release a model anti-cancer drug, are biolistically bombarded into in-vitro
      cancerous targets. We demonstrate the ability to launch these highly porous
      microparticles by a pneumatic capillary gene gun, which is conventionally used to
      deliver cargos by heavy metal carriers. By optimizing the gun parameters e.g.,
      the accelerating gas pressure, we have successfully delivered the porous
      carriers, to reach deep targets and to cross a skin barrier in a highly spatial
      resolution. Our study reveals significant cytotoxicity towards the target human
      breast carcinoma cells following the delivery of drug-loaded carriers, while
      administrating empty particles results in no effect on cell viability. The unique
      combination of biolistics with the temporal control of payload release from
      porous carriers presents a powerful and non-conventional platform for designing
      new therapeutic strategies. 

PMID- 23975676
TI  - Metabolic evaluation of patients with urinary system stone disease: a research of
      pediatric and adult patients.
AB  - OBJECTIVES: To determine the metabolic risk factors in children and adults with
      urinary system stone disease. MATERIALS AND METHODS: Between September 2008 and
      February 2011, 257 patients who underwent 24-h urine analysis because of urinary
      system stone disease were included in the present study. Group I and II include
      only adult patients. The first-time stone formers were named as Group I (n =
      106), and recurrent stone formers were named as Group II (n = 107). Group III was
      occurred by pediatric patients (n = 44). Control group includes 105 people was
      called as Group IV. This group was divided into two subgroups. Group IVa includes
      70 adult people, and Group IVb includes 35 children. The metabolic evaluation
      results of patients and control groups were compared. RESULTS: Hypercalciuria
      (35.8, 44.9, and 47.7 % for Group I, II, and III, respectively) and
      hypocitraturia (42.5, 40.2, and 50 % for Group I, II, and III, respectively) were
      most common risk factors for stone formation. However, unlike the literature, we
      have seen that hypomagnesiuria is also an important risk factor in adults and
      children. Hypomagnesiuria was defined at 36.4 % in Group I, 29 % in Group II, and
      56.8 % in Group III (p < 0.05 for each group). These three parameters were
      significantly different between patient and control groups. CONCLUSIONS:
      Hypomagnesiuria, hypocitraturia, and hypercalciuria are the most important risk
      factors for stone formation in adults and pediatric patients.

PMID- 23975677
TI  - Management of double-refractory multiple myeloma.
AB  - Widespread use of the novel agents bortezomib and lenalidomide has improved
      outcomes in multiple myeloma (MM). Despite remarkable progress, patients will
      eventually relapse after exhausting treatment with these drugs. Management of
      myeloma that is refractory to both bortezomib and lenalidomide (double-refractory
      MM, DRMM) is complicated due to disease, patient, and treatment-related factors
      and new therapies for these patients are required. A review of the unique
      challenges of treating DRMM, recently FDA-approved therapeutic agents, and
      selected novel drugs under active clinical investigation, is presented below.

PMID- 23975678
TI  - New approaches to smoldering myeloma.
AB  - Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder
      characterized by the presence of one or both features of serum M-protein >= 30
      g/L and bone marrow plasma cell infiltration >= 10 %. However, myeloma-related
      symptomatology is absent from this condition. The risk of progression to active
      MM is not uniform, and several markers are useful for identifying SMM patients at
      high risk of progression to active MM. These include the size of the M-protein
      and the infiltration in the bone marrow, the serum-free light-chain ratio, the
      presence of immunoparesis and percentage of plasma cell with aberrant phenotype
      by flow cytometry, or the presence of focal lesions in magnetic resonance
      imaging. Overall, the presence of these factors identifies patients who have a 50
      % probability of progression at 2 years, and the forthcoming challenge will be to
      identify ultra-high-risk patients who have an 80 % risk of progression at 2
      years. The current standard of care is not to treat until progression to
      symptomatic disease occurs. Several trials of melphalan, thalidomide and
      bisphosphonates have been conducted in the overall SMM patient population to
      examine the delay in time to progression (TTP) to symptomatic disease, but these
      have shown no significant benefit. However, a randomized trial that focused on
      high-risk SMM patients allocated to receive early treatment with lenalidomide
      plus dexamethasone versus observation did report a significant benefit with
      respect to TTP and overall survival. In summary, high-risk SMM patients should be
      targetted for early treatment, and more so efforts should be made to identify the
      ultra-high-risk subgroup within the high-risk SMM patient population which may be
      considered as early MM and thereby candidates for receiving therapy before they
      develop myeloma-related symptomatology.

PMID- 23975679
TI  - Loss of FHL1 induces an age-dependent skeletal muscle myopathy associated with
      myofibrillar and intermyofibrillar disorganization in mice.
AB  - Recent human genetic studies have provided evidences that sporadic or inherited
      missense mutations in four-and-a-half LIM domain protein 1 (FHL1), resulting in
      alterations in FHL1 protein expression, are associated with rare congenital
      myopathies, including reducing body myopathy and Emery-Dreifuss muscular
      dystrophy. However, it remains to be clarified whether mutations in FHL1 cause
      skeletal muscle remodeling owing to gain- or loss of FHL1 function. In this
      study, we used FHL1-null mice lacking global FHL1 expression to evaluate loss-of
      function effects on skeletal muscle homeostasis. Histological and functional
      analyses of soleus, tibialis anterior and sternohyoideus muscles demonstrated
      that FHL1-null mice develop an age-dependent myopathy associated with
      myofibrillar and intermyofibrillar (mitochondrial and sarcoplasmic reticulum)
      disorganization, impaired muscle oxidative capacity and increased autophagic
      activity. A longitudinal study established decreased survival rates in FHL1-null
      mice, associated with age-dependent impairment of muscle contractile function and
      a significantly lower exercise capacity. Analysis of primary myoblasts isolated
      from FHL1-null muscles demonstrated early muscle fiber differentiation and
      maturation defects, which could be rescued by re-expression of the FHL1A isoform,
      highlighting that FHL1A is necessary for proper muscle fiber differentiation and
      maturation in vitro. Overall, our data show that loss of FHL1 function leads to
      myopathy in vivo and suggest that loss of function of FHL1 may be one of the
      mechanisms underlying muscle dystrophy in patients with FHL1 mutations. 

PMID- 23975680
TI  - Modulation of lipid metabolic defects rescues cleft palate in Tgfbr2 mutant mice.
AB  - Mutations in transforming growth factor beta (TGFbeta) receptor type II (TGFBR2)
      cause Loeys-Dietz syndrome, characterized by craniofacial and cardiovascular
      abnormalities. Mice with a deletion of Tgfbr2 in cranial neural crest cells
      (Tgfbr2(fl/fl);Wnt1-Cre mice) develop cleft palate as the result of abnormal
      TGFbeta signaling activation. However, little is known about metabolic processes
      downstream of TGFbeta signaling during palatogenesis. Here, we show that Tgfbr2
      mutant palatal mesenchymal cells spontaneously accumulate lipid droplets,
      resulting from reduced lipolysis activity. Tgfbr2 mutant palatal mesenchymal
      cells failed to respond to the cell proliferation stimulator sonic hedgehog,
      derived from the palatal epithelium. Treatment with p38 mitogen-activated protein
      kinase (MAPK) inhibitor or telmisartan, a modulator of p38 MAPK activation and
      lipid metabolism, blocked abnormal TGFbeta-mediated p38 MAPK activation,
      restoring lipid metabolism and cell proliferation activity both in vitro and in
      vivo. Our results highlight the influence of alternative TGFbeta signaling on
      lipid metabolic activities, as well as how lipid metabolic defects can affect
      cell proliferation and adversely impact palatogenesis. This discovery has broader
      implications for the understanding of metabolic defects and potential prevention
      of congenital birth defects. 

PMID- 23975682
TI  - Herbal medicines for fatty liver diseases.
AB  - BACKGROUND: Fatty liver disease is potentially a reversible condition that may
      lead to end-stage liver disease. Since herbal medicines such as Crataegus
      pinnatifida and Salvia miltiorrhiza have increasingly been used in the management
      of fatty liver disease, a systematic review on herbal medicine for fatty liver
      disease is needed. OBJECTIVES: To assess the beneficial and harmful effects of
      herbal medicines for people with alcoholic or non-alcoholic fatty liver disease.
      SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3,
      2012), MEDLINE, EMBASE, and Science Citation Index Expanded to 1 March 2012. We
      also searched the Chinese BioMedical Database, Traditional Chinese Medical
      Literature Analysis and Retrieval System, China National Knowledge
      Infrastructure, Chinese VIP Information, Chinese Academic Conference Papers
      Database and Chinese Dissertation Database, and the Allied and Complementary
      Medicine Database to 2 March 2012. SELECTION CRITERIA: We included randomised
      clinical trials comparing herbal medicines with placebo, no treatment, a
      pharmacological intervention, or a non-pharmacological intervention such as diet
      or lifestyle, or Western interventions in participants with fatty liver disease.
      DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently. We
      used the 'risk of bias' tool to assess the risk of bias of the included trials.
      We assessed the following domains: random sequence generation, allocation
      concealment, blinding, incomplete outcome data, selective outcome reporting, and
      other sources of bias. We presented the effects estimates as risk ratios (RR)
      with 95% confidence intervals (CI) or as mean differences (MD) with 95% CI,
      depending on the variables of the outcome measures. MAIN RESULTS: We included 77
      randomised clinical trials, which included 6753 participants with fatty liver
      disease. The risks of bias (overestimation of benefits and underestimation of
      harms) was high in all trials. The mean sample size was 88 participants (ranging
      from 40 to 200 participants) per trial. Seventy-five different herbal medicine
      products were tested. Herbal medicines tested in the randomised trials included
      single-herb products (Gynostemma pentaphyllum, Panax notoginseng, and Prunus
      armeniaca), proprietary herbal medicines commercially available, and combination
      formulas prescribed by practitioners. The most commonly used herbs were Crataegus
      pinnatifida,Salvia miltiorrhiza,Alisma orientalis,Bupleurum Chinense,Cassia
      obtusifolia, Astragalus membranaceous, and Rheum palmatum. None of the trials
      reported death, hepatic-related morbidity, quality of life, or costs. A large
      number of trials reported positive effects on putative surrogate outcomes such as
      serum aspartate aminotransferase, alanine aminotransferase, glutamyltransferase,
      alkaline phosphatases, ultrasound, and computed tomography scan. Twenty-seven
      trials reported adverse effects and found no significant difference between
      herbal medicines versus control. However, the risk of bias of the included trials
      was high.The outcomes were ultrasound findings in 22 trials, liver computed
      tomography findings in eight trials, aspartate aminotransferase levels in 64
      trials, alanine aminotransferase activity in 77 trials, and glutamyltransferase
      activities in 44 trials. Six herbal medicines showed statistically significant
      beneficial effects on ultrasound, four on liver computed tomography, 42 on
      aspartate aminotransferase activity, 49 on alanine aminotransferase activity,
      three on alkaline phosphatases activity, and 32 on glutamyltransferase activity
      compared with control interventions. AUTHORS' CONCLUSIONS: Some herbal medicines
      seemed to have positive effects on aspartate aminotransferase, alanine
      aminotransferase, ultrasound, and computed tomography. We found no significant
      difference on adverse effects between herbal medicine and control groups. The
      findings are not conclusive due to the high risk of bias of the included trials
      and the limited number of trials testing individual herbal medicines.
      Accordingly, there is also high risk of random errors.

PMID- 23975683
TI  - Brand.

PMID- 23975681
TI  - A model for the molecular underpinnings of tooth defects in Axenfeld-Rieger
      syndrome.
AB  - Patients with Axenfeld-Rieger Syndrome (ARS) present various dental
      abnormalities, including hypodontia, and enamel hypoplasia. ARS is genetically
      associated with mutations in the PITX2 gene, which encodes one of the earliest
      transcription factors to initiate tooth development. Thus, Pitx2 has long been
      considered as an upstream regulator of the transcriptional hierarchy in early
      tooth development. However, because Pitx2 is also a major regulator of later
      stages of tooth development, especially during amelogenesis, it is unclear how
      mutant forms cause ARS dental anomalies. In this report, we outline the
      transcriptional mechanism that is defective in ARS. We demonstrate that during
      normal tooth development Pitx2 activates Amelogenin (Amel) expression, whose
      product is required for enamel formation, and that this regulation is perturbed
      by missense PITX2 mutations found in ARS patients. We further show that Pitx2
      mediated Amel activation is controlled by chromatin-associated factor Hmgn2, and
      that Hmgn2 prevents Pitx2 from efficiently binding to and activating the Amel
      promoter. Consistent with a physiological significance to this interaction, we
      show that K14-Hmgn2 transgenic mice display a severe loss of Amel expression on
      the labial side of the lower incisors, as well as enamel hypoplasia-consistent
      with the human ARS phenotype. Collectively, these findings define transcriptional
      mechanisms involved in normal tooth development and shed light on the molecular
      underpinnings of the enamel defect observed in ARS patients who carry PITX2
      mutations. Moreover, our findings validate the etiology of the enamel defect in a
      novel mouse model of ARS. 

PMID- 23975684
TI  - Identifying predictors of hospice eligibility in patients with Parkinson disease.
AB  - This study aims to improve recognition of hospice eligibility for patients with
      Parkinson disease (PD) by ascertaining which variables have a higher probability
      of occurring uniquely in 6 to 12 months before death when compared to 18 to 24
      months before death. Participants were 339 patients who died who were diagnosed
      with PD or Parkinsonism and treated with dopaminergic prescriptions for at least
      3 years in northwestern US Veterans Affairs medical centers. A range of
      indicators were compared across 3 time periods (30-36 months, 24-18 months, and
      12-6 months before death) using within-subjects repeated measures design. Results
      indicate that body mass index less than 18, alone or combined with a shift in
      prescribing (when benefits of dopaminergic medications no longer outweigh their
      risk of side effects), may signal appropriate timing for hospice referral. 

PMID- 23975685
TI  - Generation of porcine induced pluripotent stem cells and evaluation of their
      major histocompatibility complex protein expression in vitro.
AB  - Induced pluripotent stem cells (iPSCs) are thought to be highly beneficial in the
      field of regenerative medicine and are believed to overcome immunogenic barriers
      to cell transplantation. However, issues remain regarding their safety and
      efficiency for medical use. Furthermore, some recent reports have suggested that
      iPSCs could be targeted by the autologous immune system. To promote practical
      applications of iPSCs, in depth research using appropriate animal models is
      needed and porcine species appear to provide an ideal model. Recent studies have
      focused on the generation of porcine iPSC cells, but no investigations of their
      immunological properties have been conducted to date. In the present study, we
      generated putative iPSCs from porcine somatic cells and measured major
      histocompatibility complex (MHC) expression on the iPSCs and their derivatives.
      Compact colonies that expressed pluripotent markers appeared 11 days after viral
      infection. Embryonic bodies (EB) were produced and differentiated into three germ
      layers in vitro. Karyotyping and swine leukocyte antigen (SLA) typing showed that
      the iPSCs were identical to parental somatic cells. Porcine iPSCs expressed only
      low levels of MHC class I and moderately increased levels on their differentiated
      derivatives, whereas MHC class II was rarely expressed. In the presence of
      interferon-gamma (IFN-gamma), the expression of MHC class I was elevated on
      differentiated iPSCs, and gradually decreased after withdrawal of the cytokine.
      Our data suggest that porcine iPSCs could be useful for preclinical studies of
      the efficiency and viability of iPSCs, and for devising strategies to rescue
      transplanted cells from the autologous immune system.

PMID- 23975686
TI  - Biomarkers in sepsis.
AB  - There is much enthusiasm and interest in sepsis biomarkers, particularly because
      sepsis is a highly lethal condition, its diagnosis is challenging, and even
      simple treatment with antibiotics has led to serious adverse consequences such as
      emergence of resistant pathogens. Yet development of a sepsis biomarker requires
      many more steps than simply finding an association between a particular molecule
      and a clinical state or outcome. Demonstration of improvement of therapeutic
      practice using receiver-operating characteristic and other analyses is important.
      Validation in independent, prospective and, preferably, multicenter trials is
      essential. Many promising candidate sepsis biomarkers have recently been
      proposed. While procalcitonin (PCT) is currently the most studied sepsis
      biomarker, evidence of potential value has been found for a wide array of blood
      biomarkers including proteins, mRNA expression in whole blood or leukocytes,
      micro-RNAs (miRNA), pathogen and host DNA, pathogen and host genetic variants and
      metabolomic panels, and even in the novel use of currently available clinical
      data. While the most common early reports link putative sepsis biomarker levels
      to severity of illness and outcome (prognostic), this is not anticipated to be
      their primary use. More important is the distinction between infection and
      noninfectious inflammatory responses (diagnostic) and the use of sepsis
      biomarkers to direct therapy (predictive). 

PMID- 23975687
TI  - Determinants of hospital mortality among patients with sepsis or septic shock
      receiving appropriate antibiotic treatment.
AB  - Septic shock affects 750,000 people annually, and accounts for 10 % of all deaths
      annually in the US. In recent years, outcomes in patients with septic shock have
      improved; however, mortality still remains high at 40 - 50 %. The use of early
      protocolized resuscitation goals have been associated with reduced mortality in
      septic shock. However, strong evidenced-based recommendations for the continued
      management of patients with septic shock in the ICU setting are currently
      lacking. Appropriate antibiotic therapy is the cornerstone of management in
      septic shock. Inappropriate antibiotic therapy can lead to treatment failures and
      adverse outcomes, including high risk of mortality. This article outlines other
      key factors that contribute to outcome in septic shock. It is challenging for
      physicians to optimize therapy when fixed patient features such as age and
      underlying comorbidity can negatively influence mortality. However, outcomes can
      also potentially be affected by physician management decisions including fluid
      balance, corticosteroid use, glucose control and adherence to protocols including
      early goal-directed therapy and infection-control measures. Certain pathogen
      virulence characteristics also adversely affect outcomes. We give an overview of
      the determinants of outcome in septic shock in the setting of appropriate
      antibiotic use. 

PMID- 23975688
TI  - Noncanonical Nuclear Factor Kappa B (NF-kappaB) Signaling and Potential for
      Therapeutics in Sepsis.
AB  - NF-kappaB signaling plays a central role in the pathophysiology of severe sepsis
      and septic shock. Despite tremendous and missed efforts, novel therapeutics for
      severe sepsis and septic shock are still needed. Many drugs have been designed to
      target the canonical NF-kappaB signaling pathway with limited success,
      potentially due to the nonspecificity of the drugs for other kinases and the
      interaction of canonical signaling with other pathways. Here, we review the
      canonical and noncanonical signaling pathways of NF-kappaB, the cross talk and
      negative regulation of the two pathways, and the potential for therapeutics
      arising from the noncanonical NF-kappaB pathway in relation to the
      pathophysiology of septic shock. 

PMID- 23975689
TI  - Non invasive assessment of lung disease in ataxia telangiectasia by high-field
      magnetic resonance imaging.
AB  - PURPOSE: A sensitive imaging technique that assesses ataxia telangiectasia (AT)
      lung disease without ionizing radiation is highly desirable. We designed a study
      to evaluate lung changes using magnetic resonance imaging (MRI), and to
      investigate the relationships among severity and extent of pulmonary
      abnormalities and clinical, microbiological and functional data in children and
      young adults with AT. METHODS: Fifteen AT patients (age, 11.3 years; range, 6-31)
      underwent 3.0-T MRI, spirometry, and deep throat or sputum culture. Images were
      scored using a modified Helbich score. RESULTS: Although only 8 patients (53 %)
      had recurrent/chronic respiratory symptoms, MRI identified lung abnormalities in
      all. Bronchiectasis, peribronchial thickening, mucous plugging, and
      collapse/consolidation were present in 60 %, 87 %, 67 %, and 13 % of cases,
      respectively, with no difference between subjects with or without respiratory
      symptoms. No difference in changes of specific scores was found between the two
      groups, but the total MRI score was higher in patients with respiratory symptoms
      (6.5 versus 5, respectively; p = 0.02). Total or specific MRI scores were not
      associated with patients' age. Of all scores, only mucous plugging subscore
      appeared significantly related to FEV1 (r = 0.7, p = 0.04) and FEF25-75% (r =
      0.9, p = 0.001). MRI scores from patients with positive (n = 5) or negative (n =
      10) sputum culture were not significantly different. CONCLUSIONS: MRI is valuable
      in the assessment of extent and severity of pulmonary changes in children and
      adults with AT. It represents an helpful tool for the longitudinal evaluation of
      patients and may be also used as an outcome surrogate to track the effects of
      medications.

PMID- 23975690
TI  - Complete genome sequences of three rabies viruses isolated from rabid raccoon
      dogs and a cow in Korea.
AB  - The complete genomes of three rabies viruses (BD0406CC, BV9901PJ, and 08F40) of
      two raccoon dogs (Nyctereutes procyonoides koreensis) and a cow were determined.
      The genomic organization is typical of rabies viruses, and the open reading
      frames of the N, P, M, G, and L genes are 1,353, 894, 609, 1,575, and 6,384 bases
      in length, respectively. The full genome length of the three strains was 11,928
      nucleotides, and the sequence similarity between the rabies viruses at the
      nucleotide level was 98.5-99.5%. Sequence comparisons indicated that these rabies
      viruses belong to the "Arctic and Arctic-like" group, with high homology to the
      Eurasian cluster. All Korean strains were clustered with the Mongolia strains,
      which belong to Arctic-like 1 clade. The 08F40 and BD0406CC strains were
      constructed with rabies virus strains isolated in Gangwon province. The BV9901PJ
      strain was closely related to strains isolated in Gyeonggi province in Korea.
      Three strains were more dependent upon geographical distribution and time period
      than host species. Complete genome sequencing of different host-origin rabies
      viruses will provide information that should contribute to understanding the
      transmission cycle and genetic variability of rabies from different hosts.

PMID- 23975691
TI  - LNG-IUS versus oral progestogen treatment for endometrial hyperplasia: a long
      term comparative cohort study.
AB  - STUDY QUESTION: What are the regression and hysterectomy rates for women treated
      with the levonorgestrel-releasing intrauterine system (LNG-IUS) compared with
      oral progestogens for endometrial hyperplasia (EH)? SUMMARY ANSWER: The LNG-IUS
      achieves higher regression and lower hysterectomy rates than oral progestogens in
      the treatment of complex and atypical hyperplasia. WHAT IS KNOWN ALREADY: The LNG
      IUS and oral progestogens are both equally used to treat women with EH. There is
      uncertainty about whether the LNG-IUS is a better therapy for EH. STUDY DESIGN,
      SIZE, DURATION: This comparative cohort study included 344 women recruited from
      August 1998 until December 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women
      with complex non-atypical or atypical EH were treated with the LNG-IUS (n = 250)
      or oral progestogens (n = 94) in a tertiary referral hospital. We evaluated the
      proportion of women who regressed or underwent hysterectomy after treatment with
      the LNG-IUS compared with oral progestogens by logistic regression adjusting for
      confounding. The time from diagnosis to regression was explored through a
      survival analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The follow-up rate was
      95.3%. The mean length of follow-up in the two groups was 66.9 +/- SD 35.1 months
      for the LNG-IUS and 87.2 +/- SD 45.5 months for the oral progestogen group.
      Regression of hyperplasia was achieved in 94.8% (237/250) of patients with the
      LNG-IUS compared with 84.0% (79/94) of patients treated with oral progestogens
      (adjusted odds ratio (OR) = 3.04, 95% CI 1.36-6.79, P = 0.001). Hysterectomy
      rates were lower in the LNG-IUS group during follow-up (22.1, 55/250 versus
      37.2%, 35/94, adjusted OR = 0.48, 95% CI 0.28-0.81, P < 0.004). Endometrial
      cancer was diagnosed in 8 (33%) women who had hysterectomy because of a failure
      to regress to normal histology during follow-up (n = 24). LIMITATIONS, REASONS
      FOR CAUTION: The observational design cannot exclude residual confounding from
      unmeasured variables. WIDER IMPLICATIONS OF THE FINDINGS: In treating EH, LNG-IUS
      achieves higher regression rates and lower hysterectomy rates than oral
      progestogens and should be the first-line therapy. Failure to achieve regression
      carries a high risk of underlying endometrial cancer and hysterectomy is advised.

PMID- 23975692
TI  - Aerobic decolorization of Acid Brilliant Scarlet GR by microbial community and
      the community dynamics during sequencing batch processes.
AB  - In this research, aerobic decolorization of Acid Brilliant Scarlet GR by
      microbial community was studied. Effects of conditions and dye concentraion on
      decolorization processes were investigated. Additionally, continuous
      decolorization was evaluated through sequencing batch tests and the microbial
      dynamics during this process was analyzed by polymerase chain reaction-denaturing
      gradient gel electrophoresis. The results showed that 100 mg l-1 of the dye was
      completely decolorized within 12 h, which was mainly caused by biodegradation.
      The optimal decolorization conditions were as follows: inoculation size 2.07 g l
      1 (wet cell pellet), rotation speed 150 r min-1, pH 5.0-7.0 and 30  degrees C.
      The processes were well described by zero-order kinetics, and more than 700 mg l
      1 of the dye would inhibit the activity of the consortium. Furthermore, the
      microbial community exhibited high efficiency in sequencing batch processes for
      continuous decolorization. Microbial community structure shifted obviously when
      exposed to higher concentration of the dye (500 mg l-1), and all the dominant
      microorganisms were affiliated with four different phyla of Actinobacteria,
      Bacteroidetes, Proteobacteria and Firmicutes.

PMID- 23975693
TI  - Biodegradation of malachite green by Ochrobactrum sp.
AB  - This study presents the biodegradation of malachite green (MG), a
      triphenylmethane dye, using a novel microorganism isolated from textile effluent
      contaminated environment. The organism responsible for degradation was identified
      as Ochrobactrum sp JN214485 by 16S rRNA analysis. The effect of operating
      parameters such as temperature, pH, immobilized bead loading, and initial dye
      concentration on % degradation was studied, and their optimal values were found
      to be 30  degrees C, 6, 20 g/L and 100 mg/L, respectively. The analysis showed
      that the extracellular enzymes were responsible for the degradation. The
      biodegradation of MG was confirmed by UV-visible spectroscopic and FTIR analysis.
      The phytotoxicity test concluded that the degradation products were less toxic
      compared to MG. The kinetics of biodegradation was studied and the activation
      energy was found to be 10.65 kcal/mol.

PMID- 23975694
TI  - Breeding and characterization of amino acid-analogue-resistant mutants of
      Arthrospira platensis.
AB  - To obtain amino acid-analogue-resistant mutants the wild strain A9 of Arthrospira
      platensis was mutated by ethylmethane sulfonate (EMS). Mutagenic effects of
      strain A9 by EMS were studied. The experimental results indicated that the
      survival rate curve of strain A9 took a typical "exponential shape" with lethal
      dosage of EMS being 1%. The survival of A9 strain was 13.2% when treated with
      0.4% of EMS, and the resistant mutation rates to two amino acid analogues, rho
      fluorophenylalanine (FPA) and L-canavanine sulphate (CS), were greatly increased
      with the highest rates being at 4.9 * 10(-4) and 3.24 * 10(-4), respectively. By
      repeated screening, two stable mutants resistant to amino acid analogues, A9f
      resistant to FPA and A9c resistant to CS, were obtained. Resistances of the two
      mutants to corresponding amino acid-analogues were both significantly increased.
      Compared with their parent strain A9, A9f appeared larger than A9 performance in
      filament diameter, spiral diameter, spiral pitch, filament length and spiral
      number, and A9c showed much longer length and spiral pitch than those of the
      initial strain. Analysis results on amino acids compositions and contents showed
      that both two mutants accumulated quite higher concentration of amino acids in
      cells. The two mutants might be excellent high amino acids producing strain. By
      this means two useful mutants with stable genetic makers for further genetic
      study of A. platensis were obtained, which laid a good foundation for further
      study on the transformation of A. platensis.

PMID- 23975696
TI  - Correlates of persisting posttraumatic symptoms in children and adolescents 18
      months after a cyclone disaster.
AB  - OBJECTIVE: To describe PTSD symptom persistence and resolution, including the
      potential phenomenon of late-onset PTSD, in children and adolescents 18 months
      after a cyclone disaster; and to investigate factors that predict longer-term
      symptom outcome. METHOD: 71 children and 191 adolescents who were screened three
      months after a Category 5 Cyclone were re-screened 18 months post-disaster. Child
      report measures included the PTSD Reaction Index, measures of event exposure and
      social connectedness. RESULTS: Approximately 1-in-5 children and 1-in-12
      adolescents endorsed cyclone-related PTSD symptoms at the moderate to severe
      level 18 months post-disaster. Of these approximately one-half (44.8%) of
      children were in the 'high-persister' group at 18-month follow-up. Persistence of
      low symptoms was very common (97.6%) and late-onset PTSD was a rare phenomenon.
      This pattern was similar in adolescents: 25.0% were in the 'high-persister' group
      and few students experienced late-onset PTSD. In multivariate analysis, only
      initial severe to very severe PTSD category made a significant independent
      contribution to explaining persisting moderate to severe PTSD symptoms in primary
      school students (ORadj=8.33, 95% CI=1.45-47.84). There was a trend for a similar
      result in secondary students. CONCLUSION: A child or adolescent with few PTSD
      symptoms three months post-disaster is likely to remain so unless a further
      traumatic event occurs. However, if symptomatic at three months, there is
      approximately a 30-45% chance that the child or adolescent will still be
      symptomatic 18 months after the disaster. Given the high rate of students in the
      'resolver' group, initial posttraumatic symptoms are a necessary but not
      sufficient condition for predicting chronic symptomatology. Other targets for
      predictive modelling include initial threat perception and high and low social
      connectedness.

PMID- 23975697
TI  - A female patient with depression and conversion disorder following brain tumor
      surgery.

PMID- 23975698
TI  - Clozapine-induced pneumonitis.

PMID- 23975700
TI  - Variation in the availability of cancer drug generics in the United States of
      America.
AB  - While most of the attention and spending in the oncology community in the United
      States has been focused on the remarkable scientific inventions of the newer
      targeted drugs, the shortage of the older essential cancer drugs that are off
      patent, mostly generics and injectables, has a threatening impact on the health
      of cancer patients, the execution of clinical trials and the identification of
      newer drugs and thus impacts upon the burden of costs and pressures on the health
      system in the United States. It is a part of the problem of the scarcity of
      generics across all medical specialties, but its oncology is particularly
      vulnerable. The problem in The United States has been increasing since the
      beginning of the 21st century until the 2011; since then there has been some
      improvement in 2012 and the first two quarters of 2013. In the second quarter of
      2012, there were 211 active shortages, down from 246 reports of active shortages
      in the same quarter of 2011. The Food and Drug Administration (FDA) officials
      ascribe the improvement to efforts that the agency made after President Obama
      issued an executive order in 2012 that impel the FDA to obtain early reports from
      companies about potential shortages. The drivers of the shortages are multi
      factorial. But are largely economic and are due to the lack of incentives to
      produce generics. There are efforts from the US government, politicians and the
      medical, pharmacy and oncology communities. However, the problem is still
      serious. There is a general agreement that efforts so far have not been adequate,
      and that there is a need for addressing effectively the fundamentals and the
      underlying causes. There is a lot that could be done in the United States and
      across the world to improve the accessibility of economically sustainable better
      value cancer drugs regardless of whether they are brand or generics and aiming at
      a win-win outcome for all stakeholders. 

PMID- 23975699
TI  - Cost comparison and economic implications of commonly used originator and generic
      chemotherapy drugs in India.
AB  - Cancer treatments have improved outcomes but access to medications is an issue
      around the world and especially so in low- and middle-income countries, such as
      India. Generic substitution may lead to significant cost savings. The author
      aimed to compare the cost and estimate potential cost savings per cycle, per
      patient, and for the country as a whole with generic substitution of frequently
      used chemotherapy drugs in the treatment of common cancers in India. Generic
      paclitaxel (Taxol), docetaxel (Taxotere), gemcitabine, oxaliplatin and irinotecan
      cost from 8.9% to 36% of their equivalent branded originator drug, resulting in
      cost savings of ~ Indian Rupees (INR) 11,000 to >INR 90,000 (USD 200-1600, Euro
      160-1300) per cycle; and ~INR 50,000 to >INR 240,000 (USD 900-4300, Euro 700
      3400) per patient. Overall, potential yearly savings for health systems in India
      were nearly INR 47 billion (~USD 843 million, Euro 670 million). In conclusion,
      generic substitution for frequently used chemotherapy drugs in the treatment of
      common cancers has an enormous potential to generate significant cost savings and
      increase access to cancer treatments in India and other low- and middle-income
      countries.

PMID- 23975701
TI  - Anti-neoplastic biosimilars--the same rules as for cytotoxic generics cannot be
      applied.
AB  - Biopharmaceuticals are complex protein molecule drugs produced by living
      organisms. Biopharmaceuticals as anti-neoplastic monoclonal antibodies are a
      major breakthrough in oncology. When the patent of innovator biopharmaceuticals
      expires, copies will be introduced. These copies are after approval by European
      Medicines Agency (EMA) within EU called biosimilars and have their own regulatory
      pathways which differ from the chemical generics approval process. The main
      reason is that identical copies of chemical molecules via chemical syntheses can
      be produced but copies of innovator biopharmaceuticals will only be similar. An
      extensive comparability exercise has to be carried out between the reference
      product and the biosimilar before approval. However, still there might be
      differences between the innovator anti-neoplastic monoclonal antibody and the
      biosimilar anti-neoplastic antibody which cannot be detected until extended
      clinical studies have been carried out. Moreover, all indications for an anti
      neoplastic biosimilar antibody may not have been tested for at the time of
      approval but extrapolated based on the indications of the reference monoclonal
      antibody. The limited information on biosimilar anti-neoplastic monoclonal
      antibodies at approval may still be justified taking into account that the aim is
      to reduce price. However, the risk-benefit ratio for biosimilar anti-neoplastic
      monoclonal antibodies should be carefully evaluated, considering that anti
      neoplastic monoclonal antibody therapy has a curative intent, price reduction so
      far within EU of biosimilars is modest and that in the end only part of the total
      costs for cancer health care is related to biopharmaceuticals. 

PMID- 23975702
TI  - The role of generic medicines and biosimilars in oncology in low-income
      countries.
AB  - Cancer cases are rising in developing countries which are already grappling with
      high levels of infectious diseases including human immunodeficiency
      virus/acquired immunodeficiency syndrome (HIV/AIDS), tuberculosis (TB) and
      malaria. The United Nations (UN) including the World Health Organisation (WHO)
      have called on member states to establish strategies to deal with the increasing
      burden of non-communicable diseases, including cancer, in developing countries.
      The complexity of cancer care and management calls for innovative approaches in
      low resource settings especially since these settings are already grappling with
      huge challenges in healthcare including lack of funds, weak human resource base
      and lack of treatment guidelines. Whilst the cost of medications is by no means
      the only high cost in cancer care, the availability of affordable anti-cancer
      generic drugs and biologically similar therapeutic agents (biosimilars) will go a
      long way to reduce overall cost of cancer care. The high cost of anticancer
      medicines has been cited among the reasons whilst patients default in treatment.
      Non-proprietary anti-cancer agents--generics and biosimilars--often cost several
      times lower than their innovator branded counterparts. They can reduce the cost
      of care significantly and their multi-source origin often provide guarantee in
      supply. The use of generic and biosimilar products is hinged on the assumption
      that they are of assured quality and of the same pharmaceutical integrity as
      their innovator counterparts. The use of these products however is associated
      with challenges that must be understood and addressed. The quality of all
      generics and biosimilars should be rigorously controlled and assured. Measures to
      prevent counterfeit and sub-standard generics and biosimilars should be developed
      and the cold-chain must be maintained for all biosimilars. In addition to these,
      the WHO is encouraged to develop a prequalification scheme to assist countries
      without strong regulatory systems to procure anticancer generics and biosimilars
      of assured quality.

PMID- 23975703
TI  - Generic drugs: their role in better value cancer care.

PMID- 23975695
TI  - Comparison of bacterial communities of biofilms formed on different membrane
      surfaces.
AB  - Bacterial biofilm communities formed on different membrane surfaces were
      investigated based on 16S rRNA gene sequence analysis. The biofilm communities
      were distinct from those of mixed-liquor and consisted mainly of Beta- and
      Gammaproteobacteria. Sequences of Xathomonas and Aquabacterium were mostly
      retrieved from the biofilm samples rather than from the mixed liquor.
      Furthermore, statistical analyses demonstrated the importance of a physico
      chemical property of membrane, surface roughness, in structuring the bacterial
      biofilm communities. 

PMID- 23975704
TI  - Clinical and economic implications of the use of nanoparticle paclitaxel
      (Nanoxel) in India.
AB  - Paclitaxel (Taxol), one of the most commonly used chemotherapeutic agents, is
      poorly soluble in water and requires cremophor, which often causes infusion
      reactions, as a solvent. Nanoxel, a nanoparticle formulation of the taxane, has
      been approved by the Indian regulatory authority. In the present article, we aim
      to describe the experience with the use of Nanoxel in India and its clinical and
      economic implications. We present three retrospective series in a common practice
      environment and an economic model. The first series shows no reactions in 596
      Nanoxel infusions; the second series shows comparable adverse events other than
      infusion reactions between 83 patients who received Nanoxel and 32 treated with
      conventional paclitaxel. The third reveals comparable clinical outcomes for 51
      patients treated with Nanoxel or conventional paclitaxel for gastroesophageal
      tumors. Finally, we describe an economic model which estimates savings of 21 580
      Indian rupees per cycle with Nanoxel vis-a-vis conventional paclitaxel in the
      treatment of solid tumors in India. In conclusion, in an era in which the
      greatest challenge we face as medical oncologists is how to conciliate hard-won
      and incremental--but small--improvements in survival with exponentially rising
      drugs costs, it is refreshing to see a potential new formulation of a commonly
      used drug that may actually generate cost-savings while improving clinical
      outcomes and patient well-being. Further studies are clearly warranted to
      determine the optimal dose and schedule for Nanoxel as well as its comparative
      effectiveness to cremophor-based paclitaxel.

PMID- 23975705
TI  - Mining and the environment.

PMID- 23975707
TI  - Scientific derivation of environmental quality benchmarks for the protection of
      aquatic ecosystems: challenges and opportunities.

PMID- 23975708
TI  - Response to comment of Dr Kamal Chaouachi on "Shisha smoking, nickel and chromium
      levels in Tunisia".

PMID- 23975709
TI  - Pesticide risk assessment and management in a globally changing world--report
      from a European interdisciplinary workshop.

PMID- 23975710
TI  - The double-edged sword of humic substances: contrasting their effect on
      respiratory stress in eastern rainbow fish exposed to low pH.
AB  - High amounts of humic substances (HS) are commonly found in natural acidic
      waterways and have been suggested to offer some protection against low pH. This
      study investigated the ability of HS to decrease respiratory stress in eastern
      rainbowfish (Melanotaenia splendida splendida) exposed to decreases in pH (range
      of 7-3.5) in soft and hard water. Repeated measures ANOVA revealed a significant
      difference in respiration (time taken for ten operculum movements) between pH and
      HS treatments, with a significant interaction between pH and HS present in 5/6
      trials. Respiratory stress was shown to increase with increasing acidity, but
      significantly decreased in treatments with HS (10 and 20 mg/L) compared to those
      without. The fish exposed to pH treatments without HS also displayed increased
      hyperactivity, larger operculum movements and increased mucous production.
      Increased morbidity was shown in HS treatments at pH 3.5 (soft water) and at pH 4
      (hard water) compared to treatment without HS. This indicates that HS is helpful
      in ameliorating the effects of decreased pH on respiration at sublethal pH
      levels; however, as pH decreases further, it seems that HS increases the toxicity
      (morbidity) of the low pH.

PMID- 23975711
TI  - Impact of wastewater treatment plants on receiving surface waters and a tentative
      risk evaluation: the case of estrogens and beta blockers.
AB  - Five estrogenic hormones (unconjugated + conjugated fractions) and 10 beta
      blockers were analyzed in three wastewater treatment plant (WWTP) effluents and
      receiving river waters in the area of Lyon, France. In the different samples,
      only two estrogens were quantified: estrone and estriol. Some beta blockers, such
      as atenolol, acebutolol, and sotalol, were almost always quantified, but others,
      e.g., betaxolol, nadolol, and oxprenolol were rarely quantified. Concentrations
      measured in river waters were in the nanogram per liter range for estrogens and
      between 0.3 and 210 ng/L for beta blockers depending on the substance and the
      distance from the WWTP outfall. The impact of the WWTP on the receiving rivers
      was studied and showed a clear increase in concentrations near the WWTP outfall.
      For estrogens, the persistence in surface waters was not evaluated given the low
      concentrations levels (around 1 ng/L). For beta blockers, concentrations measured
      downstream of the WWTP outfall were up to 16 times higher than those measured
      upstream. Also, the persistence of metoprolol, nadolol, and propranolol was noted
      even 2 km downstream of the WWTP outfall. The comparison of beta blocker
      fingerprints in the samples collected in effluent and in the river also showed
      the impact of WWTP outfall on surface waters. Finally, a tentative environmental
      risk evaluation was performed on 15 sites by calculating the ratio of receiving
      water concentrations to predicted non-effect concentrations (PNEC). For
      estrogens, a total PNEC of 5 ng/L was considered and these substances were not
      linked to any potential environmental risk (only one site showed an environmental
      risk ratio above 1). Unfortunately, few PNECs are available and risk evaluation
      was only possible for 4 of the 10 beta blockers studied: acebutolol, atenolol,
      metoprolol, and propranolol. Only propranolol presented a ratio near or above 1,
      showing a possible environmental risk for 4 receiving waters out of 15.

PMID- 23975712
TI  - Sublethal Cd-induced cellular damage and metabolic changes in the freshwater crab
      Sinopotamon henanense.
AB  - To explore whether sublethal cadmium (Cd) exposure causes branchial cellular
      damages and affects the metabolic activity in brachyuran crustaceans, the
      freshwater crab Sinopotamon henanense was exposed to 0.71, 1.43, and 2.86 mg/L
      Cd(2+) for 3 weeks. Gill morphology, metabolic activity (activities of isocitrate
      dehydrogenase (IDH), cytochrome c oxidase (CCO) and lactate dehydrogenase (LDH),
      mRNA expression of CCO active subunit 1 (cco-1) and ldh, as well as ATP levels)
      in crab muscle were investigated. The results showed that sublethal Cd exposure
      caused profound morphological damages in the gills. The branchial epithelial
      cells were disorganized and vacuolized. Ultrastructurally, a decrease in number
      of apical microvilli, vacuolized mitochondria, and condensed chromatin were
      observed in gill epithelial cells. Correspondingly, the Cd exposure also induced
      downregulations of cco-1 and ldh mRNA expression and reduced activities of IDH,
      CCO, and LDH, in accordance with the lower ATP level in crab muscle. These
      results led to the conclusion that gill damage caused by sublethal Cd exposure
      could lead to an impairment of oxygen uptake of S. henanense, and the inhibition
      of metabolic activity decreases the oxygen demand of the crab and assists them to
      survive under the condition of lower oxygen availability. These effects add to
      our understanding on toxic effects of Cd and survival management of S. henanense
      subchronically exposed to sublethal Cd.

PMID- 23975713
TI  - Trace metal and metalloid levels in surface water of Marcal River before and
      after the Ajka red mud spill, Hungary.
AB  - The aim of this study was to compare and assess the dissolved concentrations of
      trace elements (As, Zn, Hg, Cd, Cr, Ni, Pb and Cu) in surface water of Marcal
      River before and after the red mud spill that occurred in Ajka, western Hungary,
      in October 2010. The caustic sludge flooded the surrounding settlements and
      polluted the nearby Torna Creek, which flows through the Marcal and Raba rivers
      into the Danube. A total of 92 surface water samples were collected from the
      Marcal River in the period of 2007-2012 and analysed for dissolved trace
      metal(loid)s by atomic absorption spectroscopy method. After the spill, the water
      management authority initially focused on acid dosing of surface waters to lower
      pH and was effective in lowering both pH and metal(loid) concentrations. Among
      the dissolved trace metal(loid)s, arsenic and nickel levels were moderately
      higher in the Marcal River 2 years since the spill compared to that observed in
      the pre-disaster period. The concentrations of dissolved trace metal(loid)s did
      not exceed the European water quality standards and the US Environmental
      Protection Agency aquatic life criteria values (excluding one sample for
      cadmium). 

PMID- 23975715
TI  - Radial artery for coronary artery bypass grafting: does proximal anastomosis to
      the aorta or left internal mammary artery achieve better patency?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was 'in coronary artery bypass grafting using
      radial artery grafts, does proximal anastomosis to the aorta or left internal
      mammary artery achieve better patency'. Altogether >183 papers were found using
      the reported search, of which 9 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. Radial artery grafts typically have a narrower lumen than vein grafts,
      and as such there is some concern that anastomosing them directly to the aorta
      during coronary artery bypass grafting (CABG) may impair graft patency. As such,
      some surgeons prefer to anastomose radial artery grafts to a second-order vessel
      such as the left internal mammary artery (LIMA). We sought to assess the evidence
      for this. A handful of papers directly addressing the issue of the effect of the
      site of proximal anastomosis on graft patency were found, with three showing no
      significant difference. One such study reported an insignificant difference in
      angiographic patency at 32 months postoperatively, with 94.1% of off-aorta grafts
      remaining patent vs 87.2% of off-LIMA grafts (p = 0.123). However, a large-scale
      well-designed study was able to demonstrate a statistically significant
      difference at five years postoperatively, with 74.3% of off-aorta grafts patent,
      compared with 65.2% of off-LIMA (p = 0.004). Nonetheless, a number of papers that
      report patency for either off-aorta or off-LIMA grafts give comparable figures
      for each technique. Additionally, different centres and investigators report very
      different patency results for grafts that have the same site of proximal
      anastomosis. One centre was able to achieve patency rates for off-LIMA grafts of
      88% up to a mean of 7.7 years postoperatively while another centre reported a
      patency rate of only 78.6% at three years. Given this, and the plethora of other
      factors influencing graft patency, we conclude that the best evidence suggests
      that the site of proximal anastomosis has little or no effect on radial artery
      graft patency following CABG. 

PMID- 23975714
TI  - Epigenetic control of heavy metal stress response in mycorrhizal versus non
      mycorrhizal poplar plants.
AB  - It was previously shown that arbuscular mycorrhizal fungi (AMF) exert a
      significant improvement of growth in a tolerant white poplar (Populus alba L.)
      clone (AL35) grown on Cu- and Zn-polluted soil via foliar alterations in the
      levels of defence/stress-related transcripts and molecules. However, nothing is
      known about the epigenetic changes which occur during tolerance acquisition in
      response to heavy metals (HMs) in the same mycorrhizal vs. non-mycorrhizal poplar
      plants. In order to analyse the epigenome in leaves of AL35 plants inoculated or
      not with AMF and grown in a greenhouse on multimetal polluted or unpolluted soil,
      the Methylation Sensitive Amplification Polymorphism (MSAP) approach was adopted
      to detect cytosine DNA methylation. Modest changes in cytosine methylation
      patterns were detected at first sampling (4 months from planting), whereas
      extensive alterations (hypomethylation) occurred at second sampling (after 6
      months) in mycorrhizal plants grown in the presence of HMs. The sequencing of
      MSAP fragments led to the identification of genes belonging to several Gene
      Ontology categories. Seven MSAP fragments, selected on the basis of DNA
      methylation status in treated vs control AL35 leaves at the end of the
      experiment, were analysed for their transcript levels by means of qRT-PCR. Gene
      expression varied in treated samples relative to controls in response to HMs
      and/or AMF inoculation; in particular, transcripts of genes involved in RNA
      processing, cell wall and amino acid metabolism were upregulated in the presence
      of AMF with or without HMs.

PMID- 23975716
TI  - Conservative management of a tracheal leakage occurring 40 days after robotic
      thyroidectomy.

PMID- 23975717
TI  - Letter to the editor: expression of concern, reaffirmed.

PMID- 23975718
TI  - Children's knowledge and beliefs about medicines.
AB  - Minor illnesses in children are often cured at home with over the counter
      medicines. Even though there is a wide use of medicines among children, they
      rarely receive medical advice about their medications from doctors or
      pharmacists. The aim of this study is to evaluate children's beliefs about
      medicines as well as to explain what children know about medicines. A cross
      sectional survey was used to collect data from four primary schools in Penang
      Island, Malaysia. The target population of this research was schoolchildren of 11
      and 12 years old regardless of their gender and social status. A self
      administration questionnaire was used to obtain the data from schoolchildren and
      their parents. After including all schoolchildren in grades five and six, the
      total sample size was 1000 children in addition to 1000 parents. This study found
      that most children have inadequate knowledge and false beliefs about the efficacy
      of medicines. Children's beliefs about the efficacy of medicines were affected by
      their age group, gender and race (p < .05). Females, older children and Chinese
      were more knowledgeable about the efficacy of medicines. Furthermore, the socio
      economic status, parents' education level and parents' occupation influenced
      children's beliefs about medicines (p < .001). This study showed that children
      have misconception about medicines. The need for medicine education should be
      implemented to get more knowledgeable users of medicines in future. However, the
      role of health-care professional should be increased in terms of medicine
      education. 

PMID- 23975719
TI  - Use of the national quality registry to monitor health-related quality of life of
      children with type 1 diabetes: a pilot study.
AB  - The management of diabetes is complicated, as treatment affects the everyday life
      of both children and their families. To enable optimal care for children with
      type 1 diabetes, it is important to highlight health-related quality of life
      (HrQoL) as well as medical outcomes to detect psychological problems that
      otherwise could be missed. The aim was to study HrQoL in children and adolescents
      with type 1 diabetes dependent on gender, age and co-morbidity and to study the
      consistency between children's self-reporting and parents' proxy reporting. The
      cross-sectional data were collected using the questionnaire DISABKIDS Chronic
      Generic Measure and the DISABKIDS diabetes module. Parents in the proxy report
      perceived their children's HrQoL to be lower than children themselves. Boys
      reported their HrQoL to be better than girls. Results show that living with an
      additional disease has an impact on the HrQoL, which is an important factor to
      consider in the quality registry. Assessing HrQoL on a routine basis may
      facilitate detection and discussion of HrQoL-related questions in the national
      quality registry. 

PMID- 23975720
TI  - Reflection: moving from a mandatory ritual to meaningful professional
      development.
AB  - Reflection has become established as a key principle underpinning maintenance of
      standards within professional education and practice. A requirement to evidence
      reflection within performance review is intended to develop a transformative
      approach to practice, identify developmental goals, and ultimately, improve
      healthcare. However, some applications have taken an excessively instrumental
      approach to the evidencing of reflection, and while they have provided useful
      templates or framing devices for recording individualistic reflective practice,
      they potentially have distorted the original intentions. This article revisits
      the educational theory underpinning the importance of reflection for enhancing
      performance and considers how to enhance its value within current paediatric
      practice. 

PMID- 23975721
TI  - Is it farewell to codeine?

PMID- 23975722
TI  - Systematic identification of Class I HDAC substrates.
AB  - Lysine acetylation is a common post-translational modification of histone and non
      histone proteins. This process has an important function in regulating
      transcriptional activities and other biological processes. Although several
      computer programs have been developed to predict protein acetylation sites,
      deacetylases responsible for known or predicted acetylation sites remain unknown.
      In this research, Class I histone deacetylases (HDACs) substrates were manually
      obtained, and sequence features of deacetylation sites were analyzed. We found
      that three members of Class I HDACs (HDAC1, HDAC2 and HDAC3) shared similar
      sequence features. Therefore, a method was proposed to identify the substrates of
      Class I HDACs. We evaluated the efficiency of the prediction based on P-value
      distribution analysis and leave-one-out test. To validate the result of the
      prediction, we overexpressed Class I HDACs in cells and detected the acetylation
      levels of potential substrates. In the experiment, five of the seven predicted
      proteins were deacetylated by Class I HDACs. These results suggested that our
      method could effectively predict protein deacetylation sites. The work has been
      integrated to the website ASEB, which was freely available at
      http://cmbi.bjmu.edu.cn/huac. 

PMID- 23975723
TI  - Improvement in albuminuria in patients with type 2 diabetes after laparoscopic
      adjustable gastric banding.
AB  - PURPOSE: To determine the effects of laparoscopic adjustable gastric banding
      (LAGB) on albuminuria in patients with obesity, type 2 diabetes mellitus (T2DM)
      and established diabetic nephropathy. METHODS: A retrospective analysis of
      clinical records from a tertiary diabetes service identified obese patients with
      T2DM who had micro- or macroalbuminuria prior to LAGB surgery. Clinical data from
      follow-up appointments including albuminuria were analysed. RESULTS: A total of
      23 T2DM patients were included in the final study. Of 7 patients with
      macroalbuminuria at baseline, 2 reverted to normoalbuminuria, 2 reverted to
      microalbuminuria and 3 remained with macroalbuminuria on their final recording in
      the 36-month period of follow-up. Of 16 patients with microalbuminuria, 9
      reverted to normoalbuminuria, while 6 remained with microalbuminuria. CONCLUSION:
      This study demonstrates significant improvements in albuminuria in patients with
      established diabetic nephropathy following LAGB. These results suggest the
      potential for LAGB to improve or reverse renal damage in patients with T2DM.

PMID- 23975724
TI  - Trends in control of cardiovascular risk factors among US adults with type 2
      diabetes from 1999 to 2010: comparison by prevalent cardiovascular disease
      status.
AB  - BACKGROUND: Most patients with type 2 diabetes mellitus (T2DM) suffer from
      cardiovascular disease (CVD). Whether CVD risk factors have improved in those
      with DM with and without CVD is not established. We compared risk factor levels
      and goal attainment in US adults with diabetes with and without CVD. METHODS: We
      examined 2403 adults (aged >= 18 years) in the United States with T2DM (n = 654,
      27% with CVD) across 1999-2010 using the US National Health and Nutrition
      Examination Survey (NHANES) and evaluated control of hemoglobin A1c (HbA1c),
      blood pressure (BP), low-density lipoprotein cholesterol (LDL-C) and body mass
      index (BMI) in those with DM with versus without CVD. RESULTS: The proportions
      controlled for HbA1c, BP and LDL-C have improved (p < 0.001) overall between 1999
      and 2010, but only 24% were at goal for all three factors in 2009-2010. There
      were improvements in BP, triglycerides and LDL-C in those with CVD, and in those
      without CVD, there were also improvements in control of all parameters, although
      changes in mean levels of risk factors were less impressive. CONCLUSION: Despite
      modest improvement over time, in most CVD risk factors, only one-fourth of those
      with T2DM are at goal for HbA1c, BP and LDL-C, with improvements seen in those
      without CVD more often than those with CVD.

PMID- 23975725
TI  - Increase of angiotensin-converting enzyme activity and peripheral sympathetic
      dysfunction could contribute to hypertension development in streptozotocin
      induced diabetic rats.
AB  - Diabetes augments the risk of hypertension. Although several factors have been
      implicated in the development of such hypertensive state, we designed this study
      to investigate blood pressure development, the activity of angiotensin-converting
      enzyme (ACE) in blood as well as sympathetic neurotransmission in the vas
      deferens of diabetic rats. We used streptozotocin (STZ)-induced diabetic rats (60
      mg/kg) in order to evaluate the systolic blood pressure (SBP), ACE activity and
      peripheral sympathetic neurotransmission. We observed the following changes of
      parameters: increase of SBP, decrease of heart rate, augmentation of plasma ACE
      activity, enhancement of phasic and tonic vas deferens contractions elicited by
      electrical stimulation at 5 Hz, increase of maximal response to noradrenaline
      (NA) and decrease of adenosine triphosphate (ATP)-elicited contraction of vasa
      deferentia. The results reveal that in the development of hypertension in
      diabetic rats, augmentation of circulating ACE activity precedes the sympathetic
      dysfunction. Additionally, it seems that the purinergic and noradrenergic
      neurotransmission is compromised. 

PMID- 23975726
TI  - Assessment of endothelial dysfunction in patients with impaired glucose tolerance
      during a cold pressor test.
AB  - The objective of this study is to explore changes in microvascular tone during a
      contralateral cold pressor test and to compare the results obtained in healthy
      subjects and in patients with impaired glucose tolerance (IGT) and type 2
      diabetes. Low-amplitude fluctuations of skin temperature in the appropriate
      frequency ranges were used as a characteristic for the mechanism for vascular
      tone regulation. In total, 13 adults with type 2 diabetes aged 40-67 years and 18
      adults with IGT aged 31-60 years participated in this pilot study. The control
      group included 12 healthy men and women aged 39-60 years. The response to the
      cold pressor test in patients with type 2 diabetes and with IGT differs
      essentially from that of healthy subjects in the endothelial frequency range.
      Endothelial dysfunction occurs in the preclinical stage of diabetes and
      manifests, in particular, as a disturbance of the endothelial part of vascular
      tone regulation. 

PMID- 23975727
TI  - A forensic path to RGC-5 cell line identification: lessons learned.
AB  - In 2001, a transformed cell line RGC-5 was developed from the rat retina that was
      thought to be of retinal ganglion cell origin. Since that time many investigators
      have used this line in a wide variety of studies to understand better retinal
      ganglion cell activity, cell signaling, and neuroprotection. Recently, a
      publication emerged that claimed that this RGC-5 cell line was derived from mouse
      and not rat, and other studies also indicated the expression of certain proteins
      that typically were not associated with retinal ganglion cells. This certainly
      came as a shock not only to the originators of this cell line, but also to others
      who have been using this as an in vitro model of rat retinal ganglion cells. As a
      result, we undertook experiments to determine if the RGC-5 cell line currently in
      use may have been mischaracterized. We, indeed, found that the RGC-5 cell line
      was of mouse and not rat origin, as was claimed originally in the original
      research report. We further determined whether these cells were of retinal
      ganglion origin. Our findings showed conclusively that RGC-5 cells were, indeed,
      of mouse origin and, using additional cytogenetic profile testing, karyotyping,
      and genetic and protein profiling, we concluded that these cells were not of
      retinal ganglion cell origin, but were the cell line 661W, a mouse SV-40 T
      antigen transformed photoreceptor cell line. The 661W cell line also was present
      in the laboratory of the originating laboratory and probably resulted in cross
      contamination. The present study reviews some of the errors that were made in
      misidentifying the RGC-5 cell line and offers some insight as to how this may
      have happened, and ways one can avoid mischaracterization of a potentially
      important cell line.

PMID- 23975728
TI  - The use of cell lines to "model" ocular tissues: cautionary tales.

PMID- 23975730
TI  - Anticholinergic component of the Drug Burden Index and the Anticholinergic Drug
      Scale as measures of anticholinergic exposure in older people in New Zealand: a
      population-level study.
AB  - BACKGROUND: Older people are exposed to multiple medicines that possess
      anticholinergic properties. The use of anticholinergic medicines is associated
      with the risk of morbidity, mortality and cognitive decline, particularly in
      older people. Anticholinergic exposure can be measured using tools such as the
      Drug Burden Index-Anticholinergic component (DBI-ACh) and the Anticholinergic
      Drug Scale (ADS). OBJECTIVE: The aim of this population-level study was to
      determine the extent of anticholinergic exposure in older people, particularly
      among those receiving acetylcholinesterase inhibitors in New Zealand. METHODS:
      The study used data extracted from Pharmaceutical Claims Data Mart (Pharms) for
      the year 2011. A total of 537,387 individuals aged 65 years and older were
      included in the study, of whom 45.10 % were men. Individuals dispensed donepezil
      at any time during 2011 were selected as the acetylcholinesterase inhibitor
      (AChEI) group (n = 4,258) and the remainder were included in the non
      acetylcholinesterase inhibitor (non-AChEI) group (n = 533,129). Anticholinergic
      exposure was measured using the DBI-ACh and the ADS. RESULTS: Analysis of the
      Pharms dataset revealed that, in 2011, anticholinergic exposure as defined by the
      DBI-ACh and the ADS was 31.80 % and 52.66 %, respectively. The mean number of
      medicines dispensed was 5.64 +/- 3.91 (+/- SD) with a 95 % confidence interval of
      5.63-5.65. In the AChEI group, anticholinergic exposure using the DBI-ACh and the
      ADS was 42.93 % (median 0; interquartile range (IQR) 1) and 58.50 % (median 0;
      IQR 0), respectively. ADS level 3 medicines such as amitriptyline, nortriptyline
      and oxybutynin were commonly prescribed in both groups. Amitriptyline,
      nortriptyline, oxybutynin and paroxetine are medicines considered to have
      significant anticholinergic potency. Of these medicines, nortriptyline and
      oxybutynin were more frequently prescribed in individuals taking donepezil.
      CONCLUSIONS: A significant proportion of older people are exposed to medicines
      with anticholinergic properties, including those dispensed acetylcholinesterase
      inhibitors. Further research is required to explore associations between
      different measures of anticholinergic exposure and clinically relevant outcomes
      in older people on a population level.

PMID- 23975732
TI  - Cholinergic enhancement differentially modulates neural response to encoding
      during face identity and face location working memory tasks.
AB  - Potentiation of cholinergic transmission influences stimulus processing by
      enhancing signal detection through suppression and/or filtering out of irrelevant
      information (bottom-up modulation) and with top-down task-oriented executive
      mechanisms based on the recruitment of prefrontal and parietal attentional
      systems. The cholinergic system also plays a critical role in working memory (WM)
      processes and preferentially modulates WM encoding, likely through stimulus
      processing mechanisms. Previous research reported increased brain responses in
      visual extrastriate cortical regions during cholinergic enhancement in the
      encoding phase of WM, independently addressing object and spatial encoding. The
      current study used functional magnetic resonance imaging to determine the effects
      of cholinergic enhancement on encoding of key visual processing features.
      Subjects participated in two scanning sessions, one during an intravenous (i.v.)
      infusion of saline and the other during an infusion of the acetylcholinesterase
      inhibitor physostigmine. In each scan session, subjects alternated between a face
      identity recognition and a spatial location WM. Enhanced cholinergic function
      increased neural activity in the ventral stream during encoding of face identity
      and in the dorsal stream during encoding of face location. Conversely, a
      reduction in brain response was found for scrambled sensorimotor control images.
      The cholinergic effects on neural activity in the ventral stream during encoding
      of face identity were stronger than those observed in the dorsal stream during
      encoding of face location, likely as a consequence of the role of acetylcholine
      in establishing the inherently relevant nature of face identity. Despite the
      limited sample-size, the results suggest the stimulus-dependent role of
      cholinergic system in signal detection, as they show that cholinergic
      potentiation enhances neural activity in regions associated with early perceptual
      processing in a selective manner depending on the attended stimulus feature. 

PMID- 23975731
TI  - BH3-only protein Noxa contributes to apoptotic control of stress-erythropoiesis.
AB  - Apoptosis plays an essential role in the control of erythropoiesis under normal
      and pathological conditions. However, the contribution of individual proteins
      within cell death signalling pathways remains poorly defined. Here, we
      investigated the role of the pro-apoptotic Bcl-2 family member Noxa in the
      regulation of erythropoiesis. We found that expression of Noxa is induced during
      erythroid differentiation of human and murine precursor cells. Using in vitro
      model systems for erythroid progenitors, we observed rapid induction of Noxa upon
      cytokine deprivation. Knockdown or deletion of Noxa conferred significant
      protection against apoptosis upon cytokine withdrawal. In vivo, Noxa deficiency
      did not affect hematological blood parameters or erythroid progenitor composition
      of bone marrow and spleen under steady-state conditions. In contrast, in a model
      of acute haemolytic anemia, Noxa-deficiency enhanced hematocrit recovery.
      Moreover, in a model of chronic inflammation-induced anemia, Noxa-ablation
      resulted in a dramatic increase of erythroblast expansion. Our data indicate that
      induction of Noxa in erythroid progenitors sets a survival threshold that limits
      expansion beyond the number of cells that can be sustained by the available
      cytokines, which becomes apparent under conditions of induced anemia.

PMID- 23975734
TI  - Genetic variants in SLC7A7 are associated with risk of glioma in a Chinese
      population.
AB  - Dysregulation of the amino acid transporter SLC7A7 is involved in multiple types
      of cancer including gliobastoma (GBM), the most malignant form of glioma. We
      hypothesized that SLC7A7 genetic variants may influence glioma risk. To test this
      hypothesis, we conducted a case-control study in 736 incident glioma cases and
      793 cancer-free controls in a Chinese population by genotyping 22 common single
      nucleotide polymorphisms in SLC7A7. In single-locus analysis, we found an
      increased risk was associated with the variant genotypes of rs12888930 (adjusted
      odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.02-1.54, P = 0.034),
      rs12433985 (adjusted OR = 1.38, 95%CI = 1.13-1.70), rs2065134 (adjusted OR =
      1.43, 95% CI 1.05-1.95) in a dominant genetic model and rs12436190 (adjusted OR =
      1.37, 95%CI 1.06-1.77) in a recessive model. Multivariate analysis confirmed that
      rs12433985 and rs2065134 were significant and independent risk factor for glioma
      as well as GBM subtype (for rs12433985, OR = 1.21, 95%CI 1.04-1.42, P = 0.016 for
      all types of gliomas and P = 0.013, OR = 1.30, 95%CI 1.06-1.60 for GBM. For
      rs2065134, OR = 1.39, 95%CI 1.02-1.89, P = 0.039 for all types of gliomas and OR
      = 1.66, 95%CI 1.12-2.24, P = 0.011). These results, for the first time, provide
      suggestive evidence of polymorphisms in SLC7A7 is involved in the aetiology of
      glioma.

PMID- 23975733
TI  - DNA methyltransferase inhibitor-mediated apoptosis in the Wnt/beta-catenin signal
      pathway in a renal cell carcinoma cell line.
AB  - The Wnt signaling pathway is activated in most cancer types when Wnt antagonist
      genes are inactivated. Glycogen synthase kinase 3 (GSK3beta) is an important
      regulator of the Wnt/beta-catenin signaling pathway. The mechanisms underlying
      GSK3beta regulation of neoplastic transformation and tumor development are
      unclear. Studies have raised the possibility that the Wnt signaling pathway may
      be implicated in renal cell carcinoma (RCC). Therefore, in the present study, we
      hypothesize that the expression and methylation status of the secreted frizzled
      related protein 2 (sFRP2) gene, one of the secreted antagonists that bind Wnt
      protein, and re-expression of this gene with the demethylation agent (5-aza-2'
      deoxycytidine; DAC) may induce apoptosis in RCC cells. To test this hypothesis,
      we investigated the relationship among epigenetic inactivation of sFRP2 and p
      GSK3beta (Ser9) and other Wnt antagonists (sFRP1, DKK3, WIF-1) and apoptotic
      factors (Bax and Caspase3) as well as the anti-apoptotic factor BCL2. Our results
      indicate that DAC-mediated inhibition of DNA methylation led to a re-activation
      of sFRP2 expression and increased expression levels of the Wnt antagonists and
      apoptotic factors. In contrast, the level of beta-catenin (CTNNB1) expression
      decreased. The p-GSK3beta (Ser9) protein level in Caki-2 cells was significantly
      down-regulated, while the DNA fragmentation rate increased after treatment with 5
      MUM DAC at 96 h. Our data show that sFRP2 functions as a tumor suppressor gene in
      RCC and that its restoration may offer a new therapeutic approach for the
      treatment of RCC. Moreover, our study draws attention to the regulatory features
      of epigenetic molecules and analyses their underlying molecular mechanisms of
      action and their potential use in clinical practice.

PMID- 23975735
TI  - High interpatient variability of raltegravir CSF concentrations in HIV-positive
      patients: a pharmacogenetic analysis.
AB  - OBJECTIVES: To analyse the determinants of raltegravir CSF penetration, including
      the pharmacogenetics of drug transporters located at the blood-brain barrier or
      blood-CSF barrier. METHODS: Plasma and CSF raltegravir concentrations were
      determined by a validated HPLC coupled with mass spectrometry method in adults on
      raltegravir-based combination antiretroviral therapy undergoing a lumbar
      puncture. Single nucleotide polymorphisms in the genes encoding drugs
      transporters (ABCB1 3435, SLCO1A2, ABCC2 and SLC22A6) and the gene encoding
      hepatocyte nuclear factor 4 alpha (HNF4alpha) were determined by real-time PCR.
      RESULTS: In 41 patients (73.2% male, 95.1% Caucasians), the median raltegravir
      plasma and CSF concentrations were 165 ng/mL (83-552) and 31 ng/mL (21-56),
      respectively. CSF-to-plasma ratios (CPRs) ranged from 0.005 to 1.33 (median 0.20,
      IQR 0.04-0.36). Raltegravir trough CSF concentrations (n = 35) correlated with
      raltegravir plasma levels (rho = 0.395, P = 0.019); CPRs were higher in patients
      with blood-brain barrier damage (0.47 versus 0.18, P = 0.02). HNF4alpha 613 CG
      genotype carriers had lower trough CSF concentrations (20 versus 37 ng/mL, P =
      0.03) and CPRs (0.12 versus 0.27, P = 0.02). Following multivariate linear
      regression analysis, the CSF-to-serum albumin ratio was the only independent
      predictor of raltegravir penetration into the CSF. CONCLUSIONS: Raltegravir
      penetration into the CSF shows a large interpatient variability, although CSF
      concentrations were above the wild-type IC50 in all patients (and above IC95 in
      28.6%). In this cohort, blood-brain barrier permeability is the only independent
      predictor of raltegravir CPR. The impact of single nucleotide polymorphisms in
      selected genes on raltegravir penetration warrants further studies.

PMID- 23975736
TI  - Mixed treatment comparison of prophylaxis against invasive fungal infections in
      neutropenic patients receiving therapy for haematological malignancies: a
      systematic review.
AB  - OBJECTIVES: Patients receiving therapy for haematological malignancies have a
      higher risk of invasive fungal infections (IFIs). Antifungal prophylaxis is an
      effective strategy against IFIs, but relative effectiveness estimates across
      agents are inconclusive. A mixed treatment comparison (MTC) was conducted to
      estimate the relative effectiveness of all agents for a number of outcomes of
      interest. METHODS: A systematic review was performed to collect evidence from
      randomized controlled trials (RCTs) on the risk of IFIs and on mortality after
      antifungal prophylaxis. The agents analysed were no prophylaxis/placebo,
      fluconazole, itraconazole, micafungin, caspofungin, liposomal amphotericin B and
      posaconazole. Meta-analyses and MTCs were used to synthesize the evidence. The
      primary outcome was the risk of proven or probable IFI. Secondary outcomes were
      risk of candidiasis/aspergillosis, risk of IFI mortality and risk of all-cause
      mortality. RESULTS: Antifungal prophylaxis was more effective than no
      prophylaxis/placebo in reducing IFI risk. The IFI risk after voriconazole or
      posaconazole was lower than after fluconazole [relative risk (RR) 0.38, 95% CI
      0.14-0.83 and RR 0.34, 95% CI 0.14-0.83] or itraconazole tablets (RR 0.22 95% CI
      0.06-0.72 and RR 0.20 95% CI 0.05-0.72). Posaconazole was also found to be more
      effective than no prophylaxis/placebo in reducing all-cause mortality (RR 0.56,
      95% CI 0.30-0.98). Posaconazole had the highest probability of being the most
      effective agent in reducing IFI risk and all-cause mortality. CONCLUSIONS: IFI
      prophylaxis has a positive effect on IFI risk reduction. However, its effect on
      all-cause mortality is not as pronounced. The analysis has additionally
      pinpointed posaconazole as potentially the most effective IFI prophylaxis in
      neutropenic patients.

PMID- 23975738
TI  - Assessment of waist-to-hip ratio attractiveness in women: an anthropometric
      analysis of digital silhouettes.
AB  - The low proportion of waist to hip size in females is a unique and adaptive human
      feature. In contemporary human populations, the waist-to-hip ratio (WHR) is
      negatively associated with women's health, fecundity, and cognitive ability. It
      is, therefore, hypothesized that men will prefer women with low WHR. Although
      this prediction is supported by many studies, considerable disagreement persists
      about which WHR values are the most attractive and the importance of WHR for
      attractiveness of the female body. Unfortunately, the methods applied thus far
      are flawed in several ways. In the present study, we investigated male
      preferences for female WHR using a high precision assessment procedure and
      digitally manufactured, high quality, anthropometrically informed stimuli which
      were disentangled from body mass covariation. Forty men were requested to choose
      the most attractive silhouette consecutively from six series (2 levels of realism
      * 3 levels of body mass), each consisting of 26 female images that varied in WHR
      (from .60 to .85 by .01). Substantial inter-individual variation in the choices
      made was observed. Nevertheless, low and average WHR values were chosen more
      frequently than above-average values or values below the normal variation of the
      trait. This preference pattern mirrors the relationship between WHR and mate
      value, suggesting that the preferences are adaptive.

PMID- 23975739
TI  - Cost effectiveness of moderate to severe psoriasis therapy with etanercept and
      ustekinumab in the United States.
AB  - BACKGROUND: Limited information is available on the cost effectiveness of
      ustekinumab and alternative biologic treatments in a United States (US) setting.
      Given the recent head-to-head clinical trial study of ustekinumab and etanercept,
      an economic model comparing the two treatments can be constructed. Etanercept and
      ustekinumab are indicated for the treatment of chronic moderate to severe plaque
      psoriasis in adult patients who are candidates for phototherapy or systemic
      therapy. OBJECTIVE: Clinical trials have evaluated the efficacy of ustekinumab,
      an anti-cytokine biologic, for the treatment of moderate to severe psoriasis.
      This study evaluated the cost effectiveness of ustekinumab compared with
      etanercept from a US societal perspective. METHODS: A Markov model was
      constructed to simulate the incremental cost per quality-adjusted life-year
      (QALY) gained every 12 weeks over a base-case 3-year time horizon. A hypothetical
      patient cohort was based on the characteristics of the phase III Active
      Comparator Psoriasis Trial (ACCEPT). The main outcome measures were costs and
      QALYs, which were estimated from the US societal perspective. Costs, utilities,
      treatment strategy, and resource use estimates were obtained from relevant
      literature. All costs were adjusted to 2011 US dollars. A 3 % annual discount
      rate was applied to costs and QALYs. Incremental cost-effectiveness ratios were
      in US dollars per QALY gained. RESULTS: For the base-case 3-year time horizon,
      the incremental cost-effectiveness ratio comparing ustekinumab 90 mg with
      etanercept 50 mg was US$384,401 per QALY gained. Ustekinumab 45 mg dominates
      etanercept 50 mg for the same time horizon. These results were robust to
      sensitivity analyses involving treatment strategy, transition probabilities,
      valuing outcomes, and resource use and costs. The probabilistic sensitivity
      analysis suggests ustekinumab 90 mg has a minimal (4 %) chance of being cost
      effective compared with etanercept 50 mg at a willingness-to-pay threshold of
      US$150,000 per QALY improvement. For the same threshold, ustekinumab 45 mg has a
      high (88 %) chance of being cost effective compared with etanercept 50 mg.
      CONCLUSION: Under typical US willingness-to-pay cutoffs, ustekinumab 90 mg is not
      cost effective compared with etanercept 50 mg therapy in moderate to severe
      psoriasis patients for the base-case 3-year time horizon. Ustekinumab 45 mg
      dominates etanercept 50 mg therapy for an equivalent patient psoriasis severity
      and time horizon.

PMID- 23975740
TI  - Impacts of health insurance benefit design on percutaneous coronary intervention
      use and inpatient costs among patients with acute myocardial infarction in
      Shanghai, China.
AB  - BACKGROUND: Currently, the most popular hospital payment method in China is fee
      for-service (FFS) with a global budget cap. As of December 2009, a policy change
      means that heart stents are covered by public health insurance, whereas
      previously they were not. This policy change provides us an opportunity to study
      how a change in insurance benefit affected the quantity and quality of hospital
      services. The new policy introduced incentives for both patients and providers:
      it encourages patient demand for percutaneous coronary intervention (PCI)
      services and stent use (moral hazard effect), and discourages hospital supply due
      to the financial pressures of the global cap (provider gaming effect). If the
      provider's gaming effect dominates the moral hazard effect, actual utilisation
      and costs might go down, and vice versa. Our hypothesis is that patients in the
      higher reimbursement groups will have fewer PCIs and lower inpatient costs.
      OBJECTIVE: We aimed to examine the impact of health insurance benefit design on
      PCI and stent use, and on inpatient costs and out-of-pocket expenses for patients
      with acute myocardial infarction (AMI) in Shanghai. METHODS: We included 720
      patients with AMI (467 before the benefit change and 253 after) from a large
      teaching tertiary hospital in Shanghai. Data were collected via review of
      hospital medical charts, and from the hospital billing database. Patient
      information collected included demographic characteristics, medical history and
      procedure information. All patients were categorised into four groups according
      to their actual reimbursement ratio: high (90-100 %), moderate (80-90 %), low (0
      80 %) and none (self-paid patients). Multiple regression and difference-in
      difference (DID) models were used to investigate the impacts of the health
      insurance benefit design on PCI and stent use, and on total hospital costs and
      patients' out-of-pocket expenses. RESULTS: After the change in insurance benefit
      policy, compared with the self-paid group, PCI rates for the moderate and low
      reimbursement groups increased by 22.2 and 20.3 %, respectively, and decreased by
      48.7 % for the high reimbursement group. The change in insurance benefit policy
      had no impact on the number of stents used. The high reimbursement group had the
      lowest hospital costs, and the low reimbursement group had the highest hospital
      costs, regardless of benefit policy change. The general linear regression results
      showed that the high reimbursement group had higher total hospital costs than the
      self-paid group, but were the lowest among all reimbursement groups after the
      benefit policy change (DIDh = 1,202.21, P = 0.0096). There were no significant
      changes in the other two groups, and there were no differences in the out-of
      pocket costs across any of the insured groups. CONCLUSIONS: Our results suggest
      that the benefit policy change did not impact life-saving procedures or reduce
      patients' burden of disease among AMI patients. The effect of 'provider gaming'
      was the strongest for the high reimbursement group as a result of the global
      budget cap pressure. The current FFS with a global budget cap is of low
      efficiency for cost containment and equity improvement. Payment method reforms
      with alignment of financial incentives to improve provider behaviour in
      practicing evidence-based medicine are needed in China.

PMID- 23975741
TI  - Relationship between agr dysfunction and reduced vancomycin susceptibility in
      methicillin-susceptible Staphylococcus aureus causing bacteraemia.
AB  - OBJECTIVES: Limited data exist regarding the role of agr dysfunction in reducing
      susceptibility to vancomycin in methicillin-susceptible Staphylococcus aureus
      (MSSA). This study investigated the clinical and molecular epidemiology of MSSA
      causing bacteraemia, with emphasis on the reduced susceptibility to vancomycin
      (RSV) phenotype (MIC >= 1.5 mg/L) and its relationship with agr dysfunction.
      METHODS: All MSSA bloodstream isolates obtained at our hospital during 2010 were
      analysed. Antimicrobial susceptibility was determined and time-kill experiments
      were performed for oxacillin. Multilocus sequence type and agr genotype were
      determined and DNA microarray analysis of virulence factors was performed. agr
      dysfunction was assessed phenotypically and by RT-PCR quantification of RNAIII.
      RESULTS: Of 84 MSSA, 55 (65.5%) exhibited the RSV phenotype, comprising 13 clonal
      complexes. agr II polymorphism was more prevalent in RSV than non-RSV isolates
      (41.8% versus 17.2%, P = 0.023) and average levels of RNAIII gene expression were
      higher in RSV than non-RSV isolates (DeltaCt 4.05 +/- 3.29 versus 1.5 +/- 2.11, P
      = 0.005), implying greater agr dysfunction in RSV MSSA. CONCLUSIONS: We
      demonstrated a correlation between RSV phenotype in MSSA and reduced agr
      expression, particularly in association with the agr II genotype. These results
      may help to understand the role of agr dysfunction in the increased mortality in
      MSSA infections.

PMID- 23975742
TI  - Leishmania panamensis infection and antimonial drugs modulate expression of
      macrophage drug transporters and metabolizing enzymes: impact on intracellular
      parasite survival.
AB  - OBJECTIVES: Treatment failure is multifactorial. Despite the importance of host
      cell drug transporters and metabolizing enzymes in the accumulation, distribution
      and metabolism of drugs targeting intracellular pathogens, their impact on the
      efficacy of antileishmanials is unknown. We examined the contribution of
      pharmacologically relevant determinants in human macrophages in the antimony
      mediated killing of intracellular Leishmania panamensis and its relationship with
      the outcome of treatment with meglumine antimoniate. METHODS: Patients with
      cutaneous leishmaniasis who failed (n = 8) or responded (n =8) to treatment were
      recruited. Gene expression profiling of pharmacological determinants in primary
      macrophages was evaluated by quantitative RT-PCR and correlated to the drug
      mediated intracellular parasite killing. Functional validation was conducted
      through short hairpin RNA gene knockdown. RESULTS: Survival of L. panamensis
      after exposure to antimonials was significantly higher in macrophages from
      patients who failed treatment. Sixteen macrophage drug-response genes were
      modulated by infection and exposure to meglumine antimoniate. Correlation
      analyses of gene expression and intracellular parasite survival revealed the
      involvement of host cell metallothionein-2A and ABCB6 in the survival of
      Leishmania during exposure to antimonials. ABCB6 was functionally validated as a
      transporter of antimonial compounds localized in both the cell and phagolysosomal
      membranes of macrophages, revealing a novel mechanism of host cell-mediated
      regulation of intracellular drug exposure and parasite survival within
      phagocytes. CONCLUSIONS: These results provide insight into host cell mechanisms
      regulating the intracellular exposure of Leishmania to antimonials and variations
      among individuals that impact parasite survival. Understanding of host cell
      determinants of intracellular pharmacokinetics/pharmacodynamics opens new avenues
      to improved drug efficacy for intracellular pathogens.

PMID- 23975743
TI  - Methicillin-resistant Staphylococcus aureus carrying the mecC gene: emergence in
      Spain and report of a fatal case of bacteraemia.
AB  - OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) strains carrying
      the mecC gene have been reported from humans and animals from several European
      countries, but never from Spain. We describe the first isolates of mecC-positive
      MRSA of human origin collected in Spain and report a fatal case of bacteraemia.
      METHODS: Isolates were tested for phenotypic resistance using cefoxitin, tested
      for the mecA/mecC genes and toxin genes by PCR, and typed by staphylococcal
      cassette chromosome mec (SCCmec), PFGE, spa, multilocus sequence typing and agr.
      RESULTS: During 2008-13 five MRSA isolates showing resistance to cefoxitin and
      carrying the mecC gene were recovered at one hospital in Spain. In a review of
      5505 S. aureus strains received at the Spanish National Reference Centre for
      Staphylococci from the same period, we found two additional mecC-positive
      isolates. The isolates were recovered from blood (two), wounds (two), joint fluid
      (one), urine (one) and a nasal swab (one). All MRSA were mecA negative, presented
      SCCmecXI, belonged to agr group III and to clonal complex 130, and were negative
      for the production of the toxin genes tst1, eta, etb, etd and Panton-Valentine
      leucocidin. Six isolates belonged to spa type t843 (ST130 and ST1945, where ST
      stands for sequence type) and one to spa type t6220 (ST1945). One patient with
      mecC-positive MRSA sepsis died in the emergency department. CONCLUSIONS: We
      confirm the presence of MRSA carrying the mecC gene in Spain, the ability of this
      livestock-associated MRSA to cause severe infections in humans and the need to
      perform culture-based susceptibility testing methods in order to detect these
      emerging strains.

PMID- 23975744
TI  - The prodromal phase of obesity-related chronic kidney disease: early alterations
      in cardiovascular and renal function in obese children and adolescents.
AB  - Childhood overweight and obesity is a relevant health condition with multi-organ
      involvement. Obesity shows significant tracking into adult life and is associated
      with an increased risk of serious adverse health outcomes both during childhood
      and later adulthood. The classical sequelae of obesity such as hypertension,
      metabolic syndrome and inflammation do develop at a paediatric age.
      Cardiovascular consequences, such as increased carotid intima-media thickness,
      and left ventricular hypertrophy, as well as functional alterations of the heart
      and arteries, are commonly traceable at an early age. Renal involvement can occur
      at a young age and is associated with a high probability of progressive chronic
      kidney disease. There is solid evidence suggesting that consequent treatment
      including both lifestyle changes and pharmacological therapy can reduce
      cardiovascular, metabolic and renal risks in obese children and adolescents. 

PMID- 23975745
TI  - Resistin and all-cause and cardiovascular mortality: effect modification by
      adiponectin in end-stage kidney disease patients.
AB  - BACKGROUND: Resistin is a major adipose tissue cytokine implicated in insulin
      resistance, inflammation and vascular damage. This cytokine is raised in patients
      with end-stage kidney disease (ESKD) but the relationship between resistin and
      major clinical outcomes has not been investigated in this population. METHODS: We
      studied the mutual relationship between resistin and the two major adipokines
      (adiponectin and leptin) and the interaction between resistin and adiponectin
      (ADPN) and all-cause and cardiovascular (CV) mortality in a cohort of 231
      haemodialysis patients followed up for 57 +/- 44 months. RESULTS: Plasma resistin
      was substantially raised in ESKD patients when compared with healthy subjects (P
      < 0.001). On univariate analysis, resistin was related inversely to ADPN (r = 
      0.14, P = 0.04) and directly to C-reactive protein (r = 0.15, P = 0.03), but was
      largely independent of leptin (r = 0.08, P = 0.24) and the HOMA-IR index (r = 
      0.04, P = 0.51). During the follow-up, 165 patients died (96 for CV causes). On
      both univariate (all-cause mortality: P = 0.004; CV mortality P < 0.001) and
      multivariate (all-cause mortality: P = 0.01; CV mortality P < 0.001) Cox
      regression analyses, the effect of resistin on study outcomes was closely
      dependent on ADPN levels. There was a consistent excess risk for all-cause (P =
      0.002) and CV mortality (P = 0.003) by plasma resistin (20 ng/mL) in patients in
      the first ADPN tertile, but no risk excess for these outcomes was apparent in
      patients in the third tertile. CONCLUSION: This study indicates that resistin
      predicts death and fatal CV events depending on plasma ADPN levels. These
      findings underscore the importance of the interaction among adipokines for the
      prediction of adverse clinical outcomes in ESKD.

PMID- 23975746
TI  - Disturbances of Wnt/beta-catenin pathway and energy metabolism in early CKD:
      effect of phosphate binders.
AB  - BACKGROUND: Mineral bone disorder (MBD) is an early complication of chronic
      kidney disease (CKD), with complex interactions in the bone-kidney-energy axis.
      These events lead to impaired bone remodelling, which in turn is associated with
      cardiovascular disease. Recently, we reported on a positive effect of phosphate
      binder treatment on bone remodelling markers and a reduction in serum FGF-23
      levels in predialysis-CKD patients. The goal of the present study of this trial
      was to examine the effects of phosphate binders on energy-regulating hormones and
      Wnt pathway. METHODS: In this present post hoc analysis of the above randomized,
      open-label, 8-week trial, which compared the effects of increasing doses of
      sevelamer-HCl or calcium acetate on various CKD-MBD parameters in 40
      normophosphatemic CKD Stage 3-4 patients, we measured serum sclerostin, Dickkopf
      1, leptin, adiponectin and serotonin concentrations. RESULTS: Serum sclerostin,
      Dickkopf-1 and leptin were elevated at baseline despite normal calcium,
      phosphorus levels and daily urinary phosphorus excretion. There were significant
      and positive correlations between sclerostin and FGF-23, as well between leptin
      and Dickkopf-1. Treatment with both phosphate binders led to a significant
      decrease in phosphate overload. However, sevelamer-HCl, but not with calcium
      acetate, led to a significant decrease in serum FGF-23, sclerostin and leptin,
      and to a significant increase in bone alkaline phosphatase levels. CONCLUSIONS:
      Early stages of CKD are associated with an impairment of the Wnt pathway, as
      reflected by elevated sclerostin, and a dysregulation of energy-regulating
      hormones. Many of these disturbances can be ameliorated by phosphate binder
      treatment, more with sevelamer-HCl than with calcium acetate.

PMID- 23975747
TI  - Simultaneous reversal of risk factors for cardiac death and intensified therapy
      in long-term survivors of paediatric end-stage renal disease over the last 10
      years.
AB  - BACKGROUND: In an extended long-term follow-up of patients on chronic renal
      replacement therapy (RRT) since childhood (LERIC study), we observed a
      substantial reduction in cardiovascular (CV) death over the last decade. In this
      study, we investigated the contemporaneous changes in risk factors for CV death
      and cardioprotective therapy. METHODS: The cohort consisted of 140 Dutch
      patients, who were born before 1979 and started RRT before 15 years of age
      between 1972 and 1992. We compared the prevalence of various factors in 2000 and
      2010 by calculating matched odds ratios (OR(matched)). RESULTS: Median age of
      patients was 38.5 years (range 23.2-50.8) in 2010, after a median time on RRT of
      28 years. The prevalence of CV risk factors decreased from 41.3% in 2000 to 18.8%
      in 2010. The OR(matched) in 2010 compared with 2000 for left ventricular
      hypertrophy, hypertension and hypercholesterolaemia were 0.26 (95% CI 0.09-0.66),
      0.22 (95% CI 0.01-0.59) and 0.04 (95% CI 0.01-0.25), respectively. The rate of
      nonfatal CV events dropped, although not significantly, from 1.75/100 (95% CI 1.3
      2.4) per patient year (py) in 1972-2000 to 0.95/100 (95% CI 0.5-1.7) py in 2000
      2010. ACE inhibitors/angiotensin receptor blockers and cholesterol lowering
      medication were prescribed significantly more often in the period 2000-10
      [OR(matched) = 7.40 (95% CI 2.90-24.10) and 11.5 (95% CI 4.20-43.90)]. Trends
      were similar among those who survived and those who did not survive the last
      decade. CONCLUSIONS: We observed a decrease in clinical CV disease synchronous to
      intensified antihypertensive and antidyslipidaemic therapy in long-term survivors
      of paediatric renal failure. This advocates a vigorous cardioprotective
      management in these patients.

PMID- 23975748
TI  - The CTLA-4 +49GG genotype is associated with susceptibility for nephrotic kidney
      diseases.
AB  - BACKGROUND: The pathogenesis of primary nephrotic kidney diseases is not
      completely understood. As T-cell involvement is suspected, cytotoxic T-lymphocyte
      antigen 4 (CTLA-4) expressed on activated T cells could play a role in the immune
      response. Single-nucleotide polymorphisms (SNPs) in the CTLA-4 gene are
      associated with several autoimmune-related diseases. METHODS: Our goal was to
      study the occurrence of the SNPs -318C/T, +49A/G and CT60 on the CTLA-4 gene in
      healthy blood donors (N = 156) compared with nephrotic patients with biopsy
      proven minimal-change disease (MCD, N = 160), focal segmental glomerulosclerosis
      (FSGS, N = 159) and membranous nephropathy (MN, N = 185). Odds ratios (ORs) with
      95% confidence intervals (95% CIs) were calculated to estimate the strength of
      the association. RESULTS: The +49GG genotype was significantly (P < 0.001)
      associated with the risk for MCD, FSGS and MN (AA versus GG: OR = 3.403, 95% CI =
      1.748-6.622, OR = 3.846, 95% CI = 1.945-7.604 and OR = 2.381, 95% CI = 1.257
      4.511, respectively). No further significant associations, neither with the
      heterozygous genotype of +49A/G nor for the -318C/T or CT60 SNP, were detected.
      CONCLUSIONS: The +49GG genotype of the +49A/G SNP in the CTLA-4 gene is
      associated with the risk for MCD, FSGS and MN, suggesting a possible role for
      CTLA-4 in a proposed common final pathway in the pathogenesis of primary
      nephrotic kidney diseases.

PMID- 23975749
TI  - Patient safety in chronic kidney disease: time for nephrologists to take action.

PMID- 23975750
TI  - Contribution of genetics and epigenetics to progression of kidney fibrosis.
AB  - Chronic kidney disease (CKD) which can lead to end-stage renal failure remains a
      principal challenge in Nephrology. While mechanistic studies provided extensive
      insights into the common pathways of fibrogenesis which underlie the progression
      of CKD, these pre-clinical studies fail to fully explain the vastly different
      progression slopes of individual patients. Recent studies provide evidence that
      genetic polymorphisms and epigenetic variations determine the individual
      susceptibility of patients to develop chronic progressive kidney disease. Here,
      we review recent insights that were provided by genome-wide association studies
      (GWASs), gene-linkage studies and epigenome analysis. The progression of CKD
      towards end-stage renal failure remains a principal unsolved problem in
      Nephrology as effective therapies and predictive tests are still not available [
      1, 2]. Chronic progressive kidney disease is caused by a wide range of diseases,
      with diabetes mellitus, hypertension and primary glomerulopathies being the most
      common causes in the Western world [ 3]. Infections, physical obstruction,
      interstitial nephritides and genetic cystic kidney diseases are also common
      causes of end-stage renal disease (ESRD) [ 3]. Regardless of the primary
      underlying disease, chronically injured kidneys are histomorphologically
      characterized by tubulointerstitial fibrosis [ 1]. In fact, the extent of
      tubulointerstitial fibrosis is the best predictor for kidney survival,
      irrespective of the underlying disease. For this reason, fibrosis is considered
      the common pathway of chronic progressive kidney disease [ 1]. Fibrogenesis is a
      pathological scarring process which involves accumulation of activated
      fibroblasts, excessive deposition of extracellular matrix, failed regeneration of
      tubular epithelium, microvascular rarefaction and (mostly sterile) inflammation [
      4]. Fibrogenesis depends on a complex interaction of the involved cell types
      which is orchestrated by an extensive network of growth factors and signalling
      pathways (which are reviewed extensively elsewhere) [ 1]. In view of the detailed
      mechanistic knowledge of the pathways that orchestrate renal fibrogenesis, it is
      puzzling why progression rates of CKD differ dramatically among patients with
      identical underlying diseases [ 1, 2]. The fibrotic pathways are known, but the
      switches that control their intensities and which determine the speed at which
      fibrosis moves along the progression slope are not yet understood [ 1, 2]. The
      concept that genetic polymorphisms are the basis for individual progression rates
      of CKD is an obvious and attractive one. Distinct susceptibilities of different
      mouse and rat strains to experimental CKD are a strong testament of the impact of
      genetic variations on renal fibrogenesis. Identification of the underlying
      genetic polymorphisms and mechanistic proof of their involvement in the
      progression of CKD, however, is an ongoing challenge. There are two basic
      approaches: one strategy is to perform unbiased screening to identify genes which
      are associated with chronic progressive kidney disease and to then prove their
      mechanistic relevance in experimental studies ('genotype to phenotype approach').
      The second strategy is to selectively analyse polymorphisms of genes which have
      been identified in mechanistic studies as drivers of renal fibrogenesis with
      regard to their association with CKD (phenotype to genotype approach). The
      puzzling observation, however, is that genetic analysis and mechanistic studies
      so far rarely complement each other. The current state of affairs is reviewed in
      more detail below. 

PMID- 23975751
TI  - Screening for albuminuria with subsequent screening for hypertension and
      hypercholesterolaemia identifies subjects in whom treatment is warranted to
      prevent cardiovascular events.
AB  - BACKGROUND: In the general population, many subjects have yet unrecognized
      hypertension and hypercholesterolaemia, and are thus not treated. We investigated
      whether population screening for elevated albuminuria can identify subjects with
      previously unrecognized hypertension and/or hypercholesterolaemia at high risk
      for cardiovascular (CV) disease. METHODS: Included were 8143 subjects (28-75
      years) that participate in the PREVEND study, a general population-based,
      observational cohort study. Elevated albuminuria was defined as an albumin
      concentration >= 20 mg/L in a first morning urine sample confirmed by an albumin
      excretion >= 30 mg/day in two 24-h urine samples. Hypertension was defined as SBP
      >= 140 mmHg or DBP >= 90 mmHg, and hypercholesterolaemia as serum total
      cholesterol >= 6.2 mmol/L, or as HDL cholesterol < 0.9 mmol/L and a total/HDL
      cholesterol ratio of >= 6. Combined CV morbidity and mortality during follow-up
      was adopted as outcome. RESULTS: In the group with, as well as in the group
      without elevated albuminuria, the number of subjects with yet unrecognized
      hypertension and hypercholesterolaemia was at least 2-fold higher than the number
      of subjects known with these CV risk factors. Mean follow-up was 7.1 +/- 1.5
      years, during which 445 CV events occurred. The hazard ratio for CV events was
      significantly elevated in the subjects with, compared with those without elevated
      albuminuria, independent of whether they had no CV risk factor present, a CV risk
      factor known or a CV risk factor newly discovered. The CV event rate in those
      with an elevated albuminuria crossed the recommended threshold to start
      antihypertensive or anticholesterolaemic treatment, not only when the CV risk
      factor was known, but also in the subgroup with newly diagnosed CV risk factor.
      In subjects with a newly discovered CV risk factor without albuminuria, absolute
      CV risk was significantly lower. CONCLUSIONS: Screening for elevated albuminuria
      and subsequent screening for CV risk factors identify subjects with yet unknown
      CV risk factors at high risk for CV disease that are likely to benefit from early
      preventive treatment.

PMID- 23975752
TI  - Underweight, overweight and obesity in paediatric dialysis and renal transplant
      patients.
AB  - BACKGROUND: The prevalence of childhood overweight is rising worldwide, but in
      children on renal replacement therapy (RRT) a poor nutritional status is still
      the primary concern. We aimed to study the prevalence of, and factors associated
      with, underweight and overweight/obesity in the European paediatric RRT
      population. Moreover, we assessed the evolution of body mass index (BMI) after
      the start of RRT. METHODS: We included 4474 patients younger than 16 years from
      25 countries of whom BMI data, obtained between 1995 and 2010, were available
      within the European Society for Paediatric Nephrology/European Renal Association
      European Dialysis and Transplant Association Registry. Prevalence estimates for
      under- and overweight/obesity were calculated using age and sex-specific criteria
      of the World Health Organization (WHO, 0-1 year olds) and the International
      Obesity Task Force cut-offs (2-15 year olds). RESULTS: The prevalence of
      underweight was 3.5%, whereas 20.8% of the patients were overweight and 12.5%
      obese. Factors associated with being underweight were receiving dialysis
      treatment and infant age. Among transplanted recipients, a very short stature
      (OR: 1.64, 95% CI: 1.40-1.92) and glucocorticoid treatment (OR: 1.23, 95% CI:
      1.03-1.47) were associated with a higher risk of being overweight/obese. BMI
      increased post-transplant, and a lower BMI and a higher age at the start of RRT
      were associated with greater BMI changes during RRT treatment. CONCLUSIONS:
      Overweight and obesity, rather than underweight, are highly prevalent in European
      children on RRT. Short stature among graft recipients had a strong association
      with overweight, while underweight appears to be only a problem in infants. Our
      findings suggest that nutritional management in children receiving RRT should
      focus as much on the prevention and treatment of overweight as on preventing
      malnutrition.

PMID- 23975753
TI  - Myofibroblasts, regeneration or renal fibrosis--is there a decisive hint?
AB  - Activated fibroblasts, denoted as myofibroblasts, express smooth muscle actin
      (SMA) and are considered key mediators of renal fibrosis. To identify and isolate
      these elusive cells, LeBleu et al. generated a new transgenic mouse model
      expressing a red fluorescent protein under the control of the alpha SMA promoter.
      Gene expression profiling from cultured myofibroblasts identified human
      epididymis protein 4 [HE4, also denoted whey acidic protein (WAP) four-disulphide
      core domain 2] as the most upregulated gene. Since the WAP domains are implicated
      in protease inhibition, the authors demonstrate the ability of recombinant HE4 to
      bind and inhibit a number of known proteases. To demonstrate an involvement of
      HE4 in disease pathology, the authors next showed that the neutralization of HE4
      alleviates kidney fibrosis in murine disease models, i.e. 5/6 nephrectomy,
      unilateral ureteral obstruction and nephrotoxic serum-induced nephritis. Finally,
      they went on to verify the enhanced expression of HE4 in human fibrosis
      associated fibroblasts in comparison to normal fibroblasts as well as in serum
      samples of patients with chronic kidney diseases. Thus, they conclude that HE4
      can serve as a biomarker as well as a therapeutic target for the treatment of
      renal fibrosis. 

PMID- 23975754
TI  - Identification and characterization of interactions between abscisic acid and
      human heat shock protein 70 family members.
AB  - Abscisic acid (ABA) is a stress-inducible plant hormone comprising an inevitable
      component of the human diet. Recently, stress-induced accumulation of autocrine
      ABA was shown in humans, as well as ABA-mediated modulation of a number of
      disease-associated systems. Now, the application of a chemical proteomics
      approach to gain further insight into ABA mechanisms of action in mammalian cells
      is reported. An ABA mimetic photoaffinity probe was applied to intact mammalian
      insulinoma and embryonic cells, leading to the identification of heat shock
      protein 70 (HSP70) family members, (including GRP78 and HSP70-2) as putative
      human ABA-binding proteins. In vitro characterization of the ABA-HSP70
      interactions yielded K(d)s in the 20-60 uM range, which decreased several fold in
      the presence of co-chaperone. However, ABA was found to have only variable- and
      co-chaperone-independent effects on the ATPase activity of these proteins. The
      potential implications of these ABA-HSP70 interactions are discussed with respect
      to the intracellular protein folding and extracellular receptor-like activities
      of these stress-inducible proteins. While mechanistic and functional relevance
      remain enigmatic, we conclude that ABA can bind to human HSP70 family members
      with physiologically relevant affinities and in a co-chaperone-dependent manner.

PMID- 23975755
TI  - Impact of supplemental immunisation activity (SIA) campaigns on health systems:
      findings from South Africa.
AB  - BACKGROUND: Supplemental immunisation activity (SIA) campaigns provide children
      with an additional dose of measles vaccine and deliver other child health
      interventions including vitamin A supplements, deworming medications and oral
      polio vaccines. They also require the mobilisation of a large health workforce.
      We assess the impact of the implementation of SIA campaigns on selected routine
      child and maternal health services in South Africa (SA). METHODS: We use district
      level monthly headcount data for 52 South African districts for the period 2001
      2010, sourced from the District Health Information System, SA. The data include
      12 child and maternal health headcount indicators including routine immunisation,
      and maternal and reproductive health indicators. We analyse the association
      between the implementation of the 2010 SIA campaign and the change
      (decrease/increase) in headcounts, using a linear regression model. RESULTS: We
      find a significant decrease for eight indicators. The total number of fully
      immunised children before age 1 decreased by 29% (95% CI 23% to 35%, p<0.001)
      during the month of SIA implementation; contraceptive use and antenatal visits
      decreased by 7-17% (p <= 0.02) and about 10% (p<0.001), respectively.
      CONCLUSIONS: SIA campaigns may negatively impact health systems during the period
      of implementation by disrupting regular functioning and diverting resources from
      other activities, including routine child and maternal health services. SIA
      campaigns present multidimensional costs that need to be explicitly considered in
      benefit-cost assessments.

PMID- 23975757
TI  - Surveying clinicians: an introduction to the special issue.

PMID- 23975756
TI  - Therapeutic PD-1 pathway blockade augments with other modalities of immunotherapy
      T-cell function to prevent immune decline in ovarian cancer.
AB  - The tumor microenvironment mediates induction of the immunosuppressive programmed
      cell death-1 (PD-1) pathway, and targeted interventions against this pathway can
      help restore antitumor immunity. To gain insight into these responses, we studied
      the interaction between PD-1 expressed on T cells and its ligands (PD-1:PD-L1, PD
      1:PD-L2, and PD-L1:B7.1), expressed on other cells in the tumor microenvironment,
      using a syngeneic orthotopic mouse model of epithelial ovarian cancer (ID8).
      Exhaustion of tumor-infiltrating lymphocytes (TIL) correlated with expression of
      PD-1 ligands by tumor cells and tumor-derived myeloid cells, including tumor
      associated macrophages (TAM), dendritic cells, and myeloid-derived suppressor
      cells (MDSC). When combined with GVAX or FVAX vaccination (consisting of
      irradiated ID8 cells expressing granulocyte macrophage colony-stimulating factor
      or FLT3 ligand) and costimulation by agonistic alpha-4-1BB or TLR 9 ligand,
      antibody-mediated blockade of PD-1 or PD-L1 triggered rejection of ID8 tumors in
      75% of tumor-bearing mice. This therapeutic effect was associated with increased
      proliferation and function of tumor antigen-specific effector CD8(+) T cells,
      inhibition of suppressive regulatory T cells (Treg) and MDSC, upregulation of
      effector T-cell signaling molecules, and generation of T memory precursor cells.
      Overall, PD-1/PD-L1 blockade enhanced the amplitude of tumor immunity by
      reprogramming suppressive and stimulatory signals that yielded more powerful
      cancer control.

PMID- 23975758
TI  - Facilitators and barriers to survey participation by physicians: a call to action
      for researchers.
AB  - Surveys of health care providers are a well-established tool for obtaining
      information about the organization and delivery of care as well as about provider
      knowledge and attitudes. However, declining response rates to provider surveys
      are a widely acknowledged concern. Although a number of studies have identified
      specific methods for increasing response rates in health care provider-and
      particularly physician-surveys, few have addressed the more fundamental question
      of what motivates or deters providers from survey participation. We briefly
      review theoretical perspectives concerning why providers choose to participate in
      surveys, and what is known about facilitators and barriers to participation. We
      then describe several research designs (i.e., focus groups, key informant
      interviews, diary and office workflow studies, surveying the surveyors, and
      follow-back studies of respondents/nonrespondents) for obtaining empirical data
      on facilitators and barriers to survey participation, particularly by physicians
      and medical groups. Researchers must begin to build an evidence base for
      understanding provider decisions concerning survey participation. 

PMID- 23975759
TI  - Sample frame and related sample design issues for surveys of physicians and
      physician practices.
AB  - A sample frame is the listing of the units from which a sample is to be selected.
      When deciding upon a file to serve as a source for a sample frame for a survey,
      perhaps the most important consideration is the extent to which the target
      population will be covered by the frame. However, other issues also come into
      play such as the accuracy of contact and other information appearing on the file
      as well as its cost. The American Medical Association Masterfile has long been
      considered the preferred choice for surveys of physicians, although it does have
      drawbacks. Here we consider two alternative files, discussing their relative
      advantages and disadvantages. For surveys of physician practices (or other
      organizations that employ physicians), there have been no files that are obvious
      choices to serve as the basis for a sample frame. Here we discuss data collection
      on physician practices from an analytic perspective and consider how sampling
      physicians to obtain practice level data may be a desirable approach. 

PMID- 23975760
TI  - Surveying clinicians by web: current issues in design and administration.
AB  - The versatility, speed, and reduced costs with which web surveys can be conducted
      with clinicians are often offset by low response rates. Drawing on best practices
      and general recommendations in the literature, we provide an evidence-based
      overview of methods for conducting online surveys with providers. We highlight
      important advantages and disadvantages of conducting provider surveys online and
      include a review of differences in response rates between web and mail surveys of
      clinicians. When administered online, design-based features affect rates of
      survey participation and data quality. We examine features likely to have an
      impact including sample frames, incentives, contacts (type, timing, and content),
      mixed-mode approaches, and questionnaire length. We make several recommendations
      regarding optimal web-based designs, but more empirical research is needed,
      particularly with regard to identifying which combinations of incentive and
      contact approaches yield the highest response rates and are the most cost
      effective. 

PMID- 23975761
TI  - Enhancing surveys of health care professionals: a meta-analysis of techniques to
      improve response.
AB  - Surveys involving health care providers are characterized by low and declining
      response rates (RRs), and researchers have utilized various strategies to
      increase survey RRs among health professionals. Based on 48 studies with 156
      subgroups of within-study conditions, a multilevel meta-regression analysis was
      conducted to summarize the effects of different strategies employed in surveys of
      health professionals. An estimated overall survey RR among health professionals
      was 0.53 with a significant downward trend during the last half century. Of the
      variables that were examined, mode of data collection, incentives, and number of
      follow-up attempts were all found to be significantly related to RR. The mail
      survey mode was more effective in improving RR, compared to the online or web
      survey mode. Relative to the non-incentive subgroups, subgroups receiving
      monetary incentives were more likely to respond, while nonmonetary incentive
      groups were not significantly different from non-incentive groups. When number of
      follow-ups was considered, the one or two attempts of follow-up were found to be
      effective in increasing survey RR among health professionals. Having noted
      challenges associated with surveying health professionals, researchers must make
      every effort to improve access to their target population by implementing
      appropriate incentive- and design-based strategies demonstrated to improve
      participation rates. 

PMID- 23975762
TI  - Protein-ligand binding site recognition using complementary binding-specific
      substructure comparison and sequence profile alignment.
AB  - MOTIVATION: Identification of protein-ligand binding sites is critical to protein
      function annotation and drug discovery. However, there is no method that could
      generate optimal binding site prediction for different protein types. Combination
      of complementary predictions is probably the most reliable solution to the
      problem. RESULTS: We develop two new methods, one based on binding-specific
      substructure comparison (TM-SITE) and another on sequence profile alignment (S
      SITE), for complementary binding site predictions. The methods are tested on a
      set of 500 non-redundant proteins harboring 814 natural, drug-like and metal ion
      molecules. Starting from low-resolution protein structure predictions, the
      methods successfully recognize >51% of binding residues with average Matthews
      correlation coefficient (MCC) significantly higher (with P-value <10(-9) in
      student t-test) than other state-of-the-art methods, including COFACTOR, FINDSITE
      and ConCavity. When combining TM-SITE and S-SITE with other structure-based
      programs, a consensus approach (COACH) can increase MCC by 15% over the best
      individual predictions. COACH was examined in the recent community-wide COMEO
      experiment and consistently ranked as the best method in last 22 individual
      datasets with the Area Under the Curve score 22.5% higher than the second best
      method. These data demonstrate a new robust approach to protein-ligand binding
      site recognition, which is ready for genome-wide structure-based function
      annotations. AVAILABILITY: http://zhanglab.ccmb.med.umich.edu/COACH/

PMID- 23975763
TI  - RNAfbinv: an interactive Java application for fragment-based design of RNA
      sequences.
AB  - SUMMARY: In RNA design problems, it is plausible to assume that the user would be
      interested in preserving a particular RNA secondary structure motif, or fragment,
      for biological reasons. The preservation could be in structure or sequence, or
      both. Thus, the inverse RNA folding problem could benefit from considering
      fragment constraints. We have developed a new interactive Java application called
      RNA fragment-based inverse that allows users to insert an RNA secondary structure
      in dot-bracket notation. It then performs sequence design that conforms to the
      shape of the input secondary structure, the specified thermodynamic stability,
      the specified mutational robustness and the user-selected fragment after shape
      decomposition. In this shape-based design approach, specific RNA structural
      motifs with known biological functions are strictly enforced, while others can
      possess more flexibility in their structure in favor of preserving physical
      attributes and additional constraints. AVAILABILITY: RNAfbinv is freely available
      for download on the web at http://www.cs.bgu.ac.il/~RNAexinv/RNAfbinv. The site
      contains a help file with an explanation regarding the exact use.

PMID- 23975764
TI  - NextGenMap: fast and accurate read mapping in highly polymorphic genomes.
AB  - SUMMARY: When choosing a read mapper, one faces the trade off between speed and
      the ability to map reads in highly polymorphic regions. Here, we report
      NextGenMap, a fast and accurate read mapper, which reduces this dilemma.
      NextGenMap aligns reads reliably to a reference genome even when the sequence
      difference between target and reference genome is large, i.e. highly polymorphic
      genome. At the same time, NextGenMap outperforms current mapping methods with
      respect to runtime and to the number of correctly mapped reads. NextGenMap
      efficiently uses the available hardware by exploiting multi-core CPUs as well as
      graphic cards (GPUs), if available. In addition, NextGenMap handles automatically
      any read data independent of read length and sequencing technology. AVAILABILITY:
      NextGenMap source code and documentation are available at:
      http://cibiv.github.io/NextGenMap/. CONTACT: fritz.sedlazeck@univie.ac.at.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 23975765
TI  - GIM3E: condition-specific models of cellular metabolism developed from
      metabolomics and expression data.
AB  - MOTIVATION: Genome-scale metabolic models have been used extensively to
      investigate alterations in cellular metabolism. The accuracy of these models to
      represent cellular metabolism in specific conditions has been improved by
      constraining the model with omics data sources. However, few practical methods
      for integrating metabolomics data with other omics data sources into genome-scale
      models of metabolism have been developed. RESULTS: GIM(3)E (Gene Inactivation
      Moderated by Metabolism, Metabolomics and Expression) is an algorithm that
      enables the development of condition-specific models based on an objective
      function, transcriptomics and cellular metabolomics data. GIM(3)E establishes
      metabolite use requirements with metabolomics data, uses model-paired
      transcriptomics data to find experimentally supported solutions and provides
      calculations of the turnover (production/consumption) flux of metabolites.
      GIM(3)E was used to investigate the effects of integrating additional omics
      datasets to create increasingly constrained solution spaces of Salmonella
      Typhimurium metabolism during growth in both rich and virulence media. This
      integration proved to be informative and resulted in a requirement of additional
      active reactions (12 in each case) or metabolites (26 or 29, respectively). The
      addition of constraints from transcriptomics also impacted the allowed solution
      space, and the cellular metabolites with turnover fluxes that were necessarily
      altered by the change in conditions increased from 118 to 271 of 1397.
      AVAILABILITY: GIM(3)E has been implemented in Python and requires a COBRApy
      0.2.x. The algorithm and sample data described here are freely available at:
      http://opencobra.sourceforge.net/ CONTACTS: brianjamesschmidt@gmail.com

PMID- 23975766
TI  - RNA secondary structure diagrams for very large molecules: RNAfdl.
AB  - SUMMARY: There are many programs that can read the secondary structure of an RNA
      molecule and draw a diagram, but hardly any that can cope with 10(3) bases.
      RNAfdl is slow but capable of producing intersection-free diagrams for ribosome
      sized structures, has a graphical user interface for adjustments and produces
      output in common formats. AVAILABILITY AND IMPLEMENTATION: Source code is
      available under the GNU General Public License v3.0 at
      http://sourceforge.net/projects/rnafdl for Linux and similar systems or Windows
      using MinGW. RNAfdl is implemented in C, uses the Cairo 2D graphics library and
      offers both command line and graphical user interfaces. CONTACT: hecker@rth.dk

PMID- 23975767
TI  - catRAPID omics: a web server for large-scale prediction of protein-RNA
      interactions.
AB  - SUMMARY: Here we introduce catRAPID omics, a server for large-scale calculations
      of protein-RNA interactions. Our web server allows (i) predictions at proteomic
      and transcriptomic level; (ii) use of protein and RNA sequences without size
      restriction; (iii) analysis of nucleic acid binding regions in proteins; and (iv)
      detection of RNA motifs involved in protein recognition. RESULTS: We developed a
      web server to allow fast calculation of ribonucleoprotein associations in
      Caenorhabditis elegans, Danio rerio, Drosophila melanogaster, Homo sapiens, Mus
      musculus, Rattus norvegicus, Saccharomyces cerevisiae and Xenopus tropicalis
      (custom libraries can be also generated). The catRAPID omics was benchmarked on
      the recently published RNA interactomes of Serine/arginine-rich splicing factor 1
      (SRSF1), Histone-lysine N-methyltransferase EZH2 (EZH2), TAR DNA-binding protein
      43 (TDP43) and RNA-binding protein FUS (FUS) as well as on the protein
      interactomes of U1/U2 small nucleolar RNAs, X inactive specific transcript (Xist)
      repeat A region (RepA) and Crumbs homolog 3 (CRB3) 3'-untranslated region RNAs.
      Our predictions are highly significant (P < 0.05) and will help the
      experimentalist to identify candidates for further validation. AVAILABILITY:
      catRAPID omics can be freely accessed on the Web at
      http://s.tartaglialab.com/catrapid/omics. Documentation, tutorial and FAQs are
      available at http://s.tartaglialab.com/page/catrapid_group.

PMID- 23975768
TI  - GOLVEN peptides as important regulatory signalling molecules of plant
      development.
AB  - The contribution of signalling peptides to plant development is increasingly
      evident as more new peptide families become identified. The recently discovered
      GLV/RGF/CLEL secreted peptide family comprises 11 members in Arabidopsis and has
      been shown by independent research groups to be involved in different plant
      developmental programmes such as root meristem maintenance, root hair
      development, and root and hypocotyl gravitropism. This short review summarizes
      our current knowledge on GLV/RGF/CLEL peptides and highlights future challenges
      to decipher their function. 

PMID- 23975769
TI  - Use of thiol-disulfide exchange method to study transmembrane peptide association
      in membrane environments.
AB  - The development of methods for reversibly folding membrane proteins in a two
      state manner remains a considerable challenge for studies of membrane protein
      stability. In recent years, a variety of techniques have been established and
      studies of membrane protein folding thermodynamics in the native bilayer
      environments have become feasible. Here we present the thiol-disulfide exchange
      method, a promising experimental approach for investigating the thermodynamics of
      transmembrane (TM) helix-helix association in membrane-mimicking environments.
      The method involves initiating disulfide cross-linking of a protein under
      reversible redox conditions in a thiol-disulfide buffer and quantitative
      assessment of the extent of cross-linking at equilibrium. This experimental
      method provides a broadly applicable tool for thermodynamic studies of folding,
      oligomerization, and helix-helix interactions of membrane proteins. 

PMID- 23975770
TI  - Measurement of transmembrane peptide interactions in liposomes using Forster
      resonance energy transfer (FRET).
AB  - Present day understanding of the thermodynamic properties of integral membrane
      proteins (IMPs) lags behind that of water-soluble proteins due to difficulties in
      mimicking the physiological environment of the IMPs in order to obtain a
      reversible folded system. Despite such challenges faced in studying these
      systems, significant progress has been made in the study of the oligomerization
      of single span transmembrane helices. One of the primary methods available to
      characterize these systems is based on Forster resonance energy transfer (FRET).
      FRET is a widely used spectroscopic tool that provides proximity data that can be
      fitted to obtain the energetics of a system. Here we discuss various technical
      aspects related to the application of FRET to study transmembrane peptide
      oligomerization in liposomes. The analysis is based on FRET efficiency relative
      to the concentration of the peptides in the bilayer (peptide:lipid ratio). Some
      important parameters that will be discussed include labeling efficiency, sample
      homogeneity, and equilibration. Furthermore, data analysis has to be performed
      keeping in mind random colocalization of donors and acceptors in liposome
      vesicles.

PMID- 23975772
TI  - Genetic systems for monitoring interactions of transmembrane domains in bacterial
      membranes.
AB  - In recent years several systems have been developed to study interactions of TM
      domains within the inner membrane of the Gram-negative bacterium Escherichia
      coli. Mostly, a transmembrane domain of interest is fused to a soluble DNA
      binding domain, which dimerizes in E. coli cytoplasm after interactions of the
      transmembrane domains. The dimeric DNA-binding domain subsequently binds to a
      promoter/operator region and thereby activates or represses a reporter gene. In
      1996 the first bacterial system has been introduced to measure interactions of TM
      helices within a bacterial membrane, which is based on fusion of a transmembrane
      helix of interest to the DNA-binding domain of the Vibrio cholerae ToxR protein.
      Interaction of a transmembrane helix of interest within the membrane environment
      results in dimerization of the DNA-binding domain in the bacterial cytoplasm, and
      the dimeric DNA-binding domain then binds to the DNA and activates a reporter
      gene. Subsequently, systems with improved features, such as the TOXCAT- or
      POSSYCCAT system, which allow screening of TM domain libraries, or the GALLEX
      system, which allows measuring heterotypic interactions of TM helices, have been
      developed and successfully applied. Here we briefly introduce the currently most
      applied systems and discuss their advantages together with their limitations.

PMID- 23975771
TI  - Measuring transmembrane helix interaction strengths in lipid bilayers using
      steric trapping.
AB  - We have developed a method to measure strong transmembrane (TM) helix interaction
      affinities in lipid bilayers that are difficult to measure by traditional
      dilution methods. The method, called steric trapping, couples dissociation of
      biotinylated TM helices to a competitive binding by monovalent streptavidin
      (mSA), so that dissociation is driven by the affinity of mSA for biotin and mSA
      concentration. By adjusting the binding affinity of mSA through mutation, the
      method can obtain dissociation constants of TM helix dimers (K d,dimer) over a
      range of six orders of magnitudes. The K d,dimer limit of measurable target
      interaction is extended 3-4 orders of magnitude lower than possible by dilution
      methods. Thus, steric trapping opens up new opportunities to study the folding
      and assembly of alpha-helical membrane proteins in lipid bilayer environments.
      Here we provide detailed methods for applying steric trapping to a TM helix
      dimer. 

PMID- 23975773
TI  - Analyzing the effects of hydrophobic mismatch on transmembrane alpha-helices
      using tryptophan fluorescence spectroscopy.
AB  - Hydrophobic matching between transmembrane protein segments and the lipid bilayer
      in which they are embedded is a significant factor in the behavior and
      orientation of such transmembrane segments. The condition of hydrophobic mismatch
      occurs when the hydrophobic thickness of a lipid bilayer is significantly
      different than the length of the membrane spanning segment of a protein,
      resulting in a mismatch. This mismatch can result in altered function of proteins
      as well as nonnative structural arrangements including effects on transmembrane
      alpha-helix tilt angles, oligomerization state, and/or the formation of non
      transmembrane topographies. Here, a fluorescence-based protocol is described for
      testing model transmembrane alpha-helices and their sensitivity to hydrophobic
      mismatch by measuring the propensity of these helices to form non-transmembrane
      structures. Overall, good hydrophobic matching between the bilayer and
      transmembrane segments is an important factor that must be considered when
      designing membrane proteins or peptides.

PMID- 23975774
TI  - Folding alpha-helical membrane proteins into liposomes in vitro and determination
      of secondary structure.
AB  - The native environment of integral membrane proteins is a highly complex lipid
      bilayer composed of many different types of lipids, the physical characteristics
      of which can profoundly influence protein stability, folding, and function.
      Secondary transporters are a class of protein where changes to both structure and
      activity have been observed in different bilayer environments. In order to study
      these interactions in vitro, it is necessary to extract and purify the protein
      and exchange it into an artificial lipid system that can be manipulated to
      control protein behavior. Liposomes are a commonly used model system that is
      particularly suitable for studying transporters. GalP and LacY can be
      reconstituted or refolded into vesicles with a high degree of efficiency for
      further structural analysis. Circular dichroism spectroscopy is an important
      technique in monitoring protein folding, which allows the decomposition of
      spectra into secondary structural components. 

PMID- 23975775
TI  - Solvation models and computational prediction of orientations of peptides and
      proteins in membranes.
AB  - Membrane-associated peptides and proteins function in the highly heterogeneous
      environment of the lipid bilayer whose physico-chemical properties change non
      monotonically along the bilayer normal. To simulate insertion of peptides and
      proteins into membranes and correctly reproduce the energetics of this process,
      an adequate solvation model and physically realistic representation of the lipid
      bilayer should be employed. We present a brief overview of the existing solvation
      models and their application for prediction of binding affinities and
      orientations of proteins in membranes. Particular emphasis is placed on the
      recently proposed PPM method, the corresponding web server, and the OPM database
      that were designed for positioning in membranes of integral and peripheral
      proteins with known three-dimensional structures.

PMID- 23975778
TI  - Prediction and design of outer membrane protein-protein interactions.
AB  - Protein-protein interactions (PPI) play central roles in biological processes,
      motivating us to understand the structural basis underlying affinity and
      specificity. In this chapter, we focus on biochemical and computational design
      strategies of assessing and detecting PPIs of beta-barrel outer membrane proteins
      (OMPs). A few case studies are presented highlighting biochemical techniques used
      to dissect the energetics of oligomerization and determine amino acids forming
      the key interactions of the PPI sites. Current computational strategies for
      detecting/predicting PPIs are introduced, and examples of computational and
      rational engineering strategies applied to OMPs are presented.

PMID- 23975776
TI  - Membrane protein structure determination: back to the membrane.
AB  - NMR spectroscopy enables the structures of membrane proteins to be determined in
      the native-like environment of the phospholipid bilayer membrane. This chapter
      outlines the methods for membrane protein structural studies using solid-state
      NMR spectroscopy with samples of membrane proteins incorporated in
      proteoliposomes or planar lipid bilayers. The methods for protein expression and
      purification, sample preparation, and NMR experiments are described and
      illustrated with examples from OmpX and Ail, two bacterial outer membrane
      proteins that function in bacterial virulence.

PMID- 23975779
TI  - Design of transmembrane peptides: coping with sticky situations.
AB  - Membrane proteins have central roles in cellular processes ranging from nutrient
      uptake to cell-cell communication, and are key drug targets. However, research on
      alpha-helical integral membrane proteins is in its relative infancy vs. water
      soluble proteins, largely because of their water insolubility when extracted from
      their native membrane environment. Peptides with sequences that correspond to the
      membrane-spanning segments of alpha-helical integral membrane proteins, termed
      transmembrane (TM) peptides, provide valuable tools for the characterization of
      these molecules. Here we describe in detail protocols for the design of TM
      peptides from the sequences of natural alpha-helical integral membrane proteins
      and outline strategies for their synthesis and for improving their solubility
      properties. 

PMID- 23975780
TI  - Engineering and utilization of reporter cell lines for cell-based assays of
      transmembrane receptors.
AB  - Transmembrane receptors, a subset of integral membrane proteins, are the
      receivers that transduce an extracellular chemical message into an intracellular
      response. Accordingly, these proteins are of particular interest in the
      scientific community and are probably best studied as part of a cellular system.
      Herein, we detail the engineering of a fluorescent and bioluminescent reporter
      cell line for a transmembrane receptor and how to employ it in a directed
      evolution screen that identifies peptide regulators of receptor activity. 

PMID- 23975781
TI  - Fluorination in the design of membrane protein assemblies.
AB  - Protein design approaches based on the binary patterning of nonpolar and polar
      amino acids have been successful in generating native-like protein structures of
      amphiphilic alpha-helices or idealized amphiphilic beta-strands in aqueous
      solution. Such patterning is not possible in the nonpolar environment of
      biological membranes, precluding the application of conventional approaches to
      the design of membrane proteins that assemble into discrete aggregates. This
      review surveys a promising, new strategy for membrane protein design that
      exploits the unique properties of fluorocarbons-in particular, their ability to
      phase separate from both water (due to their hydrophobicity) and hydrocarbons
      (due to their lipophobicity)-to generate membrane protein assemblies. The ability
      to design such discrete assemblies should enable the disruption of protein
      protein interactions and provide templates for novel biomaterials and
      therapeutics.

PMID- 23975777
TI  - On the role of NMR spectroscopy for characterization of antimicrobial peptides.
AB  - Antimicrobial peptides (AMPs) provide a primordial source of immunity, conferring
      upon eukaryotic cells resistance against bacteria, protozoa, and viruses. Despite
      a few examples of anionic peptides, AMPs are usually relatively short positively
      charged polypeptides, consisting of a dozen to about a hundred amino acids, and
      exhibiting amphipathic character. Despite significant differences in their
      primary and secondary structures, all AMPs discovered to date share the ability
      to interact with cellular membranes, thereby affecting bilayer stability,
      disrupting membrane organization, and/or forming well-defined pores. AMPs
      selectively target infectious agents without being susceptible to any of the
      common pathways by which these acquire resistance, thereby making AMPs prime
      candidates to provide therapeutic alternatives to conventional drugs. However,
      the mechanisms of AMP actions are still a matter of intense debate. The structure
      function paradigm suggests that a better understanding of how AMPs elicit their
      biological functions could result from atomic resolution studies of peptide-lipid
      interactions. In contrast, more strict thermodynamic views preclude any roles for
      three-dimensional structures. Indeed, the design of selective AMPs based solely
      on structural parameters has been challenging. In this chapter, we will focus on
      selected AMPs for which studies on the corresponding AMP-lipid interactions have
      helped reach an understanding of how AMP effects are mediated. We will emphasize
      the roles of both liquid- and solid-state NMR spectroscopy for elucidating the
      mechanisms of action of AMPs. 

PMID- 23975782
TI  - A brief introduction to tiling microarrays: principles, concepts, and
      applications.
AB  - Technological achievements have always contributed to the advancement of
      biomedical research. It has never been more so than in recent times, when the
      development and application of innovative cutting-edge technologies have
      transformed biology into a data-rich quantitative science. This stunning
      revolution in biology primarily ensued from the emergence of microarrays over two
      decades ago. The completion of whole-genome sequencing projects and the advance
      in microarray manufacturing technologies enabled the development of tiling
      microarrays, which gave unprecedented genomic coverage. Since their first
      description, several types of application of tiling arrays have emerged, each
      aiming to tackle a different biological problem. Although numerous algorithms
      have already been developed to analyze microarray data, new method development is
      still needed not only for better performance but also for integration of
      available microarray data sets, which without doubt constitute one of the largest
      collections of biological data ever generated. In this chapter we first introduce
      the principles behind the emergence and the development of tiling microarrays,
      and then discuss with some examples how they are used to investigate different
      biological problems. 

PMID- 23975783
TI  - Design of tiling arrays and their application to bacterial transcriptome
      analysis.
AB  - Whole-genome sequencing and annotation have clarified total gene number and
      structure in a variety of organisms. Microarrays have facilitated transcriptome
      analysis through the use of probes that target a large number of genes based on
      genomic information. However, microarrays are limited in that they can only
      examine known or predicted genes; non-annotated genes and noncoding regions
      cannot be accounted for.Recent advances in technology have led to the design of
      tiling arrays, which contain a vastly increased number of spotted probes, and at
      higher density. Tiling arrays cover the entire genome of a prokaryotic species in
      an unbiased fashion by designing a large number of probes. Upon hybridization of
      total RNA, all the transcribed regions of the genome, irrespective of gene
      annotation, can be detected. As opposed to next-generation sequencing, tiling
      arrays are cost-effective, easy to analyze, and have been used for experiments as
      diverse as transcriptome analysis, ChIP-chip, and DNA sequence variation
      detection. In this chapter, the methods for bacterial tiling array slide design,
      RNA sample preparation, hybridization, and data analysis are described. 

PMID- 23975784
TI  - Transcript profiling in Arabidopsis with genome tiling microarrays.
AB  - Microarray technology is at present a standardized workflow for genome-wide
      expression analysis. Whole-genome tiling microarrays have emerged as an important
      platform for flexible and comprehensive expression profiling. In this chapter we
      describe a detailed standardized workflow for experiments assessing the
      transcriptome of Arabidopsis using tiling arrays and provide useful hints for
      critical steps from experimental design to data analysis. Although the protocol
      is optimized for AGRONOMICS1 arrays, it can readily be adapted to other tiling
      arrays. AGRONOMICS1 is the first platform that enables strand-specific expression
      analysis of the Arabidopsis genome with a single array. Moreover, it includes all
      perfect match probes from the original ATH1 array, allowing readily integration
      with the large existing ATH1 knowledge base. This workflow is designed for the
      analysis of raw data for any number of samples and it does not pose any
      particular hardware requirements.

PMID- 23975785
TI  - Genome-wide analysis of transcription factor-binding sites in skeletal muscle
      cells using ChIP-seq.
AB  - Transcriptional regulation of gene expression constitutes a fundamental mechanism
      of many developmental processes. Therefore, identification and characterization
      of binding sites of transcription factors are important for uncovering the
      mechanisms of a particular developmental process. Here, we describe detailed
      procedures for genome-wide analysis of binding sites of a transcription factor
      involved in the fiber-type differentiation of skeletal muscle. By conducting ChIP
      seq followed by a series of downstream analyses, in-depth information on binding
      sites of transcription factors can be obtained in a genome-wide manner.

PMID- 23975786
TI  - Analysis of allele-specific gene expression using a target-oriented tiling
      microarray assay.
AB  - Advances in molecular and computational biology in recent years have led to the
      development or the improvement of methods for analyzing global gene expression.
      In most of these efforts, it is assumed that alleles of different origins
      contribute equally to the transcript pool. However, accumulating evidence
      suggests that many genes are not equally expressed from the paternal and maternal
      chromosomes. In addition to imprinting, the phenomenon of imbalanced allelic
      expression is widespread in heterozygous individuals. To distinguish transcript
      pools derived from different alleles present in the same organism, a number of
      methods have been developed. Here, we describe an oligonucleotide tiling
      microarray-based assay for analyzing allele-specific gene expression.
      Specifically targeting single-nucleotide polymorphisms, this two-step assay
      offers a high-throughput and multiplex method for detecting and quantifying
      unequal allelic expression that is readily applicable to many experimental
      systems. 

PMID- 23975787
TI  - Detection of epigenetic alterations using tiling arrays.
AB  - The epigenetic status of cancer cells is a consequence of the neoplastic
      transformation of their normal counterpart. Epigenetic changes directly influence
      gene expression and chromatin organization, which consequently leads to escape
      from the tumor-suppression mechanisms. Global mapping for specific epigenetic
      modifications (e.g., DNA methylation) of the entire genome is required to reveal
      epigenetic hotspots associated with a cancer type/stage. DNA tiling arrays may be
      applied for genome-wide analysis of different epigenetic marks. Tiling arrays are
      high-density DNA microarrays that can be custom-made to survey regions of
      interest (e.g., gene promoters) or permit whole-genome analysis. To identify the
      genomic alterations associated with testicular cancers we used tiling arrays to
      profile their methylome. We successfully identified numerous epigenetically
      modified loci that arose as a consequence of tumor progression.

PMID- 23975788
TI  - Investigating gene promoter methylation in a mouse model of status epilepticus.
AB  - Epigenetic modification of DNA by methylation of the cytosine present in CG
      dinucleotides constitutes a key regulatory mechanism in the control of gene
      expression in neurological diseases. In this chapter, we describe an in-depth
      methodology of methylated DNA immunoprecipitation used in combination with tiling
      microarrays (MeDIP-chip) in order to analyze genome-wide gene promoter
      methylation in the hippocampus of mice following status epilepticus (prolonged
      seizure). While a specific mouse model and array format are described, the method
      can be applied to DNA from many tissues to analyze the methylation status of
      promoter regions across whole genomes, using a wide range of available array
      formats (both custom designed and commercially catalogued). We conclude the
      chapter with the description of bisulfite sequencing validation of MeDIP-chip
      results.

PMID- 23975789
TI  - Integrative analysis of ChIP-chip and ChIP-seq dataset.
AB  - Epigenetic regulation and interactions between transcription factors and
      regulatory genomic regions play crucial roles in controlling transcriptional
      regulatory networks that drive development, environmental responses, and disease.
      Chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP
      seq) and ChIP followed by genomic tiling microarray hybridization (ChIP-chip) are
      the two of the most widely used technologies for genome-wide identification of
      DNA protein interactions and histone modification in vivo. Many algorithms and
      tools have been developed and evaluated that allow identification of
      transcription factor binding sites from ChIP-seq or ChIP-chip datasets. However,
      binding site identification is only the first step; the ultimate goal is to
      discover the regulatory network of the transcription factor (TF). Here, we
      present a common workflow for downstream analysis of ChIP-chip and ChIP-seq with
      an emphasis on annotating binding sites and integration with gene expression data
      to identify direct and indirect targets of the TF. These tools will help with the
      overall goal of unraveling transcriptional regulatory networks using datasets
      publicly available in GEO.

PMID- 23975790
TI  - HAT: a novel statistical approach to discover functional regions in the genome.
AB  - Tiling arrays are useful for exploring local functions of regions of the genome
      in an unbiased fashion. The exact determination of those genomic regions based on
      tiling-array data, e.g., generated by means of hybridization with
      immunopreciptated DNA-fragments to the arrays is a challenge. Many different
      statistical methodologies have been developed to find biological relevant regions
      of-interest (ROI) by using the quantitative signal intensity of each probe. We
      previously developed a method called Hypergeometric Analysis of Tiling arrays
      (HAT) for the analysis of tiling-array data, but it is developed such that it can
      also be used to study data derived by genome-wide deep sequencing approaches.
      Here we applied HAT to analyze two publicly available tiling-array data sets.
      After the detection of statistically significant ROI, these are often used in
      additional analysis for hypothesis testing. We therefore discuss, by using the
      results of the tiling-array experiment, pathway and motif analyses. 

PMID- 23975791
TI  - Inference of alternative splicing from tiling array data.
AB  - Alternative splicing (AS) is an important mechanism implicated in eukaryotic gene
      expression, whereby exon segments of precursor-mRNA transcripts are joined
      together in different arrangements corresponding to diverse isoforms of mature
      mRNA. Accumulating evidence suggests that in many instances this process is
      specifically regulated and contributes to the structural and functional
      diversification of tissues and cell types. Furthermore, several studies support
      the view that environmental stresses dramatically impact on AS and reported the
      presence of novel transcript isoforms in response to biotic or abiotic stresses.
      Since specific regulation of AS in plants is a largely unexplored field of
      research, large-scale approaches aimed at monitoring AS on a genome-wide level
      are of increasing importance to gain insights into tissue-specific splicing
      regulation and to study the effects of changed environmental conditions on pre
      mRNA splicing.Here, we describe the concepts of a traditional statistical
      approach, and a more recently developed machine learning-based method for AS
      detection from tiling arrays. The here presented approaches were employed for the
      detection and profiling of AS events in the model plant A. thaliana, and applied
      to a large dataset comprising transcriptomic expression data from 11 tissues and
      13 stress conditions. 

PMID- 23975792
TI  - Analysis of in vivo occupancy of Aebp1, a transcription factor, using high
      resolution tiling array.
AB  - Aebp1 is a transcription factor that negatively regulates adipogenesis and also
      is upregulated in primary GBM as against secondary GBM. Here we describe a
      systematic approach to map the in vivo occupancy sites of Aebp1 by using a
      combination of chromatin immune-precipitation technique and hybridization to
      Agilent high resolution human promoter tiling array (2*224) containing 474393
      probes. We also describe the use of various bioinformatics tools for analysis of
      the hybridization data and identification of Aebp1 occupancy sites in U87MG
      glioma cell line.

PMID- 23975793
TI  - Application of the simple and efficient Mpeak modeling in binding peak
      identification in ChIP-chip studies.
AB  - Chromatin immunoprecipitation and hybridization of high-density promoter
      microarray (ChIP-chip) is a powerful strategy to identify target genes for
      specific transcription factors and other DNA-binding nuclear proteins in a genome
      wide manner. Services of core facilities have greatly enhanced the accessibility
      of these technologies to new investigators to the field. The Mpeak modeling is a
      simple and efficient computer program, capable of identifying chromatin-binding
      peaks in ChIP-chip datasets. It utilizes advanced statistical computation, but
      yet offers a simple procedure with user inputs on parameters in its operation.
      The Mpeak-fitted signals are tabulation in convenient formats and can be
      visualized in various genome-display graphic programs, including SignalMap and
      Genome Browser, and analyzed together with other datasets, such as microarray
      expression patterns. Several research groups have used the Mpeak program in their
      respective ChIP-chip studies. The various features of Mpeak will be illustrated
      with ChIP-chip datasets from a study designed to identify the target genes for
      the sex-determining factor, SRY, in mouse embryonic gonads at the time of sex
      determination.

PMID- 23975794
TI  - Evaluation of MeDIP-chip in the context of whole-genome bisulfite sequencing
      (WGBS-seq) in Arabidopsis.
AB  - Studies of DNA methylation in Arabidopsis have rapidly advanced from the analysis
      of a single reference accession to investigations of large populations. The goal
      of emerging population studies is to detect differentially methylated regions
      (DMRs) at the genome-wide scale, and to relate this variation to gene expression
      and phenotypic diversity.Whole-genome bisulfite sequencing (WGBS-seq) has
      established itself as a gold standard in DNA methylation analysis due to its high
      accuracy and single cytosine measurement resolution. However, scaling up the use
      of this technology for large population studies is currently not only cost
      prohibitive but also poses nontrivial bioinformatic challenges. If the end-point
      of the study is to detect DMRs at the level of several hundred base pairs rather
      than at the level of single cytosines, low-resolution array-based methods, such
      as MeDIP-chip, may be entirely sufficient. However, the trade-off between
      measurement accuracy and experimental/analytical practicality needs to be
      weighted carefully. To help make such experimental choices, we conducted a side
      by-side comparison between the popular dual-channel MeDIP-chip Nimblegen
      technology and Illumina WGBS-seq in two independent Arabidopsis lines.Our
      analysis shows that MeDIP-chip performs reasonably well in detecting DNA
      methylation at probe-level resolution, yielding a genome-wide combined false
      positive and false-negative rate of about 0.21. However, detection can be
      susceptible to strong signal distortions resulting from a combination of dye bias
      and the CG content of effectively unmethylated genomic regions. We show that
      these issues can be easily bypassed by taking appropriate data preparation steps
      and applying suitable analysis tools.We conclude that MeDIP-chip is a reasonable
      alternative to WGBS-seq in emerging Arabidopsis population epigenetic studies.

PMID- 23975795
TI  - Mapping genomic features of tiling microarray data by TileMapper.
AB  - The recent revolution of genomics techniques has allowed the detection of various
      sequence features and biological variations on whole-genome scale. However, these
      high-resolution data present significant challenges for experimental biologists
      to understand and analyze. The conventional way is to use genome browsers to
      locate and visualize regions of interest. But it lacks user-friendly data mining
      functionality. Here we present a protocol that allows rapid annotation of genomic
      coordinate data by using TileMapper. Interesting biological annotations from
      large-scale genomic data, such as transcriptome analysis, chromatin
      immunoprecipitation on chip, or methyl-DNA immunoprecipitation (MeDIP) studies
      generated from the tiling microarrays and other platforms, could be analyzed
      without requiring computational skills. The outputs are saved in tabulated
      format, which permit flexible and simple processing in spreadsheet software, or
      to be exported to other pipelines for subsequent analysis. 

PMID- 23975796
TI  - Gated communities: apoplastic and symplastic signals converge at plasmodesmata to
      control cell fates.
AB  - Due to their rigid cell walls, plant cells can only communicate with each other
      either by symplastic transport of diverse non-cell autonomous signalling
      molecules via plasmodesmata (PDs) or by endo- and exocytosis of signalling
      molecules via the extracellular apoplastic space. PDs are plasma membrane-lined
      channels spanning the cell wall between neighbouring cells, allowing the exchange
      of molecules by symplastic movement through them. This review focuses on
      developmental decisions that are coordinated by short- and long-distance
      communication of cells via PDs. We propose a model combining both apoplastic and
      symplastic signalling events via secreted ligands and their PD-localized receptor
      kinases which gate the symplastic transport of information molecules through PDs.
      Cell communities can thus coordinate cell-fate decisions non-cell autonomously by
      connecting or disconnecting symplastic subdomains. Here we concentrate on the
      establishment of such subdomains in the plant's primary meristems that serve to
      maintain long-lasting stem cell populations in the shoot and root apical
      meristems, and discuss how apoplastic signalling via transport of information
      molecules through PDs is integrated with symplastic feedback signalling events. 

PMID- 23975797
TI  - Expanding the concept of significant choice through consideration of health
      literacy during crises.
AB  - Nilsen defined the concept of the ethic of significant as "choice making that is
      voluntary, free from physical or mental coercion . . . based on all the
      information available when the decision must be made." This study highlights the
      importance of speakers in crisis situations not only meeting the ethical
      stipulations of significant choice but also taking into consideration the health
      literacy of their audience. Health literacy is defined as the ability of
      individuals to gather, interpret, and understand information regarding health
      matters. To advance this claim, a case study involving a food recall is examined.
      Television news coverage was analyzed to observe the importance of both
      significant choice and health literacy in such public communication. The
      findings, from the standpoint of significant choice and health literacy, indicate
      that the messages disseminated during this crisis failed to account for a notable
      portion of the audience. From a practical standpoint this study asserts that
      clear and open communication cannot be considered only from the perspective of
      the party sending the message. Rather, careful consideration of the audience's
      ability to comprehend and act on the information is equally important. 

PMID- 23975798
TI  - Engaging students in community health: a public health advocacy curriculum.
AB  - Individual risk assessment and behavior change dominate the content of high
      school health education instruction whereas broader social, political, and
      economic factors that influence health-known as upstream causes-are less commonly
      considered. With input from instructors and students, we developed a 10-lesson
      experiential Public Health Advocacy Curriculum that uses classroom-based
      activities to teach high school students about the upstream causes of health and
      engages them in community-based health advocacy. The Curriculum, most suitable
      for health- or advocacy-related elective classes or after-school programs, may be
      taught in its entirety or as single lessons integrated into existing coursework.
      Although students at many schools are using the Curriculum, it has been formally
      evaluated with 110 predominantly Latino students at one urban and one semirural
      public high school in Northern California (six classes). In pre-post surveys,
      students showed highly significant and positive changes in the nine questions
      that covered the three main Curriculum domains (Upstream Causes, Community
      Exploration, and Public Health Advocacy), p values .02 to <.001. The Curriculum
      is being widely disseminated without charge to local, national, and international
      audiences, with the objective of grooming a generation of youth who are committed
      to the public health perspective to health. 

PMID- 23975799
TI  - Testing Hardy-Weinberg equilibrium with a simple root-mean-square statistic.
AB  - We provide evidence that, in certain circumstances, a root-mean-square test of
      goodness of fit can be significantly more powerful than state-of-the-art tests in
      detecting deviations from Hardy-Weinberg equilibrium. Unlike Pearson's $?chi ^2$
      test, the log-likelihood-ratio test, and Fisher's exact test, which are sensitive
      to relative discrepancies between genotypic frequencies, the root-mean-square
      test is sensitive to absolute discrepancies. This can increase statistical power,
      as we demonstrate using benchmark data sets and simulations, and through
      asymptotic analysis. 

PMID- 23975800
TI  - Censored quantile regression with recursive partitioning-based weights.
AB  - Censored quantile regression provides a useful alternative to the Cox
      proportional hazards model for analyzing survival data. It directly models the
      conditional quantile of the survival time and hence is easy to interpret.
      Moreover, it relaxes the proportionality constraint on the hazard function
      associated with the popular Cox model and is natural for modeling heterogeneity
      of the data. Recently, Wang and Wang (2009. Locally weighted censored quantile
      regression. Journal of the American Statistical Association 103, 1117-1128)
      proposed a locally weighted censored quantile regression approach that allows for
      covariate-dependent censoring and is less restrictive than other censored
      quantile regression methods. However, their kernel smoothing-based weighting
      scheme requires all covariates to be continuous and encounters practical
      difficulty with even a moderate number of covariates. We propose a new weighting
      approach that uses recursive partitioning, e.g. survival trees, that offers
      greater flexibility in handling covariate-dependent censoring in moderately high
      dimensions and can incorporate both continuous and discrete covariates. We prove
      that this new weighting scheme leads to consistent estimation of the quantile
      regression coefficients and demonstrate its effectiveness via Monte Carlo
      simulations. We also illustrate the new method using a widely recognized data set
      from a clinical trial on primary biliary cirrhosis. 

PMID- 23975801
TI  - Generation and characterization of epiblast stem cells from blastocyst-stage
      mouse embryos.
AB  - Mouse epiblast stem cells (EpiSCs) are pluripotent embryonic cells that can be
      used to interrogate developmental transitions that occur during gastrulation.
      EpiSCs can also be robustly differentiated into functional somatic and germ cell
      derivatives making them a useful tool for studying development and regenerative
      medicine. Typically, mouse EpiSCs are isolated from the early postimplantation
      epiblast around 5.5 days post coitum (dpc). This chapter describes the methods
      for isolation of mouse EpiSCs from preimplantation blastocyst-stage mouse embryos
      (3.5 dpc). This technique enables the routine ability to derive EpiSC lines as it
      is much less labor intensive than isolation of EpiSCs from the postimplantation
      epiblast. We also detail relevant assays used to characterize new EpiSC lines and
      distinguish them from mouse embryonic stem cells.

PMID- 23975802
TI  - Reversion of mouse postimplantation epiblast stem cells to a naive pluripotent
      state by modulation of signalling pathways.
AB  - Mouse postimplantation epiblast cultured in activin and basic fibroblast growth
      factor gives rise to continuously growing epiblast stem cells (EpiSCs) that share
      key properties with postimplantation epiblast, such as DNA methylation and an
      inactive X-chromosome. EpiSCs also show a distinct gene expression profile
      compared to embryonic stem cells (ESCs) derived from preimplantation blastocysts,
      and do not contribute efficiently to chimeras. EpiSCs can, however, revert to
      pluripotent ESC-like cells upon exposure to leukemia inhibitory factor-Stat3
      signalling on feeder cells. Here we describe a protocol for the establishment of
      EpiSCs and their reversion to ESCs.

PMID- 23975803
TI  - Converting mouse epiblast stem cells into mouse embryonic stem cells by using
      small molecules.
AB  - The derivation of mouse embryonic stem cells (mESCs) from the inner cell mass
      (ICM) of mouse preimplantation blastocysts has provided tremendous opportunities
      in exploring mammalian development and pluripotent stem cell biology (Martin,
      Proc Natl Acad Sci U S A 78(12):7634-7638, 1981; Evans and Kaufman, Nature
      292(5819):154-156, 1981). The progresses of mESC studies also enabled the
      subsequent establishment of human ESCs (hESCs) from human embryos (Thomson et
      al., Science 282(5391):1145-1147, 1998). However, it had been a long-standing
      mystery why mESCs and hESCs exhibit distinct differences in terms of self-renewal
      signaling dependence and cell culture behaviors, such as colony morphology and
      response to single-cell dissociation, although both of them are pluripotent.
      Recently, a novel type of pluripotent stem cells were isolated from the
      postimplantation egg cylinder-stage epiblasts of mouse and rat (Tesar et al.,
      Nature 448(7150):196-199, 2007; Brons et al., Nature 448(7150):191-195, 2007),
      and were named epiblast stem cells (EpiSCs). Interestingly, mouse EpiSCs
      (mEpiSCs) closely resemble hESCs in respect of the colony morphology and self
      renewal dependence. These results suggest that different pluripotent states exist
      during mammalian development: the mESC-like state representing the
      preimplantation ICM and hESC/mEpiSC-like state representing later epiblast cells.
      This chapter introduces methods of converting mEpiSCs back to mESCs through
      chemical approaches.

PMID- 23975804
TI  - Isolation and culture of rabbit embryonic stem cells.
AB  - Mammalian stem cells are invaluable research resources for the study of cell and
      embryonic development as well as practical tools for use in the production of
      genetically engineered animals and further therapeutics. It is important that we
      further our knowledge and understanding of a variety of stem cells from several
      different animal species before trials in humans commence. Here we describe
      methods for establishing rabbit embryonic stem (rES) cell lines with indefinite
      proliferation potential. rES cells attain maximum proliferation potential when
      cultured at a feeder cell density of one-sixth of that of full confluency. Higher
      and lower densities of feeder cells induced ES cell differentiation or division
      arrest. Fibroblast growth factor (FGF)2 can maintain the undifferentiated status
      of rES cells; however leukemia inhibitory factor (LIF) is dispensable. Under
      optimized conditions, rES cells could be passaged by trypsinization 50 times.
      This culture system enabled efficient gene transduction and clonal expansion from
      single cells. rES cells grew as flat monolayer cell colonies, as reported for
      monkey and human ES cells, and expressed pluripotency markers. Embryoid bodies
      and teratomas formed readily in vitro and in vivo, respectively. Characterization
      of ES cells from different species is important for establishing common features
      of pluripotency. We have demonstrated the similarity of ES cells between rabbit
      and humans. These cell lines could be applied directly using gene-targeting
      techniques, or in combination with induced pluripotent stem cells. Thus, rES
      cells are a suitable model for studying human transplantation therapy and disease
      treatments. 

PMID- 23975805
TI  - Goat embryonic stem-like cell derivation and characterization.
AB  - Embryonic stem (ES) cells are derived from the inner cell masses of
      preimplantation embryos. ES cells are pluripotent cells with the capacity for
      long-term propagation and broad differentiation plasticity. These cells have an
      exceptional functional feature in that they can differentiate into all tissues
      and organs, including germ cells. Established ES cell lines have been generated
      in mouse, human, and nonhuman primate but derivation of ES cells in farm animals
      has been problematic. Several ES-like cell lines from farm animals have been
      reported to exhibit properties of pluripotency in vitro. However, only a few of
      them morphologically resemble ES cells, or express markers that are associated
      with established ES cell lines from mouse and humans. Methods for derivation,
      propagation, and differentiation of ES cells from domestic animals have not been
      fully established. In this chapter, we describe methods for isolation of goat ES
      (gES) cell lines from in vivo-derived blastocysts and characterization of markers
      indicative of pluripotency. In addition, we outline differentiation of gES cells
      into all three germ layers in vivo by forming teratomas as a hallmark of
      pluripotency. 

PMID- 23975806
TI  - Derivation and culture of canine embryonic stem cells.
AB  - The derivation of canine embryonic stem cells (cESCs) represents a significant
      achievement and opens the door to further stem cell research and therapies in the
      dog. Canines share a common environment with humans and exhibit a host of genetic
      diseases, many of which have human parallels. Thus, the canine model presents
      unique advantages over other currently used organisms to help develop stem cell
      therapies in humans. To reveal the therapeutic potential of cESCs further basic
      research on the molecular mechanisms controlling their pluripotency and self
      renewal characteristics is needed. Herein, we present the methods for derivation
      and culture of cESCs. Following collection of the canine blastocyst, two
      derivation methods are presented; immunodissection and whole blastocyst explant.
      These two methods lead to cESCs differing in morphology and subculture
      techniques. Additional protocols for subculture of established lines, feeder-free
      culture, and cryopreservation protocols are also described.

PMID- 23975807
TI  - Isolation and culture of porcine embryonic stem cells.
AB  - Despite their agricultural and biomedical importance, embryonic stem cells (ESCs)
      are yet to be isolated for the pig or the domestic ungulates in general. This
      suggests that methods which have been used successfully in mice may not be
      applicable to these. In this chapter we describe a new method for the isolation
      of porcine ESCs. This method differs from those described previously in that it
      produces homogeneous outgrowths from undifferentiated inner cell mass cells when
      embryos are plated onto inactivated mouse embryonic feeder layers.

PMID- 23975808
TI  - Isolation and culture of pig epiblast stem cells.
AB  - Regulation of early development can be directly interrogated in the embryo or can
      be studied in cultured cells isolated in the laboratory. New understanding of the
      developmental stages and the signalling requirements of the pig embryo have
      enabled the development of improved protocols for the derivation of pluripotent
      cells from early epiblasts. Here, we provide a detailed step-by-step description
      of the critical parameters required for isolation and establishment of these
      cells and how they can be used to study their developmental properties.

PMID- 23975809
TI  - Isolation and culture of bovine embryonic stem cells.
AB  - Isolation and culture of primary embryonic stem (ES) cell colonies are the first
      critical step towards establishment of stable ES cell lines. Here we introduce a
      novel method designated as "Separate and Seed" that contributes remarkably to
      efficient derivation of bovine primary ES cell colonies from blastocysts. The
      bovine ES cell colonies can self-renew to passage 10 with the growth factors bFGF
      and BIO. The bovine ES cells exhibit morphology typical of ES cells and express
      pluripotent molecular markers including Oct4, Nanog, SSEA1, SSEA4, and alkaline
      phosphatase (AP). These pluripotent markers may be used for the characterization
      of authentic bovine ES cell lines. Although continued efforts are required for
      improving long-term culture of bovine ES cells, this novel "Separate and Seed"
      method plus the growth factors bFGF and BIO provides an initial effective step
      that may eventually lead to the derivation of authentic bovine ES cells.

PMID- 23975810
TI  - Analysis of molecular markers for staging peri-gastrulating bovine embryos.
AB  - Whole-mount in situ hybridization (WISH) is a method to visualize gene expression
      through hybridization of in vitro synthesized riboprobes to cellular mRNAs. WISH
      has been used in developmental biology for decades and was adapted to many
      species, especially for model organisms of developmental biology. The method has
      evolved, from analyzing small embryo batches to large-scale gene expression
      screenings, using: (1) manual or automated protocols, (2) colorimetric or
      fluorescent detection of the hybridized riboprobes, and (3) individual or
      systemic image acquisition and storage. As for bovine embryo staging, the in situ
      hybridization of whole embryonic discs has both proved useful and efficient,
      provided that a few improvements were brought to the in vitro riboprobe
      synthesis.

PMID- 23975811
TI  - Chicken embryonic stem cells: establishment and characterization.
AB  - Embryonic stem (ES) cells are unique models for investigating early development
      and cell differentiation. First identified in mouse and later in other mammals,
      these cells have also been isolated in avian species. Here, using chicken as a
      model, we describe a set of protocols allowing the isolation, maintenance,
      genetic modification, differentiation, and injection of the chicken embryonic
      stem (cES) cells into embryos for obtaining chimeric animals. 

PMID- 23975812
TI  - Manipulating the avian epiblast and epiblast-derived stem cells.
AB  - Compared to eutherian mammals, birds retain a primitive form of epiblast
      development. Molecular studies of the avian epiblast can provide valuable insight
      for mammalian epiblast research. Here, we introduce several basic techniques in
      handling epiblast-stage embryos of the chick, the major model organism for avian
      developmental biology studies. We describe how to collect embryos for RNA
      extraction and gene expression analysis, to set up ex ovo New culture for
      overexpression, bead graft and small molecule-based inhibitor studies, and to
      carry out whole-mount RNA in situ hybridization analysis. We introduce a novel
      and simple method for molecular perturbation of the epiblast differentiation in
      ovo. We also describe how to perform primary chicken epiblast cell culture, to
      establish stable epiblast stem cell (Epi-SC) lines, and to assay for pluripotency
      in primary epiblast cells and Epi-SCs. 

PMID- 23975813
TI  - Stepwise differentiation from naive state pluripotent stem cells to functional
      primordial germ cells through an epiblast-like state.
AB  - A group of pluripotent cells appearing during mammalian embryogenesis is the
      source for all the cell lineages that compose the embryo proper. In mice,
      pluripotent cells are first established in the inner cell mass (ICM) of the
      preimplantation blastocyst. After implantation, the ICM soon transforms into a
      cup-shaped epithelium, called the postimplantation epiblast. The two types of
      pluripotent cells, the ICM and postimplantation epiblast cells, are distinct,
      based on the differences in their gene expression profiles, epigenetic status,
      and differentiation capacity. During gastrulation, some of the postimplantation
      epiblast cells adjacent to the extraembryonic ectoderm are specified as
      primordial germ cells (PGCs), precursors of the germ cell lineage, in response to
      bone morphogenetic protein 4 (BMP4). Recently, we succeeded in reconstituting
      epiblast differentiation and PGC specification in vitro using pluripotent stem
      cells. Here, we describe the culture method of a stepwise differentiation from
      pluripotent stem cells to functional PGCs.

PMID- 23975814
TI  - Isolation and culture of porcine neural progenitor cells from embryos and
      pluripotent stem cells.
AB  - The isolation and culture of neural progenitor cells (NPCs) from pluripotent stem
      cells has facilitated in vitro mechanistic studies of diseases related to the
      nervous system, as well as discovery of new medicine. In addition, NPCs are
      envisioned to play a crucial role in future cell replacement therapy. The pig has
      become recognized as an important large animal model and establishment of in
      vitro-derived porcine NPCs would allow for preclinical safety testing by
      transplantation in a porcine biomedical model. In this chapter, a detailed method
      for isolation and in vitro culture of porcine NPCs from porcine embryos or
      induced pluripotent stem cells is presented. The neural induction is performed in
      coculture and the isolation of rosette structures is carried out manually to
      ensure a homogenous population of NPCs. Using this method, multipotent NPCs can
      be obtained in approximately 1 month. The cells have the potential of long-term
      culture and the ability to differentiate into neural and glial cells.

PMID- 23975815
TI  - Derivation of neural precursors from bovine preimplantation embryos.
AB  - Induction of neural differentiation from embryonic pluripotent stem cells
      (ES/EpiSc), both of mouse and primates, has been extensively published by several
      research teams. However, direct derivation of organized neuroectoderm in vitro
      from blastocyst stage embryos of rodents or primates has not been reported so
      far. Here we describe a method of direct neural differentiation from the inner
      cell mass cells of preimplantation bovine embryos, without the intermediate step
      of ES/EpiSc cells derivation (Lazzari et al., Stem cells 24:2514-2521, 2006).
      Proliferating neural precursors cells lines, and both central and peripheral
      nervous system derivatives, can be obtained providing a unique in vitro model of
      early neurulation events in mammals.

PMID- 23975816
TI  - General overview of neuronal cell culture.
AB  - In this introductory chapter, we provide a general overview of neuronal cell
      culture. This is a rapidly evolving area of research and we provide an outline
      and contextual framework for the different chapters of this book. These chapters
      were all contributed by scientists actively working in the field who are
      currently using state-of-the-art techniques to advance our understanding of the
      molecular and cellular biology of the central nervous system. Each chapter
      provides detailed descriptions and experimental protocols for a variety of
      techniques ranging in scope from basic neuronal cell line culturing to advanced
      and specialized methods. 

PMID- 23975817
TI  - Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology.
AB  - The use of primary mammalian neurons derived from embryonic central nervous
      system tissue is limited by the fact that once terminally differentiated into
      mature neurons, the cells can no longer be propagated. Transformed neuronal-like
      cell lines can be used in vitro to overcome this limitation. However, several
      caveats exist when utilizing cells derived from malignant tumors. In this
      context, the popular SH-SY5Y neuroblastoma cell line and its use in in vitro
      systems is described. Originally derived from a metastatic bone tumor biopsy, SH
      SY5Y (ATCC((r)) CRL-2266TM) cells are a subline of the parental line SK-N-SH
      (ATCC((r)) HTB-11TM). SK-N-SH were subcloned three times; first to SH-SY, then to
      SH-SY5, and finally to SH-SY5Y. SH-SY5Y were deposited to the ATCC((r)) in 1970
      by June L. Biedler.Three important characteristics of SH-SY5Y cells should be
      considered when using these cells in in vitro studies. First, cultures include
      both adherent and floating cells, both types of which are viable. Few studies
      address the biological significance of the adherent versus floating phenotypes,
      but most reported studies utilize adherent populations and discard the floating
      cells during media changes. Second, early studies by Biedler's group indicated
      that the parental differentiated SK-N-SH cells contained two morphologically
      distinct phenotypes: neuroblast-like cells and epithelial-like cells (Ross et
      al., J Nat Cancer Inst 71:741-747, 1983). These two phenotypes may correspond to
      the "N" and "S" types described in later studies in SH-SY5Y by Encinas et al. (J
      Neurochem 75:991-1003, 2000). Cells with neuroblast-like morphology are positive
      for tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase characteristic of
      catecholaminergic neurons, whereas the epithelial-like counterpart cells lacked
      these enzymatic activities (Ross et al., J Nat Cancer Inst 71:741-747, 1983).
      Third, SH-SY5Y cells can be differentiated to a more mature neuron-like phenotype
      that is characterized by neuronal markers. There are several methods to
      differentiate SH-SY5Y cells and are mentioned below. Retinoic acid is the most
      commonly used means for differentiation and will be addressed in detail. 

PMID- 23975818
TI  - Cultured cell line models of neuronal differentiation: NT2, PC12.
AB  - The lack of a convenient, easily maintained and inexpensive in vitro human
      neuronal model to study neurodegenerative diseases, prompted us to develop a
      rapid, 1-h differentiated neuronal cell model based on human NT2 cells and C3
      transferase. Here, we describe the rapid differentiation of human neuronal NT2
      cells, and the differentiation, transduction and transfection of rat PC12 cells
      to obtain cells with the morphology of differentiated neurons that can express
      exogenous genes of interest at high level. 

PMID- 23975819
TI  - Murine teratocarcinoma-derived neuronal cultures.
AB  - This chapter describes the culture and propagation of murine embryonic stem
      cells, F9 and P19 and strategies for differentiation of these stem cells into
      neurons. Protocols focus on maintenance and propagation of these cells and
      routine procedures employed for differentiation into neuronal cells. Additional
      protocols are also described for obtaining enriched populations of mature neurons
      from P19 cells and differentiation of F9 cells into serotonergic or
      catecholaminergic neurons.The protocols described herein can be employed for
      dissection of the pathways such as gliogenesis and neurogenesis that are involved
      in differentiation of pluripotent stem cells such as F9 and P19 into glial cells
      or terminally differentiated neurons. 

PMID- 23975820
TI  - Isolation and propagation of primary human and rodent embryonic neural progenitor
      cells and cortical neurons.
AB  - The research on human neural progenitor cells holds great potential for the
      understanding the molecular programs that control differentiation of cells of
      glial and neuronal lineages and pathogenetic mechanisms of neurological diseases.
      Stem cell technologies provide also opportunities for pharmaceutical industry to
      develop new approaches for regenerative medicine. Here we describe the protocol
      for isolation and maintenance of neural progenitor cells and cortical neurons
      using human fetal brain tissue. This protocol can be successfully adapted for
      preparation of rodent neural and oligodendrocyte progenitor cells. While several
      methods for isolation of neural and oligodendrocyte progenitors from rodent brain
      tissue have been described, including techniques which use gene transfer and
      magnetic resonance beads, few methods are focused on derivation of human
      oligodendrocyte progenitor cells. Development of human culture provides the most
      physiologically relevant system for investigation of mechanisms which regulate
      function of oligodendrocyte, specifically of human origin. 

PMID- 23975821
TI  - Mouse enteric neuronal cell culture.
AB  - In the enteric nervous system, there exist a lot of local intrinsic neurons which
      control the gastrointestinal functions. Culture of enteric neurons provides a
      good model system for physiological, electrophysiological, and pharmacological
      studies. Here, we describe two methods to obtain sufficient enteric neurons from
      mouse myenteric plexuses by directly culturing primary neurons or inducing
      neuronal differentiation of enteric neural stem/progenitor cells. 

PMID- 23975822
TI  - Preparation of neural stem cells and progenitors: neuronal production and
      grafting applications.
AB  - Neural stem cells (NSC) are not only a valuable tool for the study of neural
      development and function, but an integral component in the development of
      transplantation strategies for neural disease. NSC can be used to study how
      neurons acquire distinct phenotypes and how the reciprocal interactions between
      neurons and glia in the developing nervous system shape the structure and
      function of the central nervous system (CNS). In addition, neurons prepared from
      NSC can be used to elucidate the molecular basis of neurological disorders as
      well as potential treatments. Although NSC can be derived from different species
      and many sources, including embryonic stem cells, induced pluripotent stem cells,
      adult CNS, and direct reprogramming of non-neural cells, isolating primary NSC
      directly from rat fetal tissue is the most common technique for preparation and
      study of neurons with a wealth of data available for comparison. Regardless of
      the source material, similar techniques are used to maintain NSC in culture and
      to differentiate NSC toward mature neural lineages. This chapter will describe
      specific methods for isolating multipotent NSC and neural precursor cells (NPC)
      from embryonic rat CNS tissue (mostly spinal cord). In particular, NPC can be
      separated into neuronal and glial restricted precursors (NRP and GRP,
      respectively) and used to reliably produce neurons or glial cells both in vitro
      and following transplantation into the adult CNS. This chapter will describe in
      detail the methods required for the isolation, propagation, storage, and
      differentiation of NSC and NPC isolated from rat spinal cords for subsequent in
      vitro or in vivo studies. 

PMID- 23975823
TI  - Derivation of neuronal cells from fetal normal human astrocytes (NHA).
AB  - Pathological changes in most neurological diseases are marked by cell loss. To
      understand the mechanisms of neurogenesis and brain repair at a cellular level,
      observation on less complex systems provide valuable knowledge which offer the
      basis for therapeutic interventions. This has been the impetus for neural cell
      culture studies and the development of in vitro models. Here, we provide
      protocols for differentiation into neuronal lineage of commercially available
      normal human astrocytes (NHA) that are isolated from normal fetal human brain
      (Lonza, Inc.). It is known that some of GFAP positive astrocytic cells have
      stem/progenitor cell characteristics; however, understanding of the human GFAP
      positive cells with these characteristics remains limited. The genesis of
      neuronal lineage cells from the NHA occurs in adherent culture conditions by
      removal of serum and exposure to bFGF. When transferred to serum-free medium
      supplemented with bFGF, NHA cells generate neuronal precursors that express
      doublecortin, nestin and are negative for GFAP. After withdrawal of bFGF they
      mature into neurons. The average time required for generation of neuronal cells
      using this protocol is about 3 weeks. Our model of neurogenesis captures a
      contained in vitro system consisting of both neurons and glia. This "human brain
      in a dish" model can be used to assay the effects of interventions on developing
      human neurons at a cellular and molecular level and is also suitable for modeling
      of various aspects of human diseases and testing of novel therapeutic strategies.

PMID- 23975824
TI  - Slice culture modeling of central nervous system (CNS) viral infection.
AB  - The complexity of the central nervous system (CNS) is not recapitulated in cell
      culture models. Thin slicing and subsequent culture of CNS tissue has become a
      valued means to study neuronal and glial biology within the context of the
      physiologically relevant tissue milieu. Modern membrane-interface slice culturing
      methodology allows straightforward access to both CNS tissue and feeding medium,
      enabling experimental manipulations and analyses that would otherwise be
      impossible in vivo. CNS slices can be successfully maintained in culture for up
      to several weeks for investigation of evolving pathology and long-term
      intervention in models of chronic neurologic disease.Herein, membrane-interface
      slice culture models for studying viral encephalitis and myelitis are detailed,
      with emphasis on the use of these models for investigation of pathogenesis and
      evaluation of novel treatment strategies. We describe techniques to (1) generate
      brain and spinal cord slices from rodent donors, (2) virally infect slices, (3)
      assess virally induced injury/apoptosis, (4) characterize "CNS-specific" cytokine
      production, and (5) treat slices with cytokines/pharmaceuticals. Although our
      focus is on CNS viral infection, we anticipate that the described methods can be
      adapted to address a wide range of investigations within the fields of
      neuropathology, neuroimmunology, and neuropharmacology. 

PMID- 23975825
TI  - Neurospheres and glial cell cultures: immunocytochemistry for cell phenotyping.
AB  - Cell cultures constitute an important tool for research as a way to reproduce
      pathological processes in a controlled system. However, the culture of brain
      derived cells in monolayer presents significant challenges that obscure the
      fidelity of in vitro results. After a few number of passages, glial and neuronal
      cells begin to lose their morphological characteristics, and most importantly,
      their specific cellular markers and phenotype. In recent years, the discovery of
      Neural Progenitor Cells and the methodology to culture them in suspension
      maintaining their potentiality while still retaining the ability to differentiate
      into astrocytes, oligodendrocytes, and neurons have made significant
      contributions to the fields of neuroscience and neuropathology.In the brain,
      progenitor cells are located in the Germinal Matrix, in the subventricular zone
      and play an essential role in the homeostasis of the brain by providing the
      source to replace differentiated cells that have been lost or damaged by
      different pathological processes, such as injury, genetic conditions or disease.
      The discovery of these Neural Stem Cells in an organ traditionally thought to
      have limited or no regenerative capacity has open the door to the development of
      novel treatments, which include cell replacement therapy. Here we describe the
      culture and differentiation of neural progenitor cells from Neurospheres, and the
      phenotyping of the resulting cells using immunocytochemistry. The
      immunocytological methods outlined are not restricted to the analysis of
      Neurosphere-derived cultures but are also applicable for cell typing of primary
      glial or cell line-derived samples. 

PMID- 23975826
TI  - Transfection of neuronal cultures.
AB  - Efficient transfection of genes into neurons is a crucial step for the study of
      neuronal cell biology and functions. These include but are not limited to
      investigating gene function by overexpression of target proteins via expression
      plasmids and knocking down the expression levels of neuronal genes by RNA
      interference (RNAi). In addition, reporter gene constructs are widely used to
      investigate the promoter activities of neuronal genes. Numerous transfection
      techniques have been established to deliver genes into the cells. However,
      efficient transfection of post-mitotic cells, including neurons, still remains a
      challenging task. Here, we overview the advantages and disadvantages of various
      techniques for the transfection of primary neurons, and provide an optimized
      protocol for FuGENE-6 (Promega) which allows a suitable transfection efficiency
      of primary neuronal cultures. 

PMID- 23975827
TI  - Lentiviral transduction of neuronal cells.
AB  - Here we describe a general method for the construction of a lentivirus vector
      using a specific example of the construction of a lentivirus containing the
      luciferase reporter gene under the control of two hypothetical promoters and
      derived HIV-1 based lentivirus expression vector pLVX-Puro. This method can be
      used to compare the strength and regulation of different promoters. In this
      example, the target cells for transduction are human primary fetal astrocytes but
      the method is applicable to any primary cell culture from the CNS or other tissue
      and can be used to examine the strength of a particular promoter in different
      cell types. HIV based lentivirus particles are prepared by transfection of 4
      plasmids into 293T cells using the Fugene 6 transfection reagent.

PMID- 23975828
TI  - Compartmentalized neuronal cultures.
AB  - The culturing of neurons results in formation of the layer of neurons with random
      extensive overlapping outgrowth. To understand specific roles of somas, axons,
      and dendrites in complex function of neurons and to identify molecular mechanisms
      of biological processes in these cellular compartments various methods were
      developed. We utilized AXon Investigation System (AXISTM) manufactured by
      Millipore. This device provides an opportunity to orient neuronal outgrowth and
      spatially isolate neuronal processes from neuronal bodies. AXIS device is a slide
      mounted microfluidic system, which consists of four wells. Two of the wells are
      connected by a channel on each side of the device. Channels are connected by
      microgrooves (approximately 120). The size of microgrooves (10 MUm in width and 5
      MUm in height) do not permit passage of cell through while allowing extension of
      neurites. The microfluidic design also allows an establishment of a hydrostatic
      gradient when the volume in one chamber is greater than that in the other (Park
      et al. Nat Protocols 1: 2128-2136, 2006). This feature allows studying of the
      effect of specific compounds on selected compartments of neurons.

PMID- 23975829
TI  - Quantitative assessment of neurite outgrowth over growth promoting or inhibitory
      substrates.
AB  - The use of sensory neurons and assessment of neurite outgrowth in vitro is an
      important part of understanding neuronal development and plasticity. Cultures of
      rat dorsal root ganglion (DRG) neurons provide quantitative results very quickly
      and, when grown on growth promoting or inhibitory substrates, can be utilized to
      study axonal growth, neurotrophic dependence, structure and function of growth
      cones. Since we are interested in axon regeneration and targeting, we have sought
      to promote neurite outgrowth by refining the techniques of growing DRG neurons in
      culture. This chapter describes detailed methods for the dissection and
      purification of DRG neurons and quantitative assessment of neurite on promoting
      or inhibitory substrates. 

PMID- 23975830
TI  - A bouquet of "rosettes" in a tumor of the abdominal wall.

PMID- 23975831
TI  - Malignant renal angiomyolipoma with metastases in a child.
AB  - The biological character of epithelioid angiomyolipoma (EAML) remains
      controversial and little is known about EAML in children. We present a case of a
      7-year-old boy with abdominal distention, diagnosed as EAML. Under microscopy,
      epithelioid cells were observed, with eosinophilic or slightly eosinophilic
      cytoplasm and nuclear pleomorphism, thick-walled blood vessels, and some cells
      that were differentiated to smooth muscle cells or fat cells were easily
      observed. Immunochemical staining showed that Melan-A and HMB45 were positive.
      The tumor presented highly aggressive biobehavior. Furthermore, we reviewed and
      analyzed cases of diagnosed EAML in our hospital and those reported in the
      literature. Renal EAML (10/17) was most common, and the EAML of 3 of 17 patients
      metastasized to other organs. 

PMID- 23975832
TI  - Downregulation of tumor suppressor MBP-1 by microRNA-363 in gastric
      carcinogenesis.
AB  - Gastric carcinoma is one of the most common malignancies and the second most
      lethal cancer worldwide. The mechanisms underlying aggressiveness of gastric
      cancer still remain obscure. c-Myc promoter binding protein 1 (MBP-1) is a
      negative regulator of c-myc expression and ubiquitously expressed in normal human
      tissues. It is produced by alternative translation initiation of alpha-enolase
      gene. Both MBP-1 and alpha-enolase are involved in the control of tumorigenesis
      including gastric cancer. MicroRNAs (miRNAs) are involved in tumorigenesis and
      could have diagnostic, prognostic and therapeutic potential. In this study,
      whether miRNAs modulate tumorigenesis of gastric cancer cells through targeting
      MBP-1 was evaluated. We found that miR-363 targets 3'-untranslated region of
      human MBP-1/alpha-enolase messenger RNA. The exogenous miR-363 promotes growth,
      viability, progression, epithelial-mesenchymal transition and tumorsphere
      formation of SC-M1 gastric cancer cells through downregulation of MBP-1, whereas
      the knockdown of endogenous miR-363 suppresses tumorigenesis and progression of
      SC-M1 cells via upregulation of MBP-1. The miR-363/MBP-1 axis is also involved in
      the control of carcinogenesis in KATO III and SNU-16 gastric cancer cells.
      Furthermore, miR-363 induces the xenografted tumor growth and lung metastasis of
      SC-M1 cells through MBP-1 in vivo. Taken together, these results suggest that miR
      363 plays an important role in the increment of gastric carcinogenesis via
      targeting MBP-1. 

PMID- 23975834
TI  - Delphinidin is a novel inhibitor of lymphangiogenesis but promotes mammary tumor
      growth and metastasis formation in syngeneic experimental rats.
AB  - We have recently demonstrated that the anthocyanidin delphinidin (DEL), one of
      the most abundant dietary flavonoids, inhibits activation of ErbB and vascular
      endothelial growth factor receptor family members. These receptors play crucial
      roles in the context of tumor progression and the outgrowth of blood and
      lymphatic vessels. Here, we have developed an improved chemical synthesis for DEL
      in order to study the effects of the aglycon and its degradation product gallic
      acid (GA) on endothelial and tumor cells in vitro and in vivo. We found that DEL
      blocked the proliferation in vitro of primary human blood and lymphatic
      endothelial cells as well as human HT29 colon and rat MT-450 mammary carcinoma
      cells in a dose-dependent manner. In contrast, its degradation product GA had
      little effect. At higher concentrations, DEL induced apoptosis of endothelial and
      tumor cells. Furthermore, DEL potently blocked the outgrowth of lymphatic
      capillaries in ex vivo lymphangiogenesis assays. In the MT-450 rat syngeneic
      breast tumor model, it also significantly reduced angiogenesis and tumor-induced
      lymphangiogenesis when administered in vivo. These data reveal DEL to be a novel
      antilymphangiogenesis reagent. Surprisingly, however, the application of DEL
      unexpectedly promoted tumor growth and metastasis in the MT-450 tumor model,
      suggesting that the antiproliferative effect of DEL on cultured cells does not
      necessarily reflect the response of tumors to this anthocyanidin in vivo.
      Furthermore, while DEL may have utility as a cancer chemopreventative agent, its
      ability to promote tumor growth once a neoplasm develops also needs to be taken
      into consideration. 

PMID- 23975833
TI  - Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) promotes
      glioblastoma cell chemotaxis via Lyn activation.
AB  - The long-term survival of patients with glioblastoma is compromised by the
      proclivity for local invasion into the surrounding normal brain, escaping
      surgical resection and contributing to therapeutic resistance. Tumor necrosis
      factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis
      factor superfamily, can stimulate glioma cell invasion via binding to fibroblast
      growth factor-inducible 14 (Fn14) and subsequent activation of the Rho guanosine
      triphosphatase family member Rac1. Here, we demonstrate that TWEAK acts as a
      chemotactic factor for glioma cells, a potential process for driving cell
      invasion into the surrounding brain tissue. TWEAK exposure induced the activation
      of Src family kinases (SFKs), and pharmacologic suppression of SFK activity
      inhibited TWEAK-induced chemotactic migration. We employed a multiplexed Luminex
      assay and identified Lyn as a candidate SFK activated by TWEAK. Depletion of Lyn
      suppressed TWEAK-induced chemotaxis and Rac1 activity. Furthermore, Lyn gene
      expression levels increase with primary glioma tumor grade and inversely
      correlate with patient survival. These results show that TWEAK-induced glioma
      cell chemotaxis is dependent upon Lyn kinase function and, thus, provides
      opportunities for therapeutic targeting of this deadly disease. 

PMID- 23975835
TI  - Female-specific rectal carcinogenesis in cyclin D1b transgenic mice.
AB  - Human cyclin D1 generates two major isoforms via alternative splicing: cyclin D1a
      and cyclin D1b. Cyclin D1b is hardly expressed in normal tissues but is
      frequently expressed in certain types of cancer tissues. To clarify the oncogenic
      potential of cyclin D1b variant, we developed cyclin D1b transgenic (Tg) mice and
      analyzed their phenotypes. We detected rectal tumors in 63% (15/24) of the female
      Tg mice. All rectal tumors had the histological characteristics similar to human
      sessile serrated adenoma/polyps (SSA/Ps). Adenocarcinomas were also found in 53%
      (8/15) of the rectal tumors, suggesting that these adenocarcinomas originated
      from the SSA/P-like lesions. No rectal tumors were found in the ovariectomized
      female cyclin D1b Tg mice (0/10), indicating that ovarian hormones played a
      critical role in rectal carcinogenesis in these Tg mice. Both phosphorylation of
      Erk, without activating MEK, and expression of estrogen receptor beta were
      elevated in the rectal tumors of female cyclin D1b Tg mice compared with normal
      rectums of female wild-type mice. In addition, we established a cell line,
      D1bTgRT, derived from a rectal cancer of female Tg mouse. Small interfering RNA
      induced cyclin D1b knockdown in this cell line suppressed Erk phosphorylation,
      anchorage-independent growth, cell invasiveness and tumorigenicity in nude mice.
      In humans, expression of cyclin D1b messenger RNA was detected in 17% (1/6) of
      colorectal cancer cell lines and 9.7% (3/31) of colorectal cancer tissues. Taken
      together, these results indicate that cyclin D1b expression contributes to the
      female- specific rectal carcinogenesis in mouse model. 

PMID- 23975836
TI  - Genetic evidence for polygynandry in the black-striped pipefish Syngnathus
      abaster: a microsatellite-based parentage analysis.
AB  - Sexual selection theory predicts that, in organisms with reversed sex roles, more
      polyandrous species exhibit higher levels of sexual dimorphism. In the family
      Syngnathidae (pipefish, seahorses, and seadragons), males provide all parental
      care by carrying developing embryos on their ventral surfaces, and females
      develop secondary sex characters. Syngnathids exhibit a variety of genetic mating
      patterns, making them an ideal group to test predictions of sexual selection
      theory. Here, we describe the mating system of the black-striped pipefish
      Syngnathus abaster, using 4 highly variable microsatellites to analyze parentage
      of 102 embryos. Results revealed that 1) both sexes mate multiple times over the
      course of a pregnancy (polygynandrous mating system), 2) eggs are spatially
      segregated by maternity within each brood pouch, and 3) larger females have
      higher mating success (Kolmogorov-Smirnov test; P < 0.05). Together with similar
      studies of other syngnathid species, our results support the hypothesis that the
      mating system is related to the intensity of sexual dimorphism. 

PMID- 23975837
TI  - Male killing caused by a Spiroplasma symbiont in the small brown planthopper,
      Laodelphax striatellus.
AB  - Spiroplasma-mediated late male killing was found in the small brown planthopper,
      Laodelphax striatellus. Female-biased colonies (maternal lines, N = 4) were
      established from planthoppers collected in Taiwan and Japan. This sex ratio
      distortion was maternally inherited (sex ratio of total number of progenies
      [female:male]: 488:0 in F1, 198:7 in F2, 407:0 in F3; likelihood ratio test of
      all generations, P < 0.0001) and caused by male death during nymphal stages. The
      female-biased colonies were doubly infected with Spiroplasma and Wolbachia, and
      the non-biased colonies were infected solely with Wolbachia. Antibiotic treatment
      resulted in a normal sex ratio, strongly suggesting that bacteria are
      manipulating host reproduction. Spiroplasma-singly-infected planthopper colonies
      created by the antibiotic treatment produced progeny with strongly female-biased
      sex ratios (181:2; likelihood ratio test, chi(2) = 231.6, P < 0.0001). This is
      the first report of Spiroplasma-mediated male killing in hemimetabolous insects. 

PMID- 23975838
TI  - The value of repeat biopsy in the management of lupus nephritis: an international
      multicentre study in a large cohort of patients.
AB  - BACKGROUND: The International Society of Nephrology/Renal Pathology Society
      (ISN/RPS) classification represents the gold standard for the histological
      evaluation of Systemic Lupus Erythematosus (SLE) nephritis. A repeat biopsy (RB)
      might be an important tool to provide information on long-term renal outcomes and
      optimal therapy. Aims of this study were to evaluate the use of the ISN/RPS
      classification and the role of RB in routine clinical practice. METHODS: A total
      number of 142 patients with SLE nephritis and with adequate reference and RB
      samples were included in this multicentre retrospective study. A meticulous
      histological examination was centrally performed on first and RB and compared
      with clinical variables and follow-up data. RESULTS: Morphological features of
      the ISN/RPS classification: at first and RB, significant differences were
      observed between segmental classes (III, IV-S) and Class IV-G in mesangial
      proliferation, wire loops and tuft necrosis. Clinical features and ISN/RPS
      classification: the correlation between serum creatinine, proteinuria, blood
      pressure levels and histological classes at first and RB demonstrated more severe
      renal disease in Class IV-G, both at first and RB. Agreement between ISN/RPS
      classification at first and RB: 40.8% of patients changed the histological class.
      Fifty per cent of Class II (mild mesangial form) were reclassified as Class IV-G
      at RB, whereas 18.9% of Class IV-G were reclassified as Class II. The transition
      among segmental (III/IV-S) and mesangial forms (II/IV-G) was extremely rare. The
      comparison between the clinical parameters at the final follow-up and the ISN/RPS
      classification confirmed that the trend of serum creatinine and proteinuria
      between the different classes was better described at the RB (higher in Class IV
      G) than on the first biopsy. CONCLUSIONS: The histopathological data suggest that
      morphological differences between segmental and global forms do exist, possibly
      due to different pathogenetic mechanisms. An RB strategy could provide additional
      information on long-term renal outcomes. A strategy of protocol biopsies could be
      useful in perspective future trials to better understand the therapeutic response
      and the natural history of this disease.

PMID- 23975840
TI  - Diagnosis of obesity in chronic kidney disease: BMI or body fat?

PMID- 23975839
TI  - Serum hepatocyte growth factor is associated with truncal fat mass and increased
      mortality in chronic kidney disease stage 5 patients with protein-energy wasting.
AB  - BACKGROUND: Obese sarcopenia characterized by increased fat mass and protein
      energy wasting (PEW) is not uncommon in chronic kidney disease (CKD) stage 5
      patients in whom it is associated with worse outcomes. Serum hepatocyte growth
      factor (HGF) is associated with obesity in the general population and is
      increased in CKD patients in whom its association with body composition is not
      known. We studied the associations between HGF, PEW and body composition, and
      between HGF and mortality, in CKD stage 5 patients starting dialysis. METHODS: In
      224 CKD stage 5 patients (139 males, mean age 52 years, mean glomerular
      filtration rate (GFR) 6.6 mL/min), blood samples were obtained for analyses of
      HGF, high-sensitivity C-reactive protein (hsCRP), glucose, insulin and lipids.
      Total fat mass index (FMI), truncal fat mass index (TFMI) and lean body mass
      index (LBMI) assessed by dual-energy X-ray absorptiometry and PEW assessed by
      subjective global assessment (SGA) were recorded at baseline. Patients were
      followed up for 5 years. RESULTS: Serum HGF levels were higher in patients with
      high TFMI versus low TFMI [3.1 (IQR: 2.4-4.5) versus 2.7 (IQR: 1.9-3.8) ng/mL; P
      = 0.01] and in those with PEW versus non-PEW [3.4 (IQR: 2.4-3.6) versus 2.8 (IQR:
      2.1-3.8) ng/mL; P = 0.03]. Patients with both high TFMI and presence of PEW had
      significantly (P < 0.001) higher HGF concentration [4.4 (IQR: 3.3-6.6) ng/mL]
      than other patient groups (high TFMI and non-PEW, low TFMI and PEW or low TFMI
      and non-PEW). Multivariate linear regression showed that TFMI was an independent
      predictor of HGF (R(2) = 0.21, P = 0.048). In Cox analysis, patients with high
      HGF and presence of PEW had worse all-cause mortality after adjusting for age,
      gender and hsCRP (HR: 3.59, 95% CI: 1.19-5.35). CONCLUSIONS: Increased TFMI was
      an independent predictor of HGF in CKD stage 5 patients. Moreover, an elevated
      HGF level increased the mortality risk in the presence of PEW. These results
      suggest a central role of HGF in the metabolic and nutritional alterations in CKD
      stage 5 patients.

PMID- 23975841
TI  - Increased risk of dialysis and end-stage renal disease among HIV patients in
      Denmark compared with the background population.
AB  - BACKGROUND: HIV patients have increased risk of impaired renal function. We aimed
      to estimate the incidence of any renal replacement therapy (aRRT) and start of
      chronic renal replacement therapy (cRRT) among HIV patients compared with
      population controls. METHODS: In a nationwide, population-based cohort study we
      analysed incidence rates (IR), incidence rate ratios (IRR) and risk factors for
      aRRT and cRRT among HIV patients compared with an age- and gender-matched
      population control cohort using Poisson regression. RESULTS: We identified 5300
      HIV patients and 53 000 population controls. The IRs per 10 000 person-years of
      aRRT and cRRT among HIV patients were 15.9 (95% CI: 12.5-20.1) and 4.4 (95% CI:
      2.8-6.9), respectively. The IRR was 4.7 (95% CI: 3.5-6.2) for aRRT and 3.6 (95%
      CI: 2.2-6.0) for cRRT compared with population controls. Risk of aRRT was
      increased during the first year after HIV diagnosis [IRR 3.5 (95% CI: 1.5-8.1)],
      after a diagnosis of AIDS [IRR 2.3 (95% CI: 1.3-3.9)], in intravenous drug users
      [IRR 6.0 (95% CI: 2.9-12.2)] and in patients with hypertension [IRR 7.0 (95% CI:
      3.7-13.2)]. Factors associated with increased risk of cRRT were hypertension [IRR
      20 (95% CI: 6.8-61)] and baseline eGFR < 60 mL/min pr. 1.73 m(2) [IRR 7.8 (95%
      CI: 1.2-50)]. Exposure to tenofovir and/or atazanavir was not associated with
      risk of aRRT or cRRT. CONCLUSIONS: The risk of aRRT is increased more than 4-fold
      and the risk of cRRT is increased more than 3-fold in HIV patients in Denmark
      compared with the background population. We found no association between exposure
      to tenofovir, atazanavir or the combination of the two and risk of aRRT or cRRT.

PMID- 23975842
TI  - The effect of cholecalciferol for lowering albuminuria in chronic kidney disease:
      a prospective controlled study.
AB  - BACKGROUND: Growing evidence indicates that vitamin D receptor activation may
      have antiproteinuric effects. We aimed to evaluate whether vitamin D
      supplementation with daily cholecalciferol could reduce albuminuria in
      proteinuric chronic kidney disease (CKD) patients. METHODS: This 6-month
      prospective, controlled, intervention study enrolled 101 non-dialysis CKD
      patients with albuminuria. Patients with low 25(OH) vitamin D [25(OH)D] and high
      parathyroid hormone (PTH) levels (n = 50; 49%) received oral cholecalciferol (666
      IU/day), whereas those without hyperparathyroidism (n = 51; 51%), independent of
      their vitamin D status, did not receive any cholecalciferol, and were considered
      as the control group. RESULTS: Cholecalciferol administration led to a rise in
      mean 25(OH)D levels by 53.0 +/- 41.6% (P < 0.001). Urinary albumin-to-creatinine
      ratio (uACR) decreased from (geometric mean with 95% confidence interval) 284
      (189-425) to 167 mg/g (105-266) at 6 months (P < 0.001) in the cholecalciferol
      group, and there was no change in the control group. Reduction in a uACR was
      observed in the absence of significant changes in other factors, which could
      affect proteinuria, like weight, blood pressure (BP) levels or antihypertensive
      treatment. Six-month changes in 25(OH)D levels were significantly and inversely
      associated with that in the uACR (Pearson's R = -0.519; P = 0.036), after
      adjustment by age, sex, body mass index, BP, glomerular filtration rate and
      antiproteinuric treatment. The mean PTH decreased by -13.8 +/- 20.3% (P = 0.039)
      only in treated patients, with a mild rise in phosphate and calcium-phosphate
      product [7.0 +/- 14.7% (P = 0.002) and 7.2 +/- 15.2% (P = 0.003), respectively].
      CONCLUSIONS: In addition to improving hyperparathyroidism, vitamin D
      supplementation with daily cholecalciferol had a beneficial effect in decreasing
      albuminuria with potential effects on delaying the progression of CKD.

PMID- 23975843
TI  - When do we need competing risks methods for survival analysis in nephrology?
AB  - Survival analyses are commonly applied to study death or other events of
      interest. In such analyses, so-called competing risks may form an important
      problem. A competing risk is an event that either hinders the observation of the
      event of interest or modifies the chance that this event occurs. For example,
      when studying death on dialysis, receiving a kidney transplant is an event that
      competes with the event of interest. Conventional methods for survival analysis
      ignoring the competing event(s), such as the Kaplan-Meier method and standard Cox
      proportional hazards regression, may be inappropriate in the presence of
      competing risks, and alternative methods specifically designed for analysing
      competing risks data should then be applied. This problem deserves more attention
      in nephrology research and in the current article, we therefore explain the
      problem of competing risks in survival analysis and how using different
      techniques may affect study results. 

PMID- 23975844
TI  - Clinical Aspects of Huntington's Disease.
AB  - Huntington's disease (HD) is a devastating inherited neurodegenerative condition
      characterized by progressive motor, cognitive, and psychiatric symptoms. Symptoms
      progress over 15-20 years, and there are currently no disease-modifying
      therapies. The causative genetic mutation is an expanded CAG repeat in the HTT
      gene encoding the Huntingtin protein, and is inherited in an autosomal dominant
      manner. In this chapter we discuss the genetics, clinical presentation, and
      management of this condition, as well as new data from large-scale clinical
      research studies on the natural history of HD. 

PMID- 23975846
TI  - [Appraisal, diagnosis and therapy of chronic metabolic acidosis in Germany].
AB  - BACKGROUND AND OBJECTIVE: Data concerning chronic metabolic acidosis (CMA) has
      been sparse for a long time. This might be one reason why the diagnosis and
      therapy of this common complication in CKD patients has not received much
      attention. Emerging clinical data indicate that the treatment of metabolic
      acidosis, which is simple and cost-efficient, offers great therapeutic potential.
      PATIENTS AND METHODS: Survey among German nephrologists to collect information
      about current appraisal, diagnostic and therapeutic routine in clinical practice,
      and to determine the need for recommendations by the medical society. RESULTS: In
      August 2012, all nephrologists in Germany (n = 2095) were asked to complete a
      standardized questionnaire regarding diagnosis, evaluation and therapy of CMA.
      207 questionnaires (9.9 %) were returned and analysed. The CMA was rated as the
      second most important contributor for the progression of renal insufficiency,
      with the most important being hypertension. In addition, there was a high
      consensus concerning diagnosis and therapy of CMA. But estimates on prevalence
      were highly diverse. CONCLUSION: In this survey the CMA was rated as an important
      co-morbidity. Participating nephrologists mostly followed treatment guidelines.
      However, major differences in the perception of prevalence of CMA were observed,
      leaving the possibility that CMA is still underdiagnosed. Further recommendations
      of the German Society of Nephrology could improve the diagnosis and therapy.

PMID- 23975847
TI  - The blood glucose-lowering effect of racecadotril is not attributable to
      inhibition of insulin-degrading enzyme.

PMID- 23975848
TI  - Prognostic marker for liver disease due to alpha1-antitrypsin deficiency.
AB  - BACKGROUND: Only some Alpha1-antitrypsin deficiency (A1ATD) PiZZ patients develop
      liver cirrhosis and portal hypertension. Aim of the study was to investigate the
      course of liver disease associated with PiZZ A1ATD and to determine prognostic
      factors. PATIENTS: We retrospectively reviewed the clinical and laboratory data
      of all PiZZ children up to 18 years of age admitted to our centre since 1978. 53
      patients (age at first visit 2 days to 12 years) met our criteria. METHODS: The
      children were divided into 2 groups: group 1 'bad prognosis', meaning the
      patients which were on the waiting list for liver transplantation (LTx), had a
      liver transplantation or had died, and group 2 'good prognosis', containing the
      patients they were living with their own liver. We analysed family history
      including smoking, gestational age, maternal age at delivery, date of birth, sex,
      neonatal history, breast-feeding, symptoms at presentation, clinical and
      laboratory data and date of LTx and/or death. RESULTS: Various anamnesis
      parameters such as manifestation of neonatal cholestasis showed no prognostic
      significance. In contrast the laboratory parameters thrombocytes (p=0.008),
      bilirubin (p<0.001), prothrombin time (p<0.001), choline-sterase (p<0.001), gamma
      GT (p=0.001) and GOT (p=0.002) showed a correlation with a liver transplantation
      and/or death. CONCLUSION: Prognosis is difficult to determine at an early stage
      of this disease, but various laboratory parameters can help to predict an
      outcome. Therefore a regular follow-up is necessary for the children.

PMID- 23975849
TI  - [Legal consequences in cases of child abuse].
AB  - Medical child protection includes besides interdisciplinary diagnostics and
      treatment of physical and psychological symptoms also a discussion that looks at
      the ensuing legal consequences.This study analyses 21 criminally investigated
      cases of suspected child abuse from a 2 year study period and compares severity
      of injury to legal outcome.7 of those 21 criminal proceedings were already
      dropped by the prosecution and never went to trial. 4 of the 8 cases that led to
      a trial ended with a conviction. In all of the 4 cases that resulted in an
      acquittal the judges had been convinced that the child had been abused but found
      themselves unable to exactly identify the perpetrator. Our study's cases did not
      show a positive correlation between severity of injury and legal
      outcome.Diagnosing and treating children and minors within the context of medical
      child protection should always also include the ques-tion of possible legal
      consequences. The judicial process in cases of serious child abuse requires high
      medical expertise. Such expertise particularly includes the ability to determine
      the time of injury as exactly as possible and to provide precise written
      documentation of any medical findings. However, our study also shows that medical
      assessment is only one of many aspects in the legal response to child abuse. 

PMID- 23975845
TI  - Neurobiology of schizophrenia onset.
AB  - The clinical symptoms and cognitive and functional deficits of schizophrenia
      typically begin to gradually emerge during late adolescence and early adulthood.
      Recent findings suggest that disturbances of a specific subset of inhibitory
      neurons that contain the calcium-binding protein parvalbumin (PV), which may
      regulate the course of postnatal developmental experience-dependent synaptic
      plasticity in the cerebral cortex, including the prefrontal cortex (PFC), may be
      involved in the pathogenesis of the onset of this illness. Specifically,
      converging lines of evidence suggest that oxidative stress, extracellular matrix
      (ECM) deficit and impaired glutamatergic innervation may contribute to the
      functional impairment of PV neurons, which may then lead to aberrant
      developmental synaptic pruning of pyramidal cell circuits during adolescence in
      the PFC. In addition to promoting the functional integrity of PV neurons,
      maturation of ECM may also play an instrumental role in the termination of
      developmental PFC synaptic pruning; thus, ECM deficit can directly lead to
      excessive loss of synapses by prolonging the course of pruning. Together, these
      mechanisms may contribute to the onset of schizophrenia by compromising the
      integrity, stability, and fidelity of PFC connectional architecture that is
      necessary for reliable and predictable information processing. As such, further
      characterization of these mechanisms will have implications for the
      conceptualization of rational strategies for the diagnosis, early intervention,
      and prevention of this debilitating disorder. 

PMID- 23975850
TI  - Venous thromboembolism in adolescents associated with drospirenone-containing
      oral contraceptives - two case reports.

PMID- 23975851
TI  - Cysteine-rich protein 2 alters p130Cas localization and inhibits vascular smooth
      muscle cell migration.
AB  - AIMS: Cysteine-rich protein (CRP) 2, a member of the LIM-only CRP family that
      contains two LIM domains, is expressed in vascular smooth muscle cells (VSMCs) of
      blood vessels and functions to repress VSMC migration and vascular remodelling.
      The goal of this study was to define the molecular mechanisms by which CRP2
      regulates VSMC migration. METHODS AND RESULTS: Transfection of VSMCs with CRP2
      EGFP constructs revealed that CRP2 associated with the actin cytoskeleton. In
      response to chemoattractant stimulation, Csrp2 (mouse CRP2 gene symbol)-deficient
      (Csrp2(-/-)) VSMCs exhibited increased lamellipodia formation. Re-introduction of
      CRP2 abrogated the enhanced lamellipodia formation and migration of Csrp2(-/-)
      VSMCs following chemoattractant stimulation. Mammalian 2-hybrid and co
      immunoprecipitation assays demonstrated that CRP2 interacts with p130Cas, a
      scaffold protein important for lamellipodia formation and cell motility.
      Immunofluorescence staining showed that CRP2 colocalized with phospho-p130Cas at
      focal adhesions (FAs)/terminal ends of stress fibres in non-migrating cells.
      Interestingly, in migrating cells phospho-p130Cas localized to the leading edge
      of lamellipodia and FAs, whereas CRP2 was restricted to FAs and stress fibres.
      Furthermore, we demonstrated that p130Cas expression and phosphorylation promote
      neointima formation following arterial injury. CONCLUSION: These studies
      demonstrate that CRP2 sequesters p130Cas at FAs, thereby reducing lamellipodia
      formation and blunting VSMC migration.

PMID- 23975852
TI  - The galectin-3/RAGE dyad modulates vascular osteogenesis in atherosclerosis.
AB  - AIMS: Vascular calcification correlates with inflammation and plaque instability
      in a dual manner, depending on the spotty/granular (micro) or sheet
      like/lamellated (macro) pattern of calcification. Modified lipoproteins trigger
      both inflammation and calcification via receptors for advanced
      lipoxidation/glycation endproducts (ALEs/AGEs). This study compared the roles of
      galectin-3 and receptor for AGEs (RAGE), two ALEs/AGEs-receptors with diverging
      effects on inflammation and bone metabolism, in the process of vascular
      calcification. METHODS AND RESULTS: We evaluated galectin-3 and RAGE
      expression/localization in 62 human carotid plaques and its relation to
      calcification pattern, plaque phenotype, and markers of inflammation and vascular
      osteogenesis; and the effect of galectin-3 ablation and/or exposure to an ALE/AGE
      on vascular smooth muscle cell (VSMC) osteogenic differentiation. While RAGE co
      localized with inflammatory cells in unstable regions with microcalcification,
      galectin-3 was expressed also by VSMCs, especially in macrocalcified areas, where
      it co-localized with alkaline phosphatase. Expression of galectin-3 and
      osteogenic markers was higher in macrocalcified plaques, whereas the opposite
      occurred for RAGE and inflammatory markers. Galectin-3-deficient VSMCs exhibited
      defective osteogenic differentiation, as shown by altered expression of
      osteogenic transcription factors and proteins, blunted activation of pro
      osteoblastogenic Wnt/beta-catenin signalling and proliferation, enhanced
      apoptosis, and disorganized mineralization. These abnormalities were associated
      with RAGE up-regulation, but were only in part prevented by RAGE silencing, and
      were partially mimicked or exacerbated by treatment with an AGE/ALE. CONCLUSION:
      These data indicate a novel molecular mechanism by which galectin-3 and RAGE
      modulate in divergent ways, not only inflammation, but also vascular
      osteogenesis, by modulating Wnt/beta-catenin signalling, and independently of
      ALEs/AGEs.

PMID- 23975853
TI  - In memoriam: Seymour Lieberman, hormonologist, chemist and humanist (1916-2012);
      National Academy of Sciences of the United States of America, member, and
      Endocrine Society, president, 1974-1975.

PMID- 23975854
TI  - News and views: at long last, an animal model of Graves' orbitopathy.

PMID- 23975855
TI  - Salivary alpha-amylase and cortisol responsiveness following electrical
      stimulation stress in patients with the generalized type of social anxiety
      disorder.
AB  - INTRODUCTION: Social anxiety disorder is believed to be a stress-induced disease.
      Although it can be inferred from the symptoms during attacks that there exists
      some abnormality of autonomic nervous system in any of the stress systems in
      social anxiety disorder, little evidence has been reported. This study focused on
      comparing the reactivity of 2 stress systems, the autonomic nervous system (ANS)
      and the hypothalamic-pituitary-adrenal (HPA) axis in patients with social anxiety
      disorder. METHODS: 32 patients with the generalized type of social anxiety
      disorder were compared with 80 age- and gender-matched controls. We collected
      saliva samples from patients and controls before and after electrical stimulation
      to measure the concentrations of salivary alpha-amylase (sAA) and salivary
      cortisol. Profile of Mood State (POMS) and State-Trait Anxiety Inventory (STAI)
      scores and Heart Rate Variability (HRV) were also determined following
      stimulation. RESULTS: SAA in patients displayed a significantly higher level at
      baseline and a significantly larger response to electrical stimulation as
      compared to controls, whereas no group differences were seen in any HRV. Neither
      within-subject nor group differences were seen in salivary cortisol levels.
      CONCLUSIONS: These results suggest that SAD patients displayed enhanced ANS (but
      not HPA axis) activity vs. healthy controls.

PMID- 23975856
TI  - Short-term effects of radiofrequency shrinkage treatment for anterior cruciate
      ligament relaxation on proprioception.
AB  - OBJECTIVE: Radiofrequency (RF) shrinkage is used in anterior cruciate ligament
      (ACL) reconstruction. The present study investigated the therapeutic effects of
      RF on ACL relaxation and the probable influencing factors. METHODS: Patients with
      ACL relaxation were included. Participants were randomly divided into two groups:
      a treatment group, in which patients were treated with RF shrinkage (RF group); a
      control group, in which patients received conventional surgical treatment.
      Thermal shrinkage was performed on ACL using an ArthroCare(r) CAPSure(r) wand.
      Lysholm scores, proprioceptive testing and Tegner activity scores were evaluated
      before and after treatment (at 6 and 12 months). RESULTS: A total of 38 patients
      were included. The mean +/- SD Lysholm score of those in the RF group at 12
      months' post-treatment was significantly higher than in controls. The angle of
      deviation of the knee joint in RF group was significantly larger than in the
      control group at 6 months' post-treatment. CONCLUSIONS: RF shrinkage treatment
      for ACL laxity could improve knee scores, and may affect proprioception and
      recovery of activity after surgery.

PMID- 23975857
TI  - Disease-modifying effect of etanercept versus sulphasalazine on spinal mobility
      in patients with ankylosing spondylitis.
AB  - OBJECTIVE: To model the estimated disease-modifying effect of etanercept over
      sulphasalazine in patients with ankylosing spondylitis. METHODS: A post hoc
      analysis of data from the Ankylosing Spondylitis Study Comparing ENbrel and
      Sulfasalazine Dosed Weekly (ASCEND) study was performed using the Natural History
      Staggered Start (NHSS) method. A mixed model with a linear effect over time was
      fitted to the ASCEND data and resampling was performed to generate confidence
      intervals. RESULTS: At week 16, the total additional improvement in Bath
      Ankylosing Spondylitis Metrology Index of the etanercept arm over the
      sulphasalazine arm was 0.62 points, of which 31% (0.19 points) was estimated to
      be due to disease-modifying effect. CONCLUSIONS: The analysis of ASCEND data
      suggests that etanercept may have a larger disease-modifying effect than
      sulphasalazine. Further research is needed with more objective measures such as
      magnetic resonance imaging or X-radiography to confirm these results.

PMID- 23975858
TI  - The relationship between KRAS gene mutations and HLA class I antigen
      downregulation in the metastasis of non-small cell lung cancer.
AB  - OBJECTIVE: To investigate the association between v-Ki-ras2 Kirsten rat sarcoma
      viral oncogene homologue (KRAS) gene mutations and levels of human leucocyte
      antigen (HLA) class I antigen in primary lung tumours and metastatic lymph nodes
      of patients with non-small cell lung cancer (NSCLC). METHODS: Patients with NSCLC
      undergoing tumour resection were enrolled. KRAS codon 12 mutations were analysed
      in normal lung and lymph node tissue, primary lung tumours and metastatic lymph
      nodes using polymerase chain reaction-restriction fragment length polymorphism
      analysis. HLA class I antigen immunostaining was examined using flow cytometry.
      RESULTS: A total of 65 patients participated in the study. All normal lung
      tissues had positive HLA class I antigen immunostaining. The majority of primary
      lung tumours (56/65) and all of the metastatic lymph nodes (31/31) had
      downregulated HLA class I antigen immunostaining. There was a positive
      correlation between downregulated HLA class I antigen in primary tumours and
      metastatic lymph nodes. There was a negative correlation between KRAS codon 12
      mutations and the level of HLA class I antigen in primary and metastatic tumours.
      CONCLUSIONS: KRAS codon 12 mutations appear to be important in the downregulation
      of HLA class I antigen in NSCLC. Abnormal activation of the oncogenic KRAS
      pathway might provide a new treatment target for NSCLC.

PMID- 23975859
TI  - Bortezomib induces apoptosis and autophagy in osteosarcoma cells through mitogen
      activated protein kinase pathway in vitro.
AB  - OBJECTIVE: To investigate the effects of bortezomib on human osteosarcoma cells
      from the HOS cell line, and the underlying associated mechanisms. METHODS:
      Viability of HOS cells treated with bortezomib (5-20 nM) for different time
      periods was measured and changes in the cell cycle were assessed. Apoptosis and
      autophagy in HOS cells treated with bortezomib were analysed using annexin V
      fluorescein isothiocyanate assay, transmission electron microscopy and Western
      blotting. Surges in mitogen-activated protein kinase (MAPK) pathways including
      MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK1/2), ERK1/2, c-Jun N
      terminal kinase (JNK) and p38 MAPK were analysed using Western blotting. RESULTS:
      Bortezomib induced growth inhibition in a time- and dose-dependent manner, and
      autophagy and apoptosis in a dose-dependent manner, in HOS cells. HOS cell
      autophagy and apoptosis in response to bortezomib, corresponded with changing
      levels of intracellular MAPK signalling molecules. CONCLUSIONS: This study
      provided new insights into the mechanisms underlying bortezomib-induced apoptosis
      in human osteosarcoma HOS cells, and suggests that bortezomib could be a potent
      chemotherapeutic agent in the treatment of osteosarcoma.

PMID- 23975860
TI  - Pharmacist-led medication education in cancer pain control: a multicentre
      randomized controlled study in Guangzhou, China.
AB  - OBJECTIVE: To evaluate clinical pharmacist-led pain-medication education in
      patients with cancer. METHODS: A controlled study was conducted prospectively at
      six tertiary hospitals in China. In-patients with cancer were randomized to
      receive conventional treatment plus medication education or no education
      (controls). Education consisted of access to information booklets and eight 30
      min face-to-face counselling sessions given by clinical pharmacists over 4 weeks.
      Patients completed pain- and analgesic-knowledge assessments and a Brief Pain
      Inventory, pre- and post-study. RESULTS: A total of 123 and 114 patients in the
      education and control groups, respectively, completed follow-up. At the end of
      the study, patient knowledge regarding cancer pain and pain control was
      significantly increased in both groups; pain and analgesic knowledge scores were
      significantly higher in the education group compared with controls. In the
      control group, the increase in total pain-related knowledge was significantly
      greater in analgesic-naive patients compared with those who were using/had used
      analgesics. Pain intensity scores and pain interference of daily activities were
      significantly reduced in the education group compared with controls. CONCLUSIONS:
      Clinical pharmacist-led medication education resulted in improved pain control in
      patients with cancer.

PMID- 23975861
TI  - Distorted secretory granule composition in mast cells with multiple protease
      deficiency.
AB  - Mast cells are characterized by an abundance of secretory granules densely packed
      with inflammatory mediators such as bioactive amines, cytokines, serglycin
      proteoglycans with negatively charged glycosaminoglycan side chains of either
      heparin or chondroitin sulfate type, and large amounts of positively charged
      proteases. Despite the large biological impact of mast cell granules and their
      contents on various pathologies, the mechanisms that regulate granule composition
      are incompletely understood. In this study, we hypothesized that granule
      composition is dependent on a dynamic electrostatic interrelationship between
      different granule compounds. As a tool to evaluate this possibility, we generated
      mice in which mast cells are multideficient in a panel of positively charged
      proteases: the chymase mouse mast cell protease-4, the tryptase mouse mast cell
      protease-6, and carboxypeptidase A3. Through a posttranslational effect, mast
      cells from these mice additionally lack mouse mast cell protease-5 protein. Mast
      cells from mice deficient in individual proteases showed normal morphology. In
      contrast, mast cells with combined protease deficiency displayed a profound
      distortion of granule integrity, as seen both by conventional morphological
      criteria and by transmission electron microscopy. An assessment of granule
      content revealed that the distorted granule integrity in multiprotease-deficient
      mast cells was associated with a profound reduction of highly negatively charged
      heparin, whereas no reduction in chondroitin sulfate storage was observed. Taken
      together with previous findings showing that the storage of basic proteases
      conversely is regulated by anionic proteoglycans, these data suggest that
      secretory granule composition in mast cells is dependent on a dynamic
      interrelationship between granule compounds of opposite electrical charge. 

PMID- 23975862
TI  - ASC controls IFN-gamma levels in an IL-18-dependent manner in caspase-1-deficient
      mice infected with Francisella novicida.
AB  - The inflammasome is a signaling platform that is central to the innate immune
      responses to bacterial infections. Francisella tularensis is a bacterium
      replicating within the host cytosol. During F. tularensis subspecies novicida
      infection, AIM2, an inflammasome receptor sensing cytosolic DNA, activates
      caspase-1 in an ASC-dependent manner, leading to both pyroptosis and release of
      the proinflammatory cytokines IL-1beta and IL-18. Activation of this canonical
      inflammasome pathway is key to limit F. novicida infection. In this study, by
      comparing the immune responses of AIM2 knockout (KO), ASC(KO), and Casp1(KO) mice
      in response to F. novicida infection, we observed that IFN-gamma levels in the
      serum of Casp1(KO) mice were much higher than the levels observed in AIM2(KO) and
      ASC(KO) mice. This difference in IFN-gamma production was due to a large
      production of IFN-gamma by NK cells in Casp1(KO) mice that was not observed in
      ASC(KO) mice. The deficit in IFN-gamma production observed in ASC(KO) mice was
      not due to a reduced Dock2 expression or to an intrinsic defect of ASC(KO) NK
      cells. We demonstrate that in infected Casp1(KO) mice, IFN-gamma production is
      due to an ASC-dependent caspase-1-independent pathway generating IL-18.
      Furthermore, we present in vitro data suggesting that the recently described
      AIM2/ASC/caspase-8 noncanonical pathway is responsible for the caspase-1
      independent IL-18 releasing activity. To our knowledge, this study is the first
      in vivo evidence of an alternative pathway able to generate in a caspase-1
      independent pathway bioactive IL-18 to boost the production of IFN-gamma, a
      cytokine critical for the host antibacterial response. 

PMID- 23975864
TI  - Expression of the immune regulator tripartite-motif 21 is controlled by IFN
      regulatory factors.
AB  - Tripartite-motif 21 (TRIM21) is an E3 ubiquitin ligase that regulates innate
      immune responses by ubiquitinating IFN regulatory factors (IRFs). TRIM21 is
      mainly found in hematopoietic cells in which its expression is induced by IFNs
      during viral. infections and in systemic autoimmune diseases such as systemic
      lupus erythematosus and Sjogren's syndrome. However, the exact molecular
      mechanism by which the expression of the Trim21 gene is regulated is unknown. In
      this study, we demonstrate that IFNs induce Trim21 expression in immune cells via
      IRFs and that IFN-alpha and IFN-beta are the most potent inducers of Trim21. A
      functional IFN-stimulated response element but no conserved IFN-gamma-activated
      site was detected in the promoter of Trim21. IRF1 and IRF2 strongly induced
      Trim21 expression in an IFN-stimulated response element-dependent manner, whereas
      IRF4 and IRF8 strongly repressed the IRF1-mediated induction of Trim21.
      Consistent with this observation, baseline expression of Trim21 was elevated in
      Irf4(-/-) cells. TRIM21, IRF1, and IRF2 expression was increased in PBMCs from
      patients with Sjogren's syndrome compared with healthy controls. In contrast,
      IRF4 and IRF8 expression was not increased in PBMCs from patients. The IFN-gamma
      mediated induction of Trim21 was completely abolished by inhibiting protein
      synthesis with cycloheximide, and Trim21 expression could not be induced by IFN
      gamma in Irf1(-/-) cells, demonstrating that IFN-gamma induces Trim21 indirectly
      via IRF1 and not directly via STAT1 activation. Our data demonstrate that
      multiple IRFs tightly regulate expression of Trim21 in immune cells, suggesting
      that a well-controlled expression of the E3 ligase TRIM21 is important for
      regulation of immune responses. 

PMID- 23975865
TI  - Parasite infections in multiple sclerosis modulate immune responses through a
      retinoic acid-dependent pathway.
AB  - We recently demonstrated better outcomes in helminth-infected multiple sclerosis
      (MS) patients, compared with uninfected ones. The present study evaluates the
      role of TLR2 and retinoic acid (RA) in parasite-driven protection in MS patients.
      RA serum levels were significantly higher in helminth-infected MS patients than
      in uninfected MS subjects or healthy controls. Genes involved in RA biosynthesis
      and metabolism, such as Adh1 and Raldh2, as well as RA receptors and IL-10, were
      induced in dendritic cells (DCs) via TLR2-dependent ERK signaling. This
      programmed DCs to induce FOXP3(+) T regulatory cells and suppressed production of
      proinflammatory cytokines (IL-6, IL-12, IL-23, and TNF-alpha) via induction of
      suppressor of cytokine signaling 3 (SOCS3), an effect mediated by soluble egg Ag
      (SEA) obtained from Schistosoma mansoni, and by RA. SEA-activated DCs also
      inhibited IL-17 and IFN-gamma production through autoreactive T cells. These
      inhibitory effects were abrogated when SOCS3 gene expression was silenced,
      indicating that SEA-mediated signaling inhibited production of these cytokines by
      T cells, through a SOCS3-dependent pathway. Overall, helminth-related
      immunomodulation observed in MS patients was mediated by TLR2- and RA-dependent
      pathways, through two different mechanisms, as follows: 1) induction of IL-10 and
      FOXP3(+) T regulatory cells, and 2) suppression of proinflammatory cytokine
      production mediated by SOCS3. 

PMID- 23975863
TI  - Modulation of inflammasome-mediated pulmonary immune activation by type I IFNs
      protects bone marrow homeostasis during systemic responses to Pneumocystis lung
      infection.
AB  - Although acquired bone marrow failure (BMF) is considered a T cell-mediated
      autoimmune disease, possible innate immune defects as a cause for systemic immune
      deviations in response to otherwise innocuous infections have not been
      extensively explored. In this regard, we recently demonstrated an important role
      of type I IFNs in protecting hematopoiesis during systemic stress responses to
      the opportunistic fungal pathogen Pneumocystis in lymphocyte-deficient mice. Mice
      deficient in both lymphocytes and type I IFN receptor (IFrag(-/-) mice) develop
      rapidly progressing BMF due to accelerated bone marrow (BM) cell apoptosis
      associated with innate immune deviations in the BM in response to Pneumocystis
      lung infection. However, the communication pathway between lung and BM eliciting
      the induction of BMF in response to this strictly pulmonary infection has been
      unclear. In this study, we report that absence of an intact type I IFN system
      during Pneumocystis lung infection not only causes BMF in lymphocyte-deficient
      mice but also transient BM stress in lymphocyte-competent mice. This is
      associated with an exuberant systemic IFN-gamma response. IFN-gamma
      neutralization prevented Pneumocystis lung infection-induced BM depression in
      type I IFN receptor-deficient mice and prolonged neutrophil survival time in BM
      from IFrag(-/-) mice. IL-1beta and upstream regulators of IFN-gamma, IL-12, and
      IL-18 were also upregulated in lung and serum of IFrag(-/-) mice. In conjunction,
      there was exuberant inflammasome-mediated caspase-1 activation in pulmonary
      innate immune cells required for processing of IL-18 and IL-1beta. Thus, absence
      of type I IFN signaling during Pneumocystis lung infection may result in
      deregulation of inflammasome-mediated pulmonary immune activation, causing
      systemic immune deviations triggering BMF in this model. 

PMID- 23975866
TI  - Characterization of the anxiolytic activity of Nunavik Rhodiola rosea.
AB  - Rhodiola rosea is a medicinal plant used by the indigenous Inuit people of
      Nunavik and Nunatsiavut, Eastern Canada, as a mental and physical rejuvenating
      agent. This traditional use led to the present investigation of R. rosea in the
      context of anxiety disorders. An alcohol extract of R. rosea roots was
      characterized phytochemically and orally administered for three consecutive days
      to Sprague-Dawley rats at 8 mg/kg, 25 mg/kg, and 75 mg/kg body weight. The rats
      were subjected to three behavioral paradigms of anxiety, including the elevated
      plus maze, social interaction, and contextual conditioned emotional response
      tests. Rhodiola rosea showed dose-dependent anxiolytic activity in the elevated
      plus maze and conditioned emotional response tests, with moderate effects in the
      higher-anxiety SI test. The active dose varied according to the anxiety test. In
      order to elucidate a mechanism, the extract was further tested in an in vitro
      GABAA-benzodiazepine receptor-binding assay, where it demonstrated low activity.
      This study provides the first comparative assessment of the anxiolytic activity
      of Nunavik R. rosea in several behaviour models and suggests that anxiolytic
      effects may be primarily mediated via pathways other than the GABAA
      benzodiazepine site of the GABAA receptor.

PMID- 23975867
TI  - Potentiating effect of glabridin on GABAA receptor-mediated responses in dorsal
      raphe neurons.
AB  - Flavonoid-rich ethanol extracts of licorice root have sedative and anxiolytic
      effects. Glabridin is a major flavonoid component from licorice which we
      evaluated by examining GABA responses in acutely isolated dorsal raphe neurons of
      the rat. Neurons were recorded with patch-clamp methods at a holding potential of
      - 50 mV. Glabridin potentiated GABA-induced responses by positively modulating
      GABAA receptor responses with different concentration range. GABA (2 * 10(-6) M)
      evoked currents were potentiated in a stepwise pattern increasing glabridin
      concentration. Between 10(-12) and 10(-8) M glabridin increased GABA responses by
      about 140 % of the control. At concentrations above 10(-7) M, a much larger, dose
      dependent potentiation occurred before reaching a plateau at 3 * 10-6 M
      glabridin. A hypnotic drug, zolpidem, also induced biphasic concentration
      potentiation relationship. The glabridin potentiation ratio was 2.2 times larger
      than the maximum potentiation to the benzodiazepine receptor full agonist
      diazepam. Benzodiazepine receptor antagonist, flumazenil (3 * 10(-7) M), failed
      to inhibit glabridin (3 * 10(-7) M)-induced potentiation. This result implies
      that glabridin may exhibit sedative and hypnotic effects by potentiating
      GABAergic inhibition in dorsal raphe neurons by GABAA receptor actions.

PMID- 23975868
TI  - Cat's claw oxindole alkaloid isomerization induced by cell incubation and
      cytotoxic activity against T24 and RT4 human bladder cancer cell lines.
AB  - The antitumor activity of Uncaria tomentosa, a native vine from the Amazonian
      rainforest, has been ascribed to pentacyclic oxindole alkaloids occurring in its
      bark. Former studies have shown that this activity, as well as its intensity,
      depends on whether cat's claw alkaloids occur as original compounds or isomerized
      derivatives. This work addresses this aspect, using T24 and RT4 human bladder
      cancer cell lines for that purpose. Bark samples were extracted by dynamic
      maceration, prepurified with cross-linked polyvinylpyrrolidone and properly
      fractioned by an ion exchange process to obtain an oxindole alkaloid purified
      fraction. Alkaloid isomerization was induced by heating it under reflux at 85 
      degrees C. Samples collected after 5, 15, and 45 min of heating were analyzed by
      HPLC-PDA, freeze-dried at once, and separately assayed using the non-isomerized
      purified fraction for comparison purposes. The latter showed significant and dose
      dependent cytotoxic activity against both T24 and RT4 cancer cell lines (IC50:
      164.13 and 137.23 ug/mL, respectively). However, results for both cell lines were
      equivalent to those observed for isomerized samples (p > 0.05). The alkaloid
      isomerization induced by the incubation conditions (buffered medium pH 7.4 and
      temperature 37  degrees C) helps to explain the similar results obtained from non
      isomerized and isomerized samples. Mitraphylline, speciophylline, uncarine F,
      and, to a lesser degree, pteropodine were more susceptible to isomerization under
      the incubation conditions. Thus, the alkaloid profile of all fractions and their
      cytotoxic activities against T24 and RT4 human bladder cancer cell lines are
      determined to a large extent by the incubation conditions.

PMID- 23975869
TI  - Triptolide downregulates Treg cells and the level of IL-10, TGF-beta, and VEGF in
      melanoma-bearing mice.
AB  - Regulatory T cells play a key role in suppressing tumor immunity. Triptolide, a
      major active component isolated from the Chinese medicinal herb Tripterygium
      wilfordii, has been proven to possess multiple antitumor activities. Here, we
      investigated the effect of triptolide on regulatory T cells and on the level of
      IL-10, transforming growth factor-beta, and vascular endothelial growth factor in
      tumor-bearing mice. Fifty male C57BL/6 mice were randomly grouped as follows:
      normal control group, model group with B16-F10 cells implanted, and three
      treatment groups with cyclophosphamide, triptolide-high dose, triptolide-low
      dose. The proportion of regulatory T cells in the spleen and axillary lymph nodes
      was evaluated by flow cytometric analysis. Production of cytokines IL-10,
      transforming growth factor-beta, and vascular endothelial growth factor in serum
      was measured using enzyme-labeled immunosorbent assay kits. The mRNA levels of
      Foxp3, IL-10, and transforming growth factor-beta in the spleen and vascular
      endothelial growth factor in tumor tissue were detected by real-time PCR. The
      results showed that triptolide significantly decreased the proportion of
      regulatory T cells and lowered the Foxp3 level in the spleen and axillary lymph
      nodes of tumor-bearing mice. Production of IL-10 and transforming growth factor
      beta in peripheral blood, and the mRNA level of IL-10 and transforming growth
      factor-beta in the spleen were also decreased. Additionally, triptolide could
      remarkably inhibit production of vascular endothelial growth factor in tumor
      bearing mice. In conclusion, our study demonstrated that triptolide might inhibit
      tumor growth by inhibiting regulatory T cells and some cytokines such as IL-10
      and transforming growth factor-beta, as well as production of vascular
      endothelial growth factor. 

PMID- 23975870
TI  - Is CGRP a marker for chronic migraine?

PMID- 23975871
TI  - Effect of chlorzoxazone in patients with downbeat nystagmus: a pilot trial.
AB  - OBJECTIVE: Downbeat nystagmus (DBN) is the most frequent form of acquired
      persisting fixation nystagmus with different symptoms such as unsteadiness of
      gait, postural instability, and blurred vision with reduced visual acuity (VA)
      and oscillopsia. However, different symptomatic therapeutic principles are
      required, such as 3,4-diaminopyridine and 4-aminopyridine, that effectively
      suppress DBN. Chlorzoxazone (CHZ) is a nonselective activator of small
      conductance calcium-activated potassium (SK) channels that modifies the activity
      of cerebellar Purkinje cells. We evaluated the effects of this agent on DBN in an
      observational proof-of-concept pilot study. METHODS: Ten patients received CHZ
      500 mg 3 times a day for 1 or 2 weeks. Slow-phase velocity of DBN, VA, postural
      sway, and the drug's side effects were evaluated. Recordings were conducted at
      baseline, 90 minutes after first administration, and after 1 or 2 weeks. RESULTS:
      Mean slow-phase velocity significantly decreased from a baseline of 2.74 degrees
      /s +/- 2.00 to 2.29 degrees /s +/- 2.12 (mean +/- SD) 90 minutes after first
      administration and to 2.04 degrees /s +/- 2.24 (p < 0.001; post hoc both p =
      0.024) after long-term treatment. VA significantly increased and postural sway in
      posturography showed a tendency to decrease on medication. Fifty percent of
      patients did not report any side effects. The most common reported side effect
      was abdominal discomfort and dizziness. CONCLUSIONS: The treatment with the SK
      channel activator CHZ is a potentially new therapeutic agent for the symptomatic
      treatment of DBN. CLASSIFICATION OF EVIDENCE: This study provides Class IV
      evidence that CHZ 500 mg 3 times a day may improve eye movements and visual
      fixation in patients with DBN.

PMID- 23975872
TI  - Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic
      migraine.
AB  - OBJECTIVE: To determine calcitonin gene-related peptide (CGRP) levels outside
      migraine attacks in peripheral blood as a potential biomarker for chronic
      migraine (CM). METHODS: Women older than 17 years and diagnosed with CM were
      recruited. Matched healthy women with no headache history and women with episodic
      migraine (EM) served as control groups, together with a series of patients with
      episodic cluster headache in a pain-free period. CGRP levels were determined in
      blood samples obtained from the right antecubital vein by ELISA outside a
      migraine attack and having taken no symptomatic medication the day before. For
      ethical reasons, preventatives were not stopped. RESULTS: We assessed plasma
      samples from 103 women with CM, 31 matched healthy women, 43 matched women with
      EM, and 14 patients with episodic cluster headache matched for age. CGRP levels
      were significantly increased in CM (74.90 pg/mL) as compared with control healthy
      women (33.74 pg/mL), women with EM (46.37 pg/mL), and patients with episodic
      cluster headache (45.87 pg/mL). Thresholds of 43.45 and 58.22 pg/mL optimize the
      sensitivity and specificity to differentiate CM from healthy controls and EM,
      respectively. In the CM group, CGRP levels were significantly increased in women
      with a history of migraine with aura vs those only experiencing migraine without
      aura. Variables such as age, analgesic overuse, depression, fibromyalgia,
      vascular risk factors, history of triptan consumption, or kind of preventative
      treatment did not significantly influence CGRP levels. CONCLUSION: Increased CGRP
      level measured in peripheral blood outside migraine attacks and in the absence of
      symptomatic medication could be a biomarker helping in the diagnosis of CM.

PMID- 23975873
TI  - Titin and centronuclear myopathy: The tip of the iceberg for TTN-ic mutations?

PMID- 23975874
TI  - Migraine and white matter hyperintensities: the ARIC MRI study.
AB  - OBJECTIVE: Migraine is associated with white matter hyperintensities (WMH) cross
      sectionally, but its effect on WMH progression is uncertain. METHODS:
      Participants in the Atherosclerosis Risk in Communities cohort study (n = 10,924)
      completed a standardized headache questionnaire between 1993 and 1995. A subset
      of participants (n = 1,028) received 2 MRIs 8 to 12 years apart: once at the time
      of headache ascertainment, and again from 2004 to 2006. WMH were quantified using
      both a visually graded score (0-9) and semiautomated volumetric analysis. Linear
      and logistic regression models adjusted for age, sex, and other vascular risk
      factors were constructed. RESULTS: Individuals who had migraine without aura were
      cross-sectionally associated with an 87% greater odds of having a WMH score >=3
      than individuals without headache (adjusted odds ratio = 1.87; 95% confidence
      interval [CI]: 1.04, 3.37). Participants with migraine had an average of 2.65
      cm(3) more WMH than those without headache (95% CI: 0.06, 5.24). However, there
      was no significant difference in WMH progression over the study period between
      individuals with and without migraine (1.58 cm(3) more progression for
      individuals with migraine compared to those without; 95% CI: -0.37, 3.53).
      CONCLUSION: Migraine is associated with WMH volume cross-sectionally but not with
      WMH progression over time. This suggests that the association between migraine
      and WMH is stable in older age and may be primarily attributable to changes
      occurring earlier in life, although further work is needed to confirm these
      findings.

PMID- 23975876
TI  - [HSV lymphadenitis in chronic lymphocytic leukemia -- a rare but difficult
      differential diagnosis].

PMID- 23975875
TI  - Recessive truncating titin gene, TTN, mutations presenting as centronuclear
      myopathy.
AB  - OBJECTIVE: To identify causative genes for centronuclear myopathies (CNM), a
      heterogeneous group of rare inherited muscle disorders that often present in
      infancy or early life with weakness and hypotonia, using next-generation
      sequencing of whole exomes and genomes. METHODS: Whole-exome or -genome
      sequencing was performed in a cohort of 29 unrelated patients with
      clinicopathologic diagnoses of CNM or related myopathy depleted for cases with
      mutations of MTM1, DNM2, and BIN1. Immunofluorescence analyses on muscle
      biopsies, splicing assays, and gel electrophoresis of patient muscle proteins
      were performed to determine the molecular consequences of mutations of interest.
      RESULTS: Autosomal recessive compound heterozygous truncating mutations of the
      titin gene, TTN, were identified in 5 individuals. Biochemical analyses
      demonstrated increased titin degradation and truncated titin proteins in patient
      muscles, establishing the impact of the mutations. CONCLUSIONS: Our study
      identifies truncating TTN mutations as a cause of congenital myopathy that is
      reported as CNM. Unlike the classic CNM genes that are all involved in excitation
      contraction coupling at the triad, TTN encodes the giant sarcomeric protein
      titin, which forms a myofibrillar backbone for the components of the contractile
      machinery. This study expands the phenotypic spectrum associated with TTN
      mutations and indicates that TTN mutation analysis should be considered in cases
      of possible CNM without mutations in the classic CNM genes.

PMID- 23975877
TI  - Radiofrequency ablation of osteoid osteomas: analgesia and patient satisfaction
      in long-term follow-up.
AB  - PURPOSE: To review the long term clinical outcomes in the treatment of osteoid
      osteoma (OO) using radiofrequency ablation (RFA). MATERIALS AND METHODS: Our
      retrospective study included 59 patients who were treated in the period from
      April 2001 to December 2012 due to a symptomatic OO using RFA. Here, the
      occurrence of complications and postoperative recurrence, as well as
      postoperative patient satisfaction were examined. Patients satisfaction was
      assessed by means of a telephone interview with the visual analogue scale (VAS).
      RESULTS: Mean follow-up was 50 months (2 - 116 months). The average size of the
      nidus was 6 mm (range 2 - 14 mm). After initial radiofrequency ablation 11.8 %
      (7/59) of patient showed a recurrence of symptoms. Symptoms could successfully be
      treated by a second ablation in 5 patients. Assisted success rate was therefore
      96.6 % (57/59). The complication rate was 5.1 % (2 major and one minor
      complication). Furthermore we report a very high patient satisfaction and
      acceptance of therapy. CONCLUSION: RFA is a very successful therapy of
      symptomatic OOs with a high patient satisfaction. KEY POINTS: ? Osteoid osteomas
      (OO) are rare benign bone tumors of the childhood and adolescence. ? Treatment of
      OOs with minimal-invasive radiofrequency ablation (RFA) shows a high patient
      satisfaction. ? RFA is by now the standard therapy of symptomatic OOs.

PMID- 23975879
TI  - Groin Pain in Athletes.

PMID- 23975878
TI  - Automated quantification of pulmonary perfused blood volume by dual-energy CTPA
      in chronic thromboembolic pulmonary hypertension.
AB  - OBJECTIVES: The aim of the study was to determine whether automated
      quantification of pulmonary perfused blood volume (PBV) in dual-energy computed
      tomography pulmonary angiography (DE-CTPA) can be used to assess the severity of
      chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Automated
      quantification of PBV was performed in 25 consecutive CTEPH patients undergoing
      DE-CTPA. PBV values were correlated with cardiac index and pulmonary vascular
      resistance quantified by right heart catheterization and walking distance in the
      6-minute walk test using Pearson's correlation coefficient and multivariate
      linear regression analysis to control for age and gender. RESULTS: DE-CTPA
      derived PBV values inversely correlated with systolic (r = -0.64, p = 0.001) and
      mean (r = -0.57, p = 0.004) pulmonary arterial pressure. There was a trend for
      PBV values to inversely correlate with pulmonary vascular resistance (r = -0.20,
      p = 0.35). No significant correlation was found between PBV values and cardiac
      index or 6-minute walking distance. These correlations were confirmed to be
      independent of age and gender on multivariate linear regression analysis.
      CONCLUSION: DE-CTPA can be used for an automated quantification of pulmonary PBV
      in chronic thromboembolic pulmonary hypertension. PBV values correlate inversely
      with systolic and mean pulmonary arterial pressure and can thus be used to
      estimate the severity of pulmonary hypertension in these patients. Citation
      Format: * Meinel FG, Graef A, Thierfelder KM et al. Automated Quantification of
      Pulmonary Perfused Blood Volume by Dual-Energy CTPA in Chronic Thromboembolic
      Pulmonary Hypertension. Fortschr Rontgenstr 2014; 186: 151 - 156.

PMID- 23975880
TI  - On the Relationship between Molecular Hit Rates in High-Throughput Screening and
      Molecular Descriptors.
AB  - High-throughput screening (HTS) is widely used in the pharmaceutical industry to
      identify novel chemical starting points for drug discovery projects. The current
      study focuses on the relationship between molecular hit rate in recent in-house
      HTS and four common molecular descriptors: lipophilicity (ClogP), size (heavy
      atom count, HEV), fraction of sp(3)-hybridized carbons (Fsp3), and fraction of
      molecular framework (f(MF)). The molecular hit rate is defined as the fraction of
      times the molecule has been assigned as active in the HTS campaigns where it has
      been screened. Beta-binomial statistical models were built to model the molecular
      hit rate as a function of these descriptors. The advantage of the beta-binomial
      statistical models is that the correlation between the descriptors is taken into
      account. Higher degree polynomial terms of the descriptors were also added into
      the beta-binomial statistic model to improve the model quality. The relative
      influence of different molecular descriptors on molecular hit rate has been
      estimated, taking into account that the descriptors are correlated to each other
      through applying beta-binomial statistical modeling. The results show that ClogP
      has the largest influence on the molecular hit rate, followed by Fsp3 and HEV.
      f(MF) has only a minor influence besides its correlation with the other molecular
      descriptors.

PMID- 23975881
TI  - Advancing the understanding of craving during smoking cessation attempts: a
      demonstration of the time-varying effect model.
AB  - INTRODUCTION: Advancing the understanding of smoking cessation requires a complex
      and nuanced understanding of behavior change. To this end, ecological momentary
      assessments (EMA) are now being collected extensively. The time-varying effect
      model (TVEM) is a statistical technique ideally suited to model processes that
      unfold as behavior and nicotine dependence change. Coefficients are expressed
      dynamically over time and are represented as smooth functions of time. METHODS:
      The TVEM approach is demonstrated using data from a smoking-cessation trial. Time
      varying effects of baseline nicotine dependence (a time-invariant covariate) and
      negative affect (a time-varying covariate) on urge to smoke during a quit attempt
      were estimated for monotherapy, combination therapy, and placebo groups. SAS
      syntax for conducting TVEM is provided so that readers can adapt it for their
      research. RESULTS: During the first 2 days after quitting, the association
      between negative affect and craving was significantly stronger among individuals
      in the placebo group, suggesting an early positive impact of treatment. For the
      monotherapy and combination therapy groups, during the second week of the quit
      attempt, baseline dependence was less strongly related to craving compared with
      the placebo group, indicating a different positive impact of treatments later in
      the quit attempt. CONCLUSIONS: The results reveal information about the
      underlying dynamics that unfold during a quit attempt and how monotherapy and
      combination therapy impact those processes. This suggests possible mechanisms to
      target in an intervention and indicates timepoints that hold the greatest promise
      for effective treatment. TVEM is a straightforward approach to examining time
      varying processes embedded in EMA.

PMID- 23975883
TI  - Allergic bronchopulmonary aspergillosis in garden waste (compost) collectors-
      occupational implications.
AB  - The separation of rotting garden material from general domestic waste and its
      collection for processing in industrial composting sites is a relatively new
      industry in the UK. Two cases of allergic bronchopulmonary aspergillosis and the
      results of health surveillance are described in a team of 28 garden waste
      (compost) collectors. A few cases of extrinsic allergic alveolitis due to
      Aspergillus fumigatus have previously been reported in compost workers. In the
      absence of any guidance from research and to prevent similar cases of a
      potentially serious illness, we advise that new starters to the job of collecting
      or processing compost are screened for asthma and aspergillus sensitivity, cystic
      fibrosis, bronchiectasis and immunodeficiency if their exposure to high levels of
      Aspergillus sp cannot be controlled. Annual health surveillance for these workers
      is also recommended. 

PMID- 23975884
TI  - Viral persistence in HIV infection: much known, much to learn.

PMID- 23975882
TI  - Mesenchymal stem cells as a vector for the inflammatory prostate
      microenvironment.
AB  - Mesenchymal stem cells (MSCs) have an inherent tropism for sites of inflammation,
      which are frequently present in sites of cancer, including prostatic lesions.
      MSCs have been defined as CD73/CD90/CD105 triple-positive cells in the absence of
      hematopoietic lineage markers with the ability to differentiate into multiple
      mesodermal lineages, including osteoblasts, adipocytes, and chondrocytes. Our
      group has previously demonstrated that MSCs represent between 0.01 and 1.1% of
      the total cells present in human prostatectomy tissue. In addition to their multi
      lineage differentiation potential, MSCs are immunoprivileged in nature and have a
      range of immunomodulatory effects on both the innate and adaptive arms of the
      immune system. MSCs have been detected in an increasing array of tissues, and
      evidence suggests that they are likely present in perivascular niches throughout
      the body. These observations suggest that MSCs represent critical mediators of
      the overall immune response during physiological homeostasis and likely
      contribute to pathophysiological conditions as well. Chronic inflammation has
      been suggested as an initiating event and progression factor in prostate
      carcinogenesis, a process in which the immunosuppressive properties of MSCs may
      play a role. MSCs have also been shown to influence malignant progression through
      a variety of other mechanisms, including effects on tumor proliferation,
      angiogenesis, survival, and metastasis. Additionally, human bone marrow-derived
      MSCs have been shown to traffic to human prostate cancer xenografts in
      immunocompromised murine hosts. The trafficking properties and immunoprivileged
      status of MSCs suggest that they can be exploited as an allogeneic cell-based
      vector to deliver cytotoxic or diagnostic agents for therapy.

PMID- 23975886
TI  - Accumulation of nitrate and nitrite in chilled leaves of rice seedlings is
      induced by high root temperature.
AB  - We previously found a novel type of chilling injury in the leaves of rice
      seedlings (Oryza sativa L. cv. Akitakomachi). The damage was only observed when
      the roots were not chilled (10  degrees C/25  degrees C, shoots/roots), but not
      when the whole seedling was chilled (10  degrees C/10  degrees C). In this
      report, we show that the chilling injury induced by high root temperature
      required nitrate and potassium together with a trace amount of iron, manganese or
      both in the nutrient solution during the treatment, and that the injury was
      increased by nitrogen starvation before chilling. Both nitrate and nitrite
      accumulated in the 10  degrees C/25  degrees C leaves when the nutrient solution
      contained nitrate. The nitrate accumulation in the 10  degrees C/25  degrees C
      leaves was highest at the end of the first light period, and was followed by a
      decrease with a concomitant increase in nitrite during the first dark period. The
      photosynthetic electron transport was completely lost in both PSII and PSI in the
      10  degrees C/25  degrees C leaves when the nutrient solution contained nitrate.
      However, the activities in the leaves of the 10  degrees C/25  degrees C plants
      treated with the nutrient solution lacking nitrate remained at approximately half
      those in the 10  degrees C/10 degrees C leaves. The photochemical quenching of
      Chl fluorescence and the P700 oxidation state were also intermediate between
      those in the 10  degrees C/25  degrees C and 10  degrees C/10 degrees C leaves of
      plants supplied with the complete nutrients. Thus, the chilling injury was
      closely linked to the accumulation of nitrate and nitrite, as well as to a
      malfunction of photosynthesis in the 10  degrees C/25  degrees C leaves.

PMID- 23975885
TI  - Increase in 2-long terminal repeat circles and decrease in D-dimer after
      raltegravir intensification in patients with treated HIV infection: a randomized,
      placebo-controlled trial.
AB  - BACKGROUND: The degree to which human immunodeficiency virus (HIV) continues to
      replicate during antiretroviral therapy (ART) is controversial. We conducted a
      randomized, double-blind, placebo-controlled study to assess whether raltegravir
      intensification reduces low-level viral replication, as defined by an increase in
      the level of 2-long terminal repeat (2-LTR) circles. METHODS: Thirty-one subjects
      with an ART-suppressed plasma HIV RNA level of <40 copies/mL and a CD4(+) T-cell
      count of >=350 cells/mm(3) for >=1 year were randomly assigned to receive
      raltegravir 400 mg twice daily or placebo for 24 weeks. 2-LTR circles were
      analyzed by droplet digital polymerase chain reaction at weeks 0, 1, 2, and 8.
      RESULTS: The median duration of ART suppression was 3.8 years. The raltegravir
      group had a significant increase in the level of 2-LTR circles, compared to the
      placebo group. The week 1 to 0 ratio was 8.8-fold higher (P = .0025) and the week
      2 to 0 ratio was 5.7-fold higher (P = .023) in the raltegravir vs. placebo group.
      Intensification also led to a statistically significant decrease in the D-dimer
      level, compared to placebo (P = .045). CONCLUSIONS: Raltegravir intensification
      resulted in a rapid increase in the level of 2-LTR circles in a proportion of
      subjects, indicating that low-level viral replication persists in some
      individuals even after long-term ART. Intensification also reduced the D-dimer
      level, a coagulation biomarker that is predictive of morbidity and mortality
      among patients receiving treatment for HIV infection.

PMID- 23975887
TI  - Evidence for a bacterial lipopolysaccharide-recognizing G-protein-coupled
      receptor in the bacterial engulfment by Entamoeba histolytica.
AB  - Entamoeba histolytica is the causative agent of amoebic dysentery, a worldwide
      protozoal disease that results in approximately 100,000 deaths annually. The
      virulence of E. histolytica may be due to interactions with the host bacterial
      flora, whereby trophozoites engulf colonic bacteria as a nutrient source. The
      engulfment process depends on trophozoite recognition of bacterial epitopes that
      activate phagocytosis pathways. E. histolytica GPCR-1 (EhGPCR-1) was previously
      recognized as a putative G-protein-coupled receptor (GPCR) used by Entamoeba
      histolytica during phagocytosis. In the present study, we attempted to
      characterize EhGPCR-1 by using heterologous GPCR expression in Saccharomyces
      cerevisiae. We discovered that bacterial lipopolysaccharide (LPS) is an activator
      of EhGPCR-1 and that LPS stimulates EhGPCR-1 in a concentration-dependent manner.
      Additionally, we demonstrated that Entamoeba histolytica prefers to engulf
      bacteria with intact LPS and that this engulfment process is sensitive to
      suramin, which prevents the interactions of GPCRs and G-proteins. Thus, EhGPCR-1
      is an LPS-recognizing GPCR that is a potential drug target for treatment of
      amoebiasis, especially considering the well-established drug targeting to GPCRs. 

PMID- 23975888
TI  - bZIP transcription factors in the oomycete phytophthora infestans with novel DNA
      binding domains are involved in defense against oxidative stress.
AB  - Transcription factors of the basic leucine zipper (bZIP) family control
      development and stress responses in eukaryotes. To date, only one bZIP has been
      described in any oomycete; oomycetes are members of the stramenopile kingdom. In
      this study, we describe the identification of 38 bZIPs from the Phytophthora
      infestans genome. Half contain novel substitutions in the DNA-binding domain at a
      site that in other eukaryotes is reported to always be Asn. Interspecific
      comparisons indicated that the novel substitutions (usually Cys, but also Val and
      Tyr) arose after oomycetes diverged from other stramenopiles. About two-thirds of
      P. infestans bZIPs show dynamic changes in mRNA levels during the life cycle,
      with many of the genes being upregulated in sporangia, zoospores, or germinated
      zoospore cysts. One bZIP with the novel Cys substitution was shown to reside in
      the nucleus throughout growth and development. Using stable gene silencing, the
      functions of eight bZIPs with the Cys substitution were tested. All but one were
      found to play roles in protecting P. infestans from hydrogen peroxide-induced
      injury, and it is proposed that the novel Cys substitution serves as a redox
      sensor. A ninth bZIP lacking the novel Asn-to-Cys substitution, but having Cys
      nearby, was also shown through silencing to contribute to defense against
      peroxide. Little effect on asexual development, plant pathogenesis, or resistance
      to osmotic stress was observed in transformants silenced for any of the nine
      bZIPs. 

PMID- 23975890
TI  - Health behaviors of cancer survivors: the Fourth Korea National Health and
      Nutrition Examination Survey (KNHANES IV, 2007-09).
AB  - OBJECTIVE: This study aimed to describe the health behaviors of cancer survivors
      in the Republic of Korea and to compare them with the health behaviors of two
      control groups: (i) individuals with no history of cancer but with other chronic
      diseases and (ii) individuals with no history of cancer or other chronic
      diseases. METHODS: This is a cross-sectional study of 17 311 adults at least 19
      years of age who participated in the Fourth Korea National Health and Nutrition
      Examination Survey (2007-09). Smoking, alcohol drinking, physical activity and
      cancer screening behaviors of cancer survivors were assessed and compared with
      those of the two control groups. chi(2) tests and multiple logistic regression
      analyses were performed to determine the likelihood and predictors of health
      behaviors. RESULTS: The proportion of cancer survivors who were current smokers,
      heavy drinkers and engaged in physical activity were 9.6, 6.6 and 26.0%,
      respectively. Cancer screening rates reported among survivors were 44.2, 17.0,
      49.8 and 47.7% for stomach, colorectal, breast and cervical cancers,
      respectively. Cancer survivors showed lower smoking and alcohol drinking rates
      compared with both control groups after adjusting for sex, age, marital status,
      education, household income and health insurance. Cancer survivors also showed
      stomach, breast and cervical cancer screening rates that differed from both
      control groups. However, in multiple analyses, these differences were not
      significant. CONCLUSIONS: Cancer survivors are more likely to adopt good health
      behaviors than individuals without a history of cancer. Further study is needed
      to determine the factors that lead to continued unhealthy behaviors after cancer
      diagnosis.

PMID- 23975889
TI  - Nitrogen source-dependent capsule induction in human-pathogenic cryptococcus
      species.
AB  - Cryptococcus neoformans and C. gattii cause meningoencephalitis and are an
      increasing human health threat. These pathogenic Cryptococcus species are
      neurotropic and persist in the cerebrospinal fluid (CSF) of the mammalian host
      during infection. In order to survive in the host, pathogenic fungi must procure
      nutrients, such as carbon and nitrogen, from the CSF. To enhance our
      understanding of nutrient acquisition during central nervous system infection by
      Cryptococcus species, we examined the utilization of nitrogen sources available
      in CSF. We screened for the growth and capsule production of 817 global
      environmental and clinical isolates on various sources of nitrogen. Both
      environmental and clinical strains grew robustly on uric acid, Casamino Acids,
      creatinine, and asparagine as sole nitrogen sources. Urea induced the greatest
      magnitude of capsule induction. This induction was greater in Cryptococcus gattii
      than in C. neoformans. We confirmed the ability of nonpreferred nitrogen sources
      to increase capsule production in pathogenic species of Cryptococcus. Since urea
      is metabolized to ammonia and CO(2) (a known signal for capsule induction), we
      examined urea metabolism mutants for their transcriptional response to urea
      regarding capsule production. The transcriptional profile of C. neoformans under
      urea-supplemented conditions revealed both similar and unique responses to other
      capsule-inducing conditions, including both intra- and extracellular urea
      utilization. As one of the most abundant nitrogen sources in the CSF, the ability
      of Cryptococcus to import urea and induce capsule production may substantially
      aid this yeast's survival and propagation in the host.

PMID- 23975891
TI  - Characterization of four nuclear-encoded plastid RNA polymerase sigma factor
      genes in the liverwort Marchantia polymorpha: blue-light- and multiple stress
      responsive SIG5 was acquired early in the emergence of terrestrial plants.
AB  - The plastids of plant cells each contain their own genome, and a bacterial-type
      RNA polymerase called plastid-encoded plastid RNA polymerase (PEP) is involved in
      transcription of this genome. While the catalytic core subunits are encoded by
      the plastid genome, the specificity subunit of PEP, sigma, is generally encoded
      by the nuclear genome and imported into plastids from the cytoplasm after
      translation. In this study, we identified and analyzed four sigma factor genes
      from the nuclear genome of a liverwort, Marchantia polymorpha. Phylogenetic
      analysis suggested that three of the four genes were orthologous to vascular
      plant genes and thus they were named MpSIG1, MpSIG2 and MpSIG5. The remaining
      gene was named MpSIGX. The gene products were predicted to localize to the
      plastid, and this prediction was experimentally demonstrated by expressing yellow
      fluorescent protein fusion genes in vivo. As with SIG5 genes of other plant
      species, expression of MpSIG5 was induced by blue-light irradiation and also
      under various stress conditions, indicating that the regulatory mechanism
      responsible is conserved among divergent plant species. However, while the major
      role of SIG5 in vascular plants is to repair the damaged PSII reaction center
      through psbD gene transcription, the relevant blue-light-responsive promoter
      (psbD-BLRP) was not found in M. polymorpha and psbD transcript accumulation did
      not occur in conjunction with MpSIG5 induction. Thus, the physiological role of
      SIG5 is probably divergent among plant phyla. 

PMID- 23975892
TI  - CXCL6 antibody neutralization prevents lung inflammation and fibrosis in mice in
      the bleomycin model.
AB  - IPF is a chronic, progressive pulmonary disease, leading to respiratory failure.
      In search of mechanisms of IPF, we used the bleomycin-induced lung-injury model
      in mice, which causes acute inflammation that may progress to chronic lung
      inflammation and fibrosis. Here, we asked whether CXCL6/GCP-2, a member of the
      CXC chemokine superfamily, may be involved in IPF development. First, we reported
      an increase of CXCL6 levels in BALF from patients with IPF, as well as in the
      lung of mice, 24 h after bleomycin administration. To investigate whether CXCL6
      played a role in experimental bleomycin-induced pulmonary fibrosis, we treated
      mice with an anti-mCXCL6 mAb that has been shown to inhibit neutrophil chemotaxis
      in vitro. CXCL6 antibody blockade attenuated acute inflammation with a reduced
      pulmonary neutrophil influx, IL-1beta, CXCL1, and TIMP-1 production. In the later
      phase (14 days after bleomycin exposure), lymphocyte recruitment and fibrosis
      markers, such as collagen and TIMP-1, were diminished, as well as collagen
      deposition and fibrotic lesion the lung. Therefore, the data suggest that CXCL6
      contributes to experimental pulmonary fibrosis, and CXCL6 inhibition might be
      used to reduce lung toxicity associated with bleomycin treatment. 

PMID- 23975893
TI  - Determinants of health care-seeking delay among tuberculosis patients in Shandong
      Province, China.
AB  - BACKGROUND: It is beneficial for tuberculosis patients to seek health care in
      time. The aim of this study was to understand the situation of initial health
      care-seeking delay among tuberculosis patients in eastern China, and explore its
      influencing factors, to provide a basis for formulating related polices and
      reducing its transmission. METHODS: A cross-sectional survey was conducted in six
      counties of Shandong Province, China, and we selected study sites by multi-stage
      random sampling. Subjects were pulmonary tuberculosis patients registered with
      the county tuberculosis dispensaries at study sites that completed treatment
      during the period October 2006 to September 30, 2007. RESULTS: For the 819 cases
      of pulmonary tuberculosis, the median initial health care-seeking delay time was
      6 days, and 49.8% of them were initial health care-seeking delayed. The logistic
      regression analysis showed that marriage (odds ratio = 0.354, 95% confidence
      interval: 0.193-0.650) and knowledge of the national tuberculosis subsidy policy
      (odds ratio = 1.753, 95% confidence interval: 1.258-2.441) were associated with
      initial health care-seeking delay. CONCLUSION: Changing the perception of
      patients and popularizing the national tuberculosis subsidy policy will do well
      towards reducing initial health care-seeking delay.

PMID- 23975894
TI  - At what age is hydrocephalus detected, and what is the role of head circumference
      measurements?
AB  - To investigate at what age hydrocephalus is detected and to assess the role of
      head circumference measurements in detecting hydrocephalus, we performed a
      retrospective chart review in children with hydrocephalus treated in a tertiary
      paediatric hospital in the Netherlands. The study group contained 146 patients;
      38 patients (31%) were referred because of abnormalities in head circumference.
      Eighty-nine per cent of the patients were detected in the first year of life.
      After this period, no patients were referred because of an abnormal head
      circumference. Therefore, head circumference measurements seem to have little
      value for detecting hydrocephalus after the first year of life. 

PMID- 23975895
TI  - Health effects of the crisis: challenges for science and policy.

PMID- 23975896
TI  - In celebration of the 100th anniversary of the lipid hypothesis of
      atherosclerosis.
AB  - This year marks the 100th anniversary of the publication of Anitschkow's classic
      paper proposing the central role of hypercholesterolemia in atherogenesis. We at
      the Journal of Lipid Research take this occasion to acknowledge the debt we all
      owe to Anitschkow and his colleagues for getting us on the right track. As
      discussed below in detail, his contributions were insightful and went well beyond
      simply pinpointing hypercholesterolemia as a major etiologic factor. Anitschkow's
      work led him to define most of the key elements in the initiation and evolution
      of lesions in animal models of atherogenesis. 

PMID- 23975897
TI  - Identification and dynamics of Arabidopsis adaptor protein-2 complex and its
      involvement in floral organ development.
AB  - The adaptor protein-2 (AP-2) complex is a heterotetramer involved in clathrin
      mediated endocytosis of cargo proteins from the plasma membrane in animal cells.
      The homologous genes of AP-2 subunits are present in the genomes of plants;
      however, their identities and roles in endocytic pathways are not clearly defined
      in plants. Here, we reveal the molecular composition of the AP-2 complex of
      Arabidopsis thaliana and its dynamics on the plasma membrane. We identified all
      of the alpha-, beta-, sigma-, and MU-subunits of the AP-2 complex and detected a
      weak interaction of the AP-2 complex with clathrin heavy chain. The MU-subunit
      protein fused to green fluorescent protein (AP2M-GFP) was localized to the plasma
      membrane and to the cytoplasm. Live-cell imaging using a variable-angle
      epifluorescence microscope revealed that AP2M-GFP transiently forms punctate
      structures on the plasma membrane. Homozygous ap2m mutant plants exhibited
      abnormal floral structures, including reduced stamen elongation and delayed
      anther dehiscence, which led to a failure of pollination and a subsequent
      reduction of fertility. Our study provides a molecular basis for understanding AP
      2-dependent endocytic pathways in plants and their roles in floral organ
      development and plant reproduction. 

PMID- 23975898
TI  - Adaptor protein complex 2-mediated endocytosis is crucial for male reproductive
      organ development in Arabidopsis.
AB  - Fertilization in flowering plants requires the temporal and spatial coordination
      of many developmental processes, including pollen production, anther dehiscence,
      ovule production, and pollen tube elongation. However, it remains elusive as to
      how this coordination occurs during reproduction. Here, we present evidence that
      endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a
      crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays
      multiple defects in pollen production and viability, as well as elongation of
      staminal filaments and pollen tubes, all of which are pivotal processes needed
      for fertilization. Of these abnormalities, the defects in elongation of staminal
      filaments and pollen tubes were partially rescued by exogenous auxin. Moreover,
      DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in
      filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants
      displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4-(4
      diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an
      endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2
      (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by
      treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these
      results, we propose that AP-2-dependent endocytosis plays a crucial role in
      coordinating the multiple developmental aspects of male reproductive organs by
      modulating cellular auxin level through the regulation of the amount and polarity
      of PINs. 

PMID- 23975901
TI  - Effect of voluntary hyperventilation with supplemental CO2 on pulmonary O2 uptake
      and leg blood flow kinetics during moderate-intensity exercise.
AB  - Pulmonary O2 uptake (V(O2p)) and leg blood flow (LBF) kinetics were examined at
      the onset of moderate-intensity exercise, during hyperventilation with and
      without associated hypocapnic alkalosis. Seven male subjects (25 +/- 6 years old;
      mean +/- SD) performed alternate-leg knee-extension exercise from baseline to
      moderate-intensity exercise (80% of estimated lactate threshold) and completed
      four to six repetitions for each of the following three conditions: (i) control
      [CON; end-tidal partial pressure of CO2 (P(ET, CO2)) ~40 mmHg], i.e. normal
      breathing with normal inspired CO2 (0.03%); (ii) hypocapnia (HYPO; P(ET, CO2) ~20
      mmHg), i.e. sustained hyperventilation with normal inspired CO2 (0.03%); and
      (iii) normocapnia (NORMO; P(ET, CO2) ~40 mmHg), i.e. sustained hyperventilation
      with elevated inspired CO2 (~5%). The V(O2p) was measured breath by breath using
      mass spectrometry and a volume turbine. Femoral artery mean blood velocity was
      measured by Doppler ultrasound, and LBF was calculated from femoral artery
      diameter and mean blood velocity. Phase 2 V(O2p) kinetics (tauV(O2p)) was
      different (P < 0.05) amongst all three conditions (CON, 19 +/- 7 s; HYPO, 43 +/-
      17 s; and NORMO, 30 +/- 8 s), while LBF kinetics (tauLBF) was slower (P < 0.05)
      in HYPO (31 +/- 9 s) compared with both CON (19 +/- 3 s) and NORMO (20 +/- 6 s).
      Similar to previous findings, HYPO was associated with slower V(O2p) and LBF
      kinetics compared with CON. In the present study, preventing the fall in end
      tidal P(CO2) (NORMO) restored LBF kinetics, but not V(O2p) kinetics, which
      remained 'slowed' relative to CON. These data suggest that the hyperventilation
      manoeuvre itself (i.e. independent of induced hypocapnic alkalosis) may
      contribute to the slower V(O2p) kinetics observed during HYPO.

PMID- 23975900
TI  - Mutagenesis of individual pentatricopeptide repeat motifs affects RNA binding
      activity and reveals functional partitioning of Arabidopsis PROTON gradient
      regulation3.
AB  - Pentatricopeptide repeat (PPR) proteins bind RNA and act in multiple eukaryotic
      processes, including RNA editing, RNA stability, and translation. Here, we
      investigated the mechanism underlying the functional versatility of Arabidopsis
      thaliana proton gradient regulation3 (PGR3), a chloroplast protein harboring 27
      PPR motifs. Previous studies suggested that PGR3 acts in (1) stabilization of
      photosynthetic electron transport L (petL) operon RNA, (2) translation of petL,
      and (3) translation of ndhA. We showed here that replacement of the 4th amino
      acid of the 12th PPR with nonpolar or charged amino acids abolished functions (1)
      and (2) but not (3) of PGR3 by compromising the function of this specific PPR.
      This discovery enabled us to knock out the RNA binding ability of individual PPR
      motifs. Consequently, we showed that the 16 N-terminal PPRs were sufficient for
      function (1) via sequence-specific RNA binding, whereas the 11 C-terminal motifs
      were essential for functions (2) and (3) by activating translation. We also
      clarified that the 14th amino acid of the 12th PPR should be positively charged
      to make the PPR functionally active. Our finding opens up the possibility of
      selectively manipulating the functions of PPR proteins.

PMID- 23975899
TI  - The clathrin adaptor complex AP-2 mediates endocytosis of brassinosteroid
      insensitive1 in Arabidopsis.
AB  - Clathrin-mediated endocytosis (CME) regulates many aspects of plant development,
      including hormone signaling and responses to environmental stresses. Despite the
      importance of this process, the machinery that regulates CME in plants is largely
      unknown. In mammals, the heterotetrameric adaptor protein complex-2 (AP-2) is
      required for the formation of clathrin-coated vesicles at the plasma membrane
      (PM). Although the existence of AP-2 has been predicted in Arabidopsis thaliana,
      the biochemistry and functionality of the complex is still uncharacterized. Here,
      we identified all the subunits of the Arabidopsis AP-2 by tandem affinity
      purification and found that one of the large AP-2 subunits, AP2A1, localized at
      the PM and interacted with clathrin. Furthermore, endocytosis of the leucine-rich
      repeat receptor kinase, brassinosteroid insensitive1 (BRI1), was shown to depend
      on AP-2. Knockdown of the two Arabidopsis AP2A genes or overexpression of a
      dominant-negative version of the medium AP-2 subunit, AP2M, impaired BRI1
      endocytosis and enhanced the brassinosteroid signaling. Our data reveal that the
      CME machinery in Arabidopsis is evolutionarily conserved and that AP-2 functions
      in receptor-mediated endocytosis.

PMID- 23975902
TI  - Non-quantal release of acetylcholine in rat atrial myocardium is inhibited by
      noradrenaline.
AB  - In the mammalian myocardium, ACh, which is the main neurotransmitter of cardiac
      parasympathetic postganglionic fibres, can be released via both quantal
      (vesicular) and non-quantal (non-vesicular) mechanisms of secretion. Non-quantal
      release is continuous and independent of vagus activity and exocytosis of ACh
      containing vesicles. During the incubation of myocardium in the presence of
      acetylcholinesterase (AChE) inhibitors, non-quantal ACh release leads to
      accumulation of ACh in the myocardium and cholinergic effects, which are
      proportional to the intensity of non-quantal secretion. The aim of the present
      study was to reveal whether non-quantal release of ACh can be modulated by
      another major cardioregulator, noradrenaline, or whether it represents
      uncontrolled leakage of ACh from cholinergic fibres. Cholinergic changes of
      electrical activity induced by the AChE inhibitor paraoxon (5 * 10(-6) M) in
      isolated rat right atrial preparations were determined by means of a standard
      microlectrode technique and used as a measure of the intensity of non-quantal
      release. Noradrenaline (10(-7) and 10(-6) M) substantially suppressed, but did
      not abolish, effects of paraoxon via stimulation of alpha-adrenoceptors, because
      all experiments were conducted in the presence of the beta-blocker propranolol (5
      * 10(-6) M). A blocker of ganglionic transmission, hexamethonium bromide (10(-4)
      M), failed to alter the inhibitory effect of noradrenaline, indicating that only
      non-quantal ACh release is suppressed by this neurotransmitter. The effects of
      noradrenaline could be reduced by the alpha2-antagonist yohimbine (10(-6) M).
      However, both the alpha1-agonist phenylephrine (10(-6) M) and the alpha2-agonist
      clonidine (10(-6) M) significantly inhibited the cholinergic effects of paraoxon,
      indicating the possible involvement of both alpha-adrenoceptor subtypes in
      mediation of the adrenergic inhibition of non-quantal ACh release. Thus, cardiac
      non-quantal ACh release can be negatively regulated by noradrenaline, providing
      another facet of sympathetic-parasympathetic interaction in the heart.

PMID- 23975903
TI  - Enhanced purinergic contractile responses and P2X1 receptor expression in
      detrusor muscle during cycles of hypoxia-glucopenia and reoxygenation.
AB  - Bladders from patients with detrusor overactivity have an increased atropine
      resistant contractile response to nerve stimulation. The bladder has also been
      shown to be very susceptible to hypoxia-glucopenia and reperfusion injury,
      leading to the hypothesis that episodes of hypoxia-glucopenia and reoxygenation
      result in increased atropine-resistant responses to nerve stimulation in the
      detrusor muscle. Detrusor muscle strips were suspended in a Perspex organ bath
      chamber of volume 0.2 ml perfused with Krebs solution at 37 degrees C aerated
      with 21% O2, 5% CO2 and the balance nitrogen. Hypoxia-glucopenia was induced by
      switching perfusion to Krebs solution without glucose, gassed with 95% nitrogen
      and 5% CO2. Atropine-resistant contractile responses increased by 40.5 +/- 7.3%
      after four cycles of hypoxia-glucopenia (10 min) and reoxygenation (1 h), whereas
      alpha,beta-methylene ATP-resistant responses did not increase. Expression of P2X1
      receptors in the bladder was increased after hypoxia-glucopenia and reoxygenation
      cycling, and ATP release from stimulated bladder strips during cycling was also
      increased. Other P2X receptor-mediated mechanisms may also be involved in the
      augmentation of bladder contraction during hypoxia-glucopenia and reoxygenation
      cycling, because a non-specific P2X antagonist blocked most of the augmented
      response, whereas a P2X1-specific antagonist prevented only part of the
      augmentation of contractile response induced by hypoxia-glucopenia and
      reoxygenation. In conclusion, four cycles of hypoxia-glucopenia and reoxygenation
      increased the purinergic, but not the cholinergic, contractile responses to nerve
      stimulation. Increased P2X1 receptor expression and ATP release may have
      contributed to the augmentation of contractile response induced by hypoxia
      glucopenia and reoxygenation. Purinergic antagonists may, therefore, be a useful
      therapeutic option for the treatment of overactive bladder with increased
      purinergic-mediated contractions.

PMID- 23975904
TI  - A cause without an effect? Primary prevention and causation.
AB  - Clinical primary prevention eliminates or preempts either a susceptibility or
      risk (synergistically a cause) in order to avoid a specific harm.
      Philosophically, primary prevention gets caught in the metaphysical controversy
      of the "hard questions" of whether it is possible to "cause not" both through a
      positive action (preventive act causes no harm) or no action (avoiding something
      causes no harm). I examine my previously proposed four-step definition of the
      process of prevention, discuss its limitations in light of the "hard questions,"
      and then offer a revised five-step process definition that eliminates the "cause
      not" concerns by changing the goal of prevention from avoiding harm, a negative
      state, to achieving optimal health, a positive state. 

PMID- 23975905
TI  - The role of emotions in clinical reasoning and decision making.
AB  - What role, if any, should emotions play in clinical reasoning and decision
      making? Traditionally, emotions have been excluded from clinical reasoning and
      decision making, but with recent advances in cognitive neuropsychology they are
      now considered an important component of them. Today, cognition is thought to be
      a set of complex processes relying on multiple types of intelligences. The role
      of mathematical logic (hypothetico-deductive thinking) or verbal linguistic
      intelligence in cognition, for example, is well documented and accepted; however,
      the role of emotional intelligence has received less attention-especially because
      its nature and function are not well understood. In this paper, I argue for the
      inclusion of emotions in clinical reasoning and decision making. To that end,
      developments in contemporary cognitive neuropsychology are initially examined and
      analyzed, followed by a review of the medical literature discussing the role of
      emotions in clinical practice. Next, a published clinical case is reconstructed
      and used to illustrate the recognition and regulation of emotions played during a
      series of clinical consultations, which resulted in a positive medical outcome.
      The paper's main thesis is that emotions, particularly in terms of emotional
      intelligence as a practical form of intelligence, afford clinical practitioners a
      robust cognitive resource for providing quality medical care. 

PMID- 23975906
TI  - In vivo quantification of calcitonin gene-related peptide receptor occupancy by
      telcagepant in rhesus monkey and human brain using the positron emission
      tomography tracer [11C]MK-4232.
AB  - Calcitonin gene-related peptide (CGRP) is a potent neuropeptide whose agonist
      interaction with the CGRP receptor (CGRP-R) in the periphery promotes
      vasodilation, neurogenic inflammation and trigeminovascular sensory activation.
      This process is implicated in the cause of migraine headaches, and CGRP-R
      antagonists in clinical development have proven effective in treating migraine
      related pain in humans. CGRP-R is expressed on blood vessel smooth muscle and
      sensory trigeminal neurons and fibers in the periphery as well as in the central
      nervous system. However, it is not clear what role the inhibition of central CGRP
      R plays in migraine pain relief. To this end, the CGRP-R positron emission
      tomography (PET) tracer [(11)C]MK-4232 (2-[(8R)-8-(3,5-difluorophenyl)-6,8-[6
      (11)C]dimethyl-10-oxo-6,9-diazaspiro[4.5]decan-9-yl]-N-[(2R)-2'-oxospiro[1,3
      dihydroindene-2,3'-1H-pyrrolo[2,3-b]pyridine]-5-yl]acetamide) was discovered and
      developed for use in clinical PET studies. In rhesus monkeys and humans,
      [(11)C]MK-4232 displayed rapid brain uptake and a regional brain distribution
      consistent with the known distribution of CGRP-R. Monkey PET studies with
      [(11)C]MK-4232 after intravenous dosing with CGRP-R antagonists validated the
      ability of [(11)C]MK-4232 to detect changes in CGRP-R occupancy in proportion to
      drug plasma concentration. Application of [(11)C]MK-4232 in human PET studies
      revealed that telcagepant achieved only low receptor occupancy at an efficacious
      dose (140 mg PO). Therefore, it is unlikely that antagonism of central CGRP-R is
      required for migraine efficacy. However, it is not known whether high central
      CGRP-R antagonism may provide additional therapeutic benefit. 

PMID- 23975907
TI  - Vasculitis of the gallbladder in early rheumatoid arthritis.
AB  - Vasculitis secondary to rheumatoid arthritis (RA) usually occurs in patients with
      high circulating titres of rheumatoid factor and established, chronic disease.
      Vasculitis of the gallbladder causing acute cholecystitis is an extremely rare
      manifestation of rheumatoid vasculitis. To our knowledge, this is the first case
      in which vasculitis occurred early in the course of disease. We report the case
      of a localised gallbladder vasculitis in a 74-year-old, newly diagnosed male
      patient with RA. He presented with acute abdominal pain, a history of
      constitutional symptoms and a 1-week history of polyarthritis of his wrist and
      hands. Cholecystitis was diagnosed clinically and radiologically and he underwent
      a laparoscopic cholecystectomy. Histopathology of the gallbladder confirmed
      cholecystitis and gallstones but in addition found small vessel vasculitis and
      rheumatoid nodules. This case illustrates that rheumatoid vasculitis can occur
      early in the onset of RA. Additionally, although rare, the gallbladder can be a
      site of localised rheumatoid vasculitis.

PMID- 23975908
TI  - Candida dubliniensis encrustation of an obstructing upper renal tract calculus.
AB  - We present the case of a 53-year-old man, with a history of alcohol abuse,
      requiring intensive care unit admission, with an obstructing right upper renal
      calculus and Klebsiella pneumoniae urosepsis. Ureteroscopic treatment of this
      obstruction displayed a small calculus within the renal pelvis completely
      encapsulated within a fungal bezoar. Laboratory analysis of the fungal mass found
      it to be Candida dubliniensis.

PMID- 23975909
TI  - Neonatal meningitis associated with osteomyelitis and epidural empyema.
AB  - Neonatal meningitis is a serious disease with significant mortality and
      morbidity. Its signs and symptoms are subtle, non-specific, atypical or absent.
      Cephalohaematoma is frequent in newborns and complications are uncommon,
      including local infection after haematogenous spread in the setting of
      bacteraemia or meningitis with a possibility of osteomyelitis, epidural abscess
      and subdural empyema. We report the case of a late preterm newborn, with an
      unremarkable pregnancy, born by vacuum-assisted vaginal delivery that presented
      in the fifth day of life with irritability, fever and grunting. Cerebrospinal
      fluid and blood cultures were positive for Escherichia coli. The patient had
      neurological deterioration despite adequate antibiotic therapy and brain MRI
      showed a right parietal epidural empyema, subcutaneous abscess, osteomyelitis and
      supratentorial hydrocephalus. The culture of the cephalohaematoma's abscess
      material was positive for E coli. Antibiotic therapy was continued for 8 weeks.
      The child, now 2 years old, has spastic tetraparesis with global development
      delay.

PMID- 23975910
TI  - Correction of class II division I malocclusion after extraction using Roth
      prescription.
AB  - A 19-year-old female patient with convex profile, posterior divergence having
      Angle's class II division 1 malocclusion with incompetent lips and rotations in
      various teeth was treated with fixed mechanotherapy. All the first premolars were
      extracted. Roth prescription of 0.022" * 0.028" slot was used. Proximal stripping
      was performed to correct a black triangle in the embrasure area in the upper
      anteriors. The entire treatment took about 15 months.

PMID- 23975911
TI  - Unilateral adrenal infarction in pregnancy.
AB  - A 25-year-old pregnant woman at 28 weeks gestational age presented with
      increasing abdominal pain and was found to have a unilateral adrenal infarction
      on a CT scan of the abdomen. Her medical history was unremarkable. There was no
      evidence of adrenal insufficiency with normal cortisol and adenocorticotropic
      hormone levels for pregnancy. Evaluation of thrombophilia disorders established
      the patient to be heterozygous for methylenetetrahydrofolatereductase C677T gene
      mutation as the only finding. The patient was anticoagulated to prevent
      contralateral thrombosis. At 32 weeks she experienced spontaneous rupture of
      membranes. One week later she delivered vaginally and remained anticoagulated for
      the puerperium.

PMID- 23975912
TI  - Posterior reversible encephalopathy syndrome revealing renal artery stenosis in a
      child.
AB  - A 14-year-old girl was admitted to the emergency department for repeated seizures
      with no fever. High blood pressure at admission was ascribed to the status
      epilepticus. Seizure recurrence promoted transfer to the paediatric intensive
      care unit. The MRI visualised bilateral, subcortical, white-matter lesions in the
      parietal and occipital lobes suggesting posterior reversible encephalopathy
      syndrome (PRES). Continuous nicardipine infusion corrected the hypertension and
      neurological manifestations within a few hours. The diagnostic workup showed
      right renal artery stenosis. Blood pressure returned to normal values for age
      after right nephrectomy. She was discharged home without treatment. She had no
      residual neurological impairments. This case highlights the risk of
      misinterpreting sustained hypertension in children with repeated seizures. We
      briefly review paediatric PRES, which is rare as compared to adults. Increased
      awareness among critical care physicians, together with greater availability of
      cerebral MRI, is decreasing the time to diagnosis.

PMID- 23975913
TI  - Panton-Valentine leukocidin-positive staphylococcus aureus necrotising pneumonia
      complicating pandemic A(H1N1) influenza infection.

PMID- 23975914
TI  - Indirect laminate veneer: a conservative novel approach.
AB  - Various treatment options and materials are available for restoration of an
      endodontically treated tooth. Laminate veneer is conservative treatment usually
      employed for aesthetic correction or improvement. The indirect composite is
      available in a wide range of shades and specific characterisation is easily
      performed chair side in the operatory area, which makes it a quick procedure and
      time saving for both the patient and the dentist. The physical properties and
      optical properties are good enough to use it as indirect restorative material, so
      in this particular case it was the material of choice for fabrication of laminate
      veneer on anterior tooth. In this case, the endodontically treated tooth with a
      fractured incisal edge was restored with indirect composite material.

PMID- 23975915
TI  - Atypical abdominal pain: post-traumatic transverse colon stricture.
AB  - A driver presented to the emergency department 1 day after an accident driving
      his excavator with abdominal pain and vomiting. He was admitted to the surgical
      ward 2 days later, after reattending. A CT scan revealed wall thickening and
      oedema in the transverse colon. This was supported by a subsequent CT virtual
      colonoscopy which raised the suspicion of neoplasia. A follow-up colonoscopy was
      not carried further than the transverse colon due to an indurated, tight
      stricture. Biopsies from that area showed ulceration and inflammatory changes non
      specific for ischaemia, drug-induced changes or inflammatory bowel disease. As a
      consequence of the subocclusive symptoms and the possibility of a neoplastic
      diagnosis, a laparoscopic-assisted transverse colectomy was performed. The
      histology of the resected segment revealed post-traumatic inflammation and
      fibrosis with no evidence of neoplasia.

PMID- 23975916
TI  - A fatal case of pure metaphyseal chondroblastoma.
AB  - The chondroblastoma (CB) is a rare cartilaginous tumour; it represents less than
      1% of all bone tumours. It is mostly localised at the level of the epiphysis of
      long bones. We report a fatal case of pure metaphyseal CB of the tibia in a 9
      year-old boy whose pulmonary metastases developed soon after operative therapy of
      the primary tumour.

PMID- 23975917
TI  - Aesthetic finger prosthesis with silicone biomaterial.
AB  - The fabrication of finger prosthesis is as much an art as it is science. The
      ideally constructed prosthesis must duplicate the missing structures so precisely
      that patients can appear in public without fear of attracting unwanted
      attraction. A 65-years-old patient reported with loss of his right index finger
      up to the second phalanx and wanted to get it replaced. An impression of the
      amputated finger and donor were made. A wax pattern of the prosthesis was
      fabricated using the donor impression; a trial was performed and flasked. Medical
      grade silicone was intrinsically stained to match the skin tone, following which
      it was packed, processed and finished. This clinical report describes a method of
      attaining retention by selective scoring of the master cast of partially
      amputated finger to enhance the vacuum effect at par with the proportional
      distribution of the positive forces on the tissues exerted by the prosthesis.

PMID- 23975918
TI  - Dyspnoea caused by a Chilaiditi syndrome: contribution of the non-invasive
      ventilation.

PMID- 23975919
TI  - Congenital pseudarthrosis of the clavicle causing thoracic outlet syndrome.
AB  - A 7-year-old girl presented with an asymptomatic right supraclavicular swelling.
      Radiographs were interpreted as showing a non-union of her clavicle. No treatment
      was given at this time. However, she represented 12 years later with right upper
      limb pain and altered sensation. Examination revealed a positive Allen's test on
      the right. Repeat radiographs demonstrated a pseudarthrosis of the clavicle,
      associated with a secondary complication of thoracic outlet syndrome with
      vascular and neurological complications present. Non-operative management failed
      to relieve her symptoms. Operative intervention successfully treated her
      symptoms.

PMID- 23975920
TI  - Spontaneous intestinal haematoma associated with neurofibromatosis type-1.
AB  - Vasculopathy in patients with neurofibromatosis-1 are rare but serious and have
      potentially life-threatening complications. It mostly involves the thoracic,
      abdominal and intracranial vessels. In this case study we describe the first
      reported case of spontaneous intestinal haematoma in a young male patient. The
      first episode occurred at the age of 30, following which 2 years later the second
      episode was noted at the same anatomical site, which was spontaneous without any
      inciting event.

PMID- 23975921
TI  - Unusual cause of cholestatic jaundice in a patient with AIDS.
AB  - A 61-year-old man with AIDS on chronic highly active antiretroviral treatment
      (HAART) presented with lethargy and jaundice and was found to have abnormal liver
      function tests (LFTs). Investigations including viral/autoimmune markers and
      imaging were unrevealing, except for positive Epstein-Barr virus. HAART was held,
      however, transaminases and total bilirubin continued to rise. The liver biopsy
      revealed classical Hodgkin's lymphoma (HL). HL presenting only with liver
      findings without lymphadenopathy is rare. Extreme cases can lead to fulminant
      liver failure. The bone marrow biopsy and dramatic elevation in serum ferritin
      were consistent with haemophagocytic lymphohistiocytosis. Finding a chemotherapy
      regimen was challenging given abnormal LFTs and HAART interactions. Initial
      chemotherapy regimen has successfully decreased LFTs; however, it was limited by
      pancytopenia. The patient's regimen was changed, however second regimen was
      complicated by neuropathy. LFTs improved and the patient was able to receive the
      standard care chemotherapy for HL with significant clinical, laboratory and
      radiological improvement.

PMID- 23975922
TI  - Recurrent pneumatosis intestinalis in a patient with dermatomyositis.
AB  - A 51-year-old woman with dermatomyositis (DM) on chronic immunosuppressive
      therapy was hospitalised for evaluation of haematuria. Surprisingly, abdominal
      imaging demonstrated pneumoperitoneum and pneumatosis intestinalis (PI). Her
      abdominal examination and white cell count were normal, but she subsequently
      developed nausea and fever. Owing to concern for perforation, a hemicolectomy was
      performed. Pathology revealed PI without inflammatory, ischaemic or neoplastic
      features, and she recovered uneventfully. Her immunosuppressive therapy was
      discontinued. Six months later, a follow-up CT of the abdomen revealed recurrence
      of PI. As she was asymptomatic, she was managed conservatively with resolution of
      PI on subsequent imaging. PI is characterised by the presence of gas within the
      wall of the intestine. Its aetiology is often unclear but this case highlights
      the association between PI and both immunosuppressive therapy and DM. A review of
      PI in patients with DM suggests that clinically stable patients may be observed,
      while avoiding surgical intervention.

PMID- 23975923
TI  - Management of sublingual ulceration in a 12-month-old child.
AB  - The case of sublingual ulceration associated with erupted primary mandibular
      incisors in a 1-year-old child is presented. Sublingual ulceration is termed as
      Riga-Fede disease if the patient is less than 2 years old. Generally, the
      treatment methods for Riga-Fede's disease are discing and extraction of the
      traumatised teeth. Here, the child was treated with photo-polymerised composite
      resin coverage of the incisal edges of erupted mandibular incisors. The photo
      polymerised resin coverage proved to help in the rapid healing of the
      ulcerations.

PMID- 23975924
TI  - Lobar haemorrhagic mass in a young girl with neurofibromatosis type 1.

PMID- 23975925
TI  - Glenohumeral joint tuberculosis with multiple cold abscesses: an uncommon cause
      of shoulder pain.
AB  - The musculoskeletal system involvement of tuberculosis (TB) other than spinal TB
      is a rare and less-known entity. Furthermore symptoms of musculoskeletal
      involvement of TB infection are non-specific, relatively slow and indolent. The
      diagnosis of TB is less considered by clinicians among other common causes of
      shoulder pain including traumatic and degenerative conditions. We reported a 72
      year-old patient suffering shoulder pain for the last 2 years who was diagnosed
      with glenohumeral joint TB arthritis associated with multiple cold abscesses in
      adjacent soft tissues; emphasising significant clinical and imaging findings.

PMID- 23975927
TI  - Illuminating the black box of B12 biosynthesis.

PMID- 23975926
TI  - Anti-inflammatory and immunomodulatory properties of alpha1-antitrypsin without
      inhibition of elastase.
AB  - The rationale of alpha1-antitrypsin (AAT) augmentation therapy to treat
      progressive emphysema in AAT-deficient patients is based on inhibition of
      neutrophil elastase; however, the benefit of this treatment remains unclear. Here
      we show that clinical grade AAT (with elastase inhibitory activity) and a
      recombinant form of AAT (rAAT) without anti-elastase activity reduces lung
      inflammatory responses to LPS in elastase-deficient mice. WT and elastase
      deficient mice treated with either native AAT or rAAT exhibited significant
      reductions in infiltrating neutrophils (23% and 68%), lavage fluid levels of TNF
      alpha (70% and 80%), and the neutrophil chemokine KC (CXCL1) (64% and 90%),
      respectively. Lung parenchyma TNF-alpha, DNA damage-inducible transcript 3 and X
      box binding protein-1 mRNA levels were reduced in both mouse strains treated with
      AAT; significantly lower levels of these genes, as well as IL-1beta gene
      expression, were observed in lungs of AAT-deficient patients treated with AAT
      therapy compared with untreated patients. In vitro, LPS-induced cytokines from WT
      and elastase-deficient mouse neutrophils, as well as neutrophils of healthy
      humans, were similarly reduced by AAT or rAAT; human neutrophils adhering to
      endothelial cells were decreased by 60-80% (P < 0.001) with either AAT or rAAT.
      In mouse pancreatic islet macrophages, LPS-induced surface expression of MHC II,
      Toll-like receptor-2 and -4 were markedly lower (80%, P < 0.001) when exposed to
      either AAT or rAAT. Consistently, in vivo and in vitro, rAAT reduced inflammatory
      responses at concentrations 40- to 100-fold lower than native plasma-derived AAT.
      These data provide evidence that the anti-inflammatory and immunomodulatory
      properties of AAT can be independent of elastase inhibition. 

PMID- 23975928
TI  - Discovery of the cellular and molecular basis of cholesterol control.
AB  - The cellular control of cholesterol metabolism mediated by lipoproteins was first
      appreciated in pioneering work published in a 1974 PNAS Classic by Michael Brown
      and Joseph Goldstein. We know from this paper that the LDL binds to a cell
      surface receptor and dampens the activity of a key enzyme in cholesterol
      biosynthesis and that a receptor deficiency is responsible for a major genetic
      cause of hypercholesterolemia and premature atherosclerosis. 

PMID- 23975929
TI  - A cold, hard look at ancient oxygen.

PMID- 23975930
TI  - A flexible polyglutamine hinge opens new doors for understanding huntingtin
      function.

PMID- 23975931
TI  - Small molecules mediate bacterial farming by social amoebae.

PMID- 23975932
TI  - DMD transcript imbalance determines dystrophin levels.
AB  - Duchenne and Becker muscular dystrophies are caused by out-of-frame and in-frame
      mutations, respectively, in the dystrophin encoding DMD gene. Molecular therapies
      targeting the precursor-mRNA are in clinical trials and show promising results.
      These approaches will depend on the stability and expression levels of dystrophin
      mRNA in skeletal muscles and heart. We report that the DMD gene is more highly
      expressed in heart than in skeletal muscles, in mice and humans. The transcript
      mutated in the mdx mouse model shows a 5' to 3' imbalance compared with that of
      its wild-type counterpart and reading frame restoration via antisense-mediated
      exon skipping does not correct this event. We also report significant transcript
      instability in 22 patients with Becker dystrophy, clarifying the fact that
      transcript imbalance is not caused by premature nonsense mutations. Finally, we
      demonstrate that transcript stability, rather than transcriptional rate, is an
      important determinant of dystrophin protein levels in patients with Becker
      dystrophy. We suggest that the availability of the complete transcript is a key
      factor to determine protein abundance and thus will influence the outcome of mRNA
      targeting therapies.

PMID- 23975933
TI  - When is education a disservice?
AB  - A surplus of Ph.D. graduates and cuts in funding risks the future of science. In
      fact, several recent surveys indicate that the Ph.D. job market in relevant
      science fields is in a state of contracture, yet many universities continue to
      maintain or even expand Ph.D. programs. An assessment of job advertisements in
      the journal Science supports the survey conclusions and suggests that advertising
      for tenure-track faculty positions as well as postdoctoral opportunities have
      both significantly declined since the 2008 financial collapse, leaving few
      opportunities for recent Ph.D. graduates in traditional career tracks. Incentives
      to expand Ph.D. programs continue to influence university administration despite
      their detrimental effects on students and possibly to the field. Active
      mentoring, however, could help establish less-is-more programs that benefit
      students and universities while maintaining the necessary stream of trainees
      critical to the future of science. Such programs would also require significant
      changes to university administration that may be unpopular, but are likely
      inevitable.

PMID- 23975934
TI  - LGR4 expressed in uterine epithelium is necessary for uterine gland development
      and contributes to decidualization in mice.
AB  - In previous work we generated mice with a tissue specific ablation of a leucine
      rich repeat containing G-protein-coupled receptor 4 (Lgr4) using the Keratin-5
      (K5) Cre transgenic mouse strain (Lgr4(K5 KO)). Interestingly, the Lgr4(K5 KO)
      female mice were subfertile, and their embryos had impaired development. Notably,
      the contributions of uterine development to the subfertility phenotype were not
      elucidated in the previous report. In a readdress, the following study explores
      uterine aberration in Lgr4(K5 KO) female mice. Histological analysis revealed
      that the uteri of Lgr4(K5 KO) mice displayed altered epithelial differentiation
      characterized by a reduction in the number of uterine glands. Furthermore, Lgr4
      deletion led to the reduced expression of morphoregulatory genes related to the
      Wnt signaling pathway. Additionally, the uteri of the Lgr4(K5 KO) mice lost the
      ability to undergo induced decidualization. Quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) analysis and administration of recombinant
      leukemia inhibitory factor (LIF) demonstrated that the impaired decidualization
      in Lgr4(K5 KO) mice resulted from the decreased secretion of LIF concurrent with
      a reduction in uterine gland count. Thus, we propose that LGR4 contributes to
      uterine gland development, which supports decidualization during pregnancy.

PMID- 23975935
TI  - NAD+ acts on mitochondrial SirT3 to prevent axonal caspase activation and axonal
      degeneration.
AB  - In chronic degenerative syndromes, neuronal death occurs over long periods,
      during which cells progressively lose their axons and, ultimately, their cell
      bodies. Although apoptosis is recognized as a key event in neuronal death, the
      molecular mechanisms involved in CNS axons degeneration are poorly understood.
      Due to the highly polarized phenotypes of CNS neurons, the different neuronal
      subcompartments are likely to be targeted by light repetitive and localized
      aggression. Such locally initiated deleterious signal transduction pathways could
      theoretically spread through the cytoplasm. However, where axon-degenerative
      signals initiate, what these early signals are, and how they lead to axon
      degeneration are unanswered questions that limit our understanding of
      neurodegenerative diseases and our ability to identify novel therapeutic targets.
      Using a microfluidic culture device adapted to CNS primary neurons, allowing
      specific access to the axonal and somatodendritic compartments, we analyzed the
      molecular pathways involved in axonal degeneration of differentiated neurons. We
      show here that local application of proapoptotic stimuli on the somatodentritic
      compartment triggers a dying-back pattern involving caspase-dependent axonal
      degeneration. Using complementary pharmacological and genetic approaches, we
      further demonstrate that NAD(+) and grape wine polyphenols prevent axonal
      apoptosis and act via mitochondrial SirT3 activation in axons.

PMID- 23975937
TI  - A conserved N-terminal motif is required for complex formation between FUS,
      EWSR1, TAF15 and their oncogenic fusion proteins.
AB  - The three FET (FUS, EWSR1, and TAF15) family RNA binding proteins are expressed
      in all tissues and almost all cell types. The disordered N-terminal parts are
      always present in FET fusion oncoproteins of sarcomas and leukemia. Mutations in
      FUS and TAF15 cause aggregation of FET proteins in neurological disorders. Here
      we used recombinant proteins in pulldown experiments and mass spectrometry to
      identify major interaction partners of the FET N-terminal parts. We report that
      FUS, EWSR1, and TAF15 form homo- and heterocomplexes as major binding partners
      and identify an evolutionarily conserved N-terminal motif (FETBM1) that is
      required for this interaction. The binding is RNA and DNA independent and robust
      up to 1 M of NaCl. The localization of FETBM1 and its target sequences supports a
      simple model for FET protein aggregation as reported in neurological disorders
      such as amyotrophic lateral sclerosis, frontotemporal dementia, and essential
      tremor. The FETBM1 localization also explains the binding of normal full-length
      FET proteins to their oncogenic fusion proteins.

PMID- 23975936
TI  - Retinoic acid-dependent regulation of miR-19 expression elicits vertebrate axis
      defects.
AB  - Retinoic acid (RA) is involved in multifarious and complex functions necessary
      for vertebrate development. RA signaling is reliant on strict enzymatic
      regulation of RA synthesis and metabolism. Improper spatiotemporal expression of
      RA during development can result in vertebrate axis defects. microRNAs (miRNAs)
      are also pivotal in orchestrating developmental processes. While mechanistic
      links between miRNAs and axial development are established, the role of miRNAs in
      regulating metabolic enzymes responsible for RA abundance during axis formation
      has yet to be elucidated. Our results uncovered a role of miR-19 family members
      in controlling RA metabolism through the regulation of CYP26A1 during vertebrate
      axis formation. Global miRNA expression profiling showed that developmental RA
      exposure suppressed the expression of miR-19 family members during zebrafish
      somitogenesis. A reporter assay confirmed that cyp26a1 is a bona fide target of
      miR-19 in vivo. Transient knockdown of miR-19 phenocopied axis defects caused by
      RA exposure. Exogenous miR-19 rescued the axis defects induced by RA exposure.
      Taken together, these results indicate that the teratogenic effects of RA
      exposure result, in part, from repression of miR-19 expression and subsequent
      misregulation of cyp26a1. This highlights a previously unidentified role of miR
      19 in facilitating vertebrate axis development via regulation of RA signaling.

PMID- 23975941
TI  - 'Floating' left atrial appendage in an infant with chylopericardium.

PMID- 23975943
TI  - Retraction. Maxillary adenomatoid odontogenic tumour.

PMID- 23975942
TI  - Retraction. A rare occurrence of peripheral ossifying fibroma in the first decade
      of life and its management.

PMID- 23975944
TI  - Contributions of neuroscience to the study of socioeconomic health disparities.
AB  - Socioeconomic disadvantage confers risk for ill health. Historically, the
      pathways by which socioeconomic disadvantage may affect health have been viewed
      from epidemiological perspectives emphasizing environmental, behavioral, and
      biopsychosocial risk factors. Such perspectives, however, have yet to integrate
      findings from emerging neuroscience studies demonstrating that indicators of
      socioeconomic disadvantage relate to patterns of brain morphology and
      functionality that have been associated with aspects of mental, physical, and
      cognitive health over the lifecourse. This commentary considers findings from one
      such study appearing in the current issue of Psychosomatic Medicine. It reports
      that an area-level indicator of socioeconomic disadvantage relates to cortical
      morphology in brain regions important for language, executive control, and other
      cognitive and behavioral functions-possibly via a systemic inflammatory pathway.
      These findings are put into context by discussing broader questions and
      challenges that need to be addressed in order for neuroscience approaches to a)
      become better integrated with existing epidemiological perspectives and b) more
      fully advance our understanding of the pathways by which socioeconomic
      disadvantage becomes embodied by the brain in relation to health. 

PMID- 23975945
TI  - Pre-hospital discharge testing of defibrillator without anesthesia: effects on
      psychological symptoms during clinical follow-up.
AB  - OBJECTIVE: After the implantation of an implantable cardioverter-defibrillator
      (ICD), patients often fear therapeutic shock. The extent to which the experience
      of pre-hospital discharge (PHD) testing without anesthesia after ICD
      implantation, under observation by a physician, affects shock-related anxiety
      symptoms on follow-up has not been investigated as yet. METHODS: In a
      prospective, randomized controlled trial, 44 patients with a primary prevention
      indication for an ICD were randomly assigned to experience PHD testing without
      anesthesia (n = 23) or with anesthesia (n = 21). Patients were longitudinally
      evaluated before (T(1)), shortly after (T(2)), and 3 months after (T(3)) PHD
      testing. During the respective PHD testings, the course of patients' serum
      cortisol release was measured. RESULTS: During PHD testing, patients without
      anesthesia showed a significantly higher serum cortisol release than patients
      with anesthesia (F(4,152) = 22.227, p < .001). Patients who experienced PHD
      testing without anesthesia felt significantly safer with the ICD (U = 165.000, p
      = .040), would significantly more often recommend other patients to undergo PHD
      testing without anesthesia (chi(2) = 12.013, p = .002), and showed significantly
      lower levels of general shock-related anxiety shortly afterward (F(1,42) = 6.327,
      p = .02) and 3 months after PHD testing (F(1,41) = 8.603, p = .005). CONCLUSIONS:
      The implementation of PHD testing without anesthesia is associated with lower
      anxiety concerning therapeutic shock. Patients should be advised about the
      effects of PHD testing without anesthesia on their psychological well-being in
      the long run.

PMID- 23975946
TI  - Socioeconomic deprivation and cortical morphology: psychological, social, and
      biological determinants of ill health study.
AB  - OBJECTIVE: Neighborhood-level socioeconomic deprivation has been associated with
      poor cognitive function pertaining to language and the executive control. Few
      studies have explored the cortical morphology of regions most commonly associated
      with these functions. The aim of this study was to examine the association
      between neighborhood-level deprivation and the morphology of cortical regions
      associated with language and executive control in adults. METHODS: Using a cross
      sectional study design, we compared the cortical morphology of 42 neurologically
      healthy adult men from the least deprived and most deprived neighborhoods of
      Glasgow. We performed surface-based morphometry on 3-T structural magnetic
      resonance imaging (MRI) images to extract the cortical morphology--volume,
      thickness (CT), and surface area (SA) of regions commonly associated with
      language and executive control. Cortical morphology was compared between the two
      groups. We used mediation analysis to examine whether cardiometabolic risk
      factors mediated the relationship between deprivation status and cortical
      morphology. RESULTS: Intracranial volume and mean total CT did not differ between
      groups. The deprived group had significantly smaller left posterior parietal
      cortex SA (Cohen d = 0.89) and fusiform cortex SA (Cohen d = 1.05). They also had
      thinner left Wernicke's area (Cohen d =0.93) and its right homologue (Cohen d =
      1.12). Among the cardiometabolic markers, a composite factor comprising
      inflammatory markers mediated the relationship between deprivation status and
      Wernicke's area CT. CONCLUSIONS: A group of neurologically healthy men from
      deprived neighborhoods showed significantly smaller cortical morphology--both SA
      and CT--in regions of the brain pertaining to language and executive function. We
      provide additional evidence of a relationship between socioeconomic deprivation
      and cortical morphology.

PMID- 23975947
TI  - Prospective analysis of association between statin use and breast cancer risk in
      the women's health initiative.
AB  - BACKGROUND: Statins are a class of cholesterol-lowering drugs that affect many
      intracellular pathways that may have implications for chemoprevention against
      cancer. Epidemiologic data on statins and breast cancer are conflicting. We
      analyzed updated data from the Women's Health Initiative (WHI) to assess the
      relationship between statins and breast cancer risk. METHODS: The population
      included 154,587 postmenopausal women ages 50 to 79 years, with 7,430
      pathologically confirmed cases of breast cancer identified over an average of
      10.8 (SD, 3.3) years. Information on statins was collected at baseline and years
      one, three, six, and nine. Self- and interviewer-administered questionnaires were
      used to collect information on risk factors. Cox proportional hazards regression
      was used to calculate HRs with 95% confidence intervals (CI) to evaluate the
      relationship between statin use and cancer risk. Statistical tests were two
      sided. RESULTS: Statins were used by 11,584 (7.5%) women at baseline. The
      annualized rate of breast cancer was 0.42% among statin users and 0.42% among
      nonusers. The multivariable adjusted HR of breast cancer for users versus
      nonusers was 0.94 (95% CI, 0.83-1.06). In the multivariable-adjusted, time
      dependent model, the HR for simvastatin was 0.87 (95% CI, 0.71-1.07). There was
      no significant trend by overall duration of use (P value for trend 0.68). There
      was no effect of tumor stage, grade, or hormone receptor status. CONCLUSION:
      Overall, statins were not associated with breast cancer risk. IMPACT: Our study
      is one of the largest prospective observational studies on this topic, and
      substantially adds to the literature suggesting no relationship between statins
      and breast cancer risk.

PMID- 23975951
TI  - Islam and the four principles of medical ethics.
AB  - The principles underpinning Islam's ethical framework applied to routine clinical
      scenarios remain insufficiently understood by many clinicians, thereby
      unfortunately permitting the delivery of culturally insensitive healthcare.This
      paper summarises the foundations of the Islamic ethical theory, elucidating the
      principles and methodology employed by the Muslim jurist in deriving rulings in
      the field of medical ethics. The four-principles approach, as espoused by
      Beauchamp and Childress, is also interpreted through the prism of Islamic ethical
      theory. Each of the four principles (beneficence, nonmaleficence,justice and
      autonomy) is investigated in turn, looking in particular at the extent to which
      each is rooted in the Islamic paradigm. This will provide an important insight
      into Islamic medical ethics, enabling the clinician to have a better informed
      discussion with the Muslim patient. It will also allow for a higher degree of
      concordance in consultations and consequently optimise culturally sensitive
      healthcare delivery.

PMID- 23975948
TI  - Cortical activation to action perception is associated with action production
      abilities in young infants.
AB  - The extent to which perception and action share common neural processes is much
      debated in cognitive neuroscience. Taking a developmental approach to this issue
      allows us to assess whether perceptual processing develops in close association
      with the emergence of related action skills within the same individual. The
      current study used functional near-infrared spectroscopy (fNIRS) to investigate
      the perception of human action in 4- to 6-month-old human infants. In addition,
      the infants' manual dexterity was assessed using the fine motor component of The
      Mullen Scales of Early Learning and an in-house developed Manual Dexterity task.
      Results show that the degree of cortical activation, within the posterior
      superior temporal sulcus--temporoparietal junction (pSTS-TPJ) region, to the
      perception of manual actions in individual infants correlates with their own
      level of fine motor skills. This association was not fully explained by either
      measures of global attention (i.e., looking time) or general developmental stage.
      This striking concordance between the emergence of motor skills and related
      perceptual processing within individuals is consistent with experience-related
      cortical specialization in the developing brain.

PMID- 23975952
TI  - Sexism and human enhancement.

PMID- 23976766
TI  - Assessment of the physicochemical stability of all-in-one parenteral emulsions
      for neonates according to USP specifications.
AB  - BACKGROUND: The purpose of this study was to describe the methodology to assess
      the stability of all-in-one (AIO) parenteral nutrition admixtures, containing
      glucose, proteins, and lipids, to the standards of U.S. Pharmacopoeia (USP
      <729>). The influence of calcium and commercially available lipid emulsions and
      amino acid solutions were also examined. METHODS: Four batches of 5 AIO
      admixtures containing calcium were compounded with commercially available lipid
      emulsions and amino acid solutions. Two of them contained calcium. Their
      stability was tested under conditions simulating clinical use. All the admixtures
      were assessed for criteria set by the USP <729>: (1) mean droplet diameter (MDD)
      and (2) percentage of volume weighted particles with diameter > 5 MUm (PFAT5).
      RESULTS: All admixtures were within the specifications set by the USP with
      respect to the MDD at 0, 24, and 48 hours, but only those batches lacking calcium
      met the benchmarks set by the pharmacopoeia, with respect to PFAT5, on the day of
      preparation. CONCLUSIONS: The presence of calcium destabilized the admixtures,
      while the use of different commercial ingredients altered the admixtures'
      characteristics. Only 1 batch of the AIO admixtures studied was found to be
      compliant with USP <729> standards.

PMID- 23976767
TI  - Exploitation of diagnostic computed tomography scans to assess the impact of
      nutrition support on body composition changes in respiratory failure patients.
AB  - BACKGROUND: Assessment of nutritional status in intensive care unit (ICU)
      patients is limited. Computed tomography (CT) scans that include the first to
      fifth lumbar region completed for diagnostic purposes measures fat and lean body
      mass (LBM) depots and are frequently done in ICU populations and can be used to
      quantify fat and LBM depots. The purpose of this study was to assess if these
      scans could measure change in skeletal muscle (SKT), visceral adipose (VAT), and
      intermuscular adipose (IMAT) tissue and to examine the association between the
      amount of energy and protein received and changes in these depots. METHODS: Cross
      sectional area of SKT, VAT, and IMAT from CT scans at the third lumbar region was
      quantified at 2 time points (CT1 and CT2). Change scores between CT1 and CT2 for
      each of these depots and the percentage of estimated energy/protein needs
      received were determined in 33 adults that with acute respiratory failure.
      Descriptive statistics and multiple regression was used to evaluate the influence
      of baseline characteristics and the percentage energy/protein needs received
      between CT1 and CT2 on percentage change/day between CT1 and CT2 on SKM, IMAT,
      and VAT. RESULTS: Participants were on average (SD) 59.7 (16) years old, received
      41% of energy and 57% of protein needs. The average time between CT1 and CT2 was
      10 (5) days. SKM declined 0.49%/day (men P = .07, women P = .09) and percentage
      of energy needs received reduced loss (beta = 0.024, P = .03). No change in VAT
      or IMAT occurred. CONCLUSIONS: CT scans can be exploited to assess change in body
      composition in ICU patients and may assist in detecting the causal link between
      nutritional support and outcomes in future clinical trials.

PMID- 23976768
TI  - Serum transthyretin level is associated with clinical severity rather than
      nutrition status in massively burned patients.
AB  - BACKGROUND: The purpose of this study is to clarify the clinical significance of
      serum transthyretin (TTR) in massively burned patients in nutrition support and
      clinical severity. METHODS: A retrospective study was performed with 204 patients
      admitted to Hangang Sacred Heart Hospital's Burn Center September 2010-September
      2012 with burn wounds > 20% of total body surface area (TBSA) burned. Serum TTR,
      C-reactive protein (CRP), lactic acid, and an NST index (calculated by dividing
      real caloric intake by estimated caloric need for 7 days) were analyzed on a
      weekly basis for 5 weeks after admission. RESULTS: When we classified patients
      with severity according to mortality, percentage of TBSA burned, serum lactic
      acid, and CRP, mean serum TTR level was significantly higher in the less severe
      patient group than in the severe patient group in each week for every severity
      index. And the serum TTR level did not show significant differences by NST index
      in both the severe patient group and the less severe patient group. In a
      multivariate logistic regression, percentage TBSA burned, TTR, and lactic acid
      had an independent association with mortality. CONCLUSION: Serum TTR did not show
      a significant difference by nutrition support in massively burned patients with
      >20% of TBSA burned. But serum TTR was significantly different by the severity of
      the patient and independently associated with mortality. Hence, serum TTR level
      can be 1 of the useful biomarkers for comprehending the severity of the illness
      in massively burned patients.

PMID- 23976769
TI  - A.S.P.E.N. Clinical guidelines: nutrition support of hospitalized adult patients
      with obesity.
AB  - BACKGROUND: Due to the high prevalence of obesity in adults, nutrition support
      clinicians are encountering greater numbers of obese patients who require
      nutrition support during hospitalization. The purpose of this clinical guideline
      is to serve as a framework for the nutrition support care of adult patients with
      obesity. METHOD: A systematic review of the best available evidence to answer a
      series of questions regarding management of nutrition support in patients with
      obesity was undertaken and evaluated using concepts adopted from the Grading of
      Recommendations, Assessment, Development and Evaluation working group. A
      consensus process, that includes consideration of the strength of the evidence
      together with the risks and benefits to the patient, was used to develop the
      clinical guideline recommendations prior to multiple levels of external and
      internal review and approval by the A.S.P.E.N. Board of Directors. QUESTIONS: (1)
      Do clinical outcomes vary across levels of obesity in critically ill or
      hospitalized non-intensive care unit (ICU) patients? (2) How should energy
      requirements be determined in obese critically ill or hospitalized non-ICU
      patients? (3) Are clinical outcomes improved with hypocaloric, high protein diets
      in hospitalized patients? (4) In obese patients who have had a malabsorptive or
      restrictive surgical procedure, what micronutrients should be evaluated?

PMID- 23976770
TI  - Frequency of aspirating gastric tubes for patients receiving enteral nutrition in
      the ICU: a randomized controlled trial.
AB  - BACKGROUND: Enteral nutrition (EN) tolerance is often monitored by aspirating
      stomach contents by syringe at prescribed intervals. No studies have been
      conducted to assess the most appropriate time interval for aspirating gastric
      tubes. We compared gastric tube aspirations every 4 hours (usual care) with a
      variable regimen (up to every 8 hours aspirations). METHODS: This randomized
      controlled trial (RCT) enrolled patients who stayed in the intensive care unit
      (ICU) for >48 hours, had a gastric tube, and were likely to receive EN for 3 or
      more days. Patients were randomized (computer-generated randomization) to either
      the control (every 4 hours) or intervention group (variable regimen). The primary
      outcome was number of gastric tube aspirations per day from randomization until
      EN was ceased or up to 2 weeks postrandomization. RESULTS: Following
      Institutional Ethics Committee approval, 357 patients were recruited (control
      group, n = 179; intervention group, n = 178). No differences were found in age,
      sex, worst APACHE II score, or time to start of EN. In the intention-to-treat
      analysis, the intervention group had fewer tube aspirations per day (3.4 versus
      5.4 in the control group, P < .001). Vomiting/regurgitation was increased in the
      intervention group (2.1% versus 3.6%, P = .02). There were no other differences
      in complications. CONCLUSION: This is the first RCT to examine the frequency of
      gastric tube aspirations. The frequency of gastric tube aspirations was reduced
      in the variable-regimen group with no increase in risk to the patient. Reducing
      the frequency of aspirations saves nursing time, decreases risk of contamination
      of feeding circuit, and minimizes risk of body fluid exposure.

PMID- 23976772
TI  - Complex dietary protein improves growth through a complex mechanism of intestinal
      peptide absorption and protein digestion.
AB  - BACKGROUND: The small intestinal epithelium has an impressive ability to adapt to
      changes resulting from loss of length or alteration in dietary load. We sought to
      determine the potential influence of dietary protein absorption on growth and
      development. We hypothesized that a complex protein diet would improve growth
      over that of an elemental diet. METHODS: Using the nematode Caenorhabditis
      elegans, a transparent worm with a rudimentary intestinal tube lined by
      enterocytes that function remarkably similar to humans, we measured daily growth,
      intestinal peptide, and amino acid transporter expression and intestinal
      proteolysis to compare the effects of a complex protein diet to a diet containing
      only amino acids. RESULTS: Nematodes raised on a complex protein diet grew to
      adulthood faster than those raised solely on amino acids, which did not require
      an overall change in intestinal peptide or amino acid transporter expression.
      Despite no overall change in transporter expression, a shift in location of
      peptide transporter expression was noted between diets that corresponded to
      decreased rate of intestinal proteolysis seen in the complex protein-fed group.
      CONCLUSIONS: A complex protein diet stimulates in an altered pattern of
      intestinal peptide transporter expression and intestinal proteolytic activity
      that results in improved growth compared with a diet of elemental amino acids.
      This improved growth appears to be the result of increased efficiency of a
      smaller number of enterocytes. These data might be useful in targeting intestinal
      rehabilitation therapies for short bowel syndrome and other risk factors for
      intestinal failure.

PMID- 23976771
TI  - The effect of a low fructose and low glycemic index/load (FRAGILE) dietary
      intervention on indices of liver function, cardiometabolic risk factors, and body
      composition in children and adolescents with nonalcoholic fatty liver disease
      (NAFLD).
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common liver disease in
      obese children. Diets high in added fructose (high fructose corn syrup; HFCS) and
      glycemic index (GI)/glycemic load (GL) are associated with increased risk of
      NAFLD. Lifestyle modification is the main treatment, but no guidelines regarding
      specific dietary interventions for childhood NAFLD exist. We hypothesized that
      reductions in dietary fructose (total, free, and HFCS)/GI/GL over 6 months would
      result in improvements in body composition and markers of liver dysfunction and
      cardiometabolic risk in childhood NAFLD. METHODS: Children and adolescents with
      NAFLD (n = 12) and healthy controls (n = 14) 7-18 years were studied at baseline
      and 3 and 6 months post-dietary intervention. Plasma markers of liver dysfunction
      (ALT, AST, gammaGT), cardiometabolic risk (TG, total cholesterol, LDL-HDL
      cholesterol, Apo-B100, Apo-B48, Apo-CIII, insulin, homeostasis model of
      assessment of insulin resistance [HOMA-IR]), inflammation (TNF-alpha, IL-6, IL
      10), anthropometric, and blood pressure (BP) were studied using validated
      methodologies. RESULTS: Significant reductions in systolic BP (SBP), percentage
      body fat (BF), and plasma concentrations of ALT (P = .04), Apo-B100 (P < .001),
      and HOMA-IR were observed in children with NAFLD at 3 and 6 months (P < .05).
      Dietary reductions in total/free fructose/HFCS and GL were related to reductions
      in SBP (P = .01), ALT (P = .004), HOMA-IR (P = .03), and percentage BF in
      children with NAFLD. Reductions in dietary GI were associated with reduced plasma
      Apo-B100 (P = .02) in both groups. With the exception of Apo-B100, no changes in
      laboratory variables were observed in the control group. CONCLUSION: Modest
      reductions in fructose (total/free, HFCS) and GI/GL intake result in improvements
      of plasma markers of liver dysfunction and cardiometabolic risk in childhood
      NAFLD.

PMID- 23976774
TI  - Nutrition therapy for the critically ill surgical patient with aortic aneurysmal
      rupture: defining and improving current practice.
AB  - BACKGROUND: Our goal is to define nutrition therapy in critically ill patients
      after surgical repair of acute ruptured or dissecting aortic aneurysm to identify
      opportunities for quality improvement. METHODS: International, prospective
      studies in 2007-2009 and 2011 were combined. Sites provided institutional and
      patient characteristics including from intensive care units (ICUs) admission to
      ICU discharge for a maximum of 12 days. We selected patients with aortic
      aneurysmal rupture or acute dissection staying in the ICU for >= 3 days. RESULTS:
      There were 104 eligible patients from 72 distinct ICUs analyzed. Overall, 86.5%
      received artificial nutrition. There were 50.0% patients who received enteral
      nutrition (EN) only, 29.8% patients received a combination of EN and parenteral
      nutrition (PN), 6.7% patients received PN only, and 13.5% did not receive any
      nutrition. The mean time from admission to initiation of EN was 3.0 days (SD +/-
      2.4 days). The adequacy of calories from nutrition support was 46.8% (range 0%
      111%) with a mean of 10.0 kcal/kg/day. Of the total of 83 patients who received
      EN, 53 patients (63.8%) had interruption of EN. The reasons included fasting,
      intolerance, patients deemed too sick for enteral feeding, and loss of enteral
      feeding route. For patients with gastrointestinal intolerance, 3/30 patients
      (10%) received small bowel feeding and 23/30 patients (76.7%) of patients
      received motility agents. CONCLUSION: Postoperative critically ill patients with
      aortic aneurysmal rupture or acute dissection are at high risk for inadequate
      nutrition therapy, and there may be inadequate utilization of strategies to
      improve nutrition uptake.

PMID- 23976773
TI  - Decreased bone turnover markers in children on long-term parenteral nutrition
      (PN) for intestinal failure (IF).
AB  - BACKGROUND: Metabolic bone disease (MBD) is a well-recognized but poorly
      understood complication of long-term parenteral nutrition (PN). Bone
      histomorphometry in adults has provided useful information but does not provide
      quantitative measures of bone resorption and is to invasive for children.
      Measurement of bone turnover markers provides an alternative less invasive
      approach. We therefore aimed to measure bone turnover markers in children on long
      term PN for intestinal failure (IF), and to compare them to age- and gender
      matched controls. METHODS: Serum concentrations of osteocalcin (OC), bone
      specific alkaline phosphatase (BSAP), and c-telopeptide (CTx) were measured in IF
      patients treated at a multidisciplinary intestinal rehabilitation and home PN
      program at the Hospital for Sick Children, Toronto, Canada. Age- and gender
      matched control participants were recruited for comparison. RESULTS: A total of
      13 IF patients and 20 control participants were recruited. IF patients had lower
      serum OC and CTx concentrations when compared with controls: 42.43 +/- 11.54 vs
      68.39 +/- 20.95 ug/L (P < .01) and 7.454 +/- 2.17 vs 9.246 +/- 1.92 (P < .05;
      mean +/- SD) ug/L for OC and CTx, respectively. In a subgroup of 9 IF patients
      for whom BMD was available, OC and CTx concentration were negatively correlated
      to BMD (g/cm(2)) and BMD z score. CONCLUSION: Bone turnover markers may be useful
      indicators for identifying children on long-term PN at risk of MBD. Further
      studies are needed to validate the current results and determine the factors that
      influence the occurrence and evolution of MBD in children on PN.

PMID- 23976775
TI  - The Future of Nursing report three years later: an interview with Susan B.
      Hassmiller, PhD, RN, FAAN, Senior Advisor for Nursing at the Robert Wood Johnson
      Foundation. Interview by Sally S. Cohen.

PMID- 23976776
TI  - The struggle of giving up personal goals: affective, physiological, and cognitive
      consequences of an action crisis.
AB  - A critical phase in goal striving occurs when setbacks accumulate and goal
      disengagement becomes an issue. This critical phase is conceptualized as an
      action crisis and assumed to be characterized by an intrapsychic conflict in
      which the individual becomes torn between further goal pursuit and goal
      disengagement. Our theorizing converges with Klinger's conceptualization of goal
      disengagement as a process, rather than a discrete event. Two longitudinal field
      studies tested and found support for the hypothesis that an action crisis not
      only compromises an individual's psychological and physiological well-being, but
      also dampens the cognitive evaluation of the respective goal. In Study 3,
      marathon runners experiencing an action crisis in their goal of running marathons
      showed a stronger cortisol secretion and a lower performance in the race 2 weeks
      later. Results are interpreted in terms of action-phase-specific mindsets with a
      focus on self-regulatory processes in goal disengagement. 

PMID- 23976777
TI  - Maternal mortality in a rural Tanzanian hospital: fatal Jarisch-Herxheimer
      reaction in a case of relapsing fever in pregnancy.
AB  - Relapsing fever is a disease caused by one of the species of Borrelia. It is
      often misdiagnosed as malaria and can have fatal complications such as the
      Jarisch-Herxheimer reaction (JHR) after the commencement of treatment with
      antibiotics. A 19-year-old Tanzanian woman was admitted after a term home
      delivery that day. She presented with a 2 day history of fever, headache, general
      body malaise and vomiting. She was misdiagnosed as having severe malaria and was
      treated with quinine. The blood slide showed Borrelia duttoni. The patient
      continued treatment with procaine penicillin fortified for relapsing fever.
      Several hours later the woman died, probably due to JHR. This case of a patient
      with relapsing fever who died from a JHR stresses the importance of adequate
      diagnosis and treatment which should include careful monitoring, especially for
      the first hours after starting antibiotics. 

PMID- 23976778
TI  - Improving activity in adults with diabetes and coexisting obstructive sleep
      apnea.
AB  - This study in participants with type 2 diabetes and obstructive sleep apnea
      evaluated changes in activity, sleep quality, and daytime sleepiness after 4
      weeks of continuous positive airway pressure (CPAP). This pilot study was a
      double-blind, randomized, placebo-controlled trial. Sleep apnea was quantified
      with an overnight sleep study. Sleep quality was measured by the Pittsburgh Sleep
      Quality Index, daytime sleepiness by the Epworth Sleepiness Scale, vigor and
      fatigue with the Profiles of Mood States, subjective activity with the Functional
      Outcomes of Sleep Questionnaire, and objective activity with the Bodymedia
      SenseWear Armband. Subjects were randomized to either CPAP (n = 12) or sham
      devices (n = 11). The intervention group had reduced apneas and hypopneas,
      daytime sleepiness, and fatigue; they also had improved sleep quality and
      increased objective activity and vigor. The study suggested that treatment of
      obstructive sleep apnea results in a modest improvement of activity in persons
      with type 2 diabetes.

PMID- 23976780
TI  - Trainee concerns regarding the Specialty Certificate Examination: results of a
      British Thoracic Society national survey.

PMID- 23976779
TI  - Evaluation of screening methods for identification of patients with chronic
      rheumatological disease requiring tuberculosis chemoprophylaxis prior to
      commencement of TNF-alpha antagonist therapy.
AB  - BACKGROUND: Patients undergoing tumour necrosis factor (TNF)-alpha antagonist
      therapy are at increased risk of latent tuberculosis infection (LTBI)
      reactivation. The aim of this study was to determine the optimum available
      screening strategy for identifying patients for tuberculosis (TB)
      chemoprophylaxis. METHODS: We conducted a prospective observational study of
      consecutive adults with chronic rheumatological disease referred for LTBI
      screening prior to commencement of TNF-alpha antagonist therapy. All patients
      included had calculation of TB risk according to age, ethnicity and year of UK
      entry, as described in the 2005 British Thoracic Society (BTS) guidelines and
      measurement of tuberculin skin test (TST) and T.Spot.TB. RESULTS: There were 187
      patients included in the study, with 157 patients (84%) taking
      immunosuppressants. 137 patients would require further risk stratification
      according to the BTS algorithm, with 110 (80.3%) classified as being at low risk
      of having LTBI. There were 39 patients (35.5%) who were categorised as low risk
      but were either TST and/or T.Spot positive and would not have received
      chemoprophylaxis according to the BTS algorithm. Combination of all three methods
      (risk stratification and/or positive T.Spot and/or positive TST) identified 66
      patients out of 137 who would potentially be offered chemoprophylaxis, which was
      greater than any single test or two-test combination. CONCLUSION: Performing both
      a TST and T.Spot in patients on immunosuppressants prior to commencement of TNF
      alpha antagonist therapy gives an additional yield of potential LTBI compared
      with use of risk stratification tables alone. Our results suggest that use of all
      three screening modalities gives the highest yield of patients potentially
      requiring chemoprophylaxis.

PMID- 23976781
TI  - Accumulated polymer degradation products as effector molecules in cytotoxicity of
      polymeric nanoparticles.
AB  - Polymeric nanoparticles (PNPs) are a promising platform for drug, gene, and
      vaccine delivery. Although generally regarded as safe, the toxicity of PNPs is
      not well documented. The present study investigated in vitro toxicity of poly
      epsilon-caprolactone, poly(DL-lactic acid), poly(lactide-cocaprolactone), and
      poly(lactide-co-glycide) NPs and possible mechanism of toxicity. The
      concentration-dependent effect of PNPs on cell viability was determined in a
      macrophage (RAW 264.7), hepatocyte (Hep G2), lung epithelial (A549), kidney
      epithelial (A498), and neuronal (Neuro 2A) cell lines. PNPs show toxicity at high
      concentrations in all cell lines. PNPs were efficiently internalized by RAW 264.7
      cells and stimulated reactive oxygen species and tumor necrosis factor-alpha
      production. However, reactive nitrogen species and interleukin-6 production as
      well as lysosomal and mitochondrial stability remained unaffected. The
      intracellular degradation of PNPs was determined by monitoring changes in
      osmolality of culture medium and a novel fluorescence recovery after quenching
      assay. Cell death showed a good correlation with osmolality of culture medium
      suggesting the role of increased osmolality in cell death. 

PMID- 23976782
TI  - Aberration in epigenetic gene regulation in hippocampal neurogenesis by
      developmental exposure to manganese chloride in mice.
AB  - We have shown that maternal manganese (Mn) exposure caused sustained disruption
      of hippocampal neurogenesis of mouse offspring. To clarify the effects of
      maternal Mn exposure on epigenetic gene regulation contributing to the sustained
      disruption of hippocampal neurogenesis, we treated pregnant ICR mice with MnCl2
      in diet from gestational day 10 through day 21 after delivery on weaning and
      searched epigenetically downregulated genes by global promoter methylation
      analysis in the hippocampal dentate gyrus of male offspring on postnatal day
      (PND) 21 and PND 77. By CpG promoter microarray analysis on PND 21 following 800
      ppm Mn exposure, sustained promoter hypermethylation and transcript
      downregulation through PND 77 were confirmed with Mid1, Atp1a3, and Nr2f1,
      whereas Pvalb showed a transient hypermethylation only on weaning. The numbers of
      Pvalb+ and ATP1a3+ neurons suggestive of gamma-aminobutyric acid (GABA)ergic
      interneurons, Mid1+ cells suggestive of late-stage granule cell lineage and
      GABAergic interneurons, and COUP-TF1+ cells suggestive of early-stage granule
      cell lineage were all reduced on PND 21, and reductions were sustained on PND 77
      except for no change in Pvalb+ cells. Mid1+ cells showed asymmetric distribution
      with right-side predominance, and Mn exposure abolished it by promoter
      hypermethylation of the right side. These findings indicate epigenetic mechanisms
      as mediators, through which Mn exposure modulates neurogenesis involving both
      granule cell lineage and GABAergic interneurons with long-lasting and stable
      repercussions. Disruption of asymmetric cellular distribution of Mid1 suggests
      that higher brain functions specialized in the left or right side of the brain
      were affected.

PMID- 23976783
TI  - Intestinal schistosomiasis in pre school-aged children of Lake Albert, Uganda:
      diagnostic accuracy of a rapid test for detection of anti-schistosome antibodies.
AB  - BACKGROUND: A sensitive and reliable rapid diagnostic test (RDT) which should
      have comparable diagnostic performance against reference host serological methods
      is urgently needed for use in point-of-care (POC) diagnosis of intestinal
      schistosomiasis in pre school-aged children. METHODS: The diagnostic accuracy of
      a RDT incorporating Schistosoma mansoni cercarial transformation fluid (SmCTF)
      for anti-schistosome antibody detection was evaluated with serum samples from a
      cohort of children from Uganda: 42 children aged under the age of 3 years and 40
      children aged between 3 and 5 years. The infection status of these children had
      been previously determined by inspection of quadruplicate Kato-Katz faecal
      smears, a single urine circulating cathodic antigen (CCA) dipstick and antibody
      titres to S. mansoni soluble egg antigen (SmSEA) with a commercially available
      ELISA. RESULTS: Upon comparison with quadruplicate Kato-Katz the sensitivity and
      specificity of the RDT were 75.7% and 31.1%, respectively. When using the SmSEA
      ELISA as an alternate reference test, the RDT achieved 81.3% sensitivity and
      61.1% specificity. Sensitivity and specificity compared to the urine-CCA test was
      74.5% and 32.3% respectively. Sensitivity differed significantly according to age
      group. CONCLUSIONS: The performance of the RDT within this study appeared
      favourable when compared with the currently-available SmSEA-ELISA. Looking to the
      future a serological POC test would be particularly promising for use in disease
      mapping in younger children especially in guiding administration of praziquantel
      treatment in selective treatment settings.

PMID- 23976784
TI  - Increased detection of mastitis pathogens by real-time PCR compared to bacterial
      culture.
AB  - Rapid and accurate identification of mastitis pathogens is important for disease
      control. Bacterial culture and isolate identification is considered the gold
      standard in mastitis diagnosis but is time consuming and results in many culture
      negative samples. Identification of mastitis pathogens by PCR has been proposed
      as a fast and sensitive alternative to bacterial culture. The results of
      bacterial culture and PCR for the identification of the aetiological agent of
      clinical mastitis were compared. The pathogen identified by traditional culture
      methods was also detected by PCR in 98 per cent of cases indicating good
      agreement between the positive results of bacterial culture and PCR. A mastitis
      pathogen could not be recovered from approximately 30 per cent of samples by
      bacterial culture, however, an aetiological agent was identified by PCR in 79 per
      cent of these samples. Therefore, a mastitis pathogen was detected in
      significantly more milk samples by PCR than by bacterial culture (92 per cent and
      70 per cent, respectively) although the clinical relevance of PCR-positive
      culture-negative results remains controversial. A mixed infection of two or more
      mastitis pathogens was also detected more commonly by PCR. Culture-negative
      samples due to undetected Staphylococcus aureus infections were rare. The use of
      PCR technology may assist in rapid mastitis diagnosis, however, accurate
      interpretation of PCR results in the absence of bacterial culture remains
      problematic. 

PMID- 23976785
TI  - Mass-mortality in green striped tree dragons (Japalura splendida) associated with
      multiple viral infections.
AB  - In spring 2011, high mortality in association with skin lesions, systemic
      haemorrhages and necrosis occurred in a group of green striped tree dragons
      (Japalura splendida) which were imported from southwestern China via Florida to
      Germany. Infections with various endoparasites were diagnosed in coprological
      examinations. Different antiparasitic and antibiotic treatments over a period of
      three months did not reduce the mortality rate. The remaining animals were
      therefore euthanased and submitted for additional testing. Predominant findings
      in pathological examination were granulomatous and necrotising inflammation of
      the skin, vacuolar tubulonephrosis of the distal renal tubules, hyperaemia and
      liver necrosis. Eosinophilic intranuclear and basophilic intracytoplasmic
      inclusion bodies were detected in the liver. Virological testing (PCR and virus
      isolation methods) demonstrated the presence of ranavirus, adenovirus and
      invertebrate iridovirus. 

PMID- 23976786
TI  - Performance of Regular and Modified Canola and Soybean Oils in Rotational Frying.
AB  - Canola and soybean oils both regular and with modified fatty acid compositions by
      genetic modifications and hydrogenation were compared for frying performance. The
      frying was conducted at 185 +/- 5  degrees C for up to 12 days where French
      fries, battered chicken and fish sticks were fried in succession. Modified canola
      oils, with reduced levels of linolenic acid, accumulated significantly lower
      amounts of polar components compared to the other tested oils. Canola oils
      generally displayed lower amounts of oligomers in their polar fraction. Higher
      rates of free fatty acids formation were observed for the hydrogenated oils
      compared to the other oils, with canola frying shortening showing the highest
      amount at the end of the frying period. The half-life of tocopherols for both
      regular and modified soybean oils was 1-2 days compared to 6 days observed for
      high-oleic low-linolenic canola oil. The highest anisidine values were observed
      for soybean oil with the maximum reached on the 10th day of frying. Canola and
      soybean frying shortenings exhibited a faster rate of color formation at any of
      the frying times. The high-oleic low-linolenic canola oil exhibited the greatest
      frying stability as assessed by polar components, oligomers and non-volatile
      carbonyl components formation. Moreover, food fried in the high-oleic low
      linolenic canola oil obtained the best scores in the sensory acceptance
      assessment.

PMID- 23976787
TI  - Sensory Constraints on Birdsong Syntax: Neural Responses to Swamp Sparrow Songs
      with Accelerated Trill Rates.
AB  - Both sensory and motor mechanisms can constrain behavioral performance. Sensory
      mechanisms may be especially important for constraining behaviors that depend on
      experience, such as learned birdsongs. Swamp sparrows learn to sing by imitating
      the song of a tutor, but sparrows fail to accurately imitate artificial tutor
      songs with abnormally accelerated trills, instead singing brief and rapid trills
      interrupted by silent gaps. This "broken syntax" has been proposed to arise from
      vocal-motor limitations. Here we consider whether sensory limitations exist that
      could also contribute to broken syntax. We tested this idea by recording auditory
      evoked activity of sensorimotor neurons in the swamp sparrow's brain that are
      known to be important for the learning, performance and perception of song. In
      freely behaving adult sparrows that sang songs with normal syntax, neurons were
      detected that exhibited precisely time-locked activity to each repetition of the
      syllable in a trill when presented at a natural rate. Those cells failed to
      faithfully follow syllables presented at an accelerated rate, however, and their
      failure to respond to consecutive syllables increased as a function of trill
      rate. This "flickering" auditory representation in animals performing normal
      syntax reveals a central constraint on the sensory processing of rapid trills.
      Furthermore, because these neurons are implicated in both song learning and
      perception, and because auditory flickering began to occur at accelerated trill
      rates previously associated with the emergence of broken song syntax, these
      sensory constraints may contribute to the emergence of broken syntax.

PMID- 23976788
TI  - High-sweep-rate 1310 nm MEMS-VCSEL with 150 nm continuous tuning range.
AB  - Microelectromechanical-systems-based vertical-cavity surface-emitting lasers
      (MEMS-VCSELs) capable of a 150 nm continuous tuning range near 1310 nm are
      demonstrated. These devices employ a thin optically pumped active region
      structure with large free-spectral range, which promotes wide and continuous
      tuning. To achieve VCSEL emission at 1310 nm, a wide-gain-bandwidth indium
      phosphide-based multiple quantum well active region is combined with a wide
      bandwidth fully oxidised GaAs-based mirror through wafer bonding, with tuning
      enabled by a suspended dielectric top mirror. These devices are capable of being
      scanned over the entire tuning range at frequencies up to 500 kHz, making them
      ideal for applications such as swept source optical coherence tomography and high
      speed transient spectroscopy.

PMID- 23976789
TI  - A Single-Photon Avalanche Diode Array for Fluorescence Lifetime Imaging
      Microscopy.
AB  - We describe the design, characterization, and demonstration of a fully integrated
      single-photon avalanche diode (SPAD) imager for use in time-resolved fluorescence
      imaging. The imager consists of a 64-by-64 array of active SPAD pixels and an on
      chip time-to-digital converter (TDC) based on a delay-locked loop (DLL) and
      calibrated interpolators. The imager can perform both standard time-correlated
      single-photon counting (TCSPC) and an alternative gated-window detection useful
      for avoiding pulse pile-up when measuring bright signal levels. To illustrate the
      use of the imager, we present measurements of the decay lifetimes of fluorescent
      dyes of several types with a timing resolution of 350 ps.

PMID- 23976790
TI  - Simultaneous estimation and variable selection in median regression using Lasso
      type penalty.
AB  - We consider the median regression with a LASSO-type penalty term for variable
      selection. With the fixed number of variables in regression model, a two-stage
      method is proposed for simultaneous estimation and variable selection where the
      degree of penalty is adaptively chosen. A Bayesian information criterion type
      approach is proposed and used to obtain a data-driven procedure which is proved
      to automatically select asymptotically optimal tuning parameters. It is shown
      that the resultant estimator achieves the so-called oracle property. The
      combination of the median regression and LASSO penalty is computationally easy to
      implement via the standard linear programming. A random perturbation scheme can
      be made use of to get simple estimator of the standard error. Simulation studies
      are conducted to assess the finite-sample performance of the proposed method. We
      illustrate the methodology with a real example.

PMID- 23976791
TI  - The synthesis of biologically relevant conjugates of Re(CO)3 using pyridine-2
      carboxyaldehyde.
AB  - The new pyridine-2-carboxaldehyde adduct, Re(CO)3(NC6H5C(O)H)Cl 1, and previously
      reported complex Re(CO)3(NC6H5C(O)H)Br 2 react with aniline derivatives
      sulfanilamide or 4-aminofluorescein in methanol giving Schiff base conjugates
      Re(CO)3(pyca-R)X (pyca = pyridinecarbaldehyde imine, X = Cl, Br), 3-6. Pre
      isolation of compounds 1 and 2 provides a convenient method for preparing
      conjugate complexes in addition to the known methods of ligand synthesis and one
      pot reactions. All new compounds were completely characterized, and compound 1
      and the sulfanilamide derivatives 3 and 4 were structurally elucidated by X-ray
      crystallography.

PMID- 23976792
TI  - On the effect of prestrain and residual stress in thin biological membranes.
AB  - Understanding the difference between ex vivo and in vivo measurements is critical
      to interpret the load carrying mechanisms of living biological systems. For the
      past four decades, the ex vivo stiffness of thin biological membranes has been
      characterized using uniaxial and biaxial tests with remarkably consistent
      stiffness parameters, even across different species. Recently, the in vivo
      stiffness was characterized using combined imaging techniques and inverse finite
      element analyses. Surprisingly, ex vivo and in vivo stiffness values differed by
      up to three orders of magnitude. Here, for the first time, we explain this
      tremendous discrepancy using the concept of prestrain. We illustrate the
      mathematical modeling of prestrain in nonlinear continuum mechanics through the
      multiplicative decomposition of the total elastic deformation into prestrain
      induced and load-induced parts. Using in vivo measured membrane kinematics and
      associated pressure recordings, we perform an inverse finite element analysis for
      different prestrain levels and show that the resulting membrane stiffness may
      indeed differ by four orders of magnitude depending on the prestrain level. Our
      study motivates the hypothesis that prestrain is important to position thin
      biological membranes in vivo into their optimal operating range, right at the
      transition point of the stiffening regime. Understanding the effect of prestrain
      has direct clinical implications in regenerative medicine, medical device design,
      and and tissue engineering of replacement constructs for thin biological
      membranes.

PMID- 23976793
TI  - Effect of Linker Structure on Salicylic Acid-Derived Poly(anhydride-esters).
AB  - A series of salicylic acid-derived poly(anhydride-esters) were synthesized by
      melt polym erization methods, in which the structures of the molecule ("linker")
      linking together the two salicylic acids were varied. To determine the
      relationship between the linker and the physical properties of the corresponding
      poly(anhydride-ester), several linkers were evaluated including linear aliphatic,
      aromatic, and aliphatic branched structures. For the linear aliphatic linkers,
      higher molecular weights were obtained with longer linear alkyl chains. The most
      sterically hindered linkers yielded lower molecular weight polymers. The thermal
      decomposition temperature increased with the alkyl chain length, but the glass
      transition temperature decreased, due to the enhanced flexibility of the polymer.
      The highest glass transition temperatures were obtained by using aromatic linkers
      as a result of increased pi-pi interactions. Water contact angles determined the
      relative hydrophobicity of the polymers, which correlated to hydrolytic
      degradation rates; i.e., the highest contact angle values yielded the slowest
      degrading polymers.

PMID- 23976794
TI  - Entropy-enthalpy Compensation of Biomolecular Systems in Aqueous Phase: a Dry
      Perspective.
AB  - We survey thermodynamic measurements on processes involving biological
      macromolecules in aqueous solution, which illustrate well the ubiquitous
      phenomenon of entropy-enthalpy compensation. The processes include protein
      folding/unfolding and ligand binding/unbinding, with compensation temperatures
      varying by about 50 K around an average near 293 K. We show that incorporating
      both near-exact entropy-enthalpy compensation (due to solvent relaxation) and
      multi-excitation entropy (from vibrational quanta) leads to a compensation
      temperature in water of about 230 K. We illustrate a general procedure for
      subtracting solvent and environment-related terms to determine the bare Gibbs
      free energy changes of chemical processes.

PMID- 23976795
TI  - A Convenient Synthesis of gamma-Amino-Ynamides via Additions of Lithiated
      Ynamides to Aryl Imines. Observation of an Aza-Meyer-Schuster Rearrangement.
AB  - Efforts in developing an expeditious and convenient method for synthesizing gamma
      amino-ynamides via nucleophilic addition of lithiated ynamides to aryl imines are
      described. This work also features an aza-variant of a Meyer-Schuster
      rearrangement of gamma-amino-ynamides and the synthetic utility of gamma-amino
      ynamides in an intramolecular ketenimine-[2 + 2] cycloaddition.

PMID- 23976796
TI  - Studies toward welwitindolinones: formal syntheses of N-methylwelwitindolinone C
      isothiocyanate and related natural products.
AB  - The formal syntheses of N-methylwelwitindolinone C isothiocyanate (4) and several
      other welwitindolinones 5-8 were achieved by the independent synthesis of 79. The
      synthesis featured a Lewis acid-mediated coupling between a heteroaryl carbinol
      and bis-TMS enol ether, an intramolecular enolate arylation, and an unprecedented
      intramolecular allylic alkylation of a gamma-acyloxyenone.

PMID- 23976797
TI  - Template-induced macrocycle diversity through large ring-forming alkylations of
      tryptophan.
AB  - Macrocyclic peptidomimetics are valuable in research and serve as lead compounds
      in drug discovery efforts. New methods to prepare such structures are of
      considerable interest. In this pilot study, we show that an organic template
      harboring a latent cinnamyl cation participates in novel Friedel-Crafts
      macrocyclization reactions with tryptophan. Upon joining the template to Trp-Trp
      Tyr, a single operation efficiently generates eight unique macrocycles. Each has
      been isolated and thoroughly characterized. Product distribution as a function of
      Bronsted and/or Lewis acidic conditions was explored, and outcomes were compared
      to rearrangements induced within a corresponding tyrosine-linked cyclic ether.
      The solution structure of a new macrocyclic pyrroloindoline was solved using a
      combination of two-dimensional NMR methods and molecular mechanics simulations.
      Template-induced structural diversification of peptide sequences harboring
      aromatic residues has potential to create myriad macrocycles that target surfaces
      involved in protein-protein interactions.

PMID- 23976798
TI  - Condensation reactions of guanidines with bis-electrophiles: Formation of highly
      nitrogenous heterocycles.
AB  - 2-Amino-1,4-dihydropyrimidines were reacted with bis-electrophiles to produce
      novel fused bi-pyrimidine, pyrimido-aminotriazine, and pyrimido-sulfonamide
      scaffolds. In addition, a quinazoline library was constructed using a guanidine
      Atwal-Biginelli reaction with 1-(quinazolin-2-yl)guanidines. The product
      heterocycles have novel constitutions with high nitrogen atom counts and
      represent valuable additions to screening libraries for the discovery of new
      modulators of biological targets.

PMID- 23976799
TI  - The Relationship Between Obesity and Depression Among Adolescents.

PMID- 23976800
TI  - Community-level Effects of Individual and Peer Risk and Protective Factors on
      Adolescent Substance Use.
AB  - The association between community-aggregated levels of peer and individual risk
      and protective factors and prevalence of adolescent substance use was examined in
      repeated cross-sectional data among youth in 41 communities ranging in population
      from 1,578 to 106,221. The association between community levels of these peer and
      individual risk and protective factors in 2000 and substance use 2 years later
      was examined by using within-cohort analyses (e.g., sixth grade in 2000
      predicting eighth grade in 2002) and cross-cohort analyses (e.g., sixth grade in
      2000 predicting sixth grade in 2002). In both within- and across-cohort analyses,
      community-aggregated levels of peer and individual risk and protective factors
      predicted the prevalence of adolescent substance use 2 years later, suggesting
      that focusing on elevated peer and individual risk factors and depressed peer and
      individual protective factors at the community level to guide the selection of
      preventive interventions may be a viable strategy for community efforts to
      prevent adolescent substance use community wide.

PMID- 23976801
TI  - Cardiogenic mixing increases aerosol deposition in the human lung in the absence
      of gravity.
AB  - RATIONALE: Exposure to extraterrestrial dusts is an almost inevitable consequence
      of any proposed planetary exploration. Previous studies in humans showed reduced
      deposition in low-gravity compared with normal gravity (1G). However, the reduced
      sedimentation means that fewer particles deposit in the airways, increasing the
      number of particles transported to the lung periphery where they eventually
      deposit albeit at a smaller rate than in 1G. In this study, we determined the
      role that gravity and other mechanisms such as cardiogenic mixing play in
      peripheral lung deposition during breath holds. METHODS: Eight healthy subjects
      inhaled boluses of 0.5 MUm-diameter particles to penetration volumes (Vp) of 300
      and 1200ml that were followed by breath holds of up to 10 sec. Tests were
      performed in 1G and during short periods of microgravity (MUG) aboard the NASA
      Microgravity Research Aircraft. Aerosol deposition and dispersion were calculated
      from these data. RESULTS: Results show that, for both Vp, deposition in 1G was
      significantly higher than in MUG. In contrast, while dispersion was significantly
      higher in 1G compared to MUG at Vp=1200ml, there was no significant gravitational
      effect on dispersion at Vp=300ml. Finally, for each G level and Vp, deposition
      and dispersion significantly increased with increasing breath-hold time.
      CONCLUSION: The most important finding of this study is that, even in the absence
      of gravity, aerosol deposition in the lung periphery increased with increasing
      residence time. Because the particles used in this study were too large to be
      significantly affected by Brownian diffusion, the increase in deposition is
      likely due to cardiogenic motion effects.

PMID- 23976802
TI  - Insulin-like growth factor-1 receptor in mature osteoblasts is required for
      periosteal bone formation induced by reloading.
AB  - Skeletal loading and unloading has a pronounced impact on bone remodeling, a
      process also regulated by insulin-like growth factor 1 (IGF-1) signaling.
      Skeletal unloading leads to resistance to the anabolic effect of IGF-1, while
      reloading after unloading restores responsiveness to IGF-1. However, a direct
      study of the importance of IGF-1 signaling in the skeletal response to mechanical
      loading remains to be tested. In this study, we assessed the skeletal response of
      osteoblast-specific Igf-1 receptor deficient (Igf-1r-/- ) mice to unloading and
      reloading. The mice were hindlimb unloaded for 14 days and then reloaded for 16
      days. Igf-1r-/- mice displayed smaller cortical bone and diminished periosteal
      and endosteal bone formation at baseline. Periosteal and endosteal bone formation
      decreased with unloading in Igf-1r+/+ mice. However, the recovery of periosteal
      bone formation with reloading was completely inhibited in Igf-1r-/- mice,
      although reloading-induced endosteal bone formation was not hampered. These
      changes in bone formation resulted in the abolishment of the expected increase in
      total cross-sectional area with reloading in Igf-1r-/- mice compared to the
      control mice. These results suggest that the Igf-1r in mature osteoblasts has a
      critical role in periosteal bone formation in the skeletal response to mechanical
      loading.

PMID- 23976805
TI  - Efficient Robust Regression via Two-Stage Generalized Empirical Likelihood.
AB  - Large- and finite-sample efficiency and resistance to outliers are the key goals
      of robust statistics. Although often not simultaneously attainable, we develop
      and study a linear regression estimator that comes close. Efficiency obtains from
      the estimator's close connection to generalized empirical likelihood, and its
      favorable robustness properties are obtained by constraining the associated sum
      of (weighted) squared residuals. We prove maximum attainable finite-sample
      replacement breakdown point, and full asymptotic efficiency for normal errors.
      Simulation evidence shows that compared to existing robust regression estimators,
      the new estimator has relatively high efficiency for small sample sizes, and
      comparable outlier resistance. The estimator is further illustrated and compared
      to existing methods via application to a real data set with purported outliers.

PMID- 23976803
TI  - Prediction of trabecular bone qualitative properties using scanning quantitative
      ultrasound.
AB  - Microgravity induced bone loss represents a critical health problem in
      astronauts, particularly occurred in weight-supporting skeleton, which leads to
      osteopenia and increase of fracture risk. Lack of suitable evaluation modality
      makes it difficult for monitoring skeletal status in long term space mission and
      increases potential risk of complication. Such disuse osteopenia and osteoporosis
      compromise trabecular bone density, and architectural and mechanical properties.
      While X-ray based imaging would not be practical in space, quantitative
      ultrasound may provide advantages to characterize bone density and strength
      through wave propagation in complex trabecular structure. This study used a
      scanning confocal acoustic diagnostic and navigation system (SCAN) to evaluate
      trabecular bone quality in 60 cubic trabecular samples harvested from adult
      sheep. Ultrasound image based SCAN measurements in structural and strength
      properties were validated by MUCT and compressive mechanical testing. This result
      indicated a moderately strong negative correlations observed between broadband
      ultrasonic attenuation (BUA) and MUCT-determined bone volume fraction (BV/TV,
      R2=0.53). Strong correlations were observed between ultrasound velocity (UV) and
      bone's mechanical strength and structural parameters, i.e., bulk Young's modulus
      (R2=0.67) and BV/TV (R2=0.85). The predictions for bone density and mechanical
      strength were significantly improved by using a linear combination of both BUA
      and UV, yielding R2=0.92 for BV/TV and R2=0.71 for bulk Young's modulus. These
      results imply that quantitative ultrasound can characterize trabecular structural
      and mechanical properties through measurements of particular ultrasound
      parameters, and potentially provide an excellent estimation for bone's structural
      integrity.

PMID- 23976804
TI  - Increasing the Number of Unloading/Reambulation Cycles does not Adversely Impact
      Body Composition and Lumbar Bone Mineral Density but Reduces Tissue Sensitivity.
AB  - A single exposure to hindlimb unloading leads to changes in body mass, body
      composition and bone, but the consequences of multiple exposures are not yet
      understood. Within a 18wk period, adult C57BL/6 male mice were exposed to one (1x
      HLU), two (2x-HLU) or three (3x-HLU) cycles of 2 wk of hindlimb unloading (HLU)
      followed by 4 wk of reambulation (RA), or served as ambulatory age-matched
      controls. In vivo uCT longitudinally tracked changes in abdominal adipose and
      lean tissues, lumbar vertebral apparent volumetric bone mineral density (vBMD)
      and upper hindlimb muscle cross-sectional area before and after the final HLU and
      RA cycle. Significant decreases in total adipose tissue and vertebral vBMD were
      observed such that all unloaded animals reached similar values after the final
      unloading cycle. However, the magnitude of these losses diminished in mice
      undergoing their 2nd or 3rd HLU cycle. Irrespective of the number of HLU/RA
      cycles, total adipose tissue and vertebral vBMD recovered and were no different
      from age-matched controls after the final RA period. In contrast, upper hindlimb
      muscle cross-sectional area was significantly lower than controls in all unloaded
      groups after the final RA period. These results suggest that tissues in the
      abdominal region are more resilient to multiple bouts of unloading and more
      amenable to recovery during reambulation than the peripheral musculoskeletal
      system.

PMID- 23976806
TI  - The Role of Neighborhood Safety in Recovery from Mobility Limitations: Findings
      from a National Sample of Older Americans (1996-2008).
AB  - Prior research has documented a link between perceived neighborhood safety and
      functional limitations including incident mobility limitation, yet no research
      has explored the association between perceived neighborhood safety and recovery
      from functional limitations. This study investigates whether perceived
      neighborhood safety independently predicts recovery. Using longitudinal data from
      the Health and Retirement Study (HRS) (1996-2008), discrete-time event history
      models with multiple competing events were estimated using multinomial logistic
      regression. Robust standard errors were used to adjust for clustering. In the
      unadjusted model, the odds ratio for recovery from mobility limitations was 1.22
      (CI: 1.17, 1.27) for respondents reporting greater neighborhood safety, while, in
      the fully adjusted model, the odds ratio was 1.11 (CI: 1.05, 1.17). Even after
      controlling for sociodemographic characteristics and numerous health risk
      factors, perceived neighborhood safety was a robust predictor of mobility
      limitation recovery. This research provides further evidence that environmental
      factors shape functional health outcomes including recovery.

PMID- 23976807
TI  - A Pure L1-norm Principal Component Analysis.
AB  - The L1 norm has been applied in numerous variations of principal component
      analysis (PCA). L1-norm PCA is an attractive alternative to traditional L2-based
      PCA because it can impart robustness in the presence of outliers and is indicated
      for models where standard Gaussian assumptions about the noise may not apply. Of
      all the previously-proposed PCA schemes that recast PCA as an optimization
      problem involving the L1 norm, none provide globally optimal solutions in
      polynomial time. This paper proposes an L1-norm PCA procedure based on the
      efficient calculation of the optimal solution of the L1-norm best-fit hyperplane
      problem. We present a procedure called L1-PCA* based on the application of this
      idea that fits data to subspaces of successively smaller dimension. The procedure
      is implemented and tested on a diverse problem suite. Our tests show that L1-PCA*
      is the indicated procedure in the presence of unbalanced outlier contamination.

PMID- 23976808
TI  - Optimized Synthesis of Salicylate-based Poly(anhydride-esters).
AB  - The synthesis of a salicylate-based poly(anhydride-ester) was optimized to
      improve the overall efficiency and quality of the polymer. First, a new approach
      for the preparation of the polymer precursor minimizes the overall number of
      synthetic steps and increases the overall yield. Second, the melt-polymerization
      apparatus was modified to include dynamic mixing, which yields polymer with
      increased molecular weights on both the milligram and gram scale.

PMID- 23976809
TI  - Implementing a Case Management Initiative in High-Need Schools.
AB  - States continue to experiment with ways of improving health and human service use
      by people with complex needs. Such efforts have often sought to increase
      individual and family control over services as well as to enhance coordination
      among providers. Paths to achieving these goals are not well understood. This
      study draws on two previously distinct conceptual frameworks to examine how 71
      public schools implemented a team approach to increasing family and agency
      engagement for children at risk. Results from longitudinal data fit the core
      components expected to affect implementation and also indicated sustainability,
      but in ways distinctive to the initiative's public school settings.
      Accountability to the state appeared to be a major catalyst, yet in some respects
      also constrained local agencies from participating as intended. School inertia
      may have both undermined the program through some evaluation practices and gaps
      in administrative support, and supported integration into organizational routines
      and successful experimentation over time in increasing caregiver involvement.
      Family hesitation about sharing information with multiple agencies may also help
      explain why the goal of seamless coordination remains elusive.

PMID- 23976810
TI  - Individual differences in positivity offset and negativity bias: Gender-specific
      associations with two serotonin receptor genes.
AB  - Individual differences in the evaluation of affective stimuli, such as the
      positivity offset and negativity bias may have a biological basis. We tested
      whether two SNPs (HTR2A; 102T>C and HTR1A; 1019C>G) related to serotonin receptor
      function, a biological pathway associated with affective regulation, were
      differentially related to positivity offset and negativity bias for males and
      females. Participants were 109 cigarette smokers who rated a series of affective
      stimuli to assess reactions to positive and negative pictures. Gender * genotype
      interactions were found for both SNPs. Males with the 102T allele showed a
      greater positivity offset than males with the 102C allele. For females, in
      contrast, the 1019C allele was associated with a greater positivity offset than
      the 1019G allele, whereas the 102T allele was associated with a greater
      negativity bias than the 102C allele. Identifying how gender differences may
      moderate the effect of serotonin receptor genes on affective information
      processing may provide insight into their role in guiding behavior and regulating
      affect.

PMID- 23976811
TI  - Parental support during young adulthood: Why does assistance decline with age?
AB  - Previous research has found that financial transfers from parents to young adult
      children decline as children age and that age is one of the strongest predictors
      of support. Using data collected from young adults (ages 18 to 34) and their
      parents (ages 40 to 60; N=536 parent-child dyads), we explore the possibility
      that the relationship between age and financial support is mediated by offspring
      needs, acquisition of adult roles, or geographical and emotional closeness. We
      find that age-related declines in offspring's needs help to explain why financial
      support falls with age. However, offspring age remains a robust predictor of
      financial support after controlling for a wide range of factors, suggesting that
      age norms condition support from parents to offspring.

PMID- 23976812
TI  - Optimal Design of Honeycomb Material Used to Mitigate Head Impact.
AB  - This paper presents a study of the impact resistance of honeycomb structure with
      the purpose to mitigate impact forces. The objective is to aid in the choice of
      optimal parameters to minimize the thickness of the honeycomb structure while
      providing adequate protection to prevent injury due to head impact. Studies are
      presented using explicit finite element analysis representing the case of an
      unprotected drop of a rigid impactor onto a simulated floor consisting of vinyl
      composition tile and concrete. Analysis of honeycomb material to reduce resulting
      accelerations is also presented where parameters such as honeycomb material
      modulus, wall thickness, cell geometry and structure depth are compared to the
      unprotected case. A simplified analysis technique using a genetic algorithm is
      presented to demonstrate the use of this method to select a minimum honeycomb
      depth to achieve a desired acceleration level at a given level of input energy.
      It is important to select a minimum material depth in that smaller dimensions
      lead toward more aesthetic design that increase the likelihood of that the device
      is used.

PMID- 23976813
TI  - A tutorial on aphasia test development in any language: Key substantive and
      psychometric considerations.
AB  - BACKGROUND: There are a limited number of aphasia language tests in the majority
      of the world's commonly spoken languages. Furthermore, few aphasia tests in
      languages other than English have been standardized and normed, and few have
      supportive psychometric data pertaining to reliability and validity. The lack of
      standardized assessment tools across many of the world's languages poses serious
      challenges to clinical practice and research in aphasia. AIMS: The current review
      addresses this lack of assessment tools by providing conceptual and statistical
      guidance for the development of aphasia assessment tools and establishment of
      their psychometric properties. MAIN CONTRIBUTION: A list of aphasia tests in the
      20 most widely spoken languages is included. The pitfalls of translating an
      existing test into a new language versus creating a new test are outlined.
      Factors to consider in determining test content are discussed. Further, a
      description of test items corresponding to different language functions is
      provided, with special emphasis on implementing important controls in test
      design. Next, a broad review of principal psychometric properties relevant to
      aphasia tests is presented, with specific statistical guidance for establishing
      psychometric properties of standardized assessment tools. CONCLUSIONS: This
      article may be used to help guide future work on developing, standardizing and
      validating aphasia language tests. The considerations discussed are also
      applicable to the development of standardized tests of other cognitive functions.

PMID- 23976814
TI  - Trait Mindfulness Predicts Attentional and Autonomic Regulation of Alcohol Cue
      Reactivity.
AB  - BACKGROUND: The trait of mindfulness varies among meditation-naive individuals
      and is associated with attentional and autonomic regulation, two neurocognitive
      functions that become impaired in addiction. It was hypothesized that alcohol
      dependent inpatients with comparatively high levels of trait mindfulness would
      exhibit significant autonomic recovery from stress-primed alcohol cues mediated
      by greater attentional disengagement from such cues. METHODS: 58 alcohol
      dependent inpatients participated in affect-modulated psychophysiological cue
      reactivity protocol and a spatial cueing task designed to assess alcohol
      attentional bias (AB). Associations between trait mindfulness, alcohol AB, and an
      index of autonomic activity, high-frequency heart rate variability (HFHRV), were
      examined via multivariate path analysis. RESULTS: Higher trait mindfulness was
      significantly associated with less difficulty resisting the urge to drink and
      greater HFHRV recovery from stress-primed alcohol cues. After statistically
      controlling for the correlation of mindfulness and perceived difficulty resisting
      drinking urges, the association between mindfulness and HFHRV recovery was
      partially mediated by attentional disengagement from alcohol cues (model R2 =
      .30). DISCUSSION: Alcohol dependent inpatients higher in mindfulness are better
      able to disengage attention from alcohol cues, which in turn predicts the degree
      of HFHRV recovery from such cues. Trait mindfulness may index cognitive control
      over appetitive responses reflected in superior attentional and autonomic
      regulation of stress-primed alcohol cue-reactivity.

PMID- 23976815
TI  - Decomposition of a Mixed-Valence [2Fe-2S] Cluster to Linear Tetra-Ferric and
      Ferrous Clusters.
AB  - Despite the ease of preparing di-ferric [2Fe-2S] clusters, preparing stable mixed
      valence analogues remains a challenge, as these clusters have limited thermal
      stability. Herein we identify two decomposition products of the mixed-valence
      thiosalicylate-ligated [2Fe-2S] cluster, [Fe2S2(SArCOO)2]3- ((SArCOO)2- =
      thiosalicylate).

PMID- 23976817
TI  - Raising Children in a Violent Context: An intersectionality approach to
      understanding parents' experiences in Ciudad Juarez.
AB  - Children and parents' daily lives are rarely highlighted in coverage of drug
      wars. Using 16 interviews with parents in the Mexican border city of Juarez in
      2010, we examine how drug violence impacts families with a focus on intersections
      of gender and social class. Related to mobility (the first emergent theme),
      fathers had increased mobility as compared to mothers, which caused different
      stresses. Material hardships heightened mothers' isolation within the home, and
      mothers more often had to enforce children's mobility restrictions, which
      children resisted. Related to employment (the second emergent theme), fathers
      took on dangerous jobs to provide for the family while mothers had fewer options
      for informal employment due to violence. In sum, men and women faced different
      challenges, which were intensified due to class-based material disadvantages.
      Conformity with traditional gender expectations for behavior was common for men
      and women, illustrating the normalization of gender inequality within this
      context.

PMID- 23976816
TI  - Kinetics of CO Recombination to the Heme in Geobacillus Stearothermophilus Nitric
      Oxide Synthase.
AB  - We report the kinetics of CO rebinding to the heme in His134Ser, Ile223Val and
      His134Ser/Ile223Ser mutants of Geobacillus stearothermophilus nitric oxide
      synthase (gsNOS). The amplitudes of the two observed kinetics phases, which are
      insensitive to CO concentration, depend on enzyme concentration. We suggest that
      two forms of gsNOS are in equilibrium under the conditions employed (6.1-27 uM
      gsNOS with 20 or 100% CO atmosphere). The kinetics of CO rebinding to the heme do
      not depend on the identity of the NO-gate residues at positions 134 and 223.

PMID- 23976818
TI  - Access to Housing in Urban China.
AB  - Like income inequality, housing inequality in urban China is strongly affected by
      state policies that give preferential treatment to insiders. In this case, the
      key policies are related to their residence status, which involves not only their
      migration history but also their legal position. Using data from the Chinese
      census of 2000 for eight large cities, this study shows how residence status
      affects access to various pathways to housing. In addition to the well-known
      marginal housing situation of the recent 'floating population', it documents
      surprising advantages for migrants with urban registration status and persistent
      disadvantages for rural migrants regardless of how long they have lived in the
      city.

PMID- 23976819
TI  - Theoriser la violence en Ameerique: Retour sur trente ans d'ethnographie.
AB  - PHILIPPE BOURGOIS THEORIZING VIOLENCE IN THE AMERICAS A THIRTY-YEAR ETHNOGRAPHIC
      RETROSPECTIVE: This thirty year retrospective analysis of violence at my
      fieldwork sites in the Americas (Nicaragua, El Salvador, Costa Rica, Panama, USA)
      explores the importance and difficulty of recognizing the continuities of
      violence across historical eras as an ethnographer. Expanding on the continuum of
      violence concept, I propose the utility of identifying the mutually reinforcing
      interface of three overlapping categories of invisible violence: structural,
      symbolic and normalized. If theory is meant to help us see more, then theorizing
      violence through a continuum of categories of invisibility is useful because it
      contravenes the political effects of the contemporary hyper-visibility of
      interpersonal and petty criminal street violence. The increasing global reach of
      a punitive version of corporate neoliberalism over the past two decades has
      lumpenized large sectors of the urban and rural poor. Recognizing the links
      between categories of invisible violence in this globalized context of social
      inequality explains the demobilization of class-based demands for economic
      redistribution and populist support for physically repressive forms of
      governmentality that punish the poor deemed unworthy.

PMID- 23976820
TI  - Information use environments of African-American dementia caregivers over the
      course of cognitive-behavioral therapy for depression.

PMID- 23976821
TI  - Drought sensitivity of three co-occurring conifers within a dry inner Alpine
      environment.
AB  - We applied dendroclimatological techniques to determine long-term stationarity of
      climate-growth relationships and recent growth trends of three widespread
      coniferous tree species of the central Austrian Alps, which grow intermixed at
      dry-mesic sites within a dry inner Alpine environment (750 m asl). Time series of
      annual increments were developed from > 120 mature trees of Picea abies, Larix
      decidua and Pinus sylvestris. Calculation of response functions for the period
      1911 - 2009 revealed significant differences among species in response to climate
      variables. While precipitation in May - June favoured radial growth of Picea
      abies and Larix decidua, Pinus sylvestris growth mainly depended on April - May
      precipitation. P. abies growth was most sensitive to May - June temperature
      (inverse relationship). Moving response function coefficients indicated
      increasing drought sensitivity of all species in recent decades, which is related
      to a decline in soil moisture availability due to increasing stand density and
      tree size and higher evapotranspiration rates in a warmer climate. While recent
      trend in basal area increment (BAI) of L. decidua distinctly declined implying
      high vulnerability to drought stress, moderately shade-tolerant P. abies showed
      steadily increasing BAI and quite constant BAI was maintained in drought adapted
      P. sylvestris, although at lowest level of all species. We conclude that
      synergistic effects of stand dynamics and climate warming increased drought
      sensitivity, which changed competitive strength of co-occurring conifers due to
      differences in inherent adaptive capacity.

PMID- 23976822
TI  - Anti-CRLF2 Antibody-Armored Biodegradable Nanoparticles for Childhood B-ALL.
AB  - B-precursor acute lymphoblastic leukemia (B-ALL) lymphoblast (blast)
      internalization of anti-cytokine receptor-like factor 2 (CRLF2) antibody-armored
      biodegradable nanoparticles (AbBNPs) are investigated. First, AbBNPsaere
      synthesized by adsorbing anti-CRLF2 antibodies to poly(D,L-lactide- co 
      glycolide) (PLGA) nanoparticles of various sizes and antibody surface density
      (Ab/BNP) ratios. Second, AbBNPs are incubated with CRLF2-overexpressing (CRLF2+)
      or control blasts. Third, internalization of AbBNPs by blasts is evaluated by
      multicolor flow cytometry as a function of receptor expression, AbBNP size, and
      Ab/BNP ratio. Results from these experiments are con-firmed by electron
      microscopy, fluorescence microscopy, and Western blotting. The optimal size and
      Ab/BNP for internalization of AbBNPs by CRLF2+ blasts is 50 nm with 10 Ab/BNP and
      100 nm with 25 Ab/BNP. These studies show that internalization of AbBNPs in
      childhood B-ALL blasts is AbBNP size-and Ab/BNP ratio-dependent. All AbBNP
      combinations are non-cytotoxic. It is also shown that CD47 is very slightly up
      regulated by blasts exposed to AbBNPs. CD47 is "the marker of self" overexpressed
      by blasts to escape phagocytosis, or "cellular devouring", by beneficial
      macrophages. The results indicate that precise engineering of AbBNPs by size and
      Ab/BNP ratio may improve the internalization and selectivity of future
      biodegradable nanoparticles for the treatment of leukemia patients, including
      drug-resistant minority children and Down's syndrome patients with CRLF2+B-ALL.

PMID- 23976823
TI  - A COGNITIVE PERSPECTIVE ON AGGRESSIVE MIMICRY.
AB  - We use the term 'aggressive mimic' for predators that communicate with their prey
      by making signals to indirectly manipulate prey behaviour. For understanding why
      the aggressive mimic's signals work, it is important to appreciate that these
      signals interface with the prey's perceptual system, and that the aggressive
      mimic can be envisaged as playing mind games with its prey. Examples of
      aggressive mimicry vary from instances in which specifying a model is straight
      forward to instances where a concise characterisation of the model is difficult.
      However, the less straightforward examples of aggressive mimicry may be the more
      interesting examples in the context of animal cognition. In particular, there are
      spiders that prey on other spiders by entering their prey's web and making
      signals. Web invasion brings about especially intimate contact with their prey's
      perceptual system because the prey spider's web is an important component of the
      prey spider's sensory apparatus. For the web-invading spider, often there is also
      a large element of risk when practising aggressive mimicry because the intended
      prey is also a potential predator. This element of risk, combined with
      exceptionally intimate interfacing with prey perceptual systems, may have
      favoured the web-invading aggressive mimic's strategy becoming strikingly
      cognitive in character. Yet a high level of flexibility may be widespread among
      aggressive mimics in general and, on the whole, we propose that research on
      aggressive mimicry holds exceptional potential for advancing our understanding of
      animal cognition.

PMID- 23976824
TI  - Combinatorial screening of chemically defined human mesenchymal stem cell culture
      substrates.
AB  - Self-assembled monolayers (SAMs) of alkanethiolates on gold are chemically
      defined substrates that can be used to evaluate the effects of an immobilized
      biomolecule. However, the types of biomolecules that can influence stem cell
      behavior are numerous and inter-related, and efficient experimental formats are a
      critical need. Here we employed a SAM array technology to investigate the effects
      of multiple, distinct peptides and peptide combinations on human mesenchymal stem
      cell (hMSC) behavior. Specifically, we characterized the conjugation of peptide
      mixtures to SAM arrays and then investigated the combined effects of a bone
      morphogenic protein receptor-binding peptide (BR-BP), a heparin proteoglycan
      binding peptide (HPG-BP), and varied densities of the integrin-binding ligand Gly
      Arg-Gly-Asp-Ser-Pro (GRGDSP) on hMSC surface coverage and alkaline phosphatase
      activity. Results indicate that an amine reactive fluorescent probe can be used
      to characterize peptide composition after immobilization in SAM array spots.
      Furthermore, hMSC response to BR-BP and HPG-BP is dependent on GRGDSP density and
      at day 7, hMSC alkaline phosphatase expression is highly dependent on GRGDSP
      density. Taken together, we demonstrate how a SAM array approach can be used to
      probe the combinatorial effects of multiple peptides and motivate further
      investigations into potential synergies between cell adhesion and other bioactive
      peptides.

PMID- 23976825
TI  - Computer aided screening of Accacia nilotica phytochemicals against HCV NS3/4a.
AB  - BACKGROUND: HCV has become a leading cause of liver cirrhosis and hepatocellular
      carcinoma and is a major health concern worldwide. To date, there is no vaccine
      available in the market to tackle this disease, therefore there is a strong need
      to develop antiviral compounds that can target all genotypes of HCV with the same
      efficiency. Medicinal plants have low cost and are less toxic therefore, extracts
      of medicinal plants can serve as important antiviral agents against HCV. This
      study was designed to screen phytochemicals of Accacia nilotica to find a potent
      drug candidate that can inhibit HCV infection effectively. RESULTS: Docking of
      NS3/4A protease and Flavonoids of Accacia nilotica revealed that most of the
      flavonoids bound deeply with the active site of NS3/4A protease. Compound 01
      showed a high ranking on docking score. All other compounds also showed reliable
      docking scores and had interactions with the binding cavity of NS3/4A protease,
      suggesting them as a potent drug candidate to block HCV replication. CONCLUSION:
      To recognize binding interactions of Accacia nilotica phytochemicals with NS3/4A
      protease, molecular docking was performed to find potential inhibitor against
      NS3/4A protease of HCV. After post docking analysis, important interactions were
      found between active compounds and active site of NS3/4A protease. It can be
      concluded from the study that phytochemicals of Accacia nilotica may serve as a
      potential drug candidate with relatively simple structural changes against HCV
      NS3/4A protease.

PMID- 23976827
TI  - Improving communication skill training in patient centered medical practice for
      enhancing rational use of laboratory tests: The core of bioinformation for
      leveraging stakeholder engagement in regulatory science.
AB  - Requests for laboratory tests are among the most relevant additional tools used
      by physicians as part of patient's health problemsolving. However, the
      overestimation of complementary investigation may be linked to less reflective
      medical practice as a consequence of a poor physician-patient communication, and
      may impair patient-centered care. This scenario is likely to result from reduced
      consultation time, and a clinical model focused on the disease. We propose a new
      medical intervention program that specifically targets improving the patient
      centered communication of laboratory tests results, the core of bioinformation in
      health care. Expectations are that medical students training in communication
      skills significantly improve physicians-patient relationship, reduce
      inappropriate use of laboratorial tests, and raise stakeholder engagement. 

PMID- 23976826
TI  - Computational Analysis of N-acetyl transferase in Tribolium castaneum.
AB  - N-acetyl transferase (NAT) is responsible to catalyze the transfer of acetyl
      groups to arylamines from acetyl-CoA. Aralkylamine Nacetyl transferase (AANAT),
      which belongs to GCN5-related N-acetyl transferase member, is a globular 23-kDa
      cytosolic protein that forms a reversible regulatory complex with 14-3-3
      proteins, AANAT regulates the daily cycle of melatonin biosynthesis in mammals,
      making it an attractive target for therapeutic control of abnormal melatonin
      production in mood and sleep disorders. There is no evidence available regarding
      alpha and beta subunits, active site and their ASA value in Dopamine N-acetyl
      transferase. Therefore, we describe the development of Dopamine N-acetyl
      transferase model in Tribolium castaneum. We further document the predicted
      active sites in the structural model with solvent exposed ASA residues. During
      this study, the model was built by CPH program and validated through PROCHECK,
      Verify 3D, ERRAT and ProSA for reliability. The active sites were predicted in
      the model with further ASA analysis of active site residues. The discussed
      information thus provides insight to the predicted active site and ASA values of
      Dopamine N-acetyl transferase model in Tribolium castaneum. 

PMID- 23976828
TI  - Docking studies of Vitamin C, Vitamin E, Damnacanthal and Scopoletin with human
      lens gamma D-crystalline.
AB  - Vitamin C, Vitamin E, scopoletin and damnacanthal are the major constituents of
      Noni (Morinda citrifolia). These compounds are known to have good medicinal
      properties and they are known to act as antioxidants. Loss of vision in elderly
      is due to opaqueness of the lens proteins such as gamma-D-crystallin during
      oxidative stress conditions. Therefore, it is of importance to find the potential
      interaction of Vitamin C, Vitamin E, Scopoletin and Damnacanthal with the lens
      protein gamma-D-crystallin. Hence, their physical binding to gamma-D crystallin
      (PDB ID: 2G98) was evaluated using molecular and structural docking procedures.
      Results show the potential binding of all the above anti-oxidants to gamma-D
      crystalline with equal affinity. Thus, the role of cumulative anti-oxidant effect
      in Noni fruit juice through their potential yet predicted interaction with the
      lens protein gamma-D-crystallin is implied for cataract treatment. 

PMID- 23976829
TI  - Three dimensional (3D) structure prediction and substrate-protein interaction
      study of the chitin binding protein CBP24 from B. thuringiensis.
AB  - Bacillus thuringiensis is an insecticidal bacterium whose chitinolytic system has
      been exploited to improve insect resistance in crops. In the present study, we
      studied the CBP24 from B. thuringiensis using homology modeling and molecular
      docking. The primary and secondary structure analyses showed CBP24 is a
      positively charged protein and contains single domain that belongs to family
      CBM33. The 3D model after refinement was used to explore the chitin binding
      characteristics of CBP24 using AUTODOCK. The docking analyses have shown that the
      surface exposed hydrophilic amino acid residues Thr-103, Lys-112 and Ser-162
      interact with substrate through H-bonding. While, the amino acids resides Glu-39,
      Tyr-46, Ser-104 and Asn-109 were shown to have polar interactions with the
      substrate. The binding energy values evaluation of docking depicts a stable
      intermolecular conformation of the docked complex. The functional
      characterization of the CBP24 will elucidate the substrate-interaction pathway of
      the protein in specific and the carbohydrate binding proteins in general leading
      towards the exploration and exploitation of the prokaryotic substrate utilization
      pathways. 

PMID- 23976830
TI  - An insight into the lignin peroxidase of Macrophomina phaseolina.
AB  - Macrophomina phaseolina is one of the deadliest necrotrophic fungal pathogens
      that infect more than 500 plant species including major food, fiber, and oil
      crops all throughout the globe. It secretes a cocktail of ligninolytic enzymes
      along with other hydrolytic enzymes for degrading the woody lignocellulosic plant
      cell wall and penetrating into the host tissue. Among them, lignin peroxidase has
      been reported only in Phanerochaete chrysosporium so far. But interestingly, a
      recent study has revealed a second occurrence of lignin peroxidase in M.
      phaseolina. However, lignin peroxidases are of much significance
      biotechnologically because of their potential applications in bio-remedial waste
      treatment and in catalyzing difficult chemical transformations. Besides, this
      enzyme also possesses agricultural and environmental importance on account of
      their role in lignin biodegradation. In the present work, different properties of
      the lignin peroxidase of M. phaseolina along with predicting the 3-D structure
      and its active sites were investigated by the use of various computational tools.
      The data from this study will pave the way for more detailed exploration of this
      enzyme in wet lab and thereby facilitating the strategies to be designed against
      such deadly weapons of Macrophomina phaseolina. Furthermore, the insight of such
      a ligninolytic enzyme will contribute to the assessment of its potentiality as a
      bioremediation tool. 

PMID- 23976831
TI  - Possible utilization of -1 Ribosomal frame shifting in the expression of a human
      SEMA6C isoform.
AB  - We have used bioinformatics approaches to identify a potential case of -1
      ribosomal frame shifting in the mRNAs of the three variants of human SEMA6C
      protein. The mRNAs contain a heptanucleotide slippery sequence followed by a
      compact H-type pseudoknot. Unlike -1 frameshifting signals in viral or viral-like
      mRNAs, the slippery sequence and downstream pseudoknot in SEMA6C mRNAs locate 423
      nucleotides (encoding 141 amino acids) upstream of the stop codon. The potential 
      1 frameshifting event would produce a polypeptide of 238 residues encoded by the 
      1 reading frames. Sequence similarity searches using BLAST indicate that ~90% of
      the 238 residues match actual protein sequences annotated as SEMA6C proteins in
      the database. We propose that the mRNAs of human SEMA6C utilize a pseudoknot
      dependent -1 ribosomal frameshifting mechanism to express novel SEMA6C isoforms. 

PMID- 23976832
TI  - Analysis of gene expression on ngn3 gene signaling pathway in endocrine
      pancreatic cancer.
AB  - In order to define the undifferentiated transcriptional factors present in
      neurogenesis of pancreatic beta-islet cells, we studied the effect of Pdx1 in
      embryonic stem cell derived endocrine lineage. There are undifferentiated
      transcriptional progenitors Pdx1+/Ptf1a+/Cpa1+ tracking the growth of acini,
      ducts, alpha and beta-islet cells. The upregulated transcriptional factors Pdx1
      and ngn3 specify consequences of cell cycle regulation in early gut endocrine
      cells. The undifferentiated transcriptional factors basic helix loop helix (bHLH)
      protein regulate Ptf1a+/Cpa1+ in acini, ducts and it also regulate ngn3 to
      decrease expression of insulin and other pancreas secretions. The Pdx1+ and other
      unknown gene mutations show abnormal growth of neurogenesis in endocrine
      lineages. Using microarray based gene expression analysis to determine
      undifferential gene ontology in tissue specific gene regulation and disease
      progression that common in both metabolic and biological signaling pathways. The
      data expression profiles of ngn3 of wild- type pancreatic islet and islet derived
      tumor stem cells provide information on endocrine specific ngn3 genes. Therefore,
      3755 genes were significantly regulated by Ngn3 induced pancreatic islet cell
      development. Moreover 317 upregulated and 175 downregulated, 757 genes deemed as
      undifferential expressions in endocrine cell. Furthermore to predict signaling
      pathways that associates with diabetes is highlighted. 

PMID- 23976833
TI  - HOMO: A novel script for data mining of microarrays.
AB  - HOMO.pl is a perl script that allows extracting important registers from an
      extensive data table or microarrays results. It is very useful in data mining for
      microarrays analysis. HOMO works as a homogenizer that converts the initial data
      table into more specific and manageable data according to a list of important
      genes or terms. This is very useful when a pathway, a condition, or a GO-Term is
      studied. The HOMO script has two inputs and one principal output. A table with
      the microarray data results is used as an input and a list of genes or important
      terms is used as a second input. The output is an adjusted table from the
      microarray results that contains only the genes included in the input list.
      HOMO's principal goal is to simplify the subsequent analyses to the microarray
      data. AVAILABILITY: HOMO.pl and a suite of example files are available by
      electronic mail request.

PMID- 23976834
TI  - Sliding Box Docking: a new stand-alone tool for managing docking-based virtual
      screening along the DNA helix axis.
AB  - Sliding Box Docking is a program that manages simulations of ligand docking at
      different defined positions of a three-dimensional DNA structure. The procedure
      is similar to inverse docking, which is a method that performs docking
      simulations of a single ligand in the active sites of different targets. Sliding
      Box Docking manages docking simulations of one ligand into a box that slides
      along the DNA helix axis in regular steps. For each box position a score is
      calculated using the separate Autodock Vina software, and the results are
      automatically plotted. The evaluation of ligand interaction at different DNA
      locations can highlight the specificity of ligands for different DNA- sequences.
      When assessing the affinity between ligans AT base pairs, results for docking
      simulations with a test set that included berenil, distamycin, hoechst 33258, and
      netropsin were as expected, agreeing well with affinities previously described in
      the literature. AVAILABILITY: Binaries are freely available at
      https://sourceforge.net/projects/slidingboxdocki.

PMID- 23976835
TI  - Quantitative Proteomics Identifies Activation of Hallmark Pathways of Cancer in
      Patient Melanoma.
AB  - Molecular pathways regulating melanoma initiation and progression are potential
      targets of therapeutic development for this aggressive cancer. Identification and
      molecular analysis of these pathways in patients has been primarily restricted to
      targeted studies on individual proteins. Here, we report the most comprehensive
      analysis of formalin-fixed paraffin-embedded human melanoma tissues using
      quantitative proteomics. From 61 patient samples, we identified 171 proteins
      varying in abundance among benign nevi, primary melanoma, and metastatic
      melanoma. Seventy-three percent of these proteins were validated by
      immunohistochemistry staining of malignant melanoma tissues from the Human
      Protein Atlas database. Our results reveal that molecular pathways involved with
      tumor cell proliferation, motility, and apoptosis are mis-regulated in melanoma.
      These data provide the most comprehensive proteome resource on patient melanoma
      and reveal insight into the molecular mechanisms driving melanoma progression.

PMID- 23976836
TI  - Testing independent censoring for longitudinal data.
AB  - A common problem associated with longitudinal studies is the dropouts of subjects
      or censoring before the end of follow-up. In most existing methods, it is assumed
      that censoring is noninformative about missed responses. This assumption is
      crucial to the validity of many statistical procedures. We develop some
      nonparametric hypothesis testing procedures to test for independent censoring in
      the absence/presence of covariates. The test statistics are constructed by
      contrasting two estimators of the conditional mean of cumulative responses for
      each stratum of covariate space from sample subsets with different patterns of
      censoring. Our method does not require the modelling of longitudinal response
      processes, therefore is robust to model misspecifications. A diagnostic plot
      procedure is also developed that can be used to identify dependent censoring to
      certain covariate strata. The finite sample performances of the tests are
      investigated through extensive simulation studies. The potential of our methods
      is demonstrated through the application of the tests to a chronic granulomatous
      disease study.

PMID- 23976837
TI  - Exposure to Parental Cigarette Smoking and Child Problem Behaviors: A
      Longitudinal Study.
AB  - This study examined exposure to environmental tobacco smoke (ETS). A major public
      health problem, ETS has been found to be associated with an increased risk of
      adverse health effects in children. This study utilizes data from a community
      based, longitudinal investigation examining the relation between children's
      exposure to ETS and later internalizing symptoms and externalizing behaviors.
      Interviews were administered to a representative community sample of participants
      from two New York State counties in 1983, with subsequent interviews in 1985
      1986, 1992, 1997, and 2002-2003 (when the participants' mean age was 32). Data
      was collected on various personality and behavioral characteristics of the
      participants, and on internalizing symptoms and externalizing behaviors
      demonstrated by their children. Results indicated that children's exposure to ETS
      was associated with an increased risk for both internalizing symptoms and
      externalizing behaviors. This relationship was maintained despite control on a
      number of parental psychosocial risk factors (e.g., demographic variables,
      personality and behavioral attributes) that have been found to be associated with
      both parental cigarette smoking and behavior problems among children. These data,
      which indicate an association between exposure to ETS and internalizing symptoms
      and externalizing behaviors among children, support public health policies to
      further restrict children's exposure to ETS.

PMID- 23976838
TI  - FIB Fabrication of Metallic Nanostructures on End-Faces of Optical Fibers for
      Chemical Sensing Applications.

PMID- 23976839
TI  - Multi-technique Characterization of Adsorbed Peptide and Protein Orientation:
      LK310 and Protein G B1.
AB  - The ability to orient biologically active proteins on surfaces is a major
      challenge in the design, construction, and successful deployment of many medical
      technologies. As methods to orient biomolecules are developed, it is also
      essential to develop techniques that can an accurately determine the orientation
      and structure of these materials. In this study, two model protein and peptide
      systems are presented to highlight the strengths of three surface analysis
      techniques for characterizing protein films: time-of-flight secondary ion mass
      spectrometry (ToF-SIMS), sum-frequency generation (SFG) vibrational spectroscopy,
      and near-edge x-ray absorption fine structure (NEXAFS) spectroscopy. First, the
      orientation of Protein G B1, a rigid 6 kDa domain covalently attached to a
      maleimide-functionalized self-assembled monolayer, was examined using ToF-SIMS.
      Although the thickness of the Protein G layer was similar to the ToF-SIMS
      sampling depth, orientation of Protein G was successfully determined by analyzing
      the C2H5S+ intensity, a secondary ion derived from a methionine residue located
      at one end of the protein. Next, the secondary structure of a 13-mer leucine
      lysine peptide (LK310) adsorbed onto hydrophilic quartz and hydrophobic
      fluorocarbon surfaces was examined. SFG spectra indicated that the peptide's
      lysine side chains were ordered on the quartz surface, while the peptide's
      leucine side chains were ordered on the fluorocarbon surface. NEXAFS results
      provided complementary information about the structure of the LK310 film and the
      orientations of amide bonds within the LK310 peptide.

PMID- 23976840
TI  - Ultra-high resolution and long scan depth optical coherence tomography with full
      phase detection for imaging the ocular surface.
AB  - We used a unique combination of four state-of-the-art technologies to achieve a
      high performance spectral domain optical coherence tomography system suitable for
      imaging the entire ocular surface. An ultra-high resolution, extended depth
      range, full-phase interferometry, and high-speed complementary metal-oxide
      semiconductor transistor camera detection provided unprecedented performance for
      the precise quantification of a wide range of the ocular surface. We demonstrated
      the feasibility of this approach by obtaining high-speed and high-resolution
      images of a model eye beyond the corneal-scleral junction. Surfaces determined
      from the images with a segmentation algorithm demonstrated excellent accuracy and
      precision. 

PMID- 23976841
TI  - Anterior chamber depth during hemodialysis.
AB  - BACKGROUND: Exacerbation of chronic glaucoma or acute glaucoma is occasionally
      observed in patients undergoing hemodialysis (HD) because of anterior chamber
      depth changes during this therapy. PURPOSE: To evaluate anterior chamber depth
      and axial length in patients during HD sessions. METHODS: A total of 67 eyes of
      35 patients were prospectively enrolled. Axial length and anterior chamber depth
      were measured using ultrasonic biometry, and these measures were evaluated at
      three different times during HD sessions. Body weight and blood pressure pre- and
      post-HD were also measured. RESULTS: There was no difference in the axial length
      between the three measurements (P = 0.241). We observed a significantly decreased
      anterior chamber depth (P = 0.002) during HD sessions. CONCLUSION: Our results
      support the idea that there is a change in anterior chamber depth in HD sessions.

PMID- 23976842
TI  - Drugs in development for treatment of patients with cancer-related anorexia and
      cachexia syndrome.
AB  - Cancer-related anorexia and cachexia syndrome (CACS) is a complex multifactorial
      condition, with loss of lean body mass, chronic inflammation, severe metabolic
      derangements, reduced food intake, reduced physical activity, and poor quality of
      life as key symptoms. Cachexia recognizes different phases or stages, moving from
      precachexia through overt cachexia to advanced or refractory cachexia. The
      purpose of this review is to describe currently effective approaches for the
      treatment of cachexia, moving forward to drugs and treatments already shown to be
      effective but needing further clinical trials to confirm their efficacy. We then
      introduce novel promising investigational drugs and approaches which, based on a
      strong rationale from the most recent data on the molecular targets/pathways
      driving the pathophysiology of cachexia, need to be tested either in currently
      ongoing or appropriate future clinical trials to confirm their clinical
      potential. Although different drugs and treatments have been tested, we can
      speculate that a single therapy may not be completely successful. Indeed,
      considering the complex clinical picture and the multifactorial pathogenesis of
      CACS, we believe that its clinical management requires a multidisciplinary and
      multitargeted approach. In our opinion, appropriate treatment for cachexia should
      target the following conditions: inflammatory status, oxidative stress,
      nutritional disorders, muscle catabolism, immunosuppression, quality of life, and
      above all, fatigue. A comprehensive list of the most interesting and effective
      multitargeted treatments is reported and discussed, with the aim of suggesting
      the most promising with regard to clinical outcome. A critical issue is that of
      testing therapies at the earliest stages of cachexia, possibly at the precachexia
      stage, with the aim of preventing or delaying the development of overt cachexia
      and thereby obtaining the best possible clinical outcome for patients. 

PMID- 23976843
TI  - N-Palmitoylethanolamine depot injection increased its tissue levels and those of
      other acylethanolamide lipids.
AB  - N-Palmitoylethanolamine (NAE 16:0) is an endogenous lipid signaling molecule that
      has limited water solubility, and its action is short-lived due to its rapid
      metabolism. This poses a problem for use in vivo as oral administration requires
      a high concentration for significant levels to reach target tissues, and
      injection of the compound in a dimethyl sulfoxide- or ethanol-based vehicle is
      usually not desirable during long-term treatment. A depot injection of NAE 16:0
      was successfully emulsified in sterile corn oil (10 mg/kg) and administered in
      young DBA/2 mice in order to elevate baseline levels of NAE 16:0 in target
      tissues. NAE 16:0 levels were increased in various tissues, particularly in the
      retina, 24 and 48 hours following injections. Increases ranged between 22% and
      215% (above basal levels) in blood serum, heart, brain, and retina and induced an
      entourage effect by increasing levels of other 18 carbon N-Acylethanolamines
      (NAEs), which ranged between 31% and 117% above baseline. These results indicate
      that NAE 16:0 can be used as a depot preparation, avoiding the use of inadequate
      vehicles, and can provide the basis for designing tissue-specific dosing regimens
      for therapies involving NAEs and related compounds. 

PMID- 23976845
TI  - Erratum: Fixed combination of lercanidipine and enalapril in the management of
      hypertension; focus on patient preference and adherence [Corrigendum].
AB  - [This corrects the article on p. 449 in vol. 6, PMID: 22791982.].

PMID- 23976844
TI  - Valproic acid-associated low fibrinogen and delayed intracranial hemorrhage: case
      report and mini literature review.
AB  - A 41-year-old male had suffered from gradual hearing loss in his right ear for 2
      years. Head computed tomography and magnetic resonance imaging scans showed a
      neoplasm in the cerebellopontine angle region, which was confirmed by the
      diagnosis of acoustic neurilemmoma by pathological findings after surgery.
      Following surgery, he routinely received valproic acid (VPA) to prevent seizures.
      However, the patient presented with hypofibrinogenemia and cerebral hemorrhage
      after taking VPA for 12 days. The hypofibrinogenemia recurred when VPA was re
      administered. After withdrawal of VPA, his fibrinogen concentration rose to
      normal within several days. As far as we are aware, this is the first case of
      cerebral hemorrhage due to VPA to have been reported. Herein, as well as
      reporting on this case, a mini review of the relevant literature is also
      presented. 

PMID- 23976846
TI  - Axial lumbar interbody fusion: a 6-year single-center experience.
AB  - INTRODUCTION: The aim of this study is to report our 6-year single-center
      experience with L5-S1 axial lumbar interbody fusion (AxiaLIF). METHODS: A total
      of 131 patients with symptomatic degenerative disc disease refractory to
      nonsurgical treatment were treated with AxiaLIF at L5-S1, and were followed for a
      minimum of 1 year (mean: 21 months). Main outcomes included back and leg pain
      severity, Oswestry Disability Index score, working status, analgesic medication
      use, patient satisfaction, and complications. Computed tomography was used to
      determine postoperative fusion status. RESULTS: No intraoperative complications,
      including vascular, neural, urologic, or bowel injuries, were reported. Back and
      leg pain severity decreased by 51% and 42%, respectively, during the follow-up
      period (both P < 0.001). Back function scores improved 50% compared to baseline.
      Clinical success, defined as improvement >=30%, was 67% for back pain severity,
      65% for leg pain severity, and 71% for back function. The employment rate
      increased from 47% before surgery to 64% at final follow-up (P < 0.001). Less
      than one in four patients regularly used analgesic medications postsurgery.
      Patient satisfaction with the AxiaLIF procedure was 83%. The fusion rate was
      87.8% at final follow-up. During follow-up, 17 (13.0%) patients underwent 18
      reoperations on the lumbar spine, including pedicle screw fixation (n = 10),
      total disc replacement of an uninvolved level (n = 3), facet screw fixation (n =
      3), facet screw removal (n = 1), and interbody fusion at L4-L5 (n = 1). Eight
      (6.1%) reoperations were at the index level. CONCLUSION: Single-level AxiaLIF is
      a safe and effective means to achieve lumbosacral fusion in patients with
      symptomatic degenerative disc disease.

PMID- 23976847
TI  - Quadriceps femoris muscle fatigue in patients with knee osteoarthritis.
AB  - The purpose of this study was to characterize quadriceps femoris muscle fatigue
      of both lower extremities in patients with knee osteoarthritis (OA). Sixty-two
      subjects (mean age 68.2 years, standard deviation [SD] +/- 7.9 years) with knee
      OA participated in the study. Significantly higher knee pain was reported in the
      involved knee than in the contralateral knee, as determined by a visual analog
      scale. Significant differences were demonstrated between the lower extremities in
      terms of maximal voluntary isometric contraction, in favor of the less involved
      leg (P = 0.0001). In contrast, the degree of fatigue of the quadriceps femoris
      muscle, as measured by the decrement in force production following ten repeated
      contractions, was significantly higher in the contralateral leg (P = 0.0002).
      Furthermore, normalization of the fatigue results to the first contraction
      yielded a similar result (P < 0.0001). Similar results were noted when analysis
      was performed separately for subjects whose involvement was unilateral or
      bilateral. The results indicate that, irrespective of the initial strength of
      contraction, the rate of muscle fatigue in the contralateral leg is significantly
      higher than in the involved leg. Hypotheses for these unexpected results are
      suggested. Rehabilitation of patients with knee OA should focus on increasing
      quadriceps muscle strength and endurance for both lower extremities. 

PMID- 23976848
TI  - Zirconium, calcium, and strontium contents in magnesium based biodegradable
      alloys modulate the efficiency of implant-induced osseointegration.
AB  - Development of new biodegradable implants and devices is necessary to meet the
      increasing needs of regenerative orthopedic procedures. An important
      consideration while formulating new implant materials is that they should
      physicochemically and biologically mimic bone-like properties. In earlier
      studies, we have developed and characterized magnesium based biodegradable
      alloys, in particular magnesium-zirconium (Mg-Zr) alloys. Here we have reported
      the biological properties of four Mg-Zr alloys containing different quantities of
      strontium or calcium. The alloys were implanted in small cavities made in femur
      bones of New Zealand White rabbits, and the quantitative and qualitative
      assessments of newly induced bone tissue were carried out. A total of 30
      experimental animals, three for each implant type, were studied, and bone
      induction was assessed by histological, immunohistochemical and radiological
      methods; cavities in the femurs with no implants and observed for the same period
      of time were kept as controls. Our results showed that Mg-Zr alloys containing
      appropriate quantities of strontium were more efficient in inducing good quality
      mineralized bone than other alloys. Our results have been discussed in the
      context of physicochemical and biological properties of the alloys, and they
      could be very useful in determining the nature of future generations of
      biodegradable orthopedic implants. 

PMID- 23976849
TI  - Process optimization and evaluation of novel baicalin solid nanocrystals.
AB  - The objective of this study was to prepare baicalin solid nanocrystals (BCN-SNS)
      to enhance oral bioavailability of baicalin. A Box-Behnken design approach was
      used for process optimization. The physicochemical properties and
      pharmacokinetics of the optimal BCN-SNS were investigated. Multiple linear
      regression analysis for process optimization revealed that the fine BCN-SNS was
      obtained wherein the optimal values of homogenization pressure (bar),
      homogenization cycles (cycles), amount of TPGS to drug (w/w), and amount of MCCS
      to drug (w/w) were 850 bar, 25 cycles, 10%, and 10%, respectively. Transmission
      electron microscopy and scanning electron microscopy results indicated that no
      significant aggregation or crystal growth could be observed in the redispersed
      freeze-dried BCN-SNS. Differential scanning calorimetry and X-ray diffraction
      results showed that BCN remained in a crystalline state. Dissolution velocity of
      the freeze-dried BCN-SNS powder was distinctly superior compared to those of the
      crude powder and physical mixture. The bioavailability of BCN in rats was
      increased remarkably after oral administration of BCN-SNS (P < 0.05), compared
      with those of BCN or the physical mixture. The SNS might be a good choice for
      oral administration of poorly soluble BCN, due to an improvement of the
      bioavailability and dissolution velocity of BCN-SNS. 

PMID- 23976850
TI  - Long-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles
      containing hydrophobically modified exendin-4 for treating type 2 diabetes.
AB  - Inhalable glycol chitosan-coated poly(lactic-co-glycolic acid) (PLGA)
      nanoparticles containing palmitic acid-modified exendin-4 (Pal-Ex4) (chitosan Pal
      Ex4 PLGA NPs) were prepared and characterized. The surface morphology, particle
      size, and zeta potential of chitosan Pal-Ex4 PLGA NPs were investigated, and the
      adsorption and cytotoxicity of chitosan Pal-Ex4 PLGA NPs were evaluated in human
      lung epithelial cells (A549). Finally, the lung deposition characteristics and
      hypoglycemia caused by chitosan Pal-Ex4 PLGA NPs were evaluated after pulmonary
      administration in imprinting control region (ICR) and type 2 diabetic db/db mice.
      Results showed that chitosan Pal-Ex4 PLGA NPs were spherical, compact and had a
      diameter of ~700 nm and a positive surface charge of +28.5 mV Chitosan-coated
      PLGA NPs were adsorbed onto A549 cells much more so than non-coated PLGA NPs. Pal
      Ex4 release from chitosan-coated PLGA NPs was delayed by as much as 1.5 days as
      compared with chitosan-coated Ex4 PLGA NPs. In addition, chitosan-coated PLGA NPs
      remained in the lungs for ~72 hours after pulmonary administration, whereas most
      non-coated PLGA NPs were lost at 8 hours after administration. Furthermore, the
      hypoglycemic efficacy of inhaled chitosan Pal-Ex4 PLGA NPs was 3.1-fold greater
      than that of chitosan Ex4 PLGA NPs in db/db mice. The authors believe chitosan
      Pal-Ex4 PLGA NPs have considerable potential as a long-acting inhalation delivery
      system for the treatment of type 2 diabetes. 

PMID- 23976852
TI  - Acid-triggered core cross-linked nanomicelles for targeted drug delivery and
      magnetic resonance imaging in liver cancer cells.
AB  - PURPOSE: To research the acid-triggered core cross-linked folate-poly(ethylene
      glycol)-b-poly[N-(N',N'-diisopropylaminoethyl) glutamine] (folated-PEG-P[GA-DIP])
      amphiphilic block copolymer for targeted drug delivery and magnetic resonance
      imaging (MRI) in liver cancer cells. METHODS: As an appropriate receptor of
      protons, the N,N-diisopropyl tertiary amine group (DIP) was chosen to conjugate
      with the side carboxyl groups of poly(ethylene glycol)-b-poly (L-glutamic acid)
      to obtain PEG-P(GA-DIP) amphiphilic block copolymers. By ultrasonic
      emulsification, PEG-P(GA-DIP) could be self-assembled to form nanosized micelles
      loading doxorubicin (DOX) and superparamagnetic iron oxide nanoparticles (SPIONs)
      in aqueous solution. When PEG-P(GA-DIP) nanomicelles were combined with folic
      acid, the targeted effect of folated-PEG-P(GA-DIP) nanomicelles was evident in
      the fluorescence and MRI results. RESULTS: To further increase the loading
      efficiency and the cell-uptake of encapsulated drugs (DOX and SPIONs), DIP
      (pKa~6.3) groups were linked with ~50% of the side carboxyl groups of poly(L
      glutamic acid) (PGA), to generate the core cross-linking under neutral or weakly
      acidic conditions. Under the acidic condition (eg, endosome/lysosome), the
      carboxyl groups were neutralized to facilitate disassembly of the P(GA-DIP)
      blocks' cross-linking, for duly accelerating the encapsulated drug release.
      Combined with the tumor-targeting effect of folic acid, specific drug delivery to
      the liver cancer cells and MRI diagnosis of these cells were greatly enhanced.
      CONCLUSION: Acid-triggered and folate-decorated nanomicelles encapsulating SPIONs
      and DOX, facilitate the targeted MRI diagnosis and therapeutic effects in tumors.

PMID- 23976851
TI  - Advances in drug delivery via electrospun and electrosprayed nanomaterials.
AB  - Electrohydrodynamic (EHD) techniques refer to procedures that utilize
      electrostatic forces to fabricate fibers or particles of different shapes with
      sizes in the nano-range to a few microns through electrically charged fluid jet.
      Employing different techniques, such as blending, surface modification, and
      coaxial process, there is a great possibility of incorporating bioactive such
      molecules as drugs, DNA, and growth factors into the nanostructures fabricated
      via EHD techniques. By careful selection of materials and processing conditions,
      desired encapsulation efficiency as well as preserved bioactivity of the
      therapeutic agents can be achieved. The drug-loaded nanostructures produced can
      be applied via different routes, such as implantation, injection, and topical or
      oral administration for a wide range of disease treatment. Taking advantage of
      the recent developments in EHD techniques like the coaxial process or
      multilayered structures, individually controlled delivery of multiple drugs is
      achievable, which is of great demand in cancer therapy and growth-factor
      delivery. This review summarizes the most recent techniques and postmodification
      methods to fabricate electrospun nanofibers and electrosprayed particles for drug
      delivery applications. 

PMID- 23976853
TI  - Synthesis of novel tetravalent galactosylated DTPA-DSPE and study on hepatocyte
      targeting efficiency in vitro and in vivo.
AB  - For the purposes of obtaining a hepatocyte-selective drug delivery system, a
      novel tetravalent galactosylated diethylenetriaminepentaacetic acid-distearoyl
      phosphatidylethanolamine (4Gal-DTPA-DSPE) was synthesized. The chemical structure
      of 4Gal-DTPA-DSPE was confirmed by proton nuclear magnetic resonance and mass
      spectrometry. The four galactose-modified liposomes (4Gal-liposomes) were
      prepared by thin-film hydration method, then doxorubicin (DOX) was encapsulated
      into liposomes using an ammonium sulfate gradient loading method. The liposomal
      formulations with 4Gal-DTPA-DSPE were characterized by laser confocal scanning
      microscopy and flow cytometry analysis, and the results demonstrated that the
      4Gal-liposomes facilitated the intracellular uptake of DOX into HepG2 cells via
      asialoglycoprotein receptor-mediated endocytosis. Cytotoxicity assay showed that
      the cell proliferation inhibition effect of 4Gal-liposomes was higher than that
      of the conventional liposomes without the galactose. Additionally,
      pharmacokinetic experiments in rats revealed that the 4Gal-liposomes displayed
      slower clearance from the systemic circulation compared with conventional
      liposomes. The organ distributions in mice and the study on frozen sections of
      liver implied that the 4Gal-liposomes enhanced the intracellular uptake of DOX
      into hepatocytes and prolonged the circulation. Taken together, these results
      indicate that liposomes containing 4Gal-DTPA-DSPE have great potential as drug
      delivery carriers for hepatocyte-selective targeting. 

PMID- 23976854
TI  - Neurochemical metabolites in prefrontal cortex in patients with mild/moderate
      levels in first-episode depression.
AB  - BACKGROUND: Previous studies have determined the neurochemical metabolite
      abnormalities in major depressive disorder (MDD). The results of studies are
      inconsistent. Severity of depression may relate to neurochemical metabolic
      changes. The aim of this study is to investigate neurochemical metabolite levels
      in the prefrontal cortex (PFC) of patients with mild/moderate MDD. METHODS:
      Twenty-one patients with mild MDD, 18 patients with moderate MDD, and 16 matched
      control subjects participated in the study. Patients had had their first episode.
      They had not taken treatment. The severity of depression was assessed by the
      Hamilton Rating Scale for Depression (HAM-D). Levels of N-acetyl aspartate (NAA),
      choline-containing compounds (Cho), and creatine-containing compounds (Cr) were
      measured using proton magnetic resonance spectroscopy (1H-MRS) at 1.5 T, with an
      8-cm(3) single voxel placed in the right PFC. RESULTS: The moderate MDD patients
      had lower NAA/Cr levels than the control group. No differences were found in
      neurochemical metabolite levels between the mild MDD and control groups. No
      correlation was found between the patients' neurochemical metabolite levels and
      HAM-D scores. CONCLUSION: Our findings suggest that NAA/Cr levels are low in
      moderate-level MDD in the PFC. Neurochemical metabolite levels did not change in
      mild depressive disorder. Our results suggest that the severity of depression may
      affect neuronal function and viability. Studies are needed to confirm this
      finding, including studies on severely depressive patients.

PMID- 23976855
TI  - Executive dysfunction in children affected by obstructive sleep apnea syndrome:
      an observational study.
AB  - INTRODUCTION: The role of sleep in cognitive processes can be considered clear
      and well established. Different reports have disclosed the association between
      sleep and cognition in adults and in children, as well as the impact of disturbed
      sleep on various aspects of neuropsychological functioning and behavior in
      children and adolescents. Behavioral and cognitive dysfunctions can also be
      considered as related to alterations in the executive functions (EF) system. In
      particular, the EF concept refers to self-regulatory cognitive processes that are
      associated with monitoring and controlling both thought and goal directed
      behaviors. The aim of the present study is to assess the impact of the
      obstructive sleep apnea syndrome (OSAS) on EF in a large sample of school aged
      children. MATERIALS AND METHODS: The study population comprised 79 children (51
      males and 28 females) aged 7-12 years (mean 9.14 +/- 2.36 years) with OSAS and 92
      healthy children (63 males and 29 females, mean age 9.08 +/- 2.44 years). To
      identify the severity of OSAS, an overnight respiratory evaluation was performed.
      All subjects filled out the Italian version of the Modified Card Sorting Test to
      screen EFs. Moreover, to check the degree of subjective perceived daytime
      sleepiness, all subjects were administered the Pediatric Daytime Sleepiness Scale
      (PDSS). RESULTS: No significant differences between the two study groups were
      found for age (P = 0.871), gender (P = 0.704), z-score of body mass index (P =
      0.656), total intelligence quotient (P = 0.358), and PDSS scores (P = 0.232). The
      OSAS children showed a significantly higher rate of total errors (P < 0.001),
      perseverative errors (P < 0.001), nonperseverative errors (P < 0.001), percentage
      of total errors (P < 0.001), percentage of perseverative errors (P < 0.001), and
      percentage of nonperseverative errors (P < 0.001). On the other hand, OSAS
      children showed a significant reduction in the number of completed categories (P
      = 0.036), total correct sorts (P = 0.001), and categorizing efficiency (P <
      0.001). The Pearson's correlation analysis revealed a significant positive
      relationship between all error parameters and apnea-hypopnea index, oxygen
      desaturation index, and percentage of mean desaturation of O2 with a specular
      negative relationship between the error parameters and the mean oxygen saturation
      values, such as a significant negative relationship between apnea-hypopnea index,
      oxygen desaturation index, percent of mean desaturation of O2, and the number of
      completed categories. CONCLUSION: Our study identified differences in the
      executive functioning of children affected by OSAS and is the first to identify a
      correlation between alteration in respiratory nocturnal parameters and EF that
      has not yet been reported in developmental age. These findings can be considered
      as the strength and novelty of the present report in a large pediatric
      population.

PMID- 23976857
TI  - A comparison of complex sleep behaviors with two short-acting Z-hypnosedative
      drugs in nonpsychotic patients.
AB  - OBJECTIVE: Complex sleep behaviors (CSBs) are classified as "parasomnias" in the
      International Classifcation of Sleep Disorders, Second Edition (ICSD-2). To
      realize the potential danger after taking two short-acting Z-hypnosedative drugs,
      we estimated the incidence of CSBs in nonpsychotic patients in Taiwan. METHODS:
      Subjects (N = 1,220) using zolpidem or zopiclone were enrolled from the
      psychiatric outpatient clinics of a medical center in Taiwan over a 16-month
      period in 2006-2007. Subjects with zolpidem (N = 1,132) and subjects with
      zopiclone (N = 88) were analyzed. All subjects completed a questionnaire that
      included demographic data and complex sleep behaviors after taking hypnotics.
      RESULTS: Among zolpidem and zopiclone users, 3.28% of patients reported incidents
      of somnambulism or amnesic sleep-related behavior problems. The incidence of CSBs
      with zolpidem and zopiclone were 3.27%, and 3.41%, respectively, which was
      signifcantly lower than other studies in Taiwan. CONCLUSION: These results serve
      as a reminder for clinicians to make inquiries regarding any unusual performance
      of parasomnic activities when prescribing zolpidem or zopiclone.

PMID- 23976858
TI  - Psychiatrists' awareness of partial and nonadherence to antipsychotic medication
      in schizophrenia: results from an Asia-Pacific survey.
AB  - BACKGROUND: Nonadherence is a well-known problem among schizophrenia patients,
      among whom relapse is fivefold more likely, adversely affecting health,
      employment, and social functioning. The Spanish Adherencia Terapeutica en la
      Esquizofrenia (ADHES) survey was developed to determine the scope and causes of
      medication nonadherence in schizophrenia. METHODS: The 20-question ADHES survey
      was distributed to 19,370 psychiatrists in 13 Asia-Pacific countries in January
      April 2012, to ascertain psychiatrists' perceptions of antipsychotic medication
      adherence levels among their schizophrenia patients, reasons for
      partial/nonadherence, their preferred methods of assessing adherence, and
      strategies to improve adherence. Responses are reported as mean and range across
      countries. RESULTS: Four thousand, six hundred sixty one psychiatrists (24% of
      recipients) completed the survey (highest contributors: People's Republic of
      China, 1854; India, 1616). Psychiatrists perceived that 56% (range, 30%-71%) of
      schizophrenia patients were non- or partially adherent to medication. Patients
      discontinue medication primarily due to lack of insight into their condition
      (mean, 37%; 1%-65%) and because patients consider medication unnecessary when
      feeling better (mean, 27%; 15%-68%). Over half of psychiatrists (mean, 55%; 42%
      99%) assess medication adherence at every visit, almost exclusively (81%) by
      asking their patients, versus quantitative measures. One in three psychiatrists
      expressed their preference to switch to or add a long-acting antipsychotic to
      improve adherence (15%-82%). CONCLUSIONS: The substantial prevalence of
      partial/nonadherence to medication demonstrates that more proactive management of
      patients with schizophrenia is needed to improve adherence and thereby treatment
      outcomes. REGISTRATION: Registration of this study was not required.

PMID- 23976856
TI  - Novel glutamatergic drugs for the treatment of mood disorders.
AB  - Mood disorders are common and debilitating, resulting in a significant public
      health burden. Current treatments are only partly effective and patients who have
      failed to respond to trials of existing antidepressant agents (eg, those who
      suffer from treatment-resistant depression [TRD]) require innovative therapeutics
      with novel mechanisms of action. Although neuroscience research has elucidated
      important aspects of the basic mechanisms of antidepressant action, most
      antidepressant drugs target monoaminergic mechanisms identified decades ago.
      Glutamate, the major excitatory neurotransmitter in the central nervous system,
      and glutamatergic dysfunction has been implicated in mood disorders. These data
      provide a rationale for the pursuit of glutamatergic agents as novel therapeutic
      agents. Here, we review preclinical and clinical investigations of glutamatergic
      agents in mood disorders with a focus on depression. We begin with discussion of
      evidence for the rapid antidepressant effects of ketamine, followed by studies of
      the antidepressant efficacy of the currently marketed drugs riluzole and
      lamotrigine. Promising novel agents currently in development, including N-methyl
      D-aspartate (NMDA) receptor modulators, 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4
      yl) propanoic acid (AMPA) receptor modulators, and drugs with activity at the
      metabotropic glutamate (mGlu) receptors are then reviewed. Taken together, both
      preclinical and clinical evidence exists to support the pursuit of small molecule
      modulators of the glutamate system as novel therapeutic agents in mood disorders.
      It is hoped that by targeting neural systems outside of the monoamine system,
      more effective and perhaps faster acting therapeutics can be developed for
      patients suffering from these disabling disorders. 

PMID- 23976859
TI  - Increased biogenic catecholamine and metabolite levels in two patients with
      malignant catatonia.
AB  - The pathophysiology of malignant catatonia, a rare life-threatening psychiatric
      syndrome, has not yet been elucidated. This paper reports on two patients with
      malignant catatonia who showed elevated urinary or plasma catecholamine levels.
      Patient 1 had high catecholamine and metabolite levels in a 24-hour urine sample,
      and patient 2 had elevated plasma catecholamine levels. These findings indicate
      the presence of peripheral sympathetic nervous system hyperactivity in malignant
      catatonia. Symptoms of autonomic dysfunction, including tachycardia, labile blood
      pressure, and diaphoresis, are typical features of malignant catatonia and may be
      related to the increased levels of biogenic amines in these cases. Although the
      findings in the present study cannot entirely explain the pathophysiology of
      malignant catatonia, they do indicate that hyperactivity of the sympathetic
      nervous system may be involved in the pathology of this condition. 

PMID- 23976861
TI  - Plasminogen activator inhibitor-1, free fatty acids, and insulin resistance in
      patients with myocardial infarction.
AB  - BACKGROUND: Insulin resistance is known to be a common feature of type 2 diabetes
      mellitus and is regarded as an important mechanism in the pathogenesis of this
      disease. The key pathogenetic mechanisms of insulin resistance progression are
      free fatty acids metabolism impairment and enhanced activity of plasminogen
      activator inhibitor 1. Both free fatty acids and plasminogen activator inhibitor
      1 are recognized as risk factors for coronary heart disease. METHODS: THE
      PATIENTS WERE DIVIDED INTO TWO GROUPS: group 1 included 65 non-diabetic
      myocardial infarction patients and group 2 enrolled 60 diabetic myocardial
      infarction patients. The control group consisted of 30 sex- and age-matched
      volunteers. The concentration of serum free fatty acids, glucose, C-peptide, and
      insulin were measured on the 1st and 12th days of the study. All the patients had
      their postprandial glycemia, insulin, and C-peptide concentrations measured 2
      hours after a standard carbohydrate breakfast containing 360 kcal (protein 20 g,
      carbohydrate 57 g, and fat 9 g). RESULTS: Free fatty acids levels in group 1 and
      in group 2 exceeded the control group values by 7-fold and 11-fold, respectively.
      Plasminogen activator inhibitor 1 concentration was 2.5-fold higher in group 1
      and 4.6-fold higher in group 2 compared to the control group on the 1st day from
      the myocardial infarction onset. In addition, plasminogen activator inhibitor 1
      concentration was significantly reduced in both groups on the 12th day from the
      myocardial infarction onset; however, it did not achieve the control group
      values. CONCLUSION: Increased postprandial glucose level, insulinemia, and
      elevated levels of free fatty acids and plasminogen activator inhibitor are
      associated with myocardial infarction-associated progression of insulin
      resistance. However, insulin resistance metabolic markers are of great predictive
      capacity in the assessment of risk of acute coronary events.

PMID- 23976860
TI  - Prognostic value of heart rate turbulence for risk assessment in patients with
      unstable angina and non-ST elevation myocardial infarction.
AB  - BACKGROUND: We sought to examine the prognostic value of heart rate turbulence
      derived from electrocardiographic recordings initiated in the emergency
      department for patients with non-ST elevation myocardial infarction (NSTEMI) or
      unstable angina. METHODS: Twenty-four-hour Holter recordings were started in
      patients with cardiac symptoms approximately 45 minutes after arrival in the
      emergency department. Patients subsequently diagnosed with NSTEMI or unstable
      angina who had recordings with >=18 hours of sinus rhythm and sufficient data to
      compute Thrombolysis In Myocardial Infarction (TIMI) risk scores were chosen for
      analysis (n = 166). Endpoints were emergent re-entry to the cardiac emergency
      department and/or death at 30 days and one year. RESULTS: In Cox regression
      models, heart rate turbulence and TIMI risk scores together were significant
      predictors of 30-day (model chi square 13.200, P = 0.001, C-statistic 0.725) and
      one-year (model chi square 31.160, P < 0.001, C-statistic 0.695) endpoints,
      outperforming either measure alone. CONCLUSION: Measurement of heart rate
      turbulence, initiated upon arrival at the emergency department, may provide
      additional incremental value in the risk assessment for patients with NSTEMI or
      unstable angina.

PMID- 23976862
TI  - Three-year experience of prophylactic placement of inferior vena cava filters in
      women with gynecological cancer.
AB  - OBJECTIVE: To evaluate the outcomes of prophylactic placement of inferior vena
      cava (IVC) filters to prevent pulmonary embolism (PE) in women undergoing surgery
      and chemotherapy for gynecological cancer. METHODS AND MATERIALS: Thirty-eight
      IVC filters were placed in 38 women between January 2008 and January 2010; 25 of
      these were placed in gynecological cancer patients for prevention of PE during
      surgery and the postoperative period. The patients' electronic medical records,
      follow-up computed tomography scans, and outpatient follow-up notes were
      retrospectively reviewed for incidence of PE and adverse events. RESULTS: After 6
      months of follow-up, no PE was observed and there was no mortality. Nine filters
      were retrieved uneventfully, and there were no clinical complications associated
      with any indwelling filter. CONCLUSION: IVC filters are safe and beneficial
      towards preventing PE in women undergoing surgery and chemotherapy for
      gynecological cancer.

PMID- 23976863
TI  - Protocols for treating the postoperative pain of fractures in Dutch hospitals.
AB  - INTRODUCTION: Every year, over 260,000 patients in the Netherlands are diagnosed
      with a traumatic fracture. Many patients are treated surgically and need
      postoperative treatment of pain. Research suggests postoperative pain is often
      under-treated, leaving a significant proportion of patients in moderate to severe
      postoperative pain. Specialized, evidence-based pain-management protocols offer
      patients the best possible pain management, and significantly reduce the risk of
      pain-related health complications. OBJECTIVE: Our objective was to review the
      range of postoperative pain protocols that are currently being used to treat
      postoperative fracture pain within the Netherlands, and investigate whether a
      specialized, evidence-based protocol for treating postoperative fracture pain
      exists within this sample. METHODS: A written request for the protocol currently
      being used for the treatment of postoperative pain following the surgical
      treatment of a fracture was sent to 101 Dutch hospital departments. The
      administration and dosage of pain medications used during postoperative pain
      management were then identified and summarized. RESULTS: Of the contacted
      hospitals, 57% sent in protocols; 45% of these were eligible for analysis. All of
      the departments sent a general or acute pain protocol rather than a specialized
      protocol for the treatment of postoperative pain associated with the surgical
      treatment of fractures. A total of 22 different analgesics were used for pain
      management in 135 different administration schemes. Paracetamol, diclofenac, and
      morphine were used in the majority of protocols. Medication was given via oral,
      rectal, intravenous, subcutaneous, intramuscular, and epidural routes, amongst
      others. CONCLUSION: No specialized, evidence-based protocols for the treatment of
      postoperative fracture pain were found in this Dutch sample. A wide variety of
      medications, dosages, and administration schemes were used to manage
      postoperative pain following the surgical treatment of a fracture. The importance
      of developing a clear, specialized, evidence-based protocol for the treatment of
      postoperative pain following fracture surgery is discussed.

PMID- 23976865
TI  - Positive predictive value of the infant respiratory distress syndrome diagnosis
      in the Danish National Patient Registry.
AB  - BACKGROUND: Infant respiratory distress syndrome (IRDS) is the most common
      respiratory disease in preterm infants, and is associated with considerable
      morbidity and mortality. Valid data on IRDS are important in clinical
      epidemiological research. OBJECTIVES: The objective of this study was to estimate
      the positive predictive value (PPV) of the IRDS diagnosis registered in the
      population-based Danish National Patient Registry according to the International
      Classification of Diseases, 8th and 10th revisions. METHODS: Between January 1,
      1977 and December 31, 2008, we randomly selected three patients per year, 96 in
      total, who were registered with an IRDS diagnosis in the Danish National Patient
      Registry and living in the northern part of Denmark. Data on the infants included
      information on the presence of predefined clinical symptoms. We defined IRDS as
      the presence of at least two of four clinical symptoms (tachypnea, retractions or
      nasal flaring, grunting, and central cyanosis), which had to be present for more
      than 30 minutes. Using medical record review as the reference standard, we
      computed the positive predictive value of the registered IRDS diagnosis including
      95% confidence intervals (CIs). RESULTS: We located the medical record for 90 of
      the 96 patients (94%), and found an overall PPV of the IRDS diagnosis of 81% (95%
      CI 72%-88%). This did not vary substantially between primary and secondary
      diagnoses. The PPV was higher, at 89% (95% CI 80%-95%), for preterm infants born
      before 37 weeks of gestation. CONCLUSION: The PPV of the IRDS diagnosis in the
      Danish National Patient Registry is reasonable when compared with symptoms
      described in the corresponding medical records. The Danish National Patient
      Registry is a useful data source for studies of IRDS, particularly if restricted
      to preterm infants. Nonetheless, the potential impact of misclassification of the
      IRDS diagnosis must be considered.

PMID- 23976864
TI  - Samarium-153-ethylene diamine tetramethylene phosphonate, a beta-emitting bone
      targeted radiopharmaceutical, useful for patients with osteoblastic bone
      metastases.
AB  - Bone metastases are prevalent among cancer patients and frequently cause
      significant morbidity. Oncology providers must mitigate complications associated
      with bone metastases while limiting therapy-related adverse effects and their
      impact on quality of life. Multiple treatment modalities, including chemotherapy,
      surgery, external beam radiation therapy, and radioisotopes, among others, have
      been recommended and utilized for palliative treatment of bone metastases.
      Radioisotopes such as samarium-153 are commonly used in the setting of multifocal
      bone metastases due to their systemic distribution, affinity for osteoblastic
      lesions, acceptable toxicity profile, and convenience of administration. This
      review focuses on samarium-153, first defining its radiobiologic and
      pharmacokinetic properties before describing many clinical trials that support
      its use as a safe and effective tool in the palliation of patients with bone
      metastases. 

PMID- 23976866
TI  - Inadequate pain relief in ambulatory patients with human immunodeficiency virus
      disease in Port Harcourt.
AB  - OBJECTIVES: To estimate the prevalence of pain in ambulatory patients with human
      immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) in Port
      Harcourt and to determine the type, site, severity, and adequacy of the treatment
      of pain in these patients. MATERIALS AND METHODS: A cross-sectional survey was
      carried out at two antiretroviral therapy centers in Port Harcourt, Nigeria. A
      data sheet, the brief pain inventory, and the short form of the McGill pain
      questionnaire were used and 157 patients in various stages of HIV/AIDS
      participated in the study. RESULTS: About 83.7% (129/157) of the ambulatory
      patients with HIV/AIDS complained of pains. Of the patients who reported pain
      61.24% (79/129) reported nociceptive pain while 38.76% (50/129) reported
      neuropathic pain. Chest pain was the most frequent site of pain followed by
      headache. About 82% (106/129) of those who complained of pain received some form
      of analgesic, but only 23.58% (25/106) of these obtained adequate pain relief.
      The majority of the participants had significant impairment of their quality of
      life due to the severity of their pain. CONCLUSION: Pain associated with
      significant impairment of quality of life is common in ambulatory patients with
      HIV/AIDS in Port Harcourt. Whereas the majority of the patients used various pain
      relief methods, analgesia was inadequate.

PMID- 23976867
TI  - HPV infection, cervical abnormalities, and cancer in HIV-infected women in
      Mumbai, India: 12-month follow-up.
AB  - BACKGROUND: HIV-infected women are at a higher risk of cervical intraepithelial
      neoplasia (CIN) and cancer than women in the general population, partly due to a
      high prevalence of persistent human papillomavirus (HPV) infection. The aim of
      the study was to assess the burden of HPV infection, cervical abnormalities, and
      cervical cancer among a cohort of HIV-infected women as part of a routine
      screening in an urban overpopulated slum setting in Mumbai, India. METHODS: From
      May 2010 to October 2010, Medecins Sans Frontieres and Tata Memorial Hospital
      Mumbai offered routine annual Pap smears and HPV DNA testing of women attending
      an antiretroviral therapy (ART) clinic and a 12-month follow-up. Women with
      abnormal test results were offered cervical biopsy and treatment, including
      treatment for sexually transmitted infections (STIs). RESULTS: Ninety-five women
      were screened. Median age was 38 years (IQR: 33-41); median nadir CD4-count 143
      cells/MUL (IQR: 79-270); and median time on ART 23 months (IQR:10-41). HPV DNA
      was detected in 30/94 women (32%), and 18/94 (19%) showed either low-grade or
      high-grade squamous intraepithelial lesions (LSIL/HSIL) on Pap smear. Overall,
      >50% had cervical inflammatory reactions including STIs. Of the 43 women with a
      cervical biopsy, eight (8.4%) had CIN-1, five (5.3%) CIN-2, and two (2.1%)
      carcinoma in situ. All but one had HPV DNA detected (risk ratio: 11, 95%
      confidence interval: 3.3-34). By October 2011, 56 women had completed the 12
      month follow-up and had been rescreened. No new cases of HPV infection/LSIL/HSIL
      were detected. CONCLUSION: The high prevalence of HPV infection, STIs, and
      cervical lesions among women attending an ART clinic demonstrates a need for
      routine screening. Simple, one-stop screening strategies are needed. The optimal
      screening interval, especially when resources are limited, needs to be
      determined.

PMID- 23976868
TI  - High maternal and neonatal mortality rates in northern Nigeria: an 8-month
      observational study.
AB  - BACKGROUND: Despite considerable efforts to reduce the maternal mortality ratio,
      numerous pregnant women continue to die in many developing countries, including
      Nigeria. We conducted a study to determine the incidence and causes of maternal
      mortality over an 8-month period in a rural-based secondary health facility
      located in Jahun, northern Nigeria. METHODS: A retrospective observational study
      was performed in a 41-bed obstetric ward. From October 2010 to May 2011,
      demographic data, obstetric characteristics, and outcome were collected from all
      pregnant women admitted. The total number of live births during the study period
      was recorded in order to calculate the maternal mortality ratio. RESULTS: There
      were 2,177 deliveries and 39 maternal deaths during the study period, with a
      maternal mortality ratio of 1,791/100,000 live births. The most common causes of
      maternal mortality were hemorrhage (26%), puerperal sepsis (19%), and obstructed
      labor (5%). No significant difference (P = 0.07) in mean time to reach the
      hospital was noted between fatal cases (1.9 hours, 95% confidence interval [CI]
      1.1-2.6) and nonfatal cases (1.4 hours, 95% CI 1.4-1.5). Two hundred and sixty
      six women were admitted presenting with stillbirth. Maternal mortality was higher
      for unbooked patients than for booked patients (odds ratio 5.1, 95% CI 3.5-6.2, P
      < 0.0001). The neonatal mortality rate was calculated at 46/1,000 live births.
      The main primary causes of neonatal deaths were prematurity (44%) and birth
      asphyxia (22%). CONCLUSION: Maternal and neonatal mortality remains unacceptably
      high in this setting. Reducing unbooked emergencies should be a priority with
      continuous programs including orthodox practices in order to meet the fifth
      Millennium Development Goal.

PMID- 23976869
TI  - Review of current classification, molecular alterations, and tyrosine kinase
      inhibitor therapies in myeloproliferative disorders with hypereosinophilia.
AB  - Recent advances in our understanding of the molecular mechanisms underlying
      hypereosinophilia have led to the development of a 'molecular' classification of
      myeloproliferative disorders with eosinophilia. The revised 2008 World Health
      Organization classification of myeloid neoplasms included a new category called
      "myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA,
      PDGFRB or FGFR1." Despite the molecular heterogeneity of PDGFR (platelet-derived
      growth factor receptor) rearrangements, tyrosine kinase inhibitors at low dose
      induce rapid and complete hematological remission in the majority of these
      patients. Other kinase inhibitors are promising. Further discoveries of new
      molecular alterations will direct the development of new specific inhibitors. In
      this review, an update of the classifications of myeloproliferative disorders
      associated with hypereosinophilia is discussed together with open and
      controversial questions. Molecular mechanisms and promising results of tyrosine
      kinase inhibitor treatments are reviewed. 

PMID- 23976870
TI  - Short-term training of upper gastrointestinal endoscopy for resident doctors in
      Sotogahama Central Hospital in Aomori, Japan.
AB  - It is essential for young physicians in municipal hospitals to be familiar with
      the technique of upper gastrointestinal (GI) endoscopy. Endoscopy is an exciting
      subspecialty in primary care medicine. Endoscopic procedures are primarily
      performed by general physicians in Japan. However, a standardized strategy for
      teaching diagnostic GI endoscopy is still lacking, and there is not sufficient
      time for young physicians to effectively learn the upper GI endoscopy technique.
      To elucidate how young physicians can be trained in the skills of GI endoscopy in
      a short time period, we initiated a 12-week training course. Two young physicians
      performed upper GI endoscopies for outpatients and inpatients 2 or 3 days a week
      from April 2010 to March 2012. The total number of cases undergoing GI endoscopy
      during the training course in each year was 117 and 111, respectively. The young
      physicians were trained in this technique by the attending physician. The short
      term training course included four phases. During these phases, the young
      physicians learned how to insert the endoscope through the nasal cavity or oral
      cavity into the esophageal inlet, how to pass the endoscope from the esophageal
      inlet into the duodenum, how to take pictures with the endoscope, and how to
      stain the gastric and duodenal mucosa and take mucosal biopsy samples. The young
      physicians experienced 20-30 cases in each phase. In week five, they performed
      endoscope insertion into the duodenum along the folds of the greater curvature of
      the stomach. They viewed the entire stomach and took pictures until week ten of
      the course. The pictures taken in week ten were of a better quality for examining
      the disease lesions than those taken in week six. In the last 2 weeks of the
      training course, the young physicians stained the gastric and duodenal mucosa and
      took mucosal biopsy samples. The short-term training course of 100-120 cases in
      12 weeks was effective for teaching young physicians how to perform GI
      endoscopies independently. 

PMID- 23976871
TI  - Publishing medical schools' USMLE Step 1 scores: increase preclinical education
      accountability and national standards.

PMID- 23976872
TI  - Frequency and Predictability Effects in Eye Fixations for Skilled and Less
      Skilled Deaf Readers.
AB  - The illiteracy rate in the deaf population has been alarmingly high for several
      decades, despite the fact that deaf children go through the standard stages of
      schooling. Much research addressing this issue has focused on word-level
      processes, but in the recent years, little research has focused on sentence
      levels processes. Previous research (Fischler, 1985) investigated word
      integration within context in college-level deaf and hearing readers in a lexical
      decision task following incomplete sentences with targets that were congruous or
      incongruous relative to the preceding context; it was found that deaf readers, as
      a group, were more dependent on contextual information than their hearing
      counterparts. The present experiment extended Fischler's results and investigated
      the relationship between frequency, predictability, and reading skill in skilled
      hearing, skilled deaf, and less-skilled deaf readers. Results suggest that only
      less-skilled deaf readers, and not all deaf readers, rely more on contextual cues
      to boost word processing. Additionally, early effects of frequency and
      predictability were found for all three groups of readers, without any evidence
      for an interaction between frequency and predictability.

PMID- 23976873
TI  - Cell number regulator genes in Prunus provide candidate genes for the control of
      fruit size in sweet and sour cherry.
AB  - Striking increases in fruit size distinguish cultivated descendants from small
      fruited wild progenitors for fleshy fruited species such as Solanum lycopersicum
      (tomato) and Prunus spp. (peach, cherry, plum, and apricot). The first fruit
      weight gene identified as a result of domestication and selection was the tomato
      FW2.2 gene. Members of the FW2.2 gene family in corn (Zea mays) have been named
      CNR (Cell Number Regulator) and two of them exert their effect on organ size by
      modulating cell number. Due to the critical roles of FW2.2/CNR genes in
      regulating cell number and organ size, this family provides an excellent source
      of candidates for fruit size genes in other domesticated species, such as those
      found in the Prunus genus. A total of 23 FW2.2/CNR family members were identified
      in the peach genome, spanning the eight Prunus chromosomes. Two of these CNRs
      were located within confidence intervals of major quantitative trait loci (QTL)
      previously discovered on linkage groups 2 and 6 in sweet cherry (Prunus avium),
      named PavCNR12 and PavCNR20, respectively. An analysis of haplotype, sequence,
      segregation and association with fruit size strongly supports a role of PavCNR12
      in the sweet cherry linkage group 2 fruit size QTL, and this QTL is also likely
      present in sour cherry (P. cerasus). The finding that the increase in fleshy
      fruit size in both tomato and cherry associated with domestication may be due to
      changes in members of a common ancestral gene family supports the notion that
      similar phenotypic changes exhibited by independently domesticated taxa may have
      a common genetic basis.

PMID- 23976874
TI  - Efficacy of pyramiding elite alleles for dynamic development of plant height in
      common wheat.
AB  - Plant height is an important botanical feature closely related to yield. Two
      populations consisting of 118 and 262 accessions respectively were used to
      identify elite alleles for plant height and to validate their allelic effects.
      Plant height was measured from the early booting to the flowering stages. Simple
      sequence repeat markers for candidate quantitative trait locus (QTL) regions with
      large effects identified in a doubled haploid (DH) population (Hanxuan 10 * Lumai
      14) were selected for further verification by association analysis. Nine loci
      significantly (P < 0.001) associated with plant height were detected 13 times in
      the population with 118 accessions. Three loci (Xgwm11-1B, Xwmc349-4B and Xcfd23
      4D) were identified in three, two and two periods of plant height growth,
      respectively. Markers Xbarc168-2D, Xgwm249-2D, Xwmc349-4B, Xcfd23-4D and Xgwm410
      5A located at or near additive QTL regions in the DH population proved to
      coincide with known Rht loci. The results showed a consistency between linkage
      analysis and association mapping, and also confirmed the value of fine mapping of
      QTL through combined linkage and association analyses. For final plant height,
      the alleles Xgwm11-1B208 , Xwmc349-4B103 and Xcfd23-4D202 exhibited negative
      effects, i.e. reducing plant height; Xwmc349-4B101 and Xcfd23-4D205 showed
      significant positive effects. A second larger population (262 accessions) was
      used to validate the effects of these large-effect alleles and the efficacy of
      pyramiding in eight environments (year * site * water regime combinations).
      Strong correlations between final plant height and numbers of large-effect
      alleles indicated that the alleles contributed additively to plant height. The
      additive effects showed that pyramiding elite alleles for target traits has
      significant potential for wheat breeding.

PMID- 23976876
TI  - Plasmon Resonances of Nanoshells of Spheroidal Shape.
AB  - Plasmon resonances are computed for nanoshells of prolate and oblate spheroidal
      shape. Both longitudinal and transverse resonances are investigated as a function
      of aspect ratio and shell thickness. Formulas for the surface charge density on
      the outside and inside shell surfaces are derived.

PMID- 23976875
TI  - Design of siRNA Therapeutics from the Molecular Scale.
AB  - While protein-based therapeutics is well-established in the market, development
      of nucleic acid therapeutics has lagged. Short interfering RNAs (siRNAs)
      represent an exciting new direction for the pharmaceutical industry. These small,
      chemically synthesized RNAs can knock down the expression of target genes through
      the use of a native eukaryotic pathway called RNA interference (RNAi). Though
      siRNAs are routinely used in research studies of eukaryotic biological processes,
      transitioning the technology to the clinic has proven challenging. Early efforts
      to design an siRNA therapeutic have demonstrated the difficulties in generating a
      highly-active siRNA with good specificity and a delivery vehicle that can protect
      the siRNA as it is transported to a specific tissue. In this review article, we
      discuss design considerations for siRNA therapeutics, identifying criteria for
      choosing therapeutic targets, producing highly-active siRNA sequences, and
      designing an optimized delivery vehicle. Taken together, these design
      considerations provide logical guidelines for generating novel siRNA
      therapeutics. 

PMID- 23976877
TI  - The Impact of Acculturation, Motivation and the Therapeutic Alliance on Treatment
      Retention and Outcomes for Hispanic Drug Involved Probationers.
AB  - Factors associated with retention and outcomes for Hispanic offenders mandated to
      treatment for substance use disorders have been overlooked in the literature
      resulting in an impediment to providing evidence-based, culturally relevant
      treatment services. This project examined the roles of motivational factors, the
      therapeutic relationship, and acculturation in predicting treatment retention and
      recidivism among Hispanic male probationers mandated to residential treatment. By
      following a treatment cohort over one hundred and twenty days, this research
      identifies factors that may be targeted to improve interventions and policies.
      The following conclusions are supported: among Hispanic offenders, the number of
      days in treatment is positively related to motivation to change and level of
      acculturation.

PMID- 23976878
TI  - Mom knows best: the universality of maternal microbial transmission.
AB  - The sterile womb paradigm is an enduring premise in biology that human infants
      are born sterile. Recent studies suggest that infants incorporate an initial
      microbiome before birth and receive copious supplementation of maternal microbes
      through birth and breastfeeding. Moreover, evidence for microbial maternal
      transmission is increasingly widespread across animals. This collective knowledge
      compels a paradigm shift-one in which maternal transmission of microbes advances
      from a taxonomically specialized phenomenon to a universal one in animals. It
      also engenders fresh views on the assembly of the microbiome, its role in animal
      evolution, and applications to human health and disease.

PMID- 23976879
TI  - Hybrid T-helper cells: stabilizing the moderate center in a polarized system.
AB  - Polarization of cell phenotypes, a common strategy to achieve cell type diversity
      in metazoa, results from binary cell-fate decisions in the branching pedigree of
      development. Such "either-or" fate decisions are controlled by two opposing cell
      fate-determining transcription factors. Each of the two distinct "master
      regulators" promotes differentiation of its respective sister lineage. But they
      also suppress one other, leading to their mutually exclusive expression in the
      two ensuing lineages. Thus, promiscuous coexistence of the antagonist regulators
      in the same cell, the hallmark of the common "undecided" progenitor of two sister
      lineages, is considered unstable. This antagonism ensures robust polarization
      into two discretely distinct cell types. But now the immune system's T-helper
      (Th) cells and their two canonical subtypes, Th1 and Th2 cells, tell a different
      story, as revealed in three papers recently published in PLOS Biology. The
      intermediate state that co-expresses the two opposing master regulators of the
      Th1 and Th2 subtypes, T-bet and Gata3, is highly stable and is not necessarily an
      undecided precursor. Instead, the Th1/Th2 hybrid cell is a robust new type with
      properties of both Th1 and Th2 cells. These hybrid cells are functionally active
      and possess the benefit of moderation: self-limitation of effector T cell
      function to prevent excessive inflammation, a permanent risk in host defense that
      can cause tissue damage or autoimmunity. Gene regulatory network analysis
      suggests that stabilization of the intermediate center in a polarizing system can
      be achieved by minor tweaking of the architecture of the mutual suppression gene
      circuit, and thus is a design option readily available to evolution. 

PMID- 23976880
TI  - Stable T-bet(+)GATA-3(+) Th1/Th2 hybrid cells arise in vivo, can develop directly
      from naive precursors, and limit immunopathologic inflammation.
AB  - Differentiated T helper (Th) cell lineages are thought to emerge from alternative
      cell fate decisions. However, recent studies indicated that differentiated Th
      cells can adopt mixed phenotypes during secondary immunological challenges. Here
      we show that natural primary immune responses against parasites generate
      bifunctional Th1 and Th2 hybrid cells that co-express the lineage-specifying
      transcription factors T-bet and GATA-3 and co-produce Th1 and Th2 cytokines. The
      integration of Th1-promoting interferon (IFN)-gamma and interleukin (IL)-12
      signals together with Th2-favoring IL-4 signals commits naive Th cells directly
      and homogeneously to the hybrid Th1/2 phenotype. Specifically, IFN-gamma signals
      are essential for T-bet(+)GATA-3(+) cells to develop in vitro and in vivo by
      breaking the dominance of IL-4 over IL-12 signals. The hybrid Th1/2 phenotype is
      stably maintained in memory cells in vivo for months. It resists reprogramming
      into classic Th1 or Th2 cells by Th1- or Th2-promoting stimuli, which rather
      induce quantitative modulations of the combined Th1 and Th2 programs without
      abolishing either. The hybrid phenotype is associated with intermediate
      manifestations of both Th1 and Th2 cell properties. Consistently, hybrid Th1/2
      cells support inflammatory type-1 and type-2 immune responses but cause less
      immunopathology than Th1 and Th2 cells, respectively. Thus, we propose the self
      limitation of effector T cells based on the stable cell-intrinsic balance of two
      opposing differentiation programs as a novel concept of how the immune system can
      prevent excessive inflammation. 

PMID- 23976881
TI  - The HILDA complex coordinates a conditional switch in the 3'-untranslated region
      of the VEGFA mRNA.
AB  - Cell regulatory circuits integrate diverse, and sometimes conflicting,
      environmental cues to generate appropriate, condition-dependent responses. Here,
      we elucidate the components and mechanisms driving a protein-directed RNA switch
      in the 3'UTR of vascular endothelial growth factor (VEGF)-A. We describe a novel
      HILDA (hypoxia-inducible hnRNP L-DRBP76-hnRNP A2/B1) complex that coordinates a
      three-element RNA switch, enabling VEGFA mRNA translation during combined hypoxia
      and inflammation. In addition to binding the CA-rich element (CARE),
      heterogeneous nuclear ribonucleoprotein (hnRNP) L regulates switch assembly and
      function. hnRNP L undergoes two previously unrecognized, condition-dependent
      posttranslational modifications: IFN-gamma induces prolyl hydroxylation and von
      Hippel-Lindau (VHL)-mediated proteasomal degradation, whereas hypoxia stimulates
      hnRNP L phosphorylation at Tyr(359), inducing binding to hnRNP A2/B1, which
      stabilizes the protein. Also, phospho-hnRNP L recruits DRBP76 (double-stranded
      RNA binding protein 76) to the 3'UTR, where it binds an adjacent AU-rich stem
      loop (AUSL) element, "flipping" the RNA switch by disrupting the GAIT (interferon
      gamma-activated inhibitor of translation) element, preventing GAIT complex
      binding, and driving robust VEGFA mRNA translation. The signal-dependent, HILDA
      complex coordinates the function of a trio of neighboring RNA elements, thereby
      regulating translation of VEGFA and potentially other mRNA targets. The VEGFA RNA
      switch might function to ensure appropriate angiogenesis and tissue oxygenation
      during conflicting signals from combined inflammation and hypoxia. We propose the
      VEGFA RNA switch as an archetype for signal-activated, protein-directed, multi
      element RNA switches that regulate posttranscriptional gene expression in complex
      environments. 

PMID- 23976882
TI  - Effects of diet on resource utilization by a model human gut microbiota
      containing Bacteroides cellulosilyticus WH2, a symbiont with an extensive
      glycobiome.
AB  - The human gut microbiota is an important metabolic organ, yet little is known
      about how its individual species interact, establish dominant positions, and
      respond to changes in environmental factors such as diet. In this study,
      gnotobiotic mice were colonized with an artificial microbiota comprising 12
      sequenced human gut bacterial species and fed oscillating diets of disparate
      composition. Rapid, reproducible, and reversible changes in the structure of this
      assemblage were observed. Time-series microbial RNA-Seq analyses revealed
      staggered functional responses to diet shifts throughout the assemblage that were
      heavily focused on carbohydrate and amino acid metabolism. High-resolution
      shotgun metaproteomics confirmed many of these responses at a protein level. One
      member, Bacteroides cellulosilyticus WH2, proved exceptionally fit regardless of
      diet. Its genome encoded more carbohydrate active enzymes than any previously
      sequenced member of the Bacteroidetes. Transcriptional profiling indicated that
      B. cellulosilyticus WH2 is an adaptive forager that tailors its versatile
      carbohydrate utilization strategy to available dietary polysaccharides, with a
      strong emphasis on plant-derived xylans abundant in dietary staples like cereal
      grains. Two highly expressed, diet-specific polysaccharide utilization loci
      (PULs) in B. cellulosilyticus WH2 were identified, one with characteristics of
      xylan utilization systems. Introduction of a B. cellulosilyticus WH2 library
      comprising >90,000 isogenic transposon mutants into gnotobiotic mice, along with
      the other artificial community members, confirmed that these loci represent
      critical diet-specific fitness determinants. Carbohydrates that trigger dramatic
      increases in expression of these two loci and many of the organism's 111 other
      predicted PULs were identified by RNA-Seq during in vitro growth on 31 distinct
      carbohydrate substrates, allowing us to better interpret in vivo RNA-Seq and
      proteomics data. These results offer insight into how gut microbes adapt to
      dietary perturbations at both a community level and from the perspective of a
      well-adapted symbiont with exceptional saccharolytic capabilities, and illustrate
      the value of artificial communities. 

PMID- 23976883
TI  - Effect of household-based drinking water chlorination on diarrhoea among children
      under five in Orissa, India: a double-blind randomised placebo-controlled trial.
AB  - BACKGROUND: Boiling, disinfecting, and filtering water within the home can
      improve the microbiological quality of drinking water among the hundreds of
      millions of people who rely on unsafe water supplies. However, the impact of
      these interventions on diarrhoea is unclear. Most studies using open trial
      designs have reported a protective effect on diarrhoea while blinded studies of
      household water treatment in low-income settings have found no such effect.
      However, none of those studies were powered to detect an impact among children
      under five and participants were followed-up over short periods of time. The aim
      of this study was to measure the effect of in-home water disinfection on
      diarrhoea among children under five. METHODS AND FINDINGS: We conducted a double
      blind randomised controlled trial between November 2010 and December 2011. The
      study included 2,163 households and 2,986 children under five in rural and urban
      communities of Orissa, India. The intervention consisted of an intensive
      promotion campaign and free distribution of sodium dichloroisocyanurate (NaDCC)
      tablets during bi-monthly households visits. An independent evaluation team
      visited households monthly for one year to collect health data and water samples.
      The primary outcome was the longitudinal prevalence of diarrhoea (3-day point
      prevalence) among children aged under five. Weight-for-age was also measured at
      each visit to assess its potential as a proxy marker for diarrhoea. Adherence was
      monitored each month through caregiver's reports and the presence of residual
      free chlorine in the child's drinking water at the time of visit. On 20% of the
      total household visits, children's drinking water was assayed for thermotolerant
      coliforms (TTC), an indicator of faecal contamination. The primary analysis was
      on an intention-to-treat basis. Binomial regression with a log link function and
      robust standard errors was used to compare prevalence of diarrhoea between arms.
      We used generalised estimating equations to account for clustering at the
      household level. The impact of the intervention on weight-for-age z scores (WAZ)
      was analysed using random effect linear regression. Over the follow-up period,
      84,391 child-days of observations were recorded, representing 88% of total
      possible child-days of observation. The longitudinal prevalence of diarrhoea
      among intervention children was 1.69% compared to 1.74% among controls. After
      adjusting for clustering within household, the prevalence ratio of the
      intervention to control was 0.95 (95% CI 0.79-1.13). The mean WAZ was similar
      among children of the intervention and control groups (-1.586 versus -1.589,
      respectively). Among intervention households, 51% reported their child's drinking
      water to be treated with the tablets at the time of visit, though only 32% of
      water samples tested positive for residual chlorine. Faecal contamination of
      drinking water was lower among intervention households than controls (geometric
      mean TTC count of 50 [95% CI 44-57] per 100 ml compared to 122 [95% CI 107-139]
      per 100 ml among controls [p<0.001] [n = 4,546]). CONCLUSIONS: Our study was
      designed to overcome the shortcomings of previous double-blinded trials of
      household water treatment in low-income settings. The sample size was larger, the
      follow-up period longer, both urban and rural populations were included, and
      adherence and water quality were monitored extensively over time. These results
      provide no evidence that the intervention was protective against diarrhoea. Low
      compliance and modest reduction in water contamination may have contributed to
      the lack of effect. However, our findings are consistent with other blinded
      studies of similar interventions and raise additional questions about the actual
      health impact of household water treatment under these conditions. TRIAL
      REGISTRATION: ClinicalTrials.govNCT01202383 Please see later in the article for
      the Editors' Summary.

PMID- 23976884
TI  - Country contextualization of the mental health gap action programme intervention
      guide: a case study from Nigeria.

PMID- 23976886
TI  - Structure, Stiffness and Substates of the Dickerson-Drew Dodecamer.
AB  - The Dickerson-Drew dodecamer (DD) d-[CGCGAATTCGCG]2 is a prototypic B-DNA
      molecule whose sequence-specific structure and dynamics have been investigated by
      many experimental and computational studies. Here, we present an analysis of DD
      properties based on extensive atomistic molecular dynamics (MD) simulations using
      different ionic conditions and water models. The 0.6-2.4-us-long MD trajectories
      are compared to modern crystallographic and NMR data. In the simulations, the
      duplex ends can adopt an alternative base-pairing, which influences the oligomer
      structure. A clear relationship between the BI/BII backbone substates and the
      basepair step conformation has been identified, extending previous findings and
      exposing an interesting structural polymorphism in the helix. For a given end
      pairing, distributions of the basepair step coordinates can be decomposed into
      Gaussian-like components associated with the BI/BII backbone states. The nonlocal
      stiffness matrices for a rigid-base mechanical model of DD are reported for the
      first time, suggesting salient stiffness features of the central A-tract. The
      Riemann distance and Kullback-Leibler divergence are used for stiffness matrix
      comparison. The basic structural parameters converge very well within 300 ns,
      convergence of the BI/BII populations and stiffness matrices is less sharp. Our
      work presents new findings about the DD structural dynamics, mechanical
      properties, and the coupling between basepair and backbone configurations,
      including their statistical reliability. The results may also be useful for
      optimizing future force fields for DNA.

PMID- 23976888
TI  - Theoretical Simulation and Focused Ion Beam Fabrication of Gold Nanostructures
      For Surface-Enhanced Raman Scattering (SERS).
AB  - This paper describes the fabrication of gold nanopillar and nanorod arrays and
      theoretical calculations of electromagnetic fields (EMFs) around ordered
      arrangements of these nanostructures. The EMFs of both single nanopillars and di
      mers of nanopillars - having nanoscale gaps between the two adjacent nanopillars
      forming the di-mers - are simulated in this work by employing the Finite
      Difference Time Domain (FDTD) method. In the case of simulations for di-mers of
      nanopillars, the nano-scale gaps between the nanopillars are varied between 5 nm
      and 20 nm and calculations of the electromagnetic fields in the vicinity of the
      nanopillars and in the gaps between the nanopillars were carried out. Fabrication
      of gold nanopillars in a controlled manner for forming SERS substrates involves
      focused ion beam (FIB) milling. The nanostructures were fabricated on gold-coated
      silica, mica, and quartz planar substrates as well as on gold-coated tips of four
      mode and multimode silica optical fibers.

PMID- 23976887
TI  - Implementing Residential Integrated Treatment for Co-occurring Disorders.
AB  - Objective: Much is now known about effective treatment for co-occurring substance
      abuse and psychiatric difficulties and many evidence-based practice
      recommendations have been disseminated. Implementation of these recommended
      interventions in daily clinical practice has been more of a struggle. This
      article describes successful implementation of integrated treatment for co
      occurring disorders in a small residential program. Methods: A traditional 28-day
      addiction service was transformed into a 3-month integrated treatment program and
      155 individuals with co-occurring disorders agreed to participate in its
      evaluation. The transformation entailed a completely new manualized service,
      training in a number of clinical interventions for all program clinicians,
      ongoing clinical supervision, and formal measurement of clients' backgrounds,
      substance abuse, quality of life, mental health symptoms, self-esteem, and
      satisfaction with the program. We also obtained collateral informants' reports on
      participants' symptoms, substance use, and quality of life. Fidelity to the
      treatment model was continuously assessed, as were participants' knowledge and
      skill acquisition. In addition, impact of the implementation on the program
      clinicians' morale and attitudes toward evidence-based practices was assessed, as
      was staff turnover and per diem costs. Results: Despite very problematic clinical
      and sociodemographic histories, the 86 participants who completed the program
      showed clinically significant mental health symptom improvement, acquisition of
      knowledge and skill, and high self-esteem and satisfaction with the program.
      Program fidelity, clinician morale, commitment to the program, and attitudes
      toward evidence-based practice were uniformly high. These successes were achieved
      while maintaining the lowest per-inpatient day cost of all hospital inpatient
      units. Conclusions: The findings support the contention that evidence-based
      integrated treatment can be implemented with fidelity in regular clinical
      practice to the benefit of participants, staff, and the hospital. Our experience
      was that having a scientist-practitioner working as a staff member on the program
      to lead the implementation was a key element. Future reports will focus on longer
      term follow-up of substance use and quality of life outcomes.

PMID- 23976889
TI  - Heart Motion Prediction Based on Adaptive Estimation Algorithms for Robotic
      Assisted Beating Heart Surgery.
AB  - Robotic assisted beating heart surgery aims to allow surgeons to operate on a
      beating heart without stabilizers as if the heart is stationary. The robot
      actively cancels heart motion by closely following a point of interest (POI) on
      the heart surface-a process called Active Relative Motion Canceling (ARMC). Due
      to the high bandwidth of the POI motion, it is necessary to supply the controller
      with an estimate of the immediate future of the POI motion over a prediction
      horizon in order to achieve sufficient tracking accuracy. In this paper, two
      least-square based prediction algorithms, using an adaptive filter to generate
      future position estimates, are implemented and studied. The first method assumes
      a linear system relation between the consecutive samples in the prediction
      horizon. On the contrary, the second method performs this parametrization
      independently for each point over the whole the horizon. The effects of predictor
      parameters and variations in heart rate on tracking performance are studied with
      constant and varying heart rate data. The predictors are evaluated using a 3
      degrees of freedom test-bed and prerecorded in-vivo motion data. Then, the one
      step prediction and tracking performances of the presented approaches are
      compared with an Extended Kalman Filter predictor. Finally, the essential
      features of the proposed prediction algorithms are summarized.

PMID- 23976885
TI  - Risk of early-onset neonatal infection with maternal infection or colonization: a
      global systematic review and meta-analysis.
AB  - BACKGROUND: Neonatal infections cause a significant proportion of deaths in the
      first week of life, yet little is known about risk factors and pathways of
      transmission for early-onset neonatal sepsis globally. We aimed to estimate the
      risk of neonatal infection (excluding sexually transmitted diseases [STDs] or
      congenital infections) in the first seven days of life among newborns of mothers
      with bacterial infection or colonization during the intrapartum period. METHODS
      AND FINDINGS: We searched PubMed, Embase, Scopus, Web of Science, Cochrane
      Library, and the World Health Organization Regional Databases for studies of
      maternal infection, vertical transmission, and neonatal infection published from
      January 1, 1960 to March 30, 2013. Studies were included that reported effect
      measures on the risk of neonatal infection among newborns exposed to maternal
      infection. Random effects meta-analyses were used to pool data and calculate the
      odds ratio estimates of risk of infection. Eighty-three studies met the inclusion
      criteria. Seven studies (8.4%) were from high neonatal mortality settings.
      Considerable heterogeneity existed between studies given the various definitions
      of laboratory-confirmed and clinical signs of infection, as well as for
      colonization and risk factors. The odds ratio for neonatal lab-confirmed
      infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI
      3.9-11.2). Newborns of mothers with colonization had a 9.4 (95% CI 3.1-28.5)
      times higher odds of lab-confirmed infection than newborns of non-colonized
      mothers. Newborns of mothers with risk factors for infection (defined as
      prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM)
      had a 2.3 (95% CI 1.0-5.4) times higher odds of infection than newborns of
      mothers without risk factors. CONCLUSIONS: Neonatal infection in the first week
      of life is associated with maternal infection and colonization. High-quality
      studies, particularly from settings with high neonatal mortality, are needed to
      determine whether targeting treatment of maternal infections or colonization,
      and/or prophylactic antibiotic treatment of newborns of high risk mothers, may
      prevent a significant proportion of early-onset neonatal sepsis. Please see later
      in the article for the Editors' Summary.

PMID- 23976890
TI  - The Evolution of Altruistic Preferences: Mothers versus Fathers.
AB  - What can evolutionary biology tell us about male-female differences in
      preferences concerning family matters? Might mothers be more solicitous toward
      offspring than fathers, for example? The economics literature has documented
      gender differences-children benefit more from money put in the hands of mothers
      rather than fathers, for example-and these differences are thought to be partly
      due to preferences. Yet for good reason family economics is mostly concerned with
      how prices and incomes affect behavior against a backdrop of exogenous
      preferences. Evolutionary biology complements this approach by treating
      preferences as the outcome of natural selection. We mine the well-developed
      biological literature to make a prima facie case for evolutionary roots of
      parental preferences. We consider the most rudimentary of traits-sex differences
      in gamete size and internal fertilization-and explain how they have been thought
      to generate male-female differences in altruism toward children and other
      preferences related to family behavior. The evolutionary approach to the family
      illuminates connections between issues typically thought distinct in family
      economics, such as parental care and marriage markets.

PMID- 23976892
TI  - Ellipsoidal Polyaspartamide Polymersomes with Enhanced Cell-Targeting Ability.
AB  - Nano-sized polymersomes functionalized with peptides or proteins are being
      increasingly studied for targeted delivery of diagnostic and therapeutic
      molecules. Earlier computational studies have suggested that ellipsoidal
      nanoparticles, compared to spherical ones, display enhanced binding efficiency
      with target cells, but this has not yet been experimentally validated. We
      hypothesize that hydrophilic polymer chains coupled to vesicle-forming polymers
      would result in ellipsoidal polymersomes. In addition, ellipsoidal polymersomes
      modified with cell adhesion peptides bind with target cells more actively than
      spherical ones. We examine this hypothesis by substituting polyaspartamide with
      octadecyl chains and varying numbers of poly(ethylene glycol) (PEG) chains.
      Increasing the degree of substitution of PEG from 0.5 to 1.0 mol% drives the
      polymer to self-assemble into an ellipsoidal polymersome with an aspect ratio of
      2.1. Further modification of these ellipsoidal polymersomes with peptides
      containing an Arg-Gly-Asp sequence (RGD peptides) lead to a significant increase
      in the rate of association and decrease in the rate of dissociation with a
      substrate coated with alphavbeta3 integrins. In addition, in a circulation
      mimicking flow, the ellipsoidal polymersomes linked with RGD peptides adhere to
      target tissues more favorably than their spherical equivalents do. Overall, the
      results of this study will greatly serve to improve the efficiency of targeted
      delivery of a wide array of polymersomes loaded with various biomedical
      modalities.

PMID- 23976891
TI  - Relationships between Cerebral Blood Flow and IQ in Typically Developing Children
      and Adolescents.
AB  - The objective of this study was to explore the relationships between IQ and
      cerebral blood flow (CBF) measured by arterial spin labeling (ASL) in children
      and adolescents. ASL was used to collect perfusion MRI data on 39 healthy
      participants aged 7 to 17. The Wechsler Abbreviated Intelligence Scale was
      administered to determine IQ scores. Multivariate regression was applied to
      reveal correlations between CBF and IQ scores, accounting for age, sex and global
      mean CBF. Voxel Based Morphometry (VBM) analysis, which measures regional
      cortical volume, was performed as a control. Regression analyses were further
      performed on CBF data with adjustment of regional gray matter density (GMD). A
      positive correlation between CBF and IQ scores was primarily seen in the
      subgenual/anterior cingulate, right orbitofrontal, superior temporal and right
      inferior parietal regions. An inverse relationship between CBF and IQ was mainly
      observed in bilateral posterior temporal regions. After adjusting for regional
      GMD, the correlations between CBF and IQ in the subgenual/anterior cingulate
      cortex, right orbitofrontal, superior temporal regions and left insula remained
      significant. These findings support the Parieto-Frontal Integration Theory of
      intelligence, especially the role of the subgenual/anterior cingulate cortex in
      the neural networks associated with intelligence. The present study also
      demonstrates the unique value of CBF in assessing brain-behavior relationships,
      in addition to structural morphometric measures.

PMID- 23976893
TI  - Computation of kinetic isotope effects for enzymatic reactions.
AB  - We describe a computational approach, incorporating quantum mechanics into enzyme
      kinetics modeling with a special emphasis on computation of kinetic isotope
      effects. Two aspects are highlighted: (1) the potential energy surface is
      represented by a combined quantum mechanical and molecular mechanical (QM/MM)
      potential in which the bond forming and breaking processes are modeled by
      electronic structure theory, and (2) a free energy perturbation method in path
      integral simulation is used to determine both kinetic isotope effects (KIEs). In
      this approach, which is called the PI-FEP/UM method, a light (heavy) isotope is
      mutated into a heavy (light) counterpart in centroid path integral simulations.
      The method is illustrated in the study of primary and secondary KIEs in two
      enzyme systems. In the case of nitroalkane oxidase, the enzymatic reaction
      exhibits enhanced quantum tunneling over that of the uncatalyzed process in
      water. In the dopa delarboxylase reaction, there appears to be distinguishable
      primary carbon-13 and secondary deuterium KIEs when the internal proton
      tautomerism is in the N-protonated or in the O-protonated positions. These
      examples show that the incorporation of quantum mechanical effects in enzyme
      kinetics modeling offers an opportunity to accurately and reliably model the
      mechanisms and free energies of enzymatic reactions.

PMID- 23976895
TI  - High risk human papillomavirus type 16 and 18 infection in the cervical lesions
      of women with epithelial cell abnormality in Pap smear: A cytohistomorphologic
      association in Bangladeshi women.
AB  - BACKGROUND: The aim of this study was to find out the extent of high-risk human
      papillomavirus (hrHPV) type 16/18 infection in the cervical tissue of women with
      epithelial cell abnormality in Pap smear and to establish an association between
      hrHPV type 16/18 infection and cytohistomorphology. MATERIALS AND METHODS: A
      cross-sectional descriptive study was carried out in 1699 patients who went
      through Pap smear examination. Prevalence of epithelial cell abnormality was
      calculated. Forty eight of these women underwent routine histopathology and 47
      were evaluated for human papillomavirus (HPV) type 16/18 by polymerase chain
      reaction assay. RESULTS: Total 139 women revealed epithelial cell abnormality.
      Histopathology showed simple inflammation to malignancy. HPV type 16/18 infection
      was detected in 40.42% (19/47) of the patients. Individually type 16 and 18 were
      positive in 7 (14.9%) cases each and dual infection with type 16 and 18 were seen
      in 5 (10.6%) cases. While cervical intraepithelial neoplasia grade 1 (CIN 1) and
      < CIN 1 lesions showed 18.75% (3 out of 16) and 35% (7 out of 20) positivity
      respectively, >=CIN 2 lesions revealed positivity of 81.82% (9 out of 11). Eighty
      percent HPV 16/18 positivity was seen in women of < 30 years of age. CONCLUSION:
      The findings of this study will contribute to HPV 16/18 knowledge in Bangladesh
      that will be useful in assessing the success of current vaccines with limited
      type spectra and augmenting cervical cancer screening strategies.

PMID- 23976894
TI  - Modulation of Asthma Pathogenesis by Nitric Oxide Pathways and Therapeutic
      Opportunities.
AB  - Asthma, a chronic airway inflammatory disease is typically associated with high
      levels of exhaled nitric oxide (NO). Over the past decades, extensive research
      has revealed that NO participates in a number of metabolic pathways that
      contribute to animal models of asthma and human asthma. In asthmatic airway, high
      levels of NO lead to greater formation of reactive nitrogen species (RNS), which
      modify proteins adversely affecting functional activities. In contrast, high
      levels of NO are associated with lower than normal levels of S-nitrosothiols,
      which serve a bronchodilator function in the airway. Detailed mechanistic studies
      have enabled the development of compounds that target NO metabolic pathways, and
      provide opportunities for novel asthma therapy. This review discusses the role of
      NO in asthma with the primary focus on therapeutic opportunities developed in
      recent years.

PMID- 23976896
TI  - Indications for renal fine needle aspiration biopsy in the era of modern imaging
      modalities.
AB  - BACKGROUND: Renal fine needle aspiration biopsy (FNAB) has become an uncommon
      procedure in the era of renal helical computed tomography (CT), which has high
      diagnostic accuracy in the characterization of renal cortical lesions. This study
      investigates the current indications for renal FNAB. Having knowledge of the
      specific clinico-radiologic scenario that led to the FNAB, cytopathologists are
      better equipped to expand or narrow down their differential diagnosis. MATERIALS
      AND METHODS: All renal FNABs performed during a 6 year interval were retrieved.
      Indication for the procedure was determined from the clinical notes and radiology
      reports. RESULTS: Forty six renal FNABs were retrieved from 43 patients (14
      females and 29 males with a mean age of 52 years [range, 4-81 years]). Twenty one
      cases (45.6%) were performed under CT-guidance and 25 cases (54.4%) under US
      guidance. There were four distinct indications for renal FNAB: (1) solid renal
      masses with atypical radiological features or poorly characterized on imaging
      studies due to lack of intravenous contrast or body habitus (30.2%); (2)
      confirmation of radiologically suspected renal cell carcinoma in inoperable
      patients (advanced stage disease or poor surgical candidate status) (27.9%); (3)
      kidney mass in a patient with a prior history of other malignancy (27.9%); and
      (4) miscellaneous (drainage of abscess, indeterminate cystic lesion, urothelial
      carcinoma) (14.0%). 36 patients (83.7%) received a specific diagnosis based on
      renal FNAB cytology. CONCLUSIONS: Currently, renal fine needle aspiration remains
      a useful diagnostic tool in selected clinico-radiologic scenarios.

PMID- 23976897
TI  - Nanoparticle Formation from Hybrid, Multiblock Copolymers of Poly(Acrylic Acid)
      and VPGVG Peptide.
AB  - Elastin-mimetic hybrid copolymers with an alternating molecular architecture were
      synthesized via the step growth polymerization of azide-functionalized,
      telechelic poly(tert-butyl acrylate) (PtBA) and an alkyne-terminated, valine and
      glycine-rich peptide with a sequence of (VPGVG)2 (VG2). The resultant hybrid
      copolymer, [PtBA-VG2]n, contains up to six constituent building blocks and has a
      polydispersity index (PDI) of ~1.9. Trifluoroacetic acid (TFA) treatment of [PtBA
      VG2]n gave rise to an alternating copolymer of poly(acrylic acid) (PAA) and VG2
      ([PAA-VG2]n). The modular design permits facile adjustment of the copolymer
      composition by varying the molecular weight of PAA (22 and 63 repeat units).
      Characterization by dynamic light scattering indicated that the multiblock
      copolymers formed discrete nanoparticles at room temperature in aqueous solution
      at pH 3.8, with an average diameter of 250-270 nm and a particle size
      distribution of 0.34 for multiblock copolymers containing PAA22 and 0.17 for
      those containing PAA63. Upon increasing the pH to 7.4, both types of particles
      were able to swell without being disintegrated, reaching an average diameter of
      285-300 nm for [PAA22-VG2]n and 330-350 nm for [PAA63-VG2]n, respectively. The
      nanoparticles were not dissociated upon the addition of urea, further confirming
      their unusual stability. The nanoparticles were capable of sequestering a
      hydrophobic fluorescent dye (pyrene), and the critical aggregation concentration
      (CAC) was determined to be 1.09 * 10-2 or 1.05 * 10-2 mg/mL for [PAA22-VG2]n and
      [PAA63-VG2]n, respectively. We suggest that the multiblock copolymers form
      through collective H-bonding and hydrophobic interactions between the PAA and VG2
      peptide units, and that the unusual stability of the multiblock nanoparticles is
      conferred by the multiblock architecture. These hybrid multiblock copolymers are
      potentially useful as pH-responsive drug delivery vehicles, with the possibility
      of drug loading through concerted H-bonds and hydrophobic interactions.

PMID- 23976899
TI  - Preliminary Study of the Autism Self-Efficacy Scale for Teachers (ASSET).
AB  - The purpose of the current study was to evaluate a new measure, the Autism Self
      Efficacy Scale for Teachers (ASSET) for its dimensionality, internal consistency,
      and construct validity derived in a sample of special education teachers (N = 44)
      of students with autism. Results indicate that all items reflect one dominant
      factor, teachers' responses to items were internally consistent within the
      sample, and compared to a 100-point scale, a 6-point response scale is adequate.
      ASSET scores were found to be negatively correlated with scores on two subscale
      measures of teacher stress (i.e., self-doubt/need for support and disruption of
      the teaching process) but uncorrelated with teacher burnout scores. The ASSET is
      a promising tool that requires replication with larger samples.

PMID- 23976898
TI  - Ocular adnexal non-Hodgkin's lymphoma: a review of epidemiology and risk factors.
AB  - Ocular adnexal non-Hodgkin's lymphoma (NHL), the most common form of ophthalmic
      NHL, has a unique incidence pattern showing a steady and rapid increase in the
      past few decades, nearly equal rates among both genders, and predominance among
      Asians/Pacific Islanders. No major cause for ocular adnexal NHL has been
      identified, although infectious agents, immune disorders and genetic/epigenetic
      factors have all been implicated in its etiology. Identifying putative risk
      factors and biologic mechanisms leading to carcinogenesis in ocular adnexal NHL
      may enable implementation of effective preventive and/or therapeutic approaches
      for this malignancy. This article summarizes current knowledge on epidemiology of
      ocular adnexal NHL and the role of various potential risk factors in its
      etiology.

PMID- 23976900
TI  - Perforation of Meckel's diverticulum by a wood splinter in a 4-year-old child: a
      case report.
AB  - Perforation of Meckel's diverticulum by a foreign body represents an unusual and
      serious clinical occurrence. We present a case of a 4-year-old male who was
      admitted with symptoms of abdominal pain in the right iliac fossa, raising the
      suspicion of acute appendicitis. Exploratory laparotomy disclosed normal appendix
      and perforation of Meckel's diverticulum caused by a wood splinter. Meckel's
      diverticulectomy was performed and the child had an uneventful postoperative
      course. Preoperative diagnosis of perforated Meckel's diverticulum remains a
      challenging issue. Diagnosis should be considered in the presence of a right
      lower quadrant abdominal pain or a positive history of ingestion of a sharp
      foreign body. 

PMID- 23976903
TI  - Artifacts and essentialism.
AB  - Psychological essentialism is an intuitive folk belief positing that certain
      categories have a non-obvious inner "essence" that gives rise to observable
      features. Although this belief most commonly characterizes natural kind
      categories, I argue that psychological essentialism can also be extended in
      important ways to artifact concepts. Specifically, concepts of individual
      artifacts include the non-obvious feature of object history, which is evident
      when making judgments regarding authenticity and ownership. Classic examples
      include famous works of art (e.g., the Mona Lisa is authentic because of its
      provenance), but ordinary artifacts likewise receive value from their history
      (e.g., a worn and tattered blanket may have special value if it was one's
      childhood possession). Moreover, in some cases, object history may be thought to
      have causal effects on individual artifacts, much as an animal essence has causal
      effects. I review empirical support for these claims and consider the
      implications for both artifact concepts and essentialism. This perspective
      suggests that artifact concepts cannot be contained in a theoretical framework
      that focuses exclusively on similarity or even function. Furthermore, although
      there are significant differences between essentialism of natural kinds and
      essentialism of artifact individuals, the commonalities suggest that
      psychological essentialism may not derive from folk biology but instead may
      reflect more domain-general perspectives on the world.

PMID- 23976902
TI  - Mechanisms of hydrocephalus after neonatal and adult intraventricular hemorrhage.
AB  - Intraventricular hemorrhage (IVH) is a cause of significant morbidity and
      mortality and is an independent predictor of a worse outcome in intracerebral
      hemorrhage (ICH) and germinal matrix hemorrhage (GMH). IVH may result in both
      injuries to the brain as well as hydrocephalus. This paper reviews evidence on
      the mechanisms and potential treatments for IVH-induced hydrocephalus. One
      frequently cited theory to explain hydrocephalus after IVH involves obliteration
      of the arachnoid villi by microthrombi with subsequent inflammation and fibrosis
      causing CSF outflow obstruction. Although there is some evidence to support this
      theory, there may be other mechanisms involved, which contribute to the
      development of hydrocephalus. It is also unclear whether the causes of acute and
      chronic hydrocephalus after hemorrhage occur via different mechanisms; mechanical
      obstruction by blood in the former, and inflammation and fibrosis in the latter.
      Management of IVH and strategies for prevention of brain injury and hydrocephalus
      are areas requiring further study. A better understanding of the pathogenesis of
      hydrocephalus after IVH, may lead to improved strategies to prevent and treat
      post-hemorrhagic hydrocephalus. 

PMID- 23976904
TI  - The prognostic role of cancer stem cells in breast tumors.

PMID- 23976905
TI  - Physician-directed heart failure transitional care program: a retrospective case
      review.
AB  - BACKGROUND: Despite a variety of national efforts to improve transitions of care
      for patients at risk for rehospitalization, 30-day rehospitalization rates for
      patients with heart failure have remained largely unchanged. METHODS: This is a
      retrospective review of 73 patients enrolled in our hospital-based, physican
      directed Heart Failure Transitional Care Program (HFTCP). This study evaluated
      the 30- and 90- day readmission rates before and after enrollment in the program.
      The Transitionalist's services focused on bedside consultation prior to hospital
      discharge, follow-up home visits within 72 hours of discharge, frequent follow-up
      phone calls, disease-specific education, outpatient intravenous diuretic therapy,
      and around-the-clock telephone access to the Transitionalist. RESULTS: The pre
      enrollment 30-day readmission rates for acute decompensated heart failure (ADHF)
      and all-cause readmission was 26.0% and 28.8%, respectively, while the post
      enrollment rates for ADHF and all-cause readmission were 4.1% (P < 0.001) and
      8.2% (P = 0.002), respectively. The pre-enrollment 90-day all-cause and ADHF
      readmission rates were 69.8%, and 58.9% respectively, while the post-enrollment
      rates for all-cause and ADHF were 27.3% (P < 0.001) and 16.4% (P < 0.001)
      respectively. CONCLUSIONS: Our physician-implemented HFTCP reduced
      rehospitalization risk for patients enrolled in the program. This program may
      serve as a model to assist other hospital systems to reduce readmission rates of
      patients with HF.

PMID- 23976901
TI  - An Integrative Review of Mechanotransduction in Endothelial, Epithelial (Renal)
      and Dendritic Cells (Osteocytes).
AB  - In this review we will examine from a biomechanical and ultrastructural viewpoint
      how the cytoskeletal specialization of three basic cell types, endothelial cells
      (ECs), epithelial cells (renal tubule) and dendritic cells (osteocytes), enables
      the mechano-sensing of fluid flow in both their native in vivo environment and in
      culture, and the downstream signaling that is initiated at the molecular level in
      response to fluid flow. These cellular responses will be discussed in terms of
      basic mysteries and paradoxes encountered by each cell type. In ECs fluid shear
      stress (FSS) is nearly entirely attenuated by the endothelial glycocalyx that
      covers their apical membrane and yet FSS is communicated to both intracellular
      and junctional molecular components in activating a wide variety of signaling
      pathways. The same is true in proximal tubule (PT) cells where a dense brush
      border of microvilli covers the apical surface and the flow at the apical
      membrane is negligible. A four decade old unexplained mystery is the ability of
      PT epithelia to reliably reabsorb 60% of the flow entering the tubule regardless
      of the glomerular filtration rate. In the cortical collecting duct (CCD) the flow
      rates are so low that a special sensing apparatus, a primary cilia is needed to
      detect very small variations in tubular flow. In bone it has been a century old
      mystery as to how osteocytes embedded in a stiff mineralized tissue are able to
      sense miniscule whole tissue strains that are far smaller than the cellular level
      strains required to activate osteocytes in vitro.

PMID- 23976906
TI  - Factors influencing triage decisions in patients referred for ICU admission.
AB  - BACKGROUND: Few data is available on triage of critically ill patients. Because
      the demand for ICU beds often exceeds their availability, frequently intensivists
      need to triage these patients in order to equally and efficiently distribute the
      available resources based on the concept of potential benefit and reasonable
      chance of recovery. The objective of this study is to evaluate factors
      influencing triage decisions among patients referred for ICU admission and to
      assess its impact in outcome. METHODS: A single-center, prospective,
      observational study of 165 consecutive triage evaluations was conducted in
      patients referred for ICU admission that were either accepted, or refused and
      treated on the medical or surgical wards as well as the step-down and telemetry
      units. RESULTS: Seventy-one patients (43.0%) were accepted for ICU admission.
      Mean Acute Physiology and Chronic Health Evaluation (APACHE)-II score was 15.3 (0
      - 36) and 13.9 (0 - 30) for accepted and refused patients, respectively. Three
      patients (4.2%) had active advance directives on admission to ICU. Age, gender,
      and number of ICU beds available at the time of evaluation were not associated
      with triage decisions. Thirteen patients (18.3%) died in ICU, while the in
      hospital mortality for refused patients was 12.8%. CONCLUSION: Refusal of
      admission to ICU is common, although patients in which ICU admission is granted
      have higher mortality. Presence of active advance directives seems to play an
      important role in the triage decision process. Further efforts are needed to
      define which patients are most likely to benefit from ICU admission. Triage
      protocols or guidelines to promote efficient critical care beds use are
      warranted.

PMID- 23976907
TI  - Physician's Perceptions of Interprofessional Collaboration in Clinical Training
      Hospitals in Northeastern Japan.
AB  - BACKGROUND: Effective and efficient interprofessional collaboration (IPC) is
      needed between departments in a healthcare setting. Although Japanese physicians
      are expected to provide leadership in IPC, it has been suggested that their
      perception of IPC is more negative than among other healthcare professionals. The
      purpose of this study was to clarify Japanese physician's perceptions of IPC and
      what factors influenced their views. METHODS: This cross-sectional study surveyed
      732 medical doctors at a university hospital and six foundation hospitals in a
      prefecture located in Tohoku district, northeastern Japan. Those hospitals were
      approved for delivery of postgraduate clinical training. Physician's perceptions
      of IPC were investigated for three items, namely providing patient-centered care,
      preventing medical accidents, and improving the quality of medical care. A total
      of 409 doctors who were engaged in clinical practice, responded adequately to the
      survey. Factors associated with negative perceptions towards IPC among physicians
      were analyzed using a logistic regression model. RESULTS: The proportion of
      negative perceptions of IPC for providing patient-centered care, preventing
      medical accidents, and improving the quality of medical care were 41.1%, 34.0%
      and 33.7%, respectively. Negative perceptions of IPC for providing patient
      centered care were associated with older age (50 + years; odds ratio (OR): 2.73;
      95% confidence interval (CI): 1.11 - 6.68) and a lower frequency of
      interprofessional meetings (no meetings; OR: 2.95; 95%CI: 1.43 - 6.08). Negative
      perceptions of IPC for preventing medical accidents were associated with a lower
      frequency of interprofessional meetings (no meetings, OR: 3.23; 95%CI: 1.58 -
      6.62). Negative perceptions of IPC for improving the quality of medical care were
      associated with middle age (40 - 49 years, OR: 2.93; 95%CI: 1.20 - 7.12) and a
      lower frequency of interprofessional meetings (no meetings; OR: 2.75; 95%CI: 1.34
      - 5.66). CONCLUSIONS: Physician's negative perceptions of IPC in our study were
      associated with age and a lower frequency of interprofessional meetings. Our
      findings suggest that effective regular interprofessional meetings serve to share
      information about patients, and to allow physicians to understand each other
      better, which should have a positive impact on the quality of patient-centered
      care.

PMID- 23976908
TI  - Opiate dependence as an independent and interactive risk factor for arterial
      stiffness and cardiovascular ageing - a longitudinal study in females.
AB  - BACKGROUND: Despite intriguing observational cross-sectional data there are no
      longitudinal studies of opiate related arterial disease. As opiates act via
      P16INK4A/CDKN2A, and vascular ageing has been thought to be a surrogate for
      organismal ageing, the subject has far-reaching implications. METHODS: Pulse Wave
      Analysis (PWA) by radial arterial tonometry (SphygmoCor) was performed on control
      and opiate dependent patients. RESULTS: A total of 37 controls were compared with
      93 opiate dependents. They were studied on 117 and 275 occasions respectively up
      to 1,797 days. The mean (+/- S.E.M.) ages were 38.72 +/- 2.64 and 33.78 +/- 0.90
      years (P = 0.0260), 91.4% and 10.8% smoked (P < 0.0001). Body mass index rose
      more in controls (P = 0.0185) and in interaction with time (P = 0.0025). When
      controlled for time and BMI, opiate dependency status was shown to be associated
      with vascular age and central arterial stiffness and pressure indices (all P <
      0.05). When repeated measures multiple regression was performed on all
      traditional cardiovascular risk factors, the opiate dose-duration interaction was
      significant and appeared in 12 terms in the final model. It was also
      independently significant (P = 0.0153). Opiate dose or duration appeared in a
      further 15 terms. The model was shown to be significantly improved by the
      inclusion of terms for opiate dependency (A.I.C. 71.10 v 54.31, P < 0.0001).
      CONCLUSION: These data confirm increased vascular stiffness and ageing in a
      longitudinal study, and thereby imply advanced organismal ageing. These
      multivariate studies are consistent with opiate dependency as an interactive and
      multivariate cardiovascular risk factor and emphasize the role of treatment
      duration.

PMID- 23976909
TI  - Effect of Caloric Intake 25 or 30 kcal/kg/day on the Glycemic Control in Obese
      Patients With Type 2 Diabetes.
AB  - BACKGROUND: The recommended total dietary energy intake prescribed medical
      nutrition therapy for obese or overweight patients with type 2 diabetes in Japan
      is often set at 25 kcal/kg ideal body weight (IBW)/day. This study was conducted
      to determine the impact of the total dietary energy intake (25 or 30 kcal/kg
      IBW/day) on the glycemic control, lipid profile, and satisfaction level in
      overweight patients with type 2 diabetes. METHODS: We performed interview and a
      designed prospective, randomized, controlled, multicenter study trial.
      Recruitment for interview for doctors and hospitalization of the obese or
      overweight patients with type 2 diabetes began from September 2008 and continued
      until June 2010. The subjects were randomly assigned to 25 kcal/kg IBW/day group
      (25 kcal group) or 30 kcal/kg IBW/day group (30 kcal group). The primary endpoint
      was the body weight of the subjects at the time of hospitalization, at the time
      of discharge from the hospital, and at 3, 6 and 12 months after discharge from
      the hospital. RESULTS: The glycemic control, lipid control and body weight were
      similar between the 25 and 30 kcal groups during the 12-month follow-up, and the
      degree of satisfaction in respect of the medical treatment was significantly
      higher in the 30 kcal group than in the 25 kcal group at 1 year after discharge.
      CONCLUSIONS: It is considered to be preferable for the caloric intake to be set
      at 30kcal/kg IBW/day rather than at 25 kcal/kg IBW/day for obese or overweight
      patients with type 2 diabetes.

PMID- 23976910
TI  - Predictors of severity of alcohol withdrawal in hospitalized patients.
AB  - BACKGROUND: Alcohol withdrawal is a relatively common problem among chronic
      alcohol users, and its severity will determine the setting in which it will be
      more appropriate to take care of the patients. Those with mild symptoms will be
      managed in an outpatient setting, as opposed to those with advanced moderate or
      severe symptoms who will require inpatient management. Among those patients who
      will require hospitalization, some of them will do well in a regular floor, but
      some of them will have to be managed in an intensive care unit. We tried to
      determine whether some variables could be predictive of an increased risk of
      being managed in an intensive care unit as opposed to being managed in a regular
      medical floor. METHODS: A retrospective non-randomized review trial design was
      implemented and a total of 110 medical charts of patients admitted to our
      institution with severe alcohol withdrawal during the calendar year of 2009 were
      reviewed. Different demographic and clinical parameters were analyzed, and their
      significance established in regard to the clinical settings (ICU vs. medical
      floor) in which the patients were managed. RESULTS: The patients managed in the
      ICU were found to be younger than their counterparts who were managed in the
      medical floor, and they were more likely to be white and unemployed. On the other
      hand, being diabetic, using over-the-counter drugs or prescribed medications
      appeared to be protective factors, resulting in management of alcohol withdrawal
      on the medical floors. CONCLUSION: A likely explanation to our findings could be
      that patients exhibiting better health protective behaviors have a better chance
      to stay away from the ICU. However no tools could be developed to stratify the
      patients' risks and more behavioral and observational cohort studies will be
      needed for that purpose.

PMID- 23976911
TI  - Risk Factors That can Predict Antenatal Insulin Need in Gestational Diabetes.
AB  - BACKGROUND: This study was undertaken to assess the association between insulin
      need in gestational diabetes mellitus (GDM) and clinical features and laboratory
      parameters. Factors that can predict insulin need are also identified. METHODS:
      Cases with GDM were included retrospectively from records. Cases which failed to
      achieve target blood glucose levels with medical nutrition therapy (MNT) and need
      insulin treatment were recorded. Risk factors which can predict antenatal insulin
      treatment (AIT) were identified as follows; the presence of diabetes in a first
      degree relative, body mass index prior to pregnancy, number of parity, history of
      GDM, macrosomic baby delivery (> 4,000 g), age, gestational week at time of
      diagnosis, body mass index during diagnosis, weight gain untill diagnosis, mean
      systolic and diastolic blood pressure, HbA1C level during diagnosis, and fasting
      plasma glucose on diagnostic oral glucose tolerance test. Presence of a
      statistical significance between those patient features and AIT was assessed.
      Independent predictors for AIT were evaluated. RESULTS: A total of 300 cases were
      recruited from records, 190 cases (63.3%) were followed only with MNT until
      delivery and 110 cases (36.7%) were initiated AIT. The association between AIT
      and patient factors like presence of diabetes in the pedigree, week of gestation
      at which GDM was diagnosed, BMI during diagnosis, HbA1C levels, and fasting
      plasma glucose during diagnosis was found (P = 0.03; 0.008; 0.049; 0.001 and
      0.001respectively). Multivariant analysis showed that fasting plasma glucose
      levels during diagnosis and HbA1C levels were independent risk factors for AIT.
      Fasting plasma glucose values that can predict AIT were identified > 89.5 mg/dL
      with 72.7% sensitivity and 62.6% spesifity (P < 0.001). Positive predictive value
      was 73% (P < 0.001). Also, HbA1C levels that can predict AIT was found to be >
      5.485% with 65.3% sensitivity and 66.7% spesifitiy(P < 0.001) with a positive
      predictive value 68% (P < 0.001). CONCLUSIONS: Independent predictors for AIT
      were found as fasting plasma glucose on OGTT and HbA1c levels during diagnosis in
      GDM. Cases with fasting plasma glucose >= 89.5 mg/dL or HbA1C >= 5.485% should be
      closely followed for AIT in specified centers.

PMID- 23976912
TI  - Antimicrobial activity of common mouthwash solutions on multidrug-resistance
      bacterial biofilms.
AB  - BACKGROUND: Periodontal bacteria occur in both planktonic and biofilm forms.
      While poor oral hygiene leads to accumulation of bacteria, reducing these
      microbes is the first step toward good oral hygiene. This is usually achieved
      through the use of mouthwash solutions. However, the exact antibacterial activity
      of mouthwash solution, especially when bacteria form biofilms, is yet to be
      determined. In this study, we evaluated the antibacterial activity of common
      mouthwash solutions against standard bacteria in their planktonic and biofilm
      states. METHODS: Standard bacterial strains were cultured, and biofilm were
      formrd. Thereafter, using standard method for determination of minimum inhibitory
      concentrations (MIC) values of various mouthwash solutions were determined.
      RESULTS: Results show that common mouthwash solutions have variable antibacterial
      activity depending on their major active components. Only mouthwash solutions
      containing chlorohexidine gluconate or cetylpyridinum chloride exhibited activity
      against majority, but not all tested bacterial strains in their biofilm state.
      Additionally, bacteria are generally less susceptible to all mouthwash solutions
      in their biofilm as compared to planktonic state. CONCLUSIONS: While mouthwash
      solutions have variable antibacterial activity, bacteria in their biofilm state
      pose a challenge to dental hygiene/care where bacteria become not susceptible to
      majority of available mouthwash solutions.

PMID- 23976913
TI  - Evaluation of risk factors for recurrent wheezing episodes.
AB  - BACKGROUND: We aimed to evaluate the risk factors for recurrent wheezing in
      patients diagnosed with acute bronchiolitis. METHOD: From 2009 to 2011, 500
      patients from the pediatric clinics, with first attack of acute bronchiolitis
      were included in this prospective study. Each patient's age, gender, birth
      weight, duration of breastfeeding, family history of atopy and asthma, smoking
      exposure, source of heating in the house, the presence of pets, any history of
      chronic disease have been questioned. The patients were followed for a duration
      of 12 - 24 months. RESULTS: In this study, 39% (n = 195) of the cases were female
      and 61% (n = 305) were male, with a median age of 3 months old. Male gender, low
      birth weight (< 2,500 g), low gestational age (< 37 weeks), breastfeeding of less
      than 6 months, congenital heart disease, family history of atopy, asthma, smoking
      exposure, stove warming, was found as significant risk factors for recurrent
      wheezing, however, presence of pets at home was found to be a protective factor.
      CONCLUSIONS: Informing parents about the risk factors such as exposure to
      cigarette smoke, heating mode, duration of breastfeeding can significantly
      decrease recurrent episodes of wheezing.

PMID- 23976914
TI  - Participant preferences for the provision of registration trials results.
AB  - BACKGROUND: Clinical trials leading to drug approval (registration trials) play a
      central role in the drug development process, and attention has recently been
      paid to providing trial results to participants. In the present study, we
      examined the preferences of participants of registration trials for the provision
      of trial-related information. METHODS: We used questionnaires to survey the
      preferences of registration trial participants at Tokushima University Hospital
      and Tokushima National Hospital. Of the 15 questions, 6 related to participant
      characteristics and the trials in which they participated, while 9 questions were
      concerned with preferences for the provision of information. A five-point scale
      (strongly agree, agree, neutral, disagree, and strongly disagree) was used, and
      positive answers (strongly agree and agree) were considered to indicate a
      positive preference. RESULTS: Of the 58 subjects, 1 declined, giving a response
      rate of 98%. More than 70% of participants preferred to obtain information, even
      if they had served as controls. More than 80% of participants agreed to obtain
      information relating to trial results, even if the results were negative, and
      more than 80% of participants agreed to obtain information on the labeling state
      of the agent, even if development had ceased. Although more than 60% of
      participants agreed for the provision of information on their allocation and
      around more than 70% agreed to the provision of information on registration
      trials status, significantly fewer participants with difficult-to-treat diseases
      (for example, neurological and malignant diseases) agreed to obtain information
      compared with participants with other types of diseases (for example, acute,
      chronic, and psychological diseases). More than 50% of participants desired
      information to be provided directly by the physician, while a considerable number
      of participants desired information by means of clinical research coordinators
      (CRCs) (24.4%) or by posted letter (33.3%). CONCLUSION: The present results
      suggest the preferences for the provision of individual and overall information
      concerning research results. However, further study is warranted to determine
      participant preferences more precisely and the effect of the CRC-initiated
      infrastructure for providing information on patient satisfaction and for
      promoting registration trials.

PMID- 23976920
TI  - Detection of DNA from Leishmania (Viannia): accuracy of polymerase chain reaction
      for the diagnosis of cutaneous leishmaniasis.
AB  - Cutaneous leishmaniasis (CL) can occur in skin and mucosa, causing disfiguring
      lesions. The laboratory diagnosis of CL involves immunological methods and
      optical detection of the parasite, al of which have limitations. There is a need
      for more effective diagnostic methods for CL which wil allow treatment to be
      initiated more promptly in order to help prevent the development of severe forms
      of mucosal disease, and to estimate the prognosis of the infection. The
      polymerase chain reaction (PCR) has been widely used to diagnose CL, because of
      its higher sensitivity. This study estimated the accuracy and compared PCRs of
      samples from lesion scarification (PCR-L) and blood sample-enriched leukocytes
      (PCR-B) with three conventional diagnostic techniques: parasite direct search
      (DS), Montenegro skin test (MST), and indirect immunofluorescence reaction (IIF).
      The study included 276 patients under suspicion of CL. We conducted a cross
      sectional study, in which patients were selected by convenience sampling. We used
      MP3H/MP1L primers to generate a Leishmania (Viannia) (minicircle kDNA) fragment
      of 70-bp. Of 106 patients with CL, 83.87%, 51.67%, 64.52%, 85.71%, or 96.10%
      tested positive by PCR-L, PCR-B, DS, IIF, or MST, respectively. Five patients
      tested positive only by PCR-L, and two other patients only by PCR-B. PCR-L is
      indicated for use in patients with chronic lesions or Leishmania reinfection,
      which may progress to mucosal lesion. PCR-B is indicated for use in patients with
      negative results in conventional tests or for patients with no apparent lesion.
      PCR is not only useful in diagnosing CL but also helps to identify the infecting
      species. 

PMID- 23976921
TI  - Antagonistic regulation of flowering time through distinct regulatory subunits of
      protein phosphatase 2A.
AB  - Protein phosphatase 2A (PP2A) consists of three types of subunits: a catalytic
      (C), a scaffolding (A), and a regulatory (B) subunit. In Arabidopsis thaliana and
      other organisms the regulatory B subunits are divided into at least three non
      related groups, B55, B' and B". Flowering time in plants mutated in B55 or B'
      genes were investigated in this work. The PP2A-b55alpha and PP2A-b55beta
      (knockout) lines showed earlier flowering than WT, whereas a PP2A-b'gamma
      (knockdown) line showed late flowering. Average advancements of flowering in PP2A
      b55 mutants were 3.4 days in continuous light, 6.6 days in 12 h days, and 8.2
      days in 8 h days. Average delays in the PP2A-b'gamma mutant line were 7.1 days in
      16 h days and 4.7 days in 8 h days. Expression of marker genes of genetically
      distinct flowering pathways (CO, FLC, MYB33, SPL3), and the floral integrator
      (FT, SOC1) were tested in WT, pp2a mutants, and two known flowering time mutants
      elf6 and edm2. The results are compatible with B55 acting at and/or downstream of
      the floral integrator, in a non-identified pathway. B' gamma was involved in
      repression of FLC, the main flowering repressor gene. For B'gamma the results are
      consistent with the subunit being a component in the major autonomous flowering
      pathway. In conclusion PP2A is both a positive and negative regulator of
      flowering time, depending on the type of regulatory subunit involved. 

PMID- 23976922
TI  - Disruption of hydrogen bonds between major histocompatibility complex class II
      and the peptide N-terminus is not sufficient to form a human leukocyte antigen-DM
      receptive state of major histocompatibility complex class II.
AB  - Peptide presentation by MHC class II is of critical importance to the function of
      CD4+ T cells. HLA-DM resides in the endosomal pathway and edits the peptide
      repertoire of newly synthesized MHC class II molecules before they are exported
      to the cell surface. HLA-DM ensures MHC class II molecules bind high affinity
      peptides by targeting unstable MHC class II:peptide complexes for peptide
      exchange. Research over the past decade has implicated the peptide N-terminus in
      modulating the ability of HLA-DM to target a given MHC class II:peptide
      combination. In particular, attention has been focused on both the hydrogen bonds
      between MHC class II and peptide, and the occupancy of the P1 anchor pocket. We
      sought to solve the crystal structure of a HLA-DR1 molecule containing a
      truncated hemagglutinin peptide missing three N-terminal residues compared to the
      full-length sequence (residues 306-318) to determine the nature of the MHC class
      II:peptide species that binds HLA-DM. Here we present structural evidence that
      HLA-DR1 that is loaded with a peptide truncated to the P1 anchor residue such
      that it cannot make select hydrogen bonds with the peptide N-terminus, adopts the
      same conformation as molecules loaded with full-length peptide. HLA-DR1:peptide
      combinations that were unable to engage up to four key hydrogen bonds were also
      unable to bind HLA-DM, while those truncated to the P2 residue bound well. These
      results indicate that the conformational changes in MHC class II molecules that
      are recognized by HLA-DM occur after disengagement of the P1 anchor residue. 

PMID- 23976923
TI  - Association of neighbourhood and individual social capital, neighbourhood
      economic deprivation and self-rated health in South Africa--a multi-level
      analysis.
AB  - INTRODUCTION: Social capital is said to influence health, mostly in research
      undertaken in high income countries' settings. Because social capital may differ
      from one setting to another, it is suggested that its measurement be context
      specific. We examine the association of individual and neighbourhood level social
      capital, and neighbourhood deprivation to self-rated health using a multi-level
      analysis. METHODS: Data are taken from the 2008 South Africa National Income
      Dynamic Survey. Health was self-reported on a scale from 1 (excellent) to 5
      (poor). Two measures of social capital were used: individual, measured by two
      variables denoting trust and civic participation; and neighbourhood social
      capital, denoting support, association, behaviour and safety in a community.
      RESULTS: Compared to males, females were less likely to report good health (Odds
      Ratio 0.82: Confidence Interval 0.73, 0.91). There were variations in association
      of individual social capital and self-rated health among the provinces. In
      Western Cape (1.37: 0.98, 1.91) and North West (1.39: 1.13, 1.71), trust was
      positively associated with reporting good health, while the reverse was true in
      Limpopo (0.56: 0.38, 0.84) and Free State (0.70: 0.48, 1.02). In Western Cape
      (0.60: 0.44, 0.82) and Mpumalanga (0.72: 0.55, 0.94), neighbourhood social
      capital was negatively associated with reporting good health. In North West
      (1.59: 1.27, 1.99) and Gauteng (1.90: 1.21, 2.97), increased neighbourhood social
      capital was positively associated with reporting good health. CONCLUSION: Our
      study demonstrated the importance of considering contextual factors when
      analysing the relationship between social capital and health. Analysis by
      province showed variations in the way in which social capital affected health in
      different contexts. Further studies should be undertaken to understand the
      mechanisms through which social capital impacts on health in South Africa.

PMID- 23976938
TI  - Psychedelics and mental health: a population study.
AB  - BACKGROUND: The classical serotonergic psychedelics LSD, psilocybin, mescaline
      are not known to cause brain damage and are regarded as non-addictive. Clinical
      studies do not suggest that psychedelics cause long-term mental health problems.
      Psychedelics have been used in the Americas for thousands of years. Over 30
      million people currently living in the US have used LSD, psilocybin, or
      mescaline. OBJECTIVE: To evaluate the association between the lifetime use of
      psychedelics and current mental health in the adult population. METHOD: Data
      drawn from years 2001 to 2004 of the National Survey on Drug Use and Health
      consisted of 130,152 respondents, randomly selected to be representative of the
      adult population in the United States. Standardized screening measures for past
      year mental health included serious psychological distress (K6 scale), mental
      health treatment (inpatient, outpatient, medication, needed but did not receive),
      symptoms of eight psychiatric disorders (panic disorder, major depressive
      episode, mania, social phobia, general anxiety disorder, agoraphobia,
      posttraumatic stress disorder, and non-affective psychosis), and seven specific
      symptoms of non-affective psychosis. We calculated weighted odds ratios by
      multivariate logistic regression controlling for a range of sociodemographic
      variables, use of illicit drugs, risk taking behavior, and exposure to traumatic
      events. RESULTS: 21,967 respondents (13.4% weighted) reported lifetime
      psychedelic use. There were no significant associations between lifetime use of
      any psychedelics, lifetime use of specific psychedelics (LSD, psilocybin,
      mescaline, peyote), or past year use of LSD and increased rate of any of the
      mental health outcomes. Rather, in several cases psychedelic use was associated
      with lower rate of mental health problems. CONCLUSION: We did not find use of
      psychedelics to be an independent risk factor for mental health problems.

PMID- 23976939
TI  - Modeling the non-stationary climate dependent temporal dynamics of Aedes aegypti.
AB  - BACKGROUND: Temperature and humidity strongly affect the physiology, longevity,
      fecundity and dispersal behavior of Aedes aegypti, vector of dengue fever.
      Contrastingly, the statistical associations measured between time series of
      mosquito abundance and meteorological variables are often weak and contradictory.
      Here, we investigated the significance of these relationships at different time
      scales. METHODS AND FINDINGS: A time series of the adult mosquito abundance from
      a medium-sized city in Brazil, lasting 109 weeks was analyzed. Meteorological
      variables included temperature, precipitation, wind velocity and humidity. As
      analytical tools, generalized linear models (GLM) with time lags and interaction
      terms were used to identify average effects while the wavelet analysis was
      complementarily used to identify transient associations. The fitted GLM showed
      that mosquito abundance is significantly affected by the interaction between
      lagged temperature and humidity, and also by the mosquito abundance a week
      earlier. Extreme meteorological variables were the best predictors, and the
      mosquito population tended to increase at values above [Formula: see text] and
      54% humidity. The wavelet analysis identified non-stationary local effects of
      these meteorological variables on abundance throughout the study period, with
      peaks in the spring-summer period. The wavelet detected weak but significant
      effects for precipitation and wind velocity. CONCLUSION: Our results support the
      presence of transient relationships between meteorological variables and mosquito
      abundance. Such transient association may be explained by the ability of Ae.
      aegypti to buffer part of its response to climate, for example, by choosing sites
      with proper microclimate. We also observed enough coupling between the abundance
      and meteorological variables to develop a model with good predictive power.
      Extreme values of meteorological variables with time lags, interaction terms and
      previous mosquito abundance are strong predictors and should be considered when
      understanding the climate effect on mosquito abundance and population growth.

PMID- 23976940
TI  - Habitat use by fishes in coral reefs, seagrass beds and mangrove habitats in the
      Philippines.
AB  - Understanding the interconnectivity of organisms among different habitats is a
      key requirement for generating effective management plans in coastal ecosystems,
      particularly when determining component habitat structures in marine protected
      areas. To elucidate the patterns of habitat use by fishes among coral, seagrass,
      and mangrove habitats, and between natural and transplanted mangroves, visual
      censuses were conducted semiannually at two sites in the Philippines during
      September and March 2010-2012. In total, 265 species and 15,930 individuals were
      recorded. Species richness and abundance of fishes were significantly higher in
      coral reefs (234 species, 12,306 individuals) than in seagrass (38 species, 1,198
      individuals) and mangrove (47 species, 2,426 individuals) habitats. Similarity
      tests revealed a highly significant difference among the three habitats. Fishes
      exhibited two different strategies for habitat use, inhabiting either a single
      (85.6% of recorded species) or several habitats (14.4%). Some fish that utilized
      multiple habitats, such as Lutjanus monostigma and Parupeneus barberinus, showed
      possible ontogenetic habitat shifts from mangroves and/or seagrass habitats to
      coral reefs. Moreover, over 20% of commercial fish species used multiple
      habitats, highlighting the importance of including different habitat types within
      marine protected areas to achieve efficient and effective resource management.
      Neither species richness nor abundance of fishes significantly differed between
      natural and transplanted mangroves. In addition, 14 fish species were recorded in
      a 20-year-old transplanted mangrove area, and over 90% of these species used
      multiple habitats, further demonstrating the key role of transplanted mangroves
      as a reef fish habitat in this region. 

PMID- 23976941
TI  - Infection frequency of hepatitis C virus and IL28B haplotypes in Papua New
      Guinea, Fiji, and Kiribati.
AB  - It has been estimated that there are more than 60 million Hepatitis C virus (HCV)
      carriers in the World Health Organisation's Western Pacific region (WHO-WPR),
      where liver cancer is among the top three causes of cancer death. WHO and the US
      Centres for Disease Control and Prevention report the prevalence of HCV in the
      South Pacific islands (countries within the WHO-WPR) to be high (5-10% and >2%
      respectively). However, since HCV is not tested for in many of these countries,
      there is sparse data available to support this assertion. We screened ~2000
      apparently healthy individuals from Papua New Guinea, Fiji and Kiribati and found
      a sero-prevalence of 2.0%, 0.1% and 0%, respectively. All sero-positive samples
      tested negative for HCV RNA. Curious as to why all the sero-positive individuals
      were negative for HCV-RNA, we also screened them for the HCV protective IL28B SNP
      markers rs12979860 and rs8099917. All antibody-positive participants bar one had
      HCV protective haplotypes. Our results suggest that HCV is present in these
      Pacific island countries, albeit at a prevalence lower than previous estimates.
      As none of our participants had undergone antiviral treatment, and therefore must
      have cleared infection naturally, we hypothesise that genotypes 1 and/or 4 are
      circulating in South Pacific Island people and that these peoples are genetically
      predisposed to be more likely to spontaneous resolve HCV infection than to become
      chronic carriers. 

PMID- 23976942
TI  - Assessing interactions between common genetic variant on 2q35 and hormone
      receptor status with breast cancer risk: evidence based on 26 studies.
AB  - Genome-wide association studies have identified 2q35-rs13387042 as a new breast
      cancer (BC) susceptibility locus in populations of European descent. Since then,
      the relationship between 2q35-rs13387042 and breast cancer has been reported in
      various ethnic groups; however, these studies have yielded inconsistent results.
      To investigate this inconsistency, we performed a meta-analysis of 26 studies
      involving a total of 101,529 cases and 167,363 controls for 2q35-rs13387042
      polymorphism to evaluate its effect on genetic susceptibility for breast cancer.
      An overall random effects odds ratio of 1.14 (95% CI: 1.11-1.16, P<10-5) was
      found for rs13387042-A variant. Significant results were also observed using
      dominant (OR = 1.14, 95% CI: 1.12-1.17, P<10-5), recessive (OR = 1.17, 95% CI:
      1.13-1.21, P<10-5) and co-dominant genetic model (heterozygous: OR = 1.15, 95%
      CI: 1.12-1.19, P<10-5; homozygous: OR = 1.20, 95% CI: 1.15-1.24, P<10-5). There
      was strong evidence of heterogeneity, which largely disappeared after
      stratification by ethnicity. Significant associations were found in East Asians,
      and White populations when stratified by ethnicity; while no significant
      associations were observed in Africans and other ethnic populations. An
      association was observed for both ER-positive (OR = 1.17, 95% 1.15-1.19; P<10-5)
      and ER-negative disease (OR = 1.08, 95% CI: 1.04-1.13; P<10-4) and both
      progesterone receptor (PR)-positive (OR = 1.18, 95% CI: 1.15-1.21; P<10-5) and PR
      negative disease (OR = 1.10, 95% CI: 1.05-1.15; P<10-4). In conclusion, this meta
      analysis demonstrated that the A allele of 2q35-rs13387042 is a risk factor
      associated with increased breast cancer susceptibility.

PMID- 23976943
TI  - Transport inhibition of digoxin using several common P-gp expressing cell lines
      is not necessarily reporting only on inhibitor binding to P-gp.
AB  - We have reported that the P-gp substrate digoxin required basolateral and apical
      uptake transport in excess of that allowed by digoxin passive permeability (as
      measured in the presence of GF120918) to achieve the observed efflux kinetics
      across MDCK-MDR1-NKI (The Netherlands Cancer Institute) confluent cell
      monolayers. That is, GF120918 inhibitable uptake transport was kinetically
      required. Therefore, IC50 measurements using digoxin as a probe substrate in this
      cell line could be due to inhibition of P-gp, of digoxin uptake transport, or
      both. This kinetic analysis is now extended to include three additional cell
      lines: MDCK-MDR1-NIH (National Institute of Health), Caco-2 and CPT-B2 (Caco-2
      cells with BCRP knockdown). These cells similarly exhibit GF120918 inhibitable
      uptake transport of digoxin. We demonstrate that inhibition of digoxin transport
      across these cell lines by GF120918, cyclosporine, ketoconazole and verapamil is
      greater than can be explained by inhibition of P-gp alone. We examined three
      hypotheses for this non-P-gp inhibition. The inhibitors can: (1) bind to a
      basolateral digoxin uptake transporter, thereby inhibiting digoxin's cellular
      uptake; (2) partition into the basolateral membrane and directly reduce membrane
      permeability; (3) aggregate with digoxin in the donor chamber, thereby reducing
      the free concentration of digoxin, with concomitant reduction in digoxin uptake.
      Data and simulations show that hypothesis 1 was found to be uniformly acceptable.
      Hypothesis 2 was found to be uniformly unlikely. Hypothesis 3 was unlikely for
      GF120918 and cyclosporine, but further studies are needed to completely
      adjudicate whether hetero-dimerization contributes to the non-P-gp inhibition for
      ketoconazole and verapamil. We also find that P-gp substrates with relatively low
      passive permeability such as digoxin, loperamide and vinblastine kinetically
      require basolateral uptake transport over that allowed by +GF120918 passive
      permeability, while highly permeable P-gp substrates such as amprenavir,
      quinidine, ketoconazole and verapamil do not, regardless of whether they actually
      use the basolateral transporter. 

PMID- 23976944
TI  - Automatic prediction of rheumatoid arthritis disease activity from the electronic
      medical records.
AB  - OBJECTIVE: We aimed to mine the data in the Electronic Medical Record to
      automatically discover patients' Rheumatoid Arthritis disease activity at
      discrete rheumatology clinic visits. We cast the problem as a document
      classification task where the feature space includes concepts from the clinical
      narrative and lab values as stored in the Electronic Medical Record. MATERIALS
      AND METHODS: The Training Set consisted of 2792 clinical notes and associated lab
      values. Test Set 1 included 1749 clinical notes and associated lab values. Test
      Set 2 included 344 clinical notes for which there were no associated lab values.
      The Apache clinical Text Analysis and Knowledge Extraction System was used to
      analyze the text and transform it into informative features to be combined with
      relevant lab values. RESULTS: Experiments over a range of machine learning
      algorithms and features were conducted. The best performing combination was
      linear kernel Support Vector Machines with Unified Medical Language System
      Concept Unique Identifier features with feature selection and lab values. The
      Area Under the Receiver Operating Characteristic Curve (AUC) is 0.831 (sigma =
      0.0317), statistically significant as compared to two baselines (AUC = 0.758,
      sigma = 0.0291). Algorithms demonstrated superior performance on cases clinically
      defined as extreme categories of disease activity (Remission and High) compared
      to those defined as intermediate categories (Moderate and Low) and included
      laboratory data on inflammatory markers. CONCLUSION: Automatic Rheumatoid
      Arthritis disease activity discovery from Electronic Medical Record data is a
      learnable task approximating human performance. As a result, this approach might
      have several research applications, such as the identification of patients for
      genome-wide pharmacogenetic studies that require large sample sizes with precise
      definitions of disease activity and response to therapies.

PMID- 23976946
TI  - In-lake processes offset increased terrestrial inputs of dissolved organic carbon
      and color to lakes.
AB  - Increased color in surface waters, or browning, can alter lake ecological
      function, lake thermal stratification and pose difficulties for drinking water
      treatment. Mechanisms suggested to cause browning include increased dissolved
      organic carbon (DOC) and iron concentrations, as well as a shift to more colored
      DOC. While browning of surface waters is widespread and well documented, little
      is known about why some lakes resist it. Here, we present a comprehensive study
      of Malaren, the third largest lake in Sweden. In Malaren, the vast majority of
      water and DOC enters a western lake basin, and after approximately 2.8 years,
      drains from an eastern basin. Despite 40 years of increased terrestrial inputs of
      colored substances to western lake basins, the eastern basin has resisted
      browning over this time period. Here we find the half-life of iron was far
      shorter (0.6 years) than colored organic matter (A420; 1.7 years) and DOC as a
      whole (6.1 years). We found changes in filtered iron concentrations relate
      strongly to the observed loss of color in the western basins. In addition, we
      observed a substantial shift from colored DOC of terrestrial origin, to less
      colored autochthonous sources, with a substantial decrease in aromaticity (-17%)
      across the lake. We suggest that rapid losses of iron and colored DOC caused the
      limited browning observed in eastern lake basins. Across a wider dataset of 69
      Swedish lakes, we observed greatest browning in acidic lakes with shorter
      retention times (< 1.5 years). These findings suggest that water residence time,
      along with iron, pH and colored DOC may be of central importance when modeling
      and projecting changes in brownification on broader spatial scales.

PMID- 23976945
TI  - Disruption of basal lamina components in neuromotor synapses of children with
      spastic quadriplegic cerebral palsy.
AB  - Cerebral palsy (CP) is a static encephalopathy occurring when a lesion to the
      developing brain results in disordered movement and posture. Patients present
      with sometimes overlapping spastic, athetoid/dyskinetic, and ataxic symptoms.
      Spastic CP, which is characterized by stiff muscles, weakness, and poor motor
      control, accounts for ~80% of cases. The detailed mechanisms leading to
      disordered movement in spastic CP are not completely understood, but clinical
      experience and recent studies suggest involvement of peripheral motor synapses.
      For example, it is recognized that CP patients have altered sensitivities to
      drugs that target neuromuscular junctions (NMJs), and protein localization
      studies suggest that NMJ microanatomy is disrupted in CP. Since CP originates
      during maturation, we hypothesized that NMJ disruption in spastic CP is
      associated with retention of an immature neuromotor phenotype later in life.
      Scoliosis patients with spastic CP or idiopathic disease were enrolled in a
      prospective, partially-blinded study to evaluate NMJ organization and neuromotor
      maturation. The localization of synaptic acetylcholine esterase (AChE) relative
      to postsynaptic acetylcholine receptor (AChR), synaptic laminin beta2, and
      presynaptic vesicle protein 2 (SV2) appeared mismatched in the CP samples;
      whereas, no significant disruption was found between AChR and SV2. These data
      suggest that pre- and postsynaptic NMJ components in CP children were
      appropriately distributed even though AChE and laminin beta2 within the synaptic
      basal lamina appeared disrupted. Follow up electron microscopy indicated that
      NMJs from CP patients appeared generally mature and similar to controls with some
      differences present, including deeper postsynaptic folds and reduced presynaptic
      mitochondria. Analysis of maturational markers, including myosin, syntrophin,
      myogenin, and AChR subunit expression, and telomere lengths, all indicated
      similar levels of motor maturation in the two groups. Thus, NMJ disruption in CP
      was found to principally involve components of the synaptic basal lamina and
      subtle ultra-structural modifications but appeared unrelated to neuromotor
      maturational status. 

PMID- 23976947
TI  - Ex vivo analysis of human memory B lymphocytes specific for A and B influenza
      hemagglutinin by polychromatic flow-cytometry.
AB  - Understanding the impact that human memory B-cells (MBC), primed by previous
      infections or vaccination, exert on neutralizing antibody responses against
      drifted influenza hemagglutinin (HA) is key to design best protective vaccines. A
      major obstacle to these studies is the lack of practical tools to analyze HA
      specific MBCs in human PBMCs ex vivo. We report here an efficient method to
      identify MBCs carrying HA-specific BCR in frozen PBMC samples. By using
      fluorochrome-tagged recombinant HA baits, and vaccine antigens from mismatched
      influenza strains to block BCR-independent binding, we developed a protocol
      suitable for quantitative, functional and molecular analysis of single MBCs
      specific for HA from up to two different influenza strains in the same tube. This
      approach will permit to identify the naive and MBC precursors of plasmablasts and
      novel MBCs appearing in the blood following infection or vaccination, thus
      clarifying the actual contribution of pre-existing MBCs in antibody responses
      against novel influenza viruses. Finally, this protocol can allow applying high
      throughput deep sequencing to analyze changes in the repertoire of HA+ B-cells in
      longitudinal samples from large cohorts of vaccinees and infected subjects with
      the ultimate goal of understanding the in vivo B-cell dynamics driving the
      evolution of broadly cross-protective antibody responses.

PMID- 23976948
TI  - Fast docking on graphics processing units via Ray-Casting.
AB  - Docking Approach using Ray Casting (DARC) is structure-based computational method
      for carrying out virtual screening by docking small-molecules into protein
      surface pockets. In a complementary study we find that DARC can be used to
      identify known inhibitors from large sets of decoy compounds, and can identify
      new compounds that are active in biochemical assays. Here, we describe our
      adaptation of DARC for use on Graphics Processing Units (GPUs), leading to a
      speedup of approximately 27-fold in typical-use cases over the corresponding
      calculations carried out using a CPU alone. This dramatic speedup of DARC will
      enable screening larger compound libraries, screening with more conformations of
      each compound, and including multiple receptor conformations when screening. We
      anticipate that all three of these enhanced approaches, which now become
      tractable, will lead to improved screening results. 

PMID- 23976949
TI  - Metabolic engineering of the phenylpropanoid pathway enhances the antioxidant
      capacity of Saussurea involucrata.
AB  - The rare wild species of snow lotus Saussurea involucrata is a commonly used
      medicinal herb with great pharmacological value for human health, resulting from
      its uniquely high level of phenylpropanoid compound production. To gain
      information on the phenylpropanid biosynthetic pathway genes in this critically
      important medicinal plant, global transcriptome sequencing was performed. It
      revealed that the phenylpropanoid pathway genes were well represented in S.
      involucrata. In addition, we introduced two key phenylpropanoid pathway inducing
      transcription factors (PAP1 and Lc) into this medicinal plant. Transgenic S.
      involucrata co-expressing PAP1 and Lc exhibited purple pigments due to a massive
      accumulation of anthocyanins. The over-expression of PAP1 and Lc largely
      activated most of the phenylpropanoid pathway genes, and increased accumulation
      of several phenylpropanoid compounds significantly, including chlorogenic acid,
      syringin, cyanrine and rutin. Both ABTS (2,2'-azinobis-3-ethylbenzotiazo-line-6
      sulfonic acid) and FRAP (ferric reducing anti-oxidant power) assays revealed that
      the antioxidant capacity of transgenic S. involucrata lines was greatly enhanced
      over controls. In addition to providing a deeper understanding of the molecular
      basis of phenylpropanoid metabolism, our results potentially enable an
      alternation of bioactive compound production in S. involucrata through metabolic
      engineering. 

PMID- 23976950
TI  - Noise exposure and hearing impairment among Chinese restaurant workers and
      entertainment employees in Hong Kong.
AB  - BACKGROUND: Noise-induced hearing loss (NIHL) is a major concern in the non
      manufacturing industries. This study aimed to investigate the occupational noise
      exposure and the NIHL among Chinese restaurant workers and entertainment
      employees working in the service industry in Hong Kong. METHODS: This cross
      sectional survey involved a total of 1,670 participants. Among them, 937 were
      randomly selected from the workers of Chinese restaurants and 733 were selected
      from workers in three entertainment sectors: radio and television stations;
      cultural performance halls or auditoria of the Leisure and Cultural Services
      Department (LCSD); and karaoke bars. Noise exposure levels were measured in the
      sampled restaurants and entertainment sectors. Each participant received an
      audiometric screening test. Those who were found to have abnormalities were
      required to take another diagnostic test in the health center. The "Klockhoff
      digit" method was used to classify NIHL in the present study. RESULTS: The main
      source of noise inside restaurants was the stoves. The mean hearing thresholds
      showed a typical dip at 3 to 6 KHz and a substantial proportion (23.7%) of the
      workers fulfilled the criteria for presumptive NIHL. For entertainment sectors,
      employees in radio and television stations generally had higher exposure levels
      than those in the halls or auditoria of the LCSD and karaoke bars. The mean
      hearing thresholds showed a typical dip at 6 KHz and a substantial proportion of
      the employees fulfilled the criteria for presumptive NIHL (38.6%, 95%CI: 35.1
      42.1%). Being male, older, and having longer service and daily alcohol
      consumption were associated with noise-induced hearing impairment both in
      restaurant workers and entertainment employees. CONCLUSION: Excessive noise
      exposure is common in the Chinese restaurant and entertainment industries and a
      substantial proportion of restaurant workers and entertainment employees suffer
      from NIHL. Comprehensive hearing conservation programs should be introduced to
      the service industry in Hong Kong.

PMID- 23976951
TI  - Loss of the nuclear receptor corepressor SLIRP compromises male fertility.
AB  - Nuclear receptors (NRs) and their coregulators play fundamental roles in
      initiating and directing gene expression influencing mammalian reproduction,
      development and metabolism. SRA stem Loop Interacting RNA-binding Protein (SLIRP)
      is a Steroid receptor RNA Activator (SRA) RNA-binding protein that is a potent
      repressor of NR activity. SLIRP is present in complexes associated with NR target
      genes in the nucleus; however, it is also abundant in mitochondria where it
      affects mitochondrial mRNA transcription and energy turnover. In further
      characterisation studies, we observed SLIRP protein in the testis where its
      localization pattern changes from mitochondrial in diploid cells to peri
      acrosomal and the tail in mature sperm. To investigate the in vivo effects of
      SLIRP, we generated a SLIRP knockout (KO) mouse. This animal is viable, but sub
      fertile. Specifically, when homozygous KO males are crossed with wild type (WT)
      females the resultant average litter size is reduced by approximately one third
      compared with those produced by WT males and females. Further, SLIRP KO mice
      produced significantly fewer progressively motile sperm than WT animals. Electron
      microscopy identified disruption of the mid-piece/annulus junction in homozygous
      KO sperm and altered mitochondrial morphology. In sum, our data implicates SLIRP
      in regulating male fertility, wherein its loss results in asthenozoospermia
      associated with compromised sperm structure and mitochondrial morphology. 

PMID- 23976953
TI  - Thioredoxin-interacting protein regulates glucose metabolism and affects
      cytoplasmic streaming in mouse oocytes.
AB  - Thioredoxin-interacting protein (Txnip) regulates intracellular redox state and
      prompts oxidative stress by binding to and inhibiting Thioredoxin (Trx). In
      addition, via a Trx-independent mechanism, Txnip regulates glucose metabolism and
      thus maintains intracellular glucose levels. Previously, we found Txnip mRNA
      highly expressed in immature germinal vesicle (GV) oocytes, but currently there
      is no report describing the role of Txnip in oocytes. Therefore, we conducted the
      present study to determine the function of Txnip in mouse oocytes' maturation and
      meiosis by using RNA interference (RNAi) method. Upon specific depletion of
      Txnip, 79.5% of oocytes were arrested at metaphase I (MI) stage. Time-lapse video
      microscopy analysis revealed that the formation of granules in the oocyte
      cytoplasm increased concurrent with retarded cytoplasmic streaming after Txnip
      RNAi treatment. Txnip RNAi-treated oocytes had upregulated glucose uptake and
      lactate production. To confirm the supposition that mechanism responsible for
      these observed phenomena involves increased lactate in oocytes, we cultured
      oocytes in high lactate medium and observed the same increased granule formation
      and retarded cytoplasmic streaming as found by Txnip RNAi. The MI-arrested
      oocytes exhibited scattered microtubules and aggregated chromosomes indicating
      that actin networking was disturbed by Txnip RNAi. Therefore, we conclude that
      Txnip is a critical regulator of glucose metabolism in oocytes and is involved in
      maintaining cytoplasmic streaming in mouse oocytes. 

PMID- 23976952
TI  - Selective kappa opioid antagonists nor-BNI, GNTI and JDTic have low affinities
      for non-opioid receptors and transporters.
AB  - BACKGROUND: Nor-BNI, GNTI and JDTic induce selective kappa opioid antagonism that
      is delayed and extremely prolonged, but some other effects are of rapid onset and
      brief duration. The transient effects of these compounds differ, suggesting that
      some of them may be mediated by other targets. RESULTS: In binding assays, the
      three antagonists showed no detectable affinity (K(i)>=10 uM) for most non-opioid
      receptors and transporters (26 of 43 tested). There was no non-opioid target for
      which all three compounds shared detectable affinity, or for which any two shared
      sub-micromolar affinity. All three compounds showed low nanomolar affinity for
      kappa opioid receptors, with moderate selectivity over MU and delta (3 to 44
      fold). Nor-BNI bound weakly to the alpha(2C)-adrenoceptor (K(i) = 630 nM). GNTI
      enhanced calcium mobilization by noradrenaline at the alpha(1A)-adrenoceptor
      (EC50 = 41 nM), but did not activate the receptor, displace radioligands, or
      enhance PI hydrolysis. This suggests that it is a functionally-selective
      allosteric enhancer. GNTI was also a weak M1 receptor antagonist (K(B) = 3.7 uM).
      JDTic bound to the noradrenaline transporter (K(i) = 54 nM), but only weakly
      inhibited transport (IC50 = 1.1 uM). JDTic also bound to the opioid-like receptor
      NOP (K(i) = 12 nM), but gave little antagonism even at 30 uM. All three compounds
      exhibited rapid permeation and active efflux across Caco-2 cell monolayers.
      CONCLUSIONS: Across 43 non-opioid CNS targets, only GNTI exhibited a potent
      functional effect (allosteric enhancement of alpha(1A)-adrenoceptors). This may
      contribute to GNTI's severe transient effects. Plasma concentrations of nor-BNI
      and GNTI may be high enough to affect some peripheral non-opioid targets.
      Nonetheless, kappa opioid antagonism persists for weeks or months after these
      transient effects dissipate. With an adequate pre-administration interval, our
      results therefore strengthen the evidence that nor-BNI, GNTI and JDTic are highly
      selective kappa opioid antagonists.

PMID- 23976954
TI  - Nimotuzumab enhances the radiosensitivity of cancer cells in vitro by inhibiting
      radiation-induced DNA damage repair.
AB  - BACKGROUND: Nimotuzumab is a humanized IgG1 monoclonal antibody specifically
      targeting EGFR. In this study, we aimed to investigate the molecular mechanisms
      of nimotuzumab in its effects of enhancing cancer cell radiosensitivity.
      PRINCIPAL FINDING: Lung cancer A549 cells and breast cancer MCF-7 cells were
      pretreated with or without nimotuzumab for 24 h before radiation to perform the
      clonogenic survival assay and to analyze the cell apoptosis by flow ctyometry.
      gamma-H2AX foci were detected by confocal microscopy to assess the effect of
      nimotuzumab on radiation induced DNA repair. EGFR activation was examined and the
      levels of DNA damage repair related proteins in A549 cells at different time
      point and at varying doses exposure after nimotuzumab and radiation treatment
      were examined by Western blot. Pretreatment with nimotuzumab reduced clonogenic
      survival after radiation, inhibited radiation-induced EGFR activation and
      increased the radiation-induced apoptosis in both A549 cells and MCF-7 cells. The
      foci of gamma-H2AX 24 h after radiation significantly increased in nimotuzumab
      pretreated cells with different doses. The phosphorylation of AKT and DNA-PKcs
      were remarkably inhibited in the combination group at each dose point as well as
      time point. CONCLUSIONS: Our results revealed that the possible mechanism of
      nimotuzumab enhancing the cancer radiosensitivity is that nimotuzumab inhibited
      the radiation-induced activation of DNA-PKcs through blocking the PI3K/AKT
      pathway, which ultimately affected the DNA DSBs repair.

PMID- 23976955
TI  - An NO donor approach to neuroprotective and procognitive estrogen therapy
      overcomes loss of NO synthase function and potentially thrombotic risk.
AB  - Selective estrogen receptor modulators (SERMs) are effective therapeutics that
      preserve favorable actions of estrogens on bone and act as antiestrogens in
      breast tissue, decreasing the risk of vertebral fractures and breast cancer, but
      their potential in neuroprotective and procognitive therapy is limited by: 1) an
      increased lifetime risk of thrombotic events; and 2) an attenuated response to
      estrogens with age, sometimes linked to endothelial nitric oxide synthase (eNOS)
      dysfunction. Herein, three 3(rd) generation SERMs with similar high affinity for
      estrogen receptors (ERalpha, ERbeta) were studied: desmethylarzoxifene (DMA),
      FDMA, and a novel NO-donating SERM (NO-DMA). Neuroprotection was studied in
      primary rat neurons exposed to oxygen glucose deprivation; reversal of
      cholinergic cognitive deficit was studied in mice in a behavioral model of
      memory; long term potentiation (LTP), underlying cognition, was measured in
      hippocampal slices from older 3*Tg Alzheimer's transgenic mice; vasodilation was
      measured in rat aortic strips; and anticoagulant activity was compared.
      Pharmacologic blockade of GPR30 and NOS; denudation of endothelium; measurement
      of NO; and genetic knockout of eNOS were used to probe mechanism. Comparison of
      the three chemical probes indicates key roles for GPR30 and eNOS in mediating
      therapeutic activity. Procognitive, vasodilator and anticoagulant activities of
      DMA were found to be eNOS dependent, while neuroprotection and restoration of LTP
      were both shown to be dependent upon GPR30, a G-protein coupled receptor
      mediating estrogenic function. Finally, the observation that an NO-SERM shows
      enhanced vasodilation and anticoagulant activity, while retaining the positive
      attributes of SERMs even in the presence of NOS dysfunction, indicates a
      potential therapeutic approach without the increased risk of thrombotic events.

PMID- 23976956
TI  - Ca2+/calmodulin-dependent protein kinase II contributes to hypoxic ischemic cell
      death in neonatal hippocampal slice cultures.
AB  - We have recently shown that p38MAP kinase (p38MAPK) stimulates ROS generation via
      the activation of NADPH oxidase during neonatal hypoxia-ischemia (HI) brain
      injury. However, how p38MAPK is activated during HI remains unresolved and was
      the focus of this study. Ca2+/calmodulin-dependent protein kinase II (CaMKII)
      plays a key role in brain synapse development, neural transduction and synaptic
      plasticity. Here we show that CaMKII activity is stimulated in rat hippocampal
      slice culture exposed to oxygen glucose deprivation (OGD) to mimic the condition
      of HI. Further, the elevation of CaMKII activity, correlated with enhanced
      p38MAPK activity, increased superoxide generation from NADPH oxidase as well as
      necrotic and apoptotic cell death. All of these events were prevented when CaMKII
      activity was inhibited with KN93. In a neonatal rat model of HI, KN93 also
      reduced brain injury. Our results suggest that CaMKII activation contributes to
      the oxidative stress associated with neural cell death after HI.

PMID- 23976957
TI  - Phenyl 1,2,3-triazole-thymidine ligands stabilize G-quadruplex DNA, inhibit DNA
      synthesis and potentially reduce tumor cell proliferation over 3'-azido
      deoxythymidine.
AB  - Triazoles are known for their non-toxicity, higher stability and therapeutic
      activity. Few nucleoside (L1, L2 and L3) and non-nucleoside 1,2,3-triazoles (L4
      L14) were synthesised using click chemistry and they were screened for tumor cell
      cytotoxicity and proliferation. Among these triazole ligands studied, nucleoside
      ligands exhibited higher potential than non-nucleoside ligands. The nucleoside
      triazole analogues, 3'-Phenyl-1,2,3- triazole-thymidine (L2) and 3'-4
      Chlorophenyl-1,2,3-triazole-thymidine (L3), demonstrated higher cytotoxicity in
      tumor cells than in normal cells. The IC50 value for L3 was lowest (50 uM) among
      the ligands studied. L3 terminated cell cycle at S, G2/M phases and enhanced sub
      G1 populations, manifesting induction of apoptosis in tumor cells. Confocal
      studies indicated that nucleoside triazole ligands (L2/L3) cause higher DNA
      fragmentation than other ligands. Preclinical experiments with tumor-induced mice
      showed greater reduction in tumor size with L3. In vitro DNA synthesis reaction
      with L3 exhibited higher DNA synthesis inhibition with quadruplex forming DNA (QF
      DNA) than non quadruplex forming DNA (NQF DNA). T(m) of quadruplex DNA increased
      in the presence of L3, indicating its ability to enhance stability of quadruplex
      DNA at elevated temperature and the results indicate that it had higher affinity
      towards quadruplex DNA than the other forms of DNA (like dsDNA and ssDNA). From
      western blot experiment, it was noticed that telomerase expression levels in the
      tissues of tumor-induced mice were found to be reduced on L3 treatment.
      Microcalorimetry results emphasise that two nucleoside triazole ligands (L2/L3)
      interact with quadruplex DNA with significantly higher affinity (K(d)~10-7 M).
      Interestingly the addition of an electronegative moiety to the phenyl group of L2
      enhanced its anti-proliferative activity. Though IC50 values are not
      significantly low with L3, the studies on series of synthetic 1,2,3-triazole
      ligands are useful for improving and building potential pro-apoptotic ligands.

PMID- 23976958
TI  - Dopamine D1 receptor gene variation modulates opioid dependence risk by affecting
      transition to addiction.
AB  - Dopamine D1 receptor (DRD1) modulates opioid reinforcement, reward, and opioid
      induced neuroadaptation. We propose that DRD1 polymorphism affects susceptibility
      to opioid dependence (OD), the efficiency of transition to OD, and opioid-induced
      pleasure response. We analyzed potential association between seven DRD1
      polymorphisms with the following traits: duration of transition from the first
      use to dependence (DTFUD), subjective pleasure responses to opioid on first use
      and post-dependence use, and OD risk in 425 Chinese with OD and 514 healthy
      controls. DTFUD and level of pleasure responses were examined using a semi
      structured interview. The DTFUD of opioid addicts ranged from 5 days to 11 years.
      Most addicts (64.0%) reported non-comfortable response upon first opioid use,
      while after dependence, most addicts (53.0%) felt strong opioid-induced pleasure.
      Survival analysis revealed a correlation of prolonged DTFUD with the minor allele
      carrying genotypes of DRD1 rs4532 (hazard ratios (HR) = 0.694; p = 0.001) and
      rs686 (HR = 0.681, p = 0.0003). Binary logistic regression indicated that
      rs10063995 GT genotype (vs. GG+TT, OR = 0.261) could predict decreased pleasure
      response to first-time use and the minor alleles of rs686 (OR = 0.535) and rs4532
      (OR = 0.537) could predict decreased post-dependence pleasure. Moreover, rs686
      minor allele was associated with a decreased risk for rapid transition from
      initial use to dependence (DTFUD<=30 days; OR = 0.603) or post-dependence
      euphoria (OR = 0.603) relative to major allele. In conclusion, DRD1 rs686 minor
      allele decreases the OD risk by prolonging the transition to dependence and
      attenuating opioid-induced pleasure in Chinese. 

PMID- 23976959
TI  - Tumor homogeneity between primary and metastatic sites for BRAF status in
      metastatic melanoma determined by immunohistochemical and molecular testing.
AB  - BRAF inhibitors have demonstrated improvement of overall survival in patients
      with metastatic melanoma and BRAF(V600) mutations. In order to evaluate BRAF
      tumor heterogeneity between primary and metastatic site, we have evaluated the
      performance of immunohistochemistry (IHC) with an anti-BRAF(V600E) antibody in
      both localization by comparison with high resolution melting analysis followed by
      Sanger sequencing in a parallel blinded study. A total of 230 samples distributed
      as primary melanoma (n = 88) and different types of metastatic samples (n = 142)
      were studied in 99 patients with advanced or metastatic melanoma (stage III or
      IV). The prevalence of each BRAF mutation was c.1799T>A, BRAF(V600E) (45.2%),
      c.1799_1800TG>AA, BRAF(V600E2) (3.0%), c.1798_1799GT>AA, BRAF(V600K) (3.0%),
      c.1801 A>G, BRAF(K601E) (1.3%), c.1789_1790CT>TC, BRAF(L597S) (0.4%), c.1780G>A,
      BRAF(D594N) (0.9%) respectively. IHC was positive in 109/112 samples harboring
      BRAF(V600E/E2) mutations and negative in other cases. The cytoplasmic staining
      was either strongly positive in tumor cells of BRAF(V600E) mutated cases. It
      appeared strong brown, different from the vesicular grey cytoplasmic pigmentation
      of melanophages. Concordance between the two techniques was 96.4%. Sensitivity of
      IHC for detecting the BRAF(V600E/E2) mutations was 97.3%, while specificity was
      100%. Both our IHC and molecular study demonstrated homogeneity between primary
      and metastatic sites for BRAF status in melanoma. This study also provides
      evidence that IHC may be a cost-effective first-line method for BRAF(V600E)
      detection. Thereafter, molecular techniques should be used in negative, ambiguous
      or non-contributive cases. 

PMID- 23976960
TI  - Clinical trial to evaluate the safety and immunogenicity of a trivalent surface
      antigen seasonal influenza vaccine produced in mammalian cell culture and
      administered to young and elderly adults with and without A(H1N1) pre
      vaccination.
AB  - Vaccination against influenza is an important means of reducing morbidity and
      mortality in subjects at risk. The prevalent viral strains responsible for
      seasonal epidemics usually change annually, but the WHO recommendations for the
      2011/2012-season in the Northern hemisphere included the same antigens as for the
      previous season. We conducted a single-center, single-arm study involving 62
      younger (18-60 years) and 64 older (>60 years) adults to test the immunogenicity,
      safety and tolerability of a trivalent surface antigen, inactivated influenza
      vaccine produced in mammalian cell-culture. The vaccine contained 15 ug
      hemagglutinin of each of the virus strains recommended for the 2011-2012 Northern
      hemisphere winter season (A/California/7/09 (H1N1)-; A/Perth/16/09 (H3N2)-;
      B/Brisbane/60/08-like strain) in a non-adjuvanted preservative-free formulation.
      Antibody response was measured by hemagglutination inhibition 21 days after
      immunization. Adverse events and safety were assessed using subject diary cards
      and telephone interviews. Seroconversion or a 4-fold antibody increase in
      antibody titers was detectable against A(H1N1) in 68% of both younger and older
      adults, against A(H3N2) in 53% and 27%, and against the B influenza strain in 35%
      and 17%. Antibody titers of 40 or more were observed against A(H1N1) in 87% and
      90% of younger and older adults, against A(H3N2) in 98% and 98%, and against the
      B influenza strain in 93% and 90%. Pre-vaccination antibody titers were
      protective against A(H1N1), A(H3N2) and B in 38%, 58% and 58%, respectively, of
      younger and in 43%, 88% and 70% of older adults. Among subjects with previous
      A(H1N1) vaccination only 48% of younger and 47% of older adults had protective
      A(H1N1) antibodies at inclusion. Adverse reactions were generally mild. The most
      frequently reported reactions were pain at the injection site, myalgia and
      fatigue. The vaccine generated protective antibodies against all three viral
      strains and had an acceptable safety profile in both younger and older adults.
      TRIAL REGISTRATION: ClinicalTrials.govNCT01422512.

PMID- 23976961
TI  - Synchronization, slippage, and unbundling of driven helical flagella.
AB  - Peritrichous bacteria exploit bundles of helical flagella for propulsion and
      chemotaxis. Here, changes in the swimming direction (tumbling) are induced by a
      change of the rotational frequency of some flagella. Employing coarse-grained
      modeling and simulations, we investigate the dynamical properties of helical
      flagella bundles driven by mismatched motor torques. Over a broad range of
      distances between the flagella anchors and applied torque differences, we find a
      stable bundled state, which is important for a robust directional motion of a
      bacterium. With increasing torque difference, a phase lag in the flagellar
      rotations develops, followed by slippage and ultimately unbundling, which
      sensitively depends on the anchoring distance of neighboring flagella. In the
      slippage and drift states, the different rotation frequencies of the flagella
      generate a tilting torque on the bacterial body, which implies a change of the
      swimming direction as observed experimentally. 

PMID- 23976962
TI  - Are Namibian "fairy circles" the consequence of self-organizing spatial
      vegetation patterning?
AB  - Causes of over-dispersed barren "fairy circles" that are often surrounded by ca.
      0.5 m tall peripheral grasses in a matrix of shorter (ca. 0.2 m tall) grasses in
      Namibian grasslands remain mysterious. It was hypothesized that the fairy circles
      are the consequence of self-organizing spatial vegetation patterning arising from
      resource competition and facilitation. We examined the edaphic properties of
      fairy circles and variation in fairy circle size, density and landscape occupancy
      (% land surface) with edaphic properties and water availability at a local scale
      (<50 km) and with climate and vegetation characteristics at a regional scale.
      Soil moisture in the barren fairy circles declines from the center towards the
      periphery and is inversely correlated with soil organic carbon, possibly
      indicating that the peripheral grass roots access soil moisture that persists
      into the dry season within fairy circles. Fairy circle landscape occupancy is
      negatively correlated with precipitation and soil [N], consistent with fairy
      circles being the product of resource-competition. Regional fairy circle
      presence/absence is highly predictable using an empirical model that includes
      narrow ranges of vegetation biomass, precipitation and temperature seasonality as
      predictor variables, indicating that fairy circles are likely a climate-dependent
      emergent phenomenon. This dependence of fairy circle occurrence on climate
      explains why fairy circles in some locations may appear and disappear over time.
      Fairy circles are only over-dispersed at high landscape occupancies, indicating
      that inter-circle competition may determine their spacing. We conclude that fairy
      circles are likely to be an emergent arid-grassland phenomenon that forms as a
      consequence of peripheral grass resource-competition and that the consequent
      barren circle may provide a resource-reservoir essential for the survival of the
      larger peripheral grasses and provides a habitat for fossicking fauna. 

PMID- 23976963
TI  - Development and characterization of a Psathyrostachys huashanica Keng 7Ns
      chromosome addition line with leaf rust resistance.
AB  - The aim of this study was to characterize a Triticum aestivum-Psathyrostachys
      huashanica Keng (2n = 2x = 14, NsNs) disomic addition line 2-1-6-3. Individual
      line 2-1-6-3 plants were analyzed using cytological, genomic in situ
      hybridization (GISH), EST-SSR, and EST-STS techniques. The alien addition line 2
      1-6-3 was shown to have two P. huashanica chromosomes, with a meiotic
      configuration of 2n = 44 = 22 II. We tested 55 EST-SSR and 336 EST-STS primer
      pairs that mapped onto seven different wheat chromosomes using DNA from parents
      and the P. huashanica addition line. One EST-SSR and nine EST-STS primer pairs
      indicated that the additional chromosome of P. huashanica belonged to
      homoeologous group 7, the diagnostic fragments of five EST-STS markers (BE404955,
      BE591127, BE637663, BF482781 and CD452422) were cloned, sequenced and compared.
      The results showed that the amplified polymorphic bands of P. huashanica and
      disomic addition line 2-1-6-3 shared 100% sequence identity, which was designated
      as the 7Ns disomic addition line. Disomic addition line 2-1-6-3 was evaluated to
      test the leaf rust resistance of adult stages in the field. We found that one
      pair of the 7Ns genome chromosomes carried new leaf rust resistance gene(s).
      Moreover, wheat line 2-1-6-3 had a superior numbers of florets and grains per
      spike, which were associated with the introgression of the paired P. huashanica
      chromosomes. These high levels of disease resistance and stable, excellent
      agronomic traits suggest that this line could be utilized as a novel donor in
      wheat breeding programs. 

PMID- 23976964
TI  - Insomnia, excessive sleepiness, excessive fatigue, anxiety, depression and shift
      work disorder in nurses having less than 11 hours in-between shifts.
AB  - STUDY OBJECTIVE: To assess if less than 11 hours off work between work shifts
      (quick returns) was related to insomnia, sleepiness, fatigue, anxiety, depression
      and shift work disorder among nurses. METHODS: A questionnaire including
      established instruments measuring insomnia (Bergen Insomnia Scale), sleepiness
      (Epworth Sleepiness Scale), fatigue (Fatigue Questionnaire), anxiety/depression
      (Hospital Anxiety and Depression Scale) and shift work disorder was administered.
      Among the 1990 Norwegian nurses who participated in the study; 264 nurses had no
      quick returns, 724 had 1-30 quick returns and 892 had more than 30 quick returns
      during the past year. 110 nurses did not report the number of quick returns
      during the past year. The prevalence of insomnia, excessive sleepiness, excessive
      fatigue, anxiety, depression and shift work disorder was calculated within the
      three groups of nurses. Crude and adjusted logistic regression analyses were
      performed to assess the relation between quick returns and such complaints.
      RESULTS: We found a significant positive association between quick returns and
      insomnia, excessive sleepiness, excessive fatigue and shift work disorder.
      Anxiety and depression were not related to working quick returns. CONCLUSIONS:
      There is a health hazard associated with quick returns. Further research should
      aim to investigate if workplace strategies aimed at reducing the number of quick
      returns may reduce complaints among workers.

PMID- 23976965
TI  - Collagen peptides in urine: a new promising biomarker for the detection of
      colorectal liver metastases.
AB  - INTRODUCTION: For both patients and the outpatient clinic the frequent follow-up
      visits after a resection of colorectal cancer (CRC) are time consuming and due to
      large patient numbers expensive. Therefore it is important to develop an
      effective non-invasive test for the detection of colorectal liver metastasis
      (CRLM) which could be used outside the hospital. The urine proteome is known to
      provide detailed information for monitoring changes in the physiology of humans.
      Urine collection is non-invasive and urine naturally occurring peptides (NOPs)
      have the advantage of being easily accessible without labour-intensive sample
      preparation. These advantages make it potentially useful for a quick and reliable
      application in clinical settings. In this study, we will focus on the
      identification and validation of urine NOPs to discriminate patients with CRLM
      from healthy controls. MATERIALS AND METHODS: Urine samples were collected from
      24 patients with CRLM and 25 healthy controls. In the first part of the study,
      samples were measured with a nano liquid chromatography (LC) system (Thermo
      Fisher Scientific, Germaring, Germany) coupled on-line to a hybrid linear ion
      trap/Orbitrap mass spectrometer (LTQ-Orbitrap-XL, Thermo Fisher Scientific,
      Bremen, Germany). A discovery set was used to construct the model and
      consecutively the validation set, being independent from the discovery set, to
      check the acquired model. From the peptides which were selected, multiple
      reaction monitoring (MRM's) were developed on a UPLC-MS/MS system. RESULTS: Seven
      peptides were selected and applied in a discriminant analysis a sensitivity of
      84.6% and a specificity of 92.3% were established (Canonical correlation:0.797,
      Eigenvalue:1.744, F:4.49, p:0.005). The peptides AGPP(-OH)GEAGKP(-OH)GEQGVP(
      OH)GDLGA P(-OH)GP and KGNSGEP(-OH)GAPGSKGDTGAKGEP(-OH)GPVG were selected for
      further quantitative analysis which showed a sensitivity of 88% and a specificity
      of 88%. CONCLUSION: Urine proteomic analysis revealed two very promising
      peptides, both part from collagen type 1, AGPP(-OH)GEAGKP(-OH)GEQGVP(-OH)GDLGAP(
      OH)GP and KGNSGEP(-OH)GAPGSKGDTGAKGEP(-OH)GPVG which could detect CRLM in a non
      invasive manner.

PMID- 23976966
TI  - Temporal dynamics of visual attention measured with event-related potentials.
AB  - How attentional modulation on brain activities determines behavioral performance
      has been one of the most important issues in cognitive neuroscience. This issue
      has been addressed by comparing the temporal relationship between attentional
      modulations on neural activities and behavior. Our previous study measured the
      time course of attention with amplitude and phase coherence of steady-state
      visual evoked potential (SSVEP) and found that the modulation latency of phase
      coherence rather than that of amplitude was consistent with the latency of
      behavioral performance. In this study, as a complementary report, we compared the
      time course of visual attention shift measured by event-related potentials (ERPs)
      with that by target detection task. We developed a novel technique to compare
      ERPs with behavioral results and analyzed the EEG data in our previous study. Two
      sets of flickering stimulus at different frequencies were presented in the left
      and right visual hemifields, and a target or distracter pattern was presented
      randomly at various moments after an attention-cue presentation. The observers
      were asked to detect targets on the attended stimulus after the cue. We found
      that two ERP components, P300 and N2pc, were elicited by the target presented at
      the attended location. Time-course analyses revealed that attentional modulation
      of the P300 and N2pc amplitudes increased gradually until reaching a maximum and
      lasted at least 1.5 s after the cue onset, which is similar to the temporal
      dynamics of behavioral performance. However, attentional modulation of these ERP
      components started later than that of behavioral performance. Rather, the time
      course of attentional modulation of behavioral performance was more closely
      associated with that of the concurrently recorded SSVEPs analyzed. These results
      suggest that neural activities reflected not by either the P300 or N2pc, but by
      the SSVEPs, are the source of attentional modulation of behavioral performance. 

PMID- 23976967
TI  - Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma
      (MPM).
AB  - Malignant Pleural Mesothelioma (MPM) is an aggressive cancer that is often
      diagnosed at an advanced stage and is characterized by a long latency period (20
      40 years between initial exposure and diagnosis) and prior exposure to asbestos.
      Currently accurate diagnosis of MPM is difficult due to the lack of sensitive
      biomarkers and despite minor improvements in treatment, median survival rates do
      not exceed 12 months. Accumulating evidence suggests that aberrant expression of
      long non-coding RNAs (lncRNAs) play an important functional role in cancer
      biology. LncRNAs are a class of recently discovered non-protein coding RNAs >200
      nucleotides in length with a role in regulating transcription. Here we used NCode
      long noncoding microarrays to identify differentially expressed lncRNAs
      potentially involved in MPM pathogenesis. High priority candidate lncRNAs were
      selected on the basis of statistical (P<0.05) and biological significance (>3
      fold difference). Expression levels of 9 candidate lncRNAs were technically
      validated using RT-qPCR, and biologically validated in three independent test
      sets: (1) 57 archived MPM tissues obtained from extrapleural pneumonectomy
      patients, (2) 15 cryopreserved MPM and 3 benign pleura, and (3) an extended panel
      of 10 MPM cell lines. RT-qPCR analysis demonstrated consistent up-regulation of
      these lncRNAs in independent datasets. ROC curve analysis showed that two
      candidates were able to separate benign pleura and MPM with high sensitivity and
      specificity, and were associated with nodal metastases and survival following
      induction chemotherapy. These results suggest that lncRNAs have potential to
      serve as biomarkers in MPM. 

PMID- 23976968
TI  - Ginsenoside Rd attenuates myocardial ischemia/reperfusion injury via Akt/GSK
      3beta signaling and inhibition of the mitochondria-dependent apoptotic pathway.
AB  - Evidence suggests Ginsenoside Rd (GSRd), a biologically active extract from the
      medical plant Panax Ginseng, exerts antioxidant effect, decreasing reactive
      oxygen species (ROS) formation. Current study determined the effect of GSRd on
      myocardial ischemia/reperfusion (MI/R) injury (a pathological condition where ROS
      production is significantly increased) and investigated the underlying
      mechanisms. The current study utilized an in vivo rat model of MI/R injury and an
      in vitro neonatal rat cardiomyocyte (NRC) model of simulated ischemia/reperfusion
      (SI/R) injury. Infarct size was measured by Evans blue/TTC double staining. NRC
      injury was determined by MTT and lactate dehydrogenase (LDH) leakage assay. ROS
      accumulation and apoptosis were assessed by flow cytometry. Mitochondrial
      membrane potential (MMP) was determined by 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'
      tetrathylbenzimidazol carbocyanine iodide (JC-1). Cytosolic translocation of
      mitochondrial cytochrome c and expression of caspase-9, caspase-3, Bcl-2 family
      proteins, and phosphorylated Akt and GSK-3beta were determined by western blot.
      Pretreatment with GSRd (50 mg/kg) significantly augmented rat cardiac function,
      as evidenced by increased left ventricular ejection fraction (LVEF) and +/-dP/dt.
      GSRd reduced myocardial infarct size, apoptotic cell death, and blood creatine
      kinase/lactate dehydrogenase levels after MI/R. In NRCs, GSRd (10 uM) inhibited
      SI/R-induced ROS generation (P<0.01), decreased cellular apoptosis, stabilized
      the mitochondrial membrane potential (MMP), and attenuated cytosolic
      translocation of mitochondrial cytochrome c. GSRd inhibited activation of caspase
      9 and caspase-3, increased the phosphorylated Akt and GSK-3beta, and increased
      the Bcl-2/Bax ratio. Together, these data demonstrate GSRd mediated
      cardioprotective effect against MI/R-induced apoptosis via a mitochondrial
      dependent apoptotic pathway. 

PMID- 23976969
TI  - Problems in cross-cultural use of the hospital anxiety and depression scale: "no
      butterflies in the desert".
AB  - OBJECTIVE: The Hospital Anxiety and Depression Scale (HADS) is widely used to
      screen for anxiety and depression. A large literature is citable in support of
      its validity, but difficulties are increasingly being identified, such as
      inexplicably discrepant optimal cutpoints and inconsistent factor-structures.
      This article examines whether these problems could be due to the construction of
      the HADS that poses difficulties for translation and cross-cultural use. METHODS:
      Authors' awareness of difficulties translating the HADS were identified by
      examining 20% of studies using the HADS, obtained by a systematic literature
      search in Pubmed and PsycINFO in May 2012. Reports of use of translations and
      validation studies were recorded for papers from non-English speaking countries.
      Narrative and systematic reviews were examined for how authors dealt with
      different translations. RESULTS: Of 417 papers from non-English speaking
      countries, only 45% indicated whether a translation was used. Studies validating
      translations were cited in 54%. Seventeen reviews, incorporating data from
      diverse translated versions, were examined. Only seven mentioned issues of
      language and culture, and none indicated insurmountable problems in integrating
      results from different translations. CONCLUSION: Initial decisions concerning
      item content and response options likely leave the HADS difficult to translate,
      but we failed to find an acknowledgment of problems in articles involving its
      translation and cross-cultural use. Investigators' lack of awareness of these
      issues can lead to anomalous results and difficulties in interpretation and
      integration of these results. Reviews tend to overlook these issues and most
      reviews indiscriminately integrate results from studies performed in different
      countries. Cross-culturally valid, but literally translated versions of the HADS
      may not be attainable, and specific cutpoints may not be valid across cultures
      and language. Claims about rates of anxiety and depression based on integrating
      cross-cultural data or using the same cutpoint across languages and culture
      should be subject to critical scrutiny.

PMID- 23976970
TI  - Single nucleotide polymorphisms of PIN1 promoter region and cancer risk: evidence
      from a meta-analysis.
AB  - BACKGROUND: Peptidylprolyl cis/trans isomerase NIMA-interacting 1 (PIN1) is
      involved in the process of tumorigenesis. The two single nucleotide polymorphisms
      (-677T>C, -842G>C) in the PIN1 promoter region have been suspected of being
      associated with cancer risk for years, but the conclusion is still inconclusive.
      METHODS: Eligible case-control studies were retrieved by searching databases and
      references of related reviews and studies. Genotype distribution data, adjusted
      odds ratios (ORs) and 95% confidence (CIs) intervals were extracted to calculate
      pooled ORs. RESULTS: A total of 4619 cancer cases and 4661 controls were included
      in this meta-analysis. Overall, the PIN1 -667T>C polymorphism was not associated
      with cancer risk, while the -842C allele was significantly associated with
      reduced cancer risk (CC+GC vs. GG, OR = 0.725, 95% CI: 0.607-0.865;
      P(heterogeneity) = 0.012 and GC vs. GG: OR = 0.721, 95% CI: 0.591-0.880;
      P(heterogeneity) = 0.003). Results from genotype distribution data were in
      agreement with those calculated with adjusted ORs and 95% CIs. No publication
      bias was detected. CONCLUSIONS: Results of this meta-analysis suggest that the
      PIN1 -842G>C polymorphism is associated with decreased cancer risk, but that the 
      667T>C polymorphism is not.

PMID- 23976971
TI  - Proximal arterial occlusion in acute ischemic stroke with low NIHSS scores should
      not be considered as mild stroke.
AB  - BACKGROUND: Untreated acute mild stroke patients have substantial 90-day
      disability rates and worse outcomes than those who are treated with thrombolysis.
      There is little information regarding which patients with acute mild stroke will
      benefit from thrombolysis. We sought to investigate factors that are associated
      with early neurological deterioration (END) and poor prognosis in patients with
      acute mild stroke. METHODS: This was a retrospective study of consecutively
      registered patients with acute mild stroke (NIHSS <=3) at our tertiary stroke
      center between October 2008 and December 2011. END was defined as an increase in
      NIHSS >=2 points between hospital days 0 and 5. Modified Rankin Scale (mRS)
      scores of 0-1 at 90 days post-stroke were defined as favorable outcomes. RESULTS:
      A total of 378 (mean age, 65.9+/-13.0 years) patients were included in this
      study. END occurred in 55 patients (14.6%). IV-thrombolysis was performed in only
      9 patients. Symptomatic arterial occlusion on the initial MRA was independently
      associated with END (OR, 2.206; 95% CI, 1.219-3.994; p = 0.009) by multivariate
      logistic regression. Of the 119 patients with symptomatic arterial occlusion, ICA
      occlusion was independently associated with END (OR, 8.606; 95% CI, 2.312-32.043;
      p = 0.001). CONCLUSIONS: This study demonstrates that symptomatic arterial
      occlusion may be an important predictor of END in patients with acute mild
      stroke. It may therefore be important to consider that acute ischemic stroke with
      symptomatic arterial occlusion and low NIHSS scores may not represent mild stroke
      in acute periods.

PMID- 23976972
TI  - Association of the ephreceptor tyrosinekinase-type A2 (EPHA2) gene polymorphism
      rs3754334 with age-related cataract risk: a meta-analysis.
AB  - BACKGROUND: Recent clinical studies have assessed the association of various
      polymorphisms on the ephreceptor tyrosinekinase-type A2 (EPHA2) with the risk for
      age-related cataract in populations of different ethnic/racial backgrounds, but
      inconsistent results have been obtained. OBJECTIVE: This meta-analysis aimed to
      identify if any polymorphism(s) might be commonly present in different
      ethnic/racial populations in association with the age-related cataract risk.
      METHODS: The PubMed and Web of Science databases (up to December 1, 2012) were
      searched for clinical studies on the association of EPHA2 polymorphisms with the
      risk for age-related cataract. The polymorphisms that were assessed in all
      eligible studies were analyzed for their association with the risk for age
      related cataract using different models. RESULTS: Three studies were identified,
      which were conducted, respectively, on white Americans in the Unites States and
      on Asians in Indian and China. The polymorphism, rs3754334, was the only one
      studied in all these three studies and was therefore the focus of this meta
      analysis. No publication bias or heterogeneity was found. Our analysis results
      demonstrated that rs3754334 was associated with the risk of any cataracts in the
      recessive (OR = 1.202, 95% CI: 1.051-1.375, P = 0.007) and Codominant (OR =
      1.194, 95% CI: 1.035-1.378, P = 0.015) models, but its association with cortical
      or nuclear phenotype of age-related cataract was not evident. CONCLUSION:
      Polymorphism, rs3754334, might be a variant on the EPHA2 gene that is commonly
      associated with the risk for age-related cataract in different ethnical and
      geographical populations.

PMID- 23976973
TI  - p53 increases intra-cellular calcium release by transcriptional regulation of
      calcium channel TRPC6 in GaQ3-treated cancer cells.
AB  - p53 and calcium signaling are inter-dependent and are known to show both
      synergistic and antagonistic effects on each other in the cellular environment.
      However, no molecular mechanism or cellular pathway is known which shows direct
      regulation between these important cellular signaling molecules. Here we have
      shown that in cancer cells treated with anti-neoplastic drug GaQ3, p53, there is
      an increase in intracellular calcium levels by transcriptional regulation of a
      novel calcium channel gene TRPC6. p53 directly binds to a 22 bp response element
      in the TRPC6 gene promoter and increase its mRNA and protein expression. Over
      expression of TRPC6 results in calcium-dependent apoptotic death and activation
      of apoptotic genes in a variety of cancer cells. This research work shows that
      p53 and its transcriptional activity is critical in regulation of calcium
      signaling and an increase in the intracellular calcium level might be one of the
      anti-cancer strategies to induce apoptosis in cancer cells. 

PMID- 23976974
TI  - Lactotransferrin in Asian elephant (Elephas maximus) seminal plasma correlates
      with semen quality.
AB  - Asian elephants (Elephas maximus) have highly variable ejaculate quality within
      individuals, greatly reducing the efficacy of artificial insemination and making
      it difficult to devise a sperm cryopreservation protocol for this endangered
      species. Because seminal plasma influences sperm function and physiology,
      including sperm motility, the objectives of this study were to characterize the
      chemistry and protein profiles of Asian elephant seminal plasma and to determine
      the relationships between seminal plasma components and semen quality. Ejaculates
      exhibiting good sperm motility (>=65%) expressed higher percentages of
      spermatozoa with normal morphology (80.3+/-13.0 vs. 44.9+/-30.8%) and positive
      Spermac staining (51.9+/-14.5 vs. 7.5+/-14.4%), in addition to higher total
      volume (135.1+/-89.6 vs. 88.8+/-73.1 ml) and lower sperm concentration (473.0+/
      511.2 vs. 1313.8+/-764.7*106 cells ml-1) compared to ejaculates exhibiting poor
      sperm motility (<=10%; P<0.05). Comparison of seminal plasma from ejaculates with
      good versus poor sperm motility revealed significant differences in
      concentrations of creatine phosphokinase, alanine aminotransferase, phosphorus,
      sodium, chloride, magnesium, and glucose. These observations suggest seminal
      plasma influences semen quality in elephants. One- and two-dimensional (2D) gel
      electrophoresis revealed largely similar compositional profiles of seminal plasma
      proteins between good and poor motility ejaculates. However, a protein of ~80 kDa
      was abundant in 85% of ejaculates with good motility, and was absent in 90% of
      poor motility ejaculates (P<0.05). We used mass spectrometry to identify this
      protein as lactotransferrin, and immunoblot analysis to confirm this
      identification. Together, these findings lay a functional foundation for
      understanding the contributions of seminal plasma in the regulation of Asian
      elephant sperm motility, and for improving semen collection and storage in this
      endangered species.

PMID- 23976975
TI  - T4 phage and its head surface proteins do not stimulate inflammatory mediator
      production.
AB  - Viruses are potent activators of the signal pathways leading to increased
      cytokine or ROS production. The effects exerted on the immune system are usually
      mediated by viral proteins. Complementary to the progress in phage therapy
      practice, advancement of knowledge about the influence of bacteriophages on
      mammalian immunity is necessary. Particularly, the potential ability of phage
      proteins to act like other viral stimulators of the immune system may have strong
      practical implications for the safety and efficacy of bacteriophage therapy. Here
      we present studies on the effect of T4 phage and its head proteins on production
      of inflammatory mediators and inflammation-related factors: IL-1alpha, IL-1beta,
      IL-2, IL-6, IL-10, IL-12 p40/p70, IFN-gamma, TNF-alpha, MCP-1, MIG, RANTES, GCSF,
      GM-CSF and reactive oxygen species (ROS). Plasma cytokine profiles in an in vivo
      mouse model and in human blood cells treated with gp23*, gp24*, Hoc and Soc were
      evaluated by cytokine antibody arrays. Cytokine production and expression of
      CD40, CD80, CD86 and MHC class II molecules were also investigated in mouse bone
      marrow-derived dendritic cells treated with whole T4 phage particle or the same
      capsid proteins. The influence of T4 and gp23*, gp24*, Hoc and Soc on reactive
      oxygen species generation was examined in blood cells using luminol-dependent
      chemiluminescence assay. In all performed assays, the T4 bacteriophage and its
      capsid proteins gp23*, gp24*, Hoc and Soc did not affect production of
      inflammatory-related cytokines or ROS. These observations are of importance for
      any medical or veterinary application of bacteriophages. 

PMID- 23976976
TI  - Development of in situ gelling and bio adhesive 5-Fluorouracil enema.
AB  - In this study, a novel 5-Fluorouracil (5-FU) enema with good bio adhesion and
      temperature sensitivity was developed using in situ gelling technology. The
      preparation was formulated as a free-flowing liquid before use, while a layer of
      gel film was quickly formed when administered in the rectum, with a large contact
      surface area. It also demonstrated good biocompatibility, appropriate gel
      strength and bio adhesive force with excellent adhesion to rectal mucosa and
      prolonged action time, allowing more effective drug absorption and diffusion to
      surrounding tissues. Poloxamer 407 and poloxamer 188 were applied to adjust the
      gelling temperature. With the addition of carbopol and polycarbophil (bio
      adhesive substances), the solubility of 5-FU and gel strength increased, the
      temperature of gelation and the surface area of drug contact on mucous epithelium
      decreased. Decreased adhesive force between the preparation and the mucous
      membrane of the rectum was demonstrated with improving carbopol and
      polycarbophil's concentration. In vitro release demonstrated that 5-FU in situ
      gelling enema with different bases had a rapid and almost complete drug release.
      We used an optimized formulation of P407/P188/polycarbophil/5-FU (17/2.5/0.2/1.0)
      for animal experiments. The result showed that the drug evenly covered the
      surface of the rectum and there was no leakage in 6 hours. The in situ gelling
      enema showed significantly higher rectal tissue levels of 5-FU compared with
      suppository and intravenous administration, indicating that 5-FU could be well
      absorbed due to the enlarged releasing area, longer retention time and larger
      amount of dissolved active ingredients. Systemically, 5-FU levels in the enema
      group were similar to those in the suppository group and significantly lower than
      the intravenous group. The enema was not associated with morphological damage to
      rectal tissue. These results suggest that the bio adhesive and in situ gelling
      enema could be a more effective rectal delivery system of 5-FU. 

PMID- 23976978
TI  - HVEM gene polymorphisms are associated with sporadic breast cancer in Chinese
      women.
AB  - As a costimulatory molecule, Herpesvirus entry mediator (HVEM) can bind with
      several costimulatory members, thus HVEM plays different roles in T cell
      immunity. HVEM and its ligands have been involved in the pathogenesis of various
      autoimmune, inflammatory diseases and tumors. In the current study, we conducted
      a case-control study comparing polymorphisms of HVEM and breast cancer. Subjects
      included 575 females with breast cancer and 604 age-matched healthy controls. Six
      HVEM SNPs (rs2281852, rs1886730, rs2234163, rs11573979, rs2234165, and rs2234167)
      were genotyped by PCR-RFLP. The results showed significant differences in
      genotypes and alleles between rs1886730 and rs2234167 (P<0.05). One haplotype
      (CTGCGG) that was associated with breast cancer was found via haplotype analysis.
      Our research also indicated an association between polymorphisms of HVEM and
      clinicopathologic features, including lymph node metastasis, estrogen receptor,
      progesterone receptor and P53. Our results primarily indicate that polymorphisms
      of the HVEM gene were associated with the risk of sporadic breast cancer in
      northeast Chinese females. 

PMID- 23976979
TI  - The rediscovery of a long described species reveals additional complexity in
      speciation patterns of poeciliid fishes in sulfide springs.
AB  - The process of ecological speciation drives the evolution of locally adapted and
      reproductively isolated populations in response to divergent natural selection.
      In Southern Mexico, several lineages of the freshwater fish species of the genus
      Poecilia have independently colonized toxic, hydrogen sulfide-rich springs. Even
      though ecological speciation processes are increasingly well understood in this
      system, aligning the taxonomy of these fish with evolutionary processes has
      lagged behind. While some sulfide spring populations are classified as ecotypes
      of Poecilia mexicana, others, like P. sulphuraria, have been described as highly
      endemic species. Our study particularly focused on elucidating the taxonomy of
      the long described sulfide spring endemic, Poecilia thermalis Steindachner 1863,
      and investigates if similar evolutionary patterns of phenotypic trait divergence
      and reproductive isolation are present as observed in other sulfidic species of
      Poecilia. We applied a geometric morphometric approach to assess body shape
      similarity to other sulfidic and non-sulfidic fish of the genus Poecilia. We also
      conducted phylogenetic and population genetic analyses to establish the
      phylogenetic relationships of P. thermalis and used a population genetic approach
      to determine levels of gene flow among Poecilia from sulfidic and non-sulfidic
      sites. Our results indicate that P. thermalis' body shape has evolved in
      convergence with other sulfide spring populations in the genus. Phylogenetic
      analyses placed P. thermalis as most closely related to one population of P.
      sulphuraria, and population genetic analyses demonstrated that P. thermalis is
      genetically isolated from both P. mexicana ecotypes and P. sulphuraria. Based on
      these findings, we make taxonomic recommendations for P. thermalis. Overall, our
      study verifies the role of hydrogen sulfide as a main factor shaping convergent,
      phenotypic evolution and the emergence of reproductive isolation between Poecilia
      populations residing in adjacent sulfidic and non-sulfidic environments. 

PMID- 23976977
TI  - Extinction of hepatitis C virus by ribavirin in hepatoma cells involves lethal
      mutagenesis.
AB  - Lethal mutagenesis, or virus extinction produced by enhanced mutation rates, is
      under investigation as an antiviral strategy that aims at counteracting the
      adaptive capacity of viral quasispecies, and avoiding selection of antiviral
      escape mutants. To explore lethal mutagenesis of hepatitis C virus (HCV), it is
      important to establish whether ribavirin, the purine nucleoside analogue used in
      anti-HCV therapy, acts as a mutagenic agent during virus replication in cell
      culture. Here we report the effect of ribavirin during serial passages of HCV in
      human hepatoma Huh-7.5 cells, regarding viral progeny production and complexity
      of mutant spectra. Ribavirin produced an increase of mutant spectrum complexity
      and of the transition types associated with ribavirin mutagenesis, resulting in
      HCV extinction. Ribavirin-mediated depletion of intracellular GTP was not the
      major contributory factor to mutagenesis since mycophenolic acid evoked a similar
      decrease in GTP without an increase in mutant spectrum complexity. The
      intracellular concentration of the other nucleoside-triphosphates was elevated as
      a result of ribavirin treatment. Mycophenolic acid extinguished HCV without an
      intervening mutagenic activity. Ribavirin-mediated, but not mycophenolic acid
      mediated, extinction of HCV occurred via a decrease of specific infectivity, a
      feature typical of lethal mutagenesis. We discuss some possibilities to explain
      disparate results on ribavirin mutagenesis of HCV. 

PMID- 23976980
TI  - Does raising type 1 error rate improve power to detect interactions in linear
      regression models? A simulation study.
AB  - INTRODUCTION: Statistical interactions are a common component of data analysis
      across a broad range of scientific disciplines. However, the statistical power to
      detect interactions is often undesirably low. One solution is to elevate the Type
      1 error rate so that important interactions are not missed in a low power
      situation. To date, no study has quantified the effects of this practice on power
      in a linear regression model. METHODS: A Monte Carlo simulation study was
      performed. A continuous dependent variable was specified, along with three types
      of interactions: continuous variable by continuous variable; continuous by
      dichotomous; and dichotomous by dichotomous. For each of the three scenarios, the
      interaction effect sizes, sample sizes, and Type 1 error rate were varied,
      resulting in a total of 240 unique simulations. RESULTS: In general, power to
      detect the interaction effect was either so low or so high at alpha = 0.05 that
      raising the Type 1 error rate only served to increase the probability of
      including a spurious interaction in the model. A small number of scenarios were
      identified in which an elevated Type 1 error rate may be justified. CONCLUSIONS:
      Routinely elevating Type 1 error rate when testing interaction effects is not an
      advisable practice. Researchers are best served by positing interaction effects a
      priori and accounting for them when conducting sample size calculations.

PMID- 23976981
TI  - Phenyl acyl acids attenuate the unfolded protein response in tunicamycin-treated
      neuroblastoma cells.
AB  - Understanding how neural cells handle proteostasis stress in the endoplasmic
      reticulum (ER) is important to decipher the mechanisms that underlie the cell
      death associated with neurodegenerative diseases and to design appropriate
      therapeutic tools. Here we have compared the sensitivity of a human neuroblastoma
      cell line (SH-SY5H) to the ER stress caused by an inhibitor of protein
      glycosylation with that observed in human embryonic kidney (HEK-293T) cells. In
      response to stress, SH-SY5H cells increase the expression of mRNA encoding
      downstream effectors of ER stress sensors and transcription factors related to
      the unfolded protein response (the spliced X-box binding protein 1, CCAAT
      enhancer-binding protein homologous protein, endoplasmic reticulum-localized DnaJ
      homologue 4 and asparagine synthetase). Tunicamycin-induced death of SH-SY5H
      cells was prevented by terminal aromatic substituted butyric or valeric acids, in
      association with a decrease in the mRNA expression of stress-related factors, and
      in the accumulation of the ATF4 protein. Interestingly, this decrease in ATF4
      protein occurs without modifying the phosphorylation of the translation
      initiation factor eIF2alpha. Together, these results show that when short chain
      phenyl acyl acids alleviate ER stress in SH-SY5H cells their survival is
      enhanced. 

PMID- 23976982
TI  - Genomic profiling reveals that transient adipogenic activation is a hallmark of
      mouse models of skeletal muscle regeneration.
AB  - The marbling of skeletal muscle by ectopic adipose tissue is a hallmark of many
      muscle diseases, including sarcopenia and muscular dystrophies, and generally
      associates with impaired muscle regeneration. Although the etiology and the
      molecular mechanisms of ectopic adipogenesis are poorly understood, fatty
      regeneration can be modeled in mice using glycerol-induced muscle damage. Using
      comprehensive molecular and histological profiling, we compared glycerol-induced
      fatty regeneration to the classical cardiotoxin (CTX)-induced regeneration model
      previously believed to lack an adipogenic response in muscle. Surprisingly,
      ectopic adipogenesis was detected in both models, but was stronger and more
      persistent in response to glycerol. Importantly, extensive differential
      transcriptomic profiling demonstrated that glycerol induces a stronger
      inflammatory response and promotes adipogenic regulatory networks while reducing
      fatty acid beta-oxidation. Altogether, these results provide a comprehensive
      mapping of gene expression changes during the time course of two muscle
      regeneration models, and strongly suggest that adipogenic commitment is a
      hallmark of muscle regeneration, which can lead to ectopic adipocyte accumulation
      in response to specific physio-pathological challenges. 

PMID- 23976983
TI  - Bacteriuria amongst pregnant women in the Buea Health District, Cameroon:
      prevalence, predictors, antibiotic susceptibility patterns and diagnosis.
AB  - BACKGROUND: Bacteriuria is associated with significant maternal and foetal risks.
      However, its prevalence is not known in our community. OBJECTIVES: This study was
      carried out to determine the prevalence and predictors of bacteriuria in pregnant
      women of the Buea Health District (BHD) as well as the antibiotic sensitivity
      patterns of bacterial isolates. It also sought to determine the diagnostic
      performance of the nitrite and leucocyte esterase tests in detecting bacteriuria
      in these women. METHODS: An observational analytic cross-sectional study was
      carried out amongst pregnant women attending selected antenatal care centres in
      Buea. We recruited 102 consenting pregnant women for the study. Demographic and
      clinical data were collected using structured questionnaires. Clean catch
      midstream urine was collected from each participant in sterile leak proof
      containers. Samples were examined biochemically, microscopically and by culture.
      Significant bacteriuria was defined as the presence of >=108 bacteria/L of
      cultured urine. Identification and susceptibility of isolates was performed using
      API 20E and ATB UR EU (08) (BioMerieux, Marcy l'Etoile, France). RESULTS:
      Significant bacteriuria was found in the urine of 24 of the 102 women tested
      giving a bacteriuria prevalence of 23.5% in pregnant women of the BHD.
      Asymptomatic bacteriuria was detected in 8(7.8%) of the women. There was no
      statistically significant predictor of bacteriuria. Escherichia coli were the
      most isolated (33%) uropathogens and were 100% sensitive to cefixime, cefoxitin
      and cephalothin. The nitrite and leucocyte esterase tests for determining
      bacteriuria had sensitivities of 8%, 20.8% and specificities of 98.7% and 80.8%
      respectively. CONCLUSION: Bacteriuria is frequent in pregnant women in the BHD
      suggesting the need for routine screening by urine culture. Empiric treatment
      with cefixime should be instituted until results of urine culture and sensitivity
      are available. Nitrite and leucocyte esterase tests were not sensitive enough to
      replace urine culture as screening tests.

PMID- 23976984
TI  - ApoER2 and VLDLr are required for mediating reelin signalling pathway for normal
      migration and positioning of mesencephalic dopaminergic neurons.
AB  - The migration of mesencephalic dopaminergic (mDA) neurons from the subventricular
      zone to their final positions in the substantia nigra compacta (SNc), ventral
      tegmental area (VTA), and retrorubral field (RRF) is controlled by signalling
      from neurotrophic factors, cell adhesion molecules (CAMs) and extracellular
      matrix molecules (ECM). Reelin and the cytoplasmic adaptor protein Disabled-1
      (Dab1) have been shown to play important roles in the migration and positioning
      of mDA neurons. Mice lacking Reelin and Dab1 both display phenotypes
      characterised by the failure of nigral mDA neurons to migrate properly. ApoER2
      and VLDLr are receptors for Reelin signalling and are therefore part of the same
      signal transduction pathway as Dab1. Here we describe the roles of ApoER2 and
      VLDLr in the proper migration and positioning of mDA neurons in mice. Our results
      demonstrate that VLDLr- and ApoER2-mutant mice have both a reduction in and
      abnormal positioning of mDA neurons. This phenotype was more pronounced in VLDLr
      mutant mice. Moreover, we provide evidence that ApoER2/VLDLr double-knockout mice
      show a phenotype comparable with the phenotypes observed for Reelin- and Dab1-
      mutant mice. Taken together, our results demonstrate that the Reelin receptors
      ApoER2 and VLDLr play essential roles in Reelin-mediated migration and
      positioning of mDA neurons. 

PMID- 23976985
TI  - Inhibition of the growth factor MDK/midkine by a novel small molecule compound to
      treat non-small cell lung cancer.
AB  - Midkine (MDK) is a heparin-binding growth factor that is highly expressed in many
      malignant tumors, including lung cancers. MDK activates the PI3K pathway and
      induces anti-apoptotic activity, in turn enhancing the survival of tumors.
      Therefore, the inhibition of MDK is considered a potential strategy for cancer
      therapy. In the present study, we demonstrate a novel small molecule compound
      (iMDK) that targets MDK. iMDK inhibited the cell growth of MDK-positive H441 lung
      adenocarcinoma cells that harbor an oncogenic KRAS mutation and H520 squamous
      cell lung cancer cells, both of which are types of untreatable lung cancer.
      However, iMDK did not reduce the cell viability of MDK-negative A549 lung
      adenocarcinoma cells or normal human lung fibroblast (NHLF) cells indicating its
      specificity. iMDK suppressed the endogenous expression of MDK but not that of
      other growth factors such as PTN or VEGF. iMDK suppressed the growth of H441
      cells by inhibiting the PI3K pathway and inducing apoptosis. Systemic
      administration of iMDK significantly inhibited tumor growth in a xenograft mouse
      model in vivo. Inhibition of MDK with iMDK provides a potential therapeutic
      approach for the treatment of lung cancers that are driven by MDK. 

PMID- 23976986
TI  - Substitution p.A350V in Na+/Mg2+ exchanger SLC41A1, potentially associated with
      Parkinson's disease, is a gain-of-function mutation.
AB  - Parkinson's disease (PD) is a complex multifactorial ailment predetermined by the
      interplay of various environmental and genetic factors. Systemic and
      intracellular magnesium (Mg) deficiency has long been suspected to contribute to
      the development and progress of PD and other neurodegenerative diseases. However,
      the molecular background is unknown. Interestingly, gene SLC41A1 located in the
      novel PD locus PARK16 has recently been identified as being a Na+/Mg2+ exchanger
      (NME, Mg2+ efflux system), a key component of cellular magnesium homeostasis.
      Here, we demonstrate that the substitution p.A350V potentially associated with PD
      is a gain-of-function mutation that enhances a core function of SLC41A1, namely
      Na+-dependent Mg2+ efflux by 69+/-10% under our experimental conditions (10
      minute incubation in high-Na+ (145 mM) and completely Mg2+-free medium). The
      increased efflux capacity is accompanied by an insensitivity of mutant NME to
      cAMP stimulation suggesting disturbed hormonal regulation and leads to a reduced
      proliferation rate in p.A350V compared with wt cells. We hypothesize that
      enhanced Mg2+-efflux conducted by SLC41A1 variant p.A350V might result, in the
      long-term, in chronic intracellular Mg2+-deficiency, a condition that is found in
      various brain regions of PD patients and that exacerbates processes triggering
      neuronal damage.

PMID- 23976987
TI  - Synapto-protective drugs evaluation in reconstructed neuronal network.
AB  - Chronic neurodegenerative syndromes such as Alzheimer's and Parkinson's diseases,
      or acute syndromes such as ischemic stroke or traumatic brain injuries are
      characterized by early synaptic collapse which precedes axonal and neuronal cell
      body degeneration and promotes early cognitive impairment in patients. Until now,
      neuroprotective strategies have failed to impede the progression of
      neurodegenerative syndromes. Drugs preventing the loss of cell body do not
      prevent the cognitive decline, probably because they lack synapto-protective
      effects. The absence of physiologically realistic neuronal network models which
      can be easily handled has hindered the development of synapto-protective drugs
      suitable for therapies. Here we describe a new microfluidic platform which makes
      it possible to study the consequences of axonal trauma of reconstructed oriented
      mouse neuronal networks. Each neuronal population and sub-compartment can be
      chemically addressed individually. The somatic, mid axon, presynaptic and
      postsynaptic effects of local pathological stresses or putative protective
      molecules can thus be evaluated with the help of this versatile "brain on chip"
      platform. We show that presynaptic loss is the earliest event observed following
      axotomy of cortical fibers, before any sign of axonal fragmentation or post
      synaptic spine alteration. This platform can be used to screen and evaluate the
      synapto-protective potential of several drugs. For instance, NAD+ and the Rho
      kinase inhibitor Y27632 can efficiently prevent synaptic disconnection, whereas
      the broad-spectrum caspase inhibitor zVAD-fmk and the stilbenoid resveratrol do
      not prevent presynaptic degeneration. Hence, this platform is a promising tool
      for fundamental research in the field of developmental and neurodegenerative
      neurosciences, and also offers the opportunity to set up pharmacological
      screening of axon-protective and synapto-protective drugs.

PMID- 23976988
TI  - The effects of shift work on sleeping quality, hypertension and diabetes in
      retired workers.
AB  - BACKGROUND: Shift work has been associated with adverse health effects by
      disturbing circadian rhythms. However,its potential long-term health effects and
      the persistent effects after leaving shifts have not been well established.
      METHODS AND RESULTS: We studied 26,463 workers from Tongji-Dongfeng Cohort in
      China. All the participants are retired employees of Dongfeng Motor Company.
      Information on demographics, occupational history and medical history were
      gathered through questionnaires. After adjusting potential confounders in the
      logistic regression models, shift work was associated with poor sleeping quality,
      diabetes and hypertension independently. We observed significant effects of shift
      work on poor sleeping quality, diabetes and hypertension; the ORs (95%CI) are
      1.18 (1.09-1.27), 1.10 (1.03-1.17) and 1.05 (1.01-1.09) respectively. In the
      further analysis, we found elevated ORs (95%CI) for participants with poor
      sleeping quality, the ORs (95%CI) are 1.34 (1.08-1.60), 1.13 (1.05-1.21), 1.05
      (1.03-1.07) and 1.05 (1.01-1.09) for 1-4, 5-9, 10-19, >=20 years of shift work
      respectively. However, with the extension of leaving shift work duration, the
      effects of shift work on sleep quality gradually reduced. CONCLUSIONS: Shift work
      may be an independent risk factor for sleeping quality, diabetes and hypertension
      even in retired workers. Applicable intervention strategies are needed for
      prevention of sleep loss, diabetes, and hypertension for shift workers.

PMID- 23976989
TI  - Overexpression of the toll-like receptor (TLR) signaling adaptor MYD88, but lack
      of genetic mutation, in myelodysplastic syndromes.
AB  - MYD88 is a key mediator of Toll-like receptor innate immunity signaling.
      Oncogenically active MYD88 mutations have recently been reported in lymphoid
      malignancies, but has not been described in MDS. To characterize MYD88 in MDS, we
      sequenced the coding region of the MYD88 gene in 40 MDS patients. No MYD88
      mutation was detected. We next characterized MYD88 expression in bone marrow
      CD34+ cells (N = 64). Increased MYD88 RNA was detected in 40% of patients.
      Patients with higher MYD88 expression in CD34+ cells had a tendency for shorter
      survival compared to the ones with lower MYD88, which was significant when
      controlled for IPSS and age. We then evaluated effect of MYD88 blockade in the
      CD34+ cells of patients with lower-risk MDS. Colony formation assays indicated
      that MYD88 blockade using a MYD88 inhibitor resulted in increased erythroid
      colony formation. MYD88 blockade also negatively regulated the secretion of
      interleukin-8. Treatment of MDS CD34+ cells with an IL-8 antibody also increased
      formation of erythroid colonies. These results indicate that MYD88 plays a role
      in the pathobiology of MDS and may have prognostic and therapeutic value in the
      management of patients with this disease. 

PMID- 23976990
TI  - Photosynthetic electron transport system promotes synthesis of Au-nanoparticles.
AB  - In this communication, a novel, green, efficient and economically viable light
      mediated protocol for generation of Au-nanoparticles using most vital organelle,
      chloroplasts, of the plant system is portrayed. Thylakoids/chloroplasts isolated
      from Potamogeton nodosus (an aquatic plant) and Spinacia oleracea (a terrestrial
      plant) turned Au3+ solutions purple in presence of light of 600 umol m-2 s-1
      photon flux density (PFD) and the purple coloration intensified with time. UV-Vis
      spectra of these purple colored solutions showed absorption peak at ~545 nm which
      is known to arise due to surface plasmon oscillations specific to Au
      nanoparticles. However, thylakoids/chloroplasts did not alter color of Au3+
      solutions in dark. These results clearly demonstrated that photosynthetic
      electron transport can reduce Au3+ to Au0 which nucleate to form Au-nanoparticles
      in presence of light. Transmission electron microscopic studies revealed that Au
      nanoparticles generated by light driven photosynthetic electron transport system
      of thylakoids/chloroplasts were in range of 5-20 nm. Selected area electron
      diffraction and powder X-ray diffraction indicated crystalline nature of these
      nanoparticles. Energy dispersive X-ray confirmed that these nanoparticles were
      composed of Au. To confirm the potential of light driven photosynthetic electron
      transport in generation of Au-nanoparticles, thylakoids/chloroplasts were tested
      for their efficacy to generate Au-nanoparticles in presence of light of PFD
      ranging from 60 to 600 umol m-2 s-1. The capacity of thylakoids/chloroplasts to
      generate Au-nanoparticles increased remarkably with increase in PFD, which
      further clearly demonstrated potential of light driven photosynthetic electron
      transport in reduction of Au3+ to Au0 to form nanoparticles. The light driven
      donation of electrons to metal ions by thylakoids/chloroplasts can be exploited
      for large scale production of nanoparticles.

PMID- 23976991
TI  - Climate dynamics: a network-based approach for the analysis of global
      precipitation.
AB  - Precipitation is one of the most important meteorological variables for defining
      the climate dynamics, but the spatial patterns of precipitation have not been
      fully investigated yet. The complex network theory, which provides a robust tool
      to investigate the statistical interdependence of many interacting elements, is
      used here to analyze the spatial dynamics of annual precipitation over seventy
      years (1941-2010). The precipitation network is built associating a node to a
      geographical region, which has a temporal distribution of precipitation, and
      identifying possible links among nodes through the correlation function. The
      precipitation network reveals significant spatial variability with barely
      connected regions, as Eastern China and Japan, and highly connected regions, such
      as the African Sahel, Eastern Australia and, to a lesser extent, Northern Europe.
      Sahel and Eastern Australia are remarkably dry regions, where low amounts of
      rainfall are uniformly distributed on continental scales and small-scale extreme
      events are rare. As a consequence, the precipitation gradient is low, making
      these regions well connected on a large spatial scale. On the contrary, the
      Asiatic South-East is often reached by extreme events such as monsoons, tropical
      cyclones and heat waves, which can all contribute to reduce the correlation to
      the short-range scale only. Some patterns emerging between mid-latitude and
      tropical regions suggest a possible impact of the propagation of planetary waves
      on precipitation at a global scale. Other links can be qualitatively associated
      to the atmospheric and oceanic circulation. To analyze the sensitivity of the
      network to the physical closeness of the nodes, short-term connections are
      broken. The African Sahel, Eastern Australia and Northern Europe regions again
      appear as the supernodes of the network, confirming furthermore their long-range
      connection structure. Almost all North-American and Asian nodes vanish, revealing
      that extreme events can enhance high precipitation gradients, leading to a
      systematic absence of long-range patterns. 

PMID- 23976992
TI  - Deciphering the glycan preference of bacterial lectins by glycan array and
      molecular docking with validation by microcalorimetry and crystallography.
AB  - Recent advances in glycobiology revealed the essential role of lectins for
      deciphering the glycocode by specific recognition of carbohydrates. Integrated
      multiscale approaches are needed for characterizing lectin specificity: combining
      on one hand high-throughput analysis by glycan array experiments and systematic
      molecular docking of oligosaccharide libraries and on the other hand detailed
      analysis of the lectin/oligosaccharide interaction by x-ray crystallography,
      microcalorimetry and free energy calculations. The lectins LecB from Pseudomonas
      aeruginosa and BambL from Burkholderia ambifaria are part of the virulence
      factors used by the pathogenic bacteria to invade the targeted host. These two
      lectins are not related but both recognize fucosylated oligosaccharides such as
      the histo-blood group oligosaccharides of the ABH(O) and Lewis epitopes. The
      specificities were characterized using semi-quantitative data from glycan array
      and analyzed by molecular docking with the Glide software. Reliable prediction of
      protein/oligosaccharide structures could be obtained as validated by existing
      crystal structures of complexes. Additionally, the crystal structure of
      BambL/Lewis x was determined at 1.6 A resolution, which confirms that Lewis x has
      to adopt a high-energy conformation so as to bind to this lectin. Free energies
      of binding were calculated using a procedure combining the Glide docking protocol
      followed by free energy rescoring with the Prime/Molecular Mechanics Generalized
      Born Surface Area (MM-GBSA) method. The calculated data were in reasonable
      agreement with experimental free energies of binding obtained by titration
      microcalorimetry. The established predictive protocol is proposed to rationalize
      large sets of data such as glycan arrays and to help in lead discovery projects
      based on such high throughput technology. 

PMID- 23976993
TI  - Fibrin clot structure and platelet aggregation in patients with aspirin treatment
      failure.
AB  - BACKGROUND: Aspirin is a cornerstone in prevention of cardiovascular events and
      modulates both platelet aggregation and fibrin clot formation. Some patients
      experience cardiovascular events whilst on aspirin, often termed aspirin
      treatment failure (ATF). This study evaluated both platelet aggregation and
      fibrin clot structure in patients with ATF. METHODS: We included 177 stable
      coronary artery disease patients on aspirin monotherapy. Among these, 116 (66%)
      had ATF defined as myocardial infarction (MI) whilst on aspirin. Platelet
      aggregation was assessed by Multiplate(r) aggregometry and VerifyNow(r), whereas
      turbidimetric assays and scanning electron microscopy were employed to study
      fibrin clot characteristics. RESULTS: Enhanced platelet aggregation was observed
      in patients with ATF compared with non-MI patients following stimulation with
      arachidonic acid 1.0 mM (median 161 (IQR 95; 222) vs. 97 (60; 1776) AU*min, p =
      0.005) and collagen 1.0 ug/mL (293 (198; 427) vs. 220 (165; 370) AU*min, p =
      0.03). Similarly, clot maximum absorbance, a measure of fibrin network density,
      was increased in patients with ATF (0.48 (0.41; 0.52) vs. 0.42 (0.38; 0.50), p =
      0.02), and this was associated with thinner fibres (mean +/- SD: 119.7+/-27.5 vs.
      127.8+/-31.1 nm, p = 0.003) and prolonged lysis time (552 (498; 756) vs. 519
      (468; 633) seconds; p = 0.02). Patients with ATF also had increased levels of C
      reactive protein (CRP) (1.34 (0.48; 2.94) and 0.88 (0.32; 1.77) mg/L, p = 0.01)
      compared with the non-MI group. Clot maximum absorbance correlated with platelet
      aggregation (r = 0.31-0.35, p-values<0.001) and CRP levels (r = 0.60, p<0.001).
      CONCLUSIONS: Patients with aspirin treatment failure showed increased platelet
      aggregation and altered clot structure with impaired fibrinolysis compared with
      stable CAD patients without previous MI. These findings suggest that an increased
      risk of aspirin treatment failure may be identified by measuring both platelet
      function and fibrin clot structure.

PMID- 23976994
TI  - On the measurement of ecological novelty: scale-eating pupfish are separated by
      168 my from other scale-eating fishes.
AB  - The colonization of new adaptive zones is widely recognized as one of the
      hallmarks of adaptive radiation. However, the adoption of novel resources during
      this process is rarely distinguished from phenotypic change because morphology is
      a common proxy for ecology. How can we quantify ecological novelty independent of
      phenotype? Our study is split into two parts: we first document a remarkable
      example of ecological novelty, scale-eating (lepidophagy), within a rapidly
      evolving adaptive radiation of Cyprinodon pupfishes on San Salvador Island,
      Bahamas. This specialized predatory niche is known in several other fish groups,
      but is not found elsewhere among the 1,500 species of atherinomorphs. Second, we
      quantify this ecological novelty by measuring the time-calibrated phylogenetic
      distance in years to the most closely-related species with convergent ecology. We
      find that scale-eating pupfish are separated by 168 million years of evolution
      from the nearest scale-eating fish. We apply this approach to a variety of
      examples and highlight the frequent decoupling of ecological novelty from
      phenotypic divergence. We observe that novel ecology is not always tightly
      correlated with rates of phenotypic or species diversification, particularly
      within recent adaptive radiations, necessitating the use of additional measures
      of ecological novelty independent of phenotype. 

PMID- 23976995
TI  - Phloroglucinol attenuates motor functional deficits in an animal model of
      Parkinson's disease by enhancing Nrf2 activity.
AB  - In this study, we investigated whether phloroglucinol (1,3,5-trihydroxybenzene)
      has therapeutic effects in cellular and animal model of Parkinson's disease (PD).
      PD is the second most common, chronic and progressive neurodegenerative disease,
      and is clinically characterized with motor dysfunctions such as bradykinesia,
      rigidity, postural instability, gait impairment, and resting tremor. In the
      brains of PD patients, dopaminergic neuronal loss is observed in the Substantia
      nigra. Although the exact mechanisms underlying PD are largely unknown,
      mitochondrial dysfunction and oxidative stress are thought to be critical factors
      that induce the onset of the disease. Here, phloroglucinol administration was
      shown to attenuate motor functional deficits evaluated with rota-rod and
      apomorphine-induced rotation tests in 6-hydroxydopamine (6-OHDA)-induced PD
      animal models. Moreover, phloroglucinol ameliorated the loss of synapses as
      assessed with protein levels and immunoreactivity against synaptophysin in the
      midbrain region of the 6-OHDA-lesioned rats. In addition, in SH-SY5Y cultures,
      the cytotoxicity of 6-OHDA was reduced by pre-treatment with phloroglucinol. The
      increase in the reactive oxygen species, lipid peroxidation, protein carbonyl
      formation and 8-hydroxyguanine caused by treatment with 6-OHDA was attenuated by
      phloroglucinol in SH-SY5Y cells. Furthermore, phloroglucinol treatment rescued
      the reduced levels of nuclear Nrf2, antioxidant enzymes, i.e., catalase and
      glutathione peroxidase, in 6-OHDA-treated cells. Taken together, phloroglucinol
      has a therapeutic potential for treatment of PD.

PMID- 23976996
TI  - Establishment of mouse model of MYH9 disorders: heterozygous R702C mutation
      provokes macrothrombocytopenia with leukocyte inclusion bodies, renal
      glomerulosclerosis and hearing disability.
AB  - Nonmuscle myosin heavy chain IIA (NMMHCIIA) encoded by MYH9 is associated with
      autosomal dominantly inherited diseases called MYH9 disorders. MYH9 disorders are
      characterized by macrothrombocytopenia and very characteristic inclusion bodies
      in granulocytes. MYH9 disorders frequently cause nephritis, sensorineural hearing
      disability and cataracts. One of the most common and deleterious mutations
      causing these disorders is the R702C missense mutation. We generated knock-in
      mice expressing the Myh9 R702C mutation. R702C knock-in hetero mice (R702C+/-
      mice) showed macrothrombocytopenia. We studied megakaryopoiesis of cultured fetal
      liver cells of R702C+/- mice and found that proplatelet formation was impaired:
      the number of proplatelet tips was decreased, proplatelet size was increased, and
      proplatelet shafts were short and enlarged. Although granulocyte inclusion bodies
      were not visible by May-Grunwald Giemsa staining, immunofluorescence analysis
      indicated that NMMHCIIA proteins aggregated and accumulated in the granulocyte
      cytoplasm. In other organs, R702C+/- mice displayed albuminuria which increased
      with age. Renal pathology examination revealed glomerulosclerosis. Sensory
      hearing loss was indicated by lowered auditory brainstem response. These findings
      indicate that Myh9 R702C knock-in mice mirror features of human MYH9 disorders
      arising from the R702C mutation. 

PMID- 23976997
TI  - The common variant rs11646213 is associated with preeclampsia in Han Chinese
      women.
AB  - BACKGROUND: Preeclampsia, characterized by hypertension and proteinuria, is a
      multifactorial disease caused by complex interactions between environmental and
      genetic factors. A recent genome-wide association study of blood pressure
      reported an association between hypertension and rs11646213. This study evaluated
      the association between preeclampsia and rs11646213. METHODS: A total of 454
      cases and 460 controls were recruited to participate in this study. The single
      nucleotide polymorphism (SNP) rs11646213 was genotyped by polymerase chain
      reaction (PCR) and direct sequencing. RESULTS: The allele frequency of rs11646213
      was significantly different between the preeclampsia and control groups (P =
      0.017, OR = 1.36, 95% CI = 1.06-1.76). Differences were particularly significant
      in the severe preeclampsia subgroup (P = 0.002, OR = 1.54, 95% CI = 1.17-2.03)
      and the early-onset preeclampsia subgroup (P = 0.004, OR = 1.57, 95% CI = 1.16
      2.13). Genotyping analysis showed that the T allele of rs11646213 could confer a
      risk for preeclampsia, severe preeclampsia and early-onset preeclampsia.
      CONCLUSIONS: Rs11646213 upstream of the CDH13 gene is associated with
      preeclampsia in Han Chinese women.

PMID- 23976998
TI  - Differential gene expression in the brain of the African lungfish, Protopterus
      annectens, after six days or six months of aestivation in air.
AB  - The African lungfish, Protopterus annectens, can undergo aestivation during
      drought. Aestivation has three phases: induction, maintenance and arousal. The
      objective of this study was to examine the differential gene expression in the
      brain of P. annectens during the induction (6 days) and maintenance (6 months)
      phases of aestivation as compared with the freshwater control using suppression
      subtractive hybridization. During the induction phase of aestivation, the mRNA
      expression of prolactin (prl) and growth hormone were up-regulated in the brain
      of P. annectens, which indicate for the first time the possible induction role of
      these two hormones in aestivation. Also, the up-regulation of mRNA expression of
      tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma
      polypeptide and the down-regulation of phosphatidylethanolamine binding protein,
      suggest that there could be a reduction in biological and neuronal activities in
      the brain. The mRNA expression of cold inducible RNA-binding protein and glucose
      regulated protein 58 were also up-regulated in the brain, probably to enhance
      their cytoprotective effects. Furthermore, the down-regulation of prothymosin
      alpha expression suggests that there could be a suppression of transcription and
      cell proliferation in preparation for the maintenance phase. In general, the
      induction phase appeared to be characterized by reduction in glycolytic capacity
      and metabolic activity, suppression of protein synthesis and degradation, and an
      increase in defense against ammonia toxicity. In contrast, there was a down
      regulation in the mRNA expression of prl in the brain of P. annectens during the
      maintenance phase of aestivation. In addition, there could be an increase in
      oxidative defense capacity, and up-regulation of transcription, translation, and
      glycolytic capacities in preparation for arousal. Overall, our results signify
      the importance of reconstruction of protein structures and regulation of energy
      expenditure during the induction phase, and the needs to suppress protein
      degradation and conserve metabolic fuel stores during the maintenance phase of
      aestivation. 

PMID- 23976999
TI  - Tandem repeats, high copy number and remarkable diel expression rhythm of form II
      RuBisCO in Prorocentrum donghaiense (Dinophyceae).
AB  - Gene structure and expression regulation of form II RuBisCO (rbcII) in
      dinoflagellates are still poorly understood. Here we isolated this gene (Pdrbc)
      and investigated its diel expression pattern in a harmful algal bloom forming
      dinoflagellate Prorocentrum donghaiense. We obtained cDNA sequences with triple
      tandem repeats of the coding unit (CU); the 5' region has the sequence of a
      typical dinoflagellate plastid gene, encoding an N-terminus with two
      transmembrane regions separated by a plastid transit peptide. The CUs (1,455 bp
      except 1464 bp in last CU) are connected through a 63 bp spacer. Phylogenetic
      analysis showed that rbcII CUs within species formed monophyletic clusters,
      indicative of intraspecific gene duplication or purifying evolution. Using
      quantitative PCR (qPCR) we estimated 117+/-40 CUs of Pdrbc in the P. donghaiense
      genome. Although it is commonly believed that most dinoflagellate genes lack
      transcriptional regulation, our RT-qPCR analysis on synchronized cultures
      revealed remarkable diel rhythm of Pdrbc expression, showing significant
      correlations of transcript abundance with the timing of the dark-to-light
      transition and cell cycle G2M-phase. When the cultures were shifted to continuous
      light, Pdrbc expression remained significantly correlated with the G2M-phase.
      Under continuous darkness the cell cycle was arrested at the G1 phase, and the
      rhythm of Pdrbc transcription disappeared. Our results suggest that
      dinoflagellate rbcII 1) undergoes duplication or sequence purification within
      species, 2) is organized in tandem arrays in most species probably to facilitate
      efficient translation and import of the encoded enzyme, and 3) is regulated
      transcriptionally in a cell cycle-dependent fashion at least in some
      dinoflagellates. 

PMID- 23977000
TI  - A novel candidate vaccine for cytauxzoonosis inferred from comparative
      apicomplexan genomics.
AB  - Cytauxzoonosis is an emerging infectious disease of domestic cats (Felis catus)
      caused by the apicomplexan protozoan parasite Cytauxzoon felis. The growing
      epidemic, with its high morbidity and mortality points to the need for a
      protective vaccine against cytauxzoonosis. Unfortunately, the causative agent has
      yet to be cultured continuously in vitro, rendering traditional vaccine
      development approaches beyond reach. Here we report the use of comparative
      genomics to computationally and experimentally interpret the C. felis genome to
      identify a novel candidate vaccine antigen for cytauxzoonosis. As a starting
      point we sequenced, assembled, and annotated the C. felis genome and the proteins
      it encodes. Whole genome alignment revealed considerable conserved synteny with
      other apicomplexans. In particular, alignments with the bovine parasite Theileria
      parva revealed that a C. felis gene, cf76, is syntenic to p67 (the leading
      vaccine candidate for bovine theileriosis), despite a lack of significant
      sequence similarity. Recombinant subdomains of cf76 were challenged with survivor
      cat antiserum and found to be highly seroreactive. Comparison of eleven
      geographically diverse samples from the south-central and southeastern USA
      demonstrated 91-100% amino acid sequence identity across cf76, including a high
      level of conservation in an immunogenic 226 amino acid (24 kDa) carboxyl terminal
      domain. Using in situ hybridization, transcription of cf76 was documented in the
      schizogenous stage of parasite replication, the life stage that is believed to be
      the most important for development of a protective immune response. Collectively,
      these data point to identification of the first potential vaccine candidate
      antigen for cytauxzoonosis. Further, our bioinformatic approach emphasizes the
      use of comparative genomics as an accelerated path to developing vaccines against
      experimentally intractable pathogens. 

PMID- 23977001
TI  - The impact of telehealthcare on the quality and safety of care: a systematic
      overview.
AB  - BACKGROUND: Telehealthcare involves the use of information and communication
      technologies to deliver healthcare at a distance and to support patient self
      management through remote monitoring and personalised feedback. It is timely to
      scrutinise the evidence regarding the benefits, risks and costs of
      telehealthcare. METHODS AND FINDINGS: Two reviewers searched for relevant
      systematic reviews published from January 1997 to November 2011 in: The Cochrane
      Library, MEDLINE, EMBASE, LILACS, IndMed and PakMed. Reviewers undertook
      independent quality assessment of studies using the Critical Appraisal Skills
      Programme (CASP) tool for systematic reviews. 1,782 review articles were
      identified, from which 80 systematic reviews were selected for inclusion. These
      covered a range of telehealthcare models involving both synchronous (live) and
      asynchronous (store-and-forward) interactions between provider and patients. Many
      studies showed no differences in outcomes between telehealthcare and usual care.
      Several reviews highlighted the large number of short-term (<12 months)
      feasibility studies with under 20 participants. Effects of telehealthcare on
      health service indicators were reported in several reviews, particularly reduced
      hospitalisations. The reported clinical effectiveness of telehealthcare
      interventions for patients with long-term conditions appeared to be greatest in
      those with more severe disease at high-risk of hospitalisation and death. The
      failure of many studies to adequately describe the intervention makes it
      difficult to disentangle the contributions of technological and
      human/organisational factors on the outcomes reported. Evidence on the cost
      effectiveness of telehealthcare remains sparse. Patient safety considerations
      were absent from the evaluative telehealthcare literature. CONCLUSIONS:
      Policymakers and planners need to be aware that investment in telehealthcare will
      not inevitably yield clinical or economic benefits. It is likely that the
      greatest gains will be achieved for patients at highest risk of serious outcomes.
      There is a need for longer-term studies in order to determine whether the
      benefits demonstrated in time limited trials are sustained.

PMID- 23977002
TI  - Genome sequencing and analysis of BCG vaccine strains.
AB  - BACKGROUND: Although the Bacillus Calmette-Guerin (BCG) vaccine against
      tuberculosis (TB) has been available for more than 75 years, one third of the
      world's population is still infected with Mycobacterium tuberculosis and
      approximately 2 million people die of TB every year. To reduce this immense TB
      burden, a clearer understanding of the functional genes underlying the action of
      BCG and the development of new vaccines are urgently needed. METHODS AND
      FINDINGS: Comparative genomic analysis of 19 M. tuberculosis complex strains
      showed that BCG strains underwent repeated human manipulation, had higher region
      of deletion rates than those of natural M. tuberculosis strains, and lost several
      essential components such as T-cell epitopes. A total of 188 BCG strain T-cell
      epitopes were lost to various degrees. The non-virulent BCG Tokyo strain, which
      has the largest number of T-cell epitopes (359), lost 124. Here we propose that
      BCG strain protection variability results from different epitopes. This study is
      the first to present BCG as a model organism for genetics research. BCG strains
      have a very well-documented history and now detailed genome information. Genome
      comparison revealed the selection process of BCG strains under human manipulation
      (1908-1966). CONCLUSIONS: Our results revealed the cause of BCG vaccine strain
      protection variability at the genome level and supported the hypothesis that the
      restoration of lost BCG Tokyo epitopes is a useful future vaccine development
      strategy. Furthermore, these detailed BCG vaccine genome investigation results
      will be useful in microbial genetics, microbial engineering and other research
      fields.

PMID- 23977003
TI  - Allergen-induced dermatitis causes alterations in cutaneous retinoid-mediated
      signaling in mice.
AB  - Nuclear receptor-mediated signaling via RARs and PPARdelta is involved in the
      regulation of skin homeostasis. Moreover, activation of both RAR and PPARdelta
      was shown to alter skin inflammation. Endogenous all-trans retinoic acid (ATRA)
      can activate both receptors depending on specific transport proteins: Fabp5
      initiates PPARdelta signaling whereas Crabp2 promotes RAR signaling. Repetitive
      topical applications of ovalbumin (OVA) in combination with intraperitoneal
      injections of OVA or only intraperitoneal OVA applications were used to induce
      allergic dermatitis. In our mouse model, expression of IL-4, and Hbegf increased
      whereas expression of involucrin, Abca12 and Spink5 decreased in inflamed skin,
      demonstrating altered immune response and epidermal barrier homeostasis.
      Comprehensive gene expression analysis showed alterations of the cutaneous
      retinoid metabolism and retinoid-mediated signaling in allergic skin immune
      response. Notably, ATRA synthesis was increased as indicated by the elevated
      expression of retinaldehyde dehydrogenases and increased levels of ATRA.
      Consequently, the expression pattern of genes downstream to RAR was altered.
      Furthermore, the increased ratio of Fabp5 vs. Crabp2 may indicate an up
      regulation of the PPARdelta pathway in allergen-induced dermatitis in addition to
      the altered RAR signaling. Thus, our findings suggest that ATRA levels, RAR
      mediated signaling and signaling involved in PPARdelta pathways are mainly
      increased in allergen-induced dermatitis and may contribute to the development
      and/or maintenance of allergic skin diseases. 

PMID- 23977004
TI  - Exposure to cerium dioxide nanoparticles differently affect swimming performance
      and survival in two daphnid species.
AB  - The CeO2 NPs are increasingly used in industry but the environmental release of
      these NPs and their subsequent behavior and biological effects are currently
      unclear. This study evaluates for the first time the effects of CeO2 NPs on the
      survival and the swimming performance of two cladoceran species, Daphnia similis
      and Daphnia pulex after 1, 10 and 100 mg.L-1 CeO2 exposures for 48 h. Acute
      toxicity bioassays were performed to determine EC50 of exposed daphnids. Video
      recorded swimming behavior of both daphnids was used to measure swimming speeds
      after various exposures to aggregated CeO2 NPs. The acute ecotoxicity showed that
      D. similis is 350 times more sensitive to CeO2 NPs than D. pulex, showing 48-h
      EC50 of 0.26 mg.L-1 and 91.79 mg.L-1, respectively. Both species interacted with
      CeO2 NPs (adsorption), but much more strongly in the case of D. similis. Swimming
      velocities (SV) were differently and significantly affected by CeO2 NPs for both
      species. A 48-h exposure to 1 mg.L-1 induced a decrease of 30% and 40% of the SV
      in D. pulex and D. similis, respectively. However at higher concentrations, the
      SV of D. similis was more impacted (60% off for 10 mg.L-1 and 100 mg.L-1) than
      the one of D. pulex. These interspecific toxic effects of CeO2 NPs are explained
      by morphological variations such as the presence of reliefs on the cuticle and a
      longer distal spine in D. similis acting as traps for the CeO2 aggregates. In
      addition, D. similis has a mean SV double that of D. pulex and thus initially
      collides with twice more NPs aggregates. The ecotoxicological consequences on the
      behavior and physiology of a CeO2 NPs exposure in daphnids are discussed.

PMID- 23977005
TI  - Cell surface glycan alterations in epithelial mesenchymal transition process of
      Huh7 hepatocellular carcinoma cell.
AB  - BACKGROUND AND OBJECTIVE: Due to recurrence and metastasis, the mortality of
      Hepatocellular carcinoma (HCC) is high. It is well known that the epithelial
      mesenchymal transition (EMT) and glycan of cell surface glycoproteins play
      pivotal roles in tumor metastasis. The goal of this study was to identify HCC
      metastasis related differential glycan pattern and their enzymatic basis using a
      HGF induced EMT model. METHODOLOGY: HGF was used to induce HCC EMT model. Lectin
      microarray was used to detect the expression of cell surface glycan and the
      difference was validated by lectin blot and fluorescence cell lectin
      immunochemistry. The mRNA expression levels of glycotransferases were determined
      by qRT-PCR. RESULTS: After HGF treatment, the Huh7 cell lost epithelial
      characteristics and obtained mesenchymal markers. These changes demonstrated that
      HGF could induce a typical cell model of EMT. Lectin microarray analysis
      identified a decreased affinity in seven lectins ACL, BPL, JAC, MPL, PHA-E, SNA,
      and SBA to the glycan of cell surface glycoproteins. This implied that glycan
      containing T/Tn-antigen, NA2 and bisecting GlcNAc, Siaalpha2-6Gal/GalNAc,
      terminal alpha or betaGalNAc structures were reduced. The binding ability of
      thirteen lectins, AAL, LCA, LTL, ConA, NML, NPL, DBA, HAL, PTL II, WFL, ECL, GSL
      II and PHA-L to glycan were elevated, and a definite indication that glycan
      containing terminal alphaFuc and +/- Sia-Le, core fucose, alpha-man, gal
      beta(alpha) GalNAc, beta1,6 GlcNAc branching and tetraantennary complex
      oligosaccharides structures were increased. These results were further validated
      by lectin blot and fluorescence cell lectin-immunochemistry. Furthermore, the
      mRNA expression level of Mgat3 decreased while that of Mgat5, FucT8 and
      beta3GalT5 increased. Therefore, cell surface glycan alterations in the EMT
      process may coincide with the expression of glycosyltransferase. CONCLUSIONS: The
      findings of this study systematically clarify the alterations of cell surface
      glycan in cancer EMT, and may provide novel insight for HCC metastasis.

PMID- 23977006
TI  - A catalyzing phantom for reproducible dynamic conversion of hyperpolarized [1
      13C]-pyruvate.
AB  - In vivo real time spectroscopic imaging of hyperpolarized 13C labeled metabolites
      shows substantial promise for the assessment of physiological processes that were
      previously inaccessible. However, reliable and reproducible methods of
      measurement are necessary to maximize the effectiveness of imaging biomarkers
      that may one day guide personalized care for diseases such as cancer. Animal
      models of human disease serve as poor reference standards due to the complexity,
      heterogeneity, and transient nature of advancing disease. In this study, we
      describe the reproducible conversion of hyperpolarized [1-13C]-pyruvate to [1
      13C]-lactate using a novel synthetic enzyme phantom system. The rate of reaction
      can be controlled and tuned to mimic normal or pathologic conditions of varying
      degree. Variations observed in the use of this phantom compare favorably against
      within-group variations observed in recent animal studies. This novel phantom
      system provides crucial capabilities as a reference standard for the
      optimization, comparison, and certification of quantitative imaging strategies
      for hyperpolarized tracers.

PMID- 23977007
TI  - Genome-wide relatedness of Treponema pedis, from gingiva and necrotic skin
      lesions of pigs, with the human oral pathogen Treponema denticola.
AB  - Treponema pedis and T. denticola are two genetically related species with
      different origins of isolation. Treponema denticola is part of the human oral
      microbiota and is associated with periodontitis while T. pedis has been isolated
      from skin lesions in animals, e.g., digital dermatitis in cattle and necrotic
      ulcers in pigs. Although multiple Treponema phylotypes may exist in ulcerative
      lesions in pigs, T. pedis appears to be a predominant spirochete in these
      lesions. Treponema pedis can also be present in pig gingiva. In this study, we
      determined the complete genome sequence of T. pedis strain T A4, isolated from a
      porcine necrotic ear lesion, and compared its genome with that of T. denticola.
      Most genes in T. pedis were homologous to those in T. denticola and the two
      species were similar in general genomic features such as size, G+C content, and
      number of genes. In addition, many homologues of specific virulence-related genes
      in T. denticola were found in T. pedis. Comparing a selected pair of strains will
      usually not give a complete picture of the relatedness between two species. We
      therefore complemented the analysis with draft genomes from six T. pedis
      isolates, originating from gingiva and necrotic ulcers in pigs, and from twelve
      T. denticola strains. Each strain carried a considerable amount of accessory
      genetic material, of which a large part was strain specific. There was also
      extensive sequence variability in putative virulence-related genes between
      strains belonging to the same species. Signs of lateral gene-transfer events from
      bacteria known to colonize oral environments were found. This suggests that the
      oral cavity is an important habitat for T. pedis. In summary, we found extensive
      genomic similarities between T. pedis and T. denticola but also large variability
      within each species. 

PMID- 23977008
TI  - Down-regulation of the oncogene PTTG1 via the KLF6 tumor suppressor during
      induction of myeloid differentiation.
AB  - The aberrant expression of proto-oncogenes is involved in processes that are
      responsible for cellular proliferation and the inhibition of myeloid
      differentiation in acute myeloid leukemia (AML). Pituitary Tumor-Transforming
      gene 1 (PTTG1), an oncogenic transcription factor, is abundantly expressed in
      various human cancers and hematopoietic malignancies. However, its expression in
      normal leukocytes and most normal tissues is very low or undetectable. The
      mechanism by which PTTG1 overexpression modifies myeloid cell development and
      promotes leukemogenesis remain unclear. To investigate the mechanistic links
      between PTTG1 overexpression and leukemia cell differentiation, we utilized
      phorbol 12-myristate 13-acetate (PMA), a well-known agent that triggers
      monocyte/macrophage differentiation, to analyze the expression patterns of PTTG1
      in PMA-induced myeloid differentiation. We found that PTTG1 is down-regulated at
      the transcriptional level in PMA-treated HL-60 and THP1 cells. In addition, we
      identified a binding site for a tumor suppressor protein, Kruppel-like factor 6
      (KLF6), in the PTTG1 promoter. We found that KLF6 could directly bind and repress
      PTTG1 expression. In HL-60 and THP1 cells, KLF6 mRNA and protein levels are up
      regulated with a concordant reduction of PTTG1 expression upon treatment with
      PMA. Furthermore, KLF6 knockdown by shRNA abolished the suppression of PTTG1 and
      reduced the activation of the differentiation marker CD11b in PMA-primed cells.
      The protein kinase C (PKC) inhibitor and the MAPK/ERK kinase (MEK) inhibitor
      significantly blocked the potentiation of PMA-mediated KLF6 induction and the
      down-regulation of PTTG1, indicating that PTTG1 is suppressed via the activation
      of PKC/ERK/KLF6 pathway. Our findings suggest that drugs that increase the KLF6
      inhibition of PTTG1 may have a therapeutic application in AML treatment
      strategies. 

PMID- 23977010
TI  - Early affective processing in patients with acute posttraumatic stress disorder:
      magnetoencephalographic correlates.
AB  - BACKGROUND: In chronic PTSD, a preattentive neural alarm system responds rapidly
      to emotional information, leading to increased prefrontal cortex (PFC) activation
      at early processing stages (<100 ms). Enhanced PFC responses are followed by a
      reduction in occipito-temporal activity during later processing stages. However,
      it remains unknown if this neuronal pattern is a result of a long lasting mental
      disorder or if it represents changes in brain function as direct consequences of
      severe trauma. METHODOLOGY: The present study investigates early fear network
      activity in acutely traumatized patients with PTSD. It focuses on the question
      whether dysfunctions previously observed in chronic PTSD patients are already
      present shortly after trauma exposure. We recorded neuromagnetic activity towards
      emotional pictures in seven acutely traumatized PTSD patients between one and
      seven weeks after trauma exposure and compared brain responses to a balanced
      healthy control sample. Inverse modelling served for mapping sources of
      differential activation in the brain. PRINCIPAL FINDINGS: Compared to the control
      group, acutely traumatized PTSD patients showed an enhanced PFC response to high
      arousing pictures between 60 to 80 ms. This rapid prefrontal hypervigilance
      towards arousing pictorial stimuli was sustained during 120-300 ms, where it was
      accompanied by a reduced affective modulation of occipito-temporal neural
      processing. CONCLUSIONS: Our findings indicate that the hypervigilance-avoidance
      pattern seen in chronic PTSD is not necessarily a product of an endured mental
      disorder, but arises as an almost immediate result of severe traumatisation.
      Thus, traumatic experiences can influence emotion processing strongly, leading to
      long-lasting changes in trauma network activation and expediting a chronic
      manifestation of maladaptive cognitive and behavioral symptoms.

PMID- 23977009
TI  - Ghrelin receptor (GHS-R1A) antagonism suppresses both alcohol consumption and the
      alcohol deprivation effect in rats following long-term voluntary alcohol
      consumption.
AB  - Alcohol dependence is a heterogeneous disorder where several signalling systems
      play important roles. Recent studies implicate that the gut-brain hormone
      ghrelin, an orexigenic peptide, is a potential mediator of alcohol related
      behaviours. Ghrelin increases whereas a ghrelin receptor (GHS-R1A) antagonist
      decreases alcohol consumption as well as operant self-administration of alcohol
      in rodents that have consumed alcohol for twelve weeks. In the present study we
      aimed at investigating the effect of acute and repeated treatment with the GHS
      R1A antagonist JMV2959 on alcohol intake in a group of rats following voluntarily
      alcohol consumption for two, five and eight months. After approximately ten
      months of voluntary alcohol consumption the expression of the GHS-R1A gene (Ghsr)
      as well as the degree of methylation of a CpG island found in Ghsr was examined
      in reward related brain areas. In a separate group of rats, we examined the
      effect of the JMV2959 on alcohol relapse using the alcohol deprivation paradigm.
      Acute JMV2959 treatment was found to decrease alcohol intake and the effect was
      more pronounced after five, compared to two months of alcohol exposure. In
      addition, repeated JMV2959 treatment decreased alcohol intake without inducing
      tolerance or rebound increase in alcohol intake after the treatment. The GHS-R1A
      antagonist prevented the alcohol deprivation effect in rats. There was a
      significant down-regulation of the Ghsr expression in the ventral tegmental area
      (VTA) in high- compared to low-alcohol consuming rats after approximately ten
      months of voluntary alcohol consumption. Further analysis revealed a negative
      correlation between Ghsr expression in the VTA and alcohol intake. No differences
      in methylation degree were found between high- compared to low-alcohol consuming
      rats. These findings support previous studies showing that the ghrelin signalling
      system may constitute a potential target for development of novel treatment
      strategies for alcohol dependence. 

PMID- 23977011
TI  - Climate change impacts on streamflow and subbasin-scale hydrology in the Upper
      Colorado River Basin.
AB  - In the Upper Colorado River Basin (UCRB), the principal source of water in the
      southwestern U.S., demand exceeds supply in most years, and will likely continue
      to rise. While General Circulation Models (GCMs) project surface temperature
      warming by 3.5 to 5.6 degrees C for the area, precipitation projections are
      variable, with no wetter or drier consensus. We assess the impacts of projected
      21(st) century climatic changes on subbasins in the UCRB using the Soil and Water
      Assessment Tool, for all hydrologic components (snowmelt, evapotranspiration,
      surface runoff, subsurface runoff, and streamflow), and for 16 GCMs under the A2
      emission scenario. Over the GCM ensemble, our simulations project median Spring
      streamflow declines of 36% by the end of the 21(st) century, with increases more
      likely at higher elevations, and an overall range of -100 to +68%. Additionally,
      our results indicated Summer streamflow declines with median decreases of 46%,
      and an overall range of -100 to +22%. Analysis of hydrologic components indicates
      large spatial and temporal changes throughout the UCRB, with large snowmelt
      declines and temporal shifts in most hydrologic components. Warmer temperatures
      increase average annual evapotranspiration by ~23%, with shifting seasonal soil
      moisture availability driving these increases in late Winter and early Spring.
      For the high-elevation water-generating regions, modest precipitation decreases
      result in an even greater water yield decrease with less available snowmelt.
      Precipitation increases with modest warming do not translate into the same
      magnitude of water-yield increases due to slight decreases in snowmelt and
      increases in evapotranspiration. For these basins, whether modest warming is
      associated with precipitation decreases or increases, continued rising
      temperatures may make drier futures. Subsequently, many subbasins are projected
      to turn from semi-arid to arid conditions by the 2080 s. In conclusion, water
      availability in the UCRB could significantly decline with adverse consequences
      for water supplies, agriculture, and ecosystem health. 

PMID- 23977012
TI  - Regulatory phosphorylation of Ikaros by Bruton's tyrosine kinase.
AB  - Diminished Ikaros function has been implicated in the pathogenesis of acute
      lymphoblastic leukemia (ALL), the most common form of childhood cancer.
      Therefore, a stringent regulation of Ikaros is of paramount importance for normal
      lymphocyte ontogeny. Here we provide genetic and biochemical evidence for a
      previously unknown function of Bruton's tyrosine kinase (BTK) as a partner and
      posttranslational regulator of Ikaros, a zinc finger-containing DNA-binding
      protein that plays a pivotal role in immune homeostasis. We demonstrate that BTK
      phosphorylates Ikaros at unique phosphorylation sites S214 and S215 in the close
      vicinity of its zinc finger 4 (ZF4) within the DNA binding domain, thereby
      augmenting its nuclear localization and sequence-specific DNA binding activity.
      Our results further demonstrate that BTK-induced activating phosphorylation is
      critical for the optimal transcription factor function of Ikaros. 

PMID- 23977013
TI  - Involvement of renal corpuscle microRNA expression on epithelial-to-mesenchymal
      transition in maternal low protein diet in adult programmed rats.
AB  - Prior study shows that maternal protein-restricted (LP) 16-wk-old offspring have
      pronounced reduction of nephron number and arterial hypertension associated with
      unchanged glomerular filtration rate, besides enhanced glomerular area, which may
      be related to glomerular hyperfiltration/overflow and which accounts for the
      glomerular filtration barrier breakdown and early glomerulosclerosis. In the
      current study, LP rats showed heavy proteinuria associated with podocyte
      simplification and foot process effacement. TGF-beta1 glomerular expression was
      significantly enhanced in LP. Isolated LP glomeruli show a reduced level of miR
      200a, miR-141, miR-429 and ZEB2 mRNA and upregulated collagen 1alpha1/2 mRNA
      expression. By western blot analyzes of whole kidney tissue, we found significant
      reduction of both podocin and nephrin and enhanced expression of mesenchymal
      protein markers such as desmin, collagen type I and fibronectin. From our present
      knowledge, these are the first data showing renal miRNA modulation in the protein
      restriction model of fetal programming. The fetal-programmed adult offspring
      showed pronounced structural glomerular disorders with an accentuated and
      advanced stage of fibrosis, which led us to state that the glomerular miR-200
      family would be downregulated by TGF-beta1 action inducing ZEB 2 expression that
      may subsequently cause glomeruli epithelial-to-mesenchymal transition. 

PMID- 23977014
TI  - Population cancer risks associated with coal mining: a systematic review.
AB  - BACKGROUND: Coal is produced across 25 states and provides 42% of US energy. With
      production expected to increase 7.6% by 2035, proximate populations remain at
      risk of exposure to carcinogenic coal products such as silica dust and organic
      compounds. It is unclear if population exposure is associated with increased
      risk, or even which cancers have been studied in this regard. METHODS: We
      performed a systematic review of English-language manuscripts published since
      1980 to determine if coal mining exposure was associated with increased cancer
      risk (incidence and mortality). RESULTS: Of 34 studies identified, 27 studied
      coal mining as an occupational exposure (coal miner cohort or as a retrospective
      risk factor) but only seven explored health effects in surrounding populations.
      Overall, risk assessments were reported for 20 cancer site categories, but their
      results and frequency varied considerably. Incidence and mortality risk
      assessments were: negative (no increase) for 12 sites; positive for 1 site; and
      discordant for 7 sites (e.g. lung, gastric). However, 10 sites had only a single
      study reporting incidence risk (4 sites had none), and 11 sites had only a single
      study reporting mortality risk (2 sites had none). The ecological study data were
      particularly meager, reporting assessments for only 9 sites. While mortality
      assessments were reported for each, 6 had only a single report and only 2 sites
      had reported incidence assessments. CONCLUSIONS: The reported assessments are too
      meager, and at times contradictory, to make definitive conclusions about
      population cancer risk due to coal mining. However, the preponderance of this and
      other data support many of Hill's criteria for causation. The paucity of data
      regarding population exposure and risk, the widespread geographical extent of
      coal mining activity, and the continuing importance of coal for US energy,
      warrant further studies of population exposure and risk.

PMID- 23977015
TI  - Rural/urban background, depression and suicidal ideation in Chinese college
      students: a cross-sectional study.
AB  - OBJECTIVES: The objective of this study was to examine, first, the relationship
      of having a rural vs. urban background with suicidal ideation in Chinese college
      students, and second, whether a potential relationship was mediated by
      depression. METHODS: A survey was conducted among 1,145 undergraduate students at
      a university in China. Suicidal ideation and depressive symptoms were measured by
      the revised Hopkins' Symptom checklist (SCL-90-R). Associations between rural vs.
      urban background, depression and suicidal ideation were estimated by
      multivariable linear regression-based beta coefficients, logistic regression
      based odds ratios (ORs), and corresponding 95% confidence intervals (CIs). The
      magnitude of indirect effect and bias-corrected 95% CIs were obtained through
      bootstrap techniques. RESULTS: Rural background was positively associated with
      depression, which was in turn associated with suicidal ideation. The OR for rural
      status and suicidal ideation equaled 2.15 (95% CI = 1.36-3.41). This OR was
      slightly, though significantly (p<0.05) attenuated by additional adjustment for
      depressive symptoms (OR = 1.99, 95% CI = 1.15-3.44). CONCLUSION: Having a rural
      background is a determinant of suicidal ideation in Chinese college students.
      Depression may only marginally mediate this association.

PMID- 23977016
TI  - A smartphone ecological momentary assessment/intervention "app" for collecting
      real-time data and promoting self-awareness.
AB  - We have designed a flexible ecological momentary assessment/intervention
      smartphone (EMA/EMI) "app". We examine the utility of this app for collecting
      real-time data, and assessing intra-subject variability, by using it to assess
      how freshman undergraduates spend their time. We also explore whether its use can
      promote greater self-awareness. Participants were randomly divided into an
      experimental group, who used the app, and a control group, who did not. We used
      the app to collect both randomized in-the-moment data as well as end-of-day data
      to assess time use. Using a posttest survey we asked participants questions about
      how they spent time throughout the school semester. We also asked the
      experimental group about their experience with the app. Among other findings,
      80.49% participants indicated that they became more aware of how they spent their
      time using the app. Corroborating this report, among the experimental group, end
      of-semester self-assessment of time spent wasted, and time spent using
      electronics recreationally, predicted semester GPA at a strength comparable to
      high school GPA and ACT score (two of the best single predictors for first
      semester college GPA), but had no correlation among controls. We discuss the
      advantages and limitations of using apps, such as ours, for EMA and/or EMI. 

PMID- 23977018
TI  - Ongoing speciation in the Tibetan plateau Gymnocypris species complex.
AB  - Local adaptation towards divergent ecological conditions often results in genetic
      differentiation and adaptive phenotypic divergence. To illuminate the ecological
      distinctiveness of the schizothoracine fish, we studied a Gymnocypris species
      complex consisting of three morphs distributed across four bodies of water (the
      Yellow River, Lake Qinghai, the Ganzi River and Lake Keluke) in the Northeast
      Tibetan Plateau. We used a combination of mitochondrial (16S rRNA and Cyt b) and
      nuclear (RAG-2) genetic sequences to investigate the phylogeography of these
      morphs based on a sample of 277 specimens. Analysis of gill rakers allowed for
      mapping of phenotypic trajectories along the phylogeny. The phylogenetic and
      morphological analyses showed that the three sparsely rakered morphs were present
      at two extremes of the phylogenetic tree: the Yellow River morphs were located at
      the basal phylogenetic split, and the Lake Keluke and Ganzi River morphs at the
      peak, with the densely rakered Lake Qinghai morphs located between these two
      extremes. Age estimation further indicated that the sparsely rakered morphs
      constituted the oldest and youngest lineages, whereas the densely rakered morph
      was assigned to an intermediate-age lineage. These results are most compatible
      with the process of evolutionary convergence or reversal. Disruptive natural
      selection due to divergent habitats and dietary preferences is likely the driving
      force behind the formation of new morphs, and the similarities between their
      phenotypes may be attributable to the similarities between their forms of niche
      tracking associated with food acquisition. This study provides the first genetic
      evidence for the occurrence of convergence or reversal in the schizothoracine
      fish of the Tibetan Plateau at small temporal scales. 

PMID- 23977017
TI  - Whole genome duplication and enrichment of metal cation transporters revealed by
      de novo genome sequencing of extremely halotolerant black yeast Hortaea
      werneckii.
AB  - Hortaea werneckii, ascomycetous yeast from the order Capnodiales, shows an
      exceptional adaptability to osmotically stressful conditions. To investigate this
      unusual phenotype we obtained a draft genomic sequence of a H. werneckii strain
      isolated from hypersaline water of solar saltern. Two of its most striking
      characteristics that may be associated with a halotolerant lifestyle are the
      large genetic redundancy and the expansion of genes encoding metal cation
      transporters. Although no sexual state of H. werneckii has yet been described, a
      mating locus with characteristics of heterothallic fungi was found. The total
      assembly size of the genome is 51.6 Mb, larger than most phylogenetically related
      fungi, coding for almost twice the usual number of predicted genes (23333). The
      genome appears to have experienced a relatively recent whole genome duplication,
      and contains two highly identical gene copies of almost every protein. This is
      consistent with some previous studies that reported increases in genomic DNA
      content triggered by exposure to salt stress. In hypersaline conditions
      transmembrane ion transport is of utmost importance. The analysis of predicted
      metal cation transporters showed that most types of transporters experienced
      several gene duplications at various points during their evolution. Consequently
      they are present in much higher numbers than expected. The resulting diversity of
      transporters presents interesting biotechnological opportunities for improvement
      of halotolerance of salt-sensitive species. The involvement of plasma P-type H+
      ATPases in adaptation to different concentrations of salt was indicated by their
      salt dependent transcription. This was not the case with vacuolar H+ ATPases,
      which were transcribed constitutively. The availability of this genomic sequence
      is expected to promote the research of H. werneckii. Studying its extreme
      halotolerance will not only contribute to our understanding of life in
      hypersaline environments, but should also identify targets for improving the salt
      and osmotolerance of economically important plants and microorganisms.

PMID- 23977019
TI  - Plasmacytoid dendritic cells are crucial in Bifidobacterium adolescentis-mediated
      inhibition of Yersinia enterocolitica infection.
AB  - In industrialized countries bacterial intestinal infections are commonly caused
      by enteropathogenic Enterobacteriaceae. The interaction of the microbiota with
      the host immune system determines the adequacy of an appropriate response against
      pathogens. In this study we addressed whether the probiotic Bifidobacterium
      adolescentis is protective during intestinal Yersinia enterocolitica infection.
      Female C57BL/6 mice were fed with B. adolescentis, infected with Yersinia
      enterocolitica, or B. adolescentis fed and subsequently infected with Yersinia
      enterocolitica. B. adolescentis fed and Yersinia infected mice were protected
      from Yersinia infection as indicated by a significantly reduced weight loss and
      splenic Yersinia load when compared to Yersinia infected mice. Moreover,
      protection from infection was associated with increased intestinal plasmacytoid
      dendritic cell and regulatory T-cell frequencies. Plasmacytoid dendritic cell
      function was investigated using depletion experiments by injecting B.
      adolescentis fed, Yersinia infected C57BL/6 mice with anti-mouse PDCA-1 antibody,
      to deplete plasmacytoid dendritic cells, or respective isotype control. The B.
      adolescentis-mediated protection from Yersinia dissemination to the spleen was
      abrogated after plasmacytoid dendritic cell depletion indicating a crucial
      function for pDC in control of intestinal Yersinia infection. We suggest that
      feeding of B. adolescentis modulates the intestinal immune system in terms of
      increased plasmacytoid dendritic cell and regulatory T-cell frequencies, which
      might account for the B. adolescentis-mediated protection from Yersinia
      enterocolitica infection. 

PMID- 23977020
TI  - Cognitive dysfunction precedes the onset of motor symptoms in the MitoPark mouse
      model of Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder primarily characterized
      by progressive loss of dopamine neurons, leading to loss of motor coordination.
      However, PD is associated with a high rate of non-motor neuropsychiatric
      comorbities that often develop before the onset of movement symptoms. The
      MitoPark transgenic mouse model is the first to recapitulate the cardinal
      clinical features, namely progressive neurodegeneration and death of neurons,
      loss of motor function and therapeutic response to L-DOPA. To investigate whether
      MitoPark mice exhibit early onset of cognitive impairment, a non-motor
      neuropsychiatric comorbidity, we measured performance on a spatial learning and
      memory task before (~8 weeks) or after (~20 weeks) the onset of locomotor decline
      in MitoPark mice or in littermate controls. Consistent with previous studies, we
      established that a progressive loss of spontaneous locomotor activity began at 12
      weeks of age, which was followed by progressive loss of body weight beginning at
      16-20 weeks. Spatial learning and memory was measured using the Barnes Maze. By
      20 weeks of age, MitoPark mice displayed a substantial reduction in overall
      locomotor activity that impaired their ability to perform the task. However, in
      the 8-week-old mice, locomotor activity was no different between genotypes, yet
      MitoPark mice took longer, traveled further and committed more errors than same
      age control mice, while learning to successfully navigate the maze. The modest
      between-day learning deficit of MitoPark mice was characterized by impaired
      within-day learning during the first two days of testing. No difference was
      observed between genotypes during probe trials conducted one or twelve days after
      the final acquisition test. Additionally, 8-week-old MitoPark mice exhibited
      impaired novel object recognition when compared to control mice. Together, these
      data establish that mild cognitive impairment precedes the loss of motor function
      in a novel rodent model of PD, which may provide unique opportunities for
      therapeutic development. 

PMID- 23977021
TI  - Investigation of cigarette smoking among male schizophrenia patients.
AB  - Male schizophrenia patients are known to have a heavier smoking pattern compared
      with the general population. However, the mechanism for this association is not
      known, though hypothesis that smoking could alleviate symptomatology of
      schizophrenia and reduce side effects of antipsychotics has been suggested. The
      aims of this study were to validate the heavier smoking pattern among male
      schizophrenia patients and to investigate the possible mechanisms for the
      association. To enhance the reliability of the study, we recruited two large
      independent samples with 604 and 535 male Chinese schizophrenia patients, and
      compared their smoking pattern with that of 535 healthy male controls recruited
      from general population. Validated multiple indicators and multiple causes
      structure equation model and regression models were used to investigate the
      association of smoking with factors of schizophrenia symptomatology and with the
      usage of antipsychotics and their extra-pyramidal side effects (EPS).
      Schizophrenia patients had significantly heavier smoking pattern compared with
      healthy controls in our sample (42.4% vs. 16.8%, p<0.001 for current smoking
      prevalence; 23.5% vs. 43.3%, p<0.001 for smoking cessation rate; 24.5% vs. 3.0%,
      p<0.001 for heavy smoker proportion). Their smoking status was also found to be
      consistently and significantly associated with reduced negative factor scores for
      schizophrenia symptomatology (beta = -0.123, p = 0.051 for sample-A; beta = 
      0.103, p = 0.035 for sample-B; beta = -0.082, p = 0.017 for the combined sample).
      However, no significant association was found between smoking and antipsychotics
      usage or risk of EPS. These results support that smoking is associated with
      improved negative symptoms, which could account for the heavier smoking pattern
      among schizophrenia patients. 

PMID- 23977023
TI  - Icaritin synergistically enhances the radiosensitivity of 4T1 breast cancer
      cells.
AB  - Icaritin (ICT) is a hydrolytic form of icariin isolated from plants of the genus
      Epimedium. This study was to investigate the radiosensitization effect of
      icaritin and its possible underlying mechanism using murine 4T1 breast cancer
      cells. The combination of Icaritin at 3 uM or 6 uM with 6 or 8 Gy of ionizing
      radiation (IR) in the clonogenic assay yielded an ER (enhancement ratio) of 1.18
      or 1.28, CI (combination index) of 0.38 or 0.19 and DRI (dose reducing index) of
      2.51 or 5.07, respectively. These strongly suggest that Icaritin exerted a
      synergistic killing (?) effect with radiation on the tumor cells. This effect
      might relate with bioactivities of ICT: 1) exert an anti-proliferative effect in
      a dose- and time-dependent manner, which is different from IR killing effect but
      likely work together with the IR effect; 2) suppress the IR-induced activation of
      two survival paths, ERK1/2 and AKT; 3) induce the G2/M blockage, enhancing IR
      killing effect; and 4) synergize with IR to enhance cell apoptosis. In addition,
      ICT suppressed angiogenesis in chick embryo chorioallantoic membrane (CAM) assay.
      Taken together, ICT is a new radiosensitizer and can enhance anti-cancer effect
      of IR or other therapies. 

PMID- 23977022
TI  - Population genomics of cardiometabolic traits: design of the University College
      London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB)
      Consortium.
AB  - Substantial advances have been made in identifying common genetic variants
      influencing cardiometabolic traits and disease outcomes through genome wide
      association studies. Nevertheless, gaps in knowledge remain and new questions
      have arisen regarding the population relevance, mechanisms, and applications for
      healthcare. Using a new high-resolution custom single nucleotide polymorphism
      (SNP) array (Metabochip) incorporating dense coverage of genomic regions linked
      to cardiometabolic disease, the University College-London School-Edinburgh
      Bristol (UCLEB) consortium of highly-phenotyped population-based prospective
      studies, aims to: (1) fine map functionally relevant SNPs; (2) precisely estimate
      individual absolute and population attributable risks based on individual SNPs
      and their combination; (3) investigate mechanisms leading to altered risk factor
      profiles and CVD events; and (4) use Mendelian randomisation to undertake studies
      of the causal role in CVD of a range of cardiovascular biomarkers to inform
      public health policy and help develop new preventative therapies. 

PMID- 23977024
TI  - TBCK influences cell proliferation, cell size and mTOR signaling pathway.
AB  - Mammalian target of rapamycin (mTOR) is a central regulator for both cell
      proliferation and cell growth; however, little is known about the regulation of
      mTOR expression at the transcriptional level. Here, we provide evidences that a
      conserved human protein TBCK (TBC1 domain containing kinase) is involved in the
      regulation of mTOR signaling pathway. Depletion of TBCK significantly inhibits
      cell proliferation, reduces cell size, and disrupts the organization of actin,
      but not microtubule. Knockdown of TBCK induces a significant decrease in the
      protein levels of components of mTOR complex (mTORC), and suppresses the activity
      of mTOR signaling, but not MAPK or PDK1/Akt pathway. Further results show that
      TBCK influences the expression of mTORC components at the transcriptional level.
      Thus, these data suggest that TBCK may play an important role in cell
      proliferation, cell growth and actin organization possibly by modulating mTOR
      pathway. 

PMID- 23977025
TI  - Acute mechanical stretch promotes eNOS activation in venous endothelial cells
      mainly via PKA and Akt pathways.
AB  - In the vasculature, physiological levels of nitric oxide (NO) protect against
      various stressors, including mechanical stretch. While endothelial NO production
      in response to various stimuli has been studied extensively, the precise
      mechanism underlying stretch-induced NO production in venous endothelial cells
      remains incompletely understood. Using a model of continuous cellular stretch, we
      found that stretch promoted phosphorylation of endothelial NO synthase (eNOS) at
      Ser1177, Ser633 and Ser615 and NO production in human umbilical vein endothelial
      cells. Although stretch activated the kinases AMPKalpha, PKA, Akt, and ERK1/2,
      stretch-induced eNOS activation was only inhibited by kinase-specific inhibitors
      of PKA and PI3K/Akt, but not of AMPKalpha and Erk1/2. Similar results were
      obtained with knockdown by shRNAs targeting the PKA and Akt genes. Furthermore,
      inhibition of PKA preferentially attenuated eNOS activation in the early phase,
      while inhibition of the PI3K/Akt pathway reduced eNOS activation in the late
      phase, suggesting that the PKA and PI3K/Akt pathways play distinct roles in a
      time-dependent manner. Finally, we investigated the role of these pathways in
      stretch-induced endothelial exocytosis and leukocyte adhesion. Interestingly, we
      found that inhibition of the PI3K/Akt pathway increased stretch-induced Weibel
      Palade body exocytosis and leukocyte adhesion, while inhibition of the PKA
      pathway had the opposite effects, suggesting that the exocytosis-promoting effect
      of PKA overwhelms the inhibitory effect of PKA-mediated NO production. Taken
      together, the results suggest that PKA and Akt are important regulators of eNOS
      activation in venous endothelial cells under mechanical stretch, while playing
      different roles in the regulation of stretch-induced endothelial exocytosis and
      leukocyte adhesion.

PMID- 23977026
TI  - The effect of primer choice and short read sequences on the outcome of 16S rRNA
      gene based diversity studies.
AB  - Different regions of the bacterial 16S rRNA gene evolve at different evolutionary
      rates. The scientific outcome of short read sequencing studies therefore alters
      with the gene region sequenced. We wanted to gain insight in the impact of primer
      choice on the outcome of short read sequencing efforts. All the unknowns
      associated with sequencing data, i.e. primer coverage rate, phylogeny, OTU
      richness and taxonomic assignment, were therefore implemented in one study for
      ten well established universal primers (338f/r, 518f/r, 799f/r, 926f/r and
      1062f/r) targeting dispersed regions of the bacterial 16S rRNA gene. All analyses
      were performed on nearly full length and in silico generated short read sequence
      libraries containing 1175 sequences that were carefully chosen as to present a
      representative substitute of the SILVA SSU database. The 518f and 799r primers,
      targeting the V4 region of the 16S rRNA gene, were found to be particularly
      suited for short read sequencing studies, while the primer 1062r, targeting V6,
      seemed to be least reliable. Our results will assist scientists in considering
      whether the best option for their study is to select the most informative primer,
      or the primer that excludes interferences by host-organelle DNA. The methodology
      followed can be extrapolated to other primers, allowing their evaluation prior to
      the experiment. 

PMID- 23977027
TI  - Disruption in connexin-based communication is associated with intracellular Ca2+
      signal alterations in astrocytes from Niemann-Pick type C mice.
AB  - Reduced astrocytic gap junctional communication and enhanced hemichannel activity
      were recently shown to increase astroglial and neuronal vulnerability to
      neuroinflammation. Moreover, increasing evidence suggests that neuroinflammation
      plays a pivotal role in the development of Niemann-Pick type C (NPC) disease, an
      autosomal lethal neurodegenerative disorder that is mainly caused by mutations in
      the NPC1 gene. Therefore, we investigated whether the lack of NPC1 expression in
      murine astrocytes affects the functional state of gap junction channels and
      hemichannels. Cultured cortical astrocytes of NPC1 knock-out mice (Npc1-/-)
      showed reduced intercellular communication via gap junctions and increased
      hemichannel activity. Similarly, astrocytes of newborn Npc1-/- hippocampal slices
      presented high hemichannel activity, which was completely abrogated by connexin
      43 hemichannel blockers and was resistant to inhibitors of pannexin 1
      hemichannels. Npc1-/- astrocytes also showed more intracellular Ca2+ signal
      oscillations mediated by functional connexin 43 hemichannels and P2Y1 receptors.
      Therefore, Npc1-/- astrocytes present features of connexin based channels
      compatible with those of reactive astrocytes and hemichannels might be a novel
      therapeutic target to reduce neuroinflammation in NPC disease.

PMID- 23977028
TI  - Prognostic value of histological response to chemotherapy in osteosarcoma
      patients receiving tumor-bearing frozen autograft.
AB  - BACKGROUND: A variety of surgical procedures are now available for tissue
      reconstruction after osteosarcoma excision, and an important prognostic factor is
      the evaluation of response to chemotherapy using histology. Although tumor
      bearing autografts are useful tools for reconstruction, re-use of the primary
      tumor may make it difficult to assess the histological response to chemotherapy,
      since the entire tumor cannot be analyzed. Here, we analyzed the prognostic value
      of the histological response in the patients who received frozen tumor-bearing
      autografts for reconstruction. METHOD: Retrospective analysis of the medical
      records of 51 patients with high-grade osteosarcoma of the extremities was
      performed. All patients received reconstruction using frozen tumor-bearing
      autografts. Tumor necrosis was evaluated in extraskeletal masses and cancellous
      bone. RESULTS: Five-year overall survival of patients with good and poor response
      to chemotherapy was 82.9% and 46.4%, respectively (P = 0.044), and 5-year event
      free survival was 57.7% and 36.0%, respectively (P = 0.329). Multivariate
      analysis revealed that a poor histological response to chemotherapy was a
      significant prognostic factor for overall survival (P = 0.033). CONCLUSION:
      Histological response is an important and reliable prognostic factor in patients
      undergoing reconstruction using frozen tumor-bearing autografts.

PMID- 23977029
TI  - Rapid cohort generation and analysis of disease spectrum of large animal model of
      cone dystrophy.
AB  - Large animal models are an important resource for the understanding of human
      disease and for evaluating the applicability of new therapies to human patients.
      For many diseases, such as cone dystrophy, research effort is hampered by the
      lack of such models. Lentiviral transgenesis is a methodology broadly applicable
      to animals from many different species. When conjugated to the expression of a
      dominant mutant protein, this technology offers an attractive approach to
      generate new large animal models in a heterogeneous background. We adopted this
      strategy to mimic the phenotype diversity encounter in humans and generate a
      cohort of pigs for cone dystrophy by expressing a dominant mutant allele of the
      guanylate cyclase 2D (GUCY2D) gene. Sixty percent of the piglets were transgenic,
      with mutant GUCY2D mRNA detected in the retina of all animals tested. Functional
      impairment of vision was observed among the transgenic pigs at 3 months of age,
      with a follow-up at 1 year indicating a subsequent slower progression of
      phenotype. Abnormal retina morphology, notably among the cone photoreceptor cell
      population, was observed exclusively amongst the transgenic animals. Of
      particular note, these transgenic animals were characterized by a range in the
      severity of the phenotype, reflecting the human clinical situation. We
      demonstrate that a transgenic approach using lentiviral vectors offers a powerful
      tool for large animal model development. Not only is the efficiency of
      transgenesis higher than conventional transgenic methodology but this technique
      also produces a heterogeneous cohort of transgenic animals that mimics the
      genetic variation encountered in human patients. 

PMID- 23977030
TI  - Changes in effective connectivity by propofol sedation.
AB  - Mechanisms of propofol-induced loss of consciousness remain poorly understood.
      Recent fMRI studies have shown decreases in functional connectivity during
      unconsciousness induced by this anesthetic agent. Functional connectivity does
      not provide information of directional changes in the dynamics observed during
      unconsciousness. The aim of the present study was to investigate, in healthy
      humans during an auditory task, the changes in effective connectivity resulting
      from propofol induced loss of consciousness. We used Dynamic Causal Modeling for
      fMRI (fMRI-DCM) to assess how causal connectivity is influenced by the anesthetic
      agent in the auditory system. Our results suggest that the dynamic observed in
      the auditory system during unconsciousness induced by propofol, can result in a
      mixture of two effects: a local inhibitory connectivity increase and a decrease
      in the effective connectivity in sensory cortices. 

PMID- 23977031
TI  - The earliest case of extreme sexual display with exaggerated male organs by two
      Middle Jurassic mecopterans.
AB  - BACKGROUND: Many extant male animals exhibit exaggerated body parts for display,
      defense or offence in sexual selection, such as male birds of paradise showing
      off colorful and elegant feathers and male moose and reindeers bearing large
      structured antlers. For insects, male rhinoceros and stag beetles have huge horn
      like structure for fighting and competition and some male Leptopanorpa
      scorpionflies have very long abdominal terminal segments for sexual display and
      competition. Fossil records of insects having exaggerated body parts for sexual
      display are fairly rare. One example is two male holcorpids with elongate
      abdominal segments from sixth (A6) to eighth (A8) and enlarged male genitalia
      from Eocene, suggesting evolution of these characters occurred fairly late.
      PRINCIPAL FINDINGS: We document two mecopterans with exaggerated male body parts
      from the late Middle Jurassic Jiulongshan Formation in northeastern China. Both
      have extremely extended abdominal segments from A6 to A8 and enlarged genitalia,
      which might have been used for sexual display and, to less extent, for fighting
      with other males in the competition for mates. Although Fortiholcorpa paradoxa
      gen. et sp. nov. and Miriholcorpa forcipata gen. et sp. nov. seem to have
      affinities with Holcorpidae, we deem both as Family Incertae sedis mainly due to
      significant differences in branching pattern of Media (M) veins and relative
      length of A8 for F. paradoxa, and indiscernible preservation of 5-branched M
      veins in hind wing for M. forcipata. CONCLUSIONS/SIGNIFICANCE: These two new taxa
      have extended the records of exaggerated male body parts of mecopterans for
      sexual display and/or selection from the Early Eocene to the late Middle
      Jurassic. The similar character present in some Leptopanorpa of Panorpidae
      suggests that the sexual display and/or sexual selection due to extremely
      elongated male abdominal and sexual organs outweigh the negative impact of bulky
      body and poor mobility in the evolutionary process.

PMID- 23977032
TI  - Single domain antibody multimers confer protection against rabies infection.
AB  - Post-exposure prophylactic (PEP) neutralizing antibodies against Rabies are the
      most effective way to prevent infection-related fatality. The outer envelope
      glycoprotein of the Rabies virus (RABV) is the most significant surface antigen
      for generating virus-neutralizing antibodies. The small size and uncompromised
      functional specificity of single domain antibodies (sdAbs) can be exploited in
      the fields of experimental therapeutic applications for infectious diseases
      through formatting flexibilities to increase their avidity towards target
      antigens. In this study, we used phage display technique to select and identify
      sdAbs that were specific for the RABV glycoprotein from a naive llama-derived
      antibody library. To increase their neutralizing potencies, the sdAbs were fused
      with a coiled-coil peptide derived from the human cartilage oligomeric matrix
      protein (COMP48) to form homogenous pentavalent multimers, known as combodies.
      Compared to monovalent sdAbs, the combodies, namely 26424 and 26434, exhibited
      high avidity and were able to neutralize 85-fold higher input of RABV (CVS-11
      strain) pseudotypes in vitro, as a result of multimerization, while retaining
      their specificities for target antigen. 26424 and 26434 were capable of
      neutralizing CVS-11 pseudotypes in vitro by 90-95% as compared to human rabies
      immunoglobulin (HRIG), currently used for PEP in Rabies. The multimeric sdAbs
      were also demonstrated to be partially protective for mice that were infected
      with lethal doses of rabies virus in vivo. The results demonstrate that the
      combodies could be valuable tools in understanding viral mechanisms, diagnosis
      and possible anti-viral candidate for RABV infection. 

PMID- 23977033
TI  - Association of genetic variation in adaptor protein APPL1/APPL2 loci with non
      alcoholic fatty liver disease.
AB  - The importance of genetics and epigenetic changes in the pathogenesis of non
      alcoholic fatty liver disease (NAFLD) has been increasingly recognized.
      Adiponectin has a central role in regulating glucose and lipid metabolism and
      controlling inflammation in insulin-sensitive tissues and low adiponectin levels
      have been linked to NAFLD. APPL1 and APPL2 are adaptor proteins that interact
      with the intracellular region of adiponectin receptors and mediate adiponectin
      signaling and its effects on metabolism. The aim of our study was the evaluation
      of a potential association between variants at APPL1 and APPL2 loci and NAFLD
      occurrence. The impact on liver damage and hepatic steatosis severity has been
      also evaluated. To this aim allele frequency and genotype distribution of APPL1-
      rs3806622 and -rs4640525 and APPL2-rs 11112412 variants were evaluated in 223
      subjects with clinical diagnosis of NAFLD and compared with 231 healthy subjects.
      The impact of APPL1 and APPL2 SNPs on liver damage and hepatic steatosis severity
      has been also evaluated. The minor-allele combination APPL1-C/APPL2-A was
      associated with an increased risk of NAFLD (OR = 2.50 95% CI 1.45-4.32; p<0.001)
      even after adjustment for age, sex, body mass index, insulin resistance (HOMA
      IR), triglycerides and adiponectin levels. This allele combination carrier had
      higher plasma alanine aminotransferase levels (Diff = 15.08 [7.60-22.57] p =
      0.001) and an increased frequency of severe steatosis compared to the reference
      allele combination (OR = 3.88; 95% CI 1.582-9.531; p<0.001). In conclusion, C
      APPL1/A-APPL2 allele combination is associated with NAFLD occurrence, with a more
      severe hepatic steatosis grade and with a reduced adiponectin cytoprotective
      effect on liver. 

PMID- 23977034
TI  - Diethylhexyl phthalates is associated with insulin resistance via oxidative
      stress in the elderly: a panel study.
AB  - BACKGROUND: Insulin resistance (IR) is believed to be the underlying mechanism of
      metabolic syndrome and type 2 diabetes mellitus (DM). Recently, a few studies
      have demonstrated that phthalates could cause oxidative stress which would
      contribute to the development of IR. Therefore, we evaluated whether exposure to
      phthalates affects IR, and oxidative stress is involved in the phthalates-IR
      pathway. METHODS: We recruited 560 elderly participants, and obtained blood and
      urine samples during repeated medical examinations. For the determination of
      phthalate exposure, we measured urinary levels of mono-(2-ethyl-5-hydroxyhexyl)
      phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) as metabolites
      of diethylhexyl phthalates (DEHP), and mono-n-butyl phthalate (MnBP) as a
      metabolite of di-butyl phthalate (DBP). Malondialdehyde (MDA), an oxidative
      stress biomarker, was also measured in urine samples. We measured serum levels of
      fasting glucose and insulin, and derived the homeostatic model assessment (HOMA)
      index to assess IR. A mixed-effect model and penalized regression spline were
      used to estimate the associations among phthalate metabolites, MDA, and IR.
      RESULTS: The molar sum of MEHHP and MEOHP (?DEHP) were significantly associated
      with HOMA (beta = 0.26, P = 0.040), and the association was apparent among
      participants with a history of DM (beta = 0.88, P = 0.037) and among females
      (beta = 0.30, P = 0.022). However, the relation between MnBP and HOMA was not
      found. When we evaluated whether oxidative stress is involved in increases of
      HOMA by ?DEHP, MDA levels were significantly associated with increases of ?DEHP
      (beta = 0.11, P<0.001) and HOMA (beta = 0.49, P = 0.049). CONCLUSIONS: Our study
      results suggest that exposure to DEHP in the elderly population increases IR,
      which is related with oxidative stress, and that participants with a history of
      DM and females are more susceptible to DEHP exposure.

PMID- 23977035
TI  - Evidence of dynamically dysregulated gene expression pathways in hyperresponsive
      B cells from African American lupus patients.
AB  - Recent application of gene expression profiling to the immune system has shown a
      great potential for characterization of complex regulatory processes. It is
      becoming increasingly important to characterize functional systems through
      multigene interactions to provide valuable insights into differences between
      healthy controls and autoimmune patients. Here we apply an original systematic
      approach to the analysis of changes in regulatory gene interconnections between
      in Epstein-Barr virus transformed hyperresponsive B cells from SLE patients and
      normal control B cells. Both traditional analysis of differential gene expression
      and analysis of the dynamics of gene expression variations were performed in
      combination to establish model networks of functional gene expression. This
      Pathway Dysregulation Analysis identified known transcription factors and
      transcriptional regulators activated uniquely in stimulated B cells from SLE
      patients. 

PMID- 23977036
TI  - Decreased autophagy contributes to myocardial dysfunction in rats subjected to
      nonlethal mechanical trauma.
AB  - Autophagy is important in cells for removing damaged organelles, such as
      mitochondria. Insufficient autophagy plays a critical role in tissue injury and
      organ dysfunction under a variety of pathological conditions. However, the role
      of autophagy in nonlethal traumatic cardiac damage remains unclear. The aims of
      the present study were to investigate whether nonlethal mechanical trauma may
      result in the change of cardiomyocyte autophagy, and if so, to determine whether
      the changed myocardial autophagy may contribute to delayed cardiac dysfunction.
      Male adult rats were subjected to nonlethal traumatic injury, and cardiomyocyte
      autophagy, cardiac mitochondrial function, and cardiac function in isolated
      perfused hearts were detected. Direct mechanical traumatic injury was not
      observed in the heart within 24 h after trauma. However, cardiomyocyte autophagy
      gradually decreased and reached a minimal level 6 h after trauma. Cardiac
      mitochondrial dysfunction was observed by cardiac radionuclide imaging 6 h after
      trauma, and cardiac dysfunction was observed 24 h after trauma in the isolated
      perfused heart. These were reversed when autophagy was induced by administration
      of the autophagy inducer rapamycin 30 min before trauma. Our present study
      demonstrated for the first time that nonlethal traumatic injury caused decreased
      autophagy, and decreased autophagy may contribute to post-traumatic organ
      dysfunction. Though our study has some limitations, it strongly suggests that
      cardiac damage induced by nonlethal mechanical trauma can be detected by
      noninvasive radionuclide imaging, and induction of autophagy may be a novel
      strategy for reducing posttrauma multiple organ failure. 

PMID- 23977037
TI  - Determination of neuraminidase kinetic constants using whole influenza virus
      preparations and correction for spectroscopic interference by a fluorogenic
      substrate.
AB  - The influenza neuraminidase (NA) enzyme cleaves terminal sialic acid residues
      from cellular receptors, a process required for the release of newly synthesized
      virions. A balance of NA activity with sialic acid binding affinity of
      hemagglutinin (HA) is important for optimal virus replication. NA sequence
      evolution through genetic shift and drift contributes to the continuous
      modulation of influenza virus fitness and pathogenicity. A simple and reliable
      method for the determination of kinetic parameters of NA activity could add
      significant value to global influenza surveillance and provide parameters for the
      projection of fitness and pathogenicity of emerging virus variants. The use of
      fluorogenic substrate 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid
      (MUNANA) and cell- or egg-grown whole influenza virus preparations have been
      attractive components of NA enzyme activity investigations. We describe important
      criteria to be addressed when determining K(m) and V(max) kinetic parameters
      using this method: (1) determination of the dynamic range of MUNANA and 4
      methylumbelliferone product (4-MU) fluorescence for the instrument used; (2)
      adjustment of reaction conditions to approximate initial rate conditions, i.e.
      <=15% of substrate converted during the reaction, with signal-to-noise ratio
      >=10; (3) correction for optical interference and inner filter effect caused by
      increasing concentrations of MUNANA substrate. The results indicate a significant
      interference of MUNANA with 4-MU fluorescence determination. The criteria
      proposed enable an improved rapid estimation of NA kinetic parameters and
      facilitate comparison of data between laboratories.

PMID- 23977038
TI  - Aerobic fitness in children and young adults with primary ciliary dyskinesia.
AB  - BACKGROUND: Although aerobic fitness is regarded as an overall prognostic measure
      of morbidity and mortality, its evaluation in the chronic progressive
      sinopulmonary disease primary ciliary dyskinesia (PCD) has been infrequently and
      inconsistently reported. Here we assessed peak oxygen uptake (VO2peak) in a large
      well-characterized cohort of PCD patients, and explored whether VO2peak was
      associated with parameters of pulmonary function, self-reported physical
      limitations, and physical activity level. METHODS: VO2peak, spirometry, diffusing
      capacity, whole-body plethysmography, and nitrogen multiple breath inert gas
      washout (N2 MBW) were assessed in a cross-sectional, single-occasion study of
      clinically stable children and young adults with PCD. We used a questionnaire
      including self-reported physical limitations in everyday life or in vigorous
      activities, and estimation of weekly hours of strenuous physical activity.
      VO2peak in PCD patients was compared with that in matched, healthy control
      subjects and a national reference. RESULTS: Forty-four PCD patients aged 6-29
      years exhibited reduced VO2peak compared to healthy controls (P<0.001) and the
      national reference. VO2peak was abnormal (z-score <-1.96) in 34% of PCD patients.
      Spirometric values, RV/TLC, and indices of N2 MBW were significantly abnormal,
      but VO2peak only correlated with FEV1 and DLCO/VA. VO2peak correlated with
      complaints of moderate or significant limitations in vigorous activities (P =
      0.0001), exhibited by 39% of PCD patients. CONCLUSION: One-third of PCD patients
      exhibited substantially lower aerobic fitness than healthy subjects. Aerobic
      fitness correlated with FEV1, DLCO/VA and self-reported complaints of limitations
      in vigorous physical activity. These findings are most likely explained by PCD
      pulmonary disease and its impact on pulmonary function and physical ability.
      Considering fitness as an important outcome and including regular strenuous
      physical activity in PCD treatment would probably altogether increase pulmonary
      clearance, lung function, aerobic fitness, and quality of life, and prevent
      lifestyle-related diseases.

PMID- 23977039
TI  - Neurobehavioral toxicity of a repeated exposure (14 days) to the airborne
      polycyclic aromatic hydrocarbon fluorene in adult Wistar male rats.
AB  - Fluorene is one of the most abundant polycyclic aromatic hydrocarbons in air and
      may contribute to the neurobehavioral alterations induced by the environmental
      exposure of humans to PAHs. Since no data are available on fluorene
      neurotoxicity, this study was conducted in adult rats to assess the behavioral
      toxicity of repeated fluorene inhalation exposure. Male rats (n = 18/group) were
      exposed nose-only to 1.5 or 150 ppb of fluorene 6 hours/day for 14 consecutive
      days, whereas the control animals were exposed to non-contaminated air. At the
      end of the exposure, animals were tested for activity and anxiety in an open
      field and in an elevated-plus maze, for short-term memory in a Y-maze, and for
      spatial learning in an eight-arm maze. The results showed that the locomotor
      activity and the learning performances of the animals were unaffected by
      fluorene. In parallel, the fluorene-exposed rats showed a lower level of anxiety
      than controls in the open-field, but not in the elevated-plus maze, which is
      probably due to a possible difference in the aversive feature of the two mazes.
      In the same animals, increasing blood and brain levels of fluorene
      monohydroxylated metabolites (especially the 2-OH fluorene) were detected at both
      concentrations (1.5 and 150 ppb), demonstrating the exposure of the animals to
      the pollutant and showing the ability of this compound to be metabolized and to
      reach the cerebral compartment. The present study highlights the possibility for
      a 14-day fluorene exposure to induce some specific anxiety-related behavioral
      disturbances, and argues in favor of the susceptibility of the adult brain when
      exposed to volatile fluorene. 

PMID- 23977040
TI  - Cooperation in health: mapping collaborative networks on the web.
AB  - OBJECTIVE: To map and investigate the relationships established on the web
      between leading health-research institutions around the world. METHODS: Sample
      selection was based on the World Health Organization (WHO) Collaborating Centres
      (CCs). Data on the 768 active CCs in 89 countries were retrieved from the WHO's
      database. The final sample consisted of 190 institutions devoted to health
      sciences in 42 countries. Data on each institution's website were retrieved using
      webometric techniques (interlinking), and an asymmetric matrix was generated for
      social network analysis. FINDINGS: The results showed that American and European
      institutions, such as the Centers for Disease Control and Prevention (CDC), the
      National Institutes of Health (NIH) and the National Institute of Health and
      Medical Research (INSERM), are the most highly connected on the web and have a
      higher capacity to attract hyperlinks. The Karolinska Institute (KI-SE) in Sweden
      is well placed as an articulation point between several integrants of the network
      and the component's core but lacks general recognition on the web by hyperlinks.
      Regarding the north-south divide, Mexico and Brazil appear to be key southern
      players on the web. The results showed that the hyperlinks exchanged between
      northern and southern countries present an abysmal gap: 99.49% of the hyperlinks
      provided by the North are directed toward the North itself, in contrast to 0.51%
      that are directed toward the South. Regarding the South, its institutions are
      more connected to its northern partners, with 98.46% of its hyperlinks directed
      toward the North, and mainly toward the United States, compared with 1.54% toward
      southern neighbors. CONCLUSION: It is advisable to strengthen integration
      policies on the web and to increase web networking through hyperlink exchange. In
      this way, the web could actually reflect international cooperation in health and
      help to legitimize and enhance the visibility of the many existing south-south
      collaboration networks.

PMID- 23977041
TI  - Case report evidence of relationships between hepatocellular carcinoma and
      ochratoxicosis.
AB  - PURPOSE: The incidence of Hepatocellular carcinoma (HCC) is on the rise, but what
      is causing that trend has remained a mystery. Mycotoxins are almost entirely
      ignored health problems, and sometimes actually naively belittled in advanced
      medical care. Ochratoxin A (OTA) is one of the most abundant food contaminating
      mycotoxins worldwide that is carcinogenic, but no studies have evaluated its
      levels in HCC patients. Therefore, this study was designed to monitor the
      presence of OTA in the serum of HCC patients and to quantify the strength of the
      association between OTA and HCC. METHODS: We conducted a case control-based study
      on 61 participants. Thirty-nine were HCC cases identified between 2010 and 2012
      and individually matched by age, sex, residence and date of recruitment to 22
      healthy controls. Serum OTA and alpha-fetoprotein levels were measured by using
      high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent
      assay, respectively. RESULTS: HPLC analysis of 61 serum samples indicated that
      the highest incidence of elevated OTA was found in the HCC group and was 5-fold
      higher than in the control group. The concentration of OTA in the HCC group
      ranged between 0.129 and 10.93 ng/mL with a mean value+/-SD of 1.1+/-0.3 ng/mL,
      while in the normal group it ranged between 0.005 and 0.50 ng/mL with a mean
      value+/-SD of 0.201+/-0.02 ng/mL. The odds ratio for HCC patients presenting OTA
      levels above the cut-off of 0.207 (calculated by the receiver operating
      characteristic curve) was 9.78 (95% confidence interval = 2.9095-32.9816, P =
      0.0002) with respect to normal controls, suggesting that HCC is 9.8 times as
      frequent in the exposed group to OTA. CONCLUSION: Our results reveal a strong
      association between the presence of OTA and HCC, which may offer a coherent
      explanation for much of the descriptive epidemiology of HCC and suggest new
      avenues for analytical research.

PMID- 23977042
TI  - Analysis of genome-wide changes in the translatome of Arabidopsis seedlings
      subjected to heat stress.
AB  - Heat stress is one of the most prominent and deleterious environmental threats
      affecting plant growth and development. Upon high temperatures, plants launch
      specialized gene expression programs that promote stress protection and survival.
      These programs involve global and specific changes at the transcriptional and
      translational levels. However, the coordination of these processes and their
      specific role in the establishment of the heat stress response is not fully
      elucidated. We have carried out a genome-wide analysis to monitor the changes in
      the translation efficiency of individual mRNAs of Arabidopsis thaliana seedlings
      after the exposure to a heat shock stress. Our results demonstrate that
      translation exerts a wide but dual regulation of gene expression. For the
      majority of mRNAs, translation is severely repressed, causing a decreased of 50%
      in the association of the bulk of mRNAs to polysomes. However, some relevant
      mRNAs involved in different aspects of homeostasis maintenance follow a
      differential pattern of translation. Sequence analyses of the differentially
      translated mRNAs unravels that some features, such as the 5'UTR G+C content and
      the cDNA length, may take part in the discrimination mechanisms for mRNA polysome
      loading. Among the differentially translated genes, master regulators of the
      stress response stand out, highlighting the main role of translation in the early
      establishment of the physiological response of plants to elevated temperatures. 

PMID- 23977043
TI  - No control genes required: Bayesian analysis of qRT-PCR data.
AB  - BACKGROUND: Model-based analysis of data from quantitative reverse-transcription
      PCR (qRT-PCR) is potentially more powerful and versatile than traditional
      methods. Yet existing model-based approaches cannot properly deal with the higher
      sampling variances associated with low-abundant targets, nor do they provide a
      natural way to incorporate assumptions about the stability of control genes
      directly into the model-fitting process. RESULTS: In our method, raw qPCR data
      are represented as molecule counts, and described using generalized linear mixed
      models under Poisson-lognormal error. A Markov Chain Monte Carlo (MCMC) algorithm
      is used to sample from the joint posterior distribution over all model
      parameters, thereby estimating the effects of all experimental factors on the
      expression of every gene. The Poisson-based model allows for the correct
      specification of the mean-variance relationship of the PCR amplification process,
      and can also glean information from instances of no amplification (zero counts).
      Our method is very flexible with respect to control genes: any prior knowledge
      about the expected degree of their stability can be directly incorporated into
      the model. Yet the method provides sensible answers without such assumptions, or
      even in the complete absence of control genes. We also present a natural Bayesian
      analogue of the "classic" analysis, which uses standard data pre-processing steps
      (logarithmic transformation and multi-gene normalization) but estimates all gene
      expression changes jointly within a single model. The new methods are
      considerably more flexible and powerful than the standard delta-delta Ct analysis
      based on pairwise t-tests. CONCLUSIONS: Our methodology expands the applicability
      of the relative-quantification analysis protocol all the way to the lowest
      abundance targets, and provides a novel opportunity to analyze qRT-PCR data
      without making any assumptions concerning target stability. These procedures have
      been implemented as the MCMC.qpcr package in R.

PMID- 23977044
TI  - Contribution of Donana wetlands to carbon sequestration.
AB  - Inland and transitional aquatic systems play an important role in global carbon
      (C) cycling. Yet, the C dynamics of wetlands and floodplains are poorly defined
      and field data is scarce. Air-water CO2 fluxes in the wetlands of Donana Natural
      Area (SW Spain) were examined by measuring alkalinity, pH and other
      physiochemical parameters in a range of water bodies during 2010-2011. Areal
      fluxes were calculated and, using remote sensing, an estimate of the contribution
      of aquatic habitats to gaseous CO2 transport was derived. Semi-permanent ponds
      adjacent to the large Guadalquivir estuary acted as mild sinks, whilst temporal
      wetlands were strong sources of CO2 (-0.8 and 36.3 mmol(CO2) m(-2) d(-1)). Fluxes
      in semi-permanent streams and ponds changed seasonally; acting as sources in
      spring-winter and mild sinks in autumn (16.7 and -1.2 mmol(CO2) m(-2) d(-1)).
      Overall, Donana's water bodies were a net annual source of CO2 (5.2 mol(C) m(-2)
      y(-1). Up-scaling clarified the overwhelming contribution of seasonal flooding
      and allochthonous organic matter inputs in determining regional air-water gaseous
      CO2 transport (13.1 Gg(C) y(-1)). Nevertheless, this estimate is about 6 times <
      local marsh net primary production, suggesting the system acts as an annual net
      CO2 sink. Initial indications suggest longer hydroperiods may favour
      autochthonous C capture by phytoplankton. Direct anthropogenic impacts have
      reduced the hydroperiod in Donana and this maybe exacerbated by climate change
      (less rainfall and more evaporation), suggesting potential for the modification
      of C sequestration.

PMID- 23977045
TI  - Improving metabolic health in obese male mice via diet and exercise restores
      embryo development and fetal growth.
AB  - Paternal obesity is now clearly associated with or causal of impaired embryo and
      fetal development and reduced pregnancy rates in humans and rodents. This appears
      to be a result of reduced blastocyst potential. Whether these adverse embryo and
      fetal outcomes can be ameliorated by interventions to reduce paternal obesity has
      not been established. Here, male mice fed a high fat diet (HFD) to induce obesity
      were used, to determine if early embryo and fetal development is improved by
      interventions of diet (CD) and/or exercise to reduce adiposity and improve
      metabolism. Exercise and to a lesser extent CD in obese males improved embryo
      development rates, with increased cell to cell contacts in the compacting embryo
      measured by E-cadherin in exercise interventions and subsequently, increased
      blastocyst trophectoderm (TE), inner cell mass (ICM) and epiblast cell numbers.
      Implantation rates and fetal development from resulting blastocysts were also
      improved by exercise in obese males. Additionally, all interventions to obese
      males increased fetal weight, with CD alone and exercise alone, also increasing
      fetal crown-rump length. Measures of embryo and fetal development correlated with
      paternal measures of glycaemia, insulin action and serum lipids regardless of
      paternal adiposity or intervention, suggesting a link between paternal metabolic
      health and subsequent embryo and fetal development. This is the first study to
      show that improvements to metabolic health of obese males through diet and
      exercise can improve embryo and fetal development, suggesting such interventions
      are likely to improve offspring health. 

PMID- 23977046
TI  - Large scale comparison of gene expression levels by microarrays and RNAseq using
      TCGA data.
AB  - RNAseq and microarray methods are frequently used to measure gene expression
      level. While similar in purpose, there are fundamental differences between the
      two technologies. Here, we present the largest comparative study between
      microarray and RNAseq methods to date using The Cancer Genome Atlas (TCGA) data.
      We found high correlations between expression data obtained from the Affymetrix
      one-channel microarray and RNAseq (Spearman correlations coefficients of ~0.8).
      We also observed that the low abundance genes had poorer correlations between
      microarray and RNAseq data than high abundance genes. As expected, due to
      measurement and normalization differences, Agilent two-channel microarray and
      RNAseq data were poorly correlated (Spearman correlations coefficients of only
      ~0.2). By examining the differentially expressed genes between tumor and normal
      samples we observed reasonable concordance in directionality between Agilent two
      channel microarray and RNAseq data, although a small group of genes were found to
      have expression changes reported in opposite directions using these two
      technologies. Overall, RNAseq produces comparable results to microarray
      technologies in term of expression profiling. The RNAseq normalization methods
      RPKM and RSEM produce similar results on the gene level and reasonably concordant
      results on the exon level. Longer exons tended to have better concordance between
      the two normalization methods than shorter exons. 

PMID- 23977048
TI  - Willingness to use the Internet to seek information on HIV prevention and care
      among men who have sex with men in Ho Chi Minh City, Vietnam.
AB  - BACKGROUND: In Vietnam, men who have sex with men (MSM) are highly affected by
      HIV and need new targeted HIV prevention strategies. OBJECTIVES: To assess the
      willingness to use the Internet to seek information on HIV prevention and care
      and associated factors among MSM in Ho Chi Minh City. METHODS: A descriptive
      cross-sectional study was conducted in 2012. Participants were recruited using a
      convenience sampling method in venues most frequented by MSM and completed a self
      administered questionnaire. Logistic regression models were performed to estimate
      factors associated with the willingness to use the Internet to seek information
      on HIV prevention and care. RESULTS: A total of 358 MSM were approached for the
      survey and 222 questionnaires (62.0%) were eligible for analyses. Overall, 76.1%
      of the respondents reported that they were willing to use the Internet to seek
      information on HIV prevention and care. A number of male partners in last year
      less than or equal to 3 (Adjusted Odds Ratio: 3.07, 95% Confidence interval: 1.40
      6.73), a history of STI screening (4.10, 1.02-16.48) and HIV testing (3.23, 1.20
      8.64) and having ever sought a male sexual partner through the Internet (3.56,
      1.55-8.18) were significantly positively associated with the willingness to use
      the Internet to seek information on HIV prevention and care. CONCLUSION: The MSM
      interviewed in Ho Chi Minh City reported a high willingness to use the Internet
      to seek information on HIV prevention and care. In a context where new media are
      increasingly considered as promising options for reaching this HIV risk group,
      further research should be conducted on developing and testing tailored online
      tools adapted to the needs of Vietnamese MSM.

PMID- 23977047
TI  - Nurr1 represses tyrosine hydroxylase expression via SIRT1 in human neural stem
      cells.
AB  - Nurr1 is an orphan nuclear receptor best known for its essential role in the
      development and maintenance of midbrain dopaminergic (DA) neurons. During DA
      neurogenesis, Nurr1 directly targets human tyrosine hydroxylase (hTH). Here we
      investigated this targeting to identify the molecular mechanisms by which Nurr1
      regulates DA neurogenesis. We previously cloned the hTH promoter and found three
      consensus elements for Nurr1 binding: NBRE-A, -B, and -C. In the present study,
      gel retardation and luciferase assays using hTH constructs showed that Nurr1
      preferentially bound to NBRE-A, through which it mediated transcriptional
      activity. Furthermore, Nurr1 displayed dual-function transcriptional activities
      depending on the cell type. In DA-like SH-SY5Y cells, Nurr1 dose-dependently
      stimulated hTH-3174 promoter activity by 7- to 11-fold. However, in the human
      neural stem cell (hNSC) line HB1.F3, Nurr1 strongly repressed transcription from
      the same promoter. This repression was relieved by mutation of only the NBRE-A
      element and by nicotinamide [an inhibitor of class III histone deacetylases
      (HDACs), such as SIRT1], but not by trichostatin A (an inhibitor of class I and
      II HDACs). SIRT1 was strongly expressed in the nucleus of HB1.F3 cells, while it
      was localized in the cytoplasm in SH-SY5Y cells. ChIP assays of HB1.F3 cells
      showed that Nurr1 overexpression significantly increased the SIRT1 occupancy of
      the NBRE-A hTH promoter region, while low SIRT1 levels were observed in control
      cells. In contrast, no significant SIRT1 recruitment was observed in SH-SY5Y
      cells. These results indicate that differential SIRT1 localization may be
      involved in hTH gene regulation. Overall, our findings suggest that Nurr1 exists
      in dual transcriptional complexes, including co-repressor complexes that can be
      remodeled to become co-activators and can fine-tune hTH gene transcription during
      human DA neurogenesis. 

PMID- 23977049
TI  - Disparity and convergence: Chinese provincial government health expenditures.
AB  - The huge regional disparity in government health expenditures (GHE) is a major
      policy concern in China. This paper addresses whether provincial GHE converges in
      China from 1997 to 2009 using the economic convergence framework based on
      neoclassical economic growth theory. Our empirical investigation provides
      compelling evidence of long-term convergence in provincial GHE within China, but
      not in short-term. Policy implications of these empirical results are discussed. 

PMID- 23977050
TI  - Clinical and epidemiologic characteristics of norovirus GII.4 Sydney during
      winter 2012-13 in Beijing, China following its global emergence.
AB  - BACKGROUND: Limited information is available on the molecular epidemiology of
      GII.4 Sydney-associated diarrhea in China in the winter of 2012-13 during the
      global epidemic associated with the emergence of GII.4 Sydney. METHODS: Fecal
      specimens collected from 171 diarrhea outpatients (one from each) between late
      October 2012 and the middle of March 2013 were examined for NoV by reverse
      transcription-polymerase chain reaction and sequences corresponding to both the
      NoV partial polymerase and partial capsid regions were analyzed phylogenetically.
      Clinical characteristics of GII.4 Sydney cases versus other NoV-positive cases
      detected in a previous study were compared statistically. RESULTS: Twenty-six
      (15.2%, 26/171) outpatients with diarrhea were infected with NoV. Twenty-two of
      the 26 (84.6%) identified NoV strains clustered into GII.4 Sydney. There was a
      significant difference in symptoms of fever (chi(2), P<0.05 ), abdominal pain
      (chi(2), P<0.05 ) and diarrhea frequency (Mann-Whitney U test, P<0.05) between
      the GII.4 Sydney case group and other NoV-positive case group. CONCLUSIONS: The
      new NoV variant, GII.4 Sydney, has been circulating in Beijing, China and became
      the predominant strain in the winter of 2012-13. GII.4 Sydney causes severe
      fever, abdominal pain and higher diarrhea frequency clinically compared to other
      NoV infections.

PMID- 23977051
TI  - alphaV-integrins are required for mechanotransduction in MDCK epithelial cells.
AB  - The properties of epithelial cells within tissues are regulated by their
      immediate microenvironment, which consists of neighboring cells and the
      extracellular matrix (ECM). Integrin heterodimers orchestrate dynamic assembly
      and disassembly of cell-ECM connections and thereby convey biochemical and
      mechanical information from the ECM into cells. However, the specific
      contributions and functional hierarchy between different integrin heterodimers in
      the regulation of focal adhesion dynamics in epithelial cells are incompletely
      understood. Here, we have studied the functions of RGD-binding alphaV-integrins
      in a Madin Darby Canine Kidney (MDCK) cell model and found that alphaV-integrins
      regulate the maturation of focal adhesions (FAs) and cell spreading. alphaV
      integrin-deficient MDCK cells bound collagen I (Col I) substrate via alpha2beta1
      integrins but failed to efficiently recruit FA components such as talin, focal
      adhesion kinase (FAK), vinculin and integrin-linked kinase (ILK). The apparent
      inability to mature alpha2beta1-integrin-mediated FAs and link them to cellular
      actin cytoskeleton led to disrupted mechanotransduction in alphaV-integrin
      deficient cells seeded onto Col I substrate. 

PMID- 23977052
TI  - Identification of estrogen receptor-related receptor gamma as a direct
      transcriptional target of angiogenin.
AB  - Nuclear translocation of angiogenin (ANG) is essential for the proliferation of
      its target cells. ANG promotes rRNA synthesis, while whether it regulates mRNA
      transcription remains unknown. Using the chromatin immunoprecipitation method, we
      have identified 12 ANG-binding sequences. One of these sequences lies in the
      estrogen receptor-related receptor gamma (ERRgamma) gene which we designated as
      ANG-Binding Sequence within ERRgamma (ABSE). ABSE exhibited ANG-dependent
      repressor activity in the luciferase reporter system. Down-regulation of ANG
      increased ERRgamma expression, and active gene marker level at the ABSE region.
      The expression levels of ERRgamma targets genes, p21(WAF/CIP) and p27(KIP1), and
      the occupation of ERRgamma on their promoter regions were increased in ANG
      deficient cells accordingly. Furthermore, knockdown of ERRgamma promoted the
      proliferation rate in ANG-deficient breast cancer cells. Finally,
      immunohistochemistry staining showed negative correlation between ANG and
      ERRgamma in breast cancer tissue. Altogether, our study provides evidence that
      nuclear ANG directly binds to the ABSE of ERRgamma gene and inhibits ERRgamma
      transcription to promote breast cancer cell proliferation. 

PMID- 23977053
TI  - FRAP analysis reveals stabilization of adhesion structures in the epidermis
      compared to cultured keratinocytes.
AB  - Proper development and tissue maintenance requires cell-cell adhesion structures,
      which serve diverse and crucial roles in tissue morphogenesis. Epithelial tissues
      have three main types of cell-cell junctions: tight junctions, which play a major
      role in barrier formation, and adherens junctions and desmosomes, which provide
      mechanical stability and organize the underlying cytoskeleton. Our current
      understanding of adhesion function is hindered by a lack of tools and methods to
      image junctions in mammals. To better understand the dynamics of adhesion in
      tissues we have created a knock-in ZO-1-GFP mouse and a BAC-transgenic mouse
      expressing desmoplakin I-GFP. We performed fluorescence recovery after
      photobleaching (FRAP) experiments to quantify the turnover rates of the tight
      junction protein ZO-1, the adherens junction protein E-cadherin, and the
      desmosomal protein desmoplakin in the epidermis. Proteins at each type of
      junction are remarkably stable in the epidermis, in contrast to the high observed
      mobility of E-cadherin and ZO-1 at adherens junctions and tight junctions,
      respectively, in cultured cells. Our data demonstrate that there are additional
      mechanisms for stabilizing junctions in tissues that are not modeled by cell
      culture. 

PMID- 23977054
TI  - Effects of feed contaminant deoxynivalenol on plasma cytokines and mRNA
      expression of immune genes in the intestine of broiler chickens.
AB  - An experiment was conducted to investigate the individual and combined effects of
      dietary deoxynivalenol (DON) and a microbial feed additive on plasma cytokine
      level and on the expression of immune relevant genes in jejunal tissues of
      broilers. A total of 40 broiler chicks were obtained from a commercial hatchery
      and divided randomly into four groups (10 birds per group). Birds were reared in
      battery cages from one day old for 5 weeks. The dietary groups were 1) control
      birds fed basal diet; 2) DON group fed basal diet contaminated with 10 mg DON/ kg
      feed; 3) DON + Mycofix group fed basal diet contaminated with 10 mg DON/ kg feed
      and supplemented with a commercial feed additive, Mycofix(r) Select (MS) (2.5
      kg/ton of feed); 4) Mycofix group fed basal diet supplemented with MS (2.5 kg/ton
      of feed). At 35 days, the plasma levels of tumor necrosis factor alpha (TNF
      alpha) and interleukin 8 (IL-8) were quantified by ELISA test kits. Furthermore,
      the mRNA expression of TNF-alpha, IL-8, IL-1beta, interferon gamma (IFNgamma),
      transforming growth factor beta receptor I (TGFBR1) and nuclear factor kappa
      light-chain-enhancer of activated B cells 1 (NF-kappabeta1) in jejunum were
      quantified by qRT-PCR. The results showed that the plasma TNF-alpha decreased in
      response to DON, while in combination with MS, the effect of DON was reduced. DON
      down-regulated the relative gene expression of IL-1beta, TGFBR1 and IFN-gamma,
      and addition of MS to the DON contaminated diet compensates these effects on IL
      1beta, TGFBR1 but not for IFN-gamma. Furthermore, supplementation of MS to either
      DON contaminated or control diet up-regulated the mRNA expression of NF
      kappabeta1. In conclusion, DON has the potential to provoke and modulate
      immunological reactions of broilers and subsequently could increase their
      susceptibility to disease. The additive seemed to have almost as much of an
      effect as DON, albeit on different genes. 

PMID- 23977056
TI  - Novel genetic analysis for case-control genome-wide association studies:
      quantification of power and genomic prediction accuracy.
AB  - Genome-wide association studies (GWAS) are routinely conducted for both
      quantitative and binary (disease) traits. We present two analytical tools for use
      in the experimental design of GWAS. Firstly, we present power calculations
      quantifying power in a unified framework for a range of scenarios. In this
      context we consider the utility of quantitative scores (e.g. endophenotypes) that
      may be available on cases only or both cases and controls. Secondly, we consider,
      the accuracy of prediction of genetic risk from genome-wide SNPs and derive an
      expression for genomic prediction accuracy using a liability threshold model for
      disease traits in a case-control design. The expected values based on our derived
      equations for both power and prediction accuracy agree well with observed
      estimates from simulations. 

PMID- 23977055
TI  - Cardiac Per2 functions as novel link between fatty acid metabolism and myocardial
      inflammation during ischemia and reperfusion injury of the heart.
AB  - Disruption of peripheral circadian rhyme pathways dominantly leads to metabolic
      disorders. Studies on circadian rhythm proteins in the heart indicated a role for
      Clock or Per2 in cardiac metabolism. In contrast to Clock(-/-), Per2(-/-) mice
      have larger infarct sizes with deficient lactate production during myocardial
      ischemia. To test the hypothesis that cardiac Per2 represents an important
      regulator of cardiac metabolism during myocardial ischemia, we measured lactate
      during reperfusion in Per1(-/-), Per2(-/-) or wildtype mice. As lactate
      measurements in whole blood indicated an exclusive role of Per2 in controlling
      lactate production during myocardial ischemia, we next performed gene array
      studies using various ischemia-reperfusion protocols comparing wildtype and Per2(
      /-) mice. Surprisingly, high-throughput gene array analysis revealed dominantly
      lipid metabolism as the differentially regulated pathway in wildtype mice when
      compared to Per2(-/-). In all ischemia-reperfusion protocols used, the enzyme
      enoyl-CoA hydratase, which is essential in fatty acid beta-oxidation, was
      regulated in wildtype animals only. Studies using nuclear magnet resonance
      imaging (NMRI) confirmed altered fatty acid populations with higher mono
      unsaturated fatty acid levels in hearts from Per2(-/-) mice. Unexpectedly,
      studies on gene regulation during reperfusion revealed solely pro inflammatory
      genes as differentially regulated 'Per2-genes'. Subsequent studies on
      inflammatory markers showed increasing IL-6 or TNFalpha levels during reperfusion
      in Per2(-/-) mice. In summary, these studies reveal an important role of cardiac
      Per2 for fatty acid metabolism and inflammation during myocardial ischemia and
      reperfusion, respectively.

PMID- 23977057
TI  - Diseases in patients coming to a sleep center with symptoms related to restless
      legs syndrome.
AB  - STUDY OBJECTIVE: To explore the profile of patients who visit a sleep center with
      symptoms that fulfill the four essential criteria for restless legs syndrome
      (RLS). DESIGN: A prospective study. SETTING: Outpatients from one sleep disorders
      clinic in Taiwan. PARTICIPANTS: 1,200 consecutive patients visit sleep disorders
      clinic with any sleep complaints. INTERVENTIONS: After completing a history and
      physical examination, all participants answered the RLS questionnaire. Subjects
      who fulfilled the four essential criteria for RLS were referred to a special
      clinic. A work-up including blood tests, polysomnography, and specialized
      neurological tests etc. was performed to make the final diagnosis. MEASUREMENTS
      AND RESULTS: A total of 1,185 participants were enrolled, and, of these,
      131(11.1%) fulfilled the four essential criteria for RLS, and 121 completed the
      supplemental work-up. Their mean age was 47.6+/-13.3 and 52.9% were male.
      Insomnia and snoring were the most common chief complaints. Obstructive sleep
      apnea syndrome and other diseases were found in 103 patients. Only 18 (14.9%)
      patients had no comorbid condition and were diagnosed with primary RLS.
      CONCLUSIONS: Symptoms of RLS are common in patients with sleep complaints. Even
      in a sleep clinic, using a questionnaire approach for identification of RLS has a
      low positive predictive value. Clinicians should pay attention to the limitations
      of the 4-item questionnaire in diagnosis of RLS and also the importance of a
      careful differential diagnosis to identify possible secondary causes of RLS.

PMID- 23977058
TI  - Three-dimensional vertebral wedging in mild and moderate adolescent idiopathic
      scoliosis.
AB  - BACKGROUND: Vertebral wedging is associated with spinal deformity progression in
      adolescent idiopathic scoliosis. Reporting frontal and sagittal wedging
      separately could be misleading since these are projected values of a single three
      dimensional deformation of the vertebral body. The objectives of this study were
      to determine if three-dimensional vertebral body wedging is present in mild
      scoliosis and if there are a preferential vertebral level, position and plane of
      deformation with increasing scoliotic severity. METHODOLOGY: Twenty-seven
      adolescent idiopathic scoliotic girls with mild to moderate Cobb angles (10
      degrees  to 50 degrees ) participated in this study. All subjects had at least
      one set of bi-planar radiographs taken with the EOS(r) X-ray imaging system prior
      to any treatment. Subjects were divided into two groups, separating the mild
      (under 20 degrees ) from the moderate (20 degrees  and over) spinal scoliotic
      deformities. Wedging was calculated in three different geometric planes with
      respect to the smallest edge of the vertebral body. RESULTS: Factorial analyses
      of variance revealed a main effect for the scoliosis severity but no main effect
      of vertebral Levels (apex and each of the three vertebrae above and below it) (F
      = 1.78, p = 0.101). Main effects of vertebral Positions (apex and above or below
      it) (F = 4.20, p = 0.015) and wedging Planes (F = 34.36, p<0.001) were also
      noted. Post-hoc analysis demonstrated a greater wedging in the inferior group of
      vertebrae (3.6 degrees ) than the superior group (2.9 degrees , p = 0.019) and a
      significantly greater wedging (p<=0.03) along the sagittal plane (4.3 degrees ).
      CONCLUSIONS: Vertebral wedging was present in mild scoliosis and increased as the
      scoliosis progressed. The greater wedging of the inferior group of vertebrae
      could be important in estimating the most distal vertebral segment to be
      restrained by bracing or to be fused in surgery. Largest vertebral body wedging
      values obtained in the sagittal plane support the claim that scoliosis could be
      initiated through a hypokyphosis.

PMID- 23977059
TI  - Biophysical constraints on optimal patch lengths for settlement of a reef
      building bivalve.
AB  - Reef-building species form discrete patches atop soft sediments, and reef
      restoration often involves depositing solid material as a substrate for larval
      settlement and growth. There have been few theoretical efforts to optimize the
      physical characteristics of a restored reef patch to achieve high recruitment
      rates. The delivery of competent larvae to a reef patch is influenced by larval
      behavior and by physical habitat characteristics such as substrate roughness,
      patch length, current speed, and water depth. We used a spatial model, the
      "hitting-distance" model, to identify habitat characteristics that will jointly
      maximize both the settlement probability and the density of recruits on an oyster
      reef (Crassostrea virginica). Modeled larval behaviors were based on laboratory
      observations and included turbulence-induced diving, turbulence-induced passive
      sinking, and neutral buoyancy. Profiles of currents and turbulence were based on
      velocity profiles measured in coastal Virginia over four different substrates:
      natural oyster reefs, mud, and deposited oyster and whelk shell. Settlement
      probabilities were higher on larger patches, whereas average settler densities
      were higher on smaller patches. Larvae settled most successfully and had the
      smallest optimal patch length when diving over rough substrates in shallow water.
      Water depth was the greatest source of variability, followed by larval behavior,
      substrate roughness, and tidal current speed. This result suggests that the best
      way to maximize settlement on restored reefs is to construct patches of optimal
      length for the water depth, whereas substrate type is less important than
      expected. Although physical patch characteristics are easy to measure,
      uncertainty about larval behavior remains an obstacle for predicting settlement
      patterns. The mechanistic approach presented here could be combined with a
      spatially explicit metapopulation model to optimize the arrangement of reef
      patches in an estuary or region for greater sustainability of restored habitats. 

PMID- 23977060
TI  - Genome-wide association study reveals genetic architecture of eating behavior in
      pigs and its implications for humans obesity by comparative mapping.
AB  - This study was aimed at identifying genomic regions controlling feeding behavior
      in Danish Duroc boars and its potential implications for eating behavior in
      humans. Data regarding individual daily feed intake (DFI), total daily time spent
      in feeder (TPD), number of daily visits to feeder (NVD), average duration of each
      visit (TPV), mean feed intake per visit (FPV) and mean feed intake rate (FR) were
      available for 1130 boars. All boars were genotyped using the Illumina Porcine
      SNP60 BeadChip. The association analyses were performed using the GenABEL package
      in the R program. Sixteen SNPs were found to have moderate genome-wide
      significance (p<5E-05) and 76 SNPs had suggestive (p<5E-04) association with
      feeding behavior traits. MSI2 gene on chromosome (SSC) 14 was very strongly
      associated with NVD. Thirty-six SNPs were located in genome regions where QTLs
      have previously been reported for behavior and/or feed intake traits in pigs. The
      regions: 64-65 Mb on SSC 1, 124-130 Mb on SSC 8, 63-68 Mb on SSC 11, 32-39 Mb and
      59-60 Mb on SSC 12 harbored several signifcant SNPs. Synapse genes (GABRR2,
      PPP1R9B, SYT1, GABRR1, CADPS2, DLGAP2 and GOPC), dephosphorylation genes (PPM1E,
      DAPP1, PTPN18, PTPRZ1, PTPN4, MTMR4 and RNGTT) and positive regulation of peptide
      secretion genes (GHRH, NNAT and TCF7L2) were highly significantly associated with
      feeding behavior traits. This is the first GWAS to identify genetic variants and
      biological mechanisms for eating behavior in pigs and these results are important
      for genetic improvement of pig feed efficiency. We have also conducted pig-human
      comparative gene mapping to reveal key genomic regions and/or genes on the human
      genome that may influence eating behavior in human beings and consequently affect
      the development of obesity and metabolic syndrome. This is the first
      translational genomics study of its kind to report potential candidate genes for
      eating behavior in humans. 

PMID- 23977061
TI  - Regulation of cell wall synthesis by the clathrin light chain is essential for
      viability in Schizosaccharomyces pombe.
AB  - The regulation of cell wall synthesis by the clathrin light chain has been
      addressed. Schizosaccharomyces pombe clc1Delta mutant was inviable in the absence
      of osmotic stabilization; when grown in sorbitol-supplemented medium clc1Delta
      cells grew slowly, formed aggregates, and had strong defects in morphology.
      Additionally, clc1Delta cells exhibited an altered cell wall composition. A
      mutant that allowed modulating the amount of Clc1p was created to analyze in more
      detail the dependence of cell wall synthesis on clathrin. A 40% reduction in the
      amount of Clc1p did not affect acid phosphatase secretion and bulk lipid
      internalization. Under these conditions, beta(1,3)glucan synthase activity and
      cell wall synthesis were reduced. Also, the delivery of glucan synthases to the
      cell surface, and the secretion of the Eng1p glucanase were defective. These
      results suggest that the defects in the cell wall observed in the conditional
      mutant were due to a defective secretion of enzymes involved in the
      synthesis/remodelling of this structure, rather than to their endocytosis. Our
      results show that a reduction in the amount of clathrin that has minor effects on
      general vesicle trafficking has a strong impact on cell wall synthesis, and
      suggest that this is the reason for the lethality of clc1Delta cells in the
      absence of osmotic stabilization. 

PMID- 23977062
TI  - Reliability of transcutaneous measurement of renal function in various strains of
      conscious mice.
AB  - Measuring renal function in laboratory animals using blood and/or urine sampling
      is not only labor-intensive but puts also a strain on the animal. Several
      approaches for fluorescence based transcutaneous measurement of the glomerular
      filtration rate (GFR) in laboratory animals have been developed. They allow the
      measurement of GFR based on the elimination kinetics of fluorescent exogenous
      markers. None of the studies dealt with the reproducibility of the measurements
      in the same animals. Therefore, the reproducibility of a transcutaneous GFR
      assessment method was investigated using the fluorescent renal marker FITC
      Sinistrin in conscious mice in the present study. We performed two transcutaneous
      GFR measurements within three days in five groups of mice (Balb/c, C57BL/6,
      SV129, NMRI at 3-4 months of age, and a group of 24 months old C57BL/6). Data
      were evaluated regarding day-to-day reproducibility as well as intra- and inter
      strain variability of GFR and the impact of age on these parameters. No
      significant differences between the two subsequent GFR measurements were
      detected. Fastest elimination for FITC-Sinistrin was detected in Balb/c with
      significant differences to C57BL/6 and SV129 mice. GFR decreased significantly
      with age in C57BL/6 mice. Evaluation of GFR in cohorts of young and old C57BL/6
      mice from the same supplier showed high consistency of GFR values between groups.
      Our study shows that the investigated technique is a highly reproducible and
      reliable method for repeated GFR measurements in conscious mice. This gentle
      method is easily used even in old mice and can be used to monitor the age-related
      decline in GFR. 

PMID- 23977063
TI  - Normalizing electrocardiograms of both healthy persons and cardiovascular disease
      patients for biometric authentication.
AB  - Although electrocardiogram (ECG) fluctuates over time and physical activity, some
      of its intrinsic measurements serve well as biometric features. Considering its
      constant availability and difficulty in being faked, the ECG signal is becoming a
      promising factor for biometric authentication. The majority of the currently
      available algorithms only work well on healthy participants. A novel
      normalization and interpolation algorithm is proposed to convert an ECG signal
      into multiple template cycles, which are comparable between any two ECGs, no
      matter the sampling rates or health status. The overall accuracies reach 100% and
      90.11% for healthy participants and cardiovascular disease (CVD) patients,
      respectively. 

PMID- 23977064
TI  - Ets2 in tumor fibroblasts promotes angiogenesis in breast cancer.
AB  - Tumor fibroblasts are active partners in tumor progression, but the genes and
      pathways that mediate this collaboration are ill-defined. Previous work
      demonstrates that Ets2 function in stromal cells significantly contributes to
      breast tumor progression. Conditional mouse models were used to study the
      function of Ets2 in both mammary stromal fibroblasts and epithelial cells.
      Conditional inactivation of Ets2 in stromal fibroblasts in PyMT and ErbB2 driven
      tumors significantly reduced tumor growth, however deletion of Ets2 in epithelial
      cells in the PyMT model had no significant effect. Analysis of gene expression in
      fibroblasts revealed a tumor- and Ets2-dependent gene signature that was enriched
      in genes important for ECM remodeling, cell migration, and angiogenesis in both
      PyMT and ErbB2 driven-tumors. Consistent with these results, PyMT and ErbB2
      tumors lacking Ets2 in fibroblasts had fewer functional blood vessels, and Ets2
      in fibroblasts elicited changes in gene expression in tumor endothelial cells
      consistent with this phenotype. An in vivo angiogenesis assay revealed the
      ability of Ets2 in fibroblasts to promote blood vessel formation in the absence
      of tumor cells. Importantly, the Ets2-dependent gene expression signatures from
      both mouse models were able to distinguish human breast tumor stroma from normal
      stroma, and correlated with patient outcomes in two whole tumor breast cancer
      data sets. The data reveals a key function for Ets2 in tumor fibroblasts in
      signaling to endothelial cells to promote tumor angiogenesis. The results
      highlight the collaborative networks that orchestrate communication between
      stromal cells and tumor cells, and suggest that targeting tumor fibroblasts may
      be an effective strategy for developing novel anti-angiogenic therapies. 

PMID- 23977065
TI  - Heterosubtypic antiviral activity of hemagglutinin-specific antibodies induced by
      intranasal immunization with inactivated influenza viruses in mice.
AB  - Influenza A virus subtypes are classified on the basis of the antigenicity of
      their envelope glycoproteins, hemagglutinin (HA; H1-H17) and neuraminidase. Since
      HA-specific neutralizing antibodies are predominantly specific for a single HA
      subtype, the contribution of antibodies to the heterosubtypic immunity is not
      fully understood. In this study, mice were immunized intranasally or
      subcutaneously with viruses having the H1, H3, H5, H7, H9, or H13 HA subtype, and
      cross-reactivities of induced IgG and IgA antibodies to recombinant HAs of the H1
      H16 subtypes were analyzed. We found that both subcutaneous and intranasal
      immunizations induced antibody responses to multiple HAs of different subtypes,
      whereas IgA was not detected remarkably in mice immunized subcutaneously. Using
      serum, nasal wash, and trachea-lung wash samples of H9 virus-immunized mice,
      neutralizing activities of cross-reactive antibodies were then evaluated by
      plaque-reduction assays. As expected, no heterosubtypic neutralizing activity was
      detected by a standard neutralization test in which viruses were mixed with
      antibodies prior to inoculation into cultured cells. Interestingly, however, a
      remarkable reduction of plaque formation and extracellular release of the H12
      virus, which was bound by the H9-induced cross-reactive antibodies, was observed
      when infected cells were subsequently cultured with the samples containing HA
      specific cross-reactive IgA. This heterosubtypic plaque reduction was interfered
      when the samples were pretreated with anti-mouse IgA polyclonal serum. These
      results suggest that the majority of HA-specific cross-reactive IgG and IgA
      antibodies produced by immunization do not block cellular entry of viruses, but
      cross-reactive IgA may have the potential to inhibit viral egress from infected
      cells and thus to play a role in heterosubtypic immunity against influenza A
      viruses. 

PMID- 23977066
TI  - Differential regulation of cysteinyl leukotriene receptor signaling by protein
      kinase C in human mast cells.
AB  - Cysteinyl leukotrienes (cys-LTs) are a group of lipid mediators that are potent
      bronchoconstrictors, powerful inducers of vascular leakage and potentiators of
      airway hyperresponsiveness. Cys-LTs play an essential role in asthma and are
      synthesized as well as activated in mast cells (MCs). Cys-LTs relay their effects
      mainly through two known GPCRs, CysLT1R and CysLT2R. Although protein kinase C
      (PKC) isoforms are implicated in the regulation of CysLT1R function, neither the
      role of PKCs in cys-LT-dependent MC inflammatory signaling nor the involvement of
      specific isoforms in MC function are known. Here, we show that PKC inhibition
      augmented LTD4 and LTE4-induced calcium influx through CysLT1R in MCs. In
      contrast, inhibition of PKCs suppressed c-fos expression as well MIP1beta
      generation by cys-LTs. Interestingly, cys-LTs activated both PKCalpha and
      PKCepsilon isoforms in MC. However, knockdown of PKCalpha augmented cys-LT
      mediated calcium flux, while knockdown of PKCepsilon attenuated cys-LT induced c
      fos expression and MIP1beta generation. Taken together, these results demonstrate
      for the first time that cys-LT signaling downstream of CysLT1R in MCs is
      differentially regulated by two distinct PKCs which modulate inflammatory signals
      that have significant pathobiologic implications in allergic reactions and asthma
      pathology. 

PMID- 23977067
TI  - Network topology reveals key cardiovascular disease genes.
AB  - The structure of protein-protein interaction (PPI) networks has already been
      successfully used as a source of new biological information. Even though
      cardiovascular diseases (CVDs) are a major global cause of death, many CVD genes
      still await discovery. We explore ways to utilize the structure of the human PPI
      network to find important genes for CVDs that should be targeted by drugs. The
      hope is to use the properties of such important genes to predict new ones, which
      would in turn improve a choice of therapy. We propose a methodology that examines
      the PPI network wiring around genes involved in CVDs. We use the methodology to
      identify a subset of CVD-related genes that are statistically significantly
      enriched in drug targets and "driver genes." We seek such genes, since driver
      genes have been proposed to drive onset and progression of a disease. Our
      identified subset of CVD genes has a large overlap with the Core Diseasome, which
      has been postulated to be the key to disease formation and hence should be the
      primary object of therapeutic intervention. This indicates that our methodology
      identifies "key" genes responsible for CVDs. Thus, we use it to predict new CVD
      genes and we validate over 70% of our predictions in the literature. Finally, we
      show that our predicted genes are functionally similar to currently known CVD
      drug targets, which confirms a potential utility of our methodology towards
      improving therapy for CVDs. 

PMID- 23977068
TI  - Sexually dimorphic genome-wide binding of retinoid X receptor alpha (RXRalpha)
      determines male-female differences in the expression of hepatic lipid processing
      genes in mice.
AB  - Many hepatic functions including lipid metabolism, drug metabolism, and
      inflammatory responses are regulated in a sex-specific manner due to distinct
      patterns of hepatic gene expression between males and females. Regulation for the
      majority of these genes is under control of Nuclear Receptors (NRs). Retinoid X
      Receptor alpha (RXRalpha) is an obligate partner for multiple NRs and considered
      a master regulator of hepatic gene expression, yet the full extent of RXRalpha
      chromatin binding in male and female livers is unclear. ChIP-Seq analysis of
      RXRalpha and RNA Polymerase2 (Pol2) binding was performed livers of both genders
      and combined with microarray analysis. Mice were gavage-fed with the RXR ligand
      LG268 for 5 days (30 mg/kg/day) and RXRalpha-binding and RNA levels were
      determined by ChIP-qPCR and qPCR, respectively. ChIP-Seq revealed 47,845 (male)
      and 46,877 (female) RXRalpha binding sites (BS), associated with ~12,700 unique
      genes in livers of both genders, with 91% shared between sexes. RXRalpha-binding
      showed significant enrichment for 2227 and 1498 unique genes in male and female
      livers, respectively. Correlating RXRalpha binding strength with Pol2-binding
      revealed 44 genes being male-dominant and 43 female-dominant, many previously
      unknown to be sexually-dimorphic. Surprisingly, genes fundamental to lipid
      metabolism, including Scd1, Fasn, Elovl6, and Pnpla3-implicated in Fatty Liver
      Disease pathogenesis, were predominant in females. RXRalpha activation using
      LG268 confirmed RXRalpha-binding was 2-3 fold increased in female livers at
      multiple newly identified RXRalpha BS including for Pnpla3 and Elovl6, with
      corresponding ~10-fold and ~2-fold increases in Pnpla3 and Elovl6 RNA
      respectively in LG268-treated female livers, supporting a role for RXRalpha
      regulation of sexually-dimorphic responses for these genes. RXRalpha appears to
      be one of the most widely distributed transcriptional regulators in mouse liver
      and is engaged in determining sexually-dimorphic expression of key lipid
      processing genes, suggesting novel gender- and gene-specific responses to NR
      based treatments for lipid-related liver diseases. 

PMID- 23977069
TI  - Preserving neural function under extreme scaling.
AB  - Important brain functions need to be conserved throughout organisms of extremely
      varying sizes. Here we study the scaling properties of an essential component of
      computation in the brain: the single neuron. We compare morphology and signal
      propagation of a uniquely identifiable interneuron, the HS cell, in the blowfly
      (Calliphora) with its exact counterpart in the fruit fly (Drosophila) which is
      about four times smaller in each dimension. Anatomical features of the HS cell
      scale isometrically and minimise wiring costs but, by themselves, do not scale to
      preserve the electrotonic behaviour. However, the membrane properties are set to
      conserve dendritic as well as axonal delays and attenuation as well as dendritic
      integration of visual information. In conclusion, the electrotonic structure of a
      neuron, the HS cell in this case, is surprisingly stable over a wide range of
      morphological scales. 

PMID- 23977070
TI  - Nitric oxide mediates root K+/Na+ balance in a mangrove plant, Kandelia obovata,
      by enhancing the expression of AKT1-type K+ channel and Na+/H+ antiporter under
      high salinity.
AB  - It is well known that nitric oxide (NO) enhances salt tolerance of glycophytes.
      However, the effect of NO on modulating ionic balance in halophytes is not very
      clear. This study focuses on the role of NO in mediating K(+)/Na(+) balance in a
      mangrove species, Kandelia obovata Sheue, Liu and Yong. We first analyzed the
      effects of sodium nitroprusside (SNP), an NO donor, on ion content and ion flux
      in the roots of K. obovata under high salinity. The results showed that 100 MUM
      SNP significantly increased K(+) content and Na(+) efflux, but decreased Na(+)
      content and K(+) efflux. These effects of NO were reversed by specific NO
      synthesis inhibitor and scavenger, which confirmed the role of NO in retaining
      K(+) and reducing Na(+) in K. obovata roots. Using western-blot analysis, we
      found that NO increased the protein expression of plasma membrane (PM) H(+)
      ATPase and vacuolar Na(+)/H(+) antiporter, which were crucial proteins for ionic
      balance. To further clarify the molecular mechanism of NO-modulated K(+)/Na(+)
      balance, partial cDNA fragments of inward-rectifying K(+) channel, PM Na(+)/H(+)
      antiporter, PM H(+)-ATPase, vacuolar Na(+)/H(+) antiporter and vacuolar H(+)
      ATPase subunit c were isolated. Results of quantitative real-time PCR showed that
      NO increased the relative expression levels of these genes, while this increase
      was blocked by NO synthesis inhibitors and scavenger. Above results indicate that
      NO greatly contribute to K(+)/Na(+) balance in high salinity-treated K. obovata
      roots, by activating AKT1-type K(+) channel and Na(+)/H(+) antiporter, which are
      the critical components in K(+)/Na(+) transport system. 

PMID- 23977071
TI  - Implant evaluation of an insertable cardiac monitor outside the electrophysiology
      lab setting.
AB  - BACKGROUND: To date, insertable cardiac monitors (ICM) have been implanted in the
      hospital without critical evaluation of other potential settings. Providing
      alternatives to in-hospital insertion may increase access to ICM, decrease
      waiting times for patients awaiting diagnosis, and reduce hospital resources.
      METHODS: This was a prospective, non-randomized, clinical trial involving nine
      clinical sites throughout the United States designed to assess the feasibility of
      ICM implants in a non-hospital setting. Other than the Reveal(r) ICM, implant
      supplies and techniques were left to physician discretion in patients who met
      indications. Patients were followed up to 90 days post-implant. The primary
      objective was to characterize the number of procedure-related adverse events that
      required surgical intervention within 90 days. RESULTS: Sixty-five patients were
      implanted at nine out-of-hospital sites. The insertion procedure was well
      tolerated by all patients. There were no deaths, systemic infections or
      endocarditis. There were two (3%) procedure-related adverse events requiring
      device explant and four (6%) adverse events not requiring explant. ICM use led to
      16 diagnoses (24.6%) with 9 patients proceeding to alternate cardiac device
      implants during the course of the 90-day follow up. CONCLUSION: Out-of-hospital
      ICM insertion can be accomplished with comparable procedural safety and
      represents a reasonable alternative to the in-hospital setting.
      CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01168427.

PMID- 23977072
TI  - Tacrolimus decreases albuminuria in patients with IgA nephropathy and normal
      blood pressure: a double-blind randomized controlled trial of efficacy of
      tacrolimus on IgA nephropathy.
AB  - BACKGROUND: Treatment remains uncertain for IgA nephropathy patients with mild to
      moderate proteinuria, for whom anti-hypertensive medication or the RAS blocker is
      not applicable due to low blood pressure. TRIAL DESIGN: A double blinded
      randomized trial. METHODS: The anti-proteinuric effect of tacrolimus was explored
      for 40 biopsy-proven mild IgA nephropathies for 16 weeks. We randomly assigned
      patients either to receive tacrolimus or placebo with stratification by using a
      renin angiotensin system blocker. The primary outcome was the percentage change
      of final UACR compared to the baseline value (pcUACR). RESULTS: The mean value of
      pcUACR at 12-week and 16-week visits (primary outcome) was decreased more in the
      Tac group compared to the control group (-52.0+/-26.4 vs -17.3+/-29.3%, p =
      0.001). At each visit, pcUACR was also decreased more in the Tac group compared
      to the control group. In the Tac group, the pcUACRs were -60.2+/-28.2%, -62.2+/
      33.9%, -48.5+/-29.8%, and -55.5+/-24.0%, and, in the control group, -6.8+/-32.2%,
      -2.5+/-35.9%, -12.7+/-34.2%, and -21.9+/-30.6%, at 4-week, 8-week, 12-week, and
      16-week visits, respectively. The pre-defined secondary outcomes were better in
      the Tac group compared to the control group. The frequency of decrease in pcUACR
      and percentage change of UPCR (pcUPCR) >=50% at 16 weeks were 65.0% (13/20) and
      55.0% (11/20)in the Tac group, and 25.0% (5/20) and 15.0% (3/20), in the control
      group, respectively (p = 0.025 for pcUACR and p = 0.019 for pcUPCR). However,
      tacrolimus wasn't effective with a dose of 0.05 mg/kg/day in patients taking ARB.
      The adverse events were tolerable. CONCLUSION: Tacrolimus effectively reduced
      proteinuria in IgA nephropathy with normal blood pressure. This suggested that
      tacrolimus could be an alternative to corticosteroid and RAS blocker for IgA
      nephropathy patients who cannot endure anti-hypertensive medication. TRIAL
      REGISTRATION: Clinicaltrial.gov NCT1224028.

PMID- 23977073
TI  - Sexual healthcare preferences among gay and bisexual men: a qualitative study in
      San Francisco, California.
AB  - BACKGROUND: Research on gay and other men who have sex with men's (G/MSM)
      preferences for sexual healthcare services focuses largely on HIV testing and to
      some extent on sexually transmitted infections (STI). This research illustrates
      the frequency and location of where G/MSM interface with the healthcare system,
      but it does not speak to why men seek care in those locations. As HIV and STI
      prevention strategies evolve, evidence about G/MSM's motivations and decision
      making can inform future plans to optimize models of HIV/STI prevention and
      primary care. METHODS: We conducted a phenomenological study of gay men's sexual
      health seeking experiences, which included 32 in-depth interviews with gay and
      bisexual men. Interviews were transcribed verbatim and entered into Atlas.ti. We
      conducted a Framework Analysis. FINDINGS: We identified a continuum of sexual
      healthcare seeking practices and their associated drivers. Men differed in their
      preferences for separating sexual healthcare from other forms of healthcare
      ("fragmentation") versus combining all care into one location ("consolidation").
      Fragmentation drivers included: fear of being monitored by insurance companies, a
      desire to seek non-judgmental providers with expertise in sexual health, a desire
      for rapid HIV testing, perceiving sexual health services as more convenient than
      primary care services, and a lack of healthcare coverage. Consolidation drivers
      included: a comfortable and trusting relationship with a provider, a desire for
      one provider to oversee overall health and those with access to public or private
      health insurance. CONCLUSIONS: Men in this study were likely to separate sexual
      healthcare from primary care. Based on this finding, we recommend placing new
      combination HIV/STI prevention interventions within sexual health clinics.
      Furthermore, given the evolution of the financing and delivery of healthcare
      services and in HIV prevention, policymakers and clinicians should consider
      including more primary care services within sexual healthcare settings.

PMID- 23977074
TI  - A chemically defined medium for rabbit embryo cryopreservation.
AB  - This study evaluates a new synthetic substitute (CRYO3, Ref. 5617, Stem Alpha,
      France) for animal-based products in rabbit embryo cryopreservation solutions.
      This evaluation was performed using two approaches: a thermodynamic approach
      using differential scanning calorimetry and a biological approach using rabbit
      embryo slow-freezing. During the experiment, foetal calf serum (FCS) was used as
      a reference. Because FCS varies widely by supplier, three different FCS were
      selected for the thermodynamic approach. The rabbit embryo slow-freezing
      solutions were made from Dulbecco's phosphate buffer saline containing 1.5 M
      Dimethyl Sulfoxide and 18% (v.v(-1)) of CRYO3 or 18% (v.v(-1)) of FCS. These
      solutions were evaluated using four characteristics: the end of melting
      temperature, the enthalpy of crystallisation (thermodynamic approach) and the
      embryo survival rates after culture and embryo transfer (biological approach). In
      the thermodynamic approach, the solutions containing one of the three different
      FCS had similar mean thermodynamic characteristics but had different
      variabilities in the overall data with aberrant values. The solution containing
      CRYO3 had similar thermodynamic properties when compared to those containing FCS.
      Moreover, no aberrant value was measured in the solution containing CRYO3. This
      solution appears to be more stable than the solutions containing a FCS. In the
      biological approach, the in vitro embryo survival rates obtained with the
      solution containing CRYO3 (73.7% and 81.3%) and with the solution containing a
      FCS (77.6% and 71.9%) were similar (p = 0.7). Nevertheless, during the in vivo
      evaluation, the implantation rate (21.8%) and the live-foetuses rate (18.8%) of
      the CRYO3 group were significantly higher than the implantation rate (7.1%, p =
      0.0002) and the live-foetuses rate (5.3%, p = 0.0002) of the FCS group. The
      pregnancy rate was also higher in the CRYO3 group compared to the FCS group
      (81.3% and 43.8%, respectively, p = 0.066). We conclude that CRYO3 can be used as
      a chemically defined substitute for animal-based products in rabbit embryo
      cryopreservation solutions. 

PMID- 23977075
TI  - Infant feeding and school attainment in five cohorts from low- and middle-income
      countries.
AB  - BACKGROUND: Performance in intelligence tests tends to be higher among
      individuals breastfed as infants, but little is known about the association
      between breastfeeding and achieved schooling. We assessed the association of
      infant feeding with school achievement in five cohorts from low- and middle
      income countries. Unlike high-income country settings where most previous studies
      come from, breastfeeding is not positively associated with socioeconomic position
      in our cohorts, thus reducing the likelihood of a spurious positive association.
      METHODOLOGY AND PRINCIPAL FINDINGS: Participants included 10,082 young adults
      from five birth cohorts (Brazil, India, Guatemala, the Philippines, and South
      Africa). The exposures variables were whether the subject was ever breastfed,
      total duration of breastfeeding, and age at introduction of complementary foods.
      We adjusted the estimates for age at follow up, sex, maternal age, smoking during
      pregnancy, birthweight and socioeconomic position at birth. The key outcome was
      the highest grade achieved at school. In unadjusted analyses, the association
      between ever breastfeeding and schooling was positive in Brazil, inverse in the
      Philippines, and null in South Africa; in adjusted analyses, these associations
      were attenuated. In Brazil, schooling was highest among individuals breastfed for
      3-12 months whereas in the Philippines duration of breastfeeding was inversely
      associated with schooling; and null associations were observed in South Africa
      and Guatemala. These associations were attenuated in adjusted models. Late
      introduction of solid foods was associated with lower schooling achievement in
      Brazil and South Africa. CONCLUSION: Measures of breastfeeding are not
      consistently related to schooling achievement in contemporary cohorts of young
      adults in lower and middle-income countries.

PMID- 23977076
TI  - Induction of encephalitis in rhesus monkeys infused with lymphocryptovirus
      infected B-cells presenting MOG(34-56) peptide.
AB  - The overlapping epidemiology of multiple sclerosis (MS) and Epstein-Barr virus
      (EBV), the increased risk to develop MS after infectious mononucleosis (IM) and
      the localization of EBV-infected B-cells within the MS brain suggest a causal
      link between EBV and MS. However, the underlying mechanism is unknown. We
      hypothesize that EBV-infected B-cells are capable of eliciting a central nervous
      system (CNS) targeting autoimmune reaction. To test this hypothesis we have
      developed a novel experimental model in rhesus monkeys of IM-like disease induced
      by infusing autologous B-lymphoblastoid cells (B-LCL). Herpesvirus papio (HVP) is
      a lymphocryptovirus related to EBV and was used to generate rhesus monkey B-LCL.
      Three groups of five animals were included; each group received three intravenous
      infusions of B-LCL that were either pulsed with the encephalitogenic self peptide
      MOG(34-56) (group A), a mimicry peptide (981-1003) of the major capsid protein of
      cytomegalovirus (CMVmcp(981-1003); group B) or the citrullinated MOG(34-56)
      (cMOG(34-56); group C). Groups A and B received on day 98 a single immunization
      with MOG(34-56) in incomplete Freund's adjuvant (IFA). Group C monkeys were
      euthanized just prior to day 98 without booster immunization. We observed self
      peptide-specific proliferation of T-cells, superimposed on similar strong
      proliferation of CD3(+)CD8(+) T-cells against the B-LCL as observed in IM. The
      brains of several monkeys contained perivascular inflammatory lesions of variable
      size, comprising CD3(+) and CD68(+) cells. Moreover, clusters of CD3(+) and
      CD20(+) cells were detected in the meninges. The only evident clinical sign was
      substantial loss of bodyweight (>15%), a symptom observed both in early
      autoimmune encephalitis and IM. In conclusion, this model suggests that EBV
      induced B-LCL can elicit a CNS targeting inflammatory (auto)immune reaction.

PMID- 23977077
TI  - Leflunomide reduces proliferation and induces apoptosis in neuroblastoma cells in
      vitro and in vivo.
AB  - Leflunomide as an immunosuppressive drug is generally used in the treatment of
      rheumatoid arthritis. It inhibits DHODH (dihydroorotate dehydrogenase ), which is
      one of the essential enzymes in the de novo pyrimidine biosynthetic pathway. Here
      we showed that leflunomide significantly reduced cell proliferation and self
      renewal activity. Annexin V-FITC/PI staining assay revealed that leflunomide
      induced S-phase cell cycle arrest, and promoted cell apoptosis. In vivo xenograft
      study in SCID mice showed that leflunomide inhibited tumor growth and
      development. We also observed that DHODH was commonly expressed in neuroblastoma.
      When treated with leflunomide, the neuroblastoma cell lines BE(2)-C, SK-N-DZ, and
      SK-N-F1 showed dramatic inhibition of DHODH at mRNA and protein levels.
      Considering the favorable toxicity profile and the successful clinical experience
      with leflunomide in rheumatoid arthritis, this drug represents a potential new
      candidate for targeted therapy in neuroblastoma. 

PMID- 23977078
TI  - Seven-year surveillance of emm types of pediatric Group A streptococcal
      pharyngitis isolates in Western Greece.
AB  - BACKGROUND: An experimental 26-valent M protein Group A streptococcal (GAS)
      vaccine has entered clinical studies. Pharyngeal GAS emm type surveillances in
      different areas and time-periods enhance the understanding of the epidemiology of
      GAS pharyngitis. Moreover, these surveillances, combined with the data on GAS
      invasive disease, can play a significant role in the formulation of multivalent
      type-specific vaccines. METHODS: During a 7-year period (1999-2005), 2408 GAS
      isolates were recovered from consecutive children with pharyngitis in Western
      Greece. The overall macrolide resistance rate was 22.8%. Along the study period
      we noted a tendency towards significantly decreased rates of resistance, with the
      lowest rates occurring in 2002 (15.3%), 2003 (15%) and 2004 (16.7%). A random
      sample of isolates from each year, 338 (61.7%) of the 548 macrolide-resistant and
      205 (11%) of the macrolide-susceptible, underwent molecular analysis, including
      emm typing. RESULTS: The 543 typed isolates had 28 different emm types. A
      statistically significant association was found between macrolide resistance and
      emm4, emm22 and emm77, whereas emm1, emm3, emm6, emm12, emm87 and emm89 were
      associated with macrolide susceptibility. A significant yearly fluctuation was
      observed in emm4, emm28 and emm77. The most common macrolide-resistant GAS were
      emm77 isolates harboring erm(A), either alone or in combination with mef(A), emm4
      carrying mef(A), emm28 possessing erm(B), emm75 carrying mef(A), emm12 harboring
      mef(A) and emm22 carrying erm(A). We estimated that 82.8% of the isolates
      belonged to emm types included in the novel 26-valent M protein vaccine. The
      vaccine coverage rate was determined mainly by the increased frequency of
      nonvaccine emm4 isolates. CONCLUSIONS: A limited number of emm types dominated
      among macrolide-susceptible and macrolide-resistant GAS isolates. We observed
      seasonal fluctuations, which were significant for emm4, emm28 and emm77. This
      type of data can serve as baseline information if the novel 26-valent M protein
      GAS vaccine is introduced into practice.

PMID- 23977079
TI  - Diversity of Aplochiton fishes (Galaxiidea) and the taxonomic resurrection of A.
      marinus.
AB  - Aplochiton is a small genus of galaxiid fishes endemic to Patagonia and the
      Falkland Islands whose taxonomy is insufficiently resolved. Recent genetic
      analyses confirmed the existence of only two closely related species, Aplochiton
      taeniatus and Aplochiton zebra, while a third controversial species, Aplochiton
      marinus, remained lost to synonymy with A. taeniatus. Using an integrative
      taxonomy framework, we studied original samples and published sequences from a
      broad range in western Patagonia and the Falkland Islands, and generated robust
      species hypotheses based on single-locus (Cytochrome Oxidase subunit I; COI)
      species-delineation methods and known diagnostic morphological characters
      analyzed in a multivariate context. Results revealed three distinct evolutionary
      lineages that morphologically resemble, in important respects, existing nominal
      species descriptions. Interestingly, the lineage associated with A. marinus was
      unambiguously identifiable (100% accuracy) both from the genetic and
      morphological viewpoints. In contrast, the morphology of A. taeniatus and A.
      zebra overlapped substantially, mainly due to the high variability of A.
      taeniatus. Discriminant function analysis aided the identification of these
      species with 83.9% accuracy. Hence, for their unambiguous identification, genetic
      screening is needed. A. marinus has seldom been documented, and when recorded, it
      has always been found in sites with clear marine influence. It is possible that
      only A. marinus preserves a life cycle related to the sea akin to the
      hypothesized ancestral galaxiid. We did not find evidence of claimed diadromy in
      A. taeniatus or A. zebra, and, therefore, these should be regarded as freshwater
      species. Finally, a lack of phylogeographic patterns and overrepresentation of
      uncommon haplotypes suggested demographic expansions in recent evolutionary time,
      especially of A. zebra, in line with the hypothesis of large-scale range
      expansion and lineage spread in western Patagonia. 

PMID- 23977080
TI  - Carboxypeptidase E/NFalpha1: a new neurotrophic factor against oxidative stress
      induced apoptotic cell death mediated by ERK and PI3-K/AKT pathways.
AB  - Mice lacking Carboxypeptidase E (CPE) exhibit degeneration of hippocampal neurons
      caused by stress at weaning while over-expression of CPE in hippocampal neurons
      protect them against hydrogen peroxide-induced cell death. Here we demonstrate
      that CPE acts as an extracellular trophic factor to protect neurons. Rat
      hippocampal neurons pretreated with purified CPE protected the cells against
      hydrogen peroxide-, staurosporine- and glutamate-induced cell death. This
      protection was observed even when hippocampal neurons were treated with an
      enzymatically inactive mutant CPE or with CPE in the presence of its inhibitor,
      GEMSA. Purified CPE added to the culture medium rescued CPE knock-out hippocampal
      neurons from cell death. Both ERK and AKT were phosphorylated within 15 min after
      CPE treatment of hippocampal neurons and, using specific inhibitors, both
      signaling pathways were shown to be required for the neuroprotective effect. The
      expression of the anti-apoptotic protein, B-cell lymphoma 2 (BCL-2), was up
      regulated after hippocampal neurons were treated with CPE. Furthermore, hydrogen
      peroxide induced down-regulation of BCL-2 protein and subsequent activation of
      caspase-3 were inhibited by CPE treatment. Thus, this study has identified CPE as
      a new neurotrophic factor that can protect neurons against degeneration through
      the activation of ERK and AKT signaling pathways to up-regulate expression of BCL
      2. 

PMID- 23977081
TI  - PARP-1 controls immunosuppressive function of regulatory T cells by destabilizing
      Foxp3.
AB  - Poly (ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme and transcription
      factor that is involved in inflammatory response, but its role in T cell response
      remains largely unknown. We show here that PARP-1 regulates the suppressive
      function of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs). Specifically, Tregs
      in mice with a null mutation of the PARP-1 gene (PARP-1(-/-)) showed
      significantly stronger suppressive activity than did wild-type Tregs in culture.
      We elucidate that this enhanced suppressive function is attributed to sustained
      higher expression of Foxp3 and CD25 in PARP-1(-/-) Tregs. Furthermore, in PARP-1(
      /-) Tregs, Foxp3 protein shows substantially higher levels of binding to the
      conserved non-coding DNA sequence 2 (CNS2) at the foxp3 gene, a region important
      in maintaining Foxp3 gene expression in Tregs. Thus, our data reveal a role for
      PARP-1 in controlling the function of Tregs through modulation of the stable
      expression of Foxp3. 

PMID- 23977082
TI  - Metagenomic analysis of the ferret fecal viral flora.
AB  - Ferrets are widely used as a small animal model for a number of viral infections,
      including influenza A virus and SARS coronavirus. To further analyze the
      microbiological status of ferrets, their fecal viral flora was studied using a
      metagenomics approach. Novel viruses from the families Picorna-, Papilloma-, and
      Anelloviridae as well as known viruses from the families Astro-, Corona-, Parvo-,
      and Hepeviridae were identified in different ferret cohorts. Ferret kobu- and
      hepatitis E virus were mainly present in human household ferrets, whereas
      coronaviruses were found both in household as well as farm ferrets. Our studies
      illuminate the viral diversity found in ferrets and provide tools to prescreen
      for newly identified viruses that potentially could influence disease outcome of
      experimental virus infections in ferrets. 

PMID- 23977083
TI  - High sensitivity of Giardia duodenalis to tetrahydrolipstatin (orlistat) in
      vitro.
AB  - Giardiasis, a gastrointestinal disease caused by Giardia duodenalis, is currently
      treated mainly with nitroimidazoles, primarily metronidazole (MTZ). Treatment
      failure rates of up to 20 percent reflect the compelling need for alternative
      treatment options. Here, we investigated whether orlistat, a drug approved to
      treat obesity, represents a potential therapeutic agent against giardiasis. We
      compared the growth inhibitory effects of orlistat and MTZ on a long-term in
      vitro culture adapted G. duodenalis strain, WB-C6, and on a new isolate, 14
      03/F7, from a patient refractory to MTZ treatment using a resazurin assay. The
      giardiacidal concentration of the drugs and their combined in vitro efficacy was
      determined by median-effect analysis. Morphological changes after treatment were
      analysed by light and electron microscopy. Orlistat inhibited the in vitro growth
      of G. duodenalis at low micromolar concentrations, with isolate 14-03/F7
      (IC50(24h) = 2.8 uM) being more sensitive than WB-C6 (IC50(24h) = 6.2 uM). The
      effect was significantly more potent compared to MTZ (IC50(24h) = 4.3 uM and 11.0
      uM, respectively) and led to specific undulated morphological alterations on the
      parasite surface. The giardiacidal concentration of orlistat was >14 uM for 14
      03/F7 and >43 uM for WB-C6, respectively. Importantly, the combination of both
      drugs revealed no interaction on their inhibitory effects. We demonstrate that
      orlistat is a potent inhibitor of G. duodenalis growth in vitro and kills
      parasites at concentrations achievable in the gut by approved treatment regimens
      for obesity. We therefore propose to investigate orlistat in controlled clinical
      studies as a new drug in giardiasis.

PMID- 23977084
TI  - Priming with recombinant auxotrophic BCG expressing HIV-1 Gag, RT and Gp120 and
      boosting with recombinant MVA induces a robust T cell response in mice.
AB  - In previous studies we have shown that a pantothenate auxotroph of Myocbacterium
      bovis BCG (BCGDeltapanCD) expressing HIV-1 subtype C Gag induced Gag-specific
      immune responses in mice and Chacma baboons after prime-boost immunization in
      combination with matched rMVA and VLP vaccines respectively. In this study
      recombinant BCG (rBCG) expressing HIV-1 subtype C reverse transcriptase and a
      truncated envelope were constructed using both the wild type BCG Pasteur strain
      as a vector and the pantothenate auxotroph. Mice were primed with rBCG expressing
      Gag and RT and boosted with a recombinant MVA, expressing a polyprotein of Gag,
      RT, Tat and Nef (SAAVI MVA-C). Priming with rBCGDeltapanCD expressing Gag or RT
      rather than the wild type rBCG expressing Gag or RT resulted in higher
      frequencies of total HIV-specific CD8(+) T cells and increased numbers of T cells
      specific to the subdominant Gag and RT epitopes. Increasing the dose of rBCG from
      10(5) cfu to 10(7) cfu also led to an increase in the frequency of responses to
      subdominant HIV epitopes. A mix of the individual rBCGDeltapanCD vaccines
      expressing either Gag, RT or the truncated Env primed the immune system for a
      boost with SAAVI MVA-C and generated five-fold higher numbers of HIV-specific IFN
      gamma-spot forming cells than mice primed with rBCGDeltapanCD containing an empty
      vector control. Priming with the individual rBCGDeltapanCD vaccines or the mix
      and boosting with SAAVI MVA-C also resulted in the generation of HIV-specific
      CD4(+) and CD8(+) T cells producing IFN-gamma and TNF-alpha and CD4(+) cells
      producing IL-2. The rBCG vaccines tested in this study were able to prime the
      immune system for a boost with rMVA expressing matching antigens, inducing
      robust, HIV-specific T cell responses to both dominant and subdominant epitopes
      in the individual proteins when used as individual vaccines or in a mix. 

PMID- 23977086
TI  - N-terminal domain of turkey pancreatic lipase is active on long chain
      triacylglycerols and stabilized by colipase.
AB  - The gene encoding the TPL N-terminal domain (N-TPL), fused with a His6-tag, was
      cloned and expressed in Pichia pastoris, under the control of the glyceraldehyde
      3-phosphate dehydrogenase (GAP) constitutive promoter. The recombinant protein
      was successfully expressed and secreted with an expression level of 5 mg/l of
      culture medium after 2 days of culture. The N-TPL was purified through a one-step
      Ni-NTA affinity column with a purification factor of approximately 23-fold. The
      purified N-TPL, with a molecular mass of 35 kDa, had a specific activity of 70
      U/mg on tributyrin. Surprisingly, this domain was able to hydrolyse long chain TG
      with a specific activity of 11 U/mg using olive oil as substrate. This result was
      confirmed by TLC analysis showing that the N-TPL was able to hydrolyse insoluble
      substrates as olive oil. N-TPL was unstable at temperatures over 37 degrees C and
      lost 70% of its activity at acid pH, after 5 min of incubation. The N-TPL
      exhibited non linear kinetics, indicating its rapid denaturation at the
      tributyrin-water interface. Colipase increased the N-TPL stability at the lipid
      water interface, so the TPL N-terminal domain probably formed functional
      interactions with colipase despite the absence of the C-terminal domain. 

PMID- 23977085
TI  - Functional promoter -94 ins/del ATTG polymorphism in NFKB1 gene is associated
      with bladder cancer risk in a Chinese population.
AB  - BACKGROUND: A functional -94 insertion/deletion polymorphism (rs28362491) in the
      promoter of the NFKB1 gene was reported to influence NFKB1 expression and confer
      susceptibility to different types of cancer. This study aims to determine whether
      the polymorphism is associated with risk of bladder cancer. MATERIALS AND
      METHODS: TaqMan assay was used to determine genotype among 609 cases and 640
      controls in a Chinese population. Logistic regression was used to assess the
      association between the polymorphism and bladder cancer risk, and quantitative
      real-time polymerase chain reaction was used to determine NFKB1 mRNA expression.
      RESULTS: Compared with the ins/ins/ins/del genotypes, the del/del genotype was
      associated with a significantly increased risk of bladder cancer [adjusted odd
      ratio (OR) = 1.92, 95% confidence interval (CI) = 1.42-2.59]. The increased risk
      was more prominent among subjects over 65 years old (OR = 2.37, 95% CI= 1.52
      3.70), male subjects (OR = 1.97, 95% CI = 1.40-2.79) and subjects with self
      reported family history of cancer (OR = 3.59, 95% CI = 1.19-10.9). Furthermore,
      the polymorphism was associated with a higher risk of developing non-muscle
      invasive bladder cancer (OR= 2.07, 95% CI= 1.51-2.85), grade 1 bladder cancer (OR
      = 2.40, 95% CI = 1.68-3.43), single tumor bladder cancer (OR = 2.04, 95% CI =
      1.48-2.82) and smaller tumor size bladder cancer (OR = 2.10, 95% CI= 1.51-2.92).
      The expression of NFKB1 mRNA in bladder cancer tissues with homozygous insertion
      genotype was higher than that with deletion allele. CONCLUSIONS: In conclusion,
      the -94 ins/del ATTG polymorphism in NFKB1 promoter may contribute to the
      etiology of bladder cancer in the Chinese population.

PMID- 23977087
TI  - Computational and experimental validation of B and T-cell epitopes of the in vivo
      immune response to a novel malarial antigen.
AB  - Vaccine development efforts will be guided by algorithms that predict immunogenic
      epitopes. Such prediction methods rely on classification-based algorithms that
      are trained against curated data sets of known B and T cell epitopes. It is
      unclear whether this empirical approach can be applied prospectively to predict
      epitopes associated with protective immunity for novel antigens. We present a
      comprehensive comparison of in silico B and T cell epitope predictions with in
      vivo validation using an previously uncharacterized malaria antigen, CelTOS.
      CelTOS has no known conserved structural elements with any known proteins, and
      thus is not represented in any epitope databases used to train prediction
      algorithms. This analysis represents a blind assessment of this approach in the
      context of a novel, immunologically relevant antigen. The limited accuracy of the
      tested algorithms to predict the in vivo immune responses emphasizes the need to
      improve their predictive capabilities for use as tools in vaccine design. 

PMID- 23977088
TI  - Considerations for subgroups and phenocopies in complex disease genetics.
AB  - The number of identified genetic variants associated to complex disease cannot
      fully explain heritability. This may be partially due to more complicated
      patterns of predisposition than previously suspected. Diseases such as multiple
      sclerosis (MS) may consist of multiple disease causing mechanisms, each comprised
      of several elements. We describe how the effect of subgroups can be calculated
      using the standard association measurement odds ratio, which is then manipulated
      to provide a formula for the true underlying association present within the
      subgroup. This is sensitive to the initial minor allele frequencies present in
      both cases and the subgroup of patients. The methodology is then extended to the
      chi(2) statistic, for two related scenarios. First, to determine the true chi(2)
      when phenocopies or disease subtypes reduce association and are reclassified as
      controls when calculating statistics. Here, the chi(2) is given by (1 + sigma *
      (a + b)/(c + d))/(1 - sigma), or (1 + sigma)/(1 - sigma) for equal numbers of
      cases and controls. Second, when subgroups corresponding to heterogeneity mask
      the true effect size, but no reclassification is made. Here, the proportion
      increase in total sample size required to attain the same chi(2) statistic as the
      subgroup is given as gamma = (1 - sigma/2)/((1 - sigma)(1 - sigmac/(a + c))(1 -
      sigmad/(b + d))), and a python script to calculate and plot this value is
      provided at kirc.se. Practical examples show how in a study of modest size (1000
      cases and 1000 controls), a non-significant SNP may exceed genome-wide
      significance when corresponding to a subgroup of 20% of cases, and may occur in
      heterozygous form in all cases. This methodology may explain the modest
      association found in diseases such as MS wherein heterogeneity confounds
      straightforward measurement of association.

PMID- 23977089
TI  - Rotavirus seasonality and age effects in a birth cohort study of southern India.
AB  - INTRODUCTION: Understanding the temporal patterns in disease occurrence is
      valuable for formulating effective disease preventive programs. Cohort studies
      present a unique opportunity to explore complex interactions associated with
      emergence of seasonal patterns of infectious diseases. METHODS: We used data from
      452 children participating in a birth cohort study to assess the seasonal
      patterns of rotavirus diarrhea by creating a weekly time series of rotavirus
      incidence and fitting a Poisson harmonic regression with biannual peaks. Age and
      cohort effects were adjusted for by including the weekly counts of number of
      children in the study and the median age of cohort in a given week. Weekly
      average temperature, humidity and an interaction term to reflect the joint effect
      of temperature and humidity were included to consider the effects of
      meteorological variables. RESULTS: In the overall rotavirus time series, two
      significant peaks within a single year were observed--one in winter and the other
      in summer. The effect of age was found to be the most significant contributor for
      rotavirus incidence, showing a strong negative association. Seasonality remained
      a significant factor, even after adjusting for meteorological parameters, and the
      age and cohort effects. CONCLUSIONS: The methodology for assessing seasonality in
      cohort studies is not yet developed. This is the first attempt to explore
      seasonal patterns in a cohort study with a dynamic denominator and rapidly
      changing immune response on individual and group levels, and provides a highly
      promising approach for a better understanding of the seasonal patterns of
      infectious diseases, tracking emergence of pathogenic strains and evaluating the
      efficacy of intervention programs.

PMID- 23977090
TI  - Patterns of human papillomavirus types in multiple infections: an analysis in
      women and men of the high throughput human papillomavirus monitoring study.
AB  - BACKGROUND: To evaluate the pattern of co-infection of human papillomavirus (HPV)
      types in both sexes in Sweden. METHODS: Cell samples from genital swabs, first
      void urine, and genital swabs immersed in first-void urine were collected in the
      present cross-sectional High Throughput HPV Monitoring study. Overall, 31,717
      samples from women and 9,949 from men (mean age 25) were tested for 16 HPV types
      using mass spectrometry. Multilevel logistic regression was used to estimate the
      expected number of multiple infections with specific HPV types, adjusted for age,
      type of sample, and accounting for correlations between HPV types due to
      unobserved risk factors using sample-level random effects. Bonferroni correction
      was used to allow for multiple comparisons (120). RESULTS: Observed-to-expected
      ratio for any multiple infections was slightly above unity in both sexes, but,
      for most 2-type combinations, there was no evidence of significant departure from
      expected numbers. HPV6/18 was found more often and HPV51/68 and 6/68 less often
      than expected. However, HPV68 tended to be generally underrepresented in co
      infections, suggesting a sub-optimal performance of our testing method for this
      HPV type. CONCLUSIONS: We found no evidence for positive or negative clustering
      between HPV types included in the current prophylactic vaccines and other
      untargeted oncogenic types, in either sex.

PMID- 23977091
TI  - A genome-wide association study identifies risk loci to equine recurrent uveitis
      in German warmblood horses.
AB  - Equine recurrent uveitis (ERU) is a common eye disease affecting up to 3-15% of
      the horse population. A genome-wide association study (GWAS) using the Illumina
      equine SNP50 bead chip was performed to identify loci conferring risk to ERU. The
      sample included a total of 144 German warmblood horses. A GWAS showed a
      significant single nucleotide polymorphism (SNP) on horse chromosome (ECA) 20 at
      49.3 Mb, with IL-17A and IL-17F being the closest genes. This locus explained a
      fraction of 23% of the phenotypic variance for ERU. A GWAS taking into account
      the severity of ERU, revealed a SNP on ECA18 nearby to the crystalline gene
      cluster CRYGA-CRYGF. For both genomic regions on ECA18 and 20, significantly
      associated haplotypes containing the genome-wide significant SNPs could be
      demonstrated. In conclusion, our results are indicative for a genetic component
      regulating the possible critical role of IL-17A and IL-17F in the pathogenesis of
      ERU. The associated SNP on ECA18 may be indicative for cataract formation in the
      course of ERU. 

PMID- 23977092
TI  - Swiprosin-1 is a novel actin bundling protein that regulates cell spreading and
      migration.
AB  - Protein functions are often revealed by their localization to specialized
      cellular sites. Recent reports demonstrated that swiprosin-1 is found together
      with actin and actin-binding proteins in the cytoskeleton fraction of human mast
      cells and NK-like cells. However, direct evidence of whether swiprosin-1
      regulates actin dynamics is currently lacking. We found that swiprosin-1
      localizes to microvilli-like membrane protrusions and lamellipodia and exhibits
      actin-binding activity. Overexpression of swiprosin-1 enhanced lamellipodia
      formation and cell spreading. In contrast, swiprosin-1 knockdown showed reduced
      cell spreading and migration. Swiprosin-1 induced actin bundling in the presence
      of Ca(2+), and deletion of the EF-hand motifs partially reduced bundling
      activity. Swiprosin-1 dimerized in the presence of Ca(2+) via its coiled-coil
      domain, and a lysine (Lys)-rich region in the coiled-coil domain was essential
      for regulation of actin bundling. Consistent with these observations, mutations
      of the EF-hand motifs and coiled-coil region significantly reduced cell spreading
      and lamellipodia formation. We provide new evidence of how swiprosin-1 influences
      cytoskeleton reorganization and cell spreading. 

PMID- 23977093
TI  - Novel biomarkers of arterial and venous ischemia in microvascular flaps.
AB  - The field of reconstructive microsurgery is experiencing tremendous growth, as
      evidenced by recent advances in face and hand transplantation, lower limb salvage
      after trauma, and breast reconstruction. Common to all of these procedures is the
      creation of a nutrient vascular supply by microsurgical anastomosis between a
      single artery and vein. Complications related to occluded arterial inflow and
      obstructed venous outflow are not uncommon, and can result in irreversible tissue
      injury, necrosis, and flap loss. At times, these complications are challenging to
      clinically determine. Since early intervention with return to the operating room
      to re-establish arterial inflow or venous outflow is key to flap salvage, the
      accurate diagnosis of early stage complications is essential. To date, there are
      no biochemical markers or serum assays that can predict these complications. In
      this study, we utilized a rat model of flap ischemia in order to identify the
      transcriptional signatures of venous congestion and arterial ischemia. We found
      that the critical ischemia time for the superficial inferior epigastric
      fasciocutaneus flap was four hours and therefore performed detailed analyses at
      this time point. Histolgical analysis confirmed significant differences between
      arterial and venous ischemia. The transcriptome of ischemic, congested, and
      control flap tissues was deciphered by performing Affymetrix microarray analysis
      and verified by qRT-PCR. Principal component analysis revealed that arterial
      ischemia and venous congestion were characterized by distinct transcriptomes.
      Arterial ischemia and venous congestion was characterized by 408 and 1536>2-fold
      differentially expressed genes, respectively. qRT-PCR was used to identify five
      candidate genes Prol1, Muc1, Fcnb, Il1b, and Vcsa1 to serve as biomarkers for
      flap failure in both arterial ischemia and venous congestion. Our data suggests
      that Prol1 and Vcsa1 may be specific indicators of venous congestion and allow
      clinicians to both diagnose and successfully treat microvascular complications
      before irreversible tissue damage and flap loss occurs. 

PMID- 23977094
TI  - Down regulation of T cell receptor expression in COPD pulmonary CD8 cells.
AB  - CD8 cells may contribute towards an autoimmune process in COPD. Down regulation
      of T cell receptor (TCR) signalling molecules occurs in autoimmune diseases with
      consequent T cell dysfunction. We hypothesise that TCR signalling is abnormal in
      COPD pulmonary CD8 cells. Micro-array gene expression analysis of blood and
      pulmonary COPD CD8 samples was performed and compared to pulmonary CD8 cells from
      smoker controls (S). We focused on the TCR signalling pathway, with validation of
      key findings using polymerase chain reaction and immunofluorescence. TCR
      signalling molecules in COPD pulmonary CD8 cells were down regulated compared to
      blood CD8 cells (CD247: fold change (FC) -2.43, Q = 0.001; LCK: FC -2.25, Q =
      0.01). Micro-array analysis revealed no significant differences between COPD and
      S pulmonary CD8 cells. However, PCR revealed significantly lower gene expression
      levels of CD247 (FC -1.79, p = 0.04) and LCK (FC -1.77, p = 0.01) in COPD
      compared to S pulmonary CD8 cells. CD247 down regulation in COPD CD8 cells was
      confirmed by immunofluorescent staining of bronchoalveolar lavage cells:
      Significantly fewer COPD CD8 cells co-expressed CD247 compared to healthy non
      smoker CD8 cells (mean 88.9 vs 75.2%, p<0.05) There is down regulation of TCR
      signalling molecules in COPD pulmonary CD8 cells. This may cause T cell
      dysfunction. 

PMID- 23977096
TI  - Use of geospatial modeling to predict Schistosoma mansoni prevalence in Nyanza
      Province, Kenya.
AB  - BACKGROUND: Schistosomiasis, a parasitic disease that affects over 200 million
      people, can lead to significant morbidity and mortality; distribution of single
      dose preventative chemotherapy significantly reduces disease burden.
      Implementation of control programs is dictated by disease prevalence rates, which
      are determined by costly and labor intensive screening of stool samples. Because
      ecological and human factors are known to contribute to the focal distribution of
      schistosomiasis, we sought to determine if specific environmental and geographic
      factors could be used to accurately predict Schistosoma mansoni prevalence in
      Nyanza Province, Kenya. METHODOLOGY/PRINCIPAL FINDINGS: A spatial mixed model was
      fit to assess associations with S. mansoni prevalence in schools. Data on S.
      mansoni prevalence and GPS location of the school were obtained from 457 primary
      schools. Environmental and geographic data layers were obtained from publicly
      available sources. Spatial models were constructed using ArcGIS 10 and R 2.13.0.
      Lower S.mansoni prevalence was associated with further distance (km) to Lake
      Victoria, higher day land surface temperature (LST), and higher monthly rainfall
      totals. Altitude, night LST, human influence index, normalized difference
      vegetation index, soil pH, soil texture, soil bulk density, soil water capacity,
      population, and land use variables were not significantly associated with S.
      mansoni prevalence. CONCLUSIONS: Our model suggests that there are specific
      environmental and geographic factors that influence S. mansoni prevalence rates
      in Nyanza Province, Kenya. Validation and use of schistosomiasis prevalence maps
      will allow control programs to plan and prioritize efficient control campaigns to
      decrease schistosomiasis burden.

PMID- 23977095
TI  - Notch pathway activation contributes to inhibition of C2C12 myoblast
      differentiation by ethanol.
AB  - The loss of muscle mass in alcoholic myopathy may reflect alcohol inhibition of
      myogenic cell differentiation into myotubes. Here, using a high content imaging
      system we show that ethanol inhibits C2C12 myoblast differentiation by reducing
      myogenic fusion, creating smaller and less complex myotubes compared with
      controls. Ethanol administration during C2C12 differentiation reduced MyoD and
      myogenin expression, and microarray analysis identified ethanol activation of the
      Notch signaling pathway target genes Hes1 and Hey1. A reporter plasmid regulated
      by the Hes1 proximal promoter was activated by alcohol treatment in C2C12 cells.
      Treatment of differentiating C2C12 cells with a gamma secretase inhibitor (GSI)
      abrogated induction of Hes1. On a morphological level GSI treatment completely
      rescued myogenic fusion defects and partially restored other myotube parameters
      in response to alcohol. We conclude that alcohol inhibits C2C12 myoblast
      differentiation and the inhibition of myogenic fusion is mediated by Notch
      pathway activation. 

PMID- 23977097
TI  - High peritoneal KT/V and peritonitis rates are associated with peritoneal
      calcification.
AB  - BACKGROUND: Peritoneal calcification (PC) is a specific finding in patients
      undergoing peritoneal dialysis (PD), but its prevalence, risk factors, and
      impacts in PD patients remain unclear. The present study investigated these
      issues and provided information useful for the management of PC. METHODS: The
      study included 183 PD patients. The severity of PC was determined using abdominal
      computed tomography (CT), and we summed up all scores from slices obtained from
      the diaphragm to the pelvic floor normalized to body surface area. We analyzed
      the associations between PC and demographic and clinical characteristics, and
      between PC and levels of biomarkers, including C-reactive protein (CRP),
      osteoprotegrin and fetuin-A. The determinants of PC were examined using multiple
      regression analysis. RESULTS: Patients were categorized into group 1 (without PC,
      n = 133) and group 2 (with PC, n = 50). Group 2 patients showed different degrees
      of PC with a mean of 160+/-769 mm(2)/m(2). Group 1 patients had higher fetuin-A
      levels than group 2 patients (861+/-309 vs. 760+/-210 ug/mL; p = 0.021). The
      independent risk factors for the presence of PC included male gender, previous
      peritonitis, and PD adequacy (KT/V). Further analysis performed in group 2
      patients showed that the dosage of vitamin D, serum levels of CRP, and dialysate
      calcium load were the independent determinants of PC. However, the presence of PC
      did not affect patients' technique survival, peritonitis incidence, or mortality
      in the mean follow up period of 28+/-12 months. CONCLUSIONS: The presence and
      severity of PC were associated with inflammation, peritoneal KT/V, and mineral
      metabolism. The impact of PC on the outcomes of PD patients requires further
      study with a longer follow-up.

PMID- 23977098
TI  - Loss of let-7 microRNA upregulates IL-6 in bone marrow-derived mesenchymal stem
      cells triggering a reactive stromal response to prostate cancer.
AB  - Bone marrow-derived mesenchymal stem cells (MSCs) are able to migrate to tumors,
      where they promote tumorigenesis and cancer metastasis. However, the molecular
      phenotype of the recruited MSCs at the tumor microenvironment and the genetic
      programs underlying their role in cancer progression remains largely unknown. By
      using a three-dimensional rotary wall vessel coculture system in which human MSCs
      were grown alone or in close contact with LNCaP, C4-2 or PC3 prostate cancer cell
      lines, we established in vitro matched pairs of normal and cancer-associated MSC
      derivatives to study the stromal response of MSCs to prostate cancer. We observed
      that prostate cancer-associated MSCs acquired a higher potential for adipogenic
      differentiation and exhibited a stronger ability to promote prostate cancer cell
      migration and invasion compared with normal MSCs both in vitro and in
      experimental animal models. The enhanced adipogenesis and the pro-metastatic
      properties were conferred by the high levels of IL-6 secretion by cancer
      associated MSCs and were reversible by functionally inhibiting of IL-6. We also
      found that IL-6 is a direct target gene for the let-7 microRNA, which was
      downregulated in cancer-associated MSCs. The overexpression of let-7 via the
      transfection of let-7 precursors decreased IL-6 expression and repressed the
      adipogenic potential and metastasis-promoting activity of cancer-associated MSCs,
      which was consistent with the inhibition of IL-6 3'UTR luciferase activity.
      Conversely, the treatment of normal MSCs with let-7 inhibitors resulted in
      effects similar to those seen with IL-6. Taken together, our data demonstrated
      that MSCs co-evolve with prostate cancer cells in the tumor microenvironment, and
      the downregulation of let-7 by cancer-associated MSCs upregulates IL-6
      expression. This upregulation triggers adipogenesis and facilitates prostate
      cancer progression. These findings not only provide key insights into the
      molecular basis of tumor-stroma interactions but also pave the way for new
      treatments for metastatic prostate cancer. 

PMID- 23977099
TI  - Impact of community-based larviciding on the prevalence of malaria infection in
      Dar es Salaam, Tanzania.
AB  - BACKGROUND: The use of larval source management is not prioritized by
      contemporary malaria control programs in sub-Saharan Africa despite historical
      success. Larviciding, in particular, could be effective in urban areas where
      transmission is focal and accessibility to Anopheles breeding habitats is
      generally easier than in rural settings. The objective of this study is to assess
      the effectiveness of a community-based microbial larviciding intervention to
      reduce the prevalence of malaria infection in Dar es Salaam, United Republic of
      Tanzania. METHODS AND FINDINGS: Larviciding was implemented in 3 out of 15
      targeted wards of Dar es Salaam in 2006 after two years of baseline data
      collection. This intervention was subsequently scaled up to 9 wards a year later,
      and to all 15 targeted wards in 2008. Continuous randomized cluster sampling of
      malaria prevalence and socio-demographic characteristics was carried out during 6
      survey rounds (2004-2008), which included both cross-sectional and longitudinal
      data (N = 64,537). Bayesian random effects logistic regression models were used
      to quantify the effect of the intervention on malaria prevalence at the
      individual level. Effect size estimates suggest a significant protective effect
      of the larviciding intervention. After adjustment for confounders, the odds of
      individuals living in areas treated with larviciding being infected with malaria
      were 21% lower (Odds Ratio = 0.79; 95% Credible Intervals: 0.66-0.93) than those
      who lived in areas not treated. The larviciding intervention was most effective
      during dry seasons and had synergistic effects with other protective measures
      such as use of insecticide-treated bed nets and house proofing (i.e., complete
      ceiling or window screens). CONCLUSION: A large-scale community-based larviciding
      intervention significantly reduced the prevalence of malaria infection in urban
      Dar es Salaam.

PMID- 23977100
TI  - GSTP1 Ile105Val polymorphism and prostate cancer risk: evidence from a meta
      analysis.
AB  - BACKGROUND: Glutathione S-transferase P1 (GSTP1) is thought to be involved in the
      detoxification of reactive carcinogen metabolites. Numerous epidemiological
      studies have evaluated the association of GSTP1 Ile105Val polymorphism with the
      risk of prostate cancer. However, the results remain inconclusive. To derive a
      more precise estimation, a meta-analysis was performed. METHODOLOGY/PRINCIPAL
      FINDINGS: A comprehensive search was conducted to identify the eligible studies.
      We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the
      strength of the relationship. The overall association was not significant
      (Val/Val vs. Ile/Ile OR = 1.06, 95% CI = 0.90-1.25, P = 0.50; Val/Val vs.
      Val/Ile+Ile/Ile: OR = 1.07, 95% CI = 0.91-1.25, P = 0.44). In subgroup analyses
      by ethnicity and prostate cancer grade, the similar results were observed.
      However, in stratified analysis by clinical stage, we found a significant
      association with low-stage prostate cancer (Val/Val vs. Ile/Ile: OR = 2.70, 95%
      CI = 1.73-4.22, P<0.001; Val/Val vs. Val/Ile+Ile/Ile: OR = 2.14, 95% CI = 1.38
      3.33, P = 0.001). Moreover, there was no statistically significant evidence of
      multiplicative interactions neither between the GSTP1 Ile105Val polymorphism and
      GSTM1, nor between smoking status and GSTP1 on prostate cancer risk. CONCLUSIONS:
      This meta-analysis showed that GSTP1 Ile105Val polymorphism might not be
      significantly associated with overall prostate cancer risk. Further stratified
      analyses showed a significant association with low-stage prostate cancer.

PMID- 23977101
TI  - A portable reverse transcription recombinase polymerase amplification assay for
      rapid detection of foot-and-mouth disease virus.
AB  - Foot-and-mouth disease (FMD) is a trans-boundary viral disease of livestock,
      which causes huge economic losses and constitutes a serious infectious threat for
      livestock farming worldwide. Early diagnosis of FMD helps to diminish its impact
      by adequate outbreak management. In this study, we describe the development of a
      real-time reverse transcription recombinase polymerase amplification (RT-RPA)
      assay for the detection of FMD virus (FMDV). The FMDV RT-RPA design targeted the
      3D gene of FMDV and a 260 nt molecular RNA standard was used for assay
      validation. The RT-RPA assay was fast (4-10 minutes) and the analytical
      sensitivity was determined at 1436 RNA molecules detected by probit regression
      analysis. The FMDV RT-RPA assay detected RNA prepared from all seven FMDV
      serotypes but did not detect classical swine fever virus or swine vesicular
      disease virus. The FMDV RT-RPA assay was used in the field during the recent FMD
      outbreak in Egypt. In clinical samples, reverse transcription polymerase chain
      reaction (RT-PCR) and RT-RPA showed a diagnostic sensitivity of 100% and 98%,
      respectively. In conclusion, FMDV RT-RPA was quicker and much easier to handle in
      the field than real-time RT-PCR. Thus RT-RPA could be easily implemented to
      perform diagnostics at quarantine stations or farms for rapid spot-of-infection
      detection. 

PMID- 23977102
TI  - SDS interferes with SaeS signaling of Staphylococcus aureus independently of
      SaePQ.
AB  - The Staphylococcus aureus regulatory saePQRS system controls the expression of
      numerous virulence factors, including extracellular adherence protein (Eap),
      which amongst others facilitates invasion of host cells. The saePQRS operon codes
      for 4 proteins: the histidine kinase SaeS, the response regulator SaeR, the
      lipoprotein SaeP and the transmembrane protein SaeQ. S. aureus strain Newman has
      a single amino acid substitution in the transmembrane domain of SaeS (L18P) which
      results in constitutive kinase activity. SDS was shown to be one of the signals
      interfering with SaeS activity leading to inhibition of the sae target gene eap
      in strains with SaeS(L) but causing activation in strains containing SaeS(P).
      Here, we analyzed the possible involvement of the SaeP protein and saePQ region
      in SDS-mediated sae/eap expression. We found that SaePQ is not needed for SDS
      mediated SaeS signaling. Furthermore, we could show that SaeS activity is closely
      linked to the expression of Eap and the capacity to invade host cells in a number
      of clinical isolates. This suggests that SaeS activity might be directly
      modulated by structurally non-complex environmental signals, as SDS, which
      possibly altering its kinase/phosphatase activity. 

PMID- 23977104
TI  - Soluble variants of human recombinant glutaminyl cyclase.
AB  - Recombinant human Glutaminyl Cyclase expressed in E. coli is produced as
      inclusion bodies. Lack of glycosylation is the main origin of its accumulation in
      insoluble aggregates. Mutation of single isolated hydrophobic amino acids into
      negative amino acids was not able to circumvent inclusion bodies formation. On
      the contrary, substitution with carboxyl-terminal residues of two or three
      aromatic residues belonging to extended hydrophobic patches on the protein
      surface provided soluble but still active forms of the protein. These mutants
      could be expressed in isotopically enriched forms for NMR studies and the maximal
      attainable concentration was sufficient for the acquisition of (1)H-(15)N HSQC
      spectra that represent the starting point for future drug development projects
      targeting Alzheimer's disease. 

PMID- 23977103
TI  - Novel multiplexed assay for identifying SH2 domain antagonists of STAT family
      proteins.
AB  - Some of the signal transducer and activator of transcription (STAT) family
      members are constitutively activated in a wide variety of human tumors. The
      activity of STAT depends on their Src homology 2 (SH2) domain-mediated binding to
      sequences containing phosphorylated tyrosine. Thus, antagonizing this binding is
      a feasible approach to inhibiting STAT activation. We have developed a novel
      multiplexed assay for STAT3- and STAT5b-SH2 binding, based on amplified
      luminescent proximity homogeneous assay (Alpha) technology. AlphaLISA and
      AlphaScreen beads were combined in a single-well assay, which allowed the binding
      of STAT3- and STAT5b-SH2 to phosphotyrosine peptides to be simultaneously
      monitored. Biotin-labeled recombinant human STAT proteins were obtained as N- and
      C-terminal deletion mutants. The spacer length of the DIG-labeled peptide, the
      reaction time, and the concentration of sodium chloride were optimized to
      establish a HTS system with Z' values of greater than 0.6 for both STAT3- and
      STAT5b-SH2 binding. We performed a HTS campaign for chemical libraries using this
      multiplexed assay and identified hit compounds. A 2-chloro-1,4-naphthalenedione
      derivative, Compound 1, preferentially inhibited STAT3-SH2 binding in vitro, and
      the nuclear translocation of STAT3 in HeLa cells. Initial structure activity
      relationship (SAR) studies using the multiplexed assay showed the 3-substituent
      effect on both the activity and selectivity of STAT3 and STAT5b inhibition.
      Therefore, this multiplexed assay is useful for not only searching for potential
      lead compounds but also obtaining SAR data for developing new STAT3/STAT5b
      inhibitors. 

PMID- 23977105
TI  - Urinary interleukin-8 is a biomarker of stress in emergency physicians,
      especially with advancing age--the JOBSTRESS* randomized trial.
AB  - BACKGROUND: Emergency physicians are exposed to greater stress during a 24-hour
      shift (24 hS) than a 14-hour night shift (14 hS), with an impact lasting several
      days. Interleukin-8 (IL-8) is postulated to be a chronic stress biomarker.
      However, no studies have tracked IL-8 over several shifts or used it for
      monitoring short-term residual stress. The IL-8 response to the shifts may also
      increase with age. Conveniently, IL-8 can be measured non-intrusively from urine.
      METHODS: We conducted a shifts-randomized trial comparing 17 emergency
      physicians' urinary IL-8 levels during a 24 hS, a 14 hS, and a control day
      (clerical work on return from leave). Mean levels of IL-8 were compared using a
      Wilcoxon matched-pairs test. Independent associations of key factors including
      shifts, stress, and age with IL-8 levels were further assessed in a multivariable
      generalized estimating equations model. RESULTS: Mean urinary IL-8 levels almost
      doubled during and after a 24 hS compared with a 14 hS or a control day.
      Furthermore, IL-8 levels failed to return to control values at the end of the
      third day after the shift despite a rest day following the 24 hS. In the
      multivariable model, engaging in a 24 hS, self-reported stress, and age were
      independently associated with higher IL-8 levels. A 24 hS significantly increased
      IL-8 levels by 1.9 ng (p = .007). Similarly, for every unit increase in self
      reported stress, there was a 0.11 ng increase in IL-8 levels (p = .003); and for
      every one year advance in age of physicians, IL-8 levels also increased by 0.11
      ng (p = .018). CONCLUSION: The 24 hS generated a prolonged response of the immune
      system. Urinary IL-8 was a strong biomarker of stress under intensive and
      prolonged demands, both acutely and over time. Because elevated IL-8 levels are
      associated with cardiovascular disease and negative psychological consequences,
      we suggest that emergency physicians limit their exposure to 24 hS, especially
      with advancing age.

PMID- 23977106
TI  - The effectiveness of inodilators in reducing short term mortality among patient
      with severe cardiogenic shock: a propensity-based analysis.
AB  - BACKGROUND: The best catecholamine regimen for cardiogenic shock has been poorly
      evaluated. When a vasopressor is required to treat patients with the most severe
      form of cardiogenic shock, whether inodilators should be added or whether
      inopressors can be used alone has not been established. The purpose of this study
      was to compare the impact of these two strategies on short-term mortality in
      patients with severe cardiogenic shocks. METHODS AND RESULTS: Three observational
      cohorts of patients with decompensated heart failure were pooled to comprise a
      total of 1,272 patients with cardiogenic shocks. Of these 1,272 patients, 988
      were considered to be severe because they required a vasopressor during the first
      24 hours. We developed a propensity-score (PS) model to predict the individual
      probability of receiving one of the two regimens (inopressors alone or a
      combination) conditionally on baseline-measured covariates. The benefit of the
      treatment regimen on the mortality rate was estimated by fitting a weighted Cox
      regression model. A total of 643 patients (65.1%) died within the first 30 days
      (inopressors alone: 293 (72.0%); inopressors and inodilators: 350 (60.0%)). After
      PS weighting, we observed that the use of an inopressor plus an inodilator was
      associated with an improved short-term mortality (HR: 0.66 [0.55-0.80]) compared
      to inopressors alone. CONCLUSIONS: In the most severe forms of cardiogenic shock
      where a vasopressor is immediately required, adding an inodilator may improve
      short-term mortality. This result should be confirmed in a randomized, controlled
      trial.

PMID- 23977107
TI  - High fat diet accelerates pathogenesis of murine Crohn's disease-like ileitis
      independently of obesity.
AB  - BACKGROUND: Obesity has been associated with a more severe disease course in
      inflammatory bowel disease (IBD) and epidemiological data identified dietary fats
      but not obesity as risk factors for the development of IBD. Crohn's disease is
      one of the two major IBD phenotypes and mostly affects the terminal ileum.
      Despite recent observations that high fat diets (HFD) impair intestinal barrier
      functions and drive pathobiont selection relevant for chronic inflammation in the
      colon, mechanisms of high fat diets in the pathogenesis of Crohn's disease are
      not known. The aim of this study was to characterize the effect of HFD on the
      development of chronic ileal inflammation in a murine model of Crohn's disease
      like ileitis. METHODS: TNF(DeltaARE/WT) mice and wildtype C57BL/6 littermates
      were fed a HFD compared to control diet for different durations. Intestinal
      pathology and metabolic parameters (glucose tolerance, mesenteric tissue
      characteristics) were assessed. Intestinal barrier integrity was characterized at
      different levels including polyethylene glycol (PEG) translocation, endotoxin in
      portal vein plasma and cellular markers of barrier function. Inflammatory
      activation of epithelial cells as well as immune cell infiltration into ileal
      tissue were determined and related to luminal factors. RESULTS: HFD aggravated
      ileal inflammation but did not induce significant overweight or typical metabolic
      disorders in TNF(DeltaARE/WT). Expression of the tight junction protein Occludin
      was markedly reduced in the ileal epithelium of HFD mice independently of
      inflammation, and translocation of endotoxin was increased. Epithelial cells
      showed enhanced expression of inflammation-related activation markers, along with
      enhanced luminal factors-driven recruitment of dendritic cells and Th17-biased
      lymphocyte infiltration into the lamina propria. CONCLUSIONS: HFD feeding,
      independently of obesity, accelerated disease onset of small intestinal
      inflammation in Crohn's disease-relevant mouse model through mechanisms that
      involve increased intestinal permeability and altered luminal factors, leading to
      enhanced dendritic cell recruitment and promoted Th17 immune responses.

PMID- 23977108
TI  - RuvBL2 is involved in histone deacetylase inhibitor PCI-24781-induced cell death
      in SK-N-DZ neuroblastoma cells.
AB  - Neuroblastoma is the second most common solid tumor diagnosed during infancy. The
      survival rate among children with high-risk neuroblastoma is less than 40%,
      highlighting the urgent needs for new treatment strategies. PCI-24781 is a novel
      hydroxamic acid-based histone deacetylase (HDAC) inhibitor that has high efficacy
      and safety for cancer treatment. However, the underlying mechanisms of PCI-24781
      are not clearly elucidated in neuroblastoma cells. In the present study, we
      demonstrated that PCI-24781 treatment significantly inhibited tumor growth at
      very low doses in neuroblastoma cells SK-N-DZ, not in normal cell line HS-68.
      However, PCI-24781 caused the accumulation of acetylated histone H3 both in SK-N
      DZ and HS-68 cell line. Treatment of SK-N-DZ with PCI-24781 also induced cell
      cycle arrest in G2/M phase and activated apoptosis signaling pathways via the up
      regulation of DR4, p21, p53 and caspase 3. Further proteomic analysis revealed
      differential protein expression profiles between non-treated and PCI-24781
      treated SK-N-DZ cells. Totally 42 differentially expressed proteins were
      identified by MALDI-TOF MS system. Western blotting confirmed the expression
      level of five candidate proteins including prohibitin, hHR23a, RuvBL2, TRAP1 and
      PDCD6IP. Selective knockdown of RuvBL2 rescued cells from PCI-24781-induced cell
      death, implying that RuvBL2 might play an important role in anti-tumor activity
      of PCI-24781 in SK-N-DZ cells. The present results provide a new insight into the
      potential mechanism of PCI-24781 in SK-N-DZ cell line. 

PMID- 23977110
TI  - Quantifying regional vegetation cover variability in North China during the
      Holocene: implications for climate feedback.
AB  - Validating model simulations of vegetation-climate feedback needs information not
      only on changes in past vegetation types as reconstructed by palynologists, but
      also on other proxies such as vegetation cover. We present here a quantitative
      regional vegetation cover reconstruction for North China during the Holocene. The
      reconstruction was based on 15 high-quality lake sediment profiles selected from
      55 published sites in North China, along with their modern remote sensing
      vegetation index. We used the surface soil pollen percentage to build three
      pollen-vegetation cover transfer models, and used lake surface sediment pollen
      data to validate their accuracy. Our results showed that vegetation cover in
      North China increased slightly before its maximum at 6.5 cal ka BP and has since
      declined significantly. The vegetation decline since 6.5 cal ka BP has likely
      induced a regional albedo change and aerosol increase. Further comparison with
      paleoclimate and paleovegetation dynamics in South China reproduced the regional
      cooling effect of vegetation cover decline in North China modelled in previous
      work. Our discussion demonstrates that, instead of reconstructing vegetation type
      from a single site, reconstructing quantitative regional vegetation cover could
      offer a broader understanding of regional vegetation-climate feedback. 

PMID- 23977109
TI  - Effects of multi-deficiencies-diet on bone parameters of peripheral bone in
      ovariectomized mature rat.
AB  - Many postmenopausal women have vitamin D and calcium deficiency. Therefore,
      vitamin D and calcium supplementation is recommended for all patients with
      osteopenia and osteoporosis. We used an experimental rat model to test the
      hypothesis that induction of osteoporosis is more efficiently achieved in
      peripheral bone through combining ovariectomy with a unique multi-deficiencies
      diet (vitamin D depletion and deficient calcium, vitamin K and phosphorus). 14
      week-old Sprague-Dawley rats served as controls to examine the initial bone
      status. 11 rats were bilaterally ovariectomized (OVX) and fed with multi
      deficiencies diet. Three months later the treated group and the Sham group (n =
      8) were euthanized. Bone biomechanical competence of the diaphyseal bone was
      examined on both, tibia and femur. Image analysis was performed on tibia via uCT,
      and on femur via histological analysis. Lower torsional stiffness indicated
      inferior mechanical competence of the tibia in 3 month OVX+Diet. Proximal
      metaphyseal region of the tibia showed a diminished bone tissue portion to total
      tissue in the uCT despite the increased total area as evaluated in both uCT and
      histology. Cortical bone showed higher porosity and smaller cross sectional
      thickness of the tibial diaphysis in the OVX+Diet rats. A lower ALP positive area
      and elevated serum level of RANKL exhibited the unbalanced cellular interaction
      in bone remodeling in the OVX+Diet rat after 3 month of treatment. Interestingly,
      more adipose tissue area in bone marrow indicated an effect of bone loss similar
      to that observed in osteoporotic patients. Nonetheless, the presence of osteoid
      and elevated serum level of PTH, BGP and Opn suggest the development of
      osteomalacia rather than an osteoporosis. As the treatment and fracture
      management of both osteoporotic and osteomalacia patients are clinically
      overlapping, this study provides a preclinical animal model to be utilized in
      local supplementation of minerals, drugs and growth factors in future fracture
      healing studies. 

PMID- 23977111
TI  - Partial antiviral activities detection of chicken Mx jointing with neuraminidase
      gene (NA) against Newcastle disease virus.
AB  - As an attempt to increase the resistance to Newcastle Disease Virus (NDV) and so
      further reduction of its risk on the poultry industry. This work aimed to build
      the eukaryotic gene co-expression plasmid of neuraminidase (NA) gene and myxo
      virus resistance (Mx) and detect the gene expression in transfected mouse
      fibroblasts (NIH-3T3) cells, it is most important to investigate the influence of
      the recombinant plasmid on the chicken embryonic fibroblasts (CEF) cells. cDNA
      fragment of NA and mutant Mx gene were derived from pcDNA3.0-NA and pcDNA3.0-Mx
      plasmid via PCR, respectively, then NA and Mx cDNA fragment were inserted into
      the multiple cloning sites of pVITRO2 to generate the eukaryotic co-expression
      plasmid pVITRO2-Mx-NA. The recombinant plasmid was confirmed by restriction
      endonuclease treatment and sequencing, and it was transfected into the mouse
      fibroblasts (NIH-3T3) cells. The expression of genes in pVITRO2-Mx-NA were
      measured by RT-PCR and indirect immunofluorescence assay (IFA). The recombinant
      plasmid was transfected into CEF cells then RT-PCR and the micro-cell inhibition
      tests were used to test the antiviral activity for NDV. Our results showed that
      co-expression vector pVITRO2-Mx-NA was constructed successfully; the expression
      of Mx and NA could be detected in both NIH-3T3 and CEF cells. The recombinant
      proteins of Mx and NA protect CEF cells from NDV infection until after 72 h of
      incubation but the individually mutagenic Mx protein or NA protein protects CEF
      cells from NDV infection till 48 h post-infection, and co-transfection group
      decreased significantly NDV infection compared with single-gene transfection
      group (P<0. 05), indicating that Mx-NA jointing contributed to delaying the
      infection of NDV in single-cell level and the co-transfection of the jointed
      genes was more powerful than single one due to their synergistic effects. 

PMID- 23977112
TI  - Drowning and the influence of hot weather.
AB  - BACKGROUND: Drowning deaths are devastating and preventable. Public perception
      does not regard hot weather as a common scenario for drowning deaths. The
      objective of our study was to test the association between hot weather and
      drowning risk. MATERIALS AND METHODS: We conducted a retrospective case-crossover
      analysis of all unintentional drowning deaths in Ontario, Canada from 1999 to
      2009. Demographic data were obtained from the Office of the Chief Coroner.
      Weather data were obtained from Environment Canada. We used the pair-matched
      analytic approach for the case-crossover design to contrast the weather on the
      date of the drowning with the weather at the same location one week prior
      (control period). RESULTS: We identified 1243 drowning deaths. The mean age was
      40 years, 82% were male, and most events (71%) occurred in open water. The pair
      matched analytic approach indicated that temperatures exceeding 30 degrees C were
      associated with a 69% increase in the risk of outdoor drowning (OR = 1.69, 95% CI
      1.23-2.25, p = 0.001). For indoor drowning, however, temperatures exceeding 30
      degrees C were not associated with a statistically significant increase in the
      risk of drowning (OR = 1.50, 95% CI 0.53-4.21, p = 0.442). Adult men were
      specifically prone to drown in hot weather (OR 1.67, 95% CI 1.19-2.34, p = 0.003)
      yet an apparent increase in risk extended to both genders and all age groups.
      CONCLUSION: Contrary to popular belief, hot weather rather than cold stormy
      weather increases the risk of drowning. An awareness of this risk might encourage
      greater use of drowning prevention strategies known to save lives.

PMID- 23977113
TI  - Differential DNA methylation regions in cytokine and transcription factor genomic
      loci associate with childhood physical aggression.
AB  - BACKGROUND: Animal and human studies suggest that inflammation is associated with
      behavioral disorders including aggression. We have recently shown that physical
      aggression of boys during childhood is strongly associated with reduced plasma
      levels of cytokines IL-1alpha, IL-4, IL-6, IL-8 and IL-10, later in early
      adulthood. This study tests the hypothesis that there is an association between
      differential DNA methylation regions in cytokine genes in T cells and monocytes
      DNA in adult subjects and a trajectory of physical aggression from childhood to
      adolescence. METHODOLOGY/PRINCIPAL FINDINGS: We compared the methylation profiles
      of the entire genomic loci encompassing the IL-1alpha, IL-6, IL-4, IL-10 and IL-8
      and three of their regulatory transcription factors (TF) NFkB1, NFAT5 and STAT6
      genes in adult males on a chronic physical aggression trajectory (CPA) and males
      with the same background who followed a normal physical aggression trajectory
      (control group) from childhood to adolescence. We used the method of methylated
      DNA immunoprecipitation with comprehensive cytokine gene loci and TF loci
      microarray hybridization, statistical analysis and false discovery rate
      correction. We found differentially methylated regions to associate with CPA in
      both the cytokine loci as well as in their transcription factors loci analyzed.
      Some of these differentially methylated regions were located in known regulatory
      regions whereas others, to our knowledge, were previously unknown as regulatory
      areas. However, using the ENCODE database, we were able to identify key
      regulatory elements in many of these regions that indicate that they might be
      involved in the regulation of cytokine expression. CONCLUSIONS: We provide here
      the first evidence for an association between differential DNA methylation in
      cytokines and their regulators in T cells and monocytes and male physical
      aggression.

PMID- 23977114
TI  - Cell cycle regulated phosphorylation of the telomere-associated protein TIN2.
AB  - The protein TIN2 is a member of telomere-binding protein complex that serves to
      cap and protect mammalian chromosome ends. As a number of proteins in this
      complex are phosphorylated in a cell cycle-dependent manner, we investigated
      whether TIN2 is modified by phosphorylation as well. We performed phospho
      proteomic analysis of human TIN2, and identified two phosphorylated residues,
      serines 295 and 330. We demonstrated that both these sites were phosphorylated
      during mitosis in human cells, as detected by Phos-tag reagent and
      phosphorylation-specific antibodies. Phosphorylation of serines 295 and 330
      appeared to be mediated, at least in part, by the mitotic kinase RSK2.
      Specifically, phosphorylation of TIN2 at both these residues was increased upon
      expression of RSK2 and reduced by an inhibitor of the RSK family of kinases.
      Moreover, RSK2 phosphorylated TIN2 in vitro. The identification of these
      specifically timed post-translational events during the cell cycle suggests a
      potential mitotic regulation of TIN2 by phosphorylation. 

PMID- 23977115
TI  - Looking time predicts choice but not aesthetic value.
AB  - Although visual fixations are commonly used to index stimulus-driven or
      internally-determined preference, recent evidence suggests that visual fixations
      can also be a source of decisional bias that moves selection toward the fixated
      object. These contrasting results raise the question of whether visual fixations
      always index comparative processes during choice-based tasks, or whether they
      might better reflect internal preferences when the decision does not carry any
      economic or corporeal consequences. In two experiments, participants chose which
      of two objects were more aesthetically pleasing (Exp.1) or appeared more organic
      (Exp.2), and provided independent aesthetic ratings of the stimuli. Our results
      demonstrated that fixation parameters were a better index of choice in both
      decisional domains than of aesthetic preference. The data support models in which
      visual fixations are specifically related to the evolution of decision processes
      even when the decision has no tangible consequences. 

PMID- 23977116
TI  - Multiple causes of fatigue during shortening contractions in rat slow twitch
      skeletal muscle.
AB  - Fatigue in muscles that shorten might have other causes than fatigue during
      isometric contractions, since both cross-bridge cycling and energy demand are
      different in the two exercise modes. While isometric contractions are extensively
      studied, the causes of fatigue in shortening contractions are poorly mapped.
      Here, we investigate fatigue mechanisms during shortening contractions in slow
      twitch skeletal muscle in near physiological conditions. Fatigue was induced in
      rat soleus muscles with maintained blood supply by in situ shortening
      contractions at 37 degrees C. Muscles were stimulated repeatedly (1 s on/off at
      30 Hz) for 15 min against a constant load, allowing the muscle to shorten and
      perform work. Fatigue and subsequent recovery was examined at 20 s, 100 s and 15
      min exercise. The effects of prior exercise were investigated in a second
      exercise bout. Fatigue developed in three distinct phases. During the first 20 s
      the regulatory protein Myosin Light Chain-2 (slow isoform, MLC-2s) was rapidly
      dephosphorylated in parallel with reduced rate of force development and reduced
      shortening. In the second phase there was degradation of high-energy phosphates
      and accumulation of lactate, and these changes were related to slowing of muscle
      relengthening and relaxation, culminating at 100 s exercise. Slowing of
      relaxation was also associated with increased leak of calcium from the SR. During
      the third phase of exercise there was restoration of high-energy phosphates and
      elimination of lactate, and the slowing of relaxation disappeared, whereas
      dephosphorylation of MLC-2s and reduced shortening prevailed. Prior exercise
      improved relaxation parameters in a subsequent exercise bout, and we propose that
      this effect is a result of less accumulation of lactate due to more rapid onset
      of oxidative metabolism. The correlation between dephosphorylation of MLC-2s and
      reduced shortening was confirmed in various experimental settings, and we suggest
      MLC-2s as an important regulator of muscle shortening. 

PMID- 23977117
TI  - Cerebral blood volume calculated by dynamic susceptibility contrast-enhanced
      perfusion MR imaging: preliminary correlation study with glioblastoma genetic
      profiles.
AB  - PURPOSE: To evaluate the usefulness of dynamic susceptibility contrast (DSC)
      enhanced perfusion MR imaging in predicting major genetic alterations in
      glioblastomas. MATERIALS AND METHODS: Twenty-five patients (M:F = 13?12, mean
      age: 52.1+/-15.2 years) with pathologically proven glioblastoma who underwent DSC
      MR imaging before surgery were included. On DSC MR imaging, the normalized
      relative tumor blood volume (nTBV) of the enhancing solid portion of each tumor
      was calculated by using dedicated software (Nordic TumorEX, NordicNeuroLab,
      Bergen, Norway) that enabled semi-automatic segmentation for each tumor. Five
      major glioblastoma genetic alterations (epidermal growth factor receptor (EGFR),
      phosphatase and tensin homologue (PTEN), Ki-67, O6-methylguanine-DNA
      methyltransferase (MGMT) and p53) were confirmed by immunohistochemistry and
      analyzed for correlation with the nTBV of each tumor. Statistical analysis was
      performed using the unpaired Student t test, ROC (receiver operating
      characteristic) curve analysis and Pearson correlation analysis. RESULTS: The
      nTBVs of the MGMT methylation-negative group (mean 9.5+/-7.5) were significantly
      higher than those of the MGMT methylation-positive group (mean 5.4+/-1.8) (p =
      .046). In the analysis of EGFR expression-positive group, the nTBVs of the
      subgroup with loss of PTEN gene expression (mean: 10.3+/-8.1) were also
      significantly higher than those of the subgroup without loss of PTEN gene
      expression (mean: 5.6+/-2.3) (p = .046). Ki-67 labeling index indicated
      significant positive correlation with the nTBV of the tumor (p = .01).
      CONCLUSION: We found that glioblastomas with aggressive genetic alterations
      tended to have a high nTBV in the present study. Thus, we believe that DSC
      enhanced perfusion MR imaging could be helpful in predicting genetic alterations
      that are crucial in predicting the prognosis of and selecting tailored treatment
      for glioblastoma patients.

PMID- 23977118
TI  - High-throughput analysis of stimulus-evoked behaviors in Drosophila larva reveals
      multiple modality-specific escape strategies.
AB  - All organisms react to noxious and mechanical stimuli but we still lack a
      complete understanding of cellular and molecular mechanisms by which
      somatosensory information is transformed into appropriate motor outputs. The
      small number of neurons and excellent genetic tools make Drosophila larva an
      especially tractable model system in which to address this problem. We developed
      high throughput assays with which we can simultaneously expose more than 1,000
      larvae per man-hour to precisely timed noxious heat, vibration, air current, or
      optogenetic stimuli. Using this hardware in combination with custom software we
      characterized larval reactions to somatosensory stimuli in far greater detail
      than possible previously. Each stimulus evoked a distinctive escape strategy that
      consisted of multiple actions. The escape strategy was context-dependent. Using
      our system we confirmed that the nociceptive class IV multidendritic neurons were
      involved in the reactions to noxious heat. Chordotonal (ch) neurons were
      necessary for normal modulation of head casting, crawling and hunching, in
      response to mechanical stimuli. Consistent with this we observed increases in
      calcium transients in response to vibration in ch neurons. Optogenetic activation
      of ch neurons was sufficient to evoke head casting and crawling. These studies
      significantly increase our understanding of the functional roles of larval ch
      neurons. More generally, our system and the detailed description of wild type
      reactions to somatosensory stimuli provide a basis for systematic identification
      of neurons and genes underlying these behaviors. 

PMID- 23977119
TI  - Boron nitride nanotube-mediated stimulation of cell co-culture on micro
      engineered hydrogels.
AB  - In this paper, we describe the effects of the combination of topographical,
      mechanical, chemical and intracellular electrical stimuli on a co-culture of
      fibroblasts and skeletal muscle cells. The co-culture was anisotropically grown
      onto an engineered micro-grooved (10 um-wide grooves) polyacrylamide substrate,
      showing a precisely tuned Young's modulus (~ 14 kPa) and a small thickness (~ 12
      um). We enhanced the co-culture properties through intracellular stimulation
      produced by piezoelectric nanostructures (i.e., boron nitride nanotubes)
      activated by ultrasounds, thus exploiting the ability of boron nitride nanotubes
      to convert outer mechanical waves (such as ultrasounds) in intracellular
      electrical stimuli, by exploiting the direct piezoelectric effect. We
      demonstrated that nanotubes were internalized by muscle cells and localized in
      both early and late endosomes, while they were not internalized by the underneath
      fibroblast layer. Muscle cell differentiation benefited from the synergic
      combination of topographical, mechanical, chemical and nanoparticle-based
      stimuli, showing good myotube development and alignment towards a preferential
      direction, as well as high expression of genes encoding key proteins for muscle
      contraction (i.e., actin and myosin). We also clarified the possible role of
      fibroblasts in this process, highlighting their response to the above mentioned
      physical stimuli in terms of gene expression and cytokine production. Finally,
      calcium imaging-based experiments demonstrated a higher functionality of the
      stimulated co-cultures. 

PMID- 23977120
TI  - Land use planning and wildfire: development policies influence future probability
      of housing loss.
AB  - Increasing numbers of homes are being destroyed by wildfire in the wildland-urban
      interface. With projections of climate change and housing growth potentially
      exacerbating the threat of wildfire to homes and property, effective fire-risk
      reduction alternatives are needed as part of a comprehensive fire management
      plan. Land use planning represents a shift in traditional thinking from trying to
      eliminate wildfires, or even increasing resilience to them, toward avoiding
      exposure to them through the informed placement of new residential structures.
      For land use planning to be effective, it needs to be based on solid
      understanding of where and how to locate and arrange new homes. We simulated
      three scenarios of future residential development and projected landscape-level
      wildfire risk to residential structures in a rapidly urbanizing, fire-prone
      region in southern California. We based all future development on an econometric
      subdivision model, but we varied the emphasis of subdivision decision-making
      based on three broad and common growth types: infill, expansion, and leapfrog.
      Simulation results showed that decision-making based on these growth types, when
      applied locally for subdivision of individual parcels, produced substantial
      landscape-level differences in pattern, location, and extent of development.
      These differences in development, in turn, affected the area and proportion of
      structures at risk from burning in wildfires. Scenarios with lower housing
      density and larger numbers of small, isolated clusters of development, i.e.,
      resulting from leapfrog development, were generally predicted to have the highest
      predicted fire risk to the largest proportion of structures in the study area,
      and infill development was predicted to have the lowest risk. These results
      suggest that land use planning should be considered an important component to
      fire risk management and that consistently applied policies based on residential
      pattern may provide substantial benefits for future risk reduction. 

PMID- 23977121
TI  - WISP1/CCN4: a potential target for inhibiting prostate cancer growth and spread
      to bone.
AB  - Prostate cancer (PC) is a leading cause of death in men however the factors that
      regulate its progression and eventual metastasis to bone remain unclear. Here we
      show that WISP1/CCN4 expression in prostate cancer tissues was up-regulated in
      early stages of the disease and, further, that it correlated with increased
      circulating levels of WISP1 in the sera of patients at early stages of the
      disease. WISP1 was also elevated in the mouse prostate cancer model TRAMP in the
      hypoplastic diseased tissue that develops prior to advanced carcinoma formation.
      When the ability of anti-WISP1 antibodies to reduce the spread of PC3-Luc cells
      to distant sites was tested it showed that twice weekly injections of anti-WISP1
      antibodies reduced the number and overall size of distant tumors developed after
      intracardiac (IC) injection of PC3-Luc cells in mice. The ability of antibodies
      against WISP1 to inhibit growth of PC3-Luc cancer cells in mice was also
      evaluated and showed that twice weekly injections of anti-WISP1 antibodies
      reduced local tumor growth when examined in xenografts. To better understand the
      mechanism of action, the migration of PC3-Luc cells through membranes with or
      without a MatrigelTM barrier showed the cells were attracted to WISP1, and that
      this attraction was inhibited by treatment with anti-WISP1 antibodies. We also
      show the expression of WISP1 at the bone-tumor interface and in the stroma of
      early grade cancers suggested WISP1 expression is well placed to play roles in
      both fostering growth of the cancer and its spread to bone. In summary, the up
      regulation of WISP1 in the early stages of cancer development coupled with its
      ability to inhibit spread and growth of prostate cancer cells makes it both a
      potential target and an accessible diagnostic marker for prostate cancer. 

PMID- 23977122
TI  - Barcoding poplars (Populus L.) from western China.
AB  - BACKGROUND: Populus is an ecologically and economically important genus of trees,
      but distinguishing between wild species is relatively difficult due to extensive
      interspecific hybridization and introgression, and the high level of
      intraspecific morphological variation. The DNA barcoding approach is a potential
      solution to this problem. METHODOLOGY/PRINCIPAL FINDINGS: Here, we tested the
      discrimination power of five chloroplast barcodes and one nuclear barcode (ITS)
      among 95 trees that represent 21 Populus species from western China. Among all
      single barcode candidates, the discrimination power is highest for the nuclear
      ITS, progressively lower for chloroplast barcodes matK (M), trnG-psbK (G) and
      psbK-psbI (P), and trnH-psbA (H) and rbcL (R); the discrimination efficiency of
      the nuclear ITS (I) is also higher than any two-, three-, or even the five-locus
      combination of chloroplast barcodes. Among the five combinations of a single
      chloroplast barcode plus the nuclear ITS, H+I and P+I differentiated the highest
      and lowest portion of species, respectively. The highest discrimination rate for
      the barcodes or barcode combinations examined here is 55.0% (H+I), and usually
      discrimination failures occurred among species from sympatric or parapatric
      areas. CONCLUSIONS/SIGNIFICANCE: In this case study, we showed that when
      discriminating Populus species from western China, the nuclear ITS region
      represents a more promising barcode than any maternally inherited chloroplast
      region or combination of chloroplast regions. Meanwhile, combining the ITS region
      with chloroplast regions may improve the barcoding success rate and assist in
      detecting recent interspecific hybridizations. Failure to discriminate among
      several groups of Populus species from sympatric or parapatric areas may have
      been the result of incomplete lineage sorting, frequent interspecific
      hybridizations and introgressions. We agree with a previous proposal for
      constructing a tiered barcoding system in plants, especially for taxonomic groups
      that have complex evolutionary histories (e.g. Populus).

PMID- 23977123
TI  - Machine learning of hierarchical clustering to segment 2D and 3D images.
AB  - We aim to improve segmentation through the use of machine learning tools during
      region agglomeration. We propose an active learning approach for performing
      hierarchical agglomerative segmentation from superpixels. Our method combines
      multiple features at all scales of the agglomerative process, works for data with
      an arbitrary number of dimensions, and scales to very large datasets. We advocate
      the use of variation of information to measure segmentation accuracy,
      particularly in 3D electron microscopy (EM) images of neural tissue, and using
      this metric demonstrate an improvement over competing algorithms in EM and
      natural images. 

PMID- 23977124
TI  - Reactive-oxygen-species-mediated P. aeruginosa killing is functional in human
      cystic fibrosis macrophages.
AB  - Pseudomonas aeruginosa is the most common pathogen for chronic lung infection in
      cystic fibrosis (CF) patients. About 80% of adult CF patients have chronic P.
      aeruginosa infection, which accounts for much of the morbidity and most of the
      mortality. Both bacterial genetic adaptations and defective innate immune
      responses contribute to the bacteria persistence. It is well accepted that CF
      transmembrane conductance regulator (CFTR) dysfunction impairs the airways
      epithelium-mediated lung defence; however, other innate immune cells also appear
      to be affected, such as neutrophils and macrophages, which thus contribute to
      this infectious pathology in the CF lung. In macrophages, the absence of CFTR has
      been linked to defective P. aeruginosa killing, increased pro-inflammatory
      cytokine secretion, and reduced reactive oxygen species (ROS) production. To
      learn more about macrophage dysfunction in CF patients, we investigated the
      generation of the oxidative burst and its impact on bacterial killing in CF
      macrophages isolated from peripheral blood or lung parenchyma of CF patients,
      after P. aeruginosa infection. Our data demonstrate that CF macrophages show an
      oxidative response of similar intensity to that of non-CF macrophages.
      Intracellular ROS are recognized as one of the earliest microbicidal mechanisms
      against engulfed pathogens that are activated by macrophages. Accordingly, NADPH
      inhibition resulted in a significant increase in the intracellular bacteria
      survival in CF and non-CF macrophages, both as monocyte-derived macrophages and
      as lung macrophages. These data strongly suggest that the contribution of ROS to
      P. aeruginosa killing is not affected by CFTR mutations. 

PMID- 23977125
TI  - Erythropoiesis suppression is associated with anthrax lethal toxin-mediated
      pathogenic progression.
AB  - Anthrax is a disease caused by the bacterium Bacillus anthracis, which results in
      high mortality in animals and humans. Although some of the mechanisms are already
      known such as asphyxia, extensive knowledge of molecular pathogenesis of this
      disease is deficient and remains to be further investigated. Lethal toxin (LT) is
      a major virulence factor of B. anthracis and a specific inhibitor/protease of
      mitogen-activated protein kinase kinases (MAPKKs). Anthrax LT causes lethality
      and induces certain anthrax-like symptoms, such as anemia and hypoxia, in
      experimental mice. Mitogen-activated protein kinases (MAPKs) are the downstream
      pathways of MAPKKs, and are important for erythropoiesis. This prompted us to
      hypothesize that anemia and hypoxia may in part be exacerbated by erythropoietic
      dysfunction. As revealed by colony-forming cell assays in this study, LT
      challenges significantly reduced mouse erythroid progenitor cells. In addition,
      in a proteolytic activity-dependent manner, LT suppressed cell survival and
      differentiation of cord blood CD34(+)-derived erythroblasts in vitro. Suppression
      of cell numbers and the percentage of erythroblasts in the bone marrow were
      detected in LT-challenged C57BL/6J mice. In contrast, erythropoiesis was provoked
      through treatments of erythropoietin, significantly ameliorating the anemia and
      reducing the mortality of LT-treated mice. These data suggested that suppressed
      erythropoiesis is part of the pathophysiology of LT-mediated intoxication.
      Because specific treatments to overcome LT-mediated pathogenesis are still
      lacking, these efforts may help the development of effective treatments against
      anthrax. 

PMID- 23977126
TI  - ESBL-producing Enterobacteriaceae: occurrence, risk factors for fecal carriage
      and strain traits in the Swiss slaughter cattle population younger than 2 years
      sampled at abattoir level.
AB  - During the past decade extended-spectrum beta-lactamase (ESBL) producing
      Enterobacteriaceae have become a matter of great concern in human and veterinary
      medicine. In this cross-sectional study fecal swabs of a geographically
      representative number of Swiss cattle at slaughterhouse level were sampled i) to
      determine the occurrence of ESBL producing Enterobacteriaceae in the Swiss
      slaughter cattle population younger than 2 years, and ii) to assess risk factors
      for shedding ESBL producing Enterobacteriaceae. In total, 48 (8.4%; 95% C.I. 6.3
      11.1%) independent ESBL producing Enterobacteriaceae were detected among the 571
      tested animals. Species identification revealed 46 E. coli strains, one
      Enterobacter cloacae and one Citrobacter youngae. In view of beta-lactam
      antibiotics, all 48 isolates were resistant to ampicillin, cephalothin and
      cefpodoxime. Forty-five (93.8%) isolates were resistant cefuroxime; one (2.1%)
      isolate to cefoxitin, 28 (58.3%) isolates to cefotaxime, 2 (4.2%) isolates to
      ceftazidime, and 2 (4.2%) isolates to cefepime. Risk factors for shedding ESBL
      producing Enterobacteriaceae were (i) age (OR 0.19 and 0.12 in age category 181 d
      to 1 y and 1 y to 2 y compared to <=180 d), (ii) primary production type, meaning
      dairy compared to beef on farm of origin (OR 5.95), and (iii) more than 1
      compared to less than 1 animal movement per d per 100 animals on farm of origin
      (OR 2.37).

PMID- 23977128
TI  - Food-web structure in relation to environmental gradients and predator-prey
      ratios in tank-bromeliad ecosystems.
AB  - Little is known of how linkage patterns between species change along
      environmental gradients. The small, spatially discrete food webs inhabiting tank
      bromeliads provide an excellent opportunity to analyse patterns of community
      diversity and food-web topology (connectance, linkage density, nestedness) in
      relation to key environmental variables (habitat size, detrital resource,
      incident radiation) and predators:prey ratios. We sampled 365 bromeliads in a
      wide range of understorey environments in French Guiana and used gut contents of
      invertebrates to draw the corresponding 365 connectance webs. At the bromeliad
      scale, habitat size (water volume) determined the number of species that
      constitute food-web nodes, the proportion of predators, and food-web topology.
      The number of species as well as the proportion of predators within bromeliads
      declined from open to forested habitats, where the volume of water collected by
      bromeliads was generally lower because of rainfall interception by the canopy. A
      core group of microorganisms and generalist detritivores remained relatively
      constant across environments. This suggests that (i) a highly-connected core
      ensures food-web stability and key ecosystem functions across environments, and
      (ii) larger deviations in food-web structures can be expected following
      disturbance if detritivores share traits that determine responses to
      environmental changes. While linkage density and nestedness were lower in
      bromeliads in the forest than in open areas, experiments are needed to confirm a
      trend for lower food-web stability in the understorey of primary forests. 

PMID- 23977127
TI  - Conformational changes in the lower palm domain of ASIC1a contribute to
      desensitization and RFamide modulation.
AB  - Acid-sensing ion channel 1a (ASIC1a) is a proton-gated cation channel that
      contributes to fear and pain as well as neuronal damage following persistent
      cerebral acidosis. Neuropeptides can affect acid-induced neuronal injury by
      altering ASIC1a inactivation and/or steady-state desensitization. Yet, exactly
      how ASIC1a inactivation and desensitization occur or are modulated by peptides is
      not completely understood. We found that regions of the extracellular palm domain
      and the beta(11-12) linker are important for inactivation and steady-state
      desensitization of ASIC1a. The single amino acid substitutions L280C and L415C
      dramatically enhanced the rate of inactivation and altered the pH-dependence of
      steady-state desensitization. Further, the use of methanethiosulfonate (MTS)
      reagents suggests that the lower palm region (L280C) undergoes a conformational
      change when ASIC1a transitions from closed to desensitized. We determined that
      L280C also displays an altered response to the RFamide peptide, FRRFamide.
      Further, the presence of FRRFamide limited MTS modification of L280C. Together,
      these results indicate a potential role of the lower palm domain in peptide
      modulation and suggest RFamide-related peptides promote conformational changes
      within this region. These data provide empirical support for the idea that L280,
      and likely this region of the central vestibule, is intimately involved in
      channel inactivation and desensitization.

PMID- 23977129
TI  - Raman spectroscopic imaging of the whole Ciona intestinalis embryo during
      development.
AB  - Intracellular composition and the distribution of bio-molecules play central
      roles in the specification of cell fates and morphogenesis during embryogenesis.
      Consequently, investigation of changes in the expression and distribution of bio
      molecules, especially mRNAs and proteins, is an important challenge in
      developmental biology. Raman spectroscopic imaging, a non-invasive and label-free
      technique, allows simultaneous imaging of the intracellular composition and
      distribution of multiple bio-molecules. In this study, we explored the
      application of Raman spectroscopic imaging in the whole Ciona intestinalis embryo
      during development. Analysis of Raman spectra scattered from C. intestinalis
      embryos revealed a number of localized patterns of high Raman intensity within
      the embryo. Based on the observed distribution of bio-molecules, we succeeded in
      identifying the location and structure of differentiated muscle and endoderm
      within the whole embryo, up to the tailbud stage, in a label-free manner.
      Furthermore, during cell differentiation, we detected significant differences in
      cell state between muscle/endoderm daughter cells and daughter cells with other
      fates that had divided from the same mother cells; this was achieved by focusing
      on the Raman intensity of single Raman bands at 1002 or 1526 cm(-1),
      respectively. This study reports the first application of Raman spectroscopic
      imaging to the study of identifying and characterizing differentiating tissues in
      a whole chordate embryo. Our results suggest that Raman spectroscopic imaging is
      a feasible label-free technique for investigating the developmental process of
      the whole embryo of C. intestinalis. 

PMID- 23977130
TI  - The effects of mechanical loading on tendons--an in vivo and in vitro model
      study.
AB  - Mechanical loading constantly acts on tendons, and a better understanding of its
      effects on the tendons is essential to gain more insights into tendon patho
      physiology. This study aims to investigate tendon mechanobiological responses
      through the use of mouse treadmill running as an in vivo model and mechanical
      stretching of tendon cells as an in vitro model. In the in vivo study, mice
      underwent moderate treadmill running (MTR) and intensive treadmill running (ITR)
      regimens. Treadmill running elevated the expression of mechanical growth factors
      (MGF) and enhanced the proliferative potential of tendon stem cells (TSCs) in
      both patellar and Achilles tendons. In both tendons, MTR upregulated tenocyte
      related genes: collagen type I (Coll. I ~10 fold) and tenomodulin (~3-4 fold),
      but did not affect non-tenocyte-related genes: LPL (adipocyte), Sox9
      (chondrocyte), Runx2 and Osterix (both osteocyte). However, ITR upregulated both
      tenocyte (Coll. I ~7-11 fold; tenomodulin ~4-5 fold) and non-tenocyte-related
      genes (~3-8 fold). In the in vitro study, TSCs and tenocytes were stretched to 4%
      and 8% using a custom made mechanical loading system. Low mechanical stretching
      (4%) of TSCs from both patellar and Achilles tendons increased the expression of
      only the tenocyte-related genes (Coll. I ~5-6 fold; tenomodulin ~6-13 fold), but
      high mechanical stretching (8%) increased the expression of both tenocyte (Coll.
      I ~28-50 fold; tenomodulin ~14-48 fold) and non-tenocyte-related genes (2-5
      fold). However, in tenocytes, non-tenocyte related gene expression was not
      altered by the application of either low or high mechanical stretching. These
      findings indicate that appropriate mechanical loading could be beneficial to
      tendons because of their potential to induce anabolic changes in tendon cells.
      However, while excessive mechanical loading caused anabolic changes in tendons,
      it also induced differentiation of TSCs into non-tenocytes, which may lead to the
      development of degenerative tendinopathy frequently seen in clinical settings. 

PMID- 23977131
TI  - Snowflake vitreoretinal degeneration (SVD) mutation R162W provides new insights
      into Kir7.1 ion channel structure and function.
AB  - Snowflake Vitreoretinal Degeneration (SVD) is associated with the R162W mutation
      of the Kir7.1 inwardly-rectifying potassium channel. Kir7.1 is found at the
      apical membrane of Retinal Pigment Epithelial (RPE) cells, adjacent to the
      photoreceptor neurons. The SVD phenotype ranges from RPE degeneration to an
      abnormal b-wave to a liquid vitreous. We sought to determine how this mutation
      alters the structure and function of the human Kir7.1 channel. In this study, we
      expressed a Kir7.1 construct with the R162W mutation in CHO cells to evaluate
      function of the ion channel. Compared to the wild-type protein, the mutant
      protein exhibited a non-functional Kir channel that resulted in depolarization of
      the resting membrane potential. Upon co-expression with wild-type Kir7.1, R162W
      mutant showed a reduction of IKir7.1 and positive shift in '0' current potential.
      Homology modeling based on the structure of a bacterial Kir channel protein
      suggested that the effect of R162W mutation is a result of loss of hydrogen
      bonding by the regulatory lipid binding domain of the cytoplasmic structure. 

PMID- 23977132
TI  - Impact of library preparation on downstream analysis and interpretation of RNA
      Seq data: comparison between Illumina PolyA and NuGEN Ovation protocol.
AB  - OBJECTIVES: The sequencing by the PolyA selection is the most common approach for
      library preparation. With limited amount or degraded RNA, alternative protocols
      such as the NuGEN have been developed. However, it is not yet clear how the
      different library preparations affect the downstream analyses of the broad
      applications of RNA sequencing. METHODS AND MATERIALS: Eight human mammary
      epithelial cell (HMEC) lines with high quality RNA were sequenced by Illumina's
      mRNA-Seq PolyA selection and NuGEN ENCORE library preparation. The following
      analyses and comparisons were conducted: 1) the numbers of genes captured by each
      protocol; 2) the impact of protocols on differentially expressed gene detection
      between biological replicates; 3) expressed single nucleotide variant (SNV)
      detection; 4) non-coding RNAs, particularly lincRNA detection; and 5) intragenic
      gene expression. RESULTS: Sequences from the NuGEN protocol had lower (75%)
      alignment rate than the PolyA (over 90%). The NuGEN protocol detected fewer genes
      (12-20% less) with a significant portion of reads mapped to non-coding regions. A
      large number of genes were differentially detected between the two protocols.
      About 17-20% of the differentially expressed genes between biological replicates
      were commonly detected between the two protocols. Significantly higher numbers of
      SNVs (5-6 times) were detected in the NuGEN samples, which were largely from
      intragenic and intergenic regions. The NuGEN captured fewer exons (25% less) and
      had higher base level coverage variance. While 6.3% of reads were mapped to
      intragenic regions in the PolyA samples, the percentages were much higher (20
      25%) for the NuGEN samples. The NuGEN protocol did not detect more known non
      coding RNAs such as lincRNAs, but targeted small and "novel" lincRNAs.
      CONCLUSION: Different library preparations can have significant impacts on
      downstream analysis and interpretation of RNA-seq data. The NuGEN provides an
      alternative for limited or degraded RNA but it has limitations for some RNA-seq
      applications.

PMID- 23977133
TI  - A missing PD-L1/PD-1 coinhibition regulates diabetes induction by preproinsulin
      specific CD8 T-cells in an epitope-specific manner.
AB  - Coinhibitory PD-1/PD-L1 (B7-H1) interactions provide critical signals for the
      regulation of autoreactive T-cell responses. We established mouse models,
      expressing the costimulator molecule B7.1 (CD80) on pancreatic beta cells (RIP
      B7.1 tg mice) or are deficient in coinhibitory PD-L1 or PD-1 molecules (PD-L1(-/
      ) and PD-1(-/-) mice), to study induction of preproinsulin (ppins)-specific CD8 T
      cell responses and experimental autoimmune diabetes (EAD) by DNA-based
      immunization. RIP-B7.1 tg mice allowed us to identify two CD8 T-cell
      specificities: pCI/ppins DNA exclusively induced K(b)/A(12-21)-specific CD8 T
      cells and EAD, whereas pCI/ppinsDeltaA(12-21) DNA (encoding ppins without the
      COOH-terminal A(12-21) epitope) elicited K(b)/B(22-29)-specific CD8 T-cells and
      EAD. Specific expression/processing of mutant ppinsDeltaA(12-21) (but not ppins)
      in non-beta cells, targeted by intramuscular DNA-injection, thus facilitated
      induction of K(b)/B(22-29)-specific CD8 T-cells. The A(12-21) epitope binds K(b)
      molecules with a very low avidity as compared with B(22-29). Interestingly,
      immunization of coinhibition-deficient PD-L1(-/-) or PD-1(-/-) mice with
      pCI/ppins induced K(b)/A(12-21)-monospecific CD8 T-cells and EAD but injections
      with pCI/ppinsDeltaA(12-21) did neither recruit K(b)/B(22-29)-specific CD8 T
      cells into the pancreatic target tissue nor induce EAD. PpinsDeltaA(12
      21)/(K(b)/B(22-29))-mediated EAD was efficiently restored in RIP-B7.1(+)/PD-L1(-/
      ) mice, differing from PD-L1(-/-) mice only in the tg B7.1 expression in beta
      cells. Alternatively, an ongoing beta cell destruction and tissue inflammation,
      initiated by ppins/(K(b)/A(12-21))-specific CD8 T-cells in
      pCI/ppins+pCI/ppinsDeltaA(12-21) co-immunized PD-L1(-/-) mice, facilitated the
      expansion of ppinsDeltaA(12-21)/(K(b)/B(22-29))-specific CD8 T-cells. CD8 T-cells
      specific for the high-affinity K(b)/B(22-29)- (but not the low-affinity K(b)/A(12
      21))-epitope thus require stimulatory help from beta cells or inflamed islets to
      expand in PD-L1-deficient mice. The new PD-1/PD-L1 diabetes models may be
      valuable tools to study under well controlled experimental conditions distinct
      hierarchies of autoreactive CD8 T-cell responses, which trigger the initial steps
      of beta cell destruction or emerge during the pathogenic progression of EAD.

PMID- 23977135
TI  - Patterns of plant biomass allocation in temperate grasslands across a 2500-km
      transect in northern China.
AB  - Plant biomass allocation between below- and above-ground parts can actively adapt
      to the ambient growth conditions and is a key parameter for estimating
      terrestrial ecosystem carbon (C) stocks. To investigate how climatic variations
      affect patterns of plant biomass allocation, we sampled 548 plants belonging to
      four dominant genera (Stipa spp., Cleistogenes spp., Agropyron spp., and Leymus
      spp.) along a large-scale (2500 km) climatic gradient across the temperate
      grasslands from west to east in northern China. Our results showed that Leymus
      spp. had the lowest root/shoot ratios among the each genus. Root/shoot ratios of
      each genera were positively correlated with mean annual temperature (MAT), and
      negatively correlated with mean annual precipitation (MAP) across the transect.
      Temperature contributed more to the variation of root/shoot ratios than
      precipitation for Cleistogenes spp. (C4 plants), whereas precipitation exerted a
      stronger influence than temperature on their variations for the other three
      genera (C3 plants). From east to west, investment of C into the belowground parts
      increased as precipitation decreased while temperature increased. Such changes in
      biomass allocation patterns in response to climatic factors may alter the
      competition regimes among co-existing plants, resulting in changes in community
      composition, structure and ecosystem functions. Our results suggested that future
      climate change would have great impact on C allocation and storage, as well as C
      turnover in the grassland ecosystems in northern China. 

PMID- 23977134
TI  - Characterization of FKGK18 as inhibitor of group VIA Ca2+-independent
      phospholipase A2 (iPLA2beta): candidate drug for preventing beta-cell apoptosis
      and diabetes.
AB  - Ongoing studies suggest an important role for iPLA2beta in a multitude of
      biological processes and it has been implicated in neurodegenerative, skeletal
      and vascular smooth muscle disorders, bone formation, and cardiac arrhythmias.
      Thus, identifying an iPLA2betainhibitor that can be reliably and safely used in
      vivo is warranted. Currently, the mechanism-based inhibitor bromoenol lactone
      (BEL) is the most widely used to discern the role of iPLA2beta in biological
      processes. While BEL is recognized as a more potent inhibitor of iPLA2 than of
      cPLA2 or sPLA2, leading to its designation as a "specific" inhibitor of iPLA2, it
      has been shown to also inhibit non-PLA2 enzymes. A potential complication of its
      use is that while the S and R enantiomers of BEL exhibit preference for cytosol
      associated iPLA2beta and membrane-associated iPLA2gamma, respectively, the
      selectivity is only 10-fold for both. In addition, BEL is unstable in solution,
      promotes irreversible inhibition, and may be cytotoxic, making BEL not amenable
      for in vivo use. Recently, a fluoroketone (FK)-based compound (FKGK18) was
      described as a potent inhibitor of iPLA2beta. Here we characterized its
      inhibitory profile in beta-cells and find that FKGK18: (a) inhibits iPLA2beta
      with a greater potency (100-fold) than iPLA2gamma, (b) inhibition of iPLA2beta is
      reversible, (c) is an ineffective inhibitor of alpha-chymotrypsin, and (d)
      inhibits previously described outcomes of iPLA2beta activation including (i)
      glucose-stimulated insulin secretion, (ii) arachidonic acid hydrolysis; as
      reflected by PGE2 release from human islets, (iii) ER stress-induced neutral
      sphingomyelinase 2 expression, and (iv) ER stress-induced beta-cell apoptosis.
      These findings suggest that FKGK18 is similar to BEL in its ability to inhibit
      iPLA2beta. Because, in contrast to BEL, it is reversible and not a non-specific
      inhibitor of proteases, it is suggested that FKGK18 is more ideal for ex vivo and
      in vivo assessments of iPLA2beta role in biological functions. 

PMID- 23977136
TI  - Acinetobacter baumannii outer membrane vesicles elicit a potent innate immune
      response via membrane proteins.
AB  - Acinetobacter baumannii is increasingly becoming a major nosocomial pathogen.
      This opportunistic pathogen secretes outer membrane vesicles (OMVs) that interact
      with host cells. The aim of this study was to investigate the ability of A.
      baumannii OMVs to elicit a pro-inflammatory response in vitro and the
      immunopathology in response to A. baumannii OMVs in vivo. OMVs derived from A.
      baumannii ATCC 19606(T) induced expression of pro-inflammatory cytokine genes,
      interleukin (IL)-1beta and IL-6, and chemokine genes, IL-8, macrophage
      inflammatory protein-1alpha, and monocyte chemoattractant protein-1, in
      epithelial cells in a dose-dependent manner. Disintegration of OMV membrane with
      ethylenediaminetetraacetic acid resulted in low expression of pro-inflammatory
      cytokine genes, as compared with the response to intact OMVs. In addition,
      proteinase K-treated A. baumannii OMVs did not induce significant increase in
      expression of pro-inflammatory cytokine genes above the basal level, suggesting
      that the surface-exposed membrane proteins in intact OMVs are responsible for pro
      inflammatory response. Early inflammatory processes, such as vacuolization and
      detachment of epithelial cells and neutrophilic infiltration, were clearly
      observed in lungs of mice injected with A. baumannii OMVs. Our data demonstrate
      that OMVs produced by A. baumannii elicit a potent innate immune response, which
      may contribute to immunopathology of the infected host. 

PMID- 23977137
TI  - Comparative transcriptomic analysis of developing cotton cotyledons and embryo
      axis.
AB  - BACKGROUND: As a by product of higher value cotton fibre, cotton seed has been
      increasingly recognised to have excellent potential as a source of additional
      food, feed, biofuel stock and even a renewable platform for the production of
      many diverse biological molecules for agriculture and industrial enterprises. The
      large size difference between cotyledon and embryo axis that make up a cotton
      seed results in the under-representation of embryo axis gene transcript levels in
      whole seed embryo samples. Therefore, the determination of gene transcript levels
      in the cotyledons and embryo axes separately should lead to a better
      understanding of metabolism in these two developmentally diverse tissues.
      RESULTS: A comparative study of transcriptome changes between cotton developing
      cotyledon and embryo axis has been carried out. 17,384 unigenes (20.74% of all
      the unigenes) were differentially expressed in the two adjacent embryo tissues,
      and among them, 7,727 unigenes (44.45%) were down-regulated and 9,657 unigenes
      (55.55%) were up-regulated in cotyledon. CONCLUSIONS: Our study has provided a
      comprehensive dataset that documents the dynamics of the transcriptome at the mid
      maturity of cotton seed development and in discrete seed tissues, including
      embryo axis and cotyledon tissues. The results showed that cotton seed is subject
      to many transcriptome variations in these two tissue types and the differential
      gene expression between cotton embryo axis and cotyledon uncovered in our study
      should provide an important starting point for understanding how gene activity is
      coordinated during seed development to make a seed. Further, the identification
      of genes involved in rapid metabolite accumulation stage of seed development will
      extend our understanding of the complex molecular and cellular events in these
      developmental processes and provide a foundation for future studies on the
      metabolism, embryo differentiation of cotton and other dicot oilseed crops.

PMID- 23977138
TI  - Leukocyte activity is altered in a ground based murine model of microgravity and
      proton radiation exposure.
AB  - Immune system adaptation during spaceflight is a concern in space medicine.
      Decreased circulating leukocytes observed during and after space flight infer
      suppressed immune responses and susceptibility to infection. The microgravity
      aspect of the space environment has been simulated on Earth to study adverse
      biological effects in astronauts. In this report, the hindlimb unloading (HU)
      model was employed to investigate the combined effects of solar particle event
      like proton radiation and simulated microgravity on immune cell parameters
      including lymphocyte subtype populations and activity. Lymphocytes are a type of
      white blood cell critical for adaptive immune responses and T lymphocytes are
      regulators of cell-mediated immunity, controlling the entire immune response.
      Mice were suspended prior to and after proton radiation exposure (2 Gy dose) and
      total leukocyte numbers and splenic lymphocyte functionality were evaluated on
      days 4 or 21 after combined HU and radiation exposure. Total white blood cell
      (WBC), lymphocyte, neutrophil, and monocyte counts are reduced by approximately
      65%, 70%, 55%, and 70%, respectively, compared to the non-treated control group
      at 4 days after combined exposure. Splenic lymphocyte subpopulations are altered
      at both time points investigated. At 21 days post-exposure to combined HU and
      proton radiation, T cell activation and proliferation were assessed in isolated
      lymphocytes. Cell surface expression of the Early Activation Marker, CD69, is
      decreased by 30% in the combined treatment group, compared to the non-treated
      control group and cell proliferation was suppressed by approximately 50%,
      compared to the non-treated control group. These findings reveal that the
      combined stressors (HU and proton radiation exposure) result in decreased
      leukocyte numbers and function, which could contribute to immune system
      dysfunction in crew members. This investigation is one of the first to report on
      combined proton radiation and simulated microgravity effects on hematopoietic,
      specifically immune cells. 

PMID- 23977139
TI  - Down-regulation of c9orf86 in human breast cancer cells inhibits cell
      proliferation, invasion and tumor growth and correlates with survival of breast
      cancer patients.
AB  - C9orf86 which is a novel subfamily within the Ras superfamily of GTPases, is
      overexpressed in the majority of primary breast tumors. Few functional studies
      have focused on the C9orf86 protein; therefore, in this study, we explored the
      role of C9orf86 in breast carcinogenesis. In our study, we found that silencing
      of C9orf86 by siRNA in MCF-7 and SK-BR-3 cells resulted in suppressed cell
      proliferation as well as in vitro cell invasion capabilities. Moreover, knockdown
      of C9orf86 inhibited tumor growth in nude mice. Cell cycle and apoptotic assays
      showed that the anti-proliferative effect of C9orf86-siRNA was mediated by
      arresting cells in the G1 phase and promoting apoptosis. In addition, we found
      that patients with high levels of C9orf86 expression showed a significant trend
      towards worse survival compared to patients with low C9orf86 expression (P =
      0.002). These results provide evidence that C9orf86 represents a novel and
      clinically useful biomarker for BC patients and plays an important role during
      the progression of BC. 

PMID- 23977140
TI  - Differences in competitive ability between plants from nonnative and native
      populations of a tropical invader relates to adaptive responses in abiotic and
      biotic environments.
AB  - The evolution of competitive ability of invasive plant species is generally
      studied in the context of adaptive responses to novel biotic environments (enemy
      release) in introduced ranges. However, invasive plants may also respond to novel
      abiotic environments. Here we studied differences in competitive ability between
      Chromolaena odorata plants of populations from nonnative versus native ranges,
      considering biogeographical differences in both biotic and abiotic environments.
      An intraspecific competition experiment was conducted at two nutrient levels in a
      common garden. In both low and high nutrient treatments, C. odorata plants from
      nonnative ranges showed consistently lower root to shoot ratios than did plants
      from native ranges grown in both monoculture and competition. In the low nutrient
      treatment, C. odorata plants from nonnative ranges showed significantly lower
      competitive ability (competition-driven decreases in plant height and biomass
      were more), which was associated with their lower root to shoot ratios and higher
      total leaf phenolic content (defense trait). In the high nutrient treatment, C.
      odorata plants from nonnative ranges showed lower leaf toughness and cellulosic
      contents (defense traits) but similar competitive ability compared with plants
      from native ranges, which was also associated with their lower root to shoot
      ratios. Our results indicate that genetically based shifts in biomass allocation
      (responses to abiotic environments) also influence competitive abilities of
      invasive plants, and provide a first potential mechanism for the interaction
      between range and environment (environment-dependent difference between ranges). 

PMID- 23977141
TI  - Postgwas: advanced GWAS interpretation in R.
AB  - We present a comprehensive toolkit for post-processing, visualization and
      advanced analysis of GWAS results. In the spirit of comparable tools for gene
      expression analysis, we attempt to unify and simplify several procedures that are
      essential for the interpretation of GWAS results. This includes the generation of
      advanced Manhattan and regional association plots including rare variant display
      as well as novel interaction network analysis tools for the investigation of
      systems-biology aspects. Our package supports virtually all model organisms and
      represents the first cohesive implementation of such tools for the popular
      language R. Previous software of that range is dispersed over a wide range of
      platforms and mostly not adaptable for custom work pipelines. We demonstrate the
      utility of this package by providing an example workflow on a publicly available
      dataset. 

PMID- 23977142
TI  - Effective Alu repeat based RT-Qpcr normalization in cancer cell perturbation
      experiments.
AB  - BACKGROUND: Measuring messenger RNA (mRNA) levels using the reverse transcription
      quantitative polymerase chain reaction (RT-qPCR) is common practice in many
      laboratories. A specific set of mRNAs as internal control reference genes is
      considered as the preferred strategy to normalize RT-qPCR data. Proper selection
      of reference genes is a critical issue, especially in cancer cells that are
      subjected to different in vitro manipulations. These manipulations may result in
      dramatic alterations in gene expression levels, even of assumed reference genes.
      In this study, we evaluated the expression levels of 11 commonly used reference
      genes as internal controls for normalization of 19 experiments that include
      neuroblastoma, T-ALL, melanoma, breast cancer, non small cell lung cancer (NSCL),
      acute myeloid leukemia (AML), prostate cancer, colorectal cancer, and cervical
      cancer cell lines subjected to various perturbations. RESULTS: The geNorm
      algorithm in the software package qbase+ was used to rank the candidate reference
      genes according to their expression stability. We observed that the stability of
      most of the candidate reference genes varies greatly in perturbation experiments.
      Expressed Alu repeats show relatively stable expression regardless of
      experimental condition. These Alu repeats are ranked among the best reference
      assays in all perturbation experiments and display acceptable average expression
      stability values (M<0.5). CONCLUSIONS: We propose the use of Alu repeats as a
      reference assay when performing cancer cell perturbation experiments.

PMID- 23977143
TI  - Myocardial salvage is reduced in primary PCI-treated STEMI patients with
      microvascular obstruction, demonstrated by early and late CMR.
AB  - OBJECTIVES: This study evaluates the association between microvascular
      obstruction and myocardial salvage, determined by cardiac magnetic resonance
      performed both in the acute stage of myocardial infarction and after 4 months.
      METHODS: In patients with acute ST-elevation myocardial infarction treated by
      primary percutaneous coronary intervention, myocardial salvage, infarct size,
      left ventricular volumes, and ejection fraction were assessed by early (1-4 days)
      and follow-up (4 months) cardiac magnetic resonance. These variables were related
      to the presence or absence of microvascular obstruction at early investigation.
      Myocardial salvage was determined by: (1) myocardium at risk and infarct size
      measured in the acute stage and (2) myocardium at risk, measured acutely, and
      infarct size measured after 4 months. Multivariate analyses were performed,
      adjusting for clinical confounders at baseline. RESULTS: Microvascular
      obstruction was present in 49 of 94 included patients, (52%). Myocardial salvage
      was significantly reduced in patients with microvascular obstruction, compared to
      those without: 23% vs. 38%, measured acutely, and 39.8% vs. 65.4%, after 4 months
      (p<0.001). The presence of microvascular obstruction was significantly and
      independently associated with large infarct size, lower left ventricular ejection
      fraction, and larger left ventricular end-systolic volume. CONCLUSION: The
      presence of microvascular obstruction demonstrated by cardiac magnetic resonance
      early after infarction was associated with impaired myocardial salvage. This
      association was more marked when based on measurement of infarct size after 4
      months compared to assessment in the acute stage.

PMID- 23977144
TI  - Creating larger and better connected protected areas enhances the persistence of
      big game species in the maputaland-pondoland-albany biodiversity hotspot.
AB  - The ideal conservation planning approach would enable decision-makers to use
      population viability analysis to assess the effects of management strategies and
      threats on all species at the landscape level. However, the lack of high-quality
      data derived from long-term studies, and uncertainty in model parameters and/or
      structure, often limit the use of population models to only a few species of
      conservation concern. We used spatially explicit metapopulation models in
      conjunction with multi-criteria decision analysis to assess how species-specific
      threats and management interventions would affect the persistence of African wild
      dog, black rhino, cheetah, elephant, leopard and lion, under six reserve
      scenarios, thereby providing the basis for deciding on a best course of
      conservation action in the South African province of KwaZulu-Natal, which forms
      the central component of the Maputaland-Pondoland-Albany biodiversity hotspot.
      Overall, the results suggest that current strategies of managing populations
      within individual, small, fenced reserves are unlikely to enhance metapopulation
      persistence should catastrophic events affect populations in the future. Creating
      larger and better-connected protected areas would ensure that threats can be
      better mitigated in the future for both African wild dog and leopard, which can
      disperse naturally, and black rhino, cheetah, elephant, and lion, which are
      constrained by electric fences but can be managed using translocation. The
      importance of both size and connectivity should inform endangered megafauna
      conservation and management, especially in the context of restoration efforts in
      increasingly human-dominated landscapes. 

PMID- 23977145
TI  - Increased risk of acute pancreatitis in patients with chronic hemodialysis: a 4
      year follow-up study.
AB  - BACKGROUND: The risk of acute pancreatitis in patients on long-term peritoneal
      dialysis is higher as compared to the general population. However, the
      relationship between long-term hemodialysis and acute pancreatitis has never been
      established. OBJECTIVES: We investigated the incidence of acute pancreatitis
      among patients on long-term hemodialysis in Taiwan to evaluate if there is a
      higher risk of acute pancreatitis in comparison to the general population.
      METHODS: We utilized a National Health Insurance (NHI) claims data sample
      containing one million beneficiaries. We followed all adult beneficiaries from
      January 1, 2007 until December 31, 2010 to see if they had been hospitalized for
      acute pancreatitis during this period. We further identified patients on chronic
      hemodialysis and compared their risk of acute pancreatitis with the general
      population. RESULTS: This study included 2603 patients with long-term
      hemodialysis and 773,140 patients without hemodialysis. After controlling for
      age, gender, Charlson Comorbidity Index Score, geographic region, socioeconomic
      status and urbanization level, the adjusted hazard ratio was 3.44 (95% Confidence
      interval, 2.5-4.7). CONCLUSIONS: The risk of acute pancreatitis in patients on
      long-term hemodialysis is significantly higher in comparison to the general
      population.

PMID- 23977146
TI  - Improving the performance of outbreak detection algorithms by classifying the
      levels of disease incidence.
AB  - We evaluated a novel strategy to improve the performance of outbreak detection
      algorithms, namely setting the alerting threshold separately in each region
      according to the disease incidence in that region. By using data on hand, foot
      and mouth disease in Shandong province, China, we evaluated the impact of disease
      incidence on the performance of outbreak detection algorithms (EARS-C1, C2 and
      C3). Compared to applying the same algorithm and threshold to the whole region,
      setting the optimal threshold in each region according to the level of disease
      incidence (i.e., high, middle, and low) enhanced sensitivity (C1: from 94.4% to
      99.1%, C2: from 93.5% to 95.4%, C3: from 91.7% to 95.4%) and reduced the number
      of alert signals (the percentage of reduction is C1?4.3%, C2?11.9%, C3?10.3%).
      Our findings illustrate a general method for improving the accuracy of detection
      algorithms that is potentially applicable broadly to other diseases and regions. 

PMID- 23977147
TI  - Fungi of the murine gut: episodic variation and proliferation during antibiotic
      treatment.
AB  - Antibiotic use in humans has been associated with outgrowth of fungi. Here we
      used a murine model to investigate the gut microbiome over 76 days of treatment
      with vancomycin, ampicillin, neomycin, and metronidazole and subsequent recovery.
      Mouse stool was studied as a surrogate for the microbiota of the lower
      gastrointestinal tract. The abundance of fungi and bacteria was measured using
      quantitative PCR, and the proportional composition of the communities quantified
      using 454/Roche pyrosequencing of rRNA gene tags. Prior to treatment, bacteria
      outnumbered fungi by >3 orders of magnitude. Upon antibiotic treatment, bacteria
      dropped in abundance >3 orders of magnitude, so that the predominant 16S
      sequences detected became transients derived from food. Upon cessation of
      treatment, bacterial communities mostly returned to their previous numbers and
      types after 8 weeks, though communities remained detectably different from
      untreated controls. Fungal communities varied substantially over time, even in
      the untreated controls. Separate cages within the same treatment group showed
      radical differences, but mice within a cage generally behaved similarly. Fungi
      increased ~40-fold in abundance upon antibiotic treatment but declined back to
      their original abundance after cessation of treatment. At the last time point,
      Candida remained more abundant than prior to treatment. These data show that 1)
      gut fungal populations change radically during normal mouse husbandry, 2) fungi
      grow out in the gut upon suppression of bacterial communities with antibiotics,
      and 3) perturbations due to antibiotics persist long term in both the fungal and
      bacterial microbiota. 

PMID- 23977148
TI  - Towards an elastographic atlas of brain anatomy.
AB  - Cerebral viscoelastic constants can be measured in a noninvasive, image-based way
      by magnetic resonance elastography (MRE) for the detection of neurological
      disorders. However, MRE brain maps of viscoelastic constants are still limited by
      low spatial resolution. Here we introduce three-dimensional multifrequency MRE of
      the brain combined with a novel reconstruction algorithm based on a model-free
      multifrequency inversion for calculating spatially resolved viscoelastic
      parameter maps of the human brain corresponding to the dynamic range of shear
      oscillations between 30 and 60 Hz. Maps of two viscoelastic parameters, the
      magnitude and the phase angle of the complex shear modulus, |G*| and phi, were
      obtained and normalized to group templates of 23 healthy volunteers in the age
      range of 22 to 72 years. This atlas of the anatomy of brain mechanics reveals a
      significant contrast in the stiffness parameter |G*| between different anatomical
      regions such as white matter (WM; 1.252+/-0.260 kPa), the corpus callosum genu
      (CCG; 1.104+/-0.280 kPa), the thalamus (TH; 1.058+/-0.208 kPa) and the head of
      the caudate nucleus (HCN; 0.649+/-0.101 kPa). phi, which is sensitive to the
      lossy behavior of the tissue, was in the order of CCG (1.011+/-0.172), TH
      (1.037+/-0.173), CN (0.906+/-0.257) and WM (0.854+/-0.169). The proposed method
      provides the first normalized maps of brain viscoelasticity with anatomical
      details in subcortical regions and provides useful background data for clinical
      applications of cerebral MRE. 

PMID- 23977149
TI  - VEGF receptor blockade markedly reduces retinal microglia/macrophage infiltration
      into laser-induced CNV.
AB  - Although blocking VEGF has a positive effect in wet age-related macular
      degeneration (AMD), the effect of blocking its receptors remains unclear. This
      was an investigation of the effect of VEGF receptor (VEGFR) 1 and/or 2 blockade
      on retinal microglia/macrophage infiltration in laser-induced choroidal
      neovascularization (CNV), a model of wet AMD. CNV lesions were isolated by laser
      capture microdissection at 3, 7, and 14 days after laser and analyzed by RT-PCR
      and immunofluorescence staining for mRNA and protein expression, respectively.
      Neutralizing antibodies for VEGFR1 or R2 and the microglia inhibitor minocycline
      were injected intraperitoneally (IP). Anti-CD11b, CD45 and Iba1 antibodies were
      used to confirm the cell identity of retinal microglia/macrophage, in the
      RPE/choroidal flat mounts or retinal cross sections. CD11b(+), CD45(+) or Iba1(+)
      cells were counted. mRNA of VEGFR1 and its three ligands, PlGF, VEGF-A (VEGF) and
      VEGF-B, were expressed at all stages, but VEGFR2 were detected only in the late
      stage. PlGF and VEGF proteins were expressed at 3 and 7 days after laser. Anti
      VEGFR1 (MF1) delivered IP 3 days after laser inhibited infiltration of leukocyte
      populations, largely retinal microglia/macrophage to CNV, while anti-VEGFR2
      (DC101) had no effect. At 14 days after laser, both MF1 and DC101 antibodies
      markedly inhibited retinal microglia/macrophage infiltration into CNV. Therefore,
      VEGFR1 and R2 play differential roles in the pathogenesis of CNV: VEGFR1 plays a
      dominant role at 3 days after laser; but both receptors play pivotal roles at 14
      days after laser. In vivo imaging demonstrated accumulation of GFP-expressing
      microglia into CNV in both CX3CR1(gfp/gfp) and CX3CR1(gfp/+) mice. Minocycline
      treatment caused a significant increase in lectin(+) cells in the sub-retinal
      space anterior to CNV and a decrease in dextran-perfused neovessels compared to
      controls. Targeting the chemoattractant molecules that regulate trafficking of
      retinal microglia/macrophage appears to be a compelling therapeutic strategy to
      control CNV and treat wet AMD. 

PMID- 23977150
TI  - Effects of KCNQ2 gene truncation on M-type Kv7 potassium currents.
AB  - The KCNQ2 gene product, Kv7.2, is a subunit of the M-channel, a low-threshold
      voltage-gated K(+) channel that regulates mammalian and human neuronal
      excitability. Spontaneous mutations one of the KCNQ2 genes cause disorders of
      neural excitability such as Benign Familial Neonatal Seizures. However there
      appear to be no reports in which both human KCNQ2 genes are mutated. We therefore
      asked what happens to M-channel function when both KCNQ2 genes are disrupted. We
      addressed this using sympathetic neurons isolated from mice in which the KCNQ2
      gene was truncated at a position corresponding to the second transmembrane domain
      of the Kv7.2 protein. Since homozygote KCNQ2-/- mice die postnatally, experiments
      were largely restricted to neurons from late embryos. Quantitative PCR revealed
      an absence of KCNQ2 mRNA in ganglia from KCNQ2-/- embryos but 100-120% increase
      of KCNQ3 and KCNQ5 mRNAs; KCNQ2+/- ganglia showed ~30% less KCNQ2 mRNA than wild
      type (+/+) ganglia but 40-50% more KCNQ3 and KCNQ5 mRNA. Neurons from KCNQ2-/-
      embryos showed a complete absence of M-current, even after applying the Kv7
      channel enhancer, retigabine. Neurons from heterozygote KCNQ2+/- embryos had ~60%
      reduced M-current. In contrast, M-currents in neurons from adult KCNQ2+/- mice
      were no smaller than those in neurons from wild-type mice. Measurements of
      tetraethylammonium block did not indicate an increased expression of Kv7.5
      containing subunits, implying a compensatory increase in Kv7.2 expression from
      the remaining KCNQ2 gene. We conclude that mouse embryonic M-channels have an
      absolute requirement for Kv7.2 subunits for functionality, that the reduced M
      channel activity in heterozygote KCNQ2+/- mouse embryos results primarily from a
      gene-dosage effect, and that there is a compensatory increase in Kv7.2 expression
      in adult mice. 

PMID- 23977151
TI  - Comparison of pooled risk estimates for adverse effects from different
      observational study designs: methodological overview.
AB  - BACKGROUND: A diverse range of study designs (e.g. case-control or cohort) are
      used in the evaluation of adverse effects. We aimed to ascertain whether the risk
      estimates from meta-analyses of case-control studies differ from that of other
      study designs. METHODS: Searches were carried out in 10 databases in addition to
      reference checking, contacting experts, and handsearching key journals and
      conference proceedings. Studies were included where a pooled relative measure of
      an adverse effect (odds ratio or risk ratio) from case-control studies could be
      directly compared with the pooled estimate for the same adverse effect arising
      from other types of observational studies. RESULTS: We included 82 meta-analyses.
      Pooled estimates of harm from the different study designs had 95% confidence
      intervals that overlapped in 78/82 instances (95%). Of the 23 cases of discrepant
      findings (significant harm identified in meta-analysis of one type of study
      design, but not with the other study design), 16 (70%) stemmed from significantly
      elevated pooled estimates from case-control studies. There was associated
      evidence of funnel plot asymmetry consistent with higher risk estimates from case
      control studies. On average, cohort or cross-sectional studies yielded pooled
      odds ratios 0.94 (95% CI 0.88-1.00) times lower than that from case-control
      studies. INTERPRETATION: Empirical evidence from this overview indicates that
      meta-analysis of case-control studies tend to give slightly higher estimates of
      harm as compared to meta-analyses of other observational studies. However it is
      impossible to rule out potential confounding from differences in drug dose,
      duration and populations when comparing between study designs.

PMID- 23977152
TI  - Down-regulation of SIX3 is associated with clinical outcome in lung
      adenocarcinoma.
AB  - BACKGROUND: Lung cancer is a common cancer and the leading cause of cancer
      related death worldwide. SIX3 is a human homologue of the highly conserved sine
      oculis gene family essential during embryonic development in vertebrates, and
      encodes a homeo-domain containing transcription factor. Little is known about the
      role of SIX3 in human tumorigenesis. This study is to assess the
      expression/function of SIX3 and the significance of SIX3 as a prognostic
      biomarker in lung adenocarcinoma. METHODS: Quantitative real-time RT-PCR was used
      to analyze SIX3 mRNA expression and quantitative methylation specific PCR (MSP)
      was used to examine promoter methylation. MTS and colony formation assays were
      performed to examine cell proliferation. Wound healing assays were used to assess
      cell migration, and microarrays were utilized to examine genes regulated by SIX3
      in lung cancer cells. Association of SIX3 expression levels with clinical
      outcomes of patients with lung adenocarcinoma was evaluated using the Kaplan
      Meier method and a multivariate Cox proportional hazards regression model.
      RESULTS: SIX3 was down-regulated in lung adenocarcinoma tissues compared to their
      matched adjacent normal tissues, and this down-regulation was associated with
      methylation of the SIX3 promoter. SIX3 was also methylation-silenced in lung
      cancer cell lines. Restoration of SIX3 in lung cancer cells lacking endogenous
      SIX3 suppressed cell proliferation and migration, and downregulated a number of
      genes involved in proliferation and metastasis such as S100P, TGFB3, GINS3 and
      BAG1. Moreover, SIX3 mRNA expression was associated with significantly improved
      overall survival (OS) and progression-free survival (PFS) in adenocarcinoma
      patients and patients with bronchioloalveolar carcinoma (BAC) features.
      CONCLUSIONS: SIX3 may play an important role as a novel suppressor in human lung
      cancer. SIX3 has potential as a novel prognostic biomarker for patients with lung
      adenocarcinomas.

PMID- 23977153
TI  - The expected number of background disease events during mass immunization in
      China.
AB  - It is critical to distinguish events that are temporarily associated with, but
      not caused by, vaccination from those caused by vaccination during mass
      immunization. We performed a literature search in China National Knowledge
      Infrastructure and Pubmed databases. The number of coincident events was
      calculated based on its incidence rate and periods after receipt of a dose of
      hypothesized vaccine. We included background incidences of Guillain-Barre
      syndrome, anaphylaxis, seizure, sudden adult death syndrome, sudden cardiac
      death, spontaneous abortion, and preterm labour or delivery. In a cohort of 10
      million individuals, 7.71 cases of Guillain-Barre syndrome would be expected to
      occur within six weeks of vaccination as coincident background cases. Even for
      rare events, a large number of events can be expected in a short period because
      of the large population targeted for immunization. These findings may encourage
      health authorities to screen the safety of vaccines against unpredictable
      pathogens. 

PMID- 23977154
TI  - DTW4Omics: comparing patterns in biological time series.
AB  - When studying time courses of biological measurements and comparing these to
      other measurements eg. gene expression and phenotypic endpoints, the analysis is
      complicated by the fact that although the associated elements may show the same
      patterns of behaviour, the changes do not occur simultaneously. In these cases
      standard correlation-based measures of similarity will fail to find significant
      associations. Dynamic time warping (DTW) is a technique which can be used in
      these situations to find the optimal match between two time courses, which may
      then be assessed for its significance. We implement DTW4Omics, a tool for
      performing DTW in R. This tool extends existing R scripts for DTW making them
      applicable for "omics" datasets where thousands entities may need to be compared
      with a range of markers and endpoints. It includes facilities to estimate the
      significance of the matches between the supplied data, and provides a set of
      plots to enable the user to easily visualise the output. We illustrate the
      utility of this approach using a dataset linking the exposure of the colon
      carcinoma Caco-2 cell line to oxidative stress by hydrogen peroxide (H2O2) and
      menadione across 9 timepoints and show that on average 85% of the genes found are
      not obtained from a standard correlation analysis between the genes and the
      measured phenotypic endpoints. We then show that when we analyse the genes
      identified by DTW4Omics as significantly associated with a marker for oxidative
      DNA damage (8-oxodG), through over-representation, an Oxidative Stress pathway is
      identified as the most over-represented pathway demonstrating that the genes
      found by DTW4Omics are biologically relevant. In contrast, when the positively
      correlated genes were similarly analysed, no pathways were found. The tool is
      implemented as an R Package and is available, along with a user guide from
      http://web.tgx.unimaas.nl/svn/public/dtw/. 

PMID- 23977155
TI  - Implicit trust between the Uyghur and the Han in Xinjiang, China.
AB  - Trust is a vital lubricant that increases the sense of security in social
      interactions. In this study, we investigated the intergroup trust between the
      Uyghur and the Han, the two largest ethnic groups in Xinjiang, China, with a
      Go/No-Go Association Task. Specifically, we instructed Uyghur and Han
      participants to respond to ethnic faces (Uyghur vs. Han) and trust/distrust words
      and measured the strength of the automatic associations between the faces and
      words for both in-group and out-group pairs. As expected, both ethnic groups
      showed implicit in-group trust and out-group distrust, but the Han group
      demonstrated stronger in-group trust and out-group distrust toward the Uyghur
      than the Uyghur group toward the Han. However, the magnitude of distrust of the
      Han toward the Uyghur was small to medium as compared with that reported by other
      intergroup relationship research. In addition, participant geographic location
      was associated with out-group distrust. These findings offer implications for
      developing effective strategies to encourage trust between conflicting groups. 

PMID- 23977157
TI  - Find duplicates among the PubMed, EMBASE, and Cochrane Library Databases in
      systematic review.
AB  - BACKGROUND: Finding duplicates is an important phase of systematic review.
      However, no consensus regarding the methods to find duplicates has been provided.
      This study aims to describe a pragmatic strategy of combining auto- and hand
      searching duplicates in systematic review and to evaluate the prevalence and
      characteristics of duplicates. METHODS AND FINDINGS: Literatures regarding portal
      vein thrombosis (PVT) and Budd-Chiari syndrome (BCS) were searched by the PubMed,
      EMBASE, and Cochrane library databases. Duplicates included one index paper and
      one or more redundant papers. They were divided into type-I (duplicates among
      different databases) and type-II (duplicate publications in different
      journals/issues) duplicates. For type-I duplicates, reference items were further
      compared between index and redundant papers. Of 10936 papers regarding PVT, 2399
      and 1307 were identified as auto- and hand-searched duplicates, respectively. The
      prevalence of auto- and hand-searched redundant papers was 11.0% (1201/10936) and
      6.1% (665/10936), respectively. They included 3431 type-I and 275 type-II
      duplicates. Of 11403 papers regarding BCS, 3275 and 2064 were identified as auto-
      and hand-searched duplicates, respectively. The prevalence of auto- and hand
      searched redundant papers was 14.4% (1640/11403) and 9.1% (1039/11403),
      respectively. They included 5053 type-I and 286 type-II duplicates. Most of type
      I duplicates were identified by auto-searching method (69.5%, 2385/3431 in PVT
      literatures; 64.6%, 3263/5053 in BCS literatures). Nearly all type-II duplicates
      were identified by hand-searching method (94.9%, 261/275 in PVT literatures;
      95.8%, 274/286 in BCS literatures). Compared with those identified by auto
      searching method, type-I duplicates identified by hand-searching method had a
      significantly higher prevalence of wrong items (47/2385 versus 498/1046, p<0.0001
      in PVT literatures; 30/3263 versus 778/1790, p<0.0001 in BCS literatures). Most
      of wrong items originated from EMBASE database. CONCLUSION: Given the inadequacy
      of a single strategy of auto-searching method, a combined strategy of auto- and
      hand-searching methods should be employed to find duplicates in systematic
      review.

PMID- 23977156
TI  - Functional mapping of human dynamin-1-like GTPase domain based on x-ray structure
      analyses.
AB  - Human dynamin-1-like protein (DNM1L) is a GTP-driven molecular machine that
      segregates mitochondria and peroxisomes. To obtain insights into its catalytic
      mechanism, we determined crystal structures of a construct comprising the GTPase
      domain and the bundle signaling element (BSE) in the nucleotide-free and GTP
      analogue-bound states. The GTPase domain of DNM1L is structurally related to that
      of dynamin and binds the nucleotide 5'-Guanylyl-imidodiphosphate (GMP-PNP) via
      five highly conserved motifs, whereas the BSE folds into a pocket at the opposite
      side. Based on these structures, the GTPase center was systematically mapped by
      alanine mutagenesis and kinetic measurements. Thus, residues essential for the
      GTPase reaction were characterized, among them Lys38, Ser39 and Ser40 in the
      phosphate binding loop, Thr59 from switch I, Asp146 and Gly149 from switch II,
      Lys216 and Asp218 in the G4 element, as well as Asn246 in the G5 element. Also,
      mutated Glu81 and Glu82 in the unique 16-residue insertion of DNM1L influence the
      activity significantly. Mutations of Gln34, Ser35, and Asp190 in the predicted
      assembly interface interfered with dimerization of the GTPase domain induced by a
      transition state analogue and led to a loss of the lipid-stimulated GTPase
      activity. Our data point to related catalytic mechanisms of DNM1L and dynamin
      involving dimerization of their GTPase domains. 

PMID- 23977158
TI  - iNOS-dependent increase in colonic mucus thickness in DSS-colitic rats.
AB  - AIM: To investigate colonic mucus thickness in vivo in health and during
      experimental inflammatory bowel disease. METHODS: Colitis was induced with 5% DSS
      in drinking water for 8 days prior to experiment, when the descending colonic
      mucosa of anesthetized rats was studied using intravital microscopy. Mucus
      thickness was measured with micropipettes attached to a micromanipulator. To
      assess the contributions of NOS and prostaglandins in the regulation of colonic
      mucus thickness, the non-selective NOS-inhibitor L-NNA (10 mg/kg bolus followed
      by 3 mg/kg/h), the selective iNOS-inhibitor L-NIL (10 mg/kg bolus followed by 3
      mg/kg/h) and the non-selective COX-inhibitor diclofenac (5 mg/kg) were
      administered intravenously prior to experiment. To further investigate the role
      of iNOS in the regulation of colonic mucus thickness, iNOS -/- mice were used.
      RESULTS: Colitic rats had a thicker firmly adherent mucus layer following 8 days
      of DSS treatment than untreated rats (88+/-2 um vs 76+/-1 um). During induction
      of colitis, the thickness of the colonic mucus layer initially decreased but was
      from day 3 significantly thicker than in untreated rats. Diclofenac reduced the
      mucus thickness similarly in colitic and untreated rats (-16+/-5 um vs -14+/-2
      um). While L-NNA had no effect on colonic mucus thickness in DSS or untreated
      controls (+3+/-2 um vs +3+/-1 um), L-NIL reduced the mucus thickness
      significantly more in colitic rats than in controls (-33+/-4 um vs -10+/-3 um).
      The importance of iNOS in regulating the colonic mucus thickness was confirmed in
      iNOS-/- mice, which had thinner colonic mucus than wild-type mice (35+/-3 um vs
      50+/-2 um, respectively). Furthermore, immunohistochemistry revealed increased
      levels of iNOS in the colonic surface epithelium following DSS treatment.
      CONCLUSION: Both prostaglandins and nitric oxide regulate basal colonic mucus
      thickness. During onset of colitis, the thickness of the mucus layer is initially
      reduced followed by an iNOS mediated increase.

PMID- 23977159
TI  - Mother to offspring transmission of chronic wasting disease in reeves' muntjac
      deer.
AB  - The horizontal transmission of prion diseases has been well characterized in
      bovine spongiform encephalopathy (BSE), chronic wasting disease (CWD) of deer and
      elk and scrapie of sheep, and has been regarded as the primary mode of
      transmission. Few studies have monitored the possibility of vertical transmission
      occurring within an infected mother during pregnancy. To study the potential for
      and pathway of vertical transmission of CWD in the native cervid species, we used
      a small cervid model-the polyestrous breeding, indoor maintainable, Reeves'
      muntjac deer-and determined that the susceptibility and pathogenesis of CWD in
      these deer reproduce that in native mule and white-tailed deer. Moreover, we
      demonstrate here that CWD prions are transmitted from doe to fawn. Maternal CWD
      infection also appears to result in lower percentage of live birth offspring. In
      addition, evolving evidence from protein misfolding cyclic amplification (PMCA)
      assays on fetal tissues suggest that covert prion infection occurs in utero.
      Overall, our findings demonstrate that transmission of prions from mother to
      offspring can occur, and may be underestimated for all prion diseases. 

PMID- 23977160
TI  - Hyperlipidemia impaired innate immune response to periodontal pathogen
      porphyromonas gingivalis in apolipoprotein E knockout mice.
AB  - A finely-tuned innate immune response plays a pivotal role in protecting host
      against bacterial invasion during periodontal disease progression. Hyperlipidemia
      has been suggested to exacerbate periodontal health condition. However, the
      underlying mechanism has not been addressed. In the present study, we
      investigated the effect of hyperlipidemia on innate immune responses to
      periodontal pathogen Porphyromonas gingivalis infection. Apolipoprotein E
      deficient and wild-type mice at the age of 20 weeks were used for the study.
      Peritoneal macrophages were isolated and subsequently used for the study of
      viable P. gingivalis infection. ApoE(-/-) mice demonstrated inhibited iNOS
      production and impaired clearance of P. gingivalis in vitro and in vivo;
      furthermore, ApoE(-/-) mice displayed disrupted cytokine production pattern in
      response to P. gingivalis, with a decreased production of tumor necrosis factor
      alpha, interleukin-6 (IL-6), IL-1beta and monocyte chemotactic protein-1.
      Microarray data demonstrated that Toll-like receptor (TLR) and NOD-like receptor
      (NLR) pathway were altered in ApoE(-/-) mice macrophages; further analysis of
      pattern recognition receptors (PRRs) demonstrated that expression of triggering
      receptors on myeloid cells-1 (TREM-1), an amplifier of the TLR and NLR pathway,
      was decreased in ApoE(-/-) mice macrophages, leading to decreased recruitment of
      NF-kappaB onto the promoters of the TNF-alpha and IL-6. Our data suggest that in
      ApoE(-/-) mice hyperlipidemia disrupts the expression of PRRs, and cripples the
      host's capability to generate sufficient innate immune response to P. gingivalis,
      which may facilitate immune evasion, subgingival colonization and establishment
      of P. gingivalis in the periodontal niche. 

PMID- 23977161
TI  - Mutations in LMNA modulate the lamin A--Nesprin-2 interaction and cause LINC
      complex alterations.
AB  - BACKGROUND: In eukaryotes the genetic material is enclosed by a continuous
      membrane system, the nuclear envelope (NE). Along the NE specific proteins
      assemble to form meshworks and mutations in these proteins have been described in
      a group of human diseases called laminopathies. Laminopathies include
      lipodystrophies, muscle and cardiac diseases as well as metabolic or progeroid
      syndromes. Most laminopathies are caused by mutations in the LMNAgene encoding
      lamins A/C. Together with Nesprins (Nuclear Envelope Spectrin Repeat Proteins)
      they are core components of the LINC complex (Linker of Nucleoskeleton and
      Cytoskeleton). The LINC complex connects the nucleoskeleton and the cytoskeleton
      and plays a role in the transfer of mechanically induced signals along the NE
      into the nucleus, and its components have been attributed functions in
      maintaining nuclear and cellular organization as well as signal transduction.
      RESULTS: Here we narrowed down the interaction sites between lamin A and Nesprin
      2 to aa 403-425 in lamin A and aa 6146-6347 in Nesprin-2. Laminopathic mutations
      in and around the involved region of lamin A (R401C, G411D, G413C, V415I, R419C,
      L421P, R427G, Q432X) modulate the interaction with Nesprin-2 and this may
      contribute to the disease phenotype. The most notable mutation is the lamin A
      mutation Q432X that alters LINC complex protein assemblies and causes chromosomal
      and transcription factor rearrangements. CONCLUSION: Mutations in Nesprin-2 and
      lamin A are characterised by complex genotype phenotype relations. Our data show
      that each mutation in LMNAanalysed here has a distinct impact on the interaction
      among both proteins that substantially explains how distinct mutations in widely
      expressed genes lead to the formation of phenotypically different diseases.

PMID- 23977162
TI  - Accurate detection and quantification of the fish viral hemorrhagic Septicemia
      virus (VHSv) with a two-color fluorometric real-time PCR assay.
AB  - Viral Hemorrhagic Septicemia virus (VHSv) is one of the world's most serious fish
      pathogens, infecting >80 marine, freshwater, and estuarine fish species from
      Eurasia and North America. A novel and especially virulent strain - IVb -
      appeared in the Great Lakes in 2003, has killed many game fish species in a
      series of outbreaks in subsequent years, and shut down interstate transport of
      baitfish. Cell culture is the diagnostic method approved by the USDA-APHIS, which
      takes a month or longer, lacks sensitivity, and does not quantify the amount of
      virus. We thus present a novel, easy, rapid, and highly sensitive real-time
      quantitative reverse transcription PCR (qRT-PCR) assay that incorporates
      synthetic competitive template internal standards for quality control to
      circumvent false negative results. Results demonstrate high signal-to-analyte
      response (slope = 1.00+/-0.02) and a linear dynamic range that spans seven orders
      of magnitude (R(2) = 0.99), ranging from 6 to 6,000,000 molecules. Infected
      fishes are found to harbor levels of virus that range to 1,200,000 VHSv
      molecules/10(6) actb1 molecules with 1,000 being a rough cut-off for clinical
      signs of disease. This new assay is rapid, inexpensive, and has significantly
      greater accuracy than other published qRT-PCR tests and traditional cell culture
      diagnostics. 

PMID- 23977163
TI  - The influence of minimum sitting period of the ActivPALTM on the measurement of
      breaks in sitting in young children.
AB  - BACKGROUND: Sitting time and breaks in sitting influence cardio-metabolic health.
      New monitors (e.g. activPALTM) may be more accurate for measurement of sitting
      time and breaks in sitting although how to optimize measurement accuracy is not
      yet clear. One important issue is the minimum sitting/upright period (MSUP) to
      define a new posture. Using the activPALTM, we investigated the effect of
      variations in MSUP on total sitting time and breaks in sitting, and also
      determined the criterion validity of different activPALTM settings for both
      constructs. METHODS: We varied setting of MSUP in 23 children (mean (SD) age 4.5
      y (0.7)) who wore activPALTM (24 hr/d) for 5-7 d. We first studied activPALTM
      using the default setting of 10 s MSUP and then reduced this to 5 s, 2 s and 1 s.
      In a second study, in a convenience sample of 30 pre-school children (mean age
      4.1 y (SD 0.5)) we validated the activPALTM measures of sitting time and breaks
      in sitting at different MSUP settings against direct observation. RESULTS:
      Comparing settings of 10, 5, 2 and 1 s, there were no significant differences in
      sitting time (6.2 hr (1.0), 6.3 hr (1.0), 6.4 hr (1.0) and 6.3 hr (1.6),
      respectively) between settings but there were significant increases in the
      apparent number of breaks - (8(3), 14(2), 21(4) and 28 (6)/h) at 10, 5, 2 and 1 s
      settings, respectively. In comparison with direct observation, a 2 s setting had
      the smallest error relative to direct observation (95% limits of agreement: -14
      to +17 sitting bouts/hr, mean difference 1.83, p = 0.2). CONCLUSION: With
      activPALTM, breaks in sitting, but not total sitting time, are highly sensitive
      to the setting of MSUP, with 2 s optimal for young children. The MSUP to define a
      new posture will need to be empirically determined if accurate measurements of
      number of breaks in sitting are to be obtained.

PMID- 23977164
TI  - Engrafted human induced pluripotent stem cell-derived anterior specified neural
      progenitors protect the rat crushed optic nerve.
AB  - BACKGROUND: Degeneration of retinal ganglion cells (RGCs) is a common occurrence
      in several eye diseases. This study examined the functional improvement and
      protection of host RGCs in addition to the survival, integration and neuronal
      differentiation capabilities of anterior specified neural progenitors (NPs)
      following intravitreal transplantation. METHODOLOGY/PRINCIPAL FINDINGS: NPs were
      produced under defined conditions from human induced pluripotent stem cells
      (hiPSCs) and transplanted into rats whose optic nerves have been crushed (ONC).
      hiPSCs were induced to differentiate into anterior specified NPs by the use of
      Noggin and retinoic acid. The hiPSC-NPs were labeled by green fluorescent protein
      or a fluorescent tracer 1,1' -dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine
      perchlorate (DiI) and injected two days after induction of ONC in hooded rats.
      Functional analysis according to visual evoked potential recordings showed
      significant amplitude recovery in animals transplanted with hiPSC-NPs. Retrograde
      labeling by an intra-collicular DiI injection showed significantly higher numbers
      of RGCs and spared axons in ONC rats treated with hiPSC-NPs or their conditioned
      medium (CM). The analysis of CM of hiPSC-NPs showed the secretion of ciliary
      neurotrophic factor, basic fibroblast growth factor, and insulin-like growth
      factor. Optic nerve of cell transplanted groups also had increased GAP43
      immunoreactivity and myelin staining by FluoroMyelinTM which imply for protection
      of axons and myelin. At 60 days post-transplantation hiPSC-NPs were integrated
      into the ganglion cell layer of the retina and expressed neuronal markers.
      CONCLUSIONS/SIGNIFICANCE: The transplantation of anterior specified NPs may
      improve optic nerve injury through neuroprotection and differentiation into
      neuronal lineages. These NPs possibly provide a promising new therapeutic
      approach for traumatic optic nerve injuries and loss of RGCs caused by other
      diseases.

PMID- 23977165
TI  - Octarellin VI: using rosetta to design a putative artificial (beta/alpha)8
      protein.
AB  - The computational protein design protocol Rosetta has been applied successfully
      to a wide variety of protein engineering problems. Here the aim was to test its
      ability to design de novo a protein adopting the TIM-barrel fold, whose formation
      requires about twice as many residues as in the largest proteins successfully
      designed de novo to date. The designed protein, Octarellin VI, contains 216
      residues. Its amino acid composition is similar to that of natural TIM-barrel
      proteins. When produced and purified, it showed a far-UV circular dichroism
      spectrum characteristic of folded proteins, with alpha-helical and beta-sheet
      secondary structure. Its stable tertiary structure was confirmed by both
      tryptophan fluorescence and circular dichroism in the near UV. It proved heat
      stable up to 70 degrees C. Dynamic light scattering experiments revealed a unique
      population of particles averaging 4 nm in diameter, in good agreement with our
      model. Although these data suggest the successful creation of an artificial
      alpha/beta protein of more than 200 amino acids, Octarellin VI shows an apparent
      noncooperative chemical unfolding and low solubility. 

PMID- 23977166
TI  - Comparative proteomics reveals novel components at the plasma membrane of
      differentiated HepaRG cells and different distribution in hepatocyte- and biliary
      like cells.
AB  - Hepatitis B virus (HBV) is a human pathogen causing severe liver disease and
      eventually death. Despite important progress in deciphering HBV internalization,
      the early virus-cell interactions leading to infection are not known. HepaRG is a
      human bipotent liver cell line bearing the unique ability to differentiate
      towards a mixture of hepatocyte- and biliary-like cells. In addition to
      expressing metabolic functions normally found in liver, differentiated HepaRG
      cells support HBV infection in vitro, thus resembling cultured primary
      hepatocytes more than other hepatoma cells. Therefore, extensive characterization
      of the plasma membrane proteome from HepaRG cells would allow the identification
      of new cellular factors potentially involved in infection. Here we analyzed the
      plasma membranes of non-differentiated and differentiated HepaRG cells using
      nanoliquid chromatography-tandem mass spectrometry to identify the differences
      between the proteomes and the changes that lead to differentiation of these
      cells. We followed up on differentially-regulated proteins in hepatocytes- and
      biliary-like cells, focusing on Cathepsins D and K, Cyclophilin A, Annexin 1/A1,
      PDI and PDI A4/ERp72. Major differences between the two proteomes were found,
      including differentially regulated proteins, protein-protein interactions and
      intracellular localizations following differentiation. The results advance our
      current understanding of HepaRG differentiation and the unique properties of
      these cells. 

PMID- 23977167
TI  - HPat a decapping activator interacting with the miRNA effector complex.
AB  - Animal miRNAs commonly mediate mRNA degradation and/or translational repression
      by binding to their target mRNAs. Key factors for miRNA-mediated mRNA degradation
      are the components of the miRNA effector complex (AGO1 and GW182) and the general
      mRNA degradation machinery (deadenylation and decapping enzymes). The CCR4-NOT1
      complex required for the deadenylation of target mRNAs is directly recruited to
      the miRNA effector complex. However, it is unclear whether the following
      decapping step is only a consequence of deadenylation occurring independent of
      the miRNA effector complex or e.g. decapping activators can get recruited to the
      miRNA effector complex. In this study we performed split-affinity purifications
      in Drosophila cells and provide evidence for the interaction of the decapping
      activator HPat with the miRNA effector complex. Furthermore, in knockdown
      analysis of various mRNA degradation factors we demonstrate the importance of
      NOT1 for this interaction. This suggests that deadenylation and/or the
      recruitment of NOT1 protein precedes the association of HPat with the miRNA
      effector complex. Since HPat couples deadenylation and decapping, the recruitment
      of HPat to the miRNA effector complex provides a mechanism to commit the mRNA
      target for degradation. 

PMID- 23977168
TI  - Discontinuous patterns of brain activation in the psychotherapy process of
      obsessive-compulsive disorder: converging results from repeated FMRI and daily
      self-reports.
AB  - This study investigates neuronal activation patterns during the psychotherapeutic
      process, assuming that change dynamics undergo critical instabilities and
      discontinuous transitions. An internet-based system was used to collect daily
      self-assessments during inpatient therapies. A dynamic complexity measure was
      applied to the resulting time series. Critical phases of the change process were
      indicated by the maxima of the varying complexity. Repeated functional magnetic
      resonance imaging (fMRI) measurements were conducted over the course of the
      therapy. The study was realized with 9 patients suffering from obsessive
      compulsive disorder (subtype: washing/contamination fear) and 9 matched healthy
      controls. For symptom-provocative stimulation individualized pictures from
      patients' personal environments were used. The neuronal responses to these
      disease-specific pictures were compared to the responses during standardized
      disgust-provoking and neutral pictures. Considerably larger neuronal changes in
      therapy-relevant brain areas (cingulate cortex/supplementary motor cortex,
      bilateral dorsolateral prefrontal cortex, bilateral insula, bilateral parietal
      cortex, cuneus) were observed during critical phases (order transitions), as
      compared to non-critical phases, and also compared to healthy controls. The data
      indicate that non-stationary changes play a crucial role in the psychotherapeutic
      process supporting self-organization and complexity models of therapeutic change.

PMID- 23977169
TI  - The function and significance of SELENBP1 downregulation in human bronchial
      epithelial carcinogenic process.
AB  - BACKGROUND: Our quantitative proteomic study showed that selenium-binding protein
      1 (SELENBP1) was progressively decreased in human bronchial epithelial
      carcinogenic process. However, there is little information on expression and
      function of SELENBP1 during human lung squamous cell cancer (LSCC)
      carcinogenesis. METHODS: iTRAQ-tagging combined with 2D LC-MS/MS analysis was
      used to identify differentially expressed proteins in the human bronchial
      epithelial carcinogenic process. SELENBP1, member of selenoproteins family and
      progressively downregulated in this process, was selected to further study. Both
      Western blotting and immunohistochemistry were performed to detect SELENBP1
      expression in independent sets of tissues of bronchial epithelial carcinogenesis,
      and ability of SELENBP1 for discriminating NBE (normal bronchial epithelium) from
      preneoplastic lesions from invasive LSCC was evaluated. The effects of SELENBP1
      downregulation on the susceptibility of benzo(a)pyrene (B[a]P)-induced human
      bronchial epithelial cell transformation were determined. RESULTS: 102
      differentially expressed proteins were identified by quantitative proteomics, and
      SELENBP1 was found and confirmed being progressively decreased in the human
      bronchial epithelial carcinogenic process. The sensitivity and specificity of
      SELENBP1 were 80% and 79% in discriminating NBE from preneoplastic lesions, 79%
      and 82% in discriminating NBE from invasive LSCC, and 77% and 71% in
      discriminating preneoplastic lesions from invasive LSCC, respectively.
      Furthermore, knockdown of SELENBP1 in immortalized human bronchial epithelial
      cell line 16HBE cells significantly increased the efficiency of B[a]P-induced
      cell transformation. CONCLUSIONS: The present data shows for the first time that
      decreased SELENBP1 is an early event in LSCC, increases B[a]P-induced human
      bronchial epithelial cell transformation, and might serve as a novel potential
      biomarker for early detection of LSCC.

PMID- 23977170
TI  - Contribution of dopamine d1/5 receptor modulation of post-spike/burst
      afterhyperpolarization to enhance neuronal excitability of layer v pyramidal
      neurons in prepubertal rat prefrontal cortex.
AB  - Dopamine (DA) receptors in the prefrontal cortex (PFC) modulate both synaptic and
      intrinsic plasticity that may contribute to cognitive processing. However, the
      ionic basis underlying DA actions to enhance neuronal plasticity in PFC remains
      ill-defined. Using whole-cell patch-clamp recordings in layer V-VI pyramidal
      cells in prepubertal rat PFC, we showed that DA, via activation of D1/5, but not
      D2/3/4, receptors suppress a Ca(2+)-dependent, apamin-sensitive K(+) channel that
      mediates post-spike/burst afterhyperpolarization (AHP) to enhance neuronal
      excitability of PFC neurons. This inhibition is not dependent on HCN channels.
      The D1/5 receptor activation also enhanced an afterdepolarizing potential (ADP)
      that follows the AHP. Additional single-spike analyses revealed that DA or D1/5
      receptor activation suppressed the apamin-sensitive post-spike mAHP, further
      contributing to the increase in evoked spike firing to enhance the neuronal
      excitability. Taken together, the D1/5 receptor modulates intrinsic mechanisms
      that amplify a long depolarizing input to sustain spike firing outputs in
      pyramidal PFC neurons. 

PMID- 23977171
TI  - A role for NF-kappaB activity in skin hyperplasia and the development of
      keratoacanthomata in mice.
AB  - BACKGROUND: Previous studies have implicated NF-kappaB signaling in both
      cutaneous development and oncogenesis. However, these studies have been limited
      in part by the lethality that results from extreme over- or under-expression of
      NF-kappaB in available mouse models. Even cre-driven tissue specific expression
      of transgenes, or targeted deletion of NF-kappaB can cause cell death. Therefore,
      the present study was undertaken to evaluate a novel mouse model of enhanced NF
      kappaB activity in the skin. METHODS: A knock-in homologous recombination
      technique was utilized to develop a mouse model (referred to as PD mice) with
      increased NF-kappaB activity. RESULTS: The data show that increased NF-kappaB
      activity leads to hyperproliferation and dysplasia of the mouse epidermis.
      Chemical carcinogenesis in the context of enhanced NF-kappaB activity promotes
      the development of keratoacanthomata. CONCLUSION: Our findings support an
      important role for NF-kappaB in keratinocyte dysplasia. We have found that
      enhanced NF-kappaB activity renders keratinocytes susceptible to
      hyperproliferation and keratoacanthoma (KA) development but is not sufficient for
      transformation and SCC development. We therefore propose that NF-kappaB
      activation in the absence of additional oncogenic events can promote TNF
      dependent, actinic keratosis-like dysplasia and TNF-independent, KAs upon
      chemical carcinogensis. These studies suggest that resolution of KA cannot occur
      when NF-kappaB activation is constitutively enforced.

PMID- 23977172
TI  - Relationships of disability with age among adults aged 50 to 85: evidence from
      the United States, England and continental europe.
AB  - OBJECTIVES: To extend existing research on the US health disadvantage relative to
      Europe by studying the relationships of disability with age from midlife to old
      age in the US and four European regions (England/Northern and Western
      Europe/Southern Europe/Eastern Europe) including their wealth-related
      differences, using a flexible statistical approach to model the age-functions.
      METHODS: We used data from three studies on aging, with nationally representative
      samples of adults aged 50 to 85 from 15 countries (N = 48225): the US-American
      Health and Retirement Study (HRS), the English Longitudinal Study of Ageing
      (ELSA) and the Survey of Health, Ageing and Retirement in Europe (SHARE).
      Outcomes were mobility limitations and limitations in instrumental activities of
      daily living. We applied fractional polynomials of age to determine best fitting
      functional forms for age on disability in each region, while controlling for
      socio-demographic characteristics and important risk factors (hypertension,
      diabetes, obesity, smoking, physical inactivity). RESULTS: Findings showed high
      levels of disability in the US with small age-related changes between 50 and 85.
      Levels of disability were generally lower in Eastern Europe, followed by England
      and Southern Europe and lowest in Northern and Western Europe. In these latter
      countries age-related increases of disability, though, were steeper than in the
      US, especially in Eastern and Southern Europe. For all countries and at all ages,
      disability levels were higher among adults with low wealth compared to those with
      high wealth, with largest wealth-related differences among those in early old age
      in the USA. CONCLUSIONS: This paper illustrates considerable variations of
      disability and its relationship with age. It supports the hypothesis that less
      developed social policies and more pronounced socioeconomic inequalities are
      related to higher levels of disability and an earlier onset of disability.

PMID- 23977173
TI  - The FTO gene rs9939609 polymorphism predicts risk of cardiovascular disease: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: Genome-wide association studies have shown that variance in the fat
      mass- and obesity- associated gene (FTO) is associated with risk of obesity in
      Europeans and Asians. Since obesity is associated with an increased risk of
      cardiovascular disease (CVD), several studies have investigated the association
      between variant in the FTO gene and CVD risk, with inconsistent results. In this
      study, we performed a meta-analysis to clarify the association of rs9939609
      variant (or its proxies [r (2)>0.90]) in the FTO gene with CVD risk. METHODS:
      Published literature from PubMed and Embase was retrieved. Pooled odds ratios
      with 95% confidence intervals were calculated using the fixed- or random- effects
      model. RESULTS: A total of 10 studies (comprising 19,153 CVD cases and 103,720
      controls) were included in the meta-analysis. The results indicated that the
      rs9939609 variant was significantly associated with CVD risk (odds ratio = 1.18,
      95% confidence interval = 1.07-1.30, p = 0.001 [Z test], I (2) = 80.6%, p<0.001
      [heterogeneity]), and there was an insignificant change after adjustment for body
      mass index (BMI) and other conventional CVD risk factors (odds ratio = 1.16, 95%
      confidence interval = 1.05-1.27, p = 0.003 [Z test], I (2) = 75.4%, p<0.001
      [heterogeneity]). CONCLUSIONS: The present meta-analysis confirmed the
      significant association of the rs9939609 variant in the FTO gene with CVD risk,
      which was independent of BMI and other conventional CVD risk factors.

PMID- 23977174
TI  - FOXP3 subcellular localization predicts recurrence in oral squamous cell
      carcinoma.
AB  - Forkhead box protein P3 (FOXP3) expression in tumor infiltrating CD4(+)T cells is
      generally associated with an intrinsic capacity to suppress tumor immunity. Based
      on this notion, different studies have evaluated the prognostic value of this
      maker in cancer but contradictory results have been found. Indeed, even within
      the same cancer population, the presence of CD4(+)FOXP3(+)T cells has been
      associated,with either a poor or a good prognosis, or no correlation has
      beenfound. Here, we demonstrate,in patients with oral squamous cell carcinoma
      (OSCC), that what really represents a prognostic parameter is not the overall
      expression of FOXP3 but its intracellular localization.While overallFOXP3
      expression in tumor infiltrating CD4(+)T cells does not correlate with tumor
      recurrence, its intracellular localization within the CD4 cells does: nuclear
      FOXP3 (nFOXP3) is associated with tumor recurrence within 3 years, while
      cytoplasmicFOXP3 (cFOXP3) is associated with a lower likelihood of recurrence.
      Thus, we propose elevated levels of the cFOXP3/nFOXP3 ratio within tumor
      infiltrating CD4(+) T cells as a predictor of OSCC recurrence. 

PMID- 23977175
TI  - Towards a solution to the goose-agriculture conflict in North Norway, 1988-2012:
      the interplay between policy, stakeholder influence and goose population
      dynamics.
AB  - This paper presents results from a multidisciplinary study of a negotiation
      process between farmers and wildlife authorities which led to an agricultural
      subsidy scheme to alleviate conflicts between agriculture and geese in Norway.
      The Svalbard-breeding population of pink-footed geese Anser brachyrhynchus has
      increased considerably over the last decades and conflicts with farmers have
      escalated, especially at stopover sites in spring when geese feed on newly
      sprouted pasture grass. In Vesteralen, an important stopover site for geese in
      North Norway, farmers deployed scaring of geese at varying intensity dependent on
      the level of conflict during 1988-2012. We assessed the efficiency of a subsidy
      scheme established in 2006, in terms of its conflict mitigation, reflected in a
      near discontinuation of scaring activities. The presence of pink-footed geese was
      analysed in relation to scaring intensity, the total goose population size and
      the increasing occurrence of another goose species, the barnacle goose Branta
      leucopsis. Scaring significantly affected the number of geese staging in
      Vesteralen, both in absolute and relative terms (controlling for total population
      size). The geese responded immediately to an increased, and reduced, level of
      scaring. Despite the establishment of the subsidy scheme, the number of pink
      footed geese has recently declined which is probably caused by the increasing
      number of barnacle geese. For the farmers, the subsidy scheme provides funding
      that reduces the economic costs caused by the geese. Sustaining a low level of
      conflict will require close monitoring, dialogue and adaptation of the subsidy
      scheme to cater for changes in goose population dynamics. 

PMID- 23977176
TI  - Octyl gallate markedly promotes anti-amyloidogenic processing of APP through
      estrogen receptor-mediated ADAM10 activation.
AB  - Our previous studies showed that the green tea-derived polyphenolic compound (-)
      epigallocatechin-3 gallate (EGCG) reduces amyloid-beta (Abeta) production in both
      neuronal and mouse Alzheimer's disease (AD) models in concert with activation of
      estrogen receptor-alpha/phosphatidylinositide 3-kinase/protein kinase B
      (ERalpha/PI3K/Akt) signaling and anti-amyloidogenic amyloid precursor protein
      (APP) alpha-secretase (a disintegrin and metallopeptidase domain-10, ADAM10)
      processing. Since the gallate moiety in EGCG may correspond to the 7alpha
      position of estrogen, thereby facilitating ER binding, we extensively screened
      the effect of other gallate containing phenolic compounds on APP anti
      amyloidogenic processing. Octyl gallate (OG; 10 uM), drastically decreased Abeta
      generation, in concert with increased APP alpha-proteolysis, in murine neuron
      like cells transfected with human wild-type APP or "Swedish" mutant APP. OG
      markedly increased production of the neuroprotective amino-terminal APP cleavage
      product, soluble APP-alpha (sAPPalpha). In accord with our previous study, these
      cleavage events were associated with increased ADAM10 maturation and reduced by
      blockade of ERalpha/PI3k/Akt signaling. To validate these findings in vivo, we
      treated Abeta-overproducing Tg2576 mice with OG daily for one week by
      intracerebroventricular injection and found decreased Abeta levels associated
      with increased sAPPalpha. These data indicate that OG increases anti
      amyloidogenic APP alpha-secretase processing by activation of ERalpha/PI3k/Akt
      signaling and ADAM10, suggesting that this compound may be an effective treatment
      for AD. 

PMID- 23977177
TI  - Connected text reading and differences in text reading fluency in adult readers.
AB  - The process of connected text reading has received very little attention in
      contemporary cognitive psychology. This lack of attention is in parts due to a
      research tradition that emphasizes the role of basic lexical constituents, which
      can be studied in isolated words or sentences. However, this lack of attention is
      in parts also due to the lack of statistical analysis techniques, which
      accommodate interdependent time series. In this study, we investigate text
      reading performance with traditional and nonlinear analysis techniques and show
      how outcomes from multiple analyses can used to create a more detailed picture of
      the process of text reading. Specifically, we investigate reading performance of
      groups of literate adult readers that differ in reading fluency during a self
      paced text reading task. Our results indicate that classical metrics of reading
      (such as word frequency) do not capture text reading very well, and that
      classical measures of reading fluency (such as average reading time) distinguish
      relatively poorly between participant groups. Nonlinear analyses of distribution
      tails and reading time fluctuations provide more fine-grained information about
      the reading process and reading fluency. 

PMID- 23977178
TI  - Translating evidence for low back pain management into a consumer-focussed
      resource for use in community pharmacies: a cluster-randomised controlled trial.
AB  - BACKGROUND: This cluster-randomised controlled trial determined the effectiveness
      of an evidence-based, pamphlet intervention in improving low back pain (LBP)
      related beliefs among pharmacy consumers. METHODS: THIRTY FIVE COMMUNITY
      PHARMACIES WERE RANDOMISED TO THREE GROUPS: pamphlet+education intervention [n =
      11]; pamphlet only intervention [n = 11]; control: usual care [n = 13].
      Eligibility requirements for clusters included: community-based pharmacies and
      proprietor participation consent. Pharmacy consumers (N = 317) aged 18-65 years
      currently experiencing LBP participated. Intervention group allocation depended
      on the pharmacy attended. Individual-level outcomes were measured at pre
      intervention (T0), at two (T1) and eight (T2) weeks post-intervention and
      included beliefs about LBP [Back Pain Beliefs Questionnaire (BBQ); Fear Avoidance
      Beliefs Questionnaire (FABQ)]. Secondary outcomes included pain severity,
      activity impairment and pamphlet perceived usefulness. Blinding to group
      allocation included primary investigators, outcome assessors and the
      statistician. Pharmacy staff and consumers were un-blinded. RESULTS: Of 35
      pharmacies recruited (317 consumers), no clusters were lost to follow-up. Follow
      up was available for n = 24 at 2 weeks only; n = 38 at 8 weeks only; n = 148 at
      both time points, with n = 148+24+38 = 210 analysed (107 excluded: no follow up).
      Adjusting for baseline scores demonstrated no significant differences in beliefs
      (2 or at 8 weeks) between pamphlet (with or without education) versus control, or
      between 'pamphlet with' versus 'without' education. Work-related fear (FABQ) was
      significantly lower in consumers receiving pamphlet (with or without education)
      versus control (difference -2.3, 95%CI: -4.4 to -0.2). There was no significant
      difference between "pamphlet with" versus "pamphlet without" groups. Consumers
      receiving the "pamphlet with" reported greater perceived usefulness than
      consumers receiving the "pamphlet without" (difference 0.9 (95%CI: 0.0 to 1.8)).
      CONCLUSION: Community pharmacies provided a feasible primary care portal for
      implementing evidence-based information. The associated improvement in work
      related LBP-beliefs for consumers receiving the pamphlet suggests this simple
      intervention may be a useful component of care. TRIAL REGISTRATION: ACTR.org.au
      ACTRN12611000053921.

PMID- 23977179
TI  - Can hydrographic data provide evidence that the rate of oceanic uptake of
      anthropogenic CO2 is increasing?
AB  - Predictions of the rate of accumulation of anthropogenic carbon dioxide in the
      Pacific Ocean near 32 degrees S and 150 degrees W based on the P16 surveys of
      1991 and 2005 and on the P06 surveys of 1992 and 2003 underestimate the amount
      found in the P06 survey of 2009-2010, suggesting an increasing uptake rate.
      Assuming the accumulation rate to be constant over the two decades, analyses
      using all five surveys lead to upward revision of the rates based only on the
      first four. On the other hand, accumulation rates estimated for 2003-2010 are
      significantly greater than those for 1991-2003, again suggesting an increasing
      uptake rate. In addressing this question it is important to acknowledge the
      limitations of the repeat hydrography and consequent uncertainties of estimated
      accumulation rates. 

PMID- 23977180
TI  - Warming reduces carbon losses from grassland exposed to elevated atmospheric
      carbon dioxide.
AB  - The flux of carbon dioxide (CO2) between terrestrial ecosystems and the
      atmosphere may ameliorate or exacerbate climate change, depending on the relative
      responses of ecosystem photosynthesis and respiration to warming temperatures,
      rising atmospheric CO2, and altered precipitation. The combined effect of these
      global change factors is especially uncertain because of their potential for
      interactions and indirectly mediated conditions such as soil moisture. Here, we
      present observations of CO2 fluxes from a multi-factor experiment in semi-arid
      grassland that suggests a potentially strong climate - carbon cycle feedback
      under combined elevated [CO2] and warming. Elevated [CO2] alone, and in
      combination with warming, enhanced ecosystem respiration to a greater extent than
      photosynthesis, resulting in net C loss over four years. The effect of warming
      was to reduce respiration especially during years of below-average precipitation,
      by partially offsetting the effect of elevated [CO2] on soil moisture and C
      cycling. Carbon losses were explained partly by stimulated decomposition of soil
      organic matter with elevated [CO2]. The climate - carbon cycle feedback observed
      in this semiarid grassland was mediated by soil water content, which was reduced
      by warming and increased by elevated [CO2]. Ecosystem models should incorporate
      direct and indirect effects of climate change on soil water content in order to
      accurately predict terrestrial feedbacks and long-term storage of C in soil. 

PMID- 23977181
TI  - Impact of Hfq on global gene expression and intracellular survival in Brucella
      melitensis.
AB  - Brucella melitensis is a facultative intracellular bacterium that replicates
      within macrophages. The ability of brucellae to survive and multiply in the
      hostile environment of host macrophages is essential to its virulence. The RNA
      binding protein Hfq is a global regulator that is involved in stress resistance
      and pathogenicity. Here we demonstrate that Hfq is essential for stress
      adaptation and intracellular survival in B. melitensis. A B. melitensis hfq
      deletion mutant exhibits reduced survival under environmental stresses and is
      attenuated in cultured macrophages and mice. Microarray-based transcriptome
      analyses revealed that 359 genes involved in numerous cellular processes were
      dysregulated in the hfq mutant. From these same samples the proteins were also
      prepared for proteomic analysis to directly identify Hfq-regulated proteins.
      Fifty-five proteins with significantly affected expression were identified in the
      hfq mutant. Our results demonstrate that Hfq regulates many genes and/or proteins
      involved in metabolism, virulence, and stress responses, including those
      potentially involved in the adaptation of Brucella to the oxidative, acid, heat
      stress, and antibacterial peptides encountered within the host. The dysregulation
      of such genes and/or proteins could contribute to the attenuated hfq mutant
      phenotype. These findings highlight the involvement of Hfq as a key regulator of
      Brucella gene expression and facilitate our understanding of the role of Hfq in
      environmental stress adaptation and intracellular survival of B. melitensis. 

PMID- 23977183
TI  - The use of bayesian latent class cluster models to classify patterns of cognitive
      performance in healthy ageing.
AB  - The main focus of this study is to illustrate the applicability of latent class
      analysis in the assessment of cognitive performance profiles during ageing.
      Principal component analysis (PCA) was used to detect main cognitive dimensions
      (based on the neurocognitive test variables) and Bayesian latent class analysis
      (LCA) models (without constraints) were used to explore patterns of cognitive
      performance among community-dwelling older individuals. Gender, age and number of
      school years were explored as variables. Three cognitive dimensions were
      identified: general cognition (MMSE), memory (MEM) and executive (EXEC) function.
      Based on these, three latent classes of cognitive performance profiles (LC1 to
      LC3) were identified among the older adults. These classes corresponded to
      stronger to weaker performance patterns (LC1>LC2>LC3) across all dimensions; each
      latent class denoted the same hierarchy in the proportion of males, age and
      number of school years. Bayesian LCA provided a powerful tool to explore
      cognitive typologies among healthy cognitive agers. 

PMID- 23977182
TI  - Differential modulation of functional dynamics and allosteric interactions in the
      Hsp90-cochaperone complexes with p23 and Aha1: a computational study.
AB  - Allosteric interactions of the molecular chaperone Hsp90 with a large cohort of
      cochaperones and client proteins allow for molecular communication and event
      coupling in signal transduction networks. The integration of cochaperones into
      the Hsp90 system is driven by the regulatory mechanisms that modulate the
      progression of the ATPase cycle and control the recruitment of the Hsp90
      clientele. In this work, we report the results of computational modeling of
      allosteric regulation in the Hsp90 complexes with the cochaperones p23 and Aha1.
      By integrating protein docking, biophysical simulations, modeling of allosteric
      communications, protein structure network analysis and the energy landscape
      theory we have investigated dynamics and stability of the Hsp90-p23 and Hsp90
      Aha1 interactions in direct comparison with the extensive body of structural and
      functional experiments. The results have revealed that functional dynamics and
      allosteric interactions of Hsp90 can be selectively modulated by these
      cochaperones via specific targeting of the regulatory hinge regions that could
      restrict collective motions and stabilize specific chaperone conformations. The
      protein structure network parameters have quantified the effects of cochaperones
      on conformational stability of the Hsp90 complexes and identified dynamically
      stable communities of residues that can contribute to the strengthening of
      allosteric interactions. According to our results, p23-mediated changes in the
      Hsp90 interactions may provide "molecular brakes" that could slow down an
      efficient transmission of the inter-domain allosteric signals, consistent with
      the functional role of p23 in partially inhibiting the ATPase cycle. Unlike p23,
      Aha1-mediated acceleration of the Hsp90-ATPase cycle may be achieved via
      modulation of the equilibrium motions that facilitate allosteric changes favoring
      a closed dimerized form of Hsp90. The results of our study have shown that Aha1
      and p23 can modulate the Hsp90-ATPase activity and direct the chaperone cycle by
      exerting the precise control over structural stability, global movements and
      allosteric communications in Hsp90. 

PMID- 23977184
TI  - A decade of invasive meningococcal disease surveillance in Poland.
AB  - BACKGROUND: Neisseria meningitidis is a leading etiologic agent of severe
      invasive disease. The objective of the study was to characterise invasive
      meningococcal disease (IMD) epidemiology in Poland during the last decade, based
      on laboratory confirmed cases. METHODS: The study encompassed all invasive
      meningococci collected between 2002 and 2011 in the National Reference Centre for
      Bacterial Meningitis. The isolates were re-identified and characterised by
      susceptibility testing, MLST analysis, porA and fetA sequencing. A PCR technique
      was used for meningococcal identification directly from clinical materials.
      RESULTS: In the period studied, 1936 cases of IMD were confirmed, including 75.6%
      identified by culture. Seven IMD outbreaks, affecting mostly adolescents, were
      reported; all were caused by serogroup C meningococci of ST-11. The highest
      incidence was observed among children under one year of age (15.71/100,000 in
      2011). The general case fatality rate in the years 2010-2011 was 10.0%.
      Meningococci of serogroup B, C, Y and W-135 were responsible for 48.8%, 36.6%,
      1.2% and 1.2% of cases, respectively. All isolates were susceptible to third
      generation cephalosporins, chloramphenicol, ciprofloxacin, and 84.2% were
      susceptible to penicillin. MLST analysis (2009-2011) revealed that among
      serogroup B isolates the most represented were clonal complexes (CC) ST-32CC, ST
      18CC, ST-41/44CC, ST-213CC and ST-269CC, and among serogroup C: ST-103CC, ST
      41/44CC and ST-11CC. CONCLUSIONS: The detection of IMD in Poland has changed over
      time, but observed increase in the incidence of the disease was mostly attributed
      to changes in the surveillance system including an expanded case definition and
      inclusion of data from non-culture diagnostics.

PMID- 23977185
TI  - Contributions of ocular surface components to matrix-metalloproteinases (MMP)-2
      and MMP-9 in feline tears following corneal epithelial wounding.
AB  - PURPOSE: This study investigated ocular surface components that contribute to
      matrix-metalloproteinase (MMP)-2 and MMP-9 found in tears following corneal
      epithelial wounding. METHODS: Laboratory short-haired cats underwent corneal
      epithelial debridement in one randomly chosen eye (n = 18). Eye-flush tears were
      collected at baseline and during various healing stages. Procedural control eyes
      (identical experimental protocol as wounded eyes except for wounding, n = 5)
      served as controls for tear analysis. MMP activity was analyzed in tears using
      gelatin zymography. MMP staining patterns were evaluated in ocular tissues using
      immunohistochemistry and used to determine MMP expression sites responsible for
      tear-derived MMPs. RESULTS: The proMMP-2 and proMMP-9 activity in tears was
      highest in wounded and procedural control eyes during epithelial migration (8 to
      36 hours post-wounding). Wounded eyes showed significantly higher proMMP-9 in
      tears only during and after epithelial restratification (day 3 to 4 and day 7 to
      28 post-wounding, respectively) as compared to procedural controls (p<0.05).
      Tears from wounded and procedural control eyes showed no statistical differences
      for pro-MMP-2 and MMP-9 (p>0.05). Immunohistochemistry showed increased MMP-2 and
      MMP-9 expression in the cornea during epithelial migration and wound closure. The
      conjunctival epithelium exhibited highest levels of both MMPs during wound
      closure, while MMP-9 expression was reduced in conjunctival goblet cells during
      corneal epithelial migration followed by complete absence of the cells during
      wound closure. The immunostaining for both MMPs was elevated in the lacrimal
      gland during corneal healing, with little/no change in the meibomian glands.
      Conjunctival-associated lymphoid tissue (CALT) showed weak MMP-2 and intense MMP
      9 staining. CONCLUSIONS: Following wounding, migrating corneal epithelium
      contributed little to the observed MMP levels in tears. The major sources
      assessed in the present study for tear-derived MMP-2 and MMP-9 following corneal
      wounding are the lacrimal gland and CALT. Other sources included stromal
      keratocytes and conjunctiva with goblet cells.

PMID- 23977186
TI  - Enhanced nasal mucosal delivery and immunogenicity of anti-caries DNA vaccine
      through incorporation of anionic liposomes in chitosan/DNA complexes.
AB  - The design of optimized nanoparticles offers a promising strategy to enable DNA
      vaccines to cross various physiological barriers for eliciting a specific and
      protective mucosal immunity via intranasal administration. Here, we reported a
      new designed nanoparticle system through incorporating anionic liposomes (AL)
      into chitosan/DNA (CS/DNA) complexes. With enhanced cellular uptake, the
      constructed AL/CS/DNA nanoparticles can deliver the anti-caries DNA vaccine pGJA
      P/VAX into nasal mucosa. TEM results showed the AL/CS/DNA had a spherical
      structure. High DNA loading ability and effective DNA protection against nuclease
      were proved by gel electrophoresis. The surface charge of the AL/CS/DNA depended
      strongly on pH environment, enabling the intracellular release of loaded DNA via
      a pH-mediated manner. In comparison to the traditional CS/DNA system, our new
      design rendered a higher transfection efficiency and longer residence time of the
      AL/CS/DNA at nasal mucosal surface. These outstanding features enable the
      AL/CS/DNA to induce a significantly (p<0.01) higher level of secretory IgA (SIgA)
      than the CS/DNA in animal study, and a longer-term mucosal immunity. On the other
      hand, the AL/CS/DNA exhibited minimal cytotoxicity. These results suggest that
      the developed nanoparticles offer a potential platform for DNA vaccine packaging
      and delivery for more efficient elicitation of mucosal immunity. 

PMID- 23977187
TI  - The genetic diversity of the Nguni breed of African Cattle (Bos spp.): complete
      mitochondrial genomes of haplogroup T1.
AB  - Domesticated cattle were commonplace in northern Africa by about 7,000 years ago.
      Archaeological evidence, however, suggests they were not established in southern
      Africa until much later, no earlier than 2,000 years ago. Genetic reconstructions
      have started to shed light on the movement of African cattle, but efforts have
      been frustrated by a lack of data south of Ethiopia and the nature of the
      mitochondrial haplogroup T1 which is almost fixed across the continent. We
      sequenced 35 complete mitochondrial genomes from a South African herd of Nguni
      cattle, a breed historically associated with Bantu speaking farmers who were
      among the first to bring cattle to southern Africa. As expected, all individuals
      in the study were found to be members of haplogroup T1. Only half of the sub
      haplogroups of T1 (T1a-T1f) are represented in our sample and the overwhelming
      majority (94%) in this study belong to subhaplogroup T1b. A previous study of
      African cattle found frequencies of T1b of 27% in Egypt and 69% in Ethiopia.
      These results are consistent with serial multiple founder effects significantly
      shaping the gene pool as cattle were moved from north to south across the
      continent. Interestingly, these mitochondrial data give no indication that the
      impacts of the founder effects were ameliorated by gene flow from recently
      introduced Indian cattle breeds. 

PMID- 23977188
TI  - Molecular and functional analysis of UDP-N-acetylglucosamine Pyrophosphorylases
      from the Migratory Locust, Locusta migratoria.
AB  - UDP-N-acetylglucosamine pyrophosphorylases (UAP) function in the formation of
      extracellular matrix by producing N-acetylglucosamine (GlcNAc) residues needed
      for chitin biosynthesis and protein glycosylation. Herein, we report two UAP
      cDNA's derived from two different genes (LmUAP1 and LmUAP2) in the migratory
      locust Locusta migratoria. Both the cDNA and their deduced amino acid sequences
      showed about 70% identities between the two genes. Phylogenetic analysis suggests
      that LmUAP1 and LmUAP2 derive from a relatively recent gene duplication event.
      Both LmUAP1 and LmUAP2 were widely expressed in all the major tissues besides
      chitin-containing tissues. However, the two genes exhibited different
      developmental expression patterns. High expression of LmUAP1 was detected during
      early embryogenesis, then decreased greatly, and slowly increased before egg
      hatch. During nymphal development, the highest expression of LmUAP1 appeared just
      after molting but declined in each inter-molting period and then increased before
      molting to the next stage, whereas LmUAP2 was more consistently expressed
      throughout all these stages. When the early second- and fifth-instar nymphs (1
      day-old) were injected with LmUAP1 double-stranded RNA (dsRNA), 100% mortality
      was observed 2 days after the injection. When the middle second- and fifth-instar
      nymphs (3- to 4-day-old) were injected with LmUAP1 dsRNA, 100% mortality was
      observed during their next molting process. In contrast, when the insects at the
      same stages were injected with LmUAP2 dsRNA, these insects were able to develop
      normally and molt to the next stage successfully. It is presumed that the
      lethality caused by RNAi of LmUAP1 is due to reduced chitin biosynthesis of the
      integument and midgut, whereas LmUAP2 is not essential for locust development at
      least in nymph stage. This study is expected to help better understand different
      functions of UAP1 and UAP2 in the locust and other insect species. 

PMID- 23977189
TI  - HIV-1 drug-resistance surveillance among treatment-experienced and -naive
      patients after the implementation of antiretroviral therapy in Ghana.
AB  - BACKGROUND: Limited HIV-1 drug-resistance surveillance has been carried out in
      Ghana since the implementation of antiretroviral therapy (ART). This study sought
      to provide data on the profile of HIV-1 drug resistance in ART-experienced and
      newly diagnosed individuals in Ghana. METHODS: Samples were collected from 101
      HIV-1-infected patients (32 ART-experienced cases with virological failure and 69
      newly diagnosed ART-naive cases, including 11 children), in Koforidua, Eastern
      region of Ghana, from February 2009 to January 2010. The pol gene sequences were
      analyzed by in-house HIV-1 drug-resistance testing. RESULTS: The most prevalent
      HIV-1 subtype was CRF02_AG (66.3%, 67/101) followed by unique recombinant forms
      (25.7%, 26/101). Among 31 ART-experienced adults, 22 (71.0%) possessed at least
      one drug-resistance mutation, and 14 (45.2%) had two-class-resistance to
      nucleoside and non-nucleoside reverse-transcriptase inhibitors used in their
      first ART regimen. Importantly, the number of accumulated mutations clearly
      correlated with the duration of ART. The most prevalent mutation was lamivudine
      resistance M184V (n = 12, 38.7%) followed by efavirenz/nevirapine-resistance
      K103N (n = 9, 29.0%), and zidovudine/stavudine-resistance T215Y/F (n = 6, 19.4%).
      Within the viral protease, the major nelfinavir-resistance mutation L90M was
      found in one case. No transmitted HIV-1 drug-resistance mutation was found in 59
      ART-naive adults, but K103N and G190S mutations were observed in one ART-naive
      child. CONCLUSIONS: Despite expanding accessibility to ART in Eastern Ghana, the
      prevalence of transmitted HIV-1 drug resistance presently appears to be low. As
      ART provision with limited options is scaled up nationwide in Ghana, careful
      monitoring of transmitted HIV-1 drug resistance is necessary.

PMID- 23977190
TI  - Factors affecting domestic water consumption in rural households upon access to
      improved water supply: insights from the Wei River Basin, China.
AB  - Comprehensively understanding water consumption behavior is necessary to design
      efficient and effective water use strategies. Despite global efforts to identify
      the factors that affect domestic water consumption, those related to domestic
      water use in rural regions have not been sufficiently studied, particularly in
      villages that have gained access to improved water supply. To address this gap,
      we investigated 247 households in eight villages in the Wei River Basin where
      three types of improved water supply systems are implemented. Results show that
      domestic water consumption in liters per capita per day was significantly
      correlated with water supply pattern and vegetable garden area, and significantly
      negatively correlated with family size and age of household head. Traditional
      hygiene habits, use of water appliances, and preference for vegetable gardening
      remain dominant behaviors in the villages with access to improved water supply.
      Future studies on rural domestic water consumption should pay more attention to
      user lifestyles (water appliance usage habits, outdoor water use) and cultural
      backgrounds (age, education). 

PMID- 23977192
TI  - Recall and reconsolidation of contextual fear memory: differential control by ERK
      and Zif268 expression dosage.
AB  - Compelling evidence points to the existence of independent cellular processes
      involved in the consolidation and reconsolidation of memory. For instance, a
      double dissociation has been reported between hippocampal Extracellular-Regulated
      Kinase-1/2 (ERK1/2) activity being necessary for contextual fear conditioning
      (CFC) consolidation but not reconsolidation. Conversely, hippocampal expression
      of the immediate early gene Zif268 is necessary for CFC reconsolidation but not
      consolidation. Since we previously reported that ERK1/2 controls the
      transcription of Zif268 in the hippocampus, we examined the precise role of
      ERK1/2 activity and Zif268 gene expression dosage in CFC memory processing. For
      this, we first assessed performance of Zif268 homozygous and heterozygous mutant
      mice in a CFC paradigm. Whereas Zif268-/- mice displayed a deficit of both
      consolidation and reconsolidation, Zif268+/- mice displayed a selective deficit
      of reconsolidation only, therefore pointing to the relationship between Zif268
      gene expression dosage and CFC memory processing. Zif268 gene expression dosage
      interfered with the reconsolidation process if and only if CFC memory was
      relatively recently encoded and directly reactivated. Furthermore, CFC memory
      strengthening previously reported to involve Zif268 expression in the hippocampus
      was spared in Zif268+/- mice. Finally, blocking ERK1/2 activity prior to CFC
      retrieval prevented the deficit of reconsolidation observed in Zif268+/- mice.
      Collectively, these results highlight a tight relationship between Zif268 gene
      expression dosage and CFC memory processing. They also suggest that ERK1/2
      activity upon CFC memory recall is necessary for its retrieval, a prerequisite
      for its reactivation and subsequent reconsolidation. 

PMID- 23977193
TI  - Availability of and ease of access to calorie information on restaurant websites.
AB  - OBJECTIVE: Offering calories on restaurant websites might be particularly
      important for consumer meal planning, but the availability of and ease of
      accessing this information are unknown. METHODS: We assessed websites for the top
      100 U.S. chain restaurants to determine the availability of and ease of access to
      calorie information as well as website design characteristics. We also examined
      potential predictors of calorie availability and ease of access. RESULTS: Eighty
      two percent of restaurants provided calorie information on their websites; 25%
      presented calories on a mobile-formatted website. On average, calories could be
      accessed in 2.35+/-0.99 clicks. About half of sites (51.2%) linked to calorie
      information via the homepage. Fewer than half had a separate section identifying
      healthful options (46.3%), or utilized interactive meal planning tools (35.4%).
      Quick service/fast casual, larger restaurants, and those with less expensive
      entrees and lower revenue were more likely to make calorie information available.
      There were no predictors of ease of access. CONCLUSION: Calorie information is
      both available and largely accessible on the websites of America's leading
      restaurants. It is unclear whether consumer behavior is affected by the
      variability in the presentation of calorie information.

PMID- 23977191
TI  - The beta-blocker Nebivolol Is a GRK/beta-arrestin biased agonist.
AB  - Nebivolol, a third generation beta-adrenoceptor (beta-AR) antagonist (beta
      blocker), causes vasodilation by inducing nitric oxide (NO) production. The
      mechanism via which nebivolol induces NO production remains unknown, resulting in
      the genesis of much of the controversy regarding the pharmacological action of
      nebivolol. Carvedilol is another beta-blocker that induces NO production. A
      prominent pharmacological mechanism of carvedilol is biased agonism that is
      independent of Galphas and involves G protein-coupled receptor kinase (GRK)/beta
      arrestin signaling with downstream activation of the epidermal growth factor
      receptor (EGFR) and extracellular signal-regulated kinase (ERK). Due to the
      pharmacological similarities between nebivolol and carvedilol, we hypothesized
      that nebivolol is also a GRK/beta-arrestin biased agonist. We tested this
      hypothesis utilizing mouse embryonic fibroblasts (MEFs) that solely express beta2
      ARs, and HL-1 cardiac myocytes that express beta1- and beta2-ARs and no
      detectable beta3-ARs. We confirmed previous reports that nebivolol does not
      significantly alter cAMP levels and thus is not a classical agonist. Moreover, in
      both cell types, nebivolol induced rapid internalization of beta-ARs indicating
      that nebivolol is also not a classical beta-blocker. Furthermore, nebivolol
      treatment resulted in a time-dependent phosphorylation of ERK that was
      indistinguishable from carvedilol and similar in duration, but not amplitude, to
      isoproterenol. Nebivolol-mediated phosphorylation of ERK was sensitive to
      propranolol (non-selective beta-AR-blocker), AG1478 (EGFR inhibitor), indicating
      that the signaling emanates from beta-ARs and involves the EGFR. Furthermore, in
      MEFs, nebivolol-mediated phosphorylation of ERK was sensitive to pharmacological
      inhibition of GRK2 as well as siRNA knockdown of beta-arrestin 1/2. Additionally,
      nebivolol induced redistribution of beta-arrestin 2 from a diffuse staining
      pattern into more intense punctate spots. We conclude that nebivolol is a beta2
      AR, and likely beta1-AR, GRK/beta-arrestin biased agonist, which suggests that
      some of the unique clinically beneficial effects of nebivolol may be due to
      biased agonism at beta1- and/or beta2-ARs. 

PMID- 23977194
TI  - Trends in the incidence of in situ and invasive cervical cancer by age group and
      histological type in Korea from 1993 to 2009.
AB  - OBJECTIVE: Our study aims to describe changes in carcinoma in situ (CIS) and
      invasive cervical carcinoma (ICC) in Korean women diagnosed between 1993 and
      2009. METHODS: All cases of CIS and invasive cervical carcinoma diagnosed from
      1993 to 2009 in the Korean National Cancer Incidence database were analyzed. Age
      standardized rates (ASRs) and annual percent changes (APCs) in incidence rates
      were compared according to age and histological type. Additionally, we used Korea
      National Health and Nutrition Examination Survey (KNHANES) to know the
      association between screening rate for cervical cancer and incidence rate of
      cervical cancer. RESULTS: Between 1993 and 2009, 72,240 cases of ICC were
      reported in Korea. Total incidence rate of ICC was 14.7 per 100,000 females. ASRs
      of ICC declined 3.8% per year, from 19.3 per 100,000 in 1993 to 10.5 per 100,000
      in 2009. Although the overall incidence rate of adenocarcinoma remained stable,
      invasive squamous cell carcinoma showed a decreasing trend (APC -4.2%). For women
      aged 60-79 years, ASRs for squamous cell carcinoma increased from 1993 to 2001,
      and decreased from 2001 to 2009 (APC: -4.6%). Total 62,300 cases of CIS were
      diagnosed from 1993 to 2009. Total incidence rate of CIS was 12.2 per 100,000
      females. ASRs of CIS increased 5.7% per year, from 7.5 per 100,000 in 1993 to
      19.0 per 100,000 in 2009. Adenocarcinoma in situ increased 13.2% per year. There
      was a strong positive correlation between screening rate for cervical cancer and
      incidence rate for CIS (p-value = 0.03) whereas screening rate showed a strong
      negative correlation with incidence rate for squamous ICC (p-value = 0.04).
      CONCLUSIONS: The increasing trend in CIS, coupled with a decreasing trend in ICC,
      suggests the important role of cervix cancer screening. The incidence of
      adenocarcinoma showed a plateau, but the incidence of adenocarcinoma in situ
      showed an increasing trend.

PMID- 23977195
TI  - A novel Golgi retention signal RPWS for tumor suppressor UBIAD1.
AB  - UBIAD1 plays critical roles in physiology including vitamin K and CoQ10
      biosynthesis as well as pathophysiology including dyslipimedia-induced SCD
      (Schnyder's corneal dystrophy), Parkinson's disease, cardiovascular disease and
      bladder carcinoma. Since the subcellular localization of UBIAD1 varies in
      different cell types, characterization of the exact subcellular localization of
      UBIAD1 in specific human disease is vital for understanding its molecular
      mechanism. As UBIAD1 suppresses bladder carcinoma, we studied its subcellular
      localization in human bladder carcinoma cell line T24. Since fluorescent images
      of UBIAD1-EGFP in T24, human prostate cancer cell line PC-3, human embryonic
      kidney cell line HEK293 and human hepatocyte cell line L02 are similar, these
      four cell lines were used for present study. Using a combination of fluorescent
      microscopy and immunohistochemistry, it was found that UBIAD1 localized on the
      Golgi and endoplasmic reticulum (ER), but not on the plasma membrane, of T24 and
      HEK293 cells. Using scanning electron microscopy and western blot analysis, we
      found that UBIAD1 is enriched in the Golgi fraction extracted from the L02 cells,
      verifying the Golgi localization of UBAID1. Site-directed mutagenesis showed that
      the RPWS motif, which forms an Arginine finger on the UBIAD1 N terminus, serves
      as the Golgi retention signal. With both cycloheximide and brefeldin A inhibition
      assays, it was shown that UBIAD1 may be transported from the endoplasmic
      reticulum (ER) to the Golgi by a COPII-mediated mechanism. Based upon flow
      cytometry analysis, it is shown that mutation of the RPWS motif reduced the
      UBIAD1-induced apoptosis of T24 cells, indicating that the proper Golgi
      localization of UBIAD1 influences its tumor suppressant activity. This study
      paves the way for further understanding the molecular mechanism of UBIAD1 in
      human diseases. 

PMID- 23977196
TI  - An iterative framework for EEG-based image search: robust retrieval with weak
      classifiers.
AB  - We revisit the framework for brain-coupled image search, where the
      Electroencephalography (EEG) channel under rapid serial visual presentation
      protocol is used to detect user preferences. Extending previous works on the
      synergy between content-based image labeling and EEG-based brain-computer
      interface (BCI), we propose a different perspective on iterative coupling.
      Previously, the iterations were used to improve the set of EEG-based image labels
      before propagating them to the unseen images for the final retrieval. In our
      approach we accumulate the evidence of the true labels for each image in the
      database through iterations. This is done by propagating the EEG-based labels of
      the presented images at each iteration to the rest of images in the database. Our
      results demonstrate a continuous improvement of the labeling performance across
      iterations despite the moderate EEG-based labeling (AUC <75%). The overall
      analysis is done in terms of the single-trial EEG decoding performance and the
      image database reorganization quality. Furthermore, we discuss the EEG-based
      labeling performance with respect to a search task given the same image database.

PMID- 23977197
TI  - Directed in vitro myogenesis of human embryonic stem cells and their in vivo
      engraftment.
AB  - Development of human embryonic stem cell (hESC)-based therapy requires derivation
      of in vitro expandable cell populations that can readily differentiate to
      specified cell types and engraft upon transplantation. Here, we report that hESCs
      can differentiate into skeletal muscle cells without genetic manipulation. This
      is achieved through the isolation of cells expressing a mesodermal marker,
      platelet-derived growth factor receptor-alpha (PDGFRA), following embryoid body
      (EB) formation. The ESC-derived cells differentiated into myoblasts in vitro as
      evident by upregulation of various myogenic genes, irrespective of the presence
      of serum in the medium. This result is further corroborated by the presence of
      sarcomeric myosin and desmin, markers for terminally differentiated cells. When
      transplanted in vivo, these pre-myogenically committed cells were viable in
      tibialis anterior muscles 14 days post-implantation. These hESC-derived cells,
      which readily undergo myogenic differentiation in culture medium containing
      serum, could be a viable cell source for skeletal muscle repair and tissue
      engineering to ameliorate various muscle wasting diseases. 

PMID- 23977198
TI  - Caffeine increases anaerobic work and restores cycling performance following a
      protocol designed to lower endogenous carbohydrate availability.
AB  - The purpose this study was to examine the effects of caffeine ingestion on
      performance and energy expenditure (anaerobic and aerobic contribution) during a
      4-km cycling time trial (TT) performed after a carbohydrate (CHO) availability
      lowering exercise protocol. After preliminary and familiarization trials, seven
      amateur cyclists performed three 4-km cycling TT in a double-blind, randomized
      and crossover design. The trials were performed either after no previous exercise
      (CON), or after a CHO availability-lowering exercise protocol (DEP) performed in
      the previous evening, followed by either placebo (DEP-PLA) or 5 mg.kg(-1) of
      caffeine intake (DEP-CAF) 1 hour before the trial. Performance was reduced (
      2.1%) in DEP-PLA vs CON (421.0+/-12.3 vs 412.4+/-9.7 s). However, performance was
      restored in DEP-CAF (404.6+/-17.1 s) compared with DEP-PLA, while no differences
      were found between DEP-CAF and CON. The anaerobic contribution was increased in
      DEP-CAF compared with both DEP-PLA and CON (67.4+/-14.91, 47. 3+/-14.6 and 55.3+/
      14.0 W, respectively), and this was more pronounced in the first 3 km of the
      trial. Similarly, total anaerobic work was higher in DEP-CAF than in the other
      conditions. The integrated electromyographic activity, plasma lactate
      concentration, oxygen uptake, aerobic contribution and total aerobic work were
      not different between the conditions. The reduction in performance associated
      with low CHO availability is reversed with caffeine ingestion due to a higher
      anaerobic contribution, suggesting that caffeine could access an anaerobic
      "reserve" that is not used under normal conditions. 

PMID- 23977199
TI  - Effects of androgen deprivation on cerebral morphometry in prostate cancer
      patients--an exploratory study.
AB  - BACKGROUND: Androgen deprivation therapy (ADT) is a common treatment for non
      metastatic, low-risk prostate cancer, but a potential side effect of ADT is
      impaired brain functioning. Previous work with functional magnetic resonance
      imaging (MRI) demonstrated altered prefrontal cortical activations in cognitive
      control, with undetectable changes in behavioral performance. Given the utility
      of brain imaging in identifying the potentially deleterious effects of ADT on
      brain functions, the current study examined the effects of ADT on cerebral
      structures using high resolution MRI and voxel-based morphometry (VBM). METHODS:
      High resolution T1 weighted image of the whole brain were acquired at baseline
      and six months after ADT for 12 prostate cancer patients and 12 demographically
      matched non-exposed control participants imaged at the same time points. Brain
      images were segmented into gray matter, white matter and cerebral ventricles
      using the VBM toolbox as implemented in Statistical Parametric Mapping 8.
      RESULTS: Compared to baseline scan, prostate cancer patients undergoing ADT
      showed decreased gray matter volume in frontopolar cortex, dorsolateral
      prefrontal cortex and primary motor cortex, whereas the non-exposed control
      participants did not show such changes. In addition, the decrease in gray matter
      volume of the primary motor cortex showed a significant correlation with longer
      reaction time to target detection in a working memory task. CONCLUSIONS: ADT can
      affect cerebral gray matter volumes in prostate cancer patients. If replicated,
      these results may facilitate future studies of cognitive function and quality of
      life in men receiving ADT, and can also help clinicians weigh the benefits and
      risks of hormonal therapy in the treatment of prostate cancer.

PMID- 23977200
TI  - Lats2 modulates adipocyte proliferation and differentiation via hippo signaling.
AB  - First identified in Drosophila and highly conserved in mammals, the Hippo pathway
      controls organ size. Lats2 is one of the core kinases of the Hippo pathway and
      plays major roles in cell proliferation by interacting with the downstream
      transcriptional cofactors YAP and TAZ. Although the function of the Hippo pathway
      and Lats2 is relatively well understood in several tissues and organs, less is
      known about the function of Lats2 and Hippo signaling in adipose development.
      Here, we show that Lats2 is an important modulator of adipocyte proliferation and
      differentiation via Hippo signaling. Upon activation, Lats2 phosphorylates YAP
      and TAZ, leading to their retention in the cytoplasm, preventing them from
      activating the transcription factor TEAD in the nucleus. Because TAZ remains in
      the cytoplasm, PPARgamma regains its transcriptional activity. Furthermore,
      cytoplasmic TAZ acts as an inhibitor of Wnt signaling by suppressing DVL2,
      thereby preventing beta-catenin from entering the nucleus to stimulate TCF/LEF
      transcriptional activity. The above effects contribute to the phenotype of
      repressed proliferation and accelerated differentiation in adipocytes. Thus,
      Lats2 regulates the balance between proliferation and differentiation during
      adipose development. Interestingly, our study provides evidence that Lats2 not
      only negatively modulates cell proliferation but also positively regulates cell
      differentiation. 

PMID- 23977201
TI  - Rotenone directly induces BV2 cell activation via the p38 MAPK pathway.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease.
      Although its pathogenesis is still unclear, increasing evidence suggests that
      mitochondrial dysfunction induced by environmental toxins, such as mitochondrial
      complex I inhibitors, plays a significant role in the disease process. The
      microglia in PD brains are highly activated, and inflammation is also an
      essential element in PD pathogenesis. However, the means by which these toxins
      activate microglia is still unclear. In the present study, we found that
      rotenone, a mitochondrial complex I inhibitor, could directly activate microglia
      via the nuclear factor kappa B (NF-kappaB) signaling pathway, thereby inducing
      significantly increased expression of inflammatory cytokines. We further observed
      that rotenone induced caspase-1 activation and mature IL-1beta release, both of
      which are strictly dependent on p38 mitogen-activated protein kinase (MAPK). The
      activation of p38 is associated with the presence of reactive oxygen species
      (ROS) produced by rotenone. Removal of these ROS abrogated the activation of the
      microglia. Therefore, our data suggest that the environmental toxin rotenone can
      directly activate microglia through the p38 MAPK pathway. 

PMID- 23977202
TI  - Innate immune detection of flagellin positively and negatively regulates
      salmonella infection.
AB  - Salmonella enterica serovar Typhimurium is a flagellated bacterium and one of the
      leading causes of gastroenteritis in humans. Bacterial flagellin is required for
      motility and also a prime target of the innate immune system. Innate immune
      recognition of flagellin is mediated by at least two independent pathways, TLR5
      and Naip5-Naip6/NlrC4/Caspase-1. The functional significance of each of the two
      independent flagellin recognition systems for host defense against wild type
      Salmonella infection is complex, and innate immune detection of flagellin
      contributes to both protection and susceptibility. We hypothesized that efficient
      modulation of flagellin expression in vivo permits Salmonella to evade innate
      immune detection and limit the functional role of flagellin-specific host innate
      defenses. To test this hypothesis, we used Salmonella deficient in the anti-sigma
      factor flgM, which overproduce flagella and are attenuated in vivo. In this study
      we demonstrate that flagellin recognition by the innate immune system is
      responsible for the attenuation of flgM(-) S. Typhimurium, and dissect the
      contribution of each flagellin recognition pathway to bacterial clearance and
      inflammation. We demonstrate that caspase-1 controls mucosal and systemic
      infection of flgM(-) S. Typhimurium, and also limits intestinal inflammation and
      injury. In contrast, TLR5 paradoxically promotes bacterial colonization in the
      cecum and systemic infection, but attenuates intestinal inflammation. Our results
      indicate that Salmonella evasion of caspase-1 dependent flagellin recognition is
      critical for establishing infection and that evasion of TLR5 and caspase-1
      dependent flagellin recognition helps Salmonella induce intestinal inflammation
      and establish a niche in the inflamed gut. 

PMID- 23977203
TI  - Unique kinase catalytic mechanism of AceK with a single magnesium ion.
AB  - Isocitrate dehydrogenase kinase/phosphatase (AceK) is the founding member of the
      protein phosphorylation system in prokaryotes. Based on the novel and unique
      structural characteristics of AceK recently uncovered, we sought to understand
      its kinase reaction mechanism, along with other features involved in the
      phosphotransfer process. Herein we report density functional theory QM
      calculations of the mechanism of the phosphotransfer reaction catalysed by AceK.
      The transition states located by the QM calculations indicate that the
      phosphorylation reaction, catalysed by AceK, follows a dissociative mechanism
      with Asp457 serving as the catalytic base to accept the proton delivered by the
      substrate. Our results also revealed that AceK prefers a single Mg(2+)-containing
      active site in the phosphotransfer reaction. The catalytic roles of conserved
      residues in the active site are discussed. 

PMID- 23977204
TI  - Monoubiquitination and activity of the paracaspase MALT1 requires glutamate 549
      in the dimerization interface.
AB  - The mucosa-associated lymphoid tissue protein-1 (MALT1, also known as
      paracaspase) is a protease whose activity is essential for the activation of
      lymphocytes and the growth of cells derived from human diffuse large B-cell
      lymphomas of the activated B-cell subtype (ABC DLBCL). Crystallographic
      approaches have shown that MALT1 can form dimers via its protease domain, but why
      dimerization is relevant for the biological activity of MALT1 remains largely
      unknown. Using a molecular modeling approach, we predicted Glu 549 (E549) to be
      localized within the MALT1 dimer interface and thus potentially relevant.
      Experimental mutation of this residue into alanine (E549A) led to a complete
      impairment of MALT1 proteolytic activity. This correlated with an impaired
      capacity of the mutant to form dimers of the protease domain in vitro, and a
      reduced capacity to promote NF-kappaB activation and transcription of the growth
      promoting cytokine interleukin-2 in antigen receptor-stimulated lymphocytes.
      Moreover, this mutant could not rescue the growth of ABC DLBCL cell lines upon
      MALT1 silencing. Interestingly, the MALT1 mutant E549A was unable to undergo
      monoubiquitination, which we identified previously as a critical step in MALT1
      activation. Collectively, these findings suggest a model in which E549 at the
      dimerization interface is required for the formation of the enzymatically active,
      monoubiquitinated form of MALT1. 

PMID- 23977205
TI  - Deletion of glutathione peroxidase-2 inhibits azoxymethane-induced colon cancer
      development.
AB  - The selenoprotein glutathione peroxidase-2 (GPx2) appears to have a dual role in
      carcinogenesis. While it protected mice from colon cancer in a model of
      inflammation-triggered carcinogenesis (azoxymethane and dextran sodium sulfate
      treatment), it promoted growth of xenografted tumor cells. Therefore, we analyzed
      the effect of GPx2 in a mouse model mimicking sporadic colorectal cancer
      (azoxymethane-treatment only). GPx2-knockout (KO) and wild-type (WT) mice were
      adjusted to an either marginally deficient (-Se), adequate (+Se), or
      supranutritional (++Se) selenium status and were treated six times with
      azoxymethane (AOM) to induce tumor development. In the -Se and ++Se groups, the
      number of tumors was significantly lower in GPx2-KO than in respective WT mice.
      On the +Se diet, the number of dysplastic crypts was reduced in GPx2-KO mice.
      This may be explained by more basal and AOM-induced apoptotic cell death in GPx2
      KO mice that eliminates damaged or pre-malignant epithelial cells. In WT
      dysplastic crypts GPx2 was up-regulated in comparison to normal crypts which
      might be an attempt to suppress apoptosis. In contrast, in the +Se groups tumor
      numbers were similar in both genotypes but tumor size was larger in GPx2-KO mice.
      The latter was associated with an inflammatory and tumor-promoting environment as
      obvious from infiltrated inflammatory cells in the intestinal mucosa of GPx2-KO
      mice even without any treatment and characterized as low-grade inflammation. In
      WT mice the number of tumors tended to be lowest in +Se compared to -Se and ++Se
      feeding indicating that selenium might delay tumorigenesis only in the adequate
      status. In conclusion, the role of GPx2 and presumably also of selenium depends
      on the cancer stage and obviously on the involvement of inflammation. 

PMID- 23977206
TI  - Runs of homozygosity associated with speech delay in autism in a taiwanese han
      population: evidence for the recessive model.
AB  - Runs of homozygosity (ROH) may play a role in complex diseases. In the current
      study, we aimed to test if ROHs are linked to the risk of autism and related
      language impairment. We analyzed 546,080 SNPs in 315 Han Chinese affected with
      autism and 1,115 controls. ROH was defined as an extended homozygous haplotype
      spanning at least 500 kb. Relative extended haplotype homozygosity (REHH) for the
      trait-associated ROH region was calculated to search for the signature of
      selection sweeps. Totally, we identified 676 ROH regions. An ROH region on
      11q22.3 was significantly associated with speech delay (corrected p = 1.73*10(
      8)). This region contains the NPAT and ATM genes associated with ataxia
      telangiectasia characterized by language impairment; the CUL5 (culin 5) gene in
      the same region may modulate the neuronal migration process related to language
      functions. These three genes are highly expressed in the cerebellum. No evidence
      for recent positive selection was detected on the core haplotypes in this region.
      The same ROH region was also nominally significantly associated with speech delay
      in another independent sample (p = 0.037; combinatorial analysis Stouffer's z
      trend = 0.0005). Taken together, our findings suggest that extended recessive
      loci on 11q22.3 may play a role in language impairment in autism. More research
      is warranted to investigate if these genes influence speech pathology by
      perturbing cerebellar functions. 

PMID- 23977207
TI  - Intravenous application of a primary sevoflurane metabolite improves outcome in
      murine septic peritonitis: first results.
AB  - Volatile anesthetics are known to have immunomodulatory effects in conditions of
      organ injury. A recent study in an experimental sepsis model has shown remarkably
      improved survival when mice were exposed to volatile anesthetics. In the present
      study, we show that hexafluoroisopropanol - a water-soluble primary sevoflurane
      metabolite - has beneficial effects on the overall survival in a murine model of
      cecal ligation and puncture. Seven-day survival as well as tissue damage markers
      including transaminases and high mobility group box protein-1 were assessed as
      measures of end organ damage. In animals undergoing cecal ligation and puncture
      procedure hexafluoroisopropanol conditioning - but not late postconditioning 24
      hours after sepsis induction - significantly increased survival rate (17% vs.
      77%, p = 0.037) and attenuated secretion of organ damage markers. This study
      shows survival benefits by administration of the metabolite of a volatile
      anesthetic. If successfully translated, hexafluoroisopropanol might offer
      interesting therapeutic opportunities in the future treatment of abdominal
      sepsis. 

PMID- 23977208
TI  - The views of healthcare professionals, drug developers and regulators on
      information about older people needed for rational drug prescription.
AB  - BACKGROUND: The ICH E7 guideline intends to improve the knowledge about medicines
      in geriatric patients. As a legislative document, it might not reflect the needs
      of healthcare professionals. This study investigated what information healthcare
      professionals, regulatory agencies and pharmaceutical industries consider
      necessary for rational drug prescribing to older individuals. METHODS AND
      FINDINGS: A 29-item-questionnaire was composed, considering the representation in
      trials, pharmacokinetics, efficacy, safety, and convenience of use in older
      individuals, with space for additions. Forty-three European professionals with an
      interest in medication for older individuals were included. In order to
      investigate their relevance, five items were included in a second questionnaire,
      with 11 control items. Median scores, differences between clinical and non
      clinical respondents and response consistency were analysed. Consistency was
      present in 10 control items. Therefore, all items of the first questionnaire and
      the five additional items were analysed. Thirty-seven (86%) respondents returned
      the first questionnaire; 31/37 (84%) the second. Information about age-related
      differences in adverse events, locomotor effects, drug-disease interactions,
      dosing instructions, and information about the proportion of included 65+
      patients was considered necessary by most respondents. Clinicians considered
      information significantly more important than the non-clinical respondents about
      the inclusion of 75+, time-until-benefit in older people, anticholinergic
      effects, drug-disease interactions, and convenience of use. Main study
      limitations are the focus on information for daily practice, while the ICH E7
      guideline is a legislative document focused on market approval of a new medicine.
      Also, a questionnaire with a Likert scale has its limitations; this was addressed
      by providing space for comments. CONCLUSIONS: This study reveals that items
      considered necessary are currently not included in the ICH E7 guideline. Also,
      clinicians' and non-clinicians' opinions differed significantly in 15% of the
      items. Therefore, all stakeholders should collaborate to improve the availability
      of information for the rational prescribing to older individuals.

PMID- 23977209
TI  - Feasibility of a novel functional sensibility test as an assisted examination for
      determining precision pinch performance in patients with carpal tunnel syndrome.
AB  - To understand the feasibility of a novel functional sensibility test for
      determining precision pinch performance in patients with carpal tunnel syndrome,
      this study investigates the validity, sensitivity and specificity of functional
      sensibility derived from a pinch-holding-up activity (PHUA) test. Participants
      include 70 clinically defined carpal tunnel syndrome (CTS) patients with 119
      involved hands and 70 age- and gender-matched controls. To examine the
      discriminating ability of the functional sensibility test, the differences in the
      ability of pinch force adjustments to the inertial load of handling object
      between CTS and control subjects are analyzed. The results of functional
      sensibility are correlated with the severity of CTS to establish concurrent
      validity. The receiver operating characteristic (ROC) curve is constructed to
      demonstrate the accuracy of the proposed test. The functional sensibility score
      significantly discriminates the patients and control groups (respectively,
      12.94+/-1.72 vs. 11.51+/-1.15N in peak pinch force (FPPeak), p<0.001; 2.92+/-0.41
      vs. 2.52+/-0.24 in force ratio, p<0.001) and is moderately correlated (r = 0.42
      0.54, p<0.001) with the results of traditional sensibility tests (touch-pressure
      threshold and two-point discrimination test). In addition, there is a statistical
      difference in the results of functional sensibility (p<0.001) among the subgroups
      of CTS severity based on electrophysiological study. The sensitivity and
      specificity are 0.79 and 0.76, respectively, for the functional sensibility test.
      The areas under the ROC curve are 0.85 and 0.80 for the force ratio and FPPeak,
      respectively. In conclusion, the functional sensibility test could be feasibly
      used as a clinical tool for determining both the sensibility and precision pinch
      performance of hands for the patients with CTS. 

PMID- 23977210
TI  - Uroplakin peptide-specific autoimmunity initiates interstitial cystitis/painful
      bladder syndrome in mice.
AB  - The pathophysiology of interstitial cystitis/painful bladder syndrome (IC/PBS) is
      enigmatic. Autoimmunity and impaired urothelium might lead the underlying
      pathology. A major shortcoming in IC/PBS research has been the lack of an
      appropriate animal model. In this study, we show that the bladder specific
      uroplakin 3A-derived immunogenic peptide UPK3A 65-84, which contains the binding
      motif for IA(d) MHC class II molecules expressed in BALB/c mice, is capable of
      inducing experimental autoimmune cystitis in female mice of that strain. A highly
      antigen-specific recall proliferative response of lymph node cells to UPK3A 65-84
      was observed, characterized by selectively activated CD4+ T cells with a
      proinflammatory Th1-like phenotype, including enhanced production of interferon
      gamma and interleukin-2. T cell infiltration of the bladder and bladder-specific
      increased gene expression of inflammatory cytokines were observed. Either active
      immunization with UPK3A 65-84 or adoptive transfer of peptide-activated CD4+ T
      cells induced all of the predominant IC/PBS phenotypic characteristics, including
      increased micturition frequency, decreased urine output per micturition, and
      increased pelvic pain responses to stimulation with von Frey filaments. Our study
      demonstrates the creation of a more specific experimental autoimmune cystitis
      model that is the first inducible model for IC/PBS that manifests all of the
      major symptoms of this debilitating condition. 

PMID- 23977211
TI  - I choose, therefore I like: preference for faces induced by arbitrary choice.
AB  - Behavioral choice alters one's preference rather than simply reflecting it. This
      effect to fit preferences with past choice, is known as "choice-induced
      preference change." After making a choice between two equally attractive options,
      one tends to rate the chosen option better than they initially did and/or the
      unchosen option worse. The present study examined how behavioral choice changes
      subsequent preference, using facial images for the choice options as well as
      blind choice techniques. Participants rated their facial preference for each
      face, and chose between two equally preferred faces and subsequently rated their
      facial preference. Results from four experiments demonstrated that randomly
      chosen faces were more preferred only after participants were required to choose
      "a preferred face," (in Experiment 1) but not "an unpreferred face," (in
      Experiment 2) or "a rounder face" (in Experiment 3). Further, preference change
      was still observed after participants were informed that choices were actually
      random (in Experiment 4). Our findings provide new and important implications
      characterizing the conditions under which random choice changes preference, and
      show that people are tempted to make a biased evaluation even after they know
      that they did not make the choice for themselves. 

PMID- 23977212
TI  - Decomposing effects of time on task reveals an anteroposterior gradient of
      perceptual decision regions.
AB  - In perceptual decision making, the selection of an appropriate action depends
      critically on an organism's ability to use sensory inputs to accumulate evidence
      for a decision. However, differentiating decision-related processes from effects
      of "time on task" can be difficult. Here we combine the response signal paradigm,
      in which the experimenter rather than the subject dictates the time of the
      response, and independent components analysis (ICA) to search for signatures
      consistent with time on task and decision making, respectively, throughout the
      brain. Using this novel approach, we identify two such independent components
      from BOLD activity related to a random dot motion task: one sensitive to the main
      effect of stimulus duration, and one to both the main effect of motion coherence
      and its interaction with duration. Furthermore, we demonstrate that these two
      components are expressed differently throughout the brain, with activity in
      occipital regions most reflective of the former, activity within intraparietal
      sulcus modulated by both factors, and more anterior regions including the
      anterior insula, pre-SMA, and inferior frontal sulcus driven almost exclusively
      by the latter. Consistent with these ICA findings, cluster analysis identifies a
      posterior-to-anterior gradient that differentiates regions sensitive to time on
      task from regions whose activity is strongly tied to motion coherence. Together,
      these findings demonstrate that progressively more anterior regions are likely to
      participate in progressively more proximate decision-related processes. 

PMID- 23977213
TI  - Differential modulation of TREM2 protein during postnatal brain development in
      mice.
AB  - During postnatal development, microglia, the resident innate immune cells of the
      central nervous system are constantly monitoring the brain parenchyma, cleaning
      the cell debris, the synaptic contacts overproduced and also maintaining the
      brain homeostasis. In this context, the postnatal microglia need some control
      over the innate immune response. One such molecule recently described to be
      involved in modulation of immune response is TREM2 (triggering receptor expressed
      on myeloid cells 2). Although some studies have observed TREM2 mRNA in postnatal
      brain, the regional pattern of the TREM2 protein has not been described. We
      therefore characterized the distribution of TREM2 protein in mice brain from
      Postnatal day (P) 1 to 14 by immunostaining. In our study, TREM2 protein was
      expressed only in microglia/macrophages and is developmentally downregulated in a
      region-dependent manner. Its expression persisted in white matter, mainly in
      caudal corpus callosum, and the neurogenic subventricular zone for a longer time
      than in grey matter. Additionally, the phenotypes of the TREM2+ microglia also
      differ; expressing CD16/32, MHCII and CD86 (antigen presentation markers) and
      CD68 (phagocytic marker) in different regions as well as with different intensity
      till P7. The mannose receptor (CD206) colocalized with TREM2 only at P1-P3 in the
      subventricular zone and cingulum, while others persisted at low intensities till
      P7. Furthermore, the spatiotemporal expression pattern and characterization of
      TREM2 indicate towards its other plausible roles in phagocytosis, progenitor's
      fate determination or microglia phenotype modulation during postnatal
      development. Hence, the increase of TREM2 observed in pathologies may
      recapitulate their function during postnatal development, as a better
      understanding of this period may open new pathway for future therapies. 

PMID- 23977214
TI  - Angiostrongylus cantonensis (Nematode: Metastrongiloidea): in vitro cultivation
      of infective third-stage larvae to fourth-stage larvae.
AB  - The present study to attempt to cultivate Angiostrongylus cantonensis from third
      stage larvae (AcL3) to fourth-stage larvae (AcL4) in vitro in defined complete
      culture medium that contained with Minimum Essential Medium Eagle (MEM),
      supplemented amino acid (AA), amine (AM), fatty acid (FA), carbohydrate (CA) and
      20% fetal calf serum (FCS) was successful. When AcL3 were cultured in the defined
      complete culture medium at 37 degrees C in a 5% CO2 atmosphere, the larvae began
      to develop to AcL4 after 30 days of cultivation, and were enclosed within the
      sheaths of the third molts of the life cycle. Under these conditions, the larvae
      developed uniformly and reached to the fourth-stage 36 days. The morphology of
      AcL3 develop to AcL4 were recording and analyzing. Then comparison of A.
      cantonensis larval morphology and development between in vitro cultivation in
      defined complete culture medium and in vivo cultivation in infective BALB/c mice.
      The larvae that had been cultivated in vitro were smaller than AcL4 of infective
      BALB/c mice. However the AcL3 that were cultured using defined incomplete culture
      medium (MEM plus 20% FCS with AA+AM, FA, CA, AA+AM+FA, FA+CA, CA+AA+AM or not)
      did not adequately survive and develop. Accordingly, the inference is made that
      only the defined complete medium enable AcL3 develop to AcL4 in vitro. Some
      nematodes have been successfully cultured into mature worms but only a few
      researches have been made to cultivate A. cantonensis in vitro. The present study
      is the first to have succeeded in developing AcL3 to AcL4 by in vitro
      cultivation. Finally, the results of in vitro cultivation studies herein
      contribute to improving media for the effective development and growth of A.
      cantonensis. The gap in the A. cantonensis life cycle when the larvae are
      cultivated in vitro from third-stage larvae to fourth-stage larvae can thus be
      solved. 

PMID- 23977215
TI  - New continuous air pumping technique to improve clinical outcomes of descemet
      stripping automated endothelial keratoplasty in asian patients with previous
      ahmed glaucoma valve implantation.
AB  - BACKGROUND: To evaluate the outcomes of Descemet-stripping automated endothelial
      keratoplasty (DSAEK) with the use of continuous air pumping technique in Asian
      eyes with previous Ahmed glaucoma valve implantation. METHODS: The DSAEK
      procedure was modified in that complete air retention of the anterior chamber was
      maintained for 10 min using continuous air pumping at 30 mm Hg. The primary
      outcome measurement was graft survival, and postoperative clinical features
      including, rate of graft detachment, endothelial cell count, intraocular pressure
      (IOP), surgical time and cup/disc ratio were also recorded. RESULTS: A total of
      13 eyes of 13 patients which underwent modified DSAEK and 6 eyes of 6 patients
      which underwent conventional DSAEK were included. There was a significant
      difference in graft survival curves between two groups (P = 0.029); the 1-year
      graft survival rates were estimated as 100% and 66.7% for patients with modified
      DSAEK and those with traditional DSAEK, respectively. The rate of graft
      detachment were 0% and 33.3% for the modified DSAEK and conventional DSAEK
      groups, respectively (P = 0.088). The significantly lowered surgical time for air
      tamponade was noted in the modified DSAEK group compared to that in the
      conventional DSAEK group [median (IQR): 10.0 (10.0, 10.0) min vs. 24.5 (22.0,
      27.0) min; P<0.001] Postoperatively, patients in the modified DSAEK group had
      significantly lower IOP as compared to the conventional DSAEK group [12.0 (11.0,
      15.0) mm Hg vs. 16.0 (15.0, 18.0) mm Hg; P = 0.047]. Modified DSAEK patients had
      higher endothelial cell counts as compared to conventional DSAEK patients [2148.0
      (1964.0, 2218.0) vs. 1529.0 (713.0, 2014.0)], but the difference did not reach
      statistical significance (P = 0.072). CONCLUSIONS: New continuous air pumping
      technique in DSAEK can be performed safely and effectively in patients with prior
      GDDs placement who have corneal failure.

PMID- 23977216
TI  - Novel small-molecule AMP-activated protein kinase allosteric activator with
      beneficial effects in db/db mice.
AB  - AMP-activated protein kinase (AMPK) is an energy sensor of metabolism that is an
      attractive therapeutic target for type 2 diabetes mellitus and metabolic
      syndrome. Using a homogeneous scintillation proximity assay (SPA), we identified
      a new small-molecule AMPK activator, ZLN024, which allosterically stimulated
      active AMPK heterotrimers and the inactive alpha1 subunit truncations alpha1 (1
      394) and alpha1 (1-335) but not alpha1 (1-312). AMPK activation by ZLN024
      requires the pre-phosphorylation of Thr-172 by at least one upstream kinase and
      protects AMPK Thr-172 against dephosphorylation by PP2Calpha. ZLN024 activated
      AMPK in L6 myotubes and stimulated glucose uptake and fatty acid oxidation
      without increasing the ADP/ATP ratio. ZLN024 also activated AMPK in primary
      hepatocytes, decreased fatty acid synthesis and glucose output. Treatment of
      db/db mice with 15 mg/kg/day ZLN024 improved glucose tolerance; liver tissue
      weight, triacylglycerol and the total cholesterol content were decreased. The
      hepatic transcriptional level of G6Pase, FAS and mtGPAT were reduced. The
      transcription of genes involved in fatty acid oxidation and the mitochondrial
      biogenesis of muscle tissue were elevated. The ACC phosphorylation was increased
      in muscle and liver. This study provides a novel allosteric AMPK activator for
      functional study in vitro and in vivo and demonstrates that AMPK allosteric
      activators could be a promising therapeutic approach for type 2 diabetes mellitus
      and metabolic syndrome. 

PMID- 23977217
TI  - Routine endoscopy for esophageal cancer is suggestive for patients with oral,
      oropharyngeal and hypopharyngeal cancer.
AB  - BACKGROUND: This study attempted to reveal the incidence and risk of synchronous
      and metachronous esophageal cancer in subjects with oral, oropharyngeal and
      hypopharyngeal cancer based on a population-wide database in Taiwan. METHODS: We
      retrieved data for this cross-sectional study from the Taiwanese Longitudinal
      Health Insurance Database 2000. The study group included 2,965 subjects who had
      received their first-time diagnosis of oral/oropharyngeal/hypopharyngeal cancer
      in 2002~2009. We assigned the date of their first diagnosis of
      oral/oropharyngeal/hypopharyngeal cancer as the index date. We also randomly
      retrieved 29,650 comparison subjects matched with the study subjects in terms of
      gender and age group. We assigned their first medical utilization that occurred
      in the index year as the index date for the comparison group. We further
      performed a conditional logistic regression to investigate the association
      between esophageal cancer and oral cancer. RESULTS: Results showed that
      prevalences of esophageal cancer within 3 months before and after the index date
      were respectively 2.19% and 0.04% for the study and comparison groups. A
      conditional logistic regression revealed that the odds ratio (OR) of esophageal
      cancer for subjects with oral/oropharyngeal/hypopharyngeal cancer was 55.33 (95%
      confidence interval (CI): 29.86~102.52) compared to comparison subjects.
      Furthermore, compared to comparison subjects, ORs for esophageal cancer were
      respectively 18.41 (95% CI: 8.50-39.85), 40.49 (95% CI: 15.11~108.64), and 240.96
      (95% CI: 125.49-462.69) for study subjects with a malignancy of the oral cavity,
      oropharynx, and hypopharynx. CONCLUSION: We concluded that there were relatively
      high chances for synchronous and metachronous esophageal cancers being detected
      through panendoscopy in patients with oral, oropharyngeal, and hypopharyngeal
      cancers. The routine use of panendoscopy in such patients should be encouraged
      with a higher priority.

PMID- 23977218
TI  - A mid-life vitamin A supplementation prevents age-related spatial memory deficits
      and hippocampal neurogenesis alterations through CRABP-I.
AB  - Age-related memory decline including spatial reference memory is considered to
      begin at middle-age and coincides with reduced adult hippocampal neurogenesis.
      Moreover, a dysfunction of vitamin A hippocampal signalling pathway has been
      involved in the appearance of age-related memory deficits but also in adult
      hippocampal neurogenesis alterations. The present study aims at testing the
      hypothesis that a mid-life vitamin A supplementation would be a successful
      strategy to prevent age-related memory deficits. Thus, middle-aged Wistar rats
      were submitted to a vitamin A enriched diet and were tested 4 months later in a
      spatial memory task. In order to better understand the potential mechanisms
      mediating the effects of vitamin A supplementation on hippocampal functions, we
      studied different aspects of hippocampal adult neurogenesis and evaluated
      hippocampal CRABP-I expression, known to modulate differentiation processes.
      Here, we show that vitamin A supplementation from middle-age enhances spatial
      memory and improves the dendritic arborisation of newborn immature neurons
      probably resulting in a better survival and neuronal differentiation in aged
      rats. Moreover, our results suggest that hippocampal CRABP-I expression which
      controls the intracellular availability of retinoic acid (RA), may be an
      important regulator of neuronal differentiation processes in the aged
      hippocampus. Thus, vitamin A supplementation from middle-age could be a good
      strategy to maintain hippocampal plasticity and functions. 

PMID- 23977219
TI  - XRCC3 and RAD51 expression are associated with clinical factors in breast cancer.
AB  - AIMS: XRCC3 and RAD51 are two important members in homologous recombination
      repair pathway. This study was performed to detect the expressions of these two
      molecules in breast cancer and explore their correlations with
      clinicopathological factors. METHODS AND RESULTS: Immunohistochemistry was used
      to detect protein expressions of XRCC3 and RAD51 in 248 cases of breast cancer
      tissue and 78 cases of adjacent non-cancerous tissue. Data showed that
      expressions for both XRCC3 and RAD51 were significantly increased in breast
      cancer. High XRCC3 expression was associated with large tumor size and positive
      PR and HER2 status, while high RAD51 expression was associated with axillary
      lymph node metastasis and positive PR and HER2 status. The result of multivariate
      analysis demonstrated that HER2, PR and RAD51 were significantly association with
      XRCC3. And besides XRCC3, axillary lymph node metastasis and PR were
      significantly correlated with RAD51. CONCLUSIONS: XRCC3 and RAD51 were
      significantly associated with clinicopathological factors and they might play
      important roles in the development and progress of breast cancer.

PMID- 23977220
TI  - Monocyte chemoattractant protein-1 deficiency attenuates oxidative stress and
      protects against ovariectomy-induced chronic inflammation in mice.
AB  - BACKGROUND: Loss of ovarian function is highly associated with an elevated risk
      of metabolic disease. Monocyte chemoattractant protein-1 (MCP-1, C-C chemokine
      ligand 2) plays critical roles in the development of inflammation, but its role
      in ovariectomy (OVX)-induced metabolic disturbance has not been known.
      METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the role of MCP-1 in OVX
      induced metabolic perturbation using MCP-1-knockout mice. OVX increased fat mass,
      serum levels of MCP-1, macrophage-colony stimulating factor (M-CSF), and reactive
      oxygen species (ROS), whereas MCP-1 deficiency attenuated these. OVX-induced
      increases of visceral fat resulted in elevated levels of highly inflammatory
      CD11c-expressing cells as well as other immune cells in adipose tissue, whereas a
      lack of MCP-1 significantly reduced all of these levels. MCP-1 deficiency
      attenuated activation of phospholipase Cgamma2, transforming oncogene from Ak
      strain, and extracellular signal-regulated kinase as well as generation of ROS,
      which is required for up-regulating CD11c expression upon M-CSF stimulation in
      bone marrow-derived macrophages. CONCLUSIONS/SIGNIFICANCE: Our data suggested
      that MCP-1 plays a key role in developing metabolic perturbation caused by a loss
      of ovarian functions through elevating CD11c expression via ROS generation.

PMID- 23977221
TI  - Conceptual design and simulation study of an ROI-focused panel-PET scanner.
AB  - Positron emission tomography (PET) is an important imaging modality for clincial
      use. Conventionally, the PET scanner is generally built to provide a roomy enough
      transverse field-of-view (FOV) for imaging most adults' torsos. However, in many
      cases, the region-of-interest (ROI) for imaging is usually a small area inside
      the human body. Therefore, to fulfill a PET system which provides an FOV
      comparable in size to the target ROI seems appealing and more cost effective.
      Meanwhile, such a PET system has the potential for portable or bedside
      application with the reduced system size. In this work, we have investigated the
      feasibility of using dual-headed panel-detectors to build an ROI-focused PET
      scanner. A novel windowed list-mode ordered subset expectation maximization
      method was developed to perform the ROI image reconstruction. With this method,
      the ROI of the object can be reconstructed from the coincidences whose position
      determined by time-of-flight (TOF) measurements was inside the ROI. Monte Carlo
      simulation demonstrates the feasibility of detecting lesions not less than 1 cm
      in diameter, with a 300 ps full width at half maximum timing resolution. As a
      critical system performance, the impact of TOF information on image quality has
      been studied and the required TOF capability was assessed. With enhanced timing
      resolution, the distortions and artifacts were reduced effectively. The further
      improved TOF capability also shows a noticeable improvement of detection
      performance for low uptake lesions, as well as the recovery speed of lesion
      contrast, which is of practical significance in the lesion detection task. 

PMID- 23977222
TI  - The toll-like receptor agonist imiquimod is active against prions.
AB  - Using a yeast-based assay, a previously unsuspected antiprion activity was found
      for imiquimod (IQ), a potent Toll-like receptor 7 (TLR7) agonist already used for
      clinical applications. The antiprion activity of IQ was first detected against
      yeast prions [PSI (+) ] and [URE3], and then against mammalian prion both ex vivo
      in a cell-based assay and in vivo in a transgenic mouse model for prion diseases.
      In order to facilitate structure-activity relationship studies, we conducted a
      new synthetic pathway which provides a more efficient means of producing new IQ
      chemical derivatives, the activity of which was tested against both yeast and
      mammalian prions. The comparable antiprion activity of IQ and its chemical
      derivatives in the above life forms further emphasizes the conservation of prion
      controlling mechanisms throughout evolution. Interestingly, this study also
      demonstrated that the antiprion activity of IQ and IQ-derived compounds is
      independent from their ability to stimulate TLRs. Furthermore, we found that IQ
      and its active chemical derivatives inhibit the protein folding activity of the
      ribosome (PFAR) in vitro. 

PMID- 23977223
TI  - Implicit motivational impact of pictorial health warning on cigarette packs.
AB  - OBJECTIVE: The use of pictorial warning labels on cigarette packages is one of
      the provisions included in the first ever global health treaty by the World
      Health Organization against the tobacco epidemic. There is substantial evidence
      demonstrating the effectiveness of graphic health warning labels on intention to
      quit, thoughts about health risks and engaging in cessation behaviors. However,
      studies that address the implicit emotional drives evoked by such warnings are
      still underexplored. Here, we provide experimental data for the use of pictorial
      health warnings as a reliable strategy for tobacco control. METHODS: Experiment 1
      pre-tested nineteen prototypes of pictorial warnings to screen for their
      emotional impact. Participants (n = 338) were young adults balanced in gender,
      smoking status and education. Experiment 2 (n = 63) tested pictorial warnings
      (ten) that were stamped on packs. We employed an innovative set-up to investigate
      the impact of the warnings on the ordinary attitude of packs' manipulation, and
      quantified judgments of warnings' emotional strength and efficacy against
      smoking. FINDINGS: Experiment 1 revealed that women judged the warning prototypes
      as more aversive than men, and smokers judged them more aversive than non
      smokers. Participants with lower education judged the prototypes more aversive
      than participants with higher education. Experiment 2 showed that stamped
      warnings antagonized the appeal of the brands by imposing a cost to manipulate
      the cigarette packs, especially for smokers. Additionally, participants'
      judgments revealed that the more aversive a warning, the more it is perceived as
      effective against smoking. CONCLUSIONS: Health warning labels are one of the key
      components of the integrated approach to control the global tobacco epidemic. The
      evidence presented in this study adds to the understanding of how implicit
      responses to pictorial warnings may contribute to behavioral change.

PMID- 23977224
TI  - Mitochondria are the target organelle of differentiation-inducing factor-3, an
      anti-tumor agent isolated from Dictyostelium discoideum [corrected].
AB  - Differentiation-inducing factor-3 (DIF-3), found in the cellular slime mold
      Dictyostelium discoideum, and its derivatives such as butoxy-DIF-3 (Bu-DIF-3) are
      potent anti-tumor agents. However, the precise mechanisms underlying the actions
      of DIF-3 remain to be elucidated. In this study, we synthesized a green
      fluorescent derivative of DIF-3, BODIPY-DIF-3, and a control fluorescent
      compound, Bu-BODIPY (butyl-BODIPY), and investigated how DIF-like molecules
      behave in human cervical cancer HeLa cells by using both fluorescence and
      electron microscopy. BODIPY-DIF-3 at 5-20 u M suppressed cell growth in a dose
      dependent manner, whereas Bu-BODIPY had minimal effect on cell growth. When cells
      were incubated with BODIPY-DIF-3 at 20 uM, it penetrated cell membranes within
      0.5 h and localized mainly in mitochondria, while Bu-BODIPY did not stain the
      cells. Exposure of cells for 1-3 days to DIF-3, Bu-DIF-3, BODIPY-DIF-3, or CCCP
      (a mitochondrial uncoupler) induced substantial mitochondrial swelling,
      suppressing cell growth. When added to isolated mitochondria, DIF-3, Bu-DIF-3,
      and BOIDPY-DIF-3, like CCCP, dose-dependently promoted the rate of oxygen
      consumption, but Bu-BODIPY did not. Our results suggest that these bioactive DIF
      like molecules suppress cell growth, at least in part, by disturbing
      mitochondrial activity. This is the first report showing the cellular
      localization and behavior of DIF-like molecules in mammalian tumor cells. 

PMID- 23977225
TI  - Low ABCB1 gene expression is an early event in colorectal carcinogenesis.
AB  - The ABCB1/MDR1 gene product ABCB1/P-glycoprotein is implicated in the development
      of colorectal cancer (CRC). NFKB1 encodes transcription factors regulating
      expression of a number of genes including ABCB1. We have previously found
      association between the ABCB1 C-rs3789243-T polymorphism and CRC risk and
      interactions between the ABCB1 C-rs3789243-T and C3435T polymorphisms and meat
      intake in relation to CRC risk (Andersen, BMC Cancer, 2009, 9, 407). ABCB1 and
      NFKB1 mRNA levels were assessed in intestinal tissue from 122 CRC cases, 101
      adenoma cases (12 with severe dysplasia, 89 with mild-moderate dysplasia) and
      from 18 healthy individuals, together with gene polymorphisms in ABCB1 and NFKB1.
      ABCB1 mRNA levels were highest in the healthy individuals and significantly lower
      in mild/moderate and severe dysplasia tissue (P<0.05 for both), morphologically
      normal tissues close to the tumour (P<0.05), morphologically normal tissue at a
      distance from the tumour (P<0.05) and CRC tissue (P<0.001). Furthermore, ABCB1
      mRNA levels were lower in adenomas and carcinomas compared to morphologically
      normal tissue from the same individuals (P<0.01). The ABCB1 C-rs3789243-T and
      NFKB1 -94ins/del homozygous variant genotypes were associated with low ABCB1 mRNA
      levels in morphologically normal sigmoid tissue from adenoma cases (P<0.05 for
      both). NFKB1 mRNA levels were lower in both tumour and normal tissue from cancer
      patients (P<0.001) as compared to healthy individuals but we were unable to show
      association between NFKB1 -94ins/del genotype and NFKB1 mRNA levels. This study
      suggests that low ABCB1 mRNA levels are an early event in CRC development and
      that the two polymorphisms affect ABCB1 mRNA levels whereas low NFKB1 mRNA levels
      occur later in carcinogenesis. Low ABCB1 protein levels may promote colorectal
      carcinogenesis through increasing intracellular exposure to carcinogenic ABCB1
      substrates. 

PMID- 23977226
TI  - Matrix metalloproteinase-9 inhibition improves proliferation and engraftment of
      myogenic cells in dystrophic muscle of mdx mice.
AB  - Duchenne muscular dystrophy (DMD) caused by loss of cytoskeletal protein
      dystrophin is a devastating disorder of skeletal muscle. Primary deficiency of
      dystrophin leads to several secondary pathological changes including fiber
      degeneration and regeneration, extracellular matrix breakdown, inflammation, and
      fibrosis. Matrix metalloproteinases (MMPs) are a group of extracellular proteases
      that are involved in tissue remodeling, inflammation, and development of
      interstitial fibrosis in many disease states. We have recently reported that the
      inhibition of MMP-9 improves myopathy and augments myofiber regeneration in mdx
      mice (a mouse model of DMD). However, the mechanisms by which MMP-9 regulates
      disease progression in mdx mice remain less understood. In this report, we
      demonstrate that the inhibition of MMP-9 augments the proliferation of satellite
      cells in dystrophic muscle. MMP-9 inhibition also causes significant reduction in
      percentage of M1 macrophages with concomitant increase in the proportion of
      promyogenic M2 macrophages in mdx mice. Moreover, inhibition of MMP-9 increases
      the expression of Notch ligands and receptors, and Notch target genes in skeletal
      muscle of mdx mice. Furthermore, our results show that while MMP-9 inhibition
      augments the expression of components of canonical Wnt signaling, it reduces the
      expression of genes whose products are involved in activation of non-canonical
      Wnt signaling in mdx mice. Finally, the inhibition of MMP-9 was found to
      dramatically improve the engraftment of transplanted myoblasts in skeletal muscle
      of mdx mice. Collectively, our study suggests that the inhibition of MMP-9 is a
      promising approach to stimulate myofiber regeneration and improving engraftment
      of muscle progenitor cells in dystrophic muscle. 

PMID- 23977227
TI  - The nitrate transporter (NRT) gene family in poplar.
AB  - Nitrate is an important nutrient required for plant growth. It also acts as a
      signal regulating plant development. Nitrate is actively taken up and transported
      by nitrate transporters (NRT), which form a large family with many members and
      distinct functions. In contrast to Arabidopsis and rice there is little
      information about the NRT family in woody plants such as Populus. In this study,
      a comprehensive analysis of the Populus NRT family was performed. Sixty-eight
      PtNRT1/PTR, 6 PtNRT2, and 5 PtNRT3 genes were identified in the P. trichocarpa
      genome. Phylogenetic analysis confirmed that the genes of the NRT family are
      divided into three clades: NRT1/PTR with four subclades, NRT2, and NRT3.
      Topological analysis indicated that all members of PtNRT1/PTR and PtNRT2 have 8
      to 12 trans-membrane domains, whereas the PtNRT3 proteins have no or up to two
      trans-membrane domains. Four PtNRT3 members were predicted as secreted proteins.
      Microarray analyses revealed tissue-specific expression patterns of PtNRT genes
      with distinct clusters of NRTs for roots, for the elongation zone of the apical
      stem segment and the developing xylem and a further cluster for leaves, bark and
      wood. A comparison of different poplar species (P. trichocarpa, P. tremula, P.
      euphratica, P. fremontii x P. angustifolia, and P. x canescens) showed that the
      tissue-specific patterns of the NRT genes varied to some extent with species.
      Bioinformatic analysis of putative cis-regulatory elements in the promoter
      regions of PtNRT family retrieved motifs suggesting the regulation of the NRT
      genes by N metabolism, by energy and carbon metabolism, and by phytohormones and
      stress. Multivariate analysis suggested that the combination and abundance of
      motifs in distinct promoters may lead to tissue-specificity. Our genome wide
      analysis of the PtNRT genes provides a valuable basis for functional analysis
      towards understanding the role of nitrate transporters for tree growth. 

PMID- 23977228
TI  - Raman microspectroscopy analysis in the treatment of acanthamoeba keratitis.
AB  - Acanthamoeba keratitis is a rare but serious corneal disease, often observed in
      contact lens wearers. Clinical treatment of infected patients frequently involves
      the use of polyhexamethylene biguanide (PHMB), a polymer used as a disinfectant
      and antiseptic, which is toxic also for the epithelial cells of the cornea.
      Prompt and effective diagnostic tools are hence highly desiderable for both
      starting early therapy and timely suspension of the treatment. In this work we
      use Raman microspectroscopy to analyse in vitro a single Acanthamoeba cell in
      cystic phase. In particular, we investigate the effect of PHMB at the single-cell
      level, providing useful information on both the underlying biochemical mechanism
      and the time frame for Acanthamoeba eradication in ocular infections.
      Furthermore, we demonstrate that Raman spectroscopy, in conjunction with standard
      multivariate analysis methods, allows discriminating between live and dead
      Acanthamoebas, which is fundamental to optimizing patients' treatment. 

PMID- 23977229
TI  - Cardioembolic and small vessel disease stroke show differences in associations
      between systemic C3 levels and outcome.
AB  - BACKGROUND: Activation of the complement system has been proposed to play a role
      in the pathophysiology of stroke. As the specific involvement of the complement
      proteins may be influenced by stroke etiology, we compared plasma C3 and C3a
      levels in patients with cardioembolic (CE) and small vessel disease (SVD)
      subtypes of ischemic stroke and control subjects and evaluated their association
      to outcome at three months and two years. METHODOLOGY/PRINCIPAL FINDINGS: Plasma
      C3 and C3a levels in 79 CE and 79 SVD stroke patients, sampled within 10 days and
      at three months after stroke, and age- and sex-matched control subjects from The
      Sahlgrenska Academy Study on Ischemic Stroke were measured by ELISA. Functional
      outcome was assesed with modified Rankin Scale. In the CE group, plasma C3 levels
      were elevated only in the acute phase, whereas C3a was elevated at both time
      points. The follow-up phase plasma C3 levels in the upper third were associated
      with an increased risk of unfavorable outcome at three months (OR 7.12, CI 1.72
      29.46, P = 0.007) as well as after two years (OR 8.25, CI 1.61-42.28, P = 0.011)
      after stroke. These associations withstand adjustment for age and sex.
      Conversely, three-month follow-up plasma C3a/C3 level ratios in the middle third
      were associated with favorable outcome after two years both in the univariate
      analysis (OR 0.19, CI 0.05-0.82, P = 0.026) and after adjustment for age and sex
      (OR 0.19, CI 0.04-0.88, P = 0.033). In the SVD group, plasma C3 and C3a levels
      were elevated at both time points but showed no significant associations with
      outcome. CONCLUSIONS: Plasma C3 and C3a levels are elevated after CE and SVD
      stroke but show associations with outcome only in CE stroke.

PMID- 23977230
TI  - Size of gene specific inverted repeat--dependent gene deletion In Saccharomyces
      cerevisiae.
AB  - We describe here an approach for rapidly producing scar-free and precise gene
      deletions in S. cerevisiae with high efficiency. Preparation of the disruption
      gene cassette in this approach was simply performed by overlap extension-PCR of
      an invert repeat of a partial or complete sequence of the targeted gene with
      URA3. Integration of the prepared disruption gene cassette to the designated
      position of a target gene leads to the formation of a mutagenesis cassette within
      the yeast genome, which consists of a URA3 gene flanked by the targeted gene and
      its inverted repeat between two short identical direct repeats. The inherent
      instability of the inverted sequences in close proximity facilitates the self
      excision of the entire mutagenesis cassette deposited in the genome and promotes
      homologous recombination resulting in a seamless deletion via a single
      transformation. This rapid assembly circumvents the difficulty during preparation
      of disruption gene cassettes composed of two inverted repeats of the URA3, which
      requires the engineering of unique restriction sites for subsequent digestion and
      T4 DNA ligation in vitro. We further identified that the excision of the entire
      mutagenesis cassette flanked by two DRs in the transformed S. cerevisiae is
      dependent on the length of the inverted repeat of which a minimum of 800 bp is
      required for effective gene deletion. The deletion efficiency improves with the
      increase of the inverted repeat till 1.2 kb. Finally, the use of gene-specific
      inverted repeats of target genes enables simultaneous gene deletions. The
      procedure has the potential for application on other yeast strains to achieve
      precise and efficient removal of gene sequences. 

PMID- 23977231
TI  - S100A8 and S100A9 induce cytokine expression and regulate the NLRP3 inflammasome
      via ROS-dependent activation of NF-kappaB(1.).
AB  - S100A8 and S100A9 are cytoplasmic proteins expressed by phagocytes. High
      concentrations of these proteins have been correlated with various inflammatory
      conditions, including autoimmune diseases such as rheumatoid arthritis and
      Crohn's disease, as well as autoinflammatory diseases. In the present study, we
      examined the effects of S100A8 and S100A9 on the secretion of cytokines and
      chemokines from PBMCs. S100A8 and S100A9 induced the secretion of cytokines such
      as IL-6, IL-8, and IL-1beta. This secretion was associated with the activation
      and translocation of the transcription factor NF-kappaB. Inhibition studies using
      antisense RNA and the pharmacological agent BAY-117082 confirmed the involvement
      of NF-kappaB in IL-6, IL-8, and IL-1beta secretion. S100A8- and S100A9-mediated
      activation of NF-kappaB, the NLR family, pyrin domain-containing 3 (NLRP3)
      protein, and pro-IL-1beta expression was dependent on the generation of reactive
      oxygen species. This effect was synergistically enhanced by ATP, a known
      inflammasome activator. These results suggest that S100A8 and S100A9 enhance the
      inflammatory response by inducing cytokine secretion of PBMCs. 

PMID- 23977232
TI  - The clinical relevance of pre-formed anti-HLA and anti-MICA antibodies after cord
      blood transplantation in children.
AB  - Preformed anti-HLA antibodies (AHA) are known to be associated with delayed
      engraftment and reduced overall survival after adult hematopoietic stem cell
      transplantation. However, limited data is available in pediatric patients. In
      this study, we explored the role of AHA on clinical outcomes in 70 pediatric
      patients who received a single unit of HLA mismatch cord blood for hematologic
      malignancies, immunodeficiencies or metabolic diseases. The presence of AHA was
      detected in 44% (31/70) of the patients. Preformed class I AHA was associated
      with an increased occurrence of grade 1-4 acute graft-versus host disease
      (p<0.05). The presence of anti- major-histocompatibility-complex class I-related
      chain A antigens (MICA) antibodies was significantly associated with a reduced
      platelet recovery after transplantation (p<0.05). AHA of class II with the
      strength of antibody titer measured as the mean fluorescence intensity above 2000
      was associated with reduced event-free survival (p<0.05). A reduction of high
      titer of AHA and anti-MICA antibodies might have to be considered before cord
      blood transplantation in pediatric patients for better outcomes. 

PMID- 23977233
TI  - Alcohol consumption and viral load are synergistically associated with CIN1.
AB  - PURPOSE: We investigated the association between alcohol consumption and risk of
      cervical intraepithelial neoplasia (CIN) and cervical cancer, and determined
      whether these associations were modified by human papillomavirus (HPV) viral load
      in high-risk HPV-positive women participating in the Korean HPV cohort study
      (KHPV). METHODS: Among the women recruited in the KHPV (n = 1,243) from March
      2006 to December 2009, we analyzed normal cytology (n = 581) as control group,
      CIN1 (n = 299), CIN2/3 (n = 161), or cervical cancer (n = 202). Multinomial
      logistic analysis was performed to estimate multivariate-adjusted odds ratios
      (OR). RESULTS: Alcohol drinkers had an increased risk of CIN1 (OR = 2.18, 95% CI
      1.22-3.89) compared with non-drinkers after adjusting for potential confounders.
      Subjects with more frequent alcohol consumption had a higher risk of CIN1 (p for
      linear trend <0.0001). Higher ethanol consumption was associated with an
      increased risk of CIN1 (p for linear trend = 0.0001). We also observed a
      synergistic effect between HPV viral load and alcohol consumption: drinkers with
      a high HPV viral load (>=100 RLU/PC) were associated with a significantly
      increased risk of CIN1 (OR = 19.1; 95% CI, 6.60-55.3, interaction p<0.001). There
      were no associations between alcohol drinking and CIN2/3 or cervical cancer.
      CONCLUSIONS: HPV viral load and alcohol was associated with the risk of CIN1
      among high-risk HPV-positive women. This is the first demonstration that alcohol
      is an independent and combined risk factor of CIN1.

PMID- 23977234
TI  - A BAP1 mutation in a Danish family predisposes to uveal melanoma and other
      cancers.
AB  - Truncating germline mutations in the tumor suppressor gene BRCA-1 associated
      protein-1 (BAP1) have been reported in families predisposed to developing a wide
      range of different cancer types including uveal melanoma and cutaneous melanoma.
      There has also been an association between amelanotic tumor development and
      germline BAP1 mutation suggesting a possible phenotypic characteristic of BAP1
      mutation carriers. Though there have been many types of cancer associated with
      germline BAP1 mutation, the full spectrum of disease association is yet to be
      ascertained. Here we describe a Danish family with predominantly uveal melanoma
      but also a range of other tumor types including lung, neuroendocrine, stomach,
      and breast cancer; as well as pigmented skin lesions. Whole-exome sequencing
      identified a BAP1 splice mutation located at c.581-2A>G, which leads to a
      premature truncation of BAP1 in an individual with uveal melanoma. This mutation
      was carried by several other family members with melanoma or various cancers. The
      finding expands on the growing profile of BAP1 as an important uveal and
      cutaneous melanoma tumor suppressor gene and implicates its involvement in the
      development of lung, and stomach cancer. 

PMID- 23977235
TI  - Reduced expression of Enac in Placenta tissues of patients with severe
      preeclampsia is related to compromised trophoblastic cell migration and invasion
      during pregnancy.
AB  - The purpose of the study is to investigate the expression of epithelial sodium
      channel (ENaC) in normal pregnancy and severe preeclampsia placenta and to
      explore the underlying mechanism of the relationship between the altered ENaC
      expression and onset of preeclampsia. Reverse transcription polymerase chain
      reaction (RT-PCR) and Western blot were used to check epithelial sodium channel
      subunits expression in mRNA and protein level in first term and full term
      placental tissue. ENaCalpha specific RNAi were used to knockdown ENaC expression
      and cell invasion and migration assay were used to check whether reduced
      expression of ENaC can compromise trophoblast cell function. The result showed
      that ENaCalpha was highly expressed in first term placental trophoblast cells;
      while EnaCbeta was highly expressed in full term placenta. Knockdown ENaCalpha
      expression by using small interfering RNA reduced the invasive and migration
      abilities of HTR-8/SVneo cell. Real time-PCR and Western blot analysis showed
      that the expression levels of ENaCbeta were also significantly lower in severe
      preeclampsia compared with normal pregnancy. It is concluded that the ENaC played
      an important role in trophoblast cell invasion and migration. Reduced expression
      and activity of epithelial sodium channel in trophoblast cells may be involved in
      the pathogenesis of preeclampsia. 

PMID- 23977236
TI  - Quantitative assessment of common genetic variants on chromosome 5p12 and hormone
      receptor status with breast cancer risk.
AB  - Several genome-wide association studies on breast cancer (BC) have reported
      similar findings of a new susceptibility locus, 5p12. After that, a number of
      studies reported that the rs10941679, rs4415084, and rs981782 polymorphism in
      chromosome 5p12 has been implicated in BC risk. However, the studies have yielded
      contradictory results. To derive a more precise estimation of the relationship, a
      meta-analysis of 131,983 BC cases and 200,314 controls from 24 published case
      control studies was performed. Overall, significantly elevated BC risk was
      associated with rs10941679, rs4415084, and rs981782 risk allele when all studies
      were pooled into the meta-analysis. In the subgroup analysis by ethnicity,
      significantly increased risks were found for the rs10941679 and rs4415084
      polymorphism among Caucasians and East Asians, while no significant associations
      were observed for the two polymorphisms in African and other ethnic populations.
      For 5p12-rs981782, significant associations were only detected among Caucasians.
      In addition, we found that rs10941679 and rs4415084 on 5p12 confer risk,
      exclusively for estrogen receptor (ER)-positive tumors with per-allele OR of 1.16
      (95% CI: 1.11-1.21; P<10(-5)) and of 1.14 (95% CI: 1.09-1.19; P<10(-5))
      respectively. Ethnicity was identified as a potential source of between-study
      heterogeneity. In conclusion, this meta-analysis demonstrated that common
      variations are a risk factor associated with increased BC susceptibility, but
      these associations vary in different ethnic populations. 

PMID- 23977237
TI  - Antagonistic TNF receptor one-specific antibody (ATROSAB): receptor binding and
      in vitro bioactivity.
AB  - BACKGROUND: Selective inhibition of TNFR1 signaling holds the potential to
      greatly reduce the pro-inflammatory activity of TNF, while leaving TNFR2
      untouched, thus allowing for cell survival and tissue homeostasis. ATROSAB is a
      humanized antagonistic anti-TNFR1 antibody developed for the treatment of
      inflammatory diseases. METHODOLOGY/PRINCIPAL FINDINGS: The epitope of ATROSAB
      resides in the N-terminal region of TNFR1 covering parts of CRD1 and CRD2. By
      site-directed mutagenesis, we identified Arg68 and His69 of TNFR1 as important
      residues for ATROSAB binding. ATROSAB inhibited binding of (125)I-labeled TNF to
      HT1080 in the subnanomolar range. Furthermore, ATROSAB inhibited release of IL-6
      and IL-8 from HeLa and HT1080 cells, respectively, induced by TNF or lymphotoxin
      alpha (LTalpha). Different from an agonistic antibody (Htr-9), which binds to a
      region close to the ATROSAB epitope but elicits strong TNFR1 activation, ATROSAB
      showed a negligible induction of IL-6 and IL-8 production over a broad
      concentration range. We further verified that ATROSAB, comprising mutations
      within the Fc region known to abrogate complement fixation and antibody-mediated
      cellular effector functions, indeed lacks binding activity for C1q, FcgammaRI
      (CD64), FcgammaRIIB (CD32b), and FcgammaRIII (CD16) disabling ADCC and CDC.
      CONCLUSIONS/SIGNIFICANCE: The data corroborate ATROSAB's unique function as a
      TNFR1-selective antagonist efficiently blocking both TNF and LTalpha action. In
      agreement with recent studies of TNFR1 complex formation and activation, we
      suggest a model of the underlying mechanism of TNFR1 inhibition by ATROSAB.

PMID- 23977238
TI  - In vivo delivery of adenoviral vector containing interleukin-17 receptor a
      reduces cardiac remodeling and improves myocardial function in viral myocarditis
      leading to dilated cardiomyopathy.
AB  - Th17 cells have been implicated in the pathogenesis of myocarditis. Interleukin
      (IL)-17A produced by Th17 cells is dispensable for viral myocarditis but
      essential for the progression to dilated cardiomyopathy (DCM). This study
      investigated whether the adenoviral transfer of the IL-17 receptor A reduces
      myocardial remodeling and dysfunction in viral myocarditis leading to DCM. In a
      mouse model of Coxsackievirus B3 (CVB3)-induced chronic myocarditis, the delivery
      of the adenovirus-containing IL-17 receptor A (Ad-IL17RA:Fc) reduced IL-17A
      production and decreased the number of Th17 cells in the spleen and heart,
      leading to the down-regulation of systemic TNF-alpha and IL-6 production. Cardiac
      function improved significantly in the Ad-IL17R:Fc- compared with the Ad-null
      treated mice 3 months after the first CVB3 infection. Ad-IL17R:Fc reduced the
      left ventricle dilation and decreased the mortality in viral myocarditis, leading
      to DCM (56% in the Ad-IL17R:Fc versus 76% in the Ad-null group). The protective
      effects of Ad-IL17R-Fc on remodeling correlated with the attenuation of
      myocardial collagen deposition and the reduction of fibroblasts in CVB3-infected
      hearts, which was accompanied by the down-regulation of A distintegrin and
      metalloprotease with thrombospondin type 1 motifs (ADAMTS-1), Matrix
      metalloproteinase-2(MMP-2), and collagen subtypes I and III in the heart.
      Moreover, in cultured cardiac fibroblasts, IL-17A induced the expression of
      ADAMTS-1, MMP-2, and collagen subtypes I and III and increased the proliferation
      of fibroblasts. We determined that the delivery of IL-17-RA:Fc reduces cardiac
      remodeling, improves function, and decreases mortality in viral myocarditis
      leading to DCM, possibly by suppressing fibrosis. Therefore, the adenoviral
      transfer of the IL-17 receptor A may represent an alternative therapy for chronic
      viral myocarditis and its progression to DCM. 

PMID- 23977239
TI  - Default-mode network changes in Huntington's disease: an integrated MRI study of
      functional connectivity and morphometry.
AB  - Previous MRI studies of functional connectivity in pre-symptomatic mutation
      carriers of Huntington's disease (HD) have shown dysfunction of the Default-Mode
      Network (DMN). No data however are currently available on the DMN alterations in
      the symptomatic stages of the disease, which are characterized by cortical
      atrophy involving several DMN nodes. We assessed DMN integrity and its possible
      correlations with motor and cognitive symptoms in 26 symptomatic HD patients as
      compared to 22 normal volunteers, by analyzing resting state functional MRI data,
      using the Precuneal Cortex/Posterior Cingulate Cortices (PC/PCC) as seed,
      controlling at voxel level for the effect of atrophy by co-varying for gray
      matter volume. Direct correlation with PC/PCC was decreased, without correlation
      with atrophy, in the ventral medial prefrontal cortex (including anterior
      cingulate and subgenual cortex), right dorso-medial prefrontal cortex, and in the
      right inferior parietal cortex (mainly involving the angular gyrus). Negative
      correlations with PC/PCC were decreased bilaterally in the inferior parietal
      cortices, while a cluster in the right middle occipital gyrus presented increased
      correlation with PC/PCC. DMN changes in the ventral medial prefrontal cortex
      significantly correlated with the performance at the Stroop test (p = .0002).
      Widespread DMN changes, not correlating with the atrophy of the involved nodes,
      are present in symptomatic HD patients, and correlate with cognitive
      disturbances.

PMID- 23977240
TI  - New insights into somatic embryogenesis: leafy cotyledon1, baby boom1 and WUSCHEL
      related homeobox4 are epigenetically regulated in Coffea canephora.
AB  - Plant cells have the capacity to generate a new plant without egg fertilization
      by a process known as somatic embryogenesis (SE), in which differentiated somatic
      cells can form somatic embryos able to generate a functional plant. Although
      there have been advances in understanding the genetic basis of SE, the epigenetic
      mechanism that regulates this process is still unknown. Here, we show that the
      embryogenic development of Coffea canephora proceeds through a crosstalk between
      DNA methylation and histone modifications during the earliest embryogenic stages
      of SE. We found that low levels of DNA methylation, histone H3 lysine 9
      dimethylation (H3K9me2) and H3K27me3 change according to embryo development.
      Moreover, the expression of LEAFY cotyledon1 (LEC1) and BABY BOOM1 (BBM1) are
      only observed after SE induction, whereas WUSCHEL-related homeobox4 (WOX4)
      decreases its expression during embryo maturation. Using a pharmacological
      approach, it was found that 5-Azacytidine strongly inhibits the embryogenic
      response by decreasing both DNA methylation and gene expression of LEC1 and BBM1.
      Therefore, in order to know whether these genes were epigenetically regulated, we
      used Chromatin Immunoprecipitation (ChIP) assays. It was found that WOX4 is
      regulated by the repressive mark H3K9me2, while LEC1 and BBM1 are epigenetically
      regulated by H3K27me3. We conclude that epigenetic regulation plays an important
      role during somatic embryogenic development, and a molecular mechanism for SE is
      proposed.

PMID- 23977241
TI  - SORLA-mediated trafficking of TrkB enhances the response of neurons to BDNF.
AB  - Stimulation of neurons with brain-derived neurotrophic factor (BDNF) results in
      robust induction of SORLA, an intracellular sorting receptor of the VPS10P domain
      receptor gene family. However, the relevance of SORLA for BDNF-induced neuronal
      responses has not previously been investigated. We now demonstrate that SORLA is
      a sorting factor for the tropomyosin-related kinase receptor B (TrkB) that
      facilitates trafficking of this BDNF receptor between synaptic plasma membranes,
      post-synaptic densities, and cell soma, a step critical for neuronal signal
      transduction. Loss of SORLA expression results in impaired neuritic transport of
      TrkB and in blunted response to BDNF in primary neurons; and it aggravates
      neuromotoric deficits caused by low BDNF activity in a mouse model of
      Huntington's disease. Thus, our studies revealed a key role for SORLA in
      mediating BDNF trophic signaling by regulating the intracellular location of
      TrkB. 

PMID- 23977242
TI  - Response of phytoplankton photophysiology to varying environmental conditions in
      the Sub-Antarctic and Polar Frontal Zone.
AB  - Climate-driven changes are expected to alter the hydrography of the Sub-Antarctic
      Zone (SAZ) and Polar Frontal Zone (PFZ) south of Australia, in which distinct
      regional environments are believed to be responsible for the differences in
      phytoplankton biomass in these regions. Here, we report how the dynamic
      influences of light, iron and temperature, which are responsible for the
      photophysiological differences between phytoplankton in the SAZ and PFZ,
      contribute to the biomass differences in these regions. High effective
      photochemical efficiency of photosystem II (F'(q)/F'(m)0.4), maximum
      photosynthesis rate (P(B)(max)), light-saturation intensity (E(k)), maximum rate
      of photosynthetic electron transport (1/[Symbol: see text]PSII), and low
      photoprotective pigment concentrations observed in the SAZ correspond to high
      chlorophyll a and iron concentrations. In contrast, phytoplankton in the PFZ
      exhibits low F'(q)/F'(M) (~ 0.2) and high concentrations of photoprotective
      pigments under low light environment. Strong negative relationships between iron,
      temperature, and photoprotective pigments demonstrate that cells were producing
      more photoprotective pigments under low temperature and iron conditions, and are
      responsible for the low biomass and low productivity measured in the PFZ. As
      warming and enhanced iron input is expected in this region, this could probably
      increase phytoplankton photosynthesis in this region. However, complex
      interactions between the biogeochemical processes (e.g. stratification caused by
      warming could prevent mixing of nutrients), which control phytoplankton biomass
      and productivity, remain uncertain.

PMID- 23977243
TI  - Control costs, enhance quality, and increase revenue in three top general public
      hospitals in Beijing, China.
AB  - BACKGROUND: With market-oriented economic and health-care reform, public
      hospitals in China have received unprecedented pressures from governmental
      regulations, public opinions, and financial demands. To adapt the changing
      environment and keep pace of modernizing healthcare delivery system, public
      hospitals in China are expanding clinical services and improving delivery
      efficiency, while controlling costs. Recent experiences are valuable lessons for
      guiding future healthcare reform. Here we carefully study three teaching
      hospitals, to exemplify their experiences during this period. METHODS: We
      performed a systematic analysis on hospitalization costs, health-care quality and
      delivery efficiencies from 2006 to 2010 in three teaching hospitals in Beijing,
      China. The analysis measured temporal changes of inpatient cost per stay (CPS),
      cost per day (CPD), inpatient mortality rate (IMR), and length of stay (LOS),
      using a generalized additive model. FINDINGS: There were 651,559 hospitalizations
      during the period analyzed. Averaged CPS was stable over time, while averaged CPD
      steadily increased by 41.7% (P<0.001), from CNY 1,531 in 2006 to CNY 2,169 in
      2010. The increasing CPD seemed synchronous with the steady rising of the
      national annual income per capita. Surgical cost was the main contributor to the
      temporal change of CPD, while medicine and examination costs tended to be stable
      over time. From 2006 and 2010, IMR decreased by 36%, while LOS reduced by 25%.
      Increasing hospitalizations with higher costs, along with an overall stable CPS,
      reduced IMR, and shorter LOS, appear to be the major characteristics of these
      three hospitals at present. INTERPRETATIONS: These three teaching hospitals have
      gained some success in controlling costs, improving cares, adopting modern
      medical technologies, and increasing hospital revenues. Effective hospital
      governance and physicians' professional capacity plus government regulations and
      supervisions may have played a role. However, purely market-oriented health-care
      reform could also misguide future healthcare reform.

PMID- 23977244
TI  - The diverse distribution of risk factors between breast cancer subtypes of ER, PR
      and HER2: a 10-year retrospective multi-center study in China.
AB  - INTRODUCTION: Hormone receptors, human epidermal growth factor receptor 2 and
      some risk factors determine therapies and prognosis of breast cancer. The risk
      factors distributed differently between patients with receptors. This study aimed
      to investigate the distribution of risk factors between subtypes of breast cancer
      by the 3 receptors in Chinese native women with a large sample size. METHODS: The
      multi-center study analyzed 4211 patient medical records from 1999 to 2008 in 7
      regions of China. Data on patients' demographic information, risk factors
      (menopausal status, parity, body mass index) and receptor statuses were
      extracted. Breast cancer subtypes included ER (+/-), PR (+/-), HER2 (+/-), 4
      ER/PR and 4 molecular subtypes. Wilcoxon and Chi-square tests were used to
      estimate the difference. The unconditional logistic regression model was used for
      analysis, and presented p-value after Bonferroni correction in the results.
      RESULTS: Compared to patients with negative progesterone receptor, the positive
      patients were younger at diagnosis, and reported less likely in postmenopausal
      status and lower parity (p<0.05). Comparing with the subtype of ER+/PR+, ER+/PR-
      subtype were 4-year older at diagnosis (OR = 1.02), more likely to be
      postmenopausal (OR = 1.91) and more likely to have >1 parity (OR = 1.36)
      (p<0.05); ER-/PR- subtype were more likely to be postmenopausal (OR = 1.33) and
      have >1 parity (OR = 1.19) (p<0.05). In contrast to the luminal A subtype, triple
      negative subtype had a lower BMI (OR = 0.96) and ORs of overweight and obesity
      reduced by >20% (p<0.05). CONCLUSION: In this study, it was found that Chinese
      female patients did have statistically significant differences of age, menopausal
      status, parity and body mass index between breast cancer subtypes. Studies are
      warranted to further investigate the risk factors between subtypes, which was
      meaningful for prevention and treatment among Chinese females.

PMID- 23977245
TI  - The amyloid precursor protein (APP) does not have a ferroxidase site in its E2
      domain.
AB  - The ubiquitous 24-meric iron-storage protein ferritin and multicopper oxidases
      such as ceruloplasmin or hephaestin catalyze oxidation of Fe(II) to Fe(III),
      using molecular oxygen as oxidant. The ferroxidase activity of these proteins is
      essential for cellular iron homeostasis. It has been reported that the amyloid
      precursor protein (APP) also has ferroxidase activity. The activity is assigned
      to a ferroxidase site in the E2 domain of APP. A synthetic 22-residue peptide
      that carries the putative ferroxidase site of E2 domain (FD1 peptide) has been
      claimed to encompass the same activity. We previously tested the ferroxidase
      activity of the synthetic FD1 peptide but we did not observe any activity above
      the background oxidation of Fe(II) by molecular oxygen. Here we used isothermal
      titration calorimetry to study Zn(II) and Fe(II) binding to the natural E2 domain
      of APP, and we employed the transferrin assay and oxygen consumption measurements
      to test the ferroxidase activity of the E2 domain. We found that this domain
      neither in the presence nor in the absence of the E1 domain binds Fe(II) and it
      is not able to catalyze the oxidation of Fe(II). Binding of Cu(II) to the E2
      domain did not induce ferroxidase activity contrary to the presence of redox
      active Cu(II) centers in ceruloplasmin or hephaestin. Thus, we conclude that E2
      or E1 domains of APP do not have ferroxidase activity and that the potential
      involvement of APP as a ferroxidase in the pathology of Alzheimer's disease must
      be re-evaluated. 

PMID- 23977246
TI  - Phase variation leads to the misidentification of a Neisseria gonorrhoeae
      virulence gene.
AB  - Neisseria gonorrhoeae is the causative agent of gonorrhea and an obligate
      pathogen of humans. The Opa proteins of these bacteria are known to mediate
      attachment and internalization by host cells, including neutrophils. The Opa
      protein repertoire of a typical N. gonorrhoeae isolate is encoded on ~11 genes
      distributed throughout the chromosome and is subject to stochastic changes in
      expression through phase variation. Together, these characteristics make Opa
      proteins a critical yet unpredictable aspect of any experimental investigation
      into the interaction of N. gonorrhoeae with host cells. The goal of this study
      was to identify novel virulence factors of N. gonorrhoeae by assessing the
      contribution of a set of uncharacterized hydrogen peroxide-induced genes to
      bacterial survival against neutrophil-mediated killing. To this end, a strain
      harboring an engineered mutation in the NGO0322 gene was identified that
      exhibited increased sensitivity to neutrophil-mediated killing, enhanced
      internalization by neutrophils, and the ability to induce high levels of
      neutrophil-generated reactive oxygen species. Each of these phenotypes reverted
      to near wild-type levels following genetic complementation of the NGO0322
      mutation. However, after immunoblot analysis of Opa proteins expressed by the
      isogenic parent, mutant, and genetically complemented strains, it was determined
      that phase variation had resulted in a disparity between the Opa profiles of
      these strains. To determine whether Opa phase variation, rather than NGO0322
      mutation, was the cause of the observed neutrophil-related phenotypes, NGO0322
      function was investigated in N. gonorrhoeae strains lacking all Opa proteins or
      constitutively expressing the OpaD variant. In both cases, mutation of NGO0322
      did not alter survival of gonococci in the presence of neutrophils. These results
      demonstrate the importance of controlling for the frequent and random variation
      in Opa protein production by N. gonorrhoeae when investigating host cell
      interactions.

PMID- 23977247
TI  - Epigenetic changes of lentiviral transgenes in porcine stem cells derived from
      embryonic origin.
AB  - Because of the physiological and immunological similarities that exist between
      pigs and humans, porcine pluripotent cell lines have been identified as important
      candidates for preliminary studies on human disease as well as a source for
      generating transgenic animals. Therefore, the establishment and characterization
      of porcine embryonic stem cells (pESCs), along with the generation of stable
      transgenic cell lines, is essential. In this study, we attempted to efficiently
      introduce transgenes into Epiblast stem cell (EpiSC)-like pESCs. Consequently, a
      pluripotent cell line could be derived from a porcine-hatched blastocyst.
      Enhanced green fluorescent protein (EGFP) was successfully introduced into the
      cells via lentiviral vectors under various multiplicities of infection, with
      pluripotency and differentiation potential unaffected after transfection.
      However, EGFP expression gradually declined during extended culture. This
      silencing effect was recovered by in vitro differentiation and treatment with 5
      azadeoxycytidine. This phenomenon was related to DNA methylation as determined by
      bisulfite sequencing. In conclusion, we were able to successfully derive EpiSC
      like pESCs and introduce transgenes into these cells using lentiviral vectors.
      This cell line could potentially be used as a donor cell source for transgenic
      pigs and may be a useful tool for studies involving EpiSC-like pESCs as well as
      aid in the understanding of the epigenetic regulation of transgenes. 

PMID- 23977249
TI  - Dietary plasticity of generalist and specialist ungulates in the Namibian Desert:
      a stable isotopes approach.
AB  - Desert ungulates live in adverse ecosystems that are particularly sensitive to
      degradation and global climate change. Here, we asked how two ungulate species
      with contrasting feeding habits, grazing gemsbok (Oryx g. gazella) and browsing
      springbok (Antidorcas marsupialis), respond to an increase in food availability
      during a pronounced rain period. We used a stable isotope approach to delineate
      the feeding habits of these two ungulates in the arid Kunene Region of Namibia.
      Our nineteen months field investigation included two time periods of drought when
      food availability for ungulates was lowest and an intermediate period with
      extreme, unusual rainfalls. We documented thirteen isotopically distinct food
      sources in the isotopic space of the study area. Our results indicated a
      relatively high dietary plasticity of gemsbok, which fed on a mixture of plants,
      including more than 30% of C3 plants during drought periods, but almost
      exclusively on C4 and CAM plant types when food was plentiful. During drought
      periods, the inferred gemsbok diets also consisted of up to 25% of Euphorbia
      damarana; an endemic CAM plant that is rich in toxic secondary plant compounds.
      In contrast, springbok were generalists, feeding on a higher proportion of C3
      than C4/CAM plants, irrespective of environmental conditions. Our results
      illustrate two dietary strategies in gemsbok and springbok which enable them to
      survive and coexist in the hostile Kunene arid ecosystem. 

PMID- 23977248
TI  - Comparing adjuvanted H28 and modified vaccinia virus ankara expressingH28 in a
      mouse and a non-human primate tuberculosis model.
AB  - Here we report for the first time on the immunogenicity and protective efficacy
      of a vaccine strategy involving the adjuvanted fusion protein "H28" (consisting
      of Ag85B-TB10.4-Rv2660c) and Modified Vaccinia Virus Ankara expressing H28. We
      show that a heterologous prime-boost regimen involving priming with H28 in a Th1
      adjuvant followed by boosting with H28 expressed by MVA (H28/MVA28) induced the
      highest percentage of IFN-gamma expressing T cells, the highest production of IFN
      gamma per single cell and the highest induction of CD8 T cells compared to either
      of the vaccines given alone. In contrast, in mice vaccinated with adjuvanted
      recombinant H28 alone (H28/H28) we observed the highest production of IL-2 per
      single cell and the highest frequency of antigen specific TNF-alpha/IL-2
      expressing CD4 T cells pre and post infection. Interestingly, TNF-alpha/IL-2
      expressing central memory-like CD4 T cells showed a significant positive
      correlation with protection at week 6 post infection, whereas the opposite was
      observed for post infection CD4 T cells producing only IFN-gamma. Moreover, as a
      BCG booster vaccine in a clinically relevant non-human primate TB model, the
      H28/H28 vaccine strategy induced a slightly more prominent reduction of clinical
      disease and pathology for up to one year post infection compared to H28/MVA28.
      Taken together, our data showed that the adjuvanted subunit and MVA strategies
      led to different T cell subset combinations pre and post infection and that TNF
      alpha/IL-2 double producing but not IFN-gamma single producing CD4 T cell subsets
      correlated with protection in the mouse TB model. Moreover, our data demonstrated
      that the H28 vaccine antigen was able to induce strong protection in both a mouse
      and a non-human primate TB model. 

PMID- 23977250
TI  - Prospective study of avian influenza virus infections among rural Thai villagers.
AB  - BACKGROUND: In 2008, 800 rural Thai adults living within Kamphaeng Phet Province
      were enrolled in a prospective cohort study of zoonotic influenza transmission.
      Serological analyses of enrollment sera suggested this cohort had experienced
      subclinical avian influenza virus (AIV) infections with H9N2 and H5N1 viruses.
      METHODS: After enrollment, participants were contacted weekly for 24 mos for
      acute influenza-like illnesses (ILI). Cohort members confirmed to have influenza
      A infections were enrolled with their household contacts in a family transmission
      study involving paired sera and respiratory swab collections. Cohort members also
      provided sera at 12 and 24 months after enrollment. Serologic and real-time RT
      PCR assays were performed against avian, swine, and human influenza viruses.
      RESULTS: Over the 2 yrs of follow-up, 81 ILI investigations in the cohort were
      conducted; 31 (38%) were identified as influenza A infections by qRT-PCR. Eighty
      three household contacts were enrolled; 12 (14%) reported ILIs, and 11 (92%) of
      those were identified as influenza infections. A number of subjects were found to
      have slightly elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2)
      virus: 21 subjects (2.7%) at 12-months and 40 subjects (5.1%) at 24-months. Among
      these, two largely asymptomatic acute infections with H9N2 virus were detected by
      >4-fold increases in annual serologic titers (final titers 1:80). While
      controlling for age and influenza vaccine receipt, moderate poultry exposure was
      significantly associated with elevated H9N2 titers (adjusted OR = 2.3; 95% CI,
      1.04-5.2) at the 24-month encounter. One subject had an elevated titer (1:20)
      against H5N1 during follow-up. CONCLUSIONS: From 2008-10, evidence for AIV
      infections was sparse among this rural population. Subclinical H9N2 AIV
      infections likely occurred, but serological results were confounded by antibody
      cross-reactions. There is a critical need for improved serological diagnostics to
      more accurately detect subclinical AIV infections in humans.

PMID- 23977251
TI  - Genetic variation in BCL2 3'-UTR was associated with lung cancer risk and
      prognosis in male Chinese population.
AB  - OBJECTIVES: Bcl-2 is a critical apoptosis inhibitor with established carcinogenic
      potential, and can confer cancer cell resistance to therapeutic treatments by
      activating anti-apoptotic cellular defense. We hypothesized that genetic variants
      of BCL2 gene may be associated with lung cancer susceptibility and prognosis.
      METHODS: Three selected tagSNPs of BCL2 (rs2279115, rs1801018, and rs1564483)
      were genotyped in 1017 paired male Chinese lung cancer cases and controls by
      TaqMan assay. The associations of these variants with risk of lung cancer and
      overall survival of 242 male advanced non-small-cell lung cancer (NSCLC) patients
      were separately investigated. RESULTS: Compared with the BCL2 3'UTR rs1564483GG
      genotype, the rs1564483GA, AA, and GA+AA genotypes were associated with
      significantly decreased susceptibilities of lung cancer in male Chinese (adjusted
      OR = 0.78, 0.73, and 0.76, P = 0.016, 0.038, and 0.007, respectively), while
      rs1564483A allele has a inverse dose-response relationship with lung cancer risk
      (P trend = 0.010). These effects were more evident in the elders, smokers, and
      subjects without family history of cancer (P trend = 0.017, 0.043 and 0.005,
      respectively). Furthermore, advanced NSCLC males carrying BCL2 rs1564483 GA+AA
      genotypes had significantly longer median survival time (Long-rank P = 0.036) and
      decreased death risk (adjusted HR = 0.69, P = 0.027) than patients with
      rs1564483GG genotype. These effects were more obvious in patients with smoking,
      stage IIIA, and in patients without surgery but underwent chemotherapy or
      radiotherapy (adjusted HR = 0.68, 0.49, 0.67, 0.69, 0.50, respectively, all
      P<0.05). CONCLUSION: The BCL2 3'UTR rs1564483A allele was associated with a
      decreased lung cancer risk and better survival for advanced NSCLC in male
      Chinese, which may offer a novel biomarker for identifying high-risk population
      and predicting clinical outcomes.

PMID- 23977252
TI  - Variation in carbon storage and its distribution by stand age and forest type in
      boreal and temperate forests in northeastern China.
AB  - The northeastern forest region of China is an important component of total
      temperate and boreal forests in the northern hemisphere. But how carbon (C) pool
      size and distribution varies among tree, understory, forest floor and soil
      components, and across stand ages remains unclear. To address this knowledge gap,
      we selected three major temperate and two major boreal forest types in
      northeastern (NE) China. Within both forest zones, we focused on four stand age
      classes (young, mid-aged, mature and over-mature). Results showed that total C
      storage was greater in temperate than in boreal forests, and greater in older
      than in younger stands. Tree biomass C was the main C component, and its
      contribution to the total forest C storage increased with increasing stand age.
      It ranged from 27.7% in young to 62.8% in over-mature stands in boreal forests
      and from 26.5% in young to 72.8% in over-mature stands in temperate forests.
      Results from both forest zones thus confirm the large biomass C storage capacity
      of old-growth forests. Tree biomass C was influenced by forest zone, stand age,
      and forest type. Soil C contribution to total forest C storage ranged from 62.5%
      in young to 30.1% in over-mature stands in boreal and from 70.1% in young to
      26.0% in over-mature in temperate forests. Thus soil C storage is a major C pool
      in forests of NE China. On the other hand, understory and forest floor C jointly
      contained less than 13% and <5%, in boreal and temperate forests respectively,
      and thus play a minor role in total forest C storage in NE China. 

PMID- 23977253
TI  - Anemia and risk factors in HAART naive and HAART experienced HIV positive persons
      in south west Ethiopia: a comparative study.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection and its treatment cause
      a range of hematological abnormalities. Anemia is one of the commonly observed
      hematologic manifestations in HIV positive persons and it has multifactorial
      origin. OBJECTIVE: We aimed to determine the prevalence and risk factors of
      anemia in highly active antiretroviral therapy (HAART) naive and HAART
      experienced HIV positive persons. METHODS: A facility-based comparative cross
      sectional study was conducted in Jimma University Specialized Hospital from
      February 1 to March 30, 2012. A total of 234 HIV positive persons, 117 HAART
      naive and 117 HAART experienced, were enrolled in this study. Blood and stool
      specimens were collected from each participant. Blood specimens were examined for
      complete blood count, CD4 count and blood film for malaria hemoparasite; whereas
      stool specimens were checked for ova of intestinal parasites. Socio-demographic
      characteristics and clinical data of the participants were collected using pre
      tested questionnaire. Statistical analysis of the data (Chi-square, student's t
      test, logistic regression) was done using SPSS V-16. RESULTS: The overall
      prevalence of anemia was 23.1%. The prevalence of anemia in HAART naive and HAART
      experienced persons was 29.9% and 16.2%, respectively (P = 0.014). Presence of
      opportunistic infections (P = 0.004, 95% CI = 1.69-15.46), CD4 count <200
      cells/ul (P = 0.001, 95% CI = 2.57-36.89) and rural residence (P = 0.03, 95% CI =
      1.12-10.39) were found to be predictors of anemia for HAART naive participants.
      On the other hand, HAART regimen (ZDV/3TC/NVP) (P = 0.019, 95% CI = 0.01-1.24)
      and the duration of HAART (P = 0.007, 95% CI = 0.003-0.40.24) were found to be
      predictors of anemia for HAART experienced groups. CONCLUSION: The prevalence of
      anemia in HAART naive persons was higher than HAART experienced persons. Risk
      factors for anemia in HAART naive and HAART experienced HIV positive persons were
      different. Hence, there is a need for longitudinal study to further explore the
      causes of HIV associated anemia and the pattern of hemoglobin changes with
      initiation of HAART.

PMID- 23977254
TI  - Plant SILAC: stable-isotope labelling with amino acids of arabidopsis seedlings
      for quantitative proteomics.
AB  - Stable Isotope Labelling by Amino acids in Cell culture (SILAC) is a powerful
      technique for comparative quantitative proteomics, which has recently been
      applied to a number of different eukaryotic organisms. Inefficient incorporation
      of labelled amino acids in cell cultures of Arabidopsis thaliana has led to very
      limited use of SILAC in plant systems. We present a method allowing, for the
      first time, efficient labelling with stable isotope-containing arginine and
      lysine of whole Arabidopsis seedlings. To illustrate the utility of this method,
      we have combined the high labelling efficiency (>95%) with quantitative
      proteomics analyses of seedlings exposed to increased salt concentration. In
      plants treated for 7 days with 80 mM NaCl, a relatively mild salt stress, 215
      proteins were identified whose expression levels changed significantly compared
      to untreated seedling controls. The 92 up-regulated proteins included proteins
      involved in abiotic stress responses and photosynthesis, while the 123 down
      regulated proteins were enriched in proteins involved in reduction of oxidative
      stress and other stress responses, respectively. Efficient labelling of whole
      Arabidopsis seedlings by this modified SILAC method opens new opportunities to
      exploit the genetic resources of Arabidopsis and analyse the impact of mutations
      on quantitative protein dynamics in vivo. 

PMID- 23977255
TI  - Elimination of von Hippel-Lindau function perturbs pancreas endocrine homeostasis
      in mice.
AB  - Mutations in the human homolog of the Vhlh gene [encoding the von-Hippel Lindau
      (VHL) protein] lead to tumor development. In mice, depletion of Vhlh in
      pancreatic beta-cells causes perturbed glucose homeostasis, but the role of this
      gene in other pancreatic cells is poorly understood. To investigate the function
      of VHL/HIF pathway in pancreatic cells, we inactivated Vhlh in the pancreatic
      epithelium as well as in the endocrine and exocrine lineages. Our results show
      that embryonic depletion of Vhlh within the pancreatic epithelium causes
      postnatal lethality due to severe hypoglycemia. The hypoglycemia is recapitulated
      in mice with endocrine-specific removal of Vhlh, while animals with loss of Vhlh
      predominantly in the exocrine compartment survive to adulthood with no overt
      defects in glucose metabolism. Mice with hypoglycemia display diminished insulin
      release in response to elevated glucose. Significantly, the glucagon response is
      impaired both in vivo (circulating glucagon levels) as well as in an in vitro
      secretion assay in isolated islets. Hypoxia also impairs glucagon secretion in a
      glucagon-expressing cell line in culture. Our results reveal a novel role for the
      hypoxia/HIF pathway in islet hormone secretion and maintenance of the fine
      balance that allows for the establishment of normoglycemia. 

PMID- 23977256
TI  - Calpain-2 compensation promotes angiotensin II-induced ascending and abdominal
      aortic aneurysms in calpain-1 deficient mice.
AB  - BACKGROUND AND OBJECTIVE: Recently, we demonstrated that angiotensin II (AngII)
      infusion profoundly increased both aortic protein and activity of calpains,
      calcium-activated cysteine proteases, in mice. In addition, pharmacological
      inhibition of calpain attenuated AngII-induced abdominal aortic aneurysm (AA) in
      mice. Recent studies have shown that AngII infusion into mice leads to aneurysmal
      formation localized to the ascending aorta. However, the precise functional
      contribution of calpain isoforms (-1 or -2) in AngII-induced abdominal AA
      formation is not known. Similarly, a functional role of calpain in AngII-induced
      ascending AA remains to be defined. Using BDA-410, an inhibitor of calpains, and
      calpain-1 genetic deficient mice, we examined the relative contribution of
      calpain isoforms in AngII-induced ascending and abdominal AA development.
      METHODOLOGY/RESULTS: To investigate the relative contribution of calpain-1 and -2
      in development of AngII-induced AAs, male LDLr -/- mice that were either calpain
      1 +/+ or -/- were fed a saturated fat-enriched diet and infused with AngII (1,000
      ng/kg/min) for 4 weeks. Calpain-1 deficiency had no significant effect on body
      weight or blood pressure during AngII infusion. Moreover, calpain-1 deficiency
      showed no discernible effects on AngII-induced ascending and abdominal AAs.
      Interestingly, AngII infusion induced increased expression of calpain-2 protein,
      thus compensating for total calpain activity in aortas of calpain-1 deficient
      mice. Oral administration of BDA-410, a calpain inhibitor, along with AngII
      infusion significantly attenuated AngII-induced ascending and abdominal AA
      formation in both calpain-1 +/+ and -/- mice as compared to vehicle administered
      mice. Furthermore, BDA-410 administration attenuated AngII-induced aortic medial
      hypertrophy and macrophage accumulation. Western blot and immunostaining analyses
      revealed BDA-410 administration attenuated AngII-induced C-terminal fragmentation
      of filamin A, an actin binding cytoskeletal protein in aorta. CONCLUSION: Calpain
      2 compensates for loss of calpain-1, and both calpain isoforms are involved in
      AngII-induced aortic aneurysm formation in mice.

PMID- 23977257
TI  - Impact of a manualized multifocal perinatal home-visiting program using
      psychologists on postnatal depression: the CAPEDP randomized controlled trial.
AB  - CONTEXT: Postnatal maternal depression (PND) is a significant risk factor for
      infant mental health. Although often targeted alongside other factors in
      perinatal home-visiting programs with vulnerable families, little impact on PND
      has been observed. OBJECTIVE: This study evaluates the impact on PND
      symptomatology of a multifocal perinatal home-visiting intervention using
      psychologists in a sample of women presenting risk factors associated with infant
      mental health difficulties. METHODS: 440 primiparous women were recruited at
      their seventh month of pregnancy. All were future first-time mothers, under 26,
      with at least one of three additional psychosocial risk factors: low educational
      level, low income, or planning to raise the child without the father. The
      intervention consisted of intensive multifocal home visits through to the child's
      second birthday. The control group received care as usual. PND symptomatology was
      assessed at baseline and three months after birth using the Edinburgh Postnatal
      Depression Scale (EPDS). RESULTS: At three months postpartum, mean (SD) EPDS
      scores were 9.4 (5.4) for the control group and 8.6 (5.4) for the intervention
      group (p = 0.18). The difference between the mean EPDS scores was 0.85 (95% CI:
      0.35; 1.34). The intervention group had significantly lower EPDS scores than
      controls in certain subgroups: women with few depressive symptoms at inclusion
      (EPDS <8): difference = 1.66 (95%CI: 0.17; 3.15), p = 0.05, adjusted for baseline
      EPDS score), women who were planning to raise the child with the child's father:
      difference = 1.45 (95%CI: 0.27; 2.62), p = 0.04 (adjusted); women with a higher
      educational level: difference = 1.59 (95%CI: 0.50; 2.68) p = 0.05 (adjusted).
      CONCLUSION: CAPEDP failed to demonstrate an overall impact on PND. However, post
      hoc analysis reveals the intervention was effective in terms of primary
      prevention and in subgroups of women without certain risk factors. Effective
      overall reduction of PND symptomatology for young, first-time mothers presenting
      additional psychosocial risk factors may require more tailored interventions.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT00392847 Promoting Parental Skills and
      Enhancing Attachment in Early Childhood (CAPEDP).

PMID- 23977258
TI  - Splicing factor transformer-2beta (Tra2beta) regulates the expression of
      regulator of G protein signaling 4 (RGS4) gene and is induced by morphine.
AB  - Regulator of G protein signaling 4 (RGS4) is a critical modulator of G protein
      coupled receptor (GPCR)-mediated signaling and plays important roles in many
      neural process and diseases. Particularly, drug-induced alteration in RGS4
      protein levels is associated with acute and chronic effects of drugs of abuse.
      However, the precise mechanism underlying the regulation of RGS4 expression is
      largely unknown. Here, we demonstrated that the expression of RGS4 gene was
      subject to regulation by alternative splicing of the exon 6. Transformer-2beta
      (Tra2beta), an important splicing factor, bound to RGS4 mRNA and increased the
      relative level of RGS4-1 mRNA isoform by enhancing the inclusion of exon 6.
      Meanwhile, Tra2beta increased the expression of full-length RGS4 protein. In rat
      brain, Tra2beta was co-localized with RGS4 in multiple opioid action-related
      brain regions. In addition, the acute and chronic morphine treatment induced
      alteration in the expression level of Tra2beta in rat locus coerulus (LC) in
      parallel to that of RGS4 proteins. It suggests that induction of this splicing
      factor may contribute to the change of RGS4 level elicited by morphine. Taken
      together, the results provide the evidence demonstrating the function of Tra2beta
      as a new mediator in opioid-induced signaling pathway via regulating RGS4
      expression. 

PMID- 23977259
TI  - Fibroblast growth factor receptor-2 expression in thyroid tumor progression:
      potential diagnostic application.
AB  - Fibroblast growth factor receptor-2 (FGFR-2) plays an important role in
      tumorigenesis. In thyroid cancer it has been observed a FGFR-2 down-modulation,
      but the role of this receptor has not been yet clarified. Therefore, we decided
      to examine the expression of both FGFR-2 isoform, FGFR-2-IIIb and FGFR-2-IIIc, in
      different histological thyroid variants such as hyperplasia, follicular adenoma
      and papillary carcinoma. Immunohistochemistry and quantitative Real-Time PCR
      analyses were performed on samples of hyperplasia, follicular adenoma and
      papillary carcinoma, compared with normal thyroid tissue. Thyroid hyperplasia did
      not show statistically significant reduction in FGFR-2 protein and mRNA levels.
      Interestingly, in both follicular adenoma and papillary carcinoma samples we
      observed a strongly reduced expression of both FGFR-2 isoforms. We speculate that
      FGFR-2 down-modulation might be an early event in thyroid carcinogenesis.
      Furthermore, we suggest the potential use of FGFR-2 as an early marker for
      thyroid cancer diagnosis. 

PMID- 23977260
TI  - A large animal model for CNGB1 autosomal recessive retinitis pigmentosa.
AB  - Retinal dystrophies in dogs are invaluable models of human disease. Progressive
      retinal atrophy (PRA) is the canine equivalent of retinitis pigmentosa (RP).
      Similar to RP, PRA is a genetically heterogenous condition. We investigated PRA
      in the Papillon breed of dog using homozygosity mapping and haplotype
      construction of single nucleotide polymorphisms within a small family group to
      identify potential positional candidate genes. Based on the phenotypic
      similarities between the PRA-affected Papillons, mouse models and human patients,
      CNGB1 was selected as the most promising positional candidate gene. CNGB1 was
      sequenced and a complex mutation consisting of the combination of a one basepair
      deletion and a 6 basepair insertion was identified in exon 26
      (c.2387delA;2389_2390insAGCTAC) leading to a frameshift and premature stop codon.
      Immunohistochemistry (IHC) of pre-degenerate retinal sections from a young
      affected dog showed absence of labeling using a C-terminal CNGB1 antibody.
      Whereas an antibody directed against the N-terminus of the protein, which also
      recognizes the glutamic acid rich proteins arising from alternative splicing of
      the CNGB1 transcript (upstream of the premature stop codon), labeled rod outer
      segments. CNGB1 combines with CNGA1 to form the rod cyclic nucleotide gated
      channel and previous studies have shown the requirement of CNGB1 for normal
      targeting of CNGA1 to the rod outer segment. In keeping with these previous
      observations, IHC showed a lack of detectable CNGA1 protein in the rod outer
      segments of the affected dog. A population study did not identify the CNGB1
      mutation in PRA-affected dogs in other breeds and documented that the CNGB1
      mutation accounts for ~70% of cases of Papillon PRA in our PRA-affected canine
      DNA bank. CNGB1 mutations are one cause of autosomal recessive RP making the
      CNGB1 mutant dog a valuable large animal model of the condition.

PMID- 23977263
TI  - The symmetry of children's knees is linked to their adult sprinting speed and
      their willingness to sprint in a long-term Jamaican study.
AB  - Jamaican athletes are prominent in sprint running but the reasons for their
      success are not clear. Here we consider the possibility that symmetry,
      particularly symmetry of the legs, in Jamaican children is linked to high
      sprinting speed in adults. Our study population was a cohort of 288 rural
      children, mean age 8.2 (+/- 1 SD = 1.7) years in 1996. Symmetry was measured in
      1996 and 2006 from the fluctuating asymmetry (FA) of three lower-body traits and
      we constructed a lower body composite FA trait (Comp lb-FA). In 2010 we measured
      sprinting speed (for 90 m and 180 m races) in participants recruited from our
      original cohort. There were 163 untrained adults in our sample. We found: (i)
      high Comp lb and knee symmetry in 1996 and 2006 were linked to fast sprinting
      times in our 2010 runners and (ii) our sample of sprinters appears to have self
      selected for greater symmetry. We conclude that high knee symmetry in childhood
      is linked to an ability to sprint fast in adult Jamaicans as well as a readiness
      to sprint.

PMID- 23977262
TI  - A tumor-penetrating peptide modification enhances the antitumor activity of
      thymosin alpha 1.
AB  - A serious limitation of numerous antitumor drugs is the incapacity to penetrate
      solid tumors. However, addition of an RGD fragment to peptide drugs might solve
      this problem. In this study, we explored whether the introduction of a
      permeability-enhancing sequence, such as iRGD (CRGDK/RGPD/EC) fragments, would
      enhance the activity of thymosin alpha 1 (Talpha1). The modified Talpha1 (Talpha1
      iRGD) was successfully expressed and purified, and the in vitro assay showed that
      Talpha1-iRGD presented a similar activity as Talpha1 in promoting proliferation
      of mouse splenocytes. Meanwhile, cell adhesion analysis revealed that Talpha1
      iRGD exhibited more specific and greater binding with tumor cells compared with
      Talpha1. Furthermore, the iRGD fragment evidently enhanced the basal ability of
      Talpha1 to inhibit proliferation of cancer cells in vitro, particularly of mouse
      melanoma cell line B16F10 and human lung cancer cell line H460. Our findings
      indicated that the addition of an iRGD fragment increased the anti-proliferative
      activity of Talpha1 against cancer cells by improving the ability of Talpha1 to
      penetrate the tumor cells. This study highlighted the important roles of an iRGD
      sequence in the therapeutic strategy of Talpha1-iRGD. Thus, Talpha1-iRGD could be
      a novel drug candidate for cancer treatment. 

PMID- 23977261
TI  - Effect of doxorubicin/pluronic SP1049C on tumorigenicity, aggressiveness, DNA
      methylation and stem cell markers in murine leukemia.
AB  - PURPOSE: Pluronic block copolymers are potent sensitizers of multidrug resistant
      cancers. SP1049C, a Pluronic-based micellar formulation of doxorubicin (Dox) has
      completed Phase II clinical trial and demonstrated safety and efficacy in
      patients with advanced adenocarcinoma of the esophagus and gastroesophageal
      junction. This study elucidates the ability of SP1049C to deplete cancer stem
      cells (CSC) and decrease tumorigenicity of cancer cells in vivo. EXPERIMENTAL
      DESIGN: P388 murine leukemia ascitic tumor was grown in BDF1 mice. The animals
      were treated with: (a) saline, (b) Pluronics alone, (c) Dox or (d) SP1049C. The
      ascitic cancer cells were isolated at different passages and examined for 1) in
      vitro colony formation potential, 2) in vivo tumorigenicity and aggressiveness,
      3) development of drug resistance and Wnt signaling activation 4) global DNA
      methylation profiles, and 5) expression of CSC markers. RESULTS: SP1049C
      treatment reduced tumor aggressiveness, in vivo tumor formation frequency and in
      vitro clonogenic potential of the ascitic cells compared to drug, saline and
      polymer controls. SP1049C also prevented overexpression of BCRP and activation of
      Wnt-beta-catenin signaling observed with Dox alone. Moreover, SP1049C
      significantly altered the DNA methylation profiles of the cells. Finally, SP1049C
      decreased CD133(+) P388 cells populations, which displayed CSC-like properties
      and were more tumorigenic compared to CD133(-) cells. CONCLUSIONS: SP1049C
      therapy effectively suppresses the tumorigenicity and aggressiveness of P388
      cells in a mouse model. This may be due to enhanced activity of SP1049C against
      CSC and/or altered epigenetic regulation restricting appearance of malignant
      cancer cell phenotype.

PMID- 23977264
TI  - Pyridoxine for prevention of hand-foot syndrome caused by chemotherapy: a
      systematic review.
AB  - BACKGROUND: Hand-foot syndrome (HFS) is a relatively frequent dermatologic toxic
      reaction to certain anti-cancer chemotherapies. The syndrome can evolve into a
      distressing condition that limits function and affects quality of life.
      Pyridoxine (vitamin B6) has been used empirically for the prevention of HFS
      caused by anti-cancer therapy. However, evidence of its efficacy remains
      controversial. METHODOLOGY//PRINCIPAL FINDINGS: Systematic literature searches
      were conducted on the Cochrane Library, PUBMED, EMBASE, LILACS, CBM, CNKI, VIP,
      WANFANG and the U.S. ClinicalTrials.gov website. We included all related
      randomized controlled trials (RCTs) irrespective of language. Reviewers from
      different professions independently assessed all potential studies and extracted
      data. Subgroup analysis was planned according to dose of pyridoxine. 5 RCTs
      involving 607 patients were contributed to the meta-analysis. No significant
      differences were found between patients receiving pyridoxine and placebo for
      prevention of incidence of HFS and grade 2 or worse HFS (relative risk (RR) 0.96,
      95%confidence interval (CI) 0.86-1.06; RR0.95, 95%CI 0.73-1.24, respectively).
      Similarly, no significant improvement in quality of life was detected among
      patients. However, significant difference was found for prevention of grade 2 or
      worse HFS with pyridoxine 400 mg daily compared to 200 mg (RR0.55, 95%CI 0.33
      0.92). CONCLUSIONS/SIGNIFICANCE: There is inadequate evidence to make any
      recommendation about using pyridoxine for prevention of HFS caused by
      chemotherapy. However, pyridoxine 400 mg may have some efficacy. Further studies
      of large sample sizes are needed to evaluate the efficacy and safety of
      pyridoxine, especially at high dose, in comparison with placebo.

PMID- 23977265
TI  - Predictive value of XPD polymorphisms on platinum-based chemotherapy in non-small
      cell lung cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: The correlation between xeroderma pigmentosum group D (XPD)
      polymorphisms (Lys751Gln and Asp312Asn) and clinical outcomes of non-small cell
      lung cancer (NSCLC) patients, who received platinum-based chemotherapy (Pt
      chemotherapy), is still inconclusive. This meta-analysis was aimed to
      systematically review published evidence and ascertain the exact role of XPD
      polymorphisms. METHODS: Databases of MEDLINE and EMBASE were searched up to April
      2013 to identify eligible studies. A rigorous quality assessment of eligible
      studies was conducted according the Newcastle-Ottawa Quality Assessment Scales.
      The relationship between XPD polymorphisms and response to Pt-chemotherapy and
      survival was analyzed. RESULTS: A total of 22 eligible studies were included and
      analyzed in this meta-analysis. The overall analysis suggested that the XPD
      Lys751Gln polymorphism was not associated with response to Pt-chemotherapy or
      survival. However, the XPD 312Asn allele was significantly associated with poor
      response to Pt-chemotherapy compared with the Asp312 allele (Asn vs. Asp: OR =
      0.435, 95% CI: 0.261-0.726). Additionally, the variant genotype of XPD Asp312Asn
      polymorphism was associated with favorable survival in Caucasian (AspAsn vs.
      AspAsp: HR = 0.781, 95% CI: 0.619-0.986) but unfavorable survival in Asian
      (AspAsn+AsnAsn vs. AspAsp: HR = 1.550, 95% CI: 1.038-2.315). CONCLUSIONS: These
      results suggest that XPD Asp312Asn polymorphism may function as a predictive
      biomarker on platinum-based chemotherapy in NSCLC and further studies are
      warranted.

PMID- 23977266
TI  - Flt3 does not play a critical role in murine myeloid leukemias induced by MLL
      fusion genes.
AB  - Leukemias harboring MLL translocations are frequent in children and adults, and
      respond poorly to therapies. The receptor tyrosine kinase FLT3 is highly
      expressed in these leukemias. In vitro studies have shown that pediatric MLL
      rearranged ALL cells are sensitive to FLT3 inhibitors and clinical trials are
      ongoing to measure their therapeutic efficacy. We sought to determine the
      contribution of Flt3 in the pathogenesis of MLL-rearranged leukemias using a
      myeloid leukemia mouse model. Bone marrow from Flt3 null mice transduced with MLL
      ENL or MLL-CBP was transplanted into host mice and Flt3 (-/-) leukemias were
      compared to their Flt3 wild type counterparts. Flt3 deficiency did not delay
      disease onset and had minimal impact on leukemia characteristics. To determine
      the anti-leukemic effect of FLT3 inhibition we studied the sensitivity of MLL-ENL
      leukemia cells to the FLT3 inhibitor PKC412 ex vivo. As previously reported for
      human MLL-rearranged leukemias, murine MLL-ENL leukemia cells with higher Flt3
      levels were more sensitive to the cytotoxicity of PKC412. Interestingly, Flt3
      deficient leukemia samples also displayed some sensitivity to PKC412. Our
      findings demonstrate that myeloid leukemias induced by MLL-rearranged genes are
      not dependent upon Flt3 signaling. They also highlight the discrepancy between
      the sensitivity of cells to Flt3 inhibition in vitro and the lack of contribution
      of Flt3 to the pathogenesis of MLL-rearranged leukemias in vivo. 

PMID- 23977267
TI  - Novel application of confocal laser scanning microscopy and 3D volume rendering
      toward improving the resolution of the fossil record of charcoal.
AB  - Variations in the abundance of fossil charcoals between rocks and sediments are
      assumed to reflect changes in fire activity in Earth's past. These variations in
      fire activity are often considered to be in response to environmental, ecological
      or climatic changes. The role that fire plays in feedbacks to such changes is
      becoming increasingly important to understand and highlights the need to create
      robust estimates of variations in fossil charcoal abundance. The majority of
      charcoal based fire reconstructions quantify the abundance of charcoal particles
      and do not consider the changes in the morphology of the individual particles
      that may have occurred due to fragmentation as part of their transport history.
      We have developed a novel application of confocal laser scanning microscopy
      coupled to image processing that enables the 3-dimensional reconstruction of
      individual charcoal particles. This method is able to measure the volume of both
      microfossil and mesofossil charcoal particles and allows the abundance of
      charcoal in a sample to be expressed as total volume of charcoal. The method
      further measures particle surface area and shape allowing both relationships
      between different size and shape metrics to be analysed and full consideration of
      variations in particle size and size sorting between different samples to be
      studied. We believe application of this new imaging approach could allow
      significant improvement in our ability to estimate variations in past fire
      activity using fossil charcoals. 

PMID- 23977268
TI  - Neural substrates for judgment of self-agency in ambiguous situations.
AB  - The sense of agency is the attribution of oneself as the cause of one's own
      actions and their effects. Accurate agency judgments are essential for adaptive
      behaviors in dynamic environments, especially in conditions of uncertainty.
      However, it is unclear how agency judgments are made in ambiguous situations
      where self-agency and non-self-agency are both possible. Agency attribution is
      thus thought to require higher-order neurocognitive processes that integrate
      several possibilities. Furthermore, neural activity specific to self-attribution,
      as compared with non-self-attribution, may reflect higher-order critical
      operations that contribute to constructions of self-consciousness. Based on these
      assumptions, the present study focused on agency judgments under ambiguous
      conditions and examined the neural correlates of this operation with functional
      magnetic resonance imaging. Participants performed a simple but demanding agency
      judgment task, which required them to report on whether they attributed their own
      action as the cause of a visual stimulus change. The temporal discrepancy between
      the participant's action and the visual events was adaptively set to be maximally
      ambiguous for each individual on a trial-by-trial basis. Comparison with results
      for a control condition revealed that the judgment of agency was associated with
      activity in lateral temporo-parietal areas, medial frontal areas, the
      dorsolateral prefrontal area, and frontal operculum/insula regions. However, most
      of these areas did not differentiate between self- and non-self-attribution.
      Instead, self-attribution was associated with activity in posterior midline
      areas, including the precuneus and posterior cingulate cortex. These results
      suggest that deliberate self-attribution of an external event is principally
      associated with activity in posterior midline structures, which is imperative for
      self-consciousness. 

PMID- 23977269
TI  - Akita spontaneously type 1 diabetic mice exhibit elevated vascular arginase and
      impaired vascular endothelial and nitrergic function.
AB  - BACKGROUND: Elevated arginase (Arg) activity is reported to be involved in
      diabetes-induced vascular endothelial dysfunction. It can reduce L-arginine
      availability to nitric oxide (NO) synthase (NOS) and NO production. Akita mice, a
      genetic non-obese type 1 diabetes model, recapitulate human diabetes. We
      determined the role of Arg in a time-course of diabetes-associated endothelial
      dysfunction in aorta and corpora cavernosa (CC) from Akita mice. METHODS AND
      RESULTS: Endothelium-dependent relaxation, Arg and NOS activity, and protein
      expression levels of Arg and constitutive NOS were assessed in aortas and CC from
      Akita and non-diabetic wild type (WT) mice at 4, 12 and 24 wks of age. Systolic
      blood pressure (SBP) was assessed by tail cuff. In aorta and CC, Akita mice
      exhibited a progressive impairment of vascular endothelial and nitrergic function
      increased Arg activity and expression (Arg1 in aorta and both Arg1 and Arg2 in
      CC) compared with that of age-matched WT mice. Treatment of aorta and CC from
      Akita mice with an Arg inhibitor (BEC or ABH) reduced diabetes-induced elevation
      of Arg activity and restored endothelial and nitrergic function. Reduced levels
      of phospho-eNOS at Ser(1177) (in aorta and CC) and nNOS expression (in CC) were
      observed in Akita mice at 12 and 24 wks. Akita mice also had decreased NOS
      activity in aorta and CC at 12 and 24 wks that was restored by BEC treatment.
      Further, Akita mice exhibited moderately increased SBP at 24 wks and increased
      sensitivity to PE-induced contractions in aorta and sympathetic nerve stimulation
      in CC at 12 and 24 wks. CONCLUSIONS: Over 24 wks of diabetes in Akita mice, both
      aortic and cavernosal tissues exhibited increased Arg activity/expression,
      contributing to impaired endothelial and nitrergic function and reduced NO
      production. Our findings demonstrate involvement of Arg activity in diabetes
      induced impairment of vascular function in Akita mouse.

PMID- 23977270
TI  - Human glioblastoma multiforme: p53 reactivation by a novel MDM2 inhibitor.
AB  - Cancer development and chemo-resistance are often due to impaired functioning of
      the p53 tumor suppressor through genetic mutation or sequestration by other
      proteins. In glioblastoma multiforme (GBM), p53 availability is frequently
      reduced because it binds to the Murine Double Minute-2 (MDM2) oncoprotein, which
      accumulates at high concentrations in tumor cells. The use of MDM2 inhibitors
      that interfere with the binding of p53 and MDM2 has become a valid approach to
      inhibit cell growth in a number of cancers; however little is known about the
      efficacy of these inhibitors in GBM. We report that a new small-molecule
      inhibitor of MDM2 with a spirooxoindolepyrrolidine core structure, named ISA27,
      effectively reactivated p53 function and inhibited human GBM cell growth in vitro
      by inducing cell cycle arrest and apoptosis. In immunoincompetent BALB/c nude
      mice bearing a human GBM xenograft, the administration of ISA27 in vivo activated
      p53, inhibited cell proliferation and induced apoptosis in tumor tissue.
      Significantly, ISA27 was non-toxic in an in vitro normal human cell model and an
      in vivo mouse model. ISA27 administration in combination with temozolomide (TMZ)
      produced a synergistic inhibitory effect on GBM cell viability in vitro,
      suggesting the possibility of lowering the dose of TMZ used in the treatment of
      GBM. In conclusion, our data show that ISA27 releases the powerful antitumor
      capacities of p53 in GBM cells. The use of this MDM2 inhibitor could become a
      novel therapy for the treatment of GBM patients. 

PMID- 23977271
TI  - Retinal ganglion cell dendritic atrophy in DBA/2J glaucoma.
AB  - Glaucoma is a complex disease affecting an estimated 70 million people worldwide,
      characterised by the progressive degeneration of retinal ganglion cells and
      accompanying visual field loss. The common site of damage to retinal ganglion
      cells is thought to be at the optic nerve head, however evidence from other optic
      neuropathies and neurodegenerative disorders suggests that dendritic structures
      undergo a prolonged period of atrophy that may accompany or even precede soma
      loss and neuronal cell death. Using the DBA/2J mouse model of glaucoma this
      investigation aims to elucidate the impact of increasing intraocular pressure on
      retinal ganglion cell dendrites using DBA/2J mice that express YFP throughout the
      retinal ganglion cells driven by Thy1 (DBA/2J.Thy1(YFP)) and DiOlistically
      labelled retinal ganglion cells in DBA/2J mice. Here we show retinal ganglion
      cell dendritic degeneration in DiOlistically labelled DBA/2J retinal ganglion
      cells but not in the DBA/2J.Thy1(YFP) retinal ganglion cells suggesting that a
      potential downregulation of Thy1 allows only 'healthy' retinal ganglion cells to
      express YFP. These data may highlight alternative pathways to retinal ganglion
      cell loss in DBA/2J glaucoma. 

PMID- 23977272
TI  - Polo-like kinase 1 inhibits the activity of positive transcription elongation
      factor of RNA Pol II b (P-TEFb).
AB  - Polo-like kinase 1 (Plk1) is a highly conserved Ser/Thr kinase in eukaryotes and
      plays a critical role in various aspects of the cell cycle. Plk1 exerts its
      multiple functions by phosphorylating its substrates. In this study, we found
      that Plk1 can interact with cyclin T1/Cdk9 complex-the main form of the positive
      transcription elongation complex b (P-TEFb), and its C-terminal polo-box domain
      is responsible for the binding. Further analysis indicated that Plk1 could
      phosphorylate cyclin T1 at Ser564 and inhibit the kinase activity of cyclin
      T1/Cdk9 complex on phosphorylation of the C-terminal domain (CTD) of RNA
      polymerase II. By taking the approach of luciferase assay, we demonstrated that
      over-expression of both wild type Plk1 and constitutively active form of Plk1
      inhibits the P-TEFb dependent HIV-1 LTR transcription, while knockdown of Plk1
      increases the HIV-1 LTR transcription. Consistently, the data from the HIV-1
      pseudovirus reporter assay indicated that Plk1 blocks the gene expression of HIV
      1 pseudovirus. Taken together, our results revealed that Plk1 negatively
      regulates the RNA polymerase II-dependent transcription through inhibiting the
      activity of cyclin T1/Cdk9 complex. 

PMID- 23977273
TI  - Environmental consequences of invasive species: greenhouse gas emissions of
      insecticide use and the role of biological control in reducing emissions.
AB  - Greenhouse gas emissions associated with pesticide applications against invasive
      species constitute an environmental cost of species invasions that has remained
      largely unrecognized. Here we calculate greenhouse gas emissions associated with
      the invasion of an agricultural pest from Asia to North America. The soybean
      aphid, Aphis glycines, was first discovered in North America in 2000, and has led
      to a substantial increase in insecticide use in soybeans. We estimate that the
      manufacture, transport, and application of insecticides against soybean aphid
      results in approximately 10.6 kg of carbon dioxide (CO2) equivalent greenhouse
      gasses being emitted per hectare of soybeans treated. Given the acreage sprayed,
      this has led to annual emissions of between 6 and 40 million kg of CO2 equivalent
      greenhouse gasses in the United States since the invasion of soybean aphid,
      depending on pest population size. Emissions would be higher were it not for the
      development of a threshold aphid density below which farmers are advised not to
      spray. Without a threshold, farmers tend to spray preemptively and the threshold
      allows farmers to take advantage of naturally occurring biological control of the
      soybean aphid, which can be substantial. We find that adoption of the soybean
      aphid economic threshold can lead to emission reductions of approximately 300
      million kg of CO2 equivalent greenhouse gases per year in the United States.
      Previous studies have documented that biological control agents such as lady
      beetles are capable of suppressing aphid densities below this threshold in over
      half of the soybean acreage in the U.S. Given the acreages involved this suggests
      that biological control results in annual emission reductions of over 200 million
      kg of CO2 equivalents. These analyses show how interactions between invasive
      species and organisms that suppress them can interact to affect greenhouse gas
      emissions. 

PMID- 23977275
TI  - Quantifying plant colour and colour difference as perceived by humans using
      digital images.
AB  - Human perception of plant leaf and flower colour can influence species
      management. Colour and colour contrast may influence the detectability of
      invasive or rare species during surveys. Quantitative, repeatable measures of
      plant colour are required for comparison across studies and generalisation across
      species. We present a standard method for measuring plant leaf and flower colour
      traits using images taken with digital cameras. We demonstrate the method by
      quantifying the colour of and colour difference between the flowers of eleven
      grassland species near Falls Creek, Australia, as part of an invasive species
      detection experiment. The reliability of the method was tested by measuring the
      leaf colour of five residential garden shrub species in Ballarat, Australia using
      five different types of digital camera. Flowers and leaves had overlapping but
      distinct colour distributions. Calculated colour differences corresponded well
      with qualitative comparisons. Estimates of proportional cover of yellow flowers
      identified using colour measurements correlated well with estimates obtained by
      measuring and counting individual flowers. Digital SLR and mirrorless cameras
      were superior to phone cameras and point-and-shoot cameras for producing reliable
      measurements, particularly under variable lighting conditions. The analysis of
      digital images taken with digital cameras is a practicable method for quantifying
      plant flower and leaf colour in the field or lab. Quantitative, repeatable
      measurements allow for comparisons between species and generalisations across
      species and studies. This allows plant colour to be related to human perception
      and preferences and, ultimately, species management. 

PMID- 23977274
TI  - Multimodal MRI and (31)P-MRS investigations of the ACTA1(Asp286Gly) mouse model
      of nemaline myopathy provide evidence of impaired in vivo muscle function,
      altered muscle structure and disturbed energy metabolism.
AB  - Nemaline myopathy (NM), the most common non-dystrophic congenital disease of
      skeletal muscle, can be caused by mutations in the skeletal muscle alpha-actin
      gene (ACTA1) (~25% of all NM cases and up to 50% of severe forms of NM). Muscle
      function of the recently generated transgenic mouse model carrying the human
      Asp286Gly mutation in the ACTA1 gene (Tg(ACTA1)(Asp286Gly)) has been mainly
      investigated in vitro. Therefore, we aimed at providing a comprehensive picture
      of the in vivo hindlimb muscle function of Tg(ACTA1)(Asp286Gly) mice by combining
      strictly noninvasive investigations. Skeletal muscle anatomy (hindlimb muscles,
      intramuscular fat volumes) and microstructure were studied using multimodal
      magnetic resonance imaging (Dixon, T2, Diffusion Tensor Imaging [DTI]). Energy
      metabolism was studied using 31-phosphorus Magnetic Resonance Spectroscopy ((31)P
      MRS). Skeletal muscle contractile performance was investigated while applying a
      force-frequency protocol (1-150 Hz) and a fatigue protocol (6 min-1.7 Hz).
      Tg(ACTA1)(Asp286Gly) mice showed a mild muscle weakness as illustrated by the
      reduction of both absolute (30%) and specific (15%) maximal force production.
      Dixon MRI did not show discernable fatty infiltration in Tg(ACTA1)(Asp286Gly)
      mice indicating that this mouse model does not reproduce human MRI findings.
      Increased T2 values were observed in Tg(ACTA1)(Asp286Gly) mice and might reflect
      the occurrence of muscle degeneration/regeneration process. Interestingly, T2
      values were linearly related to muscle weakness. DTI experiments indicated lower
      lambda2 and lambda3 values in Tg(ACTA1)(Asp286Gly) mice, which might be
      associated to muscle atrophy and/or the presence of histological anomalies.
      Finally (31)P-MRS investigations illustrated an increased anaerobic energy cost
      of contraction in Tg(ACTA1)(Asp286Gly) mice, which might be ascribed to
      contractile and non-contractile processes. Overall, we provide a unique set of
      information about the anatomic, metabolic and functional consequences of the
      Asp286Gly mutation that might be considered as relevant biomarkers for monitoring
      the severity and/or the progression of NM and for assessing the efficacy of
      potential therapeutic interventions. 

PMID- 23977277
TI  - Modulation of ocular surface glycocalyx barrier function by a galectin-3 N
      terminal deletion mutant and membrane-anchored synthetic glycopolymers.
AB  - BACKGROUND: Interaction of transmembrane mucins with the multivalent carbohydrate
      binding protein galectin-3 is critical to maintaining the integrity of the ocular
      surface epithelial glycocalyx. This study aimed to determine whether disruption
      of galectin-3 multimerization and insertion of synthetic glycopolymers in the
      plasma membrane could be used to modulate glycocalyx barrier function in corneal
      epithelial cells. METHODOLOGY/PRINCIPAL FINDINGS: Abrogation of galectin-3
      biosynthesis in multilayered cultures of human corneal epithelial cells using
      siRNA, and in galectin-3 null mice, resulted in significant loss of corneal
      barrier function, as indicated by increased permeability to the rose bengal
      diagnostic dye. Addition of beta-lactose, a competitive carbohydrate inhibitor of
      galectin-3 binding activity, to the cell culture system, transiently disrupted
      barrier function. In these experiments, treatment with a dominant negative
      inhibitor of galectin-3 polymerization lacking the N-terminal domain, but not
      full-length galectin-3, prevented the recovery of barrier function to basal
      levels. As determined by fluorescence microscopy, both cellobiose- and lactose
      containing glycopolymers incorporated into apical membranes of corneal epithelial
      cells, independently of the chain length distribution of the densely
      glycosylated, polymeric backbones. Membrane incorporation of cellobiose
      glycopolymers impaired barrier function in corneal epithelial cells, contrary to
      their lactose-containing counterparts, which bound to galectin-3 in pull-down
      assays. CONCLUSIONS/SIGNIFICANCE: These results indicate that galectin-3
      multimerization and surface recognition of lactosyl residues is required to
      maintain glycocalyx barrier function at the ocular surface. Transient
      modification of galectin-3 binding could be therapeutically used to enhance the
      efficiency of topical drug delivery.

PMID- 23977276
TI  - Efficacy and safety of a liposome-based vaccine against protein Tau, assessed in
      tau.P301L mice that model tauopathy.
AB  - Progressive aggregation of protein Tau into oligomers and fibrils correlates with
      cognitive decline and synaptic dysfunction, leading to neurodegeneration in
      vulnerable brain regions in Alzheimer's disease. The unmet need of effective
      therapy for Alzheimer's disease, combined with problematic pharmacological
      approaches, led the field to explore immunotherapy, first against amyloid
      peptides and recently against protein Tau. Here we adapted the liposome-based
      amyloid vaccine that proved safe and efficacious, and incorporated a synthetic
      phosphorylated peptide to mimic the important phospho-epitope of protein Tau at
      residues pS396/pS404. We demonstrate that the liposome-based vaccine elicited,
      rapidly and robustly, specific antisera in wild-type mice and in Tau.P301L mice.
      Long-term vaccination proved to be safe, because it improved the clinical
      condition and reduced indices of tauopathy in the brain of the Tau.P301L mice,
      while no signs of neuro-inflammation or other adverse neurological effects were
      observed. The data corroborate the hypothesis that liposomes carrying
      phosphorylated peptides of protein Tau have considerable potential as safe and
      effective treatment against tauopathies, including Alzheimer's disease. 

PMID- 23977278
TI  - Transcriptome analysis of chlorantraniliprole resistance development in the
      diamondback moth Plutella xylostella.
AB  - BACKGROUND: The diamondback moth Plutella xyllostella has developed a high level
      of resistance to the latest insecticide chlorantraniliprole. A better
      understanding of P. xylostella's resistance mechanism to chlorantraniliprole is
      needed to develop effective approaches for insecticide resistance management.
      PRINCIPAL FINDINGS: To provide a comprehensive insight into the resistance
      mechanisms of P. xylostella to chlorantraniliprole, transcriptome assembly and
      tag-based digital gene expression (DGE) system were performed using Illumina
      HiSeqTM 2000. The transcriptome analysis of the susceptible strain (SS) provided
      45,231 unigenes (with the size ranging from 200 bp to 13,799 bp), which would be
      efficient for analyzing the differences in different chlorantraniliprole
      resistant P. xylostella stains. DGE analysis indicated that a total of 1215 genes
      (189 up-regulated and 1026 down-regulated) were gradient differentially expressed
      among the susceptible strain (SS) and different chlorantraniliprole-resistant P.
      xylostella strains, including low-level resistance (GXA), moderate resistance
      (LZA) and high resistance strains (HZA). A detailed analysis of gradient
      differentially expressed genes elucidated the existence of a phase-dependent
      divergence of biological investment at the molecular level. The genes related to
      insecticide resistance, such as P450, GST, the ryanodine receptor, and connectin,
      had different expression profiles in the different chlorantraniliprole-resistant
      DGE libraries, suggesting that the genes related to insecticide resistance are
      involved in P. xylostella resistance development against chlorantraniliprole. To
      confirm the results from the DGE, the expressional profiles of 4 genes related to
      insecticide resistance were further validated by qRT-PCR analysis. CONCLUSIONS:
      The obtained transcriptome information provides large gene resources available
      for further studying the resistance development of P. xylostella to pesticides.
      The DGE data provide comprehensive insights into the gene expression profiles of
      the different chlorantraniliprole-resistant stains. These genes are specifically
      related to insecticide resistance, with different expressional profiles
      facilitating the study of the role of each gene in chlorantraniliprole resistance
      development.

PMID- 23977279
TI  - Genotypes and pathogenicity of cellulitis isolates reveal traits that modulate
      APEC virulence.
AB  - We characterized 144 Escherichia coli isolates from severe cellulitis lesions in
      broiler chickens from South Brazil. Analysis of susceptibility to 15
      antimicrobials revealed frequencies of resistance of less than 30% for most
      antimicrobials except tetracycline (70%) and sulphonamides (60%). The genotyping
      of 34 virulence-associated genes revealed that all the isolates harbored
      virulence factors related to adhesion, iron acquisition and serum resistance,
      which are characteristic of the avian pathogenic E. coli (APEC) pathotype. ColV
      plasmid-associated genes (cvi/cva, iroN, iss, iucD, sitD, traT, tsh) were
      especially frequent among the isolates (from 66.6% to 89.6%). According to the
      Clermont method of ECOR phylogenetic typing, isolates belonged to group D
      (47.2%), to group A (27.8%), to group B2 (17.4%) and to group B1 (7.6%); the
      group B2 isolates contained the highest number of virulence-associated genes.
      Clonal relationship analysis using the ARDRA method revealed a similarity level
      of 57% or higher among isolates, but no endemic clone. The virulence of the
      isolates was confirmed in vivo in one-day-old chicks. Most isolates (72.9%)
      killed all infected chicks within 7 days, and 65 isolates (38.1%) killed most of
      them within 24 hours. In order to analyze differences in virulence among the APEC
      isolates, we created a pathogenicity score by combining the times of death with
      the clinical symptoms noted. By looking for significant associations between the
      presence of virulence-associated genes and the pathogenicity score, we found that
      the presence of genes for invasins ibeA and gimB and for group II capsule KpsMTII
      increased virulence, while the presence of pic decreased virulence. The fact that
      ibeA, gimB and KpsMTII are characteristic of neonatal meningitis E. coli (NMEC)
      suggests that genes of NMEC in APEC increase virulence of strains. 

PMID- 23977280
TI  - Implication of IRF4 aberrant gene expression in the acute leukemias of childhood.
AB  - The most frequent targets of genetic alterations in human leukemias are
      transcription factor genes with essential functions in normal blood cell
      development. The Interferon Regulatory Factor 4 (IRF4) gene encodes a
      transcription factor important for key developmental stages of hematopoiesis,
      with known oncogenic implications in multiple myeloma, adult leukemias and
      lymphomas. Very few studies have reported an association of IRF4 with childhood
      malignancy, whereas high transcript levels have been observed in the more mature
      immunophenotype of ALL. Our aim was to investigate the expression levels of IRF4
      in the diagnostic samples of pediatric leukemias and compare them to those of
      healthy controls, in order to determine aberrant gene expression and whether it
      extends to leukemic subtypes other than the relatively mature ALL subpopulation.
      Quantitative real-time RT-PCR methodology was used to investigate IRF4 expression
      in 58 children with acute leukemias, 4 leukemic cell lines and 20 healthy
      children. We show that aberrant IRF4 gene expression is implicated in a variety
      of leukemic subtypes; higher transcript levels appear in the more immature B
      common ALL subtype and in T-cell than in B-cell leukemias, with the highest
      expression levels appearing in the AML group. Interestingly, we show that
      childhood leukemia, irrespective of subtype or cell maturation stage, is
      characterised by a minimum of approximately twice the amount of IRF4 gene
      expression encountered in healthy children. A statistically significant
      correlation also appeared to exist between high IRF4 expression and relapse. Our
      results show that ectopic expression of IRF4 follows the reverse expression
      pattern of what is encountered in normal B-cell development and that there might
      be a dose-dependency of childhood leukemia for aberrantly expressed IRF4, a
      characteristic that could be explored therapeutically. It is also suggested that
      high IRF4 expression might be used as an additional prognostic marker of relapse
      at diagnosis. 

PMID- 23977282
TI  - Phenotype and genotype analysis of Chinese patients with osteogenesis imperfecta
      type V.
AB  - Osteogenesis imperfecta (OI) type V is an autosomal-dominant disease
      characterized by calcification of the forearm interosseous membrane, radial head
      dislocation, a subphyseal metaphyseal radiodense line, and hyperplastic callus
      formation. The causative mutation, c.-14C>T in the 5'-untranslated region of
      IFITM5, was recently discovered to be involved in this disease. However, in spite
      of the little genotypic variability, considerable phenotypic variability has been
      recognized in two cohorts of patients, the majority of whom were Caucasians.
      Using exome sequencing, we identified the same heterozygous mutation in four
      Chinese families with OI type V. This study confirms the molecular cause of OI
      type V and describes the phenotype of Chinese patients with this disorder. In
      conclusion, the phenotype of Chinese patients was generally similar to that of
      Caucasian patients. 

PMID- 23977281
TI  - Cluster-based statistics for brain connectivity in correlation with behavioral
      measures.
AB  - Graph theoretical approaches have successfully revealed abnormality in brain
      connectivity, in particular, for contrasting patients from healthy controls.
      Besides the group comparison analysis, a correlational study is also challenging.
      In studies with patients, for example, finding brain connections that indeed
      deepen specific symptoms is interesting. The correlational study is also
      beneficial since it does not require controls, which are often difficult to find,
      especially for old-age patients with cognitive impairment where controls could
      also have cognitive deficits due to normal ageing. However, one of the major
      difficulties in such correlational studies is too conservative multiple
      comparison correction. In this paper, we propose a novel method for identifying
      brain connections that are correlated with a specific cognitive behavior by
      employing cluster-based statistics, which is less conservative than other
      methods, such as Bonferroni correction, false discovery rate procedure, and
      extreme statistics. Our method is based on the insight that multiple brain
      connections, rather than a single connection, are responsible for abnormal
      behaviors. Given brain connectivity data, we first compute a partial correlation
      coefficient between every edge and the behavioral measure. Then we group together
      neighboring connections with strong correlation into clusters and calculate their
      maximum sizes. This procedure is repeated for randomly permuted assignments of
      behavioral measures. Significance levels of the identified sub-networks are
      estimated from the null distribution of the cluster sizes. This method is
      independent of network construction methods: either structural or functional
      network can be used in association with any behavioral measures. We further
      demonstrated the efficacy of our method using patients with subcortical vascular
      cognitive impairment. We identified sub-networks that are correlated with the
      disease severity by exploiting diffusion tensor imaging techniques. The
      identified sub-networks were consistent with the previous clinical findings
      having valid significance level, while other methods did not assert any
      significant findings. 

PMID- 23977283
TI  - Dual-specificity phosphatase 10 controls brown adipocyte differentiation by
      modulating the phosphorylation of p38 mitogen-activated protein kinase.
AB  - BACKGROUND: Brown adipocytes play an important role in regulating the balance of
      energy, and as such, there is a strong correlation between obesity and the amount
      of brown adipose tissue. Although the molecular mechanism underlying white
      adipocyte differentiation has been well characterized, brown adipocyte
      differentiation has not been studied extensively. Here, we investigate the
      potential role of dual-specificity phosphatase 10 (DUSP10) in brown adipocyte
      differentiation using primary brown preadipocytes. METHODS AND RESULTS: The
      expression of DUSP10 increased continuously after the brown adipocyte
      differentiation of mouse primary brown preadipocytes, whereas the phosphorylation
      of p38 was significantly upregulated at an early stage of differentiation
      followed by steep downregulation. The overexpression of DUSP10 induced a decrease
      in the level of p38 phosphorylation, resulting in lower lipid accumulation than
      that in cells overexpressing the inactive mutant DUSP10. The expression levels of
      several brown adipocyte markers such as PGC-1alpha, UCP1, and PRDM16 were also
      significantly reduced upon the ectopic expression of DUSP10. Furthermore,
      decreased mitochondrial DNA content was detected in cells expressing DUSP10. The
      results obtained upon treatment with the p38 inhibitor, SB203580, clearly
      indicated that the phosphorylation of p38 at an early stage is important in brown
      adipocyte differentiation. The effect of the p38 inhibitor was partially
      recovered by DUSP10 knockdown using RNAi. CONCLUSIONS: These results suggest that
      p38 phosphorylation is controlled by DUSP10 expression. Furthermore, p38
      phosphorylation at an early stage is critical in brown adipocyte differentiation.
      Thus, the regulation of DUSP10 activity affects the efficiency of brown
      adipogenesis. Consequently, DUSP10 can be used as a novel target protein for the
      regulation of obesity.

PMID- 23977284
TI  - Magnetostatic Field System for uniform cell cultures exposure.
AB  - The aim of the present work has been the design and the realization of a
      Magnetostatic Field System for Exposure of Cell cultures (MaFiSEC) for the
      uniform and the reproducible exposure of cell cultures to static magnetic fields
      (SMFs) of moderate magnetic induction. Experimental and computer-simulated
      physical measurements show that MaFiSEC: i) generates a SMF with magnetic
      induction that can be chosen in the range of 3 to 20 mT; ii) allows the uniform
      SMF exposure of cells growing in adhesion and in suspension; iii) is cheap and
      easy to use. The efficacy and reproducibility of MaFiSEC has been tested by
      comparing the biological effects exerted on isolated human lymphocytes by 72 h of
      exposure to a magnet (i.e. Neodymium Magnetic Disk, NMD) placed under the culture
      Petri dish. Lymphocytes morphology, viability, cell death, oxidative stress and
      lysosomes activity were the parameters chosen to evaluate the SMF biological
      effects. The continuous exposure of cells to a uniform SMF, achieved with
      MaFiSEC, allows highly reproducible biochemical and morphological data. 

PMID- 23977285
TI  - Geptop: a gene essentiality prediction tool for sequenced bacterial genomes based
      on orthology and phylogeny.
AB  - Integrative genomics predictors, which score highly in predicting bacterial
      essential genes, would be unfeasible in most species because the data sources are
      limited. We developed a universal approach and tool designated Geptop, based on
      orthology and phylogeny, to offer gene essentiality annotations. In a series of
      tests, our Geptop method yielded higher area under curve (AUC) scores in the
      receiver operating curves than the integrative approaches. In the ten-fold cross
      validations among randomly upset samples, Geptop yielded an AUC of 0.918, and in
      the cross-organism predictions for 19 organisms Geptop yielded AUC scores between
      0.569 and 0.959. A test applied to the very recently determined essential gene
      dataset from the Porphyromonas gingivalis, which belongs to a phylum different
      with all of the above 19 bacterial genomes, gave an AUC of 0.77. Therefore,
      Geptop can be applied to any bacterial species whose genome has been sequenced.
      Compared with the essential genes uniquely identified by the lethal screening,
      the essential genes predicted only by Gepop are associated with more protein
      protein interactions, especially in the three bacteria with lower AUC scores
      (<0.7). This may further illustrate the reliability and feasibility of our method
      in some sense. The web server and standalone version of Geptop are available at
      http://cefg.uestc.edu.cn/geptop/ free of charge. The tool has been run on 968
      bacterial genomes and the results are accessible at the website. 

PMID- 23977287
TI  - Combined enzymatic and physical deinking methodology for efficient eco-friendly
      recycling of old newsprint.
AB  - BACKGROUND: The development in the deinking process has made recycled fiber a
      major part of the raw material for pulp and paper industry. Enzymes have
      revolutionized the deinking process obtaining brightness levels surpassing
      conventional deinking processes. This study explores the deinking efficiencies of
      bacterial alkalophilic laccase (L) and xylanase (X) enzymes along with physical
      deinking methods of microwaving (MW) and sonication (S) for recycling of old
      newsprint (ONP). METHODS AND RESULTS: The operational parameters viz. enzyme
      dose, pH and treatment time for X and L deinking were optimized statistically
      using Response Surface Methodology. Laccase did not require any mediator
      supplementation for deinking. Deinking of ONP pulp with a combination of xylanase
      and laccase enzymes was investigated, and fiber surface composition and
      morphological changes were studied using X-ray diffraction, fourier transform
      infrared spectroscopy and scanning electron microscopy. Compared to the pulp
      deinked with xylanase (47.9%) or laccase (62.2%) individually, the percentage
      reduction of effective residual ink concentration (ERIC) was higher for the
      combined xylanase/laccase-deinked pulp (65.8%). An increase in brightness
      (21.6%), breaking length (16.5%), burst factor (4.2%) tear factor (6.9%),
      viscosity (13%) and cellulose crystallinity (10.3%) along with decrease in kappa
      number (22%) and chemical consumption (50%) were also observed. Surface appeared
      more fibrillar along with changes in surface functional groups. A combination of
      physical and enzymatic processes (S-MW-XL) for deinking further improved
      brightness (28.8%) and decreased ERIC (73.9%) substantially. CONCLUSION: This is
      the first report on deinking of ONP with laccase without any mediator
      supplementation. XL pretreatment resulted in marked improvement in paper quality
      and a new sequence being reported for deinking (S-MW-XL) will contribute further
      in decreasing chemical consumption and making the process commercially feasible.

PMID- 23977286
TI  - Involvement of endoplasmic reticulum stress in albuminuria induced inflammasome
      activation in renal proximal tubular cells.
AB  - Albuminuria contributes to the progression of tubulointerstitial fibrosis.
      Although it has been demonstrated that ongoing albuminuria leads to tubular
      injury manifested by the overexpression of numerous proinflammatory cytokines,
      the mechanism remains largely unknown. In this study, we found that the
      inflammasome activation which has been recognized as one of the cornerstones of
      intracellular surveillance system was associated with the severity of albuminuria
      in the renal biopsies specimens. In vitro, bovine serum albumin (BSA) could also
      induce the activation of NLRP3 inflammasome in the cultured kidney epithelial
      cells (NRK-52E). Since there was a significant overlap of NLRP3 with the ER
      marker calreticulin, the ER stress provoked by BSA seemed to play a crucial role
      in the activation of inflammasome. Here, we demonstrated that the chemical
      chaperone taurine-conjugated ursodeoxycholic acid (TUDCA) which was proved to be
      an enhancer for the adaptive capacity of ER could attenuate the inflammasome
      activation induced by albuminuria not only in vitro but also in diabetic
      nephropathy. Taken together, these data suggested that ER stress seemed to play
      an important role in albuminuria-induced inflammasome activation, elimination of
      ER stress via TUDCA might hold promise as a novel avenue for preventing
      inflammasome activation ameliorating kidney epithelial cells injury induced by
      albuminuria. 

PMID- 23977288
TI  - Comparison of pathogen DNA isolation methods from large volumes of whole blood to
      improve molecular diagnosis of bloodstream infections.
AB  - For patients suffering from bloodstream infections (BSI) molecular diagnostics
      from whole blood holds promise to provide fast and adequate treatment. However,
      this approach is hampered by the need of large blood volumes. Three methods for
      pathogen DNA isolation from whole blood were compared, i.e. an enzymatic method
      (MolYsis, 1-5 ml), the novel non-enzymatic procedure (Polaris, 1-5 ml), and a
      method that does not entail removal of human DNA (Triton-Tris-EDTA EasyMAG, 200
      ul). These methods were evaluated by processing blood spiked with 0-1000 CFU/ml
      of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. Downstream
      detection was performed with real-time PCR assays. Polaris and MolYsis processing
      followed by real-time PCRs enabled pathogen detection at clinically relevant
      concentrations of 1-10 CFU/ml blood. By increasing sample volumes, concurrent
      lower cycle threshold (Ct) values were obtained at clinically relevant pathogen
      concentrations, demonstrating the benefit of using larger blood volumes. A 100%
      detection rate at a concentration of 10 CFU/ml for all tested pathogens was
      obtained with the Polaris enrichment, whereas comparatively lower detection rates
      were measured for MolYsis (50-67%) and EasyMAG (58-79%). For the samples with a
      concentration of 1 CFU/ml Polaris resulted in most optimal detection rates of 70
      75% (MolYsis 17-50% and TTE-EasyMAG 20-36%). The Polaris method was more
      reproducible, less labour intensive, and faster (45 minutes (including Qiagen DNA
      extraction) vs. 2 hours (MolYsis)). In conclusion, Polaris and MolYsis enrichment
      followed by DNA isolation and real-time PCR enables reliable and sensitive
      detection of bacteria and fungi from 5 ml blood. With Polaris results are
      available within 3 hours, showing potential for improved BSI diagnostics. 

PMID- 23977289
TI  - Neural responses to multimodal ostensive signals in 5-month-old infants.
AB  - Infants' sensitivity to ostensive signals, such as direct eye contact and infant
      directed speech, is well documented in the literature. We investigated how
      infants interpret such signals by assessing common processing mechanisms devoted
      to them and by measuring neural responses to their compounds. In Experiment 1, we
      found that ostensive signals from different modalities display overlapping
      electrophysiological activity in 5-month-old infants, suggesting that these
      signals share neural processing mechanisms independently of their modality. In
      Experiment 2, we found that the activation to ostensive signals from different
      modalities is not additive to each other, but rather reflects the presence of
      ostension in either stimulus stream. These data support the thesis that ostensive
      signals obligatorily indicate to young infants that communication is directed to
      them. 

PMID- 23977290
TI  - Substance P immunoreactivity exhibits frequent colocalization with kisspeptin and
      neurokinin B in the human infundibular region.
AB  - Neurons synthesizing neurokinin B (NKB) and kisspeptin (KP) in the hypothalamic
      arcuate nucleus represent important upstream regulators of pulsatile gonadotropin
      releasing hormone (GnRH) neurosecretion. In search of neuropeptides co-expressed
      in analogous neurons of the human infundibular nucleus (Inf), we have carried out
      immunohistochemical studies of the tachykinin peptide Substance P (SP) in autopsy
      samples from men (21-78 years) and postmenopausal (53-83 years) women.
      Significantly higher numbers of SP-immunoreactive (IR) neurons and darker
      labeling were observed in the Inf of postmenopausal women than in age-matched
      men. Triple-immunofluorescent studies localized SP immunoreactivity to
      considerable subsets of KP-IR and NKB-IR axons and perikarya in the infundibular
      region. In postmenopausal women, 25.1% of NKB-IR and 30.6% of KP-IR perikarya
      contained SP and 16.5% of all immunolabeled cell bodies were triple-labeled.
      Triple-, double- and single-labeled SP-IR axons innervated densely the portal
      capillaries of the infundibular stalk. In quadruple-labeled sections, these axons
      formed occasional contacts with GnRH-IR axons. Presence of SP in NKB and KP
      neurons increases the functional complexity of the putative pulse generator
      network. First, it is possible that SP modulates the effects of KP and NKB in axo
      somatic and axo-dendritic afferents to GnRH neurons. Intrinsic SP may also affect
      the activity and/or neuropeptide release of NKB and KP neurons via
      autocrine/paracrine actions. In the infundibular stalk, SP may influence the KP
      and NKB secretory output via additional autocrine/paracrine mechanisms or
      regulate GnRH neurosecretion directly. Finally, possible co-release of SP with KP
      and NKB into the portal circulation could underlie further actions on
      adenohypophysial gonadotrophs. 

PMID- 23977291
TI  - White matter deficits in psychopathic offenders and correlation with factor
      structure.
AB  - Psychopathic offenders show a persistent pattern of emotional unresponsivity to
      the often horrendous crimes they perpetrate. Recent studies have related
      psychopathy to alterations in white matter. Therefore, diffusion tensor imaging
      followed by tract-based spatial statistics (TBSS) analysis in 11 psychopathic
      offenders matched to 11 healthy controls was completed. Fractional anisotropy was
      calculated within each voxel and comparisons were made between groups using a
      permutation test. Any clusters of white matter voxels different between groups
      were submitted to probabilistic tractography. Significant differences in
      fractional anisotropy were found between psychopathic offenders and healthy
      controls in three main white matter clusters. These three clusters represented
      two major networks: an amygdalo-prefrontal network, and a striato-thalamo-frontal
      network. The interpersonal/affective component of the PCL-R correlated with white
      matter deficits in the orbitofrontal cortex and frontal pole whereas the
      antisocial component correlated with deficits in the striato-thalamo-frontal
      network. In addition to replicating earlier work concerning disruption of an
      amygdala-prefrontal network, we show for the first time that white matter
      integrity in a striato-thalamo-frontal network is disrupted in psychopathic
      offenders. The novelty of our findings lies in the two dissociable white matter
      networks that map directly onto the two major factors of psychopathy. 

PMID- 23977292
TI  - Matrix-assisted laser desorption ionization--time of flight mass spectrometry: an
      emerging tool for the rapid identification of mosquito vectors.
AB  - BACKGROUND: The identification of mosquito vectors is typically based on
      morphological characteristics using morphological keys of determination, which
      requires entomological expertise and training. The use of protein profiling by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS), which is increasingly being used for the routine identification
      of bacteria, has recently emerged for arthropod identification. METHODS: To
      investigate the usefulness of MALDI-TOF-MS as a mosquito identification tool, we
      tested protein extracts made from mosquito legs to create a database of reference
      spectra. The database included a total of 129 laboratory-reared and field-caught
      mosquito specimens consisting of 20 species, including 4 Aedes spp., 9 Anopheles
      spp., 4 Culex spp., Lutzia tigripes, Orthopodomyia reunionensis and Mansonia
      uniformis. For the validation study, blind tests were performed with 76 specimens
      consisting of 1 to 4 individuals per species. A cluster analysis was carried out
      using the MALDI-Biotyper and some spectra from all mosquito species tested.
      RESULTS: Biomarker mass sets containing 22 and 43 masses have been detected from
      100 specimens of the Anopheles, Aedes and Culex species. By carrying out 3 blind
      tests, we achieved the identification of mosquito vectors at the species level,
      including the differentiation of An. gambiae complex, which is possible using
      MALDI-TOF-MS with 1.8 as the cut-off identification score. A cluster analysis
      performed with all available mosquito species showed that MALDI-Biotyper can
      distinguish between specimens at the subspecies level, as demonstrated for An
      gambiae M and S, but this method cannot yet be considered a reliable tool for the
      phylogenetic study of mosquito species. CONCLUSIONS: We confirmed that even
      without any specific expertise, MALDI-TOF-MS profiling of mosquito leg protein
      extracts can be used for the rapid identification of mosquito vectors. Therefore,
      MALDI-TOF-MS is an alternative, efficient and inexpensive tool that can
      accurately identify mosquitoes collected in the field during entomological
      surveys.

PMID- 23977293
TI  - IP-10 is a potential biomarker of cystic fibrosis acute pulmonary exacerbations.
AB  - BACKGROUND: Cystic fibrosis (CF) is characterized by acute pulmonary
      exacerbations (APE). The CF nasal airway exhibits a similar ion transport defect
      as the lung, and colonization, infection, and inflammation within the nasal
      passages are common among CF patients. Nasal lavage fluid (NLF) is a minimally
      invasive means to collect upper airway samples. METHODS: We collected NLF at the
      onset and resolution of CF APE and compared a 27-plex cytokine profile to stable
      CF outpatients and normal controls. We also tested IP-10 levels in the
      bronchoalveolar lavage fluid (BALF) of CF patients. Well-differentiated murine
      sinonasal monolayers were exposed to bacterial stimulus, and IP-10 levels were
      measured to test epithelial secretion. RESULTS: Subjects hospitalized for APE had
      elevated IP-10 (2582 pg/mL [95% CL of mean: 818,8165], N=13) which significantly
      decreased (647 pg/mL [357,1174], P<0.05, N =13) following antimicrobial therapy.
      Stable CF outpatients exhibited intermediately elevated levels (680 pg/mL
      [281,1644], N=13) that were less than CF inpatients upon admission (P=0.056) but
      not significantly different than normal controls (342 pg/mL [110,1061]; P=0.3,
      N=10). IP-10 was significantly increased in CF BALF (2673 pg/mL [1306,5458],
      N=10) compared to healthy post-lung transplant patients (8.4 pg/mL [0.03,2172],
      N=5, P<0.001). IP-10 levels from well-differentiated CF murine nasal epithelial
      monolayers exposed to Pseudomonas PAO-1 bacteria-free prep or LPS (100 nM)
      apically for 24 hours were significantly elevated (1159 +/- 147, P<0.001 for PAO
      1; 1373 +/- 191, P<0.001 for LPS vs. 305 +/- 68 for vehicle controls). Human sino
      nasal epithelial cells derived from CF patients had a similar response to LPS
      (34% increase, P<0.05, N=6). CONCLUSIONS: IP-10 is elevated in the nasal lavage
      of CF patients with APE and responds to antimicrobial therapy. IP-10 is induced
      by airway epithelia following stimulation with bacterial pathogens in a murine
      model. Additional research regarding IP-10 as a potential biomarker is warranted.

PMID- 23977296
TI  - Are regional habitat models useful at a local-scale? A case study of threatened
      and common insectivorous bats in South-Eastern Australia.
AB  - Habitat modelling and predictive mapping are important tools for conservation
      planning, particularly for lesser known species such as many insectivorous bats.
      However, the scale at which modelling is undertaken can affect the predictive
      accuracy and restrict the use of the model at different scales. We assessed the
      validity of existing regional-scale habitat models at a local-scale and
      contrasted the habitat use of two morphologically similar species with differing
      conservation status (Mormopterus norfolkensis and Mormopterus species 2). We used
      negative binomial generalised linear models created from indices of activity and
      environmental variables collected from systematic acoustic surveys. We found that
      habitat type (based on vegetation community) best explained activity of both
      species, which were more active in floodplain areas, with most foraging activity
      recorded in the freshwater wetland habitat type. The threatened M. norfolkensis
      avoided urban areas, which contrasts with M. species 2 which occurred frequently
      in urban bushland. We found that the broad habitat types predicted from local
      scale models were generally consistent with those from regional-scale models.
      However, threshold-dependent accuracy measures indicated a poor fit and we advise
      caution be applied when using the regional models at a fine scale, particularly
      when the consequences of false negatives or positives are severe. Additionally,
      our study illustrates that habitat type classifications can be important
      predictors and we suggest they are more practical for conservation than complex
      combinations of raw variables, as they are easily communicated to land managers. 

PMID- 23977294
TI  - The mini-chromosome maintenance (Mcm) complexes interact with DNA polymerase
      alpha-primase and stimulate its ability to synthesize RNA primers.
AB  - The Mini-chromosome maintenance (Mcm) proteins are essential as central
      components for the DNA unwinding machinery during eukaryotic DNA replication. DNA
      primase activity is required at the DNA replication fork to synthesize short RNA
      primers for DNA chain elongation on the lagging strand. Although direct physical
      and functional interactions between helicase and primase have been known in many
      prokaryotic and viral systems, potential interactions between helicase and
      primase have not been explored in eukaryotes. Using purified Mcm and DNA primase
      complexes, a direct physical interaction is detected in pull-down assays between
      the Mcm2~7 complex and the hetero-dimeric DNA primase composed of the p48 and p58
      subunits. The Mcm4/6/7 complex co-sediments with the primase and the DNA
      polymerase alpha-primase complex in glycerol gradient centrifugation and forms a
      Mcm4/6/7-primase-DNA ternary complex in gel-shift assays. Both the Mcm4/6/7 and
      Mcm2~7 complexes stimulate RNA primer synthesis by DNA primase in vitro. However,
      primase inhibits the Mcm4/6/7 helicase activity and this inhibition is abolished
      by the addition of competitor DNA. In contrast, the ATP hydrolysis activity of
      Mcm4/6/7 complex is not affected by primase. Mcm and primase proteins mutually
      stimulate their DNA-binding activities. Our findings indicate that a direct
      physical interaction between primase and Mcm proteins may facilitate priming
      reaction by the former protein, suggesting that efficient DNA synthesis through
      helicase-primase interactions may be conserved in eukaryotic chromosomes.

PMID- 23977295
TI  - Examining complexity across domains: relating subjective and objective measures
      of affective environmental scenes, paintings and music.
AB  - Subjective complexity has been found to be related to hedonic measures of
      preference, pleasantness and beauty, but there is no consensus about the nature
      of this relationship in the visual and musical domains. Moreover, the affective
      content of stimuli has been largely neglected so far in the study of complexity
      but is crucial in many everyday contexts and in aesthetic experiences. We thus
      propose a cross-domain approach that acknowledges the multidimensional nature of
      complexity and that uses a wide range of objective complexity measures combined
      with subjective ratings. In four experiments, we employed pictures of affective
      environmental scenes, representational paintings, and Romantic solo and chamber
      music excerpts. Stimuli were pre-selected to vary in emotional content
      (pleasantness and arousal) and complexity (low versus high number of elements).
      For each set of stimuli, in a between-subjects design, ratings of familiarity,
      complexity, pleasantness and arousal were obtained for a presentation time of 25
      s from 152 participants. In line with Berlyne's collative-motivation model,
      statistical analyses controlling for familiarity revealed a positive relationship
      between subjective complexity and arousal, and the highest correlations were
      observed for musical stimuli. Evidence for a mediating role of arousal in the
      complexity-pleasantness relationship was demonstrated in all experiments, but was
      only significant for females with regard to music. The direction and strength of
      the linear relationship between complexity and pleasantness depended on the
      stimulus type and gender. For environmental scenes, the root mean square contrast
      measures and measures of compressed file size correlated best with subjective
      complexity, whereas only edge detection based on phase congruency yielded
      equivalent results for representational paintings. Measures of compressed file
      size and event density also showed positive correlations with complexity and
      arousal in music, which is relevant for the discussion on which aspects of
      complexity are domain-specific and which are domain-general. 

PMID- 23977297
TI  - Theoretical insights into catalytic mechanism of protein arginine
      methyltransferase 1.
AB  - Protein arginine methyltransferase 1 (PRMT1), the major arginine asymmetric
      dimethylation enzyme in mammals, is emerging as a potential drug target for
      cancer and cardiovascular disease. Understanding the catalytic mechanism of PRMT1
      will facilitate inhibitor design. However, detailed mechanisms of the methyl
      transfer process and substrate deprotonation of PRMT1 remain unclear. In this
      study, we present a theoretical study on PRMT1 catalyzed arginine dimethylation
      by employing molecular dynamics (MD) simulation and quantum mechanics/molecular
      mechanics (QM/MM) calculation. Ternary complex models, composed of PRMT1, peptide
      substrate, and S-adenosyl-methionine (AdoMet) as cofactor, were constructed and
      verified by 30-ns MD simulation. The snapshots selected from the MD trajectory
      were applied for the QM/MM calculation. The typical SN2-favored transition states
      of the first and second methyl transfers were identified from the potential
      energy profile. Deprotonation of substrate arginine occurs immediately after
      methyl transfer, and the carboxylate group of E144 acts as proton acceptor.
      Furthermore, natural bond orbital analysis and electrostatic potential
      calculation showed that E144 facilitates the charge redistribution during the
      reaction and reduces the energy barrier. In this study, we propose the detailed
      mechanism of PRMT1-catalyzed asymmetric dimethylation, which increases insight on
      the small-molecule effectors design, and enables further investigations into the
      physiological function of this family. 

PMID- 23977298
TI  - Functional genomic analyses of two morphologically distinct classes of Drosophila
      sensory neurons: post-mitotic roles of transcription factors in dendritic
      patterning.
AB  - BACKGROUND: Neurons are one of the most structurally and functionally diverse
      cell types found in nature, owing in large part to their unique class specific
      dendritic architectures. Dendrites, being highly specialized in receiving and
      processing neuronal signals, play a key role in the formation of functional
      neural circuits. Hence, in order to understand the emergence and assembly of a
      complex nervous system, it is critical to understand the molecular mechanisms
      that direct class specific dendritogenesis. METHODOLOGY/PRINCIPAL FINDINGS: We
      have used the Drosophila dendritic arborization (da) neurons to gain systems
      level insight into dendritogenesis by a comparative study of the morphologically
      distinct Class-I (C-I) and Class-IV (C-IV) da neurons. We have used a combination
      of cell-type specific transcriptional expression profiling coupled to a targeted
      and systematic in vivo RNAi functional validation screen. Our comparative
      transcriptomic analyses have revealed a large number of differentially
      enriched/depleted gene-sets between C-I and C-IV neurons, including a broad range
      of molecular factors and biological processes such as proteolytic and metabolic
      pathways. Further, using this data, we have identified and validated the role of
      37 transcription factors in regulating class specific dendrite development using
      in vivo class-specific RNAi knockdowns followed by rigorous and quantitative
      neurometric analysis. CONCLUSIONS/SIGNIFICANCE: This study reports the first
      global gene-expression profiles from purified Drosophila C-I and C-IV da neurons.
      We also report the first large-scale semi-automated reconstruction of over 4,900
      da neurons, which were used to quantitatively validate the RNAi screen
      phenotypes. Overall, these analyses shed global and unbiased novel insights into
      the molecular differences that underlie the morphological diversity of distinct
      neuronal cell-types. Furthermore, our class-specific gene expression datasets
      should prove a valuable community resource in guiding further investigations
      designed to explore the molecular mechanisms underlying class specific neuronal
      patterning.

PMID- 23977299
TI  - Tissue plasminogen activator in trabecular meshwork attenuates steroid induced
      outflow resistance in mice.
AB  - Tissue plasminogen activator, a serine protease encoded by the PLAT gene is
      present in the trabecular meshwork (TM) and other ocular tissues and has been
      reported to be downregulated by treatment with steroids in vitro. Steroids are
      known to cause changes in outflow facility of aqueous humor in many species. In
      the present study, we tested whether overexpression of PLAT can prevent and/or
      reverse the outflow facility of mouse eyes treated with steroids. Animals
      received bilateral injection with 20 ul of triamcinolone acetonide (TA) (40
      mg/ml) suspension subconjunctivally to induce outflow facility changes. Some
      animals received unilateral intracameral injection with 2 ul of adenoviral
      suspension [3-4 x 10(12) virus genomes per milliliter (vg/ml)] carrying sheep
      PLAT cDNA (AdPLAT) either concurrently with TA injection or one week after TA
      injection, whereas others received bilateral intracameral injection with 2 ul of
      adenoviral suspension (9 x 10(12) vg/ml) carrying no transgene (AdNull)
      concurrently with TA injection. Animals were sacrificed one week after AdPLAT or
      AdNull treatment. Endogenous mRNA expression levels of mouse PAI-1 and MMP-2, -9
      and -13 were also measured using qRT-PCR. Outflow facility one week after AdPLAT
      administration was increased by 60% and 63% respectively for animals that had not
      or had been pretreated with steroids. Overexpression of PLAT significantly
      upregulated expression of PAI-1, MMP-2, -9 and -13 compared to the levels found
      in TA only treated eyes. These findings suggest that overexpression of PLAT in TM
      of mouse eyes can both prevent and reverse the decrease in outflow facility
      caused by steroid treatment and is associated with upregulation of MMPs.

PMID- 23977300
TI  - Ecological niche modeling of Bacillus anthracis on three continents: evidence for
      genetic-ecological divergence?
AB  - We modeled the ecological niche of a globally successful Bacillus anthracis
      sublineage in the United States, Italy and Kazakhstan to better understand the
      geographic distribution of anthrax and potential associations between regional
      populations and ecology. Country-specific ecological-niche models were developed
      and reciprocally transferred to the other countries to determine if pathogen
      presence could be accurately predicted on novel landscapes. Native models
      accurately predicted endemic areas within each country, but transferred models
      failed to predict known occurrences in the outside countries. While the effects
      of variable selection and limitations of the genetic data should be considered,
      results suggest differing ecological associations for the B. anthracis
      populations within each country and may reflect niche specialization within the
      sublineage. Our findings provide guidance for developing accurate ecological
      niche models for this pathogen; models should be developed regionally, on the
      native landscape, and with consideration to population genetics. Further genomic
      analysis will improve our understanding of the genetic-ecological dynamics of B.
      anthracis across these countries and may lead to more refined predictive models
      for surveillance and proactive vaccination programs. Further studies should
      evaluate the impact of variable selection of native and transferred models. 

PMID- 23977301
TI  - Molecular test to assign individuals within the Cacopsylla pruni complex.
AB  - Crop protection requires the accurate identification of disease vectors, a task
      that can be made difficult when these vectors encompass cryptic species. Here we
      developed a rapid molecular diagnostic test to identify individuals of
      Cacopsyllapruni (Scopoli, 1763) (Hemiptera: Psyllidae), the main vector of the
      European stone fruit yellows phytoplasma. This psyllid encompasses two highly
      divergent genetic groups that are morphologically similar and that are
      characterized by genotyping several microsatellite markers, a costly and time
      consuming protocol. With the aim of developing species-specific PCR primers, we
      sequenced the Internal Transcribed Spacer 2 (ITS2) on a collection of C. pruni
      samples from France and other European countries. ITS2 sequences showed that the
      two genetic groups represent two highly divergent clades. This enabled us to
      develop specific primers for the assignment of individuals to either genetic
      group in a single PCR, based on ITS2 amplicon size. All previously assigned
      individuals yielded bands of expected sizes, and the PCR proved efficient on a
      larger sample of 799 individuals. Because none appeared heterozygous at the ITS2
      locus (i.e., none produced two bands), we inferred that the genetic groups of C.
      pruni, whose distribution is partly sympatric, constitute biological species that
      have not exchanged genes for an extended period of time. Other psyllid species
      (Cacopsylla, Psylla, Triozidae and Aphalaridae) failed to yield any amplicon.
      These primers are therefore unlikely to produce false positives and allow rapid
      assignment of C. pruni individuals to either cryptic species. 

PMID- 23977304
TI  - Two failures to replicate high-performance-goal priming effects.
AB  - Bargh et al. (2001) reported two experiments in which people were exposed to
      words related to achievement (e.g., strive, attain) or to neutral words, and then
      performed a demanding cognitive task. Performance on the task was enhanced after
      exposure to the achievement related words. Bargh and colleagues concluded that
      better performance was due to the achievement words having activated a "high
      performance goal". Because the paper has been cited well over 1100 times, an
      attempt to replicate its findings would seem warranted. Two direct replication
      attempts were performed. Results from the first experiment (n = 98) found no
      effect of priming, and the means were in the opposite direction from those
      reported by Bargh and colleagues. The second experiment followed up on the
      observation by Bargh et al. (2001) that high-performance-goal priming was
      enhanced by a 5-minute delay between priming and test. Adding such a delay, we
      still found no evidence for high-performance-goal priming (n = 66). These
      failures to replicate, along with other recent results, suggest that the
      literature on goal priming requires some skeptical scrutiny. 

PMID- 23977302
TI  - Identification of novel autoantibodies for detection of malignant mesothelioma.
AB  - BACKGROUND: The malignant mesothelioma (MM) survival rate has been hampered by
      the lack of efficient and accurate early detection methods. The immune system may
      detect the early changes of tumor progression by responding with tumor-associated
      autoantibody production. Hence, in this study, we translated the humoral immune
      response to cancer proteins into a potential blood test for MM.
      METHODOLOGY/PRINCIPAL FINDINGS: A T7 phage MM cDNA library was constructed using
      MM tumor tissues and biopanned for tumor-associated antigens (TAAs) using pooled
      MM patient and normal serum samples. About 1008 individual phage TAA clones from
      the biopanned library were subjected to protein microarray construction and
      tested with 53 MM and 52 control serum samples as a training group. Nine
      candidate autoantibody markers were selected from the training group using Tclass
      system and logistic regression statistical analysis, which achieved 94.3%
      sensitivity and 90.4% specificity with an AUC value of 0.89 in receiver operating
      characteristic analysis. The classifier was further evaluated with 50 patient and
      50 normal serum samples as an independent blind validation, and the sensitivity
      of 86.0% and the specificity of 86.0% were obtained with an AUC of 0.82.
      Sequencing and BLASTN analysis of the classifier revealed that five of these nine
      candidate markers were found to have strong homology to cancer related proteins
      (PDIA6, MEG3, SDCCAG3, IGHG3, IGHG1). CONCLUSIONS/SIGNIFICANCE: Our results
      indicated that using a panel of 9 autoantibody markers presented a promising
      accuracy for MM detection. Although the results need further validation in high
      risk groups, they provided the potentials in developing a serum-based assay for
      MM diagnosis.

PMID- 23977303
TI  - Bcl-2 promoter sequence G-quadruplex interactions with three planar and non
      planar cationic porphyrins: TMPyP4, TMPyP3, and TMPyP2.
AB  - The interactions of three related cationic porphyrins, TMPyP4, TMPyP3 and TMPyP2,
      with a WT 39-mer Bcl-2 promoter sequence G-quadruplex were studied using Circular
      Dichroism, ESI mass spectrometry, Isothermal Titration Calorimetry, and
      Fluorescence spectroscopy. The planar cationic porphyrin TMPyP4 (5, 10, 15, 20
      meso-tetra (N-methyl-4-pyridyl) porphine) is shown to bind to a WT Bcl-2 G
      quadruplex via two different binding modes, an end binding mode and a weaker mode
      attributed to intercalation. The related non-planar ligands, TMPyP3 and TMPyP2,
      are shown to bind to the Bcl-2 G-quadruplex by a single mode. ESI mass
      spectrometry experiments confirmed that the saturation stoichiometry is 4:1 for
      the TMPyP4 complex and 2:1 for the TMPyP2 and TMPyP3 complexes. ITC experiments
      determined that the equilibrium constant for formation of the (TMPyP4)1/DNA
      complex (K1 = 3.7 * 10(6)) is approximately two orders of magnitude greater than
      the equilibrium constant for the formation of the (TMPyP2)1/DNA complex, (K1 =
      7.0 * 10(4)). Porphyrin fluorescence is consistent with intercalation in the case
      of the (TMPyP4)3/DNA and (TMPyP4)4/DNA complexes. The non-planar shape of the
      TMPyP2 and TMPyP3 molecules results in both a reduced affinity for the end
      binding interaction and the elimination of the intercalation binding mode. 

PMID- 23977305
TI  - Enhanced osteogenesis of adipose derived stem cells with Noggin suppression and
      delivery of BMP-2.
AB  - Bone morphogenetic proteins (BMPs) are believed to be the most potent
      osteoinductive factors. However, BMPs are highly pleiotropic molecules and their
      supra-physiological high dose requirement leads to adverse side effects and
      inefficient bone formation. Thus, there is a need to develop alternative
      osteoinductive growth factor strategies that can effectively complement BMP
      activity. In this study, we intrinsically stimulated BMP signaling in adipose
      derived stem cells (ASCs) by downregulating noggin, a potent BMP antagonist,
      using an RNAi strategy. ASCs transduced with noggin shRNA significantly enhanced
      osteogenic differentiation of cells. The potency of endogenous BMPs was
      subsequently enhanced by stimulating ASCs with exogenous BMPs at a significantly
      reduced dose. The level of mineralization in noggin shRNA treated ASCs when
      treated with BMP-2 was comparable to that of control shRNA treated cell treated
      with 10-fold more BMP-2. The complementary strategy of noggin suppression + BMP-2
      to enhance osteogenesis was further confirmed in 3D in vitro environments using
      scaffolds consisting of chitosan (CH), chondroitin sulfate (CS), and apatite
      layer on their surfaces designed to slowly release BMP-2. This finding supports
      the novel therapeutic potential of this complementary strategy in bone
      regeneration. 

PMID- 23977306
TI  - Assessing interactions between the association of common genetic variant at 1p11
      (rs11249433) and hormone receptor status with breast cancer risk.
AB  - BACKGROUND: The association between rs11249433 polymorphism on 1p11 and breast
      cancer (BC) has been widely evaluated since it was first identified through
      genome-wide association approach. However, the results have been inconclusive. To
      investigate this inconsistency, we performed a meta-analysis of all available
      studies dealing with the relationship between the 1p11-rs11249433 polymorphism
      and BC. METHODS: Databases including Pubmed, SCOPUS, ISI web of knowledge, Embase
      and Cochrane databases were searched to find relevant studies. Odds ratios (ORs)
      with 95% confidence intervals (CIs) were used to assess the strength of
      association. The random-effects model was applied, addressing heterogeneity and
      publication bias. RESULTS: A total of 15 articles involving 90,291 cases and
      137,525 controls were included. In a combined analysis, the summary per-allele
      odds ratio (OR) for BC of 1p11-rs11249433 polymorphism was 1.09 (95% CI: 1.06
      1.12; P<10(-5)). Significant associations were also observed under dominant and
      recessive genetic models. In the subgroup analysis by ethnicity, significantly
      increased risks were found in Caucasians; whereas no significant associations
      were found among Asians and Africans. In addition, our data indicate that 1p11
      rs11249433 polymorphism is involved in BC susceptibility and confer its effect
      primarily in estrogen receptor-positive and progesterone receptor-positive
      tumors. CONCLUSIONS: In conclusion, this meta-analysis demonstrated that the G
      allele of 1p11-rs11249433 is a risk factor associated with increased breast
      cancer susceptibility, but these associations vary in different ethnic
      populations.

PMID- 23977307
TI  - Do spatially-implicit estimates of neutral migration comply with seed dispersal
      data in tropical forests?
AB  - Neutral community models have shown that limited migration can have a pervasive
      influence on the taxonomic composition of local communities even when all
      individuals are assumed of equivalent ecological fitness. Notably, the spatially
      implicit neutral theory yields a single parameter I for the immigration-drift
      equilibrium in a local community. In the case of plants, seed dispersal is
      considered as a defining moment of the immigration process and has attracted
      empirical and theoretical work. In this paper, we consider a version of the
      immigration parameter I depending on dispersal limitation from the neighbourhood
      of a community. Seed dispersal distance is alternatively modelled using a
      distribution that decreases quickly in the tails (thin-tailed Gaussian kernel)
      and another that enhances the chance of dispersal events over very long distances
      (heavily fat-tailed Cauchy kernel). Our analysis highlights two contrasting
      situations, where I is either mainly sensitive to community size (related to
      ecological drift) under the heavily fat-tailed kernel or mainly sensitive to
      dispersal distance under the thin-tailed kernel. We review dispersal distances of
      rainforest trees from field studies and assess the consistency between published
      estimates of I based on spatially-implicit models and the predictions of the
      kernel-based model in tropical forest plots. Most estimates of I were derived
      from large plots (10-50 ha) and were too large to be accounted for by a Cauchy
      kernel. Conversely, a fraction of the estimates based on multiple smaller plots
      (1 ha) appeared too small to be consistent with reported ranges of dispersal
      distances in tropical forests. Very large estimates may reflect within-plot
      habitat heterogeneity or estimation problems, while the smallest estimates likely
      imply other factors inhibiting migration beyond dispersal limitation. Our study
      underscores the need for interpreting I as an integrative index of migration
      limitation which, besides the limited seed dispersal, possibly includes habitat
      filtering or fragmentation. 

PMID- 23977308
TI  - Auxin-responsive DR5 promoter coupled with transport assays suggest separate but
      linked routes of auxin transport during woody stem development in Populus.
AB  - Polar auxin transport (PAT) is a major determinant of plant morphology and
      internal anatomy with important roles in vascular patterning, tropic growth
      responses, apical dominance and phyllotactic arrangement. Woody plants present a
      highly complex system of vascular development in which isolated bundles of xylem
      and phloem gradually unite to form concentric rings of conductive tissue. We
      generated several transgenic lines of hybrid poplar (Populus tremula x alba) with
      the auxin-responsive DR5 promoter driving GUS expression in order to visualize an
      auxin response during the establishment of secondary growth. Distinct GUS
      expression in the cambial zone and developing xylem-side derivatives supports the
      current view of this tissue as a major stream of basipetal PAT. However, we also
      found novel sites of GUS expression in the primary xylem parenchyma lining the
      outer perimeter of the pith. Strands of primary xylem parenchyma depart the stem
      as a leaf trace, and showed GUS expression as long as the leaves to which they
      were connected remained attached (i.e., until just prior to leaf abscission).
      Tissue composed of primary xylem parenchyma strands contained measurable levels
      of free indole-3-acetic acid (IAA) and showed basipetal transport of radiolabeled
      auxin ((3)H-IAA) that was both significantly faster than diffusion and highly
      sensitive to the PAT inhibitor NPA. Radiolabeled auxin was also able to move
      between the primary xylem parenchyma in the interior of the stem and the
      basipetal stream in the cambial zone, an exchange that was likely mediated by ray
      parenchyma cells. Our results suggest that (a) channeling of leaf-derived IAA
      first delineates isolated strands of pre-procambial tissue but then later shifts
      to include basipetal transport through the rapidly expanding xylem elements, and
      (b) the transition from primary to secondary vascular development is gradual,
      with an auxin response preceding the appearance of a unified and radially
      organized vascular cambium. 

PMID- 23977309
TI  - Using wind setdown and storm surge on Lake Erie to calibrate the air-sea drag
      coefficient.
AB  - The air-sea drag coefficient controls the transfer of momentum from wind to
      water. In modeling storm surge, this coefficient is a crucial parameter for
      estimating the surge height. This study uses two strong wind events on Lake Erie
      to calibrate the drag coefficient using the Coupled Ocean Atmosphere Wave
      Sediment Transport (COAWST) modeling system and the the Regional Ocean Modeling
      System (ROMS). Simulated waves are generated on the lake with Simulating WAves
      Nearshore (SWAN). Wind setdown provides the opportunity to eliminate wave setup
      as a contributing factor, since waves are minimal at the upwind shore. The study
      finds that model results significantly underestimate wind setdown and storm surge
      when a typical open-ocean formulation without waves is used for the drag
      coefficient. The contribution of waves to wind setdown and storm surge is 34.7%.
      Scattered lake ice also increases the effective drag coefficient by a factor of
      1.1. 

PMID- 23977310
TI  - Antimicrobial potential of endophytic fungi derived from three seagrass species:
      Cymodocea serrulata, Halophila ovalis and Thalassia hemprichii.
AB  - Endophytic fungi from three commonly found seagrasses in southern Thailand were
      explored for their ability to produce antimicrobial metabolites. One hundred and
      sixty endophytic fungi derived from Cymodoceaserrulata (Family Cymodoceaceae),
      Halophilaovalis and Thalassiahemprichii (Family Hydrocharitaceae) were screened
      for production of antimicrobial compounds by a colorimetric broth microdilution
      test against ten human pathogenic microorganisms including Staphylococcus aureus
      ATCC 25923, a clinical isolate of methicillin-resistant S. aureus, Escherichia
      coli ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 90028
      and NCPF 3153, Cryptococcus neoformans ATCC 90112 and ATCC 90113 and clinical
      isolates of Microsporumgypseum and Penicilliummarneffei. Sixty-nine percent of
      the isolates exhibited antimicrobial activity against at least one test strain.
      Antifungal activity was more pronounced than antibacterial activity. Among the
      active fungi, seven isolates including Hypocreales sp. PSU-ES26 from C.
      serrulata, Trichoderma spp. PSU-ES8 and PSU-ES38 from H. ovalis, and Penicillium
      sp. PSU-ES43, Fusarium sp. PSU-ES73, Stephanonectria sp. PSU-ES172 and an
      unidentified endophyte PSU-ES190 from T. hemprichii exhibited strong
      antimicrobial activity against human pathogens with minimum inhibitory
      concentrations (MIC) of less than 10 ug/ml. The inhibitory extracts at
      concentrations of 4 times their MIC destroyed the targeted cells as observed by
      scanning electron microscopy. These results showed the antimicrobial potential of
      extracts from endophytic fungi from seagrasses. 

PMID- 23977311
TI  - Anandamide levels fluctuate in the bovine oviduct during the oestrous cycle.
AB  - Mammalian oviduct acts as a reservoir for spermatozoa and provides an environment
      in which they may compete for the opportunity to fertilize the oocyte. Whilst in
      the oviduct spermatozoa undergo capacitation essential for fertilization. Sperm
      oviduct interaction is essential for sperm capacitation and is a tightly
      regulated process influenced by the local microenvironment. Previously we
      reported that the endocannabinoid anandamide (AEA) regulates sperm release from
      epithelial oviductal cells by promoting sperm capacitation. The aims of this work
      were to measure the AEA content and to characterize the main AEA metabolic
      pathway in the bovine oviduct and determine how these change through the oestrous
      cycle. In this study, the levels of AEA and two other N-acylethanolamines, N
      oleoylethanolamine and N-palmitoylethanolamine, were measured in bovine oviduct
      collected during different stages of oestrous cycle by ultra high performance
      liquid chromatography tandem mass spectrometry. Results indicated that
      intracellular oviductal epithelial levels of all three N-acylethanolamines
      fluctuate during oestrous cycle. Anandamide from oviductal fluid also varied
      during oestrous cycle, with the highest values detected during the periovulatory
      period. Endocannabinoid levels from ipsilateral oviduct to ovulation were higher
      than those detected in the contralateral one, suggesting that levels of oviductal
      AEA may be regulated by ovarian hormones. The expression and localization of N
      acylethanolamines metabolizing enzymes in bovine oviduct were also determined by
      RT-PCR, Western blot, and immunohistochemistry but no change was found during the
      oestrous cycle. Furthermore, nanomolar levels of AEA were detected in follicular
      fluids, suggesting that during ovulation the mature follicle may contribute to
      oviductal AEA levels to create an endocannabinoid gradient conducive to the
      regulation of sperm function for successful fertilization. 

PMID- 23977312
TI  - Brain-immune interaction accompanying odor-evoked autobiographic memory.
AB  - The phenomenon in which a certain smell evokes a specific memory is known as the
      Proust phenomenon. Odor-evoked autobiographic memories are more emotional than
      those elicited by other sensory stimuli. The results of our previous study
      indicated that odor-evoked autobiographic memory accompanied by positive emotions
      has remarkable effects on various psychological and physiological activities,
      including the secretion of cytokines, which are immune-signaling molecules that
      modulate systemic inflammation. In this study, we aimed to clarify the neural
      substrates associated with the interaction between odor-evoked autobiographic
      memory and peripheral circulating cytokines. We recruited healthy male and female
      volunteers and investigated the association between brain responses and the
      concentration of several cytokines in the plasma by using positron emission
      tomography (PET) recordings when an autographic memory was evoked in participants
      by asking them to smell an odor that was nostalgic to them. Participants
      experienced positive emotions and autobiographic memories when nostalgic odors
      were presented to them. The levels of peripheral proinflammatory cytokines, such
      as the tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma),
      were significantly reduced after experiencing odor-evoked autobiographic memory.
      Subtraction analysis of PET images indicated that the medial orbitofrontal cortex
      (mOFC) and precuneus/posterior cingulate cortex (PCC) were significantly
      activated during experiences of odor-evoked autobiographic memory. Furthermore, a
      correlation analysis indicated that activities of the mOFC and precuneus/PCC were
      negatively correlated with IFN-gamma concentration. These results indicate that
      the neural networks including the precuneus/PCC and mOFC might regulate the
      secretion of peripheral proinflammatory cytokines during the experience of odor
      evoked autobiographic memories accompanied with positive emotions. 

PMID- 23977313
TI  - Control of male and female fertility by the netrin axon guidance genes.
AB  - The netrin axon guidance genes have previously been implicated in fertility in C.
      elegans and in vertebrates. Here we show that adult Drosophila lacking both
      netrin genes, NetA and NetB, have fertility defects in both sexes together with
      an inability to fly and reduced viability. NetAB females produce fertilized eggs
      at a much lower rate than wild type. Oocyte development and ovarian innervation
      are unaffected in NetAB females, and the reproductive tract appears normal. A
      small gene, hog, that resides in an intron of NetB does not contribute to the
      NetAB phenotype. Restoring endogenous NetB expression rescues egg-laying, but
      additional genetic manipulations, such as restoration of netrin midline
      expression and inhibition of cell death have no effect on fertility. NetAB males
      induce reduced egg-laying in wild type females and display mirror movements of
      their wings during courtship. Measurement of courtship parameters revealed no
      difference compared to wild type males. Transgenic manipulations failed to rescue
      male fertility and mirror movements. Additional genetic manipulations, such as
      removal of the enabled gene, a known suppressor of the NetAB embryonic CNS
      phenotype, did not improve the behavioral defects. The ability to fly was rescued
      by inhibition of neuronal cell death and pan-neural NetA expression. Based on our
      results we hypothesize that the adult fertility defects of NetAB mutants are due
      to ovulation defects in females and a failure to properly transfer sperm proteins
      in males, and are likely to involve multiple neural circuits. 

PMID- 23977314
TI  - Association between 1p11-rs11249433 polymorphism and breast cancer
      susceptibility: evidence from 15 case-control studies.
AB  - Genome-wide association studies have identified SNP rs11249433 at chromosome 1p11
      as a new breast cancer (BC) susceptibility locus in populations of European
      descent. Since then, the relationship between 1p11- rs11249433 and breast cancer
      has been reported in various ethnic groups; however, these studies have yielded
      inconsistent results. To investigate this inconsistency, we performed a meta
      analysis of 15 studies involving a total of 90,154 cases and 137,238 controls for
      1p11-rs11249433 polymorphism to evaluate its effect on genetic susceptibility for
      breast cancer. An overall random effects odds ratio of 1.09 (95% CI: 1.06-1.12,
      P<10(-5)) was found for rs11249433-G variant. Significant results were also
      observed for heterozygous (OR=1.09, 95% CI: 1.05-1.12, P<10(-5)) and homozygote
      (OR=1.14, 95% CI: 1.08-1.21, P<10(-5)). There was strong evidence of
      heterogeneity, which largely disappeared after stratification by ethnicity. After
      stratified by ethnicity, significant associations were found among Caucasians.
      However, no significant associations were detected among East Asian and African
      populations. In addition, we found that rs11249433 polymorphism on 1p11 confer
      risk, exclusively for ER-positive tumors with per-allele OR of 1.13 (95% CI: 1.08
      1.18; P <10(-5)) compared to ER-negative tumors of 1.01 (95% CI: 0.98-1.04;
      P=0.49). Similar results were also observed when stratified by PR status. Our
      findings demonstrated that rs11249433-G allele is a risk-conferring factor for
      the development of breast cancer, especially in Caucasians. 

PMID- 23977315
TI  - Trans-ethnical shift of the risk genotype in the CETP I405V with longevity: a
      Chinese case-control study and meta-analysis.
AB  - BACKGROUND: The I405V polymorphism of the cholesteryl ester transfer protein gene
      (CETP) has been suggested to be a protective factor conferring longevity in
      Ashkenazi Jews, although findings in other races are not supportive. This paper
      describes a case-control study and a meta-analysis conducted to derive a more
      precise estimation of the association between CETP 405V and longevity. METHODS:
      We enrolled 1,021 ethnic Han Chinese participants (506 in the longevity group and
      515 controls), then performed a meta-analysis that integrated the current study
      and previously published ones. Pooled odds ratios (OR) were calculated for allele
      contrasts, dominant and recessive inheritance models to assess the association
      between CETP 405V and longevity according to the ethnic stratification. RESULTS:
      Our case-control data indicated that CETP 405V is a longevity risk allele in all
      genetic models (P additive =0.008; P dominant =0.008, OR(dominant)=0.673; P
      recessive =0.017, OR(recessive)=0.654) after adjustment for the apolipoprotein E
      (APOE) epsilon4 allele, body mass index and high-density lipoprotein cholesterol.
      A synergy was detected between 405V and APOE epsilon4 (P=0.001, OR=0.530). Eight
      studies were eligible for meta-analysis, which confirmed 405V is the risky allele
      against longevity in all genetic models: allele contrasts (OR=0.81, 95%CI=0.74
      0.88), dominant model (OR=0.72, 95%CI=0.64-0.82) and recessive model (OR=0.80,
      95%CI=0.67-0.96). After ethnic stratification, 405V remained a risk allele in
      East Asians but no significant association was found in Europeans or white
      Americans. CONCLUSION: Our case-control study suggests CETP 405V as a risk allele
      against longevity in Chinese. The meta-analysis suggests the involvement of CETP
      405V is protective in Ashkenazi Jews but is a risk allele against longevity in
      the East Asian (Chinese) population.

PMID- 23977316
TI  - Increasing accessibility to the blind of virtual environments, using a virtual
      mobility aid based on the "EyeCane": feasibility study.
AB  - Virtual worlds and environments are becoming an increasingly central part of our
      lives, yet they are still far from accessible to the blind. This is especially
      unfortunate as such environments hold great potential for them for uses such as
      social interaction, online education and especially for use with familiarizing
      the visually impaired user with a real environment virtually from the comfort and
      safety of his own home before visiting it in the real world. We have implemented
      a simple algorithm to improve this situation using single-point depth
      information, enabling the blind to use a virtual cane, modeled on the "EyeCane"
      electronic travel aid, within any virtual environment with minimal pre
      processing. Use of the Virtual-EyeCane, enables this experience to potentially be
      later used in real world environments with identical stimuli to those from the
      virtual environment. We show the fast-learned practical use of this algorithm for
      navigation in simple environments. 

PMID- 23977318
TI  - Evolution and taxonomic classification of alphapapillomavirus 7 complete genomes:
      HPV18, HPV39, HPV45, HPV59, HPV68 and HPV70.
AB  - BACKGROUND: The species Alphapapillomavirus 7 (alpha-7) contains human
      papillomavirus genotypes that account for 15% of invasive cervical cancers and
      are disproportionately associated with adenocarcinoma of the cervix. Complete
      genome analyses enable identification and nomenclature of variant lineages and
      sublineages. METHODS: The URR/E6 region was sequenced to screen for novel
      variants of HPV18, 39, 45, 59, 68, 70, 85 and 97 from 1147 cervical samples
      obtained from multiple geographic regions that had previously been shown to
      contain an alpha-7 HPV isolate. To study viral heterogeneity, the complete 8 kb
      genome of 128 isolates, including 109 sequenced for this analysis, were annotated
      and analyzed. Viral evolution was characterized by constructing phylogenic trees
      using maximum-likelihood and Bayesian algorithms. Global and pairwise alignments
      were used to calculate total and ORF/region nucleotide differences; lineages and
      sublineages were assigned using an alphanumeric system. The prototype genome was
      assigned to the A lineage or A1 sublineage. RESULTS: The genomic diversity of
      alpha-7 HPV types ranged from 1.1% to 6.7% nucleotide sequence differences; the
      extent of genome-genome pairwise intratype heterogeneity was 1.1% for HPV39, 1.3%
      for HPV59, 1.5% for HPV45, 1.6% for HPV70, 2.1% for HPV18, and 6.7% for HPV68.
      ME180 (previously a subtype of HPV68) was designated as the representative genome
      for HPV68 sublineage C1. Each ORF/region differed in sequence diversity, from
      most variable to least variable: noncoding region 1 (NCR1) / noncoding region 2
      (NCR2) > upstream regulatory region (URR) > E6 / E7 > E2 / L2 > E1 / L1.
      CONCLUSIONS: These data provide estimates of the maximum viral genomic
      heterogeneity of alpha-7 HPV type variants. The proposed taxonomic system
      facilitates the comparison of variants across epidemiological and molecular
      studies. Sequence diversity, geographic distribution and phylogenetic topology of
      this clinically important group of HPVs suggest an independent evolutionary
      history for each type.

PMID- 23977317
TI  - Phospholipids induce conformational changes of SecA to form membrane-specific
      domains: AFM structures and implication on protein-conducting channels.
AB  - SecA, an essential component of the Sec machinery, exists in a soluble and a
      membrane form in Escherichia coli. Previous studies have shown that the soluble
      SecA transforms into pore structures when it interacts with liposomes, and
      integrates into membranes containing SecYEG in two forms: SecAS and SecAM; the
      latter exemplified by two tryptic membrane-specific domains, an N-terminal domain
      (N39) and a middle M48 domain (M48). The formation of these lipid-specific
      domains was further investigated. The N39 and M48 domains are induced only when
      SecA interacts with anionic liposomes. Additionally, the N-terminus, not the C
      terminus of SecA is required for inducing such conformational changes.
      Proteolytic treatment and sequence analyses showed that liposome-embedded SecA
      yields the same M48 and N39 domains as does the membrane-embedded SecA. Studies
      with chemical extraction and resistance to trypsin have also shown that these
      proteoliposome-embedded SecA fragments exhibit the same stability and
      characteristics as their membrane-embedded SecA equivalents. Furthermore, the
      cloned lipid-specific domains N39 and M48, but not N68 or C34, are able to form
      partial, but imperfect ring-like structures when they interact with
      phospholipids. These ring-like structures are characteristic of a SecA pore
      structure, suggesting that these domains contribute part of the SecA-dependent
      protein-conducting channel. We, therefore, propose a model in which SecA alone is
      capable of forming a lipid-specific, asymmetric dimer that is able to function as
      a viable protein-conducting channel in the membrane, without any requirement for
      SecYEG. 

PMID- 23977319
TI  - Molecular dynamics simulations to provide insights into epitopes coupled to the
      soluble and membrane-bound MHC-II complexes.
AB  - Epitope recognition by major histocompatibility complex II (MHC-II) is essential
      for the activation of immunological responses to infectious diseases. Several
      studies have demonstrated that this molecular event takes place in the MHC-II
      peptide-binding groove constituted by the alpha and beta light chains of the
      heterodimer. This MHC-II peptide-binding groove has several pockets (P1-P11)
      involved in peptide recognition and complex stabilization that have been probed
      through crystallographic experiments and in silico calculations. However, most of
      these theoretical calculations have been performed without taking into
      consideration the heavy chains, which could generate misleading information about
      conformational mobility both in water and in the membrane environment. Therefore,
      in absence of structural information about the difference in the conformational
      changes between the peptide-free and peptide-bound states (pMHC-II) when the
      system is soluble in an aqueous environment or non-covalently bound to a cell
      membrane, as the physiological environment for MHC-II is. In this study, we
      explored the mechanistic basis of these MHC-II components using molecular
      dynamics (MD) simulations in which MHC-II was previously co-crystallized with a
      small epitope (P7) or coupled by docking procedures to a large (P22) epitope.
      These MD simulations were performed at 310 K over 100 ns for the water-soluble
      (MHC-IIw, MHC-II-P(7w), and MHC-II-P(22w)) and 150 ns for the membrane-bound
      species (MHC-IIm, MHC-II-P(7m), and MHC-II-P(22m)). Our results reveal that
      despite the different epitope sizes and MD simulation environments, both peptides
      are stabilized primarily by residues lining P1, P4, and P6-7, and similar
      noncovalent intermolecular energies were observed for the soluble and membrane
      bound complexes. However, there were remarkably differences in the conformational
      mobility and intramolecular energies upon complex formation, causing some
      differences with respect to how the two peptides are stabilized in the peptide
      binding groove.

PMID- 23977320
TI  - Dopamine modulates acetylcholine release via octopamine and CREB signaling in
      Caenorhabditis elegans.
AB  - Animals change their behavior and metabolism in response to external stimuli.
      cAMP response element binding protein (CREB) is a signal-activated transcription
      factor that enables the coupling of extracellular signals and gene expression to
      induce adaptive changes. Biogenic amine neurotransmitters regulate CREB and such
      regulation is important for long-term changes in various nervous system
      functions, including learning and drug addiction. In Caenorhabditis elegans, the
      amine neurotransmitter octopamine activates a CREB homolog, CRH-1, in cholinergic
      SIA neurons, whereas dopamine suppresses CREB activation by inhibiting octopamine
      signaling in response to food stimuli. However, the physiological role of this
      activation is unknown. In this study, the effect of dopamine, octopamine, and
      CREB on acetylcholine signaling was analyzed using the acetylcholinesterase
      inhibitor aldicarb. Mutants with decreased dopamine signaling exhibited reduced
      acetylcholine signaling, and octopamine and CREB functioned downstream of
      dopamine in this regulation. This study demonstrates that the regulation of CREB
      by amine neurotransmitters modulates acetylcholine release from the neurons of C.
      elegans. 

PMID- 23977321
TI  - 'Candidatus Megaira polyxenophila' gen. nov., sp. nov.: considerations on
      evolutionary history, host range and shift of early divergent rickettsiae.
AB  - "Neglected Rickettsiaceae" (i.e. those harboured by non-hematophagous eukaryotic
      hosts) display greater phylogenetic variability and more widespread dispersal
      than pathogenic ones; yet, the knowledge about their actual host range and host
      shift mechanism is scarce. The present work reports the characterization
      following the full-cycle rRNA approach (SSU rRNA sequence, specific in situ
      hybridization, and ultrastructure) of a novel rickettsial bacterium, herewith
      proposed as 'Candidatus Megaira polyxenophila' gen. nov., sp. nov. We found it in
      association with four different free-living ciliates (Diophrys oligothrix,
      Euplotes octocarinatus, Paramecium caudatum, and Spirostomum sp., all belonging
      to Alveolata, Ciliophora); furthermore it was recently observed as intracellular
      occurring in Carteria cerasiformis and Pleodorina japonica (Chlorophyceae,
      Chlorophyta). Phylogenetic analyses demonstrated the belonging of the candidate
      new genus to the family Rickettsiaceae (Alphaproteobacteria, Rickettsiales) as a
      sister group of the genus Rickettsia. In situ observations revealed the ability
      of the candidate new species to colonize either nuclear or cytoplasmic
      compartments, depending on the host organism. The presence of the same bacterial
      species within different, evolutionary distant, hosts indicates that 'Candidatus
      Megaira polyxenophila' recently underwent several distinct host shifts, thus
      suggesting the existence of horizontal transmission pathways. We consider these
      findings as indicative of an unexpected spread of rickettsial infections in
      aquatic communities, possibly by means of trophic interactions, and hence propose
      a new interpretation of the origin and phylogenetic diversification of
      rickettsial bacteria. 

PMID- 23977322
TI  - Analysis of human blood plasma proteome from ten healthy volunteers from Indian
      population.
AB  - Analysis of any mammalian plasma proteome is a challenge, particularly by mass
      spectrometry, due to the presence of albumin and other abundant proteins which
      can mask the detection of low abundant proteins. As detection of human plasma
      proteins is valuable in diagnostics, exploring various workflows with minimal
      fractionation prior to mass spectral analysis, is required in order to study
      population diversity involving analysis in a large cohort of samples. Here, we
      used 'reference plasma sample', a pool of plasma from 10 healthy individuals from
      Indian population in the age group of 25-60 yrs including 5 males and 5 females.
      The 14 abundant proteins were immunodepleted from plasma and then evaluated by
      three different workflows for proteome analysis using a nanoflow reverse phase
      liquid chromatography system coupled to a LTQ Orbitrap Velos mass spectrometer.
      The analysis of reference plasma sample a) without prefractionation, b) after
      prefractionation at peptide level by strong cation exchange chromatography and c)
      after prefractionation at protein level by sodium dodecyl sulfate polyacrylamide
      gel electrophoresis, led to the identification of 194, 251 and 342 proteins
      respectively. Together, a comprehensive dataset of 517 unique proteins was
      achieved from all the three workflows, including 271 proteins with high
      confidence identified by >= 2 unique peptides in any of the workflows or
      identified by single peptide in any of the two workflows. A total of 70 proteins
      were common in all the three workflows. Some of the proteins were unique to our
      study and could be specific to Indian population. The high-confidence dataset
      obtained from our study may be useful for studying the population diversity, in
      discovery and validation process for biomarker identification.

PMID- 23977323
TI  - Intestinal-specific TNFalpha overexpression induces Crohn's-like ileitis in mice.
AB  - BACKGROUND AND AIM: Human and animal studies have clearly established tumor
      necrosis factor (TNF)alpha as an important mediator of Crohn's disease
      pathogenesis. However, whether systemic or only local TNFalpha overproduction is
      required for the development of chronic intestinal inflammation and Crohn's
      disease remains unclear. The aim of this study was to assess the contribution of
      intestinal epithelial-derived TNFalpha to the development of murine Crohn's-like
      ileitis. METHODS: We adapted the well-established TNF(?ARE/+) mouse model of
      Crohn's disease (which systemically overexpresses TNFalpha) to generate a
      homozygous mutant strain that overexpress TNFalpha only within the intestinal
      epithelium. Intestinal-specific TNF(i?ARE/i?ARE) mice were examined for
      histopathological signs of gut inflammation and extraintestinal manifestations of
      Crohn's disease. The mucosal immune phenotype was characterized, and the
      contribution of specific lymphocyte populations to the pathogenesis of
      TNF(i?ARE/i?ARE) ileitis was assessed. RESULTS: TNF(i?ARE/i?ARE) mice had
      increased mucosal and systemic TNFalpha levels compared to wild-type controls
      (P<0.001), as well as severe chronic ileitis with increased neutrophil
      infiltration and villous distortion, but no extraintestinal manifestations
      (P<0.001 vs. wild-type controls). The gut mucosal lymphocytic compartment was
      also expanded in TNF(i?ARE/i?ARE) mice (P<0.05), consisting of activated CD69(+)
      and CD4(+)CD62L(-) lymphocytes (P<0.05). FasL expression was significantly
      elevated in the mesenteric lymph nodes of TNF(i?ARE/i?ARE) mice (P<0.05).
      Adoptive transfer of mucosal TNF(i?ARE/i?ARE) lymphocytes resulted in ileitis in
      immunologically naive severe combined immunodeficiency recipients (P<0.05 vs.
      wild-type controls), indicating an effector phenotype that was associated with
      increased production of both Th1 (IFNgamma) and Th2 (IL-5, IL-13) cytokines.
      CONCLUSION: Intestinal epithelial-derived TNFalpha is sufficient for the
      induction of Crohn's-like ileitis, but not for the occurrence of extraintestinal
      manifestations, in TNF(i?ARE/i?ARE) mice. These effects were associated with
      generation of effector lymphocytes within the intestinal mucosa and dysregulated
      apoptosis. Thus, targeted intestinal blockade of TNFalpha may provide an
      effective means to neutralize gut-derived TNFalpha with reduced side effects.

PMID- 23977325
TI  - Modulation of 14-3-3/phosphotarget interaction by physiological concentrations of
      phosphate and glycerophosphates.
AB  - Molecular mechanisms governing selective binding of a huge number of various
      phosphorylated protein partners to 14-3-3 remain obscure. Phosphate can bind to
      14-3-3 and therefore being present at high intracellular concentration, which
      undergoes significant changes under physiological conditions, phosphate can
      theoretically regulate interaction of 14-3-3 with phosphorylated targets. In
      order to check this hypothesis we analyzed effect of phosphate and other natural
      abundant anions on interaction of 14-3-3 with phosphorylated human small heat
      shock protein HspB6 (Hsp20) participating in regulation of different
      intracellular processes. Inorganic phosphate, glycerol-1-phosphate and glycerol-2
      phosphate at physiologically relevant concentrations (5-15 mM) significantly
      destabilized complexes formed by 14-3-3zeta and phosphorylated HspB6 (pHspB6),
      presumably, via direct interaction with the substrate-binding site of 14-3-3.
      Phosphate also destabilized complexes between pHspB6 and 14-3-3gamma or the
      monomeric mutant form of 14-3-3zeta. Inorganic sulfate and pyrophosphate were
      less effective in modulation of 14-3-3 interaction with its target protein. The
      inhibitory effect of all anions on pHspB6/14-3-3 interaction was concentration
      dependent. It is hypothesized that physiological changes in phosphate anions
      concentration can modulate affinity and specificity of interaction of 14-3-3 with
      its multiple targets and therefore the actual phosphointeractome of 14-3-3. 

PMID- 23977324
TI  - The loss of Gnai2 and Gnai3 in B cells eliminates B lymphocyte compartments and
      leads to a hyper-IgM like syndrome.
AB  - B lymphocytes are compartmentalized within lymphoid organs. The organization of
      these compartments depends upon signaling initiated by G-protein linked
      chemoattractant receptors. To address the importance of the G-proteins Galphai2
      and Galphai3 in chemoattractant signaling we created mice lacking both proteins
      in their B lymphocytes. While bone marrow B cell development and egress is
      grossly intact; mucosal sites, splenic marginal zones, and lymph nodes
      essentially lack B cells. There is a partial block in splenic follicular B cell
      development and a 50-60% reduction in splenic B cells, yet normal numbers of
      splenic T cells. The absence of Galphai2 and Galphai3 in B cells profoundly
      disturbs the architecture of lymphoid organs with loss of B cell compartments in
      the spleen, thymus, lymph nodes, and gastrointestinal tract. This results in a
      severe disruption of B cell function and a hyper-IgM like syndrome. Beyond the
      pro-B cell stage, B cells are refractory to chemokine stimulation, and splenic B
      cells are poorly responsive to antigen receptor engagement. Galphai2 and Galphai3
      are therefore critical for B cell chemoattractant receptor signaling and for
      normal B cell function. These mice provide a worst case scenario of the
      consequences of losing chemoattractant receptor signaling in B cells. 

PMID- 23977326
TI  - The impact of physical disturbance and increased sand burial on clonal growth and
      spatial colonization of Sporobolus virginicus in a coastal dune system.
AB  - Dune plants are subjected to disturbance and environmental stresses, but little
      is known about the possible combined effects of such factors on growth and
      spatial colonization. We investigated how clones of Sporobolusvirginicus, a
      widespread dune species, responded to the independent and interactive effects of
      breakage of rhizomes, breakage position and burial regime. Horizontal rhizomes
      were severed at three different internode positions relative to the apex to span
      the range of damage by disturbance naturally observed or left intact, and apical
      portions exposed to two burial scenarios (ambient vs. increased frequency) for
      three months in the field. The performance of both parts of severed rhizomes, the
      apical portion and the remaining basal portion connected to clone containing four
      consecutive ramets, was compared with that of equivalent parts in intact
      rhizomes. Apical portions severed proximal to the third internode did not survive
      and their removal did not enhance branching on their respective basal portions.
      Severing the sixth or twelfth internode did not affect survival and rhizome
      extension of apical portions, but suppressed ramet production and reduced total
      biomass and specific shoot length. Their removal enhanced branching and ramet
      production on basal portions and changed the original rhizome growth trajectory.
      However, the gain in number of ramets in basal portions never compensated for the
      reduction in ramet number in apical portions. Recurrent burial increased biomass
      allocation to root tissues. Burial also stimulated rhizome extension only in
      intact rhizomes, indicating that disturbance interacts with, and counteracts, the
      positive burial effect. These results suggest that disturbance and recurrent
      burial in combination reduces the regeneration success and spread capacity of S.
      virginucus. Since global change leads to increasingly severe or frequent storms,
      the impact of disturbance and burial on clones could be greater in future and
      possibly prevent colonization of mobile dunes by the species. 

PMID- 23977327
TI  - New onset of constipation during long-term physical inactivity: a proof-of
      concept study on the immobility-induced bowel changes.
AB  - BACKGROUND: The pathophysiological mechanisms underlining constipation are
      incompletely understood, but prolonged bed rest is commonly considered a relevant
      determinant. AIMS: Our primary aim was to study the effect of long-term physical
      inactivity on determining a new onset of constipation. Secondary aim were the
      evaluation of changes in stool frequency, bowel function and symptoms induced by
      this prolonged physical inactivity. METHODS: Ten healthy men underwent a 7-day
      run-in followed by 35-day study of experimentally-controlled bed rest. The study
      was sponsored by the Italian Space Agency. The onset of constipation was
      evaluated according to Rome III criteria for functional constipation. Abdominal
      bloating, flatulence, pain and urgency were assessed by a 100mm Visual Analog
      Scales and bowel function by adjectival scales (Bristol Stool Form Scale, ease of
      passage of stool and sense of incomplete evacuation). Daily measurements of bowel
      movements was summarized on a weekly score. Pre and post bed rest Quality of Life
      (SF-36), general health (Goldberg's General Health) and depression mood (Zung
      scale) questionnaires were administered. RESULTS: New onset of functional
      constipation fulfilling Rome III criteria was found in 60% (6/10) of participants
      (p=0.03). The score of flatulence significantly increased whilst the stool
      frequency significantly decreased during the week-by-week comparisons period
      (repeated-measures ANOVA, p=0.02 and p=0.001, respectively). Stool consistency
      and bowel symptoms were not influenced by prolonged physical inactivity. In
      addition, no significant changes were observed in general health, in mood state
      and in quality of life at the end of bed rest. CONCLUSIONS: Our results provide
      evidence that prolonged physical inactivity is relevant etiology in functional
      constipation in healthy individuals. The common clinical suggestion of early
      mobilization in bedridden patients is supported as well.

PMID- 23977328
TI  - Sustained release of BMP-2 in bioprinted alginate for osteogenicity in mice and
      rats.
AB  - The design of bioactive three-dimensional (3D) scaffolds is a major focus in bone
      tissue engineering. Incorporation of growth factors into bioprinted scaffolds
      offers many new possibilities regarding both biological and architectural
      properties of the scaffolds. This study investigates whether the sustained
      release of bone morphogenetic protein 2 (BMP-2) influences osteogenicity of
      tissue engineered bioprinted constructs. BMP-2 loaded on gelatin microparticles
      (GMPs) was used as a sustained release system, which was dispersed in hydrogel
      based constructs and compared to direct inclusion of BMP-2 in alginate or control
      GMPs. The constructs were supplemented with goat multipotent stromal cells
      (gMSCs) and biphasic calcium phosphate to study osteogenic differentiation and
      bone formation respectively. BMP-2 release kinetics and bioactivity showed
      continuous release for three weeks coinciding with osteogenicity. Osteogenic
      differentiation and bone formation of bioprinted GMP containing constructs were
      investigated after subcutaneous implantation in mice or rats. BMP-2 significantly
      increased bone formation, which was not influenced by the release timing. We
      showed that 3D printing of controlled release particles is feasible and that the
      released BMP-2 directs osteogenic differentiation in vitro and in vivo. 

PMID- 23977329
TI  - Development of in vitro 3D TissueFlex(r) islet model for diabetic drug efficacy
      testing.
AB  - Increasing individuals diagnosed with type II diabetes pose a strong demand for
      the development of more effective anti-diabetic drugs. However, expensive,
      ethically controversial animal-based screening for anti-diabetic compounds is not
      always predictive of the human response. The use of in vitro cell-based models in
      research presents obviously ethical and cost advantages over in vivo models. This
      study was to develop an in vitro three-dimensional (3D) perfused culture model of
      islets (Islet TF) for maintaining viability and functionality longer for diabetic
      drug efficacy tests. Briefly fresh isolated rat islets were encapsulated in
      ultrapure alginate and the encapsulated islets were cultured in TissueFlex((r)),
      a multiple, parallel perfused microbioreactor system for 7 days. The encapsulated
      islets cultured statically in cell culture plates (3D static) and islets cultured
      in suspension (2D) were used as the comparisons. In this study we demonstrate for
      the first time that Islet TF model can maintain the in vitro islet viability, and
      more importantly, the elevated functionality in terms of insulin release and
      dynamic responses over a 7-day culture period. The Islet TF displays a high
      sensitivity in responding to drugs and drug dosages over conventional 2D and 3D
      static models. Actual drug administration in clinics could be simulated using the
      developed Islet TF model, and the patterns of insulin release response to the
      tested drugs were in agreement with the data obtained in vivo. Islet TF could be
      a more predictive in vitro model for routine short- and long-term anti-diabetic
      drug efficacy testing. 

PMID- 23977330
TI  - Recipient's genetic R702W NOD2 variant is associated with an increased risk of
      bacterial infections after orthotopic liver transplantation.
AB  - INTRODUCTION: Orthotopic liver transplantation (OLT) is accompanied by a
      significant postoperative infection risk. Immunosuppression to prevent rejection
      increases the susceptibility to infections, mainly by impairing the adaptive
      immune system. Genetic polymorphisms in the lectin complement pathway of the
      donor have recently been identified as important risk determinants of clinically
      significant bacterial infection (CSI) after OLT. Another genetic factor involved
      in innate immunity is NOD2, which was reported to be associated with increased
      risk of spontaneous bacterial peritonitis in cirrhotic patients. METHODS: We
      assessed association of three genetic NOD2 variants (R702W, G908R and 3020insC)
      with increased risk of CSI after OLT. 288 OLT recipient-donor pairs from two
      tertiary referral centers were genotyped for the three NOD2 variants. The
      probability of CSI in relation to NOD2 gene variants was determined with
      cumulative incidence curves and log-rank analysis. RESULTS: The R702W NOD2
      variant in the recipient was associated with CSI after OLT. Eight out of 15
      (53.3%) individuals with a mutated genotype compared to 80/273 (29.3%) with wild
      type genotype developed CSI (p=0.027, univariate cox regression), illustrated by
      a higher frequency of CSI after OLT over time (p=0.0003, log rank analysis).
      Multivariate analysis (including the donor lectin complement pathway profile)
      showed independence of this R702W NOD2 association from other risk factors (HR
      2.0; p=0.04). The other NOD2 variants, G908R and 3020insC, in the recipient were
      not associated with CSI. There was no association with CSI after OLT for any of
      the NOD2 variants in the donor. CONCLUSION: The mutated NOD2 R702W genotype in
      the recipient is independently associated with an increased risk of bacterial
      infections after liver transplantation, indicating a predisposing role for this
      genetic factor impairing the recipient's innate immune system.

PMID- 23977331
TI  - Seeded fibrillation as molecular basis of the species barrier in human prion
      diseases.
AB  - Prion diseases are transmissible spongiform encephalopathies in humans and
      animals, including scrapie in sheep, bovine spongiform encephalopathy (BSE) in
      cattle, chronic wasting disease (CWD) in deer, and Creutzfeldt-Jakob disease
      (CJD) in humans. The hallmark of prion diseases is the conversion of the host
      encoded prion protein (PrP(C)) to its pathological isoform PrP(Sc), which is
      accompanied by PrP fibrillation. Transmission is not restricted within one
      species, but can also occur between species. In some cases a species barrier can
      be observed that results in limited or unsuccessful transmission. The mechanism
      behind interspecies transmissibility or species barriers is not completely
      understood. To analyse this process at a molecular level, we previously
      established an in vitro fibrillation assay, in which recombinant PrP (recPrP) as
      substrate can be specifically seeded by PrP(Sc) as seed. Seeding with purified
      components, with no additional cellular components, is a direct consequence of
      the "prion-protein-only" hypothesis. We therefore hypothesise, that the species
      barrier is based on the interaction of PrP(C) and PrP(Sc). Whereas in our earlier
      studies, the interspecies transmission in animal systems was analysed, the focus
      of this study lies on the transmission from animals to humans. We therefore
      combined seeds from species cattle, sheep and deer (BSE, scrapie, CWD) with human
      recPrP. Homologous seeding served as a control. Our results are consistent with
      epidemiology, other in vitro aggregation studies, and bioassays investigating the
      transmission between humans, cattle, sheep, and deer. In contrast to CJD and BSE
      seeds, which show a seeding activity we can demonstrate a species barrier for
      seeds from scrapie and CWD in vitro. We could show that the seeding activity and
      therewith the molecular interaction of PrP as substrate and PrP(Sc) as seed is
      sufficient to explain the phenomenon of species barriers. Therefore our data
      supports the hypothesis that CWD is not transmissible to humans. 

PMID- 23977332
TI  - The influence of tobacco smoking on the relationship between pressure and flow in
      the middle cerebral artery in humans.
AB  - BACKGROUND: Cigarette smoking is associated with an increased risk of stroke but
      the mechanism is unclear. The study examined whether acute and chronic cigarette
      smoking alters the dynamic relationship between blood pressure and cerebral blood
      flow. We hypothesised that acute and chronic smoking would result in a cerebral
      circulation that was less capable of buffering against dynamic fluctuations in
      blood pressure. Further, these changes would be accompanied by a reduction in
      baroreflex sensitivity, which is reduced after smoking (acute smoking). METHODS:
      We recruited 17 non-smokers and 15 habitual smokers (13 +/- 5 pack years).
      Continuous measurements of mean cerebral blood flow velocity (transcranial
      Doppler ultrasound), blood pressure (finger photoplethysmography) and heart rate
      enabled transfer function analysis of the dynamic relationship between pressure
      and flow (gain, normalised gain, phase and coherence) and baroreflex sensitivity
      during supine rest before and after smoking a single cigarette (acute smoking).
      RESULTS: There were no between-group differences in gain, phase or coherence
      before acute smoking. However, both groups showed a reduction in gain and
      coherence, associated with a reduction in baroreflex sensitivity, and increase in
      phase after acute smoking. CONCLUSIONS: Contrary to our hypothesis, these
      findings suggest that in the face of a reduction in baroreflex sensitivity acute
      smoking may potentially improve the ability of the cerebral circulation to buffer
      against changes in blood pressure. However, chronic smoking did not alter the
      dynamic relationship between blood pressure and cerebral blood flow velocity.
      These results have implications on understanding mechanisms for attenuating
      stroke risk.

PMID- 23977333
TI  - Inactivation of glucocorticoid receptor in noradrenergic system influences
      anxiety- and depressive-like behavior in mice.
AB  - The aim of this study was to investigate whether conditional inactivation of the
      glucocorticoid receptors (GRs) in noradrenergic neurons affects animal behavior
      in mice. Selective ablation of GRs in the noradrenergic system was achieved using
      the Cre/loxP approach. We crossed transgenic mice expressing the Cre recombinase
      under the dopamine beta-hydroxylase (DBH) promoter with animals harboring the
      floxed GR gene. The resulting GR(DBHCre) mutant mice exhibited no alterations in
      terms of normal cage behavior, weight gain, spatial memory or spontaneous
      locomotor activity, regardless of gender. To assess depressive- and anxiety-like
      behaviors we performed the Tail Suspension Test and the Light-Dark Box Test.
      While male mutant animals did not show any alternations in both tests, female
      GR(DBHCre) mutants displayed depressive- and anxiety-like behavior. Additionally,
      male GR(DBHCre) mice were exposed to chronic restraint stress but still exhibited
      immobility times and anxiety statuses similar to those of non-stressed animals
      while stressed control mice clearly revealed depressive- and anxiety-like
      phenotype. Thus, in males the effects of the mutation were precipitated only
      after chronic restraint stress procedure. Our data reveal a possible gender
      dependent role of GRs in the noradrenergic system in anxiety- and depressive-like
      behavior in mice. 

PMID- 23977334
TI  - Maintenance therapy with immunomodulatory drugs after autologous stem cell
      transplantation in patients with multiple myeloma: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Although high-dose therapy (HDT) with autologous stem cell
      transplantation (ASCT) has been confirmed to result in longer remission time than
      conventional chemotherapy, multiple myeloma (MM) remains incurable. Post-ASCT
      maintenance is considered as a strategy for obtaining durable remissions and
      preventing tumor progression. Randomized controlled trials (RCTs) studying
      maintenance therapy with immunomodulatory drugs (IMiDs) after ASCT have shown
      some valuable survival improvements. This meta-analysis of RCTs therefore
      assesses the effect of post-ASCT IMiDs maintenance on MM patients. METHODS: We
      performed a meta-analysis to evaluate the impact of IMiDs (thalidomide or
      lenalidomide) as post-ASCT maintenance therapy on the survival of newly diagnosed
      MM patients. The outcomes for this meta-analysis were progression-free survival
      (PFS) and overall survival (OS). RESULTS: Eight RCTs enrolling 3514 patients were
      included for analysis. An obvious improvement in Os (hazard ratio [HR] 0.75) and
      a significant PFS advantage (HR 0.58) with post-ASCT IMiDs maintenance was
      revealed. Thalidomide maintenance after ASCT can result in significant benefit in
      Os (HR 0.72), particularly combined with corticosteroids (HR 0.66). CONCLUSIONS:
      MM patients after ASCT have a significant overall survival benefit with IMiDs
      maintenance. IMiDs maintenance was justified for MM patients who received HDT
      with ASCT.

PMID- 23977335
TI  - Neighborhood socioeconomic circumstances and the co-occurrence of unhealthy
      lifestyles: evidence from 206,457 Australians in the 45 and up study.
AB  - BACKGROUND: Research on the co-occurrence of unhealthy lifestyles has tended to
      focus mainly upon the demographic and socioeconomic characteristics of
      individuals. This study investigated the relevance of neighborhood socioeconomic
      circumstance for multiple unhealthy lifestyles. METHOD: An unhealthy lifestyle
      index was constructed for 206,457 participants in the 45 and Up Study (2006-2009)
      by summing binary responses on smoking, alcohol, physical activity and five diet
      related variables. Higher scores indicated the co-occurrence of unhealthy
      lifestyles. Association with self-rated health, quality of life; and risk of
      psychological distress was investigated using multilevel logistic regression.
      Association between the unhealthy lifestyle index with neighborhood
      characteristics (local affluence and geographic remoteness) were assessed using
      multilevel linear regression, adjusting for individual-level characteristics.
      RESULTS: Nearly 50% of the sample reported 3 or 4 unhealthy lifestyles. Only 1.5%
      reported zero unhealthy lifestyles and 0.2% had all eight. Compared to people who
      scored zero, those who scored 8 (the 'unhealthiest' group) were 7 times more
      likely to rate their health as poor (95%CI 3.6, 13.7), 5 times more likely to
      report poor quality of life (95%CI 2.6, 10.1), and had a 2.6 times greater risk
      of psychological distress (95%CI 1.8, 3.7). Higher scores among men decreased
      with age, whereas a parabolic distribution was observed among women. Neighborhood
      affluence was independently associated with lower scores on the unhealthy
      lifestyle index. People on high incomes scored higher on the unhealthy lifestyle
      index if they were in poorer neighborhoods, while those on low incomes had fewer
      unhealthy lifestyles if living in more affluent areas. INTERPRETATION: Residents
      of deprived neighborhoods tend to report more unhealthy lifestyles than their
      peers in affluent areas, regardless of their individual demographic and
      socioeconomic characteristics. Future research should investigate the trade-offs
      of population-level versus geographically targeted multiple lifestyle
      interventions.

PMID- 23977336
TI  - Male weasels decrease activity and energy expenditure in response to high ambient
      temperatures.
AB  - The heat dissipation limit (HDL) hypothesis suggests that the capacity of
      endotherms to dissipate body heat may impose constraints on their energy
      expenditure. Specifically, this hypothesis predicts that endotherms should avoid
      the detrimental consequences of hyperthermia by lowering their energy expenditure
      and reducing their activity in response to high ambient temperatures (T(a)). We
      used an extensive data set on the daily energy expenditure (DEE, n = 27) and the
      daily activity time (AT, n = 48) of male weasels (Mustela nivalis) during the
      spring and summer breeding season to test these predictions. We found that T(a)
      was related in a "hump-shaped" (i.e. convex) manner to AT, DEE, resting metabolic
      rate (RMR) and metabolic scope (the ratio of DEE to RMR). These results support
      the HDL hypothesis because in response to warm Tas male weasels reduced their AT,
      DEE, and RMR. Although the activity and energy expenditure of large endotherms
      are most likely to be constrained in response to warm Tas because they are less
      able to dissipate heat, our results suggest that small endotherms may also
      experience constraints consistent with the HDL hypothesis.

PMID- 23977337
TI  - Analysis of the maternal and child health care status in Suizhou City, Hubei
      Province, China, from 2005 to 2011.
AB  - BACKGROUND: Improving the health and well-being of women and children has long
      been a common goal throughout the world. From 2005 to 2011, Suizhou City had an
      annual average of 22,405 pregnant and parturient women (1.04% of the population)
      and 98,811 children under 5 years old (4.57% of the population). Understanding
      the status of maternal and child health care in Suizhou City during such period
      can provide the local health administrative department valid scientific bases
      upon which to construct effective policies. METHODS: Various types of annual
      reports on maternal and child health care were collected and analyzed
      retrospectively. RESULTS: Mortality rates for infants and children under 5 years
      showed a declining trend, while the rates of newborn home visiting, maternal
      health service coverage, and children health systematic management increased
      annually in Suizhou City from 2005 to 2011. The incidence of birth defect
      increased from 2.42 0/00 in 2005 to 3.89 0/00 in 2011. The maternal mortality
      ratio (MMR) fluctuated from 8.39/100,000 to 28.77/100,000, which was much lower
      than the national MMR (30.0/100,000 in 2010). The rates of hospitalized delivery
      and births attended by trained health personnel for pregnant women increased to
      more than 90% in the past five years. CONCLUSIONS: The improvements in maternal
      and child health care work in Suizhou City are worthy of recognition. Thus, the
      government should continue to increase funding in these areas to promote the
      complete enhancement of the maternal and child health care system.

PMID- 23977338
TI  - Pharmacokinetics and pharmacodynamics of recombinant human EPO-Fc fusion protein
      in vivo.
AB  - In this study, the in vivo pharmacokinetics and pharmacodynamics of a novel
      recombinant human erythropoietin (rhEPO) Fc fusion protein, rhEPO-Fc, were
      studied in both rodents and rhesus monkeys. Animal models of anemia induced by
      irradiation, cyclophosphamide and partial renal ablation were used to evaluate
      therapeutic effects of rhEPO-Fc. We have demonstrated that serum half-life of
      rhEPO-Fc was 29.5 to 38.9 h at doses of 8, 25, 80 ug/kg in rhesus monkeys and
      35.5 to 43.5 h at doses of 16, 50, 160 ug/kg in rats. In anemia animal models,
      rhEPO-Fc dose-dependently (7.5-30.0 ug/kg in mice, 5.4-21.4 ug/kg in rats and 5.0
      10.0 ug/kg in rhesus monkeys) increased reticulocyte level, followed by an
      increase of RBC count, hemoglobin and hematocrit levels. At reduced intervention
      frequency of weekly treatments, rhEPO-Fc showed similar hematopoietic effects as
      compared with rhEPO given three times a week. These results indicated that rhEPO
      Fc could potentially be used in treatment of anemia and warrants future clinical
      trials. 

PMID- 23977340
TI  - Novel ergonomic postural assessment method (NERPA) using product-process computer
      aided engineering for ergonomic workplace design.
AB  - BACKGROUND: Musculoskeletal disorders (MSDs) that result from poor ergonomic
      design are one of the occupational disorders of greatest concern in the
      industrial sector. A key advantage in the primary design phase is to focus on a
      method of assessment that detects and evaluates the potential risks experienced
      by the operative when faced with these types of physical injuries. The method of
      assessment will improve the process design identifying potential ergonomic
      improvements from various design alternatives or activities undertaken as part of
      the cycle of continuous improvement throughout the differing phases of the
      product life cycle. METHODOLOGY/PRINCIPAL FINDINGS: This paper presents a novel
      postural assessment method (NERPA) fit for product-process design, which was
      developed with the help of a digital human model together with a 3D CAD tool,
      which is widely used in the aeronautic and automotive industries. The power of 3D
      visualization and the possibility of studying the actual assembly sequence in a
      virtual environment can allow the functional performance of the parts to be
      addressed. Such tools can also provide us with an ergonomic workstation design,
      together with a competitive advantage in the assembly process. CONCLUSIONS: The
      method developed was used in the design of six production lines, studying 240
      manual assembly operations and improving 21 of them. This study demonstrated the
      proposed method's usefulness and found statistically significant differences in
      the evaluations of the proposed method and the widely used Rapid Upper Limb
      Assessment (RULA) method.

PMID- 23977341
TI  - Replication-independent endogenous DNA double-strand breaks in Saccharomyces
      cerevisiae model.
AB  - Without exposure to any DNA-damaging agents, non-dividing eukaryotic cells carry
      endogenous DNA double-strand breaks (EDSBs), or Replication-Independent (RIND)
      EDSBs. In human cells, RIND-EDSBs are enriched in the methylated heterochromatic
      areas of the genome and are repaired by an ATM-dependent non-homologous end
      joining pathway (NHEJ). Here, we showed that Saccharomyces cerevisiae similarly
      possess RIND-EDSBs. Various levels of EDSBs were detected during different phases
      of the cell cycle, including G0. Using a collection of mutant yeast strains, we
      investigated various DNA metabolic and DNA repair pathways that might be involved
      in the maintenance of RIND-EDSB levels. We found that the RIND-EDSB levels
      increased significantly in yeast strains lacking proteins involved in NHEJ DNA
      repair and in suppression of heterochromatin formation. RIND-EDSB levels were
      also upregulated when genes encoding histone deacetylase, endonucleases,
      topoisomerase, and DNA repair regulators were deleted. In contrast, RIND-EDSB
      levels were downregulated in the mutants that lack chromatin-condensing proteins,
      such as the high-mobility group box proteins, and Sir2. Likewise, RIND-EDSB
      levels were also decreased in human cells lacking HMGB1. Therefore, we conclude
      that the genomic levels of RIND-EDSBs are evolutionally conserved, dynamically
      regulated, and may be influenced by genome topology, chromatin structure, and the
      efficiency of DNA repair systems. 

PMID- 23977339
TI  - In vitro neutralization of low dose inocula at physiological concentrations of a
      monoclonal antibody which protects macaques against SHIV challenge.
AB  - BACKGROUND: Passive transfer of antibodies can be protective in the simian human
      immunodeficiency virus (SHIV)--rhesus macaque challenge model. The human
      monoclonal antibody IgG1 b12 neutralizes human immunodeficiency type 1 (HIV-1) in
      vitro and protects against challenge by SHIV. Our hypothesis is that neutralizing
      antibodies can only completely inactivate a relatively small number of infectious
      virus. METHODS AND FINDINGS: We have used GHOST cell assays to quantify
      individual infectious events with HIV-1SF162 and its SHIV derivatives: the
      relatively neutralization sensitive SHIV(SF162P4) isolate and the more resistant
      SHIV(SF162P3). A plot of the number of fluorescent GHOST cells with increasing
      HIV-1SF162 dose is not linear. It is likely that with high-dose inocula,
      infection with multiple virus produces additive fluorescence in individual cells.
      In studies of the neutralization kinetics of IgG1 b12 against these isolates,
      events during the absorption phase of the assay, as well as the incubation phase,
      determine the level of neutralization. It is possible that complete inactivation
      of a virus is limited to the time it is exposed on the cell surface. Assays can
      be modified so that neutralization of these very low doses of virus can be
      quantified. A higher concentration of antibody is required to neutralize the same
      dose of resistant SHIV(SF162P3) than the sensitive SHIV(SF162P4). In the absence
      of selection during passage, the density of the CCR5 co-receptor on the GHOST
      cell surface is reduced. Changes in the CD4 : CCR5 density ratio influence
      neutralization. CONCLUSIONS: Low concentrations of IgG1 b12 completely inactivate
      small doses of the neutralization resistant SHIV(SF162P3). Assays need to be
      modified to quantify this effect. Results from modified assays may predict
      protection following repeated low-dose shiv challenges in rhesus macaques. It
      should be possible to induce this level of antibody by vaccination so that
      modified assays could predict the outcome of human trials.

PMID- 23977342
TI  - New blocking antibodies impede adhesion, migration and survival of ovarian cancer
      cells, highlighting MFGE8 as a potential therapeutic target of human ovarian
      carcinoma.
AB  - Milk Fat Globule--EGF--factor VIII (MFGE8), also called lactadherin, is a
      secreted protein, which binds extracellularly to phosphatidylserine and to
      alphavbeta3 and alphavbeta5 integrins. On human and mouse cells expressing these
      integrins, such as endothelial cells, phagocytes and some tumors,
      MFGE8/lactadherin has been shown to promote survival, epithelial to mesenchymal
      transition and phagocytosis. A protumoral function of MFGE8 has consequently been
      documented for a few types of human cancers, including melanoma, a subtype of
      breast cancers, and bladder carcinoma. Inhibiting the functions of MFGE8 could
      thus represent a new type of therapy for human cancers. Here, we show by
      immunohistochemistry on a collection of human ovarian cancers that MFGE8 is
      overexpressed in 45% of these tumors, and we confirm that it is specifically
      overexpressed in the triple-negative subtype of human breast cancers. We have
      established new in vitro assays to measure the effect of MFGE8 on survival,
      adhesion and migration of human ovarian and triple-negative breast cancer cell
      lines. Using these assays, we could identify new MFGE8-specific monoclonal
      antibodies, which efficiently blocked these three tumor-promoting effects of
      MFGE8. Our results suggest future use of MFGE8-blocking antibodies as new anti
      cancer therapeutics in subgroups of ovarian carcinoma, and triple-negative breast
      carcinoma patients.

PMID- 23977343
TI  - Interferon-beta produces synergistic combinatory anti-tumor effects with
      cisplatin or pemetrexed on mesothelioma cells.
AB  - Interferons (IFNs) have been tested for the therapeutic effects in various types
      of malignancy, but mechanisms of the anti-tumors effects and the differential
      biological activities among IFN members are dependent on respective cell types.
      In this study, we examined growth inhibitory activities of type I and III IFNs on
      5 kinds of human mesothelioma cells bearing wild-type p53 gene, and showed that
      type I IFNs but not type III IFNs decreased the cell viabilities. Moreover,
      growth inhibitory activities and up-regulated expression levels of the major
      histocompatibility complexes class I antigens were greater with IFN-beta than
      with IFN-alpha treatments. Cell cycle analyses demonstrated that type I IFNs
      increased S- and G2/M-phase populations, and subsequently sub-G1-phase fractions.
      The cell cycle changes were also greater with IFN-beta than IFN-alpha treatments,
      and these data collectively showed that IFN-beta had stronger biological
      activities than IFN-alpha in mesothelioma. Type I IFNs-treated cells increased
      p53 expression and the phosphorylation levels, and activated apoptotic pathways.
      A combinatory use of IFN-beta and cisplatin or pemetrexed, both of which are the
      current first-line chemotherapeutic agents for mesothelioma, produced synergistic
      anti-tumor effects, which were also evidenced by increased sub-G1-phase
      fractions. These data demonstrated firstly to our knowledge that IFN-beta
      produced synergistic anti-tumor effects with cisplatin or pemetrexed on
      mesothelioma through up-regulated p53 expression. 

PMID- 23977344
TI  - Tracking through life stages: adult, immature and juvenile autumn migration in a
      long-lived seabird.
AB  - Seasonal long-distance migration is likely to be experienced in a contrasted
      manner by juvenile, immature and adult birds, leading to variations in migratory
      routes, timing and behaviour. We provide the first analysis of late summer
      movements and autumn migration in these three life stages, which were tracked
      concurrently using satellite tags, geolocators or GPS recorders in a long-ranging
      migratory seabird, the Scopoli's shearwater (formerly named Cory's shearwater,
      Calonectrisdiomedea) breeding on two French Mediterranean islands. During the
      late breeding season, immatures foraged around their colony like breeding adults,
      but they were the only group showing potential prospecting movements around non
      natal colonies. Global migration routes were broadly comparable between the two
      populations and the three life stages, with all individuals heading towards the
      Atlantic Ocean through the strait of Gibraltar and travelling along the West
      African coast, up to 8000 km from their colony. However, detailed comparison of
      timing, trajectory and oceanographic conditions experienced by the birds revealed
      remarkable age-related differences. Compared to adults and immatures, juveniles
      made a longer stop-over in the Balearic Sea (10 days vs 4 days in average),
      showed lower synchrony in crossing the Gibraltar strait, had more sinuous
      pathways and covered longer daily distances (240 km.d(-1) vs 170 km.d(-1)).
      Analysis of oceanographic habitats along migratory routes revealed funnelling
      selection of habitat towards coastal and more productive waters with increasing
      age. Younger birds may have reduced navigational ability and learn progressively
      fine-scale migration routes towards the more profitable travelling and wintering
      areas. Our study demonstrates the importance of tracking long-lived species
      through the stages, to better understand migratory behavior and assess
      differential exposure to at-sea threats. Shared distribution between life stages
      and populations make Scopoli's shearwaters particularly vulnerable to extreme
      mortality events in autumn and winter. Such knowledge is key for the conservation
      of critical marine habitats. 

PMID- 23977345
TI  - Influence of global atmospheric change on the feeding behavior and growth
      performance of a mammalian herbivore, Microtus ochrogaster.
AB  - Global atmospheric change is influencing the quality of plants as a resource for
      herbivores. We investigated the impacts of elevated carbon dioxide (CO2) and
      ozone (O3) on the phytochemistry of two forbs, Solidago canadensis and Taraxacum
      officinale, and the subsequent feeding behavior and growth performance of
      weanling prairie voles (Microtus ochrogaster) feeding on those plants. Plants for
      the chemical analyses and feeding trials were harvested from the understory of
      control (ambient air), elevated CO2 (560 ul CO2 l(-1)), and elevated O3 (ambient
      * 1.5) rings at the Aspen FACE (Free Air CO2 Enrichment) site near Rhinelander,
      Wisconsin. We assigned individual voles to receive plants from only one FACE ring
      and recorded plant consumption and weanling body mass for seven days. Elevated
      CO2 and O3 altered the foliar chemistry of both forbs, but only female weanling
      voles on the O3 diet showed negative responses to these changes. Elevated CO2
      increased the fiber fractions of both plant species, whereas O3 fumigation
      elicited strong responses among many phytochemical components, most notably
      increasing the carbon-to-nitrogen ratio by 40% and decreasing N by 26%.
      Consumption did not differ between plant species or among fumigation treatments.
      Male voles were unaffected by the fumigation treatments, whereas female voles
      grew 36% less than controls when fed O3-grown plants. These results demonstrate
      that global atmospheric change has the potential to affect the performance of a
      mammalian herbivore through changes in plant chemistry. 

PMID- 23977346
TI  - Sensorimotor integration in dyslexic children under different sensory
      stimulations.
AB  - Dyslexic children, besides difficulties in mastering literacy, also show poor
      postural control that might be related to how sensory cues coming from different
      sensory channels are integrated into proper motor activity. Therefore, the aim of
      this study was to examine the relationship between sensory information and body
      sway, with visual and somatosensory information manipulated independent and
      concurrently, in dyslexic children. Thirty dyslexic and 30 non-dyslexic children
      were asked to stand as still as possible inside of a moving room either with eyes
      closed or open and either lightly touching a moveable surface or not for 60
      seconds under five experimental conditions: (1) no vision and no touch; (2)
      moving room; (3) moving bar; (4) moving room and stationary touch; and (5)
      stationary room and moving bar. Body sway magnitude and the relationship between
      room/bar movement and body sway were examined. Results showed that dyslexic
      children swayed more than non-dyslexic children in all sensory condition.
      Moreover, in those trials with conflicting vision and touch manipulation,
      dyslexic children swayed less coherent with the stimulus manipulation compared to
      non-dyslexic children. Finally, dyslexic children showed higher body sway
      variability and applied higher force while touching the bar compared to non
      dyslexic children. Based upon these results, we can suggest that dyslexic
      children are able to use visual and somatosensory information to control their
      posture and use the same underlying neural control processes as non-dyslexic
      children. However, dyslexic children show poorer performance and more variability
      while relating visual and somatosensory information and motor action even during
      a task that does not require an active cognitive and motor involvement. Further,
      in sensory conflict conditions, dyslexic children showed less coherent and more
      variable body sway. These results suggest that dyslexic children have
      difficulties in multisensory integration because they may suffer from integrating
      sensory cues coming from multiple sources. 

PMID- 23977347
TI  - Flower volatiles, crop varieties and bee responses.
AB  - Pollination contributes to an estimated one third of global food production,
      through both the improvement of the yield and the quality of crops. Volatile
      compounds emitted by crop flowers mediate plant-pollinator interactions, but
      differences between crop varieties are still little explored. We investigated
      whether the visitation of crop flowers is determined by variety-specific flower
      volatiles using strawberry varieties (Fragaria x ananassa Duchesne) and how this
      affects the pollination services of the wild bee Osmia bicornis L. Flower
      volatile compounds of three strawberry varieties were measured via headspace
      collection. Gas chromatography showed that the three strawberry varieties
      produced the same volatile compounds but with quantitative differences of the
      total amount of volatiles and between distinct compounds. Electroantennographic
      recordings showed that inexperienced females of Osmia bicornis had higher
      antennal responses to all volatile compounds than to controls of air and paraffin
      oil, however responses differed between compounds. The variety Sonata was found
      to emit a total higher level of volatiles and also higher levels of most of the
      compounds that evoked antennal responses compared with the other varieties
      Honeoye and Darselect. Sonata also received more flower visits from Osmia
      bicornis females under field conditions, compared with Honeoye. Our results
      suggest that differences in the emission of flower volatile compounds among
      strawberry varieties mediate their attractiveness to females of Osmia bicornis.
      Since quality and quantity of marketable fruits depend on optimal pollination, a
      better understanding of the role of flower volatiles in crop production is
      required and should be considered more closely in crop-variety breeding. 

PMID- 23977348
TI  - Polymorphism in the retinoic acid metabolizing enzyme CYP26B1 and the development
      of Crohn's Disease.
AB  - Several studies suggest that Vitamin A may be involved in the pathogenesis of
      inflammatory bowel disease (IBD), but the mechanism is still unknown. Cytochrome
      P450 26 B1 (CYP26B1) is involved in the degradation of retinoic acid and the
      polymorphism rs2241057 has an elevated catabolic function of retinoic acid, why
      we hypothesized that the rs2241057 polymorphism may affect the risk of Crohn's
      disease (CD) and Ulcerative Colitis (UC). DNA from 1378 IBD patients, divided
      into 871 patients with CD and 507 with UC, and 1205 healthy controls collected at
      Orebro University Hospital and Karolinska University Hospital were analyzed for
      the CYP26B1 rs2241057 polymorphism with TaqMan(r) SNP Genotyping Assay followed
      by allelic discrimination analysis. A higher frequency of patients homozygous for
      the major (T) allele was associated with CD but not UC compared to the frequency
      found in healthy controls. A significant association between the major allele and
      non-stricturing, non-penetrating phenotype was evident for CD. However, the
      observed associations reached borderline significance only, after correcting for
      multiple testing. We suggest that homozygous carriers of the major (T) allele,
      relative to homozygous carriers of the minor (C) allele, of the CYP26B1
      polymorphism rs2241057 may have an increased risk for the development of CD,
      which possibly may be due to elevated levels of retinoic acid. Our data may
      support the role of Vitamin A in the pathophysiology of CD, but the exact
      mechanisms remain to be elucidated. 

PMID- 23977350
TI  - Functional roles affect diversity-succession relationships for boreal beetles.
AB  - Species diversity commonly increases with succession and this relationship is an
      important justification for conserving large areas of old-growth habitats.
      However, species with different ecological roles respond differently to
      succession. We examined the relationship between a range of diversity measures
      and time since disturbance for boreal forest beetles collected over a 285 year
      forest chronosequence. We compared responses of "functional" groups related to
      threat status, dependence on dead wood habitats, diet and the type of trap in
      which they were collected (indicative of the breadth of ecologies of species). We
      examined fits of commonly used rank-abundance models for each age class and
      traditional and derived diversity indices. Rank abundance distributions were
      closest to the Zipf-Mandelbrot distribution, suggesting little role for
      competition in structuring most assemblages. Diversity measures for most
      functional groups increased with succession, but differences in slopes were
      common. Evenness declined with succession; more so for red-listed species than
      common species. Saproxylic species increased in diversity with succession while
      non-saproxylic species did not. Slopes for fungivores were steeper than other
      diet groups, while detritivores were not strongly affected by succession. Species
      trapped using emergence traps (log specialists) responded more weakly to
      succession than those trapped using flight intercept traps (representing a
      broader set of ecologies). Species associated with microhabitats that accumulate
      with succession (fungi and dead wood) thus showed the strongest diversity
      responses to succession. These clear differences between functional group
      responses to forest succession should be considered in planning landscapes for
      optimum conservation value, particularly functional resilience. 

PMID- 23977349
TI  - Myo1e impairment results in actin reorganization, podocyte dysfunction, and
      proteinuria in zebrafish and cultured podocytes.
AB  - BACKGROUND: Podocytes serve as an important constituent of the glomerular
      filtration barrier. Recently, we and others identified Myo1e as a key molecular
      component of the podocyte cytoskeleton. RESULTS: Myo1e mRNA and protein was
      expressed in human and mouse kidney sections as determined by Northern blot and
      reverse transcriptase PCR, and its expression was more evident in podocytes by
      immunofluorescence. By specific knock-down of MYO1E in zebrafish, the injected
      larvae exhibited pericardial edema and pronephric cysts, consistent with the
      appearance of protein in condensed incubation supernate. Furthermore, specific
      inhibition of Myo1e expression in a conditionally immortalized podocyte cell line
      induced morphological changes, actin cytoskeleton rearrangement, and dysfunction
      in cell proliferation, migration, endocytosis, and adhesion with the glomerular
      basement membrane. CONCLUSIONS: Our results revealed that Myo1e is a key
      component contributing to the functional integrity of podocytes. Its impairment
      may cause actin cytoskeleton re-organization, alteration of cell shape, and
      membrane transport, and podocyte drop-out from the glomerular basement membrane,
      which might eventually lead to an impaired glomerular filtration barrier and
      proteinuria.

PMID- 23977351
TI  - Capacity of lung stroma to educate dendritic cells inhibiting mycobacteria
      specific T-cell response depends upon genetic susceptibility to tuberculosis.
AB  - The balance between activation and inhibition of local immune responses in
      affected tissues during prolonged chronic infections is important for host
      protection. There is ample evidence that regulatory, tolerogenic dendritic cells
      (DC) are developed and present in tissues and inhibit overwhelming inflammatory
      reactions. Also, it was firmly established that stromal microenvironment of many
      organs is able to induce development of immature regulatory DC (DCreg), an
      essential element of a general immune regulatory network. However, direct
      experimental data demonstrating inhibition of immune responses by stroma
      instructed immature DCreg in infectious models are scarce, and virtually nothing
      is known about functioning of this axis of immunity during tuberculosis (TB)
      infection. In this study, we demonstrate that lung stromal cells are capable of
      supporting the development in culture of immature CD11b(+)CD11c(low)CD103(-)
      DCreg from lineage-negative (lin(-)) bone marrow precursors. DCreg developed on
      lung stroma isolated from mice of genetically TB-hyper-susceptible I/St and
      relatively resistant B6 inbred strains inhibited proliferative response of
      mycobacteria-specific CD4(+) T-cell lines a dose-dependent manner. Importantly,
      the inhibitory activity of B6 DCreg was substantially higher than that of I/St
      Dcreg. Moreover, when the donors of stromal cells were chronically infected with
      virulent mycobacteria, the capacity to instruct inhibitory DCreg was retained in
      B6, but further diminished in I/St stromal cells. DCreg-provided suppression was
      mediated by a few soluble mediators, including PGE2, NO and IL-10. The content of
      CD4(+)Foxp3(+) Treg cells in the mediastinal, lung-draining lymph nodes at the
      advanced stages of chronic infection did not change in I/St, but increased 2-fold
      in B6 mice, and lung pathology was much more pronounced in the former mice. Taken
      together, these data provide genetic evidence that the capacity to maintain
      populations of regulatory cells during M. tuberculosis infection is a part of the
      host protective strategy. 

PMID- 23977352
TI  - Evidence for multiple distinct interactions between hepatitis B virus P protein
      and its cognate RNA encapsidation signal during initiation of reverse
      transcription.
AB  - Replication of hepatitis B virus (HBV) via protein-primed reverse transcription
      is initiated by binding of the viral P protein to the conserved epsilon stem-loop
      on the pregenomic (pg) RNA. This triggers encapsidation of the complex and the
      epsilon-templated synthesis of a short P protein-linked DNA oligonucleotide
      (priming) for subsequent minus-strand DNA extension. epsilon consists of a lower
      and upper stem, a bulge containing the priming template, and an apical loop. The
      nonhelical subelements are considered important for DNA synthesis and pgRNA
      packaging whereas the role of the upper stem is not well characterized. Priming
      itself could until recently not be addressed because in vitro generated HBV P -
      epsilon complexes showed no activity. Focussing on the four A residues at the
      base and tip of the upper epsilon stem and the two U residues in the loop we
      first investigated the impact of 24 mutations on viral DNA accumulation in
      transfected cells. While surprisingly many mutations were tolerated, further
      analyzing the negatively acting mutations, including in a new cell-free priming
      system, revealed divergent position-related impacts on pgRNA packaging, priming
      activity and possibly initiation site selection. This genetic separability
      implies that the epsilon RNA undergoes multiple distinct interactions with P
      protein as pgRNA encapsidation and replication initiation progress, and that the
      strict conservation of epsilon in nature may reflect its optimal adaptation to
      comply with all of them. The data further define the most attractive mutants for
      future studies, including as decoys for interference with HBV replication. 

PMID- 23977353
TI  - Transient gene expression in serum-free suspension-growing mammalian cells for
      the production of foot-and-mouth disease virus empty capsids.
AB  - Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed
      animals. It produces severe economic losses in the livestock industry. Currently
      available vaccines are based on inactivated FMD virus (FMDV). The use of empty
      capsids as a subunit vaccine has been reported to be a promising candidate
      because it avoids the use of virus in the vaccine production and conserves the
      conformational epitopes of the virus. In this report, we explored transient gene
      expression (TGE) in serum-free suspension-growing mammalian cells for the
      production of FMDV recombinant empty capsids as a subunit vaccine. The
      recombinant proteins produced, assembled into empty capsids and induced
      protective immune response against viral challenge in mice. Furthermore, they
      were recognized by anti-FMDV bovine sera. By using this technology, we were able
      to achieve expression levels that are compatible with the development of a
      vaccine. Thus, TGE of mammalian cells is an easy to perform, scalable and cost
      effective technology for the production of a recombinant subunit vaccine against
      FMDV. 

PMID- 23977354
TI  - Complete genome sequence of a Panton-Valentine leukocidin-negative community
      associated methicillin-resistant Staphylococcus aureus strain of sequence type 72
      from Korea.
AB  - In the past decade, community-associated (CA-) infections with methicillin
      resistant Staphylococcus aureus (MRSA) have emerged throughout the world.
      Different CA-MRSA strains dominate in different geographical locations. Many CA
      MRSA lineages contain genes coding for the Panton-Valentine leukocidin. However,
      the role of this leukotoxin in CA-MRSA pathogenesis is still controversial. The
      genome sequences of two key PVL-positive CA-MRSA strains (USA300, USA400) have
      been reported, but we lack information on the more recently found PVL-negative CA
      MRSA strains. One such strain is the PVL-negative ST72, the main cause of CA-MRSA
      infections in Korea. Here, we report the entire genome sequence of CA-MRSA ST72
      and analyze its gene content with a focus on virulence factors. Our results show
      that this strain does not have considerable differences in virulence factor
      content compared to other CA-MRSA strains (USA300, USA400), indicating that other
      toxins do not substitute for the lack of PVL in ST72. This finding is in
      accordance with the notion that differential expression of widespread virulence
      determinants, rather than the acquisition of additional virulence factors on
      mobile genetic elements, such as PVL, is responsible for the increased virulence
      of CA- compared to hospital-associated MRSA. 

PMID- 23977355
TI  - The importance of bushmeat in the livelihoods of West African cash-crop farmers
      living in a faunally-depleted landscape.
AB  - Bushmeat is an important resource in the livelihoods of many rural communities in
      sub-Saharan Africa and may be a crucial safety-net for the most vulnerable
      households, especially during times of economic hardship. However, little is
      known about the impacts of wildlife depletion on these functions. This study
      quantifies the role of bushmeat in diversified rural household economies in a
      wildlife depleted forest-farm landscape in Ghana, assessing its importance
      overall, as well as differentiated by the relative vulnerability of households.
      Using repeat socioeconomic questionnaires (N=787) among 63 households over a one
      year period, the following hypotheses were tested: (a) vulnerable households
      harvest more bushmeat; (b) bushmeat contributes a greater proportion of household
      production in vulnerable households; (c) bushmeat is more important for cash
      income than consumption in vulnerable households; and (d) bushmeat sales are more
      important for vulnerable households. The bushmeat harvest value averaged less
      than US$1.0 per day for 89% of households and comprised less than 7% of household
      production value. Household wealth and gender of the household head had little
      effect on the importance of bushmeat. However, bushmeat harvest and sales were
      highest during the agricultural lean season. Overall, most harvested bushmeat
      (64%) was consumed, enabling households to spend 30% less on meat/fish purchases.
      These findings suggest that, despite heavily depleted wildlife and diversified
      livelihoods, bushmeat continues to have an important role in rural livelihoods by
      acting as a safety net for income smoothing and reducing household expenditure
      during times of economic hardship. 

PMID- 23977356
TI  - Limited TCF7L2 expression in MS lesions.
AB  - Multiple sclerosis is the most frequent demyelinating disease in the human CNS
      characterized by inflammation, demyelination, relative axonal loss and gliosis.
      Remyelination occurs, but is frequently absent or restricted to a small
      remyelinated rim at the lesion border. Impaired differentiation of
      oligodendroglial precursor cells is one factor contributing to limited
      remyelination, especially in chronic MS. TCF7L2 is an oligodendroglial
      transcription factor regulating myelin gene expression during developmental
      myelination as well as remyelination. TCF7L2 binds to co-effectors such as beta
      catenin or histone deacetylases and thereby activates or inhibits the
      transcription of downstream genes involved in oligodendroglial differentiation.
      To determine whether TCF7L2 can be used as a marker for differentiating or
      myelinating oligodendrocytes, we analyzed the expression patterns of TCF7L2
      during myelination and remyelination in human and murine CNS tissue samples.
      Here, we demonstrate that marked expression of TCF7L2 in oligodendrocytes is
      restricted to a well defined time period during developmental myelination in
      human and mouse CNS tissue samples. In demyelinating diseases, such as multiple
      sclerosis, TCF7L2 is reexpressed in oligodendrocytes in a subset of MS patients,
      but is also present in tissue samples from patients with non-demyelinating,
      inflammatory diseases. Furthermore, TCF7L2 expression was also detected in
      astrocytes. HDAC2, a potential binding partner of TCF7L2 that promotes
      oligodendroglial differentiation and myelination, is expressed in the majority of
      oligodendrocytes in controls and MS tissue samples. In summary, our data
      demonstrate that the expression of TCF7L2 in oligodendrocytes is limited to a
      certain differentiation stage; however the expression of TCF7L2 is neither
      restricted to the oligodendroglial lineage nor to (re-)myelinating conditions. 

PMID- 23977358
TI  - Prodromal functioning of migraine patients relative to their interictal state--an
      ecological momentary assessment study.
AB  - Smartphones were used in an online Ecological Momentary Assessment (EMA) design
      to test prodromal functioning relative to the interictal state in migraine
      patients. Eighty-seven participants completed an electronic diary 4 times daily
      during 3-6 weeks to monitor their migraine attacks. Twice daily the diary
      additionally included 16 multi-answer questions covering physical symptoms (30
      items), cognitive-affective functioning (25 items) and external factors (25
      items). Eight clustered prodromal features were identified in the current study:
      sensory sensitivity, pain/stiffness, fatigue, cognitive functioning, positive
      affect, negative affect, effort spent and stressors encountered. Per feature,
      individual change scores with interictal control days--excluding 24-hour post
      attack recovery--were computed for six 12-hour pre-attack time windows covering
      three prodromal days. Linear mixed model (fixed-effect) analysis established
      significant increases in sensory sensitivity, pain/stiffness and fatigue, and a
      tendency for increased negative affect, in the 12 hours prior to the attack.
      Positive affect and cognitive functioning were impaired both in the 25-36 hour
      and--more strongly--in the 12-hour time window before the attack. No effects were
      found for effort spent and stressors encountered. Exploratory (random effect)
      analysis revealed significant individual differences in the change scores in
      sensory sensitivity, pain/stiffness, fatigue and negative affect. It is concluded
      that the prodromal change in migraine--relative to interictal functioning-
      predominantly exists within the last 12 hours before attack onset. Individual
      diversity is large, however. Future research should zoom in to identify prodrome
      development within the 12 pre-attack hours as well as to isolate individual
      patterns.

PMID- 23977357
TI  - HEXIM1 induces differentiation of human pluripotent stem cells.
AB  - Hexamethylene bisacetamide inducible protein 1 (HEXIM1) is best known as the
      inhibitor of positive transcription elongation factor b (P-TEFb), which is
      composed of cyclin-dependent kinase 9 (CDK9)/cyclin T1. P-TEFb is an essential
      regulator for the transcriptional elongation by RNA polymerase II. A genome-wide
      study using human embryonic stem cells shows that most mRNA synthesis is
      regulated at the stage of transcription elongation, suggesting a possible role
      for P-TEFb/HEXIM1 in the gene regulation of stem cells. In this report, we
      detected a marked increase in HEXIM1 protein levels in the differentiated human
      pluripotent stem cells (hPSCs) induced by LY294002 treatment. Since no changes in
      CDK9 and cyclin T1 were observed in the LY294002-treated cells, increased levels
      of HEXIM1 might lead to inhibition of P-TEFb activity. However, treatment with a
      potent P-TEFb inhibiting compound, flavopiridol, failed to induce hPSC
      differentiation, ruling out the possible requirement for P-TEFb kinase activity
      in hPSC differentiation. Conversely, differentiation was observed when hPSCs were
      incubated with hexamethylene bisacetamide, a HEXIM1 inducing reagent. The
      involvement of HEXIM1 in the regulation of hPSCs was further supported when
      overexpression of HEXIM1 concomitantly induced hPSC differentiation.
      Collectively, our study demonstrates a novel role of HEXIM1 in regulating hPSC
      fate through a P-TEFb-independent pathway. 

PMID- 23977360
TI  - The plasma mitochondrial DNA is an independent predictor for post-traumatic
      systemic inflammatory response syndrome.
AB  - BACKGROUND AND PURPOSE: Mitochondrial DNA (mtDNA), a newly identified damage
      associated molecular pattern, has been observed in trauma patients, however,
      little is known concerning the relationship between plasma mtDNA levels and
      concrete post-traumatic complications, particularly systemic inflammatory
      response syndrome (SIRS). The aim of this study is to determine whether plasma
      mtDNA levels are associated with injury severity and cloud predict post-traumatic
      SIRS in patients with acute traumatic injury. PATIENTS AND METHODS: Eighty-six
      consecutive patients with acute traumatic injury were prospectively enrolled in
      this study. The plasma mtDNA concentration was measured by a real-time,
      quantitative PCR assay for the human ND2 gene. The study population's clinical
      and laboratory data were analyzed. RESULTS: The median plasma mtDNA was higher in
      trauma patients than in healthy controls (865.196 (251.042-2565.40)pg/ml vs
      64.2147 (43.9049-80.6371)pg/ml, P<0.001) and was independently correlated with
      the ISS score (r=0.287, P<0.001). The plasma mtDNA concentration was also
      significantly higher in patients who developed post-traumatic SIRS than in
      patients who did not (1774.03 (564.870-10901.3)pg/ml vs 500.496 (145.415
      1285.60)pg/ml, P<0.001). Multiple logistic regression analysis revealed that the
      plasma mtDNA was an independent predictors for post-traumatic SIRS (OR, 1.183
      (95%CI, 1.015-1.379), P=0.032). Further ROC analysis demonstrated that a high
      plasma mtDNA level predicted post-traumatic SIRS with a sensitivity of 67% and a
      specificity of 76%, with a cut-off value of 1.3185 ug/ml being established, and
      the area under the ROC curves (AUC) was 0.725 (95% CI 0.613-0.837). CONCLUSIONS:
      Plasma mtDNA was an independent indictor with moderate discriminative power to
      predict the risk of post-traumatic SIRS.

PMID- 23977359
TI  - IFN-alpha regulates Blimp-1 expression via miR-23a and miR-125b in both monocytes
      derived DC and pDC.
AB  - Type I interferon (IFN-I) have emerged as crucial mediators of cellular signals
      controlling DC differentiation and function. Human DC differentiated from
      monocytes in the presence of IFN-alpha (IFN-alpha DC) show a partially mature
      phenotype and a special capability of stimulating CD4+ T cell and cross-priming
      CD8+ T cells. Likewise, plasmacytoid DC (pDC) are blood DC highly specialized in
      the production of IFN-alpha in response to viruses and other danger signals,
      whose functional features may be shaped by IFN-I. Here, we investigated the
      molecular mechanisms stimulated by IFN-alpha in driving human monocyte-derived DC
      differentiation and performed parallel studies on peripheral unstimulated and IFN
      alpha-treated pDC. A specific miRNA signature was induced in IFN-alpha DC and
      selected miRNAs, among which miR-23a and miR-125b, proved to be negatively
      associated with up-modulation of Blimp-1 occurring during IFN-alpha-driven DC
      differentiation. Of note, monocyte-derived IFN-alpha DC and in vitro IFN-alpha
      treated pDC shared a restricted pattern of miRNAs regulating Blimp-1 expression
      as well as some similar phenotypic, molecular and functional hallmarks,
      supporting the existence of a potential relationship between these DC
      populations. On the whole, these data uncover a new role of Blimp-1 in human DC
      differentiation driven by IFN-alpha and identify Blimp-1 as an IFN-alpha-mediated
      key regulator potentially accounting for shared functional features between IFN
      alpha DC and pDC. 

PMID- 23977362
TI  - Control control control: a reassessment and comparison of GenBank and
      chromatogram mtDNA sequence variation in Baltic grey seals (Halichoerus grypus).
AB  - Genetic data can provide a powerful tool for those interested in the biology,
      management and conservation of wildlife, but also lead to erroneous conclusions
      if appropriate controls are not taken at all steps of the analytical process.
      This particularly applies to data deposited in public repositories such as
      GenBank, whose utility relies heavily on the assumption of high data quality.
      Here we report on an in-depth reassessment and comparison of GenBank and
      chromatogram mtDNA sequence data generated in a previous study of Baltic grey
      seals. By re-editing the original chromatogram data we found that approximately
      40% of the grey seal mtDNA haplotype sequences posted in GenBank contained
      errors. The re-analysis of the edited chromatogram data yielded overall similar
      results and conclusions as the original study. However, a significantly different
      outcome was observed when using the uncorrected dataset based on the GenBank
      haplotypes. We therefore suggest disregarding the existing GenBank data and
      instead using the correct haplotypes reported here. Our study serves as an
      illustrative example reiterating the importance of quality control through every
      step of a research project, from data generation to interpretation and submission
      to an online repository. Errors conducted in any step may lead to biased results
      and conclusions, and could impact management decisions. 

PMID- 23977361
TI  - Head turning-induced hypotension in elderly people.
AB  - Carotid sinus hypersensitivity has a high prevalence in the elderly and is a
      possible cause of falls. In carotid sinus hypersensitivity, external triggers
      cause sudden reductions in blood pressure, leading to dizziness or syncope,
      resulting in falls. Turning of the head is considered an important example of
      such an external trigger in everyday life, wherein rotation of the neck is
      thought to manipulate the hypersensitive carotid sinus. However, direct evidence
      for this is lacking. The aim of this study was to investigate the effects of head
      turning in elderly with carotid sinus hypersensitivity. We performed a
      prospective, observational study in 105 elderly patients who visited a geriatric
      falls clinic in a university teaching hospital and in 25 community dwelling
      healthy elderly subjects. Continuous measurements of blood pressure and heart
      rate (Finapres) were performed before, during, and after head turning. Head
      turning-induced hypotension was defined as a drop in systolic blood pressure of
      at least 20 mmHg during head turning. Carotid sinus hypersensitivity was examined
      with carotid sinus massage. We also tested for two other common geriatric
      hypotensive syndromes, orthostatic hypotension and post prandial hypotension,
      using active standing and a meal test. All three hypotensive syndromes were
      defined using consensus definitions. Head turning resulted in hypotension in 39%
      of patients (mean systolic blood pressure drop 36 mm Hg) and in 44% of the
      healthy elderly, irrespective of the direction of the head movement. Carotid
      sinus hypersensitivity was associated with head-turning induced hypotension (OR=
      3.5, 95% CI= 1.48 to 8.35). We conclude that head turning is indeed an important
      cause of sudden drops in blood pressure in elderly with carotid sinus
      hypersensitivity. 

PMID- 23977363
TI  - alpha-MSH analogue attenuates blood pressure elevation in DOCA-salt hypertensive
      mice.
AB  - Melanocyte-stimulating hormones, alpha-, beta- and gamma-MSH, regulate important
      physiological functions including energy homeostasis, inflammation and sodium
      metabolism. Previous studies have shown that alpha-MSH increases sodium excretion
      and promotes vascular function in rodents, but it is unexplored whether these
      characteristics of alpha-MSH could translate into therapeutic benefits in the
      treatment of hypertension. Therefore, we first assessed the diuretic and
      natriuretic properties of the stable alpha-MSH analogue [Nle(4), D-Phe(7)]-alpha
      MSH (NDP-alpha-MSH) and investigated whether it has protective effects in
      deoxycorticosterone acetate (DOCA)-salt hypertensive mice. Adult male C57Bl/6N
      mice were subjected to DOCA-salt treatment and randomized to receive
      intraperitoneal injections of either saline as vehicle or NDP-alpha-MSH (0.3
      mg/kg/day for 14 days) starting 7 days after the DOCA-salt treatment. Systemic
      hemodynamics, serum and urine electrolytes, and oxidative stress markers were
      assessed in control sham-operated and DOCA-salt mice. NDP-alpha-MSH elicited
      marked diuretic and natriuretic responses that were reversible with the MC3/4
      receptor antagonist SHU9119. Chronic NDP-alpha-MSH treatment attenuated blood
      pressure elevation in DOCA-salt mice without affecting the blood pressure of
      normotensive control animals. Owing to the enhanced sodium excretion, NDP-alpha
      MSH-treated mice were protected from DOCA-salt-induced hypernatremia. DOCA-salt
      treatment mildly increased oxidative stress at the tissue level, but NDP-alpha
      MSH had no significant effects on the oxidative stress markers. In conclusion,
      treatment with NDP-alpha-MSH increases urinary sodium excretion and protects
      against DOCA-salt-induced hypertension. These findings point to the potential
      future use of alpha-MSH analogues in the treatment of hypertension. 

PMID- 23977365
TI  - Use-wear patterns on wild macaque stone tools reveal their behavioural history.
AB  - Burmese long-tailed macaques (Macaca fascicularis aurea) are one of a limited
      number of wild animal species to use stone tools, with their tool use focused on
      pounding shelled marine invertebrates foraged from intertidal habitats. These
      monkeys exhibit two main styles of tool use: axe hammering of oysters, and pound
      hammering of unattached encased foods. In this study, we examined macroscopic use
      wear patterns on a sample of 60 wild macaque stone tools from Piak Nam Yai
      Island, Thailand, that had been collected following behavioural observation, in
      order to (i) quantify the wear patterns in terms of the types and distribution of
      use-damage on the stones, and (ii) develop a Use-Action Index (UAI) to
      differentiate axe hammers from pound hammers by wear patterns alone. We used the
      intensity of crushing damage on differing surface zones of the stones, as well as
      stone weight, to produce a UAI that had 92% concordance when compared to how the
      stones had been used by macaques, as observed independently prior to collection.
      Our study is the first to demonstrate that quantitative archaeological use-wear
      techniques can accurately reconstruct the behavioural histories of non-human
      primate stone tools. 

PMID- 23977364
TI  - Sonic hedgehog carried by microparticles corrects angiotensin II-induced
      hypertension and endothelial dysfunction in mice.
AB  - Microparticles are small fragments of the plasma membrane generated after cell
      stimulation. We recently showed that Sonic hedgehog (Shh) is present in
      microparticles generated from activated/apoptotic human T lymphocytes and
      corrects endothelial injury through nitric oxide (NO) release. This study
      investigates whether microparticles bearing Shh correct angiotensin II-induced
      hypertension and endothelial dysfunction in mice. Male Swiss mice were implanted
      with osmotic minipumps delivering angiotensin II (0.5 mg/kg/day) or NaCl (0.9%).
      Systolic blood pressure and heart rate were measured daily during 21 days. After
      7 day of minipump implantation, mice received i.v. injections of microparticles
      (10 ug/ml) or i.p. Shh receptor antagonist cyclopamine (10 mg/kg/2 days) during
      one week. Angiotensin II induced a significant rise in systolic blood pressure
      without affecting heart rate. Microparticles reversed angiotensin II-induced
      hypertension, and cyclopamine prevented the effects of microparticles.
      Microparticles completely corrected the impairment of acetylcholine- and flow
      induced relaxation in vessels from angiotensin II-infused mice. The improvement
      of endothelial function induced by microparticles was completely prevented by
      cyclopamine treatment. Moreover, microparticles alone did not modify NO and O2 .
      (-) production in aorta, but significantly increased NO and reduced O2. (-)
      productions in aorta from angiotensin II-treated mice, and these effects were
      blocked by cyclopamine. Altogether, these results show that microparticles
      bearing Shh correct angiotensin II-induced hypertension and endothelial
      dysfunction in aorta through a mechanism associated with Shh-induced NO
      production and reduction of oxidative stress. These microparticles may represent
      a new therapeutic approach in cardiovascular diseases associated with decreased
      NO production.

PMID- 23977366
TI  - Epidural analgesia during open radical prostatectomy does not improve long-term
      cancer-related outcome: a retrospective study in patients with advanced prostate
      cancer.
AB  - BACKGROUND: A beneficial effect of regional anesthesia on cancer related outcome
      in various solid tumors has been proposed. The data on prostate cancer is
      conflicting and reports on long-term cancer specific survival are lacking.
      METHODS: In a retrospective, single-center study, outcomes of 148 consecutive
      patients with locally advanced prostate cancer pT3/4 who underwent retropubic
      radical prostatectomy (RRP) with general anesthesia combined with intra- and
      postoperative epidural analgesia (n=67) or with postoperative ketorolac-morphine
      analgesia (n=81) were reviewed. The median observation time was 14.00 years
      (range 10.87-17.75 yrs). Biochemical recurrence (BCR)-free, local and distant
      recurrence-free, cancer-specific, and overall survival were estimated using the
      Kaplan-Meier technique. Multivariate Cox proportional-hazards regression models
      were used to analyze clinicopathologic variables associated with disease
      progression and death. RESULTS: The survival estimates for BCR-free, local and
      distant recurrence-free, cancer-specific survival and overall survival did not
      differ between the two groups (P=0.64, P=0.75, P=0.18, P=0.32 and P=0.07). For
      both groups, higher preoperative PSA (hazard ratio (HR) 1.02, 95% confidence
      interval (CI) 1.01-1.02, P<0.0001), increased specimen Gleason score (HR 1.24,
      95% CI 1.06-1.46, P=0.007) and positive nodal status (HR 1.66, 95% CI 1.03-2.67,
      P=0.04) were associated with higher risk of BCR. Increased specimen Gleason score
      predicted death from prostate cancer (HR 2.46, 95% CI 1.65-3.68, P<0.0001).
      CONCLUSIONS: General anaesthesia combined with epidural analgesia did not reduce
      the risk of cancer progression or improve survival after RRP for prostate cancer
      in this group of patients at high risk for disease progression with a median
      observation time of 14.00 yrs.

PMID- 23977367
TI  - Initial amino acid intake influences phosphorus and calcium homeostasis in
      preterm infants--it is time to change the composition of the early parenteral
      nutrition.
AB  - BACKGROUND: Early aggressive parenteral nutrition (PN), consisting of caloric and
      nitrogen intake soon after birth, is currently proposed for the premature baby.
      Some electrolyte disturbances, such as hypophosphatemia and hypercalcemia,
      considered unusual in early life, were recently described while using this PN
      approach. We hypothesize that, due to its impact on cell metabolism, the initial
      amino acid (AA) amount may specifically influence the metabolism of phosphorus,
      and consequently of calcium. We aim to evaluate the influence of AA intake on
      calcium-phosphorus metabolism, and to create a calculation tool to estimate
      phosphorus needs. METHODS: Prospective observational study. Phosphate and calcium
      plasma concentrations and calcium balance were evaluated daily during the first
      week of life in very preterm infants, and their relationship with nutrition was
      studied. For this purpose, infants were divided into three groups: high, medium
      and low AA intake (HAA, MAA, LAA). A calculation formula to assess phosphorus
      needs was elaborated, with a theoretical model based on AA and calcium intake,
      and the cumulative deficit of phosphate intake was estimated. RESULTS: 154
      infants were included. Hypophosphatemia (12.5%) and hypercalcemia (9.8%) were
      more frequent in the HAA than in the MAA (4.6% and 4.8%) and in the LAA group (0%
      and 1.9%); both p<0.001. DISCUSSION: Calcium-phosphorus homeostasis was
      influenced by the early AA intake. We propose to consider phosphorus and calcium
      imbalances as being part of a syndrome, related to incomplete provision of
      nutrients after the abrupt discontinuation of the placental nutrition at birth
      (PI-ReFeeding syndrome). We provide a simple tool to calculate the optimal
      phosphate intake. The early introduction of AA in the PN soon after birth might
      be completed by an early intake of phosphorus, since AA and phosphorus are (along
      with potassium) the main determinants of cellular growth.

PMID- 23977368
TI  - Diversity of rhizosphere soil arbuscular mycorrhizal fungi in various soybean
      cultivars under different continuous cropping regimes.
AB  - Recent studies have shown that continuous cropping in soybean causes substantial
      changes to the microbial community in rhizosphere soil. In this study, we
      investigated the effects of continuous cropping for various time periods on the
      diversity of rhizosphere soil arbuscular mycorrhizal (AM) fungi in various
      soybean cultivars at the branching stage. The soybean cultivars Heinong 37 (an
      intermediate cultivar), Heinong 44 (a high-fat cultivar) and Heinong 48 (a high
      protein cultivar) were seeded in a field and continuously cropped for two or
      three years. We analyzed the diversity of rhizosphere soil AM fungi of these
      soybean plants at the branching stage using morphological and denaturing gradient
      gel electrophoresis (DGGE) techniques. The clustering analysis of unweighted pair
      group method with arithmetic averages (UPGMA) was then used to investigate the AM
      fungal community shifts. The results showed that increasing the number of years
      of continuous cropping can improve the colonization rate of AM fungi in different
      soybean cultivars at the branching stage. The dominant AM fungi in the
      experimental fields were Funneliformismosseae and Glomus spp. The number of years
      of continuous cropping and the soybean cultivar both had obvious effects on the
      diversity of AM fungi, which was consistent with the results of colonization rate
      analysis. This study establishes a basis for screening dominant AM fungi of
      soybean. In addition, the results of this study may be useful for the development
      of AM fungal inoculants. 

PMID- 23977369
TI  - Effect of reactive oxygen species generation in rabbit corneal epithelial cells
      on inflammatory and apoptotic signaling pathways in the presence of high osmotic
      pressure.
AB  - It is generally accepted that high osmotic pressure (HOP) of lacrimal fluid is
      the core mechanism causing ocular inflammation and injury. However, the
      association between HOP and the regulation of cell inflammatory response and
      apoptotic pathways remains unclear. In the present study, we used HOP to
      interfere with in vitro cultured rabbit corneal epithelial cells, and found that
      HOP increased the generation of reactive oxygen species (ROS) in rabbit corneal
      epithelial cells, and increased ROS in turn induced the activation of JNK
      inflammatory signaling pathway, which further promoted the expression of pro
      inflammatory factor NF-kappabeta and induced the generation of inflammatory
      factor IL-1beta and TNF-alpha. In addition, HOP-induced ROS in rabbit corneal
      epithelial cells regulated the CD95/CD95L-mediated cell apoptotic signaling
      pathway by activating JNK inflammatory signaling pathway. These findings may
      serve as new theoretical basis and a new way of thinking about the treatment of
      ocular diseases, especially dry eye. 

PMID- 23977370
TI  - Electrochemical gating of tricarboxylic acid cycle in electricity-producing
      bacterial cells of Shewanella.
AB  - Energy-conversion systems mediated by bacterial metabolism have recently
      attracted much attention, and therefore, demands for tuning of bacterial
      metabolism are increasing. It is widely recognized that intracellular redox
      atmosphere which is generally tuned by dissolved oxygen concentration or by
      appropriate selection of an electron acceptor for respiration is one of the
      important factors determining the bacterial metabolism. In general,
      electrochemical approaches are valuable for regulation of redox-active objects.
      However, the intracellular redox conditions are extremely difficult to control
      electrochemically because of the presence of insulative phospholipid bilayer
      membranes. In the present work, the limitation can be overcome by use of the
      bacterial genus Shewanella, which consists of species that are able to respire
      via cytochromes abundantly expressed in their outer-membrane with solid-state
      electron acceptors, including anodes. The electrochemical characterization and
      the gene expression analysis revealed that the activity of tricarboxylic acid
      (TCA) cycle in Shewanella cells can be reversibly gated simply by changing the
      anode potential. Importantly, our present results for Shewanella cells cultured
      in an electrochemical system under poised potential conditions showed the
      opposite relationship between the current and electron acceptor energy level, and
      indicate that this unique behavior originates from deactivation of the TCA cycle
      in the (over-)oxidative region. Our result obtained in this study is the first
      demonstration of the electrochemical gating of TCA cycle of living cells. And we
      believe that our findings will contribute to a deeper understanding of redox
      dependent regulation systems in living cells, in which the intracellular redox
      atmosphere is a critical factor determining the regulation of various metabolic
      and genetic processes. 

PMID- 23977371
TI  - Spontaneous bleeding in pancreatitis treated by transcatheter arterial coil
      embolization: a retrospective study.
AB  - BACKGROUND/OBJECTIVES: A rare, but life-threatening complication in pancreatitis
      is a spontaneous bleeding from intestinal vessels with or without previous
      formation of (pseudo-) aneurysms. And yet, the optimal diagnostic and therapeutic
      strategies remain unclear. METHODS: We performed a retrospective analysis of all
      patients with pancreatitis and intraabdominal bleeding at a German tertiary
      referral center between January 2002 and December 2012. RESULTS: Bleeding
      occurred in <1% (14/3,421) of patients with pancreatitis. Most involved vessels
      were arteria lienalis, arteria gastroduodenalis, and arteria
      pancreaticoduodenalis. All bleedings could be stopped by transcatheter arterial
      coil embolization. Recurrent bleeding after coil embolization occurred in 2/14
      (14%) patients. CONCLUSIONS: In cases of intraabdominal hemorrhage in patients
      with pancreatitis, transcatheter arterial coil embolization should be considered
      as the first interventional procedure.

PMID- 23977372
TI  - Myeloid cells expressing VEGF and arginase-1 following uptake of damaged retinal
      pigment epithelium suggests potential mechanism that drives the onset of
      choroidal angiogenesis in mice.
AB  - Whilst data recognise both myeloid cell accumulation during choroidal
      neovascularisation (CNV) as well as complement activation, none of the data has
      presented a clear explanation for the angiogenic drive that promotes pathological
      angiogenesis. One possibility that is a pre-eminent drive is a specific and early
      conditioning and activation of the myeloid cell infiltrate. Using a laser-induced
      CNV murine model, we have identified that disruption of retinal pigment
      epithelium (RPE) and Bruch's membrane resulted in an early recruitment of
      macrophages derived from monocytes and microglia, prior to angiogenesis and
      contemporaneous with lesional complement activation. Early recruited CD11b(+)
      cells expressed a definitive gene signature of selective inflammatory mediators
      particularly a pronounced Arg-1 expression. Accumulating macrophages from retina
      and peripheral blood were activated at the site of injury, displaying enhanced
      VEGF expression, and notably prior to exaggerated VEGF expression from RPE, or
      earliest stages of angiogenesis. All of these initial events, including distinct
      VEGF (+) Arg-1(+) myeloid cells, subsided when CNV was established and at the
      time RPE-VEGF expression was maximal. Depletion of inflammatory CCR2-positive
      monocytes confirmed origin of infiltrating monocyte Arg-1 expression, as
      following depletion Arg-1 signal was lost and CNV suppressed. Furthermore, our in
      vitro data supported a myeloid cell uptake of damaged RPE or its derivatives as a
      mechanism generating VEGF (+) Arg-1(+) phenotype in vivo. Our results reveal a
      potential early driver initiating angiogenesis via myeloid-derived VEGF drive
      following uptake of damaged RPE and deliver an explanation of why CNV develops
      during any of the stages of macular degeneration and can be explored further for
      therapeutic gain. 

PMID- 23977373
TI  - The effect of dexamethasone and triiodothyronine on terminal differentiation of
      primary bovine chondrocytes and chondrogenically differentiated mesenchymal stem
      cells.
AB  - The newly evolved field of regenerative medicine is offering solutions in the
      treatment of bone or cartilage loss and deficiency. Mesenchymal stem cells, as
      well as articular chondrocytes, are potential cells for the generation of bone or
      cartilage. The natural mechanism of bone formation is that of endochondral
      ossification, regulated, among other factors, through the hormones dexamethasone
      and triiodothyronine. We investigated the effects of these hormones on articular
      chondrocytes and chondrogenically differentiated mesenchymal stem cells,
      hypothesizing that these hormones would induce terminal differentiation, with
      chondrocytes and differentiated stem cells being similar in their response. Using
      a 3D-alginate cell culture model, bovine chondrocytes and chondrogenically
      differentiated stem cells were cultured in presence of triiodothyronine or
      dexamethasone, and cell proliferation and extracellular matrix production were
      investigated. Collagen mRNA expression was measured by real-time PCR. Col X mRNA
      and alkaline phosphatase were monitored as markers of terminal differentiation, a
      prerequisite of endochondral ossification. The alginate culture system worked
      well, both for the culture of chondrocytes and for the chondrogenic
      differentiation of mesenchymal stem cells. Dexamethasone led to an increase in
      glycosaminoglycan production. Triiodothyronine increased the total collagen
      production only in chondrocytes, where it also induced signs of terminal
      differentiation, increasing both collagen X mRNA and alkaline phosphatase
      activity. Dexamethasone induced terminal differentiation in the differentiated
      stem cells. The immature articular chondrocytes used in this study seem to be
      able to undergo terminal differentiation, pointing to their possible role in the
      onset of degenerative osteoarthritis, as well as their potential for a cell
      source in bone tissue engineering. When chondrocyte-like cells, after their
      differentiation, can indeed be moved on towards terminal differentiation, they
      can be used to generate a model of endochondral ossification, but this limitation
      must be kept in mind when using them in cartilage tissue engineering application.

PMID- 23977374
TI  - A reinforcing circuit action of extrasynaptic GABAA receptor modulators on
      cerebellar granule cell inhibition.
AB  - GABAA receptors (GABARs) are the targets of a wide variety of modulatory drugs
      which enhance chloride flux through GABAR ion channels. Certain GABAR modulators
      appear to acutely enhance the function of delta subunit-containing GABAR subtypes
      responsible for tonic forms of inhibition. Here we identify a reinforcing circuit
      mechanism by which these drugs, in addition to directly enhancing GABAR function,
      also increase GABA release. Electrophysiological recordings in cerebellar slices
      from rats homozygous for the ethanol-hypersensitive (alpha6100Q) allele show that
      modulators and agonists selective for delta-containing GABARs such as THDOC,
      ethanol and THIP (gaboxadol) increased the frequency of spontaneous inhibitory
      postsynaptic currents (sIPSCs) in granule cells. Ethanol fails to augment granule
      cell sIPSC frequency in the presence of glutamate receptor antagonists,
      indicating that circuit mechanisms involving granule cell output contribute to
      ethanol-enhancement of synaptic inhibition. Additionally, GABAR antagonists
      decrease ethanol-induced enhancement of Golgi cell firing. Consistent with a role
      for glutamatergic inputs, THIP-induced increases in Golgi cell firing are
      abolished by glutamate receptor antagonists. Moreover, THIP enhances the
      frequency of spontaneous excitatory postsynaptic currents in Golgi cells.
      Analyses of knockout mice indicate that delta subunit-containing GABARs are
      required for enhancing GABA release in the presence of ethanol and THIP. The
      limited expression of the GABAR delta subunit protein within the cerebellar
      cortex suggests that an indirect, circuit mechanism is responsible for
      stimulating Golgi cell GABA release by drugs selective for extrasynaptic isoforms
      of GABARs. Such circuit effects reinforce direct actions of these positive
      modulators on tonic GABAergic inhibition and are likely to contribute to the
      potent effect of these compounds as nervous system depressants. 

PMID- 23977375
TI  - Normal CFTR inhibits epidermal growth factor receptor-dependent pro-inflammatory
      chemokine production in human airway epithelial cells.
AB  - Mutations in cystic fibrosis transmembrane conductance regulator (CFTR) protein
      cause cystic fibrosis, a disease characterized by exaggerated airway epithelial
      production of the neutrophil chemokine interleukin (IL)-8, which results in
      exuberant neutrophilic inflammation. Because activation of an epidermal growth
      factor receptor (EGFR) signaling cascade induces airway epithelial IL-8
      production, we hypothesized that normal CFTR suppresses EGFR-dependent IL-8
      production and that loss of CFTR at the surface exaggerates IL-8 production via
      activation of a pro-inflammatory EGFR cascade. We examined this hypothesis in
      human airway epithelial (NCI-H292) cells and in normal human bronchial epithelial
      (NHBE) cells containing normal CFTR treated with a CFTR-selective inhibitor (CFTR
      172), and in human airway epithelial (IB3) cells containing mutant CFTR versus
      isogenic (C38) cells containing wild-type CFTR. In NCI-H292 cells, CFTR-172
      induced IL-8 production EGFR-dependently. Pretreatment with an EGFR neutralizing
      antibody or the metalloprotease TACE inhibitor TAPI-1, or TACE siRNA knockdown
      prevented CFTR-172-induced EGFR phosphorylation (EGFR-P) and IL-8 production,
      implicating TACE-dependent EGFR pro-ligand cleavage in these responses.
      Pretreatment with neutralizing antibodies to IL-1R or to IL-1alpha, but not to IL
      1beta, markedly suppressed CFTR-172-induced EGFR-P and IL-8 production,
      suggesting that binding of IL-1alpha to IL-1R stimulates a TACE-EGFR-IL-8
      cascade. Similarly, in NHBE cells, CFTR-172 increased IL-8 production EGFR-, TACE
      , and IL-1alpha/IL-1R-dependently. In IB3 cells, constitutive IL-8 production was
      markedly increased compared to C38 cells. EGFR-P was increased in IB3 cells
      compared to C38 cells, and exaggerated IL-8 production in the IB3 cells was EGFR
      dependent. Activation of TACE and binding of IL-1alpha to IL-1R contributed to
      EGFR-P and IL-8 production in IB3 cells but not in C38 cells. Thus, we conclude
      that normal CFTR suppresses airway epithelial IL-8 production that occurs via a
      stimulatory EGFR cascade, and that loss of normal CFTR activity exaggerates IL-8
      production via activation of a pro-inflammatory EGFR cascade. 

PMID- 23977376
TI  - Bone marrow and nonbone marrow Toll like receptor 4 regulate acute hepatic injury
      induced by endotoxemia.
AB  - BACKGROUND: Toll-like receptors (TLRs) are expressed in immune cells and
      hepatocytes. We examined whether hepatic Toll-like receptor 4 (TLR4) is involved
      in the acute hepatic injury caused by the administration of lipopolysaccharide
      (LPS) (septic shock model). METHODS: Wild type (WT), TLR4-deficient and chimera
      mice underwent myeloablative bone marrow transplantation to dissociate between
      TLR4 expression in the liver or in the immune-hematopoietic system. Mice were
      injected with LPS and sacrificed 4 hours later. RESULTS: Compared to TLR4
      deficient mice, WT mice challenged with LPS displayed increased serum liver
      enzymes and hepatic cellular inflammatory infiltrate together with increased
      serum and hepatic levels of interleukin 1beta (IL-1beta), tumor necrosis factor
      alpha (TNFalpha) ,Up-regulation of hepatic mRNA encoding TLR4, IkappaB and c-jun
      expressions. TLR4 mutant mice transplanted with WT bone marrow were more
      protected than WT chimeric mice bearing TLR4 mutant hemopoietic cells from LPS,
      as seen by IL-1beta and TNFalpha levels. We then used hepatocytes (Huh7) and
      macrophages from monocytic cell lines to detect TLR mRNA expression. Macrophages
      expressed a significantly higher level of TLR4 mRNA and TLR2 (more than 3000- and
      8000-fold respectively) compared with the hepatocyte cell line. LPS
      administration induced TLR4 activation in a hepatocyte cell line in a dose
      dependent manner while TLR2 mRNA hardly changed. CONCLUSIONS: These results
      suggest that TLR4 activation of hepatocytes participate in the immediate response
      to LPS induced hepatic injury. However, in this response, the contribution of
      TLR4 on bone marrow derived cells is more significant than those of the
      hepatocytes. The absence of the TLR4 gene plays a pivotal role in reducing
      hepatic LPS induced injury.

PMID- 23977377
TI  - Prenatal methyl-donor supplementation augments colitis in young adult mice.
AB  - Inflammatory bowel diseases (IBD) have become highly prevalent in developed
      countries. Environmentally triggered exaggerated immune responses against the
      intestinal microbiome are thought to mediate the disorders. The potential dietary
      origins of the disease group have been implicated. However, the effects of
      environmental influences on prenatal developmental programming in respect to
      orchestrating postnatal microbiome composition and predilection towards mammalian
      colitis have not been examined. We tested how transient prenatal exposure to
      methyl donor micronutrient (MD) supplemented diets may impact predilection
      towards IBD in a murine dextran sulfate sodium (DSS) colitis model. Prenatal MD
      supplementation was sufficient to modulate colonic mucosal Ppara expression (3.2
      fold increase; p=0.022) and worsen DSS colitis in young adulthood. The prenatal
      dietary exposure shifted the postnatal colonic mucosal and cecal content
      microbiomes. Transfer of the gut microbiome from prenatally MD supplemented young
      adult animals into germ free mice resulted in increased colitis susceptibility in
      the recipients compared to controls. Therefore, the prenatal dietary intervention
      induced the postnatal nurturing of a colitogenic microbiome. Our results show
      that prenatal nutritional programming can modulate the mammalian host to harbor a
      colitogenic microbiome. These findings may be relevant for the nutritional
      developmental origins of IBD. 

PMID- 23977378
TI  - Forchlorfenuron disrupts SEPT9_i1 filaments and inhibits HIF-1.
AB  - Forchlorfenuron (FCF) is a synthetic plant cytokinin that has been shown to alter
      yeast and mammalian septin organization. Septins are a highly conserved family of
      GTP-binding cytoskeletal proteins. Mammalian septins are involved in diverse
      cellular processes including tumorigenesis. We have been studying the interaction
      between septin 9 isoform 1 (SEPT9_i1) and hypoxia inducible factor-1alpha (HIF
      1alpha), the oxygen regulated subunit of HIF-1. HIF-1 is a key transcription
      factor in the hypoxic responses pathway, and its activation has been observed in
      carcinogenesis and numerous cancers. SEPT9_i1/HIF-1alpha interaction plays an
      important role in upregulation of HIF-1 transcriptional activity by preventing
      HIF-1alpha's ubiquitination and degradation leading to increased tumor growth and
      angiogenesis. We tested the hypothesis whether FCF affects SEPT9_i1 filamentous
      structures and consequently HIF-1 pathway in cancer cells. We showed that FCF
      suppresses tumorigenic properties, including proliferation, migration and
      transformation, in prostate cancer cells. FCF did not alter SEPT9_i1 steady state
      protein expression levels but it affected its filamentous structures and
      subcellular localization. FCF induced degradation of HIF-1alpha protein in a dose
      and time-dependent manner. This inhibition was also shown in other common cancer
      types tested. Rapid degradation of HIF-1alpha protein levels was accompanied by
      respective inhibition in HIF-1alpha transcriptional activity. Moreover, HIF
      1alpha protein half-life was markedly decreased in the presence of FCF compared
      with that in the absence of FCF. The FCF-induced degradation of HIF-1alpha was
      mediated in a significant part via the proteasome. To the best of our knowledge,
      this is the first demonstration of specific manipulation of septin filaments by
      pharmacological means having downstream inhibitory effects on the HIF-1 pathway. 

PMID- 23977379
TI  - Transcription factor sigmaB plays an important role in the production of
      extracellular membrane-derived vesicles in Listeria monocytogenes.
AB  - Gram-negative bacteria produce extracellular outer membrane vesicles (OMVs) that
      interact with host cells. Unlike Gram-negative bacteria, less is known about the
      production and role of extracellular membrane vesicles (MVs) in Gram-positive
      bacteria. The food-borne pathogen Listeria monocytogenes can survive under
      extreme environmental and energy stress conditions and the transcription factor
      sigma(B) is involved in this survival ability. Here, we first determined the
      production of MVs from L. monocytogenes and evaluated whether general stress
      transcription factor sigma(B) affected production of MVs in L. monocytogenes. L.
      monocytogenes secreted MVs during in vitro broth culture. The wild-type strain
      actively produced MVs approximately nine times more and also produced more intact
      shapes of MVs than those of the isogenic DeltasigB mutant. A proteomic analysis
      showed that 130 and 89 MV proteins were identified in the wild-type and DeltasigB
      mutant strains, respectively. Wild-type strain-derived MVs contained proteins
      regulated by sigma(B) such as transporters (OpuCA and OpuCC), stress response
      (Kat), metabolism (LacD), translation (InfC), and cell division protein (FtsZ).
      Gene Ontology (GO) enrichment analysis showed that wild-type-derived MV proteins
      corresponded to several GO terms, including response to stress (heat, acid, and
      bile resistance) and extracellular polysaccharide biosynthetic process, but not
      the DeltasigB mutant. Internalin B (InlB) was almost three times more contained
      in MVs derived from the wild-type strain than in MVs derived from the DeltasigB
      mutant. Taken together, these results suggest that sigma(B) plays a pivotal role
      in the production of MVs and protein profiles contained in MVs. L. monocytogenes
      MVs may contribute to host infection and survival ability under various stressful
      conditions. 

PMID- 23977380
TI  - Opposite effect of mast cell stabilizers ketotifen and tranilast on the
      vasoconstrictor response to electrical field stimulation in rat mesenteric
      artery.
AB  - OBJECTIVES: We analyzed whether mast cell stabilization by either ketotifen or
      tranilast could alter either sympathetic or nitrergic innervation function in rat
      mesenteric arteries. METHODS: Electrical field stimulation (EFS)-induced
      contraction was analyzed in mesenteric segments from 6-month-old Wistar rats in
      three experimental groups: control, 3-hour ketotifen incubated (0.1 alphamol/L),
      and 3-hour tranilast incubated (0.1 mmol/L). To assess the possible participation
      of nitrergic or sympathetic innervation, EFS contraction was analyzed in the
      presence of non-selective nitric oxide synthase (NOS) inhibitor L-NAME (0.1
      mmol/L), alpha-adrenergic receptor antagonist phentolamine (0.1 umol/L), or the
      neurotoxin 6-hydroxydopamine (6-OHDA, 1.46 mmol/L). Nitric oxide (NO) and
      superoxide anion (O2.(-) levels were measured, as were vasomotor responses to
      noradrenaline (NA) and to NO donor DEA-NO, in the presence and absence of 0.1
      mmol/L tempol. Phosphorylated neuronal NOS (P-nNOS) expression was also analyzed.
      RESULTS: EFS-induced contraction was increased by ketotifen and decreased by
      tranilast. L-NAME increased the vasoconstrictor response to EFS only in control
      segments. The vasodilator response to DEA-NO was higher in ketotifen- and
      tranilast-incubated segments, while tempol increased vasodilator response to DEA
      NO only in control segments. Both NO and O2(-) release, and P-nNOS expression
      were diminished by ketotifen and by tranilast treatment. The decrease in EFS
      induced contraction produced by phentolamine was lower in tranilast-incubated
      segments. NA vasomotor response was decreased only by tranilast. The remnant
      vasoconstriction observed in control and ketotifen-incubated segments was
      abolished by 6-OHDA. CONCLUSION: While both ketotifen and tranilast diminish
      nitrergic innervation function, only tranilast diminishes sympathetic
      innnervation function, thus they alter the vasoconstrictor response to EFS in
      opposing manners.

PMID- 23977381
TI  - Ratio of metastatic to examined lymph nodes, a helpful staging system and
      independent prognostic factor of esophagogastric junction cancer.
AB  - BACKGROUND: The incidence of the esophagogastric junction cancer is growing
      rapidly. The purpose of this study is to clarify the outcome of the ratio between
      metastatic and examined lymph nodes in esophagogastric junction cancer patients
      with or without 7 examined lymph nodes. METHODS: A total of 3,481 patients who
      underwent operation are identified from the Surveillance, Epidemiology, and End
      Results database. Different lymph nodes resected groups are analyzed to test the
      lymph nodes ratio factor. RESULTS: There are 2522 patients with 7 or more lymph
      nodes resected and 959 patients with less than 7 lymph nodes resected. Lymph
      nodes ratio and lymph node involvement are independent prognostic factors. But
      the lymph nodes ratio categories have a better prognostic value than the lymph
      node involvement categories. Compared with lymph node involvement categories,
      lymph nodes ratio categories represent patients with more homogeneous overall
      survival rate. CONCLUSIONS: This study defines that the lymph nodes ratio is an
      independent prognostic factor for esophagogastric junction cancer. The lymph
      nodes ratio can prevent stage migration and may be a helpful system to predict
      the prognosis of esophagogastric junction cancer patients.

PMID- 23977382
TI  - Theta burst stimulation applied over primary motor and somatosensory cortices
      produces analgesia unrelated to the changes in nociceptive event-related
      potentials.
AB  - Continuous theta burst stimulation (cTBS) applied over the primary motor cortex
      (M1) can alleviate pain although the neural basis of this effect remains largely
      unknown. Besides, the primary somatosensory cortex (S1) is thought to play a
      pivotal role in the sensori-discriminative aspects of pain perception but the
      analgesic effect of cTBS applied over S1 remains controversial. To investigate
      cTBS-induced analgesia we characterized, in two separate experiments, the effect
      of cTBS applied either over M1 or S1 on the event-related brain potentials (ERPs)
      and perception elicited by nociceptive (CO2 laser stimulation) and non
      nociceptive (transcutaneous electrical stimulation) somatosensory stimuli. All
      stimuli were delivered to the ipsilateral and contralateral hand. We found that
      both cTBS applied over M1 and cTBS applied over S1 significantly reduced the
      percept elicited by nociceptive stimuli delivered to the contralateral hand as
      compared to similar stimulation of the ipsilateral hand. In contrast, cTBS did
      not modulate the perception of non-nociceptive stimuli. Surprisingly, this side
      dependent analgesic effect of cTBS was not reflected in the amplitude modulation
      of nociceptive ERPs. Indeed, both nociceptive (N160, N240 and P360 waves) and
      late-latency non-nociceptive (N140 and P200 waves) ERPs elicited by stimulation
      of the contralateral and ipsilateral hands were similarly reduced after cTBS,
      suggesting an unspecific effect, possibly due to habituation or reduced
      alertness. In conclusion, cTBS applied over M1 and S1 reduces similarly the
      perception of nociceptive inputs originating from the contralateral hand, but
      this analgesic effect is not reflected in the magnitude of nociceptive ERPs. 

PMID- 23977383
TI  - A new functional role for mechanistic/mammalian target of rapamycin complex 1
      (mTORC1) in the circadian regulation of L-type voltage-gated calcium channels in
      avian cone photoreceptors.
AB  - In the retina, the L-type voltage-gated calcium channels (L-VGCCs) are
      responsible for neurotransmitter release from photoreceptors and are under
      circadian regulation. Both the current densities and protein expression of L
      VGCCs are significantly higher at night than during the day. However, the
      underlying mechanisms of circadian regulation of L-VGCCs in the retina are not
      completely understood. In this study, we demonstrated that the
      mechanistic/mammalian target of rapamycin complex (mTORC) signaling pathway
      participated in the circadian phase-dependent modulation of L-VGCCs. The
      activities of the mTOR cascade, from mTORC1 to its downstream targets, displayed
      circadian oscillations throughout the course of a day. Disruption of mTORC1
      signaling dampened the L-VGCC current densities, as well as the protein
      expression of L-VGCCs at night. The decrease of L-VGCCs at night by mTORC1
      inhibition was in part due to a reduction of L-VGCCalpha1 subunit translocation
      from the cytosol to the plasma membrane. Finally, we showed that mTORC1 was
      downstream of the phosphatidylionositol 3 kinase-protein kinase B (PI3K-AKT)
      signaling pathway. Taken together, mTORC1 signaling played a role in the
      circadian regulation of L-VGCCs, in part through regulation of ion channel
      trafficking and translocation, which brings to light a new functional role for
      mTORC1: the modulation of ion channel activities. 

PMID- 23977384
TI  - Interacting virus abundance and transmission intensity underlie tomato spotted
      wilt virus incidence: an example weather-based model for cultivated tobacco.
AB  - Through a modeling approach, we investigated weather factors that affect the
      summer incidence of Tomato spotted wilt virus (TSWV), a virus vectored
      exclusively by thrips, in cultivated tobacco. Aspects of thrips and plant biology
      that affect disease spread were treated as functions of weather, leading to a
      model of disease incidence informed by thrips and plant biology, and dependent on
      weather input variables. We found that disease incidence during the summer was
      influenced by weather affecting thrips activity during the preceding year,
      especially during a time when thrips transmit TSWV to and from the plant hosts
      that constitute the virus' natural reservoir. We identified an interaction
      between spring precipitation and earlier weather affecting thrips, relating this
      to virus abundance and transmission intensity as interacting factors affecting
      disease incidence. Throughout, weather is the basic driver of epidemiology in the
      system, and our findings allowed us to detect associations between atypically
      high- or low-incidence years and the local climatic deviations from normal
      weather patterns, brought about by El Nino Southern Oscillation transitions. 

PMID- 23977385
TI  - Cell density- and quorum sensing-dependent expression of type VI secretion system
      2 in Vibrio parahaemolyticus.
AB  - BACKGROUND: Vibrio parahaemolyticus AphA and OpaR are the two master quorum
      sensing (QS) regulators that are abundantly expressed at low cell density (LCD)
      and high cell density (HCD), respectively, with a feature of reciprocally
      gradient production of them with transition between LCD and HCD. The type VI
      secretion system 2 (T6SS2) gene cluster can be assigned into three putative
      operons, namely VPA1027-1024, VPA1043-1028, and VPA1044-1046. T6SS2 contributes
      to adhesion of V. parahaemolyticus to host cells. METHODOLOGY/PRINCIPAL FINDINGS:
      OpaR box-like sequences were found within the upstream promoter regions of all
      the above three operons, while none of AphA box-like elements could be identified
      for them. The subsequent primer extension, LacZ fusion, electrophoretic mobility
      shift, and DNase I footprinting assays disclosed that OpaR bound to the promoter
      regions of these three operons to stimulate their transcription, while AphA
      negatively regulated their transcription most likely through acting on OpaR. This
      regulation led to a gradient increase of T6SS2 transcription with transition from
      LCD to HCD. CONCLUSIONS/SIGNIFICANCE: V. parahaemolyticus OpaR and AphA
      positively and negatively regulate T6SS2 expression, respectively, leading to a
      gradient elevation of T6SS2 expression with transition from LCD to HCD. T6SS2
      genes are thus assigned as the QS regulon members in V. parahaemolyticus.

PMID- 23977386
TI  - Evidence for shared cognitive processing of pitch in music and language.
AB  - Language and music epitomize the complex representational and computational
      capacities of the human mind. Strikingly similar in their structural and
      expressive features, a longstanding question is whether the perceptual and
      cognitive mechanisms underlying these abilities are shared or distinct--either
      from each other or from other mental processes. One prominent feature shared
      between language and music is signal encoding using pitch, conveying pragmatics
      and semantics in language and melody in music. We investigated how pitch
      processing is shared between language and music by measuring consistency in
      individual differences in pitch perception across language, music, and three
      control conditions intended to assess basic sensory and domain-general cognitive
      processes. Individuals' pitch perception abilities in language and music were
      most strongly related, even after accounting for performance in all control
      conditions. These results provide behavioral evidence, based on patterns of
      individual differences, that is consistent with the hypothesis that cognitive
      mechanisms for pitch processing may be shared between language and music.

PMID- 23977387
TI  - TRPP2 and TRPV4 form an EGF-activated calcium permeable channel at the apical
      membrane of renal collecting duct cells.
AB  - OBJECTIVE: Regulation of apical calcium entry is important for the function of
      principal cells of the collecting duct. However, the molecular identity and the
      regulators of the transporter/channel, which is responsible for apical calcium
      entry and what factors regulate the calcium conduction remain unclear. METHODS
      AND RESULTS: We report that endogenous TRPP2 and TRPV4 assemble to form a 23-pS
      divalent cation-permeable non-selective ion channel at the apical membrane of
      renal principal cells of the collecting duct. TRPP2?TRPV4 channel complex was
      identified by patch-clamp, immunofluorescence and co-immunprecipitation studies
      in both principal cells that either possess normal cilia (cilia (+)) or in which
      cilia are absent (cilia (-)). This channel has distinct biophysical and
      pharmacological and regulatory profiles compared to either TRPP2 or TRPV4
      channels. The rate of occurrence detected by patch clamp was higher in cilia (-)
      compared to cilia (+) cells. In addition, shRNA knockdown of TRPP2 increased the
      prevalence of TRPV4 channel activity while knockdown of TRPV4 resulted in TRPP2
      activity and knockdown of both proteins vastly decreased the 23-pS channel
      activity. Epidermal growth factor (EGF) stimulated TRPP2?TRPV4 channel through
      the EGF receptor (EGFR) tyrosine kinase-dependent signaling. With loss of cilia,
      apical EGF treatment resulted in 64-fold increase in channel activity in cilia (
      ) but not cilia (+) cells. In addition EGF increased cell proliferation in cilia
      (-) cell that was dependent upon TRPP2?TRPV4 channel mediated increase in
      intracellular calcium. CONCLUSION: We conclude that in the absence of cilia, an
      EGF activated TRPP2?TRPV4 channel may play an important role in increased cell
      proliferation and cystogenesis.

PMID- 23977388
TI  - Life satisfaction and risk of chronic diseases in the European prospective
      investigation into cancer and nutrition (EPIC)-Germany study.
AB  - OBJECTIVE: The aim of the study was to examine the prospective association
      between life satisfaction and risk of type 2 diabetes mellitus, myocardial
      infarction, stroke, and cancer. Previous studies suggested that psychosocial
      factors may affect the development of chronic diseases but the impact of positive
      attitudes, in particular life satisfaction, is yet to be determined. METHODS: The
      analysis included 50,358 participants of the European Prospective Investigation
      into Cancer and Nutrition (EPIC)-Germany study in Potsdam and Heidelberg. Life
      satisfaction was assessed in a baseline interview and incident cases of chronic
      diseases were identified and verified during follow-up. Hazard ratios were
      calculated using Cox proportional hazards regression models that were
      systematically multivariable-adjusted for established risk factors and prevalent
      diseases. RESULTS: During an average of 8 years of follow-up 2,293 cases of
      cancer, 1,840 cases of type 2 diabetes mellitus, 440 cases of stroke, and 562
      cases of myocardial infarction were observed. Women who were unsatisfied with
      life at baseline showed in all models a significantly increased risk of cancer
      (HR: 1.45; 95% CI: 1.18-1.78) and stroke (HR: 1.69; 95% CI: 1.05-2.73) as well as
      an increased risk of type 2 diabetes mellitus by trend across categories (p
      trend=0.04) compared to women very satisfied with life. In men, a relationship
      between life satisfaction and stroke was found but did not persist after
      consideration of lifestyle factors and prevalent diseases. No significant
      association was observed between life satisfaction and risk of myocardial
      infarction. CONCLUSIONS: The results of this study suggest that reduced life
      satisfaction is related to the development of chronic diseases--particularly in
      women and partly mediated by established risk factors.

PMID- 23977389
TI  - Gene-specific DNA methylation association with serum levels of C-reactive protein
      in African Americans.
AB  - A more thorough understanding of the differences in DNA methylation (DNAm)
      profiles in populations may hold promise for identifying molecular mechanisms
      through which genetic and environmental factors jointly contribute to human
      diseases. Inflammation is a key molecular mechanism underlying several chronic
      diseases including cardiovascular disease, and it affects DNAm profile on both
      global and locus-specific levels. To understand the impact of inflammation on the
      DNAm of the human genome, we investigated DNAm profiles of peripheral blood
      leukocytes from 966 African American participants in the Genetic Epidemiology
      Network of Arteriopathy (GENOA) study. By testing the association of DNAm sites
      on CpG islands of over 14,000 genes with C-reactive protein (CRP), an
      inflammatory biomarker of cardiovascular disease, we identified 257 DNAm sites in
      240 genes significantly associated with serum levels of CRP adjusted for age,
      sex, body mass index and smoking status, and corrected for multiple testing. Of
      the significantly associated DNAm sites, 80.5% were hypomethylated with higher
      CRP levels. The most significant Gene Ontology terms enriched in the genes
      associated with the CRP levels were immune system process, immune response,
      defense response, response to stimulus, and response to stress, which are all
      linked to the functions of leukocytes. While the CRP-associated DNAm may be cell
      type specific, understanding the DNAm association with CRP in peripheral blood
      leukocytes of multi-ethnic populations can assist in unveiling the molecular
      mechanism of how the process of inflammation affects the risks of developing
      common disease through epigenetic modifications. 

PMID- 23977390
TI  - Prevalence of PALB2 mutations in breast cancer patients in multi-ethnic Asian
      population in Malaysia and Singapore.
AB  - BACKGROUND: The partner and localizer of breast cancer 2 (PALB2) is responsible
      for facilitating BRCA2-mediated DNA repair by serving as a bridging molecule,
      acting as the physical and functional link between the breast cancer 1 (BRCA1)
      and breast cancer 2 (BRCA2) proteins. Truncating mutations in the PALB2 gene are
      rare but are thought to be associated with increased risks of developing breast
      cancer in various populations. METHODS: We evaluated the contribution of PALB2
      germline mutations in 122 Asian women with breast cancer, all of whom had
      significant family history of breast and other cancers. Further screening for
      nine PALB2 mutations was conducted in 874 Malaysian and 532 Singaporean breast
      cancer patients, and in 1342 unaffected Malaysian and 541 unaffected Singaporean
      women. RESULTS: By analyzing the entire coding region of PALB2, we found two
      novel truncating mutations and ten missense mutations in families tested negative
      for BRCA1/2-mutations. One additional novel truncating PALB2 mutation was
      identified in one patient through genotyping analysis. Our results indicate a low
      prevalence of deleterious PALB2 mutations and a specific mutation profile within
      the Malaysian and Singaporean populations.

PMID- 23977391
TI  - Human APOBEC3A isoforms translocate to the nucleus and induce DNA double strand
      breaks leading to cell stress and death.
AB  - Human APOBEC3 enzymes deaminate single stranded DNA. At least five can deaminate
      mitochondrial DNA in the cytoplasm, while three can deaminate viral DNA in the
      nucleus. However, only one, APOBEC3A, can hypermutate genomic DNA. We analysed
      the distribution and function of the two APOBEC3A isoforms p1 and p2 in
      transfected cell lines. Both can translocate to the nucleus and hypermutate CMYC
      DNA and induce DNA double strand breaks as visualized by the detection of (c)H2AX
      or Chk2. APOBEC3A induced G1 phase cell cycle arrest and triggered several
      members of the intrinsic apoptosis pathway. Activation of purified human CD4+ T
      lymphocytes with PHA, IL2 and interferon alpha resulted in C->T hypermutation of
      genomic DNA and double stranded breaks suggesting a role for APOBEC3A in pro
      inflammatory conditions. As chronic inflammation underlies many diseases
      including numerous cancers, it is possible that APOBEC3A induction may generate
      many of the lesions typical of a cancer genome. 

PMID- 23977392
TI  - Increased Plin2 expression in human skeletal muscle is associated with sarcopenia
      and muscle weakness.
AB  - Human aging is associated with a progressive loss of muscle mass and strength and
      a concomitant fat accumulation in form of inter-muscular adipose tissue, causing
      skeletal muscle function decline and immobilization. Fat accumulation can also
      occur as intra-muscular triglycerides (IMTG) deposition in lipid droplets, which
      are associated with perilipin proteins, such as Perilipin2 (Plin2). It is not
      known whether Plin2 expression changes with age and if this has consequences on
      muscle mass and strength. We studied the expression of Plin2 in the vastus
      lateralis (VL) muscle of both healthy subjects and patients affected by lower
      limb mobility limitation of different age. We found that Plin2 expression
      increases with age, this phenomenon being particularly evident in patients.
      Moreover, Plin2 expression is inversely correlated with quadriceps strength and
      VL thickness. To investigate the molecular mechanisms underpinning this
      phenomenon, we focused on IGF-1/p53 network/signalling pathway, involved in
      muscle physiology. We found that Plin2 expression strongly correlates with
      increased p53 activation and reduced IGF-1 expression. To confirm these
      observations made on humans, we studied mice overexpressing muscle-specific IGF
      1, which are protected from sarcopenia. These mice resulted almost negative for
      the expression of Plin2 and p53 at two years of age. We conclude that fat
      deposition within skeletal muscle in form of Plin2-coated lipid droplets
      increases with age and is associated with decreased muscle strength and
      thickness, likely through an IGF-1- and p53-dependent mechanism. The data also
      suggest that excessive intramuscular fat accumulation could be the initial
      trigger for p53 activation and consequent loss of muscle mass and strength. 

PMID- 23977393
TI  - Disruption of microRNA biogenesis confers resistance to ER stress-induced cell
      death upstream of the mitochondrion.
AB  - Global downregulation of microRNAs (miRNAs) is a common feature of human tumors
      and has been shown to enhance cancer progression. Several components of the miRNA
      biogenesis machinery (XPO5, DICER and TRBP) have been shown to act as
      haploinsufficient tumor suppressors. How the deregulation of miRNA biogenesis
      promotes tumor development is not clearly understood. Here we show that loss of
      miRNA biogenesis increased resistance to endoplasmic reticulum (ER) stress
      induced cell death. We observed that HCT116 cells with a DICER hypomorphic
      mutation (Exn5/Exn5) or where DICER or DROSHA were knocked down were resistant to
      ER stress-induced cell death. Extensive analysis revealed little difference in
      the unfolded protein response (UPR) of WT compared to Exn5/Exn5 HCT116 cells upon
      ER stress treatment. However, analysis of the intrinsic apoptotic pathway showed
      that resistance occurred upstream of the mitochondria. In particular, BAX
      activation and dissipation of mitochondrial membrane potential was attenuated,
      and there was altered expression of BCL-2 family proteins. These observations
      demonstrate a key role for miRNAs as critical modulators of the ER stress
      response. In our model, downregulation of miRNA biogenesis delays ER stress
      induced apoptosis. This suggests that disrupted miRNA biogenesis may contribute
      to cancer progression by inhibiting ER stress-induced cell death. 

PMID- 23977394
TI  - Gene expression network analysis of ETV1 reveals KCTD10 as a novel prognostic
      biomarker in gastrointestinal stromal tumor.
AB  - BACKGROUND: Prognostic biomarkers are required for risk stratification therapy in
      the patients with gastrointestinal stromal tumor (GIST). In this study, we aimed
      to identify prognostic biomarkers in GIST. We assessed the prognostic value of E
      twenty-six variant 1 (ETV1), a recently identified transcription factor unique to
      GIST. We also examined the clinical utility and functions of its downstream gene,
      potassium channel tetramerization domain containing protein 10 (KCTD10). METHODS:
      The levels of ETV1 and KCTD10 were evaluated immunohistochemically in 112
      patients with GIST treated at two hospitals. The functional properties of KCTD10
      were examined by gene silencing assay in cultured GIST cells. RESULTS:
      Immunohistochemistry revealed that ETV1 expression in GIST had no prognostic
      significance. In contrast, the disease-free survival rate was 88.5% in patients
      with KCTD10-positive tumors and 55.8% in those with KCTD10-negative tumors (p
      <0.0001). KCTD10 was an independent prognostic factor (p <0.05). In the low-risk
      classification group, KCTD10 was significantly associated with favorable
      prognosis (p = 0.0008). Gene silencing of KCTD10 increased cell proliferation and
      invasion, suggesting that KCTD10 has a tumor-suppressive function. CONCLUSIONS:
      The GIST-specific transcription factor ETV1 may have no prognostic potential,
      whereas its downstream gene KCTD10 is associated with a favorable prognosis. Our
      study indicated the novel prognostic utility of KCTD10 in GIST, and suggested its
      tumor-suppressive effects on GIST cells. Further validation studies of KCTD10 for
      clinical applications, and functional verification of KCTD10 for better
      understanding of molecular basis of malignant phenotypes are worth challenging in
      GIST.

PMID- 23977395
TI  - Elevation in sphingomyelin synthase activity is associated with increases in
      amyloid-beta peptide generation.
AB  - A pathological hallmark of Alzheimer's disease (AD) is the presence of amyloid
      beta peptide (Abeta) plaques in the brain. Abeta is derived from a sequential
      proteolysis of the transmenbrane amyloid precursor protein (APP), a process which
      is dependent on the distribution of lipids present in the plasma membrane.
      Sphingomyelin is a major membrane lipid, however its role in APP processing is
      unclear. Here, we assessed the expression of sphingomyelin synthase (SGMS1; the
      gene responsible for sphingomyelin synthesis) in human brain and found that it
      was significantly elevated in the hippocampus of AD brains, but not in the
      cerebellum. Secondly, we assessed the impact of altering SGMS activity on Abeta
      generation. Inhibition of SGMS activity significantly reduced the level of Abeta
      in a dose- and time dependent manner. The decrease in Abeta level occurred
      without changes in APP expression or cell viability. These results when put
      together indicate that SGMS activity impacts on APP processing to produce Abeta
      and it could be a contributing factor in Abeta pathology associated with AD. 

PMID- 23977396
TI  - Ablation of RIC8A function in mouse neurons leads to a severe neuromuscular
      phenotype and postnatal death.
AB  - Resistance to inhibitors of cholinesterase 8 (RIC8) is a guanine nucleotide
      exchange factor required for the intracellular regulation of G protein
      signalling. RIC8 activates different Galpha subunits via non-canonical pathway,
      thereby amplifying and prolonging the G protein mediated signal. In order to
      circumvent the embryonic lethality associated with the absence of RIC8A and to
      study its role in the nervous system, we constructed Ric8a conditional knockout
      mice using Cre/loxP technology. Introduction of a synapsin I promoter driven Cre
      transgenic mouse strain (SynCre) into the floxed Ric8a (Ric8a (F/F) ) background
      ablated RIC8A function in most differentiated neuron populations. Mutant SynCre
      (+/-) Ric8 (lacZ/F) mice were born at expected Mendelian ratio, but they died in
      early postnatal age (P4-P6). The mutants exhibited major developmental defects,
      like growth retardation and muscular weakness, impaired coordination and balance,
      muscular spasms and abnormal heart beat. Histological analysis revealed that the
      deficiency of RIC8A in neurons caused skeletal muscle atrophy and heart muscle
      hypoplasia, in addition, the sinoatrial node was misplaced and its size reduced.
      However, we did not observe gross morphological changes in brains of SynCre (+/-)
      Ric8a (lacZ/F) mutants. Our results demonstrate that in mice the activity of
      RIC8A in neurons is essential for survival and its deficiency causes a severe
      neuromuscular phenotype. 

PMID- 23977397
TI  - Amino acids and mTOR mediate distinct metabolic checkpoints in mammalian G1 cell
      cycle.
AB  - OBJECTIVE: In multicellular organisms, cell division is regulated by growth
      factors (GFs). In the absence of GFs, cells exit the cell cycle at a site in G1
      referred to as the restriction point (R) and enter a state of quiescence known as
      G0. Additionally, nutrient availability impacts on G1 cell cycle progression.
      While there is a vast literature on G1 cell cycle progression, confusion remains 
      especially with regard to the temporal location of R relative to nutrient
      mediated checkpoints. In this report, we have investigated the relationship
      between R and a series of metabolic cell cycle checkpoints that regulate passage
      into S-phase. METHODS: We used double-block experiments to order G1 checkpoints
      that monitor the presence of GFs, essential amino acids (EEAs), the conditionally
      essential amino acid glutamine, and inhibition of mTOR. Cell cycle progression
      was monitored by uptake of [(3)H]-thymidine and flow cytometry, and analysis of
      cell cycle regulatory proteins was by Western-blot. RESULTS: We report here that
      the GF-mediated R can be temporally distinguished from a series of late G1
      metabolic checkpoints mediated by EAAs, glutamine, and mTOR - the
      mammalian/mechanistic target of rapamycin. R is clearly upstream from an EAA
      checkpoint, which is upstream from a glutamine checkpoint. mTOR is downstream
      from both the amino acid checkpoints, close to S-phase. Significantly, in
      addition to GF autonomy, we find human cancer cells also have dysregulated
      metabolic checkpoints. CONCLUSION: The data provided here are consistent with a
      GF-dependent mid-G1 R where cells determine whether it is appropriate to divide,
      followed by a series of late-G1 metabolic checkpoints mediated by amino acids and
      mTOR where cells determine whether they have sufficient nutrients to accomplish
      the task. Since mTOR inhibition arrests cells the latest in G1, it is likely the
      final arbiter for nutrient sufficiency prior to committing to replicating the
      genome.

PMID- 23977398
TI  - PKC activation in Niemann pick C1 cells restores subcellular cholesterol
      transport.
AB  - Activation of protein kinase C (PKC) has previously been shown to ameliorate the
      cholesterol transport defect in Niemann Pick Type C1 (NPC1) cells, presumably by
      increasing the soluble levels of one of its substrates, vimentin. This activity
      would then restore the vimentin cycle in these cells and allow vimentin-dependent
      retrograde transport to proceed. Here, we further investigate the effects of PKC
      activation in NPC1 cells by evaluating different isoforms for their ability to
      solubilize vimentin and correct the NPC1 cholesterol storage phenotype. We also
      examine the effects of PKC activators, including free fatty acids and the PKC
      specific activator diazoxide, on the NPC1 disease phenotype. Our results indicate
      that PKC isoforms alpha, betaII, and epsilon have the greatest effects on
      vimentin solubilization. Furthermore, expression or activation of PKCepsilon in
      NPC1 cells dramatically reduces the amount of stored cholesterol and restores
      cholesterol transport out of endocytic vesicles. These results provide further
      support for the contribution of PKCs in NPC1 disease pathogenesis and suggest
      that PKCs may be targeted in future efforts to develop therapeutics for NPC1
      disease. 

PMID- 23977399
TI  - Dynamical observation on biological progression of VX2 liver tumors to identify
      the optimal time for intervention in animal models.
AB  - PURPOSE: Based on practice guideline of "management of hepatocellular carcinoma
      (HCC): update" published by American Association for the Study of Liver Diseases
      (AASLD) and "Barcelona Clinic Liver Cancer staging system (BCLC)," this study
      investigated how to enroll the optimal VX2 liver tumor model for HCC researches
      by dynamically observing the biological progression of the tumor. MATERIALS:
      Thirty-two healthy New Zealand white rabbits were implanted VX2 liver tumor by
      cell suspension method (n=24) and tissue fragment method (n=8). All the rabbits
      underwent CT scans on day 7, 14, 21 and 28 after implantation to observe the size
      of the tumors, the time when metastases and ascites occurred and the survival
      time. Appropriate intervention times were estimated corresponding to different
      clinical HCC stages by using tumor diameter-time curve. RESULTS: The VX2 liver
      tumors grew rapidly within 28 days after implantation. And the tumors in the cell
      suspension group grew faster than those of the tissue fragment group. The
      appropriate intervention time corresponding to very early stage, early stage and
      intermediate stage were <11 days, 11-16.9 days and >16.9 days, respectively in
      the cell suspension group, and <19.9 days, 19.9-25.5 days and >25.5 days,
      respectively in the tissue fragment group. CONCLUSION: Preclinical animal
      research needs to improve on different levels to yield best predictions for human
      patients. Researchers should seek for an individualized proposal to select
      optimal VX2 liver tumor models for their experiments. This approach may lead to a
      more accurate determination of therapeutic outcomes.

PMID- 23977400
TI  - A Val85Met mutation in melanocortin-1 receptor is associated with reductions in
      eumelanic pigmentation and cell surface expression in domestic rock pigeons
      (Columba livia).
AB  - Variation in the melanocortin-1 receptor (Mc1r) is associated with pigmentation
      diversity in wild and domesticated populations of vertebrates, including several
      species of birds. Among domestic bird species, pigmentation variation in the rock
      pigeon (Columbalivia) is particularly diverse. To determine the potential
      contribution of Mc1r variants to pigment diversity in pigeons, we sequenced Mc1r
      in a wide range of pigeon breeds and identified several single nucleotide
      polymorphisms, including a variant that codes for an amino acid substitution
      (Val85Met). In contrast to the association between Val85Met and eumelanism in
      other avian species, this change was associated with pheomelanism in pigeons. In
      vitro cAMP accumulation and protein expression assays revealed that Val85Met
      leads to decreased receptor function and reduced cell surface expression of the
      mutant protein. The reduced in vitro function is consistent with the observed
      association with reduced eumelanic pigmentation. Comparative genetic and cellular
      studies provide important insights about the range of mechanisms underlying
      diversity among vertebrates, including different phenotypic associations with
      similar mutations in different species. 

PMID- 23977401
TI  - Targeted mutagenesis in the malaria mosquito using TALE nucleases.
AB  - Anopheles gambiae, the main mosquito vector of human malaria, is a challenging
      organism to manipulate genetically. As a consequence, reverse genetics studies in
      this disease vector have been largely limited to RNA interference experiments.
      Here, we report the targeted disruption of the immunity gene TEP1 using
      transgenic expression of Transcription-Activator Like Effector Nucleases
      (TALENs), and the isolation of several TEP1 mutant A. gambiae lines. These
      mutations inhibited protein production and rendered TEP1 mutants hypersusceptible
      to Plasmodium berghei. The TALEN technology opens up new avenues for genetic
      analysis in this disease vector and may offer novel biotechnology-based
      approaches for malaria control. 

PMID- 23977402
TI  - Assessing the Location of Surface Plasmons Over Nanotriangle and Nanohole Arrays
      of Different Size and Periodicity.
AB  - The increasing popularity of surface plasmon resonance (SPR) and surface enhanced
      Raman scattering (SERS) sensor design based on nanotriangle or nanohole arrays,
      and the possibility to manufacture substrates at the transition between these
      plasmonic substrates, makes them ideal candidates for the establishment of
      structure-property relationships. This work features near diffraction-limited
      Raman images and FDTD simulations of nanotriangle and nanohole arrays substrates,
      which clearly demonstrate that the localization of the hot spot on these SERS
      substrates is significantly influenced by the ratio of diameter/periodicity
      (D/P). The experimental and simulation data reveal that the hot spots are located
      around nanotriangles (D/P = 1), characteristic of localized SPR. Decreasing the
      D/P ratio to 0.75-0.7 led to the creation of nanohole arrays, which promoted the
      excitation of a propagating surface plasmon (SP) delocalized over the metal
      network. The optimal SERS intensity was consistently achieved at this transition
      from nanotriangles to nanoholes, for every periodicity (650 nm to 1.5 MUm) and
      excitation wavelength (633 and 785 nm) investigated, despite the presence or
      absence of a plasmonic band near the laser excitation. Further decreasing the D/P
      ratio led to excitation of a localized SP located around the rim of nanohole
      arrays for D/P of 0.5-0.6, in agreement with previous reports. In addition, this
      manuscript provides the first evidence that the hot spots are positioned inside
      the hole for D/P of 0.4, with the center being the region of highest electric
      field and Raman intensity. The compelling experimental evidence and FDTD
      simulations offer an overall understanding of the plasmonic properties of
      nanohole arrays as SERS and SPR sensors, which is of significant value in
      advancing the diversity of applications from such surfaces.

PMID- 23977403
TI  - Gold Nanostars For Surface-Enhanced Raman Scattering: Synthesis, Characterization
      and Optimization.
AB  - The controlled synthesis of high-yield gold nanostars of varying sizes, their
      characterization and use in surface-enhanced Raman scattering (SERS) measurements
      are reported for the first time. Gold nanostars ranging from 45 to 116-nm in size
      were synthesized in high-yield, physically modeled and optically characterized
      using transmission and scanning electron microscopy and UV-Visible absorption
      spectroscopy. The nanostar characterization involved both studying morphology
      evolution over time and size as a function of nucleation. The nanostars
      properties as substrates for SERS were investigated and compared with respect to
      size. As the overall star size increases, so does the core size, the number of
      branches and branch aspect ratio; the number of branch tips per star surface area
      decreases with increasing size. The stars become more inhomogeneous in shape,
      although their yield is high and overall size remains homogeneous. Variations in
      star size are also accompanied by shifts of the long plasmon band in the NIR
      region, which hints towards tuning capabilities that may be exploited in specific
      SERS applications. The measured SERS enhancement factors suggest an interesting
      correlation between nanostar size and SERS efficiencies, and were relatively
      consistent across different star samples, with the enhancement factor estimated
      as 5*103 averaged over the 52-nm nanostars for 633-nm excitation.

PMID- 23977404
TI  - Spectral bounds on plasmon resonances for Ag and Au prolate and oblate
      nanospheroids.
AB  - Analytical expressions for the plasmon resonance frequencies of prolate and
      oblate spheroids and their dependence on ellipticity have been derived, and
      approximate bounds on these frequencies established. These formulas may be useful
      in tuning the plasmon resonance within certain limits. With increasing aspect
      ratio, the prolate spheroid resonance is red shifted relative to a sphere with no
      lower limit under the assumptions of a Drude dispersion model. On the other hand,
      the oblate resonances are blue shifted as the spheroid becomes increasingly flat,
      but up to a limit.

PMID- 23977405
TI  - A new perspective on developmental language problems: Perceptual organization
      deficits.
AB  - Children with a variety of language-related problems, including dyslexia,
      experience difficulty processing the acoustic speech signal, leading to proposals
      of diagnostic entities known as auditory processing deficits. Although
      descriptions of these deficits vary across accounts, most hinge on the idea that
      problems arise at the level of detecting and/or discriminating sensory inputs.
      This article re-examines that idea, and proposes that the difficulty more likely
      arises in how those sensations get organized into service for auditory
      comprehension of language.

PMID- 23977406
TI  - Lymphatic mapping could not be impaired in the presence of breast carcinoma and
      coexisting small lymphocytic lymphoma.
AB  - PATIENT: Female, 66 FINAL DIAGNOSIS: Infiltrating ductal carcinoma * small
      lymphocytic lymphoma SYMPTOMS: - MEDICATION: - Clinical Procedure: Sentinel Lymph
      Node Biopsy * lumpectomy * axillary lymph node dissection Specialty: Breast
      cancer surgery. OBJECTIVE: Rare presentation of two concomitant malingancies.
      BACKGROUND: Lymphatic mapping of axillary breast cancer metastases in the
      presence of concomitant lymphoproliferative disease is still a controversial
      topic. Previous reports have postulated that tumor collision in the lymph nodes
      could lead to false-negative results of sentinel lymph node biopsy, leading to
      erroneous staging. CASE REPORT: We present the case of a 66-year-old woman with
      infiltrating ductal breast carcinoma and small lymphocytic lymphoma in whom we
      performed a lumpectomy and sentinel lymph node biopsy with Technetium-99 and 1%
      methylene blue, followed by axillary lymph node dissection regardless of the
      intraoperative status, which was negative. Final pathology confirmed the absence
      of lymph node metastases. CONCLUSIONS: Previously published cases reported
      correct assessment of SLNB in patients with concomitant small lymphocytic
      lymphoma and breast carcinoma. We postulate a possible pathological explanation
      for this: lymphoid cell clusters with pseudofollicles or proliferative centers of
      small lymphocytic lymphoma are localized outside the nodal sinuses of the lymph
      node, maintaining its capability of draining, and thus, the feasibility of SLNB
      in these patients, as in the presented case.

PMID- 23977407
TI  - The role of IL-27 in the induction of anti-tumor cytotoxic T lymphocyte response.
AB  - Cytotoxic T lymphocyte (CTL) response is a critical component of the immune
      response to tumors, therefore optimal induction of CTL responses to tumor
      antigens is highly desired for developing efficient cancer immunotherapy. IL-27
      is a member of the IL-12 family of cytokines that is comprised of an IL-12 p40
      related protein subunit, EBV-induced gene 3 (EBI3), and a p35-related subunit,
      p28. IL-27 functions through IL-27R and has been shown to have potent anti-tumor
      activity via activation of a variety of immune components, including anti-tumor
      CD8(+) T cell responses. However, the exact mechanisms of how IL-27 enhances anti
      tumor CD8(+) T cell responses are not fully understood. In this paper we mainly
      discuss the evidences that suggest novel mechanisms by which IL-27 enhances anti
      tumor CTL responses, including IL-27 inhibition of activation-induced cell death;
      the phenotypes of IL-27-stimulated CTLs; IL-27-induced CTL IL-10/IL-21 production
      and IL-27-mediated suppression of regulatory T cell responses. These evidences
      suggest that IL-27 may have a great potential to be utilized in boosting anti
      tumor CTL responses in human cancer patients. 

PMID- 23977408
TI  - Elevated neutrophil gelatinase-associated lipocalin contributes to erlotinib
      resistance in non-small cell lung cancer.
AB  - PURPOSE: The EGFR tyrosine kinase inhibitors (TKIs) demonstrate efficacy in NSCLC
      patients whose tumors harbor activating EGFR mutations. However, patients who
      initially respond to EGFR TKI treatment invariably develop resistance to the
      drugs. Known mechanisms account for approximately 70% of native and acquired EGFR
      TKI resistance. In the current study we investigated a novel mechanism of NSCLC
      resistance to erlotinib. EXPERIMENTAL DESIGN: The mechanisms of acquired
      erlotinib resistance were evaluated by microarray analysis in thirteen NSCLC cell
      lines and in vivo in mice. Correlations between plasma neutrophil gelatinase
      associated lipocalin (NGAL) levels, erlotinib response and the EGFR mutational
      status were assessed in advanced stage NSCLC patients treated with erlotinib.
      RESULTS: In 5 of 13 NSCLC cell lines NGAL was significantly upregulated. NGAL
      knockdown in erlotinib-resistant cells increased erlotinib sensitivity in vitro
      and in vivo. NGAL overexpression in erlotinib-sensitive cells augmented apoptosis
      resistance. This was mediated by NGAL-dependent modulation of the pro-apoptotic
      protein Bim levels. Evaluation of the plasma NGAL levels in NSCLC patients that
      received erlotinib revealed that patients with lower baseline NGAL demonstrated a
      better erlotinib response. Compared to patients with wild type EGFR, patients
      with activating EGFR mutations had lower plasma NGAL at baseline and weeks 4 and
      8. CONCLUSIONS: Our studies uncover a novel mechanism of NGAL-mediated modulation
      of Bim levels in NSCLC that might contribute to TKI resistance in lung cancer
      patients. These findings provide the rationale for the further investigations of
      the utility of NGAL as a potential therapeutic target or diagnostic biomarker.

PMID- 23977409
TI  - Regular cigarette smoking influences the transsulfuration pathway, endothelial
      function, and inflammation biomarkers in a sex-gender specific manner in healthy
      young humans.
AB  - Cigarette smoking (CS) is the primary cause of preventable morbidity and
      mortality. Abundant clinical evidence suggests that CS is more harmful to women;
      however, the mechanisms responsible for these differences are not yet known. CS
      alters endothelial function, the redox state, inflammation, and global DNA
      methylation, which is associated with one-carbon metabolism and the
      transsulfuration pathway. However, it is not known whether the previously
      identified alterations are sex-gender related. Healthy adult men and oral
      contraceptive-free women with regular menstrual cycles were enrolled; women were
      examined during the follicular phase. Men had higher plasma levels of uric acid,
      total bilirubin, homocysteine, glutamylcysteine, total glutathione,
      cysteinylglycine; had more monocytes and released more TNF-alpha from human
      monocytes derived macrophages (hMDMs), but they had fewer platelets and lower
      levels of DNA methylation, and their hMDMs released less TNF-alpha after LPS
      stimulation. MDA, taurine, cysteine, arginine, ADMA, and SDMA were not different.
      CS decreased global DNA methylation more in women and increased the platelet,
      monocyte, and lymphocyte counts and the homocysteine, arginine, and ADMA levels
      only in women, whereas increased the neutrophil and eosinophil counts only in
      men. Additionally, CS reduced the sex-gender differences in total bilirubin,
      basal and LPS-induced TNF-alpha release, total glutathione, and glutamylcysteine,
      leaving unchanged cysteinylglycine, taurine, SDMA, MDA, and cysteine. These data
      suggest that cardiovascular risk factors seem to come earlier in young healthy
      female smokers than in young healthy male smokers, supporting the greater
      alarmism regarding the effects of CS in women and providing a basis for
      understanding the sex-gender differences. These results also suggest that
      cessation programs targeting women are needed. 

PMID- 23977410
TI  - Chemotaxis of human induced pluripotent stem cell-derived endothelial cells.
AB  - This study examined the homing capacity of human induced pluripotent stem cell
      derived endothelial cells (iPSC-ECs) and their response to chemotactic gradients
      of stromal derived factor-1alpha (SDF). We have previously shown that EC derived
      from murine pluripotent stem cells can home to the ischemic hindlimb of the
      mouse. In the current study, we were interested to understand if ECs derived from
      human induced pluripotent stem cells are capable of homing. The homing capacity
      of iPSC-ECs was assessed after systemic delivery into immunodeficient mice with
      unilateral hindlimb ischemia. Furthermore, the iPSC-ECs were evaluated for their
      expression of CXCR4 and their ability to respond to SDF chemotactic gradients in
      vitro. Upon systemic delivery, the iPSC-ECs transiently localized to the lungs
      but did not home to the ischemic limb over the course of 14 days. To understand
      the mechanism of the lack of homing, the expression levels of the homing
      receptor, CXCR4, was examined at the transcriptional and protein levels.
      Furthermore, their ability to migrate in response to chemokines was assessed
      using microfluidic and scratch assays. Unlike ECs derived from syngeneic mouse
      pluripotent stem cells, human iPSC-ECs do not home to the ischemic mouse
      hindlimb. This lack of functional homing may represent an impairment of
      interspecies cellular communication or a difference in the differentiation state
      of the human iPSC-ECs. These results may have important implications in
      therapeutic delivery of iPSC-ECs. 

PMID- 23977411
TI  - A simplified two-stitch sleeve technique for arterial anastomosis of cervical
      heterotopic cardiac transplantation in mice.
AB  - Although cervical cardiac transplantation is a well recognized useful model in
      diverse experimental settings, its widespread use, however, has been
      significantly hampered by the technical challenges relevant to small vessel
      anastomosis. We herein introduced a simplified two-stitch sleeve technique into
      arterial anastomosis during the course of cervical cardiac transplantation in
      mice. Cervical transplantation of allogenic and syngeneic cardiac grafts was
      conducted to assess the feasibility of this two-stitch sleeve technique in
      arterial anastomosis. Venous anastomosis was completed by the one-suture end-to
      end microsuture technique, while arterial anastomosis was conducted by
      invaginating the recipient right common carotid artery into the graft left common
      carotid artery along with two guiding stitches. The two-stitch sleeve technique
      significantly simplified the procedures for arterial anastomosis as compared with
      that of the traditional microsuture technique (5.5 +/- 1.8 min vs. 15.7 +/- 3.0
      min). However, the survival time for allografts (8.0 +/- 0.2 day vs. 8.0 +/- 0.4
      day) and the long-term patency for syngeneic grafts (> 120 days) were the same as
      the grafts implanted by the traditional microsuture technique. This simplified
      sleeve technique is easy to learn, particularly for beginners without microsuture
      experience, and therefore, it has the great potential for widespread use in
      transplant immunology. 

PMID- 23977412
TI  - Regulation of Monocyte Chemotactic Protein-1 secretion by the Two-Pore-Domain
      Potassium (K2P) channel TREK-1 in human alveolar epithelial cells.
AB  - We recently proposed a role for the 2-pore-domain K(+) (K2P) channel TREK-1 in
      the regulation of cytokine release from alveolar epithelial cells (AECs) by
      demonstrating decreased IL-6 secretion from TREK-1 deficient cells, but the
      effects of altered TREK-1 expression on other inflammatory mediators remain
      poorly understood. We now examined the role of TREK-1 in TNF-alpha-induced MCP-1
      release from human A549 cells. We hypothesized that TREK-1 regulates TNF-alpha
      induced MCP-1 secretion via c-Jun N-terminal kinases (JNK)- and protein kinase-C
      (PKC)-dependent pathways. In contrast to IL-6 secretion, we found that TREK-1
      deficiency resulted in increased MCP-1 production and secretion, although
      baseline MCP-1 gene expression was unchanged in TREK-1 deficient cells. In
      contrast to TREK-1 deficient AECs, overexpression of MCP-1 had no effect on MCP-1
      secretion. Phosphorylation of JNK1/2/3 was increased in TREK-1 deficient cells
      upon TNF-alpha stimulation, but pharmacological inhibition of JNK1/2/3 decreased
      MCP-1 release from both control and TREK-1 deficient cells. Similarly,
      pharmacological inhibition of PKC decreased MCP-1 secretion from control and TREK
      1 deficient cells, suggesting that alterations in JNK and PKC signaling pathways
      were unlikely the cause for the increased MCP-1 secretion from TREK-1 deficient
      cells. Furthermore, MCP-1 secretion from control and TREK-1 deficient cells was
      independent of extracellular Ca(2+) but sensitive to inhibition of intracellular
      Ca(2+) reuptake mechanisms. In summary, we report for the first time that TREK-1
      deficiency in human AECs resulted in increased MCP-1 production and secretion,
      and this effect appeared unrelated to alterations in JNK-, PKC- or Ca(2+)
      mediated signaling pathways in TREK-1 deficient cells. 

PMID- 23977413
TI  - Malnutrition induces gut atrophy and increases hepatic fat infiltration: studies
      in a pig model of childhood malnutrition.
AB  - Childhood malnutrition is a problem in developing countries, and pathological
      changes in digestive organs such as the intestine and liver are poorly
      understood. An animal model to study the progression of severe acute malnutrition
      could elucidate pathological changes in the intestine and liver. We sought to
      characterize growth and clinical changes during malnutrition related to
      structural and functional indices in the intestine and liver. Newly weaned
      piglets were given ad libitum access to a maize flour diet (MAIZE, n=9) or a
      nutritionally optimized reference diet (REFERENCE, n=12) for 7 weeks. Growth,
      hematology and clinical biochemistry where recorded weekly. After 7 weeks, the
      MAIZE pigs had lower body weights than the REF pigs (8.3 kg vs. 32.4 kg, P <
      0.001), indicating severe stunting and moderate to severe wasting. This was
      paralleled by lower values for hematocrit, hemoglobin and mean cell volume in
      MAIZE vs. REFERENCE (P < 0.01), indicating anemia. Although the observed temporal
      changes in MAIZE were associated with atrophy of the small intestinal mucosa (P <
      0.001), digestive enzyme activity was only marginally reduced. Serum alanine
      aminotransferase, bilirubin and albumin were increased in the MAIZE pigs (P <
      0.001), and the liver had a vacuolated appearance and tendency toward increased
      triglyceride content (P=0.054). We conclude that liver and intestinal indices are
      compromised during malnutrition and are associated with temporal changes in
      growth and hematological and biochemical endpoints. The pig model is relevant for
      malnourished infants and can act as a valuable tool for understanding the
      pathophysiology of malnutrition. 

PMID- 23977414
TI  - Annexin A6 is down-regulated through promoter methylation in gastric cancer.
AB  - BACKGROUND: The aberrant activation of oncogenic signaling such as Ras/MAPK
      signaling is a frequent event in human cancers. In addition to genetic changes,
      epigenetic silencing of inhibitors in Ras/MAPK signaling contributes to the
      activation of Ras/MAPK signaling. Recently, ANXA6 has been shown to interact with
      Ras-GAP1 and inhibit Ras activation in human breast cancer. However, whether and
      how it is involved in human cancers remain unknown. METHODS: Real-time PCR was
      used to determine ANXA6 expression in gastric cancer cells and primary gastric
      carcinomas. Next, we explored the methylation of ANXA6 promoter in cell lines and
      tumor tissues with methylation-specific PCR and bisulfite genomic sequencing. We
      also investigated the function of ANXA6 in gastric cancer cells with colony
      formation assay and western blotting analysis. RESULTS: ANXA6 was down-regulated
      in gastric cancer cells and primary gastric carcinomas. Ectopic ANXA6 expression
      inhibited the growth of gastric cancer cells and the activity of Ras/MAPK
      signaling. Its expression was restored after pharmaceutical demethylation. ANXA6
      promoter was methylated in gastric cancer cell lines (6/6) and primary gastric
      carcinoma tissues (29/156). Interestingly, the knockdown of oncoprotein Yin Yang
      1 (YY1) also restored ANXA6 expression and promoted the demethylation of ANXA6
      promoter. However, ANXA6 methylation was not associated with clinical parameters
      such as differentiation, and TNM staging. Neither Kaplan-Meier Curve nor Cox
      regression analysis revealed a significant role of ANXA methylation to predict
      the survival of gastric cancer patients. CONCLUSIONS: We firstly reported that
      ANXA6 is epigenetically silenced through promoter methylation in human cancers
      and YY1 is important to initiate or maintain ANXA6 promoter methylation in
      gastric cancer cells. ANXA6 functions as a tumor suppressor in gastric cancer
      cells through the inhibition of Ras/MAPK signaling. ANXA6 methylation is not a
      prognostic factor for gastric cancer patients.

PMID- 23977415
TI  - Is Asian American Parenting Controlling and Harsh? Empirical Testing of
      Relationships between Korean American and Western Parenting Measures.
AB  - Asian American parenting is often portrayed as highly controlling and even harsh.
      This study empirically tested the associations between a set of recently
      developed Korean ga-jung-kyo-yuk measures and several commonly used Western
      parenting measures to accurately describe Asian American family processes,
      specifically those of Korean Americans. The results show a much nuanced and
      detailed picture of Korean American parenting as a blend of Western authoritative
      and authoritarian styles with positive and-although very limited-negative
      parenting. Certain aspects of ga-jung-kyo-yuk are positively associated with
      authoritative style or authoritarian style, or even with both of them
      simultaneously. They were positively associated with positive parenting (warmth,
      acceptance, and communication) but not with harsh parenting (rejection and
      negative discipline). Exceptions to this general pattern were Korean traditional
      disciplinary practices and the later age of separate sleeping of children. The
      study discusses implications of these findings and provides suggestions for
      future research.

PMID- 23977416
TI  - Optimization of Arylamides as Novel, Potent and Brain-penetrant Antiprion Lead
      Compounds.
AB  - The prion diseases caused by PrPSc, an alternatively folded form of the cellular
      prion protein (PrPC), are rapidly progressive, fatal, and untreatable
      neurodegenerative syndromes. We employed HTS ELISA assays to identify compounds
      that lower the level of PrPSc in prion-infected mouse neuroblastoma (ScN2a-cl3)
      cells and identified a series of arylamides. SAR studies indicated that small
      amides with one aromatic, or heteroaromatic ring, on each side of the amide bond
      are of modest potency. Of note, benzamide (7), with an EC50 of 2200 nM, was one
      of only a few arylamide hits with a piperazine group on its aniline moiety. The
      basic piperazine nitrogen can be protonated at physiologic pH, improving
      solubility, and therefore we wanted to exploit this feature in our search for a
      drug candidate. An SAR campaign resulted in several key analogs, including a set
      with biaryl groups introduced on the carbonyl side for improved potency. Several
      of these biaryl analogs have submicromolar potency, with the most potent analog
      17 having an EC50 = 22 nM. More importantly, 17 and several biarylamides (20, 24,
      26, 27) were able to traverse the BBB and displayed excellent drug levels in the
      brains of mice following oral dosing. These biarylamides may represent good
      starting points for further lead optimization for the identification of potential
      drug candidates for the treatment of prion diseases.

PMID- 23977417
TI  - Minimally invasive treatment of cholecysto-choledocal lithiasis: The point of
      view of the surgical endoscopist.
AB  - The rate of choledocholithiasis in patients with symptomatic cholelithiasis is
      estimated to be approximately 10%-33%, depending on the patient's age.
      Development of Endoscopic Retrograde Cholangiopancreatography and Laparoscopic
      Surgery and improvement of diagnostic procedures have influenced new approaches
      to the management of common bile duct stones in association with gallstones. At
      present available minimally-invasive treatments of cholecysto-choledocal
      lithiasis include: single-stage laparoscopic treatment, perioperative endoscopic
      treatment and endoscopic treatment alone. Published data evidence that,
      associated endoscopic-laparoscopic approach necessitates increased number of
      procedures per patient while single-stage laparoscopic treatment is associated
      with a shorter hospital stay. However, current data does not suggest clear
      superiority of any one approach with regard to success, mortality, morbidity and
      cost-effectiveness. Considering the variety of therapeutic options available for
      management, a critical appraisal and decision-making is required. Endoscopic
      retrograde cholangiopancreatography/EST should be adopted on a selective basis,
      i.e., in patients with acute obstructive suppurative cholangitis, severe biliary
      pancreatitis, ampullary stone impaction or severe comorbidity. In a setting where
      all facilities are available, decision in the selection of the therapeutic option
      depends on the patients, the number and size of choledocholithiasis stones, the
      anatomy of the cystic duct and common bile duct, the surgical history of patients
      and local expertise. 

PMID- 23977418
TI  - Current status of surgical treatment for fulminant clostridium difficile colitis.
AB  - Mortality rates attributable to fulminant Clostridium difficile (C. difficile)
      colitis remain high and are reported to be 38%-80%. Historically, the threshold
      for surgical intervention has been judged empirically because level I evidence to
      guide decision making is lacking. Studies of the surgical management of C.
      difficile infection have been limited by small sample size and the lack of a
      standard definition of fulminancy. Multiple small and medium-sized series have
      examined the surgical management of C. difficile. However, because of a lack of
      prospective, randomized studies, it has been difficult to identify the optimal
      point for surgical intervention in patients with severe fulminant C. difficile
      colitis. Our goal was to analyze the existing body of literature in an attempt to
      define host constellations, which would predict the development of the more
      aggressive form of this disease and hence justify an early or earlier surgical
      intervention. A Pubmed search was conducted using the keywords "fulminant",
      "clostridium difficile", "surgery", and "colitis". Reviews and meta-analyses
      proposing indications for surgical consultation or operative management in
      patients with C. difficile colitis were included. After analyzing current
      literature, we identified a number of parameters that are associated with
      unfavorable outcomes. The parameters include age greater than 65 years old,
      peritoneal signs on physical examination, abdominal distension, signs of end
      organ failure, hypotension less than 90 mmHg systolic blood pressure, tachycardia
      greater than 100 bpm, vasopressor requirement, elevated WBC count of greater than
      at least 16 * 10(9)/MUL, serum lactate of greater than 2.2 mmol/L, and lastly,
      radiologic findings suggestive of pancolitis, ascites, megacolon, or colonic
      perforation. Even though fairly strong evidence exists in contemporary
      literature, we recommend use of these identified parameters with caution in
      clinical practice when it comes to the actual decision to treat certain patients
      more aggressively. The identified risk factors should be used to lower surgeons'
      threshold for operative treatment early in the course of the disease. 

PMID- 23977419
TI  - Caudal approach to pure laparoscopic posterior sectionectomy under the
      laparoscopy-specific view.
AB  - AIM: To study our novel caudal approach laparoscopic posterior-sectionectomy with
      parenchymal transection prior to mobilization under laparoscopy-specific view.
      METHODS: Points of the procedure are: (1) Patients are put in left lateral
      position and posterior sector is not mobilized; (2) Glissonian pedicle of the
      sector is encircled and clamped extra-hepatically and divided afterward during
      the transection; (3) Dissection of inferior vena cava (IVC) anterior wall behind
      the liver is started from caudal. Simultaneously, liver transection is performed
      to search right hepatic vein (RHV) from caudal; (4) Liver transection proceeds to
      the bifurcation of the vessels from caudal to cranial, exposing the surfaces of
      IVC and RHV. Since the remnant liver sinks down, the cutting surface is well
      opend; and (5) After the completion of transection, dissection of the resected
      liver from retroperitoneum is easily performed using the gravity. This approach
      was performed for a 63 years old woman with liver metastasis close to RHV.
      RESULTS: RHV exposure is required for R0 resection of the lesion. Although the
      cutting plane is horizontal in supine position and the gravity obstructs the
      exposure in the small subphrenic space, the use of specific characteristics of
      laparoscopic hepatectomy, such as the good vision for the dorsal part of the
      liver and IVC and facilitated dissection using the gravity with the patient
      positioning, made the complete RHV exposure during the liver transection easy to
      perform. The operation time was 341 min and operative blood loss was 1356 mL. Her
      postoperative hospital stay was uneventfull and she is well without any signs of
      recurrences 14 mo after surgery. CONCLUSION: The new procedure is feasible and
      useful for the patients with tumors close to RHV and the need of the exposure of
      RHV.

PMID- 23977420
TI  - Impact of medical and surgical intervention on survival in patients with
      cholangiocarcinoma.
AB  - AIM: To examine surgical and medical outcomes for patients with
      cholangiocarcinoma using a population-based cancer registry. METHODS: Using the
      California Cancer Registry's Cancer Surveillance Program, patients with
      intrahepatic cholangiocarcinoma treated in Los Angeles County from 1988 to 2006
      were identified and evaluated for clinical and pathologic factors and therapies
      received (surgery, radiation, and chemotherapy). The surgical cohort was further
      categorized into three treatment groups: patients who received adjuvant
      chemotherapy, adjuvant chemoradiation, or underwent surgery alone (no
      chemotherapy or radiation administered). Survival was assessed by Kaplan-Meier
      method; and Cox proportional hazard modeling was used in multivariate analysis.
      RESULTS: Of 825 patients, 60.2% received no treatment. Of the remaining 328
      patients, 18.5% chemotherapy only, 7.4% chemoradiation, and 13.8% underwent
      surgery. More male patients underwent surgical resection (P = 0.004). Surgical
      patients were younger than the patients receiving chemotherapy or chemoradiation
      (P < 0.001). Of the surgical cohort (n = 114), 60.5% underwent surgery alone
      while 39.5% underwent surgery plus adjuvant therapy (chemotherapy, n = 20;
      chemoradiation, n = 21) (P < 0.001). Median survival for all patients in the
      study was 6.6 mo. Median survival was highest for patients who underwent surgery
      (23 mo), whereas both chemotherapy (9 mo) and chemoradiation (8 mo) alone were
      each less effective (P < 0.001). By multivariate analysis, extent of disease,
      receipt of surgery, and administration of chemotherapy (with/without surgery)
      were independent predictors of overall survival. CONCLUSION: This study
      demonstrates that surgery is a critical treatment modality. Multimodality
      treatment has yet to be standardized, but play a role in optimal therapy for
      cholangiocarcinoma.

PMID- 23977422
TI  - Autophagy and cancer.
AB  - Autophagy is a homeostatic and evolutionarily conserved mechanism of self
      digestion by which the cells degrade and recycle long-lived proteins and excess
      or damaged organelles. Autophagy is activated in response to both physiological
      and pathological stimuli including growth factor depletion, energy deficiency or
      the upregulation of Bcl-2 protein expression. A novel role of autophagy in
      various cancers has been proposed. Interestingly, evidence that supports both a
      positive and negative role of autophagy in the pathogenesis of cancer has been
      reported. As a tumor suppression mechanism, autophagy maintains genome stability,
      induces senescence and possibly autophagic cell death. On the other hand,
      autophagy participates in tumor growth and maintenance by supplying metabolic
      substrate, limiting oxidative stress, and maintaining cancer stem cell
      population. It has been proposed that the differential roles of autophagy in
      cancer are disease type and stage specific. In addition, substrate selectivity
      might be involved in carrying out the specific effect of autophagy in cancer, and
      represents one of the potential directions for future studies. 

PMID- 23977421
TI  - Molecular recognition by gold, silver and copper nanoparticles.
AB  - The intrinsic physical properties of the noble metal nanoparticles, which are
      highly sensitive to the nature of their local molecular environment, make such
      systems ideal for the detection of molecular recognition events. The current
      review describes the state of the art concerning molecular recognition of Noble
      metal nanoparticles. In the first part the preparation of such nanoparticles is
      discussed along with methods of capping and stabilization. A brief discussion of
      the three common methods of functionalization: Electrostatic adsorption;
      Chemisorption; Affinity-based coordination is given. In the second section a
      discussion of the optical and electrical properties of nanoparticles is given to
      aid the reader in understanding the use of such properties in molecular
      recognition. In the main section the various types of capping agents for
      molecular recognition; nucleic acid coatings, protein coatings and molecules from
      the family of supramolecular chemistry are described along with their numerous
      applications. Emphasis for the nucleic acids is on complementary oligonucleotide
      and aptamer recognition. For the proteins the recognition properties of
      antibodies form the core of the section. With respect to the supramolecular
      systems the cyclodextrins, calix[n]arenes, dendrimers, crown ethers and the
      cucurbitales are treated in depth. Finally a short section deals with the
      possible toxicity of the nanoparticles, a concern in public health. 

PMID- 23977423
TI  - Potent trophic activity of spermidine supramolecular complexes in in vitro
      models.
AB  - AIM: To test the growth-promoting activity of the polyamine spermidine bound to
      various polymeric compounds in supramolecular complexes. METHODS: A thiazolyl
      blue cell viability assay was used to determine the growth-promoting potency of
      spermidine-supramolecular complexes in a human skin fibroblast cell line exposed
      to spermidine and different spermidine-supramolecular complexes that were
      obtained by combining spermidine and polyanionic polymers or cyclodextrin.
      Reconstituted human vaginal epithelium was exposed to a specific spermidine
      supramolecular complex, i.e., spermidine-hyaluronan (HA) 50, and cell
      proliferation was determined by Ki-67 immunohistochemical detection.
      Transepithelial electrical resistance and histological analysis were also
      performed on reconstituted human vaginal epithelium to assess tissue integrity.
      RESULTS: The effect of spermidine and spermidine-supramolecular complexes was
      first tested in skin fibroblasts. Spermidine displayed a reverse dose-related
      mode of activity with mmol/L growth inhibition, whereas 30% stimulation over
      basal levels was detected at MUmol/L and nmol/L levels. Novel spermidine
      supramolecular complexes that formed between spermidine and polyanionic polymers,
      such as HA, alginate, and polymaleate, were then tested at variable spermidine
      concentrations and a fixed polymer level (0.1% w/v). Spermidine-supramolecular
      complexes stimulated the cell growth rate throughout the entire concentration
      range with maximal potency (up to 80%) at sub-MUmol/L levels. Similar results
      were obtained with spermidine-(alpha-cyclodextrin), another type of spermidine
      supramolecular complex. Moreover, the increased expression of Ki-67 in the
      reconstituted human vaginal epithelium exposed to spermidine-HA 50 showed that
      the mode of action behind the spermidine-supramolecular complexes was increased
      cell proliferation. Functional and morphological assessments of reconstituted
      human vaginal epithelium integrity did not show significant alterations after
      exposure to spermidine-HA, thus supporting its safety. CONCLUSION: Spermidine
      found in spermidine-supramolecular complexes displayed potentiated regenerative
      effects. Safety data on reconstituted human vaginal epithelium suggested that
      assessing spermidine-supramolecular complex efficacy in atrophic disorders is
      justified.

PMID- 23977424
TI  - What makes a life event traumatic for a child? The predictive values of DSM
      Criteria A1 and A2.
AB  - BACKGROUND: The Diagnostic and Statistical Manual of Mental Disorders (DSM)
      Criteria A1 and A2 for posttraumatic stress disorder (PTSD) have been discussed
      extensively, with several studies in adults or adolescents supporting the removal
      of Criterion A2. However, solid research in children is missing. OBJECTIVE: This
      study evaluated the DSM-Criteria A1 and A2 in predicting posttraumatic stress in
      children. METHOD: A sample of 588 Dutch school children, aged 8-18 years,
      completed a self-report questionnaire to determine if they met Criteria A1 and/or
      A2. Their posttraumatic stress response was assessed using the Children's Revised
      Impact of Event Scale. RESULTS: The contribution of Criterion A2 to the
      prediction of posttraumatic stress in children is of greater importance than the
      contribution of Criterion A1. Children who met Criterion A2 reported
      significantly higher levels of posttraumatic stress and were nine times more
      likely to develop probable PTSD than children who did not meet Criterion A2. When
      Criterion A1 was met, a child was only two times more likely to develop probable
      PTSD as compared with those where Criterion A1 was not met. Furthermore, the low
      sensitivity of Criterion A1 suggests that children may regularly develop severe
      posttraumatic stress in the absence of Criterion A1. The remarkably high negative
      predictive value of Criterion A2 indicates that if a child does not have a
      subjective reaction during an event that it is unlikely that he or she will
      develop PTSD. CONCLUSIONS: In contrast to most adult studies, the findings of
      this study emphasize the significant contribution of Criterion A2 to the
      prediction of posttraumatic stress in children and raise fundamental questions
      about the value of the current Criterion A1.

PMID- 23977425
TI  - Messages from the Terrae Cognitae of Culture, Development, and Parenting.

PMID- 23977426
TI  - Exploitation of adaptive evolution in glioma treatment.
AB  - Glioblastoma multiforme (GBM) is a malignant neoplasm of the CNS with almost
      uniform lethality. Even with standard-of-care treatments, the prognosis for
      patients remains dismal. GBM, as with other malignancies, often acquires
      treatment resistance after an initial response to therapy. Treatment resistance
      may come about through the adaptive evolution of tumors in response to selection
      pressures from treatment interventions and the microenvironment. This review
      discusses how adaptive evolution might potentially be exploited as a new paradigm
      in GBM treatment.

PMID- 23977427
TI  - Citrate-based Biodegradable Injectable hydrogel Composites for Orthopedic
      Applications.
AB  - Previous studies have confirmed that natural bone apatite crystals are bound with
      citrate-rich molecules. Citrates on apatite crystals impact bone development and
      its load-bearing function. However, such understanding has never been translated
      into bone biomaterials design. Herein, a first citrate-based injectable composite
      material for orthopedic applications is developed based on our recently developed
      biodegradable poly(ethylene glycol) maleate citrate (PEGMC) and hydroxyapatite
      (HA). PEGMC contains rich carboxylic groups that could chelate with calcium
      containing HA thus facilitating polymer/HA interactions, similar to natural
      citrate-bound apatite crystal. The crosslinking of poly(ethylene glycol)
      diacrylate (PEGDA) with PEGMC/HA composites allows an addition control over
      degradation and mechanical properties of the crosslinked PEGMC/HA (CPEGMC/HA)
      composites. CPEGMC/HA composite can serve as an ideal injectable cell carrier as
      confirmed by the enhanced DNA content, ALP activity, and calcium production
      through a human fetal osteoblast encapsulation study. Ex vivo study on porcine
      femoral head demonstrated that PEGMC/HA is a potentially promising injectable
      biodegradable bone material for the treatment of osteonecrosis of the femoral
      head. Development of biodegradable citrate-based injectable PEGMC/HA composite is
      an initial step for the development of the next generation of bone tissue
      engineering and orthopedic biomaterials.

PMID- 23977428
TI  - Adenosine A1 receptor signaling inhibits BK channels through a PKCalpha-dependent
      mechanism in mouse aortic smooth muscle.
AB  - Adenosine receptors (AR; A1, A2A, A2B, and A3) contract and relax smooth muscle
      through different signaling mechanisms. Deciphering these complex responses
      remains difficult because relationships between AR subtypes and various end
      effectors (e.g., enzymes and ion channels) remain to be identified. A1AR
      stimulation is associated with the production of 20-hydroxyeicosatetraenoic acid
      (20-HETE) and activation of protein kinase C (PKC). 20-HETE and PKC can inhibit
      large conductance Ca2+/voltage-sensitive K+ (BK) channels that regulate smooth
      muscle contraction. We tested the hypothesis that activation of A1AR inhibits BK
      channels via a PKC-dependent mechanism. Patch clamp recordings and Western blots
      were performed using aortae of wild type (WT) and A1AR knockout (A1KO) mice.
      There were no differences in whole-cell K+ current or alpha and beta1 subunits
      expression between WT and A1KO. 20-HETE (100 nM) inhibited BK current similarly
      in WT and A1KO mice. NECA (5'-N-ethylcarboxamidoadenosine; 10 MUM), a non
      selective AR agonist, increased BK current in myocytes from both WT and A1KO
      mice, but the increase was greater in A1KO (52+/-15 vs. 17+/-3%; p<0.05). This
      suggests that A1AR signaling negatively regulates BK channel activity.
      Accordingly, CCPA (2-chloro-N(6)-cyclopentyladenosine; 100 nM), an A1AR-selective
      agonist, inhibited BK current in myocytes from WT but not A1KO mice (81+/-4 vs.
      100+/-7% of control; p<0.05). Go6976 (100 nM), a PKCalpha inhibitor, abolished
      the effect of CCPA to inhibit BK current (99+/-3% of control). These data lead us
      to conclude that, in aortic smooth muscle, A1AR inhibits BK channel activity and
      that this occurs via a mechanism involving PKCalpha.

PMID- 23977429
TI  - From SARS coronavirus to novel animal and human coronaviruses.
AB  - In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) caused one of
      the most devastating epidemics known to the developed world. There were two
      important lessons from this epidemic. Firstly, coronaviruses, in addition to
      influenza viruses, can cause severe and rapidly spreading human infections.
      Secondly, bats can serve as the origin and natural animal reservoir of deadly
      human viruses. Since then, researchers around the world, especially those in Asia
      where SARS-CoV was first identified, have turned their focus to find novel
      coronaviruses infecting humans, bats, and other animals. Two human coronaviruses,
      HCoV-HKU1 and HCoV-NL63, were identified shortly after the SARS-CoV epidemic as
      common causes of human respiratory tract infections. In 2012, a novel human
      coronavirus, now called Middle East respiratory syndrome coronavirus (MERS-CoV),
      has emerged in the Middle East to cause fatal human infections in three
      continents. MERS-CoV human infection is similar to SARS-CoV in having a high
      fatality rate and the ability to spread from person to person which resulted in
      secondary cases among close contacts including healthcare workers without travel
      history to the Middle East. Both viruses also have close relationships with bat
      coronaviruses. New cases of MERS-CoV infection in humans continue to occur with
      the origins of the virus still unknown in many cases. A multifaceted approach is
      necessary to control this evolving MERS-CoV outbreak. Source identification
      requires detailed epidemiological studies of the infected patients and enhanced
      surveillance of MERS-CoV or similar coronaviruses in humans and animals. Early
      diagnosis of infected patients and appropriate infection control measures will
      limit the spread in hospitals, while social distancing strategies may be
      necessary to control the outbreak in communities if it remained uncontrolled as
      in the SARS epidemic. 

PMID- 23977430
TI  - Influenza seasonality and predominant subtypes of influenza virus in Guangdong,
      China, 2004-2012.
AB  - BACKGROUND: Influenza surveillance is carried out in Guangdong province, southern
      China. A better understanding of influenza seasonality and predominant Subtypes
      of influenza virus in Guangdong can help to improve evidence-based prevention and
      control strategies for influenza in the future. MATERIALS AND METHODS: THERE ARE
      THREE CATEGORIES OF INFLUENZA SURVEILLANCE IN GUANGDONG: Influenza-like Illness
      (ILI) Outpatient Surveillance, ILI Outbreak Surveillance and Influenza Virus
      Surveillance. This paper summarizes collected influenza surveillance data from
      January 2004 to December 2012 in Guangdong province. Time series analysis and
      "peak analysis" were performed to estimate seasonality and temporal trends of
      influenza activity. RESULTS: During the 9-year study period, a total of
      37,571,582 outpatients had been recorded, in which 1,889,684 ILI cases had been
      reported. The provincial ILI visiting percentage peaked at 6-10%. A total of
      107,115 respiratory specimens of ILI outpatients were collected, 17,454 (16.29%)
      of them tested for influenza virus were positive. Influenza virus peaks appeared
      in summer mostly with a median epidemic duration of 6 months. A total of 925
      outbreaks recorded and 45,322 cases in which were affected. The majority of
      reported outbreaks (832 outbreaks, 90%) occurred in institutional settings.
      CONCLUSIONS: Influenza circulates periodically every year in Guangdong. Influenza
      activity had strong and clear seasonality with epidemic periods in summer for
      last decade. The presence of local unique seasonal pattern and its changes
      emphasizes the need to optimize timing of influenza vaccine delivery and other
      public health interventions.

PMID- 23977431
TI  - Tracing the SARS-coronavirus.
AB  - Four coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1) are endemic in
      humans and mainly associated with mild respiratory illnesses; whereas the other
      two coronaviruses [Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and
      Middle East Respiratory Syndrome Coronavirus (MERS-CoV)] present as emerging
      infections causing severe respiratory syndrome. Coronaviruses evolve by
      accumulation of point mutations and recombination of genomes among different
      strains or species. Mammalian coronaviruses including those infect humans are
      evolved from bat coronaviruses. While SARS-CoV and MERS-CoV are genetically
      closely related to bat coronaviruses, intermediate host(s) is (are) likely to be
      involved in the emergence and cross-species transmission of these novel human
      viruses. High prevalence of SARS-like coronaviruses have been found from masked
      palm civet cats and raccoon dogs collected from markets around the time of
      outbreaks in humans, but these animals are likely to be a transient accidental
      host rather than a persisting reservoir. More research is needed to elucidate the
      ecology of coronaviruses. Vigilance and surveillance should be maintained to
      promptly identify newly emerged coronaviruses. 

PMID- 23977432
TI  - Severe acute respiratory syndrome (SARS): lessons learnt in Hong Kong.
AB  - Many healthcare workers were infected while looking after the SARS patients on
      the medical wards in 2003. The high infectivity of the SARS coronavirus with peak
      viral load on day 10 of illness when patients were ill, overcrowding of the old
      medical wards with low air changes/hr (ACH), and aerosol-generating procedures
      while resuscitating the patients were the major factors. Procedures reported to
      present an increased risk of SARS transmission include tracheal intubation, non
      invasive ventilation, tracheotomy and manual ventilation before intubation
      whereas oxygen therapy and bed distance <1 m were also implicated. Studies based
      on laser visualization technique with smoke particles as smokers in the human
      patient simulator has shown that oxygen therapy via Hudson mask and nasal cannula
      could disperse exhaled air of patients to 0.4 and 1 m respectively whereas jet
      nebulizer could disperse exhaled air >0.8 m from the patient. Bigger isolation
      rooms with 16 ACH are more effective than smaller isolation rooms with 12 ACH in
      removing exhaled air and preventing room contamination but at the expense of more
      noise and electricity consumption. Non-invasive ventilation via face masks and
      single circuit can disperse exhaled air from 0.4 to 1 m. Both higher inspiratory
      pressures and use of whisper swivel device (to facilitate carbon dioxide removal)
      could increase the exhaled air leakage and isolation room contamination during on
      invasive ventilation. Addition of a viral-bacterial filter during manual
      ventilation by bagging may reduce the exhaled air leakage forward and yet
      increase the sideway leakage. N95 mask was more effective than surgical mask in
      preventing expelled air leakage during patient's coughing but there was still
      significant sideway leakage to 15 cm. Clinicians should be aware of air leakage
      from the various face masks and adopt strict infection control measures during
      resuscitation of patients with severe respiratory infections. Carefully designed
      clinical trials are required to determine the optimal timing and dosage of any
      antiviral agents, convalescent plasma, and immuno-modulating agents in the
      treatment of the possibly immune-mediated lung injury in SARS and newly emerged
      infection such as the Middle East Respiratory Syndrome. 

PMID- 23977433
TI  - The human microbiota: a new direction in the investigation of thoracic diseases.
AB  - Advancements in next generation sequencing technology have provided means for the
      comprehensive profiling of the microbial community in the respiratory tract in
      both physiological and pathological conditions. Recent studies have analyzed the
      bacterial composition in the respiratory tract of chronic obstructive pulmonary
      disease (COPD), influenza and tuberculosis patients, and have identified novel
      targets that may potentially lead to secondary infections. Certain bacteria have
      also been found to regulate the lung immune system and have unexpected
      connections with respiratory diseases. Further studies in these areas are
      necessary to dissect the exact relationship between the dynamics of the
      microbiota and the health of the respiratory system. 

PMID- 23977435
TI  - Receptor-binding domain as a target for developing SARS vaccines.
AB  - A decade ago, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV)
      caused a global pandemic with a mortality rate of 10%. Reports of recent
      outbreaks of a SARS-like disease caused by Middle East respiratory syndrome
      coronavirus (MERS-CoV) have raised serious concerns of a possible reemergence of
      SARS-CoV, either by laboratory escape or the presence of a natural reservoir.
      Therefore, the development of effective and safe SARS vaccines is still needed.
      Based on our previous studies, we believe that the receptor-binding domain (RBD)
      in the S1 subunit of the SARS-CoV spike (S) protein is the most important target
      for developing a SARS vaccine. In particular, RBD of S protein contains the
      critical neutralizing domain (CND), which is able to induce highly potent
      neutralizing antibody response and cross-protection against divergent SARS-CoV
      strains. Furthermore, a RBD-based subunit vaccine is expected to be safer than
      other vaccines that may induce Th2-type immunopathology. This review will discuss
      key advances in the development of RBD-based SARS vaccines and the possibility of
      using a similar strategy to develop vaccines against MERS-CoV. 

PMID- 23977434
TI  - Influenza A induced cellular signal transduction pathways.
AB  - Influenza A is a negative sense single stranded RNA virus that belongs to the
      Orthomyxoviridae Family. This enveloped virus contains 8 segments of viral RNA
      which encodes 11 viral proteins. Influenza A infects humans and is the causative
      agent of the flu. Annually it infects approximately 5% to 15% of the population
      world wide and results in an estimated 250,000 to 500,000 deaths a year. The
      nature of influenza A replication results in a high mutation rate which results
      in the need for seasonal vaccinations. In addition the zoonotic nature of the
      influenza virus allows for recombination of viral segments from different strains
      creating new variants that have not been encountered before. This type of
      mutation is the method by which pandemic strains of the flu arises. Infection
      with influenza results in a respiratory illness that for most individuals is self
      limiting. However in susceptible populations which include individuals with pre
      existing pulmonary or cardiac conditions, the very young and the elderly fatal
      complications may arise. The most serious of these is the development of viral
      pneumonia which may be accompanied by secondary bacterial infections. Progression
      of pneumonia leads to the development of acute respiratory distress syndrome
      (ARDS), acute lung injury (ALI) and potentially respiratory failure. This
      progression is a combined effect of the host immune system response to influenza
      infection and the viral infection itself. This review will focus on molecular
      aspects of viral replication in alveolar cells and their response to infection.
      The response of select innate immune cells and their contribution to viral
      clearance and lung epithelial damage will also be discussed. Molecular aspects of
      antiviral response in the cells in particular the protein kinase RNA dependent
      response, and the oligoadenylate synthetase RNAse L system in relation to
      influenza infection. 

PMID- 23977437
TI  - Professor Stephen Kwok-Wing Tsui: targeting pathogen genomes.

PMID- 23977438
TI  - Ten years after SARS: where was the virus from?

PMID- 23977439
TI  - Guideline on prevention and control of H7N9 avian influenza human infection.

PMID- 23977436
TI  - Novel hemagglutinin-based influenza virus inhibitors.
AB  - Influenza virus has caused seasonal epidemics and worldwide pandemics, which
      caused tremendous loss of human lives and socioeconomics. Nowadays, only two
      classes of anti-influenza drugs, M2 ion channel inhibitors and neuraminidase
      inhibitors respectively, are used for prophylaxis and treatment of influenza
      virus infection. Unfortunately, influenza virus strains resistant to one or all
      of those drugs emerge frequently. Hemagglutinin (HA), the glycoprotein in
      influenza virus envelope, plays a critical role in viral binding, fusion and
      entry processes. Therefore, HA is a promising target for developing anti
      influenza drugs, which block the initial entry step of viral life cycle. Here we
      reviewed recent understanding of conformational changes of HA in protein folding
      and fusion processes, and the discovery of HA-based influenza entry inhibitors,
      which may provide more choices for preventing and controlling potential pandemics
      caused by multi-resistant influenza viruses. 

PMID- 23977440
TI  - Severe acute respiratory syndrome: a vanished evil?

PMID- 23977441
TI  - Chance missed, but still there! Memoirs at the 10(th) anniversary of 2003 SARS
      outbreak.

PMID- 23977442
TI  - Behavioral Science Research Informs Bioethical Issues in the Conduct of Large
      Scale Studies of Children's Disease Risk.
AB  - BACKGROUND: Birth cohort studies of the natural history of pediatric common
      disease risk raise many bioethical issues, including re-consenting participants
      over time as children mature and cohort retention. Understanding participants'
      study-specific knowledge, attitudes, beliefs, and behavior may offer insights
      into these issues from a psychological perspective. METHODS: We conducted an
      analysis of factors associated with parent-child communication about minor
      children's participation in a population-based birth cohort; children's knowledge
      about their own participation; and parental willingness to be re-contacted for
      future study among Swedish parents (N = 3,605) of children originally enrolled at
      birth in a prospective study of type 1 diabetes risk. RESULTS: More open parent
      child communication about disease risk screening research and greater knowledge
      among children about their own research participation facilitated greater parent
      willingness to participate in further study. Parents' decisions about further
      study participation were most strongly favorable among those who communicated
      openly with their child and with high study-specific knowledge. CONCLUSIONS:
      Epidemiologists, bioethicists, and others involved in the design and conduct of
      large-scale, prospective birth cohorts may consider embedding periodic
      assessments of participants' study-specific attitudes and behavior to address
      long-term retention and willingness to engage in future research.

PMID- 23977444
TI  - Nuclear transcription factor Y and its roles in cellular processes related to
      human disease.
AB  - Nuclear transcription factor Y (NF-Y) is an example of a transcriptional
      regulation factor in eukaryotes consisting of three different subunits, NF-YA, NF
      YB and NF-YC, which are all necessary for formation of NF-Y complexes and binding
      to CCAAT boxes in promoters of its target genes. Highly conserved between human
      and Drosophila, NF-Y regulates transcription of various genes related to the cell
      cycle and various human diseases. Drosophila models have been widely used as
      tools for studying genetics and developmental biology and more recently for
      analyzing the functions of human disease genes, including those responsible for
      developmental and neurological disorders, cancer, cardiovascular disease and
      metabolic and storage diseases, as well as genes required for function of the
      visual, auditory and immune systems. In this review, in vivo findings from
      Drosophila models relevant to the roles of NF-Y in various human diseases are
      summarized. Recent studies have demonstrated novel contributions of dNF-Y to
      apoptosis and apoptosis-induced proliferation, and in photoreceptor cell
      differentiation during the development of the Drosophila compound eye. 

PMID- 23977443
TI  - Isoforms of Vitamin E Differentially Regulate PKC alpha and Inflammation: A
      Review.
AB  - Vitamin E regulation of disease has been extensively studied but most studies
      focus on the alpha-tocopherol isoform of vitamin E. These reports indicate
      contradictory outcomes for anti-inflammatory functions of the alpha-tocopherol
      isoform of vitamin E with regards to animal and clinical studies. These seemingly
      disparate results are consistent with our recent studies demonstrating that
      purified natural forms of vitamin E have opposing regulatory functions during
      inflammation. In this review, we discuss that alpha-tocopherol inhibits whereas
      gamma-tocopherol elevates allergic inflammation, airway hyperresponsiveness,
      leukocyte transendothelial migration, and endothelial cell adhesion molecule
      signaling through protein kinase Calpha. Moreover, we have demonstrated that
      alpha-tocopherol is an antagonist and gamma-tocopherol is an agonist of PKCalpha
      through direct binding to a regulatory domain of PKCalpha. In summary, we have
      determined mechanisms for opposing regulatory functions of alpha-tocopherol and
      gamma-tocopherol on inflammation. Information from our studies will have
      significant impact on the design of clinical studies and on vitamin E
      consumption.

PMID- 23977445
TI  - BLT2 is a pro-tumorigenic mediator during cancer progression and a therapeutic
      target for anti-cancer drug development.
AB  - Cancer is a leading cause of death worldwide and has been linked to inflammation.
      Leukotriene B4 (LTB4) is synthesized from arachidonic acid via the 5-lipoxygenase
      pathway and is a potent chemoattractant for inflammatory cells. LTB4 was recently
      shown to be associated with the pathogenesis of inflammatory diseases, including
      cancer. Of the two known LTB4 receptors, BLT1 and BLT2, the biological roles of
      the low-affinity LTB4 receptor 2, BLT2, have only recently been elucidated. This
      review focuses on recent discoveries regarding BLT2 and its roles in cancer
      progression and the downstream signaling mechanisms of the BLT2-linked signaling
      cascade in cancer cells. We believe that these findings will facilitate the
      development of new cancer treatments. 

PMID- 23977446
TI  - Kruppel-like factor 8 promotes tumorigenic mammary stem cell induction by
      targeting miR-146a.
AB  - The properties of stem cells can be induced during the epithelial to mesenchymal
      transition (EMT). The responsible molecular mechanisms, however, remain largely
      undefined. Here we report the identification of the microRNA-146a (miR-146a) as a
      common target of Kruppel-like factor 8 (KLF8) and TGF-beta, both of which are
      known EMT-inducers. Upon KLF8 overexpression or TGF-beta treatment, a significant
      portion of the MCF-10A cells gained stem cell traits as demonstrated by an
      increased expression of CD44(high)/CD24low, activity of aldehyde dehydrogenase
      (ALDH), mammosphere formation and chemoresistance. Along with this change, the
      expression of miR-146a was highly upregulated in the cells. Importantly, we found
      that miR-146a was aberrantly co-overexpressed with KLF8 in a panel of invasive
      human breast cancer cell lines. Ectopic expression of KLF8 failed to induce the
      stem cell traits in the MCF-10A cells if the cells were pre-treated with miR-146a
      inhibitor, whereas overexpression of miR-146a in the MCF-10A cells alone was
      sufficient to induce the stem cell traits. Co-staining and luciferase reporter
      analyses indicated that miR-146a targets the 3'-UTR of the Notch signaling
      inhibitor NUMB for translational inhibition. Overexpression of KLF8 dramatically
      potentiated the tumorigenecity of MCF-10A cells expressing the H-Ras oncogene,
      which was accompanied by a loss of NUMB expression in the tumors. Taken together,
      this study identifies a novel role and mechanism for KLF8 in inducing pro
      tumorigenic mammary stem cells via miR-146a potentially by activating Notch
      signaling. This mechanism could be exploited as a therapeutic target against drug
      resistance of breast cancer. 

PMID- 23977447
TI  - Effect of epigenetic histone modifications on E-cadherin splicing and expression
      in lung cancer.
AB  - We have identified an alternatively spliced, non-functional aberrant E-cadherin
      transcript that lacks exon 11 and is over expressed in malignant cells as
      compared to the normal non-malignant cells. This increase in the aberrant
      transcript is a mechanism of loss of E-cadherin gene expression as it is rapidly
      degraded by the nonsense mediated decay pathway. To study the mechanism of this
      gene missplicing we analyzed the role of histone epigenetic modifications in lung
      cancer cell lines. The treatment of low E-cadherin lung cancer cell lines with
      histone deacetylase inhibitor (HDACi, MS-275) resulted in the preferential
      expression of the correctly spliced transcripts in the low E-cadherin expressing
      cell lines only. Chromatin immunoprecipitation (ChIP) assays revealed that the
      histone hypoacetylation levels correlate with aberrant exon 11 splicing as there
      is more aberrant splicing in cell lines with E-cadherin promoter hypoacetylation.
      Inactivation of histone deacetylases (HDAC) 1, 2 and 3 resulted in an increase in
      E-cadherin expression and an increase in the ratio of the correctly spliced E
      cadherin transcript. As transcription of the gene is closely linked to splicing,
      we considered the possibility that change in E-cadherin transcription correlates
      with splicing. The Zeb1 epithelial-mesenchymal transformation (EMT) inducer
      silences E-cadherin expression and could also alter the splicing of this exon.
      Inhibition of the E-cadherin promoter transcription with Zeb1 expression
      increases aberrant splicing and the reverse is observed when Zeb1 is knocked
      down. The role of HDAC inhibitors was also studied in vivo in a immunodeficient
      mouse xenograft model. Exposure of mice to HDACi resulted in growth inhibition,
      increase in E-cadherin expression, alteration of aberrant splicing and the
      reversal of EMT in mouse tumors. The findings support the modulation of E
      cadherin exon 11 inclusion or exclusion by histone epigenetic modifications as
      they change the overall chromatin structure. The results provide an interesting
      link between epigenetic alterations in cancer cells and gene splicing in addition
      to their effect on gene silencing. 

PMID- 23977448
TI  - Preclinical evaluation of the mTOR inhibitor, temsirolimus, in combination with
      the epothilone B analog, ixabepilone in renal cell carcinoma.
AB  - Historically, metastatic renal cell carcinoma (mRCC) is more resistant to
      conventional cytotoxic chemotherapeutic agents than other solid tumors. Although
      significant progress has been made over the last decade with several novel
      therapeutics, these agents invariably go on to fail, largely due to either
      intrinsic or acquired resistance. To help overcome, or at least delay resistance,
      combinatorial therapies utilizing agents with disparate, and ideally
      complementary, mechanisms of actions are needed. In this report, we assess the
      novel combination of the mTOR inhibitor, temsirolimus, with the microtubule
      stabilizing drug ixabepilone in RCC. Our results demonstrate synergy in multiple
      cell lines of RCC and further evaluation of this combination is warranted in the
      clinical setting. Activation of the endoplasmic reticulum (ER) stress response
      pathway may in part explain the combinatorial synergy. We further propose that ER
      stress induced proteins may serve as early response biomarkers to combinatorial
      therapy in a clinical trial. 

PMID- 23977449
TI  - Validation of esophageal squamous cell carcinoma candidate genes from high
      throughput transcriptomic studies.
AB  - In a recent study, a unique gene expression signature was observed when comparing
      esophageal squamous cell carcinoma (ESCC) epithelial cells to normal esophageal
      epithelial cells using laser capture microdissection (LCM) and cDNA microarray
      technology. To validate the expression of several intriguing genes from that
      study (KRT17, cornulin, CD44, and EpCAM), we employed two new technologies,
      expression microdissection (xMD) for high-throughput microdissection facilitating
      protein analysis and RNAscope for the evaluation of low abundant transcripts in
      situ. For protein measurements, xMD technology was utilized to specifically
      procure sufficient tumor and normal epithelium from frozen human tissue for
      immunoblot analysis of KRT17 (CK17) and cornulin. A novel in situ hybridization
      method (RNAscope) was used to determine the transcript level of two relatively
      low expressed genes, CD44 and EpCAM in both individual formalin-fixed paraffin
      embedded (FFPE) tissue sections and in an ESCC tissue microarray (TMA). The
      results successfully confirmed the initial expression pattern observed for all
      four genes, potentially implicating them in the pathogenesis of ESCC.
      Additionally, the study provides important methodological information on the
      overall process of candidate gene validation. 

PMID- 23977450
TI  - Ki67-BCL2 index in prognosis of malignant peritoneal mesothelioma.
AB  - BACKGROUND: malignant peritoneal mesothelioma (MPM) is a rare peritoneal
      mesothelial neoplasm. Ki67 and BCL2 are established prognostic markers in several
      cancers. High Ki67 expression indicates tumour progression, whilst similar
      expression of BCL2 retards tumour replication. Traditionally, prognosis in MPM is
      gauged with a single biomarker assessed separately in a dichotomous manner. Here,
      we examine prognosis with dual biomarkers incorporated in a model to predict
      survival. MATERIALS AND METHODS: Forty two MPM archival patient tumours were
      screened for Ki67 and BCL2 by immunohistochemistry and evaluated using standard
      methods. Ki67 and BCL2 expression was incorporated into a prognostic model to
      develop Ki67-BCL2 index. Using this index, three hazard groups were identified
      (high, medium and low risk). Kaplan-Meier survival analysis was performed to
      assess the significance of these hazard groups in the various clinicopathological
      categories. RESULTS: In all clinicopathological categories, high risk group
      showed poor prognosis compared to low risk group (p = < 0.001). Compared to
      medium risk, high risk group carried poor prognosis in all tumours, females,
      epitheloid tumours, peritoneal cancer index (PCI) < 20, >= 20, age at diagnosis
      (AAD) < 60, and >= 60 years. Independent of the Ki67-BCL2 index, male,
      sarcomatoid, PCI >= 20 and AAD >= 60 were poor prognostic factors. High risk
      group was an independent poor prognostic factor in all tumours, males, females
      and age < 60 years. The distribution of high risk: low risk group in male and
      female was 3: 2 and 2: 3, respectively, indicating a gender difference. Comparing
      hazard ratios generated by Ki67-BCL2 index to that of either Ki67 or BCL2, as a
      single prognostic biomarker, there was a reduction of HR values. CONCLUSION: Ki67
      BCL2 index seems to suggest a more sensitive method of predicting prognosis.
      However, the current model needs further evaluation in an independent large
      cohort sample.

PMID- 23977451
TI  - Pharmacological modulation of blood-brain barrier increases permeability of
      doxorubicin into the rat brain.
AB  - Our group recently demonstrated in a rat model that pretreatment with morphine
      facilitates doxorubicin delivery to the brain in the absence of signs of
      increased acute systemic toxicity. Morphine and other drugs such as dexamethasone
      or ondansetron seem to inhibit MDR proteins localized on blood-brain barrier,
      neurons and glial cells increasing the access of doxorubicin to the brain by
      efflux transporters competition. We explored the feasibility of active
      modification of the blood-brain barrier protection, by using morphine
      dexamethasone or ondansetron pretreatment, to allow doxorubicin accumulation into
      the brain in a rodent model. Rats were pretreated with morphine (10 mg/kg, i.p.),
      dexamethasone (2 mg/kg, i.p.) or ondansetron (2 mg/kg, i.p.) before injection of
      doxorubicin (12 mg/kg, i.p.). Quantitative analysis of doxorubicin was performed
      by mass spectrometry. Acute hearth and kidney damage was analyzed by measuring
      doxorubicin accumulation, LDH activity and malondialdehyde plasma levels. The
      concentration of doxorubicin was significantly higher in all brain areas of rats
      pretreated with morphine (P < 0.001) or ondansetron (P < 0.05) than in control
      tissues. The concentration of doxorubicin was significantly higher in cerebral
      hemispheres and brainstem (P < 0.05) but not in cerebellum of rats pretreated
      with dexamethasone than in control tissues. Pretreatment with any of these drugs
      did not increase LDH activity or lipid peroxidation compared to controls. Our
      data suggest that morphine, dexamethasone or ondansetron pretreatment is able to
      allow doxorubicin penetration inside the brain by modulating the BBB. This effect
      is not associated with acute cardiac or renal toxicity. This finding might
      provide the rationale for clinical applications in the treatment of refractory
      brain tumors and pave the way to novel applications of active but currently
      inapplicable chemotherapeutic drugs. 

PMID- 23977453
TI  - Mcl-1 as a Therapeutic Target in Acute Myelogenous Leukemia (AML).
AB  - The B-cell lymphoma-2 (Bcl-2) family of proteins regulates the intrinsic, or
      mitochondrial pathway of apoptosis, the final common mechanism of cell death in
      response to a variety of physiologic and pharmacologic signals, and plays a
      central role in AML pathogenesis, prognosis and responsiveness to chemotherapy.
      Traditionally thought to be an important survival factor for multiple myeloma
      cells, the anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1)
      has recently been shown in preclinical studies to be critical to the development
      and maintenance of AML, making it an attractive therapeutic target in this
      disease. Several characteristics, such as its very short half-life, distinguish
      Mcl-1 from other anti-apoptotic Bcl-2 family members. Additionally, Mcl-1 levels
      are regulated by a large number of pathways affecting its transcription,
      translation and degradation. A variety of approaches exploiting these features
      has been developed to inhibit directly or indirectly the anti-apoptotic function
      of Mcl-1. Many of these lend themselves well to combination therapies, leading to
      striking synergism, at least in preclinical models. In this brief review, we
      highlight some of the more promising strategies targeting Mcl-1 in AML, with a
      particular emphasis on rational combinations of novel agents.

PMID- 23977454
TI  - Strategies to circumvent the T315I gatekeeper mutation in the Bcr-Abl tyrosine
      kinase.
AB  - Despite the remarkable success of imatinib against Bcr-Abl, development of
      secondary resistance, most often due to point mutations in the Bcr-Abl tyrosine
      kinase (TK) domain, is quite common. Of these, the T315I "gatekeeper" mutation is
      resistant to all currently registered Bcr-Abl TK inhibitors (TKIs) with the
      notable exception of ponatinib (IclusigTM), which was very recently approved by
      the United States Food and Drug Administration (FDA). Besides ponatinib, numerous
      strategies have been developed to circumvent this problem. These include the
      protein synthesis inhibitor omacetaxine (Synribo(r)), and "switch-control"
      inhibitors. Dual Bcr-Abl and aurora kinase inhibitors represent another promising
      strategy. Finally, several promising synergistic combinations, such as TKIs with
      histone deacetylase inhibitors (HDACIs), warrant attention.

PMID- 23977452
TI  - Liver Injury and the Activation of the Hepatic Myofibroblasts.
AB  - Liver fibrosis is a wound healing process, the end result of chronic liver injury
      elicited by different noxious stimuli. Activated hepatic stellate cells or
      myofibroblasts and portal myofibroblasts are considered as the main producers of
      the extracellular matrix in the liver. Upon liver injury the quiescent stellate
      cells transdifferentiate into myofibroblasts a process highlighted by the loss of
      vitamin A stores, upregulation of interstitial type collagens, smooth muscle
      alpha actin, matrix metalloproteinases, proteoglycans, and the induction of cell
      survival pathways. Activation of hepatic stellate cells is a result of a complex
      interplay between the parenchymal cells, immune cells, extracellular matrix
      mechanics and extrahepatic milieu such as the gut microbiome. In this review we
      will focus on the pathomechanism of stellate cell activation following chronic
      liver injury; with the aim of identifying possible treatment targets for anti
      fibrogenic agents.

PMID- 23977456
TI  - Foreword.

PMID- 23977455
TI  - Elevated amygdala responses to emotional faces in youths with chronic
      irritability or bipolar disorder.
AB  - A major controversy in child psychiatry is whether bipolar disorder (BD) presents
      in children as severe, non-episodic irritability (operationalized here as severe
      mood dysregulation, SMD), rather than with manic episodes as in adults. Both
      classic, episodic BD and SMD are severe mood disorders characterized by deficits
      in processing emotional stimuli. Neuroimaging techniques can be used to test
      whether the pathophysiology mediating these deficits are similar across the two
      phenotypes. Amygdala dysfunction during face emotion processing is well
      documented in BD, but little is known about amygdala dysfunction in chronically
      irritable youth. We compared neural activation in SMD (n=19), BD (n=19), and
      healthy volunteer (HV; n=15) youths during an implicit face-emotion processing
      task with angry, fearful and neutral expressions. In the right amygdala, both SMD
      and BD exhibited greater activity across all expressions than HV. However, SMD
      and BD differed from each other and HV in posterior cingulate cortex, posterior
      insula, and inferior parietal lobe. In these regions, only SMD showed
      deactivation in response to fearful expressions, whereas only BD showed
      deactivation in response to angry expressions. Thus, during implicit face emotion
      processing, youth with BD and those with SMD exhibit similar amygdala dysfunction
      but different abnormalities in regions involved in information monitoring and
      integration.

PMID- 23977457
TI  - A systematic review and meta-analysis on pulmonary resections by robotic video
      assisted thoracic surgery.
AB  - BACKGROUND: Pulmonary resection by robotic video-assisted thoracic surgery
      (RVATS) has been performed for selected patients in specialized centers over the
      past decade. Despite encouraging results from case-series reports, there remains
      a lack of robust clinical evidence for this relatively novel surgical technique.
      The present systematic review aimed to assess the short- and long-term safety and
      efficacy of RVATS. METHODS: Nine relevant and updated studies were identified
      from 12 institutions using five electronic databases. Endpoints included
      perioperative morbidity and mortality, conversion rate, operative time, length of
      hospitalization, intraoperative blood loss, duration of chest drainage,
      recurrence rate and long-term survival. In addition, cost analyses and quality of
      life assessments were also systematically evaluated. Comparative outcomes were
      meta-analyzed when data were available. RESULTS: All institutions used the same
      master-slave robotic system (da Vinci, Intuitive Surgical, Sunnyvale, California)
      and most patients underwent lobectomies for early-stage non-small cell lung
      cancers. Perioperative mortality rates for patients who underwent pulmonary
      resection by RVATS ranged from 0-3.8%, whilst overall morbidity rates ranged from
      10-39%. Two propensity-score analyses compared patients with malignant disease
      who underwent pulmonary resection by RVATS or thoracotomy, and a meta-analysis
      was performed to identify a trend towards fewer complications after RVATS. In
      addition, one cost analysis and one quality of life study reported improved
      outcomes for RVATS when compared to open thoracotomy. CONCLUSIONS: Results of the
      present systematic review suggest that RVATS is feasible and can be performed
      safely for selected patients in specialized centers. Perioperative outcomes
      including postoperative complications were similar to historical accounts of
      conventional VATS. A steep learning curve for RVATS was identified in a number of
      institutional reports, which was most evident in the first 20 cases. Future
      studies should aim to present data with longer follow-up, clearly defined
      surgical outcomes, and through an intention-to-treat analysis.

PMID- 23977458
TI  - Video-assisted thoracoscopic pulmonary resections - The Melbourne experience.
AB  - BACKGROUND: Despite its privileged economic and educational place in the world,
      Melbourne was relatively slow to embrace video-assisted thoracic surgery (VATS)
      for lobectomy. The initial driver of this was Professor C Peter Clarke at the
      Austin Hospital at the beginning of the new millennium. His legacy was carried on
      by his apprentice, but at St Vincent's Hospital. After a period of slow
      development, it became the procedure of choice from 2005, and began to filter
      sporadically to other hospitals from 2010. METHODS: This paper details the
      historical development, techniques and results of 343 VATS pulmonary resections
      (including lobectomies, sub-lobar anatomical resections, sleeve resections, bi
      lobectomies and pneumonectomies). RESULTS: In-hospital and 30-day mortality was
      2.0% and 5-year survival for all stages of NSCLC was 70%. Over 36% of patients
      were stage II-III using the new 7(th) revision TNM staging system. The conversion
      to thoracotomy rate was 4.7%. The estimated learning curve for this experience
      VATS lobectomy appears to be in the range of 15-20 cases. In this series, the
      same lymph node dissection or sampling was attempted and usually achieved as
      would have occurred at thoracotomy. CONCLUSIONS: The results confirm the findings
      of other large case series that the benefits of a minimally invasive approach are
      achieved without compromising the long-term survival.

PMID- 23977459
TI  - A meta-analysis of unmatched and matched patients comparing video-assisted
      thoracoscopic lobectomy and conventional open lobectomy.
AB  - BACKGROUND: Video-assisted thoracic surgery (VATS) for patients with early-stage
      non-small cell lung cancer (NSCLC) has been established as a safe and feasible
      alternative to open thoracotomy. This meta-analysis aims to assess the potential
      difference between unmatched and propensity score-matched cohorts who underwent
      VATS versus open thoracotomy in the current literature. METHODS: Three relevant
      studies with unmatched and propensity score-matched patients were identified from
      six electronic databases to examine perioperative outcomes after VATS lobectomy
      versus open thoracotomy for patients with early-stage NSCLC. Endpoints included
      perioperative mortality and morbidity, individual postoperative complications and
      duration of hospitalization. RESULTS: Results indicate that perioperative
      mortality was significantly lower for VATS compared to open thoracotomy in
      unmatched patients but no significant difference was detected amongst propensity
      score-matched patients. Similarly, the incidences of prolonged air leak and
      sepsis were significantly lower for VATS in the unmatched cohort, but not
      identified in the propensity score-matched cohort. In both the unmatched and
      matched groups, patients who underwent VATS were found to have a significantly
      lower overall perioperative morbidity rate, incidences of pneumonia and atrial
      arrhythmias, and a shorter duration of hospitalization in comparison to patients
      who underwent open thoracotomy. CONCLUSIONS: The present meta-analysis indicates
      that VATS lobectomy has superior perioperative outcomes compared to open
      thoracotomy in both matched and unmatched cohorts. However, the extent of the
      superiority may have been overestimated in the unmatched patients when compared
      to propensity score-matched patients. Due to the limited number of studies with
      available data included in the present meta-analysis, these results are only of
      observational interest and should be interpreted with caution.

PMID- 23977460
TI  - Robotic lobectomy for non-small cell lung cancer (NSCLC): Multi-center registry
      study of long-term oncologic results.

PMID- 23977461
TI  - Efficacy of mediastinal lymph node dissection during thoracoscopic lobectomy.

PMID- 23977462
TI  - Training in video-assisted thoracoscopic lobectomy.

PMID- 23977463
TI  - Video-assisted thoracoscopic surgery (VATS) for locally advanced lung cancer.

PMID- 23977464
TI  - How to set up a VATS lobectomy program.

PMID- 23977465
TI  - Learning curve associated with VATS lobectomy.

PMID- 23977466
TI  - VATS lobectomy lymph node management.

PMID- 23977467
TI  - Cost concerns for robotic thoracic surgery.

PMID- 23977468
TI  - Perspectives on robotic pulmonary resection: It's current and future status.

PMID- 23977469
TI  - Video-assisted thoracoscopic lobectomy: the Edinburgh posterior approach.

PMID- 23977470
TI  - Video-assisted thoracoscopic lobectomy using a standardized three-port anterior
      approach - The Copenhagen experience.

PMID- 23977471
TI  - Robotic-assisted pulmonary resection - Right upper lobectomy.

PMID- 23977472
TI  - Video-atlas of thoracoscopic formal lung resections emulating traditional open
      techniques - Editor's comments.

PMID- 23977473
TI  - Video-atlas of thoracoscopic formal lung resections emulating traditional open
      techniques.

PMID- 23977474
TI  - A complete video-atlas of five robotic-assisted lobectomies.

PMID- 23977475
TI  - VATS lymph node dissection.

PMID- 23977476
TI  - A video-atlas of video-assisted thoracoscopic lobectomy using a standardized
      three-port anterior approach.

PMID- 23977477
TI  - Video-assisted thoracoscopic pneumonectomy: the Edinburgh posterior approach.

PMID- 23977478
TI  - Pulmonary artery bleeding caused during VATS lobectomy.

PMID- 23977479
TI  - Troublesome bleeding at mediastinoscopy.

PMID- 23977480
TI  - Minimally invasive pulmonary resection.

PMID- 23977481
TI  - Transapical aortic valve implantation - A paradigm for innovation and
      collaboration in modern cardiac surgery.

PMID- 23977482
TI  - A systematic review of transapical aortic valve implantation.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) through a transapical
      approach (TAAVI) for severe aortic stenosis becomes the procedure of choice in
      cases where patients have peripheral artery disease and unfeasible access due to
      excessive atherosclerotic disease of the iliofemoral vessels and aorta. The
      present systematic review aimed to assess the safety, success rate, clinical
      outcomes, hemodynamic outcomes, and survival benefits of TAAVI. METHODS:
      Electronic searches were performed in 6 databases from January 2000 to February
      2012. The primary end points included feasibility and safety. Other end points
      included echocardiographic findings, functional class improvement, and survival.
      RESULTS: After applying the inclusion and exclusion criteria, 48 out of 154
      shortlisted potentially relevant articles were selected for assessment. Of these,
      26 studies from 24 centers including total number of 2,807 patients were included
      for appraisal and data extraction. The current evidence on TAAVI for aortic
      stenosis is limited to observational studies. Successful TAAVI implantation
      occurred in >90% of patients. On average, the procedure took between 64 to 154
      minutes to complete. The incidence of major adverse events included 30-day
      mortality (4.7-20.8%); cerebrovascular accident (0-16.3%); major tachyarrhythmia
      (0-48.8%); bradyarrhythmia requiring permanent pacemaker insertion (0-18.7%);
      cardiac tamponade (0-11%); major bleeding (1-17%); myocardial infarction (0-6%);
      aortic dissection/rupture (0-5%); moderate to severe paravalvular leak (0.7-24%);
      cardiopulmonary bypass support (0-15%); conversion to surgery (0-9.5%); and valve
      in-valve implantation (0.6-8%). Mean aortic valve area improved from 0.4-0.7
      cm(2) before TAAVI to 1.4-2.1 cm(2) after TAAVI. The peak pressure gradient
      across the aortic valve decreased from >70 mmHg to <20 mmHg after TAAVI. One-year
      survival ranged from 49.3% to 82% and the 3-year survival was 58% in 2 series.
      CONCLUSIONS: TAAVI appears to be feasible with a reasonable safety and efficacy
      portfolio. Randomised controlled trials are required to compare transapical vs.
      transfemoral TAVI when both techniques are equally feasible.

PMID- 23977483
TI  - Transapical aortic valve implantation - The Leipzig experience.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) represents a
      significant development in the treatment of high risk patients with aortic
      stenosis. As one of the first centers to perform transapical TAVI (taTAVI), we
      herein review our five-year experience with this technique. METHODS: All patients
      undergoing taTAVI with an Edwards Sapien valve at the Leipzig Heart Center
      between 2006 and 2011 (n=439) were analysed. Data was drawn from a prospective
      database and retrospectively analysed. The learning curve was reviewed by means
      of descriptive statistics as well as cumulative sum failure analysis (CUSUM). All
      results are presented in compliance with Valve Academic Research Consortium
      (VARC) criteria. RESULTS: The mean patient age was 81.5+/-6.4 years and 64.0%
      were female. The mean logistic EuroSCORE and STS risk of mortality were 29.7%+/
      15.7% and 11.4%+/-7.6%, respectively. Procedural success was 90.2%. Stroke
      occurred in 2.1% of patients intra-operatively and a further 2.1% suffered stroke
      during their hospital stay. Mean transvalvular gradient was 9.0+/-3.9 mmHg and
      effective valve orifice area 1.3+/-0.6 cm(2). Moderate or greater aortic
      insufficiency was present in 5.7% of patients and remained stable during follow
      up. Overall survival was 90% at 30 days, 73% at 1 year, 68% at 2 years, 58% at 3
      years, 53% at 4 years, and 44% at 5 years. CUSUM analysis revealed a definitive
      learning curve regarding the occurrence of major complications, with a
      progressive improvement after the initial 150 cases. CONCLUSION: TaTAVI has
      become a routine approach for high risk patients with symptomatic severe aortic
      stenosis. Although taTAVI is a safe procedure with reproducible results, future
      research should focus on methods of reducing known complications and the
      associated learning curve for this procedure.

PMID- 23977484
TI  - Transapical aortic valve implantation: The Vancouver experience.
AB  - INTRODUCTION: Off-pump transapical aortic valve implantation (TA-TAVI) through
      mini-thoracotomy was first performed in Vancouver, Canada in October 2005. The
      objective of this manuscript is to describe the Vancouver experience with 178 TA
      TAVI cases in symptomatic severe aortic stenosis (AS) since 2005. METHODS:
      Baseline characteristics and in-hospital outcomes were calculated for the overall
      cohort. To compare pre-procedure and post-procedure echocardiographic
      measurements, one way analysis of variance was utilized, followed by Tukey's HSD.
      In-hospital outcomes were compared between early and late cohorts using Z-test
      and chi-squared test as appropriate. Kaplan-Meier analysis was used to generate 3
      year survival curves. The Log-rank test was used to compare survival between low
      risk and high-risk groups, based on STS score. RESULTS: Between October 2005
      March 2012, TA-TAVI was performed in 178 patients. Mean age was 80.5+/-8.6 years.
      Congestive heart failure and renal failure were more common in the late cohort,
      while previous myocardial infarction was more common in the early cohort
      (P<0.05). Eleven patients (6.2%) had significant intra-operative complications,
      including death (1.7%), conversion to CPB (3.9%), and valve embolization (1.1%).
      In-hospital survival was 87.9%. Mean length of hospital stay was 12.2+/-17.1
      days. In-hospital incidence of stroke was 3.4%. Bleeding (20.2% vs. 4.7%) and
      vascular (14.6% vs. 3.5%) complications were more common in the early cohort.
      Echocardiography demonstrated a significant increase in aortic valve area and
      decrease in mean transvalvular gradient post-procedure. These improvements were
      maintained throughout the 3-year follow-up period. Overall survival was 72.1% at
      6 months, 67.7% at 12 months, 55.5% at 24 months, and 47.3% at 36 months.
      Repeated Kaplan-Meier analysis for the 2 groups stratified by STS score,
      demonstrated improved survival in the low-risk group (Log-rank P=0.039).
      CONCLUSIONS: Among patients with symptomatic severe AS at high risk for
      conventional AVR, TA-TAVI is a reasonable therapeutic option with acceptable
      risk. Long-term survival appears to be superior in lower-risk patients.

PMID- 23977485
TI  - Perspective on the cost-effectiveness of transapical aortic valve implantation in
      high-risk patients: Outcomes of a decision-analytic model.
AB  - BACKGROUND: The incremental cost-effectiveness of transapical transcatheter
      aortic valve implantation (TAVI) is ill-defined in high-risk patients where
      aortic valve replacement (AVR) is an option, and has not been ascertained outside
      a randomized controlled trial. METHODS: We developed a Markov model to examine
      the progression of patients between health states, defined as peri- and post
      procedural, post-complication, and death. The mean and variance of risks,
      transition probabilities, utilities and cost of transapical TAVI, high-risk AVR,
      and medical management were derived from analysis of relevant registries. Outcome
      and cost were derived from 10,000 simulations. Sensitivity analyses further
      evaluated the impact of mortality, stroke, and other commonly observed outcomes.
      RESULTS: In the reference case, both transapical TAVI and high-risk AVR and TAVI
      were cost-effective when compared to medical management ($44,384/QALY and
      $42,637/QALY, respectively). Transapical TAVI failed to meet accepted criteria
      for incremental cost-effectiveness relative to AVR, which was the dominant
      strategy. In sensitivity analyses, the mortality rates related to the two
      strategies, the utilities post-AVR and post-transapical TAVI, and the cost of
      transapical TAVI, were the main drivers of model outcome. CONCLUSION: Transapical
      TAVI did not satisfy current metrics of incremental cost-effectiveness relative
      to high-risk AVR in the reference case. However, it may provide net health
      benefits at acceptable cost in selected high-risk patients among whom AVR is the
      standard intervention.

PMID- 23977486
TI  - Aortic valve calcium scoring is a predictor of paravalvular aortic regurgitation
      after transcatheter aortic valve implantation.

PMID- 23977487
TI  - Aortic valve calcium load before TAVI: Is it important?

PMID- 23977488
TI  - The learning curve associated with transapical aortic valve implantation.

PMID- 23977489
TI  - Patient-prosthesis mismatch after transapical aortic valve implantation.

PMID- 23977490
TI  - Transapical aortic valve implantation with anatomically oriented prostheses.

PMID- 23977491
TI  - 3-year outcomes of self-expanding Corevalve prosthesis - The Italian Registry.

PMID- 23977492
TI  - How to set up a successful TAVI program.

PMID- 23977493
TI  - Is proctoring mandatory when starting a TAVI program?

PMID- 23977494
TI  - Aortic valve replacement vs. transcatheter aortic valve implantation: Patient
      selection.

PMID- 23977495
TI  - Transcatheter aortic valve implantation: The transfemoral versus the transapical
      approach.

PMID- 23977497
TI  - Transapical vs. transfemoral aortic valve implantation: Which approach for which
      patient, from a surgeon's standpoint.

PMID- 23977496
TI  - Patient selection for transcatheter aortic valve implantation: An interventional
      cardiology perspective.
AB  - Transcatheter aortic valve implantation (TAVI) has emerged as a highly effective
      minimally invasive treatment symptomatic for severe calcific aortic stenosis in
      patients at high or prohibitive surgical risk. The success of TAVI has been
      determined by a number of factors, but in particular by appropriate patient
      selection. Appropriate patient selection involves identifying patients with the
      potential to benefit most from TAVI and individualizing the bioprosthesis type
      and size, and the vascular access site for each case. We present herein, our
      critical appraisal on patient selection for TAVI: an interventional cardiology
      perspective. 

PMID- 23977498
TI  - The versatility of transapical access: Will it lead to a completely new approach
      to valvular therapy?

PMID- 23977500
TI  - Illustrated techniques for transapical aortic valve implantation.

PMID- 23977499
TI  - Transcatheter resection of the native aortic valve prior to endovalve
      implantation - A rational approach to reduce TAVI-induced complications.

PMID- 23977501
TI  - Video-atlas of transapical aortic valve implantation.

PMID- 23977502
TI  - Migration of the transcatheter valve into the left ventricle.

PMID- 23977503
TI  - Sizing the aortic annulus.
AB  - Transcatheter aortic valve implantation (TAVI) is a valuable alternative for
      aortic valve replacement in selected high-risk candidates. Accurate preoperative
      assessment of the aortic annular dimensions is crucial for the success of TAVI,
      since choice of an incorrectly sized prosthesis may result in catastrophic
      complications. These complications include annular rupture and coronary arterial
      obstruction, if the prosthesis is too big, or prosthesis migration and severe
      paravalvular leakage, if the prosthesis is too small. According to current
      recommendations, the choice of prosthesis size is based on transoesophageal
      echocardiography (TEE) measurements. However, TEE results are dependent on
      operator experience. Moreover, recent research has shown that TEE can
      significantly underestimate annular dimensional measurements. Alternative sizing
      methods based on Multidetector Computed Tomography (MDCT) or manometry during
      balloon aortic valvuloplasty have therefore been developed. We present a brief
      overview of the imaging modalities available for preoperative assessment of
      annular size and discuss their potential advantages and limitations. 

PMID- 23977504
TI  - Transapical aortic valve implantation in the presence of a mitral prosthesis.

PMID- 23977506
TI  - TAVI: Transcatheter Aortic Valve Implantation.

PMID- 23977505
TI  - Transcatheter aortic "valve-in-valve" for degenerated bioprostheses: Choosing the
      right TAVI valve.
AB  - Bioprosthetic aortic valve replacement is the treatment of choice for patients
      over 65 years of age suffering from aortic valve disease, and for younger
      patients with contraindications to long-lasting anticoagulation. Despite several
      technical improvements to reduce the risk of structural valve degeneration (SVD),
      the risk of SVD still exists, in particular for hemodialysis patients and
      patients under 60 years of age at surgery. Redo open heart surgery is the
      treatment of choice in case of valve degeneration, but caries a higher surgical
      risk when elderly patients with comorbidities are concerned. In the last 5 years,
      transcatheter aortic "valve-in-valve" procedures represent a valid alternative to
      standard redo surgery in selected patients. Valve-in-valve procedures represent a
      less invasive approach in high-risk patients and the published results are very
      encouraging. Technical success rates of 100% have been reported, as have the
      absence of paravalvular leaks, acceptable trans-valvular gradients (depending on
      the size of the original bioprosthesis), and low complication rates. The current
      article focuses on choosing the correct transcutaneous valve to match the
      patient's existing bioprosthesis for valve-in-valve procedures. 

PMID- 23977507
TI  - New approaches to an old problem.

PMID- 23977508
TI  - Combined open and endovascular treatment of thoracoabdominal aortic pathologies:
      a systematic review and meta-analysis.
AB  - BACKGROUND: A combined open-endovascular technique has emerged as an alternative
      treatment option for thoracoabdominal pathologies. However, reported experiences
      from various medical centers have been contradictory and heterogeneous. The aim
      of this study is to assess the mortality rate and various complication rates
      associated with this approach. METHODS: An electronic health database search was
      performed on all articles published up to March of 2012 describing combined open
      endovascular repair of thoracoabdominal pathologies. Studies were included in the
      meta-analysis if they had >=10 patients and reported the basic outcome criteria.
      End points of the meta-analysis were defined as primary technical success,
      endoprosthesis related complications, 30-day/in-hospital mortality, symptoms of
      spinal cord ischemia (SCI) and irreversible paraplegia, permanent renal function
      impairment, and other major complications. RESULTS: Fourteen studies were deemed
      eligible for this meta-analysis with a total of 528 patients (68.0% male, mean
      age 70.5 years). The mean follow-up period was 34.2 months. The pooled estimate
      for primary technical success and visceral graft patency was 95.4% and 96.5%
      respectively. An endoleak developed in 106 (21.1%) patients in whom both stages
      had been completed. The pooled rate for symptomatic SCI was 7.0% and for
      irreversible paraplegia 4.4%. The pooled proportion for permanent renal failure
      was 7.0% and for mesenteric ischemia 4.5%. Prolonged respiratory support and
      cardiac complications were observed in a pooled rate of 7.8% and 4.6%
      respectively. The meta-analysis for 30-day/in-hospital mortality revealed a
      pooled rate of 14.3%. CONCLUSIONS: Although the hybrid technique for
      thoracoabdominal aortic pathology provides a less invasive approach, the
      technique is still associated with a considerable morbidity and mortality rates.
      High risk patients unfit to withstand open repair, are equally likely to suffer
      significant complications with the hybrid procedure. The choice of the optimal
      treatment strategy for thoracoabdominal pathologies should be carefully made on a
      patient to patient basis, assessing the clinical fitness and the anatomical
      suitability of each patient. The hybrid approach should be reserved for high
      volume centers with accumulated experience and high standards of perioperative
      management.

PMID- 23977509
TI  - Thoracoabdominal aortic aneurysm.

PMID- 23977510
TI  - Results of open thoracoabdominal aortic aneurysm repair.
AB  - BACKGROUND: Open surgical repair of thoracoabdominal aortic aneurysms (TAAAs)
      enables the effective replacement of the diseased aortic segment and reliably
      prevents aneurysm rupture. However, these operations also carry substantial risk
      of perioperative morbidity and mortality, principally caused by the associated
      ischemic insult involving the spinal cord, kidneys, and other abdominal viscera.
      Here, we describe the early outcomes of a contemporary series of open TAAA
      repairs. METHODS: We reviewed the outcomes of 823 open TAAA repairs performed
      between January 2005 and May 2012. Of these, 209 (25.4%) were Crawford extent I
      repairs, 264 (32.1%) were extent II, 157 (19.1%) were extent III, and 193 (23.5%)
      were extent IV. Aortic dissection was present in 350 (42.5%) cases, and aneurysm
      rupture was present in 37 (4.5%). Adjuncts used during the procedures included
      cerebrospinal fluid drainage in 639 (77.6%) cases, left heart bypass in 430
      (52.2%), and cold renal perfusion in 674 (81.9%). RESULTS: The composite
      endpoint, adverse outcome-defined as operative death, renal failure that
      necessitated dialysis at discharge, stroke, or permanent paraplegia or
      paraparesis-occurred after 131 (15.9%) procedures. There were 69 (8.4%) operative
      deaths. Permanent paraplegia or paraparesis occurred after 42 (5.1%) cases,
      stroke occurred after 27 (3.3%), and renal failure necessitating permanent
      dialysis occurred after 45 (5.5%). CONCLUSIONS: Although open surgical repair of
      the thoracoabdominal aorta can be life-saving to patients at risk for fatal
      aneurysm rupture, these operations remain challenging and are associated with
      substantial risk of early death and major complications. Additional improvements
      are needed to further reduce the risks associated with TAAA repair, particularly
      as increasing numbers of patients with advanced age and multiple or severe
      comorbidities present for treatment.

PMID- 23977511
TI  - Clinical outcomes of hybrid repair for thoracoabdominal aortic aneurysms.
AB  - BACKGROUND: Thoracoabdominal aortic aneurysm (TAAA) hybrid repair consists of
      aortic visceral branch rerouting followed by TAAA endograft exclusion. This
      technique has been shown to represent a technically feasible strategy in selected
      patients. METHODS: We analyzed 52 high-risk patients who underwent hybrid TAAA
      repair between 2001 and 2012 in our centre with a variety of visceral rerouting
      configurations and of commercially available thoracic endografts. Thirty-seven
      simultaneous (71.2%) and 15 staged procedures (21.8%) were performed with a four
      vessel revascularization in 18 cases (34.6%), a three-vessel revascularization in
      11 cases (21.2%) and a two-vessel revascularization in 23 cases (44.2%). RESULTS:
      No intraoperative deaths were observed. We recorded a perioperative mortality
      rate of 13.5% (n=7), including deaths from multiorgan failure (n=2), myocardial
      infarction (n=2), coagulopathy (n=1), pancreatitis (n=1) and bowel infarction
      (n=1). Perioperative morbidity rate was 28.8% (n=15), including 2 cases of
      transient paraparesis and 1 case of permanent paraplegia. Renal failure (n=5),
      pancreatitis (n=3), respiratory failure (n=3) and dysphagia (n=1) were also
      observed. At median follow-up of 23.9 months procedure-related mortality rate was
      9.6%: two patients died from visceral graft occlusion and three from aortic
      rupture. There were three endoleaks and one endograft migration, none of which
      resulted in death. Five patients (9.6%) died as a consequence of unrelated
      events. CONCLUSIONS: Typical complications of conventional TAAA open surgery have
      not been eliminated by hybrid repair, and significant mortality and morbidity
      rates have been recorded. Fate of visceral bypasses and incidence of endoleak and
      other endograft-related complications needs to be carefully assessed. Hybrid TAAA
      repair should currently be limited to high-risk surgical patients with unfit
      anatomy for endovascular repair.

PMID- 23977512
TI  - Endovascular repair of thoracoabdominal aneurysms: results of the first 48 cases.
AB  - BACKGROUND: In 2006, we began our experience with a novel technology for fully
      endovascular thoracoabdominal aneurysm repair, based on a custom-made, branched
      stent graft design. After 48 cases, we have learned and achieved substantial
      progress both in technical and in clinical skills. This paper describes the
      partial results of this ongoing experience. METHODS: Patients in this series were
      selected for the presence of thoracoabdominal aortic aneurysms, with or without
      dissection, which was present in one patient. The observation of extensive
      anatomical variations in several patients prompted changes in many of the basic
      stent graft configurations, which are also described. RESULTS: Between August
      2006 and June 2012, 48 patients were treated consecutively with custom-made
      branch stent grafts. The five patients with the longest follow-up available so
      far are at 71, 65, 60, 54 and 51 months post-procedure. The operative mortality
      rate, defined as death during or within a month of surgical hospitalization, was
      21% (10 patients); each case is described herein. During postoperative follow up,
      nine patients died from causes not directly related to aneurysmal disease, at 3,
      18, 20, 22, 24, 24, 37, 44 and 46 months. The main causes of death were
      myocardial infarction (four cases), cancer (two cases), gastrointestinal
      hemorrhage (one case), ischemic stroke (one case), and sepsis (one case).
      Permanent paraplegia occurred in one patient. CONCLUSIONS: It is still too soon
      to compare the results of endovascular repair of thoracoabdominal aneurysms with
      those of open surgical series. Despite the active and rapid progress currently
      observed for the endovascular method, it is still far from reaching its state-of
      the-art plateau or becoming a gold standard. Further technological and technical
      advances in endovascular stent grafting seem to have a clear potential to provide
      very satisfactory operative outcomes for thoracoabdominal aortic aneurysms.

PMID- 23977513
TI  - Thoracoabdominal aortic aneurysm: hybrid repair outcomes.
AB  - BACKGROUND: Thoracoabdominal aortic aneurysms (TAAA) remain amongst the most
      formidable of surgical challenges, particularly degenerative aneurysms in the
      elderly population with concomitant pulmonary disease. This report presents an
      update of our robust single-institution experience with "hybrid" TAAA repair
      including complete visceral debranching and endovascular aneurysm exclusion in
      high-risk patients. METHODS: Between March 2005 and June 2012, 58 patients
      underwent extra-anatomic debranching of all visceral vessels followed by aneurysm
      exclusion via endovascular means at a single institution. The median number of
      visceral vessels bypassed was 4. The debranching and endovascular portions of the
      procedure were performed as a single stage in the initial 33 patients and as a
      staged approach in the most recent n=25 cases. RESULTS: Median patient age was
      69.0 years; 50% were female. All had significant co-morbidity and were considered
      suboptimal candidates for conventional open surgical repair. Mean aortic diameter
      was 6.7!A1.2 cm. Thirty-day/in-hospital rates of death, stroke, and permanent
      paraparesis/paraplegia were 9%, 0%, and 4%, respectively; in the most recent 25
      patients undergoing staged repair these rates were 4%, 0%, and 0%. Over a mean
      follow-up of 26!A21 months, visceral graft patency is 95.3%; all occluded limbs
      were to renal vessels and none resulted in permanent dialysis. Two patients (3%)
      have required re-intervention, one for type Ib and one for type III endoleak.
      Five-year freedom from re-intervention was 94%. Kaplan-Meier overall survival was
      78% at 1 year and 62% at 5 years, with a 5-year aorta-specific survival of 87%.
      CONCLUSIONS: These updated results continue to support hybrid TAAA repair via
      complete visceral debranching and endovascular aneurysm exclusion as a good
      option for elderly high-risk patients less suited to conventional open repair. A
      staged approach to debranching and endovascular aneurysm exclusion appears to
      yield optimal results.

PMID- 23977514
TI  - Open surgical repair of thoracoabdominal aneurysms - the Massachusetts General
      Hospital experience.

PMID- 23977515
TI  - Staged approach for spinal cord protection in hybrid thoracoabdominal aortic
      aneurysm repair.

PMID- 23977516
TI  - Deep versus mild hypothermia during thoracoabdominal aortic surgery.

PMID- 23977517
TI  - Best surgical option for thoracoabdominal aneurysm repair - the open approach.

PMID- 23977518
TI  - Best surgical option for thoracoabdominal aneurysm repair - the hybrid approach.

PMID- 23977519
TI  - Best surgical option for thoracoabdominal aneurysm repair - the endovascular
      approach.

PMID- 23977520
TI  - The anatomy of the spinal cord collateral circulation.

PMID- 23977521
TI  - Patient selection for open thoracoabdominal aneurysm repair.

PMID- 23977522
TI  - Paraplegia after thoracoabdominal aortic surgery: not just assisted circulation,
      hypothermic arrest, clamp and sew, or TEVAR.

PMID- 23977523
TI  - Open reconstruction of thoracoabdominal aortic aneurysms.
AB  - Technical details of our strategy for reconstructing the thoracoabdominal aorta
      are presented. Between October 1999 and June 2012, 152 patients underwent surgery
      for thoracoabdominal aortic aneurysms (Crawford classification type I =21, type
      II =43, type III =73, type IV =15). Mean age was 64.6+/-13.9 years. Sixty-three
      (41.4%) patients had aortic dissection, including acute type B dissection in 2
      (1.2%) and ruptured aneurysms in 17 (11.2%). Eight (5.3%) patients had mycotic
      aneurysms, and 3 (2.0%) had aortitis. Emergent or urgent surgery was performed in
      25 (16.4%) patients. Preoperative computed tomography (CT) scan or magnetic
      resonance (MR) angiography detected the Adamkiewicz artery in 103 (67.8%)
      patients. Cerebrospinal fluid drainage (CSFD) was performed in 115 (75.7%)
      patients and intraoperative motor evoked potentials were recorded in 97 (63.8%).
      One hundred and seven (70.4%) patients had reconstruction of the intercostal
      arteries from T7 to L2, 35 of which were reconstructed with the aortic patch
      technique and 72 with branched grafts. The mean number of reconstructed
      intercostal arteries was 3.1+/-2.5 pairs. Mild hypothermic partial
      cardiopulmonary bypass at 32-34  degrees C was used in 105 (69.1%) patients, left
      heart bypass was used in 4 (2.6%), and deep hypothermic cardiopulmonary bypass
      below 20  degrees C was used in 42 (27.6%). Thirty-day mortality was 9 (5.9%),
      and hospital mortality was 20 (13.2%). Independent risk factors for hospital
      mortality were emergency surgery (OR 13.4, P=0.003) and aortic cross clamping
      over 2 hours (OR 5.7, P=0.04). Postoperative spinal cord ischemia occurred in 16
      (10.5%, 8 patients with paraplegia and 8 with paraparesis). Risk factors for
      developing spinal cord ischemic complications were prior surgery involving either
      the descending thoracic or the abdominal aorta (OR 3.75, P=0.05), diabetes
      mellitus (OR 5.49, P=0.03), and post-bypass hypotension <80 mmHg (OR 1.06,
      P=0.03). Postoperative survival at 5 years was 83.6+/-4.5%; 5-year survival was
      47.5+/-8.6% in patients with spinal cord ischemia and 88.9+/-10.4% in those
      without spinal cord ischemia. 

PMID- 23977524
TI  - Thoracoabdominal aortic aneurysm repair with a branched graft.

PMID- 23977525
TI  - Extent II repair of thoracoabdominal aortic aneurysm secondary to chronic
      dissection.

PMID- 23977526
TI  - Video-atlas of open thoracoabdominal aortic aneurysm repair.
AB  - Open surgical repair of thoracoabdominal aortic aneurysms has evolved
      significantly over the last decades thanks to technical improvements, especially
      in the area of organ protection. However, despite adjunctive strategies,
      morbidity and mortality rates are still not negligible. Repair of the
      thoracoabdominal aorta represents a formidable challenge for surgeons,
      anesthesiologists and patients alike. While operative repair is generally carried
      out in specialized institutions, knowledge of the state-of-the-art diagnostic,
      anesthesiologic, surgical and endovascular aspects will certainly be of great
      value to all physicians involved in the care of these patients at any level. This
      "How to" video will explain all of these diagnostic, anesthesiologic and surgical
      aspects in our daily practice. 

PMID- 23977527
TI  - Video-atlas of hybrid thoracoabdominal aortic aneurysm repair.
AB  - Although open surgical repair of thoracoabdominal aortic aneurysm (TAAA) has
      evolved significantly over the last few decades, technical challenges and current
      morbidity and mortality of the inclusion technique are still significant,
      particularly in patients with extensive aneurysms or prior aortic surgery and in
      poor surgical candidates. Hybrid TAAA repair is an appealing technique and may
      represent a "bridge" solution as we wait for larger series and reproducible
      results from the evolving experience with total endovascular TAAA repair with
      fenestrated and branched endografts. 

PMID- 23977528
TI  - Thoracoabdominal aortic aneurysm: a totally endovascular approach with a branched
      stent-graft.
AB  - This video depicts a step-by-step description of a totally endovascular approach
      to treat a patient with thoracoabdominal aneurysm, using a branched stent-graft
      system. We compare the pre and post-operative computerized tomography and show 3D
      illustrations and real-life images of the technique. 

PMID- 23977529
TI  - Thoracoabdominal aortic aneurysm repair using hypothermic cardiopulmonary bypass
      and circulatory arrest.

PMID- 23977530
TI  - Think differently: trans-apical platform for TEVAR.

PMID- 23977532
TI  - Thoracoabdominal aortic aneurysm repair.

PMID- 23977531
TI  - Mycotic thoracoabdominal aneurysms.

PMID- 23977533
TI  - Systematic review of trimodality therapy for patients with malignant pleural
      mesothelioma.
AB  - BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive form of cancer
      arising from the pleural mesothelium. Trimodality therapy (TMT) involving
      extrapleural pneumonectomy with neoadjuvant or adjuvant chemotherapy and adjuvant
      radiotherapy is a recognized treatment option with a curative intent. Despite
      encouraging results from institutional studies, TMT in the treatment of MPM
      remains controversial. The present systematic review aims to assess the safety
      and efficacy of TMT in the current literature. METHODS: A systematic review was
      performed using five electronic databases from 1 January 1985 to 1 October 2012.
      Studies were selected independently by two reviewers according to predefined
      selection criteria. The primary endpoint was overall survival. Secondary
      endpoints included disease-free survival, disease recurrence, perioperative
      morbidity and length of stay. RESULTS: Sixteen studies were included for
      quantitative assessment, including one randomized controlled trial and five
      prospective series. Median overall survival ranged from 12.8-46.9 months. Disease
      free survival ranged from 10-16.3 months. Perioperative mortality ranged from 0
      12.5%. Overall perioperative morbidity ranged from 50-82.6% and the average
      length of stay was 9-14 days. CONCLUSIONS: Outcomes of patients who underwent TMT
      in the current literature appeared to be inconsistent. Four prospective series
      involving a standardised treatment regimen with neoadjuvant chemotherapy
      indicated encouraging results based on intention-to-treat analysis. However, a
      small study assessing the feasibility of conducting a randomized controlled trial
      for TMT versus conservative treatment reported poor short- and long-term outcomes
      for patients who underwent pneumonectomy. Overall, results of the present
      systematic review suggest TMT may offer acceptable perioperative outcomes and
      long-term survival in selected patients treated in specialized centers.

PMID- 23977534
TI  - Do we need a revised staging system for malignant pleural mesothelioma? Analysis
      of the IASLC database.
AB  - INTRODUCTION: A number of staging systems have been proposed for malignant
      pleural mesothelioma (MPM) in the past, but few have utilized a TNM (tumor, node,
      metastasis) system. The International Association for the Study of Lung Cancer
      (IASLC) and the International Mesothelioma Interest Group (IMIG) previously
      developed a TNM-staging system which has been accepted by the International Union
      Against Cancer (UICC) and the American Joint Commission on Cancer (AJCC). The
      present study examines this staging system by analysing the updated IASLC
      database for patients with MPM. METHODS: De-identified data from participating
      centres dated from 1995 to 2009 were submitted to the IASLC Statistical Center.
      Surgical procedures included those with a curative or palliative intent. Survival
      was measured from the date of pathologic diagnosis to the most recent contact or
      death. Endpoints included overall survival and analysis of potential prognostic
      factors. RESULTS: Data was available for 3,101 patients from 15 centers, mostly
      from North America and Europe. After a median follow-up of 15 months, a number of
      clinicopathological and treatment-related prognostic factors were found to
      significantly influence overall survival. These included overall tumor stage
      based on the proposed TNM staging system, T category, N category, tumor
      histology, gender, age, and type of operation. CONCLUSIONS: The IASLC database
      represents the largest, multicenter and international database on MPM to date.
      Analyses demonstrate that the proposed TNM staging system effectively
      distinguishes the T and N categories, but also highlight areas for potential
      revision in the future.

PMID- 23977535
TI  - Biomarkers and prognostic factors for mesothelioma.

PMID- 23977536
TI  - Novel radiation therapy approaches in malignant pleural mesothelioma.

PMID- 23977537
TI  - Important recent insights into the genetics and biology of malignant pleural
      mesothelioma.

PMID- 23977538
TI  - Mesothelin-targeted immunotherapies for malignant pleural mesothelioma.

PMID- 23977539
TI  - Radical pleurectomy and photodynamic therapy for malignant pleural mesothelioma.

PMID- 23977540
TI  - Radical surgery for malignant pleural mesothelioma: have we identified the
      appropriate selection tools?

PMID- 23977541
TI  - Pleurectomy/decortication, chemotherapy, and intensity modulated radiation
      therapy for malignant pleural mesothelioma: rationale for multimodality therapy
      incorporating lung-sparing surgery.

PMID- 23977542
TI  - Malignant pleural mesothelioma: an epidemiological perspective.
AB  - This paper reviews the aetiology, distribution and projected future incidence of
      malignant mesothelioma. Asbestos exposure is the most thoroughly established risk
      factor. Debate continues regarding the relative importance of the different
      asbestos fibre types and the contribution of Simian virus 40 (SV40). Disease
      incidence varies markedly within and between countries. The highest annual rates
      of disease, approximately 30 case per million, are reported in Australia and
      Great Britain. The risk of disease increases with age and is higher in men. Time
      from asbestos exposure to disease diagnosis is on average greater than 40 years.
      Non-occupational asbestos exposures contribute an increasing proportion of
      disease. With the exception of the United States, incidence continues to
      increase. In developed countries peak incidence is expected to occur before 2030.

PMID- 23977543
TI  - Standardizing surgical treatment in malignant pleural mesothelioma.

PMID- 23977544
TI  - Multimodality therapy for malignant pleural mesothelioma.

PMID- 23977545
TI  - Chemotherapy for malignant pleural mesothelioma: a review of current management
      and a look to the future.

PMID- 23977546
TI  - Inflammation in malignant mesothelioma - friend or foe?

PMID- 23977547
TI  - Extrapleural pneumonectomy and extended pleurectomy/decortication for malignant
      pleural mesothelioma: the Memorial Sloan-Kettering Cancer Center approach.

PMID- 23977548
TI  - Video-atlas of extrapleural pneumonectomy.
AB  - This is a step-by-step video demonstration of a left extrapleural pneumonectomy
      for malignant pleural mesothelioma, including thoracotomy incision, extrapleural
      mobilization of tumor, resection of diaphragm, mediastinal nodal dissection and
      division of hilar vessels followed by reconstruction of diaphragm and closure of
      the thoracotomy. 

PMID- 23977549
TI  - Video-assisted thoracoscopic extrapleural pneumonectomy for malignant pleural
      mesothelioma.

PMID- 23977550
TI  - Video-atlas of radical pleurectomy for malignant pleural mesothelioma.

PMID- 23977551
TI  - Technical pitfalls and solutions in extrapleural pneumonectomy.

PMID- 23977552
TI  - MPM: Malignant Pleural Mesothelioma.

PMID- 23977553
TI  - Systematic review of aortic valve preservation and repair.
AB  - BACKGROUND: Aortic valve repair has emerged as a feasible alternative to
      replacement in the surgical treatment of selected patients with aortic valve (AV)
      pathology. In order to provide a synopsis of the current literature, we preformed
      a systematic review with a focus on valve-related events following AV repair.
      METHODS: Structured keyword searches of Embase and PubMed were performed in
      January 2012. A study was eligible for inclusion if it reported early mortality,
      late mortality, or valve-related morbidity in the adult population. RESULTS:
      Initial search results identified 3,507 unique studies. After applying inclusion
      and exclusion criteria, 111 studies remained for full-text review. Of these, 17
      studies involving 2,891 patients were included for quantitative assessment. No
      randomized trials were identified. Tricuspid and bicuspid AV pathologies were
      present in 65% (range, 21-100%) and 13.5% (range, 5-100%) of the population,
      respectively. Cusp repair techniques were applied in a median of 46% (range, 5
      100%) of patients. The median requirement for early reoperation for post
      operative bleeding and early reintervention for primary AV repair failure was 3%
      (range, 0-10%) and 2% (range, 0-16%), respectively. Pooled early mortality was
      2.6% (95% CI: 1.4-4.4%, I(2) =0%). Late mortality and valve-related events were
      linearized [(number of events/number of patient-years) *100] (%/pt-yr) for each
      study. Late operated valve endocarditis was reported at median event rate of
      0.23%/pt-yr (range, 0-0.78%/pt-yr), while a composite outcome of neurological
      events and thromboembolism occurred at a median rate of 0.52%/pt-yr (0-0.95%/pt
      yr). Late AV re-intervention requiring AV replacement or re-repair occurred at a
      rate of 2.4%/pt-yr (range, 0-4.2%/pt-yr). The median 5-year freedom from AV re
      intervention and late recurrent aortic insufficiency >2+ estimated from survival
      curves was 92% (range, 87-98%) and 88% (range, 87-100%), respectively. Pooled
      late mortality produced summary estimate of 1.3%/pt-yr (95% CI: 0.9-2.1%, I(2)
      =0%). CONCLUSIONS: The present systematic review confirmed the low operative risk
      of patients who underwent aortic valve preservation and repair. There is a need
      for long-term follow-up studies with meticulous reporting of outcomes following
      AV repair, as well as comparative studies with aortic valve replacement.

PMID- 23977555
TI  - Aortic valve sparing operations: outcomes at 20 years.

PMID- 23977554
TI  - Systematic review and meta-analysis of transcatheter aortic valve implantation
      versus surgical aortic valve replacement for severe aortic stenosis.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has emerged as an
      acceptable treatment modality for patients with severe aortic stenosis who are
      deemed inoperable by conventional surgical aortic valve replacement (AVR).
      However, the role of TAVI in patients who are potential surgical candidates
      remains controversial. METHODS: A systematic review was conducted using five
      electronic databases, identifying all relevant studies with comparative data on
      TAVI versus AVR. The primary endpoint was all-cause mortality. A number of
      periprocedural outcomes were also assessed according to the Valve Academic
      Research Consortium endpoint definitions. RESULTS: Fourteen studies were
      quantitatively assessed and included for meta-analysis, including two randomized
      controlled trials and eleven observational studies. Results indicated no
      significant differences between TAVI and AVR in terms of all-cause and
      cardiovascular related mortality, stroke, myocardial infarction or acute renal
      failure. A subgroup analysis of randomized controlled trials identified a higher
      combined incidence of stroke or transient ischemic attacks in the TAVI group
      compared to the AVR group. TAVI was also found to be associated with a
      significantly higher incidence of vascular complications, permanent pacemaker
      requirement and moderate or severe aortic regurgitation. However, patients who
      underwent AVR were more likely to experience major bleeding. Both treatment
      modalities appeared to effectively reduce the transvalvular mean pressure
      gradient. CONCLUSIONS: The available data on TAVI versus AVR for patients at a
      higher surgical risk showed that major adverse outcomes such as mortality and
      stroke appeared to be similar between the two treatment modalities. Evidence on
      the outcomes of TAVI compared with AVR in the current literature is limited by
      inconsistent patient selection criteria, heterogeneous definitions of clinical
      endpoints and relatively short follow-up periods. The indications for TAVI should
      therefore be limited to inoperable surgical candidates until long-term data
      become available.

PMID- 23977556
TI  - Influence of higher valve gradient on long-term outcome after aortic valve
      repair.
AB  - BACKGROUND: To evaluate the effect of higher post-operative valve gradient on
      freedom from valve re-intervention and death in patients undergoing aortic valve
      repair (AVr). METHODS: Patients who underwent AVr between March 1996 and June
      2010 were divided into 2 groups: I: peak gradient (PG) <20 mmHg (n=358) and II:
      PG >=20 mmHg (n=113). Age (53.6+/-16.0 vs. 50.6+/-16.4 years; P=0.08), impaired
      LV (n=44, 12.2% vs. n=12, 10.6%: P=0.73) as well as the body surface area (1.97
      vs. 1.95 m(2); P=0.4) were similar. Pre-operative AI >2+ was greater in Group II
      compared to Group I (n=78, 69.0% vs. n=192, 53.6%; P=0.004). Patients in Group II
      had higher proportion of bicuspid valves (BV) (n=58, 51.3% vs. n=106, 29.6%;
      P=0.0001) and restrictive valves (n=34, 30.0% vs. n=52, 14.5%; P=0.0001) while
      Marfan patients were seen only in Group I (n=19; P=0.010). Mean follow-up for
      Group I and Group II was 123.1+/-89.7 and 147.1+/-108.0 months, respectively.
      RESULTS: In-hospital mortality was n=2 (0.5%) for Group I and none for Group II
      (P=1.0). Valve-sparing was higher in Group I (P=0.0001) but sub-commissural
      annuloplasty was similar (P=0.15). Shaving and/or decalcification was performed
      more in Group II (n=68, 60.1% vs. n=117, 32.6%; P=0.0001). Logistic regression
      analysis identified calcified, restrictive and bicuspid valves as independent
      predictors of PG >=20 mmHg (P=0.04 for each). Predictors of re-operation were
      increased end-diastolic diameter (P=0.03) and younger age (P=0.007), but not PG
      >=20 mmHg (P=0.98) (based on logistic regression). Overall 10-year cardiac
      survival and freedom from AV re-intervention was 82.3+/-4.6% vs. 89.5+/-4.2%
      (P=0.53) and 89.1+/-3.0% vs. 76.8+/-8.4% (P=0.02), in Group I and II,
      respectively (based on Kaplan-Meier analysis). Sub-group analysis showed that
      Group II patients requiring re-intervention (n=10) were younger (41.8+/-13.1 vs.
      51.0+/-16.0 years; P=0.08) with similar proportion of bicuspid valves (n=6; 60%;
      P=0.74). The main reason for AV re-operation was aortic insufficiency (n=7) and
      AI + stenosis (n=3). CONCLUSIONS: Higher gradient after AVr is associated with a
      reduced freedom from AV re-intervention, especially in younger patients.

PMID- 23977557
TI  - Hemodynamics of the aortic valve and root: implications for surgery.

PMID- 23977558
TI  - Aortic valve sparing operations in aortic root aneurysms: remodeling or
      reimplantation?

PMID- 23977559
TI  - Anatomy of the aortic root: implications for valve-sparing surgery.

PMID- 23977560
TI  - Anatomy and pathophysiology of the ventriculo-aortic junction: implication in
      aortic valve repair surgery.

PMID- 23977561
TI  - The role of echocardiography in aortic valve repair.

PMID- 23977562
TI  - Genes in thoracic aortic aneurysms/dissections - do they matter?

PMID- 23977563
TI  - The genetic and molecular basis of bicuspid aortic valve associated thoracic
      aortopathy: a link to phenotype heterogeneity.

PMID- 23977565
TI  - Aortic valve repair in children.

PMID- 23977564
TI  - The surgical implications of bicuspid aortopathy.

PMID- 23977566
TI  - How to perform valve sparing reimplantation in a tricuspid aortic valve.
AB  - Aortic valve sparing procedures are increasingly being used to treat aortic root
      pathologies. Reimplantation of the aortic valve, first described by Dr Tirone
      David, is a technically demanding procedure whose long-term results are
      critically dependent on perfect intraoperative restoration of valve anatomy and
      function. There exists significant variation in how this procedure is performed
      by different surgeons, which is likely contributory to the heterogeneity in
      reported results. We describe a systematic approach to aortic valve
      reimplantation procedure focusing on key technical aspects. 

PMID- 23977567
TI  - Root remodeling for aortic root dilatation.

PMID- 23977569
TI  - Video-atlas of aortic valve repair.

PMID- 23977568
TI  - Valve sparing root replacement: the remodeling technique with external ring
      annuloplasty.

PMID- 23977570
TI  - Valve-sparing aortic root reimplantation and cusp repair in bicuspid aortic
      valve: with aortic insufficiency and root aneurysm.

PMID- 23977571
TI  - Complications after aortic valve repair and valve-sparing procedures.

PMID- 23977572
TI  - Graft sizing for aortic valve sparing surgery.

PMID- 23977573
TI  - Re: Systematic review and meta-analysis of transcatheter aortic valve
      implantation versus surgical aortic valve replacement for severe aortic stenosis.

PMID- 23977574
TI  - Aortic valve repair.

PMID- 23977575
TI  - A meta-analysis of deep hypothermic circulatory arrest versus moderate
      hypothermic circulatory arrest with selective antegrade cerebral perfusion.
AB  - INTRODUCTION: A recent concern of deep hypothermic circulatory arrest (DHCA) in
      aortic arch surgery has been its potential association with increased risk of
      coagulopathy, elevated inflammatory response and end-organ dysfunction. Recently,
      moderate hypothermic circulatory arrest (MHCA) with selective antegrade
      circulatory arrest (SACP) seeks to negate potential hypothermia-related
      morbidities, while maintaining adequate neuroprotection. The present meta
      analysis aims to compare postoperative outcomes in arch surgery using DHCA or
      MHCA+SACP as neuroprotective strategies. METHODS: Electronic searches were
      performed using six databases from their inception to January 2013. Two reviewers
      independently identified all relevant studies comparing DHCA with MHCA+SACP, as
      defined by a recent hypothermia temperature consensus. Data were extracted and
      meta-analyzed according to pre-defined clinical endpoints. RESULTS: Nine
      comparative studies were identified for inclusion in the present meta-analysis.
      Stroke rates were significantly lower in patients undergoing MHCA+SACP (P=0.0007,
      I(2)=0%), while comparable results were observed with temporary neurological
      deficit, mortality, renal failure or bleeding. Infrequent and inconsistent
      reporting of systemic outcomes precluded analysis of other systemic outcomes.
      CONCLUSIONS: The present meta-analysis indicated the superiority of MHCA+SACP in
      terms of stroke risk.

PMID- 23977576
TI  - Perfusion and cannulation strategies for neurological protection in aortic arch
      surgery.

PMID- 23977577
TI  - Consensus on hypothermia in aortic arch surgery.
AB  - Considered a standard part of aortic arch surgery, hypothermia can sufficiently
      reduce cerebral metabolic demand to permit reasonable periods of circulatory
      arrest. Yet despite its ubiquitous application and critical importance,
      temperature classification in hypothermic circulatory arrest is still without
      clear definition. The following Consensus from experts in high-volume aortic
      institutions defines 'profound', 'deep', 'moderate', and 'mild' hypothermia and
      recommends standardized monitoring sites, so as to facilitate more consistent
      reporting and robust analysis. 

PMID- 23977578
TI  - Total arch replacement using selective antegrade cerebral perfusion as the
      neuroprotection strategy.
AB  - BACKGROUND: Optimal neuro-protection strategy in aortic arch surgery is a
      controversial issue. The present study reported surgical outcomes of total arch
      replacement using selective antegrade cerebral perfusion (SACP). METHODS: From
      January 2002 to December 2012, 438 consecutive patients (mean age 69.1+/-13.4
      years) underwent total arch replacement using SACP through a median sternotomy.
      Acute aortic dissection was present in 86 patients (18.3; 80 type A, 6 type B)
      and shaggy aorta in 36 (8.2%). Emergent/urgent surgery was required in 144
      (32.9%). Our current approach included: (I) meticulous selection of arterial
      cannulation site and type of arterial cannula; (II) selective antegrade cerebral
      perfusion; (III) maintenance of minimal tympanic temperature between 20 and 23 
      degrees C; (IV) early re-warming after distal anastomosis; and (V) maintaining
      fluid balance below 1,000 mL during cardiopulmonary bypass. A woven Dacron four
      branch graft was used in all patients. RESULTS: Overall hospital mortality was
      4.6% (20/438). Hospital mortality was 9.7% (14/144) in urgent/emergent surgery
      and 2.0% (6/294) in elective cases. Permanent neurological deficit occurred in
      5.3% (23/438) of patients. Prolonged ventilation was necessary in 58 patients
      (13.2%). Multivariate analysis demonstrated that risk factors for hospital
      mortality were octogenarian (OR 4.45, P=0.03), brain malperfusion (OR 23.52,
      P=0.002) and cardiopulmonary bypass time (OR 1.07, P=0.04). The follow-up was
      completed in 97.9% with mean follow up of 2.3+/-2.3 years. Survival at 5 and 10
      years after surgery was 79.6+/-3.3% and 71.2+/-5.0% respectively. In the acute
      type A dissection group, 10-year survival was 96.8+/-2.9%, while in the elective
      non-dissection group 5- and 10-year survival were 81.4+/-7.2% and 77.0+/-5.9%
      respectively. CONCLUSIONS: Our current approach for total aortic arch replacement
      utilizing SACP was associated with low hospital mortality and morbidities leading
      to favorable long-term outcome.

PMID- 23977579
TI  - Influence of operative strategy for the aortic arch in DeBakey type I aortic
      dissection - analysis of the German Registry for Acute Aortic Dissection type A
      (GERAADA).

PMID- 23977580
TI  - Open aortic arch reconstruction.

PMID- 23977581
TI  - Degree of hypothermia in aortic arch surgery - optimal temperature for cerebral
      and spinal protection: deep hypothermia remains the gold standard in the absence
      of randomized data.

PMID- 23977582
TI  - "Branch-first" continuous perfusion aortic arch replacement and its role in intra
      operative cerebral protection.

PMID- 23977583
TI  - Should the dissected aortic arch be replaced in acute type A dissection? The Mayo
      Clinic perspective.

PMID- 23977584
TI  - Strategies in the surgical treatment of type A aortic arch dissection.

PMID- 23977585
TI  - Type A aortic dissection: the extent of surgical intervention.

PMID- 23977586
TI  - We should replace the aortic arch and more in DeBakey type I dissection - A
      perspective from the Cleveland Clinic.

PMID- 23977587
TI  - Surgical techniques of total arch replacement using selective antegrade cerebral
      perfusion.

PMID- 23977588
TI  - Continuous perfusion "Branch-first" aortic arch replacement: a technical
      perspective.

PMID- 23977589
TI  - Total arch replacement with selective antegrade cerebral perfusion and mild
      hypothermic circulatory arrest.

PMID- 23977590
TI  - Cerebral protection in hemi-aortic arch surgery.

PMID- 23977591
TI  - Aortic arch surgery.

PMID- 23977592
TI  - A systematic review and meta-analysis of hybrid aortic arch replacement.
AB  - BACKGROUND: Evolution in the endovascular era has influenced the management of
      aortic arch pathologies. Several studies have described the use of a combined
      endovascular and open surgical approach to the treatment of arch diseases. Hybrid
      repair of arch pathologies has been considered as a less invasive method, and is
      therefore an appealing option for high-risk patients who are unsuitable for open
      repairs. The aim of the present meta-analysis was to assess the efficacy of
      hybrid techniques in patients with aortic arch pathologies. METHODS: Extensive
      electronic literature search was undertaken to identify all articles published up
      to December 2012 that described hybrid aortic arch repair with intrathoracic
      supra-aortic branch revascularisation and subsequent stent graft deployment.
      Eligible studies were divided into two groups: group I included studies on the
      aortic arch debranching procedure and group II included studies that reported an
      elephant trunk technique (either "frozen" or stented). Separate meta-analyses
      were conducted in order to assess technical success, stroke, spinal cord ischemia
      (SCI), renal failure requiring dialysis, and cardiac and pulmonary complications
      rate, as well as 30-day/in-hospital mortality. RESULTS: Forty-six studies were
      eligible for the present meta-analysis: 26 studies with a total of 956 patients
      reported aortic arch debranching procedures, and 20 studies with 1,316 patients
      performed either 'frozen' or stented elephant trunk technique. The pooled
      estimate for 30-day/in-hospital mortality was 11.9% for the arch debranching
      group and 9.5% for the elephant trunk group. Cerebrovascular events of any
      severity were found to have occurred postoperatively at a pooled rate of 7.6% and
      6.2%, while irreversible spinal cord injury symptoms were present in a pooled
      estimate of 3.6% and 5.0% in the arch debranching and elephant trunk group,
      respectively. Renal failure requiring dialysis occurred at 5.7% and 3.8% in both
      groups, while cardiac complications rate was 6.0% in the arch debranching cohort
      and pulmonary complication was 19.7% in the elephant trunk cohort. CONCLUSIONS:
      Hybrid arch techniques provide a safe alternative to open repair with acceptable
      short- and mid-term results. However, stroke and mortality rates remain
      noteworthy. Future prospective trials that compare open conventional techniques
      with the hybrid method or the entirely endovascular methods are needed.

PMID- 23977593
TI  - A meta-analysis of deep hypothermic circulatory arrest alone versus with
      adjunctive selective antegrade cerebral perfusion.
AB  - INTRODUCTION: Recognizing the importance of neuroprotection in aortic arch
      surgery, deep hypothermic circulatory arrest (DHCA) now underpins operative
      practice as it minimizes cerebral metabolic activity. When prolonged periods of
      circulatory arrest are required, selective antegrade cerebral perfusion (SACP) is
      supplemented as an adjunct. However, concerns exist over the risks of SACP in
      introducing embolism and hypo- and hyper-perfusing the brain. The present meta
      analysis aims to compare postoperative outcomes in arch surgery using DHCA alone
      or DHCA + SACP as neuroprotection strategies. METHODS: Electronic searches were
      performed using six databases from their inception to January 2013. Two reviewers
      independently identified all relevant studies comparing DHCA alone with DHCA +
      SACP. Data were extracted and meta-analyzed according to pre-defined clinical
      endpoints. RESULTS: Nine comparative studies were identified in the present meta
      analysis, with 648 patients employing DHCA alone and 370 utilizing DHCA + SACP.
      No significant differences in temporary or permanent neurological outcomes were
      identified. DHCA + SACP was associated with significantly better survival
      outcomes (P=0.008, I(2)=0%), despite longer cardiopulmonary bypass time.
      Infrequent and inconsistent reporting of other clinical results precluded
      analysis of systemic outcomes. CONCLUSIONS: The present meta-analysis indicate
      the superiority of DHCA + SACP in terms of mortality outcomes.

PMID- 23977594
TI  - The genetics and genomics of thoracic aortic disease.
AB  - Genetic studies over the past several decades have helped to better elucidate the
      genomics and inheritance of thoracic aortic diseases. Seminal work from various
      researchers have identified several genetic factors and mutations that predispose
      to aortic aneurysms, which will aid in better screening and early intervention,
      resulting in better clinical outcomes. Syndromic aneurysms have been associated
      with Marfan syndrome, Loeys-Dietz syndrome, aneurysm osteoarthritis syndrome,
      arterial tortuosity syndrome, Ehlers-Danlos Syndrome, and TGFbeta mutation.
      Mutations in MYH11, TGFbetaR1, TGFbetaR2, MYLK, and ACTA2 genes have been linked
      to familial non-syndromic cases, although linkage analysis is limited by
      incomplete penetrance and/or locus heterogeneity. This overview presents a
      summary of key genetic and genomic factors that are associated with thoracic
      aortic diseases. 

PMID- 23977595
TI  - Type I and Type II hybrid aortic arch replacement: postoperative and mid-term
      outcome analysis.
AB  - BACKGROUND: Hybrid aortic arch replacement has emerged as a safe treatment
      modality for arch aneurysms, especially in patients of old age and with greater
      comorbid burden. We assessed our institutional outcomes in patients undergoing
      Types I and II hybrid aortic arch replacement. METHODS: From 2005 to 2012, 685
      patients underwent thoracic endovascular repair (TEVAR), of whom 104 had hybrid
      arch repair (open + endovascular approach). 47 of these patients had treatment
      for aortic arch aneurysm +/- proximal ascending aortic aneurysm. The hybrid
      repair entailed aortic arch vessel debranching and concomitant/delayed antegrade
      +/- retrograde TEVAR stent grafting of the arch. Type III patients were excluded
      from the analysis. Data was prospectively maintained. RESULTS: 28 patients had
      Type I repair, 8 had Type II repair, and 11 had Type III repair. Mean age was
      71+/-8 years. Primary aortic pathology was aneurysm (81%), followed by chronic
      arch dissection (11%). 14% of patients required reoperative cardiac surgery.
      Stent graft deployment rate was 100% after arch vessel debranching. Postoperative
      endoleak rate was zero. Average cardiopulmonary bypass time was 215+/-64 minutes,
      with crossclamp time of 70+/-55 minutes, and circulatory arrest time of 50+/-17
      minutes. Paraplegia rate was 5.5% (n=2), with stroke rate of 8% (n=3) and renal
      failure rate of 3% (n=1) requiring hemodialysis. In-hospital mortality was 8%
      (n=3). Mean length of stay was 17.2+/-14 days. Median follow-up was 30+/-21
      months. Freedom from all-cause mortality was 71%, 60%, and 48% at 1, 3, and 5
      years respectively. Aortic reoperation rate was 2.7% (n=1). No patient had Type I
      or III endoleak at follow-up. Freedom from mortality was improved in cases
      performed more recently (July 2008 to 2012) than during our early experience
      (2005 to June 2008) (81% versus 44% at 3 years, P=0.05). CONCLUSIONS: Hybrid
      aortic arch replacement can be performed with good postoperative and midterm
      results in a cohort of old patients with significant comorbidity. With greater
      experience, early and midterm outcomes continue to improve. The hybrid arch
      technique may represent a technical advancement in the field of aortic arch
      surgery.

PMID- 23977596
TI  - Aortic arch surgery using moderate hypothermia and unilateral selective antegrade
      cerebral perfusion.
AB  - BACKGROUND: Cerebral protection and circulatory management remains a
      controversial issue in aortic arch surgery. The present study reported surgical
      outcomes of arch repair using moderate hypothermic circulatory arrest (MHCA) and
      unilateral selective antegrade perfusion (uSACP). METHODS: From January 2004 and
      December 2012, 500 patients underwent hemiarch repair (HARCH) and 124 underwent
      total arch replacement (TARCH) utilizing moderate hypothermic circulatory arrest
      with unilateral selective antegrade cerebral perfusion of the right axillary
      artery. Emergent surgery was required in 142 (28.4%) of HARCH patients and 18
      (14.5%) of TARCH patients. Mean arrest temperature ranged from 25.6-27.2  degrees
      C for elective and emergent operations in both groups. Mean circulatory arrest
      was 26.8 minutes for hemiarch repairs and 54.2 minutes for total arch
      replacement. RESULTS: Overall mortality was 6.6% for hemiarch repairs and 9.7%
      for total arch replacements. Hospital mortality was 4.5% (16/358) and 10.4%
      (11/106) in elective cases, and 12% (17/142) and 5.6% (1/18) in elective cases,
      for hemiarch and total arch replacements respectively. Permanent neurological
      deficit (PND) occurred in 3 total arch replacement cases (2.4%). Multivariate
      analysis demonstrated that temperature was not found to be an independent risk
      factor during hemiarch or total arch replacements for mortality, permanent or
      neurological deficits, or renal failure. CONCLUSIONS: Our approach for hemiarch
      and total arch repair utilizing MHCA and uSACP via the right axillary artery was
      associated excellent neurological and survival outcomes. Moderate hypothermia did
      not adversely impact cerebral or visceral organ protection.

PMID- 23977597
TI  - International E-vita open registry.
AB  - The E-vita open hybrid stent-graft enables successful one-stage repairs of
      complex pathologies of the ascending aorta, aortic arch, and descending aorta. To
      evaluate the efficacy and durability of this treatment concept, the International
      E-vita open registry (IEOR) was initiated in 2008. 416 patients from 10 European
      centers were recruited, separated into 138 (33.2%) acute dissection cases, 142
      (34.1%) chronic dissection cases, and 136 (32.7%) patients with multisegmental
      thoracic aneurysmal disease. In-hospital mortality was 16%, 14%, and 13% for each
      of the three groups, respectively, and stroke and spinal cord injury rates ranged
      between 5-7% and 3-9%. Survival after 5 years was 79%, 86%, and 78% for acute
      dissection, chronic dissection, and multisegmental aneurysmal patients, with
      freedom from open aortic surgery after 5 years at 96%, 94% and 82%. Findings from
      IEOR demonstrate the importance of the registry as an important tool for
      developing guidelines and frameworks in the management of this complex pathology.

PMID- 23977598
TI  - Hybrid aortic arch repair.
AB  - Innovations in thoracic endovascular aortic repair techniques have enabled its
      incorporation in open procedures, resulting in a hybrid approach to aortic arch
      repair. The present study reported our experience with the hybrid technique in
      managing arch pathologies. Fifty-one patients underwent a hybrid repair of arch
      pathologies. 10 patients had urgent or emergency surgery, and 8 had previous
      abdominal aortic aneurysm repair; all were classified as high risk (ASA grade III
      or IV). Overall 30-day mortality was 9.8% (5/51). Hospital mortality was 30%
      (3/10) in urgent/emergent surgery and 4.90% (2/41) in elective cases. Ischemic
      stroke occurred in 11.8% (6/51) of patients, while 5.9% (3/51) experienced
      paraplegia. Endoleaks occurred in 8 patients, 6 of which were Type 1. Long-term
      patency rate was 96%. The hybrid technique is a safe, effective and less invasive
      alternative to open repair of arch pathologies, with comparable outcomes in high
      risk patient groups. Patency rates and durability demonstrate the long-term
      potential of this technique. 

PMID- 23977599
TI  - Deep hypothermic circulatory arrest.
AB  - Effective cerebral protection remains the principle concern during aortic arch
      surgery. Hypothermic circulatory arrest (HCA) is entrenched as the primary
      neuroprotection mechanism since the 70s, as it slows injury-inducing pathways by
      limiting cerebral metabolism. However, increases in HCA duration has been
      associated with poorer neurological outcomes, necessitating the adjunctive use of
      antegrade (ACP) and retrograde cerebral perfusion (RCP). ACP has superseded RCP
      as the preferred perfusion strategy as it most closely mimic physiological
      perfusion, although there exists uncertainty regarding several technical details,
      such as unilateral versus bilateral perfusion, flow rate and temperature,
      perfusion site, undue trauma to head vessels, and risks of embolization.
      Nevertheless, we believe that the convenience, simplicity and effectiveness of
      straight DHCA justifies its use in the majority of elective and emergency cases.
      The following perspective offers a historical and clinical comparison of the DHCA
      with other techniques of cerebral protection. 

PMID- 23977600
TI  - A reappraisal of retrograde cerebral perfusion.
AB  - Brain protection during aortic arch surgery by perfusing cold oxygenated blood
      into the superior vena cava was first reported by Lemole et al. In 1990 Ueda and
      associates first described the routine use of continuous retrograde cerebral
      perfusion (RCP) in thoracic aortic surgery for the purpose of cerebral protection
      during the interval of obligatory interruption of anterograde cerebral flow. The
      beneficial effects of RCP may be its ability to sustain brain hypothermia during
      hypothermic circulatory arrest (HCA) and removal of embolic material from the
      arterial circulation of the brain. RCP can offer effective brain protection
      during HCA for about 40 to 60 minutes. Animal experiments revealed that RCP
      provided inadequate cerebral perfusion and that neurological recovery was
      improved with selective antegrade cerebral perfusion (ACP), however, both RCP and
      ACP provide comparable clinical outcomes regarding both the mortality and stroke
      rates by risk-adjusted and case-matched comparative study. RCP still remains a
      valuable adjunct for brain protection during aortic arch repair in particular
      pathologies and patients. 

PMID- 23977601
TI  - Selective cerebral perfusion for cerebral protection: what we do know.
AB  - Selective antegrade cerebral perfusion (SACP) for aortic arch surgery has evolved
      considerably since it was first reported. Various pressure rates have been
      investigated through animal models, as has the effect of warmer perfusate
      temperatures and hematocrit. Clinical research into pH management, the role of
      unilateral and bilateral perfusion, and core temperatures have further refined
      the procedure. We recommend the following protocol for SACP: perfusion pressure
      between 40-60 mmHg, flow rates between 6-10 mL/kg/min, and perfusate temperature
      of 20-28  degrees C; core cooling to 18-30  degrees C contingent on duration of
      arrest; alpha-stat pH management; hematocrit between 25-30%; near infrared
      spectroscopy to monitor cerebral perfusion; and bilateral perfusion when
      prolonged durations of SACP is anticipated. 

PMID- 23977602
TI  - Best strategy for cerebral protection in arch surgery - antegrade selective
      cerebral perfusion and adequate hypothermia.
AB  - Aortic arch surgery remains a complex surgical operation that necessitates
      specific neuroprotection strategies. Various approaches, such as hypothermic
      circulatory arrest (HCA), retrograde cerebral perfusion, and antegrade selective
      cerebral perfusion (aSCP), have each enjoyed periods of popularity. However,
      while the overall surgical approach tend to favour HCA with aSCP, technical
      factors, such as perfusion site, perfusate temperature and flow rate and pH
      management, have not been conclusively elucidated. The optimal extent of
      hypothermia during circulatory arrest is also unclear, particularly with recent
      partiality for warmer temperatures. The following perspective details the
      preferred surgical practice for cerebral protection in aortic arch surgery, based
      on existing evidence. 

PMID- 23977603
TI  - The chimney-graft technique for preserving supra-aortic branches: a review.
AB  - Evolution in the endovascular era has influenced the management of aortic arch
      pathologies. "Chimney" or "snorkel" graft technique has been used as an
      alternative in high risk patients unfit for open repair. We reviewed the
      published literature on the chimney graft technique for preservation of the supra
      aortic branches in order to provide an extensive insight of its feasibility and
      efficacy and investigate its outcomes. 18 reports were identified, with a total
      of 124 patients and 136 chimney. Primary technical success was achieved in
      123/124 patients (99.2%). The perioperative mortality rate was 4.8% and the
      stroke rate was 4%, while events of spinal cord ischemia were rare. The overall
      endoleak rate was 18.5%; 13 patients (10.5%) developed a type I endoleak and 10
      (8%) patients a type II endoleak. During a median follow-up period of 11.4 months
      (range, 0.87-20.1 months) all implanted chimney grafts remained patent. From
      this, we conclude that endovascular aortic arch repair with chimney grafts is
      associated with a lower mortality rate compared to totally open or hybrid
      reconstruction. However, the stroke rate remains noteworthy, and requires
      longterm data to elucidate. 

PMID- 23977604
TI  - Total aortic arch replacement: current approach using the trifurcated graft
      technique.
AB  - Since the pioneering work of DeBakey, Cooley, and colleagues more than 50 years
      ago, surgical treatment of aneurysms involving the transverse aortic arch has
      been associated with substantial morbidity and mortality. Over the past 15 years,
      techniques for replacing the diseased aortic arch have evolved substantially.
      Previously, our approach to these operations involved femoral cannulation,
      profound-to-deep hypothermic circulatory arrest and retrograde cerebral
      perfusion, and the island technique for reattaching the brachiocephalic vessels.
      In contrast, we currently use innominate artery cannulation, deep-to-moderate
      hypothermic circulatory arrest with antegrade cerebral perfusion, bilateral
      cerebral monitoring with near-infrared spectroscopy, and the trifurcated graft (Y
      graft) technique for reattaching the arch branches. Cannulating the innominate
      artery to provide an inflow site for cardiopulmonary bypass has facilitated the
      use of antegrade cerebral perfusion as a cerebral protection strategy; the left
      common carotid artery is additionally perfused to provide bilateral cerebral
      perfusion. Despite having a systemic circulatory arrest time that often exceeds
      60 minutes, these improved perfusion strategies make it possible to consistently
      avoid cerebral circulatory arrest all together. A moderate temperature target of
      between 18 and 23  degrees C is now used; this appears to reduce the risk of
      hypothermic coagulopathy and improve hemostasis. Y-graft techniques, such as the
      trifurcated graft approach, have the advantages of eliminating residual aortic
      arch tissue and being easily tailored to the needs of the individual patient.
      This report describes total aortic arch replacement in patients with aneurysms
      that are confined to the ascending aorta and transverse aortic arch. 

PMID- 23977605
TI  - Total arch replacement with separated graft technique and selective antegrade
      cerebral perfusion.
AB  - It is essential to select the optimum method of cerebral protection and operative
      technique for arch repair to improve the surgical outcome of arch aneurysm or
      dissection. Selective antegrade cerebral perfusion (SACP) is our current method
      of choice if required cerebral protection time exceeds 30 minutes. Moderate
      hypothermic two-arch vessel perfusion (innominate artery or right axillary artery
      and left common carotid artery) is safe and effective for brain protection in a
      majority of patients. The separated graft technique using 4-branched graft is now
      our preferred surgical procedure used for arch aneurysm or dissection because
      this technique presents several advantages over the en-bloc or island technique.
      SACP allows us to perform meticulous arch repair and facilitates the time
      consuming total arch replacement for complex aortic arch pathology and results in
      an acceptable mortality (less than 4%) and morbidity (stroke 3%). 

PMID- 23977606
TI  - Aortic arch/elephant trunk procedure with Sienna(TM) graft and endovascular
      stenting of thoraco-abdominal aorta for treatment of complex chronic dissection.
AB  - Aneurismal dilatation of the remaining thoracic aorta after ascending aortic
      interposition grafting for type 'A' aortic dissection is not uncommon. For such
      complex cases, one treatment option is total arch replacement and elephant trunk
      procedure with the Sienna(TM) collared graft (Vascutek, Inchinnan, UK) technique
      followed by a staged thoracic endovascular aortic repair (TEVAR). The video
      illustrates our technique in a 56-year-old man with an extensive aortic arch and
      descending thoracic aortic dissecting aneurysm. For the 'open' procedure femoral
      arterial and venous cannulation was used along with systemic cooling and
      circulatory arrest at 22  degrees C. Upon circulatory arrest, the aortic arch was
      incised and antegrade cerebral perfusion achieved via selective cannulation to
      the right brachiocephalic and left common carotid artery, keeping flow rates at
      10-15 mL/kg/min and perfusion pressure at 50-60 mmHg. Arch replacement with an
      elephant trunk component was then performed and after completion of the distal
      aortic anastomosis antegrade perfusion via a side-arm in the graft was started
      and the operation completed using a variation of the 'sequential' clamping
      technique to maximize cerebral perfusion. The second endovascular stage was
      performed two weeks after discharge. Two covered stents were landing from the
      elephant trunk to the distal descending thoracic aorta, to secure the distal
      landing a bare stent of was placed to cover the aorta just distal to the origin
      of the celiac axis. The left subclavian artery was embolised with fibre coils.
      Post TEVAR angiogram showed no endoleak Although re-operative total arch
      replacement and elephant trunk procedure and subsequent TEVAR remained a
      challenging procedure, we believe excellent surgical outcome can be achieved with
      carefully planned operative strategy. 

PMID- 23977607
TI  - Total endograft replacement of aortic arch.
AB  - Total endovascular replacement of the aortic arch is a complex procedure that is
      often favoured when the pathology anatomy precludes a standard median sternotomy.
      Here we present the case of endograft repair in a 79 year old male with 6.5 cm
      arch aneurysm and 5.4 cm descending thoracoabdominal aneurysm. Following
      bilateral carotid-subclavian bypasses, a long 7 Fr sheath was advanced into the
      descending aorta through the common iliac artery purse string. A double curved
      long Lunderquist wire was guided to deep within the left ventricle, and the
      endograft carefully advanced over the wire. The graft was radiologically
      orientated, and deployed under asystolic conditions. Retrograde cannulation of
      the branches were accomplished, with carotid sheath placed into the branches
      followed by bridging stents. The graft delivery system was then removed. This
      approach obviates the need for a sternotomy, cumbersome extra-anatomic
      debranching, and hypothermic circulatory arrest. 

PMID- 23977608
TI  - Total arch replacement using antegrade cerebral perfusion for distal aortic arch
      aneurysm.
AB  - Total aortic arch replacement remains a complex surgical procedure, best
      practiced in high-volume aortic centers. The following report details the
      surgical procedure for total arch replacement with selective antegrade cerebral
      perfusion (SACP) for distal arch aneurysm. Following moderate hypothermic
      circulatory arrest and SACP, the distal arch, and then the proximal arch, is
      reconstructed, followed by re-implantation of epi-aortic vessels. 

PMID- 23977609
TI  - Techniques for repair of retrograde aortic dissection following thoracic
      endovascular aortic repair.
AB  - The advances in thoracic endovascular aortic repair (TEVAR) offer patients who
      are otherwise unsuitable for open surgery an alternative in treating their aortic
      arch pathologies. However, the adoption of TEVAR carries inherent complications
      unique to itself, notably the occurrence of Type A retrograde ascending aortic
      dissections, which can range from 1-3%. Several key technical considerations are
      must be heeded to minimize the risks of these complications. It is important to
      completely excise the primary entry tear through a careful and methodical
      approach. The proximal and distal reconstruction must be hemodynamically sound,
      with care taken to stabilize both the root and the distal aorta. Neuroprotection
      strategies, such as antegrade cerebral perfusion, should be utilized if the
      duration of circulatory arrest is anticipated to be greater than 30 minutes. This
      report details the operative techniques for the repair of retrograde aortic
      dissections following TEVAR. 

PMID- 23977610
TI  - Hybrid aortic arch repair.
AB  - The successes of thoracic endovascular aortic repair (TEVAR) have spurned new
      approaches to addressing thoracic aortic pathologies. These hybrid techniques
      offer an alternative in patients with multi-segmental thoracic aortic pathologies
      which would have otherwise required a two-step arch replacement and open
      descending arch repair. The following article offers a clinical insight to the
      available hybrid approaches, such as rerouting of supra-aortic vessels. Unique
      complications to endovascular repairs, and technical risks and issues, are also
      presented along with management options and strategies to minimize such concerns.

PMID- 23977611
TI  - Type II arch hybrid debranching procedure.
AB  - Management of aortic arch aneurysm and dissection continues to evolve as
      endovascular options play an increasing role in treating thoracic aortopathies.
      Although conventional open treatment of aortic arch disease with total arch
      replacement still remains the gold standard, in patients with old age and/or high
      comorbid disease index, there is significant associated morbidity and mortality.
      The hybrid arch procedure, which aims to minimize cardiopulmonary bypass and
      circulatory arrest times, is a particularly appealing surgical option in this
      cohort of patients. The hybrid arch concept essentially entails three main
      principles: (I) open debranching of the great vessels; (II) creation of proper
      proximal (zone 0 landing) and distal landing zones, and; (III) concomitant or
      delayed endovascular stent grafting of the aortic arch. The classification scheme
      for hybrid arch debranching procedures is based on the extent of proximal and
      distal landing zone reconstruction required, and thus the need and extent of
      cardiopulmonary bypass and circulatory arrest management strategies to be
      employed. In this illustrated article, we describe the details of the type II
      hybrid arch debranching procedure, where the ascending aorta and aortic arch
      pathology is typically treated by reconstruction of ascending aorta + arch vessel
      debranching, with concomitant antegrade stent grafting of the aortic arch. 

PMID- 23977612
TI  - Aortic surgery and stroke.

PMID- 23977613
TI  - Total Arterial Revascularization-the evidence, the reality and the dilemma.

PMID- 23977614
TI  - A meta-analysis comparing bilateral internal mammary artery with left internal
      mammary artery for coronary artery bypass grafting.
AB  - BACKGROUND: Increasing evidence continues to demonstrate a survival advantage for
      bilateral internal mammary artery (BIMA) over left internal mammary artery (LIMA)
      for coronary artery bypass grafting (CABG). We performed an updated meta-analysis
      of published studies comparing BIMA versus LIMA in CABG operations and assessed
      differences in long-term survival. METHODS: Electronic searches for studies
      comparing BIMA versus LIMA were performed using three databases from 1972 to
      December 2012. Studies with at least four years of follow-up and at least 100
      patients in each group were included for review. We used a random-effect model
      and pooled hazard ratios from across all included studies. RESULTS: No randomized
      controlled trials and 27 observational studies totaling 79,063 patients (19,277
      BIMA, 59,786 LIMA) were included for final analysis. The BIMA group demonstrated
      significantly better long-term survival than the LIMA group [hazard ratio, 0.78;
      confidence interval, 0.72-0.84; P<0.00001]. CONCLUSIONS: In an updated meta
      analysis, we demonstrate an increase in long-term survival in patients receiving
      BIMA as a primary grafting strategy over those receiving a LIMA. Although no
      randomized controlled trials were included in this meta-analysis, the survival
      benefit seen with a BIMA cannot be overlooked when determining which operation to
      perform in CABG patients. Until the long-term results of the ART trial are
      published, we offer best available evidence in favor of BIMA over LIMA for CABG
      surgery.

PMID- 23977615
TI  - A meta-analysis of randomized controlled trials on mid-term angiographic outcomes
      for radial artery versus saphenous vein in coronary artery bypass graft surgery.
AB  - BACKGROUND: Currently, saphenous vein (SV) and radial artery (RA) are the most
      commonly used conduits in combination with the left internal mammary artery for
      conventional coronary artery bypass graft surgery (CABG). The present meta
      analysis aimed to assess the existing evidence from randomized controlled trials
      (RCTs) to compare the angiographic outcomes of these two conduits at mid-term
      follow-up. METHODS: Four relevant and updated RCTs with follow-up beyond 3 years
      were identified using five electronic databases. Angiographic endpoints included
      complete occlusion, 'string sign', graft failure and complete patency. RESULTS:
      The incidence of complete occlusion was significantly lower after using RA
      compared to SV [6.7% vs. 17.2%; odd ratio (OR), 0.36; 95% confidence interval
      (CI), 0.23-0.58; P<0.0001]. The angiographic 'string sign' was significantly more
      likely to be identified after using RA compared to SV (3.1% vs. 0%; OR, 5.65; 95%
      CI, 1.21-26.39; P=0.03). Graft failure was significantly lower after RA compared
      to SV (9.6% vs. 18.8%; OR, 0.47; 95% CI, 0.30-0.72; P=0.0005). Complete graft
      patency was found to be significantly higher after RA compared to SV (88.6% vs.
      75.8%; OR, 3.19; 95% CI, 1.42-7.16; P=0.005). CONCLUSIONS: Results of the present
      meta-analysis suggest that selected patients with severe, proximal stenosis may
      have superior angiographic outcomes at mid-term follow-up after using RA compared
      to SV for CABG. However, RA is associated with a significantly higher incidence
      of the 'string sign'. Future studies should aim to collect additional data on
      symptomatic outcomes.

PMID- 23977616
TI  - Systematic review of robotic-assisted, totally endoscopic coronary artery bypass
      grafting.
AB  - BACKGROUND: Advancements in surgical robotic technology over the last two decades
      have enabled coronary artery bypass grafting to be performed totally
      endoscopically, and have the potential to significantly change clinical practice
      in the future. METHODS: A systematic review of studies reporting clinical
      outcomes of total endoscopic coronary artery bypass grafting (TECABG) was
      performed. RESULTS: 14 appraised studies included 880 beating heart TECABGs, 360
      arrested heart TECABGs, 633 one-vessel operations and 357 two-vessel operations.
      Patients were generally low-risk. There was a significant learning curve. The
      weighted means for short-term beating heart and arrested heart TECABG results
      respectively were: intraoperative exclusion rate of 5.7% and 1.9%, intraoperative
      conversion rate of 5.6% and 15.0%, all-cause mortality of 1.2% and 0.4%, stroke
      of 0.7% and 0.8%, myocardial infarction of 0.8% and 1.8%, new onset atrial
      fibrillation of 10.7% and 5.1% and post-operative reintervention rate of 2.6% and
      2.3%. The overall rate of short term postoperative graft patency for beating
      heart and arrested heart TECABG was 98.3% and 96.4% respectively. CONCLUSIONS:
      Appropriate patient selection was important in minimizing the risk of
      intraoperative and postoperative complications. Short-term outcomes of both
      beating and arrested heart TECABG were acceptable, but results so far have been
      heterogeneous. There were fewer studies reporting intermediate to long-term
      outcomes, but results were encouraging, and further investigation and development
      of the procedure is warranted.

PMID- 23977617
TI  - The history of arterial revascularization: from Kolesov to Tector and beyond.
AB  - Coronary artery bypass grafting (CABG) is the one of the most effective
      revascularization strategies for patients with obstructive coronary artery
      disease. Total arterial revascularization using one or both internal thoracic and
      radial arteries has been shown to improve early outcomes and reduce long-term
      cardiovascular morbidity. Although CABG has evolved from an experimental
      procedure in the early 1900's to become one of the most commonly performed
      surgical procedures, there is still significant variation in grafting strategies
      amongst surgeons. We review the history and development of CABG with a particular
      emphasis on the early pioneers and the evolution of arterial grafting. 

PMID- 23977618
TI  - Current status of arterial grafts for coronary artery bypass grafting.
AB  - For over a decade there has been accumulating evidence that the use of more than
      a single arterial graft during coronary artery bypass grafting can improve
      clinical outcomes. However the vast majority of patients in most developed
      countries still only receive a single arterial conduit even in the presence of
      multivessel coronary artery disease. This review summarizes the current evidence
      for the use of a second internal mammary artery and/or radial artery graft. While
      in comparison to vein grafts the superior patency of internal mammary artery
      grafts is well established, there now exists strong and consistent evidence of
      the superior patency of radial arteries over the longer term. Likewise, there is
      a rapidly growing body of evidence that the superior patency of both these
      arteries in comparison to vein grafts translates into improved clinical outcomes.

PMID- 23977619
TI  - Stents or surgery in coronary artery disease in 2013.
AB  - In addition to optimal medical therapy, some patients with coronary artery
      disease also require intervention on symptomatic and/or prognostic grounds. The
      debate over the relative efficacies of coronary artery bypass grafting (CABG) and
      stenting has recently been settled by the publication of the five-year outcomes
      of the SYNTAX and FREEDOM (in patients with diabetes) trials accompanied by
      supportive data from several large registries. There is also current evidence
      that stenting is still carried out in patients who would be better served by
      CABG, emphasizing the need for recommendations for intervention to be overseen by
      a multidisciplinary team rather than the individual practitioner. 

PMID- 23977621
TI  - Full myocardial revascularization with bilateral internal mammary artery Y
      grafts.
AB  - BACKGROUND: Bilateral internal mammary artery (BIMA) grafting in coronary artery
      surgery provides better long term outcomes than single internal mammary artery
      and saphenous vein grafting but the optimum configuration of BIMAs has not been
      established. This study analyzed perioperative and late outcomes of patients who
      underwent BIMA grafting with a composite Y configuration. METHODS: Patients
      (n=922) who underwent BIMA Y grafting were identified from a cardiac surgical
      database and then cross matched against hospital and cardiology databases and the
      state death register to identify episodes of repeat coronary angiography, cardiac
      surgical re-intervention and death. Analysis of repeat angiography was performed
      after retrieval of the angiogram reports. RESULTS: In 95% of patients, full
      myocardial revascularization was achieved with BIMAs alone, using a composite Y
      configuration with an average of 4.1 IMA to coronary artery anastomoses per
      patient. The perioperative mortality was 1.5% and the 5-, 10- and 15-year
      survival estimates were 95%, 87% and 77% respectively. Analysis of 166 symptom
      driven post-discharge coronary angiograms showed grafts to the left anterior
      descending artery and increasing severity of coronary artery stenosis at
      preoperative angiography as predictors of anastomotic patency. CONCLUSIONS: Full
      myocardial revascularization can be achieved with reasonable safety in most
      patients with triple vessel disease and good left ventricular function, and
      provides good late survival.

PMID- 23977620
TI  - Biomechanics and biocompatibility of the perfect conduit-can we build one?
AB  - No currently available conduit meets the criteria for an ideal coronary artery
      bypass graft. The perfect conduit would combine the availability and complication
      free harvest of a synthetic vessel with the long-term patency performance of the
      internal mammary artery. However, current polymer conduits suffer from inelastic
      mechanical properties and especially poor surface biocompatibility, resulting in
      early loss of patency as a coronary graft. Approaches to manufacture an improved
      conduit using new polymers or polymer surfaces, acellular matrices, or cellular
      constructs have to date failed to achieve a commercially successful alternative.
      Elastin, by mimicking the native extracellular environment as well as providing
      elasticity, provides the 'missing link' in vascular conduit design and brings new
      hope for realization of the perfect conduit. 

PMID- 23977622
TI  - Radial artery as a second arterial graft in the elderly and both sexes.
AB  - BACKGROUND: Use of multiple arterial grafts for surgical coronary
      revascularization remains limited in scope worldwide, and is disproportionately
      low in two growing segments of coronary artery disease patients-women and the
      elderly. While a prevailing practice, this trend is not supported by objective
      data. This report discusses two recent reports that support the liberal use of
      the radial artery (RA) as a second arterial conduit, in the elderly and
      irrespective of sex, instead of the conventional operation based on a single
      internal thoracic artery (ITA) with additional vein grafts. METHODS: From 1996 to
      2007, 6,384 patients underwent primary, non-salvage emergency coronary artery
      bypass grafting with at least 2 complete grafts (including one ITA graft) were
      included in the present analysis. Those with bilateral ITA, ITA-only grafts, or
      concomitant valve/aortic surgery were excluded. 2,605 patients aged 70 or greater
      were further included in a subsequent analysis. Patients were further matched on
      propensity score models based on ITA/RA versus ITA/saphenous vein (SV) grafts.
      RESULTS: 69% of all included patients were male. Propensity models yielded 1,416
      ITA/RA and ITA/SV matched pairs in men and 567 pairs in women. Operative
      mortality was similar for both graft combinations in men and women, while late
      mortality was significantly lower for ITA/RA subcohorts in both sexes. Matched
      Kaplan-Meier cumulative mortality was significantly better for ITA/RA
      irrespective of sex (men: risk reduction (RR) =0.65, P<0.001; women: RR=0.75,
      P=0.045). In patients aged 70 years or older, operative death was essentially
      identical for ITA/RA vs. ITA/SV (2.31% vs. 2.31%; P=0.880). Patients undergoing
      ITA/RA grafting had significantly better unadjusted 12-year survival. In 480
      elderly matched pairs, cumulative mortality at 1, 5, and 10 years was
      significantly better for the ITA/RA cohort. CONCLUSION: The discussed data showed
      a clinically significant improvement in intermediate (1-5 years) and late (>5
      years) survival with multiple arterial grafts in female and male patients and in
      the elderly. The latter was true for both the septuagenarian and octogenarian
      subgroups. Importantly, the choice of the RA as the second arterial conduit seems
      to be associated with low associated perioperative risks, and avoids the
      potential for sternal healing complications due to bilateral ITA dissection in
      certain patients.

PMID- 23977623
TI  - Mid-term results of the Radial Artery Patency and Clinical Outcomes randomized
      trial.
AB  - BACKGROUND: The radial artery (RA), as an alternative to the saphenous vein or
      the right internal thoracic artery (RITA) for coronary artery bypass grafting,
      has gained considerable interest over the years. A randomized controlled trial
      was undertaken to assess the suitability of the radial artery as a conduit.
      METHOD: The Radial Artery Patency and Clinical Outcomes (RAPCO) trial is a double
      armed randomized controlled trial comparing the RA with the free RITA in a
      younger cohort of patients undergoing elective coronary bypass surgery, and the
      RA with the saphenous vein in an older group. The trial conduit was grafted to
      the most important coronary target after the left anterior descending artery,
      which received the gold standard left internal thoracic artery. Clinical outcomes
      and angiographic patency up to 10 years was recorded during careful follow up,
      with annual clinical review and a program of randomly assigned, staggered
      angiography. The final trial results will be available in 2014. RESULTS: Mid
      trial results have shown equivalent survival and event-free survival and graft
      patency in both arms at median follow up of approximately 6 years. The
      demographic and clinical data, pre- and postoperative angiographic findings of
      the trial database have led to a number of substudies focusing on the role of
      lipid exposure in patency and disease progression, the fate of moderate lesions
      when grafted or left alone, patterns of disease regression, and patient
      satisfaction with graft harvest sites. CONCLUSIONS: While the final analysis of
      the primary trial end points is eagerly awaited, the additional insight into the
      natural history of grafted coronary artery disease with modern secondary
      prevention will be of considerable interest.

PMID- 23977624
TI  - Improved late survival with arterial revascularization.
AB  - NEW CORONARY ARTERY REVASCULARIZATION STRATEGIES ARE DEVELOPING: improved
      quantification of coronary artery disease by the SYNTAX score, new-generation
      drug-eluting stents and increased use of stents for multivessel disease, ongoing
      evaluation of stents for left main disease, new strategies for minimally invasive
      coronary artery bypass grafting (CABG) including the use of robotic-assisted
      CABG, hybrid procedures, and off pump CABG. In comparisons of all these
      strategies, the impact on survival is arguably the most important parameter. It
      has long been accepted that using the left internal mammary artery (LIMA) to
      bypass the left anterior descending coronary artery (LAD) is the gold standard
      and may confer the survival advantage reported for CABG compared with
      percutaneous coronary intervention in the literature. The survival advantage of
      using additional arterial conduits as compared to the conventional use of LIMA
      with saphenous veins only has long been debated. Our study, which involved a
      large cohort of 8,622 patients with multivessel disease, followed over a long
      period of time, has shown that in primary isolated CABG surgery performed more
      than 15 years ago with the use of LIMA to the LAD, bypassing the non-LAD targets
      with at least 1 additional arterial graft, either the right internal mammary
      artery and/or the radial artery, was an independent predictor of increased
      survival during the following 15 years. The results were confirmed with both a
      propensity-matched analysis that included 1,153 patients in each group and a
      multivariate analysis that was able to control for all differences between the
      groups because of the power of the large cohort in this series. The significant
      survival advantage of coronary artery bypass surgery with the use of multiple
      arterial grafting cannot be ignored in patients with multivessel coronary artery
      disease as various revascularization strategies are considered.

PMID- 23977625
TI  - Importance of the third arterial graft in multiple arterial grafting strategies.
AB  - BACKGROUND: The long-term benefit of multiple arterial grafts for coronary artery
      bypass (CABG) is not clear. This protocol was elaborated to see if multiple
      arterial grafts would provide better long-term outcomes when compared with
      conventional strategies. METHODS: Prospective data was collected for 588 patients
      undergoing isolated CABG between 1985 and 1995. We analyzed long term survival
      and freedom from cardiac death. The analysis compared patients with BITA grafting
      receiving a right gastro-epiploic artery (RGEA) versus those receiving a
      saphenous vein graft (SVG) as a third conduit. Cox proportional hazards modelling
      was used to adjust for relevant confounders. RESULTS: The mean age was 59+/-9
      years and 49% received BITA. Mean follow-up was 16.1+/-5.4 years. Multivariable
      analysis revealed in that patients receiving the RGEA as a third conduit had
      superior overall survival (HR, 0.46; P=0.015) and cardiac survival (HR, 0.20;
      P=0.005) compared to those receiving an SVG. CONCLUSIONS: In our experience, the
      use of multiple arterial grafting is independently associated with superior
      outcomes. Furthermore, the use of a third arterial conduit targeted to the RCA
      should be considered to improve long-term survival.

PMID- 23977626
TI  - Twenty-year fate of the radial artery graft.
AB  - It is well known that radial arteries (RA) are not the primary choice as coronary
      artery grafts. In this Research Highlight, we discuss the follow-up results of
      629 radial artery grafts performed over 20 years. Focal stenosis occurred in 3%
      of RAs, while string signs were observed in 0.9%. Overall graft patency was 83%,
      but indication for angiographic assessment was driven by symptomatic
      presentation. Graft patency decreased exponentially during the first
      postoperative year, but patency rate declined at a linear rate with low attrition
      afterwards, suggesting a lack of radial graft disease. These results indicate
      relatively stable radial artery patency rates for up to 20 years. 

PMID- 23977628
TI  - Gastroepiploic artery graft in coronary artery bypass grafting.
AB  - The right gastroepiploic artery (GEA) has been recognized as a suitable and
      reliable conduit for coronary bypass surgery. From a sizable number of
      experiences, we know the use of this artery does not increase surgical risk, and
      no gastric ischemia nor abdominal complications occur with takedown of the GEA.
      This artery undergoes less significant arteriosclerosis and demonstrates
      physiological adaptability as seen in the internal thoracic artery (ITA). From
      our experience with over 1,500 GEA grafts, the operative mortality was 1.26%, and
      5-, 10-, and 15-year survival rates were 91.7%, 81.4%, and 71.3% respectively,
      while the cardiac death-free survival rates were 95.8%, 91.7%, and 88.6%,
      respectively. The cumulative patency rate of the GEA graft was 98.5% at 1 month,
      93.7% at 1 year, 86.2% at 5 years, and 70.2% at 10 years. The GEA graft is a safe
      and effective arterial conduit for coronary artery bypass grafting (CABG). 

PMID- 23977627
TI  - Bilateral internal thoracic artery grafting.
AB  - The effectiveness of the left internal mammary artery graft to the anterior
      descending coronary artery as a surgical strategy has been shown to improve the
      survival rate and decrease the risk of adverse cardiac events in patients
      undergoing coronary bypass surgery. These clinical benefits appear to be related
      to the superior short and long-term patency rates of the internal thoracic artery
      graft. Although the advantages of using of both internal thoracic arteries (ITA)
      for bypass grafting have taken longer to prove, recent results from multiple data
      sets now support these findings. The major advantage of bilateral ITA grafting
      appears to be improved survival rate, while the disadvantages of complex ITA
      grafting include the increased complexity of operation, and an increased risk of
      wound complications. While these short-term disadvantages have been mitigated in
      contemporary surgical practice, they have not eliminated. Bilateral ITA grafting
      should be considered the procedure of choice for patients undergoing coronary
      bypass surgery that have a predicted survival rate of longer than ten years. 

PMID- 23977629
TI  - Total arterial coronary revascularization-patient selection, stenoses, conduits,
      targets.
AB  - Graft patency determines prognosis in coronary artery bypass grafting (CABG).
      Numerous reports over the past 20 years have documented superior patencies and
      prognosis when multiple arterial grafts are used, yet less than 10% of CABG have
      multiple arterial grafts. Several conduits have been proposed, with varying
      degrees of success. Saphenous vein grafts (SVG) begin to fail with intimal
      hypertrophy and then atheroma after 5 years, with patency rates of 50% to 60% at
      10 years, and <30% at 15 years. In contrast, left internal thoracic artery (LITA)
      patency is >95% at 10 years and >90% at 20 years. The radial artery is extremely
      versatile and can reach all territories, but is muscular and vulnerable to spasm
      and competitive flow. Similarly, the right gastroepiploic artery is also
      muscular, and is best suited to the posterior descending coronary artery,
      especially in reoperations and is also affected by competitive flow. In addition,
      bilateral internal thoracic artery grafting (BITA) grafts and total arterial
      revascularization (TACR) can be performed with identical perioperative mortality
      (1%) and perioperative morbidity to LITA + SVG. Importantly, survival is superior
      85% to 90% at 10 years versus 75% to 80% respectively. BITA/TACR patients also
      suffer fewer late cardiac events and reoperations, with superior results for
      older patients, those requiring urgent surgery, diabetics, patients with renal
      dysfunction and in reoperations. Contraindications to BITA include obesity,
      insulin dependent diabetics, and severe chronic obstructive airways disease. As
      such, arterial grafts have better patencies and clinical results. BITA/TACR is
      often underutilized, but can be achieved in the majority of patients.
      Opportunities exist to enhance BITA/TACR use in CABG to the potential benefit of
      our patients. 

PMID- 23977631
TI  - Why is the mammary artery so special and what protects it from atherosclerosis?
AB  - The internal mammary artery (IMA) grafts have been associated with long-term
      patency and improved survival as compared to saphenous vein grafts (SVGs). Early
      failure of IMA is attributed to poor surgical technique and less with thrombosis.
      Similarly, bypass surgery especially with the use of IMA has also been shown to
      be superior at 1-year as well as over five years compared to percutaneous
      procedures, including the use of drug-eluting stents for the treatment of
      coronary artery disease. The superiority of IMAs over SVGs can be attributed to
      its striking resistance to the development of atherosclerosis. Structurally its
      endothelial layer shows fewer fenestrations, lower intercellular junction
      permeability, greater anti-thrombotic molecules such as heparin sulfate and
      tissue plasminogen activator, and higher endothelial nitric oxide production,
      which are some of the unique ways that make the IMA impervious to the transfer of
      lipoproteins, which are responsible for the development of atherosclerosis. A
      better comprehension of the molecular resistance to the generation of adhesion
      molecules that are involved in the transfer of inflammatory cells into the
      arterial wall that also induce smooth muscle cell proliferation is needed. This
      basic understanding is crucial to championing the use of IMA as the first line of
      defense for the treatment of coronary artery disease. 

PMID- 23977630
TI  - Arterial grafts: clinical classification and pharmacological management.
AB  - In comparison with standard saphenous vein grafts, use of the internal mammary
      artery (IMA) as a coronary artery bypass graft has achieved superior long-term
      results. This is related to the differences in the biological characteristics
      between the venous and arterial grafts. However, even arterial grafts are not
      uniform in their biological characteristics. The variation in the perioperative
      behavior of the grafts and in their long-term patency may be related to different
      characteristics. These factors should be taken into account in the use of
      arterial grafts, some of which are subjected to more active pharmacological
      intervention during and after the operation to obtain satisfactory results. To
      better understand the biological behavior of the grafts, their common features
      and their differences, a clinical classification may be useful for a practicing
      surgeon. Based on experimental studies of their vasoreactivity combined with
      anatomical, physiological and embryological considerations, we have proposed a
      functional classification for arterial grafts that may be useful clinically. Our
      classification suggests that there are three types of arterial grafts: Type I
      somatic arteries; Type II-splanchnic arteries; and Type III-limb arteries. Type I
      arteries have enhanced endothelial function and release more nitric oxide and
      other relaxing factors. Type II arteries, such as the gastro-epiploic artery, and
      Type III arteries, such as the radial artery (RA), have higher pharmacological
      reactivity to vasoconstrictors. This classification explains why the IMA has the
      best long-term patency. Because Type II and III arteries are prone to spasms due
      to higher contractility, they require more active pharmacological interventions.
      Furthermore, the harvesting technique of the conduits, including the saphenous
      vein and IMA, are described and discussed in this article. Prevention of spasms
      using two cocktails of medications (verapamil + nitroglycerin and nicardipine +
      nitroglycerin) during harvesting of the conduits is described. These solutions
      have been demonstrated to be clinically effective. 

PMID- 23977633
TI  - Harvesting the radial artery.
AB  - The radial artery (RA) has emerged as an important arterial graft for coronary
      bypass surgery. With improving five-year patency rates and increasing uptake,
      great attention has been focused on the optimal conduit harvesting technique. We
      herein present our approach to RA harvesting. Prerequisites of a successful
      harvest include adherence to important anatomical landmarks, protection of the
      sensory innervation to the volar forearm, and meticulous handling of the RA
      branches. Regardless of the harvesting methodology chosen, adherence to a "no
      touch" technique will optimize the patency and durability of the RA conduit. 

PMID- 23977632
TI  - How I choose conduits and configure grafts for my patients-rationales and
      practices.
AB  - Coronary artery bypass grafting (CABG) continues to be an effective therapy for
      many patients with lasting long-term durability and consistent outcomes, despite
      the development of percutaneous revascularization. The long-term outcome for
      surgical revascularization depends on multiple variables, including the choice of
      conduits. However, the choice of coronary conduits has been studied and debated
      for decades now. In this review article, we examined the current evidences and
      described our choice on coronary conduits and grafting strategies at our medical
      center. 

PMID- 23977634
TI  - The art of arterial revascularization-total arterial revascularization in
      patients with triple vessel coronary artery disease.
AB  - The use of the left internal thoracic artery to graft the left anterior
      descending artery has been widely accepted as the gold standard for surgical
      treatment of coronary disease for over 40 years. However the use of multiple
      other arterial grafts to support this has not been accepted readily, in spite of
      evidence of superiority over saphenous vein grafts, probably because of
      perceptions of technical complexity, time constraints for conduit harvesting and
      increased peri-operative complications. As a result, even today most patients
      with multivessel coronary artery disease do not receive the potential benefits of
      extensive or total arterial revascularization. We discuss here the use of
      contemporary techniques and grafts configurations to simplify this, and the
      safety and benefit data underpinning this practice. Current patency data confirm
      that a left internal thoracic artery graft performs well beyond 20 years, with
      over 80% freedom from failure, but accumulating data suggest that the right
      internal thoracic artery behaves in the same way. Radial artery grafts are being
      studied in several randomized trials, but observational studies already suggest a
      performance which compares favourably with saphenous vein. Total arterial
      revascularization is achievable in most patients with a small but acceptable
      increase in risk of sternal complications when certain defined subgroups are
      excluded. 

PMID- 23977635
TI  - Off-pump coronary artery bypass grafting using skeletonized in situ arterial
      grafts.
AB  - Skeletonization is an advanced technique of graft harvesting for coronary artery
      bypass grafting (CABG), and while it requires meticulous attention, it has many
      advantages. For example, skeletonization of internal thoracic artery (ITA) can
      minimize sternal ischemia and lower the risk of mediastinitis, and is longer and
      larger than pedicled ITA. In this article we describe the surgical techniques
      demonstrated in our video, which details our techniques of skeletonization of
      arterial grafts and off-pump coronary artery bypass (OPCAB) exclusively using
      these in situ grafts. Our method of right gastroepiploic artery (GEA)
      skeletonization has only three technical steps. The first step is to pass thin
      vessel loops under the GEA. The second step is to unroof the tissue surrounding
      the GEA. The last step is to seal and sever all the branches. Skeletonization of
      the GEA not only prevents vasospasm but also leads to GEA dilatation, and
      facilitates inspection and makes sequential anastomosis easier. Bilateral use of
      the skeletonized ITA and use of the skeletonized GEA can cover most coronary
      artery target sites without any manipulation of the ascending aorta. In our
      consecutive series of over 1,000 patients, the stroke rate was 0.5%. Our method
      helps to make the technique simple and secure in this technically demanding
      operation, and we believe that OPCAB with these grafts provides the best possible
      coronary revascularization. 

PMID- 23977636
TI  - Endoscopic radial artery harvesting procedure for coronary artery bypass
      grafting.
AB  - Development and adoption of endoscopic minimally invasive saphenous vein
      harvesting prompted its application to the radial artery in an effort to minimize
      surgical trauma. Recently, we reported that endoscopic radial artery harvesting
      was associated with better wound appearance and it proved to be safe and
      effective, with less pain and fewer wound complications than the open surgical
      technique. Based on this positive experience, our institution adopted endoscopic
      radial artery harvesting, hence the aim of this manuscript is to describe the
      minimally invasive endoscopic radial artery harvesting for coronary artery bypass
      grafting. 

PMID- 23977637
TI  - Endoscopic harvesting of the left internal mammary artery.
AB  - Minimally invasive coronary artery bypass grafting via left anterior small
      thoracotomy is routinely performed on patients with single coronary artery
      disease, but recently has been expanded to a larger population as a part of a
      hybrid treatment in multivessel coronary artery disease. While the methods of
      internal mammary artery harvesting used in these operations can be different, the
      endoscopic method is more advantageous than operations performed by direct
      vision, and thus should be used as a technique of choice. In this article, we
      present detailed description of endoscopic mammary artery harvesting focusing on
      anatomical and technical aspects. 

PMID- 23977638
TI  - Bilateral internal mammary arteries: evidence and technical considerations.
AB  - Bilateral internal mammary artery (BIMA) grafts are used for coronary
      revascularisation by only a minority of surgeons, despite a growing body of
      evidence suggesting improved survival when compared to use of only one internal
      mammary artery with additional saphenous vein grafts. Herein we review the
      evidence supporting revascularisation with BIMA and suggest reasons why the
      majority of surgeons use only one internal mammary artery. We discuss technical
      considerations, various graft combinations and the use of BIMA to facilitate
      anaortic off-pump coronary artery bypass (OPCAB). 

PMID- 23977639
TI  - Systematic review protocol: the frozen elephant trunk approach in aortic arch
      surgery.
AB  - BACKGROUND: Surgical management of aortic arch pathologies still faces
      significant challenges, especially if the pathology involves the proximal
      descending aorta. A novel solution, named the frozen elephant trunk approach,
      encompasses a hybrid stent-graft that is placed during conventional arch surgery
      in the descending aorta to exert an expansive radial force. This obviates the
      need for second-stage surgery, while limiting the residual patency of the false
      lumen and minimizing wall stress. The objective of this systematic review is to
      assess the safety and efficacy of the frozen elephant trunk technique in aortic
      ach pathologies. SELECTION CRITERIA: We included all studies that used hybrid
      stent grafts, or stented the proximal descending aorta under direct visualization
      during conventional arch surgery. Six electronic databases were searched
      (inception to June 2013), limited to studies that have reported 10 patients or
      more in the English language. MAIN RESULTS: Sixteen observational studies, with
      1,409 patients, were identified. A variety of commercial and custom-made stent
      grafts were used, with varying pathology indications. Overall mortality was 8.5%
      (range, 0-18.2%). One-year survival, reported in six studies, was 85.6% (range,
      70-97%), while five-year survival was 71.5% (range, 63-88%). Stroke and spinal
      cord injury was identified in 5.3% and 5.5% of patients respectively, while renal
      failure and reoperation for bleeding was 12.0% and 8.9% respectively. No other
      endpoints were sufficiently reported. IMPLICATIONS FOR CLINICAL PRACTICE: The
      frozen elephant trunk approach represents a reasonably safe procedure to repair
      the arch and proximal descending aorta. While promising, these results require
      long-term studies to assess durability and freedom from reoperation. Further
      regulatory approval is also required to permit widespread employment of
      specialized commercial hybrid stent-grafts.

PMID- 23977640
TI  - Coronary artery bypass grafting.

PMID- 23977641
TI  - Community-based participatory research projects and policy engagement to protect
      environmental health on St Lawrence Island, Alaska.
AB  - OBJECTIVES: This article synthesizes discussion of collaborative research
      results, interventions and policy engagement for St Lawrence Island (SLI),
      Alaska, during the years 2000-2012. METHODS: As part of on-going community-based
      participatory research (CBPR) studies on SLI, 5 discrete exposure-assessment
      projects were conducted: (a) a biomonitoring study of human blood serum; (b-d) 3
      investigations of levels of contaminants in environmental media at an abandoned
      military site at Northeast Cape--using sediment cores and plants, semi-permeable
      membrane devices and blackfish, respectively; and (e) a study of traditional
      foods. RESULTS: Blood serum in residents of SLI showed elevated levels of
      polychlorinated biphenyls (PCBs) with higher levels among those exposed to the
      military site at Northeast Cape, an important traditional subsistence-use area.
      Environmental studies at the military site demonstrated that the site is a
      continuing source of PCBs to a major watershed, and that clean-up operations at
      the military site generated PCB-contaminated dust on plants in the region.
      Important traditional foods eaten by the people of SLI showed elevated
      concentrations of PCBs, which are primarily derived from the long-range transport
      of persistent pollutants that are transported by atmospheric and marine currents
      from more southerly latitudes to the north. INTERVENTIONS: An important task for
      all CBPR projects is to conduct intervention strategies as needed in response to
      research results. Because of the findings of the CBPR projects on SLI, the CBPR
      team and the people of the Island are actively engaging in interventions to
      ensure cleanup of the formerly used military sites; reform chemicals policy on a
      national level; and eliminate persistent pollutants internationally. The goal is
      to make the Island and other northern/Arctic communities safe for themselves and
      future generations. CONCLUSIONS: As part of the CBPR projects conducted from 2000
      to 2012, a series of exposure assessments demonstrate that the leaders of SLI
      have reason to be concerned about the health of people due to the presence of
      carcinogenic chemicals as measured in biomonitoring and environmental samples and
      important traditional foods.

PMID- 23977642
TI  - Patient and provider perspectives on using telemedicine for chronic disease
      management among Native Hawaiian and Alaska Native people.
AB  - BACKGROUND: Among indigenous populations in remote locations who are at increased
      risk for chronic diseases such as diabetes, telemedicine has the potential to
      improve access to health care services and thus may reduce adverse health
      outcomes. Yet few studies are available on how best to use telemedicine
      technology in reducing ethnic and racial health care disparities. OBJECTIVE: We
      examined perspectives of patients and providers in 2 indigenous populations in
      Alaska and Hawai'i about the use of telemedicine in primary care chronic disease
      management. DESIGN: Six focus groups with patients and providers at 2 sites (3 in
      Alaska and 3 in Hawai'i). RESULTS: Three broad themes were common to both sites:
      (a) benefits and barriers of using telemedicine; (b) building patient-provider
      relationships; and (c) elements of an acceptable telemedicine primary care
      encounter. Two key elements were endorsed by both patients and providers as
      important for an effective telemedicine encounter: (a) the initial patient
      provider interaction should be face-to-face; and (b) patients must see the same
      provider on follow-up visits. CONCLUSION: The use of telemedicine in chronic
      disease management has potential to improve patient care in remote indigenous
      populations and may supplement patient-provider relationships.

PMID- 23977643
TI  - Mortality trends among Alaska Native people: successes and challenges.
AB  - BACKGROUND: Current mortality rates are essential for monitoring, understanding
      and developing policy for a population's health. Disease-specific Alaska Native
      mortality rates have been undergoing change. OBJECTIVE: This article reports
      recent mortality data (2004-2008) for Alaska Native/American Indian (AN/AI)
      people, comparing mortality rates to US white rates and examines changes in
      mortality patterns since 1980. DESIGN: We used death record data from the state
      of Alaska, Department of Vital Statistics and SEER*Stat software from the
      National Cancer Institute to calculate age-adjusted mortality rates. RESULTS:
      Annual age-adjusted mortality from all-causes for AN/AI persons during the period
      2004-2008 was 33% higher than the rate for US whites (RR = 1.33, 95% CI 1.29
      1.38). Mortality rates were higher among AN/AI males than AN/AI females
      (1212/100,000 vs. 886/100,000). Cancer remained the leading cause of death among
      AN/AI people, as it has in recent previous periods, with an age-adjusted rate of
      226/100,000, yielding a rate ratio (RR) of 1.24 compared to US whites (95% CI
      1.14-1.33). Statistically significant higher mortality compared to US white
      mortality rates was observed for nine of the ten leading causes of AN/AI
      mortality (cancer, unintentional injury, suicide, alcohol abuse, chronic
      obstructive pulmonary disease [COPD], cerebrovascular disease, chronic liver
      disease, pneumonia/influenza, homicide). Mortality rates were significantly lower
      among AN/AI people compared to US whites for heart disease (RR = 0.82), the
      second leading cause of death. Among leading causes of death for AN/AI people,
      the greatest disparities in mortality rates with US whites were observed in
      unintentional injuries (RR = 2.45) and suicide (RR = 3.53). All-cause AN/AI
      mortality has declined 16% since 1980-1983, compared to a 21% decline over a
      similar period among US whites. CONCLUSION: Mortality rates and trends are
      essential to understanding the health of a population and guiding policy
      decisions. The overall AN/AI mortality rate is higher than that of US whites,
      although encouraging declines in mortality have occurred for many cause specific
      deaths, as well as for the overall rate. The second leading cause of AN/AI
      mortality, heart disease, remains lower than that of US whites.

PMID- 23977644
TI  - The State of Alaska's early experience with institutionalization of health impact
      assessment.
AB  - BACKGROUND: Many nations routinely include health impact assessments (HIA) in
      public policy decisions. Institutionalization of HIA formally integrates health
      considerations into a governmental decision-making process. We describe an
      example of institutionalization in the United States through Alaska's early
      experience with institutionalization of HIA. LITERATURE REVIEW: HIA arose from a
      series of health conferences in the 1970s that affirmed the importance of "health
      for all." A number of key milestones eventually defined HIA as a unique field of
      impact assessment. There are several approaches to institutionalization, and one
      common approach in the United States is through the National Environmental Policy
      Act (NEPA). NEPA formed the basis for the earliest HIAs in Alaska. PROGRAM
      DESCRIPTION: Early HIAs in Alaska led to conferences, working groups, a state
      guidance document and the institutionalization of a HIA program within the
      Department of Health and Social Services in 2010. A medical epidemiologist staffs
      the program, which utilizes contractors to meet rising demand for HIA. The HIA
      program has sustainable funding from the state budget and from the state's
      natural resource permitting process. The HIA document is the main deliverable,
      but the program performs other tasks, including fieldwork and technical reviews.
      The HIA program works closely with a host of collaborative partners. CONCLUSION:
      Alaska's institutionalized HIA program benefits from sustainable funding that
      promotes continuous quality improvement and involves the program in the entire
      life cycle of a development project. The program structure adapts well to
      variations in workflow and supports a host of quality control activities.
      Currently, the program focuses on HIAs for natural resource development projects.

PMID- 23977645
TI  - Doing the right thing! A model for building a successful hospital-based ethics
      committee in Nunavut.
AB  - BACKGROUND: There exists a need throughout the North to increase capacity to
      address issues of health ethics and for community members to better understand
      and share their perspectives on this topic. Ethics comes down to weighing rights
      and wrongs, evaluating differing needs and understandings, acknowledging the many
      shades of grey and doing our best to come up with the just, fair and moral
      approach to the question at hand. Northern regions must collaborate to share
      capacity, successes and experiences in order to meet the unique needs of northern
      health care institutions and move forward on this issue. While guidelines for
      ethical research with indigenous populations exist, little has been published
      about an Inuit approach to health ethics more broadly. DESIGN: To fill a critical
      need and to meet accreditation standards, the Qikiqtani General Hospital (QGH) in
      Iqaluit, Nunavut, Canada, is in the process of building an Ethics Committee.
      Capitalizing on partnerships with other bodies both in northern and southern
      Canada has proved an efficient and effective way to develop local solutions to
      challenges that have been experienced both at QGH and other jurisdictions.
      METHODS: The Ottawa Hospital Ethics Office and the active ethics committee at
      Stanton General Hospital in Yellowknife, NT, contributed expertise and
      experience, and helped provide some direction for the QGH ethics committee. At
      the local level, based on our shared commitment to health care ethics, the
      Qaujigiartiit Health Research Centre is an invaluable partner whose parallel
      efforts to develop a northern Health Research Ethics Board (REB) gives great
      synergy to the QGH Ethics Committee. RESULTS: Passion and commitment, as well as
      administrative support and endorsement from health care leaders, are the aspects
      of successful initiatives that we have identified to date. Using the information
      from both the experiences of other partners, as well as information gathered at a
      retreat held in Iqaluit in September 2011, we are working to develop a model for
      the QGH ethics committee that incorporates multi-level perspectives, from that of
      community to that of front-line worker. CONCLUSION: Ideally, the scope of the QGH
      Ethics Committee will grow over time to include ethics education, facilitation of
      clinical ethical consults, ethical review of policy, advice on governance issues
      and involvement and support of an external northern Health REB.

PMID- 23977646
TI  - Consultation and remediation in the north: meeting international commitments to
      safeguard health and well-being.
AB  - BACKGROUND: International commitments exist for the safeguarding of health and
      the prevention of ill health. One of the earliest commitments is the Declaration
      of Alma-Ata (1978), which provides 5 principles guiding primary health care:
      equity, community participation, health promotion, intersectoral collaboration
      and appropriate technology. These broadly applicable international commitments
      are premised on the World Health Organization's multifaceted definition of
      health. The environment is one sector in which these commitments to safeguarding
      health can be applied. Giant Mine, a contaminated former gold mine in the
      Northwest Territories, Canada, represents potential threats to all aspects of
      health. Strategies for managing such threats usually involve an obligation to
      engage the affected communities through consultation. OBJECTIVE: To examine the
      remediation and consultation process associated with Giant Mine within the
      context of commitments to safeguard health and well-being through adapting and
      applying the principles of primary health care. METHODS: Semi-structured
      interviews with purposively selected key informants representing government
      proponents and community members were conducted. RESULTS: in reviewing themes
      which emerged from a series of interviews exploring the community consultation
      process for the remediation of Giant Mine, the principles guiding primary health
      were mapped to CONSULTATION IN the North: (a) "equity" is the capacity to fairly
      and meaningfully participate in the consultation; (b) "community participation"
      is the right to engage in the process through reciprocal dialogue; (c) "health
      promotion" represents the need for continued information sharing towards
      awareness; (d) "intersectoral collaboration" signifies the importance of
      including all stakeholders; and (e) "appropriate technology" is the need to
      employ the best remediation actions relevant to the site and the community.
      CONCLUSIONS: Within the context of mining remediation, these principles form an
      appropriate framework for viewing consultation as a means of meeting
      international obligations to safeguard health.

PMID- 23977647
TI  - The antioxidant level of Alaska's wild berries: high, higher and highest.
AB  - BACKGROUND: In the last few years, antioxidants have become the stars of the
      nutritional world. Antioxidants are important in terms of their ability to
      protect against oxidative cell damage that can lead to conditions, such as
      Alzheimer's disease, cancer and heart disease--conditions also linked with
      chronic inflammation. The antioxidant and anti-inflammatory effects of Alaska's
      wild berries may have the potential to help prevent these diseases. OBJECTIVE: To
      discover the antioxidant levels of Alaska wild berries and the ways these
      antioxidant levels translate when preservation methods are applied to the berry.
      DESIGN: This research centred on both the raw berries and products made from the
      berries. In the first year, a variety of wild berries were tested to discover
      their oxygen radical absorption capacity (ORAC) in the raw berries. The second
      level of the research project processed 4 different berries--blueberries,
      lingonberries, salmonberries, highbush cranberries--into 8 or 9 products made
      from these berries. The products were tested for both ORAC as well as specific
      antioxidants. RESULTS: The Alaska wild berries collected and tested in the first
      experiment ranged from 3 to 5 times higher in ORAC value than cultivated berries
      from the lower 48 states. For instance, cultivated blueberries have an ORAC scale
      of 30. Alaska wild dwarf blueberries measure 85. This is also higher than lower
      48 wild blueberries, which had a score of 61. All of the Alaskan berries tested
      have a level of antioxidant considered nutritionally valuable, ranging from 19
      for watermelon berries to 206 for lingonberries on the ORAC scale. With the
      processed products made from 4 Alaska wild berries, one of the unexpected
      outcomes of the research was that the berries continued to have levels of
      antioxidants considered high, despite the effects of commonly used heat
      processing techniques. When berries were dehydrated, per gram ORAC values
      increased. CONCLUSION: Alaska wild berries have extraordinarily high antioxidant
      levels. Though cooking lowered the antioxidant level, and adding ingredients such
      as sugar diluted the antioxidant concentration, products made from berries are
      high sources of antioxidants.

PMID- 23977648
TI  - Informal and formal mental health: preliminary qualitative findings.
AB  - BACKGROUND: Northern-based research on mental health support, no matter the
      specific profession, helps to inform instruction of new practitioners and
      practitioners already working in rural or isolated conditions. Understanding the
      complexities of northern mental health support not only benefits clients and
      practitioners living in the North, but also helps prepare psychologists and
      counsellors preparing to work in other countries with large rural and isolated
      populations. The qualitative phase is part of a multi-year research study on
      informal and formal mental health support in northern Canada involving the use of
      qualitative and quantitative data collection and analysis methods. OBJECTIVE: The
      main objective of the qualitative phase interviews was to document in-depth the
      situation of formal and informal helpers in providing mental health support in
      isolated northern communities in northern British Columbia, northern Alberta,
      Yukon and Northwest Territories (NWT). The intent of in-depth interviews was to
      collect descriptive information on the unique working conditions of northern
      helping practitioners for the development of a survey and subsequent community
      action plans for helping practitioner support. DESIGN: Twenty participants in
      northern BC, Yukon and NWT participated in narrative interviews. Consensual
      qualitative research (CQR) was used in the analysis completed by 7 researchers.
      The principal researcher and research associate then worked through all 7
      analyses, defining common categories and themes, and using selections from each
      researcher in order to ensure that everyone's analysis was represented in the
      final consensual summary. RESULTS: The preliminary results include 7 main
      categories consisting of various themes. Defining elements of northern practice
      included the need for generalist knowledge and cultural sensitivity. The task of
      working with and negotiating membership in community was identified as essential
      for northern mental health support. The need for revised codes of ethics relevant
      to the reality of northern work was a major category, as was insight on how to
      best sustain northern practice. CONCLUSION: Many of the practitioners who
      participated in this study have found ways to overcome the biggest challenges of
      northern practice, yet the limitations of small populations and lack of resources
      in small communities to adequately address mental health support were identified
      as existing. Empowering communities by building community capacity to educate,
      supervise and support formal and informal mental health workers may be the best
      approach to overcoming the lack of external resources.

PMID- 23977649
TI  - Design, formulation and evaluation of a mucoadhesive gel from Quercus brantii L.
      and coriandrum sativum L. as periodontal drug delivery.
AB  - BACKGROUND: Periodontitis is inflammation of the supporting tissues of the teeth
      caused by specific microorganisms. Intra-periodontal pocket, mucoadhesive drug
      delivery systems have been shown to be clinically effective in the treatment of
      periodontitis. The aim of this study was to formulate a mucoadhesive gel from the
      seed hull of Quercus brantii and fruits of Coriandrum sativum for the treatment
      of periodontitis. MATERIALS AND METHODS: The semisolid concentrated extracts were
      incorporated in gel base. Mucoadhesive gels were prepared using carbopol 940,
      sodium carboxymethylcellulose (sodium CMC) and hydroxypropyl methylcellulose K4M
      (HPMC) as bioadhesive polymers. Physicochemical tests, mucoadhesive strength
      measurement and in vitro drug release study were carried out on two formulations
      containing carbopol 940 and sodium CMC polymers (Formulations F4 and F5). We
      investigated the antibacterial activity of formulation F5 against Porphyromonas
      gingivalis using the disk diffusion method on supplemented Brucella agar.
      RESULTS: Eight gel formulations were prepared. Physical appearance, homogeneity
      and consistency of F4 and F5 were good. Mucoadhesion and viscosity of F5 (1%
      carbopol 940 and 3% sodium CMC) was more than F4 (0.5% carbopol 940 and 3% sodium
      CMC). Drug release from F5 was slower. Both of formulations were syringeable
      through 21 G needle. In the disk diffusion method, F5 produced significant growth
      inhibition zones against P. gingivalis. CONCLUSION: The ideal formulation for the
      treatment of periodontitis should exhibit high value of mucoadhesion, show
      controlled release of drug and be easily delivered into the periodontal pocket
      preferably using a syringe. Based on in vitro release and mucoadhesion studies,
      F5 was selected as the best formulation.

PMID- 23977650
TI  - The role of pelvic organs prolapse in the etiology of urinary incontinence in
      women.
AB  - BACKGROUND: Urinary incontinence is relatively common in women and is usually
      associated with pelvic organs prolapse. Our aim was to determine the relationship
      between type and intensity of urinary incontinence and different grades and types
      of pelvic organ prolapse among women. MATERIALS AND METHODS: One-hundred female
      patients with the chief complaint of incontinence, who were diagnosed with pelvic
      organ prolapse participated in this study. Intensity of prolapse, stress and urge
      incontinence were evaluated using POP-Q (Pelvic Organ Prolapse Questionnaire),
      SEAPI (Stress related, Emptying ability, Anatomy, Protection, Inhibition) and
      Freeman criteria, respectively. RESULTS: Patients' mean age was 51.95 +/- 12.82
      years. The most common type of incontinence was stress incontinence (53%) and the
      most common prolapse type was cystocele (76%). Cystocele and rectocele had a
      significant relationship with stress (P value = 0.012) and urge incontinence (P
      value = 0.035), respectively; however, no relationship was observed between
      different grades of cystocele, rectocele and enterocele with different types of
      urinary incontinence (P value > 0.05). In patients with urge and mixed
      incontinence, prolapse grade significantly increased with age, but no such
      relationship was found in patients with stress incontinence. The number of
      vaginal deliveries had a significant relationship only with cystocele and
      rectocele grade; however, the relationship between other variables such as
      intensity of different types of urinary incontinence and enterocele grade with
      the number of deliveries was not significant. CONCLUSION: Pelvic organ prolapse
      had a significant relationship with urinary incontinence regardless of intensity
      and POP should be examined in all of these patients.

PMID- 23977651
TI  - Detection of methicillin-resistance gene in Staphylococcus epidermidis strains
      isolated from patients in Al-Zahra Hospital using polymerase chain reaction and
      minimum inhibitory concentration methods.
AB  - BACKGROUND: In recent years, antibiotic resistance of Staphylococcus epidermidis
      to methicillin has significantly increased, making it essential to study
      resistance to methicillin, which is a determining factor in the appropriate
      treatment pattern. The purpose of this study was to identify methicillin
      resistant genes in S. epidermidis strains using polymerase chain reaction (PCR)
      and to determine their mean minimum inhibitory concentration (MIC) to methicillin
      using E-test method. MATERIALS AND METHODS: MIC was determined on 146 samples of
      S. epidermidis using E-test method. Moreover, all samples were tested for the
      presence of mecA gene using PCR. RESULTS: PCR test showed 75.34% of the samples
      to contain mecA gene. Methicillin resistance test was performed using E-test on
      all the samples, which showed resistance in different dilutions. CONCLUSION: The
      frequency of mecA gene in S. epidermidis isolates was 75.34%. Among the various
      applied tests used for determining methicillin resistance, sensitivity and
      specificity of PCR were the highest and reached 100%. Sensitivity and specificity
      were found to be 95.3% and 94.7%, respectively, for phenotypic test (E-test) and
      86.5% and 80.9%, respectively, for disk diffusion method. Based on the above
      results, it seems that resistance of S. epidermidis to methicillin is on the
      rise, and therefore more research is warranted.

PMID- 23977652
TI  - The effect of CTB on P53 protein acetylation and consequence apoptosis on MCF-7
      and MRC-5 cell lines.
AB  - BACKGROUND: P300 is a member of the mammalian histone acetyl transferase (HAT)
      family, an enzyme that acetylates histones and several non-histone proteins
      including P53 (the most important tumor suppressor gene) during stress, which
      plays an important role in the apoptosis of tumor cells. Hereby, this study
      describes the potency of CTB (Cholera Toxin B subunit) as a P300 activator to
      induce apoptosis in a breast cancer cell line (MCF-7) and a lung fibroblast cell
      line (MRC-5) as a non-tumorigenic control sample. MATERIALS AND METHODS: MCF-7
      and MRC-5 were cultured in RPMI-1640 and treated with or without CTB at a
      concentration of 85.43 MUmol/L, based on half-maximal inhibitory concentration
      (IC50) index at different times (24, 48 and 72 h). The percentage of apoptotic
      cells were measured by flow cytometry. Real-time quantitative RT-PCR was
      performed to estimate the mRNA expression of P300 in MCF-7 and MRC-5 with CTB at
      different times. ELISA and Bradford protein techniques were used to detect levels
      of total and acetylated P53 protein generated in MCF-7 and MRC-5. RESULTS: Our
      findings indicated that CTB could effectively induce apoptosis in MCF-7
      significantly higher than MRC-5. We showed that expression of P300 was up
      regulated by increasing time of CTB treatment in MCF-7 but not in MRC-5 and the
      acetylated and total P53 protein levels were increased more in MCF-7 cells than
      MRC-5. CONCLUSION: CTB could induce acetylation of P53 protein through increasing
      expression of P300 and consequently induce the significant cell death in MCF-7
      but it could be well tolerated in MRC-5. Therefore, CTB could be used as an anti
      cancer agent.

PMID- 23977653
TI  - The effect of aqueous cinnamon extract on the apoptotic process in acute myeloid
      leukemia HL-60 cells.
AB  - BACKGROUND: Acute promyelocytic leukemia (APL) is an acute leukemia diagnosed by
      translocation of chromosomes 15 and 17 [T (15,17)] and aggregation of neoplastic
      promyelocytes which are incapable of being converted into mature cells. Today,
      many tend to use medicinal herbs in studies and clinical applications for
      treatment of cancers. Cinnamon with scientific name "cinnamomumzelanicum" is a
      shrub of Laurales order, lauraceae family with cinnamomum genus. It is a
      medicinal shrub with anti-proliferation effect on tumor cells. This study was
      conducted to determine the effects of aqueous cinnamon extract on HL-60 cells as
      a model for APL. MATERIALS AND METHODS: In this in vitro experimental study, HL
      60 cell line was cultured under the influence of cinnamon extract's
      concentrations of 0.01, 0.1, 1, and 2 mg/ml in with intervals of 24, 48, and 72
      h. Growth inhibition and toxic effects of cinnamon extract were evaluated through
      tetrazolium salt reduction. The effect of this herb on the cell cycle was studied
      by flow cytometry. The Hoechst stain was used to detect apoptotic cell nuclei.
      RESULTS: Cinnamon extract inhibited the growth of HL-60 cells as correlated with
      concentration and time. After 72 h of treating HL-60 cells with 0.01 mg/l
      cinnamon extract, the growth of cells was inhibited by 90.1%. Cinnamon extract
      stopped the cell cycle in G1 phase and the Hoechst staining verified the
      apoptotic process in those cells. CONCLUSION: Considering the inhibitory property
      of cinnamon extract, we recommend it as a single drug or besides other
      medications for treating promyelocytic leukemia.

PMID- 23977654
TI  - Minimal gene selection for classification and diagnosis prediction based on gene
      expression profile.
AB  - BACKGROUND: Up to date different methods have been used in order to dimensions
      reduction, classification, clustering and prediction of cancers based on gene
      expression profiling. The aim of this study is extracting most significant genes
      and classifying of Diffuse Large B-cell Lymphoma (DLBCL) patients on the basis of
      their gene expression profiles. MATERIALS AND METHODS: We studied 40 DLBCL
      patients and 4026 genes. We utilized Artificial Neural Network (ANN) for
      classification of patients in two groups: Germinal center and Activated like. As
      we were faced with low number of patients (40) and numerous genes (4026), we
      tried to deploy one optimum network and achieve to minimum error. Moreover we
      used signal to noise (S/N) ratio as a main tool for dimension reduction. We tried
      to select suitable training data and so to train just one network instead of 26
      networks. Finally, we extracted two most significant genes. RESULT: In this study
      two most significant genes based on their S/N ratios were selected. After
      selection of suitable training samples, the training and testing error were 0 and
      7% respectively. CONCLUSION: We have shown that the use of two most significant
      genes based on their S/N ratios and selection of suitable training samples can
      lead to classify DLBCL patients with a rather good result. Actually with the aid
      of mentioned methods we could compensate lack of enough number of patients,
      improve accuracy of classifying and reduce complication of computations and so
      running time.

PMID- 23977655
TI  - Delayed cerebellar ataxia: A rare self limiting complication of plasmodium
      falciparum malaria.
AB  - The classic presentation of malaria with paroxysms of fever is seen only in 50
      70% of the patients. The development of immunity, the increasing resistance to
      anti-malarial drugs, and the indiscriminate use of anti-malarial drugs have led
      to malaria with the presentation of unusual features. Cerebellar ataxia,
      extrapyramidal rigidity and various psychiatric symptoms have been described
      either as early manifestations of cerebral malaria or as a part of post malaria
      neurological syndrome. In this case report, we will discuss one such patient of
      falciparum malaria infection who developed midline cerebellar signs, and
      responded to anti-malarial treatment. 

PMID- 23977656
TI  - Colloid milium.
AB  - Colloid milium is a rare cutaneous condition with at least three distinct
      subtypes, characterized clinically by the development of yellowish translucent
      papules or plaques on sun-exposed skin, and histologically by the presence of
      colloid in the dermal papillae. In this case report, we present a man with
      multiple small papules on dorsum of his hands that in pathology confirmed to be
      colloid milium. Colloid milium is more commonly observed in fair-skin patients
      and remain unchanged; however our patient had dark skin type (Fitzpatrick skin
      type III) and lesions were increasing in summer and decreasing in winter. 

PMID- 23977657
TI  - Tuberculous dactylitis (spina ventosa) with concomitant ipsilateral axillary
      scrofuloderma in an immunocompetent child: A rare presentation of skeletal
      tuberculosis.
AB  - Tuberculous dactylitis is a distinctly uncommon, yet well recognized form of
      tuberculosis involving the small bones of the hand or foot. It occurs in young
      children in endemic areas under 5 years of age. Tuberculosis of the short tubular
      bones like phalanges, metacarpals or metatarsals is quite uncommon beyond 6 years
      of age, once the epiphyseal centers are well established. The radiographic
      features of cystic expansion have led to the name "Spina Ventosa" for tuberculous
      dactylitis of the short bones. Scrofuloderma is a mycobacterial infection
      affecting children and young adults, representing direct extension of
      tuberculosis into the skin from underlying structures e.g. lymph nodes. An 8-year
      old malnourished girl had multiple axillary ulcers with lymphadenopathy.
      Tuberculous dactylitis with ipsilateral axillary scrofuloderma was suspected on
      clinical and radiological grounds. The suspicion was confirmed by histology and
      bacteriology. The patient responded to antitubercular drugs with progressive
      healing of the lesions without surgery. Concomitant presence of these dual
      lesions suggesting active disseminated tuberculosis in immune-competent child
      over 6 years is very rare and hardly reported. 

PMID- 23977658
TI  - The demographics and outcome of patients with penetrating abdominal trauma
      admitted to emergency medicine department: A descriptive cross-sectional study.
AB  - BACKGROUND: This study was performed to determine the demographic and outcome of
      penetrating abdominal trauma in patients attending to emergency medicine
      department. MATERIALS AND METHODS: This was a descriptive cross-sectional study
      in Imam Hossein Medical Center. Seventy five patients who came to our department
      with penetrating abdominal trauma during a 1 year period were enroled into this
      study and their demographic data and outcome (during the hospitalization) were
      recorded. The study was at Imam Hossein Medical Center, Tehran, Iran, from 2009
      to 2010. RESULTS: OUR FINDINGS INDICATE THESE NOTABLE RESULTS: 84% of patients
      were less than 40 years old, most patients attended emergency department during
      the spring and summer, 72 patients (96%) arrived between 7 pm and 7 am, 74
      patients (98.7%) had stab wound and one person (1.3%) was shot, eventually 46
      patients (61%) had laparatomy performed and 2 patients (2.7%) died. 59 patients
      out of 75 study cases appealed to police department and legal medicine council.
      CONCLUSIONS: The incidence of abdominal penetrating trauma due to stab wound is
      much higher than gunshot in our community, which indicates the importance of
      educating the emergency staff and preparing the emergency department work place
      to attend to these patients, especially during the night hours.

PMID- 23977659
TI  - CCR3, CCR4, CCR5, and CXCR3 expression in peripheral blood CD4+ lymphocytes in
      gastric cancer patients.
AB  - BACKGROUND: CD4+(TH1, and TH2) cell groups in the point of view of chemokine
      receptor expression were considered in blood of stomach cancer patients.
      MATERIALS AND METHODS: The percentage of blood CD4+ T cells expressing chemokine
      receptors (before and after gastrectomy) was determined by flow cytometry (Becton
      Dickinson, USA) using the following chemokine receptor antibodies: anti-CCR5,
      anti-CXCR3, anti-CCR3 and anti-CCR4. RESULTS: The means of CD4(+) CCR5(+)
      expressing cells was 1.23% +/- 0.90, 0.83% +/- 0.34 and 1.34% +/- 0.74 in
      control, pre- and post-operation groups, respectively. CD4(+) CXCR3(+) expressing
      cells were 19.09% +/- 8.4, 16.95% +/- 5.71 and 25.08% +/- 9.31, respectively.
      Similar pattern was seen for CD4(+) CCR3(+) and CD4(+) CCR4(+) expressing cells.
      Pearson correlation analysis shows no relationship between CCR3 and CCR4
      expressions on TCD4 cells (r = 0.211, P = 0.126). The complex expression TH1
      (CD4(+) CXCR3(+) CCR5(+)) receptors determined 1.14% +/- 0.54 for control group,
      0.86% +/- 0.49 for pre-T and 1.57% +/- 0.67 for post-T group. Moreover, the TH2
      (CD4(+) CCR3(+) CCR4(+)) expression was 1.60% +/- 1.05 for control group, 1.57%
      +/- 0.83 for pre-T and 1.27% +/- 0.66 for post-treatment group. Pearson
      correlation analysis shows that only the CCR3 and CCR5 expression was
      statistically correlated (r = 0.321, P = 0.018). CONCLUSION: Due to low
      expression of CCR5 in TH1 and CCR3 in TH2 cells, it seems that utility of these
      is extremely limited for clinical evaluation, but not scientific purpose.
      Moreover, considering the CXCR3 for TH1 cells and CCR4 expression for TH2 cells,
      due to considerable expression, may be practical.

PMID- 23977660
TI  - Modification of diet in renal disease and Cockraft-Gaultformula accuracy in
      glomerular filtration rate estimation in Iranian adults.
AB  - INTRODUCTION: The aim of this study was to evaluate the accuracy of modification
      of diet in renal disease (MDRD) and Cockraft-Gault (C-G) formulas for estimating
      GFR in a sample of Iranian adult. MATERIALS AND METHODS: This study was an
      analytic cross-sectional study on 54 patients with chronic kidney disease.
      Glomerular filtration rate was measured by kidney scan via TC99m-labeled
      diethylenetriaminepentaacetic acid, and it was estimated by MDRD and Cockraft
      Gault formulas. RESULTS: The mean of measured GFR and estimated GFR by MDRD and C
      G formulas was 61.64 +/- 34.26 ml/min, 51.80 +/- 25.47, and 54.29 +/- 24 ml/min
      respectively (P-value < 0.001, r = 0.818 and P-value < 0.001, r = 0.847,
      respectively). Pearson correlation test showed direct linear relationship between
      sGFR and GFR as estimated by the Cockraft-Gault and MDRD formulas. CONCLUSION:
      Based on our results, modification of diet in renal disease (MDRD) and Cockraf
      Gault (C-G) formulas are accurate formulas in Iranian adults but they need a
      correction factor.

PMID- 23977661
TI  - WT1 protein expression in astrocytic tumors and its relationship with cellular
      proliferation index.
AB  - BACKGROUND: Although Wilms' tumor gene (WT1) was initially known as a tumor
      marker in Wilms' tumor, nowadays its role is well known in other sorts of
      malignancy. This study aimed to evaluate WT1 protein expression levels and its
      association with cellular proliferation in astrocytic brain tumors by
      immunohistochemical methods. MATERIALS AND METHODS: This cross-sectional study
      performed on 73 randomly selected archived tissue samples of astrocytic brain
      tumors. Sections were observed after immunohistochemical staining regarding WT1
      protein expression and MIB-1 staining index. Tumors were classified based on
      World Health Organization grading system. RESULTS: WT1 protein expression was
      seen in the majority of samples (97.3%) with significantly higher index in high
      grade tumors (P<0.001). MIB-1 staining index was also significantly higher in
      high-grade tumors (P<0.001). Moreover, a significantly positive correlation was
      found between WT1 protein expression and MIB-1 staining index (r: 0.64, P<0.001).
      CONCLUSION: Astrocytic brain tumors express WT1 protein. It was also found that
      high-grade tumors are accompanied with higher WT1 protein expression, which is
      correlated with MIB-1 staining index. WT1 can be used as a marker of malignant
      cell proliferation and diagnostic tool to differentiate normal astrocytes from
      neoplastic cells.

PMID- 23977662
TI  - Case report of the extramedullary hematopoiesis presented as a hypervascular
      intracranial mass.
AB  - Thalassemia is a hematologic disorder that causes ineffective hematopoiesis and
      is related to severe anemia, iron overload, extramedullary hematopoiesis, and
      hepatomegaly. Hepatomegaly is related to significant extramedullary
      hematopoiesis. The other sites that are involved in extramedullary hematopoiesis
      are spleen, lymph nodes, paraspinal regions, kidney, pleura, and intestine, but
      intracranial involvement is a rare presentation. We discuss about a case with
      intracranial medullary hematopoiesis in a thalassemic patient. 

PMID- 23977663
TI  - Cancer problem in Peutz-Jeghers syndrome.
AB  - Peutz-Jeghers syndrome is a rare autosomal dominantly inherited condition,
      characterized by the presence of hamartomatous gastrointestinal polyps and
      mucocutaneous pigmentation. Patients with this syndrome can be associated with
      other neoplasms such as ovarian neoplasms known as sex-cord tumor with annular
      tubules that are associated in one third of the cases with this syndrome and
      other types of malignancies. We report a 42-year-old woman with a history of
      Peutz-Jeghers Syndrome and bilateral breast cancer that presented with abnormal
      uterine bleeding. Total abdominal hysterectomy with bilateral salpino
      oophorectomy was done and an ovarian sex cord tumor with annular tubules was
      incidentally diagnosed. By reviewing literatures and in agreement with previous
      studies we suggest routine screening for malignancies in patients with Peutz
      Jeghers syndrome. 

PMID- 23977664
TI  - Bupivacaine liposome injectable suspension: a new approach to postsurgical pain.
AB  - A multivesicular liposomal formulation of bupivacaine which can provide prolonged
      postsurgical pain relief has been developed. Two pivotal placebo-controlled phase
      III trials, one in hemorrhoidectomy and one in bunionectomy procedures, showed
      that wound infiltration of the suspension at the end of surgery could provide
      analgesia for up to 72 hours, reduce the amount of opiate rescue medications, the
      time to their first use and increase patient satisfaction. Liposomal bupivacaine
      was generally well tolerated, with no signal of QTc prolongation or evidence of
      impaired wound healing. A small open U.S. health economic study showed benefits
      (versus patient-controlled analgesia) for the preparation in decreasing total
      opioid use, length of hospital stay and total hospital costs. Further larger
      studies are warranted, in particular using bupivacaine hydrochloride as the
      comparator. 

PMID- 23977665
TI  - Radium Ra 223 dichloride in castration-resistant prostate cancer.
AB  - Radium Ra 223 dichloride (Xofigo(r), formerly Alpharadin) is one of the
      representative alpha-particle-emitting isotopes that delivers radiation with a
      higher biological effect to a more localized area. Preclinical studies in mouse,
      rat and canine models have demonstrated that radium Ra 223 dichloride has a
      definite skeletal affinity and antitumor effect with a relatively low toxicity on
      bone marrow. More recently, in a large randomized phase III trial (ALSYMPCA),
      patients with bone metastasis and castration-resistant prostate cancer (CRPC)
      received six cycles of 50 kBq/kg of radium Ra 223 dichloride in 4-week intervals.
      In these men, radium Ra 223 dichloride improved the median overall survival by
      3.6 months when compared to the placebo group. Collectively, these results
      suggest that radium Ra 223 dichloride is a promising candidate for managing bone
      metastases in patients with CRPC. 

PMID- 23977667
TI  - Pharmacological strategies for preventing type 2 diabetes in patients with
      impaired glucose tolerance.
AB  - Type 2 diabetes is an increasingly prevalent disease in the United States, and is
      associated with microvascular and macrovascular complications. Prediabetes, which
      is defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance
      (IGT), increases the risk of development of type 2 diabetes. Lifestyle
      improvements, including weight loss and increased physical activity are effective
      in reducing the conversion of IGT to type 2 diabetes by 58%. However, lifestyle
      interventions alone may be difficult to maintain. Oral pharmacological agents
      used to treat type 2 diabetes that improve insulin sensitivity, preserve beta
      cell function and delay carbohydrate metabolism have been shown to prevent the
      progression of IGT to type 2 diabetes. The risk reduction of diabetes using
      metformin, pioglitazone, acarbose, valsartan and orlistat in clinical studies has
      ranged from 14 to 72%. Therefore, persons with IGT tolerance may benefit from
      pharmacological therapy to prevent the development of type 2 diabetes. 

PMID- 23977666
TI  - Trametinib for the treatment of melanoma.
AB  - Advanced melanoma traditionally has had poor prognosis with limited, modestly
      effective and relatively toxic systemic treatment options like cytotoxic
      chemotherapy (dacarbazine) and immunomodulating agents (high-dose interleukin-2
      and ipilimumab) which have response rates of 6-20%. With the identification of
      BRAF mutations found to be present in 50% of melanomas and the clinical success
      of serine/threonine-protein kinase B-raf inhibitors the prognostic landscape of
      melanoma has changed considerably. Vemurafenib and dabrafenib have been at the
      forefront of antimelanoma-targeted agents with a tolerable side effect profile
      and efficacy that compared well with the standard chemotherapy. These
      characteristics have led to the regulatory approval of both agents for the
      treatment of melanoma. However, these agents are not curative and have a short
      life span primarily due to rapidly occurring drug resistance. More recently,
      mitogen-activated protein kinase kinase (MEK) inhibitors have been found to have
      strong anticancer activity independently as well as when combined with other
      agents like B-raf inhibitors due to their activity downstream of RAF. Preclinical
      data and limited clinical data suggest that MEK inhibitors may be a component of
      effective therapy for a broad spectrum of cancers with other oncogenic drivers. 

PMID- 23977668
TI  - A report from the 7th International AIDS Society Conference on HIV Pathogenesis,
      Treatment and Prevention (June 30-July 3, 2013 - Kuala Lumpur, Malaysia).
AB  - Effective antiretroviral drugs have been developed that, if continuously
      administered (although with simplification strategies once a patient's viral
      titer is suppressed) allow for a functional cure resulting in an almost normal
      life despite the presence of viral reservoirs. In that sense, observations that
      combination antiretroviral therapy has an untoward suppressive effect on antibody
      dependent cellular cytotoxicity against T cells permitting the establishment of
      such viral reservoirs were discussed for its implications in the use of vaccines
      and/or modulators of the immune function to clear latent infections and the risk
      for reactivation (Madhavi, V. et al., Abst MOLBPE05). In addition to latent viral
      reservoirs, individual patient characteristics may also influence response to
      antiretroviral therapy, as exemplified by the increased likelihood of highly
      active antiretroviral therapy in patients carrying certain polymorphic variants
      (rs2229109, rs6961419) of the P-glycoprotein 1 gene (Dias, J. et al., Abst
      MOPE034). These, and many other important news derived from research into novel
      approaches to fight HIV infection were discussed during the International AIDS
      Society (IAS) meeting in Kuala Lumpur, as summarized in the following report. 

PMID- 23977669
TI  - Single-molecule observation of the K(+)-induced switching of valinomycin within a
      template network.
AB  - The K(+)-induced switching of valinomycin has been studied using a molecular
      template formed by an aromatic oligoamide macrocycle at the liquid/solid
      interface by scanning tunneling microscopy (STM). Individual valinomycin and its
      K(+) complex can be identified and resolved in the molecular template, and the
      high-resolution STM images of valinomycin and its K(+) complex show triangle-like
      and cyclic structural characteristics, respectively. 

PMID- 23977670
TI  - Nonvolatile functional molecular liquids.
AB  - The realisation of technologically high potential molecular materials as an
      innovative replacement for currently used materials requires sensible molecular
      design and subtle implementation. One such research concept "liquid chemistry"
      has recently been introduced as a third-generation of liquid materials after the
      first and second generations of solvent liquids and ionic liquids, respectively.
      The outstanding features of novel organic molecular liquid matter are solvent
      free neat phase at room-temperature, nonvolatile, tunable optic and/or electronic
      functions, processability, etc. The availability of a paintable/printable liquid
      phase which can accommodate various dopants to generate functional composites is
      the main attraction of these molecular liquids. As promising candidates, emitting
      and semiconducting liquid materials have already been practically demonstrated
      and which may replace inorganic or self-assembled organic semiconductors in
      performance and processability. Compared to ionic liquid materials obtained by
      lowering the glass transition temperature through ionic interactions, covalently
      functionalised organic liquid matter is conceptually unique and exhibits several
      advantages. In this feature article, the recent developments in the emerging
      research field of functional molecular liquid materials are discussed. 

PMID- 23977671
TI  - Zn2+/Cd2+ optical discrimination by fluorescent chemosensors based on 8
      hydroxyquinoline derivatives and sulfur-containing macrocyclic units.
AB  - Four new fluorescent chemosensors for metal ions based on 8-hydroxyquinoline (8
      HDQ) derivatives and sulfur-containing macrocyclic units were synthesized and
      characterized, namely 1-(5-chloro-8-hydroxy-7-quinolinylmethyl)-1-aza-4,7,10
      trithiacyclododecane (L1), 1-(5-chloro-8-hydroxy-7-quinolinylmethyl)-1-aza-4,13
      dithia-7,10-dioxacyclopentadecane (L2), 1-(8-hydroxy-2-quinolinylmethyl)-1-aza
      4,7,10-trithiacyclododecane (L3), and 1-(8-hydroxy-2-quinolinylmethyl)-1-aza-4,13
      dithia-7,10-dioxacyclopentadecane (L4). Preliminary fluorimetric titrations
      indicated L1 as the only member of the family of ligands to give a selective CHEF
      type response to the presence of Zn(2+) in MeCN-H2O (1:1, v/v) solutions, which
      allowed imaging of this metal ion in Cos-7 cells in vitro. The other ligands
      either did not show any fluorescence response (L3, L4) to any of the metal ions
      considered (Cu(2+), Zn(2+), Cd(2+), Hg(2+) and Pb(2+)) or gave (L2) a CHEF-type
      response also to the presence of Cd(2+). The coordination properties of L1
      towards Zn(2+) were, therefore, fully investigated by potentiometric measurements
      and absorption and emission spectroscopy at different pH values, which indicated
      that the formation of 2:1 L1/Zn(2+) complexes is responsible for the CHEF-type
      effect observed. The complexes [Zn(L1)2H2O](BF4)2 and [Zn(L3)](ClO4)2 were
      characterized in the solid state by X-ray crystallography, and DFT calculations
      were performed to understand the origin of the Zn(2+)/Cd(2+) optical
      discrimination of the 8-HDQ-based "conjugate" fluorescent chemosensors reported.

PMID- 23977672
TI  - The pros and cons of probiotics.
AB  - Research into the human microbiome has encouraged proliferation of probiotic
      foods and supplements. Although the health claims seem legit, Carrie Arnold finds
      not everyone is convinced.

PMID- 23977673
TI  - Alarm bells over MERS coronavirus.
AB  - Middle East coronavirus is causing alarm among researchers and international
      health officials. Neil Bennet looks at the unfolding situation.

PMID- 23977674
TI  - HIV-1 capsid structure nailed.

PMID- 23977675
TI  - Authors' response.

PMID- 23977676
TI  - Authors' response.

PMID- 23977677
TI  - Authors' response.

PMID- 23977678
TI  - Research impact: Altmetrics make their mark.

PMID- 23977679
TI  - Mutation scanning analysis of genetic variation within and among Echinococcus
      species: implications and future prospects.
AB  - Adult tapeworms of the genus Echinococcus (family Taeniidae) occur in the small
      intestines of carnivorous definitive hosts and are transmitted to particular
      intermediate mammalian hosts, in which they develop as fluid-filled larvae
      (cysts) in internal organs (usually lung and liver), causing the disease
      echinococcosis. Echinococcus species are of major medical importance and also
      cause losses to the meat and livestock industries, mainly due to the condemnation
      of infected offal. Decisions regarding the treatment and control of
      echinococcosis rely on the accurate identification of species and population
      variants (strains). Conventional, phenetic methods for specific identification
      have some significant limitations. Despite advances in the development of
      molecular tools, there has been limited application of mutation scanning methods
      to species of Echinococcus. Here, we briefly review key genetic markers used for
      the identification of Echinococcus species and techniques for the analysis of
      genetic variation within and among populations, and the diagnosis of
      echinococcosis. We also discuss the benefits of utilizing mutation scanning
      approaches to elucidate the population genetics and epidemiology of Echinococcus
      species. These benefits are likely to become more evident following the complete
      characterization of the genomes of E. granulosus and E. multilocularis.

PMID- 23977680
TI  - A nonradioactive electrophoretic mobility shift assay for measurement of pregnane
      X receptor binding activity to CYP3A4 response element.
AB  - The electrophoretic mobility shift assay (EMSA) is a method for the study of
      specific DNA-protein interactions in vitro. The pregnane X receptor (PRX) is a
      key xenobiotic sensor that regulates the expression of drug-metabolizing enzymes
      andmany other genes. Radiolabeled 32P-DNA-probes had been used in studies of PXR
      DNA interactions. There is an increasing need for nonradioactive assays, due to
      the health, safety and environmental issues. In the current study, we present a
      protocol for the nonradioactive electrophoretic mobility shift assay, allowing
      studying interactions between human PXR with promoter DNA sequences.

PMID- 23977681
TI  - Graphene oxide and reduced graphene oxide as novel stationary phases via
      electrostatic assembly for open-tubular capillary electrochromatography.
AB  - We present here the application of graphene oxide (GO) and reduced graphene oxide
      (GOOH) sheet as novel stationary phases for open-tubular CEC (OTCEC) separation
      based on electrostatic assembly. The inner walls of a bare capillary column was
      first modified by ionic assembly of poly (diallyldimethylammonium chloride)
      (PDDA), and then negatively charged GO or GOOH was easily assembled on a
      positively charged interior walls of the capillary by electrostatic force.
      Scanning Electron Microscope images showed that GO and GOOH can still maintain
      sheet-layer-like structure when coated onto the capillary via electrostatic
      assembly. The chromatographic properties of the GO and GOOH coated columns were
      evaluated via OTCEC separations of various kinds of analytes, including three
      acid nitrophenol isomers, three basic nitroaniline isomers, and four neutral
      PAHs. Efficient separations of all the analytes were achieved with optimized
      buffer pH and organic additive. The reproducibility and stability of the GO or
      GOOH coated columns were investigated. Our results indicate the capability of
      application GO or GOOH sheet in OTCEC separation, which can be coated on the
      inner wall of fused-silica capillary via electrostatic assembly.

PMID- 23977682
TI  - Improved sulfoalkylbetaine-based organic-silica hybrid monolith for high
      efficient hydrophilic interaction liquid chromatography of polar compounds.
AB  - A novel sulfoalkylbetaine-based zwitterionic organic-silica hybrid monolith was
      synthesized by using 3-dimethyl-(3-(N-methacrylamido) propyl) ammonium propane
      sulfonate (DMMPPS, neutral sulfoalkyl-betaine monomer). The added amount of
      zwitterionic monomer was significantly increased when DMMPPS was used instead of
      the conventionally used acidic sulfoalkyl-betaine monomer, that is, the N,N
      dimethyl-N-methacryloxyethyl-N-(3-sulfopropyl) ammonium betaine, and this led to
      a significantly improved hydrophilicity of the monolith. The DMMPPS-based organic
      silica hybridmonolith exhibited good mechanical stability and excellent
      separation performance. About ~20 mMU plate height (corresponding to column
      efficiency of ~50,000 plates/m) was obtained for nucleoside at the linear
      velocity of 1 mm/s. The proposed monolithic column was successfully applied to
      separate purines/pyrimidines, nucleotides, and tryptic digest of bovine
      hemoglobin in a nano-HILIC mode, and the results demonstrated that such monolith
      has the potential for separation of a variety of hydrophilic substances.

PMID- 23977683
TI  - Dual-micropillar-based microfluidic platform for single embryonic stem cell
      derived neuronal differentiation.
AB  - We developed the dual-micropillar-based microfluidic platform to direct embryonic
      stem (ES) cell fate. 4 * 4 dual-micropillar-based microfluidic platform consisted
      of 16 circular-shaped outer micropillars and 8 saddle-shaped inner micropillars
      in which single ES cells were cultured. We hypothesized that dual-micropillar
      arrays would play an important role in controlling the shear stress and cell
      docking. Circular-shaped outer micropillars minimized the shear stress, whereas
      saddle-shaped innermicropillars allowed for docking of individual ES cells. We
      observed the effect of saddle-shaped inner micropillars on cell docking in
      response to hydrodynamic resistance. We also demonstrated that ES cells cultured
      for 6 days within the dual-micropillar-based microfluidic platform differentiated
      into neural-like cells. Therefore, this dual-micropillar-based microfluidic
      platform could be a potentially powerful method for screening of lineage
      commitments of single ES cells.

PMID- 23977684
TI  - Staining of proteins for 2D SDS-PAGE using Coomassie Blue--speed versus
      sensitivity?
AB  - Several new fast staining protocols for the visualization of proteins separated
      by SDS-PAGE utilizing Coomassie Blue staining (CBS) have been described in
      literature. The sensitivity of a newly designed staining protocol is usually
      estimated using 1D SDS-PAGE of serially diluted protein samples. However, this
      approach is not predictive and satisfactory for 2D SDS-PAGE capable of resolving
      hundreds or thousands of different proteins in a single analysis. In this work, a
      new fast staining protocol recently introduced by Dong et al. (PLoS One 2011, 6,
      e22394) was compared to colloidal CBS. The number of detectable spots in 2D SDS
      PAGE of identical blood plasma samples in repeated runs was chosen as a
      sensitivity criterion. Further, the influence of gel boiling on the subsequent
      protein identification by MS was investigated. In spite of its advantages, the
      staining protocol according to Dong et al. (PLoS One 2011, 6, e22394) seems to be
      less sensitive than colloidal Coomassie staining when the number of detected
      spots is the evaluating criterion. No obvious influence of gel boiling on the
      protein identification was observed.

PMID- 23977685
TI  - Subject to question.

PMID- 23977686
TI  - Male pubertal development: are endocrine-disrupting compounds shifting the norms?
AB  - Endocrine-disrupting compounds (EDCs) are synthetic or natural compounds that
      interfere with endogenous endocrine action. The frequent use of chemicals with
      endocrine active properties in household products and contamination of soil,
      water, and food sources by persistent chemical pollutants result in ubiquitous
      exposures. Wildlife observations and animal toxicological studies reveal adverse
      effects of EDCs on reproductive health.In humans, a growing number of
      epidemiological studies report an association with altered pubertal timing and
      progression. While these data are primarily reported in females,this review will
      focus on the small number of studies performed in males that report an
      association of polychlorinated biphenyls with earlier sexual maturity rating and
      confirm subtle effects of lead, dioxins, and endosulfan on delaying pubertal
      onset and progression in boys. Recent studies have also demonstrated that EDC
      exposure may affect pubertal testosterone production without having a noticeable
      effect on sexual maturity rating.A limitation to understand the effects of EDCs
      in humans is the potential for confounding due to the long temporal lag from
      early-life exposures to adult outcomes. The complex interplay of multiple
      environmental exposures over time also complicates the interpretation of human
      studies. These studies have identified critical windows of vulnerability during
      development when exposures to EDCs alter critical pathways and affect postnatal
      reproductive health. Contemporaneous exposures can also disrupt the hypothalamic
      pituitary-gonadal axis. This paper will review the normal process of puberty in
      males and summarize human data that suggest potential perturbations in pubertal
      onset and tempo with early-life exposures to EDCs.

PMID- 23977687
TI  - Response.

PMID- 23977688
TI  - Response.

PMID- 23977689
TI  - Response.

PMID- 23977690
TI  - Response.

PMID- 23977691
TI  - Response.

PMID- 23977692
TI  - Response.

PMID- 23977693
TI  - Response.

PMID- 23977694
TI  - Response.

PMID- 23977695
TI  - Reply: To PMID 23157182.

PMID- 23977696
TI  - Author response.

PMID- 23977698
TI  - New anti-inflammatory targets for chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is associated with chronic
      inflammation of the peripheral airways and lung parenchyma, which leads to
      progressive obstruction of the airways. Current management with long-acting
      bronchodilators does not reduce disease progression, and there are no treatments
      that effectively suppress chronic inflammation in COPD. An increased
      understanding of the inflammatory processes that are involved in the
      pathophysiology of COPD has identified several new therapeutic targets. This
      Review discusses some of the most promising of these targets, including new
      antioxidants, kinase inhibitors and drugs that target cellular senescence,
      microbial colonization, epigenetic regulation of inflammatory gene expression and
      corticosteroid resistance.

PMID- 23977699
TI  - Applications of gold nanoparticles in the detection and identification of
      infectious diseases and biothreats.
AB  - The situation of infectious diseases and biothreats all over the world remains
      serious. The effective identification of such diseases plays a very important
      role. In recent years, gold nanoparticles have been widely used in biosensor
      design to improve the performance for the detection of infectious diseases and
      biothreats. Here, recent advances of gold-nanoparticle-based biosensors in this
      field are summarized.

PMID- 23977700
TI  - Take my job--please!

PMID- 23977701
TI  - 8 things you can do to prevent a stroke.  Regardless of your age or family
      history, a stroke doesn't have to be inevitable.  Here are some ways to protect
      yourself starting today.

PMID- 23977702
TI  - Radiation for breast cancer linked to heart problems.

PMID- 23977703
TI  - Ask the doctor. At 65, I have begun to notice tiny threadlike shapes in my
      vision, which my doctor calls "floaters." Should I be concerned?

PMID- 23977697
TI  - Small-molecule modulation of neurotrophin receptors: a strategy for the treatment
      of neurological disease.
AB  - Neurotrophins and their receptors modulate multiple signalling pathways to
      regulate neuronal survival and to maintain axonal and dendritic networks and
      synaptic plasticity. Neurotrophins have potential for the treatment of
      neurological diseases. However, their therapeutic application has been limited
      owing to their poor plasma stability, restricted nervous system penetration and,
      importantly, the pleiotropic actions that derive from their concomitant binding
      to multiple receptors. One strategy to overcome these limitations is to target
      individual neurotrophin receptors - such as tropomyosin receptor kinase A (TRKA),
      TRKB, TRKC, the p75 neurotrophin receptor or sortilin - with small-molecule
      ligands. Such small molecules might also modulate various aspects of these
      signalling pathways in ways that are distinct from the programmes triggered by
      native neurotrophins. By departing from conventional neurotrophin signalling,
      these ligands might provide novel therapeutic options for a broad range of
      neurological indications.

PMID- 23977704
TI  - Ask the doctor. An MRI of my knee shows I have a torn medial meniscus and mild
      osteoarthritis. What treatment options should I consider?

PMID- 23977705
TI  - Natural ways to relieve constipation.  A few at-home tips can help you avoid the
      need for harsh laxatives.

PMID- 23977706
TI  - Better sleep--without pills.  Before you reach for sleep aids, try these
      techniques to improve your slumber.

PMID- 23977707
TI  - Getting your doctor to listen. How to avoid having unnecessary tests--and getting
      the wrong diagnosis.

PMID- 23977708
TI  - Could less housework equal weight gain?

PMID- 23977709
TI  - Hands-on treatment helps low back pain.

PMID- 23977710
TI  - Aspirin may lower melanoma risk.

PMID- 23977711
TI  - Puzzles in practice. Parotitis.

PMID- 23977712
TI  - Retraction notice to "Vitamin D levels do not predict cardiovascular events in
      statin-treated patients with stable coronary disease" [Am Heart J 2012;164:387
      393].

PMID- 23977713
TI  - Medicare program; hospital inpatient prospective payment systems for acute care
      hospitals and the long-term care hospital prospective payment system and Fiscal
      Year 2014 rates; quality reporting requirements for specific providers; hospital
      conditions of participation; payment policies related to patient status. Final
      rules.
AB  - We are revising the Medicare hospital inpatient prospective payment systems
      (IPPS) for operating and capital-related costs of acute care hospitals to
      implement changes arising from our continuing experience with these systems. Some
      of the changes implement certain statutory provisions contained in the Patient
      Protection and Affordable Care Act and the Health Care and Education
      Reconciliation Act of 2010 (collectively known as the Affordable Care Act) and
      other legislation. These changes will be applicable to discharges occurring on or
      after October 1, 2013, unless otherwise specified in this final rule. We also are
      updating the rate-of-increase limits for certain hospitals excluded from the IPPS
      that are paid on a reasonable cost basis subject to these limits. The updated
      rate-of-increase limits will be effective for cost reporting periods beginning on
      or after October 1, 2013. We also are updating the payment policies and the
      annual payment rates for the Medicare prospective payment system (PPS) for
      inpatient hospital services provided by long-term care hospitals (LTCHs) and
      implementing certain statutory changes that were applied to the LTCH PPS by the
      Affordable Care Act. Generally, these updates and statutory changes will be
      applicable to discharges occurring on or after October 1, 2013, unless otherwise
      specified in this final rule. In addition, we are making a number of changes
      relating to direct graduate medical education (GME) and indirect medical
      education (IME) payments. We are establishing new requirements or have revised
      requirements for quality reporting by specific providers (acute care hospitals,
      PPS-exempt cancer hospitals, LTCHs, and inpatient psychiatric facilities (IPFs))
      that are participating in Medicare. We are updating policies relating to the
      Hospital Value-Based Purchasing (VBP) Program and the Hospital Readmissions
      Reduction Program. In addition, we are revising the conditions of participation
      (CoPs) for hospitals relating to the administration of vaccines by nursing staff
      as well as the CoPs for critical access hospitals relating to the provision of
      acute care inpatient services. We are finalizing proposals issued in two separate
      proposed rules that included payment policies related to patient status: payment
      of Medicare Part B inpatient services; and admission and medical review criteria
      for payment of hospital inpatient services under Medicare Part A.

PMID- 23977714
TI  - VA Health Professional Scholarship and Visual Impairment and Orientation and
      Mobility Professional Scholarship Programs. Final rule.
AB  - The Department of Veterans Affairs (VA) is amending its VA Health Professional
      Scholarship Program (HPSP) regulations. VA is also establishing regulations for a
      new program, the Visual Impairment and Orientation and Mobility Professional
      Scholarship Program (VIOMPSP). These regulations comply with and implement
      sections 302 and 603 of the Caregivers and Veterans Omnibus Health Services Act
      of 2010 (the 2010 Act). Section 302 of the 2010 Act established the VIOMPSP,
      which authorizes VA to provide financial assistance to certain students seeking a
      degree in visual impairment or orientation or mobility, in order to increase the
      supply of qualified blind rehabilitation specialists for VA and the United
      States. Section 603 of the 2010 Act reauthorized and modified HPSP, a program
      that provides scholarships for education or training in certain health care
      occupations.

PMID- 23977715
TI  - Medicare program; FY 2014 hospice wage index and payment rate update; hospice
      quality reporting requirements; and updates on payment reform. final rule.
AB  - This final rule updates the hospice payment rates and the wage index for fiscal
      year (FY) 2014, and continues the phase out of the wage index budget neutrality
      adjustment factor (BNAF). Including the FY 2014 15 percent BNAF reduction, the
      total 5 year cumulative BNAF reduction in FY 2014 will be 70 percent. The BNAF
      phase-out will continue with successive 15 percent reductions in FY 2015 and FY
      2016. This final rule also clarifies how hospices are to report diagnoses on
      hospice claims, and provides updates to the public on hospice payment reform.
      Additionally, this final rule changes the requirements for the hospice quality
      reporting program by discontinuing currently reported measures and implementing a
      Hospice Item Set with seven National Quality Forum (NFQ) endorsed measures
      beginning July 1, 2014, as proposed. Finally, this final rule will implement the
      hospice Experience of Care Survey on January 1, 2015, as proposed.

PMID- 23977716
TI  - TRICARE; reimbursement of sole community hospitals and adjustment to
      reimbursement of critical access hospitals. Final rule.
AB  - This Final Rule implements for Sole Community Hospitals (SCHs) the statutory
      provision at title 10, United States Code (U.S.C.), section 1079(j)(2) that
      TRICARE payment methods for institutional care be determined, to the extent
      practicable, in accordance with the same reimbursement rules as those that apply
      to payments to providers of services of the same type under Medicare. This Final
      Rule implements a reimbursement methodology similar to that applicable to
      Medicare beneficiaries for inpatient services provided by SCHs. It will be phased
      in over a several-year period. This Final Rule also provides for special
      reimbursement for labor/delivery and nursery services in SCHs and creates a
      possible General Temporary Military Contingency Payment Adjustment (GTMCPA) for
      inpatient services in SCHs and for Critical Access Hospitals (CAHs).

PMID- 23977717
TI  - Changes in spontaneous and LPS-induced ex vivo cytokine production and mRNA
      expression in male and female athletes following prolonged exhaustive exercise.
AB  - PURPOSE: The capacity of whole blood cultures to produce cytokines in response to
      endotoxin (LPS) was studied in athletes before, 30 min after, 3 h after and 24 h
      after a half-marathon run. METHODS: Eight well trained men and 8 well trained
      women (6 of them in the late luteal phase of their cycle) participated. EDTA
      blood was incubated with or without LPS for 1 h, and cytokine concentration and
      gene expression were determined. To quantify LPS-dependent release on a per
      monocyte basis (LDR), the mean values of the difference (delta) between cytokine
      concentration in stimulated and unstimulated cultures, normalized to monocyte
      numbers, were calculated. RESULTS: LDR of TNF-alpha was significantly reduced by
      exercise with identical kinetic in men and women. TNF-alpha mRNA expression was
      slightly down-regulated following exercise (P < 0.05), but significantly so only
      in women. LDR of IL-6 was also reduced, but with a faster kinetic in women than
      in men. Similarly, 30 min post-exercise; LDR and spontaneous release of IL-1ra
      were significantly less in women than men. Concomitantly, IL-Ira mRNA was
      significantly elevated in unstimulated and in stimulated cultures in men only. IL
      10 and IL-10 mRNA were significantly induced 30 min following exercise in absence
      of any detectable LDR. Women showed significantly lower levels than men. LDR and
      spontaneous release of IL-8 was enhanced in men and TGF-beta1 in women. A
      significant up-regulation was seen in unstimulated IL-8 mRNA for women and LPS
      stimulated IL-8 mRNA expression for men following exercise. CONCLUSION:
      Altogether, LPS-dependent ex vivo cytokine release was strongly influenced by
      exercise and these changes could only in part be attributed to changes in
      messenger RNA. Results for IL-1ra, IL-6 and IL-10 pointed to a less pronounced
      anti-inflammatory response in women as compared with men. Our results also
      indicate an early production of IL-10 by peripheral blood cells in response to
      exercise.

PMID- 23977718
TI  - Urinary excretion of cytokines versus their plasma levels after endurance
      exercise.
AB  - It has been consistently shown that circulating levels of interleukin (IL)-6, IL
      8, IL-1 receptor antagonist (IL-1ra) and IL-10 increase remarkably following
      endurance exercise longer than 2 h such as marathon and triathlon races. However,
      no studies have compared changes in the plasma and urinary levels of these
      cytokines after endurance exercise, including the recovery period. In the present
      study, we investigated kinetic changes in the urinary excretion of cytokines
      following endurance exercise up to 3 h after exercise to evaluate the magnitude
      of change in comparison to the plasma levels and to explore the possible
      biological significance and the mechanisms of cytokine dynamics following
      exercise. Fourteen male athletes participated in a duathlon race consisting of 5
      km of running, 40 km of cycling, and 5 km of running. Venous blood and urine
      samples were collected before, immediately after, 1.5 h and 3 h after the race.
      Plasma and urine were analyzed using enzyme-linked immunosorbent assays (ELISA).
      Plasma concentrations of lL-1beta, IL-1ra, IL-6, IL-8, IL-10 and monocyte
      chemotactic protein (MCP)-1 increased significantly after the race, whereas
      tumour necrosis factor (TNF)-alpha, IL-2, IL-4, IL-12 and interferon (IFN)-gamma
      did not change significantly. Urinary concentrations of lL-1beta, IL-1ra, IL-2,
      IL-4, IL-6, IL-8, IL-10, IL-12, IFN-gamma and MCP-1 increased significantly after
      the race. When the urine concentrations were adjusted by creatinine
      concentration, urine volume and sampling time, the increases of lL-2, IL-4, IL-8,
      IL-10, IFN-gamma and MCP-1 were evident and these were notably present in urine
      of the stressed athletes suffering from renal tubular epithelial damage. The
      present study provides new evidence that the kinetics and magnitude of changes in
      urinary cytokine concentrations differ from plasma cytokine concentrations
      following endurance exercise, especially, in the recovery period several hours
      after exercise, and that the damaged kidney might be responsible at least in part
      for the kinetics of some cytokines. Urinary cytokines may be sensitive biomarkers
      of the impact of exhaustive exercise workload on renal damage and inflammation in
      the recovery period after endurance exercise.

PMID- 23977719
TI  - Cytokine kinetics in nasal mucosa and sera: new insights in understanding upper
      airway disease of marathon runners.
AB  - Recently, many authors have proposed that mechanisms such as inflammation and/or
      allergies could be partly responsible for cases of upper respiratory tract
      illnesses that affect athletes after exhaustive exercise. Here we studied the
      kinetics of cytokines in the serum and nasal mucosa of athletes after a marathon.
      We were able to demonstrate an increase in serum levels of all interleukins
      studied immediately after the marathon in athletes that present or not with upper
      airways symptoms followed by a return to basal levels 72 hours after the race, as
      described in the literature. Interleukin (IL)-10 behaviour differed in the group
      of asymptomatic athletes. Measurement of this cytokine in protein extract of
      nasal mucosal cells showed increase 72 hours after the marathon. Levels of this
      cytokine in sera were increased at rest in athletes that did not present
      symptoms. These fin- dings suggest that the maintenance of a non-inflammatory
      environment in the mucosal airways is an active process that requires
      participation of the systemic and mucosal immune systems. We propose that the
      understanding of the upper airway disease of the athlete involves the study of
      mucosal and systemic immune systems.

PMID- 23977720
TI  - Effects of regular exercise on neutrophil functions, oxidative stress parameters
      and antibody responses against 4-hydroxy-2-nonenal adducts in middle aged humans.
AB  - Regular exercise has recognized health benefits, partly because it reportedly
      lowers the levels of the oxidation products of proteins and DNA at rest, in
      contrast with the effect of acute exercise. However, when we compared oxidative
      response markers in active middle-aged subjects with those in sedentary ones, the
      level of urinary 8-OHdG was higher in active subjects. Because neutrophils are
      the first line of defense against a variety of infectious diseases, we then
      compared the cell density, functions and apoptosis of neutrophils in active
      subjects with those in sedentary ones. The cell density of neutrophils and
      phagocytosis of opsonized zymosan by neutrophils were higher in active subjects,
      being similar with the reported effects of acute exercise. To determine any
      beneficial effects of oxidative stress in active subjects, we then compared the
      levels of antibodies against 4-hydroxy-2-nonenal adducts in active subjects with
      those in sedentary ones, because 4-hydroxy-2-nonenal is one of the most common
      bioactive aldehyde products of oxidative stress, and because the IgM class of
      antibodies against oxidized low-density lipoprotein is associated with
      atheroprotective properties. The level of the IgM but not the IgG class of
      antibodies against 4-hydroxy-2-nonenal adducts was higher in active subjects.
      Overall, this study revealed that our active middle-aged subjects showed both
      oxidative responses and a higher IgM response to reactive carbonyl derivatives,
      possibly providing a basis for a health benefit by exercise in our active
      subjects.

PMID- 23977721
TI  - Eccentric exercise-induced delayed-onset muscle soreness and changes in markers
      of muscle damage and inflammation.
AB  - The purpose of this study was to determine the relationships among delayed-onset
      muscle soreness (DOMS), muscle damage and inflammatory responses to eccentric
      exercise and investigate the underlying mechanisms. Nine healthy males performed
      one-leg calf-raise exercise with their right leg on a force plate. They performed
      10 sets of 40 repetitions of exercise at 0.5 Hz by the load corresponding to the
      half of their body weight, with a rest for 3 min between sets. DOMS was evaluated
      by a visual analogue scale (VAS). Blood and urine samples were collected before
      and 2, 4, 24, 48, 72 and 96 h post-exercise. Blood samples were analyzed for
      leucocyte differential counts and neutrophil functions (migratory activity and
      oxidative burst activity). We also determined a serum marker of muscle damage,
      myoglobin (Mb), and plasma and urinary prostaglandin E2 as an algesic substance.
      As for the inflammatory mediators, plasma and urine were analyzed for cytokines
      (interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-8, IL-10,
      IL-12p40, IL-12p70, tumour necrosis factor-alpha, interferon-gamma, monocyte
      chemotactic protein-1, granulocyte colony-stimulating factor, macrophage colony
      stimulating factor, and granulocyte macrophage colony-stimulating factor),
      leucocyte activation markers (calprotectin and myeloperoxidase), and neutrophil
      chemotactic factor complement 5a. All subjects reported muscle soreness on
      subsequent days and VAS peaked at 72 h after exercise. Serum Mb concentration
      significantly increased (p < 0.05) at 72 h after exercise as compared with the
      pre-exercise values which was correlated with the increases in VAS at 72 h (r =
      0.73, p < 0.05). Circulating neutrophil count and migratory activity increased
      significantly (p < 0.01, and p < 0.05, respectively) at 4 h after exercise,
      whereas there were no significant changes in the other plasma and urinary
      inflammatory mediators. These results suggest that neutrophils can be mobilized
      into the circulation and migrate to the muscle tissue several hours after the
      eccentric exercise. There were also positive correlations between the exercise
      induced increases in neutrophil migratory activity at 4 h and the increases in Mb
      at 48 h (r = 0.67, p < 0.05). These findings suggest that neutrophil mobilization
      and migration after exercise may be involved in the muscle damage and
      inflammatory processes.

PMID- 23977722
TI  - Influence of vitamin D status on respiratory infection incidence and immune
      function during 4 months of winter training in endurance sport athletes.
AB  - The purpose of this study was to examine the influence of vitamin D status on
      mucosal and systemic immunity and the incidence, severity and duration of upper
      respiratory tract illness (URTI) episodes in endurance athletes during a 16-week
      winter training period. Blood was collected from 225 subjects at the start of the
      study and plasma was analysed for total 25-hydroxy vitamin D (25(OH)D) and
      cathelicidin concentration. Blood was also collected at the end of the study and
      analysed for 25(OH)D and antigen-stimulated cytokine production. Unstimulated
      saliva samples were obtained at the start and at 4-week intervals during the
      study period. Saliva samples were analysed for salivary antimicrobial peptides
      and proteins (AMPs). Weekly training and daily illness logs were kept. At the
      start and end of the study 38% and 55%, respectively, of the athlete cohort had
      inadequate (plasma 25(OH)D 30-50 nmol/L) or deficient (plasma 25(OH)D < 30
      nmol/L) vitamin D status. There was a significantly higher proportion of subjects
      who presented with symptoms of URTI in the vitamin D deficient status group
      (initial plasma 25(OH)D < 30 nmol/L) during the study period than in the optimal
      vitamin D group (> 120 nmol/L) and the total number of URTI symptom days and the
      median symptom-severity score in the vitamin D deficient group was signifi-
      cantly higher than in the other groups. The plasma cathelicidin concentration
      positively correlated with the plasma 25(OH)D concentration and the saliva
      secretory immunoglobulin A (SIgA) secretion rate in the optimal vitamin D status
      group was significantly higher than in the other groups. Low vitamin D status was
      associated with lower pro-inflammatory cytokine production by monocytes and
      lymphocytes. Low vitamin D status could be an important determinant of URTI risk
      in endurance athletes and mucosal as well as systemic immunity may be modified
      via vitamin D-dependent mechanisms.

PMID- 23977723
TI  - Butyrylated starch increases colonic butyrate concentration but has limited
      effects on immunity in healthy physically active individuals.
AB  - BACKGROUND: Butyrate delivery to the large bowel may positively modulate
      commensal microbiota and enhance immunity. OBJECTIVE: To determine the effects of
      increasing large bowel butyrate concentration through ingestion of butyrylated
      high amylose maize starch (HAMSB) on faecal biochemistry and microbiota, and
      markers of immunity in healthy active individuals. DESIGN: Male and female
      volunteers were assigned randomly to consume either two doses of 20 g HAMSB (n =
      23; age 37.9 +/- 7.8 y; mean +/- SD) or a low amylose maize starch (LAMS) (n =
      18; age 36.9 = 9.5 y) twice daily for 28 days. Samples were collected on days 0,
      10 and 28 for assessment of faecal bacterial groups, faecal biochemistry, serum
      cytokines and salivary antimicrobial proteins. RESULTS: HAMSB led to relative
      increases in faecal free (45%; 12-86%; mean; 90% confidence interval; P = 0.02),
      bound (950%; 563-1564%; P < 0.01) and total butyrate (260%; 174-373%; P < 0.01)
      and faecal propionate (41%; 12-77%; P = 0.02) from day 0 to day 28 compared to
      LAMS. HAMSB was also associated with a relative 1.6-fold (1.2- to 2.0-fold; P <
      0.01) and 2.5-fold (1.4- to 4.4-fold; P = 0.01) increase in plasma IL-10 and TNF
      alpha but did not alter other indices of immunity. There were relative greater
      increases in faecal P. distasonis (81-fold (28- to 237-fold; P < 0.01) and F.
      prausnitzii (5.1-fold (2.1- to 12-fold; P < 0.01) in the HAMSB group.
      CONCLUSIONS: HAMSB supplementation in healthy active individuals promotes the
      growth of bacteria that may improve bowel health and has only limited effects on
      plasma cytokines.

PMID- 23977724
TI  - Effects of exercise on immune function in patients with cancer: a systematic
      review.
AB  - BACKGROUND: The role of exercise therapy in the rehabilitation of cancer patients
      and survivors is becoming increasingly important as it is thought to modulate
      immunity and inflammation. More knowledge about the effects of exercise on immune
      function in these patients is needed. Our aim is to systematically review changes
      in immune parameters after acute and chronic exercise in cancer patients.
      RESULTS: Of the 3586 retrieved articles, 21 met the inclusion criteria, and were
      included in this systematic review. The systematic search yielded 18 articles in
      adults, and three in children. Six were of low methodological quality, mainly due
      to lack of blinding of the assessor and high drop-out rates. The effect of
      chronic exercise on immune function was examined in 18 studies, while two studies
      evaluated the effects of acute exercise, and one study combined acute and chronic
      exercise. Following exercise, increases were seen in Natural Killer cytotoxic
      activity, as well as lymphocyte proliferation and the number of granulocytes. The
      number of leukocytes, lymphocytes, Natural Killer cells, T lymphocytes, C
      reactive protein, and pro- and anti-inflammatory mediators remained stable.
      LIMITATIONS: Of the 21 included studies, only three were conducted in the
      pediatric population, and many studies have included small and heterogeneous
      samples. Due to the large variety in exercise training protocols and immune
      parameters, no meta-analysis has been performed. CONCLUSIONS: Various immune
      parameters improved after exercise; however, knowledge of the effects of exercise
      on immune function in cancer patients is still limited. Additional research is
      needed to gain insight into the mechanism underlying the effects of exercise on
      immune function in different populations, and to link these immune parameters to
      clinical outcomes.

PMID- 23977725
TI  - Spinal cord injury: known and possible influences on the immune response to
      exercise.
AB  - A spinal cord injury (SCI) can increase the risk of infection by impacting on
      many aspects of immune function; one particularly well-documented observation is
      a reduction in lymphocyte numbers. The vast majority of lymphoid cells express
      adrenergic receptors. Therefore, autonomic function loss and concomitant
      alterations in resting and post-exercise catecholamine concentrations,
      particularly so in individuals with a tetraplegia, may impact directly on immune
      cells and depress immunity. Other factors are further likely to contribute,
      examples including altered muscular, endocrine and cardiovascular function
      following SCI. However, some alterations, such as increases in natural killer
      cell cytotoxicity following exercise in those with a tetraplegia, are unrelated
      to the catecholamine response. Likewise, mucosal immunity in individuals with a
      tetraplegia appears to be similarly influenced by exercise as in the able-bodied
      population. Indeed, rehabilitation therapy and exercise can increase some
      measures of immunity and autonomic function in those with an SCI. It is therefore
      possible that compensatory mechanisms offset disability-related detriments. This
      may be by way of sympathetic reflex activity, receptor hypersensitivity, or
      parasympathetic and neuroendocrine adjustments. Future work needs to explore
      these mechanisms further to clarify the implications of an SCI on the immune
      response to exercise and susceptibility to infection. In this article, we review
      the impacts of an SCI on immune, and specifically, exercise immune function. The
      relevant anatomical and physiological foundations of the immune system are first
      briefly laid out in order to understand the potential impacts of neural and
      neuroendocrine dysfunction on the immune system. With the limited number of human
      studies available, we have then aimed specifically to gather all relevant
      existing literature on exercise immunology in individuals with an SCI in patient,
      recreationally active and athlete populations. We believe that an understanding
      of the impacts of exercise can provide a tool to help maintain or improve health
      in individuals with an SCI. A comprehensive literature search was conducted using
      the search engines PubMed, SPORTDiscus, Web of Science and Zetoc, search period
      June 2012-February 2013. Key words employed included spinal cord injury,
      immunology, exercise, paraplegic, tetraplegic, upper body exercise, interleukin,
      immunoglobulin, sympathetic, and parasympathetic. All articles and articles
      derived from their reference lists were checked for their suitability.

PMID- 23977726
TI  - Open letter to all authorities and institutions involved in managing curricula of
      physical education in Brazil.

PMID- 23977727
TI  - [Rheumatoid arthritis: what to do if methotrexate fails?].

PMID- 23977728
TI  - [Molluscum contagiosum--a common but poorly understood "childhood disease" and
      sexually transmitted illness].
AB  - Molluscum contagiosum is a viral disease of the skin characterized by discrete,
      multiple, flesh-colored papules. It is caused by a highly infectious, enveloped
      deoxyribonucleic acid virus, called molluscum contagiosum virus (MCV). Molluscum
      contagiosum is very common in children, sexually active adults and
      immunocompromised patients, especially those who are infected with the human
      immunodeficiency virus. MCV transmission usually takes place through direct skin
      to-skin contact. Infections in childhood are often linked to swimming-pool
      attendance. Adults are infected usually through sexual contact. An intimate skin
      to-skin contact is sufficient for transmission of the virus. In immunocompetent
      adults, the warts remain in the genital area and adjacent regions of the skin. In
      children and patients with immunocompromised conditions, however, various regions
      of the body are usually affected. Therapy of molluscum contagiosum should be
      undertaken in an individualized manner, a specific treatment does not exist. For
      the treatment, physical methods such as curettage and cryotherapy, topic acids
      (e. g., acetic acid) and alkalis (e. g., potassium hydroxide), some other topical
      agents such as cantharidin and imiquimod, as well as several systemic agents the
      pharmacological treatments is, however, sparse. Effective prevention is
      problematic due to the high infectivity of the virus. A vaccine is not available.

PMID- 23977729
TI  - [Prevention, diagnosis and therapy of the diabetic foot].
AB  - The diabetic foot belongs to the most dreaded complications of diabetes. If
      ulcerations are not treated appropriately, amputations might become necessary.
      But these can be averted by a complex strategy of preventive measures, early
      diagnosis and sufficient treatment.

PMID- 23977730
TI  - [Pharmaceutical care of the geriatric patient in the hospital].

PMID- 23977732
TI  - Equal access to healthcare on a non-discriminatory basis--reality or aspiration?

PMID- 23977733
TI  - The proposed EU-regulation on clinical trials on medicinal products: an unethical
      proposal?
AB  - The Commission has proposed a regulation 'on clinical trials on medicinal
      products for human use' to introduce one regulatory framework for clinical trials
      in the European Union. This regulation should replace the current clinical trials
      directive (2001/20/EC). In this article we describe and critically review the
      main provisions of the proposed regulation. We assess the consequences for a
      sound authorisation procedure of clinical trials and the level of protection for
      human subjects. We note that the proposed regulation is inconsistent with
      applicable international legal documents, such as the Biomedicine Convention and
      the Declaration of Helsinki. We conclude that the proposed regulation does not
      ensure a "high level of human health protection"--required by its legal basis in
      the TFEU--because it may force Member States concerned to accept a reporting
      Member States' approval of--in their estimation--an unethical clinical trial.

PMID- 23977731
TI  - [Not Available].

PMID- 23977734
TI  - Reforming the EU Clinical Trials Directive: streamlining processes or a radical
      "new" agenda?.
AB  - From its conception the EU Clinical Trials Directive met with controversy. Some
      saw it as an unnecessary inhibitor to scientific research, introducing
      bureaucracy which was unduly expensive, slowing down the clinical trial approval
      system. The Directive however also enshrined respect for fundamental rights in
      relation to clinical trials decision-making and impacted upon the domestic law of
      member states facilitating the alignment of trial review processes. Nearly a
      decade after its implementation the EU is moving towards implementation of
      further reform in this area, from a Directive to a Regulation, from a system
      placing the research ethics system at the heart of the clinical trials approval
      committee to one which does not and which represents a see change in
      international and domestic approaches to research ethics. This article critically
      examines the proposed reform of the regulation of clinical trials on medicinal
      product through the introduction of a new EU Regulation and asks whether this can
      be seen as a natural streamlining of processes or a radical new agenda in EU
      health law and regulation.

PMID- 23977735
TI  - Time to address the problem of post-mortem procurement of organs for
      transplantation occurring without proper pre-mortem consent.
AB  - Current cadaveric organ transplant systems allow individuals to be classified as
      donors after death where they registered wishes in favour of this prior to death.
      However, systems for registering wishes pertaining to donation fall woefully
      short of securing proper consent. Furthermore, even jurisdictions which
      technically require consent to be obtained in order to treat an individual as a
      donor, allow that consent to be given by next of kin after death in circumstances
      where there is no evidence of the individual having refused prior to death. This
      article explores these and related issues with current systems from the
      perspectives of health law norms, ethics and human rights. It concludes that
      proper pre-mortem consent ought to be a pre-requisite for post-mortem organ
      transplantation.

PMID- 23977736
TI  - Do consumers have the right to drink healthy wine? An appraisal of the Deutsches
      Weintor case.
AB  - This article seeks to appraise the development that the Deutsches Weintor case
      will bring to EU law concerning health protection. The analysis will be carried
      out by highlighting the structure and the aims of Regulation no. 1924/2006/EC in
      order to assess its role in the construction of health as a fundamental right.
      Furthermore, attention will be devoted to how this judgment could affect the
      general theory behind fundamental rights and how it is placed in relation to the
      settled case law of the Court.

PMID- 23977737
TI  - European Court of Human Right. ECHR 2013/14 Case of Csoma v. Romania, 15 January
      2013, no. 8759/05 (Third Section).

PMID- 23977738
TI  - European Court of Human Rights. ECHR 2013/15 Case of Mehmet Senturk and Bekir
      Senturk v. Turkey, 9 April 2013, no. 14323/09 (Second Section).

PMID- 23977739
TI  - European Court of Human Rights. ECHR 2013/16 Case of Rappaz v. Switzerland, 11
      April 2013, no. 73175/10 (Second Section).

PMID- 23977740
TI  - European Court of Human Rights. ECHR 2013/17 Case of Petukhova v. Russia, 2 May
      2013, no. 28796/07 (First Section).

PMID- 23977741
TI  - European Court of Human Rights. ECHR 2013/18 Case of Gross v. Switzerland, 14 May
      2013, no. 67810/10 (Second Section).

PMID- 23977742
TI  - European Court of Justice. ECJ 2013/14, Eleftherios Themistoklis Nasiopoulos v.
      Ipourgos Igias kai Pronoias, 27 June 2013 (Case C-575/11).

PMID- 23977743
TI  - May I borrow your reputation?

PMID- 23977744
TI  - The American Dental Association and the value of membership.
AB  - The Chair of the ADA Council on Membership presents a snapshot of current
      membership numbers and trends and association membership initiatives. ADA
      programs include advocacy, science to enhance care, a portfolio of member
      benefits, attention to the concerns of young professionals, and a tripartite
      organizational structure.

PMID- 23977745
TI  - The importance of belonging.
AB  - The American Dental Association is actively reaching out to the entire profession
      because of the importance of the profession's speaking with one clear voice. A
      changing context brings new issues and new questions before the profession.
      Without active leadership, dentists and the patients they serve may be short
      changed. The ADA is effectively working on behalf of all of the profession.

PMID- 23977746
TI  - The organization that has our backs.
AB  - A dentist with 16 years of practice experience who participated in the ADA's New
      Dentist program ticks off the benefits of participation in the American Dental
      Association: discounts, insurance, CE, publications, leadership opportunities,
      political voice, patient benefits, product testing, and more.

PMID- 23977747
TI  - ADA Success Dental Student Programs.
AB  - A young general practitioner in Tennessee talks about the rewards of speaking to
      dental students through the American Dental Association's Success Dental Student
      Program and how it reenergizes him and "restocks" the professional waters.

PMID- 23977748
TI  - The ADA is my big practice partner.
AB  - Personal examples are given by a dentist in Michigan of the benefits provided by
      the American Dental Association to practitioners. Of particular importance are
      scientific and professional information that supports treatment and advocacy for
      oral health.

PMID- 23977749
TI  - Leadership in motion.
AB  - Dentists receive many benefits from the formal structure of organized dentistry,
      but the richest rewards come through active participation. This article recounts
      a personal journey in the profession, one where personal growth and the strength
      of the profession intertwine.

PMID- 23977750
TI  - Dentists versus auto mechanics: are there ethical differences?
AB  - The different ethical perspectives of dentists and auto mechanics include primary
      concern, billing procedures, advertising, emergency care, the level of autonomy
      granted to their patients/ clients, the amount of disclosure given to their
      patients/clients, the ability to judge the work of others, and the freedom to
      pursue romantic relationships with their patients/clients. In analyzing these
      differences, one finds dentists to have much greater ethical obligations than
      auto mechanics. There are subtle differences between the ethical expectations of
      Canadian and United States dentists.

PMID- 23977751
TI  - The distressed patient seeking self-harm: autonomy versus beneficence.
AB  - Patient autonomy may conflict with the professional's need to practice
      beneficently. A case is presented showing this conflict. This incompatibility
      between two cardinal virtues in healthcare ethics is analyzed in terms of the
      philosopher Immanuel Kant's dictum that individual autonomy cannot be abridged.
      The tension between these two ethical principles is also discussed in terms of
      the 2008 voter initiative in the State of Washington allowing physician-assisted
      suicide.

PMID- 23977752
TI  - Remembering old lessons in prostate cancer: avoiding errors 'in PARPituity'.

PMID- 23977753
TI  - 'Economies of scale' yield multiple benefits for a private, physician-run
      oncology practice.

PMID- 23977754
TI  - Targeted therapy in the treatment of castration-resistant prostate cancer.
AB  - In the field of metastatic castration-resistant prostate cancer, a bevy of novel
      therapeutics have recently been proven to extend survival via distinct mechanisms
      of action. Although revolutionary, these recent developments have not led to
      improved cure rates, and resistance eventually develops.Thus, further exploration
      into the biologic mechanisms of resistance to these new agents in prostate cancer
      has been necessary. This has opened the door to the development of agents
      designed to manipulate alternative biologic targets. In this review, we focus on
      the testosterone/androgen receptor pathway that is being targeted with potent new
      agents; we also discuss other important alternative biologic pathways that have
      given rise to new therapeutics that may attenuate prostate cancer growth,
      survival, and propagation.

PMID- 23977755
TI  - Targeted therapy in prostate cancer: is there hope beyond the androgen receptor?

PMID- 23977756
TI  - Two paths forward in metastatic castration-resistant prostate cancer.

PMID- 23977757
TI  - Extended surgery for retroperitoneal sarcoma: the key to maximizing the potential
      for cure and survival. Pro.

PMID- 23977758
TI  - Extended surgery for retroperitoneal sarcoma: too much surgery for some and not
      enough for others? Con.

PMID- 23977759
TI  - Management of lymph node-positive prostate cancer: the role of surgery and
      radiation therapy.
AB  - There is no clear consensus on how to manage a subset of patients with prostate
      cancer (PCa) who present with involved lymph nodes (LN+). Although outcomes for
      these patients are uniformly worse than those for patients with localized PCa,
      they are better than outcomes for patients with bone metastases, with more than
      60% of patients alive at 10 years after the initial diagnosis. This article
      reviews the existing data on outcomes for patients treated with various
      combinations of systemic and local therapies. Current evidence suggests both a
      disease-control benefit and a survival benefit to multimodality therapy, which
      combines systemic androgen deprivation therapy (ADT) with local therapies, such
      as surgery and radiation, without evidence of excessive treatment-related
      toxicities.

PMID- 23977760
TI  - Lymph node-positive prostate cancer: the benefit of local therapy.

PMID- 23977761
TI  - N+, M0 prostate cancer: local therapy for systemic disease.

PMID- 23977762
TI  - A large cystic pancreatic mass in a 45-year-old female.

PMID- 23977764
TI  - Weighing the evidence for immune therapy and targeted therapy in renal cancer and
      melanoma.

PMID- 23977763
TI  - High-dose interleukin-2: is it still indicated for melanoma and RCC in an era of
      targeted therapies?
AB  - Immunotherapy with interleukin-2 (IL-2) has been the mainstay of systemic therapy
      for advanced kidney cancer and melanoma. Although IL-2 treatment is limited to
      healthy patients, a select group of these patients have derived substantial,
      durable benefit from it-in some translating into cures with no ongoing therapy or
      chronic toxicity. Over the past 10 years, insights into the biology of renal cell
      carcinoma and into key signaling mechanisms in melanoma, and growth in our
      understanding of immune checkpoints, have led to the development and approval of
      targeted and immune-modulatory therapeutic options with clinically relevant
      benefit. Our improved understanding of the relationship between the host
      environment, immune system, and malignancy has helped identify compounds and
      therapies that are changing the way we think about cancer and our approach to
      cancer therapeutics. While the newer options may be applicable to most patients,
      durable responses measured in years are rare. In this review, we examine the
      currently approved options available for these disease processes, including the
      newer agents and selected combinatorial approaches under investigation, and we
      attempt to identify the role of high-dose IL-2 in the context of current clinical
      practice.

PMID- 23977765
TI  - Is IL-2 still indicated for melanoma and RCC? What a question to ask!

PMID- 23977766
TI  - Can I pray with you?

PMID- 23977767
TI  - Clarifying the use of ruxolitinib in patients with myelofibrosis.
AB  - Myelofibrosis (MF) is a hematopoietic stem cell malignancy classified as a
      myeloproliferative neoplasm (MPN). The clinical course of individuals with MF is
      heterogeneous and characterized by constitutional symptoms, bone marrow
      myeloproliferation and fibrosis, progressive cytopenias, and symptomatic
      splenomegaly. Historically, patients with this debilitating disease have had
      limited treatment options, and disease-modifying agents were not available.
      Hematopoietic stem cell transplantation is the only potentially curative therapy,
      but it is only an option for select patients. The discovery of an activating
      point mutation in the Janus kinase 2 gene (JAK2V617F) in a significant portion of
      patients with MPNs led to improved understanding of the pathobiology of these
      disorders and prompted rapid development of JAK inhibitors. Ruxolitinib (Jakafi)
      is the first-in-class and only JAK inhibitor currently approved by the US Food
      and Drug Administration (FDA) for the treatment of patients with MF; approval was
      based on the results of the COMFORT (COntrolled MyeloFibrosis study with ORal JAK
      inhibitor Treatment) I and II studies. While not a curative option, ruxolitinib
      offers great palliative potential and results in significant reduction in
      splenomegaly and improvement in constitutional symptoms in the majority of
      treated patients, thus improving their quality of life and performance status.
      Additionally, ruxolitinib is the only agent that has demonstrated a survival
      benefit in patients with MF. The optimal use of ruxolitinib for MF patients is
      challenging and complex. In this article, we provide updated data on ruxolitinib
      therapy for patients with MF and offer expert opinion on the appropriate use of
      this agent in the community practice.

PMID- 23977768
TI  - Improving disease burden in myelofibrosis: changing the natural history of the
      disease.

PMID- 23977769
TI  - Ruxolitinib for myelofibrosis: from 'palliation' to prolongation of survival.

PMID- 23977770
TI  - Preventable medical errors: what's the cost?

PMID- 23977771
TI  - Teaching by example: courage, commitment & compassion Diane E. Barag, BS, RNC.
      Interview by Jennifer Neidig.
AB  - While at work, Diane noticed numbing in her hands and was told to visit the
      emergency department. After scans, labs and doctor visits, Diane was diagnosed
      with metaplastic breast cancer, subsequently undergoing 10 rounds of chemo. She
      returned to work wearing her mask and a wig topped with an Eagles hat. After
      returning from blood transfusions or recovering from Nulasta, she never
      complained. Even during troubled times, Diane had her finger on the pulse of her
      unit--recognizing staff achievements, sitting with struggling families and being
      emotionally present for all patients. Diane smiles, she makes others laugh ...
      and while she may not feel well, she is always living. Diane has taught us all to
      care for our patients in such a real way by sharing her story so transparently
      with us. Courage--you define it. Commitment--you embody it. Compassion--you live
      it. You are an extraordinary example of hope, determination and kindness even in
      the hardest of times. We truly thank her for teaching by example!

PMID- 23977772
TI  - Containing a bad flu season.

PMID- 23977773
TI  - The hidden crime: human trafficking.
AB  - As the primary contact in the health care system, nurses can play a role in
      combating this crime and assisting the victims. Assessment for abuse, neglect,
      trauma, recurrent sexually transmitted infections (STIs) and fear of a
      controlling partner is critical. Following up on "red flags" and understanding
      methods of safe questioning can make the difference between slavery and recovery
      for victims. Nurses must also know the professional referrals in their areas once
      a potential victim has been identified. This may be a very dangerous undertaking
      and must be handled by experienced personnel. Referrals to forensic nurses or
      physicians, domestic violence professionals or law enforcement may be indicated.
      Initially, a nurse may want to consult with the agency social worker for
      guidance. Human trafficking is a human rights crime. Unfortunately, it is more
      prevalent in all types of communities than most people suspect. Nurses can be
      heroes to the victims through understanding of this crime and vigilance in the
      assessment and care of all people they encounter in their practices. To learn
      more or to help with this cause, visit the Somaly Mam Foundation at
      www.somaly.org or the U.S. Department of State at www. state.gov.

PMID- 23977774
TI  - Changing the change agents through palliative care education for psycho-oncology
      professionals.

PMID- 23977775
TI  - ACE Project--advocating for clinical excellence: creating change in the delivery
      of palliative care.
AB  - BACKGROUND: Psychologists, social workers, and spiritual care professionals
      report inadequate preparation to maximize their effectiveness in advocating for
      institutional reform to meet oncology patients' diverse bio-psychosocial
      spiritual and cultural needs. This article provides an overview of the ACE
      Project, a National Cancer Institute, 5 year, R25-funded transdisciplinary
      palliative care education program designed to enhance the advocacy and leadership
      skills of 301 competitively selected psycho-oncology professionals. METHODS: ACE
      Project participants identified an institutional goal, refined their goals during
      the course and received mentorship and support throughout the subsequent year.
      Participants were invited to return to a Reunion Conference in year five to
      report on their activities, network, and share the results of their change
      efforts. A subset of 28 ACE Project participants contributed to this OMEGA
      special issue. RESULTS: Participants' goals primarily focused on strategies to
      improve clinical care through program development and improvements in palliative
      care education within their institutions. CONCLUSIONS: The results of this
      transdisciplinary leadership skills-building program for psycho-oncology
      professionals affirm the feasibility and perceived need for the program. See the
      ACE Project website (http://www.cityofhope.org/education/health-professional
      education/nursing-education/ACE-project/Pages/default.aspx) for additional
      program information.

PMID- 23977776
TI  - The development of a sustainable, community-supported children's bereavement
      camp.
AB  - This article describes the creation and development of a sustainable, community
      supported children's bereavement camp. Numerous grief camps were examined prior
      to the project development. The project development was guided by the S.M.A.R.T.
      (S--Strategic/specific; M--Measurable; A--Achievable/attainable; R--Realistic;
      and T--Time-framed) stratagem to direct steps toward the development of the
      bereavement camp. Outcome measures included program participation, as well as
      evaluations completed by campers, family members, and volunteers. Camp attendance
      continues to grow, with 48 children the first year and an average of 65 the
      following 3 years. According to post-evaluation surveys, campers were able to
      integrate back into school with a decrease in stress and an increase in their
      ability to verbalize their grief, share feelings and begin to trust others. One
      child "got her sparkle back" according to her grandmother. Several campers
      commented that camp allowed them to see themselves as normal children. The goal
      of Camp Healing Hearts was that campers would laugh again, and they are.

PMID- 23977777
TI  - Facilitating the provision of quality spiritual care in palliative care.
AB  - In 1948, Dame Cicely Saunders, the founder of the modem hospice movement,
      established a core principle of palliative care, Total Pain, which is defined as
      physical, spiritual, psychological, and social suffering. In 2009, a consensus
      panel (Puchalski, Ferrell, Virani, Otis-Green, Baird, Bull, et al., 2009) was
      convened to address the important issue of integrating spirituality in palliative
      care, which led to renewed efforts to focus on spiritual care as a critical
      component of quality palliative care. This project is a combination of advocacy
      for the importance of spiritual care, training chaplains, seminarians, community
      clergy, and healthcare professionals in palliative care, and creating a spiritual
      care curriculum which can be self-taught or taught to members of
      transdisciplinary teams.

PMID- 23977778
TI  - Building a transdisciplinary approach to palliative care in an acute care
      setting.
AB  - A transdisciplinary team is an essential component of palliative and end-of-life
      care. This article will demonstrate how to develop a transdisciplinary approach
      to palliative care, incorporating nursing, social work, spiritual care, and
      pharmacy in an acute care setting. Objectives included: identifying
      transdisciplinary roles contributing to care in the acute care setting; defining
      the palliative care model and mission; identifying patient/family and
      institutional needs; and developing palliative care tools. Methods included a
      needs assessment and the development of assessment tools, an education program,
      community resources, and a patient satisfaction survey. After 1 year of
      implementation, the transdisciplinary palliative care team consisted of seven
      palliative care physicians, two social workers, two chaplains, a pharmacist, and
      End-of-Life Nursing Consortium (ELNEC) trained nurses. Palomar Health now has a
      palliative care service with a consistent process for transdisciplinary
      communication and intervention for adult critical care patients with advanced,
      chronic illness.

PMID- 23977779
TI  - The impact of additional support services on caregivers of hospice patients and
      hospice social workers.
AB  - Family caregivers often suffer higher levels of physical and emotional distress
      when caring for a chronically or terminally ill family member. Providing this
      kind of care to a loved one at the end of life contributes to increased stress,
      health problems, and a decreased quality of life. The Hospice Caregiver Support
      Project provided support services to caregivers identified by the hospice social
      worker as needing this support and/or assistance. Results from the project show
      that offering additional services relieved caregiver stress by allowing the
      caregiver time away from their caregiving role and reducing feelings of guilt and
      worry, and increased hospice social worker satisfaction with their ability to
      respond to the needs of hospice patients and caregivers.

PMID- 23977780
TI  - Palliative care and use of animal-assisted therapy.
AB  - A growing body of research and clinical reports support the benefits of utilizing
      animal-assisted therapy (AAT) as a complementary, transdisciplinary treatment
      intervention in medical settings. However, fewer articles are found demonstrating
      AAT's use in palliative care settings. This article is a study of the effects of
      AAT in palliative care situations, presenting one anecdotal clinical vignette. In
      this way, the efficacy of this technique in decreasing patient pain, thereby
      increasing patient quality of life, and lowering staff stress levels may be
      illustrated.

PMID- 23977781
TI  - Intentional anticipatory mourning, caregiver and bereavement support program for
      terminally ill veterans, their families & caregivers in the VA Contract Home
      Hospice Program.
AB  - As a response to the increasing numbers of Veterans utilizing the Veterans
      Affairs (VA) Contract Home Hospice Program, and with growing awareness of the
      increased stress at end-of-life, the social work leadership of the Louis Stokes
      Cleveland VA Medical Center implemented a unique approach to support Veterans and
      their families. The role of a grief/bereavement counselor was added to enhance
      the VA Contract Home Hospice Program, to assess the needs of the Veterans and
      family caregivers, and to create a program in response to these findings. A three
      prong module evolved encompassing: Anticipatory Mourning Support for both the
      Veteran and caregiver/ family; Caregiver Support; and Bereavement Support. The
      components of this module are described along with findings in each module.

PMID- 23977782
TI  - A palliative care specific spiritual assessment: how this story evolved.
AB  - This article reflects a project to create, refine, and use a palliative care
      specific spiritual assessment, with the intent to implement its use for both an
      inpatient Palliative Consult Service (PCS) and a Spiritual Health Service (SHS)
      team. Extensive meetings with these services to confirm a shared understanding of
      the use of this spiritual assessment to facilitate communication with PCS through
      consistent language about the patient's story, suffering, spirit, and sense
      making. Following a pilot phase of using this palliative care spiritual
      assessment, five presentations were shared with the SHS team to explore using
      this assessment. Although the SHS team decided not to use its content, these
      presentations spurred dialogue toward what was to become a SHS standardized
      documentation process, eventually called data, intervention, outcome, plan
      (DIOP).

PMID- 23977783
TI  - Last watch: developing an inpatient palliative volunteer program for U.s.
      Veterans in hospice.
AB  - This project offers encouraging evidence of the impact of providing companionship
      and compassionate care to actively dying Veterans. Veteran-centered care serves
      as a guide for volunteer program objectives including goals based on measuring
      outcomes of volunteer visits offered to Veterans, frequency of visits to those
      desiring volunteer involvement and documentation of goals on the resident plan of
      care. Forty-eight Veterans were admitted to the Palliative Integrated Care (PIC)
      Unit during the project review period with a median length of stay (LOS) of 7
      days, ranging 1-50 days. Goals were met for Veterans with LOS > 3 days; however,
      it was more challenging to meet the needs of Veterans with shorter stays. Data
      for this project were collected over a 6-month period. The U.S. Department of
      Veterans Affairs (VA) is responding to the needs of end-of-life Veterans who do
      not have family or friends readily available through the No Veteran Dies Alone
      initiative.

PMID- 23977784
TI  - Improving access and satisfaction with spiritual care in the hospice setting.
AB  - Hospice of Sacred Heart, an agency of PeaceHealth Oregon, experienced a dramatic
      increase in its census beginning in 2007. The spiritual care team noticed the
      number of referrals was decreasing while the census was increasing. A quality
      improvement initiative was conducted, including a staff survey, an education
      program about spirituality and the role of chaplains on interdisciplinary teams
      in the hospice setting, and an audit of the chaplain's daily allocation of time.
      These actions resulted in an increase in the use of spiritual care services by
      patients and staff and the addition of two full-time, benefited chaplain
      positions.

PMID- 23977785
TI  - Northwest cancer specialists (ncs) cares: coordinated, advocacy, resources,
      education, and support: a palliative care program in an outpatient oncology
      practice.
AB  - A large community-based oncology practice developed a pilot project to enhance
      staff and patient awareness of the benefits of palliative care, advance care
      planning, and earlier intervention with patients with advancing disease. The
      results were ongoing implementation of palliative care conferences at all sites,
      greater numbers of referral to hospice, lessened chemotherapy given in the last 2
      weeks of life, and the hiring of two social workers as a result of needs
      identified. Staff reported greater satisfaction with interprofessional
      communication.

PMID- 23977786
TI  - Strengthening end-of-life care for African-American patients and families through
      education and community outreach.
AB  - Care for African-American patients and families at the end of life presents a
      unique challenge to healthcare providers. Providers need to be culturally and
      historically competent to effectively serve persons with a long history of
      distrust of the white-dominated healthcare system. Effective means of addressing
      outreach, access, and service issues for this community need to be twofold. They
      must focus on those who deliver the care and those who receive it. This twofold
      focus inspired the education and community outreach that were key elements in
      this ACE Project. The resources of the Duke Institute on Care at the End of Life
      (ICEOL), particularly their APPEAL curriculum, was key to strengthening end-of
      life care in the internal culture of Abington Memorial Hospital and the community
      they serve.

PMID- 23977787
TI  - Bereavement: caring for families and friends after a patient dies.
AB  - New York-Presbyterian Hospital/Weill Cornell Medical Center is a large academic
      medical center that provided minimal, if any, bereavement support to families and
      loved ones of patients who died in the hospital. A comprehensive bereavement
      program was developed and implemented which included sending condolence cards to
      family members and friends, follow-up phone calls to screen for complicated
      grief, individual counseling, bereavement support groups, community referrals,
      and an annual memorial service for families and staff to provide an opportunity
      for shared mourning during the grieving process.

PMID- 23977788
TI  - Improving the integration of palliative care in a comprehensive oncology center:
      increasing primary care referrals to palliative care.
AB  - Confronted with the complexities inherent in delivering palliative care,
      effective collaboration with referring staff becomes vital. Based on the
      evaluation of the physical and psychosocial concerns of patients, the goal of
      palliative care is to craft interventions that maintain quality of life in the
      face of increasing symptoms and deteriorating functional status. The project's
      goal was to increase the appropriateness of referrals to palliative care by the
      primary services in the hospital. The aim was to achieve this by developing a
      process to assess patient functioning in critical psychosocial and functional
      areas, and providing this data to referring medical staff to educate them on the
      contribution of palliative care to symptom control and patient quality of life.
      The findings show that referrals to palliative care have increased over 100% from
      a broader range of services since initiating this project. Assessment data has
      been collected on 165 patients and outcomes are discussed.

PMID- 23977790
TI  - The forgotten educational needs of the house staff: training internal medicine
      residents to address end-of-life issues.
AB  - An intervention was conducted, aimed at providing residents in internal medicine
      with communication skills to address end-of-life issues with patients. Residents
      participated in two 1-hour educational sessions designed to teach a communication
      protocol, enhance listening skills, and to provide practice in effective
      communication in a safe, small-group format. An anonymous on-line survey assessed
      the effectiveness of the intervention. Twenty-five residents completed the
      intervention. There was a trend toward increased comfort level in addressing end
      of-life issues among residents who completed the intervention, versus a
      comparison group. Residents who completed the intervention reported that using
      the words "death" and "dying" with patients and families was an important
      teaching point.

PMID- 23977789
TI  - Translating dignity therapy into practice: effects and lessons learned.
AB  - Dignity Therapy (DT) is an intervention designed to lessen existential suffering
      as death draws near. DT has a growing evidence base, with positive outcomes for
      patients and their family members; however, it is not yet widely available in
      community settings. The purpose of this project was to translate DT into clinical
      practice in a cancer center in the midwestern United States. DT was provided to
      10 patients with metastatic cancer who completed baseline and post-intervention
      measures of depression, existential distress, health-related quality of life, and
      satisfaction with the intervention. DT was found to be feasible and acceptable to
      the majority of patients and their families. DT outcomes will be presented, along
      with suggestions for clinicians who are interested in offering DT in their
      practices.

PMID- 23977791
TI  - Improving incidence of referrals for psychosocial and spiritual transdisciplinary
      care in a palliative care service: focus on brain death.
AB  - The goal of this project was to examine the uniformity of the hospital's delivery
      of psychosocial and spiritual care for the families of patients being evaluated
      for brain death. A retrospective chart review encompassing one calendar year was
      conducted. After conferring with physicians and staff, a strategy was developed
      to capture information on patients who were diagnosed with brain death. Following
      evaluation of the information gathered, a proposal was introduced and hospital
      procedure revised. Triggers were put in place to ensure consistent offering of
      psycho-spiritual transdisciplinary services to the families of patients who are
      undergoing evaluation for brain death.

PMID- 23977792
TI  - Improving end-of-life care for ventricular assist devices (VAD) patients: paradox
      or protocol?*.
AB  - When a person consents to have a ventricular assist device (VAD) implanted in
      one's heart, the intention is to extend life toward a new heart or toward more
      time. Complications may develop followed by frequent hospital admissions-most
      often in an intensive care unit (ICU) setting-rendering a transplant a distant
      reality and to discontinue the device means certain death. Emotional support for
      patient and family is critical. Regardless of the original goal for the device,
      palliative care provides assistance in communication, goal setting, and symptom
      management and yet its consultation is often more for brink-of-death care than
      end-of-life care provided at the time of diagnosis of a life-threatening disease
      such as heart failure. This study examined the recent deaths of hospitalized
      patients with VADs and the use of the palliative care service. Understanding the
      benefit and timing of palliative care for VAD patients-particularly in the ICU
      setting--may improve the end-of-life experience for patients, families, and
      healthcare providers.

PMID- 23977793
TI  - Psychosocial concerns among Latinas with life-limiting advanced cancers.
AB  - Research has demonstrated that limited dialogue in end-of-life (EOL) care can
      negatively impact decision-making and place of death. Furthermore, when
      vulnerable populations are faced with EOL cancer care, they experience issues
      resulting from previous gaps in services attributed to sociocultural and economic
      issues that influence EOL care. These conditions place an additional burden on
      disadvantaged populations which can cause distress, especially as disparate
      conditions continue to persist. Little is known about Latinos' psychosocial
      concerns that lead to distress in EOL care. The objective of this study is to
      explore Latinas' experiences with life-limiting cancer conditions to identify the
      EOL care concerns that impact their dying experience. This study used a
      phenomenological approach to explore the EOL care concerns of 24 Latinas
      receiving treatment for metastatic cancers in a public sector healthcare system
      in Los Angeles, California. In-depth interviews were recorded and transcribed,
      and qualitative analysis was performed using Atlas.ti software.

PMID- 23977794
TI  - Examining the impact of spiritual care in long-term care.
AB  - This project examines the effects of spiritual care on chronically ill and aging
      populations and those who care for them by studying the development of a
      comprehensive Pastoral Care Program at Episcopal Communities & Services (ECS), a
      nonprofit that owns two Continuing Care Retirement Communities (CCRC) in Southern
      California (in 2010 ECS operated three communities). The study includes the
      vision, methodology, and specific steps taken to implement this spiritual care
      program and methods to measure its efficacy. Data is analyzed from satisfaction
      surveys conducted the year before the program's introduction and surveys taken 2
      and 4 years after the institution of the Pastoral Care Program, along with
      anecdotal findings. Results indicated that spiritual awareness and satisfaction
      increased throughout the resident population after the Pastoral Care Program's
      establishment and that satisfaction levels continued to improve as the program
      developed over time. This study suggests that spiritual support (both religious
      and nonreligious) is a vital factor in well-being and quality of life at the end
      of life and that transdisciplinary palliative care is needed in long-term care
      settings to address spiritual and psychosocial needs.

PMID- 23977795
TI  - Advocating and educating for spiritual screening assessment and referrals to
      chaplains.
AB  - This article presents attempts to improve the quality of spiritual care offered
      to palliative care patients by educating nursing and other staff about spiritual
      screening with the goal of increasing referrals to a board certified chaplain.
      Attention to patients' spiritual identity and spiritual needs upon admission and
      throughout a hospitalization through either a formalized screening tool or
      provider awareness and sensitivity can assist patients in naming their needs,
      thus triggering a referral to a board certified chaplain or other spiritual
      counselor. Along with a spiritual care plan based upon assessment of spiritual
      needs and resources facilitates the healing process.

PMID- 23977796
TI  - Bridging the communication gap in hospice and palliative care for Hispanics and
      Latinos.
AB  - The Hispanic and Latino populations have increased nationwide. Hispanics are now
      the largest minority group in the United States. This increase in population will
      have an impact on all service areas, including hospice and palliative care. The
      goal as service providers is to remove barriers to care in order to increase
      opportunities for all the people residing in the communities. This project
      addresses the impact of the Hispanic and Latino populations in Pasco County,
      Florida, and the need to develop Latino outreach programs that will inform,
      educate, and provide culturally sensitive services which will decrease the
      barriers of communication and accessibility for Hispanics and Latinos who are in
      need of hospice and palliative care. The new outreach program, named Nuestro,
      which means "ours" in Spanish, is designed with this purpose in mind. The
      project's goal was to increase service by 200%; the outcome after 2 years was an
      increase of services by 900%.

PMID- 23977797
TI  - Weaving interdisciplinary and discipline-specific content into palliative care
      education: one successful model for teaching end-of-life care.
AB  - While palliative care is best delivered in an interdisciplinary format, courses
      teaching the interdisciplinary approach to palliative care are rare in healthcare
      education. This article describes a graduate-level course in palliative care for
      students in nursing, pharmacy, social work, and gerontology taught by faculty
      from each discipline. The overarching goals of this course are to convey core
      palliative care knowledge across disciplines, articulate the essential
      contribution of each discipline in collaborative care, and to define
      interdisciplinary processes learners need to understand and navigate
      interdisciplinary palliative care. Learning outcomes included increased knowledge
      in palliative care, enhanced attitudes in practice and application of skills to
      clinical practice settings, increased ability to contribute discipline-specific
      knowledge to their teams' discussions, and a sense of increasing confidence in
      participating in the care of complex patients, communicating with families, and
      contributing to the team as a member of their own discipline.

PMID- 23977798
TI  - Striving for wholeness and transdisciplinary teamwork at a pacific basin's pain
      and palliative care department.
AB  - Collaborations in palliative care have helped to create a framework and identify
      preferred practices so the field of palliative care can grow. Teamwork designed
      in a transdisciplinary style is desired and provides whole-person, sensitive, and
      comprehensive care. In applying the basic key concepts and evidenced-based
      knowledge of palliative care, this article details one palliative care
      department's effort to create change, enhance the delivery of care, and build
      their palliative care practice. Creating collaborations and building partnerships
      were fundamental outcomes to improve the palliative care practice, increase
      transdisciplinary teamwork activities, and enhance the delivery of care in this
      organization.

PMID- 23977799
TI  - Vanderbilt-Ingram Cancer Center's & Gilda's Club Nashville: Songs from the Heart.
AB  - Songs from the Heart is an annual palliative care and outreach/support project
      done in partnership with the Vanderbilt-Ingram Cancer Center Henry Joyce Cancer
      Clinic and Gilda's Club Nashville. It is a two-evening songwriters' workshop and
      concert that gives cancer survivors, family members and healthcare professionals
      the opportunity to tell their story about cancer through the art of music in a
      safe therapeutic environment, It is a unique project through the art of music
      helping others of all ages and from all walks of life find healing and hope; as
      well as an opportunity to give back to others. A professional singer/songwriter
      and a social worker co-facilitate the two-evening songwriters workshop. Two
      musicians perform songs the workshop songwriters have written at a community wide
      concert. Those who have participated in Songs from the Heart have communicated
      through the workshop evaluations that this experience has been life changing and
      a unique opportunity in being able to: explore and express their deep felt
      emotional feelings and thoughts; release their creative juices; ability to be
      alone with the group, yet feel included as a whole; express their journey through
      music; and benefit from being involved with others affected by cancer who have
      had similar difficulties. Others who have attended the concert or listened to the
      CD have expressed the significant impact these songs have had on their lives and
      their journey with cancer.

PMID- 23977800
TI  - The "We Care" program for long-term care: providing family members with support
      following the death of a loved one.
AB  - Although bereavement programs in hospice and palliative care settings are known
      to produce positive outcomes for family members after the death of a loved one,
      currently there is a clear lack of services offered through long-term care (LTC)
      facilities, where older adults often reside prior to their death. The purpose of
      the present article is to present an initial bereavement program called We Care
      that focused on providing additional support for family members who experience a
      death of a loved one while in a LTC facility. Goals for the program include: 1)
      providing ongoing contact with the family for 1 year, and 2) offering a
      bereavement group. The program's model is explained, with highlights of obstacles
      experienced and suggestions for future programs.

PMID- 23977801
TI  - Use of complementary therapies in hospice and palliative care.
AB  - As society has become increasingly inquisitive about complementary therapies,
      various sectors of the medical community have begun to incorporate complementary
      therapies into their practice, studying their impact on client health and
      effectiveness in treating specific symptoms. This article describes the design
      and initial findings from a 1-year review of the implementation of massage and
      Reiki therapies on patients in a small hospice and palliative care program in
      central Connecticut. Over the course of 1 year, 114 massage sessions were
      provided to 52 different patients, all of which included Reiki. After completion
      of these sessions, patients were evaluated for changes in symptoms such as pain
      reduction, ease in breathing, stress/anxiety reduction, and increased relaxation,
      with the results being predominantly beneficial.

PMID- 23977802
TI  - Improving a grief and loss program: caring for patients, families, and staff.
AB  - The University of Michigan Comprehensive Cancer Center (UMCCC) Grief and Loss
      Program provides supportive care services during bereavement which is considered
      part of the care continuum. This program received 50 death notifications per
      month upon project initiation and currently receives approximately 125 per month.
      Initial program evaluation was conducted via a pilot survey of bereaved parents
      as well as verbal and written evaluations from the transdisciplinary staff of
      Patient and Family Support Services. Grief support prior to evaluation included
      mailings, phone calls as indicated, poorly attended bereavement support groups,
      and limited staff support. Based on program evaluation, grief support continues
      through the use of mail/e-mail and phone calls to those at risk for complicated
      grief Three to four gatherings per year are offered rather than monthly support
      groups, and connections to community resources are provided. The Comfort And
      Resources at End of Life (C-A-R-E) program was implemented to support and educate
      staff. Next steps include further program evaluation and potential research to
      examine best practices for the bereaved.

PMID- 23977803
TI  - Home hospice care and the arts: Arts @ the Bedside.
AB  - The arts, in their multiplicity of forms, have shown to be of benefit to patients
      in healthcare settings and their family members. Benefits can include expression,
      relaxation, and distraction. Arts @ the Bedside, an initiative of the Visiting
      Nurse Service of New York Hospice Care, sought to train hospice volunteers with
      an art background, or interest, to safely and confidently introduce the arts in a
      variety of mediums to hospice patients and families. Monthly trainings sessions,
      led by professional artists, were offered to volunteers. Volunteers who
      participated in six or more trainings received a "Certificate of Completion." The
      number of volunteer art visits, session reports, and the impact on volunteers
      were recorded. Qualitative data suggests that patients, staff, and volunteers
      gain from the introduction of the arts in home hospice care.

PMID- 23977804
TI  - [Wageningen and Utrecht as natural partners].

PMID- 23977805
TI  - [Pulling on a ...].

PMID- 23977806
TI  - [VvAA starts MBA for health professionals].

PMID- 23977807
TI  - [Trends from the GD-monitoring].

PMID- 23977808
TI  - [Opinions about the veterinary business guidance of yes-or-no managed dairy
      farms].

PMID- 23977809
TI  - A previously unknown mechanism in viral pathogenesis leading to effective new
      vaccines and post-exposure immune treatments of viral infections.
AB  - Investigations with the rabies virus identified a previously unknown mechanism of
      viral pathogenesis. After ultracentrifugation of a suspension of rabid dog brain
      and rabies vaccine strains, the supernatant was found to contain active
      components, as evaluated in an in vitro plaque test. The unexpected detection of
      active components in non-sedimented material prompted further research and the
      finding that these components, and not the complete virus, were responsible for
      paralysis and death. Vaccination of cattle with existing rabies vaccines showed
      that even low titres of antibodies against these components provided protection
      after challenge. In a control group of non-vaccinated cows, cows that had low
      titres of these antibodies survived rabies challenge. These low titres could not
      be detected with the usual serum neutralization test in mice but only with a
      plaque reduction test, which is more sensitive. A hyperimmune serum raised in
      rabbits against active components isolated from the brain of a rabid dog was
      injected intracerebrally into mice that had been previously injected
      intramuscularly with a rabies virus. This delayed post-exposure treatment was
      still effective against advanced rabies (virus already in the brain, but not yet
      paralytic symptoms). This promising finding makes the development of a new
      inactivated rabies vaccine possible and opens the way for post-exposure treatment
      for humans, particularly in developing countries where rabies is still a major
      problem. The role of these active components in other viral diseases, such as
      human immunodeficiency virus, should be investigated.

PMID- 23977810
TI  - [Why Giardia is so hard to eradicate].

PMID- 23977811
TI  - [Better evidence based decision making].

PMID- 23977812
TI  - [Accomplishing more with interprofessional communication].

PMID- 23977813
TI  - [Development path veterinary management: 'I took a lot of extra training'].

PMID- 23977814
TI  - ['With every dog we engage in discussion'].

PMID- 23977815
TI  - The impact of physical and psychological comorbid conditions on the quality of
      life of patients with acute myocardial infarction: a multi-center, cross
      sectional observational study from Turkey.
AB  - OBJECTIVE: Acute myocardial infarction (MI) has significant and detrimental
      effects on the lifestyles of the patients. It has been shown that quality of life
      (QoL) in patients with MI is impaired in every aspect. This study aims to
      evaluate the impact of depression and physical comorbidity on QoL in Turkish
      patients with acute first MI. METHOD: This multi-center cross-sectional study was
      carried out in 15 centers with 998 patients hospitalized for acute first MI. For
      detection of depression, Beck Depression Inventory (BDI) was used. For evaluation
      of QoL, World Health Organization Quality of Life Questionnaire (WHOQOL) was
      applied. RESULTS: The mean age of the patients was 57.5 +/- 10.1 years and 79.2 %
      (n = 792) of the patients were men. Patients with comorbid depression (BDI > or =
      10) and comorbid medical conditions, and female patients had significantly lower
      scores in every domain of WHOQOL. In the regression analysis model, female
      gender, low education, comorbid medical conditions, especially comorbid
      hypertension, and BDI score were found to have a significant effect on the
      domains of WHOQOL. CONCLUSIONS: Female patients are more prone to impairment in
      quality of life after myocardial infarction. Both comorbid medical conditions and
      depression have a significant impact on the impairment of QoL in Turkish patients
      with acute MI. In order to improve the subjective wellbeing of post MI patients,
      both psychiatric and physical comorbidities must be detected and managed even in
      the short-term.

PMID- 23977816
TI  - Effectiveness of prolonged exposure for PTSD in older veterans.
AB  - Exposure-based therapy is an effective treatment for PTSD, including combat
      related PTSD. However, questions remain within PTSD treatment literature and
      among front-line clinicians about the appropriateness of exposure-based therapies
      for older adults. The current study examined the effectiveness of Prolonged
      Exposure (PE) in reducing PTSD and depression symptoms in a sample of 65 Veterans
      age 60 and older who were diagnosed with PTSD via structured clinical interview.
      In addition to within-subject repeated measure analyses, the entire intent to
      treat sample was compared to treatment completers. Within group d-type effect
      sizes across both groups were large (1.13-1.90) and the retention rate was high
      (85%). Importantly, no adverse medical or psychiatric events were reported over
      the course of the study. Results are discussed and limitations, along with future
      directions, are presented.

PMID- 23977817
TI  - Switching to ziprasidone in the clinical practice setting: an open-label study.
AB  - OBJECTIVE: This observational study evaluates the long-term outcome of switching
      to ziprasidone in patients with schizophrenia in the clinical practice setting.
      METHODS: Patients (208) with schizophrenia who had been switched to ziprasidone
      monotherapy due to partial response or tolerability problems were followed for 1
      year. Efficacy was assessed at baseline and months 1, 3, and 12 with Brief
      Psychiatric Rating Scale (BPRS), Clinical Global Impression-severity (CGI-S), and
      CGI-improvement. Quality of life, functionality, and safety measures, including
      metabolic parameters, were also assessed; 195 subjects comprised the per protocol
      analysis population. RESULTS: A reduction > or = 30% in BPRS total score was
      observed in 42.5% of the subjects. Mean scores of the BPRS (global and positive
      and negative clusters), CGI-S and CGI-I significantly decreased at endpoint (p <
      0.001). Ziprasidone treatment was also associated with statistically significant
      improvements in the GAF, WHO-DAS-II, and SF-12. After 1-year follow-up, a mean
      weight decrease of -1.6 kg (p < 0.05) was observed. Mean levels of LDL
      cholesterol and triglycerides also decreased (p < 0.01) while HDL cholesterol
      levels increased (p < 0.05) at endpoint. No significant changes in mean glucose
      levels at study end were detected. CONCLUSION: These findings suggest that
      switching to ziprasidone is effective and well tolerated in patients with
      schizophrenia requiring a change in antipsychotic medication.

PMID- 23977818
TI  - Perioperative psycho-educational intervention can reduce postoperative delirium
      in patients after cardiac surgery: a pilot study.
AB  - OBJECTIVE: Postoperative delirium after cardiac surgery is associated with many
      consequences such as poorer functional recovery, more frequent postoperative
      complications, higher mortality, increased length of hospital stay, and higher
      hospital costs. The aim of this study was to evaluate the efficacy of
      perioperative psycho-educational intervention in preventing postoperative
      delirium in post cardiac surgery patients. METHOD: We conducted a comparative
      retrospective study between 49 patients who had received perioperative psycho
      educational intervention and 46 patients who had received standard care. The
      primary outcome was the incidence of postoperative delirium. Secondary outcomes
      included length of ICU stay, and severity and duration of postoperative delirium
      among the patients who had developed delirium. RESULTS: The incidence of
      postoperative delirium was significantly lower in the intervention group than
      that in the control group (12.24% vs. 34.78%, P = 0.009). Among the patients who
      had developed postoperative delirium, there was no statistical difference between
      the two groups regarding secondary outcomes. CONCLUSIONS: Our results show that
      the patients who received perioperative psycho-educational intervention were
      associated with a lower incidence of postoperative delirium after cardiac surgery
      than those who received standard care. Clinicians would be able to implement this
      psycho-educational intervention as part of routine practice to reduce delirium.

PMID- 23977819
TI  - Forty days after the Great East Japan Earthquake: field research investigating
      community engagement and traumatic stress screening in a post-disaster community
      mental health training.
AB  - The current article describes the results of posttraumatic stress educational
      outreach and screening offered to 141 citizens of Japan who attended a public
      service mental health training regarding post-disaster coping 40 days after a 6.8
      Richter Scale earthquake, local and regional deaths, and an ongoing nuclear
      radiation threat. Attendees were given access to anonymous questionnaires that
      were integrated into the training as a tool to help enhance mental health
      literacy and bridge communication gaps. Questionnaires were turned in by a third
      of those in attendance. Among respondents, multiple exposures to potentially
      traumatic events were common. More than a quarter of respondents met criteria for
      probable PTSD. Physical health and loss of sense of community were related to
      PTSD symptoms. Associations and diagnosis rates represented in these data are not
      generalizable to the population as a whole or intended for epidemiological
      purposes; rather, they are evidence of a potentially useful approach to post
      disaster clinical screening, education, and engagement. Results are presented in
      the context of previous findings in Japan and ecologically-supportive post
      disaster field research is discussed.

PMID- 23977820
TI  - Competence of medical students and residents in psychiatry regarding
      spirituality, at a South African school of clinical medicine.
AB  - OBJECTIVE: Elsewhere, curricula for undergraduate and postgraduate psychiatry
      have been extended to include the role of spirituality. It has also become
      important to establish how, within accepted professional boundaries, spirituality
      should be incorporated appropriately into the current model for South African
      practice and training. The objectives included exploring, analyzing, and
      describing the views and experience of local academic psychiatrists on this
      topic. METHODS: This study was designed as an explorative, descriptive,
      phenomenological qualitative investigation. In-depth, semi-structured interviews
      were conducted with individual academic specialist psychiatrists as the primary
      data source. RESULTS: Data saturation was achieved after 13 interviews. "Training
      of spirituality in psychiatry" emerged as one of six main themes from the
      integrated interview and literature content. All participants proposed that
      spirituality must be included in undergraduate medical and specialist psychiatric
      training. They have suggested that a mentorship model should be considered, which
      implies the reorientation of the teachers of psychiatry in this regard.
      CONCLUSIONS: This view concurred with the international medical literature,
      recommending that spirituality has to be incorporated into specialist psychiatric
      practice and training, but within professional boundaries and with all faith
      traditions and belief systems considered equally.

PMID- 23977822
TI  - Trap and transfer. two-step hole injection across the Sb2S3/CuSCN interface in
      solid-state solar cells.
AB  - In solid-state semiconductor-sensitized solar cells, commonly known as extremely
      thin absorber (ETA) or solid-state quantum-dot-sensitized solar cells (QDSCs),
      transfer of photogenerated holes from the absorber species to the p-type hole
      conductor plays a critical role in the charge separation process. Using Sb2S3
      (absorber) and CuSCN (hole conductor), we have constructed ETA solar cells
      exhibiting a power conversion efficiency of 3.3%. The hole transfer from excited
      Sb2S3 into CuSCN, which limits the overall power conversion efficiency of these
      solar cells, is now independently studied using transient absorption
      spectroscopy. In the Sb2S3 absorber layer, photogenerated holes are rapidly
      localized on the sulfur atoms of the crystal lattice, forming a sulfide radical
      (S(-*)) species. This trapped hole is transferred from the Sb2S3 absorber to the
      CuSCN hole conductor with an exponential time constant of 1680 ps. This process
      was monitored through the spectroscopic signal seen for the S(-*) species in
      Sb2S3, providing direct evidence for the hole transfer dynamics in ETA solar
      cells. Elucidation of the hole transfer mechanism from Sb2S3 to CuSCN represents
      a significant step toward understanding charge separation in Sb2S3 solar cells
      and provides insight into the design of new architectures for higher efficiency
      devices. 

PMID- 23977821
TI  - Association of anxiety and depression with pulmonary-specific symptoms in chronic
      obstructive pulmonary disease.
AB  - OBJECTIVES: To examine the association of anxiety and depression with pulmonary
      specific symptoms of Chronic Obstructive Pulmonary Disease (COPD), and to
      determine the extent to which disease severity and functional capacity modify
      this association. METHOD: Patients (N = 162) enrolled in the INSPIRE-II study, an
      ongoing randomized, clinical trial of COPD patients and their caregivers who
      received either telephone-based coping skills training or education and symptom
      monitoring. Patients completed a psychosocial test battery including: Brief
      Fatigue Inventory, St. George's Respiratory Questionnaire, UCSD Shortness of
      Breath Questionnaire, State-Trait Anxiety Inventory, and Beck Depression
      Inventory. Measures of disease severity and functional capacity (i.e., FEV1 and
      six-minute walk test) were also obtained. RESULTS: After covariate adjustment,
      higher anxiety and depression levels were associated with greater fatigue levels
      (ps < .001, deltaR2 = 0.16 and 0.29, respectively), shortness of breath (ps <
      .001, deltaR2 = 0.12 and 0.10), and frequency of COPD symptoms (ps < .001,
      deltaR2 = 0.11 and 0.13). In addition, functional capacity was a moderator of
      anxiety and pulmonary-specific COPD symptoms. The association between anxiety and
      shortness of breath (p = 0.009) and frequency of COPD symptoms (p = 0.02) was
      greater among patients with lower functional capacity. CONCLUSIONS: Anxiety and
      depression were associated with higher levels of fatigue, shortness of breath,
      and frequency of COPD symptoms. It is important for clinicians to be aware of the
      presence of anxiety and depression in COPD patients, which appears to correlate
      with pulmonary-specific COPD symptoms, especially in patients with lower
      functional capacity. Prospective design studies are needed to elucidate the
      causal relationships between anxiety and depression and pulmonary-specific
      symptoms in COPD patients.

PMID- 23977823
TI  - Response to comment on purification and characterization of chromium-binding
      substance from high-chromium yeast.

PMID- 23977824
TI  - Electrorheology of suspensions containing interfacially active constituents.
AB  - We recently showed that a suspension of micrometer-sized polystyrene (PS)
      particles in a PDMS liquid, mixed with small (1 wt %) amounts of a nanocage,
      sulfonated polyhedral oligomeric silsesquioxane (s-POSS), exhibited significant
      electrorheological (ER) behavior. This behavior was associated with the formation
      of a thin adsorbed layer of s-POSS onto the surfaces of PS and the subsequent
      formation of polarization-induced aggregates, or structures, responsible for the
      ER effect in an applied electric, E, field. Current theory suggests that the ER
      effect would largely be determined by the dielectric and conductive properties of
      the conductive layer of core/shell particles in ER suspensions. We show here that
      sulfonated-PS (s-PS)/PDMS suspensions exhibit further increases in the yield
      stress of over 200%, with the addition of s-POSS. The yield stress of this
      system, moreover, scales as tauy [proportionality] E(2). The dielectric
      relaxation studies reveal the existence of a new relaxation peak in the s-POSS/s
      PS/PDMS system that is absent in the s-POSS/PS/PDMS suspension. The relative
      sizes of these peaks are sensitive to the concentration of s-POSS and are
      associated with changes in the ER behavior. The properties of this class of ER
      fluids are not appropriately rationalized in terms of current theories.

PMID- 23977825
TI  - Understanding of the unique risks of CVD that women face. Foreword.

PMID- 23977826
TI  - Cardiovascular disease in women: reducing cardiovascular comorbidity.
AB  - Cardiovascular disease is the leading etiology of mortality in women. The
      American Heart Association recommends classifying a woman's risk as 1 of 3
      categories: ideal cardiovascular health, at risk, and high risk. Risk levels are
      based on traditional risk factors, such as lipid levels, blood pressure, body
      mass index, and smoking status. Risk can be assessed using the Framingham risk
      score, which estimates an individual's 10-year risk of myocardial infarction or
      stroke. Other risk factors for cardiovascular disease that should be considered
      include psychosocial disadvantage, marital status, depression, and anxiety. A
      multidisciplinary approach to managing these stressors may decrease
      cardiovascular morbidity and mortality. 

PMID- 23977827
TI  - Cardiovascular disease in women: heart disease across the life span.
AB  - Women are more likely to have atypical cardiovascular symptoms compared with men.
      This may lead to delayed diagnosis of coronary artery disease (CAD) and
      suboptimal treatment. The exercise stress test is the initial test for women with
      suspected or known CAD. The addition of imaging (eg, echocardiography, nuclear
      medicine, computed tomography scan, magnetic resonance imaging) to the exercise
      component may improve the diagnostic value of the test. Drugs used to manage CAD
      in women include antiplatelets, beta blockers, lipid-lowering drugs, angiotensin
      converting enzyme inhibitors, calcium channel blockers, and nitrates. Invasive
      therapy with angioplasty or bypass surgery is performed less frequently in women
      than in men. Women may present with acute coronary syndrome and atypical
      symptoms. Initial treatment should be the same for men and women. Takotsubo
      cardiomyopathy is a rare condition that is seen more frequently in older,
      postmenopausal women. 

PMID- 23977828
TI  - Cardiovascular disease in women: peripheral artery disease.
AB  - Peripheral artery disease (PAD) is a common vascular disease in women that is
      underrecognized. It is most strongly associated with smoking and diabetes. Women
      with PAD are more likely to have atypical or no symptoms compared with men. The
      classic symptoms of claudication are seen in some, but not all, patients. The
      most useful initial test for PAD is the ankle-brachial index. The American
      College of Cardiology Foundation/American Heart Association guideline recommends
      that it be obtained for all patients with exertional leg symptoms; patients 50
      years or older with diabetes; patients 50 years or older who smoke; all patients
      older than 65 years; and any patient with known coronary artery disease. Other
      tests, such as Doppler ultrasonography, magnetic resonance angiography, and
      computed tomography angiography, should be reserved for patients in whom the
      diagnosis of PAD is unclear. Exercise programs improve symptoms. Aspirin and
      statins are recommended for all patients with PAD, whereas surgery is reserved
      for patients who do not benefit from medical therapy. 

PMID- 23977829
TI  - Cardiovascular disease in women: contraceptive issues and nonvalvular
      cardiovascular disease.
AB  - Several reproductive issues affect cardiovascular risk in women. Polycystic ovary
      syndrome is common and may include menstrual irregularities, hirsutism, and
      metabolic symptoms. Patients with this syndrome have an increased risk of
      impaired glucose tolerance and dyslipidemia. Hysterectomy is a common gynecologic
      surgery that may affect estrogen levels in women. There are conflicting data on
      the cardiovascular risk associated with estrogen use in women after a
      hysterectomy. Human papillomavirus is a newly identified risk factor for
      cardiovascular disease (CVD), but the mechanism and effect are still unknown.
      Contraceptives are the most commonly used prescription drugs among women in the
      United States. The absolute risk of CVD in young women is low; therefore, the
      threefold increase in risk that is associated with contraceptives is still low.
      Estrogen is thought to be the primary concern related to the increased
      cardiovascular risk associated with combined oral contraceptives. Contraceptive
      pills also may affect insulin, lipid, and blood pressure levels. 

PMID- 23977831
TI  - Effect of low frequency (LF) electric fields on gene expression of a bone human
      cell line.
AB  - We evaluated the effects, on cultured human SaOS-2 cells, of exposures to the low
      frequency (LF) electric signal (60 kHz sinusoidal wave, 24.5 V peak-to-peak
      voltage, amplitude modulated by a 12.5 Hz square wave, 50% duty cycle) from an
      apparatus of current clinical use in bone diseases requiring regenerating
      processes. Cells in flasks were exposed to a capacitively coupled electric field
      giving electric current density in the sample of 4 uA/cm(2). The whole expressed
      cellular mRNAs were systematically analyzed by "DNA microchips" technology to
      identify all individual species quantitatively affected by field exposure.
      Comparisons were made between RNA samples from exposed and control sham-exposed
      cells. Results indicated that immediately and 4 h after exposure there were
      almost no differentially modulated mRNA species. However, samples obtained at 24
      h after exposure showed a small number of limitedly differential signals (7 down
      regulated and 3 up-regulated with a cut-off value of +/-1.5; 38 and 11,
      respectively, with a cut-off value of +/-1.3), which included mostly mRNA
      encoding transcription factors and DNA binding proteins. Nevertheless, in
      identical experimental conditions, we previously demonstrated enzymatic changes
      of alkaline phosphatase occurring immediately after exposure and declining in a
      few hours. Therefore, since enzymatic changes occur before those observed at gene
      regulation level, it is conceivable that only earlier effects are directly due
      the treatment and then these effects are later able to affect gene expression
      only indirectly.

PMID- 23977832
TI  - Two-dimensional fluorescence lifetime correlation spectroscopy. 1. Principle.
AB  - Fluorescence correlation spectroscopy (FCS) is a unique tool for investigating
      microsecond molecular dynamics of complex molecules in equilibrium. However,
      application of FCS in the study of molecular dynamics has been limited, owing to
      the complexity in the extraction of physically meaningful information. In this
      work, we develop a new method that combines FCS and time-correlated single photon
      counting (TCPSC) to extract unambiguous information about equilibrium dynamics of
      complex molecular systems. In this method, which we name two-dimensional
      fluorescence lifetime correlation spectroscopy (2D FLCS), we analyze the
      correlation of the fluorescence photon pairs, referring to the fluorescence
      lifetime. We first obtain the correlations of the photon pairs with respect to
      the excitation-emission delay times in the form of a two-dimensional (2D) map.
      Then, the 2D map is converted to the correlations between different species that
      have distinct fluorescence lifetimes using inverse Laplace transformation. This
      2D FLCS is capable of visualizing the equilibration dynamics of complex molecules
      with microsecond time resolution at the single-molecule level. We performed a
      kinetic Monte Carlo simulation of a TCPSC-FCS experiment as a proof-of-principle
      example. The result clearly shows the validity of the proposed method and its
      high potential in analyzing the photon data of dynamic systems. 

PMID- 23977830
TI  - Redox modulation of endothelial nitric oxide synthase by glutaredoxin-1 through
      reversible oxidative post-translational modification.
AB  - S-Glutathionylation is a redox-regulated modification that uncouples endothelial
      nitric oxide synthase (eNOS), switching its function from nitric oxide (NO)
      synthesis to (*)O2(-) generation, and serves to regulate vascular function. While
      in vitro or in vivo eNOS S-glutathionylation with modification of Cys689 and
      Cys908 of its reductase domain is triggered by high levels of glutathione
      disulfide (GSSG) or oxidative thiyl radical formation, it remains unclear how
      this process may be reversed. Glutaredoxin-1 (Grx1), a cytosolic and glutathione
      dependent enzyme, can reverse protein S-glutathionylation; however, its role in
      regulating eNOS S-glutathionylation remains unknown. We demonstrate that Grx1 in
      the presence of glutathione (GSH) (1 mM) reverses GSSG-mediated eNOS S
      glutathionylation with restoration of NO synthase activity. Because Grx1 also
      catalyzes protein S-glutathionylation with an increased [GSSG]/[GSH] ratio, we
      measured its effect on eNOS S-glutathionylation when the [GSSG]/[GSH] ratio was
      >0.2, which can occur in cells and tissues under oxidative stress, and observed
      an increased level of eNOS S-glutathionylation with a marked decrease in eNOS
      activity without uncoupling. This eNOS S-glutathionylation was reversed with a
      decrease in the [GSSG]/[GSH] ratio to <0.1. Liquid chromatography and tandem mass
      spectrometry identified a new site of eNOS S-glutathionylation by Grx1 at Cys382,
      on the surface of the oxygenase domain, without modification of Cys689 or Cys908,
      each of which is buried within the reductase. Furthermore, Grx1 was demonstrated
      to be a protein partner of eNOS in vitro and in normal endothelial cells,
      supporting its role in eNOS redox regulation. In endothelial cells, Grx1
      inhibition or gene silencing increased the level of eNOS S-glutathionylation and
      decreased the level of cellular NO generation. Thus, Grx1 can exert an important
      role in the redox regulation of eNOS in cells.

PMID- 23977833
TI  - Resveratrol protects against vinorelbine-induced vascular endothelial cell
      injury.
AB  - Vinorebine (VNR), a second-generation vinca alkaloid antitumor drug, caused
      serious local venous toxicities, such as venous irritation, phlebitis and
      necrotizing vasculitis. This study investigated whether resveratrol (RES), a
      naturally occurring polyphenol compound, could reduce the vascular injury induced
      by VNR. Human vascular endothelial cell line ECV-304 cells were exposed to VNR
      for 10 min and then cells were cultured with serum-free medium with or without
      RES for 24 h. MTT (3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphe-nyl-2-tetrazolium
      bromide) assay was used to detect the cell viability. Reactive oxygen species
      (ROS) was measured with 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The
      activity of superoxide dismutase (SOD) was assessed by SOD detection kit. VNR
      decreased the viability of ECV-304 cells in a dose-dependent manner. Moreover,
      VNR caused cell apoptosis, the generation of intracellular ROS and the reduction
      of intracellular SOD. Interestingly, pretreatment with RES for 2 h increased the
      cell viability in a dose-dependent manner. Cell apoptosis, the intracellular ROS
      generation and the reduction of intracellular SOD induced by VNR were also
      attenuated when cells were pretreated with RES for 2 h. These results
      demonstrated that RES would protect against vascular endothelial cell injury
      induced by VNR. So the use of RES together with VNR may be a possible therapeutic
      approach to avoid the vascular injury induced by VNR.

PMID- 23977834
TI  - Risk factors for infection and disease in child contacts of multidrug-resistant
      tuberculosis: a cross-sectional study.
AB  - BACKGROUND: Young children exposed to Mycobacterium tuberculosis have a high risk
      of disease progression following infection. This study aimed to determine risk
      factors for M. tuberculosis infection and disease in children following exposure
      to adults with multidrug-resistant (MDR) tuberculosis (TB). METHODS: Cross
      sectional study; all children aged < 5 years, routinely referred per local
      guidelines to the provincial specialist MDR-TB clinic, Western Cape Province,
      South Africa, following identification as contacts of adult MDR-TB source cases,
      were eligible for enrolment from May 2010 through April 2011. Demographic,
      clinical and social characteristics were collected. All children underwent HIV
      and tuberculin skin testing. RESULTS: Of 228 children enrolled (median age: 30
      months), 102 (44.7%) were classified as infected. Of these, 15 (14.7%) had TB
      disease at enrolment. Of 217 children tested for HIV, 8 (3.7%) were positive. In
      adjusted analysis, child's age (AOR: 1.43; 95% CI: 1.13-1.91; p = 0.002) and
      previous TB treatment history (AOR: 2.51; 95% CI: 1.22-5.17; p = 0.01) were
      independent risk factors for infection. Increasing age of the MDR-TB source case
      (AOR: 0.67; 95% CI: 0.45-1.00; p = 0.05) was protective and source case alcohol
      use (AOR: 2.59; 95% CI: 1.29-5.22; p = 0.007) was associated with increased odds
      of infection in adjusted analysis. Decreasing age of the child (p = 0.01) and
      positive HIV status (AOR: 25.3; 95% CI: 1.63-393; p = 0.01) were associated with
      prevalent TB disease. CONCLUSION: A high proportion of children exposed to MDR-TB
      are infected or diseased. Early contact tracing might provide opportunities to
      prevent the progression to TB disease in children identified as having been
      exposed to MDR-TB.

PMID- 23977835
TI  - Differentiating homogeneous and heterogeneous water oxidation catalysis:
      confirmation that [Co4(H2O)2(alpha-PW9O34)2]10- is a molecular water oxidation
      catalyst.
AB  - Distinguishing between homogeneous and heterogeneous catalysis is not
      straightforward. In the case of the water oxidation catalyst (WOC)
      [Co4(H2O)2(PW9O34)2](10-) (Co4POM), initial reports of an efficient, molecular
      catalyst have been challenged by studies suggesting that formation of cobalt
      oxide (CoOx) or other byproducts are responsible for the catalytic activity.
      Thus, we describe a series of experiments for thorough examination of active
      species under catalytic conditions and apply them to Co4POM. These provide strong
      evidence that under the conditions initially reported for water oxidation using
      Co4POM (Yin et al. Science, 2010, 328, 342), this POM anion functions as a
      molecular catalyst, not a precursor for CoOx. Specifically, we quantify the
      amount of Co(2+)(aq) released from Co4POM by two methods (cathodic adsorptive
      stripping voltammetry and inductively coupled plasma mass spectrometry) and show
      that this amount of cobalt, whatever speciation state it may exist in, cannot
      account for the observed water oxidation. We document that catalytic O2 evolution
      by Co4POM, Co(2+)(aq), and CoOx have different dependences on buffers, pH, and
      WOC concentration. Extraction of Co4POM, but not Co(2+)(aq) or CoOx into toluene
      from water, and other experiments further confirm that Co4POM is the dominant
      WOC. Recent studies showing that Co4POM decomposes to a CoOx WOC under
      electrochemical bias (Stracke and Finke, J. Am. Chem. Soc., 2011, 133, 14872), or
      displays an increased ability to reduce [Ru(bpy)3](3+) upon aging (Scandola, et
      al., Chem. Commun., 2012, 48, 8808) help complete the picture of Co4POM behavior
      under various conditions but do not affect our central conclusions. 

PMID- 23977836
TI  - Clostridium difficile infection caused by binary toxin-positive strains.

PMID- 23977837
TI  - Integrated lab-in-syringe platform incorporating a membraneless gas-liquid
      separator for automatic cold vapor atomic absorption spectrometry.
AB  - This manuscript reports the proof-of-concept of a novel integrated lab-in
      syringe/gas-liquid separation (LIS/GLS) batch-flow system based on a programmable
      flow for automatic cold vapor atomic absorption spectrometric assays. Homogeneous
      mixing of metered volumes of sample and reagent solutions drawn up in a sandwich
      type mode along with in situ vapor generation are accomplished inside the
      microsyringe in a closed manner, while the separation of vapor species is
      achieved via the membraneless GLS located at the top of the syringe's valve in
      the upright position. The potentials of the proposed manifold were demonstrated
      for trace inorganic mercury determination in drinking waters and seawater. For a
      3.0 mL sample, the limit of detection and repeatability (RSD) were found to be
      0.03 MUg L(-1) Hg(II) and 3.1% (at the 2.0 MUg L(-1) concentration level),
      respectively, with a dynamic range extending up to 10.0 MUg L(-1). The proposed
      system fulfills the requirements of US-EPA, WHO, and EU Council Directives for
      measurements of the maximum allowed concentrations of inorganic mercury in
      drinking water. 

PMID- 23977838
TI  - Molecular crosstalk between apoptosis and autophagy induced by a novel 2
      methoxyestradiol analogue in cervical adenocarcinoma cells.
AB  - BACKGROUND: 2-Methoxyestradiol has been shown to induce both autophagy and
      apoptosis in various carcinogenic cell lines. Although a promising anti-cancer
      agent, it has poor bioavailability and rapid in vivo metabolism which decreases
      its efficiency. In order to improve 2-methoxyestradiol's anti-proliferative
      properties, a novel 2-methoxyestradiol analogue, 2-ethyl-3-O-sulphamoyl-estra
      1,3,5 (10)16-tetraene (ESE-16), was previously in silico-designed in our
      laboratory. This study investigated ESE-16 for its anti-proliferative potential
      on a cervical adenocarcinoma cell (HeLa) cell line. Additionally, the possible
      intracellular crosstalk mechanisms between the two types of cell death were
      investigated. METHODS AND RESULTS: HeLa cells exposed to 0.5 MUM ESE-16 for 24
      hours showed morphological evidence of both apoptotic and autophagic death
      pathways as assessed by polarization-optical transmitted light differential
      interference contrast microscopy, fluorescent microscopy and transmission
      electron microscopy. Flow cytometric cyclin B1 quantification revealed induction
      of programmed cell death after halting cell cycle progression in metaphase.
      Confocal microscopy demonstrated that ESE-16 caused microtubule fragmentation.
      Flow cytometric analysis of cell cycle progression and phosphatidylserine flip
      determination confirmed induction of apoptosis. Moreover, an increase in
      aggresome formation and microtubule-associated protein light chain, LC3, was
      demonstrated indicative of autophagy. Both caspase 8 and 3 were upregulated in a
      spectrophotometric analysis, indicating the involvement of the extrinsic pathway
      of apoptotic induction. CONCLUSIONS: We conclude that the novel in silico
      designed compound, ESE-16, exerts its anti-proliferative effect on the
      tumorigenic human epithelial cervical (HeLa) cells by sequentially targeting
      microtubule integrity, resulting in a metaphase block, causing induction of both
      autophagic and apoptotic cell death via a crosstalk mechanism that involves the
      extrinsic pathway. Future investigations will expand on signal transduction
      pathways involved in both apoptosis and autophagy for assessment of ESE-16
      effects on microtubule dynamic instability parameters.

PMID- 23977839
TI  - Radical cations of aromatic selenium compounds: role of Se...X nonbonding
      interactions.
AB  - Selenium centered radical cations in aliphatic selenium compounds are stabilized
      by formation of two-center-three electron (2c-3e) hemi bonds either with nearby
      heteroatoms forming monomer radicals or with selenium atoms of the parent
      molecules forming dimer radicals. Such radicals in aromatic selenium compounds
      would generally be stabilized as monomers by the delocalization of the spin
      density along the aromatic ring. To test the assumption if aromatic selenides
      having Se...X nonbonding interactions can show different types of radical
      cations, we have performed pulse radiolysis studies of three structurally related
      aromatic selenium compounds and the results have been substantiated with cyclic
      voltammetry and quantum chemical calculations. The three aromatic selenium
      compounds have functional groups like -CH2N(CH3)2 (1), -CH2OH (2), and -CH3 (3)
      at ortho position to the -SeCH3 moiety. The energy of Se...X nonbonding
      interactions (E(nb)) for these compounds is in the order 1 (Se...N) > 2 (Se...O)
      > 3 (Se...H). Radical cations, 1(*+), 2(*+) and 3(*+) were produced by the one
      electron oxidation of 1, 2 and 3 by radiolytically generated (*)OH and Br2(*-)
      radicals. Results on transient spectra, lifetime, and secondary reactions of
      1(*+), 2(*+), and 3(*+) indicated that 1(*+) shows a significantly different
      absorption spectrum, longer lifetime, and less oxidizing power compared to those
      of 2(*+) or 3(*+). Quantum chemical calculations suggested that 1(*+) is
      stabilized by the formation of a 2c-3e bond between Se and N atoms, whereas 2(*+)
      and 3(*+) acquire stability through the delocalization of the spin density on the
      aromatic ring. These results provide evidence for the first time that stronger
      nonbonding interactions between Se...N in the ground state, facilitate the
      formation of stabilized radical cations, which can significantly influence the
      redox chemistry and the biological activity of aromatic selenium compounds.

PMID- 23977840
TI  - MP29-02: a breakthrough for the treatment of allergic rhinitis.
AB  - INTRODUCTION: Allergic rhinitis (AR) can be challenging to treat. For many
      patients, current therapies (including multiple therapies) provide insufficient
      symptom relief. There is, therefore, a clear unmet medical need for a new and
      more effective AR treatment option. MP29-02 ( Dymista ) is a novel intranasal
      formulation of azelastine hydrochloride and fluticasone propionate in an advanced
      delivery system. AREAS COVERED: The goal of this article is to review all MP29-02
      clinical data currently published with a view to establish its potential to fill
      the current unmet medical need in AR. Relevant articles and abstracts were
      reviewed from PUBMED and conference proceedings. EXPERT OPINION: MP29-02
      represents a breakthrough in AR management for the following reasons: i) MP29-02
      has been extensively studied in comparison to first-line therapies in both
      seasonal AR (SAR) patients and in those with chronic rhinitis (i.e., perennial
      allergic rhinitis [PAR] and nonallergic (vasomotor) rhinitis) in one of the
      largest direct head-to-head clinical trial programmes in AR, to date. ii) With
      MP29-02, the efficacy of an intranasal corticosteroid (INS), the first-line
      choice for AR has been exceeded for the first time without safety repercussions.
      AR patients treated with MP29-02 experience significantly greater relief from
      their overall nasal and ocular symptoms compared to two first-line AR therapies,
      irrespective of season, symptom type, or disease severity. More patients treated
      with MP29-02 achieve a substantial reduction (i.e., 50% reduction) in their
      symptoms and also complete symptom relief and achieve these clinically relevant
      responses days faster than an INS or antihistamine. iii) Formulation of a topical
      medication is critical, and MP29-02's novel formulation and/or its device
      contribute to its clinical efficacy.

PMID- 23977841
TI  - Removal of alachlor from water by catalyzed ozonation on Cu/Al2O3 honeycomb.
AB  - BACKGROUND: The herbicide alachlor (2-chloro-2'6'-diethyl-N
      methoxymethylacetanilide) has been known as a probable human carcinogen, and the
      MCL (minimum contamination level) for drinking water has been set at 2 MUg L-1.
      Therefore, the advanced methods for effectively removing it from water are a
      matter of interest. Catalyzed ozonation is a promising method for refractory
      organics degradation. Cu/Al2O3 catalyzed ozonation for degrading an endocrine
      disruptor (alachlor) in water was investigated. RESULTS: Experimental results
      showed that the ozonation of alachlor can be effectively catalyzed and enhanced
      by Cu/Al2O3-honeycomb. The main intermediate products formed (aliphatic
      carboxylic acids) were mineralized to a large extent in the catalytic process.
      CONCLUSIONS: This study has shown that Cu/Al2O3-honeycomb is a feasible and
      efficient catalyst in the ozonation of alachlor in water. Less intermediate
      oxidation product was produced in the catalytic process than in the uncatalytic
      one. Furthermore, the mineralization of alachlor could be enhanced by increasing
      the pH of the reaction solution.

PMID- 23977842
TI  - The dog as a model for peri-implantitis: A review.
AB  - OBJECTIVE: To analyze the current available experimental canine models for peri
      implantitis. MATERIAL AND METHODS: Electronic databases of the PubMed, EBSCOhost,
      and Cochrane Library were searched for dog studies on peri-implantitis induction
      methodology, until October 31, 2012. The eligibility of the studies for this
      review was based on the screening of two independent reviewers. RESULTS: After
      screening, 50 publications were eligible for review. The most used animal model
      was the Beagle (n = 23). The bilateral mandible four premolar were the most
      extracted group of teeth (n = 20) and the majority of the studies had the
      placement of six implants in the jaw with only five (n = 5) of them reporting on
      interimplant distance. All publications reported peri-implantitis induction using
      ligature during a variable period of time and with a subsequent heterogeneous
      loss of peri-implant bone. The ligature placement and maintenance around the
      implant varied greatly between the publications. The constant use of ligatures,
      sometimes traumatically forced to the peri-implant sulcus, may influence the
      degree of bone loss during canine experimental peri-implantitis overlapping the
      contribution of implant surface to the onset and development of this pathology.
      CONCLUSIONS: A great heterogeneity exists among the studies reporting on the
      induction of peri-implantitis in canine. Experimental peri-implantitis model has
      suffered a change through the last years, from an exclusive ligature-induced to a
      ligature-induced and nonligature induced progression, thus approaching the
      natural occurrence of this pathology. The ideal canine peri-implantitis induction
      model would be a naturally occurring peri-implanititis induction without the
      action of any ligature.

PMID- 23977843
TI  - Three new mixed-alkali- and alkaline-earth-metal borates: from 1D chain to 2D
      layer to 3D framework.
AB  - Three new mixed-metal borates, K4Ba2[B14O20(OH)10].3H2O (1), LiSr2[B10O16(OH)3]
      (2), and LiBa[B9O15] (3), have been made under hydro(solvo)thermal conditions and
      characterized by means of IR, UV-vis-near-IR, thermogravimetric analysis, powder
      X-ray diffraction, and single-crystal X-ray diffraction, respectively. 1 is a 1D
      chain constructed from B14O21(OH)10(10-) cluster units, 2 is of a 2D layer with
      nine-membered-ring windows built up of B10O19(OH)3(9-) cluster units, while 3
      exhibits a 3D framework with 12-membered-ring channels composed of B3O7 cluster
      units. 

PMID- 23977844
TI  - Targeted quantitative proteomics for the analysis of 14 UGT1As and -2Bs in human
      liver using NanoUPLC-MS/MS with selected reaction monitoring.
AB  - Targeted quantitative proteomics using heavy isotope dilution techniques is
      increasingly being utilized to quantify proteins, including UGT enzymes, in
      biological matrices. Here we present a multiplexed method using nanoLC-MS/MS and
      multiple reaction monitoring (MRM) to quantify 14 UGT1As and UGT2Bs in liver
      matrices. Where feasible, we employ two or more proteotypic peptides per protein,
      with only four proteins quantified with only one proteotypic peptide. We apply
      the method to analysis of a library of 60 human liver microsome (HLM) and
      matching S9 samples. Ten of the UGT isoforms could be detected in liver, and the
      expression of each was consistent with mRNA expression reported in the
      literature. UGT2B17 was unusual in that ~30% of liver microsomes had no or little
      (<0.5 pmol/mg protein) content, consistent with a known common polymorphism.
      Liver S9 UGT concentrations were approximately 10-15% those of microsomes. The
      method was robust, precise, and reproducible and provides novel UGT expression
      data in human liver that will benefit rational approaches to evaluate metabolism
      in drug development. 

PMID- 23977845
TI  - Three-dimensional nanostructured bilayer solid oxide fuel cell with 1.3 W/cm(2)
      at 450  degrees C.
AB  - Obtaining high power density at low operating temperatures has been an ongoing
      challenge in solid oxide fuel cells (SOFC), which are efficient engines to
      generate electrical energy from fuels. Here we report successful demonstration of
      a thin-film three-dimensional (3-D) SOFC architecture achieving a peak power
      density of 1.3 W/cm(2) obtained at 450  degrees C. This is made possible by
      nanostructuring of the ultrathin (60 nm) electrolyte interposed with a
      nanogranular catalytic interlayer at the cathode/electrolyte interface. We
      attribute the superior cell performance to significant reduction in both the
      ohmic and the polarization losses due to the combined effects of employing an
      ultrathin film electrolyte, enhancement of effective area by 3-D architecture,
      and superior catalytic activity by the ceria-based interlayer at the cathode.
      These insights will help design high-efficiency SOFCs that operate at low
      temperatures with power densities that are of practical significance. 

PMID- 23977846
TI  - Effects of carbon coating and pore corrugation on capillary condensation of
      nitrogen in SBA-15 mesoporous silica.
AB  - To examine the origin of an ink-bottle-like structure in SBA-15 formed by carbon
      coating and the effects of pore corrugation on capillary condensation and
      evaporation of a vapor in the cylindrical pores, we measured the adsorption
      isotherms of nitrogen at 77 K on 10 kinds of SBA-15 samples before and after a
      carbon coating process by the exposure to acetylene at 1073 K, as well as
      desorption scanning curves and subloops on the untreated samples. These SBA-15
      samples were synthesized under the different conditions of initial SiO2/P123
      ratio and hydrothermal treatment. SBA-15 with relatively large microporosity
      tends to form easily constrictions inside the main channels by the carbon
      coating. This strongly suggests that the rough pore walls of SBA-15 may induce
      the incomplete wetting of carbon layers on the pore walls to form the
      constrictions inside the cylindrical pores. A comparison of two subloops implies
      that the pores of SBA-15 synthesized with a SiO2/P123 ratio of 75 consist of an
      assembly of connecting domains of different diameters; that is, the pores are
      highly corrugated. For SBA-15 synthesized with a SiO2/P123 ratio of 60, the
      amplitude of the pore corrugation is significantly decreased by the prolonged
      hydrothermal treatment at 373 K. On the other hand, for SBA-15 synthesized with a
      SiO2/P123 ratio of 45, the amplitude of the corrugation is negligibly small,
      although the cylindrical pores are interconnected through narrow necks with each
      other. It is found that the smaller the amplitude of the pore corrugation, the
      smaller the width of the hysteresis loop. 

PMID- 23977847
TI  - Microtomographic analysis of lower urinary tract obstruction.
AB  - Prenatal obstruction of the lower urinary tract may result in megacystis, with
      subsequent development of hydroureter, hydronephrosis, and renal damage. Oligo-
      or anhydramnios, pulmonary hypoplasia, and prune belly syndrome are lethal
      consequences. Causes and mechanisms responsible for obstruction remain unclear
      but might be clarified by anatomic study at autopsy. To this end, we employed 2
      methods of tomographic imaging-optical projection tomography and contrast
      enhanced microCT scanning-to elucidate the anatomy of the intact urinary bladder
      and urethra in 10 male fetuses with lower urinary tract obstruction. Images were
      compared with those from 9 age-matched controls. Three-dimensional images,
      rotated and sectioned digitally in multiple planes, permitted thorough
      examination while preserving specimens for later study. Both external and
      internal features of the bladder and urethra were demonstrated; small structures
      (ie, urethral crest, verumontanum, prostatic utricle, ejaculatory ducts) were
      seen in detail. Types of obstruction consisted of urethral atresia (n  =  5),
      severe urethral stenosis (n  =  2), urethral diaphragm (n  =  2), or physical
      kinking (n  =  1); classic (Young type I) posterior urethral valves were not
      encountered. Traditional light microscopy was then used to verify tomographic
      findings. The prostate gland was hypoplastic or absent in all cases; in 1,
      prostatic tissue was displaced inferior to the verumontanum. Findings support
      previous views that dissection may produce valve-like artifacts (eg, bisection of
      an obstructing diaphragm) and that deformation of an otherwise normal urethra may
      result in megacystis. The designation "posterior urethral valves" should not be
      used as a generic expression of urethral obstruction unless actual valves are
      demonstrated.

PMID- 23977848
TI  - An inhibitor of NADPH oxidase-4 attenuates established pulmonary fibrosis in a
      rodent disease model.
AB  - Idiopathic pulmonary fibrosis is a chronic progressive disease of increasing
      prevalence for which there is no effective therapy. Increased oxidative stress
      associated with an oxidant-antioxidant imbalance is thought to contribute to
      disease progression. NADPH oxidases (Nox) are a primary source of reactive oxygen
      species within the lung and cardiovascular system. We demonstrate that the Nox4
      isoform is up-regulated in the lungs of patients with IPF and in a rodent model
      of bleomycin-induced pulmonary fibrosis and vascular remodeling. Nox4 is
      constitutively active, and therefore increased expression levels are likely to
      contribute to disease pathology. Using a small molecule Nox4/Nox1 inhibitor, we
      demonstrate that targeting Nox4 results in attenuation of an established fibrotic
      response, with reductions in gene transcripts for the extracellular matrix
      components collagen 1alpha1, collagen 3alpha1, and fibronectin and in principle
      pathway components associated with pulmonary fibrosis and hypoxia-mediated
      vascular remodeling: transforming growth factor (TGF)-beta1, plasminogen
      activator inhibitor-1, hypoxia-inducible factor, and Nox4. TGF-beta1 is a
      principle fibrotic mediator responsible for inducing up-regulation of profibrotic
      pathways associated with disease pathology. Using normal human lung-derived
      primary fibroblasts, we demonstrate that inhibition of Nox4 activity using a
      small molecule antagonist attenuates TGF-beta1-mediated up-regulation in
      expression of profibrotic genes and inhibits the differentiation of fibroblast to
      myofibroblasts, that is associated with up-regulation in smooth muscle actin and
      acquisition of a contractile phenotype. These studies support the view that
      targeting Nox4 may provide a therapeutic approach for attenuating pulmonary
      fibrosis. 

PMID- 23977863
TI  - Streptococcus suis meningitis and bacteremia in man, French Guiana.

PMID- 23977864
TI  - Effects of exercise with or without blueberries in the diet on cardio-metabolic
      risk factors: an exploratory pilot study in healthy subjects.
AB  - BACKGROUND: The improvement of insulin sensitivity by exercise has been shown to
      be inhibited by supplementation of vitamins acting as antioxidants. OBJECTIVE: To
      examine effects of exercise with or without blueberries, containing natural
      antioxidants, on cardio-metabolic risk factors. METHODS: Fifteen healthy men and
      17 women, 27.6 +/- 6.5 years old, were recruited, and 26 completed a randomized
      cross-over trial with 4 weeks of exercise by running/jogging 5 km five times/week
      and 4 weeks of minimal physical activity. Participants were also randomized to
      consume 150 g of blueberries, or not, on exercise days. Laboratory variables were
      measured before and after a 5 km running-race at maximal speed at the beginning
      and end of each period, i.e. there were four maximal running-races and eight
      samplings in total for each participant. RESULTS: Insulin and triglyceride levels
      were reduced while HDL-cholesterol increased by exercise compared with minimal
      physical activity. Participants randomized to consume blueberries showed an
      increase in fasting glucose levels compared with controls, during the exercise
      period (blueberries: from 5.12 +/- 0.49 mmol/l to 5.32 +/- 0.29 mmol/l; controls:
      from 5.24 +/- 0.27 mmol/l to 5.17 +/- 0.23 mmol/l, P = 0.04 for difference in
      change). Triglyceride levels fell in the control group (from 1.1 +/- 0.49 mmol/l
      to 0.93 +/- 0.31 mmol/l, P = 0.02), while HDL-cholesterol increased in the
      blueberry group (from 1.51 +/- 0.29 mmol/l to 1.64 +/- 0.33 mmol/l, P = 0.006).
      CONCLUSIONS: Ingestion of blueberries induced differential effects on cardio
      metabolic risk factors, including increased levels of both fasting glucose and
      HDL-cholesterol. However, since it is possible that indirect effects on food
      intake were induced, other than consumption of blueberries, further studies are
      needed to confirm the findings.

PMID- 23977865
TI  - Palpable maculopapular rash with elevated ESR: what is your diagnosis?

PMID- 23977868
TI  - High-sensitivity cardiac troponins: no more 'negatives'.
AB  - According to recently published expert guidelines, cardiac troponins are the only
      accepted biomarkers to define acute myocardial infarction. New high sensitivity
      cardiac troponin assays provide exciting opportunities for early rule-out and
      rule-in strategies and for identifying high-risk patients early in their
      presentation to guide early treatment and intervention. This review briefly
      discusses the history of troponin testing, before going on to cover clinical uses
      of the new highly sensitive assays in the early assessment of acute myocardial
      infection. Common clinical pitfalls with the use of these assays are discussed,
      as is the use of highly sensitive troponins more widely as prognostic markers.
      Likely future developments in this area are discussed. 

PMID- 23977866
TI  - Functional stimulation of graft nerves has minor effects on insulin release from
      transplanted rat pancreatic islets.
AB  - INTRODUCTION: Morphological evidence for reinnervation of pancreatic islet grafts
      is plentiful. However, to what extent intra-graft nerves influence the endocrine
      functions of the islet transplant is largely unknown. We therefore aimed to
      directly stimulate nerves leading to islet grafts with electrodes and measure
      insulin secretion in response to this. METHODS: We implanted syngeneic islets
      under the renal capsule of rats, and examined them 1 or 7-9 months later. In
      anesthetized rats blood samples were collected from the renal vein and femoral
      artery, respectively, during electrode stimulation of the nerves leading to the
      islet grafts. RESULTS: As expected, nerve stimulation decreased renal blood flow.
      However, serum insulin concentrations in samples derived from the renal vein or
      femoral artery changed in concert with one another, both during normoglycemia and
      acute hyperglycemia. CONCLUSION: Reinnervation which occurs after islet
      transplantation under the renal capsule has minor effects on graft endocrine
      function.

PMID- 23977867
TI  - Brain death due to fat embolism - could moderate hypercapnia and prone position
      be blamed for the tonsillar herniation?
AB  - Fat embolism to the systemic circulation in polytrauma patients is very common.
      The fat embolism syndrome (FES), however, is a rare condition. We describe a case
      of traumatic femur fracture with FES that was presented as acute tonsillar
      herniation (coning) and brain death postoperatively. We believe that in this case
      the prone position and moderate hypercapnia contributed to the acute coning.

PMID- 23977869
TI  - Intrathecal baclofen therapy in children with severe spasticity: Outcome and
      complications.
AB  - OBJECTIVE: To investigate clinical efficacy and incidence of complications
      regarding intrathecal baclofen (ITB) therapy in children. METHODS: Retrospective
      medical chart review of 15 paediatric patients with congenital brain injuries who
      underwent ITB implantation for treatment of severe spasticity between 2003 and
      2009. RESULTS: Compared to the preoperative state, ITB therapy significantly
      reduced spasticity of lower limbs with corresponding decrease of the modified
      Ashworth scale (p < 0.05), while baclofen dosage increased (p = 0.001). Cobb
      angle of patients with scoliosis prior to ITB therapy (n = 8) increased
      significantly (p < 0.05) during follow-up. Overall, 10 complications (nine device
      related and one accidental) were found in six patients (40%), mostly emerging
      within the first three years after implantation. CONCLUSION: Intrathecal baclofen
      is an effective therapy option for paediatric patients to significantly reduce
      spasticity of lower limbs. The high incidence of complications implicates the
      need for a close monitoring of the patients especially in the early post
      operative period.

PMID- 23977870
TI  - Validation of the Turkish version of "Test for Respiratory and Asthma Control in
      Kids (TRACK)" questionnaire.
AB  - BACKGROUND: Test for Respiratory and Asthma Control in Kids (TRACK) questionnaire
      is the first to measure both the risk and impairment domains of the current
      guidelines in preschool children. We aimed to measure the reliability, validity
      and responsiveness of the Turkish version of the TRACK. METHODS: A total of 268
      children (69.8% boys) were included in the study. Caregivers responded to three
      individual TRACK questionnaires, at each clinical visit (baseline, 1st month, and
      3rd month). At each visit, physicians determined the control level and the
      treatment strategy based on the GINA guideline recommendations. RESULTS: The
      internal consistency reliability of the Turkish version of the TRACK
      questionnaire was found to be 0.74, 0.74, and 0.76 at each of the three visits,
      respectively (reliability statistics, Cronbach's alpha). There was a significant
      difference between the mean TRACK scores of the patients in different asthma
      control status categories (p < 0.001). The test-retest reliability in stable
      patients was 0.90. The optimal cut-off scores according to the Youden index were
      80 and 60 points for uncontrolled and very poorly controlled children,
      respectively. CONCLUSION: The Turkish version of the TRACK is an accurate and
      reliable tool for evaluating asthma control status among preschool Turkish
      children. Its widespread use may help physicians correctly assess control levels
      among children and may improve the quality of life for both patients and their
      caregivers.

PMID- 23977871
TI  - Poly(dodecyl methacrylate) as solvent of paraffins for phase change materials and
      thermally reversible light scattering films.
AB  - Paraffins are typical organic phase change materials (PCM) used for latent heat
      storage. For practical applications they must be encapsulated to prevent leakage
      or agglomeration during fusion. In this study it is shown that eicosane (C20H42 =
      C20) in the melted state could be dissolved in the hydrophobic domains of
      poly(dodecyl methacrylate) (PDMA) up to concentrations of 30 wt %, avoiding the
      need of encapsulation. For a 30 wt % solution, the heat of phase change was close
      to 69 J/g, a reasonable value for its use as a PCM. The fully converted solution
      remained transparent at 80  degrees C with no evidence of phase separation but
      became opaque by cooling as a consequence of paraffin crystallization. Heating
      above the melting temperature regenerated a transparent material. A high contrast
      ratio and abrupt transition between opaque and transparent states was observed
      for the 30 wt % blends, with a transparent state at 35  degrees C and an opaque
      state at 23  degrees C. This behavior was completely reproducible during
      consecutive heating/cooling cycles, indicating the possible use of this material
      as a thermally reversible light scattering (TRLS) film. 

PMID- 23977872
TI  - Changes over swim lessons in parents' perceptions of children's supervision needs
      in drowning risk situations: "His swimming has improved so now he can keep
      himself safe".
AB  - OBJECTIVE: The aim of this longitudinal study was to determine how children's
      participation in swim lessons impacts parents' appraisals of children's drowning
      risk and need for supervision. METHOD: Parents with 2-5-year old children
      enrolled in community swim lessons completed the same survey measures up to 4
      times over an 8-month period. RESULTS: Multilevel regression analyses examining
      temporal relationships between parents' perceptions of their child's swim
      ability, supervision needs around water, and children's ability to keep
      themselves safe in drowning risk situations revealed that as children progressed
      through swim lessons, parents' perceptions of their child's swim ability and
      their belief that children are capable of keeping themselves safe around water
      increased. Further, the relation between parents' perceptions of swim ability and
      judgments of children's supervision needs was mediated through parents' judgment
      about their child's ability to secure their own safety near water. CONCLUSIONS:
      As parents perceive their child to be accumulating swim skills, they increasingly
      believe that children are capable of keeping themselves from drowning, and as a
      result, that less active parent supervision of their child is necessary.
      Implications of these findings for intervention efforts to counter this unwelcome
      way of thinking that may arise through continued participation in swim lessons
      are discussed. Incorporating a parent-focused component into children's learn-to
      swim programs to promote more realistic appraisals of children's supervision
      needs and drowning risks may further enhance the positive benefits that swim
      lessons have for children's safety.

PMID- 23977873
TI  - The course of binge eating from adolescence to young adulthood.
AB  - OBJECTIVE: The course of binge eating in adolescence is variable, and little is
      known about factors maintaining binge eating behaviors. The current study sought
      to characterize the course of binge eating and identify psychosocial factors
      associated with its maintenance. METHOD: A population-based sample reported on
      binge eating, depression symptoms, self-esteem, and body satisfaction at 5-year
      intervals spanning early/middle adolescence (Time 1 [T1]), late adolescence/early
      young adulthood (Time 2 [T2]), and early/middle young adulthood (Time 3 [T3]).
      Logistic regression examined factors predicting maintenance or cessation of binge
      eating. RESULTS: A total of 15.8% of participants with binge eating at T1
      continued to report binge eating at T2, and 42.0% of participants with binge
      eating at T2 continued to report binge eating at T3. From T1 to T2, improvements
      in self-esteem predicted cessation of binge eating. From T2 to T3, cessation of
      binge eating was predicted by improved body satisfaction, greater decreases in
      depression symptoms, and greater improvements in self-esteem. CONCLUSIONS: Binge
      eating is relatively stable from late adolescence/early young adulthood to
      early/middle young adulthood, but less so from middle/late adolescence to late
      adolescence/early young adulthood. Improvements in psychosocial functioning
      during this timeframe may improve the outcome of binge eating, although
      mechanisms responsible for psychosocial changes (e.g., treatment involvement)
      require further investigation. Self-esteem appears to be a particularly salient
      factor involved in binge eating cessation and should be targeted in prevention
      and treatment programs.

PMID- 23977874
TI  - Positive parenting mitigates the effects of poor self-regulation on body mass
      index trajectories from ages 4-15 years.
AB  - OBJECTIVE: This study sought to determine whether parenting style moderates the
      effects of delay of gratification on body mass index (BMI) trajectories from ages
      4-15 years. METHOD: Longitudinal data were analyzed for 778 children drawn from
      the Study of Early Child Care and Youth Development. Parenting style (i.e.,
      authoritative, authoritarian, permissive, and neglectful) was created from
      measures of mothers' sensitivity and expectations for self-control when children
      were age 4 years. Self-regulation was also measured at 4 years using a well-known
      delay of gratification protocol. BMI was calculated from measured height and
      weight at each time point. Mixed modeling was used to test the interaction of
      parenting styles and ability to delay gratification on BMI trajectories from 4-15
      years. RESULTS: There was a significant interaction effect of parenting and
      ability to delay on BMI growth from 4-15 years for boys. Boys who had
      authoritarian mothers and failed to delay gratification had a significantly
      steeper rate of growth in BMI from childhood through adolescence than children in
      any other parenting by delay group. CONCLUSION: Authoritative and permissive
      parenting styles were protective against more rapid BMI gains for boys who could
      not delay gratification. Ability to delay gratification was protective against
      BMI gains for boys who had parents with authoritarian or neglectful parenting
      styles.

PMID- 23977875
TI  - Longitudinal changes in clusters of cancer patients over an 18-month period.
AB  - OBJECTIVE: Cross-sectional studies in cancer have revealed the presence of
      clusters of symptoms (e.g., gastrointestinal, emotional) and of patients (e.g.,
      low or high levels of symptoms), but not much is known about their longitudinal
      evolution. In addition, their relationships with medical factors (e.g., cancer
      sites, treatments) and possible consequences (e.g., functioning) have yet to be
      established. This prospective study assessed the presence of clusters of patients
      in 828 participants scheduled to undergo surgery for cancer. METHODS: The
      patients completed the Hospital Anxiety and Depression Scale, the Insomnia
      Severity Index, the Multidimensional Fatigue Inventory, the EORTC Quality-of-Life
      Questionnaire-C30, and a physical symptoms questionnaire at baseline and 2, 6,
      10, 14, and 18 months later. RESULTS: Cluster analyses identified between five
      and eight clusters of patients depending on the time point. The "Low Symptoms"
      cluster was the most common (24.8 to 35.0% of the sample), whereas one with
      predominant nausea and vomiting symptoms was among the least common (1.6 to
      3.5%). Significant differences were found between cancer sites, treatment
      regimens, quality of life, and functioning scores. Prostate cancer patients and
      those treated by surgery only were overrepresented in the "Low" cluster, whereas
      breast cancer patients were more likely to fall into the "Moderate - Night
      Sweats" cluster. Clusters with more severe psychological symptoms were associated
      with lower functioning and quality of life. CONCLUSIONS: This study revealed
      distinct clusters of patients that varied in number during cancer treatments.
      Findings also identified some clusters associated with lower quality of life and
      functioning, which should receive more clinical attention.

PMID- 23977877
TI  - Comparing theory-based condom interventions: health belief model versus theory of
      planned behavior.
AB  - OBJECTIVE: This study sought to experimentally manipulate the core constructs of
      the Health Belief Model (HBM) and the Theory of Planned Behavior (TPB) in order
      to compare the success of interventions to increase preparatory condom use
      behavior (i.e., purchasing condoms, talking to a boyfriend or girlfriend about
      using condoms, and carrying condoms) based on these theories. METHOD: A total of
      258 participants were randomly assigned to one of three computer-based
      interventions (HBM, TPB, or information-only control). A total of 204 (79.1%)
      completed follow-up assessments 1 month later. RESULTS: Regression analyses were
      conducted to determine which set of theoretical constructs accounted for the most
      variance in behavior at baseline. A series of structural equation models were
      estimated to determine which constructs were the "active ingredients" of change.
      The TPB accounted for 32.8% of the variance in risky sexual behavior at baseline,
      while the HBM only explained 1.6% of the variance. Mediational analyses revealed
      differential intervention effects on perceived susceptibility, perceived
      benefits, and attitudes toward condom use. However, it was attitudes toward
      condom use and condom use self-efficacy that were associated with intentions,
      which then predicted preparatory condom use behavior at follow-up. CONCLUSION:
      Except for attitudes, the mediators that were successfully manipulated by the
      interventions (i.e., perceived susceptibility, perceived severity, and attitudes)
      were not the same constructs that predicted intentions (i.e., attitudes and
      condom use self-efficacy), and subsequently predicted behavior. This suggests
      that the constructs that explain behavior are not the same as those that produce
      behavior change.

PMID- 23977876
TI  - Cognitive influences on sexual risk and risk appraisals in men who have sex with
      men.
AB  - Men who have sex with men (MSM) account for more than half of new HIV infections
      each year. Previous research has linked cognitive variables from the Information,
      Motivational and Behavioral Skills (IMB) Model to sexual risk behavior, but
      cognitions may additionally influence risk appraisals of sexual encounters and
      subsequently potentiate sexual risk. The aim of this study was to use prospective
      event-level data to examine the direct influence of cognitive variables on sexual
      risk in MSM, as well as the moderating effects of these variables on the
      association between unprotected anal intercourse (UAI) and risk appraisals of
      these encounters. One hundred forty-three ethnically diverse MSM were enrolled in
      a 3-month online diary study of sexual behavior. Each week participants reported
      on specific sexual behaviors that occurred during each of up to three sexual
      encounters, including type of sexual behavior, condom use, and perceived risk for
      acquiring HIV during the encounter. All analyses were conducted with Hierarchical
      Linear Modeling. Condom use self-efficacy was the only cognitive variable that
      was directly associated with UAI. However, both HIV knowledge and social norms of
      condom use contributed to accuracy of risk appraisals. Conversely, MSM who were
      highly motivated to become/stay safer downplayed the risk associated with their
      unprotected sexual encounters. Cognitive variables play an important role in
      influencing sexual risk in MSM both directly and indirectly via risk appraisals.
      Addressing these cognitive processes in HIV prevention interventions may help to
      increase the likelihood of condom use and the accuracy of risk appraisals.

PMID- 23977878
TI  - Ants can be used as bio-indicators to reveal biological effects of
      electromagnetic waves from some wireless apparatus.
AB  - Society is confronted with an increasing number of applications making use of
      wireless communication. We also notice an increasing awareness about potentially
      harmful effects of the related electromagnetic fields on living organisms. At
      present, it is not realistic to expect that wireless communication will decrease
      or disappear within the near future. That is why we currently are investigating
      the mechanisms behind these effects and the effectiveness of possible solutions.
      In order to be efficient and effective, we designed and validated a fast and easy
      test on ants - these insects being used as a biological model - for revealing the
      effect of wireless equipments like mobile phones, smartphones, digital enhanced
      cordless telephone (DECT) phones, WiFi routers and so on. This test includes
      quantification of ants' locomotion under natural conditions, then in the vicinity
      of such wireless equipments. Observations, numerical results and statistical
      results allow detecting any effect of a radiating source on these living
      organisms.

PMID- 23977879
TI  - A methodology to annotate systems biology markup language models with the
      synthetic biology open language.
AB  - Recently, we have begun to witness the potential of synthetic biology, noted here
      in the form of bacteria and yeast that have been genetically engineered to
      produce biofuels, manufacture drug precursors, and even invade tumor cells. The
      success of these projects, however, has often failed in translation and
      application to new projects, a problem exacerbated by a lack of engineering
      standards that combine descriptions of the structure and function of DNA. To
      address this need, this paper describes a methodology to connect the systems
      biology markup language (SBML) to the synthetic biology open language (SBOL),
      existing standards that describe biochemical models and DNA components,
      respectively. Our methodology involves first annotating SBML model elements such
      as species and reactions with SBOL DNA components. A graph is then constructed
      from the model, with vertices corresponding to elements within the model and
      edges corresponding to the cause-and-effect relationships between these elements.
      Lastly, the graph is traversed to assemble the annotating DNA components into a
      composite DNA component, which is used to annotate the model itself and can be
      referenced by other composite models and DNA components. In this way, our
      methodology can be used to build up a hierarchical library of models annotated
      with DNA components. Such a library is a useful input to any future genetic
      technology mapping algorithm that would automate the process of composing DNA
      components to satisfy a behavioral specification. Our methodology for SBML-to
      SBOL annotation is implemented in the latest version of our genetic design
      automation (GDA) software tool, iBioSim. 

PMID- 23977880
TI  - Highly efficient electrochemical responses on single crystalline ruthenium
      vanadium mixed metal oxide nanowires.
AB  - Highly efficient single crystalline ruthenium-vanadium mixed metal oxide (Ru1
      xVxO2, 0<=x<=1) nanowires were prepared on a SiO2 substrate and a commercial Au
      microelectrode for the first time through a vapor-phase transport process by
      adjusting the mixing ratios of RuO2 and VO2 precursors. Single crystalline Ru1
      xVxO2 nanowires show homogeneous solid-solution characteristics as well as the
      distinct feature of having remarkably narrow dimensional distributions. The
      electrochemical observations of a Ru1-xVxO2 (x=0.28 and 0.66)-decorated Au
      microelectrode using cyclic voltammetry (CV) and electrochemical impedance
      spectroscopy (EIS) demonstrate favorable charge-transfer kinetics of [Fe(CN)6]3
      /4- and Ru(NH3)6(3+/2+) couples compared to that of a bare Au microelectrode. The
      catalytic activity of Ru1-xVxO2 for oxygen and H2O2 reduction at neutral pH
      increases as the fraction of vanadium increases within our experimental
      conditions, which might be useful in the area of biofuel cells and biosensors.

PMID- 23977881
TI  - Theoretical study on the ring-opening reactions of cyclopropenes mediated by a
      AuI complex.
AB  - DFT calculations have been carried out in order to rationalize and predict the
      ring-opening regioselectivity of substituted cyclopropenes in the presence of
      gold(I) catalysts. It has been shown that the regioselectivity of these ring
      opening processes is driven by the relative pi-donor ability of the substituents
      on the cyclopropene double bond (C1 and C2). A stronger pi-donor substituent at
      C2 favors Au(I)-induced polarization of the double bond toward C1, resulting in
      preferential breaking of the C1-C3 bond. An excellent correlation between
      DeltaE(++) and the difference in the C1-C2 p(pi) orbital population was observed
      for a broad range of substituents, providing a useful predictive model for gold
      induced cyclopropene ring-opening. Furthermore, it was found that the stability
      of the resulting gold-stabilized allyl-cation intermediates do not follow the
      same trend as the ring-opening reaction energies. Generally, the more facile ring
      opening process led to the less thermodynamically stable intermediate, which
      lacked stabilization of the carbocation by a pi-donor in the alpha-position.

PMID- 23977882
TI  - Anti-apoptosis proteins Mcl-1 and Bcl-xL have different p53-binding profiles.
AB  - One of the transcription-independent mechanisms of the tumor suppressor p53
      discovered in recent years involves physical interaction between p53 and proteins
      of the Bcl-2 family. In this paper, significant differences between the
      interaction of p53 with Mcl-1 and Bcl-xL were demonstrated by NMR spectroscopy
      and isothermal titration calorimetry. Bcl-xL was found to bind strongly to the
      p53 DNA-binding domain (DBD) with a dissociation constant (Kd) of ~600 nM,
      whereas Mcl-1 binds to the p53 DBD weakly with a dissociation constant in the mM
      range. In contrast, the p53 transactivation domain (TAD) binds weakly to Bcl-xL
      with a Kd ~ 300-500 MUM and strongly to Mcl-1 with a Kd ~ 10-20 MUM. NMR
      titrations indicate that although the p53 TAD binds to the BH3-binding grooves of
      both Bcl-xL and Mcl-1, Bcl-xL prefers to bind to the first subdomain (TAD1) in
      the p53 TAD, and Mcl-1 prefers to bind to the second subdomain (TAD2). Therefore,
      Mcl-1 and Bcl-xL have different p53-binding profiles. This indicates that the
      detailed interaction mechanisms are different, although both Mcl-1 and Bcl-xL can
      mediate transcription-independent cytosolic roles of p53. The revealed
      differences in binding sites and binding affinities should be considered when BH3
      mimetics are used in cancer therapy development.

PMID- 23977883
TI  - Inhibition of hypoxia-inducible factor prolyl hydroxylase domain oxygen sensors:
      tricking the body into mounting orchestrated survival and repair responses.
AB  - Hypoxia-inducible factor (HIF) is an oxygen-sensitive dimeric transcription
      factor that responds to pathophysiologically low O2 tensions via up-regulation,
      which leads to an orchestrated biological response to hypoxia. The HIF prolyl
      hydroxylase domain (PHD) enzymes are non-heme, iron-containing dioxygenases
      requiring for activity both molecular oxygen and 2-oxoglutarate that, under
      normoxia, selectively hydroxylate proline residues of HIF, initiating proteosomal
      degradation of the latter. The dependence of HIF protein levels on the
      concentration of O2 present, mediated by the PHD enzymes, forms the basis for one
      of the most significant biological sensor systems of tissue oxygenation in
      response to ischemic and inflammatory events. Consequently, pharmacological
      inhibition of PHD enzymes, leading to stabilization of HIF, may be of
      considerable therapeutic potential in treating conditions of tissue stress and
      injury. This Perspective reviews the PHDs and small molecule drug discovery
      efforts. A critical view of this challenging field is offered, which addresses
      potential concerns and highlights exciting possibilities for the future. 

PMID- 23977884
TI  - Effect of temperature on the deliquescence properties of food ingredients and
      blends.
AB  - Deliquescence is a first-order phase transformation of a crystalline solid to a
      saturated solution that is triggered at a defined relative humidity (RH), RH0.
      Previous studies demonstrated that the RH0 of an inorganic substance with a
      positive heat of solution (DeltaH) will decrease with increases in temperature.
      In this study, the relationships between DeltaH, solubility, and deliquescence RH
      for single-ingredient and multicomponent systems were investigated. The
      deliquescence RHs of inorganic and organic crystalline solids and their mixtures
      were measured at temperatures ranging from 20 to 40  degrees C using a water
      activity meter and various gravimetric moisture sorption analyzers. The
      deliquescence behavior as a function of temperature for organic food ingredients
      was thermodynamically modeled and followed similar trends to those of the
      previously investigated inorganic ingredients. Furthermore, the models can be
      used as a predictive approach to determine physical stability and deliquescence
      RHs of deliquescent ingredients and blends if the storage temperature and
      ingredient DeltaH and solubility are known. 

PMID- 23977887
TI  - Kinematic and kinetic analysis of dogs during trotting after amputation of a
      thoracic limb.
AB  - OBJECTIVE: To characterize biomechanical differences in gait between dogs with
      and without an amputated thoracic limb. ANIMALS: Client-owned dogs (16 thoracic
      limb amputee and 24 quadruped [control] dogs). PROCEDURES: Dogs were trotted
      across 3 in-series force platforms. Spatial kinematic and kinetic data were
      recorded for each limb during the stance phase. RESULTS: Amputees had significant
      increases in stance duration and vertical impulse in all limbs, compared with
      values for control dogs. Weight distribution was significantly increased by 14%
      on the remaining thoracic limb and by a combined 17% on pelvic limbs in amputees.
      Braking ground reaction force (GRF) was significantly increased in the remaining
      thoracic limb and pelvic limb ipsilateral to the amputated limb. The ipsilateral
      pelvic limb had a significantly increased propulsive GRF. The carpus and
      ipsilateral hip and stifle joints had significantly greater flexion during the
      stance phase. The cervicothoracic vertebral region had a significantly increased
      overall range of motion (ROM) in both the sagittal and horizontal planes. The
      thoracolumbar vertebral region ROM increased significantly in the sagittal plane
      but decreased in the horizontal plane. The lumbosacral vertebral region had
      significantly greater flexion without a change in ROM. CONCLUSIONS AND CLINICAL
      RELEVANCE: Compared with results for quadruped dogs, the vertebral column,
      carpus, and ipsilateral hip and stifle joints had significant biomechanical
      changes after amputation of a thoracic limb. The ipsilateral pelvic limb assumed
      dual thoracic and pelvic limb roles because the gait of a thoracic limb amputee
      during trotting appeared to be a mixture of various gait patterns.

PMID- 23977885
TI  - Molecular structure of RADA16-I designer self-assembling peptide nanofibers.
AB  - The designer self-assembling peptide RADA16-I forms nanofiber matrices which have
      shown great promise for regenerative medicine and three-dimensional cell culture.
      The RADA16-I amino acid sequence has a beta-strand-promoting alternating
      hydrophobic/charged motif, but arrangement of beta-strands into the nanofiber
      structure has not been previously determined. Here we present a structural model
      of RADA16-I nanofibers, based on solid-state NMR measurements on samples with
      different schemes for (13)C isotopic labeling. NMR peak positions and line widths
      indicate an ordered structure composed of beta-strands. The NMR data show that
      the nanofibers are composed of two stacked beta-sheets stabilized by a
      hydrophobic core formed by alanine side chains, consistent with previous
      proposals. However, the previously proposed antiparallel beta-sheet structure is
      ruled out by measured (13)C-(13)C dipolar couplings. Instead, neighboring beta
      strands within beta-sheets are parallel, with a registry shift that allows cross
      strand staggering of oppositely charged arginine and aspartate side chains. The
      resulting structural model is compared to nanofiber dimensions observed via
      images taken by transmission electron microscopy and atomic force microscopy.
      Multiple NMR peaks for each alanine side chain were observed and could be
      attributed to multiple configurations of side chain packing within a single
      scheme for intermolecular packing. 

PMID- 23977888
TI  - Kinematic and kinetic analysis of dogs during trotting after amputation of a
      pelvic limb.
AB  - OBJECTIVE: To evaluate biomechanical gait adaptations in dogs after amputation of
      a pelvic limb. ANIMALS: Client-owned dogs (12 pelvic limb-amputee and 24
      quadruped [control] dogs). PROCEDURES: Dogs were trotted across 3 in-series force
      platforms. Spatial kinematic and kinetic data were recorded for each limb during
      the stance phase. RESULTS: Pelvic limb amputees had increased peak braking forces
      in the contralateral thoracic limb and increased propulsive forces and impulses
      in both the ipsilateral thoracic limb and remaining pelvic limb. Time to peak
      braking force was significantly decreased, and time to peak propulsive force was
      significantly increased in all remaining limbs in amputees. Amputees had an
      increase in range of motion at the tarsal joint of the remaining pelvic limb,
      compared with results for the control dogs. Amputees had increased vertebral
      range of motion at T1 and T13 and increased vertebral extension at L7 within the
      sagittal plane. In the horizontal plane, amputees had increased lateral bending
      toward the remaining pelvic limb, which resulted in a laterally deviated gait
      pattern. CONCLUSIONS AND CLINICAL RELEVANCE: Pelvic limb amputees adjusted to
      loss of a limb through increased range of motion at the tarsal joint, increased
      range of motion in the cervicothoracic and thoracolumbar vertebral regions, and
      extension of the lumbosacral vertebral region, compared with results for the
      control dogs. Amputees alternated between a laterally deviated gait when the
      pelvic limb was in propulsion and a regular cranially oriented gait pattern when
      either forelimb was in propulsion with horizontal rotation around L7.

PMID- 23977889
TI  - Computed tomographic method for measurement of inclination angles and motion of
      the sacroiliac joints in German Shepherd Dogs and Greyhounds.
AB  - OBJECTIVE: To develop an in vivo CT method to measure inclination angles and
      motion of the sacroiliac joints in dogs of performance breeds. ANIMALS: 10 German
      Shepherd Dogs and 12 Greyhounds without signs of lumbosacral region pain or
      neurologic problems. PROCEDURES: CT of the ilium and sacrum was performed in
      flexed, neutral, and extended hind limb positions. Lines were drawn on volume
      rendered images acquired in the flexed and extended positions to measure motion
      of the ilia relative to the sacra. Inclination angles of the synovial and
      ligamentous components of the sacroiliac joints were measured on transverse-plane
      CT images acquired at cranial and caudal locations. Coefficients of variance of
      measurements were calculated to determine intraobserver variability. RESULTS:
      Coefficients of variance of measurements ranged from 0.17% to 2.45%. A
      significantly higher amount of sacroiliac joint rotational motion was detected
      for German Shepherd Dogs versus Greyhounds. The cranial synovial joint component
      had a significantly more sagittal orientation in German Shepherd Dogs versus
      Greyhounds. No significant differences were detected between breeds for x- or y
      axis translational motion or caudal synovial or ligamentous joint component
      inclination angles. CONCLUSIONS AND CLINICAL RELEVANCE: The small amounts of
      sacroiliac joint motion detected in this study may buffer high-frequency
      vibrations during movement of dogs. Differences detected between breeds may be
      associated with the predisposition of German Shepherd Dogs to develop lumbosacral
      region signs of pain, although the biological importance of this finding was not
      determined. Future studies are warranted to compare sacroiliac joint variables
      between German Shepherd Dogs with and without lumbosacral region signs of pain.

PMID- 23977890
TI  - Effect of forelimb lameness on hoof kinematics of horses at a trot.
AB  - OBJECTIVE: To determine kinematic changes to the hoof of horses at a trot after
      induction of unilateral, weight-bearing forelimb lameness and to determine
      whether hoof kinematics return to prelameness values after perineural anesthesia.
      ANIMALS: 6 clinically normal Quarter Horses. PROCEDURES: For each horse, a sole
      pressure model was used to induce 3 grades (grades 1, 2, and 3) of lameness in
      the right forelimb, after which perineural anesthesia was administered to
      alleviate lameness. Optical kinematics were obtained for both forelimbs with the
      horse trotting before (baseline) and after induction of each grade of lameness
      and after perineural anesthesia. Hoof events were identified with linear
      acceleration profiles, and each stride was divided into hoof-contact, break-over,
      initial-swing, terminal-swing, and total-swing segments. For each segment,
      kinematic variables were compared within and between limbs by use of mixed
      repeated-measures ANOVA. RESULTS: During hoof-contact, the left (nonlame)
      forelimb hoof had greater heel-down orientation than did the right (lame)
      forelimb hoof, and during break-over, the nonlame hoof went through a larger
      range of motion than did the lame hoof. Maximum cranial acceleration during break
      over for the lame hoof was greater, compared with that at baseline or for the
      nonlame hoof. Following perineural anesthesia, the sagittal plane orientation of
      the hoof during hoof-contact did not vary between the lame and nonlame limbs;
      however, interlimb differences in maximum cranial acceleration and angular range
      of motion during break-over remained. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggested that hoof kinematics may be useful for detection of unilateral, weight
      bearing forelimb lameness in horses that are trotting.

PMID- 23977891
TI  - Effect of forelimb lameness on hoof kinematics of horses at a walk.
AB  - OBJECTIVE: To determine kinematic changes to the hoof of horses at a walk after
      induction of unilateral, weight-bearing forelimb lameness and to determine
      whether hoof kinematics return to prelameness (baseline) values after perineural
      anesthesia. ANIMALS: 6 clinically normal Quarter Horses. PROCEDURES: For each
      horse, a sole-pressure model was used to induce 3 grades of lameness in the right
      forelimb, after which perineural anesthesia was administered to eliminate
      lameness. Optical kinematics were obtained for both forelimbs with the horse
      walking before (baseline) and after induction of each grade of lameness and after
      perineural anesthesia. Linear acceleration profiles were used to identify hoof
      events, and each stride was divided into hoof-contact, break-over, initial-swing,
      terminal-swing, and total-swing segments. Kinematic variables were compared
      within and between limbs for each segment by use of mixed repeated-measures
      ANOVA. RESULTS: During the hoof-contact and terminal-swing segments, the hoof of
      the left (nonlame) forelimb had greater sagittal-plane orientation than did the
      hoof of the right (lame) forelimb. For the lame limb following lameness
      induction, the break-over duration and maximum cranial acceleration were
      increased from baseline. After perineural anesthesia, break-over duration for the
      lame limb returned to a value similar to that at baseline, and orientation of the
      hoof during the terminal-swing segment did not differ between the lame and
      nonlame limbs. CONCLUSIONS AND CLINICAL RELEVANCE: Subclinical unilateral
      forelimb lameness resulted in significant alterations to hoof kinematics in
      horses that are walking, and the use of hoof kinematics may be beneficial for the
      detection of subclinical lameness in horses.

PMID- 23977892
TI  - In vitro effects of meloxicam on metabolism in articular chondrocytes from dogs
      with naturally occurring osteoarthritis.
AB  - OBJECTIVE: To assess effects of in vitro meloxicam exposure on metabolism in
      articular chondrocytes from dogs with naturally occurring osteoarthritis. SAMPLE:
      Femoral head cartilage from 16 dogs undergoing total hip replacement. PROCEDURES:
      Articular cartilage samples were obtained. Tissue sulfated glycosaminoglycan
      (SGAG), collagen, and DNA concentrations were measured. Collagen, SGAG,
      chondroitin sulfate 846, NO, prostaglandin E2 (PGE2), and matrix
      metalloproteinase (MMP)-2, MMP-3, MMP-9, and MMP-13 concentrations in culture
      medium were analyzed. Aggrecan, collagen II, MMP-2, MMP-3, MMP-9, MMP-13, ADAM
      metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4, ADAMTS-5, tissue
      inhibitor of metalloproteinase (TIMP)-1, TIMP-2, TIMP-3, interleukin-1beta, tumor
      necrosis factor-alpha, cyclooxygenase-1, cyclooxygenase-2, and inducible nitric
      oxide synthase gene expression were evaluated. Comparisons between tissues
      cultured without (control) and with meloxicam at concentrations of 0.3, 3.0, and
      30.0 MUg/mL for up to 30 days were performed by means of repeated-measures
      analysis. RESULTS: Meloxicam had no effect on chondrocyte SGAG, collagen, or DNA
      concentrations. Expression of ADAMTS-5 was significantly decreased in all groups
      on all days, compared with the day 0 value. On day 3, culture medium PGE2
      concentrations were significantly lower in all meloxicam-treated groups, compared
      with values for controls, and values remained low. Culture medium MMP-3
      concentrations were significantly lower on day 30 than on day 3 in all meloxicam
      treated groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in
      vitro meloxicam treatment of osteoarthritic canine cartilage for up to 30 days
      did not induce matrix degradation or stimulate MMP production. Meloxicam lowered
      PGE2 release from this tissue, and effects on tissue chondrocyte content and
      matrix composition were neutral.

PMID- 23977893
TI  - Validation of a commercially available enzyme immunoassay for measurement of
      plasma antidiuretic hormone concentration in healthy dogs and assessment of
      plasma antidiuretic hormone concentration in dogs with congestive heart failure.
AB  - OBJECTIVE: To validate the use of a human enzyme immunoassay (EIA) kit for
      measurement of plasma antidiuretic hormone (ADH) concentration in dogs and
      evaluate plasma ADH concentrations in dogs with congestive heart failure (CHF)
      attributable to acquired cardiac disease, compared with findings in healthy dogs.
      ANIMALS: 6 healthy dogs and 12 dogs with CHF as a result of chronic degenerative
      valve disease or dilated cardiomyopathy. PROCEDURES: Plasma samples from the 6
      healthy dogs were pooled and used to validate the EIA kit for measurement of
      plasma ADH concentration in dogs by assessing intra-assay precision, dilutional
      linearity, and spiking recovery. Following validation, plasma ADH concentrations
      were measured in the 6 healthy dogs and in the 12 dogs with CHF for comparison.
      RESULTS: The EIA kit measured ADH concentrations in canine plasma samples with
      acceptable intra-assay precision, dilutional linearity, and spiking recovery. The
      intra-assay coefficient of variation was 11%. By use of this assay, the median
      plasma concentration of ADH in dogs with CHF was 6.15 pg/mL (SD, 3.2 pg/mL;
      range, 4.18 to 15.47 pg/mL), which was significantly higher than the median
      concentration in healthy dogs (3.67 pg/mL [SD, 0.93 pg/mL; range, 3.49 to 5.45
      pg/mL]). CONCLUSIONS AND CLINICAL RELEVANCE: Plasma ADH concentrations in dogs
      can be measured with the tested EIA kit. Plasma ADH concentrations were higher in
      dogs with CHF induced by acquired cardiac disease than in healthy dogs. This
      observation provides a basis for future studies evaluating circulating ADH
      concentrations in dogs with developing heart failure.

PMID- 23977894
TI  - Effects of clopidogrel on the platelet activation response in horses.
AB  - OBJECTIVE: To evaluate the platelet activation response before and after
      treatment with clopidogrel in horses. ANIMALS: 12 healthy adult mares.
      PROCEDURES: In a masked study, horses (6/group) were randomly allocated to
      alternately receive placebo or clopidogrel via nasogastric tube at a loading dose
      of 4 mg/kg followed by 2 mg/kg every 24 hours. Blood samples were collected
      before and 72 hours after initiation of treatment for ADP- and collagen-induced
      light transmission aggregometry; determination of closure time in collagen-ADP
      cartridges; modified thrombelastography for comparison of maximal amplitudes
      generated by kaolin, reptilase, and reptilase plus ADP activation; and flow
      cytometric tests to detect platelet fibrinogen binding, P-selectin expression,
      and phosphatidylserine externalization before and after ex vivo stimulation with
      thrombin, convulxin, thrombin with convulxin, and calcium ionophore. RESULTS:
      Clopidogrel administration induced a significant decrease in mean aggregation
      response to 5 MUM and 10 MUM ADP stimulation; however, 2 horses had resistance to
      clopidogrel's inhibitory action. Significant differences after clopidogrel
      treatment were not found in any other tests of platelet function. CONCLUSIONS AND
      CLINICAL RELEVANCE: Assays using commercially available reagents were configured
      to measure different variables of the platelet activation response; however,
      clopidogrel's platelet inhibitory action was only detected by ADP-induced light
      transmission aggregometry. Results also suggested that horses, like humans, have
      interindividual variability in response to clopidogrel that may influence the
      drug's clinical efficacy as an antiplatelet agent.

PMID- 23977895
TI  - Assessment of left ventricular volumes by use of one-, two-, and three
      dimensional echocardiography versus magnetic resonance imaging in healthy dogs.
AB  - OBJECTIVE: To quantify left ventricle (LV) volumes by use of 1-D, 2-D, and 3-D
      echocardiography versus MRI in dogs. ANIMALS: 10 healthy Beagles. PROCEDURES:
      During anesthesia, each dog underwent an echocardiographic examination via the
      Teichholz method, performed on the basis of standard M-mode frames (1-D); the
      monoplane Simpson method of disk (via 2-D loops); real-time triplane
      echocardiography (RTTPE) with a 3-D probe; and real-time 3-D echocardiography
      with a 3-D probe. Afterward, cardiac MRI was performed. Values for the LV end
      diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF)
      were compared between each echocardiographic method and the reference method
      (cardiac MRI). RESULTS: No significant differences for EDV, ESV, and EF were
      detected between RTTPE and cardiac MRI. Excellent correlations (r = 0.97, 0.98,
      and 0.95 for EDV, ESV, and EF, respectively) were found between RTTPE and values
      for cardiac MRI. The other echocardiographic methods yielded values significantly
      different from cardiac MRI and results correlated less well with results of
      cardiac MRI for EDV, ESV, and EF. Use of the Teichholz method resulted in LV
      volume overestimation, whereas the Simpson method of disk and real-time 3-D
      echocardiography significantly underestimated LV volumes. CONCLUSIONS AND
      CLINICAL RELEVANCE: Use of RTTPE yielded excellent correlations and
      nonsignificant differences with cardiac MRI and is a suitable method for routine
      veterinary cardiac examination.

PMID- 23977896
TI  - Effects of exercise on markers of venous remodeling in lungs of horses.
AB  - OBJECTIVE: To determine the effects of 2 weeks of intense exercise on expression
      of markers of pulmonary venous remodeling in the caudodorsal and cranioventral
      regions of the lungs of horses. ANIMALS: 6 horses. PROCEDURES: Tissue samples of
      the caudodorsal and cranioventral regions of lungs were obtained before and after
      conditioning and 2 weeks of intense exercise. Pulmonary veins were isolated, and
      a quantitative real-time PCR assay was used to determine mRNA expression of
      matrix metalloproteinase-2 and -9, tissue inhibitor of metalloproteinase-1 and 
      2, collagen type I, tenascin-C, endothelin-1, platelet-derived growth factor,
      transforming growth factor (TGF)-beta, and vascular endothelial growth factor
      (VEGF). Protein expression of collagen (via morphometric analysis) and tenascin
      C, TGF-beta, and VEGF (via immunohistochemistry) was determined. RESULTS:
      Exercise-induced pulmonary hemorrhage was detected in 2 horses after exercise.
      The mRNA expression of matrix metalloproteinase-2 and -9, tissue inhibitor of
      metalloproteinase-2, TGF-beta, and VEGF was significantly lower in pulmonary
      veins obtained after exercise versus those obtained before exercise for both the
      caudodorsal and cranioventral regions of the lungs. Collagen content was
      significantly higher in tissue samples obtained from the caudodorsal regions of
      the lungs versus content in samples obtained from the cranioventral regions of
      the lungs both before and after exercise. Exercise did not alter protein
      expression of tenascin-C, TGF-beta, or VEGF. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results of this study indicated 2 weeks of intense exercise did not alter
      expression of marker genes in a manner expected to favor venous remodeling.
      Pulmonary venous remodeling is complex, and > 2 weeks of intense exercise may be
      required to induce such remodeling.

PMID- 23977897
TI  - Qualitative and quantitative interpretation of computed tomography of the lungs
      in healthy neonatal foals.
AB  - OBJECTIVE: To qualitatively describe lung CT images obtained from sedated healthy
      equine neonates (<= 14 days of age), use quantitative analysis of CT images to
      characterize attenuation and distribution of gas and tissue volumes within the
      lungs, and identify differences between lung characteristics of foals <= 7 days
      of age and foals > 7 days of age. ANIMALS: 10 Standardbred foals between 2.5 and
      13 days of age. PROCEDURES: Foals were sedated with butorphanol, midazolam, and
      propofol and positioned in sternal recumbency for thoracic CT. Image analysis
      software was used to exclude lung from nonlung structures. Lung attenuation was
      measured in Hounsfield units (HU) for analysis of whole lung and regional changes
      in attenuation and lung gas and tissue components. Degree of lung attenuation was
      classified as follows: hyperinflated or emphysema, -1,000 to -901 HU; well
      aerated, -900 to -501 HU; poorly aerated, -500 to -101 HU; and nonaerated, > -100
      HU. RESULTS: Qualitative evidence of an increase in lung attenuation and patchy
      alveolar patterns in the ventral lung region were more pronounced in foals <= 7
      days of age than in older foals. Quantitative analysis revealed that mean +/- SD
      lung attenuation was greater in foals <= 7 days of age (-442 +/- 28 HU) than in
      foals > 7 days of age (-521 +/- 24 HU). Lung aeration and gas volumes were lower
      than in other regions ventrally and in the mid lung region caudal to the heart.
      CONCLUSIONS AND CLINICAL RELEVANCE-Identified radiographic patterns and changes
      in attenuation were most consistent with atelectasis and appeared more severe in
      foals <= 7 days of age than in older neonatal foals. Recognition of these changes
      may have implications for accurate CT interpretation in sedated neonatal foals
      with pulmonary disease.

PMID- 23977898
TI  - Effects of oxygen insufflation rate, respiratory rate, and tidal volume on
      fraction of inspired oxygen in cadaveric canine heads attached to a lung model.
AB  - OBJECTIVE: To assess the effects of oxygen insufflation rate, respiratory rate,
      and tidal volume on fraction of inspired oxygen (Fio2) in cadaveric canine heads
      attached to a lung model. SAMPLE: 16 heads of canine cadavers. PROCEDURES: Each
      cadaver head was instrumented with a nasal insufflation catheter through which
      oxygen was delivered. The trachea was attached to a sample collection port
      connected by means of corrugated tubing to a lung model. Eight treatment
      combinations that varied in respiratory rate (10 or 20 breaths/min), tidal volume
      (10 or 15 mL/kg), and oxygen insufflation rate (50 or 100 mL/kg/min) were applied
      to each head in a replicated Latin square design. Gas samples were manually
      collected, and inspired oxygen concentrations were analyzed. The Fio2 and end
      tidal CO2 concentration were determined and compared among sample groups.
      RESULTS: Estimated least squares mean Fio2 for various treatment combinations
      ranged from 32.2% to 60.6%. The Fio2 was significantly increased at the higher
      insufflation rate (estimated marginal least squares mean, 48.7% vs 38.6% for 100
      and 50 mL/kg/min, respectively), lower respiratory rate (48.9% vs 38.3% for 10
      and 20 breaths/min, respectively), and smaller tidal volume (46.8% vs 40.0% for
      10 and 15 mL/kg, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: -Fio2 in the
      model was affected by oxygen insufflation rate, respiratory rate, and tidal
      volume. This information may potentially help clinicians interpret results of
      blood gas analysis and manage canine patients receiving oxygen insufflation via a
      nasal catheter.

PMID- 23977899
TI  - Electronic properties of fluorosulfonyl isocyanate, FSO2NCO: a photoelectron
      spectroscopy and synchrotron photoionization study.
AB  - The electronic properties of fluorosulfonyl isocyanate, FSO2NCO, were
      investigated by means of photoelectron spectroscopy and synchrotron based
      techniques. The first ionization potential occurs at 12.3 eV and was attributed
      to the ejection of electrons formally located at the pi NCO molecular orbital
      (MO), with a contribution from nonbonding orbitals at the oxygen atoms of the SO2
      group. The proposed interpretation of the photoelectron spectrum is consistent
      with related molecules reported previously and also with the prediction of OVGF
      (outer valence green function) and P3 (partial third order) calculations. The
      energy of the inner- and core-shell electrons was determined using X-ray
      absorption, measuring the total ion yield spectra, and the resonances before each
      ionization threshold were interpreted in terms of transitions to vacant molecular
      orbitals. The ionic fragmentation mechanisms in the valence energy region were
      studied using time-of-flight mass spectrometry as a function of the energy of the
      incident radiation. At 13 eV the M(+) was the only ion detected in the photoion
      photoelectron-coincidence spectrum, while the FSO2(+) fragment, formed through
      the breaking of the S-N single bond, appears as the most intense fragment for
      energies higher than 15 eV. The photoion-photoion-photoelectron-coincidence
      spectra, taken at the inner- and core-levels energy regions, revealed several
      different fragmentation pathways, being the most important ones secondary decay
      after deferred charge separation mechanisms leading to the formation of the
      O(+)/S(+) and C(+)/O(+) pairs. 

PMID- 23977900
TI  - Recyclable functionalization of silica with alcohols via dehydrogenative addition
      on hydrogen silsesquioxane.
AB  - Synthesis of class II hybrid silica materials requires the formation of covalent
      linkage between organic moieties and inorganic frameworks. The requirement that
      organosilylating agents be present to provide the organic part limits the
      synthesis of functional inorganic oxides, however, due to the water sensitivity
      and challenges concerning purification of the silylating agents. Synthesis of
      hybrid materials with stable molecules such as simple alcohols, rather than with
      these difficult silylating agents, may therefore provide a path to unprecedented
      functionality. Herein, we report the novel functionalization of silica with
      organic alcohols for the first time. Instead of using hydrolyzable
      organosilylating agents, we used stable organic alcohols with a Zn(II) catalyst
      to modify the surface of a recently discovered highly reactive macro-mesoporous
      hydrogen silsesquioxane (HSQ, HSiO1.5) monolith, which was then treated with
      water with the catalyst to form surface-functionalized silica. These materials
      were comprehensively characterized with FT-IR, Raman, solid-state NMR,
      fluorescence spectroscopy, thermal analysis, elemental analysis, scanning
      electron microscopy, and nitrogen adsorption-desorption measurements. The results
      obtained from these measurements reveal facile immobilization of organic moieties
      by dehydrogenative addition onto surface silane (Si-H) at room temperature with
      high loading and good tolerance of functional groups. The organic moieties can
      also be retrieved from the monoliths for recycling and reuse, which enables cost
      effective and ecological use of the introduced catalytic/reactive surface
      functionality. Preservation of the reactivity of as-immobilized organic alcohols
      has been confirmed, moreover, by successfully performing copper-catalyzed azide
      alkyne cycloaddition (CuAAC) "click" reactions on the immobilized silica
      surfaces. 

PMID- 23977901
TI  - Self-assembly of amphiphilic homopolymers bearing ferrocene and carboxyl
      functionalities: effect of polymer concentration, beta-cyclodextrin, and length
      of alkyl linker.
AB  - Three new acrylamide monomers containing ferrocene and tert-butyl ester groups
      were first synthesized via multistep nucleophilic substitution reaction under
      mild conditions followed by reversible addition-fragmentation chain transfer
      (RAFT) homopolymerization to give well-defined homopolymers with narrow molecular
      weight distributions (M(w)/M(n) <= 1.36). The target amphiphilic homopolymers
      were obtained by the acidic hydrolysis of tert-butyoxycarbonyls to carboxyls in
      every repeating unit using CF3COOH. The self-assembly behaviors of these
      amphiphilic homopolymers bearing both ferrocene and carboxyl moieties in each
      repeating unit in aqueous media were investigated by transmission emission
      microscopy (TEM), dynamic light scattering (DLS), and atomic force microscopy
      (AFM). Large compound micelles with different morphologies were formed by these
      amphiphilic homopolymers, which consist of the corona formed by hydrophilic
      carboxyls and the core containing numerous reverse micelles with hydrophilic
      islands of carboxyls in continuous hydrophobic phase of ferrocene-based segments.
      The morphologies of the formed micelles could be tuned by the concentration of
      amphiphilic homopolymers, pH value of the solution, the length of -CH2 linker
      between ferrocene group and carboxyl, and the amount of beta-cyclodextrin (beta
      CD).

PMID- 23977902
TI  - Two-dimensional fluorescence lifetime correlation spectroscopy. 2. Application.
AB  - In the preceding article, we introduced the theoretical framework of two
      dimensional fluorescence lifetime correlation spectroscopy (2D FLCS). In this
      article, we report the experimental implementation of 2D FLCS. In this method,
      two-dimensional emission-delay correlation maps are constructed from the photon
      data obtained with the time-correlated single photon counting (TCSPC), and then
      they are converted to 2D lifetime correlation maps by the inverse Laplace
      transform. We develop a numerical method to realize reliable transformation,
      employing the maximum entropy method (MEM). We apply the developed actual 2D FLCS
      to two real systems, a dye mixture and a DNA hairpin. For the dye mixture, we
      show that 2D FLCS is experimentally feasible and that it can identify different
      species in an inhomogeneous sample without any prior knowledge. The application
      to the DNA hairpin demonstrates that 2D FLCS can disclose microsecond spontaneous
      dynamics of biological molecules in a visually comprehensible manner, through
      identifying species as unique lifetime distributions. A FRET pair is attached to
      the both ends of the DNA hairpin, and the different structures of the DNA hairpin
      are distinguished as different fluorescence lifetimes in 2D FLCS. By constructing
      the 2D correlation maps of the fluorescence lifetime of the FRET donor, the
      equilibrium dynamics between the open and the closed forms of the DNA hairpin is
      clearly observed as the appearance of the cross peaks between the corresponding
      fluorescence lifetimes. This equilibrium dynamics of the DNA hairpin is clearly
      separated from the acceptor-missing DNA that appears as an isolated diagonal peak
      in the 2D maps. The present study clearly shows that newly developed 2D FLCS can
      disclose spontaneous structural dynamics of biological molecules with microsecond
      time resolution. 

PMID- 23977903
TI  - Triple-layered perovskite niobates CaRNb3O10 (R = La, Sm, Eu, Gd, Dy, Er, Yb, or
      Y): new self-activated oxides.
AB  - Niobates CaRNb3O10 (R = La, Sm, Eu, Gd, Dy, Er, Yb, or Y) were prepared by
      conventional high-temperature solid-state reaction. The formation of a single
      phase compound with triple-layered perovskite-type structure was verified through
      X-ray diffraction (XRD) studies. The luminescence characteristics such as
      photoluminescence excitation and emission spectra, X-ray-excited luminescence
      (XEL), Stokes shift, decay curves, and color coordinates were investigated. The
      niobates can be efficiently excited by UV light and present luminescence
      behaviors with rich luminescence colors. Under excitation by ultraviolet
      radiation, CaRNb3O10 (R = La, Gd, Yb, or Y) exhibits strong blue luminescence due
      to the self-activation center of the octahedral NbO6 groups, even at room
      temperature. For the materials of composition CaRNb3O10 (R = Sm, Eu, Dy, or Er),
      the excitation at the host band produces a characteristic luminescence of rare
      earth ions, indicating a host-guest energy transfer process. CaRNb3O10 (R = Eu)
      has the strongest luminescence intensity, which can be efficiently excitated by
      near UV wavelength. It could be suggested to be a potential candidate for the
      application on near-UV excited white LEDs. 

PMID- 23977905
TI  - The cuffed endotracheal tube.

PMID- 23977904
TI  - Malaria diagnosis and treatment practices following introduction of rapid
      diagnostic tests in Kibaha District, Coast Region, Tanzania.
AB  - BACKGROUND: The success of the universal parasite-based malaria testing policy
      for fever patients attending primary health care (PHC) facilities in Tanzania
      will depend highly on health workers' perceptions and practices. The aim of this
      study was, therefore, to assess the present use of malaria diagnostics (rapid
      diagnostic tests (RDTs) and microscopy), prescription behaviour and factors
      affecting adherence to test results at PHC facilities in Kibaha District, Coast
      Region, Tanzania. METHODS: Exit interviews were conducted with fever patients at
      PHC facilities and information on diagnostic test performed and treatment
      prescribed were recorded. Interviews with prescribers to assess their
      understanding, perceptions and practices related to RDTs were conducted, and
      health facility inventory performed to assess availability of staff, diagnostics
      and anti-malarial drugs. RESULTS: The survey was undertaken at ten governmental
      PHC facilities, eight of which had functional diagnostics. Twenty health workers
      were interviewed and 195 exit interviews were conducted with patients at the PHC
      facilities. Of the 168 patients seen at facilities with available diagnostics,
      105 (63%) were tested for malaria, 31 (30%) of whom tested positive. Anti
      malarial drugs were prescribed to all patients with positive test results, 14% of
      patients with negative results and 28% of patients not tested for malaria.
      Antibiotics were more likely to be prescribed to patients with negative test
      results compared to patients with positive results (81 vs 39%, p < 0.01) and
      among non-tested compared to those tested for malaria (84 vs 69%, p = 0.01).
      Stock-outs of RDTs and staff shortage accounted for the low testing rate, and
      health worker perceptions were the main reason for non-adherence to test results.
      CONCLUSIONS: Anti-malarial prescription to patients with negative test results
      and those not tested is still practiced in Tanzania despite the universal malaria
      testing policy of fever patients. The use of malaria diagnostics was also
      associated with higher prescription of antibiotics among patients with negative
      results. Strategies to address health system factors and health worker
      perceptions associated with these practices are needed.

PMID- 23977906
TI  - Medical co-management of high risk surgical patients.

PMID- 23977907
TI  - Differential associations between body mass index and outcomes after elective
      adult cardiac surgery: a linked data cohort study.
AB  - This study assessed the relationships between body mass index (BMI) and different
      outcomes after adult cardiac surgery by linking detailed preoperative comorbidity
      data with the long-term mortality and morbidity outcomes of 2131 consecutive
      patients who had elective cardiac surgery at a major cardiac surgical hospital in
      Western Australia. Patients with a high BMI had more comorbidities and were more
      likely to have had coronary artery bypass grafting than valve surgery. A total of
      143 patients (6.7%) died during a median follow-up period of 30 months. The major
      causes of death were congestive heart failure (25.9%), myocardial infarction
      (14.7%), infection (23.8%) and cancer (13.9%). BMI had no association with long
      term mortality, after adjusting for important confounders including the Charlson
      Comorbidity Index. BMI had a relatively linear relationship with the risk of new
      onset atrial fibrillation (odds ratio 1.05 per point increment, 95% confidence
      interval 1.03 to 1.05) and venous thromboembolism (odds ratio 1.20, 95%
      confidence interval 1.14 to 1.26). BMI was the second most important predictor
      after age and accounted for 22% of the variability in the risk of atrial
      fibrillation. BMI had an inverse relationship with the risk of requiring
      allogeneic blood transfusion, postoperative intra-aortic balloon pump, or
      surgical re-exploration. In summary, BMI had differential associations with
      different short- and long-term outcomes after elective adult cardiac surgery.
      After adjusting for important confounders including the presence of cancers, we
      did not observe any 'obesity paradox' and patients with a high BMI were not
      associated with an increased probability of long-term survival. 

PMID- 23977908
TI  - Type 2 diabetes mellitus, independent of insulin use, is associated with an
      increased risk of cardiac complications after vascular surgery.
AB  - Previous reports on the prognostic value of diabetes mellitus for cardiac
      complications after vascular surgery show divergent results, especially in
      regards to the role of type 2 diabetes as a cardiac risk factor, which remains
      unclear. The aim of this study was to assess the impact of type 2 diabetes on 30
      day cardiac complications after vascular surgery. Patients undergoing elective
      vascular surgery between 2002 and 2011 were included in this retrospective cohort
      study. Previous diagnosis of type 1 and 2 diabetes and use of oral glucose
      lowering medications and insulin were recorded. Patients with type 1 diabetes
      were excluded from the analysis. The main outcome parameter was cardiac
      complications, a composite of cardiovascular death, non-fatal myocardial
      infarction, congestive heart failure, severe arrhythmia and asymptomatic troponin
      release within 30 days of surgery. In multivariate analysis, corrections were
      made for comorbidities, demographics, medication use and surgical risk. Of 1462
      patients, 329 (22.5%) patients had type 2 diabetes. Cardiac complications
      occurred in 155 (13.7%) patients without diabetes and in 68 (20.7%) with type 2
      diabetes. In multivariate analysis, type 2 diabetes was associated with a
      significantly increased risk of 30-day cardiac complications (odds ratio 1.80;
      95% confidence interval 1.25 to 2.60). Results were similar for type 2 diabetes
      patients managed with (odds ratio 1.84; 95% confidence interval 1.01 to 3.37) and
      without (odds ratio 1.79; 95% confidence interval 1.19 to 2.70) insulin. Type 2
      diabetes is an independent risk factor for cardiac complications after vascular
      surgery and should be treated as such in preoperative cardiac risk
      stratification. 

PMID- 23977909
TI  - A preliminary evaluation of plasma b-type natriuretic peptide as a screening test
      for left ventricular diastolic dysfunction in non-cardiac intensive care.
AB  - Left ventricular filling and thus diastolic function are frequently monitored and
      managed in critical care. However, scant data exist regarding possible screening
      tests for diastolic dysfunction in the intensive care unit (ICU). The present
      study aimed to evaluate plasma b-type natriuretic peptide (BNP) as a marker of
      diastolic dysfunction in a single-centre cohort of 'non-cardiac' ICU patients.
      The ICU is non-cardiac in that it provides mixed medical/surgical services with
      the exception of cardiology, cardiac surgery and solid organ transplantation.
      Clinical data were recorded over the first 24 hours of ICU stay for 32
      consecutive patients. Transthoracic echocardiogram and blood collection for BNP
      assay were then performed. Diastolic dysfunction was demonstrated in 34% (n=11).
      Mean +/- standard deviation BNP values were higher with diastolic dysfunction
      (238 +/- 195 vs 72 +/- 78 pg/ml; P=0.003). A BNP threshold of >43 pg/ml yielded a
      sensitivity of 80% and a specificity of 59%; area under the receiver operating
      characteristic curve was 0.82. BNP correlated independently with E/e' (R=0.425;
      P=0.015) (E/e': peak early transmitral velocity [E]/early diastolic mitral
      annular velocity [e']) but not left ventricular ejection fraction (P=0.8),
      illness severity (Acute Physiological and Chronic Health Evaluation II; P=0.3) or
      fluid balance (P=0.4). Diastolic dysfunction was common in this cohort of non
      cardiac ICU patients and was independently associated with a significantly higher
      BNP. The potential application as a screening test for diastolic dysfunction is
      likely to require a threshold lower than previously proposed for heart failure.

PMID- 23977910
TI  - Duration of cortisol suppression following a single dose of dexamethasone in
      healthy volunteers: a randomised double-blind placebo-controlled trial.
AB  - The synthetic glucocorticoid dexamethasone is administered to many patients
      receiving a general anaesthetic to reduce the risk of postoperative nausea and
      vomiting. Dexamethasone is known to suppress the hypothalamic-pituitary-adrenal
      axis; however, the duration of this suppression following the standard anti
      emetic intravenous dose of 4 to 8 mg used with anaesthesia is unknown. A
      randomised controlled double-blind crossover trial assessing the effects of 8 mg
      intravenous dexamethasone versus saline control was performed in ten healthy male
      volunteers. The adrenal, thyroid and gonadal axes and glucose levels were
      assessed over a four-day period after dexamethasone administration. All
      participants had normal baseline hypothalamic-pituitary-adrenal axis function. No
      difference in cortisol levels was demonstrated at four or eight hours after
      dexamethasone administration compared with placebo. At 24 hours post
      dexamethasone, the cortisol had dropped to less than 5% of baseline and returned
      to normal during the subsequent day. Increased plasma glucose levels were also
      observed in the dexamethasone group as compared with placebo. A dose of 8 mg of
      dexamethasone results in significant suppression of the hypothalamic-pituitary
      adrenal axis and elevated plasma glucose levels. The cortisol suppression is
      maximal at approximately 24 hours post dose. 

PMID- 23977911
TI  - Phenytoin loading doses in adult critical care patients: does current practice
      achieve adequate drug levels?
AB  - Phenytoin is regularly employed in the critically ill for prophylaxis against or
      treatment of seizure disorders. No prior studies have examined current dosing
      practices in an Australasian intensive care unit (ICU) setting. The aims of this
      study were to: a) describe the adequacy of contemporary dosing in respect to free
      and total serum phenytoin concentrations; b) identify factors associated with
      therapeutic drug concentrations; and c) examine the accuracy of predictive
      equations that estimate free concentrations in this setting. All patients
      receiving a loading dose of phenytoin in a tertiary-level ICU were eligible for
      enrolment; 53 patients were enrolled in the study. Serum samples to determine
      free and total phenytoin concentrations (measured by high performance liquid
      chromatography) were then drawn prior to the following dose. Free concentrations
      below the recommended target (<1 mg/l) were considered as suboptimal. The most
      common indication for phenytoin loading was traumatic brain injury (49%) and the
      mean administered dose was 14.5 (3.66) mg/kg. Twenty-six patients (49%) had
      suboptimal trough free concentrations, although this subgroup was significantly
      heavier and therefore received a lower per kilogram dose (12.8 [3.1] vs 16.3
      [3.4] mg/kg, P=0.001). In multivariate analysis, larger weight adjusted doses
      (P=0.018), higher albumin concentration (P=0.034) and receiving phenytoin for an
      indication other than seizure (P=0.035), were associated with a greater
      likelihood of adequate concentrations. In conclusion, phenytoin dosing remains
      complex in critically ill patients, although lower per kilogram loading doses are
      strongly associated with free concentrations below the desired target. 

PMID- 23977912
TI  - Diagnostic potential of open lung biopsy in mechanically ventilated patients with
      diffuse pulmonary infiltrates of unclear aetiology.
AB  - Acute respiratory failure with bilateral pulmonary infiltrates is a clinical
      problem with a wide differential diagnosis. We evaluated whether open lung biopsy
      offered a diagnosis and therapeutic guidance in cases of unclear diagnosis after
      non-invasive tests. For this purpose, we reviewed 60 cases of open lung biopsy
      performed between 2002 and 2009 in patients with acute respiratory failure and
      bilateral infiltrates at the intensive care unit of Ghent University Hospital.
      Pathological diagnosis was classified as specific or non-specific and its
      contribution to therapy and decision-making was evaluated by a panel of three
      intensive care unit physicians. We found that a specific pathological diagnosis
      was present in 39 open lung biopsy patients (65%; 95% confidence interval 52 to
      76%): idiopathic interstitial pneumonia in 24 patients, malignancy in four
      patients, pulmonary infectious disease in nine patients, and a combination of
      specific diagnoses in two patients. Open lung biopsy contributed to patient
      management in 53 cases (88%) as it led to the initiation, modification or
      discontinuation of therapeutic drugs in 36, and contributed to the decision to
      continue or withdraw ventilator support in 17. Complications of open lung biopsy
      were noted in 14 patients (23%). We conclude that open lung biopsy was a useful
      diagnostic intervention in of a selected group of patients with acute respiratory
      failure and bilateral infiltrates of unclear clinical diagnosis, as it offered a
      specific diagnosis in 65%. 

PMID- 23977913
TI  - Binding of local anaesthetics to the lipid emulsion ClinoleicTM 20%.
AB  - Lipid emulsions have been used to treat cardiovascular collapse due to local
      anaesthetic toxicity. However, there are few data available on the comparative
      efficiency of the partitioning properties of available lipid emulsions in
      clinical use. This in vitro study compared the buffering properties of the lipid
      emulsions ClinoleicTM 20% (Baxter, Old Toongabbie, NSW) and Intralipid(r) 20%
      (Fresenius Kabi, Pymble, NSW) using both bupivacaine (Marcain(r) 0.5%,
      AstraZeneca, North Ryde, NSW) and ropivacaine (Naropin(r) 1%, AstraZeneca, North
      Ryde, NSW). The concentration of anaesthetic in buffer before and after mixing
      with lipid was quantified using chromatographic analysis. Bupivacaine was more
      effectively bound by the lipid agents, with a 40% reduction in initial
      concentration. Ropivacaine demonstrated a 20% reduction in concentration with the
      addition of lipid agents. Importantly, there was no significant difference
      between Intralipid and Clinoleic in terms of their buffering behaviour,
      suggesting equivalent binding efficacy.

PMID- 23977914
TI  - Training for cricothyroidotomy.
AB  - Cricothyroidotomy is infrequently performed in the intensive care unit but may be
      a lifesaving procedure. The aim of this study was to determine the number of
      attempts required by trainees to gain adequate skills for a successful
      cricothyroidotomy (defined as lung inflation <60 seconds). The effect of training
      on time to completion of cricothyroidotomy was also studied. After viewing a
      demonstration video on the procedure, each participant attempted
      cricothyroidotomy five times consecutively on a manikin with a pre-assembled
      Melker cricothyroidotomy kit. Time from 'skin' palpation to 'lung' inflation was
      recorded for 30 participants. Time to completion of cricothyroidotomy decreased
      over consecutive attempts within each participant (F4df=39.6; P <0.001) and
      between participant variability in times recorded at each attempt also decreased
      (P=0.04). Overall improvement in time to completion was seen even between the
      fourth and fifth attempts (mean difference -6.3 seconds; P <0.001). All
      participants were successful by the fifth attempt, by which stage all but two had
      been successful on two consecutive attempts. Age, years of postgraduate practice
      and level of seniority appeared to be associated with earlier success.
      Consecutive attempts on a manikin led to an improvement in the time to completion
      of cricothyroidotomy and rate of a successful outcome (<60 seconds). We recommend
      that clinicians undergo at least five training attempts on a manikin to gain
      proficiency in cricothyroidotomy. 

PMID- 23977915
TI  - Approaches to learning for the ANZCA Final Examination and validation of the
      revised Study Process Questionnaire in specialist medical training.
AB  - When evaluating assessments, the impact on learning is often overlooked.
      Approaches to learning can be deep, surface and strategic. To provide insights
      into exam quality, we investigated the learning approaches taken by trainees
      preparing for the Australian and New Zealand College of Anaesthetists (ANZCA)
      Final Exam. The revised two-factor Study Process Questionnaire (R-SPQ-2F) was
      modified and validated for this context and was administered to ANZCA advanced
      trainees. Additional questions were asked about perceived value for anaesthetic
      practice, study time and approaches to learning for each exam component. Overall,
      236 of 690 trainees responded (34%). Responses indicated both deep and surface
      approaches to learning with a clear preponderance of deep approaches. The
      anaesthetic viva was valued most highly and the multiple choice question
      component the least. Despite this, respondents spent the most time studying for
      the multiple choice questions. The traditionally low short answer questions pass
      rate could not be explained by limited study time, perceived lack of value or
      study approaches. Written responses suggested that preparation for multiple
      choice questions was characterised by a surface approach, with rote memorisation
      of past questions. Minimal reference was made to the ANZCA syllabus as a guide
      for learning. These findings indicate that, although trainees found the exam
      generally relevant to practice and adopted predominantly deep learning
      approaches, there was considerable variation between the four components. These
      results provide data with which to review the existing ANZCA Final Exam and
      comparative data for future studies of the revisions to the ANZCA curriculum and
      exam process.

PMID- 23977916
TI  - Mental health and welfare in Australian anaesthetists.
AB  - This survey was designed to evaluate the factors affecting mental health and
      welfare in Australian anaesthetists and to investigate current sources of
      support. An electronic survey was sent to 500 randomly selected Fellows and
      trainees of the Australian and New Zealand College of Anaesthetists. Questions
      were related to: anxiety, stress, depression, substance misuse, self-medication,
      suicide, reporting illness, and help-seeking. Current psychological wellbeing was
      assessed using the Kessler Psychological Distress Scale (K10). A total of 191
      completed surveys were received (a response rate of 38%): 26% had attended their
      general practitioner for mental health issues, of whom half had been diagnosed
      with a mental illness; 7% of all respondents were currently prescribed medication
      for this; 25% had previously self-prescribed psychoactive medication; 17%
      admitted to using alcohol to deal with stress, anxiety or depression; and 8%
      responded that mental illness had at some point impaired clinical care. Sixteen
      percent of all respondents reported previous suicidal ideation. Despite a low
      response rate, and the possibility of responder bias, the mental health of
      Australian anaesthetists would appear to be subject to common and persistent risk
      factors, many of which are well described in previous studies. We identify
      general practitioners as particularly valuable in targeting initiatives for
      improvements in mental health and welfare. The significant prevalence of suicidal
      ideation and reluctance to approach senior colleagues with concerns about mental
      health or welfare issues are specific causes for concern and suggest that further
      investigation, education and a potential review of support networks is required. 

PMID- 23977917
TI  - Home blood pressure monitoring in an anaesthetic pre-admission clinic.
AB  - We suspected that many high blood pressure measurements taken in our anaesthetic
      pre-assessment clinic and immediately prior to induction of anaesthesia were
      unusually elevated due to a 'white coat' effect. These high blood pressure
      measurements were causing late cancellations of surgery, even though white coat
      measurements may not be representative of the patient's usual blood pressure or
      of their risk of end-organ damage due to hypertension. In this audit, patients
      with high blood pressure in our pre-admission clinic were provided with training
      and a home blood pressure monitor to use prior to surgery. These were compared to
      the pre-admission clinic measurements to determine the incidence of white coat
      hypertension. We also compared home to general practice blood pressure monitoring
      where possible. Fifty-two patients were provided with monitors. Fifty-one of
      these took at least five measurements at home. Thirty-four (66%) patients had
      average measurements at home at least 20 mmHg lower than pre-admission clinic
      measurements. A total of 33% of general practice clinic measurements were also >=
      20 mmHg higher than average home measurements. White coat hypertension was common
      in our audit population. Relying on average home blood pressure measurements
      rather than 'one off' in-hospital measurements may have helped to prevent the
      postponement or cancellation of surgery for 13 patients who had recorded blood
      pressure >= 180/110 mmHg in our pre-admission clinic.

PMID- 23977918
TI  - Pioneering paediatric intensive care medicine in New Zealand.
AB  - The origin of New Zealand's paediatric intensive care medicine lay in the formal
      establishment of Auckland Hospital's Central Respiratory Unit within the
      hospital's Infectious Diseases Unit (December 1958). It was initially established
      for the care of critically ill children, chiefly with airway and respiratory
      disorders or tetanus. Senior Specialist Anaesthetist Matthew Spence soon took
      charge, his first annual report (1960) briefly describing six children among 19
      admissions and another six consulted on elsewhere. Rapid build-up of paediatric
      admissions-36 in 1963 becoming 104 in 1969-is detailed through Dr Spence's
      admirable annual reports for that period, which also provide the evidence of his
      organisational brilliance and personal commitment to development of the unit.
      Treatment for children, approximately a third of all admissions, soon included
      management of brain swelling from meningitis, intractable convulsions, traumatic
      brain injury, etc. Critically ill children were occasionally flown into Auckland;
      others were cared for regionally as further intensive care units developed
      throughout New Zealand. Successive additions to medical staffing gradually
      resulted in four full-time intensivists after Dr Spence's retirement in 1983. Dr
      James Judson computerised record-keeping from 1984 and developed a large
      database, containing details of children with numbers approaching 2000. At the
      end of 1991, the (now) Department of Critical Care Medicine completed its
      paediatric role over three decades, with care of children passing to a paediatric
      intensive care unit in the new Auckland paediatric hospital (soon to be called
      "Starship"). Regional intensive care units still make a substantial contribution
      to paediatric intensive care countrywide. 

PMID- 23977919
TI  - Nerve sheath catheter analgesia for forequarter amputation in paediatric oncology
      patients.
AB  - In a single centre over two years, four children (7 to 10 years old) with upper
      limb osteosarcoma underwent chemotherapy followed by forequarter amputation. All
      patients had preoperative pain and were treated with gabapentin. Nerve sheath
      catheters were placed in the brachial plexus intraoperatively and left in situ
      for five to 14 days. After surgery, all patients received local anaesthetic
      infused via nerve sheath catheters as part of a multimodal analgesia technique.
      Three of the four patients were successfully treated as outpatients with the
      nerve sheath catheters in situ. All four children experienced phantom limb pain;
      however, it did not persist beyond four weeks in any patient. 

PMID- 23977920
TI  - Patient recollections of perioperative anaesthesia risks.

PMID- 23977921
TI  - Postgraduate specialty training in private institutions and anaesthesia training
      in a private healthcare facility.

PMID- 23977922
TI  - Future trials to investigate a ward physician leadership model for the Medical
      Emergency Team are not logistically feasible.

PMID- 23977923
TI  - Airway management of an expanding soft palate haematoma in a parturient.

PMID- 23977924
TI  - Absent expiratory valve missed by automated check in Drager Primus anaesthesia
      workstation.

PMID- 23977925
TI  - Vasopressor for hypothyroid patients--is phenylephrine the right choice?

PMID- 23977926
TI  - A technique for safe endotracheal tube exchange in difficult airway patients.

PMID- 23977927
TI  - Geotrichum capitatum fungaemia: an unusual pathogen in critically-ill-related
      infections.

PMID- 23977928
TI  - Unilateral plication following phrenic nerve transection and failure to wean from
      mechanical ventilation.

PMID- 23977929
TI  - Arterial injection of adrenaline causing severe hypertension during emergency
      gastroscopy.

PMID- 23977930
TI  - The pitfalls of anatomical abnormality in central line insertion in the ICU.

PMID- 23977931
TI  - How further suppression of virus replication could improve current HBV treatment.

PMID- 23977933
TI  - Fidaxomicin: a minimally absorbed macrocyclic antibiotic for the treatment of
      Clostridium difficile infections.
AB  - Fidaxomicin was approved for the treatment of Clostridium difficile infections in
      2011. It has a novel mechanism of action and narrow spectrum of activity that
      makes it unique among the currently used therapies for this disease. Phase III
      clinical studies demonstrated a benefit of fidaxomicin over vancomycin for the
      outcomes of recurrence and global cure or sustained clinical response. This
      observation was confirmed within specific populations, including those of older
      age, immunocompromised due to active cancers, and patients taking concomitant
      antibiotics. Additionally, fidaxomicin significantly reduced recurrence rates
      compared to vancomycin among patients receiving treatment for recurrent C.
      difficile episodes. Fidaxomicin represents an advance in therapy for the
      treatment of C. difficile infections. 

PMID- 23977934
TI  - Streptococcus pneumoniae infection: a Canadian perspective.
AB  - Streptococcus pneumoniae infections have resulted in significant morbidity and
      mortality worldwide in children and adults. In Canada, Streptococcus pneumoniae
      remains one of the leading causes of infectious disease including pneumonia,
      meningitis, bacteremia and otitis media. Although the widespread use of
      pneumococcal conjugate vaccines (PCVs) in Canadian children has reduced the
      incidence of pneumococcal diseases associated with vaccine-serotypes, rapid
      increase of non-vaccine serotypes in carriage and pneumococcal infections is of
      great concern to clinicians. The main goal of this review is to provide an
      overall picture of invasive pneumococcal diseases (IPD) in Canada for the past
      few decades, including serotype changes and shifts in antibiotic resistance
      patterns. The effects of PCV vaccines on incidence, serotype distribution,
      antibiotic resistance of pneumococcal infections and nasopharyngeal (NP) carriage
      are discussed. We also examined historical outbreaks of Streptococcus pneumoniae
      and their public health impact. Recent developments in universal protein vaccines
      against pneumococcus show promise. 

PMID- 23977935
TI  - Application of West Nile virus diagnostic techniques.
AB  - West Nile virus (WNV) is an enveloped RNA virus in the family Flaviviridae and
      belongs to Japanese encephalitis virus serocomplex group. The WNV has a wide
      geographic distribution that includes Africa, Europe, Asia, America and
      Australia. Recently, it has re-emerged as an important pathogenic organism,
      illustrated by the series of WNV outbreaks in North America and in Europe.
      Several hundred people are sacrificed by WNV infection every year. WNV can infect
      many mammals, birds, reptiles and amphibians. A variety of diagnoses for WNV
      infection have been developed, such as virus isolation, nucleotide amplification,
      antigen detection and serology. Flaviviruses, including WNV, share common
      nucleotide sequences and antigenic epitopes. Understanding these properties that
      can influence cross-reactivity is important for accurate diagnosis, especially
      because areas with multiple flaviviruses are currently expanding. Herein, the
      authors outline the different diagnostic methods for detecting WNV infection as
      well as important considerations in using these methods. 

PMID- 23977936
TI  - The management and the diagnosis of fever of unknown origin.
AB  - Prolonged fever presents a challenge for the patient and the physician. Fever
      with a temperature higher than 38.3 degrees C on several occasions that lasts for
      at least 3 weeks and lacks a clear diagnosis after 1 week of study in the
      hospital is called a fever of unknown origin (FUO). More than 200 diseases can
      cause FUO, and the information gathered from history taking, physical
      examination, laboratory and imaging studies should be evaluated with care.
      History taking and physical examination may provide some localizing signs and
      symptoms pointing toward a diagnosis. Infection, cancers, noninfectious
      inflammatory diseases and some miscellaneous diseases are the main etiologies,
      and some patients remain undiagnosed despite investigations. Tuberculosis,
      lymphoma and adult-onset Still's disease are the main diseases.
      Fluorodeoxyglucose PET is a promising imaging modality in FUO. Establishing a
      uniform algorithm for FUO management is difficult. Every patient should be
      carefully evaluated individually considering the previous FUO management
      experience. 

PMID- 23977937
TI  - Prophylaxis and therapy of plague.
AB  - Plague has been a scourge of mankind for centuries, and outbreaks continue to the
      present day. The virulence mechanisms employed by the etiological agent Yersinia
      pestis are reviewed in the context of the available prophylactic and therapeutic
      strategies for plague. Although antibiotics are available, resistance is emerging
      in this dangerous pathogen. Therapeutics used in the clinic are discussed and
      innovative approaches to the design and development of new therapeutic compounds
      are reviewed. Currently there is no licensed vaccine available for prevention of
      plague in the USA or western Europe, although both live attenuated strains and
      killed whole-cell extracts have been used historically. Live strains are still
      approved for human use in some parts of the world, such as the former Soviet
      Union, but poor safety profiles render them unacceptable to many countries. The
      development of safe, effective next-generation vaccines, including the
      recombinant subunit vaccine currently used in clinical trials is discussed. 

PMID- 23977938
TI  - Pseudomonas aeruginosa treatment and transmission reduction.
AB  - Infections caused by Pseudomonas aeruginosa can be difficult to treat and require
      a coordinated approach for their management. This involves quickly controlling
      the source of infection, establishing a correct etiologic diagnosis and
      administering appropriate empiric antimicrobial therapy. Once antimicrobial
      therapy has been initiated and susceptibilities are available, therapy should be
      tailored with optimized antibiotic doses for an appropriate duration in order to
      sufficiently treat the infection and minimize resistance emergence. 

PMID- 23977939
TI  - Clinical management of early syphilis.
AB  - Early syphilis therapy was a focus of intense research in the early 20th century
      with many and varied approaches being used. The development of penicillin and its
      efficacy in the treatment of syphilis transformed syphilis management for many
      with and at risk for infection. However, problems such as beta-lactam allergies
      and the desire for easily administered, alternate therapies have led to
      evaluation of multiple other drugs, with doxycycline currently recommended as the
      main alternative. Ceftriaxone and azithromycin have been shown to be effective,
      however, each has its own difficulties. Follow-up relies on serological testing,
      leading to concerns when these tests do not decline appropriately. Given concerns
      about the potential for increased risk for treatment failure, patients with HIV
      and pregnant women are of particular concern. 

PMID- 23977942
TI  - Comparison of effects of lower extremity orthoses on energy expenditure in
      patients with cerebral palsy.
AB  - OBJECTIVE: The aim of the study was to compare the effects of lower extremity
      orthoses on energy expenditure in patients with cerebral palsy (CP). METHODS: We
      included 48 children with CP using lower extremity orthosis. Energy expenditures
      determined based on heart rate, yielded an energy expenditure index (EEI) with
      and without orthosis during walking. RESULTS were compared statistically between
      orthosis groups (solid polyethylene ankle foot orthosis (PAFO), articulated PAFO,
      ground reaction foot orthosis (GRAFO), plastic and metallic knee-ankle-foot
      orthosis (KAFO), and metallic AFO). RESULTS: It was found that an advancement in
      energy expenditure was seen with plastic orthoses which is more prominent by
      solid PAFO (p = 0.008). CONCLUSION: It was concluded that especially solid PAFO
      can be more beneficial in terms of energy consumption in CP patients. In
      rehabilitation phase, the EEI measurement was seen to be a useful and practical
      method for choosing the proper orthosis type.

PMID- 23977941
TI  - Vitamin B6 reduces hippocampal apoptosis in experimental pneumococcal meningitis.
AB  - BACKGROUND: Bacterial meningitis caused by Streptococcus pneumoniae leads to
      death in up to 30% of patients and leaves up to half of the survivors with
      neurological sequelae. The inflammatory host reaction initiates the induction of
      the kynurenine pathway and contributes to hippocampal apoptosis, a form of brain
      damage that is associated with learning and memory deficits in experimental
      paradigms. Vitamin B6 is an enzymatic cofactor in the kynurenine pathway and may
      thus limit the accumulation of neurotoxic metabolites and preserve the cellular
      energy status. The aim of this study in a pneumococcal meningitis model was to
      investigate the effect of vitamin B6 on hippocampal apoptosis by histomorphology,
      by transcriptomics and by measurement of cellular nicotine amide adenine
      dinucleotide content. METHODS AND RESULTS: Eleven day old Wistar rats were
      infected with 1x10(6) cfu/ml of S. pneumoniae and randomized for treatment with
      vitamin B6 or saline as controls. Vitamin B6 led to a significant (p > 0.02)
      reduction of hippocampal apoptosis. According to functional annotation based
      clustering, vitamin B6 led to down-regulation of genes involved in processes of
      inflammatory response, while genes encoding for processes related to circadian
      rhythm, neuronal signaling and apoptotic cell death were mostly up-regulated.
      CONCLUSIONS: Our results provide evidence that attenuation of apoptosis by
      vitamin B6 is multi-factorial including down-modulation of inflammation, up
      regulation of the neuroprotective brain-derived neurotrophic factor and
      prevention of the exhaustion of cellular energy stores. The neuroprotective
      effect identifies vitamin B6 as a potential target for the development of
      strategies to attenuate brain injury in bacterial meningitis.

PMID- 23977943
TI  - Three-dimensional plasmonic nanoclusters.
AB  - Assembling nanoparticles into well-defined structures is an important way to
      create and tailor the optical properties of materials. Most advances in
      metamaterials research to date have been based on structures fabricated in two
      dimensional planar geometries. Here, we show an efficient method for assembling
      noble metal nanoparticles into stable, three-dimensional (3-D) clusters, whose
      optical properties can be highly sensitive or remarkably independent of cluster
      orientation, depending on particle number and cluster geometry. Some of the
      clusters, such as tetrahedra and icosahedra, could serve as the optical kernels
      for metafluids, imparting metamaterial optical properties into disordered media
      such as liquids, glasses, or plastics, free from the requirement of nanostructure
      orientation. 

PMID- 23977944
TI  - Increasing the metabolic capacity of Escherichia coli for hydrogen production
      through heterologous expression of the Ralstonia eutropha SH operon.
AB  - BACKGROUND: Fermentative hydrogen production is an attractive means for the
      sustainable production of this future energy carrier but is hampered by low
      yields. One possible solution is to create, using metabolic engineering, strains
      which can bypass the normal metabolic limits to substrate conversion to hydrogen.
      Escherichia coli can degrade a variety of sugars to hydrogen but can only convert
      electrons available at the pyruvate node to hydrogen, and is unable to use the
      electrons available in NADH generated during glycolysis. RESULTS: Here, the
      heterologous expression of the soluble [NiFe] hydrogenase from Ralstonia eutropha
      H16 (the SH hydrogenase) was used to demonstrate the introduction of a pathway
      capable of deriving substantial hydrogen from the NADH generated by fermentation.
      Successful expression was demonstrated by in vitro assay of enzyme activity.
      Moreover, expression of SH restored anaerobic growth on glucose to adhE strains,
      normally blocked for growth due to the inability to re-oxidize NADH. Measurement
      of in vivo hydrogen production showed that several metabolically engineered
      strains were capable of using the SH hydrogenase to derive 2 mol H2 per mol of
      glucose consumed, close to the theoretical maximum. CONCLUSION: Previous
      introduction of heterologous [NiFe] hydrogenase in E. coli led to NAD(P)H
      dependent activity, but hydrogen production levels were very low. Here we have
      shown for the first time substantial in vivo hydrogen production by a
      heterologously expressed [NiFe] hydrogenase, the soluble NAD-dependent H2ase of
      R. eutropha (SH hydrogenase). This hydrogenase was able to couple metabolically
      generated NADH to hydrogen production, thus rescuing an alcohol dehydrogenase
      (adhE) mutant. This enlarges the range of metabolism available for hydrogen
      production, thus potentially opening the door to the creation of greatly improved
      hydrogen production. Strategies for further increasing yields should revolve
      around making additional NADH available.

PMID- 23977945
TI  - Binding of a structured D-RNA molecule by an L-RNA aptamer.
AB  - An L-RNA aptamer was developed that binds the natural D-form of the HIV-1 trans
      activation responsive (TAR) RNA. The aptamer initially was obtained as a D
      aptamer against L-TAR RNA through in vitro selection. Then the corresponding L
      aptamer was prepared by chemical synthesis and used to bind the desired target.
      The L-aptamer binds D-TAR RNA with a Kd of 100 nM. It binds D-TAR exclusively at
      the six-nucleotide distal loop, but does so through tertiary interactions rather
      than simple Watson-Crick pairing. This complex is the first example of two
      nucleic acids molecules of opposing chirality that interact through a mode of
      binding other than primary structure. Binding of the L-aptamer to D-TAR RNA
      inhibits formation of the Tat-TAR ribonucleoprotein complex that is essential for
      TAR function. This suggests that L-aptamers, which are intrinsically resistant to
      degradation by ribonucleases, might be pursued as an alternative to antisense
      oligonucleotides to target structured RNAs of biological or therapeutic interest.

PMID- 23977946
TI  - Spread of Kyasanur Forest disease, Bandipur Tiger Reserve, India, 2012-2013.

PMID- 23977947
TI  - External control of the Drosophila melanogaster lifespan by combination of 3D
      oscillating low-frequency electric and magnetic fields.
AB  - We demonstrate that the lifespan of Drosophila melanogaster population is
      controllable by a combination of external three-dimensional oscillating low
      frequency electric and magnetic fields (3D OLFEMFs). The lifespan was decreased
      or increased in dependence of the parameters of the external 3D OLFEMFs. We
      propose that metabolic processes in D. melanogaster's body are either accelerated
      (in the case of reduced lifespan) or slowed down (in the case of increased
      lifespan) in function of 3D OLFEMFs that induce vibrational motions on sub
      cellular and larger scales.

PMID- 23977948
TI  - Preparation of three-dimensional graphene oxide-polyethylenimine porous materials
      as dye and gas adsorbents.
AB  - We report a facile method for the fabrication of three-dimensional (3D) porous
      materials via the interaction between graphene oxide (GO) sheets and
      polyethylenimine (PEI) with high amine density at room temperature under
      atmospheric pressure without stirring. The structural and physical properties of
      GO-PEI porous materials (GEPMs) are investigated by scanning electron microscopy,
      X-ray diffraction, thermogravimetric analysis, and nitrogen adsorption-desorption
      measurement and their chemical properties are analyzed by X-ray photoelectron
      spectroscopy, infrared spectroscopy, and Raman spectroscopy. GEPMs possess low
      density and hierarchical morphology with large specific surface area, and big
      pore volume. Furthermore, the as-prepared 3D porous materials show an excellent
      adsorption capacity for acidic dyes on the basis of the pore-rich and amine-rich
      graphene structure. GEPMs exhibit an extremely high adsorption capacity for
      amaranth (800 mg g(-1)), which are superior to other carbon materials. In
      addition, GEPMs also exhibit good adsorption capacity for carbon dioxide (11.2 wt
      % at 1.0 bar and 273 K). 

PMID- 23977950
TI  - Solvation effects on self-association and segregation processes in tert-butanol
      aprotic solvent binary mixtures.
AB  - The present study reveals that the fully miscible binary mixtures consisting of
      tert-butanol with aprotic solvents form well-defined ordered supermolecular
      structures, which have been characterized on different length scales. Three
      different types of microstructures have been determined. They are separated by
      distinct crossovers that appear as a function of the dilution rate, going from
      "correlated clusters" to "diluted clusters" and "diluted monomer"
      microstructures. These observations have been made possible by the combination of
      Raman vibration spectroscopy, (1)H NMR, and neutron diffraction that probe,
      respectively, the cluster formation (self-association) and the intercluster
      correlations (cluster segregation). The solvation effects on both the cluster
      formation and the intercluster correlations have been assessed by tuning the
      alcohol-solvent interaction, i.e., changing the chemical nature of the diluting
      solvent from a purely inert alkane to a weakly interacting aromatic system. 

PMID- 23977951
TI  - Translator's preface.
AB  - Presents a preface from James T. Lamiell, who translates Wilhelm Wundt's
      Psychology's Struggle for Existence (Die Psychologie im Kampf ums Dasein), in
      which Wundt advised against the impending divorce of psychology from philosophy,
      into English. Lamiell comments that more than a decade into the 21st century, it
      appears that very few psychologists have any interest at all in work at the
      interface of psychology and philosophy. He notes that one clear indication of
      this is that the Society for Theoretical and Philosophical Psychology, which is
      Division 24 of the American Psychological Association (APA), remains one of the
      smallest of the APA's nearly 60 divisions. (PsycINFO Database Record (c) 2013
      APA, all rights reserved). 

PMID- 23977949
TI  - Tunable and multifunctional eukaryotic transcription factors based on CRISPR/Cas.
AB  - Transcriptional regulation is central to the complex behavior of natural
      biological systems and synthetic gene circuits. Platforms for the scalable,
      tunable, and simple modulation of transcription would enable new abilities to
      study natural systems and implement artificial capabilities in living cells.
      Previous approaches to synthetic transcriptional regulation have relied on
      engineering DNA-binding proteins, which necessitate multistep processes for
      construction and optimization of function. Here, we show that the CRISPR/Cas
      system of Streptococcus pyogenes can be programmed to direct both activation and
      repression to natural and artificial eukaryotic promoters through the simple
      engineering of guide RNAs with base-pairing complementarity to target DNA sites.
      We demonstrate that the activity of CRISPR-based transcription factors
      (crisprTFs) can be tuned by directing multiple crisprTFs to different positions
      in natural promoters and by arraying multiple crisprTF-binding sites in the
      context of synthetic promoters in yeast and human cells. Furthermore, externally
      controllable regulatory modules can be engineered by layering gRNAs with small
      molecule-responsive proteins. Additionally, single nucleotide substitutions
      within promoters are sufficient to render them orthogonal with respect to the
      same gRNA-guided crisprTF. We envision that CRISPR-based eukaryotic gene
      regulation will enable the facile construction of scalable synthetic gene
      circuits and open up new approaches for mapping natural gene networks and their
      effects on complex cellular phenotypes. 

PMID- 23977952
TI  - Psychology's struggle for existence: Second edition, 1913.
AB  - Presents an English translation of Wilhelm Wundt's Psychology's struggle for
      existence: Second edition, 1913, by James T. Lamiell in August, 2012. In his
      essay, Wundt advised against the impending divorce of psychology from philosophy.
      (PsycINFO Database Record (c) 2013 APA, all rights reserved). 

PMID- 23977953
TI  - The Wilhelm Wundt Center and the first graduate program for the history and
      philosophy of psychology in Brazil: A brief report.
AB  - The expansion of Brazilian universities since 2009 has promoted a general growth
      and incentive of scientific activities throughout the country, not only in the so
      called hard sciences, but also in the human sciences. In this brief report, we
      announce the creation of two new institutional spaces dedicated to the history
      and philosophy of psychology at the Federal University of Juiz de Fora (UFJF) in
      Brazil: the Wilhelm Wundt Center for the History and Philosophy of Psychology
      (NUHFIP) and the Graduate Program in History and Philosophy of Psychology.
      (PsycINFO Database Record (c) 2013 APA, all rights reserved). 

PMID- 23977955
TI  - Total syntheses of the coumarin-containing natural products pimpinellin and
      fraxetin using Au(I)-catalyzed intramolecular hydroarylation (IMHA) chemistry.
AB  - The title natural products (1 and 2, respectively) have been synthesized by Au(I)
      catalyzed intramolecular hydroarylation (IMHA) of the relevant aryl propiolate
      esters (e.g., 13), which were themselves formed by reaction of the corresponding
      phenols with either 3-(trimethylsilyl)propiolic acid or propiolic acid and N-(3
      dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride or
      dicyclohexylcarbodiimide. (+/-)-Purpurasol (3) was readily derived from fraxetin
      (2) by established procedures. 

PMID- 23977956
TI  - Preparative chromatography for obtaining pure samples of rosaniline, magenta II,
      and new fuchsine.
AB  - A simple low pressure liquid chromatographic method is reported that can separate
      the basic fuchsine homologues, rosaniline, magenta II and new fuchsine from an
      impure commercial dye. The chromatographic purity of the separated dyes is > 90%.
      All homologues were obtained in multi-milligram amounts per chromatographic run;
      precise yields depend on the composition of the starting material and potentially
      may be greater. This is a useful preparative procedure for generating
      chromatographically pure samples of basic fuchsine homologues, especially those
      that cannot be obtained in pure form by direct synthesis.

PMID- 23977957
TI  - Effects of prenatal exposure to diclofenac sodium and saline on the optic nerve
      of 4- and 20-week-old male rats: a stereological and histological study.
AB  - We investigated the effects of diclofenac sodium (DS) on development of the optic
      nerve in utero. Pregnant female rats were separated into three groups: control,
      saline treated and DS treated. Offspring of these animals were divided into 4
      week-old and 20-week-old groups. At the end of the 4th and 20th weeks of
      postnatal life, the animals were sacrificed, and right optic nerves were excised
      and sectioned for ultrastructural and stereological analyses. We demonstrated
      that both DS and saline produced structural and morphometric changes in the total
      axon number and density of axons, but decreased the myelin sheath thickness in
      male optic nerves. All ultrastructural and morphometric features were well
      developed in 20-week-old rats. We showed that development of the optic nerve
      continues during the early postnatal period and that some compensation for
      exposure to deleterious agents in utero may occur during early postnatal life.

PMID- 23977958
TI  - Syntheses and characterizations of linear triborazanes.
AB  - Reaction of the amine boranes NH2(R)BH3, where R = H, Me, and Bz, with 1/3 equiv
      of sodium hexamethyldisilazane produced the five-membered, linear aminoborane
      anions Na(+)[BH3N(R)HBH2N(R)HBH3(-)], where R = H (1), Me (1Me), and benzyl
      (1Bz). Reactions of 1 and 1Me with ammonium chloride and methylammonium chloride,
      respectively, resulted in elimination of NaCl and H2 to produce the linear
      triborazanes BH3(RNHBH2)2N(R)H2, where R = H (2) and Me (2Me), with the structure
      of 2 crystallographically confirmed. The reactions of 1 and 1Me with pyridine-HCl
      produced the pyridine-capped aminoboranes H3B(RNHBH2)2(NC5H5), where R = H (3)
      and Me (3Me). 2 and 2Me proved to be stable up to 90  degrees C but produced a
      mixture of products when heated above 90  degrees C. 2 was selectively
      monochlorinated at the terminal boron when treated with 1 equiv of HCl and
      dichlorinated when reacted with a second 1 equiv of HCl.

PMID- 23977960
TI  - Cloning, characterization, and inhibition studies of a beta-carbonic anhydrase
      from Leishmania donovani chagasi, the protozoan parasite responsible for
      leishmaniasis.
AB  - Leishmaniasis is an infection provoked by protozoans belonging to the genus
      Leishmania. Among the many species and subsepecies of such protozoa, Leishmania
      donovani chagasi causes visceral leishmaniasis. A beta-carbonic anhydrase (CA, EC
      4.2.1.1) was cloned and characterized from this organism, denominated here LdcCA.
      LdcCA possesses effective catalytic activity for the CO2 hydration reaction, with
      kcat of 9.35 * 10(5) s(-1) and kcat/KM of 5.9 * 10(7) M(-1) s(-1). A large number
      of aromatic/heterocyclic sulfonamides and 5-mercapto-1,3,4-thiadiazoles were
      investigated as LdcCA inhibitors. The sulfonamides were medium potency to weak
      inhibitors (KI values of 50.2 nM-9.25 MUM), whereas some heterocyclic thiols
      inhibited the enzyme with KIs in the range of 13.4-152 nM. Some of the
      investigated thiols efficiently inhibited the in vivo growth of Leishmania
      chagasi and Leishmania amazonensis promastigotes, by impairing the flagellar
      pocket and movement of the parasites and causing their death. The beta-CA from
      Leishmania spp. is proposed here as a new antileishmanial drug target.

PMID- 23977959
TI  - Characterizing the promiscuity of LigAB, a lignin catabolite degrading extradiol
      dioxygenase from Sphingomonas paucimobilis SYK-6.
AB  - LigAB from Sphingomonas paucimobilis SYK-6 is the only structurally characterized
      dioxygenase of the largely uncharacterized superfamily of Type II extradiol
      dioxygenases (EDO). This enzyme catalyzes the oxidative ring-opening of
      protocatechuate (3,4-dihydroxybenzoic acid or PCA) in a pathway allowing the
      degradation of lignin derived aromatic compounds (LDACs). LigAB has also been
      shown to utilize two other LDACs from the same metabolic pathway as substrates,
      gallate, and 3-O-methyl gallate; however, kcat/KM had not been reported for any
      of these compounds. In order to assess the catalytic efficiency and get insights
      into the observed promiscuity of this enzyme, steady-state kinetic analyses were
      performed for LigAB with these and a library of related compounds. The
      dioxygenation of PCA by LigAB was highly efficient, with a kcat of 51 s(-1) and a
      kcat/KM of 4.26 * 10(6) M(-1)s(-1). LigAB demonstrated the ability to use a
      variety of catecholic molecules as substrates beyond the previously identified
      gallate and 3-O-methyl gallate, including 3,4-dihydroxybenzamide,
      homoprotocatechuate, catechol, and 3,4-dihydroxybenzonitrile. Interestingly, 3,4
      dihydroxybenzamide (DHBAm) behaves in a manner similar to that of the preferred
      benzoic acid substrates, with a kcat/Km value only ~4-fold lower than that for
      gallate and ~10-fold higher than that for 3-O-methyl gallate. All of these most
      active substrates demonstrate mechanistic inactivation of LigAB. Additionally,
      DHBAm exhibits potent product inhibition that leads to an inactive enzyme, being
      more highly deactivating at lower substrate concentration, a phenomena that, to
      our knowledge, has not been reported for another dioxygenase substrate/product
      pair. These results provide valuable catalytic insight into the reactions
      catalyzed by LigAB and make it the first Type II EDO that is fully characterized
      both structurally and kinetically.

PMID- 23977961
TI  - Soy protein nanoparticle aggregates as pickering stabilizers for oil-in-water
      emulsions.
AB  - In recent years, there have been increasing interests in developing food-grade
      Pickering stabilizers, due to their potential applications in formulations of
      novel functional foods. The present work was to investigate the potential of soy
      proteins to be developed into a kind of Pickering-like stabilizer for oil-in
      water emulsions. The nanoparticle aggregates of soy protein isolate (SPI) were
      formed by sequential treatments of heating at 95  degrees C for 15 min and then
      electrostatic screening with NaCl addition. The particle size and microstructure
      of these aggregates were characterized using dynamic light scattering and atomic
      force microscopy, indicating that the fabricated nanoparticle aggregates were
      ~100 nm in size with more surface hydrophobic nature (relative to unheated SPI).
      The influence of particle concentration (c; 0.5-6.0%, w/w) and increasing oil
      fraction (phi; in the range 0.2-0.6) on the droplet size and coalescence and/or
      creaming stability of the emulsions stabilized by these nanoparticle aggregates
      was investigated. The results showed that, at phi = 0.2, increasing the c
      resulted in a progressive but slight decrease in droplet size, and improved the
      stability against coalescence and creaming; at a specific c, the creaming
      stability was progressively increased by increasing the phi, with better
      improvement observed at a higher c (e.g., 6.0% vs 2.0%). The improvement of
      creaming stability was largely associated with the formation of a gel-like
      network that could entrap the oil droplets within the network. The observations
      are generally consistent with those observed for the conventional Pickering
      emulsions, confirming that soy proteins could be applied as a kind of effective
      Pickering-like stabilizer. The finding may have important implications for the
      design and fabrication of protein-based emulsion formulations, and even for the
      development of soy protein products with some unique functions. To the authors'
      knowledge, this is the first work to report that heat-induced soy protein
      aggregates exhibit a good potential to act as Pickering-type stabilizers. 

PMID- 23977962
TI  - ACS Nano Lecture Award winners for 2013.

PMID- 23977966
TI  - Excluded volume model for the reduction of polymer diffusion into nanocomposites.
AB  - An analytic model for the slowing down of polymer chain diffusion in
      nanocomposites attributable to excluded volume effects is presented. The
      nanocomposite is modeled as an ensemble of cylinders through which the polymer
      chains diffuse. The reduction of polymer diffusion in each cylinder is equated
      with the reduction of diffusion for a sphere through a cylinder. The distribution
      of cylinder diameters within the ensemble is determined from statistical
      mechanical theories based on the packing of spherical particles. For low loadings
      of spherical particles in nanocomposites, this model results in a master curve
      for the reduced diffusion coefficient. With no adjustable parameters, the model
      agrees with recent data for tracer diffusion measurements in polymer
      nanocomposites at low loading. 

PMID- 23977967
TI  - Values and evidence colliding: health technology assessment in child health.

PMID- 23977965
TI  - High levels of IgG3 anti ICB2-5 in Plasmodium vivax-infected individuals who did
      not develop symptoms.
AB  - BACKGROUND: Plasmodium vivax has the potential to infect 2.85 billion individuals
      worldwide. Nevertheless, the limited number of studies investigating the immune
      status of individuals living in malaria-endemic areas, as well as the lack of
      reports investigating serological markers associated with clinical protection,
      has hampered development of vaccines for P. vivax. It was previously demonstrated
      that naturally total IgG against the N-terminus of P. vivax merozoite surface
      protein 1 (Pv-MSP1) was associated with reduced risk of malarial infection.
      METHODS: Immune response against Pv-MSP1 (N-terminus) of 313 residents of the Rio
      Pardo rural settlement (Amazonas State, Brazil) was evaluated in a cross
      sectional and longitudinal follow up over two months (on site) wherein gold
      standard diagnosis by thick blood smear and rRNA gene-based nested real-time PCR
      were used to discriminate symptomless Plasmodium vivax-infected individuals who
      did not develop clinical symptoms during a 2-months from those uninfected ones or
      who have had acute malaria. The acquisition of antibodies against Pv-MSP1 was
      also evaluated as survival analysis by prospective study over a year collecting
      information of new malaria infections in surveillance database. RESULTS: The
      majority of P. vivax-infected individuals (52-67%) showed immune recognition of
      the N-terminus of Pv-MSP1. Interesting data on infected individuals who have not
      developed symptoms, total IgG levels against the N-terminus Pv-MSP1 were age
      dependent and the IgG3 levels were significantly higher than levels of subjects
      had acute malaria or those uninfected ones. The total IgG anti ICB2-5 was
      detected to be an important factor of protection against new malaria vivax
      attacks in survival analysis in a prospective survey (p = 0.029). CONCLUSIONS:
      The study findings illustrate the importance of IgG3 associated to 2-months of
      symptomless in P. vivax infected individuals and open perspectives for the
      rationale of malaria vaccine designs capable to sustain high levels of IgG3
      against polymorphic malaria antigens.

PMID- 23977968
TI  - Phenotype/endotype-driven therapy in COPD: potential economic implications.

PMID- 23977969
TI  - Using health-related quality of life and quality-adjusted life expectancy for
      effective public health surveillance and prevention.

PMID- 23977971
TI  - The impact of the economic downturn on healthcare in Spain: consequences and
      alternatives.
AB  - In Spain, the economic downturn has caused big changes in most of the public
      policies, where healthcare system is the one which is deeply affected too. The
      objective of the paper is to review some of the recent changes achieved in the
      system, and to discuss about providing some alternative ideas to the implemented
      policies. The existing universal coverage previous to the crisis, as acknowledged
      by the law, has changed last year and the new figure of 'insured person' has been
      introduced into the system. These persons are now the only ones eligible to
      receive healthcare under the public coverage. New co-payments have been
      introduced for drugs, and retired persons must also pay a 10% co-payment (which
      was 0% before) at the chemist office. Healthcare institutions have also
      implemented several policies to manage tough budget constraints. Some regions
      have privatized healthcare management of some hospitals (as Madrid) to control
      budget and presumably to obtain a higher efficiency. Different initiatives
      dealing with human resources and external purchases are also presented in this
      paper to mostly achieve budget control. The majority of the changes have been
      pure budget cuts and a reorganization of the system and institutions is still
      needed. 

PMID- 23977972
TI  - US FDA patient-reported outcome guidance: great expectations and unintended
      consequences.
AB  - Release of the US FDA patient-reported outcome (PRO) guidance raised expectations
      within the pharmaceutical industry for the use of PRO measures in support of
      labeling claims. The FDA developed the guidance with admirable intent, and the
      recommendations within this document are based on sound scientific principles.
      However, implementation of the guidance has been somewhat inconsistent within the
      Study Endpoints and Label Development (SEALD) and across the various FDA
      reviewing divisions. Industry and regulatory bodies need to work toward gaining
      common ground to best support registration of treatments that could extend
      patients' lives, reduce symptoms, and/or improve health-related quality of life.
      PROs are valuable tools in communicating these messages, and realistic
      implementation of the FDA PRO Guidance may truly facilitate this process. 

PMID- 23977973
TI  - Health technology assessment and comparative effectiveness research: a
      pharmaceutical industry perspective.
AB  - We briefly review the characteristics of several established health technology
      assessment (HTA) programs in industrialized societies including Germany, the UK
      and France. Special attention is paid on two issues: the position of HTA in
      coverage decision making and the role of economic assessment in evaluation
      processes. Although law makers in the USA have barred the use of NICE's
      cost/quality-adjusted life year or similar health economics approaches by public
      payers for coverage decision making, there are suggestions of prioritizing
      relative efficacy evaluation over economic assessment under a comparative
      effectiveness research (CER) framework to inform payment rates of public payers
      (an approach similar to German and French HTA processes). However, such an
      approach is unlikely to prove viable. It should also be noted that, if cost
      considerations are made explicit in US CER policy decisions, CER may become an
      unsustainable approach undermined by a conflicting emphasis on both cost
      containment and a demand for costly comparative evidence. On the other hand,
      properly designed CER initiatives can serve as a facilitator of more efficient
      research activities and drug development models. With these points in mind, the
      likely pathway of US CER is explored and the plausible impact on industry
      innovation is discussed. 

PMID- 23977974
TI  - A review of cost-effectiveness evaluations as part of national health technology
      assessments of biologic DMARDs in the treatment of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune chronic disease which is associated
      with an increasing disability in patients and high socioeconomic burden. Given
      the large number of economic evaluations considered by national health technology
      assessments (HTAs), this review attempts to clarify whether results from biologic
      disease-modifying antirheumatic drugs (DMARDs) economic evaluations form the
      basis of official recommendation by national HTA agencies in Australia, Canada,
      Scotland and England. The results show that evidence of cost-effectiveness was
      not equally perceived by decision makers and did not have equal weightage in
      defining the official listing of biologic DMARDs for the treatment of RA. As it
      has been demonstrated in previous studies, major barriers exist for the
      integration of cost-effectiveness and cost-utility results with national HTA
      activity. In fact, as shown in this review, even when such analysis are
      available, cost-minimization and comparative effectiveness studies seemed to be
      preferred by some HTA agencies as tools to inform allocation of healthcare
      resources. 

PMID- 23977975
TI  - Reforms and initiatives in Scotland in recent years to encourage the prescribing
      of generic drugs, their influence and implications for other countries.
AB  - Scotland has introduced a number of initiatives to enhance the prescribing of low
      cost generic drugs versus originators and patent products in a class where these
      are seen as similar. The objective of this review is to appraise the influence of
      the various measures on subsequent utilization patterns and expenditure in high
      volume classes to provide guidance. This review is principally a narrative review
      of published studies. The authors' found supply-side measures resulted in generic
      prices as low as 3% of pre-patent loss prices. Multiple demand-side measures
      resulted in high international non-proprietary name prescribing, and a
      considerable increase in prescribing efficiency for the proton pump inhibitors,
      statins, renin-angiotensin inhibitor drugs and selective serotonin reuptake
      inhibitors. There were no specific activities encouraging the prescription of
      losartan versus other angiotensin receptor blockers or risperidone versus other
      atypical antipsychotic drugs following generics and no change in their
      utilization patterns post generics. The authors can conclude multiple measures
      are needed to change physician prescribing habits. Authorities cannot rely on any
      'spillover' effects to affect future prescribing, even in closely related
      classes. 

PMID- 23977976
TI  - Harmonization of reimbursement and regulatory approval processes: a systematic
      review of international experiences.
AB  - A considerable degree of overlap exists between reimbursement and regulatory
      approval of health technologies, and harmonization of certain aspects is both
      possible and feasible. Various models to harmonization have been suggested in
      which a number of practical attempts have been drawn from. Based on a review of
      the literature, approaches can be categorized into those focused on reducing
      uncertainty and developing economies of scale in the evidentiary requirements;
      and/or aligning timeframes and logistical aspects of the review process. These
      strategies can further be classified based on the expected level of structural
      and organizational change required to implement them into the existing processes.
      Passive processes require less modification, whereas active processes are
      associated with greater restructuring. Attempts so far at harmonization have
      raised numerous legal and practical issues and these must be considered when
      introducing a more harmonized framework into the existing regulatory and
      reimbursement arrangements. 

PMID- 23977977
TI  - Does framing of cancer survival affect perceived value of care? A willingness-to
      pay survey of US residents.
AB  - AIMS: To investigate the relationship between the framing of survival gains and
      the perceived value of cancer care. METHODS: Through a population-based survey of
      2040 US adults, respondents were randomized to one of the two sets of
      hypothetical scenarios, each of which described the survival benefit for a new
      treatment as either an increase in median survival time (median survival), or an
      increase in the probability of survival for a given length of time (landmark
      survival). Each respondent was presented with two randomly selected scenarios
      with different prognosis and survival improvements, and asked about their
      willingness to pay (WTP) for the new treatments. RESULTS: Predicted WTP increased
      with survival benefits and respondents' income, regardless of how survival
      benefits were described. Framing therapeutic benefits as improvements in landmark
      rather than median time survival increased the proportion of the population
      willing to pay for that gain by 11-35%, and the mean WTP amount by 42-72% in the
      scenarios we compared. CONCLUSION: How survival benefits are described may
      influence the value people place on cancer care.

PMID- 23977978
TI  - Reviewing and piloting methods for decreasing discount rates; someone, somewhere
      in time.
AB  - There has been substantial debate on the need for decreasing discounting for
      monetary and health gains in economic evaluations. Next to the discussion on
      differential discounting, a way to identify the need for such discounting
      strategies is through eliciting the time preferences for monetary and health
      outcomes. In this article, the authors investigate the perceived time preference
      for money and health gains through a pilot survey on Dutch university students
      using methods on functional forms previously suggested. Formal objectives of the
      study were to review such existing methods and to pilot them on a convenience
      sample using a questionnaire designed for this specific purpose. Indeed, a
      negative relation between the time of delay and the variance of the discounting
      rate for all models was observed. This study was intended as a pilot for a large
      scale population-based investigation using the findings from this pilot on
      wording of the questionnaire, interpretation, scope and analytic framework. 

PMID- 23977979
TI  - The effect of severity of depressive disorder on economic burden in a university
      hospital in Singapore.
AB  - BACKGROUND: Depressive disorder is treatable but costly, thus influencing quality
      of life of people. AIM: Determine direct and indirect costs incurred by
      depressive disorder in Singapore. METHODS: A 1-year prospective naturalistic
      study was conducted in a university mood disorder center between 2007 and 2008.
      Patients with primary International Classification of Disease-10 diagnosis of
      depressive disorder were recruited. Disease costs between mild, moderate and
      severe depression, and cost predictors were analyzed and determined. RESULTS:
      Forty nine patients completed the study. Mean annual total costs per patient were
      US$7638. Indirect costs (81%) dominated the total costs. Approximately 50% of
      indirect costs were associated with loss of productivity and unemployment. Higher
      education level, higher mean Hamilton Rating Scale for Depression score and
      number of suicide attempts were independent variables associated with increased
      direct costs while mean Hamilton Rating Scale for Depression scale score was an
      independent variable for indirect costs. CONCLUSION: Medical cost saving
      strategies should focus on indirect costs.

PMID- 23977980
TI  - HBV reactivation in an occult HBV infection patient treated with prednisone for
      nephrotic syndrome: case report and literature review.
AB  - BACKGROUND: Reactivation of hepatitis B virus (HBV), characterized by increased
      levels of serum HBV DNA, abnormal liver function and hepatic failure, is a
      frequent complication of immunosuppressive therapy and chemotherapy in patients
      with HBV infection. However, reactivation of occult HBV infection with
      immunosuppressive therapy or chemotherapy is rare. CASE PRESENTATION: A 77-year
      old man was diagnosed with nephrotic syndrome and IgM nephropathy with unclear
      pathogenesis. Liver function was normal, HBV-related serum markers were negative
      and HBV DNA titer was below the upper limits of normal. Two months following the
      start of prednisone therapy for his nephrotic syndrome, laboratory tests revealed
      a substantial increase in serum transaminase levels (ALT: 490 IU/L; AST: 149
      IU/L) and an elevation of HBV DNA level (3.42*10(6) copies/ml). We tested stored
      kidney tissue for HBsAg and HBcAg using immunohistochemistry and found the sample
      to be HBcAg positive, allowing us to confirm the etiology of nephropathy as an
      occult HBV infection. The cause of the hepatitis was thought to be HBV
      reactivation, so we immediately administered lamivudine. One month after the
      initiation of daily lamivudine treatment, laboratory tests revealed that serum
      levels of transaminases had improved (ALT: 35 IU/L; AST: 17 IU/L). Patient
      examination one year later showed that HBeAg had decreased with a concomitant
      increase of HBeAb, the quantity of HBV DNA was undetectable, and liver function
      and renal function had stabilized. CONCLUSION: This is the first report
      describing HBV reactivation in an occult HBV infection patient treated with oral
      prednisone for nephrotic syndrome. HBV-associated antigen should be regularly
      tested for in patients with unknown etiological glomerulonephritis in areas with
      high HBV viral popular and even in those with no clinical evidence for diagnosis
      of HBV.

PMID- 23977981
TI  - Automated analysis of immunoglobulin genes from high-throughput sequencing: life
      without a template.
AB  - BACKGROUND: Immunoglobulin (that is, antibody) and T cell receptor genes are
      created through somatic gene rearrangement from gene segment libraries.
      Immunoglobulin genes are further diversified by somatic hypermutation and
      selection during the immune response. Studying the repertoires of these genes
      yields valuable insights into immune system function in infections, aging,
      autoimmune diseases and cancers. The introduction of high throughput sequencing
      has generated unprecedented amounts of repertoire and mutation data from
      immunoglobulin genes. However, common analysis programs are not appropriate for
      pre-processing and analyzing these data due to the lack of a template or
      reference for the whole gene. RESULTS: We present here the automated analysis
      pipeline we created for this purpose, which integrates various software packages
      of our own development and others', and demonstrate its performance. CONCLUSIONS:
      Our analysis pipeline presented here is highly modular, and makes it possible to
      analyze the data resulting from high-throughput sequencing of immunoglobulin
      genes, in spite of the lack of a template gene. An executable version of the
      Automation program (and its source code) is freely available for downloading from
      our website: http://immsilico2.lnx.biu.ac.il/Software.html.

PMID- 23977982
TI  - Controllable growth of conducting polymers shell for constructing high-quality
      organic/inorganic core/shell nanostructures and their optical-electrochemical
      properties.
AB  - High-quality metal oxide/conducting polymer (CP) heterostructured nanoarrays are
      fabricated by controllable electrochemical polymerization of CP shells on
      preformed metal oxides nanostructures for both electrochromic and electrochemical
      energy storage applications. Coaxial and branched CP shells can be obtained on
      different backbones (nanowire, nanorod, and nanoflake) simply by controlling the
      electrodeposition time. "Solvophobic" and "electrostatic" interactions are
      proposed to account for the preferential growth of CP along metal oxides to form
      core/shell heterostructures. The coaxial TiO2/polyaniline core/shell nanorod
      arrays exhibit remarkable electrochromic performance with rich color changes,
      fast optical modulation, and superior cycling stability. In addition, the
      Co3O4/polyaniline core/shell nanowire arrays are evaluated as an anode material
      of Li ion battery and exhibit enhanced electrochemical property with higher and
      more stable capacity than the bare Co3O4 nanowires electrode. These unique
      organic-inorganic heterostructures with synergy pave the way for developing new
      functional materials with enhanced properties or new applications. 

PMID- 23977984
TI  - Size effect and odd-even alternation in the melting of single and stacked AgSCn
      layers: synthesis and nanocalorimetry measurements.
AB  - We report a systematic study of melting of layered lamella of silver
      alkanethiolates (AgSCn). A new synthesis method allows us to independently change
      the thickness of the crystal in two ways-by modulating chain length (n = 7-18)
      and by stacking these crystals to a specific layer number (m = 1-10). This method
      produces magic size lamella, having a well-spaced discrete melting point, Tm,
      distribution. Nanocalorimetry shows stepwise increases in Tm, as the lamella
      thickness increases by integer increments of chain length. The relationship
      between Tm and the inverse thickness follows the linear scaling law of Gibbs
      Thomson effect. Layer stacking dramatically changes the degree and nature of size
      effect melting. There is odd/even effect in stacked 2, 3, and 4 layers. Tm values
      of single-layer and multilayer samples do not show noticeable odd/even
      alternation. We develop a phenomenological model of size effect based on the
      cumulative excess free energy, G(excess), contributions of four spatially
      separate regions of the crystal: surface, Ag-S central plane, substrate
      interface, and interlayer interface. The selective appearance of the odd/even
      effect is due to the significant stabilization (1.4 kJ/mol) of interlamellae
      interfaces of odd-chain samples, possibly due to registration/packing.
      Stabilization occurs only for the mobile lamellae situated close to the free
      surface, and thus 2-layer samples show the highest degree of stabilization. X-ray
      diffraction shows that the chains are tilted 18 degrees  with respect to the
      basal plane normal but that the van der Waals gap is 0.3 A smaller for crystals
      with odd chains.

PMID- 23977983
TI  - Modulators of the microRNA biogenesis pathway via arrayed lentiviral enabled RNAi
      screening for drug and biomarker discovery.
AB  - MicroRNAs (miRNAs) are small endogenous and conserved non-coding RNA molecules
      that regulate gene expression. Although the first miRNA was discovered well over
      sixteen years ago, little is known about their biogenesis and it is only recently
      that we have begun to understand their scope and diversity. For this purpose, we
      performed an RNAi screen aimed at identifying genes involved in their biogenesis
      pathway with a potential use as biomarkers. Using a previously developed miRNA 21
      (miR-21) EGFP-based biosensor cell based assay monitoring green fluorescence
      enhancements, we performed an arrayed short hairpin RNA (shRNA) screen against a
      lentiviral particle ready TRC1 library covering 16,039 genes in 384-well plate
      format, and interrogating the genome one gene at a time building a panoramic view
      of endogenous miRNA activity. Using the BDA method for RNAi data analysis, we
      nominate 497 gene candidates the knockdown of which increased the EGFP
      fluorescence and yielding an initial hit rate of 3.09%; of which only 22, with
      reported validated clones, are deemed high-confidence gene candidates. An
      unexpected and surprising result was that only DROSHA was identified as a hit out
      of the seven core essential miRNA biogenesis genes; suggesting that perhaps
      intracellular shRNA processing into the correct duplex may be cell dependent and
      with differential outcome. Biological classification revealed several major
      control junctions among them genes involved in transport and vesicular
      trafficking. In summary, we report on 22 high confidence gene candidate
      regulators of miRNA biogenesis with potential use in drug and biomarker
      discovery. 

PMID- 23977985
TI  - Interplay between autophagy and programmed cell death in mammalian neural stem
      cells.
AB  - Mammalian neural stem cells (NSCs) are of particular interest because of their
      role in brain development and function. Recent findings suggest the intimate
      involvement of programmed cell death (PCD) in the turnover of NSCs. However, the
      underlying mechanisms of PCD are largely unknown. Although apoptosis is the best
      defined form of PCD, accumulating evidence has revealed a wide spectrum of PCD
      encompassing apoptosis, autophagic cell death (ACD) and necrosis. This mini
      review aims to illustrate a unique regulation of PCD in NSCs. The results of our
      recent studies on autophagic death of adult hippocampal neural stem (HCN) cells
      are also discussed. HCN cell death following insulin withdrawal clearly provides
      a reliable model that can be used to analyze the molecular mechanisms of ACD in
      the larger context of PCD. More research efforts are needed to increase our
      understanding of the molecular basis of NSC turnover under degenerating
      conditions, such as aging, stress and neurological diseases. Efforts aimed at
      protecting and harnessing endogenous NSCs will offer novel opportunities for the
      development of new therapeutic strategies for neuropathologies.

PMID- 23977986
TI  - The uniqueness of the plant mitochondrial potassium channel.
AB  - The ATP-inhibited Plant Mitochondrial K(+) Channel (PmitoKATP) was discovered
      about fifteen years ago in Durum Wheat Mitochondria (DWM). PmitoKATP catalyses
      the electrophoretic K(+) uniport through the inner mitochondrial membrane;
      moreover, the co-operation between PmitoKATP and K(+)/H(+) antiporter allows such
      a great operation of a K(+) cycle to collapse mitochondrial membrane potential
      (DeltaPsi) and DeltapH, thus impairing protonmotive force (Deltap). A possible
      physiological role of such DeltaPsi control is the restriction of harmful
      reactive oxygen species (ROS) production under environmental/oxidative stress
      conditions. Interestingly, DWM lacking Deltap were found to be nevertheless fully
      coupled and able to regularly accomplish ATP synthesis; this unexpected behaviour
      makes necessary to recast in some way the classical chemiosmotic model. In the
      whole, PmitoKATP may oppose to large scale ROS production by lowering DeltaPsi
      under environmental/oxidative stress, but, when stress is moderate, this occurs
      without impairing ATP synthesis in a crucial moment for cell and mitochondrial
      bioenergetics.

PMID- 23977987
TI  - Floridoside suppresses pro-inflammatory responses by blocking MAPK signaling in
      activated microglia.
AB  - Inflammatory conditions mediated by activated microglia lead to chronic neuro
      degenerative diseases such as Alzheimer's, Parkinson's, and Huntington's
      diseases. This study was conducted to determine the effect of floridoside
      isolated from marine red algae Laurencia undulata on LPS (100 ng/ml) activated
      inflammatory responses in BV-2 microglia cells. The results show that floridoside
      has the ability to suppress pro-inflammatory responses in microglia by markedly
      inhibiting the production of nitric oxide (NO) and reactive oxygen species (ROS).
      Moreover, floridoside down-regulated the protein and gene expression levels of
      iNOS and COX-2 by significantly blocking the phosphorylation of p38 and ERK in BV
      2 cells. Collectively, these results indicate that floridoside has the potential
      to be developed as an active agent for the treatment of neuro-inflammation.

PMID- 23977988
TI  - Human extracellular superoxide dismutase (EC-SOD) expression in transgenic
      chicken.
AB  - Extracellular superoxide dismutase (EC-SOD) is a metalloprotein and functions as
      an antioxidant enzyme. In this study, we used lentiviral vectors to generate
      transgenic chickens that express the human EC-SOD gene. The recombinant
      lentiviruses were injected into the subgerminal cavity of freshly laid eggs.
      Subsequently, the embryos were incubated to hatch using phases II and III of the
      surrogate shell ex vivo culture system. Of 158 injected embryos, 16 chicks (G0)
      hatched and were screened for the hEC-SOD by PCR. Only 1 chick was identified as
      a transgenic bird containing the transgene in its germline. This founder (G0)
      bird was mated with wild-type hens to produce transgenic progeny, and 2
      transgenic chicks (G1) were produced. In the generated transgenic hens (G2), the
      hEC-SOD protein was expressed in the egg white and showed antioxidant activity.
      These results highlight the potential of the chicken for production of
      biologically active proteins in egg white.

PMID- 23977989
TI  - Curcumin ameliorates TNF-alpha-induced ICAM-1 expression and subsequent THP-1
      adhesiveness via the induction of heme oxygenase-1 in the HaCaT cells.
AB  - Adhesion molecules such as ICAM-1 are important in the infiltration of leukocytes
      into the site of inflammation. In this study, we investigated the inhibitory
      effects of curcumin on ICAM-1 expression and monocyte adhesiveness as well as its
      underlying action mechanism in the TNF-alpha-stimulated keratinocytes. Curcumin
      induced expression of heme oxygenase-1 (HO-1) in the human keratinocyte cell line
      HaCaT. In addition, curcumin induced Nrf2 activation in dose- and time-dependent
      manners in the HaCaT cells. Curcumin suppressed TNF-alpha- induced ICAM-1
      expression and subsequent monocyte adhesion, which were reversed by the addition
      of tin protoporphyrin IX (SnPP), a specific inhibitor of HO-1, or HO-1 knockdown
      using siRNA. Furthermore, Nrf2 knockdown using siRNA reversed the inhibitory
      effect of curcumin on the TNF-alpha-induced ICAM-1 expression and adhesion of
      monocytes to keratinocytes. These results suggest that curcumin may exert its
      anti-inflammatory activity by suppressing the TNF-alpha-induced ICAM-1 expression
      and subsequent monocyte adhesion via expression of HO-1 in the keratinocytes.

PMID- 23977990
TI  - EvoSNP-DB: A database of genetic diversity in East Asian populations.
AB  - Genome-wide association studies (GWAS) have become popular as an approach for the
      identification of large numbers of phenotype-associated variants. However,
      differences in genetic architecture and environmental factors mean that the
      effect of variants can vary across populations. Understanding population genetic
      diversity is valuable for the investigation of possible population specific and
      independent effects of variants. EvoSNP-DB aims to provide information regarding
      genetic diversity among East Asian populations, including Chinese, Japanese, and
      Korean. Non-redundant SNPs (1.6 million) were genotyped in 54 Korean trios (162
      samples) and were compared with 4 million SNPs from HapMap phase II populations.
      EvoSNP-DB provides two user interfaces for data query and visualization, and
      integrates scores of genetic diversity (Fst and VarLD) at the level of SNPs,
      genes, and chromosome regions. EvoSNP-DB is a web-based application that allows
      users to navigate and visualize measurements of population genetic differences in
      an interactive manner, and is available online at
      [http://biomi.cdc.go.kr/EvoSNP/].

PMID- 23977991
TI  - Activation of JNKs is essential for BMP9-induced osteogenic differentiation of
      mesenchymal stem cells.
AB  - Although BMP9 is highly capable of promoting osteogenic differentiation of
      mesenchymal stem cell (MSCs), the molecular mechanism involved remains to be
      fully elucidated. Here, we explore the possible involvement and detail role of
      JNKs (c-Jun N-terminal kinases) in BMP9-induced osteogenic differentiation of
      MSCs. It was found that BMP9 stimulated the activation of JNKs in MSCs. BMP9
      induced osteogenic differentiation of MSCs was dramatically inhibited by JNKs
      inhibitor SP600125. Moreover, BMP9-activated Smads signaling was decreased by
      SP600125 treatment in MSCs. The effects of inhibitor are reproduced with
      adenoviruses expressing siRNA targeted JNKs. Taken together, our results revealed
      that JNKs was activated in BMP9-induced osteogenic differentiation of MSCs. What
      is most noteworthy, however, is that inhibition of JNKs activity resulted in
      reduction of BMP9-induced osteogenic differentiation of MSCs, implying that
      activation of JNKs is essential for BMP9 osteoinductive activity.

PMID- 23977992
TI  - Sorption and photodegradation processes govern distribution and fate of
      sulfamethazine in freshwater-sediment microcosms.
AB  - The antibiotic sulfamethazine can be transported from manured fields to surface
      water bodies. We investigated the degradation and fate of sulfamethazine in pond
      water using (14)C-phenyl-sulfamethazine in small pond water microcosms containing
      intact sediment and pond water. We found a 2.7-day half-life in pond water and
      4.2-day half-life when sulfamethazine was added to the water (5 mg L(-1) initial
      concentration) with swine manure diluted to simulate runoff. Sulfamethazine
      dissipated exponentially from the water column, with the majority of loss
      occurring via movement into the sediment phase. Extractable sulfamethazine in
      sediment accounted for 1.9-6.1% of the applied antibiotic within 14 days and then
      declined thereafter. Sulfamethazine was transformed mainly into nonextractable
      sediment-bound residue (40-60% of applied radioactivity) and smaller amounts of
      photoproducts. Biodegradation, as indicated by metabolite formation and (14)CO2
      evolution, was less significant than photodegradation. Two photoproducts
      accounted for 15-30% of radioactivity in the water column at the end of the 63
      day study; the photoproducts were the major degradates in the aqueous and
      sediment phases. Other unidentified metabolites individually accounted for <7% of
      radioactivity in the water or sediment. Less than 3% of applied radioactivity was
      mineralized to (14)CO2. Manure input significantly increased sorption and binding
      of sulfamethazine residues to the sediment. These results show concurrent
      processes of photodegradation and sorption to sediment control aqueous
      concentrations and establish that sediment is a sink for sulfamethazine and
      sulfamethazine-related residues. Accumulation of the photoproducts and
      sulfamethazine in sediment may have important implications for benthic organisms.

PMID- 23977993
TI  - The synthesis of benzo[f]isoindole-1,3-dicarboxylates via an i2-induced 1,3
      dipolar cycloaddition reaction.
AB  - An I2-induced 1,3-dipolar cycloaddition reaction has been developed for the
      synthesis of benzo[f]isoindole-1,3-dicarboxylates from quinones and N-substituted
      amino esters. The reaction proceeds in good to excellent yields in one step from
      3 equiv of amino ester to react with the quinone structure. The utility of this
      transformation has been highlighted by its use for the construction of
      benzo[f]isoindole-1,3-dicarboxylates, which have been identified in natural
      products exhibiting important biological activities. 

PMID- 23977995
TI  - In vitro pharmacological and toxicological effects of norterpene peroxides
      isolated from the Red Sea sponge Diacarnus erythraeanus on normal and cancer
      cells.
AB  - Eight cyclic peroxide norterpenoids, compounds 1-8, have been isolated and
      characterized from the Red Sea sponge Diacarnus erythraeanus, including two new
      norsesterterpene derivatives (3, 4). Among these metabolites, (-)-muqubilin A (5)
      (nine cell lines analyzed) and the new compounds 3 and 4 (seven cell lines
      analyzed) displayed mean IC50 growth inhibitory concentrations in vitro of <10
      MUM, while the remaining compounds (1, 6-8) were inactive in these cancer cell
      lines. Compound 5 displayed no selectivity between normal and cancer cells in
      terms of in vitro growth inhibition. Quantitative video microscopy analysis
      carried out on (-)-muqubilin A-treated cells validated the data obtained by means
      of the MTT colorimetric assay, while flow cytometry analysis revealed ROS
      production but no induction of apoptosis in cancer cells.

PMID- 23977996
TI  - Influence of the interfacial phase on the structural integrity and oxygen
      permeability of a dual-phase membrane.
AB  - Compositing fluorite Ce0.8Gd0.2O2-delta (CGO) oxide with perovskite
      La0.4Ba0.6Fe0.8Zn0.2O3-delta (LBFZ) oxide leads to the formation of a minor
      interfacial BaCeO3 phase upon sintering at 1400  degrees C. This interfacial
      composition assures a gastight ceramic membrane with fine grain-boundary
      structure, in which the LBFZ phase exhibits an improved oxygen permeability over
      the pristine LBFZ membrane on the same volumetric basis. The presence of the
      BaCeO3 phase effectively preserves the structural integrity of the composition by
      limiting the interfacial diffusion of barium ions between LBFZ and CGO. In
      comparison, replacing CGO with Y0.08Zr0.92O2-delta in the system results in a
      substantially low oxygen flux due to an overwhelming interfacial diffusion and,
      consequently, a heavy degradation of LBFZ. Besides structural reinforcement, the
      high interface between LBFZ and CGO benefits oxygen transport, as is proven
      through variation of the oxygen partial pressure on the feed side of the membrane
      and operation temperature. Furthermore, the trade-off between LBFZ loading and
      interfacial diffusion yields an optimal CGO loading at 40 wt %, which exhibits an
      oxygen flux of 0.84 cm(3)/cm(2).min at 950  degrees C. In summary, the minor
      interfacial binding between CGO and LBFZ grains is constructive in easing oxygen
      crossover in the phase boundary with the exception of maintaining membrane
      structural stability under oxygen permeation conditions. 

PMID- 23977997
TI  - Role of venous stenting in the management of inoperable intracranial
      arteriovenous malformations.

PMID- 23977998
TI  - An introduction to 'Science and medicine in football'.

PMID- 23977999
TI  - Innovative in vitro method to predict rate and extent of drug delivery to the
      brain across the blood-brain barrier.
AB  - The relevant parameters for predicting rate and extent of access across the blood
      brain barrier (BBB) are fu,plasma (unbound fraction in plasma), Vu,brain
      (distribution volume in brain) and Kp,uu,brain (ratio of free concentrations in
      plasma and brain). Their estimation still requires animal studies and in vitro
      low throughput experiments which make difficult the screening of new CNS
      candidates. The aim of the present work was to develop a new whole in vitro high
      throughput method to predict drug rate and extent of access across the BBB. The
      system permits estimation of fu,plasma, Vu,brain and Kp,uu,brain in a single
      experimental system, using in vitro cell monolayers in different conditions. From
      the ratios of the apparent permeability values (Papp) with the adequate
      mathematical analysis the relevant parameters can be estimated. Papp of ten model
      compounds has been obtained in MDCKII and MDCK-Mdr1cell monolayers in the absence
      and presence of albumin and brain homogenate. The ratio of Papp in the absence
      and presence of albumin allows estimation of in vitro fu,plasma. Papp in the
      presence of brain homogenate is used to estimate fu,brain and Vu,brain.
      Kp,uu,brain is estimated from the apical to basal versus basal to apical
      clearances. The BBB parameters obtained with the new method were predictive of
      the in vivo behavior of candidates. In vitro fu,plasma, Kp,uu,brain and Vu,brain
      (calculated with Papp from MDCKII cell line) presented a good correlation with in
      vivo fu,plasma, Kp,uu,CSF and Vu,brain published values (r=0.92; r=0.85; and
      r=0.99 respectively). Despite its simplicity the predictive performance is fairly
      good considering the reduced number of tested compounds with different
      physicochemical and transport properties. Further experimental modifications
      could be checked to optimize the method, but the present data support its
      feasibility. As other in vitro cell culture models, the system is suitable for
      miniaturization and robotization to allow high throughput screening of CNS
      candidates.

PMID- 23978000
TI  - Distribution of sulfathiazole in honey, beeswax, and honeybees and the
      persistence of residues in treated hives.
AB  - This study was performed to evaluate the distribution and depletion of
      sulfathiazole in different beehive matrices: honey, honeybees, "pre-existing"
      honeycomb, "new" honeycomb, and capping wax. Sulfathiazole was dissolved in sugar
      syrup or directly powdered on the combs, the matrices were sampled at different
      time points, and sulfathiazole residues were quantified by high-performance
      liquid chromatography with fluorescence detection. In honey, the higher
      concentration of sulfathiazole (180 mg kg(-1)) occurred 2 weeks after the last
      treatment in syrup. In beeswax, drug concentration was higher than in honey,
      particularly with powder administration, with a maximum level (340 mg kg(-1)) 3
      days following the last treatment. The strongest contamination in honeybees (28
      mg kg(-1)) was achieved with sulfathiazole administered in powder 3 days after
      the second treatment. The high persistence of sulfathiazole in the different
      beehive matrices suggests that it could be a reliable marker of previous
      treatments performed by beekeepers. 

PMID- 23978001
TI  - Vibrating-charge-driven water pump controlled by the deformation of the carbon
      nanotube.
AB  - The directed transport of water molecules in a single-walled carbon nanotube
      (SWNT) based on a ratchet effect is investigated by molecular dynamics
      simulations. The system is driven far away from thermal equilibrium by an
      additional deterministic perturbation of a vibrating charge, and the spatial
      inversion symmetry is broken by the continuous deformations of the SWNT. It is
      well-known that the water flux across a circular channel decreases when the
      channel is narrowed or deformed. However, our simulation results show that the
      water flux almost increases linearly within a deformation of 1.9 A. There exists
      an optimized value of deformation at which the pumping capacity takes its maximum
      value. Moreover, the direction of transport even exhibits a change of sign with
      narrowing the carbon nanotube. 

PMID- 23978002
TI  - Effect of malaria transmission reduction by insecticide-treated bed nets (ITNs)
      on the genetic diversity of Plasmodium falciparum merozoite surface protein (MSP
      1) and circumsporozoite (CSP) in western Kenya.
AB  - BACKGROUND: Although several studies have investigated the impact of reduced
      malaria transmission due to insecticide-treated bed nets (ITNs) on the patterns
      of morbidity and mortality, there is limited information on their effect on
      parasite diversity. METHODS: Sequencing was used to investigate the effect of
      ITNs on polymorphisms in two genes encoding leading Plasmodium falciparum vaccine
      candidate antigens, the 19 kilodalton blood stage merozoite surface protein-1
      (MSP-1(19kDa)) and the Th2R and Th3R T-cell epitopes of the pre-erythrocytic
      stage circumsporozoite protein (CSP) in a large community-based ITN trial site in
      western Kenya. The number and frequency of haplotypes as well as nucleotide and
      haplotype diversity were compared among parasites obtained from children <5 years
      old prior to the introduction of ITNs (1996) and after 5 years of high coverage
      ITN use (2001). RESULTS: A total of 12 MSP-1(19kDa) haplotypes were detected in
      1996 and 2001. The Q-KSNG-L and E-KSNG-L haplotypes corresponding to the FVO and
      FUP strains of P. falciparum were the most prevalent (range 32-37%), with an
      overall haplotype diversity of > 0.7. No MSP-1(19kDa) 3D7 sequence-types were
      detected in 1996 and the frequency was less than 4% in 2001. The CSP Th2R and
      Th3R domains were highly polymorphic with a total of 26 and 14 haplotypes,
      respectively detected in 1996 and 34 and 13 haplotypes in 2001, with an overall
      haplotype diversity of > 0.9 and 0.75 respectively. The frequency of the most
      predominant Th2R and Th3R haplotypes was 14 and 36%, respectively. The frequency
      of Th2R and Th3R haplotypes corresponding to the 3D7 parasite strain was less
      than 4% at both time points. There was no significant difference in nucleotide
      and haplotype diversity in parasite isolates collected at both time points.
      CONCLUSION: High diversity in these two genes has been maintained overtime
      despite marked reductions in malaria transmission due to ITNs use. The frequency
      of 3D7 sequence-types was very low in this area. These findings provide
      information that could be useful in the design of future malaria vaccines for
      deployment in endemic areas with high ITN coverage and in interpretation of
      efficacy data for malaria vaccines based on 3D7 parasite strains.

PMID- 23978004
TI  - A bio-inspired, small molecule electron-coupled-proton buffer for decoupling the
      half-reactions of electrolytic water splitting.
AB  - Electron-coupled-proton buffers (ECPBs) allow H2 and O2 evolution to be separated
      from each other in time during the electrolysis of water. Natural photosynthetic
      systems achieve an analogous feat during water splitting and employ a range of
      intermediate redox mediators such as quinone derivatives to aid this process.
      Drawing on this natural example, we show that a low molecular weight quinone
      derivative is capable of decoupling H2 evolution from O2 evolution at scale
      during electrochemical water splitting. This work could significantly lower the
      cost of ECPBs, paving the way for their more widespread adoption in water
      splitting. 

PMID- 23978005
TI  - Lymphatic transport of puerarin occurs after oral administration of different
      lipid-based formulations to unconscious lymph duct-cannulated rats.
AB  - This study investigated the potential of targeted intestinal lymphatic transport
      of puerarin via a lipid formulation approach. Three formulations of PEG
      nanoemulsion, nanosuspension and an oil suspension containing puerarin were
      examined with the lymph-cannulated anaesthetized rat model. Plasma and lymph
      samples were analyzed by HPLC. Lymph triglyceride was measured using an enzymatic
      colorimetric technique. After 8 h, the total administered dose accumulated in the
      thoracic lymph duct was analyze. Nanoemulsion, nanosuspension and oil suspension
      was 0.065 +/- 0.006%, 0.137 +/- 0.018%, 0.021 +/- 0.002% of the administered
      dose, respectively. In nanoemulsion, nanosuspension and oil suspension group, the
      systemic bioavailability of oral puerarin was 11%, 16% and 11% for lymph
      cannulated rats, 41%, 67% and 18% for control rats. Absorption into the
      intestinal lymph should thus contribute to ~30%, 51% and 7% of the systemic
      bioavailable puerarin. This data indicated that lipid-based nano drug formulation
      produced higher lymph concentrations of puerarin than oil suspension. The
      nanosuspension formulation may be considerable in terms of increased local
      concentrations in lymphoid tissue.

PMID- 23978006
TI  - Suppression of ionic liquid gate-induced metallization of SrTiO3(001) by oxygen.
AB  - Ionic liquid gating of three terminal field effect transistor devices with
      channels formed from SrTiO3(001) single crystals induces a metallic state in the
      channel. We show that the metallization is strongly affected by the presence of
      oxygen gas introduced external to the device whereas argon and nitrogen have no
      effect. The suppression of the gating effect is consistent with electric field
      induced migration of oxygen that we model by oxygen-induced carrier annihilation.

PMID- 23978007
TI  - Aging and the control of binocular fixations during reading.
AB  - Older adults (65 + years) often have greater difficulty in reading than young
      adults (18-30 years). However, the extent to which this difficulty is
      attributable to impaired eye-movement control is uncertain. To address this
      issue, the alignment and location of the two eyes' fixations during reading were
      monitored for young and older adults. Older adults showed typical patterns of
      reading difficulty but the results revealed no age differences in the alignment
      or location of the two eyes' fixations. Thus, the difficulty older adults
      experience in reading is not related to oculomotor control, which appears to be
      preserved into older age.

PMID- 23978003
TI  - Mitochondria in lung diseases.
AB  - Mitochondria are autonomous cellular organelles that oversee a variety of
      functions such as metabolism, energy production, calcium buffering and cell fate
      determination. Regulation of their morphology and diverse activities beyond
      energy production are being recognized as playing major roles in cellular health
      and dysfunction. This review is aimed at summarizing what is known regarding
      mitochondrial contributions to pathogenesis of lung diseases. Emphasis is given
      to understanding the importance of structural and functional aspects of
      mitochondria in both normal cellular function (based on knowledge from other cell
      types) and in development and modulation of lung diseases such as asthma, chronic
      obstructive pulmonary disease, cystic fibrosis and cancer. Emerging techniques
      that allow examination of mitochondria, and potential strategies to target
      mitochondria in the treatment of lung diseases are also discussed. 

PMID- 23978008
TI  - Age-related decline of precision and binding in visual working memory.
AB  - Working memory declines with normal aging, but the nature of this impairment is
      debated. Studies based on detecting changes to arrays of visual objects have
      identified two possible components to age-related decline: a reduction in the
      number of items that can be stored, or a deficit in maintaining the associations
      (bindings) between individual object features. However, some investigations have
      reported intact binding with aging, and specific deficits arising only in
      Alzheimer's disease. Here, using a recently developed continuous measure of
      recall fidelity, we tested the precision with which adults of different ages
      could reproduce from memory the orientation and color of a probed array item. The
      results reveal a further component of cognitive decline: an age-related decrease
      in the resolution with which visual information can be maintained in working
      memory. This increase in recall variability with age was strongest under
      conditions of greater memory load. Moreover, analysis of the distribution of
      errors revealed that older participants were more likely to incorrectly report
      one of the unprobed items in memory, consistent with an age-related increase in
      misbinding. These results indicate a systematic decline with age in working
      memory resources that can be recruited to store visual information. The paradigm
      presented here provides a sensitive index of both memory resolution and feature
      binding, with the potential for assessing their modulation by interventions. The
      findings have implications for understanding the mechanisms underpinning working
      memory deficits in both health and disease.

PMID- 23978010
TI  - The effects of aging on haptic 2D shape recognition.
AB  - We use the image-mediation model (Klatzky & Lederman, 1987) as a framework to
      investigate potential sources of adult age differences in the haptic recognition
      of two-dimensional (2D) shapes. This model states that the low-resolution,
      temporally sequential, haptic input is translated into a visual image, which is
      then reperceived through the visual processors, before it is matched against a
      long-term memory representation and named. In three experiments we tested groups
      of 12 older (mean age 73.11) and three groups of 12 young adults (mean age 22.80)
      each. In Experiment 1 we confirm age-related differences in haptic 2D shape
      recognition, and we show the typical age * complexity interaction. In Experiment
      2 we show that if we facilitate the visual translation process, age differences
      become smaller, but only with simple shapes and not with the more complex
      everyday objects. In Experiment 3 we target the last step in the model (matching
      and naming) for complex stimuli. We found that age differences in exploration
      time were considerably reduced when this component process was facilitated by
      providing a category name. We conclude that the image-mediation model can explain
      adult-age differences in haptic recognition, particularly if the role of working
      memory in forming the transient visual image is considered. Our findings suggest
      that sensorimotor skills thought to rely on peripheral processes for the most
      part are critically constrained by age-related changes in central processing
      capacity in later adulthood.

PMID- 23978011
TI  - Does aging affect recall more than recognition memory?
AB  - Although it is generally agreed that recall performance declines more than
      recognition memory performance in the course of normal aging, there are some
      dissenting voices. There are also a few empirical findings that cast doubt on
      that conclusion. In light of these ambiguities the present experiments were
      designed to answer the question in a more definitive fashion. Over a series of 3
      experiments, groups of younger and older adults performed recall and recognition
      tests successively on the same lists of words. Several analyses of the resulting
      data converge on the conclusion that there is a consistent age-related decrement
      in recall that is disproportionately greater than the age-related decrement in
      recognition. This conclusion is in line with several theoretical accounts of age
      related differences in cognitive processing and also with emerging evidence from
      cognitive neuroscience.

PMID- 23978009
TI  - Multisensory integration, aging, and the sound-induced flash illusion.
AB  - The present study examined age-related differences in multisensory integration
      and the role of attention in age-related differences in multisensory integration.
      The sound-induced flash illusion--the misperception of the number of visual
      flashes due to the simultaneous presentation of a different number of auditory
      beeps--was used to examine the strength of multisensory integration in older and
      younger observers. The effects of integration were examined when discriminating 1
      3 flashes, 1-3 beeps, or 1-3 flashes presented with 1-3 beeps. Stimulus
      conditions were blocked according to these conditions with baseline (unisensory)
      performance assessed during the multisensory block. Older participants
      demonstrated greater multisensory integration--a greater influence of the beeps
      when judging the number of visual flashes--than younger observers. In a second
      experiment, the role of attention was assessed using a go/no-go paradigm. The
      results of Experiment 2 replicated those of Experiment 1. In addition, the
      strength of the illusion was modulated by the sensory domain of the go/no-go
      task, though this did not differ by age group. In the visual go/no-go task we
      found a decrease in the illusion, yet in the auditory go/no-go task we found an
      increase in the illusion. These results demonstrate that older individuals
      exhibit increased multisensory integration compared with younger individuals.
      Attention was also found to modulate the strength of the sound-induced flash
      illusion. However, the results also suggest that attention was not likely to be a
      factor in the age-related differences in multisensory integration.

PMID- 23978012
TI  - [Relapse of acute leukemia after allogeneic stem cell transplantation: its
      mechanisms and strategies for the prevention and treatment].

PMID- 23978013
TI  - [Prevalence of EBV infection in patients with allogeneic hematopoietic stem cell
      transplantation].
AB  - OBJECTIVE: To analyze the prevalence of Epstein Barr Virus (EBV) in patients
      following allogeneic hematopoietic stem cell transplantation (allo-HSCT).
      METHODS: We retrospectively analyzed the clinical characteristics of 720 patients
      received allo-HSCT from January 2010 through December 2011 in the Stem Cell
      Transplant Center of People's Hospital. RESULTS: Of 720 patients (469 male
      presented and 251 females), with a median age of 30 years (range, 2 to 67 years)
      old, 66 patients were presented with EBV reactivation. The cumulative incidence
      of EBV reactivation was (9.3+/-1.1)%, with a median days of 54.5 (range, 18 to
      253 days). During one- year post-transplantation, the cumulative incidences of
      EBV reactivation in sibling allo-HSCT, haploidentical HSCT and unrelated donor
      HSCT were (1.3+/-0.7)%, (13.7+/-1.7)%, and (9.1+/-4.4)%, respectively. In
      patients with haplo-identical HSCT, the cumulative incidences of EBV viremia,
      probable EBV disease, and post-transplant lymphoproliferative disease (PTLD) were
      (5.8+/-1.1)%, (5.7+/-1.1)%, and (2.3+/-0.7)%. The mortality was (33.9+/-5.9)% in
      all patients with EBV infection: (63.6+/-15.8)% in PTLD, (42.3+/-9.9)% in
      probable EBV disease, (13.8+/-6.5)% in EBV viremia. By univariate and
      multivariate analysis, the use of ATG was an independent risk factor for EBV
      infection. CONCLUSION: EBV reactivation is a common complication in patients with
      allo- HSCT, especially high mortality in PTLD and probable EBV disease. The use
      of ATG was an independent risk factor for EBV infection.

PMID- 23978014
TI  - [Prognostic significance of EBMT score system for hematological malignancies with
      allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To evaluate the impact of EBMT score system in patients with
      hematological malignancies received allogeneic hematopoietic stem cell
      transplantation (allo-HSCT). METHODS: A total of 144 consecutive patients were
      analyzed retrospectively. According to the EBMT score system, including age,
      disease status before transplantation, interval between diagnoses to
      transplantation, donor/recipient sex match and donor type, patients were divided
      into 3 risk groups: low risk (score 0-1), intermediate risk (score 2-3) and high
      risk (score 4-7). RESULTS: The median follow-up duration were 413 (10-1827) days
      for all patients and 837 (166-1827) days for alive patients. The estimated 4-year
      overall survival (OS), transplant-related mortality (TRM) and relapse rate (RR)
      were (57.5+/-4.6)%, (21.6+/-3.7)% and (42.7+/-6.1)%, respectively. The 4-year OS,
      TRM and RR were (72.2+/-9.0)%, (8.1+/-4.5)% and (27.3+/-8.7)% in the low-risk
      group, significantly superior to both intermediate-risk group [(57.7+/-6.0)%,
      (23.1+/-5.1)% and (44.9+/-8.3)%] and high-risk group [(36.9+/-10.2)%, (33.5+/
      9.2)% and (51.5+/-11.8)%] (P<0.01, 0.02 and 0.009 for OS, TRM and RR
      respectively). CONCLUSION: The EBMT score system provides prognostic significance
      for OS, TRM and RR in patients with hematological malignancies received allo
      HSCT.

PMID- 23978015
TI  - [Prognostic implications of hematopoietic cell transplantation-specific
      comorbidity index on non-relapse mortality and overall survival after allogeneic
      hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To study the prognostic implications of hematopoietic cell
      transplantation-specific comorbidity index (HCT-CI) on non-relapse mortality
      (NRM) and overall survival (OS) in patients underwent allogeneic hematopoietic
      stem cell transplantation (allo-HSCT). METHODS: Clinical data of 161 cases
      received allo-HSCT from July 2003 to November 2010 were analyzed retrospectively.
      The prognostic significance of HCT-CI, age, sex, conditioning regimens, disease
      status before transplantation, graft source and the degree of HLA matches for NRM
      and OS was conducted by COX regression model. The prognostic impact of HCT-CI on
      NRM and OS was performed in all patients under different disease status before
      transplantation. RESULTS: Of the 161 cases with allo-HSCT, 3-year NRM and OS were
      26.4% and 61.4% respectively. NRM at 3 years in patients with HCT-CI score 0, 1-2
      and >=3 were 14.9%, 24.5% and 52.7% respectively. And OS at 3 years were 68.9%,
      64.6% and 34.7% respectively. There were significant differences between HCT-CI
      score 0 and >=3 groups for NRM and OS (P<0.01). High-risk disease status before
      transplantation (NRM: RR=3.35, P<0.01;OS: RR=3.53, P<0.01) and HCT-CI score>=3
      (NRM: RR=6.85, P<0.01;OS: RR=3.77, P<0.01)were independent risk factors by COX
      regression model. In the subgroup analysis according to disease status, high
      score of HCT-CI was associated with poor OS (P<0.01) and high NRM (P<0.01) in
      patients with low-risk, but not in those with high-risk disease status.
      CONCLUSION: HCT-CI score and disease status before transplantation are
      independent risk factors for patients received allo-HSCT. HCT-CI score have
      prognostic implication for NRM and OS in patients with low-risk disease status,
      but not in high-risk group.

PMID- 23978016
TI  - [The kinetics and prognosis of platelet reconstitution after unmanipulated
      haploidentical stem cell transplantation without in vitro T cell depletion].
AB  - OBJECTIVE: To explore the kinetics of platelet reconstitution and its prognostic
      significance in patients received unmanipulated haploidentical stem cell
      transplantation (Haplo-HSCT) without in vitro T cell depletion. METHODS: A total
      of 291 patients received Haplo-HSCT without in vitro T cell depletion between
      January 2007 to December 2008 were retrospectively reviewed. They were
      categorized into 3 groups according to the platelet count on day 30, day 60 and
      day 90: (1) persistent thrombocytopenia (Group A) was defined as the platelet
      count never reached 50*109/L on the three time points; (2) unstable
      thrombocytopenia (Group B): the platelet count recovered to a level of 50*109/L
      by day 30 or 60 or 90, yet did not reach a level of more than 100*109/L; (3) non
      thrombocytopenia (Group C): the platelet count was higher than 100*109/L on day
      90. The kinetics of platelet reconstitution, overall survival (OS) and treatment
      related mortality (TRM) were compared between 3 groups. RESULTS: Of the 291
      consecutive patients, 288 cases engrafted successfully and 262 cases were
      platelet transfusion independent. The median intervals of neutrophil and platelet
      engraftment were 13 (9-29) days and 17 (7-180) days, respectively. The cumulative
      incidence of grade III-IV acute graft versus host disease (GVHD) on day 100 and
      chronic GVHD at 3 years were 14.7% and 56.4% respectively. OS and TRM at 3 years
      were 64.6% and 22.3% respectively. At the end of the follow-up, 266 cases were
      platelet transfusion independent: including 71 (24.4%) cases in Group A, 147
      (50.5%) in Group B and 73 (25.1%) in Group C. OS in group A, B and C was 38.0%,
      69.4% and 80.8% (P<0.05) respectively. TRM in Group A, B and C was 53.5%, 17.7%
      and 1.4% (P<0.05) respectively. Persistent thrombocytopenia was related with
      lower OS and higher TRM in multivariate analysis. CONCLUSION: Persistent
      thrombocytopenia was common after Haplo-HSCT without in vitro T cell depletion,
      and patients with persistent thrombocytopenia have poor OS and higher TRM.

PMID- 23978017
TI  - [Bilateral lung transplantation for bronchiolitis obliterans after allogeneic
      bone marrow transplantation: a case report and literature review].
AB  - OBJECTIVE: To explore the feasibility and efficiency of lung transplantation in
      the treatment of bronchiolitis obliterans (BO) after allogeneic bone marrow
      transplantation (allo-BMT). METHODS: We reported one case of bilateral lung
      transplantation for BO after allo-BMT and reviewed the related literatures.
      RESULTS: A 23 year-old man diagnosed as BO after allo-BMT underwent a sequential
      bilateral lung transplantation through bilateral anterolateral thoracotomy
      without sternal division. The patient suffered from acute rejection on post
      operation day (POD) 2, and cured by mechanical ventilation, large dose of
      methylprednisolone and gamma globulin. The patient was transferred out of the
      intensive care unit on POD 14 and discharged from the hospital on POD 43. Chest
      CT scans and pulmonary function tests showed good performance in 3 and 6 months
      follow-up period. CONCLUSION: BO is one of the late common non-infectious
      pulmonary complication after allo-BMT. For patients who have no response to
      medication, lung transplantation is the only efficient treatment choice so far,
      which can prolong survival and improve the quality of life. However, limited by
      small samples, optimal surgery time and appropriate care of postoperative
      complications still need accumulation of experience by multicenter and large
      samples studies.

PMID- 23978018
TI  - [Effects of p38MAPK inhibitor on the occurrence of acute GVHD and intestine
      damage after allogeneic hematopoietic stem cell transplantation in mice].
AB  - OBJECTIVE: To explore the effects of p38MAPK inhibitor SB203580 (SB) on the
      occurrence of acute GVHD and intestine damage after allogeneic hematopoietic stem
      cell transplantation (allo-HSCT) in mice. METHODS: Sixty BALB/c mice, as
      recipients, were randomized to control group, irradiation group, model group and
      intervention group. C57BL/6 mice, as donors, were raised to prepare the bone
      marrow cells (BMCs) and spleen cells (SCs), which were injected into irradiated
      recipients mice by tail vein. Except control group, other groups accepted 7.5Gy
      total body irradiation. Model group and intervention group were infused with BMCs
      5*106 and SCs 5*105 by less than 4 h after irradiation. SB was injected into
      intervention group by intraperitoneally, but only DMSO for model group. The
      general status and survival rate of each group were evaluated. The expression of
      p-p38MAPK, Fas and FasL in intestine were determined by RT-PCR, Western blot and
      immunohistochemistry (IHC). RESULTS: The weight changes of intervention group
      (13.00+/-0.50)% was significantly lighter than that of model group (25.00+/
      0.75)% (P<0.05). The clinical score of acute GVHD in the intervention group
      (3.33+/-0.82) was significantly lower than that of model group (6.33+/-1.36)
      (P<0.05). The expression levels of p-p38MAPK, Fas and FasL in small intestine of
      intervention group (1.43+/-0.02, 0.81+/-0.03, 0.97+/-0.03) were lower than those
      of model group (1.76+/-0.05, 1.52+/-0.04, 1.48+/-0.04). CONCLUSION: SB inhibited
      the activation of p38MAPK and Fas/ FasL signal pathway and alleviated the
      apoptosis of small intestine. And SB could relieve small intestine damages
      induced by allogeneic T lymphocytes.

PMID- 23978019
TI  - [Association of the ratio of regulatory and effector T cells with recurrence and
      chronic graft-versus-host disease after allogeneic hematopoietic stem cell
      transplantation].
AB  - OBJECTIVE: To investigate the association of the ratio of regulatory and effector
      T cells with recurrence and chronic graft-versus-host disease (cGVHD) after
      allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Thirty
      patients with hematological malignancies who underwent allo-HSCT were classified
      as recurrence with cGVHD (n=4), non-recurrence with cGVHD (n=14), recurrence
      without cGVHD (n=5) and non-recurrence without cGVHD (n=7). The different
      percentage of CD4+CD25-CD69+ regulatory T cells in bone marrow and
      CD4+CD25+FoxP3+ regulatory T cells, Th1 cells and Th17 cells in peripheral blood
      were analyzed by flow cytometry. RESULTS: There were no significant differences
      in all these T-cell subsets among different groups (P>0.05). While the ratio of
      CD4+CD25-CD69+ regulatory T cells and Th1 cells (0.211+/-0.177) in 9 recurrence
      patients was significant higher than that (0.133+/-0.160) in 21 non-recurrence
      patients (P=0.033). The ratio were also significance between recurrence without
      cGVHD and non-recurrence without cGVHD patients (0.167+/-0.073 vs 0.073+/-0.057,
      P=0.048), and between recurrence with cGVHD and non-recurrence without cGVHD
      patients (0.218+/-0.113 vs 0.073+/-0.057, P=0.024). Furthermore, the ratio of
      CD4+CD25+FoxP3+ regulatory T cells and Th17 cells was significant lower (1.975+/
      2.045) in 18 cGVHD patients than that of 12 without cGVHD patients (3.198+/
      1.132, P=0.010), and the ratio was also significant lower in non-recurrence
      patients with cGVHD (1.695+/-1.178) than that of without cGVHD (3.446+/-1.376,
      P=0.028). CONCLUSION: Our results show that the ratio of CD4+CD25-CD69+
      regulatory T cells and Th1 cells raise in recurrence patients, and the ratio of
      CD4+CD25+FoxP3+ regulatory T cells and Th17 decrease in cGVHD patients, which
      suggest that the ratio of regulatory and effector T cells had association with
      recurrence and cGVHD in patients with allo-HSCT.

PMID- 23978020
TI  - [Meta-analysis of imatinib mesylate with or without interferon for chronic-phase
      chronic myeloid leukemia].
AB  - OBJECTIVE: Meta-analysis of the efficiencies of imatinib mesylate (IM) with or
      without interferon for chronic myeloid leukemia-chronic phase (CML-CP) patients.
      METHODS: Published studies of IM with or without interferon for CML-CP patients
      as first-line therapy were collected from PubMed, Cochrane Central Register of
      Controlled Trials (CENTRAL) of the Cochrane Library, China National Knowledge
      Infrastructure (CNKI), China Biology Medicine (CBM), VIP information and WANFANG
      database. References of retrieved articles were also identified. The quality of
      each randomized controlled trial (RCT) was evaluated by the Cochrane
      collaboration's tool for assessing the risk of bias. Data analysis was performed
      with RevMan 5.1. RESULTS: A total of 5 articles involving 1754 patients were
      included. Meta-analysis results showed that there were no statistical differences
      between IM with interferon and IM monotherapy for the complete cytogenetic
      response (CCyR) rate at 12 months,but IM with interferon could improve major
      molecular response (MMR) rate at 12 months (OR=1.57, 95% CI: 1.26-1.96, P=0.02).
      Furthermore, IM combined with pegylated-interferon demonstrated superiority for
      MMR at 12 months (OR=2.43, 95% CI: 1.78-3.33, P<0.01). CONCLUSION: Combination of
      IM and interferon does not increase CCyR rate, but improve MMR rate at 12 months.

PMID- 23978021
TI  - [The binding mechanisms of F VIII Trp1707Ser mutation-associated inhibitor].
AB  - OBJECTIVE: To investigate the binding mechanisms of FVIII Trp1707Ser mutation
      associated inhibitor. METHODS: The APPT, PT, TT, Fg and FVIII:C were detected to
      make phenotypic diagnosis of haemophilia A. Inhibitors titer were measured by
      Bethesda method. Long distance-PCR (LD-PCR) and sequence-specific PCR were
      adopted for screening the intron 22 and intron 1 inversions respectively. FVIII
      coding and boundary sequences were analyzed by direct DNA sequencing. Inhibitor
      was reacted with different segments of FVIII, including heavy chain and its
      components A1 and A2, light chain and its components A3, C1 and C2. Corrected
      test was used to measure the remaining F VIII:C (% ) by adding pooled normal
      plasmas. After labeling purified inhibitors with biotin, western blot was
      performed to further confirm the binding reactions between inhibitors and
      segments. RESULTS: The haemophilia A patient had mild deficiency of FVIII:C
      (1.1%) and had high FVIII inhibitor titer of 18.4 BU. A mutation c.97223C>G in
      exon 14 of F8 gene resulted to p.Trp1707Ser was identified by DNA sequencing.
      Corrected test showed that the remaining F VIII:C was increased when inhibitors
      reacted with heavy chain and light chain, especially with heavy chain. The
      remaining FVIII:C was also increased in the A2 and C2 domain reactions. No
      significant differences were seen in the A1, A3 and C1 domain reactions. Antigen
      antibody reaction bands were confirmed by western blots when degenerated B-domain
      deleted recombinant FVIII, A2 and C2 were used as antigens. CONCLUSION: The
      binding sites of FVIIITrp1707Ser mutation inhibitor were the A2 domain of heavy
      chain and C2 domain of light chain. The binding reaction with heavy chain was
      more intense.

PMID- 23978022
TI  - [Clinical and molecular characteristics of hemoglobin New York in Guangxi
      populations].
AB  - OBJECTIVE: To analyze the clinical and molecular characteristics of hemoglobin
      New York in populations from Guangxi and provide reference data for screening
      thalassemia. METHODS: A total of 30 691 samples were screened by capillary
      electrophoresis, and then suspicious samples of Hb New York were identified by
      DNA sequencing and analysis of blood cell count. Gap-PCR and reverse dot blot
      hybridization method were used for the detection of common mutations of alpha and
      beta thalassemia in Chinese. RESULTS: The incidence of Hb New York was 0.12% in
      Guangxi. The hematological phenotype index (MCV, MCH, Hb New York, Hb A2) of 32
      Hb New York heterozygous cases were (91.00+/-5.19)fl, (29.42+/-2.04)pg, (44.10+/
      3.12)% and (2.80+/-0.29)% , respectively. The hematological phenotype index of 4
      Hb New York composited SEA heterozygous patients were (68.20+/-5.26) fl, (21.78+/
      2.15) pg, (36.60+/-2.00)% and (2.90+/-0.14)% , of 2 Hb New York composited WS
      heterozygous patients were (83.90+/-2.69) fl, (27.70+/-1.70) pg, (39.70+/-1.70)%
      and (3.50+/-0.21)%. There were statistical differences between three groups
      (P<0.05). HGB, MCV and MCH of Hb New York heterozygous and Hb New York composited
      WS heterozygous were normal, and patients with Hb New York composited SEA
      heterozygous showed mild anemia, decreased MCV and MCH. CONCLUSION: Most of Hb
      New York were heterozygous and no homozygotes in Guangxi. There were different
      hematological characteristics in different Hb New York heterozygous patients. Hb
      New York heterozygous had normal hematological phenotype, ant combined with other
      types of thalassemia could exhibit symptoms such as anemia.

PMID- 23978023
TI  - [Prognostic significance of the NPM-ALK fusion gene in bone marrow and peripheral
      blood for patients with anaplastic large cell lymphoma].
AB  - OBJECTIVE: To investigate the expression of NPM- ALK fusion gene in bone marrow
      (BM) and peripheral blood (PB) in anaplastic large cell lymphoma (ALCL) patients
      and its prognostic significance. METHODS: NPM- ALK fusion gene of 21 BM and 15 PB
      samples from patients with NPM-ALK positive ALCL was detected by RT- PCR, and the
      relationship between NPM- ALK expression and prognosis and clinical characters
      was evaluated. RESULTS: Of the 21 patients, 12 cases were male and 9 case were
      female with a median age of 9 (range, 2-14) years old. The median follow- up was
      31 months. Patients with a positive NPM-ALK expression in BM had a 3-years EFS of
      (35.6+/-18.6)%, compared with (91.7+/-8.0)% for patients with negative NPM-ALK
      (P=0.038). The incidence of positive expression in BM was significantly higher in
      patients who had more than 3 organs involved by tumor (P=0.032). 86.7% patients
      had a concordant results of NPM-ALK expression in PB and BM. CONCLUSION: We could
      evaluate the minimal disseminated disease of NPM-ALK positive ALCL patients by
      screening the NPM-ALK fusion gene in BM and PB by RT-PCR. The positive expression
      is associated with a poor prognosis and could be used for stratification of ALCL.

PMID- 23978024
TI  - [Congenital dyserythropoietic anemia type II with novel mutations in SEC23B and
      HFE2 genes: a Chinese family survey].
AB  - OBJECTIVE: To report novel mutations SEC23B gene in congenital dyserythropoietic
      anemia (CDA). METHODS: By direct sequencing method, we sequenced CDAN1 and SEC23B
      genes in a Chinese CDA II patient, presented with chronic fatigue and dark urine,
      as well as his family members. Serum hepcidin was assayed by mass spectrometry.
      RESULTS: We found a c.71G>A mutation and a c.74C> A mutation in the patient. In
      addition, a heterozygous c.55A>G mutation of HFE2 gene was found in some family
      members. The level of serum hepcidin of the patient was below the detection limit
      (<1 nmol/L). CONCLUSION: Contrary with what have been reported previously in the
      Europe, especially in the Italy, the gene mutations identified in this case was
      different and novel. The two novel mutations contribute to the diagnosis of CDAII
      and are the first report in East Asian CDAII patients.

PMID- 23978025
TI  - [Acute kidney injury induced by favism in children: a case report].

PMID- 23978026
TI  - [Predicting early response to immunosuppressive therapy in severe aplastic anemia
      by soluble transferrin receptor assay].
AB  - OBJECTIVE: To evaluate the value of serum soluble transferrin receptor (sTfR)
      concentration in predicting early response to immunosuppressive therapy (IST) in
      severe aplastic anemia (SAA). METHODS: Clinical data and hematologic responses of
      140 SAA patients treated with rabbit antithymocyte globulin (rATG) combination
      with cyclosporine in our hospital were retrospectively analyzed. Correlation of
      pre-IST baseline of sTfR and IST responses was statistically analyzed and
      receiver operating characteristic (ROC) curve was used to estimate the
      sensitivity and specificity of sTfR in prediction of early responses. RESULTS:
      Serum concentration of sTfR in very SAA (VSAA) patients were significantly lower
      than SAA and transfusion dependent non-SAA cases (P=0.001). The responders,
      especially at 3 months, had significantly higher pre- IST baseline of sTfR
      [median, 0.89 (range, 0.21-2.42) mg/L] than that [median, 0.58 (range, 0.13-1.88)
      mg/L] of non-responders (P=0.005). The cutoff level of 0.91 mg/L and 0.88 mg/L
      for predicting responses at 3 and 6 months were established based on the ROC
      curve, with the degree of accuracy of 65.0% and 60.7% respectively. Multivariate
      analysis showed that pre-IST baseline of sTfR was the independent factor of
      predicting response at 3 months (P=0.007) and at 6 months (P=0.021). CONCLUSION:
      As a indicator of bone marrow failure severity, sTfR could predict early response
      to IST therapy in aplastic anemia.

PMID- 23978027
TI  - [Identification of serum biomarkers for assessing minimal residual disease in
      acute leukemia by serum peptide pattern].
AB  - OBJECTIVE: To screen serum biomarkers for minimal residual disease (MRD)
      monitoring according to differential peptidomics profile in the serum from the
      patients with acute leukemia (AL) and healthy controls. METHODS: Serum
      polypeptides from 90 AL patients, 60 healthy controls and 20 patients with benign
      hematological disorders were enriched by copper chelate magnetic beads, and the
      peptidomics profile was obtained by matrix assisted laser desorption ionization
      time of flight mass spectrometry (MALDI-TOF-MS) analysis. And the intensities of
      differential peptides were calculated to assess MRD level. RESULTS: The
      diagnostic models by using support vector machine (SVM) algorithm according to
      differential peptides between AL patients and healthy controls with P<0.01 by t
      test were established. The sensitivity and specificity of distinguishing AL
      patients from healthy controls were 98% and 99%, respectively. The model obtained
      a sensitivity of 98% and a specificity of 96% for distinguishing newly-diagnosed
      AL patients from AL patients with hematological complete remission (AL-HCR). Then
      a sensitivity of 92% and a specificity of 93% were obtained for distinguishing
      patients with AL-CR from AL patients with molecular complete remission (AL- MR).
      The intensity of peptide with m/z (mass-to-charge ratio) 4468 was significantly
      higher in newly- diagnosed AL patients compared to healthy controls, and
      gradually decreased with the increase of remission degree, and it was not found
      increase in patients with benign hematological disorders. CONCLUSION: The SVM
      diagnostic model established by differential serum peptide profile could be used
      to discriminate AL patients with different stages of remission and to evaluate
      the treatment efficacy. The peptide of m/z 4468 could be used for MRD assessment,
      and continuous monitoring of its expression level will play an important role in
      the individual treatment and recurrence prediction.

PMID- 23978028
TI  - [Identification of glucose-6-phosphate dehydrogenase gene variants in Guangdong
      populations].

PMID- 23978029
TI  - [Prognostic significance of 18F-FDG PET/CT in aggressive non- Hodgkin's lymphoma:
      a 10-year retrospective study on 105 cases].

PMID- 23978030
TI  - [Can chronic myeloid leukemia be cured by tyrosine kinase inhibitor?].

PMID- 23978031
TI  - [Prevention of leukemia relapse after allogeneic hematopoietic stem cell
      transplantation].

PMID- 23978033
TI  - [Consensus of Chinese experts on cytogenetics and molecular genetic analysis for
      the diagnosis of hematologic disorders (2013)].

PMID- 23978032
TI  - [Secondary mediastinal diffuse large B cell lymphoma after the treatment of
      nodular sclerosis classical Hodgkin lymphoma: a case report].

PMID- 23978034
TI  - [Sorafenib monotherapy for FLT3-ITD positive acute myeloid leukemia: a case
      report].

PMID- 23978035
TI  - Impact of closing Canada's largest point-source of mercury emissions on local
      atmospheric mercury concentrations.
AB  - The Flin Flon, Manitoba copper smelter was Canada's largest point source of
      mercury emissions until its closure in 2010 after ~80 years of operation. The
      objective of this study was to understand the variables controlling the local
      ground-level air mercury concentrations before and after this major point source
      reduction. Total gaseous mercury (TGM) in air, mercury in precipitation, and
      other ancillary meteorological and air quality parameters were measured pre- and
      postsmelter closure, and mercury speciation measurements in air were collected
      postclosure. The results showed that TGM was significantly elevated during the
      time period when the smelter operated (4.1 +/- 3.7 ng m(-3)), decreased only 20%
      during the year following its closure, and remained ~2-fold above background
      levels. Similar trends were observed for mercury concentrations in precipitation.
      Several lines of evidence indicated that while smelter stack emissions would
      occasionally mix down to the surface resulting in large spikes in TGM
      concentrations (up to 61 ng m(-3)), the largest contributor to elevated TGM
      concentrations before and after smelter closure was from surface-air fluxes from
      mercury-enriched soils and/or tailings. These findings highlight the ability of
      legacy mercury, deposited to local landscapes over decades from industrial
      activities, to significantly affect local air concentrations via emissions/re
      emissions.

PMID- 23978036
TI  - Transgenic mouse strains as platforms for the successful discovery and
      development of human therapeutic monoclonal antibodies.
AB  - Transgenic mice have yielded seven of the ten currently-approved human antibody
      drugs, making them the most successful platform for the discovery of fully human
      antibody therapeutics. The use of the in vivo immune system helps drive this
      success by taking advantage of the natural selection process that produces
      antibodies with desirable characteristics. Appropriately genetically-engineered
      mice act as robust engines for the generation of diverse repertoires of affinity-
      matured fully human variable regions with intrinsic properties necessary for
      successful antibody drug development including high potency, specificity,
      manufacturability, solubility and low risk of immunogenicity. A broad range of
      mAb drug targets are addressable in these mice, comprising both secreted and
      transmembrane targets, including membrane multi-spanning targets, as well as
      human target antigens that share high sequence identity with their mouse
      orthologue. Transgenic mice can routinely yield antibodies with sub-nanomolar
      binding affinity for their antigen, with lead candidate mAbs frequently
      possessing affinities for binding to their target of less than 100 picomolar,
      without requiring any ex vivo affinity optimization. While the originator
      transgenic mice platforms are no longer broadly available, a new generation of
      transgenic platforms is in development for discovery of the next wave of human
      therapeutic antibodies. 

PMID- 23978037
TI  - Mammalian cell display and somatic hypermutation in vitro for human antibody
      discovery.
AB  - Human therapeutic antibody discovery has utilized a variety of systems, from in
      vivo immunization of human immunoglobulin-expressing mice, to in vitro display of
      antibody libraries. Of the in vitro antibody display technologies, mammalian cell
      display provides a number of advantages with the ability to co-select
      immunoglobulin molecules for high expression level in mammalian cells, native
      folding, and biophysical properties appropriate for drug development. Mammalian
      cell display has been achieved using either transient or stable expression
      systems, using a number of alternate transmembrane domains to present antibody on
      the cell surface. The unique capability of mammalian cells to present IgG in its
      fully post-translationally modified format also allows selection of antibodies
      for functional properties. One limitation of mammalian cell based systems,
      however, has been the smaller library size that can be presented compared to
      phage display approaches. Until recently, this has necessitated the use of
      libraries biased toward a particular antigen, such as libraries derived from
      immunized donors, to achieve success. An alternative approach has now been
      developed which recapitulates key aspects of the in vivo immune system through
      reproducing somatic hypermutation (SHM) in vitro. Libraries representing a naive
      human B lymphocyte antibody repertoire are created by PCR amplification of the
      rearranged (D)J segments of heavy and light chain variable regions from human
      donors and incorporating the resulting sequence diversity into panels of human
      germline VH and VL genes. The resulting antibodies are presented as full length
      IgG on the surface of HEK293 cells. After isolation of antibodies binding to
      individual target antigens, subsequent affinity maturation using in vitro SHM is
      induced by expression of activation-induced cytidine deaminase (AID). Selection
      of antibodies from naive fully human libraries using mammalian cell display
      coupled with in vitro SHM is an efficient methodology for the generation of high
      affinity human antibodies with excellent properties for drug development. 

PMID- 23978038
TI  - Antibody discovery from immune competent and immune transplanted mice.
AB  - Since Kohler and Milstein developed the process of generating hybridomas by
      fusing antibody secreting B cells with an immortal myeloma cell line, the
      techniques used to develop monoclonal antibodies for use as human therapeutics
      have progressed significantly. Here, we will briefly review hybridoma technology
      and the evolution of therapeutic antibodies for the treatment of human disease.
      We will focus on the evolution of humanized mouse models for the generation of
      therapeutic human antibodies, comparing the early models, such as severe combined
      immunodeficient (SCID) mice which do not engraft human leukocytes well due to
      residual innate immunity, to the more recently developed models such as non-obese
      diabetic (NOD)/SCID IL-2Rgamma-deficient mice in which numerous human
      hematopoietic lineages can be cultivated. Building on the identification of
      suitable host strains for the reconstitution of human immune cells, focus has now
      shifted onto humanizing the murine microenvironment in order to support human
      immune cell function. Although several recent studies have shown that the
      provision of human soluble factors can support maturation and function of human
      immune cells, particularly within the myeloid compartment, this does not appear
      to impact antibody production significantly. Moreover, models in which grafting
      of human tissues is performed to provide human microenvironments which support
      human leukocyte maturation do show improved humoral immune function, but require
      several surgical manipulations for generation of the model. Ultimately the most
      desirable scenario is to generate transgenic models that can be bred efficiently
      and express a sufficient number of human molecules to support functional human
      immune cells and several groups have made progress in making this idea a reality.
      These studies in the context of the generation of human antibodies will be
      discussed. 

PMID- 23978039
TI  - Nanoparticle-nanoparticle interactions in biological media by atomic force
      microscopy.
AB  - Particle-particle interactions in physiological media are important determinants
      for nanoparticle fate and transport. Herein, such interactions are assessed by a
      novel atomic force microscopy (AFM)-based platform. Industry-relevant CeO2,
      Fe2O3, and SiO2 nanoparticles of various diameters were made by the flame spray
      pyrolysis (FSP)-based Harvard Versatile Engineering Nanomaterials Generation
      System (Harvard VENGES). The nanoparticles were fully characterized structurally
      and morphologically, and their properties in water and biological media were also
      assessed. The nanoparticles were attached on AFM tips and deposited on Si
      substrates to measure particle-particle interactions. The corresponding force was
      measured in air, water, and biological media that are widely used in
      toxicological studies. The presented AFM-based approach can be used to assess the
      agglomeration potential of nanoparticles in physiological fluids. The
      agglomeration potential of CeO2 nanoparticles in water and RPMI 1640 (Roswell
      Park Memorial Institute formulation 1640) was inversely proportional to their
      primary particle (PP) diameter, but for Fe2O3 nanoparticles, that potential is
      independent of PP diameter in these media. Moreover, in RPMI+10% Fetal Bovine
      Serum (FBS), the corona thickness and dispersibility of the CeO2 are independent
      of PP diameter, while for Fe2O3, the corona thickness and dispersibility were
      inversely proportional to PP diameter. The present method can be combined with
      dynamic light scattering (DLS), proteomics, and computer simulations to
      understand the nanobio interactions, with emphasis on the agglomeration potential
      of nanoparticles and their transport in physiological media. 

PMID- 23978040
TI  - Iron halide-mediated regio- and stereoselective halosulfonylation of terminal
      alkynes with sulfonylhydrazides: synthesis of (E)-beta-chloro and bromo
      vinylsulfones.
AB  - Halosulfonylation of terminal alkynes was achieved with sulfonylhydrazides as the
      sulfonyl precursor and inexpensive iron halide as halide source in the presence
      of TBHP, allowing the regio- and stereoselective generation of (E)-beta-chloro
      and bromo vinylsulfones. 

PMID- 23978042
TI  - Bioactive proteins and energy value of okara as a byproduct in hydrothermal
      processing of soy milk.
AB  - The nutritional properties of raw okara obtained as a byproduct from six soybean
      varieties during hydrothermal cooking (HTC) of soy milk were assessed. The
      composition and residual activity (rTIA) of trypsin inhibitors (TIs), contents of
      lectin, proteins, fats, and carbohydrates, and energy values (EV) were correlated
      with the respective physicochemical properties of soybean and okara. Kunitz (KTI)
      and Bowman-Birk (BBI) TIs both comprised okara rTIA. TIs content was higher in
      okara (5.19-14.40%) than in soybean (3.10-12.17%), which additionally enriched
      okara by cysteine. Contents of KTI (r = 1.00;p < 0.05) and BBI (r = 0.89;p <
      0.05) as well as BBI monomeric (r = 0.89;p < 0.05) and polymeric forms (r =
      0.95;p < 0.05) in okara and in soybean were strongly correlated. Low urease index
      activity indicated that okara was heated adequately to inactivate antinutritional
      factors. The proximate composition of raw okara, advantageous rTIA, and a very
      low EV (2.74-3.78 kJ/g) qualify this byproduct for potential application in food
      preparation as a functional ingredient in dietary products. 

PMID- 23978043
TI  - Dielectric relaxation and solvation dynamics in a room-temperature ionic liquid:
      temperature dependence.
AB  - Dielectric relaxation, related polarization and conductivity, and solvation
      dynamics of the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate
      (BMI(+)PF6(-)) are studied via molecular dynamics computer simulations in the
      temperature range 300 K <= T <= 500 K. Two main bands of its dielectric loss
      spectrum show differing temperature behaviors. As T increases, the absorption
      band in the microwave region shifts to higher frequencies rapidly, whereas the
      location of the bimodal far-IR band remains nearly unchanged. Their respective
      intensities tend to decrease and increase. The static dielectric constant of
      BMI(+)PF6(-) is found to decrease weakly with T. The ultrafast inertial component
      of solvation dynamics remains largely unchanged, while their dissipative
      relaxation component becomes faster. Roles played by ion reorientations and
      translations in governing dynamic and static dielectric properties of the ionic
      liquid are examined. A brief comparison with available experimental results is
      also made. 

PMID- 23978044
TI  - Fast and persistent electrocatalytic water oxidation by Co-Fe Prussian blue
      coordination polymers.
AB  - The lack of an efficient, robust, and inexpensive water oxidation catalyst (WOC)
      is arguably the biggest challenge for the technological development of artificial
      photosynthesis devices. Here we report the catalytic activity found in a cobalt
      hexacyanoferrate (CoHCF) Prussian blue-type coordination polymer. This material
      is competitive with state-of-the-art metal oxides and exhibits an unparalleled
      long-term stability at neutral pH and ambient conditions, maintaining constant
      catalytic rates for weeks. In addition to its remarkable catalytic activity,
      CoHCF adds the typical properties of molecule-based materials: transparency to
      visible light, porosity, flexibility, processability, and low density. Such
      features make CoHCF a promising WOC candidate for advancement in solar fuels
      production. 

PMID- 23978045
TI  - Anti-erythropoietin antibody levels and its association with anaemia in different
      strains of semi-immune mice infected with Plasmodium berghei ANKA.
AB  - BACKGROUND: Malaria anaemia is still a major public health problem and its
      pathogenesis still unclear. Interestingly, the progression of anaemia is at
      relatively low parasitaemia with some mortality in the semi-immune individuals in
      the endemic areas despite adequate erythropoietin (EPO) synthesis. A recent study
      has shown that treatment with exogenous anti-erythropoietin (anti-EPO) antibodies
      (Ab) of infected mice gives protection against malaria infection, suggesting an
      important role for anti-EPO Ab in malaria. The objective of the study was to
      evaluate anti-EPO antibody levels in anaemic condition of different strains of
      semi-immune mice with malaria. METHODOLOGY: Semi-immune status was attained in
      four mice strains (Balb/c, B6, CBA and NZW) by repeated infections with
      104Plasmodium berghei ANKA, and treatment with chloroquine/pyrimethamine. ELISA
      was used to measure anti-EPO Ab, transferrin and EPO while inflammatory cytokines
      measurement was done using bead-based multiplex assay kit. RESULTS: The mean anti
      EPO Ab levels in the mice strains [Optical Density (OD) values at 450 nm: Balb/c
      (2.1); B6 (1.3); CBA (1.4) and NZW (1.7)] differed (p = 0.045), and were
      significantly higher when compared with uninfected controls, p < 0.0001, and mean
      anti-EPO Ab levels in the mice strains at recovery [OD values at 450 nm: Balb/c
      (1.8); B6 (1.1); CBA (1.5) and NZW (1.0) also differed (p = 0.0004).
      Interestingly, EPO levels were significantly high in NZW and low in Balb/c mice
      (p < 0.05), with those of B6 and CBA of intermediary values. Again, NZW were
      highly parasitaemic (20.7%) and the other strains (Balb/c, B6 and CBA) ranged
      between 2.2-2.8% (p = 0.015). Anti-EPO Ab correlated positively with extent of Hb
      loss (r = 0.5861; p = 0.003). Correlation of anti-EPO antibody with EPO was
      significant only in Balb/c mice (r = -0.83; p = 0.01). Significant levels of IL6
      and IFNgamma (p < 0.0001), both known to be associated with erythropoiesis
      suppression were observed in the Balb/c. Transferrin was significantly lower in
      Balb/c (p < 0.0001) when compared with the other mice strains (B6, CBA and NZW).
      CONCLUSION: This is the first ever report in estimating endogenous anti-EPO
      antibodies in malaria anaemia. The data presented here suggest that anti-EPO Ab
      is produced at infection and is associated with Hb loss. Host factors appear to
      influence anti-EPO antibody levels in the different strains of mice.

PMID- 23978046
TI  - Gold-nanoparticles-modified cellulose membrane coupled with laser
      desorption/ionization mass spectrometry for detection of iodide in urine.
AB  - We report an efficient method for the determination of iodide (I(-)) ions by
      using gold-iodide hybrid cluster ions on gold nanoparticles (Au NPs) modified
      mixed cellulose ester membrane (Au NPs-MCEM) by pulsed laser
      desorption/ionization mass spectrometry (LDI-MS). When I(-) ions were deposited
      and concentrated on the surfaces of Au NPs (32 nm) via strong Au(+)-I(-)
      interaction on the MECM, the Au NPs-MCEM was observed to function as an efficient
      surface-assisted LDI substrate with very low background noise. When pulsed laser
      radiation (355 nm) was applied, I(-) binding to Au NPs ions induced the
      enhancement of the desorption and ionization efficiency of gold-iodide hybrid
      cluster ions from the Au NPs surfaces. The reproducibility of the probe for both
      shot-to-shot and sample-to-sample (both less than 10%) ion production was also
      improved by the homogeneous nature of the substrate surface. Thus, it allows the
      accurate and precise quantification of I(-) ions in high-salinity real samples
      (i.e., edible salt samples and urine) at the nanomolar range. This novel LDI-MS
      approach provides a simple route for the high-speed analysis of I(-) ions with
      high sensitivity and selectivity in real biological samples. 

PMID- 23978047
TI  - Isolation, structures, and biological activities of triterpenoids from a Penares
      sp. marine sponge.
AB  - Six new triterpenoids (1-6) and the previously known penasterone,
      acetylpenasterol, and ergosta-4,24(28)-dien-3-one were isolated from a Penares
      sp. sponge collected from Vietnamese waters. Structures of the obtained compounds
      were established by extensive 1D and 2D NMR spectroscopy and mass spectrometry.
      Configurations of the triterpene epoxy lactones (1-4) were determined on the
      basis of NOESY and CD data and calculation of spin coupling constants and
      confirmed by X-ray crystallographic analysis of compound 2. The isolated
      triterpenoid 6 was cytotoxic against human leukemia HL-60 cells (IC50 = 9.7 MUM).

PMID- 23978049
TI  - Isothermal self-assembly of complex DNA structures under diverse and
      biocompatible conditions.
AB  - Nucleic acid nanotechnology has enabled researchers to construct a wide range of
      multidimensional structures in vitro. Until recently, most DNA-based structures
      were assembled by thermal annealing using high magnesium concentrations and
      nonphysiological environments. Here, we describe a DNA self-assembly system that
      can be tuned to form a complex target structure isothermally at any prescribed
      temperature or homogeneous condition within a wide range. We were able to achieve
      isothermal assembly between 15 and 69  degrees C in a predictable fashion by
      altering the strength of strand-strand interactions in several different ways,
      for example, domain length, GC content, and linker regions between domains. We
      also observed the assembly of certain structures under biocompatible conditions,
      that is, at physiological pH, temperature, and salinity in the presence of the
      molecular crowding agent polyethylene glycol (PEG) mimicking the cellular
      environment. This represents an important step toward the self-assembly of
      geometrically precise DNA or RNA structures in vivo. 

PMID- 23978050
TI  - Influence of the type of vegetable oil on the drug release profile from lipid
      core nanocapsules and in vivo genotoxicity study.
AB  - The use of rice bran (RB), soybean (SB) or sunflower seed (SF) oils to prepare
      lipid-core nanocapsules (LNCs) as controlled drug delivery systems was
      investigated. LNCs were prepared by interfacial deposition using the preformed
      polymer method. All formulations showed negative zeta potential and adequate
      nanotechnological characteristics (particle size 220-230  nm, polydispersity
      index < 0.20). The environmental safety was evaluated through an in vivo protocol
      (Allium cepa test) and LNCs containing RB, SB or SF oils did not present
      genotoxic potential. Clobetasol propionate (CP) was selected as a model drug to
      evaluate the influence of the type of vegetable oil on the control of the drug
      release from LNCs. Biphasic drug release profiles were observed for all
      formulations. After 168  h, the concentration of drug released from the
      formulation containing SF oil was lower (0.36  mg/mL) than from formulations
      containing SB (0.40  mg/mL) or RB oil (0.45  mg/mL). Good correlations between
      the consistency indices for the LNC cores and the burst and sustained drug
      release rate constants were obtained. Therefore, the type of the vegetal oil was
      shown as an important factor governing the control of drug release from LNCs.

PMID- 23978051
TI  - Quality of life of patients with ADPKD-Toranomon PKD QOL study: cross-sectional
      study.
AB  - BACKGROUND: The quality of life (QOL) of patients with autosomal dominant
      polycystic kidney disease (ADPKD) has not been investigated well. This study was
      performed to clarify the QOL of patients with ADPKD and to identify factors that
      affected their QOL. METHODS: The present cross-sectional study is part of a
      prospective observational study on the QOL of ADPKD patients. Patients with ADPKD
      who were referred to Toranomon Hospital between March 2010 and November 2012 were
      enrolled. The short form-36 (SF-36) questionnaire and our original 12-item
      questionnaire were used to evaluate QOL. We analyzed the results of the
      questionnaire survey and then investigated correlations between QOL and clinical
      features. RESULTS: A total of 219 patients (93 men and 126 women) were enrolled
      and their mean age was 55.1 +/- 10.8 years. There were 108 patients on dialysis.
      The SF-36 scores (PCS, MCS, and RCS) of all patients were significantly lower
      than the mean scores for the Japanese population. Stepwise multiple regression
      analysis demonstrated that Hb, serum Alb, ascites, and cerebrovascular disease
      all had a significant influence on the PCS, while mental disease had a
      significant influence on the MCS and serum Alb significantly influenced the RCS.
      The total liver and kidney volume (TLKV) and the dialysis status were not
      significantly associated with any of the SF-36 scores by multiple regression
      analysis, but TLKV was closely correlated with abdominal distention and
      distention had an important influence on QOL. Pain, sleep disturbance, heartburn,
      fever, gross hematuria, and anorexia also affected QOL, but these variables were
      not correlated with TLKV. CONCLUSIONS: Several factors influence QOL, so
      improving symptoms unrelated to TLKV as well as reducing abdominal distention can
      improve the QOL of ADPKD patients.

PMID- 23978052
TI  - Combination treatment in hypertension - the latest 2013 European Guidelines.

PMID- 23978053
TI  - Clostridium difficile antibodies: a patent evaluation (WO2013028810).
AB  - INTRODUCTION: Incidence and severity of Clostridium difficile infection (CDI) are
      increasing worldwide. Toxins A (TcdA) and B (TcdB) and host immune response are
      the major determinates of CD pathogenesis and represent a new, stimulating
      therapeutic target to control CDI. AREAS COVERED: The present patent and
      literature on the pathogenesis and treatment of CD were critically reviewed. The
      patent was described and put into clinical context, highlighting possible
      advantages and barriers to use. It consists of a blend of monoclonal antibodies
      (mAbs) and antigen-binding portions that neutralize TcdA, targeting the
      enterocyte-binding domain. It demonstrated good efficacy in in vivo models and
      seems promising in clinical practice. However, recent evidence reshaped the
      central role of TcdA. EXPERT OPINION: Current treatments are inadequate to
      control CDI and recurrence. Toxin-targeted mAbs are one of the most promising
      approaches for CDI, including infection by hypervirulent strains. At-risk
      subjects and those experiencing recurrence are the ideal targets for this second
      line treatment; however CDI epidemiology is fast-changing and mAbs may represent
      a powerful option also for other patients. The re-evaluation of the pathogenic
      role of TcdA may potentially limit the use of this product; however, the possible
      administration in combination with other therapeutic agents may optimize its
      efficacy.

PMID- 23978054
TI  - Sunlight-induced inactivation of human Wa and porcine OSU rotaviruses in the
      presence of exogenous photosensitizers.
AB  - Human rotavirus Wa and porcine rotavirus OSU solutions were irradiated with
      simulated solar UV and visible light in the presence of different
      photosensitizers dissolved in buffered solutions. For human rotavirus, the
      exogenous effects were greater than the endogenous effects under irradiation with
      full spectrum and UVA and visible light at 25  degrees C. For porcine rotavirus,
      the exogenous effects with UVA and visible light irradiation were only observed
      at high temperatures, >40  degrees C. The results from dark experiments conducted
      at different temperatures suggest that porcine rotavirus has higher
      thermostability than human rotavirus. Concentrations of 3'-MAP excited triplet
      states of 1.8 fM and above resulted in significant human rotavirus inactivation.
      The measured excited triplet state concentrations of <=0.45 fM produced by UVA
      and visible light irradiation of natural dissolved organic matter solutions were
      likely not directly responsible for rotavirus inactivation. Instead, the linear
      correlation for human rotavirus inactivation rate constant (kobs) with the phenol
      degradation rate constant (kexp) found in both 1 mM NaHCO3 and 1 mM phosphate
      buffered solutions suggested that OH radical was a major reactive species for the
      exogenous inactivation of rotaviruses. Linear correlations between rotavirus kobs
      and specific UV254 nm absorbance of two river-dissolved organic matter and two
      effluent organic matter isolates indicated that organic matter aromaticity may
      help predict formation of radicals responsible for rotavirus inactivation. The
      results from this study also suggested that the differences in rotavirus strains
      should be considered when predicting solar inactivation of rotavirus in sunlit
      surface waters. 

PMID- 23978056
TI  - (68)Ga/DOTA- and (64)Cu/NOTA-phthalocyanine conjugates as fluorescent/PET bimodal
      imaging probes.
AB  - In this paper, we describe the synthesis and characterization of a series of new
      bimodal probes combining water-soluble sulfonated zinc phthalocyanine (ZnPc) as a
      fluorescence imaging unit and either (68)Ga/1,4,7,10-tetraazocyclododecane
      N,N'N",N'"-tetraacetic acid (DOTA) or (64)Cu/1,4,7-triazacyclononane-1,4,7
      triacetic acid (NOTA) for PET imaging. The two moieties were linked through
      aliphatic chains of different lengths to modulate amphiphilicity. Labeling of
      DOTA- or NOTA-ZnPc conjugates with (68)Ga (t1/2 = 68 min) and (64)Cu (t1/2 = 12.7
      h) was performed at 100  degrees C for 15 min with >90% efficiency for all
      conjugates. In vitro plasma stability assays demonstrated high stability of the
      (64)Cu/NOTA-ZnPc conjugate, which remained intact over a 24 h time period, and
      reasonably high stability of the (68)Ga/DOTA-ZnPc conjugate, which released up to
      7% of free (68)Ga over a 3 h period. Based on in vitro plasma stability results,
      we performed biodistribution studies on two (64)Cu-labeled derivatives, which
      allowed us to select a single candidate for preliminary in vivo experiments.
      Fluorescence and PET imaging confirmed the potential of these novel conjugates to
      act as bimodal probes. 

PMID- 23978060
TI  - Beneficial effects of plant sources on the treatment of osteoporosis.
AB  - Osteoporosis causes bone loss, and makes bone to susceptible to fracture. The
      main cause of osteoporosis is estrogen deficiency. Estrogen, calcitonin, calcium,
      vitamin D and antioxidants can be used to prevent osteoporosis. For the treatment
      of osteoporosis, the potential biological activities of traditional medicines
      have been subjected to scientific evaluation, since synthetic drugs are
      considered to have several side effects and they lack efficacy. Therefore, more
      extensive research should be carried out to investigate the medicinal plants to
      be used as an alternative treatment for osteoporosis. The present review focuses
      on the scientific researches on the assessment of anti-osteoporotic activity of
      medicinal plants. 

PMID- 23978057
TI  - Mimicry of high-density lipoprotein: functional peptide-lipid nanoparticles based
      on multivalent peptide constructs.
AB  - We describe an approach for engineering peptide-lipid nanoparticles that function
      similarly to high-density lipoprotein (HDL). Branched, multivalent constructs,
      bearing multiple 23- or 16-amino-acid peptides, were designed, synthesized, and
      combined with phospholipids to produce nanometer-scale discoidal HDL-like
      particles. A variety of biophysical techniques were employed to characterize the
      constructs, including size exclusion chromatography, analytical ultracentrifuge
      sedimentation, circular dichroism, transmission electron microscopy, and
      fluorescence spectroscopy. The nanoparticles functioned in vitro (human and mouse
      plasma) and in vivo (mice) to rapidly remodel large native HDLs into small lipid
      poor HDL particles, which are key acceptors of cholesterol in reverse cholesterol
      transport. Fluorescent labeling studies showed that the constituents of the
      nanoparticles readily distributed into native HDLs, such that the peptide
      constructs coexisted with apolipoprotein A-I (apoA-I), the main structural
      protein in HDLs. Importantly, nanolipid particles containing multivalent peptides
      promoted efficient cellular cholesterol efflux and were functionally superior to
      those derived from monomeric apoA-I mimetic peptides. The multivalent peptide
      lipid nanoparticles were also remarkably stable toward enzymatic digestion in
      vitro and displayed long half-lives and desirable pharmacokinetic profiles in
      mice, providing a real practical advantage over previously studied linear or
      tandem helical peptides. Encouragingly, a two-week exploratory efficacy study in
      a widely used animal model for atherosclerosis research (LDLr-null mice) using
      nanoparticles constructed from a trimeric peptide demonstrated an exceptional 50%
      reduction in the plasma total cholesterol levels compared to the control group.
      Altogether, the studies reported here point to an attractive avenue for designing
      synthetic, HDL-like nanoparticles, with potential for treating atherosclerosis. 

PMID- 23978061
TI  - Characteristics of activated carbon and carbon nanotubes as adsorbents to remove
      annatto (norbixin) in cheese whey.
AB  - Removing annatto from cheese whey without bleaching has potential to improve whey
      protein quality. In this work, the potential of two activated carbon products and
      multiwalled carbon nanotubes (CNT) was studied for extracting annatto (norbixin)
      in aqueous solutions. Batch adsorption experiments were studied for the effects
      of solution pH, adsorbent mass, contact duration, and ionic strength. The
      equilibrium adsorption data were observed to fit both Langmuir and Freundlich
      isotherm models. The thermodynamic parameters estimated from adsorption isotherms
      demonstrated that the adsorption of norbixin on three adsorbents is exothermic,
      and the entropic contribution differs with adsorbent structure. The adsorption
      kinetics, with CNT showing a higher rate than activated carbon, followed the
      pseudo first order and second order rate expressions and demonstrated the
      significance of intraparticle diffusion. Electrostatic interactions were observed
      to be significant in the adsorption. The established adsorption parameters may be
      used in the dairy industry to decolorize cheese whey without applying bleaching
      agents. 

PMID- 23978062
TI  - Extending photoinduced charge separation lifetimes by using supramolecular
      design: guanine-perylenediimide G-quadruplex.
AB  - We report here a potassium-induced guanine quadruplex as a supramolecular
      platform for controlled assembly of electron donor-acceptor systems. A
      monodisperse, C4-symmetric octamer of a guanine-perylene-3,4,9,10
      bis(dicarboximide) conjugate (GPDI) was prepared in tetrahydrofuran. The two
      layers of cyclic guanine tetramers have the same direction of rotation, and the
      PDI moiety between the layers adopts a nearly eclipsed relationship (H
      aggregation), as revealed by small- and wide-angle X-ray scattering, NMR
      spectroscopy, and steady-state UV/vis absorption. Following photoexcitation of
      the PDI moiety in the quadruplex, charge separation occurs in tauCS = 98 +/- 12
      ps to give G(+*)-PDI(-*) that recombines in tauCR = 1.2 +/- 0.2 ns, which is >100
      times longer than that in the monomeric GPDI dyad. The transient absorption
      spectrum of G(+*)-PDI(-*) within the GPDI quadruplex suggests the formation of a
      radical anion delocalized over the neighboring PDI units, and this result is
      consistent with the more favorable electrochemical reduction potential for PDIs
      in the quadruplex relative to the monomer. 

PMID- 23978063
TI  - Characteristics of visible fluorescence from ionic liquids.
AB  - The observation of fluorescence in the visible spectral range in imidazolium
      based ionic liquids, in which the peak of the fluorescence spectrum shifts with
      the change in the excitation wavelength by over 200 nm, was reported by Samanta
      and co-workers (Paul et al. J. Phys. Chem. B 2005, 109, 9148; Chem. Phys. Lett.
      2005, 402, 375), and the aggregate structure in the bulk ionic liquid was
      suggested to explain this unique phenomenon. In this work, by employing 2D-scan
      fluorescence spectroscopy, we identified the long- and short-wavelength
      fluorescence components of the fluorescence spectrum of 1-butyl-3
      methylimidazolium tetrafluoroborate ([C4MIM][BF4]), of which only the long
      wavelength fluorescence component was found to be responsible for the reported
      fluorescence properties. The fluorescence intensity of the long-wavelength
      component decreased much faster upon dilution in aqueous mixtures than the short
      wavelength component, supporting the conclusion that the long-wavelength
      fluorescence is from molecular aggregates in the bulk ionic liquid. Fluorescence
      correlation spectroscopy (FCS), which was used to accurately account for the
      number density of the long-wavelength fluorescent species in aqueous solutions of
      the ionic liquid, also suggested that the fluorescence came from aggregate
      structures of molecules in ionic liquids.

PMID- 23978064
TI  - Closing the poor-rich gap in contraceptive use in urban Kenya: are family
      planning programs increasingly reaching the urban poor?
AB  - INTRODUCTION: Kenya is characterized by high unmet need for family planning (FP)
      and high unplanned pregnancy, in a context of urban population explosion and
      increased urban poverty. It witnessed an improvement of its FP and reproductive
      health (RH) indicators in the recent past, after a period of stalled progress.
      The objectives of the paper are to: a) describe inequities in modern
      contraceptive use, types of methods used, and the main sources of contraceptives
      in urban Kenya; b) examine the extent to which differences in contraceptive use
      between the poor and the rich widened or shrank over time; and c) attempt to
      relate these findings to the FP programming context, with a focus on whether the
      services are increasingly reaching the urban poor. METHODS: We use data from the
      1993, 1998, 2003 and 2008/09 Kenya demographic and health survey. Bivariate
      analyses describe the patterns of modern contraceptive use and the types and
      sources of methods used, while multivariate logistic regression models assess how
      the gap between the poor and the rich varied over time. The quantitative analysis
      is complemented by a review on the major FP/RH programs carried out in Kenya.
      RESULTS: There was a dramatic change in contraceptive use between 2003 and
      2008/09 that resulted in virtually no gap between the poor and the rich in
      2008/09, by contrast to the period 1993-1998 during which the improvement in
      contraceptive use did not significantly benefit the urban poor. Indeed, the late
      1990s marked the realization by the Government of Kenya and its development
      partners, of the need to deliberately target the poor with family planning
      services. Most urban women use short-term and less effective methods, with the
      proportion of long-acting method users dropping by half during the review period.
      The proportion of private sector users also declined between 2003 and 2008/09.
      CONCLUSION: The narrowing gap in the recent past between the urban poor and the
      urban rich in the use of modern contraception is undoubtedly good news, which,
      coupled with the review of the family program context, suggests that family
      planning programs may be increasingly reaching the urban poor.

PMID- 23978065
TI  - Acetylated dammarane-type bisdesmosides from Combretum inflatum.
AB  - The first study of the chemical constituents of Combretum inflatum has resulted
      in the isolation of seven new acetylated dammarane-type bisdesmosides (1-7).
      Their structures were determined from microgram quantities on hand using Bruker
      BioSpin TCI 1.7 mm MicroCryoProbe technology, ESIMS, and comparison to data found
      in the literature. Compounds 1-7 were screened for inhibition of an Escherichia
      coli strain UTI89 biofilm, MRSA inhibition, and cytotoxicity in NCI-H460 human
      lung cancer cells. Compounds 3-7 reduced the growth of MRSA at 16 MUg/mL by 71
      45%, and compound 7 had an IC50 value of 3.9 MUM in NCI-H460.

PMID- 23978066
TI  - Helping them stay where they are: status effects on dependency/autonomy-oriented
      helping.
AB  - On the basis of expectation states theory and Weiner's attributional model of
      help giving (Weiner, 1980), we predicted that low-status help seekers would be
      viewed as chronically dependent and their need as due to lack of ability, leading
      to the giving of dependency-oriented help (i.e., full solution to the problem).
      High-status help seekers were expected to be viewed as competent and their
      request as representing their high motivation to overcome a transient difficulty,
      resulting in autonomy-oriented help (i.e., tools to solve the problem). Help
      seeking is viewed as a stigma-consistent behavior that implies weakness when help
      seekers are low-status individuals and as strength when they are high-status
      individuals. Three experiments supported these predictions. The 4th experiment
      indicated that low-status persons who seek autonomy-oriented help are not seen as
      chronically dependent. Implications of these findings for helping and inequality
      are discussed.

PMID- 23978067
TI  - Concern over the misidentification of sexual orientation: social contagion and
      the avoidance of sexual minorities.
AB  - Membership in a valued group can provide an individual with a variety of
      benefits. As a result, people should be motivated to avoid being misidentified as
      a member of an outgroup, particularly a stigmatized outgroup. We argue that when
      group membership is not readily identifiable, concern over potentially being
      mistaken for a member of the outgroup (i.e., social contagion concerns) can be
      potent and can lead to avoidance of the outgroup. The current work shows that
      after controlling for negative attitudes toward homosexuality, social contagion
      concerns independently predict anxiety and avoidance in response to imagined,
      anticipated, and actual contact with a lesbian or gay individual. Results from
      these studies suggest that concern over misclassification of sexual orientation
      is an important and unique predictor of responses to contact with lesbian and gay
      people. Implications for intergroup contact and responses to other stigmatized
      groups are discussed.

PMID- 23978068
TI  - A bidirectional system for the dynamic small molecule control of intracellular
      fusion proteins.
AB  - Small molecule control of intracellular protein levels allows temporal and dose
      dependent regulation of protein function. Recently, we developed a method to
      degrade proteins fused to a mutant dehalogenase (HaloTag2) using small molecule
      hydrophobic tags (HyTs). Here, we introduce a complementary method to stabilize
      the same HaloTag2 fusion proteins, resulting in a unified system allowing
      bidirectional control of cellular protein levels in a temporal and dose-dependent
      manner. From a small molecule screen, we identified N-(3,5-dichloro-2
      ethoxybenzyl)-2H-tetrazol-5-amine as a nanomolar HALoTag2 Stabilizer (HALTS1)
      that reduces the Hsp70:HaloTag2 interaction, thereby preventing HaloTag2
      ubiquitination. Finally, we demonstrate the utility of the HyT/HALTS system in
      probing the physiological role of therapeutic targets by modulating HaloTag2
      fused oncogenic H-Ras, which resulted in either the cessation (HyT) or
      acceleration (HALTS) of cellular transformation. In sum, we present a general
      platform to study protein function, whereby any protein of interest fused to
      HaloTag2 can be either degraded 10-fold or stabilized 5-fold using two
      corresponding compounds. 

PMID- 23978069
TI  - Relationships among serum C-reactive protein, receptor for advanced glycation
      products, metabolic dysfunction, and cognitive impairments.
AB  - BACKGROUND: We examined the clinical value of two serum markers of low-grade
      inflammation, C-reactive protein (CRP) and receptor of advanced glycation
      products (RAGE), as prognostic indices for cognitive decline. METHODS: Patients
      with cognitive impairment (n = 377) and controls (n = 66) were examined by blood
      biochemistry tests, including ELISAs of serum CRP and RAGE, the Mini-mental State
      Examination (MMSE) and Montreal Cognitive Assessment (MoCA), and STEAM 1H-MRS of
      the left hippocampus and thalamus. RESULTS: Compared to the control group, the
      cognitive impairment group was older (63.10 +/- 9.70 years vs. 55.09 +/- 10.77
      years, P = 0.000) and had fewer years of formal education (9.01 +/- 4.01 vs.
      12.94 +/- 3.0, P = 0.000). There were no significant differences in the
      frequencies of type 2 diabetes, hypertension, or hyperlipidemia between groups.
      Serum CRP and RAGE were higher in the cognitive impairment group (CRP: 2.08 mg/L,
      range 1.07 - 3.36 mg/L vs. 0.21 mg/L, range 0.18 - 0.42 mg/L; RAGE: 4.01, range
      2.49 - 5.71, vs. 2.28, range 1.84 - 3.03; P < 0.05 for both). In patients with
      cognitive impairment, there were negative correlations between cognitive function
      (as measured by MMSE and MoCA) and both CRP and RAGE levels (P < 0.05). Patients
      over 55 years exhibited a positive correlation between CRP and myo-inositol peak
      area in the left hippocampus (P < 0.05), while there was no relationship between
      RAGE and any metabolite (P > 0.05). Multiple linear regression revealed that CRP
      was influenced by hypertension (P = 0.026) and cognitive impairment (P = 0.042).
      CONCLUSIONS: Chronic low-grade inflammation is present in patients with cognitive
      impairment. Serum CRP, RAGE, and left hippocampal myo-inositol may provide
      prognostic information on cognitive decline.

PMID- 23978070
TI  - The RNA polymerase factory and archaeal transcription.

PMID- 23978071
TI  - Kinesin spindle protein inhibitors in cancer: a patent review (2008 - present).
AB  - INTRODUCTION: Inhibition of kinesin spindle protein (KSP) has emerged as a novel
      and validated therapeutic strategy against cancers. A lot of new KSP inhibitors
      have been identified in recent years and some of them have entered clinical
      trials. This may provide more selections in future cancer therapy. AREAS COVERED:
      In the present review, the authors will describe the most recent classes of KSP
      inhibitors by reviewing about 96 literatures in which 24 patent applications were
      included from 2008 to now. EXPERT OPINION: Many new KSP inhibitors have been
      discovered that act either by binding in an allosteric site of KSP or by ATP
      competitive inhibition. There are several ATP non-competitive KSP inhibitors
      entering clinical investigation. Although they were both well tolerated and
      showed acceptable pharmacokinetic profiles, limited clinical response was always
      the problem. Mutation of the binding pocket was also a hindrance in the
      development of these allosteric inhibitors. The appearance of ATP competitive KSP
      inhibitors was considered to be able to overcome mutation-mediated resistance to
      the allosteric inhibitors, which could be a new approach for the development of
      novel KSP inhibitors.

PMID- 23978072
TI  - GPI transamidase and GPI anchored proteins: oncogenes and biomarkers for cancer.
AB  - Cancer is second only to heart disease as a cause of death in the US, with a
      further negative economic impact on society. Over the past decade, details have
      emerged which suggest that different glycosylphosphatidylinositol (GPI)-anchored
      proteins are fundamentally involved in a range of cancers. This post
      translational glycolipid modification is introduced into proteins via the action
      of the enzyme GPI transamidase (GPI-T). In 2004, PIG-U, one of the subunits of
      GPI-T, was identified as an oncogene in bladder cancer, offering a direct
      connection between GPI-T and cancer. GPI-T is a membrane-bound, multi-subunit
      enzyme that is poorly understood, due to its structural complexity and membrane
      solubility. This review is divided into three sections. First, we describe our
      current understanding of GPI-T, including what is known about each subunit and
      their roles in the GPI-T reaction. Next, we review the literature connecting GPI
      T to different cancers with an emphasis on the variations in GPI-T subunit over
      expression. Finally, we discuss some of the GPI-anchored proteins known to be
      involved in cancer onset and progression and that serve as potential biomarkers
      for disease-selective therapies. Given that functions for only one of GPI-T's
      subunits have been robustly assigned, the separation between healthy and
      malignant GPI-T activity is poorly defined.

PMID- 23978073
TI  - Football-specific fitness testing: adding value or confirming the evidence?

PMID- 23978074
TI  - Chemical oxidation of dissolved organic matter by chlorine dioxide, chlorine, and
      ozone: effects on its optical and antioxidant properties.
AB  - In water treatment dissolved organic matter (DOM) is typically the major sink for
      chemical oxidants. The resulting changes in DOM, such as its optical properties
      have been measured to follow the oxidation processes. However, such measurements
      contain only limited information on the changes in the oxidation states of and
      the reactive moieties in the DOM. In this study, we used mediated electrochemical
      oxidation to quantify changes in the electron donating capacities (EDCs), and
      hence the redox states, of three different types of DOM during oxidation with
      chlorine dioxide (ClO2), chlorine (as HOCl/OCl(-)), and ozone (O3). Treatment
      with ClO2 and HOCl resulted in comparable and prominent decreases in EDCs, while
      the UV light absorbances of the DOM decreased only slightly. Conversely,
      ozonation resulted in only small decreases of the EDCs but pronounced absorbance
      losses of the DOM. These results suggest that ClO2 and HOCl primarily reacted as
      oxidants by accepting electrons from electron-rich phenolic and hydroquinone
      moieties in the DOM, while O3 reacted via electrophilic addition to aromatic
      moieties, followed by ring cleavage. This study highlights the potential of
      combined EDC-UV measurements to monitor chemical oxidation of DOM, to assess the
      nature of the reactive moieties and to study the underlying reaction pathways. 

PMID- 23978075
TI  - Indentation loading response of a resonance sensor--discriminating prostate
      cancer and normal tissue.
AB  - Prostate cancer is the most common type of cancer among men worldwide. Mechanical
      properties of prostate tissue are promising for distinguishing prostate cancer
      from healthy prostate tissue. The aim was to investigate the indentation loading
      response of a resonance sensor for discriminating prostate cancer tissue from
      normal tissue. Indentation measurements were done on prostate tissue specimens ex
      vivo from 10 patients from radical prostatectomy. The measurement areas were
      analysed using standard histological methods. The stiffness parameter was
      linearly dependent on the loading force (average R(2 )= 0.90) and an increased
      loading force caused a greater stiffness contrast of prostate cancer vs normal
      tissue. The accuracy of the stiffness contrast was assessed by the ROC curve with
      the area under the curve being 0.941 for a loading force of 12.8 mN. The results
      are promising for the development of a resonance sensor instrument for detecting
      prostate cancer.

PMID- 23978076
TI  - Functionalization of small rigid platforms with cyclic RGD peptides for targeting
      tumors overexpressing alphavbeta3-integrins.
AB  - Gadolinium based Small Rigid Plaforms (SRPs) have previously demonstrated their
      efficiency for multimodal imaging and radiosensitization. Since the RGD sequence
      is well-known to be highly selective for alphavbeta3 integrins, a cyclic
      pentapeptide containing the RGD motif (cRGDfK) has been grafted onto the SRP
      surface. An appropriate protocol led to the grafting of two targeting ligands per
      nano-object. The resulting nanoparticles have demonstrated a strong association
      with alphavbeta3 integrins in comparison with cRADfK grafted SRPs as negative
      control. Flow cytometry and fluorescence microscopy have also been used to
      highlight the ability of the nanoparticles to target efficiently HEK293(beta3)
      and U87MG cells. Finally the grafted radiosensitizing nanoparticles were
      intravenously injected into Nude mice bearing subcutaneous U87MG tumors and the
      signal observed by optical imaging was twice as high for SRP-cRGDfK compared to
      their negative analogue. 

PMID- 23978077
TI  - Mitochondrial SIRT5 is present in follicular cells and is altered by reduced
      ovarian reserve and advanced maternal age.
AB  - Women with reduced ovarian reserve or advanced maternal age have an altered
      metabolic follicular microenvironment. As sirtuin 5 (SIRT5) senses cellular
      metabolic state and post-translationally alters protein function, its activity
      may directly impact on oocyte viability and pregnancy outcome. Therefore, we
      investigated the role of SIRT5 in relation to ovarian reserve and maternal age.
      Women (n=47) undergoing routine IVF treatment were recruited and allocated to one
      of three cohorts based on ovarian reserve and maternal age. Surplus follicular
      fluid, granulosa and cumulus cells were collected. SIRT5 mRNA, protein and
      protein activity was confirmed in granulosa and cumulus cells via qPCR,
      immunohistochemistry, western blotting and desuccinylation activity. The presence
      of carbamoyl phosphate synthase I (CPS1), a target of SIRT5, was investigated by
      immunohistochemistry and follicular-fluid ammonium concentrations determined via
      microfluorometry. Women with reduced ovarian reserve or advanced maternal age had
      decreased SIRT5 mRNA, protein and desuccinylation activity in granulosa and
      cumulus cells resulting in an accumulation of follicular-fluid ammonium,
      presumably via alterations in activity of a SIRT5 target, CPS1, which was present
      in granulosa and cumulus cells. This suggests a role for SIRT5 in influencing
      oocyte quality and IVF outcomes. 

PMID- 23978078
TI  - Raman spectroscopic study of temperature and pressure effects on the ionic liquid
      propylammonium nitrate.
AB  - Raman spectroscopy has been used to decipher structural rearrangements in the
      protic ionic liquid propylammonium nitrate, [C3H7NH3][NO3], as a function of
      temperature (180-420 K) at atmospheric pressure and as a function of pressure
      (0.1 MPa-2.0 GPa) at room temperature. Spectral modifications of the Raman bands
      belonging to the anion and cation normal modes indicate structural changes
      occurring in both the polar and nonpolar nanoscale domains of [C3H7NH3][NO3]. The
      crystalline phase of [C3H7NH3][NO3] at low temperature has cations in the anti
      conformation and undertakes a transition with increasing temperature to a phase
      with cations mostly in the gauche conformation. The distorted network of hydrogen
      bonds gives a distribution of local environments around the anions that remains
      in the normal liquid phase at high temperature. The sample under high pressure
      might become microscopically heterogeneous, allowing for micro-Raman imaging of
      different ordered phases of [C3H7NH3][NO3] in a diamond anvil cell. 

PMID- 23978079
TI  - Additional vinyl ketones and their pyranyl ketones in gonyleptid harvestmen
      (Arachnida: Opiliones) suggest these metabolites are widespread in this family.
AB  - Four species of gonyleptid harvestmen, Acanthogonyleptes pulcher, Gonyleptes
      saprophilus (Gonyleptinae), Sodreana barbiellini, and Sodreana leprevosti
      (Sodreaninae), were examined by GC-MS and 13H NMR. All of these species release
      vinyl ketones, and three of them produce the corresponding pyranyl ketones, which
      are presumed hetero-Diels-Alder (HDA) dimers. The vinyl ketones 5-methyl-1-hexen
      3-one, rac-4-methyl-1-hexen-3-one, and (S)-4-methyl-1-hexen-3-one were
      synthesized. Natural 4-methyl-1-hexen-3-one is present as a single stereoisomer
      and has the R-configuration. Vinyl ketone dimers (HDA dimers) were also observed
      in the scent gland exudate and characterized by HRMS, 13C NMR, and 1H NMR
      chemical shifts of the pyranyl moiety.

PMID- 23978081
TI  - Providing culturally competent supervision to trainees with disabilities in
      rehabilitation settings.
AB  - OBJECTIVE: Very little is known about the supervision experiences of psychology
      trainees with disabilities in rehabilitation training settings. It is clear from
      the lack of literature, however, that a gap exists in training and education for
      supervisors about working with disabled trainees and providing culturally
      competent supervision. The purpose of this article is to explore legal and
      ethical concerns, cultural considerations of disability as an aspect of human
      diversity, attitudinal barriers, and mentorship during the professional journey
      of training future psychologists with disabilities. METHOD: This article was
      developed by reviewing the pertinent literature. The authors utilized a sample
      vignette and pertinent points from their own experiences as trainees,
      psychologists, and supervisors with disabilities in rehabilitation settings.
      RESULTS: A thorough discussion of the diversity and cultural aspects of
      supervising disabled trainees is included, along with a discussion of the
      importance of mentorship. IMPLICATIONS: A summary of recommendations is provided
      for supervisors of trainees with disabilities.

PMID- 23978082
TI  - Memory deficits, postconcussive complaints, and posttraumatic stress disorder in
      a volunteer sample of veterans.
AB  - PURPOSE: To better understand how memory impairment is related to postconcussive
      complaints and to posttraumatic stress disorder (PTSD) and whether these
      relationships remain after controlling for premorbid cognitive ability. METHOD:
      We examined memory impairment, premorbid cognitive ability, postconcussive
      complaints, and symptoms of PTSD in 205 veterans, 135 of who gave a self-reported
      history of concussion and exposure to a traumatic life event. We limited our
      sample to those who gave good effort on cognitive testing according to a symptom
      validity measure. RESULTS: Although memory impairment was not associated with a
      history of concussion, it was associated with severity of postconcussive
      complaints. That association was no longer significant after controlling for
      premorbid IQ. A similar analysis yielded slightly different findings for PTSD.
      Memory impairment was associated with PTSD diagnosis, although it was not
      associated with severity of PTSD symptoms after controlling for premorbid
      ability. CONCLUSIONS: These data are consistent with multifactorial models of the
      etiology of postconcussion disorder and PTSD such as the "burden of adversity
      hypothesis" described by Brenner, Vanderploeg, and Terrio (2009). In such models,
      symptom severity and course of recovery are determined not only by trauma
      severity but (also) premorbid risk factors and postonset complications. (PsycINFO
      Database Record (c) 2013 APA, all rights reserved).

PMID- 23978080
TI  - Maternal warm responsiveness and negativity following traumatic brain injury in
      young children.
AB  - PURPOSE/OBJECTIVE: To understand how traumatic brain injury (TBI) affects
      maternal warm responsiveness and negativity over the first 12 months following
      injury. METHOD/DESIGN: We used a concurrent cohort research design to examine
      dyadic interactions in young children with a TBI (n = 78) and a comparison group
      of young children with orthopedic injuries (OI; n = 112) and their families
      during the initial weeks following injury (i.e., baseline) and at two follow-up
      periods (approximately 6 and 12 months later). Trained raters coded videotaped
      interactions during a free play and structured teaching task for maternal warm
      responsiveness and negativity. RESULTS: Mothers in the complicated mild/moderate
      TBI group, but not those in the severe TBI group, exhibited significantly lower
      levels of maternal warm responsiveness than mothers in the OI group. However,
      these differences were observed only at baseline during free play and only at
      baseline and 6 months postinjury during the structured teaching task, suggesting
      diminishing adverse effects of complicated mild/moderate TBI on parenting over
      time postinjury. Analysis failed to reveal group differences in maternal
      negativity at any of the assessments. Across groups, lower socioeconomic status
      (SES) was associated with lower levels of warm responsiveness and higher levels
      of negativity. CONCLUSIONS/IMPLICATIONS: These findings, though preliminary,
      indicate possible alterations in mother-child interactions in the months
      following a TBI.

PMID- 23978083
TI  - Predicting levels of independence with expressing needs and ideas 1 year after
      severe brain injury.
AB  - PURPOSE/OBJECTIVE: Severe brain injury (BI) is a catastrophic event often
      evolving into a complex chronic and severely disabling condition making activity
      participation possible only with sustained caregiving. One aspect of building
      sustainable caregiving is early provision of information about expected outcomes
      germane to patients and their caregivers. An analysis was conducted to determine
      whether 2 levels of independence with expressing needs and ideas 1-year after
      severe BI could be predicted using variables available early after injury.
      METHOD: The authors examined a subsample (n = 79) of participants of an outcome
      study who received repeated neurobehavioral evaluations with the Disorders of
      Consciousness Scale (DOCS) and who were assessed 1 year after injury with the
      Functional Independence Measures (FIM). Explanatory variables included DOCS
      measures, patient characteristics, coexisting conditions, and interventions. The
      outcome is measured with the FIM Expression item. Optimal data analysis was used
      to construct multivariate classification tree models. RESULTS: The 2nd (p = .004)
      DOCS visual measure and seizure (p = .004) entered the final model providing 79%
      accuracy in classifying more or less independence with expressing needs and ideas
      at 1 year. The model will correctly identify 78% of future severe BI survivors
      who will have more independence and 82% of persons who will have less
      independence. CONCLUSIONS: For persons incurring severe BI, it is possible to
      predict, early after injury, more and less independence with expressing needs and
      ideas 1-year after injury. This evidence is 1 contribution to a larger body of
      evidence needed to enable early caregiver education about recovery expectations
      in terms of patient functioning relative to caregiving needs, which in turn will
      help build sustainable caregiving for this population.

PMID- 23978085
TI  - Developing physical activity interventions for adults with spinal cord injury.
      Part 1: a comparison of social cognitions across actors, intenders, and
      nonintenders.
AB  - OBJECTIVE: This article is the first in a three-part series focused on designing
      theory-based interventions to increase leisure time physical activity (LTPA) in
      persons with spinal cord injury (SCI). The purpose of this first study was to
      compare social cognitions for LTPA between people classified as LTPA actors,
      intenders, and nonintenders, as per Schwarzer's Health Action Process Approach
      (HAPA) model. METHOD: Participants were 238 men and women living with a SCI (M
      age = 44.14, SD = 12.74; 44.5% paraplegic) who were subsequently classified as
      LTPA actors (n = 105), intenders (n = 73), or nonintenders (n = 60). Participants
      completed a questionnaire that assessed the following HAPA constructs: LTPA
      outcome expectancies, self-efficacy, intentions, planning, and action control.
      RESULTS: A MANCOVA revealed significant between-groups differences for all
      variables (ps < .001). For all of the measures, actors scored significantly
      higher than intenders who, in turn, scored significantly higher than
      nonintenders. CONCLUSION/IMPLICATIONS: It is both theoretically and practically
      important to distinguish between LTPA nonintenders, intenders, and actors when
      developing LTPA-enhancing interventions for people with SCI. These distinctions
      inform the design and testing of the interventions reported in the two
      accompanying articles.

PMID- 23978086
TI  - Developing physical activity interventions for adults with spinal cord injury.
      Part 2: motivational counseling and peer-mediated interventions for people
      intending to be active.
AB  - OBJECTIVE: The majority of people with spinal cord injury (SCI) do not engage in
      sufficient leisure-time physical activity (LTPA) to attain fitness benefits;
      however, many have good intentions to be active. This paper describes two pilot
      interventions targeting people with SCI who are insufficiently active but intend
      to be active (i.e., "intenders"). METHOD: Study 1 examined the effects of a
      single, telephone-based counseling session on self-regulatory efficacy,
      intentions, and action plans for LTPA among seven men and women with paraplegia
      or tetraplegia. Study 2 examined the effects of a home-based strength-training
      session, delivered by a peer and a fitness trainer, on strength-training task
      self-efficacy, intentions, action plans, and behavior. Participants were 11 men
      and women with paraplegia. RESULTS: The counseling session (Study 1) yielded
      medium- to large-sized increases in participants' confidence to set LTPA goals
      and intentions to be active. The home visit (Study 2) produced medium- to large
      sized increases in task self-efficacy, barrier self-efficacy, intentions, action
      planning, and strength-training behavior from baseline to 4 weeks after the
      visit. CONCLUSIONS/IMPLICATIONS: Study 1 findings provide preliminary evidence
      that a single counseling session can impact key determinants of LTPA among
      intenders with SCI. Study 2 findings demonstrate the potential utility of a peer
      mediated, home-based strength training session for positively influencing social
      cognitions and strength-training behavior. Together, these studies provide
      evidence and resources for intervention strategies to promote LTPA among
      intenders with SCI, a population for whom LTPA interventions and resources are
      scarcely available.

PMID- 23978087
TI  - Developing physical activity interventions for adults with spinal cord injury.
      Part 3: a pilot feasibility study of an intervention to increase self-managed
      physical activity.
AB  - OBJECTIVE: The purpose of this pilot study was to test the efficacy and
      feasibility of a group-mediated cognitive-behavioral training (GMCB) intervention
      for increasing self-managed leisure-time physical activity (LTPA) among people
      with spinal cord injury (SCI) who are already somewhat active. METHODS:
      Participants were 13 members of a supervised exercise program for adults with
      SCI. They took part in a 9-week, evidence-based, theoretically framed, GMCB
      intervention designed to promote self-regulatory skills and to increase the
      amount of time spent in self-managed LTPA, outside of the supervised program.
      Minutes/week of self-managed and supervised LTPA were measured pre- and
      postintervention, along with measures of social-cognitive variables.
      Participants' and the interventionist's perceptions of the intervention were also
      assessed. RESULTS: Participants nearly doubled their total min/week of LTPA, as
      the result of a significant increase in self-managed LTPA from baseline (M =
      42.00 +/- 69.57 min/week) to postintervention (M = 197.50 +/- 270.86 min/week; p
      < .05), at no cost to supervised LTPA. Consistent with the GMCB and counseling of
      self-regulatory skills, self-regulatory efficacy was sustained and action
      planning increased from pre- (M = 4.63 +/- 3.25) to postintervention (M = 6.83 +/
      2.40; p = .06). The intervention materials and protocol were perceived as usable
      by the interventionist and participants and had good intervention fidelity.
      CONCLUSIONS: Persons with SCI can voluntarily increase their self-managed LTPA
      after learning and practicing self-regulatory skills. GMCB training interventions
      are a feasible approach for teaching these skills.

PMID- 23978088
TI  - Correlation between centromere protein-F autoantibodies and cancer analyzed by
      enzyme-linked immunosorbent assay.
AB  - BACKGROUND: Centromere protein-F (CENP-F) is a large nuclear protein of 367 kDa,
      which is involved in multiple mitosis-related events such as proper assembly of
      the kinetochores, stabilization of heterochromatin, chromosome alignment and
      mitotic checkpoint signaling. Several studies have shown a correlation between
      CENP-F and cancer, e.g. the expression of CENP-F has been described to be
      upregulated in cancer cells. Furthermore, several studies have described a
      significant correlation between the expression of autoantibodies to CENP-F and
      cancer. METHODS: Autoantibodies to CENP-F were detected in a small number of
      samples during routine indirect immunofluorescence (IIF) analysis for anti
      nuclear antibodies (ANA) using HEp-2 cells as substrate. Using overlapping
      synthetic peptides covering a predicted structural maintenance of chromosomes
      (SMC) domain, we developed an enzyme-linked immunosorbent assay (ELISA) for
      detection of CENP-F antibodies. RESULTS: Analyzing the reactivity of the sera
      positive in IIF for CENP-F antibodies to overlapping CENP-F peptides, we showed
      that autoantibodies to several peptides correlate with the presence of antibodies
      to CENP-F and a diagnosis of cancer, as increased CENP-F antibody expression
      specific for malignant cancer patients to five peptides was found (A9, A12, A14,
      A16, A27). These antibodies to CENP-F in clinical samples submitted for ANA
      analysis were found to have a positive predictive value for cancer of 50%.
      Furthermore, the expression of cancer-correlated CENP-F antibodies seemed to
      increase as a function of time from diagnosis. CONCLUSION: These results conform
      to previous findings that approximately 50% of those patients clinically tested
      for ANA analyses who express CENP-F antibodies are diagnosed with cancer,
      confirming that these antibodies may function as circulating tumor markers. Thus,
      a peptide-based CENP-F ELISA focused on the SMC domain may aid in identifying
      individuals with a potential cancer.

PMID- 23978089
TI  - The role of kidney in glucose homeostasis--SGLT2 inhibitors, a new approach in
      diabetes treatment.
AB  - The role of the kidney in blood glucose-level regulation was until recently
      underestimated. Renal gluconeogenesis, renal glucose uptake and tubular glucose
      reabsorption are the three ways of renal involvement in glucose homeostasis. In
      the postabsorptive state, 20% of total glucose release is attributed to renal
      gluconeogenesis. Tubular glucose reabsorption is performed by the combined action
      of Na+/D-glucose SGLTs co-transporters and GLUT-facilitated diffusion glucose
      transporters. SGLT2 inhibitors are a new family of agents, which occlude the path
      of SGLT2 glucose reabsorption and cause glucosuria. Efficacy of SGLT2 inhibitors
      includes reduction of HbA1c, fasting and postprandial blood glucose level and
      slight body weight and systolic blood pressure decrease. The most common adverse
      events of them are genital mycotic and urinary tract infections. Dapagliflozin
      and canagliflozin are the first agents of this class, approved from the European
      Medicine Agency and FDA, respectively.

PMID- 23978091
TI  - Cancer odor in the blood of ovarian cancer patients: a retrospective study of
      detection by dogs during treatment, 3 and 6 months afterward.
AB  - BACKGROUND: In recent decades it has been noted that trained dogs can detect
      specific odor molecules emitted by cancer cells. We have shown that the same odor
      can also be detected in the patient's blood with high sensitivity and specificity
      by trained dogs. In the present study, we examined how the ability of dogs to
      detect this smell was affected by treatment to reduce tumor burden, including
      surgery and five courses of chemotherapy. METHODS: In Series I, one drop of
      plasma from each of 42 ovarian cancer patients (taken between the fifth and sixth
      courses of chemotherapy) and 210 samples from healthy controls were examined by
      two trained dogs. All 42 patients in Series I had clinical complete responses,
      all except two had normal CA-125 values and all were declared healthy after
      primary treatment. In Series II, the dogs examined blood taken from a new subset
      of 10 patients at 3 and 6 months after the last (sixth) course of chemotherapy.
      RESULTS: In Series I, the dogs showed high sensitivity (97%) and specificity
      (99%), for detecting viable cancer cells or molecular cancer markers in the
      patients' plasma. Indeed, 29 of 42 patients died within 5 years. In Series II,
      the dogs indicated positive samples from three of the 10 patients at both the 3-
      and 6-month follow-up. All three patients had recurrences, and two died 3-4 years
      after the end of treatment. This was one of the most important findings of this
      study. Seven patients were still alive in January 2013. CONCLUSIONS: Although our
      study was based on a limited number of selected patients, it clearly suggests
      that canine detection gave us a very good assessment of the prognosis of the
      study patients. Being able to detect a marker based on the specific cancer odor
      in the blood would enhance primary diagnosis and enable earlier relapse
      diagnosis, consequently increasing survival.

PMID- 23978093
TI  - Heme oxygenase system and hypertension: a comprehensive insight.
AB  - Hypertension is a complex interplay of interrelated etiologies, and the leading
      risk factor for many cardiovascular morbidity and mortality worldwide. Cardinal
      pathophysiological features of hypertension include enhanced vascular
      inflammation, vascular remodeling, vascular contractility and increased oxidative
      stress. In response to oxidative, inflammatory or other noxious stimuli, many
      physiological pathways like the heme oxygenase (HO) system are activated in an
      attempt to counteract tissue insults. However, the pathophysiological activation
      of the HO system only results to a transient increase of HO activity that fall
      below the necessary threshold capable of activating the downstream signaling
      components of the HO system like the soluble guanylyl cyclase (sGC)/cyclic
      guanosine monophosphate (cGMP) secondary messenger system. Therefore, a more
      robust potentiation of the HO system by pharmacological agents such as hemin,
      heme-arginate, cobalt protoporphyrin or through retroviral HO-1 gene delivery
      would be needed to surmount the threshold for cytoprotection. The HO system
      modulates cellular homeostasis. Importantly, the HO system plays a vital role in
      a wide spectrum of physiologic including the regulation of blood vessel tone.
      Alterations in the activity and expression of HO has been correlated to
      pathophysiology of hypertension and related complications such as hypertrophy,
      myocardial infarction and heart failure. Moreover, the cytoprotection exerted by
      HO is attributable to its catabolic products namely, carbon monoxide,
      bilirubin/biliverdin, and ferritin that are known to modulate immune,
      inflammatory and oxidative insults. The growing incidence of hypertension and
      associated cardiometabolic complications has prompted the need for the
      exploration of alternative therapeutic strategies like substances capable of
      potentiating the HO system. This review briefly, highlights the functional
      significance of the HO system and its downstream signaling molecules including
      bilirubin/biliverdin, carbon monoxide and ferritin as potential therapeutic
      modalities for the management of hypertension and its related co-morbid
      conditions. 

PMID- 23978092
TI  - Complexity generation in fungal polyketide biosynthesis: a spirocycle-forming
      P450 in the concise pathway to the antifungal drug griseofulvin.
AB  - Griseofulvin (1) is a spirocyclic fungal natural product used in treatment of
      fungal dermatophytes. Formation of the spirocycle, or the grisan scaffold, from a
      benzophenone precursor is critical for the activity of 1. In this study, we have
      systematically characterized each of the biosynthetic enzymes related to the
      biogenesis of 1, including the characterization of a new polyketide synthase GsfA
      that synthesizes the benzophenone precursor and a cytochrome P450 GsfF that
      performs oxidative coupling between the orcinol and the phloroglucinol rings to
      yield the grisan structure. Notably, the finding of GsfF is in sharp contrast to
      the copper-dependent dihydrogeodin oxidase that performs a similar reaction in
      the geodin biosynthetic pathway. The biosynthetic knowledge enabled the in vitro
      total biosynthesis of 1 from malonyl-CoA using all purified enzyme components.
      This work therefore completely maps out the previously unresolved enzymology of
      the biosynthesis of a therapeutically relevant natural product. 

PMID- 23978094
TI  - Editorial: cardio-metabolic complications: current perspective and future
      developments.

PMID- 23978096
TI  - Chronic inflammatory diseases and the Acute Respiratory Distress Syndrome (ARDS).
AB  - The Acute Respiratory Distress Syndrome (ARDS) is a highly fatal pro-inflammatory
      oxidative respiratory disease. Relatively recently, the modulating effects of
      chronic inflammatory processes on ARDS susceptibility have been recognized in a
      number of clinical studies. Herein, we briefly review some of the chronic
      conditions that have been reported to increase (cigarette smoking and alcohol
      abuse) or decrease (diabetes and obesity) susceptibility to ARDS. We also propose
      some potential pathways that may hold clues regarding the pathogenesis and/or
      therapy for ARDS. 

PMID- 23978095
TI  - The role of obesity in cardiomyopathy and nephropathy.
AB  - The growing incidence of obesity and related complications such as cardiomyopathy
      and nephropathy remains a global health challenge. Many pathophysiological
      factors including inflammation, oxidative stress and endothelial dysfunction are
      implicated in obesity- induced abnormalities in the heart and kidney. Moreover,
      obesity and nutrient-overload are associated with the activation of different
      inflammatory/oxidative signaling pathways such as endoplasmic reticulum stress,
      nuclear factor-kappaB (NF-kappaB), toll-like-receptor-4 (TLR4) and the renin
      angiotensin-aldosterone system (RAAS). The pathophysiological role of RAAS, TLR4
      and NF-kappaB in perturbing physiological milieu is well acknowledged. Several
      pharmacological agents have been formulated to target one or more of these
      pathways. Although significant strides have been made in elucidating mechanisms
      implicated in obesity-related cardio-renal diseases, much still has to be done.
      The pathophysiology of cardiomyopathy and nephropathy is complex and
      multifaceted. Besides NF-kappa B, TLR4, RAAS and inflammatory mediators such as
      cytokines and chemokines, a wide spectrum of different factors including, the
      environment, diets, lifestyles, genetics and epigenetics are also involved. With
      such multifactorial etiology, it remains a daunting challenge to identify the
      factor(s) that initiate the activation and propagation of adverse stimuli that
      eventually lead to cardiomyopathy and/or nephropathy in obese individuals.
      Similarly, the mechanisms of such activation and propagation should be clearly
      elucidated. Should these hurdles be overcome, there would be a greater likelihood
      for the development of more-effective therapeutic strategies for the prevention,
      treatment and management of obesity-induced cardiomyopathy and nephropathy. The
      present review examines the role of inflammation, oxidative stress and
      endothelial dysfunction in obesity-induced abnormalities in heart and kidney. 

PMID- 23978097
TI  - Metabolic signaling to the central nervous system: routes across the blood brain
      barrier.
AB  - In order to maintain an ideal body weight, an organism must balance energy intake
      with energy expenditure. It is well known that metabolic signals derived in the
      periphery act in well-defined hypothalamic and brainstem neuronal circuits to
      control energy homeostasis. As such, peripheral signals that convey information
      regarding nutritional and metabolic status of the individual must be able to
      access and control these neuronal circuits in order to direct both food intake
      and energy expenditure. Within the hypothalamus, the arcuate nucleus of the
      hypothalamus has become recognized as a critical center in this integrated
      circuitry. Although there is considerable anatomical evidence indicating that the
      arcuate is protected by the blood brain barrier, neurons in this region have been
      repeatedly suggested to directly sense many circulating signals which do not
      readily diffuse across this barrier. In this review we will describe the
      hypothalamic circuitry involved in the regulation of energy homeostasis and will
      discuss data indicating that the arcuate nucleus is, in fact, protected by the
      blood brain barrier. We will then consider alternative mechanisms through which
      one specific circulating adipokine, leptin, can gain access to and influence
      central nervous sites involved in the regulation of energy homeostasis without
      the requirement for direct access from the peripheral circulation to arcuate
      neurons. 

PMID- 23978098
TI  - A critical and comprehensive insight on heme oxygenase and related products
      including carbon monoxide, bilirubin, biliverdin and ferritin in type-1 and type
      2 diabetes.
AB  - The increased prevalence of diabetes and associated complications presents a
      major health risk worldwide, and requires an efficient management protocol. Type
      1 and type-2 diabetes have several common pathophysiological denominators
      including hyperglycemia, elevated oxidative stress, increased inflammation and
      apoptosis. These pathological factors are implicated in the progression and
      worsening of the disease, and the related cardiometabolic complications
      associated with it. Despite the advancement in management of type-1 and type-2
      diabetes, the high incidence of diabetes and related complications calls for
      novel therapeutic strategies. Recent findings suggest that the pharmacological
      modulation of the microsomal heme oxygenase (HO) system may be an important
      therapeutic avenue to explore. The HO system and related products such as carbon
      monoxide, bilirubin, biliverdin, biliverdin reductase and ferritin have been
      shown to abate inflammation, oxidative stress, and apoptosis and reduce
      hyperglycemia. In addition, the HO system also enhances insulin sensitivity and
      increase pancreatic beta cell insulin production in experimental models of type-1
      and type-2 diabetes. This review is an effort to provide evidence of the
      regulatory and cytoprotective role of the HO system in type-1 and type-2
      diabetes, and will highlight the multifaceted mechanisms implicated in the anti
      diabetic effects of the HO system. 

PMID- 23978099
TI  - Flaxseed and endotoxic shock.
AB  - The pathophysiology of endotoxic shock is complex. This review emphasizes the
      role of reactive oxygen species (ROS) in the pathophysiology of endotoxic shock
      and the effectiveness of flaxseed in amelioration of the deleterious effects of
      endotoxic shock on the cardiovascular function and health of the tissue.
      Endotoxic shock is associated with reduction in the cardiac function measured by
      cardiac index and left ventricular work index, cardiac contractility measured by
      dp/dt (rate of change of left ventricular pressure development), dp/dt at
      CPIP/PAW, where CPIP is common peak isovolumetric pressure and PAW is pulmonary
      arterial wedge pressure, arterial pressure, and cellular damage measured by
      increased plasma creatine kinase and elevated plasma lactate. It is also
      accompanied by increases in the generation of ROS by polymorphonuclear
      leukocytes, and cardiac lipid peroxidation product malondialdehyde (MDA) (cardiac
      MDA) and reduction in antioxidant reserve and antioxidant enzyme activity.
      Dimethylthiourea an antioxidant, prevented/reduced the endotoxic shock-induced
      changes in the cardiac function and contractility, arterial pressure, ROS
      generated by polymorphonuclear leucocytes; MDA, antioxidant reserve and
      antioxidant enzyme activity of cardiac tissue, and cellular health. Flaxseed
      which has antioxidant component ameliorated the endotoxic shock-induced changes
      in the cardiac function and contractility, arterial pressure, oxidative stress
      parameters and cellular health. In conclusion, the data suggest that ROS may play
      a role in the pathophysiology of endotoxic shock and that flaxseed, an
      antioxidant may have a role in the treatment of endotoxic shock.

PMID- 23978100
TI  - Synergistic effect of inhibitors of MMPs and ROS-dependent modifications of
      contractile proteins on protection hearts subjected to oxidative stress.
AB  - Cardiac ischemia, followed by reperfusion, often results in the development of
      cardiac contractile dysfunction that limits the recovery prognosis of patients.
      The current goal of pharmacological therapy in the course of ischemic heart
      disease is to improve the oxygen supply/demand ratio for the heart. Cardiac
      contractile proteins such as myosin light chain 1 and 2 (MLC1 and MLC2) and
      troponin I, play a significant role in the regulation of force development. It
      has been shown that MLC1 can be nitrated, S-nitrosylated, as well as
      phosphorylated. These posttranslational modifications (PTMs) of MLC1 are
      associated with an increase in the affinity for the proteolytic enzyme matrix
      metalloproteinase-2 (MMP-2) resulting in an increased degradation of MLC1 that
      corresponds with the development of cardiac contractile dysfunction. The degree
      of MLC1 degradation is associated with the degree of mechanical dysfunction in
      the ischemic heart. Pharmacological regulation of the PTM status of cardiac
      contractile proteins can be achieved by inhibition of phosphorylation, nitration,
      or S-nitrosylation. Most pharmacological approaches for protecting the heart
      against ischemia/reperfusion (I/R) injury are based on the use of a single drug
      at full protective dose, targeting only a single molecular mechanism involved in
      the development of contractile dysfunction. As such, this approach often creates
      side effects associated with interruption of normal physiological processes. It
      is hypothesized that simultaneous pharmacological reduction of reactive oxygen
      species (ROS)-dependent PTMs of contractile proteins such as
      nitration/nitrosylation and/or phosphorylation, together with the pharmacological
      inhibition of the activity of MMPs, will protect the heart from I/R injury
      through synergistic or additive drug effects while also enabling lower doses to
      reduce interruption of normal physiological processes and limit side effects. 

PMID- 23978101
TI  - Effects of a selective histamine H4R antagonist on inflammation in a model of
      carrageenan-induced pleurisy in the rat.
AB  - The histamine H4 receptor (H4R), recently cloned and identified, is a G-protein
      coupled histamine receptor family expressed in immune cells which plays an
      important role in inflammation. Recent data evidentiated that H4R antagonists can
      decrease airway inflammation and hyperreactivity in animal models of asthma. In
      the present study we evaluated the effect of the selective H4R antagonist
      JNJ7777120 (JNJ) in carrageenan-induced pleurisy, an in vivo model of
      inflammation, well characterized for cellular and molecular mechanisms. Intra
      pleural administration of lambda-carrageenan (1% w/v in 0.2 ml sterile saline)
      determined an intense recruitment of leucocytes in pleural exudates and in lung
      tissues, activated inducible nitric oxide (NO) synthase and cyclooxygenase-2,
      thus increasing the generation of harmful autacoids such as NO and pro
      inflammatory prostaglandins, PgE2 and 6-ketoPgF(1alpha), increased cellular and
      DNA oxidative stress, measured as malondialdehyde and 8-OH-deoxyguanosine and the
      local generation of IL-1beta and TNF-alpha. Moreover, the activity of caspase-3,
      an early marker of apoptosis was also activated by lambda-carrageenan injection.
      The pre-treatment with JNJ (5-10 mg Kg-1 b.wt., given intrapleurally), 60 min
      before carrageenan markedly reduced all the studied parameters. This study
      clearly demonstrated that histamine H4R antagonists have anti-inflammatory
      effects and could have potential therapeutic application for the treatment of
      inflammatory diseases.

PMID- 23978102
TI  - The heme oxygenase system and type-1 diabetes.
AB  - Diabetes is a complex endocrine/metabolic disease with many related complications
      including micro-vascular and macrovascular problems such as cardiomyopathy,
      nephropathy, neuropathy and retinopathy. Generally, type-1 diabetes is caused by
      autoimmune- mediated destruction of pancreatic beta cells leading to insulin
      deficiency. This is usually accompanied by dyslipidemia, enhanced hyperglycemia
      mediated oxidative stress, endothelial-cell dysfunction and apoptosis. For
      decades, type-1 diabetes has been traditionally known as insulin-dependent, while
      type-2 as non-insulin dependent diabetes. However, it is becoming increasingly
      clear that insulin deficiency and insulin resistance are manifested in both forms
      of diabetes at different stages. Thus, it may be time revisit the nomenclature
      and adjust it to reflect these observations of insulin deficiency and insulin
      resistance in both forms of diabetes to avoid ambiguity when discussing forms of
      diabetes. Emerging evidence indicates that the heme-oxygenase (HO) system and
      related products including carbon monoxide, ferritin and biliverdin are capable
      of suppressing immune/inflammatory response, and abate oxidative stress and
      apoptosis. More importantly, upregulating the HO-system increases pancreatic beta
      cell insulin release and reduce hyperglycemia in different diabetic models.
      Similarly, carbon monoxide, a product of the HO-catalyzed degradation of heme
      also enhances insulin production and improves glucose metabolism. Since excessive
      immune/inflammatory responses coupled to elevated apoptosis are among the
      cardinal pathophysiological features of type-1 diabetes, this review highlights
      the role of the HO-system and related products such as carbon monoxide and
      bilirubin in the modulation of apoptosis and immune response, and the beneficial
      effects of the HO-system in the pathogenesis of type-1 diabetes and related
      cardiometabolic complications. 

PMID- 23978103
TI  - The heme oxygenase system selectively modulates proteins implicated in
      metabolism, oxidative stress and inflammation in spontaneously hypertensive rats.
AB  - Although recent studies have underscored the role of the heme-oxygenase (HO)
      inducer hemin, on insulin-signaling and glucose metabolism, the underlying
      mechanisms are not completely understood. In this study, two-dimensional-gel
      electrophoresis, massspectrometry and MSACOT-analyses were used to identify and
      characterize novel proteins modulated by hemin in spontaneoushypertensive rat
      (SHR), a model of essential hypertension with insulin resistance/impaired glucose
      metabolism. In addition, the effects of hemin on endothelin-1 (ET-1), protein
      tyrosine-phosphatase-1B (PTP-1B), atrial-natriuretic-peptide (ANP) and its
      surrogate-marker urinary cGMP, and inflammatory cytokines including TNF-alpha, IL
      6 and IL-1beta were investigated. In hemin-treated SHR, several proteins related
      to oxidative-stress and metabolism were modulated. Particularly, hemin enhanced
      aldolase- B, fumarylacetoacetate hydrolase, purine-nucleoside phosphorylase,
      adenosine-kinase, argininosuccinate synthetase and carbonic anhydrase-3 all of
      which are enzymes involved in glucose/energy metabolism and pH homeostasis.
      Similarly, hemin potentiated antioxidant pathways including, NADP(+)-dependant
      isocitrate-dehydrogenase, catalase, glutathione-S-transferase-Yb1 and hsp70, a
      pleiotropic agent that regulates protein-folding, oxidative/pro-inflammatory
      events. Hemin also increased enzymes implicated in cell-growth such as the
      nitrilase-protein-family, but reduced betaine-homocysteine methyltransferase, an
      enzyme associated with insulin resistance and dysfunctional glucose metabolism.
      Furthermore, hemin increased ANP and its surrogate marker, urinary cGMP, but
      reduced ET-1, PTP-1B, TNF-alpha, IL-6, IL-1beta, whereas the HO-inhibitor,
      chromium-mesoporphyrin abolished the effects. The potentiation of ANP, urinary
      cGMP, aldolade-B, fumarylacetoacetate hydrolase, purine-nucleoside phosphorylase,
      adenosine-kinase, argininosuccinate synthetase, carbonic anhydrase-3, hsp70 and
      the corresponding reduction of betaine-homocysteine methyltransferase, PTP-1B,
      TNF-alpha, IL-6, IL-1beta, and ET-1 may be responsible for the improved glucose
      metabolism in hemin-treated animals. Collectively, these findings underscore the
      pleiotropic effects of the HO-system in cellular homeostasis with important roles
      in metabolism and defence. 

PMID- 23978104
TI  - Action and disposition of the beta3-agonist nebivolol in the presence of
      inflammation; an alternative to conventional beta1-blockers.
AB  - Inflammation reduces pharmacological response to beta1-blockers by down
      regulating the target receptor protein. This may contribute to the sub-optimal
      response to pharmacotherapy with beta-blockers. Nebivolol is a third generation
      beta-adrenoceptor (AR) blocker with high selectivity for blocking beta1 and beta3
      agonistic properties. We studied whether response to nebivolol is also reduced by
      inflammation. Male Sprague-Dawley rats (Inflamed; Mycobacterium butyricum
      induced) and Control (healthy) were orally administered single doses of 2 mg/kg
      nebivolol (n=5) or 25 mg/kg propranolol (positive control, n=7-8); ECG recorded
      for PR and RR interval measurements; serial blood samples were collected for
      pharmacokinetic assessment. Subsequently, the myocardial beta1, beta2 and beta3
      AR levels were measured in homogenized hearts. For propranolol, inflammation
      resulted in increased concentration but reduced response and down-regulation of
      beta1- AR. The action and disposition of nebivolol were, however, unaffected by
      inflammation despite the reduced beta1-AR levels. The levels of beta2 and beta3
      AR were unaffected by inflammation. The consistency of response to nebivolol
      despite inflammation may be due to the predominance of contribution of beta2 and
      beta3-AR. The lack of an inhibitory effect of inflammation on the clearance of
      nebivolol is suggestive of mechanisms other than an efficient hepatic metabolism
      for its low bioavailability. If extrapolated to human, nebivolol may be a more
      effective cardiovascular drug when inflammatory conditions are present.

PMID- 23978105
TI  - Targeted gene deletion of prolyl hydroxylase domain protein 3 triggers
      angiogenesis and preserves cardiac function by stabilizing hypoxia inducible
      factor 1 alpha following myocardial infarction.
AB  - The key oxygen sensing molecules, Prolyl-hydroxylase domain 1-3 enzymes (PHD1-3),
      regulate hypoxia-inducible factor (HIF) under hypoxia. In the settings of
      cardiomyopathy and ischemia-reperfusion injury, PHD3 expression is elevated,
      resulting in decreased HIF activation. The role of PHD3 in myocardial injury is
      poorly understood. Hence, we aimed to determine the effects of PHD3 deletion in
      mice on HIF-1alpha and other related pathways following myocardial infarction
      (MI). Left coronary artery (LAD) in both wild type and prolyl hydroxylase 3 knock
      out (PHD3-/-) mice was ligated to induce myocardial infarction. Electrophoretic
      mobility shift analysis showed significant increase in DNA-binding activity of
      HIF-1alpha in PHD3-/- mice as compared to wild type (WT) mice post MI. The PHD3-/
      MI group also showed decreased fibrosis. Seven days after MI, enhanced
      capillary/arteriolar density was observed compared to WTMI group. PHD3-/- mice
      subjected to MI also showed improved cardiac functions (Ejection fraction and
      Fractional shortening), as assessed by echocardiogram, compared to WT. Western
      blot analysis showed increased VEGF, Ang-1 & Bcl-2 expression in PHD3-/-MI group.
      In conclusion, ablation of the PHD3 gene resulted in increased angiogenesis and
      cardiac function after infarction thereby offering a potential target for
      pharmacological management of ischemic myocardial disease.

PMID- 23978106
TI  - Pain catastrophizing as repetitive negative thinking: a development of the
      conceptualization.
AB  - Pain catastrophizing is a well-known concept in the pain literature and has been
      recognized as one of the most powerful psychological determinants of negative
      outcomes for pain problems. However, relatively little effort has been put into
      developing its theoretical underpinnings. More specifically, the intrinsic
      function of catastrophizing is not explicitly dealt with in contemporary
      theoretical models. The aim of this article is to add to existing models by
      proposing a development of the conceptualization of catastrophizing that stresses
      its function as an emotion regulator. We argue that catastrophizing can be
      conceptualized as a form of negative repetitive thinking, which is abstract,
      intrusive, and difficult to disengage from. It has been argued that repetitive
      negative thinking is a form of ineffective problem solving that functions to
      downregulate negative affect and that it can be regarded as an avoidant coping
      strategy because it impedes processing of emotional and somatic responses. Thus,
      in our conceptualization, catastrophizing is proposed to be a form of problem
      solving behavior that functions to reduce negative emotion triggered by pain, and
      other related stimuli. Furthermore, we argue that catastrophizing is preferably
      regarded as a process where cognitions, emotions, and overt behavior are
      intertwined and not viewed as separate entities. To underscore the latter, we
      suggest the term catastrophic worry. Our intention with this development of the
      conceptualization is to give rise to new ideas for research and clinical practice
      and to revitalize discussions about the theoretical framework around pain-related
      catastrophizing. 

PMID- 23978107
TI  - Surviving an abusive supervisor: the joint roles of conscientiousness and coping
      strategies.
AB  - The present study examines a mediated moderation model of the effects of
      conscientiousness and coping strategies on the relationship between abusive
      supervision and employees' job performance. Across 2 studies conducted in India,
      we found evidence that the relationship between abusive supervision and job
      performance was weaker when employees were high in conscientiousness. In
      addition, we found that the use of an avoidance coping strategy facilitated a
      negative relationship between abusive supervision and performance. Finally, we
      found that the moderating effects of conscientiousness were mediated by the use
      of avoidance coping strategies. Our findings contribute to theories of abusive
      supervision, personality, coping strategies, and job performance.

PMID- 23978108
TI  - Enantioselective Gold(I)-catalyzed vinylogous [3 + 2] cycloaddition between
      vinyldiazoacetates and enol ethers.
AB  - The reaction of vinyldiazoacetates with enol ethers catalyzed by the binuclear
      gold complex (R)-DTBMSegphos(AuCl)2 activated by silver hexafluoroantimonate
      results in a highly enantioselective [3 + 2] cycloaddition. The [3 + 2]
      cycloaddition proceeds with dynamic kinetic resolution when the enol ether is a 4
      substituted 1-(methoxymethylene)cyclohexane. The reaction is initiated by
      nucleophilic attack of the vinyl ethers at the vinylogous position of the gold
      vinylcarbene intermediate. 

PMID- 23978109
TI  - Science and football: evaluating the influence of science on performance.
AB  - The scientific study of football has its origins in the early research completed
      in the 1970's. Since these early efforts the available scientific knowledge base
      related to football has developed substantially. The ability of this scientific
      information to influence practice in the day-to-day activity of football
      organisations, especially elite teams, has been largely taken for granted. The
      close examination of this impact can lead to more uncertainty regarding the
      usefulness of the scientific data to the sport. Few articles are available that
      have attempted to critique the link between science and football practice. As
      such, the aims of this article are 2-fold; (i) to examine the historical
      background to "science and football" and to analyse the influence of sports
      science research on the current practice of coaches and practitioners within the
      sport and (ii) to identify potential ways to increase the influence of scientific
      research on practice in the "real world".

PMID- 23978110
TI  - Stimulation of hexachlorocyclohexane (HCH) biodegradation in a full scale in situ
      bioscreen.
AB  - The feasibility of a bioscreen for the in situ biodegradation of HCH and its
      intermediates is demonstrated at a contaminated site in The Netherlands, via the
      discontinuous addition of methanol as electron donor. An infiltration system was
      installed and operated at the site over a length of 150 m and a depth of 8 m, to
      create an anaerobic infiltration zone in which HCH is converted. The construction
      of the infiltration system was combined with the redevelopment of the site.
      During passage through the bioscreen, the concentration of HCH in the groundwater
      decreased from 600 MUg/L to the detection limit of the individual HCH isomers
      (0.01 MUg/L) after one year of operation. The concentration of the intermediate
      biodegradation products benzene and chlorobenzene increased and achieved steady
      state values of respectively 800 and 2700 MUg/L. Benzene and chlorobenzene were
      treated aerobically on site in an existing wastewater treatment plant. By
      changing the infiltration regime, it is conclusively shown that HCH removal is
      the result of the biological degradation and stimulated by the addition of
      methanol as electron donor. To our knowledge, this is the first successful field
      demonstration of the stimulated transformation of HCH to intermediates in a full
      scale anaerobic in situ bioscreen, combined with an aerobic on site treatment to
      harmless end products. 

PMID- 23978111
TI  - Effective electrocatalysis based on Ag2O nanowire arrays supported on a copper
      substrate.
AB  - Silver oxide nanowire arrays (Ag2O NWAs) were first synthesized on a copper (Cu)
      rod by a simple and facile wet-chemistry approach without using any surfactants.
      The as-synthesized Ag2O NWA/Cu rod not only can be used as an integrated
      electrode (called a Ag2O NWA/CRIE) to detect hydrazine (HZ) but also can serve as
      the catalyst layer for a direct HZ fuel cell. The current density of HZ oxidation
      on Ag2O NWA (94.4 mA cm(-2)) is much bigger than that on a bare Cu rod (3.9 mA
      cm(-2)) at -0.6 V, and other Ag2O NWAs have the lowest onset potential (-0.85 V).
      This suggests that a Ag2O NWA integrated electrode has potential application in
      catalytic fields that contain the HZ fuel cell. 

PMID- 23978112
TI  - Reversible biofunctionalization of surfaces with a switchable mutant of avidin.
AB  - Label-free biosensors detect binding of prey molecules ("analytes") to immobile
      bait molecules on the sensing surface. Numerous methods are available for
      immobilization of bait molecules. A convenient option is binding of biotinylated
      bait molecules to streptavidin-functionalized surfaces, or to biotinylated
      surfaces via biotin-avidin-biotin bridges. The goal of this study was to find a
      rapid method for reversible immobilization of biotinylated bait molecules on
      biotinylated sensor chips. The task was to establish a biotin-avidin-biotin
      bridge which was easily cleaved when desired, yet perfectly stable under a wide
      range of measurement conditions. The problem was solved with the avidin mutant
      M96H which contains extra histidine residues at the subunit-subunit interfaces.
      This mutant was bound to a mixed self-assembled monolayer (SAM) containing biotin
      residues on 20% of the oligo(ethylene glycol)-terminated SAM components. Various
      biotinylated bait molecules were bound on top of the immobilized avidin mutant.
      The biotin-avidin-biotin bridge was stable at pH >=3, and it was insensitive to
      sodium dodecyl sulfate (SDS) at neutral pH. Only the combination of citric acid
      (2.5%, pH 2) and SDS (0.25%) caused instantaneous cleavage of the biotin-avidin
      biotin bridge. As a consequence, the biotinylated bait molecules could be
      immobilized and removed as often as desired, the only limit being the time span
      for reproducible chip function when kept in buffer (2-3 weeks at 25  degrees C).
      As expected, the high isolectric pH (pI) of the avidin mutant caused nonspecific
      adsorption of proteins. This problem was solved by acetylation of avidin (to pI <
      5), or by optimization of SAM formation and passivation with biotin-BSA and BSA. 

PMID- 23978113
TI  - [Danish physicians should not contribute to ritual circumcision of underage
      boys].

PMID- 23978114
TI  - [Focus on young patients].

PMID- 23978115
TI  - [Young patients require special attention].
AB  - Approximately 10% of young people suffer from a chronic condition, which can
      affect both the biological, psychological and the social development. Studies
      show that young people appreciate individual consultations with their health-care
      professionals and value information about their legal rights as well as
      confidentiality. Risk-taking behaviour is more frequent among young people with
      chronic conditions than among their healthy peers, and the use of a systematic
      screening tool may help to discuss issues that are relevant to young people.
      Transition from the paediatric to the adult-oriented health-care system needs to
      be planned in due time. 

PMID- 23978116
TI  - [Glycopyrronium bromide is a long-acting inhaled anticholinergic in the treatment
      of severe COPD].
AB  - Long-acting bronchodilators are central in the management of chronic obstructive
      pulmonary disease (COPD). This short review provides an overview of the studies
      evaluating the safety and efficacy of inhaled glycopyrronium, a long-acting
      muscarinic antagonist, in patients with COPD. Glycopyrronium has clinically
      important effects on the level of forced expiratory volume in the first second,
      use of rescue medication, daytime dyspnoea scores, and health status.
      Glycopyrronium also has beneficial effects on dynamic hyperinflation, exercise
      tolerance, and the rate of exacerbations. Glycopyrronium seems to have the
      potential for a significant role in the future management of COPD. 

PMID- 23978117
TI  - [Pharmacotherapy of patients with mild hypertension in primary care].
AB  - Hypertension is an important risk factor for cardiovascular disease. In Denmark,
      patients with hypertension are primarily managed in primary care. A recent
      Cochrane review concluded that pharmacotherapy of patients with mild hypertension
      (systolic blood pressure 140-159 mmHg; diastolic blood pressure 90-99 mmHg; no
      diabetes or cardiovascular disease) did not reduce mortality or morbidity. The
      evidence for pharmacotherapy in patients having mild/uncomplicated hypertension
      is weak. However, current Danish guidelines have taken this into consideration in
      their recommendations of pharmacotherapy to patients with mild/uncomplicated
      hypertension. 

PMID- 23978118
TI  - [The quality of the survey-questionnaire Danish National Survey of Patient
      Experiences is questionable].
AB  - We question the social science methodology in survey-questionnaire Danish
      National Survey of Patient Experiences (LUP). The results from the survey are
      part of the accreditation system in The Danish Health-care Quality Programme
      (DDKM). The methodological validity is researched through LUP-publications. We
      find that LUP has doubtful scientific quality which means that the validity of
      the survey results as such is questionable. Since this has consequences for the
      practical, economic, political and health-care decisions, we recommend that the
      total accreditation programme should be reconsidered. 

PMID- 23978119
TI  - [Improved questionnaire concerning the Danish National Survey of Patient
      Experiences].
AB  - We question the evaluation-design of the Danish National Survey of Patient
      Experiences (LUP). The results from the survey are part of the accreditation
      system in The Danish Health-care Quality Programme. How the evaluation-design may
      be improved is researched through a revised questionnaire tested during a three
      month period. We find that the existing evaluation-model must be replaced by a
      developmental evaluation-approach/model which includes valid measures of patient
      satisfaction, other target-groups, and allows for the context of the specific
      health-care sector. 

PMID- 23978120
TI  - [Palliative surgery of breast cancer].
AB  - Locally advanced breast cancer (stadium III-IV, T3-4) can involve the thoracic
      wall as well as larger skin areas. This may result in symptoms such as pain,
      malodorous wounds, and a reduced quality of life. In some selected cases a
      palliative surgical intervention may be indicated. This case story present two
      cases of locally advanced breast cancer which were managed surgically in a co
      operation between thoracic, plastic and breast cancer surgeons. Both cases were
      preoperatively evaluated at a multidisciplinary team conference. 

PMID- 23978121
TI  - [Intra-abdominal undifferentiated high-grade pleomorphic sarcoma as the cause of
      mechanical bowel obstruction].
AB  - Primary intra-abdominal undifferentiated high-grade pleomorphic sarcoma is rare
      with only 40 cases described worldwide. We describe a case of a patient who
      presented with mechanical bowel obstruction with abdominal undifferentiated high
      grade pleomorphic sarcoma. Five-year survival rates have been reported as low as
      40-55%, especially due to late diagnosis. Rare diagnoses as in our patient
      emphasize the need for close collaboration between pathologists, radiologists and
      surgeons. 

PMID- 23978122
TI  - [Primary manifestation of Chrohn's disease with toxic megacolon in a patient with
      long-time primary sclerosing cholangitis].
AB  - A 38-year-old man with a ten year long history of primary sclerosing cholangitis
      without previous symptoms of inflammatory bowel disease was admitted to hospital
      after a few weeks with abdominal pain, diarrhoea and fever. A computed tomography
      revealed that the colon was dilated to a diameter of 17 cm. Based on a diagnosis
      of toxic megacolon, a subtotal colectomy and an ileostomy were carried out. Gross
      and histological examination showed changes compatible with Crohn's disease. Ten
      years' history of primary sclerosing cholangitis before onset of inflammatory
      bowel disease is very unusual, and toxic colon as the initial symptom of Crohn's
      disease is rare. 

PMID- 23978123
TI  - [Primary localized amyloidosis in nasopharynx and oropharynx].
AB  - Primary localized amyloidosis (PLA) is a rare benign disease defined by the
      presence of extracellular deposits of insoluble amyloid fibrils without systemic
      involvement. We report a case story of a patient with a tumour in pharynx. It was
      excised and based on histopathology the diagnosis PLA was confirmed. The patient
      was examined for systemic amyloidosis (SA). All tests were normal except for an
      elevated lactate dehydrogenase level. Using PET/CT we found a hypermetabolic
      lymph node, but the ultrasound examination was normal. The patient continued
      follow-up and has so far no sign of recurrence of SA. 

PMID- 23978124
TI  - [Foreign body in the hypopharynx].

PMID- 23978125
TI  - Sequence and solvent effects on telomeric DNA bimolecular G-quadruplex folding
      kinetics.
AB  - Telomeric DNA sequences are particularly polymorphic: the adopted structure is
      exquisitely sensitive to the sequence and to the chemical environment, for
      example, solvation. Dehydrating conditions are known to stabilize G-quadruplex
      structures, but information on how solvation influences the individual rates of
      folding and unfolding of G-quadruplexes remains scarce. Here, we used
      electrospray mass spectrometry for the first time to monitor bimolecular G
      quadruplex formation from 12-mer telomeric strands, in the presence of common
      organic cosolvents (methanol, ethanol, isopropanol, and acetonitrile). Based on
      the ammonium ion distribution, the total dimer signal was decomposed into
      contributions from the parallel and antiparallel structures to obtain individual
      reaction rates, and the antiparallel G-quadruplex structure was found to form
      faster than the parallel one. A dimeric reaction intermediate, in rapid
      equilibrium with the single strands, was also identified. Organic cosolvents
      increase the stability of the final structures mainly by increasing the folding
      rates. Our quantitative analysis of reaction rate dependence on cosolvent
      percentage shows that organic cosolvent molecules can be captured or released
      upon G-quadruplex formation, highlighting that they are not inert with DNA. In
      contrast to the folding rates, the G-quadruplex unfolding rates are almost
      insensitive to solvation effects, but are instead governed by the sequence and by
      the final structure: parallel dimers dissociate slower than antiparallel dimers
      only when thymine bases are present at the 5'-end. These results contribute
      unraveling the folding pathways of telomeric G-quadruplexes. The solvent effects
      revealed here enlighten that G-quadruplex structure in dehydrated, and
      molecularly crowded environments are modulated by the nature of cosolvent (e.g.,
      methanol favors antiparallel structures) due to direct interactions, and by the
      time scale of the reaction, with >200-fold acceleration of bimolecular G
      quadruplex formation in the presence of 60% cosolvent. 

PMID- 23978126
TI  - Preclinical and clinical pharmacokinetic/pharmacodynamic considerations for
      antibody-drug conjugates.
AB  - Antibody-drug conjugates (ADCs) represent a promising therapeutic modality for
      the clinical management of cancer. Here we discuss the clinical pharmacology and
      safety of ADCs that are either approved or in late stages of clinical
      development. We have taken examples of ADCs employing either DNA damaging
      payloads (such as calicheamicin) or tubulin depolymerizing agents (such as
      auristatins and maytansinoids) to discuss the impact of dose and dosage intervals
      on pharmacokinetics/pharmacodynamics (PK/PD) and safety of ADCs. We also discuss
      the development of PK/PD models that were validated using preclinical and
      clinical data from two approved ADCs (ado-trastuzumab emtansine (T-DM1,
      KadcylaTM) and brentuximab vedotin (SGN-35, AdcetrisTM). These models could be
      used to predict clinical efficacious doses of ADCs. 

PMID- 23978127
TI  - Lack of association between lipoprotein(a) genetic variants and subsequent
      cardiovascular events in Chinese Han patients with coronary artery disease after
      percutaneous coronary intervention.
AB  - BACKGROUND: Elevated lipoprotein(a) [Lp(a)] levels predict cardiovascular events
      incidence in patients with coronary artery disease (CAD). Genetic variants in the
      rs3798220, rs10455872 and rs6415084 single-nucleotide polymorphisms (SNPs) in the
      Lp(a) gene (LPA) correlate with elevated Lp(a) levels, but whether these SNPs
      have prognostic value for CAD patients is unknown. The present study evaluated
      the association of LPA SNPs with incidence of subsequent cardiovascular events in
      CAD patients after percutaneous coronary intervention (PCI). METHODS: TaqMan SNP
      genotyping assays were performed to detect the rs6415084, rs3798220 and
      rs10455872 genotypes in 517 Chinese Han patients with CAD after PCI. We later
      assessed whether there was an association of these SNPs with incidence of major
      adverse cardiovascular events (MACE: cardiac death, nonfatal myocardial
      infarction, ischemic stroke and coronary revascularization). Serum lipid profiles
      were also determined using biochemical methods. RESULTS: Only the rs6415084
      variant allele was associated with higher Lp(a) levels [41.3 (20.8, 74.6) vs.
      18.6 (10.3, 40.9) mg/dl, p < 0.001]. During a 2-year follow-up period, 102
      patients suffered MACE, and Cox regression analysis demonstrated that elevated
      Lp(a) (>=30 mg/dl) levels correlated with increased MACE (adjusted HR, 1.69; 95%
      CI 1.13-2.53), but there was no association between LPA genetic variants
      (rs6415084 and rs3798220) and MACE incidence (p > 0.05). CONCLUSIONS: Our data
      did not support a relationship between genetic LPA variants (rs6415084 and
      rs3798220) and subsequent cardiovascular events after PCI in Chinese Han CAD
      patients.

PMID- 23978128
TI  - Radiation-induced temporal lobe injury after intensity modulated radiotherapy in
      nasopharyngeal carcinoma patients: a dose-volume-outcome analysis.
AB  - BACKGROUND: To identify the radiation volume effect and significant dosimetric
      parameters for temporal lobe injury (TLI) and determine the radiation dose
      tolerance of the temporal lobe (TL) in nasopharyngeal carcinoma (NPC) patients
      treated with intensity modulated radiation therapy (IMRT). METHODS: Twenty NPC
      patients with magnetic resonance imaging (MRI)-diagnosed unilateral TLI were
      reviewed. Dose-volume data was retrospectively analyzed. RESULTS: Paired samples
      t-tests showed all dosimetric parameters significantly correlated with TLI,
      except the TL volume (TLV) and V75 (the TLV that received >=75 Gy, P = 0.73 and
      0.22, respectively). Receiver operating characteristic (ROC) curves showed V10
      and V20 (P = 0.552 and 0.11, respectively) were the only non-significant
      predictors from V10 to V70 for TLI. D(0.5cc) (dose to 0.5 ml of the TLV) was an
      independent predictor for TLI (P < 0.001) in multivariate analysis; the area
      under the ROC curve for D(0.5cc) was 0.843 (P < 0.001), and the cutoff point 69
      Gy was deemed as the radiation dose limit. The distribution of high dose 'hot
      spot' regions and the location of TLI were consistent. CONCLUSIONS: A D0.5cc of
      69 Gy may be the dose tolerance of the TL. The risk of TLI was highly dependent
      on high dose 'hot spots' in the TL; physicians should be cautious of such 'hot
      spots' in the TL during IMRT treatment plan optimization, review and approval.

PMID- 23978129
TI  - Adherence, expectations and the placebo response: why is good adherence to an
      inert treatment beneficial?
AB  - OBJECTIVE: The current study sought to better understand why good adherence to a
      placebo treatment has been reliably associated with health benefits. We proposed
      a model where initial expectations shape adherence, which then influences
      subsequent expectations that affect placebo response. DESIGN: Seventy-two
      participants were told that they were enrolling in a study of physical activity
      and memory, and were asked to increase their physical activity by 35% for two
      weeks (placebo treatment). MAIN OUTCOME MEASURES: Adherence to this physical
      activity target was measured by pedometer. Expectations and short-term memory
      (free recall) were assessed before and after physical activity. RESULTS: Initial
      expectations predicted adherence to physical activity (r = .27, p < .03), but
      adherence did not predict subsequent expectations (r = .06, p = .60). Testing a
      multi-step meditational model revealed that initial expectations predicted better
      memory even after controlling for adherence, subsequent expectations, baseline
      memory and gender (c' = 1.10, 95% CI = .46-1.74). Stronger expectations for
      memory improvement predicted better memory performance, but adherence and later
      expectations did not mediate this association. CONCLUSIONS: Good adherence to a
      placebo may reflect strong treatment expectations which may convey benefits by
      enhancing the non-specific effects of treatment.

PMID- 23978131
TI  - Alpha,beta-unsaturated diazoketones as versatile building blocks for the
      synthesis of hydroxylated piperidines, indolizidines and quinolizidines.
AB  - A four-step approach for the synthesis of dihydroxylated piperidine,
      quinolizidine and indolizidine systems is described employing alpha,beta
      unsaturated diazoketones as versatile building blocks. Unsaturated diazoketones
      were readily prepared from a Horner-Wadsworth-Emmons reaction between a
      diazophosphonate and amino-aldehydes. The strategy employs an asymmetric
      dihydroxylation reaction as the key step and is simple and straightforward enough
      to be extended to other nitrogen heterocycles.

PMID- 23978130
TI  - Crystallographic fragment screening and structure-based optimization yields a new
      class of influenza endonuclease inhibitors.
AB  - Seasonal and pandemic influenza viruses continue to be a leading global health
      concern. Emerging resistance to the current drugs and the variable efficacy of
      vaccines underscore the need for developing new flu drugs that will be broadly
      effective against wild-type and drug-resistant influenza strains. Here, we report
      the discovery and development of a class of inhibitors targeting the cap
      snatching endonuclease activity of the viral polymerase. A high-resolution
      crystal form of pandemic 2009 H1N1 influenza polymerase acidic protein N-terminal
      endonuclease domain (PAN) was engineered and used for fragment screening leading
      to the identification of new chemical scaffolds binding to the PAN active site
      cleft. During the course of screening, binding of a third metal ion that is
      potentially relevant to endonuclease activity was detected in the active site
      cleft of PAN in the presence of a fragment. Using structure-based optimization,
      we developed a highly potent hydroxypyridinone series of compounds from a
      fragment hit that defines a new mode of chelation to the active site metal ions.
      A compound from the series demonstrating promising enzymatic inhibition in a
      fluorescence-based enzyme assay with an IC50 value of 11 nM was found to have an
      antiviral activity (EC50) of 11 MUM against PR8 H1N1 influenza A in MDCK cells. 

PMID- 23978132
TI  - Cyclopamine, a naturally occurring alkaloid, and its analogues may find wide
      applications in cancer therapy.
AB  - Cyclopamine is a naturally occurring steroidal alkaloid that attenuates the
      Hedgehog signaling pathway by inhibiting the Smoothened receptor. The Hedgehog
      pathway plays an important role in many human cancers. Cyclopamine has served as
      a pivotal tool compound in elucidating the pharmacological effect of the Hedgehog
      signaling pathway, however, due to its poor solubility, stability, and moderate
      activity, its clinical development has been impeded. Significant efforts were
      made to overcome the shortcomings of cyclopamine, giving which results cultivated
      in the identification of IPI- 926, a derivative of cyclopamine, which proceeded
      to clinical trials. 

PMID- 23978133
TI  - Pharmaceutical applications of the benzylisoquinoline alkaloids from Argemone
      mexicana L.
AB  - Argemone mexicana L. (Papaveraceae), accumulates benzylisoquinoline alkaloids,
      (BIA) derived from tyrosine. Although it was originated in the western region of
      the USA-Mexico border, it has spread to tropical and subtropical areas around the
      world. Today, it is used to treat different ailments, given to its antimicrobial,
      antiparasitic, antimalarial, pesticide, cytotoxic and neurological properties.
      These effects are related to the presence of different types of BIA's, such as
      benzophenanthridines (sanguinarine, chelerythrine), protoberberines (berberine)
      and protopines (protopine, allocryptopine). This review covers the historical
      medicinal uses of A. mexicana, as well as its current applications. The chemical
      bases of such effects are discussed in relation to the occurrence of the
      different types of alkaloids. The biochemical process involved in the synthesis
      of these types of alkaloids is also described.

PMID- 23978134
TI  - Recent developments of chiral induction in the syntheses of biologically
      important alkaloids.
AB  - Alkaloids are interesting groups of natural products with important biological
      properties, but naturally available alkaloids are insufficient for biological
      studies. Therefore, the demand for higher amounts of alkaloids made research
      community to synthesize alkaloids by innovative techniques. The importance of
      asymmetric reactions for scientific community to obtain enantiomerically pure
      compounds with good yield and diastereomeric excess (de) or enantiomeric excess
      (ee) by different strategies of asymmetric induction is emphasized in this
      review. In addition, importance have been given to discuss on biologically
      important alkaloids, their skeleton synthesis, intermediates and total synthesis
      with different strategies mainly based on chiral auxiliaries, chiral reagents and
      chiral metal ligand based catalysts. 

PMID- 23978135
TI  - Mitochondria: a promising target for anticancer alkaloids.
AB  - A great number of alkaloids exhibit high potential in cancer research. Some of
      them are anticancer drugs with well-defined clinical uses, exerting their action
      on microtubules dynamics or DNA replication and topology. On the other hand,
      mitochondria have been recognized as an essential organelle in the establishment
      of tumor characteristics, especially the resistance to cell death, high
      proliferative capacity and adaptation to unfavorable cellular environment.
      Interestingly, many alkaloids exert their anticancer activities affecting
      selectively some functions of the tumor mitochondria by 1) modulating OXPHOS and
      ADP/ATP transport, 2) increasing ROS levels and mitochondrial potential
      dissipation by crosstalk between endoplasmic reticulum (ER) and mitochondria, 3)
      inducing mitochondria-dependent apoptosis and autophagy, 4) inhibiting
      mitochondrial metabolic pathways and 5) by alteration of the morphology and
      biogenesis of this organelle. These antecedents show the relevance of developing
      research about the effects of alkaloids on functions controlled by tumor
      mitochondria, offering an attractive target for the design of new alkaloid
      derivatives, considering organelle- specific delivery strategies. This review
      describes mitochondria as a central component in the anticancer action of a set
      of alkaloids, in a way to illustrate the importance of this organelle in
      medicinal chemistry.

PMID- 23978136
TI  - The last decade of antinociceptive alkaloids: structure, synthesis, mechanism of
      action and prospect.
AB  - High molecular diversity of natural products (NPs) can provide a solution for
      many serious medicinal conditions. Frequently attributed with strong and useful
      biological/pharmacological properties, NPs may be directly applied in therapy, or
      could serve as templates for future drugs. As pain is a major symptom in many
      illnesses, and can significantly interfere with a person's quality of life and
      general functioning, pain-killing potential is certainly among the most highly
      valued features of any newly discovered, potentially pharmacologically useful
      molecule. Inspired by the fact that some of the most famous and powerful
      analgesic/antinociceptive agents are natural (plant) alkaloids (e.g. codeine,
      morphine), or are derived from them (oxycodone), herein we have tried to
      systematize recent findings (accumulated during the last decade) on molecular
      structure, mechanism of antinociceptive/analgesic action and synthesis of pain
      killing alkaloids. In other words, this review tries to find out whether it is
      possible to give a general answer to the following questions: Which (new)
      structures are active? How can we obtain them? What do they do to the organism?
      How do they do that (structure-activity relationship)? And what can we do to them
      to make them better (i.e. could they be used as potential leads for new
      antinociceptive drugs)?

PMID- 23978137
TI  - Behavioral effects of 2,3-dihydro- and oxoisoaporphine derivatives in post stroke
      depressive like behavior in male BALB/c mice.
AB  - In this study, antidepressant-like effects of intra-cerebroventricularly
      administration of oxoisoaporphine derivatives in post stroke-depressive like
      behavior were examined through despair swimming and tail suspension models. For
      this aim, acute ischemic stroke was induced by bilateral common carotid arteries
      occlusion which significantly changed the normal behaviors of male balb/c mice.
      We performed stroke-induced anhedonia test as a key result of post
      strokedepressive like behavior by determination of sucrose consumption. Results
      show that some 2,3-dihydro- and oxoisoaporphine derivatives modified the
      abnormality in the behaviors through decreasing in the immobility time in tail
      suspension and despair swimming models and increasing in the swimming and
      climbing times in despair swimming model. We concluded that these alkaloids
      showed antidepressant actions and therefore can be used for treatment of post
      strokedepressive like behavior in acute ischemic stroke patients.

PMID- 23978138
TI  - Structural and mechanistic bases of the anticancer activity of natural
      aporphinoid alkaloids.
AB  - Aporphinoid alkaloids, which encompass a large number of complicated structures,
      are an important group of natural products. The anticancer activity of
      aporphinoid alkaloids has become a hot pharmaceutical research area in recent
      years. Recent studies on the anticancer activity of these compounds are reviewed.
      The structure activity relationships (SARs) and anticancer mechanisms of
      aporphinoid alkaloids, as well as simple aporphine, oxoaporphine,
      dehydroaporphine and dimeric aporphine, have been summarized. The presence of a
      1,2-methylenedioxy group and methylation of nitrogen are key features to the
      cytotoxicity of aporphinoid alkaloids. Oxidation and dehydrogenation of C7 could
      improve the anticancer activity. The contributions of chirality of hydrogen at
      C6a and the substitution pattern of other positions about aporphinoid alkaloids
      for anticancer activity remain unknown. Induced cancer cells apoptosis,
      prevention of cell proliferation, DNA topoisomerase inhibition, reducing the drug
      resistant cellular side population (SP) or cancer stem cells (CSCs) and
      inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase seem to
      play important roles in the molecular mechanisms of anticancer activity about
      aporphinoid alkaloids.

PMID- 23978139
TI  - Alkaloid-metal based anticancer agents.
AB  - In order to overcome the significant side effects and the acquired resistance of
      platinum-based anticancer drugs, great efforts have been devoted to designing new
      platinum compounds or non-platinum transition metal anticancer complexes with
      improved pharmacological properties and a broader range of antitumor activity.
      Among them, the new complexes based on natural alkaloid and their derivatives
      provide a novel approach to potential (pro-)drugs. This review was mainly focused
      on the recent progresses of alkaloid-metal based anticancer agents, including
      metal complexes of natural or synthetic alkaloids, liriodenine, beta-carboline,
      and quinolinoline as anticancer agents, their in vitro anticancer activities and
      primary action mechanism. Additionally, the future development of hybrid alkaloid
      and its derivatives metal complexes as anticancer drugs was discussed, which
      might hold a promise for overcoming multidrug resistance (MDR).

PMID- 23978140
TI  - "Alkaloids in nature: synthesis, isolation and pharmacological applications" part
      1.

PMID- 23978141
TI  - Menthol addition to cigarettes using breakable capsules in the filter. Impact on
      the mainstream smoke yields of the health Canada list constituents.
AB  - Cigarettes with menthol capsules embedded in the filter have been introduced
      recently in many countries. At the same time, concerns have been expressed that
      filter performance could be affected by the crushing of the capsule therein,
      altering mainstream smoke constituent yields, ultimately with the potential to
      impact the toxicity of these products. The present study investigates the
      possible mechanisms underlying differences in smoke constituent deliveries
      following the crushing of a menthol capsule in a cigarette filter. It also
      includes results from a market survey of a selection of commercial cigarette
      brands with menthol capsules representing the different designs for this type of
      product available in different markets worldwide. The yields of 46 Health Canada
      smoke components were determined according to the International Organization for
      Standardization (ISO) machine-smoking regime. Data obtained from measurements
      using cigarettes with the capsule crushed and uncrushed were compared. Except for
      the intended presence of menthol flavors in smoke, no meaningful differences were
      identified in the yields of the remaining measured particulate-phase smoke
      constituents. Regarding the gas-phase smoke constituents, it was found that the
      delivery of lipophilic volatiles was reduced when the capsule was crushed.
      Delivery of the other measured gas-phase components remained unaffected. The
      results from investigations performed in this study did not show any meaningful
      increase in the yield of smoke constituents listed by Health Canada as a result
      of crushing the menthol capsule in the cigarette filter. 

PMID- 23978143
TI  - Role of inferior rectus botulinum toxin injection in vertical strabismus
      resulting from orbital pathology.
AB  - INTRODUCTION: We describe the uses and efficacy of botulinum toxin injection to
      the inferior rectus muscle in vertical strabismus resulting from orbital
      pathology. METHODS: A retrospective review of patients undergoing inferior rectus
      botulinum toxin injection between 1982 and 2006 for vertical strabismus due to
      orbital pathology. RESULTS: There were 13 patients identified; 6 with idiopathic
      orbital inflammatory syndrome (IOIS) including myositis, 3 with previous orbital
      wall fractures, 1 post-optic nerve sheath Schwannoma resection, 1 with lymphoma,
      1 with metastasis, and 1 post-superior ophthalmic vein hemorrhage. A beneficial
      effect with inferior rectus botulinum toxin was obtained in 9/13 (69%) patients
      (mean follow-up 14 months). Resolution or improvement occurred in 4/6 (67%)
      patients with IOIS. Resolution was also obtained in the patient with previous
      optic nerve sheath Schwannoma resection, and the patient who sustained the
      superior ophthalmic vein hemorrhage. Improvement was noted in both the patient
      with lymphoma and in the patient with a metastasis. However, in patients with
      orbital wall fractures, only 1 of 3 patients obtained improvement. Benefit
      appeared independent of the size of vertical deviation, with 4/6 (67%) showing
      improvement with a pre-toxin angle 4-12 PD, and 5/7 (71%) improving with a pre
      toxin angle 16-25 PD. Eleven patients received only 1 injection, one patient
      received 2, and another had an ongoing course of 8 injections. DISCUSSION:
      Vertical strabismus secondary to a range of orbital conditions, particularly
      inflammatory, often can be successfully managed by inferior rectus botulinum
      toxin injections.

PMID- 23978142
TI  - Accommodation and vergence response gains to different near cues characterize
      specific esotropias.
AB  - AIM: To describe preliminary findings of how the profile of the use of blur,
      disparity, and proximal cues varies between non-strabismic groups and those with
      different types of esotropia. DESIGN: This was a case control study. METHODOLOGY:
      A remote haploscopic photorefractor measured simultaneous convergence and
      accommodation to a range of targets containing all combinations of binocular
      disparity, blur, and proximal (looming) cues. Thirteen constant esotropes, 16
      fully accommodative esotropes, and 8 convergence excess esotropes were compared
      with age- and refractive error-matched controls and 27 young adult emmetropic
      controls. All wore full refractive correction if not emmetropic. Response AC/A
      and CA/C ratios were also assessed. RESULTS: Cue use differed between the groups.
      Even esotropes with constant suppression and no binocular vision (BV) responded
      to disparity in cues. The constant esotropes with weak BV showed trends for more
      stable responses and better vergence and accommodation than those without any BV.
      The accommodative esotropes made less use of disparity cues to drive
      accommodation (p = 0.04) and more use of blur to drive vergence (p = 0.008) than
      controls. All esotropic groups failed to show the strong bias for better
      responses to disparity cues found in the controls, with convergence excess
      esotropes favoring blur cues. AC/A and CA/C ratios existed in an inverse
      relationship in the different groups. Accommodative lag of > 1.0 D at 33 cm was
      common (46%) in the pooled esotropia groups compared with 11% in typical children
      (p = 0.05). CONCLUSION: Esotropic children use near cues differently from matched
      non-esotropic children in ways characteristic to their deviations. Relatively
      higher weighting for blur cues was found in accommodative esotropia compared to
      matched controls.

PMID- 23978144
TI  - Expert opinion on best practice guidelines and competency framework for visual
      screening in children.
AB  - PURPOSE: Screening programs to detect visual abnormalities in children vary among
      countries. The aim of this study is to describe experts' perception of best
      practice guidelines and competency framework for visual screening in children.
      METHODS: A qualitative focus group technique was applied during the Portuguese
      national orthoptic congress to obtain the perception of an expert panel of 5
      orthoptists and 2 ophthalmologists with experience in visual screening for
      children (mean age 53.43 years, SD +/- 9.40). The panel received in advance a
      script with the description of three tuning competencies dimensions
      (instrumental, systemic, and interpersonal) for visual screening. The session was
      recorded in video and audio. Qualitative data were analyzed using a categorical
      technique. RESULTS: According to experts' views, six tests (35.29%) have to be
      included in a visual screening: distance visual acuity test, cover test, bi-prism
      or 4/6(Delta) prism, fusion, ocular movements, and refraction. Screening should
      be performed according to the child age before and after 3 years of age (17.65%).
      The expert panel highlighted the influence of the professional experience in the
      application of a screening protocol (23.53%). They also showed concern about the
      false negatives control (23.53%). Instrumental competencies were the most cited
      (54.09%), followed by interpersonal (29.51%) and systemic (16.4%). CONCLUSIONS:
      Orthoptists should have professional experience before starting to apply a
      screening protocol. False negative results are a concern that has to be more
      thoroughly investigated. The proposed framework focuses on core competencies
      highlighted by the expert panel. Competencies programs could be important do
      develop better screening programs.

PMID- 23978145
TI  - Non-linearity of the response accommodative convergence to accommodation ratio.
AB  - PURPOSE: Previous studies have reported variation in stimulus accommodative
      convergence to accommodation (AC/A) ratio across differing accommodative stimuli.
      Response AC/A ratio was assessed across 4 accommodative demands to determine if
      these differences could be due to accommodative inaccuracies to stimuli. METHODS:
      Twenty-three student participants aged 18 to 26 years (mean age 20.3 +/- 1.7
      years) successfully completed all testing conditions. The modified Thorington
      technique was used at 4 m to measure heterophoria. The Shin Nippon SRW 5000
      infrared autorefractor was used to determine accommodative change to -1.50, 
      3.00, -4.50, and -6.00D lens stimuli. RESULTS: Significant differences were found
      in response AC/A ratio between different minus lens stimulated accommodative
      demands (p < 0.001). Mean AC/A ratio values were 3.11 +/- 1.29 with the -1.50D
      lens stimulus; 4.03 +/- 2.11 with -3.00D; 4.14 +/- 1.40 with -4.50D; and 4.48 +/-
      1.56 with -6.00D. No differences in linearity were noted between myopes and non
      myopic participants, but myopes tended to have higher response AC/A ratios than
      non-myopes, mean 4.88 +/- 1.89 for myopes vs 3.61 +/- 1.47 for non-myopes (p =
      0.045). CONCLUSIONS: Response AC/A ratio did not display linearity across 4 minus
      lens accommodative stimuli, but tended to increase with accommodative demand.
      Significant variability in response AC/A ratio was found, both within individuals
      to different accommodative demands, and between individuals across the data set.

PMID- 23978146
TI  - Congenital fibrosis of the extraocular muscles: magnetic resonance imaging
      findings and surgical treatment.
AB  - PURPOSE: We analyzed findings of orbital and cranial magnetic resonance imaging
      (MRI) in patients with congenital fibrosis of the extraocular muscles (CFEOM). We
      described surgery and its outcome. MATERIAL AND METHOD: Nine out of 10 patients
      with clinical findings of CFEOM underwent orbital and cranial MRI to perform a
      study of the extraocular muscles and cranial nerves. A multimodality workstation
      platform developed by the imaging laboratory of our hospital for PC computer
      allowed us to visualize and measure the cross sections of the extraocular muscles
      in a coronal section. Surgery was indicated to resolve strabismus. Outcome was
      considered favorable if the final deviation was < 10 pd in the primary position
      without head turn. RESULTS: In 8 cases (6 males, 5 unilateral [3 left eye]), MRI
      revealed atrophy of at least 1 of the extraocular muscles supplied by the third
      nerve. Five patients had third nerve aplasia or hypoplasia. Clinical findings
      were compatible with a probable diagnosis of CFEOM in all 10 patients. Four
      patients underwent ptosis surgery before being diagnosed with CFEOM. Four
      patients underwent surgery to correct strabismus and, of these, 2 required
      multiple interventions (1 needed 4 interventions). Outcome was successful in only
      2 cases. CONCLUSION: Orbital and cranial MRI provided useful information about
      extraocular muscles and cranial nerves in CFEOM. Surgery must be performed on an
      individual basis; the number of reoperations is high. The outcome of surgery was
      favorable in half of the cases.

PMID- 23978147
TI  - A comparison of referral criteria used by the plusoptiX photoscreener.
AB  - PURPOSE: To evaluate the sensitivity, specificity, and predictive value of 7
      different referral criteria used for the plusoptiX photoscreener on the same
      cohort of children. METHODS: Retrospective chart review of patients presenting to
      a pediatric ophthalmology clinic who underwent plusoptiX photoscreening as part
      of a comprehensive examination. We applied multiple referral criteria from
      previously published studies as well as the manufacturer's criteria in order to
      calculate specificity, sensitivity, and predictive value differences between the
      various referral criteria. We compared all criteria to the results of a pediatric
      ophthalmology examination based upon the 2003 American Association for Pediatric
      Ophthalmology and Strabismus (AAPOS) criteria, as well as the newly accepted
      revision of the AAPOS referral criteria. RESULTS: 109 children were examined with
      a thorough pediatric ophthalmic exam and with the plusoptiX photoscreener. Of
      these, 58 (53%) were confirmed to demonstrate amblyopia risk factors, according
      to 2003 AAPOS criteria. The plusoptiX referral criteria were adjusted to match 7
      different published plusoptiX referral paradigms so that the differing referral
      paradigms could be analyzed for sensitivity and specificity. When comparing the
      differing plusoptiX referral paradigms to 2003 AAPOS criteria, the
      sensitivity/specificity of the 7 different paradigms were respectively:
      Matta/Silbert 98%/80%, Arthur (2) 67%/96%, Arnold 81%/96%, Arthur 81%/92%,
      PediaVision 80%/94%, plusoptiX 98%/41%, AAPOS 74%/86%. When comparing the 7
      differing referral paradigms to the newly approved (2013) AAPOS criteria, the
      sensitivity/specificity were respectively: Matta/Silbert 98%/68%, Arthur (2)
      73%/92%, Arnold 92%/90%, Arthur 86%/85%, PediaVision 90%/92%, plusoptiX 98%/35%,
      AAPOS 87%/87%. CONCLUSION: There are multiple referral criteria available for the
      plusoptiX photoscreener. Screening programs need to evaluate their own
      requirements with respect to desired sensitivity and specificity and decide on
      the most appropriate referral criteria for their program. The "Arnold" criteria
      is the best at maximizing sensitivity and specificity utilizing the 2003 "AAPOS"
      criteria and the "Arnold" and "PediaVision" were best at maximizing sensitivity
      and specificity for the newly accepted AAPOS referral criteria. Screening
      programs will need to decide the level of sensitivity and specificity that they
      wish to obtain, but for most screening programs the "Arnold" criteria may be
      preferred.

PMID- 23978148
TI  - The physiologist Ewald Hering (1834-1918): curriculum vitae.

PMID- 23978149
TI  - Gonadal hormones and voluntary exercise interact to improve discrimination
      ability in a set-shift task.
AB  - Exercise has been demonstrated to improve multiple facets of health, including
      cognitive function. Rodent studies have suggested that exercise has robust
      effects on the hippocampus and on tasks that require the hippocampus. However,
      studies of the effects of exercise in humans often focus on the benefits to
      cognitive processes that engage areas outside of the hippocampus, such as
      executive function. Additionally, when exercise's cognitive benefits are
      examined, consideration of both males and females, and gonadal hormones, is
      rarely made. Here we looked at the interaction of gonadal hormones and exercise
      in terms of the ability of male and female rats to learn to discriminate rewarded
      from unrewarded arms in a T maze based on either brightness (white vs. black) or
      texture (rough vs. smooth) and then to set-shift (a measure of executive
      function), where this required discrimination is based on the opposite dimension.
      Gonadectomized or intact males and females had access to running wheels for 2
      weeks before being tested. Intact males and females given access to unlocked
      running wheels performed better at the initial discrimination (Set 1) compared
      with intact males and females with locked running wheels but not at the set shift
      (Set 2). No advantage of exercise was observed in gonadectomized rats.

PMID- 23978150
TI  - Either main or accessory olfactory system signaling can mediate the rewarding
      effects of estrous female chemosignals in sexually naive male mice.
AB  - A long-held view has been that interest of male mice in female body odors
      reflects an activation of reward circuits in the male brain following their
      detection by the vomeronasal organ (VNO) and processing via the accessory
      olfactory system. We found that adult, sexually naive male mice acquired a
      conditioned place preference (CPP) after repeatedly receiving estrous female
      urine on the nose and being placed in an initially nonpreferred chamber with
      soiled estrous bedding on the floor. CPP was not acquired in control mice that
      received saline on the nose before being placed in a nonpreferred chamber with
      clean bedding. Robust acquisition of a CPP using estrous female odors as the
      reward persisted in separate groups of mice in which VNO-accessory olfactory
      function was disrupted by bilateral lesioning of the accessory olfactory bulb
      (AOB) or in which main olfactory function was disrupted by zinc sulfate lesions
      of the main olfactory epithelium (MOE). By contrast, no CPP was acquired for
      estrous odors in males that received combined AOB and MOE lesions. Either the
      main or the accessory olfactory system suffices to mediate the rewarding effects
      of estrous female odors in the male mouse, even in the absence of prior mating
      experience. The main olfactory system is part of the circuitry that responds to
      chemosignals involved in motivated behavior, a role that may be particularly
      important for humans who lack a functional accessory olfactory system.

PMID- 23978151
TI  - Inactivation of the ventral lateral geniculate and nucleus of the optic tract
      impairs retention of visual eyeblink conditioning.
AB  - Reversible inactivation was used to examine the conditioned stimulus (CS) pathway
      for visual eyeblink conditioning (EBC). Previous research has shown that the
      ventral lateral geniculate (LGNv) and nucleus of the optic tract (NOT) could play
      a role in visual EBC through ipsilateral projections to the medial pontine
      nuclei. Rats were given visual EBC followed by inactivation of the ventral
      lateral geniculate (LGNv), nucleus of the optic tract (NOT), or both nuclei
      contralateral to the conditioned eye. Muscimol infusions into the NOT or LGNv
      impaired retention. Combined inactivation of LGNv/NOT produced the most severe
      impairment. Rats given inactivation of these visual nuclei after training with a
      vibration CS showed no impairment. The findings indicate that a parallel pathway
      of visual CS information projects from the LGNv and NOT to the medial pontine
      nuclei.

PMID- 23978152
TI  - Solid-phase polarization matrixes for dynamic nuclear polarization from
      homogeneously distributed radicals in mesostructured hybrid silica materials.
AB  - Mesoporous hybrid silica-organic materials containing homogeneously distributed
      stable mono- or dinitroxide radicals covalently bound to the silica surface were
      developed as polarization matrixes for solid-state dynamic nuclear polarization
      (DNP) NMR experiments. For TEMPO-containing materials impregnated with water or
      1,1,2,2-tetrachloroethane, enhancement factors of up to 36 were obtained at ~100
      K and 9.4 T without the need for a glass-forming additive. We show that the
      homogeneous radical distribution and the subtle balance between the concentration
      of radical in the material and the fraction of radicals at a sufficient inter
      radical distance to promote the cross-effect are the main determinants for the
      DNP enhancements we obtain. The material, as well as an analogue containing the
      poorly soluble biradical bTUrea, is used as a polarizing matrix for DNP NMR
      experiments of solutions containing alanine and pyruvic acid. The analyte is
      separated from the polarization matrix by simple filtration. 

PMID- 23978153
TI  - Ferroelectric mesocrystals of bismuth sodium titanate: formation mechanism,
      nanostructure, and application to piezoelectric materials.
AB  - Ferroelectric mesocrystals of Bi0.5Na0.5TiO3 (BNT) with [100]-crystal-axis
      orientation were successfully prepared using a topotactic structural
      transformation process from a layered titanate H1.07Ti1.73O4.nH2O (HTO). The
      formation reactions of BNT mesocrystals in HTO-Bi2O3-Na2CO3 and HTO-TiO2-Bi2O3
      Na2CO3 reaction systems and their nanostructures were studied by XRD, FE-SEM,
      TEM, SAED, and EDS, and the reaction mechanisms were given. The BNT mesocrystals
      are formed by a topotactic structural transformation mechanism in the HTO-Bi2O3
      Na2CO3 reaction system and by a combination mechanism of the topotactic
      structural transformation and epitaxial crystal growth in the HTO-TiO2-Bi2O3
      Na2CO3 reaction system, respectively. The BNT mesocrystals prepared by these
      methods are constructed from [100]-oriented BNT nanocrystals. Furthermore, these
      reaction systems were successfully applied to the fabrication of [100]-oriented
      BNT ferroelectric ceramic materials. A BNT ceramic material with a high degree of
      orientation, high relative density, and small grain size was achieved. 

PMID- 23978154
TI  - Genetic polymorphisms of RAD51 and XRCC3 and acute myeloid leukemia risk: a meta
      analysis.
AB  - Studies on gene polymorphisms of RAD51 and X-ray repair cross-complementing group
      3 (XRCC3) and acute myeloid leukemia risk (AML) are conflicting and there is no
      recent meta-analysis. Therefore, the purpose of this study was to evaluate the
      effect of RAD51 G135C and XRCC3 Thr241Met genotypes on AML susceptibility. We
      conducted a systematic search of three databases including PubMed and EMBASE for
      the period up to 20 February 2013 and identified 43 relevant studies. Six
      eligible studies were eventually selected for RAD51 (1764 cases and 3469
      controls) and six studies for XRCC3 (1352 cases and 2582 controls). Pooled odds
      ratios (ORs) and 95% confidence intervals (CIs) for the risk of AML associated
      with RAD51 and XRCC3 were appropriately calculated based on fixed- or random
      effects models. The quality of studies was evaluated using the Newcastle-Ottawa
      Scale (NOS). Subgroup analyses were performed among Asian, Caucasian and other
      populations. The pooled results showed that the leukemia risk was not
      significantly associated with RAD51: the same results were obtained among any
      subgroup analysis. No significant association was demonstrated for AML risk with
      XRCC3 in the total population, but elevated associations were observed in
      Caucasians for the homozygote and recessive comparison (Met/Met vs. Thr/Thr, OR =
      1.67, 95% CI = 1.09-2.57, p = 0.019; recessive model, OR = 1.78, 95% CI = 1.19
      2.65, p = 0.005). This meta-analysis provides evidence that the RAD51 and XRCC3
      polymorphisms are not associated with an increased risk of AML in the total
      population.

PMID- 23978158
TI  - Structural violence and the state: HIV and labour migration from Pakistan to the
      Persian Gulf.
AB  - This paper examines the biopolitics of HIV and labour migration from Pakistan (a
      country classified by UNAIDS as at 'high risk' of a generalised epidemic) to the
      countries of the Gulf Cooperation Council (GCC). The remittances by the labour
      migrants in the Gulf are an invaluable source of foreign exchange for Pakistan
      and a large number of households are entirely dependent upon them. At the same
      time, the National AIDS Control Programme regards Gulf migrants as a key risk
      factor for an HIV epidemic. The majority of HIV positive people in clinics
      comprise Gulf returnee migrants and their family members. This paper suggests
      that in the process of migrating, prospective migrants are subjected to
      structural violence that increases their HIV vulnerabilities. In this process,
      they are subjected to regimes of medical inspection, reduced to their certifiable
      labour power, inscribed with nationalist ideologies identifying HIV as a disease
      that strikes 'the other', and exposed to exploitation that increases their
      vulnerabilities. After migration, they are made to undergo compulsory periodic
      medical examinations in the GCC and, if found to be HIV positive, they are
      forcibly deported without papers, proper diagnosis or healthcare - only to return
      as 'failed subjects'. Taking a disaggregated view of the state, the paper argues
      that, in order to be effective, debates on structural violence and the HIV
      epidemic must make explicit the role of the state in producing migrants'
      vulnerabilities. 

PMID- 23978159
TI  - Self-powered UV-vis photodetector based on ZnIn2S4/hydrogel interface.
AB  - The photosensing properties of vertically aligned ZnIn2S4 nanopetal films grown
      hydrothermally on FTO coated glass are examined without and with surface
      dispensed agarose gel. For the ZnIn2S4 nanopetals photodetector (without gel)
      there is no photoresponse for zero bias. Most interestingly, with surface
      dispensation of agarose gel, the hybrid electronic-iontronic interface system
      shows a strong photoresponse even under zero bias, a highly efficient self
      powered UV-visible light photodetector. Indeed, the zero bias ZnIn2S4/gel hybrid
      photoresponse is a factor of 100 stronger as compared to the response of the only
      ZnIn2S4 device (at -1.5 V bias) and that too without any significant degradation
      in response time. The possible operating mechanisms are proposed. 

PMID- 23978160
TI  - The importance of training strategy adaptation: a learner-oriented approach for
      improving older adults' memory and transfer.
AB  - We investigated the benefits of strategy-adaptation training for promoting
      transfer effects. This learner-oriented approach--which directly encourages the
      learner to generalize strategic behavior to new tasks--helps older adults
      appraise new tasks and adapt trained strategies to them. In Experiment 1, older
      adults in a strategy-adaptation training group used 2 strategies (imagery and
      sentence generation) while practicing 2 tasks (list and associative learning);
      they were then instructed on how to do a simple task analysis to help them adapt
      the trained strategies for 2 different unpracticed tasks (place learning and text
      learning) that were discussed during training. Two additional criterion tasks
      (name-face associative learning and grocery-list learning) were never mentioned
      during training. Two other groups were included: A strategy training group (who
      received strategy training and transfer instructions but not strategy-adaptation
      training) and a waiting-list control group. Both training procedures enhanced
      older adults' performance on the trained tasks and those tasks that were
      discussed during training, but transfer was greatest after strategy-adaptation
      training. Experiment 2 found that strategy-adaptation training conducted via a
      manual that older adults used at home also promoted transfer. These findings
      demonstrate the importance of adopting a learner-oriented approach to promote
      transfer of strategy training.

PMID- 23978161
TI  - Comment on: devices and formulations for pulmonary vaccination.

PMID- 23978162
TI  - Insight into alpha-synuclein plasticity and misfolding from differential micelle
      binding.
AB  - Misfolded species of the 140-residue protein alpha-synuclein (alphaS) are
      implicated in the demise of dopaminergic neurons, resulting in fatal
      neurodegeneration. The intrinsically unstructured protein binds curved synaptic
      vesicle membranes in helical conformations but misfolds into amyloid fibrils via
      beta-sheet interactions. Breaks in helical alphaS conformation may offer a
      pathway to transition from helical to sheet conformation. Here, we explore the
      evolution of broken alphaS helix conformations formed in complex with SDS and
      SLAS micelles by molecular dynamics simulations. The population distribution of
      experimentally observed alphaS conformations is related to the spatial
      concentration of intrinsic micelle shape perturbations. For the success of
      micelle-induced alphaS folding, we posit the length of the first helical segment
      formed, which controls micelle ellipticity, to be a key determinant. The degree
      of micelle curvature relates to the arrangement and segmental motions of helical
      secondary structure elements. A criterion for assessing the reproduction of such
      intermediate time scale protein dynamics is introduced by comparing the sampling
      of experimental and simulated spin label distributions. Finally, at the sites of
      breaks in the elongated, marginally stable alphaS helix, vulnerability to forming
      a transient, intramolecular beta-sheet is identified. Upon subsequent
      intermolecular beta-sheet pairing, pathological alphaS amyloid formation from
      initial helical conformation is thus achievable. 

PMID- 23978164
TI  - Association between family environment and attention deficit hyperactivity
      disorder in children--mothers' and teachers' views.
AB  - BACKGROUND: To ascertain whether factors of the family environment and
      gestational period are associated with the appearance of ADHD in children, as
      reported by various different informants (mothers and teachers). METHODS: This
      paper presents results from the dataset of a longitudinal study to evaluate
      behavioral problems among schoolchildren in Sao Goncalo, Rio de Janeiro State, in
      2005 and 2006. The cross-section considered for this paper comprises records of
      exposure factors and ADHD. In all, 370 schoolchildren of the public school system
      were assessed by 3-stage cluster sampling. The Child Behavior Checklist (CBCL)
      and the Teacher Report Form (TRF) were used to measure outcomes. The exposure
      factors examined were: profile of child and mother, variables relating to the
      family environment, and perinatal considerations. The questions were answered by
      mothers and teachers. A hierarchical logistic regression model was used. RESULTS:
      Precariously functioning families, lack of social support for mothers, adverse
      life events and discord during pregnancy were the factors associated with mother
      reported ADHD. When ADHD was reported by teachers, the variables selected were:
      Intelligence quotient (IQ) and sex, with children with low IQ scores and boys
      more likely to display the disorder. CONCLUSIONS: Assessment of ADHD by teachers
      or mothers reveals specific characteristics that reflect how each of these
      informants understands the children. This highlights the importance of using
      informants from different environments in diagnosing the disorder.

PMID- 23978163
TI  - Transplantation of human cord blood mononuclear cells and umbilical cord-derived
      mesenchymal stem cells in autism.
AB  - BACKGROUND: Autism is a pervasive neurodevelopmental disorder. At present there
      are no defined mechanisms of pathogenesis and therapy is mostly limited to
      behavioral interventions. Stem cell transplantation may offer a unique treatment
      strategy for autism due to immune and neural dysregulation observed in this
      disease. This non-randomized, open-label, single center phase I/II trial
      investigated the safety and efficacy of combined transplantation of human cord
      blood mononuclear cells (CBMNCs) and umbilical cord-derived mesenchymal stem
      cells (UCMSCs) in treating children with autism. METHODS: 37 subjects diagnosed
      with autism were enrolled into this study and divided into three groups: CBMNC
      group (14 subjects, received CBMNC transplantation and rehabilitation therapy),
      Combination group (9 subjects, received both CBMNC and UCMSC transplantation and
      rehabilitation therapy), and Control group (14 subjects, received only
      rehabilitation therapy). Transplantations included four stem cell infusions
      through intravenous and intrathecal injections once a week. Treatment safety was
      evaluated with laboratory examinations and clinical assessment of adverse
      effects. The Childhood Autism Rating Scale (CARS), Clinical Global Impression
      (CGI) scale and Aberrant Behavior Checklist (ABC) were adopted to assess the
      therapeutic efficacy at baseline (pre-treatment) and following treatment.
      RESULTS: There were no significant safety issues related to the treatment and no
      observed severe adverse effects. Statistically significant differences were shown
      on CARS, ABC scores and CGI evaluation in the two treatment groups compared to
      the control at 24 weeks post-treatment (p < 0.05). CONCLUSIONS: Transplantation
      of CBMNCs demonstrated efficacy compared to the control group; however, the
      combination of CBMNCs and UCMSCs showed larger therapeutic effects than the CBMNC
      transplantation alone. There were no safety issues noted during infusion and the
      whole monitoring period. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01343511,
      Title "Safety and Efficacy of Stem Cell Therapy in Patients with Autism".

PMID- 23978165
TI  - Babinet to the half: coupling of solid and inverse plasmonic structures.
AB  - We study the coupling between the plasmonic resonances of solid and inverse
      metallic nanostructures. While the coupling between solid-solid and inverse
      inverse plasmonic structures is well-understood, mixed solid-inverse systems have
      not yet been studied in detail. In particular, it remains unclear whether or not
      an efficient coupling is even possible and which prerequisites have to be met. We
      find that an efficient coupling between inverse and solid resonances is indeed
      possible, identify the necessary geometrical prerequisites, and demonstrate a
      novel solid-inverse plasmonic electromagnetically induced transparency (EIT)
      structure as well as a mixed chiral system. We furthermore show that for the
      coupling of asymmetric rod-shaped inverse and solid structures symmetry breaking
      is crucial. In contrast, highly symmetric structures such as nanodisks and
      nanoholes are straightforward to couple. Our results constitute a significant
      extension of the plasmonic coupling toolkit, and we thus envision the emergence
      of a large number of intriguing novel plasmonic coupling phenomena in mixed solid
      inverse structures. 

PMID- 23978166
TI  - Implementing fluorescence anisotropy screening and crystallographic analysis to
      define PKA isoform-selective activation by cAMP analogs.
AB  - Cyclic AMP (cAMP) is a ubiquitous second messenger that regulates many proteins,
      most notably cAMP-dependent protein kinase (PKA). PKA holoenzymes (comprised of
      two catalytic (C) and two regulatory (R) subunits) regulate a wide variety of
      cellular processes, and its functional diversity is amplified by the presence of
      four R-subunit isoforms, RIalpha, RIbeta, RIIalpha, and RIIbeta. Although these
      isoforms all respond to cAMP, they are functionally nonredundant and exhibit
      different biochemical properties. In order to understand the functional
      differences between these isoforms, we screened cAMP derivatives for their
      ability to selectively activate RI and RII PKA holoenzymes using a fluorescence
      anisotropy assay. Our results indicate that RIalpha holoenzymes are selectively
      activated by C8-substituted analogs and RIIbeta holoenzymes by N6-substituted
      analogs, where HE33 is the most prominent RII activator. We also solved the
      crystal structures of both RIalpha and RIIbeta bound to HE33. The RIIbeta
      structure shows the bulky aliphatic substituent of HE33 is fully encompassed by a
      pocket comprising of hydrophobic residues. RIalpha lacks this hydrophobic lining
      in Domain A, and the side chains are displaced to accommodate the HE33 dipropyl
      groups. Comparison between cAMP-bound structures reveals that RIIbeta, but not
      RIalpha, contains a cavity near the N6 site. This study suggests that the
      selective activation of RII over RI isoforms by N6 analogs is driven by the
      spatial and chemical constraints of Domain A and paves the way for the
      development of potent noncyclic nucleotide activators to specifically target PKA
      iso-holoenyzmes. 

PMID- 23978167
TI  - Negative social preference in relation to internalizing symptoms among children
      with ADHD predominantly inattentive type: girls fare worse than boys.
AB  - Despite distinct peer difficulties, less is known about the peer functioning of
      children with attention-deficit/hyperactivity disorder (ADHD) predominantly
      inattentive type (ADHD-I) in comparison to the peer functioning of children with
      ADHD combined type. Our purpose was to examine whether child sex moderated the
      relations between negative social preference and internalizing/externalizing
      problems in children with ADHD-I. Participants included 188 children diagnosed
      with ADHD-I (110 boys; ages 7-11; 54% Caucasian). Teacher ratings of the
      proportion of classmates who "like/accept" and "dislike/reject" the participating
      child were used to calculate negative social preference scores. Children,
      parents, and teachers provided ratings of anxious and depressive symptoms, and
      parents and teachers provided ratings of externalizing problems. Boys and girls
      did not differ on teachers' negative social preference scores. As hypothesized,
      however, the relation between negative social preference and internalizing
      symptoms was moderated by sex such that negative social preference was
      consistently and more strongly associated with internalizing symptoms among girls
      than in boys. In terms of externalizing problems, negative social preference was
      associated with teacher (but not parent) ratings, yet no moderation by child sex
      was found. Negative social preference is associated with teacher-report of
      externalizing problems for both boys and girls with ADHD-I, whereas negative
      social preference is consistently associated with girls' internalizing symptoms
      across child, parent, and teacher ratings. Implications for future research and
      interventions are discussed. 

PMID- 23978168
TI  - The anti-oxidant properties of isothiocyanates: a review.
AB  - Cruciferous vegetables, such as broccoli and watercress, have been studied
      extensively aiming to evaluate their chemopreventive properties. Some of them
      have already been established using animal models. The ITCs induce Phase II
      enzymes related to detoxification processes of chemical carcinogens to prevent
      the start of carcinogenesis. They also exhibit antitumor activity at post
      initiation phase, suggesting their additional role(s) in cancer prevention.
      Sulforaphane is the most extensively studied isothiocyanate, focused in its anti
      tumoral activity and it is mainly found in great amounts in broccoli and other
      cruciferous. In a dose dependent manner, ITCs inhibit the cell viability of human
      cervical cancer cells, human pancreatic cancer cells, human hepatocellular
      carcinoma cells, human ovarian cancer cells, and have antiinflammatory properties
      in the treatment of human T-cell leukemia cells. This protective effect may be
      due to improved antioxidant status. Although the health effects of diet in humans
      are generally considered promising, there are definite challenges and limitations
      of the current data in better understanding of the molecular mechanisms
      responsible for this effect, together with the possible interactions between
      different dietary constituents. The survey of relevant patents on the use of
      isothiocyanates such as sulforaphane for cancer and cardiovascular diseases
      treatments is also included in this review. 

PMID- 23978169
TI  - Long-term outcomes for the Child STEPs randomized effectiveness trial: a
      comparison of modular and standard treatment designs with usual care.
AB  - OBJECTIVE: This article reports outcomes from the Child STEPs randomized
      effectiveness trial conducted over a 2-year period to gauge the longer term
      impact of protocol design on the effectiveness of evidence-based treatment
      procedures. METHOD: An ethnoracially diverse sample of 174 youths ages 7- 13 (N =
      121 boys) whose primary clinical concerns involved diagnoses or clinical
      elevations related to anxiety, depression, or disruptive behavior were treated by
      community therapists randomly assigned to 1 of 3 conditions: (a) standard, which
      involved the use of 1 or more of 3 manualized evidence-based treatments, (b)
      modular, which involved a single modular protocol (Modular Approach to Treatment
      of Children With Anxiety, Depression, or Conduct Problems; MATCH) having clinical
      procedures similar to the standard condition but flexibly selected and sequenced
      using a guiding clinical algorithm, and (c) usual care. RESULTS: As measured with
      combined Child Behavior Checklist and Youth Self-Report Total Problems,
      Internalizing, and Externalizing scales, the rate of improvement for youths in
      the modular condition was significantly better than for those in usual care. On a
      measure of functional impairment (Brief Impairment Scale), no significant
      differences were found among the 3 conditions. Analysis of service utilization
      also showed no significant differences among conditions, with almost half of
      youths receiving some additional services in the 1st year after beginning
      treatment, and roughly one third of youths in the 2nd year. CONCLUSIONS: Overall,
      these results extend prior findings, supporting incremental benefits of MATCH
      over usual care over a 2-year period.

PMID- 23978170
TI  - AORN efforts to support the IOM report on the future of nursing.

PMID- 23978171
TI  - The Institute of Medicine report on the future of nursing: a transformational
      blueprint.

PMID- 23978172
TI  - Improving communication and building trust.

PMID- 23978173
TI  - The IOM report on the future of nursing: what perioperative nurses need to know.
AB  - The 2010 Institute of Medicine (IOM) report, The Future of Nursing: Leading
      Change, Advancing Health, continues to be the most-viewed report in IOM history.
      Nearly three years after its publication, there are action coalitions of nursing
      and non-nursing agencies in 50 states and the District of Columbia collaborating
      to move the eight recommendations for action forward. There is much work to do to
      reshape health care delivery in the United States, and the IOM has identified
      nurses as key leaders in driving the reform. Every nurse must be educated on the
      key messages of the IOM report and become involved in moving these
      recommendations forward as well as in educating others on what needs to be done.
      AORN and perioperative nurses have a key role in voicing the unique needs of
      perioperative patients and in ensuring that perioperative patient care is
      represented in reform activities. 

PMID- 23978174
TI  - Transforming nursing practice: barriers and solutions.
AB  - All nurses should practice to the full extent of their education and training.
      This key message from the Institute of Medicine report, The Future of Nursing:
      Leading Change, Advancing Health, applies to all RNs. Barriers need to come down
      that prevent nurses from reaching their full potential at a time when the US
      health care system needs to be operating at full capacity. With the focus of US
      health care shifting toward promoting wellness, preventing disease, and managing
      chronic conditions better, the role that nurses play in coordinating care will
      increase. As key members of health care provider teams, nurses' contributions to
      the delivery of safe, high-quality, cost-effective, and patient-centered care
      must be recognized and valued. For nurses to realize their full potential in new
      models of health care delivery, a transformation of nursing practice will need to
      occur. This overview demonstrates how professional nurses should prepare and
      contribute to critical changes needed in health care reform. 

PMID- 23978175
TI  - Perioperative nursing and education: what the IOM future of nursing report tells
      us.
AB  - Changes in the current health care system have rendered the system unprepared to
      support new demands. Similarly, nursing education both before and after licensure
      is no longer adequate. Four of the eight recommendations in the Institute of
      Medicine's Future of Nursing report involve changes to nursing education and pose
      significant goals to achieve. This makes creating innovative ways to meet the
      demand for educating RNs a necessity. This article discusses the Institute of
      Medicine's recommendations, how they relate to perioperative nursing, and ways in
      which nurses and educators can help promote expectations. 

PMID- 23978176
TI  - Partnering to lead change: nurses' role in the redesign of health care.
AB  - Health care has a long-held perception of perioperative nurses as providers who
      advocate for patients and who carry out physician orders. According to the
      Institute of Medicine's 2010 report on the future of nursing, not only must that
      view evolve, but nurses also must play a leading role, in partnership with
      physicians and other health care colleagues, if health care reform is to succeed.
      Several factors will prepare nurses for this new role of partnering to advance
      health, including advancing their formal education, developing leadership as a
      core competency, acquiring leadership skills, and being active in new models of
      leadership (ie, mentorship, volunteering, advocacy). 

PMID- 23978177
TI  - The future of nursing: understanding who nurses are.
AB  - The Institute of Medicine report The Future of Nursing: Leading Change, Advancing
      Health highlights the need for more information about the nursing workforce.
      Without attention to the problem, OR nursing is likely to continue to experience
      the nursing shortage more acutely than other practice areas. By changing how they
      acquire and use nursing data, and by advocating for improved exchange of data
      between federal and state governments and nursing schools, facilities can be
      better prepared for future workforce challenges. 

PMID- 23978178
TI  - The personal and professional impact of the future of nursing report.
AB  - Perioperative nurses can apply the four key messages outlined in the Institute of
      Medicine report The Future of Nursing: Leading Change, Advancing Health from
      personal and professional perspectives. Advocating to remove barriers to practice
      and educating the public about the perioperative nurse's role can help nurses
      practice to the full extent of their education and training. Nurses can achieve
      higher levels of education and training by taking advantage of new educational
      opportunities that offer a more seamless progression to an advanced degree. To
      act as full partners with other health professionals, nurses can participate in
      interdisciplinary teams and implement evidence-based practice, and they can
      contribute to effective workforce planning and policy making by helping to
      collect and analyze data that will improve practice environments. The key
      messages of the report address all nurses, whether they are direct care
      providers, advanced practice RNs, educators, or administrators. 

PMID- 23978179
TI  - Care of patients with multiple sclerosis.

PMID- 23978180
TI  - Hand-held communication devices: friend or foe?

PMID- 23978181
TI  - Checklist implementation for office-based surgery: a team effort.

PMID- 23978183
TI  - Transfer troubles.

PMID- 23978184
TI  - Adopting nursing health record standards.
AB  - The exploratory investigation described in this paper tried to identify and
      acknowledge the added value created by the adoption of nursing practice
      standards. It did so using a case study in a large Portuguese hospital. Following
      a literature review, five assumptions were proposed. Subsequently, a survey was
      developed and administered to a sample of nursing staff at the hospital in
      question. Our results confirmed all but our final assumption, leading to the
      conclusion that the adoption of standards is beneficial to nursing practice. 

PMID- 23978185
TI  - Incorporating rapid neocortical learning of new schema-consistent information
      into complementary learning systems theory.
AB  - The complementary learning systems theory of the roles of hippocampus and
      neocortex (McClelland, McNaughton, & O'Reilly, 1995) holds that the rapid
      integration of arbitrary new information into neocortical structures is avoided
      to prevent catastrophic interference with structured knowledge representations
      stored in synaptic connections among neocortical neurons. Recent studies (Tse et
      al., 2007, 2011) showed that neocortical circuits can rapidly acquire new
      associations that are consistent with prior knowledge. The findings challenge the
      complementary learning systems theory as previously presented. However, new
      simulations extending those reported in McClelland et al. (1995) show that new
      information that is consistent with knowledge previously acquired by a putatively
      cortexlike artificial neural network can be learned rapidly and without
      interfering with existing knowledge; it is when inconsistent new knowledge is
      acquired quickly that catastrophic interference ensues. Several important
      features of the findings of Tse et al. (2007, 2011) are captured in these
      simulations, indicating that the neural network model used in McClelland et al.
      has characteristics in common with neocortical learning mechanisms. An additional
      simulation generalizes beyond the network model previously used, showing how the
      rate of change of cortical connections can depend on prior knowledge in an
      arguably more biologically plausible network architecture. In sum, the findings
      of Tse et al. are fully consistent with the idea that hippocampus and neocortex
      are complementary learning systems. Taken together, these findings and the
      simulations reported here advance our knowledge by bringing out the role of
      consistency of new experience with existing knowledge and demonstrating that the
      rate of change of connections in real and artificial neural networks can be
      strongly prior-knowledge dependent.

PMID- 23978186
TI  - Do framing effects reveal irrational choice?
AB  - Framing effects have long been viewed as compelling evidence of irrationality in
      human decision making, yet that view rests on the questionable assumption that
      numeric quantifiers used to convey the expected values of choice options are
      uniformly interpreted as exact values. Two experiments show that when the
      exactness of such quantifiers is made explicit by the experimenter, framing
      effects vanish. However, when the same quantifiers are given a lower bound (at
      least) meaning, the typical framing effect is found. A 3rd experiment confirmed
      that most people spontaneously interpret the quantifiers in standard framing
      tests as lower bounded and that their interpretations strongly moderate the
      framing effect. Notably, in each experiment, a significant majority of
      participants made rational choices, either choosing the option that maximized
      expected value (i.e., lives saved) or choosing consistently across frames when
      the options were of equal expected value.

PMID- 23978187
TI  - Dissociations in future thinking following hippocampal damage: evidence from
      discounting and time perspective in episodic amnesia.
AB  - Recollecting past experiences and imagining future experiences activate a common
      set of brain regions that includes the hippocampus (Schacter, Addis, & Buckner,
      2007), and both functions are impaired in people with compromised hippocampal
      function (Klein, Loftus, & Kihlstrom, 2002; Tulving, 1985). These findings
      indicate a role for the hippocampus that extends beyond declarative memory.
      However, a case study revealed that a person with extensive medial temporal lobe
      (MTL) damage and episodic amnesia was able to forgo smaller, immediate rewards
      for a larger future payoff to a degree similar to control participants (Kwan et
      al., 2012). This finding suggests that typical regard for the future does not
      depend on hippocampal integrity. To test this hypothesis, the current study
      examined the nature and limits of the role of the hippocampus in future thinking
      and decision making in amnesic individuals with hippocampal damage and associated
      impairments in episodic memory and future imagining. The amnesic individuals were
      administered a delay discounting task to assess valuation of future rewards, a
      probability discounting task to assess risk taking, and the Zimbardo Time
      Perspective Inventory to assess personal orientation toward the past, present,
      and future. Comparisons with demographically matched controls indicated that
      aspects of temporal thought and future-oriented decision making are preserved in
      individuals with hippocampal amnesia despite their inability to imagine
      themselves in detailed future events. Thus, even extensive MTL damage and the
      resulting episodic amnesia do not preclude prudent decision making, including
      consideration of future financial outcomes and personal identification with the
      past and future.

PMID- 23978188
TI  - Solid solutions of Pauli-paramagnetic CaCu3V4O12 and antiferromagnetic
      CaMn3V4O12.
AB  - Solid solutions of Pauli-paramagnetic CaCu3V4O12 and antiferromagnetic CaMn3V4O12
      were prepared by a high-pressure synthesis technique. All samples crystallized in
      the A-site-ordered perovskite structure with isovalent Cu(2+) and Mn(2+) ions at
      the square-planar A' site. The V ion at the B site kept a charge state close to
      +4 in all of the solid solutions, and the electrons of V were delocalized and
      contributed to the metallic properties. The substitution of Mn(2+) for Cu(2+) in
      CaCu3V4O12, where both Cu and V electrons were delocalized, produced the S = 5/2
      localized moments, and the spins at the Mn site interacted antiferromagnetically.
      Spin-glass-like magnetic behaviors due to the random distribution of Cu/Mn ions
      at the A' site were observed at intermediate compositions of the solid solution,
      whereas the antiferromagnetic transition was observed at the end composition
      CaMn3V4O12.

PMID- 23978189
TI  - High-performance light-emitting diodes encapsulated with silica-filled epoxy
      materials.
AB  - Packaging materials have a great impact on the performance and reliability of
      light-emitting diodes (LEDs). In this study, we have prepared high performance
      LED devices through encapsulating LEDs by epoxy materials incorporated with
      filler powders. A set of evaluation methods have also been established to
      characterize the reliability of LED devices. No delamination or internal cracking
      between packaging materials and lead frames has been found for the encapsulated
      high performance LED devices after the package saturation with moisture and
      subsequent exposure to high-temperature solder reflow and thermal cycling. Four
      kinds of inorganic silica fillers, namely, quartz, fused silica, cristobalite,
      and spherical silica, and one kind of organic filler, that is, spherical silicone
      powder, were incorporated into the epoxy packaging materials to compare their
      effects on performance of LED devices. The properties of epoxy packaging
      materials and LED devices were studied by differential scanning calorimetry
      (DSC), thermogravimetric analyses (TGA), dynamic mechanical analysis (DMA),
      thermomechanical analyzer (TMA), ultravioletvisible spectrophotometer (UV-vis),
      scanning acoustic microscopy (SAM), and scanning electron microscopy (SEM).
      Except the spherical silicone powder filled epoxy materials, all the other filled
      systems showed lower equilibrium water sorption content and smaller water
      diffusion coefficient in both water sorption and moisture sorption tests. The
      coefficient of thermal expansion (CTE) values were also decreased with the
      addition of fillers, and the systems filled with quartz, fused, and filled with
      spherical silica gave the best performance, which exhibited the reduced CTE
      values both below and above Tg. The results of TGA essentially showed no
      difference between filled and unfilled systems. The glass transition temperature
      changed little for all the filled systems, except the one incorporated with
      spherical silicone. The modulus at room temperature increased with the addition
      of fillers. The light transmittance of filled epoxy materials varied with fillers
      after UV and thermal aging. 

PMID- 23978190
TI  - Automated digital microfluidic platform for magnetic-particle-based immunoassays
      with optimization by design of experiments.
AB  - We introduce an automated digital microfluidic (DMF) platform capable of
      performing immunoassays from sample to analysis with minimal manual intervention.
      This platform features (a) a 90 Pogo pin interface for digital microfluidic
      control, (b) an integrated (and motorized) photomultiplier tube for
      chemiluminescent detection, and (c) a magnetic lens assembly which focuses
      magnetic fields into a narrow region on the surface of the DMF device,
      facilitating up to eight simultaneous digital microfluidic magnetic separations.
      The new platform was used to implement a three-level full factorial design of
      experiments (DOE) optimization for thyroid-stimulating hormone immunoassays,
      varying (1) the analyte concentration, (2) the sample incubation time, and (3)
      the sample volume, resulting in an optimized protocol that reduced the detection
      limit and sample incubation time by up to 5-fold and 2-fold, respectively,
      relative to those from previous work. To our knowledge, this is the first report
      of a DOE optimization for immunoassays in a microfluidic system of any format. We
      propose that this new platform paves the way for a benchtop tool that is useful
      for implementing immunoassays in near-patient settings, including community
      hospitals, physicians' offices, and small clinical laboratories. 

PMID- 23978191
TI  - Switchable fluorescent imaging of intracellular telomerase activity using
      telomerase-responsive mesoporous silica nanoparticle.
AB  - This work designs a telomerase-responsive mesoporous silica nanoparticle (MSN) to
      realize in situ "off-on" imaging of intracellular telomerase activity. In the
      wrapping DNA (O1) sealed MSN probe, a black hole fluorescence quencher is
      covalently immobilized on the inner walls of the mesopores, while fluorescein is
      loaded in the mesopores. In the presence of telomerase and dNTPs, the designed O1
      can be extended and then moves away from the MSN surface via forming a rigid
      hairpin-like DNA structure. Thus the O1 can act as a "biogate" to block and
      release fluorescein for "off-on" switchable fluorescent imaging. The MSN probe
      exhibits good performance for sensitive in situ tracking of telomerase activity
      in living cells. The practicality of this protocol has been verified by
      monitoring the change of cellular telomerase activity in response to telomerase
      related drugs. 

PMID- 23978193
TI  - Nutritional supplements for diabetes sold on the internet: business or health
      promotion?
AB  - BACKGROUND: Diabetes is one of the most widespread chronic disease. Although many
      medications are available for the treatment and prevention of diabetes, many
      people turn to nutritional supplements (NSs). In these years, the online sales
      have contributed to the growth of use of nutritional supplement. The aim of the
      research was to investigate the type of information provided by sales websites on
      NSs, and analyse the existence of scientific evidence about some of the most
      common ingredients found in available NSs for diabetes. METHODS: A web search was
      conducted in April 2012 to identify web sites selling NSs in the treatment of
      diabetes using Google, Yahoo and Bing! and the key word used was "diabetes
      nutritional supplements". Website content was evaluated for the quality of
      information available to consumers and for the presence of a complete list of
      ingredients in the first NS suggested by the site. Subsequently, in order to
      analyze the scientific evidence on the efficacy of these supplements a PubMed
      search was carried out on the ingredients that were shared in at least 3
      nutritional supplements. RESULTS: A total of 10 websites selling NSs were
      selected. Only half of the websites had a Food and Drug Administration disclaimer
      and 40% declared clearly that the NS offered was not a substitute for proper
      medication. A total of 10 NS ingredients were searched for on PubMed. Systematic
      reviews, meta-analyses or randomized control trials were present for all the
      ingredients except one. Most of the studies, however, were of poor quality and/or
      the results were conflicting. CONCLUSIONS: Easy internet access to NSs lacking in
      adequate medical information and strong scientific evidence is a matter of public
      health concern, mainly considering that a misleading information could lead to an
      improper prevention both in healthy people and people suffering from diabetes.
      There is a clear need for more trials to assess the efficacy and safety of these
      NSs, better quality control of websites, more informed physicians and greater
      public awareness of these widely used products.

PMID- 23978195
TI  - Fine spatiotemporal control of nitric oxide release by infrared pulse-laser
      irradiation of a photolabile donor.
AB  - Two-photon-excitation release of nitric oxide (NO) from our recently synthesized
      photolabile NO donor, Flu-DNB, was confirmed to allow fine spatial and temporal
      control of NO release at the subcellular level in vitro. We then evaluated in
      vivo applications. Femtosecond near-infrared pulse laser irradiation of
      predefined regions of interest in living mouse brain treated with Flu-DNB induced
      NO-release-dependent, transient vasodilation specifically at the irradiated site.
      Photoirradiation in the absence of Flu-DNB had no effect. Further, NO release
      from Flu-DNB by pulse laser irradiation was shown to cause chemoattraction of
      microglial processes to the irradiated area in living mouse brain. To our
      knowledge, this is the first demonstration of induction of biological responses
      in vitro and in vivo by means of precisely controlled, two-photon-mediated
      release of NO. 

PMID- 23978194
TI  - In an in vitro model of human tuberculosis, monocyte-microglial networks regulate
      matrix metalloproteinase-1 and -3 gene expression and secretion via a p38 mitogen
      activated protein kinase-dependent pathway.
AB  - BACKGROUND: Tuberculosis (TB) of the central nervous system (CNS) is
      characterized by extensive tissue inflammation, driven by molecules that cleave
      extracellular matrix such as matrix metalloproteinase (MMP)-1 and MMP-3. However,
      relatively little is known about the regulation of these MMPs in the CNS.
      METHODS: Using a cellular model of CNS TB, we stimulated a human microglial cell
      line (CHME3) with conditioned medium from Mycobacterium tuberculosis-infected
      primary human monocytes (CoMTb). MMP-1 and MMP-3 secretion was detected using
      ELISAs confirmed with casein zymography or western blotting. Key results of a
      phospho-array profile that detects a wide range of kinase activity were confirmed
      with phospho-Western blotting. Chemical inhibition (SB203580) of microglial cells
      allowed investigation of expression and secretion of MMP-1 and MMP-3. Finally we
      used promoter reporter assays employing full length and MMP-3 promoter deletion
      constructs. Student's t-test was used for comparison of continuous variables and
      multiple intervention experiments were compared by one-way ANOVA with Tukey's
      correction for multiple pairwise comparisons. RESULTS: CoMTb up-regulated
      microglial MMP-1 and MMP-3 secretion in a dose- and time-dependent manner. The
      phospho-array profiling showed that the major increase in kinase activity due to
      CoMTb stimulation was in p38 mitogen activated protein kinase (MAPK), principally
      the alpha and gamma subunits. p38 phosphorylation was detected at 15 minutes,
      with a second peak of activity at 120 minutes. High basal extracellular signal
      regulated kinase activity was further increased by CoMTb. Secretion and
      expression of MMP-1 and MMP-3 were both p38 dependent. CoMTb stimulation of full
      length and MMP-3 promoter deletion constructs demonstrated up-regulation of
      activity in the wild type but a suppression site between -2183 and -1612 bp.
      CONCLUSIONS: Monocyte-microglial network-dependent MMP-1 and MMP-3 gene
      expression and secretion are dependent upon p38 MAPK in tuberculosis. p38 is
      therefore a potential target for adjuvant therapy in CNS TB.

PMID- 23978196
TI  - Metformin: an old drug with new potential.
AB  - Metformin is the most commonly prescribed antidiabetic oral agent. It has also
      been used off-label for polycystic ovarian syndrome, steatohepatitis, and HIV
      associated metabolic abnormalities. However, this oldie is a newbie for the
      oncologist. Population studies have suggested that metformin decreased the
      incidence and mortality rates of cancer in diabetic patients. With better
      understanding of its mechanisms of antitumor activity, metformin may become a new
      drug for cancer in combination with chemotherapy or targeted therapy. 

PMID- 23978197
TI  - Longitudinal effects of sibling relationship quality on adolescent problem
      behavior: a cross-ethnic comparison.
AB  - The aim of the present study was to examine whether adolescents of Moroccan and
      Dutch origin differ concerning sibling relationship quality and to examine
      whether the associations between quality of the sibling relationship and level
      and change in externalizing and internalizing problem behavior are comparable for
      Moroccan and Dutch adolescents. Five annual waves of questionnaire data on
      sibling support and conflict as well as externalizing problems, anxiety and
      depression were collected from 159 ethnic Moroccan adolescents (Mage = 13.3
      years) and from 159 ethnic Dutch adolescents (Mage = 13.0 years). Our findings
      demonstrated significant mean level differences between the Moroccan and Dutch
      sample in sibling relationship quality, externalizing problems, and depression,
      with Moroccan adolescents reporting higher sibling relationship quality and less
      problem behavior. However, effects of sibling relationship quality on
      externalizing problems, anxiety, and depression were similar for the Moroccan and
      Dutch samples. Sibling support was not related to level of externalizing
      problems, nor to changes in externalizing problems, anxiety, and depression.
      Additionally, more sibling conflict was related to a higher starting level of and
      faster decreases in problem behaviors. Our results support the ethnic equivalence
      model, which holds that the influence of family relationships is similar for
      different ethnic groups. Moreover, sibling support and conflict affect both the
      level and the fluctuations in problem behavior over time in specific ethnic
      groups similarly. Implications for future studies and interventions are
      subsequently discussed.

PMID- 23978199
TI  - Weekday and weekend physical activity patterns of French and Spanish adolescents.
AB  - Adolescents' objectively assessed physical activity (PA) patterns during specific
      segments of the day remain unclear. In order to develop a clearer understanding
      this study examined country and gender differences in moderate to vigorous
      physical activity (MVPA) levels during specific segments of weekdays and weekend
      days, and explored the contribution of each segment to PA guidelines. Morpho
      demographic, socio-economic and PA data were collected from a sample of 829
      French and Spanish adolescents (45.0% Spanish; 55.2% females; 14.33+/-.73 years).
      Actigraph GT3X accelerometers were worn for seven days to assess adolescents'
      MVPA for three segments of weekdays (school-travel-time, school-time, and non
      school-time), and weekend days (morning-time, afternoon-time and night-time).
      Data were analysed using multilevel modelling. The most active segments were non
      school-time (29.2+/-17.5 min) and school-time (25.8+/-14.2 min) during weekdays,
      and morning-time (28.2+/-25.8 min) on weekend days. Except for school-time,
      Spanish adolescents were more significantly active than French adolescents during
      all segments. Significant gender differences were found in all segments. Country
      differences highlight the need to recognise cultural contexts that influence
      adolescents' PA. Common European-wide strategies may be insufficient to increase
      MVPA levels if cultural variability is not considered. Spanish and French PA
      intervention programmes should target girls and low-active boys during non-school
      time and weekends.

PMID- 23978198
TI  - Psychological distress in young adults exposed to war-related trauma in
      childhood.
AB  - We tested a conceptual model of the effect of war-trauma exposure in childhood on
      psychological distress in young adulthood. Participants included 151 urban
      Kuwaiti children (51% female; M age = 10.62 years) exposed to the 1990-1991 Gulf
      crisis (assessed in 1993); participants also included 140 parents (81% female; M
      age mothers = 36.50 years; M age fathers = 41 years). In 2003, 120 participants
      were reassessed as young adults (50% female; M age = 21.19 years). The conceptual
      model was evaluated with structural equations. War-trauma exposure was associated
      with psychological distress in children and parents, but parents reported larger
      effects than children. Parents' psychological distress did not contribute to
      children's psychological distress. Children's psychological distress did not
      dissipate over time. Social support may function as a potential mediator of the
      effect of war-trauma exposure on psychological distress. Findings support the
      importance of early detection and treatment of children exposed to war trauma.
      Findings also implicate social support as a factor to consider in clinical
      interventions for children exposed to war trauma.

PMID- 23978200
TI  - Diagnosing nanoelectronic components using coherent electrons.
AB  - We present the direct observation, using off-axis electron holography (EH), of
      the electric potential distribution in the vicinity of a single carbon nanotube
      electrically biased by two closely spaced contacts. When our results are combined
      with finite element modeling, we demonstrate the ability to separately observe
      the electrostatic potential drops across the metal contacts at the interface with
      the nanotube and along the length of the nanotube itself. We demonstrate that the
      uneven resistivity of different contacts can cause an asymmetric EH phase shift,
      which can readily be identified and quantified. EH thus offers a unique and
      precise approach for in-depth understanding and quick diagnosis of many similar
      nanoscale electronic devices. 

PMID- 23978201
TI  - Investigating the electronic structure of the Atox1 copper(I) transfer mechanism
      with density functional theory.
AB  - To maintain correct copper homeostasis, the body relies on ion binding
      metallochaperones, cuprophilic ligands, and proteins to move copper around as a
      complexed metal. The most common binding site for Cu(I) proteins is the CX1X2C
      motif, where X1 and X2 are nonconserved residues. Although this binding site
      motif is well established, the mechanistic and electronic details for the
      transfer of Cu(I) between two binding sites have not been fully established, in
      particular, whether the transfer is dissociative or associative or if the
      electron-rich Cu(I)-Cys interactions influence the transfer. In this work, we
      investigated the electronic structure of the Cu(I)-S interactions during the
      copper transfer between Atox1 and a metal binding domain on the ATP7A or ATP7B
      protein. Initially, three Cu(I) methylthiolate complexes, [Cu(SCH3)2](-1),
      [Cu(SCH3)3](-2), [Cu(SCH3)4](-3), were investigated with density functional
      theory (DFT) to fully elucidate the electronic structure and bonding between
      Cu(I) and thiolate species. The two-coordinate, linear species with a C-S-S-C
      dihedral angle of ~90 degrees  is the lowest energy conformation because the
      filled pi antibonding orbitals are stabilized in this geometry. The importance of
      pi-overlap is also seen with the trigonal planar, three-coordinate Cu(I) complex,
      which is similarly stabilized. A corresponding four-coordinate species could not
      be consistently optimized, so it was concluded that tetrahedral coordination was
      not likely to be stable. The transfer of Cu(I) from the Atox1 metallochaperone to
      a metal binding domain of the ATP7A or ATP7B protein was then modeled by using
      the CGGC Atox1 binding site for the donor model and the dithiotreitol ligand
      (DTT) for the acceptor model. The two- and three-coordinate intermediates
      calculated along the five-step transfer mechanism converged to near optimal Cu-S
      pi-overlap for the respective geometries, which demonstrates that the electronic
      structure in this electron-rich environment influences the intermediate's
      geometries in the transfer mechanism. 

PMID- 23978192
TI  - Severe chronic bronchitis in advanced emphysema increases mortality and
      hospitalizations.
AB  - BACKGROUND: Chronic bronchitis in COPD has been associated with an increased
      exacerbation rate, more hospitalizations, and an accelerated decline in lung
      function. The clinical characteristics of patients with advanced emphysema and
      chronic bronchitis have not been well described. METHODS: Patients randomized to
      medical therapy in the National Emphysema Treatment Trial were grouped based on
      their reports of cough and phlegm on the St. George's Respiratory
      Questionnaire(SGRQ) at baseline: chronic bronchitis(CB+) and no chronic
      bronchitis(CB-). The patients were similarly categorized into severe chronic
      bronchitis(SCB+) or no severe chronic bronchitis (SCB-) based on the above
      definition plus report of chest trouble. Kaplan-Meier survival analysis was used
      to determine the relationships between chronic bronchitis and severe chronic
      bronchitis and survival and time to hospitalization. Lung function and SGRQ
      scores over time were compared between groups. RESULTS: The CB+(N = 234; 38%) and
      CB- groups(N = 376; 62%) had similar survival (median 60.8 versus 65.7 months, p
      = 0.19) and time to hospitalization (median 26.9 versus 24.9 months, p = 0.84).
      The SCB+ group(N = 74; 12%) had worse survival (median 47.7 versus 65.7 months, p
      = 0.02) and shorter time to hospitalization (median 18.5 versus 26.7 months, p =
      0.02) than the SCB- group (N = 536; 88%). Mortality and hospitalization rates
      were not increased when chest trouble was analyzed by itself. The CB+ and CB
      groups had similar lung function and SGRQ scores over time. The SCB+ and SCB
      groups had similar lung function over time, but the SCB+ group had significantly
      worse SGRQ scores. CONCLUSIONS: Severe chronic bronchitis is associated with
      worse survival, shorter time to hospitalization, and worse health-related quality
      of life.

PMID- 23978202
TI  - Highly efficient TiO2-based microreactor for photocatalytic applications.
AB  - A photocatalytic, TiO2-based microreactor is designed and fabricated on a metal
      titanium foil. The microchannel is mechanically engraved in the substrate foil,
      and a double-layered TiO2 anatase film is immobilized on its inner walls with a
      two-step synthesis, which included anodization and a hydrothermal treatment. X
      ray diffraction (XRD) and scanning electron microscopy (SEM) confirm the presence
      of an approximately 10-MUm-thick layer of titania nanotubes and anatase
      nanoparticles. The SEM and transmission electron microscopy (TEM) of the cross
      sections show a dense interface between the titanium substrate and the TiO2
      nanotubes. An additional layer of TiO2-anatase nanoparticles on the top of the
      film provides a large, photocatalytic surface area. The metal-titanium substrate
      with a functionalized serpentine channel is sealed with UV-transparent Plexiglas,
      and four 0.8-mW UV LEDs combined with a power controller on a small printed
      circuit board are fixed over the substrate. The photocatalytic activity and the
      kinetic properties for the degradation of caffeine are provided, and the longer
      term stability of the TiO2 film is evaluated. The results show that after 6
      months of use and 3600 working cycles the microreactor still exhibits 60% of its
      initial efficiency. 

PMID- 23978214
TI  - Sets within sets: the influence of set membership on numerical estimates.
AB  - Navigating the world requires attention to number; however, sets in real-world
      contexts are rarely homogeneous or presented in isolation, thus the task of
      determining what constitutes a relevant set for enumeration can be a difficult
      one. This contextual ambiguity increases the likelihood that irrelevant sets may
      bias our ability to accurately track number. In the current study, we
      investigated whether numerical estimates are influenced by irrelevant set
      information, such as the size of other present subsets or the number of subsets
      composing the set. Adult observers were shown brief arrays of dots containing 1
      or 2 intermixed subsets, differentiated by color, and were asked to estimate the
      number of either: (1) 1 of the subsets or (2) the superset (total number of
      dots). When estimating the size of a subset, numerical estimates were greatly
      influenced by the size of the other, irrelevant subset, suggesting that the
      presence of extraneous sets may hinder accurate number judgments. Furthermore,
      when asked to judge the total number of items (the superset), observers judged
      supersets comprising 2 subsets as more numerous compared to those comprising only
      a single subset. Importantly, both trends were apparent even when observers had
      prior information about the identity of the target set, suggesting adults
      preattentively parse the world into sets, causing numerical biases that are not
      under conscious control. Potential explanations for this pattern of results,
      including simultaneous numerical contrast effects and superset summation, are
      discussed.

PMID- 23978216
TI  - Stereochemical inversion of a cyano-stabilized grignard reagent: remarkable
      effects of the ethereal solvent structure and concentration.
AB  - Chiral organometallic reagents are useful in asymmetric synthesis, and
      configurational stability of these species is critical to success. In this study
      we followed the epimerization of a chiral Grignard reagent, prepared by Mg/Br
      exchange of bromonitrile trans-2b. This compound underwent highly retentive Mg/Br
      exchange in Et2O; less retention was observed in 2-MeTHF and THF. Epimerization
      rate constants k(tc) were determined at 195 K by measuring the diastereomer ratio
      of deuteration product d1-3b as a function of the delay time before quench.
      Studies were also performed at varying concentrations of Et2O in toluene.
      Remarkable dynamic range in k(tc) was seen: relative to reaction at 0.12 M Et2O
      in toluene, epimerization was 26-, 800-, and 1300-fold faster in Et2O, 2-MeTHF,
      and THF, respectively. Thus, the identity and concentration of an ethereal
      solvent can dramatically affect configurational stability. Reaction stoichiometry
      experiments suggested that, in Et2O, the Grignard reagent derived from trans-2b
      exists as an i-PrMgCl heterodimer; the invariance of k(tc) over a 20-fold range
      in [Mg]total ruled out mandatory deaggregation (or aggregation) on the
      epimerization path. Analysis of the dependency of k(tc) on [Et2O] and temperature
      in Et2O/toluene solution at 195, 212, and 231 K indicated fast incremental
      solvation before rate-limiting ion-pair separation and provided an estimate of
      the entropic cost of capturing a solvent ligand (-13 +/- 3 eu). Calculations at
      the MP2/6-31G*(PCM)//B3LYP/6-31G* level provide support for these conclusions and
      map out a possible "ionogenic conducted tour" pathway for epimerization.

PMID- 23978217
TI  - Effectiveness and reach of a directed-population approach to improving dental
      health and reducing inequalities: a cross sectional study.
AB  - BACKGROUND: Childsmile School adopts a directed-population approach to target
      fluoride varnish applications to 20% of the primary one (P1) population in
      priority schools selected on the basis of the proportion of enrolled children
      considered to be at increased-risk of developing dental caries. The study sought
      to compare the effectiveness of four different methods for identifying
      individuals most in need when a directed-population approach is taken. METHODS:
      The 2008 Basic National Dental Inspection Programme (BNDIP) cross-sectional P1
      Scottish epidemiological survey dataset was used to model four methods and test
      three definitions of increased-risk. Effectiveness was determined by the positive
      predictive value (PPV) and explored in relation to 1-sensitivity and 1
      specificity. RESULTS: Complete data was available on 43,470 children (87% of the
      survey). At the Scotland level, at least half (50%) of the children targeted were
      at increased-risk irrespective of the method used to target or the definition of
      increased-risk. There was no one method across all definitions of increased-risk
      that maximised PPV. Instead, PPV was highest when the targeting method
      complimented the definition of increased-risk. There was a higher percentage of
      children at increased-risk who were not targeted (1-sensitivity) when caries
      experience (rather than deprivation) was used to define increased-risk,
      irrespective of the method used for targeting. Over all three definitions of
      increased-risk, there was no one method that minimised (1-sensitivity) although
      this was lowest when the method and definition of increased-risk were
      complimentary. The false positive rate (1-specificity) for all methods and all
      definitions of increased-risk was consistently low (<20%), again being lowest
      when the method and definition of increased-risk were complimentary. CONCLUSION:
      Developing a method to reach all (or even the vast majority) of individuals at
      increased-risk defined by either caries experience or deprivation is difficult
      using a directed-population approach at a group level. There is a need for a
      wider debate between politicians and public health experts to decide how best to
      reach those most at need of intervention to improve health and reduce
      inequalities.

PMID- 23978218
TI  - Structural modeling of dahlia-type single-walled carbon nanohorn aggregates by
      molecular dynamics.
AB  - The structure of dahlia-type single-walled carbon nanohorn aggregates has been
      modeled by classical molecular dynamics simulations, and the validity of the
      model has been verified by neutron diffraction. Computer-generated models
      consisted of an outer part formed from single-walled carbon nanohorns with
      diameters of 20-50 A and a length of 400 A and an inner turbostratic graphite
      like core with a diameter of 130 A. The diffracted intensity and the pair
      correlation function computed for such a constructed model are in good agreement
      with the neutron diffraction experimental data. The proposed turbostratic inner
      core explains the occurrence of the additional (002) and (004) graphitic peaks in
      the diffraction pattern of the studied sample and provides information about the
      interior structure of the dahlia-type aggregates. 

PMID- 23978219
TI  - Plasma volume expansion from the intravenous glucose tolerance test before and
      after hip replacement surgery.
AB  - BACKGROUND: Hyperosmotic glucose is injected intravenously when an intravenous
      glucose tolerance test (IVGTT) is initiated. The extent and time period of plasma
      volume expansion that occurs in response to the glucose load has not been studied
      in the perioperative setting. METHODS: Twenty-two non-diabetic patients aged
      between 57 and 76 years (mean 68) underwent an IVGTT, during which 0.3 g/kg of
      glucose 30% (1 ml/kg) was injected as a bolus over one minute, one day before and
      two days after hip replacement surgery. Twelve blood samples were collected over
      75 minutes from each patient. The turnover of both the exogenous glucose and the
      injected fluid volume was calculated by means of mass balance and volume kinetic
      analysis. RESULTS: The IVGTT raised plasma glucose by 9 mmol/L and the plasma
      volume by 8%. The extracellular fluid volume increased by 320 (SD 60) ml of which
      2/3 could be accounted for in the plasma. The half-life of the exogenous glucose
      averaged 30 minutes before surgery and 36 minutes postoperatively (P < 0.02). The
      glucose elimination governed 86% of the decay of the plasma volume expansion,
      which occurred with a half-life of 12 minutes before to 21 minutes after the
      surgery (median, P < 0.001). CONCLUSION: Hyperosmotic glucose translocated
      intracellular water to the plasma volume rather than to the entire extracellular
      fluid volume. The preferential re-distribution acts to dilute the plasma
      concentrations used to quantify insulin sensitivity and beta-cell function from
      an IVGTT. The greater-than-expected plasma dilution lasted longer after than
      before surgery.

PMID- 23978221
TI  - Local reorganization of diblock copolymer domains in directed self-assembly
      monitored by in situ high-temperature AFM.
AB  - In situ high-temperature AFM was used to locally follow dynamic processes,
      leading to directed self-assembly of copolymers in the context of graphoepitaxy.
      We focused on the effect of heating for temperatures much higher than the Tg of
      the used PS-b-PMMA polymer. We showed that such conditions favors the block
      rearrangement, leading to very regular and perfectly aligned structures in
      limited times. The use of in situ AFM allowed us to locally investigate the self
      organization process at high temperature, thus bringing new insights into self
      assembly of block copolymers by graphoepitaxy. In particular, we demonstrate that
      a slight increase of temperature between 180 and 200  degrees C allowed
      overpassing an energy barrier and considerably improves the long distance
      arrangement, even for relatively short times. 

PMID- 23978220
TI  - The prevalence of posttraumatic stress among women requesting induced abortion.
AB  - OBJECTIVES: To describe the prevalence and pattern of traumatic experiences, to
      assess the prevalence of posttraumatic stress disorder (PTSD) and posttraumatic
      stress symptoms (PTSS), to identify risk factors for PTSD and PTSS, and to
      analyse the association of PTSD and PTSS with concomitant anxiety and depressive
      symptoms in women requesting induced abortion. METHODS: A Swedish multi-centre
      study of women requesting an induced abortion. The Screen Questionnaire -
      Posttraumatic Stress Disorder was used for research diagnoses of PTSD and PTSS.
      Anxiety and depressive symptoms were evaluated by the Hospital Anxiety and
      Depression Scale (HADS). RESULTS: Of the 1514 respondents, almost half reported
      traumatic experiences. Lifetime- and point prevalence of PTSD were 7% (95%
      confidence interval [CI]: 5.8-8.5) and 4% (95% CI: 3.1-5.2), respectively. The
      prevalence of PTSS was 23% (95% CI: 21.1-25.4). Women who reported symptoms of
      anxiety or depression when requesting abortion were more likely to have ongoing
      PTSD or PTSS. Also single-living women and smokers displayed higher rates of
      ongoing PTSD. CONCLUSIONS: Although PTSD is rare among women who request an
      induced abortion, a relatively high proportion suffers from PTSS. Abortion
      seeking women with trauma experiences and existing or preexisting mental
      disorders need more consideration and alertness when counselled for termination.

PMID- 23978222
TI  - A double-blind placebo-controlled cross-over study of the vascular effects of
      midodrine in neuropathic compared with hyperadrenergic postural tachycardia
      syndrome.
AB  - POTS (postural tachycardia syndrome) is a chronic form of OI (orthostatic
      intolerance). Neuropathic POTS is characterized by decreased adrenergic
      vasoconstriction, whereas hyperadrenergic POTS exhibits increased adrenergic
      vasoconstriction. We hypothesized that midodrine, an alpha1-adrenergic receptor
      agonist, would increase CVR (calf vascular resistance), decrease C(v) (calf
      venous capacitance) and decrease orthostatic tachycardia in neuropathic POTS, but
      not alter haemodynamics in hyperadrenergic POTS. A total of 20 POTS patients (12
      neuropathic and eight hyperadrenergic), ages 12-20 years, participated in this
      randomized placebo-controlled double-blind cross-over study. Of these subjects,
      15 were female. POTS subjects received 2 weeks of treatment with midodrine or
      placebo, with increased dosing from 2.5 to 10 mg three times daily. Following a 7
      day drug-washout period, subjects received the cross-over treatment. HR (heart
      rate), MAP (mean arterial pressure), Q(calf) (calf blood flow) and CVR were
      measured supine and during 35 degrees  HUT (head-up tilt). C(v) was measured
      supine. In neuropathic POTS, midodrine decreased supine HR, Q(calf) and C(v),
      while increasing MAP and CVR compared with placebo. During HUT, in neuropathic
      POTS, midodrine decreased HR, Q(calf) and C(v), while increasing MAP and CVR. In
      hyperadrenergic POTS, placebo and midodrine both decreased upright HR and
      increased supine CVR. Placebo also increased supine C(v), compared with midodrine
      in hyperadrenergic POTS. Therefore midodrine improved postural tachycardia in
      neuropathic POTS by increasing CVR and decreasing Q(calf) and C(v), whereas these
      effects were not seen in hyperadrenergic POTS patients who experienced a placebo
      effect. This suggests that midodrine is probably an effective treatment for
      neuropathic POTS, but not for hyperadrenergic POTS.

PMID- 23978224
TI  - Ultrahigh currents in dielectric-coated carbon nanotube probes.
AB  - Carbon nanotubes used as conductive atomic force microscopy probes are expected
      to withstand extremely high currents. However, in existing prototypes,
      significant self-heating results in rapid degradation of the nanotube probe.
      Here, we investigate an alternative probe design, fabricated by dielectric
      encapsulation of multiwalled carbon nanotubes, which can support unexpectedly
      high currents with extreme stability. We show that the dielectric coating acts as
      a reservoir for Joule heat removal, and as a chemical barrier against thermal
      oxidation, greatly enhancing transport properties. In contact with Au surfaces,
      these probes can carry currents of 0.12 mA at a power of 1.5 mW and show no
      measurable change in resistance at current densities of 10(12) A/m(2) over a time
      scale of 10(3) s. Our observations are in good agreement with theoretical
      modeling and exact numerical calculations, demonstrating that the enhanced
      transport characteristics of such probes are governed by their more effective
      heat removal mechanisms. 

PMID- 23978225
TI  - Marinite Li2M(SO4)2 (M = Co, Fe, Mn) and Li1Fe(SO4)2: model compounds for super
      super-exchange magnetic interactions.
AB  - New materials initially designed for battery electrodes are often of interest for
      magnetic study, because their chemical compositions include 3d transition metals.
      We report here on the magnetic properties of marinite phases Li2M(SO4)2 (M = Fe,
      Co, Mn) and Li1Fe(SO4)2, which all order antiferromagnetically at low
      temperature. From neutron powder diffraction, we propose a model for their ground
      state magnetic structures. The magnetism of marinite Li2M(SO4)2 compounds
      unambiguously results from super-super-exchange interactions; therefore, these
      materials can be considered as a model case for which the Goodenough-Kanamori
      Anderson rules can be tested. 

PMID- 23978223
TI  - Identification of novel alpha-n-methylation of CENP-B that regulates its binding
      to the centromeric DNA.
AB  - The eukaryotic centromere is an essential chromatin region required for accurate
      segregation of sister chromatids during cell division. Centromere protein B (CENP
      B) is a highly conserved protein which can bind to the 17-bp CENP-B box on the
      centromeric DNA. In this study, we found that CENP-B could be alpha-N-methylated
      in human cells. We also showed that the level of the alpha-N-methylation was
      stimulated in cells in response to a variety of extracellular stimuli, including
      increased cell density, heat shock, and arsenite treatment, although the
      methylation level was not altered upon metaphase arrest. We identified N-terminal
      RCC1 methyltransferase (NRMT) as a major enzyme required for the CENP-B
      methylation. Additionally, we found that chromatin-bound CENP-B was primarily
      trimethylated and alpha-N-trimethylation could enhance CENP-B's binding to CENP-B
      box in cells. Our study also expands the function of protein alpha-N-methylation
      that has been known for decades and whose function remains largely unexplored. 

PMID- 23978227
TI  - Biopsychosocial outcome after uncomplicated mild traumatic brain injury.
AB  - The purpose of this study was to examine the biopsychosocial outcome from
      uncomplicated mild traumatic brain injury (MTBI) within the first 3 weeks post
      injury. Participants were 48 prospectively enrolled patients from the Emergency
      Department of Tampere University Hospital, Finland, who sustained an
      uncomplicated MTBI. At 3 weeks post injury, diffusion tensor imaging (DTI) of the
      whole brain was undertaken using a Siemens 3T scanner. Measures of fractional
      anisotropy (FA) were calculated for 16 regions of interest (ROIs) and measures of
      apparent diffusion coefficient (ADC) were calculated for 10 ROIs. Twenty-four
      healthy control participants also completed DTI of the whole brain for
      comparison. Participants were administered a brief battery of self-report (e.g.,
      postconcussion symptoms, depression, and fatigue) and neurocognitive measures
      (e.g., verbal learning and memory). There were no significant differences between
      the uncomplicated MTBI and healthy control group on any measures of learning and
      memory. Compared to the control group, the uncomplicated MTBI group reported a
      greater number of postconcussion symptoms and fatigue, but not depression. When
      considering all DTI ROIs simultaneously, the MTBI group had a significantly
      larger number of low DTI measures (FA values) compared to the healthy controls.
      MTBI patients with multifocal white matter changes did not show evidence of worse
      symptoms, cognitive impairment, or slower return to work compared to MTBI
      patients with broadly normal white matter.

PMID- 23978226
TI  - Modification of hematopoietic stem/progenitor cells with CD19-specific chimeric
      antigen receptors as a novel approach for cancer immunotherapy.
AB  - Chimeric antigen receptors (CARs) against CD19 have been shown to direct T-cells
      to specifically target B-lineage malignant cells in animal models and clinical
      trials, with efficient tumor cell lysis. However, in some cases, there has been
      insufficient persistence of effector cells, limiting clinical efficacy. We
      propose gene transfer to hematopoietic stem/progenitor cells (HSPC) as a novel
      approach to deliver the CD19-specific CAR, with potential for ensuring persistent
      production of effector cells of multiple lineages targeting B-lineage malignant
      cells. Assessments were performed using in vitro myeloid or natural killer (NK)
      cell differentiation of human HSPCs transduced with lentiviral vectors carrying
      first and second generations of CD19-specific CAR. Gene transfer did not impair
      hematopoietic differentiation and cell proliferation when transduced at 1-2
      copies/cell. CAR-bearing myeloid and NK cells specifically lysed CD19-positive
      cells, with second-generation CAR including CD28 domains being more efficient in
      NK cells. Our results provide evidence for the feasibility and efficacy of the
      modification of HSPC with CAR as a strategy for generating multiple lineages of
      effector cells for immunotherapy against B-lineage malignancies to augment graft
      versus-leukemia activity.

PMID- 23978228
TI  - Testing the influence of various conditions on the migration of epoxidised
      soybean oil from polyvinylchloride gaskets.
AB  - Epoxidised soybean oil (ESBO) is widely used as a plasticiser and stabiliser
      mainly in food contact materials on the base of polyvinylchloride (PVC),
      especially in the gaskets of jar lids. PVC gaskets containing 10-37% of ESBO were
      prepared by the baking of PVC plastisols at various process temperatures (180-240
      degrees C) in the laboratory. ESBO migration into olive oil and 3% acetic acid
      was studied at various temperatures (4 degrees C, 25 degrees C, 40 degrees C and
      60 degrees C) during a storage time up to 12 months. ESBO released into food
      simulants was transmethylated, derivatised and analysed by gas chromatography
      mass spectrometry (GC/MS). The effect of food processing, i.e. pasteurisation (80
      degrees C and 100 degrees C) and sterilisation (125 degrees C) on ESBO migration
      was also evaluated. The results were critically assessed with respect to the test
      conditions of specific migration in accordance with the current European Union
      legislation (Regulation (EU) No. 10/2011). The levels of ESBO migration found
      confirmed that the test conditions (i.e. 40 degrees C or 60 degrees C, 10 days)
      representing contact in the worst foreseeable use scenario seem to be
      insufficient for the simulation of ESBO migration during long-term storage and
      thus do not provide satisfactory objective results. 

PMID- 23978229
TI  - Patterned free-standing conductive nanofilms for ultraconformable circuits and
      smart interfaces.
AB  - A process is presented for the fabrication of patterned ultrathin free-standing
      conductive nanofilms based on an all-polymer bilayer structure composed of
      poly(3,4-ethylenedioxythiophene)/poly(styrene sulfonate) and poly(lactic acid)
      (PEDOT:PSS/PLA). Based on the strategy recently introduced by our group for
      producing large area free-standing nanofilms of conductive polymers with
      ultrahigh conformability, here an inkjet subtractive patterning technique was
      used, with localized overoxidation of PEDOT:PSS that caused the local
      irreversible loss of electrical conductivity. Different pattern geometries (e.g.,
      interdigitated electrodes with various spacing, etc.) were tested for validating
      the proposed process. The fabrication of individually addressable microelectrodes
      and simple circuits on nanofilm having thickness ~250 nm has been demonstrated.
      Using this strategy, mechanically robust, conformable ultrathin polymer films
      could be produced that can be released in water as free-standing nanofilms and/or
      collected on surfaces with arbitrary shapes, topography and compliance, including
      human skin. The patterned bilayer nanofilms were characterized as regards their
      morphology, thickness, topography, conductivity, and electrochemical behavior. In
      addition, the electrochemical switching of surface properties has been evaluated
      by means of contact angle measurements. These novel conductive materials can find
      use as ultrathin, conformable electronic devices and in many bioelectrical
      applications. Moreover, by exploiting the electrochemical properties of
      conducting polymers, they can act as responsive smart biointerfaces and in the
      field of conformable bioelectronics, for example, as electrodes on tissues or
      smart conductive substrates for cell culturing and stimulation. 

PMID- 23978231
TI  - Mood and anxiety disorders in chimpanzees (pan troglodytes): A response to Rosati
      et al. (2012).
AB  - Assessing the psychological health of nonhuman primates living in captivity is
      essential, since many experiments and behavioral observations involve captive
      animals. This area is a research priority because it has ethical consequences, in
      addition to its applications for understanding human and nonhuman primate
      behavior. In 2011, we published our international study's findings that
      chimpanzees with prior histories of experimentation, orphanage, illegal seizure,
      or violent human conflict were more likely to display signs of mood and anxiety
      disorders, compared with chimpanzees living in the wild. Here, in response to
      Rosati and colleagues (2012), we address methodological challenges relevant to
      the application of human diagnostic psychiatric criteria to nonverbal animals. We
      also review the importance of understanding psychopathology using a holistic
      approach based on evolutionary psychiatry and suggest a way forward, integrating
      ethological, veterinary, and human psychiatric approaches.

PMID- 23978233
TI  - Seed-mediated synthesis of core/shell FePtM/FePt (M = Pd, Au) nanowires and their
      electrocatalysis for oxygen reduction reaction.
AB  - We report a new seed-mediated growth of FePt over 2.5 nm wide FePtM (M = Pd, Au)
      nanowires (NWs) into core/shell FePtM/FePt NWs with controlled FePt shell
      thickness from 0.3 to 1.3 nm. These FePtM/FePt NWs show shell thickness and core
      composition-dependent electrocatalytic activity for oxygen reduction reaction
      (ORR) in 0.1 M HClO4. These core/shell FePtM/FePt NWs are generally more active
      and durable than the corresponding alloy NWs. Among FePtM/FePt NWs, FePt NWs,
      FePtPd NWs, and commercial Pt studied, the FePtPd/FePt NWs (0.8 nm shell) show
      the specific activity of 3.47 mA.cm(-2) and the mass activity of 1.68 A/mg Pt at
      0.5 V (vs. Ag/AgCl), superior to all other NWs (less than 1.59 mA/cm(2) and 0.82
      A/mg Pt for FePtAu/FePt and FePt) as well as the commercial Pt (0.24 mA/cm(2) and
      0.141 A/mg Pt). The FePtM/FePt (0.8 nm shell) NWs are also stable in the ORR
      condition and show no activity decrease after 5000 potential sweeps between 0.4
      and 0.8 V (vs Ag/AgCl). They are the most efficient nanocatalyst ever reported
      for ORR. 

PMID- 23978234
TI  - On the transfer of prior tests or study events to subsequent study.
AB  - Tests, as learning events, are often more effective than are additional study
      opportunities, especially when recall is tested after a long retention interval.
      To what degree, though, do prior test or study events support subsequent study
      activities? We set out to test an implication of Bjork and Bjork's (1992) new
      theory of disuse-that, under some circumstances, prior study may facilitate
      subsequent study more than does prior testing. Participants learned English
      Swahili translations and then underwent a practice phase during which some items
      were tested (without feedback) and other items were restudied. Although tested
      items were better recalled after a 1-week delay than were restudied items, this
      benefit did not persist after participants had the opportunity to study the items
      again via feedback. In fact, after this additional study opportunity, items that
      had been restudied earlier were better recalled than were items that had been
      tested earlier. These results suggest that measuring the memorial consequences of
      testing requires more than a single test of retention and, theoretically, a
      consideration of the differing status of initially recallable and nonrecallable
      items.

PMID- 23978235
TI  - Dual-retrieval models and neurocognitive impairment.
AB  - Advances in dual-retrieval models of recall make it possible to use clinical data
      to test theoretical hypotheses about mild cognitive impairment (MCI) and
      Alzheimer's dementia (AD), the most common forms of neurocognitive impairment.
      Hypotheses about the nature of the episodic memory declines in these diseases,
      about decline versus sparing of specific processes, and about which individuals
      will become impaired over time can all be rigorously tested. Basic theoretical
      principles, such as whether recollection and reconstruction are distinct
      retrieval processes, can also be evaluated. In 3 studies, measurements of
      recollective retrieval, reconstructive retrieval, and familiarity judgment were
      extracted from standard clinical instruments, for healthy subjects and for
      subjects with MCI and AD diagnoses. Differences in reconstructive retrieval
      consistently distinguished MCI and AD, in nationally representative subject
      samples as well as in highly educated samples, and recollective retrieval also
      distinguished them in highly educated samples. Dual-retrieval processes were
      accurate predictors of future conversion to MCI and AD over periods of 1.5-6
      years and were better predictors than the best genetic marker of these conditions
      (the epsilon4 allele of the APOE genotype). The standard recollection-deficit
      account of memory declines in MCI and AD was not supported, but the data were
      consistent with an alternative account that stresses the increasing importance of
      reconstruction deficits as older adults convert to these diseases.

PMID- 23978237
TI  - Influence of headgroup on the aggregation and interactional behavior of twin
      tailed cationic surfactants with pluronics.
AB  - The surface tension measurements have been employed to characterize the micellar
      and interfacial behavior of pure and mixed systems of twin-tailed cationic
      surfactants: dimethylene bis(decyldimethylammonium bromide) (10-2-10),
      didecydimethylammonium bromide (DDAB), and 1,3-didecyl-2-methylimidazolium
      chloride (DDIC) with pluronics P84 and F108 in the aqueous solution. The
      interactions of each surfactant with both pluronics are found to be nonideal and
      synergistic except for the mixed system of 10-2-10 + F108, for which interactions
      are antagonistic and every interaction has been studied on the basis of headgroup
      disparity. Dynamic light scattering (DLS), zeta (zeta) potential, and small angle
      neutron scattering (SANS) measurements have been used to determine the influence
      of the mixing ratio on the morphology of the various mixed aggregates that are
      formed. Pure DDAB is found to form unilamellar vesicles whereas pure 10-2-10 and
      DDIC form prolate ellipsoidal micelles. The unilamellar vesicles of DDAB are
      destructed to yield spherical mixed micelles on addition of pluronics via
      expansion or contraction of vesicles. However, the pure pluronics and their mixed
      systems with 10-2-10 and DDIC form charged spherical micelles, and charge is
      confirmed by thenfractional charge and zeta values. The zeta values of pure
      surfactants are found to decrease on addition of pluronics, indicating a decrease
      in surface charge on inclusion of pluronics. 

PMID- 23978236
TI  - Disparities in child mortality trends in two new states of India.
AB  - BACKGROUND: India has the world's highest total number of under-five deaths of
      any nation. While progress towards Millennium Development Goal 4 has been
      documented at the state level, little information is available for greater
      disaggregation of child health markers within states. In 2000, new states were
      created within the country as a partial response to political pressures. State
      level information on child health trends in the new states of Chhattisgarh and
      Jharkhand is scarce. To fill this gap, this article examines under-five and
      neonatal mortality across various equity markers within these two new states, pre
      and post-split. METHODS: Both direct and indirect estimation using pooled data
      from five available sources were undertaken. Inter-population disparities were
      evaluated by mortality data stratification of rural-urban location, ethnicity,
      wealth and districts. RESULTS: Both states experienced an overall reduction in
      under-five and neonatal mortality, however, this has stagnated post-2001 and
      various disparities persist. In cases where disparities have declined, such as
      between urban-rural populations and low- and high-income groups, this has been
      driven by modest declines within the disadvantaged groups (i.e. low-income rural
      households) and stagnation or worsening of outcomes within the advantaged groups.
      Indeed, rising trends in mortality are most prevalent in urban middle-income
      households. CONCLUSIONS: The results suggest that rural health improvements may
      have come at the expense of urban areas, where poor performance may be attributed
      to factors such as lack of access to quality private health facilities. In
      addition, the disparities may in part be associated with geographical access,
      traditional practices and district-level health resource allocation.

PMID- 23978238
TI  - Simultaneous determination of protein-free and total positron emission tomography
      radioligand concentrations in plasma using high-performance frontal analysis
      followed by mixed micellar liquid chromatography: application to [11C]PBR28 in
      human plasma.
AB  - A two-dimensional liquid chromatographic (LC) system was developed for the
      determination of protein-free and total (free + bound forms) positron emission
      tomography (PET) radioligand concentrations in plasma by direct plasma injection.
      The unbound PET radioligand was first analyzed by high-performance frontal
      analysis using a short gel-filtration column and phosphate buffered saline
      solution as the mobile phase. All the collected effluent from the gel-filtration
      column was then transferred to the second dimension consisting of a monolithic C
      18 column and mixed (anionic and nonionic surfactants) micellar eluent for
      determination of the total PET radioligand concentration. The simultaneous
      analysis of protein binding and radiometabolism of [(11)C]PBR28 was completed
      within 11 min without any pretreatment of plasma and employing a single
      analytical system. This system allowed highly sensitive analysis of total
      [(11)C]PBR28 with a limit of detection (LOD) of 1.6 becquerel (Bq). The LOD for
      the determination of unbound [(11)C]PBR28 was 21 Bq. Finally, simultaneous
      measurements of protein binding and radiometabolism of [(11)C]PBR28 in human
      plasma were achieved for up to 50 min after radioligand administration. 

PMID- 23978239
TI  - Oscillations in the permanganate oxidation of glycine in a stirred flow reactor.
AB  - Oscillatory behavior is reported in the permanganate oxidation of glycine in the
      presence of Na2HPO4 in a stirred flow reactor. In near-neutral solutions, long
      period sustained oscillations were recorded in the potential of a Pt electrode
      and in the light absorbance measured at lambda = 418 and 545 nm, characteristic
      wavelengths for following the evolution of the intermediate [Mn(IV)] and reagent
      [MnO4(-) ] during the course of the reaction. No evidence of bistability was
      found. The chemical and physical backgrounds of the oscillatory phenomenon are
      discussed. In the oscillatory cycle, the positive feedback is attributed to the
      autocatalytic formation of a soluble Mn(IV) species, whereas the negative
      feedback arises from its removal from the solution in the form of solid MnO2. A
      simple model is suggested that qualitatively simulates the experimental
      observations in batch runs and the dynamics that appears in the flow system. 

PMID- 23978240
TI  - Expanding contraceptive choice in the developing world: lessons from the Lao
      People's Democratic Republic and the Republic of Zambia.
AB  - BACKGROUND AND OBJECTIVES: Women need different forms of contraception over their
      lifetime. In the developed world, they have access to some 20 different methods.
      In developing countries, only a few options are available. This paper focuses on
      four under-used methods: intrauterine devices, implants, emergency contraception
      and female condoms. It examines reasons for their low uptake, strategies used for
      their adoption, and challenges in sustaining these efforts, in two countries:
      Laos and Zambia. METHODS: In-country documentation and reports from international
      partners were reviewed; questionnaires were sent and interviews carried out with
      ministry officials, senior providers, and local representatives of international
      organisations and international non-governmental organisations. RESULTS: In Laos,
      the family planning programme is relatively young; its challenges include
      ensuring the sustainability of services and supplies, improving the quality of
      IEC to dispel misconceptions surrounding contraception, and developing novel
      distribution systems to reach rural populations. Zambia has a much older
      programme, which lost ground in the face of competing health priorities. Its
      challenges include strengthening the supply chain management, coordinating the
      multiple groups of providers and ensuring the sustainability of services in rural
      areas. CONCLUSIONS: The contrast offered by Laos and Zambia illustrates the
      importance of regular evaluation to identify priority areas for improving
      contraceptive delivery.

PMID- 23978241
TI  - Synthesis of isomeric isothiazolo[4',3':4,5]- and
      isothiazolo[4',5':4,5]thieno[3,2-b]pyrano[2,3-d]pyridines by combination of
      domino reactions.
AB  - Isothiazolothienopyridines have been prepared by a domino reaction (the SN2
      reaction -> the Thorpe-Ziegler reaction -> the Thorpe-Guareschi reaction type)
      from disodium 4-cyanoisothiazole-3,5-dithiolate. By changing the order of
      addition of the alkylation reagents in the reaction with disodium 4
      cyanoisothiazole-3,5-dithiolate both possible isomers of the
      isothiazolothienopyridines are synthesized. These isomers were further used in
      three-component domino reaction (the Knoevenagel reaction -> the Michael reaction
      -> the hetero-Thorpe-Ziegler reaction type) to obtain wide range of isomeric
      isothiazolothienopyranopyridines. 

PMID- 23978242
TI  - A safe and convenient pseudovirus-based inhibition assay to detect neutralizing
      antibodies and screen for viral entry inhibitors against the novel human
      coronavirus MERS-CoV.
AB  - BACKGROUND: Evidence points to the emergence of a novel human coronavirus, Middle
      East respiratory syndrome coronavirus (MERS-CoV), which causes a severe acute
      respiratory syndrome (SARS)-like disease. In response, the development of
      effective vaccines and therapeutics remains a clinical priority. To accomplish
      this, it is necessary to evaluate neutralizing antibodies and screen for MERS-CoV
      entry inhibitors. METHODS: In this study, we produced a pseudovirus bearing the
      full-length spike (S) protein of MERS-CoV in the Env-defective, luciferase
      expressing HIV-1 backbone. We then established a pseudovirus-based inhibition
      assay to detect neutralizing antibodies and anti-MERS-CoV entry inhibitors.
      RESULTS: Our results demonstrated that the generated MERS-CoV pseudovirus allows
      for single-cycle infection of a variety of cells expressing dipeptidyl peptidase
      4 (DPP4), the confirmed receptor for MERS-CoV. Consistent with the results from a
      live MERS-CoV-based inhibition assay, the antisera of mice vaccinated with a
      recombinant protein containing receptor-binding domain (RBD, residues 377-662) of
      MERS-CoV S fused with Fc of human IgG exhibited neutralizing antibody response
      against infection of MERS-CoV pseudovirus. Furthermore, one small molecule HIV
      entry inhibitor targeting gp41 (ADS-J1) and the 3-hydroxyphthalic anhydride
      modified human serum albumin (HP-HSA) could significantly inhibit MERS-CoV
      pseudovirus infection. CONCLUSION: Taken together, the established MERS-CoV
      inhibition assay is a safe and convenient pseudovirus-based alternative to BSL-3
      live-virus restrictions and can be used to rapidly screen MERS-CoV entry
      inhibitors, as well as evaluate vaccine-induced neutralizing antibodies against
      the highly pathogenic MERS-CoV.

PMID- 23978244
TI  - Organic Li4C8H2O6 nanosheets for lithium-ion batteries.
AB  - Organic tetralithium salts of 2,5-dihydroxyterephthalic acid (Li4C8H2O6) with the
      morphologies of bulk, nanoparticles, and nanosheets have been investigated as the
      active materials of either positive or negative electrode of rechargeable lithium
      ion batteries. It is demonstrated that, in the electrolyte of LiPF6 dissolved in
      ethylene carbonate (EC) and dimethyl carbonate (DMC), reversible two-Li-ion
      electrochemical reactions are taking place with redox Li4C8H2O6/Li2C8H2O6 at ~2.6
      V for a positive electrode and Li4C8H2O6/Li6C8H2O6 at ~0.8 V for a negative
      electrode, respectively. In the observed system, the electrochemical performance
      of high to low order is nanosheets > nanoparticles > bulk. Remarkably, Li4C8H2O6
      nanosheets show the discharge capacities of 223 and 145 mAh g(-1) at 0.1 and 5 C
      rates, respectively. A capacity retention of 95% is sustained after 50 cycles at
      0.1 C rate charge/discharge and room temperature. Moreover, charging the
      symmetrical cells with Li4C8H2O6 nanosheets as the initial active materials of
      both positive and negative electrodes produces all-organic LIBs with an average
      operation voltage of 1.8 V and an energy density of about 130 Wh kg(-1),
      enlightening the design and application of organic Li-reservoir compounds with
      nanostructures for all organic LIBs.

PMID- 23978243
TI  - Regulation of pre-fusion events: recruitment of M-cadherin to microrafts
      organized at fusion-competent sites of myogenic cells.
AB  - BACKGROUND: Previous research indicates that the membrane ruffles and leading
      edge of lamellipodia of myogenic cells contain presumptive fusion sites. A
      micrometer-sized lipid raft (microraft) is organized at the presumptive fusion
      site of mouse myogenic cells in a cell-contact independent way and serves as a
      platform tethering adhesion proteins that are relevant to cell fusion. However,
      the mechanisms underlying recruitment of adhesion proteins to lipid rafts and
      microraft organization remain unknown. RESULTS: Here we show that small G-protein
      Rac1 was required for microraft organization and subsequent cell fusion. However,
      Rac1 activity was unnecessary for recruitment of M-cadherin to lipid rafts. We
      found that p120 catenin (p120) binds to M-cadherin exclusively in lipid rafts of
      differentiating myogenic cells. The Src kinase inhibitor SU6656 prevented p120
      binding to M-cadherin and their recruitment to lipid rafts, then suppressed
      microraft organization, membrane ruffling, and myogenic cell fusion. Suppression
      of membrane ruffling in SU6656-treated cells was partially restored by
      pretreatment with the protein tyrosine phosphatase inhibitor vanadate. The
      present analyses using an antibody to tyrosine phosphorylated p120 suggest that
      Src family kinases play a role in binding of p120 to M-cadherin and the
      recruitment of M-cadherin to lipid rafts through phosphorylation of putative
      substrates other than p120. CONCLUSIONS: The present study showed that the
      procedure establishing fusion-competent sites consists of two sequential events:
      recruitment of adhesion complexes to lipid rafts and organization of microrafts.
      The recruitment of M-cadherin to lipid rafts depended on interaction with p120
      catenin, whereas the organization of microrafts was controlled by a small G
      protein, Rac1.

PMID- 23978245
TI  - SMFM adopts GRADE (Grading of Recommendations Assessment, Development, and
      Evaluation) for clinical guidelines.

PMID- 23978246
TI  - Fetal blood sampling.
AB  - OBJECTIVE: We sought to review indications, technical aspects, risks, and
      recommendations for fetal blood sampling (FBS). METHODS: A systematic review was
      performed using MEDLINE, PubMed, EMBASE, and Cochrane Library using the terms
      "fetal blood sampling," "percutaneous umbilical blood sampling," and
      "cordocentesis." The search was restricted to English-language articles published
      from 1966 through July 2012. Priority was given to articles reporting original
      research, in particular randomized controlled trials, although review articles
      and commentaries also were consulted. Abstracts of research presented at symposia
      and scientific conferences were not considered adequate for inclusion in this
      document. Evidence reports and guidelines published by organizations or
      institutions such as the National Institutes of Health, Agency for Health
      Research and Quality, American Congress of Obstetricians and Gynecologists, and
      Society for Maternal-Fetal Medicine were also reviewed, and additional studies
      were located by reviewing bibliographies of identified articles. Grade (Grading
      of Recommendations Assessment, Development, and Evaluation) methodology was
      employed for defining strength of recommendations and rating quality of evidence.
      Consistent with US Preventive Task Force guidelines, references were evaluated
      for quality based on the highest level of evidence. RESULTS AND RECOMMENDATIONS:
      Ultrasound-guided FBS is the only procedure that provides direct access to the
      fetal circulation. When invasive testing is planned for suspected severe fetal
      anemia or thrombocytopenia, we recommend FBS as the procedure of choice, with
      availability of immediate transfusion if confirmed. We recommend against the use
      of FBS for indications in which other less invasive, and therefore lower risk,
      alternatives are available. The overall success rate of FBS is high, and blood
      samples can be obtained in >98% of patients. We suggest that counseling for FBS
      include discussion about the potential risk of FBS that may include, but may not
      be limited to: bleeding from puncture site (20-30%); fetal bradycardia (5-10%);
      pregnancy loss (>=1.3%, depending on indication, gestational age, and placental
      penetration); and vertical transmission of hepatitis or human immunodeficiency
      virus. We recommend that FBS be performed by experienced operators at centers
      with expertise in invasive fetal procedures when feasible.

PMID- 23978248
TI  - Impact of thyroid hormone administration on fluid requirements and hepatic injury
      markers in hemorrhagic shock due to liver trauma.
AB  - INTRODUCTION: The aim of the present study was to evaluate the effect of
      triiodothyronine (T3) administration in a porcine model of hemorrhagic shock due
      to liver surgery, in terms of hemodynamic stability, acid-base status, and
      hepatic injury markers. MATERIALS AND METHODS: Hemorrhagic shock was induced in
      swine by left lobe liver resection and allowed bleeding to a mean arterial
      pressure of 35-40 mmHg for 40 min. Animals were randomly assigned into a sham
      group (n = 5), a fluid-resuscitated group (n = 7), and a fluid plus T3
      resuscitated group (n = 7). T3 was given by continuous intravenous infusion from
      the beginning of the experiment. After the 40 min of shock animals were
      resuscitated with the aim of restoring mean arterial pressure (+/-10% from
      baseline). Resuscitation lasted for 1 hr and then swine were followed for another
      460 min (total 6 hr). Blood loss, hamodynamic parameters, fluids administered,
      acid-base status, and liver enzymes were measured. RESULTS: Blood loss was
      similar in both groups. Animals treated with T3 required less fluids than swine
      resuscitated with crystalloids and colloids only (N/S 0.9%: 1071 +/- 189 ml vs.
      2429 +/- 535 ml, Voluven 6%: 550 +/- 96 ml vs. 1000 +/- 289 ml, p < .05), plus
      they were less acidotic at the end of the observing period (7.38 +/- 0.08 vs.
      7.26 +/- 0.12, p < .05). Tachycardia was not associated with T3 administration.
      Hepatic enzymes did not exhibit differences between groups. CONCLUSION: Our study
      demonstrates the beneficial impact of T3 administration during controlled
      hemorrhagic shock and resuscitation. Animals resuscitated with T3 necessitate
      less amounts of fluids to maintain hemodynamic stability and acid-base status.
      Moreover, T3 administration does not seem to aggravate blood loss or harm the
      hepatic tissue.

PMID- 23978247
TI  - Two-photon oxygen sensing with quantum dot-porphyrin conjugates.
AB  - Supramolecular assemblies of a quantum dot (QD) associated to palladium(II)
      porphyrins have been developed to detect oxygen (pO2) in organic solvents.
      Palladium porphyrins are sensitive in the 0-160 Torr range, making them ideal
      phosphors for in vivo biological oxygen quantification. Porphyrins with meso
      pyridyl substituents bind to the surface of the QD to produce self-assembled
      nanosensors. Appreciable overlap between QD emission and porphyrin absorption
      features results in efficient Forster resonance energy transfer (FRET) for signal
      transduction in these sensors. The QD serves as a photon antenna, enhancing
      porphyrin emission under both one- and two-photon excitation, demonstrating that
      QD-palladium porphyrin conjugates may be used for oxygen sensing over
      physiological oxygen ranges. 

PMID- 23978249
TI  - Chronic postoperative Mycobacterium gordonae endophthalmitis in a patient with
      phakic intraocular lens.
AB  - METHODS: Case description of a 34 year old woman with chronic granulomatous
      anterior uveitis following implantation of a phakic anterior chamber intraocular
      lens (IOL). Aqueous humor was processed for bacterial, fungal culture, and PCR
      analysis. RESULTS: PCR for 16S ribosomal RNA universal primers was positive and
      Southern-blot for Propionibacterium spp was negative. Panfungal PCR was negative.
      Growth of a pigmented yellow colony was detected on Lowenstein-Jensen medium. The
      isolate was subsequently identified as Mycobacterium gordonae. The patient was
      treated for atypical mycobacteria as well as an intracameral injection of
      moxifloxacin, with resolution of inflammation and improvement in visual acuity.
      CONCLUSIONS: This is the first reported case of Mycobacterium gordonae chronic
      postoperative endophthalmitis, and of chronic endophthalmitis following phakic
      IOL surgery. PCR and cultures were invaluable in making the diagnosis.

PMID- 23978250
TI  - Improving pore filling of gel electrolyte and charge transport in photoanode for
      high-efficiency quasi-solid-state dye-sensitized solar cells.
AB  - We demonstrate the enhancement of pore-filling and wettability of gel electrolyte
      in quasi-solid-state dye-sensitized solar cells (DSSCs) by developing a
      kinetically driven electrolyte infiltration approach, in which the air purging
      provides the driving force. This method renders fast electrolyte diffusion
      throughout the three-dimensional TiO2 nanoparticle network, promising for large
      area device fabrication. In addition, for the first time we incorporate
      multiwalled carbon nanotubes into the anode of quasi-solid-state DSSCs to improve
      the charge transfer efficiency and fill factor. These advancements finally
      generate an efficiency exceeding 7.0%, much higher than the device efficiency of
      5.5% fabricated by the conventional method. 

PMID- 23978251
TI  - Controlled growth of atomically thin In2Se3 flakes by van der Waals epitaxy.
AB  - The controlled production of high-quality atomically thin III-VI semiconductors
      poses a challenge for practical applications in electronics, optoelectronics, and
      energy science. Here, we exploit a controlled synthesis of single- and few-layer
      In2Se3 flakes on different substrates, such as graphene and mica, by van der
      Waals epitaxy. The thickness, orientation, nucleation site, and crystal phase of
      In2Se3 flakes were well-controlled by tuning the growth condition. The obtained
      In2Se3 flakes exhibit either semiconducting or metallic behavior depending on the
      crystal structures. Meanwhile, field-effect transistors based on the
      semiconducting In2Se3 flakes showed an efficient photoresponse. The controlled
      growth of atomically thin In2Se3 flakes with diverse conductivity and efficient
      photoresponsivity could lead to new applications in photodetectors and phase
      change memory devices. 

PMID- 23978252
TI  - Diagnostic performances of various gray-scale, color Doppler, and contrast
      enhanced ultrasonography findings in predicting malignant thyroid nodules.
AB  - BACKGROUND: Ultrasonography is the most frequently used clinical tool for the
      identification, assessment, and follow-up of thyroid nodules. The purpose of this
      research was to evaluate the value of diagnostic ultrasonography indicators, to
      obtain rankings of the most valuable indicators in the differential diagnosis of
      thyroid nodules, and to analyze the optimal diagnostic points and clinical
      values. METHODS: One hundred forty-four patients with 172 thyroid nodules
      underwent preoperative ultrasonography examinations, including gray-scale
      ultrasonography (GSUS), color Doppler ultrasonography (CDUS), and contrast
      enhanced ultrasonography (CEUS). Fourteen indicators of thyroid nodules on GSUS,
      CDUS, and CEUS were selected to evaluate all thyroid nodules. The differences
      between the benign and malignant thyroid nodules in all indicators were analyzed
      by the chi-squared test; the diagnostic ultrasonography values were obtained by
      logistic regression; and the optimal diagnostic points were explored by receiver
      operating characteristic curve analysis. RESULTS: Of the 172 thyroid nodules that
      were surgically removed, 78 were benign and 94 were malignant. Ten indicators of
      GSUS and CEUS showed significant differences between the benign and malignant
      nodules (p<0.05), whereas four CDUS indicators had no value. The rankings of the
      valuable indicators were obtained according to their odds ratios (ORs). The top
      four indicators were ring enhancement and homogeneity of enhancement on CEUS, and
      microcalcification and halo on GSUS. These indicators were the most valuable,
      with ORs of greater than 20 in the differential diagnosis of benign and malignant
      thyroid nodules. The other six indicators-the relative arrival time of the nodule
      on CEUS, interior echogenicity on GSUS, peak interior echogenicity on CEUS, shape
      on GSUS, peak peripheral echogenicity on CEUS, and orientation on GSUS-were also
      valuable, with ORs less than 20. The areas under the receiver operating
      characteristic curves for GSUS, CEUS, and the combination of GSUS and CEUS in the
      diagnosis of thyroid nodules were 0.936, 0.910, and 0.966, respectively. Five
      positive features of the 10 valuable indicators on GSUS and CEUS defined the cut
      off for the diagnosis of malignant thyroid nodules, with a sensitivity of 89.4%
      (84/94), specificity of 93.6% (73/78), and accuracy of 91.3% (157/172).
      CONCLUSIONS: The ring enhancement and homogeneity of enhancement of thyroid
      nodules on CEUS and the microcalcification and halo on GSUS were the four most
      valuable indicators in the differential diagnosis of thyroid nodules. Conjoint
      analysis of specific features of thyroid nodules on GSUS and CEUS could enhance
      the diagnostic value of thyroid nodules.

PMID- 23978253
TI  - Mortality among children and youth in high-percentage First Nations identity
      areas, 2000-2002 and 2005-2007.
AB  - INTRODUCTION: Many First Nations children live in communities that face diverse
      social and health challenges compared with their non-Aboriginal peers, including
      some of the most socio-economically challenging situations in Canada. These
      differences can be seen in broad indicators of the social determinants of health.
      Studies of mortality in Aboriginal populations across Canada are often restricted
      by the lack of Aboriginal identifiers on national death records. While some
      studies have utilised a record-linkage approach, this is often not possible for
      the entire country or for recent data. Some researchers have adopted a geographic
      approach and examined mortality and morbidity in areas that have a high
      percentage of Aboriginal identity residents, and have uniformly reported elevated
      rates of mortality and morbidity compared with other areas. The purpose of this
      article was to examine child and youth mortality (aged 1 to 19 years) in areas
      where a high percentage of the population identified as First Nations in
      comparison with areas where there is a low percentage of Aboriginal identity
      residents. METHODS: Using a geographic threshold table approach, areas with a
      high percentage of Aboriginal identity peoples were classified as either First
      Nations, Metis, or Inuit communities based on the predominant identity group. The
      upper one-third of the total Aboriginal population distribution was used as a cut
      off for high percentage First Nations areas, where 97.7% of the population aged 1
      19 were of First Nations identity in 2006 (<i>N</i>=140 779). Mortality rates
      were then calculated for high-percentage First Nations identity areas and
      compared with low-percentage Aboriginal identity areas, excluding high-percentage
      Metis or Inuit identity areas. Deaths were aggregated for the 3 years surrounding
      the 2001 and 2006 census periods, and a total of 473 deaths were recorded for
      2000-2002 and 493 deaths for 2005-2007. Analysis was facilitated via the
      correspondence of six-digit residential postal codes on vital statistics records
      to census geographical areas using automated geo-coding software (Statistics
      Canada; PCCF+). RESULTS: Age-standardized mortality rates for children and youth
      in high-percentage First Nations identity areas were significantly higher than in
      low-percentage Aboriginal identity areas. The rate ratio for all-cause mortality
      for boys was 3.2 (CI: 2.9-3.6) for 2005-2007 and 3.6 (CI: 3.2-4.2) for girls.
      Mortality rates for injuries had the largest difference, with rate ratios of 4.7
      (CI: 4.0-5.5) and 5.3 (CI:4.5-6.3) for boys in 2000-2002 and 2005-2007 and 5.5
      (CI: 4.4-6.8) and 8.3 (CI: 6.8-10.1) for girls in the same period. CONCLUSION: A
      strength of this study is that it is the first to use national-level vital
      statistics registration data across two time periods to report mortality by cause
      for children and youth living in high-percentage First Nations areas. Vital
      events were geographically coded to high-percentage First Nations identity areas
      and compared with low-percentage Aboriginal identity areas at the Dissemination
      Areas level. This area-based methodology allows for mortality to be calculated
      for children and youth by sex and by detailed cause of death for multiple time
      periods. The results provide key evidence for the persistent differences in the
      causes of death for children and youth living in high-percentage First Nations
      identity areas.

PMID- 23978255
TI  - pi-Stacking, C-H/pi, and halogen bonding interactions in bromobenzene and mixed
      bromobenzene-benzene clusters.
AB  - Noncovalent interactions play an important role in many chemical and biochemical
      processes. Building upon our recent study of the homoclusters of chlorobenzene,
      where pi-pi stacking and CH/pi interactions were identified as the most important
      binding motifs, in this work we present a study of bromobenzene (PhBr) and mixed
      bromobenzene-benzene clusters. Electronic spectra in the region of the PhBr
      monomer S0-S1 (pipi*) transition were obtained using resonant two-photon
      ionization (R2PI) methods combined with time-of-flight mass analysis. As
      previously found for related systems, the PhBr cluster spectra show a broad
      feature whose center is red-shifted from the monomer absorption, and electronic
      structure calculations indicate the presence of multiple isomers and Franck
      Condon activity in low-frequency intermolecular modes. Calculations at the M06
      2X/aug-cc-pVDZ level find in total eight minimum energy structures for the PhBr
      dimer: four pi-stacked structures differing in the relative orientation of the Br
      atoms (denoted D1-D4), one T-shaped structure (D5), and three halogen bonded
      structures (D6-D8). The calculated binding energies of these complexes, corrected
      for basis set superposition error (BSSE) and zero-point energy (ZPE), are in the
      range of -6 to -24 kJ/mol. Time-dependent density functional theory (TDDFT)
      calculations predict that these isomers absorb over a range that is roughly
      consistent with the breadth of the experimental spectrum. To examine the
      influence of dipole-dipole interaction, R2PI spectra were also obtained for the
      mixed PhBr...benzene dimer, where the spectral congestion is reduced and clear
      vibrational structure is observed. This structure is well-simulated by Franck
      Condon calculations that incorporate the lowest frequency intermolecular modes.
      Calculations find four minimum energy structures for the mixed dimer and predict
      that the binding energy of the global minimum is reduced by ~30% relative to the
      global minimum PhBr dimer structure.

PMID- 23978254
TI  - Prognostic value of coronary flow reserve assessed by transthoracic Doppler
      echocardiography on long-term outcome in asymptomatic patients with type 2
      diabetes without overt coronary artery disease.
AB  - BACKGROUND: Cardiovascular risk stratification of asymptomatic diabetic patients
      is important and remains a difficult clinical problem. Our aim was to test the
      hypothesis that coronary flow reserve (CFR) assessed by noninvasive transthoracic
      Doppler echocardiography predicts prognosis in those patients. METHODS: From
      February 2002 to January 2005, we evaluated 135 consecutive asymptomatic patients
      (74 male; mean age, 63 +/- 9 years) with type 2 diabetes without a history of
      coronary artery disease. Adenosine triphosphate (0.14 mg/kg/min) stress Doppler
      echocardiography was performed to evaluate CFR of the left anterior descending
      artery. Patients with a CFR < 2.0 were also excluded based on the suspicion of
      significant coronary artery stenosis in the left anterior descending artery.
      RESULTS: There were 111 patients (60 male; mean age, 64 +/- 9 years) enrolled.
      During a median follow-up of 79 months, 20 events (5 deaths, 7 acute coronary
      syndromes, 8 coronary revascularizations) occurred. The optimal cut-off value of
      CFR to predict events was 2.5 (area under the receiver-operating characteristic
      curve = 0.65). Multivariate analysis showed that the independent prognostic
      indicators were male gender (p < 0.05) and a CFR < 2.5 (p < 0.01). Kaplan-Mayer
      analysis revealed that the event rate was significantly higher (log-lank, p <
      0.01) in patients with CFR < 2.5 than in those with CFR >= 2.5. CONCLUSIONS: CFR
      obtained by transthoracic Doppler echocardiography provides independent
      prognostic information in asymptomatic patients with type 2 diabetes without
      overt coronary artery disease. Patients with CFR < 2.5 had a worse long-term
      outcome.

PMID- 23978256
TI  - Enhancing on-surface mismatch discrimination capability of PNA probes by AuNP
      modification of gold(111) surface.
AB  - Unambiguous identification of single base mismatches in nucleic acid sequences is
      of great importance in nucleic acid detection assays. However, ambiguities are
      often encountered with, and therefore, a strategy for attaining substantially
      large enhancement of mismatch discrimination has been worked upon in this study.
      Short single-stranded peptide nucleic acid (PNA) and deoxyribonucleic acid (DNA)
      sensor probes that are immobilized onto gold nanoparticle (AuNP) modified Au(111)
      surface have been applied for target DNA detection. It will be shown that while
      both PNA and the analogous DNA probes exhibit generally better target detection
      abilities on the AuNP-modified Au(111) surface (elicited from fluorescence-based
      measurement of on-surface Tm values), compared to the bare Au(111) surface, PNA
      supersedes DNA, for all sizes of AuNPs (10, 50, and 90 nm) applied, with the
      difference being quite drastic in the case of the smallest 10 nm AuNP. It is
      found that while the AuNP curvature plays a pivotal role in target detection
      abilities of the PNA probes, the changes in the surface roughness caused by AuNP
      treatment do not exert any significant influence. This study also presents a
      means for preparing PNA-AuNP hybrids without altering PNA functionality and
      without AuNP aggregation by working with the surface-affixed AuNPs. 

PMID- 23978257
TI  - A new approach to measuring protein backbone protection with high spatial
      resolution using H/D exchange and electron capture dissociation.
AB  - Inadequate spatial resolution remains one of the most serious limitations of
      hydrogen/deuterium exchange-mass spectrometry (HDX-MS), especially when applied
      to larger proteins (over 30 kDa). Supplementing proteolytic fragmentation of the
      protein in solution with ion dissociation in the gas phase has been used
      successfully by several groups to obtain near-residue level resolution. However,
      the restrictions imposed by the LC-MS/MS mode of operation on the data
      acquisition time frame makes it difficult in many cases to obtain a signal-to
      noise ratio adequate for reliable assignment of the backbone amide protection
      levels at individual residues. This restriction is lifted in the present work by
      eliminating the LC separation step from the workflow and taking advantage of the
      high resolving power and dynamic range of a Fourier transform ion cyclotron
      resonance-mass spectrometer (FTICR-MS). A residue-level resolution is
      demonstrated for a peptic fragment of a 37 kDa recombinant protein (N-lobe of
      human serum transferrin), using electron-capture dissociation as an ion
      fragmentation tool. The absence of hydrogen scrambling in the gas phase prior to
      ion dissociation is verified using redundant HDX-MS data generated by FTICR-MS.
      The backbone protection pattern generated by direct HDX-MS/MS is in excellent
      agreement with the known crystal structure of the protein but also provides
      information on conformational dynamics, which is not available from the static X
      ray structure. 

PMID- 23978258
TI  - Nitric oxide synthase expression correlates with death in an experimental mouse
      model of dengue with CNS involvement.
AB  - BACKGROUND: The clinical presentation of dengue is classified by the World Health
      Organization into dengue without warning signs, dengue with warning signs and
      severe dengue. Reports of neurological disease caused by Dengue virus (DENV) are
      becoming frequent, with symptoms that include reduced consciousness, severe
      headache, neck stiffness, focal neurological signs, tense fontanelle and
      convulsions. However, the immune mechanisms involved in neurovirulence remain
      poorly understood. Here we present a mouse model in which one genotype of DENV is
      inoculated by the intracranial route and infects C57/BL6 mice and replicates in
      the brain, causing death of mice. METHODS: Mice were infected with different
      serotypes/genotypes of DENV by the intracranial route to evaluate viral
      replication, host cytokine and nitric oxide synthase 2 (Nos2) expression in the
      brain via real-time PCR. Histological analysis of the brain tissues was also
      performed. An analysis of which cells were responsible for the expression of
      cytokines and Nos2 was performed using flow cytometry. Survival curves of
      infected animals were also generated RESULTS: DENV 3 genotype I infected mice and
      replicated in the brain, causing death in our murine model. The increased levels
      of NOS2 could be the cause of the death of infected mice, as viral replication
      correlates with increased Nos2 and cytokine expression in the brain of C57BL/6
      mice. In Nos2-/- mice that were infected with DENV, no clinical signs of
      infection were observed and cytokines were expressed at low levels, with the
      exception of interferon gamma (Ifng). Additionally, the Ifng-/- mice infected
      with DENV exhibited a severe and lethal disease, similar to the disease observed
      in C57BL/6 mice, while the DENV- infected Nos2-/- mice did not display increased
      mortality. Analyses of the brains from infected C57BL/6 mice revealed neuronal
      degeneration and necrosis during histopathologic examination. IFNg and NOS2 were
      produced in the brains of infected mice by CD4+ T cells and macrophages,
      respectively. CONCLUSION: The neurovirulence of DENV 3 genotype I is associated
      with a deleterious role of NOS2 in the brain, confirming this murine model as an
      appropriate tool to study DENV neurovirulence.

PMID- 23978259
TI  - A mouse with humanized liver as an animal model for predicting drug effects and
      for studying hepatic viral infection: where to next?
AB  - INTRODUCTION: The mouse is a common model used in evaluating drug metabolism and
      hepatitis infectivity. However, these models have limited value due to species
      difference in hepatic functions, leading to the creation of the chimeric mouse 12
      years ago. These models were unique in that their hepatocytes had been replaced
      with human (hu) hepatocytes (dubbed the 'first-generation chimeric mouse'). Since
      then, the chimeric mouse has become a practical tool for this area of studies.
      However, some shortcomings have also been recognized. One major shortcoming is
      that the mouse cannot mimic hu-liver diseases due to immunodeficiency and also it
      is unable to provide sufficient amounts of blood for analysis compared to the
      rat. There are also issues around donor-to-donor variability of hu-hepatocytes
      such as variable engraftment efficiency. AREAS COVERED: This review provides the
      current status of the first-generation chimeric mouse. Furthermore, the authors
      review studies intended to create a 'second-generation of the chimeric mouse' in
      which inflammation/immune-response cells as well as hepatocytes are humanized. A
      brief comment is also made on studies aiming at producing chimeric rats. Finally,
      the authors consider induced pluripotent stem cells (iPS cells) as new sources of
      hu-hepatocytes. EXPERT OPINION: The authors believe that the current rapid
      progress in the field of biotechnology should enable us to create a mouse model
      with a humanized liver that is made by iPS-derived hu-hepatocytes and hu-immune
      cells. This development will provide researchers with a model that will be able
      to effectively mimic human liver disease under experimental conditions.

PMID- 23978261
TI  - Speciation of platinum(IV) in nitric acid solutions.
AB  - The speciation of platinum(IV) ions in nitric acid (6-15.8 M) solutions of
      H2[Pt(OH)6] has been studied by (195)Pt NMR and Raman spectroscopy. Series of
      aqua-hydroxo-nitrato complexes [Pt(L)(x)(NO3)(6-x)] (L = H2O or OH(-); x = 0,
      ..., 6) were found to exist in such solutions. The pair additivity model of
      chemical shifts and statistical theory were used to assign signals in NMR spectra
      to particular [Pt(L)(x)(NO3)(6-x)] species. Mononuclear hexanitratoplatinates(IV)
      have been isolated in solid state in substantial yield as pyridinium salt
      (PyH)2[Pt(NO3)6] and characterized by single-crystal X-ray diffraction. Aging of
      the platinum nitric acid solutions for more than 5-6 h results in oligomerization
      of [Pt(L)(x)(NO3)(6-x)] species and the formation of oligonuclear aqua-hydroxo
      nitrato complexes with OH(-) and NO3(-) bridging ligands. Oligomeric platinum(IV)
      complexes with two and four nuclei were unambiguously detected by NMR on (195)Pt 
      enriched samples. Oligomers with even higher nuclearity were also detected.
      Dimeric anions [Pt2(MU-OH)2(NO3)8](2-) have been isolated as single crystals of
      tetramethylammonium salt and characterized by X-ray diffraction.

PMID- 23978260
TI  - Genomic characterization of JG068, a novel virulent podovirus active against
      Burkholderia cenocepacia.
AB  - BACKGROUND: As is true for many other antibiotic-resistant Gram-negative
      pathogens, members of the Burkholderia cepacia complex (BCC) are currently being
      assessed for their susceptibility to phage therapy as an antimicrobial treatment.
      The objective of this study was to perform genomic and limited functional
      characterization of the novel BCC phage JG068 (vB_BceP_JG068). RESULTS: JG068 is
      a podovirus that forms large, clear plaques on Burkholderia cenocepacia K56-2.
      Host range analysis indicates that this phage can infect environmental, clinical,
      and epidemic isolates of Burkholderia multivorans, B. cenocepacia, Burkholderia
      stabilis, and Burkholderia dolosa, likely through interaction with the host
      lipopolysaccharide as a receptor. The JG068 chromosome is 41,604 base pairs (bp)
      in length and is flanked by 216 bp short direct terminal repeats. Gene expression
      originates from both host and phage promoters and is in the forward direction for
      all 49 open reading frames. The genome sequence shows similarity to Ralstonia
      phage phiRSB1, Caulobacter phage Cd1, and uncharacterized genetic loci of blood
      disease bacterium R229 and Burkholderia pseudomallei 1710b. CoreGenesUniqueGenes
      analysis indicates that JG068 belongs to the Autographivirinae subfamily and
      phiKMV-like phages genus. Modules within the genome encode proteins involved in
      DNA-binding, morphogenesis, and lysis, but none associated with pathogenicity or
      lysogeny. Similar to the signal-arrest-release (SAR) endolysin of phiKMV,
      inducible expression of the JG068 SAR endolysin causes lysis of Escherichia coli
      that is dependent on the presence of an N-terminal signal sequence. In an in vivo
      assay using the Galleria mellonella infection model, treatment of B. cenocepacia
      K56-2-infected larvae with JG068 results in a significant increase in larval
      survival. CONCLUSIONS: As JG068 has a broad host range, does not encode virulence
      factors, is obligately lytic, and has activity against an epidemic B. cenocepacia
      strain in vivo, this phage is a highly promising candidate for BCC phage therapy
      development.

PMID- 23978262
TI  - Graphene for true Ohmic contact at metal-semiconductor junctions.
AB  - The rectifying Schottky characteristics of the metal-semiconductor junction with
      high contact resistance have been a serious issue in modern electronic devices.
      Herein, we demonstrated the conversion of the Schottky nature of the Ni-Si
      junction, one of the most commonly used metal-semiconductor junctions, into an
      Ohmic contact with low contact resistance by inserting a single layer of
      graphene. The contact resistance achieved from the junction incorporating
      graphene was about 10(-8) ~ 10(-9) Omega cm(2) at a Si doping concentration of
      10(17) cm(-3).

PMID- 23978263
TI  - Efficacy of Berberis vulgaris aqueous extract on viability of Echinococcus
      granulosus protoscolices.
AB  - BACKGROUND: Surgery is one of the best choices for the treatment of hydatidosis.
      To prevent the secondary infection, it is essential to use effective scolicidal
      agents during surgery for hydatid cyst. Up to now, no effective and safe agent
      has been identified for this purpose. Berberis vulgaris called "Zereshk" in
      Persian has been traditionally used as a herbal remedy for the treatment of
      different complaints. Many studies have shown that Berberis vulgaris has
      antibacterial, antifungal, and antiparasitic effects. METHODS: In our study, the
      scolicidal effect of barberry with different concentrations (0.5, 1, 2, and 4
      mg/ml diluted form) and at different exposure times (5, 15, and 30 min) was
      evaluated. For this purpose, we obtained sheep liver hydatid cysts from a
      slaughterhouse. Viability of protoscolices was assessed by 0.1% Eosin staining.
      Normal saline and hypertonic saline were used as negative and positive controls,
      respectively. RESULTS: All the different concentrations of Berberis vulgaris
      aqueous extracts had scolicidal effect. The strongest effect was observed to be
      in 4 mg/ml concentration, which acted as positive control. Scolicidal activity of
      2 mg/ml dilution was close to 4 mg/ml and the least scolicidal effect was
      observed in 0.5 mg/ml. Scolicidal activity of extracts had significant
      differentiation between 5th and 30th min of exposure. CONCLUSION: The scolicidal
      activity was very effective in low concentration (4 mg/ml) and short exposure
      time (5 min). Therefore, after being examined in vivo and additional experiments,
      it may be used as a suitable and effective scolicidal in surgery.

PMID- 23978264
TI  - Microsporidial keratitis after collagen cross-linking.
AB  - PURPOSE: To report a case of infectious keratitis due to Microsporidium after
      collagen crosslinking (CXL). METHODS: A 36-year-old man presented with a 3-day
      history of pain, redness and diminution of vision in his left eye. The patient
      had received CXL for keratoconus in the left eye 6 days prior to presentation.
      Best-corrected visual acuity (BCVA) was 20/25 OD and counting fingers OS. Slit
      lamp examination of the left eye showed a central epithelial defect measuring and
      multiple stromal infiltrates. RESULTS: Gram and Giemsa staining of corneal
      scrapings showed spores characteristic of Microsporidia. Hourly 0.5% moxifloxacin
      eye drops, 0.5% moxifloxcain eye ointment nocte and oral albendazole 400 mg twice
      daily were commenced. Corneal debridement was performed twice during the first
      week. At the end of 6 weeks BCVA was 20/60 in the left eye. CONCLUSIONS:
      Microsporidial infection can be confirmed on microbiological examination. Our
      case responded well to medical treatment alone.

PMID- 23978266
TI  - High performance composites with active stiffness control.
AB  - High performance carbon fiber reinforced composites with controllable stiffness
      could revolutionize the use of composite materials in structural applications.
      Here we describe a structural material, which has a stiffness that can be
      actively controlled on demand. Such a material could have applications in
      morphing wings or deployable structures. A carbon fiber reinforced-epoxy
      composite is described that can undergo an 88% reduction in flexural stiffness at
      elevated temperatures and fully recover when cooled, with no discernible damage
      or loss in properties. Once the stiffness has been reduced, the required
      deformations can be achieved at much lower actuation forces. For this proof-of
      concept study a thin polyacrylamide (PAAm) layer was electrocoated onto carbon
      fibers that were then embedded into an epoxy matrix via resin infusion. Heating
      the PAAm coating above its glass transition temperature caused it to soften and
      allowed the fibers to slide within the matrix. To produce the stiffness change
      the carbon fibers were used as resistance heating elements by passing a current
      through them. When the PAAm coating had softened, the ability of the interphase
      to transfer load to the fibers was significantly reduced, greatly lowering the
      flexural stiffness of the composite. By changing the moisture content in PAAm
      fiber coating, the temperature at which the PAAm softens and the composites
      undergo a reduction in stiffness can be tuned. 

PMID- 23978265
TI  - A universal DNA-based protein detection system.
AB  - Protein immune detection requires secondary antibodies which must be carefully
      selected in order to avoid interspecies cross-reactivity, and is therefore
      restricted by the limited availability of primary/secondary antibody pairs. Here
      we present a versatile DNA-based protein detection system using a universal
      adapter to interface between IgG antibodies and DNA-modified reporter molecules.
      As a demonstration of this capability, we successfully used DNA nano-barcodes,
      quantum dots, and horseradish peroxidase enzyme to detect multiple proteins using
      our DNA-based labeling system. Our system not only eliminates secondary
      antibodies but also serves as a novel method platform for protein detection with
      modularity, high capacity, and multiplexed capability. 

PMID- 23978267
TI  - Pharmacokinetics modeling of exogenous glucagon in type 1 diabetes mellitus
      patients.
AB  - BACKGROUND: Insulin-induced hypoglycemia is as a critical barrier in the
      treatment of type 1 diabetes mellitus patients and may lead to unconsciousness,
      brain damage, or even death. Clinically, glucagon is used as a rescue drug to
      treat severe hypoglycemic episodes. More recently, in a bihormonal closed-loop
      glucose control, glucagon has been used subcutaneously along with insulin for
      protection against hypoglycemia. In this context, small doses of glucagon are
      frequently administered. The efficacy and safety of such systems, however,
      require precise information on the pharmacokinetics of the glucagon transport
      from the administrative site to the circulation, which is currently lacking. The
      goal of this work is to address this need by developing and validating a
      mathematical model of exogenous glucagon transport to the plasma. MATERIALS AND
      METHODS: Eight pharmacokinetic models with various levels of complexity were
      fitted to nine clinical datasets. An optimal model was chosen in two consecutive
      steps. At Step 1, all models were screened for parameter identifiability
      (discarding the unidentifiable candidates). At Step 2, the remaining models are
      compared based on Bayesian information criterion. RESULTS: At Step 1, two models
      were removed for higher parameter fractional SDs. Another three were discarded
      for location of their optimal parameters on the parameter search boundaries. At
      Step 2, an optimal model was selected based on the Bayesian information
      criterion. It has a simple linear structure, assuming that glucagon is injected
      into one compartment, from where it enters a pool for a slower release into a
      third, plasma compartment. In the first and third compartments, glucagon is
      cleared at a rate proportional to its concentration. CONCLUSIONS: A linear
      kinetic model of glucagon intervention has been developed and validated. It is
      expected to provide guidance for glucagon delivery and the construction of
      preclinical simulation testing platforms.

PMID- 23978268
TI  - Suppression and interpersonal harmony: a cross-cultural comparison between
      Chinese and European Americans.
AB  - Based on Markus and Kitayama's (1991) theory, this study was conducted to examine
      whether the association between emotional suppression and interpersonal harmony
      would be moderated by cultural group (i.e., Chinese and European Americans) and
      an Asian cultural value (i.e., emotional self-control). A total of 451 college
      students (205 Chinese and 246 European Americans) participated in this study. As
      expected, results indicated that the association between emotional suppression
      and interpersonal harmony was significantly positive for Chinese but not
      significant for European Americans. Similarly, when emotional self-control was
      examined as a moderator, the results still confirmed our hypotheses. That is, the
      association between emotional suppression and interpersonal harmony was
      significantly positive for those with stronger endorsement of emotional self
      control but not for those with weaker endorsement of emotional self-control.
      Furthermore, we examined whether the above results could be replicated when
      forbearance (a construct similar to suppression) and distress disclosure (a
      construct opposite to suppression) were examined. The results showed the same
      pattern for forbearance and distress disclosure when cultural group or emotional
      self-control served as the moderator. The convergence of findings increased the
      robustness of our results. Finally, our data suggest that individuals from
      Eastern, interdependent cultures (e.g., Chinese) tend to value emotional
      suppression to preserve interpersonal harmony; individuals from Western,
      independent cultures may or may not necessarily suppress their emotions for this
      purpose. A comprehensive understanding of the different meanings of a specific
      strategy (i.e., emotional suppression) in different cultural contexts is
      important to promote effective cross-cultural counseling.

PMID- 23978269
TI  - Ultrasound-guided percutaneous laser ablation of papillary thyroid
      microcarcinoma: a feasibility study on three cases with pathological and
      immunohistochemical evaluation.
AB  - BACKGROUND: Ultrasound-guided thermal laser ablation (LA) is a nonsurgical
      technique that has been proposed, but not fully assessed, for papillary thyroid
      microcarcinoma (PTMC) treatment. The objectives of this study were to evaluate
      the clinical feasibility of LA on PTMC as a primary treatment and to prove
      histologically the absence of residual viable tumor after LA procedure. METHODS:
      Three patients with a Thy 6 diagnosis at fine-needle aspiration cytology with a
      single PTMC smaller than 10 mm volunteered after full explanation of the
      protocol. At ultrasound examination, patients had no extrathyroid extension and
      no evidence of lymph node metastasis. Patients underwent percutaneous ultrasound
      assisted LA of the PTMC in the operating room under general anesthesia. One 300
      MUm plane-cut optic fiber was inserted through the sheath of 21G Chiba needle,
      exposing 5 mm of the nude fiber in direct contact with tumor tissue, and
      connected with a laser source operating at 1.064 MUm with 3 W output power. Total
      energy delivery was 1800 J. The surgeon directly started a standard total
      thyroidectomy. During surgical inspection, no remarkable laser sign was observed
      in the muscles, the perithyroidal tissues, or the recurrent laryngeal nerves.
      RESULTS: Conventional histology showed destructured and carbonized tissue. Lack
      of vitality was demonstrated by complete loss of TTF1 and antimitochondria
      antibody expression in the whole ablated area and in the rim of normal tissue
      surrounding the tumor. BRAF V600E mutation was detected in cases 1 and 2.
      Furthermore, in cases 2 and 3, incidental papillary microfoci were found. A lymph
      node micrometastasis (200 MUm) was observed in case 2. CONCLUSIONS: This study
      demonstrates that percutaneous LA is technically feasible for complete PTMC
      destruction. Now, LA may be useful in selected patients with PTMC, either when
      the surgeon or a patient refuses surgery, or when the patient is at high risk for
      an operation. LA may become a primary choice of treatment for PTMC only if future
      new knowledge would permit preoperative recognition of multifocality and lymph
      node metastasis.

PMID- 23978270
TI  - Challenges with QuantiFERON-TB Gold assay for large-scale, routine screening of
      U.S. healthcare workers.
AB  - RATIONALE: North American occupational health programs that switched from the
      tuberculin skin test (TST) to IFN-gamma release assays for latent tuberculosis
      screening are reporting challenges with interpretation of serial testing results
      in healthcare workers (HCWs). However, limited data exist on the reproducibility
      of serial IFN-gamma release assay results in low-risk HCWs. OBJECTIVES: To
      evaluate the short-term reproducibility of QuantiFERON-TB Gold In-Tube (QFT) in a
      large cohort of HCWs and to define a QFT cutoff yielding a conversion rate
      equivalent to historical TST rates. METHODS: We retrospectively evaluated the QFT
      results from HCWs with two or more QFT tests performed between June 2008 and July
      2010 at an academic institution. Outcome measures were proportions of
      reproducibility, quantitative results, and conversion rates with alternate QFT
      cutoffs. MEASUREMENTS AND MAIN RESULTS: A total of 9,153 HCWs with two or more
      QFT tests were included in the analysis. Of 8,227 individuals with a negative
      result, 4.4% (n = 361) converted their QFT result over 2 years. A total of 261
      (72.3%) of the HCWs with conversions underwent repeat short-term testing after
      the first positive result with 64.8% reverting (n = 169). An IFN-gamma cutoff of
      5.3 IU/ml or higher (manufacturer's cutoff is >=0.35 IU/ml) yielded a conversion
      rate of 0.4%, equal to our institution's historical TST conversion rate.
      CONCLUSIONS: The manufacturer's definition of QFT conversion results in an
      inflated conversion rate that is incompatible with our low-risk setting. A
      significantly higher QFT cutoff value is needed to match the historical TST
      conversion rate. Nonreproducible conversions in most converters suggested false
      positive results.

PMID- 23978272
TI  - Titration of free hydroxyl and strained siloxane sites on silicon dioxide with
      fluorescent probes.
AB  - A technique enabling the detection and quantification of low density sites on
      planar SiO2 surfaces is demonstrated. Fluorescent probes are used to titrate free
      hydroxyl and strained siloxane sites on the surface of amorphous SiO2 substrates
      in vacuum. The titration of free hydroxyl sites was performed to validate the
      method and to provide a reference for the measurement of the strained siloxane
      site density. Perylene derivatives with different functional groups are
      chemisorbed onto the surface sites, enabling in situ photoluminescence (PL)
      measurements of the bound fluorophores. An amine functional group is used to
      selectively titrate strained siloxane sites, while an alcohol group is used for
      the titration of free hydroxyl sites. Emission intensity was found to be
      nonlinear with coverage for bound fluorophore densities greater than 0.1 nm(-2),
      necessitating the removal of molecules from the surface into a solution to obtain
      accurate density measurements. For lower densities, the coverage of bound
      fluorophores can be estimated directly from in situ PL measurements. The measured
      areal densities of bound fluorophores after titrating free hydroxyl sites are in
      good agreement with literature values for the densities of such sites on high
      surface area silica. PL measurements of SiO2 surfaces titrated with an amine
      derivative of perylene indicate that strained siloxane sites exist for vacuum
      pretreatment temperatures of 300  degrees C and increase with increasing
      pretreatment temperature. Densities of strained siloxane sites on the silica
      surface are estimated at 0.004-0.02 nm(-2) for pretreatment temperatures of 300
      700  degrees C, demonstrating the sensitivity of this technique. 

PMID- 23978273
TI  - Sensitivity limits of continuous wave cavity ring-down spectroscopy.
AB  - An optimized nonlinear least-squares fit algorithm for data processing in cavity
      ring-down spectroscopy (CRDS) is discussed, which improves the calculation
      efficiency substantially over using a general purpose fitting package.
      Theoretical absorption sensitivity limits for both the detector noise and the
      shot noise limited situations are derived and compared with experimental results.
      The effect of limiting the bandwidth of detection system on ring-down signal is
      discussed and compared with real ring-down data. The optimal trigger level and
      fitting interval are obtained for continuous wave cavity ring-down spectroscopy
      (cw-CRDS) in both the detector noise and shot noise limits, with the resulting
      sensitivity in units of cm(-1) per (Hz(1/2)) derived. Interestingly, it is found
      that the optimized shot noise limited sensitivity in cw-CRDS method is, in
      principle, comparable with the ultimate sensitivity of noise-immune cavity
      enhanced optical heterodyne molecular spectroscopy (NICE-OHMS). 

PMID- 23978271
TI  - 24-hour central aortic systolic pressure and 24-hour central pulse pressure are
      related to diabetic complications in type 1 diabetes - a cross-sectional study.
AB  - BACKGROUND: Non-invasive measurements of 24 hour ambulatory central aortic
      systolic pressure (24 h-CASP) and central pulse pressure (24 h-CPP) are now
      feasible. We evaluate the relationship between 24 h central blood pressure and
      diabetes-related complications in patients with type 1 diabetes. METHODS: The
      study was cross-sectional, including 715 subjects: 86 controls (C), 69 patients
      with short diabetes duration (< 10 years), normoalbuminuria (< 30 mg/24 h)
      without receiving antihypertensive treatment (SN), 211 with longstanding diabetes
      (>= 10 years) and normoalbuminuria (LN), 163 with microalbuminuria (30-299 mg/24
      h) (Mi) and 186 with macroalbuminuria (> 300 mg/24 h) (Ma).24 h-CASP and 24 h-CPP
      was measured using a tonometric wrist-watch-like device (BPro, HealthStats,
      Singapore) and derived using N-point moving average. RESULTS: In C, SN, LN, Mi
      and Ma mean +/- SD 24 h-CASP was: 114 +/- 17, 115 +/- 13, 121 +/- 13, 119 +/- 16
      and 121 +/- 13 mmHg (p < 0.001); and 24 h-CPP: 38 +/- 8, 38 +/- 7, 44 +/- 10, 46
      +/- 11 and 46 +/- 11 mmHg, (p < 0.001).Following rigorous adjustment (24 h mean
      arterial pressure and conventional risk factors), 24 h-CASP and 24 h-CPP
      increased with diabetes, albuminuria degree, previous cardiovascular disease
      (CVD), retinopathy and autonomic dysfunction (p <= 0.031).Odds ratios per 1
      standard deviation increase in 24 h-CASP, 24 h-CPP and 24 h systolic blood
      pressure (24 h-SBP) were for CVD: 3.19 (1.68-6.05), 1.43 (1.01-2.02) and 2.39
      (1.32-4.33), retinopathy: 4.41 (2.03-9.57), 1.77 (1.17-2.68) and 3.72 (1.85-7.47)
      and autonomic dysfunction: 3.25 (1.65-6.41), 1.64 (1.12-2.39) and 2.89 (1.54
      5.42). CONCLUSIONS: 24 h-CASP and 24 h-CPP was higher in patients vs. controls
      and increased with diabetic complications independently of covariates.
      Furthermore, 24 h-CASP was stronger associated to complications than 24 h-SBP.The
      prognostic significance of 24 h-CASP and 24 h-CPP needs to be determined in
      follow-up studies. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT01171248.

PMID- 23978274
TI  - Toward unraveling grape tannin composition: application of online hydrophilic
      interaction chromatography * reversed-phase liquid chromatography-time-of-flight
      mass spectrometry for grape seed analysis.
AB  - Despite the significant importance of tannins in viticulture and enology,
      relatively little is known about the detailed chemical composition of these
      molecules. This is due to challenges associated with the accurate analytical
      determination of the highly structurally diverse proanthocyanidins which comprise
      tannins. In this contribution, we address this limitation by demonstrating how
      online comprehensive two-dimensional liquid chromatography (LC * LC) coupled to
      high resolution mass spectrometry (HR-MS) can be exploited as a powerful
      analytical approach for the detailed characterization of grape seed tannins.
      Hydrophilic interaction chromatography (HILIC) and reversed-phase liquid
      chromatography (RP-LC) were employed in the two dimensions to provide
      complementary information in terms of separation according to hydrophilicity and
      hydrophobicity, respectively. Online coupling of HILIC * RP-LC with fluorescence
      detection and electrospray ionization MS delivered high resolution analysis in a
      practical analysis time, while allowing selective detection and facilitating
      compound identification. Time-of-flight (TOF) MS provided high acquisition rates
      and sensitivity coupled to accurate mass information, which allowed detection of
      procyanidins up to a degree of polymerization (DP) of 16 and a degree of
      galloylation up to 8 in a red grape seed extract. This analytical methodology
      promises to shed new light on these important grape constituents and potentially
      on their evolution during wine production. 

PMID- 23978275
TI  - Impact of preoperative patient education on prevention of postoperative
      complications after major visceral surgery: study protocol for a randomized
      controlled trial (PEDUCAT trial).
AB  - BACKGROUND: In line with the growing number of surgical procedures being
      performed worldwide, postoperative complications are also increasing
      proportionately. Prevention of these postoperative complications is a high
      medical priority. Preoperative education of patients, including provision of
      preparatory information about the correct behavior after surgery, could improve
      the postoperative outcome, but the evidence for this is inconclusive. The aim of
      the PEDUCAT trial is to evaluate the feasibility and the impact of preoperative
      patient education on postoperative morbidity, mortality and quality of life in
      patients scheduled for elective major visceral surgery. METHODS/DESIGN: PEDUCAT
      is designed as a cluster-randomized controlled pilot study. The experimental
      group will visit a standardized preoperative seminar to learn how best to behave
      after surgery in addition to being given a standard information brochure, whereas
      the control group will only receive the information brochure. Outcome measures
      such as postoperative morbidity, postoperative pain, postoperative anxiety and
      depression, patient satisfaction, quality of life, length of hospital stay and
      postoperative mortality will be evaluated. Statistical analysis will be based on
      the intention-to-treat population. Analysis of covariance will be applied for the
      intervention group comparison, adjusting for age, center and quality of life
      before surgery. This is a pilot study to show the feasibility of the concept.
      Nevertheless, the planned sample size of n = 204 is large enough to show an
      effect with power of 90% and a significance level of 5%. TRIAL REGISTRATION:
      German Clinical Trial Register number: DRKS00004226.

PMID- 23978276
TI  - Differential treatment of hypertension by primary care providers and hypertension
      specialists in a barber-based intervention trial to control hypertension in Black
      men.
AB  - Black men have less physician contact than other groups and thus lower rates of
      hypertension treatment and control. In the Barber-Assisted Reduction in Blood
      Pressure among Ethnic Residents trial, hypertension control in 8 active
      intervention barbershops where barbers offered blood pressure (BP) checks with
      haircuts and motivated black male patrons with high BP to seek provider follow-up
      showed a small improvement over that in 7 comparison shops where patrons received
      hypertension pamphlets but not barber-BP checks. Undertreatment of hypertension,
      which is common in primary care, may have impacted the outcomes. Thus, in patrons
      with a baseline systolic BP of >=140 mm Hg and 10-month follow-up including BP
      and medication data, we performed post hoc comparison of systolic BP reduction
      between comparison-arm patrons (n = 68) treated by primary care providers (PCPs)
      with (1) intervention-arm patrons (n = 37) treated by PCPs or (2) intervention
      arm patrons (n = 33) who lacked access to PCPs and were treated by hypertension
      specialist physicians serving as safety net providers. The latter group had
      higher baseline systolic BP than the others (162 +/- 3 vs 155 +/- 2 and 154 +/- 2
      mm Hg, respectively, p <0.01). After adjustment for baseline systolic BP and
      other covariates, systolic BP reduction was 21 +/- 4 mm Hg greater than in the
      comparison group (p <0.0001), when barbers referred patrons to hypertension
      specialists but was no different when they referred to PCPs (4 +/- 4 mm Hg, p =
      0.31). Specialist-treated patrons received more BP medication and different
      classes of medication than PCP-treated patrons. In conclusion, the barber-based
      intervention-if connected directly to specialty-level medical care-could have a
      large public health impact on hypertensive disease in black men.

PMID- 23978277
TI  - Quality of life in patients with low-risk prostate cancer. A comparative
      retrospective study: brachytherapy versus robot-assisted laparoscopic
      prostatectomy versus active surveillance.
AB  - PURPOSE: To investigate the quality of life (QoL) after different treatment
      modalities for low-risk prostate cancer, including brachytherapy, robot-assisted
      laparoscopic prostatectomy (RALP), and active surveillance (AS) with validated
      questionnaires. MATERIALS AND METHODS: From a prospective database, we selected a
      total of 144 men with low-grade localized prostate cancer including 65 (45.1%)
      patients with RALP, 29 (20.2%) with brachytherapy, and 50 (34.7%) whose cancer
      was managed with AS. QoL was routinely evaluated with validated questionnaires:
      The European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire Core 30 (EORTC-QLQ-C30), EORTC-QLQ-Prostate Module (PR)25,
      International Index of Erectile Function (IIEF)-15, International Consultation on
      Incontinence Questionnaire Short Form (ICIQ-SF) with a minimum follow-up of 1
      year. RESULTS: In comparison with baseline scores, the brachytherapy group showed
      a significant decrease of QoL domain scores of voiding complaints (P=0.010), use
      of incontinence aids (P=0.011), sexual functioning domain (P=0.011), and erectile
      function (P<=0.001). In the RALP group, sexual function (P<=0.001), incontinence
      (P<=0.001), and erectile function were significantly affected. A decrease in
      sexual function was observed in 71% of men after RALP and 59% after
      brachytherapy. In 30% of men under AS, a decrease of erectile function score
      during follow-up was reported. Overall, no significant decrease in general QoL
      was observed neither for men under AS nor for men treated by brachytherapy or
      RALP. Clinical factors such as age, prostate size, prostate-specific antigen
      level, and nerve preservation during RALP were nonpredictive of overall QoL after
      treatment for the individual patient (P=0.676). CONCLUSION: Patients with low
      risk prostate cancer who are treated with brachytherapy or RALP report
      deterioration of QoL of specific domains such as voiding, continence, and sexual
      functioning in comparison with AS patients. A decrease of erectile function was
      also observed during AS. Overall QoL was similar for all three treatments
      options.

PMID- 23978278
TI  - Influence of different planting seasons of six leaf vegetables on residues of
      five pesticides.
AB  - To investigate the influence of different planting seasons on the dissipation of
      pesticides, field experiments of thiophanate-methyl, metalaxyl, fluazifop-P
      butyl, chlorpyrifos, and lambda-cyhalothrin on six crops including pakchoi, rape,
      crown daisy, amaranth, spinach, and lettuce were designed and conducted. In this
      study, a high-performance liquid chromatography and electrospray ionization
      tandem mass spectrometer with multiple reaction monitoring was used to
      simultaneously determine thiophanate-methyl and its metabolite carbendazim,
      metalaxyl, and fluazifop-P-butyl in various samples; gas chromatography with an
      electron capture detector was used to detect chlorpyrifos and lambda-cyhalothrin.
      The limits of quantitation (LOQs) of these six pesticides were in the range of
      0.001-0.01 mg kg(-1) for all samples, and the average recoveries of all
      pesticides ranged from 60.1 to 119.1% at 0.01 and 0.1 mg kg(-1) spiked levels.
      The relative standard deviation (RSD) ranged from 1.1 to 13.9%. All maximal
      concentrations of the six pesticides in six leaf vegetables in autumn were higher
      than in summer in Beijing. For most pesticides half-lives in autumn were longer
      than in summer. The results showed that the initial concentration, maximal
      concentration, and half-lives of pesticides were influenced not only by
      environmental factors such as light, heat, moisture, and rainy climate but also
      by plant matrices. 

PMID- 23978279
TI  - Plasticity of primary and secondary growth dynamics in Eucalyptus hybrids: a
      quantitative genetics and QTL mapping perspective.
AB  - BACKGROUND: The genetic basis of growth traits has been widely studied in forest
      trees. Quantitative trait locus (QTL) studies have highlighted the presence of
      both stable and unstable genomic regions accounting for biomass production with
      respect to tree age and genetic background, but results remain scarce regarding
      the interplay between QTLs and the environment. In this study, our main objective
      was to dissect the genetic architecture of the growth trajectory with emphasis on
      genotype x environment interaction by measuring primary and secondary growth
      covering intervals connected with environmental variations. RESULTS: Three
      different trials with the same family of Eucalyptus urophylla x E. grandis
      hybrids (with different genotypes) were planted in the Republic of Congo,
      corresponding to two QTL mapping experiments and one clonal test. Height and
      radial growths were monitored at regular intervals from the seedling stage to
      five years old. The correlation between growth increments and an aridity index
      revealed that growth before two years old (r = 0.5; 0.69) was more responsive to
      changes in water availability than late growth (r = 0.39; 0.42) for both height
      and circumference. We found a regular increase in heritability with time for
      cumulative growth for both height [0.06 - 0.33] and circumference [0.06 - 0.38].
      Heritabilities for incremental growth were more heterogeneous over time even if
      ranges of variation were similar (height [0-0.31]; circumference [0.19 to 0.48]).
      Within the trials, QTL analysis revealed collocations between primary and
      secondary growth QTLs as well as between early growth increments and final growth
      QTLs. Between trials, few common QTLs were detected highlighting a strong
      environmental effect on the genetic architecture of growth, validated by
      significant QTL x E interactions. CONCLUSION: These results suggest that early
      growth responses to water availability determine the genetic architecture of
      total growth at the mature stage and highlight the importance of considering
      growth as a composite trait (such as yields for annual plants) for a better
      understanding of its genetic bases.

PMID- 23978280
TI  - Research on vaccines and antimicrobials during pregnancy: challenges and
      opportunities.

PMID- 23978281
TI  - Stabilizing small molecules on metal oxide surfaces using atomic layer
      deposition.
AB  - Device lifetimes and commercial viability of dye-sensitized solar cells (DSSCs)
      and dye-sensitized photoelectrosynthesis cells (DSPECs) are dependent on the
      stability of the surface bound molecular chromophores and catalysts. Maintaining
      the integrity of the solution-metal oxide interface is especially challenging in
      DSPECs for water oxidation where it is necessary to perform high numbers of
      turnovers, under irradiation in an aqueous environment. In this study, we
      describe the atomic layer deposition (ALD) of TiO2 on nanocrystalline TiO2
      prefunctionalized with the dye molecule [Ru(bpy)2(4,4'-(PO3H2)bpy)](2+) (RuP) as
      a strategy to stabilize surface bound molecules. The resulting films are over an
      order of magnitude more photostable than untreated films and the desorption rate
      constant exponentially decreases with increased thickness of ALD TiO2 overlayers.
      However, the injection yield for TiO2-RuP with ALD TiO2 also decreases with
      increasing overlayer thickness. The combination of decreased injection yield and
      95% quenched emission suggests that the ALD TiO2 overlayer acts as a competitive
      electron acceptor from RuP*, effectively nonproductively quenching the excited
      state. The ALD TiO2 also increases back electron transfer rates, relative to the
      untreated film, but is independent of overlayer thickness. The results for TiO2
      RuP with an ALD TiO2 overlayer are compared with similar films having ALD Al2O3
      overlayers. 

PMID- 23978282
TI  - Reaction of 13-vertex carborane MU-1,2-(CH2)4-1,2-C2B11H11 with nucleophiles:
      linkage effect on product formation.
AB  - The length of C,C'-linkage has a great influence on the reactivity of 13-vertex
      carboranes. Reaction of 1,2-(CH2)4-1,2-C2B11H11 (1a) with Et2NH gave a 1:1 adduct
      nido-7-NEt2H-MU-1,3-(CH2)4-1,3-C2B11H11 (2). Compound 1a reacted with Me2NLi or
      Et2NLi to afford nido-[9-Nu-MU-7,8,10-(CH2)4CCH-B11H10](-) (Nu = NMe2, [3](-); Nu
      = NEt2, [4](-)). Complex [4](-) was also obtained by deprotonation of 2.
      Treatment of 1a with MeOH/base generated nido-[3-OMe-MU-1,2-(CH2)4-1,2-C2B11H11](
      ) ([5](-)) at room temperature, which was converted to nido-[MU-7,8
      (CH2)4CHB(OMe)2-7-CB10H11](-) ([6](-)) upon heating in the presence of Et3N.
      Complex [6](-) was oxidized by H2O2 to the corresponding alcohol [MU-7,8
      (CH2)4CHOH-7-CB10H11](-) ([7](-)) or hydrolyzed to the boronic acid [MU-7,8
      (CH2)4CHB(OH)2-7-CB10H11](-) ([8](-)). Reaction of 1a with (4-MeC6H4)SNa produced
      a CB11(-) anion closo-[MU-1,2-(CH2)4CHS(4-MeC6H4)-1-CB11H10](-) ([9](-)). The
      above complexes were fully characterized by (1)H, (13)C, and (11)B NMR
      spectroscopic data and elemental analyses. Molecular structures of 1-[7](-) and
      [9](-) were further confirmed by single-crystal X-ray analyses. 

PMID- 23978283
TI  - Rapid placement of bicaval dual-lumen catheter in a swine model of venovenous
      ECMO.
AB  - BACKGROUND: Venovenous (VV) extracorporeal membrane oxygenation (ECMO) applied
      through a single site with a bicaval dual-lumen (BCDL) catheter is a growing
      method of treatment of acute respiratory failure, thus animal models for research
      purposes are needed. We describe a rapid technique for the placement of the BCDL
      catheter for single-site VV ECMO in swine. DESIGN: Prior to the application of
      single-site VV ECMO model with common crossbred piglets, BCDL catheters were
      placed using anatomical landmarks. Transthoracic echocardiography (TTE) with
      color Doppler was used to determine catheter placement. Final determination of
      catheter placement was confirmed by necropsy. Arterial blood gas and hemodynamic
      parameters were recorded at baseline and then hourly. The values are mean +/- SD.
      RESULTS: Using anatomical landmarks by positioning the BCDL catheter tip
      approximately 6.5 cm distal to the tip of the manubrium, cannulation was easily
      accomplished in five piglets with no positional adjustments of the catheter
      required. Cannula placement was confirmed with both TTE color Doppler and
      necropsy. Respiratory support was achieved with baseline and hourly measurements
      of pH 7.45 +/- 0.03, 7.44 +/- 0.07, 7.46 +/- 0.05, 7.47 +/- 0.06 (p = NS); PO2 86
      +/- 30 mmHg, 98 +/- 30 mmHg, 94 +/- 40 mmHg, and 79 +/- 30 mmHg (p = NS); and
      PCO2 43 +/- 3 mmHg, 44 +/- 8 mmHg, 38 +/- 5 mmHg, and 40 +/- 4 mmHg (p = NS).
      CONCLUSIONS: Using anatomical landmarks for the placement of the BCDL catheter
      was rapid and effective in a swine model of VV ECMO, resulting in improved time
      efficiency for research.

PMID- 23978284
TI  - Dipotassium hydrogen phosphate as reducing agent for the efficient reduction of
      graphene oxide nanosheets.
AB  - By using dipotassium hydrogen phosphate (K2HPO4.3H2O), an efficient and
      environmentally friendly route for the reduction of the exfoliated graphene oxide
      nanosheets (GO) is reported in this work. The chemically reduced graphene oxide
      nanosheets (RGO) have been analyzed by X-ray diffraction, Fourier transform
      infrared spectroscopy, Raman spectra, X-ray photoelectron spectroscopy, Field
      emission transmission electron microscopy, Atomic force microscopy, and
      Thermogravimetric analysis. Considering the analysis results, dipotassium
      hydrogen phosphate plays a key role in the efficient removal of the oxygen
      containing groups in GO, which avoids the use of high toxic and hazardous
      reducing agents commonly used to obtain RGO in chemical reduction of GO.
      Dipotassium hydrogen phosphate itself and prepared graphene are environmentally
      friendly and inexpensive, which may open new opportunities for mass production of
      graphene by reducing GO.

PMID- 23978285
TI  - Visible light-induced surfactant-free emulsion polymerization using
      camphorquinone/tertiary amine as the initiating system for the synthesis of amine
      functionalized colloidal nanoparticles.
AB  - A visible light-induced surfactant-free emulsion polymerization (SFEP) was
      developed as an alternative pathway for the preparation of amine-functionalized
      nanoparticles by using the photo-initiating system consisting of camphorquinone
      coupled with tertiary amine (CQ/3 degrees -amine). Water-soluble macromolecules
      containing 3 degrees -amines were used as the sources of 3 degrees -amine
      species, which not only function with CQ to generate initiating free radicals,
      but also provide colloidal stabilization to the resulting colloidal products. The
      prepared nanoparticles showed uniformed size distribution and good colloidal
      stability with positively charged surface. For SFEP induced by
      CQ/polyethyleneimine (PEI) photo-redox couple, the polymerization of methyl
      methacrylate (MMA) was affected by both light intensity and initiator
      concentration. In addition, to obtain higher solid content products, the weight
      ratio of PEI:MMA=1:4 was employed. Finally, an opportunity for immobilizing
      various amine containing polymers by our photo-induced SFEP was evaluated. The
      achievement of this SFEP also depended on 3 degrees -amine content of the
      macromolecules used. 

PMID- 23978286
TI  - Periodic arrays of metal nanorings and nanocrescents fabricated by a scalable
      colloidal templating approach.
AB  - Here, we report a scalable bottom-up approach for fabricating periodic arrays of
      metal nanorings and nanocrescents. Wafer-scale monolayer silica colloidal
      crystals with an unusual non-close-packed structure prepared by a simple and
      rapid spin-coating technology are used as both etching and shadowing masks to
      create nanoring-shaped trenches in between templated polymer posts and
      sacrificial nanoholes. Directional deposition of metals in the trenches followed
      by liftoff of the polymer posts and the sacrificial nanoholes results in forming
      ordered metal nanorings. The inner and outer radii of the final nanorings are
      determined by the sizes of the templated polymer posts and the silica
      microspheres which can be easily adjusted by tuning the spin-coating and
      templating conditions. Most importantly, by simply controlling the tilt angle of
      the substrate toward the directional metal beams, continuous geometric transition
      from concentric nanorings to eccentric nanorings to nanocrescents can be
      achieved. This new colloidal templating approach is compatible with standard
      semiconductor microfabrication, promising for mass-production and on-chip
      integration of periodic nanorings and nanocrescents for a wide spectrum of
      technological applications ranging from nanooptical devices and ultrasensitive
      biosensing to magnetic memories and logic circuits. 

PMID- 23978287
TI  - Biomimetic mucin modified PLGA nanoparticles for enhanced blood compatibility.
AB  - Efforts to develop long circulating polymeric nanoparticles have propelled many
      strategies in nanoparticle surface modification to bypass immune surveillance and
      systemic clearance. In this context, our present study reports on the preparation
      and evaluation of mucin functionalized poly lactic-co-glycolic acid (PLGA)
      nanoparticles as hemocompatible, cell penetrating nanoparticulate drug delivery
      system. Amino groups of mucin were conjugated to the terminal carboxylic acid
      groups on PLGA to be followed by nanoparticle synthesis via standard solvent
      evaporation technique. Detailed in vitro experiments were performed to illustrate
      the significance of alternating copolymer structured mucin modified PLGA
      nanoparticles in terms of enhanced hemocompatibility and cellular uptake.
      Mucylation proved promising in controlling PLGA nanoparticle- interaction with
      plasma proteins (opsonins) and blood components via hemolysis, thrombogenecity
      and complement activation. Besides hemocompatibility, the modified and unmodified
      nanoparticles were also found to be cytocompatible with L929 and C6 cell lines.
      The fluorescent and confocal image analysis evaluated the extent of cellular
      uptake of nanoparticles into C6 cells. Specifically the combination of stealth
      properties and cellular internalization capacity of mucin modified PLGA
      nanoparticle (PLGA-Mucin) lead us to propose it as a safe, efficient and
      multifunctional nanoplatform for disease specific intravenous drug delivery
      applications as far as in vitro experiments are concerned. 

PMID- 23978288
TI  - Surface orientation of hydrophilic groups in sulfonated poly(ether ether ketone)
      membranes.
AB  - Sulfonated poly(ether ether ketone) copolymers (SPEEK) with a range of sulfonate
      contents (SC 77-51%) were synthesized via nucleophilic substitution
      polycondensation from hydroquinone and sulfonated hydroquinone. Membranes
      obtained by solvent casting from dimethylacetamide onto glass surfaces were
      analyzed for surface behavior. The surfaces of a membrane were hydrophobic in
      air, but hydrophilic in water. This surface behavior was corroborated by water
      contact angle vs. time, using sessile drop measurements. Hydrophilic sulfonic
      group aggregates on SPEEK chain and various media contacting with the top or
      bottom surfaces of the membrane during the fabrication process caused differences
      in surface behavior. Angle-dependent XPS showed that there was a higher atomic
      S/C ratio of the bottom surface than on the corresponding top surface. The
      hydrophilic sulfonic groups were in higher concentration within the membrane,
      with the concentration gradually decreasing towards the surface for SPEEK-HQ-80
      and SPEEK-HQ-70 membranes. Acidification with strong acid and higher temperature
      induced a more hydrophilic surface on a membrane than a milder acidification
      process. The depth profile at the membrane surface was examined by a combination
      of contact angle, XPS and ATR-FTIR. 

PMID- 23978289
TI  - Nanofibers-based nanoweb promise superhydrophobic polyaniline: from star-shaped
      to leaf-shaped structures.
AB  - Star-shaped and leaf-shaped polyaniline (PANI) hierarchical structures with
      interlaced nanofibers on the surface were successfully prepared by chemical
      polymerization of aniline in the presence of lithium triflate (LT). Chemical
      structure and composition of the star-like PANI obtained were characterized by
      FTIR and UV-vis spectra. PANI 2D architectures can be tailored from star-shaped
      to leaf-shaped structures by change the concentration of LT. The synthesized star
      like and leaf-like polyaniline show good superhydrophobicity with water contact
      angles of both above 150 degrees  due to the combination of the rough nanoweb
      structure and the low surface tension of fluorinated chain of dopant. This method
      is a facile and applicable strategy for a large-scale fabrication of 2D PANI
      micro/nanostructures. Many potential applications such as self-cleaning and
      antifouling coating can be expected based on the superhydrophobic PANI
      micro/nanostructures. 

PMID- 23978290
TI  - Gold nanoparticles paper as a SERS bio-diagnostic platform.
AB  - Bioactive papers are usually challenged by four major limitations: sensitivity,
      selectivity, simplicity and strength (4S). Gold nanoparticles (AuNPs) treated
      paper has previously been demonstrated as a Surface Enhanced Raman Scattering
      (SERS) active substrate, capable of addressing the 4S issues. In this study,
      AuNPs on paper substrate were functionalized by a series of biomolecules to
      develop a generic SERS platform for antibody-antigen detection. The
      functionalization steps were performed by taking advantage of the high affinity
      association between Streptomyces avidinii-derived protein, streptavidin, and
      biotin. Streptavidin was firstly bound onto the AuNPs treated paper using
      biotinylated-thiol. Subsequently, desired biotinylated-antibody was bound onto
      the streptavidin. SERS spectra of each functionalization step were obtained to
      ensure specific adsorption of the bio-molecules. The binding interaction of the
      antibody with its specific antigen was detected using SERS. Shifts of Raman band
      associated with alpha-helix and beta-sheet structures indicated structural
      modification of the antibody upon interaction with its antigen. Predominant
      tryptophan and tyrosine residue bands were also detected, confirming the presence
      of antigen. Reproducible spectral features were quantified as AuNP papers were
      subjected to different concentrations of antigen; the spectra intensity increased
      as a function of the antigen concentration. The retention of AuNPs on paper
      remained constant after all the consecutive washing and functionalization steps.
      The feasibility of AuNPs paper as a low-cost and generic SERS platform for bio
      diagnostic applications was demonstrated. 

PMID- 23978291
TI  - Organization of mixed dimethyldioctadecylammonium and choline modifiers on the
      surface of synthetic hectorite.
AB  - Understanding the nature of mixed surfactant self-assembly on the surface of
      organoclays is an important step toward optimizing their performance in polymer
      nanocomposites and for other potential applications, where selective surface
      interactions are crucial. In segmented thermoplastic polyurethane nanocomposite
      systems, dual-modified organoclays have shown significantly better performance
      compared to their single-modified counterparts. Until now, we had not fully
      characterized the physical chemistry of these dual-modified layered silicates,
      but had hypothesized that the enhanced composite performance arises due to some
      degree of nanoscale phase separation on the nanofiller surface, which enables
      enhanced compatibilization and more specific and inclusive interactions with the
      nanoscale hard and soft domains in these thermoplastic elastomers. This work
      examines the organization of quaternary alkyl ammonium compounds on the surface
      of Lucentite SWN using X-ray diffraction (XRD), thermogravimetric analysis (TGA),
      attenuated total reflectance Fourier-transfer infrared (ATR FT-IR), (13)C cross
      polarization (CP)/magic angle spinning (MAS) nuclear magnetic resonance (NMR),
      and small-angle neutron scattering (SANS). When used in combination with choline,
      dimethyldioctadecylammonium (DMDO) was observed to self-assemble into
      discontinuous hydrophobic domains. The inner part of these hydrophobic domains
      was essentially unaffected by the choline (CC); however, surfactant intermixing
      was observed either at the periphery or throughout the choline-rich phase
      surrounding those domains. 

PMID- 23978293
TI  - PSA testing without clinical indication for prostate cancer in relation to socio
      demographic and clinical characteristics in the Danish Diet, Cancer and Health
      Study.
AB  - BACKGROUND: Social differences in prostate cancer (PC) incidence and mortality
      might be related to testing for prostate-specific antigen (PSA). Although routine
      PSA screening is not recommended in Denmark, testing without clinical indication
      increased during the past decade. We evaluated associations between socio
      demographic or clinical characteristics and PSA testing without clinical
      indication. MATERIAL AND METHODS: In the Danish Diet, Cancer and Health Cohort,
      we identified 1051 men with PC diagnosed in 1993-2008. Diagnostic and clinical
      characteristics were obtained from medical records, and socio-demographic
      information was retrieved from administrative registers. We used general logistic
      regression analysis to estimate odds ratios (ORs) and 95% confidence intervals
      (CIs) for associations between socio-demographic or clinical characteristics and
      PSA testing without clinical indication. Cox regression analysis was used to
      examine associations with mortality. RESULTS: PSA testing without clinical
      indication was less likely among patients > 67 years (OR 0.7; 0.5-1.0). Men who
      were, PSA tested without clinical indication, were more likely to have vocational
      training (OR 1.8; 1.1-2.9) or higher education (OR 1.5; 0.9-2.5) and less likely
      to have advanced disease (OR 0.6; 0.4-0.9). PSA testing without clinical
      indication more often preceded therapy with curative intent (OR 1.8; 1.1-2.9) and
      less often palliative treatment (OR 0.6; 0.3-1.0). Men who were PSA tested
      without clinical indication had non-significantly lower overall and PC-specific
      mortality [hazard ratios 0.8 (0.5-1.2) and 0.6 (0.3-1.1), respectively].
      CONCLUSIONS: PSA testing without clinical indication was associated with higher
      educational level. PC detected by PSA testing with no clinical indication was
      more often localized and treated with curative intent.

PMID- 23978292
TI  - Nanotechnology approaches for inhalation treatment of fibrosis.
AB  - Cystic fibrosis (CF) is an autosomal recessive monogenetic disease that afflicts
      nearly 70,000 patients worldwide. The mutation results in the accumulation of
      viscous mucus in multiple organs especially in the lungs, liver and pancreas.
      High associated morbidity and mortality is caused by CF due to the lack of
      effective therapies. It is widely accepted that morbidity and mortality caused by
      CF is primarily due to the respiratory manifestations of the disease.
      Consequently, several approaches were recently developed for treatment of lung
      complications of CF. However, the lack of effective methods for delivery and
      especially targeted delivery of therapeutics specifically to lung tissues and
      cells limits the efficiency of the therapy. Local pulmonary delivery of
      therapeutics has two major advantages over systemic application. First, it
      enhances the accumulation of therapeutics specifically in the lungs and therefore
      increases the efficiency of the treatment. Second, local lung delivery
      substantially prevents the penetration of the delivered drug into the systemic
      circulation limiting adverse side effects of the treatment on other organs and
      tissues. This review is focused on different approaches to the treatment of
      respiratory manifestations of CF as well as on methods of pulmonary delivery of
      therapeutics.

PMID- 23978294
TI  - Normal-to-abnormal rearrangement and NHC activation in three-coordinate iron(II)
      carbene complexes.
AB  - The 'normal' three-coordinate iron-NHC complex [(IPr)Fe(N'')2] (N" = N(SiMe3)2)
      rearranges to its abnormal NHC analogue [(aIPr)Fe(N")2] (6) on heating, providing
      a rare abnormal iron-aNHC complex, and the first such three-coordinate complex.
      The tert-butyl-substituted complex [(I(t)Bu)Fe(N")2] (4) undergoes a thermal
      decomposition that has not previously been observed in iron-NHC chemistry,
      resulting in the bis(imidazole) complex [((t)BuIm)2Fe(N")2] (7). A mechanism that
      involves consecutive C-H and C-N activation is proposed to account for the
      formation of 7. 

PMID- 23978295
TI  - Have 2006 ATA practice guidelines affected the treatment of differentiated
      thyroid cancer in the United States?
AB  - BACKGROUND: There is wide variability in the degree of adherence to guideline
      recommendations among caregivers. Our aim was to determine the clinical impact of
      the 2006 guidelines from the American Thyroid Association (ATA) on the management
      of differentiated thyroid cancer (DTC) in the United States. METHODS: The
      Surveillance, Epidemiology and End Results (SEER) database (2004-2009) was
      employed. Patients were divided into two groups based on receipt of care before
      (DTC 04-06) and after (DTC 07-09) the release of the 2006 ATA guidelines.
      Adherence was determined with a chi-square test and binary logistic regression.
      Survival was analyzed with the Kaplan-Meier method and log-rank test. RESULTS: A
      total of 12,816 patients with DTC were identified between 2004 and 2006, and
      14,514 between 2007 and 2009 (DTC 07-09). Adherence to Recommendation 26
      (surgery) tended to increase in DTC 07-09 (82.2% vs. 83.2%, p=0.083). Factors
      associated with discordant practice among the DTC 07-09 group were older age,
      treatment in the Northeast, having more than one primary cancer, tumor size >4
      cm, and follicular and Hurthle cell histologies. Factors associated with
      accordance were treatment in the Midwest, level II-VI metastases, having lymph
      nodes examined, AJCC Stage III, and presenting with distant metastases. Patients
      treated in accordance with Recommendation 26 showed prolonged disease-specific
      survival (p<0.001). A trend toward more adherence to Recommendation 27
      (lymphadenectomy) was observed over time (68.4% vs. 69.7%, p=0.065). Adherence to
      Recommendation 27 was not associated with disease-specific survival (p=0.539).
      Less discordance from guidelines was seen for cancers that were 2.1-4 cm,
      extrathyroidal, and greater than Stage I. Overall accordance with Recommendation
      32 (radioactive iodine [RAI] ablation) increased in DTC 07-09 compared to DTC 04
      06 (61.7% vs. 57.5% respectively, p<0.001), and this was associated with improved
      disease-specific survival in DTC 07-09 (p<0.001). Predictors of care discordant
      with guidelines were patient age >= 65 years, living in the Northeast, and not
      undergoing total thyroidectomy. Factors associated with RAI use in accordance
      with guidelines were married status, treatment in the South, and having more than
      one lymph node examined. CONCLUSIONS: Care in accordance with evidence-based
      guidelines for DTC is associated with improved patient outcomes. Ongoing efforts
      should be undertaken to propagate guidelines to reduce variation in care and
      improve overall quality of care.

PMID- 23978297
TI  - The development of recipient-dependent sharing behavior and sharing expectations
      in preschool children.
AB  - This study investigated the development of sharing expectations and sharing
      behavior in 3 groups of 3-, 4-, and 5-year-old children. We examined (a) whether
      preschool children expect a person to share more with a friend than with a
      disliked peer and (b) whether their expectation about others' sharing behavior
      depends on whether there is a cost or not. Additionally, (c) we assessed
      children's own sharing behavior toward the different recipients in the same
      situation. The results show that expectations about sharing and actual sharing
      follow similar developmental pathways and that recipient-dependent sharing and
      sharing expectations emerge around 4 years of age. Moreover, individual-level
      analyses provide evidence that by 5 years of age, children's own sharing and
      their expectations of others' sharing are closely related to each other.

PMID- 23978296
TI  - Spontaneous belief attribution in younger siblings of children on the autism
      spectrum.
AB  - The recent development in the measurements of spontaneous mental state
      understanding, employing eye-movements instead of verbal responses, has opened
      new opportunities for understanding the developmental origin of "mind-reading"
      impairments frequently described in autism spectrum disorders (ASDs). Our main
      aim was to characterize the relationship between mental state understanding and
      the broader autism phenotype, early in childhood. An eye-tracker was used to
      capture anticipatory looking as a measure of false beliefs attribution in 3-year
      old children with a family history of autism (at-risk participants, n = 47) and
      controls (control participants, n = 39). Unlike controls, the at-risk group,
      independent of their clinical outcome (ASD, broader autism phenotype or typically
      developing), performed at chance. Performance was not related to children's
      verbal or general IQ, nor was it explained by children "missing out" on crucial
      information, as shown by an analysis of visual scanning during the task. We
      conclude that difficulties with using mental state understanding for action
      prediction may be an endophenotype of autism spectrum disorders.

PMID- 23978298
TI  - Social context effects in 2- and 4-year-olds' selective versus faithful
      imitation.
AB  - This study asked whether children's tendency to imitate selectively (ignore
      causally unnecessary actions) versus faithfully (overimitate causally unnecessary
      actions) varies across ages and social contexts. In the first experiment, 2-year
      olds and 4-year-olds were randomly assigned to play 1 of 3 prior games with a
      demonstrator: a mimicry game, an instrumental game, or a noninteractive control
      game. They then participated in a puzzle-box imitation task in which the
      demonstrator performed 1 causally necessary and 1 unnecessary action to retrieve
      an object. Whereas 4-year-olds imitated faithfully across all conditions, 2-year
      olds were more likely to imitate faithfully after a mimicry game and to imitate
      selectively after an instrumental game. Experiment 2 showed no effect of playing
      a mimicry game with a different experimenter prior to the imitation trials, thus
      ruling out 2-year-olds' faithful imitation being the result of motor priming or
      training effects. The results are discussed in terms of children's social
      affiliation and social-cognitive inferences.

PMID- 23978299
TI  - Gains and losses in creative personality as perceived by adults across the life
      span.
AB  - In this study, we used a life span model to study the subjective perception of
      creative personality (CP) in emerging, young, middle-aged, and older Hong Kong
      Chinese adults. We also asked participants to estimate the approximate age by
      which people develop and lose CP across adulthood. We expected an interesting
      interplay between internalized age stereotypes and age-related differentiation in
      beliefs about personality development. Older adults perceived increases in both
      gains and losses in CP in old age. But they still maintained a similar level of
      self-perceived CP traits when compared with young participants. Emerging, young,
      and middle-aged adults were less optimistic about their creativity development
      into old age. Young adults, in contrast to older adults, believed that gains in
      CP began and ceased at an earlier age. Positive perceptions of CP in one's aging
      process may have implications for aging successfully.

PMID- 23978301
TI  - Personality traits and living arrangements in young adulthood: selection and
      socialization.
AB  - Based on the social investment principle and theories of social relationship
      differentiation, the present study was conducted to investigate whether
      personality differences in high school predict young adults' living arrangements
      (with roommates or a romantic partner, alone, or staying with parents) 2 years
      later (selection) and whether these different social contexts provoke long-term
      personality changes (socialization). Using data from a 3-wave longitudinal study
      of 8,052 high school graduates in Germany, multinomial logistic regression
      analyses revealed substantial selection effects of the Big Five traits on living
      arrangements. Propensity score matching was applied to provide a strong test of
      the socialization effects of these living arrangements. Young adults who lived
      with roommates showed increases in Openness but the smallest increases in
      Conscientiousness. Living with a romantic partner was the most beneficial
      arrangement for the development of Conscientiousness. These results highlight the
      importance of social contexts for personality development in young adulthood.

PMID- 23978300
TI  - Personality-informed interventions for healthy aging: conclusions from a National
      Institute on Aging work group.
AB  - We describe 2 frameworks in which personality dimensions relevant to health, such
      as Conscientiousness, can be used to inform interventions designed to promote
      health aging. First, contemporary data and theory do not suggest that personality
      is "immutable," but instead focus on questions of who changes, in what way, why,
      when, and how. In fact, the notion that personality could be changed was part and
      parcel of many schools of psychotherapy, which suggested that long-term and
      meaningful change in symptoms could not be achieved without change in relevant
      aspects of personality. We review intervention research documenting change in
      personality. On the basis of an integrative view of personality as a complex
      system, we describe a bottom-up model of change in which interventions to change
      basic personality processes eventuate in changes at the trait level. A 2nd
      framework leverages the descriptive and predictive power of personality to tailor
      individual risk prediction and treatment, as well as refine public health
      programs, to the relevant dispositional characteristics of the target population.
      These methods dovetail with, and add a systematic and rigorous psychosocial
      dimension to, the personalized medicine and patient-centeredness movements in
      medicine. In addition to improving health through earlier intervention and
      increased fit between treatments and persons, cost-effectiveness improvements can
      be realized by more accurate resource allocation. Numerous examples from the
      personality, health, and aging literature on Conscientiousness and other traits
      are provided throughout, and we conclude with a series of recommendations for
      research in these emerging areas.

PMID- 23978302
TI  - Bidirectional associations between sleep (quality and duration) and psychosocial
      functioning across the university years.
AB  - Despite extensive research on sleep and psychosocial functioning, an important
      gap within the literature is the lack of inquiry into the direction of effects
      between these 2 constructs. The purpose of the present 3-year longitudinal study
      was to examine bidirectional associations between sleep (quality and duration)
      and 3 indices of psychosocial functioning (intrapersonal adjustment, friendship
      quality, and academic achievement). We also assessed the role of gender as a
      possible moderator of the patterns of results. Participants were 942 (71.5%
      female) emerging adults enrolled at a mid-sized university in southern Ontario,
      Canada, who ranged in age from 17 to 25 years (M = 19.01 years, SD = 0.90) at the
      first assessment. Students completed surveys in the winter term for 3 consecutive
      years, beginning in their first year of university. Survey measures included
      demographics, sleep quality and duration, intrapersonal adjustment (depressive
      symptoms, stress, and self-esteem), friendship quality, and academic achievement.
      Results of path analyses indicated a significant bidirectional association
      between sleep quality and intrapersonal adjustment. We also found evidence for
      unidirectional associations, such that better friendship quality and higher
      academic achievement predicted better sleep quality over time. Overall,
      psychosocial functioning was more strongly associated with sleep quality relative
      to sleep duration. Our findings highlight the importance of a longitudinal and
      holistic approach in understanding the link between sleep and psychosocial
      functioning among emerging adults at university.

PMID- 23978303
TI  - Candidate microRNA biomarkers in human epithelial ovarian cancer: systematic
      review profiling studies and experimental validation.
AB  - Despite advances in detection and therapy, epithelial ovarian cancer (EOC) still
      represents the most lethal gynecologic malignancy in women worldwide. The high
      mortality of EOC is mainly due to late-stage diagnosis for more than 70% of
      patients. There is an urgent need to search for specific and sensitive biomarkers
      for early diagnosis of EOC. Recently, the cumulative data indicated an essential
      role for microRNA (miRNA), a class of small non-coding RNAs targeting multiple
      mRNAs and triggering translation repression and/or RNA degradation, in ovarian
      caner carcinogenesis and progression. Here, we reviewed the published miRNA
      expression profiling studies that compared the miRNA expression profiles between
      EOC tissues or cell lines and normal ovarian tissues or benign ovarian tumor or
      human primary cultured ovarian surface epithelial cells. A miRNA ranking system
      that takes the number of comparisons in agreement and direction of differential
      expression into the consideration was devised and used. Finally, five promising
      differentially miRNAs (miR-200a, miR-100, miR-141, miR-200b, and miR-200c) were
      reported with the consistent direction in four or more studies. MiR-200a, miR
      200b, miR-200c, and miR-141, all of them belong to miR-200 family, were reported
      with consistently up-regulated in at least 4 studies, whereas miR-100 was
      reported with down-regulated in 4 studies. Furthermore, we validated these miRNAs
      in a clinical setting using qRT-PCR and their dysregulations in EOC tissues
      confirmed the findings. Conclusively, the five most consistently expressed miRNAs
      might provide some clues of the potential biomarkers in EOC. Further mechanistic
      and precise validation studies are needed for their clinical significances and
      roles in the progression of EOC. 

PMID- 23978305
TI  - An enhanced strip biosensor for rapid and sensitive detection of histone
      methylation.
AB  - Histone methylation is a crucial epigenetic modification of chromosomes. In this
      work, we describe an enhanced strip biosensor using oligonucleotide
      functionalized gold nanoparticles as an enhancer probe (AuNP-DNA) for rapid and
      sensitive detection of histone methylation. In conventional strip biosensor,
      methylated histone is captured on the test zone through the formation of
      antibody/methylated histone/antibody-labeled AuNP sandwich structures. Whereas,
      in the enhanced strip biosensor, the AuNPs in the sandwich structures are dual
      labeled with an antibody and another oligonucleotide (c-DNA). The sequence of the
      c-DNA is complementary to the oligonucleotide on the enhancer probe. The enhancer
      probe, AuNP-DNA, hybridizes with the c-DNA on the dual labeled AuNPs, and the
      color intensity of the red band on the test zone is then enhanced dramatically.
      The enhanced strip biosensor has been used for the visual detection of
      trimethylated lysine 9 of histone H3 (H3K9me3) in 20 ng of histone extract from
      HeLa cells within 15 min. The detection limit is 10-fold and 15-fold lower than
      the conventional strip biosensor and Western blot, respectively. 

PMID- 23978304
TI  - Matrix metalloproteinase-9 deletion is associated with decreased mid-term vein
      wall fibrosis in experimental stasis DVT.
AB  - INTRODUCTION: Post thrombotic syndrome therapy is primarily palliative, and the
      associated vein wall inflammatory mechanisms are unclear. Vein wall fibrotic
      injury following deep venous thrombosis (VT) is associated with elevated matrix
      metalloproteinases (MMPs). Whether and by what mechanism MMP9 directly
      contributes to vein wall remodeling after VT is unknown. METHODS: WT and MMP9 -/-
      mice underwent stasis VT by ligation of the inferior vena cava (IVC) and tissue
      was harvested at 2, 8, and 21days. Assessment of thrombus size, and gene, protein
      and structural vein wall determinations were done. RESULTS: VT resolution was
      increased in MMP9-/- mice as compared with controls at 21d only. The primary
      phenotypic fibrotic vein wall differences occurred at 8d post VT, with
      significantly less vein wall collagen content as assessed by Picosirius red
      staining in MMP9 -/- mice as compared with WT. Increased monocytic vein wall
      influx with less IL-1b and TGFb was found in MMP9 -/- vein walls as compared with
      WT. Corresponding levels of PAI-1 were increased in MMP9 -/- compared with WT,
      and no difference in FSP-1+cells as compared with controls. CONCLUSIONS: In
      stasis VT, MMP9 modulates midterm vein wall collagen content, with an altered
      local inflammatory and profibrotic environment, likely directed by monocytes.
      Thus, MMP9 plays a role in both vein wall responses as well as late thrombus
      resolution.

PMID- 23978306
TI  - Use of enoyl coenzyme A hydratase of Mycobacterium avium subsp. paratuberculosis
      for the serological diagnosis of Johne's disease.
AB  - Johne's disease (JD), caused by Mycobacterium avium subspecies paratuberculosis
      (MAP), remains difficult to control because of the lack of specific and sensitive
      diagnostic tests. In order to improve the specificity of sero-diagnosis for JD,
      the phage display library derived from genomic DNA of MAP was immunoscreened to
      identify novel antigenic targets. We selected a clone using antibodies from MAP
      experimentally infected cattle, and annotated its coding sequence as MAP1197 in
      the MAP genome, which encoded "echA12_2" in the MAP protein (Map-echA) belonging
      to Enoyl-CoA hydratase, known as a crotonase enzyme. The Map-echA was expressed
      in Esherichia coli and purified as a histidine-tag recombinant protein (rMap
      echA), and the diagnostic potential of the protein was further evaluated by
      enzyme-linked immunosorbent assays (ELISA). Antibody responses to rMap-echA were
      higher in MAP-infected cattle than in uninfected cattle. The specificity of the
      Map-echA ELISA was also confirmed by evaluation with hyper-immune sera against
      various kinds of Mycobacterium species. Furthermore, in all experimentally
      infected cattle the antibody against rMap-echA was detected 2-7months earlier
      than by a commercially available ELISA kit. These results suggested that Map-echA
      can be used as a specific and sensitive serological diagnostic antigen for the
      detection of MAP infection. 

PMID- 23978308
TI  - Methane C-H bond activation by "naked" alkali metal imidyl and alkaline earth
      metal imide complexes. The role of ligand spin and nucleophilicity.
AB  - High accuracy correlation consistent Composite Approach (ccCA) calculations have
      been used to investigate methane C-H bond activation with alkali metal imidyl and
      alkaline earth metal imide complexes. Alkali metals (Li, Na) and alkaline earth
      metals (Be, Mg) are used in this research given their redox innocence, namely,
      M(+) and M(2+), respectively. The ccCA calculations for methane activation by
      imidyl radical NH(*-) and triplet nitrene NH(**) show a thermodynamic
      (DeltaDeltaH = 13.2 kcal/mol) and kinetic (DeltaDeltaH(?) = 15.9 kcal/mol)
      preference for the former. Methane activation by LiNH(*) and MgNH proceeds via
      hydrogen atom abstraction (HAA) and [2 + 2] transition states; only HAA pathways
      are isolated for NaNH and BeNH. The ccCA computed enthalpies lead to the
      hypothesis that the nucleophilicity of the nitrogen of the activating ligand (NR)
      is the key ingredient in activating the strongest sp(3) C-H bonds like that of
      methane. 

PMID- 23978307
TI  - The equine alveolar macrophage: functional and phenotypic comparisons with
      peritoneal macrophages.
AB  - Alveolar macrophages (AMs) constitute the first line of defence in the lung of
      all species, playing a crucial role in the regulation of immune responses to
      inhaled pathogens. A detailed understanding of the function and phenotype of AMs
      is a necessary pre-requisite to both elucidating their role in preventing
      opportunistic bacterial colonisation of the lower respiratory tract and
      developing appropriate preventative strategies. The purpose of the study was to
      characterise this important innate immune cell at the tissue level by making
      functional and phenotypic comparisons with peritoneal macrophages (PMs). We
      hypothesised that the tissue of origin determines a unique phenotype of AMs,
      which may constitute an appropriate therapeutic target for certain equine
      respiratory diseases. Macrophages isolated from the lung and the peritoneal
      cavity of 9 horses were stimulated with various toll like receptor (TLR) ligands
      and the production of nitrite, tumour necrosis factor alpha (TNFalpha),
      interleukin (IL) 10 and indoleamine 2,3-dioxygenase (IDO) were measured by the
      Griess reaction and enzyme linked immunosorbent assay (ELISA) and/or quantitative
      polymerase chain reaction, respectively. Cells were also compared on the basis of
      phagocytic-capacity and the expression of several cell surface markers. AMs, but
      not PMs, demonstrated increased TNFalpha release following stimulation with LPS,
      polyinosinic polycytidylic acid (Poly IC) and heat-killed Salmonella typhinurium
      and increased TNFalpha and IDO mRNA expression when stimulated with LPS. AMs
      showed high expression of the specific macrophage markers cluster of
      differentiation (CD) 14, CD163 and TLR4, whereas PMs showed high expression of
      TLR4 only. AMs, but not PMs, demonstrated efficient phagocytic activity. Our
      results demonstrate that AMs are more active than PMs when stimulated with
      various pro-inflammatory ligands, thus supporting the importance of the local
      microenvironment in the activation status of the macrophage. This information
      provides a valuable knowledge base on which to improve our understanding of the
      role of macrophages and their microenvironment in equine innate immunity. 

PMID- 23978309
TI  - A validated stability-indicating TLC-densitometric method for the determination
      of stanozolol in pharmaceutical formulations.
AB  - BACKGROUND: Stanozolol is a synthetic derivative of dihydrotestosterone (DHT),
      and one of the frequently detected anabolic steroids in doping analysis. The
      current work describes the development and validation of the stability-indicating
      TLC-densitometric method for sensitive and specific estimation of stanozolol even
      its degradation product being there. Precoated silica gel TLC aluminium plates
      were utilized as the stationary phase and the eluent comprised of petroleum
      ether: acetone (6:4, v/v). Densitometric analysis of stanozolol was achieved at
      lambdamax 750 nm in the absorbance mode after staining with phosphomolybdic acid
      (PMA). Stress degradation of stanozolol was carried out under various reaction
      conditions including acid, base and neutral hydrolysis, wet and dry heating
      treatment, oxidation, and photo-degradation. Resulted stress samples and
      pharmaceutical products were analyzed with the developed TLC method. RESULTS:
      This system showed a compact spot for stanozolol at Rf value of 0.46 +/- 0.02.
      The data of linear regression analysis indicated a good linear relationship over
      the range of 200-1200 ng/spot concentrations. The method was validated for
      robustness, precision and recovery. The LOD and LOQ were 1.6 and 5.1 ng/spot,
      respectively. Under various stressed conditions, stanozolol showed degradation
      only under acidic hydrolysis. Peak of a degraded product was well resolved from
      the stanazolol with reasonably different Rf value and identified as 17, 17
      dimethyl-l8-nor-5alpha-androst-13(14)-eno [3,2c] pyrazole through 1D- and 2D-NMR
      spectroscopic techniques and ESI-QqTOF-MS/MS analysis. CONCLUSION: Result
      reflected that the stanozolol is majorly affected by the acidic condition.
      Statistical analysis indicated the application of the developed stability
      indicating TLC-densitometric method for routine analysis of stanozolol in the
      presence of its degradation product.

PMID- 23978311
TI  - The future of pharmacognosy in academic education.

PMID- 23978310
TI  - Effects of step length, age, and fall history on hip and knee kinetics and knee
      co-contraction during the maximum step length test.
AB  - BACKGROUND: Maximum step length is a brief clinical test involving stepping out
      and back as far as possible with the arms folded across the chest. This test has
      been shown to predict fall risk, but the biomechanics of this test are not fully
      understood. Knee and hip kinetics (moments and powers) are greater for longer
      steps and for younger subjects, but younger subjects also step farther. METHODS:
      To separate the effects of step length, age, and fall history on joint kinetics;
      healthy younger (age=27(5), N=14), older non-fallers (age=72(5), N=14), and older
      fallers (age=75(6), N=11) all stepped to the same relative target distances of 20
      80% of their height. Knee and hip kinetics and knee co-contraction were
      calculated. FINDINGS: Hip and knee kinetics and knee co-contraction all increased
      with step length, but older non-fallers and fallers utilized greater stepping hip
      and less stepping knee extensor kinetics. Fallers had greater stepping knee co
      contraction than non-fallers. Stance knee co-contraction of non-fallers was
      similar to young for shorter steps and similar to fallers for longer steps.
      INTERPRETATION: Age had minimal effects and fall history had no effects on joint
      kinetics of steps to similar distances. Effects of age and fall history on knee
      co-contraction may contribute to age-related kinetic differences and shorter
      maximal step lengths of older non-fallers and fallers, but step length correlated
      with every variable tested. Thus, declines in maximum step length could indicate
      declines in hip and knee extensor kinetics and impaired performance on similar
      tasks like recovering from a trip.

PMID- 23978312
TI  - Resolution of massive tophaceous gout with three urate-lowering drugs.

PMID- 23978313
TI  - Soluble reduced graphene oxide sheets grafted with polypyridylruthenium
      derivatized polystyrene brushes as light harvesting antenna for photovoltaic
      applications.
AB  - Soluble graphene nanosheets, prepared by grafting polystyrene-based polymer
      chains from the surface of reduced graphene oxide (RGO), have been functionalized
      with pendant Ru(II) polypyridine chromophores. N-Hydroxysuccinimide (NHS)
      derivatized p-vinylbenzoic acid polymer chains were grown from methyl
      bromoisobutyrate initiation sites on the surface of RGO by atom transfer radical
      polymerization (ATRP). Deprotection of the resulting NHS polystyrene chains
      followed by amide coupling with the amine-derivatized Ru(II) polypyridyl complex
      [Ru(4-CH2NH2-4'-CH3-bpy)(bpy)2](2+) (4-CH2NH2-4'-CH3-bpy = 4-aminomethyl-4'
      methyl 2,2'-bipyridine and bpy = 2,2'-bipyridine) afforded the covalently linked
      RGO-metallopolymer. The hybrid graphene-polymer assembly has been fully
      characterized with clear evidence for covalent attachment of the metallopolymer
      brushes to the graphene substrate. On the basis of thermal gravimetric analysis,
      one polymer strand is grafted to the surface of RGO for every hundred graphene
      carbons. The covalently linked polymer brushes feature controlled chain lengths
      of ~30 repeat units with a small polydispersity index (PDI, ~ 1.2). Photovoltaic
      cells based on the derivatized polymers and graphene-polymer assemblies were
      evaluated. The graphene-polymer assembly in the configuration, ITO/PEDOT:PSS/RGO
      PSRu/PC60BM/Al, exhibited enhanced photocurrent and power conversion efficiencies
      (~5 fold) relative to devices with the configuration,
      ITO/PEDOT:PSS/PSRu/PC60BM/Al. 

PMID- 23978314
TI  - Pharmacotherapies and harm-reduction options for the treatment of tobacco
      dependence.
AB  - INTRODUCTION: Tobacco dependence, a chronic relapsing condition, requires
      repeated interventions and multiple attempts to quit. AREAS COVERED: Strategies
      for assisting smoking cessation include behavioural counselling and
      pharmacotherapy. Three drugs are currently used as first-line pharmacotherapy:
      nicotine replacement therapy (NRT), bupropion and varenicline. Compared to
      placebo, the drug effect varies from RR = 2.27 for varenicline, to 1.69 for
      bupropion, and 1.60 for any form of NRT. Cytisine (similar to varenicline) has a
      RR = 3.98 compared to placebo (two trials). Second-line pharmacotherapies include
      nortriptyline and clonidine. This review also offers an overview of pipeline
      developments. EXPERT OPINION: Effective medications exist, and clinicians should
      encourage and offer treatment to every smoker. However, most smokers try to quit
      by themselves, with only about 3% quitting successfully each year. Alternative
      interventions are needed. Harm reduction has not received much support to date.
      Safer alternative to tobacco smoking (smoke-free products, long-term use of
      cessation drugs, or electronic cigarettes) could save lives and reduce the burden
      of tobacco-related deaths and diseases. Despite some encouragement to develop a
      research agenda for e-cigarettes, particularly on the safety issues, too little
      attention has been brought to this area of research.

PMID- 23978315
TI  - Comment on purification and characterization of chromium-binding substances from
      high-chromium yeast.

PMID- 23978317
TI  - Quantification of human kallikrein-2 in clinical samples by selected reaction
      monitoring.
AB  - Recently, the number of mass spectrometry-based quantification assays has been
      increased, partially due to the global efforts of chromosome-centric human
      proteome project (C-HPP). Our goal at the Chromosome 19 Consortium is to provide
      novel selected reaction monitoring (SRM) assays of proteins coded on chromosome
      19. We have selected the two most useful signature peptides (NSQVWLGR and
      HNLFEPEDTGQR) of human kallikrein-2 (hK2 - NX_P20151) and developed an SRM assay.
      Details of the analytical parameters, including multiple transitions by peptides,
      are presented. The endogenous levels of hK2 were determined in clinical samples
      (n = 35). The limit of quantification was also estimated by spiking heavy isotope
      labeled peptides into seminal plasma samples at various concentrations (LOQ ~ 29
      ng/mL). 

PMID- 23978316
TI  - Prevalence of measles antibodies among health care workers in Catalonia (Spain)
      in the elimination era.
AB  - BACKGROUND: Interruption of measles transmission was achieved in Catalonia
      (Spain) in 2000. Six years later, a measles outbreak occurred between August 2006
      and June 2007 with 381 cases, 11 of whom were health care workers (HCW).The
      objective was to estimate susceptibility to measles in HCW and related
      demographic and occupational characteristics. METHODS: A measles seroprevalence
      study was carried out in 639 HCW from six public tertiary hospitals and five
      primary healthcare areas. Antibodies were tested using the Vircell Measles ELISA
      IgG Kit. Data were analyzed according to age, sex, type of HCW, type of centre
      and vaccination history.The odds ratios (OR) and their 95% CI were calculated to
      determine the variables associated with antibody prevalence. OR were adjusted
      using logistic regression.Positive predictive values (PPV) and the 95% confidence
      intervals (CI) of having two documented doses of a measles containing vaccine
      (MCV) for the presence of measles antibodies and of reporting a history of
      measles infection were calculated. RESULTS: The prevalence of measles antibodies
      in HCW was 98% (95% CI 96.6-98.9), and was lower in HCW born in 1981 or later,
      after the introduction of systematic paediatric vaccination (94.4%; 95% CI 86.4
      98.5) and higher in HCW born between 1965 and 1980 (99.0%; 95% CI 97.0-99.8).
      Significant differences were found for HCW born in 1965-1980 with respect to
      those born in 1981 and after (adjusted OR of 5.67; 95% CI: 1.24-25.91).A total of
      187 HCW reported being vaccinated: the proportion of vaccinated HCW decreased
      with age. Of HCW who reported being vaccinated, vaccination was confirmed by the
      vaccination card in 49%. Vaccination with 2 doses was documented in only 50 HCW,
      of whom 48 had measles antibodies. 311 HCW reported a history of measles.The PPV
      of having received two documented doses of MCV was 96% (95% CI 86.3-99.5) and the
      PPV of reporting a history of measles was 98.7% (95% CI 96.7-99.6). CONCLUSIONS:
      Screening to detect HCW who lack presumptive evidence of immunity and vaccination
      with two doses of vaccine should be reinforced, especially in young workers, to
      minimize the risk of contracting measles and infecting the susceptible patients
      they care for.

PMID- 23978318
TI  - Nanometallic glasses: size reduction brings ductility, surface state drives its
      extent.
AB  - We report tensile experiments on Ni80P20 metallic glass samples fabricated via a
      templated electroplating process and via focused ion beam milling, which differed
      only in their surface energy states: Ga-ion-irradiated and as-electroplated.
      Molecular dynamics simulations on similar Ni80Al20 systems corroborate the
      experimental results, which suggest that the transition from brittle to ductile
      behavior is driven by sample size, while the extent of ductility is driven by
      surface state. 

PMID- 23978319
TI  - Co-existence of mutations in the FBN1 gene and the ABCC6 gene in a patient with
      Marfan syndrome associated with pseudoxanthoma elasticum.

PMID- 23978321
TI  - An updated and expanded meta-analysis of nonresident fathering and child well
      being.
AB  - Since Amato and Gilbreth's (1999) meta-analysis of nonresident father involvement
      and child well-being, nonmarital childbirths and nonresident father involvement
      both have increased. The unknown implications of such changes motivated the
      present study, a meta-analytic review of 52 studies of nonresident father
      involvement and child well-being. Consistent with Amato and Gilbreth, we found
      that positive forms of involvement were associated with benefits for children,
      with a small but statistically significant effect size. Amounts of father-child
      contact and financial provision, however, were not associated with child well
      being. Going beyond Amato and Gilbreth, we analyzed the associations between
      different types of fathering and overall child well-being, and between overall
      father involvement and different types of child well-being. We found that
      nonresident father involvement was most strongly associated with children's
      social well-being and also was associated with children's emotional well-being,
      academic achievement, and behavioral adjustment. The forms of father involvement
      most strongly associated with child well-being were involvement in child-related
      activities, having positive father-child relationships, and engaging in multiple
      forms of involvement. Moderator analyses demonstrated variation in effect sizes
      based on both study characteristics and demographic variables. We discuss the
      implications of these findings for policy and practice.

PMID- 23978320
TI  - Synchrony of diurnal cortisol pattern in couples.
AB  - Cortisol is a biomarker of stress reactivity, and its diurnal pattern is an
      indicator of general neuroendocrine health. Despite theories conceptualizing
      marital dyads as dynamic systems wherein spouses are interdependent in their
      physiology and stress coping, little is known about the daily processes in which
      spouses possibly influence each other in biological stress. Nineteen heterosexual
      couples provided saliva samples containing cortisol 4 times a day for 4
      consecutive days. We used multilevel modeling to examine whether one's cortisol
      awaking response (CAR) and diurnal cortisol slope (DCS) predict those of the
      spouse's on the same day and/or on the next day. We found that spouses
      synchronize their DCS, such that on days when one experiences faster or slower
      decline in diurnal cortisol than usual, the spouse also experiences faster or
      slower decline than usual. For CAR, positive synchrony was only observed in
      couples reporting high levels of marital strain and disagreement. Cross-lagged
      regression analysis reveals stability in diurnal cortisol pattern. A steeper
      cortisol slope on a particular day predicts a steeper slope on the next day
      within an individual, but no significant cross-lagged relation was found between
      spouses. Couples reporting more spousal support tend to have stronger stability
      in CAR. These findings provide evidence that spouses are interdependent in their
      diurnal cortisol patterns on a day-to-day basis, and that these daily dynamics
      are associated with marital relationship quality. The study contributes to our
      understanding of marital processes and biobehavioral health. It also contributes
      methodologically to the advancement of longitudinal dyadic analysis.

PMID- 23978322
TI  - Motherhood, reasons for living, and suicidality among African American women.
AB  - This report examines the protective role of motherhood against suicidal ideation
      among low-income African American women with a history of suicide attempts.
      Findings from previous studies examining the relations between family factors and
      suicide risks are inconsistent in this population, indicating that family could
      both exacerbate and reduce risks. Research on the link between motherhood-status
      specifically and suicide risk is rare, but family and child-related concerns have
      been identified as unique reasons for living associated with reduced risk of
      suicide attempt. Self-identified African American women (N = 146), ages 18-64,
      who attempted suicide within the previous 12 months were recruited from a large
      urban public hospital. A bootstrapping mediation model was tested using
      motherhood status from the demographics measure as the predictor, the Reasons for
      Living (RFL) scales as the mediator, and the Beck Suicidal Ideation Scale as the
      outcome. The model accounted for 41% of the variance in suicidal ideation and the
      indirect effect of RFL was statistically significant. These findings provide
      empirical support for the hypothesis that motherhood is protective against
      suicidal ideation among African American women with a history of suicide
      attempts. Future research should seek to determine how incorporating the
      protective function of motherhood status in clinical interventions with this high
      risk population might help to improve treatment effectiveness.

PMID- 23978323
TI  - Effectiveness of preventive family intervention in improving cognitive
      attributions among children of depressed parents: a randomized study.
AB  - Our randomized trial examined the effectiveness of preventive interventions in
      increasing positive cognitive attributions and reducing negative cognitive
      attributions in children of depressed parents. In addition, it tested the role of
      attribution changes in mediating the intervention effects on children's
      depressive and emotional symptoms. The participants were 109 Finnish families
      with at least one parent in treatment for affective disorder, for a total of 145
      children, 8-16 years of age. Families were randomized into two groups: the
      "family talk intervention" (FTI, a whole-family approach enhancing communication
      and child resilience, Beardslee et al., 1997) group, and an active control, the
      "let's talk about the children" (LTC, a parent-only psycho-educational approach,
      Solantaus, Paavonen, Toikka, & Punamaki, 2010) group. Children reported their
      cognitive attributions (CASQ-R, Children's Attributional Style Questionnaire
      Revised (Thompson, Kaslow, Weiss, & Nolen-Hoeksema, 1998)), depressive (CDI/BDI,
      Child Depression Inventory (Kovacs, 1981)/Beck Depression Inventory (Beck, Steer,
      & Garbin, 1988)) and emotional (SDQ, Strengths and Difficulties Questionnaire
      (Goodman, 1997)) symptoms, and mothers reported their children's emotional
      symptoms (SDQ at baseline (T1) and 10-month (T2) and 18-month (T3)) follow-ups.
      Contrary to our hypothesis, no beneficial attribution changes were found in the
      FTI group across the follow-ups. Instead, positive cognitive appraisals increased
      in the LTC group, especially from T2 to T3. The increase of positive attribution
      further served as a mediator for changes in children's emotional and depressive
      symptoms. The findings suggest that a short preventive intervention can enhance
      beneficial cognitive processes in high-risk families in routine adult psychiatric
      care.

PMID- 23978325
TI  - High apolipoprotein E in cerebrospinal fluid of patients with Lewy body disorders
      is associated with dementia.
AB  - Apolipoprotein E epsilon4 allele (APOE epsilon4) increases the apolipoprotein E
      (apoE) protein levels in Alzheimer's disease (AD) cerebrospinal fluid (CSF).
      Thus, we hypothesized that apoE levels were also associated with the APOE
      genotype, and amyloid-beta (Abeta)-associated clinical, functional, and imaging
      parameters in patients with Lewy body-associated disorders (LBD). Indeed, similar
      to AD, patients with LBD displayed high CSF apoE levels (greatest in patients
      with dementia with LBD), and this was linked to APOE epsilon4. High CSF apoE
      protein correlated positively with CSF soluble amyloid precursor protein, total
      tau, and cortical and striatal Pittsburgh compound B retention; and correlated
      negatively with CSF Abeta42, cognitive tests scores, and glucose uptake ratio in
      the temporal and parietal cortices. APOE epsilon4-triggered accumulation of apoE
      in CSF is related to Abeta-associated clinical and functional imaging parameters
      in LBD. Accordingly, therapeutic strategies aimed at reducing apoE levels in the
      brain should be explored not only in AD but also in LBD, particularly when
      accompanied with dementia. 

PMID- 23978324
TI  - A platform for discovery: The University of Pennsylvania Integrated
      Neurodegenerative Disease Biobank.
AB  - Neurodegenerative diseases (NDs) are defined by the accumulation of abnormal
      protein deposits in the central nervous system (CNS), and only neuropathological
      examination enables a definitive diagnosis. Brain banks and their associated
      scientific programs have shaped the actual knowledge of NDs, identifying and
      characterizing the CNS deposits that define new diseases, formulating staging
      schemes, and establishing correlations between neuropathological changes and
      clinical features. However, brain banks have evolved to accommodate the banking
      of biofluids as well as DNA and RNA samples. Moreover, the value of biobanks is
      greatly enhanced if they link all the multidimensional clinical and laboratory
      information of each case, which is accomplished, optimally, using systematic and
      standardized operating procedures, and in the framework of multidisciplinary
      teams with the support of a flexible and user-friendly database system that
      facilitates the sharing of information of all the teams in the network. We
      describe a biobanking system that is a platform for discovery research at the
      Center for Neurodegenerative Disease Research at the University of Pennsylvania.

PMID- 23978326
TI  - Gait analysis of anterior cruciate ligament reconstructed subjects with a
      combined tendon obtained from hamstring and peroneus longus.
AB  - BACKGROUND: Stability of the knee joint is achieved by a complex process in which
      the anterior cruciate ligament (ACL) plays an important role. The rupture of this
      ligament is quite frequent especially in athletic young subjects. Various methods
      have been used to reconstruct the ACL. One of the new methods is to use a graft
      combined from peroneus longus and hamstring. As there is no evidence regarding
      this method, it was aimed to evaluate the efficiency of this method. METHOD: Two
      groups of normal and those with ACL injury, in whom their ACLs were reconstructed
      with the new method, participated in this study. The kinematic and kinetic
      parameters during walking on level surface were evaluated by a motion analysis
      system (Qualysis) and a Kistler force plate. The difference between the
      parameters of operated and non-operated sides and also between patients and
      normal subjects was evaluated by use of a two sample t test (p-value was 0.05).
      RESULTS: The results of this study showed that the pattern and magnitude of the
      loads transmitted by lower extrimity joints differed between normal and ACL
      reconstructed subjects. The sound side pattern and magnitude of motion were also
      influenced by ACL insufficiency. CONCLUSIONS: The results of the current study
      showed that the reconstructed ACL by use of this method did not have enough
      performance to restore the function of the leg. As the knee joint is unstable
      following the use of this method, it is recommended to find a new method of ACL
      reconstruction to improve the function of this ligament after reconstruction.

PMID- 23978328
TI  - Prevalence and factors associated with frailty among Peruvian older adults.
AB  - The objective of this study is to examine the prevalence and factors associated
      with frailty in Peruvian Navy Veteran's older adults and family members. A total
      of 311 non-institutionalized men and women aged 60 years and older, from the
      Geriatrics Service of the Peruvian Navy Medical Center (Centro Medico Naval
      "Cirujano Mayor Santiago Tavara") were assessed between May and October 2010.
      Frailty was defined as having two or more of the following components: (1)
      unintentional weight-loss, (2) weakness (lowest 20% in grip-strength), (3) self
      reported exhaustion, and (4) slow walking speed (lowest 20% 8-m walk-time in
      seconds). Additionally, information on socio-demographic factors, medical
      conditions, depressive symptoms, disability, and cognitive function were
      obtained. Of the 311 participants, 78 (25.1%) were not frail, 147 (47.3%) were
      pre-frail, and 86 (27.8%) were frail. Using logistic regression analysis, we
      found that older age, being married, falls in the last year and disability were
      factors significantly associated with being frail. We conclude that prevalence of
      pre-frail and frail status in Peruvian Navy Veterans and family members is high.
      Our data reports risk factors for frailty that have been reported in the past in
      other population groups. A larger sample and longitudinal follow-up are needed to
      design and implement comprehensive geriatric interventions that can benefit
      Peruvian Navy Veteran's older adults at risk of becoming frail. 

PMID- 23978327
TI  - Influenza virus hemagglutinin stalk-based antibodies and vaccines.
AB  - Antibodies against the conserved stalk domain of the hemagglutinin are currently
      being discussed as promising therapeutic tools against influenza virus
      infections. Because of the conservation of the stalk domain these antibodies are
      able to broadly neutralize a wide spectrum of influenza virus strains and
      subtypes. Broadly protective vaccine candidates based on the epitopes of these
      antibodies, for example, chimeric and headless hemagglutinin structures, are
      currently under development and show promising results in animals models. These
      candidates could be developed into universal influenza virus vaccines that
      protect from infection with drifted seasonal as well as novel pandemic influenza
      virus strains therefore obviating the need for annual vaccination, and enhancing
      our pandemic preparedness. 

PMID- 23978330
TI  - Modulation of c-kit expression in pancreatic adenocarcinoma: a novel stem cell
      marker responsible for the progression of the disease.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because
      of late symptoms and resistance to chemotherapy and radiation therapy. We have
      investigated the appearance of c-kit, a stem cell marker, in both normal adult
      pancreatic tissue and in cancerous tissue. Apart from some very pale staining of
      islets of Langerhans, normal pancreas was devoid of staining with antibodies to c
      kit. In contrast, in cancerous tissue that still preserves the overall integrity
      of the pancreatic tissue, there was a clear labeling in islets of Langerhans,
      which seemed to be co-localized with insulin containing beta cells. In other
      cases, where the pancreatic tissue was completely deteriorated, intensive
      labeling was clearly evident in remnants of both the exocrine and the endocrine
      tissues. The duct cells of the adenocarcinoma were moderately but clearly labeled
      with antibodies to c-kit. In contrast, in metastasis of PDAC, very intensive
      labeling of c-kit was evident. The location of KRAS, which is strongly associated
      with PDAC, was also analyzed at the initial stages of the disease, when islets of
      Langerhans still preserve their integrity to a large extent. KRAS was found
      exclusively in islets of Langerhans and overlapped in its location with insulin
      and c-kit expressing cells. It is suggested that the modulation of the expression
      of c-kit, visualized by antibodies to the oncogene molecule, may play an
      important role in the formation and progression of PDAC. The absence of c-kit in
      normal pancreas and its appearance in PDAC is probably due to a mutational event,
      which probably allows conversion of the beta cells into cancer stem cells (CSC).
      Co-expression of both c-kit and KRAS, typical markers for CSC with overlapping
      with insulin in islets of Langerhans, strongly support the notion that beta-cells
      play a central role in the development of PDAC. The use of specific drugs that
      can attenuate the kinase activity of c-kit or target KRAS expressing cancer cells
      should be tested in order to attenuate the progression of this lethal disease. 

PMID- 23978329
TI  - Gender-specific associations between functional autonomy and physical capacities
      in independent older adults: results from the NuAge study.
AB  - BACKGROUND: Even with healthy and active aging, many older adults will experience
      a decrease in physical capacities. This decrease might be associated with
      diminished functional autonomy. However, little is known about the physical
      capacities associated with functional autonomy in older women and men. OBJECTIVE:
      This study aimed to examine gender-specific associations between functional
      autonomy and physical capacities in independent older women and men. METHODS:
      Secondary analyses were carried out using cross-sectional data from 652 women and
      613 men who participated in the NuAge longitudinal study. The "functional
      autonomy measurement system" (SMAF) was used to evaluate functional autonomy. The
      physical capacities measured (tests used) were: biceps and quadriceps strength
      (Microfet dynamometer), grip strength (Martin vigorimeter), unipodal balance,
      changing position & walking (timed up and go), normal & fast walking (four-meter
      walking speed) and changing position (chair stand). Correlation and multiple
      linear regression analyses adjusted for age, depressive symptoms and body
      composition were performed. RESULTS: On average, participants were aged 73 years
      and had mild to moderate functional autonomy loss. In women, after controlling
      for age, depressive symptoms and body composition, greater functional autonomy
      was best explained by faster changing position & walking skills and superior
      biceps strength (R(2)=0.46; p<0.001). After controlling for depressive symptoms,
      faster changing position & walking skills and better unipodal balance best
      explained greater functional autonomy in men (R(2)=0.21; p<0.001). CONCLUSION:
      According to these results, physical capacities are moderately associated with
      functional autonomy among independent older adults, especially women.

PMID- 23978331
TI  - Electrochemical determination of heme-linked pKa values and the importance of
      using fluoride binding in heme proteins.
AB  - The ultraviolet-visible (UV-vis) spectroelectrochemical measurements of heme
      proteins in the presence of a heme-bound fluoride ion can be used as a probe for
      heme-linked ionizations of acid-base groups in the heme pocket. A detailed study
      of the pH dependence of the midpoint potential of skeletal horse myoglobin (Mb)
      with a heme-bound fluoride ion (Mb-F) reveals how protonation of the distal
      histidine (H64) changes the redox properties of the protein with a determined pKa
      of 5.3. In addition, fluoride binding in myoglobin provides a stabilization of 
      1.9 kcal/mol of the ferric Mb-F relative to ferric Mb without fluoride.

PMID- 23978332
TI  - Perfluorooctanoate suppresses spheroid attachment on endometrial epithelial cells
      through peroxisome proliferator-activated receptor alpha and down-regulation of
      Wnt signaling.
AB  - Exposure of animals to perfluorooctanoic acid (PFOA), a surfactant used in
      emulsion polymerization processes causes early pregnancy loss, delayed growth and
      development of fetuses. The mechanisms of action are largely unknown. We studied
      the effect of PFOA on implantation using an in vitro spheroid-endometrial cell co
      culture model. PFOA (10-100MUM) significantly reduced Jeg-3 spheroid attachment
      on RL95-2 endometrial cells. PFOA also suppressed beta-catenin expression in Jeg
      3 cells. The Wnt agonist Wnt3a stimulated beta-catenin expression in Jeg-3 cells
      and reversed the PFOA suppression of the spheroid attachment. The putative PFOA
      receptors (PPARalpha, beta, gamma) present in both cell lines were not affected
      by PFOA (0.01-100MUM). The PPARalpha antagonist MK886 restored the beta-catenin
      and E-cadherin expression levels in Jeg-3 cells and reversed the suppression of
      the spheroid attachment caused by PFOA. Taken together, PFOA suppresses spheroid
      attachment through PPARalpha and Wnt signaling pathways via down-regulation of
      beta-catenin and E-cadherin expression. 

PMID- 23978333
TI  - Possible involvement of oxidative stress as a causative factor in blood-brain
      barrier dysfunction in stroke-prone spontaneously hypertensive rats.
AB  - To elucidate the pathogenic roles of oxidative stress on blood-brain-barrier
      (BBB) dysfunction, we compared the chronological changes of oxidative stress in
      blood and cerebral tissue between stroke-prone spontaneously hypertensive rats
      (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Plasma and tissue oxidative
      stress was assayed by the diacron-reactive oxygen metabolite (d-ROM) test using 8
      hydroxy-2'-deoxyguanosine (8-OHdG) as a reference oxidative stress marker. The
      plasma and cerebral cortex d-ROM levels increased in SHRSP after 16weeks of age,
      but not in WKY. There were no significant differences in 8-OHdG or lipid
      peroxidation markers between SHRSP and WKY. Antioxidant capacity, as estimated by
      the biological antioxidant potential test, was similar between SHRSP and WKY at
      all ages examined. The changes in plasma and tissue d-ROM levels coincided with
      changes in glucose transporter-1 and aquaporin-4 expression, as functional
      constituents of the BBB. These results indicate that plasma oxidative stress
      increases before the onset of tissue damage, and plays an important role in BBB
      dysfunction rather than decreases in antioxidant capacity. The plasma d-ROM test
      appears to be useful for predicting vasogenic cerebral edema in severe
      hypertension. 

PMID- 23978334
TI  - A simple method for isolating and culturing the rat brain microvascular
      endothelial cells.
AB  - Brain microvascular endothelial cells (BMECs), a main component of the blood
      brain barrier, play a critical role in the pathogenesis of many brain diseases.
      The primary culture of BMECs has been used in various models for studying
      cerebrovascular diseases in vitro. However, there are still several problems
      existing in the isolation and cultivation of primary rat BMECs, such as low
      yield, contamination with other cell types, and requirement of a large number of
      animals and expensive growth factor. In this study, we describe a simple,
      economical (without any growth factor) and repeatable method to obtain
      endothelial cells with high purity (>99%) and yield (about 2.2*10(7) per rat)
      from cerebral cortexes of neonatal rat, mainly from gray matter. In vitro
      examinations determined that the isolated cells expressed typical phenotypic
      markers of differentiated brain endothelium such as multiple drug resistant
      protein, von Willebrand factor, platelet endothelial cell adhesion molecule 1
      (PECAM-1/CD31), and intercellular adhesion molecule (ICAM). These cells also
      possessed morphological and ultra-structural characteristics that were observed
      by phase contrast microscope and electric microscope. Then GFAP and alpha-SMA
      were used, respectively, to identify astrocyte and pericyte which were potential
      to contaminate primary culturing of BMECs. And specific reaction of endothelial
      cells to external stimulation was tested by culture with TNF-alpha for 24h. All
      these results of our experiments supply that our protocol provides an effective
      and reliable method to obtain high purity and yield of rat BMECs and offers a
      useful tool for studying cellular physiology, cerebrovascular diseases, brain
      tumors, blood-brain barrier and neurovascular units, etc. 

PMID- 23978335
TI  - FGF-1 delivery from multilayer alginate microbeads stimulates a rapid and
      persistent increase in vascular density.
AB  - In recent years, great advances have been made in the use of islet
      transplantation as a treatment for type I diabetes. Indeed, it is possible that
      stimulation of local neovascularization upon transplantation could improve
      functional graft outcomes. In the present study, we investigate the use of
      multilayered alginate microbeads to provide a sustained delivery of FGF-1, and
      whether this results in increased neovascularization in vivo. Multilayered
      alginate microbeads, loaded with either 150ng or 600ng of FGF-1 in the outer
      layer, were surgically implanted into rats using an omentum pouch model and
      compared to empty microbead implants. Rats were sacrificed at 4days, 1week, and
      6weeks. Staining for CD31 showed that both conditions of FGF-1 loaded microbeads
      resulted in a significantly higher vessel density at all time points studied.
      Moreover, at 6weeks, alginate microbeads containing 600ng FGF-1 provided a
      greater vascular density compared to both the control group and the microbeads
      loaded with 150ng FGF-1. Omenta analyzed via staining for smooth muscle alpha
      actin showed no variation in mural cell density at either 4days or 1week. At
      6weeks, however, omenta exposed to microbeads loaded with 600ng FGF-1 showed an
      increase in mural cell staining compared to controls. These results suggest that
      the sustained delivery of FGF-1 from multilayered alginate microbeads results in
      a rapid and persistent vascular response. An increase in the local blood supply
      could reduce the number of islets required for transplantation in order to
      achieve clinical efficacy. 

PMID- 23978336
TI  - Timing of arteriovenous fistula creation in patients With CKD: a decision
      analysis.
AB  - BACKGROUND: The optimal time for arteriovenous fistula (AVF) referral is
      uncertain. Improving the timeliness of referral may reduce central venous
      catheter (CVC) use. STUDY DESIGN: Monte Carlo simulation model. SETTING &
      POPULATION: Patients with chronic kidney disease (CKD) followed up in a
      multidisciplinary clinic, overall and stratified by age. MODEL, PERSPECTIVE, &
      TIMEFRAME: Decision analysis, patient, patient's lifetime. INTERVENTION: AVF
      referral, using 1 of 2 strategies: refer when hemodialysis is anticipated to
      begin within a certain time frame or refer when estimated glomerular filtration
      rate (eGFR) drops below a certain threshold. OUTCOMES: A range of values for each
      strategy are compared to each other with respect to incident vascular access type
      (AVF or CVC), percentage of patients with an unnecessary AVF creation, and life
      expectancy after dialysis therapy initiation. RESULTS: A 15-month referral time
      frame gave 34% with incident CVCs, 14% with unnecessary AVFs, and a life
      expectancy of 1,751 days. Time frames of 12-18 months performed similarly.
      Referral at eGFR of 20 mL/min/1.73 m(2) gave 38% with incident CVCs, 20% with
      unnecessary AVFs, and life expectancy of 1,742 days. Using an eGFR threshold of
      15 mL/min/1.73 m(2), 10% had an unnecessary AVF. Policy performance was affected
      by CKD progression rate and age. For fast progressors (DeltaeGFR = -7mL/min/1.73
      m(2) per year), referral at eGFR of 25 mL/min/1.73 m(2) achieved a similar
      incident CVC percentage (~40%) as referral at 15 mL/min/1.73 m(2) in slower
      progressors (DeltaeGFR = -2.78 mL/min/1.73 m(2) per year). For patients aged 70
      80 and 80-90 years, time frames of 15-18 months yielded 16%-22% with unnecessary
      AVFs (vs 9%-11% in 50- to 60-year-olds); an eGFR threshold strategy of 20
      mL/min/1.73 m(2) yielded 24% unnecessary AVFs in 80- to 90-year-olds versus 16%
      in 50- to 60-year-olds. LIMITATIONS: Our model does not consider patients with
      nonlinear CKD progression or acute kidney injury. We did not include
      arteriovenous grafts or consider cost or quality of life. CONCLUSIONS: In
      general, AVF referral within about 12 months of the estimated time to dialysis
      performed best among time frame strategies, and referral at eGFR < 15-20
      mL/min/1.73 m(2) performed best among threshold strategies. The timing of
      referral should also be guided by the individual rate of CKD progression. Elderly
      patients with CKD could be referred later to reduce the risk of creating an AVF
      that is never used.

PMID- 23978337
TI  - Use of insulin degludec, a new basal insulin with an ultra-long duration of
      action, in basal-bolus therapy in type 1 and type 2 diabetes.
AB  - Insulin degludec is a new basal insulin analogue with an ultra-long duration of
      action that provides a flat and stable action profile with a duration of action
      greater than 42 hours. Two clinical trials comparing insulin degludec and insulin
      glargine in basal-bolus therapy have recently been published. Both were 52-week,
      multicentre, randomised (3:1), treat-to-target trials in patients already using
      insulin. In both type 1 (n=629) and type 2 diabetes (n=1006), insulin degludec
      was non-inferior to insulin glargine with respect to reduction in HbA1c at 52
      weeks. There were also no significant differences between treatment groups with
      respect to fasting plasma glucose. At similar levels of glycaemic control,
      however, insulin degludec was associated with lower rates of hypoglycaemia than
      insulin glargine. In type 1 diabetes, overall confirmed hypoglycaemia (plasma
      glucose concentration<3.1 mmol/L or severe episodes requiring assistance) was
      similar in the two treatment groups, but nocturnal confirmed hypoglycaemia
      (occurring from 00h01 to 05h59) was 25% lower with insulin degludec (P=0.021). In
      type 2 diabetes, overall confirmed hypoglycaemia was 18% lower (P=0.0359) and
      nocturnal confirmed hypoglycaemia was 25% lower (P=0.0399) with insulin degludec.
      Reductions in hypoglycaemia could reduce physicians' and patients' fears and
      encourage them to titrate insulin more aggressively, and to adhere more closely
      to treatment, with consequent better glycaemic control. The results of these
      trials suggest that insulin degludec has a place in the French clinical setting
      in basal-bolus therapy in type 1 and type 2 diabetes.

PMID- 23978338
TI  - Increased number of Th22 cells and correlation with Th17 cells in peripheral
      blood of patients with IgA nephropathy.
AB  - T-helper (Th) 22 and Th17 cells are involved in the pathogenesis of autoimmune
      diseases. However, the role of Th22 and correlation with Th17 cells in the
      pathophysiology of IgA nephropathy (IgAN) remain unknown. In our study, Th22 and
      Th17 cells in peripheral blood of IgAN patients, non-IgA mesangial proliferative
      glomerulonephritis (non-IgA MsPGN) patients, and healthy controls were measured
      by flow cytometry. The concentration of plasma interleukin-22 (IL-22) was
      examined by enzyme linked immunosorbent assay (ELISA). The results showed that
      Th22 cells, Th17 cells, and plasma IL-22 were significantly elevated in IgAN
      patients compared with non-IgA MsPGN patients and healthy controls. Th22 cells
      showed a positive correlation with the levels of plasma IL-22 in IgAN patients.
      Moreover, a significantly positive correlation between Th22 cells and Th17 in
      IgAN patients was observed. Furthermore, IgAN patients with proteinuria showed a
      higher percentage of Th22 cells than IgAN patients without proteinuria. Our data
      demonstrated that IgAN had increased frequencies of peripheral Th22, Th17 cells
      and plasma IL-22, indicating that Th22 along with Th17 cells are involved in the
      immune responses of IgAN. 

PMID- 23978339
TI  - Yeast community associated with the solid state fermentation of traditional
      Chinese Maotai-flavor liquor.
AB  - Yeasts are the most important group of microorganisms contributing to liquor
      quality in the solid-state fermentation process of Chinese Maotai-flavor liquor.
      There occurred a complex yeast community structure during this process, including
      stages of Daqu (the starter) making, stacking fermentation on the ground and
      liquor fermentation in the pits. In the Daqu making stage, few yeast strains
      accumulated. However, the stacking fermentation stage accumulated nine yeast
      species with different physio-biochemical characteristics. But only four species
      kept dominant until liquor fermentation, which were Zygosaccharomyces bailii,
      Saccharomyces cerevisiae, Pichia membranifaciens, and Schizosaccharomyces pombe,
      implying their important functions in liquor making. The four species tended to
      inhabit in different locations of the stack and pits during stacking and liquor
      fermentation, due to the condition heterogeneity of the solid-state fermentation,
      including the different fermentation temperature profiles and oxygen density in
      different locations. Moreover, yeast population was much larger in the upper
      layer than that in the middle and bottom layers in liquor fermentation, which was
      in accordance with the profile of reducing sugar consumption and ethanol
      production. This was a systematical investigation of yeast community structure
      dynamics in the Maotai-flavor liquor fermentation process. It would be of help to
      understand the fermentative mechanism in solid-state fermentation for Maotai
      flavor liquor. 

PMID- 23978340
TI  - A validated micellar electrokinetic chromatography method for the quantitation of
      dexamethasone, ondansetron and aprepitant, antiemetic drugs, in organogel.
AB  - A micellar electrokinetic chromatography (MEKC) method was developed for the
      determination of three anti-vomiting drugs (aprepitant, dexamethasone and
      ondansetron) in pharmaceutical formulations. The method was optimized using a
      central composite design (CCD). Four main factors (borate buffer concentration,
      pH, methanol content and sodium dodecyl sulfate concentration) were optimized in
      order to obtain best resolutions and peak efficiencies in a minimum runtime. The
      separation was performed in a fused-silica capillary. After optimization, the
      background electrolyte consisted of a borate buffer (62.5mM, pH 8.75) containing
      sodium dodecyl sulfate (77.5mM) and methanol (3.75%). Under these conditions, a
      complete separation of each antiemetic drug and its respective internal standards
      was achieved in 38min. The method was validated with trueness values from 94.9 to
      107.2% and precision results (repeatability and intermediate precision) lower
      than 5.9%. MEKC-UV was the first method allowing the separation of aprepitant,
      dexamethasone and ondansetron and was suitable for the quantitation of these
      three antiemetic drugs in organogel formulations. The rapid sample preparation
      coupled with an automated separation technique make this method convenient for
      quality control of extemporaneous magistral ready-to-use formulation. 

PMID- 23978341
TI  - An integrated metabonomics and transcriptomics approach to understanding
      metabolic pathway disturbance induced by perfluorooctanoic acid.
AB  - Perfluorooctanoic acid (PFOA) is one of the most representative perfluorinated
      compounds and liver is the major organ where PFOA is accumulated. Although the
      multiple toxicities had been reported, its toxicological profile remained
      unclear. In this study, a systems toxicology strategy integrating liquid
      chromatography/mass spectrometry-based metabonomics and transcriptomics analyses
      was applied for the first time to investigate the effects of PFOA on a
      representative Chinese normal human liver cell line L-02, with focusing on the
      metabolic disturbance. Fifteen potential biomarkers were identified on metabolic
      level and most observations were consistent with the altered levels of gene
      expression. Our results showed that PFOA induced the perturbations in various
      metabolic processes in L-02 cells, especially lipid metabolism-related pathways.
      The up-stream mitochondrial carnitine metabolism was proved to be influenced by
      PFOA treatment. The specific transformation from carnitine to acylcarnitines,
      which showed a dose-dependent effect, and the expression level of key genes
      involved in this pathway were observed to be altered correspondingly.
      Furthermore, the down-stream cholesterol biosynthesis was directly confirmed to
      be up-regulated by both increased cholesterol content and elevated expression
      level of key genes. The PFOA-induced lipid metabolism-related effects in L-02
      cells started from the fatty acid catabolism in cytosol, fluctuated to the
      processes in mitochondria, extended to the cholesterol biosynthesis. Many other
      metabolic pathways like amino acid metabolism and tricarboxylic acid cycle might
      also be disturbed. The findings obtained from the systems biological research
      provide more details about metabolic disorders induced by PFOA in human liver. 

PMID- 23978343
TI  - Biomarkers and molecular imaging in gastrointestinal cancers.
AB  - The best means to improve gastrointestinal cancer survival is screening and
      treatment of early lesions. In esophageal adenocarcinoma, it is believed that low
      grade dysplasia and perhaps even high-risk Barrett's esophagus represent the most
      attractive targets for achieving a cure. An issue with Barrett's esophagus is
      that endoscopy alone cannot distinguish Barrett's esophagus from columnar-lined
      epithelium or from areas of low-grade dysplasia. Much effort, therefore, has been
      devoted to discover molecular biomarkers of high-risk states and to develop
      imaging tools for detecting these biomarkers in a manner that could assist real
      time in vivo targeting of sites for biopsy. The strategy we have used is to
      generate stem cell clones from Barrett's esophagus biopsy specimens and to
      compare their gene expression profiles with patient-matched stem cell clones of
      the esophageal squamous epithelia and gastric cardia. It is anticipated that by
      mining the expression data sets of these Barrett's stem cell clones, we will be
      able to identify unique cell surface markers of the Barrett's stem cells against
      which cytotoxic antibodies or aptamers can be developed and used to aid the
      endoscopist in identifying regions of atypia for biopsy, perform a real-time
      diagnosis, stratify patients during the examination, and, ultimately, direct
      therapy in a preemptive manner.

PMID- 23978342
TI  - Patterns of cortical thickness and the Child Behavior Checklist in childhood
      epilepsy.
AB  - The purpose of this investigation was to characterize the neuroanatomical
      correlates (cortical thickness) of variations in parent-reported Child Behavior
      Checklist (CBCL) scores. Ninety children with epilepsy (aged 8-18) underwent
      brain MRI, and their parents completed the CBCL. FreeSurfer-derived measures of
      cortical thickness were examined in relation to the CBCL broad and narrow band
      competence and behavioral problem scales, as well as the newer DSM-oriented
      scales. Parent reports of higher (better) social competence skills were
      associated with increased cortical thickness, especially in frontal regions.
      Parent reports of behavioral problems were associated with patterns of decreased
      cortical thickness that varied as a function of the specific behavioral issue
      under investigation. Congruence of patterns of cortical thinning between the DSM
      oriented scales and conceptually related specific problem scales (e.g., ADHD
      Problems and Attention Problems) was generally weak. The parent-report version of
      the CBCL is associated with variations in cortical thickness among children with
      epilepsy. Anatomic abnormalities specific to selected competence and behavioral
      problem scales can be identified, with more reliable and robust patterns of
      thinning across scales assessing externalizing behaviors, with generally less
      prominent findings on scales assessing internalizing behaviors. 

PMID- 23978344
TI  - Microsporidiosis: an unusual endoscopic finding.

PMID- 23978345
TI  - Patients with cirrhosis and denied liver transplants rarely receive adequate
      palliative care or appropriate management.
AB  - BACKGROUND & AIMS: Patients with cirrhosis who are receiving palliative care and
      are not eligible for liver transplantation (LT) are often hospitalized multiple
      times, with lack of expectations or understanding of death and dying. We
      evaluated how frequently these patients received appropriate and palliative care.
      METHODS: We performed a retrospective study of 102 consecutive adult patients
      (67% men; mean age, 55 years) who were removed from the list for or declined LT
      from January 2005 through December 2010 at the University of Alberta, Canada.
      Patients' medical records were reviewed to determine their access to palliative
      care and relief of symptoms, the appropriateness of the goals for their care, and
      their requirements for acute care services. RESULTS: The patients' median Model
      for End-stage Liver Disease score was 20, and median time from denial of LT to
      death was 52 days (range, 10-332 days). The most common reasons that patients
      were removed from the transplant wait list were noncompliance or substance abuse
      (26%) and severe illness or organ dysfunction (25%). After patients were removed
      from the list, 17% received renal replacement therapy, and 48% were subsequently
      admitted to the intensive care unit. Patients spent a median of 14 days (range, 6
      33 days) in the hospital after they were removed from the transplant wait list.
      On the basis of the Edmonton Symptom Assessment System, 65% of patients had
      evidence of pain, 58% had evidence of nausea, 10% had depression, 36% had
      anxiety, 48% had dyspnea, and 49% had symptoms of anorexia. Twenty-eight percent
      of all the patients had documentation of do not resuscitate status on their
      charts, and only 11% were referred for palliative care. CONCLUSIONS: Patients
      with cirrhosis who have been removed from the wait list for LT are infrequently
      referred for palliative care (~ 10% of cases), although a high percentage have
      pain or nausea. Goals of care and do not resuscitate status are rarely discussed.
      Improved planning of goals of care and access to palliative services are required
      for these patients.

PMID- 23978346
TI  - Treatment of pancreatic cystic neoplasm: surgery or conservative?
AB  - Pancreatic cystic neoplasms (PCNs) are a heterogeneous group of tumors with
      distinct biological features. These neoplasms are now being recognized more
      frequently owing to advances in cross-sectional imaging and increasing awareness.
      Guidelines for treatment of the common and clinically important PCNs frequently
      have been revised in view of the continuing controversies and evolving clinical
      data. This review summarizes the management approaches of the common and
      clinically important PCNs based on current evidence and guidelines. 

PMID- 23978347
TI  - Comparison of total cortisol, free cortisol, and surrogate markers of free
      cortisol in diagnosis of adrenal insufficiency in patients with stable cirrhosis.
AB  - BACKGROUND & AIMS: Measurements of serum levels of total cortisol can
      overestimate the prevalence of adrenal dysfunction in patients with cirrhosis
      because they have low concentrations of corticosteroid-binding globulin and
      albumin. We used measurements of serum total cortisol and serum free cortisol
      after the low-dose short Synacthen test (LDSST) to assess adrenal dysfunction.
      METHODS: We studied 79 patients with stable cirrhosis; adrenal dysfunction was
      defined by peak concentrations of total cortisol <=494 mmol/L and/or peak
      concentrations of free cortisol <=33 nmol/L after the LDSST. We determined free
      cortisol index (FCI) scores and calculated free cortisol levels by using Coolens'
      equation. The Cox regression model was used to assess the relationship between
      adrenal dysfunction and outcomes (death or liver transplant). RESULTS: On the
      basis of measurement of total cortisol, 34% of patients had adrenal dysfunction,
      and on the basis of measurement of free cortisol, 29% had adrenal dysfunction.
      There was agreement between total cortisol and free cortisol levels in 22% of
      patients; in 13%, adrenal dysfunction was diagnosed only on the basis of total
      cortisol and in 6% only on the basis of free cortisol (kappa coefficient, 0.56; P
      < .01). Low concentrations of corticosteroid-binding globulin (21 vs 54 MUg/mL, P
      < .01) led to an overestimation of adrenal dysfunction that was based on
      measurement of total cortisol. Measurements of calculated free cortisol
      constantly overestimated free cortisol concentrations, with variations as large
      as 87% for baseline values and up to 84% after stimulation. Adrenal
      insufficiency, defined by FCI scores <12, was detected in 30% of patients; among
      them, 23% also had subnormal peak levels of free cortisol (kappa coefficient,
      0.70; P < .001). Adrenal dysfunction was not significantly associated with
      patient outcomes, on the basis of Cox model analysis. CONCLUSIONS: Adrenal
      insufficiency, defined by LDSST, is frequent in patients with stable cirrhosis,
      on the basis of measurements of total and free cortisol. FCI scores are better
      than measurement of total cortisol in assessing adrenal function in patients with
      cirrhosis. We did not associate adrenal dysfunction with outcome, but further
      studies are needed.

PMID- 23978348
TI  - Paracentesis is associated with reduced mortality in patients hospitalized with
      cirrhosis and ascites.
AB  - BACKGROUND & AIMS: Diagnostic paracentesis is recommended for patients with
      cirrhosis who are admitted to the hospital for ascites or encephalopathy.
      However, it is not known whether clinicians in the United States adhere to this
      recommendation; a relationship between paracentesis and clinical outcome has not
      been reported. We analyzed a U.S. database to determine the frequency of
      paracentesis and its association with mortality. METHODS: The 2009 Nationwide
      Inpatient Sample (which contains data from approximately 8 million hospital
      discharges each year) was used to identify patients with cirrhosis and ascites
      who were admitted with a primary diagnosis of ascites or encephalopathy. In
      hospital mortality, length of stay, and hospital charges were compared for those
      who did and did not undergo paracentesis. Outcomes were compared for those who
      received an early paracentesis (within 1 day of admission) and those who received
      one later. RESULTS: Of 17,711 eligible admissions, only 61% underwent
      paracentesis. In-hospital mortality was reduced by 24% among patients who
      underwent paracentesis (6.5% vs 8.5%; adjusted odds ratio, 0.55; 95% confidence
      interval, 0.41-0.74). Most paracenteses (66%) occurred <=1 day after admission.
      In-hospital mortality was lower among patients who received early paracentesis
      than those who received it later (5.7% vs 8.1%, P = .049), although this
      difference was not significant after adjustment for confounders (odds ratio,
      1.26; 95% confidence interval, 0.78-2.02). Among patients who underwent
      paracentesis, the mean hospital stay was 14% longer and hospital charges were 29%
      greater than for patients who did not receive the procedure. CONCLUSIONS:
      Paracentesis is underused for patients admitted to the hospital with ascites; the
      procedure is associated with increased short-term survival. These data support
      practice guidelines derived from expert opinion. Studies are needed to identify
      barriers to guideline adherence.

PMID- 23978350
TI  - Risk of cerebrovascular accidents and ischemic heart disease in patients with
      inflammatory bowel disease: a systematic review and meta-analysis.
AB  - BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is associated with an
      increased risk of venous thromboembolic disease. However, it is unclear whether
      IBD modifies the risk of arterial thromboembolic events, including
      cerebrovascular accidents (CVA) and ischemic heart disease (IHD). METHODS: We
      performed a systematic review and meta-analysis of cohort and case-control
      studies that reported incident cases of CVA and/or IHD in patients with IBD and a
      non-IBD control population (or compared with a standardized population). We
      calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS:
      We analyzed data from 9 studies (2424 CVA events in 5 studies, 6478 IHD events in
      6 studies). IBD was associated with a modest increase in the risk of CVA (5
      studies; OR, 1.18; 95% CI, 1.09-1.27), especially among women (4 studies; OR,
      1.28; 95% CI, 1.17-1.41) compared with men (OR, 1.11; 95% CI, 0.98-1.25), and in
      young patients (<40-50 y old). The increase in risk was observed for patients
      with Crohn's disease and in those with ulcerative colitis. IBD also was
      associated with a 19% increase in the risk of IHD (6 studies; OR, 1.19; 95% CI,
      1.08-1.31), both in patients with Crohn's disease and ulcerative colitis. This
      risk increase was seen primarily in women (4 studies; OR, 1.26; 95% CI, 1.18
      1.35) compared with men (OR, 1.05; 95% CI, 0.92-1.21), in young and old patients.
      IBD was not associated with an increased risk of peripheral arterial
      thromboembolic events. Considerable heterogeneity was observed in the overall
      analysis. CONCLUSIONS: IBD is associated with a modest increase in the risk of
      cardiovascular morbidity (from CVA and IHD)-particularly in women. These patients
      should be counseled routinely on aggressive risk factor modification.

PMID- 23978349
TI  - Many patients with interleukin 28B genotypes associated with response to therapy
      are ineligible for treatment because of comorbidities.
AB  - BACKGROUND & AIMS: Interleukin (IL)-28B (interferon-lambda 3) genotype is the
      strongest predictor of response of patients with hepatitis C virus (HCV)
      infection to antiviral therapy. However, patients with HCV infection often have
      physical or mental comorbidities that contraindicate or complicate treatment,
      regardless of their genotype. The potential role of IL28B genotype within the
      context of patients' clinical and social environment is therefore unclear.
      METHODS: We characterized the IL28B genotype (for rs12980275 and rs8099917) in
      308 patients (mean age, 56 y; 25% African American; 38% with advanced-stage
      fibrosis) with genotype 1 HCV infection seen at the Michael E. DeBakey Veterans
      Administration Medical Center in Houston, Texas, from May 1, 2009, through April
      1, 2012. We evaluated their eligibility for antiviral treatment based on clinical
      and social factors such as physical or mental health comorbidity, ongoing alcohol
      or drug use, and noncompliance with treatment evaluation. RESULTS: Of the 308
      subjects, 40% were homozygous for rs12980275 (associated with response to
      therapy), 46% were heterozygous, and 15% were homozygous for alleles associated
      with reduced response to therapy. Overall, 36% of patients were considered to be
      ineligible for treatment; of these, 40% had the rs12980275 genotype. More than
      half of the patients with rs12980275 who were ineligible for treatment were
      excluded because of mental health comorbidities; one-third of these patients had
      advanced fibrosis. The reason(s) for treatment exclusion resolved in only 8% of
      patients during a mean 1.5 years of follow-up evaluation. CONCLUSIONS: In a well
      characterized cohort of patients with HCV, a large proportion (40%) with IL28B
      polymorphisms associated with response to therapy is ineligible for treatment
      because of contraindications. One potential role of IL28B genotype analysis could
      be to identify patients who, although not currently eligible for antiviral
      treatment, could become so by modifying fixable exclusions to treatment.

PMID- 23978351
TI  - Phenotypic features of Crohn's disease associated with failure of medical
      treatment.
AB  - BACKGROUND & AIMS: There is conflicting evidence on the effects of thiopurines
      (azathioprine or mercaptopurine) and anti-tumor necrosis factor (TNF) therapies
      on rates of surgery among patients with Crohn's disease (CD). We aimed to
      identify factors that identify patients who are unlikely to respond to medical
      therapy and will therefore require surgery. METHODS: We performed a retrospective
      study using the Alberta Inflammatory Bowel Disease Consortium registry to
      identify 425 patients diagnosed with CD who received a prescription of a
      thiopurine and/or an anti-TNF agent from a referral center, from July 1, 1975,
      through September 13, 2012. We collected data on CD-related abdominal surgery
      after therapy and disease features when therapy was instituted. Cox proportional
      regression models were used to associate disease features with outcomes after
      adjusting for potential confounders. Risk estimates were presented as hazard rate
      ratios (HRRs) with 95% confidence intervals (CIs). RESULTS: Among patients given
      thiopurines, stricturing disease (adjusted HR, 4.63; 95% CI, 2.00-10.71), ileal
      location (adjusted HR, 6.20; 95% CI, 1.64-23.42), and ileocolonic location
      (adjusted HR, 3.71; 95% CI, 1.08-12.74) at the time of prescription were
      associated significantly with the need for surgery. Prescription of an anti-TNF
      agent after prescription of a thiopurine reduced the risk for surgery, compared
      with patients prescribed only a thiopurine (adjusted HR, 0.41; 95% CI, 0.22
      0.75). Among patients given anti-TNF agents, stricturing (adjusted HR, 6.17; 95%
      CI, 2.81-13.54) and penetrating disease (adjusted HR, 3.39; 95% CI, 1.45-7.92) at
      the time of prescription were associated significantly with surgery. Older age at
      diagnosis (17-40 y) reduced the risk for abdominal surgery (adjusted HR, 0.41;
      95% CI, 0.21-0.80) compared with a younger age group (<=16 y). Surgery before
      drug prescription reduced the risk for further surgeries among patients who
      received thiopurines (adjusted HR, 0.33; 95% CI, 0.13-0.68) or anti-TNF agents
      (adjusted HR, 0.49; 95% CI, 0.25-0.96). Terminal ileal disease location was not
      associated with a stricturing phenotype. CONCLUSIONS: Based on a retrospective
      database analysis, patients prescribed thiopurine or anti-TNF therapy when they
      have a complicated stage of CD are more likely to require surgery. Better patient
      outcomes are achieved by treating CD at early inflammation stages; delayed
      treatment increases rates of treatment failure.

PMID- 23978352
TI  - Effects of the organic acids produced by a lactic acid bacterium in Apis
      mellifera colony development, Nosema ceranae control and fumagillin efficiency.
AB  - The European honey bee Apis mellifera is known to be affected by many parasites
      and pathogens that have great impact over the insect development. Among parasites
      affecting bee health, Nosema ceranae is one of the main biotic factors affecting
      colony populations. As honey bee populations decline, interest in pathogenic and
      mutualistic relationships between bees and microorganisms has increased. The main
      goal of the current study was to assess the effect of the oral administration of
      the metabolites produced by Lactobacillus johnsonii CRL1647 (mainly organic
      acids) supplemented in syrup, on: (I) N. ceranae sporulation dynamics before and
      after fumagillin application, and (II) performance of A. mellifera colonies.
      Different experiments were conducted to evaluate the effects of these bacterial
      metabolites on bees: in vitro administration revealed no toxic effects against
      bees. Colonies fed with the lactic acids incremented their beehive population and
      also the amount of fat bodies per bee. Finally, the organic acids reduced the
      intensity of the pathogen after the second application of treatment as well as
      enhanced the fumagillin efficiency. This study provides important information for
      the development of new control substances against nosemosis. 

PMID- 23978353
TI  - Dissemination of multidrug-resistant Klebsiella pneumoniae clinical isolates with
      various combinations of carbapenemases (NDM-1 and OXA-72) and 16S rRNA methylases
      (ArmA, RmtC and RmtF) in Nepal.

PMID- 23978354
TI  - In vitro activity of tebipenem against Burkholderia pseudomallei.

PMID- 23978355
TI  - Multiple micronutrient deficiencies among patients with intestinal failure during
      and after transition to enteral nutrition.
AB  - OBJECTIVES: To determine the prevalence of deficiencies of specific
      micronutrients (iron, zinc, magnesium, phosphorus, selenium, copper, folate, and
      vitamins A, D, E, and B12) in children with intestinal failure (IF), and to
      identify risk factors associated with developing these deficiencies. STUDY
      DESIGN: This study was a retrospective review of prospectively collected data
      from 178 children with IF managed by the Intestinal Care Center of Cincinnati
      Children's Hospital Medical Center between August 1, 2007, and July 31, 2012.
      Transition to full enteral nutrition (FEN) was defined as the period during which
      the patient received between 20% and 100% of estimated required nutrition
      enterally. FEN was defined as the patient's ability to tolerate 100% estimated
      required nutrition enterally for >2 weeks. RESULTS: Necrotizing enterocolitis was
      the most common cause of IF (27.5%). Iron was the most common micronutrient
      deficiency identified both during (83.9%) and after (61%) successful transition
      to FEN, with a significant reduction in the percentage of patients with iron
      deficiency between these 2 periods (P = .003). Predictors of micronutrient
      deficiency after successful transition to FEN included birth weight (P = .03),
      weight percentile (P = .02), height percentile (P = .04), and duration of
      parenteral nutrition (PN) (P = .013). After multivariate adjustments, only
      duration of PN remained statistically significant (P = .03). CONCLUSION:
      Micronutrient deficiencies persist in patients with IF during and after
      transition to FEN. These data support the need for routine monitoring and
      supplementation of these patients, especially those on prolonged PN.

PMID- 23978356
TI  - Radiosynthesis of N-(4-chloro-3-[(11)C]methoxyphenyl)-2-picolinamide
      ([(11)C]ML128) as a PET radiotracer for metabotropic glutamate receptor subtype 4
      (mGlu4).
AB  - N-(Chloro-3-methoxyphenyl)-2-picolinamide (3, ML128, VU0361737) is an mGlu4
      positive allosteric modulator (PAM), which is potent and centrally penetrating. 3
      is also the first mGlu4 PAM to show efficacy in a preclinical Parkinson disease
      model upon systemic dosing. As a noninvasive medical imaging technique and a
      powerful tool in neurological research, positron emission tomography (PET) offers
      a possibility to investigate mGlu4 expression in vivo under physiologic and
      pathological conditions. We synthesized a carbon-11 labeled ML128 ([(11)C]3) as a
      PET radiotracer for mGlu4, and characterized its biological properties in Sprague
      Dawley rats. [(11)C]3 was synthesized from N-(4-chloro-3-hydroxyphenyl)-2
      picolinamide (2) using [(11)C]CH3I. Total synthesis time was 38+/-2.2min (n=7)
      from the end of bombardment to the formulation. The radioligand [(11)C]3 was
      obtained in 27.7+/-5.3% (n=5) decay corrected radiochemical yield based on the
      radioactivity of [(11)C]CO2. The radiochemical purity of [(11)C]3 was >99%.
      Specific activity was 188.7+/-88.8GBq/mol (n=4) at the end of synthesis (EOS).
      PET images were conducted in 20 normal male Sprague Dawley rats including 11
      control studies, 6 studies blocking with an mGlu4 modulator (4) to investigate
      specificity and 3 studies blocking with an mGlu5 modulator (MTEP) to investigate
      selectivity. These studies showed fast accumulation of [(11)C]3 (peak activity
      between 1-3min) in several brain areas including striatum, thalamus, hippocampus,
      cerebellum, and olfactory bulb following with fast washout. Blocking studies with
      the mGlu4 modulator 4 showed 22-28% decrease of [(11)C]3 accumulation while
      studies of selectivity showed only minor decrease supporting good selectivity
      over mGlu5. Biodistribution studies and blood analyses support fast metabolism.
      Altogether this is the first PET imaging ligand for mGlu4, in which the labeled
      ML128 was used for imaging its in vivo distribution and pharmacokinetics in
      brain. 

PMID- 23978357
TI  - Synthesis and anti-inflammatory activity of aromatic glucosinolates.
AB  - Aromatic GLs are important members of the glucosinolate family of compounds
      because of their potential biological activity and medicinal properties. This
      study has shown success in the high yielding synthesis of some important aromatic
      GLs as well as the results of testing for anti-inflammatory properties of the
      synthetic GLs. 3,4-Dimethoxyphenylglucosinolate was found to be the most active
      anti-inflammatory of the seven glucosinolates assayed. 

PMID- 23978358
TI  - N-Methylanilide and N-methylbenzamide derivatives as phosphodiesterase 10A
      (PDE10A) inhibitors.
AB  - PDE10A is a recently identified phosphodiesterase with a quite remarkable
      localization since the protein is abundant only in brain tissue. Based on this
      unique localization, research has focused extensively on using PDE10A modulators
      as a novel therapeutic approach for dysfunction in the basal ganglia circuit
      including Parkinson's disease, Huntington's disease, schizophrenia, addiction and
      obsessive compulsive disorder. Medicinal chemistry efforts identified the N
      methyl-N-[4-(quinolin-2-ylmethoxy)-phenyl]-isonicotinamide (8) as a nanomolar
      PDE10A inhibitor. A subsequent Lead-optimization program identified analogous N
      methylanilides and their corresponding N-methylbenzamides (29) as potent PDE10A
      inhibitors, concurrently some interesting and unexpected binding modes were
      identified. 

PMID- 23978359
TI  - Design and synthesis of novel 3-substituted-indole derivatives as selective H3
      receptor antagonists and potent free radical scavengers.
AB  - A series of novel 3-substituted-indole derivatives with a benzyl tertiary amino
      moiety were designed, synthesized and evaluated as H3 receptor antagonists and
      free radical scavengers for Alzheimer's disease therapy. Most of these
      synthesized compounds exhibited moderate to potent antagonistic activities in
      CREs driven luciferase assay. In particular, compound 2d demonstrated the most
      favorable H3 receptor antagonistic activity with the IC50 value of 0.049MUM.
      Besides, it also displayed high binding affinity to H3 receptor (Ki=4.26+/
      2.55nM) and high selectivity over other three histamine receptors. Moreover, 2d
      and other two 3-substituted indole derivatives 1d and 3d exerted potent ABTS
      radical cation scavenging capacities similar to melatonin. Above results
      illustrate that 2d is an interesting lead for extensive optimization to explore
      new drug candidate for AD therapy. 

PMID- 23978360
TI  - Peak systolic velocity of pulmonary venous flow and mitral annulus are
      independent predictors of left ventricular global longitudinal strain in patients
      with cardiomyopathy.

PMID- 23978361
TI  - Age adjusted Charlson Co-morbidity Index is an independent predictor of mortality
      over long-term follow-up in infective endocarditis.
AB  - BACKGROUND: Infective endocarditis (IE) is associated with high morbidity and
      mortality. The epidemiology of IE is changing, affecting more elderly patients
      with increased medical comorbidities. We aimed to assess the ability of the age
      adjusted Charlson Co-morbidity Index (ACCI) to predict early and late outcomes.
      METHODS: Between 1998 and 2010, adult patients with definite IE according to the
      modified Duke criteria were identified. The primary outcome was in-hospital and
      all-cause mortality. The secondary outcome was predictors of the primary outcome
      incorporating ACCI. RESULTS: 148 patients with IE were followed up for a mean of
      3.8 +/- 3 years. The mean age was 57 +/- 17 years and 66% were male. In-hospital
      mortality and all-cause mortality were 24 and 47% respectively. Comorbid
      conditions included diabetes mellitus (DM) (21%); ischaemic heart disease (16%);
      heart failure (HF) (14%); renal failure (eGFR <60 ml/min/1.73 m(2)) (19%); and
      anaemia (64%). The most common causative organism was Staphylococcus aureus
      (53%). ACCI was >3 in 59% of patients. Cardiac surgery was performed in 45% of
      patients. On Cox regression analysis, ACCI >3 (HR=3.0 [1.5-6.0], p<0.002), new
      onset HF (HR=2.2 [1.3-3.6], p<0.003), anaemia (HR=1.8 [1.1-3.2], p=0.04) and age
      per decade (HR=1.4 [1.1-1.7]. p=0.004) were independently associated with all
      cause mortality. ACCI >3 was the strongest predictor of in-hospital mortality
      (OR=8.4 [2.8-24], p<0.001). Of the individual ACCI components, prior HF, DM with
      complications and metastatic disease were independent predictors of all-cause
      mortality. CONCLUSION: In-hospital and all-cause mortality of IE remain high. An
      ACCI >3 was a strong predictor of mortality, in addition to age, new HF and
      anaemia.

PMID- 23978362
TI  - Macrophage migration inhibitory factor is associated with vascular dysfunction in
      patients with end-stage renal disease.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) show a high prevalence
      of cardiovascular disease with arterial stiffness, atherosclerosis and
      endothelial dysfunction, leading to increased morbidity and mortality. The
      cytokine macrophage migration inhibitory factor (MIF) exhibits proinflammatory
      and proatherogenic functions and has recently emerged as a major regulator of
      atherogenesis. Studies examining the relationship between circulating MIF levels
      and vascular dysfunction in this high-risk population do not exist. METHODS: In
      patients with ESRD (n = 39) and healthy controls (n = 16) we assessed endothelial
      function by flow-mediated dilation of the brachial artery and arterial stiffness
      (augmentation pressure, augmentation index and pulse pressure) using applanation
      tonometry. High-sensitive Troponin and subendocardial viability ratio were
      determined to assess myocardial injury. RESULTS: Patients with ESRD had impaired
      endothelial function and higher plasma MIF levels. MIF levels negatively
      correlated with endothelial function (r = -0.345, P = 0.031) and positively with
      arterial stiffness indices in patients with ESRD (pulse pressure r = -0.374, P =
      0.019 and augmentation pressure r = -0.423, P = 0.025). In multivariate
      regression models besides age, gender, weight, and heart rate, MIF was an
      independent predictor for arterial stiffness. Impact on myocardial end-organ
      damage was reflected by correlation with high-sensitive Troponin I (r = 0.43, P =
      0.009). CONCLUSION: Our findings show that high MIF plasma levels are associated
      with diminished endothelial function and arterial stiffness and are correlated
      with myocardial injury. Further studies are necessary to investigate whether
      modulation of MIF might have an impact on atherosclerotic disease in this high
      risk population.

PMID- 23978363
TI  - MicroRNAs as novel antiarrhythmic targets for atrial fibrillation.

PMID- 23978364
TI  - Implementation of contemporary oral antiplatelet treatment guidelines in patients
      with acute coronary syndrome undergoing percutaneous coronary intervention: a
      report from the GReek AntiPlatelet rEgistry (GRAPE).
AB  - BACKGROUND: Few data exist about the implementation of contemporary oral
      antiplatelet treatment guidelines in patients with acute coronary syndrome (ACS)
      undergoing percutaneous coronary intervention (PCI). METHODS: GReek AntiPlatelet
      rEgistry (GRAPE), initiated on January 2012, is a prospective, observational,
      multicenter cohort study focusing on contemporary use of P2Y12 inhibitors. In
      1434 patients we evaluated appropriateness of P2Y12 selection initially and at
      discharge by applying an eligibility-assessing algorithm based on P2Y12
      inhibitors' contraindications/specific warnings and precautions. RESULTS:
      Appropriate, less preferable and inappropriate P2Y12 inhibitor selections were
      made initially in 45.8%, 47.2% and 6.6% and at discharge in 64.1%, 29.2% and 6.6%
      of patients, respectively. The selection of clopidogrel was most commonly less
      preferable, both initially (69.7%) and at discharge (75.6%). Appropriate
      selection of newer agents was high initially (79.2%-82.8%), with further increase
      as selection at discharge (89.4%-89.8%). Inappropriate selection of the newer
      agents was 17.2%-20.8% initially, decreasing to 10.2%-10.6% at discharge.
      Conditions and co-medications related to increased bleeding risk, presentation
      with ST elevation myocardial infarction and the absence of reperfusion within the
      first 24h were the most powerful predictors of appropriate P2Y12 selection
      initially, whereas age >=75 years, conditions and co-medications related to
      increased bleeding risk and regional trends mostly affected appropriate P2Y12
      selection at discharge. CONCLUSIONS: In GRAPE, adherence with the recently
      released guidelines on oral antiplatelet therapy was satisfactory. Clopidogrel
      was most commonly used as a less preferable selection, while prasugrel or
      ticagrelor selection was mostly appropriate. Certain factors may predict initial
      and at discharge guideline implementation. Clinical Trial Registration
      clinicaltrials.gov Identifier: NCT01774955 http://clinicaltrials.gov/.

PMID- 23978365
TI  - Incremental prognostic value of cardiac computed tomography angiography in
      asymptomatic aortic stenosis: significance of aortic valve calcium score.
AB  - BACKGROUND: Cardiac computed tomography angiography (CCTA) provides the
      simultaneous evaluation of the aortic valve, myocardium, and coronary arteries.
      In particular, aortic valve calcium score (AVCS) can be accurately measured on
      the same scanning sequence used to measure coronary artery calcification, with no
      additional cost or radiation exposure. We sought to evaluate the prognostic value
      of CCTA measures, including AVCS, in asymptomatic aortic stenosis (AS). METHODS
      AND RESULTS: Sixty-four initially asymptomatic patients with AS with a normal
      ejection fraction were prospectively enrolled and followed for median 29 (IQR=18
      50) months. During follow-up, 27 (42%) patients experienced cardiac events,
      including five cardiac deaths, eleven aortic valve replacements. Multivariate Cox
      proportional hazards analysis identified three CCTA measures as significant
      predictors of cardiac events: aortic valve area (per 0.1cm(2) decrease; hazard
      ratio [HR]: 1.19, 95% confidence interval [CI]: 1.05-1.34); multi-vessel
      obstructive coronary artery disease (HR: 2.84, 95% CI: 1.10-7.32); and AVCS (per
      100; HR: 1.09, 95% CI: 1.04-1.15). Kaplan-Meier analysis showed that patients
      with AVCS greater than or equal to the median value of 723 had significantly
      worse outcomes than those with AVCS less than 723 (p<0.0001). The C-statistic
      value for cardiac events substantially increased when these CCTA measures were
      added to clinical characteristics plus echocardiographic peak transaortic
      velocity (0.913 vs. 0.702, p<0.001). CONCLUSIONS: In patients with asymptomatic
      AS, CCTA measures of valve area, coronary stenosis, and calcification severity
      provide independent and incremental prognostic value after accounting for the
      echocardiographic severity of stenosis.

PMID- 23978366
TI  - Coronary artery bypass grafting in patients with left ventricular dysfunction:
      predictors of long-term survival and impact of surgical strategies.
AB  - BACKGROUND: In the surgical management of ischemic cardiomyopathy, factors
      associated with long-term prognosis after coronary artery bypass grafting (CABG)
      in patients with severe left ventricular (LV) dysfunction are poorly understood.
      This study aimed to determine predictors of clinical outcomes in patients with
      severe LV dysfunction undergoing CABG. METHODS: Out of 6084 patients who
      underwent CABG between 1997 and 2011, 476 patients (aged 62.6 +/- 9.3 years, 100
      females) were identified as having severe LV dysfunction (ejection fraction <=
      35%), preoperatively. All-cause mortality and adverse cardiac events (myocardial
      infarction, repeat revascularization, stroke and hospitalization due to
      cardiovascular causes) were evaluated during a median follow-up period of 55.2
      months (inter-quartile range: 26.4-94.8 months). RESULTS: During the follow-up,
      187 patients (39.3%) died and 126 cardiac events occurred in 104 patients
      (21.8%). Five-year survival and event-free survival rates were 72.1 +/- 2.2% and
      61.3 +/- 2.4%, respectively. On Cox-regression analysis, old age (P < 0.001),
      recent MI (P < 0.001), history of coronary stenting (P = 0.023), decreased
      glomerular filtration rate (P < 0.001), and presence of mitral regurgitation
      (>=moderate) (P = 0.012) or LV wall thinning (P = 0.007) emerged as significant
      and independent predictors of death. After adjustment for important covariates
      affecting outcomes, none of the pump strategy (off-pump vs. on-pump), concomitant
      mitral surgery or surgical ventricular reconstruction (SVR) affected survival or
      event-free survival (P = 0.082 to >0.99). CONCLUSIONS: Long-term survival
      following CABG in patients with severe LV dysfunction was affected by age, renal
      function, recent MI, prior coronary stenting, and presence of mitral
      regurgitation or LV wall thinning. Neither concomitant mitral surgery nor SVR,
      however, had significant influence on clinical outcomes.

PMID- 23978367
TI  - High-sensitivity C-reactive protein and atherosclerotic disease: from improved
      risk prediction to risk-guided therapy.
AB  - There is compelling experimental and clinical evidence suggesting a crucial role
      for inflammation in the initiation and also the progression of atherosclerosis.
      Numerous biomarkers involved at various levels of the inflammation cascade have
      been shown to be associated with adverse cardiovascular outcomes. Yet, to date,
      it is not clear whether inflammation simply accompanies the atherosclerotic
      process or represents a major driver. Among all blood biomarkers, C-reactive
      protein (CRP), the classical acute phase reactant that can be measured with high
      sensitivity (hs) assays seems to be the most promising candidate. It has already
      found its way into the guidelines in primary prevention. Hs-CRP can also be used
      to identify a high-risk group for recurrent events in patients with manifest
      atherosclerosis. Several post hoc analyses of large-scale randomized clinical
      trials testing various statins have indicated that, besides low density
      lipoprotein (LDL) cholesterol, hs-CRP levels might also further aid in tailoring
      statin treatment. The large JUPITER trial has prospectively confirmed these
      findings in primary prevention in patients with elevated hs-CRP but normal LDL
      cholesterol levels. Still, statin therapy is not a specific anti-inflammatory
      regime acting on the inflammation cascade. Thus, to directly test the
      inflammation hypothesis, a novel, more proximally located cytokine-based approach
      is needed. Canakinumab, a fully human monoclonal antibody against interleukin
      1beta, might represent a promising compound in this regard and provide a proof of
      concept. If successful, this may become a novel strategy to treat high-risk
      patients with stable atherosclerotic disease to prevent recurrent events on top
      of standard medical care. 

PMID- 23978368
TI  - Anatomical relationship of coronary sinus/great cardiac vein and left circumflex
      coronary artery along mitral annulus in atrial fibrillation before radiofrequency
      catheter ablation using 320-slice CT.
AB  - PURPOSE: We evaluated anatomical relationships between the coronary sinus and
      great cardiac vein (CS/GCV) and left circumflex coronary artery (LCX) along the
      mitral annulus (MA) in patients with atrial fibrillation (AF) using 320-slice CT.
      METHODS: Fifty-three patients with AF (44 males; mean 63 +/- 11 years; 28
      paroxysmal, 10 persistent, and 15 permanent AF) underwent 320-slice CT. Double
      oblique CT images perpendicular to the MA short axis were created every 10
      degrees  for 36 circumferential sections. The angle of 0 degrees  corresponded to
      the 12 o'clock position. RESULTS: CS/GCV-MA distance was greatest in the
      posterolateral MA. CS/GCV diverged from the LCX more widely in the lateral
      through posterolateral MA than the anterior through anterolateral MA. CS/GCV
      crossed the LCX in 51 patients (96.2%) and left main coronary artery in 2
      patients (3.8%). Median angle of the CS/GCV-LCX crossing point was at 40 degrees 
      but ranged widely (0 degrees  to 150 degrees ) and was more frequent in the
      anterior and anterolateral MA than in the lateral, posterolateral, and posterior
      MA (31.4%, 45.1%, 11.8%, 11.8%, and 0%, respectively; P<0.01). CS/GCV crossed
      over the LCX in 39 patients and under the LCX in 12 patients. Range of the CS/GCV
      LCX overlapping course increased significantly as the CS/GCV-LCX crossing point
      neared the CS ostium. Correlation coefficient between the range of the
      overlapping course and crossing point angle was 0.78. CONCLUSIONS: Anatomical
      relationships between CS/GCV and LCX greatly varied in location and proximity
      among AF patients. Interventional electrophysiologists should know the potential
      risk for LCX injury when radiofrequency energy is delivered within the CS/GCV.

PMID- 23978369
TI  - Effects of foods and beverages on the symptoms of chronic prostatitis/chronic
      pelvic pain syndrome.
AB  - OBJECTIVE: To better elucidate the prevalence of perceived food sensitivity and
      characterize the sensitivity pattern in patients with clinically diagnosed
      chronic prostatitis/chronic pelvic pain syndrome. METHODS: A total of 286 men
      meeting the National Institutes of Health criteria for chronic prostatitis were
      mailed a validated questionnaire designed to detect the effect of foods,
      beverages, and/or supplements on pelvic pain symptoms. The questionnaire assessed
      the effect of 176 individual comestibles on each patient's symptoms. The
      responses were numerically scored on a scale of -2 to +2, and the mean values
      were generated for each comestible. In addition, the participants were asked to
      complete the O'Leary-Sant Symptom and Problem Index and Chronic Prostatitis
      Symptom Index questionnaires. RESULTS: Of the 286 surveys, 95 were returned,
      yielding a response rate of 33.2%. Of those subjects who responded, 47.4%
      reported that the consumption of certain comestibles aggravated their symptoms,
      with the most aggravating being spicy foods, coffee, hot peppers, alcoholic
      beverages, tea, and chili. In contrast, the comestibles that alleviated the
      symptoms the most included docusate, pysllium, water, herbal teas, and
      polycarbophil. CONCLUSION: Many patients with chronic prostatitis/chronic pelvic
      pain syndrome have demonstrable food, beverage, and dietary supplement
      sensitivities. Dietary changes should be considered in the treatment of these
      patients.

PMID- 23978370
TI  - Pyocystis after urinary diversion for incontinence--is a concomitant cystectomy
      necessary?
AB  - OBJECTIVE: To review the incidence of defunctionalized bladder-related
      complications in patients who have had a supravesical urinary diversion for
      intractable urinary incontinence without concomitant cystectomy. MATERIALS AND
      METHODS: We retrospectively analyzed the records of patients requiring urinary
      diversion for intractable urinary incontinence from 1996 to 2011 at our
      institution. Patients were excluded from the cohort if they had evidence of
      bladder outlet obstruction or a cystectomy at time of diversion, or had been
      diverted for active malignancy. Sixty patients underwent a supravesical urinary
      diversion without concomitant cystectomy for intractable urinary incontinence.
      The etiology of the urinary incontinence was overtly neurogenic in 28 patients
      and non-neurogenic in 32 patients. Patients had an average follow-up of 45 months
      (range, 9-96). The indications for surgery, previous surgical interventions,
      complications of surgery, and long-term outcomes, including the incidence of
      pyocystis and the need for secondary cystectomy in the postoperative period were
      reviewed. RESULTS: Four of 60 patients (7%) experienced complications relating to
      the defunctionalized bladder; this included pelvic pain and pyocystis. Only 1
      patient required admission to hospital for treatment of pyocystis, the remaining
      3 patients were successfully managed as outpatients with oral antibiotics or
      analgesics. No patient required a secondary surgical procedure for the
      defunctionalized bladder. CONCLUSION: Pyocystis and the need for a secondary
      cystectomy were rare complications in this cohort; we therefore believe that a
      concomitant cystectomy is unnecessary in patients undergoing supravesical urinary
      diversion for intractable urinary incontinence.

PMID- 23978371
TI  - Melanoma of the glans penis and urethra.
AB  - Primary melanoma of the glans or male urethra is a rare malignant tumor with high
      mortality. We searched PubMed and found 129 articles reporting on 220 patients.
      All articles were case reports or case series. Median patient age was 65 years.
      Median survival was 28 months, with 5-year survival in approximately 10%. All
      patients who survived over 5 years had a localized disease (stage I/A) with
      invasion depth <3-3.5 mm. Wide local excision with sentinel lymph node biopsy is
      the treatment of choice for patients with localized disease. For advanced
      disease, the prognosis is poor. 

PMID- 23978372
TI  - Testicular infarction after angioembolization of an ipsilateral renal
      angiomyolipoma.

PMID- 23978374
TI  - Utility of the Mayo-Portland adaptability inventory-4 for self-reported outcomes
      in a military sample with traumatic brain injury.
AB  - OBJECTIVE: To investigate the psychometric properties of the Mayo-Portland
      Adaptability Inventory-4 (MPAI-4) obtained by self-report in a large sample of
      active duty military personnel with traumatic brain injury (TBI). DESIGN:
      Consecutive cohort who completed the MPAI-4 as a part of a larger battery of
      clinical outcome measures at the time of intake to an outpatient brain injury
      clinic. SETTING: Medical center. PARTICIPANTS: Consecutively referred sample of
      active duty military personnel (N=404) who suffered predominantly mild (n=355),
      but also moderate (n=37) and severe (n=12), TBI. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURE: MPAI-4 RESULTS: Initial factor analysis suggested 2 salient
      dimensions. In subsequent analysis, the ratio of the first and second eigenvalues
      (6.84:1) and parallel analysis indicated sufficient unidimensionality in 26
      retained items. Iterative Rasch analysis resulted in the rescaling of the measure
      and the removal of 5 additional items for poor fit. The items of the final 21
      item Mayo-Portland Adaptability Inventory-military were locally independent,
      demonstrated monotonically increasing responses, adequately fit the item response
      model, and permitted the identification of nearly 5 statistically distinct levels
      of disability in the study population. Slight mistargeting of the population
      resulted in the global outcome, as measured by the Mayo-Portland Adaptability
      Inventory-military, tending to be less reflective of very mild levels of
      disability. CONCLUSIONS: These data collected in a relatively large sample of
      active duty service members with TBI provide insight into the ability of patients
      to self-report functional impairment and the distinct effects of military
      deployment on outcome, providing important guidance for the meaningful
      measurement of outcome in this population.

PMID- 23978373
TI  - trans-Cyclooctene--a stable, voracious dienophile for bioorthogonal labeling.
AB  - Discussed herein is the development and advancement of trans-cyclooctene as a
      tool for facilitating bioorthogonal labeling through reactions with s-tetrazines.
      While a number of strained alkenes have been shown to combine with tetrazines for
      applications in bioorthogonal labeling, trans-cyclooctene enables fastest
      reactivity at low concentration with rate constants in excess of k2=10(6) M(-1)
      s(-1). In the present article, we describe advances in computation and synthesis
      that have enabled applications in chemical biology and nuclear medicine.

PMID- 23978375
TI  - In vivo detection of free radicals in mouse septic encephalopathy using molecular
      MRI and immuno-spin trapping.
AB  - Free radicals are known to play a major role in sepsis. Combined immuno-spin
      trapping and molecular magnetic resonance imaging (MRI) was used to detect in
      vivo and in situ levels of free radicals in murine septic encephalopathy after
      cecal ligation and puncture (CLP). DMPO (5,5-dimethyl pyrroline N-oxide) was
      injected over 6h after CLP, before administration of an anti-DMPO probe (anti
      DMPO antibody bound to albumin-gadolinium-diethylene triamine pentaacetic acid
      biotin MRI targeting contrast agent). In vitro assessment of the anti-DMPO probe
      in oxidatively stressed mouse astrocytes significantly decreased T1 relaxation (p
      < 0.0001) compared to controls. MRI detected the presence of anti-DMPO adducts
      via a substantial decrease in %T1 change within the hippocampus, striatum,
      occipital, and medial cortex brain regions (p < 0.01 for all) in septic animals
      compared to shams, which was sustained for over 60 min (p < 0.05 for all).
      Fluorescently labeled streptavidin was used to target the anti-DMPO probe biotin,
      which was elevated in septic brain, liver, and lungs compared to sham. Ex vivo
      DMPO adducts (qualitative) and oxidative products, including 4-hydroxynonenal and
      3-nitrotyrosine (quantitative, p < 0.05 for both), were elevated in septic brains
      compared to shams. This is the first study that has reported on the detection of
      in vivo and in situ levels of free radicals in murine septic encephalopathy.

PMID- 23978376
TI  - An analysis of the door-to-balloon time in STEMI patients in an underdeveloped
      area of China: a single-centre analysis.
AB  - OBJECTIVES: This study was conducted to break the door-to-balloon time (DTBT)
      into constituent elements, and compared which components prolonged markedly. We
      identified the factors that significantly prolonged the DTBT in an underdeveloped
      area of China. METHODS: The patients were included from January 2008 to December
      2010 in 301 consecutive patients presenting with STEMI in our hospital. We
      analysed the components of total DTB times, such as 'Diagnosis time',
      'Cardiologist consultation time', 'Explain the patient's condition time',
      'Transferring time', 'Preparation of the catheterisation laboratory (CL) time',
      and determined which factors significantly prolonged the DTBT potentially.
      RESULTS: The median DTBT of all patients was 134 (98-186) min. The group was
      divided by the DTBT into two: <=120 min and >120 min. In the <=120 min group,
      more patients (68.1%) presented to our hospital during working hours (p=0.000),
      whereas in the >120 min group, more patients (63.2%) presented out of hours
      (p=0.000). More patients (49.3%) presented when the interventionist was on site
      (p=0.000) in the <=120 min group. In the >120 min group, the times for
      consultation by the cardiologist and explaining the patient's condition to the
      family prolonged markedly, as compared to the <=120 min group (p=0.000) when the
      interventionist was off-duty (OR=4.050, p=0.000) and presentation during non
      working hours (OR=3.334, p=0.000) were significant predictors of >120 min DTB
      times. CONCLUSIONS: In our centre, the time of consultation by the cardiologists
      and explaining the patient's condition to the family accounted for most of the
      delay in reperfusion. A lack of interventionists usually resulted in a delay
      during non-working hours in the CL. Several measures should be taken involving
      asking emergency department physicians to awake CL directly, sending the
      patients' information to the cardiologists, popularising medical knowledge to the
      citizens, and increasing the numbers of interventionists qualified to carry out
      primary percutaneous coronary intervention, should be developed to shorten the
      DTBT.

PMID- 23978377
TI  - The immune cell infiltrate populating meningiomas is composed of mature, antigen
      experienced T and B cells.
AB  - BACKGROUND: Meningiomas often harbor an immune cell infiltrate that can include
      substantial numbers of T and B cells. However, their phenotype and
      characteristics remain undefined. To gain a deeper understanding of the T and B
      cell repertoire in this tumor, we characterized the immune infiltrate of 28
      resected meningiomas representing all grades. METHODS: Immunohistochemistry was
      used to grossly characterize and enumerate infiltrating lymphocytes. A molecular
      analysis of the immunoglobulin variable region of tumor-infiltrating B cells was
      used to characterize their antigen experience. Flow cytometry of fresh tissue
      homogenate and paired peripheral blood lymphocytes was used to identify T cell
      phenotypes and characterize the T cell repertoire. RESULTS: A conspicuous B and T
      cell infiltrate, primarily clustered in perivascular spaces, was present in the
      microenvironment of most tumors examined. Characterization of 294 tumor
      infiltrating B cells revealed clear evidence of antigen experience, in that the
      cardinal features of an antigen-driven B cell response were present. Meningiomas
      harbored populations of antigen-experienced CD4+ and CD8+ memory/effector T
      cells, regulatory T cells, and T cells expressing the immune checkpoint molecules
      PD-1 and Tim-3, indicative of exhaustion. All of these phenotypes were
      considerably enriched relative to their frequency in the circulation. The T cell
      repertoire in the tumor microenvironment included populations that were not
      reflected in paired peripheral blood. CONCLUSION: The tumor microenvironment of
      meningiomas often includes postgerminal center B cell populations. These tumors
      invariably include a selected, antigen-experienced, effector T cell population
      enriched by those that express markers of an exhausted phenotype.

PMID- 23978378
TI  - Human cytomegalovirus immediate early proteins promote degradation of connexin 43
      and disrupt gap junction communication: implications for a role in gliomagenesis.
AB  - A lack of gap junctional intercellular communication (GJIC) is common in cancer.
      Many oncogenic viruses have been shown to downregulate the junctional protein
      connexin 43 (Cx43) and reduce GJIC. Human cytomegalovirus (HCMV) is a ubiquitous,
      species-specific betaherpesvirus that establishes life-long latency after primary
      infection. It encodes two viral gene products, immediate early (IE) proteins IE1
      and IE2, which are crucial in viral replication and pathogenesis of many
      diseases. Emerging evidence demonstrates that HCMV DNA and proteins are highly
      prevalent in glioblastoma multiforme (GBM) and in other tumors, but HCMV's role
      in tumorigenesis remains obscure. In the present study, we examined the effects
      of HCMV infection on Cx43 expression and GJIC as well as the viral mechanism
      mediating the effects in human GBM cells and tissue samples. We found that HCMV
      downregulated Cx43 protein, resulting in disruption of functional GJIC as assayed
      by fluorescent dye transfer assay. We show that both HCMV-IE72 and IE86 mediate
      downregulation of Cx43 by silencing RNA targeting either IE72 or IE86 coupled
      with ganciclovir. This finding was further validated by transfection with
      expression vectors encoding IE72 or IE86, and we show that viral-mediated Cx43
      depletion involved proteasomal degradation. Importantly, we also observed that
      the Cx43 protein levels and IE staining correlated inversely in 10 human GBM
      tissue specimens. Thus, HCMV regulates Cx43 expression and GJIC, which may
      contribute to gliomagenesis. 

PMID- 23978379
TI  - Gene expression signature of non-involved lung tissue associated with survival in
      lung adenocarcinoma patients.
AB  - Lung adenocarcinoma patients of similar clinical stage and undergoing the same
      treatments often have marked interindividual variations in prognosis. These
      clinical discrepancies may be due to the genetic background modulating an
      individual's predisposition to fighting cancer. Herein, we hypothesized that the
      lung microenvironment, as reflected by its expression profile, may affect lung
      adenocarcinoma patients' survival. The transcriptome of non-involved lung tissue,
      excised from a discovery series of 204 lung adenocarcinoma patients, was
      evaluated using whole-genome expression microarrays (with probes corresponding to
      28 688 well-annotated coding sequences). Genes associated with survival status at
      60 months were identified by Cox regression analysis (adjusted for gender, age
      and clinical stage) and retested in a validation series of 78 additional cases.
      RNA-Seq analysis from non-involved lung tissue of 12 patients was performed to
      characterize the different isoforms of candidate genes. Ten genes for which the
      loge-transformed hazard ratios expressed the same direction of effect in the
      discovery (P < 1.0 * 10(-3)) and validation series comprised the gene expression
      signature associated with survival: CNTNAP1, PKNOX1, FAM156A, FRMD8, GALNTL1,
      TXNDC12, SNTB1, PPP3R1, SNX10 and SERPINH1. RNA sequencing highlighted the
      complex expression pattern of these genes in non-involved lung tissue from
      different patients and permitted the detection of a read-through gene fusion
      between PPP3R1 and the flanking gene (CNRIP1) as well as a novel isoform of
      CNTNAP1. Our findings support the hypothesis that individual genetic
      characteristics, evidenced by the expression pattern of non-involved tissue,
      influence the outcome of lung adenocarcinoma patients. 

PMID- 23978381
TI  - How is the blood-nerve barrier involved in the pathogenetic mechanisms of
      multifocal motor neuropathy?

PMID- 23978380
TI  - Diagnosis and management of Marchiafava-Bignami disease: a review of CT/MRI
      confirmed cases.
AB  - OBJECTIVE: Marchiafava-Bignami disease (MBD) is a rare condition mainly
      associated with alcoholism, although it may be mimicked by several other
      disorders that cause corpus callosum lesions. Our objective was to identify
      helpful features for differential diagnosis and assess whether any treatment can
      be recommended. METHODS: We reviewed 122 reports containing data on 153 subjects
      with confirmed MBD that was associated with either alcoholism or malnutrition,
      and 20 reports with data on 53 subjects with conditions mimicking MBD. All the
      cases had been verified antemortem by brain imaging. Unconditional logistic
      regression was used to demonstrate factors that were associated with the outcome
      of MBD. RESULTS: The mimicking conditions were differentiated from MBD by the
      occurrence of solitary and rapidly disappearing splenial lesions; fewer signs and
      symptoms with exception of seizures, hemiparesis and tetraparesis; nystagmus; and
      rapid and complete recovery. MBD occurred most frequently among alcoholics, but
      it was also reported in 11 non-alcoholics (7.2% of all the MBD cases). A better
      outcome was observed among those who were treated within 2 weeks after onset of
      symptoms with parenteral thiamine (p=0.033). CONCLUSIONS: As thiamine deficiency
      is frequently associated with alcoholism, malnutrition and prolonged vomiting; we
      recommend prompt treatment of MBD with parenteral thiamine in such subjects.
      Recovery should be followed by repeated neuropsychological and MRI examinations,
      preferably using diffusion tensor imaging.

PMID- 23978382
TI  - Individual differences in children's private speech: the role of imaginary
      companions.
AB  - Relations between children's imaginary companion status and their engagement in
      private speech during free play were investigated in a socially diverse sample of
      5-year-olds (N=148). Controlling for socioeconomic status, receptive verbal
      ability, total number of utterances, and duration of observation, there was a
      main effect of imaginary companion status on type of private speech. Children who
      had imaginary companions were more likely to engage in covert private speech
      compared with their peers who did not have imaginary companions. These results
      suggest that the private speech of children with imaginary companions is more
      internalized than that of their peers who do not have imaginary companions and
      that social engagement with imaginary beings may fulfill a similar role to social
      engagement with real-life partners in the developmental progression of private
      speech. 

PMID- 23978385
TI  - The paradox of paclitaxel neurotoxicity: Mechanisms and unanswered questions.
AB  - Paclitaxel is a microtubule-binding compound that is widely used as a
      chemotherapeutic in the treatment of common cancers, including breast and ovarian
      cancer. Paclitaxel binding along the length of microtubules stabilizes them and
      suppresses their dynamics, leading to mitotic arrest and apoptosis in dividing
      cells. Though they are not dividing cells, neurons are also susceptible to
      paclitaxel, and paclitaxel exposure results in axonal degeneration. Thus a
      frequent side effect of paclitaxel treatment in patients is peripheral
      neuropathy, which can necessitate dose reductions and have lasting symptoms. An
      understanding of the mechanisms underlying paclitaxel's neurotoxicity is
      important for development of therapeutics to prevent and alleviate the
      neuropathy. Here we will review approaches taken to investigate mechanisms of
      paclitaxel-induced neuropathy and evidence for potential mechanisms of the axonal
      degeneration downstream of or distinct from microtubule stabilization by
      paclitaxel. This article is part of the Special Issue entitled 'The Synaptic
      Basis of Neurodegenerative Disorders'. 

PMID- 23978383
TI  - Decreased vesicular monoamine transporter 2 (VMAT2) and dopamine transporter
      (DAT) function in knockout mice affects aging of dopaminergic systems.
AB  - Dopamine (DA) is accumulated and compartmentalized by the dopamine transporter
      (DAT; SLC3A6) and the vesicular monoamine transporter 2 (VMAT2; SLC18A2). These
      transporters work at the plasma and vesicular membranes of dopaminergic neurons,
      respectively, and thus regulate levels of DA in neuronal compartments that
      include the extravesicular cytoplasmic compartment. DA in this compartment has
      been hypothesized to contribute to oxidative damage that can reduce the function
      of dopaminergic neurons in aging brains and may contribute to reductions in
      dopaminergic neurochemical markers, locomotor behavior and responses to
      dopaminergic drugs that are found in aged animals. The studies reported here
      examined aged mice with heterozygous deletions of VMAT2 or of DAT, which each
      reduce transporter expression to about 50% of levels found in wild-type (WT)
      mice. Aged mice displayed reduced locomotor responses under a variety of
      circumstances, including in response to locomotor stimulants, as well as changes
      in monoamine levels and metabolites in a regionally dependent manner. Several
      effects of aging were more pronounced in heterozygous VMAT2 knockout (KO) mice,
      including aging induced reductions in locomotion and reduced locomotor responses
      to cocaine. By contrast, some effects of aging were reduced or not observed in
      heterozygous DAT KO mice. These findings support the idea that altered DAT and
      VMAT2 expression affect age-related changes in dopaminergic function. These
      effects are most likely mediated by alterations in DA compartmentalization, and
      might be hypothesized to be exacerbated by other factors that affect the
      metabolism of cytosolic DA. This article is part of the Special Issue entitled
      'The Synaptic Basis of Neurodegenerative Disorders'. 

PMID- 23978384
TI  - The effects of acute alcohol administration on the human brain: insights from
      neuroimaging.
AB  - Over the last quarter century, researchers have peered into the living human
      brain to develop and refine mechanistic accounts of alcohol-induced behavior, as
      well as neurobiological mechanisms for development and maintenance of addiction.
      These in vivo neuroimaging studies generally show that acute alcohol
      administration affects brain structures implicated in motivation and behavior
      control, and that chronic intoxication is correlated with structural and
      functional abnormalities in these same structures, where some elements of these
      decrements normalize with extended sobriety. In this review, we will summarize
      recent findings about acute human brain responses to alcohol using neuroimaging
      techniques, and how they might explain behavioral effects of alcohol
      intoxication. We then briefly address how chronic alcohol intoxication (as
      inferred from cross-sectional differences between various drinking populations
      and controls) may yield individual brain differences between drinking subjects
      that may confound interpretation of acute alcohol administration effects. This
      article is part of the Special Issue Section entitled 'Neuroimaging in
      Neuropharmacology'. 

PMID- 23978386
TI  - Hydroxypropyl-beta-cyclodextrin impacts renal and systemic hemodynamics in the
      anesthetized dog.
AB  - Hydroxypropyl-beta-cyclodextrin (HPbetaCD) is a complexation agent used to
      enhance drug solubilization and formulation stability. Although its toxicity is
      well characterized, its cardiovascular effects are less known. To investigate
      them, HPbetaCD was infused intravenously over 10 min in anesthetized dogs (10-40%
      (w/v, i.e. 200-800 mg/kg) in non-denervated animals and at 40% in denervated
      animals). HPbetaCD increased renal arteriolar resistance and decreased renal
      blood flow at all doses, almost immediately after infusion start, more
      drastically in females. A less pronounced increase in total peripheral resistance
      occurred in females only due to sex difference in sympathetic tone. Pulmonary
      hemodynamic parameters remained unaffected, suggesting that the renal effect was
      rather selective. As a consequence of the increased systemic blood pressure,
      heart rate decreased in normal animals without direct effect on cardiac
      conductance. This effect was abolished in denervated animals. This suggests that
      autonomous nervous feedback loops are functional in normal animals and that
      HPbetaCD has no direct chronotropic effect. In conclusion, systemic and renal
      hemodynamic changes should be considered as potential background effects at 200
      400 mg/kg. At higher doses (800 mg/kg), changes are more pronounced and could
      mask/exacerbate hemodynamic response of drug candidate; such doses should be
      avoided in nonclinical safety studies.

PMID- 23978387
TI  - Genotyping and molecular characterization of hepatitis B virus in liver disease
      patients in Kenya.
AB  - Hepatitis B virus (HBV) genotypes are important in both the clinical
      manifestation of disease and treatment response. Although Kenya belongs to the
      African Region (AFR-E) characterized by high mortality and hyperendemicity of
      HBV, there is a paucity of HBV genotyping data. The aim of this study was to
      molecularly characterize the basic core promoter/precore (BCP/PC) and complete
      surface (S) regions of HBV isolated from 61 HBsAg-positive liver disease patients
      attending Kenyatta National Hospital in Nairobi. HBsAg, HBeAg and viral loads
      were determined. HBV DNA was amplified and sequenced from 58/61 patients. In
      addition to the complete genome of two isolates, the BCP/PC and the complete S
      regions of 43 and 38 isolates, respectively were sequenced. Following
      phylogenetic analysis of the S region, 38 isolates clustered with subgenotype A1,
      whereas two isolates clustered with genotype D, one with subgenotype D1 and
      another as an outlier of the clade containing subgenotype D6 and the D/E
      recombinant. When the complete genome of the latter isolate was sequenced it
      clustered with D6. The majority of isolates belonged to serological subtype adw2
      and only four to ayw2. Three distinct groups of subgenotype A1, distinguished by
      different amino acid motifs, circulate in Kenya: two in the African cluster and a
      monophyletic clade in the "Asian" cluster. HBeAg-negativity was a result of
      G1896A in genotype D isolates, whereas in subgenotype A1, the HBeAg-negativity
      was a result of mutations in the Kozak region (1809-1812) or precore start codon
      (1814-1816). Mutations at positions 1762 and 1764 occurred more frequently in HCC
      patients (p<0.05). In conclusion, subgenotypes A1, D1 and D6 circulate in liver
      disease patients in Kenya, with A1 predominating. 

PMID- 23978388
TI  - Complete genome characterization of enterovirus 104 circulating in Northern Italy
      shows recombinant origin of the P3 region.
AB  - Human enterovirus 104 (EV-C104) is a member of the Human Enterovirus species C
      (Family Picornaviridae, Genus Enterovirus) and has been associated with mild
      respiratory syndromes. At present, only two EV-C104 complete genome sequences
      from strains detected in Switzerland and Japan have been deposited in GenBank. In
      this study a complete genome analysis of seven Italian EV-C104 strains was
      carried out. In addition, VP1 sequence analysis was performed in an additional 5
      Italian strains (for a total of 12 strains). The genome length of the seven
      strains was 7406 nucleotides (nt). The seven genomes showed 91.0-96.9% nucleotide
      identity with respect to other available EV-C104 complete genomes. The P1 and P2
      regions of the Italian strains were closely related to EV-C104 identified in
      Switzerland, while the P3 region was closely related to the EV-C117 strain. In
      addition, bootscan analysis showed the presence of one putative recombination
      breakpoint between the P2 and P3 regions. Based on the trees constructed with
      partial VP1/2A nucleotide sequences, as well as the 3D partial coding region
      tree, the Italian strains appear to form a single and independent cluster
      together with the EV-C104 Japanese strain. In conclusion, a complete phylogenetic
      analysis of the relationship between EV-C104 and other known HEV-C strains was
      achieved. In addition, the recombinant origin of EV-C104, which has circulated in
      Italy and Japan, was demonstrated. 

PMID- 23978389
TI  - Evolutionary insights into photoregulation of the cell cycle in the green
      lineage.
AB  - Plant growth depends solely on light energy, which drives photosynthesis. Thus,
      linking growth control to light signals during certain developmental events, such
      as seed or spore germination and organ formation, is a crucial feature that
      plants evolved to use energy efficiently. How light controls the cell cycle
      depends on growth habitats, body plans (unicellular vs. multicellular), and
      photosensors. For example, the photosensors mediating light signaling to promote
      cell division appear to differ between green algae and land plants. In this
      review, we focus on cell-cycle regulation by light and discuss the transition of
      its molecular mechanisms during evolution. Recent advances show that light
      dependent cell-cycle control involves global changes in transcription of cell
      cycle genes, and is mediated by auxin and cytokinin. 

PMID- 23978391
TI  - Agomelatine in the tree shrew model of depression: effects on stress-induced
      nocturnal hyperthermia and hormonal status.
AB  - The antidepressive drug agomelatine combines the properties of an agonist of
      melatonergic receptors 1 and 2 with an antagonist of the 5-HT2C receptor. We
      analyzed the effects of agomelatine in psychosocially stressed male tree shrews,
      an established preclinical model of depression. Tree shrews experienced daily
      social stress for a period of 5 weeks and were concomitantly treated with
      different drugs daily for 4 weeks. The effects of agomelatine (40 mg/kg/day) were
      compared with those of the agonist melatonin (40 mg/kg/day), the inverse 5-HT2C
      antagonist S32006 (10mg/kg/day), and the SSRI fluoxetine (15 mg/kg/day).
      Nocturnal core body temperature (CBT) was recorded by telemetry, and urinary
      norepinephrine and cortisol concentrations were measured. Chronic social stress
      induced nocturnal hyperthermia. Agomelatine normalized the CBT in the fourth week
      of the treatment (T4), whereas the other drugs did not significantly counteract
      the stress-induced hyperthermia. Agomelatine also reversed the stress-induced
      reduction in locomotor activity. Norepinephrine concentration was elevated by the
      stress indicating sympathetic hyperactivity, and was normalized in the stressed
      animals treated with agomelatine or fluoxetine but not in those treated with
      melatonin or S32006. Cortisol concentration was elevated by stress but returned
      to basal levels by T4 in all animals, irrespective of the treatment. These
      observations show that agomelatine has positive effects to counteract stress
      induced physiological processes and to restore the normal rhythm of nocturnal
      CBT. The data underpin the antidepressant properties of agomelatine and are
      consistent with a distinctive profile compared to its constituent pharmacological
      components and other conventional agents.

PMID- 23978392
TI  - Dopaminergic modulation of the reward system in schizophrenia: a placebo
      controlled dopamine depletion fMRI study.
AB  - BACKGROUND: The brain reward circuitry innervated by dopamine is critically
      disturbed in schizophrenia. This study aims to investigate the role of dopamine
      related brain activity during prediction of monetary reward and loss in first
      episode schizophrenia patients. METHODS: We measured blood-oxygen-level dependent
      (BOLD) activity in 10 patients with schizophrenia (SCH) and 12 healthy controls
      during dopamine depletion with alpha-methylparatyrosine (AMPT) and during a
      placebo condition (PLA). RESULTS: AMPT reduced the activation of striatal and
      cortical brain regions in SCH. In SCH vs. controls reduced activation was found
      in the AMPT condition in several regions during anticipation of reward and loss,
      including areas of the striatum and frontal cortex. In SCH vs. controls reduced
      activation of the superior temporal gyrus and posterior cingulate was observed in
      PLA during anticipation of rewarding stimuli. PLA patients had reduced activation
      in the ventral striatum, frontal and cingulate cortex in anticipation of loss.
      The findings of reduced dopamine-related brain activity during AMPT were verified
      by reduced levels of dopamine in urine, homovanillic-acid in plasma and increased
      prolactin levels. CONCLUSIONS: Our results indicate that dopamine depletion
      affects functioning of the cortico-striatal reward circuitry in SCH. The findings
      also suggest that neuronal functions associated with dopamine neurotransmission
      and attribution of salience to reward predicting stimuli are altered in
      schizophrenia.

PMID- 23978390
TI  - Plasmodesmata dynamics are coordinated by intracellular signaling pathways.
AB  - Membrane-lined channels called plasmodesmata (PD) connect the cytoplasts of
      adjacent plant cells across the cell wall, permitting intercellular movement of
      small molecules, proteins, and RNA. Recent genetic screens for mutants with
      altered PD transport identified genes suggesting that chloroplasts play crucial
      roles in coordinating PD transport. Complementing this discovery, studies
      manipulating expression of PD-localized proteins imply that changes in PD
      transport strongly impact chloroplast biology. Ongoing efforts to find genes that
      control root and stomatal development reveal the critical role of PD in enforcing
      tissue patterning, and newly discovered PD-localized proteins show that PD
      influence development, intracellular signaling, and defense against pathogens.
      Together, these studies demonstrate that PD function and formation are tightly
      integrated with plant physiology. 

PMID- 23978393
TI  - Water in Photosystem II: structural, functional and mechanistic considerations.
AB  - Water is clearly important for the functioning of Photosystem II (PSII). Apart
      from being the very substrate that needs to be transported in this water
      oxidation enzyme, water is also vital for the transport of protons to and from
      the catalytic center as well as other important co-factors and key residues in
      the enzyme. The latest crystal structural data of PSII have enabled detailed
      analyses of the location and possible function of water molecules in the enzyme.
      Significant progress has also been made recently in the investigation of channels
      and pathways through the protein complex. Through these studies, the mechanistic
      significance of water for PSII is becoming increasingly clear. An overview and
      discussion of key aspects of the current research on water in PSII is presented
      here. The role of water in three other systems (aquaporin, bacteriorhodopsin and
      cytochrome P450) is also outlined to illustrate further points concerning the
      central significance that water can have, and potential applications of these
      ideas for continued research on PSII. It is advocated that water be seen as an
      integral part of the protein and far from a mere solvent. 

PMID- 23978394
TI  - Predominant typologies of psychopathology in the United States: a latent class
      analysis.
AB  - BACKGROUND: Latent class analysis (LCA) offers a parsimonious way of classifying
      common typologies of psychiatric comorbidity. We used LCA to identify the nature
      and correlates of predominant typologies of Axis I and II disorders in a large
      and comprehensive population-based sample of U.S. adults. METHODS: We analyzed
      data from Wave 2 of the National Epidemiologic Survey on Alcohol and Related
      Conditions (2004-2005; n = 34,653), a population-based sample of U.S. adults. We
      derived latent classes based on all assessed Axis I and II disorders and examined
      the relationship between the identified Axis I classes and lifetime psychiatric
      disorders and suicide attempts, and physical and mental health-related quality of
      life. RESULTS: A four-class solution was optimal in characterizing predominant
      typologies of both Axis I and II disorders. For Axis I disorders, these included
      low psychopathology (n = 28,935, 84.0%), internalizing (n = 3693, 9.9%),
      externalizing (n = 1426, 4.5%), and high psychopathology (n = 599, 1.6%) classes.
      For Axis II disorders, these included no/low personality disorders (n = 31,265,
      90.9%), obsessive/paranoid (n = 1635, 4.6%), borderline/dysregulated (n = 1319,
      3.4%), and highly comorbid (n = 434, 1.1%) classes. Compared to the low
      psychopathology class, all other Axis I classes had significantly increased odds
      of mental disorders, elevated Axis II classes, suicide attempts and poorer
      quality of life, with the high psychopathology class having the overall highest
      rates of these correlates, with the exception of substance use disorders.
      Compared to the low psychopathology class, the internalizing and externalizing
      classes had increased rates of mood and anxiety disorders, and substance use
      disorders, respectively. CONCLUSION: Axis I and II psychopathology among U.S.
      adults may be best represented by four predominant typologies. Characterizing co
      occurring patterns of psychopathology using person-based typologies represents a
      higher-order classification system that may be useful in clinical and research
      settings.

PMID- 23978395
TI  - Temporal lobe and inferior frontal gyrus dysfunction in patients with
      schizophrenia during face-to-face conversation: a near-infrared spectroscopy
      study.
AB  - Schizophrenia (SC) is marked by poor social-role performance and social-skill
      deficits that are well reflected in daily conversation. Although the mechanism
      underlying these impairments has been investigated by functional neuroimaging,
      technical limitations have prevented the investigation of brain activation during
      conversation in typical clinical situations. To fill this research gap, this
      study investigated and compared frontal and temporal lobe activation in patients
      with SC during face-to-face conversation. Frontal and temporal lobe activation in
      29 patients and 31 normal controls (NC) (n = 60) were measured during 180-s
      conversation periods by using near-infrared spectroscopy (NIRS). The grand
      average values of oxyhemoglobin concentration ([oxy-Hb]) changes during task
      performance were analyzed to determine their correlation with clinical variables
      and Positive and Negative Syndrome Scale (PANSS) subscores. Compared to NCs,
      patients with SC exhibited decreased performance in the conversation task and
      decreased activation in both the temporal lobes and the right inferior frontal
      gyrus (IFG) during task performance, as indicated by the grand average of [oxy
      Hb] changes. The decreased activation in the left temporal lobe was negatively
      correlated with the PANSS disorganization and negative symptoms subscores and
      that in the right IFG was negatively correlated with illness duration, PANSS
      disorganization, and negative symptom subscores. These findings indicate that
      brain dysfunction in SC during conversation is related to functional deficits in
      both the temporal lobes and the right IFG and manifests primarily in the form of
      disorganized thinking and negative symptomatology.

PMID- 23978396
TI  - Impact of mood stabilizers and antiepileptic drugs on cytokine production in
      vitro.
AB  - Changes within the immune system have been reported to contribute to the
      pathophysiology of bipolar disorder and epilepsy. Interestingly, overlapping
      results regarding the cytokine system have been found for both diseases, namely
      alterations of interleukins IL-1beta, IL-2, IL-4, IL-6, and tumor necrosis factor
      alpha (TNF-alpha). However, the effect of mood stabilizers and antiepileptic
      drugs (AEDs) on these cytokines has not been systematically evaluated, and their
      effect on IL-17 and IL-22, other immunologically important cytokines, has not
      been reported. Therefore, we systematically measured levels of IL-1beta, IL-2, IL
      4, IL-6, IL-17, IL-22 and TNF-alpha in stimulated blood of 14 healthy female
      subjects in a whole blood assay using the toxic shock syndrome toxin TSST-1 as
      stimulant. Blood was supplemented with the mood stabilizers or antiepileptic
      drugs primidone (PRM), carbamazepine (CBZ), levetiracetam (LEV), lamotrigine
      (LTG), valproic acid (VPA), oxcarbazepine (OXC), topiramate (TPM), phenobarbital
      (PB), lithium, or no drug. IL-1beta production was significantly decreased by
      PRM, CBZ, LEV, LTG, OXC, PB and lithium. IL-2 significantly decreased by PRM,
      CBZ, LEV, LTG, VPA, OXC, TPM and PB. IL-22 significantly increased by PRM, CBZ,
      LEV, OXC, TPM and lithium and decreased by VPA. TNF-alpha production
      significantly decreased under all applied drugs. The mechanism of action and side
      effects of mood stabilizers and AEDs may involve modulation of IL-1beta, IL-2, IL
      22 and TNF-alpha signaling pathways. IL-22 may be a research target for specific
      therapeutic effects of mood stabilizers and AEDs. These drugs might influence
      cytokine production by modulating ion channels and gamma-aminobutyric acid (GABA)
      receptors of immune cells. 

PMID- 23978397
TI  - Concomitant, sequential, and hybrid therapy for Helicobacter pylori: which one is
      the correct answer?

PMID- 23978398
TI  - Sensory profiles obtained from parental reports correlate with independent
      assessments of development in very preterm children at 2 years of age.
AB  - BACKGROUND: Very preterm (VPT) children have different sensory profiles than term
      born controls, but how the sensory profiles in VPT children relate to development
      has not been reported. AIM: The aim of this study was to examine the relationship
      between VPT infant sensory profiles and concurrent developmental outcomes at 2
      years' corrected age. STUDY DESIGN: Cohort study. SUBJECTS: 243 children <30
      weeks' gestation. OUTCOME MEASURES: Primary caregivers completed the
      Infant/Toddler Sensory Profile Questionnaire to obtain information on sensory
      processing at 2 years of age. Independent observers assessed the child's
      neurodevelopment with either the Mental Developmental Index (MDI) and Psychomotor
      Developmental Index (PDI) of the Bayley Scales of Infant Development version 2
      (Bayley 2) or the Cognition, Language and Motor Composites of the Bayley Scales
      of Infant and Toddler Development version 3 (Bayley 3). RESULTS: A stronger Low
      Registration pattern correlated with lower MDI and PDI scores and a stronger
      Sensation Avoiding pattern correlated with a lower PDI score. A stronger Low
      Registration pattern correlated with a lower Language Composite score. More
      frequent visual and oral sensory processing behaviours were associated with
      higher performance on the MDI and PDI, with more frequent auditory sensory
      processing behaviours also associated with higher PDI scores. More frequent
      auditory, touch and oral sensory processing behaviours were associated with
      improved outcomes on the Language Composite and more frequent auditory, touch and
      vestibular processing behaviours correlated with improved outcomes on the
      Cognition Composite. A secondary analysis using a computed MDI score derived from
      the Bayley 3 scores did not substantially alter any conclusions. CONCLUSION(S):
      Different sensory profile patterns obtained from parental reports of VPT children
      are associated with various aspects of neurodevelopment at 2 years of age,
      obtained from independent assessment.

PMID- 23978399
TI  - Systematic analysis of the development of the ductus venosus in wild type mouse
      and human embryos.
AB  - BACKGROUND: Doppler flow velocities of the ductus venosus are increasingly used
      to assess fetal increased nuchal translucency, growth-restriction and
      monochorionic twins, and might contribute to screening for cardiac defects. It is
      disputed whether a sphincter at the ductus venosus inlet actively regulates blood
      flow. AIMS: This study aims to define the morphogenesis of the developing mouse
      and human ductus venosus and to address the existence of a sphincter. STUDY
      DESIGN: The presence of endothelium, smooth muscle, elastic fibers and nerves in
      the ductus venosus of E10.5-15.5 mouse embryos and in three corresponding human
      embryos (CS16, CS19 and CS23) was examined using immunohistochemistry. Three
      dimensional reconstructions of the ductus venosus of E11.5-15.5 mouse and CS14-23
      human embryos were generated and examined. RESULTS: The ductus venosus lumen was
      narrowed from ventral-caudal to dorsal-cranial in E13.5-15.5 mouse and CS16-23
      human embryos. Mouse embryos showed positive endothelial Pecam1 expression from
      E11.5-15.5 and smooth muscle actin staining in the ventral-caudal part of the
      ductus venosus from E12.5-15.5. At all developmental stages, elastic fiber and
      nerve marker expression was not detected in the ductus venosus (Fig. 2). In human
      embryos endothelial Pecam1 and smooth muscle actin expression was found in the
      ductus venosus from CS16 and CS19 onwards. Elastic fiber and nerve marker
      expression was not detected in all stages (Fig. 4). Morphogenesis and staining
      results of the ductus venosus were similar in both species. CONCLUSIONS: The
      ductus venosus lacks a sphincter at its inlet as no accumulation of smooth muscle
      cells, elastic fibers or nerve innervation was found in mouse embryos from E11.5
      15.5 and in human embryos from CS14-23.

PMID- 23978400
TI  - TMPRSS4 upregulates uPA gene expression through JNK signaling activation to
      induce cancer cell invasion.
AB  - TMPRSS4 is a novel type II transmembrane serine protease that is highly expressed
      in pancreatic, thyroid, colon, and other cancer tissues. Previously, we
      demonstrated that TMPRSS4 mediates tumor cell invasion, migration, and
      metastasis. However, the mechanisms by which TMPRSS4 contributes to invasion are
      not fully understood. Here, we demonstrated that TMPRSS4 induced the
      transcription of the urokinase-type plasminogen activator (uPA) gene through
      activating the transcription factors Sp1, Sp3, and AP-1 in mainly a JNK-dependent
      manner and that the induction of uPA was required for TMPRSS4-mediated cancer
      cell invasion and signaling events. In addition, the uPA receptor was involved in
      TMPRSS4-induced signaling activation and subsequent uPA expression probably
      through its association with TMPRSS4 on the cell surface. Immunohistochemical
      analysis showed that uPA expression was significantly correlated with TMPRSS4
      expression in human lung and prostate cancers. These observations suggest that
      TMPRSS4 is an important regulator of uPA gene expression; the upregulation of uPA
      by TMPRSS4 contributes to invasion and may represent a novel mechanism for the
      control of invasion. 

PMID- 23978401
TI  - Domain-specific phosphomimetic mutation allows dissection of different protein
      kinase C (PKC) isotype-triggered activities of the RNA binding protein HuR.
AB  - The ubiquitous mRNA binding protein human antigen R (HuR) participates in the
      post-transcriptional regulation of many AU-rich element (ARE)-bearing mRNAs.
      Previously, by using in vitro kinase assay, we have identified serines (Ser) 158,
      221 and 318 as targets of protein kinase C (PKC)-triggered phosphorylation. In
      this study, we tested whether GFP- or GST-tagged HuR constructs bearing a
      phosphomimetic Ser (S)-to-Asp (D) substitution at the different PKC target sites,
      would affect different HuR functions including HuR nucleo-cytoplasmic
      redistribution and binding to different types of ARE-containing mRNAs. The
      phosphomimetic GFP-tagged HuR protein bearing a phosphomimetic substitution in
      the hinge region of HuR (HuR-S221D) showed an increased cytoplasmic abundance
      when compared to wild-type HuR. Conversely, data from in vitro kinase assay and
      electrophoretic mobility shift assay (EMSA), implicates that phosphorylation at
      Ser 221 is not relevant for mRNA binding of HuR. Quantification of in vitro
      binding affinities of GST-tagged wild-type HuR and corresponding HuR proteins
      bearing a phosphomimetic substitution in either RRM2 (HuR-S158D) or in RRM3 (HuR
      S318D) by microscale thermophoresis (MST) indicates a specific binding of wild
      type HuR to type I, II or type III-ARE-oligonucleotides in the high nanomolar
      range. Interestingly, phosphomimetic mutation at position 158 or 318 had a
      negative influence on HuR binding to type I- and type II-ARE-mRNAs whereas it
      significantly enhanced HuR affinity to a type III-ARE substrate. Our data suggest
      that differential phosphorylation of HuR by PKCs at different HuR domains
      coordinates subcellular HuR distribution and leads to a preferential binding to U
      rich bearing target mRNA. 

PMID- 23978402
TI  - Effects of acute and subchronic AT1 receptor blockade on cardiovascular,
      hydromineral and neuroendocrine responses in female rats.
AB  - Female Wistar rats were ovariectomized (OVX) and separated into two groups that
      received either estradiol cypionate (EC, 40 MUg/kg, sc; OVX-EC) or vehicle (corn
      oil, sc; OVX-oil) for 14 consecutive days. On the 7th day of treatment, a subset
      of animals from both the OVX-oil and OVX-EC groups was subjected to subchronic
      losartan (AT1 receptor antagonist) treatment (0.1g/L in drinking water; ~15
      mg/kg/day) for 7 days. Other group of OVX-oil and OVX-EC rats was submitted to an
      acute losartan injection (100mg/kg, ip) on the 14th day of hormone replacement.
      In both protocols, the following parameters were measured: I) mean arterial
      pressure (MAP) and heart rate (HR); II) water and 0.3M saline intake; III)
      angiotensin II (ANG II), atrial natriuretic peptide (ANP), vasopressin (AVP) and
      oxytocin (OT) plasma concentrations; and IV) urinary and plasma sodium
      concentrations. Acute AT1 blockade induced a significant reduction in the MAP in
      the OVX rats, resulting in increased HR and water intake, which were attenuated
      by estradiol therapy. Acute AT1 blockade also increased ANG II and OT and reduced
      ANP plasma concentrations, with no changes in AVP secretion. In addition, acute
      hypotension was accompanied by a decrease in natriuresis, which was unaltered by
      estradiol. Subchronic AT1 blockade induced a significant decrease in MAP without
      changing HR in both groups. Additionally, subchronic losartan treatment induced
      sodium appetite in OVX rats. Prolonged AT1 blockade increased ANG II and AVP and
      reduced ANP plasma concentrations. Moreover, it increased natriuresis but did not
      alter plasma OT concentrations. Finally, estradiol treatment attenuated the
      increase in salt intake and plasma ANG II concentrations induced by subchronic
      AT1 blockade. In conclusion, our results suggest differential adaptive responses
      to the acute or subchronic losartan treatment in OVX and OVX-EC rats.

PMID- 23978403
TI  - Objective evidence of myocardial ischemia in patients with posttraumatic stress
      disorder.
AB  - BACKGROUND: Patients with posttraumatic stress disorder (PTSD) are at increased
      risk for cardiovascular disease (CVD), but few studies have included objective
      measures of CVD and how PTSD causes CVD remains unknown. We sought to determine
      the association between PTSD and objectively assessed CVD and examine potential
      underlying mechanisms. METHODS: Outpatients from two Veterans Affairs Medical
      Centers were enrolled from 2008 to 2010. Posttraumatic stress disorder was
      identified using the Clinician Administered PTSD Scale, and standardized exercise
      treadmill tests were performed to detect myocardial ischemia. RESULTS: Of the 663
      participants with complete data, ischemia was present in 17% of patients with
      PTSD versus 10% of patients without PTSD (p = .006). The association between PTSD
      and ischemia remained significant after adjusting for potential confounders (age,
      sex, prior CVD) and mediators (traditional cardiac risk factors, C-reactive
      protein, obesity, alcohol use, sleep quality, social support, and depression),
      adjusted odds ratio (OR) 2.42, 95% confidence interval (CI) 1.39 to 4.22, p =
      .002. Findings remained significant when those with prior CVD were excluded
      (fully adjusted OR 2.24, 95% CI 1.20-4.18, p = .01) and when continuous PTSD
      symptom score was used as the predictor (fully adjusted OR per 10-point change in
      Clinician Administered PTSD Scale score 1.12, 95% CI 1.03-1.22, p = .01).
      CONCLUSIONS: Posttraumatic stress disorder was associated with ischemic changes
      on exercise treadmill tests independent of traditional cardiac risk factors, C
      reactive protein, and several health behaviors and psychosocial risk factors,
      suggesting additional mechanisms linking PTSD and ischemia should be explored.
      The association of PTSD and ischemia among patients without known CVD highlights
      an opportunity for early interventions to prevent progression of cardiovascular
      disease.

PMID- 23978404
TI  - Anatomical characteristics of the cerebral surface in bulimia nervosa.
AB  - BACKGROUND: The aim of this study was to examine morphometric features of the
      cerebral surface in adolescent and adult female subjects with bulimia nervosa
      (BN). METHODS: Anatomical magnetic resonance images were acquired from 34
      adolescent and adult female subjects with BN and 34 healthy age-matched control
      subjects. We compared the groups in the morphological characteristics of their
      cerebral surfaces while controlling for age and illness duration. RESULTS:
      Significant reductions of local volumes on the brain surface were detected in
      frontal and temporoparietal areas in the BN compared with control participants.
      Reductions in inferior frontal regions correlated inversely with symptom
      severity, age, and Stroop interference scores in the BN group. CONCLUSIONS: These
      findings suggest that local volumes of inferior frontal regions are smaller in
      individuals with BN compared with healthy individuals. These reductions along the
      cerebral surface might contribute to functional deficits in self-regulation and
      to the persistence of these deficits over development in BN.

PMID- 23978405
TI  - 'Living within your limits': activity restriction in older people experiencing
      chronic pain.
AB  - BACKGROUND: although maintaining activity is key to successful pain management,
      and important to health and wellbeing, it is known that older people in pain
      frequently alter or reduce activity levels. A 'fear-avoidance' model is often
      used to explain avoidance of activity in the face of pain. However, this model is
      not intended to take account of the wider context in which activity changes take
      place, nor older people's own explanations for their behaviour. OBJECTIVE: to
      investigate the reasons why older people in the community adjust their activity
      levels when living with chronic pain. METHODS: thirty-one people aged between 67
      and 92 were purposively sampled from respondents to a community-based cross
      sectional survey. All participants had reported long-term pain and were
      interviewed about this. Data were collected and analysed using a qualitative
      constructivist grounded theory approach. FINDINGS: explanations for deliberative
      reduction or ceasing of activities reflected a desire to prevent pain
      exacerbation, thereby avoiding medical intervention. It also reflected a desire
      to safeguard autonomy in the face of pain in older age. Restrictions were often
      rationalised as normal in older age, although co-existing accounts of
      perseverance and frustration with limitation were also evident. CONCLUSIONS: a
      rational desire to avoid pain exacerbation and medical intervention motivated
      restrictions to activity. However, deliberative limitation of activity has the
      potential to compromise autonomy by increasing social isolation and de
      conditioning. Supporting older people with pain to be active requires sensitivity
      to the function of activity restriction, especially as a means of preventing
      deterioration.

PMID- 23978406
TI  - Do older patients find multi-compartment medication devices easy to use and which
      are the easiest?
AB  - BACKGROUND: multi-compartment medication devices (MMDs) are widely used,
      primarily by older people, to aid correct-medication taking. Several MMD types
      are available yet little is known about the ease with which patients with varying
      functional ability use these devices and whether some types are easier than
      others. Such knowledge would assist healthcare practitioners in advising patients
      on a suitable choice of device. OBJECTIVE: this study investigates the ease with
      which patients with differing functional ability use three types of MMD. METHOD:
      participants were recruited from an older person's medical ward. Demographic and
      medication information, cognitive function, visual acuity and manual dexterity
      were recorded. The Venalink(r), Nomad Clear(r) and Dosett(r) MMDs were tested.
      Participants rated each MMD according to text readability, ease of opening, ease
      of medication removal, transportability and overall rating. These ratings were
      compared between MMDs for all patients and for subgroups with differing
      functional abilities. RESULTS: the MMDs were trialled by 50 patients; the
      majority rated text readability well but rated MMDs poorly according to the other
      criteria. Cognitively impaired participants may encounter difficulties in opening
      and removing medication from Venalink(r) and Nomad(r). The Dosett(r) consistently
      rated better across all criteria. Transportability was the most influential
      criterion for overall MMD usability. CONCLUSION: the poor patient rating of MMDs
      which are widely used in practice is of concern. Some MMDs may be difficult to
      open and access, especially for patients with cognitive impairment. This offers
      some guidance to health professionals in advising patients on MMD choice however,
      overall MMD rating appears dominated by transportability.

PMID- 23978407
TI  - Effectiveness of a multi-component intervention to reduce delirium incidence in
      elderly care wards.
AB  - OBJECTIVE: to examine the effect of a multi-component, delirium prevention
      intervention on rates of incident delirium for patients admitted to specialist
      elderly care wards. DESIGN: 'before' and 'after' study. SETTING: three specialist
      elderly care wards in a general hospital. SUBJECTS: older people admitted as
      emergencies. METHODS: a multi-component delirium prevention intervention that
      targeted delirium risk factors was implemented by clinical staff. Demographic
      information and assessments for delirium risk factors were recorded by research
      staff within 24 h of admission to the ward. New onset (incident) delirium was
      diagnosed by daily research staff assessments using the Confusion Assessment
      Method and Delirium Rating Scale-Revised-98. RESULTS: a total of 436 patients
      were recruited (249 in the 'before' and 187 in the 'after' group). Incident
      delirium was significantly reduced ('before' = 13.3%; 'after' = 4.6%; P = 0.006).
      Delirium severity and duration were significantly reduced in the 'after' group.
      Mortality, length of stay, activities of daily living score at discharge and new
      discharge to residential or nursing home rates were similar for both groups.
      CONCLUSIONS: a multi-component, delirium prevention intervention directed at
      delirium risk factors and implemented by local clinical staff can reduce incident
      delirium on specialist elderly care wards.

PMID- 23978408
TI  - Comparison of effects between home visits with telephone calls and telephone
      calls only for transitional discharge support: a randomised controlled trial.
AB  - BACKGROUND: home visits and telephone calls are two often used approaches in
      transitional care but their differential effects are unknown. OBJECTIVE: to
      examine the overall effects of a transitional care programme for discharged
      medical patients and the differential effects of telephone calls only. DESIGN:
      randomised controlled trial. SETTING: a regional hospital in Hong Kong.
      PARTICIPANTS: patients discharged from medical units fitting the inclusion
      criteria (n = 610) were randomly assigned to: control ('control', n = 210), home
      visits with calls ('home', n = 196) and calls only ('call', n = 204).
      INTERVENTION: the home groups received alternative home visits and calls and the
      call groups calls only for 4 weeks. The control group received two placebo calls.
      The nurse case manager was supported by nursing students in delivering the
      interventions. RESULTS: the home visit group (after 4 weeks 10.7%, after 12 weeks
      21.4%) and the call group (11.8, 20.6%) had lower readmission rates than the
      control group (17.6, 25.7%). Significance differences were detected in intention
      to-treat (ITT) analysis for the home and intervention group (home and call
      combined) at 4 weeks. In the per-protocol analysis (PPA) results, significant
      differences were found in all groups at 4 weeks. There was significant
      improvement in quality of life, self-efficacy and satisfaction in both ITT and
      PPA for the study groups. CONCLUSIONS: this study has found that bundled
      interventions involving both home visits and calls are more effective in reducing
      readmissions. Many of the transitional care programmes use all-qualified nurses,
      and this study reveals that a mixed skills model seems to bring about positive
      effects as well.

PMID- 23978409
TI  - Nanostructured mucoadhesive microparticles for enhanced preocular retention.
AB  - We describe nanostructured microparticles (NMs) containing a mucoadhesive polymer
      for enhanced preocular retention and consider them as potential carriers of drugs
      to the eye. These NMs are each composed of entangled nanofibers to give an
      enlarged specific surface area, and thus can better adhere to the preocular mucus
      surface. This physical design allows the microparticles still to be composed
      mainly of a wall material, poly(lactic-co-glycolic acid), as required for
      controlled drug delivery, while the effects of an additive, mucoadhesive
      material, polyethylene glycol, can be synergistically improved via the
      nanostructured morphology. Thus, when formulated in a dry tablet dosage form, the
      NMs in this work show more than a 10-fold increase in preocular retention in vivo
      compared to conventional spherical microparticles. Therefore, we conclude that
      these mucoadhesive NMs can reside on the preocular surface for a prolonged
      period, and thus appear to be a promising system for topical drug delivery to the
      eye. 

PMID- 23978410
TI  - Enzyme-accelerated and structure-guided crystallization of calcium carbonate:
      role of the carbonic anhydrase in the homologous system.
AB  - The calcareous spicules from sponges, e.g. from Sycon raphanus, are composed of
      almost pure calcium carbonate. In order to elucidate the formation of those
      structural skeletal elements, the function of the enzyme carbonic anhydrase (CA),
      isolated from this species, during the in vitro calcium carbonate-based spicule
      formation, was investigated. It is shown that the recombinant sponge CA
      substantially accelerates calcium carbonate formation in the in vitro diffusion
      assay. A stoichiometric calculation revealed that the turnover rate of the sponge
      CA during the calcification process amounts to 25 CO2s(-1) * molecule CA(-1).
      During this enzymatically driven process, initially pat-like particles are formed
      that are subsequently transformed to rhomboid/rhombohedroid crystals with a
      dimension of ~50 MUm. The CA-catalyzed particles are smaller than those which are
      formed in the absence of the enzyme. The Martens hardness of the particles formed
      is ~4 GPa, a value which had been determined for other biogenic calcites. This
      conclusion is corroborated by energy-dispersive X-ray spectroscopy, which
      revealed that the particles synthesized are composed predominantly of the
      elements calcium, oxygen and carbon. Surprising was the finding, obtained by
      light and scanning electron microscopy, that the newly formed calcitic crystals
      associate with the calcareous spicules from S. raphanus in a highly ordered
      manner; the calcitic crystals almost perfectly arrange in an array orientation
      along the two opposing planes of the spicules, leaving the other two plane arrays
      uncovered. It is concluded that the CA is a key enzyme controlling the calcium
      carbonate biomineralization process, which directs the newly formed particles to
      existing calcareous spicular structures. It is expected that with the given tools
      new bioinspired materials can be fabricated.

PMID- 23978411
TI  - Multiscale relationships between fibronectin structure and functional properties.
AB  - Cell behavior is tightly coupled to the properties of the extracellular matrix
      (ECM) to which they attach. Fibronectin (Fn) forms a supermolecular, fibrillar
      component of the ECM that is prominent during development, wound healing and the
      progression of numerous diseases. This indicates that Fn has an important
      function in controlling cell behavior during dynamic events in vivo. The
      multiscale architecture of Fn molecules assembled into these fibers determines
      the ligand density of cell adhesion sites on the surface of the Fn fiber, Fn
      fiber porosity for cell signaling molecules such as growth factors, the
      mechanical stiffness of the Fn matrix and the adhesivity of Fn for its numerous
      soluble ligands. These parameters are altered by mechanical strain applied to the
      ECM. Recent efforts have attempted to link the molecular properties of Fn with
      bulk properties of Fn matrix fibers. Studies of isolated Fn fibers have helped to
      characterize the fiber's material properties and, in combination with models of
      Fn molecular behavior in the fibers, have begun to provide insights into the Fn
      molecular arrangement and intermolecular adhesions within the fibers. A review of
      these studies allows the development of an understanding of the mechanobiological
      functions of Fn. 

PMID- 23978412
TI  - Coprophilous fungi: antibiotic discovery and functions in an underexplored arena
      of microbial defensive mutualism.
AB  - Microbial antibiotics can mediate mutualisms and interorganism communications.
      Herbivorous animal dung offers opportunities for discovery of new antibiotics
      from microbial communities that compete for a nutrient-rich, ephemeral resource.
      Distinct lineages form a specialized community of coprophilous (dung-colonizing)
      fungi. Bacteria, protists, invertebrates, the mammalian digestive system, and
      other fungi can pose challenges to their fitness in the dung environment. The
      well-characterized diversity of dung fungi offers accessible systems for
      dissecting the function of antibiotics and for exploring fungal genomes for new
      antibiotics. Their potential for antibiotic discovery is evidenced by a high
      frequency of antifungal antibiotics and bioactive secondary metabolites from
      limited prior efforts and from mapping biosynthetic pathways in the genomes of
      the coprophilous fungi Podospora anserina and Sordaria macrospora. 

PMID- 23978413
TI  - Impact of exercise training on redox signaling in cardiovascular diseases.
AB  - Reactive oxygen and nitrogen species regulate a wide array of signaling pathways
      that governs cardiovascular physiology. However, oxidant stress resulting from
      disrupted redox signaling has an adverse impact on the pathogenesis and
      progression of cardiovascular diseases. In this review, we address how redox
      signaling and oxidant stress affect the pathophysiology of cardiovascular
      diseases such as ischemia-reperfusion injury, hypertension and heart failure. We
      also summarize the benefits of exercise training in tackling the hyperactivation
      of cellular oxidases and mitochondrial dysfunction seen in cardiovascular
      diseases. 

PMID- 23978414
TI  - Resveratrol modulates autophagy and NF-kappaB activity in a murine model for
      treating non-alcoholic fatty liver disease.
AB  - In this study, we aimed to investigate the therapeutic effects and involved
      mechanisms of resveratrol on an established non-alcoholic fatty liver disease
      (NAFLD) murine model. Wild-type and autophagic mediator ULK1 heterozygous
      knockout mice were induced to have NAFLD by high-fat diet for 8weeks. After that,
      resveratrol treatment was applied with the high-fat diet feeding for another
      4weeks. Typical features of NAFLD, including histological changes, fibrosis,
      insulin resistance, oxidative status, and inflammation were characterized. After
      treatment with resveratrol showed ameliorative effects on all measured features
      of NAFLD, from histology, insulin resistance, glucose tolerance to oxidative
      stress and inflammation. resveratrol treatment also reduced the activity of
      nuclear factor-kappaB (NF-kappaB) through the restoration of its inhibitor
      IkappaBalpha. Partial inhibition of ULK1 expression impaired the ameliorative
      effects of resveratrol on hepatic histology, fibrosis, oxidative status,
      inflammation, and NF-kappaB activity. In conclusion, resveratrol improved NAFLD
      caused hepatic injury partially through regulating autophagic and IkappaBalpha-NF
      kappaB pathways. 

PMID- 23978415
TI  - Effects of Al on the splenic immune function and NE in rats.
AB  - Norepinephrine (NE) regulates the splenic immune function and it may be related
      to the effects of Aluminum (Al) on the splenic immune function. Here, the aim of
      this study was to further explore the effects of aluminum trichloride (AlCl3) on
      the splenic immune function and its relationship with NE. Forty male Wistar rats
      were orally exposed to AlCl3 (0, 64.18, 128.36 and 256.72 mg/kg BW) through
      drinking water for 120 days. The CD3(+), CD4(+), CD8(+) T lymphocytes, the T and
      B lymphocytes proliferation rates and serum NE concentration were examined. The
      correlation analysis between splenic immune function and NE were done. The
      results showed that the CD3(+), CD4(+), CD8(+) T lymphocytes and the T and B
      lymphocytes proliferation rates decreased and NE concentration increased in AlCl3
      treated rats. NE was negatively correlated with proportions of CD3(+), CD4(+) T
      lymphocytes and T and B lymphocytes proliferation rates, but not correlated with
      CD8(+) T lymphocytes. The results suggest that AlCl3 suppresses the splenic
      immune function and NE plays important role in this process.

PMID- 23978416
TI  - Curcumin analogue identified as hyaluronan export inhibitor by virtual docking to
      the ABC transporter MRP5.
AB  - Hyaluronan is overproduced in many diseases including metastasis, inflammation or
      ischemia, but there is no drug to attenuate hyaluronan production. Hyaluronan is
      exported from fibroblasts by the multidrug resistance associated protein 5 (MRP5)
      which is inhibited by the plant phenols curcumin or xanthohumol. We performed
      virtual docking and chemical synthesis of analogues to optimize the inhibitors.
      The AutoDock software was used to identify the binding cavity within the open
      conformation of MRP5. Inhibitory plant phenols bound to the ATP binding site
      between the two nucleotide binding domains NBD1 and NBD2. This binding cavity was
      chosen to screen about 120 derivatives and analogues. The superior hyaluronan
      export inhibitor was 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one
      (hylin). It inhibited hyaluronan export from fibroblasts with an IC50 of 4.9 MUM.
      Hylin is a minor component in natural curcumin preparations and has previously
      been described as anti-metastatic and anti-inflammatory. Since curcumin itself is
      unstable under physiological conditions, the active component for many cell
      biological and pharmaceutical effects of natural curcumin preparations could be
      hylin that acts by hyaluronan export inhibition.

PMID- 23978417
TI  - Match performance and physical capacity of players in the top three competitive
      standards of English professional soccer.
AB  - The aim of this study was to compare the match performance and physical capacity
      of players in the top three competitive standards of English soccer. Match
      performance data were collected from players in the FA Premier League (n=190),
      Championship (n=155) and League 1 (n=366) using a multiple-camera system. In
      addition, a selection of players from the Premier League (n=56), Championship
      (n=61) and League 1 (n=32) performed the Yo-Yo intermittent endurance test level
      2 (Yo-Yo IE2) to determine physical capacity. Players in League 1 and the
      Championship performed more (p<.01) high-intensity running than those in the
      Premier League (Effect Size [ES]: 0.4-1.0). Technical indicators such as pass
      completion, frequency of forward and total passes, balls received and average
      touches per possession were 4-39% higher (p<.01) in the Premier League compared
      to lower standards (ES: 0.3-0.6). Players also covered more (p<.05) high
      intensity running when moving down (n=20) from the Premier League to the
      Championship (ES: 0.4) but not when players moved up (n=18) standards (ES: 0.2).
      Similar Yo-Yo IE2 test performances were observed in Premier League, Championship
      and League 1 players (ES: 0.2-0.3). Large magnitude relationships (p<.05) were
      observed between Yo-Yo IE2 test performances and the total and high-intensity
      running distance covered in both Championship (r=.56 and .64) and Premier League
      matches (r=.61 and .54). The data demonstrate that high-intensity running
      distance was greater in players at lower compared to higher competitive standards
      despite a similar physical capacity in a subsample of players in each standard.
      These findings could be associated with technical characteristics inherent to
      lower standards that require players to tax their physical capacity to a greater
      extent but additional research is still required to confirm these findings. 

PMID- 23978418
TI  - Breast cancer cell behaviors on staged tumorigenesis-mimicking matrices derived
      from tumor cells at various malignant stages.
AB  - Extracellular matrix (ECM) has been focused to understand tumor progression in
      addition to the genetic mutation of cancer cells. Here, we prepared "staged
      tumorigenesis-mimicking matrices" which mimic in vivo ECM in tumor tissue at each
      malignant stage to understand the roles of ECM in tumor progression. Breast tumor
      cells, MDA-MB-231 (invasive), MCF-7 (non-invasive), and MCF-10A (benign) cells,
      were cultured to form their own ECM beneath the cells and formed ECM was prepared
      as staged tumorigenesis-mimicking matrices by decellularization treatment. Cells
      showed weak attachment on the matrices derived from MDA-MB-231 cancer cells. The
      proliferations of MDA-MB-231 and MCF-7 was promoted on the matrices derived from
      MDA-MB-231 cancer cells whereas MCF-10A cell proliferation was not promoted. MCF
      10A cell proliferation was promoted on the matrices derived from MCF-10A cells.
      Chemoresistance of MDA-MB-231 cells against 5-fluorouracil increased on only
      matrices derived from MDA-MB-231 cells. Our results showed that the cells showed
      different behaviors on staged tumorigenesis-mimicking matrices according to the
      malignancy of cell sources for ECM preparation. Therefore, staged tumorigenesis
      mimicking matrices might be a useful in vitro ECM models to investigate the roles
      of ECM in tumor progression. 

PMID- 23978419
TI  - Association of plasma C-reactive protein levels with the diagnosis of Alzheimer's
      disease.
AB  - C-reactive protein (CRP) participates in the systemic response to inflammation.
      Previous studies report inconsistent findings regarding the relationship between
      plasma CRP and Alzheimer's disease (AD). We measured plasma CRP in 203 subjects
      with AD, 58 subjects with mild cognitive impairment (MCI) and 117 normal aging
      subjects and administered annual Mini-Mental State Examinations (MMSE) during a 3
      year follow-up period to investigate CRP's relationship with diagnosis and
      progression of cognitive decline. Adjusted for age, sex, and education, subjects
      with AD had significantly lower levels of plasma CRP than subjects with MCI and
      normal aging. However, there was no significant association between plasma CRP at
      baseline and subsequent cognitive decline as assessed by longitudinal changes in
      MMSE score. Our results support previous reports of reduced levels of plasma CRP
      in AD and indicate its potential utility as a biomarker for the diagnosis of AD. 

PMID- 23978420
TI  - The number of independent variables and events for multiple logistic regression
      analysis.

PMID- 23978421
TI  - Determinants of mismatch in acute ischaemic stroke.
AB  - BACKGROUND: Multimodal CT or MR imaging may be helpful in guiding reperfusion
      therapy for stroke. However, access to multimodal imaging may frequently be
      limited. We hypothesised that certain clinical and non-enhanced CT (NECT)
      findings at initial assessment can potentially predict mismatch on CT perfusion
      (CTP) in patients with acute ischaemic stroke. METHODS: We undertook an analysis
      of prospectively collected clinical and imaging data of consecutive patients with
      anterior circulation ischaemic stroke who underwent CTP during their initial
      assessment. NECT was read for early ischaemic change as measured by the Alberta
      Stroke Program Early CT Score (ASPECTS), and for hyperdense middle cerebral
      artery sign (HMCAS). CTP images were evaluated for mismatch. Independent clinical
      and imaging predictors of a CTP mismatch were identified using stepwise logistic
      regression. RESULTS: Of the 202 patients, 92 (46%) demonstrated a mismatch, 23
      (11%) a matched deficit, and 87 (43%) no perfusion deficit. HMCAS on NECT (OR
      13.65, 95% CI 6.04-30.81, p<0.001), female gender (OR 2.37, 95% CI 1.19-4.72, p =
      0.015), atrial fibrillation (OR 2.05, 95% CI 1.02-4.11, p = 0.044), and absence
      of a history of hypertension (OR 0.46, 95% CI 0.22-0.96, p = 0.037) were
      independent predictors of a CTP mismatch. HMCAS had 58% sensitivity, 91%
      specificity, 84% positive predictive value and 72% negative predictive value.
      CONCLUSIONS: A HMCAS on the initial NECT is associated with a high probability of
      mismatch in acute ischaemic stroke, and may identify patients most likely to
      benefit from recanalisation treatments when access to multimodal CT or MR
      facilities is limited.

PMID- 23978422
TI  - Patterns of neuropsychological impairment in Alzheimer's disease and mixed
      dementia.
AB  - BACKGROUND: Mixed dementia (MD), i.e., the coexistence of Alzheimer's disease
      (AD) and cerebrovascular disease (CVD), is a common dementia subtype. Few studies
      have attempted to establish the cognitive profiles of mild-moderate MD and
      compare it to the profiles of AD using a comprehensive neuropsychological test
      battery. We aimed to establish the neuropsychological profile of mild-moderate MD
      in relation to mild-moderate AD. METHODS: Patients with consensus diagnoses of MD
      and AD of mild-moderate severity (Clinical Dementia Rating score of 1-2) were
      recruited from a memory clinic. Cognitive performance was measured by a formal
      neuropsychological battery covering domains of attention, language, verbal and
      visual memory, visuoconstruction, visuomotor speed and executive function.
      Cognitive domain scores are z-scores calculated using the mean and SDs of the AD
      group. ANCOVAs with age and education as covariates were employed to examine
      differences in mean score difference of cognitive domains and subtests between
      patients with MD and AD. RESULTS: 151 patients were recruited with the majority
      of AD (n=96, 63.6%) and a minority of MD (n=55, 36.4%). There were no significant
      differences in the demographic characteristics of patients with MD and AD.
      However, patients with MD were significantly more impaired than AD patients in
      global cognitive composite, attention and visuoconstruction (global cognitive
      composite: -0.32+/-0.98 vs 0+/-1, p=0.011; attention: -0.32+/-0.90 vs 0+/-1,
      p=0.013; visuoconstruction: -0.27+/-0.99 vs 0+/-1, p=0.024, respectively).
      CONCLUSION: The neuropsychological profile of patients with MD of mild-moderate
      severity is characterized by a poorer global performance, as well as attention
      and visuoconstruction than those with AD of mild-moderate severity.

PMID- 23978423
TI  - Usefulness of breast-conserving surgery using the round block technique or
      modified round block technique in Japanese females.
AB  - BACKGROUND: The round block technique (RBT) is an oncoplastic technique in which
      only the perimamillary scars remain visible. We have performed RBT in cases that
      require resection of the breast tissue under the nipple-areola complex (NAC) and
      a modified round block technique (MRBT) in peripheral cases in which performing
      resection of the breast tissue under the NAC is unnecessary. We herein report the
      usefulness of these techniques. METHODS: The study participants consisted of 18
      patients who underwent breast-conserving surgery (BCS) using MRBT or RBT between
      July 2010 and July 2011. In the cases using RBT, de-epithelialization between the
      outer and inner incision lines was performed and the dermis was cut at the side
      of the tumor location. For MRBT cases, the dermis was cut in all parts of the
      inner and outer circles, and the skin between the inner and outer incision lines
      was resected. RESULTS: Cosmetic results were found to be excellent in three
      cases, good in eight cases, fair in five cases, and poor in two cases. In this
      study, the cosmetic results were unacceptable (fair and poor) in patients who
      underwent >=25% resection or in whom the resected area was part of the lower
      portion of the breast. CONCLUSION: These techniques are useful for performing BCS
      in the upper portion of the breast. However, if the excision volume is >20% or
      excision of part of the lower portion of the breast is required, other procedures
      should be considered.

PMID- 23978424
TI  - Vacuum-assisted closure therapy for salvaging a methicillin-resistant
      Staphylococcus aureus-infected prosthetic graft.
AB  - Infection of a vascular prosthesis after a bypass surgery is relatively rare.
      However, once developed, serious complications can occur, such as bleeding,
      sepsis, and organ ischemia, occasionally resulting in leg amputation or even
      death in some cases. The treatment of a vascular prosthesis infection involves
      the necessary removal of the infected graft; subsequently, an extra-anatomical
      bypass surgery is often considered. We herein report a case in which
      postoperative methicillin-resistant Staphylococcus aureus infection caused
      dehiscence of the femoral vessels and exposure of the graft vessel and
      anastomosed area. The infected tissue was surgically removed (debridement), and
      the patient's condition was successfully treated by the application of a
      nonadherent dressing and vacuum-assisted closure therapy combined with the
      bridging technique. 

PMID- 23978425
TI  - Anastomotic stability and wound healing of colorectal anastomoses sealed and
      sutured with a collagen fleece in a rat peritonitis model.
AB  - BACKGROUND/OBJECTIVE: Anastomotic insufficiency is associated with increased
      morbidity and mortality. A collagen fleece that supports anastomosis is effective
      for preventing anastomosis insufficiency. The objective of this study was to
      compare between the stability of sutured anastomoses and that of anastomoses
      sealed with a thrombin/fibrinogen-coated collagen fleece in a rat peritonitis
      model. METHODS: In 72 male Wistar rats, peritonitis was induced with a specially
      prepared human fecal solution. Surgery at the rectosigmoid junction was performed
      24-36 hours later. The different anastomotic techniques used were circular
      sutured anastomoses, semicircular sutured anastomosis and closure of the anterior
      wall with collagen patch, and complete closure with a collagen fleece. Bursting
      pressure, histology of anastomosis, mRNA expression of collagen types I and III,
      matrix metalloproteinase-13, and vascular endothelial growth factor (VEGF) were
      investigated after 24 hours, 72 hours, and 120 hours. RESULTS: All animals
      developed peritonitis of comparable severity. There were no differences in
      bursting pressures between the three suture techniques after 24 hours, 72 hours,
      or 120 hours. Anastomoses sealed with a collagen fleece appeared to be slightly
      less stable only at 24 hours, whereas they appeared to be more stable than
      semisutured or fully sutured anastomoses at 72 hours and 120 hours. Sealing with
      a collagen fleece was associated with an increase in granulation tissue, higher
      mRNA levels for collagen types I and III, and higher VEGF compared to sutured
      anastomoses. CONCLUSION: The use of a thrombin/fibrinogen-coated collagen fleece
      showed similar efficacy to conventional sutures in colorectal anastomoses in the
      presence of peritonitis inflammation, and may provide additional benefits due to
      an increase in mature granulation tissue.

PMID- 23978426
TI  - Pseudolymphoma of the liver: Report of a case and review of the literature.
AB  - We report a case of pseudolymphoma of the liver in a 49-year-old woman without an
      underlying disease except for liver hemangioma. A 20-mm nodule was incidentally
      found in segment 2 of the liver by abdominal ultrasonography during a regular
      follow-up of the hepatic hemangioma. After a series of radiological examinations,
      a left lateral sectionectomy was performed because malignant hepatic tumor could
      not be excluded. The patient was discharged uneventfully 7 days after the
      operation. The pathology examination revealed a pseudolymphoma. No recurrence of
      the tumor was found 51/2 years after the operation. To the best of our knowledge,
      only 46 cases of pseudolymphoma of the liver have been reported to date. A review
      of the literature showed that pseudolymphomas occur predominantly in females
      (89.4%), usually occur as a single tumor (80.4%), are no more than 20 mm in size
      (90.6%), and are frequently associated with either autoimmune disease or chronic
      liver disease. Because an accurate diagnosis is difficult to establish, vigilant
      follow-up is indicated, and surgical intervention is the choice of treatment once
      the suspiciousness of malignancy has been raised.

PMID- 23978427
TI  - Adventitial cystic disease of the common femoral vein presenting as deep vein
      thrombosis.
AB  - Adventitial cystic disease of the common femoral vein is a rare condition. We
      herein report the case of a 50-year-old woman who presented with painless
      swelling in her left lower leg that resembled deep vein thrombosis. She underwent
      femoral exploration and excision of the cystic wall. The presentation,
      investigation, treatment, and pathology of this condition are discussed with a
      literature review. 

PMID- 23978428
TI  - An unusual cause of acute abdomen-Gas-forming liver abscess due to Salmonella
      enteritidis.
AB  - Gas-forming pyogenic liver abscess (GFPLA) is considered to be a very severe form
      of PLA and carries a high mortality. Klebsiella pneumoniae is the most common
      pathogen responsible for the disease, whereas cases where Salmonella is cited as
      the cause are very uncommon. We report the first case of a 53-year-old lady
      suffering from GFPLA due to Salmonella, who was successfully treated with
      surgical drainage. To the best of our knowledge, this is the first case of GFPLA
      caused by Salmonella enteritidis to be reported in the English literature.

PMID- 23978429
TI  - Pseudoaneurysm after sutureless repair of left ventricular free wall rupture:
      Sequential magnetic resonance imaging demonstration.
AB  - Sutureless repair is an effective procedure for acute left ventricular free wall
      rupture; however, it may be complicated with a left ventricular pseudoaneurysm
      during the late postoperative period. We present a case of a large ventricular
      pseudoaneurysm that occurred after the sutureless repair of an inferior
      myocardial infarction with oozing left ventricular free wall rupture. The patient
      underwent aneurysmectomy successfully. Serial magnetic resonance imaging (MRI)
      indicated that the necrotic left ventricular wall, which was covered by Teflon
      felt, had ruptured and developed a pseudoaneurysm. Therefore, after simple gluing
      for a left ventricular free wall rupture, patients should undergo careful follow
      up evaluation for potential pseudoaneurysm. Moreover, early detection by MRI and
      prompt surgical repair of the complication are important in patients with left
      ventricular free wall rupture. 

PMID- 23978430
TI  - Lipomatous ganglioneuroma of the retroperitoneum.
AB  - Lipomatous ganglioneuroma (LG) is a rare variant of ganglioneuroma that is
      histologically characterized by a mature adipocytic component admixed with a
      conventional ganglioneuroma. We report the clinicopathological and
      immunohistochemical features of an LG in a 44-year-old Chinese male;
      additionally, we review the literature regarding this type of tumor. Magnetic
      resonance imaging revealed a left paravertebral soft-tissue mass at the T11-L3
      levels. Grossly, the encapsulated neoplasm had a white to yellowish cut surface
      and rubbery consistency. Microscopic evaluation revealed an encapsulated lesion
      that consisted of areas of ganglioneuroma admixed with areas of mature fat. By
      immunohistochemistry, the ganglion cells were positive for chromogranin and
      synaptophysin, whereas the Schwann cells were positive for vimentin, S-100
      protein, and glial fibrillary acidic protein (GFAP). This is the second known
      report of a retroperitoneal LG. The patient was well and without evidence of
      disease at 2 years' follow-up. 

PMID- 23978431
TI  - Comparison of the Nuss and sternal turnover procedures for primary repair of
      pectus excavatum.
AB  - BACKGROUND: Pectus excavatum (PE) is a common chest wall deformity. There are
      several surgical alternatives for the repair of PE. In our practice, the sternal
      turnover (STO) procedure had been performed for decades. In 2008, we started
      treating PE patients with the Nuss procedure. Our objective of this study is to
      compare these two procedures. METHODS: A retrospective chart review was conducted
      on 50 patients undergoing pectus excavatum repairs from March 2005 to January
      2013, including 20 patients with the STO procedure and 30 patients with the Nuss
      procedure. Patients were evaluated for type of repair performed, operating time,
      drainage after operation, length of postoperative stay, complications, and
      cosmetic results. RESULTS: The mean age of the STO group was 11.0 years and that
      of the Nuss group was 15.0 years (p = 0.353). The Nuss procedure had a much
      shorter mean operating time, a less mean drainage after operation, and a shorter
      mean time to drainage tube removal than those of the STO procedure. The rate of
      complication was 40.0% (8/20) in the STO group and 33.3% (10/30) in the Nuss
      group. Follow-up data indicated that 90% (18/20) of patients in the STO group and
      96.7% (29/30) of patients in the Nuss group regarded the results as good or
      excellent (p = 0.965). CONCLUSION: Our data suggests that both the STO and Nuss
      procedures are equally safe and effective correction methods. However, less
      trauma, faster recovery, and better cosmetic results are the benefits of the Nuss
      procedure.

PMID- 23978432
TI  - Meningeal seeding from glioblastoma multiforme treated with radiotherapy and
      temozolomide.
AB  - Extracranial and meningeal seeding of glioblastoma multiforme is rare. We report
      herein a case of glioblastoma in a 41-year-old man who underwent surgical
      resection, concomitant chemoradiotherapy (CCRT) and seven courses of adjuvant
      chemotherapy with temozolomide. The patient then complained of intermittent
      severe lower back pain and gait disturbance. Imaging studies demonstrated that
      although the intracranial residual tumors were well-controlled by the treatment,
      meningeal seeding involving the brainstem and spinal cord was present. The
      patient died 2 months after the diagnosis of spinal seeding. This case
      illustrates the need for consideration of extracranial metastasis if a patient is
      symptomatic, even if the intracranial tumor appears responsive to treatment. We
      suggested that the prophylactic craniospinal irradiation may be considered in
      patients at high risk of meningeal seeding immediately after surgery.

PMID- 23978434
TI  - Hepatocellular carcinoma vascularization: from the most common to the lesser
      known arteries.
AB  - Hepatocellular carcinoma is the sixth most common cancer throughout the world. It
      is almost exclusively arterially vascularized, unlike the vascularization of the
      liver, which has a dual supply with a portal component of 75 to 80% and an
      arterial component of 20 to 25%. The reference treatment for intermediary stages
      of the Barcelona (B) classification is hepatic artery chemoembolization. The aim
      of chemoembolization is to inject the tumor chemotherapy into the artery and then
      to embolize the artery (or arteries), which supply the tumor. For this, knowledge
      of the anatomy of the hepatic artery is essential. Approximately 55% of the
      patients belong to the modal distribution, although numerous anatomical variants
      exist and must be recognized. In addition, primarily non-hepatic arteries may
      contribute to the vascularization of some hepatocellular carcinomas. Furthermore,
      new arterial supplies can be recruited by tumors after surgical or
      chemoembolization treatments. The aim of this article is to describe the
      different arteries, which may vascularize hepatocellular carcinomas. These
      arteries must be looked for, recognized, and reported by the radiologist on cross
      section examinations in the pre-treatment assessment. 

PMID- 23978435
TI  - Rare complication: what kind of colitis?

PMID- 23978436
TI  - New-onset gastrointestinal polyposis.

PMID- 23978437
TI  - A rare cause of gastrointestinal bleeding in a young man.

PMID- 23978438
TI  - The egg-planted omentum.

PMID- 23978439
TI  - The rapid rise in gastroesophageal junction tumors: is inflammation of the
      gastric cardia the underwater iceberg?

PMID- 23978440
TI  - A rare cause of epigastric pain and vomiting.

PMID- 23978441
TI  - A problematic polyp.

PMID- 23978442
TI  - Results from early therapy with azathioprine in Crohn's disease.

PMID- 23978444
TI  - Will the real inner-city allergen please stand up?

PMID- 23978443
TI  - Maternal and cord blood miR-223 expression associates with prenatal tobacco smoke
      exposure and low regulatory T-cell numbers.
AB  - BACKGROUND: There is evidence that microRNAs (miRNAs) are sensitive to
      environmental stressors, including tobacco smoke. On the other hand, miRNAs are
      involved in immune regulation, such as regulatory T (Treg) cell differentiation.
      The aim of the present study was to investigate the association between prenatal
      tobacco smoke exposure, miRNAs, and Treg cell numbers. METHODS: Within a
      prospective mother-child study (Lifestyle and Environmental Factors and Their
      Influence on Newborns Allergy Risk), we analyzed the expression of miR-155 and
      miR-223 together with Treg cell numbers in maternal blood during pregnancy, as
      well as in cord blood (n = 441). Tobacco smoke exposure was assessed based on
      questionnaire answers and maternal urine cotinine levels. Additionally, the
      concentration of smoking-related volatile organic compounds was measured in
      dwellings of study participants. RESULTS: Both maternal and cord blood miR-223
      expressions were positively correlated with maternal urine cotinine levels. An
      association was also found between maternal miR-223 expression and indoor
      concentrations of benzene and toluene. High miR-223 expression was associated
      with lower Treg cell numbers in maternal and cord blood. Furthermore, children
      with lower Treg cell numbers at birth had a higher risk of atopic dermatitis
      during the first 3 years of life. The concentration of the toluene metabolite S
      benzylmercapturic acid in maternal urine was associated with decreased cord
      blood, but not maternal blood, miR-155 expression. A relationship between miR-155
      expression and Treg cell numbers was not found. CONCLUSIONS: For the first time,
      we show that maternal tobacco smoke exposure during pregnancy correlates with the
      level of miRNA-223 expression in blood, with an effect on children's cord blood
      Treg cell numbers and subsequent allergy risk.

PMID- 23978445
TI  - Ethanol increases matrix metalloproteinase-12 expression via NADPH oxidase
      dependent ROS production in macrophages.
AB  - Matrix metalloproteinase-12 (MMP-12), an enzyme responsible for degradation of
      extracellular matrix, plays an important role in the progression of various
      diseases, including inflammation and fibrosis. Although most of those are
      pathogenic conditions induced by ethanol ingestion, the effect of ethanol on MMP
      12 has not been explored. In the present study, we investigated the effect of
      ethanol on MMP-12 expression and its potential mechanisms in macrophages. Here,
      we demonstrated that ethanol treatment increased MMP-12 expression in primary
      murine peritoneal macrophages and RAW 264.7 macrophages at both mRNA and protein
      levels. Ethanol treatment also significantly increased the activity of
      nicotinamide adenine dinucleotide (NADPH) oxidase and the expression of NADPH
      oxidase-2 (Nox2). Pretreatment with an anti-oxidant (N-acetyl cysteine) or a
      selective inhibitor of NADPH oxidase (diphenyleneiodonium chloride (DPI))
      prevented ethanol-induced MMP-12 expression. Furthermore, knockdown of Nox2 by
      small interfering RNA (siRNA) prevented ethanol-induced ROS production and MMP-12
      expression in RAW 264.7 macrophages, indicating a critical role for Nox2 in
      ethanol-induced intracellular ROS production and MMP-12 expression in
      macrophages. We also showed that ethanol-induced Nox2 expression was suppressed
      by transient transfection with dominant negative IkappaB-alpha plasmid or
      pretreatment with Bay 11-7082, a selective inhibitor of NF-kappaB, in RAW 264.7
      macrophages. In addition, ethanol-induced Nox2 expression was also attenuated by
      treatment with a selective inhibitor of p38 MAPK, suggesting involvement of p38
      MAPK/NF-kappaB pathway in ethanol-induced Nox2 expression. Taken together, these
      results demonstrate that ethanol treatment elicited increase in MMP-12 expression
      via increase in ROS production derived from Nox2 in macrophages. 

PMID- 23978446
TI  - Fast metabolic response to drug intervention through analysis on a miniaturized,
      highly integrated molecular imaging system.
AB  - We report on a radiopharmaceutical imaging platform designed to capture the
      kinetics of cellular responses to drugs. METHODS: A portable in vitro molecular
      imaging system comprising a microchip and a beta-particle imaging camera
      permitted routine cell-based radioassays of small numbers of either suspended or
      adherent cells. We investigated the kinetics of responses of model lymphoma and
      glioblastoma cancer cell lines to (18)F-FDG uptake after drug exposure. Those
      responses were correlated with kinetic changes in the cell cycle or with changes
      in receptor tyrosine kinase signaling. RESULTS: The platform enabled direct
      radioassays of multiple cell types and yielded results comparable to those from
      conventional approaches; however, the platform used smaller sample sizes,
      permitted a higher level of quantitation, and did not require cell lysis.
      CONCLUSION: The kinetic analysis enabled by the platform provided a rapid (~ 1 h)
      drug screening assay.

PMID- 23978447
TI  - A PET-compatible tissue bioreactor for research, discovery, and validation of
      imaging biomarkers and radiopharmaceuticals: system design and proof-of-concept
      studies.
AB  - Research and discovery of novel radiopharmaceuticals and targets thereof
      generally involves initial studies in cell cultures, followed by animal studies,
      both of which present several inherent limitations. The objective of this work
      was to develop a tissue bioreactor (TBR) enabling modulation of the
      microenvironment and to integrate the TBR with a small-animal PET scanner to
      facilitate imaging biomarker research and discovery and validation of
      radiopharmaceuticals. METHODS: The TBR chamber is a custom-blown, water-jacketed,
      glass vessel enclosed in a circulating perfusion bath powered by a peristaltic
      pump, which is integrated within the field of view of the PET scanner. The
      chamber is in series with a gas exchanger and a vessel for degassing the system
      during filling. Dissolved oxygen/temperature probes and septa for injection or
      sampling are located at the inlet and outlet of the cell chamber. A pH probe is
      located at the chamber outlet. Effluent is collected in the fraction collector as
      mixed-cup samples. In addition, both medium and tissue chamber can be sampled to
      investigate tissue and secretory products through multiscale analysis. As a proof
      of concept, we studied the effects of lipids on glucose uptake using HepG2 cells.
      To that end, we varied the nutrient substrate environment over a period of
      approximately 27 d, before and after the addition of lipids, and studied the
      effects of pioglitazone, a peroxisome proliferator-activated receptor gamma
      agonist, on lipid and glucose uptake. In parallel, the TBR was imaged by PET in
      conjunction with (11)C-palmitate in the presence and absence of lipids to
      characterize (11)C-palmitate uptake. RESULTS: The O2 consumption, glucose
      consumption, lactate production, and free fatty acid consumption and production
      rates were consistent in demonstrating the effects of lipids on glucose uptake.
      Pioglitazone exhibited improved glucose uptake within 3 d of treatment.
      Semiquantitative analysis suggested that lipids induced greater (11)C-palmitate
      uptake. CONCLUSION: The integrated TBR offers a platform to monitor and modulate
      the tissue microenvironment, thus facilitating tissue-specific imaging and
      therapeutic biomarkers of disease, identification of molecular diagnostic
      markers, and validation of radiopharmaceuticals in both rodent and human cell
      lines.

PMID- 23978448
TI  - An abundant LEA protein in the anhydrobiotic midge, PvLEA4, acts as a molecular
      shield by limiting growth of aggregating protein particles.
AB  - LEA proteins are found in anhydrobiotes and are thought to be associated with the
      acquisition of desiccation tolerance. The sleeping chironomid Polypedilum
      vanderplanki, which can survive in an almost completely desiccated state
      throughout the larval stage, accumulates LEA proteins in response to desiccation
      and high salinity conditions. However, the biochemical functions of these
      proteins remain unclear. Here, we report the characterization of a novel
      chironomid LEA protein, PvLEA4, which is the most highly accumulated LEA protein
      in desiccated larvae. Cytoplasmic-soluble PvLEA4 showed many typical
      characteristics of group 3 LEA proteins (G3LEAs), such as desiccation-inducible
      accumulation, high hydrophilicity, folding into alpha-helices on drying, and the
      ability to reduce aggregation of dehydration-sensitive proteins. This last
      property of LEA proteins has been termed molecular shield function. To further
      investigate the molecular shield activity of PvLEA4, we introduced two distinct
      methods, turbidity measurement and dynamic light scattering (DLS). Turbidity
      measurements demonstrated that both PvLEA4, and BSA as a positive control,
      reduced aggregation in alpha-casein subjected to desiccation and rehydration.
      However, DLS experiments showed that a small amount of BSA relative to alpha
      casein increased aggregate particle size, whereas PvLEA4 decreased particle size
      in a dose-dependent manner. Trehalose, which is the main heamolymph sugar in most
      insects but also a protectant as a chemical chaperone in the sleeping chironomid,
      has less effect on the limitation of aggregate formation. This analysis suggests
      that molecular shield proteins function by limiting the growth of protein
      aggregates during drying and that PvLEA4 counteracts protein aggregation in the
      desiccation-tolerant larvae of the sleeping chironomid. 

PMID- 23978449
TI  - Anthropometric characteristics of Australian junior representative rugby league
      players.
AB  - OBJECTIVES: To comprehensively describe anthropometric characteristics of
      Australian junior elite rugby league players and assess potential anthropometric
      dissimilarities between players of varying positional groups, ethnicity
      (Polynesian vs. non-Polynesian) and playing level (junior vs. professional; using
      published data from Australian professional players). DESIGN: Cross-sectional
      study. METHODS: Height, body mass, eight skinfolds, five girths and two bone
      breadths were measured with body fat (BF%) and somatotype calculated using
      population-appropriate equations. DATA: mean +/- SD. RESULTS: This study
      recruited 116 junior players. Mean age, mass and BF% were 17 +/- 1 y, 87.0 +/-
      11.6 kg and 14.0 +/- 4.6% respectively. Compared to backs, forwards had greater
      mass (92.6 +/- 12.2 vs. 80.9 +/- 7.1 kg), skinfolds, girths, femur breadth, BF%
      (16.1 +/- 4.8% vs. 11.8 +/- 3.2%) (all p<0.01), and were more endo- and
      mesomorphic, but less ectomorphic (all p<0.001). Compared to other positional
      groups, props had greater mass, adiposity, calf girth and endomorphy, while
      adjustables (fullbacks, five-eighths, halfbacks, hookers) had the shortest
      stature (all p<0.01). Polynesians exhibited greater height (181.0 +/- 5.7 vs.
      178.7 +/- 6.3 cm), mass (90.6 +/- 11.7 vs. 84.7 +/- 11.1 kg), arm and calf
      girths, bone breadths and mesomorphy (7.6 +/- 1.2 vs. 6.7 +/- 1.1) than non
      Polynesians (all p<0.05). Juniors had lower height, mass, waist and smaller sum
      of skinfolds than professional players (all p<0.05). CONCLUSIONS: Greater mass,
      mesomorphy, adiposity and bone size in forwards is desirable for tackling and
      attacking and may protect against high impact forces sustained in this position.
      Advantageous anthropometric attributes exhibited in Polynesian players may
      influence selection into junior elite rugby league teams. Anthropometric data
      from this study may assist other junior players and coaches with training,
      dietary modification and position allocation.

PMID- 23978450
TI  - Programs selection criteria for neurological surgery applicants in the United
      States: a national survey for neurological surgery program directors.
AB  - OBJECTIVES: To determine the criteria used by neurosurgery resident selection
      committees in different programs and to assess the process of selection. METHODS:
      A questionnaire based on the Electronic Residency Application Service (ERAS)
      guidelines was mailed to all 100 neurosurgery residency program directors in
      August 2011. Items included related to selection process, factors affecting
      decision, and degree of satisfaction by the process. Responses were recorded by
      the use of 4- and 3-point Likert scales of importance. Mean values were used to
      create rank orders of selection criteria. Multivariate analysis was conducted to
      determine predictors of long-term satisfaction with resident selection. RESULTS:
      The overall response rate was 46%. In the selection process the most important
      factors (>3.0) were the interview process (mean +/- SD = 3.80 +/- 0.65), United
      States Medical Licensing Examination (USMLE I) (3.58 +/- 0.54), and letters of
      recommendations (3.56 +/- 0.54). High satisfaction with selected residents was
      recorded in 60.86% of program directors. In multivariate analysis, predictors of
      long-term satisfaction with resident selection included less emphasis on letters
      of recommendation (P = 0.037) and greater weight on applicant extramural activity
      (P = 0.038). CONCLUSION: Interview process, USMLE I, and letters of
      recommendations were the most important factors affecting residents selection.
      Most of the program directors are satisfied by this process and applicants pool
      as it reflects somehow their performance during residency.

PMID- 23978433
TI  - Are hospitalized or ambulatory patients with heart failure treated in accordance
      with European Society of Cardiology guidelines? Evidence from 12,440 patients of
      the ESC Heart Failure Long-Term Registry.
AB  - AIMS: To evaluate how recommendations of European guidelines regarding
      pharmacological and non-pharmacological treatments for heart failure (HF) are
      adopted in clinical practice. METHODS AND RESULTS: The ESC-HF Long-Term Registry
      is a prospective, observational study conducted in 211 Cardiology Centres of 21
      European and Mediterranean countries, members of the European Society of
      Cardiology (ESC). From May 2011 to April 2013, a total of 12,440 patients were
      enrolled, 40.5% with acute HF and 59.5% with chronic HF. Intravenous treatments
      for acute HF were heterogeneously administered, irrespective of guideline
      recommendations. In chronic HF, with reduced EF, renin-angiotensin system (RAS)
      blockers, beta-blockers, and mineralocorticoid antagonists (MRAs) were used in
      92.2, 92.7, and 67.0% of patients, respectively. When reasons for non-adherence
      were considered, the real rate of undertreatment accounted for 3.2, 2.3, and 5.4%
      of the cases, respectively. About 30% of patients received the target dosage of
      these drugs, but a documented reason for not achieving the target dosage was
      reported in almost two-thirds of them. The more relevant reasons for non
      implantation of a device, when clinically indicated, were related to doctor
      uncertainties on the indication, patient refusal, or logistical/cost issues.
      CONCLUSION: This pan-European registry shows that, while in patients with acute
      HF, a large heterogeneity of treatments exists, drug treatment of chronic HF can
      be considered largely adherent to recommendations of current guidelines, when the
      reasons for non-adherence are taken into account. Observations regarding the real
      possibility to adhere fully to current guidelines in daily clinical practice
      should be seriously considered when clinical practice guidelines have to be
      written.

PMID- 23978451
TI  - Flaxseed enriched diet-mediated reduction in ovarian cancer severity is
      correlated to the reduction of prostaglandin E(2) in laying hen ovaries.
AB  - Prevention of ovarian cancer is the best approach for reducing the impact of this
      deadly disease. The laying hen is a robust model of spontaneous ovarian cancer
      that recapitulates the human disease. Dietary intervention with flaxseed, the
      richest vegetable source of omega-3 fatty acids (OM-3FAs) and phytoestrogen
      lignans, demonstrate the potential for effective prevention and amelioration of
      ovarian cancer by targeting inflammatory prostaglandin pathways. Prostaglandin E2
      (PGE2) is the most pro-inflammatory ecoisanoid and one of the downstream products
      of two isoforms of cyclooxygenase (COX) enzymes: COX-1 and COX-2. Our objective
      was to investigate the effect of flaxseed supplementation for one year on ovarian
      cancer and correlate its effects to expression of COX enzymes and concentrations
      of prostaglandins. White Leghorn hens were fed 10% flaxseed-enriched or standard
      diet for one year. The severity of ovarian cancer was determined by gross
      pathology and histology. COX-1 and COX-2 localization and protein and mRNA
      expression and PGE2 and PGE3 concentrations in ovaries were measured by IHC,
      western blot, quantitative real-time PCR and LC-MS-MS, respectively. The results
      demonstrated a significant reduction in late stage ovarian tumors in the flaxseed
      fed hens compared with the control diet-fed hens. In correlation with decreased
      ovarian cancer severity, concentrations of PGE2 and expression of COX-2 were
      diminished in ovaries of flaxseed-fed hens. PGE3 concentrations were below the
      level of detection. The results demonstrated that in normal ovaries, COX-1 was
      localized to the granulosa cell layer surrounding the follicles and ovarian
      surface epithelium (OSE) whereas COX-2 protein was localized to the granulosa
      cell layer in the follicle. Extensive COX-1 and COX-2 protein expression was
      found throughout the ovarian carcinoma. Our findings suggest that the flaxseed
      mediated reduction in the severity of ovarian cancer in hens is correlated to the
      reduction in PGE2 in the ovaries of flaxseed-fed hens. These findings may provide
      the basis for clinical trials of dietary intervention targeting prostaglandin
      biosynthesis for the prevention and treatment of ovarian cancer. 

PMID- 23978452
TI  - Normal range of human dietary sodium intake: a perspective based on 24-hour
      urinary sodium excretion worldwide.
AB  - BACKGROUND: The recommendation to restrict dietary sodium for management of
      hypertensive cardiovascular disease assumes that sodium intake exceeds
      physiologic need, that it can be significantly reduced, and that the reduction
      can be maintained over time. In contrast, neuroscientists have identified neural
      circuits in vertebrate animals that regulate sodium appetite within a narrow
      physiologic range. This study further validates our previous report that sodium
      intake, consistent with the neuroscience, tracks within a narrow range,
      consistent over time and across cultures. METHODS: Peer-reviewed publications
      reporting 24-hour urinary sodium excretion (UNaV) in a defined population that
      were not included in our 2009 publication were identified from the medical
      literature. These datasets were combined with those in our previous report of
      worldwide dietary sodium consumption. RESULTS: The new data included 129 surveys,
      representing 50,060 participants. The mean value and range of 24-hour UNaV in
      each of these datasets were within 1 SD of our previous estimate. The combined
      mean and normal range of sodium intake of the 129 datasets were nearly identical
      to that we previously reported (mean = 158.3+/-22.5 vs. 162.4+/-22.4 mmol/d).
      Merging the previous and new datasets (n = 190) yielded sodium consumption of
      159.4+/-22.3 mmol/d (range = 114-210 mmol/d; 2,622-4,830mg/d). CONCLUSIONS: Human
      sodium intake, as defined by 24-hour UNaV, is characterized by a narrow range
      that is remarkably reproducible over at least 5 decades and across 45 countries.
      As documented here, this range is determined by physiologic needs rather than
      environmental factors. Future guidelines should be based on this biologically
      determined range.

PMID- 23978453
TI  - AuNPs@mesoSiO2 composites for SERS detection of DTNB molecule.
AB  - A surface enhanced Raman spectroscopy (SERS) substrate made of gold nanoparticles
      embedded mesoporous silica (AuNPs@mesoSiO2) varying with size and gold
      concentrations was applied for SERS applications. In this study, the
      AuNPs@mesoSiO2 substrate produced notable intensity and more distinguishable
      peaks when compared with the spectra collected directly from an Au/Cr-coated
      substrate with regard to the detection of a lower concentration of chemicals or
      environmental contamination. Both aqueous and dried coffee rings of 5-5'-Dithio
      bis (2-nitrobenzoic acid) (DTNB) solutions were examined. SERS spectra obtained
      from the substrate showed more fingerprint peaks with significant enhancement on
      the spectra signals. The correlation between the SERS signal and the DTNB
      concentration was found to be linear within a range of 10(-2) to 10(-12) M. SERS
      enhancement between 25 and 8 times greater can be achieved for DTNB detection
      using AuNPs@mesoSiO2 compared with the normal Raman spectra obtained from the
      aqueous solution and the contact line of the dried coffee ring, respectively.

PMID- 23978454
TI  - Electrochemical immunoassay for procalcitonin antigen detection based on signal
      amplification strategy of multiple nanocomposites.
AB  - Procalcitonin, as a medium of inflammation, has become a new marker of the
      identification of severe bacterial infections in recent years and has received
      high attention due to its most ideal diagnostic indicators of specificity with
      major types of organism systemic inflammation of bacterial infection in the early
      stages. Thus, a novel method for the determination of procalcitonin (PCT) was
      developed based on a sandwich-type electrochemical immunosensor, which combined a
      simple immunosensor array as well as an effectively designed trace tag. The
      immunosensor was fabricated by layer-by-layer coating graphene (GC), carbon
      nanotubes (MWCNTs), chitosan (CS), glutaraldehyde (GA) composite on the working
      electrode, which can increase the electronic transfer rate and improve the
      surface area to capture a large number of primary antibodies (Ab1). The trace tag
      was prepared by loading high-content signal horseradish peroxidase labeled
      secondary PCT antibody (HRP-Ab2) with AuNPs, which were coated with mesoporous
      silica nanoparticles (MCM-41) through thionine linking. In comparison with
      conventional methods, the proposed immunosensor for PCT provided a better linear
      response range from 0.01 to 350 ng/mL and a lower limit of detection (LOD) of 0.5
      pg/mL under optimal experimental conditions. In addition, the immunosensor
      exhibited convenience, low cost, rapidity, good specificity, acceptable stability
      and reproducibility. Moreover, satisfactory results were obtained for the
      determination of PCT in real human serum samples, indicating that the developed
      immunoassay has the potential to find application in clinical detection of PCT
      and other tumor markers as an alternative approach.

PMID- 23978455
TI  - Efflux of monoclonal antibodies from rat brain by neonatal Fc receptor, FcRn.
AB  - Monoclonal antibody (mAb) engineering that optimizes binding to receptors present
      on brain vascular endothelial cells has enabled them to cross through the blood
      brain barrier (BBB) and access the brain parenchyma to treat neurological
      diseases. However, once in the brain the extent to which receptor-mediated
      reverse transcytosis clears mAb from the brain is unknown. The aim of this study
      was to determine the contribution of the neonatal Fc-receptor (FcRn) in rat brain
      efflux employing two different in vivo drug delivery models. Two mAb variants
      with substantially different affinities to FcRn, and no known neuronal targets,
      (IgG1 N434A and H435A) were administered to rats via intranasal-to-central
      nervous system (CNS) and intra-cranial dosing techniques. Levels of full-length
      IgG were quantified in serum and brain hemispheres by a sensitive enzyme-linked
      immunosorbent assay (ELISA). Following intra-nasal delivery, low cerebral
      hemisphere levels of variants were obtained at 20min, with a trend towards faster
      clearance of the high FcRn binder (N434A); however, the relatively higher serum
      levels confounded analysis of brain FcRn contribution to efflux. Using
      stereotaxic coordinates, we optimized the timing and dosing regimen for injection
      of mAb into the cortex. Levels of N434A, but not H435A, decreased in the cerebral
      hemispheres following bilateral injection into the rat cortex and higher levels
      of N434A were detected in serum compared to H435A after 24h. Immunohistochemical
      staining of human IgG1 in sections of cortex was consistent with these results,
      illustrating relatively less intense immunostaining in N434A than H435A dosed
      animals. Using two in vivo methods with direct cranial administration, we
      conclude that FcRn plays an important role in efflux of IgG from the rat brain. 

PMID- 23978456
TI  - Adjuvant treatments for gastric cancer: from practice guidelines to clinical
      practice.
AB  - BACKGROUND: For gastric cancers, the benefits of adjuvant radiochemotherapy and
      of perioperative chemotherapy have been demonstrated since 2001 and 2006
      respectively. The aim of this study was to evaluate the diffusion of adjuvant
      treatments in a French population. METHODS: 334 incident gastric cancers UICC
      Stage IB, II, III or IVM0 resected for cure and recorded in the Burgundy
      digestive cancer registry were retrospectively included. Patients were classified
      as having received an effective adjuvant treatment if they had been treated by
      adjuvant radiochemotherapy since 2001 or perioperative chemotherapy since 2006.
      RESULTS: The proportion of patients treated with an effective adjuvant treatment
      increased from 21.8% (2001-2005) to 40.1% (2006-2009). Patients treated in 2006
      2009 were twice as likely to receive effective adjuvant treatment as those
      treated during the period 2001-2005. During the 2004-2009 period, 62.4% of cases
      were presented in a multidisciplinary team meeting. These patients were almost
      three times more likely to receive effective adjuvant treatment than patients
      excluded from multidisciplinary team consultation. Age was a significant factor,
      independent of comorbidities. CONCLUSION: Administration of adjuvant treatment is
      still far from being considered a reference regimen in routine practice for R0
      resected gastric cancer. The increase in multidisciplinary team meetings should
      improve the situation.

PMID- 23978457
TI  - The adverse outcome pathway concept: a pragmatic tool in toxicology.
AB  - Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk
      assessment with broad potential. AOPs are designed to provide a clear-cut
      mechanistic representation of critical toxicological effects that span over
      different layers of biological organization. AOPs share a common structure
      consisting of a molecular initiating event, a series of intermediate steps and
      key events, and an adverse outcome. Development of AOPs ideally complies with
      OECD guidelines. This also holds true for AOP evaluation, which includes
      consideration of the Bradford Hill criteria for weight-of-evidence assessment and
      meeting a set of key questions defined by the OECD. Elaborate AOP frameworks have
      yet been proposed for chemical-induced skin sensitization, cholestasis, liver
      fibrosis and liver steatosis. These newly postulated AOPs can serve a number of
      ubiquitous purposes, including the establishment of (quantitative) structure
      activity relationships, the development of novel in vitro toxicity screening
      tests and the elaboration of prioritization strategies. 

PMID- 23978458
TI  - Colon preneoplasia after carcinogen exposure is enhanced and colonic serotonergic
      system is suppressed by food deprivation.
AB  - Calorie restriction regimens usually promote health and extend life-span in
      mammals. This is partially related to their preventive effects against
      malignancies. However, certain types of nutritional restriction failed to induce
      beneficial effects. The American Institute of Nutrition defines calorie
      restriction as diets which have only 40% fewer calories, but provide normal
      amounts of necessary food components such as protein, vitamins and minerals;
      whereas, food restriction means 40% less of all dietary ingredients plus 40% less
      calories. Our study aimed to test the hypothesis that the latter type of food
      deprivation (40% less food than consumed by standard fed rats) might increase
      cancer risk instead of reducing it, as is generally assumed for all dietary
      restrictive regimens. Since the endogenous modulation of the colon serotonergic
      system has been observed to play a role during the early steps of carcinogenesis
      we also investigated whether the serotoninergic system could be involved in the
      food intake modulation of cancer risk. For this, rats were exposed to a
      carcinogen and subjected to food deprivation for 56 days. Triglyceride levels and
      visceral adipose tissue were reduced while hepatic and colonic lipid peroxidation
      was increased. This dietary restriction also decreased serotonin levels in colon,
      and gene expression of its intestinal transporter and receptors. Finally, the
      numbers of preneoplastic lesions in the colon tissue of carcinogen-exposed rats
      were increased. Our data suggest that food deprivation enhances formation of
      early tumorigenic lesions by suppressing serotonergic activity in colon tissue. 

PMID- 23978459
TI  - Simvastatin-induced up-regulation of gap junctions composed of connexin 43
      sensitize Leydig tumor cells to etoposide: an involvement of PKC pathway.
AB  - Some of lipophilic statins have been reported to enhance toxicities induced by
      antineoplastic agents but the underling mechanism is unclear. The authors
      investigated the involvement of Cx43-mediated gap junction intercellular
      communication (GJIC) in the effect of simvastatin on the cellular toxicity
      induced by etoposide in this study. The results showed that a major component of
      the cytotoxicity of therapeutic levels of etoposide is mediated by gap junctions
      composed of connexin 43(Cx43) and simvastatin at the dosage which does not induce
      cytotoxicity enhances etoposide toxicity by increasing gap junction coupling. The
      augmentative effect of simvastatin on GJIC was related to the inhibition of PKC
      mediated Cx43 phosphorylation at ser368 and subsequent enhancement of Cx43
      membrane location induced by the agent. The present study suggests the
      possibility that upregulation of gap junctions may be utilized to increase the
      efficacy of anticancer chemotherapies. 

PMID- 23978460
TI  - Dose metric considerations in in vitro assays to improve quantitative in vitro-in
      vivo dose extrapolations.
AB  - Challenges to improve toxicological risk assessment to meet the demands of the EU
      chemical's legislation, REACH, and the EU 7th Amendment of the Cosmetics
      Directive have accelerated the development of non-animal based methods.
      Unfortunately, uncertainties remain surrounding the power of alternative methods
      such as in vitro assays to predict in vivo dose-response relationships, which
      impedes their use in regulatory toxicology. One issue reviewed here, is the lack
      of a well-defined dose metric for use in concentration-effect relationships
      obtained from in vitro cell assays. Traditionally, the nominal concentration has
      been used to define in vitro concentration-effect relationships. However,
      chemicals may differentially and non-specifically bind to medium constituents,
      well plate plastic and cells. They may also evaporate, degrade or be metabolized
      over the exposure period at different rates. Studies have shown that these
      processes may reduce the bioavailable and biologically effective dose of test
      chemicals in in vitro assays to levels far below their nominal concentration.
      This subsequently hampers the interpretation of in vitro data to predict and
      compare the true toxic potency of test chemicals. Therefore, this review
      discusses a number of dose metrics and their dependency on in vitro assay setup.
      Recommendations are given on when to consider alternative dose metrics instead of
      nominal concentrations, in order to reduce effect concentration variability
      between in vitro assays and between in vitro and in vivo assays in toxicology. 

PMID- 23978461
TI  - Utility of cone-beam CT imaging in prostatic artery embolization.
AB  - PURPOSE: To evaluate the utility of cone-beam computed tomography (CT) in
      patients undergoing prostatic artery (PA) embolization (PAE) for benign prostatic
      hyperplasia. MATERIALS AND METHODS: From January 2012 to January 2013, 15
      patients (age range, 59-81 y; mean, 68 y) with moderate- or severe-grade lower
      urinary tract symptoms, in whom medical management had failed were enrolled in a
      prospective United States trial to evaluate PAE. During pelvic angiography, 15
      cone-beam CT acquisitions were performed in 11 patients, and digital subtraction
      angiography was performed in all patients. Cone-beam CT images were reviewed to
      assess for sites of potential nontarget embolization that impacted therapy, a
      pattern of enhancement on cone-beam CT suggesting additional PAs, confirmation of
      prostatic parenchymal perfusion before embolization, and contralateral prostatic
      parenchymal enhancement. RESULTS: Cone-beam CT was successful in 14 of 15
      acquisitions, and PAE was successful in 14 of 15 patients (92%). Cone-beam CT
      provided information that impacted treatment in five of 11 patients (46%) by
      allowing for identification of sites of potential nontarget embolization.
      Duplicated prostatic arterial supply and contralateral perfusion were each
      identified in 21% of patients (three of 11). Prostatic perfusion was confirmed
      before embolization in 50% of acquisitions (seven of 14). CONCLUSIONS: Cone-beam
      CT is a useful technique that can potentially mitigate the risk of nontarget
      embolization. During treatment, it can allow for the interventionalist to
      identify duplicated prostatic arterial supply or contralateral perfusion, which
      may be useful when evaluating a treatment failure.

PMID- 23978462
TI  - Comparison of KRAS genotype: therascreen assay vs. LNA-mediated qPCR clamping
      assay.
AB  - BACKGROUND: Kirsten rat sarcoma virus (KRAS) wild-type status determined using a
      locked nucleic acid (LNA)-mediated quantitative polymerase chain reaction (qPCR)
      clamping assay (LNA assay) predicted response to therapy in the CRYSTAL
      (Cetuximab Combined With Irinotecan in First-Line Therapy for Metastatic
      Colorectal Cancer) study. A companion KRAS diagnostic tool has been developed for
      routine clinical use (QIAGEN therascreen kit) (QIAGEN Manchester Ltd, Manchester,
      UK). We wanted to assess the concordance between the validated US Food and Drug
      Administration (FDA)-approved therascreen assay and the LNA assay in determining
      the KRAS status of a subset of patients enrolled in the CRYSTAL study. PATIENTS
      AND METHODS: DNA extracted from paraffin-embedded tumor sections was tested for
      KRAS status using the therascreen assay. Efficacy data from the CRYSTAL study
      were assessed to determine if the overall survival (OS) hazard ratio for
      cetuximab in patients identified as having KRAS wild-type status using the
      therascreen assay was equivalent to that in patients identified as KRAS wild-type
      using the LNA assay. This was determined by assessing if the concordance between
      the therascreen assay and the LNA assay met the minimum threshold (prespecified
      as 0.8) to achieve a significant difference in the OS hazard ratio in favor of
      the cetuximab + FOLFIRI (5-fluorouracil, leucovorin [folinic acid], irinotecan)
      arm in the KRAS wild-type population as identified using the therascreen assay.
      RESULTS: Of the 148 samples determined to be KRAS wild-type (therascreen assay),
      141 (95.3%) samples were also KRAS wild-type (LNA assay) and 7 samples (4.7%)
      were KRAS mutant (LNA assay). The prespecified primary concordance measure p was
      141/148 = 0.953 (95% confidence interval [CI], 0.905-0.981). The concordance was
      statistically significantly higher than the prespecified threshold of 0.8 for
      concordance between the therascreen assay and the LNA assay. Consistent with the
      concordance exceeding the prespecified threshold, the OS hazard ratio (cetuximab
      + FOLFIRI arm vs. FOLFIRI arm) in the KRAS wild-type population, determined by
      the therascreen assay, supported a significant benefit for cetuximab (ie, the 95%
      CI excluded 1) and was comparable to the OS hazard ratio observed in the CRYSTAL
      study KRAS wild-type population (LNA assay) even after adjustment for potentially
      confounding baseline variables. CONCLUSION: These results support the utility of
      the therascreen assay for identifying patients who may benefit from cetuximab
      therapy for metastatic colorectal cancer.

PMID- 23978463
TI  - Physical activity in community-dwelling stroke survivors and a healthy population
      is not explained by motor function only.
AB  - OBJECTIVES: To explore the relationship between self-reporting and physical
      measures and compare self-reported physical activity (PA) levels in persons who
      have had a stroke with self-reported PA levels in a control population. DESIGN:
      Cross-sectional assessment of a convenience sample of survivors of a stroke
      living in the community and a population-based sample from the same community.
      SETTING: University hospital. PARTICIPANTS: Seventy persons (48 men and 22 women;
      average age, 60 years) who had a stroke a mean of 6 years earlier and 141 persons
      (70 men and 71 women; average age, 59 years) who served as control subjects. MAIN
      OUTCOME MEASUREMENTS: The Physical Activity Scale for the Elderly (PASE) was
      used, and self-selected and maximum walking speeds were measured. Motor function
      after stroke was assessed with the Fugl-Meyer Assessment. RESULTS: The median
      Fugl-Meyer score for motor function in the leg was 29. Mean self-selected and
      maximum walking speeds after having a stroke were 1.0 m/s and 1.3 m/s,
      corresponding to 72% and 65% of control values. A regression model with PASE as
      the dependent variable and age and walking speed as independent variables
      explained 29% (P < .001) of the variation in the stroke group. For the control
      group, age and self-selected walking speed explained 8% of the variation (P <
      .01). The mean PASE score in the stroke group was 119, compared with 161 in the
      control group. CONCLUSION: Persons who have experienced a stroke and live in the
      community are less physically active than the population of the same age who have
      not had a stroke. However, it appears that factors other than motor impairment
      have an impact on a person's PA level, because only a low association was found
      between PA level and motor function, with a large dispersion in PA levels in
      persons with a history of stroke who were physically well recovered.

PMID- 23978464
TI  - Urinary incontinence in adults with cerebral palsy: prevalence, type, and effects
      on participation.
AB  - OBJECTIVE: To assess the prevalence, type, and impact of urinary problems in
      adults with cerebral palsy and their relation with the Gross Motor Function
      Classification System for cerebral palsy. DESIGN: A cross-sectional prospective
      survey study. SETTING: An outpatient, urban, academic rehabilitation clinic.
      PARTICIPANTS: Ninety-one adults with cerebral palsy (45 women, 46 men).
      INTERVENTIONS: Subjects were approached at clinic presentation and were
      interviewed regarding current function, type and incidence of bladder issues, and
      concerns with bladder problems. MAIN OUTCOME MEASURES: The International
      Consultation on Incontinence Questionnaire-Female, or the International
      Consultation on Incontinence Questionnaire-Male Lower Urinary Tract Symptoms
      Module, Gross Motor Function Classification System, employment, and type of
      residence. RESULTS: The mean age for both women and men was 36 years (range, 18
      79 years). The subjects were currently assessed with the Gross Motor Function
      Classification System scales I-V: I, 4.4%; II, 19.8%; III, 13.2%; IV, 40.7%; and
      V, 22.0%. 95.6% of females and 84.7% of males were living at home. Twenty-three
      percent were currently employed. Twenty percent of the women indicated that they
      had bladder urgency most to all of the time and 46.7% of the women had leakage
      that occurred 2-3 times per week to several times per day. In men, urgency that
      occurred more often than "occasionally" was reported by 45.7%, and 19.6% reported
      this occurred "most to all of the time." Multivariable analyses found that
      obesity compared with normal weight was significantly related to leaking before
      reaching a toilet (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.3-14.7),
      to leaking with cough, exercise, or sneeze (OR 5.6, 95% CI 1.3-23.1), and to
      nocturia (OR 5.4, 95% CI 1.2-25.1). Women were more likely to leak with cough,
      exercise, or sneeze (OR 5.5, 95% CI 1.5-20.0). On scales that indicate symptom
      interference with life, high levels of interference were reported for women with
      symptoms of leaking and for men with urgency and leaking. No significant
      differences in living situation or employment were related to incontinence scores
      for women or men. CONCLUSION: There are high levels of incontinence in adults
      with cerebral palsy, and these individuals report interference with quality of
      life. Despite these issues, most participants were living in the community, and
      incontinence scores were not related to employment.

PMID- 23978465
TI  - The source of fluid deep to the iliotibial band: documentation of a potential
      intra-articular source.
AB  - OBJECTIVE: To determine whether there is a consistent extension of the lateral
      synovial recess under the iliotibial band (ITB) in an unembalmed cadaveric model.
      DESIGN: A prospective laboratory investigation. SETTING: A procedural skills
      laboratory of a tertiary medical center. SUBJECTS: Twelve unembalmed cadaveric
      knee specimens. METHODS: The suprapatellar recess, ITB, and region deep to the
      ITB were examined sonographically to document the absence of fluid in each knee.
      Thereafter, 60 mL of normal saline solution was injected into each knee to
      distend the joint recesses. Postinjection sonographic examination of the ITB at
      the level of the lateral femoral epicondyle was repeated at 0 degrees , 25
      degrees , and 45 degrees  of knee flexion to detect and characterize any fluid
      visualized in the region of the ITB. The location of fluid in relation to the ITB
      was recorded as anterior, deep, posterior, or a combination of these positions.
      RESULTS: Fluid was observed anterior and deep to the ITB in 100% of 12 specimens.
      In 2 specimens, fluid also was noted posterior to the ITB. The presence and
      location of the fluid did not appear to change as a function of knee position.
      Using dynamic sonographic evaluation, we could track the fluid deep to the ITB
      back to the knee joint. CONCLUSIONS: The lateral synovial recess appears to
      regularly extend beneath the anterior ITB. Fluid deep to the ITB should
      precipitate further evaluation of the knee joint when clinically indicated.
      Although distention of the lateral synovial recess is not always symptomatic,
      synovial irritation may be a pathoetiologic factor in the production of lateral
      knee pain syndromes, including ITB syndrome.

PMID- 23978466
TI  - The decision to provide testosterone supplementation in patients with traumatic
      brain injury.

PMID- 23978467
TI  - Antidepressants suppress neuropathic pain by a peripheral beta2-adrenoceptor
      mediated anti-TNFalpha mechanism.
AB  - Neuropathic pain is pain arising as a direct consequence of a lesion or disease
      affecting the somatosensory system. It is usually chronic and challenging to
      treat. Some antidepressants are first-line pharmacological treatments for
      neuropathic pain. The noradrenaline that is recruited by the action of the
      antidepressants on reuptake transporters has been proposed to act through beta2
      adrenoceptors (beta2-ARs) to lead to the observed therapeutic effect. However,
      the complex downstream mechanism mediating this action remained to be identified.
      In this study, we demonstrate in a mouse model of neuropathic pain that an
      antidepressant's effect on neuropathic allodynia involves the peripheral nervous
      system and the inhibition of cytokine tumor necrosis factor alpha (TNFalpha)
      production. The antiallodynic action of nortriptyline is indeed lost after
      peripheral sympathectomy, but not after lesion of central descending
      noradrenergic pathways. More particularly, we report that antidepressant
      recruited noradrenaline acts, within dorsal root ganglia, on beta2-ARs expressed
      by non-neuronal satellite cells. This stimulation of beta2-ARs decreases the
      neuropathy-induced production of membrane-bound TNFalpha, resulting in relief of
      neuropathic allodynia. This indirect anti-TNFalpha action was observed with the
      tricyclic antidepressant nortriptyline, the selective serotonin and noradrenaline
      reuptake inhibitor venlafaxine and the beta2-AR agonist terbutaline. Our data
      revealed an original therapeutic mechanism that may open novel research avenues
      for the management of painful peripheral neuropathies.

PMID- 23978468
TI  - Anti-epileptogenesis: Electrophysiology, diffusion tensor imaging and behavior in
      a genetic absence model.
AB  - The beneficial effects of chronic and early pharmacological treatment with
      ethosuximide on epileptogenesis were studied in a genetic absence epilepsy model
      comorbid for depression. It was also investigated whether there is a critical
      treatment period and treatment length. Cortical excitability in the form of
      electrical evoked potentials, but also to cortico-thalamo-cortical network
      activity (spike-wave discharges, SWD and afterdischarges), white matter changes
      representing extra cortico-thalamic functions and depressive-like behavior were
      investigated. WAG/Rij rats received either ethosuximide for 2 months (post natal
      months 2-3 or 4-5), or ethosuximide for 4 months (2-5) in their drinking water,
      while control rats drank plain water. EEG measurements were made during
      treatment, and 6 days and 2 months post treatment. Behavioral test were also done
      6 days post treatment. DTI was performed ex vivo post treatment. SWD were
      suppressed during treatment, and 6 days and 2 months post treatment in the 4
      month treated group, as well as the duration of AD elicited by cortical
      electrical stimulation 6 days post treatment. Increased fractional anisotropy in
      corpus callosum and internal capsula on DTI was found, an increased P8 evoked
      potential amplitude and a decreased immobility in the forced swim test. Shorter
      treatments with ETX had no large effects on any parameter. Chronic ETX has
      widespread effects not only within but also outside the circuitry in which SWD
      are initiated and generated, including preventing epileptogenesis and reducing
      depressive-like symptoms. The treatment of patients before symptom onset might
      prevent many of the adverse consequences of chronic epilepsy.

PMID- 23978470
TI  - Distinct mechanisms control contrast adaptation over different timescales.
AB  - Changes to the visual environment can happen at many timescales, from very
      transient to semi-permanent. To adapt optimally, the visual system also adjusts
      at different timescales, with longer-lasting environmental changes producing
      longer-lasting effects, but how the visual system adapts in this way remains
      unknown. Here, we show that contrast adaptation-the most-studied form of visual
      adaptation-has multiple controllers, each operating over a different time scale.
      In a series of experiments, subjects completed either a contrast matching,
      contrast detection, or tilt adjustment task, while adapting to contrast at one
      orientation. Following a relatively longer period (5 min) of adaptation to high
      contrast, subjects were "deadapted" for a shorter period (e.g., 40 s) to a lower
      contrast. Deadaptation eliminated perceptual aftereffects of adaptation, but
      continued testing in a neutral environment revealed their striking recovery.
      These results suggest the following account: Adaptation was controlled by at
      least two mechanisms, with initial adaptation affecting a longer-term one and
      deadaptation affecting a shorter-term one in the opposite direction. Immediately
      following deadaptation, the effects of the two mechanisms cancelled each other,
      but the short-term effects rapidly decayed, revealing ongoing longer-term
      adaptation. A single controlling mechanism cannot account for the observed
      recovery of effects, since once deadaptation cancels the initial longer-term
      adaptation, no trace of it remains. Combined with previous results at very long
      adaptation durations, the present results suggest that contrast adaptation is
      possibly controlled by a continuum of mechanisms acting over a large range of
      timescales. 

PMID- 23978469
TI  - Promoter methylation represses AT2R gene and increases brain hypoxic-ischemic
      injury in neonatal rats.
AB  - Perinatal nicotine exposure downregulated angiotensin II type 2 receptor (AT2R)
      in the developing brain and increased brain vulnerability to hypoxic-ischemic
      injury in male neonatal rats. We tested the hypothesis that site-specific CpG
      methylation at AT2R gene promoter contributes to the increased vulnerability of
      brain injury in the neonate. Nicotine was administered to pregnant rats from day
      4 of gestation to day 10 after birth. Brain hypoxic-ischemic injury was induced
      in day 10 male pups. CpG methylation at AT2R promoter was determined in the brain
      by quantitative methylation-specific PCR. Nicotine exposure significantly
      increased the methylation of a single CpG-52 locus near the TATA-box at AT2R
      promoter. Electrophoretic mobility shift assay indicated that the methylation of
      CpG-52 significantly decreased the binding affinity of TATA-binding protein
      (TBP). Chromatin immunoprecipitation assay further demonstrated an increase in
      the binding of a methyl-binding protein and a decrease in TBP binding to AT2R
      promoter in vivo in neonatal brains of nicotine-treated animals. This resulted in
      AT2R gene repression in the brain. Intracerebroventricular administration of a
      demethylating agent 5-aza-2'-deoxycytidine abrogated the enhanced methylation of
      CpG-52, rescued the TBP binding, and restored AT2R gene expression. Of
      importance, 5-aza-2'-deoxycytidine reversed the nicotine-increased vulnerability
      of brain hypoxic-ischemic injury in the neonate. The finding provides mechanistic
      evidence of increased promoter methylation and resultant AT2R gene repression in
      the developing brain linking perinatal stress and a pathophysiological
      consequence of heightened vulnerability of brain hypoxic-ischemic encephalopathy
      in the neonate.

PMID- 23978471
TI  - Isolated left brachiocephalic trunk arising from the main pulmonary artery with
      right aortic arch.

PMID- 23978472
TI  - Impact of ABO compatibility on outcomes after heart transplantation in a national
      cohort during the past decade.
AB  - BACKGROUND: Immunologic incompatibility has implications for primary graft
      failure, rejection, and survival in heart transplantation. To our knowledge, this
      is the first large cohort study investigating the impact of ABO-compatible versus
      identical blood type matching on post heart transplantation survival. METHODS: We
      used a nationwide sample (2000-2010) within the United Network for Organ Sharing
      database. Stratification was between ABO-identical and ABO-compatible heart
      transplantations for univariate and multivariate analyses. The primary end point
      was graft failure from all causes. Posttransplant survival was compared between
      groups using Cox proportional hazard and logistic regression models. RESULTS: A
      total of 17,951 patients met inclusion criteria, and 2684 (approximately 15%)
      underwent ABO-compatible heart transplantation. ABO-compatible recipients were
      generally sicker than ABO-identical recipients before transplant because more
      were status 1A, in the intensive care unit, and receiving mechanical ventilatory
      support (P < .05). Univariate analysis correlated ABO-compatible transplants with
      decreased posttransplant survival and a higher incidence of primary graft failure
      as cause of death (P < .05). There was no significant difference in acute graft
      rejection (P = .53). Multivariate analysis, however, did not demonstrate adverse
      outcomes in terms of decreased graft survival (hazard ratio, 0.99; P = .87).
      Blood type O donor grafts were associated with poorer outcomes compared with all
      other types (P < .05). CONCLUSIONS: ABO-compatible transplantation does not
      result in adverse outcomes with respect to graft survival. Blood type O donor
      grafts, however, were associated with decreased survival. This has important
      implications for current graft allocation policies, particularly for type B
      recipients.

PMID- 23978474
TI  - Endothelial cells provide a niche for placental hematopoietic stem/progenitor
      cell expansion through broad transcriptomic modification.
AB  - Umbilical cord blood (UCB) is an attractive source of hematopoietic stem cells
      (HSCs). However, the number of HSCs in UCB is limited, and attempts to amplify
      them in vitro remain inefficient. Several publications have documented
      amplification of hematopoietic stem/progenitor cells (HSPCs) on endothelial or
      mesenchymal cells, but the lack of homogeneity in culture conditions and HSC
      definition impairs direct comparison of these results. We investigated the
      ability of different feeder layers, mesenchymal progenitors (MPs) and endothelial
      cells (ECs), to amplify hematopoietic stem/progenitor cells. Placental derived
      HSPCs (defined as Lin(-)CD45(-/dim)CD34(+)CD38(-)CD90(+)) were maintained on
      confluent feeder layers and the number of cells and their marker expression were
      monitored over 21 days. Although both types of feeder layers supported
      hematopoietic expansion, only endothelial cells triggered amplification of Lin(
      )CD45(-/dim)CD34(+)CD38(-)CD90(+) cells, which peaked at 14 days. The amplified
      cells differentiated into all cell lineages, as attested by in vitro colony
      forming assays, and were capable of engraftment and multi-lineage differentiation
      in sub-lethally irradiated mice. Mesenchymal progenitors promoted amplification
      of CD38(+) cells, previously defined as precursors with more limited
      differentiation potential. A competitive assay demonstrated that hematopoietic
      stem/progenitor cells had a preference for interacting with endothelial cells in
      vitro. Cytokine and transcriptomic analysis of both feeder cell types identified
      differences in gene expression that correlated with propensity of ECs and MPs to
      support hematopoietic cell amplification and differentiation respectively.
      Finally, we used RNA sequencing of endothelial cells and HSPCs to uncover
      relevant networks illustrating the complex interaction between endothelial cells
      and HSPCs leading to stem/progenitor cell expansion.

PMID- 23978475
TI  - PRDM11 is dispensable for the maintenance and function of hematopoietic stem and
      progenitor cells.
AB  - Hematopoietic stem cells (HSC)(1) supply organisms with life-long output of
      mature blood cells. To do so, the HSC pool size has to be maintained by HSC self
      renewing divisions. PRDM3 and PRDM16 have been documented to regulate HSC self
      renewal, maintenance and function. We found Prdm11 to have similar expression
      patterns in the hematopoietic stem and progenitor cell (HSPC) compartments as
      Prdm3 and Prdm16. Therefore, we undertook experiments to test if PRDM11 regulates
      HSC self-renewal, maintenance and function by investigating the Prdm11(-/-) mice.
      Our data shows that phenotypic HSPCs are intact in bone marrow (BM) of one-year
      old Prdm11(-/-) mice. In addition, Prdm11(-/-) mice were able to fully regenerate
      the hematopoietic system upon BM transplantation (BMT) into lethally irradiated
      mice with a mild drop in lymphoid output only. Taken together, this suggests that
      PRDM11, in contrast to PRDM3 and PRDM16, is not directly involved in regulation
      of HSPCs in mice. 

PMID- 23978476
TI  - Cardiometabolic changes in treated versus never treated HIV-infected black South
      Africans: the PURE study.
AB  - BACKGROUND: The use of antiretroviral treatment is known to be accompanied by
      several negative health outcomes and may negatively affect a country such as
      South Africa, which is the most burdened by the human immunodeficiency virus
      (HIV) in the world. We aimed to determine whether receiving antiretroviral
      treatment changes the cardiometabolic profile of HIV-infected South Africans.
      METHODS: In this sub-study, embedded in the Prospective Urban and Rural
      Epidemiology (PURE) study, we compared the cardiometabolic profile in a cohort of
      66 treated and 71 never treated HIV-infected participants from the North-West
      province, South Africa. By using standard techniques, these participants'
      cardiometabolic, biochemical and lifestyle variables were assessed in 2005 and
      2010, respectively. RESULTS: The treated group showed a higher percentage change
      in pulse pressure (13.3%; p = 0.004), systolic blood pressure (4.5%; p = 0.029)
      and CD4 cell count (9.2%; p = 0.009) levels over five years. During follow-up
      (2010), lipid variables were worse in the treated group. Further, antiretroviral
      treatment was associated with the percentage change in pulse pressure (R(2) =
      0.24; beta = 0.19; p = 0.020). CONCLUSIONS: We concluded that Africans receiving
      antiretroviral treatment had a greater increase in pulse pressure and systolic
      blood pressure, as well as an unfavourable lipid profile when compared to never
      treated participants. Whether, in the long term, antiretroviral treatment will
      lead to increased arterial stiffness and/or accelerated atherosclerosis among
      this HIV-infected African population remains to be seen.

PMID- 23978477
TI  - Non-classical effects of estradiol on cAMP responsive element binding protein
      phosphorylation in gonadotropin-releasing hormone neurons: mechanisms and role.
AB  - Gonadotropin-releasing hormone (GnRH) is produced by a heterogenous neuronal
      population in the hypothalamus to control pituitary gonadotropin production and
      reproductive function in all mammalian species. Estradiol is a critical component
      for the communication between the gonads and the central nervous system.
      Resolving the mechanisms by which estradiol modulates GnRH neurons is critical
      for the understanding of how fertility is regulated. Extensive studies during the
      past decades have provided compelling evidence that estradiol has the potential
      to alter the intracellular signal transduction mechanisms. The common target of
      many signaling pathways is the phosphorylation of a key transcription factor, the
      cAMP response element binding protein (CREB). This review first addresses the
      aspects of estradiol action on CREB phosphorylation (pCREB) in GnRH neurons.
      Secondly, this review considers the receptors and signaling network that
      regulates estradiol's action on pCREB within GnRH neurons and finally it
      summarizes the physiological significance of CREB to estrogen feedback. 

PMID- 23978478
TI  - Ecophysiological characteristics and biogas production of cadmium-contaminated
      crops.
AB  - The present study proposes a novel strategy to get a rational production of
      biogas of the biomass residues from phytoremediation. This study investigates
      physiological responses, cadmium (Cd) accumulation and biogas production from
      canola, oat and wheat in pot and batch experiments. The results indicate that (1)
      aerial biomasses for canola, oat and wheat were enhanced by 5 mg Cd/kg soil by
      19.41%, 8.78% and 3.38%, and the upper limit of Cd concentration that canola, oat
      and wheat can tolerate for aerial biomass production were 50, 10 and 10 mg Cd/kg
      soil; (2) canola accumulates more Cd than oat and wheat in its aerial parts; (3)
      cumulative biogas yields were 159.37%, 179.23% and 111.34% of the control when Cd
      in the shoot were 2.00+/-0.44, 39.80+/-1.25 and 6.37+/-0.15 mg Cd/kg biomass for
      canola, oat and wheat. Phytoremediation in cooperation with bioenergy production
      provide new insights for both soil remediation and energy research.

PMID- 23978479
TI  - Enhancement stabilization of heavy metals (Zn, Pb, Cr and Cu) during
      vermifiltration of liquid-state sludge.
AB  - This paper illustrated the potential effect of earthworms on heavy metal
      stabilization after vermifiltration of liquid-state sludge. Significant
      enhancement of organics degradation in sludge caused an increase of heavy metal
      concentrations in VF effluent sludge. However, the analysis of heavy metal
      chemical speciation indicated earthworms made unstable fractions of heavy metals
      transformed into stable fractions. Further investigation using principal
      component analysis revealed that transformations of heavy metal fractions were
      mainly due to the changes in sludge physico-chemical properties of pH, soluble
      chemical oxygen demand and available phosphorus. The bioassay of earthworms
      indicated that only zinc was accumulated by earthworms because the unstable
      fraction was its main chemical speciation. Furthermore, risk analysis
      demonstrated that earthworm activities weakened heavy metal risk due to the
      formation of stable fractions although their total concentrations increased.
      These results indicated that earthworms in vermifilter had a positive role in
      stabilizing heavy metals in sewage sludge. 

PMID- 23978480
TI  - A novel production process for optically pure L-lactic acid from kitchen refuse
      using a bacterial consortium at high temperatures.
AB  - We investigated L-lactic acid production in static batch fermentation of kitchen
      refuse using a bacterial consortium from marine-animal-resource (MAR) composts at
      temperatures ranging from 30 to 65  degrees C. At relatively low temperatures
      butyric acid accumulated, whereas at higher temperatures L-lactic acid was
      produced. In particular, fermentation at 50  degrees C produced 34.5 g L(-1) L
      lactic acid with 90% lactic acid selectivity and 100% optical purity. Denaturing
      gradient gel electrophoresis indicated that dominant bacteria present in the
      original MAR composts diminished rapidly and Bacillus coagulans strains became
      the dominant contributors to L-lactic acid production at 45, 50 and 55  degrees
      C. This is the first report of the achievement of 100% optical purity of L-lactic
      acid using a bacterial consortium.

PMID- 23978481
TI  - T cell recognition of beryllium.
AB  - Chronic beryllium disease (CBD) is a granulomatous lung disorder caused by a
      hypersensitivity to beryllium and characterized by the accumulation of beryllium
      specific CD4(+) T cells in the lung. Genetic susceptibility to beryllium-induced
      disease is strongly associated with HLA-DP alleles possessing a glutamic acid at
      the 69th position of the beta-chain (betaGlu69). The structure of HLA-DP2, the
      most prevalent betaGlu69-containing molecule, revealed a unique solvent-exposed
      acidic pocket that includes betaGlu69 and represents the putative beryllium
      binding site. The delineation of mimotopes and endogenous self-peptides that
      complete the alphabetaTCR ligand for beryllium-specific CD4(+) T cells suggests a
      unique role of these peptides in metal ion coordination and the generation of
      altered self-peptides, blurring the distinction between hypersensitivity and
      autoimmunity. 

PMID- 23978482
TI  - Associations between single nucleotide polymorphisms in thyroid hormone
      transporter genes (MCT8, MCT10 and OATP1C1) and circulating thyroid hormones.
AB  - BACKGROUND: Thyroid hormone (TH) action takes place intracellularly; therefore,
      transport across the plasma membrane by specific TH transporters, such as MCT8,
      MCT10 and OATP1C1, is necessary. Several single nucleotide polymorphisms (SNPs)
      in these genes were reported to be associated with TH concentrations; however,
      results have been inconsistent. METHODS: Six SNPs in TH transporter genes
      (rs5937843-G/T and rs6647476-T/C in MCT8, rs14399-C/A in MCT10, rs10444412-C/T,
      rs10770704-C/T and rs36010656-C/A in OATP1C1) were genotyped in 2 cohorts; one
      consisting of 2416 men and women aged 35-55 yrs (Asklepios), and the other of 941
      men aged 25-45 yrs (Siblos), using KASPar technology. TSH, FT3, FT4 and total T3
      were determined by immuno-electrochemiluminescence in both cohorts; in the second
      cohort additional determination of total T4 by electrochemiluminescence and of
      reverse T3 (rT3) and thyroid binding globulin (TBG) by radioimmunoassays was
      performed. RESULTS: The first SNP in MCT8 (rs5937843-G/T) was inversely
      associated with FT4 concentrations in men but not in women. In Siblos, this SNP
      showed also negative associations with TT4 and rT3; in men from Asklepios a trend
      for positive association with TSH was observed. The second SNP in MCT8 (rs6647476
      T/C) was negatively associated with FT3 levels in men from the Siblos and the
      Asklepios cohort. In addition, an inverse association with TT3 levels in men from
      the Siblos was observed. Rs36010656 (C/A) in OATP1C1 was not in Hardy-Weinberg
      equilibrium and therefore excluded from further analyses. The other 2 SNPs in
      OATP1C1 (rs10444412-C/T and rs10770704-C/T) and the SNP in MCT10 (rs14399-C/A)
      were not related to TH levels in either cohort. CONCLUSION: Two SNPs in MCT8 were
      related to circulating thyroid hormone levels in men but not in women: the
      rs5937843 polymorphism (G/T) was inversely associated with FT4 levels and the
      rs6647476 (T/C) polymorphism related negatively to circulating FT3.

PMID- 23978483
TI  - Head-to-head comparison of high-sensitivity troponin T and sensitive-contemporary
      troponin I regarding heart failure risk stratification.
AB  - BACKGROUND: High-sensitivity assays for cardiac troponins have recently become
      available, increasing the value of troponins in heart failure (HF)
      prognostication. We head-to-head compared the prognostic significance of high
      sensitivity cardiac troponin T (hs-cTnT) and sensitive-contemporary cardiac
      troponin I (sc-cTnI) in an outpatient HF population. METHODS: We studied 876
      patients, mainly of ischemic etiology (52.1%). Median left ventricular ejection
      fraction was 34%. Median follow-up was 3.45 years. Comprehensive statistical
      measurements of performance (discrimination, calibration, and reclassification)
      were obtained. RESULTS: hs-cTnT was ubiquitous in the patient cohort; sc-cTnI was
      detected in 276 patients (31.5%). During follow-up 311 patients died. According
      to multivariable Cox regression analysis, both hs-cTnT (HR 2.09, 95% CI 1.46
      2.99, P<0.001) and sc-cTnI (HR 1.61, 95% CI 1.24-2.08, P<0.001) remained
      independent predictors of all cause and cardiovascular mortality. Using the best
      predictive cut-off point for both troponins calibration was better for hs-cTnT,
      which also reclassified a larger number of patients (NRI 9.0 [2.5;15.5] P =
      0.007). The higher sensitivity of hs-cTnT permitted the identification of almost
      the double of deaths. CONCLUSION: Both hs-cTnT and sc-cTnI predict mortality in a
      real-life cohort of ambulatory HF patients. However, hs-cTnT showed globally
      better measures of performance and identified a higher proportion of decedents
      during follow-up.

PMID- 23978485
TI  - Sorption of uranium from aqueous solutions using palm-shell-based adsorbents: a
      kinetic and equilibrium study.
AB  - In this study adsorbents based on palm shell powder as well as modified and
      activated palm shell powder were studied to analyze their behavior in sorbing
      U(6+) by both batch and fixed column modes. Seven different two-parameter
      isotherm models were applied to the experimental data to predict the sorption
      isotherms. The DeltaG(0) values from Langmuir and thermodynamic calculations
      indicate physisorption as the major mechanism for adsorption of uranium.
      Usefulness of various kinetic models like pseudo first order, pseudo second
      order, intraparticle diffusion, Bangham, Elovich and Liquid film diffusion were
      tested. The adsorption capacities were found to be greater than 200 mg/g for all
      the adsorbents under study. The column data were fitted by Thomas, Yoon and
      Nelson as well as Wolborska models. The Thomas and Yoon and Nelson models were
      best to fit the breakthrough curves under the experimental conditions studied.

PMID- 23978484
TI  - An assessment of 25-hydroxyvitamin D measurements in comparability studies
      conducted by the Vitamin D Metabolites Quality Assurance Program.
AB  - BACKGROUND: The National Institute of Standards and Technology (NIST), in
      collaboration with the National Institutes of Health Office of Dietary
      Supplements, established the first accuracy-based program for improving the
      comparability of vitamin D metabolite measurements, the Vitamin D Metabolites
      Quality Assurance Program. METHODS: The study samples were human serum or plasma
      Standard Reference Materials (SRMs) with 25-hydroxyvitamin D values that were
      determined at NIST. Participants evaluated the materials using immunoassay (IA),
      liquid chromatography (LC) with mass spectrometric detection, and LC with
      ultraviolet absorbance detection. NIST evaluated the results for concordance
      within the participant community as well as trueness relative to the NIST value.
      RESULTS: For the study materials that contain mostly 25-hydroxyvitamin D3
      (25(OH)D3),the coefficient of variation (CV) for the participant results was
      consistently in the range from 7% to 19%, and the median values were biased high
      relative to the NIST values. However, for materials that contain significant
      concentrations of both 25-hydroxyvitamin D2 (25(OH)D2) and 25(OH)D3, the median
      IA results were biased lower than both the LC and the NIST values, and the CV was
      as high as 28%. The first interlaboratory comparison results for SRM 972a Vitamin
      D Metabolites in Human Serum are also reported. CONCLUSIONS: Relatively large
      within-lab and between-lab variability hinders conclusive assessments of bias and
      accuracy.

PMID- 23978486
TI  - Allopregnanolone and mood disorders.
AB  - Certain women experience negative mood symptoms during the menstrual cycle and
      progesterone addition in estrogen treatments. In women with PMDD increased
      negative mood symptoms related to allopregnanolone increase during the luteal
      phase of ovulatory menstrual cycles. In anovulatory cycles no symptom or sex
      steroid increase occurs. This is unexpected as positive modulators of the GABA-A
      receptor are generally increasing mood. This paradoxical effect has brought
      forward a hypothesis that the symptoms are provoked by allopregnanolone the GABA
      A receptor system. GABA-A is the major inhibitory system in the brain. Positive
      modulators of the GABA-A receptor include the progesterone metabolites
      allopregnanolone and pregnanolone, benzodiazepines, barbiturates, and alcohol.
      GABA-A receptor modulators are known, in low concentrations to induce adverse,
      anxiogenic effects whereas in higher concentrations show beneficial, calming
      properties. Positive GABA-A receptor modulators induce strong paradoxical effects
      e.g. negative mood in 3-8% of those exposed, while up to 25% have moderate
      symptoms thus similar as the prevalence of PMDD, 3-8% among women in fertile
      ages, and up to 25% have moderate symptoms of premenstrual syndrome (PMS). The
      mechanism behind paradoxical reaction might be similar among them who react on
      positive GABA-A receptor modulators and in women with PMDD. In women the severity
      of these mood symptoms are related to the allopregnanolone serum concentrations
      in an inverted U-shaped curve. Negative mood symptoms occur when the serum
      concentration of allopregnanolone is similar to endogenous luteal phase levels,
      while low and high concentrations have less effect on mood. Low to moderate
      progesterone/allopregnanolone concentrations in women increases the activity in
      the amygdala (measured with fMRI) similar to the changes seen during anxiety
      reactions. Higher concentrations give decreased amygdala activity similar as seen
      during benzodiazepine treatment with calming anxiolytic effects. Patients with
      PMDD show decreased sensitivity in GABA-A receptor sensitivity to diazepam and
      pregnanolone while increased sensitivity to allopregnanolone. This agrees with
      findings in animals showing a relation between changes in alpha4 and delta
      subunits of the GABA-A receptor and anxiogenic effects of allopregnanolone.
      CONCLUSION: These findings suggest that negative mood symptoms in women with PMDD
      are caused by the paradoxical effect of allopregnanolone mediated via the GABA-A
      receptor.

PMID- 23978487
TI  - Development and use of active clinical decision support for preemptive
      pharmacogenomics.
AB  - BACKGROUND: Active clinical decision support (CDS) delivered through an
      electronic health record (EHR) facilitates gene-based drug prescribing and other
      applications of genomics to patient care. OBJECTIVE: We describe the development,
      implementation, and evaluation of active CDS for multiple pharmacogenetic test
      results reported preemptively. MATERIALS AND METHODS: Clinical pharmacogenetic
      test results accompanied by clinical interpretations are placed into the
      patient's EHR, typically before a relevant drug is prescribed. Problem list
      entries created for high-risk phenotypes provide an unambiguous trigger for
      delivery of post-test alerts to clinicians when high-risk drugs are prescribed.
      In addition, pre-test alerts are issued if a very-high risk medication is
      prescribed (eg, a thiopurine), prior to the appropriate pharmacogenetic test
      result being entered into the EHR. Our CDS can be readily modified to incorporate
      new genes or high-risk drugs as they emerge. RESULTS: Through November 2012, 35
      customized pharmacogenetic rules have been implemented, including rules for TPMT
      with azathioprine, thioguanine, and mercaptopurine, and for CYP2D6 with codeine,
      tramadol, amitriptyline, fluoxetine, and paroxetine. Between May 2011 and
      November 2012, the pre-test alerts were electronically issued 1106 times (76 for
      thiopurines and 1030 for drugs metabolized by CYP2D6), and the post-test alerts
      were issued 1552 times (1521 for TPMT and 31 for CYP2D6). Analysis of alert
      outcomes revealed that the interruptive CDS appropriately guided prescribing in
      95% of patients for whom they were issued. CONCLUSIONS: Our experience
      illustrates the feasibility of developing computational systems that provide
      clinicians with actionable alerts for gene-based drug prescribing at the point of
      care.

PMID- 23978488
TI  - Marked elevation of interleukin-6 in mild encephalopathy with a reversible
      splenial lesion (MERS) associated with acute focal bacterial nephritis caused by
      Enterococcus faecalis.
AB  - This report describes two cases of mild encephalitis/encephalopathy with
      reversible splenial lesion (MERS) associated with acute focal bacterial nephritis
      (AFBN). The patients, who presented with fever and delirious behavior, exhibited
      hyponatremia and markedly elevated interleukin (IL)-6 in cerebrospinal fluid
      (CSF) and serum. Enterococcus faecalis was detected in the urine culture. After
      ampicillin treatment, their consciousness improved without neurological sequelae.
      Moreover, a diffusion-weighted MRI abnormality, i.e., intensified signals in
      splenium of the corpus callosum, disappeared. MERS is a possible complication of
      AFBN. Elevated CSF IL-6 levels suggest that remote activation of intracerebral
      immune response through the immune-neuroendocrine pathway might play an important
      role in the pathophysiology of MERS. 

PMID- 23978489
TI  - Differences between periventricular hemorrhagic infarction and periventricular
      leukomalacia.
AB  - PURPOSE: To clarify the differences between infants with periventricular
      hemorrhagic infarction (PVHI) and those with periventricular leukomalacia (PVL).
      METHODS: We retrospectively evaluated the clinical features, ultrasonography, and
      electroencephalogram (EEG) findings in 22 preterm infants with PVHI and 49 with
      PVL. EEG and cranial ultrasonography were serially performed in all participants
      starting immediately after birth. Acute and chronic stage EEG abnormalities were
      evaluated separately. RESULTS: Gestational age and birth weight were
      significantly lower in infants with PVHI than those with PVL. EEGs were normal in
      the majority of infants with PVHI on days 1-2. However, EEG abnormalities
      appeared after ultrasonography abnormalities. The majority of infants with PVL
      showed acute-stage EEG abnormalities on days 1-2. The rate of infants with acute
      stage EEG abnormalities decreased with age, whereas the rate of infants with
      chronic-stage EEG abnormalities increased with age. Normal EEG before
      ultrasonography abnormalities was more common in infants with PVHI than in those
      with PVL. However, deterioration of acute-stage EEG abnormalities was more
      frequent in infants with PVHI than in those with PVL. CONCLUSIONS: PVHI was
      presumed to cause mostly postnatal injury, whereas PVL was presumed to cause
      mostly pre-or perinatal injury.

PMID- 23978490
TI  - Clinical manifestations of Clostridium difficile infection in a medical center in
      Taiwan.
AB  - BACKGROUND/PURPOSE: To investigate the clinical characteristics of Clostridium
      difficile infection (CDI) at a medical center in Taiwan. METHODS: Patients with
      CDI were identified from medical records at the National Taiwan University
      Hospital (Taipei, Taiwan). The following information was gathered and analyzed to
      better understand the clinical manifestations of CDI: age; sex; underlying
      immunocompromised conditions; laboratory data; in-hospital mortality; and
      previous use of drugs such as antimicrobial agents, steroids, and antipeptic
      ulcer agents. RESULTS: During the years 2000-2010, 122 patients were identified
      as having CDI. This included 92 patients with nontoxigenic CDI (i.e., positive
      stool culture for C. difficile but negative results for toxins A and B) and 30
      patients with toxigenic CDI (i.e., positive stool culture cultures for C.
      difficile and positive results for toxins A and B). Of the 122 patients, 48 (39%)
      patients were older than 65 years and most patients acquired the CDI while in the
      hospital. Active cancer was the most common reason for hospitalization, followed
      by diabetes mellitus, and end-stage renal disease. More than 90% of the patients
      had received antibiotics before acquiring CDI. The results of fecal leukocyte
      examinations were positive in 33 (27%) patients. The overall in-hospital
      mortality rate was 26.2%. There were no significant differences between patients
      with nontoxigenic CDI and patients with toxigenic CDI. CONCLUSION: Clostridium
      difficile infection can develop in healthcare facilities and in community
      settings, especially in immunocompromised patients.

PMID- 23978491
TI  - The yin and the yang of follicular lymphoma cell niches: role of microenvironment
      heterogeneity and plasticity.
AB  - Follicular lymphoma (FL) results from the malignant transformation of germinal
      center B cells and is characterized by recurrent genetic alterations providing a
      direct growth advantage or facilitating interaction with tumor microenvironment.
      In agreement, accumulating evidences suggest a dynamic bidirectional crosstalk
      between FL B cells and surrounding non-malignant cells within specialized tumor
      niches in both invaded lymph nodes and bone marrow. Infiltrating stromal cells,
      macrophages, and T/NK cell subsets either contribute to anti-tumor immune
      response, or conversely form a tumor supportive network promoting FL B cell
      survival, growth, and drug resistance. This review depicts the phenotypic
      heterogeneity and functional plasticity of the most important FL cell partners
      and describes their complex interplay. We also unravel how malignant B cells
      recruit and subvert accessory immune and stromal cells to trigger their
      polarization toward a supportive phenotype. Based on these observations,
      innovative therapeutic approaches have been recently proposed, in order to
      benefit from local anti-tumor immunity and/or to selectively target the
      protective cell niche. 

PMID- 23978492
TI  - Raman spectroscopy demonstrates prolonged alteration of bone chemical composition
      following extremity localized irradiation.
AB  - INTRODUCTION: Radiotherapy to the appendicular skeleton can cause an increased
      risk of developing catastrophic fractures with delayed bone healing or non-union,
      and may subsequently require multiple procedures and amputation. Biomechanical
      studies suggest that irradiated bone is more brittle, but the cause is unclear
      and cannot be explained by changes to bone structure or quantity, suggesting that
      there are crucial changes in irradiated bone material properties. Raman
      spectroscopy provides a means to assess the chemical properties of the mineral
      and matrix constituents of bone, which could help explain post-radiation
      embrittlement. In this study we use a murine tibial model with focal irradiation
      and perform Raman spectroscopy to test the hypothesis that changes in bone
      chemistry following irradiation is consistent with reduced bone quality and
      persists in the long term after irradiation. METHODS: Female BALB/F mice aged
      12weeks were subjected to unilateral, localized hindlimb irradiation in 4 daily
      5Gy fractions (4*5Gy) totaling 20Gy, and were euthanized at 1, 4, 8, 12, and
      26weeks post-irradiation (n=6/group). The irradiated (right) and non-irradiated
      contralateral control (left) tibiae were explanted and assessed by non-polarized
      and polarized Raman spectroscopy over the proximal cortical bone surface. Raman
      parameters used included the mineral/matrix ratio, mineral crystallinity,
      carbonate/phosphate ratio, collagen cross-link ratio, and depolarization ratio.
      RESULTS: Significantly increased collagen cross-link ratio and decreased
      depolarization ratio of matrix were evident at 1week after irradiation and this
      persisted through 26weeks. A similar significant decrease was observed for
      depolarization ratio of mineral at all time points except 8 and 26weeks. At
      4weeks after irradiation there was a significantly increased mineral/matrix
      ratio, increased mineral crystallinity, and decreased carbonate/phosphate ratio
      compared to controls. However, at 12weeks after irradiation these parameters had
      moved in the opposite direction, resulting in a significantly decreased
      mineral/matrix ratio, decreased crystallinity and increased carbonate/phosphate
      ratio compared to controls. At 26weeks, mineral/matrix, crystallinity and
      carbonate/phosphate ratios had returned to normal. DISCUSSION: In this mouse
      model, Raman spectroscopy reports both bone mineral and collagen cross-link
      radiation-induced abnormalities that are evident as early as one week after
      irradiation and persists for 26weeks. The picture is one of extensive damage,
      after which there is an attempt at remodeling. We hypothesize that pathological
      cross-links formed by radiation damage to collagen are poorly resorbed during the
      altered remodeling process, so that new tissue is formed on a defective scaffold,
      resulting in increased bone brittleness.

PMID- 23978493
TI  - Plasma anti-Mullerian hormone as a biomarker for bovine granulosa-theca cell
      tumors: comparison with immunoreactive inhibin and ovarian steroid
      concentrations.
AB  - Granulosa-theca cell tumors (GTCTs) are the most frequently reported ovarian
      tumors in cattle. Clinically, GTCTs could be confused with other ovarian
      abnormalities; therefore, the only definitive diagnosis for such tumors is
      histopathology of a biopsy from the affected ovary. However, this is an invasive
      technique and unsuitable for farm conditions. As a result, the key aim of this
      study was to evaluate the diagnostic value of anti-Mullerian hormone (AMH), a
      glycoprotein hormone that is synthesized exclusively by ovarian granulosa cells,
      as a sensitive noninvasive biomarker for diagnosing GTCTs in cattle. To achieve
      this aim, we conducted two experiments. In experiment 1, four clinically healthy
      Japanese Black cows had blood samples taken daily over one estrous cycle to
      characterize their AMH profiles throughout the estrous cycle. Additionally,
      single blood samples were collected from 21 cyclic cows to clarify the
      physiological range of AMH. In experiment 2, cows with histologically confirmed
      GTCT (GTCT group, n = 9) and cows affected with cystic ovarian disease (COD
      group, n = 8) had one blood sample taken before extraction of the tumorous ovary
      or therapeutic treatment for the COD. Blood samples (n = 105) from cyclic cows (n
      = 25) in experiment 1 were assigned as a physiologically cyclic group (PC group).
      Plasma AMH, immunoreactive inhibin (ir-INH), estradiol-17beta (E2), testosterone
      (T), and progesterone (P4) concentrations were assayed in all samples. In
      experiment 1, the mean plasma AMH concentration was 0.09 +/- 0.003 ng/mL and did
      not show substantial fluctuation throughout the estrous cycle. In experiment 2,
      plasma AMH, ir-INH, and E2 concentrations were significantly elevated in the GTCT
      group in comparison with the PC group; among these parameters, only the AMH
      concentrations were significantly higher in the GTCT group than in the COD group.
      The area under the receiver operating characteristic curve of AMH for diagnosis
      of GTCT was 0.99 and was significantly higher than that of ir-INH (P < 0.001) and
      E2 (P < 0.01). Moreover, the AMH at a cutoff point of >=0.36 ng/mL had the
      highest diagnostic accuracy (99.2%), sensitivity (100%), and specificity (99.1%)
      compared with the other tested parameters. In conclusion, plasma AMH
      concentration is probably a more reliable and sensitive biomarker for bovine
      GTCTs than the concentrations of ir-INH or ovarian steroids. 

PMID- 23978494
TI  - Malignant transformation of superficial peritoneal endometriosis lesion.
AB  - A 63-year-old woman with no medical history underwent an abdominal surgery with
      hysterectomy and bilateral salpingo-oophorectomy for a 10 cm peritoneal cyst with
      increased cancer antigene-125. A large suspicious tumour of the Douglas space,
      with contact to the uterus and the rectal wall was described. The rest of the
      exploration was normal, specially the rest of the peritoneum. Histopathology
      revealed a malignant transformation of a superficial peritoneal endometriosis.
      Secondary surgery was thus completed by laparoscopy with bilateral pelvic and
      para-aortic lymph node dissections, omentectomy and multiple peritoneal biopsies.
      All staging samples were free of cancer; therefore no complementary therapy was
      administered. After 18 months of follow-up, consisting of clinical examination
      and pelvis magnetic resonance imaging every 6 months, we did not observe any
      recurrence. Malignant transformation of superficial peritoneal endometriosis is a
      rare disease and surgical management seems to be the main treatment. 

PMID- 23978495
TI  - Small bowel metastasis of uterine cervical adenocarcinoma.
AB  - A few cases of small bowel metastasis from uterine cervical cancer have been
      previously reported. All reported cases were connected to squamous cell
      carcinoma, while none were associated with cervical adenocarcinoma. This report
      is of a rare case of cervical adenocarcinoma that haematogenously metastasised to
      the small intestine, and which caused a perforation and small bowel obstruction
      metachronously. An 84-year-old woman was admitted to our hospital with vaginal
      bleeding. She was diagnosed with FIGO stage III cervical adenocarcinoma by
      imaging and pathohistological examinations. Three months after receiving
      radiation therapy to control the bleeding, surgery was performed twice; the first
      operation for small bowel perforation and the second for small bowel obstruction.
      She was then diagnosed with haematogenous metastasis of cervical adenocarcinoma
      to the ileum according to the operative, histopathological and immunopathological
      findings. 

PMID- 23978496
TI  - Bizarre cause for avulsion of permanent maxillary lateral incisor tooth.
AB  - A 9-year-old boy presented with a missing upper front tooth after an accident
      involving kite flying. Diagnosis of avulsion of the upper right lateral incisor
      (22) was made after examination of his socket as well as by radiological
      investigations. A removable partial denture was given for the aesthetic purpose.
      The patient is under follow-up. The present case illustrates the management of
      avulsion. 

PMID- 23978497
TI  - Pneumosinus dilatans multiplex associated with hormonal imbalance.
AB  - Pneumosinus dilatans describes an abnormal dilation of one or more paranasal
      sinuses without radiological evidence of localised bone destruction, hyperostosis
      or mucous membrane thickening. Dilation of mastoid air cells also occurs rarely
      along with involvement of paranasal sinuses. This rare combination of unknown
      aetiology was reported in two cases in the literature and termed 'Pneumosinus
      Dilatans Multiplex' (PSDM). It is usually asymptomatic, and is detected
      incidentally on plain radiography, CT or MRI. If left untreated, it can further
      erode the bone leading to complications such as facial asymmetry, neurological
      disorders and pathological fractures. The aetiology of the condition remains
      obscure. Various hypotheses proposed are the presence of gas-forming
      microorganisms, spontaneous drainage of a mucocele, the presence of a one-way
      valve, dysregulation of hormonal levels leading to a disturbance of osteoblastic
      and osteoclastic activity. This paper describes a case of PSDM possibly secondary
      to hormonal disturbance. 

PMID- 23978498
TI  - Corticosteroid responsive prolonged thrombocytopenia in a case of dengue fever.
AB  - Thrombocytopenia and bleeding manifestations are consistent features of dengue
      fever. Usually thrombocytopenia resolves and platelet count normalises by day 10
      of fever. Persistent thrombocytopenia is not a feature of dengue fever. Proposed
      mechanisms behind thrombocytopenia are many. Direct platelet destruction by
      dengue virus, immune-mediated platelet destruction and even megakaryocytic immune
      injury have been proposed as underlying mechanisms. We are reporting a case of an
      old man who presented in dengue season in 2012 with fever and bleeding and was
      diagnosed as a case of dengue fever. He developed persistent thrombocytopenia
      requiring treatment on the lines of immune thrombocytopenia and responded to
      steroids. Other causes of thrombocytopenia were ruled out. 

PMID- 23978499
TI  - Unusual aetiology of isolated lower motor neuron facial palsy: systemic lupus
      erythematosus presenting with cranial nerve palsy and nephritis.
AB  - A 20-year-old woman presented with common cold symptoms was found to have a left
      sided facial droop. On examination, peripheral facial nerve palsy was confirmed.
      Subsequent testing showed nephrotic range proteinuria and positive serologies
      including antinuclear antibody and anti-smith antibody. Kidney biopsy showed
      stage III lupus nephritis. Treatment with pulse steroids along with mycophenolate
      mofetil for her lupus nephritis resulted in concomitant improvement of her facial
      palsy. 

PMID- 23978500
TI  - Endoscopy unit efficiency: quality redefined.

PMID- 23978502
TI  - Strain-dependent effects of long-term treatment with melatonin on kainic acid
      induced status epilepticus, oxidative stress and the expression of heat shock
      proteins.
AB  - Oxidative stress is implicated in the pathogenesis of both hypertension and
      epileptogenesis, therefore it could be used as a tool for studying co-morbidity
      of hypertension and epilepsy. Clinical data suggest that melatonin is a potent
      antioxidant that is effective in the adjunctive therapy of hypertension and
      neurodegenerative diseases. The present study aimed to explore and compare the
      efficacy of chronic pretreatment with melatonin infused via subcutaneous osmotic
      mini-pumps for 14 days (10 mg/kg per day) on kainic acid (KA)-induced status
      epilepticus, oxidative stress and expression of heat shock protein (HSP) 72 in
      spontaneously hypertensive rats (SHRs) and normotensive Wistar rats. SHRs showed
      higher lipid peroxidation (LP) in the frontal cortex and hippocampus and
      decreased cytosolic superoxide dismutase (SOD/CuZn) production in the frontal
      cortex compared to Wistar rats. Status epilepticus (SE) induced by KA (12 mg/kg,
      i.p.) was accompanied by increased LP and expression of HSP 72 in the hippocampus
      of the two strains and increased SOD/CuZn production in the frontal cortex of
      SHRs. Melatonin failed to suppress seizure incidence and intensity though the
      latency for seizure onset was significantly increased in SHRs. Melatonin
      attenuated the KA-induced increase in the level of LP in the hippocampus both in
      SHRs and Wistar rats. However, an increased activity in SOD/CuZn and
      mitochondrial SOD Mn as well as reduced expression of HSP 72 in the hippocampus
      was observed only in Wistar rats pretreated with melatonin. Taken together, the
      observed strain differences in the efficacy of chronic melatonin exposure before
      SE suggest a lack of a direct link between the seizure activity and the markers
      of oxidative stress and neurotoxicity.

PMID- 23978503
TI  - An analysis of the indications for cesarean section in a teaching hospital in
      China.
AB  - OBJECTIVES: Cesarean delivery rates have increased remarkably worldwide. The
      indications for this increase are not fully understood and there may be regional,
      ethnic or health system differences in quoted indications which may explain, at
      least in part, the observed changes. In 2008 China was cited as having one of the
      highest rates of cesarean delivery in the world, but there was no accurate
      information about the indications for the high rate. This study sought to provide
      some information about the high cesarean section rate in China. STUDY DESIGN:
      Data on all births in a university teaching hospital in northern China serving a
      general obstetric population, excluding premature births, were collected from the
      hospital database from January 2009 to September 2012. All indications on the
      mode of delivery were analyzed for live births. RESULTS: There were 5267 births
      and the cesarean delivery rate was 41.4% in the study period. There was no
      significant trend in the cesarean delivery rate from 2009 to 2012. Fetal
      indications contributed most to the rate. More than 50% of all cesarean
      deliveries were due to nuchal cord, previous cesarean delivery, fetal distress
      and malpresentation. The rate of cesarean delivery on maternal request was 9.07%.
      Smaller contributions to the indications for cesarean delivery came from
      cephalopelvic disproportion, preeclampsia, prolonged labor, uterine rupture and
      other obstetric conditions. CONCLUSION: The data show increased fetal or maternal
      risk assessments are the main indications for cesarean delivery rather than
      cesarean delivery on maternal request in China.

PMID- 23978504
TI  - Transporters and receptors for short-chain fatty acids as the molecular link
      between colonic bacteria and the host.
AB  - The mutually beneficial relationship between colonic bacteria and the host has
      been recognized but the molecular aspects of the relationship remain poorly
      understood. Dietary fiber is critical to this relationship. The short-chain fatty
      acids acetate, propionate and butyrate, generated by bacterial fermentation of
      dietary fiber, serve as messengers between colonic bacteria and the host. The
      beneficial effects of these bacterial metabolites in colon include, but are not
      limited to, suppression of inflammation and prevention of cancer. Recent studies
      have identified the plasma membrane transporter SLC5A8 and the cell-surface
      receptors GPR109A and GPR43 as essential for the biologic effects of short-chain
      fatty acids in colon. These three proteins coded by the host genome provide the
      molecular link between colonic bacteria and the host. 

PMID- 23978501
TI  - The neural and genetic basis of executive function: attention, cognitive
      flexibility, and response inhibition.
AB  - Executive function is a collection of cognitive processes essential for higher
      order mental function. Processes involved in executive function include, but are
      not limited to, working memory, attention, cognitive flexibility, and impulse
      control. These complex behaviors are largely mediated by prefrontal cortical
      function but are modulated by dopaminergic, noradrenergic, serotonergic, and
      cholinergic input. The ability of these neurotransmitter systems to modulate
      executive function allows for adaptation in cognitive behavior in response to
      changes in the environment. Because of the important role these neurotransmitter
      systems play in regulating executive function, changes in these systems can also
      have a grave impact on executive function. In addition, polymorphisms in genes
      associated with these neurotransmitters are associated with phenotypic
      differences in executive function. Understanding how these naturally occurring
      polymorphisms contribute to different executive function phenotypes will advance
      basic knowledge of cognition and potentially further understanding and treatment
      of mental illness that involve changes in executive function. In this review, we
      will examine the influence of dopamine, norepinephrine, serotonin, and
      acetylcholine on the following measures of executive function: attention,
      cognitive flexibility, and impulse control. We will also review the effects of
      polymorphisms in genes associated with these neurotransmitter systems on these
      measures of executive function. 

PMID- 23978505
TI  - Developmentally and culturally appropriate screening in primary care: development
      of the behavioral health checklist.
AB  - OBJECTIVE: To evaluate the construct validity of the Behavioral Health Checklist
      (BHCL) for children aged from 4 to 12 years from diverse backgrounds. METHOD: The
      parents of 4-12-year-old children completed the BHCL in urban and suburban
      primary care practices affiliated with a tertiary-care children's hospital.
      Across practices, 1,702 were eligible and 1,406 (82.6%) provided consent.
      Children of participating parents were primarily non-Hispanic black/African
      American and white/Caucasian from low- to middle-income groups. Confirmatory
      factor analyses examined model fit for the total sample and subsamples defined by
      demographic characteristics. RESULTS: The findings supported the hypothesized 3
      factor structure: Internalizing Problems, Externalizing Problems, and
      Inattention/Hyperactivity. The model demonstrated adequate to good fit across age
      groups, gender, races, income groups, and suburban versus urban practices.
      CONCLUSION: The findings provide strong evidence of the construct validity,
      developmental appropriateness, and cultural sensitivity of the BHCL when used for
      screening in primary care.

PMID- 23978506
TI  - Laboratory practice guidelines for detecting and reporting JAK2 and MPL mutations
      in myeloproliferative neoplasms: a report of the Association for Molecular
      Pathology.
AB  - Recurrent mutations in JAK2 and MPL genes are genetic hallmarks of BCR-ABL1
      negative myeloproliferative neoplasms. Detection of JAK2 and MPL mutations has
      been incorporated into routine diagnostic algorithms for these diseases. This
      Special Article summarizes results from a nationwide laboratory survey of JAK2
      and MPL mutation analysis. Based on the current practice pattern and the
      literature, this Special Article provides recommendations and guidelines for
      laboratory practice for detection of mutations in the JAK2 and MPL genes,
      including clinical manifestations for prompting the mutation analysis, current
      and recommended methodologies for testing the mutations, and standardization for
      reporting the test results. This Special Article also points to future directions
      for genomic testing in BCR-ABL1-negative myeloproliferative neoplasms. 

PMID- 23978507
TI  - A search for novel thermoluminescent radiation dosimeter media.
AB  - We describe two example pilot efforts to help define new thermoluminescent
      dosimeter media. The first concerns ZnS:Mn nanophosphors, prepared by chemical
      precipitation using zinc and sodium sulfate, doped with manganese sulfate at
      concentrations varying from 1 to 3mol. The second concerns chemical vapor
      deposited diamond, produced as a thin film or as amorphous carbon on a single
      crystal silicon substrate, each deposited under the same conditions, use being
      made of the hot filament-chemical vapor deposition (HFCVD) technique. The gas
      concentrations used were 1% CH4 in 99% H2 and 25% CH4 in 75% H2. Characterization
      of formations used FESEM, XRD and EDX. The nanophosphors consisted of particles
      of sizes in the range 85-150nm, the thermoluminescence (TL)-based radiation
      detection medium giving rise to a single peaked glow curve of maximum yield at a
      temperature of 250 degrees C at a heating rate of 5 degrees C/s. The TL response
      increased linearly with radiation dose, ZnS doped to 2mol of Mn being found the
      most sensitive. Regarding chemical vapor deposited (CVD) carbon, inappreciable TL
      was found for the resultant ball-like amorphous carbon films, graphite, and the
      silicon substrate, whereas CVD diamond films showed a promising degree of
      linearity with dose. For both the ZnS and diamond samples, TL signal fading was
      appreciable, being some 40% per day for ZnS and>50% per day for CVD films even
      under storage in the dark at room temperature, making it apparent that there is
      need to adjust parameters such as the size of nanoparticles. 

PMID- 23978508
TI  - Response of ionization chamber based pocket dosimeter to beta radiation.
AB  - Quantitative estimate of the response of ionization chamber based pocket
      dosimeters (DRDs) to various beta sources was performed. It has been established
      that the ionization chamber based pocket dosimeters do not respond to beta
      particles having energy (Emax)<1 MeV and same was verified using (147)Pm, (85)Kr
      and (204)Tl beta sources. However, for beta particles having energy >1 MeV, the
      DRDs exhibit measureable response and the values are ~8%, ~14% and ~27% per mSv
      for natural uranium, (90)Sr/(90)Y and (106)Ru/(106)Rh beta sources respectively.
      As the energy of the beta particles increases, the response also increases. The
      response of DRDs to beta particles having energy>1 MeV arises due to the fact
      that the thickness of the chamber walls is less than the maximum range of beta
      particles. This may also be one of the reasons for disparity between doses
      measured with passive/legal dosimeters (TLDs) and DRDs in those situations in
      which radiation workers are exposed to mixed field of gamma photons and beta
      particles especially at uranium processing plants, nuclear (power and research)
      reactors, waste management facilities and fuel reprocessing plants etc. The paper
      provides the reason (technical) for disparity between the doses recorded by TLDs
      and DRDs in mixed field of photons and beta particles.

PMID- 23978509
TI  - Effect of population selection on 99th percentile values for a high sensitivity
      cardiac troponin I and T assays.
AB  - OBJECTIVE: Using objective laboratory and clinical criteria to more accurately
      determine the 99th percentile values for cardiac troponin I and T. DESIGN AND
      METHODS: We measured cardiac troponin T and cardiac troponin I with high
      sensitivity assays in a large cohort of apparently healthy community subjects and
      calculated 99th percentiles for different sexes and ages. Subjects with possible
      subclinical disease were eliminated based on objective laboratory criteria, eGFR
      and NT-proBNP, and clinical criteria, history and examination and echocardiogram.
      RESULTS: For men and women of all ages, separately, more than 50% of subjects
      were excluded using these criteria, with a lesser proportion of younger subjects
      being excluded. In men aged <75 years, the 99th percentile for cTnI decreased by
      more than 50% from 22.9 ng/L to 10.3 ng/L. In other age groups and for cTnT the
      decrease was smaller (%) but still considerable. CONCLUSIONS: For establishing
      cardiac troponin 99th percentiles, simply using self-reporting of health is
      insufficient. Objective laboratory measures and clinical and echocardiographic
      assessments are essential to define a healthy population, especially in older
      persons.

PMID- 23978510
TI  - Paradox effects of kynurenines on LTP induction in the Wistar rat. An in vivo
      study.
AB  - Kynurenic acid (KYNA), a neuroactive metabolite of tryptophan that acts on
      different receptors (e.g. those of N-methyl-D-aspartate (NMDA) and presynaptic
      alpha7 nicotinic acetylcholine (nACh)), exerts fundamentally antiglutamatergic
      effects. In view of its antiglutamatergic properties, an elevation of the KYNA
      level within the brain might result in neuroprotection. However, the use of KYNA
      as a neuroprotective agent is rather limited, because it crosses the blood-brain
      barrier (BBB) to only a poor extent. During recent years, new KYNA derivatives
      have been developed which can readily traverse the BBB and also exert
      neuroprotection. However, as KYNA and its derivatives are able to interfere with
      glutamatergic and cholinergic transmission, the potential risks of interfering
      with cognitive functions cannot be excluded. This in vivo study on anesthetized
      rats therefore tested the effects of the administration of KYNA and a KYNA
      derivative (SZR72) (in a dosage that exerted neuroprotection) on long-term
      potentiation (LTP) and pure field excitatory postsynaptic potentials induced by
      contralateral CA3 region stimulation and recorded in the pyramidal layer of the
      CA1 region of the hippocampus. Surprisingly, KYNA and this derivative did not
      reduce, but rather increased the induceability of LTP. The possible explanation
      is discussed in detail. In brief: an elevated KYNA level in the perisynaptic area
      produced, for example, by exogenous prodrug or derivative administration exerts
      preferential effects on the extrasynaptic NMDA receptors and the nACh receptors
      on presynaptic glutamatergic terminals, while sparing the currents mediated by
      synaptic NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid
      receptors. This might be the explanation why the treatment with the prodrug of
      KYNA or the KYNA derivative in a dosage which induced neuroprotection did not
      reduce the cognitive functions or the LTP.

PMID- 23978511
TI  - Axon guidance effect of classical morphogens Shh and BMP7 in the hypothalamo
      pituitary system.
AB  - Hypothalamus plays a key role in homeostasis, and functions of the hypothalamus
      depend on the accurate trajectory of hypothalamic neuroendocrine axons. Thus,
      understanding the guidance of hypothalamic neuroendocrine axons is crucial for
      knowing how hypothalamus works. Previous studies suggest FGF10 deriving from the
      medial ventral midline of the hypothalamus plays an important role in axon
      guidance of the developing hypothalamus. Here we show that Shh and BMP7, which
      are from the anterior and posterior hypothalamic ventral midline respectively,
      together repel hypothalamic axons towards the medial ventral midline. 

PMID- 23978512
TI  - Group I metabotropic glutamate receptors modulate late phase long-term
      potentiation in hippocampal CA1 pyramidal neurons: comparison of apical and basal
      dendrites.
AB  - The hippocampal long-term potentiation (LTP) at Schaffer collateral synapses onto
      CA1 pyramidal neurons has been widely studied as a cellular model of activity
      dependent enhancement of synaptic transmission. The apical (stratum radiatum) and
      basal dendrites (stratum oriens) of hippocampal CA1 pyramidal neurons differ in
      LTP induction and maintenance. Here, the role of mGlu receptors in the induction
      and maintenance of late-LTP was investigated, in comparison of these two
      compartments. My results show that mGlu1 receptor modulates late-LTP in apical
      dendrites and basal dendrites, whereas mGlu5 receptor modulates late-LTP only in
      apical dendrites. 

PMID- 23978513
TI  - Inhibitory theta burst stimulation of affected hemisphere in chronic stroke: a
      proof of principle, sham-controlled study.
AB  - Non-invasive brain stimulation is presently being tested as a potential
      therapeutic intervention for stroke rehabilitation. Following a model of
      competitive interactions between the hemispheres, these interventions aim to
      increase the plasticity of stroke hemisphere by applying either excitatory
      protocols to the damaged hemisphere or inhibitory protocols to the non-stroke
      hemisphere. Here we test the safety and feasibility of using an inhibitory
      protocol on the stroke hemisphere to improve the response to conventional therapy
      via a homeostatic increase in learning capacity. Twelve chronic stroke patients
      received TBS to stroke hemisphere (6 patients inhibitory TBS and 6 sham TBS)
      followed by physical therapy daily for 10 working days. Patients and therapists
      were blinded to the type of TBS. Action Research Arm Test (ARAT), Nine-Hole
      Pegboard Test (NHPT) and Jebsen-Taylor Test (JTT) were the primary outcome
      measures, grip and pinch-grip dynamometry were the secondary outcome measures.
      All patients improved ARAT and JTT scores for up to 3 months post-treatment. ARAT
      scores improved significantly in both real and sham groups, but only patients
      receiving real TBS significantly improved on the JTT: 3 months post-treatment
      mean execution time was reduced compared to baseline by 141 s for real group and
      by 65s for the sham group. This small exploratory study suggests that
      ipsilesional inhibitory TBS is safe and that it has the potential to be used in a
      larger trial to enhance the gain from a late rehabilitation program in chronic
      stroke patients.

PMID- 23978514
TI  - Investigating redox regulation of protein tyrosine phosphatases using low pH
      thiol labeling and enrichment strategies coupled to MALDI-TOF mass spectrometry.
AB  - A central feature of the protein tyrosine phosphatase (PTP) catalytic mechanism
      is an attack of the substrate's phosphate moiety by a thiolate ion in the
      signature CX5R motif. In addition to being an effective nucleophile in this form,
      the thiolate ion is also susceptible to reversible redox regulation. This
      attribute permits temporal inhibition of PTP activities, which affects numerous
      cellular processes utilizing kinase-mediated signal propagation. Accumulating
      evidence has revealed diverse mechanisms adopted by PTPs to avoid irreversible
      thiol oxidation of the active site Cys residue, often involving structurally
      proximal thiols within the active site region. Therefore, there has been a
      significant effort made to develop thiol labeling strategies coupled to mass
      spectrometry to identify and characterize redox sensitive thiols within PTPs as a
      necessary step in understanding how a particular PTP is regulated by redox
      signaling. A common drawback to many current methods is the use of neutral pH
      labeling techniques, requiring special attention with regards to non-specific
      thiol oxidation during sample preparation. This study describes the use of rapid,
      low pH thiol labeling methods to overcome this issue. Mercury immobilized metal
      affinity chromatography (Hg-IMAC) demonstrated high selectivity and specificity
      while enriching for thiol-containing peptides from the atypical dual specificity
      phosphatase hYVH1 (also known as DUSP12). This approach revealed several
      reversibly oxidized thiols within the catalytic domain of hYVH1. Subsequently,
      use of another low pH labeling reagent, 4,4-dithiopyridine (4-DTP) helped
      identify novel disulfide linkages providing evidence that hYVH1 utilizes a
      disulfide exchange mechanism to prevent irreversible oxidation of the catalytic
      Cys residue in the active site. 

PMID- 23978515
TI  - Visual optical biosensors based on DNA-functionalized polyacrylamide hydrogels.
AB  - Biosensors are devices that can provide quantitative or semi-quantitative
      analytical information about target molecules, where molecular recognition is
      based on biomolecular interactions. In recent years, DNA has emerged as a useful
      molecule for biosensor development since DNA can not only recognize its
      complementary strand, but also metal ions, small molecules, proteins and cells
      utilizing DNA aptamer technology. Converting DNA binding events into useful
      biosensors often require sensor immobilization. Among the various materials for
      sensor immobilization, hydrogels are particularly attractive. Hydrogels are
      crosslinked hydrophilic polymer networks that undergo swelling in water. In a
      gel, DNA immobilization can take place in 3D, allowing for high DNA loading
      capacity. Hydrogels are transparent, offering low optical background. The gel
      volume is affected by many environmental parameters such as temperature, pH,
      ionic strength, and solvent composition. In this paper, we present a concise
      summary of recent developments in DNA-functionalized hydrogel biosensors for
      visual detection. Detailed methods for immobilizing DNA biosensors in monolithic
      polyacrylamide gels and gel microparticles are supplied. 

PMID- 23978517
TI  - Corneal regeneration by transplantation of corneal epithelial cell sheets
      fabricated with automated cell culture system in rabbit model.
AB  - We have performed clinical applications of cell sheet-based regenerative medicine
      with human patients in several fields. In order to achieve the mass production of
      transplantable cell sheets, we have developed automated cell culture systems.
      Here, we report an automated robotic system utilizing a cell culture vessel, cell
      cartridge. The cell cartridge had two rooms for epithelial cells and feeder layer
      cells separating by porous membrane on which a temperature-responsive polymer was
      covalently immobilized. After pouring cells into this robotic system, cell
      seeding, medium change, and microscopic examination during culture were
      automatically performed according to the computer program. Transplantable corneal
      epithelial cell sheets were successfully fabricated in cell cartridges with this
      robotic system. Then, fabricated cell sheets were transplanted onto ocular
      surfaces of rabbit limbal epithelial stem cell deficiency model after 6-h
      transportation using a portable homothermal container to keep inner temperature
      at 36  degrees C. Within one week after transplantation, normal corneal
      epithelium was successfully regenerated. This automatic cell culture system would
      be useful for industrialization of tissue-engineered products for regenerative
      medicine.

PMID- 23978516
TI  - Post-infectious glomerulonephritis with nephrotic syndrome secondary to rotavirus
      infection.

PMID- 23978518
TI  - The use of laryngeal mucosa mesenchymal stem cells for the repair the vocal fold
      injury.
AB  - Stem cell transplantation is a kind of attractive and new approach that
      complements traditional restorative or surgical techniques for the regeneration
      of injured or pathologically damaged laryngeal tissues. However, the best cell
      delivery strategy remains to be identified. The objective of this study was to
      establish a new strategy to the healing of injured vocal fold, using laryngeal
      mucosa mesenchymal stem cells differentiating into myofibroblasts or fibroblasts
      and improving the reconstruction microenvironment in the vocal fold injury as a
      new alternative as seed cells for laryngeal tissue engineering. After isolation
      and expansion, cells were identified as adherent mesenchymal cells with
      substantial proliferation potential in vitro, and were also characterized by flow
      cytometry. The differentiation potential of mesenchymal cells was maintained
      during proliferation as confirmed by culturing for adipogenesis, osteogenesis and
      chondrocyte. When LM-MSC was transplanted into the injured vocal fold, it has the
      potent differentiated into myofibroblasts and fibroblasts, which could regulate
      extracellular matrix, block collagen and the fibronectin rapid increased, inhibit
      the rapidly decrease of elastic fiber and HA, decrease the microenvironment
      inflammatory reaction, and prevent the formation of vocal fold scar.

PMID- 23978519
TI  - Breast cancer personalized medicine: challenges and opportunities.

PMID- 23978520
TI  - miR-21-containing microvesicles from injured tubular epithelial cells promote
      tubular phenotype transition by targeting PTEN protein.
AB  - Renal fibrosis is inevitably progressive no matter what the initial insult is or
      whether the insult persists. In an experimental fibrosis model induced by
      unilateral ureteral obstruction, the accelerated pathological changes could
      hardly be explained by aggravated pressure caused by hydronephrosis after
      ligation. Moreover, at the initial stage, tubular phenotype transition and matrix
      deposition in obstructive kidneys are always local and scattered; however, these
      renal lesions expand and progress with time. In this study, cultured recipient
      tubular cells underwent phenotype transition after incubation with conditioned
      media derived from transforming growth factor-beta1-treated donor tubular cells.
      Thus, it is reasonable to speculate that some secretable molecules from injured
      tubules contribute to the progression of renal fibrosis. Herein, we report that
      secreted miRNA-21 (miR-21) can serve as the molecule mediating intercellular
      communication. miR-21 was packaged into microvesicles, which enter and deliver
      miR-21 into recipient tubular cells, and exogenous miR-21 enhances Akt signaling
      by target depression of phosphatase and tensin homolog (PTEN) protein, and
      promotes tubular phenotype transition. These results demonstrate that tubular
      cells can secrete miR-21 and deliver it into recipient tubules by microvesicles,
      where the exogenous miR-21 can target PTEN protein and enhance Akt signaling in
      recipient cells. Microvesicle-mediated delivery of miR-21 among tubular
      epithelial cells might shed new light on the mechanism of progressive renal
      fibrosis.

PMID- 23978521
TI  - Persistent left superior vena cava draining into the left atrium.
AB  - A 40-year-old man was admitted with necrotising fasciitis of the right thigh.
      Further workup to evaluate for an infectious source revealed an incidental
      finding of persistent left superior vena cava via transesophageal
      echocardiography. This finding was confirmed by cardiac MRI. During his
      hospitalisation, he also developed altered mental status which was found to be
      secondary to systemic emboli by a head MRI. The primary source of infection was
      likely his dental abscesses. He underwent intravenous antibiotic therapy for a
      total of 6 weeks and was then referred to a specialised vascular centre for
      further management of his congenital anomaly. 

PMID- 23978522
TI  - Spatio-temporal variations of black carbon concentrations in the Megacity
      Beijing.
AB  - The spatial and temporal distribution and the flux of black carbon (BC)
      concentration in Beijing were continuously investigated over a two-year period at
      five sites to highlight the relative influence of contributing sources. The
      results demonstrate firstly that there is significant spatio-temporal variability
      of BC in Beijing. Highest concentrations occurred during winter primarily due to
      stagnant meteorological conditions, and seasonal BC sources, such as coal
      combustion for heating purposes. Biomass burning was identified as a minor
      seasonal source during the summer months. BC also varied spatially with higher
      concentrations in the SE of Beijing and lower concentrations in the NW, due to
      the differing emission intensity of various local BC sources such as traffic and
      industry. Frequently, overnight BC concentrations were higher due to specific
      meteorological conditions, such as the lower urban mixing layer height and
      various anthropogenic activities, such as exclusive night-time heavy duty vehicle
      traffic in the inner-city. 

PMID- 23978523
TI  - Association between state physical education (PE) requirements and PE
      participation, physical activity, and body mass index change.
AB  - OBJECTIVE: To determine if state physical education (PE) laws are associated with
      student physical education attendance and physical activity (PA), and whether
      physical education and competitive food laws, in conjunction, are associated with
      lower BMI change. METHOD: State laws regarding physical education time
      requirements and competitive foods in 2003 and 2006 were classified as strong,
      weak, or none, based on codified law ratings obtained from the Classification of
      Laws Associated with School Students. Laws were linked to student data on PE
      attendance and physical activity (8th grade, Spring 2007) and BMI change (5th-8th
      grade, 2004-2007), obtained from the Early Childhood Longitudinal Study (n=5510
      students in 40 states). RESULTS: Girls reported 0.31 more days of activity (95%
      CI: 0.02, 0.61) and were more likely to attend physical education >= 3 days/week
      (74.1% versus 52.1%, difference=22.0, 95% CI: 2.1, 42.0) if they resided in
      states with strong physical education laws compared to no physical education
      laws. Weak physical education laws had modest associations with PE and activity,
      and there was no evidence that weak laws reduce BMI gain regardless of
      competitive food laws. CONCLUSION: Strong physical education laws with specific
      time requirements may increase physical education attendance and activity in
      girls. There is insufficient evidence that physical education laws reduce student
      weight gain.

PMID- 23978524
TI  - Weakly positive tests and chronologic variation of the QuantiFERON assay: a
      retrospective appraisal of usefulness.
AB  - OBJECTIVES: QuantiFERON Tb Gold IT (QFT) is routinely used as diagnostic tool for
      detecting immune reactivity towards Mycobacterium tuberculosis. When diagnosing a
      latent infection weakly positive results and test reproducibility must be
      considered. PURPOSE: To judge the frequency of useful information versus
      confusion gained by QFT in patients with immune-mediated diseases and in
      pulmonary outpatients. METHODS: We retrospectively analysed 1485 QFT-tests
      performed on 855 patients with autoimmune diseases prior to initiating biologics
      and on 447 pulmonary outpatients with a suspected tuberculosis infection over a
      period of 16 months. In 161 cases the IGRA test was erroneously repeated. After
      18 months clinical, radiographic and bacteriologic evidence for tuberculosis was
      collected. RESULTS: Of all 1485 QFT-tests 247 (=16.63%) showed a positive result,
      1186 (79.87%) were negative and 52 (3.50%) turned out to be indeterminate. Using
      the manufacturers cut-off value for the interferon-gamma response, a cohort (n =
      64) of weakly positive individuals (26% of all positives) was apparent. Repeated
      testing within ten weeks yielded negative reactivity in 69% of these patients. Of
      25 IGRA positive patients who had a repeat test after one year without
      tuberculosis medication, 48% showed a reversion to a negative test. The frequency
      of indeterminate results of the IGRA was satisfying (3.5%). CONCLUSION: In case
      of only slightly elevated immune reactivity quantitative reporting of positive
      QFT-test results and a repeat test strategy might be of advantage for the
      usefulness of the test.

PMID- 23978525
TI  - Truncation of PstS1 antigen of Mycobacterium tuberculosis improves diagnostic
      efficiency.
AB  - PstS1, also named 38-kDa antigen, is one of the earliest known immune-dominant
      antigens of Mycobacterium tuberculosis and it has been commonly used in
      serodiagnostic tests. We constructed a truncated version, tnPstS1, by removing 96
      and 14 amino acid residues from the N- and C-terminals, respectively of the
      native PstS1. The native and the truncated 29.5 kDa proteins were expressed in
      insoluble forms in Escherichia coli to levels of 15% and 25% of the total cell
      proteins, respectively. Both the variant molecules reacted equally well with the
      antisera raised in rabbit against the native protein. PstS1 and tnPstS1 were
      evaluated through ELISA against plasma samples from 160 culture positive
      tuberculosis patients and 40 healthy controls. With tnPstS1 43% of the patient
      samples were detected positive for the antibody as compared to only 36% in the
      case of the native PstS1. Data for the secondary structures of the native and the
      truncated variants as obtained by circular dichroism agreed with the known 3-D
      structure of the native protein and the predicted structure of the truncated
      version, respectively. The results show that the truncated tnPstS1 is more
      efficient as compared to the native PstS1 for use as a serodiagnostic agent.

PMID- 23978527
TI  - Further evidence for bias in observational studies of influenza vaccine
      effectiveness: the 2009 influenza A(H1N1) pandemic.
AB  - Preinfluenza periods have been used to test for uncontrolled confounding in
      studies of influenza vaccine effectiveness, but some authors have claimed that
      confounding differs in preinfluenza and influenza periods. We tested this claim
      by comparing estimates of the vaccine-mortality association during the 2009/2010
      influenza year, when there was essentially no circulation of seasonal influenza
      in the United States, and 2007/2008, a typical influenza year. We pooled data on
      seniors (adults aged >=65 years) from 7 US managed care organizations that
      participated in the Vaccine Safety Datalink Project. We defined influenza
      vaccination, all-cause mortality, and potential confounders from administrative
      databases. We quantified the vaccine-mortality association using Cox regression.
      During 2007/2008, the adjusted hazard ratio was 0.44 prior to influenza season,
      0.62 during influenza season, and 0.71 after influenza season. A similar pattern
      was observed during 2009/2010, when any effect of seasonal influenza vaccine
      observed during all time periods must have resulted from confounding: 0.65 during
      the autumn, 0.80 during the winter, and 0.84 during the summer. In a year with
      minimal seasonal influenza, we found no evidence that confounding in autumn
      preinfluenza periods is qualitatively different from confounding in winter. This
      supports the use of preinfluenza periods as control time periods in studies of
      influenza vaccine effectiveness. 

PMID- 23978528
TI  - Years of life lost in the first wave of the 2009 influenza A(H1N1) pandemic in
      Hong Kong.
AB  - The impact of influenza pandemics might be overestimated; the published studies
      of years of life lost (YLL) have typically ignored the presence of underlying
      chronic conditions or health risk behaviors in most deaths. We used data on
      deaths involving laboratory-confirmed 2009 influenza A(H1N1) virus infection that
      occurred between April 2009 and May 2010 in Hong Kong, China, to adjust for these
      underlying risk factors. Life expectancy was corrected with hazard-based
      modifications to the life tables. The excess hazards posed by underlying risk
      factors were added to the "baseline" age-specific hazards in the local life
      tables to reflect the life expectancy associated with each underlying risk
      factor. Of 72 deceased persons with laboratory-confirmed 2009 influenza A(H1N1)
      virus infection, 56% had underlying risk factors. We estimated that the 2009
      pandemic was associated with 1,540 (95% confidence interval: 1,350, 1,630) YLL
      after adjustment for age and underlying risk factors. This figure is
      approximately 25% lower than the YLL estimate of 2,080 derived after adjustment
      for age but not for risk factors. Our analysis demonstrates the potential scale
      of bias in YLL estimation if underlying risk factors are ignored. The estimation
      of YLL with correction for underlying risk factors in addition to age could also
      provide a framework for similar calculations elsewhere. 

PMID- 23978529
TI  - Effects of kinesiotaping on foot posture in participants with pronated foot: a
      quasi-randomised, double-blind study.
AB  - OBJECTIVE: To investigate whether kinesiotaping improves excessive foot pronation
      compared with sham kinesiotaping. DESIGN: Quasi-randomised, double-blind study.
      SETTING: One primary care centre. PARTICIPANTS: One hundred and thirty
      participants were screened for inclusion. Sixty-eight participants with pronated
      feet [Foot Posture Index (FPI)>= 6] were enrolled, and the follow-up rate was
      100%. INTERVENTIONS: Participants were allocated into one of two groups: an
      experimental kinesiotaping group (KT1) and a sham taping group (KT2). Measures
      were collected by a blinded assessor at baseline, and 1 minute, 10 minutes, 60
      minutes and 24 hours after taping. MAIN OUTCOME MEASURES: The primary outcome was
      total FPI score, and the secondary outcome was rear-foot FPI score. RESULTS:
      There were no significant differences in total FPI score between kinesiotaping
      and sham taping at any time point. Similarly, there were no significant
      differences in rear-foot FPI score, apart from at 60-minute follow-up when the
      difference between groups was significant (P=0.04) but the effect size was very
      small (0.85 points on the rear-foot FPI score between -6 and +6). CONCLUSIONS:
      Kinesiotaping does not correct foot pronation compared with sham kinesiotaping in
      people with pronated feet.

PMID- 23978530
TI  - Deceased-donor split-liver transplantation in adult recipients: is the learning
      curve over?
AB  - BACKGROUND: Infants have the highest wait-list mortality of all liver
      transplantation candidates. Deceased-donor split-liver transplantation, a
      technique that provides both an adult and pediatric graft, might be the best way
      to decrease this disproportionate mortality. Yet concern for an increased risk to
      adult split recipients has discouraged its widespread adoption. We aimed to
      determine the current risk of graft failure in adult recipients after split-liver
      transplantation. STUDY DESIGN: United Network for Organ Sharing data from 62,190
      first-time adult recipients of deceased-donor liver transplants (1995-2010) were
      analyzed (889 split grafts). Bivariate risk factors (p < 0.2) were included in
      Cox proportional hazards models of the effect of transplant type on graft
      failure. RESULTS: Split-liver recipients had an overall hazard ratio of graft
      failure of 1.26 (p < 0.001) compared with whole-liver recipients. The split-liver
      hazard ratio was 1.45 (p < 0.001) in the pre-Model for End-Stage Liver Disease
      era (1995-2002) and 1.10 (p = 0.28) in the Model for End-Stage Liver Disease era
      (2002-2010). Interaction analyses suggested an increased risk of split-graft
      failure in status 1 recipients and those given an exception for hepatocellular
      carcinoma. Excluding higher-risk recipients, split and whole grafts had similar
      outcomes (hazard ratio = 0.94; p = 0.59). CONCLUSIONS: The risk of graft failure
      is now similar between split and whole-liver recipients in the vast majority of
      cases, which demonstrates that the expansion of split-liver allocation might be
      possible without increasing the overall risk of long-term graft failure in adult
      recipients. Additional prospective analysis should examine if selection bias
      might account for the possible increase in risk for recipients with
      hepatocellular carcinoma or designated status 1.

PMID- 23978531
TI  - Prehospital trauma life support training of ambulance caregivers and the outcomes
      of traffic-injury victims in Sweden.
AB  - BACKGROUND: There is limited evidence that the widely implemented Prehospital
      Trauma Life Support (PHTLS) educational program improves patient outcomes. The
      primary aim of this national study in Sweden was to investigate the association
      between regional implementation of PHTLS training and mortality after traffic
      injuries. STUDY DESIGN: We extracted information from the Swedish National
      Patient Registry and the Cause of Death Registry on victims of motor-vehicle
      traffic injuries in Sweden from 2001 to 2004 (N = 28,041). During this time
      period, PHTLS training was implemented at a varying pace in different regions. To
      control for other influences on patient outcomes related to regional and hospital
      level effects, such as variations in performance of trauma care systems, we used
      Bayesian hierarchical regression models to estimate odds ratios for prehospital
      mortality and 30-day mortality after hospital admission. We also controlled for
      the calendar year for each injury to account for period effects. We analyzed the
      time to death after hospital admission and time to return to work using Cox's
      proportional hazards frailty models. RESULTS: After multivariable adjustment, the
      odds ratio for prehospital mortality with PHTLS-trained prehospital staff was
      1.54 (95% credibility interval, 1.07-2.13). For 30-day mortality among those
      surviving to hospital admission, the odds ratio was 0.85 (95% credibility
      interval, 0.45-1.48). There was no association between PHTLS training and time to
      death (hazard ratio = 0.99; 95% CI, 0.85-1.14) or time to return to work (hazard
      ratio = 0.98; 95% CI, 0.92-1.05). CONCLUSIONS: In this observational study, the
      implementation of PHTLS training did not appear to be associated with reduced
      mortality or ability to return to work after motor-vehicle traffic injuries.

PMID- 23978532
TI  - Van Nes rotationplasty as a treatment method for Ewing's sarcoma in a 14-month
      old.
AB  - INTRODUCTION: In recent years, the rotationplasty procedure has become popular
      amongst tumour surgeons as an alternative to endoprosthetic replacement or
      amputation. There are very few documented cases of this technique in young
      patients with malignancy. PRESENTATION OF CASE: We describe an extremely rare
      case of Ewing's sarcoma in a 14-month-old boy that involved the entire length of
      the left femur. At initial presentation, pulmonary metastatic spread had occurred
      and there was no neurovascular involvement. Complete response to neo-adjuvant
      chemotherapy was achieved prior to performing the definitive surgical procedure.
      DISCUSSION: This case highlights the many reconstructive options and difficulties
      encountered in managing such extremely young patients with aggressive malignant
      disease. In this case, a complete femoral excision was necessary and various
      treatment options were explored. These included irradiation and re-implantation,
      endoprosthetic replacement and manufacturing a custom growing prosthesis. Taking
      future functional, psychological and social implications into consideration, we
      performed a total femoral excision and Van Nes rotationplasty of the tibia at our
      institute. Histological analysis of the tumour resection showed clear tumour
      margins and at 1 year clinical review, the patient demonstrates good functional
      outcome with no evidence of disease recurrence. CONCLUSION: Van Nes
      rotationplasty is a viable reconstructive option in young patients with sarcoma
      of the femur. We believe this to be the youngest reported case of rotationplasty
      in current literature.

PMID- 23978533
TI  - Successful perioperative management of a patient with idiopathic thrombocytopenic
      purpura undergoing emergent appendectomy: Report of a case.
AB  - INTRODUCTION: Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease
      characterized by a low platelet count and normal bone marrow. Patients with ITP
      undergoing surgery are thought to have increased risk for postoperative
      complications because of their thrombocytopenia. PRESENTATION OF CASE: we report
      the case of a 66-year-old woman with ITP who required an emergency operation for
      acute appendicitis associated with disseminated intravascular coagulation.
      Preoperative therapy consisted of platelet transfusions only, and intraoperative
      hemostasis was achieved. Postoperatively, high-dose intravenous immunoglobulin
      (IVIg) therapy led to an increased, stable, and adequate platelet count and good
      hemostasis. DISCUSSION: The outcome of this case suggests that IVIg therapy is
      not always required for preoperative management of patients with. CONCLUSION:
      IVIg therapy may be useful for postoperative management after emergency surgery.

PMID- 23978534
TI  - JAK/STAT signaling is required for hinge growth and patterning in the Drosophila
      wing disc.
AB  - JAK/STAT signaling is localized to the wing hinge, but its function there is not
      known. Here we show that the Drosophila STAT Stat92E is downstream of Homothorax
      and is required for hinge development by cell-autonomously regulating hinge
      specific factors. Within the hinge, Stat92E activity becomes restricted to gap
      domain cells that lack Nubbin and Teashirt. While gap domain cells lacking
      Stat92E have significantly reduced proliferation, increased JAK/STAT signaling
      there does not expand this domain. Thus, this pathway is necessary but not
      sufficient for gap domain growth. We show that reduced Wingless (Wg) signaling
      dominantly inhibits Stat92E activity in the hinge. However, ectopic JAK/STAT
      signaling does not perturb Wg expression in the hinge. We report negative
      interactions between Stat92E and the notum factor Araucan, resulting in
      restriction of JAK/STAT signaling from the notum. In addition, we find that the
      distal factor Nub represses the ligand unpaired as well as Stat92E activity.
      These data suggest that distal expansion of JAK/STAT signaling is deleterious to
      wing blade development. Indeed, mis-expression of Unpaired within the presumptive
      wing blade causes small, stunted adult wings. We conclude that JAK/STAT signaling
      is critical for hinge fate specification and growth of the gap domain and that
      its restriction to the hinge is required for proper wing development. 

PMID- 23978535
TI  - Cytoplasmic polyadenylation is a major mRNA regulator during oogenesis and egg
      activation in Drosophila.
AB  - The GLD-2 class of poly(A) polymerases regulate the timing of translation of
      stored transcripts by elongating the poly(A) tails of target mRNAs in the
      cytoplasm. WISPY is a GLD-2 enzyme that acts in the Drosophila female germline
      and is required for the completion of the egg-to-embryo transition. Though a
      handful of WISPY target mRNAs have been identified during both oogenesis and
      early embryogenesis, it was unknown whether WISP simply regulated a small pool of
      patterning or cell cycle genes, or whether, instead, cytoplasmic polyadenylation
      was widespread during this developmental transition. To identify the full range
      of WISPY targets, we carried out microarray analysis to look for maternal mRNAs
      whose poly(A) tails fail to elongate in the absence of WISP function. We examined
      the polyadenylated portion of the maternal transcriptome in both stage 14
      (mature) oocytes and in early embryos that had completed egg activation. Our
      analysis shows that the poly(A) tails of thousands of maternal mRNAs fail to
      elongate in wisp-deficient oocytes and embryos. Furthermore, we have identified
      specific classes of genes that are highly regulated in this manner at each stage.
      Our study shows that cytoplasmic polyadenylation is a major regulatory mechanism
      during oocyte maturation and egg activation.

PMID- 23978536
TI  - High level expression, efficient purification and bioactivity assay of
      recombinant human platelet-derived growth factor AA dimer (PDGF-AA) from
      methylotrophic yeast Pichia pastoris.
AB  - Platelet-derived growth factors (PDGFs) are important biochemical mediators
      regulating many physiological and pathophysiological processes, including
      promotion of the chemotactic recruitment and proliferation of cells involved in
      wound repair. Previously, homodimers of rhPDGF-AA protein were purified from
      Escherichia coli. However, eukaryotic proteins often contain posttranslational
      modifications, such as glycosylation, that are required for biological functions.
      In this study, an efficient method was established to purify a glycosylated
      rhPDGF-AA dimer from P. pastoris culture media by one step CM Sepharose ion
      exchange chromatography yielding about 20mg/L of over 95% highly purified rhPDGF
      AA. Mass spectrometry analysis of the purified rhPDGF-AA displayed a molecular
      weight (MW) of 27,825.513Da, composed of a subunit with MW of 15,042.945Da and a
      subunit with MW of 12,904.374Da. The size difference is accounted for by
      differential glycosylation of the monomers. Biological activity of the rhPDGF-AA
      was confirmed by its ability to induce NIH/3T3 cells proliferation. The
      experimental procedure we have developed facilitates production of an active
      glycosylated rhPDGF-AA in large amounts for further research and drug
      development. 

PMID- 23978537
TI  - Expression and immunolocalisation of the endocytic receptors megalin and cubilin
      in the human yolk sac and placenta across gestation.
AB  - Megalin and cubilin are multifunctional endocytic receptors associated with many
      transporting epithelia. They play an essential role in transport of nutrients
      through the visceral yolk sac of rodents during embryogenesis. Here, we
      immunolocalise them to the endodermal layer of the human yolk sac, and to the
      syncytiotrophoblast and cytotrophoblast cells of placental villi. In villi, the
      protein level of both receptors increased with gestation. The mRNA for megalin
      remained constant, while that encoding cubilin increased with gestation. These
      results suggest megalin and cubilin may be important in human maternal-fetal
      transfer, and that they increase across gestation to facilitate this function. 

PMID- 23978539
TI  - Male pseudogynaecomastia following massive weight loss: introducing the
      superolateral pedicle.

PMID- 23978538
TI  - RTP801 immunoreactivity in retinal ganglion cells and its down-regulation in
      cultured cells protect them from light and cobalt chloride.
AB  - RTP801, a stress-related protein, is activated by adverse environmental
      conditions and inhibits the activity of mammalian target of rapamycin (mTOR) in
      promoting oxidative stress-dependent cell death. RTP801 exists both in the
      mammalian retina and the lens of the eye. Here, we observed RTP801
      immunoreactivity in some retinal ganglion cells. Intravitreal injection of cobalt
      chloride (CoCl2) to mimick hypoxia influenced retinal GFAP (glial fibrillary
      acidic protein) and heme oxygenase-1 (HO-1) levels, but did not affect RTP801
      immunoreactivity or mRNA content relative to GAPDH. However, RTP801 mRNA was
      elevated when compared with Brn3a mRNA, suggesting that RTP801 is activated in
      stressed Brn3a retinal ganglion cells. In cultures of RGC-5 cells, RTP801
      immunoreactivity was located in the cytoplasm and partly present in the
      mitochondria. An insult of blue light or CoCl2 increased RTP801 expression, which
      was accompanied by cell death. However, in cultures where RTP801 mRNA was down
      regulated, the negative influence of blue light and CoCl2 was blunted. Rapamycin
      nullified the CoCl2-induced up-regulation of RTP801 and attenuated cell death.
      Moreover, rapamycin was non-toxic to RGC-5 cells, even at a high concentration
      (10MUM). The protective effect of rapamycin on RGC-5 cells caused by the
      inhibition of RTP801 suggests that rapamycin might attenuate retinal ganglion
      cell death in situ, as in glaucoma. 

PMID- 23978540
TI  - Who impels nephrology: women.

PMID- 23978542
TI  - Women: medicine, their kidneys, and nephrology.
AB  - As an act of compassion, the art of caring for the sick has always depended on
      women. As a practical tradition of healing skills, the "wise" and "old" women of
      antiquity were the original founders of what would ultimately become medicine.
      Throughout the subsequent millennia that it took for the gradual transformation
      of the healing skills from a craft to a profession, women continued to contribute
      to its progress and development. Unfortunately, recorded history has marginalized
      much of their fundamental contributions because most extant and investigated
      medical texts of the past were authored by men. As medicine began to embrace the
      basic sciences and became a university-based and regulated profession, rules
      excluding women from entry into the profession were made stricter and more
      rigorously enforced. It is only in the latter half of the 19th century that, in
      the footsteps of the growing feminine movement, women were admitted to medical
      schools, and in the 20th century that they began to contribute in earnest to the
      science of medicine. This article recounts this progress and highlights how it
      affected our knowledge of kidney disease in women and the enlarging role of women
      in the relatively new discipline of nephrology.

PMID- 23978543
TI  - Gender and the prevalence and progression of renal disease.
AB  - In most experimental models of CKD, male animals progress more rapidly than
      females. Modulation of the hormonal milieu can replicate the effects of gender on
      the course of kidney disease. These observations suggest that sex hormones per se
      may be important determinants of the greater susceptibility of males to
      progressive kidney injury. The predominance of data in humans suggests that the
      course of nondiabetic kidney disease is more aggressive in men than women. Male
      gender is arguably also a risk factor for progression of diabetic nephropathy.
      Sex hormones directly or indirectly affect many cellular processes by modulating
      the synthesis of various cytokines, growth factors, and vasoactive agents. In
      particular, estrogen acts in a receptor-dependent mechanism to regulate genes
      involved in extracellular matrix metabolism. Estrogen has profound effects on
      transforming growth factor-beta signal transduction and on the renin-angiotensin
      system. These effects may contribute to alterations in kidney hemodynamics and
      affect kidney disease progression. Selective estrogen receptor modulators, agents
      that mimic many of the beneficial effects of estrogen without reproducing
      estrogen's deleterious effects on reproductive tissue, ameliorate the course of
      kidney disease in animal models and in postmenopausal women. 

PMID- 23978544
TI  - Hypertension in women.
AB  - One in 4 adults has hypertension worldwide, which equates to approximately 1
      billion individuals. Hypertension is a leading cause of death, and lowering blood
      pressure prevents mortality and morbidity in women and men. Although men have
      higher blood pressures compared with women at all ages, older women have a
      slightly higher prevalence of hypertension, and hypertension is more often
      uncontrolled in women. Hypertension associated with pregnancy and polycystic
      ovary syndrome is unique to women. Exogenous hormone administration in the form
      of oral contraceptives, and rarely postmenopausal hormone replacement,
      contributes to the burden of hypertension in women. Renovascular hypertension due
      to fibromuscular dysplasia is more common in women. Hypertension treatment should
      focus on lowering blood pressure and treating additional cardiovascular risk
      factors, and there is no evidence to support gender-specific approaches to
      lowering blood pressure and modifying cardiovascular risk. 

PMID- 23978546
TI  - Women and ESRD: modalities, survival, unique considerations.
AB  - Women currently constitute 44.3% of prevalent patients on hemodialysis and 47% of
      those on peritoneal dialysis. Women on dialysis do not experience the survival
      benefit seen in those not on dialysis. This loss of a survival advantage is
      partially related to a lower cardiovascular survival benefit along with a higher
      noncardiovascular mortality rate compared with their male counterparts. Of
      particular concern is the markedly higher mortality rates seen in women less than
      45 years of age on dialysis. There are several female hormonal abnormalities in
      the female dialysis patient that can result in menstrual irregularities,
      anovulation, infertility, sexual dysfunction, early menopause, accelerated bone
      loss, and potentially increased risk of cardiovascular complications. Although
      fertility is impaired in dialysis, conception occurs in 1% to 7% of women of
      childbearing years on dialysis. Hence, all women with a potential for pregnancy
      should be counseled regarding the risks of pregnancy and contraceptive options.
      There are specific gynecologic considerations unique to peritoneal dialysis,
      including hemoperitoneum, decreased fertility, and uterine prolapse. Sexual
      dysfunction is commonly seen in the female dialysis population and is associated
      with depression and a lower quality of life; however, despite the high
      prevalence, it is generally not assessed nor is it treated. Depression is also
      common in the female dialysis population. Like sexual dysfunction, depression is
      underdiagnosed and undertreated in this population.

PMID- 23978545
TI  - Women, kidney disease, and pregnancy.
AB  - Several glomerular diseases may occur in women of childbearing age. Pregnancy in
      such patients should be planned when the disease has been in remission for a
      minimum of 6 months to minimize maternal and fetal complications.
      Immunosuppressive agents should be optimized before conception to include those
      that are safe for pregnancy. The complexity of medical management when caring for
      these patients calls for a multidisciplinary team approach consisting of a
      nephrologist, rheumatologist, obstetrician, and pharmacist. This review will
      address the physiological changes of pregnancy that may affect glomerular disease
      presentation, activity, and diagnosis; specific glomerular diseases primary and
      secondary to systemic diseases in the context of pregnancy; fetal and maternal
      complications and long-term effects; diagnosis and differential diagnosis; and
      treatment strategies that are considered relatively safe with respect to fetal
      intrauterine exposure. 

PMID- 23978547
TI  - Prevention of cardiovascular disease in women: highlights for the clinician of
      the 2011 American Heart Association Guidelines.
AB  - The 2011 Update to the American Heart Association Effectiveness-Based Guidelines
      for the Prevention of Cardiovascular Disease in Women is designed to assist women
      and health professionals in understanding the cardiovascular disease risk for
      women and undertaking the most effective preventive interventions. Although
      coronary heart disease remains the leading cause of mortality for women in the
      United States, cardiovascular mortality among U.S. women has decreased
      dramatically each year since 2000, with the decline in mortality being steeper
      for women than for men. Nonetheless, since 1984, more women than men continue to
      die annually from cardiovascular disease. Half of the decrement in cardiovascular
      mortality for women since 2000 reflects the improved management of their
      established cardiovascular disease; the other half is attributable to reductions
      in their major coronary risk factors, hence the importance of this prevention
      guideline. 

PMID- 23978548
TI  - Women and CKD-mineral and bone disorder.
AB  - Development of CKD-mineral and bone disorder (MBD) increases morbidity and
      mortality in men and women with CKD. The corresponding link among bone disease,
      fracture, and extraskeletal calcifications has been the subject of much focus. In
      the general population, the incidence of cardiovascular disease is higher in men
      than women, and this gender differences in degree of calcification and morbidity
      is maintained in kidney disease. Gender differences in phosphorus and fibroblast
      growth factor-23 (FGF-23) have been described. Increases in both have been linked
      with increasing likelihood of death in the CKD population as a whole; however,
      this link is not as well described when looking at women alone. The clinical
      significance of these differences, and the potential associated outcomes, are
      poorly understood. Traditional understanding of bone disease in women without
      kidney disease may not be fully applicable in women with CKD. Use of bone
      densitometry is limited in this population, and the traditional preventative
      interventions may not be fully transferrable to women with CKD. 

PMID- 23978550
TI  - Women and transplantation: fertility, sexuality, pregnancy, contraception.
AB  - Since 1958, thousands of women with kidney transplants have become pregnant.
      Although most pregnancies in kidney transplant recipients are successful, they
      are high-risk endeavors. This seems more a function of the associated issues and
      comorbidities that often affect individuals with kidney transplants (eg,
      hypertension) or immunosuppression side effects rather than the kidney transplant
      per se. Regardless of the underlying pathophysiology, these pregnancies are
      associated with a high rate of preeclampsia diagnoses, preterm deliveries,
      Cesarean sections, and small-for-gestational-age babies. Given these risks, it is
      critical to counsel and inform transplant recipients and prospective transplant
      recipients of childbearing age and their partners regarding many aspects of
      pregnancy, including the need for contraception to prevent pregnancy after
      transplant, immunosuppression concerns, and the potential effect of pregnancy on
      the outcome of the mother, baby, and kidney transplant. 

PMID- 23978549
TI  - Women and kidney transplantation.
AB  - Kidney transplant is the best kidney replacement treatment for end-stage kidney
      disease. The first step in moving toward kidney transplantation is referral to a
      transplant center for transplant evaluation. Education of dialysis staff and
      health-care providers may help increase referrals for evaluation. Patient
      education has been shown to enhance patient completion of the evaluation process.
      Patients have difficulty asking others to donate a kidney, but this process can
      be improved with home and community education. Living donors are more likely to
      be women than men, especially spousal donors. Deceased donors are more likely to
      be males younger than 35 years of age. There is a slight decrease in the rate of
      transplantation of women as compared with men, although not statistically
      significant. Pretransplant development of anti-human leukocyte antigen antibodies
      is more common amongst women and can be a barrier to successful transplantation
      and may prolong the waiting time for transplant. The long-term management of
      cardiovascular risk factors, osteoporosis, and age-appropriate cancer screening
      need to be addressed with posttransplant recipients. Women have an overall
      increased patient and graft survival as compared with men after transplant. 

PMID- 23978551
TI  - Urology patients in the nephrology practice.
AB  - Urologists and nephrologists provide care to many mutual patients. This review
      addresses the initial management of upper urinary tract issues commonly seen in
      nephrology practice. Patients with hematuria without clear benign causes should
      be referred to urologists for workup to rule out urologic malignancies.
      Asymptomatic microscopic hematuria after negative workup should be followed with
      annual urinalysis with repeat urologic evaluation if it persists after 5 years.
      Hydronephrosis is another commonly encountered diagnosis. Functional urinary
      obstruction should be excluded using a diuretic nuclear renography in the
      appropriate population. Asymptomatic, stable hydronephrosis can be observed, but
      those with acute, symptomatic obstruction, or patients with suspected obstruction
      with signs of infection, should seek urologic care for intervention.
      Hydronephrosis is common in pregnant women; symptomatic patients merit
      intervention similar to nonpregnant patients. The management of patients with an
      acute stone episode is similar to that for those with hydronephrosis. Patients
      with first stone episodes need evaluation for risk factors for stone formation,
      whereas patients with identified risk factors or recurrent stones need
      comprehensive metabolic workup. Patients with incidentally found kidney masses
      should be referred to urology for possible intervention when they have solid
      kidney masses or cystic masses that need further evaluation.

PMID- 23978552
TI  - Comparison between multi-echo T2* with and without fat saturation pulse for
      quantification of liver iron overload.
AB  - PURPOSE: To test a magnetic resonance image (MRI) technique that uses an
      additional pulse in multi-echo T2* sequence that works to suppress the fat
      signal, in subjects with liver iron overload and concomitant presence of fat in
      the liver, which have been revealed as a major drawback that compromises the
      correct iron quantification by MRI. MATERIALS AND METHODS: Fifty magnetic
      resonance images of the liver (1.5T scanner) of individuals with blood ferritin
      increases were retrospectively reviewed for the presence of steatosis, using the
      sequence in and out of phase, and iron overloading, using two sequences T2 *
      multi-echo: one standard and other with additional fat suppression pulse. T2 *
      values and their standard deviations were analyzed statistically. RESULTS: Our
      results showed that a significantly lower standard deviation of T2* values is
      obtained when the fat saturation pulse is applied in patients with steatosis. We
      found that modulation of fat signal on liver iron overload resulted in a
      different categorization of some patients. In one case, the patient was re
      classified within normal levels of liver iron. CONCLUSION: Our findings may
      contribute to a better measure of liver iron overload with relevant implications
      for patient treatment and care.

PMID- 23978553
TI  - TMT-HCC: a tool for text mining the biomedical literature for hepatocellular
      carcinoma (HCC) biomarkers identification.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related
      mortality worldwide. New insights into the pathogenesis of this lethal disease
      are urgently needed. Chromosomal copy number alterations (CNAs) can lead to
      activation of oncogenes and inactivation of tumor suppressors in human cancers.
      Thus, identification of cancer-specific CNAs will not only provide new insight
      into understanding the molecular basis of tumor genesis but also facilitate the
      identification of HCC biomarkers using CNA. This paper presents the TMT-HCC
      system; it is a tool for text mining the biomedical literature for hepatocellular
      carcinoma (HCC) biomarkers identification. TMT-HCC provides researchers with a
      powerful way to identify and discern molecular biomarkers of HCC to inform
      diagnosis, prognosis, and treatment driver genes with causal roles in
      carcinogenesis is to detect genomic regions that under frequent alterations in
      cancers (CNAs). TMT-HCC also extracts protein-protein interactions from the full
      text of the scientific papers. The results provided that the integration of
      genomic and transcriptional data offers powerful potential for identifying novel
      cancer genes in HCC pathogenesis. 

PMID- 23978554
TI  - Mechanistic insights into extracorporeal photochemotherapy: efficient induction
      of monocyte-to-dendritic cell maturation.
AB  - Extracorporeal photochemotherapy (ECP) is a widely used immunotherapy for
      cutaneous T cell lymphoma, as well as immunomodulation of graft-versus-host
      disease (GVHD) and transplanted organ rejection. ECP's mechanism encompasses
      large-scale physiologic platelet induction of dendritic cells (DCs). The normal
      bidirectional immunologic talents of DCs likely contribute heavily to ECP's
      capacity to immunize against tumor antigens, while also suppressing transplant
      immunopathology. Our understanding of how ECP physiologically induces monocyte-to
      DC maturation can enhance the treatment's potency, potentially broaden its use to
      other cancers and autoimmune disorders and tailor its application to individual
      patients' diseases. ECP's next decade is filled with promise. 

PMID- 23978555
TI  - The relationship of platelet yield, donor's characteristic and apheresis
      instruments in China.
AB  - Platelet yield was associated with donor's characteristic and property of
      apheresis instruments. Here, we have analyzed the relationship of platelet yield,
      physiologic parameters of donors for different apheresis instruments in China.
      Data were consecutively retrieved from plateletapheresis donors during March 1,
      2007 and March 1, 2012. Three different apheresis instruments MCS+, Amicus, Trima
      system were used for plateletapheresis and defined as group 1, 2 and 3
      respectively. Totally 77,091 Plateletapheresis donations were performed in this
      study. 17 donations were finally aborted because of vasovagal reaction with
      syncope. 5861, 37,036, 34,177 donations were performed in group 1, 2 and 3
      respectively. Hct and platelet values before donations were similar, but platelet
      yield and collection rate were showed significantly difference (p<0.05) among the
      three groups. The values of platelet and Hct in the males before donations were
      higher than those in the females, and the platelet yield and collection rate were
      showed significantly difference between the male group and female group (p<0.05).
      The overall reaction rate was 1.56%. Most donors were chosen the group 2 (51.6%)
      for next donation, followed by group 3 (33%) and group 1 (15.4%). We concluded
      that the platelet yield and collection rate in the male group were higher than
      those in the female group and the efficiency of plateletapheresis was associated
      with the kind of apheresis instruments and donor's characteristic. These data
      will help to work out suitable apheresis protocol based on the Chinese donor's
      characteristic.

PMID- 23978556
TI  - The role of heat shock proteins in Amyotrophic Lateral Sclerosis: The therapeutic
      potential of Arimoclomol.
AB  - Arimoclomol is a hydroxylamine derivative, a group of compounds which have unique
      properties as co-inducers of heat shock protein expression, but only under
      conditions of cellular stress. Arimoclomol has been found to be neuroprotective
      in a number of neurodegenerative disease models, including Amyotrophic Lateral
      Sclerosis (ALS), and in mutant Superoxide Dismutase 1 (SOD1) mice that model ALS,
      Arimoclomol rescues motor neurons, improves neuromuscular function and extends
      lifespan. The therapeutic potential of Arimoclomol is currently under
      investigation in a Phase II clinical trial for ALS patients with SOD1 mutations.
      In this review we summarize the evidence for the neuroprotective effects of
      enhanced heat shock protein expression by Arimoclomol and other inducers of the
      Heat Shock Response. ALS is a complex, multifactorial disease affecting a number
      of cell types and intracellular pathways. Cells and pathways affected by ALS
      pathology and which may be targeted by a heat shock protein-based therapy are
      also discussed in this review. For example, protein aggregation is a
      characteristic pathological feature of neurodegenerative diseases including ALS.
      Enhanced heat shock protein expression not only affects protein aggregation
      directly, but can also lead to more effective clearance of protein aggregates via
      the unfolded protein response, the proteasome-ubiquitin system or by autophagy.
      However, compounds such as Arimoclomol have effects beyond targeting protein mis
      handling and can also affect additional pathological mechanisms such as oxidative
      stress. Therefore, by targeting multiple pathological mechanisms, compounds such
      as Arimoclomol may be particularly effective in the development of a disease
      modifying therapy for ALS and other neurodegenerative disorders.

PMID- 23978557
TI  - Synoviocyte neotissues towards in vitro meniscal tissue engineering.
AB  - Meniscal injuries are a common cause of pain and osteoarthritis in dogs. We
      describe here the production of synoviocyte-derived autologous neotissues for
      potential application in meniscal tissue engineering, via two different culture
      techniques: contracted or tensioned synthesis of synoviocyte neotissues.
      Synoviocytes were obtained during routine stifle arthroscopy and cultured from 14
      dogs with naturally occurring osteoarthritis of the stifle. Neotissues were
      analyzed for meniscal-like matrix components and their gene expression,
      inflammatory gene expression, and cell viability. Tension improved cell
      viability, and, independent of cell viability, fibrochondrogenic activity by
      promoting expression of collagen type 1 and aggrecan genes and attenuating gene
      expression of IL-6. Through this mechanism tension increased collagen protein
      content and chondrogenic index of neotissues. Alpha smooth muscle actin was
      present in all neotissues and was responsible for grossly visible contractile
      behavior. Application of tension to synoviocytes may be a viable culture method
      towards in vitro meniscal tissue engineering. 

PMID- 23978558
TI  - A comparative assessment of waste incinerators in the UK.
AB  - The uptake in Europe of Energy from Waste (EfW) incinerator plants has increased
      rapidly in recent years. In the UK, 25 municipal waste incinerators with energy
      recovery are now in operation; however, their waste supply chains and business
      practices vary significantly. With over a hundred more plant developments being
      considered it is important to establish best business practices for ensuring
      efficient environmental and operational performance. By reviewing the 25 plants
      we identify four suitable case study plants to compare technologies (moving
      grate, fluidised bed and rotary kiln), plant economics and operations. Using data
      collected from annual reports and through interviews and site visits we provide
      recommendations for improving the supply chain for waste incinerators and
      highlight the current issues and challenges faced by the industry. We find that
      plants using moving grate have a high availability of 87-92%. However, compared
      to the fluidised bed and rotary kiln, quantities of bottom ash and emissions of
      hydrogen chloride and carbon monoxide are high. The uptake of integrated
      recycling practices, combined heat and power, and post incineration non-ferrous
      metal collections needs to be increased among EfW incinerators in the UK. We
      conclude that one of the major difficulties encountered by waste facilities is
      the appropriate selection of technology, capacity, site, waste suppliers and heat
      consumers. This study will be of particular value to EfW plant developers,
      government authorities and researchers working within the sector of waste
      management. 

PMID- 23978559
TI  - Genome-wide identification and analysis of the aldehyde dehydrogenase (ALDH) gene
      superfamily in apple (Malus * domestica Borkh.).
AB  - Aldehyde dehydrogenases (ALDHs) represent a protein superfamily encoding
      NAD(P)(+)-dependent enzymes that oxidize a wide range of endogenous and exogenous
      aliphatic and aromatic aldehydes. In plants, they are involved in many biological
      processes and play a role in the response to environmental stress. In this study,
      a total of 39 ALDH genes from ten families were identified in the apple (Malus *
      domestica Borkh.) genome. Synteny analysis of the apple ALDH (MdALDH) genes
      indicated that segmental and tandem duplications, as well as whole genome
      duplications, have likely contributed to the expansion and evolution of these
      gene families in apple. Moreover, synteny analysis between apple and Arabidopsis
      demonstrated that several MdALDH genes were found in the corresponding syntenic
      blocks of Arabidopsis, suggesting that these genes appeared before the divergence
      of lineages that led to apple and Arabidopsis. In addition, phylogenetic
      analysis, as well as comparisons of exon-intron and protein structures, provided
      further insight into both their evolutionary relationships and their putative
      functions. Tissue-specific expression analysis of the MdALDH genes demonstrated
      diverse spatiotemporal expression patterns, while their expression profiles under
      abiotic stress and various hormone treatments indicated that many MdALDH genes
      were responsive to high salinity and drought, as well as different plant
      hormones. This genome-wide identification, as well as characterization of
      evolutionary relationships and expression profiles, of the apple MdALDH genes
      will not only be useful for the further analysis of ALDH genes and their roles in
      stress response, but may also aid in the future improvement of apple stress
      tolerance.

PMID- 23978560
TI  - 'JBR' has been a long-term supporter of both the ESVS and the EJVES.

PMID- 23978561
TI  - Lower prevalence than expected when screening 70-year-old men for abdominal
      aortic aneurysm.
AB  - BACKGROUND: Screening 65-year-old men for abdominal aortic aneurysms (AAA) is a
      cost-effective method to reduce the mortality from ruptured AAA. However,
      contemporary results show a lower than expected prevalence of AAA, thus
      questioning the benefit of screening. Since the prevalence increases with age, a
      possible way to enhance the benefit of screening might be to screen older men.
      Our aim was to determine the contemporary screening-detected prevalence among 70
      year-old men. METHODS: A total of 5,623 unscreened 70-year-old men were invited
      to ultrasound screening. Uni- and multivariable analyses were used to assess the
      risk factors for AAA. RESULTS: The attendance rate was 84.0%. The prevalence of
      previously unknown AAAs was 2.3%. When adding the 64 men with an already known
      AAA to the screening-detected ones, the total prevalence in the population was at
      least 3.0%, and the previously discovered AAAs constituted 37.4% of the total
      prevalence. "Ex smoker" and "Current smoker" were the most important risk
      factors. CONCLUSIONS: When screening 70-year-old men for AAA, the prevalence was
      less than half that expected, despite a high attendance rate. Smoking was the
      strongest risk factor. Almost 40% of the men with AAAs were already known from
      other means than screening.

PMID- 23978563
TI  - Experimental treatments for cocaine toxicity: a difficult transition to the
      bedside.
AB  - Cocaine is a commonly abused illicit drug that causes significant morbidity and
      mortality. Although there is no true antidote to cocaine toxicity, current
      management strategies address the life-threatening systemic effects, namely
      hyperthermia, vasospasm, and severe hypertension. Clinicians rely on rapid
      cooling, benzodiazepines, and alpha-adrenergic antagonists for management, with
      years of proven benefit. Experimental agents have been developed to more
      effectively treat acute toxicity. Pharmacodynamic approaches include
      antipsychotics that are thought to interfere with cocaine's actions at several
      neurotransmitter receptors. However, these medications may worsen the
      consequences of cocaine toxicity as they can interfere with heat dissipation,
      cause arrhythmias, and lower the seizure threshold. Pharmacokinetic approaches
      use cocaine-metabolizing enzymes, such as butyrylcholinesterase (BChE), cocaine
      hydrolase (CocH), and bacterial cocaine esterase (CocE). Experimental models with
      these therapies improve survival, primarily when administered before cocaine,
      although newer evidence demonstrates beneficial effects shortly after cocaine
      toxicity has manifested. CocE, a foreign protein, can induce an immune response
      with antibody formation. When enzyme administration was combined with vaccination
      against the cocaine molecule, improvement in cocaine-induced locomotor activity
      was observed. Finally, lipid emulsion rescue has been described in human case
      reports as an effective treatment in patients with hemodynamic compromise because
      of cocaine, which correlates well with its documented benefit in toxicity due to
      other local anesthetics. A pharmaceutical developed from these concepts will need
      to be expedient in onset and effective with minimal adverse effects while at the
      same time being economical. 

PMID- 23978562
TI  - Effects of intrathecal SNC80, a delta receptor ligand, on nociceptive threshold
      and dorsal horn substance p release.
AB  - Delta-opioid receptors (DOR) are present in the superficial dorsal horn and are
      believed to regulate the release of small afferent transmitters as evidenced by
      the effects of spinally delivered delta-opioid preferring peptides. Here we
      examined the effects of intrathecal SNC80 [(+)-4-[alpha(R)-alpha-[(2S,5R)-4-allyl
      2,5-dimethyl-1-piperazinyl]-3-(methoxybenzyl)-N,N-diethylbenzamide], a selective
      nonpeptidic DOR agonist, in three preclinical pain models, acute thermal escape,
      intraplantar carrageenan-tactile allodynia, and intraplantar formalin flinches,
      and on the evoked release of substance P (SP) from small primary afferents. Rats
      with chronic intrathecal catheters received intrathecal vehicle or SNC80 (100 or
      200 MUg). Intrathecal SNC80 did not change acute thermal latencies or carrageenan
      induced thermal hyperalgesia. However, SNC80 attenuated carrageenan-induced
      tactile allodynia and significantly reduced both phase 1 and phase 2 formalin
      induced paw flinches, as assessed by an automatic flinch counting device. These
      effects were abolished by naltrindole (3 mg/kg i.p.), a selective DOR antagonist,
      but not CTOP (10 ug i.t.), a selective MOR antagonist. Furthermore, intrathecal
      SNC80 (200 MUg) blocked formalin-induced substance P release otherwise evoked in
      the ispilateral superficial dorsal horn as measured by NK1 receptor
      internalization. In conclusion, intrathecal SNC80 alleviated pain
      hypersensitivity after peripheral inflammation in a fashion paralleling its
      ability to block peptide transmitter release from small peptidergic afferents,
      which by its pharmacology appears to represent an effect mediated by a spinal
      DOR. 

PMID- 23978564
TI  - Recombinant goose-type lysozyme in channel catfish: lysozyme activity and
      efficacy as plasmid DNA immunostimulant against Aeromonas hydrophila infection.
AB  - The objectives of this study were: 1) to investigate whether recombinant channel
      catfish lysozyme-g (CC-Lys-g) produced in Escherichia coli expression system
      possesses any lysozyme activity; and 2) to evaluate whether channel catfish
      lysozyme-g plasmid DNA could be used as an immunostimulant to protect channel
      catfish against Aeromonas hydrophila infection. Recombinant CC-Lys-g produced in
      E. coli expression system exhibited significant (P < 0.05) lytic activity against
      Gram-positive Micrococcus lysodeikticus and Gram-negative A. hydrophila. When
      pcDNA3.2-vectored recombinant channel catfish lysozyme-g (pcDNA-Lys-g) was
      transfected in channel catfish gill cells G1B, the over-expression of pcDNA-Lys-g
      offered significant (P < 0.05) protection to G1B cells against A. hydrophila
      infection. When channel catfish were intraperitoneally injected with pcDNA-Lys-g
      along with an adjuvant QCDCR, the transcriptional level of Lys-g was
      significantly (P < 0.05) increased. When pcDNA-Lys-g injected fish was challenged
      with a highly virulent A. hydrophila strain AL-09-71, pcDNA-Lys-g offered 100%
      protection to channel catfish at two days post DNA injection. Macrophages of fish
      injected with pcDNA-Lys-g produced significantly (P < 0.05) higher amounts of
      reactive oxygen species and nitric oxide than that of fish injected with pcDNA
      vector alone at two days post DNA injection. Taken together, our results suggest
      that pcDNA-Lys-g could be used as a novel immunostimulant to offer immediate
      protection to channel catfish against A. hydrophila infection. 

PMID- 23978565
TI  - A teleostean counterpart of ferritin M subunit from rock bream (Oplegnathus
      fasciatus): an active constituent in iron chelation and DNA protection against
      oxidative damage, with a modulated expression upon pathogen stress.
AB  - Ferritins are biological iron chelators that can sequestrate excess iron to
      maintain iron homeostasis in the body. Ferritins basically consist of 2 types of
      subunits, designated as H and L. However, another new subunit, ferritin "M" which
      possesses characteristic features of both the H and L subunits, was recently
      identified in lower vertebrates, mostly in fish. In this study, a ferritin M-like
      subunit from rock bream (Oplegnathus fasciatus) (RbFerM) was characterized at the
      molecular level, and its transcriptional profile was analyzed in healthy fish, as
      well as in pathogen- and mitogen-stimulated fish. Furthermore, its functional
      properties were evaluated using the recombinant protein. The complete coding
      sequence of RbFerM was 528 bp in length, encoding a 176-amino acid peptide with a
      calculated molecular mass of 20 kDa. In silico analysis of RbFerM revealed that
      it has features similar to both the mammalian ferritin subunits, H and L.
      Phylogenetic analysis depicted the higher evolutionary proximity of RbFerM with
      its fish counterparts. Quantitative real time polymerase chain reaction (PCR)
      analysis detected a ubiquitous transcriptional profile of RbFerM in selected
      tissues of rock bream, in which more pronounced expression was observed in blood
      and liver tissues. Significant transcriptional inductions of RbFerM were detected
      in liver tissues upon lipopolysaccharides (LPS), Edwardsiella tarda,
      Streptococcus iniae, and rock bream irido virus (RBIV) exposures in time-course
      immune-challenge experiments. The purified recombinant protein of RbFerM
      demonstrated detectable iron chelating activity that varied with the temperature.
      Moreover, the recombinant RbFerM rendered a detectable protection effect against
      iron (II) and H2O2-mediated DNA damage.

PMID- 23978566
TI  - Characterization of two negative regulators of the Toll-like receptor pathway in
      Apostichopus japonicus: inhibitor of NF-kappaB and Toll-interacting protein.
AB  - The Toll-like receptor (TLR) signaling cascade plays a central role in host cell
      recognition and responses to microbial pathogens via the specific recognition of
      distinct pathogen-associated molecular patterns (PAMPs). However, no negative
      regulators of the TLR-signaling cascade have been described in sea cucumber
      (Apostichopus japonicus). In the present study, two negative regulators known as
      the inhibitor of NF-kappaB (IkappaB) and Toll-interacting protein (Tollip) have
      been identified in coelomocytes of this species using transcriptome sequencing
      and RACE (denoted as AjIkappaB and AjTollip, respectively). Both of these factors
      share a remarkably high degree of structural conservation with their mammalian
      orthologs, such as a central ankyrin repeat domain (ARD) for the deduced amino
      acids of AjIkappaB and the C2 and CUE domains for AjTollip. Constitutive
      expression patterns with differential expression levels were observed for these
      two genes. Moreover, mRNA transcript expression for AjIkappaB and AjTollip was
      highest in the tentacle and abundant in the muscle, respectively. Vibrio
      splendidus challenge study revealed that the expression level of these two genes
      was decreased within the first 48 h with 0.53-fold and 0.61-fold decrease
      compared with that in the control group for AjIkappaB and AjTollip, respectively.
      Taken together, these results indicated that AjIkappaB and AjTollip functioned as
      negative regulators in the TLR cascade in response to a V. splendidus challenge.

PMID- 23978567
TI  - Is there room for punctuated equilibrium in macroevolution?
AB  - The long-controversial theory of punctuated equilibrium (PE) asserts that
      speciation causes rapid evolution against a backdrop of stasis. PE is currently
      undergoing a resurgence driven by new developments in statistical methods.
      However, we argue that PE is actually a tangle of four unnecessarily conflated
      questions: (i) is evolution gradualistic or pulsed? (ii) does trait evolution
      occur mainly at speciation or within a lineage? (iii) are changes at speciation
      adaptive or neutral? and (iv) how important is species selection in shaping
      patterns of diversity? We discuss progress towards answering these four questions
      but argue that combining these conceptually distinct ideas under the single
      framework of PE is distracting and confusing, and more likely to hinder progress
      than to spur it. 

PMID- 23978568
TI  - tCFA15, a trimethyl cyclohexenonic long-chain fatty alcohol, affects neural stem
      fate and differentiation by modulating Notch1 activity.
AB  - We have investigated the effects of tCFA15, a non-peptidic compound, on the
      differentiation of neural stem cell-derived neurospheres, and have found that
      tCFA15 promotes their differentiation into neurons and reduces their
      differentiation into astrocytes, in a dose-dependent manner. This response is
      reminiscent of that resulting from the loss-of-function of Notch signaling after
      inactivation of the Delta-like 1 (Dll1) gene. Further analysis of the expression
      of genes from the Notch pathway by reverse transcriptase-PCR revealed that tCFA15
      treatment results in a consistent decrease in the level of Notch1 mRNA. We have
      confirmed this result in other cell lines and propose that it reflects a general
      effect of the tCFA15 molecule. We discuss the implications of this finding with
      respect to regulation of Notch activity in neural stem cells, and the possible
      use of tCFA15 as a therapeutic tool for various pathologies that result from
      impairment of Notch signaling. 

PMID- 23978569
TI  - Differential inhibition of signaling pathways by two new imidazo-pyrazoles
      molecules in fMLF-OMe- and IL8-stimulated human neutrophil.
AB  - N-formyl-methionyl-leucyl-phenylalanine (fMLF), its methyl ester fMLF-OMe and
      interleukin 8 (IL8) play a pivotal role in neutrophil chemotaxis regulation in
      the latter and early stages, respectively, but the mechanisms through which the
      signal transduction pathways activate this function are not yet completely
      understood. Compounds 3l and 3r, a new class of arylcarbamoyl-imidazo-pyrazoles
      derivatives, were described as the first example of compounds able to inhibit
      human neutrophil chemotaxis induced by both fMLF-OMe and IL8. Here, we report
      their effects on superoxide production and lysozyme release. No inhibition was
      observed, thus they could be defined as "pure" chemotactic antagonists.
      Therefore, such molecules were used to highlight specific kinases involved in
      neutrophil chemotaxis. Our data provide support that compounds 3l and 3r strongly
      inhibit p38 MAPK with either fMLF-OMe or IL8 chemoattractants, while they show
      different signaling pathways regarding PKC isoforms suggesting that a fine tuning
      of the neutrophil activation occurs through differences in the activation of
      signaling pathways. Neither fMLF-OMe nor IL8 were able to obtain activation of
      the PI3K/Akt pathway. Since anomalous activation of neutrophil recruitment is one
      of the causes of many inflammatory diseases, the good versatility of our
      derivatives could represent the most important characteristic of these new
      molecules in the development of novel therapeutics. 

PMID- 23978570
TI  - Association of interleukin-18 gene polymorphisms with the outcomes of hepatitis C
      virus infection in high-risk Chinese Han population.
AB  - Interleukin 18 (IL-18) gene polymorphisms have been reported to be associated
      with the outcomes of hepatitis C virus (HCV) infection in Americans, Indians and
      Europeans. We aimed to investigate whether the association can be replicated in
      Chinese Han population. Three IL-18 variants, -656G>T, -137G>C and +105A>C, were
      genotyped in three independent Han cohorts consisting of 552 cases and 784
      controls. By using logistic regression analysis and multiple testing, haplotype
      GCC were associated with a protection from susceptibility to HCV. After
      stratified analysis, both the carriage of -137C allele in the older or
      hemodialysis subgroup and the carriage of +105C allele in the younger subgroup
      were found to be significantly associated with a decreased risk of HCV
      susceptibility. By using logistic regression analysis and multiple testing for
      the resolution of HCV infection, our study showed that +105C allele and haplotype
      GGC displayed a negative effect on HCV persistence. After stratified analysis, a
      significantly decreased risk for HCV persistence was found in +105C allele in the
      subgroups of young, male or female, drug user or hemodialysis and HCV-1 or HCV
      mixed genotype. No significant association was observed between -656G>T and the
      outcomes of HCV infection. Our results demonstrated that the carriage of -137C
      allele, +105C allele, haplotype -656G/-137C/+105C and haplotype -656G/-137G/+105C
      of IL-18 gene may contribute to better outcomes of HCV infection in high-risk
      Chinese Han population. 

PMID- 23978571
TI  - Ambulatory percutaneous endovascular abdominal aortic aneurysm repair.
AB  - OBJECTIVE: Percutaneous endovascular abdominal aortic aneurysm repair (PEVAR) has
      been associated with fewer groin wound complications and shorter operative times,
      but same-day discharge (SDD) has not been reported. The goal of our article is to
      assess the feasibility and safety of ambulatory PEVAR and identify patient
      characteristics that are eligible for this approach. METHODS: Consecutive
      patients who underwent elective endovascular abdominal aortic aneurysm repair
      (EVAR) between March 2011 and December 2012 were reviewed. SDD was discussed
      during the preoperative visit with patients who were functionally independent,
      without significant comorbidities, and had favorable anatomy. These patients were
      given the option to be discharged in the evening of the PEVAR after 6 hours of
      bed rest if the procedure was uneventful. Causes for discharge delay and early
      outcomes were analyzed. RESULTS: During the study period, 79 patients underwent
      abdominal aortic aneurysm (AAA) repair, 64 of whom (mean age, 70.2 +/- 9.9;
      range, 59-97) had elective EVAR (3 ruptures, 5 acute presentations, 3 fenestrated
      EVARs, 4 elective open AAA repairs were excluded). Fifty-three patients (83%) had
      bilateral percutaneous access, seven had unilateral percutaneous (11%) access,
      and the remaining four (6%) had bilateral femoral endarterectomies. The
      percutaneous closure success rate was 96% in 113 attempts (three conversions for
      inadequate hemostasis, one for inability to deploy device). Mean length of stay
      was 1.3 +/- 1.4 days (median, 1 day) with no 30-day mortality. Twenty-one
      patients (33%) were discharged the same day (SDD group), 24 (37%) on
      postoperative day (POD) 1, 16 (25%) on POD 2/3, and 3 (5%) stayed >= 4 days. One
      patient in the SDD group was readmitted on POD 3 after EVAR for severe
      postimplantation syndrome. Of the 23 patients who were discharged on POD 1, 10
      were kept overnight due to severe chronic obstructive pulmonary disease, coronary
      artery disease, or advanced age, three transportation issues, two inability to
      void, two patient preference, two for renal protection, and four due to unplanned
      femoral cutdown. Patients in the SDD group were significantly younger (66.5 +/-
      5.4 years vs 72.0 +/- 10.6 years; P = .029), had smaller AAAs (5.3 +/- 0.5 cm vs
      5.9 +/- 1.0 cm; P = .013), less blood loss (115 +/- 90 mL vs 232 +/- 198 mL; P =
      .012), and shorter operating time (79 +/- 24 minutes vs 121 +/- 73 minutes; P =
      .013). There were fewer American Society of Anesthesiologists 4 patients in the
      SDD group (24% vs 48%; P = .056). The majority (81%) of patients in all groups
      had general anesthesia (86% vs 79% SDD vs others; P = .523). CONCLUSIONS:
      Ambulatory PEVAR was found to be feasible and safe in one-third of patients
      undergoing elective EVAR who did not have excessive medical risk, had good
      functional capacity, and underwent an uneventful procedure. The impact of SDD on
      cost-effectiveness needs to be further assessed and may not be feasible in
      hospitals reimbursed based on admission status.

PMID- 23978572
TI  - One-year outcomes from an international study of the Ovation Abdominal Stent
      Graft System for endovascular aneurysm repair.
AB  - OBJECTIVE: This study evaluated 1-year safety and effectiveness outcomes of the
      United States regulatory trial for the Ovation Abdominal Stent Graft System
      (TriVascular Inc, Santa Rosa, Calif) for endovascular repair of abdominal aortic
      aneurysms (AAAs). METHODS: This prospective, multicenter, single-arm trial was
      conducted at 36 sites in the United States, Germany, and Chile to evaluate the
      safety and effectiveness of the Ovation stent graft. From November 2009 to May
      2011, 161 patients (88% males; mean age, 73 +/- 8 years) with AAAs (mean
      diameter, 54 +/- 9 mm) were treated with the Ovation stent graft. The main body
      is a modular two-docking limb device with a 14F outer diameter delivery system,
      active suprarenal fixation, and polymer-filled proximal rings that accommodate
      the aortic neck for seal. Main inclusion criteria included proximal aortic neck
      length >= 7 mm, inner neck diameter between 16 and 30 mm, distal iliac landing
      zones length >= 10 mm, and diameter between 8 and 20 mm. Patients were treated
      under a common protocol, including clinical and imaging follow-up at discharge,
      30 days, 6 months, and annually through 5 years. A Clinical Events Committee
      adjudicated adverse events, an independent imaging core laboratory analyzed
      imaging, and a Data Safety and Monitoring Board provided study oversight.
      Complete 1-year follow-up data were available for this report. RESULTS: The
      Ovation stent graft was implanted successfully in 161 patients (100%), including
      69 (42.9%) by percutaneous access. General anesthesia was used in 106 patients
      (65.8%). Technical success was 100%, and mean procedure time was 110 minutes.
      Median procedural blood loss was 150 mL, and median hospital stay was 1 day. The
      30-day major adverse event rate was 2.5%. At 1 year, AAA-related and all-cause
      mortality were 0.6% and 2.5%, respectively. Major adverse event and serious
      adverse event rates through 1 year were 6.2% and 38.5%, respectively. The 1-year
      treatment success rate was 99.3%. The imaging core laboratory reported no stent
      graft migration or type I, III, or IV endoleaks. At 1 year, type II endoleaks
      were identified in 34% of patients, and AAA enlargement was identified in one
      patient (0.7%). No AAA rupture or conversion to open surgery was reported. AAA
      related secondary procedures were performed in 10 patients (6.2%) for 12
      findings, including endoleak (six), aortic main body stenosis (three), and iliac
      limb stenosis or occlusion (three). CONCLUSIONS: The 1-year results of the
      Ovation Abdominal Stent Graft System demonstrate excellent safety and
      effectiveness in treatment of patients with AAAs, particularly in patients with
      challenging anatomic characteristics, including short aortic necks and narrow
      iliac arteries. Longer-term follow-up is needed.

PMID- 23978573
TI  - Operative and nonoperative management of chronic disseminated intravascular
      coagulation due to persistent aortic endoleak.
AB  - Disseminated intravascular coagulation (DIC) due to endoleak is a rare
      complication following endovascular aneurysm repair. Two of the four previously
      reported cases occurred in patients with cirrhosis. We describe three patients
      with normal liver function who developed DIC due to delayed high-flow (type Ia or
      III) endoleaks. Two patients underwent successful surgical repair, and the third
      was managed medically. All three patients had chronic thrombocytopenia prior to
      developing an endoleak as did the four reported cases in the literature. We
      propose that thrombocytopenia, like cirrhosis, be considered a risk factor for
      DIC due to endoleaks in patients undergoing endovascular aneurysm repair. 

PMID- 23978574
TI  - Childhood maltreatment and post-traumatic stress disorder among incarcerated
      young offenders.
AB  - Young offenders have a high prevalence of mental illness and a large proportion
      report experiencing a number of traumatic events during childhood, but there is
      little research exploring this association. This study describes the prevalence
      of, and association between, child maltreatment and post-traumatic stress
      disorder (PTSD) among young offenders. The study uses data collected as part of
      the 2009 NSW Young People in Custody Health Survey which was conducted in nine
      juvenile detention centers. This paper reports on findings from the baseline
      questionnaires and 18-months of re-offending data. The analysis included 291
      participants who were assessed for PTSD and child maltreatment. The sample was
      88% male, 48% Aboriginal, with an average age of 17 years (range 13-21 years).
      One in five (20%) participants were diagnosed with PTSD, with females
      significantly more likely to have PTSD than males (40% vs. 17%, p<0.05). Over
      half (60%) of young offenders reported any child abuse or neglect, with females
      nearly 10 times more likely to report three or more kinds of severe child
      maltreatment than males. The main correlate for a diagnosis of PTSD was having
      three or more kinds of severe child maltreatment (OR=6.73, 95% CI: 1.06-42.92).
      This study provides evidence for the need to comprehensively assess child abuse
      and neglect among young offenders in order to provide appropriate treatment in
      custody and post-release. 

PMID- 23978575
TI  - Impacts of adverse childhood experiences on health, mental health, and substance
      use in early adulthood: a cohort study of an urban, minority sample in the U.S.
AB  - Research has shown that adverse childhood experiences (ACEs) increase the risk of
      poor health-related outcomes in later life. Less is known about the consequences
      of ACEs in early adulthood or among diverse samples. Therefore, we investigated
      the impacts of differential exposure to ACEs on an urban, minority sample of
      young adults. Health, mental health, and substance use outcomes were examined
      alone and in aggregate. Potential moderating effects of sex were also explored.
      Data were derived from the Chicago Longitudinal Study, a panel investigation of
      individuals who were born in 1979 or 1980. Main-effect analyses were conducted
      with multivariate logistic and OLS regression. Sex differences were explored with
      stratified analysis, followed by tests of interaction effects with the full
      sample. Results confirmed that there was a robust association between ACEs and
      poor outcomes in early adulthood. Greater levels of adversity were associated
      with poorer self-rated health and life satisfaction, as well as more frequent
      depressive symptoms, anxiety, tobacco use, alcohol use, and marijuana use.
      Cumulative adversity also was associated with cumulative effects across domains.
      For instance, compared to individuals without an ACE, individuals exposed to
      multiple ACEs were more likely to have three or more poor outcomes (OR range=2.75
      10.15) and four or more poor outcomes (OR range=3.93-15.18). No significant
      differences between males and females were detected. Given that the consequences
      of ACEs in early adulthood may lead to later morbidity and mortality, increased
      investment in programs and policies that prevent ACEs and ameliorate their
      impacts is warranted. 

PMID- 23978577
TI  - Emergency department boarding times for patients admitted to intensive care unit:
      Patient and organizational influences.
AB  - INTRODUCTION: Critically ill patients can be subject to prolonged stays in the
      emergency department following receipt of an order to admit to an intensive care
      unit. The purpose of this study was to explore patient and organizational
      influences on the duration of boarding times for intensive care bound patients.
      METHODS: This exploratory descriptive study was situated in a Canadian hospital
      in northern Ontario. Through a six-month retrospective review of three data
      sources, information was collected pertaining to 16 patient and organizational
      variables detailing the emergency department boarding time of adults awaiting
      transfer to the intensive care unit. Data analysis involved descriptive and non
      parametric methods. RESULTS: The majority of the 122 critically ill patients
      boarded in the ED were male, 55 years of age or older, arriving by ground
      ambulance on a weekday, and had an admitting diagnosis of trauma. The median
      boarding time was 34 min, with a range of 0-1549 min. Patients designated as most
      acute, intubated, and undergoing multiple diagnostic procedures had statistically
      significantly shorter boarding times. DISCUSSION: The study results provide a
      profile that may assist clinicians in understanding the complex and site-specific
      interplay of variables contributing to boarding of critically ill patients.

PMID- 23978576
TI  - Perspectives on trauma-informed care from mothers with a history of childhood
      maltreatment: a qualitative study.
AB  - Women who experienced abuse or neglect as children are more likely to have health
      problems during pregnancy and postpartum, but can be reluctant to seek help due
      to a lack of trauma-informed services. As part of a larger mixed method study,
      this component aimed to obtain qualitative data from trauma-exposed new mothers
      about their health care preferences during the perinatal period with the ultimate
      goal to design personalized, supportive interventions. Fifty-two trauma-exposed
      mothers completed a semi-structured interview at seven months postpartum about
      health care preferences including ideas for programs that promote wellness,
      thoughts about the influences of being a new mother and possible names for a
      program serving trauma-exposed mothers. Interviews were transcribed and coded
      using N-Vivo. Participants described ambivalence about seeking help but also a
      sincere desire for healing, coupled with hope for the future. This tension was
      apparent in the discussions highlighting the importance of access to experienced,
      nonjudgmental, and knowledgeable health and social care staff and volunteers, the
      wish for both formal, integrated physical and mental health services, and for
      informal opportunities to meet other trauma-exposed mothers in a non
      stigmatizing, child-friendly setting. Finally, positive relationship-building,
      respect, and safety were identified as key elements of services critical to
      counteract trauma-related shame and mistrust in others. Services for trauma
      exposed mothers should acknowledge the normal ambivalence surrounding seeking
      help, but promote hope-affirming practices in a family-centered, safe, non
      clinical setting that involves children, builds social support, and provides peer
      interaction. Program names should reflect optimism and healing rather than
      trauma. 

PMID- 23978578
TI  - Diastereomers of lithospermic acid and lithospermic acid B from Monarda fistulosa
      and Lithospermum erythrorhizon.
AB  - Monardic acids A (1) and B (2), which are (7R,8R) diastereomers of lithospermic
      acid (LA) and lithospermic acid B, respectively, were isolated from Monarda
      fistulosa. A (7S,8R) isomer (3) of LA was also isolated from this plant, and a
      (7R,8S) isomer (7) of LA was obtained from Lithospermum erythrorhizon. The
      absolute configuration of 1 was confirmed by analysis of its hydrolysates, 7
      epiblechnic acid and 2R-3-(3,4-dihydroxyphenyl)-2-hydroxypropanoic acid. The
      configuration in the dihydrobenzofuran moieties of 2, 3, and 7 was extrapolated
      by using the phenylglycine methyl ester method and a Cotton effect at
      approximately 250-260 nm in their electronic circular dichroism spectra.
      Diastereomers (1-3 and 7) displayed moderate hyaluronidase inhibitory and
      histamine release inhibitory activities.

PMID- 23978579
TI  - Racemosins A and B, two novel bisindole alkaloids from the green alga Caulerpa
      racemosa.
AB  - Racemosin A (1), a structurally unique bisindole alkaloid possessing the seco
      indolo[3,2-a]carbazole skeleton with two uncommon indolinenone units both
      conjugated with a methyl propenoate moiety, and its unusual cyclized derivative,
      racemosin B (2), were isolated from the green alga Caulerpa racemosa, together
      with the most commonly encountered pigment in the genus Caulerpa, caulerpin (3).
      Their structures were elucidated by extensive spectroscopic analysis and by
      comparison with data for related known compounds. A plausible biosynthetic
      pathway of 1 and 2 was proposed. In a neuro-protective assay, compound 1
      significantly attenuated the Abeta2(5-35)-induced SH-SY5Y cell damage with a
      14.6% increase in cell viability at the concentration of 10MUM when compared to
      epigallocatechin gallate (EGCG, 16.57% increase at 10 MUM) as the positive
      control.

PMID- 23978580
TI  - 8-9' linked neolignans with cytotoxicity from Alpinia conchigera.
AB  - Five new 8-9' linked neolignans conchigeranals A-E (1-5), together with three
      known compounds galanganal (6), galanganols A (7) and B (8), were isolated from
      the whole plant of Alpinia conchigera. Their structures were established by
      spectroscopic analysis, including 2D-NMR spectroscopic techniques. Cytotoxicities
      of compounds 1-8 were tested against two cancer cell lines A549 and Hela. Results
      showed that 4, 5, 7 and 8 exhibited cytotoxicity against A549 with the IC50
      values of 12.36, 9.72, 10.26, 13.05 MUg/ml, respectively, and 1-8 against Hela
      with the IC50 values from 1.53 to 5.29 MUg/ml.

PMID- 23978581
TI  - Inactivation of jack bean urease by scutellarin: elucidation of inhibitory
      efficacy, kinetics and mechanism.
AB  - In the present study, the inactivation effect of scutellarin (SL) on jack bean
      urease was investigated to elucidate the inhibitory potency, kinetics and
      mechanism of inhibition. It was revealed that SL acted as a concentration- and
      time-dependent inactivator of urease characteristic of slow-binding inhibition
      with an IC50 of 1.35+/-0.15 mM. The rapid formation of the initial SL-urease
      complex with an inhibition constant of Ki=5.37*10(-2) mM was followed by a slow
      isomerization into the final complex with the overall inhibition constant of
      Ki*=3.49*10(-3) mM. High effectiveness of thiol protectors, such as L-cysteine (L
      cys), 2-mercaptoethanol (2-ME) and dithiothreitol (DTT) significantly slowed down
      the rate of inactivation, indicating the strategic role of the active site
      sulfhydryl group in the blocking process. While the insignificant protection by
      boric acid and fluoride from the inactivation further confirmed that the active
      site cysteine should be obligatory for urease inhibition, which was also
      rationalized by the molecular docking study. The inhibition of SL on urease
      proved to be reversible since SL-blocked urease could be reactivated by DTT
      application and multidilution. The results obtained indicated that urease
      inactivation resulted from the reaction between SL and the sulfhydryl group.

PMID- 23978582
TI  - Effects of paeoniflorin on tumor necrosis factor-alpha-induced insulin resistance
      and changes of adipokines in 3T3-L1 adipocytes.
AB  - TNFalpha plays an important role in the adipocyte dysfunction, including
      lipolysis acceleration, insulin resistance and changes of adipokines. Recently,
      we showed that paeoniflorin attenuates adipocyte lipolysis and inhibits the
      phosphorylation of ERK, JNK, IKK stimulated by TNFalpha. However, the effects of
      paeoniflorin on adipocytes insulin resistance and changes of adipokines remain
      unknown. The aim of the current study was to investigate the role of paeoniflorin
      in preventing insulin resistance or inflammation in 3T3-L1 adipocytes treated
      with TNFalpha. Our results showed that paeoniflorin restored insulin-stimulated
      [(3)H]2-DOG uptake, which was reduced by TNFalpha, with concomitant restoration
      in serine phosphorylation of IRS-1 and insulin-stimulated phosphorylation of AKT
      in adipocytes. Paeoniflorin attenuated TNFalpha-mediated suppression of the
      expressions of PPARgamma and PPARgamma target genes, and the improvement of
      paeoniflorin on TNFalpha-induced insulin resistance was attenuated by GW9662, an
      antagonist of PPARgamma activity. Moreover, paeoniflorin could inhibit the
      expressions and secretions of IL-6 and MCP-1 from adipocytes induced by TNFalpha.
      These results, together with our previous data, indicate that paeoniflorin exerts
      a beneficial effect on adipocytes to prevent TNFalpha-induced insulin resistance
      and inflammatory adipokine release. Our studies provide important evidence for an
      ability of paeoniflorin in amelioration of TNFalpha-induced adipocyte
      dysfunction, which would be helpful to clarify its potential role in the
      treatment of obesity. 

PMID- 23978583
TI  - Relative importance of phosphorus, fish biomass, and watershed land use as
      drivers of phytoplankton abundance in shallow lakes.
AB  - Phytoplankton abundance in shallow lakes is potentially influenced by ambient
      phosphorus concentrations, nutrient loading accentuated by human activities in
      lake watersheds, and abundance of planktivorous and benthivorous fish. However,
      few studies have simultaneously assessed the relative importance of these factors
      influencing phytoplankton abundance over large spatial scales. We assessed
      relative influences of watershed characteristics, total phosphorus
      concentrations, and fish biomass on phytoplankton abundance in 70 shallow lakes
      in western Minnesota (USA) during summer 2005 and 2006. Our independent variables
      included total phosphorus (TP), benthivore biomass, planktivore biomass, summed
      planktivore and benthivore biomass (summed fish), areal extent of agriculture in
      the watershed, region (prairie versus parkland lakes), and year. Predictive
      models containing from one to three independent variables were compared using an
      information theoretic approach. The most parsimonious model consisted of TP and
      summed fish, and had over 10,000-fold greater support compared to models using
      just TP or summed fish, or models comprised of other variables. We also found no
      evidence that relative importance of predictor variables differed between regions
      or years, and parameter estimates of TP and summed fish were temporally and
      spatially consistent. TP and summed fish were only weakly correlated, and the
      model using both variables was a large improvement over using either variable
      alone. This indicates these two variables can independently increase
      phytoplankton abundance, which emphasizes the importance of managing both
      nutrients and fish when trying to control phytoplankton abundance in shallow
      lakes. 

PMID- 23978584
TI  - Warming-induced changes in denitrifier community structure modulate the ability
      of phototrophic river biofilms to denitrify.
AB  - Microbial denitrification is the main nitrogen removing process in freshwater
      ecosystems. The aim of this study was to show whether and how water warming (+2.5
      degrees C) drives bacterial diversity and structuring and how bacterial
      diversity affects denitrification enzymatic activity in phototrophic river
      biofilms (PRB). We used water warming associated to the immediate thermal release
      of a nuclear power plant cooling circuit to produce natural PRB assemblages on
      glass slides while testing 2 temperatures (mean temperature of 17  degrees C
      versus 19.5  degrees C). PRB were sampled at 2 sampling times during PRB
      accretion (6 and 21days) in both temperatures. Bacterial community composition
      was assessed using ARISA. Denitrifier community abundance and denitrification
      gene mRNA levels were estimated by q-PCR and qRT-PCR, respectively, of 5 genes
      encoding catalytic subunits of the denitrification key enzymes. Denitrification
      enzyme activity (DEA) was measured by the acetylene-block assay at 20  degrees C.
      A mean water warming of 2.5  degrees C was sufficient to produce contrasted total
      bacterial and denitrifier communities and, therefore, to affect DEA. Indirect
      temperature effect on DEA may have varied between sampling time, increasing by up
      to 10 the denitrification rate of 6-day-old PRB and decreasing by up to 5 the
      denitrification rate of 21-day-old PRB. The present results suggest that indirect
      effects of warming through changes in bacterial community composition, coupled to
      the strong direct effect of temperature on DEA already demonstrated in PRB, could
      modulate dissolved nitrogen removal by denitrification in rivers and streams.

PMID- 23978585
TI  - Colloidal stability of nanoparticles derived from simulated cloud-processed
      mineral dusts.
AB  - Laboratory simulation of cloud processing of three model dust types with distinct
      Fe-content (Moroccan dust, Libyan dust and Etna ash) and reference goethite and
      ferrihydrite were conducted in order to gain a better understanding of natural
      nanomaterial inputs and their environmental fate and bioavailability. The
      resulting nanoparticles (NPs) were characterised for Fe dissolution kinetics,
      aggregation/size distribution, micromorphology and colloidal stability of
      particle suspensions using a multi-method approach. We demonstrated that the: (i)
      acid-leachable Fe concentration was highest in volcanic ash (1 m Mg(-1) dust) and
      was followed by Libyan and Moroccan dust with an order of magnitude lower levels;
      (ii) acid leached Fe concentration in the<20 nm fraction was similar in samples
      processed in the dark with those under artificial sunlight, but average
      hydrodynamic diameter of NPs after cloud-processing (pH~6) was larger in the
      former; iii) NPs formed at pH~6 were smaller and less poly-disperse than those at
      low pH, whilst unaltered zeta potentials indicated colloidal instability; iv)
      relative Fe percentage in the finer particles derived from cloud processing does
      not reflect Fe content of unprocessed dusts (e.g. volcanic ash>Libyan dust). The
      common occurrence of Fe-rich "natural nanoparticles" in atmospheric dust derived
      materials may indicate their more ubiquitous presence in the marine environment
      than previously thought.

PMID- 23978586
TI  - Nitrogen inputs to a river course in a heavily impacted watershed: a combined
      hydrochemical and isotopic evaluation (Oglio River Basin, N Italy).
AB  - This study aims at evaluating sources and processes affecting NO3(-)
      concentrations in the Oglio River. Five sampling campaigns considered the main
      watercourse, tributaries, point pollution sources, springs, and groundwater.
      Physico-chemical parameters, N forms, B, Sr(2+), stable isotopes (delta(2)HH2O,
      delta(18)OH2O, delta(15)NNO3, delta(18)ONO3, delta(11)B) and discharge were
      measured. Hydrological modelling was performed using mass balance and End Member
      Mixing Analysis equations. During the irrigation period, in the upstream reach,
      up to 90% of the natural river flow is diverted for irrigation and industrial
      purposes; excess water drained from agricultural fields is returned to river in
      the downstream reach. Results evidenced, in the middle reach, a large input of
      NO3(-)-rich groundwater which could be quantified using hydrological modelling.
      Groundwater inputs are responsible for the sharp, tenfold increase in NO3(-) in
      the river water, from 2.2-4.4 up to 33.5 mgL(-1), and are more evident in summer,
      when discharge is lower. Nevertheless, river water preserves its natural B
      isotopic composition, indicating that the two tracers do not have a common origin
      and are not co-migrant. In the lower plain, surface-groundwater interconnections
      and human disturbances in the water cycle favour the recycling of the compounds
      in the environment, and lead to a similarity in composition of the different
      water bodies (Oglio River, tributaries and groundwater). The long lasting
      agronomical practices have profoundly modified the surface-groundwater
      equilibrium and chemical characteristics, resulting in a highly buffered system.
      Infiltrating irrigation water leaches down NO3(-) which is subsequently
      denitrified; when returned to the Oglio River, groundwater modifies the river
      water composition by dilution, in the case of NO3(-), or by addition, for other
      constituents (e.g. Cl(-), B). The results of this study indicate that, in order
      to reduce the NO3(-) transport towards the Adriatic Sea, groundwater
      contamination should be addressed first, with expected long recovery times.

PMID- 23978587
TI  - Analysis and occurrence of endocrine-disrupting compounds and estrogenic activity
      in the surface waters of Central Spain.
AB  - Endocrine-disrupting compounds (EDCs) are chemical compounds with the ability to
      alter the hormonal systems of organisms. Such compounds are used in several
      industrial and domestic activities and reach the aquatic environment via
      wastewater discharge. The aim of this study is to assess the occurrence of 30
      EDCs and related compounds in the surface waters of central Spain and to
      determine the overall estrogenic activity of environmental samples. This study
      analyzed a large number of EDCs and other emergent or suspected compounds with
      endocrine-disrupting activity. The results have shown the presence of 19 EDCs at
      concentrations ranging from 2 to 5928 ng L(-1). Organophosphorus-based flame
      retardants, alkylphenolic compounds and anticorrosives were found at the highest
      concentrations. Furthermore, although insufficient data are available to
      calculate an average over time, these preliminary results show the need to
      monitor the waters in both rivers studied. Alkylphenolic compounds, particularly
      nonylphenol, were the main contributors to overall estrogenicity. A higher
      concentration of the compounds studied was detected in the river Jarama, although
      the estrogenicity expressed as estradiol equivalents (EEQs) was higher in the
      river Manzanares due to a higher concentration of nonylphenol. However, the total
      estrogenicity did not exceed 1 ng L(-1) (EEQ), which is the level that may cause
      estrogenic effects in aquatic organisms, in any of the samples. In conclusion,
      the potential estrogenic risk in both rivers is low, although organophosphorus
      based flame retardants may increase this risk as they were found at high levels
      in all samples. Unfortunately, these compounds could not be taken into account
      when calculating the estrogenic activity due to the lack of activity data for
      them. For future investigations, it will be important to assess the estrogenicity
      provided by these flame retardants. Due to the significant concentrations of EDCs
      detected in both rivers, further studies in this region are required.

PMID- 23978588
TI  - Fractionation and characterization of humic acids from organic amended rice paddy
      soils.
AB  - Humic acids (HAs), mixture of several complex-structured aromatic and aliphatic
      compounds, are ubiquitous in the terrestrial environment. In this study, HAs were
      fractionated on the basis of their polarity (degree of humification). The
      fractions namely 200P, 300P and 400P were comparatively more humified than
      fractions like 800P and 800S. The application of organic amendments significantly
      increased concentrations of HA fractions especially the more humified fractions
      in rice paddy soils. Among the different fractions, 300P fraction was the most
      abundant in rice paddy soils and its concentration was significantly increased
      due to compost application. The compounds like methyl ketone and 3-phenylprop-2
      enal contributed almost 90% of 300P fraction. 

PMID- 23978590
TI  - Diabetes and cancer--an AACE/ACE consensus statement.

PMID- 23978589
TI  - Tuning the cell fate of neurons and glia by microRNAs.
AB  - The proper function of the nervous system depends on precise production and
      connection of distinct neurons and glia. Cell fate determination of neurons and
      glia is tightly controlled by complex gene expression regulation in the
      developing and adult nervous system. Emerging evidence has demonstrated the
      importance of noncoding microRNAs (miRNAs) in neural development and function.
      This review highlights current discoveries of miRNA functions in specifying
      neuronal and glial cell fate. We summarize the roles of miRNAs in expansion and
      differentiation of neural stem cells, specification of neuronal subtypes and
      glial cells, reprogramming of functional neurons from embryonic stem cells and
      fibroblasts, and left-right asymmetric organization of neuronal subtypes.
      Investigating the network of interactions between miRNAs and target genes will
      reveal new gene regulation machinery involved in tuning the cell fate decisions
      of neurons and glia. 

PMID- 23978592
TI  - Socioeconomic disparities in the operative management of peptic ulcer disease.
AB  - INTRODUCTION: Over the last 60 years, there has been a nationwide decrease in the
      number of operations performed for peptic ulcer disease (PUD). In contrast, the
      experience at our university-based safety net hospital (SNH) was that ulcer
      operations are still performed frequently. We hypothesized that differences in
      frequency of PUD operation may occur in hospitals that serve different patient
      populations. The purpose of this study was to evaluate our experience with PUD
      and compare it with national trends. METHODS: We received institutional review
      board approval and performed this retrospective study of patients undergoing
      operation for PUD between January 2008 and December 2011. Patient records at 2
      hospitals (a private community hospital and a university SNH) with similar
      admission numbers and geographic catchment were examined for PUD risk factors,
      Helicobacter pylori status, insurance/income status, type of operation, and
      surgical outcomes. A case-matched control group of medically treated patients
      were identified after primary diagnosis of PUD by endoscopy at the SNH.
      Univariate and multivariate analyses were performed. RESULTS: The total number of
      operations for PUD performed at the SNH was greater than those performed at the
      private hospital from 2008 to 2011 (142 vs 24; P < .001). The private hospital
      followed national trends over the same time period with a decrease in operations
      for PUD of approximately 93% between 1967 and 2008 (115 to 8 operations per year
      nationally and 119 to 6 at the private hospital). In contrast with the national
      and local private hospital experience, the number of operations for PUD at SNH
      increased from 27 per year in 1985 to 36 per year in 2008. Additionally, 43% of
      patients at the SNH had no insurance, and 61% resided in the poorest quartile of
      zip codes compared with the 3% uninsured patient rate at the private hospital for
      a similar group of patients. At both hospitals, most operations were emergent
      (range, 83-92%) and treated with omental patch (45%), gastric wedge resection
      (15%), vagotomy and antrectomy (19%), or vagotomy and pyloroplasty (14%). At the
      SNH, the H pylori infection rate was less (48% vs 83%; P < .001) and nonsteroidal
      anti-inflammatory drug (NSAID) use was greater (76% vs 63%; P < .01) in the 142
      surgical patients compared with the 320 medical controls. Adjusted risk ratios
      demonstrated insurance status, NSAID use, and lower socioeconomic class were all
      equally predictive of operative ulcer disease when compared with medical
      controls. CONCLUSION: Our study provides 2 observations. First, patients of lower
      socioeconomic standing may have increased rates of complicated PUD owing to
      multiple medical factors and other factors related to healthcare. Second,
      surgical care for PUD retains a clinically important role within this patient
      population.

PMID- 23978591
TI  - Recalcitrant hypocalcemia after thyroidectomy in patients with previous Roux-en-Y
      gastric bypass.
AB  - BACKGROUND: Hypocalcemia is a potential complication after thyroidectomy.
      Patients with previous roux-en-Y gastric bypass (RYGBP) may be at increased risk
      for recalcitrant symptomatic hypocalcemia after thyroidectomy. This complication
      is poorly described and there is no current consensus on optimal management in
      this unique population. METHODS: All patients from 2000 to 2012 who underwent
      thyroidectomy with history of preceding RYGBP were identified retrospectively.
      Each of the 19 patients meeting inclusion criteria were matched 2:1 for age,
      gender, and body mass index (BMI) to a cohort who underwent thyroidectomy without
      previous RYGBP. The study cohort and matched controls were compared for incidence
      of symptomatic postoperative hypocalcemia, requirement of intravenous (IV)
      calcium supplementation, and duration of hospital stay. RESULTS: Age, proportion
      of female patients, and BMI were equivalent between cases (n = 19) and controls
      (n = 38). Comparison of primary outcomes demonstrated that the study group had a
      significantly higher incidence of symptomatic hypocalcemia (42% vs. 0%; P < .01),
      administration of IV calcium (21% vs. 0%; P < .01), and duration of hospital stay
      (2.2 vs. 1.2 days, P = .02). CONCLUSION: Patients with previous RYGBP have a
      greater incidence of recalcitrant symptomatic hypocalcemia after thyroidectomy,
      resulting in prolonged duration of hospital stay. In this patient population,
      calcium levels should be closely monitored and early calcium and vitamin D
      supplementation initiated preemptively.

PMID- 23978593
TI  - Prospective screening in familial nonmedullary thyroid cancer.
AB  - BACKGROUND: Approximately 8% of nonmedullary thyroid cancers are familial. The
      optimal age for screening in familial nonmedullary thyroid cancer (FNMTC) is
      unknown. METHODS: Kindreds with FNMTC (2 or more first-degree relatives affected)
      were screened prospectively with thyroid ultrasonography. RESULTS: Fifteen
      kindreds showed an overall prevalence of thyroid nodule(s) >=5 mm of 44% at
      screening; 19% in the second generation, and 90% in the generation anterior to
      the index case. The youngest age of detection was 10 years for thyroid nodules
      and 18 years for thyroid cancer. Microcalcification of thyroid nodules at
      screening was associated with a greater risk of cancer (P < .05). Family members
      diagnosed with thyroid cancer by ultrasonographic screening were diagnosed at a
      younger age and had a lower rate of extra thyroidal invasion (P < .05).
      CONCLUSION: In FNMTC, first-degree relatives 10 years or older, including the
      generation anterior to the index case, should have thyroid screening by
      ultrasonography, which may result in earlier diagnosis.

PMID- 23978594
TI  - Do giant parathyroid adenomas represent a distinct clinical entity?
AB  - BACKGROUND: The size of abnormal parathyroid glands in patients with primary
      hyperparathyroidism (PHPT) is highly variable, but the clinical significance of
      giant glands is unknown. METHODS: We reviewed 300 consecutive patients after
      parathyroidectomy for PHPT. We compared patients with giant parathyroid adenomas
      (weight >=95th percentile) with the remaining patients. RESULTS: Giant adenomas
      were defined as weight >=95th percentile or 3.5 g (median, 0.61; range, 0.05
      29.93). Patients with giant adenomas had a greater mean preoperative calcium
      level, greater mean parathyroid hormone (PTH) level, and were less likely to have
      multiglandular or symptomatic disease. Giant adenomas were successfully localized
      on imaging in 87% of patients, which was not increased over other patients (82%).
      There were no differences between the groups in age, gender, gland location, or
      the incidence of persistent or recurrent hyperparathyroidism. Finally, giant
      glands had an increased incidence of symptomatic postoperative hypocalcemia,
      including 1 patient who required rehospitalization after removal of a giant
      gland. CONCLUSION: Giant parathyroid adenomas have a distinct presentation
      characterized by single gland disease and lower incidence of symptoms despite
      increased levels of calcium and PTH. Additionally, after resection of a giant
      adenoma, patients are more likely to develop symptomatic hypocalcemia.

PMID- 23978595
TI  - Should eligibility for heart transplantation be a requirement for left
      ventricular assist device use? Recommendations based on a systematic review.
AB  - Left ventricular assist devices (LVADs) are used in chronic end-stage heart
      failure as "bridge to transplantation" (BTT) and, more recently, for transplant
      ineligible patients as "destination therapy" (DT). We reviewed the evidence on
      clinical effects and cost-effectiveness of 2 types of continuous-flow LVADs
      (HeartMate II [HM II] and HeartWare), for BTT and DT patients. We systematically
      searched the scientific literature (January 2008-June 2012) and identified 14
      clinical studies (approximately 2900 HM II and approximately 200 HeartWare
      patients), and 3 economic evaluations (HM II) using simulation models. Data were,
      however, limited to 2-3 studies per outcome. We made policy recommendations on
      the basis of our systematic review. Although complications after implantation are
      frequent, LVAD therapy is often highly effective across transplantation
      eligibility status and device, with 1-year survival reaching 86% for BTT and 78%
      for DT (compared with 25% for medical therapy). Neither BTT nor DT currently meet
      traditional cost-effectiveness limits in models using historical data, although
      BTT is standard practice for a limited number of patients in many regions. We
      found that BTT and DT as implantation strategies tend to be no longer mutually
      exclusive. We conclude that evidence is sufficient to support LVAD use,
      regardless of transplantation eligibility status, as long as patients are
      carefully selected and program infrastructure and budget are adequate. However,
      evidence gaps, limitations in economic models, and the lack of Canadian data
      point to the importance of mandatory, systematic monitoring of LVAD use and
      outcomes. 

PMID- 23978596
TI  - Focused 2012 update of the Canadian Cardiovascular Society guidelines for the use
      of antiplatelet therapy.
AB  - The initial 2010 Canadian Cardiovascular Society (CCS) Guidelines for the Use of
      Antiplatelet Therapy in the Outpatient Setting were published in May 2011. As
      part of a planned re-evaluation within 2 years, we conducted an extensive
      literature search encompassing all topics included in the 2010 CCS Guidelines,
      and concluded that there were sufficient new data to merit revisiting the
      guidance on antiplatelet therapy for secondary prevention in the first year after
      acute coronary syndrome (ACS), percutaneous coronary intervention, or coronary
      artery bypass grafting, and the interaction between clopidogrel and proton pump
      inhibitors. In addition, new clinical trials information about the efficacy and
      safety of combining novel oral anticoagulants with antiplatelet therapy in ACS
      justified the addition of a new section of recommendations to the Guidelines. In
      this focused update, we provide recommendations for the use of clopidogrel,
      ticagrelor, and prasugrel in non-ST elevation ACS, avoidance of prasugrel in
      patients with previous stroke/transient ischemic attack, higher doses of
      clopidogrel (j) /day) for the first 6 days after ACS, and the preferential use of
      prasugrel or ticagrelor after percutaneous coronary intervention in ACS. For non
      ACS stented patients, we recommend acetylsalicylic acid/clopidogrel for 1 year,
      with at least 1 month of therapy for bare-metal stent patients and 3 months for
      drug-eluting stent patients unable to tolerate year-long double therapy. We also
      consider therapy for patients with a history of stent thrombosis, the indications
      for longer-term treatment, discontinuation timing preoperatively, indications for
      changing agents, the management of antiplatelet therapy before and after bypass
      surgery, and use/selection of proton pump inhibitors along with antiplatelet
      agents. 

PMID- 23978597
TI  - Theta oscillations orchestrate medial temporal lobe and neocortex in remembering
      autobiographical memories.
AB  - Remembering autobiographical events can be associated with detailed visual
      imagery. The medial temporal lobe (MTL), precuneus and prefrontal cortex are held
      to jointly enable such vivid retrieval, but how these regions are orchestrated
      remains unclear. An influential prediction from animal physiology is that neural
      oscillations in theta frequency may be important. In this experiment,
      participants prospectively collected audio recordings describing personal
      autobiographical episodes or semantic knowledge over 2 to 7 months. These were
      replayed as memory retrieval cues while recording brain activity with
      magnetoencephalography (MEG). We identified a peak of theta power within a left
      MTL region of interest during both autobiographical and General Semantic
      retrieval. This MTL region was selectively phase-synchronized with theta
      oscillations in precuneus and medial prefrontal cortex, and this synchrony was
      higher during autobiographical as compared to General Semantic knowledge
      retrieval. Higher synchrony also predicted more detailed visual imagery during
      retrieval. Thus, theta phase-synchrony orchestrates in humans the MTL with a
      distributed neocortical memory network when vividly remembering autobiographical
      experiences.

PMID- 23978598
TI  - Ecological risks of polycyclic musk in soils irrigated with reclaimed municipal
      wastewater.
AB  - HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8-hexamethylcyclopenta-c-2-benzopyrane) and
      AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene) are found in
      reclaimed municipal wastewater. They may accumulate in soils receiving long-term
      application of reclaimed water thus adversely impact the soil biota. We evaluated
      the extent of their accumulation in receiving soils using HYDRUS-1D based on
      reclaimed municipal wastewater irrigation data at a public park in Beijing. The
      potential for ecological harms were assessed according to tested and reported
      outcomes of acute toxicity tests using wheat (Triticum aetivum L), earthworm
      (Eisenia fetida) and springtail (Bourletiella hortensis) as target organisms.
      Results of comparison among EC50 values from wheat, earthworm and springtail
      showed the EC50 value for root elongation inhibition of wheat germination was the
      least. Based on the least EC50, predicted no effect concentration in soils were
      290 and 320ng /g for HHCB and ATHN, respectively. Comparable results from
      simulation to experimental and field investigating date validated the using of
      HYDRUS-1D in the work. Results of risk prediction showed it would take 243 and
      666 years for HHCB and AHTN accumulated in soils at current irrigation practice
      to reach the levels for the resulting risk characterization ratios (RCRs) to
      cause potential ecosystem harms. 

PMID- 23978599
TI  - A crystallin gene network in the mouse retina.
AB  - The present study was designed to examine the regulation of crystallin genes and
      protein in the mouse retina using the BXD recombinant inbred (RI) strains.
      Illumina Sentrix BeadChip Arrays (MouseWG-6v2) were used to analyze mRNA levels
      in 75 BXD RI strains along with the parental strains (C57Bl/6J and DBA/2J), and
      the reciprocal crosses in the Hamilton Eye Institute (HEI) Retina Dataset
      (www.genenetwork.org). Protein levels were investigated using immunoblots to
      quantify levels of proteins and indirect immunohistochemistry to define the
      distribution of protein. Algorithms in the Genomatix program were used to
      identify transcription factor binding sites common to the regulatory sequences in
      the 5' regions of co-regulated set of crystallin and other genes as compared to a
      set of control genes. As subset of genes, including many encoding lens
      crystallins is part of a tightly co-regulated network that is active in the
      retina. Expression of this crystallin network appears to be binary in nature,
      being expressed either at relatively low levels or being highly upregulated.
      Relative to a control set of genes, the 5' regulatory sequences of the crystallin
      network genes show an increased frequency of a set of common transcription factor
      binding sites, the most common being those of the Maf family. Chromatin
      immunoprecipitation of human lens epithelial cells (HLEC) and rat retinal
      ganglion cells (RGC) confirmed the functionality of these sites, showing that
      MafA binds the predicted sites of CRYGA and CRYGD in HLE and CRYAB, CRYGA,
      CRYBA1, and CRYBB3 in RGC cells. In the retina there is a highly correlated group
      of genes containing many members of the alpha- beta- and gamma-crystallin
      families. These genes can be dramatically upregulated in the retina. One
      transcription factor that appears to be involved in this coordinated expression
      is the MAF family transcription of factors associated with both lens and
      extralenticular expression of crystallin genes. 

PMID- 23978601
TI  - The effects of time, luminance, and high contrast targets: revisiting grating
      acuity in the domestic cat.
AB  - Based on optical clarity and retinal cone density, the cat has a potential acuity
      of 20-30 cycles per degree (cpd), yet most behavioral studies estimate feline
      acuity between 3 and 9 cpd. Those studies, however, were limited by restrictive
      experimental conditions that may have inadvertently lowered the estimated grating
      acuity. Two domestic cats previously trained on a two-choice visual
      discrimination task were retrained on a grating detection/discrimination task
      with unlimited time, high luminance, high contrast targets, and adequate space to
      prevent poor accommodation from affecting the results. Initially, vertical
      gratings of increasing cpd were tested until failure. Then, horizontal gratings
      of increasing cpd were tested until failure. Finally, the finest horizontal
      grating resolved was confirmed with a third test requiring 24 correct out of 36
      consecutive trials, yielding a binomial probability less than 0.02 of non-random
      occurrence. M1, a 7-year-old male gray tabby with +2.00 OU refraction, tested for
      a grating detection acuity of 15 cpd for both vertical and horizontal gratings
      (binomial probability = 0.009). F1, a 2-year-old female gray tabby with +0.25 OU
      refraction, tested for a grating orientation discrimination acuity of 20 cpd for
      both vertical and horizontal gratings (binomial probability = 0.004). These
      results demonstrate that a young cat with good focus is capable of discriminating
      20 cpd, in close agreement with the physiologic maximum. Uncorrected focusing
      errors appear to degrade visual performance. Optimum experimental conditions
      resulted in better grating acuity measurements than previously reported,
      emphasizing the importance of environmental factors in feline behavioral testing.

PMID- 23978602
TI  - The usefulness of olfactory fear conditioning for the study of early emotional
      and cognitive impairment in reserpine model.
AB  - Due to the ability for depleting neuronal storages of monoamines, the reserpine
      model is a suitable approach for the investigation of the neurobiology of
      neurodegenerative diseases. However, the behavioral effects of low doses of
      reserpine are not always detected by classic animal tests of cognition, emotion,
      and sensory ability. In this study, the effects of reserpine (0.5-1.0mg/kg) were
      evaluated in olfactory fear conditioning, inhibitory avoidance, open-field,
      elevated plus-maze, and olfactory discrimination. Possible protective effects
      were also investigated. We found that single administration of reserpine impaired
      the acquisition of olfactory fear conditioning (in both doses) as well as
      olfactory discrimination (in the higher dose), while no effects were seen in all
      other tests. Additionally, we demonstrated that prior exposure to environmental
      enrichment prevented effects of reserpine in animals tested in olfactory fear
      conditioning. Altogether, these findings suggest that a combined cognitive,
      emotional and sensory-dependent task would be more sensitive to the effects of
      the reserpine model. In addition, the present data support the environmental
      enrichment as an useful approach for the study of resilience mechanisms in
      neurodegenerative processes. 

PMID- 23978600
TI  - Nanoceria inhibit expression of genes associated with inflammation and
      angiogenesis in the retina of Vldlr null mice.
AB  - Oxidative stress and inflammation are important pathological mechanisms in many
      neurodegenerative diseases, including age-related macular degeneration (AMD). The
      very low-density lipoprotein receptor knockout mouse (Vldlr-/-) has been
      identified as a model for AMD and in particular for retinal angiomatous
      proliferation (RAP). In this study we examined the effect of cerium oxide
      nanoparticles (nanoceria) that have been shown to have catalytic antioxidant
      activity, on expression of 88 major cytokines in the retinas of Vldlr-/- mice
      using a PCR array. A single intravitreal injection of nanoceria at P28 caused
      inhibition of pro-inflammatory cytokines and pro-angiogenic growth factors
      including Tslp, Lif, Il3, Il7, Vegfa, Fgf1, Fgf2, Fgf7, Egf, Efna3, Lep, and up
      regulation of several cytokines and anti-angiogenic genes in the Vldlr-/- retina
      within one week. We used the Ingenuity Pathway Analysis software to search for
      biological functions, pathways, and interrelationships between gene networks.
      Many of the genes whose activities were affected are involved in cell signaling,
      cellular development, growth and proliferation, and tissue development. Western
      blot analysis revealed that nanoceria inhibit the activation of ERK 1/2, JNK, p38
      MAP kinase, and Akt. These data suggest that nanoceria may represent a novel
      therapeutic strategy to treat AMD, RAP, and other neurodegenerative diseases. 

PMID- 23978603
TI  - Study of the influence of temperature and precipitations on the levels of BTEX in
      natural waters.
AB  - Assessment of seasonal changes in surface water quality is an important aspect
      for evaluating temporal variation of water due to natural or anthropogenic inputs
      of point and non-point sources. The objective of this paper was to investigate
      the influence of seasonal temperature fluctuations and precipitations on the
      levels of BTEX in natural waters. Principal component analysis (PCA) was used to
      evaluate the seasonal correlations of BTEX levels in water and to extract the
      parameters that are most important in assessing seasonal variations of water
      quality. This study was carried out as a part of VOCs monitoring program in
      natural water samples from Mediterranean coast. To carry out this project, a
      multiresidue analytical method was used. The method was based on headspace solid
      phase microextraction (HS-SPME) followed by gas chromatography coupled to flame
      ionization detector (FID). The limits of detection LODs found for the tested
      analyte tested were in the 0.001-1 MUg/L range. These values were adequate for
      the analysis of these compounds in water samples according to the regulated
      values. Water samples from different points of the Mediterranean coast were
      analyzed during a period of three years, and were taken four times per year. Most
      of the compounds were below the limit established by the legislation. The results
      obtained by a chemometric study indicated that temperature and precipitations can
      be related on the BTEX levels found in water. A regression model between
      temperature or precipitations and BTEX concentration was obtained, thus these
      models can be used as predictive model for detection any non-normal concentration
      level.

PMID- 23978604
TI  - A 10-year, single-institution analysis of clinicopathologic features and sentinel
      lymph node biopsy in thin melanomas.
AB  - BACKGROUND: The 2009 American Joint Committee on Cancer criteria for thin
      cutaneous melanomas recommend staging sentinel lymph node (SLN) biopsy (SLNB) for
      select stage IB tumors. SLNB in this population remains controversial because of
      low rates of node positivity and inconsistent prognostic parameters. OBJECTIVE:
      The purpose of this study was to examine the association between multiple
      clinicopathologic features and SLNB result, and clinical outcome. METHODS:
      Clinical and pathologic parameters from patients with melanomas less than or
      equal to 1.00 mm receiving wide local excision with SLNB at our institution from
      2001 through 2010 were recorded. Analysis for any statistically significant
      relationships between recorded parameters and SLN results and outcome were
      performed. RESULTS: A total of 189 cases yielded 3 positive SLNBs (1.6%). Disease
      progression occurred in 6 cases (3.2%). Positive SLNB predicted distant
      metastasis and death from disease (P = .0017). Mitotic rate was not associated
      with a positive SLNB result. LIMITATIONS: The follow-up time for this study was
      limited (mean = 40.7 months). CONCLUSION: Our data confirm a statistically
      significant relationship between SLNB result and likelihood for distant
      metastasis in thin melanoma. There was a trend for a relationship between mitotic
      rate and clinical outcome. This relationship reached statistical significance at
      a mitotic rate of greater than 3 mitoses/mm(2).

PMID- 23978605
TI  - Comparison of SPF10 real-time PCR and conventional PCR in combination with the
      INNO-LiPA HPV Genotyping Extra assay for the detection and typing of human
      papillomavirus in cervical samples.
AB  - The novel SPF10 real-time PCR assay allows the simultaneous amplification and
      detection of the HPV target. That way, LiPA analysis of the HPV-negative samples
      can be avoided, reducing workload and cost. This study aims to evaluate the
      performance of the SPF10 real-time PCR in combination with the LiPA assay for HPV
      detection and typing in cervical samples. Thirty-nine cervical samples were
      subjected to the SPF10 conventional PCR in combination with the LiPA assay.
      Subsequently, the SPF10 real-time PCR was performed to enable the comparison
      between the SPF10 conventional and the real-time PCR results. In case of
      discrepancy, the samples were subjected to the CLART HPV2 assay. As a result, 27
      out of 39 samples were identified as HPV-positive by the SPF10 real-time PCR and
      were genotyped further by the LiPA assay. Twenty samples (74.1%) showed an
      absolute agreement between the conventional and real-time SPF10 PCR (concordant),
      three (11.1%) displayed additional or fewer types (compatible), two (7.4%) did
      not show any similarity between both assays (discordant) and the remaining two
      (7.4%) were LiPA-negative. The two assays showed an excellent strength of
      agreement for individual (kappa=0.932) and multiple genotype detection
      (kappa=0.834). In conclusion, the two SPF10 PCR methods are comparable.
      Therefore, the SPF10 real-time PCR with subsequent LiPA could be used for the
      detection and genotyping of HPV in cervical samples.

PMID- 23978606
TI  - Design and modeling of sustainable bioethanol supply chain by minimizing the
      total ecological footprint in life cycle perspective.
AB  - The purpose of this paper is to develop a model for designing the most
      sustainable bioethanol supply chain. Taking into consideration of the possibility
      of multiple-feedstock, multiple transportation modes, multiple alternative
      technologies, multiple transport patterns and multiple waste disposal manners in
      bioethanol systems, this study developed a model for designing the most
      sustainable bioethanol supply chain by minimizing the total ecological footprint
      under some prerequisite constraints including satisfying the goal of the
      stakeholders', the limitation of resources and energy, the capacity of
      warehouses, the market demand and some technological constraints. And an
      illustrative case of multiple-feedstock bioethanol system has been studied by the
      proposed method, and a global best solution by which the total ecological
      footprint is the minimal has been obtained. 

PMID- 23978607
TI  - Life-cycle analysis of bio-based aviation fuels.
AB  - Well-to-wake (WTWa) analysis of bio-based aviation fuels, including
      hydroprocessed renewable jet (HRJ) from various oil seeds, Fischer-Tropsch jet
      (FTJ) from corn-stover and co-feeding of coal and corn-stover, and pyrolysis jet
      from corn stover, is conducted and compared with petroleum jet. WTWa GHG emission
      reductions relative to petroleum jet can be 41-63% for HRJ, 68-76% for pyrolysis
      jet and 89% for FTJ from corn stover. The HRJ production stage dominates WTWa GHG
      emissions from HRJ pathways. The differences in GHG emissions from HRJ production
      stage among considered feedstocks are much smaller than those from fertilizer use
      and N2O emissions related to feedstock collection stage. Sensitivity analyses on
      FTJ production from coal and corn-stover are also conducted, showing the
      importance of biomass share in the feedstock, carbon capture and sequestration
      options, and overall efficiency. For both HRJ and FTJ, co-product handling
      methods have significant impacts on WTWa results. 

PMID- 23978608
TI  - Bioleaching of heavy metal from woody biochar using Acidithiobacillus
      ferrooxidans and activation for adsorption.
AB  - A woody biochar which was the byproduct of gasification of sawdust was treated
      with bioleaching by Acidithiobacillus ferrooxidans. After bioleaching, most heavy
      metal was removed from biochar. Leaching efficiency of heavy metal was efficient
      in a wide pulp density range from 1% to 10% (w/v) and decreased only a little
      with the increase in pulp density. It made application of biochar free of heavy
      metal risk. Benefitting from the improvement in functional group composition and
      pore structure after bioleaching, adsorption capacity of biochar to methylene
      blue and heavy metal was enhanced greatly. Adsorption of methylene blue could be
      described by pseudo-second-order model and Langmuir equation and the enhancement
      was mainly caused by the modification of physical character of biochar.
      Adsorption of heavy metal could be described by Freundlich equation and was
      mainly determined by chemical character of biochar. 

PMID- 23978609
TI  - Predicting efficiency of use of metabolizable energy to net energy for gain and
      maintenance of Nellore cattle.
AB  - Twenty-six comparative slaughter studies were used (n = 752 animals) and coded
      within each experiment by gender (431 bulls, 204 steers, and 117 heifers) and
      breed (447 Nellore and 305 Bos indicus and Bos taurus crossbreds) to develop
      equations to predict the efficiency of use of ME to NE for growth (kg) and ME to
      NE for maintenance (km). The retained energy (RE) was regressed on ME intake
      (MEI) available for gain using orthogonal regression to obtain the kg within each
      experiment. The estimated kg was regressed on RE as protein (REp) according to
      the following equation: kg = a/(b + REp). Gender and breed effects were not
      tested because of limited number of experiments. The km was estimated as the
      intercept of the following equation: HP = beta0 * e((beta1 * MEI)), in which HP
      is heat production, beta0 and beta1 are coefficients, and e is the natural
      logarithm. The ME for maintenance (MEm) was computed assuming MEI equals to HP at
      maintenance. The km was obtained using the stepwise procedure of a multiple
      regression including ADG, empty body gain (EBG), empty BW (EBW), EBW(0.75), kg,
      and energy content in the EBW. A random coefficient model, assuming a random
      variation for study effects, was used to test breed and gender effects to
      identify the best model to estimate km. The overall equation to predict kg was
      0.327 (+/-0.142)/[0.539 (+/-0.317) + REp], with an R(2) of 0.963. The equation to
      predict km was 0.513 (+/-0.024) + 0.173 (+/-0.061) * kg + a * EBG, R(2) = 0.92,
      in which a = 0.100 (+/-0.021) for B. indicus or a = 0.073 (+/-0.021) for
      crossbreds. Our results indicated that B. indicus were more efficient to use ME
      for maintenance. We concluded that km can be predicted from kg and EBG and that
      B. indicus * B. taurus crossbreds can affect km. Furthermore, kg can be predicted
      from REp and neither gender nor crossbreeding (B. indicus * B. taurus) affected
      kg. Because our database consisted of Nellore and B. indicus and B. taurus
      crossbreds, it is necessary to further evaluate differences between B. taurus and
      B. indicus regarding the kg. 

PMID- 23978611
TI  - Insights into significant pathways and gene interaction networks underlying
      breast cancer cell line MCF-7 treated with 17beta-estradiol (E2).
AB  - OBJECTIVE: Estrogens are known to regulate the proliferation of breast cancer
      cells and to alter their cytoarchitectural and phenotypic properties, but the
      gene networks and pathways by which estrogenic hormones regulate these events are
      only partially understood. METHODS: We used global gene expression profiling by
      Affymetrix GeneChip microarray analysis, with KEGG pathway enrichment, PPI
      network construction, module analysis and text mining methods to identify
      patterns and time courses of genes that are either stimulated or inhibited by
      estradiol (E2) in estrogen receptor (ER)-positive MCF-7 human breast cancer
      cells. RESULTS: Of the genes queried on the Affymetrix Human Genome U133 plus 2.0
      microarray, we identified 628 (12h), 852 (24h) and 880 (48 h) differentially
      expressed genes (DEGs) that showed a robust pattern of regulation by E2. From
      pathway enrichment analysis, we found out the changes of metabolic pathways of E2
      treated samples at each time point. At 12h time point, the changes of metabolic
      pathways were mainly focused on pathways in cancer, focal adhesion, and chemokine
      signaling pathway. At 24h time point, the changes were mainly enriched in
      neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction
      and calcium signaling pathway. At 48 h time point, the significant pathways were
      pathways in cancer, regulation of actin cytoskeleton, cell adhesion molecules
      (CAMs), axon guidance and ErbB signaling pathway. Of interest, our PPI network
      analysis and module analysis found that E2 treatment induced enhancement of
      PRSS23 at the three time points and PRSS23 was in the central position of each
      module. Text mining results showed that the important genes of DEGs have
      relationship with signal pathways, such as ERbB pathway (AREG), Wnt pathway
      (NDP), MAPK pathway (NTRK3, TH), IP3 pathway (TRA@) and some transcript factors
      (TCF4, MAF). CONCLUSIONS: Our studies highlight the diverse gene networks and
      metabolic and cell regulatory pathways through which E2 operates to achieve its
      widespread effects on breast cancer cells.

PMID- 23978612
TI  - Transcriptome analysis and SNP identification in SCC of horn in (Bos indicus)
      Indian cattle.
AB  - Single Nucleotide Polymorphisms (SNPs) have become the marker of choice for
      genome wide association studies. In order to provide the best genome coverage for
      the analysis of disease, production and performance traits, a large number of
      relatively evenly distributed SNPs are needed. The main objective of present work
      was to identify large numbers of gene-associated SNPs using high-throughput
      sequencing in squamous cell carcinoma of horn. RNA-seq analysis was conducted on
      2 tissues viz. Horn Cancer (HC) and Horn Normal (HN) in Kankrej breed of cattle.
      A total of 909,362 reads with average read length of 405 bp for HC and 583,491
      reads with average read length of 411 bp for HN were obtained. We found 9532 and
      7065 SNPs as well as 1771 and 1172 Indels in HC and HN, respectively, from which,
      7889 SNPs and 1736 Indels were uniquely present in HC, 5886 SNPs and 1146 Indels
      were uniquely present in HN and reported first time in Bos indicus, whereas the
      rest are already reported in Bos taurus dbSNP database. The gene-associated SNPs
      and Indels were high in upregulated genes of HC as compared to HN. Analysis of
      differentially expressed genes was identified, these genes are involved in
      regulation of cell proliferation, apoptosis, gene transcription, cell survival
      and metabolism through various metabolic pathways. The result of transcriptome
      expression profiling was validated using Real Time quantitative PCR in nine
      randomly selected genes. We identified numbers aberrant signaling pathways
      responsible for carcinogenesis in HC which are also commonly altered in squamous
      cell carcinoma (SCC) of lung in human being. We conclude that a large number of
      altered genes and dysfunction of multiple pathways are involved in the
      development of Horn Cancer. The present findings contribute to theoretical
      information for further screening of genes and identification of markers for
      early diagnosis of HC as well as SNPs identified in this report provide a much
      needed resource for genetic studies in B. indicus and shall contribute to the
      development of a high density SNP array. Validation and testing of these SNPs
      using SNP arrays will form the material basis for gene associated SNPs in HC.

PMID- 23978613
TI  - Grouping and characterization of putative glycosyltransferase genes from Panax
      ginseng Meyer.
AB  - Glycosyltransferases are members of the multigene family of plants that can
      transfer single or multiple activated sugars to a range of plant molecules,
      resulting in the glycosylation of plant compounds. Although the activities of
      many glycosyltransferases and their products have been recognized for a long
      time, only in recent years were some glycosyltransferase genes identified and few
      have been functionally characterized in detail. Korean ginseng (Panax ginseng
      Meyer), belonging to Araliaceae, has been well known as a popular mysterious
      medicinal herb in East Asia for over 2,000 years. A total of 704
      glycosyltransferase unique sequences have been found from a ginseng expressed
      sequence tag (EST) library, and these sequences encode enzymes responsible for
      the secondary metabolite biosynthesis. Finally, twelve UDP glycosyltransferases
      (UGTs) were selected as the candidates most likely to be involved in triterpenoid
      synthesis. In this study, we classified the candidate P. ginseng UGTs (PgUGTs)
      into proper families and groups, which resulted in eight UGT families and six UGT
      groups. We also investigated those gene candidates encoding for
      glycosyltransferases by analysis of gene expression in methyl jasmonate (MeJA)
      treated ginseng adventitious roots and different tissues from four-year-old
      ginseng using quantitative reverse transcriptase-polymerase chain reaction (RT
      PCR). For organ-specific expression, most of PgUGT transcription levels were
      higher in leaves and roots compared with flower buds and stems. The transcription
      of PgUGTs in adventitious roots treated with MeJA increased as compared with the
      control. PgUGT1 and PgUGT2, which belong to the UGT71 family genes expressed in
      MeJA-treated adventitious roots, were especially sensitive, showing 33.32 and
      38.88-fold expression increases upon 24h post-treatments, respectively.

PMID- 23978614
TI  - Identification and characterization of novel alternative splice variants of human
      SAMD11.
AB  - Sterile alpha motif domain-containing 11 (SAMD11) is evolutionarily conserved
      from zebrafish to human. Mouse Samd11 is predominantly expressed in developing
      retinal photoreceptors and the adult pineal gland, and its transcription is
      directly regulated by the cone-rod homeodomain protein Crx. However, there has
      been little research on human SAMD11. To investigate the function of human
      SAMD11, we first cloned its coding sequence (CDS) and identified up to 45 novel
      alternative splice variants (ASVs). Mouse Samd11 ASVs were also identified by
      aligning the mouse Samd11 expressed sequence tags (ESTs) with the annotated
      sequence. However, the range of expression and transcriptional regulation of
      SAMD11 differs between human and mouse. Human SAMD11 was found to be widely
      expressed in many cell lines and ocular tissues and its transcription was not
      regulated by CRX, OTX2 or NR2E3 proteins. Furthermore, functional analysis
      indicated that human SAMD11 could promote cell proliferation slightly. In
      conclusion, this study elucidated the basic characteristics of human SAMD11 and
      revealed that, although the occurrence of alternative splicing of SAMD11 was
      conserved, the function of SAMD11 may vary in different species.

PMID- 23978616
TI  - Protoporphyrin IX-mediated sonodynamic action induces apoptosis of K562 cells.
AB  - OBJECTIVES: The present study aims to investigate apoptosis of human leukemia
      K562 cells induced by protoporphyrin IX (PpIX)-mediated sonodynamic therapy (PpIX
      SDT). METHODS: The uptakes of intracellular PpIX in K562 cells were detected by
      flow cytometry. The sub-cellular localization of PpIX was imaged by confocal
      microscope. The cytotoxic effect of PpIX-SDT was assessed by MTT (3-(4,5
      dimethylthiazol-2-yl)-2, 5-diphenylter-trazolium bromide tetrazolium) assay.
      Apoptosis was evaluated by chromatin condensation with DAPI (4'-6-diamidino-2
      phenylindole) staining, decrease of mitochondria membrane potential (MMP), re
      distribution of Bax, and the expression changes of the key apoptosis-associated
      protein (Caspase-3 and polypeptide poly (ADP-robose) polymerase). The possible
      mechanism of SDT-induced apoptosis was investigated by detecting by intracellular
      ROS (reactive oxygen species) generation and effect of ROS scavenger-NAC (N
      acetylcysteine) on SDT induced apoptosis. RESULTS: The intracellular PpIX
      increased quickly within 2 h after PpIX administration and PpIX mainly localized
      in the mitochondria. Compared with PpIX alone and ultrasound alone groups, the
      synergistic cytotoxicity of PpIX plus ultrasound was significantly boosted. In
      addition, the ultrasound induced some extent of chromatin condensation and MMP
      loss was greatly enhanced by the presence of 2 MUg/ml PpIX, where PpIX alone
      treatment showed no or only slight effect. Time-dependent Bax translocation,
      caspase-3 activation and PARP cleavage were detected in SDT treatment groups.
      Besides, intracellular ROS production was significantly enhanced after SDT, and
      the general ROS scavenger NAC could obviously alleviate the SDT-caused cell
      viability loss, MMP loss, Bax redistribution and nuclear changes. CONCLUSIONS:
      These results indicated that PpIX-mediated sonodynamic action could induce
      apoptosis on K562 cells, and the intracellular ROS was involved in the PpIX-SDT
      induced apoptosis.

PMID- 23978615
TI  - Dorsal column sensory axons degenerate due to impaired microvascular perfusion
      after spinal cord injury in rats.
AB  - The mechanisms contributing to axon loss after spinal cord injury (SCI) are
      largely unknown but may involve microvascular loss as we have previously
      suggested. Here, we used a mild contusive injury (120 kdyn IH impactor) at T9 in
      rats focusing on ascending primary sensory dorsal column axons, anterogradely
      traced from the sciatic nerves. The injury caused a rapid and progressive loss of
      dorsal column microvasculature and oligodendrocytes at the injury site and
      penumbra and an ~70% loss of the sensory axons by 24 h. To model the
      microvascular loss, focal ischemia of the T9 dorsal columns was achieved via
      phototoxic activation of intravenously injected rose bengal. This caused an ~53%
      loss of sensory axons and an ~80% loss of dorsal column oligodendrocytes by 24 h.
      Axon loss correlated with the extent and axial length of microvessel and
      oligodendrocyte loss along the dorsal column. To determine if oligodendrocyte
      loss contributes to axon loss, the glial toxin ethidium bromide (EB; 0.3 MUg/MUl)
      was microinjected into the T9 dorsal columns, and resulted in an ~88% loss of
      dorsal column oligodendrocytes and an ~56% loss of sensory axons after 72 h. EB
      also caused an ~75% loss of microvessels. Lower concentrations of EB resulted in
      less axon, oligodendrocyte and microvessel loss, which were highly correlated
      (R(2) = 0.81). These data suggest that focal spinal cord ischemia causes both
      oligodendrocyte and axon degeneration, which are perhaps linked. Importantly,
      they highlight the need of limiting the penumbral spread of ischemia and
      oligodendrocyte loss after SCI in order to protect axons.

PMID- 23978617
TI  - Material damage diagnosis and characterization for turbine rotors using three
      dimensional adaptive ultrasonic NDE data reconstruction techniques.
AB  - Damage diagnosis for turbine rotors plays an essential role in power plant
      management. Ultrasonic non-destructive examinations (NDEs) have increasingly been
      utilized as an effective tool to provide comprehensive information for damage
      diagnosis. This study presents a general methodology of damage diagnosis for
      turbine rotors using three-dimensional adaptive ultrasonic NDE data
      reconstruction techniques. Volume reconstruction algorithms and data fusion
      schemes are proposed to map raw ultrasonic NDE data back to the structural model
      of the object being examined. The reconstructed volume is used for automatic
      damage identification and quantification using region-growing algorithms and the
      method of distance-gain-size. Key reconstruction parameters are discussed and
      suggested based on industrial experiences. A software tool called AutoNDE Rotor
      is developed to automate the overall analysis workflow. Effectiveness of the
      proposed methods and AutoNDE Rotor are explored using realistic ultrasonic NDE
      data. 

PMID- 23978619
TI  - A spatial web/agent-based model to support stakeholders' negotiation regarding
      land development.
AB  - Decision making in land management can be greatly enhanced if the perspectives of
      concerned stakeholders are taken into consideration. This often implies
      negotiation in order to reach an agreement based on the examination of multiple
      alternatives. This paper describes a spatial web/agent-based modeling system that
      was developed to support the negotiation process of stakeholders regarding land
      development in southern Alberta, Canada. This system integrates a fuzzy analytic
      hierarchy procedure within an agent-based model in an interactive visualization
      environment provided through a web interface to facilitate the learning and
      negotiation of the stakeholders. In the pre-negotiation phase, the stakeholders
      compare their evaluation criteria using linguistic expressions. Due to the
      uncertainty and fuzzy nature of such comparisons, a fuzzy Analytic Hierarchy
      Process is then used to prioritize the criteria. The negotiation starts by a
      development plan being submitted by a user (stakeholder) through the web
      interface. An agent called the proposer, which represents the proposer of the
      plan, receives this plan and starts negotiating with all other agents. The
      negotiation is conducted in a step-wise manner where the agents change their
      attitudes by assigning a new set of weights to their criteria. If an agreement is
      not achieved, a new location for development is proposed by the proposer agent.
      This process is repeated until a location is found that satisfies all agents to a
      certain predefined degree. To evaluate the performance of the model, the
      negotiation was simulated with four agents, one of which being the proposer
      agent, using two hypothetical development plans. The first plan was selected
      randomly; the other one was chosen in an area that is of high importance to one
      of the agents. While the agents managed to achieve an agreement about the
      location of the land development after three rounds of negotiation in the first
      scenario, seven rounds were required in the second scenario. The proposed
      web/agent-based model facilitates the interaction and learning among stakeholders
      when facing multiple alternatives. 

PMID- 23978618
TI  - Consumers' perceptions of patient-accessible electronic medical records.
AB  - BACKGROUND: Electronic health information (eHealth) tools for patients, including
      patient-accessible electronic medical records (patient portals), are
      proliferating in health care delivery systems nationally. However, there has been
      very limited study of the perceived utility and functionality of portals, as well
      as limited assessment of these systems by vulnerable (low education level,
      racial/ethnic minority) consumers. OBJECTIVE: The objective of the study was to
      identify vulnerable consumers' response to patient portals, their perceived
      utility and value, as well as their reactions to specific portal functions.
      METHODS: This qualitative study used 4 focus groups with 28 low education level,
      English-speaking consumers in June and July 2010, in New York City. RESULTS:
      Participants included 10 males and 18 females, ranging in age from 21-63 years;
      19 non-Hispanic black, 7 Hispanic, 1 non-Hispanic White and 1 Other. None of the
      participants had higher than a high school level education, and 13 had less than
      a high school education. All participants had experience with computers and 26
      used the Internet. Major themes were enhanced consumer engagement/patient
      empowerment, extending the doctor's visit/enhancing communication with health
      care providers, literacy and health literacy factors, improved prevention and
      health maintenance, and privacy and security concerns. Consumers were also asked
      to comment on a number of key portal features. Consumers were most positive about
      features that increased convenience, such as making appointments and refilling
      prescriptions. Consumers raised concerns about a number of potential barriers to
      usage, such as complex language, complex visual layouts, and poor usability
      features. CONCLUSIONS: Most consumers were enthusiastic about patient portals and
      perceived that they had great utility and value. Study findings suggest that for
      patient portals to be effective for all consumers, portals must be designed to be
      easy to read, visually engaging, and have user-friendly navigation.

PMID- 23978620
TI  - Decolorization of the metal textile dye Lanaset Grey G by immobilized white-rot
      fungi.
AB  - In this paper we studied the ability of four Tunisian-isolated fungi (i.e.
      Coriolopsis gallica, Bjerkandera adusta, Trametes versicolor and Trametes trogii)
      immobilized into Ca-alginate beads to decolorize the metal textile dye Lanaset
      Grey G (LG). The effect of different operational conditions, such as initial dye
      concentration, temperature, pH, beads/medium ratio and agitation, on dye
      decolorization by the immobilized fungi was investigated. Maximal decolorization
      percentages of 88.7%, 89.3%, 82.1% and 81.3% for C. gallica, B. adusta, T.
      versicolor and T. trogii were attained, respectively, when operating at an
      initial LG concentration of 150 mg/L, pH values of 5.0-6.0, temperatures of 40-45
      degrees C and a beads/medium ratio of 20% (w/v) in static conditions after 72 h
      of incubation. Subsequently, the re-usability of the immobilized fungi was
      evaluated. After three decolorization cycles, the decolorization percentage of
      free cell cultures dropped to values below 36%, while decolorization percentages
      of about 75%, 70%, 60% and 68% were obtained by the immobilized cultures of C.
      gallica, B. adusta, T. versicolor and T. trogii, respectively. 

PMID- 23978621
TI  - Influence of background particulate matter (PM) on urban air quality in the
      Pacific Northwest.
AB  - Elevated particulate matter concentrations due to Asian long-range transport
      (LRT) are frequently observed in the free troposphere (FT) above the Pacific
      Northwest, U.S. Transport of this aerosol from the FT to the boundary layer (BL)
      and its effect to local air quality remain poorly constrained. We used data
      collected at the Mount Bachelor observatory (MBO, 2.8 km a.s.l) and from ground
      stations in the Pacific Northwest to study transport of fine particulate matter
      (PM) from the FT to the BL. During Asian LRT episodes PM concentrations were
      clearly elevated above the corresponding monthly averages at MBO as well as at
      low elevation sites across Washington and Oregon. Also, a clear correlation
      between MBO and low elevation sites was observed, indicating that LRT episodes
      are seen in both the FT and BL. In addition, drum impactor measurements show that
      the chemical composition of PM at MBO was similar to that measured at the BL
      sites. Using a simple regression model, we estimate that during springtime, when
      the transport from Asia is most effective, the contribution of Asian sources to
      PM2.5 in clean background areas of the Pacific Northwest was on average 1.7 MUg
      m(-3) (representing approximately 50-80% of PM). The influence of LRT PM was also
      seen in measurement stations situated in the urban and urban background areas.
      However, the fraction of LRT PM was less pronounced (36-50% of PM) due to larger
      local emissions in the urban areas. 

PMID- 23978622
TI  - Choroidal lymphoma: clinical features and association with systemic lymphoma.
AB  - PURPOSE: To describe the clinical and histopathologic features of choroidal
      lymphoma (CL) and its association with systemic lymphoma. DESIGN: Observational
      case series. PARTICIPANTS: Fifty-nine patients (73 eyes) with CL. METHODS:
      Retrospective chart review. MAIN OUTCOME MEASURES: Clinical features,
      histopathology, and systemic lymphoma. RESULTS: Of 59 patients with CL, systemic
      lymphoma was absent in 41 (primary CL; 69%) and present in 18 (secondary CL;
      31%). Of 18 patients with systemic lymphoma at presentation, 14 (78%) had known
      systemic lymphoma and 4 (22%) were diagnosed with systemic lymphoma shortly after
      presentation. The most common types of systemic lymphoma in patients with
      secondary CL were diffuse large cell lymphoma (n = 5, 28%), chronic lymphocytic
      leukemia/lymphoma (n = 4, 22%), multiple myeloma (n = 2, 11%), Waldenstrom's
      macroglobulinemia (n = 2, 11%), extranodal marginal zone lymphoma (n = 2, 11%),
      plasmablastic lymphoma (n = 1, 6%), and unspecified non-Hodgkin lymphoma (n = 2,
      11%). Compared with patients with primary CL, patients with secondary CL had a
      shorter mean duration of ocular symptoms (5 vs. 17 months), had less often
      received steroids before referral (11% vs. 46%), and were more likely to have
      bilateral ocular involvement (33% vs. 20%). Eyes with secondary CL had a higher
      rate of poor vision (<=20/200) (46% vs. 12%), iris (20% vs. 4%) or ciliary body
      (30% vs. 8%) lymphoma, episcleral vascular congestion (40% vs. 16%), anterior
      chamber reaction (30% vs. 14%), hyphema (15% vs. 0%), vitreous cellular
      infiltration (30% vs. 4%), and severe media haziness (20% vs. 0%). Secondary CL
      was morphologically more high grade (50% diffuse large cell lymphoma) compared
      with primary CL (37% low-grade non-Hodgkin lymphoma, 27% extranodal marginal zone
      lymphoma). None of the 33 patients with primary CL and subsequent follow-up
      developed systemic lymphoma during a mean follow-up of 50 months (median, 35
      months; range, 2-231 months). CONCLUSIONS: Secondary CL is morphologically high
      grade and associated with more severe ocular findings. Patients with CL and no
      known systemic lymphoma at presentation should undergo systemic evaluation to
      rule out the possibility of undiagnosed concurrent systemic lymphoma. However,
      none of the patients with primary CL in our study had late development of
      systemic lymphoma.

PMID- 23978623
TI  - Evaluation of the anterior chamber angle in glaucoma: a report by the american
      academy of ophthalmology.
AB  - OBJECTIVE: To assess the published literature pertaining to the association
      between anterior segment imaging and gonioscopy and to determine whether such
      imaging aids in the diagnosis of primary angle closure (PAC). METHODS: Literature
      searches of the PubMed and Cochrane Library databases were last conducted on July
      6, 2011. The searches yielded 371 unique citations. Members of the Ophthalmic
      Technology Assessment Committee Glaucoma Panel reviewed the titles and abstracts
      of these articles and selected 134 of possible clinical significance for further
      review. The panel reviewed the full text of these articles and identified 79
      studies meeting the inclusion criteria, for which the panel methodologist
      assigned a level of evidence based on a standardized grading scheme adopted by
      the American Academy of Ophthalmology. Three, 70, and 6 studies were rated as
      providing level I, II, and III evidence, respectively. RESULTS: Quantitative and
      qualitative parameters defined from ultrasound biomicroscopy (UBM), anterior
      segment optical coherence tomography (OCT), Scheimpflug photography, and the
      scanning peripheral anterior chamber depth analyzer (SPAC) demonstrate a strong
      association with the results of gonioscopy. There is substantial variability in
      the type of information obtained from each imaging method. Imaging of structures
      posterior to the iris is possible only with UBM. Direct imaging of the anterior
      chamber angle (ACA) is possible using UBM and OCT. The ability to acquire OCT
      images in a completely dark environment allows greater sensitivity in detecting
      eyes with appositional angle closure. Noncontact imaging using OCT, Scheimpflug
      photography, or SPAC makes these methods more attractive for large-scale PAC
      screening than contact imaging using UBM. CONCLUSIONS: Although there is evidence
      suggesting that anterior segment imaging provides useful information in the
      evaluation of PAC, none of these imaging methods provides sufficient information
      about the ACA anatomy to be considered a substitute for gonioscopy. Longitudinal
      studies are needed to validate the diagnostic significance of the parameters
      measured by these instruments for prospectively identifying individuals at risk
      for PAC. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be
      found after the references.

PMID- 23978624
TI  - United Kingdom National Ophthalmology Database study of vitreoretinal surgery:
      report 3, retinal detachment.
AB  - PURPOSE: To describe rhegmatogenous retinal detachment (RD) surgery. DESIGN:
      National Ophthalmology Database study. PARTICIPANTS: A total of 3403 eyes from
      3321 patients undergoing primary RD surgery. METHODS: Participating centers
      prospectively collected clinical data using a single electronic medical record
      system, with automatic extraction of anonymized data to a national database, from
      2002 to 2010. MAIN OUTCOME MEASURES: Description of the primary procedures
      performed, intraoperative complication rate, and proportion of eyes undergoing
      subsequent RD or cataract surgery. We undertook an exploratory analysis of change
      in visual acuity (VA) using the data available. RESULTS: Of 3403 operations, 2693
      (79.1%) were pars plana vitrectomy (PPV), 413 (12.1%) were retinopexy with a
      scleral buckle (SB), and 297 (8.7%) were PPV with an SB (PPV-SB). For PPV and PPV
      SB, 18.8% were with hexafluoroethane, 12.1% were with perfluoropropane, 43.1%
      were with sulfahexafluoride, 1.8% were with air, 17.9% were with silicone oil,
      and 10.7% were with cataract surgery. Within 1 year of vitrectomy, 52.1% of
      phakic eyes had undergone cataract surgery. For all RD operations combined (and
      excluding cataract surgery complications), 5.1% had 1 or more intraoperative
      complication, 13.0% underwent further RD surgery, and 8.3% had silicone oil in
      situ at last review. The RD reoperation rate was 13.3%, 12.3%, and 14.5% for PPV,
      SB, and PPV-SB, respectively. For 961 eyes with a baseline and final VA
      measurement, the median presenting logarithm of the minimum angle of resolution
      VA improved from 1.0 to 0.5 (20/200-20/63) after a median follow-up of 0.6 years.
      CONCLUSIONS: These results may help vitreoretinal surgeons to benchmark their
      intraoperative complication rate and reoperation rate and to compare their
      surgical techniques with their peers'. They suggest that the benefits of RD
      surgery greatly outweigh the risks.

PMID- 23978625
TI  - Associations among low back pain, income, and body mass index in Taiwan.
AB  - BACKGROUND CONTEXT: There is a lack of literature on the association of obesity
      with low back pain (LBP) in oriental countries. Furthermore, no research has
      explored whether higher socioeconomic status cushions obesity-related risk of
      LBP. PURPOSE: This study aims to investigate the association between obesity and
      LBP and to investigate the effects of socioeconomic status on this association.
      STUDY DESIGN: This was a retrospective cohort study using data from Taiwan's 2001
      National Health Interview Survey and 2002 to 2004 National Health Insurance claim
      records. PATIENT SAMPLE: The sample consisted of 12,862 adults who were aged 18
      or older in 2001. OUTCOME MEASURES: Persons with at least one outpatient or
      inpatient claim record including 724 as a diagnosis code were defined as LBP
      patients. RESULTS: The estimated risk levels of being overweight (23.0<=body mass
      index [BMI]<25.0) and of being in Class I of obesity (25.0<=BMI<30.0) were the
      same (hazard ratio [HR]=1.31), and no statistically significant difference in
      risk level was detected among persons with different economic levels. Among
      people in Class II of obesity (BMI>=30.0), the LBP risk levels were different for
      persons with an economic level in the bottom quintile (defined as the poor) and
      their better-off counterparts (HR=1.77 vs. 1.24, p<.05). CONCLUSIONS: Obesity
      related risk of LBP is substantially higher for poor people than for those with
      higher socioeconomic status. Weight reduction should be promoted as a way to
      reduce LBP. Because income may serve as a proxy for other variables, the
      mechanisms underlying the empirical observed associations need to be further
      explored.

PMID- 23978626
TI  - Comparison of toxicity effects of ropivacaine, bupivacaine, and lidocaine on
      rabbit intervertebral disc cells in vitro.
AB  - BACKGROUND CONTEXT: It has been shown that bupivacaine, the most commonly used
      local anesthetic to relieve or control pain in interventional spine procedures,
      is cytotoxic to intervertebral disc (IVD) cells in vitro. However, some other
      common local anesthetics, such as ropivacaine and lidocaine, are also frequently
      used in the treatment of spine-related pain, and the potential effects of these
      agents remain unclear. PURPOSE: The purpose of this study was to evaluate the
      effect of various local anesthetics on rabbit IVD cells in vitro and further
      compare the cytotoxicity of ropivacaine, bupivacaine, lidocaine, and saline
      solution control. STUDY DESIGN: Controlled laboratory study. SUBJECTS: Rabbit
      annulus fibrosus (AF) and nucleus pulposus (NP) cells were isolated from Japanese
      white rabbits. METHODS: Both AF and NP cells at the second generation maintained
      in monolayer were exposed to various concentrations of local anesthetics (eg,
      bupivacaine) or different durations of exposure and evaluated for cell viability
      by use of cell counting kit-8 (CCK-8). In addition, to compare the cytotoxicity
      of ropivacaine, bupivacaine, lidocaine, and saline solution control in commercial
      concentration, the viability was analyzed by flow cytometry after 60-minute
      exposure, and the morphologic changes were observed by the phase-contrast
      microscopy. Apoptosis and necrosis of IVD cells were confirmed by using
      fluorescence microscopy with double staining of Hoechst 33342 and propidium
      iodide. RESULTS: Rabbit IVD cell death demonstrated a time and dose dependence in
      response to bupivacaine and lidocaine. However, ropivacaine only exerted a
      significant time-dependent effect on IVD cells. There was no significant
      difference in IVD viability after treatment with different doses of ropivacaine.
      In addition, the results showed that lidocaine was the most toxic of the three
      local anesthetics and that ropivacaine presented less cytotoxicity than lidocaine
      and bupivacaine. Fluorescence microscopy also confirmed that the short-term toxic
      effect of local anesthetics on both AF and NP cells was mainly caused by necrosis
      rather than apoptosis. CONCLUSIONS: Results show that bupivacaine and lidocaine
      decrease cell viability in rabbit IVD cells in a dose- and time-dependent manner.
      All local anesthetics should be avoided if at all possible. Ropivacaine may be a
      choice if necessary, but it is also toxic. The increase in cell death is more
      related with cell necrosis rather than cell apoptosis. If these results can be
      corroborated in tissue explant models or animal studies, caution regarding
      diagnosing, treating, and controlling spine-related pain with local anesthetics
      is prompted.

PMID- 23978627
TI  - Phylogeography in the northern Andes: complex history and cryptic diversity in a
      cloud forest frog, Pristimantis w-nigrum (Craugastoridae).
AB  - We investigated the pattern of genetic and morphological variation and the timing
      of diversification in a Neotropical direct developing frog, Pristimantis w-nigrum
      (Craugastoridae) to gain insight into the historical biogeography of the northern
      Andes. Phylogenetic inference and analyses of genetic differentiation at
      mitochondrial and nuclear markers reveal eight mitochondrial clades that display
      concordant and highly structured nuclear genetic variation along both eastern and
      western slopes of the Ecuadorian Andes. These eight phylogroups are deeply
      divergent and show little evidence of change in effective size over substantial
      periods of time. Consistent with other phylogenetic studies of vertebrates in the
      Andes, the timing of genetic divergence among lineages coincides with sequential
      bouts of Andean orogenesis during the late Miocene and early Pliocene.
      Morphometric analyses recover little morphological variation among populations in
      spite of considerable genetic divergence. The deep genetic differentiation among
      populations of P. w-nigrum suggests that this species harbors unrecognized
      diversity and may represent a complex of cryptic species. These results
      illuminate the evolutionary processes that generate diversity in tropical montane
      biomes and underscore the fact that cryptic diversity may be an important
      component of Neotropical montane biodiversity. 

PMID- 23978628
TI  - Enhanced avoidance behavior in social anxiety: evidence from a probabilistic
      learning task.
AB  - BACKGROUND AND OBJECTIVES: Social phobia is characterized by avoidance of feared
      social situations. Although avoidance is a central feature of social anxiety, few
      studies have examined avoidance learning. METHODS: We used a probabilistic
      instrumental learning paradigm where participants had to learn by trial and error
      which response led to the disappearance of a neutral or angry face. 20 high
      socially anxious and 20 non-socially anxious individuals with an average level of
      social anxiety learned to avoid an angry or a neutral face by choosing one of two
      cues. Each of the cues led to the disappearance of the face either with high or
      low reinforcement probability. RESULTS: Groups learned to choose the more
      effective cue across trials and did not differ with regard to self-report
      valence, arousal for the faces or the a posteriori estimated reinforcement
      probability for both cues. High socially anxious individuals as compared to the
      controls chose the high probability cue significantly more often and were slower
      particularly when the neutral face could be avoided. Notably, HSA engaged in more
      avoidance responding to the neutral as compared to the angry face early on during
      the experiment. LIMITATIONS: Due to the experimental design, the observed
      avoidance behavior most likely reflects the motivation for avoidance rather than
      contingency learning per se. CONCLUSIONS: In social anxiety, neutral faces might
      be processed as ambiguous social cues and strongly motivate avoidance behavior.

PMID- 23978629
TI  - Rumination prospectively predicts executive functioning impairments in
      adolescents.
AB  - BACKGROUND AND OBJECTIVES: The current study tested the resource allocation
      hypothesis, examining whether baseline rumination or depressive symptom levels
      prospectively predicted deficits in executive functioning in an adolescent
      sample. The alternative to this hypothesis was also evaluated by testing whether
      lower initial levels of executive functioning predicted increases in rumination
      or depressive symptoms at follow-up. METHODS: A community sample of 200
      adolescents (ages 12-13) completed measures of depressive symptoms, rumination,
      and executive functioning at baseline and at a follow-up session approximately 15
      months later. RESULTS: Adolescents with higher levels of baseline rumination
      displayed decreases in selective attention and attentional switching at follow
      up. Rumination did not predict changes in working memory or sustained and divided
      attention. Depressive symptoms were not found to predict significant changes in
      executive functioning scores at follow-up. Baseline executive functioning was not
      associated with change in rumination or depression over time. CONCLUSIONS:
      Findings partially support the resource allocation hypothesis that engaging in
      ruminative thoughts consumes cognitive resources that would otherwise be
      allocated towards difficult tests of executive functioning. Support was not found
      for the alternative hypothesis that lower levels of initial executive functioning
      would predict increased rumination or depressive symptoms at follow-up. Our study
      is the first to find support for the resource allocation hypothesis using a
      longitudinal design and an adolescent sample. Findings highlight the potentially
      detrimental effects of rumination on executive functioning during early
      adolescence.

PMID- 23978630
TI  - [Profound anemia, hemoglobinuria ... where to stop in the etiological
      investigation?].

PMID- 23978631
TI  - Intra-articular fate of degradable poly(ethyleneglycol)-hydrogel microspheres as
      carriers for sustained drug delivery.
AB  - A novel degradable microsphere (MS) for intra-articular drug delivery, composed
      of a polyethylene glycol (PEG) core containing degradable regions made of short
      poly-(lactic-co-glycolic acid) (PLGA) sequences - named PEG-hydrogel MS - was
      injected into the cavity of sheep shoulder joint, and compared to non-degradable
      MS devoid of hydrolysable crosslinker in terms of location, degradation and
      inflammation. One week after intra-articular injection both groups of MS were
      localized beneath the synovial lining of the synovial fringes located at bottom
      of the shoulder joint, while a fraction of particles remained in synovial fluid.
      Histological analyses made one and 4 weeks after intra-articular injection showed
      cell proliferation around the non-degradable MS entrapped within the synovium. By
      contrast, degradable PEG-hydrogel MS were surrounded by few cells. The
      degradation of degradable PEG-hydrogel MS within the synovium was slow and was
      not fully complete after four weeks. Our findings indicate that the tissue
      entrapment of MS below the synovial lining was independent of the material
      degradability, while degradable PEG-hydrogel MS are less inflammatory than the
      non-degradable one. Degradable PEG-hydrogel MS offer several advantages over the
      non-degradable MS as carriers for a sustained drug delivery in synovial tissue
      according to the low intensity of inflammatory reaction triggered in synovium. 

PMID- 23978632
TI  - Evaluation of solubility and partition properties of ampicillin-based ionic
      liquids.
AB  - In order to overcome the problems associated with low water solubility, and
      consequently low bioavailability of active pharmaceutical ingredients (APIs),
      herein we explore a modular ionic liquid synthetic strategy for improved APIs.
      Ionic liquids containing L-ampicillin as active pharmaceutical ingredient anion
      were prepared using the methodology developed in our previous work, using organic
      cations selected from substituted ammonium, phosphonium, pyridinium and
      methylimidazolium salts, with the intent of enhancing the solubility and
      bioavailability of L-ampicillin forms. In order to evaluate important properties
      of the synthesized API-ILs, the water solubility at 25  degrees C and 37  degrees
      C (body temperature) as well as octanol-water partition coefficients (Kow's) and
      HDPC micelles partition at 25  degrees C were measured. Critical micelle
      concentrations (CMC's) in water at 25  degrees C and 37  degrees C of the
      pharmaceutical ionic liquids bearing cations with surfactant properties were also
      determined from ionic conductivity measurements.

PMID- 23978633
TI  - Molecular diagnosis of eosinophilic esophagitis by gene expression profiling.
AB  - BACKGROUND & AIMS: Gene expression profiling provides an opportunity for
      definitive diagnosis but has not yet been well applied to inflammatory diseases.
      Here we describe an approach for diagnosis of an emerging form of esophagitis,
      eosinophilic esophagitis (EoE), which is currently diagnosed by histology and
      clinical symptoms. METHODS: We developed an EoE diagnostic panel (EDP) comprising
      a 96-gene quantitative polymerase chain reaction array and an associated dual
      algorithm that uses cluster analysis and dimensionality reduction using a cohort
      of randomly selected esophageal biopsy samples from pediatric patients with EoE
      (n = 15) or without EoE (non-EoE controls, n = 14) and subsequently vetted the
      EDP using a separate cohort of 194 pediatric and adult patient samples derived
      from both fresh or formalin-fixed, paraffin-embedded tissue: active EoE (n = 91),
      control (non-EoE and EoE remission, n = 57), histologically ambiguous (n = 34),
      and reflux (n = 12) samples. RESULTS: The EDP identified adult and pediatric
      patients with EoE with approximately 96% sensitivity and approximately 98%
      specificity, and distinguished patients with EoE in remission from controls, as
      well as identified patients exposed to swallowed glucorticoids. The EDP could be
      used with formalin-fixed, paraffin-embedded tissue RNA and distinguished patients
      with EoE from those with reflux esophagitis, identified by pH-impedance testing.
      Preliminary evidence showed that the EDP could identify patients likely to have
      disease relapse after treatment. CONCLUSIONS: We developed a molecular diagnostic
      test (referred to as the EDP) that identifies patients with esophagitis in a
      fast, objective, and mechanistic manner, offering an opportunity to improve
      diagnosis and treatment, and a platform approach for other inflammatory diseases.

PMID- 23978634
TI  - Identification of Salmonella Typhimurium-specific DNA aptamers developed using
      whole-cell SELEX and FACS analysis.
AB  - Conventional methods for detection of infective organisms, such as Salmonella,
      are complicated and require multiple steps, and the need for rapid detection has
      increased. Biosensors show great potential for rapid detection of pathogens. In
      turn, aptamers have great potential for biosensor assay development, given their
      small size, ease of synthesis and labeling, lack of immunogenicity, a lower cost
      of production than antibodies, and high target specificity. In this study, ssDNA
      aptamers specific to Salmonella Typhimurium were obtained by a whole bacterium
      based systematic evolution of ligands by exponential enrichment (SELEX) procedure
      and applied to probing S. Typhimurium. After 10 rounds of selection with S.
      Typhimurium as the target and Salmonella Enteritidis, Escherichia coli and
      Staphylococcus aureus as counter targets, the highly enriched oligonucleic acid
      pool was sorted using flow cytometry. In total, 12 aptamer candidates from
      different families were sequenced and grouped. Fluorescent analysis demonstrated
      that aptamer C4 had particularly high binding affinity and selectivity; this
      aptamer was then further characterized. 

PMID- 23978635
TI  - The first transformation method for the thermo-acidophilic archaeon Thermoplasma
      acidophilum.
AB  - A transformation method yielding up to 10(4) transformants per MUg circular DNA
      was developed for Thermoplasma acidophilum. The method is based on a natural DNA
      uptake process in which T. acidophilum cells keep their integrity and turn
      competent at pH 3.5 and 58 degrees C. Shuttle vector maintenance could not be
      detected, since the used Nov(R) gyraseB gene integrated into its chromosomal
      counterpart by homologous recombination.

PMID- 23978636
TI  - The temporal dynamics of first versus second language production.
AB  - In this study we explored the temporal origin of processing differences between
      first and second language production. Forty highly proficient bilinguals named
      objects of high and low lexical frequency aloud for both L1 and L2 separately
      while event-related brain potentials (ERPs) were recorded. The first
      electrophysiological differences elicited by response language occurred at the
      same early P2 peak (~140-220 ms) where we observed the onset of the lexical
      frequency effect, but only for those bilinguals who started naming in an L1
      context and afterwards switched to an L2 naming context. The bilinguals who named
      objects in the reverse direction did not display a language effect in the ERPs.
      Taken together, the data show that the L2 naming disadvantage originates during
      the onset of lexical access and seems to be driven by both representational
      strength, which is lower for L2 words, and language control demands, which are
      higher for L2 words.

PMID- 23978637
TI  - The 18th Annual Congress of the APSR.

PMID- 23978638
TI  - Risk of thyroid cancer after the Fukushima nuclear power plant accident.
AB  - The appropriateness of the initial response and countermeasures taken following
      the Fukushima nuclear power plant accident after the Great East Japan Earthquake
      on March 11, 2011 should be further examined. Implementation of a prospective
      epidemiological study on human health risks from low-dose radiation exposure and
      comprehensive health protection from radiation should be emphasized on a basis of
      the lessons learnt from the Chernobyl nuclear power plant accident. In contrast,
      the doses to a vast majority of the population in Fukushima were not high enough
      to expect to see any increase in incidence of cancer and health effects in the
      future, however, public concerns about the long-term health effects of
      radioactive environmental contamination have increased in Japan. Since May 2011,
      the Fukushima Prefecture started the Fukushima Health Management Survey Project
      with the purpose of long-term health care administration and early medical
      diagnosis/treatment for prefectural residents. In this report, risk and
      countermeasures of thyroid cancer occurrence after nuclear accidents, especially
      due to early exposure of radioactive iodine, will be focused upon to understand
      the current situation of risk of thyroid cancer in Fukushima, and the difficult
      challenges surrounding accurate estimations of low-dose and low-dose rate
      radiation exposures will be discussed. 

PMID- 23978639
TI  - Recent progress in the diagnosis and management of chronic thromboembolic
      pulmonary hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary
      hypertension caused by non-resolving thromboembolisms of the pulmonary arteries.
      In Japan, in contrast to Western countries, CTEPH is more prevalent in women. A
      Japanese multicenter study reported that a form of CTEPH unrelated to deep vein
      thrombosis is associated with HLA-B*5201, suggesting that this form of CTEPH may
      be associated with vasculopathy. CTEPH can be cured by pulmonary endarterectomy,
      provided that the thrombi are surgically accessible; thus, early diagnosis is
      important, and all patients with exertional dyspnea should be evaluated for
      pulmonary hypertension. Ventilation/perfusion scans provide an excellent non
      invasive means to distinguish CTEPH from pulmonary arterial hypertension.
      Similarly, computed tomographic pulmonary angiograms allow for the detection of
      thrombi and evaluation of pulmonary hemodynamics in a minimally invasive manner.
      Importantly, the absence of subpleural perfusion on pulmonary angiograms can
      suggest the presence of small vessel disease. Small vessel disease might be
      involved in the pathogenesis of CTEPH, and its detection is essential in
      preventing operative death. Although no modern therapies for pulmonary arterial
      hypertension have been approved for treatment of CTEPH, a recent randomized
      control trial of riociguat in patients with CTEPH demonstrated that riociguat
      significantly improved 6-min walking distance. Further investigations into
      treatments that target endothelial dysfunction and hyperproliferative CTEPH cells
      are needed. Recently, balloon pulmonary angioplasty has emerged as a promising
      treatment modality in Japan. A specialized medical team, including at least one
      expert surgeon, should make decisions regarding patients' candidacy for pulmonary
      endarterectomy and/or balloon pulmonary angioplasty. 

PMID- 23978640
TI  - Association of IL-13 gene polymorphisms with airway hyperresponsiveness in a
      Japanese adult asthmatic population.
AB  - BACKGROUND: A single nucleotide polymorphism (SNP; rs20541) in the IL-13 gene has
      been recognized as a risk factor for asthma. This SNP causes Arg to Gln (Q)
      substitution at position 110 in the mature IL-13 protein. We have recently showed
      that FEV1 in asthmatics with the Q110 variant of IL-13 declined faster, and
      progressive airway remodeling was observed in these subjects (Wynn, 2003 [1]).
      However, the effects of the IL-13 variant on airway hyperresponsiveness (AHR)
      remain to be elucidated. We analyzed the relationship between SNP rs20541 in IL
      13 and AHR in asthmatics. METHODS: We recruited 182 asthmatics who visited the
      asthma outpatient clinic at Iwate Medical University Hospital from 2006 to 2011.
      Subjects were genotyped for rs20541. Asthma severity, atopic status, age of
      asthma onset, serum IgE concentration, AHR, and pulmonary function were studied
      in these subjects. AHR was measured using the continuous methacholine inhalation
      method (Astograph; Chest; Tokyo, Japan). RESULTS: Genotyping of rs20541 revealed
      26 A/A, 77 A/G, and 79 G/G patient genotypes. The D min (U) of the 3 genotypes
      was 1.17+/-0.300 in A/A, 1.99+/-0.35 in A/G, and 2.85+/-0.39 in G/G. The D min in
      the 3 genotypes was significantly different. Spirometric data revealed that %
      FEV1 and % FEF75 were significantly different among the 3 groups of IL-13
      genotypes, whereas no significant differences were observed in therapeutic steps,
      atopic status, house dust mite sensitization, or serum IgE concentration.
      CONCLUSION: The SNP rs20541 in IL-13 was associated with AHR in Japanese adult
      asthmatics.

PMID- 23978641
TI  - Distinct features of distant metastasis and lymph node stage in lung
      adenocarcinoma patients with epidermal growth factor receptor gene mutations.
AB  - BACKGROUND: The influence of epidermal growth factor receptor (EGFR) mutation
      status on distant and lymph node metastasis is not fully understood. METHODS:
      Ninety-five consecutive patients with stage IV lung adenocarcinoma, who had been
      examined for the EGFR mutation status, were retrospectively analyzed with regard
      to numbers of distant metastasis and clinical stage of lymph node metastasis at
      the time of diagnosis. RESULTS: While EGFR mutation status did not influence the
      presence or absence of distant metastasis in the lung, brain, or liver, patients
      with EGFR mutations demonstrated a significantly greater number of metastatic
      lesions in the lung (median: 85 vs. 4, P=0.01) and the brain (11 vs. 3.5,
      P=0.04). On the other hand, patients with EGFR mutations showed a significantly
      lower lymph node staging (P<0.01). CONCLUSION: The presence of EGFR mutations in
      patients with lung adenocarcinoma correlates with lower lymph node stage and a
      greater number of metastatic lesions in the lung and brain.

PMID- 23978642
TI  - Low-dose salbutamol suppresses airway responsiveness to histamine but not
      methacholine in subjects with asthma.
AB  - BACKGROUND: Airway hyperresponsiveness is a cardinal feature of asthma. Although
      the modulation of cholinergic neuroeffector transmission may play a role in
      airway responsiveness, in vivo evidence remains scarce. It is well known that
      histamine causes bronchoconstriction partly via vagal reflex, whereas
      methacholine does not. To investigate the significance of modulating
      neuroeffector transmission, we compared the effect of low-dose salbutamol-a beta2
      adrenoceptor agonist-on airway responsiveness to histamine with that to
      methacholine. METHODS: We enrolled 12 subjects with stable asthma. After
      screening confirmed that inhalation of low-dose salbutamol (1MUg) did not change
      their basic pulmonary function, subjects underwent measurement of airway
      responsiveness to inhaled histamine and methacholine with or without pretreatment
      with low-dose salbutamol, in a randomized, crossover fashion. Airway
      responsiveness was measured by an astograph by which respiratory conductance
      (Grs) was assessed by the forced oscillation method during continuous inhalation
      of histamine or methacholine in stepwise incremental concentrations. Airway
      responsiveness was calculated as the cumulative dose of bronchoconstrictors that
      induced a decrease of 35% in Grs. RESULTS: Inhalation of 1MUg of salbutamol
      significantly attenuated airway responsiveness to histamine but not methacholine.
      This selective attenuation was observed irrespective of disease severity or
      phenotype, namely atopy or non-atopy. CONCLUSION: Low-dose salbutamol suppresses
      airway responsiveness to histamine but not methacholine in subjects with asthma.
      The present study may provide a novel insight into the bronchoprotective
      mechanism of beta2-adorenoceptor agonist in clinical settings.

PMID- 23978643
TI  - Visualized changes in respiratory resistance and reactance along a time axis in
      smokers: a cross-sectional study.
AB  - BACKGROUND: Early detection of changes in respiratory function in smokers is
      important for the prevention of chronic obstructive pulmonary disease (COPD). The
      objective of this study was to investigate any changes in the respiratory
      impedance of smokers with normal FEV1/FVC. METHODS: We assessed and compared the
      impedance components, respiratory resistance, and reactance in both the
      inspiratory and expiratory phases of nonsmokers, smokers, and COPD patients.
      RESULTS: Approximately 60% of smokers showed elevated resistance and a negative
      shift in reactance, mainly in the expiratory phase, as observed in COPD patients.
      Smokers showed an increased gap between the maximum and minimum R5 and X5 values
      (R5sub, X5sub) in comparison with nonsmokers. Furthermore, R5-R20 was
      significantly higher in smokers than in nonsmokers. The expiratory-inspiratory
      gaps in resistance and reactance were also significantly higher in smokers than
      in nonsmokers. In smokers and COPD patients, the magnitude of expiratory X5 was
      more negative than that in nonsmokers. In smokers with V.50/V.25>=3, R5-R20 was
      significantly higher than those in smokers with V.50/V.25<3. CONCLUSIONS:
      Approximately 60% of smokers were shown to exhibit apparent impedance changes
      despite having normal FEV1/FVC values. Smoking-induced early remodeling of the
      small airways may be responsible for the observed changes in airway function of
      smokers. Further studies are necessary to determine if the change in respiratory
      impedance observed in smokers is an early indicator of COPD.

PMID- 23978644
TI  - Efficacy and safety of low-dose sirolimus for treatment of
      lymphangioleiomyomatosis.
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare disease caused by
      dysregulated activation of the mammalian target of rapamycin (mTOR). Sirolimus,
      an inhibitor of mTOR, has been reported to decrease the size of angiomyolipomas
      and stabilize pulmonary function in patients with LAM. However, the optimal dose
      for the treatment of LAM remains unclear. METHODS: We conducted a retrospective,
      observational study of 15 patients with LAM who underwent sirolimus therapy for
      more than 6 months. The efficacy was evaluated by reviewing the patients'
      clinical courses, pulmonary function and chest radiologic findings before and
      after the initiation of sirolimus treatment. RESULTS: All patients had blood
      trough levels of sirolimus lower than 5ng/mL. Sirolimus treatment improved the
      annual rates of change in FVC and FEV1 in the 9 patients who were free from
      chylous effusion (FVC, -101.0 vs. +190.0mL/y, p=0.046 and FEV1, -115.4 vs.
      +127.8mL/y, p=0.015). The remaining 7 patients had chylous effusion at the start
      of sirolimus treatment; the chylothorax resolved completely within 1-5 months of
      treatment in 6 of these cases. These results resembled those of previous studies
      in which blood trough levels of sirolimus ranged from 5 to 15ng/mL. CONCLUSIONS:
      Low-dose sirolimus (trough level, 5ng/mL or less) performed as well as the higher
      doses used previously for improving pulmonary function and decreasing chylous
      effusion in patients with LAM.

PMID- 23978645
TI  - Respiratory bronchiolitis and lung carcinoma.
AB  - BACKGROUND: Cigarette smoking is the primary causative factor for lung carcinoma
      and respiratory bronchiolitis (RB), particularly RB-associated interstitial lung
      disease (RB-ILD). However, the link between lung cancer and RB/RB-ILD remains
      undefined. We examined whether pathological fibrosis lesions exist simultaneously
      in patients with lung carcinoma because the fibrous lesions could be
      precancerous. METHODS: Clinical, radiological, and pathological features were
      consecutively evaluated in 67 current smokers, 22 ex-smokers, and 35 nonsmokers
      who underwent surgical resection for lung carcinoma. The presence of interstitial
      changes was evaluated by high-resolution computed tomography (HRCT). The
      pathological examination focused on RB, RB with fibrosis, and coexistent
      interstitial changes. RESULTS: RB with fibrosis was observed in 13/67 current
      smokers with centrilobular nodular and/or patchy ground-glass opacities patterns
      or emphysema on HRCT. RB without fibrosis was observed in 12/67 current smokers
      with a centrilobular pattern, emphysema, or a normal pattern on HRCT. The
      Brinkman smoking index was significantly higher in the RB with fibrosis group
      (1278+/-133) than in the RB without fibrosis group (791+/-131). No RB
      with/without fibrosis features were noted in nonsmokers or ex-smokers. Squamous
      cell carcinoma was observed in 11/13 patients with RB with fibrosis, whereas
      adenocarcinoma was observed in 7/12 patients with RB without fibrosis.
      CONCLUSIONS: Squamous cell carcinoma located in peripheral areas was primarily
      observed in patients with RB with fibrosis, whereas adenocarcinoma was primarily
      observed in patients with RB without fibrosis. Interstitial fibrosis with RB
      caused by continuous heavy cigarette smoking may increase the risk of developing
      squamous cell carcinoma.

PMID- 23978646
TI  - Nationwide epidemiological survey of chronic hypersensitivity pneumonitis in
      Japan.
AB  - BACKGROUND: In 1999, a Japanese epidemiological survey of chronic
      hypersensitivity pneumonitis (HP) showed that summer-type HP was the most
      prevalent variant of the disease. The number of reported cases of chronic HP has
      recently been increasing, and the clinical features of the disease seem to have
      changed. We conducted another nationwide epidemiological survey of chronic HP in
      Japan to determine better estimates of the frequency and clinical features of the
      disease. METHODS: A questionnaire was sent to qualified hospitals throughout
      Japan, and data on cases of chronic HP diagnosed between 2000 and 2009 were
      collected. RESULTS: In total, 222 cases of chronic HP from 22 hospitals were
      studied. Disease subtypes included bird-related HP (n=134), summer-type HP
      (n=33), home-related HP (n=25), farmer's lung (n=4), isocyanate-induced HP (n=3),
      and other types (n=23). The median proportion of lymphocytes in bronchoalveolar
      lavage fluid was high (24.5%). The primary findings of computed tomography of the
      chest were ground-glass attenuation and interlobular septal thickening.
      Centrilobular fibrosis was the major pathological finding on examination of
      surgical lung biopsy specimens from 93 patients. The median survival time was 83
      months. CONCLUSIONS: The proportion of bird-related HP was higher than that in
      the previous epidemiological survey, and the proportions of isocyanate-induced HP
      and farmer's lung were lower. A crucial step in diagnosing chronic HP is to
      thoroughly explore the possibility of antigen exposure.

PMID- 23978647
TI  - Solitary fibrous tumor of the pleura: ultrasonographic imaging findings of 3
      cases.
AB  - Solitary fibrous tumor (SFT) of the pleura is a rare tumor of mesenchymal origin.
      Although radiographic findings of thoracic computed tomography and magnetic
      resonance imaging in the evaluation of SFTs of the pleura have been documented,
      the value of ultrasonography is uncertain. We presented the ultrasonographic
      findings of 3 pathologically proven cases of SFTs arising from the visceral
      pleura. In all the cases, thoracic ultrasonography demonstrated homogeneous,
      hypoechoic, hemicycle, extrapulmonary lesions, which showed respiratory movement
      with the adjacent lung, consistent with pedunculated tumors. Preoperative
      thoracic ultrasonography could be useful in the evaluation of patients with
      pleural tumors, especially SFTs. 

PMID- 23978648
TI  - Mucous retention cyst of temporal bone: a mimic of cholesteatoma on DW-MRI.
AB  - Non-EPI DW imaging is increasingly being used as a sensitive sequence in
      detecting cholesteatomas especially if CT findings are not confirmatory.
      Cholesteatoma appears as a hyperintense focus on DWI. We present two cases of
      mucous retention cysts in the mastoid temporal bone/middle ear cavity, which
      present as hyperintense on non-EPI DWI and potentially may mimic cholesteatomas.
      Differentiating between the two conditions is important, as surgery can be
      avoided in mucous retention cysts. We have also discussed ways to differentiate
      between these two conditions on MRI. To our knowledge, this entity is not
      reported previously. 

PMID- 23978649
TI  - Internal heavy atom effect of Au(III) and Pt(IV) on hypocrellin A for enhanced in
      vitro photodynamic therapy of cancer.
AB  - Hypocrellin A (HA), an a natural perylene quinine photosensitizers (PSs), can
      chelate with heavy metal ions, including Au(III) and Pt(IV), to form a 1:2
      complex, which exhibits enhanced (1)O2 generation quantum yield through the
      increased intersystem crossing efficiency mediated by internal heavy atom effect.
      Besides, the chelate process greatly improved the water solubility of HA.
      Comparative studies with HA and complexes have demonstrated that the heavy-atom
      effect on HA molecules enhances the efficiency of in vitro photodynamic (PDT)
      efficacy. 

PMID- 23978650
TI  - Investigation of an F-18 oxytocin receptor selective ligand via PET imaging.
AB  - The compound 1-(1-(2-(2-(2-fluoroethoxy)-4-(piperidin-4
      yloxy)phenyl)acetyl)piperidin-4-yl)-3,4-dihydroquinolin-2(1H)-one (1) was
      synthesized and positively evaluated in vitro for high potency and selectivity
      with human oxytocin receptors. The positron emitting analogue, [F-18]1, was
      synthesized and investigated in vivo via PET imaging using rat and cynomolgus
      monkey models. PET imaging studies in female Sprague-Dawley rats suggested [F
      18]1 reached the brain and accumulated in various regions of the brain, but
      washed out too rapidly for adequate quantification and localization. In vivo PET
      imaging studies in a male cynomolgus monkey suggested [F-18]1 had limited brain
      penetration while specific uptake of radioactivity significantly accumulated
      within the vasculature of the cerebral ventricles in areas representative of the
      choroid plexus. 

PMID- 23978651
TI  - Synthesis and antioxidant evaluation of (S,S)- and (R,R)-secoisolariciresinol
      diglucosides (SDGs).
AB  - Secoisolariciresinol diglucosides (SDGs) (S,S)-SDG-1 (major isomer in flaxseed)
      and (R,R)-SDG-2 (minor isomer in flaxseed) were synthesized from vanillin via
      secoisolariciresinol (6) and glucosyl donor 7 through a concise route that
      involved chromatographic separation of diastereomeric diglucoside derivatives
      (S,S)-8 and (R,R)-9. Synthetic (S,S)-SDG-1 and (R,R)-SDG-2 exhibited potent
      antioxidant properties (EC50=292.17+/-27.71 MUM and 331.94+/-21.21 MUM,
      respectively), which compared well with that of natural (S,S)-SDG-1
      (EC50=275.24+/-13.15 MUM). These values are significantly lower than those of
      ascorbic acid (EC50=1129.32+/-88.79 MUM) and alpha-tocopherol (EC50=944.62+/
      148.00 MUM). Compounds (S,S)-SDG-1 and (R,R)-SDG-2 also demonstrated powerful
      scavenging activities against hydroxyl [natural (S,S)-SDG-1: 3.68+/-0.27;
      synthetic (S,S)-SDG-1: 2.09+/-0.16; synthetic (R,R)-SDG-2: 1.96+/-0.27], peroxyl
      [natural (S,S)-SDG-1: 2.55+/-0.11; synthetic (S,S)-SDG-1: 2.20+/-0.10; synthetic
      (R,R)-SDG-2: 3.03+/-0.04] and DPPH [natural (S,S)-SDG-1: EC50=83.94+/-2.80 MUM;
      synthetic (S,S)-SDG-1: EC50=157.54+/-21.30 MUM; synthetic (R,R)-SDG-2:
      EC50=123.63+/-8.67 MUM] radicals. These results confirm previous studies with
      naturally occurring (S,S)-SDG-1 and establish both (S,S)-SDG-1 and (R,R)-SDG-2 as
      potent antioxidants and free radical scavengers for potential in vivo use.

PMID- 23978652
TI  - Selective attention to temporal features on nested time scales.
AB  - Meaningful auditory stimuli such as speech and music often vary simultaneously
      along multiple time scales. Thus, listeners must selectively attend to, and
      selectively ignore, separate but intertwined temporal features. The current study
      aimed to identify and characterize the neural network specifically involved in
      this feature-selective attention to time. We used a novel paradigm where
      listeners judged either the duration or modulation rate of auditory stimuli, and
      in which the stimulation, working memory demands, response requirements, and task
      difficulty were held constant. A first analysis identified all brain regions
      where individual brain activation patterns were correlated with individual
      behavioral performance patterns, which thus supported temporal judgments
      generically. A second analysis then isolated those brain regions that
      specifically regulated selective attention to temporal features: Neural responses
      in a bilateral fronto-parietal network including insular cortex and basal ganglia
      decreased with degree of change of the attended temporal feature. Critically,
      response patterns in these regions were inverted when the task required
      selectively ignoring this feature. The results demonstrate how the neural
      analysis of complex acoustic stimuli with multiple temporal features depends on a
      fronto-parietal network that simultaneously regulates the selective gain for
      attended and ignored temporal features. 

PMID- 23978653
TI  - Lesion-symptom mapping of self-prioritization in explicit face categorization:
      distinguishing hypo- and hyper-self-biases.
AB  - People make faster familiarity decisions for their own face compared with a
      familiar other. Lesion studies diverge on whether this self-face prioritization
      (SFP) effect is associated with functional processes isolated in the left or
      right hemispheres. To assess both decreases (hypo-) and increases (hyper-) in SFP
      after brain lesion, we asked patients with chronic deficits to perform
      familiarity judgments to images of their own face, a familiar other, or
      unfamiliar faces. Of 30 patients, 7 showed hypo- and 6 showed hyper-self-bias
      effects, comparing responses with their own faces versus responses with a
      familiar other. Hyper-self-bias correlated with reduced executive control
      function and, at a neural level, this was associated with lesions to the left
      prefrontal and superior temporal cortices. In contrast, reduced self
      prioritization was associated with damage to the right inferior temporal
      structures including the hippocampus and extending to the fusiform gyrus. In
      addition, lesions affecting fibers crossing the right temporal cortex,
      potentially disconnecting occipital-temporal from frontal regions, diminished the
      self-bias effect. The data highlight that self-prioritized face processing is
      linked to regions in the right hemisphere associated with face recognition memory
      and it also calls on executive processes in the left hemisphere that normally
      modulate self-prioritized attention. 

PMID- 23978654
TI  - Crossmodal integration enhances neural representation of task-relevant features
      in audiovisual face perception.
AB  - Previous studies have shown that audiovisual integration improves identification
      performance and enhances neural activity in heteromodal brain areas, for example,
      the posterior superior temporal sulcus/middle temporal gyrus (pSTS/MTG).
      Furthermore, it has also been demonstrated that attention plays an important role
      in crossmodal integration. In this study, we considered crossmodal integration in
      audiovisual facial perception and explored its effect on the neural
      representation of features. The audiovisual stimuli in the experiment consisted
      of facial movie clips that could be classified into 2 gender categories (male vs.
      female) or 2 emotion categories (crying vs. laughing). The visual/auditory-only
      stimuli were created from these movie clips by removing the auditory/visual
      contents. The subjects needed to make a judgment about the gender/emotion
      category for each movie clip in the audiovisual, visual-only, or auditory-only
      stimulus condition as functional magnetic resonance imaging (fMRI) signals were
      recorded. The neural representation of the gender/emotion feature was assessed
      using the decoding accuracy and the brain pattern-related reproducibility
      indices, obtained by a multivariate pattern analysis method from the fMRI data.
      In comparison to the visual-only and auditory-only stimulus conditions, we found
      that audiovisual integration enhanced the neural representation of task-relevant
      features and that feature-selective attention might play a role of modulation in
      the audiovisual integration. 

PMID- 23978655
TI  - Inhibition of conidiophore development in Aspergillus fumigatus by an Escherichia
      coli DH5alpha strain, a promising antifungal candidate against aspergillosis.
AB  - The opportunistic human pathogen Aspergillus fumigatus produces a massive number
      of asexual spores (conidia) as the primary means of dispersal, survival, genome
      protection and infection of hosts. In this report, we investigated secretory and
      cytosolic proteins of non-pathogenic bacterial species (mostly belonging to human
      microbiome) for antifungal potential against A. fumigatus, A. flavus and A.
      niger. Our preliminary results revealed that cytosolic proteins of E. coli
      DH5alpha were most active and the less toxic against various pathogenic isolates
      of A. fumigatus (the major pathogenic species), depicting a minimum inhibitory
      concentration (MIC) of 62.50 MUg/mL, 62.50 MUg/mL and 12.50 MUg/disc using
      microbroth dilution assay (MDA), percentage spore germination inhibition assay
      (PSGI) and disc diffusion assay (DDA), respectively. E. coli protein was non
      toxic against human erythrocytes at doses up to 1000 MUg/mL as compared to
      standard drug, amphotericin B which lysed 100% of erythrocytes at a concentration
      of 37.50 MUg/mL. Time kill analysis proved it to be fungicidal in a concentration
      and time-dependent manner. Scanning electron microscopic studies (SEM) were
      carried out to prevail what kind of damage it causes to A. fumigatus. SEM results
      reported that conidiophore (structures forming conidia) development was halted as
      a major consequence, reducing the number of conidiophores to insignificant values
      as well as alteration in their morphological attributes. This feature may
      contribute to the development of new prevention strategies against Aspergillus
      infections. Hyphal atrophy was also observed, evidenced by shrinking and
      flattening of hyphal walls and reduced, abrupt hyphal branching. Such actions may
      effectively reduce the invasive ability of Aspergillus as well as it can
      sterilize the fungal burden by obstructing the conidiation pathway of A.
      fumigatus. Hence, E. coli DH5alpha, being a commensal species, can lead to the
      development of antifungal molecule with novel targets in fungal metabolism, which
      will help in combating the antifungal resistance and toxicity associated with
      current therapy.

PMID- 23978656
TI  - Probing the microenvironmental conditions for induction of superficial zone
      protein expression.
AB  - OBJECTIVE: To determine the in vitro conditions which promote expression of
      superficial zone protein (SZP). METHODS: Chondrocytes from 6-month-old calves
      were expanded in monolayer culture and the expression of SZP in alginate bead and
      monolayer culture was quantified with quantitative real time-polymerase chain
      reaction (qRT-PCR) and immunostaining. The effect of oxygen tension on SZP
      expression was determined by qRT-PRC analysis of cells cultured in two dimension
      (2D) and three dimension (3D) under hypoxic (1% pO2) or normoxic (21% pO2)
      conditions. Finally, to examine the effect of cyclic tensile strain on expression
      of SZP in 2D and 3D cultures, chondrocytes encapsulated in alginate beams or
      seeded on type I collagen coated polydimethylsiloxane (PDMS) chambers were
      subjected to 5% strain at 1 Hz, 2 h/day for 4 days or 2 h at the fourth day of
      culture and mRNA levels were quantified. RESULTS: Bovine chondrocytes in
      monolayer showed a drastic decrease in SZP expression, similar in trend to the
      commonly reported downregulation of type II collagen (Col2). Chondrocytes
      embedded in alginate beads for 4 days re-expressed SZP but not Col2. SZP
      expression was higher under normoxic conditions whereas Col2 was upregulated only
      in alginate beads under hypoxic conditions. Cyclic mechanical strain showed a
      tendency to upregulate mRNA levels of SZP. CONCLUSIONS: A microenvironment
      encompassing a soft encapsulation material and 21% oxygen is sufficient for
      fibroblastic chondrocytes to re-express SZP. These results serve as a guideline
      for the design of stratified engineered articular cartilage and suggest that
      microenvironmental cues (oxygen tension level) strongly influence the pattern of
      SZP expression in vivo.

PMID- 23978657
TI  - Exceptional arsenic (III,V) removal performance of highly porous, nanostructured
      ZrO2 spheres for fixed bed reactors and the full-scale system modeling.
AB  - Highly porous, nanostructured zirconium oxide spheres were fabricated from ZrO2
      nanoparticles with the assistance of agar powder to form spheres with size at
      millimeter level followed with a heat treatment at 450  degrees C to remove agar
      network, which provided a simple, low-cost, and safe process for the synthesis of
      ZrO2 spheres. These ZrO2 spheres had a dual-pore structure, in which
      interconnected macropores were beneficial for liquid transport and the mesopores
      could largely increase their surface area (about 98 m(2)/g) for effective contact
      with arsenic species in water. These ZrO2 spheres demonstrated an even better
      arsenic removal performance on both As(III) and As(V) than ZrO2 nanoparticles,
      and could be readily applied to commonly used fixed-bed adsorption reactors in
      the industry. A short bed adsorbent test was conducted to validate the calculated
      external mass transport coefficient and the pore diffusion coefficient. The
      performance of full-scale fixed bed systems with these ZrO2 spheres as the
      adsorber was estimated by the validated pore surface diffusion modeling. With the
      empty bed contact time (EBCT) at 10 min and the initial arsenic concentration at
      30 ppb, the number of bed volumes that could be treated by these dry ZrO2 spheres
      reached ~255,000 BVs and ~271,000 BVs for As(III) and As(V), respectively, until
      the maximum contaminant level of 10 ppb was reached. These ZrO2 spheres are non
      toxic, highly stable, and resistant to acid and alkali, have a high arsenic
      adsorption capacity, and could be easily adapted for various arsenic removal
      apparatus. Thus, these ZrO2 spheres may have a promising potential for their
      application in water treatment practice.

PMID- 23978658
TI  - Web-based versus traditional paper questionnaires: a mixed-mode survey with a
      Nordic perspective.
AB  - BACKGROUND: Survey response rates have been declining over the past decade. The
      more widespread use of the Internet and Web-based technologies among potential
      health survey participants suggests that Web-based questionnaires may be an
      alternative to paper questionnaires in future epidemiological studies. OBJECTIVE:
      To compare response rates in a population of parents by using 4 different modes
      of data collection for a questionnaire survey of which 1 involved a nonmonetary
      incentive. METHODS: A random sample of 3148 parents of Danish children aged 2-17
      years were invited to participate in the Danish part of the NordChild 2011 survey
      on their children's health and welfare. NordChild was conducted in 1984 and 1996
      in collaboration with Finland, Iceland, Norway, and Sweden using mailed paper
      questionnaires only. In 2011, all countries used conventional paper versions only
      except Denmark where the parents were randomized into 4 groups: (1) 789 received
      a paper questionnaire only (paper), (2) 786 received the paper questionnaire and
      a log-in code to the Web-based questionnaire (paper/Web), (3) 787 received a log
      in code to the Web-based questionnaire (Web), and (4) 786 received log-in details
      to the Web-based questionnaire and were given an incentive consisting of a chance
      to win a tablet computer (Web/tablet). In connection with the first reminder, the
      nonresponders in the paper, paper/Web, and Web groups were also present with the
      opportunity to win a tablet computer as a means of motivation. Descriptive
      analysis was performed using chi-square tests. Odds ratios were used to estimate
      differences in response rates between the 4 modes. RESULTS: In 2011, 1704 of 3148
      (54.13%) respondents answered the Danish questionnaire. The highest response rate
      was with the paper mode (n=443, 56.2%). The other groups had similar response
      rates: paper/Web (n=422, 53.7%), Web (n=420, 53.4%), and Web/tablet (n=419,
      53.3%) modes. Compared to the paper mode, the odds for response rate in the
      paper/Web decreased by 9% (OR 0.91, 95% CI 0.74-1.10) and by 11% (OR 0.89, 95% CI
      0.73-1.09) in the Web and Web/tablet modes. The total number of responders for
      NordChild declined from 10,291 of 15,339 (67.09%) in 1984 and 10,667 of 15,254
      (69.93%) in 1996 to 7805 of 15,945 (48.95%) in 2011 with similar declines in all
      5 Nordic countries. CONCLUSIONS: Web-based questionnaires could replace
      traditional paper questionnaires with minor effects on response rates and lower
      costs. The increasing effect on the response rate on participants replying for a
      nonmonetary incentive could only be estimated within the 2 Web-based
      questionnaire modes before the first reminder. Alternative platforms to reach
      higher participation rates in population surveys should reflect the development
      of electronic devices and the ways in which the population primarily accesses the
      Internet.

PMID- 23978659
TI  - Extracts from Leonurus sibiricus L. increase insulin secretion and proliferation
      of rat INS-1E insulinoma cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Mongolian medicine (TMM) uses
      preparations from herbs as one form of medication for the treatment of a
      diversity of diseases including diabetes mellitus (DM). We evaluated the effect
      of extracts from the plant Leonurus sibiricus L. (LS), used in TMM to treat
      typical symptoms of type 2 DM, on insulin secretion, electrophysiological
      properties, intracellular calcium concentration and cell proliferation of INS-1E
      insulinoma cells under standard cell culture conditions (SCC; 11.1mM glucose).
      MATERIALS AND METHODS: Insulin secretion was measured by ELISA, electrical
      properties were assessed by whole cell patch clamping, intracellular calcium
      concentration (Cai) by Fluo-4 time lapse imaging, insulin receptor expression was
      verified by RT-PCR and cell proliferation assessed by CellTiter-Glo(r) cell
      viability assay. RESULTS: Insulin released from INS-1E cells into the culture
      medium over 24h was significantly increased in presence of 500 mg/L aqueous LS
      extract (LS OWE) as well as methanolic LS extract (LS MeOH/H2O) but not in the
      presence of the butanol-soluble extract (LS MeOH/BuOH). Acute application of LS
      OWE resulted in a depolarization of the cell membrane potential paralleled by an
      initial increase and subsequent decline and silencing of action potential
      frequency, by KATP channel inhibition, persisting depolarization and an increase
      in Cai. The electrophysiological effects were comparable to those of 100 MUM
      tolbutamide, which, however failed to elevate insulin secretion under SCC.
      Furthermore all LS extracts stimulated INS-1E cell proliferation. CONCLUSIONS:
      The finding that extracts from Leonurus sibiricus L. enhance insulin secretion
      and/or foster cell proliferation may provide possible explanations for the
      underlying therapeutic principles in the empirical use of LS-containing
      formulations in DM and DM-related disorders as applied in TMM.

PMID- 23978660
TI  - Active disturbance rejection control in steering by wire haptic systems.
AB  - This paper introduces a steering by wired haptic system based on disturbance
      rejection control techniques. High gain Generalized Proportional Integral (GPI)
      observers are considered for the estimation of tire and steering wheel dynamic
      disturbances. These disturbances are on line canceled to ensure tracking between
      the commanded steering wheel angle and the tire orientation angle. The estimated
      disturbances at the steering rack are feedback to the steering wheel to provide a
      haptic interface with the driver. The overall system behaves as a bilateral
      master-slave system. Very few sensors and minimum knowledge of the dynamic model
      are required. Experimental results are presented on a prototype platform that
      consists on: (1) half of the steering rack of a beetle VW vehicle, (2) a steering
      wheel. 

PMID- 23978661
TI  - Discrete state space modeling and control of nonlinear unknown systems.
AB  - A novel procedure for integrating neural networks (NNs) with conventional
      techniques is proposed to design industrial modeling and control systems for
      nonlinear unknown systems. In the proposed approach, a new recurrent NN with a
      special architecture is constructed to obtain discrete-time state-space
      representations of nonlinear dynamical systems. It is referred as the discrete
      state-space neural network (DSSNN). In the DSSNN, the outputs of the hidden layer
      neurons of the DSSNN represent the system's (pseudo) state. The inputs are fed to
      output neurons and the delayed outputs of the hidden layer neurons are fed to
      their inputs via adjustable weights. The discrete state space model of the actual
      system is directly obtained by training the DSSNN with the input-output data. A
      training procedure based on the back-propagation through time (BPTT) algorithm is
      developed. The Levenberg-Marquardt (LM) method with a trust region approach is
      used to update the DSSNN weights. Linear state space models enable to use well
      developed conventional analysis and design techniques. Thus, building a linear
      model of a system has primary importance in industrial applications. Thus, a
      suitable linearization procedure is proposed to derive the linear state space
      model from the nonlinear DSSNN representation. The controllability, observability
      and stability properties are examined. The state feedback controllers are
      designed with both the linear quadratic regulator (LQR) and the pole placement
      techniques. The regulator and servo control problems are both addressed. A full
      order observer is also designed to estimate the state variables. The performance
      of the proposed procedure is demonstrated by applying for both single-input
      single-output (SISO) and multiple-input multiple-output (MIMO) nonlinear control
      problems. 

PMID- 23978662
TI  - Structural studies of the O-specific polysaccharide(s) from the
      lipopolysaccharide of Azospirillum brasilense type strain Sp7.
AB  - Lipopolysaccharide was obtained by phenol-water extraction from dried bacterial
      cells of Azospirillum brasilense type strain Sp7. Mild acid hydrolysis of the
      lipopolysaccharide followed by GPC on Sephadex G-50 resulted in a polysaccharide
      mixture, which was studied by composition and methylation analyses, Smith
      degradation and (1)H and (13)C NMR spectroscopy. The following polysaccharide
      structures were established, where italics indicate a non-stoichiometric (~40%) 2
      O-methylation of l-rhamnose. 

PMID- 23978663
TI  - Synthesis of new pyrimidine-fused derivatives as potent and selective
      antidiabetic alpha-glucosidase inhibitors.
AB  - The synthesis of a set of pyrimidine-fused derivatives (L1-L8), resulting from
      the incorporation of different fragments on the pyrimidine-fused heterocycle
      (PFH) of the earlier reported alpha-glucosidase (alpha-Gls) inhibitor (C1-C5),
      allowed the discovery of new ligands with modest and selective inhibitory
      activity. The PFH core (substructure 2) was proved to play a significant role in
      their inhibitory properties. Additionally, the substituent on substructures 1 and
      3 of the heterocyclic ring was demonstrated to be important in the enzyme
      inhibitory action of the pyrimidine-fused derivatives. Moreover, these ligands
      show selective inhibitory properties for alpha-Gls over porcine pancreatic alpha
      amylase (alpha-Amy) which is important in terms of their reduced susceptibility
      for the possible development of intestinal disturbance side effects. Therefore,
      low to moderate alpha-Amy inhibition with effective alpha-Gls inhibitory action
      may offer a better therapeutic strategy. Overall, these compounds can potentially
      offer a new opportunity to develop novel antidiabetic drugs with selective
      inhibitory action against alpha-Gls. 

PMID- 23978665
TI  - Stimulus spacing effects in duration perception are larger for auditory stimuli:
      data and a model.
AB  - Models of duration bisection have focused on the effects of stimulus spacing and
      stimulus modality. However, interactions between stimulus spacing and stimulus
      modality have not been examined systematically. Two duration bisection
      experiments that address this issue are reported. Experiment 1 showed that
      stimulus spacing influenced the classification of auditory, but not visual,
      stimuli. Experiment 2 used a wider stimulus range, and showed stimulus spacing
      effects for both visual and auditory stimuli, although the effects were larger
      for auditory stimuli. A version of Temporal Range Frequency Theory was applied to
      the data, and was used to demonstrate that the qualitative pattern of results can
      be captured with the single assumption that the durations of visual stimuli are
      less discriminable from one another than are the durations of auditory stimuli. 

PMID- 23978664
TI  - Shared and distinct factors driving attention and temporal processing across
      modalities.
AB  - In addition to the classic finding that "sounds are judged longer than lights,"
      the timing of auditory stimuli is often more precise and accurate than is the
      timing of visual stimuli. In cognitive models of temporal processing, these
      modality differences are explained by positing that auditory stimuli more
      automatically capture and hold attention, more efficiently closing an attentional
      switch that allows the accumulation of pulses marking the passage of time
      (Penney, Gibbon, & Meck, 2000). However, attention is a multifaceted construct,
      and there has been little attempt to determine which aspects of attention may be
      related to modality effects. We used visual and auditory versions of the
      Continuous Temporal Expectancy Task (CTET; O'Connell et al., 2009) a timing task
      previously linked to behavioral and electrophysiological measures of mind
      wandering and attention lapses, and tested participants with or without the
      presence of a video distractor. Performance in the auditory condition was
      generally superior to that in the visual condition, replicating standard results
      in the timing literature. The auditory modality was also less affected by
      declines in sustained attention indexed by declines in performance over time. In
      contrast, distraction had an equivalent impact on performance in the two
      modalities. Analysis of individual differences in performance revealed further
      differences between the two modalities: Poor performance in the auditory
      condition was primarily related to boredom whereas poor performance in the visual
      condition was primarily related to distractibility. These results suggest that:
      1) challenges to different aspects of attention reveal both modality-specific and
      nonspecific effects on temporal processing, and 2) different factors drive
      individual differences when testing across modalities. 

PMID- 23978666
TI  - Brief report: depression and history of suicide attempts in adults with new-onset
      Type 2 Diabetes.
AB  - AIM: To assess past suicide attempts in a cohort of adults with Type 2 Diabetes
      diagnosed within the prior 24 months. METHODS: Outpatients were recruited from
      diabetes education classes or diabetes shared medical appointment. Participants
      aged 18 or over with a self-reported diagnosis of Type 2 Diabetes (T2DM) in the
      prior 24 months completed questionnaires about medical (including diabetes),
      psychiatric, and social history. Participants also completed two screening
      questionnaires for depression: Patient Health Questionnaire 9 and the
      Questionnaire Inventory for Depressive Symptoms-Self Report. Those who screened
      positive for depression had confirmatory testing with a clinician administered
      Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) checklist.
      RESULTS: In this convenience sample of 145 patients with Type 2 Diabetes, 9.7% of
      patients had history of a suicide attempt and 38.2% met diagnosis for major
      depressive disorder (MDD). Patients with MDD were more likely to have a history
      of suicide attempts than those without MDD (p=0.0002). Of the patients with prior
      suicide attempts, 50% screened positive for MDD at the time of the survey.
      CONCLUSION: In patients with newly-diagnosed Type 2 Diabetes the rate of past
      suicide attempts was nearly 10%, which is twice the rate seen in the general
      population. The rate of past suicide attempts in currently depressed patients
      with diabetes is 21.8%. These findings suggest the need for monitoring patients
      with diabetes and depression for future suicide risk.

PMID- 23978667
TI  - Molecular characterization of hepatitis E virus ORF1 gene supports a papain-like
      cysteine protease (PCP)-domain activity.
AB  - Hepatitis E Virus (HEV) ORF1 encodes the nonstructural polyprotein wherein a role
      of PCP-domain in ORF1 proteolysis and/or RNA replication still remains contested.
      A series of ORF1 mutants of HEV-SAR55 replicon were constructed and tested for
      viability in S10-3 cells. Six of PCP-'cysteine' (C457A, C459A, C471A, C472A,
      C481A and C483A) and three 'histidine' (H443L, H497L and H590L) mutants were
      lethal. Further, a highly conserved 'glycine-triad' (G815-G816-G817) in
      downstream X-domain, homologous to rubella virus protease-substrate (G1299-G1300
      G1301) was identified where two of X-mutants (G816V and G817V) turned lethal.
      However, all ORF1 sequential nucleotide-mutants conserving the amino acids were
      viable, which clearly showed post-translational regulation of HEV replication by
      PCP- and X-domains. Moreover, while vector-expressed ORF1-fusion polyprotein
      yielded a ~191 kDa band in vitro, it produced ~78 and ~35 kDa fragments ex vivo.
      Collectively, the indispensability and functional effects of 'PCP-catalytic' and
      'X-substrate' residues on HEV replication strongly supported a viral protease.

PMID- 23978668
TI  - Recurrent severe arthralgia.

PMID- 23978669
TI  - The zoonotic, fish-borne liver flukes Clonorchis sinensis, Opisthorchis felineus
      and Opisthorchis viverrini.
AB  - Clonorchis sinensis, Opisthorchis felineus and Opisthorchis viverrini are the
      three most important liver flukes involved in human health, infecting more than
      45 million people worldwide. Both C. sinensis and O. viverrini, and possibly O.
      felineus, can induce human cholangiocarcinoma as well as inducing other
      hepatobiliary pathology. Although the life cycles of all three species are
      similar, only that of O. felineus in Europe remains predominantly zoonotic, while
      O. felineus in Asia and C. sinensis have a stronger mixture of zoonotic and
      anthroponotic components in their life cycles. Opisthorchis viverrini from the
      Mekong area of southeastern Asia is predominantly anthroponotic. Here we discuss
      the comparative epidemiology of these three taxa comparing in detail the use of
      first, second and final animal hosts, and consider the potential role of humans
      in spreading these pathogens. In addition we discuss the genetic structure of all
      three species in relation to potentially cryptic species complexes. 

PMID- 23978670
TI  - Automated landmarking and labeling of fully and partially scanned spinal columns
      in CT images.
AB  - The spinal column is one of the most distinguishable structures in CT scans of
      the superior part of the human body. It is not necessary to segment the spinal
      column in order to use it as a frame of reference. It is sufficient to place
      landmarks and the appropriate anatomical labels at intervertebral disks and
      vertebrae. In this paper, we present an automated system for landmarking and
      labeling spinal columns in 3D CT datasets. We designed this framework with two
      goals in mind. First, we relaxed input data requirements found in the literature,
      and we label both full and partial spine scans. Secondly, we intended to fulfill
      the performance requirement for daily clinical use and developed a high
      throughput system capable of processing thousands of slices in just a few
      minutes. To accomplish the aforementioned goals, we encoded structural knowledge
      from training data in probabilistic boosting trees and used it to detect
      efficiently the spinal canal, intervertebral disks, and three reference regions
      responsible for initializing the landmarking and labeling. Final landmarks and
      labels are selected by Markov Random Field-based matches of newly introduced 3
      disk models. The framework has been tested on 36 CT images having at least one of
      the regions around the thoracic first ribs, the thoracic twelfth ribs, or the
      sacrum. In an average time of 2 min, we achieved a correct labeling in 35 cases
      with precision of 99.0% and recall of 97.2%. Additionally, we present results
      assuming none of the three reference regions could be detected.

PMID- 23978671
TI  - Rare earth elements (REEs): effects on germination and growth of selected crop
      and native plant species.
AB  - The phytotoxicity of rare earth elements (REEs) is still poorly understood. The
      exposure-response relationships of three native Canadian plant species (common
      milkweed, Asclepias syriaca L., showy ticktrefoil, Desmodium canadense (L.) DC.
      and switchgrass, Panicum virgatum L.) and two commonly used crop species (radish,
      Raphanus sativus L., and tomato, Solanum lycopersicum L.) to the REEs lanthanum
      (La), yttrium (Y) and cerium (Ce) were tested. In separate experiments, seven to
      eight doses of each element were added to the soil prior to sowing seeds. Effects
      of REE dose on germination were established through measures of total percent
      germination and speed of germination; effects on growth were established through
      determination of above ground biomass. Ce was also tested at two pH levels and
      plant tissue analysis was conducted on pooled samples. Effects on germination
      were mostly observed with Ce at low pH. However, effects on growth were more
      pronounced, with detectable inhibition concentrations causing 10% and 25%
      reductions in biomass for the two native forb species (A. syriaca and D.
      canadense) with all REEs and on all species tested with Ce in both soil pH
      treatments. Concentration of Ce in aboveground biomass was lower than root Ce
      content, and followed the dose-response trend. From values measured in natural
      soils around the world, our results continue to support the notion that REEs are
      of limited toxicity and not considered extremely hazardous to the environment.
      However, in areas where REE contamination is likely, the slow accumulation of
      these elements in the environment could become problematic. 

PMID- 23978672
TI  - Levels of PCDD/Fs, PCBs and PBDEs in breast milk of women living in the vicinity
      of a hazardous waste incinerator: assessment of the temporal trend.
AB  - The concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers
      (PBDEs) were determined in breast milk from women living in the vicinity of a
      hazardous waste incinerator (HWI) in Catalonia, Spain. The results were compared
      with the levels obtained in previous surveys carried out in the same area in 1998
      (baseline study), 2002 and 2007. The current total concentrations of 2,3,7,8
      chlorinated PCDD/Fs in breast milk ranged from 18 to 126 pg g(-1)fat (1.1-12. 3
      pg WHO2005-TEQPCDD/F), while the total levels of PCBs ranged from 27 to 405 pg g(
      1)fat(0.7-5.3 pg WHO2005-TEQPCB). In turn, PBDE concentrations (sum of 15
      congeners) ranged 0.3-5.1 g g(-1)fat, with a mean value of 1.3 ng g(-1)fat. A
      general decrease in the concentrations for PCDD/Fs, both planar and total PCBs,
      and PBDEs in breast milk was observed. The levels of PCDD/Fs, PCBs, and PBDEs in
      milk of women living in urban zones were higher than those corresponding to
      industrial zones (41%, 26%, and 8%, respectively). For PCDD/Fs and PCBs, the
      current decreases are in accordance with the reduction in the dietary intake of
      these pollutants that we have also observed in recent studies carried out in the
      same area of study.

PMID- 23978673
TI  - Seasonal variation and controlling factors of anaerobic ammonium oxidation in
      freshwater river sediments in the Taihu Lake region of China.
AB  - Anaerobic ammonium oxidation (anammox) has been recently recognized as an
      important pathway for the removal of fixed nitrogen (N) from aquatic systems.
      However, the functions of anammox in freshwater river systems remain uncertain.
      In this study, we evaluated the occurrence of anammox activity in two rivers in
      the Taihu Lake region in China during a seasonal survey. Homogenized sediments
      were incubated with (15)N-labeled NO3(-) and NH4(+) amendments to determine the
      potential importance of the anammox process relative to canonical
      denitrification. Production of (29)N2 and (30)N2 in slurries was determined using
      membrane inlet mass spectrometry. Potential anammox rates in the two river
      sediments ranged from 0.11+/-0.07 to 6.79+/-1.28 MUmol N m(-2) h(-1) and the
      remove of N by anammox accounted for 0.8+/-0.00% to 10.7+/-0.03% of total N2
      production. Potential anammox rates varied spatially and temporally in the two
      rivers, with the highest and lowest mean anammox rates appearing during summer
      and early autumn and during winter, respectively. The variation of the percentage
      of anammox to total N2 production displayed the same trend with potential anammox
      rates. Water temperature and NO3(-) content in sediments were the main factors
      affecting anammox activity. Anammox bacteria were detected in sediment samples
      using barcode pyrosequencing. The 16S rRNA anammox gene sequences in the river
      sediments were affiliated with Candidatus Kuenenia, Candidatus Jettenia, and
      Candidatus Scalindua, among which C. Kuenenia dominated the anammox bacterial
      communities. Our results confirmed the presence of anammox bacteria but their
      role is relatively small in removing fixed N from freshwater river systems.

PMID- 23978674
TI  - [Radiation oncology in Quebec].

PMID- 23978675
TI  - New insights into polyurethane biodegradation and realistic prospects for the
      development of a sustainable waste recycling process.
AB  - Polyurethanes are polymeric plastics that were first used as substitutes for
      traditional polymers suspected to release volatile organic hazardous substances.
      The limitless conformations and formulations of polyurethanes enabled their use
      in a wide variety of applications. Because approximately 10 Mt of polyurethanes
      is produced each year, environmental concern over their considerable contribution
      to landfill waste accumulation appeared in the 1990s. To date, no recycling
      processes allow for the efficient reuse of polyurethane waste due to their high
      resistance to (a)biotic disturbances. To find alternatives to systematic
      accumulation or incineration of polyurethanes, a bibliographic analysis was
      performed on major scientific advances in the polyurethane (bio)degradation field
      to identify opportunities for the development of new technologies to recondition
      this material. Until polymers exhibiting oxo- or hydro-biodegradative traits are
      generated, conventional polyurethanes that are known to be only slightly
      biodegradable are of great concern. The research focused on polyurethane
      biodegradation highlights recent attempts to reprocess conventional industrial
      polyurethanes via microbial or enzymatic degradation. This review describes
      several wonderful opportunities for the establishment of new processes for
      polyurethane recycling. Meeting these new challenges could lead to the
      development of sustainable management processes involving polymer recycling or
      reuse as environmentally safe options for industries. The ability to upgrade
      polyurethane wastes to chemical compounds with a higher added value would be
      especially attractive.

PMID- 23978676
TI  - Cell detachment: post-isolation challenges.
AB  - Rare cells already have become established indicators for disease diagnosis, to
      help track prognosis, and in developing personalized therapy. Numerous techniques
      have been developed to effectively and specifically detect and sort rare cells
      and cell isolation techniques have gained much attention among researchers in the
      last few decades. Recent developments in nanotechnologies and microfluidics have
      been used with great promise towards these goals. The research emphasis has also
      shifted from simple detection with microfluidic devices to comprehensive
      isolation, collection and subsequent analysis with integrated and automated
      systems. The first challenge in post-isolation analysis is cell detachment from
      substrates, while keeping cells viable and unperturbed. In this review, various
      methods used for cell detachments are discussed. For effective cell sorting, the
      detachment is identified as critical criteria for selecting substrates and
      methods. 

PMID- 23978677
TI  - Right atrial and ventricular adaptations to training in male Caucasian athletes:
      an echocardiographic study.
AB  - BACKGROUND: The aim of this study was to investigate the systolic and diastolic
      properties of the right cardiac chambers (the right ventricle and right atrium)
      among different subsets of athletes to unveil potential variations in right
      ventricular and right atrial remodeling secondary to different training modes.
      METHODS: A cohort of Caucasian male top-level athletes (n = 108; 80 endurance
      athletes [EAs], mean age, 31.2 +/- 10.4 years; 28 strength-trained athletes
      [SAs], mean age, 27.4 +/- 5.7 years) and untrained controls (n = 26; mean age,
      26.6 +/- 5.6 years) (P = .327) were prospectively enrolled. Conventional
      echocardiographic parameters, including transtricuspid inflow, Doppler tissue
      imaging, and two-dimensionally derived peak systolic longitudinal strain and
      strain rate indices of the right ventricle and right atrium, were calculated.
      RESULTS: EAs had greater internal right ventricular and right atrial dimensions
      compared with SAs and controls. There were no significant differences concerning
      strain between groups (-23.1 +/- 3.7% in EAs vs -25.1 +/- 3.2% in SAs vs -23.1 +/
      3.5% in controls, P = .052), with SAs presenting higher global systolic strain
      rates (-1.42 +/- 0.22 sec(-1) in SAs vs -1.21 +/- 0.21 sec(-1) in EAs vs -1.2 +/-
      0.28 sec(-1) in controls, P = .016), as well as greater right atrial strain rate
      systolic and diastolic components. Training volume (highly vs moderately trained
      athletes) did not significantly influence deformation parameters. No significant
      differences concerning diastolic transtricuspid inflow and Doppler tissue imaging
      indices were also noted among different athlete groups and controls. CONCLUSIONS:
      Despite the existence of right geometric alterations in athletes participating in
      different sport disciplines, few meaningful differences in deformation and
      diastolic function exist.

PMID- 23978679
TI  - Histone deacetylase inhibitors suppress CXCR4-mediated dendritic cell migration
      by regulation of maturation process.
AB  - Once activated by an infected pathogen, dendritic cells (DC's) migrate toward
      secondary lymphoid organs, and release inflammatory mediators. Therefore, in some
      case, mature DC's (mDC's) are considered to be potent inflammatory inducers. In
      this study we demonstrated that histone acetylation plays an important regulatory
      role in conserving the migration activity of the DC's. We showed that histone
      deacetylase (HDAC) inhibition reduces CXC chemokine receptor 4 (CXCR4)-dependent
      DC's migration. These inhibitory effects were found to be caused by a reduction
      in the expression of CXCR4, and by the phosphorylation of p38 mitogen-activated
      protein kinase (MAPK), extracellular signal-regulated kinases 1 and 2 (ERK 1/2),
      and c-Jun N-terminal kinase (JNK). Taken together, histone deacetylase inhibitors
      (HDACi's) inhibit the phosphorylation of MAP kinases, and this inhibition reduces
      the expression of CXCR4, and this reduction decreases the chemotactic activity of
      mDC's. 

PMID- 23978678
TI  - Regulatory potential of COUP-TFs in development: stem/progenitor cells.
AB  - The formation of complex organisms is highly dependent on the differentiation of
      specialized mature cells from common stem/progenitor cells. The orphan nuclear
      receptors chicken ovalbumin upstream promoter transcription factors (COUP-TFs)
      are broadly, but not ubiquitously, expressed in multiple tissues throughout
      embryonic development and COUP-TFs are indispensible for proper organogenesis.
      Recently, growing evidence suggests a critical role of COUP-TFs in multiple
      aspects of stem/progenitor cell biology. In this review, we highlight the
      progress of COUP-TFs function and its underlying mechanism in driving
      stem/progenitor cell self-renewal, lineage specification, differentiation,
      maintenance, and cell identity in diverse tissue types. These studies provide
      novel insights into future clinical utilities of COUP-TFs in stem cell based
      therapies and in the management of diseases. 

PMID- 23978680
TI  - Accumulation of invariant NKT cells into inflamed skin in a novel murine model of
      nickel allergy.
AB  - Nickel (Ni) can cause delayed-type hypersensitivity reactions, which are thought
      to be mediated by the accumulation of T cells into inflamed skin. Accumulated T
      cells at the developmental stages in metal allergy are poorly characterized
      because a suitable animal model has not been established. To investigate the
      accumulated T cells in allergic inflamed skin, we generated a novel murine model
      of Ni-induced allergy. The murine model of Ni allergy was induced by two
      sensitizations of Ni plus lipopolysaccharide solution into the groin followed by
      three challenges with Ni solution into the footpad. Here we show that a specific
      TCR repertoire bearing Valpha14Jalpha18, called natural killer (NK) T cells, was
      expanded monoclonally in BALB/c or C57BL/6 mice. Accumulation of NKT cells was
      characterized as CD4(+) or CD4(-)CD8(-) T cells. These results suggested that NKT
      cells are major pathogenic T cells at the elicitation phase of Ni allergy. 

PMID- 23978681
TI  - A mass screening survey of cystic echinococcosis by ultrasonography, Western
      blotting, and ELISA among university students in Manisa, Turkey.
AB  - Cystic echinococcosis (CE) is one of the most important zoonotic diseases in a
      wide geographic area, including Turkey. In the present project, a total of 4275
      students from Celal Bayar University, Manisa, Turkey, were screened by
      ultrasonography (US) and specific antibodies for CE were examined by Western
      blotting (WB) and ELISA in finger prick blood samples of 2034 of 4275 volunteered
      students. We aimed to report the apparent prevalence of CE based on different
      diagnostic procedures and to compare WB and ELISA with US in diagnosis of CE in a
      mass screening setting. Six new cases were diagnosed as CE by US during the
      survey. In addition to these cases, three students were also detected to have
      been previously operated and pathologically confirmed for hepatic CE. US revealed
      parenchymal changes in these cases in concordance with their operation history;
      so, the prevalence of CE by US was calculated as 0.21% (9/4275) (95%CI, 0.11
      0.39%) among university students in Manisa. Bands were detected at 8, 28, 32, 38,
      42, 47, 70 and 90kDa by WB and the cases were considered to be positive for CE
      when at least three of the bands were seen together. Apparent prevalence of CE by
      ELISA and WB were found to be 2.11% (43/2034) (95%CI, 1.57-2.83%) and 0.25%
      (5/2034) (95%CI, 0.10-0.57%), respectively. Of the six US positive cases, WB was
      positive in only one case with two cysts in the liver. All of four cases with
      liver involvement were positive by ELISA. The high prevalence of CE among
      university students in Manisa indicated that CE is a major health problem in this
      area of Turkey. Our results supported that WB is rather difficult and not
      feasible as a mass screening test and may not be effective for confirmation
      especially in asymptomatic cases. As a result, we recommend US to be used
      initially in mass screening surveys for CE followed by confirmation by ELISA for
      suspected cases. Further examination primarily by chest X-ray followed by
      computed tomography and/or magnetic resonance imaging, if needed, should be
      recommended for US negative, ELISA and WB positive individuals who may have non
      abdominal cysts. 

PMID- 23978683
TI  - Transcutaneous immunization using microneedles and cubosomes: Mechanistic
      investigations using Optical Coherence Tomography and Two-Photon Microscopy.
AB  - Transcutaneous (TCI) immunization is a novel vaccination approach that provides
      many advantages over traditional parenteral vaccination. However, a major barrier
      to TCI is mediating penetration of vaccine antigens through the stratum corneum
      (SC) to the deeper tissue layers. Many approaches have been investigated for
      enhancing drug penetration into the skin including microneedles (MNs) to
      transiently breach the SC barrier and incorporation of vaccines into penetration
      enhancing delivery systems. This study utilized MNs and a lipid-based colloidal
      delivery system (cubosomes) as a synergistic approach for the delivery of
      vaccines through the skin. The penetration and permeation of the peptide antigen
      into and through skin were analysed quantitatively and qualitatively using
      techniques including Optical Coherence Tomography and two-photon microscopy. It
      was found that while the use of MNs increased the permeation of an aqueous
      peptide mixture through skin, cubosome-formulated peptide and cubosomes were
      retained in the skin. Therefore, it is proposed that a combined approach using
      MNs and cubosomes will be an efficient system for the local delivery of antigen
      to immunocompetent cells in the skin. 

PMID- 23978682
TI  - Incorporation of histone derived recombinant protein for enhanced disassembly of
      core-membrane structured liposomal nanoparticles for efficient siRNA delivery.
AB  - A novel recombinant protein tetra-H2A (TH) derived from histone H2A has been
      developed to replace protamine as a conditionally reversible, nucleic acid
      condensing agent. The novel protein will address the insufficient release of
      nucleic acid therapeutics, which is captured by protamine for siRNA delivery. TH
      is composed of 4 tandem repeats of the histone H2A N-terminal sequence,
      intervened by the cathepsin D cleavage site. The repeating H2A sequence enhances
      the binding affinity to anionic nucleic acids, forming more stable condensates,
      as demonstrated by the binding affinity assay. The TH/siRNA condensates are
      formulated into a core-membrane structured liposomal nanoparticle (NP). The
      endosomes of cancer cells are rich in cathepsin D, allowing on-site degradation
      of TH and facilitating the intracellular release of siRNA. The NPs assembled with
      TH produced a higher silencing efficiency of target genes in vitro and in vivo
      than the NPs assembled with protamine as the nucleic acid condensing agent. The
      exploitation of TH in the NP formulation exhibited a biocompatibility profile
      similar to that of protamine, with minimal immunostimulating and systemic
      toxicity observed after repeated administration. 

PMID- 23978684
TI  - High rate of suicide attempt and associated psychological traits in an isolated
      tribal population of North-East India.
AB  - BACKGROUND: Cases of suicide documented earlier all over the world reflect the
      presence of suicide behavior in primitive world at a higher rate compared to
      general urban population. The cause of such behavior is thought to be different
      among tribes and mental health was rarely presumed to be associated. In India,
      several ethnographic narratives described instances of suicides among several
      tribes, but evaluation of psychological traits were lacking. The present study on
      Idu Mishmi is an attempt to further validate earlier report of high rate of
      suicides among them and to evaluate psychological traits. METHODS: Interview and
      administration of Patient Health Questionnaire (PHQ) on 218 individuals comprised
      the data. Bi-variate analyses and linear multiple regression were done to
      evaluate psychological traits in suicide behavior. RESULTS: In the Idu Mishmi
      Population suicide attempt (14.22%) was higher than urban population in general
      (0.4-4.2%) and females were at higher risk. Depression (8.26%) was comparable
      with earlier reports, whereas anxiety syndrome (6.42%), alcohol abuse (36.24%)
      and eating disorder like Binge eating (6.42%), Bulimia nervosa (1.38%) were also
      recorded in the population. LIMITATIONS: Absence of psychiatry clinic and
      mechanism of recording suicide occurrences in remote tribal area is the basic
      limitation of the study. CONCLUSION: Depression and gender turned out to be
      significant determinants of suicide attempt in the studied population, whereas
      alcohol abuse was not a significant factor.

PMID- 23978686
TI  - Breastfeeding: best for babies.

PMID- 23978685
TI  - The structure of emotional symptoms in the postpartum period: is it unique?
AB  - BACKGROUND: In perinatal mental health there is a lack of consensus as to whether
      postpartum emotional disorders are unique in their aetiology and clinical
      presentation. If the clinical presentation is unique, then the factor structure
      should be different in a postpartum sample. METHODS: Admission and discharge
      scores on the Depression Anxiety Stress Scales (DASS; Lovibond and Lovibond,
      1995b) scores were collected for 527 inpatients admitted to a Psychiatric Mother
      and Baby Unit. Reliability and validity of the DASS were examined, and
      confirmatory factor analysis evaluated the fit of a series of models of the DASS.
      RESULTS: The DASS had sound reliability and validity in the postpartum inpatient
      sample. The optimal fitting factor solution for the DASS was a revised three
      factor model previously supported in studies of other clinical and non-clinical
      populations. The factor structure was invariant across admission and discharge.
      LIMITATIONS: The sample consisted of postpartum inpatients and the
      generalisability of results to other postpartum samples is not known.
      CONCLUSIONS: Postpartum emotional symptoms have the same factor structure
      previously observed in non-postpartum populations, consistent with the hypothesis
      that postpartum emotional disorders are similar to those occurring at other
      times. The present study provides support for the reliability and validity of the
      DASS in the postpartum period.

PMID- 23978687
TI  - Effects of antennule morphology and flicking kinematics on flow and odor sampling
      by the freshwater crayfish, Procambarus clarkii.
AB  - The flow structure around the lateral antennular flagellum of the freshwater
      crayfish, Procambarus clarkii, was quantified to determine how antennule
      morphology and flicking kinematics affect fine-scale flow surrounding their
      chemosensory sensilla, called aesthetascs. Particle image velocimetry was used to
      measure velocity and vorticity of flow between aesthetascs of dynamically scaled
      physical models of P. clarkii antennules. Results revealed that the spacing
      between aesthetascs and antennule flicking speed induces substantial changes in
      fluid flow near aesthetascs. The downstroke flicking motion of the antennule
      occurs at a peak speed of 2.7cm/s. The returnstroke occurs at approximately 70%
      of this speed, but the fluid velocity between aesthetascs during the returnstroke
      is approximately 15% compared with the downstroke. The significant decrease in
      fluid flow near aesthetascs results from the reduced antennule speed and from the
      coupled interaction of boundary layers of the aesthetascs and antennule during
      the returnstroke. Odorant-laden fluid captured during the downstroke is retained
      between the aesthetascs during the slower returnstroke, and sufficient time
      occurs for odorant molecules to molecularly diffuse to aesthetasc surfaces. In
      addition, locally generated vorticity was observed near the tip of the
      aesthetascs, which may induce odorant transport to aesthetasc surfaces and
      enhance olfactory response times to odors. 

PMID- 23978688
TI  - Differential effects of electrical stimulation of the central amygdala and
      lateral hypothalamus on fos-immunoreactive neurons in the gustatory brainstem and
      taste reactivity behaviors in conscious rats.
AB  - Projections from the central amygdala (CeA) and lateral hypothalamus (LH)
      modulate the activity of gustatory brainstem neurons, however, the role of these
      projections in gustatory behaviors is unclear. The goal of the current study was
      to determine the effects of electrical stimulation of the CeA or LH on
      unconditioned taste reactivity (TR) behaviors in response to intra-oral infusion
      of tastants. In conscious rats, electrical stimulation of the CeA or LH was
      delivered with and without simultaneous intra-oral infusion of taste solutions
      via an intra-oral cannula. Immunohistochemistry for the Fos protein was used to
      identify neurons in the gustatory brainstem activated by the electrical and/or
      intra-oral stimulation. In the absence of intra-oral infusion of a tastant,
      electrical stimulation of either the CeA or the LH increased the number of
      ingestive, but not aversive, TR behaviors performed. During intra-oral infusions
      of taste solutions, CeA stimulation tended to increase aversive behaviors whereas
      LH stimulation dramatically reduced the number of aversive responses to quinine
      hydrochloride (QHCl). These data indicate that projections from the CeA and LH
      alter TR behaviors. A few of the behavioral effects were accompanied by changes
      in the number of Fos-immunoreactive neurons in the gustatory brainstem,
      suggesting a possible anatomical substrate for these effects. 

PMID- 23978689
TI  - A new hypothesis on the manifestation of cerebral malaria: the secret is in the
      liver.
AB  - Despite the abundance of information on cerebral malaria (CM), the pathogenesis
      of this disease is not completely understood. At present, two nonexclusive
      dominant hypotheses exist to explain how the neurological syndrome manifests: the
      sequestration (or mechanical) hypothesis and the inflammatory hypothesis. The
      sequestration hypothesis states that sequestration of Plasmodium falciparum
      parasitized red blood cells (pRBCs) to brain capillary endothelia causes
      obstruction of capillary blood flow followed by brain tissue anoxia and coma. The
      inflammatory hypothesis postulates that P. falciparum infection releases toxic
      molecules in the circulation, inducing an imbalanced systemic inflammatory
      response that leads to coagulopathy, brain endothelial cell dysfunction,
      accumulation of leukocytes in the brain microcirculation, blood brain barrier
      (BBB) leakage, cerebral vasoconstriction, edema, and coma. However, both
      hypotheses, even when considered together, are not sufficient to fully explain
      the pathogenesis of CM. Here, we propose that the development of acute liver
      failure (ALF) together with BBB breakdown are the necessary and sufficient
      conditions for the genesis of CM. ALF is characterized by coagulopathy and
      hepatic encephalopathy (HE) in a patient without pre-existing liver disease.
      Signs of hepatic dysfunction have been shown to occur in 2.5-40% of CM patients.
      In addition, recent studies with murine models demonstrated that mice presenting
      experimental cerebral malaria (ECM) had hepatic damage and brain metabolic
      changes characteristic of HE. However, the occurrence of CM in patients with mild
      or without apparent hepatocellular liver damage and the presence of liver damage
      in non-CM murine models indicate that the development of ALF during malaria
      infection is not the single factor responsible for neuropathology. To solve this
      problem, we also propose that BBB breakdown contributes to the pathogenesis of CM
      and synergizes with hepatic failure to cause neurological signs and symptoms. BBB
      dysfunction would thus occur in CM by a mechanism similar to the one occurring in
      sepsis and is in agreement with the inflammatory hypothesis. Nevertheless,
      differently from in the inflammatory hypothesis, BBB leakage would facilitate the
      penetration of ammonia and other toxins into the brain parenchyma, but would not
      be sufficient to cause CM when occurring alone. We believe our hypothesis better
      explains the pathogenesis of CM, does not have problems to deal with the
      exception data not explained by the previous hypotheses, and reveals new targets
      for adjunctive therapy. 

PMID- 23978690
TI  - Low-intensity self-management intervention for persons with type 2 diabetes using
      a mobile phone-based diabetes diary, with and without health counseling and
      motivational interviewing: protocol for a randomized controlled trial.
AB  - BACKGROUND: The present study protocol is designed to cover the Norwegian part of
      the European Union Collaborative Project-REgioNs of Europe WorkINg together for
      HEALTH (RENEWING HEALTH). Self-management support is an important element of care
      for persons with type 2 diabetes (T2D) for achieving metabolic control and
      positive lifestyle changes. Telemedicine (TM) with or without health counseling
      may become an important technological aid for self-management and may provide a
      user-centered model of care. In spite of many earlier studies on TM, there
      remains a lack of consensus in research findings about the effect of TM
      interventions. OBJECTIVE: The aim of RENEWING HEALTH is to validate and evaluate
      innovative TM tools on a large scale through a common evaluation, making it
      easier for decision makers to choose the most efficient and cost-effective
      technological interventions. The Norwegian pilot study evaluates whether the
      introduction of a mobile phone with a diabetes diary application together with
      health counseling intervention produces benefits in terms of the desired
      outcomes, as reflected in the hemoglobin A1c level, health-related quality of
      life, behavior change, and cost-effectiveness. METHODS: The present study has a
      mixed-method design comprising a three-armed prospective randomized controlled
      trial and qualitative interviews with study data collected at three time points:
      baseline, after 4 months, and after 1 year. The patients' registrations on the
      application are recorded continuously and are sent securely to a server. RESULTS:
      The inclusion of patients started in March 2011, and 100% of the planned sample
      size is included (N=151). Of all the participants, 26/151 patients (17.2%) are
      lost to follow-up by now, and 11/151 patients (7.3%) are still in the trial.
      Results of the study protocol will be presented in 2014. CONCLUSIONS: The key
      goals of this trial are to investigate the effect of an electronic diabetes diary
      app with and without health counseling, and to determine whether health
      counseling is important to the continued use of the application and the patients'
      health competence and acceptability. Research within this area is needed because
      few studies have investigated the effectiveness of apps used in long-term
      interventions with this degree of self-management. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT01315756; http://clinicaltrials.gov/ct2/show/NCT01315756
      (Archived by WebCite at http://www.webcitation/6BTyuRMpH).

PMID- 23978691
TI  - Alteration in community-dwelling older adults' level walking following
      perturbation training.
AB  - While perturbation training is promising in reducing fall-risk among older
      adults, its impact on altering their spontaneous gait pattern has not been
      investigated. The purpose of this study was to determine to what extent older
      adults' gait pattern would be affected by exposure to repeated slips. Seventy
      three community-dwelling older adults (age: 72.6+/-5.4 years) underwent 24
      repeated-slip exposure induced by unannounced unlocking and relocking of low
      friction sections of a 7-m pathway upon which they walked. Full body kinematics
      and kinetics were recorded during the training. The gait parameters and the
      center of mass (COM) stability against backward balance loss were compared before
      and after the training. The results revealed that the training reduced fall
      incidence from 43.8% upon the novel slip to 0 at the end of training. After the
      training, subjects significantly improved gait stability by forward positioning
      of their COM relative to the base of support without altering gait speed. This
      forward COM shift resulted from a shortened step at the end of single stance and
      forward trunk leaning during double stance. They also adopted flat foot landing
      with knee flexed at touchdown (with an average change of 6.9 and 4.1 degrees,
      respectively). The perturbation training did alter community-dwelling older
      adults' spontaneous gait pattern. These changes enabled them to improve their
      volitional control of stability and their resistance to unpredictable and
      unpreventable slip-related postural disturbance. 

PMID- 23978692
TI  - Elbow joint biomechanics for preclinical evaluation of total elbow prostheses.
AB  - Total elbow arthroplasty is a clinically successful procedure, yet long-term
      implant survival rates have historically lagged behind those reported for total
      hips and knees. Clinical complications associated with implant wear, osteolysis,
      stem loosening and device fracture have been implicated as reasons for limited
      long-term survivorship. Unfortunately, there is little published information on
      the biomechanics and method(s) for preclinical evaluation of total elbow
      prostheses that could provide insight into the mechanisms of failure.
      Additionally, there are no consensus testing standards or summaries of loading
      profiles of the humero-ulnar joint associated with a range of activities of daily
      living. Such data would facilitate the standardized preclinical assessment of
      total elbow devices such is commonplace for other large joints. The objective of
      the work here is therefore to provide a comprehensive review of elbow joint
      biomechanics as it relates to preclinical evaluation of total elbow implants.
      This summary includes a review of elbow joint forces, kinematics, the types and
      frequency of humero-ulnar joint motions associated with activities of daily
      living and clinical outcomes, as well as proposing a methodology for deriving
      humero-ulnar joint reaction force magnitudes and vector orientations as a
      function of a known mass/force at the hand. From these data, a scalable, bi-axial
      loading profile is proposed as a foundation for the development of clinically
      relevant, laboratory simulations for assessment of total elbow prostheses
      performance. 

PMID- 23978694
TI  - The effects of a concurrent motor task on walking in Alzheimer's disease.
AB  - The important relationship between cognition and gait in people with dementia has
      been explored with dual-task studies using added cognitive tasks. Effects of less
      commonly studied but also attention-dividing motor dual-tasks are important to
      assess in this group as they are common in everyday function and may affect gait
      differently from cognitive dual-tasks. They may also be easier to comprehend
      allowing their application with more severe cognitive impairment. The aim of this
      study was to evaluate the effects and feasibility of a motor dual-task (MDT) on
      gait measures in people with Alzheimer's disease (AD). Thirty people (15 men,
      mean age +/- SD, 80.2 +/- 5.8 years) with a diagnosis of probable AD (MMSE range
      8-28) walked on an electronic walkway (i) at self-selected comfortable pace and
      (ii) at self-selected comfortable pace while carrying a tray and glasses. The MDT
      produced significant decreases in velocity (Baseline=111.5 +/- 26.5 cm/s,
      MDT=96.8 +/- 25.7 cm/s, p<0.001) and stride length (Baseline=121.4 +/- 21.6 cm,
      MDT=108.1 +/- 21.0 cm, p<0.001) with medium effect sizes, and increased stride
      time (Baseline=1.11 +/- 0.11s, MDT=1.14 +/- 0.12s, p=0.001) with small effect
      size. Measures of spatial (Baseline=3.2 +/- 1.0%, MDT=3.9 +/- 1.5%, p=0.006) and
      temporal (Baseline=2.4 +/- 0.8%, MDT=2.8 +/- 0.8%, p=0.008) variability increased
      with the motor dual-task, with medium effect sizes. A trend for motor dual-task
      changes in gait measures to increase with greater disease severity did not reach
      significance. The tray-carrying task was feasible, even for participants with
      severe cognitive decline. Further comparison of different types of motor and
      cognitive dual-tasks may contribute to development of a framework for clinical
      intervention to improve reduced dual-task walking capacity in people with AD.

PMID- 23978695
TI  - Young men utilise limited neuromuscular preparation to regulate post-impact knee
      mechanics during step landing.
AB  - PURPOSE: The neuromuscular mechanisms determining the mechanical behaviour of the
      knee during landing impact remain poorly understood. It was hypothesised that
      neuromuscular preparation is subject-specific and ranges along a continuum from
      passive to active. METHODS: A group of healthy men (N=12) stepped-down from a
      knee-high platform for 60 consecutive trials. Surface EMG of the quadriceps and
      hamstrings was used to determine pre-impact onset timing, activation amplitude
      and cocontraction for each trial. Partial least squares regression was used to
      associate pre-impact preparation with post-impact knee stiffness and
      coordination. RESULTS: The group analysis revealed few significant changes in pre
      impact preparation across trial blocks. Single-subject analyses revealed changes
      in muscle activity that varied in size and direction between individuals.
      Further, the association between pre-impact preparation and post-impact knee
      mechanics was subject-specific and ranged along a continuum of strategies.
      CONCLUSION: The findings suggest that neuromuscular preparation during step
      landing is subject-specific and its association to post-impact knee mechanics
      occurs along a continuum, ranging from passive to active control strategies.
      Further work should examine the implications of these strategies on the
      distribution of knee forces in vivo.

PMID- 23978693
TI  - Insulin status and vascular responses to weight loss in obesity.
AB  - OBJECTIVES: The aim of this study was to determine whether the effects of weight
      loss on arterial function are differentially modified by insulin status.
      BACKGROUND: Clinical studies suggest that plasma insulin levels may predict the
      extent of cardiovascular benefit achieved with weight loss in obese individuals,
      but mechanisms are currently unknown. METHODS: We prospectively followed 208
      overweight or obese patients (body mass index [BMI] >=25 kg/m(2)) receiving
      medical/dietary (48%) or bariatric surgical (52%) weight-loss treatment during a
      median period of 11.7 months (interquartile range: 4.6 to 13 months). We measured
      plasma metabolic parameters and vascular endothelial function using ultrasound at
      baseline and following weight-loss intervention and stratified analyses by median
      plasma insulin levels. RESULTS: Patients age 45 +/- 1 years, with BMI 45 +/- 9
      kg/m(2), experienced 14 +/- 14% weight loss during the study period. In
      individuals with higher baseline plasma insulin levels (above median >12 MUIU/ml;
      n = 99), >=10% weight loss (compared with <10%) significantly improved brachial
      artery macrovascular flow-mediated vasodilation and microvascular reactive
      hyperemia (p < 0.05 for all). By contrast, vascular function did not change
      significantly in the lower insulin group (<=12 MUIU/ml; n = 109) despite a
      similar degree of weight loss. In analyses using a 5% weight loss cut point, only
      microvascular responses improved in the higher insulin group (p = 0.02).
      CONCLUSIONS: Insulin status is an important determinant of the positive effect of
      weight reduction on vascular function with hyperinsulinemic patients deriving the
      greatest benefit. Integrated improvement in both microvascular and macrovascular
      function was associated with >=10% weight loss. Reversal of insulin resistance
      and endothelial dysfunction may represent key therapeutic targets for
      cardiovascular risk reduction in obesity.

PMID- 23978696
TI  - Outcomes after tongue-lip adhesion or mandibular distraction osteogenesis in
      infants with Pierre Robin sequence and severe airway obstruction.
AB  - The objective was to review and compare outcomes after tongue-lip adhesion (TLA)
      and mandibular distraction osteogenesis (MDO) in infants with severe breathing
      difficulties related to Pierre Robin sequence (PRS). A single-centre
      retrospective (2002-2012) study was carried out; 18 infants with severe breathing
      difficulties related to PRS resistant to conservative treatment, who underwent
      TLA or MDO to correct airway obstruction, were enrolled. The primary outcome
      measures were successful weaning from respiratory support and resumption of full
      oral feeding. Nine underwent TLA and nine MDO. Eight of the nine infants who
      underwent MDO and all those treated with TLA were successfully weaned from
      respiratory support. After discharge, residual respiratory distress was diagnosed
      more commonly after TLA than after MDO (6/9 vs 1/9, P=0.050). Infants resumed
      oral feeding sooner after MDO than after TLA (mean days after surgery to full
      oral feeds 44+/-24 vs 217+/-134, P<0.003). The length of hospital stay was longer
      for infants treated with MDO than for those treated with TLA. The rate of
      complications was similar. Infants with severe airway obstruction related to PRS
      can benefit safely from either TLA or MDO. Although MDO lengthens the time to
      discharge, this option stabilizes airway patency of infants with PRS more
      efficiently and achieves full oral feeding more rapidly than TLA. 

PMID- 23978697
TI  - Type 2 ryanodine receptor domain A contains a unique and dynamic alpha-helix that
      transitions to a beta-strand in a mutant linked with a heritable cardiomyopathy.
AB  - Ryanodine receptors (RyRs) are large tetrameric calcium (Ca(2+)) release channels
      found on the sarcoplasmic reticulum that respond to dihydropyridine receptor
      activity through a direct conformational interaction and/or indirect Ca(2+)
      sensitivity, propagating sarcoplasmic reticulum luminal Ca(2+) release in the
      process of excitation-contraction coupling. There are three human RyR subtypes,
      and several debilitating diseases are linked to heritable mutations in RyR1 and
      RyR2 including malignant hypothermia, central core disease, catecholaminergic
      polymorphic ventricular tachycardia (CPVT) and arrhythmogenic right ventricular
      dysplasia type 2 (ARVD2). Despite the recent appreciation that many disease
      associated mutations within the N-terminal RyRABC domains (i.e., residues 1-559)
      are located in the putative interfaces mediating tetrameric channel assembly, the
      precise structural and dynamical consequences of the mutations are not well
      understood. We used solution nuclear magnetic resonance (NMR) spectroscopy and X
      ray crystallography to examine the effect of ARVD2-associated (i.e., R176Q) and
      CPVT-associated [i.e., P164S, R169Q and delta exon 3 (Delta3)] mutations on the
      structure and dynamics of RyR2A. Our solution NMR data exposed a mobile alpha
      helix, unique to type 2; further, this alpha2 helix rescues the beta-strand lost
      in RyR2A Delta3 but remains dynamic in the hot-spot loop (HS-loop) P164S, R169Q
      and R176Q mutant proteins. Docking of our X-ray crystal/NMR hybrid structure into
      the RyR1 cryo-electron microscopy map revealed that this RyR2A alpha2 helix is in
      close proximity to dense "columns" projecting toward the channel pore. This is in
      contrast to the HS-loop mutations that cause structural changes largely localized
      to the intersubunit interface between adjacent ABC domains. Taken together, our
      data suggest that ARVD2 and CPVT mutations have at least two distinct structural
      consequences linked to channel dysfunction: perturbation of the HS-loop (i.e.,
      domain A):domain B intersubunit interface and disruption of the communication
      between the N-terminal region and the channel domain.

PMID- 23978699
TI  - [Contribution of imaging in the diagnosis of epiploic appendagitis].
AB  - INTRODUCTION: Primary epiploic appendagitis is known to be a rare finding among
      causes of acute abdomen. Depending on location, it may mimic several disorders
      such as colonic diverticulitis and acute appendicitis. Diagnosis is sometimes
      performed during surgery. METHODS: This is a retrospective descriptive study. The
      authors report the contribution of imaging for the diagnosis of appendagitis in
      seven patients investigated between July 2010 and April 2013 by abdominal and
      pelvic ultrasound or computed tomography (CT). RESULTS: CT scan confirmed the
      diagnosis in six patients avoiding unnecessary surgery and hospitalization. The
      seventh patient was a pregnant woman in whom the diagnosis of appendagitis was
      made during surgery for appendicitis. CONCLUSION: Appendagitis is a rare cause of
      acute abdominal pain. Outcome is favorable with medical treatment only. Abdominal
      ultrasound and CT are helpful diagnostic tests avoiding useless surgical
      procedure.

PMID- 23978700
TI  - Comprehensive monitoring of synthetic musk compounds from freshwater to coastal
      environments in Korea: with consideration of ecological concerns and
      bioaccumulation.
AB  - This study investigated the concentration levels of synthetic musk compounds
      (SMCs), including HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta
      (g)-2-benzopyran), AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4
      tetrahydronaphthalene), MK (Musk ketone), and MX (Musk xylene), in freshwater,
      freshwater and coastal sediments, and coastal bivalves from freshwater to coastal
      environments. The levels in freshwater close to sewage treatment plants (STPs)
      showed higher contamination and suggested a medium to high ecological risk,
      especially posed by MK making more than 65% contribution to the combined risk by
      the total SMCs. STP effluent discharge points showed higher SMC concentrations in
      freshwater and coastal sediments. Predominant HHCB contributions regardless of
      sample types such as abiota and biota were consistent with the greater usage of
      HHCB than AHTN and MK in Korea. However, the higher contributions of AHTN than
      those predicted from AHTN consumption in Korea indicate the need for further
      research on the characteristic properties of individual SMCs, including
      partitioning, biomagnification, degradation, and metabolism for a realistic risk
      characterization. With respect to the highest HHCB levels in coastal bivalves
      reported, we determined the biota-sediment accumulation factor (BSAF) to
      understand the bioaccumulation of SMCs between coastal sediment and bivalves. The
      calculated BSAF values suggested that SMCs in bivalves were not biomagnified via
      the food chain but mostly partitioned from sediment. To our knowledge, this is
      the first study to measure BSAF values of SMCs, especially HHCB, AHTN, and MK, in
      coastal bivalve samples. 

PMID- 23978701
TI  - Spatial and temporal trends in occurrence of emerging and legacy contaminants in
      the Lower Columbia River 2008-2010.
AB  - The Lower Columbia River in Oregon and Washington, USA, is an important resource
      for aquatic and terrestrial organisms, agriculture, and commerce. An 86-mile
      stretch of the river was sampled over a 3year period in order to determine the
      spatial and temporal trends in the occurrence and concentration of water-borne
      organic contaminants. Sampling occurred at 10 sites along this stretch and at 1
      site on the Willamette River using the semipermeable membrane device (SPMD) and
      the polar organic chemical integrative sampler (POCIS) passive samplers.
      Contaminant profiles followed the predicted trends of lower numbers of detections
      and associated concentrations in the rural areas to higher numbers and
      concentrations at the more urbanized sites. Industrial chemicals, plasticizers,
      and PAHs were present at the highest concentrations. Differences in
      concentrations between sampling periods were related to the amount of rainfall
      during the sampling period. In general, water concentrations of wastewater
      related contaminants decreased and concentrations of legacy contaminants slightly
      increased with increasing rainfall amounts. 

PMID- 23978698
TI  - Malachite green mediates homodimerization of antibody VL domains to form a
      fluorescent ternary complex with singular symmetric interfaces.
AB  - We report that a symmetric small-molecule ligand mediates the assembly of
      antibody light chain variable domains (VLs) into a correspondent symmetric
      ternary complex with novel interfaces. The L5* fluorogen activating protein is a
      VL domain that binds malachite green (MG) dye to activate intense fluorescence.
      Crystallography of liganded L5* reveals a 2:1 protein:ligand complex with
      inclusive C2 symmetry, where MG is almost entirely encapsulated between an
      antiparallel arrangement of the two VL domains. Unliganded L5* VL domains
      crystallize as a similar antiparallel VL/VL homodimer. The complementarity
      determining regions are spatially oriented to form novel VL/VL and VL/ligand
      interfaces that tightly constrain a propeller conformer of MG. Binding
      equilibrium analysis suggests highly cooperative assembly to form a very stable
      VL/MG/VL complex, such that MG behaves as a strong chemical inducer of
      dimerization. Fusion of two VL domains into a single protein tightens MG binding
      over 1000-fold to low picomolar affinity without altering the large binding
      enthalpy, suggesting that bonding interactions with ligand and restriction of
      domain movements make independent contributions to binding. Fluorescence
      activation of a symmetrical fluorogen provides a selection mechanism for the
      isolation and directed evolution of ternary complexes where unnatural symmetric
      binding interfaces are favored over canonical antibody interfaces. As exemplified
      by L5*, these self-reporting complexes may be useful as modulators of protein
      association or as high-affinity protein tags and capture reagents. 

PMID- 23978702
TI  - Radiographic measures of the mid pelvis to predict cesarean delivery.

PMID- 23978704
TI  - Discussion: 'Gestational weight gain and hypertensive disorders,' by MacDonald
      Wallis et al.
AB  - In the roundtable that follows, clinicians discuss a study published in this
      issue of the Journal in light of its methodology, relevance to practice, and
      implications for future research.

PMID- 23978705
TI  - Alkaline and ultrasound assisted alkaline pretreatment for intensification of
      delignification process from sustainable raw-material.
AB  - Alkaline and ultrasound-assisted alkaline pretreatment under mild operating
      conditions have been investigated for intensification of delignification. The
      effect of NaOH concentration, biomass loading, temperature, ultrasonic power and
      duty cycle on the delignification has been studied. Most favorable conditions for
      only alkaline pretreatment were alkali concentration of 1.75 N, solid loading of
      0.8% (w/v), temperature of 353 K and pretreatment time of 6 h and under these
      conditions, 40.2% delignification was obtained. In case of ultrasound-assisted
      alkaline approach, most favorable conditions obtained were alkali concentration
      of 1N, paper loading of 0.5% (w/v), sonication power of 100 W, duty cycle of 80%
      and pretreatment time of 70 min and the delignification obtained in ultrasound
      assisted alkaline approach under these conditions was 80%. The material samples
      were characterized by FTIR, SEM, XRD and TGA technique. The lignin was recovered
      from solution by precipitation method and was characterized by FTIR, GPC and TGA
      technique.

PMID- 23978706
TI  - All-inside arthroscopic lateral collateral ligament repair for ankle instability
      with a knotless suture anchor technique.
AB  - BACKGROUND: Recently, arthroscopic-assisted techniques have been described to
      treat lateral ankle instability with excellent results. However, complications
      including neuritis of the superficial peroneal or sural nerve, and pain or
      discomfort due to a prominent anchor or suture knot have been reported. The aim
      of this study was to describe a novel technique, the "all-inside arthroscopic
      lateral collateral ankle ligament repair," and its results for treating patients
      with ankle instability. METHODS: Sixteen patients (10 men and 6 women, mean age
      29.3 years, 17-46) with lateral ankle instability were treated with an
      arthroscopic procedure. Using a suture passer and a knotless anchor, the
      ligaments were repaired with an all-inside technique. The right ankle was
      affected in 10 cases. Mean follow-up was 22.3 (12-35) months. RESULTS: On
      arthroscopic examination, 13 patients had an isolated anterior talofibular
      ligament (ATFL) injury, and in 3 patients, both the ATFL and calcaneofibular
      ligament (CFL) were affected. All-inside arthroscopic anatomic repair of the
      lateral collateral ligament complex was performed in all cases. All patients
      reported subjective improvement of their ankle instability. The mean AOFAS score
      increased from 67 preoperatively to 97 at final follow-up. No major complications
      were reported. CONCLUSION: The all-inside arthroscopic ligament repair was a
      safe, reliable, and reproducible technique that both provided an anatomic repair
      of the lateral collateral ligament complex and restored ankle stability while
      preserving all the advantages of an arthroscopic technique. LEVEL OF EVIDENCE:
      Level IV, retrospective case series.

PMID- 23978707
TI  - Flexor digitorum brevis transfer for floating toe prevention after Weil
      osteotomy: a cadaveric study.
AB  - BACKGROUND: A floating toe deformity occurs in many patients who undergo Weil
      osteotomies. It is likely caused by the failure of the windlass mechanism in
      shortening the metatarsal. For patients who require a proximal interphalangeal
      (PIP) joint arthroplasty or fusion in addition to a Weil osteotomy, the transfer
      of the flexor digitorum brevis (FDB) tendon to the PIP joint might restore the
      windlass mechanism and decrease the incidence of floating toes. METHODS: Fourteen
      cadaveric foot specimens were examined to determine the effects of changing
      metatarsal length as well as tensioning the FDB tendon on the angle of the
      metatarsophalangeal (MTP) joint as a measure of a floating toe. RESULTS:
      Shortening and lengthening the second metatarsal resulted in a significant change
      in MTP angle (P = .03 and .02, respectively), though there was no clear
      relationship found between the amount of change in metatarsal length and the
      change in MTP angle. Transferring the FDB to a PIP arthroplasty site
      plantarflexed the MTP joint and corrected floating toes; the change in angle was
      significant compared with the control and shortening groups (P = .0001 and .002,
      respectively). CONCLUSION: This study supports the theory that change in length
      of the metatarsal, possibly via the windlass mechanism, plays a role in the
      pathophysiology of the floating toe deformity. Tensioning and transferring the
      FDB tendon into the PIP joint helped prevent the floating toe deformity in this
      cadaveric model. CLINICAL RELEVANCE: Continued research in this subject will help
      to refine methods of prevention and correction of the floating toe deformity.

PMID- 23978708
TI  - Dosimetric and radiobiological consequences of computed tomography-guided
      adaptive strategies for intensity modulated radiation therapy of the prostate.
AB  - PURPOSE: To examine a range of scenarios for image-guided adaptive radiation
      therapy of prostate cancer, including different schedules for megavoltage CT
      imaging, patient repositioning, and dose replanning. METHODS AND MATERIALS: We
      simulated multifraction dose distributions with deformable registration using 35
      sets of megavoltage CT scans of 13 patients. We computed cumulative dose-volume
      histograms, from which tumor control probabilities and normal tissue complication
      probabilities (NTCPs) for rectum were calculated. Five-field intensity modulated
      radiation therapy (IMRT) with 18-MV x-rays was planned to achieve an isocentric
      dose of 76 Gy to the clinical target volume (CTV). The differences between D95,
      tumor control probability, V70Gy, and NTCP for rectum, for accumulated versus
      planned dose distributions, were compared for different target volume sizes,
      margins, and adaptive strategies. RESULTS: The CTV D95 for IMRT treatment plans,
      averaged over 13 patients, was 75.2 Gy. Using the largest CTV margins (10/7 mm),
      the D95 values accumulated over 35 fractions were within 2% of the planned value,
      regardless of the adaptive strategy used. For tighter margins (5 mm), the average
      D95 values dropped to approximately 73.0 Gy even with frequent repositioning, and
      daily replanning was necessary to correct this deficit. When personalized margins
      were applied to an adaptive CTV derived from the first 6 treatment fractions
      using the STAPLE (Simultaneous Truth and Performance Level Estimation) algorithm,
      target coverage could be maintained using a single replan 1 week into therapy.
      For all approaches, normal tissue parameters (rectum V(70Gy) and NTCP) remained
      within acceptable limits. CONCLUSIONS: The frequency of adaptive interventions
      depends on the size of the CTV combined with target margins used during IMRT
      optimization. The application of adaptive target margins (<5 mm) to an adaptive
      CTV determined 1 week into therapy minimizes the need for subsequent dose
      replanning.

PMID- 23978709
TI  - Local recurrence after curettage treatment of giant cell tumors in peripheral
      bones: retrospective study by the GSF-GETO (French Sarcoma and Bone Tumor Study
      Groups).
AB  - BACKGROUND: Curettage is a well-established treatment modality for giant cell
      tumors of bone. The purpose of this retrospective study by the French Sarcoma and
      Bone Tumor Study Groups (GSF-GETO) was to analyze various tumor-specific and
      surgery-specific factors that could influence the rate of local recurrence.
      PATIENTS AND METHOD: Data was collected from patients with giant cells tumors of
      the appendicular skeletal who were treated by intralesional curettage. The hazard
      ratio for tumor recurrence was calculated for the different variables collected
      and a multifactorial analysis carried out. RESULTS: One hundred and ninety-three
      surgical procedures were included from nine centers. One hundred and seventy-one
      (89%) were primary tumors and 22 had been referred after one or more recurrences.
      The mean follow-up was 6 years and 11 months. The distal femur and proximal tibia
      were the most common locations: 42.5 and 34.2% of cases, respectively. The bone
      defect after curettage was filled in 176 cases (91.2%) and left empty in 16
      cases. Local adjuvant treatment (phenol, alcohol, cryotherapy or combination
      treatment) was used in 39 cases (20.2%) and systemic adjuvant treatment used in
      24 cases (calcitonin 11 and zoledronic acid 13). Local recurrence occurred in 71
      cases (36.8%). Risk factors for local recurrence were an empty defect, a defect
      filled with autograft, and patients treated before 2005. Multivariate analysis
      showed that the only risk factors for local recurrence were a surgical procedure
      before 2005 (odds ratio 3.6 (95% CI: 1.2, 7.9) P=0.017) and a bone defect filled
      with autograft (odds ratio 3.9 [95% CI: 1.3, 11.6] P=0.013) CONCLUSION: Neither
      tumor-specific nor surgery-specific factors such as adjuvant treatment were found
      to be as risk factors for local recurrence after curettage of giant cell tumors
      in the appendicular skeleton. As recently reported, high-quality local curettage
      is probably the most effective technique to prevent local recurrence. The current
      study suggests that two factors associated with more recent management of these
      tumors in France, high-speed burring and centralization to skilled surgical
      teams, can improve the quality of curettage. LEVEL OF EVIDENCE: 4, retrospective
      cohort study.

PMID- 23978710
TI  - The talonavicular and subtalar joints: the "calcaneopedal unit" concept.
AB  - The talonavicular (TN) joint and the three subtalar (ST) joints are linked
      anatomically and functionally. Together they form the subtalar joint complex,
      where movement occurs between the calcaneopedal unit (CPU) (entire foot except
      the talus) and the talotibiofibular unit (talus held tightly by the ankle
      mortise). Many are unaware of the TN joint's dual membership: it is a component
      of the subtalar joint complex (talocalcaneonavicular joint) and also the
      transverse tarsal joint (with the calcaneal-cuboid joint). The anatomy of the
      articulating surfaces, movement of the CPU when unloaded, shifts and changes in
      CPU shape with weight bearing, application to clinical tests and X-ray
      interpretation, and the pathophysiology applications to pes cavovarus, pes
      planovalgus and congenital talipes equinovarus (club foot) will be reviewed here.
      The CPU concept corresponds to a horizontal segmentation of the foot. This is a
      useful supplement to the two other segmentation methods: frontal (hindfoot,
      midfoot and forefoot) and sagittal (medial and lateral columns). This horizontal
      segmentation solves the issues with the ST joint complex, which straddles the
      hindfoot and midfoot, and also the issues with the dual membership of the TN
      joint. This concept makes it easier to understand foot deformities, better
      interpret the clinical and radiological signs and deduce logical treatments. 

PMID- 23978711
TI  - Histologic study of periprosthetic osteolytic lesions after AES total ankle
      replacement. A 22 case series.
AB  - INTRODUCTION: Medium-term results for total ankle replacement (TAR) are in
      general satisfactory, but there is a high redo rate for periprosthetic osteolysis
      associated with the AES implant. HYPOTHESIS: Comparing radioclinical findings and
      histologic analysis of implant revision procedure specimens can account for the
      elevated rate of osteolysis associated with the AES TAR implant. MATERIAL AND
      METHOD: In a prospective series of 84 AES TAR implants (2003-2008), 25 underwent
      revision for osteolysis (including three undergoing revision twice) at a mean
      59.8 months. Eight patients had hydroxyapatite (HA) coated models and the others
      had titanium-hydroxyapatite (Ti-HA) coatings. Radiographs were systematically
      analyzed on Besse's protocol and evolution was monitored on AOFAS scores. The 94
      specimens taken for histologic analysis during revision were re-examined,
      focusing specifically on foreign bodies. RESULTS: Macroscopically, no metallosis
      or polyethylene wear was found at revision. AOFAS global and pain scores fell
      respectively from 89.7/100 at 1 year postoperatively to 72.9 before revision and
      from 32.5/40 to 20.6/40, although global scores were unchanged in 25% of
      patients. Radiologically, all patients showed tibial and talar osteolytic
      lesions, 45% showed cortical lysis and in 25% the implant had collapsed into the
      cysts. All specimens showed macrophagic granulomatous inflammatory reactions in
      contact with a foreign body; the cysts showed necrotic remodeling. Some of the
      foreign bodies could be identified on optical histologic examination with
      polyethylene in 95% of the specimens and metal in 60% (100% of HA-coated models
      and 33.3% of Ti-HA-coated models). Unidentifiable material was associated: a
      brownish pigment in Ti-HA-coated models (33.3%) and flakey bodies in 44.4% of the
      HA-coated models and 18.2% of the Ti-HA-coated models. DISCUSSION: The phenomenon
      of periprosthetic osteolysis is still poorly understood, although implant wear
      debris seems to be implicated. All the patients with HA-coated implants with
      modular tibial stem had metal particles in the tissue around the implant,
      although their exact nature could not be determined. The double-layer Ti-HA
      coating may induce delamination by fretting while the biological bone anchorage
      is forming. LEVEL OF EVIDENCE: Prospective cohort study - Level IV.

PMID- 23978712
TI  - Hepatitis C virus modulates lipid regulatory factor Angiopoietin-like 3 gene
      expression by repressing HNF-1alpha activity.
AB  - BACKGROUND & AIMS: HCV relies on host lipid metabolism to complete its life cycle
      and HCV core is crucial to this interaction. Liver secreted ANGPTL-3 is an LXR-
      and HNF-1alpha-regulated protein, which plays a key role in lipid metabolism by
      increasing plasma lipids via inhibition of lipase enzymes. Here we aimed to
      investigate the modulation of ANGPTL-3 by HCV core and identify the molecular
      mechanisms involved. METHODS: qRT-PCR and ELISA were used to assess ANGPTL-3 mRNA
      and protein levels in HCV patients, the JFH-1 infectious system and liver cell
      lines. Transfections, chromatin immunoprecipitation and immunofluorescence
      delineated parts of the molecular mechanisms implicated in the core-mediated
      regulation of ANGPTL-3 gene expression. RESULTS: ANGPTL-3 gene expression was
      decreased in HCV-infected patients and the JFH-1 infectious system. mRNA and
      promoter activity levels were down-regulated by core. The response was lost when
      an HNF-1alpha element in ANGPTL-3 promoter was mutated, while loss of HNF-1alpha
      DNA binding to this site was recorded in the presence of HCV core. HNF-1alpha
      mRNA and protein levels were not altered by core. However, trafficking between
      nucleus and cytoplasm was observed and then blocked by an inhibitor of the HNF
      1alpha-specific kinase Mirk/Dyrk1B. Transactivation of LXR/RXR signalling could
      not restore core-mediated down-regulation of ANGPTL-3 promoter activity.
      CONCLUSIONS: ANGPTL-3 is negatively regulated by HCV in vivo and in vitro. HCV
      core represses ANGPTL-3 expression through loss of HNF-1alpha binding activity
      and blockage of LXR/RXR transactivation. The putative ensuing increase in serum
      lipid clearance and uptake by the liver may sustain HCV virus replication and
      persistence.

PMID- 23978713
TI  - The intrahepatic signalling niche of hedgehog is defined by primary cilia
      positive cells during chronic liver injury.
AB  - BACKGROUND & AIMS: In vertebrates, canonical Hedgehog (Hh) pathway activation
      requires Smoothened (SMO) translocation to the primary cilium (Pc), followed by a
      GLI-mediated transcriptional response. In addition, a similar gene regulation
      occurs in response to growth factors/cytokines, although independently of SMO
      signalling. The Hh pathway plays a critical role in liver fibrosis/regeneration,
      however, the mechanism of activation in chronic liver injury is poorly
      understood. This study aimed to characterise Hh pathway activation upon
      thioacetamide (TAA)-induced chronic liver injury in vivo by defining Hh
      responsive cells, namely cells harbouring Pc and Pc-localised SMO. METHODS:
      C57BL/6 mice (wild-type or Ptc1(+/-)) were TAA-treated. Liver injury and Hh
      ligand/pathway mRNA and protein expression were assessed in vivo. SMO/GLI
      manipulation and SMO-dependent/independent activation of GLI-mediated
      transcriptional response in Pc-positive (Pc(+)) cells were studied in vitro.
      RESULTS: In vivo, Hh activation was progressively induced following TAA. At the
      epithelial-mesenchymal interface, injured hepatocytes produced Hh ligands.
      Progenitors, myofibroblasts, leukocytes and hepatocytes were GLI2(+). Pc(+) cells
      increased following TAA, but only EpCAM(+)/GLI2(+) progenitors were Pc(+)/SMO(+).
      In vitro, SMO knockdown/hGli3-R overexpression reduced proliferation/viability in
      Pc(+) progenitors, whilst increased proliferation occurred with hGli1
      overexpression. HGF induced GLI transcriptional activity independently of Pc/SMO.
      Ptc1(+/-) mice exhibited increased progenitor, myofibroblast and fibrosis
      responses. CONCLUSIONS: In chronic liver injury, Pc(+) progenitors receive Hh
      ligand signals and process it through Pc/SMO-dependent activation of GLI-mediated
      transcriptional response. Pc/SMO-independent GLI activation likely occurs in Pc(
      )/GLI2(+) cells. Increased fibrosis in Hh gain-of-function mice likely occurs by
      primary progenitor expansion/proliferation and secondary fibrotic myofibroblast
      expansion, in close contact with progenitors.

PMID- 23978714
TI  - Non-cirrhotic portal hypertension - diagnosis and management.
AB  - NCPH is a heterogeneous group of liver disorders of vascular origin, leading to
      PHT with near normal HVPG. NCPF/IPH is a disorder of young adults or middle aged
      women, whereas EHPVO is a disorder of childhood. Early age acute or recurrent
      infections in an individual with thrombotic predisposition constitute the likely
      pathogenesis. Both disorders present with clinically significant PHT with
      preserved liver functions. Diagnosis is easy and can often be made clinically
      with support from imaging modalities. Management centers on control and
      prophylaxis of variceal bleeding. In EHPVO, there are additional concerns of
      growth faltering, portal biliopathy, MHE and parenchymal dysfunction. Surgical
      shunts are indicated in patients with failure of endotherapy, bleeding from sites
      not amenable to endotherapy, symptomatic hypersplenism or symptomatic biliopathy.
      Persistent growth failure, symptomatic and recurrent hepatic encephalopathy,
      impaired quality of life or massive splenomegaly that interferes with daily
      activities are other surgical indications. Rex-shunt or MLPVB is the recommended
      shunt for EHPVO, but needs proper pre-operative radiological assessment and
      surgical expertise. Both disorders have otherwise a fairly good prognosis, but
      need regular and careful surveillance. Hepatic schistosomiasis, CHF and NRH have
      similar presentation and comparable prognosis. 

PMID- 23978716
TI  - Hepatitis C-associated B-cell non-Hodgkin lymphomas: the emerging role of miRNA
      26b.

PMID- 23978715
TI  - Deleterious effect of oltipraz on extrahepatic cholestasis in bile duct-ligated
      mice.
AB  - BACKGROUND & AIMS: Oltipraz (4-methyl-5(pyrazinyl-2)-1-2-dithiole-3-thione), a
      promising cancer preventive agent, has an antioxidative activity and ability to
      enhance glutathione biosynthesis, phase II detoxification enzymes and multidrug
      resistance-associated protein-mediated efflux transporters. Oltipraz can protect
      against hepatotoxicity caused by carbon tetrachloride, acetaminophen and alpha
      naphthylisothiocyanate. Whether oltipraz has hepato-protective effects on
      obstructive cholestasis is unknown. METHODS: We administered oltipraz to mice for
      5 days prior to bile duct ligation (BDL) for 3 days. Liver histology, liver
      function markers, bile flow rates and hepatic expression of profibrogenic genes
      were evaluated. RESULTS: Mice pretreated with oltipraz prior to BDL demonstrated
      higher levels of serum aminotransferases and more severe liver damage than in
      control mice. Higher bile flow and glutathione secretion rates were observed in
      unoperated mice treated with oltipraz than in control mice, suggesting that liver
      necrosis in oltipraz-treated BDL mice may be related partially to increased bile
      acid independent flow and biliary pressure. Oltipraz treatment in BDL mice
      enhanced alpha-smooth muscle actin expression, consistent with activation of
      hepatic stellate cells and portal fibroblasts. Matrix metalloproteinases (Mmp) 9
      and 13 and tissue inhibitors of metalloproteinases (Timp) 1 and 2 levels were
      increased in the oltipraz-treated BDL group, suggesting that the secondary phase
      of liver injury induced by oltipraz might be due to excessive Mmp and Timp
      secretions, which induce remodeling of the extracellular matrix. CONCLUSIONS:
      Oltipraz treatment exacerbates the severity of liver injury following BDL and
      should be avoided as therapy for extrahepatic cholestatic disorders due to bile
      duct obstruction.

PMID- 23978717
TI  - Long-term follow-up of hepatitis C infection in a large cohort of patients with
      inherited bleeding disorders.
AB  - BACKGROUND & AIMS: Patients with inherited bleeding disorders are an interesting
      group to study the long-term course of chronic hepatitis C virus (HCV) infection,
      because of their uniform mode of infection and reliable follow-up. Our aim was to
      assess the long-term occurrence of adverse liver-related events in these
      patients. METHODS: The occurrence and determinants of end-stage liver disease
      (ESLD) were assessed using retrospective data of 863 HCV infected patients with
      inherited bleeding disorders from the Netherlands and the UK. RESULTS: Median
      follow-up since HCV infection was 31 years, while 30% of patients had >35 follow
      up years. Nineteen percent of patients spontaneously cleared the virus and 81%
      developed chronic HCV infection. Of the 700 patients with chronic HCV, 90 (13%)
      developed ESLD. Hepatocellular carcinoma (HCC) was diagnosed in 3% of patients
      with chronic HCV, 41% of which occurred in the last six years. Determinants of
      ESLD development were age at infection (hazard ratio (HR) 1.09 per year
      increase), HIV co-infection (HR 10.85), history of alcohol abuse (HR 4.34) and
      successful antiviral treatment (HR 0.14). Of the 487 patients who were still
      alive at the end of follow-up, 49% did not undergo optimal conventional antiviral
      treatment. CONCLUSIONS: After over 30 years of HCV infection, ESLD occurred in a
      significant proportion of patients with inherited bleeding disorders. HCC appears
      to be an increasing problem. There is a significant potential for both
      conventional and new antiviral treatment regimens to try and limit ESLD
      occurrence in the future.

PMID- 23978718
TI  - HLA-B*27 subtype specificity determines targeting and viral evolution of a
      hepatitis C virus-specific CD8+ T cell epitope.
AB  - BACKGROUND & AIMS: HLA-B*27 is associated with spontaneous HCV genotype 1
      clearance. HLA-B*27-restricted CD8+ T cells target three NS5B epitopes. Two of
      these epitopes are dominantly targeted in the majority of HLA-B*27+ patients. In
      chronic infection, viral escape occurs consistently in these two epitopes. The
      third epitope (NS5B2820) was dominantly targeted in an acutely infected patient.
      This was in contrast, however, to the lack of recognition and viral escape in the
      large majority of HLA-B*27+ patients. Here, we set out to determine the host
      factors contributing to selective targeting of this epitope. METHODS: Four-digit
      HLA class I typing and viral sequence analyses were performed in 78 HLA-B*27+
      patients with chronic HCV genotype 1 infection. CD8+ T cell analyses were
      performed in a subset of patients. In addition, HLA/peptide affinity was compared
      for HLA-B*27:02 and 05. RESULTS: The NS5B2820 epitope is only restricted by the
      HLA-B*27 subtype HLA-B*27:02 (that is frequent in Mediterranean populations), but
      not by the prototype HLA-B*27 subtype B*27:05. Indeed, the epitope is very
      dominant in HLA-B*27:02+ patients and is associated with viral escape mutations
      at the anchor position for HLA-binding in 12 out of 13 HLA-B*27:02+ chronically
      infected patients. CONCLUSIONS: The NS5B2820 epitope is immunodominant in the
      context of HLA-B*27:02, but is not restricted by other HLA-B*27 subtypes. This
      finding suggests an important role of HLA subtypes in the restriction of HCV
      specific CD8+ responses. With minor HLA subtypes covering up to 39% of specific
      populations, these findings may have important implications for the selection of
      epitopes for global vaccines.

PMID- 23978719
TI  - Hepatocellular cancer: the impact of obesity, type 2 diabetes and a
      multidisciplinary team.
AB  - BACKGROUND & AIMS: Hepatocellular cancer (HCC) commonly complicates chronic liver
      disease and increases in incidence have been reported despite falling prevalences
      of viral hepatitis. METHODS: Following the introduction of centralised specialist
      teams to manage patients with cancer in England, we characterised the
      demographics of patients with HCC referred to the Newcastle-upon-Tyne Hospitals
      NHS Foundation Trust between 2000 and 2010. Regional HCC mortality data was from
      Public Health England. RESULTS: HCC related mortality in the region rose 1.8 fold
      in 10 years, from 2.0 to 3.7 per 100,000. 632 cases were reviewed centrally, with
      2-3 fold increases in referrals of patients with associated hepatitis C,
      alcoholic liver disease or no chronic liver disease and a >10 fold increase in
      HCC associated with non-alcoholic fatty liver disease (NAFLD). By 2010 NAFLD
      accounted for 41/118 (34.8%) cases. Irrespective of associated etiologies,
      metabolic risk factors were present in 78/118 (66.1%) cases in 2010, associated
      with regional increases in obesity and diabetes. Median overall survival was just
      10.7 months. Although patients with NAFLD associated HCC were older (71.3 yr vs.
      67.1 yr; p<0.001) and their cancers less often detected by surveillance, their
      survival was similar to other etiologies. This was attributed to significantly
      higher incidental presentation (38.2%) and lower prevalence of cirrhosis (77.2%).
      CONCLUSIONS: HCC related mortality is increasing, with typical patients being
      elderly with metabolic risk factors. The prognosis for most of the cases is poor,
      but older patients with co-morbidities can do well, managed, within a specialist
      multidisciplinary team if their cancer is detected pre-symptomatically.

PMID- 23978721
TI  - Promoted degradation of perfluorooctanic acid by persulfate when adding activated
      carbon.
AB  - Treatment of persistent perfluorooctanoic acid (PFOA) in water using persulfate
      (PS) oxidation typically requires an elevated temperature or UV irradiation,
      which is energy-consuming. Under relatively low temperatures of 25-45 degrees C,
      activated carbon (AC) activated PS oxidation of PFOA was evaluated for its
      potential of practical applications. With presence of AC in PS oxidation, PFOA
      removal efficiency at 25 degrees C reached 682% with a high defluorination
      efficiency of 549% after 12h and few intermediates of short-chain perfluorinated
      carboxylic acids (PFCAs) were found. The removal and defluorination rates with
      the combined AC/PS system were approximately 12 and 19 times higher than those of
      the PS-only system, respectively. Activated carbon not only removes PFOA through
      adsorption, but also activates PS to form sulfate radicals that accelerate the
      decomposition and mineralization of PFOA. The activation energy for PS oxidation
      of PFOA was reduced from 668 to 261kJ/mol by the catalytic effect of AC, which
      implies a lower reaction temperature and a shorter reaction time would suffice. A
      2-cycle schematic reaction mechanism was used to describe PS oxidation of PFOA
      with the generation of various intermediates and end-products.

PMID- 23978722
TI  - Recent development in the treatment of oily sludge from petroleum industry: a
      review.
AB  - Oily sludge is one of the most significant solid wastes generated in the
      petroleum industry. It is a complex emulsion of various petroleum hydrocarbons
      (PHCs), water, heavy metals, and solid particles. Due to its hazardous nature and
      increased generation quantities around the world, the effective treatment of oily
      sludge has attracted widespread attention. In this review, the origin,
      characteristics, and environmental impacts of oily sludge were introduced. Many
      methods have been investigated for dealing with PHCs in oily sludge either
      through oil recovery or sludge disposal, but little attention has been paid to
      handle its various heavy metals. These methods were discussed by dividing them
      into oil recovery and sludge disposal approaches. It was recognized that no
      single specific process can be considered as a panacea since each method is
      associated with different advantages and limitations. Future efforts should focus
      on the improvement of current technologies and the combination of oil recovery
      with sludge disposal in order to comply with both resource reuse recommendations
      and environmental regulations. The comprehensive examination of oily sludge
      treatment methods will help researchers and practitioners to have a good
      understanding of both recent developments and future research directions.

PMID- 23978723
TI  - Blurry as tremor.

PMID- 23978724
TI  - Dopaminergic treatment and nonmotor features of Parkinson disease: the horse
      lives.

PMID- 23978725
TI  - Continuous EEG in therapeutic hypothermia after cardiac arrest: prognostic and
      clinical value.

PMID- 23978720
TI  - Association between elevated coffee consumption and daily chocolate intake with
      normal liver enzymes in HIV-HCV infected individuals: results from the ANRS CO13
      HEPAVIH cohort study.
AB  - BACKGROUND & AIMS: We used longitudinal data from the ANRS CO13 HEPAVIH cohort
      study of HIV-HCV co-infected individuals to investigate whether polyphenol rich
      food intake through coffee and/or daily chocolate consumption could play a role
      in reducing liver enzymes levels. METHODS: Longitudinal data collection included
      self-administered questionnaires and medical data (aspartate aminotransferase
      (AST) and alanine aminotransferase (ALT) liver enzymes). Two analyses were
      performed to assess the association between coffee (>=3 cups a day) and daily
      chocolate intake and abnormal values of AST and ALT (AST or ALT >2.5 * upper
      normal limit (UNL)) (N=990) over time, after adjustment for known correlates.
      Logistic regression models based on generalized estimating equations were used to
      take into account the correlations between repeated measures and estimate
      adjusted odds ratio. RESULTS: After adjustment, patients reporting elevated
      coffee consumption and daily chocolate intake were less likely to present
      abnormal ALT (OR=0.65; p=0.04 and OR=0.57; p=0.04, for coffee and chocolate
      respectively), while only patients reporting elevated coffee consumption were
      less likely to have abnormal AST values (p=0.05). Nevertheless, the combined
      indicator of coffee and chocolate intake was most significantly associated with
      approximately 40% reduced risk of abnormal liver enzymes (p=0.003 for AST;
      p=0.002 for ALT). CONCLUSIONS: Elevated coffee consumption and daily chocolate
      intake appear to be associated with reduced levels of liver enzymes in HIV-HCV co
      infected patients. Further experimental and observational research is needed to
      better understand the role that polyphenol intake or supplementation can play on
      liver disease and liver injury.

PMID- 23978726
TI  - Clinical reasoning: a 35-year-old woman with acute seizures and behavior change.

PMID- 23978727
TI  - Teaching video neuroimages: Hollenhorst plaque.

PMID- 23978728
TI  - Teaching neuroimages: sarcoidosis presenting as longitudinally extensive
      myelitis: excellent response to infliximab.

PMID- 23978729
TI  - The ability to consent to Parkinson disease research.

PMID- 23978730
TI  - Association of altered cardiac autonomic function with psychopathology and
      metabolic profiles in schizophrenia.
AB  - Schizophrenia has been associated with autonomic dysregulation and increased
      cardiovascular co-morbidity. We hypothesised that autonomic dysregulation in
      patients with schizophrenia is associated with psychopathology and metabolic
      profiles. In this study, we aimed to evaluate psychopathology, comprehensive
      metabolic profiles and cardiac autonomic function using heart-rate variability
      (HRV) analysis in patients with schizophrenia. A total of 94 patients with
      schizophrenia and 51 healthy controls were recruited. Each patient underwent a
      physical examination, laboratory tests and rating scale evaluation, and all
      subjects underwent a 1-h electrocardiogram monitoring. Analysis of variance was
      used to compare demographic and HRV variables between control and patient groups.
      We applied multiple regression analysis with backward selection to examine the
      association between HRV indices and demographic, metabolic and psychopathology
      profiles. A decreased HRV was found in patient groups, compared to controls.
      Reduced vagal-related and complexity domain of HRV indices in patient groups were
      correlated with increased body mass indices, diastolic pressure, triglycerides,
      high- and low-density lipoprotein and severity of psychosis mainly in the
      negative symptom domain. This study provides evidence that altered autonomic
      function is associated with both psychopathology and metabolic profiles in
      patients with schizophrenia. These findings may warrant future research in using
      HRV as objective markers to monitor cardiovascular health and the severity of
      psychosis in patients with schizophrenia. 

PMID- 23978731
TI  - Overgenerality memory style for past and future events and emotions related in
      bipolar disorder. What are the links with problem solving and interpersonal
      relationships?
AB  - This study investigated patients with Bipolar Disorder's abilities to generate
      specific past and future events in response to positive and negative cues words
      as well as emotional intensity related to these ones. The relationships between
      the number of generated specific events cognitive functioning, interpersonal
      problems and the ability to problem solving were investigated. Nineteen BD and
      nineteen healthy controls completed a French version of the AMT to evaluate the
      past and future events recall, in function of their valence, and emotions
      related. Furthermore, they completed the Optional Thinking Test, the Inventory of
      Interpersonal Problems and the neuropsychological measures. Compared to healthy
      controls, BD recollected (1) fewer specific past negative events and (2) fewer
      future specific positive and negative events furthermore, (3) they felt more
      emotional intensity related to future events. These results were explained in the
      light of theoretical models. Finally, specific past memories deficits in BD were
      linked with issues in problem solving but not with levels of distress arising
      from interpersonal problems. In view of AM functions in everyday life, all types
      of deficits should be taken into consideration, and AM remediation envisaged. 

PMID- 23978732
TI  - The development of delusion revisited: a transdiagnostic framework.
AB  - This study proposes a transdiagnostic framework for delusion development,
      analysing psychiatric (schizophrenia, bipolar disorder, major depressive
      disorder) and neurological disorders (stroke, and neurodegenerative diseases) in
      which delusions are predominant. Our aim is to identify a transdiagnostic core of
      neural and cognitive alterations associated with delusions across distinct
      clinical disorders. Reviewed empirical evidence suggests delusions are
      associated: on the neural level with changes in the ventromedial prefrontal
      cortex (vmPFC) networks, and on the neuropsychological level with dysfunction in
      the processes (generation of affective value, the construction of internal models
      of the world, and the reflection about Self and/or Other's mental states) that
      these network mediate. The concurrent aberration of all these processes could be
      critical for the clinical transition to a psychotic delusional state. In
      particular, delusions could become clinically manifest when (1) stimuli are
      attributed an aberrant affective salience, that (2) is explained by the patient
      within distorted explanatory internal models that (3) are poorly inhibited by
      cognitive control systems. This framework extends the two-factor account of
      delusion model and suggests that common neural mechanisms for the delusions in
      psychiatric and in neurological disorders. 

PMID- 23978733
TI  - A meaningful life is worth living: meaning in life as a suicide resiliency
      factor.
AB  - Given the high rate of suicide worldwide, it is imperative to find factors that
      can confer resiliency to suicide. The goal of the present study was to examine
      the search for and the presence of meaning in life as possible resilience
      factors. We hypothesized that the presence of, but not the search for, meaning in
      life would predict decreased suicidal ideation over an eight-week time period and
      decreased lifetime odds of a suicide attempt. We also examined a subsidiary
      hypothesis that the presence of, but not the search for, meaning in life would
      mediate the relationship between the two variables associated with the
      interpersonal psychological theory of suicide (i.e., perceived burdensomeness and
      thwarted belongingness) and suicidal ideation. Our results were generally in
      support of our hypothesis: presence of meaning in life predicted decreased
      suicidal ideation over time and lower lifetime odds of a suicide attempt.
      Surprisingly, search for meaning in life also predicted decreased suicidal
      ideation over time. Finally, the search for, but not presence of, meaning in life
      mediated the relationship between the interpersonal psychological theory
      variables and suicidal ideation. These findings suggest that interventions that
      target meaning in life may be useful to attenuate suicide risk in individuals. 

PMID- 23978734
TI  - The impact of self-efficacy, alexithymia and multiple traumas on posttraumatic
      stress disorder and psychiatric co-morbidity following epileptic seizures: a
      moderated mediation analysis.
AB  - This study investigated the incidence of posttraumatic stress disorder (PTSD) and
      psychiatric co-morbidity following epileptic seizure, whether alexithymia
      mediated the relationship between self-efficacy and psychiatric outcomes, and
      whether the mediational effect was moderated by the severity of PTSD from other
      traumas. Seventy-one (M=31, F=40) people with a diagnosis of epilepsy recruited
      from support groups in the United Kingdom completed the Posttraumatic Stress
      Diagnostic Scale, the Hospital Anxiety and Depression Scale, the Toronto
      Alexithymia Scale-20 and the Generalized Self-Efficacy Scale. They were compared
      with 71 people (M=29, F=42) without epilepsy. For people with epilepsy, 51% and
      22% met the diagnostic criteria for post-epileptic seizure PTSD and for PTSD
      following one other traumatic life event respectively. For the control group, 24%
      met the diagnostic criteria for PTSD following other traumatic life events. The
      epilepsy group reported significantly more anxiety and depression than the
      control. Partial least squares (PLS) analysis showed that self-efficacy was
      significantly correlated with alexithymia, post-epileptic seizure PTSD and
      psychiatric co-morbidity. Alexithymia was also significantly correlated with post
      epileptic seizure PTSD and psychiatric co-morbidity. Mediation analyses confirmed
      that alexithymia mediated the path between self-efficacy and post-epileptic
      seizure PTSD and psychiatric co-morbidity. Moderated mediation also confirmed
      that self-efficacy and PTSD from one other trauma moderated the effect of
      alexithymia on outcomes. To conclude, people can develop posttraumatic stress
      disorder symptoms and psychiatric co-morbidity following epileptic seizure. These
      psychiatric outcomes are closely linked with their belief in personal competence
      to deal with stressful situations and regulate their own functioning, to process
      rather than defend against distressing emotions, and with the degree of PTSD from
      other traumas. 

PMID- 23978735
TI  - Learning to see: the moral opportunity of art.

PMID- 23978736
TI  - Characterization of a putative oomycete taurocyamine kinase: Implications for the
      evolution of the phosphagen kinase family.
AB  - Phosphagen kinases (PKs) are known to be distributed throughout the animal
      kingdom, but have recently been discovered in some protozoan and bacterial
      species. Within animal species, these enzymes play a critical role in energy
      homeostasis by catalyzing the reversible transfer of a high-energy phosphoryl
      group from Mg?ATP to an acceptor molecule containing a guanidinium group. In this
      work, a putative PK gene was identified in the oomycete Phytophthora sojae that
      was predicted, based on sequence homology, to encode a multimeric
      hypotaurocyamine kinase. The recombinant P. sojae enzyme was purified and shown
      to catalyze taurocyamine phosphorylation efficiently (kcat/KM (taurocyamine) = 2
      * 10(5) M(-1) s(-1)) and glycocyamine phosphorylation only weakly (kcat/KM
      (glycocyamine) = 2 * 10(2) M(-1) s(-1)), but lacked any observable kinase
      activity with the more ubiquitous guanidinium substrates, creatine or arginine.
      Additionally, the enzyme was observed to be dimeric but lacked cooperativity
      between the subunits in forming a transition state analog complex. These results
      suggest that protozoan PKs may exhibit more diversity in substrate specificity
      than was previously thought.

PMID- 23978737
TI  - Ruthenium(II) carbonyl complexes bearing quinoline-based NNO tridentate ligands
      as catalyst for one-pot conversion of aldehydes to amides and o-allylation of
      phenols.
AB  - Six new octahedral ruthenium(II) carbonyl complexes having the general molecular
      formula [RuCl(CO)(B)L(1-2)] (B = PPh3, AsPh3 or py; L(1-2) = quinoline based NNO
      ligand) were synthesized. The quinoline based ligands behave as monoanionic
      tridentate donor and coordinated to ruthenium via ketoenolate oxygen, azomethine
      nitrogen and quinoline nitrogen. The composition of the complexes has been
      established by elemental analysis and spectral methods (FT-IR, electronic, (1)H
      NMR, (13)C NMR, (31)P NMR and ESI-Mass). The complexes were used as efficient
      catalysts for one-pot conversion of various aldehydes to their corresponding
      primary amides in presence of NH2OH . HCl and NaHCO3. The effect of catalyst
      loading and reaction temperature on catalytic activity of the ruthenium(II)
      carbonyl complexes were also investigated. The synthesized complexes also possess
      good catalytic activity for the o-allylation of phenols in the presence of K2CO3
      under mild conditions. The complexes afforded branched allyl aryl ethers
      according to a regioselective reaction.

PMID- 23978738
TI  - FT-IR, FT-Raman spectra and other molecular properties of 3,5
      dichlorobenzonitrile: a DFT study.
AB  - The IR and Raman spectra of 3,5-dichlorobenzonitrile (3,5-DCBN) molecule were
      recorded at room temperature and then the assignment of the observed fundamental
      bands were achieved by the aid of the theoretical vibrational spectral data
      obtained from a quantum chemical study carried out for the free molecule case. In
      the calculations performed to determine the molecular geometry, vibrational
      spectral data and thermodynamic parameters, Moller-Plesset second order
      perturbation theory (MP2) and hybrid Density Functional Theory (DFT) types of
      electronic structure methods, B3LYP and B3PW91, were used. The overestimations of
      the calculated harmonic wavenumbers were efficiently corrected by the aid of a
      specific scaling procedure. This empirical scaling process significantly
      increased the reliability of our assignments and analyses on the observed bands
      due to different vibrational normal modes of the molecule. For the majority of
      the normal modes, the deviations between the corresponding experimental and
      scaled theoretical wavenumbers have located in the expected range. A correct
      characterization of the normal modes is of vital importance in the assignment of
      the observed bands, and this was successfully done by the aid of the Potential
      Energy Distributions (PEDs) separately calculated for each normal mode of 3,5
      DCBN. 

PMID- 23978739
TI  - Combination of best promoter and micellar catalyst for more than kilo-fold rate
      acceleration in favor of chromic acid oxidation of D-galactose to D-galactonic
      acid in aqueous media at room temperature.
AB  - Picolinic acid, 2,2'-bipyridine and 1,10-phenanthroline promoted Cr(VI) oxidation
      of D-galactose to D-galactonic acid in three representative aqueous micellar
      media has been studied. The anionic surfactant (SDS) accelerated the rate of
      reaction while the cationic surfactant (CPC) and neutral surfactant (TX-100)
      retarded the reaction rate. Combination of bipy and SDS is the best choice for
      chromic acid oxidation of D-galactose to D-galactonic acid in aqueous media
      although 1,10-phenanthroline is best promoter in absence of micellar catalyst.

PMID- 23978740
TI  - Surface enhanced Raman scattering, electronic spectrum, natural bond orbital, and
      Mulliken charge distribution in the normal modes of diethyldithiocarbamate copper
      (II) complex, [Cu(DDTC)2].
AB  - Surface-enhanced Raman scattering (SERS) was used to study the interactions of
      the normal modes of the diethyldithiocarbamate copper (II) complex, [Cu(DDTC)2]
      on nano-structured mixture silver-gold surfaces and on silver surfaces. The
      electronic spectrum of this complex was measured and the charge transfer bands
      were assigned through the TD-PBE1PBE procedure. Natural bond orbital (NBO) were
      also carried out to study the Cu(II) hybridation leading to the square planar
      geometry of the framework of the [Cu(DDTC)2] complex, and to study which are the
      donor NBO and the acceptor NBO in meaningful charge transfer through the Second
      Order Perturbation Theory Analysis of the Fox Matrix in NBO basis. To see the
      electronic dispersion, the Mulliken electronic charges (MAC) were calculated for
      each normal mode and correlated with the SERS effect. Full assignment of the SERS
      spectra was also supported by carefully analysis of the distorted geometries
      generated by the normal modes. 

PMID- 23978741
TI  - Quantum chemical density functional theory studies on the molecular structure and
      vibrational spectra of Gallic acid imprinted polymers.
AB  - Gallic acid (GA) is known by its antioxidant, anticarcinogenic properties and
      scavenger activity against several types of harmful free radicals. Molecularly
      imprinted polymers (MIPs) are used in separation of a pure compound from complex
      matrices. A stable template-monomer complex generates the MIPs with the highest
      affinity and selectivity for the template. The quantum chemical computations
      based on density functional theory (DFT) was used on the template Gallic acid
      (GA), monomer acrylic acid (AA) and GA-AA complex to study the nature of
      interactions involved in the GA-AA complex. B3LYP/6-31+G(2d,2p) model chemistry
      was used to optimize their structures and frequency calculations. The effect of
      porogen acetonitrile (ACN) on complex formation was included by using polarizable
      continuum model (PCM). The results demonstrated the formation of a stable GA-AA
      complex through the intermolecular hydrogen bonding between carboxylic acid
      groups of GA and AA. The Mulliken atomic charge analysis and simulated
      vibrational spectra also supported the stable hydrogen bonding interaction
      between the carboxylic acid groups of GA and AA with minimal interference of
      porogen ACN. Further, simulations on GA-AA mole ratio revealed that 1:4 GA-AA was
      optimum for synthesis of MIP for GA. 

PMID- 23978742
TI  - Normal coordinate analysis and Nonlinear Optical Response of cross-conjugated
      system 4,4-Dimethyl Benzophenone.
AB  - FT-Raman and IR spectra of the nonlinear optical active crystal, 4,4-Dimethyl
      Benzophenone (4DMBP) have been recorded and analyzed The equilibrium geometry,
      harmonic vibrational wavenumbers of 4DMBP investigated with the help of density
      functional theory (DFT) method. The assignments of the vibrational spectra have
      been carried out with the help of normal coordinate analysis (NCA) following the
      scaled quantum mechanical force field methodology (SQMFF). The calculated
      hyperpolarizability value shows the nonlinear optical activity of the molecule.
      The value of HOMO-LUMO energy, Mulliken and the natural charges are calculated
      and analyzed. The Natural bond orbital analysis confirms the occurrence of
      intramolecular charge transfer interaction. 

PMID- 23978743
TI  - Experimental and theoretical study of the vibrational spectra of 12-thiacrown-4
      and 18-thiacrown-6, evaluation of the performance of the different anharmonic
      force fields compared to the scaled quantum mechanical force fields.
AB  - We report, to the best of our knowledge, for the first time the vibrational, IR
      and Raman, spectra of 12-thiacrown-4 (12t4) and 18-thiacrown-6 (18t6). To predict
      in what conformation 12t4 and 18t6 exist, for the vibrational analysis of both
      molecules and to assess the performance of the different computational methods
      for the accurate prediction of the vibrational frequencies of relatively large
      molecules, the computations were done using the harmonic and anharmonic force
      fields using the 6-31G* and 6-311G** basis sets. The computations were performed
      at the HF, B3LYP, CAM-B3LYP, BLYP, BP86, G96LYP, PBE1PBE, TPSSH and MP2 levels.
      Comparison was made between the calculated and experimental vibrational
      frequencies as indicated by the root-mean-square (rms) deviations, using either
      the unscaled and scaled harmonic vibrational frequencies and, unscaled,
      anharmonic vibrational frequencies. For the harmonic vibrational frequencies two
      scaling schemes were used. One uses one-scale-factor (1SF) scaling and the other
      uses 8SF scaling. In terms of the vibrational analysis of 12t4 and 18t6, the
      report confirms the solid state X-ray structure of D4 of 12t4 and C2 of 18t6. It
      is concluded that a lower rms deviation is obtained using 1SF scaled harmonic
      vibrational frequencies at even the HF/6-31G* level than using anharmonic
      vibrational frequencies at the MP2/6-311G** level. The CAM-B3LYP method showed
      some improvement over the traditional B3LYP method.

PMID- 23978744
TI  - A novel luminol chemiluminescent method catalyzed by silver/gold alloy
      nanoparticles for determination of anticancer drug flutamide.
AB  - It was found that silver/gold alloy nanoparticles enhance the chemiluminescence
      (CL) of the luminol-H2O2 system in alkaline solution. The studies of UV-Vis
      spectra, CL spectra, effects of concentrations luminol, hydrogen peroxide and
      silver/gold alloy nanoparticles solutions were carried out to explore the CL
      enhancement mechanism. Flutamide was found to quench the CL signals of the
      luminol-H2O2 reaction catalyzed by silver/gold alloy nanoparticles, which made it
      applicable for the determination of flutamide. Under the optimum conditions, the
      CL intensity is proportional to the concentration of the flutamide in solution
      over the range 5.0 * 10(-7) to 1.0 * 10(-4)mol L(-1). Detection limit was
      obtained 1.2 * 10(-8)mol L(-1)and the relative standard deviation (RSD) gamma5%.
      This work is introduced as a new method for the determination of flutamide in
      commercial tablets. Box-Behnken experimental design is applied to investigate and
      validate the CL measurement parameters.

PMID- 23978745
TI  - Crystallographic structure and quantum chemical computations of 1-(3,4
      dimethylphenyl)-3-phenyl-5-(4-methoxyphenyl)-2-pyrazoline.
AB  - In this study the experimental crystallographic structure and the calculated
      optimized geometric parameters, vibrational wavenumbers, (1)H NMR and (13)C NMR
      chemical shift values, electronic absorption maximum wavelength values, HOMO-LUMO
      analysis, and molecular electrostatic potential (MEP) of 1-(3,4-dimethylphenyl)-3
      phenyl-5-(4-methoxyphenyl)-2-pyrazoline (in abbreviated 1h), molecule,
      (C24H24N2O), by using density functional theory (DFT/B3LYP) method with 6
      311++G(d,p) basis set in the ground state have been reported for the first time.
      Furthermore the IR and Raman spectra of title molecule were simulated by using
      calculated vibrational results. Geometric parameters (bond lengths and bond
      angles) vibrational wavenumbers and (13)C &(1)H NMR chemical shift values for the
      mentioned compound calculated at B3LYP/6-311++G(d,p) level are in good agreement
      with the experimental data. 

PMID- 23978746
TI  - Synthesis, characterization and optical properties of gelatin doped with silver
      nanoparticles.
AB  - In this study, silver nanoparticles were synthesized by chemical reduction of
      silver salt (AgNO3) solution. Formation of nanoparticles was confirmed by UV
      visible spectrometry. The surface plasmon resonance peak is located at 430 nm.
      Doping of silver nanoparticles (Ag NPs) with gelatin biopolymer was studied. The
      silver content in the polymer matrix was in the range of 0.4-1 wt%. The formation
      of nanoparticles disappeared for silver content higher than 1 wt%. The morphology
      and interaction of gelatin doped with Ag NPs was examined by transmission
      electron microscopy and FTIR spectroscopy. The content of Ag NPs has a pronounced
      effect on optical and structural properties of gelatin. Optical parameters such
      as refractive index, complex dielectric constant were calculated. The dispersion
      of the refractive index was discussed in terms of the single--oscillator Wemple
      DiDomenico model. Color properties of the prepared samples were discussed in the
      framework of CIE L(*)u(*)v(*) color space.

PMID- 23978747
TI  - Intramolecular interactions in ortho-methoxyalkylphenylboronic acids and their
      catechol esters.
AB  - Catechol esters of ortho-methoxyalkylphenylboronic acids have been synthesized
      and characterized by (17)O NMR spectroscopy. The results were compared with the
      data for the parent acids. The influence of intramolecular and intermolecular
      hydrogen bonds on the properties of the boronic acids has been discussed. The
      (17)O NMR data for the boronic esters proved that there are no O -> B
      interactions in the investigated compounds. This fact is connected with weak
      Lewis acidity of the parent acids and their low sugars' receptors activity.
      Crystal structure of ortho-methoxyphenylboronic acid catechol ester was
      determined.

PMID- 23978748
TI  - FT-IR and FT-Raman, NMR and UV spectroscopic investigation and hybrid
      computational (HF and DFT) analysis on the molecular structure of mesitylene.
AB  - The spectroscopic properties of mesitylene were investigated by FT-IR, FT-Raman,
      UV, (1)H and (13)C NMR techniques. The geometrical parameters and energies have
      been obtained from density functional theory (DFT) B3LYP method and Hartree-Fock
      (HF) method with 6-311++G(d,p) and 6-311G(d,p) basis sets calculations. The
      geometry of the molecule was fully optimized, vibrational spectra were calculated
      and fundamental vibrations were assigned on the basis of the total energy
      distribution (TED) of the vibrational modes, calculated with scaled quantum
      mechanics (SQM) method and PQS program. Total and partial density of state (TDOS
      and PDOS) and also overlap population density of state (OPDOS) diagrams analysis
      were presented. (13)C and (1)H NMR chemical shifts were calculated by using the
      gauge-invariant atomic orbital (GIAO) method. The electronic properties, such as
      excitation energies, oscillator strength, wavelengths, HOMO and LUMO energies,
      were performed by time-dependent density functional theory (TD-DFT) results
      complements with the experimental findings. The results of the calculations were
      applied to simulate spectra of the title compound, which show excellent agreement
      with observed spectra. Besides, frontier molecular orbitals (FMO), molecular
      electrostatic potential (MEP) and thermodynamic properties were performed.
      Reduced density gradient (RDG) of the mesitylene was also given to investigate
      interactions of the molecule. 

PMID- 23978749
TI  - Silica-based monolithic capillary columns modified by liposomes for
      characterization of analyte-liposome interactions by capillary liquid
      chromatography.
AB  - This study introduces a silica-based monolith in a capillary format (0.1 mm * 100
      mm) as a support for immobilization of liposomes and its characterization in
      immobilized liposome chromatography. Silica-based monolithic capillary columns
      prepared by acidic hydrolysis of tetramethoxysilane in the presence of
      polyethylene glycol and urea were modified by (3-aminopropyl)trimethoxysilane,
      whereby amino groups were introduced to the monolithic surface. These groups
      undergo reaction with glutaraldehyde to form an iminoaldehyde, allowing covalent
      binding of pre-formed liposomes containing primary amino groups. Two types of
      phospholipid vesicles were used for column modification; these were 2-oleoyl-1
      palmitoyl-sn-glycero-3-phosphatidyl choline with and without 1,2-diacyl-sn
      glycero-3-phospho-L-serine. The prepared columns were evaluated under isocratic
      separation conditions employing 20mM phosphate buffer at pH 7.4 as a mobile phase
      and a set of unrelated drugs as model analytes. The liposome layer on the
      synthesized columns significantly changed the column selectivity compared to the
      aminopropylsilylated monolithic stationary phase. Monolithic columns modified by
      liposomes were stable under the separation conditions, which proved the
      applicability of the suggested preparation procedure for the synthesis of
      capillary columns dedicated to study analyte-liposome interactions. The column
      efficiency originating from the silica monolith was preserved and reached, e.g.,
      more than 120,000 theoretical plates/m for caffeine as a solute.

PMID- 23978768
TI  - Community-analyzer: a platform for visualizing and comparing microbial community
      structure across microbiomes.
AB  - A key goal in comparative metagenomics is to identify microbial group(s) which
      are responsible for conferring specific characteristics to a given environment.
      These characteristics are the result of the inter-microbial interactions between
      the resident microbial groups. We present a new GUI-based comparative metagenomic
      analysis application called Community-Analyzer which implements a correlation
      based graph layout algorithm that not only facilitates a quick visualization of
      the differences in the analyzed microbial communities (in terms of their
      taxonomic composition), but also provides insights into the inherent inter
      microbial interactions occurring therein. Notably, this layout algorithm also
      enables grouping of the metagenomes based on the probable inter-microbial
      interaction patterns rather than simply comparing abundance values of various
      taxonomic groups. In addition, the tool implements several interactive GUI-based
      functionalities that enable users to perform standard comparative analyses across
      microbiomes. For academic and non-profit users, the Community-Analyzer is
      currently available for download from:
      http://metagenomics.atc.tcs.com/Community_Analyzer/. 

PMID- 23978769
TI  - Carotid artery atherosclerosis is correlated with cognitive impairment in an
      elderly urban Chinese non-stroke population.
AB  - Carotid artery atherosclerosis may cause increased intima-media thickness (IMT),
      plaque formation, and vessel stenosis or occlusion. However, the association
      between carotid artery atherosclerosis and cognitive impairment remains
      uncertain. This study explored the effects of IMT and carotid artery stenosis on
      cognitive function in an elderly Chinese non-stroke population. A total of 2015
      patients were recruited. The IMT of carotid arteries and the presence of plaques
      and stenosis in carotid arteries were assessed with B-mode ultrasound
      examination. Cognitive performance was evaluated with neuropsychological tests.
      The cross-sectional relationships between cognitive performance and carotid wall
      characteristics were analyzed. Carotid artery atherosclerosis (IMT>1.0) and
      stenosis were found in 86% and 51% of patients, respectively. Cognitive
      impairment was found in 356 (17.7%) patients. After adjustment for possible
      confounders, IMT (odds ratio [OR]=1.96; 95% confidence interval [CI] 1.23-3.16)
      and hyperdense plaque (OR=4.72; 95% CI 2.56-11.2) were associated with poor
      cognitive performance. Patients with severe (>=70%) carotid artery stenosis had a
      lower Mini-Mental State Examination score compared with the mild to modest (40
      70%) carotid artery stenosis group. Cognitive performance differed between
      patients with left and right carotid artery stenosis, but no differences were
      observed between patients with severe left and right carotid artery stenosis.
      This study indicates that carotid artery atherosclerosis is correlated with
      cognitive impairment in the elderly Chinese population. A larger sample size
      across multiple centers and a longitudinal study are required to further explore
      the impact of carotid artery atherosclerosis on cognition in the elderly
      population.

PMID- 23978770
TI  - HPLC and HPTLC methods by design for quantitative characterization and in vitro
      anti-oxidant activity of polyherbal formulation containing Rheum emodi.
AB  - Safoof-e-Pathar phori (SPP) is a traditional polyherbal formulation and has been
      used since long time for its anti-urolithiatic activity. It contains three plant
      constituents Didymocarpous pedicellata, Dolichous biflorus and Rheum emodi.
      Emodin and chrysophanic acid were selected as chemical markers for SPP and
      quantified using simultaneous HPTLC and RP-HPLC methods in R. emodi and in SPP.
      The simultaneous methods were found linear r(2) = 0.991 in a wide range (10-800
      ng spot(-1) with HPTLC, 5-500 ug mL(-1) with HPLC) precise, accurate and robust
      for both the drugs. Anti-oxidant activity of SPP, R. emodi as well as standard
      emodin and chrysophanic acid were determined by using DPPH (2,2-diphenyl-1-picryl
      hydrazyl radical), which showed better activity of R. emodi (IC50 = 12.27)
      extract when compared with SPP (IC50 = 32.99) and standard drugs (IC50 = 66.81).
      The robustness of methods were proved by applying the Box-Behnken response
      surface design software and other validation parameters evaluated were
      satisfactorily met; hence, the developed method found suitable for application in
      the quality control of several formulations containing emodin and chrysophanic
      acid. 

PMID- 23978771
TI  - Micellar electrokinetic chromatographic determination of triazine herbicides in
      water samples.
AB  - Dispersive liquid-liquid microextraction combined with online sweeping
      preconcentration in micellar electrokinetic chromatography was developed for the
      simultaneous determination of five triazine herbicides (atrazine, simazine,
      propazine, prometon and simetryn) in water samples. Several experimental
      parameters affecting the extraction efficiencies such as the type and volume of
      both the extraction and dispersive solvents, the addition of salt to sample
      solution, the extraction time and the pH of the sample solution were
      investigated. Under optimum conditions, the linearity of the method was good in
      the range from 0.33 to 20 ng mL(-1) for simazine, propazine, atrazine and
      simetryn, and from 0.17 to 20 ng mL(-1) for prometon, respectively. The
      sensitivity enrichment factors were in the range from 1750 to 2100, depending on
      the compound. The limit of detection (S/N = 3) ranged from 0.05 to 0.10 ng mL(
      1). The developed method was successfully applied to the analysis of the five
      triazines in river, ground and well waters. 

PMID- 23978772
TI  - An empirically based simulation of group foraging in the harvesting ant, Messor
      pergandei.
AB  - We present an empirically based group model of foraging interactions in Messor
      pergandei, the Sonoran desert harvesting ant. M. pergandei colonies send out
      daily foraging columns consisting of tens of thousands of individual ants. Each
      day, the directions of the columns may change depending on the resource
      availability and the neighbor interactions. If neighboring columns meet, ants
      fight, and subsequent foraging is suppressed. M. pergandei colonies face a
      general problem which is present in many systems: dynamic spatial partitioning in
      a constantly changing environment, while simultaneously minimizing negative
      competitive interactions with multiple neighbors. Our simulation model of a
      population of column foragers is spatially explicit and includes neighbor
      interactions. We study how different behavioral strategies influence resource
      exploitation and space use for different nest distributions and densities. Column
      foraging in M. pergandei is adapted to the spatial and temporal properties of
      their natural habitat. Resource and space use is maximized both at the colony and
      the population level by a model with a behavioral strategy including learning and
      fast forgetting rates. 

PMID- 23978773
TI  - An expanded approach to batterer intervention programs incorporating neuroscience
      research.
AB  - Batterer Intervention Programs have been critiqued for failing to incorporate
      treatment strategies that are supported by neurobiology research. This article
      reviews findings that have informed the treatment of disorders that are strongly
      represented among perpetrators of intimate violence, such as addiction,
      posttraumatic stress disorder, mood, anxiety, and personality disorders. The
      article argues for an expanded perspective that recognizes the relationships
      among childhood trauma, emotional regulation impairment, and intimate partner
      violence. Recommendations and ways to draw on emerging knowledge to invigorate
      existing programs are provided. 

PMID- 23978774
TI  - Definition of psychotic disorders in the DSM-5 too radical, too conservative, or
      just right!

PMID- 23978775
TI  - Neurocognition, functional capacity, and functional outcomes: the cost of
      inexperience.
AB  - BACKGROUND: Neurocognitive impairments are the strongest predictor of functional
      deficits in schizophrenia, but adaptive (i.e., functional) capacity, typically
      measured with performance-based assessments, yields an objective index of current
      abilities, whereas real-world functional performance relies on observations of
      community activity. However, limited experiences in the community may limit the
      acquisition, retention, or expression of these skills. METHODS: We examined the
      frequency of engagement in behaviors that are assessed in the current "gold
      standard" in person functional capacity assessment. The UCSD Performance-Based
      Skills Assessment (i.e., UPSA) examines skills associated with recreational
      engagement, handling money, scheduling appointments, and navigating public
      transportation. We used neurocognition, experience, and UPSA performance as
      predictors of the relationships among cognition and real-world functioning
      variables. RESULTS: Neurocognition was a significant correlate of UPSA scores
      regardless of whether it was forced into the model before or after prior
      experience, whereas experience was only a significant predictor of UPSA scores
      when entered before neurocognition. Further, functional capacity, neurocognition,
      and experience were significant predictors of real-world outcomes and experience
      remained a significant predictor regardless of the order it was entered into the
      model. CONCLUSIONS: The amount of current experience with functional tasks is not
      a rate-limiter of the relationships between neurocognition and functional
      capacity but does account for some previously unexplained variance in the
      functional capacity-everyday functioning relationship. These findings underscore
      the importance of neurocognitive deficits as they relate to functional capacity
      in schizophrenia, and suggest an incremental functional cost of limited
      experience with independent living.

PMID- 23978776
TI  - Are there clinically useful predictors and early warning signs for pending
      relapse?
AB  - OBJECTIVE: Despite the availability of effective long-term treatment strategies
      in schizophrenia, relapse is still common. Relapse prevention is one of the major
      treatment objectives, because relapse represents burden and costs for patients,
      their environment, and society and seems to increase illness progression at the
      biological level. Valid predictors for relapse are urgently needed to enable more
      individualized recommendations and treatment decisions to be made. METHODS:
      Mainly recent evidence regarding predictors and early warning signs of relapse in
      schizophrenia was reviewed. In addition, data from the first-episode (long-term)
      study (FES; Gaebel et al., 2007, 2011) performed within the German Research
      Network on Schizophrenia were analyzed. RESULTS: On the basis of FES data,
      premorbid adjustment, residual symptoms and some side effects are significant
      predictors. Although a broad spectrum of potential parameters has been
      investigated in several other studies, only a few and rather general valid
      predictors were identified consistently. Data of the FES also indicated that
      predictive power could be enhanced by considering interacting conjunctions, as
      suggested by the Vulnerability-Stress-Coping model. Prospective studies, however,
      are rare. In addition, prodromal symptoms as course-related characteristics
      likewise investigated in the FES add substantially to early recognition of
      relapse and may serve as early warning signs, but prognosis nevertheless remains
      a challenge. CONCLUSIONS: Comprehensive and well-designed studies are needed to
      identify and confirm valid predictors for relapse in schizophrenia. In this
      respect, broadly accepted and specifically defined criteria for relapse would
      greatly facilitate comparison of results across studies.

PMID- 23978777
TI  - Connecting in distance mentoring: communication practices that work.
AB  - BACKGROUND: As nursing and healthcare become more global, supported by
      technology, the opportunities for distance mentoring increase. Mentorship is
      critical to nurse educator recruitment and retention. STUDY OBJECTIVE: The
      purpose of this study was to identify communication practices of nurse educators
      involved in mentoring at a distance. DESIGN/SETTINGS: A qualitative design,
      utilizing in-person or telephone interviews was used. Participants were twenty
      three proteges or mentors who were part of a yearlong distance mentoring program.
      ANALYSIS METHOD: An iterative process of hermeneutic analysis identified three
      themes; this paper focuses on the theme of connectedness. RESULTS: Participant
      narratives illuminate practices of connecting at a distance: meeting face-to
      face, sharing personal information, experiencing reciprocity, journaling, being
      vulnerable, establishing one's presence, and appreciating different perspectives.
      CONCLUSION: Distance does not appear to limit the connecting potential leading to
      a meaningful mentoring relationship; rather, it offers possibilities that local
      mentoring relationships may not. Nurse educators in under-resourced countries,
      those in small programs without a cadre of senior faculty, and students in
      distance programs are among those who stand to benefit from distance mentoring
      relationships.

PMID- 23978778
TI  - Key components of an effective mentoring relationship: a qualitative study.
AB  - BACKGROUND: Despite the recognized importance of mentoring, little is known about
      specific mentoring behaviors that result in positive outcomes. OBJECTIVE: To
      identify key components of an effective mentoring relationship identified by
      proteges-mentor dyads in an academic setting. METHODS: In this qualitative study,
      purposive sampling resulted in geographic diversity and representation of a range
      of academic disciplines. Participants were from 12 universities in three regions
      of the U.S. (South, n=5; Northeast, n=4; Midwest, n=2) and Puerto Rico (n=1).
      Academic disciplines included natural sciences (51%), nursing/health sciences
      (31%), engineering (8%), and technology (1%). Twelve workshops using the
      Technology of Participation method were held with 117 mentor-protege dyads.
      Consensus was reached regarding the key components of an effective mentoring
      relationship. RESULTS: Conventional content analysis, in which coding categories
      were informed by the literature and derived directly from the data, was employed.
      Eight themes described key components of an effective mentoring relationship: (1)
      open communication and accessibility; (2) goals and challenges; (3) passion and
      inspiration; (4) caring personal relationship; (5) mutual respect and trust; (6)
      exchange of knowledge; (7) independence and collaboration; and (8) role modeling.
      Described within each theme are specific mentor-protege behaviors and
      interactions, identified needs of both protege and mentor in the relationship,
      and desirable personal qualities of mentor and protege. CONCLUSIONS: Findings can
      inform a dialog between existing nurse mentor-protege dyads as well as student
      nurses and faculty members considering a mentoring relationship. Nurse educators
      can evaluate and modify their mentoring behaviors as needed, thereby
      strengthening the mentor-protege relationship to ensure positive outcomes of the
      learning process.

PMID- 23978779
TI  - Educational competencies and technologies for disaster preparedness in
      undergraduate nursing education: an integrative review.
AB  - OBJECTIVES: This integrative review of literature was conducted to determine (1)
      what are the suitable disaster preparedness competencies for undergraduate
      nursing curriculum? and (2) what are the suitable methods of instruction to
      deliver disaster preparedness content? DATA SOURCES AND REVIEW METHOD: A
      literature search was conducted on three major electronic databases: Ovid
      MEDLINE, PubMed and the Cumulative Index of Nursing and Allied Health Literature
      (CINAHL) using the keywords; Disaster Preparedness, Disaster and nursing
      education; disaster response and nursing education. Limiters used were published
      within the last 10 years and in nursing field. Out of the 190 articles retrieved,
      eight were research articles that met the inclusion criteria. These articles were
      carefully reviewed and the results are summarized in two sections to answer the
      research questions. RESULTS AND FINDINGS: There was no uniformity of intended
      competencies among the studies, though all studies used resources from reputed
      national and international organizations. All the studies reviewed adhered to a
      systematic approach in delivering content and used eclectic methods including
      multiple technologies to enhance the educational outcomes. Most of the studies
      had incorporated simulation in different ways involving low to high fidelity
      simulators, virtual simulation and live actors. Content and length of the
      programs were greatly varied but stayed focused on the general principles of
      disaster management and appropriate for the level of the students within the
      programs. DISCUSSION AND CONCLUSION: More rigorous research is needed in this
      area since all published articles had deficiencies in the methodologies,
      especially in data collection and analysis. Disaster preparedness education was
      found to be a suitable activity for interprofessional education.

PMID- 23978780
TI  - Relationship between time of day physical exercise and the reduced risk of
      coronary artery disease in a Chinese population.
AB  - PURPOSE: Exercise leads to a lower risk of coronary artery disease (CAD).
      However, whether time of day physical exercise has effects on CAD is still
      unclear. The present study is to investigate the relationship between time of day
      physical exercise and angiography determined CAD in a Chinese population.
      SUBJECTS: A total of 1,129 consecutive participants who underwent coronary
      angiography for the first time were enrolled in our study. Participants were
      divided into non-CAD group and CAD group according to the result of coronary
      angiography. We used a predesigned questionnaire-the work-related activity,
      leisure-time activity, and physical exercise information were recorded in the
      form of self-reporting. RESULTS: Doing physical exercise was associated with a
      reduced risk of CAD, after adjusting the established and potential confounders,
      with an adjusted odds ratio (OR) of 0.48 (95% CI, 0.35-0.67) compared with those
      who did not any physical exercise. Moreover, the risk of CAD could linearly
      decrease with increase of intensity, duration and frequency of exercise. Further
      stratification analysis revealed that the protective effects of exercise were
      more significant in the afternoon and evening group than in the morning and
      forenoon group. The adjusted ORs of doing physical exercise in morning, forenoon,
      afternoon, and evening groups were 0.53 (0.36-0.78), 0.51(0.27-0.96), 0.46(0.25
      0.85), 0.43(0.28-0.66), respectively, compared with nonexerciser (p < .05).
      CONCLUSIONS: Doing physical exercise can decrease the risk of CAD, and exercising
      in the afternoon or evening may have more significant effects on the prevention
      of CAD than in other time of day.

PMID- 23978781
TI  - Biological therapy for systemic vasculitis: a systematic review.
AB  - OBJECTIVE: Relapses and failure are frequent in systemic vasculitis (SV)
      patients. Biological agents have been prescribed as rescue therapies. The aim of
      this systematic review is to analyze the current evidence on the therapeutic use
      of biological agents for SV. METHODS: MEDLINE, EMBASE, the Cochrane Database of
      Systematic Reviews, and the Cochrane Central Register of Controlled Trials were
      searched up to the end of April 2013. Systematic reviews and meta-analysis,
      clinical trials, cohort studies, and case series with >3 patients were included.
      Independent article review and study quality assessment was done by 2
      investigators with consensus resolution of discrepancies. RESULTS: Of 3447
      citations, abstracts, and hand-searched studies screened, 90 were included. Most
      of the studies included ANCA-associated vasculitis (AAV) patients and only a few
      included large vessel vasculitis (LVV) patients. Rituximab was the most used
      agent, having demonstrated efficacy for remission induction in patients with AAV.
      A number of studies used different anti-TNFalpha agents with contrasting results.
      A few uncontrolled studies on the use of abatacept, alemtuzumab, mepolizumab, and
      tocilizumab were found. CONCLUSION: Current evidence on the use of biological
      therapies for SV is mainly based on uncontrolled, observational data. Rituximab
      is not inferior to cyclophosphamide for remission induction in AAV and might be
      superior in relapsing disease. Infliximab and adalimumab are effective as steroid
      sparing agents. Etanercept is not effective to maintain remission in patients
      with granulomatosis with polyangiitis, and serious adverse events have been
      reported. For LVV, both infliximab and etanercept had a role as steroid-sparing
      agents, and tocilizumab might be effective also for remission induction in LVV.

PMID- 23978782
TI  - Subjective visibility depends on level of processing.
AB  - Is visual awareness graded or binary? Experimental work has provided support for
      both possibilities, leading to two coexisting but contradictory theoretical
      accounts. Here we propose a promising candidate factor through which to integrate
      both accounts: the depth of stimulus processing required by the task. We compared
      color identification (a low-level task) with numerical judgements (a high-level
      task) performed on the very same colored number stimuli. Psychophysical curves
      were analyzed for both objective discrimination performance and subjective
      visibility ratings on a trial-by trial basis. We observed a graded relationship
      between stimulus duration and visibility in the low-level task, but a more non
      linear relationship in the high-level task. Both patterns of results have
      previously been consistently associated with the graded and the dichotomous
      account, respectively. Follow-up experiments that manipulate the level of
      processing can further unify previously inconsistent results, thus integrating
      two major theories of visual awareness. 

PMID- 23978786
TI  - Experimental model of trigger finger through A1 pulley constriction in a human
      cadaveric hand: a pilot study.
AB  - PURPOSE: Although it can be reasonably assumed that trigger digits occur as the
      result of a size mismatch in the pulley-tendon system, it is unclear whether
      locking, histological changes, and nodule formation occur owing to an
      intrinsically too small pulley or an enlarged digital flexor tendon. Our purposes
      in this feasibility study were to (1) create a model of trigger digit by pulley
      constriction in nonpreserved human tissue, (2) measure the change in work of
      flexion as the force of pulley constriction increased, (3) compare the work of
      flexion between nontriggering and triggering conditions, and (4) determine
      whether triggering can occur at the A2, A3, and A4 pulleys under similar
      conditions. METHODS: Using a tensiometer, we studied the work of flexion in 4
      fingers (thumb, index, middle, and ring) in a human cadaveric hand. The load of
      flexion was measured as the A1 to A4 pulleys were incrementally constricted in
      order to induce triggering. Work of flexion was analyzed for differences among
      trial conditions. RESULTS: Triggering was successfully induced in all 4 digits
      through constriction of the A1 pulley. No triggering occurred in any of the A2,
      A3, or A4 pulley systems in this model. CONCLUSIONS: We successfully created a
      trigger model in a human cadaveric hand. Our results demonstrate that the A1
      pulley can cause triggering from manual constriction of the pulley alone.
      CLINICAL RELEVANCE: A trigger model such as this may allow investigations of
      pathophysiology, and this may result in novel treatment strategies and
      modalities.

PMID- 23978787
TI  - Biomechanical analysis of the distal metaphyseal ulnar shortening osteotomy.
AB  - PURPOSE: To investigate the effect of a closing wedge osteotomy at the distal
      ulnar metaphysis on unloading the ulnar side of the wrist. METHODS: Seven fresh
      frozen cadaver arms mounted in a wrist simulator were used for the analysis. A 6
      degrees-of-freedom load cell was mounted on the distal radius and another on the
      distal ulna. Radioulnar carpal joint forces and transverse distal radioulnar
      joint (DRUJ) load were measured at static wrist positions and during dynamic
      wrist motions before and after the distal metaphyseal ulnar shortening osteotomy
      (DMUSO) was performed. RESULTS: At each static position, significant decreases in
      ulnar load were noted after DMUSO. In addition, mean and maximum loads decreased
      for each dynamic wrist motion. There were no statistically significant
      differences in transverse forces across the DRUJ after DMUSO. CONCLUSION: This
      study showed that DMUSO is an effective way to decrease the load across the
      ulnocarpal joint. The geometry of the osteotomy and resultant change in the
      position of the ulnar head did not increase transverse joint reaction forces.
      CLINICAL RELEVANCE: This technique is an alternative to open diaphyseal
      techniques or methods that damage the articular surface of the distal ulna.
      Clinical studies will be necessary to associate the biomechanical correction
      noted in this study with clinical symptom improvement.

PMID- 23978788
TI  - New satiety hormone nesfatin-1 protects gastric mucosa against stress-induced
      injury: mechanistic roles of prostaglandins, nitric oxide, sensory nerves and
      vanilloid receptors.
AB  - Nesfatin-1 belongs to a family of anorexigenic peptides, which are responsible
      for satiety and are identified in the neurons and endocrine cells within the gut.
      These peptides have been implicated in the control of food intake; however, very
      little is known concerning its contribution to gastric secretion and gastric
      mucosal integrity. In this study the effects of nesfatin-1 on gastric secretion
      and gastric lesions induced in rats by 3.5h of water immersion and restraint
      stress (WRS) were determined. Exogenous nesfatin-1 (5-40MUg/kg i.p.)
      significantly decreased gastric acid secretion and attenuated gastric lesions
      induced by WRS, and this was accompanied by a significant rise in plasma
      NUCB2/nefatin-1 levels, the gastric mucosal blood flow (GBF), luminal NO
      concentration, generation of PGE2 in the gastric mucosa, an overexpression of
      mRNA for NUBC2 and cNOS, as well as a suppression of iNOS and proinflammatory
      cytokine IL-1beta and TNF-alpha mRNAs. Nesfatin-1-induced protection was
      attenuated by suppression of COX-1 and COX-2 activity, the inhibition of NOS with
      L-NNA, the deactivation of afferent nerves with neurotoxic doses of capsaicin,
      and the pretreatment with capsazepine to inhibit vanilloid VR1 receptors. This
      study shows for the first time that nesfatin-1 exerts a potent protective action
      in the stomach of rats exposed to WRS and these effects depend upon decrease in
      gastric secretion, hyperemia mediated by COX-PG and NOS-NO systems, the
      activation of vagal and sensory nerves and vanilloid receptors. 

PMID- 23978789
TI  - Antiestrogen-binding site ligands induce autophagy in myeloma cells that proceeds
      through alteration of cholesterol metabolism.
AB  - Multiple myeloma (MM) is a malignancy characterized by the accumulation of clonal
      plasma cells in the bone marrow. Despite extensive efforts to design drugs
      targeting tumoral cells and their microenvironment, MM remains an incurable
      disease for which new therapeutic strategies are needed. We demonstrated here
      that antiestrogens (AEs) belonging to selective estrogen receptor modulators
      family induce a caspase-dependent apoptosis and trigger a protective autophagy.
      Autophagy was recognized by monodansylcadaverin staining, detection of
      autophagosomes by electronic microscopy, and detection of the cleaved form of the
      microtubule-associated protein light chain 3. Moreover, autophagy was inhibited
      by drugs such as bafilomycin A1 and 3-methyladenosine. Autophagy was mediated by
      the binding of AEs to a class of receptors called the antiestrogen binding site
      (AEBS) different from the classical estrogen nuclear receptors. The binding of
      specific ligands to the AEBS was accompanied by alteration of cholesterol
      metabolism and in particular accumulation of sterols: zymostenol or desmosterol
      depending on the ligand. This was due to the inhibition of the cholesterol-5,6
      epoxide hydrolase activity borne by the AEBS. We further showed that the
      phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway mediated
      autophagy signaling. Moreover, AEBS ligands restored sensitivity to dexamethasone
      in resistant MM cells. Since we showed previously that AEs arrest MM tumor growth
      in xenografted mice, we propose that AEBS ligands may have a potent antimyeloma
      activity alone or in combination with drugs used in clinic. 

PMID- 23978790
TI  - Epithelial entry rather than the ensuing systemic immune response determines the
      pathogenicity of two Salmonella enterica serovar Typhimurium strains in a mouse
      model.
AB  - Most studies of Salmonella enterica serovar Typhimurium infection focus only on
      the pathogenicity of one strain. We investigated whether differences in
      pathogenicity of two wild-type S. Typhimurium strains; DT120 and SL1344, were
      related to gut invasion or the resulting immune response. Oral administration of
      a ten-fold lower number of SL1344 (10(6) CFU) as compared to DT120 (10(7) CFU)
      resulted in higher bacterial counts in liver and lymph nodes, and led to massive
      neutrophil infiltration of the spleen, while DT120 administration did not. In
      contrast, administration of the same dose (10(3) CFU) of the two strains
      intravenously resulted in the same levels of bacteria and neutrophils in spleen
      and bone marrow. Oral administration of SL1344 led to an increase in neutrophil
      apoptosis in both spleen and the bone marrow and four out of five mice died
      before Day 8, while in DT120 mice, no increase in neutrophil apoptosis was
      observed and all mice survived until Day 8. This study reveals that two wild-type
      S. Typhimurium strains, despite evoking highly comparable immune responses upon
      intravenous injection, exhibit diverse pathogenicity in mice and thus suggests
      that differences in their invasiveness and survival during gut passage determines
      the success of the ensuing immune response. 

PMID- 23978791
TI  - High mean corpuscular volume is a new indicator of prognosis in acute
      decompensated heart failure.
AB  - BACKGROUND: Accumulating evidence suggests that hematopoiesis, especially
      erythropoiesis, is disturbed in heart failure (HF) for many reasons. Low
      hemoglobin and red blood cell distribution width have emerged as prognostic
      indicators of HF independent of classic predictors. The prognostic implication of
      mean corpuscular volume (MCV) in HF, however, is unknown. In this context, we
      investigated the relationship between MCV and prognosis of acute decompensated HF
      (ADHF). METHODS AND RESULTS: This retrospective cohort study consisted of 458
      consecutive patients with ADHF who had emergency admission to hospital. Patients
      were divided into 2 groups: MCV <=100fl (non-macrocytic group, n=400); and MCV
      >100fl (macrocytic group, n=58). The relationship between MCV and all-cause death
      was tested using Cox proportional hazard models, adjusting for other predictors.
      Mean patient age was 72.4 years and mean MCV was 93.0+/-7.1fl. Hemoglobin was
      significantly lower in the macrocytic group than the non-macrocytic group. During
      the mean follow-up of 20.8 months, a total of 173 deaths (37.9%) occurred. Kaplan
      Meier analysis showed that all-cause death was significantly higher in the
      macrocytic group (log-rank P<0.0001). Cox proportional hazards analysis indicated
      that macrocytosis was an independent predictor of all-cause death (hazard ratio,
      2.288; 95% confidence interval: 1.390-3.643; P=0.0015) after adjustment in the
      multivariate model. CONCLUSIONS: It is proposed for the first time that MCV is an
      independent predictor of all-cause death in patients with ADHF.

PMID- 23978792
TI  - Mn(II) and Cu(II) complexes of a bidentate Schiff's base ligand: spectral,
      thermal, molecular modelling and mycological studies.
AB  - Complexes of manganese(II) and copper(II) of general composition M(L)2X2 have
      been synthesized [L=2-acetyl thiophene thiosemicarbazone and X=Cl(-) and NO3(-)].
      The elemental analysis, molar conductance measurements, magnetic susceptibility
      measurements, mass, IR, UV, NMR and EPR spectral studies of the compounds led to
      the conclusion that the ligand acts as a bidentate manner. The Schiff's base
      ligand forms hexacoordinated complexes having octahedral geometry for Mn(II) and
      tetragonal geometry for Cu(II) complexes. The thermal studies suggested that the
      complexes are more stable as compared to ligand. In molecular modelling the
      geometries of Schiff's base and metal complexes were fully optimized with respect
      to the energy using the 6-31g(d,p) basis set. The mycological studies of the
      compounds were examined against the plant pathogenic fungi i.e. Rhizoctonia
      bataticola, Macrophomina phaseolina, Fusarium odum. 

PMID- 23978793
TI  - An experimental and theoretical study on the novel (Z)-1-((naphthalen-2
      ylamino)methylene)naphthalen-2(1H)-one crystal.
AB  - A novel compound has been synthesized, and its structure has been characterized
      by IR, UV-vis, NMR and X-ray single-crystal determination techniques. The title
      compound crystallizes in the orthorhombic space group P212121 with a=6.2120(4)A,
      b=10.8242(7)A, c=22.3857(15)A and Z=4. The crystal structure has intramolecular N
      H...O hydrogen bond and C-H...Cg interaction. These hydrogen bonds and
      interactions are effective in crystal packing. The optimum molecular geometry,
      conformational analysis, normal mode wavenumbers, infrared and Raman intensities,
      corresponding vibrational assignments, chemical shift assignments, and thermo
      dynamical parameters have been investigated with the help of Density Functional
      Theory (DFT). Detailed vibrational assignments have been made on the basis of
      potential energy distribution (PED). In order to understand the electronic
      transitions of the compound, time dependent DFT (TD-DFT) calculations were
      performed in gas phase. Also, the dipole moment, linear polarizabilities,
      anisotropy and first hyperpolarizabilities values have been computed.

PMID- 23978794
TI  - Tonsillectomy: a simple surgical procedure?

PMID- 23978795
TI  - Hemorrhage after tonsillectomy: does the surgical technique really matter?
AB  - A thorough review of the publications on surgical techniques used for
      tonsillectomy is provided, emphasizing randomized studies and meta-analysis. In
      the assessment of the data it is important to clearly define and categorize the
      types of posttonsillectomy bleeding (PTB), as well as the various factors that
      have been associated with increased PTB. In recent audits of a large number of
      tonsillectomies, the PTB rates seem to concur: 1% early and 2.5% delayed PTB; 10%
      anamnestic, 2% objective, and 2% re-operation PTB. Objective PTB rates beyond 10%
      should require an audit. The bipolar technique seems associated with the least
      early PTB, while the cold technique is associated with the least delayed PTB.
      Because of the lack of large well-conducted randomized trials, it is difficult to
      conclude which technique is the best. With electrocautery techniques, the current
      power should be adjusted to the minimal level providing hemostasis. Surgical
      techniques for tonsillectomy that should probably be abandoned include monopolar
      electrocautery, Coblation, various lasers, and the harmonic scalpel. Vessel
      sealing systems might hold promise and deserve further evaluation. Tonsillotomy
      might be associated with less postoperative pain, but the hemorrhagic advantage
      in randomized studies is not obvious. Tonsil regrowth rates and efficacy to treat
      obstruction need also further evaluation. 

PMID- 23978796
TI  - Comments to ORL 2013;75:123-132 (DOI: 10.1159/000342314).

PMID- 23978797
TI  - Cold versus hot tonsillectomy: state of the art and recommendations.
AB  - An investigation of the risk factors for haemorrhage after tonsillectomy with
      particular reference to the use of bipolar diathermy for tonsillar dissection and
      haemostasis, diathermy power settings and coblation tonsillectomy. The findings
      of the National Prospective Tonsillectomy Audit and subsequent related research
      are summarised and discussed with reference to the issue of use of hot versus
      cold tonsillectomy techniques. Additional unpublished data on coblation
      tonsillectomy is presented. Overall, increased haemorrhage rates were noted for
      diathermy dissection tonsillectomy (adjusted odds ratio 2.47, p < 0.0001) and
      coblation tonsillectomy (adjusted odds ratio 3.07, p < 0.0001) compared to the
      reference category of cold steel tonsillectomy. Use of bipolar diathermy for
      haemostasis only carried an intermediate risk of haemorrhage (adjusted odds ratio
      1.57, p = 0.004). Further investigation of diathermy power settings demonstrated
      a quantitative relationship between increasing power usage and subsequent
      haemorrhage. Use of diathermy for haemostasis at the lowest effective setting may
      carry a comparable risk of haemorrhage to that of cold steel tonsillectomy.
      Recommendations are given on the optimum tonsillectomy technique for both the
      older child or adolescent and the particularly young or low weight child. 

PMID- 23978798
TI  - Comments to ORL 2013;75:136-141 (DOI: 10.1159/000342315).

PMID- 23978799
TI  - How to make tonsillectomy a safer procedure: the anaesthetist's view.
AB  - Anaesthetists use specific drugs peri-operatively to try to decrease the
      incidence and severity of postoperative pain and of postoperative nausea and
      vomiting. These drugs are usually administered pre-operatively with the
      premedication, or intra-operatively when the patient is still anaesthetised. The
      aim of this approach is to prevent the occurrence of intolerable pain or to avoid
      any nausea or vomiting symptoms which may be clearly unpleasant for the patient
      and which interfere with the patient's well-being, recovery and satisfaction.
      However, since most of these drugs are given prophylactically, and since not all
      patients will actually be suffering from intolerable pain or severe nausea and
      vomiting symptoms postoperatively, many patients will receive these drugs
      unnecessarily. Thus, for the individual patient, the risk of suffering from drug
      related adverse reactions without profiting from any benefit may be relevant.
      Perhaps a 'wait-and-see' approach should be considered; especially non-steroidal
      anti-inflammatory drugs or dexamethasone should not be given pre-operatively to
      all patients but should be provided exclusively to those in whom alternative
      analgesics (for instance, paracetamol combined with a weak opioid) or alternative
      anti-emetics (for instance, a setron or droperidol) have failed or are associated
      with unacceptable adverse effects. There is no evidence that prophylactic
      administration of an analgesic or an anti-emetic is more efficacious than the
      therapeutic administration. An interesting alternative to achieve satisfactory
      posttonsillectomy analgesia may be with local anaesthesia swabs that are applied
      onto the wound. 

PMID- 23978800
TI  - Comments to ORL 2013;75:144-151 (DOI: 10.1159/000343706).

PMID- 23978801
TI  - The steroid controversy: where are we?
AB  - Dexamethasone is widely administered to children during elective tonsillectomy to
      reduce the rate of postoperative nausea and vomiting, as well as decrease
      postoperative use of pain medications. Over the past two decades, there has been
      a wealth of literature advocating the practice that has led to endorsement by a
      variety of anesthesia and otolaryngology professional associations. However, the
      publication of a trial that was halted due to a potential dose-dependent
      association between postoperative hemorrhage and dexamethasone raised significant
      scrutiny regarding the practice in 2008. As a result, significant re-evaluation
      of existing data as well as the development and execution of additional trials
      have been pursued in recent years. Ultimately, the body of evidence that
      currently exists appears to support the concept that a single dose of
      perioperative dexamethasone is not associated with undue risk. A decision to
      withdraw dexamethasone from use in pediatric tonsillectomy needs to be weighed
      against the potential of causing increased postoperative nausea, vomiting, pain,
      and resultant hospital readmission. At this point, surgeons and anesthesiologists
      should feel comfortable giving perioperative dexamethasone but must remain
      vigilant for bleeding complications. 

PMID- 23978802
TI  - Comments to ORL 2013;75:155-164 (DOI: 10.1159/000342316).

PMID- 23978803
TI  - Serious complications following tonsillectomy: how frequent are they really?
AB  - INTRODUCTION: Quality assurance in health care involves the evaluation of
      outcomes, cost-benefit ratios, and access to the delivery system. This literature
      review was undertaken to clarify the incidence of serious posttonsillectomy
      complications to better understand the outcome component of quality assurance.
      MATERIAL AND METHODS: A Medline review was undertaken using the key word
      'tonsillectomy' AND each of the following: 'serious', 'complications' and
      'review'; 'meta-analysis', 'Cochrane'; 'life-threatening', 'death' and
      'disability'. RESULTS: 454 articles were identified with the following search
      items in combination with 'tonsillectomy': 'serious' (154), 'complications',
      'review' (24), 'meta-analysis' (38), 'Cochrane' (43), 'life-threatening' (87),
      'death' (91), 'disability' (17). Sixty-seven articles described a complication
      rate and were therefore eligible for review: 22 case reports, 9 case series, 2
      questionnaires and 33 studies with a more or less precise complication rate were
      obtainable. Most articles (n = 30) reported the rate of posttonsillectomy
      hemorrhage with a considerable range. Fifteen articles reported the incidence of
      death, which ranged from 1:7,132 to 1:170,000 and almost always resulted from
      excessive hemorrhage. All other complications were mentioned in case reports.
      CONCLUSION: The most common postoperative complication of tonsillectomy is
      bleeding. However, the incidence varies considerably across studies depending on
      the study design, follow-up and definition of postoperative bleeding. Other
      serious adverse events, such as neurological disabilities, emphysema (with or
      without pneumomediastinum), or vascular problems outside the neck are infrequent.

PMID- 23978804
TI  - Comments to ORL 2013;75:166-173 (DOI: 10.1159/000342317).

PMID- 23978805
TI  - What lessons can be learned from the Austrian events?
AB  - INTRODUCTION: The death of 5 children in Austria below the age of 6 years due to
      posttonsillectomy haemorrhage in 2006 and 2007 led to an intensive discussion on
      the potential life-threatening risks of tonsil surgery. On this occasion, a
      consensus paper with clear recommendations for tonsil surgery was released by the
      Austrian Societies of Otorhinolaryngology, Head and Neck Surgery and Paediatrics
      followed by a nationwide multicentre study. METHODS: All consecutive
      tonsillectomies, tonsillotomies and adenoidectomies performed in public hospitals
      in Austria within 9 months were assessed. Data on all participating patients were
      collected via an online questionnaire requesting patient characteristics, surgery
      details and postoperative haemorrhage. A strict definition for postoperative
      bleeding episodes with 7 severity grades was applied. Every bleeding episode
      after extubation was counted as postoperative bleeding event. RESULTS: The study
      population - all younger than 18 years of age - consisted of 6,765 patients
      (tonsillectomy 2,080, 31%; tonsillotomy 1,292, 19%; adenoidectomy 3,393, 50%).
      Postoperative haemorrhage episodes were reported in 15% after tonsillectomy and
      in 2.3% after tonsillotomy, with the risk increasing parallel to age. Multiple
      bleeding episodes were recorded in one fourth of all tonsillectomy bleedings, but
      were rare after tonsillotomy. Surgical revision under general anaesthesia was
      necessary in 4.2% after tonsillectomy and in 0.9% after tonsillotomy. DISCUSSION:
      As the incidence of tonsillectomy in children younger than 6 years has declined
      following the recommendations of the consensus paper issued in 2007, tonsillotomy
      has become more frequent in this age group. Overnight hospital admission and
      observation is suggested for all patients experiencing postoperative haemorrhage,
      as the occurrence of one minor bleeding doubled the risk of a second severe
      bleeding.

PMID- 23978806
TI  - Comments to ORL 2013;75:175-181 (DOI: 10.1159/000342319).

PMID- 23978807
TI  - Factors influencing the indication for tonsillectomy: a historical overview and
      current concepts.
AB  - Tonsil surgery has been performed for more than 3,000 years. During the 19th
      century when anesthesia became available, techniques were refined and the number
      of procedures performed increased. Repeated throat infections often causing big
      tonsils was the reason why parents asked for the procedure. During the
      preantibiotic era, scarlet fever was feared since potential heart or kidney
      complications were life-threatening. The technique used before 1900 was
      tonsillotomy since neither a fingernail, snare nor the later 'guillotine' were
      used extracapsularly. Bleeding was small and the surgery ambulatory.
      Extracapsular tonsillectomy developed around the turn of the 20th century with
      the purpose of avoiding remnants - the 'focal infection theory' was prevailing.
      The whole tonsil was now extirpated with good visibility of the tonsillar area in
      a deeply anesthetized patient. During the first half of the 20th century, the two
      methods competed, but by 1950, total tonsillectomy had become the only 'correct'
      tonsil surgery. The indication was still recurrent infections. The risk for
      serious bleeding increased; therefore large clinics arose where patients remained
      for at least a week after tonsillectomy. When oral penicillin for children became
      available during the 1960s, the threat of throat infection decreased and the
      number of tonsillectomies declined. The awareness of obstructive problems in
      children rose at the same time when obstructive sleep apnea syndrome became a
      disease for adults (1970s). Tonsillotomy was revived during the 1990s and is
      today used increasingly in many countries. The indication is mainly obstructive
      sleep apnea syndromeor sleep-disordered breathing, especially in small children.
      Total tonsillectomy is still preferred for recurrent infections, which include
      periodic fever/adenitis/pharyngitis/aphthous ulcer syndrome and recurrent
      peritonsillitis. 

PMID- 23978808
TI  - Comments to ORL 2013;75:184-191 (DOI: 10.1159/000342322).

PMID- 23978809
TI  - Indications of pediatric tonsillectomy.
AB  - Possible indications for tonsillectomy include sleep apnea and other obstructive
      sleep-related breathing disorders, recurrent tonsillitis, peritonsillar abscess,
      periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA), and other
      miscellaneous rare conditions. Over the last century indications have changed,
      with a decrease in infectious causes and an increase in sleep apnea disorders.
      Sleep apnea in children is difficult to diagnose short of polysomnography (PSG)
      which is expensive and disturbing, especially in young children. In sleep apnea
      confirmed by PSG, tonsillectomy relieves the trouble in close to 80% of patients.
      What remains unclear is how to diagnose sleep-related breathing disorders without
      PSG and the efficacy of tonsillectomy in this population. Recurrent tonsillitis
      is generally poorly documented and randomized studies assessing the efficacy of
      tonsillectomy are sparse. When frequent infections are present for several years
      (>7 episodes/1 year, >5/2, >3/3) some benefit from tonsillectomy could be found.
      If fewer infectious episodes are present, the benefit of tonsillectomy is low.
      Peritonsillar abscess tends to be treated with quinsy tonsillectomy. Some PFAPA
      and psoriasis children might benefit from tonsillectomy. Tonsillectomy for other
      conditions is not warranted. 

PMID- 23978810
TI  - Comments to ORL 2013;75:193-202 (DOI: 10.1159/000342329).

PMID- 23978812
TI  - Effects of fibrinogen concentrate after shock/resuscitation: a comparison between
      in vivo microvascular clot formation and thromboelastometry*.
AB  - OBJECTIVES: Dilutional coagulopathy after resuscitation with
      crystalloids/colloids clinically often appears as diffuse microvascular bleeding.
      Administration of fibrinogen reduces bleeding and increases maximum clot
      firmness, measured by thromboelastometry. Study objective was to implement a
      model where microvascular bleeding can be directly assessed by visualizing clot
      formation in microvessels, and correlations can be made to thromboelastometry.
      DESIGN: Randomized animal study. SETTING: University research laboratory.
      SUBJECTS: Male Syrian Golden hamsters. INTERVENTIONS: Microvessels of Syrian
      Golden hamsters fitted with a dorsal window chamber were studied using
      videomicroscopy. After 50% hemorrhage followed by 1 hour of hypovolemia
      resuscitation with 35% of blood volume using a high-molecular-weight hydroxyethyl
      starch solution (Hextend, Hospira, MW 670 kD) occurred. Animals were then treated
      with 250 mg/kg fibrinogen IV (Laboratoire francais du Fractionnement et des
      Biotechnologies, Paris, France) or an equal volume of saline before venular
      vessel wall injuries was made by directed laser irradiation, and the ability of
      microthrombus formation was assessed. MEASUREMENTS AND MAIN RESULTS:
      Thromboelastometric measurements of maximum clot firmness were performed at the
      beginning and at the end of the experiment. Resuscitation with hydroxyethyl
      starch and sham treatment significantly decreased FIBTEM maximum clot firmness
      from 32 +/- 9 mm at baseline versus 13 +/- 5 mm after sham treatment (p < 0.001).
      Infusion of fibrinogen concentrate significantly increased maximum clot firmness,
      restoring baseline levels (baseline 32 +/- 9 mm; after fibrinogen administration
      29 +/- 2 mm). In vivo microthrombus formation in laser-injured vessels
      significantly increased in fibrinogen-treated animals compared with sham (77% vs
      18%). CONCLUSIONS: Fibrinogen treatment leads to increased clot firmness in
      dilutional coagulopathy as measured with thromboelastometry. At the microvascular
      level, this increased clot strength corresponds to an increased prevalence of
      thrombus formation in vessels injured by focused laser irradiation.

PMID- 23978813
TI  - Perioperative fluid therapy with tetrastarch and gelatin in cardiac surgery--a
      prospective sequential analysis*.
AB  - OBJECTIVES: To determine clinical outcomes of synthetic colloids, tetrastarch,
      and gelatin, used before and after cardiac surgery. DESIGN: Prospective
      observational cohort study. SETTING: Fifty-bed cardiac ICU. PATIENTS: Six
      thousand four hundred seventy-eight consecutive patients with cardiopulmonary
      bypass surgery. INTERVENTIONS: Fluid therapy in the operating room and on the ICU
      directed at preset hemodynamic goals: 1) hydroxyethyl starch (predominantly 6%
      hydroxyethyl starch 130/0.4) in 2004-2006, n = 2,137; 2) 4% gelatin in 2006-2008,
      n = 2,324; and 3) only crystalloids in 2008-2010, n = 2,017. MEASUREMENTS AND
      MAIN RESULTS: Renal replacement therapy was more common during periods when
      patients received synthetic colloids compared to only crystalloids. Risk of renal
      replacement therapy was greater after hydroxyethyl starch (odds ratio, 2.29; 95%
      CI, 1.47-3.60) and gelatin (odds ratio, 2.75; 95% CI, 1.84-4.16; both p < 0.001)
      compared to crystalloid. Propensity score stratification confirmed greater use of
      renal replacement therapy in the hydroxyethyl starch and gelatin periods compared
      to the crystalloid period (odds ratio, 1.46 [1.08, 1.97]; p = 0.013 and odds
      ratio, 1.72 [1.33, 2.24]; p < 0.001, respectively). Time to vasopressor
      cessation, normalization of serum lactate, and mean arterial pressure did not
      differ among groups. Total fluid requirement was 163 mL/kg in the hydroxyethyl
      starch period, 207 mL/kg in the gelatin period, and 224 mL/kg in the crystalloid
      period. Fluid intake was higher in the crystalloid group only during the first 20
      hours. CONCLUSIONS: In cardiac surgery patients, fluid therapy with perioperative
      administration of synthetic colloids carries a high risk of renal replacement
      therapy and is not more effective than treating with only crystalloids.

PMID- 23978815
TI  - Robust 3D DNA FISH using directly labeled probes.
AB  - 3D DNA FISH has become a major tool for analyzing three-dimensional organization
      of the nucleus, and several variations of the technique have been published. In
      this article we describe a protocol which has been optimized for robustness,
      reproducibility, and ease of use. Brightly fluorescent directly labeled probes
      are generated by nick-translation with amino-allyldUTP followed by chemical
      coupling of the dye. 3D DNA FISH is performed using a freeze-thaw step for cell
      permeabilization and a heating step for simultaneous denaturation of probe and
      nuclear DNA. The protocol is applicable to a range of cell types and a variety of
      probes (BACs, plasmids, fosmids, or Whole Chromosome Paints) and allows for high
      throughput automated imaging. With this method we routinely investigate nuclear
      localization of up to three chromosomal regions.

PMID- 23978814
TI  - Understanding changes in established practice: pulmonary artery catheter use in
      critically ill patients.
AB  - OBJECTIVE: Multiple studies suggest that routine use of pulmonary artery
      catheters is not beneficial in critically ill patients. Little is known about the
      patterns of "uptake" of practice change that involves removal of a device
      previously considered standard of care, rather than adoption of a new technique
      or technology. Our objective was to assess recent pulmonary artery catheter use
      across ICUs and identify factors associated with high use. DESIGN: Cohort study.
      SETTING: U.S. ICUs in Project IMPACT. PATIENTS: Adult ICU admissions from 2001 to
      2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Trends in pulmonary
      artery catheter use from 2001 to 2008 were assessed. For 2006-2008, we compared
      pulmonary artery catheter use across ICUs. We assessed characteristics of ICUs
      and hospitals in the top quartile for in-ICU pulmonary artery catheter placement
      (vs the bottom quartile) using chi-square and t tests and factors associated with
      in-ICU pulmonary artery catheter insertion using multilevel mixed effects
      logistic regression. Total pulmonary artery catheter use decreased from 10.8% of
      patients (2001-2003) to 6.2% (2006-2008; p < 0.001); insertion of pulmonary
      artery catheters in ICU decreased from 4.2% to 2.2% (p < 0.001). In 2006-2008,
      ICUs in the top quartile for in-ICU pulmonary artery catheter insertion (3.4
      25.0% of patients) were more often surgical (54.2% vs 21.7% in the lowest
      quartile, p = 0.070), teaching hospitals (54.2% vs 4.3%, p = 0.001), and had
      surgeon leadership (40.9% vs 13.0%, p = 0.067). After multivariable regression,
      surgical patients (p < 0.001) and all patients in surgical ICUs (p = 0.057) were
      more likely to have pulmonary artery catheters placed in ICU. CONCLUSIONS: Use of
      pulmonary artery catheters in ICU patients has declined but with significant
      variation across units. Removal of this technology has occurred most in
      nonsurgical ICUs and patients.

PMID- 23978816
TI  - Hepatocyte growth factor as a long-term predictor for total and cardiovascular
      mortality in patients on peritoneal dialysis.
AB  - INTRODUCTION:  Hepatocyte growth factor (HGF) is a regenerative protein involved
      in tissue protection and endothelial repair in response to injury. OBJECTIVES: 
      The aim of the study was to assess the effect of increased HGF levels on total
      and cardiovascular (CV) mortality in patients on peritoneal dialysis (PD) during
      6-year follow-up. PATIENTS AND METHODS:  The study included 55 patients (mean
      age, 53 years; median duration of PD, 24 months). The ejection fraction (EF) and
      calcium score (CaSc) were measured. White blood cell (WBC) count and albumin,
      calcium (Ca), phosphorus (Pi), intact parathormone (iPTH), and high-sensitivity C
      reactive protein (hsCRP) levels were measured. Serum levels of HGF, interleukin
      (IL) 6, and IL-18 were determined using enzyme-linked immunosorbent assays.
      RESULTS:  Of all patients, 45% died within 6 years, including 80% from CV
      complications. HGF significantly correlated with the total (hazard ratio [HR],
      1.97; P = 0.03) and CV (HR, 2.04; P = 0.04) mortality in a univariate Cox
      regression model. This was confirmed by a multiple model including age, dialysis
      duration, residual renal function (RRF), albumin, Ca * Pi, EF, and CaSc (HR,
      2.24; P = 0.02 and HR, 2.58; P = 0.02 for total and CV mortality, respectively).
      Factors negatively affecting patients' survival included WBC count, hsCRP, IL-6,
      and CaSc, while higher albumin levels and EF were associated with longer overall
      survival. HGF positively correlated with WBC count (r = 0.30, P = 0.01), hsCRP (r
      = 0.25, P = 0.04), IL-6 (r = 0.46, P = 0.0004), CaSc (r = 0.29, P = 0.03), and
      mean arterial pressure (r = 0.25; P = 0.04) and negatively with RRF (r = -0.31, P
      = 0.02). CONCLUSIONS:  Increased concentrations of proinflammatory cytokines and
      an association between HGF levels and CaSc may indicate higher total and CV
      mortality in patients on PD.

PMID- 23978817
TI  - Evidence for metabolic endotoxemia in obese and diabetic Gambian women.
AB  - OBJECTIVE: Emerging evidence from animal models suggests that translocation of
      bacterial debris across a leaky gut may trigger low-grade inflammation, which in
      turn drives insulin resistance. The current study set out to investigate this
      phenomenon, termed 'metabolic endotoxemia', in Gambian women. METHODS: In a cross
      sectional study, we recruited 93 age-matched middle-aged urban Gambian women into
      three groups: lean (body mass index (BMI): 18.5-22.9 kg m(-2)), obese non
      diabetic (BMI: ?30.0 kg m(-2)) and obese diabetic (BMI: ?30.0 kg m(-2) and
      attending a diabetic clinic). We measured serum bacterial lipopolysaccharide
      (LPS) and endotoxin-core IgM and IgG antibodies (EndoCAb) as measures of
      endotoxin exposure and interleukin-6 (IL-6) as a marker of inflammation. RESULTS:
      Inflammation (IL-6) was independently and positively associated with both obesity
      and diabetes (F=12.7, P<0.001). LPS levels were highest in the obese-diabetic
      group compared with the other two groups (F=4.4, P<0.02). IgM EndoCAb (but not
      total IgM) was highly significantly reduced in the obese (55% of lean value) and
      obese diabetic women (30% of lean; F=21.7, P<0.0001 for trend) compared with lean
      women. CONCLUSION: These data support the hypothesis that gut-derived
      inflammatory products are associated with obesity and diabetes. Confirmation of
      these findings and elucidation of the role of the microbiota, gut damage and the
      pathways for translocation of bacterial debris, could open new avenues for
      prevention and treatment of type 2 diabetes.

PMID- 23978818
TI  - Changes in adipose tissue distribution during pregnancy in overweight and obese
      compared with normal weight women.
AB  - OBJECTIVE: Differences in body fat distribution contribute to the metabolic
      abnormalities associated with overweight and obesity; however, such differences
      have not been adequately explored during pregnancy. Our aim was to compare
      longitudinal trends in maternal abdominal adipose tissue deposition during
      pregnancy in overweight/obese compared with normal weight women. STUDY DESIGN:
      Pregnant women, classified as normal weight (body mass index (BMI) <25 kg m(-2);
      N=61) or overweight/obese (BMI ?25 kg m(-2); N=57), were enrolled in a
      prospective cohort study starting in the first trimester. Maternal subcutaneous
      (smin) and preperitoneal (pmax) fat were measured by ultrasound at five time
      points starting between 6 and 10 weeks gestation. The abdominal fat index (AFI),
      an established marker of visceral adipose tissue, was calculated as the ratio of
      pmax to smin. The trajectories of smin, pmax, cumulative fat index (smin plus
      pmax) and the AFI across pregnancy were analyzed using mixed linear models.
      RESULTS: The rate of maternal weight gain during pregnancy was significantly
      lower for overweight/obese women compared with their non-overweight counterparts
      (P<0.05). Accordingly, the rate of change of pmax and smin differed significantly
      in normal weight compared with overweight/obese women (P=0.0003 and 0.01,
      respectively). The cumulative fat index did not change across gestation in normal
      weight women, whereas it decreased for overweight/obese women (P=0.0005). The log
      AFI increased across pregnancy in both strata, but significantly more rapidly for
      normal weight compared with overweight/obese women (P=0.06). CONCLUSIONS: Adipose
      tissue is preferentially deposited in the more metabolically active visceral
      compartment as pregnancy progresses. However, this process differs in normal
      weight compared with overweight/obese women and may contribute to metabolic
      differences between these groups. Our study is a step toward a more refined
      description of obesity and its consequences during pregnancy.

PMID- 23978819
TI  - Generalization of adiposity genetic loci to US Hispanic women.
AB  - BACKGROUND: Obesity is a public health concern. Yet the identification of
      adiposity-related genetic variants among United States (US) Hispanics, which is
      the largest US minority group, remains largely unknown. OBJECTIVE: To interrogate
      an a priori list of 47 (32 overall body mass and 15 central adiposity) index
      single-nucleotide polymorphisms (SNPs) previously studied in individuals of
      European descent among 3494 US Hispanic women in the Women's Health Initiative
      SNP Health Association Resource (WHI SHARe). DESIGN: Cross-sectional analysis of
      measured body mass index (BMI), waist circumference (WC) and waist-to-hip ratio
      (WHR) were inverse normally transformed after adjusting for age, smoking, center
      and global ancestry. WC and WHR models were also adjusted for BMI. Genotyping was
      performed using the Affymetrix 6.0 array. In the absence of an a priori selected
      SNP, a proxy was selected (r(2)?0.8 in CEU). RESULTS: Six BMI loci (TMEM18,
      NUDT3/HMGA1, FAIM2, FTO, MC4R and KCTD15) and two WC/WHR loci (VEGFA and ITPR2
      SSPN) were nominally significant (P<0.05) at the index or proxy SNP in the
      corresponding BMI and WC/WHR models. To account for distinct linkage
      disequilibrium patterns in Hispanics and further assess generalization of genetic
      effects at each locus, we interrogated the evidence for association at the 47
      surrounding loci within 1 Mb region of the index or proxy SNP. Three additional
      BMI loci (FANCL, TFAP2B and ETV5) and five WC/WHR loci (DNM3-PIGC, GRB14,
      ADAMTS9, LY86 and MSRA) displayed Bonferroni-corrected significant associations
      with BMI and WC/WHR. Conditional analyses of each index SNP (or its proxy) and
      the most significant SNP within the 1 Mb region supported the possible presence
      of index-independent signals at each of these eight loci as well as at KCTD15.
      CONCLUSION: This study provides evidence for the generalization of nine BMI and
      seven central adiposity loci in Hispanic women. This study expands the current
      knowledge of common adiposity-related genetic loci to Hispanic women.

PMID- 23978821
TI  - Colorimetric and fluorometric dual-readout sensor for lysozyme.
AB  - A novel, highly sensitive and selective dual-readout sensor (colorimetric and
      fluorometric) for the detection of lysozyme was proposed. The fluorescence of
      triazolylcoumarin molecules was quenched by Au nanoparticles (AuNPs) initially
      through the fluorescence resonance energy transfer (FRET), after the addition of
      lysozyme, the stronger binding of lysozyme onto the surfaces of AuNPs made
      triazolylcoumarin molecules remove from the AuNPs surface and led to the recovery
      of the fluorescence of triazolylcoumarin molecules, and accompanied by the
      discernable color change of the solution from red to purple. The lowest
      detectable concentration for lysozyme was 50 ng mL(-1) by the naked eye, and the
      limit of detection (LOD) was 23 ng mL(-1) by fluorescence measurements. In
      addition, satisfactory results for lysozyme detection in hen egg white were
      confirmed in the study. Moreover, the presented sensor provides a reliable option
      to determine lysozyme with high sensitivity and selectivity. 

PMID- 23978820
TI  - Role of motor cortex NMDA receptors in learning-dependent synaptic plasticity of
      behaving mice.
AB  - The primary motor cortex has an important role in the precise execution of
      learned motor responses. During motor learning, synaptic efficacy between sensory
      and primary motor cortical neurons is enhanced, possibly involving long-term
      potentiation and N-methyl-D-aspartate (NMDA)-specific glutamate receptor
      function. To investigate whether NMDA receptor in the primary motor cortex can
      act as a coincidence detector for activity-dependent changes in synaptic strength
      and associative learning, here we generate mice with deletion of the Grin1 gene,
      encoding the essential NMDA receptor subunit 1 (GluN1), specifically in the
      primary motor cortex. The loss of NMDA receptor function impairs primary motor
      cortex long-term potentiation in vivo. Importantly, it impairs the synaptic
      efficacy between the primary somatosensory and primary motor cortices and
      significantly reduces classically conditioned eyeblink responses. Furthermore,
      compared with wild-type littermates, mice lacking NMDA receptors in the
      [corrected] primary motor cortex show slower learning in Skinner-box tasks. Thus,
      primary motor cortex NMDA receptors are necessary for activity-dependent synaptic
      strengthening and associative learning.

PMID- 23978837
TI  - Influence of layer thickness and composition of cross-linked multilayered oil-in
      water emulsions on the release behavior of lutein.
AB  - Multilayering and enzymatic cross-linking of emulsions may cause alterations in
      the release behavior of encapsulated core material due to changes in thickness,
      porosity and permeability of the membrane. An interfacial engineering technology
      based on the layer-by-layer electrostatic deposition of oppositively charged
      biopolymers onto the surfaces of emulsion droplets in combination with an
      enzymatic treatment was used to generate emulsions with different droplet
      interfaces to test this hypothesis. Release behavior of primary, secondary
      (coated) and laccase-treated secondary emulsions carrying lutein, an oxygenated
      carotenoid, was characterized and studied. Fish gelatin (FG), whey protein
      isolate (WPI) and dodecyltrimethylammonium bromide (DTAB) were used as primary
      emulsifiers under acidic conditions (pH 3.5) to facilitate the adsorption of a
      negatively charged biopolymer (sugar beet pectin). Laccase was added to promote
      cross-linking of adsorbed beet pectin. The release of lutein-loaded emulsions was
      investigated and quantified by UV-Vis spectrophotometry. Primary WPI-stabilized
      emulsions showed a five times higher release of lutein after 48 h than secondary
      emulsions (pH 3.5). Primary DTAB-stabilized emulsions released 7.2% of
      encapsulated lutein within the observation period, whereas beet pectin-DTAB
      coated emulsions released only 0.13% of lutein. Cross-linking of adsorbed pectin
      did not significantly decrease release of lutein in comparison to non-cross
      linked secondary emulsions. Additionally, release of lutein was also affected by
      changes in the pH of the surrounding medium. Results suggest that modulating the
      interfacial properties of oil-in-water emulsion by biopolymer deposition and/or
      cross-linking may be a useful approach to generate food-grade delivery systems
      that have specific release-over-time profiles of incorporated active ingredients.

PMID- 23978838
TI  - Imaging techniques in electrophysiology and implantable device procedures:
      results of the European Heart Rhythm Association survey.
AB  - The purpose of this European Heart Rhythm Association (EHRA) survey is to assess
      the implementation and use of imaging techniques in cardiac electrophysiology
      (EP) and device procedures across European cardiovascular centres. Forty European
      centres, all members of the EHRA EP research network, responded to this survey.
      Thirty-one centres (88%) use transthoracic echocardiography (TTE) to evaluate
      left atrial size and/or volume before atrial fibrillation (AF) ablation. Sixteen
      centres (46%) perform delayed-enhancement cardiac magnetic resonance imaging
      (MRI) to guide ventricular tachycardia ablation. Electroanatomical mapping (EAM)
      systems are available in >65% of responding centres and the use of robotic
      catheter and remote magnetic navigation systems is limited to <10%. Fusion of EAM
      data with cardiac computed tomography (CT) and/or MRI is performed in up to 43%
      of AF ablation procedures. Seventeen out of 35 (49%) responding centres also
      perform TTE to predict a favourable response to cardiac resynchronization therapy
      (CRT). Imaging of the cardiac venous system with CT and identification of
      myocardial scar using CT or MRI, is not routinely performed in the majority of
      centres [32 (91%) and 26 (75%) centres, respectively) prior to CRT. This EHRA
      survey shows that several imaging techniques are used to guide catheter ablation
      and CRT procedures in European centres. Echocardiographic imaging, EAM
      techniques, and cardiac CT/MRI are commonly used. 

PMID- 23978839
TI  - Epithelial urinary bladder tumors from cows with enzootic hematuria: structural
      and cell cycle-related protein expression.
AB  - Thirty-nine epithelial bladder tumor samples from 37 animals affected with bovine
      enzootic hematuria (BEH) were selected for immunohistochemical studies. The
      expression of structural proteins such as uroplakin III (UPIII) and cytokeratin 7
      (CK7) and the cell cycle-related proteins cyclin D1 and p53 were evaluated in
      urothelial papillomas and carcinomas. Loss of UPIII and CK7 expression was seen
      in both high-grade and high-stage urothelial carcinomas (P < .001 and P < .02).
      Cyclin D1 expression showed no statistically significant association with grade
      or stage. In contrast, p53 immunoreactivity was positive in high-grade and high
      stage carcinomas (P < .05 and P < .01), confirming its association with the
      highest malignant behavior of the bladder tumors in BEH. 

PMID- 23978840
TI  - Diagnostic exercise: hemolysis and sudden death in lambs.
AB  - Within a 24-hour period, 7 out of 200 three- to four-week-old pastured Katahdin
      lambs died after showing clinical signs of hemoglobinuria, red-tinged feces,
      weakness, and recumbency. One of the lambs that was examined clinically before
      natural death also had abdominal pain, trembling, tachycardia, and severe anemia
      with a packed cell volume of 4%. Pathologic findings included icterus,
      hemoglobinuric nephrosis, dark red urine, pulmonary edema, hydrothorax,
      splenomegaly, and acute centrilobular to midzonal hepatocellular degeneration and
      necrosis with cholestasis. The differential diagnoses and diagnostic workup to
      achieve the diagnosis are briefly discussed.

PMID- 23978842
TI  - [Contribution of volume ultrasound in the evaluation and prenatal care of fetal
      cardiovascular anomalies].
AB  - OBJECTIVES: To highlight the value of 3D ultrasound in the prenatal assessment of
      fetal cardiovascular abnormalities. PATIENTS AND METHODS: A retrospective offline
      analysis of volume datasets of fetuses diagnosed with cardiovascular anomalies by
      2D ultrasound was performed. RESULTS: Thirty-four fetuses with 38 cardiac
      malformations were evaluated. Mean gestational age at diagnosis was 26 weeks.
      Isolated cardiovascular malformations were detected in 23 fetuses. Extracardiac
      abnormalities were identified in eight fetuses. Ten terminations of pregnancy
      were performed. CONCLUSION: Offline analysis of cardiovascular anomalies
      conferred significant diagnostic advantages over 2D ultrasound. 3D ultrasound is
      a valuable tool for the prenatal diagnosis and the management of congenital heart
      diseases.

PMID- 23978843
TI  - Impact of ductal carcinoma in situ terminology on patient treatment preferences.

PMID- 23978844
TI  - How far up the ladder should we go?

PMID- 23978845
TI  - NICE public health guidance update.

PMID- 23978846
TI  - Cochrane update: identifying health-related research resources relevant to low-
      and middle-income countries.

PMID- 23978847
TI  - Isolation and genome-wide expression and methylation characterization of CD31+
      cells from normal and malignant human prostate tissue.
AB  - Endothelial cells (ECs) are an important component involved in the angiogenesis.
      Little is known about the global gene expression and epigenetic regulation in
      tumor endothelial cells. The identification of gene expression and epigenetic
      difference between human prostate tumor-derived endothelial cells (TdECs) and
      those in normal tissues may uncover unique biological features of TdEC and
      facilitate the discovery of new anti-angiogenic targets. We established a method
      for isolation of CD31+ endothelial cells from malignant and normal prostate
      tissue obtained at prostatectomy. TdECs and normal-derived ECs (NdECs) showed
      >90% enrichment in primary culture and demonstrated microvascular endothelial
      cell characteristics such as cobblestone morphology in monolayer culture, diI
      acetyl-LDL uptake and capillary-tube like formation in Matrigel(r). In vitro
      primary cultures of ECs maintained expression of endothelial markers such as
      CD31, von Willebrand factor, intercellular adhesion molecule, vascular
      endothelial growth factor receptor 1, and vascular endothelial growth factor
      receptor 2. We then conducted a pilot study of transcriptome and methylome
      analysis of TdECs and matched NdECs from patients with prostate cancer. We
      observed a wide spectrum of differences in gene expression and methylation
      patterns in endothelial cells, between malignant and normal prostate tissues.
      Array-based expression and methylation data were validated by qRT-PCR and
      bisulfite DNA pyrosequencing. Further analysis of transcriptome and methylome
      data revealed a number of differentially expressed genes with loci whose
      methylation change is accompanied by an inverse change in gene expression. Our
      study demonstrates the feasibility of isolation of ECs from histologically normal
      prostate and prostate cancer via CD31+ selection. The data, although preliminary,
      indicates that there exist widespread differences in methylation and
      transcription between TdECs and NdECs. Interestingly, only a small proportion of
      perturbed gene was overlapped between American (AA) and Caucasian American (CA)
      patients with prostate cancer. Our study indicates that identifying gene
      expression and/or epigenetic differences between TdECs and NdECs may provide us
      with new anti-angiogenic targets. Future studies will be required to further
      characterize the isolated ECs and determine the biological features that can be
      exploited in the prognosis and therapy of prostate cancer. 

PMID- 23978848
TI  - [SETSUYAKU-BAG Campaign--investigation of outpatient's leftover drugs and
      promotion of proper reuse of leftover drugs to reduce medical expenses].
AB  - Pharmacists, being compensated through the new dispensing fee, are required to
      educate patients on their adhesion to the use of prescribed drugs, and to
      inventory the levels of leftover drugs in outpatients. Recently, Fukuoka City
      Pharmaceutical Association started a campaign for regulating leftover drugs
      (Setsuyaku Bag Campaign). Thirty-one pharmacies joined the campaign. Pharmacists
      distributed convenience bags, called 'SETSUYAKU-BAG.' The patients put their
      leftover drugs in the bags and brought them to community pharmacies. The
      pharmacists inventoried the returned drugs and reported their results to the
      doctors. The doctors adjusted the prescriptions accordingly. We counted and
      analyzed old and new inventories. The number of leftover drugs was 252, for a
      total value was Y839655. Cost of leftover drug prescriptions could be reduced by
      Y702695, and the value of drugs thrown away was Y94801. In total, we could reduce
      the amount of leftover drugs by 83.7%. The cost of leftover drug for one dose
      package (ODP) is higher than that for non-ODP. However, there were no significant
      differences in results per age, sex, number and kinds of drugs, prescription days
      and premium contribution rate. These results suggest that prescription regulation
      by inventory of leftover drugs in community pharmacies could significantly reduce
      overall medical expenses. Further studies are necessary in order to account for
      patients' health, and to establish more efficient patient education to raise
      outpatients' adherence to the new programs.

PMID- 23978849
TI  - The effect of photosynthesis time scales on microalgae productivity.
AB  - Microalgae are often seen as a potential biofuel producer. In order to predict
      achievable productivities in the so called raceway culturing system, the dynamics
      of photosynthesis has to be taken into account. In particular, the dynamical
      effect of inhibition by an excess of light (photoinhibition) must be represented.
      We propose a model considering both photosynthesis and growth dynamics. This
      model involves three different time scales. We study the response of this model
      to fluctuating light with different frequencies by slow/fast approximations.
      Therefore, we identify three different regimes for which a simplified expression
      for the model can be derived. These expressions give a hint on productivity
      improvement which can be expected by stimulating photosynthesis with a faster
      hydrodynamics. 

PMID- 23978850
TI  - Pentynyl dextran as a support matrix for immobilization of serine protease
      subtilisin Carlsberg and its use for transesterification of N-acetyl-L
      phenylalanine ethyl ester in organic media.
AB  - In this study, serine protease (subtilisin Carlsberg) was immobilized on pentynyl
      dextran (PyD, O-alkynyl ether of dextran, 1) and used for the transesterification
      of N-acetyl-L-phenylalanine ethyl ester (2) with different aliphatic (1-propanol,
      1-butanol, 1-pentanol, 1-hexanol) and aromatic (benzyl alcohol, 2-phenyl ethanol,
      4-phenyl-1-butanol) alcohols in tetrahydrofuran (THF). The effect of carbon chain
      length in aliphatic and aromatic alcohols on initial and average
      transesterification rate, transesterification activity of immobilized enzyme and
      yield of the reaction under selected reaction conditions was investigated. The
      transesterification reactivity of the enzyme and yield of the reaction increased
      as the chain length of the alcohols decreased. Furthermore, almost no change in
      yield was observed when the immobilized enzyme was repeatedly used for selected
      alcohols over six cycles. Intrinsic fluorescence analysis showed that the
      catalytic activity of the immobilized enzyme in THF was maintained due to
      retention of the tertiary structure of the enzyme after immobilization on PyD
      (1). 

PMID- 23978852
TI  - Sternalis. An anatomic variant of chest wall musculature.
AB  - OBJECTIVE: To study the prevalence of sternalis muscle in the Kingdom of Saudi
      Arabia (KSA) and resolve the question of its genesis by studying the innervation
      of this uncommon variant of anterior chest wall musculature. METHODS: A
      morphological study of 75 adult cadavers of both sexes was carried out over a 5
      year period by macroscopic dissection. We also retrospectively studied the
      medical records of 1580 adult females who had undergone screening and diagnostic
      mammographic imaging at King Khalid University Hospital, Riyadh, KSA, from 1997
      to 2001. RESULTS: Out of 75 cadavers studied, 3 cases of sternalis muscle were
      observed. Two adult male cadavers had well developed bilateral sternalis muscles
      whereas one female cadaver exhibited right sided unilateral sternalis. All 5
      sternalis muscles were positioned vertically, in a parasternal position
      superficial to the medial part of pectoralis major and innervated by branches of
      intercostal nerves. None of the 1580 women, however, who had undergone
      mammographic imaging were found to be sternalis positive. CONCLUSION: Consistent
      with other geographic populations of the world, the frequency of sternalis in KSA
      is approximately 4%; however, its innervation by the intercostal nerves, as
      observed in our study is not common. This study highlights the need for
      familiarity with sternalis, which may mimic a focal density in medial breast
      craniocaudal mammograms and may be encountered during reconstructive surgery of
      breast and chest wall.

PMID- 23978851
TI  - In vivo imaging method to distinguish acute and chronic inflammation.
AB  - Inflammation is a fundamental aspect of many human diseases. In this video
      report, we demonstrate non-invasive bioluminescence imaging techniques that
      distinguish acute and chronic inflammation in mouse models. With tissue damage or
      pathogen invasion, neutrophils are the first line of defense, playing a major
      role in mediating the acute inflammatory response. As the inflammatory reaction
      progresses, circulating monocytes gradually migrate into the site of injury and
      differentiate into mature macrophages, which mediate chronic inflammation and
      promote tissue repair by removing tissue debris and producing anti-inflammatory
      cytokines. Intraperitoneal injection of luminol (5-amino-2,3-dihydro-1,4
      phthalazinedione, sodium salt) enables detection of acute inflammation largely
      mediated by tissue-infiltrating neutrophils. Luminol specifically reacts with the
      superoxide generated within the phagosomes of neutrophils since bioluminescence
      results from a myeloperoxidase (MPO) mediated reaction. Lucigenin (bis-N
      methylacridinium nitrate) also reacts with superoxide in order to generate
      bioluminescence. However, lucigenin bioluminescence is independent of MPO and it
      solely relies on phagocyte NADPH oxidase (Phox) in macrophages during chronic
      inflammation. Together, luminol and lucigenin allow non-invasive visualization
      and longitudinal assessment of different phagocyte populations across both acute
      and chronic inflammatory phases. Given the important role of inflammation in a
      variety of human diseases, we believe this non-invasive imaging method can help
      investigate the differential roles of neutrophils and macrophages in a variety of
      pathological conditions.

PMID- 23978853
TI  - An evidence-based review of Dopamine receptor agonists in the treatment of
      Parkinson's disease.
AB  - Apomorphine and certain ergot alkaloids (bromocriptine, lisuride and pergolide)
      have been available for several decades; for the last few years, they were joined
      by newer dopamine agonists (cabergoline, pramipexole and ropinirole) most of them
      are non-ergolines. Each of these dopamine agonists has its own pharmacological
      characteristics and occupies a place in the pharmacotherapy of Parkinsons
      disease. In this evidence-based review, emphasis is put on the clinical efficacy
      of dopamine agonists in early and advanced Parkinsons disease, and where possible
      comparative evidence regarding their efficacy and safety is provided. In
      addition, their clinical pharmacokinetics, adverse effect profiles and most
      relevant interactions will be summarized. 

PMID- 23978854
TI  - Treatment of status epilepticus in children.
AB  - Status epilepticus is a medical emergency that requires prompt recognition and
      urgent treatment. Successful management of status epilepticus in children depends
      upon implementation of a treatment protocol modified according to current
      practices as well as availability of antiepileptic medications, out of hospital
      emergency services and intensive-care facilities. We propose a treatment protocol
      for status epilepticus in children in the Kingdom of Saudi Arabia. 

PMID- 23978855
TI  - Status epilepticus. Can the incidence be reduced?
AB  - OBJECTIVE: To identify high risk groups for the development of convulsive status
      epilepticus (CSE) in an attempt to decrease the incidence and to determine both
      the time to access to medical care and the use of prehospital treatment in an
      attempt to reduce the duration of seizing. METHODS: Retrospective study record
      analysis of all cases of CSE in children, at the King Abdul-Aziz University
      Hospital, Jeddah, Kingdom of Saudi Arabia from June 1997 to June 2000. RESULTS:
      During the study period there were 24 cases of CSE. The major etiologic factors
      were chronic neurological disorders, idiopathic epilepsy, and acute cerebral
      insults. All but one of the chronic epileptics in the study group had at least
      one identifiable risk factor for the evolution of breakthrough seizures into
      status epilepticus (SE). Mortality was 12.5% and chronic neuro-behavioral
      morbidity in previously normal children was 17%. The average total duration of
      seizing was 2.3 hours, with an average of 52 minutes prior to arrival in the
      hospital. Prehospital rectal diazepam was administered by the family in only 2
      instances, and in both cases the patients were overdosed. CONCLUSION: The
      identification of risk factors for CSE can serve 2 purposes: Focus targeted
      patient and family education, and a checklist for emergency room personnel to
      recognize those presenting with breakthrough seizures who are susceptible to SE,
      aiding in management decision making. The incidence of SE can be reduced by
      abbreviating the duration of breakthrough seizures. This can be achieved both by
      more widespread yet proper use of rectal diazepam at home, and by auditing the
      process of patient or family education.

PMID- 23978856
TI  - Impact of early surgical correction of curves in paralytic scoliosis.
AB  - OBJECTIVE: The purpose of this investigation was to investigate the advantages of
      early surgery in patients suffering from neuromuscular scoliosis. METHODS:
      Between January 1992 and January 1998, 20 patients with paralytic scoliosis, with
      an average age of 15 years, were treated surgically in the Department of
      Orthopedic Surgery, University Hospital, Feiburg, Germany. The parameter
      investigations included correction of the scoliosis independent of preoperative
      curves, operation time independent of Cobb angles, complications and blood loss.
      Surgery included a dorsal semi rigid instrumentation with pedicle screws in the
      lumbo-sacral region and sublaminar wiring in the thoracic area. RESULTS: The
      preoperative scoliotic curve measured 73.1 degrees, the postoperative curve 24.5
      degrees, the mean correction was 66.4%. The thoracic kyphosis could be corrected
      from 13.9-25.7 degrees. The operation time was longer and the correction was less
      if high Cobb angles were found preoperatively. Two wound infections were
      observed. Rod breakage following a pseudarthrosis occurred in one patient, a
      refusion was necessary. CONCLUSION: Cobb angles alone should not be the standard
      to indicate surgery in neuromuscular scoliosis. If a decreased functional
      ability, pelvic obliquity or trunk decompensation with reduced vital capacity are
      found, surgery is more dangerous while the obtained correction is less.
      Therefore, we recommend early surgery.

PMID- 23978857
TI  - Intraoperative monitoring of the facial nerve.
AB  - OBJECTIVE: Intraoperative facial nerve monitoring (FNM) was used to assess the
      anatomical and physiological integrity of the facial nerve during neurotological,
      otological, and parotid surgeries. Why monitor the facial nerve? There are
      several reasons to perform FNM. First of all, it alerts the surgeon when
      something potentially harmful was carried out to the nerve. When the regional
      anatomy is confusing, it allows positive identification of the nerve. Finally,
      the integrity of the facial nerve is assessed at the end of the procedure.
      METHODS: Eighty seven patients who underwent intraoperative monitoring of facial
      nerve between 1991 and 1996 at the King Fahad National Guard Hospital, Riyadh,
      Kingdom of Saudi Arabia were studied. The device used was the nerve integrity
      monitor manufactured by Xomed. The device works when a physiologically intact
      facial nerve is stimulated, the muscles that are innervated by this nerve will
      contract. RESULTS: In otologic surgery, FNM signals the unintentional mechanical
      stimulation of the facial nerve during surgery, it predicts the dehiscence in the
      bony covering of the nerve and it allows mapping the nerve through soft tissue
      and bone. Facial nerve injury is the most devastating complication of otologic
      surgery particularly when anatomy is distorted by previous surgery, granulation
      tissue or cholesteatoma distorts anatomy, and in rare instances by an anolomous
      course. However, it is unlikely to be injured when it has been identified. The
      surgical treatment of recurrent parotid tumor can be challenging. The main aim of
      surgery is complete removal of tumor and preservation of facial nerve.
      CONCLUSION: Facial nerve monitoring assists early nerve identification and
      decreases the nerve trauma. However, as an adjunct, it has proved extremely
      beneficial. In this paper, the facial nerve was monitored intraoperatively in 87
      cases with different pathologies. It is certainly helpful in revision mastoid
      surgery and in removal of recurrent parotid tumor. Intraoperative monitoring of
      the facial nerve plays an important role in identification and preservation of
      the facial nerve during otological and parotid surgeries.

PMID- 23978858
TI  - Clinical evaluation of optic atrophy in patients with neurological disorders.
AB  - OBJECTIVE: Optic atrophy is a pathological term applied to optic nerve shrinkage
      from any process that produces degeneration of axons in the anterior visual
      system (the retino-geniculate pathway). The pathologist can make the diagnosis of
      optic atrophy by direct observation of the histopathological changes in the optic
      nerve. The clinician is restricted to indirect evidence by observing the optic
      nerve as it enters the eye and through testing its function. METHODS: Fifty
      patients with bilateral or unilateral optic atrophy, were collected randomly from
      several teaching hospitals in Baghdad, Iraq, between August 1998 and June 1999.
      Those patients included in this study had ophthalmoscopic abnormalities of the
      optic disc in addition to defective visual function that could be localized to
      the optic nerve. RESULTS: The defects in visual function varied between patients
      according to the disease process and duration of illness. Eight-seven percent of
      patients had visual acuity impairment, 74.4% had visual field defect, 58.5% had
      impairment in color perception, 64% had defective pupillary response to light and
      88.4% had prolonged visual evoked potential (VEP) responses. CONCLUSION: Patients
      who met the criteria for optic atrophy have different and unequal changes in
      optic nerve functions, ranging from 58.5% for color saturation test to 88.4% for
      VEP. Forty percent of patients with optic atrophy were discovered accidentally.

PMID- 23978859
TI  - Clinical presentation of acute bacterial meningitis in Qatar.
AB  - OBJECTIVE: To study the changes in the epidemiology of bacterial meningitis in
      the era of the Hemophilus influenzae (H. influenzae) type b vaccine and
      pneumoccous resistance. METHODS: Retrospective study which included patients
      admitted to Hamad Medical Corporation, Doha, Qatar between January 1998 through
      to December 2000 with positive cerebrospinal fluid culture. RESULTS: Thirty-seven
      patients with culture proven bacterial meningitis were described. Streptococcus
      pneumoniae (S. pneumoniae) and H. influenzae were the most common organisms,
      accounting for 30% and 24% of cases. Fever, neck stiffness, vomiting, and bulging
      fontanel were the most frequent presenting features. Fifty four percent of S.
      pneumoniae isolates were resistant to penicillin, and 22% of H. influenzae were
      resistant to ampicillin, but both were sensitive to ceftriaxone. No cases of
      Listeria monocytogenes meningitis were diagnosed. Morbidity was 32%, and
      mortality 5%. Poor outcome was associated with altered mental status on
      admission. CONCLUSION: Bacterial meningitis is a serious illness in our community
      with significant morbidity and mortality. Streptococcus pneumoniae and H.
      influenzae are the most frequent pathogens causing meningitis in our community.
      As there is no bacterial resistance (S. pneumoniae and H. influenzae) reported
      against ceftrixone, we recommend ceftriaxone alone as empiric therapy for
      patients with no comorbid conditions presenting with community acquired bacterial
      meningitis. A continuous surveillance for changes in the microbiology of
      organisms causing bacterial meningitis or their sensitivity in our community is
      essential to update these recommendations.

PMID- 23978860
TI  - Clinical evaluation of disabled children in Al-Qassim region, Saudi Arabia.
AB  - OBJECTIVE: The study was conducted as part of an overall evaluation for an
      outreach program to evaluate the clinical status of all the participating
      children, identify management problems, if any, and offer relevant
      recommendations. METHODS: All the participating children were subjected to a
      detailed clinical evaluation using a structured questionnaire developed for the
      purpose. The subjects of this study were registered in the Center for Disabled
      Children in Buraidah and Unaizah, Al-Qassim region, Kingdom of Saudi Arabia. This
      study was conducted in 1998 to include all registered children in the centers,
      which were established in 1994. RESULTS: One hundred and eleven children were
      evaluated, 51.8% were males. Average age was 72.31 months (standard deviation
      32.99). The children fell into 3 diagnostic groups: Cerebral palsy (CP) group
      (n=41), chromosomal abnormalities group (n=36) and miscellaneous group (n=34).
      Mothers were the direct care-givers in 98.1% of cases. The sample as a whole
      suffered from a number of disabilities, the most common of which was severe
      speech difficulty (88.3%). Fifty seven percent of the children were severely
      malnourished. The CP group suffered most, as they were significantly fewer
      mobiles and more dependants on the care-giver. History of neonatal asphyxia and
      severe malnutrition at the time of examination were also significantly more
      common in this group. CONCLUSION: This group of disabled children is enjoying a
      comprehensive rehabilitation service delivered through an efficient outreach
      program. It was observed that the families need extra support to improve
      mobility, nutrition and communication abilities of the participating children.

PMID- 23978861
TI  - Does ascorbic acid protect against vanadium neurotoxicity in different regions of
      rat brain?
AB  - OBJECTIVE: Ascorbic acid is a powerful antioxidant and protects against lipid
      peroxidation in cerebral membrane. The objective of the study was to investigate
      protective effects of ascorbic acid on lipid peroxidative damage and perturbation
      of enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and acetylcholinesterase
      (AChE) in discrete regions of rat brain after vanadium exposure. METHODS: This
      study was carried out at Al-Arab Medical University, Benghazi, Libya, from 1995
      to 1996. To investigate the effect of this vitamin on vanadium neurotoxicity in
      brain, adult rats were injected with L-ascorbic acid (1.0 g/kg body weight) and
      elemental vanadium (2.5 mg/kg body weight) alone or concomitantly for 8
      consecutive days by the intraperitoneal route. RESULTS: Vanadium intoxication
      significantly enhanced the occurrence of lipid peroxidation in discrete regions
      of rat brain. The increase in lipid peroxidation was inhibited by ascorbic acid
      treatment. On the other hand, ascorbic acid content was higher, but the activity
      of G6PDH and AChE was significantly inhibited in discrete regions of rat brain
      after vanadium neurotoxicity. Interestingly, however, co-administration (L
      ascorbic acid + vanadium) reversed the levels of ascorbic acid together with the
      activity of G6PDH and AChE towards normal values. The neurohistopathology showed
      that vanadium is involved in an interaction with myelin and deleterious effect of
      metal resulted in edema and marked vacuolation of white matter or segmental de
      myelinantion in the hypothalamus region of rat brain. Ascorbic treatment,
      however, did not show any effect on histopathological changes. CONCLUSION: These
      results suggested that vanadium neurotoxicity initiated lipid peroxidative damage
      and interferes with enzymes, G6PDH and AChE, in rat brain. These events may lead
      to sensorimotor dysfunctions and axonal degeneration. On the other hand, ascorbic
      acid therein reduced the toxicity of vanadium.

PMID- 23978862
TI  - Compliance with appointment and medications in a pediatric neurology clinic at a
      University Hospital in Riyadh, Saudi Arabia.
AB  - OBJECTIVE: The objectives of the study are to estimate the rate of epileptic
      patients' compliance with appointments and medications in a pediatric neurology
      clinic. Also to study the factors associated with non-compliance and to determine
      the parents' perceived reasons for non-compliance with appointments. METHODS: It
      is a prospective study in which 147 epileptic children who attended the neurology
      clinic during the first 12-months of the study period were included. Patients
      were recruited into the study after their parents were interviewed using a
      detailed questionnaire; their compliance with appointments was monitored
      prospectively over at least a one year from their recruitment into the study. The
      parents of the other 70 patients who did not attend the clinic were telephoned.
      Only 32 replied and were asked about the reasons for non-attendance to the
      clinic. RESULTS: Eighty-six percent of the patients' parents stated that they
      were complying with the medications while only 53% of them did not miss any
      appointment to the clinic during the study period. Compliers with appointments
      were more likely to comply with their medications too. Children with grand-mal
      epilepsy and absence seizures were found to be more likely to comply with taking
      medications than patients with febrile, rolandic and myoclonic seizures (P=0.01).
      Health belief model factors associated with non-compliance were 1. Children
      encountering side effects from their medications 2. Parents who were not
      satisfied with the provided services 3. Parents who thought that alternative
      medicine is more effective than traditional medicine 4. Parents who think that
      their children are not susceptible. Patients' perceived main reasons for non
      compliance were wrongly registered appointments (27.5%), forgetfulness (22.5%)
      and busy parents. CONCLUSION: Failure to keep the clinic appointment is an
      indicator of poor compliance with medications. A telephone call is recommended to
      reduce the role of clinic non-compliance. Developing a questionnaire form to
      investigate parents health belief model could be used routinely by social workers
      and then health education could be tailored for each patient and parent.

PMID- 23978863
TI  - D-Penicillamine induced myasthenia gravis.
AB  - Myasthenia gravis is a disorder of impaired neuromuscular transmission resulting
      in weakness and abnormal fatigability on exertion, improved by anti-acetyl
      cholinesterase drugs. A number of drugs are known to exacerbate myasthenia gravis
      or interfere with neuromuscular transmission. We report a case of D-penicillamine
      induced myasthenia gravis who developed ptosis, diplopia and easy fatigability, 4
      years after initiation of the drug for Wilson's disease. On stopping the drug,
      within 3 months all her symptoms disappeared without any anti-acetyl
      cholinesterase drugs. Thus, the onset of drug induced myasthenia gravis could be
      insidious but the withdrawal of the drug leads to rapid recovery. 

PMID- 23978864
TI  - Acute sporadic brachial plexus neuropathy.
AB  - A 43-year-old patient presented with acute sporadic brachial plexus. Diagnosis
      was based on clinical and neurophysiological findings. This case highlights that
      early diagnosis of this clinical disorder can prevent unnecessary
      neuroradiological or neurosurgical interventions. 

PMID- 23978865
TI  - Post-varicella Guillain Barre syndrome.
AB  - Varicella-zoster virus (VZV) infection has not often been related to the
      development of Guillain Barre Syndrome (GBS). However, the close temporal
      relationship noted between varicella infection and the onset of GBS suggests the
      participation of VZV in the etiopathogenesis of GBS. Very few cases have been
      reported showing this relationship. This report describes 2 cases highly
      suggestive of this association. 

PMID- 23978867
TI  - Shared psychotic disorder.
AB  - We describe a rare case of psychotic disorder, with unique family dynamics and
      management difficulties. 

PMID- 23978866
TI  - Central fever due to hypothalamic lesion in a patient with tuberculous
      meningitis.
AB  - Abnormalities of body temperature are perhaps the most common features in many
      systemic pathologic processes. Such pathologic alterations are nearly always the
      result of extrinsic factors (for example, systemic pyrogens) which affect the
      hypothalamic thermoregulatory center by way of circulatory system. Much less
      common is alterations in temperature regulation resulting from intrinsic lesions
      of the thermoregulatory center in the hypothalamus. We report a patient with
      tuberculous meningitis who continued to have persistent fever despite the
      satisfactory treatment of her tuberculosis. A central thermoregulatory defect was
      documented and was attributed to a small structural lesion in the anterior
      hypothalamus. 

PMID- 23978868
TI  - Peripheral edema with Valproate therapy.

PMID- 23978869
TI  - Retrospective review of image quality of CT in polytrauma patients: comparison of
      patients scanned using a scoop stretcher and without a scoop stretcher.
AB  - Increasingly pre-hospital trauma management involves transfer of patients using a
      scoop stretcher; a number of computed tomography (CT) compatible scoops have
      recently appeared on the market. We sought to evaluate any differences in image
      quality in polytrauma patients scanned in a scoop stretcher. CT studies of 234
      consecutive patients presenting between December 2011 and August 2012 at our
      regional level 1 tertiary trauma centre were retrospectively reviewed. Patients
      were allocated into two groups: those scanned with a scoop stretcher and without.
      CTs were reviewed by a consultant radiologist and two senior radiology trainees
      and graded separately for quality/artefact. A scale of 1-5 was employed: 1
      uninterpretable, 2-borderline image quality, 3-acceptable, 4-good, 5-excellent. A
      total of 128 (54.7 %) patients were scanned in a scoop stretcher and 106 (45.3 %)
      were scanned without, 183 males and 51 females (average age, 46 (16-94) years;
      SD, 20). The average quality grading for the patients scanned in the scoop was
      4.64 compared to 4.68 in those without the scoop. There was no significant
      grading difference between the groups, consultant (p = 0.096) and trainees (p =
      0.782). No artefacts were attributable to the scoop stretcher 0/128 (0 %).
      Following our experience, the use of scoop stretchers is recommended for
      efficient, safe and practical management of trauma patients and in terms of
      imaging, with no detrimental effect on image quality.

PMID- 23978870
TI  - Ultrasound-guided regional anesthesia: learning with an optimized cadaver model.
AB  - PURPOSE: To date, there have been few studies of the simulation of ultrasound
      guided regional anesthesia for teaching purposes. The present study aimed to
      evaluate the visibility of nerves and their adjacent structures, and the
      feasibility of the use of ultrasound-guided blocks in specially prepared cadavers
      to develop a new teaching model. METHODS: Nerves of the brachial, lumbar, and
      sacral plexus were examined, and their visibility evaluated in 12 specially
      embalmed cadavers. Thereafter a needle was advanced under direct ultrasound
      guidance to target nerves, and selected blocks were imitated using saline. The
      model was evaluated with standardized questionnaires in two international
      workshops with 124 participants. RESULTS: The selected nerves were successfully
      identified in all cadavers. The typical ultrasound appearance of nerves and their
      adjacent structures was very similar to the echotexture of the living, and the
      spread of injected saline around nerves was comparable to that of local
      anesthetics used in live patients. 79 % of the participants completed the
      questionnaire and confirmed the value of this optimized teaching model.
      CONCLUSIONS: This cadaver model is a promising teaching tool for practicing both
      the visualization of nerves and the needle manipulation. Moreover, it is possible
      to simulate the interventional application and the spread of local anesthetics
      using saline. With the aim of maximizing the effectiveness of teaching, it is
      hoped that we, and others, may be able to establish the use of this kind of tool
      as a valuable adjunct to other models of teaching regional anesthesia.

PMID- 23978871
TI  - Comparison of mesiodistal space measurements of single-implant sites on panoramic
      and oblique images generated by cone-beam CT.
AB  - PURPOSE: To compare the mesiodistal space measurements of single-implant sites on
      panoramic and oblique images generated by cone-beam CT (CBCT). METHODS: CBCT
      images for 101 single-implant sites of 66 patients referred for pre-surgical
      radiographic implant planning were selected for the study; 15-mm-thickness
      panoramic images were reformatted and used for measuring mesiodistal space
      dimensions. The measurements were repeated and compared with those of thin
      oblique images (200-300 MU) using Wilcoxon signed rank test. The correlation
      between measurements in addition to intra-observer agreement was evaluated by
      Pearson's correlation coefficients. RESULTS: All mesiodistal space measurements
      on panoramic and oblique images generated by CBCT were strongly correlated and
      there were no statistically significant differences between them (P < 0.05).
      CONCLUSIONS: Both panoramic and oblique images generated by CBCT can be used for
      measuring mesiodistal space dimensions of single-implant sites.

PMID- 23978872
TI  - Ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy: a
      randomized controlled trial.
AB  - PURPOSE: To test the efficacy and safety of ursodeoxycholic acid (UDCA) in the
      treatment of patients with intrahepatic cholestasis of pregnancy (ICP). METHODS:
      In the randomized (double-blind, placebo-controlled) study 20 pregnant women with
      ICP received (random allocation of) either 450 mg/day UDCA or placebo for 14 days
      during the third trimester of pregnancy. The severity of pruritus was registered
      and itching scores were assessed before the treatment and weekly thereafter. The
      effects of UDCA on liver function and fetoplacental hormone production were
      measured with covering laboratory testing: serum levels of alanine
      aminotransferase (ALAT), total bile acids (TBA), estradiol, progesterone,
      prolactin, cholesterol, HDL-cholesterol, triglycerides, activated partial
      thromboplastin time, fibrinogen D-dimers (FIDD) and platelet count were assessed
      before the treatment and weekly thereafter. Data on pregnancy and delivery
      outcome were recorded and analyzed. RESULTS: UDCA was well tolerated. A
      significant improvement in itching scores was detected in 2 weeks in the group
      receiving UDCA. Serum levels of ALAT and TBA fell after 2 weeks treatment. The
      other laboratory values were not modified by the treatment. CONCLUSIONS: UDCA
      improves maternal itching scores and liver function tests without interfering
      with the fetoplacental estrogen production in patients with ICP. UDCA is well
      tolerated by pregnant women. No fetal or neonatal side-effects could be detected.

PMID- 23978873
TI  - Increased osteopontin expression is associated with progression from vulvar
      precancerous lesions to vulvar squamous cell carcinoma.
AB  - PURPOSE: Vulvar squamous cell carcinoma (VSCC) contributes to about 3-5% of all
      gynecological cancers. Vulvar intraepithelial neoplasia (VIN) and vulvar lichen
      sclerosus (VLS) are regarded as precancerous lesions. Early detection and
      treatment of precancerous lesions may prevent development of VSCC. Osteopontin
      (OPN) has been shown to be involved in many physiological and pathological
      processes, such as tumor progression, by promoting cancer cell invasion and
      metastasis. As a result of these findings, OPN has been described as a potential
      marker for tumor progression in some malignancies. In this study, we investigated
      the expression of OPN in vulvar tissue specimens and compared its expression
      between different histopathological grades. METHODS: In the present study, the
      expression patterns of OPN in 80 paraffin-embedded tissue specimens, including 25
      VSCC samples, 21 VIN lesions and 21 VLS, in addition to 13 normal vulvar samples,
      were examined by the immunohistochemical method and chromogenic in situ
      hybridization. RESULTS: The intensity of OPN expression steadily increased
      according to the pathological grades. In addition, OPN staining was found in the
      extracellular matrix in VSCC. CONCLUSIONS: Expression levels of OPN increased
      from VLS and VIN to VSCC, and steadily increased with the pathological stage of
      VSCC. Our results suggest that OPN may be associated with the progression of
      VSCC.

PMID- 23978877
TI  - Current world literature. Obesity and nutrition.

PMID- 23978876
TI  - Gremlin-1 associates with fibrillin microfibrils in vivo and regulates
      mesothelioma cell survival through transcription factor slug.
AB  - Malignant mesothelioma is a form of cancer that is highly resistant to
      conventional cancer therapy for which no major therapeutic advances have been
      introduced. Here, we identify gremlin-1, a known bone morphogenetic protein
      inhibitor crucial for embryonic development, as a potential therapeutic target
      for mesothelioma. We found high expression levels of gremlin-1 in the
      mesothelioma tumor tissue, as well as in primary mesothelioma cells cultured from
      pleural effusion samples. Downregulation of gremlin-1 expression by siRNA
      mediated silencing in a mesothelioma cell line inhibited cell proliferation. This
      was associated with downregulation of the transcription factor slug as well as
      mesenchymal proteins linked to cancer epithelial-to-mesenchymal transition.
      Further, resistance to paclitaxel-induced cell death was associated with high
      gremlin-1 and slug expression. Treatment of gremlin-1-silenced mesothelioma cells
      with paclitaxel or pemetrexed resulted in efficient loss of cell survival.
      Finally, our data suggest that concomitant upregulation of fibrillin-2 in
      mesothelioma provides a mechanism for extracellular localization of gremlin-1 to
      the tumor microenvironment. This was supported by the demonstration of
      interactions between gremlin-1, and fibrillin-1 and -2 peptides as well as by
      colocalization of gremlin-1 to fibrillin microfibrils in cells and tumor tissue
      samples. Our data suggest that gremlin-1 is also a potential target for
      overcoming drug resistance in mesothelioma. 

PMID- 23978880
TI  - Present and future.

PMID- 23978879
TI  - The HIPAA conundrum in the era of mobile health and communications.

PMID- 23978881
TI  - Clinical approach to children with suspected neurodegenerative disorders.
AB  - Inherited neurodegenerative disorders are common in the Kingdom of Saudi Arabia
      as a result of the high rate of consanguinity. This is a complex field with a
      multitude of different disorders characterized by a variety of clinical
      manifestations, complex molecular biology, and a long list of potential
      investigations. As a result, this is often a confusing and difficult area for non
      specialists, resulting in delays in reaching the diagnosis. Reaching a specific
      diagnosis is of clear importance for providing appropriate therapy, prognosis,
      and genetic counseling. This paper is intended to provide a simplified practical
      approach to guide residents and generalists in the initial diagnostic evaluation
      of children with suspected neurodegenerative disorders. Emphasis is placed on
      useful clinical signs, diagnostic tips, potential pitfalls, and recent advances
      in therapy. 

PMID- 23978882
TI  - Recombinant tissue plasminogen activator for acute ischemic stroke.
AB  - Stroke is a leading cause of serious and long-term disability and death worlwide,
      with approximately 750,000 strokes occuring annually in the United States of
      America. The risk of stroke doubles each decade for people over 55 years.
      Cerebral angiography conducted soon after the onset of stroke demonstrates
      arterial occlusion in 70%-80% of cases. Recanalization of an occluded cerebral
      artery may assist in the recovery of reversibly ischemic tissue and limit the
      neurological disability. In June 1996, the recombinant tissue plasminogen
      activator was approved as a safe and an effective intravenous treatment for acute
      ischemic stroke, especially if given within 3 hours of onset of symptoms. Since
      approval, less than 5% of all stroke patients are receiving recombinant tissue
      plasminogen activator. In this review we try to answer the question of whether
      recombinant tissue plasminogen activator therapy should be the first-line
      treatment for acute ischemic stroke. The result of major recombinant tissue
      plasminogen activator trials will be summarized and reviewed critically. 

PMID- 23978883
TI  - Brachial plexus impairment: Incidence and predisposing factors.
AB  - OBJECTIVE: To study brachial plexus impairment, incidence and predisposing
      factors. METHODS: A retrospective study of cases of brachial plexus palsy
      diagnosed post delivery at Al-Jamahiria Maternity Teaching Hospital, Benghazi,
      Libya from 1st January 1993 to 1st December 1993. RESULTS: Out of a total of
      17,288 deliveries in 1993, there were 20 cases of brachial plexus impairment
      (0.115% or 1.15/1000 births). The predisposing factors were maternal age >24
      years (85%), increased parity (100%), obesity (35%), diabetes mellitus (20%),
      term infant (100%), birth weight of >/= 4 kg, attending juniors and midwives
      (75%). CONCLUSION: Maternal age >24 years, increased parity, obesity, diabetes
      mellitus, term infants, birth weight >/= 4 kg and an attendant of little
      experience were the most valuable risk factors predisposing to brachial plexus
      palsy at birth. We conclude that birth control and glucose controls are very
      important for prevention, though cesarean delivery can be performed for at risk
      mothers. Serial training programs on the management of obstetric emergencies,
      such as shoulder dystocia, are essential for the junior doctors and midwives.

PMID- 23978884
TI  - Vigabatrin versus ACTH in the treatment of infantile spasms.
AB  - OBJECTIVE: To compare adrenocorticotropic hormone with vigabatrin as a single
      mono-therapy for infantile spasms. We studied hospitalization time, clinical
      response, whether complete or partial, time taken for improvement, and presence
      or absence of recurrence after stopping the medication. Together with improvement
      of electroencephalographic changes, and time taken for significant response,
      neurodevelopmental and cognitive responses in both groups. METHODS: Our study was
      conducted initially on 36 patients. They were divided randomly into 2 groups. The
      first group received adrenocorticotropic hormone and 2nd vigabatrin, as a single
      mono-therapy for infantile spasms. There was a male sex predominance of (1.25:1),
      with 20 males to 16 females affected. The mean age of onset was 5.2 months. Of
      the 36 patients, 26 patients (72.2%) were having typical hypsarrhythmia on
      electroencephalogram and 10 (27.8%) had burst suppression pattern. All 36
      patients were having typical spasms. Four patients, all female, were excluded
      from the study, as their families lived outside Riyadh, and they were not regular
      on follow up. The remaining 32 patients continued the study. therefore, 16
      patients were put in each group randomly. RESULTS: In the first group
      (adrenocorticotropic hormone group): initial improvement was achieved in 10
      infants (62.5%), with median response time of 9 days, at a dose of 20 IU
      intramuscular daily, in the first 10 days. In the 2nd group vigabatrin: the
      initial improvement was achieved at 4 days in 9 infants (56.25%) at an average
      dose of 87mg/kg /day. The response was more appreciated in the secondary group
      infantile spasms with a known etiology. Side effects were noted in younger age
      group (5 months or below); 14 patients (78.5%) out of 16 suffered side effects
      from the adrenocorticotropic hormone group. Side effects in the vigabatrin group
      were much less, only 4 patients (25%) had some drowsiness, none had visual
      disturbances. CONCLUSION: Vigabatrin is an effective therapy for infantile
      spasms. It has shown to be as effective as adrenocorticotropic hormone, with less
      hospital dependency and milder side effects. As far as this study is concerned,
      differences in neurodevelopmental outcome are probably due to the underlying
      etiology. More research may be needed to further enhance the effects on both
      cognitive function and vision.

PMID- 23978885
TI  - Outcome of thymectomy in patients with Myasthenia Gravis.
AB  - OBJECTIVE: Myasthenia Gravis is a neuromuscular disorder characterized by
      weakness and fatigability of skeletal muscles. Thymectomy is now beneficial even
      for non-thymomatous patients. The aim of this paper is to evaluate the role of
      thymectomy as on the treatment options for myasthenia gravis. METHODS: Thirty
      patients underwent thymectomy in the period from April 1999 through to July 2000.
      They were collected from different teaching hospitals in Baghdad, Iraq. All these
      cases were studied conventionally including history, physical and neurological
      examination in addition to investigations with particular emphasis on connective
      tissue screen and thyroid function test. RESULTS: The age in this study ranged
      between 17-55 years. The preoperative duration ranged between 2-20 months and the
      postoperative follow up period ranged between 6 months-14 years. The most
      favorable results were obtained in patients without thymoma with short duration.
      CONCLUSION: Early thymectomy carries the best results in Myasthenia Gravis and
      every effort should be made to shorten the preoperative duration for both
      thymomatous and nonthymomatous patients. Patients with symptoms can be better
      controlled with anticholinesterase drugs than patients using steroid and
      cytotoxic drugs. Thymectomy is beneficial for most patients with Myasthenia
      Gravis and especially in those with benign folicular hyperplasia.

PMID- 23978886
TI  - Craniopharyngioma: Analysis of factors that affect the outcome.
AB  - OBJECTIVE: The aim of this work is to find out factors that affect the outcome of
      treatment of patients with craniopharyngioma treated at King Khalid University
      Hospital, Riyadh, Kingdom of Saudi Arabia. METHODS: This study was carried out
      retrospectively by reviewing the medical records of all patients with
      craniopharyngiomas treated at King Khalid University Hospital, Riyadh, Kingdom of
      Saudi Arabia in the last 10 years (January 1990 through to December 1999), and
      collecting clinical, radiological, surgical, and follow-up data and performing
      statistical analysis to find out factors that affect the outcome of such cases.
      RESULTS: There were 11 females (61%), and 7 males (39%), the median age was 24
      years. The main presenting symptoms were reduced vision in 66.7%, symptoms of
      raised intracranial pressure in 50%, endocrinal problems in 33.3%, seizures in
      16.7%, and hemiparesis in 5.6%. Radiologic studies showed 72% of tumors had mixed
      solid and cystic components, calcification in 83%, and ventricular dilatation in
      50% of cases. The tumor extended to the posterior fossa in 11%, and to both
      middle and posterior fossae in 11% of cases. Eighty-nine percent of patients had
      tumor excision through pterional craniotomy and 11% through subfrontal approach.
      Gross total removal was achieved in 17% and subtotal resection in 83%. Tumor
      recurred in 9 patients (50%), 4 of them (44%) had postoperative radiotherapy. The
      outcome was good in 10 patients (56%), poor in 6 patients (33%), and 2 patients
      died (11%). The patient age, radiological appearance of tumors and their location
      were significantly correlated with the outcome (p 0.02, 0.02, 0.04). CONCLUSION:
      Craniopharyngiomas are a common tumor in children. Ophthalmologists and
      Pediatricians should be aware of the clinical presentation and refer patients to
      specialized centers for treatment. Total resection of the tumor should be the
      goal of the Neurosurgeon as it offers the best chance of cure.

PMID- 23978887
TI  - Quality of referral letters to Abha Psychiatric Hospital, Asir region, Kingdom of
      Saudi Arabia.
AB  - OBJECTIVE: This study aims to explore the quality of referral letters from
      different health institutions to Abha Psychiatric Hospital, the only psychiatric
      center in Asir region, Kingdom of Saudi Arabia. METHODS: In this descriptive
      study, a total of 582 consecutive referral letters to Abha Psychiatric Hospital,
      during the first half of 1998, were evaluated for the components that are
      supposed to be found in the consentient referral letter to a psychiatric service.
      Each letter quality was indicated as good or poor according to the used scale.
      RESULTS: Thirty-six percent of the referral letters were poor. The clinical
      information relating to the psychiatric history was significantly poor compared
      to other clinical information (p<0.05). Asir Central Hospital (tertiary level)
      referral letters were better in quality than those of secondary hospitals
      (p<0.001). Referral letters with diagnosis or impression of legal concern showed
      a better quality compared to others (p<0.001). CONCLUSION: The quality of
      clinical information relating to the psychiatric history in the referral letters
      to psychiatric service, needs to be improved to ensure better patient care and
      more appropriate use of resources.

PMID- 23978888
TI  - Psychiatric admission in a general hospital: Patients profile and patterns of
      service utilization over a decade.
AB  - OBJECTIVE: To analyze the socio-demographic and clinical characteristics of
      admitted patients and the patterns of their service utilization over a decade
      from March 1988 to March 1998. METHODS: Prospective data compilation using a
      structured questionnaire, hospital records and follow-up observations at King
      Fahd Hospital of the University in Al-Khobar, Kingdom of Saudi Arabia. RESULTS: A
      total of 1366 patients (683 of each sex) had 2217 admissions in 10 years. By the
      International Classification of Diseases, 10th edition criteria, 19.5% had
      schizophrenia, 15.2% bipolar disorder, 9.9% depressive episodes, 8.6% acute and
      transient psychotic disorders, 7.7% adjustment disorders and 7.6% dissociative
      disorders. Males were more frequently admitted for schizophrenia and females for
      mood and anxiety disorders. Most non-Arab expatriates were diagnosed as acute and
      transient psychotic, stress-related or dissociative disorders. Re
      hospitalizations constituted 28% of all admissions. The mean length of stay was
      25 days per admission and 41 days per patient. The overall bed occupancy rate was
      84.9%. A subgroup of 16.9% of patients, mostly with schizophrenia or bipolar
      disorder, consumed 62.3% of the bed occupancy. CONCLUSION: Gender and immigration
      were the main determinants of variance in patient characteristics, nosological
      distribution and pattern of service use. More beds are needed. Psycho-educational
      programs should be intensified to reduce the social stigma and societal
      intolerance to mental patients. Active family involvement improves compliance and
      might reduce re-hospitalization rates. Heavy service consumers should be
      transferred to long-stay facilities.

PMID- 23978889
TI  - Weather and the first episode of schizophrenia.
AB  - OBJECTIVE: To emphasize the effect of weather on the occurrence of the first
      episode of Schizophrenia. METHODS: The relationship between weather and the first
      episode of schizophrenia was investigated at Ibn Sina Psychiatric Hospital,
      Damascus, Syria, from 1997 to 1999. RESULTS: Schizophrenia in developing
      countries affects men at a higher rate than women. The highest rates are found in
      lower socioeconomic classes, and the first episode of the disease usually occurs
      in May or June, and after weather changes. CONCLUSION: High temperature (equal or
      exceeding body temperature) is considered one of the outside factors of
      schizophrenia, however, as yet the etiology of the disease is still unknown.

PMID- 23978890
TI  - Sociodemographic and clinical characteristics of possessive disorder in Jordan.
AB  - OBJECTIVE: To study the sociodemographic and clinical characteristics of
      possessive disorder in Jordan. METHODS: This study was carried out prospectively
      at Prince Rashid Ben Al-Hassan Hospital, Irbid, Jordan between January 1997 and
      December 2000. It included all psychiatric patients who presented to the
      psychiatric outpatient clinic with a mono-symptom of being possessed or
      influenced by the Jinn, a total of 179 patients were studied. RESULTS: Possessive
      disorder is more common among males (111) than females (68) with a male:female
      ratio of 1.6:1. With a mean age of 23.15 years and standard deviation of 6.93,
      the majority (82.1%) of patients were young of low educational attainment from
      rural areas (67.6%). The mean duration of illness was 24.61 months (standard
      deviation of 10.64) and the most common site of possession was head and neck
      (19.6%) followed by chest (11.7%) and upper limbs (11.7%). The most common mode
      of perception was somatic both visual and auditory (25.7%) and the most common
      behavioral changes induced by the possessing agent were loss of control (17.3%)
      followed by abnormal movement (16.6%), pseudo seizure (15.6%), loss of
      consciousness (14%) and change in tone of voice (14%). Sixty-eight (38%) of the
      patients had history of sexual intercourse with the possessing agent, more males
      (53) than females (15) had such experience. Two thirds of the patients had single
      possessing agent and almost all patients had been treated by native healers and
      about 2 thirds of the patients had reported psychosocial stresses prior to the
      onset of their illness. CONCLUSION: Possessive disorder is a common condition in
      clinical practice that poses a diagnostic problem, it affects young males of low
      educational attainment from rural areas. Education and awareness is needed to
      prevent improper traditional therapy that may negatively affect the prognosis of
      this disorder.

PMID- 23978891
TI  - Accidental tricyclic antidepressant poisoning in a 2 year-old boy.
AB  - We present a 2-year old boy with accidental ingestion of a tricyclic
      antidepressant and outline the clinical features, management and prevention.
      Despite ingesting a high dose of amitriptyline (20mg/kg) and showing serum levels
      above the toxic range (1380 ng/ml), our patient did not develop any life
      threatening complications. Gastric lavage followed by instillation of activated
      charcoal, repeated at 6 hours, along with supportive measures led to complete
      recovery in 48 hours. As children are often exposed to tricyclic antidepressant
      poisoning, their carers and physicians need to be well aware of the disorder and
      its management. 

PMID- 23978892
TI  - Insidious onset of grade IV intraventricular hemorrhage in a premature infant. A
      case of clinical deception.

PMID- 23978893
TI  - Erratum: A comparison between Walsh and autoregressive derived parameters of
      heart rate variability spectra in normal subjects and diabetics.

PMID- 23978894
TI  - Potential savings by reduced CD4 monitoring in stable patients with HIV receiving
      antiretroviral therapy.

PMID- 23978895
TI  - Hepatoprotective properties of the Indian gooseberry (Emblica officinalis
      Gaertn): a review.
AB  - Liver diseases characterized by inflammation or tissue damage affect the optimal
      functioning and increase the morbidity and mortality of the affected individual.
      Liver diseases are a largely neglected health issue and recent reports indicate
      that they affect over 10% of the world population, with the highest burden in low
      and middle income countries that have minimal medical resources. To complicate
      matters the currently available pharmacological therapies are not optimal and
      when used for extended periods of time impart systemic toxicity. Diet can modify
      pathophysiological processes, including those of hepatotoxins, and studies have
      shown that some dietary constituents can afford heptoprotection. Emblica
      officinalis Gaertn or Phyllanthus emblica Linn, commonly known as the Indian
      gooseberry in English or amla in Hindi, is one of the most important medicinal
      and dietary plants in the Indian subcontinent. The fruits are of dietary and
      medicinal use and have wide applications in both traditional and folk systems of
      medicine. Scientific studies have shown amla to be effective in
      preventing/ameliorating the toxic effects of hepatotoxic agents like ethanol,
      paracetamol, carbon tetrachloride, heavy metals, ochratoxins,
      hexachlorocyclohexane, antitubercular drugs and hepatotoxicity resulting from
      iron overload. Amla is also reported to impart beneficial effects on liver
      function and to mitigate hyperlipidemia and metabolic syndrome. Amla possesses
      protective effects against chemical-induced hepatocarcinogenesis in animal models
      of study. Additionally, the phytochemicals quercetin, gallic acid, corilagin and
      ellagic acid are also reported to protect against the cytotoxic effects of
      paracetamol, microcystins, galactosamine and lipopolysaccharide. The
      hepatoprotective actions of amla appear to be mediated by its free radical
      scavenging, antioxidant, anti-inflammatory and modulation of the xenobiotic
      detoxification process and lipid metabolism. 

PMID- 23978896
TI  - Minutes of the Annual Business Meeting of the members of the Behavior Genetics
      Association: Monday, July 1, 2013, 12:20-1:40, Amphi Sciences Naturelles,
      Marseille, France.

PMID- 23978898
TI  - Privacy by design in personal health monitoring.
AB  - The concept of privacy by design is becoming increasingly popular among
      regulators of information and communications technologies. This paper aims at
      analysing and discussing the ethical implications of this concept for personal
      health monitoring. I assume a privacy theory of restricted access and limited
      control. On the basis of this theory, I suggest a version of the concept of
      privacy by design that constitutes a middle road between what I call broad
      privacy by design and narrow privacy by design. The key feature of this approach
      is that it attempts to balance automated privacy protection and autonomously
      chosen privacy protection in a way that is context-sensitive. In personal health
      monitoring, this approach implies that in some contexts like medication
      assistance and monitoring of specific health parameters one single automatic
      option is legitimate, while in some other contexts, for example monitoring in
      which relatives are receivers of health-relevant information rather than health
      care professionals, a multi-choice approach stressing autonomy is warranted. 

PMID- 23978897
TI  - Association between autozygosity and major depression: stratification due to
      religious assortment.
AB  - The effects of inbreeding on the health of offspring can be studied by measuring
      genome-wide autozygosity as the proportion of the genome in runs of homozygosity
      (F roh) and relate F roh to outcomes such as psychiatric phenotypes. To
      successfully conduct these studies, the main patterns of variation for genome
      wide autozygosity between and within populations should be well understood and
      accounted for. Within population variation was investigated in the Dutch
      population by comparing autozygosity between religious and non-religious groups.
      The Netherlands have a history of societal segregation and assortment based on
      religious affiliation, which may have increased parental relatedness within
      religious groups. Religion has been associated with several psychiatric
      phenotypes, such as major depressive disorder (MDD). We investigated whether
      there is an association between autozygosity and MDD, and the extent to which
      this association can be explained by religious affiliation. All F roh analyses
      included adjustment for ancestry-informative principal components (PCs) and
      geographic factors. Religious affiliation was significantly associated with
      autozygosity, showing that F roh has the ability to capture within population
      differences that are not captured by ancestry-informative PCs or geographic
      factors. The non-religious group had significantly lower F roh values and
      significantly more MDD cases, leading to a nominally significant negative
      association between autozygosity and depression. After accounting for religious
      affiliation, MDD was not associated with F roh, indicating that the relation
      between MDD and inbreeding was due to stratification. This study shows how past
      religious assortment and recent secularization can have genetic consequences in a
      relatively small country. This warrants accounting for the historical social
      context and its effects on genetic variation in association studies on
      psychiatric and other related traits. 

PMID- 23978899
TI  - Quo vadis, Kras?

PMID- 23978900
TI  - Multicentric histiocytosis related to avian leukosis virus subgroup J (ALV-J)
      infection in meat-type local chickens.
AB  - Gross lesions characterized by swollen livers and spleens accompanied by diffuse
      white miliary spots, which resembled those of Marek's disease, were detected in
      two flocks of local meat-type chickens at a Japanese poultry processing plant in
      June and August 2010. The microscopic examinations revealed proliferative foci
      consisting of spindle or polymorphic cells in the interstitium of livers, splenic
      follicles and the interstitium of kidneys. These cells were positive
      immunohistochemically with Iba1 antibody, indicating they were histiocytic cells.
      Some of them contained antigens of avian leukosis virus (ALV) by
      immunohistochemistry,and the env gene of ALV subgroup J was detected from the
      spleens by polymerase chain reaction (PCR). Phylogenetic analysis of the PCR
      product indicated that the env gene might be descended from the American ADOL
      7501 strain of ALV-J. These results suggest that the swollen livers and spleens
      of the meat-type chickens may come from histiocytic proliferation caused by ALV-J
      infection. 

PMID- 23978901
TI  - Live cell imaging of alphaherpes virus anterograde transport and spread.
AB  - Advances in live cell fluorescence microscopy techniques, as well as the
      construction of recombinant viral strains that express fluorescent fusion
      proteins have enabled real-time visualization of transport and spread of
      alphaherpes virus infection of neurons. The utility of novel fluorescent fusion
      proteins to viral membrane, tegument, and capsids, in conjunction with live cell
      imaging, identified viral particle assemblies undergoing transport within axons.
      Similar tools have been successfully employed for analyses of cell-cell spread of
      viral particles to quantify the number and diversity of virions transmitted
      between cells. Importantly, the techniques of live cell imaging of anterograde
      transport and spread produce a wealth of information including particle transport
      velocities, distributions of particles, and temporal analyses of protein
      localization. Alongside classical viral genetic techniques, these methodologies
      have provided critical insights into important mechanistic questions. In this
      article we describe in detail the imaging methods that were developed to answer
      basic questions of alphaherpes virus transport and spread.

PMID- 23978902
TI  - A screen-printed endotoxin sensor based on amperometry using a novel p
      aminophenol conjugated substrate for a Limulus amebocyte lysate protease
      reaction.
AB  - We developed a novel protease detection method based on amperometry using a p
      aminophenol (pAP) conjugated substrate. We prepared Boc-Leu-Gly-Arg-pAP (LGR-pAP)
      as a novel substrate for a clotting enzyme, which is a protease activated by an
      endotoxin-induced Limulus amebocyte lysate (LAL) cascade reaction. The basic
      study using cyclic voltammetry revealed that the oxidation peak potentials of LGR
      pAP and pAP were sufficiently separated from each other (0.25 V) to conduct
      amperometric detection of protease activity. We combined simple amperometric
      detection with a screen-printed electrode chip to produce a practical protease
      sensor. As an application of the sensor, we demonstrated quantitative endotoxin
      sensing. The endotoxin activated zymogens contained in the LAL to generate pAP,
      which was then electrochemically detected by potential step chronoamperometry
      (PSCA). The observed oxidation current increased with the concentration of
      endotoxin in the LAL assay solution. This PSCA detection was performed with a
      disposable chip sensor consisting of a screen-printed electrode and a fluidic
      channel with a hydrophilic cover. This chip sensor successfully detected 10-1000
      EU L(-1) endotoxin within 60 min. This novel amperometric measurement with a
      screen-printed electrode not only provides compact, low-cost, and easy-to-use
      sensors for on-site monitoring of endotoxin, but also shows promise for use in
      other in vitro protease assays for biochemical research, diagnosis, and drug
      development. 

PMID- 23978903
TI  - The transfer of analytical procedures.
AB  - Analytical method transfers are certainly among the most discussed topics in the
      GMP regulated sector. However, they are surprisingly little regulated in detail.
      General information is provided by USP, WHO, and ISPE in particular. Most
      recently, the EU emphasized the importance of analytical transfer by including it
      in their draft of the revised GMP Guideline. In this article, an overview and
      comparison of these guidelines is provided. The key to success for method
      transfers is the excellent communication between sending and receiving unit. In
      order to facilitate this communication, procedures, flow charts and checklists
      for responsibilities, success factors, transfer categories, the transfer plan and
      report, strategies in case of failed transfers, tables with acceptance limits are
      provided here, together with a comprehensive glossary. Potential pitfalls are
      described such that they can be avoided. In order to assure an efficient and
      sustainable transfer of analytical procedures, a practically relevant and
      scientifically sound evaluation with corresponding acceptance criteria is
      crucial. Various strategies and statistical tools such as significance tests,
      absolute acceptance criteria, and equivalence tests are thoroughly descibed and
      compared in detail giving examples. Significance tests should be avoided. The
      success criterion is not statistical significance, but rather analytical
      relevance. Depending on a risk assessment of the analytical procedure in
      question, statistical equivalence tests are recommended, because they include
      both, a practically relevant acceptance limit and a direct control of the
      statistical risks. However, for lower risk procedures, a simple comparison of the
      transfer performance parameters to absolute limits is also regarded as
      sufficient. 

PMID- 23978904
TI  - Investigation of bone conditions for orthodontic anchorage plates in the anterior
      mandible.
AB  - OBJECTIVES: The clinical success of orthodontic anchorage plates depends on the
      stability of the miniscrews used for fixation. For good stability, the
      application site must provide bone of good quantity and quality. This study was
      performed to analyze bone quantity for orthodontic anchorage plates in the
      anterior mandible. PATIENTS AND METHODS: A total of 51 computed tomography (CT)
      scans of fully dentate patients (mean age 24.0+/-8.1 years; 27 men and 24 women)
      were evaluated. Measurements were taken to analyze the total orovestibular and
      vestibular cortical thickness of the mandibular jawbone at different anterior
      locations and levels. RESULTS: Vestibular cortical thickness is generally
      thinnest within the incisor area on the apex level. Its thickness increases in
      basal and distal directions. The total orovestibular thickness is also the least
      on the level of the anterior mandibular apices, becoming thicker toward more
      basal levels and the posterior teeth. CONCLUSION: We can reasonably assume that
      the stability of anchorage plates can be optimized by selecting a position well
      basal to the apices of the lower incisors, as this area offers enhanced cortical
      and total jawbone thickness.

PMID- 23978905
TI  - Correlation between spin structure oscillations and domain wall velocities.
AB  - Magnetic sensing and logic devices based on the motion of magnetic domain walls
      rely on the precise and deterministic control of the position and the velocity of
      individual magnetic domain walls in curved nanowires. Varying domain wall
      velocities have been predicted to result from intrinsic effects such as
      oscillating domain wall spin structure transformations and extrinsic pinning due
      to imperfections. Here we use direct dynamic imaging of the nanoscale spin
      structure that allows us for the first time to directly check these predictions.
      We find a new regime of oscillating domain wall motion even below the Walker
      breakdown correlated with periodic spin structure changes. We show that the
      extrinsic pinning from imperfections in the nanowire only affects slow domain
      walls and we identify the magnetostatic energy, which scales with the domain wall
      velocity, as the energy reservoir for the domain wall to overcome the local
      pinning potential landscape. 

PMID- 23978906
TI  - Modeling brain function: current developments and future prospects.
AB  - We discuss work aimed at building functional models of the whole brain
      implemented in large-scale simulations of millions of individual neurons. Recent
      developments in this area demonstrate that such models can explain a variety of
      behavioral, neurophysiological, and neuroanatomical data.We argue that these
      models hold the potential to expand our understanding of the brain by connecting
      these levels of analysis in new and informative ways. However, current modeling
      efforts fall short of the target of whole-brain modeling. Consequently,we discuss
      different avenues of research that continue to progress toward that distant, but
      achievable, goal.

PMID- 23978907
TI  - Chronic psychosocial stress causes delayed extinction and exacerbates
      reinstatement of ethanol-induced conditioned place preference in mice.
AB  - RATIONALE: We have shown previously, using an animal model of voluntary ethanol
      intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to
      chronic psychosocial stress induces increased ethanol intake and EtOH-CPP
      acquisition in mice. OBJECTIVE: Here, we examined the impact of chronic
      subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol
      induced reinstatement of CPP. METHODS: Mice were conditioned with saline or 1.5
      g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the
      mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was
      assessed during seven daily trials without ethanol injection. In the second
      experiment and after the EtOH-CPP test, the mice were subjected to 7 days of
      extinction trials before the 19 days of chronic stress. Drug-induced EtOH-CPP
      reinstatement was induced by a priming injection of 0.5 g/kg ethanol. RESULTS:
      Compared to the single-housed colony mice, CSC mice exhibited increased anxiety
      like behavior in the elevated plus maze (EPM) and the open field tests.
      Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly,
      CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior.
      CONCLUSION: Taken together, this study indicates that chronic psychosocial stress
      can have long-term effects on EtOH-CPP extinction as well as drug-induced
      reinstatement behavior and may provide a suitable model to study the latent
      effects of chronic psychosocial stress on extinction and relapse to drug abuse.

PMID- 23978908
TI  - Hindbrain orexin 1 receptors influence palatable food intake, operant responding
      for food, and food-conditioned place preference in rats.
AB  - RATIONALE: Brain orexin 1 receptors (OX1Rs) are involved in food-motivated
      behavior. Most research has focused on forebrain OX1R populations, but hindbrain
      OX1Rs affect feeding. We hypothesized that hindbrain OX1Rs affect the reward
      value of food. OBJECTIVES: We examined the effects of hindbrain OX1R stimulation
      or blockade on motivation for food, palatable high-fat (HF) food intake, and food
      conditioned place preference. METHODS: Rats trained to lever press for sucrose on
      a progressive ratio (PR) schedule received fourth intracerebroventricular (icv)
      injections of vehicle, orexin-A (0.1-1 nmol), or the OX1R antagonist SB334867 (10
      20 nmol) before operant test sessions. Effects of these treatments on HF food
      intake during daily 1-h tests were assessed with fourth icv and nucleus of the
      solitary tract (NTS) injections. We conditioned a place preference by pairing HF
      food with one side of a two-sided chamber and then examined the effect of 20 nmol
      fourth icv SB334867 on the expression of that preference. RESULTS: In ad lib fed
      rats on the PR schedule, fourth icv orexin-A significantly increased responding
      and breakpoint relative to the vehicle. In 24-h food-deprived rats, fourth icv
      SB334867 significantly decreased responding and breakpoint. Orexin-A delivered to
      the fourth ventricle (0.1 nmol) or NTS (0.01 nmol) increased HF diet intake.
      Fourth icv SB334867 did not affect HF food intake, but SB334867 delivered either
      fourth icv (20 nmol) or intra-NTS (5-10 nmol) suppressed chow intake. Expression
      of HF food-conditioned place preference was inhibited by fourth icv SB334867.
      CONCLUSIONS: Hindbrain OX1R activity affects food-motivated operant behavior and
      may play a role in responding to cues that predict palatable food.

PMID- 23978909
TI  - Acute electronic cigarette use: nicotine delivery and subjective effects in
      regular users.
AB  - RATIONALE: Electronic cigarettes are becoming increasingly popular among smokers
      worldwide. Commonly reported reasons for use include the following: to quit
      smoking, to avoid relapse, to reduce urge to smoke, or as a perceived lower-risk
      alternative to smoking. Few studies, however, have explored whether electronic
      cigarettes (e-cigarettes) deliver measurable levels of nicotine to the blood.
      OBJECTIVE: This study aims to explore in experienced users the effect of using an
      18-mg/ml nicotine first-generation e-cigarette on blood nicotine, tobacco
      withdrawal symptoms, and urge to smoke. METHODS: Fourteen regular e-cigarette
      users (three females), who are abstinent from smoking and e-cigarette use for 12
      h, each completed a 2.5 h testing session. Blood was sampled, and questionnaires
      were completed (tobacco-related withdrawal symptoms, urge to smoke, positive and
      negative subjective effects) at four stages: baseline, 10 puffs, 60 min of ad lib
      use and a 60-min rest period. RESULTS: Complete sets of blood were obtained from
      seven participants. Plasma nicotine concentration rose significantly from a mean
      of 0.74 ng/ml at baseline to 6.77 ng/ml 10 min after 10 puffs, reaching a mean
      maximum of 13.91 ng/ml by the end of the ad lib puffing period. Tobacco-related
      withdrawal symptoms and urge to smoke were significantly reduced; direct positive
      effects were strongly endorsed, and there was very low reporting of adverse
      effects. CONCLUSIONS: These findings demonstrate reliable blood nicotine delivery
      after the acute use of this brand/model of e-cigarette in a sample of regular
      users. Future studies might usefully quantify nicotine delivery in relation to
      inhalation technique and the relationship with successful smoking cessation/harm
      reduction.

PMID- 23978911
TI  - Targeting interleukin-22 in psoriasis.
AB  - Interleukin-22 (IL-22) is an IL-10 family cytokine that was recently discovered
      to be released by T helper 17 (Th17) cells, Th22 cells, etc. Recently, there is
      emerging evidence that IL-22 is involved in the development and pathogenesis of
      psoriasis. For instance, IL-22 can inhibit keratinocyte terminal differentiation
      and can induce psoriasis-like epidermis alterations; serum IL-22 levels were
      correlated with the disease severity of psoriasis patients, and IL-22 mRNA was
      positively expressed in the psoriatic skin lesions, but negatively expressed in
      the normal controls. All these findings suggest that IL-22 may be implicated in
      psoriasis; therapeutics targeting IL-22 may have promise as a potential
      therapeutic target for treating psoriasis. In the present review, we summarize
      recent advances on the role of IL-22 in the pathogenesis and treatment of
      psoriasis. 

PMID- 23978910
TI  - Biodegradable particles as vaccine antigen delivery systems for stimulating
      cellular immune responses.
AB  - There is a need for both new and improved vaccination formulations for a range of
      diseases for which current vaccines are either inadequate or non-existent.
      Biodegradable polymer-based vaccines fulfill many of the desired properties in
      achieving effective long-term protection in a manner that is safe, economical,
      and potentially more practicable on a global scale. Here we discuss some of the
      work performed with micro/nanoparticles made from either synthetic (poly[lactic
      co-glycolic acid] [PLGA] and polyanhydrides) or natural (chitosan) biodegradable
      polymers. Our attention is focused on, but not limited to, the generation of
      antitumor immunity where we stress the importance of particle size and co
      delivery of antigen and adjuvant. 

PMID- 23978912
TI  - High asymmetric dimethylarginine (ADMA) levels in patients with brucellosis.
AB  - Asymmetric dimethylarginine (ADMA) is the main endogenous inhibitor of nitric
      oxide synthase and is considered to be associated with endothelial dysfunction.
      Brucellosis, a zoonotic disease caused by Brucella spp., can manifest as
      vasculopathy. The present study was performed to investigate the relationship
      between ADMA and brucellosis. Serum samples from 39 patients with an accurate
      diagnosis of brucellosis and from 18 healthy control individuals were included in
      this study. ADMA levels were significantly higher in the patient group than the
      controls (P < 0.001). Receiver operating characteristic (ROC) curve analysis
      indicated that ADMA level >= 0.61 had a sensitivity of 79.5 %, specificity of
      88.9 %, positive predictive value of 93.9 %, and negative predictive value of
      66.7 %. This is the first report of an association between brucellosis and high
      levels of ADMA. In conclusion, ADMA levels should be tested in brucellosis cases
      and that further studies to clarify the mechanism underlying the association
      between ADMA and brucellosis are required.

PMID- 23978914
TI  - Meningococcal disease.
AB  - Meningococcal disease occurs as both endemic and epidemic disease in most parts
      of the world with significant morbidity and mortality. Among the different
      serogroups of Neisseria meningitidis, serogroups A, B, C account for 90% of the
      disease. In the last few years there has been a change in the epidemiology of the
      disease with an increase in the prevalence of serogroup C in Europe and North
      America, serogroup Y in the United States of America and Sweden, and W135 in the
      Kingdom of Saudi Arabia. The emergence of Neisseria meningitidis serogroup W135
      in the Kingdom of Saudi Arabia has lead to 2 major outbreaks mainly among
      Pilgrims during the Hajj season of 2000 and 2001. This has lead the health
      officials in the Kingdom of Saudi Arabia to change their vaccine requirements for
      the Umra and Hajj to include the quadrivalent meningococcal vaccine (A, C, Y,
      W135) instead of the bivalent one (A, C). Despite all the advances in prevention,
      diagnosis and treatment, the disease continues to have high mortality (5-10%).
      Prompt empirical treatment for suspected cases should include penicillin or a 3rd
      generation cephalosporin. A new conjugate vaccine against Neisseria meningitidis
      serogroup C has been recently licensed, while quadrivalent conjugate vaccine
      against serogroup A, C, Y and W135 is in early development. Meanwhile targeted
      vaccination with the available vaccines according to the epidemiology of the
      disease and rapid chemoprophylaxis for the close contacts of active cases are the
      most effective preventive strategies. 

PMID- 23978913
TI  - "Observation status" for hospitalized patients: implications of a proposed
      Medicare rules change.

PMID- 23978915
TI  - Autosomal dominant cerebellar ataxia type 1 in a Sudanese family.
AB  - OBJECTIVE: To study a large Sudanese family with a progressive autosomal dominant
      cerebellar ataxia and describe the clinical features and identify the genotype of
      the disorder. METHODS: This study was conducted during the year 1999 in the
      University Neurology Department of Shaab Teaching Hospital in Khartoum, Sudan.
      Affected individuals were identified by clinical examination or by reliable
      narrative data obtained from relatives of diseased or inaccessible family
      members. Routine laboratory blood and urine tests, cerebrospinal fluid analysis,
      cranial computerized tomography and nerve conduction studies were performed on
      the index patient and, if possible, family members. The genotype was identified
      by deoxyribonucleic acid analysis. RESULTS: Ten males and 12 females spanning 4
      generations were affected by autosomal dominant spinocerebellar ataxia. Genetic
      studies identified the mutation to be at the spinocerebellar ataxia 1 locus on
      chromosome p6. CONCLUSION: This is a report of a Sudanese family suffering from
      Type 1 autosomal dominant spinocerebellar ataxia.

PMID- 23978916
TI  - Diabetic neuropathy. Correlation with other diabetic microvascular complications.
AB  - OBJECTIVE: We studied the frequency of neuropathy in Saudi patients with definite
      diabetic microvascular complications and compared it to patients without
      complications. A high frequency of neuropathy in patients with definite
      microvascular complications would suggest a vascular etiology. METHODS: The study
      group consisted of 201 type-2 diabetic patients followed in the diabetic clinic
      of King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia. These
      patients were screened for microvascular disease. Only symmetrical distal sensory
      and motor neuropathy cases were included in the study. Screening for retinopathy
      was carried out according to Klien's criteria and nephropathy was diagnosed if
      albuminuria, microalbuminuria, abnormal blood urea nitrogen or creatinine was
      present. RESULTS: There was a strong correlation between the prevalence of
      diabetic peripheral neuropathy, retinopathy (P<0.001) and nephropathy (P<0.01),
      in patients with type 2 diabetes mellitus. This strong correlation suggests a
      common underlying pathogenesis. CONCLUSION: We conclude that microangiopathy may
      be a major factor in the pathogenesis of diabetic neuropathy. Major risk factors
      for microangiopathy are the degree of glycemic control and duration of diabetes.

PMID- 23978917
TI  - A profile of childhood neuropathies at a university hospital in Oman.
AB  - OBJECTIVE: To analyze all cases of childhood neuropathies (under 14 years of age)
      and report on their profile, pattern, clinical features and management. METHODS:
      Children with acute flaccid paralysis, longstanding weakness of extremities,
      neuroregression and children receiving anti cancer drugs with symptoms suggestive
      of neuropathy were evaluated for evidence of peripheral neuropathy. The
      evaluation of children with acute flaccid paralysis was a prospective study from
      January 1992 through to December 2000. The rest of the patients were studied
      retrospectively from the hospital medical records, pediatric neurology outpatient
      clinic and the neurophysiology laboratory, Sultan Qaboos University Hospital, Al
      Khod, Oman RESULTS: Eighty-two (39 Male: 43 Female) children were found to have
      peripheral neuropathy. Acute Guillain-Barre syndrome was the most common with 37
      children (45.1%), followed by genetic neuropathies [hereditary motor and sensory
      neuropathy with 17 (20.7%), hereditary sensory and autonomic neuropathy with 2
      (2.4%), hereditary spastic paraplegia associated neuropathy with 9 (11%) and
      metachromatic leucodystrophy with 9 (11%)]. Chronic inflammatory demyelinating
      neuropathy was seen in 5 (6.1%) and vincristine induced neuropathy in 3 (3.5%)
      children. CONCLUSION: Acute Guillain-Barre syndrome is the most common neuropathy
      amongst the acquired neuropathies. The treatable neuropathies constituted 54.7%
      (45 children) and the preventable genetic neuropathies accounted for the
      remaining 45.3% (37 children).

PMID- 23978918
TI  - Risk factors for drug-resistant Mycobacterium tuberculosis in Saudi Arabia.
AB  - OBJECTIVE: To identify rates of primary and secondary drug-resistant
      Mycobacterium tuberculosis and their risk factors from a tertiary-care center in
      the Kingdom of Saudi Arabia. METHODS: Review of microbiological and clinical data
      of all patients with positive isolates of Mycobacterium tuberculosis between 1995
      and 2000 at King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom
      of Saudi Arabia. RESULTS: Susceptibility to antituberculosis agents was tested in
      320 isolates from 320 patients. The median age was 50 years. Pulmonary
      tuberculosis was diagnosed in 106 (33%) patients, extrapulmonary in 183 (57%),
      and both in 31 (10%) patients. Two hundred forty-six isolates were sensitive to
      all 5 first line agents. Resistance to at least one of the first line agents was
      documented in 36 (11.3%) isolates. For the year 2000, resistance rates increased
      to 17.6%. Monoresistance was noted in 20 isolates (6.3%) and polyresistance in 16
      isolates (5.0%) including 9 multidrug-resistant Mycobacterium tuberculosis
      isolates (2.8%). Resistance rates for antituberculosis agents are: Isoniazid,
      9.1%; Rifampin, 2.8%; Ethambutol, 1.6%; Streptomycin, 5%; Pyrazinamide, 3.6%.
      Seventy-eight percent of the resistant isolates are considered primary
      resistance. History of antituberculosis therapy was the only risk factor
      associated with drug resistant Mycobacterium tuberculosis, odds ratio 19.9 (P<
      0.00001). The mean age of patients with resistant isolates was 42 years compared
      to 49 years in patients with susceptible isolates (P= 0.047). CONCLUSION: In a
      population of mostly Saudi patients, primary and secondary drug-resistant
      Mycobacterium tuberculosis is relatively low but has increased lately. Previous
      history of antituberculosis chemotherapy and young age are risk factors
      identified.

PMID- 23978919
TI  - Multiple sclerosis at Jordan University Hospital.
AB  - OBJECTIVE: A study of multiple sclerosis patients admitted to Jordan University
      Hospital over a 10-year-period with a comparison with other Western and Middle
      Eastern series. METHODS: The case notes of 32 patients with multiple sclerosis
      were reviewed to determine the age and sex distribution, clinical findings and
      results of investigations, treatment and outcome. RESULTS: There were 32 patients
      (24 females, 8 males, 3:1), with mean age at onset of 31.4 years, and range 6-50
      years. All patients fulfilled Poser's criteria for multiple sclerosis. The most
      common clinical manifestation was myelopathy followed by a polysymptomatic onset.
      Two-thirds of the patients had a relapsing - remitting course. The yield of
      cerebrospinal fluid oligoclonal banding was low (20%). The sensitivities of
      visual evoked potential was 62%, magnetic resonance imaging of brain 100%,
      magnetic resonance imaging of cervical spine was 70% and of dorsal spine 44%.
      Intravenous methylprednisolone Igr for 3-5 days was efficient in acute relapses
      for all patients. Beta-interferon was efficient in 2 out of 7 patients. After a
      mean follow-up of 5 years, two-thirds of the patients had mild to moderate
      disability (Extended disability status scale = 2 and 3). CONCLUSION: The age and
      sex distribution, clinical and magnetic resonance imaging findings were almost
      similar to other reports. However the yield of visual evoked potentials was low
      and that of cerebrospinal fluid oligoclonal banding was very low, the results of
      treatment with beta-interferon were modest and the outcome at a mean follow-up of
      5 years was relatively good.

PMID- 23978920
TI  - Hearing impairment in low birth weight children.
AB  - OBJECTIVE: To investigate the prevalence of hearing impairment in normal and low
      birth weight children. METHODS: A survey of 9540 Saudi children below 15 years of
      age was carried out. The survey was performed in the provinces of the Kingdom of
      Saudi Arabia from September 1994 to May 1998. The subjects were classified into
      low birth weight (up to 2.5 kg) and normal birth weight (>2.5 kg) groups. Each
      child was carefully examined for hearing status. RESULTS: The results of this
      study showed significantly high prevalence of hearing impairment in low birth
      weight children (14.87%) as compared to normal birth weight children (9.78%).
      CONCLUSION: Further studies are warranted to identify the potential risk factors
      associated with the high prevalence of hearing impairment in low birth weight
      children.

PMID- 23978921
TI  - Neural tube defects in newborns.
AB  - OBJECTIVE: The aim of this study was to review cases of neural tube defect with
      special focus on presentation, epidemiology and clinical presentation. Management
      with complications and results of surgery were discussed. METHODS: Ninety-three
      cases, born with neural tube defect (spina bifida aperta) were operated upon in
      our unit at King Hussein Medical Centre, Amman, Jordan, from June 1997 to October
      2000. Data was retrospectively reviewed and analyzed. RESULTS: Major neurological
      deficits were present in 28 cases (complete loss of function below the level of
      the lesion) and 19 cases were intact. Lesion size was less than 3.5 cm in 72
      cases (77.4%); 3.5-7.5 cm in 15 cases (16.1%) and 6 cases were more than 7.5 cm.
      Seventy-two cases had an intact lesion before surgery while the other 21 cases
      ruptured either during delivery or soon later. For the site of lesion, 51 cases
      were lumbar, 22 cases were lumbosacral, 13 cases were thoracolumbar, 4 cases were
      thoracic and 3 cases were cervical. Early surgery was carried out for all cases,
      primary closure was possible in all cases. Nineteen cases had post-operative
      complications, wound infection (superficial) 6 cases (7%), leakage of
      cerebrospinal fluid 5 cases (5%), meningitis 3 cases (3%), skin necrosis 3 cases
      (3%) and 2 deaths. CONCLUSION: Jordan has a large number of born spina bifida
      cases, as the practice of pregnancy termination is socially and religiously
      unacceptable. Our approach to management, is to repair all intact patients. For
      patients with major neurological deficits we advise the family on the natural
      history of the disease and postoperative status of the patient leaving the
      decision to the family. The presentation was similar to that described in
      literature.

PMID- 23978922
TI  - Socio-demographic study of major depression in Qatar.
AB  - OBJECTIVE: To evaluate the socio-demographic characteristics of major depressive
      disorders in the State of Qatar, which has a high percentage of expatriates.
      METHODS: Out of 7460 outpatient psychiatric clinic attendees at Hamad Medical
      Corporation, Doha, Qatar, between November 1993 through December 1998, 2483
      patients met the diagnosis of depressive disorder. Prospectively, we interviewed
      1114 patients who met the diagnosis of Depressive Episode and Recurrent
      Depressive Disorder according to International Classification of Disease-10
      (major depressive disorder according to Diagnostic and Statistical Manual-IV).
      The data was coded and analyzed by using Statistical Package for Social Sciences
      under windows. RESULTS: Thirty-three point three percent of the patients met the
      diagnosis of depressive disorder and those with major depressive disorder were
      14.9% of the total. Of those with major depressive disorder approximately 2/3rd
      had a single depressive episode and one 3rd had recurrent attacks. Major
      depressive disorder is significantly equal in both sexes, married patients of
      both sexes have a significantly higher rate than others. There is a remarkable
      consistent rise in the frequency of recurrent depression, compared with
      significant decline in frequency of single depression with age. Major depressive
      disorder is significantly more among the unemployed. Among the employed, skilled
      workers have significantly higher rate of major depressive disorder than non
      skilled and professionals. CONCLUSION: In nonhomogeneous societies such as Qatar
      and the Arabian Gulf in general, where men outnumber women, the distribution of
      major depressive disorder among outpatients is inconsistent with other studies.
      Age, sex and occupation are the important risk factors for major depressive
      disorder. Marriage has no protective effect in major depressive disorder.

PMID- 23978923
TI  - Neuromyelitis optica.
AB  - Neuromyelitis optica disease is characterized by simultaneous or successive
      attacks involving both the optics nerves and spinal cord without any evidence of
      the disease elsewhere. We report a 22-year-old Saudi woman with relapsing
      neuromyelitis optica disease. She had all the clinical, cerebrospinal fluid, and
      radiological features that differ from primary demyelinating disease. However,
      our patient responded well to long-term corticosteroid therapy and azathioprine
      with improvement in her expanded disability status scale, and ambulation. In
      addition, no acute relapses occurred with significant improvement on magnetic
      resonance imaging lesions and favorable outcome. 

PMID- 23978924
TI  - Pathoanatomical correlation of bladder sparing in cauda equina syndrome due to
      posteriorly sequestered lumbar disc herniation.
AB  - The pathoanatomical explanation of lumbar disc herniation causing the rare cauda
      equina syndrome with sacral 2- sacral 4 roots sparing is not well described. A
      case report of bladder sparing cauda equina syndrome due to a large posteriorly
      sequestered lumbar disc fragment is presented. Magnetic resonance imaging of the
      lumbosacral spine showed herniation of a large disc fragment at lumbar 3-lumbar 4
      deforming the thecal sac posteriorly, with the left side more affected than the
      right. Bladder sparing cauda equina syndrome can be explained by the anatomical
      organization of the nerve roots within the thecal sac. The medial sacral roots
      are not as stretched and strained by the herniating disc as the laterally placed
      lumbar roots. Early laminectomy and decompression of the thecal sac may relieve
      this stretch and strain on the nerve roots and therefore preserve bladder
      function. 

PMID- 23978925
TI  - Cerebellar abscess due to Listeria monocytogenes.
AB  - Brain abscess due to listeria monocytogenes mainly involves the cerebral
      hemispheres. Cerebellar abscess is an infrequent event, which could lead to rapid
      neurological deterioration if unrecognized. We present a case of multiple brain
      stem and cerebellar abscesses in a previously healthy individual exposed to
      unpasteurized milk. This is the 2nd case of cerebellar abscess due to listeria
      monocytogenes reported in the English literature. The diagnosis of listeria
      monocytogenes was made in the surgical specimen. Our case illustrates the
      difficulty of early diagnosis of cerebellar listeria monocytogenes abscesses and
      the importance of prompt neurosurgical intervention. 

PMID- 23978926
TI  - Difficulties in diagnosing neuroleptic malignant syndrome.
AB  - This report describes a recent case of neuroleptic malignant syndrome, a rare
      adverse effect of antipsychotic medications. Assessment of the neuroleptic
      malignant syndrome was carried out by using the Naranjo Algorithm Probability
      Scale which resulted in a highly probable reaction to haloperidol. The
      difficulties in establishing the diagnosis in this patient lead to late
      intervention resulting in a slow recovery and prolonged hospitalization. Our
      objective in this presentation is to highlight the importance of early
      recognition of this potentially fatal adverse drug reaction. 

PMID- 23978927
TI  - Multiple sclerosis simulating brain tumor.
AB  - We report a case of a 29-year-old female patient with atypical magnetic resonance
      image appearance of multiple sclerosis simulating brain tumor on magnetic
      resonance images, that proved to be a demyelinating disease on brain biopsy.
      Steroid pulse therapy produced regression of the lesions on magnetic resonance
      images. 

PMID- 23978928
TI  - Infundibular buckling as an adjunctive sign of Pituitary adenoma.

PMID- 23978929
TI  - Drug resistant Mycobacterium tuberculosis in Saudi Arabia.

PMID- 23978930
TI  - The face inversion effect in non-human primates revisited - an investigation in
      chimpanzees (Pan troglodytes).
AB  - Faces presented upside-down are harder to recognize than presented right-side up,
      an effect known as the face inversion effect. With inversion the perceptual
      processing of the spatial relationship among facial parts is disrupted. Previous
      literature indicates a face inversion effect in chimpanzees toward familiar and
      conspecific faces. Although these results are not inconsistent with findings from
      humans they have some controversy in their methodology. Here, we employed a
      delayed matching-to-sample task to test captive chimpanzees on discriminating
      chimpanzee and human faces. Their performances were deteriorated by inversion.
      More importantly, the discrimination deterioration was systematically different
      between the two age groups of chimpanzee participants, i.e. young chimpanzees
      showed a stronger inversion effect for chimpanzee than for human faces, while old
      chimpanzees showed a stronger inversion effect for human than for chimpanzee
      faces. We conclude that the face inversion effect in chimpanzees is modulated by
      the level of expertise of face processing. 

PMID- 23978931
TI  - Plasmodium vivax malaria vaccines: why are we where we are?
AB  - Malaria is one of the few diseases in which morbidity is still measured in
      hundreds of millions of cases every year. Plasmodium vivax and Plasmodium
      falciparum are responsible for nearly all the malaria cases in the world and
      despite difficulties in obtaining an exact number, estimates indicate an
      astonishing 349-552 million clinical cases of malaria due to P. falciparum in
      2007 and between 132-391 million clinical episodes due to P. vivax in 2009. It is
      becoming evident that eradication of malaria will be an arduous task and P. vivax
      will be one of the most difficult species to eliminate and perhaps become the
      last standing malaria parasite. Indeed, in countries that succeed in decreasing
      the disease burden, nearly all the remaining malaria cases are caused by P.
      vivax. Such resilience is mainly due to the sophisticated mechanism that the
      parasite has evolved to remain dormant for months or years forming hypnozoites, a
      small structure in the liver that will be a major hurdle in the efforts toward
      malaria eradication. Furthermore, while clinical trials of vaccines against P.
      falciparum are making fast progress, a very different picture is seen with P.
      vivax, where only few candidates are currently active in clinical trials. 

PMID- 23978932
TI  - A zero-strain layered metal oxide as the negative electrode for long-life sodium
      ion batteries.
AB  - Room-temperature sodium-ion batteries have shown great promise in large-scale
      energy storage applications for renewable energy and smart grid because of the
      abundant sodium resources and low cost. Although many interesting positive
      electrode materials with acceptable performance have been proposed, suitable
      negative electrode materials have not been identified and their development is
      quite challenging. Here we introduce a layered material, P2
      Na0.66[Li0.22Ti0.78]O2, as the negative electrode, which exhibits only ~0.77%
      volume change during sodium insertion/extraction. The zero-strain characteristics
      ensure a potentially long cycle life. The electrode material also exhibits an
      average storage voltage of 0.75 V, a practical usable capacity of ca. 100 mAh g(
      1), and an apparent Na(+) diffusion coefficient of 1 * 10(-10) cm(-2) s(-1) as
      well as the best cyclability for a negative electrode material in a half-cell
      reported to date. This contribution demonstrates that P2-Na0.66[Li0.22Ti0.78]O2
      is a promising negative electrode material for the development of rechargeable
      long-life sodium-ion batteries. 

PMID- 23978933
TI  - Non-invasive NMR stratigraphy of a multi-layered artefact: an ancient detached
      mural painting.
AB  - NMR stratigraphy was used to investigate in situ, non-destructively and non
      invasively, the stratigraphy of hydrogen-rich layers of an ancient Nubian
      detached mural painting. Because of the detachment procedure, a complex multi
      layered artefact was obtained, where, besides layers of the original mural
      painting, also the materials used during the procedure all became constitutive
      parts of the artefact. NMR measurements in situ enabled monitoring of the state
      of conservation of the artefact and planning of minimum representative sampling
      to validate results obtained in situ by solid-state NMR analysis of the samples.
      This analysis enabled chemical characterization of all organic materials. Use of
      reference compounds and prepared specimens assisted data interpretation. 

PMID- 23978934
TI  - Solid-phase extraction based on hydrophilic interaction liquid chromatography
      with acetone as eluent for eliminating matrix effects in the analysis of
      biological fluids by LC-MS.
AB  - Analysis of drugs and metabolites in biological matrices such as blood or plasma
      by LC-MS is routinely challenged by the presence of large quantities of competing
      molecules for ionization in soft ionization sources, such as proteins and
      phospholipids. While the former can easily be removed by protein precipitation,
      pre-analytical extraction of the latter is necessary because they show very high
      retention in reversed-phase LC resulting in long analysis times or in ion
      suppression effects when not eluted before the next runs. A novel HILIC-based SPE
      approach, making use of silica cartridges and of acetone as organic solvent, is
      introduced as a potent alternative to current commercial methods for phospholipid
      removal. The methodology was developed and tested for a broad polarity range of
      pharmaceutical solutes (log P from 0 to 6.6) and broad applicability can
      therefore be envisaged. 

PMID- 23978936
TI  - Development of the performance reference compound approach for the calibration of
      "polar organic chemical integrative sampler" (POCIS).
AB  - The purpose of the Water Framework Directive is to ensure the quality of the
      natural water across Europe. In this context, passive samplers have shown
      interesting capacities for the monitoring of contaminants in aqueous ecosystems.
      They allow the measurement of time-weighted average concentrations, overcoming
      many drawbacks of the spot-sampling techniques known to be expensive and time
      consuming. However, application of passive samplers such as polar organic
      chemical integrative samplers (POCIS) for the monitoring of hydrophilic
      contaminants requires calibration to define compound sampling rates; key
      parameters to deduce the pollutant water concentrations from the amounts of
      pollutants accumulated by the device. Unfortunately, sampling rates are
      influenced by a range of environmental factors; in that respect, a question
      remains: is it not evident to know to what extent the sampling rates obtained in
      laboratory experiments can be used in field conditions? The problem can be solved
      for hydrophobic samplers by using performance reference compounds (PRCs), and an
      ongoing challenge for POCIS is focused on the improvement of the quantitative
      aspect of this family of samplers. In this study, potential PRCs have been
      selected during a specific experiment and their performance was tested in the
      laboratory under two hydrodynamic conditions. Results revealed a good
      proportionality between elimination rates of PRCs and sampling rates of
      chemicals. Afterwards, the application of the approach under environmental
      conditions was assessed by deploying POCIS in the Arcachon Bay (France) where
      POCIS-PRC-derived water concentrations appear to be close to the simultaneous
      grab-sampling results. 

PMID- 23978937
TI  - Optimization of global DNA methylation measurement by LC-MS/MS and its
      application in lung cancer patients.
AB  - Global analyses of DNA methylation contribute important insights into biology and
      the wide-ranging role of DNA methylation. We describe the use of online solid
      phase extraction and isotope-dilution liquid chromatography/tandem mass
      spectrometry (LC-MS/MS) for the simultaneous measurement of 5-methyl-2'
      deoxycytidine (5-medC) and 2'-deoxycytidine (dC) in DNA. With the incorporation
      of isotope internal standards and online enrichment techniques, the detection
      limit of this method was estimated to be as low as 0.065 pg which enables human
      global DNA methylation detection using only picogram amounts of DNA. This method
      was applied to assess the optimal amounts of enzymes required for DNA digestion
      regarding an accurate global DNA methylation determination and completeness of
      digestion and to determine global methylation in human tumor adjacent lung tissue
      of 79 lung cancer patients. We further determined methylated (N7-methylguanine
      (N7-meG), O (6)-methylguanine (O (6)-meG), and N3-methyladenine (N3-meA)) and
      oxidized DNA lesions (8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)) in lung
      cancer patients by LC-MS/MS. Optimization experiments revealed that dC was
      liberated from DNA much more readily than 5-medC by nuclease P1 and alkaline
      phosphatase (AP) in DNA, which could lead to an error in the global DNA
      methylation measurement following digestion with insufficient enzymes. Nuclease
      P1 showed more differential activity for 5-medC and dC than AP. Global DNA
      methylation levels in adenocarcinoma and squamous cell carcinoma patients were
      similar in the range of 3.16-4.01 %. Global DNA methylation levels were not
      affected by smoking and gender and were not correlated with N7-meG or 8-oxodG in
      lung cancer patients. Levels of O (6)-meG and N3-meA were however found to be
      undetectable in all lung tissue samples.

PMID- 23978938
TI  - Innovative technique for the direct determination of proteins in calcified aortic
      valves.
AB  - Aortal valve mineralization very frequently causes a genesis of aortic stenosis,
      which is the most often surgically treated heart disease. Hydroxyapatite deposits
      have been identified as one of the causes leading to the loss of elasticity of
      the aortic valves. It is known that phosphates/calcium is accumulated in valve
      tissues during mineralization, but the mechanism of this process remains unclear.
      The work is focused mainly on the study of protein composition of mineralized
      aortic valves by nano-liquid chromatography electrospray ionization in a
      quadrupole orthogonal acceleration time-of-flight mass spectrometry. New
      methodological approach based on direct enzymatic digestion of proteins contained
      in hydroxyapatite deposits was developed for the study of pathological processes
      connected with osteogenesis. Our objectives were to simplify the traditional
      analytical protocols of sample preparation and to analyze the organic components
      of the explanted aortic valves for significant degenerative aortic stenosis. The
      study of aortic valve mineralization on the molecular level should contribute to
      understanding this process, which should consequently lead to effective
      prevention as well as to new ways of treatment of this grave disease. 

PMID- 23978939
TI  - Effect of port-care frequency on venous port catheter-related complications in
      cancer patients.
AB  - PURPOSE: Subcutaneous central venous port catheters (SCVPC) are of great
      importance in the treatment of patients with malignancies since they provide
      secure vascular access. Our aim was to assess the impact of long-term catheter
      care frequency on the frequency of port-related complications. PATIENTS AND
      METHODS: Two hundred and seven patients who had not been on active chemotherapy
      through their SCVPC for at least 3 months were enrolled into the study. Those who
      received catheter care every 3 months or more frequently were assigned to the
      frequent care group, and the others to the infrequent care group. The patients
      were examined for port-related complications and thrombosis including port
      occlusion. Routinely in our clinic, catheter care was done by using 300 IU of
      heparin. RESULTS: According to the frequency of SCVPC care, 49 (23.7 %) patients
      were in the frequent care group and 158 (76.3 %) were in the infrequent care
      group. Median follow-up of all patients was 671 days (range 133-1712). Median
      frequency of port care in the frequent care group was 90 days (range 30-90), but
      441.5 days in the infrequent care group (range 91-1630). None of the patients
      experienced port-related severe complications during the follow-up time. None of
      them presented with port occlusion. When the groups were analysed for thrombus
      (symptomatic and asymptomatic), there was no statistically significant difference
      (6.4 vs 13.8 %, p = 0.17). Those patients who had received more than first-line
      chemotherapy were found to have more thrombi than the patients who were treated
      with only one type of chemotherapy protocol (28.6 vs 10.2 %, p = 0.01), and the
      patients who had metastatic disease at the last control were found out to have
      thrombi more frequently than the non-metastatic patients (24.3 vs 9.3 %) (p =
      0.01). CONCLUSIONS: In the present study, there was no difference in port-related
      severe complications between frequent and infrequent care groups during follow
      up. However, the rate of thrombosis was slightly higher in the infrequent port
      care group.

PMID- 23978940
TI  - Light transmission of the ocular media in birds and mammals.
AB  - Differences in the ultraviolet (UV) cutoff of ocular media between birds and
      mammals have been revealed by spectrophotometric measurements of the transmission
      of light wavelengths by the cornea, lens and vitreous body in chickens, crows,
      quails, rats, rabbits and pigs. The light transmission values of the cornea were
      shown to be above 50% for wavelengths of 330-800 nm in birds, 300-800 nm in rat
      and 310-800 nm in mammals except for rat. For the lens, the light transmission
      values were shown to be above 50% for wavelengths of 320-800 nm in birds and rat
      and 390-800 nm in mammals except for rat. Thus, among the ocular media, the
      cornea in birds and the lens in mammals except for rat may play a role as a major
      UV cutoff filter. 

PMID- 23978941
TI  - Molecular demonstration of hemotropic mycoplasmas in wild Japanese monkeys
      (Macaca fuscata).
AB  - The prevalence of hemotropic mycoplasmas in wild monkeys is largely unknown.
      Here, we report the presence of hemoplasmas in blood specimens collected from
      wild Japanese monkeys (Macaca fuscata) tentatively captured for ecological survey
      in Mie prefecture, Japan. We examined 9 monkeys using hemoplasma-specific real
      time PCR and found all of them positive for a hemoplasma infection. The 16S rRNA
      gene and 16S to 23S rRNA intergenic spacer region of the hemoplasma detected in
      wild monkeys were amplified using end-point PCR. The nucleotide sequences of the
      PCR products were further determined and compared to those of other hemoplasmas.
      Our examinations revealed a wide prevalence of a hemoplasma strain in Japanese
      monkeys, which was similar to 'Candidatus Mycoplasma haemomacaque' reported in
      cynomolgus monkeys (Macaca fascicularis). Pathogenic traits of this hemoplasma
      strain remain unexplored. 

PMID- 23978942
TI  - [Extensive left ventricular myocardial fat deposition detected by cardiac MRI].
AB  - Although it is well known from pathological studies that intramyocardial fat
      deposition frequently occurs after left ventricular myocardial infarction, a left
      ventricular fat deposition is rarely diagnosed in the clinical routine. We report
      the case of extensive fat deposition in the left ventricular myocardium which was
      detected by routine cardiac magnetic resonance imaging. 

PMID- 23978943
TI  - Acquired neuromyotonia heralding recurrent thymoma in myasthenia gravis.
AB  - IMPORTANCE: Acquired neuromyotonia is increasingly recognized as an autoimmune
      disorder, frequently associated with antibodies against voltage-gated potassium
      channel complex proteins.We present a case of acquired neuromyotonia as the
      heralding symptom of recurrent thymoma in a patient with myasthenia gravis.
      OBSERVATIONS: A report of a single case of a 53-year-old man with myasthenia
      gravis and a prior thymectomy presenting with 2 months of diffuse, involuntary
      muscle twitching in the absence of myasthenic symptoms, electrophysiologically
      confirmed to be neuromyotonia. Further evaluation revealed the recurrence of
      malignant thymoma, accompanied by refractory arrhythmia. Serologic and
      cerebrospinal fluid testing confirmed the presence of antibodies directed against
      2 voltage-gated potassium channel-associated proteins: LGI1 and Caspr2.
      CONCLUSIONS AND RELEVANCE: This case highlights the overlap of myasthenia,
      neuromyotonia, and thymoma, emphasizing the importance of appropriate tumor
      screening in the presence of either of the former 2 conditions.

PMID- 23978944
TI  - Long-term results of a prospective randomized trial evaluating G-CSF priming in
      intensive induction chemotherapy followed by autologous stem cell transplantation
      in elderly patients with acute myeloid leukemia.
AB  - Few studies have evaluated granulocyte colony-stimulating factor (G-CSF) priming
      in elderly patients with intensively treated acute myeloid leukemia (AML), and no
      data are available for genetically defined AML subgroups. We provide long-term
      results (median follow-up 7.6 years) of a randomized trial in which 183 patients
      (median age 67 years) received G-CSF prior to (G-CSF priming) or after two cycles
      of induction chemotherapy. CR rates with G-CSF priming and G-CSF post
      chemotherapy were comparable (57 vs. 67 %, p = 0.153), with overall survival (OS)
      probabilities of 14 vs. 17 % at 10 years. Induction mortality was significantly
      higher with G-CSF priming (23 vs. 10 %, p = 0.015), primarily in normal karyotype
      (NK) AML. In this subgroup, a trend for better relapse-free survival (RFS) was
      observed with G-CSF priming (44 vs. 22 % at 10 years, p = 0.074) but did not
      translate into an OS benefit. G-CSF priming had no impact on AML with FLT3-ITD
      and NPM mutations and did not improve outcome in patients with adverse
      cytogenetics. In a landmark analysis, late consolidation with autologous stem
      cell transplantation or a second consolidation cycle significantly improved RFS
      compared with one consolidation cycle (21.0 vs. 12.8 months, p = 0.046). Future
      studies on G-CSF priming should be restricted to NK AML and used only in post
      remission therapy. 

PMID- 23978946
TI  - Overexpressed BAG3 is a potential therapeutic target in chronic lymphocytic
      leukemia.
AB  - Bcl-2-associated athanogene 3 (BAG3), a member of BAG family, is shown to sustain
      cell survival and underlie resistance to chemotherapy in human neoplastic cells.
      We aimed to determine the exact role and underlying mechanisms of BAG3 in human
      chronic lymphocytic leukemia (CLL). One hundred human CLL samples and 20 normal B
      cell samples from healthy controls were collected. We measured the BAG3
      expression in these cells and explored its relationship with known prognostic
      factors for CLL. The roles of BAG3 in cell apoptosis and migration were evaluated
      by small interfering RNA-mediated knockdown of BAG3 in primary CLL cells. We
      showed that BAG3 expression level was increased in CLL cells compared with normal
      B cells. Moreover, BAG3 expression was particularly upregulated in CD38 positive,
      unmutated immunoglobulin heavy-chain patients and those with lymphadenopathy
      and/or splenomegaly. Importantly, patients with increased BAG3 expression level
      have poor overall survival in subgroups with positive ZAP-70 or those without any
      "p53 abnormality". In addition, knocking down of BAG3 expression resulted in
      increased apoptotic ratio and decreased migration in primary CLL cells. Our data
      indicate that BAG3 is a marker of poor prognostic in specific subgroups of CLL
      patients and may be a potential therapeutic target for this disease. 

PMID- 23978945
TI  - CHO(E)P-14 followed by alemtuzumab consolidation in untreated peripheral T cell
      lymphomas: final analysis of a prospective phase II trial.
AB  - The rate of long-term remissions after treatment of peripheral T cell lymphomas
      (PTCL) with standard CHOP-like protocols is unsatisfactory. A prospective
      multicenter phase II trial was initiated in untreated patients with PTCL of all
      International Prognostic Index-risk groups, evaluating alemtuzumab consolidation
      in patients with complete or good partial remission after CHO(E)P-14 induction.
      Twenty-nine (70.7 %) of the 41 enrolled patients received alemtuzumab
      consolidation (133 mg in total). The main grades 3-4 toxicities during
      alemtuzumab therapy were infections and neutropenia with one potentially
      treatment-related death. Complete responses were seen in 58.5 %, partial
      responses in 2.4 % and 29.3 % had progressive disease. After a median observation
      time of 46 months, 19 patients have died, 16 of them due to lymphoma and/or
      salvage therapy complications. Event-free and overall survival at 3 years in the
      whole intent to treat population are 32.3 and 62.5 %, respectively, and 42.4 and
      75.1 % in the patients who received alemtuzumab. In conclusion, application of a
      short course of alemtuzumab after CHO(E)P-14 induction is feasible although
      complicated by severe infections. A current phase III trial, applying alemtuzumab
      as part of the initial chemotherapy protocol to avoid early progression, will
      further clarify its significance for the therapeutic outcome. 

PMID- 23978947
TI  - Ultrasound-guided sciatic nerve pulsed radiofrequency for chronic knee pain
      treatment: a novel approach.
AB  - Chronic knee pain management with current nonpharmacological or pharmacological
      measures often has suboptimal results and significant side effects. Sciatic nerve
      pulsed radiofrequency (SNPRF) is an unexplored alternative for chronic knee pain
      management. We show a prospective short series of chronic knee pain patients
      managed with ultrasound-guided SNPRF. Visual analogue scale (VAS) was measured at
      baseline and 4 weeks after the procedure. The study included 25 elderly patients
      with severe knee pain. A total of 47 procedures were performed during a 3-month
      period. VAS scores showed a significant pain difference (p < 0.001) in successive
      comparison. No patient reported adverse events during the 1-month follow-up
      period. Ultrasound-guided SNPRF is a new approach for chronic knee pain
      management that leads to significant pain reduction in the short term. Randomized
      studies with adequate size, longer follow-up period, and appropriate evaluating
      tools are warranted to verify these preliminary data.

PMID- 23978949
TI  - A novel aptamer-based competition strategy for ultrasensitive electrochemical
      detection of leukemia cells.
AB  - A robust, nanobiotechnology-based electrochemical cytosensing platform for the
      detection of acute leukemia cells was developed with high sensitivity,
      selectivity, acceptable rapidity and excellent extensibility. It utilized the
      competitive binding of cell-specific aptamers to acute leukemia cells and
      subsequent voltammetric quantification of the metal signature. Greatly enhanced
      sensitivity was achieved with dual signal amplification by using Fe3O4 magnetic
      nanoparticles (MNPs) as carriers to load a large amount of gold nanoparticles
      (AuNPs) and AuNP-catalyzed silver deposition. The proposed competitive cytosensor
      showed high sensitivity with a detection limit down to 10 cells. This simple and
      low-cost electrochemical cytosensing approach offers great promise to extend its
      application to early detection of human leukemia and possibly to other cancer
      cells. 

PMID- 23978948
TI  - Knee strength retention and analgesia with continuous perineural fentanyl
      infusion after total knee replacement: randomized controlled trial.
AB  - PURPOSE: Despite providing adequate pain relief, a femoral nerve block can induce
      postoperative muscle weakness after total knee arthoplasty (TKA). Fentanyl has
      been shown to have peripheral effects but has not been used as a perineural
      infusate alone after TKA. METHODS: Sixty patients scheduled for TKA were
      randomized to one of three blinded groups: a continuous 24 h infusion of either
      fentanyl 3 MUg/ml, ropivacaine 0.1%, or 0.9% normal saline through a femoral
      nerve sheath catheter at 10 ml/h. The main outcome was maximum voluntary
      isometric contraction (MVIC) in the quadriceps femoris (knee extension), measured
      by a handheld dynamometer (Nm/kg). Other variables assessed were preoperative and
      postoperative visual analog scale (VAS) scores, hamstrings MVIC (knee flexion),
      active range of motion of the operative knee, distance ambulated, incidence of
      knee buckling, supplemental morphine usage, postoperative side effects, and serum
      fentanyl levels. RESULTS: Quadriceps MVIC values were significantly greater in
      the fentanyl group compared to the group that received ropivacaine (median
      values, 0.08 vs. 0.03 Nm/kg; p = 0.028). The incidence of postoperative knee
      buckling upon ambulation was higher in the ropivacaine group compared to the
      fentanyl group, although not statistically significant (40% vs. 15 %,
      respectively; p = 0.077). VAS scores while ambulating were not significantly
      different between the fentanyl group and the ropivacaine group (p = 0.270).
      Postoperative morphine consumption, nausea and vomiting, and resting VAS scores
      were similar among the three groups. CONCLUSIONS: A continuous perineural
      infusion of fentanyl produced greater strength retention than ropivacaine post
      TKA.

PMID- 23978950
TI  - Risk of thyroid cancer based on thyroid ultrasound imaging characteristics:
      results of a population-based study.
AB  - IMPORTANCE: There is wide variation in the management of thyroid nodules
      identified on ultrasound imaging. OBJECTIVE: To quantify the risk of thyroid
      cancer associated with thyroid nodules based on ultrasound imaging
      characteristics. METHODS: Retrospective case-control study of patients who
      underwent thyroid ultrasound imaging from January 1, 2000, through March 30,
      2005. Thyroid cancers were identified through linkage with the California Cancer
      Registry. RESULTS: A total of 8806 patients underwent 11,618 thyroid ultrasound
      examinations during the study period, including 105 subsequently diagnosed as
      having thyroid cancer. Thyroid nodules were common in patients diagnosed as
      having cancer (96.9%) and patients not diagnosed as having thyroid cancer
      (56.4%). Three ultrasound nodule characteristics--microcalcifications (odds ratio
      [OR], 8.1; 95% CI, 3.8-17.3), size greater than 2 cm (OR, 3.6; 95% CI, 1.7-7.6),
      and an entirely solid composition (OR, 4.0; 95% CI, 1.7-9.2)--were the only
      findings associated with the risk of thyroid cancer. If 1 characteristic is used
      as an indication for biopsy, most cases of thyroid cancer would be detected
      (sensitivity, 0.88; 95% CI, 0.80-0.94), with a high false-positive rate (0.44;
      95% CI, 0.43-0.45) and a low positive likelihood ratio (2.0; 95% CI, 1.8-2.2),
      and 56 biopsies will be performed per cancer diagnosed. If 2 characteristics were
      required for biopsy, the sensitivity and false-positive rates would be lower
      (sensitivity, 0.52; 95% CI, 0.42-0.62; false-positive rate, 0.07; 95% CI, 0.07
      0.08), the positive likelihood ratio would be higher (7.1; 95% CI, 6.2-8.2), and
      only 16 biopsies will be performed per cancer diagnosed. Compared with performing
      biopsy of all thyroid nodules larger than 5 mm, adoption of this more stringent
      rule requiring 2 abnormal nodule characteristics to prompt biopsy would reduce
      unnecessary biopsies by 90% while maintaining a low risk of cancer (5 per 1000
      patients for whom biopsy is deferred). CONCLUSIONS AND RELEVANCE: Thyroid
      ultrasound imaging could be used to identify patients who have a low risk of
      cancer for whom biopsy could be deferred. On the basis of these results, these
      findings should be validated in a large prospective cohort.

PMID- 23978951
TI  - Generation of more effective cancer vaccines.
AB  - Cancer vaccines represent a promising therapeutic approach for which prime time
      is imminent. However, clinical efficacy must be improved in order for cancer
      vaccines to become a valid alternative or complement to traditional cancer
      treatments. Considerable efforts have been undertaken so far to better understand
      the fundamental requirements for clinically-effective cancer vaccines. Recent
      data emphasize that important requirements, among others, are (1) the use of
      multi-epitope immunogens, possibly deriving from different tumor antigens; (2)
      the selection of effective adjuvants; (3) the association of cancer vaccines with
      agents able to counteract the regulatory milieu present in the tumor
      microenvironment; and (4) the need to choose the definitive formulation and
      regimen of a vaccine after accurate preliminary tests comparing different antigen
      formulations. The first requirement deals with issues related to HLA restriction
      of tumor antigen presentation, as well as usefulness of tumor antigen spreading
      and counteraction of immune escape phenomena, linked to tumor antigen down
      modulation, for an effective anti-cancer immune response. The second point
      underscores the necessity of optimal activation of innate immunity to achieve an
      efficient adaptive anti-cancer immune response. The third point focuses on the
      importance to inhibit subsets of regulatory cells. The last requirement stresses
      the concept that the regimen and formulation of the vaccine impacts profoundly on
      cancer vaccine efficacy. A new generation of cancer vaccines, provided with both
      immunological and clinical efficacy, will hopefully soon address these
      requirements. 

PMID- 23978952
TI  - Effects of intranasal steroid treatment on the presence of biofilms in non
      allergic patients with chronic rhinosinusitis with nasal polyposis.
AB  - Microbial biofilms have been implicated in the pathogenesis of chronic
      rhinosinusitis with nasal polyposis (CRSwNP). Intranasal application of
      corticosteroids (INCS) is a reliable option in the management of CRSwNP. INCS
      medication has been suspected to influence the presence and thickness of
      microbial biofilms and inflammatory cell patterns in CRSwNP. Two series of
      identical nasal polyps obtained from non-allergic patients with CRSwNP (n = 56),
      who underwent endoscopic sinus surgery (ESS), were processed to hematoxylin-eosin
      (H.E.) and Gram staining, respectively. Patients were recruited into three
      groups. Group A (n = 21) consisted of patients with continuous preoperative INCS
      treatment. In group B (n = 17), patients were never treated by INCS, while in
      group C (n = 18) INCS medication was stopped at least 6 months before ESS.
      Biofilm positivity varied from 76.4 to 88.8% in different subject groups. These
      values and average thickness of biofilms did not reach statistically significant
      levels (Mann-Whitney's U probe, p > 0.05) in different patient groups. In
      contrast, microscopic pattern and numbers of predominant inflammatory cell
      populations displayed obvious differences according to INCS treatment (Mann
      Whitney's U probe, p < 0.001). According to these observations, INCS treatment
      does not affect the presence and thickness of microbial biofilms in CRSwNP. In
      contrast, it has significant effects on the pattern of inflammatory cells
      infiltrating the subepithelial layer, which might result in beneficially altered
      extracellular matrix production and cytokine release.

PMID- 23978954
TI  - Cancer risk in inflammatory bowel disease according to patient phenotype and
      treatment: a Danish population-based cohort study.
AB  - OBJECTIVES: Population-based studies of site-specific cancer risk in patients
      with inflammatory bowel disease (IBD) according to IBD phenotype and treatment
      are lacking. We studied cancer risk in a well-characterized population-based IBD
      cohort from North Jutland County, Denmark. METHODS: A total of 1,515 patients
      were diagnosed with ulcerative colitis (UC) and 810 with Crohn's disease (CD)
      during 1978-2002. Patients were followed until 31 December 2010 for occurrence of
      incident cancer, identified in the Danish Cancer Registry. Observed numbers of
      cancer were compared with expected numbers (based on age- and sex-specific
      background rates) and presented as standardized incidence ratios (SIRs) with 95%
      confidence intervals (CIs). RESULTS: Patients with UC were not at increased risk
      of cancer overall (SIR, 1.12; 95% CI, 0.97-1.28) despite increased risk of
      prostate cancer (SIR, 1.82; 95% CI, 1.17-2.71). Patients with CD had a 55%
      increased risk of cancer overall (SIR, 1.55; 95% CI, 1.29-1.84) related to young
      age, colonic disease, smoking, and thiopurine exposure. Patients were at
      increased risk of small bowel cancer (SIR, 15.18; 95% CI, 1.84-54.78), lung
      cancer (SIR, 2.13; 95% CI, 1.19-3.52 (associated with female gender and
      smoking)), colorectal cancer in males (SIR, 2.43; 95% CI, 1.05-4.78), cervical
      dysplasia (SIR, 1.65; 95% CI, 1.10-2.37 (associated with young age at diagnosis,
      smoking, 5-aminosalicylic acid, and thiopurine exposure)), and non-Hodgkin
      lymphoma (SIR, 3.43; 95% CI, 1.38-7.07 (unrelated to thiopurine exposure)).
      CONCLUSIONS: Patients with CD, but not UC, have an overall excess risk of cancer.
      Clinical characteristics of IBD patients at excess risk differ by cancer subtype.

PMID- 23978955
TI  - Instability of hydrophobic and viscoelastic polymer thin films in water at room
      temperature.
AB  - The instability of a polyisoprene (PI) thin film on a silicon substrate at room
      temperature in an aqueous environment was investigated by atomic force microscopy
      and optical microscopy. The instability mechanism changes from spinodal dewetting
      to hole nucleation with increasing film thickness, with the transitional
      thickness found to be around 46-50 nm. For PI films >=50 nm, the dewetting was
      observed to proceed via successive stages of hole nucleation and growth, hole
      coalescence, cellular pattern formation and droplet formation. There is also a
      slowing down in the rate of the PI dewetting process and an increase in the
      pattern size as the film thickness is increased. In those films with observable
      holes, we also observed the coexistence of fine cellular cracking that is on a
      much smaller scale of hundreds of nanometres and extends only a few nanometres in
      depth from the film surface.

PMID- 23978953
TI  - Diagnostic delay in Crohn's disease is associated with a complicated disease
      course and increased operation rate.
AB  - OBJECTIVES: The impact of diagnostic delay (a period from appearance of first
      symptoms to diagnosis) on the clinical course of Crohn's disease (CD) is unknown.
      We examined whether length of diagnostic delay affects disease outcomes. METHODS:
      Data from the Swiss IBD cohort study were analyzed. Patients were recruited from
      university centers (68%), regional hospitals (14%), and private practices (18%).
      The frequencies of occurrence of bowel stenoses, internal fistulas, perianal
      fistulas, and CD-related surgery (intestinal and perianal) were analyzed.
      RESULTS: A total of 905 CD patients (53.4% female, median age at diagnosis 26 (20
      36) years) were stratified into four groups according to the quartiles of
      diagnostic delay (0-3, 4-9, 10-24, and >=25 months, respectively). Median
      diagnostic delay was 9 (3-24) months. The frequency of immunomodulator and/or
      antitumor necrosis factor drug use did not differ among the four groups. The
      length of diagnostic delay was positively correlated with the occurrence of bowel
      stenosis (odds ratio (OR) 1.76, P=0.011 for delay of >=25 months) and intestinal
      surgery (OR 1.76, P=0.014 for delay of 10-24 months and OR 2.03, P=0.003 for
      delay of >=25 months). Disease duration was positively associated and non-ileal
      disease location was negatively associated with bowel stenosis (OR 1.07, P<0.001,
      and OR 0.41, P=0.005, respectively) and intestinal surgery (OR 1.14, P<0.001, and
      OR 0.23, P<0.001, respectively). CONCLUSIONS: The length of diagnostic delay is
      correlated with an increased risk of bowel stenosis and CD-related intestinal
      surgery. Efforts should be undertaken to shorten the diagnostic delay.

PMID- 23978956
TI  - Teaching basic life support: a prospective randomized study on low-cost training
      strategies in secondary schools.
AB  - BACKGROUND: Cardiopulmonary resuscitation (CPR) training at school is
      recommended. Limited school resources prevent implementation. The learning
      efficacy of low-cost training strategies is unknown. OBJECTIVE: To evaluate the
      efficacy of different CPR learning strategies using low-cost didactic tools.
      METHODS: Children (n=593, 15-16 years) were randomized to four training
      conditions: (1) manikin+teacher instruction (control group), (2) manikin+video
      instruction, (3) foam dice+plastic bag+peer training+teacher instruction, and (4)
      foam dice+plastic bag+peer training+video instruction. After a 50 min training, a
      3 min CPR test on a manikin was performed using SkillReporting Software (Laerdal,
      Norway), and repeated after 6 months. The data of children without previous CPR
      training were analysed. Analysis of variance and the chi-test assessed
      differences between groups. RESULTS: Complete data sets were available for 165
      pupils. Initially, group 3 scored lower on the mean ventilation volume (P<0.05).
      The control group scored better than the alternative groups (P<0.05) on the mean
      compression rate. After 6 months, the differences disappeared. All groups scored
      equally on ventilation volume (P=0.12), compression depth (P=0.11), compression
      rate (P=0.10), correct hand position (P=0.46) and number of correct compressions
      (P=0.76). Ventilation volume was sufficient in 32% of the pupils, 18% had a
      correct compression depth and 59% had a correct compression rate. CONCLUSION:
      Training efficacy with low-cost equipment was not different from training with a
      manikin. The outcome for all training strategies was suboptimal. The basics of
      CPR can be taught with alternative equipment if manikins are not available.

PMID- 23978957
TI  - Preparedness of Belgian civil hospitals for chemical, biological, radiation, and
      nuclear incidents: are we there yet?
AB  - OBJECTIVE: As one of Europe's most densely populated countries with multiple
      nuclear installations and a prominent petrochemical industry, Belgium is at some
      reasonable risk for terrorist attacks or accidental chemical, biological,
      radiation, and nuclear (CBRN) incidents. We hypothesize that local hospitals are
      not sufficiently prepared to deal with these incidents. MATERIALS AND METHODS:
      All 138 Belgian hospitals with an emergency department (ED) were sent a survey on
      their preparedness. Data on hospital disaster planning, risk perception,
      availability of decontamination units, personal protective equipment, antidotes,
      radiation detection, infectiologists, isolation measures, and staff training were
      collected. RESULTS: The response rate was 72%. Although 71% of hospitals reported
      being at risk for CBRN incidents, only 53% planned for the same in their disaster
      plans. Only 11% of hospitals had decontamination facilities in front of or at the
      ED entrance and only 6% had appropriate personal protective equipment for triage
      and decontaminating teams. Atropine was available at all centers, but more
      specific antidotes such as hydroxycobolamine, thiosulphate, or pralidoxime were
      less available (47, 47, and 19%, respectively). Six percent of hospitals had
      radiodetection equipment with an alarm function and 14% had a nuclear specialist
      available 24/7. Infectiologists were continuously available in 26% of the total
      EDs surveyed. Individual isolation facilities were present in 36% of the EDs, and
      isolation facilities capable of housing larger groups were present in 9%.
      University hospitals were significantly better prepared than community hospitals.
      CONCLUSION: There are serious gaps in hospital preparedness for CBRN incidents in
      Belgium. Lack of financial resources is a major obstacle in achieving sufficient
      preparedness.

PMID- 23978958
TI  - Capillarics: pre-programmed, self-powered microfluidic circuits built from
      capillary elements.
AB  - Microfluidic capillary systems employ surface tension effects to manipulate
      liquids, and are thus self-powered and self-regulated as liquid handling is
      structurally and chemically encoded in microscale conduits. However, capillary
      systems have been limited to perform simple fluidic operations. Here, we
      introduce complex capillary flow circuits that encode sequential flow of multiple
      liquids with distinct flow rates and flow reversal. We first introduce two novel
      microfluidic capillary elements including (i) retention burst valves and (ii)
      robust low aspect ratio trigger valves. These elements are combined with flow
      resistors, capillary retention valves, capillary pumps, and open and closed
      reservoirs to build a capillary circuit that, following sample addition,
      autonomously delivers a defined sequence of multiple chemicals according to a
      preprogrammed and predetermined flow rate and time. Such a circuit was used to
      measure the concentration of C-reactive protein. This work illustrates that as in
      electronics, complex capillary circuits may be built by combining simple
      capillary elements. We define such circuits as "capillarics", and introduce
      symbolic representations. We believe that more complex circuits will become
      possible by expanding the library of building elements and formulating abstract
      design rules. 

PMID- 23978959
TI  - Enzyme replacement therapy on hypophosphatasia mouse model.
AB  - Hypophosphatasia (HPP) is an inborn error of metabolism caused by deficiency of
      the tissue-nonspecific alkaline phosphatase (TNSALP), resulting in a defect of
      bone mineralization. Natural substrates for this ectoenzyme accumulate
      extracellulary including inorganic pyrophosphate (PPi), an inhibitor of
      mineralization, and pyridoxal 5-phosphate (PLP), a co-factor form of vitamin B6.
      Enzyme replacement therapy (ERT) for HPP by functional TNSALP is one of the
      therapeutic options. The C-terminal-anchorless human recombinant TNSALP derived
      from Chinese hamster ovary cell lines was purified. TNSALP-null mice (Akp2 (-/-)
      ), an infantile model of HPP, were treated from birth using TNSALP and vitamin B6
      diet. Long-term efficacy studies of ERT consisted of every 3 days subcutaneous or
      intravenous injections till 28 days old (dose 20 U/g) and subsequently every 3
      days intravenous injections for 6 months (dose 10 U/g). We assessed therapeutic
      effect by growth and survival rates, fertility, skeletal manifestations, and
      radiographic and pathological finding. Treated Akp2 (-/-) mice grew normally till
      4 weeks and appeared well with a minimum skeletal abnormality as well as absence
      of epilepsy, compared with untreated mice which died by 3 weeks old. The
      prognosis of TNSALP-treated Akp2 (-/-) mice was improved substantially: 1)
      prolonged life span over 6 months, 2) improvement of the growth, and 3) normal
      fertility. After 6 months of treatment, we found moderate hypomineralization with
      abnormal proliferative chondrocytes in growth plate and articular cartilage. In
      conclusion, ERT with human native TNSALP improves substantial clinical
      manifestations in Akp2 (-/-) mice, suggesting that ERT with anchorless TNSALP is
      also a potential therapy for HPP. 

PMID- 23978960
TI  - Linkage between coenzyme a metabolism and inflammation: roles of pantetheinase.
AB  - Pantetheinase is an enzyme hydrolyzing pantetheine, an intermediate of the
      coenzyme A degradation pathway. Pantetheinase has long been considered as the
      enzyme that recycles pantothenic acid (vitamin B5) generated during coenzyme A
      breakdown. Genetic analyses showed that mammals have multiple genes known as
      vanin family genes. Recent studies using mice lacking the vanin-1 gene
      (pantetheinase gene) suggest that pantetheinase is actively involved in the
      progression of inflammatory reactions by generating cysteamine. Additional
      studies using human leukocytes demonstrate that human neutrophils have abundant
      pantetheinase proteins on the surface and inside the cells. The second
      pantetheinase protein, GPI-80/VNN2, is suggested to work as a modulator of the
      function of Mac-1 (CD11b/CD18), an adhesion molecule important to neutrophil
      functions. This review delineates the characteristics of the pantetheinase/vanin
      gene family and how they affect inflammation. 

PMID- 23978961
TI  - In vivo imaging and histochemistry are combined in the cryosection labelling and
      intravital microscopy technique.
AB  - Intravital microscopy has been used extensively to study dynamic processes in the
      context of a living animal; however, only a limited number of fluorescent probes
      and mouse models are available. By contrast, many dyes and antibodies exist for
      the immuno-labelling of fixed tissue. Here we report a method that combines the
      advantages of histochemistry and in vivo imaging by correlating cryosection
      labelling with corresponding intravital microscopy images (CLIM). Using CLIM, we
      find that the presence of CD3(+) T cells correlates with mammary tumour cell
      migration. When CD4(+) and CD8(+) T-cell subsets are depleted, reduced tumour
      cell migration is observed. From these data we conclude that CLIM is a powerful
      tool to correlate intravital microscopy data with cryosection labelling data. 

PMID- 23978962
TI  - Extrapulmonary tuberculosis, epidemiology and patterns in Saudi Arabia.
AB  - Annual incidence rates of extrapulmonary tuberculosis have been increasing over
      the last few years in the Kingdom of Saudi Arabia. True rates may even be higher
      due to incomplete reporting. Diagnosis of this condition requires high clinical
      suspicion, special diagnostic procedures, special staining, and culture media for
      acid fast bacilli. Delayed diagnosis results in increasing morbidity, mortality,
      and cost to the health care system. Particularly in areas of high endemicity of
      Mycobacterium tuberculosis, clinicians should be aware of the various forms of
      extrapulmonary tuberculosis. The available epidemiology and patterns of various
      forms of extrapulmonary tuberculosis in the Kingdom of Saudi Arabia are presented
      in this review. 

PMID- 23978963
TI  - Magnetic resonance imaging and Neuro-Behcet Disease.
AB  - Behcet disease is a rare multi-system immune related vasculitis which may involve
      the central nervous system, usually during the course of the illness. Magnetic
      resonance imaging is currently the modality of choice for the detection of the
      parenchymal lesions in their different phases, as well as the dural sinus venous
      thrombosis. 

PMID- 23978964
TI  - Epidemiology of neonatal meningitis in Qatar.
AB  - OBJECTIVE: Neonatal meningitis is responsible for thousands of neonatal deaths
      annually all over the world. Our study was conducted to determine the
      epidemiology, management and best preventive measures for neonatal meningitis in
      Qatar. METHODS: A retrospective study reviewed the records of bacterial
      meningitis patients under the age of one month. The study was carried out at
      Hamad Medical Hospital, the only hospital that provides health care at Qatar and
      the study period was between January 1998 to December 2000. RESULTS: Thirteen
      patients were included. Sixty percent of patients had early onset meningitis.
      Causative organisms were group B Streptococcus pneumoniae, Klebsiella pneumonia,
      Pseudomonas species, Neisseria meningitidis, Staphylococcus epidermidis and
      Flavibacterium meningococcus septicum. A bacterial resistance to the usual
      combination of ampicillin and gentamicin were noticed (as initial treatment
      before culture sensitivity results), which affected negatively on some patients.
      Complications of cerebral palsy, mental retardation and epilepsy occurred in 3
      patients (23%). None of the patients died during the study period. CONCLUSION:
      Emphasis is placed on the importance of correct early diagnosis and appropriate
      antibiotic therapy. It is suggested that the identification and appropriate
      treatment of any maternal bacterial infection is an important measure in
      preventing neonatal sepsis and meningitis.

PMID- 23978965
TI  - Profile of childhood meningitis in a hospital in South West Saudi Arabia.
AB  - OBJECTIVE: To study the pattern of meningitis in children admitted to King Faisal
      Military Hospital, Aseer region, Kingdom of Saudi Arabia, during the period 1987
      through to 2000. Particular emphasis was on Hemophilus influenzae meningitis.
      METHODS: All the patients between the age of one month and 13 years of age, who
      were diagnosed with meningitis during that period, using the International
      Classification of Disease 9 coding system, were included in this study. RESULTS:
      A total of 43 cases of meningitis based on the cerebrospinal fluid results were
      found. The majority (74%) of these cases were less than 2-years of age. Twenty
      four patients had a positive cerebrospinal fluid culture. Fifteen of them (62.5%)
      were due to Hemophilus influenzae. The others were due to Streptococcus
      pneumoniae, Klebsiella pneumoniae, Staphylococcus aureus and Group B
      streptococcus. The remaining 19 patients had cerebrospinal fluid findings
      consistent with bacterial meningitis. CONCLUSION: Meningitis due to Hemophilus
      influenzae, constitutes a large percentage of childhood meningitis in the Kingdom
      of Saudi Arabia. This increase is highly attributed to the lack of vaccination
      against this organism. We recommend introducing this vaccine as a part of the
      routine vaccination schedule for all children.

PMID- 23978966
TI  - Meningococcal meningitis epidemic. A new role for single-dose oily
      chloramphenicol.
AB  - OBJECTIVE: To compare the orthodox use of 5 days crystalline penicillin and an
      alternate regime of single intramuscular injection of long acting oily
      chloramphenicol during the 1999 cerebrospinal meningitis epidemic that occurred
      in Abu Jubeha, South Kordofan, Sudan. METHODS: All 793 patients with
      meningococcal meningitis admitted to Abu Jubeha hospital in the eastern parts of
      South Kordofan State, were investigated. Through a quasi-experimental design some
      140 patients were treated with crystalline penicillin for 5 days while the
      remaining majority, after the exhaustion of penicillin stocks, were put on single
      dose intramascular injections of oily long-acting chloramphenicol. RESULTS: Males
      were slightly more affected than females (1.3:1), mean age affected was 17.2
      years, the majority being below 20 years of age (68%) while 27.3% were below 10
      years. The peak of the epidemic was during late March and early April namely 9th
      and 10th epidemic weeks. In the penicillin group 87.1% recovered uneventfully,
      6.4% died, 2.1% developed blindness and 1.5% partial deafness. In the
      chloramphenicol group, full recovery was reported in 92.8%, 5% fatalities,
      blindness in 0.5%, partial deafness in 0.3% and skin necrosis in 0.1%.
      CONCLUSION: The study suggests the use of single-dose intramascular injections of
      oily chloramphenicol as a nationwide antibiotic of choice for future meningitis
      epidemics in view of not only its efficacy, but also its low cost, easiness of
      use, stability and safety.

PMID- 23978967
TI  - Guillain-Barre syndrome. Pattern of muscle weakness.
AB  - OBJECTIVE: The objective of this study was to determine the pattern of muscle
      weakness in patients with Guillain-Barre Syndrome. METHODS: In a cross-sectional
      study, 50 Iraqi patients aged one to 60 years diagnosed with Guillain-Barre
      Syndrome according to Asbury criteria, admitted in 5 Neurological Centers in
      Baghdad, Iraq between October 1997 and October 1999, were studied for pattern of
      muscle weakness by clinical evaluation of power using scale from 0-5. RESULTS: In
      80% of patients, muscle weakness started in lower limbs while at presentation 4
      limb weakness was the most frequent (96%). It was found that the upper extremity
      weakness was mainly distal in 73% of patients, while lower extremity weakness was
      mainly proximal in 68%. Weakness in extremities associated with cranial nerve
      involvement occurred in 72% of patients. Trunk muscles were involved in 34%.
      Various modes of spread of muscle weakness were seen in this study but the
      ascending variety was the most common occurring in 78% of patients and it was
      characterized by upward spread, however, contiguous parts of the body were not
      always successively involved. CONCLUSION: Upper extremity weakness was mainly
      distal while lower extremity weakness was mainly proximal and there is
      predilection for trunk muscle involvement that is quite unusual in other types of
      polyneuropathy. Therefore, all patients with suspected Guillain-Barre Syndrome
      should be examined carefully for pattern of muscle weakness in extremities, which
      may be helpful in differential diagnosis especially in early stages of the
      disease.

PMID- 23978968
TI  - Evoked and event related potentials in chronic respiratory failure.
AB  - OBJECTIVE: To assess the value of brainstem auditory evoked potentials and event
      related evoked potential (3rd positive component of evoked related potentials
      with latency of 300 millisecond, in evaluating cognitive dysfunction in patients
      with chronic respiratory failure. METHODS: Thirty-two patients with chronic
      obstructive pulmonary disease and respiratory failure of mild to moderate
      severity, were assessed regarding their mental function, utilizing mini-mental
      state examination, arterial blood gases including PH, partial pressure of carbon
      dioxide, partial pressure of oxygen, and both brainstem auditory evoked
      potentials and event related evoked potential response. Twenty-five normal
      subjects, matched for age and sex, were also studied as a control group. The
      study was carried out during the year 1999 to 2000 in 3 hospitals; King Khalid
      University Hospital, King AbdulAziz University Hospital and Sahara Hospital,
      Riyadh, Kingdom of Saudi Arabia. RESULTS: There were significant delay of event
      related evoked potential response in patients compared with controls (P<0.05). No
      significant difference was noted for brainstem auditory evoked potentials and
      mini-mental state examination scores were within normal limits in 78% of
      patients. When event related evoked potential were analyzed in comparison with
      blood gases and mini-mental state examination, there was a clear moderate
      correlation with severity of hypoxemia (r = -0.697). Correlation was also noted,
      but to a lesser degree with partial pressure of carbon dioxide (r = 0.52) and PH
      (r = 0.53). There was no correlation with mini-mental state examination.
      CONCLUSION: The significant delay of event related evoked potential, which is
      considered the neuro-physiological correlate of cognition, points clearly to the
      presence of a certain degree of mental dysfunction in many of these patients,
      namely sub-clinical encephalopathy. These subtle changes commonly evade detection
      by conventional bed side test (mini-mental state examination), while detailed
      neuropsychological assessment is cumbersome and time consuming. So, event related
      evoked potential measurement may be an objective and practical test of subtle
      cognitive dysfunction in mild respiratory failure. Unfortunately, absolute event
      related evoked potential values may not be useful in individual patients, in view
      of its wide range. However, it is probably very helpful in the assessment of a
      group of subjects, such as trials of a new therapeutic modality. A follow-up
      study utilizing a larger group of patients, and formal neuropsychological mental
      assessment, will be expected to confirm and expand the present study's
      conclusions.

PMID- 23978969
TI  - The effect of chewing Khat leaves on human mood.
AB  - OBJECTIVE: Chewing fresh leaves of the Khat plant (Catha edulis), represents a
      widespread habit with a deep-rooted sociocultural tradition in Yemen. Khat is
      chewed for its central stimulant properties and to dispel feeling of fatigue and
      its use is believed to be associated with disturbance of mood. We studied the
      effect of chewing Khat leaves on human mood by using a standard questionnaire
      method, the Hospital Anxiety and Depression scale. METHODS: A prospective study
      was conducted in the Faculty of Medicine and Health Sciences, University of
      Sana'a during the period January to June 2000. It comprised 200 healthy
      volunteers, interviewed on 2 occasions a week apart. Subjects either chewed Khat
      at least 3 hours daily for 3 days or abstained from chewing for at least 7 days
      prior to mood assessment using the Hospital Anxiety and Depression scale.
      Subjects were studied in random order. RESULTS: Using the Hospital Anxiety and
      Depression scale, there was a significant increase (P<0.0001) of median score on
      the scale indicating mood disturbance during the Khat-arm of the study as
      compared to the control-arm. The effect was particularly evident shortly after
      the Khat session. Reactive depression symptoms were predominant. CONCLUSION: Khat
      chewing did result in functional mood disorder. This effect is believed to be
      caused by the sympathomimetic action of cathinone on the central nervous system.
      The clinical implication of this study is that Khat-chewing might exacerbate
      symptoms in patients with pre-existing psychiatric disease.

PMID- 23978970
TI  - Myclonic seizures in a young girl with Fishers variant of Guillain-Barre
      syndrome.
AB  - A 10-year-old girl with Fischer's variant of acute Guillain-Barre syndrome is
      described. She had predominantly sensory involvement with autonomic dysfunction,
      ophthalmoplegia and myoclonic jerks. Myoclonus persisted for 2 weeks and the
      pupillary involvement was evident even after 2 months. The association of
      myoclonus with Guillain-Barre syndrome has not been previously reported. 

PMID- 23978971
TI  - Acute respiratory failure revealing Guillain-Barre syndrome.
AB  - This article reports the occurrence of Guillain-Barre syndrome in a critically
      ill patient manifesting as a "difficult-to-wean" patient. This uncommon but
      possible etiology is worth noting by physicians in the intensive care unit. 

PMID- 23978972
TI  - Sandhoff disease (GM2 gangliosidoses) in a premature patient with
      bronchopulmonary dysplasia.
AB  - We report a female premature infant with bronchopulmonary dysplasia and Sandhoff
      disease. The clue for diagnosis was the fundoscopy examination. We discuss this
      rare disease with unusual presentation of intrauterine growth retardation,
      premature delivery, and bronchopulmonary dysplasia. 

PMID- 23978973
TI  - Delayed traumatic epidural hematoma of the posterior fossa.
AB  - The prompt use of computerized tomography has significantly enhanced the early
      localization of traumatic posterior fossa hematoma of the brain. Consequently,
      timely surgical intervention has been possible before irreversible damage has set
      in. The result is an overall improvement in the survival of patients with this
      condition. The clinical presentations of 2 children who developed traumatic
      posterior fossa epidural hematoma after a fall and were successfully operated
      upon, are presented. Computerized tomography scan of the brain of the first child
      was carried out on the day of admission and did not show any hematoma. The
      emergency computerized tomography scan of the brain that was carried out on the
      3rd day when the patient became unresponsive localized the left epidural
      hematoma. Even though the 2nd patient was brought for treatment a week after the
      fall, his level of consciousness was good, an indication of the greatest
      prognostic factor, which with timely initiation of surgical intervention ensured
      a good outcome. 

PMID- 23978975
TI  - Clinical uses of e-mail.

PMID- 23978974
TI  - Congenital absence of the radius, scaphoid, trapezium, thumb and hypoplasia of
      the lunate.
AB  - The congenital absence of the right radius, scaphoid, trapezium, thumb and
      hypoplasia of the lunate are described in a 9-year-old boy. He had full extension
      of his elbow, while flexion motion was limited to 90 degrees. His hand was
      radially deviated. The thumb was absent. The index and middle fingers were united
      and immobile. The ring finger had movement only at the metacarpophalangeal joint,
      while the little finger had full motion. Complete blood count fell within normal
      ranges. He had no other malformations or mental retardation. No hereditary family
      history was found and there was no consanguineous marriage. This case is
      different from cases mentioned in the literature due to lunate hypoplasia and the
      anomalies of the index, middle and ring fingers. 

PMID- 23978976
TI  - Antiphospholipid antibodies associated with different presentations at a
      University Hospital.

PMID- 23978978
TI  - Message from the editors.

PMID- 23978977
TI  - Epilepsy and Ramadan fasting.

PMID- 23978979
TI  - Adaptive behavior of marine cellular clouds.
AB  - Shallow marine clouds appear in two formations - open cells that are weakly
      reflective and closed cells that are more reflective and hence more effective at
      cooling the climate system. Lagrangian satellite data analysis reveals that open
      cells oscillate, forming and disappearing with a periodicity of ~3 hours. In
      contrast, closed cells maintain rigid structures for periods of more than 10
      hours, suggesting that self-organisation breaks the link between the lifetime and
      the scale of a convective entity. These dynamical states are linked to two
      theoretical solutions of population dynamics. 

PMID- 23978980
TI  - [Associations between socioeconomic status and self-rated health in northeast
      German rural communities in 1973, 1994, and 2004/2008].
AB  - This paper reports on selected results from the study "Health and Lifestyle in
      Rural Northeast Germany". A special characteristic of this study is the regional
      focus on peripheral rural communities and the trend study design. It was analyzed
      whether, and to what extent, associations exist between socioeconomic status and
      self-rated health in this regional context and over time. Thus, regression
      analyses were conducted using equivalent income, level of school education, and
      age as independent variables and self-rated health as the dependent variable.
      Analyses are based on paper-pencil surveys of the adult residents of 14 rural
      communities chosen at random in northeast Germany, performed in 1973, 1994, and
      2004-2008. In all survey waves, a lower level of school education was associated
      with poor self-rated health. By contrast, associations between income and health
      were less consistent and constant over time. The associations between income and
      health are discussed as being specific to East Germany and as a consequence of
      social transformation in the context of reunification. 

PMID- 23978981
TI  - [Dementia Care Manager for patients with dementia. Determination of the
      requirements and qualifications contents for nurses in the DelpHi-MV study].
AB  - Dementia is one of the most prevalent chronic progressive diseases in older age.
      The progression of dementia is associated with an increasing demand for patient
      care. Thus, the nursing profession fulfills important tasks in the supply of care
      in dementia. Care of dementia patients requires nurses with more specialized
      professional knowledge. Consequently, the development of new qualification
      concepts in dementia is needed. Therefore, the German Center for
      Neurodegenerative Diseases, Rostock/Greifswald, has developed a qualification
      according to the Dementia Care Management concept. A prospective cross-sectional
      study identified the tasks and qualifications of nurses as Dementia Care
      Managers. Overall, 27 tasks and 28 qualification items were identified for a
      nurse to qualify as a Dementia Care Manager. In the next step, the first version
      of the Dementia Care Management Curriculum was developed. 

PMID- 23978982
TI  - [Sport as a means to prevention, rehabilitation, and health promotion. An expert
      opinion].
AB  - Physical activities are particularly health effective when they are structured
      and systematically organized, for example, with respect to a dose-response
      relationship or to psychosocial aspects. Which insights can be gained from
      scientific knowledge on the structure of physical activities? Which health
      related goals can be sought with different physical activities in the field of
      sport? Which target groups can be reached with these kinds of sport? These
      questions are addressed in this article on the basis of current scientific
      knowledge-to promote the development of health-enhancing physical activities
      especially in sport federations, but also to create a communication platform
      between the sport and the health sector. The work of researchers in this field is
      focused mainly on health-enhancing physical activity, but they are also engaged
      in health-related scientific organizations and in sport federations. 

PMID- 23978983
TI  - [Factors influencing the uptake of vaccines by adolescents with migration
      background. A qualitative study of adolescents, mothers, and physicians].
AB  - One of the special challenges in immunization policy is communication and access
      to adolescents. To identify barriers and enablers for the immunization of this
      specific target group, we conducted 11 focus group discussions with adolescents
      with and without migration background, mothers with Turkish and Russian migration
      background, and physicians in private practice in March 2011. The results showed
      that for adolescents, the utilization of immunization was guided by informational
      and organizational processes in families and by the consulting physician. The low
      awareness of immunization-related issues that was observed among adolescents is
      especially challenging, because routine visits to the doctor often stop with the
      transition from pediatric to adult health care. Immigration-related factors may
      additionally affect the utilization of immunization services. Besides improving
      access to information and lowering the barriers to immunization for adolescents
      in general, culturally sensitive interventions may be a promising approach for
      improving communication between mothers and the immunizing physician and thereby
      improving vaccination coverage in the adolescent target group. 

PMID- 23978984
TI  - [Methods of evidence mapping. A systematic review].
AB  - BACKGROUND: Evidence mapping is an increasingly popular approach to
      systematically evaluate published research. While there are methodological
      standards for systematic reviews, discrepancies exist between the terminology and
      methods used within evidence mapping. AIM: The aim of this systematic review is
      to describe the methodology and terminology used in evidence mapping and to
      demonstrate the continuum between evidence mapping and traditional systematic
      reviews. METHODS: A systematic literature search was conducted in 10 databases in
      order to obtain a comprehensive picture of the state of the research standards
      for evidence mapping. In addition, websites of institutions which are already
      conducting evidence mapping were searched. RESULTS: The included study pool (n =
      12) shows that the terms 'evidence map' and 'scoping review' are widely used
      within evidence mapping. Evidence maps are an approach to depict both the number
      and characteristics of studies in tabular form that exist as well as evidence
      gaps based on primary studies and systematic reviews of broad clinical questions.
      Scoping reviews also summarize the literature in a tabular form but also give a
      descriptive narrative summary of the results. A quality assessment of the studies
      is generally not included. CONCLUSION: Evidence mapping allows the identification
      of research gaps. This aspect is particularly important for interventions which
      are used without sufficient evidence. In contrast, systematic reviews are mainly
      used to estimate effects for interventions and evaluate whether the included
      studies are reliable.

PMID- 23978985
TI  - Papal chemistry challenge.

PMID- 23978986
TI  - Solution to Certified Reference Material recipe challenge.

PMID- 23978987
TI  - Phase II trial of gemcitabine and S-1 for patients with advanced pancreatic
      cancer.
AB  - PURPOSE: To evaluate the efficacy and safety of combined gemcitabine and S-1 as
      first-line chemotherapy for patients with locally advanced or metastatic
      pancreatic cancer. METHODS: This study included patients who had been diagnosed
      with unresectable, locally advanced or metastatic adenocarcinoma arising from the
      pancreas, which was histologically or cytologically confirmed and involved at
      least 1 unidimensionally measurable lesion. The regimen consisted of intravenous
      1,000 mg/m(2) gemcitabine on day 1 and 8 combined with oral S-1 on days 1-14
      every 21 days. The dosage of S-1 was based on the body surface area (BSA) as
      follows: 40 mg bid (total 80 mg/day) for a BSA of <1.25, 50 mg bid (total 100
      mg/day) for a BSA of >=1.25 but <1.5, and 60 mg bid (total 120 mg/day) for a BSA
      of >=1.5. Treatment consisted of at least 2 courses unless rapid disease
      progression was noted. The primary end points were the response and disease
      control rates, and the secondary end points were toxicity and survival. RESULTS:
      Thirty-seven patients were enrolled between August 2005 and December 2010. The
      median number of chemotherapy cycles was 4 (range 1-28 cycles). Response to
      treatment could be evaluated in 31 patients. None of the patients showed complete
      response, but 5 achieved partial response. The response rate was thus 13.5 % [95
      % confidence interval (CI) 2.7-24.3 %] in the intent-to-treat population. Sixteen
      patients (43.2 %; 95 % CI 27-59.5 %) showed stable disease, and the overall
      disease control rate was 56.8 % (95 % CI 40.6-72.9 %). For all 37 patients, the
      median progression-free survival was 4.6 months (95 % CI 1.8-7.6 month), and the
      median overall survival was 9.4 month (95 % CI 5.8-12.6 month). Chemotherapy
      related grade 3/4 hematological toxicities were neutropenia (36.1 %), leucopenia
      (22.2 %), and anemia (13.9 %). The non-hematological toxicities were generally
      mild. CONCLUSIONS: Combination chemotherapy with gemcitabine and S-1 was
      effective, convenient, and safe in patients with advanced pancreatic cancer.

PMID- 23978988
TI  - Efficacy and safety of everolimus in Korean patients with metastatic renal cell
      carcinoma.
AB  - PURPOSE: Few studies have investigated the effects of everolimus therapy in Asian
      populations. This study evaluates the safety and efficacy of everolimus in Korean
      patients with metastatic renal cell carcinoma (mRCC). METHODS: We retrospectively
      reviewed records of Korean patients with mRCC (n = 22) who received everolimus
      between January 2009 and July 2010 and evaluated them for efficacy and safety.
      RESULTS: One patient achieved a partial response, and 16 patients had stable
      disease, corresponding to an overall response rate of 4.5 % and a disease control
      rate of 77.3 %. Median progression-free survival was 5.4 months (95 % CI 0.9
      9.8). Median overall survival was not reached. Univariate analysis showed that
      Memorial Sloan-Kettering Cancer Center risk (P = .004), thrombocytopenia (P =
      .018), hyperglycemia (P = .007) and hypertriglyceridemia (P = .041) were
      associated with disease progression. The most common adverse events (AEs) were
      hypertriglyceridemia and anemia, similar to Western patients. Creatinine and
      aspartate aminotransferase levels were higher than those reported for Western
      patients. The most common grade >=3 AEs in this study were hypertriglyceridemia
      and anemia, compared with lymphopenia (14 %) in Western patients. CONCLUSIONS:
      Safety of everolimus in Korean mRCC patients differed from that reported in
      Western patients. Therefore, liver function enzymes, hemoglobin levels, lipid
      profile and chest CT scans should be monitored more closely in Asian mRCC
      patients receiving everolimus.

PMID- 23978989
TI  - Pharmacokinetics and antineoplastic activity of galectin-1-targeting OTX008 in
      combination with sunitinib.
AB  - PURPOSE: OTX008 is a galectin-1-targeting compound, currently undergoing a phase
      I clinical trial. This study aimed at investigating OTX008 pharmacokinetics (PK)
      and antineoplastic activity. METHODS: Pharmacokinetics and activity of OTX008
      were analyzed in the human ovarian carcinoma A2780-1A9 and glioblastoma U87MG
      xenografted in nude mice. In vitro, OTX008 was tested on tumor and endothelial
      cells. RESULTS: After 5 mg/kg i.v., OTX008 achieved plasma Cmax of 14.39 MUg/mL,
      distributed rapidly, and was eliminated with a half-life of 31.4 h. Tumor OTX008
      Cmax (1.65 MUg/g, 1.76 MUM), achieved at 0.5 h, remained high at 24 h (0.516
      MUg/g, 0.55 MUM) with AUC of 15.76 MUg/g*h. OTX008 accumulated in the tumor after
      repeated administrations achieving a concentration of 2.3 MUM, compatible with
      the concentrations active in vitro. OTX008 (5 mg/kg i.v., every other day for 3
      weeks) inhibited the in vivo growth of A2780-1A9, whereas U87MG was not
      sensitive. In vitro, OTX008 affected endothelial cell proliferation, motility,
      invasiveness, and cord formation. Tumor cell proliferation was also inhibited,
      with differences in sensitivity among cell lines (IC50 from 1 to 190 MUM). OTX008
      potentiated the activity of the tyrosine kinase inhibitor sunitinib on A2780-1A9
      in vivo and in vitro, where the combination showed synergistic (endothelial
      cells) and additive (A2780-1A9) antiproliferative activity, indicating that the
      combination targets both the tumor and vascular compartments. CONCLUSIONS: OTX008
      alone or in combination with sunitinib-has a favorable PK and antineoplastic
      activity on selected tumor models through the effects on both endothelial and
      tumor cells.

PMID- 23978991
TI  - Laparoscopic and perineal approaches to perineal hernia repair.
AB  - BACKGROUND: Perineal hernias after abdominoperineal resection (APER) of the
      rectum appear to be becoming more common, but there only a small number of
      reported cases, with very few reports discussing more than one or two. There is
      little consensus as to the optimal method of repair. We report the successful
      management of 7 cases of postoperative perineal hernia, including a hernia around
      a gluteal rotation flap that has not previously been reported, and discuss the
      operative approaches. METHODS: We performed a single-centre hospital database
      review over 6 years. RESULTS: Seven perineal hernias occurred after APER and were
      repaired. Six were treated with a transabdominal approach (5 laparoscopic and 1
      laparoscopic converted to open) and one perineal approach. In 4 cases, a
      synthetic composite mesh was used, in 2 a biological mesh and in one direct
      suture repair. There have been no recurrences during a median follow-up of 25
      months. CONCLUSIONS: Laparoscopic mesh repair of symptomatic perineal hernia is
      the method of choice in most cases. Herniation may still occur despite inset of a
      gluteal rotation flap at initial APER and laparoscopic repair in that instance is
      difficult.

PMID- 23978992
TI  - Half-encapsulated Au nanoparticles by nano iron oxide: promoted performance of
      the aerobic oxidation of 1-phenylethanol.
AB  - Au nanoparticles half-encapsulated in nano iron oxide are prepared and loaded on
      alumina as a support. The donation of electrons from nano iron oxide to Au
      nanoparticles is detected and both the properties of gold and iron oxide are
      adjusted by the donation. The properties are different from the bulk iron oxide
      supported gold catalysts, in which the iron oxide is little influenced by the
      electronic interaction between the two components. The catalyst shows noticeably
      promoted activity for the aerobic oxidation of 1-phenylethanol over Au-Al2O3 and
      Au-bulk FeOx. The enhanced catalytic behavior may result from the cooperative
      effect between the Au nanoparticles and nano iron oxide. 

PMID- 23978990
TI  - Evidence of recessive Alzheimer disease loci in a Caribbean Hispanic data set:
      genome-wide survey of runs of homozygosity.
AB  - IMPORTANCE The search for novel Alzheimer disease (AD) genes or pathologic
      mutations within known AD loci is ongoing. The development of array technologies
      has helped to identify rare recessive mutations among long runs of homozygosity
      (ROHs), in which both parental alleles are identical. Caribbean Hispanics are
      known to have an elevated risk for AD and tend to have large families with
      evidence of inbreeding. OBJECTIVE To test the hypothesis that the late-onset AD
      in a Caribbean Hispanic population might be explained in part by the homozygosity
      of unknown loci that could harbor recessive AD risk haplotypes or pathologic
      mutations. DESIGN We used genome-wide array data to identify ROHs (>1 megabase)
      and conducted global burden and locus-specific ROH analyses. SETTING A whole
      genome case-control ROH study. PARTICIPANTS A Caribbean Hispanic data set of 547
      unrelated cases (48.8% with familial AD) and 542 controls collected from a
      population known to have a 3-fold higher risk of AD vs non-Hispanics in the same
      community. Based on a Structure program analysis, our data set consisted of
      African Hispanic (207 cases and 192 controls) and European Hispanic (329 cases
      and 326 controls) participants. EXPOSURE Alzheimer disease risk genes. MAIN
      OUTCOMES AND MEASURES We calculated the total and mean lengths of the ROHs per
      sample. Global burden measurements among autosomal chromosomes were investigated
      in cases vs controls. Pools of overlapping ROH segments (consensus regions) were
      identified, and the case to control ratio was calculated for each consensus
      region. We formulated the tested hypothesis before data collection. RESULTS In
      total, we identified 17 137 autosomal regions with ROHs. The mean length of the
      ROH per person was significantly greater in cases vs controls (P = .0039), and
      this association was stronger with familial AD (P = .0005). Among the European
      Hispanics, a consensus region at the EXOC4 locus was significantly associated
      with AD even after correction for multiple testing (empirical P value 1 [EMP1],
      .0001; EMP2, .002; 21 AD cases vs 2 controls). Among the African Hispanic subset,
      the most significant but nominal association was observed for CTNNA3, a well
      known AD gene candidate (EMP1, .002; 10 AD cases vs 0 controls). CONCLUSIONS AND
      RELEVANCE Our results show that ROHs could significantly contribute to the
      etiology of AD. Future studies would require the analysis of larger, relatively
      inbred data sets that might reveal novel recessive AD genes. The next step is to
      conduct sequencing of top significant loci in a subset of samples with
      overlapping ROHs. 

PMID- 23978993
TI  - Posterior vertebral column resection in early onset spinal deformities.
AB  - PURPOSE: Early onset spinal deformities (EOSD) can be life-threatening in very
      young children. In the growing spine, surgical intervention is often unavoidable
      and should be carried out as soon as possible. A deformed section of the spine
      not only affects the development of the remaining healthy spine, but also that of
      the chest wall (which influences pulmonary function), the extremities and body
      balance. Posterior vertebral column resection (PVCR) represents an effective
      surgical solution to address such problems. However, reports in the literature
      concerning PVCR are mostly limited to its use in adolescents or adults. The
      purpose of this study was to illustrate our experience with PVCR in EOSD and to
      describe the surgical technique with respect to the unique anatomy of young
      children. MATERIALS AND METHODS: Four children [mean age 3.7 (range 2.5-5.2)
      years] with severe spinal deformity underwent PVCR through a single approach.
      Multimodal intraoperative monitoring was used in all cases. Surgery included one
      stage posterior circumferential resection of one vertebral body along with the
      adjoining intervertebral discs and removal of all posterior elements. A
      transpedicular screw-rod system was used for correction and stabilisation. Fusion
      was strictly limited to the resection site, allowing for later conversion into a
      growing rod construct at the remaining spine, if necessary. Relevant data were
      extracted retrospectively from patient charts and long spine radiographs.
      RESULTS: The mean operation time was 500 (range 463-541) min, with an estimated
      blood loss of 762 (range 600-1,050) ml. Mean follow-up time was 6.3 (range 3.5
      12.4) years. After PVCR, the mean Cobb angle for scoliosis was reduced from 69
      degrees  (range 50-99 degrees ) to 29 degrees  (5-44 degrees ) and the sagittal
      curvature (kyphosis) from 126 degrees  (87-151 degrees ) to 61 degrees  (47-75
      degrees ). The mean correction of scoliosis was 57 % (18-92 degrees ) and of
      kyphosis, 51 % (44-62 degrees ). There were no spinal cord-related complications.
      In three patients, spinal instrumentation for growth guidance (fusion less
      growing rod technique) was applied. Two patients had complications: one patient
      had a complication of anesthesia, halo pin failure, and revision surgery with
      extension of the instrumentation cranially due to loss of correction; the second
      patient had a postoperative infection, which required plastic reconstructive
      measures. CONCLUSION: PVCR appears to be an effective technique to treat severe
      EOSD. There are important differences in its use in young children when compared
      with older patients. In patients with EOSD, additional surgical procedures are
      often necessary during growth, and hence non-fusion instrumentation beyond the
      vertebral resection site is advantageous, as it permits spinal growth and the
      later addition of fusion.

PMID- 23978995
TI  - Reviewer's comment concerning "3D analysis of brace treatment in idiopathic
      scoliosis" (ESJO-D-12-00300R" by A. Courvoisier, X. Drevelle, R. Vialle, J.
      Dubousset and W. Skalli).

PMID- 23978994
TI  - Advances in the diagnosis of degenerated lumbar discs and their possible clinical
      application.
AB  - PURPOSE: One possible source of chronic low back pain is a degenerated
      intervertebral disc. In this review, various diagnostic methods for the
      assessment of the presence of degenerative changes are described. These include
      clinical MRI, a number of novel MRI techniques and nuclear magnetic resonance
      spectroscopy. METHODS: Non-systematic literature review. RESULTS: Clinical MRI is
      the most commonly employed technique to determine the general "health status" of
      the intervertebral disc. Novel MRI techniques, such as quantitative MRI, T1rho
      MRI, sodium MRI and nuclear magnetic resonance spectroscopy, are more sensitive
      in quantifying the biochemical changes of disc degeneration, as measured by
      alteration in collagen structure, as well as water and proteoglycan loss. As
      potential future diagnostic alternatives, miniature sensors are currently being
      developed to measure parameters associated with the disc degeneration cascade,
      such as intradiscal pressure and PG concentration. However, none of the methods
      listed above show sufficient specificity to identify a degenerated disc as the
      actual source of the pain. Provocative discography is the only test aimed at a
      direct diagnosis of discogenic pain, but it has a high false positive rate and
      there is some evidence of long-term adverse effects. Imaging techniques have also
      been tested for this purpose, but their validity has not been confirmed and they
      do appear to be problematic. CONCLUSIONS: A reliable diagnostic tool that could
      help a clinician to determine if a disc is the source of the pain in patients
      with chronic LBP is still not available. New MRI techniques are under
      investigation that could result in a significant improvement over current
      methods, particularly as they can allow monitoring, not only of morphological but
      also of biochemical changes.

PMID- 23978996
TI  - Transvertebral anterior cervical foraminotomy: midterm outcomes of clinical and
      radiological assessments including the finite element method.
AB  - PURPOSE: The aim of this study was to compare the clinical features, radiological
      changes, biomechanical effects, and efficacy in patients treated by
      transvertebral anterior foraminotomy. Preservation of segmental motion and
      avoidance of adjacent segment degeneration are theoretical advantages of
      transvertebral anterior foraminotomy. In practice, this procedure is minimally
      invasive and has shown good clinical results, especially in patients with
      unilateral cervical radiculopathy. METHOD: We conducted a retrospective minimum 2
      year follow-up study of the cervical spine of patients treated by transvertebral
      anterior foraminotomy at our institution. Radiological outcomes, which were
      estimated by measuring disc and functional spinal unit heights, and the angle and
      range of motion (ROM) from C2 to C7 of the functional spinal unit and adjacent
      segments were evaluated. Furthermore, a three-dimensional finite element method
      was used to biomechanically analyze the strength of the postoperative vertebral
      body. RESULTS: Between 2004 and 2009, 34 patients underwent surgery. The
      improvement rate was 94.2 %. The average flexion-extension ROM from C2 to C7 was
      36.6 +/- 16.6 degrees . On plain radiographs, the disc height and ROM and height
      of the functional spinal unit in the operated segment were not significantly
      decreased relative to the preoperative levels. The finite element method also
      revealed that there was no difference in strength between the pre- and
      postvertebral bodies. CONCLUSIONS: These results demonstrate that biomechanical
      stability was achieved. Transvertebral anterior cervical foraminotomy did not
      limit motion in the operated and adjacent segments and did not cause a
      significant decrease in disc and vertebral heights after surgery.

PMID- 23978998
TI  - Estimating number of diagnosed persons living with HIV in the United States
      engaged in unprotected serodiscordant risk behavior with unsuppressed viral load.

PMID- 23978997
TI  - Correlates of elevated interleukin-6 and C-reactive protein in persons with or at
      high risk for HCV and HIV infections.
AB  - BACKGROUND: HIV and hepatitis C virus (HCV) infections may increase interleukin-6
      (IL-6) and C-reactive protein (CRP). However, relationships between inflammatory
      biomarkers, chronic viral infections, clinical factors, and behavioral factors
      remain poorly understood. METHODS: Using linear regression, we modeled cross
      sectional associations between loge IL-6 or loge CRP levels and HCV, HIV,
      injection drug use, and comorbidity among 1191 injection drug users. RESULTS:
      Mean age was 47 years, 46.0% reported currently injecting drugs, 59.0% were HCV
      monoinfected, and 27% were HCV/HIV coinfected. In multivariable models, higher
      loge IL-6 was associated with HCV monoinfection [beta = 0.191, 95% confidence
      interval (CI): 0.043 to 0.339] and HCV/HIV coinfection (beta = 0.394, 95% CI:
      0.214 to 0.574). In contrast, HCV monoinfection (beta = -0.523, 95% CI: -0.275 to
      -0.789) and HCV/HIV coinfection (beta = -0.554 95% CI: -0.260 to -0.847) were
      associated with lower CRP. Lower CRP with HCV infection was independent of liver
      fibrosis severity, synthetic function, or liver injury markers; CRP decreased
      with higher HCV RNA. Increased injection intensity was associated with higher IL
      6 (P = 0.003) and CRP (P < 0.001); increasing comorbidity (P < 0.001) and older
      age (P = 0.028) were associated with higher IL-6; older age was associated with
      higher CRP among HCV-uninfected participants (P = 0.021). CONCLUSION: HIV and HCV
      infections contribute to chronic inflammation; however, reduced CRP possibly
      occurs through HCV-mediated mechanisms. Findings highlight potentially modifiable
      contributors to inflammation.

PMID- 23978999
TI  - Trends in plasma HIV-RNA suppression and antiretroviral resistance in British
      Columbia, 1997-2010.
AB  - OBJECTIVES: To examine temporal trends in plasma viral load (pVL) suppression and
      antiretroviral resistance from 1997 to 2010 in British Columbia (BC), Canada, and
      determine characteristics, pVL ranges, and resistance profiles of HIV-positive
      individuals with unsuppressed pVL in 2010. METHODS: HIV-positive individuals >=19
      years old in the provincial database at the BC Centre for Excellence in HIV/AIDS
      were included. Virological suppression was defined as 2 consecutive pVL <500
      copies per milliliter within each calendar year. Temporal trends were evaluated
      using the Cochran-Armitage test. Persons with suppressed vs. unsuppressed pVL in
      2010 were compared using the Pearson chi2 or Fisher exact test (categorical
      variables) and the Wilcoxon rank-sum test (quantitative variables), including
      unsuppressed individuals only if they were on antiretroviral therapy (ART) in
      2010 or their baseline CD4 count was <350 cells per cubic millimeter or <500
      cells per cubic millimeter, in separate analyses. RESULTS: The proportion of
      individuals with suppressed pVL increased from 24% to 80% (P < 0.001). In
      comparative analyses, individuals with unsuppressed pVL (877 of 6142) were more
      likely to be female (30% vs. 16%), younger (median, 43 vs. 48 years), have
      injection drug use history (38% vs. 30%), report Aboriginal ancestry (30% vs.
      16%), and have hepatitis C coinfection (57% vs. 34%) (all P < 0.001). Similar
      patterns were observed using the <500 cells per cubic millimeter CD4 cutoff. The
      median pVL of all unsuppressed individuals in 2010 was 12,896 copies per
      milliliter (interquartile range, 1495-47,763). CONCLUSIONS: The proportion of
      individuals achieving pVL suppression in BC has increased markedly since 1997;
      however, further efforts are needed to maximize the individual and societal
      benefits of modern antiretroviral therapy.

PMID- 23979000
TI  - HIV infection is associated with diffusing capacity impairment in women.
AB  - Respiratory dysfunction is common with HIV infection, but few studies have
      directly assessed whether HIV remains an independent risk factor for pulmonary
      function abnormalities in the antiretroviral therapy era. Additionally, few
      studies have focused on pulmonary outcomes in HIV+ women. We tested associations
      between risk factors for respiratory dysfunction and pulmonary outcomes in 63
      HIV+ and 36 HIV-uninfected women enrolled in the Women's Interagency HIV Study.
      Diffusing capacity (DL(CO)) was significantly lower in HIV+ women (65.5%
      predicted vs. 72.7% predicted, P = 0.01), and self-reported dyspnea in HIV+
      participants was associated with both DL(CO) impairment and airflow obstruction.
      Providers should be aware that DL(CO) impairment is common in HIV infection, and
      that either DL(CO) impairment or airflow obstruction may cause respiratory
      symptoms in this population.

PMID- 23979002
TI  - Pharmacokinetics and safety of tenofovir in HIV-infected women during labor and
      their infants during the first week of life.
AB  - BACKGROUND: Data describing the pharmacokinetics and safety of tenofovir in
      neonates are lacking. METHODS: The HIV Prevention Trials Network 057 protocol was
      a phase 1, open-label study of the pharmacokinetics and safety of tenofovir
      disoproxil fumarate (TDF) in HIV-infected women during labor and their infants
      during the first week of life with 4 dosing cohorts: maternal 600 mg doses/no
      infant dosing; no maternal dosing/infant 4 mg/kg doses on days 0, 3, and 5;
      maternal 900 mg doses/infant 6 mg/kg doses on days 0, 3, and 5; maternal 600 mg
      doses/infant 6 mg/kg daily for 7 doses. Pharmacokinetic sampling was performed on
      cohort 1 and 3 mothers and all infants. Plasma, amniotic fluid, and breast milk
      tenofovir concentrations were determined by liquid chromatographic-tandem mass
      spectrometric assay. The pharmacokinetic target was for infant tenofovir
      concentration throughout the first week of life to exceed 50 ng/mL, the median
      trough tenofovir concentration in adults receiving standard chronic TDF dosing.
      RESULTS: One hundred twenty-two mother-infant pairs from Malawi and Brazil were
      studied. Tenofovir exposure in mothers receiving 600 and 900 mg exceeded that in
      nonpregnant adults receiving standard 300 mg doses. Tenofovir elimination in the
      infants was equivalent to that in older children and adults, and trough tenofovir
      plasma concentrations exceeded 50 ng/mL in 74%-97% of infants receiving daily
      dosing. CONCLUSIONS: A TDF dosing regimen of 600 mg during labor and daily infant
      doses of 6 mg/kg maintains infant tenofovir plasma concentration above 50 ng/mL
      throughout the first week of life and should be used in the studies of TDF
      efficacy for HIV prevention of mother-to-child transmission and early infant
      treatment.

PMID- 23979003
TI  - Confirmatory factor analysis of the Injustice Experience Questionnaire in an
      Australian compensable population.
AB  - PURPOSE: This study examined the factor structure of the Injustice Experience
      Questionnaire (IEQ; Sullivan et al. in J Occup Rehabil 18:249-261, 2008) using
      confirmatory factor analysis (CFA). Two models were proposed for analysis: a
      single factor and a two-factor model. METHODS: A total of 150 participants (81
      males and 69 females, mean age = 45.48 years, SD = 10.71), with a chronic work
      related musculoskeletal disorder (53 % back condition), and a mean duration of
      work disability of 4.34 years (SD = 5.14), completed the IEQ and measures of
      depression and anger. CFA was performed on the IEQ data using the maximum
      likelihood estimation method. RESULTS: Neither proposed model provided an
      acceptable fit; however, a good fitting model with two highly correlated factors
      and one error covariance was derived through post hoc model fitting. The two
      factors were differentially correlated to depression and duration of work
      disability, but not anger. CONCLUSIONS: The IEQ appears to be a useful tool to
      support the comprehensive psychosocial assessment of injured workers with long
      term disability secondary to a musculoskeletal disorder. In addition to
      identifying perceived injustice, the IEQ may also be used to inform the choice of
      psychological interventions. The IEQ has construct validity and generalizability
      across different populations of injured workers.

PMID- 23979001
TI  - HIV infection is associated with reduced pulmonary diffusing capacity.
AB  - INTRODUCTION: Prior studies comparing abnormalities in pulmonary function between
      HIV-infected and HIV-uninfected persons in the current era are limited.
      OBJECTIVES: To determine the pattern and severity of impairment in pulmonary
      function in HIV-infected compared with HIV-uninfected individuals. METHODS: Cross
      sectional analysis of 300 HIV-infected men and 289 HIV-uninfected men enrolled
      from 2009 to 2011 in 2 clinical centers of the Lung HIV Study. Participants
      completed pre- and postbronchodilator spirometry, diffusing capacity of the lung
      for carbon monoxide (DLCO) measurement, and standardized questionnaires. RESULTS:
      Most participants had normal airflow; 18% of HIV-infected and 16% of HIV
      uninfected men had airflow obstruction. The mean percent predicted DLCO was 69%
      in HIV-infected vs. 76% in HIV-uninfected men (P < 0.001). A moderately to
      severely reduced DLCO of <=60% was observed in 30% of HIV-infected compared with
      18% of HIV-uninfected men (P < 0.001), despite the fact that 89% of those with
      HIV were on antiretroviral therapy. A reduced DLCO was significantly associated
      with HIV and CD4 cell count in linear regression adjusting for smoking and other
      confounders. The DLCO was lowest in HIV-infected men with CD4 cell counts <200
      cells per microliter compared with those with CD4 cell counts >=200 cells per
      microliter and to HIV-uninfected men. Respiratory symptoms of cough, phlegm and
      dyspnea were more prevalent in HIV-infected patients particularly those with
      abnormal pulmonary function compared with HIV-uninfected patients. CONCLUSIONS:
      HIV infection is an independent risk factor for reduced DLCO, particularly in
      individuals with a CD4 cell count below 200 cells per microliter. Abnormalities
      in pulmonary function among HIV-infected patients manifest clinically with
      increased respiratory symptoms. Mechanisms accounting for the reduced DLCO
      require further evaluation.

PMID- 23979004
TI  - Adolescent conflict as a developmental process in the prospective pathway from
      exposure to interparental violence to dating violence.
AB  - Within a developmental psychopathology framework, the current study examined
      adolescent conflict (age 16) with families, best friends, and dating partners as
      mediators in the prospective pathway from exposure to interparental violence
      (EIPV) in early childhood (0-64 months) to dating violence perpetration and
      victimization in early adulthood (age 23). Adolescent conflict was predicted to
      partially mediate EIPV and dating violence with significant direct paths from
      EIPV to dating violence, given the extant literature on the salience of early
      childhood EIPV for later maladjustment. Participants (N = 182; 99 males, 83
      females; 67 % Caucasian, 11 % African-American, 18 % other, 4 % unreported) were
      drawn from a larger prospective study of high-risk mothers (aged 12-34 years)
      that followed their children from birth through adulthood. EIPV and adolescent
      conflict were rated from interviews with mothers and participants, and dating
      violence (physical perpetration and victimization) was assessed with the Conflict
      Tactics Scale. Path analyses showed that EIPV in early childhood (a) directly
      predicted dating violence perpetration in early adulthood and (b) predicted
      conflict with best friends, which in turn predicted dating violence perpetration.
      Although mediation of best friend conflict was not evident, indirect effects of
      EIPV to dating violence were found through externalizing behaviors in adolescence
      and life stress in early adulthood. Findings highlight that conflict with best
      friends is affected by EIPV and predicts dating violence, suggesting that it may
      be a promising target for relationship-based interventions for youth with EIPV
      histories. Furthermore, deleterious early experiences and contemporaneous risk
      factors are salient predictors of dating violence.

PMID- 23979005
TI  - Behavioral treatment for weight gain prevention among black women in primary care
      practice: a randomized clinical trial.
AB  - IMPORTANCE: Few weight loss treatments produce clinically meaningful weight loss
      outcomes among black women, particularly in the primary care setting. New weight
      management strategies are necessary for this population. Weight gain prevention
      might be an effective treatment option, with particular benefits for overweight
      and class 1 obese black women. OBJECTIVE: To compare changes in weight and
      cardiometabolic risk during a 12-month period among black women randomized to a
      primary care-based behavioral weight gain prevention intervention, relative to
      usual care. DESIGN, SETTING, AND PARTICIPANTS: Two-arm randomized clinical trial
      (the Shape Program). We recruited patients from a 6-site community health center
      system. We randomized 194 overweight and class 1 obese (body mass index
      [calculated as weight in kilograms divided by height in meters squared], 25-34.9)
      premenopausal black women aged 25 to 44 years. Enrollment began on December 7,
      2009; 12- and 18-month assessments were completed in February and October 2,
      2012. INTERVENTIONS: The medium-intensity intervention included tailored behavior
      change goals, weekly self-monitoring via interactive voice response, monthly
      counseling calls, tailored skills training materials, and a gym membership. MAIN
      OUTCOMES AND MEASURES: Twelve-month change in weight and body mass index and
      maintenance of change at 18 months. RESULTS: Participants had a mean age of 35.4
      years, a mean weight of 81.1 kg, and a mean body mass index of 30.2 at baseline.
      Most were socioeconomically disadvantaged (79.7% with educational level less than
      a college degree; 74.3% reporting annual income <$30,000). The 12-month weight
      change was larger among intervention participants (mean [SD], -1.0 [0.5] kg),
      relative to usual care (0.5 [0.5] kg; mean difference, -1.4 kg [95% CI, -2.8 to 
      0.1 kg]; P = .04). At month 12, 62% of intervention participants were at or below
      their baseline weights compared with 45% of usual-care participants (P = .03). By
      18 months, intervention participants maintained significantly larger changes in
      weight (mean difference, -1.7 kg; 95% CI, -3.3 to -0.2 kg). CONCLUSIONS AND
      RELEVANCE: A medium-intensity primary care-based behavioral intervention
      demonstrated efficacy for weight gain prevention among socioeconomically
      disadvantaged black women. A "maintain, don't gain" approach might be a useful
      alternative treatment for reducing obesity-associated disease risk among some
      premenopausal black women. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00938535.

PMID- 23979006
TI  - Early initiation of prostacyclin in portopulmonary hypertension: 10 years of a
      transplant center's experience.
AB  - BACKGROUND: Portopulmonary hypertension (PoPH) is a subgroup of Group 1 pulmonary
      arterial hypertension (PAH) with particularly poor prognosis. Delay in initiation
      of parenteral therapy may be the reason for poor outcome. METHODS: We conducted a
      prospective observational study of all patients with Group 1 PoPH evaluated at
      Henry Ford Hospital between January 2002 and July 2012. The cohort of the REVEAL
      Registry patients with PoPH was used as the comparator group. The patient
      survival rates at 5 years after diagnosis and 2 years after enrollment, treatment
      trends, and the freedom from all-cause hospitalization rates at 2 years after
      enrollment were compared using chi (2) analysis. RESULTS: Twenty-one patients
      were enrolled in the PH Clinic with PoPH from January 2002 through July 2012. Our
      patients were significantly more likely to be on prostacyclin IV at 90 days as
      compared to REVEAL PoPH patients (67 vs. 31 %; p = 0.002). Despite this, early
      outcomes were not significantly different between the groups: 2-year survival
      from enrollment (70 and 67 %, respectively; p = 0.77) and 2-year freedom from
      hospitalization (35 vs. 49 %, respectively; p = 0.29). However, 5-year survival
      from time of diagnosis was significantly higher in our cohort of PoPH patients
      (71 and 40 %, respectively; p = 0.02). CONCLUSIONS: Early initiation of
      parenteral prostacyclin therapy in PoPH patients at a single institution was
      associated with improved 5-year patient survival from diagnosis as compared to
      the REVEAL Registry of PoPH patients and allowed for clearance for transplant in
      52 % of patients within 1 year.

PMID- 23979007
TI  - Disease-free survival by treatment after a DCIS diagnosis in a population-based
      cohort study.
AB  - Randomized trials have demonstrated the efficacy of radiation and tamoxifen in
      reducing risk of second events after breast-conserving surgery (BCS) for ductal
      carcinoma in situ (DCIS), but the comparative effectiveness of mastectomy, BCS,
      and adjuvant treatments have not been established in community practice. We
      examined disease-free survival (DFS) among 1,676 DCIS cases diagnosed during 1995
      2006 in the population-based Wisconsin In Situ Cohort study. Information on
      patient and tumor characteristics, treatments, and second breast cancer events
      were collected via a comprehensive review of data from patient interviews, the
      statewide cancer registry, and pathology reports. Breast cancer DFS was evaluated
      according to treatment while adjusting for patient and tumor characteristics.
      After an average of 7.1 years of follow-up, 143 second breast cancer events
      occurred. Overall 5-year DFS was similar among women treated with ipsilateral
      mastectomy (95.6 %; 95 % CI 93.5-97.0) compared to women treated with BCS and
      radiation (94.8 %; 95 % CI 92.8-96.1), though women receiving BCS without
      radiation experienced poorer overall DFS (87.0 %; 95 % CI 80.6-91.5). Women
      treated with tamoxifen in addition to BCS and radiation had a similar risk of a
      second breast event, although the hazard ratio (HR) suggested a potential benefit
      (0.70, 95% CI 0.41-1.19). Women treated with BCS, radiation, and tamoxifen had
      comparable risk of a second event as those treated with ipsilateral mastectomy
      (HR = 1.20; 95 % CI 0.71-2.02). In this population-based sample, the use of BCS
      with radiation and tamoxifen resulted in high DFS rates comparable to those
      achieved by ipsilateral mastectomy.

PMID- 23979008
TI  - Copper microlocalisation and changes in leaf morphology, chloroplast
      ultrastructure and antioxidative response in white lupin and soybean grown in
      copper excess.
AB  - The microlocalisation of Cu was examined in the leaves of white lupin and soybean
      grown hydroponically in the presence of 1.6 (control) or 192 MUM (excess) Cu,
      along with its effect on leaf morphology, (ultra)structure and the antioxidative
      response. The 192 MUM dose led to a reduction in the total leaf area and leaf
      thickness in both species, although more strongly so in white lupin. In the
      latter species it was also associated with smaller spongy parenchyma cells, and
      smaller spaces between them, while in the soybean it more strongly reduced the
      size of the palisade parenchyma and epidermal cells. Energy-dispersive X-ray
      microanalysis showed that under Cu excess the metal was mainly localised inside
      the spongy parenchyma cells of the white lupin leaves, and in the lower epidermis
      cell walls in those of the soybean. Cu excess also promoted ultrastructural
      chloroplast alterations, reducing the photosynthetic capacity index and the green
      area of the leaves, especially in the soybean. Despite this, soybean appeared to
      be more tolerant to Cu excess than white lupin, because soybean displayed (1)
      lower accumulation of Cu in the leaves, (2) enhanced microlocalisation of Cu in
      the cell walls and (3) greater levels of induced total -SH content and superoxide
      dismutase and catalase activities that are expected for better antioxidative
      responses. 

PMID- 23979009
TI  - Stay-green trait-antioxidant status interrelationship in durum wheat (Triticum
      durum) flag leaf during post-flowering.
AB  - Three independent durum wheat mutant lines that show delayed leaf senescence or
      stay-green (SG) phenotype, SG196, SG310 and SG504, were compared to the parental
      genotype, cv. Trinakria, with respect to the photosynthetic parameters and the
      cellular redox state of the flag leaf in the period from flowering to senescence.
      The SG mutants maintained their chlorophyll content and net photosynthetic rate
      for longer than Trinakria, thus revealing a functional SG phenotype. They also
      showed a better redox state as demonstrated by: (1) a lower rate of superoxide
      anion production due to generally higher activity of the antioxidant enzymes
      superoxide dismutase and catalase in all of the SG mutants and also of the total
      peroxidase in SG196; (2) a higher thiol content that can be ascribed to a higher
      activity of the NADPH-providing enzyme glucose-6-phosphate dehydrogenase in all
      of the SG mutants and also of the NADP(+)-dependent malic enzyme in SG196; (3) a
      lower pro-oxidant activity of lipoxygenase that characterises SG196 and SG504
      mutants close to leaf senescence. Overall, these results show a general
      relationship in durum wheat between the SG phenotype and a better redox state.
      This relationship differs across the different SG mutants, probably as a
      consequence of the different set of altered genes underlying the SG trait in
      these independent mutant lines. 

PMID- 23979010
TI  - Molecular diversity of endosymbiotic Nephroselmis (Nephroselmidophyceae) in
      Hatena arenicola (Katablepharidophycota).
AB  - Hatena arenicola (Katablepharidophycota) is a single-celled eukaryote that
      temporarily possesses a chlorophyte alga of the genus Nephroselmis as an
      intracellular symbiont. In the present study, we investigated the molecular
      diversity of the endosymbiont Nephroselmis in a natural population of the host H.
      arenicola. We sequenced the host's 18S rRNA gene and the endosymbiont's plastid
      encoded 16S rRNA gene. The results indicated that almost identical strains of the
      host harbored at least three distinct strains of the algal endosymbiont
      affiliated to the clade Nephroselmis rotunda. This finding supports our previous
      hypothesis that H. arenicola and its symbiotic alga are in an early stage of
      secondary endosymbiosis. 

PMID- 23979012
TI  - Subdiffusion supports joining of correct ends during repair of DNA double-strand
      breaks.
AB  - The mobility of damaged chromatin regions in the nucleus may affect the
      probability of mis-repair. In this work, live-cell observation and distance
      tracking of GFP-tagged DNA damage response protein MDC1 was used to study the
      random-walk behaviour of chromatin domains containing radiation-induced DNA
      double-strand breaks (DSB). Our measurements indicate a subdiffusion-type random
      walk process with similar time dependence for isolated and clustered DSBs that
      were induced by 20 MeV proton or 43 MeV carbon ion micro-irradiation. As compared
      to normal diffusion, subdiffusion enhances the probability that both ends of a
      DSB meet, thus promoting high efficiency DNA repair. It also limits their
      probability of long-range movements and thus lowers the probability of mis
      rejoining and chromosome aberrations.

PMID- 23979011
TI  - Association of cerebrospinal fluid beta-amyloid 1-42, T-tau, P-tau181, and alpha
      synuclein levels with clinical features of drug-naive patients with early
      Parkinson disease.
AB  - IMPORTANCE: We observed a significant correlation between cerebrospinal fluid
      (CSF) levels of tau proteins and alpha-synuclein, but not beta-amyloid 1-42
      (Abeta1-42), and lower concentration of CSF biomarkers, as compared with healthy
      controls, in a cohort of entirely untreated patients with Parkinson disease (PD)
      at the earliest stage of the disease studied so far. OBJECTIVE: To evaluate the
      baseline characteristics and relationship to clinical features of CSF biomarkers
      (Abeta1-42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181],
      and alpha-synuclein) in drug-naive patients with early PD and demographically
      matched healthy controls enrolled in the Parkinson's Progression Markers
      Initiative (PPMI) study. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study
      of the initial 102 research volunteers (63 patients with PD and 39 healthy
      controls) of the PPMI cohort. MAIN OUTCOMES AND MEASURES: The CSF biomarkers were
      measured by INNO-BIA AlzBio3 immunoassay (Abeta1-42, T-tau, and P-tau181;
      Innogenetics Inc) or by enzyme-linked immunosorbent assay (alpha-synuclein).
      Clinical features including diagnosis, demographic characteristics, motor,
      neuropsychiatric, and cognitive assessments, and DaTscan were systematically
      assessed according to the PPMI study protocol. RESULTS: Slightly, but
      significantly, lower levels of Abeta1-42, T-tau, P-tau181, alpha-synuclein, and T
      tau/Abeta1-42 were seen in subjects with PD compared with healthy controls but
      with a marked overlap between groups. Using multivariate regression analysis, we
      found that lower Abeta1-42 and P-tau181 levels were associated with PD diagnosis
      and that decreased CSF T-tau and alpha-synuclein were associated with increased
      motor severity. Notably, when we classified patients with PD by their motor
      phenotypes, lower CSF Abeta1-42 and P-tau181 concentrations were associated with
      the postural instability-gait disturbance-dominant phenotype but not with the
      tremor-dominant or intermediate phenotype. Finally, we found a significant
      correlation of the levels of alpha-synuclein with the levels of T-tau and P
      tau181. CONCLUSIONS AND RELEVANCE: In this first report of CSF biomarkers in PPMI
      study subjects,we found that measures of CSF Abeta1-42, T-tau, P-tau181, and
      alpha-synuclein have prognostic and diagnostic potential in early-stage PD.
      Further investigations using the entire PPMI cohort will test the predictive
      performance of CSF biomarkers for PD progression

PMID- 23979013
TI  - Bimanual coordination in children: manipulation of object distance.
AB  - The performance of many everyday activities requires the coordination of the two
      upper limbs to achieve the goal of the task. Although bimanual performance has
      been studied in detail in adults, few studies have examined how children
      coordinate the movements of the two hands during symmetric and asymmetric
      bimanual prehension. With the current study, we asked younger (4-6 years, n = 14)
      and older (7-10 years, n = 16) children to complete a discrete bimanual task.
      Specifically, they reached to grasp cylinders located at near and far positions
      in either unimanual or bimanual condition. During bimanual symmetric conditions,
      participants performed movements with both hands toward two objects located at
      the same distance (both near or both far), while in the bimanual asymmetric
      conditions, they reached for objects at different distances. Results of the
      kinematic analyses indicated that the young children consistently experienced the
      "two target" effect, whereby bimanual movements were executed more slowly than
      unimanual movements to the same distance. Older children employed a hybrid
      strategy, exhibiting slower movements in bimanual congruent conditions, but
      larger non-dominant apertures in bimanual incongruent conditions. This hybrid
      strategy was hypothesized to stem from developmental changes occurring in the
      integration of sensory information around 8 years of age. While older children
      exhibited temporal and spatial coordination patterns that were similar to
      patterns reported in adults, large relative timing differences at the start and
      end of bimanual movements and considerably weaker spatial coupling were seen in
      the younger children.

PMID- 23979014
TI  - Effect of a textured insole on balance and gait symmetry.
AB  - Asymmetry of standing balance and gait is common in individuals with neurological
      disorders, and achieving symmetrical stance and gait is an important goal of
      rehabilitation. The purpose of this study was to investigate the effect of a
      novel discomfort-induced approach (that is based on using a single textured
      insole) on the alteration in the symmetry of gait and balance. Eleven healthy
      subjects (6 females and 5 males, mean age of 28.0 +/- 4.1 years) were tested
      using the Computerized Dynamic Posturography and GaitRite systems when standing
      or walking while wearing standard footwear with the textured insole positioned
      either in the left or in the right shoe, and without the insole. Significant
      immediate effect of the textured insole was seen in the outcome measures of
      static (weight bearing) and dynamic (weight symmetry index, strength symmetry)
      balance tests (p < 0.05) as well as in gait symmetry (single support and swing
      phases) (p < 0.05). The results of the study indicate that a textured insole can
      significantly modify the symmetry of stance and gait in healthy individuals.
      Pilot data from individuals with stroke also showed a reduction in the asymmetry
      of gait when walking with the single textured insole in the shoe on the
      unaffected side. This outcome provides support for future studies on the efficacy
      of the textured insole in minimizing asymmetry of gait and posture in individuals
      in need.

PMID- 23979015
TI  - Liver in a dish.
AB  - There exists a worldwide shortage of donor livers for transplant. This may not
      pose a problem in the future, as Takebe et al. have recently grown functional
      "liver buds" from stem cells in a dish. 

PMID- 23979017
TI  - A chemical logic for reprogramming to pluripotency.
AB  - Pluripotency can be experimentally induced from somatic cells by nuclear
      transfer, fusion with embryonic stem cells, or ectopic transcription factor
      induction, but attempts to recapitulate this process by chemical means alone have
      previously failed. In a recent paper published in Science, Hou et al. pursue a
      rational, albeit laborious approach to identify cocktails of small molecules
      whose treatment restores pluripotency in adult somatic cells.

PMID- 23979016
TI  - The mINO80 chromatin remodeling complex is required for efficient telomere
      replication and maintenance of genome stability.
AB  - The INO80 (inositol requiring mutant 80) chromatin remodeling complex plays
      important roles in transcriptional regulation and DNA replication and repair, and
      consists of several functional protein subunits, including the critical Ino80
      ATPase catalytic subunit. While the function of INO80 has been studied in yeast
      and mammalian cell lines, we do not know how mIno80 contributes to the
      maintenance of genome stability to prevent cancer development in mice. Here, we
      use a conditional knockout approach to explore the cellular and organismal
      functions of mIno80. Deletion of mIno80 results in profound cellular
      proliferative defects and activation of p21-dependent cellular senescence. While
      mIno80 is required for efficient repair of DNA double strand breaks, its
      depletion did not impact upon the formation of gamma-H2AX and 53BP1 DNA damage
      foci, or the activation of the ATM-CHK2-dependent DNA damage response. mIno80
      deletion inhibited the generation of single-strand DNA, resulting in defects in
      homology-directed DNA repair (HDR) at telomeres. Fragile telomeres were prominent
      in mIno80(Delta/Delta) MEFs, suggesting that chromatin remodeling is required for
      efficient telomere replication. mIno80(-/-) mouse embryos die early during
      embryogenesis, while conditional deletion of mIno80 in adult mice results in
      weight loss and premature death. In a p53(-/-) tumor-prone background, mIno80
      haploinsufficiency favored the development of sarcomas. Our studies suggest that
      the mIno80 chromatin remodeling complex plays important roles in telomere
      replication, HDR-mediated repair of dysfunctional telomeres, and maintenance of
      genome stability.

PMID- 23979018
TI  - Proliferation and differentiation of mouse embryonic stem cells lacking all
      lamins.

PMID- 23979019
TI  - Mechanisms of apoptotic phosphatidylserine exposure.
AB  - It has been a long-standing enigma which scramblase causes phosphatidylserine
      residues to be exposed on the surface of apoptotic cells, thereby facilitating
      the phagocytic recognition, engulfment and destruction of apoptotic corpses. In a
      recent paper in Science, Nagata and coworkers reveal that the scramblases Xkr8
      and its C. elegans ortholog, CED-8, are activated by caspase cleavage in
      apoptotic cells. 

PMID- 23979020
TI  - Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided
      transcriptional activator system.
AB  - Technologies allowing for specific regulation of endogenous genes are valuable
      for the study of gene functions and have great potential in therapeutics. We
      created the CRISPR-on system, a two-component transcriptional activator
      consisting of a nuclease-dead Cas9 (dCas9) protein fused with a transcriptional
      activation domain and single guide RNAs (sgRNAs) with complementary sequence to
      gene promoters. We demonstrate that CRISPR-on can efficiently activate exogenous
      reporter genes in both human and mouse cells in a tunable manner. In addition, we
      show that robust reporter gene activation in vivo can be achieved by injecting
      the system components into mouse zygotes. Furthermore, we show that CRISPR-on can
      activate the endogenous IL1RN, SOX2, and OCT4 genes. The most efficient gene
      activation was achieved by clusters of 3-4 sgRNAs binding to the proximal
      promoters, suggesting their synergistic action in gene induction. Significantly,
      when sgRNAs targeting multiple genes were simultaneously introduced into cells,
      robust multiplexed endogenous gene activation was achieved. Genome-wide
      expression profiling demonstrated high specificity of the system. 

PMID- 23979022
TI  - A contusion model of severe spinal cord injury in rats.
AB  - The translational potential of novel treatments should be investigated in severe
      spinal cord injury (SCI) contusion models. A detailed methodology is described to
      obtain a consistent model of severe SCI. Use of a stereotactic frame and computer
      controlled impactor allows for creation of reproducible injury. Hypothermia and
      urinary tract infection pose significant challenges in the post-operative period.
      Careful monitoring of animals with daily weight recording and bladder expression
      allows for early detection of post-operative complications. The functional
      results of this contusion model are equivalent to transection models. The
      contusion model can be utilized to evaluate the efficacy of both neuroprotective
      and neuroregenerative approaches.

PMID- 23979021
TI  - MicroRNA-124 mediates the cholinergic anti-inflammatory action through inhibiting
      the production of pro-inflammatory cytokines.
AB  - The vagus nerve can control inflammatory response through a 'cholinergic anti
      inflammatory pathway', which is mediated by the alpha7-nicotinic acetylcholine
      receptor (alpha7nAChR) on macrophages. However, the intracellular mechanisms that
      link alpha7nAChR activation and pro-inflammatory cytokine production remain not
      well understood. In this study, we found that miR-124 is upregulated by
      cholinergic agonists in LPS-exposed cells and mice. Utilizing miR-124 mimic and
      siRNA knockdown, we demonstrated that miR-124 is a critical mediator for the
      cholinergic anti-inflammatory action. Furthermore, our data indicated that miR
      124 modulates LPS-induced cytokine production by targeting signal transducer and
      activator of transcription 3 (STAT3) to decrease IL-6 production and TNF-alpha
      converting enzyme (TACE) to reduce TNF-alpha release. These results also indicate
      that miR-124 is a potential therapeutic target for the treatment of inflammatory
      diseases. 

PMID- 23979023
TI  - Differential activation of mTOR complex 1 signaling in human brain with mild to
      severe Alzheimer's disease.
AB  - Mammalian target of rapamycin (mTOR) signaling has been suggested to be effective
      in modifying cognitive status in animal models of Alzheimer's disease (AD), but
      little is known about its role in AD patients. We hereby tested whether mTOR
      signaling was activated and whether activated mTOR signaling was related to the
      degree of cognitive deficits in patients with AD. Autopsy brain hippocampal
      tissues were obtained from controls and patients with AD and Western blots were
      performed using antibodies against mTOR signaling molecules and RagC, an upstream
      component of mTOR complex 1 (mTORC1) signaling. We found that expression of
      mTOR/p-mTOR and its downstream targets S6/p-S6 and Raptor/p-Raptor were expressed
      in the control and AD hippocampus. The expression levels of these signaling
      molecules were significantly increased in the hippocampus at the severe stages of
      AD, compared to controls and other stages of AD. Interestingly, Rictor expression
      level was unaltered. In addition, RagC was increased in the hippocampus at the
      early, moderate, and severe stages of AD. Our data indicate that mTORC1, but not
      mTORC2, was activated in the AD brains and that the level of mTOR signaling
      activation was correlated with cognitive severity of AD patients. 

PMID- 23979024
TI  - Serum adipokine levels modified by donepezil treatment in Alzheimer's disease.
AB  - Neurotransmitter enhancement therapy with acetylcholinesterase inhibitors
      (AChEIs) is a clinically proven approach for patients with Alzheimer's disease
      (AD). Donepezil is one of the three currently approved AChEIs for treating AD
      symptoms delaying the decline in cognitive function. In addition to cholinergic
      hypofunction, there are several factors in AD pathogenesis. For example,
      adipocytokines released from adipose tissue are also thought to play a role in
      the progress of dementia. Adipokines, i.e., leptin and adiponectin, are involved
      in the modulation of certain cognitive functions in the brain. The goal of our
      study was to elucidate effects of donepezil therapy on the serum levels of
      certain adipokines, such as leptin and adiponectin in AD patients. Clinically
      diagnosed mild-to-moderate AD patients (n = 26) were involved in this open
      labeled, single-center, prospective self-control study. ApoE polymorphism, serum
      adiponectin, leptin, LDL, HDL, triglyceride levels, and BMI were determined
      before and at 12 and 24 weeks intervals of donepezil treatment, respectively.
      Twenty-four weeks of donepezil treatment induced a linear decrease of serum
      leptin levels (p = 0.013) and a linear elevation of serum adiponectin levels (p =
      0.007). BMI (p < 0.001) and abdominal circumference (p = 0.017) were
      significantly lower at 24 weeks as compared to control values. None of the other
      examined metabolic parameters were changed during the treatment period. This
      previously unrecognized serum adipokine regulating potential of donepezil may be
      relevant in its therapeutic, disease modifying effect in AD by transferring
      protective (by increasing serum adiponectin levels) and detrimental (by
      decreasing serum leptin levels) effects onto the neurodegenerative process at the
      same time. 

PMID- 23979025
TI  - Perlecan domain V inhibits amyloid-beta induced brain endothelial cell toxicity
      and restores angiogenic function.
AB  - In Alzheimer's disease (AD), amyloid-beta (Abeta) deposits in the
      cerebrovasculature can result in neurovascular dysfunction and/or cerebral
      amyloid angiopathy. The accumulation of Abeta in blood vessels can cause
      endothelial cell damage, resulting in impaired Abeta clearance by the blood-brain
      barrier. Additionally, impaired endothelial cell function can result in decreased
      angiogenesis in the brains of AD patients, affecting cognitive function. VEGF is
      a crucial mediator of angiogenesis and is deficient in AD brains thus promoting
      angiogenesis could be an important component of successful AD treatment. The C
      terminal portion of the extracellular matrix proteoglycan perlecan, Domain V
      (DV), promotes brain-derived endothelial cell proliferation and is proangiogenic
      in that it increases VEGFR2 expression and production of VEGF. In this study, we
      show that Abeta25-35 reduces proliferation of a mouse brain microvascular
      endothelial cell line (MBEC) in vitro and that DV and mouse LG3 (C-terminal
      fragment of DV) block these effects of Abeta25-35. Additionally, we show that DV
      restores the ability of MBECs to form tube-like structures on Matrigel in the
      presence of Abeta25-35 and that this is alpha5beta1 dependent. Interestingly, the
      reduction in tube-like structure formation by Abeta25-35 was not due to
      endothelial cell death, suggesting that Abeta25-35 induces the downregulation of
      a cell surface molecule required for adhesion events critical to the angiogenic
      process. We propose a model suggesting that DV works through both the alpha5beta1
      integrin receptor and VEGFR2 to increase VEGF production, causing competition
      with Abeta25-35 for VEGFR2 binding, thus ultimately increasing VEGF expression
      and restoring angiogenesis. This supports DV as a potential anti-amyloid therapy.

PMID- 23979026
TI  - A complex proinflammatory role for peripheral monocytes in Alzheimer's disease.
AB  - An impairment of the microglial catabolic mechanisms allows amyloid-beta (Abeta)
      accumulation in plaques within the brain in Alzheimer's disease (AD).
      Monocytes/macrophages (M/M) are activated in AD and migrate thorough the blood
      brain barrier (BBB) trying to improve Abeta clearing. In the attempt to shed
      light on the role of M/M in AD, these cells were analyzed in patients with AD or
      mild cognitive impairment (MCI) and in age-matched healthy controls. Results
      obtained in Abeta42-stimulated cell cultures showed that significantly higher
      percentages of inflammatory M/M (CD14+ CD16-CCR2++CX3CR1low) expressing toll like
      receptors (TLR) 2 and 4, as well as IL-6 and CCR2, a chemokine favoring M/M
      migration through the BBB, are seen in AD. Confocal microscopy suggested the
      presence of MHC-II/Abeta42 complexes on AD M/M alone. Finally, TRL3- and TLR8
      expressing and IL-23-producing M/M were increased in both AD and MCI compared to
      HC. These data indicate that M/M in AD are characterized by an inflammatory
      profile and are involved in the induction of both innate immune responses via TLR
      stimulation and of acquired immunity possibly secondarily to the presentation of
      Abeta peptides in an MHC-restricted fashion. Therapeutic approaches designed to
      interrupt these mechanism might prove beneficial. 

PMID- 23979028
TI  - Toward a more systematic understanding of bacterial virulence factors and
      establishing Koch postulates in silico.

PMID- 23979030
TI  - A chief nurse's reflections on Marathon Monday 2013.

PMID- 23979029
TI  - The interdependence of antibody C and V regions on specificity and affinity:
      significant implications for the engineering of therapeutic antibodies.

PMID- 23979027
TI  - TOC1: characterization of a selective oligomeric tau antibody.
AB  - The work presented herein addresses a specific portion of the tau pathology, pre
      fibrillar oligomers, now thought to be important pathological components in
      Alzheimer's disease and other neurodegenerative tauopathies. In previous work, we
      generated an antibody against purified recombinant cross-linked tau dimers,
      called Tau Oligomeric Complex 1 (TOC1). TOC1 recognizes tau oligomers and its
      immunoreactivity is elevated in Alzheimer's disease brains. In this report, we
      expand upon the previous study to show that TOC1 selectively labels tau oligomers
      over monomers or polymers, and that TOC1 is also reactive in other
      neurodegenerative tauopathies. Using a series of deletion mutants spanning the
      tau molecule, we further demonstrate that TOC1 has one continuous epitope located
      within amino acids 209-224, in the so-called proline rich region. Together with
      the previous study, our data indicates that TOC1 is a conformation-dependent
      antibody whose epitope is revealed upon dimerization and oligomerization, but
      concealed again as polymers form. This characterization of the TOC1 antibody
      further supports its potential as a powerful biochemical tool that can be used to
      better investigate the involvement of tau in neurodegenerative diseases. 

PMID- 23979032
TI  - A new leader for Magnet(r).

PMID- 23979031
TI  - Crossing our quality chasm: heeding the case for graduate preparation of nurse
      managers and leaders.
AB  - As outlined by the Institute of Medicine's Future of Nursing, it is expected that
      nurses in direct care will be baccalaureate prepared. What then should be the
      expectation for educating nurse managers? This article compares the Baccalaureate
      Essentials with the American Nurses Credentialing Center and American
      Organization of Nurse Executives certification examination content for nurse
      managers to evaluate if baccalaureate education prepares these leaders for
      management roles in order to provide additional support for graduate education of
      nurse managers. 

PMID- 23979033
TI  - Looking through the eyes of nursing leaders: the Boston marathon tragedy.

PMID- 23979034
TI  - Longitudinal charge nurse leadership development and evaluation.
AB  - OBJECTIVE: The study's aim was to examine longitudinal outcomes of a leadership
      program for permanent and relief charge nurse from 1996 to 2012 using action
      research and Kouzes and Posner's The Leadership Challenge conceptual frameworks.
      BACKGROUND: Charge nurses hold significant oversight of patient safety, quality,
      and team functioning. This study contributes knowledge regarding charge nurse
      leadership and organization outcomes associated with these essential roles over
      time. METHODS: Data were collected over 6 time periods using Kouzes and Posner's
      The Leadership Practices Inventory (LPI) and internally developed action research
      tools. Surveys were aligned with leadership and work environment changes to
      examine outcomes. RESULTS: Charge nurse leadership LPI mean ratings improved.
      Relief charge nurses reached similar LPI outcomes by 2012, with no statistical
      differences in mean or domain scores. Action research methods facilitated
      executive decision making during change processes. Demographics shifted with
      younger charge nurses with less practice experience serving as charge nurses in
      the most recent years. CONCLUSIONS: Charge nurse leadership reported significant
      gains despite institutional changes and uneven delivery of educational
      interventions.

PMID- 23979035
TI  - Developing a leadership laboratory for nurse managers based on lived experiences:
      a participatory action research model for leadership development.
AB  - OBJECTIVE: The aim of the pilot study was to design an innovative model of
      leadership development, Leadership Laboratory (LL), grounded in the lived
      experiences and peer best practices of 43 cross-disciplinary nurse managers.
      BACKGROUND: The Institute of Medicine/Robert Wood Johnson Foundation study, The
      Future of Nursing, reinforces the need to prepare nurses for leadership
      positions. METHODS: A 1-year participatory action research study was designed to
      develop 3 LLs involving nurse managers as participants, co-creators, and
      evaluators of the unique learning format. RESULTS: Analysis of qualitative and
      quantitative data revealed consistent and significantly positive results in
      leadership skill areas in all 3 LLs. Participants identified elements that
      distinguished LLs from traditional seminars and trainings sessions, including
      opportunities to gain from peer-to peer consultation, strategies, and support.
      CONCLUSIONS: Participants in the 1-year pilot demonstrated significant learning
      based on postsession and postproject assessments of the LLs. Data also described
      the unique attributes of a peer-driven approach to leadership development.

PMID- 23979036
TI  - Weighted staffing plans for better prediction of staffing needs.
AB  - OBJECTIVE: The aim of this study was to examine the effect of patient turnover
      and acuity on worked hours per patient day (WHPPD). BACKGROUND: An examination of
      staffing plans publically posted by Massachusetts hospitals with more than 300
      beds revealed that less than 40% were within 5% of their planned versus actual
      WHPPD. METHODS: Three years of WHPPD data collected from 14 adult acute care
      units were correlated with patient turnover and acuity data. A weight factor was
      retrospectively added to 8 paired units' planned WHPPD where correlations were
      identified. RESULTS: Twelve units (86%) showed significant correlations between
      WHPPD and patient turnover. Correlations between patient acuity and WHPPD were
      significant only at the aggregate level. After weighting WHPPD, the 8 paired
      units demonstrated a decreased variance between planned and actual WHPPD.
      CONCLUSION: Using a weight factor added to WHPPD to right size acute care medical
      surgical units may be useful for accurate staff planning and budgeting.

PMID- 23979037
TI  - California's nurse-to-patient ratios, Part 1: 8 years later, what do we know
      about nurse-level outcome?
AB  - California's nurse-to-patient ratios have been in place since 2004. The author
      reviews outcomes at the nurse level from a comprehensive literature review. Data
      suggest that increased levels of nurse staffing have resulted in greater job
      satisfaction. 

PMID- 23979038
TI  - Mapping the organization: a bibliometric analysis of nurses' contributions to the
      literature.
AB  - OBJECTIVE: The aim of this study was to map an academic hospital's nursing
      contributions to the literature using bibliometric methods. BACKGROUND: Nurse
      executives continue to search for ways to share knowledge gained in the clinical
      setting. Manuscripts from clinical nurses must increase to advance the science of
      nursing practice and nursing administration. METHODS: A search of electronic
      databases and curriculum vitae provided bibliographic data for University of
      Colorado Hospital (UCH) nurses from 1990 to 2012. Bibliometric techniques were
      used for publication counts and citation analysis. A review of the infrastructure
      supporting scholarly work was undertaken. RESULTS: A total of 191 journal
      articles, 9 books, 103 book chapters, 5 manuals, and 46 manual chapters were
      published by UCH nurses. Author productivity steadily increased. Citation
      analysis indicated that the works published were used by others. The h-index for
      UCH authors was 25. The hospital culture, interdisciplinary practice, and the
      role of the research nurse scientists had an impact on study results.

PMID- 23979039
TI  - Plasmonic gold mushroom arrays with refractive index sensing figures of merit
      approaching the theoretical limit.
AB  - Localized surface plasmon resonance (LSPR)-based sensing has found wide
      applications in medical diagnosis, food safety regulation and environmental
      monitoring. Compared with commercial propagating surface plasmon resonance (PSPR)
      based sensors, LSPR ones are simple, cost-effective and suitable for measuring
      local refractive index changes. However, the figure of merit (FOM) values of LSPR
      sensors are generally 1-2 orders of magnitude smaller than those of PSPR ones,
      preventing the widespread use of LSPR sensors. Here we describe an array of
      submicrometer gold mushrooms with a FOM reaching ~108, which is comparable to the
      theoretically predicted upper limit for standard PSPR sensors. Such a high FOM
      arises from the interference between Wood's anomaly and the LSPRs. We further
      demonstrate the array as a biosensor for detecting cytochrome c and alpha
      fetoprotein, with their detection limits down to 200 pM and 15 ng ml(-1),
      respectively, suggesting that the array is a promising candidate for label-free
      biomedical sensing. 

PMID- 23979040
TI  - Synchrotron radiation X-ray fluorescence analysis of biodistribution and
      pulmonary toxicity of nanoscale titanium dioxide in mice.
AB  - Using synchrotron radiation X-ray fluorescence (SRXRF), we have examined the
      biodistribution and pulmonary toxicity of nanoscale titanium dioxide (nanoTiO2)
      in mice at the elemental level. Notably, nanoTiO2 particles were mainly retained
      in lungs after intratracheal instillation, slowly cleared and were still present
      at 3 months. Different methods of intratracheal instillation influenced the
      clearance of nanoTiO2 from lungs. NanoTiO2 interfered with the natural
      distribution of K, Ca, Fe, Cu and Zn in lungs. We have thus demonstrated that
      SRXRF provides an effective approach to investigate the distribution of metal
      nanomaterials and native metal elements in tissues and organs, which offers new
      opportunities for revealing nanotoxic mechanisms of nanomaterials. 

PMID- 23979041
TI  - A persistent metal-insulator transition at the surface of an oxygen-deficient,
      epitaxial manganite film.
AB  - The oxygen stoichiometry has a large influence on the physical and chemical
      properties of complex oxides. Most of the functionality in e.g. catalysis and
      electrochemistry depends in particular on control of the oxygen stoichiometry. In
      order to understand the fundamental properties of intrinsic surfaces of oxygen
      deficient complex oxides, we report on in situ temperature dependent scanning
      tunnelling spectroscopy experiments on pristine oxygen deficient, epitaxial
      manganite films. Although these films are insulating in subsequent ex situ in
      plane electronic transport experiments at all temperatures, in situ scanning
      tunnelling spectroscopic data reveal that the surface of these films exhibits a
      metal-insulator transition (MIT) at 120 K, coincident with the onset of
      ferromagnetic ordering of small clusters in the bulk of the oxygen-deficient
      film. The surprising proximity of the surface MIT transition temperature of
      nonstoichiometric films with that of the fully oxygenated bulk suggests that the
      electronic properties in the surface region are not significantly affected by
      oxygen deficiency in the bulk. This carries important implications for the
      understanding and functional design of complex oxides and their interfaces with
      specific electronic properties in catalysis, oxide electronics and
      electrochemistry. 

PMID- 23979042
TI  - [Emergency room management of multiple trauma : ATLS(r) and S3 guidelines].
AB  - Trauma management in the emergency room is an important part of the treatment
      chain of the severely injured. Important decisions with respect to diagnostics
      and treatment must be made under time pressure. Successful trauma management in
      the emergency room requires a hospital tailored treatment protocol. This written
      protocol needs consent from all participating disciplines and must be known by
      all members of the resuscitation team. The ATLS(r) and the recently published
      clinical practice guidelines on multiple trauma can be of help in order to
      establish or update such protocols. In order to continuously evaluate and improve
      performance in the emergency room local quality circles are needed that truly
      follow that aim. Important factors are reliability of agreement between the
      different disciplines and continuous communication of results to the team
      members. In order to be successful such quality circles need people that care. 

PMID- 23979043
TI  - [Current legal framework conditions for running and utilization of biobanks :
      part 1: legal principles].
AB  - Research biomaterial banks (biobanks) are institutions which collect and prepare
      samples of human bodily substances (e.g. cells, tissues, body fluids and isolates
      from them), store personal, health and problem-related data of donors, collate
      samples and data and make them available in a suitable form for research
      purposes. The valid legal norms for the utilization and running of biobanks are
      complex and sometimes necessitate an assessment by the legal guardian. 

PMID- 23979044
TI  - The ratio of femoral head diameter to pelvic height in the normal hips of a
      Chinese population.
AB  - OBJECTIVE: The aim of this study was to determine whether the ratio between the
      femoral head diameter and pelvic height in a Chinese population is the same as
      that found in Westerners. MATERIALS AND METHODS: Standard pelvic radiography was
      performed on a group of 187 Chinese adult subjects consisting of 81 males and 106
      females with a mean age of 40 years (21-68 years). Femoral head diameter
      (vertical distance from the femoral head-neck junction to the highest point of
      the femoral head) and pelvic height (vertical distance from the highest point of
      the iliac crest to the edge of the ischial tuberosities) were measured. RESULTS:
      There were significant differences between males and females (p < 0.001), and
      between persons of high height versus low height (p = 0.011) and medium height (p
      = 0.039). There were no significant differences between persons of different age
      (p = 0.244), body mass index (p = 0.091), or between persons of low- and medium
      height groups (p = 0.69). The overall mean ratio between the femoral head
      diameter and pelvic height was 0.215 (0.173-0.249) with a 95 % CI = 0.214-0.217.
      The mean ratios in males and females were 0.221 (0.194-0.249) and 0.211 (0.173
      0.238), respectively. CONCLUSION: The mean ratio in Chinese population was
      similar to the reported ratio in a western population (about 1:5). We suggest
      that Chinese surgeons may be able to use the Crowe classification to classify
      patients with hip dysplasia.

PMID- 23979046
TI  - Magnetic resonance imaging of vascular encephalopathy related to pregnancy.
AB  - Brain lesions related to pregnancy are not frequent, but are potentially lethal.
      About half of the cases are intracerebral hemorrhage, subarachnoid hemorrhage,
      infarction, and venous thrombosis. Their imaging characteristics are not much
      different from those caused by other reasons than pregnancy, and can be
      relatively easily recognized. The other half of cases are encephalopathy related
      to pregnancy-induced hypertension, eclampsia, and other factors. Such pregnancy
      related vascular encephalopathy can be grossly sorted into 3 categories:
      posterior reversible encephalopathy syndrome, HELLP (hemolysis-elevated liver
      enzymes-low platelets) syndrome, and reversible cerebral vasoconstriction
      syndrome. These conditions are rare, but neurosurgeons must be able to recognize
      them. 

PMID- 23979045
TI  - Management of eclampsia and stroke during pregnancy.
AB  - To establish the etiologies and therapeutic strategies for the treatment of
      eclampsia and stroke during pregnancy, we performed a questionnaire-based study
      of stroke during pregnancy in Aichi prefecture (2005-2009). This study revealed
      the following findings: 66% of deliveries were managed in primary medical
      institutions, 40% of eclampsia episodes and 31% of strokes occurred at primary
      medical institutions, and 19% of strokes occurred at home. Home-onset strokes
      displayed a mortality rate of 40%. Using the results of this questionnaire, we
      investigated cases of eclampsia and/or stroke during pregnancy and revealed
      important issues regarding their management. In pregnant women with eclampsia or
      stroke, accurate antihypertensive and anticonvulsive treatment are necessary.
      Discriminating between eclampsia and stroke during labor is difficult. However,
      when facial or arm muscle weakness or a facial deficit is detected, stroke should
      be strongly suspected. Brain computed tomography can usually detect most cases of
      hemorrhagic stroke. When a stroke is detected, collaborative treatment with a
      neurosurgeon should be started as soon as possible. If stroke is suspected at a
      primary medical institution, rapid maternal transport to an intensive medical
      institution is necessary. In patients whose blood pressure is greater than
      180/120 mmHg, the use of MgSO4 to decrease the risk of convulsions and reduce
      blood pressure is recommended. These findings might aid the development of
      therapeutic strategies for pregnant women with eclampsia or stroke. 

PMID- 23979047
TI  - Antithrombotic therapy for pregnant women.
AB  - Coagulability increases during pregnancy, and thromboembolism can easily occur.
      Venous thromboembolism is a cause of death in pregnant women, but arterial
      thrombosis such as ischemic stroke in pregnancy is also not uncommon. In
      pharmacotherapy for thromboembolism in pregnant women, fetal toxicity and
      teratogenicity must be carefully considered. As anticoagulants in pregnant women,
      unfractionated heparin and low-molecular-weight heparin are recommended, but
      warfarin is not recommended since it has a low molecular weight and crosses the
      placenta. Various types of new oral anticoagulant drugs have been available in
      Japan since 2011. However, the Japanese package inserts for these anticoagulants
      advise quite cautious administration in pregnant women. The guidelines on
      pregnant women include less information about antiplatelet drugs than
      anticoagulant drugs. Aspirin may cause teratogenicity and fetal toxicity, and
      perinatal mortality is increased. However, when low doses of aspirin are
      administered as antiplatelet therapy, the US Food and Drug Administration has
      assigned pregnancy category C, and treatment is relatively safe. Neurosurgeons
      and neurologists commonly encounter pregnant women with thromboembolism, such as
      ischemic stroke. Up-to-date information and correct selection of drugs are
      necessary in consultation with specialists in perinatal care. 

PMID- 23979048
TI  - Acute revascularization therapy in pregnant patients.
AB  - Ischemic stroke is uncommon during pregnancy, but decision making for acute
      revascularization therapy including intravenous recombinant tissue plasminogen
      activator (rt-PA) is difficult. The use of rt-PA remains controversial, but a
      systematic review of 16 patients (mean age 31.7 years) showed good results for
      both maternal (77.8%) and fetal (56.3%) outcomes. Pregnancy alone is not a solid
      contraindication for acute revascularization therapy including rt-PA. An
      endovascular approach might be beneficial for reducing the hemorrhagic
      complication; however, the treatment strategy should be considered based on the
      available treatment facility. Close cooperation with obstetrics is essential for
      the successful management of saving the lives of both the mother and the fetus. 

PMID- 23979049
TI  - Anesthetic management of pregnant women with stroke.
AB  - Stroke during pregnancy is rare, but after occurring, most patients develop
      serious neurological conditions. Hemorrhagic stroke, including intracerebral
      hemorrhage and subarachnoid hemorrhage, often requires emergency surgical
      intervention. In addition to significant maternal physiological changes, the
      potential for fetal harm should be considered during anesthetic management of
      these patients. Whether cesarean section or neurosurgical intervention should be
      prioritized or performed simultaneously in pregnant women with stroke is an
      important issue. Whether the patients receive general or spinal and epidural
      anesthesia is another clinically significant issue. Finally neurosurgeons,
      anesthesiologists, and obstetricians should cooperate to manage pregnant women
      with stroke. 

PMID- 23979050
TI  - Endovascular treatment in pregnancy.
AB  - There is an increased risk of stroke during pregnancy and the puerperium.
      Decisions should be made immediately upon transfer to each institution,
      particularly with respect to when and how to treat the patient. This review
      highlights the feasibility of endovascular treatment in pregnancy. Most of the
      pharmaceutical agents and therapeutic devices used in clinical practice can be
      utilized in pregnant patients. Comprehensive information on the benefits and
      risks of treatment should be explained to the patient and her family, with
      particular attention to the safety of the mother and fetus. Radiation exposure to
      the fetus is also a concern; the hazard can be minimized with optimal protection.
      Several studies have demonstrated that conventional procedures do not cause
      serious radiation exposure exceeding the threshold of safety to the fetus.
      Endovascular therapy can be safely performed for the treatment of acute stroke as
      in non-pregnant patients with adequate attention to pharmaceutical agents and
      shielding from radiation. In contrast to therapy for acute stroke, preventive
      endovascular treatment for asymptomatic lesions remains controversial. Several
      conditions, such as cerebral aneurysms and arteriovenous malformations, are known
      to bleed more frequently in pregnancy, but whether the benefits of preventive
      treatment outweigh the associated risks is unknown. The decision for preventive
      treatment should be carefully made on a case-by-case basis after extensive
      discussion with the patient. 

PMID- 23979051
TI  - Subarachnoid hemorrhage from intracranial aneurysms during pregnancy and the
      puerperium.
AB  - Subarachnoid hemorrhage (SAH) due to the rupture of an intracranial aneurysm (IA)
      is a rare but serious complication of pregnancy and is responsible for important
      morbidity and mortality during pregnancy. This study reviewed reports of ruptured
      IA during pregnancy and the puerperium, and our own cases of ruptured IA in
      pregnant women. Hemorrhage occurred predominantly during the third trimester of
      pregnancy, when maternal cardiac output and blood volume increase and reach
      maximum. Physiological and hormonal changes in pregnancy are likely to affect the
      risk of IA rupture. Ruptured IAs during pregnancy should be managed based on
      neurosurgical considerations, and the obstetrical management of women with
      ruptured IAs should be decided according to the severity of SAH and the
      gestational age. Emergent cesarean section followed by clipping or coiling of
      aneurysms is indicated if the maternal condition and the gestational age allow
      such interventions. Although SAH during pregnancy can result in disastrous
      outcomes, the necessity of intracranial screening for high-risk pregnant women is
      still controversial. 

PMID- 23979052
TI  - Cavernous malformations in pregnancy.
AB  - Cavernous malformation is a relatively rare disease, but is important in the
      etiology of cerebral hemorrhage in pregnant and puerperal women. The risk of
      bleeding is particularly high in patients with a previous history of bleeding,
      patients with a family history of cavernous malformations, and patients with the
      causative cerebral cavernous malformation gene. Cavernous malformations are more
      likely to bleed or to increase in size during pregnancy, under the influence of
      female hormones and vascular growth factors such as vascular endothelial growth
      factor. We report our strategy for the treatment of cavernous malformations in
      pregnant women, with reference to the relevant literature. Asymptomatic patients
      and those with mild symptoms are usually followed up conservatively by magnetic
      resonance imaging, without active treatment, but surgical treatment is indicated
      in patients with severe or progressive symptoms; surgery should also be
      considered in patients with mild symptoms having risk factors for bleeding. If
      surgical treatment is selected, the operation plan needs to be devised in
      collaboration with the specialties of anesthesiology and obstetrics and
      gynecology, rather than by the brain surgeon alone, in view of the possibility of
      occurrence of complications specific to pregnant women, such as complications
      related to weight gain and difficulty in securing the airway, which develop
      during the perioperative period. 

PMID- 23979053
TI  - Moyamoya disease in pregnancy: a single institute experience.
AB  - Moyamoya disease is a rare chronic, occlusive cerebrovascular disease
      characterized by bilateral steno-occlusive changes at the terminal portion of the
      internal carotid artery and an abnormal vascular network at the base of the
      brain. Moyamoya disease particularly affects children and young adults with
      female predominance, thus pregnant patients with moyamoya disease are not
      uncommon. Among 4,400 patients with consecutive deliveries in our hospital, 6
      patients (0.14%) aged from 24 to 40 years (mean 32.7 years) were found to have
      moyamoya disease, all of whom underwent cesarean section. Four patients who had
      been diagnosed with moyamoya disease before pregnancy did not show neurological
      events in pregnancy and puerperium, but two patients who were newly diagnosed or
      progressed during the perinatal period suffered neurological deterioration due to
      ischemic stroke. Surgical revascularization at the subacute stage relieved their
      symptoms and they did not suffer permanent neurological deficit. We recommend
      that pregnant patients with moyamoya disease should be carefully managed under
      the collaboration of obstetricians and neurosurgeons, and that the procedure of
      the delivery should selected by the obstetricians to avoid unfavorable sequelae
      caused by hyperventilation and/or blood pressure elevation. 

PMID- 23979054
TI  - Pregnancy and delivery management in patients with cerebral arteriovenous
      malformation: a single-center experience.
AB  - We described pregnancy and delivery management in 9 patients with cerebral
      arteriovenous malformation (AVM). Six patients presented with intracerebral
      hemorrhage (ICH) during pregnancy (first hemorrhagic episode); 2 patients
      presented with headache; and 1 patient with incidental detection of AVM. In the 3
      patients with unruptured AVM, the diagnosis was made before pregnancy. In 3 of 6
      patients who presented with ICH, AVM removal was performed during pregnancy. One
      patient required emergency surgery for the mass effect of the hematoma, and 2
      patients with Spetzler-Martin grade I and II AVMs underwent elective surgery for
      the prevention of rebleeding. Radiosurgery for multiple AVMs was performed after
      delivery in one patient. Surgical resection and radiosurgery were performed after
      abortion in two patients. Of 3 patients with unruptured AVM, 2 patients became
      pregnant after radiosurgery and conservative treatment was initiated in 1 patient
      for Spetzler-Martin grade V AVM. Cesarean section was performed in 5 patients
      (one with severe uncontrollable pregnancy-induced hypertension) and vaginal
      delivery in 2 patients (one with grade V AVM). Delivery by obstetrical indication
      was possible in patients who underwent AVM resection during pregnancy. No
      rebleeding during pregnancy occurred. The maternal outcome was good except for
      the 2 patients with consequences of the initial ICH. The fetal outcome was good
      except for 2 cases of abortion. Pregnancy and delivery management in patients
      with AVM was successful in our institution. Early surgical intervention for AVM
      presenting as ICH during pregnancy could prevent rebleeding and improve the
      maternal and fetal prognosis. 

PMID- 23979056
TI  - Optimizing disease progression study designs for drug effect discrimination.
AB  - Investigate the possibility to directly optimize a clinical trial design for
      statistical power to detect a drug effect and compare to optimal designs that
      focus on parameter precision. An improved statistic derived from the general
      formulation of the Wald approximation was used to predict the statistical power
      for given trial designs of a disease progression study. The predicted value was
      compared, together with the classical Wald statistic, to a type I error-corrected
      model-based power determined via clinical trial simulations. In a second step, a
      study design for maximal power was determined by directly maximizing the new
      statistic. The resulting power-optimal designs and their corresponding
      performance based on empirical power calculations were compared to designs
      focusing on parameter precision. Comparisons of empirically determined power and
      the newly developed statistic, showed excellent agreement across all scenarios
      investigated. This was in contrast to the classical Wald statistic, which
      consistently over-predicted the reference power with deviations of up to 90 %.
      Designs maximized using the proposed metric differed from traditional optimal
      designs and showed equal or up to 20 % higher power in the subsequent clinical
      trial simulations. Furthermore, the proposed method was used to minimize the
      number of individuals required to achieve 80 % power through a simultaneous
      optimization of study size and study design. The targeted power of 80 % was
      confirmed in subsequent simulation study. A new statistic was developed, allowing
      for the explicit optimization of a clinical trial design with respect to
      statistical power. 

PMID- 23979057
TI  - Image analysis of pubic bone for sex determination in a computed tomography
      sample.
AB  - Radiology has demonstrated great utility for sex determination, but most studies
      are based in metrical and morphological methods in order to perform an
      identification profile. It is presented an easy image analysis-based method aimed
      to demonstrate the relationship between the bony tissue ultrastructure and sex by
      using several grey level histogram variables obtained from computed tomography
      images using sagittal sections of the pubic symphysis surface and the body of the
      pubis. The CT sample consisted of 169 hospital DICOM archives of known sex and
      age. The multivariate binary logistic regression models calculated showed
      reliabilities for sex determination between 87.4 and 95.8 %, with a high intra
      and inter-observer agreement. The suggested method is not only considered useful
      to perform an identification profile during Virtopsy, but even for application in
      further studies in order to attach a quantitative correlation for tissue
      ultrastructure characteristics without complex and expensive methods beyond image
      analysis. 

PMID- 23979058
TI  - Population genetics of 29 autosomal STRs and 17 Y-chromosomal STRs in a
      population sample from Afghanistan.
AB  - In this study, allele frequencies for 29 autosomal short tandem repeats (STRs)
      and haplotype frequencies for 17 Y-chromosomal STRs of an Afghan population have
      been generated. Samples from 348 men and women originating from Afghanistan were
      analysed for the autosomal STRs, and the combined match probability was estimated
      to be 7.5 * 10(-37). One hundred and sixty-nine men were analysed for the Y
      chromosomal STRs, which resulted in 132 different haplotypes and a haplotype
      diversity of 0.995.

PMID- 23979060
TI  - Culturable heterotrophic bacteria associated with healthy and bleached
      scleractinian Madracis decactis and the fireworm Hermodice carunculata from the
      remote St. Peter and St. Paul Archipelago, Brazil.
AB  - We report on the first characterization of the culturable heterotrophic bacteria
      of the scleractinian Madracis decactis. In addition, we characterized the
      culturable bacteria associated with the fireworm Hermodice carunculata, observed
      predating partially bleached coral colonies. Our study was carried out in the
      remote St. Peter and St. Paul Archipelago (SPSPA), Mid-Atlantic Ridge, Brazil. We
      constituted a 403 isolates collection and subsequently characterized it by means
      of pyrH and 16S rRNA partial sequences. We identified Photobacterium, Bacillus,
      and Vibrio species as members of the culturable microbiota of healthy M.
      decactis. V. campbellii, V. harveyi, V. communis, and V. maritimus were the most
      commonly found Vibrio species in healthy corals, representing more than 60 % of
      all vibrio isolates. Most of the vibrios isolated from the fireworm's tissues (n
      = 143; >90 %) were identified as V. shiloi. However, we did not recover V. shiloi
      from bleached M. decactis. Instead, we isolated V. communis, a novel
      Photobacterium species, Bacillus, Kocuria, and Pseudovibrio, suggesting a
      possible role of other facultative anaerobic bacteria and/or environmental
      features (such as water quality) in the onset of bleaching in SPSPA's M.
      decactis. 

PMID- 23979059
TI  - Co-expression of CD44+/RANKL+ tumor cells in the carcinogenesis of oral squamous
      cell carcinoma.
AB  - Receptor activator of nuclear factor-kappa (RANK)/receptor activator of nuclear
      factor-kappa B ligand (RANKL) signaling helps putative cancer stem cells (CSC) to
      maintain their stemness. Expression of CD44 and RANKL was analyzed in oral
      squamous cell carcinoma specimen (n = 191). Moreover, RANKL expression was
      measured in cancer cell lines (BICR3, BICR56) by immunohistochemistry and western
      blot analysis. Scanned images were digitally analyzed using ImageJ and the
      immunomembrane plug-in. CD44 and RANKL expression on protein level was correlated
      with clinical characteristics and impact on survival. RANKL was co-labeled with
      CD44 in immunohistochemical and immunofluorescence double labeling experiments.
      Although high CD44+/RANKL+ co-expression was significantly associated with
      clinicopathological factors and worse survival, multivariate analysis did not
      demonstrate high CD44+/RANKL+ co-expression as independent prognostic factor.
      Immunohistochemical and immunofluorescence double labeling experiments revealed
      RANKL expression by CD44+ cancer cells. RANKL specificity was confirmed by
      western blot analysis. For the first time, this study provides evidence that
      RANKL expression in OSCC might be associated with disease recurrence and a cell
      compartment measured by CD44+/RANKL+ co-expression within the mucosal epithelial
      basal layer cells. 

PMID- 23979061
TI  - A coevolving model based on preferential triadic closure for social media
      networks.
AB  - The dynamical origin of complex networks, i.e., the underlying principles
      governing network evolution, is a crucial issue in network study. In this paper,
      by carrying out analysis to the temporal data of Flickr and Epinions-two typical
      social media networks, we found that the dynamical pattern in neighborhood,
      especially the formation of triadic links, plays a dominant role in the evolution
      of networks. We thus proposed a coevolving dynamical model for such networks, in
      which the evolution is only driven by the local dynamics-the preferential triadic
      closure. Numerical experiments verified that the model can reproduce global
      properties which are qualitatively consistent with the empirical observations. 

PMID- 23979063
TI  - The thymic medulla: who needs it?

PMID- 23979064
TI  - Not practicing what we preach.

PMID- 23979062
TI  - Impact of cardiovascular risk factors on vessel wall inflammation and calcified
      plaque burden differs across vascular beds: a PET-CT study.
AB  - To evaluate the effect of age, gender and cardiovascular risk factors on vessel
      wall inflammation and the calcified plaque burden in different vascular beds as
      assessed by PET/CT. 315 patients (mean age: 57.8 years, 123 male and 192 female)
      who underwent whole body 18F-FDG PET/CT examinations were included in the study.
      Blood pool-corrected standardised uptake value (TBR) and the calcified plaque
      score (CPS, grade 0-4) were determined in the thoracic and abdominal aorta, both
      common carotid and both iliac arteries. The following cardiovascular risk factors
      were documented: Age >=65 years (n = 114), male gender (n = 123), diabetes (n =
      15), hyperlipidemia (n = 62), hypertension (n = 76), body mass index (BMI) >= 30
      (n = 38), current smoker (n = 32). Effects of risk factors on TBR and CPS in
      different arterial beds were assessed using multivariate regression analysis. In
      the thoracic aorta TBR was independently associated with age >=65 years and male
      gender, CPS was independently associated with age >=65 years, male gender,
      hypertension and diabetes. In the abdominal aorta, TBR was independently
      associated with age >=65 years and male gender, CPS with age >=65 years, diabetes
      and smoking. Independent associations in the carotid arteries were found for age
      >=65 years, male gender and BMI >= 30 in TBR and for age >=65 and diabetes in
      CPS. In the iliac arteries, TBR was independently associated with age >=65 and
      CPS with age >=65, male gender, hypertension, diabetes and smoking. Findings of
      this PET/CT study demonstrate that the impact of cardiovascular risk factors on
      vessel wall inflammation and calcified plaque burden differs across vascular
      territories. Overall, CPS was more closely associated with cardiovascular risk
      factors compared to TBR. 

PMID- 23979068
TI  - Live imaging of apoptotic cell clearance during Drosophila embryogenesis.
AB  - The proper elimination of unwanted or aberrant cells through apoptosis and
      subsequent phagocytosis (apoptotic cell clearance) is crucial for normal
      development in all metazoan organisms. Apoptotic cell clearance is a highly
      dynamic process intimately associated with cell death; unengulfed apoptotic cells
      are barely seen in vivo under normal conditions. In order to understand the
      different steps of apoptotic cell clearance and to compare 'professional'
      phagocytes--macrophages and dendritic cells to 'non-professional'--tissue
      resident neighboring cells, in vivo live imaging of the process is extremely
      valuable. Here we describe a protocol for studying apoptotic cell clearance in
      live Drosophila embryos. To follow the dynamics of different steps in
      phagocytosis we use specific markers for apoptotic cells and phagocytes. In
      addition, we can monitor two phagocyte systems in parallel: 'professional'
      macrophages and 'semi-professional' glia in the developing central nervous system
      (CNS). The method described here employs the Drosophila embryo as an excellent
      model for real time studies of apoptotic cell clearance.

PMID- 23979069
TI  - Factor structure for autism spectrum disorders with toddlers using DSM-IV and DSM
      5 criteria.
AB  - With the publication of the Diagnostic and Statistical Manual of Mental Disorders
      Fifth Edition, autism spectrum disorders are defined by two symptom clusters
      (social communication and restricted/repetitive behaviors) instead of the current
      three clusters. The current study examined the structure of the Baby and Infant
      Screen for Children with aUtIsm Traits (BISCUIT). First, an exploratory factor
      analysis was replicated whose results were largely comparable to the previous
      findings. Then, confirmatory factor analyses compared a two and three factor
      structure for the BISCUIT. Measures of model fit supported both the two and three
      factor models relatively well. When directly compared, the three factor model was
      found to be preferred over the two factor model. Implications are discussed. 

PMID- 23979070
TI  - Physicians' diagnostic accuracy, confidence, and resource requests: a vignette
      study.
AB  - IMPORTANCE: Little is known about the relationship between physicians' diagnostic
      accuracy and their confidence in that accuracy. OBJECTIVE: To evaluate how
      physicians' diagnostic calibration, defined as the relationship between
      diagnostic accuracy and confidence in that accuracy, changes with evolution of
      the diagnostic process and with increasing diagnostic difficulty of clinical case
      vignettes. DESIGN, SETTING, AND PARTICIPANTS: We recruited general internists
      from an online physician community and asked them to diagnose 4 previously
      validated case vignettes of variable difficulty (2 easier; 2 more difficult).
      Cases were presented in a web-based format and divided into 4 sequential phases
      simulating diagnosis evolution: history, physical examination, general diagnostic
      testing data, and definitive diagnostic testing. After each phase, physicians
      recorded 1 to 3 differential diagnoses and corresponding judgments of confidence.
      Before being presented with definitive diagnostic data, physicians were asked to
      identify additional resources they would require to diagnose each case (ie,
      additional tests, second opinions, curbside consultations, referrals, and
      reference materials). MAIN OUTCOMES AND MEASURES: Diagnostic accuracy (scored as
      0 or 1), confidence in diagnostic accuracy (on a scale of 0-10), diagnostic
      calibration, and whether additional resources were requested (no or yes).
      RESULTS: A total of 118 physicians with broad geographical representation within
      the United States correctly diagnosed 55.3% of easier and 5.8% of more difficult
      cases (P < .001). Despite a large difference in diagnostic accuracy between
      easier and more difficult cases, the difference in confidence was relatively
      small (7.2 vs 6.4 out of 10, for easier and more difficult cases, respectively)
      (P < .001) and likely clinically insignificant. Overall, diagnostic calibration
      was worse for more difficult cases (P < .001) and characterized by overconfidence
      in accuracy. Higher confidence was related to decreased requests for additional
      diagnostic tests (P = .01); higher case difficulty was related to more requests
      for additional reference materials (P = .01). CONCLUSIONS AND RELEVANCE: Our
      study suggests that physicians' level of confidence may be relatively insensitive
      to both diagnostic accuracy and case difficulty. This mismatch might prevent
      physicians from reexamining difficult cases where their diagnosis may be
      incorrect.

PMID- 23979071
TI  - [New aspects of prevention of nosocomial infections by multi-resistant
      organisms].

PMID- 23979072
TI  - [Nodular granuloma of the lip. An unusual manifestation of secondary syphilis].
AB  - Syphilis is a sexually transmitted disease caused by Treponema pallidum which
      evolves through three overlapping stages. A 50-year-old woman presented with an
      expanding painless granulomatous nodule on her lower lip in combination with a
      maculo-papular exanthem. Both serologic studies and microscopic examination
      indicated an infection with Treponema pallidum. This case shows an unusual
      granulomatous nodular presentation of syphilis on the lower lip, emphasizing the
      variable clinical and histological manifestations syphilis, which shows an
      increasing number of new infections worldwide in recent years. 

PMID- 23979073
TI  - [Onychomycosis. Successful treatment with a 1064 nm Nd:YAG-Laser].
AB  - A 58-year-old man presented with a two-year history of progressive
      onychodystrophy of the nails of both great toes. Clinical inspection as well as
      KOH examination and culture confirmed the diagnosis of disto-lateral
      onychomycosis of both nails caused by Trichophyton rubrum). The diseased nail
      materially was mechanically debrided. In addition both nails were treated with a
      1064 nm Nd:YAG laser (spot-diameter: 5 mm; pulse-width: 0.3 ms; fluence: 12
      J/cm(2); frequency: 5 Hz; impulses: 200 per toenail). The laser therapy was
      repeated four times at intervals of 2 months. Seven months later the patient
      showed complete clearance of both nails. We here demonstrate the efficacy of the
      Nd:YAG laser in the treatment of onychomycosis. Non-ablative laser therapy may
      present a promising, effective, well-tolerated and cost-efficient option for the
      treatment of onychomycosis. Controlled studies with relevant patient collectives
      are urgently needed. 

PMID- 23979074
TI  - Status of radiotherapy in a multidisciplinary cancer board.
AB  - Multidisciplinary cancer boards (CBs) for making cancer treatment decisions have
      become popular in many countries; however, the status of radiotherapy in CBs and
      the influence of CBs on radiotherapy decisions have not been studied. To clarify
      these issues, we reviewed the minutes of our CBs from February 2010 to March
      2012, and we classified planned treatments discussed at the CBs into five
      categories and analyzed decisions concerning radiotherapy in each category. The
      fraction of cases for which radiotherapy was recommended was 536/757 (71%). These
      cases included 478 cases (63%) for which radiation therapy was planned and four
      cases (0.5%) for which radiation therapy was unexpectedly recommended. On the
      other hand, radiation therapy was canceled in 21 cases (4%) for which radiation
      therapy had been planned. This study showed that radiotherapy was discussed in
      many cases at CBs and that CBs have a great influence on decisions concerning
      radiotherapy. 

PMID- 23979075
TI  - Severe acute radiation syndrome: treatment of a lethally 60Co-source irradiated
      accident victim in China with HLA-mismatched peripheral blood stem cell
      transplantation and mesenchymal stem cells.
AB  - This is a case report of a 32-year-old man exposed to a total body dose of 14.5
      Gy gamma-radiation in a lethal (60)Co-source irradiation accident in 2008 in
      China. Frequent nausea, vomiting and marked neutropenia and lymphopenia were
      observed from 30 min to 45 h after exposure. HLA-mismatched peripheral blood stem
      cell transplantation combined with infusion of mesenchymal stem cells was used at
      Day 7. Rapid hematopoietic recovery, stable donor engraftment and healing of
      radioactive skin ulceration were achieved during Days 18-36. The patient finally
      developed intestinal obstruction and died of multi-organ failure on Day 62,
      although intestinal obstruction was successfully released by emergency bowel
      resection. 

PMID- 23979076
TI  - Evaluation of imaging performance of megavoltage cone-beam CT over an extended
      period.
AB  - A linear accelerator vendor and the AAPM TG-142 report propose that quality
      assurance testing for image-guided devices such megavoltage cone-beam CT (MV
      CBCT) be conducted on a monthly basis. In clinical settings, however,
      unpredictable errors such as image artifacts can occur even when quality
      assurance results performed at this frequency are within tolerance limits. Here,
      we evaluated the imaging performance of MV-CBCT on a weekly basis for ~ 1 year
      using a Siemens ONCOR machine with a 6-MV X-ray and an image-quality phantom.
      Image acquisition was undertaken using 15 monitor units. Geometric distortion was
      evaluated with beads evenly distributed in the phantom, and the results were
      compared with the expected position in three dimensions. Image-quality
      characteristics of the system were measured and assessed qualitatively and
      quantitatively, including image noise and uniformity, low-contrast resolution,
      high-contrast resolution and spatial resolution. All evaluations were performed
      100 times each. For geometric distortion, deviation between the measured and
      expected values was within the tolerance limit of 2 mm. However, a subtle
      systematic error was found which meant that the phantom was rotated slightly in a
      clockwise manner, possibly due to geometry calibration of the MV-CBCT system.
      Regarding image noise and uniformity, two incidents over tolerance occurred in
      100 measurements. This phenomenon disappeared after dose calibration of beam
      output for MV-CBCT. In contrast, all results for low-contrast resolution, high
      contrast resolution and spatial resolution were within their respective
      tolerances. 

PMID- 23979077
TI  - Adaptive response in human blood lymphocytes exposed to non-ionizing
      radiofrequency fields: resistance to ionizing radiation-induced damage.
AB  - The aim of this preliminary investigation was to assess whether human peripheral
      blood lymphocytes which have been pre-exposed to non-ionizing radiofrequency
      fields exhibit an adaptive response (AR) by resisting the induction of genetic
      damage from subsequent exposure to ionizing radiation. Peripheral blood
      lymphocytes from four healthy donors were stimulated with phytohemagglutinin for
      24 h and then exposed for 20 h to 1950 MHz radiofrequency fields (RF, adaptive
      dose, AD) at an average specific absorption rate of 0.3 W/kg. At 48 h, the cells
      were subjected to a challenge dose (CD) of 1.0 or 1.5 Gy X-irradiation (XR,
      challenge dose, CD). After a 72 h total culture period, cells were collected to
      examine the incidence of micronuclei (MN). There was a significant decrease in
      the number of MN in lymphocytes exposed to RF + XR (AD + CD) as compared with
      those subjected to XR alone (CD). These observations thus suggested a RF-induced
      AR and induction of resistance to subsequent damage from XR. There was
      variability between the donors in RF-induced AR. The data reported in our earlier
      investigations also indicated a similar induction of AR in human blood
      lymphocytes that had been pre-exposed to RF (AD) and subsequently treated with a
      chemical mutagen, mitomycin C (CD). Since XR and mitomycin-C induce different
      kinds of lesions in cellular DNA, further studies are required to understand the
      mechanism(s) involved in the RF-induced adaptive response. 

PMID- 23979078
TI  - Impact of flattening-filter-free techniques on delivery time for lung
      stereotactic volumetric modulated arc therapy and image quality of concurrent
      kilovoltage cone-beam computed tomography: a preliminary phantom study.

PMID- 23979080
TI  - Nitrogen-doped carbon nanomaterials as non-metal electrocatalysts for water
      oxidation.
AB  - Efficient and low-cost electrocatalysts for the oxygen evolution reaction are
      essential components of renewable energy technologies, such as solar fuel
      synthesis and providing a hydrogen source for powering fuel cells. Here we report
      that the nitrogen-doped carbon materials function as the efficient oxygen
      evolution electrocatalysts. In alkaline media, the material generated a current
      density of 10 mA cm(-2) at the overpotential of 0.38 V, values that are
      comparable to those of iridium and cobalt oxide catalysts and are the best among
      the non-metal oxygen evolution electrocatalyst. The electrochemical and physical
      studies indicate that the high oxygen evolution activity of the nitrogen/carbon
      materials is from the pyridinic-nitrogen- or/and quaternary-nitrogen-related
      active sites. Our findings suggest that the non-metal catalysts will be a
      potential alternative to the use of transition metal-based oxygen evolution
      catalysts. 

PMID- 23979079
TI  - Results for local control and functional outcome after linac-based image-guided
      stereotactic radiosurgery in 190 patients with vestibular schwannoma.
AB  - BACKGROUND: We assessed local control (LC) and functional outcome after linac
      based stereotactic radiosurgery (SRS) for vestibular schwannoma (VS). METHODS:
      Between 1998 and 2008, 190 patients with VS were treated with SRS. All patients
      had tumors <2 cm diameter. Patients received 13.5 Gy prescribed to the 80th
      isodose at the tumor margin. The primary endpoint was LC. Secondary endpoints
      were symptomatic control and morbidity. RESULTS: Median follow-up was 40 months.
      LC was achieved in 88% of patients. There were no acute reactions exceeding Grade
      I. Trigeminal nerve dysfunction was present in 21.6% (n = 41) prior to SRS. After
      treatment, 85% (n = 155) had no change, 4.4,% (n = 8) had a relief of symptoms,
      10.4% (n = 19) had new symptoms. Facial nerve dysfunction was present in some
      patients prior to treatment, e.g. paresis (12.6%; n = 24) and dysgeusia (0.5%; n
      = 1). After treatment 1.1% (n = 2) reported improvement and 6.1% (n = 11)
      experienced new symptoms. Hearing problems before SRS were present in 69.5% of
      patients (n = 132). After treatment, 62.6% (n = 144) had no change, 10.4% (n =
      19) experienced improvement and 26.9% (n = 49) became hearing impaired.
      CONCLUSION: This series of SRS for small VS provided similar LC rates to
      microsurgery; thus, it is effective as a non-invasive, image-guided procedure.
      The functional outcomes observed indicate the safety and effectiveness of linac
      based SRS. Patients may now be informed of the clinical equivalence of SRS to
      microsurgery.

PMID- 23979081
TI  - Nurse and physician agreement in the assessment of minor blunt head trauma.
AB  - OBJECTIVE: The Pediatric Emergency Care Applied Research Network (PECARN)
      traumatic brain injury (TBI) clinical prediction rules identify children with
      minor blunt head trauma who are at low risk for clinically important traumatic
      brain injuries. We measured the agreement between the registered nurse (RN) and
      physician (MD) assessments. METHODS: We performed a cross-sectional study of all
      children <18 years of age with minor blunt head trauma who presented to a single
      emergency department. RNs and MDs independently assessed each child and recorded
      age-based PECARN predictors. As symptoms can change over time, we included cases
      only when both evaluations were completed within 60 minutes. We used the kappa
      statistic to measure RN-MD agreement, with the main analysis focusing on the
      overall PECARN rule agreement. RESULTS: Of the 1624 eligible children, 1191 (73%)
      had evaluations completed by both RN and ED providers, of which 437 (37%) were in
      children <2 years of age. The median time between completions of the provider
      forms was 12 minutes (interquartile range 4-25 minutes). The overall agreement
      between the RN and MD was higher for the older children (kappa 0.55, 95%
      confidence interval 0.49-0.61 for children 2-18 years versus kappa 0.32, 95%
      confidence interval 0.23-0.41 for children <2 years). CONCLUSIONS: The overall
      agreement between RN and MD for the PECARN TBI prediction rules was moderate for
      older children and fair for younger children. Initial RN assessments should be
      verified by the MD before clinical application, especially for the youngest
      children.

PMID- 23979082
TI  - Randomized trial of plastic bags to prevent term neonatal hypothermia in a
      resource-poor setting.
AB  - OBJECTIVES: Term infants in resource-poor settings frequently develop hypothermia
      during the first hours after birth. Plastic bags or wraps are a low-cost
      intervention for the prevention of hypothermia in preterm and low birth weight
      infants that may also be effective in term infants. Our objective was to test the
      hypothesis that placement of term neonates in plastic bags at birth reduces
      hypothermia at 1 hour after birth in a resource-poor hospital. METHODS: This
      parallel-group randomized controlled trial was conducted at University Teaching
      Hospital, the tertiary referral center in Zambia. Inborn neonates with both a
      gestational age >=37 weeks and a birth weight >=2500 g were randomized 1:1 to
      either a standard thermoregulation protocol or to a standard thermoregulation
      protocol with placement of the torso and lower extremities inside a plastic bag
      within 10 minutes after birth. The primary outcome was hypothermia (<36.5 degrees
      C axillary temperature) at 1 hour after birth. RESULTS: Neonates randomized to
      plastic bag (n = 135) or to standard thermoregulation care (n = 136) had similar
      baseline characteristics (birth weight, gestational age, gender, and baseline
      temperature). Neonates in the plastic bag group had a lower rate of hypothermia
      (60% vs 73%, risk ratio 0.76, confidence interval 0.60-0.96, P = .026) and a
      higher axillary temperature (36.4 +/- 0.5 degrees C vs 36.2 +/- 0.7 degrees C, P
      < .001) at 1 hour after birth compared with infants receiving standard care.
      CONCLUSIONS: Placement in a plastic bag at birth reduced the incidence of
      hypothermia at 1 hour after birth in term neonates born in a resource-poor
      setting, but most neonates remained hypothermic.

PMID- 23979083
TI  - Primary care interventions to prevent tobacco use in children and adolescents:
      U.S. preventive services task force recommendation statement.
AB  - DESCRIPTION: Update of the 2003 U.S. Preventive Services Task Force (USPSTF)
      recommendation on primary care interventions to prevent tobacco use in children
      and adolescents. METHODS: The USPSTF reviewed the evidence on the effectiveness
      of primary care interventions on the rates of initiation or cessation of tobacco
      use in children and adolescents and on health outcomes, such as respiratory
      health, dental and oral health, and adult smoking. The USPSTF also reviewed the
      evidence on the potential harms of these interventions. POPULATION: This
      recommendation applies to school-aged children and adolescents. The USPSTF has
      issued a separate recommendation statement on tobacco use counseling in adults
      and pregnant women. RECOMMENDATION: The USPSTF recommends that primary care
      clinicians provide interventions, including education or brief counseling, to
      prevent initiation of tobacco use in school-aged children and adolescents.

PMID- 23979084
TI  - The transfer of drugs and therapeutics into human breast milk: an update on
      selected topics.
AB  - Many mothers are inappropriately advised to discontinue breastfeeding or avoid
      taking essential medications because of fears of adverse effects on their
      infants. This cautious approach may be unnecessary in many cases, because only a
      small proportion of medications are contraindicated in breastfeeding mothers or
      associated with adverse effects on their infants. Information to inform
      physicians about the extent of excretion for a particular drug into human milk is
      needed but may not be available. Previous statements on this topic from the
      American Academy of Pediatrics provided physicians with data concerning the known
      excretion of specific medications into breast milk. More current and
      comprehensive information is now available on the Internet, as well as an
      application for mobile devices, at LactMed (http://toxnet.nlm.nih.gov).
      Therefore, with the exception of radioactive compounds requiring temporary
      cessation of breastfeeding, the reader will be referred to LactMed to obtain the
      most current data on an individual medication. This report discusses several
      topics of interest surrounding lactation, such as the use of psychotropic
      therapies, drugs to treat substance abuse, narcotics, galactagogues, and herbal
      products, as well as immunization of breastfeeding women. A discussion regarding
      the global implications of maternal medications and lactation in the developing
      world is beyond the scope of this report. The World Health Organization offers
      several programs and resources that address the importance of breastfeeding (see
      http://www.who.int/topics/breastfeeding/en/). 

PMID- 23979085
TI  - A historical perspective of pediatric publications: a bibliometric analysis.

PMID- 23979087
TI  - Hospital readmission: quality indicator or statistical inevitability?

PMID- 23979086
TI  - Autistic traits in children with and without ADHD.
AB  - OBJECTIVE: To assess the implications of autistic traits (ATs) in youth with
      attention-deficit/hyperactivity disorder (ADHD) without a diagnosis of autism.
      METHODS: Participants were youth with (n = 242) and without (n = 227) ADHD and
      controls without ADHD in whom a diagnosis of autism was exclusionary. Assessment
      included measures of psychiatric, psychosocial, educational, and cognitive
      functioning. ATs were operationalized by using the withdrawn + social + thought
      problems T scores from the Child Behavior Checklist. RESULTS: A positive AT
      profile was significantly overrepresented among ADHD children versus controls
      (18% vs 0.87%; P < .001). ADHD children with the AT profile were significantly
      more impaired than control subjects in psychopathology, interpersonal, school,
      family, and cognitive domains. CONCLUSIONS: A substantial minority of ADHD
      children manifests ATs, and those exhibiting ATs have greater severity of illness
      and dysfunction.

PMID- 23979088
TI  - Caregiver-fabricated illness in a child: a manifestation of child maltreatment.
AB  - Caregiver-fabricated illness in a child is a form of child maltreatment caused by
      a caregiver who falsifies and/or induces a child's illness, leading to
      unnecessary and potentially harmful medical investigations and/or treatment. This
      condition can result in significant morbidity and mortality. Although caregiver
      fabricated illness in a child has been widely known as Munchausen syndrome by
      proxy, there is ongoing discussion about alternative names, including pediatric
      condition falsification, factitious disorder (illness) by proxy, child abuse in
      the medical setting, and medical child abuse. Because it is a relatively uncommon
      form of maltreatment, pediatricians need to have a high index of suspicion when
      faced with a persistent or recurrent illness that cannot be explained and that
      results in multiple medical procedures or when there are discrepancies between
      the history, physical examination, and health of a child. This report updates the
      previous clinical report "Beyond Munchausen Syndrome by Proxy: Identification and
      Treatment of Child Abuse in the Medical Setting" The authors discuss the need to
      agree on appropriate terminology, provide an update on published reports of new
      manifestations of fabricated medical conditions, and discuss approaches to
      assessment, diagnosis, and management, including how best to protect the child
      from further harm.

PMID- 23979089
TI  - Severe early-onset colitis revealing mevalonate kinase deficiency.
AB  - Hyperimmunoglobulinemia D is the less severe form of mevalonate kinase deficiency
      (MKD) caused by recessive inherited mutation in the mevalonate kinase gene.
      Hyperimmunoglobulinemia D is characterized by febrile attacks, often associated
      with transient digestive manifestations, such as abdominal pain, diarrhea, and
      vomiting. Here we report for the first time 2 patients with MKD revealed by
      severe neonatal colitis. Both patients had chronic bloody diarrhea and failure to
      thrive; 1 patient since the age of 1 month and the other since the age of 12
      days. Total parenteral nutrition was required. A marked elevation of acute phase
      reactants was present, and no evidence of infection was found. In patient 1,
      ileocolonoscopy revealed ulcerative colitis at the age of 5 months. Patient 2
      suffered from enterocolitis and shock, associated with multiple bowel adhesions
      at age 5 weeks; the rectosigmoidoscopy showed aphtoid lesions of the sigmoid
      colon. Pathologic findings of colonic biopsies revealed a dense polymorph
      inflammatory infiltrate associated with deep ulcerations. Febrile attacks
      occurred 2 months after the onset of digestive symptoms in patient 1, and at
      onset of disease in patient 2. Genomic sequencing of the mevalonate kinase gene
      revealed compound heterozygous mutations in both patients. Anti-interleukin-1
      agent produced long-term remission of all digestive features and laboratory
      parameters. This report emphasizes that MKD may be the cause of severe early
      onset inflammatory colitis, and must be considered by physicians, even in the
      absence of fever, after ruling out infections. Anti-interleukin-1 therapy may
      result in a dramatic improvement of MKD-related inflammatory bowel disease. 

PMID- 23979090
TI  - Pneumococcal meningitis in children: epidemiology, serotypes, and outcomes from
      1997-2010 in Utah.
AB  - BACKGROUND: After licensure of the 7-valent pneumococcal conjugate vaccine (PCV7)
      in the United States in 2000, the incidence of pediatric pneumococcal meningitis
      decreased significantly. However, cases continue to occur. It is unknown whether
      meningitis due to PCV7 and non-PCV7 serotypes causes similar morbidity and
      mortality. METHODS: We performed a retrospective cohort study of laboratory
      confirmed pneumococcal meningitis among Utah children from 1997 to 2010. We
      reviewed medical records and obtained clinical data during the acute illness and
      follow-up data on neurologic sequelae. RESULTS: Sixty-eight cases of meningitis
      were identified. PCV7 serotypes caused 64% of cases before and 25% of cases after
      licensure of PCV7 (P < .01). The age range was similar before and after PCV7
      licensure (P = .5). The overall case fatality rate was 13% and was similar among
      cases caused by PCV7 and non-PCV7 serotypes (P = .7). Children with PCV7
      serotypes were more likely to require mechanical ventilation (68% vs 34%; P <
      .01). Of all survivors, 63% had neurologic sequelae, and the proportion was
      similar after infection with PCV7 or non-PCV7 serotypes (P = .1). More than one
      half (54%) of all children who developed pneumococcal meningitis in the PCV7
      period were eligible for PCV7 and had not been immunized. CONCLUSIONS:
      Pneumococcal meningitis continues to be associated with high mortality and
      morbidity; death and neurologic sequelae are common with both PCV7 and non-PCV7
      serotype meningitis. The substantial burden of this disease and continued cases
      among unimmunized children reinforce the need for more effective immunization
      strategies and continued surveillance in the era of PCV13.

PMID- 23979091
TI  - ADHD and learning disabilities in former late preterm infants: a population-based
      birth cohort.
AB  - BACKGROUND AND OBJECTIVE: Previous studies suggest that former late preterm
      infants are at increased risk for learning and behavioral problems compared with
      term infants. These studies have primarily used referred clinical samples of
      children followed only until early school age. Our objective was to determine the
      cumulative incidence of attention deficit/hyperactivity disorder (ADHD) and
      learning disabilities (LD) in former late preterm versus term infants in a
      population-based birth cohort. METHODS: Subjects included all children born 1976
      to 1982 in Rochester, MN who remained in the community after 5 years. This study
      focused on the comparison of subjects in 2 subgroups, late preterm (34 to <37
      weeks) and term (37 to <42 weeks). School and medical records were available to
      identify individuals who met research criteria for ADHD and LD in reading,
      written language, and math. The Kaplan-Meier method was used to estimate the
      cumulative incidence of each condition by 19 years of age. Cox models were fit to
      evaluate the association between gestational age group and condition, after
      adjusting for maternal education and perinatal complications. RESULTS: We found
      no statistically significant differences in the cumulative incidence of ADHD or
      LD between the late preterm (N = 256) versus term (N = 4419) groups: ADHD
      (cumulative incidence by age 19 years, 7.7% vs 7.2%; P = .84); reading LD (14.2%
      vs 13.1%; P = .57); written language LD (13.5% vs 15.7%; P = .36), and math LD
      (16.1% vs 15.5%; P = .89). CONCLUSIONS: These data from a population-based birth
      cohort indicate that former late preterm infants have similar rates of LD and
      ADHD as term infants.

PMID- 23979093
TI  - Natural history of stuttering to 4 years of age: a prospective community-based
      study.
AB  - OBJECTIVES: To document the natural history of stuttering by age 4 years,
      including (1) cumulative incidence of onset, (2) 12-month recovery status, (3)
      predictors of stuttering onset and recovery, and (4) potential comorbidities. The
      study cohort was a prospective community-ascertained cohort (the Early Language
      in Victoria Study) from Melbourne, Australia, of 4-year-old children (n = 1619;
      recruited at age 8 months) and their mothers. METHODS: Outcome was stuttering
      onset by age 4 years and recovery within 12 months of onset, defined using
      concurrent monthly parent and speech pathologist ratings. Potential predictors:
      child gender, birth weight, birth order, prematurity, and twinning; maternal
      mental health and education; socioeconomic status; and family history of
      stuttering. Potential comorbidities: preonset and concurrent temperament,
      language, nonverbal cognition, and health-related quality of life. RESULTS: By
      age 4 years, the cumulative incidence of stuttering onset was 11.2% (95%
      confidence interval [CI]: 9.7% to 12.8%). Higher maternal education (P = .004),
      male gender (P = .02), and twinning (P = .005) predicted stuttering onset. At
      outcome, stuttering children had stronger language (mean [SD]: 105.0 [13.0] vs
      99.6 [14.6]; mean difference 5.5, 95% CI: 3.1 to 7.8; P < .001) and nonverbal
      cognition (mean [SD]: 106.5 [11.4] vs 103.9 [13.7], mean difference 2.6, 95% CI:
      0.4 to 4.8; P = .02) and better health-related quality of life but were otherwise
      similar to their nonstuttering peers. Only 9 of 142 children (6.3%; 95% CI: 2.9%
      to 11.7%) recovered within 12 months of onset. CONCLUSIONS: Although stuttering
      onset is common in preschoolers, adverse affects are not the norm in the first
      year after onset.

PMID- 23979092
TI  - Interventions to modify health care provider adherence to asthma guidelines: a
      systematic review.
AB  - BACKGROUND AND OBJECTIVE: Health care provider adherence to asthma guidelines is
      poor. The objective of this study was to assess the effect of interventions to
      improve health care providers' adherence to asthma guidelines on health care
      process and clinical outcomes. METHODS: Data sources included Medline, Embase,
      Cochrane CENTRAL Register of Controlled Trials, Cumulative Index to Nursing and
      Allied Health Literature, Educational Resources Information Center, PsycINFO, and
      Research and Development Resource Base in Continuing Medical Education up to July
      2012. Paired investigators independently assessed study eligibility.
      Investigators abstracted data sequentially and independently graded the evidence.
      RESULTS: Sixty-eight eligible studies were classified by intervention: decision
      support, organizational change, feedback and audit, clinical pharmacy support,
      education only, quality improvement/pay-for-performance, multicomponent, and
      information only. Half were randomized trials (n = 35). There was moderate
      evidence for increased prescriptions of controller medications for decision
      support, feedback and audit, and clinical pharmacy support and low-grade evidence
      for organizational change and multicomponent interventions. Moderate evidence
      supports the use of decision support and clinical pharmacy interventions to
      increase provision of patient self-education/asthma action plans. Moderate
      evidence supports use of decision support tools to reduce emergency department
      visits, and low-grade evidence suggests there is no benefit for this outcome with
      organizational change, education only, and quality improvement/pay-for
      performance. CONCLUSIONS: Decision support tools, feedback and audit, and
      clinical pharmacy support were most likely to improve provider adherence to
      asthma guidelines, as measured through health care process outcomes. There is a
      need to evaluate health care provider-targeted interventions with standardized
      outcomes.

PMID- 23979094
TI  - Measuring hospital quality using pediatric readmission and revisit rates.
AB  - OBJECTIVE: To assess variation among hospitals on pediatric readmission and
      revisit rates and to determine the number of high- and low-performing hospitals.
      METHODS: In a retrospective analysis using the State Inpatient and Emergency
      Department Databases from the Healthcare Cost and Utilization Project with
      revisit linkages available, we identified pediatric (ages 1-20 years) visits with
      1 of 7 common inpatient pediatric conditions (asthma, dehydration, pneumonia,
      appendicitis, skin infections, mood disorders, and epilepsy). For each condition,
      we calculated rates of all-cause readmissions and rates of revisits (readmission
      or presentation to the emergency department) within 30 and 60 days of discharge.
      We used mixed logistic models to estimate hospital-level risk-standardized 30-day
      revisit rates and to identify hospitals that had performance statistically
      different from the group mean. RESULTS: Thirty-day readmission rates were low
      (<10.0%) for all conditions. Thirty-day rates of revisit to the inpatient or
      emergency department setting ranged from 6.2% (appendicitis) to 11.0% (mood
      disorders). Study hospitals (n = 958) had low condition-specific visit volumes
      (37.0%-82.8% of hospitals had <25 visits). The only condition with >1% of
      hospitals labeled as different from the mean on 30-day risk-standardized revisit
      rates was mood disorders (4.2% of hospitals [n = 15], range of hospital
      performance 6.3%-15.9%). CONCLUSIONS: We found that when comparing hospitals'
      performances to the average, few hospitals that care for children are identified
      as high- or low-performers for revisits, even for common pediatric diagnoses,
      likely due to low hospital volumes. This limits the usefulness of condition
      specific readmission or revisit measures in pediatric quality measurement.

PMID- 23979095
TI  - Combined bilateral anterior cingulotomy and ventral capsule/ventral striatum deep
      brain stimulation for refractory obsessive-compulsive disorder with major
      depression: do combined procedures have a long-term benefit?
AB  - BACKGROUND: The ventral capsule (VC), ventral striatum (VS), and the anterior
      cingulate gyrus are parts of the obsessive-compulsive disorder (OCD) and
      depression circuits. We assessed whether a combination of bilateral anterior
      cingulotomy and VC/VS deep brain stimulation (DBS) had an additive effect in
      patients with OCD and major depression. METHODS: Three patients with refractory
      OCD underwent combined bilateral anterior cingulotomy and VC/VS DBS procedures.
      All patients met the inclusion criteria for the Korean guidelines of DBS for OCD.
      Baseline Yale-Brown Obsessive-Compulsive Disorder Scale (Y-BOCS) scores, Hamilton
      Depression Rating Scale scores, and global assessments of functioning were
      evaluated. These scores were also serially estimated for more than 24 months
      after surgery at 3-month intervals. RESULTS: The mean value of the baseline Y
      BOCS scores was 34.7 (range 30-38); the mean Y-BOCS value decreased significantly
      to 23.0 (range 20-25) 3 months after the surgery. This score was maintained 2
      years after surgery with a mean value of 19.0 (range 18-20). CONCLUSIONS: The
      combination of the two therapies did not yield superior outcomes, as the clinical
      outcomes were comparable to those of previous reports for VC/VS DBS alone. Wide
      area VC/VS DBS may be sufficient to control refractory OCD.

PMID- 23979096
TI  - Non-work-related personal events contribute to depressive symptoms in Japanese
      discretionary workers.
AB  - In Japan, the number of workers with depressive symptoms has increased recently,
      and long working hours are considered one of the main contributing factors.
      Currently, the number of workers engaging in discretionary work is small but is
      expected to increase, as a diverse method of employment is believed to contribute
      to workers' well-being. However, the factors related to discretionary workers'
      depressive symptoms are unclear. This study aimed to identify the factors
      associated with depressive symptoms in discretionary workers. The subjects were
      240 male discretionary workers in a Japanese insurance company. A cross-sectional
      study was performed using a questionnaire that includes demographic
      characteristics, living and working conditions, work-related and non-work-related
      stressful events, and the Center for Epidemiologic Studies Depression Scale (CES
      D). Depressive symptoms were assessed as more than 16 points on the CES-D.
      Multiple logistic regression models were employed to estimate odd ratios (OR)
      with 95% confidence intervals (95% CI) of depressive symptoms in relation to
      possible factors. Thirty-six subjects (15.5%) showed depressive symptoms. The
      depressive symptoms were significantly related to age (p = 0.04), presence of
      child(ren) (p = 0.02), and length of employment (p = 0.01), but unrelated to
      working hours. Subjects who reported "financial matters" (OR = 4.50, 95% CI =
      1.89-10.72) and "own event" such as divorce or illness (OR = 2.93, 95% CI = 1.13
      7.61) were more likely to show depressive symptoms. In conclusion, mental health
      measures for discretionary workers should focus on addressing financial
      difficulties and consultations and assistance in personal health and family
      issues. 

PMID- 23979097
TI  - Environmental modifications and 2-year measured and self-reported stair-use: a
      worksite randomized trial.
AB  - Environmental modifications have been shown to increase short-term stair use,
      longer-term success is unclear. This study assessed the 2-year effectiveness of
      an environmental intervention promoting worksite stair use. We assessed stair use
      at work by means of self-reports and infrared beam counters (which send a safe
      and invisible beam of infrared light from one side of a stairwell to a reflector
      on the other side; when an individual uses the stairs, the infrared beam is
      disrupted and an instance of stair use is recorded) at six worksites (three
      intervention, three control) in a group randomized, controlled worksite weight
      gain prevention trial in Minneapolis/St. Paul, MN. Intervention modifications
      were signs encouraging stair use, music, and art posters in stairwells. We
      collected data before environmental modifications (2006-2007) and at the end of
      the 2-year intervention (2008-2009). The intervention had a significant positive
      effect on stair use measured both objectively and via self-report, with greatest
      increases reported among those participants who used the stairs least at
      baseline. Following 2-years of continuously-maintained stairwell modifications,
      increases in both objectively-measured and self-reported stair use were
      significantly larger at intervention than control worksites. Study findings
      suggest that the positive impact of environmental modifications on stair use
      persist over a longer time period than has been previously demonstrated. Results
      also indicate that infrequent stair users may be most amenable to the behavior
      changes encouraged by these environmental enhancements. 

PMID- 23979098
TI  - An unusual pathway for the membrane wrapping of rodlike nanoparticles and the
      orientation- and membrane wrapping-dependent nanoparticle interaction.
AB  - Although rapid progress has been made in understanding the interaction of
      nanoparticles (NPs) with lipid membrane, little is known about the interaction
      between neighboring NPs on the membrane. With the aid of computer simulation
      techniques, in this work we systematically investigate the membrane mediated
      interaction between anisotropic NPs with at least one dimension with the size of
      several nanometers, and find that the interaction between neighboring NPs is
      orientation- and membrane wrapping-dependent. For rodlike NPs with a weak NP
      membrane adhesion strength that the membrane wrapping of NPs occurs at a slow
      rate and has a limited extent, the orientation-dependent interaction between two
      neighboring anisotropic NPs arises purely as a result of non-homogeneous
      distribution of membrane curvature induced by anisotropic NP adsorption. While
      for rodlike NPs with a strong NP-membrane adhesion, the rapid wrapping rate and
      extensive wrapping cause the different responses of upper and lower leaflets of
      the membrane to the NP adsorption, which force the NPs to enter the hydrophobic
      part of the membrane and lead to the formation of inverted micelles surrounding
      the NPs. The unusual asymmetrical wrapping also induces orientation-dependent NP
      interaction, which shows a short-range repulsion, intermediate-range attraction
      and long-range repulsion for rodlike NPs. 

PMID- 23979100
TI  - Fear of heights in Roman antiquity and mythology.

PMID- 23979099
TI  - Examining non-locality and quantum coherent dynamics induced by a common
      reservoir.
AB  - If two identical emitters are coupled to a common reservoir, entanglement can be
      generated during the decay process. When using Bell's inequality to examine the
      non-locality, however, it is possible that the bound cannot be violated in some
      cases. Here, we propose to use the steering inequality to examine the non
      locality induced by a common reservoir. Compared with the Bell inequality, we
      find that the steering inequality has a better tolerance for examining non
      locality. In view of the dynamic nature of the entangling process, we also
      propose to observe the quantum coherent dynamics by using the Leggett-Garg
      inequalities. We also suggest a feasible scheme, which consists of two quantum
      dots coupled to nanowire surface plasmons, for possible experimental realization.

PMID- 23979101
TI  - Seroprevalence of anti-N-methyl-D-aspartate receptor antibodies in women with
      ovarian teratoma.
AB  - Recently antibodies against neuronal receptors have been identified as cause of a
      new type of encephalitis. The anti-N-methyl-D-aspartate receptor (anti-NMDA-R)
      encephalitis is the prototype of these disorders. Patients have a high incidence
      of teratomata. Removal of teratoma is considered the essential treatment of anti
      NMDA-R encephalitis. Here, we aimed to investigate whether neurologically
      asymptomatic individuals suffering from ovarian teratomata may have positive anti
      NMDA-R antibodies to be detected by an established assay. Over a time period of
      15 months, all patients suffering from ovarian teratomata without neurological
      symptoms were included in this prospective study. Twenty consecutive patients
      were pair matched to patients with other benign ovarian disease and healthy
      controls. Preoperatively, patients had a gynaecological examination, transvaginal
      ultrasound, neurological examination and determination of anti-NMDA-R antibodies.
      None of the patients or controls presented with neurological symptoms. All
      tumours could be removed completely by laparoscopy. Anti-NMDA-R antibodies were
      absent in the group of patients with teratomata as well as in patients with
      benign ovarian tumours and healthy controls. Testing for anti-NMDA-R antibodies
      revealed negative findings in well-characterised patients with ovarian teratomata
      lacking neurological symptoms. Our data support the current clinical practice
      that a systematic screening for anti-NMDA-R antibodies in teratoma patients is
      not indicated.

PMID- 23979103
TI  - R208H-129VV haplotype in the prion protein gene: phenotype and neuroimaging of a
      patient with genetic Creutzfeldt-Jakob disease.

PMID- 23979104
TI  - Prognostic aspects of DCE-MRI in recurrent rectal cancer.
AB  - OBJECTIVE: To explore whether pre-reoperative dynamic contrast-enhanced (DCE)-MRI
      findings correlate with clinical outcome in patients who undergo surgical
      treatment for recurrent rectal carcinoma. METHODS: A retrospective study of DCE
      MRI in patients with recurrent rectal cancer was performed after obtaining an IRB
      waiver. We queried our PACS from 1998 to 2012 for examinations performed for
      recurrent disease. Two radiologists in consensus outlined tumour regions of
      interest on perfusion images. We explored the correlation between K(trans), Kep,
      Ve, AUC90 and AUC180 with time to re-recurrence of tumour, overall survival and
      resection margin status. Univariate Cox PH models were used for survival, while
      univariate logistic regression was used for margin status. RESULTS: Among 58
      patients with pre-treatment DCE-MRI who underwent resection, 36 went directly to
      surgery and 18 had positive margins. K(trans) (0.55, P = 0.012) and Kep (0.93, P
      = 0.04) were inversely correlated with positive margins. No significant
      correlations were noted between K(trans), Kep, Ve, AUC90 and AUC180 and overall
      survival or time to re-recurrence of tumour. CONCLUSION: K(trans) and Kep were
      significantly associated with clear resection margins; however overall survival
      and time to re-recurrence were not predicted. Such information might be helpful
      for treatment individualisation and deserves further investigation.

PMID- 23979105
TI  - Diffusion tensor imaging of the median nerve in recurrent carpal tunnel syndrome 
      initial experience.
AB  - OBJECTIVES: To investigate median nerve structure in patients with recurrent
      carpal tunnel syndrome (CTS) using diffusion tensor imaging (DTI) and to relate
      DTI changes to anatomical MRI and to measures of median nerve function. METHODS:
      Median nerve structure was quantified according to DTI in patients with recurrent
      CTS and in healthy controls of similar age. Anatomical MRI was used to identify
      the presence of nerve compression and fibrosis. Median nerve function was
      measured using electromyography, a force-tracking task (accuracy of precision
      grip control) and clinical measures. RESULTS: Patients showed reduced apparent
      diffusion coefficient (ADC), reduced axial diffusivity (AD) and radial
      diffusivity (RD) along the median nerve compared with controls (P < 0.001).
      Patients with endoneural fibrosis had the greatest reductions in ADC and in RD.
      ADC and AD correlated positively with nerve conduction velocity (R = 0.54 and R =
      0.68, respectively) and fractional anisotropy correlated negatively with error
      during force-tracking (R = -0.58). CONCLUSIONS: A specific pattern of DTI changes
      in the median nerve was identified in patients with recurrent CTS. Fibrosis may
      be underlying these structural changes. The correlations with nerve conduction
      velocity and accuracy of force control suggest that DTI is a promising technique
      in the study of median nerve structure in recurrent CTS. KEY POINTS: * Diffusion
      tensor imaging (DTI) offers further possibilities in musculoskeletal magnetic
      resonance imaging. * DTI reveals median nerve changes in recurrent carpal tunnel
      syndrome. * DTI changes were greater with signs of median nerve fibrosis. * DTI
      parameters correlated with nerve conduction and force control measures. * DTI is
      a promising technique in recurrent carpal tunnel syndrome.

PMID- 23979106
TI  - MRI-guided vacuum-assisted breast biopsy: comparison with stereotactically guided
      and ultrasound-guided techniques.
AB  - OBJECTIVES: To analyse the development of MRI-guided vacuum-assisted biopsy (VAB)
      in Switzerland and to compare the procedure with stereotactically guided and
      ultrasound-guided VAB. METHODS: We performed a retrospective analysis of VABs
      between 2009 and 2011. A total of 9,113 VABs were performed. Of these, 557 were
      MRI guided. RESULTS: MRI-guided VAB showed the highest growth rate (97 %) of all
      three procedures. The technical success rates for MRI-guided, stereotactically
      guided and ultrasound-guided VAB were 98.4 % (548/557), 99.1 % (5,904/5,960) and
      99.6 % (2,585/2,596), respectively. There were no significant differences (P =
      0.12) between the MRI-guided and the stereotactically guided procedures. The
      technical success rate for ultrasound-guided VAB was significantly higher than
      that for MRI-guided VAB (P < 0.001). There were no complications using MRI-guided
      VAB requiring open surgery. The malignancy diagnosis rate for MRI-guided VAB was
      similar to that for stereotactically guided VAB (P = 0.35). CONCLUSION: MRI
      guided VAB is a safe and accurate procedure that provides insight into clinical
      breast findings. KEY POINTS: * Three vacuum-assisted breast biopsy (VAB)
      procedures were compared. * Technical success rates were high for all three VAB
      procedures. * Medical complications were relatively low using all three VAB
      procedures. * The use of MRI-guided vacuum-assisted breast biopsy is growing.

PMID- 23979107
TI  - 3D mapping of cerebrospinal fluid local volume changes in patients with
      hydrocephalus treated by surgery: preliminary study.
AB  - OBJECTIVE: To develop automated deformation modelling for the assessment of
      cerebrospinal fluid (CSF) local volume changes in patients with hydrocephalus
      treated by surgery. METHODS: Ventricular and subarachnoid CSF volume changes were
      mapped by calculating the Jacobian determinant of the deformation fields obtained
      after non-linear registration of pre- and postoperative images. A total of 31
      consecutive patients, 15 with communicating hydrocephalus (CH) and 16 with non
      communicating hydrocephalus (NCH), were investigated before and after surgery
      using a 3D SPACE (sampling perfection with application optimised contrast using
      different flip-angle evolution) sequence. Two readers assessed CSF volume changes
      using 3D colour-encoded maps. The Evans index and postoperative volume changes of
      the lateral ventricles and sylvian fissures were quantified and statistically
      compared. RESULTS: Before surgery, sylvian fissure and brain ventricle volume
      differed significantly between CH and NCH (P = 0.001 and P = 0.025,
      respectively). After surgery, 3D colour-encoded maps allowed for the visual
      recognition of the CSF volume changes in all patients. The amounts of ventricle
      volume loss of CH and NCH patients were not significantly different (P = 0.30),
      whereas readjustment of the sylvian fissure volume was conflicting in CH and NCH
      patients (P < 0.001). The Evans index correlated with ventricle volume in NCH
      patients. CONCLUSION: 3D mapping of CSF volume changes is feasible providing a
      quantitative follow-up of patients with hydrocephalus. KEY POINTS: * MRI can
      provide helpful information about cerebrospinal fluid volumes. * 3D CSF mapping
      allows quantitative follow-up in communicating and non-communicating
      hydrocephalus. * Following intervention, fissures and cisterns readjust in both
      forms of hydrocephalus. * These findings support the hypothesis of suprasylvian
      block in communicating hydrocephalus. * 3D mapping may improve shunt dysfunction
      detection and guide valve pressure settings.

PMID- 23979108
TI  - Q-elastosonography of solid thyroid nodules: assessment of diagnostic efficacy
      and interobserver variability in a large patient cohort.
AB  - OBJECTIVE: Evaluation of the diagnostic efficacy and interobserver agreement of Q
      elastography in the differentiation of benign from malignant thyroid nodules.
      METHODS: A total of 344 thyroid nodules in 288 patients were examined with grey
      scale and colour Doppler ultrasound (CDUS) and Q-elastography by two independent
      operators. Nodules with hypoechogenicity, poorly defined margins,
      microcalcifications, and intralesional vascularity were classified as suspicious.
      Diagnostic performances of CDUS features and Q-elastography for predicting
      thyroid malignancy were estimated using ROC analysis. Cytology or histopathology
      was the reference standard. Interobserver agreement in the evaluation of CDUS and
      Q-elastography was assessed using Cohen's k-statistic. RESULTS: Q-elastography
      showed excellent diagnostic performance for the prediction of thyroid malignancy,
      with sensitivity of 93 % and specificity of 92 % for operator 1 (best cutoff at
      2.02), and sensitivity of 84 % and specificity of 79 % for operator 2 (best
      cutoff at 1.86). Performance of Q-elastography was superior to that of CDUS.
      Reproducibility of the findings was excellent for both Q-elastography and CDUS
      features as assessed with Cohen's k, which was highest for strain ratio
      measurements (0.95) and lowest for the echogenicity score (0.83). CONCLUSIONS: Q
      elastography showed excellent performance. It is a valid and reproducible
      diagnostic method as well as a promising tool for identifying suspicious solid
      thyroid nodules needing cytological assessment and surgery. KEY POINTS: *
      Elastography is an additional tool for optimal characterisation of malignant
      thyroid nodules. * The use of semiquantitative elastographic evaluation increases
      the diagnostic performance, * The interobserver agreement of quantitative
      elastography can be considered to be good.

PMID- 23979109
TI  - Lead acetate may cause erectile dysfunction by modulating NO/cGMP pathway in rat
      corpus cavernosum.
AB  - Despite the fact that metal toxicity has been widely reported in industrial
      toxicological studies, very little has been reported about the effect of lead
      exposure on erectile function. This study investigated the effect of lead on
      erectile function in rats and aimed to preliminarily test the mechanisms by which
      it might affect erection. Rats were injected with lead acetate (0.25-2 mg/kg)
      intraperitoneally for 21 days. Intracavernosal pressure/mean arterial pressure
      (ICP/MAP) next to nerve stimulation; nitrite/nitrate; malonaldehyde; and reduced
      glutathione levels and superoxide dismutase activity in the corpus cavernosum,
      kidney, and brain were measured in addition to creatinine, urea, and
      testosterone. For acute studies, rats were injected intravenously with lead
      acetate, and then ICP/MAP was recorded for 45 min. Subacute treatment
      significantly reduced erection with significant elevation of malonaldehyde and
      reduction of nitrite/nitrate levels in the corpus cavernosum. In acute studies,
      lead (2 and 5 mg/kg) reduced neurogenic erections by 28.42 +/- 3.76 and 96.84 +/-
      8.52%, respectively, an effect that was masked in the presence of NG-nitro-L
      arginine, tetraethyl ammonium, or methylene blue, but not zinc protoporphyrine,
      and reversed by vitamin C and partially by sildenafil. Lead acetate may inhibit
      the erectile process in rats. Besides its prooxidant effect and consequent
      inactivation of nitric oxide, lead may negatively modulate the action of nitric
      oxide on guanylate cyclase and potassium channels.

PMID- 23979110
TI  - Prognostic indicator for the resection of liver metastasis of colorectal cancer.
AB  - PURPOSE: We investigated the predictive indicator for a good prognosis of
      surgical resection for liver metastasis of colorectal cancer. METHOD: Between
      1990 and 2009 at our institute, 117 patients underwent 132 hepatic resections for
      liver metastasis of colorectal cancer. The clinical, pathological, and outcome
      parameters affecting their prognoses were analyzed. The extent of the liver
      metastases was subdivided according to the Japanese Classification of Colorectal
      Carcinoma (JCCRC), and the patients were classified into different grades based
      on the JCCRC classification and the status of the nodal involvement of the
      primary tumor. RESULT: The median survival time (MST) of the 117 patients was 58
      months, and the actuarial survival rates at 1, 3, and 5 years were 92.3, 60.0,
      and 46.1 %, respectively. A multivariate analysis revealed that the JCCRC Grade
      classification was an independent prognostic indicator (Grade A vs. B vs. C: MST,
      72 vs. 41 vs. 23 months; 5-year survival, 59.0 vs. 38.6 vs. 0 %: p < 0.0001).
      CONCLUSION: Our findings indicate that the JCCRC Grade classification for liver
      metastasis of colorectal cancer is a significant prognostic indicator and may be
      useful for making decisions regarding the treatment of liver metastasis.

PMID- 23979111
TI  - Infants who survive birth at the edge of viability: how are they doing at school
      age?

PMID- 23979112
TI  - Analysis of free fractions for chiral drugs using ultrafast extraction and multi
      dimensional high-performance affinity chromatography.
AB  - A multi-dimensional chromatographic approach was developed to measure the free
      fractions of drug enantiomers in samples that also contained a binding protein or
      serum. This method, which combined ultrafast affinity extraction with a chiral
      stationary phase, was demonstrated using the drug warfarin and the protein human
      serum albumin. 

PMID- 23979113
TI  - Visual Interpretation with Three-Dimensional Annotations (VITA): three
      dimensional image interpretation tool for radiological reporting.
AB  - This paper introduces a software framework called Visual Interpretation with
      Three-Dimensional Annotations (VITA) that is able to automatically generate three
      dimensional (3D) visual summaries based on radiological annotations made during
      routine exam reporting. VITA summaries are in the form of rotating 3D volumes
      where radiological annotations are highlighted to place important clinical
      observations into a 3D context. The rendered volume is produced as a Digital
      Imaging and Communications in Medicine (DICOM) object and is automatically added
      to the study for archival in Picture Archiving and Communication System (PACS).
      In addition, a video summary (e.g., MPEG4) can be generated for sharing with
      patients and for situations where DICOM viewers are not readily available to
      referring physicians. The current version of VITA is compatible with ClearCanvas;
      however, VITA can work with any PACS workstation that has a structured annotation
      implementation (e.g., Extendible Markup Language, Health Level 7, Annotation and
      Image Markup) and is able to seamlessly integrate into the existing reporting
      workflow. In a survey with referring physicians, the vast majority strongly
      agreed that 3D visual summaries improve the communication of the radiologists'
      reports and aid communication with patients. 

PMID- 23979114
TI  - Intracortical bone remodeling variation shows strong genetic effects.
AB  - Intracortical microstructure influences crack propagation and arrest within bone
      cortex. Genetic variation in intracortical remodeling may contribute to
      mechanical integrity and, therefore, fracture risk. Our aim was to determine the
      degree to which normal population-level variation in intracortical microstructure
      is due to genetic variation. We examined right femurs from 101 baboons (74
      females, 27 males; aged 7-33 years) from a single, extended pedigree to determine
      osteon number, osteon area (On.Ar), haversian canal area, osteon population
      density, percent osteonal bone (%On.B), wall thickness (W.Th), and cortical
      porosity (Ct.Po). Through evaluation of the covariance in intracortical
      properties between pairs of relatives, we quantified the contribution of additive
      genetic effects (heritability [h (2)]) to variation in these traits using a
      variance decomposition approach. Significant age and sex effects account for 9 %
      (Ct.Po) to 21 % (W.Th) of intracortical microstructural variation. After
      accounting for age and sex, significant genetic effects are evident for On.Ar (h
      (2) = 0.79, p = 0.002), %On.B (h (2) = 0.82, p = 0.003), and W.Th (h (2) = 0.61,
      p = 0.013), indicating that 61-82 % of the residual variation (after accounting
      for age and sex effects) is due to additive genetic effects. This corresponds to
      48-75 % of the total phenotypic variance. Our results demonstrate that normal,
      population-level variation in cortical microstructure is significantly influenced
      by genes. As a critical mediator of crack behavior in bone cortex, intracortical
      microstructural variation provides another mechanism through which genetic
      variation may affect fracture risk.

PMID- 23979115
TI  - A model of chronic nutrient infusion in the rat.
AB  - Chronic exposure to excessive levels of nutrients is postulated to affect the
      function of several organs and tissues and to contribute to the development of
      the many complications associated with obesity and the metabolic syndrome,
      including type 2 diabetes. To study the mechanisms by which excessive levels of
      glucose and fatty acids affect the pancreatic beta-cell and the secretion of
      insulin, we have established a chronic nutrient infusion model in the rat. The
      procedure consists of catheterizing the right jugular vein and left carotid
      artery under general anesthesia; allowing a 7-day recuperation period; connecting
      the catheters to the pumps using a swivel and counterweight system that enables
      the animal to move freely in the cage; and infusing glucose and/or Intralipid (a
      soybean oil emulsion which generates a mixture of approximately 80%
      unsaturated/20% saturated fatty acids when infused with heparin) for 72 hr. This
      model offers several advantages, including the possibility to finely modulate the
      target levels of circulating glucose and fatty acids; the option to co-infuse
      pharmacological compounds; and the relatively short time frame as opposed to
      dietary models. It can be used to examine the mechanisms of nutrient-induced
      dysfunction in a variety of organs and to test the effectiveness of drugs in this
      context.

PMID- 23979116
TI  - [Use of a portable ultrasound system in the perisurgical assessment of head and
      neck patients].
AB  - PURPOSE: The use of high resolution ultrasound is an established diagnostic
      method. A disadvantage of current high end systems is that transporting the
      device into the operating theatre or an intensive care unit requires time and
      logistic effort. We report results of an evaluation of a portable ultrasound
      system in the diagnosis and treatment of the head and neck area. Indications and
      value of a portable device in the clinical setting of an operation theatre and
      intensive care unit were assessed. METHODS: Within a period of 5 months, 48
      patients were included in this prospectively designed study using a portable
      ultrasound system with B-scan/color Doppler mode (SonoSite TITAN, Firma
      SonoSite(r) Germany) and an 7.5 MHz broadband linear array transducer. Two
      experienced physicians recorded the location and examination conditions, imaging
      mode, time expenditure, indication and diagnosis. The examiner also commented
      about whether the use of a portable laptop system considerably improved the
      therapy decision. The analysis included descriptive statistics for interpretation
      of the results. RESULTS: The most frequent use of the ultrasound system was the
      pre- or intrasurgical "pinpointing" of tumours in the soft tissues of the neck or
      in salivary glands. The average time for the examination was 6 min. In 79 % of
      the cases, the examiner stated a definite improvement of the therapy decision
      through the use of the portable ultrasound. CONCLUSION: We could demonstrate that
      a portable ultrasound system is a time-saving, economic and ubiquitously
      applicable method of imaging. Diagnosis and surgical planning are optimized.
      Thus, in larger hospitals and clinics, a portable ultrasound device is a logical
      complement to a stationary unit.

PMID- 23979117
TI  - [Cardinal symptom vertigo from the neurologist's perspective].
AB  - In most patients with vertigo, the first and clinically most important question
      posed to neurologists is whether it is a central or a peripheral syndrome. In
      more than 90 % of cases, this differentiation is made possible by systematically
      recording the patient history (asking about the type of vertigo, the duration,
      triggers and accompanying symptoms) and conducting a physical examination.
      Particularly in the case of acute vertigo disorders, a five-step procedure has
      proven useful: 1. A cover test to look for vertical divergence (skew deviation)
      as a central sign and component of the ocular tilt reaction (OTR); 2. Examination
      with and without Frenzel goggles to differentiate between peripheral vestibular
      spontaneous nystagmus and central fixation nystagmus; 3. Examination of smooth
      pursuit; 4. Examination of the gaze-holding function (particularly gaze-evoked
      nystagmus beating in the opposite direction to spontaneous nystagmus); 5. The
      head impulse test to look for a deficit in the vestibulo-ocular reflex (VOR).
      Considerable advances have been made in the pharmacotherapy of vertigo disorders
      during the last 10 years, including cortisone for the treatment of acute
      vestibular neuritis, betahistine as a high-dose long-term treatment for Meniere's
      disease, carbamazepine to treat vestibular paroxysmia and aminopyridine for down-
      and upbeat nystagmus and episodic ataxia type 2. 

PMID- 23979118
TI  - Barriers and decisions when answering clinical questions at the point of care: a
      grounded theory study.
AB  - IMPORTANCE: Answering clinical questions affects patient-care decisions and is
      important to continuous professional development. The process of point-of-care
      learning is incompletely understood. OBJECTIVE: To understand what barriers and
      enabling factors influence physician point-of-care learning and what decisions
      physicians face during this process. DESIGN: Focus groups with grounded theory
      analysis. Focus group discussions were transcribed and then analyzed using a
      constant comparative approach to identify barriers, enabling factors, and key
      decisions related to physician information-seeking activities. SETTING: Academic
      medical center and outlying community sites. PARTICIPANTS: Purposive sample of 50
      primary care and subspecialist internal medicine and family medicine physicians,
      interviewed in 11 focus groups. RESULTS: Insufficient time was the main barrier
      to point-of-care learning. Other barriers included the patient comorbidities and
      contexts, the volume of available information, not knowing which resource to
      search, doubt that the search would yield an answer, difficulty remembering
      questions for later study, and inconvenient access to computers. Key decisions
      were whether to search (reasons to search included infrequently seen conditions,
      practice updates, complex questions, and patient education), when to search
      (before, during, or after the clinical encounter), where to search (with the
      patient present or in a separate room), what type of resource to use (colleague
      or computer), what specific resource to use (influenced first by efficiency and
      second by credibility), and when to stop. Participants noted that key features of
      efficiency (completeness, brevity, and searchability) are often in conflict.
      CONCLUSIONS AND RELEVANCE: Physicians perceive that insufficient time is the
      greatest barrier to point-of-care learning, and efficiency is the most important
      determinant in selecting an information source. Designing knowledge resources and
      systems to target key decisions may improve learning and patient care.

PMID- 23979120
TI  - Implant-associated local drug delivery systems based on biodegradable polymers:
      customized designs for different medical applications.
AB  - Implants providing controlled, local release of active substances are of interest
      in different medical applications. Therefore, the focus of the present article is
      the development of implant-associated diffusion- or chemically controlled local
      drug delivery (LDD) systems based on biodegradable polymeric drug carriers. In
      this context, we provide new data and review our own recently published data
      concerning the drug release behavior of diffusion-controlled LDD systems in
      relation to the kind of polymer, drug content, coating mass/thickness, and layer
      composition. We demonstrate that polymers allow a wide range of control over the
      drug release characteristics. In this regard, we show that the glass transition
      temperature of a polymer has an impact on its drug release. Additionally, the
      blending of hydrophobic, semicrystalline polymers with amorphous polymers leads
      to an increase in the rate of drug release compared with the pure semicrystalline
      polymer. Moreover, the percentage loading of the embedded drug has a considerable
      effect on the rate and duration of drug release. Furthermore, we discuss
      chemically controlled LDD systems designed for the release of biomolecules, such
      as growth factors, as well as nanoparticle-mediated LDD systems. With our own
      published data on drug-eluting stents, microstents, and cochlear implants, we
      highlight exemplary implant-associated LDD systems designed to improve implant
      performance through the reduction of undesirable effects such as in-stent
      restenosis and fibrosis.

PMID- 23979119
TI  - Biomarkers for the development of new medications for cocaine dependence.
AB  - There has been significant progress in personalized drug development. In large
      part, this has taken place in the oncology field and been due to the ability of
      researchers/clinicians to discover and develop novel drug development tools
      (DDTs), such as biomarkers. In cancer treatment research, biomarkers have
      permitted a more accurate pathophysiological characterization of an individual
      patient, and have enabled practitioners to target mechanistically the right drug,
      to the right patient, at the right time. Similar to cancer, patients with
      substance use disorders (SUDs) present clinically with heterogeneous
      symptomatology and respond variably to therapeutic interventions. If comparable
      biomarkers could be identified and developed for SUDs, significant diagnostic and
      therapeutic advances could be made. In this review, we highlight current
      opportunities and difficulties pertaining to the identification and development
      of biomarkers for SUDs. We focus on cocaine dependence as an example. Putative
      diagnostic, pharmacodynamic (PD), and predictive biomarkers for cocaine
      dependence are discussed across a range of methodological approaches. A possible
      cocaine-dependent clinical outcome assessment (COA)--another type of defined DDT-
      is also discussed. At present, biomarkers for cocaine dependence are in their
      infancy. Much additional research will be needed to identify, validate, and
      qualify these putative tools prior to their potential use for medications
      development and/or application to clinical practice. However, with a large unmet
      medical need and an estimated market size of several hundred million dollars per
      year, if developed, biomarkers for cocaine dependence will hold tremendous value
      to both industry and public health.

PMID- 23979121
TI  - Poly-4-hydroxybutyrate (P4HB): a new generation of resorbable medical devices for
      tissue repair and regeneration.
AB  - Poly-4-hydroxybutyrate (P4HB) is a thermoplastic, linear polyester, produced by
      recombinant fermentation, that can be converted into a wide range of resorbable
      medical devices. P4HB fibers are exceptionally strong, and can be designed to
      provide prolonged strength retention in vivo. In 2007, the FDA cleared a
      monofilament suture made from P4HB for general soft tissue approximation and/or
      ligation. Subsequently, surgical mesh devices for hernia repair, tendon and
      ligament repair, and plastic and reconstructive surgery have been introduced for
      clinical use. This review describes the unique properties of P4HB, its clinical
      applications, and potential uses that are under development.

PMID- 23979122
TI  - Results of second cochlear implant with long inter-implant delay.
AB  - BACKGROUND: Implantation at a young age enables exposure to language and speech
      during the critical age for language acquisition. Long duration of auditory
      deprivation may lead to less optimal results. METHODS: A retrospective review of
      cases was performed. A young girl with congenital bilateral profound
      sensorineural hearing loss received her first cochlear implant on the right side
      at the age of 21/2 years and successfully developed good speech and language. At
      the age of 10 years, explantation had to be performed, and as reimplantation
      could not be done on the same side, the implantation was done on the left ear,
      which had never received auditory stimulation. Two age-matched girls with
      bilateral sequential implantation, in whom the second sound-deprived ear was
      implanted after a long duration, were studied as well. RESULTS: A year after
      implantation, in two of the cases there was very good speech perception, even in
      noise. In one case, the second ear never attained the ability to understand
      speech. CONCLUSIONS: These results can be explained in light of recent findings
      that early unilateral stimulation can result in bilateral representation in the
      auditory cortex.

PMID- 23979123
TI  - Mutual masking in the cochlea by bone conduction stimulation and by soft tissue
      conduction stimulation in an animal model.
AB  - BACKGROUND: Soft tissue conduction (STC) is a recently described mode of auditory
      stimulation in which vibrations induced by a clinical bone vibrator applied to
      soft tissue sites on the head, neck, and thorax of human subjects reach the
      cochlea and elicit auditory sensation. In humans, STC stimulation interacts with
      air conduction stimulation and with bone conduction (BC) stimulation in several
      ways, e.g., mutual masking. METHODS: This study investigated whether mutual
      masking between STC and BC stimulation can be demonstrated in an experimental
      animal. In fat sand rats, auditory nerve and brainstem evoked response to BC
      stimulation was recorded in the presence of noise masking presented by STC and
      vice versa. RESULTS: STC successfully masked BC, and BC also masked STC
      responses. CONCLUSIONS: Mutual masking, now demonstrated in animals, paves the
      way for animal experiments to clarify the pathway between the STC stimulation
      sites and the cochlea.

PMID- 23979124
TI  - Longitudinal evaluation of thyroid autoimmunity and function in pregnant Korean
      women.
AB  - BACKGROUND: Maternal thyroid dysfunction during pregnancy has been associated
      with adverse outcomes for both the mother and child. For this reason, it is
      important to understand thyroid status in pregnant women. However, there are
      relatively few published studies that examine thyroid function tests (TFT) and
      thyroid autoimmunity in non-Western pregnant women. METHODS: Serum samples were
      longitudinally collected throughout pregnancy from 108 Korean women. TFT, thyroid
      peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) testing was
      performed. The impact of gestational age on TPO-Ab and Tg-Ab levels was evaluated
      and gestational age-specific reference intervals for TFT were established in
      antibody negative women. RESULTS: In the first trimester, TPO-Ab and Tg-Ab were
      positive in 13.9% and 16.7% of women, respectively. For antibody positive women,
      median autoantibody levels for TPO-Ab and Tg-Ab dropped from first trimester to
      near term (133.7-10.5 IU/mL, and 162.1-21.9 IU/mL, respectively). Antibody status
      influenced thyroid stimulating hormone (TSH) during the first trimester, and TSH,
      free T4 (FT4) and total T4 (TT4) in the early second trimester. Later in
      gestation, no significant differences in TFT were found based on antibody status.
      Gestational age-specific reference intervals for TFT were calculated in antibody
      negative women. CONCLUSIONS: Laboratory evidence of autoimmune thyroid disease
      (AITD) is common in this population of pregnant Korean women. Antibody status
      influences TFT values in the first and early second trimester. Thyroid
      autoantibody status and titer change in an individual-specific manner throughout
      pregnancy. Gestational age-specific reference intervals should be utilized for
      interpretation of TFT results in pregnant women.

PMID- 23979125
TI  - Formation of nitri- and nitrosylhemoglobin in systems modeling the Maillard
      reaction.
AB  - BACKGROUND: Nitric oxide (NO) and its metabolites can nitrosylate hemoglobin (Hb)
      through the heme iron. Nitrihemoglobin (nitriHb) can be formed as result of
      porphyrin vinyl group modification with nitrite. However, in those with diabetes
      the non-enzymatic glycation of Hb amino acids residues (the Maillard reaction)
      can take place. The objectives of this study were to investigate effects of the
      Maillard reaction on the interaction of methemoglobin (metHb) with S
      nitrosoglutathione (GSNO) and nitrite. METHODS: Nitrosylhemoglobin production was
      registered using increasing optical density at 572 nm and compared with 592 nm,
      and with EPR spectroscopy. Formation of nitriHb was determined using an
      absorbance band of reduced hemochromogen (582 nm) in the alkaline pyridine
      solution. Accumulation of fluorescent advanced glycation end-products of Hb was
      measured through increasing of fluorescence at 385-395 nm (excitation lambda=320
      nm). RESULTS: We determined that NO metabolites such as GSNO and nitrite at
      physiological pH values and aerobic conditions caused modification of metHb
      porphyrin vinyl groups with nitriHb formation. It was ascertained that this
      formation was inhibited by superoxide dismutase. In microaerobic conditions metHb
      was nitrosylated under the action of GSNO or GSNO with methylglyoxal. Nitrite
      nitrosylated metHb only in the presence of methylglyoxal. It was shown that GSNO
      inhibited accumulation of fluorescent products which formed during Hb glycation
      with methylglyoxal. CONCLUSIONS: The assumption was made that intermediates of
      the Hb glycation reaction play an important role both in vinyl group nitration
      and in heme iron nitrosylation. Oxygen content in reaction medium is an important
      factor influencing these processes. These effects can play an important role in
      pathogenesis of the diseases connected with carbonyl, oxidative and nitrosative
      stresses.

PMID- 23979126
TI  - Digital immunofluorescence enables automated detection of antinuclear antibody
      endpoint titers avoiding serial dilution.

PMID- 23979127
TI  - Increased B-type natriuretic peptide levels in early-onset versus late-onset
      preeclampsia.
AB  - BACKGROUND: We compared B-type natriuretic peptide (BNP) levels, clinical and
      laboratory findings in early-onset preeclampsia (EOP), late-onset preeclampsia
      (LOP) and healthy pregnant groups. METHODS: We studied 40 healthy pregnant and 40
      preeclamptic patients. Preeclamptics were divided in two groups, the EOP group
      (n=20) and LOP group (n=20), according to gestational age at the onset of
      disease. The distinction criterion for early- vs. late-onset was set as week 34
      of gestation. The concentration of the BNP levels was measured by a sandwich
      fluorescence immunoassay. For statistical analysis of the clinical and laboratory
      findings non-parametric methods were applied. RESULTS: BNP levels were higher in
      EOP [61.35 (36.95-93.25) pg/mL] and LOP patients [32.4 (19.15-39.2) pg/mL] than
      in healthy pregnant women [10.05 (6.08-16.03) pg/mL] (both p<0.001). Furthermore,
      EOPs had significantly higher BNP levels as compared to LOP patients (p<0.001). A
      BNP cut-off <24.5 pg/mL had a negative-predictive value of 85.1% excluding
      preeclampsia. There was a significant inverse correlation between plasma BNP
      levels of EOP patients and sodium (p<0.05) and total protein concentrations
      (p<0.05). In the EOP group, a significant positive correlation was observed
      between plasma levels of BNP and hematocrit (p<0.05), serum potassium (p<0.05),
      urea (p<0.05) and 24-h proteinuria (p<0.05). CONCLUSIONS: BNP levels were
      significantly higher in EOP than in LOP patients. The cut-off value <24.5 pg/mL
      seems to be a powerful discriminative indicator excluding preeclampsia. The
      amount of proteinuria and total protein levels correlate with the elevation of
      the BNP levels. In EOP the extent of proteinuria is higher than in the LOP.

PMID- 23979128
TI  - Letter to the editor.

PMID- 23979129
TI  - Response from the author.

PMID- 23979130
TI  - HOXA-11 mediated dysregulation of matrix remodeling during implantation window in
      women with endometriosis.
AB  - PURPOSE: To investigate the Homeobox genes HOXA-10 and HOXA-11 mediated
      endometrial molecular defects during implantation window in endometriosis
      associated infertility cases. METHODS: Endometrial biopsies were obtained during
      implantation window from 31 infertile women with endometriosis (age < 35 years)
      and 26 age and BMI-matched infertile women without endometriosis were included in
      the study for comparison purposes. Endometrial expression of HOXA-10 and HOXA-11
      genes, MMP-2, -9, alpha(v)beta(3) integrin, leukemia inhibitory factor and
      surface characteristics including average roughness and topology were assessed.
      RESULTS: A significantly lower expression of HOXA-10 and HOXA-11 were observed in
      endometriotic women compared to non-endometriotic controls. Further, a
      significantly higher endometrial expression of MMP-2 and -9 were observed in
      women with endometriosis when compared with controls. Interestingly, endometrial
      surface were observed to be grossly affected in terms of average roughness and
      topology in women with endometriosis compared to controls. CONCLUSIONS: The
      findings suggest that aberrant expression of HOXA-10 and -11 genes adversely
      affects endometrial remodelling and expression of receptivity markers.

PMID- 23979131
TI  - More than just a cargo adapter, melanophilin prolongs and slows processive runs
      of myosin Va.
AB  - Myosin Va (myoVa) is a molecular motor that processively transports cargo along
      actin tracks. One well studied cargo in vivo is the melanosome, a pigment
      organelle that is moved first by kinesin on microtubules and then handed off to
      myoVa for transport in the actin-rich dendritic periphery of melanocytes.
      Melanophilin (Mlph) is the adapter protein that links Rab27a-melanosomes to
      myoVa. Using total internal reflection fluorescence microscopy and quantum dot
      labeled full-length myoVa, we show at the single-molecule level that Mlph
      increases the number of processively moving myoVa motors by 17-fold.
      Surprisingly, myoVa-Mlph moves ~4-fold slower than myoVa alone and with twice the
      run length. These two changes greatly increase the time spent on actin, a
      property likely to enhance the transfer of melanosomes to the adjacent
      keratinocyte. In contrast to the variable stepping pattern of full-length myoVa,
      the myoVa-Mlph complex shows a normal gating pattern between the heads typical of
      a fully active motor and consistent with a cargo-dependent activation mechanism.
      The Mlph-dependent changes in myoVa depend on a positively charged cluster of
      amino acids in the actin binding domain of Mlph, suggesting that Mlph acts as a
      "tether" that links the motor to the track. Our results provide a molecular
      explanation for the uncharacteristically slow speed of melanosome movement by
      myoVa in vivo. More generally, these data show that proteins that link motors to
      cargo can modify motor properties to enhance their biological role.

PMID- 23979132
TI  - Oxidized low density lipoprotein (LDL) affects hyaluronan synthesis in human
      aortic smooth muscle cells.
AB  - Thickening of the vessel in response to high low density lipoprotein(s) (LDL)
      levels is a hallmark of atherosclerosis, characterized by increased hyaluronan
      (HA) deposition in the neointima. Human native LDL trapped within the arterial
      wall undergoes modifications such as oxidation (oxLDL). The aim of our study is
      to elucidate the link between internalization of oxLDL and HA production in
      vitro, using human aortic smooth muscle cells. LDL were used at an effective
      protein concentration of 20-50 MUg/ml, which allowed 80% cell viability. HA
      content in the medium of untreated cells was 28.9 +/- 3.7 nmol HA
      disaccharide/cell and increased after oxLDL treatment to 53.9 +/- 5.6. OxLDL
      treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA
      stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to
      extracellular matrix. The effects induced by oxLDL were inhibited by blocking LOX
      1 scavenger receptor with a specific antibody (10 MUg/ml). The cholesterol moiety
      of LDL has an important role in HA accumulation because cholesterol-free oxLDL
      failed to induce HA synthesis. Nevertheless, cholesterol-free oxLDL and
      unmodified cholesterol (20 MUg/ml) induce only HAS3 transcription, whereas
      22,oxysterol affects both HAS2 and HAS3. Moreover, HA deposition was associated
      with higher expression of endoplasmic reticulum stress markers (CHOP and GRP78).
      Our data suggest that HA synthesis can be induced in response to specific
      oxidized sterol-related species delivered through oxLDL. 

PMID- 23979134
TI  - MicroRNA-433 inhibits liver cancer cell migration by repressing the protein
      expression and function of cAMP response element-binding protein.
AB  - We show for the first time that potent microRNA-433 (miR-433) inhibition of
      expression of the cAMP response element-binding protein CREB1 represses
      hepatocellular carcinoma (HCC) cell migration. We identified a miR-433 seed match
      region in human and mouse CREB1 3'-UTRs. Overexpression of miR-433 markedly
      decreased human CREB1 3'-UTR reporter activity, and the inhibitory effect of miR
      433 was alleviated upon mutation of its binding site. Ectopic expression of miR
      433 reduced CREB1 protein levels in a variety of human and mouse cancer cells,
      including HeLa, Hepa1, Huh7, and HepG2. Human CREB1 protein levels in highly
      invasive MHCC97H cells were diminished by expression of miR-433 but were induced
      by miR-433 antagomir (anti-miR-433). The expression of mouse CREB1 protein
      negatively correlated with miR-433 levels in nuclear receptor Shp(-/-) liver
      tissues and liver tumors compared with wild-type mice. miR-433 exhibited a
      significant repression of MHCC97H cell migration, which was reversed by anti-miR
      433. Overexpressing miR-433 inhibited focus formation dramatically, demonstrating
      that miR-433 may exert a tumor suppressor function. Knockdown of CREB1 by siRNAs
      impeded MHCC97H cell migration and invasion and antagonized the effect of anti
      miR-433. Interestingly, CREB1 siRNA decreased MHCC97H cell proliferation, which
      was not influenced by anti-miR-433. Overexpressing CREB1 decreased the inhibitory
      activity of miR-433. The CpG islands surrounding miR-433 were hypermethylated,
      and the DNA methylation agent 5'-aza-2'-deoxycytidine, but not the histone
      deacetylase inhibitor trichostatin A, drastically stimulated the expression of
      miR-433 and miR-127 in HCC cells. The latter is clustered with miR-433. The
      results reveal a critical role of miR-433 in mediating HCC cell migration via
      CREB1. 

PMID- 23979133
TI  - Llama-derived single variable domains (nanobodies) directed against chemokine
      receptor CXCR7 reduce head and neck cancer cell growth in vivo.
AB  - The chemokine receptor CXCR7, belonging to the membrane-bound G protein-coupled
      receptor superfamily, is expressed in several tumor types. Inhibition of CXCR7
      with either small molecules or small interference (si)RNA has shown promising
      therapeutic benefits in several tumor models. With the increased interest and
      effectiveness of biologicals inhibiting membrane-bound receptors we made use of
      the "Nanobody platform" to target CXCR7. Previously we showed that Nanobodies,
      i.e. immunoglobulin single variable domains derived from naturally occurring
      heavy chain-only camelids antibodies, represent new biological tools to
      efficiently tackle difficult drug targets such as G protein-coupled receptors. In
      this study we developed and characterized highly selective and potent Nanobodies
      against CXCR7. Interestingly, the CXCR7-targeting Nanobodies displayed
      antagonistic properties in contrast with previously reported CXCR7-targeting
      agents. Several high affinity CXCR7-specific Nanobodies potently inhibited CXCL12
      induced beta-arrestin2 recruitment in vitro. A wide variety of tumor biopsies was
      profiled, showing for the first time high expression of CXCR7 in head and neck
      cancer. Using a patient-derived CXCR7-expressing head and neck cancer xenograft
      model in nude mice, tumor growth was inhibited by CXCR7-targeting Nanobody
      therapy. Mechanistically, CXCR7-targeting Nanobodies did not inhibit cell cycle
      progression but instead reduced secretion of the angiogenic chemokine CXCL1 from
      head and neck cancer cells in vitro, thus acting here as inverse agonists, and
      subsequent angiogenesis in vivo. Hence, with this novel class of CXCR7
      inhibitors, we further substantiate the therapeutic relevance of targeting CXCR7
      in head and neck cancer. 

PMID- 23979135
TI  - Fibroblast growth factor signaling is essential for self-renewal of dental
      epithelial stem cells.
AB  - A constant supply of epithelial cells from dental epithelial stem cell (DESC)
      niches in the cervical loop (CL) enables mouse incisors to grow continuously
      throughout life. Elucidation of the cellular and molecular mechanisms underlying
      this unlimited growth potential is of broad interest for tooth regenerative
      therapies. Fibroblast growth factor (FGF) signaling is essential for the
      development of mouse incisors and for maintenance of the CL during prenatal
      development. However, how FGF signaling in DESCs controls the self-renewal and
      differentiation of the cells is not well understood. Herein, we report that FGF
      signaling is essential for self-renewal and the prevention of cell
      differentiation of DESCs in the CL as well as in DESC spheres. Inhibiting the FGF
      signaling pathway decreased proliferation and increased apoptosis of the cells in
      DESC spheres. Suppressing FGFR or its downstream signal transduction pathways
      diminished Lgr5-expressing cells in the CL and promoted cell differentiation both
      in DESC spheres and the CL. Furthermore, disruption of the FGF pathway abrogated
      Wnt signaling to promote Lgr5 expression in DESCs both in vitro and in vivo. This
      study sheds new light on understanding the mechanism by which the homeostasis,
      expansion, and differentiation of DESCs are regulated. 

PMID- 23979136
TI  - Structural insights into the unusually strong ATPase activity of the AAA domain
      of the Caenorhabditis elegans fidgetin-like 1 (FIGL-1) protein.
AB  - The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose
      mutation leads to multiple developmental defects. The FIGL-1 protein contains an
      AAA (ATPase associated with various activities) domain and belongs to the AAA
      superfamily. However, the biological functions and developmental implications of
      this protein remain unknown. Here, we show that the AAA domain of the
      Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to
      homologous AAA domains, has an unusually high ATPase activity and forms a hexamer
      in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that
      the loop linking helices alpha9 and alpha10 folds into the short helix alpha9a,
      which has an acidic surface and interacts with a positively charged surface of
      the neighboring subunit. Disruption of this charge interaction by mutagenesis
      diminishes both the ATPase activity and oligomerization capacity of the protein.
      Interestingly, the acidic residues in helix alpha9a of CeFIGL-1-AAA are not
      conserved in other homologous AAA domains that have relatively low ATPase
      activities. These results demonstrate that the sequence of CeFIGL-1-AAA has
      adapted to establish an intersubunit charge interaction, which contributes to its
      strong oligomerization and ATPase activity. These unique properties of CeFIGL-1
      AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may
      have a distinct biological function. 

PMID- 23979137
TI  - Guanine nucleotide exchange factors (GEFs) have a critical but not exclusive role
      in organelle localization of Rab GTPases.
AB  - Membrane fusion at eukaryotic organelles is initiated by Rab GTPases and
      tethering factors. Rabs in their GDP-bound form are kept soluble in the cytoplasm
      by the GDP dissociation inhibitor (GDI) chaperone. Guanine nucleotide exchange
      factors (GEFs) are found at organelles and are critical for Rab function. Here,
      we surveyed the overall role of GEFs in Rab localization. We show that GEFs, but
      none of the proposed GDI displacement factors, are essential for the correct
      membrane localization of yeast Rabs. In the absence of the GEF, Rabs lost their
      primary localization to the target organelle. Several Rabs, such as vacuolar
      Ypt7, were found at the endoplasmic reticulum and thus were still membrane-bound.
      Surprisingly, a Ypt7 mutant that undergoes facilitated nucleotide exchange
      localized to vacuoles independently of its GEF Mon1-Ccz1 and rescued vacuole
      morphology. In contrast, wild-type Ypt7 required its GEF for localization and to
      counteract the extraction by GDI. Our data agree with the emerging model that
      GEFs are critical for Rab localization but raise the possibility that additional
      factors can contribute to this process. 

PMID- 23979138
TI  - Dynamic regulation of Ero1alpha and peroxiredoxin 4 localization in the secretory
      pathway.
AB  - In the early secretory compartment (ESC), a network of chaperones and enzymes
      assists oxidative folding of nascent proteins. Ero1 flavoproteins oxidize protein
      disulfide isomerase (PDI), generating H2O2 as a byproduct. Peroxiredoxin 4 (Prx4)
      can utilize luminal H2O2 to oxidize PDI, thus favoring oxidative folding while
      limiting oxidative stress. Interestingly, neither ER oxidase contains known ER
      retention signal(s), raising the question of how cells prevent their secretion.
      Here we show that the two proteins share similar intracellular localization
      mechanisms. Their secretion is prevented by sequential interactions with PDI and
      ERp44, two resident proteins of the ESC-bearing KDEL-like motifs. PDI binds
      preferentially Ero1alpha, whereas ERp44 equally retains Ero1alpha and Prx4. The
      different binding properties of Ero1alpha and Prx4 increase the robustness of ER
      redox homeostasis. 

PMID- 23979139
TI  - Physicochemical factors controlling the activity and energy coupling of an ionic
      strength-gated ATP-binding cassette (ABC) transporter.
AB  - Cells control their volume through the accumulation of compatible solutes. The
      bacterial ATP-binding cassette transporter OpuA couples compatible solute uptake
      to ATP hydrolysis. Here, we study the gating mechanism and energy coupling of
      OpuA reconstituted in lipid nanodiscs. We show that anionic lipids are essential
      both for the gating and the energy coupling. The tight coupling between substrate
      binding on extracellular domains and ATP hydrolysis by cytoplasmic nucleotide
      binding domains allows the study of transmembrane signaling in nanodiscs. From
      the tight coupling between processes at opposite sides of the membrane, we infer
      that the ATPase activity of OpuA in nanodiscs reflects solute translocation.
      Intriguingly, the substrate-dependent, ionic strength-gated ATPase activity of
      OpuA in nanodiscs is at least an order of magnitude higher than in lipid vesicles
      (i.e. with identical membrane lipid composition, ionic strength, and nucleotide
      and substrate concentrations). Even with the chemical components the same, the
      lateral pressure (profile) of the nanodiscs will differ from that of the
      vesicles. We thus propose that membrane tension limits translocation in vesicular
      systems. Increased macromolecular crowding does not activate OpuA but acts
      synergistically with ionic strength, presumably by favoring gating interactions
      of like-charged surfaces via excluded volume effects. 

PMID- 23979141
TI  - The influence of two cognitive-linguistic variables on incidental word learning
      in 5-year-olds.
AB  - The relation between incidental word learning and two cognitive-linguistic
      variables--phonological memory and phonological awareness--is not fully
      understood. Thirty-five typically developing, 5-year-old, preschool children
      participated in a study examining the association between phonological memory,
      phonological awareness, and incidental word learning. Children were exposed to
      target words in a read-aloud story that accompanied a wordless picture book.
      Target word comprehension was assessed before and after two readings of the
      story. Phonological awareness predicted incidental word learning but phonological
      memory did not. The influence of phonological awareness and phonological memory
      on word learning may be dependent on the demands of the word learning task.

PMID- 23979140
TI  - Regulated norepinephrine transporter interaction with the neurokinin-1 receptor
      establishes transporter subcellular localization.
AB  - Neurokinin-1 receptor (NK1R) mediates down-regulation of human norepinephrine
      (NE) transporter (hNET) via protein kinase C (PKC). However, native NET
      regulation by NK1R and the mechanism by which NK1R targets NET among other
      potential effectors are unknown. Effect of NK1R activation on native NET
      regulation and NET/NK1R interaction were studied using rat brain synaptosomes
      expressing native NET and NK1R as well as human placental trophoblast (HTR) cells
      coexpressing WT-hNET or NK1R/PKC-resistant hNET-T258A,S259A double mutant (NET
      DM) and hNK1R. The selective NK1R agonist, GR73632, and Substance-P (SP)
      inhibited NE transport and reduced plasma membrane expression of NET and NK1R.
      Pretreatment with the NK1R antagonist, EMEND (aprepitant) prevented these NK1R
      mediated effects. Immunoprecipitation experiments showed that NET forms stable
      complexes with NK1R. In HTR cells, combined biotinylation and immunoprecipitation
      studies revealed plasma membrane localization of NET.NK1R complexes. Receptor
      activation resulted in the internalization of NET.NK1R complexes. Lipid raft and
      immunoprecipitation analyses revealed the presence of NET.NK1R complexes
      exclusively in non-raft membrane fractions under basal/unstimulated conditions.
      However, NK1R activation led to translocation of NET.NK1R complexes to raft-rich
      membrane fractions. Importantly, PKCalpha was found in association with raft
      localized NET following SP treatment. Similar to WT-NET, PKC-resistant NET-DM was
      found in association with NK1R exclusively in non-raft fractions. However, SP
      treatment failed to translocate NET-DM.NK1R complexes from non-raft fractions to
      raft fractions. Collectively, these results suggest that NK1R forms physical
      complexes with NET and that the receptor-mediated Thr(258) + Ser(259) motif
      dependent translocation of NET.NK1R complexes into raft-rich microdomains
      facilitates NET/NK1R interaction with PKCalpha to coordinate spatially restricted
      NET regulation. 

PMID- 23979142
TI  - Substrate-mediated charge transfer plasmons in simple and complex nanoparticle
      clusters.
AB  - A conductive substrate can provide a simple and straightforward way to induce
      charge-transfer plasmon modes in Au nanoparticle clusters. For a simple dimer
      structure, a remarkably narrow charge transfer plasmon, which differs
      dramatically from the dipolar plasmon mode of the electrically isolated
      nanostructure, is clearly observed. For a more complex nonamer cluster that
      supports a strong Fano resonance on an insulating substrate, a mixed charge
      transfer-dipole mode is observed, where charge transfer is induced on the outer
      nanoparticles, establishing an opposing dipole on the intervening central
      particles, resulting in a strongly damped far field response. 

PMID- 23979143
TI  - Can drug interactions be evaluated by monitoring plasma drug concentrations?

PMID- 23979145
TI  - Exposure to respirable dust and manganese and prevalence of airways symptoms,
      among Swedish mild steel welders in the manufacturing industry.
AB  - PURPOSE: Welding fume consists of metal fumes, e.g., manganese (Mn) and gases,
      e.g., ozone. Particles in the respirable dust (RD) size range dominate. Exposure
      to welding fume could cause short- and long-term respiratory effects. The
      prevalence of work-related symptoms among mild steel welders was studied, and the
      occupational exposure to welding fumes was quantified by repeated measurements of
      RD, respirable Mn, and ozone. Also the variance components were studied. METHOD:
      A questionnaire concerning airway symptoms and occupational history was answered
      by 79% of a cohort of 484 welders. A group of welders (N = 108) were selected and
      surveyed by personal exposure measurements of RD and ozone three times during 1
      year. RESULTS: The welders had a high frequency of work-related symptoms, e.g.,
      stuffy nose (33%), ocular symptoms (28%), and dry cough (24%). The geometric mean
      exposure to RD and respirable Mn was 1.3 mg/m(3) (min-max 0.1-38.3 mg/m(3)) and
      0.08 mg/m(3) (min-max <0.01-2.13 mg/m(3)), respectively. More than 50% of the Mn
      concentrations exceeded the Swedish occupational exposure limit (OEL). Mainly,
      low concentrations of ozone were measured, but 2% of the samples exceeded the
      OEL. Of the total variance for RD, 30 and 33% can be attributed to within-worker
      variability and between-company variability, respectively. CONCLUSIONS: Welders
      had a high prevalence of work-related symptom from the airways and eyes. The
      welders' exposure to Mn was unacceptably high. To reduce the exposure further,
      control measures in the welding workshops are needed. Correct use of general
      mechanical ventilation and local exhaust ventilation can, for example,
      efficiently reduce the exposure.

PMID- 23979146
TI  - Medical risks in older pilots: a systematic review on incapacitation and age.
AB  - PURPOSE: Our ageing society faces an ageing work force. The target of this
      systematic review was to analyse whether pilots have a measurable age-dependent
      increased risk of incapacitation due to medical reasons. METHODS: Publications
      listed in PubMed, NCBI and EMBASE were identified using defined terms. Two
      independent raters analysed 2,342 retrieved publications by predefined criteria.
      Ten publications met the inclusion criteria. RESULTS: Four publications use a
      similar numerator (in-flight incapacitation) and identical denominator (flight
      hours) and show in-flight incapacitation of pilots happening 0.19-0.45
      times/10(6) flight hours. Two of these studies did not analyse the possible
      correlation of incapacitation and age, and two did not use the denominator flight
      hours here. Age dependency of incapacitation is analysed in seven publications:
      Three analyse in-flight incapacitation and four analyse general incapacitation to
      fly. All but one--the only one including professional pilots older than 60 years-
      show an age-depending increase in incapacitation. The increase in in-flight
      incapacitation is far less than the increase in general flight incapacitation.
      CONCLUSIONS: Medical in-flight incapacitation is a very rare event. Whether the
      increase in in-flight incapacitation results in an increase in accidents or can
      be compensated for by error reduction through experience cannot be answered. A
      register of all pilots with a clear identification system to follow their career
      and health, their accidents and impairments, might help to reconsider the
      grounding of pilots over 60 and to define better criteria than mere age.

PMID- 23979147
TI  - A review of mercury exposure among artisanal small-scale gold miners in
      developing countries.
AB  - PURPOSE: Extraction of gold using mercury has been a way out of poverty for
      millions of people in developing countries. Artisanal small-scale gold mining
      (ASGM) has expanded during the last decades and is often carried out under
      primitive conditions. Thus, workers in this industry may be exposed to high
      levels of mercury and suffer from toxic effects from mercury exposure. The
      objective of this review was to provide an outline of the studies available on
      elemental mercury exposure among artisanal small-scale gold miners. METHODS:
      Searching the PubMed and Embase databases, 26 studies with a total of 3,005
      exposed subjects and 442 controls across 14 different developing countries were
      found. Urine mercury levels were used as biomarkers of exposure. RESULTS: In
      general, the urine mercury levels were elevated and a considerable proportion of
      workers had urine mercury levels above existing guidelines. Exposed subjects were
      stratified into residents, miners, millers, smelters, and refiners, who by work
      task content were expected to be increasingly exposed to mercury. This group
      order did show a clear trend of increasing mercury levels. Mercury levels
      differed substantially between studies. Possible explanations include
      dissimilarities in gold extraction methods, use of protective devices, and
      selection of participants. CONCLUSIONS: This review provides evidence that
      artisanal gold miners and residents of the mining sites are exposed to mercury
      vapour to an extent where acute and long-term toxic effects of mercury are
      likely. Interventions aimed at reducing exposure and emission of mercury from
      ASGM are needed.

PMID- 23979148
TI  - The Integral Theory System Questionnaire: an anatomically directed questionnaire
      to determine pelvic floor dysfunctions in women.
AB  - PURPOSE: Anatomical damage to pelvic floor structures may cause multiple
      symptoms. The Integral Theory System Questionnaire (ITSQ) is a holistic
      questionnaire that uses symptoms to help locate damage in specific connective
      tissue structures as a guide to reconstructive surgery. It is based on the
      integral theory, which states that pelvic floor symptoms and prolapse are both
      caused by lax suspensory ligaments. The aim of the present study was to
      psychometrically validate the ITSQ. MATERIALS AND METHODS: Established
      psychometric properties including validity, reliability, and responsiveness were
      considered for evaluation. Criterion validity was assessed in a cohort of 110
      women with pelvic floor dysfunctions by analyzing the correlation of
      questionnaire responses with objective clinical data. Test-retest was performed
      with questionnaires from 47 patients. Cronbach's alpha and "split-half"
      reliability coefficients were calculated for inner consistency analysis. RESULTS:
      Psychometric properties of ITSQ were comparable to the ones of previously
      validated Pelvic Floor Questionnaires. Face validity and content validity were
      approved by an expert group of the International Collaboration of Pelvic Floor
      surgeons. Convergent validity assessed using Bayesian method was at least as
      accurate as the expert assessment of anatomical defects. Objective data
      measurement in patients demonstrated significant correlations with ITSQ domains
      fulfilling criterion validity. Internal consistency values ranked from 0.85 to
      0.89 in different scenarios. CONCLUSIONS: The ITSQ proofed accurate and is able
      to serve as a holistic Pelvic Floor Questionnaire directing symptoms to site
      specific pelvic floor reconstructive surgery.

PMID- 23979149
TI  - New ex vivo organ model for percutaneous renal surgery using a laparoendoscopic
      training box: the sandwich model.
AB  - PURPOSE: Percutaneous renal surgery (PRS) is a challenging procedure for urologic
      surgeons and requires a large variety of different skills. Our objective was to
      improve the preexisting porcine kidney-training model for percutaneous renal
      access and PRS. METHODS: For our biologic training model, we use porcine kidneys
      with preserved ureter. The ureter was dissected, stones were placed into the
      collecting system using a 16, 5F Amplatz sheath, and a 12Ch indwelling catheter
      was placed in the ureter for further irrigation with blue-dyed saline. The kidney
      was placed between two porcine full-thickness skin lobes in an existing
      laparoscopy trainer (SITUS Box). The kidney was punctured with ultrasound
      guidance, and minimally invasive percutaneous nephrolithotomy (MIP) was then
      performed as previously described. The model was evaluated in MIP training
      courses, which are regularly held at the Hannover Medical School. RESULTS: All
      trainees were urologists with experience in endourologic surgery. Eleven
      participants were trained in this model. Percutaneous puncture under
      ultrasonographic guidance and following intrarenal surgery was successful in all
      11 (100 %) cases. Therefore, all participants rated the model useful for
      simulating percutaneous renal surgery. CONCLUSION: Compared to recently published
      models, this new porcine kidney model is easy to prepare and is cost-effective by
      using standard material. Moreover, it provides realistic and reproducible
      practice for PRS in the laboratory. Unfavorably, the described organ model
      requires an existing laparoscopy training system. Comprehensively, the presented
      organ model approximates the natural retroperitoneal circumstances precisely by
      using the two full-thickness skin flaps with the fatty subcutaneous tissue.

PMID- 23979150
TI  - Holmium:YAG laser ureteroscopic lithotripsy for ureteric calculi in children:
      predictive factors for complications and success.
AB  - OBJECTIVES: To evaluate the impact of age, stone size, location, radiolucency,
      extraction of stone fragments, size of ureteroscope and presence and degree of
      hydronephrosis on the efficacy and safety of holmium:YAG (Ho:YAG) laser
      lithotripsy in the ureteroscopic treatment of ureteral stones in children.
      METHODS: Between October 2011 and May 2013, a total of 104 patients were managed
      using semirigid Ho:YAG ureterolithotripsy. Patient age, stone size and site,
      radiolucency, use of extraction devices, degree of hydronephrosis and size of
      ureteroscope were compared for operative time, success and complications.
      RESULTS: In all, 128 URS were done with a mean age of 4.7 years. The mean stones
      size was 11 mm. Success rate was 81.25 %. Causes of failure were 12.5 % access
      failure, 1.5 % extravasation and 4.7 % stone migration. Overall complications
      were 23.4 %. Failure of dilatation and extravasation were detected only in
      children <2 years old. Extravasation was significantly higher in smaller ureters
      and cases with stone size >15 mm. Stone migration was significantly higher in
      upper ureteric stones. CONCLUSIONS: Failure and complications rates in Ho:YAG
      ureterolithotripsy were significantly affected by younger age (<2 years), upper
      ureteric stones and smaller ureters but were not related to stone radiolucency or
      degree of hydronephrosis. Larger stones (>15 mm) were associated with increased
      complications. After multivariate analysis, the age of the patients remained
      significant predictor for failure of dilatation and stone migration, while size
      of the ureter was the only significant predicting factor for failure.

PMID- 23979151
TI  - Resistance patterns of nosocomial urinary tract infections in urology
      departments: 8-year results of the global prevalence of infections in urology
      study.
AB  - OBJECTIVE: To present the worldwide antibiotic resistance rates of uropathogens
      reported in nosocomial urinary tract infections (NAUTI) during the period of 2003
      2010. MATERIALS AND METHODS: Data from the Global Prevalence Study of Infections
      in Urology from the period of 2003-2010 were analyzed to evaluate the resistance
      rates of pathogens causing NAUTI. The web-based application was used to record
      data of investigators from urology departments participating in the study every
      year during the days allocated in November. Each center was allowed to enter data
      on a single day of the study. The point prevalence data was used to find
      differences among geographic regions and years by utilizing multiple logistic
      regression analysis. RESULTS: A total of 19,756 patients were hospitalized during
      the study period, and in 1,866 of them, NAUTI was reported. Proof of infection
      was reported in 1,395 patients. Resistance rates of all antibiotics tested other
      than imipenem against the total bacterial spectrum were higher than 10 % in all
      regions. Resistance to almost all pathogens was lowest in North Europe, and there
      is no single year where an outbreak of resistance has been detected. CONCLUSION:
      The resistance rates of most of the uropathogens against the antibiotics tested
      did not show significant trends of increase or decrease with Asia exhibiting the
      highest rates in general. The only antibiotic tested with an overall resistance
      rate below 10 % was imipenem. Knowledge of regional and local resistance data and
      prudent use of antibiotics are necessary to optimize antibiotic therapy in
      urological patients with NAUTI.

PMID- 23979152
TI  - Re: Imaging the urologic patient: the utility of intravenous pyelogram in the CT
      scan era.

PMID- 23979153
TI  - Lack of protease inhibitor resistance following treatment failure--too good to be
      true?
AB  - A 29-year-old man with recently diagnosed HIV infection and a CD4 cell count of
      225/mm3 began treatment with atazanavir (300 mg), ritonavir (100 mg),
      emtricitabine (200 mg), and tenofovir (300 mg) daily. For 18 months, he was
      treatment adherent and his plasma HIV RNA level was below the limit of detection.
      He then began a relationship with a new partner, who introduced him to
      methamphetamines. His medication adherence became erratic, and he missed
      appointments in clinic. Eventually. he was hospitalized for rehabilitation, and
      he resumed taking his medications on schedule. Following his discharge, he was
      found to have a plasma HIV RNA level of 11,400 copies/ml. Genotypic resistance
      testing revealed only an M184V mutation associated with emtricitabine resistance.
      A decision regarding his next treatment regimen needs to be made.

PMID- 23979154
TI  - Factor V, tissue factor pathway inhibitor, and east Texas bleeding disorder.
AB  - In a report reading like a fascinating detective story, Vincent and colleagues
      crack the mysterious case of east Texas bleeding disorder. They show that
      affected individuals have a mutation in exon 13 of the coagulation F5 gene that
      causes increased expression of an alternatively spliced transcript, which encodes
      a previously unrecognized factor V (FV) isoform they call FV-short. This FV
      isoform lacks a large portion of the B domain of FV, which is normally released
      upon the proteolytic activation of FV by thrombin and binds tightly to the
      coagulation regulator tissue factor pathway inhibitor-alpha (TFPIalpha). This
      interaction leads to an approximately 10-fold increase in the level of TFPIalpha
      circulating in plasma and a resultant anticoagulant effect that produces a
      hemorrhagic diathesis. 

PMID- 23979155
TI  - A "Tric" to tighten cell-cell junctions in the cochlea for hearing.
AB  - Tricellulin is a tricellular tight junction-associated membrane protein that
      controls movement of solutes at these specialized cell intersections. Mutations
      in the gene encoding tricellulin, TRIC, lead to nonsyndromic deafness. In this
      issue of the JCI, Nayak et al. created a gene-targeted knockin mouse in order to
      mimic the pathology of a human TRIC mutation. Deafness appears to be caused
      either by an increase in the K+ ion concentration around the basolateral surfaces
      of the outer hair cells or, alternatively, by an increase in small molecules such
      as ATP around the hair bundle, leading to cellular dysfunction and degeneration.
      Furthermore, the mice have features suggestive of syndromic hearing loss, which
      may have implications for care and treatment of patients harboring TRIC
      mutations. 

PMID- 23979156
TI  - Unshackling caspase-7 for cancer therapy.
AB  - Numerous solid tumors and hematologic malignancies acquire resistance to
      apoptosis-inducing chemotherapeutic drugs by downregulating the key effector
      caspase-3. These cells rely on caspase-7 to execute the apoptotic program, yet
      binding with XIAP constitutively inhibits active caspase-7 (p19/p12-CASP7). In
      this issue, Lin et al. describe how a newly synthesized drug is able to disrupt
      the XIAP:p19/p12-CASP7 complex and induce apoptosis in caspase-3-deficient cancer
      cells in vitro and in vivo. As this compound appears to exhibit minimal toxicity
      on normal tissues, it may represent a promising therapeutic agent to help treat
      caspase-3-deficient tumors. 

PMID- 23979157
TI  - Donor-associated malignancy in kidney transplant patients.
AB  - Skin cancer cells with donor genotype have been identified in allogeneic
      transplant patients; however, the donor contribution to the recipient's
      epithelial malignancy remains to be established. In this issue of the JCI,
      Verneuil et al. provide the first evidence for donor contribution to the
      malignant epithelium of skin squamous cell carcinoma in a kidney transplant
      recipient. This case report may have important implications for cancer research
      and clinical care of long-surviving kidney transplant patients. 

PMID- 23979158
TI  - A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia.
AB  - Neuropathic pain is characterized by mechanical allodynia induced by low
      threshold myelinated Abeta-fiber activation. The original gate theory of pain
      proposes that inhibitory interneurons in the lamina II of the spinal dorsal horn
      (DH) act as "gate control" units for preventing the interaction between innocuous
      and nociceptive signals. However, our understanding of the neuronal circuits
      underlying pain signaling and modulation in the spinal DH is incomplete. Using a
      rat model, we have shown that the convergence of glycinergic inhibitory and
      excitatory Abeta-fiber inputs onto PKCgamma+ neurons in the superficial DH forms
      a feed-forward inhibitory circuit that prevents Abeta input from activating the
      nociceptive pathway. This feed-forward inhibition was suppressed following
      peripheral nerve injury or glycine blockage, leading to inappropriate induction
      of action potential outputs in the nociceptive pathway by Abeta-fiber
      stimulation. Furthermore, spinal blockage of glycinergic synaptic transmission in
      vivo induced marked mechanical allodynia. Our findings identify a glycinergic
      feed-forward inhibitory circuit that functions as a gate control to separate the
      innocuous mechanoreceptive pathway and the nociceptive pathway in the spinal DH.
      Disruption of this glycinergic inhibitory circuit after peripheral nerve injury
      has the potential to elicit mechanical allodynia, a cardinal symptom of
      neuropathic pain. 

PMID- 23979159
TI  - Chronic epithelial kidney injury molecule-1 expression causes murine kidney
      fibrosis.
AB  - Acute kidney injury predisposes patients to the development of both chronic
      kidney disease and end-stage renal failure, but the molecular details underlying
      this important clinical association remain obscure. We report that kidney injury
      molecule-1 (KIM-1), an epithelial phosphatidylserine receptor expressed
      transiently after acute injury and chronically in fibrotic renal disease,
      promotes kidney fibrosis. Conditional expression of KIM-1 in renal epithelial
      cells (Kim1(RECtg)) in the absence of an injury stimulus resulted in focal
      epithelial vacuolization at birth, but otherwise normal tubule histology and
      kidney function. By 4 weeks of age, Kim1(RECtg) mice developed spontaneous and
      progressive interstitial kidney inflammation with fibrosis, leading to renal
      failure with anemia, proteinuria, hyperphosphatemia, hypertension, cardiac
      hypertrophy, and death, analogous to progressive kidney disease in humans.
      Kim1(RECtg) kidneys had elevated expression of proinflammatory monocyte
      chemotactic protein-1 (MCP-1) at early time points. Heterologous expression of
      KIM-1 in an immortalized proximal tubule cell line triggered MCP-1 secretion and
      increased MCP-1-dependent macrophage chemotaxis. In mice expressing a mutant,
      truncated KIM-1 polypeptide, experimental kidney fibrosis was ameliorated with
      reduced levels of MCP-1, consistent with a profibrotic role for native KIM-1.
      Thus, sustained KIM-1 expression promotes kidney fibrosis and provides a link
      between acute and recurrent injury with progressive chronic kidney disease.

PMID- 23979160
TI  - Human skin carcinoma arising from kidney transplant-derived tumor cells.
AB  - Tumor cells with donor genotype have been identified in human skin cancer after
      allogeneic transplantation; however, the donor contribution to the malignant
      epithelium has not been established. Kidney transplant recipients have an
      increased risk of invasive skin squamous cell carcinoma (SCC), which is
      associated with accumulation of the tumor suppressor p53 and TP53 mutations. In
      21 skin SCCs from kidney transplant recipients, we systematically assessed p53
      expression and donor/recipient origin in laser-microdissected p53+ tumor cells.
      In one patient, molecular analyses demonstrated that skin tumor cells had the
      donor genotype and harbored a TP53 mutation in codon 175. In a kidney graft
      biopsy performed 7 years before the skin SCC diagnosis, we found p53+ cells in
      the renal tubules. We identified the same TP53 mutation in these p53+ epithelial
      cells from the kidney transplant. These findings provide evidence for a donor
      epithelial cell contribution to the malignant skin epithelium in the recipient in
      the setting of allogeneic kidney transplantation. This finding has theoretical
      implications for cancer initiation and progression and clinical implications in
      the context of prolonged immunosuppression and longer survival of kidney
      transplant patients. 

PMID- 23979161
TI  - T cell-independent B cell activation induces immunosuppressive sialylated IgG
      antibodies.
AB  - Antigen-specific Abs are able to enhance or suppress immune responses depending
      on the receptors that they bind on immune cells. Recent studies have shown that
      pro- or antiinflammatory effector functions of IgG Abs are also regulated through
      their Fc N-linked glycosylation patterns. IgG Abs that are agalactosylated (non
      galactosylated) and asialylated are proinflammatory and induced by the
      combination of T cell-dependent (TD) protein antigens and proinflammatory
      costimulation. Sialylated IgG Abs, which are immunosuppressive, and Tregs are
      produced in the presence of TD antigens under tolerance conditions. T cell
      independent (TI) B cell activation via B cell receptor (BCR) crosslinking through
      polysaccharides or via BCR and TLR costimulation also induces IgG Abs, but the Fc
      glycosylation state of these Abs is unknown. We found in mouse experiments that
      TI immune responses induced suppressive sialylated IgGs, in contrast to TD
      proinflammatory Th1 and Th17 immune responses, which induced agalactosylated and
      asialylated IgGs. Transfer of low amounts of antigen-specific sialylated IgG Abs
      was sufficient to inhibit B cell activation and pathogenic immune reactions.
      These findings suggest an immune regulatory function for TI immune responses
      through the generation of immunosuppressive sialylated IgGs and may provide
      insight on the role of TI immune responses during infection, vaccination, and
      autoimmunity. 

PMID- 23979162
TI  - Coagulation factor V(A2440G) causes east Texas bleeding disorder via TFPIalpha.
AB  - The autosomal dominantly inherited east Texas bleeding disorder is linked to an
      A2440G variant in exon 13 of the F5 gene. Affected individuals have normal levels
      of coagulation factor V (FV) activity, but demonstrate inhibition of global
      coagulation tests. We demonstrated that the A2440G mutation causes upregulation
      of an alternatively spliced F5 transcript that results in an in-frame deletion of
      702 amino acids of the large activation fragment, the B domain. The approximately
      250-kDa FV isoform (FV-short), which can be fully activated by thrombin, is
      present in all A2440G carriers' plasma (n = 16). FV-short inhibits coagulation
      through an indirect mechanism by forming a complex with tissue factor pathway
      inhibitor-alpha (TFPIalpha), resulting in an approximately 10-fold increase in
      plasma TFPIalpha, suggesting that the TFPIalpha:FV-short complexes are retained
      in circulation. The TFPIalpha:FV-short complexes efficiently inhibit thrombin
      generation of both intrinsic and extrinsic coagulation pathways. These data
      demonstrate that the east Texas bleeding disorder-associated F5(A2440G) leads to
      the formation of the TFPIalpha:FV-short complex, which inhibits activation and
      propagation of coagulation.

PMID- 23979163
TI  - Combinatory approaches prevent preterm birth profoundly exacerbated by gene
      environment interactions.
AB  - There are currently more than 15 million preterm births each year. We propose
      that gene-environment interaction is a major contributor to preterm birth. To
      address this experimentally, we generated a mouse model with uterine deletion of
      Trp53, which exhibits approximately 50% incidence of spontaneous preterm birth
      due to premature decidual senescence with increased mTORC1 activity and COX2
      signaling. Here we provide evidence that this predisposition provoked preterm
      birth in 100% of females exposed to a mild inflammatory insult with LPS,
      revealing the high significance of gene-environment interactions in preterm
      birth. More intriguingly, preterm birth was rescued in LPS-treated Trp53
      deficient mice when they were treated with a combination of rapamycin (mTORC1
      inhibitor) and progesterone (P4), without adverse effects on maternal or fetal
      health. These results provide evidence for the cooperative contributions of two
      sites of action (decidua and ovary) toward preterm birth. Moreover, a similar
      signature of decidual senescence with increased mTORC1 and COX2 signaling was
      observed in women undergoing preterm birth. Collectively, our findings show that
      superimposition of inflammation on genetic predisposition results in high
      incidence of preterm birth and suggest that combined treatment with low doses of
      rapamycin and P4 may help reduce the incidence of preterm birth in high-risk
      women. 

PMID- 23979164
TI  - Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells.
AB  - RUNX1 is generally considered a tumor suppressor in myeloid neoplasms.
      Inactivating RUNX1 mutations have frequently been found in patients with
      myelodysplastic syndrome (MDS) and cytogenetically normal acute myeloid leukemia
      (AML). However, no somatic RUNX1 alteration was found in AMLs with leukemogenic
      fusion proteins, such as core-binding factor (CBF) leukemia and MLL fusion
      leukemia, raising the possibility that RUNX1 could actually promote the growth of
      these leukemia cells. Using normal human cord blood cells and those expressing
      leukemogenic fusion proteins, we discovered a dual role of RUNX1 in myeloid
      leukemogenesis. RUNX1 overexpression inhibited the growth of normal cord blood
      cells by inducing myeloid differentiation, whereas a certain level of RUNX1
      activity was required for the growth of AML1-ETO and MLL-AF9 cells. Using a mouse
      genetic model, we also showed that the combined loss of Runx1/Cbfb inhibited
      leukemia development induced by MLL-AF9. RUNX2 could compensate for the loss of
      RUNX1. The survival effect of RUNX1 was mediated by BCL2 in MLL fusion leukemia.
      Our study unveiled an unexpected prosurvival role for RUNX1 in myeloid
      leukemogenesis. Inhibiting RUNX1 activity rather than enhancing it could be a
      promising therapeutic strategy for AMLs with leukemogenic fusion proteins. 

PMID- 23979165
TI  - Multi-step inhibition explains HIV-1 protease inhibitor pharmacodynamics and
      resistance.
AB  - HIV-1 protease inhibitors (PIs) are among the most effective antiretroviral
      drugs. They are characterized by highly cooperative dose-response curves that are
      not explained by current pharmacodynamic theory. An unresolved problem affecting
      the clinical use of PIs is that patients who fail PI-containing regimens often
      have virus that lacks protease mutations, in apparent violation of fundamental
      evolutionary theory. Here, we show that these unresolved issues can be explained
      through analysis of the effects of PIs on distinct steps in the viral life cycle.
      We found that PIs do not affect virion release from infected cells but block
      entry, reverse transcription, and post-reverse transcription steps. The overall
      dose-response curves could be reconstructed by combining the curves for each step
      using the Bliss independence principle, showing that independent inhibition of
      multiple distinct steps in the life cycle generates the highly cooperative dose
      response curves that make these drugs uniquely effective. Approximately half of
      the inhibitory potential of PIs is manifest at the entry step, likely reflecting
      interactions between the uncleaved Gag and the cytoplasmic tail (CT) of the Env
      protein. Sequence changes in the CT alone, which are ignored in current clinical
      tests for PI resistance, conferred PI resistance, providing an explanation for PI
      failure without resistance. 

PMID- 23979166
TI  - Targeting the XIAP/caspase-7 complex selectively kills caspase-3-deficient
      malignancies.
AB  - Caspase-3 downregulation (CASP3/DR) in tumors frequently confers resistance to
      cancer therapy and is significantly correlated with a poor prognosis in cancer
      patients. Because CASP3/DR cancer cells rely heavily on the activity of caspase-7
      (CASP7) to initiate apoptosis, inhibition of activated CASP7 (p19/p12-CASP7) by X
      linked inhibitor of apoptosis protein (XIAP) is a potential mechanism by which
      apoptosis is prevented in those cancer cells. Here, we identify the pocket
      surrounding the Cys246 residue of p19/p12-CASP7 as a target for the development
      of a protein-protein interaction (PPI) inhibitor of the XIAP:p19/p12-CASP7
      complex. Interrupting this PPI directly triggered CASP7-dependent apoptotic
      signaling that bypassed the activation of the apical caspases and selectively
      killed CASP3/DR malignancies in vitro and in vivo without adverse side effects in
      nontumor cells. Importantly, CASP3/DR combined with p19/p12-CASP7 accumulation
      correlated with the aggressive evolution of clinical malignancies and a poor
      prognosis in cancer patients. Moreover, targeting of this PPI effectively killed
      cancer cells with multidrug resistance due to microRNA let-7a-1-mediated CASP3/DR
      and resensitized cancer cells to chemotherapy-induced apoptosis. These findings
      not only provide an opportunity to treat CASP3/DR malignancies by targeting the
      XIAP:p19/p12-CASP7 complex, but also elucidate the molecular mechanism underlying
      CASP3/DR in cancers. 

PMID- 23979168
TI  - Short-term cuprizone feeding induces selective amino acid deprivation with
      concomitant activation of an integrated stress response in oligodendrocytes.
AB  - Cuprizone [bis(cyclohexylidenehydrazide)]-induced toxic demyelination is an
      experimental approach frequently used to study de- and re-myelination in the
      central nervous system. In this model, mice are fed with the copper chelator
      cuprizone which leads to oligodendrocyte apoptosis and subsequent microgliosis,
      astrocytosis, and demyelination. The underlying mechanisms of cuprizone-induced
      oligodendrocyte death are still unknown. We analysed differences in amino acid
      levels after short-term cuprizone exposure (i.e., 4 days). Furthermore, an amino
      acid response (AAR) pathway activated in oligodendrocytes after cuprizone
      intoxication was evaluated. Short-term cuprizone exposure resulted in a selective
      decrease of alanine, glycine, and proline plasma levels, which was paralleled by
      an increase of apoptotic cells in the liver and a decrease of alanine
      aminotransferase in the serum. These parameters were paralleled by
      oligodendrocyte apoptosis and the induction of an AAR with increased expression
      of the transcription factors ATF-3 and ATF-4 (activating transcription factor-3
      and -4). Immunohistochemistry revealed that ATF-3 is exclusively expressed by
      oligodendrocytes and localized to the nuclear compartment. Our results suggest
      that cuprizone-induced liver dysfunction results in amino acid starvation and in
      consequence to the activation of an AAR. We propose that this stress response
      modulates oligodendrocyte viability in the cuprizone animal model.

PMID- 23979171
TI  - Abstracts of the 24th International Symposium on the Autonomic Nervous System,
      Kohala Coast, Hawaii, October 23-26, 2013.

PMID- 23979169
TI  - [Arthrodesis and endoprostheses of the ankle joint: indications, techniques and
      pitfalls].
AB  - If adequate conservative measures for the treatment of end-stage ankle
      osteoarthritis have failed, surgery may be taken into consideration. After
      exorbitant failure rates in the beginning of total ankle replacement, nowadays
      this kind of treatment has regained lot of interest and has become a viable
      alternative to ankle fusion. The correct indication and a precise explanation of
      the surgical procedure, outcomes and potential complications provide a solid base
      for future success.Currently, there is no doubt that total ankle replacement has
      become an important player in the treatment of symptomatic and debilitating end
      stage ankle arthritis. With increasing number of patients who undergo total ankle
      replacement the experience with this kind of procedure increases too. As a
      consequence several surgeons have started to stretch indications favoring total
      ankle replacement. However, it must be mentioned here, despite progress in terms
      of improved anatomical and biomechanical understanding of the hindfoot and
      improved surgical techniques and instruments, total ankle replacement and ankle
      fusion remain challenging and difficult procedures. We provide a review article
      including an overview of the relevant techniques. This article should serve as
      rough guide for surgeons and help in decision-making regarding total ankle
      replacement and ankle fusion. 

PMID- 23979167
TI  - Tricellulin deficiency affects tight junction architecture and cochlear hair
      cells.
AB  - The two compositionally distinct extracellular cochlear fluids, endolymph and
      perilymph, are separated by tight junctions that outline the scala media and
      reticular lamina. Mutations in TRIC (also known as MARVELD2), which encodes a
      tricellular tight junction protein known as tricellulin, lead to nonsyndromic
      hearing loss (DFNB49). We generated a knockin mouse that carries a mutation
      orthologous to the TRIC coding mutation linked to DFNB49 hearing loss in humans.
      Tricellulin was absent from the tricellular junctions in the inner ear epithelia
      of the mutant animals, which developed rapidly progressing hearing loss
      accompanied by loss of mechanosensory cochlear hair cells, while the endocochlear
      potential and paracellular permeability of a biotin-based tracer in the stria
      vascularis were unaltered. Freeze-fracture electron microscopy revealed
      disruption of the strands of intramembrane particles connecting bicellular and
      tricellular junctions in the inner ear epithelia of tricellulin-deficient mice.
      These ultrastructural changes may selectively affect the paracellular
      permeability of ions or small molecules, resulting in a toxic microenvironment
      for cochlear hair cells. Consistent with this hypothesis, hair cell loss was
      rescued in tricellulin-deficient mice when generation of normal endolymph was
      inhibited by a concomitant deletion of the transcription factor, Pou3f4. Finally,
      comprehensive phenotypic screening showed a broader pathological phenotype in the
      mutant mice, which highlights the non-redundant roles played by tricellulin. 

PMID- 23979170
TI  - Editorial. Third year of my stewardship.

PMID- 23979172
TI  - Carbon nanotube-encapsulated drug penetration through the cell membrane: an
      investigation based on steered molecular dynamics simulation.
AB  - Understanding the penetration mechanisms of carbon nanotube (CNTs)-encapsulated
      drugs through the phospholipid bilayer cell membrane is an important issue for
      the development of intracellular drug delivery systems. In the present work,
      steered molecular dynamics (SMD) simulation was used to explore the possibility
      of penetration of a polar drug, paclitaxel (PTX), encapsulated inside the CNT,
      through a dipalmitoylphosphatidylcholine bilayer membrane. The interactions
      between PTX and CNT and between PTX and the confined water molecules inside the
      CNT had a significant effect on the penetration process of PTX. The results
      reveal that the presence of a PTX molecule increases the magnitude of the pulling
      force. The effect of pulling velocity on the penetration mechanism was also
      investigated by a series of SMD simulations, and it is shown that the pulling
      velocity had a significant effect on pulling force and the interaction between
      lipid bilayer and drug molecule. 

PMID- 23979173
TI  - Functional characterization of SdcF from Bacillus licheniformis, a homolog of the
      SLC13 Na+/dicarboxylate transporters.
AB  - The SdcF transporter from Bacillus licheniformis (gene BL02343) is a member of
      the divalent anion sodium symporter (DASS)/SLC13 family that includes
      Na+/dicarboxylate transporters from bacteria to humans. SdcF was functionally
      expressed in Escherichia coli (BL21) and assayed in right side out membrane
      vesicles. ScdF catalyzed the sodium-coupled transport of succinate and alpha
      ketoglutarate. Succinate transport was strongly inhibited by malate, fumarate,
      tartrate, oxaloacetate and L-aspartate. Similar to the other DASS transporters,
      succinate transport by SdcF was inhibited by anthranilic acids, N-(p
      amylcinnamoyl) anthranilic acid and flufenamate. SdcF transport was cation
      dependent, with a K0.5 for sodium of ~1.5 mM and a K0.5 for Li+ of ~40 mM.
      Succinate transport kinetics by SdcF were sigmoidal, suggesting that SdcF may
      contain two cooperative substrate binding sites. The results support an ordered
      binding mechanism for SdcF in which sodium binds first and succinate binds last.
      We conclude that SdcF is a secondary active transporter for four- and five-carbon
      dicarboxylates that can use Na+ or Li+ as a driving cation.

PMID- 23979174
TI  - Providing patients with pharmacogenetic test results affects adherence to statin
      therapy: results of the Additional KIF6 Risk Offers Better Adherence to Statins
      (AKROBATS) trial.
AB  - Despite the clinical benefit of statin therapy and the numerous strategies used
      to improve adherence, no strategy has used direct communication of genetic test
      results to the patient as an adherence and persistence motivator. We investigated
      in a real-world setting the effect of a process of providing KIF6 test results
      and risk information directly to 647 tested patients on 6-month statin adherence
      (proportion of days covered (PDC)) and persistence compared with concurrent non
      tested matched controls. Adjusted 6-month statin PDC was significantly greater in
      tested patients: 0.77 (95% confidence interval (CI) 0.72-0.82) vs controls 0.68
      (95% CI 0.63-0.73), P<0.0001. Significantly more tested patients were adherent
      (PDC?0.80) (63.4% (59.6-67.1%) vs 45.0% (41.1-48.8%), P<0.0001) and persisted on
      therapy (69.1% (65.4-72.5%) vs 53.3% (49.4-57.1%), P<0.0001). Similar results
      were observed in a secondary comparison with 779 unmatched patients who declined
      testing. The Additional KIF6 Risk Offers Better Adherence to Statins trial
      provides the first evidence that pharmacogenetic testing may modify patient
      adherence. 

PMID- 23979175
TI  - Transcriptomic analysis of human retinal surgical specimens using jouRNAI.
AB  - Retinal detachment (RD) describes a separation of the neurosensory retina from
      the retinal pigmented epithelium (RPE). The RPE is essential for normal function
      of the light sensitive neurons, the photoreceptors. Detachment of the retina from
      the RPE creates a physical gap that is filled with extracellular fluid. RD
      initiates cellular and molecular adverse events that affect both the neurosensory
      retina and the RPE since the physiological exchange of ions and metabolites is
      severely perturbed. The consequence for vision is related to the duration of the
      detachment since a rapid reapposition of the two tissues results in the
      restoration of vision (1). The treatment of RD is exclusively surgical. Removal
      of vitreous gel (vitrectomy) is followed by the removal non essential part of the
      retina around the detached area to favor retinal detachment. The removed retinal
      specimens are res nullius (nothing) and consequently normally discarded. To
      recover RNA from these surgical specimens, we developed the procedure jouRNAl
      that allows RNA conservation during the transfer from the surgical block to the
      laboratory. We also standardized a protocol to purify RNA by cesium chloride
      ultracentrifugation to assure that the purified RNAs are suitable for global gene
      expression analysis. The quality of the RNA was validated both by RT-PCR and
      microarray analysis. Analysis of the data shows a simultaneous involvement of
      inflammation and photoreceptor degeneration during RD.

PMID- 23979176
TI  - Zucchini tigre mosaic virus is a distinct potyvirus in the papaya ringspot virus
      cluster: molecular and biological insights.
AB  - In recent years, three new potyviruses have been described in the papaya ringspot
      virus (PRSV) cluster. In addition, two types of PRSV are recognized, type W,
      infecting cucurbit plants, and type P, infecting papaya and also cucurbits. A
      third type, PRSV-T, was also partially described in Guadeloupe. Complete genome
      sequencing of four PRSV-T isolates showed that this virus is a related virus that
      is distinct from PRSV, and the name zucchini tigre mosaic virus (ZTMV) is
      proposed, in reference to the typical symptoms observed in zucchini squash.
      Eleven other viral isolates from different geographic origins were confirmed as
      ZTMV isolates using the complete sequence of the cylindrical inclusion (CI)
      coding region, whereas pairwise sequence similarities in the coat protein (CP)
      coding region did not unambiguously distinguish ZTMV isolates from PRSV isolates.
      The use of the CI coding region for species demarcation appears more suitable
      than the CP coding region for closely related viruses. Principal coordinates
      analysis based on the biological behavior of the viral isolates studied clustered
      PRSV-P, PRSV-W and ZTMV isolates into three different groups. Therefore, ZTMV is
      different from PRSV in its molecular and biological properties. 

PMID- 23979177
TI  - Current and future therapies for hepatitis C virus infection: from viral proteins
      to host targets.
AB  - Hepatitis C virus (HCV) infection is the most important problem across the world.
      It causes acute and chronic liver infection. Different approaches are in use to
      inhibit HCV infection, including small organic compounds, siRNA, shRNA and
      peptide inhibitors. This review article summarizes the current and future
      therapies for HCV infection. PubMed and Google Scholar were searched for articles
      published in English to give an insight into the current inhibitors against this
      life-threatening virus. HCV NS3/4A protease inhibitors and nucleoside/nucleotide
      inhibitors of NS5B polymerase are presently in the most progressive stage of
      clinical development, but they are linked with the development of resistance and
      viral breakthrough. Boceprevir and telaprevir are the two most important protease
      inhibitors that have been approved recently for the treatment of HCV infection.
      These two drugs are now the part of standard-of-care treatment (SOC). There are
      also many other drugs in phase III of clinical development. When exploring the
      various host-cell-targeting compounds, the most hopeful results have been
      demonstrated by cyclophilin inhibitors. The current SOC treatment of HCV
      infection is Peg-interferon, ribavirin and protease inhibitors (boceprevir or
      telaprevir). The future treatment of this life-threatening disease must involve
      combinations of therapies hitting multiple targets of HCV and host factors. It is
      strongly expected that the near future, treatment of HCV infection will be a
      combination of direct-acting agents (DAA) without the involvement of interferon
      to eliminate its side effects. 

PMID- 23979178
TI  - Combined administration of oseltamivir and hochu-ekki-to (TJ-41) dramatically
      decreases the viral load in lungs of senescence-accelerated mice during influenza
      virus infection.
AB  - To enhance the effect of anti-influenza-virus agent treatment, the effect of
      combined administration of oseltamivir phosphate and hochu-ekki-to (Japanese
      traditional herbal medicine, HET) on early viral clearance was examined.
      Senescence-accelerated mice were given HET in drinking water for 2 weeks,
      followed by intranasal infection with influenza A virus strain PR8. After 4 hours
      of infection, oseltamivir was administered orally for 5 days. The viral loads in
      the lungs of the group receiving combined treatment were dramatically lower when
      compared with the viral loads in the lungs of the group receiving oseltamivir
      alone. HET significantly increased the induction of IL-1beta and TNF-alpha in the
      lungs of PR8-infected mice and stimulated alveolar macrophage phagocytosis. From
      these results, we conclude that these functions may be responsible the increased
      effect on viral load reduction. Here, we show that the combined administration of
      oseltamivir and HET is very useful for influenza treatment in senescence
      accelerated mice.

PMID- 23979179
TI  - Meal induced gut hormone secretion is altered in aerobically trained compared to
      sedentary young healthy males.
AB  - Postprandial insulin release is lower in healthy aerobically trained (T) compared
      to untrained (UT) individuals. This may be mediated by a lower release of the two
      incretin hormones [glucagon like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP)] in T. The aim of this study was to assess and
      compare gut hormone response and satiety changes after a liquid meal intake in
      young, healthy T and UT males. Postprandial gut hormone release and subjective
      feelings of hunger, satiety, fullness and prospective food consumption were
      assessed before and frequently for the following 3 h after a 200 ml liquid meal
      (1,260 kJ and 27, 41 and 32 energy % as protein, carbohydrates and fat,
      respectively) in ten T and ten UT young, healthy male subjects. The insulin and
      GIP responses were markedly lower in T than UT and correlated during the first 30
      min after the liquid meal. Baseline GLP-1 concentration was higher in T versus
      UT, but the response in the following 3 h after a liquid meal was similar in T
      and UT. Satiety measures did not differ between groups throughout the test. It is
      possible that in aerobically T subjects, a lower GIP release is partly
      responsible for a lower postprandial incretin stimulated insulin secretion.

PMID- 23979180
TI  - Compounding for geriatric patients.

PMID- 23979181
TI  - Estrogen replacement therapy in the treatment of Alzheimer's disease.

PMID- 23979182
TI  - Lollipops: the evolution of a dosage form.

PMID- 23979184
TI  - Treatment of pain with a topically applied combination of indomethacin and
      piroxicam.

PMID- 23979183
TI  - Comopounding in history: the road to wellville.

PMID- 23979185
TI  - Medications discontinued in the United States.

PMID- 23979186
TI  - Basics of compounding: iontophoresis.

PMID- 23979187
TI  - The treatment of canine atopic disease.

PMID- 23979188
TI  - A Review of pH and Osmolarity.

PMID- 23979189
TI  - Stability of Ampicillin Sodium, Nafcillin Sodium, And Oxacillin Sodium in
      AutoDose Infusion System Bags.
AB  - The objective of this study was to evaluate the physical and chemical stability
      of ampicillin sodium 1g/100mL, nafcillin sodium 1g/100mL, and oxacillin sodium
      1g/100mL, each of which was admixed in 0.9% sodium chloride injection and
      packaged in an AutoDose Infusion System bag. Triplicate test samples were
      prepared by reconstituting the penicillin antibiotics and bringing the required
      amount of each drug to a final volume of 100 mL with 0.9% sodium chloride
      injection. The test solutions were packaged in AutoDose Bags, which are ethylene
      vinyl acetate plastic containers designed for use in the AutoDose Infusion
      System. Samples were stored protected from light and were evaluated at
      appropriate intervals for up to 7 days at 23 deg C and up to 30 days at 4 deg C.
      Physical stability was assessed by means of a multistep evaluation procedure that
      included both turbidimetric and particulate measurement as well as visual
      inspection. Chemical stability was assesed with stability-indicating high
      perofrmance liquid chromatographic (HPLC) analytical techniques based on the
      determination of drug concentrations initially and at appropriate intervals over
      the study periods. All the penicillin admixtures were initially clear when viewed
      in normal fluorescent room light. When the admixtures were viewed with a Tyndall
      beam, a trace haze was observed with the ampicillin sodium and nafcillin sodium
      mixtures but not with the oxacillin sodium mixture. Measured turbidity and
      particulate content were low and exhibited little change in the ampicillin sodium
      and oxacillin sodium samples throughout the study. The nafcillin sodium samples
      stored at room temperature remained clear, but a microprecipitate developed in
      the refrigerated samples between 14 and 21 days of storage. All samples were
      essentially colorless throughout the study. HPLC analysis indicated some
      decomposition in the samples. Ampicillin sodium, which was the least stable,
      exhibited a 10% loss after 24 hours at 23 deg C. In the samples stored at 4 deg
      C, ampicillin losses were 6% and 11% after 3 days and 5 days,respecively.
      Nafcillin sodium exhiibited a 10% loss after 5 days at 23 deg C. Less than 3%
      loss occurred after 14 days at 4 deg C, but the microprecipitation that developed
      resulted in the termination of that portion of the study. Oxacillin sodium was
      the most stable; it exhibited less than a 10% loss after 7 days at 23 deg C and
      less than a 5% loss after 30 days at 4 deg C. Ampicillin sodium, nafcillin
      sodium, and oxacillin sodium exhibited physical and chemical stability consistent
      with previous studies on these drugs. The AutoDose Infusion System bags did not
      adversely affect the physical and chemical stability of those three penicillin
      antibiotics. 

PMID- 23979190
TI  - Compatibility screening of precedex during simulated y-site administration with
      other drugs.
AB  - The physical compatibility of Precedex with 95 other drugs during simulated Y
      site injection was evaluated by visual observation, turbidity measurement, and
      electronic particle content assessment (when appropriate). Five-milliliter
      samples of Precedex 4 micrograms/mL in 0.9% sodium chloride injection were
      combined with 5 mL of each of 95 other drugs. The other test drugs included anti
      infectives, analgesics, antihistamines, diuretics, steroids, and other supportive
      care drugs undiluted or diluted in 0.9% sodium chloride injection or 5% dextrose
      injection (for amphotericin B). Visual examinations were performed with the
      unaided eye in normal diffuse fluorescent light and with a Tyndall beam (a high
      intensity monodirectional light beam) to enhance the visualization of small
      particles and low-level turbidity. The turbidity of each sample was measured as
      well, as was the particle content of samples with no visible incompatibility.
      Evaluation of the samples was performed initially and at 1 and 4 hours after
      preparation. Ninety-three of the 95 test drugs were compatible with the Precedex
      dilution during the 4-hour observation period; however, both amphotericin B and
      diazepam resulted in precipitation. Precedex, which is incompatible, with
      amphotericin B and diazepam, should not be administered simultaneously with those
      drugs. 

PMID- 23979191
TI  - Stability of cefotaxime sodium after reconstitution in 0.9% sodium chloride
      injection and storage in polypropylene syringes for pediatric use.
AB  - A stability-indicating high-performance liquid chromatographic assay method was
      used to study the stability of cefotaxime sodium (50 mg/mL) in 0.9% sodium
      chloride injection in polypropylene syringes at 5 deg C and 25 deg C. The
      concentrations of the drug were directly related to peak heights, and the percent
      relative standard deviation based on 5 injections was 1.1. There were at least
      three products of decomposition that separated from the intact drug. At 5 deg C,
      the decomposition was less than 3% when stored for 18 days, and at 25 deg C, the
      loss in potency was less than 10% after 1 day of storage. When stored for 18 days
      at 5 deg C, the pH value of the injection decreased from 5.3 to 5.0 when stored
      at 25 deg C for 1 day. The drug was not absorbed onto the syringes, and the
      intensity of the light yellow color did not change significantly during storage
      at 5 deg C but increased during storage at 25 deg C.

PMID- 23979192
TI  - A naturally occurring amino acid substitution in the voltage-dependent sodium
      channel selectivity filter affects channel gating.
AB  - The pore of sodium channels contains a selectivity filter made of 4 amino acids,
      D/E/K/A. In voltage sensitive sodium channel (Nav) channels from jellyfish to
      human the fourth amino acid is Ala. This Ala, when mutated to Asp, promotes slow
      inactivation. In some Nav channels of pufferfishes, the Ala is replaced with Gly.
      We studied the biophysical properties of an Ala-to-Gly substitution (A1529G) in
      rat Nav1.4 channel expressed in Xenopus oocytes alone or with a beta1 subunit.
      The Ala-to-Gly substitution does not affect monovalent cation selectivity and
      positively shifts the voltage-dependent inactivation curve, although co
      expression with a beta1 subunit eliminates the difference between A1529G and WT.
      There is almost no difference in channel fast inactivation, but the beta1 subunit
      accelerates WT current inactivation significantly more than it does the A1529G
      channels. The Ala-to-Gly substitution mainly influences the rate of recovery from
      slow inactivation. Again, the beta1 subunit is less effective on speeding
      recovery of A1529G than the WT. We searched Nav channels in numerous databases
      and noted at least four other independent Ala-to-Gly substitutions in Nav
      channels in teleost fishes. Thus, the Ala-to-Gly substitution occurs more
      frequently than previously realized, possibly under selection for alterations of
      channel gating. 

PMID- 23979193
TI  - Human farnesyl pyrophosphate synthase inhibition by nitrogen bisphosphonates: a
      3D-QSAR study.
AB  - We report the results of a comparative molecular field analysis and comparative
      molecular similarity index analysis of the human farnesyl pyrophosphate synthase
      (FPPS) inhibition by nitrogen bisphosphonates (NBPs) taking into account their
      time-dependent inhibition efficacies. The 3D-QSAR models obtained provide steric,
      electrostatic and hydrophobic contour maps consistent with the interactions into
      the active site of human FPPS observed in available crystallographic structures.
      Furthermore, the 3D-QSAR models obtained provide accurately IC50 values of the
      NBPs of the training set. The predictive ability of these 3D-QSAR models was
      found to rely on the choice of biologically active conformations of the target
      molecules and on a careful examination of the protonation status of the NBPs in
      the training set. The best models obtained can be useful to predict biological
      values of a high number of NBPs that have been used for the treatment of
      different diseases as potential inhibitors of the activity of the FPPS enzyme. 

PMID- 23979194
TI  - Discover binding pathways using the sliding binding-box docking approach:
      application to binding pathways of oseltamivir to avian influenza H5N1
      neuraminidase.
AB  - Drug binding and unbinding are transient processes which are hardly observed by
      experiment and difficult to analyze by computational techniques. In this paper,
      we employed a cost-effective method called "pathway docking" in which molecular
      docking was used to screen ligand-receptor binding free energy surface to reveal
      possible paths of ligand approaching protein binding pocket. A case study was
      applied on oseltamivir, the key drug against influenza a virus. The equilibrium
      pathways identified by this method are found to be similar to those identified in
      prior studies using highly expensive computational approaches. 

PMID- 23979195
TI  - Personalized medicine: Lung Cancer leads the way.

PMID- 23979196
TI  - A year of anaplastic large cell kinase testing for lung carcinoma: pathological
      and technical perspectives.
AB  - BACKGROUND: An in-frame fusion protein between echinoderm microtubule-associated
      protein-like 4 (EML4) and anaplastic large cell kinase (ALK) genes is seen in
      some non-small cell lung cancer (NSCLC). EML4-ALK demonstrates constitutive
      kinase activity. These ALK-positive lung carcinomas have been shown to respond to
      ALK kinase inhibitors. ALK gene rearrangement is commonly detected using
      fluorescent in situ hybridization (FISH). AIMS: To study the pathological
      features of ALK positive and negative NSCLC and evaluate the causes of
      uninterpretable FISH results. MATERIALS AND METHODS: This is a retrospective,
      observational study. The molecular pathology records of patients on whom test for
      ALK had been performed in a period of 1 year (February 2012 to February 2013)
      were accessioned. A total 224 cases were identified. Histological features were
      reviewed. The in situ hybridization was performed using Vysis ALK Dual Color
      Break Apart Rearrangement Probe (Abbott Molecular Inc.). Signal interpretation
      under the fluorescent microscope was performed in accordance with College of
      American Pathologists guidelines. RESULTS: Five patients showed ALK gene
      rearrangement, 182 were negative and 37 cases were uninterpretable. Five patients
      with ALK gene rearrangement had a mean age of 48 years and the male to female
      ratio was 2:3. In the ALK negative cases, the mean age was 54 years and male to
      female ratio was 3.2:1. Histologically, amongst the rearranged cases, three
      showed solid pattern, one showed acinar and one showed acinar with signet ring
      cells on histology. CONCLUSION: The percentage of ALK gene rearrangement was 2.7%
      (excluding the uninterpretable cases). These ALK positive patients were
      relatively younger than ALK negative patients. Solid pattern on histology was
      associated with ALK positivity. In a quarter of the uninterpretable results, the
      material submitted was fixed and processed outside.

PMID- 23979197
TI  - Epidermal growth factor receptor mutation in non-small-cell lung carcinomas: a
      retrospective analysis of 1036 lung cancer specimens from a network of tertiary
      cancer care centers in India.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) mutation plays a vital role
      in the prognosis of patients with lung cancer. However, there is a dearth of
      studies on EGFR mutation in Indian population. In this retrospective study
      conducted at a network of tertiary cancer care centers across India, we evaluated
      the proportion of EGFR mutation in patients with non-small-cell lung carcinomas
      (NSCLC). MATERIALS AND METHODS: A total of 1036 cases of non-small lung cancer
      were assessed for EGFR mutation status using Scorpion amplified refractory
      mutation system real time polymerase chain reaction method from fine needle
      aspiration cytology core biopsy, pleural fluid and cell blocks. For a few cases,
      macro dissection of tumor from H and E slides was also performed for EGFR
      analysis. EGFR Status was assessed for the most commonly known driver mutations
      in Exons 18, 19, 20 and 21, which contributes to a total of 29 somatic mutations
      including the resistance mutation T790M. RESULTS: Around 39% of the cohort was
      female and 61% were male. Mutation was positive in 40.3% and negative (wild type)
      in 59.7%. There was 1.8% mutation in exon 18, 24.6% in exon 19, 1.6% in exon 20
      and 12.8% in exon 21. 38.2% had a mutation in a single site and 1.1% had a
      mutation in two sites. Overall mutation was significant in females (50.5% vs.
      33.9%) compared with males (chi2 = 28.3, P < 0.001). Mutation was significant in
      exon 21 (16.8% vs. 10.3%, chi2 = 9.44, P = 0.002) and exon 19 (30.7% vs. 20.7%,
      chi2 = 13.2, P < 0.001) in females compared with males. CONCLUSION: EGFR is
      expressed differentially/mutated in patients with NSCLC. Further studies to
      unravel the predictors for acquired genetic alterations of EGFR are needed.

PMID- 23979198
TI  - Clinicopathologic features of non-small cell lung cancer in India and correlation
      with epidermal growth factor receptor mutational status.
AB  - INTRODUCTION: We performed retrospective analysis of 106 patients with lung
      cancer for which formalin-fixed paraffin-embedded tissues was available. Their
      epidermal growth factor receptor (EGFR) mutation status and treatment outcomes
      are described. MATERIALS AND METHODS: All patients with confirmed non-small cell
      lung cancer (NSCLC) during Jan 2008 to Dec 2010 were included. EGFR sequencing
      was performed with ABI PRISM 310 genetic analyzer. RESULTS: Forty-two (39.6%)
      patients had mutation in one of the four exons characterized. Patients whose EGFR
      mutational status was not available at presentation before the start of treatment
      were started on chemotherapy, n = 46 (43.39%). If EGFR mutational analysis was
      available and mutations were present, the patients were started on either upfront
      tyrosine kinase inhibitor (TKI), n = 15 (14.15%) or if on chemotherapy arm were
      allowed to finish six cycles and then start with maintenance TKIs, n = 26
      (24.52%). The median progression free survival for patients with and without
      mutations was 11 months (95% CI,7-14) and 9 months (95% CI,7-10) respectively. A
      median PFS of 14 months (95%CI, 12-16) was seen in the mutation-positive group
      that received both chemotherapy followed by switch maintenance with TKIs versus 8
      months (95%CI, 7-8 months) in the group that received only TKI. CONCLUSION: The
      prevalence of EGFR mutations in this population of NSCLC patients was 39.6% with
      exon 19 mutation being the most common. The observed benefit of addition of
      chemotherapy over TKI in EGFR mutation-positive group raises the question, can we
      offer the therapy of chemotherapy-TKI combination to EGFR mutation-positive lung
      cancer patients as shown in the present study.

PMID- 23979199
TI  - Molecular epidemiology of epidermal growth factor receptor mutations in lung
      cancers in Indian population.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer related mortality world
      wide and amongst males in India. The discovery of tyrosine kinase inhibitors
      holds a ray of hope for a subset of lung cancer patients, which have activating
      epidermal growth factor receptor (EGFR) mutations. Much of the preliminary data
      on frequency of EGFR mutations emanated from Western studies, which reported EGFR
      mutation rates of 10-15%. However, studies from Asian countries report a much
      higher frequency of EGFR mutations, not only in the male population, but also in
      females. AIM: The object of this study was to share the author's experience of
      EGFR mutation testing in 402 lung cancer patients as no large-scale study
      addressing the issue has been published from India. MATERIALS AND METHODS:
      Formalin fixed paraffin embedded tissues were analyzed for EGFR exon 19 deletions
      and exon 21 point mutation by length analysis of fluorescently labeled polymerase
      chain reaction products on Applied Biosystems Inc. 310 genetic analyzer. RESULTS:
      Out of 402 samples, 35 samples could not be analyzed because of poor
      deoxyribonucleic acid material. Thus of the remaining 367 cases analyzed, EGFR
      mutations were found in 118 patients (32%). Mutations were equally distributed
      between males (50%) and females (50%). Majority of the mutations were seen in
      adenocarcinoma subtype (90%). Exon 19 mutations accounted for 76% while exon 21
      mutations accounted for 24% of the mutations. SUMMARY: EGFR mutation frequency is
      higher in Indian population vis-a-vis Caucasian population, but lower than that
      reported in the East Asian population. A significantly higher number of males
      also harbor EGFR mutations.

PMID- 23979201
TI  - Metronomics in low and middle income countries: India showing the way!

PMID- 23979200
TI  - Epidermal growth factor receptor mutation subtypes and geographical distribution
      among Indian non-small cell lung cancer patients.
AB  - BACKGROUND: The Medical Oncology Department at Tata Memorial Hospital, the single
      largest tertiary cancer care center in Asia, receives in-house registered and
      referral patient samples from all parts of the country. Our recent studies
      establish 23% EGFR mutation frequency among Indian population. Here, we extend
      our study and report further analysis of distribution of different types of EGFR
      mutations in 1018 non small cell lung cancer patient, and its co-relation with
      clinical parameters and geographical variations across the country. MATERIAL AND
      METHODS: This study is a retrospective analysis on all the patients who were
      referred for EFGR testing as a routine service over a 1.5 year period. This was
      part of standard care. EGFR kinase domain mutations in exon 18-21 were probed by
      TaqMan probe-based assays in 1018 NSCLC patients. RESULTS AND DISCUSSION: While
      EGFR exon 19 mutations, the most frequent EGFR mutation, were found be higher
      among non smokers females, we find surprisingly higher incidence of exon 21
      mutations among EGFR mutation positive male smokers of Indian ethnicity.
      Furthermore, as Indian population is known to be composed of a gradient admixture
      of Ancestral North Indian (with genetic influence from Middle Easterners, Central
      Asians, and Europeans harboring variant EGFR mutation frequency) and Ancestral
      South Indians, as a paradox our study indicates comparable EGFR mutation
      frequency across different geographical locations within India CONCLUSION:
      Geographically there is uniform distribution in the EGFR mutation frequency
      within India. Further more, while exon 19 mutations are predominant among non
      smokers, higher incidence of exon 21 mutations exists among EGFR mutation
      positive male smokers of Indian ethnicity.

PMID- 23979202
TI  - Association between baseline VEGF/sVEGFR-2 and VEGF/TSP-1 ratios and response to
      metronomic chemotherapy using cyclophosphamide and celecoxib in patients with
      advanced breast cancer.
AB  - BACKGROUND: Metronomic chemotherapy (MCT) with cyclophosphamide (Cy) and
      celecoxib (Cel) has therapeutic efficacy and low toxicity profile in advanced
      breast cancer patients (ABCP), but no reliable biomarkers of response have been
      found yet that allow patient selection for treatment. AIM: To investigate the
      potential role as biomarkers of pro- and antiangiogenic parameters and evaluate
      their response in ABCP receiving metronomic Cy 50 mg p.o./day + Cel 400 mg
      p.o./day. MATERIALS AND METHODS: Serum levels of vascular endothelial growth
      factor-C (VEGF-C), soluble VEGF receptors 2 and 3 (sVEGFR-2, sVEGFR-3), were
      measured at different time points in 13/15 patients included in a phase II trial
      of MCT with Cy+Cel. RESULTS: Serum levels of sVEGFR-2 and sVEGFR-3 increased
      significantly during treatment (P = 0.0392; P = 0.0066, respectively). VEGF-C
      showed no significant modifications. Previous determinations of VEGF and TSP-1 in
      the same patients were utilized. VEGF/sVEGFR-2, VEGF/TSP-1, and VEGF-C/sVEGFR-3
      ratios decreased significantly along the treatment (P = 0.0092; P = 0.0072; P =
      0.0141, respectively). Nonsignificant variations were observed for VEGF-C/sVEGFR
      2 ratio. Baseline values of VEGF/sVEGFR-2 and VEGF/TSP-1 ratios were associated
      with time to progression (TTP) (P = 0.0407; P = 0.0394, respectively) meanwhile
      baseline VEGF was marginally significant (P = 0.0716). Patients with values lower
      than the 50th percentile for both ratios showed longer TTP. CONCLUSIONS: We have
      identified the baseline VEGF/sVEGFR-2 and VEGF/TSP-1 ratios as potential
      biomarkers of response in ABCP treated metronomically with Cy+Cel. This finding
      warrants its confirmation in a higher number of patients.

PMID- 23979203
TI  - Efficacy and safety of metronomic administration of paclitaxel for advanced
      recurrent non-small-cell lung cancer.
AB  - CONTEXT: There are limited effective therapeutic options in the relapsed setting
      for non-small cell lung cancer (NSCLC) or in the first line for platinum
      ineligible patients. AIM: To evaluate the safety and efficacy of a metronomic
      schedule of paclitaxel administered weekly in relapsed refractory NSCLC or
      upfront in patients not eligible for platinum-based chemotherapy. SETTINGS AND
      DESIGN: Retrospective analysis of a prospectively collected database from the
      medical oncology department at Tata Memorial Hospital in Mumbai, India. MATERIALS
      AND METHODS: Patients with recurrent and treatment-naive platinum-ineligible
      advanced NSCLC were treated with weekly paclitaxel at 80 mg/m 2 with palliative
      intent. Restaging scans were obtained every two months. Chemotherapy was
      continued until progressive disease, intolerable side effects, or decision of the
      patient. STATISTICAL ANALYSIS USED: SPSS version 16 was used for analysis. Simple
      percentages were used for descriptive statistics. Progression-free survival (PFS)
      was calculated from date of start of paclitaxel till the date of progression,
      change of therapy due to any reason, or death due to any cause. Overall survival
      (OS) was calculated from date of start of paclitaxel to death. The Kaplan Meier
      method was used for estimation of survival. RESULTS: There were 37 patients over
      eight months. The median age was 59 years, with a male-to-female ratio of 5:1.
      Two patients received paclitaxel in the first line, 18 patients in second line,
      nine in third line, five in fourth line, and three were in fifth line. 73%
      patients had received prior platinum and 48.6% patients had Eastern Cooperative
      Oncology Group performance status (ECOG PS) >2. The median number of weekly
      cycles delivered was 14. The response rate was 35% [complete remission (CR):
      2.7%, partial remission (PR): 32.4%, stable disease (SD): 32.4%, progressive
      disease (PD): 27%], the median PFS was four months, and the estimated median OS
      was seven months. Chemotherapy was well tolerated. The most frequent grade 3
      toxicities included anemia: 8%, neutropenia: 5.4%, and sensory neuropathy: 8%.
      There were no grade 4 toxicities and no episodes of febrile neutropenia.
      CONCLUSIONS: Weekly low-dose continuous metronomic-type scheduling of paclitaxel
      is safe and effective for relapsed refractory NSCLC and in the first line in
      platinum-ineligible patients.

PMID- 23979204
TI  - Metronomic weekly paclitaxel in advanced unresectable esophageal cancer.
AB  - CONTEXT: Advanced esophageal cancer is aggressive with an expected median
      survival of 6-7 months. Combination chemotherapy regimens provide effective
      palliation, but result in substantial toxicity. MATERIALS AND METHODS:
      Retrospective analysis of prospectively collected data of patients with advanced
      esophageal cancer, not amenable to definitive intent therapy who were treated
      with intravenous weekly paclitaxel. RESULTS: Between October 2010 and August
      2011, 51 patients were included. Median age was 56 years, with a male: female
      ratio of 2.9:1. 29% were mid esophageal and 55% were lower third and
      gastroesophageal junction tumors. 65% of the tumors had squamous histology.
      Performance status was > 2 in 45%. 61% patients had received prior therapy,
      either definitive or palliative. 51% patients were platinum-pre-treated and 29%
      had received prior 3 weekly paclitaxel. 76% patients had distant metastases.
      Median number of cycles of weekly paclitaxel delivered was 11. 71% of patients
      had improvement in dysphagia, with a median time to symptom improvement of 9
      days. In 72% patients, the feeding nasogastric tube could be removed. Overall
      response rate was 49% (complete remission: 4%, partial remission: 45%, stable
      disease: 13%). Median progression free survival was 4.7 months (confidence
      interval [95% CI: 3.7-5.7 months]) and median overall survival was 7.5 months
      (95% CI: 3.1-11.8 months). Histopathology, performance status and pre-treatment
      albumin significantly affected survival. The most common grade 3/4 toxicities
      included hyponatremia (14%), fatigue (16%), diarrhea (12%), anemia (31%),
      neutropenia (10%) and febrile neutropenia (4%). CONCLUSIONS: Metronomic weekly
      paclitaxel chemotherapy may provide palliative benefit in advanced unresectable
      metastatic esophageal cancer with minimal toxicity.

PMID- 23979205
TI  - Oral metronomic scheduling of anticancer therapy-based treatment compared to
      existing standard of care in locally advanced oral squamous cell cancers: A
      matched-pair analysis.
AB  - CONTEXT: Head and neck cancers in developing countries present with advanced
      disease, compounded by poor access to tertiary care centers. AIM: We evaluated
      oral metronomic scheduling of anticancer therapy (MSAT) in advanced operable oral
      cancers, in conjunction with standard therapy. SETTINGS AND DESIGN: This was a
      retrospective matched-pair analysis carried out in a tertiary referral cancer
      center. MATERIALS AND METHODS: Advanced operable oral cancer patients having a
      waiting period for surgery > 3 weeks were administered MSAT. Patients then
      underwent standard therapy (surgery +/- adjuvant radiation/chemoradiation) as
      warranted by the disease, followed by MSAT maintenance therapy. Outcomes of the
      MSAT group were compared with stage-matched controls with similar waiting
      periods. STATISTICAL ANALYSIS: Survivals were found using the Kaplan-Meier method
      and compared between groups using the log rank test. RESULTS: Response was seen
      in 75% of 32 patients. Two-year disease-free survivals (DFS) in MSAT and control
      groups were 86.5 and 71.6%, respectively. Two-year DFS in MSAT group who received
      at least three months of MSAT was 94.6% (P = 0.03). CONCLUSIONS: Oral MSAT is an
      economical, effective, and safe adjuvant therapy for oral cancers. It has the
      potential for preventing progression of the disease and improving DFS.

PMID- 23979206
TI  - Metronomic therapy: chemotherapy revisited.
AB  - Cytotoxic antiproliferative chemotherapeutic agents are the mainstay of treatment
      in cancers. Chemotherapy is usually administered every 2-3 weeks. Along with
      acute toxicity and long-term effects of cumulative doses, this strategy
      potentially allows regrowth of the tumor in the interval period and leads to the
      emergence of resistant populations of tumor cells. Moreover, even with intense
      chemotherapy, the outcome is stagnating for most of the tumors. There has been
      recent interest in the use of chemotherapy in fractionated doses which is far
      below the maximum tolerated dose. This is called metronomic scheduling of
      chemotherapy. Here, we review the biology and evidence for metronomic
      chemotherapy. 

PMID- 23979207
TI  - Can combination metronomic therapy overcome chemoresistance in
      cholangiocarcinoma? A literature review.
AB  - Cholangiocarcinoma (CCa) is relatively resistant to chemotherapy as well as
      radiation therapy, and complete resection is the main curative therapy for these
      patients. The prognosis for patients with unresectable intrahepatic CCa (iCCa) is
      extremely poor. A 55-year-old woman presented at our hospital with abdominal
      pain. After evaluation, she was diagnosed to have multifocal iCCa. She did not
      opt for standard chemotherapy and therefore received oral metronomic therapy with
      a combination of celecoxib, etoposide, and cyclophosphamide for a total of 30
      months. Presently, she is 57 months post diagnosis and 27 months post cessation
      of all treatment and continues to be in complete radiological remission. In the
      present report, we review the literature and discuss whether metronomic
      scheduling of biologic agents and anticancer drugs will be able to overcome
      chemoresistance and improve the outcome in cholangiocarcinoma. References for the
      review were identified through searches of Pubmed for the last 10 years as well
      as searches of the files of the authors themselves. The final list was generated
      on the basis of originality and relevance to this review. 

PMID- 23979209
TI  - Is there a role for metronomic induction (and maintenance) therapy in elderly
      patients with acute myeloid leukemia? A literature review.
AB  - Acute myeloid leukemia (AML) in older adults differs biologically and clinically
      from that in younger patients and is characterized by adverse chromosomal
      abnormalities, stronger intrinsic resistance, and lower tolerance to
      chemotherapy. In patients over age 60 with AML, cure rates are under 10% despite
      intensive chemotherapy, and most of them die within a year of diagnosis. Over the
      last decade, metronomic chemotherapy has emerged as a potential strategy to
      control advanced/refractory cancer. Here, we report a case of a 68-year-old
      gentleman having AML with high-risk cytogenetic features, who achieved complete
      remission on our oral metronomic PrET (PrET: Prednisolone, etoposide,
      thioguanine) protocol on an outpatient basis. He was later treated with standard
      high-dose (HD) cytosine arabinoside (Ara-C) consolidation followed by maintenance
      with etoposide, thioguanine, and sodium valproate. Presently, the patient is
      nearly 35 months since diagnosis and 21 months off treatment. This case report
      and review highlights that the combination of oral low-intensity metronomic
      therapy, followed by standard HD consolidation therapy and metronomic maintenance
      therapy may be well tolerated by elderly patients especially with less
      proliferative, high (cytogenetic)-risk AML who are otherwise deemed to be unfit
      for intensive intravenous induction chemotherapy regimens. References for this
      review were identified through searches of Pubmed for recent publications on the
      subject as well as searches of the files of the authors themselves. The final
      list was generated on the basis of originality and relevance to this review. 

PMID- 23979211
TI  - My thyroid story.

PMID- 23979210
TI  - The significance of platelet consumption in the development of thrombocytopenia
      in patients with cirrhosis.
AB  - INTRODUCTION: Thrombocytopenia in cirrhosis is mainly explained by accelerated
      platelet destruction/sequestration because of hypersplenism or by decreased
      thrombopoietin levels. Excessive platelet consumption because of cirrhosis
      related hypercoagulability has also been assumed to be an etiopathologic factor
      in thrombocytopenia. To clarify whether excessive platelet consumption (eg,
      venous thrombosis and disseminated intravascular coagulation) contributes to
      thrombocytopenia in cirrhosis, the following autopsy-based study was performed.
      METHODS: Ninety-nine autopsies of chronic liver disease (80 cirrhosis and 19
      noncirrhosis) were examined retrospectively. Platelet count, weight of spleen and
      thrombotic complications were checked in autopsy protocols. Megakaryocytes in
      bone marrow were counted under high-power microscopic view. Univariate and
      multivariate analyses were performed to evaluate significances of these factors
      in thrombocytopenia. RESULTS: The platelet count was significantly lower in the
      cirrhosis cases (88 +/- 51 * 10/L) than in the noncirrhosis cases (150 +/- 120 *
      10/L). The megakaryocyte count was also lower in the cirrhosis cases (1.5 +/- 0.6
      per high-power field) than in the noncirrhosis cases (1.9 +/- 0.5 per high-power
      field). The weight of the spleen was greater in the cirrhosis cases (264 +/- 179
      g) than in the noncirrhosis cases (142 +/- 82 g). Thrombotic complications had
      been recorded in 29 cases, whose platelet count (70 +/- 41 * 10/L) was lower than
      that of those without these complications (113 +/- 80 * 10/L). Multivariate
      analysis revealed that these 3 factors (megakaryocyte count, weight of spleen,
      and thrombotic complications) were independently correlated with the platelet
      count. CONCLUSIONS: These results suggest that the imbalance of platelet
      production-destruction/sequestration-consumption contributes to thrombocytopenia
      in cirrhosis. Excessive platelet consumption cannot be ignored to explain this
      complex condition, especially in patients with major thrombotic events.

PMID- 23979212
TI  - Anticoagulation therapy: Enoxaparin dosing for VTE during pregnancy.

PMID- 23979213
TI  - Hypertension: Vitamin D supplementation lacks benefit in systolic hypertension.

PMID- 23979214
TI  - Cardiac troponin level elevations not related to acute coronary syndromes.
AB  - Over the past 2 decades, cardiac troponins (cTn) have emerged as the preferred
      biomarkers for the noninvasive detection of myocardial injury. In conjunction
      with typical clinical findings of ischaemia, elevated cTn levels in blood confirm
      a diagnosis of myocardial infarction. However, neither cTnT or cTnI are
      exclusively released as a result of ischaemic myocardial cell necrosis, but also
      with numerous nonischaemic acute and chronic cardiac conditions, such as
      myopericarditis, toxic injury, or severe cardiac overload. With the advent of
      high-sensitivity assays, causes of cTn elevation not related to an acute coronary
      syndrome (ACS) have become common findings in patients with chest pain and in
      those with acute or chronic systemic disorders. Elevated cTn levels in blood are
      associated with increased rates of cardiac events and mortality, independently of
      the underlying disease. However, the clinical conditions leading to cTn release
      in patients who do not have ACS, and the appropriate diagnostic and therapeutic
      strategies for these individuals, are largely unknown. Here, we provide an
      overview of the many causes and the prognostic importance of the release of cTn
      not related to ACS. We also recommend strategies to discriminate between
      ischaemic and nonischaemic cTn elevation, and describe the clinical evaluation of
      these patients. 

PMID- 23979217
TI  - Dyslipidaemia: Role of remnant cholesterol in IHD.

PMID- 23979215
TI  - Update on atrial fibrillation catheter ablation technologies and techniques.
AB  - Catheter ablation of atrial fibrillation (AF) has become an important treatment
      method. Electrical isolation of the pulmonary veins is the cornerstone of most AF
      ablation procedures, and is defined by an entrance block observed on a circular
      multipolar electrode catheter. The safety and efficacy of AF ablation is best
      established in middle-aged patients with paroxysmal AF. Current guidelines
      recommend AF ablation with a level Ia indication in this group of patients. The
      long-term efficacy of AF ablation is well established in patients with paroxysmal
      AF, but less so in patients with longstanding persistent AF. In this population,
      current guidelines recommend AF ablation with a level IIb indication. The
      efficacy of catheter ablation in other patient populations, particularly elderly
      people and those with concomitant conditions, is also poorly defined. AF ablation
      is reasonably effective and safe at 12 months of follow-up, but recurrence of AF
      >=1 year after ablation is not uncommon. Fortunately, the techniques and tools
      used for AF ablation continue to evolve. These developments include novel
      ablation catheters designed to increase safety, efficacy, and precision of the
      procedure, ablation strategies to target both pulmonary vein and nonpulmonary
      vein AF triggers, and improved imaging and electrical mapping to guide ablation
      procedures. 

PMID- 23979218
TI  - Social class variation in the predictors of rapid growth in infancy and obesity
      at age 3 years.
AB  - OBJECTIVE: To examine the extent to which early child nutrition, maternal
      antenatal lifestyle behaviours and child diet and lifestyle explain social class
      inequalities in the risk of rapid weight gain between birth and 3 years and
      obesity at age 3 years. DESIGN: A longitudinal and prospective birth cohort
      study. SUBJECTS: Nationally representative sample of 11,134 children and their
      parents followed from 9 months of age until 3 years. Child weight and maternal
      height and weight were measured at 9 months and 3 years and child birth weight
      was extracted from hospital records. Other predictors of child growth and obesity
      were collected by maternal report at 9 months and 3 years. RESULTS: Although born
      lighter on average, children of unskilled manual parents were 274 g heavier than
      children of professional parents by 3 years of age. The fully adjusted model of
      rapid growth from birth to 3 years of age and obesity at 3 years of age accounted
      for all social class differentials. Breastfeeding and age at the introduction of
      solids were associated with the largest average reduction (41%) in the odds ratio
      (OR) of rapid growth in the first 9 months of life for each class relative to the
      professional class. In the period from 9 months to 3 years of age, the class
      differential in rapid growth was reduced most by measures of the child's diet and
      lifestyle. However, the impact of the groups of predictors varied by social
      class. For early life growth, among the non-manual classes the proportionate
      reductions are largest when adjusted for early infant nutrition, whereas maternal
      prenatal smoking is more important for the manual social classes. CONCLUSION:
      Preventative interventions to reduce levels of childhood obesity should be multi
      dimensional but different dimensions should be given more or less significance
      depending on socio-economic group.

PMID- 23979216
TI  - Interventional cardiology in adults with congenital heart disease.
AB  - Interventional cardiac catheterization has become an integral component of the
      management of adults with congenital heart disease. The origins of this approach
      come from the paediatric interventional experience, although techniques and
      indications for interventional cardiac catheterization in adults are now being
      developed for use in the burgeoning field of adult congenital heart disease.
      Progress in the application and acceptance of interventional cardiac
      catheterization in this setting has been swift, and the pace is quickening. This
      Review provides a broad overview of some of the most common procedures used in
      the treatment of adults with congenital heart lesions, with an emphasis on new
      tools that have revolutionized the field. Specifically, we discuss interventions
      that can be broadly classified into the following groups: techniques for closing
      shunt lesions, valvular interventions, methods for achieving patency of vascular
      obstructions, and selected additional interventions applicable to some complex
      lesions. We emphasize the need for a thorough understanding of the anatomy of the
      lesion, its natural or unnatural history, and indications for intervention before
      the procedure takes place. Such procedures must be performed in centres where the
      operators are knowledgeable of the lesions being addressed, with full surgical,
      anaesthetic, nursing and imaging support. 

PMID- 23979219
TI  - Effect of endurance training on skeletal muscle myokine expression in obese men:
      identification of apelin as a novel myokine.
AB  - BACKGROUND: It has been suggested that the metabolic benefits of physical
      exercise could be mediated by myokines. We examined here the effect of exercise
      training on skeletal muscle expression of a panel of myokines in humans. Pathways
      regulating myokine expression were investigated in human myotubes. METHODS:
      Eleven obese non-diabetic male subjects were enrolled in an 8-week endurance
      training program. Insulin sensitivity was assessed by an oral glucose tolerance
      test. Subcutaneous adipose tissue and Vastus lateralis muscle biopsy samples were
      collected before and after training. RNAs were prepared from adipose tissue and
      skeletal muscle. Primary culture of myoblasts was established. RESULTS: As
      expected, exercise training improved aerobic capacity and decreased fat mass. No
      significant change in interleukin 6, fibroblast growth factor 21, myostatin
      (MSTN) or irisin mRNA level was found in muscle after training. A twofold
      increase in apelin mRNA level was found in muscle but not in adipose tissue. No
      change in circulating myokine and adipokine plasma levels was observed in the
      resting state in response to training. Interestingly, apelin was significantly
      expressed and secreted in primary human myotubes. Apelin gene expression was
      upregulated by cyclic AMP and calcium, unlike the other myokines investigated.
      Importantly, changes in muscle apelin mRNA levels were positively related to
      whole-body insulin sensitivity improvement. CONCLUSION: Collectively, our data
      show that exercise training upregulates muscle apelin expression in obese
      subjects. Apelin expression is induced by exercise signaling pathways and
      secreted in vitro in human primary myotubes, and may behave as a novel exercise
      regulated myokine with autocrine/paracrine action.

PMID- 23979220
TI  - Influence of the tolerability of vinegar as an oral source of short-chain fatty
      acids on appetite control and food intake.
AB  - BACKGROUND: Vinegar is promoted as a natural appetite suppressant, based on
      previous reports that vinegar ingestion significantly increases subsequent
      satiety. However there are concerns about the appropriateness and safety of this
      advice, and it is unclear if poor product palatability may explain previously
      published effects on appetite. OBJECTIVE: To investigate if vinegar palatability
      and tolerability have a role in suppressing appetite and food intake in two
      sequential and related acute human feeding studies. SUBJECTS AND METHODS:
      Healthy, young, normal weight unrestrained eaters were recruited to Study 1
      (n=16), an acute feeding study supplying vinegar within both palatable and
      unpalatable drinks alongside a mixed breakfast in comparison to a non-vinegar
      control; and to Study 2 (n=14), a modified sham feeding study (taste only without
      ingestion) comparing vinegar to a non-vinegar control following a milkshake
      preload. Both studies were a randomized crossover balanced design for the
      assessment of appetite, energy intake and glycaemic response. RESULTS: In Study
      1, ingestion of vinegar significantly reduced quantitative and subjective
      measures of appetite, which were accompanied by significantly higher nausea
      ratings, with unpalatable treatment having the greatest effect. Significant
      correlations between palatability ratings and appetite measures were found. In
      Study 2, orosensory stimulation with vinegar did not influence subsequent
      subjective or quantitative measures of appetite compared with control.
      CONCLUSIONS: These studies indicate that vinegar ingestion enhances satiety
      whereas orosensory stimulation alone does not, and that these effects are largely
      due to poor tolerability following ingestion invoking feelings of nausea. On this
      basis the promotion of vinegar as a natural appetite suppressant does not seem
      appropriate.

PMID- 23979221
TI  - The snacking rat as model of human obesity: effects of a free-choice high-fat
      high-sugar diet on meal patterns.
AB  - OBJECTIVES: Rats subjected to a free-choice high-fat high-sugar (fcHFHS) diet
      persistently overeat, exhibit increased food-motivated behavior and become
      overtly obese. Conversely, several studies using a non-choice (nc) high-energy
      diet showed only an initial increase in food intake with unaltered or reduced
      food-motivated behavior. This raises the question of the importance of choice in
      the persistence of hyperphagia in rats on a fcHFHS diet. SUBJECTS: Meal patterns,
      food intake and body weight gain were studied in male Wistar rats on free-choice
      diets with fat and/or sugar and in rats on nc diets with fat and sugar (custom
      made with ingredients similar to the fcHFHS diet). RESULTS: Rats on a ncHFHS diet
      initially overconsumed, but reduced intake thereafter, whereas rats on a fcHFHS
      diet remained hyperphagic. Because half of the sugar intake in the fcHFHS group
      occurred during the inactive period, we next determined whether sugar intake
      during the light phase was a necessary requirement for hyperphagia, by
      restricting access to liquid sugar to either the light or dark period with
      unlimited access to fat and chow. Results showed that hyperphagia occurred
      irrespective of the timing of sugar intake. Meal pattern analysis revealed
      consumption of larger but fewer meals in the ncHFHS group, as well as the fcHF
      group. Interestingly, meal number was increased in all rats drinking liquid sugar
      (whether on a fcHFHS or a fcHS diet), whereas a compensatory decrease in meal
      size was only observed in the fcHS group, but not the fcHFHS group. CONCLUSION:
      We hereby show the importance of choice in the observation of fcHFHS diet-induced
      hyperphagia, which results in increases in meal number due to sugar drinking
      without any compensatory decrease in meal size. We thus provide a novel dietary
      model in rats that mimics important features of human overconsumption that have
      been ignored in rodent models of obesity.

PMID- 23979222
TI  - The predictive utility of conduct disorder symptoms in preschool children: a 3
      year follow-up study.
AB  - Conduct disorder (CD) symptoms often emerge during the preschool years, but it is
      not clear whether they predict later symptoms. The present study examined whether
      age 3 CD symptoms predict age 6 CD symptoms beyond oppositional defiant disorder
      (ODD) and attention-deficit/hyperactivity disorder-hyperactive/impulsive (ADHD
      HI) symptoms. Participants were 216 preschool children (M Age  = 44.19 months),
      including an externalizing sample (n = 161) and a comparison group (n = 55).
      Parents were administered a diagnostic interview when children were 3 years old
      and again 3 years later. The externalizing sample exhibited more CD symptoms than
      the comparison sample. In the externalizing sample, initial CD symptoms predicted
      later CD symptoms above and beyond ODD and ADHD HI symptoms; this relation was
      stronger for boys than for girls. Stealing, property destruction, and fighting
      independently predicted later CD symptoms. CD symptoms also predicted subsequent
      ADHD HI symptoms and predicted ODD symptoms at a level that approached
      significance. Results support the predictive validity of CD symptoms in
      preschool. 

PMID- 23979223
TI  - B-Z transition of (dA-T)(n) duplexes induced by a spermine porphyrin-conjugate
      via an intermediate DNA conformation.
AB  - The spermine conjugate of the cationic porphyrin ligand (1) selectively induced
      the B-Z transition of the [(dA-T)n]2 sequence at low salt concentrations. The
      [(dG-C)n]2 sequence was not transformed into the Z-form. The B-Z transition was
      induced via an intermediate DNA conformation, which was formed by the external
      binding and formation of an assembly of 1 onto B-DNA.

PMID- 23979224
TI  - Clinician perspectives regarding the do-not-resuscitate order.
AB  - IMPORTANCE: While data exist regarding the frequency and timing of the do-not
      resuscitate (DNR) order in children, little is known about clinician attitudes
      and behaviors regarding this order. OBJECTIVE: To identify clinician attitudes
      regarding the meaning, implication, and timing of the DNR order for pediatric
      patients. DESIGN: Physicians and nurses from practice settings where advance care
      planning typically takes place were surveyed regarding their attitudes and
      behaviors about DNR orders. RESULTS: In total, 107 physicians and 159 nurses
      responded to the survey (N = 266). There was substantial variability in the
      interpretation of the DNR order. Most clinicians (66.9%) believe that a DNR order
      indicates limitation of resuscitative measures only on cardiopulmonary arrest. In
      reality, however, more than 85% believe that care changes beyond response to
      cardiopulmonary arrest, varying from increased attention to comfort to less
      clinician attentiveness. In addition, most clinicians reported that resuscitation
      status discussions take place later in the illness course than is ideal.
      CONCLUSIONS AND RELEVANCE: Clinicians use the DNR order not only as a guide for
      therapeutic decisions during a cardiopulmonary arrest but also as a surrogate for
      broader treatment directives. Most clinicians believe that DNR discussions should
      take place earlier than they actually do. Interventions aimed at improving
      clinician knowledge and skills in advance care discussions as well as the
      development of orders that address overall goals of care may improve care for
      children with serious illness.

PMID- 23979226
TI  - [Emergency transport and hospitalization of the elderly].

PMID- 23979227
TI  - [Prevention for the complication of gastro-intestinal tract endoscopy and
      contrast-induced nephropathy in the elderly].

PMID- 23979225
TI  - Increased sympathetic drive during the onset of hypertension in conscious Cyp1a1
      Ren2 rats.
AB  - Despite advances in our understanding concerning the pathology of hypertension,
      the mechanisms that underpin the origin of hypertension remain to be fully
      elucidated. This enigma is, at least in part, due to inherent limitations of
      various animal models of hypertension. Here, we show the genetically modified
      Cyp1a1-Ren2 rat model, in which the onset and severity of angiotensin II
      dependent hypertension can be tightly controlled, as an effective model for
      investigating increased sympathetic drive for the onset of hypertension. Cyp1a1
      Ren2 rats were surgically prepared with radiotelemetric transmitters for the
      continuous measurement of arterial blood pressure (ABP). ABP was recorded in
      freely moving rats that were fed with either normal rat chow or a diet containing
      indole-3-carbinol (0.225% w/w) for 7 days to induce hypertension. Structural
      morphology of and endothelial NO synthase (eNOS) protein expression in heart
      and/or vascular tissue were analyzed. Sympathetic tone was estimated using
      spectral analysis of heart rate variability. The progressive induction of
      hypertension over 7 days was matched with a parallel increase in sympathetic
      tone. By day 7 of hypertension, eNOS expression in the mesenteric artery was
      elevated. However, the elevated ABP, sympathetic tone, and eNOS had not elicited
      gross morphological remodeling of the heart or vasculature. Importantly, both the
      increase in sympathetic tone and overexpression of eNOS within the vasculature
      were reversed when ABP was returned to normal. We conclude that the Cyp1a1-Ren2
      rat provides an effective model for investigating specific adverse and transient
      changes in central sympathetic modulation of arterial blood pressure during the
      early onset of angiotensin-dependent hypertension.

PMID- 23979228
TI  - [Discharge planning and medical community cooperation in university hospitals].

PMID- 23979229
TI  - [Home care for the elderly].

PMID- 23979230
TI  - [The perspective of reference value -normal and abnormal in medicine].
AB  - A normal value is a laboratory parameter to discriminate between "normal" and
      "abnormal" in clinical decision-making. Because individual differences in the
      elderly are large, it can be difficult to determine a normal value as a group,
      thus reference values are basically used to assess laboratory parameters.
      However, the reference value only shows the range of average values in the
      healthy population, and does not determine or predict present and future health
      status. In geriatric practice, reference values of laboratory parameters in life
      style related disease to predict independent life is indispensable. Although
      there are many risk factors of cognitive impairment related to independent life,
      the contribution rate of each factor is small and it is often difficult to
      determine a cut-off point by conventional methods. A new methodology is required
      to determine the optimal range of clinical parameter of life-style-related
      disease using longitudinal data. 

PMID- 23979231
TI  - [The standard value of hypertension from the view of independence].

PMID- 23979232
TI  - [Life style-related disorders and independence in old patients - dyslipidemia].

PMID- 23979233
TI  - [Glycemic control in older diabetic people to prevent geriatric syndromes].

PMID- 23979234
TI  - [Metabolic syndrome and impaired daily life function in the elderly].

PMID- 23979235
TI  - [Evaluation of nutritional status of older people].

PMID- 23979236
TI  - [Locomotive syndrome: osteoarthritis].

PMID- 23979237
TI  - [Community-based medico-social network for dementia: the experience of Mitaka
      Musashino region].

PMID- 23979238
TI  - [A trial to evaluate effectiveness of development of community systems to support
      people with dementia].

PMID- 23979239
TI  - [Toward the establishment of a community-based integrated care system supporting
      the lives of elderly patients with dementia].
AB  - After reviewing the direction of the national dementia strategy from the
      perspective of the establishment of a community-based integrated care system, we
      present our recent work on strengthening medical services and promoting the early
      detection and intervention, and the integration of services for elderly patients
      with dementia. We developed a self-rating scale for assessing the capacity of
      medical facilities to provide services needed for dementia in terms of 7 latent
      factors. This scale is expected to be useful for assessing the effectiveness of
      programs aimed at strengthening medical resources, such as training programs for
      primary care physicians to increase their capacity to provide general medical
      services for patients with dementia or public programs for the establishment of a
      Medical Center for Dementia in each medical service area. We also developed an
      informant-rating scale for assessing change in behaviors affected by impairment
      of cognitive function and activities of daily living in patients with dementia,
      which had adequate reliability and validity as a screening tool for detecting
      mild dementia. The use of this scale should promote early detection,
      comprehensive geriatric assessment, access to diagnosis, care planning, and the
      integration of services for patients with dementia. 

PMID- 23979240
TI  - [Role of psychiatric care in regional collaboration on dementia].

PMID- 23979241
TI  - [Physical complications in elderly patients with advanced dementia].

PMID- 23979242
TI  - [Bone metabolism and aging].

PMID- 23979243
TI  - [The pitfall of establishment of an animal model based on cohort study and human
      bone biochemical analysis].

PMID- 23979244
TI  - [Generation of cartilaginous tissue from dermal fibroblast culture].

PMID- 23979245
TI  - [A questionnaire survey on current status of anti-diabetic therapy for diabetic
      patients with dementia].
AB  - AIM: It is important to establish treatment goals and optimal anti-diabetic
      therapy for diabetic patients with dementia. However, there are currently no
      established treatment guidelines. Recently, the West Tokyo Diabetes Association
      has established the Diabetes and Dementia Study Group to investigate the status
      of anti-diabetic therapy for diabetic patients with dementia. Here, we assessed
      the current status of such patients by a questionnaire survey. METHODS: In
      November 2011, we conducted a mailed survey to the clinics and hospitals
      affiliated with Kita-Tama, Hachioji and Tachikawa Medical Associations in Tokyo,
      Japan. The survey evaluated the most suitable anti-diabetic therapy for elderly
      diabetic patients or diabetic patients with dementia, combined anti-diabetic
      therapy, insulin therapy for elderly diabetic patients and diabetic patients with
      dementia, combination therapy of insulin and oral anti-diabetic agents for
      diabetic patients with dementia, factors that make it difficult for diabetic
      patients with dementia to continue insulin therapy, and selection of treatment or
      care for diabetic patients with dementia. RESULTS: The responses indicated that
      the anti-diabetic agents appropriate for diabetic patients with dementia are
      dipeptidyl peptidase-4 inhibitors. Those inappropriate for the same patients are
      metformin and insulin. Family support was a major factor for insulin therapy
      continuation for diabetic patients with dementia. Moreover, anti-diabetic agents
      for these patients are selected according to their ease of use and compatibility
      with available familial and social resources. CONCLUSION: Our survey results can
      be utilized for the creation of new guidelines and educational resources for the
      anti-diabetic therapy of diabetic patients with dementia.

PMID- 23979246
TI  - [Incidence and clinical outcome of contrast-induced nephropathy in the elderly
      patients].
AB  - BACKGROUND: Aging is an established risk factor for contrast-induced nephropathy
      (CIN). However, little information is available on the incidence and clinical
      outcome of CIN for the elderly patients in Japan. OBJECTIVES: We determined the
      incidence and clinical outcome of CIN in the Japanese elderly patient. METHODS:
      We studied 292 patients who had mild renal dysfunction (estimated glomerular
      filtration rate (eGFR) <60 ml/min/1.73 m(2)) at baseline and underwent coronary
      angiography. Patients were divided into two groups base on their age: the elderly
      group (age >= 75, n=108) and the control group (age<75, n=184). CIN was defined
      as a 25% increase in serum creatinine or an increase in serum creatinine by>0.5
      mg/dl above the baseline value at or within 2 days post procedure. RESULTS:
      Patients in the elderly group had a higher incidence of CIN (14%) than those in
      the control group (9%). In patients who developed CIN, there was no significant
      difference between the two groups in baseline GFR and GFR on days 1, 2, 7 and 30
      after the procedure. However, the relative increase in GFR above baseline on day
      7 (-4.0 +/- 6.1 vs -8.3 +/- 8.0 ml/min P=0.096) and day 30 (1.5 +/- 9.4 vs -10.1
      +/- 9.6 ml/min P=0.0017) in the elderly group was higher than that in the control
      group. Furthermore, death occurred in 3 patients in the elderly group (20%)
      whereas no patient died in the control group (P=0.092). CONCLUSION: Aging (age >=
      75) is a risk factor for CIN in Japanese. CIN in the elderly patients may be
      associated with prolonged renal dysfunction and poor prognosis.

PMID- 23979247
TI  - [Establishment of a short-form screening test for malnutrition in a newly
      developed comprehensive geriatric assessment initiative named 'Dr. SUPERMAN'].
AB  - AIM: Assessment of the nutritional state is important in comprehensive geriatric
      assessment (CGA). Several standardized screening tests for malnutrition are
      available such as the Mini-Nutritional Assessment (MNA) and MNA-Short Form (MNA
      SF). However, it takes more than 10 minutes to perform the MNA-SF alone. We have
      developed a CGA initiative named 'Dr. SUPERMAN', which is designed to accomplish
      CGA within 10 minutes. In this study, we evaluated a short-form screening test
      for malnutrition preceding the MNA. METHODS: The MNA-SF, which consists of 6
      items (A-F), was administered to 163 elderly outpatients (mean age: 83.4 years,
      80 men) with various diseases. Using the results of the MNA-SF score (normal >=
      12 and abnormal <= 11) as a gold standard, the sensitivity, specificity, and
      positive predictive values (PPVs) of each item were calculated and the best
      combination of 2 items for identifying malnutrition among the elderly outpatients
      was selected. According to the combination of 2 items (item B: weight loss during
      the last 3 months; item F: body mass index (BMI)/calf circumference (CC) in cm),
      they were divided into 2 groups: the normal control (NC) group (neither items B
      nor F) and the malnutrition/at risk (MN) group (either items B or D, or both).
      Findings of the clinical feature, anthropometric measurement, and nutritional
      biomarker between the 2 groups were examined to clarify the characteristics of
      each. RESULTS: The MNA-SF score was distributed as follows: 3-7 in 12 cases, 8-11
      in 68 cases, and 12-14 in 83 cases. Based on the MNA-SF score, the combination of
      items B and F revealed the highest sensitivity (91.3%), specificity (63.9%), and
      PPV (70.9%), resulting in 103 cases in the MN group and 60 cases in the NC group.
      A high frequency of anorexia, living alone, hypoprealbuminemia, lymphocytopenia,
      and dehydration was observed in the MN group, whereas a high frequency of leg
      edema was observed in the NC group. Cases showing a positive wall-occiput test,
      which compelled the alternation of CC with BMI, accounted for 24% of all cases.
      CONCLUSIONS: The combination of 'weight loss during the last 3 months' and
      initial BMI >= 23/CC <31 cm along with a positive wall-occiput test was a useful
      and valuable SF screening test for malnutrition in elderly outpatients.

PMID- 23979248
TI  - [Classification of reduced sense of smell in women with Parkinson's disease].
AB  - AIM: It is well known that patients with Parkinson's disease (PD) prominently
      experience difficulty in smelling, a nonmotor symptom, without any signs or
      symptoms from an early stage. However, no study on the classification of the
      reduced sense of smell has been performed. We compared the classification of
      reduced sense of smell (bromine) between PD patients and healthy subjects to
      clarify the disorder profile. METHODS: The subjects were 14 female neurology
      outpatients clinically diagnosed with PD (mean age: 71.6 +/- 6.1 years) and 11
      female elderly healthy subjects without any psychiatric or neurological disorders
      (mean age: 68.9 +/- 6.9 years). In this study, the Japanese odor stick
      identification test was used. RESULTS: Both the PD patients and the healthy
      subjects showed a reduced sense of smell for the bromine of lumber, orange, and
      domestic gas. The PD patients preserved a sense of smell for perfume, but they
      showed a significantly lower sense of smell than the healthy subjects for the
      bromine of China ink, menthol, curry, rose, cypress, sweaty socks, and condensed
      milk; this indicates that bromine can be a supportive diagnostic index for PD.
      CONCLUSION: It was considered important to evaluate the reduced sense of smell in
      PD patients to avoid hazards in their daily lives and to conduct an effective
      rehabilitation program.

PMID- 23979249
TI  - [Screening test for overactive bladder in a newly developed comprehensive
      geriatric assessment initiative].
AB  - PURPOSE: Lower urinary tract symptoms, particularly in overactive bladder (OAB),
      are frequently observed among elderly patients. The impact of OAB on their
      quality of life is so strong that the assessment of OAB is necessary in
      comprehensive geriatric assessment (CGA). As CGA takes time to complete, we
      established a convenient instrument consisting of 2 questions on OAB and assessed
      its utility. METHOD: We recruited 123 elderly patients with various diseases
      (mean age: 83.2 years, 63 men), in whom 2 questions on nocturia (Q1) and urinary
      incontinence at night (Q2) were asked. Thereafter, overactive bladder symptom
      scores (OABSS) were obtained to diagnose OAB based on the OAB criteria.
      Statistical analyses for Q1 and Q2 were performed using the OABSS criterion as a
      gold standard. To elucidate the clinical characteristics of the elderly patients,
      they were divided into 2 groups on the basis of the presence or absence of
      nocturia: nocturia (+) and nocturia (-) groups. The nocturia (+) group was
      subdivided into 2 subgroups: with or without incontinence. RESULTS: Nocturia (Q1)
      was observed in 82 elderly patients and urinary incontinence (Q2) in 23, whereas
      OAB was diagnosed in 22. The sensitivity, specificity, and positive predictive
      value (PPV) of Q1 (Q1+Q2) were 100% (68.2%), 40.6% (92.1%), and 26.8% (65.2%),
      respectively. The nocturia (+) group patients were characterized as predominantly
      composed of men with cerebrovascular disease, disturbed activities of daily
      living, interrupted sleep, delayed wake-up time, and treatment with diuretics.
      Furthermore, Parkinson disease, depressive state, sedentary life style, and
      treatment without diuretics were frequently observed in patients in the
      incontinence (+) subgroup. CONCLUSION: A low PPV with a high sensitivity of Q1
      was improved by using Q1+Q2, where both Q1 and Q2 enable better assessment of OAB
      resulting in being a useful screening test for OAB.

PMID- 23979250
TI  - [Oral diadochokinesis among Japanese aged over 55 years: analysis of standard
      values].
AB  - AIM: We investigated oral diadochokinesis (OD) among 212 Japanese aged over 55
      years to assess the standard values of articulation ability. METHODS: Each
      subject repeatedly produced the OD syllables /pa/, /ta/, and /ka/. Subjects were
      divided into three age-groups (55-64 years, 65-74 years, and over 75 years) and
      by gender to compare the number of OD syllables per second. We also calculated
      the lower limit of values that determined the standard range for OD syllables.
      RESULTS: The number of all OD syllables in the over-75 age-group was
      significantly lower than in the 55-64 group. The number of OD /pa/ syllables in
      the over-75 group was significantly lower than in the 65-74 group. The number of
      OD /ta/ syllables in the 65-74 group was significantly lower than in the 55-64
      group. The lower limit of the standard values for OD /pa/, /ta/, and /ka/ was,
      respectively, as follows: 4.9, 4.7, and 4.5 times in the 55-64 group; 3.8, 4.1,
      and 3.7 times in the 65-74 group; and 3.8, 3.3, and 2.6 times in the over-75
      group. Among women, the number of OD /pa /, /ta/, and /ka/ syllables was
      significantly lower in the over-75 group than in other age-groups. CONCLUSIONS:
      We demonstrated that the lower limit of standard OD values is a means of
      assessing articulation in elderly subjects. We found that OD /ta/ tends to
      decrease from age 65 years. The decline in articulation ability clearly begins
      earlier in women than in men.

PMID- 23979251
TI  - [Ear cleaning and comprehensive geriatric assessment in Japanese elderly].

PMID- 23979252
TI  - [Simple screening test using instrumental activities of daily living to find
      early stage of dementia].

PMID- 23979253
TI  - [Nature and ability of managers of long-term care health facilities].

PMID- 23979254
TI  - Solution-phase synthesis of single-crystal Cu3Si nanowire arrays on diverse
      substrates with dual functions as high-performance field emitters and efficient
      anti-reflective layers.
AB  - There is strong and growing interest in applying metal silicide nanowires as
      building blocks for a new class of silicide-based applications, including
      spintronics, nano-scale interconnects, thermoelectronics, and anti-reflective
      coating materials. Solution-phase environments provide versatile materials
      chemistry as well as significantly lower production costs compared to gas-phase
      synthesis. However, solution-phase synthesis of silicide nanowires remains
      challenging due to the lack of fundamental understanding of silicidation
      reactions. In this study, single-crystalline Cu3Si nanowire arrays were
      synthesized in an organic solvent. Self-catalyzed, dense single-crystalline Cu3Si
      nanowire arrays were synthesized by thermal decomposition of monophenylsilane in
      the presence of copper films or copper substrates at 420 to 475  degrees C and
      10.3 MPa in supercritical benzene. The solution-grown Cu3Si nanowire arrays serve
      dual functions as field emitters and anti-reflective layers, which are reported
      on copper silicide materials for the first time. Cu3Si nanowires exhibit superior
      field-emission properties, with a turn-on-voltage as low as 1.16 V MUm(-1), an
      emission current density of 8 mA cm(-2) at 4.9 V MUm(-1), and a field enhancement
      factor (beta) of 1500. Cu3Si nanowire arrays appear black with optical absorption
      less than 5% between 400 and 800 nm with minimal reflectance, serving as highly
      efficient anti-reflective layers. Moreover, the Cu3Si nanowires could be grown on
      either rigid or flexible substrates (PI). This study shows that solution-phase
      silicide reactions are adaptable for high-quality silicide nanowire growth and
      demonstrates their promise towards fabrication of metal silicide-based devices. 

PMID- 23979255
TI  - A laser-induced mouse model of chronic ocular hypertension to characterize visual
      defects.
AB  - Glaucoma, frequently associated with elevated intraocular pressure (IOP), is one
      of the leading causes of blindness. We sought to establish a mouse model of
      ocular hypertension to mimic human high-tension glaucoma. Here laser illumination
      is applied to the corneal limbus to photocoagulate the aqueous outflow, inducing
      angle closure. The changes of IOP are monitored using a rebound tonometer before
      and after the laser treatment. An optomotor behavioral test is used to measure
      corresponding changes in visual capacity. The representative result from one
      mouse which developed sustained IOP elevation after laser illumination is shown.
      A decreased visual acuity and contrast sensitivity is observed in this ocular
      hypertensive mouse. Together, our study introduces a valuable model system to
      investigate neuronal degeneration and the underlying molecular mechanisms in
      glaucomatous mice.

PMID- 23979256
TI  - Acceleration bias in visually perceived velocity change and effects of
      Parkinson's bradykinesia.
AB  - In Parkinson's disease (PD), basal ganglia dysfunction leads to disturbed
      sensorimotor integration and associated timing. Previous functional MRI and
      behavioural PD studies on timing indicated a specific striatal contribution to
      assessing spatial displacement in velocity estimation. In this computation,
      cerebral processing time implies demarcating discrete intervals of spatial
      change. To quantify these putative intervals, the threshold of perceived velocity
      change of a moving ball was assessed in healthy volunteers and PD patients. After
      rebound from the upper side of a monitor screen, the ball's velocity increased or
      decreased with variable magnitudes while participants indicated whether they
      noticed this velocity change. The threshold for detecting velocity change was
      around 0.014 rad/s in both groups. Moreover, velocity was perceived as equal when
      the ball decelerated; unchanged velocity was perceived as acceleration. This
      shift was 0.009 rad/s for healthy volunteers and 0.007 rad/s for PD patients, and
      was negatively correlated with the severity of bradykinesia. As the trajectory
      length before and after velocity change was the same, velocity change was also
      expressed as a change in stimulus duration (relative to 1 s initial duration).
      The temporal equivalent of a threshold for perceived velocity change was around
      75 ms in both groups. The perceptual 'acceleration bias' is in line with the
      'flash-lag' effect: the position of a moving stimulus is projected ahead compared
      with a stationary landmark. Such an extrapolation over adjacent past and
      predicted locations enables 'real-time' visuomotor control, notwithstanding
      delays because of intrinsic cerebral processing time. In PD, such impaired
      perceptual feed-forward processing may result in slow movements. 

PMID- 23979257
TI  - Cerebral uptake and protein incorporation of cyanobacterial toxin beta-N
      methylamino-L-alanine.
AB  - beta-N-methylamino-L-alanine (BMAA) is a nonprotein amino acid produced by
      diverse species of free-living cyanobacteria found in terrestrial and aquatic
      environments worldwide. BMAA has been detected as a soluble (free) and insoluble
      protein-bound (bound) amino acid in brains of Alzheimer's disease, amyotrophic
      lateral sclerosis, and Guamanian amyotrophic lateral sclerosis/Parkinsonism
      dementia complex patients. A toxic reservoir of BMAA in the brain may be
      excitotoxic to neurons or serve to disrupt cerebral protein homeostasis. Here, we
      report tracer uptake kinetics and a time course for protein incorporation of [C]
      L-BMAA into the brain of C57/BL6 mice. BMAA pharmacokinetic parameters measured
      in plasma show a rapid distribution phase and a terminal elimination half-life of
      1.7 days following bolus intravenous administration. Total [C]-L-BMAA uptake to
      the brain reached a maximum at 1.5 h. Ex-vivo autoradiography of [C]-labeled BMAA
      showed dense labeling within the ventricles, choroid plexus, and whole-brain gray
      matter structures. Radioactivity measured in soluble and trichloroacetic acid
      precipitates was compared to determine the incorporation of [C]-L-BMAA into total
      brain protein. The maximal concentration of [C]-L-BMAA was measured in protein
      bound fractions of brain at 4 h, followed by a corresponding decrease in the free
      pool of this nonprotein amino acid. The time-dependent association of [C]-L-BMAA
      in the protein-bound fraction suggests that BMAA may be trapped in new proteins
      by protein synthesis-dependent processes. BMAA may accumulate into growing
      polypeptide chains and recycle to the free pool with protein turnover. 

PMID- 23979258
TI  - Brain activity evoked by motor inhibition before volitional finger movement.
AB  - The present study investigated the brain activity that accompanied motor
      inhibition before movement in human volitional finger movement. Seven individuals
      were instructed to press a force sensor with the right index finger. The time to
      begin this movement was indicated with a clock making a 4-s revolution. The time
      at which the clock hand passed the 3 o'clock position was adopted as the go
      signal in the go task. In the series of trials, the task, we designated as
      prestop task, was performed with a red light-emitting diode stop-signal presented
      randomly at 0.1, 0.2, 0.3, 0.4, or 0.5 s before the go-signal. Cerebral
      potentials from the scalp were recorded using a 20-channel electroencephalography
      system. In the go task without the stop-signal, clear movement-related cortical
      potentials were observed. In the prestop tasks with the stop-signal, the
      participants were able to inhibit finger movement. A positive
      electroencephalography potential distributed at the midline frontocentral scalp
      400 ms after the stop-signal was observed only in the prestop task. This suggests
      that the observed positive component is associated with the interruption of motor
      intent, as well as the revision of motor planning, in the motor cortices before
      the movement. 

PMID- 23979259
TI  - Role of the dorsolateral prefrontal cortex in recognizing hand actions performed
      in social contexts: a functional MRI study.
AB  - We investigated the role of the prefrontal areas in recognizing hand actions
      performed in social contexts. We used video clips depicting the interaction
      between two individuals: one person (requester) requested the other person to
      pass one of two objects. The other person (responder) then passed the object that
      was congruent to the request in the congruent condition or incongruent in the
      incongruent condition. Both requester and responder appeared on screen in the two
      person condition and only the responder appeared in the one-person condition.
      Participants were required to observe the clips and to judge whether the
      responder's actions were congruent or incongruent. Functional MRI showed the
      incongruency effect in the prefrontal cortex. In particular, the brain areas
      including the bilateral dorsolateral prefrontal cortex showed the interaction
      effect; the magnitude of activation in the incongruent condition was
      significantly higher than that in the congruent condition, but this difference
      was found only in the two-person condition. These results suggest that the
      dorsolateral prefrontal cortex play an important role in the detection of
      incongruency between the requester's request and the responder's action depending
      on social contexts. 

PMID- 23979260
TI  - The stereochemistry of amide side chains containing carboxyl groups influences
      water exchange rates in EuDOTA-tetraamide complexes.
AB  - Many Eu(III) complexes formed with DOTA-tetraamide ligands (where DOTA is
      1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) have sufficiently slow
      water exchange kinetics to meet the slow-to-intermediate condition required to
      serve as chemical exchange saturation transfer (CEST) contrast agents for MRI.
      This class of MRI contrast agents offers an attractive platform for creating
      biological sensors because water exchange is exquisitely sensitive to subtle
      ligand stereochemistry and electronic effects. Introduction of carboxyl groups or
      carboxyl ethyl ester groups on the amide substituents has been shown to slow
      water exchange in these complexes, but less is known about the orientation or
      position of these side-chain groups relative to the inner-sphere Eu(III)-bound
      water molecule. In this study, a series of Eu(III) complexes having one or more
      carboxyl groups or carboxyl esters at the delta-position of the pendant amide
      side chains were prepared. Initial attempts to prepare optically pure EuDOTA-[(S)
      Asp]4 resulted in a chemically pure ligand consisting of a mixture of
      stereochemical isomers. This was traced to racemization of (S)-aspartate diethyl
      ester during the synthetic procedure. Nevertheless, NMR studies of the Eu(III)
      complexes of this mixture revealed that each isomer had a different water
      exchange rate, differing by a factor of 2 or more. A second controlled synthesis
      and CEST study of EuDOTA-[(S)-Asp]4 and cis-EuDOTA-[(S)-Asp]2[(R)-Asp]2 confirmed
      that the water exchange rates in these diastereomeric complexes are controlled by
      the axial versus equatorial orientation of the carboxyl groups on the amide side
      chains. These observations provide new insights toward the development of even
      more slowly water exchanging systems which will be necessary for practical in
      vivo applications.

PMID- 23979261
TI  - Evolution of plant mitochondrial intron-encoded maturases: frequent lineage
      specific loss and recurrent intracellular transfer to the nucleus.
AB  - Among land plants, mitochondrial and plastid group II introns occasionally encode
      proteins called maturases that are important for splicing. Angiosperm nuclear
      genomes also encode maturases that are targeted to the organelles, but it is not
      known whether nucleus-encoded maturases exist in other land plant lineages. To
      examine the evolutionary diversity and history of this essential gene family, we
      searched for maturase homologs in recently sequenced nuclear and mitochondrial
      genomes from diverse land plants. We found that maturase content in mitochondrial
      genomes is highly lineage specific, such that orthologous maturases are rarely
      shared among major land plant groups. The presence of numerous mitochondrial
      pseudogenes in the mitochondrial genomes of several species implies that the
      sporadic maturase distribution is due to frequent inactivation and eventual loss
      over time. We also identified multiple maturase paralogs in the nuclear genomes
      of the lycophyte Selaginella moellendorffii, the moss Physcomitrella patens, and
      the representative angiosperm Vitis vinifera. Phylogenetic analyses of organelle-
      and nucleus-encoded maturases revealed that the nuclear maturase genes in
      angiosperms, lycophytes, and mosses arose by multiple shared and independent
      transfers of mitochondrial paralogs to the nuclear genome during land plant
      evolution. These findings indicate that plant mitochondrial maturases have
      experienced a surprisingly dynamic history due to a complex interaction of
      multiple evolutionary forces that affect the rates of maturase gain, retention,
      and loss.

PMID- 23979263
TI  - Opportunity costs associated with caring for older Mexican-Americans.
AB  - Long-term care use among older Mexican-Americans is poorly understood, despite
      the adverse effects on health and economic disadvantage in this vulnerable
      population. This study examines gender-based risk of long-term care use in 628
      women and 391 men, age 70 and over in the 2000-2001 and 2004-2005 waves of the
      Hispanic Established Populations for Epidemiologic Studies of the Elderly.
      Logistic regression models are employed to assess the impact of the opportunity
      cost implications of family support (kin availability and co-residence) relative
      to health care needs (quality-adjusted life years (QALY) weighted scores and
      functional limitations) on women's risk of entry into a nursing home. A small
      percentage (~5%) of men and women had entered a long-term care facility. Women
      had lower weights for QALY weights and greater disability than men, but on
      average were more likely to live with or in closer proximity to an adult child.
      Higher disability rates (p < 0.01) increased the risk of institutionalization
      regardless of gender because disability increases time burdens. Families with
      fewer adult children faced higher time burdens per child in caring for elderly
      parents; particularly for elderly mothers. Demographic trends suggest that the
      number of adult children available to share the caregiving load may decrease long
      term care use.

PMID- 23979262
TI  - Evolution of cyclic amidohydrolases: a highly diversified superfamily.
AB  - Dihydroorotases are universal proteins catalyzing the third step of pyrimidine
      biosynthesis. These zinc metalloenzymes belong to the superfamily of cyclic
      amidohydrolases, comprising also other enzymes that are involved in degradation
      of either purines (allantoinases), pyrimidines (dihydropyrimidinases) or
      hydantoins (hydantoinases). The evolutionary relationships between these
      mechanistically related enzymes were estimated after designing a method to build
      an accurate multiple sequence alignment. The amino acid sequences that have been
      crystallized were used to build a seed alignment. All the remaining homologues
      were progressively added by aligning their HMM profiles to the seed HMM profile,
      allowing to obtain a reliable phylogeny of the superfamily. This helped us to
      propose a new evolutionary classification of dihydroorotases into three major
      types, while at the same time disentangling an important part of the history of
      their complex structure-function relationships. Although differing in their
      substrate specificity, allantoinases, hydantoinases and dihydropyrimidinases are
      found to be phylogenetically closer to DHOase Type I than the proximity of the
      three DHOase types to each other. This suggests that the primordial cyclic
      amidohydrolase was a multifunctional, highly evolvable generalist, with high
      conformational diversity allowing for promiscuous activities. Then, successive
      gene duplications allowed resolving the primordial substrate ambiguity in various
      substrate specificities. The present-day superfamily of cyclic amidohydrolases is
      the result of the progressive divergence of these ancestral paralogous copies by
      descent with modification. 

PMID- 23979264
TI  - Gender differences in factors influencing electrocardiographic findings of left
      ventricular hypertrophy in severe aortic stenosis.
AB  - We investigated gender differences in factors influencing the
      electrocardiographic (ECG) findings of left ventricular hypertrophy (LVH) in
      patients with severe aortic stenosis (AS). The functional and geometric responses
      of the left ventricle to chronic pressure overload, such as hypertension and AS,
      have been reported to be different between men and women. However, gender
      differences in the factors influencing the ECG findings of LVH in pressure
      overload remain unknown. We conducted a retrospective observational study in
      consecutive patients with severe AS (aortic valve area (AVA) assessed by cardiac
      catheterization <1.0 cm(2)) without concomitant significant aortic regurgitation,
      mitral stenosis and/or regurgitation, conduction disturbance, or myocardial
      infarction (n = 35 males, 68 females). The ECG criteria were classified into
      three categories: (1) high voltage by the Sokolow-Lyon index associated with ST-T
      wave changes (with no digitalis therapy); (2) high voltage alone; and (3) normal.
      Groups 1 and 2 were defined as LVH on ECG. We compared the ECG findings in
      relation to the AS severity between genders. Women were older, but there were no
      significant differences in the prevalence of hypertension, AVA index (AVAI), mean
      pressure gradient or peak velocity across the AV, LV mass index (LVMI) derived
      from echocardiography or the distribution of ECG categories between genders. A
      multiple logistic regression analysis including age, gender, hypertension, AVAI,
      mean pressure gradient, and LVMI revealed that the LVMI (P = 0.001) and AVAI (P =
      0.0434) were significantly related to the distribution of ECG categories. LVMI
      significantly predicted LVH on ECG in both genders, but AVAI was a predictive
      factor in only women. ECG LVH in patients with severe AS may be mainly reflected
      by LVMI in men and by both LVMI and AVAI in women. Factors other than AVA, such
      as end-stage disease and/or complicating factors such as hypertension, may
      underlie the observed differences in ECG findings of LVH between men and women.

PMID- 23979265
TI  - Pentraxin 3 is a local inflammatory marker in atrial fibrillation.
AB  - Increasing evidence indicates that inflammation contributes to the pathogenesis
      of atrial fibrillation (AF). Pentraxin 3 (PTX3) is produced abundantly in local
      inflammatory lesions while C-reactive protein (CRP) is produced mainly in the
      liver. In this study, we investigated whether a local level of PTX3 might be a
      sensitive marker for the local inflammation of AF. Blood from the periphery and
      left atrial appendage (LAA) was sampled from 23 patients with AF undergoing
      pulmonary vein isolation, and from 10 control subjects with Wolff-Parkinson-White
      syndrome. We measured peripheral and LAA plasma concentrations of CRP,
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and PTX3. Plasma
      PTX3 concentrations in both locations were higher in patients with AF than in
      control subjects. PTX3 concentrations were significantly higher in the LAA than
      the periphery in patients with AF (3.7 +/- 1.4 vs 3.3 +/- 1.2 ng/ml, P < 0.01),
      but not in control subjects (2.4 +/- 0.5 vs 2.4 +/- 0.5 ng/ml, not significant).
      Patients and controls showed no significant differences in CRP, IL-6, or TNF
      alpha concentrations between the periphery and LAA. Interestingly, there was a
      significant positive correlation between LAA plasma concentrations of PTX3 and
      left atrial volume (r = 0.55, P < 0.01). These data demonstrate that local PTX3
      production in the left atrium might reflect the local inflammation of AF.

PMID- 23979267
TI  - A randomized controlled pilot trial of modified whole blood versus component
      therapy in severely injured patients requiring large volume transfusions.
AB  - OBJECTIVES: To determine whether resuscitation of severely injured patients with
      modified whole blood (mWB) resulted in fewer overall transfusions compared with
      component (COMP) therapy. BACKGROUND: For decades, whole blood (WB) was the
      primary product for resuscitating patients in hemorrhagic shock. After dramatic
      advances in blood banking in the 1970s, blood donor centers began supplying
      hospitals with individual components [red blood cell (RBC), plasma, platelets]
      and removed WB as an available product. However, no studies of efficacy or
      hemostatic potential in trauma patients were performed before doing so. METHODS:
      Single-center, randomized trial of severely injured patients predicted to large
      transfusion volume. Pregnant patients, prisoners, those younger than 18 years or
      with more than 20% total body surface area burns (TBSA) burns were excluded.
      Patients were randomized to mWB (1 U mWB) or COMP therapy (1 U RBC+ 1 U plasma)
      immediately on arrival. Each group also received 1 U platelets (apheresis or
      prepooled random donor) for every 6 U of mWB or 6 U of RBC + 6 U plasma. The
      study was performed under the Exception From Informed Consent (Food and Drug
      Administration 21 code of federal regulations [CFR] 50.24). Primary outcome was
      24-hour transfusion volumes. RESULTS: A total of 107 patients were randomized (55
      mWB, 52 COMP therapy) over 14 months. There were no differences in demographics,
      arrival vitals or laboratory values, injury severity, or mechanism. Transfusions
      were similar between groups (intent-to-treat analysis). However, when excluding
      patients with severe brain injury (sensitivity analysis), WB group received less
      24-hour RBC (median 3 vs 6, P = 0.02), plasma (4 vs 6, P = 0.02), platelets (0 vs
      3, P = 0.09), and total products (11 vs 16, P = 0.02). CONCLUSIONS: Compared with
      COMP therapy, WB did not reduce transfusion volumes in severely injured patients
      predicted to receive massive transfusion. However, in the sensitivity analysis
      (patients without severe brain injuries), use of mWB significantly reduced
      transfusion volumes, achieving the prespecified endpoint of this initial pilot
      study.

PMID- 23979268
TI  - A risk prediction model for determining appropriateness of CEA in patients with
      asymptomatic carotid artery stenosis.
AB  - OBJECTIVE: The benefit of carotid endarterectomy (CEA) over medical therapy in
      patients with asymptomatic carotid artery stenosis is predicated upon a life
      expectancy of at least 5 years after the procedure. The goal of this study was to
      create a scoring system for prediction of 5-year survival after CEA that can be
      used to triage patients with ACAS. METHODS: All patients who underwent CEA for
      severe asymptomatic carotid stenosis from 1989 to 2005 were identified. Long-term
      survival was determined by a review of hospital records and the social security
      death index. Because all patients had at least 5-year follow-up, a logistic
      regression of predictors of survival at 5 years was performed and the odds ratios
      associated with particular significant comorbidities were used to create a
      scoring system to predict survival. The scoring system was then validated within
      the cohort using the Hosmer-Lemeshow Test and a derivation/validation receiver
      operating characteristic (ROC) curve. RESULTS: There were 2004 CEA performed in
      1791 patients. The average follow-up was 130 +/- 49 months. The clinical profile
      of the cohort data included 84% hypertension, 56% coronary artery disease (CAD),
      24% diabetes, and 71% on statins. The 30-day stroke rate was 1.1% and the death
      rate was 0.7%. The actual 5-year survival was 73%. Logistic regression yielded
      the following predictors of mortality: age (by decade) (odds ratio [OR] = 1.8, P
      < 0.0001), CAD (OR = 1.5, P = 0.0007), chronic obstructive pulmonary disease (OR
      = 2.5; P < 0.0001), diabetes (OR = 1.7, P < 0.0001), neck radiation (OR = 2.6, P
      = 0.005), no statin (OR = 2.1, P < 0.0001), and creatinine more than 1.5 (OR =
      2.6, P < 0.0001). These variables were then assigned a hierarchal point scoring
      system in accordance with the OR value. The 5-year survival based on the scoring
      system was as follows: 0 to 5 points = 92.5%, 6 to 8 points = 83.6%, 9 to 11
      points = 63.7%, 12 to 14 points = 46.5%, and more than 15 points = 33.8%. The
      Hosmer-Lemeshow test validated the scoring system (P = 0.26) and there was no
      difference in the ROC curves (C statistic = 0.74 vs 0.73). CONCLUSIONS: This
      validated scoring system can be a useful tool for determining which patients are
      likely to benefit most from CEA based on the probability of long-term survival.
      Given that the 5-year survival of patients in the medical arm of the asymptomatic
      CEA trials was 60% to 70%, it is reasonable to conclude that patients who score 0
      to 8 points are excellent candidates for CEA whereas most patients with >=12
      points should be managed with medical therapy alone.

PMID- 23979266
TI  - Fluvastatin-induced reduction of oxidative stress ameliorates diabetic
      cardiomyopathy in association with improving coronary microvasculature.
AB  - Diabetic cardiomyopathy is associated with increased oxidative stress and
      vascular endothelial dysfunction, which lead to coronary microangiopathy. We
      tested whether statin-induced redox imbalance improvements could ameliorate
      diabetic cardiomyopathy and improve coronary microvasculature in streptozotocin
      induced diabetes mellitus (DM). Fluvastatin (10 mg/kg/day) or vehicle was orally
      administered for 12 weeks to rats with or without DM. Myocardial oxidative stress
      was assessed by NADPH (nicotinamide adenine dinucleotide phosphate) oxidase
      subunit p22(phox) and gp91(phox) mRNA expression, and myocardial 8-iso
      prostaglandin F(2alpha) (PGF(2alpha)) levels. Myocardial vascular densities were
      assessed using anti-CD31 and anti-alpha-smooth muscle actin (SMA) antibodies.
      Fluvastatin did not affect blood pressure or plasma cholesterol, but attenuated
      increased left ventricular (LV) minimum pressure and ameliorated LV systolic
      dysfunction in DM rats in comparison with vehicle (LV dP/dt, 8.9 +/- 1.8 vs 5.4
      +/- 1.0 * 10(3) mmHg/s, P < 0.05). Myocardial oxidative stress increased in DM,
      but fluvastatin significantly reduced p22(phox) and gp91(phox) mRNA expression
      and myocardial PGF(2alpha) levels. Fluvastatin enhanced myocardial endothelial
      nitric oxide synthase (eNOS) protein levels and increased eNOS, vascular
      endothelial growth factor, and hypoxia-inducible factor-1alpha mRNA expression.
      CD31-positive cell densities were lower in DM rats than in non-DM rats (28.4 +/-
      13.2 vs 48.6 +/- 4.3/field, P < 0.05) and fluvastatin restored the number (57.8
      +/- 18.3/field), although there were no significant differences in SMA-positive
      cell densities between groups. Fluvastatin did not affect cardiac function,
      oxidative stress, or vessel densities in non-DM rats. These results suggest that
      beneficial effects of fluvastatin on diabetic cardiomyopathy might result, at
      least in part, from improving coronary microvasculature through reduction in
      myocardial oxidative stress and upregulation of angiogenic factor.

PMID- 23979269
TI  - The cost of obesity for nonbariatric inpatient operative procedures in the United
      States: national cost estimates obese versus nonobese patients.
AB  - OBJECTIVE: To evaluate the economic impact of obesity on hospital costs
      associated with the commonest nonbariatric, nonobstetrical surgical procedures.
      BACKGROUND: Health care costs and obesity are both rising. Nonsurgical costs
      associated with obesity are well documented but surgical costs are not. METHODS:
      National cost estimates were calculated from the Healthcare Cost and Utilization
      Project (HCUP) Nationwide Inpatient Sample (NIS) database, 2005-2009, for the
      highest volume nonbariatric nonobstetric procedures. Obesity was identified from
      the HCUP-NIS severity data file comorbidity index. Costs for obese patients were
      compared with those for nonobese patients. To control for medical complexity,
      each obese patient was matched one-to-one with a nonobese patient using age, sex,
      race, and 28 comorbid defined elements. RESULTS: Of 2,309,699 procedures,
      439,8129 (19%) were successfully matched into 2 medically equal groups (obese vs
      nonobese). Adjusted total hospital costs incurred by obese patients were 3.7%
      higher with a significantly (P < 0.0001) higher per capita cost of $648 (95%
      confidence interval [CI]: $556-$736) compared with nonobese patients. Of the 2
      major components of hospital costs, length of stay was significantly increased in
      obese patients (mean difference = 0.0253 days, 95% CI: 0.0225-0.0282) and
      resource utilization determined by costs per day were greater in obese patients
      due to an increased number of diagnostic and therapeutic procedures needed
      postoperatively (odds ratio [OR] = 0.94, 95% CI: 0.93-0.96). Postoperative
      complications were equivalent in both groups (OR = 0.97, 95% CI: 0.93-1.02).
      CONCLUSIONS: Annual national hospital expenditures for the largest volume
      surgical procedures is an estimated $160 million higher in obese than in a
      comparative group of nonobese patients.

PMID- 23979270
TI  - Survival outcome of local excision versus radical resection of colon or rectal
      carcinoma: a Surveillance, Epidemiology, and End Results (SEER) population-based
      study.
AB  - OBJECTIVE: To compare cancer-specific results of local excision with major
      resection. BACKGROUND: Technological advances have enabled endoscopic and local
      excision techniques to be applied in the treatment of early colorectal cancer in
      preference to radical surgery. METHOD: Patients with stage 0 (carcinoma in situ)
      or stage I (T1/2N0M0) adenocarcinoma of the colon or rectum undergoing surgery
      between 1998 and 2009 were included from the SEER (Surveillance, Epidemiology,
      and End Results) database. Local excision (endoscopic or surgical) was compared
      with major surgical resection using adjusted hazard ratios (HRs) for 5-year
      cancer-specific survival (CSS). RESULTS: This study included 7378 local excisions
      and 36,116 major resections. There were 3553 patients with carcinoma in situ and
      39,941 with clinical stage I cancer. Local tumor excision for carcinoma in situ
      was associated with equivalent CSS compared to major resection (HRs = 1.06, P =
      0.814, for colon and 0.78, P = 0.494, for rectum). Local excision of T1 and T2
      colon cancer was associated with reduced CSS (HR = 1.31, P = 0.020, and 2.89, P <
      0.001, respectively). Local excision of T1 rectal cancer did not affect CSS (HR =
      1.16, P = 0.236), but it significantly reduced CSS for T2 cancer (HR = 1.71, P <
      0.001). Subgroup analysis of T1 and T2 rectal cancer after neoadjuvant therapy
      and local excision showed oncological equivalence to major resection (HR = 1.12,
      P = 0.802, and 1.23, P = 0.802). CONCLUSIONS: Local excision for early colorectal
      cancer was oncologically equivalent to major surgery for carcinoma in situ and T1
      rectal cancer, but inferior for T1-2 colon and T2 rectal cancer. Exploratory data
      suggest local excision of T1-2 rectal cancer after neoadjuvant therapy may be
      safe.

PMID- 23979271
TI  - Minority trauma patients tend to cluster at trauma centers with worse-than
      expected mortality: can this phenomenon help explain racial disparities in trauma
      outcomes?
AB  - OBJECTIVES: To determine whether minority trauma patients are more commonly
      treated at trauma centers (TCs) with worse observed-to-expected (O/E) survival.
      BACKGROUND: Racial disparities in survival after traumatic injury have been
      described. However, the mechanisms that lead to these inequities are not well
      understood. METHODS: Analysis of level I/II TCs included in the National Trauma
      Data Bank 2007-2010. White, Black, and Hispanic patients 16 years or older
      sustaining blunt/penetrating injuries with an Injury Severity Score of 9 or more
      were included. TCs with 50% or more Hispanic or Black patients were classified as
      predominantly minority TCs. Multivariate logistic regression adjusting for
      several patient/injury characteristics was used to predict the expected number of
      deaths for each TC. O/E mortality ratios were then generated and used to rank
      individual TCs as low (O/E <1), intermediate, or high mortality (O/E >1).
      RESULTS: A total of 556,720 patients from 181 TCs were analyzed; 86 TCs (48%)
      were classified as low mortality, 6 (3%) intermediate, and 89 (49%) as high
      mortality. More of the predominantly minority TCs [(82% (22/27) vs 44% (67/154)]
      were classified as high mortality (P < 0.001). Approximately 64% of Black
      patients (55,673/87,575) were treated at high-mortality TCs compared with 54%
      Hispanics (32,677/60,761) and 41% Whites (165,494/408,384) (P < 0.001).
      CONCLUSIONS: Minority trauma patients are clustered at hospitals with
      significantly higher-than-expected mortality. Black and Hispanic patients treated
      at low-mortality hospitals have a significantly lower odds of death than similar
      patients treated at high-mortality hospitals. Differences in TC outcomes and
      quality of care may partially explain trauma outcomes disparities.

PMID- 23979272
TI  - Slower walking speed forecasts increased postoperative morbidity and 1-year
      mortality across surgical specialties.
AB  - OBJECTIVE: The purpose of this study was to determine the relationship between
      the Timed Up and Go test and postoperative morbidity and 1-year mortality, and to
      compare the Timed Up and Go to the standard-of-care surgical risk calculators for
      prediction of postoperative complications. METHODS: In this prospective cohort
      study, patients 65 years and older undergoing elective colorectal and cardiac
      operations with a minimum of 1-year follow-up were included. The Timed Up and Go
      test was performed preoperatively. This timed test starts with the subject
      standing from a chair, walking 10 feet, returning to the chair, and ends after
      the subject sits. Timed Up and Go results were grouped as fast <= 10 seconds,
      intermediate = 11-14 seconds, and slow >= 15 seconds. Receiver operating
      characteristic curves were used to compare the 3 Timed Up and Go groups to
      current standard-of-care surgical risk calculators at forecasting postoperative
      complications. RESULTS: This study included 272 subjects (mean age of 74 +/- 6
      years). Slower Timed Up and Go was associated with increased postoperative
      complications after colorectal (fast 13%, intermediate 29%, and slow 77%; P <
      0.001) and cardiac (fast 11%, intermediate 26%, and slow 52%; P < 0.001)
      operations. Slower Timed Up and Go was associated with increased 1-year mortality
      following both colorectal (fast 3%, intermediate 10%, and slow 31%; P = 0.006)
      and cardiac (fast 2%, intermediate 3%, and slow 12%; P = 0.039) operations.
      Receiver operating characteristic area under curve of the Timed Up and Go and the
      risk calculators for the colorectal group was 0.775 (95% CI: 0.670-0.880) and
      0.554 (95% CI: 0.499-0.609), and for the cardiac group was 0.684 (95% CI: 0.603
      0.766) and 0.552 (95% CI: 0.477-0.626). CONCLUSIONS: Slower Timed Up and Go
      forecasted increased postoperative complications and 1-year mortality across
      surgical specialties. Regardless of operation performed, the Timed Up and Go
      compared favorably to the more complex risk calculators at forecasting
      postoperative complications.

PMID- 23979273
TI  - Elevated levels of plasma mitochondrial DNA DAMPs are linked to clinical outcome
      in severely injured human subjects.
AB  - OBJECTIVE: Our objective was to execute a prospective cohort study to determine
      relationships between plasma mtDNA DAMP levels and the occurrence of systemic
      inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome
      (MODS), and mortality. BACKGROUND: Mitochondrial DNA damage-associated molecular
      patterns (DAMPs) accumulate in the circulation after severe injury. Observations
      in animal models demonstrate that mtDNA DAMPs contribute to organ dysfunction;
      however, the link between plasma mtDNA DAMPs and outcome in severely injured
      human subjects has not been established. METHODS: DNA was isolated from plasma
      samples taken from severely injured patients at hospital days 0, 1, and 2. Real
      time PCR was used to quantify selected ~200 base pair sequences of mtDNA within
      the COX1, ND1, and ND6 genes, as well as from the D-Loop transcriptional
      regulatory region. MODS was defined as a Denver Multiple Organ Failure score of 4
      or greater. RESULTS: MtDNA DAMPs were quantified as PCR threshold cycle number.
      Lower threshold cycles indicate increased mtDNA DAMP content. Patients with SIRS
      had significantly increased mtDNA DAMP levels in all 4 sequences examined (32.14
      +/- 0.90 vs 29.00 +/- 1.15 for COX1, 31.90 +/- 0.47 vs 30.16 +/- 1.42 for ND1,
      32.40 +/- 0.61 vs 28.94 +/- 1.13 for ND6, and 33.12 +/- 0.83 vs 28.30 +/- 1.14
      for D-Loop). Patients who developed MODS also had elevated mtDNA DAMP levels
      compared with those who did not (32.57 +/- 0.74 vs 27.12 +/- 0.66 for COX1, 32.45
      +/- 0.65 vs 28.20 +/- 0.73 for ND1, 32.52 +/- 0.56 vs 27.60 +/- 0.79 for ND6, and
      32.85 +/- 0.75 vs 27.86 +/- 1.27 for D-Loop). Patients with above-median mtDNA
      DAMP levels had a significantly elevated relative risk for mortality. Four
      patients died secondary to severe MODS. CONCLUSIONS: These findings comprise the
      first observational evidence that plasma mtDNA DAMPs is associated with the
      evolution of SIRS, MODS, and mortality in severely injured human subjects.

PMID- 23979274
TI  - The clinical significance of an elevated postoperative glucose value in
      nondiabetic patients after colorectal surgery: evidence for the need for tight
      glucose control?
AB  - OBJECTIVES: To evaluate the significance of hyperglycemia in patients without a
      preoperative diagnosis of diabetes undergoing elective colorectal surgery.
      METHODS: Preoperative and all postoperative blood glucose measurements were
      retrieved for 2628 consecutive patients undergoing elective colorectal resection
      within 2 years at 1 center. Nondiabetic patients were identified as those without
      a preoperative diagnosis of diabetes and/or based on HbA1C levels. The
      association between any elevated postoperative random glucose value
      (hyperglycemia: >125 mg/dL) and level of elevation (>125 mg/dL or >200 mg/dL)
      within 72 hours of surgery in nondiabetic patients with 30-day mortality and
      infectious and noninfectious complications was assessed. RESULTS: Evaluation of
      16,404 postoperative glucose measurements for all 2447 nondiabetic patients who
      underwent surgery in 2010 and 2011 revealed that 66.7% patients experienced
      hyperglycemia. Degree of hyperglycemia correlated with increasing American
      Society of Anesthesiologists class and surgical severity (blood loss).
      Hyperglycemia was associated with infectious and noninfectious complications and
      mortality, the rates of these complications increasing parallel to the degree of
      hyperglycemia. Hyperglycemia was independently associated with septic
      complications (P = 0.024). CONCLUSIONS: Postoperative hyperglycemia is frequent
      after elective colorectal surgery in nondiabetic patients. Even a single
      postoperative elevated glucose value is adversely associated with morbidity and
      mortality; this risk is related to the degree of glucose elevation. These
      findings strongly support monitoring of glucose values and early consideration of
      management strategies for glycemic control after surgery even in nondiabetic
      patients.

PMID- 23979275
TI  - Improving mortality following emergent surgery in older patients requires focus
      on complication rescue.
AB  - OBJECTIVE: To determine whether a hospital's ability to rescue patients from
      major complications underlies variation in outcomes for elderly patients
      undergoing emergent surgery. BACKGROUND: Perioperative mortality rates in elderly
      patients undergoing emergent general/vascular operations are high and vary widely
      across Michigan hospitals. METHODS: We identified 23,224 patients undergoing
      emergent general/vascular surgical procedures at 41 hospitals within the Michigan
      Surgical Quality Collaborative between 2006 and 2011. Hospitals were ranked by
      risk- and reliability-adjusted 30-day mortality rates and grouped into tertiles.
      We stratified patients by age (<75 and >=75 years). Risk-adjusted major
      complication and failure-to-rescue (ie, mortality after major complication) rates
      were determined for each tertile of hospital mortality. RESULTS: Risk-adjusted
      mortality rates in elderly patients varied 2-fold across all hospitals.
      Complication rates correlated poorly with mortality. Failure-to-rescue rates,
      however, were markedly higher in high-mortality hospitals (29% lowest tertile vs
      41% highest tertile; P < 0.01). When compared with younger patients, overall
      failure-to-rescue rates were almost 2-fold greater in the elderly (36.1% >=75 vs
      18.7% <75; P < 0.01). CONCLUSIONS: A hospital's failure to rescue patients from
      major complications seems to underlie the variation in mortality rates across
      Michigan hospitals after emergent surgery. Although higher failure-to-rescue
      rates in the elderly may signify their diminished physiological reserve for
      surviving critical illness, the wide variation across hospitals also highlights
      the importance of systems aimed at the early recognition and effective management
      of major complications in this vulnerable population.

PMID- 23979276
TI  - Mobilization of the obese patient and prevention of injury.
AB  - OBJECTIVES AND BACKGROUND: Obese patients are difficult to transport between
      emergency departments, imaging facilities, operating rooms, intensive care units,
      acute care units, and rehabilitation facilities. Each move, along with turning,
      bathing, and access to bathrooms, poses risks of injury to patients and
      personnel. Similarly, inadequate mobilization raises the risk of pressure ulcers.
      The costs can be prohibitive. METHODS: On 6 pilot units, mobilization of patients
      was delegated to trained lift team technicians who covered the units in pairs, 24
      hours per day, 7 days per week, to assist with moving and lifting of patients
      weighing 200 pounds or more, with a Braden Scale score of 18 or less and/or the
      presence of pressure ulcers. RESULTS: In fiscal year 2012, hospital-acquired
      pressure ulcers on pilot units decreased by 43% (from 61 to 35). Patient handling
      related employee injuries on pilot units decreased by 38.5% (from 13 to 8).
      Employee satisfaction related to organizational commitment to employee safety and
      impact on job satisfaction was positively impacted by implementation of the lift
      team. With the reduction in employee injuries and the fall in the prevalence of
      pressure ulcers, the adoption of the lift team program decreased costs by
      $493,293.00. CONCLUSIONS: Implementation of lift teams on pilot nursing units
      decreased patient handling-related employee injuries, resulting in sharp
      improvements in quality patient care and reduced costs.

PMID- 23979277
TI  - Volumetric gain of the liver after major hepatectomy in obese patients: a case
      matched study in 84 patients.
AB  - OBJECTIVE: The objective was to determine the liver volumetric recovering
      capacity and postoperative course after major hepatectomy in obese patients
      through a case-matched study. BACKGROUND: In literature, the impact of obesity on
      liver recovering has been analyzed only indirectly in terms of morbimortality but
      never through volumetric assessment. PATIENTS AND METHOD: Between 2005 and 2011,
      42 patients with body mass index (BMI) 30 or higher (Ob group) underwent major
      hepatectomy and were matched with 42 patients with BMI 25 or lower (NonOb group)
      on the magnitude of resection (number of resected segments +/-1, remnant liver
      volume to total liver volume, RLV/TLV, +/-5%). The RLV was measured on computed
      tomographic slices preoperatively and postoperatively at 1 month (RLV-1M) for all
      patients and within 3 to 12 months in 42 paired patients (median = 6 months, RLV
      6M). Considering hepatomegaly in Ob group, RLV was also normalized to body weight
      (RLVBWR). The liver volumetric gain was expressed as a relative increase [(RLV-1M
      - RLV)/RLV] or increase in RLVBWR. RESULTS: The Ob and NonOb groups were
      comparable regarding clinicopathological data, except for arterial hypertension
      (48% vs 19%; P = 0.005), mean steatosis (24% vs 10%; P = 0.03), and fibrosis
      incidence (33% vs 10%; P = 0.008). Ob group showed longer operative time and
      higher blood losses. There were no intergroup differences in liver failure (both
      7.1%) and 90-day morbimortality. Despite comparable RLV/TLV (38.1% vs 37.7%; P =
      0.13), the relative liver volumetric gain at 1 month was significantly lower in
      Ob group (+93% vs +115%; P = 0.002), as well as RLVBWR increase (+0.59% vs
      +0.79%; P < 0.001). The RLV-1M represented 66.2% of initial TLV in Ob group
      compared with 73.8% (P = 0.005) in NonOb group. This delay in relative volumetric
      gain persisted at 6 months (+105.4% vs +137.6%; P = 0.009), the RLV-6M
      representing 71.2% vs 82.4% of initial TLV (P = 0.014). CONCLUSIONS: In a
      methodologically robust trial in the first cohort reported up to date, the
      regenerative response in obese patients was comparatively slower based on their
      initial TLV or body weight.

PMID- 23979278
TI  - Gastric bypass leads to improvement of diabetic neuropathy independent of glucose
      normalization--results of a prospective cohort study (DiaSurg 1 study).
AB  - OBJECTIVE: Surprisingly, 40% to 95% of patients with type 2 diabetes mellitus
      (T2DM) show early remission of hyperglycemia after obesity surgery. It is unknown
      to what extent other diabetes-associated comorbidities such as distal peripheral
      neuropathy (DPN) might be influenced by obesity surgery. This pilot study aimed
      at providing further evidence for the impact of Roux-en-Y gastric bypass (RYGB)
      on both glycemic control and DPN in non-severely obese patients with insulin
      dependent T2DM. METHODS: In the present prospective cohort study, 20 patients
      with long-standing, insulin-dependent T2DM and a body mass index (BMI) between 25
      and 35 kg/m underwent laparoscopic RYGB. Body mass index, glycosylated hemoglobin
      (HbA1c), and DPN [quantified by the Neuropathy Symptom Score (NSS) and the
      Neuropathy Deficit Score (NDS)] were investigated. RESULTS: Six months after
      surgery, the preoperative BMI of 32.8 +/- 2.1 kg/m (mean +/- standard deviation)
      dropped to 25.6 +/- 2.5 kg/m (P < 0.001). Preoperative HbA1c levels decreased
      from 8.5 +/- 1.2% to 7.1 +/- 1.2% (P < 0.001), with 15% of patients having a
      normalized HbA1c level lower than 6.2%. Of 12 patients with documented DPN, the
      median NSS was 8 (range, 0-10) preoperatively and 0 (range, 0-9) postoperatively
      (P = 0.004), with 8 patients scoring an NSS of 0. The median NDS was 6 (range, 2
      8) preoperatively and 4 (range, 0-8) postoperatively (P = 0.027), with 1 patient
      scoring an NDS of 0. All patients had an improvement or normalization in either 1
      or both scores. CONCLUSIONS: As expected, BMI and HbA1c levels improved
      significantly after RYGB. More interestingly, neuropathy scores, such as NSS and
      NDS, improved significantly early after surgery. Symptomatic neuropathy was
      completely reversible in 67% of the patients. These findings add further evidence
      to the fact that RYGB might be a valuable treatment option not only for improving
      glycemic control but also for reducing diabetes-associated comorbidities, such as
      DPN. This points to a complex metabolic effect of RYGB that exceeds glucose
      normalization. However, the results still need to be confirmed in controlled
      trials.

PMID- 23979279
TI  - Comment on the article about comparison of outcomes of laparoscopic and open
      appendectomy in management of uncomplicated and complicated appendicitis.

PMID- 23979280
TI  - Breast lymphomas around breast implants.

PMID- 23979281
TI  - Liberal resection for (presumed) Sendai negative branch-duct intraductal
      papillary mucinous neoplasms--also not harmless.

PMID- 23979282
TI  - Reply to letter: "Anaplastic large cell lymphomas and breast implants".

PMID- 23979283
TI  - Reply to letter: "Author response to the comment on the article about comparison
      of outcomes of laparoscopic and open appendectomy in management of uncomplicated
      and complicated appendicitis".

PMID- 23979284
TI  - Reply to letter: "Influence of surgical margins on outcome in patients with
      intrahepatic cholangiocarcinoma: the pitfalls of the study".

PMID- 23979285
TI  - Reply to letter: "Liberal resection for (presumed) Sendai negative branch-duct
      IPMN--also not harmless".

PMID- 23979286
TI  - Comparative operative outcomes of early and delayed cholecystectomy for acute
      cholecystitis: a population-based propensity score analysis.
AB  - OBJECTIVE: To compare the operative outcomes of early and delayed cholecystectomy
      for acute cholecystitis. BACKGROUND: Randomized trials comparing early to delayed
      cholecystectomy for acute cholecystitis have limited contemporary external
      validity. Furthermore, no study to date has been large enough to assess the
      impact of timing of cholecystectomy on the frequency of serious rare
      complications including bile duct injury and death. METHODS: This is a population
      based retrospective cohort study of patients emergently admitted to hospital with
      acute cholecystitis and managed with cholecystectomy over the period of April 1,
      2004, to March 31, 2011. We used administrative records for the province of
      Ontario, Canada. Patients were divided into 2 exposure groups: those who
      underwent cholecystectomy within 7 days of emergency department presentation on
      index admission (early cholecystectomy) and those whose cholecystectomy was
      delayed. The primary outcome was major bile duct injury requiring operative
      repair within 6 months of cholecystectomy. Secondary outcomes included major bile
      duct injury or death, 30-day postcholecystectomy mortality, completion of
      cholecystectomy with an open approach, conversion among laparoscopic cases, and
      total hospital length of stay. Propensity score methods were used to address
      confounding by indication. RESULTS: From 22,202 patients, a well-balanced matched
      cohort of 14,220 patients was defined. Early cholecystectomy was associated with
      a lower risk of major bile duct injury [0.28% vs 0.53%, relative risk (RR)=0.53,
      95% confidence interval [CI]: 0.31-0.90], of major bile duct injury or death
      (1.36% vs 1.88%, RR=0.72, 95% CI: 0.56-0.94), and, albeit non-significant, of 30
      day mortality (0.46% vs 0.64%, RR=0.73, 95% CI: 0.47-1.15). Total hospital length
      of stay was shorter with early cholecystectomy (mean difference 1.9 days, 95% CI:
      1.7-2.1). No significant differences were observed in terms, open cholecystectomy
      (15% vs 14%, RR=1.07, 95% CI: 0.99-1.16) or in conversion among laparoscopic
      cases (11% vs 10%, RR=1.02, 95% CI: 0.93-1.13). CONCLUSIONS: These results
      support the benefit of early overdelayed cholecystectomy for patients with acute
      cholecystitis.

PMID- 23979287
TI  - An interactive individualized intervention to promote behavioral change to
      increase personal well-being in US surgeons.
AB  - OBJECTIVE: Evaluate the utility of a computer-based, interactive, and
      individualized intervention for promoting well-being in US surgeons. BACKGROUND:
      Distress and burnout are common among US surgeons. Surgeons experiencing distress
      are unlikely to seek help on their own initiative. A belief that distress and
      burnout are a normal part of being a physician and lack of awareness of distress
      level relative to colleagues may contribute to this problem. METHODS: Surgeons
      who were members of the American College of Surgeons were invited to participate
      in an intervention study. Participating surgeons completed a 3-step, interactive,
      electronic intervention. First, surgeons subjectively assessed their well-being
      relative to colleagues. Second, surgeons completed the 7-item Mayo Clinic
      Physician Well-Being Index and received objective, individualized feedback about
      their well-being relative to national physician norms. Third, surgeons evaluated
      the usefulness of the feedback and whether they intended to make specific changes
      as a result. RESULTS: A total of 1150 US surgeons volunteered to participate in
      the study. Surgeons' subjective assessment of their well-being relative to
      colleagues was poor. A majority of surgeons (89.2%) believed that their well
      being was at or above average, including 70.5% with scores in the bottom 30%
      relative to national norms. After receiving objective, individualized feedback
      based on the Mayo Clinic Physician Well-Being Index score, 46.6% of surgeons
      indicated that they intended to make specific changes as a result. Surgeons with
      lower well-being scores were more likely to make changes in each dimension
      assessed (all Ps<0.001). CONCLUSIONS: US surgeons do not reliably calibrate their
      level of distress. After self-assessment and individualized feedback using the
      Mayo Clinic Physician Well-Being Index, half of participating surgeons reported
      that they were contemplating behavioral changes to improve personal well-being.

PMID- 23979288
TI  - Effect of gastric bypass versus diet on cardiovascular risk factors.
AB  - OBJECTIVE: To assess the effect of Roux-en-Y gastric bypass (RYGB) on high
      density lipoprotein cholesterol (HDL-C) concentration and its apolipoprotein A4
      (ApoA4) content at 1 year after bariatric surgery in comparison with a
      hypocaloric diet. Secondary aim was to measure total cholesterol and
      triglycerides levels and insulin sensitivity after interventions. BACKGROUND:
      Very few prospective uncontrolled studies have investigated the effects of RYGB
      on cardiovascular risk factors. No controlled studies had as primary goal the
      changes in HDL-C after gastric bypass. METHODS: Forty subjects with a body mass
      index more than 40 or 35 kg/m or more in the presence of diabetes were enrolled.
      Twenty of them underwent RYGB, whereas 20 received lifestyle modification
      suggestions and medical therapy for obesity complications (diabetes,
      hypertension, and hyperlipidemia). RESULTS: A significant (P < 0.0001) increase
      in HDL-C concentrations was observed only in the surgical arm (from 41.95 +/-
      7.24 to 56.55 +/- 9.01 mg/dL). Mean systolic and diastolic blood pressures were
      significantly reduced (P < 0.0001) in both groups with no between-group
      differences, probably in relation to the optimization of the antihypertensive
      treatment. Plasma concentration of ApoA4, a major HDL-C protein fraction,
      significantly increased 1 year after RYGB (from 496.61 +/- 400.41 to 987.88 +/-
      637.41MUg/L, P < 0.01). Circulating triglycerides concentration significantly
      decreased after surgery, whereas both peripheral and hepatic insulin resistance
      increased significantly. CONCLUSIONS: Our study shows that HDL-C and ApoA4
      significantly increase after gastric bypass and that this increase is associated
      with a net improvement in hepatic insulin sensitivity. Furthermore, we speculate
      that ApoA4, which induces satiety in animals, can eventually play a role on the
      appetite reduction after RYGB because there is a strict and inverse relationship
      between weight and ApoA4 changes. (NCT01707771).

PMID- 23979290
TI  - Influence of surgical margins on outcome in patients with intrahepatic
      cholangiocarcinoma: a multicenter study by the AFC-IHCC-2009 Study Group.

PMID- 23979289
TI  - A statewide colectomy experience: the role of full bowel preparation in
      preventing surgical site infection.
AB  - OBJECTIVE: To assess the utility of full bowel preparation with oral
      nonabsorbable antibiotics in preventing infectious complications after elective
      colectomy. BACKGROUND: Bowel preparation before elective colectomy remains
      controversial. We hypothesize that mechanical bowel preparation with
      nonabsorbable oral antibiotics is associated with a decreased rate of
      postoperative infectious complications when compared with no bowel preparation.
      METHODS: Patient and clinical data were obtained from the Michigan Surgical
      Quality Collaborative-Colectomy Best Practices Project. Propensity score analysis
      was used to match elective colectomy cases based on primary exposure variable
      full bowel preparation (mechanical bowel preparation with nonabsorbable oral
      antibiotics) or no bowel preparation (neither mechanical bowel preparation given
      nor nonabsorbable oral antibiotic given). The primary outcomes for this study
      were occurrence of surgical site infection and Clostridium difficile colitis.
      RESULTS: In total, 2475 cases met the study criteria. Propensity analysis created
      957 paired cases (n = 1914) differing only by the type of bowel preparation.
      Patients receiving full preparation were less likely to have any surgical site
      infection (5.0% vs 9.7%; P = 0.0001), organ space infection (1.6% vs 3.1%; P =
      0.024), and superficial surgical site infection (3.0% vs 6.0%; P = 0.001).
      Patients receiving full preparation were also less likely to develop
      postoperative C difficile colitis (0.5% vs 1.8%, P = 0.01). CONCLUSIONS: In the
      state of Michigan, full bowel preparation is associated with decreased infectious
      complications after elective colectomy. Within this context, the Michigan
      Surgical Quality Collaborative recommends full bowel preparation before elective
      colectomy.

PMID- 23979291
TI  - Outcome of percutaneous tibial nerve stimulation (PTNS) for fecal incontinence: a
      prospective cohort study.
AB  - OBJECTIVES: The aim of this study was to assess the long-term efficacy of
      percutaneous tibial nerve stimulation (PTNS) in fecal incontinence (FI).
      BACKGROUND: There is extensive evidence regarding the efficacy of PTNS in urinary
      incontinence. Data on the efficacy of PTNS for FI are limited to a few small case
      series with relatively short-follow up. METHODS: A prospective cohort of patients
      with FI was studied. Incontinence scores were measured using a validated
      questionnaire (Cleveland Clinic Florida-FI score) at specific time points: before
      treatment, after completion of a treatment course (12 PTNS sessions), and before
      the last maintenance ("top-up") therapy. Deferment time and average number of
      weekly incontinence episodes were also estimated from a prospective bowel dairy
      kept by the patient at these time points. Quality of life was assessed with the
      Rockwood Fecal Incontinence Quality of Life questionnaire. RESULTS: A total of
      150 patients were recruited to the study between January 2008 and June 2012.
      Analysis was performed on 115 patients who continued to receive PTNS after a
      median follow-up of 26 (range, 12-42) months. The baseline Cleveland Clinic
      Florida-FI score +/-SD (12.0 +/- 3.9) improved after 12 PTNS sessions (9.4 +/-
      4.6, P < 0.0001) and after "top-up" treatments (10.0 +/- 4.3, P < 0.0001). The
      increase in the Cleveland Clinic Florida-FI score between the end of the 12th
      session and the last "top-up" therapy was also significant (P = 0.04). A similar
      pattern was seen for the deferment time and the quality of life scores. The
      median time between "top-up" sessions was 12 months (range, 1-40 months),
      significantly longer than the recommended interval of 6 months. CONCLUSIONS: PTNS
      is a well-tolerated treatment with high acceptability in the majority of
      patients. It provides a sustained improvement in FI up to 42 months in a
      relatively noninvasive manner. The effect of PTNS diminishes with time and
      additional therapy sessions at 6 monthly intervals may result in greater
      improvements. PTNS ought to be considered as the first step in all patients with
      FI refractory to maximum conservative therapies.

PMID- 23979292
TI  - Surgical curability of medullary thyroid cancer in multiple endocrine neoplasia
      2B: a changing perspective.
AB  - OBJECTIVE: This investigation aimed at exploring the suitability of nonendocrine
      manifestations preceding medullary thyroid cancer (MTC) for early diagnosis of
      multiple endocrine neoplasia type 2B (MEN 2B). BACKGROUND: MEN 2B patients,
      running a high risk of metastatic MTC, must be diagnosed early for biochemical
      cure. METHODS: Forty-four MEN 2B patients carrying inherited (3 patients) and de
      novo (41 patients) M918T RET mutations were examined for signs and symptoms
      prompting MEN 2B. RESULTS: All 3 patients with inherited mutations were diagnosed
      before the age of 1 year and cured of their C-cell disease. Among 41 patients
      with de novo mutations, MEN 2B was diagnosed in 12 patients after recognition of
      nonendocrine manifestations [intestinal ganglioneuromatosis (6 patients), oral
      symptoms (5 patients), ocular ("tearless crying") (4 patients), and skeletal
      stigmata (1 patient) alone or concomitantly]. In the remaining 29 patients with
      de novo mutations, the diagnosis of MEN 2B was triggered by symptomatic MTC (28
      patients) or pheochromocytoma (1 patient). The former patients, being
      significantly (P < 0.001) younger (means of 5.3 vs 17.6 years) and having lower
      calcitonin levels (means of 115 vs 25,519 pg/mL), smaller tumors (67% vs 0% were
      <=10 mm) and less often extrathyroidal extension (0% vs 81%), lymph node (42% vs
      100%), and distant metastases (8% vs 79%), were biochemically cured more often
      (58% vs 0%). CONCLUSIONS: MTC is curable in patients with de novo mutations when
      nonendocrine MEN 2B components are quickly appreciated and surgical intervention
      is performed before patients turn 4 years old.

PMID- 23979294
TI  - Policing online professionalism: are we too alarmist?

PMID- 23979293
TI  - Synthesis of VIP-lipopeptide using a new linker to modify liposomes: towards the
      development of a drug delivery system for active targeting.
AB  - A new component for the solid phase peptide synthesis of lipopeptide, 2-[(4R,5R)
      5-({[(9H-fluoren-9-yl)methoxy]carbonylaminomethyl}-2,2-dimethyl-1,3-dioxolan-4
      yl)methoxy]acetic acid (2), was designed and synthesized from (-)-2,3-O
      isopropylidene-D-threitol (3) in 4 steps. The key step was the selective
      alkylation of 3 with benzyl bromoacetate in the presence of Cs2CO3. Vasoactive
      intestinal peptide (VIP)-lipopeptide (1) incorporating this linker was
      synthesized by solid phase peptide synthesis. 

PMID- 23979295
TI  - Unraveling heterogeneous microviscosities of the 1-alkyl-3-methylimidazolium
      hexafluorophosphate ionic liquids with different chain lengths.
AB  - The rotational dynamics of coumarin 153 (C153) have been investigated in a series
      of 1-alkyl-3-methylimidazolium hexafluorophosphate ionic liquids with different
      alkyl chain lengths (alkyl = butyl, pentyl, hexyl, heptyl, octyl) ([Cnmim][PF6],
      n = 4-8) to examine the alkyl chain length dependent local viscosity of the
      microenvironment surrounding the probe molecules. The excimer-to-monomer
      fluorescence emission intensity ratio (IE/IM) of a well-known microviscosity
      probe, 1,3-bis(1-pyrenyl)propane (BPP), is also employed to study the
      microviscosity of [Cnmim][PF6] as a complementary measurement. The rotational
      dynamics of C153 show that at a certain length of the alkyl chain there are
      incompact and compact domains within [Cnmim][PF6], resulting in fast and slow
      components of C153 rotational dynamics. The microviscosities in different
      structural domains of [Cnmim][PF6] with different alkyl chain lengths are
      investigated by studying the fluorescence anisotropy decay of probe molecules.
      The obtained average rotation time constants show that with an increase in the
      length of the alkyl chain, the microviscosity of [Cnmim][PF6] is obviously
      increased first and then slightly decreased. The steady state fluorescence
      measurements with the microviscosity probe of BPP further prove that the
      microviscosity is not increased as much as expected when ionic liquids
      [Cnmim][PF6] have a relatively long alkyl chain. The different heterogeneous
      structures of [Cnmim][PF6] with different lengths of the alkyl chain are proposed
      to interpret the unusual microviscosity behaviors.

PMID- 23979296
TI  - The bidirectional relationships between online victimization and psychosocial
      problems in adolescents: a comparison with real-life victimization.
AB  - Although peer victimization is of major concern and adolescents spend increasing
      amounts of time on the Internet, relatively little is known about the
      psychosocial antecedents and consequences of online victimization. The main aim
      of this study was to compare the psychosocial antecedents and consequences of
      online versus real-life victimization. More specifically, the bidirectional
      relationship between online and real-life victimization on the one hand and
      psychosocial problems (i.e., loneliness and social anxiety) on the other was
      examined. In addition, the moderating role of online aggression in the
      relationship between online victimization and subsequent psychosocial problems
      was studied. This prospective study, consisting of three annual measurements, was
      conducted among a sample of 831 adolescents (50.3 % girls) aged 11-15, of which
      most (80.2 %) had a Dutch ethnic background. The results indicate a
      unidirectional relationship whereby loneliness and social anxiety predict an
      increase in latter online victimization rather than the reverse. A bidirectional
      relationship was found for real-life victimization: loneliness (but not social
      anxiety) predicted an increase in latter real-life victimization, which in turn
      predicted an increase in subsequent social anxiety (but not loneliness). No
      moderating effects of online aggression were found. The findings of the present
      study suggest that negative online and in real life peer interactions have a
      differential meaning for, and impact on adolescents' well-being.

PMID- 23979297
TI  - Testing new identity models and processes in French-speaking adolescents and
      emerging adults students.
AB  - Developing a sense of identity is a crucial psychosocial task for young people.
      The purpose of this study was to evaluate identity development in French-speaking
      adolescents and emerging adults (in France and Switzerland) using a process
      oriented model of identity formation including five dimensions (i.e., exploration
      in breadth, commitment making, exploration in depth, identification with
      commitment, and ruminative exploration). The study included participants from
      three different samples (total N = 2,239, 66.7 % women): two samples of emerging
      adult student and one sample of adolescents. Results confirmed the hypothesized
      five-factor dimensional model of identity in our three samples and provided
      evidence for convergent validity of the model. The results also indicated that
      exploration in depth might be subdivided in two aspects: a first form of
      exploration in depth leading to a better understanding and to an increase of the
      strength of current commitments and a second form of exploration in depth leading
      to a re-evaluation and a reconsideration of current commitments. Further, the
      identity status cluster solution that emerged is globally in line with previous
      literature (i.e., achievement, foreclosure, moratorium, carefree diffusion,
      diffused diffusion, undifferentiated). However, despite a structural similarity,
      we found variations in identity profiles because identity development is shaped
      by cultural context. These specific variations are discussed in light of social,
      educational and economic differences between France and the French-speaking part
      of Switzerland. Implications and suggestions for future research are offered. 

PMID- 23979298
TI  - A review of current research on the effects of progesterone.

PMID- 23979299
TI  - The hormonal link to breast cancer: the estrogen matrix.

PMID- 23979300
TI  - Aminophylline 3%, Co-dergocrine Mesylate 0.05%, and Isosorbide Dinitrate 0.25%
      Cream for the Treatment of Orgasmic Dysfunction in Women.

PMID- 23979301
TI  - Establishing an andropause practice.

PMID- 23979302
TI  - Compounding and the courts.

PMID- 23979303
TI  - Facilities and procedures for compounding hazardous drugs.

PMID- 23979304
TI  - Gaining access to investigational drugs for treatment: an investigational new
      drug application primer.

PMID- 23979305
TI  - Medications discontinued in the United States.

PMID- 23979306
TI  - Basics of compounding: iontophoresis, part 2.

PMID- 23979307
TI  - Stability of tubocurarine chloride injection at ambient temperature and 4 deg C
      in polypropylene syringes.
AB  - The stabililty of 3 mg/mL tubocurarine chloride injection in 3-mL polypropylene
      syringes stored at ambient temperature and at 4 deg C for up to 90 days was
      investigated. A high-performance liquid chromatographic stability-indicating
      assay was used to determine concentration levels of tubocurarine chloride
      injection 0, 1, 4, 7, 15, 30, 45, 60, and 90 days after preparation of the
      syringes. Benzyl alcohol, which was used as a preservative, did not interfere
      wiht the assay. At 25 deg C, the loss in potency was less than 10% after the
      syringes had been stored for 45 days; at 4 deg C, that loss was less than 1%
      after 90 days of storage. The pH of tubocurarine chloride injection did not
      change appreciably during the 90-day study period. 

PMID- 23979308
TI  - Compatibility screening of bivalirudin during simulated y-site administration
      with other drugs.
AB  - The physical compatibility of bivalirudin (Angiomax) with 96 selected other drugs
      during simulated Y-site injection was evaluated by visual observation, turbidity
      measurement, and electronic particle content assessment (when appropriate). Five
      milliliter samples of bivalirudin 5mg/mL in 5% dextrose injection were combined
      with 5mL of 96 other drugs (anti-infectives, analgesics, anihistamines,
      diuretics, steroids, or other supportive-care drugs that were either undiluted or
      diluted with either 5% dextrose injection or 0.9% sodium chloride injection [the
      diluent for drugs incompatible with 5% dextrose injection ]). Visual examinations
      were performed with the unaided eye in normal, diffuse fluorescent light with a
      Tydall beam (a high-intensity monodirectional light beam) to enhance the
      visualization of small particles and low-level turbidity. The turbidity of each
      sample was measured as well. The particle content of samples that did not exhibit
      a visible incompatibility was measured. Evaluation of the samples was performed
      initially and at 1 and 4 hours after preparation. Eighty-seven of the 96 test
      drugs were compatible with the bivalirudin dilution during the 4-hour observation
      period. However, the combination of bivalirudin solution with each of nine drugs
      resulted in haze formation, microparticulate formation, or gross preciptiation.
      Bivalirudin should not be administered simultaneously with those incompatible
      drugs. 

PMID- 23979309
TI  - Stability of Ketamine Hydrochloride Injection After Reconstitution in Water for
      Injection and Storagein 1-mL Tuberculin Polypropylene Syringes for Pediatric Use.
AB  - The stability of ketamine hydrochloride (10mg/mL) in water for injection stored
      in polypropylene syringes has been studied at 25 deg C by means of a stability
      indicating high-performance liquid chromatographic assay method. The
      concentrations of the drug were directly related to peak heights, and the percent
      relative standard deviation based on five injections was 1.9. The drug decomposed
      only when the solution was boiled after sodium hydroxide was added. It did not
      decompose in the presence of an acid or after 30 minutes of boiling. The
      injection did not lose potency after 30 days of storage at 25 deg C, and the pH
      value of 4.2 did not change. Ketamine hydrochloride appears to be a very stable
      drug. 

PMID- 23979310
TI  - 4D multimodality imaging of Citrobacter rodentium infections in mice.
AB  - This protocol outlines the steps required to longitudinally monitor a
      bioluminescent bacterial infection using composite 3D diffuse light imaging
      tomography with integrated MUCT (DLIT-MUCT) and the subsequent use of this data
      to generate a four dimensional (4D) movie of the infection cycle. To develop the
      4D infection movies and to validate the DLIT-MUCT imaging for bacterial infection
      studies using an IVIS Spectrum CT, we used infection with bioluminescent C.
      rodentium, which causes self-limiting colitis in mice. In this protocol, we
      outline the infection of mice with bioluminescent C. rodentium and non-invasive
      monitoring of colonization by daily DLIT-MUCT imaging and bacterial enumeration
      from feces for 8 days. The use of the IVIS Spectrum CT facilitates seamless co
      registration of optical and MUCT scans using a single imaging platform. The low
      dose MUCT modality enables the imaging of mice at multiple time points during
      infection, providing detailed anatomical localization of bioluminescent bacterial
      foci in 3D without causing artifacts from the cumulative radiation. Importantly,
      the 4D movies of infected mice provide a powerful analytical tool to monitor
      bacterial colonization dynamics in vivo.

PMID- 23979311
TI  - Choroidal thickness in convalescent vogt-koyanagi-harada disease.
AB  - PURPOSE: To evaluate the subfoveal choroidal thickness (SCT) at the convalescent
      stage of Vogt-Koyanagi-Harada disease and to investigate the correlations among
      SCT, the presence of the sunset glow fundus, and size of the peripapillary
      atrophy (PPA). METHODS: The medical records of consecutive patients with Vogt
      Koyanagi-Harada disease without active intraocular inflammation were reviewed,
      and one eye was randomly chosen for analyses. The disease duration was more than
      3 years. Enhanced depth imaging optical coherence tomography was performed to
      measure SCT. The area of PPA was measured using the PDT/MPS software. Sunset glow
      fundi were classified into two groups according to the degree of depigmentation.
      RESULTS: Nineteen eyes with Vogt-Koyanagi-Harada disease were studied. The mean
      SCT of 12 eyes with severe sunset glow fundus was 144 +/- 72 MUm which was
      thinner than that of the 7 eyes with no or mild depigmentation (P = 0.0057). The
      SCT was inversely correlated with the disease duration (P = 0.048) and the PPA
      area (P = 0.0002). The PPA area was positively correlated with the disease
      duration (P = 0.007). CONCLUSION: The thinner choroid and larger PPA areas were
      correlated with the degree of depigmentation or disease duration and might be
      caused by latent choroidal inflammation in the convalescent stage of Vogt
      Koyanagi-Harada disease.

PMID- 23979314
TI  - Lipids: Gut-derived lipid signal links dopamine deficiency and high-fat feeding.

PMID- 23979312
TI  - Promoter analysis reveals cis-regulatory motifs associated with the expression of
      the WRKY transcription factor CrWRKY1 in Catharanthus roseus.
AB  - WRKY transcription factors (TFs) are emerging as an important group of regulators
      of plant secondary metabolism. However, the cis-regulatory elements associated
      with their regulation have not been well characterized. We have previously
      demonstrated that CrWRKY1, a member of subgroup III of the WRKY TF family,
      regulates biosynthesis of terpenoid indole alkaloids in the ornamental and
      medicinal plant, Catharanthus roseus. Here, we report the isolation and
      functional characterization of the CrWRKY1 promoter. In silico analysis of the
      promoter sequence reveals the presence of several potential TF binding motifs,
      indicating the involvement of additional TFs in the regulation of the TIA
      pathway. The CrWRKY1 promoter can drive the expression of a beta-glucuronidase
      (GUS) reporter gene in native (C. roseus protoplasts and transgenic hairy roots)
      and heterologous (transgenic tobacco seedlings) systems. Analysis of 5'- or 3'
      end deletions indicates that the sequence located between positions -140 to -93
      bp and -3 to +113 bp, relative to the transcription start site, is critical for
      promoter activity. Mutation analysis shows that two overlapping as-1 elements and
      a CT-rich motif contribute significantly to promoter activity. The CrWRKY1
      promoter is induced in response to methyl jasmonate (MJ) treatment and the
      promoter region between -230 and -93 bp contains a putative MJ-responsive
      element. The CrWRKY1 promoter can potentially be used as a tool to isolate novel
      TFs involved in the regulation of the TIA pathway.

PMID- 23979317
TI  - Neuroendocrinology: FGF21-central pathways of action unravelled.

PMID- 23979319
TI  - Establishment of a pancreatic beta cell proliferation model in vitro and a
      platform for diabetes drug screening.
AB  - Diabetes, a disease resulting from loss of functional beta cells, is globally an
      increasingly important condition. Based on the islet-differentiation ability of
      ductal epithelial cells and stimulating beta cell proliferation ability of the
      Reg Ialpha gene, we aimed to establish an in vitro pancreatic beta cell
      proliferation model for screening therapeutic drugs of diabetes in the future.
      Pancreatic ductal epithelial cells were isolated from male Wistar rats, and
      induced to differentiate into pancreatic beta cells. Immunofluorescence staining
      assay, western blot, RT-PCR analysis, and dithizone staining were used to
      characterize the cells. Rat Reg Ialpha protein was transiently expressed in vitro
      by transfection of HEK 293 cells with the PCMV6-entry-REG Ia plasmid, and
      expression was verified by RT-PCR analysis, proliferation assay, and apoptosis
      assay. The pancreatic beta cell proliferation model was further validated by a
      proliferation assay using differentiated pancreatic beta cells treated with
      transfection supernatant. Finally, we have successfully established an in vitro
      pancreatic beta cells proliferation model using transiently expressed rat Reg
      Ialpha protein and differentiated pancreatic beta cells from pancreatic ductal
      epithelial cells. This model could be used as a platform to screen new drugs for
      islet neogenesis to cure diabetes, especially Chinese herbal drugs in the future.

PMID- 23979320
TI  - The influence of drinking-water pollution with heavy metal on the expression of
      IL-4 and IFN-gamma in mice by real-time polymerase chain reaction.
AB  - In recent years, water pollution has been converted to a challenging discussion
      in health area of human being. Heavy elements are one of the most important water
      pollutants and their negative adverse effects on body systems have been
      confirmed. In this study, investigation of effects of two heavy elements
      including lead (Pb) and copper (Cu) on expression of interlukin-4 (IL-4) and
      interferon-gamma (IFN-gamma) as humoral and cellular immunity biomarkers,
      respectively, was aimed and PCR, real-time PCR and electrophoresis techniques
      were used. In this study, BALB/c mice were studied that had free access to
      drinking water which contained Cu or Pb salts. After 2 weeks, spleens of mice
      were removed, RNA extracted, and cDNA was prepared for RT-PCR. Then the
      expression of IL-4 and IFN-gamma genes were assessed by real-time PCR. The
      expression of IFN-gamma was up-regulated in both treated groups and the
      expression of IL-4 was only up-regulated in the group treated with Cu and down
      regulated in the group treated with Pb. This study shows that the presence of
      heavy elements as drinking-water pollutants results in a disproportion of natural
      cytokines balances, and thus may result in a negative effect on immune system. 

PMID- 23979321
TI  - Characterization of growth and Oryctes rhinoceros nudivirus production in
      attached cultures of the DSIR-HA-1179 coleopteran insect cell line.
AB  - The DSIR-HA-1179 coleopteran cell line is a susceptible and permissive host to
      the Oryctes rhinoceros nudivirus (OrNV), which has been used as a biocontrol
      agent against the coconut rhinoceros beetle (Oryctes rhinoceros); a pest of palms
      in the Asia-Pacific region. However, little is known about growth and metabolism
      of this cell line, knowledge of which is necessary to develop an in vitro large
      scale OrNV production process. The strong anchorage-dependent characteristics of
      the cell line, its particular fragility and its tendency to form dense clumps
      when manipulated, are the most likely reasons that have precluded further
      development of the cell line. In order to characterize DSIR-HA-1179 cells, there
      was first a need for a reliable technique to count the cells. A homogenous cell
      suspension suitable for enumeration could be produced by treatment with TrypLE
      ExpressTM with optimum mean time for cell release calculated as 30 min. The cell
      line was adapted to grow in four serum-supplemented culture media namely TC-100,
      IPL-41, Sf-900 II and Sf-900 III and cell growth, glucose consumption, lactate
      and ammonia production were assessed from static-batch cultures. The maximum
      viable cell density was reached in Sf-900 II (17.9 * 10(5) cells/ml), with the
      maximum specific growth rate observed in this culture medium as well (0.0074 h(
      1)). Higher production of OrNV was observed in IPL-41 and TC-100 (4.1 * 10(7)
      TCID50/ml) than in cultures infected in Sf-900 III (2.0 * 10(7) TCID50/ml) and Sf
      900 II (1.4 * 10(7) TCID50/ml). At the end of the growth period, glucose was
      completely consumed in cultures grown in TC-100, while remained in excess in the
      other three culture media. The cell line produced lactate and ammonia to very low
      levels in the TC-100 culture medium which is a promising aspect for its
      cultivation at large-scale. 

PMID- 23979322
TI  - Neurodevelopmental outcomes at 4 to 8 years of children born at 22 to 25 weeks'
      gestational age: a meta-analysis.
AB  - IMPORTANCE: Many centers delivering infants at 22 to 25 weeks' gestation have
      limited data regarding their outcomes. A meta-analysis of the 4- to 8-year
      neurodevelopmental outcomes and exploration of the limitations of meta-analysis
      would aid physicians and parents to plan care for these infants. OBJECTIVES: To
      determine the rate of moderate to severe and severe neurodevelopmental impairment
      by gestational age in extremely preterm survivors followed up between ages 4 and
      8 years, as well as to determine whether there is a significant difference in
      impairment rates between the successive weeks of gestation of survivors. EVIDENCE
      REVIEW: A peer-reviewed search strategy obtained English-language publications
      from MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, and EMBASE.
      Personal files and reference lists from identified articles were searched.
      Contemporary cohorts were obtained by restriction to those published after 2004.
      Inclusion criteria were prospective cohort studies, follow-up rate of 65% or
      more, use of standardized testing or classification for impairment, reporting by
      gestation, and meeting prespecified definitions of impairment. We excluded
      randomized clinical trials, highly selective cohorts, consensus statements, and
      reviews. Of 1771 identified records, 89 full-text publications were assessed for
      eligibility. Using the full text of each publication, 2 authors independently
      followed a 2-step procedure. First, they determined that 9 studies met inclusion
      criteria. Next, they extracted data using a structured data collection form.
      Investigators were contacted for data clarification. RESULTS: All extremely
      preterm infant survivors have a substantial likelihood of developing moderate to
      severe impairment. Wide confidence intervals at the lower gestations (eg, at 22
      weeks, 43% [95% CI, 21%-69%]; heterogeneity I2, 0%) and high heterogeneity at the
      higher gestations (eg, at 25 weeks, 24% [95% CI, 17%-32%]; I2, 66%) limit the
      results. There was a statistically significant absolute decrease in moderate to
      severe impairment between each week of gestation (6.5% [95% CI, 2%-11%]).
      CONCLUSIONS AND RELEVANCE: Knowledge of these data, including the limitations,
      should facilitate discussion during the shared decision-making process about care
      plans for these infants, particularly in centers without their own data. More
      prospective, high-quality, complete cohorts are needed.

PMID- 23979323
TI  - [What did editors aim at in publication of the "Handbook"?].

PMID- 23979325
TI  - [How to utilize the handbook to contribute to a JMA's concept of healthy aging
      society].

PMID- 23979324
TI  - [Role of medical doctors in policy making for healthy longevity with reference to
      the handbook of healthy longevity medicine].

PMID- 23979326
TI  - [From the point of view of general and/or geriatric practitioner].

PMID- 23979327
TI  - [How should JGS utilize the clinical handbook for active aging?--From research
      point of view--].

PMID- 23979328
TI  - [Cognitive function and diabetes mellitus in Japanese community-dwelling elderly
      in Tosa].

PMID- 23979329
TI  - [The association between arterial stiffness and functional impairment].

PMID- 23979330
TI  - [Depression screening and possible applications of advance care planning].
AB  - Depression screening was conducted to determine the health status of community
      dwelling elderly individuals, and the concept of advance care planning was
      introduced. While depression screening among the elderly often uses the Geriatric
      Depression Scale, a single question regarding depressive mood also provides a
      valid measure of depression in elderly persons. Depression is associated with
      lower activities of daily living, competence, and subjective quality of life
      among the elderly living in Vietnam and Indonesia, as well as in Japan. Advance
      care planning is a process of discussion between individuals and their care
      providers to make decisions about future care preferences and priorities, while
      they are still capable. If they wish, they may prepare an advance directive to
      inform others about their decisions and best interests, such as a written advance
      decision to refuse treatment and/or appointment of a person with lasting powers
      of attorney. The purpose of advance care planning is to enable elderly persons to
      receive better end-of-life care. To promote introduction of advance care planning
      in Japan, voluntary discussion among family members should be encouraged. 

PMID- 23979331
TI  - [Health status of high-altitude population].
AB  - The health status of high-altitude population in Qinghai (China), Ladakh (India),
      and Arunachal (India) was investigated using comprehensive geriatric functional
      assessment in relation to their recent lifestyle change with the socio-economic
      globalization. People in urban areas had a higher prevalence of lifestyle-related
      diseases and poorer geriatric functions, and a lower subjective quality of life
      (QOL) than people in rural areas. The optimal prevention of lifestyle-related
      diseases and preservation of a high QOL are important for the people living in
      each of the above-mentioned areas with a high altitude. 

PMID- 23979332
TI  - [International comparison on diets of the elderly in community: with a focus on
      food diversity and eating behavior].

PMID- 23979333
TI  - [Association between high altitude and depression in the Himalayas and the
      Andes].
AB  - AIM: Suicide rates in the United States are higher in higher altitude areas, and
      hypoxia has been cited as a factor in these higher rates. There may be a
      significant correlation between rates of depression and altitude, but little data
      exist outside the United States. The purpose of the present study is to conduct a
      survey of depression among the elderly residing in the Himalayas and the Andes.
      METHOD: We visited Ladakh (altitude 3,800-4,800 m) in India, Qinghai (3,700 m) in
      China and Puyca (3,600 m) in Peru between July 2009 and July 2011. We recruited
      114 farmers from Domkhar in Ladakh (mean age, 69.2 years; female-male ratio,
      58.8%), 206 nomads from Changthang in Ladakh (55.1 years; 43.7%), 173 Tibetan
      subjects from Qinghai (66.5 years; 61.3%) and 103 indigenous Andean subjects from
      Puyca (69.0 years; 68.0%). The two-item Patient Health Questionnaire (PHQ-2) was
      administered to the subjects. A psychiatrist interviewed the residents with
      single or double positive scores on the PHQ-2. RESULT: The ratio of subjects with
      one or more positive score in PHQ-2 was significantly higher in Qinghai than in
      other regions. (Domkhar vs. Changthang vs. Qinghai vs. Puyca = 7.0% vs. 5.3% vs.
      36.9% vs. 15.5%, P<0.001). However, prevalence of depression by interview did not
      change in these regions. (1.8% vs. 1.9% vs. 2.3% vs. 2.9%). CONCLUSION: Despite
      the high altitude, the prevalence of depression was low in elderly highlanders in
      the Himalayas and the Andes. These results may relate to being presumed to
      related to a deep devotion to a religion and tight interpersonal networks.

PMID- 23979334
TI  - [The progress of field medicine in the Kingdom of Bhutan].

PMID- 23979335
TI  - [A request, candid advice and an order to a geriatrics doctors--nursing point of
      view--].

PMID- 23979336
TI  - [Cooperation of doctors and long-term care support specialists].

PMID- 23979337
TI  - [Challenges and future direction of collaboration between welfare and medical
      services from the perspective of the comprehensive community support center].

PMID- 23979338
TI  - [Aging research on muscle and motor neuron].

PMID- 23979339
TI  - [Clinical aspect of sarcopenia].

PMID- 23979340
TI  - [Accelerating the translation from basic research to geriatric practice:
      potentialities of supercentenarians study].

PMID- 23979341
TI  - [Current status and future of cell-based therapy for patients with cardiogenic
      cerebral embolism].
AB  - BACKGROUND AND AIM: Cerebral infarction causes permanent neurological damage.
      Recently, the intravenous administration of bone marrow-derived mononuclear cells
      has been shown to improve functional recovery through enhanced angiogenesis in an
      experimental stroke model. Based on these observations, we have started a phase
      1/2a clinical trial of cell-based therapy for patients with cardiogenic cerebral
      embolism. METHODS: The major inclusion criterion was patients in whom severe
      cerebral embolism was diagnosed (more than 9 in the NIHSS score on day 7 after
      the onset of stroke) at age 75 or younger. The patients received 25 ml (low-dose
      group, n=6) or 50 ml (high-dose group, n=6) of bone marrow aspirate on days 7-10
      after the onset of stroke. Autologous bone marrow-derived mononuclear cells were
      purified by the density gradient method and administered intravenously on the day
      of cell aspiration. The primary endpoint was safety and improvement of the NIHSS
      score compared with our historical control. RESULTS: We treated 6 patients in the
      low-dose group and 4 patients in the high-dose group. No adverse effects were
      observed and most of the patients showed a significant improvement in
      neurological function at 6 months after cell transplantation. No enrolled
      patients showed worsening of the NIHSS score at 30 days after the treatment
      compared with the NIHSS score before the treatment. CONCLUSION: Autologous bone
      marrow mononuclear cell transplantation is apparently safe and feasible, and it
      improves functional recovery.

PMID- 23979342
TI  - [Regeneration of urinary stress incontinence--application to treatment of
      intractable urinary stress incontinence of advanced age--].

PMID- 23979343
TI  - [Therapeutic angiogenesis for critical limb ischemia].

PMID- 23979344
TI  - [Association of confidence in motor function and fear of falling with physical
      ability in community-dwelling older people].
AB  - OBJECTIVE: The objective of this study was to investigate the difference of
      physical ability depending on the presence or absence of confidence in motor
      function (CIMF) and fear of falling (FOF) in independently living community
      dwelling older adults. METHODS: Participants in this study were 368 community
      dwelling older adults (mean age+/-SD, 72.2+/-5.7 years) without instrumental
      activity of daily living (IADL) problems who participated in a comprehensive
      health check-up. CIMF (existence or non-existence), FOF (existence or non
      existence), past medical history, history of a fall within the past year, and
      self-rated health were assessed by interview. Physical ability [grip strength,
      one-leg standing (OLS), maximum walking speed (MWS), and timed up & go test
      (TUG)] was also measured. RESULTS: Our results revealed significantly more older
      adults with FOF and without CIMF than expected, indicating that CIMF might be a
      component factor in FOF. Two-way ANOVA adjusted for sex and age showed main
      effects of the CIMF factor on grip strength, OLS, and TUG, indicating that these
      physical abilities are reduced in participants without CIMF, regardless of FOF.
      On the other hand, we found a main effect of the FOF factor on MWS. Logistic
      regression analysis showed that frequency of going outdoors, self-rated health,
      arthropathy, and OLS were factors associated with CIMF. CONCLUSIONS: Our results
      suggest that CIMF is a useful screening tool for older adults with potential
      problems and evaluation of intervention for health promotion in community
      dwelling older adults without IADL problems.

PMID- 23979345
TI  - [Effects of nutrition intervention for pressure ulcer patients--healing rate and
      speed of wound size and nutrition--].
AB  - The objective of this multicenter open-label randomized study was for evaluating
      nutrition intervention on pressure ulcer healing. Tube-fed patients with Stages
      III to IV pressure ulcers were enrolled. Target energy levels to be given were
      the same value as at the time of enrollment or BEE*1.1 (activity factor)*1.1-1.3
      (stress factor) in the control group, and BEE*1.1*1.3-1.5 in the intervention
      group. Both groups received the feeding formula Racol((r)) for 12 weeks, and were
      prescribed to have pressure relief mattresses, and to unify the repositioning
      method, treatment drugs, and wound dressing materials. Ulcer sizes
      (length*width), nutritional state, and adverse events were evaluated. RESULTS OF
      THE STUDY: Energy levels administered to the control (n=29) and intervention
      (n=21) groups were 29.1+/-4.9 (mean+/-SD) and 37.9+/-6.5 kcal/kg/day,
      respectively. Regarding pressure ulcer size, the interaction between the
      nutrition intervention and the courses during observational weeks was significant
      (P<0.001). Similarly, significant differences were observed with weight, waist
      circumference, Cu (P<0.001), suprailiac skinfold thickness (P<0.01), thigh
      circumference, and prealbumin (P<0.05), but not with the incidence of adverse
      events (P=0.360). Principal component analysis indicated remarkable decreases in
      ulcer size and improvement rates of waist circumference and suprailiac skinfold
      thickness in the intervention group. Covariance structure analysis showed that
      nutrition intervention has a direct effect on reduction in ulcer size. The
      results suggested that aggressive nutrient intervention accelerated the pressure
      ulcer of wound healing process and had a direct effect on reduction in ulcer
      size.

PMID- 23979346
TI  - [Leg edema detected on comprehensive geriatric assessment for elderly outpatients
      and its associated risk factors].
AB  - AIM: Leg edema, observed on comprehensive geriatric assessment (CGA) of 142
      elderly outpatients with a variety of chronic diseases, was studied clinically to
      clarify its incidence and its associated risk factors. METHODS: The severity of
      pitting edema was assessed at 3 points, namely, the pretibial edge, medial
      malleolus, and the dorsum of the foot. On palpation, edema was graded as 0 to 3
      for each point on one leg, the sum of which was used as the edema score.
      According to the edema score, subjects were divided into 3 groups; the moderate
      to severe (MS) group, the slight to mild (SM) group, and the group without
      pitting edema. The MS group was defined as having an edema score of 4 or more or
      edema of grade 2 or more, while the SM group was defined as having an edema score
      of 2 to 3 points without edema of grade 2 or more. The status of underlying
      disease, vascular risks, varicose veins, medications, daily activity, nutrition,
      total protein (TP), albumin, brain natriuretic peptide (BNP), and the estimated
      glomerular filtration rate (eGFR) were compared among the 3 groups. RESULTS:
      There were 36 subjects in the MS group and 19 subjects in the SM group. Diabetes,
      atrial fibrillation, varicose veins, and polypharmacy were more frequent in the
      MS group than in the control group. Sedentary life style, house-bound, and gait
      trouble were significantly more frequent in the MS and SM groups. There were no
      significant differences in the scores of the Mini-Nutritional Assessment Short
      Form among the groups, although both the body weight and calf circumference in
      the MS group were significantly greater than those in the group without pitting
      edema. Low serum TP, albumin and eGFR were seen in the MS group as well as high
      BNP levels. Multiple regression analysis revealed diabetes, varicose veins,
      sedentarism, and hypoalbuminemia as risk factors associated with leg edema
      (R(2)=0.365, p<0.0001). CONCLUSION: Leg edema was frequent in the elderly
      outpatients and was associated strongly with diabetes, varicose veins,
      sedentarism, and hypoalbuminemia. These findings suggest that advising against a
      sedentary life style could help the resolution of edema, and also indicates the
      clinical usefulness of CGA. Furthermore, leg edema should be seriously considered
      along with nutritional assessment because edema could influence various
      anthropometric parameters.

PMID- 23979347
TI  - [Development of a novel one-phrase screening test for early Alzheimer disease].
AB  - AIM: "Saving appearances behavior", pretending to know the correct answer, or a
      reply of deceptive replies, are often found in the reply of patients with
      dementia. We have already found that we can classify the answers to "what is the
      latest news on TV or newspapers?" into 4 types, including saving appearances
      answer. The purpose of the present study is to develop a simple clinical
      diagnostic method based on the answers to "what is the latest news on TV or
      newspapers?" for differentiating patients with Alzheimer's disease (AD) from
      those with mild cognitive impairment (MCI), and to test the validity, sensitivity
      and specificity of the method. METHODS: We recruited 133 consecutive outpatients
      with AD, 116 with MCI, and 54 normal cognitive aging controls (NC). Mini-Mental
      State Examination (MMSE) was performed for all of the subjects. Severity of
      memory disturbance was rated 0 (none) to 3 (severe) according to the results of
      the 3-object recall portion of the MMSE questionnaire. RESULTS: Only 20% of AD
      and 32% of MCI responded correctly about the recent news while 96% of NC
      responded correctly. Among patients with AD and MCI, one third of them showed
      "saving appearance behavior". Taking the result of the memory disturbance
      according to the MMSE in consideration, the present study indicates that the AD
      patients can be distinguished from MCI and NC with high sensitivity (98%) and
      high specificity (94%) using this simple, one-phrase question. CONCLUSIONS: "What
      is the latest news on TV or papers?" was highly effective in identifying AD and
      MCI. The present study suggests that the "saving appearances answer" is
      associated with the onset or awareness of memory impairment, the maintenance of
      the frontal lobe function and other characteristics of the patient.

PMID- 23979348
TI  - [A case of nonsystemic vasculitic neuropathy with spondylosis deformans in an 84
      year-old woman].
AB  - We report an 84-year-old woman with left lower limb muscle weakness and numbness
      who also had weakness in her right lower limb, which showed spontaneous partial
      improvement. Neurological examination revealed lower extremity weakness and
      sensory disturbance in all modalities, predominantly distally on the left side.
      Laboratory studies yielded normal results, except for a slightly high erythrocyte
      sedimentation rate. Nerve conduction studies showed axonal neuropathy in the
      right tibial nerve, and loss of action potentials in other lower limb nerves.
      Histological study of the left sural nerve revealed mainly loss of axons and
      differences in the density of fascicules in the axons. In addition, inflammatory
      cells infiltrated around small blood vessels. Therefore, we diagnosed nonsystemic
      vasculitic neuropathy. Magnetic resonance imaging revealed that she also had
      spondylosis deformans and radiculopathy, which was more difficult to
      differentiate. Neural biopsy was important for diagnosis. 

PMID- 23979349
TI  - [A case of elderly-onset type 1 diabetes mellitus: negative for antiglutamic acid
      dehydrogenase antibody and positive insulinoma-associated tyrosine phosphatase
      like protein-2 antibody].
AB  - An 83-year-old Japanese woman given a diagnosis of type 2 diabetes mellitus 3
      years previously was hospitalized for markedly elevated plasma glucose (386
      mg/dl) and glycated hemoglobin (9.3%) levels. Laboratory study results showed
      urinary connecting peptide immunoreactivity (CPR) concentrations of 8.9 MUg/day
      and serum CPR levels <0.2 ng/ml before and 0.3 ng/ml 6 min after glucagon
      administration, indicating decreased insulin secretion. Although antiglutamic
      acid dehydrogenase (GAD) antibody levels were negative, insulinoma-associated
      tryrosine phosphatase-like protein-2 (IA-2) antibody levels were positive (50
      U/ml), leading to a diagnosis of type 1 diabetes mellitus. Furthermore, human
      leukocyte antigen (HLA) typing revealed DRB1*0901, a diabetes-susceptibility
      gene. Intensive insulin therapy was initiated. This was a rare case of elderly
      onset type 1 diabetes.

PMID- 23979350
TI  - [An elderly woman with macrocytic anemia and acute high-output heart failure
      following acute bleeding due to a gastric ulcer].
AB  - Although macrocytic anemia can develop in patients with acute blood loss, such
      anemia in very old patients is uncommon. In this report, we describe the course
      of an 89-year-old woman who had a rapid recovery from macrocytic anemia by
      medication only after acute blood loss due to a gastric ulcer. She had been
      treated with antihypertensive drugs for the previous 28 years at our outpatient
      clinic, and was admitted because of acute anemia 6 days after she had experienced
      tarry stool. Her hemoglobin (Hb) count and mean corpuscular volume (MCV) were 8.4
      g/dl, and 103 fl, respectively. A gastroscopic examination indicated that the
      tarry stool originated from a fresh gastric ulcer. She was treated with an iron
      preparation, a diuretic and a proton pump inhibitor. The anemia was rapidly
      improved to Hb 10.5 g/dl and MCV 106 fl in one week, and to Hb 14.5 g/dl and MCV
      99 fl in 4 weeks. At admission, she had slight pleural effusion and slight edema
      associated with an increase in her plasma brain natriuretic peptide (BNP) level
      (323 pg/ml), and her left ventricular ejection fraction was 76% based on the
      echocardiography findings, which are signs of the high-output heart failure
      without remarkable left ventricular diastolic dysfunction (E/e': 11.2). However,
      these signs improved rapidly, and her BNP level thereafter decreased to 114 pg/ml
      within four weeks. 

PMID- 23979351
TI  - [Micro-debate about withdrawal of percutaneous endoscopic gastrostomy (PEG)
      feeding at end-of-life].

PMID- 23979352
TI  - Perspectives on radiation dose in abdominal imaging.
AB  - Reported instances of patients' overexposure to imaging-related radiation have
      spurred the radiology and medical physics communities to identify and develop
      methods for decreasing the amount of radiation used to achieve diagnostic-quality
      images. These initiatives include examining and optimizing conventional CT
      scanning parameters, introducing innovative scan protocols, and incorporating
      novel dose reduction technologies. The greatest challenge to effective dose
      reduction in the abdomen and pelvis remains patient size. Here, we review the
      state of the art in abdominopelvic CT in both adult and pediatric patients and
      describe some of our own efforts in dose reduction for these types of
      examinations. 

PMID- 23979353
TI  - Are there differences in LDL-C target value attainment in Austrian federal
      states? Yes!
AB  - Low density lipoprotein (LDL-C) levels determine the cardiovascular risk.
      Previous studies indicated an LDL-C target attainment of around 50%, but no
      Austrian wide analysis on results for the federal states was available. We
      therefore sought to detect potential differences. DESIGN: Open-label, non
      interventional, longitudinal study, registered: www.clinicaltrials.gov NCT
      01381679. In all, 746 statin treated patients not at LDL-C goal received
      intensified therapy for 12 months. The sample was split into nine subgroups,
      representing the federal states of Austria.We detected an east-west gradient for
      baseline LDL-C. Individual target values were achieved by 37.2% (range: 26.1
      57.7%). After 12 months, LDL-C < 70 mg/l was achieved by 13.5% (5.9-38.5%).
      Univariate ANCOVA retrieved significant differences within the states (Upper
      Austria and Salzburg, p = 0.001 and p = 0.0015, respectively). Furthermore, the
      capacity of intensified lipid lowering therapy applied in practice was as high as
      -42% as compared to previous standard therapy (additional LDL-C reduction after
      switch from baseline therapy in Vorarlberg).

PMID- 23979354
TI  - Incidental findings on cone beam computed tomography scans in cleft lip and
      palate patients.
AB  - OBJECTIVES: Cone beam computed tomography (CBCT) is frequently used in treatment
      planning for alveolar bone grafting (ABG) and orthognathic surgery in patients
      with cleft lip and palate (CLP). CBCT images may depict coincident findings. The
      aim of this study was to assess the prevalence of incidental findings on CBCT
      scans in CLP patients. SUBJECTS AND METHODS: Initial CBCTs taken from consecutive
      patients (n = 187; mean age 11.7 years, range 6.9-45) with a non-syndromic
      orofacial cleft from January 2006 until June 2012 were systematically evaluated.
      Twenty-eight patients (mean age 19.3 years, range 13.2-30.9) had been subjected
      to ABG before their first CBCT was taken; 61 patients had a CBCT before and after
      ABG. Sinuses, nasopharynx, oropharynx, throat, skull, vertebrae,
      temporomandibular joint (TMJ), maxilla and mandible were checked for incidental
      findings. RESULTS: On 95.1 % of the CBCTs, incidental findings were found. The
      most prevalent were airway/sinus findings (56.1 %), followed by dental problems,
      e.g. missing teeth (52 %), nasal septum deviation (34 %), middle ear and mastoid
      opacification, suggestive for otitis media (10 %) and (chronic) mastoiditis (9
      %), abnormal TMJ anatomy (4.9 %) and abnormal vertebral anatomy (1.6 %). In the
      28 patients whose first CBCT was taken at least 2 years after ABG, bone was still
      present in the reconstructed cleft area except in 2 out of 12 patients with a
      bilateral CLP. The ABG donor site (all bone grafts were taken from the chin area)
      was still recognizable in over 50 % of the patients. Based on the CBCT findings,
      10 % of the patients were referred for further diagnosis and 9 % for further
      treatment related to dental problems. CONCLUSION: Incidental findings are common
      on CBCTs. Compared with the literature, CLP patients have more dental, nasal and
      ear problems. Thus, whenever a CBCT is available, this scan should be reviewed by
      all specialists in the CLP team focusing on their specific background knowledge
      concerning symptoms and treatment of these patients. CLINICAL RELEVANCE: The high
      number of findings indicates that CBCT imaging is a helpful tool in the treatment
      of CLP patients not only related to alveolar bone grafting and orthognathic
      surgery but it also provides diagnostic information for almost all specialties
      involved in CLP treatment.

PMID- 23979355
TI  - Transverse charge transport through DNA oligomers in large-area molecular
      junctions.
AB  - We investigate the nature of charge transport in deoxyribonucleic acid (DNA)
      using self-assembled layers of DNA in large-area molecular junctions. A protocol
      was developed that yields dense monolayers where the DNA molecules are not
      standing upright, but are lying flat on the substrate. As a result the charge
      transport is measured not along the DNA molecules but in the transverse
      direction, across their diameter. The electrical transport data are consistent
      with the derived morphology. We demonstrate that the charge transport mechanism
      through DNA is identical to non-resonant tunneling through alkanethiols with
      identical length, classifying DNA as a dielectric. 

PMID- 23979356
TI  - A biochemical analysis linking APOBEC3A to disparate HIV-1 restriction and skin
      cancer.
AB  - Human deoxycytidine deaminase APOBEC3A (Apo3A) acts as an HIV-1 restriction
      factor in cells of myeloid lineage yet functions separately as a potent mutator
      for genomic DNA. Apo3A activity and C motif deamination specificity exhibit a
      striking dependence on pH that reflects these two distinct biological processes.
      Upon infection of macrophages, HIV-1 induces the formation of autophagosomes, and
      requires autophagosomes for replication, whereas inhibiting lysosomal fusion
      indicative of late stage autophagy. Here we show that Apo3A has optimal activity
      and a strict 5'-YYCR motif specificity in the pH 5.8-6.1 range, characteristic of
      enclosed autophagosomal membrane compartments, and reflective of the mutation
      pattern of HIV-1. In contrast to the high activity and narrow specificity of
      Apo3A at acid pH, a 13-30-fold reduction in specific activity is accompanied by
      relaxed C deamination specificity at pH 7.4-8. Notably, Apo3A is also expressed
      in keratinocytes, and is up-regulated in skin lesions. At pH 7.9, we show that
      Apo3A generates transcription-dependent CC -> TT tandem mutations on the non
      transcribed strand, a hallmark signature of skin cancer. The biochemical data
      taken in conjunction with the biological up-regulation of Apo3A in skin lesions
      suggests that enzyme-catalyzed deaminations at adjacent C sites followed by
      normal replication generating CC -> TT mutations provides an alternative
      molecular basis for the initiation events in skin cancer in contrast to well
      established pathways in which CC dimers formed in response to UV radiation either
      undergo nonenzymatic spontaneous deaminations or aberrant replication. 

PMID- 23979357
TI  - The TREX1 C-terminal region controls cellular localization through
      ubiquitination.
AB  - TREX1 is an autonomous 3'-exonuclease that degrades DNA to prevent inappropriate
      immune activation. The TREX1 protein is composed of 314 amino acids; the N
      terminal 242 amino acids contain the catalytic domain, and the C-terminal region
      (CTR) localizes TREX1 to the cytosolic compartment. In this study, we show that
      TREX1 modification by ubiquitination is controlled by a highly conserved sequence
      in the CTR to affect cellular localization. Transfection of TREX1 deletion
      constructs into human cells demonstrated that this sequence is required for
      ubiquitination at multiple lysine residues through a "non-canonical" ubiquitin
      linkage. A proteomic approach identified ubiquilin 1 as a TREX1 CTR-interacting
      protein, and this interaction was verified in vitro and in vivo. Cotransfection
      studies indicated that ubiquilin 1 localizes TREX1 to cytosolic punctate
      structures dependent upon the TREX1 CTR and lysines within the TREX1 catalytic
      core. Several TREX1 mutants linked to the autoimmune diseases Aicardi-Goutieres
      syndrome and systemic lupus erythematosus that exhibit full catalytic function
      were tested for altered ubiquitin modification and cellular localization. Our
      data show that these catalytically competent disease-causing TREX1 mutants
      exhibit differential levels of ubiquitination relative to WT TREX1, suggesting a
      novel mechanism of dysfunction. Furthermore, these differentially ubiquitinated
      disease-causing mutants also exhibit altered ubiquilin 1 co-localization. Thus,
      TREX1 post-translational modification indicates an additional mechanism by which
      mutations disrupt TREX1 biology, leading to human autoimmune disease. 

PMID- 23979358
TI  - [New indications for deep brain stimulation: ethical criteria for research and
      therapy].
AB  - The applications of deep brain stimulation (DBS) are rapidly increasing and now
      include a large variety of neurological and psychiatric diseases, such as
      depression, obsessive compulsive disorders, addiction, Alzheimer's disease,
      anorexia nervosa and rare movement disorders. These new applications confer a
      huge therapeutic potential in diseases for which often no treatment exists or
      which are refractory to existing therapies. This spread of applications, however,
      implies ethical problems in several domains: clinical use, research and
      presentation in the media and public. Thus, a systematic ethical analysis is
      needed to inform and guide this process. In this article we identify ethical
      problems involved in research and clinical use of novel DBS applications, suggest
      criteria and distinctions for structuring the ethical analysis, and articulate
      ethical demands for DBS research of novel applications. 

PMID- 23979359
TI  - [Psychiatry with open doors].

PMID- 23979360
TI  - [Verbal memory in patients with major depression].
AB  - INTRODUCTION: Patients with major depression commonly report memory deficits but
      studies on this topic have shown inconsistent results. The aim of this study was
      to determine whether patients with major depression showed any differences in
      explicit verbal memory compared to healthy controls. MATERIAL AND METHODS: We
      used the California verbal learning test (CVLT) in order to compare the explicit
      verbal memory of 30 patients (21 women and 9 men) to a healthy control group (23
      women and 10 men). RESULTS: The results showed no significant differences between
      verbal memory performance of patients with major depression and healthy controls.
      DISCUSSION: Verbal memory of depressive patients with antidepressant
      pharmacotherapy showed no significant differences compared to a healthy control
      group. It can be assumed that verbal memory in depression depends on variable
      parameters (e.g. age, severity and duration of depression and medication). More
      studies with a larger number of patients should be conducted to obtain reliable
      results about explicit verbal memory in depression.

PMID- 23979361
TI  - [Involuntary psychiatric hospital admissions: a comparison between five hospitals
      in three German federal states].
AB  - BACKGROUND: There is considerable variance in involuntary psychiatric hospital
      admission rates both in Europe and Germany. In a prospective comparison between
      five hospitals in three German federal states we assessed and analyzed
      involuntary psychiatric hospital admissions, including the patient's perspective.
      MATERIAL AND METHOD: All involuntarily admitted patients were assessed by an
      independent researcher. Clinical data, patient and psychiatrist views were
      documented with different instruments including the McArthur admission experience
      survey. RESULTS: In this study 104 out of 244 involuntarily admitted patients
      gave informed consent. We found considerable differences between study centres
      concerning involuntary admission quotas (3.2-25.8% of all hospital admissions)
      and involuntary admission rates (16.6-97.6 per year per 100,000 inhabitants).
      Hospitals in the state of Baden-Wurttemberg had the lowest involuntary admission
      rates while they were highest in Bavaria. In Baden-Wurttemberg involuntarily
      admitted patients were more likely to suffer from chronic schizophrenia, they
      were more severely ill and experienced the involuntary hospital admission as more
      strenuous. There were no differences between centres concerning frequency of
      dangerous behavior or self-harm. CONCLUSION: We found a high variance across
      regions concerning the reasons for, frequencies and legal basis of involuntary
      hospital admissions. Regional differences of legal frameworks and service
      organization can explain this only to a limited amount. Transparency, legal
      certainty and reflection of stakeholder roles are a future necessity.
      Furthermore, there is a need for stringent compliance with legal regulations and
      coherent documentation.

PMID- 23979362
TI  - [Compulsory treatment in psychiatry: an ethical analysis of the new legal
      regulations for clinical practice].
AB  - BACKGROUND: The new legal regulations of compulsory treatment in Germany require
      a change in clinical psychiatric practice as well as an ethical analysis of the
      consequences for those involved. MATERIALS AND METHODS: The new legal regulations
      are reported and via ethical analysis new problematic fields, such as
      consequences of the new law are identified and discussed in the context of
      psychiatry and law. RESULTS: The main ethical identified problems are care of
      mentally ill with mental competence who refuse medical treatment, the different
      normative assessment of compulsory treatment and mechanical fixation, the
      ambivalent role of the conversation between psychiatrist and patient in order to
      change the natural will of the patient to avoid compulsory measures, the ethical
      consequences of questionable financial incentives in the context of compulsory
      treatment and the contradictive legal regulations in the field. CONCLUSIONS: The
      ethical analysis of the new law on compulsory treatment in Germany shows chances
      for improvement of clinical psychiatric practice as well as normative problematic
      regulations and fields of conflicts.

PMID- 23979363
TI  - [Coercive measures in psychiatric clinics in Germany: current practice (2012)].
AB  - BACKGROUND: Due to the decisions of the German Constitutional Court on
      involuntary medication and the law on the prohibition of video surveillance in
      psychiatry in Nordrhine-Westfalia there has been an increasing discussion on
      coercive measures and how to conduct, supervise and prevent them. We conducted an
      online survey on the current practice of coercive measures in German psychiatric
      hospitals (2012). METHOD: An online questionnaire was developed together with the
      working group for the prevention of violence and coercion in psychiatry and the
      regional association of psychiatry-experienced people in Baden-Wuerttemberg. The
      survey was conducted anonymously using the e-mail distribution lists of the
      psychiatric associations in Germany. RESULTS: A total of 88 questionnaires from
      hospitals with obligatory responsibility for a catchment area (19.7% of those
      addressed) could be analyzed. Of these 99% used internal or external guidelines,
      97.5% conducted de-escalation training, 23% participated in external benchmarking
      on the use of coercive measures. All hospitals used mechanical restraint,
      approximately 50% seclusion and physical restraint was practiced in 7%. Most, but
      not all hospital directors reported that mechanical restraint and seclusion were
      continuously (24/7) monitored. Changes in practice in the years to come were
      expected by the majority. CONCLUSIONS: The survey revealed a high critical
      awareness concerning the use of coercive measures and the willingness to further
      change the practice.

PMID- 23979364
TI  - Carbon nanotubes reinforced chitosan films: mechanical properties and cell
      response of a novel biomaterial for cardiovascular tissue engineering.
AB  - Carbon nanotubes have been proposed as fillers to reinforce polymeric
      biomaterials for the strengthening of their structural integrity to achieve
      better biomechanical properties. In this study, a new polymeric composite
      material was introduced by incorporating various low concentrations of
      multiwalled carbon nanotubes (MWCNTs) into chitosan (CS), aiming at achieving a
      novel composite biomaterial with superior mechanical and biological properties
      compared to neat CS, in order to be used in cardiovascular tissue engineering
      applications. Both mechanical and biological characteristics in contact with the
      two relevant cell types (endothelial cells and vascular myofibroblasts) were
      studied. Regarding the mechanical behavior of MWCNT reinforced CS (MWCNT/CS), 5
      and 10 % concentrations of MWCNTs enhanced the mechanical behavior of CS, with
      that of 5 % exhibiting a superior mechanical strength compared to 10 %
      concentration and neat CS. Regarding biological properties, MWCNT/CS best
      supported proliferation of endothelial and myofibroblast cells, MWCNTs and
      MWCNT/CS caused no apoptosis and were not toxic of the examined cell types.
      Conclusively, the new material could be suitable for tissue engineering (TE) and
      particularly for cardiovascular TE applications.

PMID- 23979366
TI  - Recombinant soluble thrombomodulin as an adjunctive treatment for sepsis and
      disseminated intravascular coagulation: relatively safe and possibly effective.

PMID- 23979365
TI  - A randomized, double-blind, placebo-controlled, Phase 2b study to evaluate the
      safety and efficacy of recombinant human soluble thrombomodulin, ART-123, in
      patients with sepsis and suspected disseminated intravascular coagulation.
AB  - OBJECTIVES: To determine the safety and efficacy of recombinant thrombomodulin
      (ART-123) in patients with suspected sepsis-associated disseminated intravascular
      coagulation. DESIGN: Phase 2b, international, multicenter, double-blind,
      randomized, placebo-controlled, parallel group, screening trial. SETTING: Two
      hundred and thirty-three ICUs in 17 countries. PATIENTS: All adult patients
      admitted with sepsis and suspected disseminated intravascular coagulation as
      assessed using a modified International Society on Thrombosis and Hemostasis
      score. INTERVENTIONS: Patients were randomized to receive IV ART-123 (0.06
      mg/kg/d) for 6 days or placebo, in addition to standard of care. The primary
      endpoint was reduction in mortality. Secondary endpoints included reversal of
      overt disseminated intravascular coagulation and reduction in disease severity.
      MEASUREMENTS AND MAIN RESULTS: A total of 750 patients were randomized, nine of
      whom did not receive the allocated treatment so that 371 patients received ART
      123 and 370 received placebo. There were no meaningful differences between the
      two groups in any of the baseline variables. Twenty-eight-day mortality was 17.8%
      in the ART-123 group and 21.6% in the placebo group (Cochran-Mantel-Haenszel two
      sided p value of 0.273 in favor of ART-123, which met the predefined statistical
      test for evidence suggestive of efficacy). There were no statistically
      significant differences in event-free and alive days between the two groups. d
      dimer, prothrombin fragment F1.2 and TATc concentrations were lower in the ART
      123 group than in the placebo group. There were no differences between the two
      groups in organ function, inflammatory markers, bleeding or thrombotic events or
      in the development of new infections. In post hoc analyses, greatest benefit from
      ART-123 was seen in patients with at least one organ system dysfunction and an
      international normalized ratio greater than 1.4 at baseline. CONCLUSIONS: ART-123
      is a safe intervention in critically ill patients with sepsis and suspected
      disseminated intravascular coagulation. The study provided evidence suggestive of
      efficacy supporting further development of this drug in sepsis-associated
      coagulopathy including disseminated intravascular coagulation. Future study
      should focus on using ART-123 in the subgroup of patients most likely to respond
      to this agent.

PMID- 23979367
TI  - Systemic inflammation after myocardial infarction.

PMID- 23979368
TI  - Time to recommend heparin and low-molecular-weight heparins in thromboprophylaxis
      in medical-surgical critically ill patients.

PMID- 23979369
TI  - Cooperative approach: a further step in antimicrobial stewardship programs.

PMID- 23979370
TI  - Protecting both heart and brain: a noble goal for a noble gas.

PMID- 23979371
TI  - A new purpose for proportional assist ventilation?

PMID- 23979372
TI  - Hospital-acquired pneumonia: is culture negativity associated with better
      survival?

PMID- 23979373
TI  - The (pulmonary) Watergate revisited.

PMID- 23979374
TI  - Adverse outcomes in intensive care-acquired pneumonia are important to predict.

PMID- 23979375
TI  - Beta-1 blockade in sepsis: what to expect?

PMID- 23979376
TI  - Prognostic value of enterocyte injury in critically ill patients: no gut, no
      glory?

PMID- 23979377
TI  - Patient-ventilator asynchrony: adapt the ventilator, not the patient!

PMID- 23979378
TI  - Sodium bicarbonate--the swings and roundabouts will not stop without randomized
      evidence.

PMID- 23979379
TI  - Blood purification: can we purify our patients from sepsis?

PMID- 23979380
TI  - Mast cells and intestinal injury: a novel link between hypoxia and inflammation.

PMID- 23979381
TI  - The cool bypass toward life: hypothermic extracorporeal membrane oxygenation
      after cardiac arrest.

PMID- 23979382
TI  - Disturbing the programmed cell death.

PMID- 23979383
TI  - Rescue therapy with noninvasive ventilation in do-not-intubate patients in acute
      respiratory failure: what is the best device among face masks?

PMID- 23979384
TI  - The authors reply.

PMID- 23979385
TI  - Institutional and national MEDMARX data have differences in causes and types of
      medication errors but agree on the higher propensity for harm in the ICU.

PMID- 23979386
TI  - The authors reply.

PMID- 23979387
TI  - Delirium--a further complication for patients undergoing heart surgery?

PMID- 23979388
TI  - The authors reply.

PMID- 23979389
TI  - A semantic point of view about unstressed blood volume.

PMID- 23979390
TI  - The authors reply.

PMID- 23979391
TI  - The risk of catheter-related bloodstream infection in different catheter
      insertion sites: evidence versus guidelines.

PMID- 23979392
TI  - The author replies.

PMID- 23979393
TI  - The association between severity of acute lung injury and use of sedative.

PMID- 23979394
TI  - The authors reply.

PMID- 23979395
TI  - Beta-blockers and acute kidney injury in patients with ST-segment elevation
      myocardial infarction.

PMID- 23979396
TI  - The author replies.

PMID- 23979397
TI  - Production of diabetic offspring using cryopreserved epididymal sperm by in vitro
      fertilization and intrafallopian insemination techniques in transgenic pigs.
AB  - Somatic cell nuclear transfer (SCNT) is a useful technique for creating pig
      strains that model human diseases. However, production of numerous cloned disease
      model pigs by SCNT for large-scale experiments is impractical due to its
      complexity and inefficiency. In the present study, we aimed to establish an
      efficient procedure for proliferating the diabetes model pig carrying the mutant
      human hepatocyte nuclear factor-1alpha gene. A founder diabetes transgenic cloned
      pig was generated by SCNT and treated with insulin to allow for normal growth to
      maturity, at which point epididymal sperm could be collected for
      cryopreservation. In vitro fertilization and intrafallopian insemination using
      the cryopreserved epididymal sperm resulted in diabetes model transgenic
      offspring. These results suggest that artificial reproductive technology using
      cryopreserved epididymal sperm could be a practical option for proliferation of
      genetically modified disease model pigs. 

PMID- 23979398
TI  - Assessment of fine needle aspiration cytology samples for molecular genetic
      analysis in neuroblastoma.
AB  - PURPOSE: To assess the utility of fine needle aspiration cytology (FNAC) samples
      for molecular genetic analysis of neuroblastoma. METHODS: The case files from the
      pediatric solid tumor clinic were reviewed to identify 20 neuroblastoma patients
      whose pre-treatment FNAC slides were preserved in the cytology laboratory. The
      FNAC slides were destained, air dried and hybridisation with fluorescence in situ
      hybridisation (FISH) probes was performed as per protocol. All slides were
      screened and analyzed carefully under the fluorescent microscope. Over four-fold
      increase of the N-myc signal numbers was defined as N-myc amplification. Focal
      occurrence of cells (at least 50) showing N-myc amplification surrounded by non
      amplified tumor cells was defined as focal N-myc amplification. Presence of three
      or more signals for the long arm of chromosome 17 was defined as 17q gain.
      RESULTS: FISH analysis gave informative results for all the FNAC smears in our
      study. FISH analysis of FNAC smears showed N-myc amplification in 5 (25 %) out of
      20 patients and 15 (75 %) showed normal N-myc copy number. Three out of these
      five patients had homogenous amplification and two patients had focal N-myc
      amplification, indicating tumor heterogeneity. On investigation of chromosome 17q
      status, 5 (25 %) out of 20 patients demonstrated gain of 17q and 15 (75 %)
      patients showed normal 17q status. Four out of the five patients with 17q gain
      also showed N-myc amplification. CONCLUSIONS: The current study indicates that
      FNAC is a rapid and atraumatic diagnostic method for neuroblastoma which provides
      sufficient material for molecular genetic analyses by means of FISH.

PMID- 23979399
TI  - The efficacy of double-balloon enteroscopy for intrahepatic bile duct stones
      after Roux-en-Y hepaticojejunostomy for choledochal cysts.
AB  - INTRODUCTION: Intrahepatic bile duct (IHBD) stones are one of the most
      complicated morbidities that occur after Roux-en-Y hepaticojejunostomy (RYH);
      however, the optimal therapeutic approach is controversial. METHODS: Double
      balloon enteroscopy (DBE) has been widely and frequently performed even in
      pediatric patients. We herein report the successful management of IHBD stones by
      biliary lithotripsy using DBE after RYH for a choledochal cyst (CC). DBE has made
      it possible to perform endoscopic therapeutic intervention, including balloon
      dilatation of an anastomotic stricture and removal of IHBD stones, without any
      major complications. CONCLUSION: DBE is a less invasive and safe treatment method
      for IHBD stones in pediatric patients, which is capable of reaching the
      bilioenteric anastomosis after RYH for CC.

PMID- 23979400
TI  - Surgical intervention for congenital diaphragmatic hernia: open versus
      thoracoscopic surgery.
AB  - PURPOSE: To compare open repair (OR) with thoracoscopic repair (TR) for
      congenital diaphragmatic hernia (CDH) in neonates. METHODS: Twenty-four neonatal
      CDH cases diagnosed prenatally or within 6 h of birth at our institute from 2002
      to 2012 with mild pulmonary hypertension managed without inhaled nitric oxide,
      were studied. OR was routine until 2006 (n = 14; L:R = 12:2) and TR became
      routine in 2007 (n = 10; L:R = 10:0). All subjects had identical management.
      RESULTS: Gestational age at birth: OR 37.4 +/- 1.6 vs. TR: 38.3 +/- 1.1 weeks (p
      = 0.10); birth weight 2,636 +/- 490 vs. 2,887 +/- 429 grams (p = 0.20);
      preoperative A-aDO(2): 308 +/- 200 vs. 331 +/- 195 mmHg (p = 0.79); and operating
      time (min): 161 +/- 42 vs. 194 +/- 76 (p = 0.27). In TR, intraoperative
      cardiopulmonary status was stable, intraoperative hemorrhage was significantly
      less (4.8 +/- 6.0 vs. 1.1 +/- 0.1 grams; p = 0.038), wound cosmesis was excellent
      without surgical site infections, while, maximum postoperative CRP (2.0 +/- 1.5
      vs. 1.5 +/- 1.1 mg/dL; p = 0.30), commencement of enteral feeding (6.9 +/- 2.8
      vs. 5.6 +/- 2.8 days; p = 0.27), and length of postoperative hospitalization (36
      +/- 22 vs. 34 +/- 12 days; p = 0.66) were improved, but not significantly. One OR
      case required surgery for intestinal obstruction. CONCLUSIONS: Thoracoscopic
      repair appears to be as effective as OR for treating selected cases of CDH in
      neonates, with excellent wound cosmesis.

PMID- 23979401
TI  - Pulmonary FGF-18 gene expression is downregulated during the canalicular-saccular
      stages in nitrofen-induced hypoplastic lungs.
AB  - PURPOSE: Pulmonary hypoplasia (PH) associated with congenital diaphragmatic
      hernia (CDH) represents one of the major challenges in neonatal intensive care.
      However, the molecular pathogenesis of PH is still poorly understood. In
      developing fetal lungs, fibroblast growth factor 18 (FGF-18) plays a crucial role
      in distal airway maturation. FGF-18 knockouts show smaller lung sizes with
      reduced alveolar spaces and thicker interstitial mesenchymal compartments,
      highlighting its important function for fetal lung growth and differentiation. We
      hypothesized that pulmonary FGF-18 gene expression is downregulated during late
      gestation in nitrofen-induced hypoplastic lungs. METHODS: Pregnant rats were
      exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetuses were
      harvested on D18 and D21, and lungs were divided into three groups: controls,
      hypoplastic lungs without CDH [CDH(-)], and hypoplastic lungs with CDH [CDH(+)]
      (n = 24 at each time-point). Pulmonary FGF-18 gene expression levels were
      analyzed by qRT-PCR. Immunohistochemistry was performed to investigate FGF-18
      protein expression/distribution. RESULTS: Relative mRNA levels of pulmonary FGF
      18 gene expression were significantly decreased in CDH(-) and CDH(+) on D18 and
      D21 compared to controls (p < 0.05 and p < 0.01, respectively). Immunoreactivity
      of FGF-18 was markedly diminished in mesenchymal cells surrounding the airway
      epithelium on D18 and D21 compared to controls. CONCLUSION: Downregulation of FGF
      18 gene expression in nitrofen-induced hypoplastic lungs suggests that decreased
      FGF-18 expression during the canalicular-saccular stages may interfere with
      saccular-alveolar differentiation and distal airway maturation resulting in PH.

PMID- 23979402
TI  - Laminin-1 promotes enteric nervous system development in mouse embryo.
AB  - BACKGROUND/AIM: Neuronal development is regulated by extracellular environmental
      factors including nerve growth factor (NGF) and laminin. We have previously
      demonstrated that laminin-1 promotes neurite outgrowth of dorsal root ganglion
      cells by modulating NGF and integrin signaling. However, information about their
      effects on the enteric nervous system (ENS) is limited. Recently, we succeeded in
      visualizing enteric neural crest-derived cell (ENCC) migration using SOX10-Venus
      transgenic mice, in which ENCC are labeled with a green fluorescent protein,
      Venus. In this study, we examine the effects of NGF and laminin-1 in ENCC
      migration using SOX10-Venus mice gut. METHODS: Pregnant SOX10-Venus mice were
      killed on day 12.5 of gestation. The colorectum was dissected from embryos (n =
      10) and placed in culture medium including NGF with or without laminin-1 for 12
      h. Extension rates of ENCC migration, colorectum and ENCC migration per
      colorectum were calculated. RESULTS: Venus positive-ENCC extension rate was
      significantly higher in the laminin group (n = 5) compared to control (n = 5),
      22.84 and 13.96 %, respectively (p < 0.05). The extension rate of the colorectum
      was not significantly different between the two groups. CONCLUSIONS: Our results
      suggest that laminin promotes ENCC migration in mice. This technique allowed us
      to visualize the effects of extracellular molecules on ENCC migration and it
      potentially provides us with an insight into the pathophysiology of developmental
      disorders of the ENS, such as Hirschsprung's disease.

PMID- 23979403
TI  - Management of laryngotracheal stenosis in infants and children: the role of re-do
      surgery in cases of severe subglottic stenosis.
AB  - Although many advances have improved the treatment of congenital and acquired
      laryngotracheal stenosis in children over the past two decades, the therapeutic
      decision-making process remains challenging for pediatric surgeons and
      otolaryngologists. Severe subglottic stenosis is a complex laryngeal injury that
      necessitates multiple airway procedures, and the approach depends on the exact
      nature of the cicatricial lesion and its effect on the vocal cord mobility.
      Therefore, it is imperative that the pediatric surgeons and otolaryngologists
      dealing with this situation should be well trained in endoscopy and laser
      treatment, in addition to open surgical intervention. Open re-do surgery remains
      the best choice in cases of severe congenital stenosis, glottic immobility, or
      after two to three endoscopic procedures have been performed without any
      significant improvement. 

PMID- 23979404
TI  - Imidazolium salts and their polymeric materials for biological applications.
AB  - Imidazolium salts, distinct from their parent imidazoles, are made up of a
      discrete cation and anion pair, and have found widespread utility as ionic
      liquids. A lesser known function of such imidazolium salts includes the
      application of these salts in biological systems, and several areas of bio
      applications, including antitumour, antimicrobial, antioxidant and bioengineering
      applications, will be presented and discussed in this review. The wide-ranging
      applications and versatility of these imidazolium salts stem from the ease of
      their structural variation, in which properties such as amphiphilicity,
      lipophilicity and solubility can be tuned. 

PMID- 23979405
TI  - Lymphoid aggregates in Crohn's colitis and mucosal immunity.
AB  - Under normal conditions, the colorectal mucosa exhibits small numbers of
      scattered lymphocytes and plasma cells in the lamina propria and only few mucosal
      lymphoid aggregates (MLAs). In Crohn's colitis, the number of lymphocytes and
      plasma cells in the lamina propria and of MLA is substantially increased. In
      addition, multiple lymphoid aggregates are newly formed in the submucosa
      (submucosal lymphoid aggregate (SLA)) and deeper. The aim of the present study
      was to investigate the cellular immune response in MLA, in SLA, and in the lamina
      propria in Crohn's colitis. Fifty-nine colorectal biopsies/surgical specimens
      with or without inflammatory diseases were challenged with multiple myeloma 1
      (MUM1) that highlights activated T cells, committed B cells, and plasma cells
      (aT/cB/PC). The number of MUM1-positive aT/cB/PC per high-power field (HPF) in
      MLA and in SLA was significantly lower in Crohn's colitis than in controls (p <
      0.05). In contrast, the number of MUM1-positive aT/cB/PC per HPF in the lamina
      propria was significantly higher in Crohn's colitis and in other forms of chronic
      colitis than in controls (p < 0.05). The paucity of MUM1-positive cells in MLA
      and in SLA in Crohn's colitis might be caused by an increased number of MUM1
      negative precursors. These precursors would eventually migrate into the lamina
      propria to differentiate into aT/cB/PC, complying thereby with the immunological
      mucosal demands generated by the on-going chronic inflammation.

PMID- 23979406
TI  - Increased expression of Trop2 correlates with poor survival in extranodal NK/T
      cell lymphoma, nasal type.
AB  - Human trophoblastic cell surface antigen 2 (Trop2) has been suggested to play an
      important role in the development of solid tumors. However, the expression of
      Trop2 in extranodal NK/T cell lymphoma, nasal type (ENKTL) and the relationship
      with the clinical characteristics of this disease remain poorly understood. In
      this study, one-step quantitative PCR reverse transcription-polymerase chain
      reaction and immunohistochemical staining with tissue sections were employed to
      evaluate the expression of Trop2 in ENKTL. Furthermore, the relationship between
      Trop2 expression and prognosis of ENKTL was investigated. Expression of Trop2
      mRNA and protein was significantly higher in ENKTL tissue than in corresponding
      non-lymphomatous tissue (p = 0.04 and p < 0.001, respectively). Expression of
      Trop2 protein in ENKTL was associated with lymph node involvement and poor
      overall survival (p = 0.045 and p = 0.018, respectively). Kaplan-Meier analysis
      and the logrank test indicated that lymph node involvement (p = 0.0481), single
      therapy strategy (p = 0.0037), and high expression of Trop2 (p = 0.0042) are
      significantly correlated with poor prognosis of ENKTL patients. The data suggest
      that Trop2 expression reflects a more malignant phenotype and may serve as an
      unfavorable prognostic factor for ENKTL.

PMID- 23979407
TI  - Neuroendocrine carcinoma in a mediastinal teratoma as a rare variant of somatic
      type malignancy.
AB  - Somatic-type malignancy (STM), defined as any sarcoma, carcinoma, leukemia or
      lymphoma developing in a germ cell tumor, occurs in approximately 2% of all germ
      cell tumors. Neuroendocrine carcinoma developing in a mediastinal germ cell tumor
      has not been previously reported. We here describe a 22-year-old man who
      underwent resection of a 11-cm mediastinal teratoma which consisted of components
      of all three germ cell layers with prominent foci of fetal-like liver tissue. The
      liver areas were surrounded by primitive neuroendocrine structures with ductal
      and solid growth pattern with a high proliferation rate. We diagnosed an immature
      mediastinal teratoma with STM, specifically neuroendocrine carcinoma arising in a
      background of immature liver tissue. Comparative genomic hybridization of
      dissected tumor tissue revealed chromosomal gains at 12 in the teratoma and
      neuroendocrine carcinoma component. In summary, clinicians and pathologists
      should be aware of neuroendocrine carcinoma as a rare type of STM complicating
      mediastinal germ cell tumors.

PMID- 23979408
TI  - Navigating new territories in compounding for veterinary medicine.

PMID- 23979409
TI  - Total parenteral nutrition for animals.

PMID- 23979410
TI  - Veterinary Compounding for Hyperadrenocorticism (Cushing's Disease) in Dogs.

PMID- 23979411
TI  - Drug therapy for acute and chronic pain in the cat.

PMID- 23979412
TI  - Transdermal methimazole in the treatment of 16 cats with hyperthyroidism.

PMID- 23979414
TI  - Third-party contracting for compounding pharmacies.

PMID- 23979413
TI  - Quality in pharmacy: the new zealand experience.

PMID- 23979415
TI  - Basics of compounding: phonophoresis.

PMID- 23979417
TI  - Custom-compounded micronized hormones in a slow-release capsule matrix.

PMID- 23979416
TI  - Satisfaction of patients using bioidentical hormones for hormone replacement
      therapy.

PMID- 23979418
TI  - Stability of lidocaine hydrochloride injection at ambient temperature and 4 deg C
      in polypropylene syringes.
AB  - The stability of 20mg/mL lidocaine hydrochloride injection in 12-mL polypropylene
      syringes stored at ambient temperature and at 4 deg C for up to 90 days was
      investigated. A high-performance liquid-chromatographic stability-indicating
      assay was used to determine the concentration level of lidocaine hydrochloride
      injection at 0, 1, 4, 7, 15, 30, 45, 60, and 90 days after preparation of the
      syringes. Methylparaben, which was added as a preservative, did not interfere
      with the assay. The injections in plastic syringes were stable for up to 90 days
      at both ambient temperature and at 4 deg C. The pH of lidocaine hydrochloride
      injection did not change appreciable during the 90-day study period. These data
      indicate the stability of lidocaine hydrochloride under the storage conditions
      investigated in this study. 

PMID- 23979419
TI  - Effect of freezing, long-term storage, and microwave thawing on the stability of
      cefepime in 5% dextrose infusion polyvinyl chloride bags.
AB  - Cefepime is often used in antibiotic infusions for the hospitalized patients.
      Using intravenous solutions of cefepime prepared in advance can be efficient, but
      little information is available about the stability of that antibiotic after
      freezing followed by microwave thawing. The purpose of this study was to
      investigate how freezing, long-term storage, and microwave thawing can affect the
      stability of cefepime in 5% dextrose injection. The stability of 5 polyvinyl
      chloride bags of solution containing 2g of cefepime per 100 mL of 5% dextrose
      injection was studied after the bags had remained frozen for 1 month at -20 deg
      C, were thawed in a microwave oven with a validated cycle, and were stored at 4
      deg C. The concentration of cefepime was measured by high-performance liquid
      chromatography by means of a reversed phase column, a mobile phase consisting of
      10% acetonitrile and pentane sulfate buffer, and ultraviolet detection at 254 nm
      with a diode array detecor. Visual inspection was also conducted, and pH
      measurements were obtained. No color change or precipitation in the solution was
      observed. Cefepime remained stable for 11 days. During this period, the 95% lower
      confidence limit of the estimated regression line of the concentration-time
      profile remained above 90% of the initial concentration and the pH value
      increased slightly without affecting chromatographic parameters. Within those
      limits, cefepime may be prepared in advance by a centralized intravenous
      admixture service; it may be frozen and then thawed in a microwave before use in
      clinical units. 

PMID- 23979420
TI  - Chemical stability of dexamethasone sodium phosphate after reconstitution in 0.9%
      sodium chloride injection and storage in polypropylene syringes.
AB  - The chemical stability of dexamethasone sodium phosphate (1mg/mL and 0.1 mg/mL)
      in 0.9% sodium chloride injection was studied at 25 deg C in polypropylene
      syringes by means of a stability-indicating high-performance liquid
      chromatographic assay method. The concentrations of the drug were directly
      related to peak heights, and the percent relative standard deviation based on 5
      injections was 1.5. The benzyl alcohol did not interfere with the assay procedure
      at 278 nm. The products of decomposition separated from the intact drug. At a
      concentration of 1mg/mL, the loss in potency was 1% after 22 days of storage and
      less than 3% at a concentration of 0.1mg/mL after storage for 22 days. The pH
      value of the injection (1mg/mL) decreased from 7.3 to 7.2 after 22 days of
      storage and from 6.5 to 6.3 in the 0.1-mg/mL sample. The physical appearance of
      the injection did not change. 

PMID- 23979422
TI  - Delta opioid receptor and its peptide: a receptor-ligand neuroprotection.
AB  - In pursuit of neurological therapies, the opioid system, specifically delta
      opioid receptors and delta opioid peptides, demonstrates promising therapeutic
      potential for stroke, Parkinson's disease, and other degenerative neurological
      conditions. Recent studies offer strong evidence in support of the therapeutic
      use of delta opioid receptors, and provide insights into the underlying
      mechanisms of action. Delta opioid receptors have been shown to confer protective
      effects by mediating ionic homeostasis and activating endogenous neuroprotective
      pathways. Additionally, delta opioid agonists such as (D-Ala 2, D-Leu 5)
      enkephalin (DADLE) have been shown to decrease apoptosis and promote neuronal
      survival. In its entirety, the delta opioid system represents a promising target
      for neural therapies. 

PMID- 23979423
TI  - Statistical mechanical treatments of protein amyloid formation.
AB  - Protein aggregation is an important field of investigation because it is closely
      related to the problem of neurodegenerative diseases, to the development of
      biomaterials, and to the growth of cellular structures such as cyto-skeleton.
      Self-aggregation of protein amyloids, for example, is a complicated process
      involving many species and levels of structures. This complexity, however, can be
      dealt with using statistical mechanical tools, such as free energies, partition
      functions, and transfer matrices. In this article, we review general strategies
      for studying protein aggregation using statistical mechanical approaches and show
      that canonical and grand canonical ensembles can be used in such approaches. The
      grand canonical approach is particularly convenient since competing pathways of
      assembly and dis-assembly can be considered simultaneously. Another advantage of
      using statistical mechanics is that numerically exact solutions can be obtained
      for all of the thermodynamic properties of fibrils, such as the amount of fibrils
      formed, as a function of initial protein concentration. Furthermore, statistical
      mechanics models can be used to fit experimental data when they are available for
      comparison. 

PMID- 23979421
TI  - Emerging roles of small Epstein-Barr virus derived non-coding RNAs in epithelial
      malignancy.
AB  - Latent Epstein-Barr virus (EBV) infection is an etiological factor in the
      progression of several human epithelial malignancies such as nasopharyngeal
      carcinoma (NPC) and a subset of gastric carcinoma. Reports have shown that EBV
      produces several viral oncoproteins, yet their pathological roles in
      carcinogenesis are not fully elucidated. Studies on the recently discovered of
      EBV-encoded microRNAs (ebv-miRNAs) showed that these small molecules function as
      post-transcriptional gene regulators and may play a role in the carcinogenesis
      process. In NPC and EBV positive gastric carcinoma (EBVaGC), 22 viral miRNAs
      which are located in the long alternative splicing EBV transcripts, named BamH1 A
      rightward transcripts (BARTs), are abundantly expressed. The importance of
      several miR-BARTs in carcinogenesis has recently been demonstrated. These novel
      findings enhance our understanding of the oncogenic properties of EBV and may
      lead to a more effective design of therapeutic regimens to combat EBV-associated
      malignancies. This article will review the pathological roles of miR-BARTs in
      modulating the expression of cancer-related genes in both host and viral genomes.
      The expression of other small non-coding RNAs in NPC and the expression pattern
      of miR-BARTs in rare EBV-associated epithelial cancers will also be discussed. 

PMID- 23979424
TI  - Adenoviral transduction of naive CD4 T cells to study Treg differentiation.
AB  - Regulatory T cells (Tregs) are essential to provide immune tolerance to self as
      well as to certain foreign antigens. Tregs can be generated from naive CD4 T
      cells in vitro with TCR- and co-stimulation in the presence of TGFbeta and IL-2.
      This bears enormous potential for future therapies, however, the molecules and
      signaling pathways that control differentiation are largely unknown. Primary T
      cells can be manipulated through ectopic gene expression, but common methods fail
      to target the most important naive state of the T cell prior to primary antigen
      recognition. Here, we provide a protocol to express ectopic genes in naive CD4 T
      cells in vitro before inducing Treg differentiation. It applies transduction with
      the replication-deficient adenovirus and explains its generation and production.
      The adenovirus can take up large inserts (up to 7 kb) and can be equipped with
      promoters to achieve high and transient overexpression in T cells. It effectively
      transduces naive mouse T cells if they express a transgenic Coxsackie adenovirus
      receptor (CAR). Importantly, after infection the T cells remain naive (CD44(low),
      CD62L(high)) and resting (CD25(-), CD69(-)) and can be activated and
      differentiated into Tregs similar to non-infected cells. Thus, this method
      enables manipulation of CD4 T cell differentiation from its very beginning. It
      ensures that ectopic gene expression is already in place when early signaling
      events of the initial TCR stimulation induces cellular changes that eventually
      lead into Treg differentiation.

PMID- 23979425
TI  - Expression of autophagy and UPR genes in the developing brain during ethanol
      sensitive and resistant periods.
AB  - Fetal alcohol spectrum disorders (FASD) results from ethanol exposure to the
      developing fetus and is the leading cause of mental retardation. FASD is
      associated with a broad range of neurobehavioral deficits which may be mediated
      by ethanol-induced neurodegeneration in the developing brain. An immature brain
      is more susceptible to ethanol neurotoxicity. We hypothesize that the enhanced
      sensitivity of the immature brain to ethanol is due to a limited capacity to
      alleviate cellular stress. Using a third trimester equivalent mouse model of
      ethanol exposure, we demonstrated that subcutaneous injection of ethanol induced
      a wide-spread neuroapoptosis in postnatal day 4 (PD4) C57BL/6 mice, but had
      little effect on the brain of PD12 mice. We analyzed the expression profile of
      genes regulating apoptosis, and the pathways of ER stress response (also known as
      unfolded protein response, UPR) and autophagy during these ethanol-sensitive and
      resistant periods (PD4 versus PD12) using PCR microarray. The expression of pro
      apoptotic genes, such as caspase-3, was much higher on PD4 than PD12; in
      contrast, the expression of genes that regulate UPR and autophagy, such as atf6,
      atg4, atg9, atg10, beclin1, bnip3, cebpb, ctsb, ctsd, ctss, grp78, ire1alpha,
      lamp, lc3 perk, pik3c3, and sqstm1 was significantly higher on PD12 than PD4.
      These results suggest that the vulnerability of the immature brain to ethanol
      could result from high expression of pro-apoptotic proteins and a deficiency in
      the stress responsive system, such as UPR and autophagy. 

PMID- 23979426
TI  - Advanced glycation end products suppress lysyl oxidase and induce bone collagen
      degradation in a rat model of renal osteodystrophy.
AB  - Renal osteodystrophy (ROD) is a major problem in patients with renal
      insufficiency. The present study was designed to elucidate the role of bone
      collagen changes and osteoblast differentiation in a rat model of ROD
      pathogenesis induced by adenine. Typical characteristics of renal failure,
      including increased serum urea nitrogen, creatinine, inorganic phosphorus, and
      intact parathyroid hormone levels, and decreased serum calcium and 1,25(OH)2D3
      levels, were observed in adenine-induced rats. Micro-computed tomography analysis
      of the femur in adenine-induced rats showed decreased bone mineral density and
      osteoporotic changes, confirmed by the three-point bending test. The cancellous
      bone histomorphometric parameters of the tibia showed increased osteoblast
      number, decreased osteoclast surface with peritrabecular fibrosis, and increased
      osteoid tissue, indicating a severe mineralization disorder similar to clinical
      ROD. Scanning and transmission electron microscopy revealed irregular alignment
      and increased diameter of bone collagen fibrils in adenine-induced rats. Protein
      expression analysis showed greater accumulation of advanced glycation end
      products (AGEs) in peritrabecular osteoblasts of adenine-induced rats than in the
      controls. In contrast, suppressed expression of runt-related transcription factor
      2, alkaline phosphatase, secreted phosphoprotein 1 (Spp1), and lysyl oxidase
      (Lox) mRNA levels, particularly the amount of active LOX protein, were observed.
      In in-vitro experiments, mineralizing MC3T3-E1 osteoblastic cells stimulated with
      AGE-modified bovine serum albumin had attenuated the expression of Spp1 mRNA
      levels and active LOX protein, with a decrease in extracellular nodules of
      mineralization. These observations provide clues to ROD pathogenesis, as they
      indicate that the suppression of osteoblast differentiation and decreased active
      LOX protein associated with accumulation of AGEs in osteoblasts caused structural
      abnormalities of bone collagen fibrils and a severe mineralization disorder,
      leading to bone fragility. 

PMID- 23979427
TI  - Role of survivin in acute lung injury: epithelial cells of mice and humans.
AB  - Survivin, an inhibitor of apoptosis, regulates cell division and is a potential
      target for anticancer drugs because many cancers express high survivin levels.
      However, whether survivin would be toxic to human lung cells and tissues has not
      been determined. This report clarified the involvement of survivin in acute lung
      injury. We used immunohistochemical analysis, immunoelectron microscopy, and real
      time reverse transcription-quantitative polymerase chain reaction to study
      survivin expression and localization in injured mouse and human lungs. We also
      used cultured human lung epithelial cells (BEAS-2B and A549) to study survivin
      cytoprotection. Nuclei and cytoplasm of epithelial cells in day 3 and day 7
      models of bleomycin-injured lung showed survivin-positive results, which is
      consistent with upregulated survivin mRNA expression. These nuclei also evidenced
      double positive findings for proliferating cell nuclear antigen and survivin. Day
      7 models had similar Smac/DIABLO-positive and survivin-positive cell
      distributions. The cytoplasm and nuclei of epithelial cells in lesions with
      diffuse alveolar damage manifested strong survivin-positive findings. Bleomycin
      stimulation in both epithelial cell lines upregulated expression of survivin and
      apoptosis-related molecules. Suppression of survivin expression with small
      interfering RNA rendered human lung epithelial cells susceptible to bleomycin
      induced damage, with markedly upregulated activation of caspase-3, caspase-7,
      poly (ADP-ribose) polymerase, and lactate dehydrogenase activity and an increased
      number of dead cells compared with mock small interfering RNA-treated cells.
      Overexpression of survivin via transfection resulted in these epithelial cells
      being resistant to bleomycin-induced cell damage, with reduced activation of
      apoptosis-related molecules and lactate dehydrogenase activity and fewer dead
      cells compared with results for mock-transfected cells. Survivin, acting at the
      epithelial cell level that depends partly on apoptosis inhibition, is therefore a
      key mediator of cytoprotection in acute lung injury. Understanding the precise
      role of survivin in normal lung cells is required for the development of
      therapeutic survivin. 

PMID- 23979429
TI  - Bacterial physiology: coping with stress the C. crescentus way.

PMID- 23979430
TI  - Symbiosis: breaking the ice with your host.

PMID- 23979428
TI  - MLST revisited: the gene-by-gene approach to bacterial genomics.
AB  - Multilocus sequence typing (MLST) was proposed in 1998 as a portable sequence
      based method for identifying clonal relationships among bacteria. Today, in the
      whole-genome era of microbiology, the need for systematic, standardized
      descriptions of bacterial genotypic variation remains a priority. Here, to meet
      this need, we draw on the successes of MLST and 16S rRNA gene sequencing to
      propose a hierarchical gene-by-gene approach that reflects functional and
      evolutionary relationships and catalogues bacteria 'from domain to strain'. Our
      gene-based typing approach using online platforms such as the Bacterial Isolate
      Genome Sequence Database (BIGSdb) allows the scalable organization and analysis
      of whole-genome sequence data.

PMID- 23979431
TI  - What has high-throughput sequencing ever done for us?
AB  - This month's Genome Watch looks back over the past 10 years and highlights how
      the incredible advances in sequencing technologies have transformed research into
      microbial genomes. 

PMID- 23979433
TI  - Bacterial physiology: a raincoat for Bacillus subtilis.

PMID- 23979434
TI  - Protective effect of amifostine on high-dose methotrexate-induced small
      intestinal mucositis in mice.
AB  - BACKGROUND: Amifostine has been shown to be capable of minimizing radiotherapy
      induced oral mucositis, but whether it protects small intestinal mucosae from
      high-dose methotrexate-induced damage is presently unknown. AIM: We aimed to
      evaluate the protective effect of amifostine against high-dose methotrexate
      induced small intestinal mucositis and its mechanism. METHODS: Ninety Kunming
      mice were randomly divided into five experimental groups: saline control; high
      dose methotrexate (HDMTX) group: treated with a single high dose of methotrexate;
      calcium folinate (CF) group: treated with high-dose methotrexate followed with
      CF; Amifostine group: treated with amifostine, followed with high-dose
      methotrexate; and amifostine-CF group: treated with amifostine pre-high-dose
      methotrexate and followed by CF post-high-dose methotrexate. Mouse weight, villus
      height and crypt depth, stool consistency, white blood cell count, death and
      survival were recorded. Bax and Bcl-2 mRNA expression were quantified by semi
      quantitative PCR. RESULTS: Compared to the mice treated with HDMTX, CF, and
      amifostine, mice treated with Amifostine-CF group were heavier and had greater
      villus height, crypt depth, and normal white blood cell count and lower diarrhea
      rate and mortality than the HDMTX, CF and amifostine groups. There was a
      significant decrease in enterocyte apoptosis in amifostine-CF mice compared with
      the HDMTX and CF groups. CONCLUSIONS: The effect of amifostine plus CF was
      greater than amifostine or CF alone in preventing high-dose methotrexate-induced
      intestinal mucositis and improving intestinal recovery in mice.

PMID- 23979432
TI  - Revenge of the phages: defeating bacterial defences.
AB  - Bacteria and their viral predators (bacteriophages) are locked in a constant
      battle. In order to proliferate in phage-rich environments, bacteria have an
      impressive arsenal of defence mechanisms, and in response, phages have evolved
      counter-strategies to evade these antiviral systems. In this Review, we describe
      the various tactics that are used by phages to overcome bacterial resistance
      mechanisms, including adsorption inhibition, restriction-modification, CRISPR-Cas
      (clustered regularly interspaced short palindromic repeats-CRISPR-associated
      proteins) systems and abortive infection. Furthermore, we consider how these
      observations have enhanced our knowledge of phage biology, evolution and phage
      host interactions. 

PMID- 23979436
TI  - Toll-like receptors mediated signalings: friends or enemies?

PMID- 23979435
TI  - Severe disease activity and cytomegalovirus colitis are predictive of a
      nonresponse to infliximab in patients with ulcerative colitis.
AB  - BACKGROUND AND AIMS: The role of infliximab in the treatment of patients with
      ulcerative colitis (UC) in Asia is still unclear. The aim of this study was to
      evaluate the clinical outcomes of infliximab therapy in Korean UC patients,
      including efficacy and predictors of response. METHODS: Patients who received
      infliximab induction therapy for moderate to severe UC at Asan Medical Center
      were retrospectively analyzed. The demographic characteristics of these patients
      and their clinical outcomes following infliximab therapy were evaluated. RESULTS:
      Of the 89 UC patients receiving infliximab induction therapy, 53 (59.6%) were
      steroid-refractory and 36 (40.4%) were steroid-dependent. At the initiation of
      infliximab, the median Mayo score was 9 (range 7-12). After the induction therapy
      of infliximab, 59 patients (66.3%) demonstrated a clinical response at week 8, of
      which 29 (32.6%) were determined to be in clinical remission. A colectomy was
      performed within 1 year after infliximab initiation in 11 (36.7%) of 30 patients
      who displayed no clinical response to infliximab therapy, but in none of the 59
      patients who showed a response to this drug (p<0.001). Multivariate regression
      analysis identified severe disease (Mayo score>=11) at the initiation of
      infliximab (p=0.007) and history of cytomegalovirus colitis within 3 months prior
      to infliximab treatment (p=0.001) as independent positive predictors of
      nonresponse to infliximab. CONCLUSIONS: The efficacy of infliximab in Korean UC
      patients seems to be similar to that of previously published Western reports.
      Severe disease and a history of cytomegalovirus colitis are predictors of a
      nonresponse to infliximab.

PMID- 23979438
TI  - An elusive cause of severe gastrointestinal bleeding.

PMID- 23979437
TI  - The correlation between the subsets of tumor infiltrating memory T cells and the
      expression of indoleamine 2,3-dioxygenase in gastric cancer.
AB  - BACKGROUNDS: Although many researchers have concentrated on the mechanism of T
      cell anergy resulting from over-expression of Indoleamine 2,3-dioxygenase (IDO),
      it remains unclear what alterations will developed in memory T cells (Tm) under
      over-expression of IDO. METHODS: Immunohistochemical staining for IDO expression
      in gastric cancer tissues (n=50) was carried out. Tumor-infiltrating memory Tm
      cells were counted by flow cytometry. The association between IDO expression and
      the subsets of tumor infiltrating Tm are discussed. RESULTS: The higher IDO
      expressions were significantly associated with deeper invasion (P=0.016) and
      higher frequencies (P=0.038) of lymph node metastasis. The lower tumor
      infiltrating CD4+Tm were significantly associated with the advanced clinical
      stage (P=0.026) and lymph node metastasis (P=0.016). The lower percentages of
      CD8+Tm were significantly related to undifferentiated histological type (P=0.042)
      and lymph node metastasis (P=0.037). However, the lower percentage of CD8+Tem was
      significantly correlated to differentiated histological type (P=0.017), lower
      frequencies of lymph node metastasis (P=0.014), and earlier clinical stage
      (P=0.008). The higher IDO expression patients had significantly lower percentages
      of CD4+Tm (P=0.012) and CD8+Tm (P=0.033). Nevertheless, it was confirmed that the
      higher level of IDO expression correlated with higher percentages of CD8+Tm cells
      in univariate and multivariate analysis (P=0.011). CONCLUSION: IDO over
      expression and Tm in tumor microenvironments were correlated with the disease
      stage and histological type of gastric cancer. Higher IDO expression was related
      to the lower percentage of CD4+Tm and CD8+Tm, whereas the higher level of IDO
      expression related with a higher percentage of CD8+Tem.

PMID- 23979439
TI  - Risks for celiac disease: bacteria make it three.

PMID- 23979440
TI  - Energy, oxidative stress, and inflammation in the colon.

PMID- 23979441
TI  - Hypoxia-induced snail expression through transcriptional regulation by HIF-1alpha
      in pancreatic cancer cells.
AB  - BACKGROUND: Intratumoral hypoxia and epithelial-mesenchymal transition are
      involved in tumor invasion and metastasis. AIMS: This study investigated the
      molecular mechanisms that relay the hypoxia signal into the epithelial
      mesenchymal transition and metastasis. METHODS: Morphology analysis and tumor
      cell migration and invasion assays were performed to detect phenotypic changes of
      pancreatic cancer cells under normoxic and hypoxic conditions after lentiviral
      HIF-1alpha shRNA transfection. Quantitative reverse transcription polymerase
      chain reaction, western blot, and immunohistochemistry were used to detect gene
      expression in pancreatic cancer cell lines and tissues or normal pancreatic
      tissues. Luciferase, gel shift, and ChIP assays were used to assess gene
      regulation. RESULTS: Under hypoxic conditions, these tumor cells underwent
      typical morphological and molecular changes to epithelial-mesenchymal transition.
      Moreover, Snail expression was induced by hypoxic conditions and was regulated by
      HIF-1alpha expression at the transcriptional level through HIF-1alpha-binding to
      the second site of hypoxia-responsive elements of the Snail gene promoter. In
      addition, Snail expression was associated with HIF-1alpha expression in
      pancreatic cancer tissues, and expression of both was associated with tumor
      metastasis and poor patient survival. CONCLUSIONS: Our study provides key
      evidence that HIF-1alpha and Snail are responsible for hypoxia-induced metastasis
      phenotypes in pancreatic cancer and that HIF-1alpha and Snail expression can be
      used as biomarkers to predict tumor metastasis and patient survival.

PMID- 23979443
TI  - [The buried penis : Indications, a new technique and the results].
AB  - The buried penis describes a bunch etiologies and clinical presentations of which
      the congenital form is rare. In the past different techniques had been described,
      using inner prepuce after mobilization to cover the penile shaft. This can lead
      to persistent edema of the skin. We developed a new technique to reduce the rate
      of postoperative edema.

PMID- 23979442
TI  - Endoscopic papillary large balloon dilation as a salvage procedure for basket
      impaction during retrieval of common bile duct stones.

PMID- 23979444
TI  - [Statement on Porzsolt in "monitor healthcare research"].

PMID- 23979445
TI  - [Invasion patterns and metastasis of urothelial carcinoma. A challenge for
      translational research].
AB  - Local invasion of cancer cells occurs early during the progression of urothelial
      carcinoma. Micrometastatic disease and the presence of nodal metastases are major
      causes of cancer-specific mortality following radical surgery. Only surrogate
      markers for aggressive and micrometastatic disease have been identified. The
      metastatic cascade is complex, including multiple steps from initial invasion to
      colonization and proliferation at distant sites. The initial mechanisms of cancer
      cell dissemination in urothelial carcinoma are poorly understood. Various
      proteases, chemokines and growth factors are involved in this process and
      alterations of the lymphatic system may promote systemic spread. There is a high
      demand for therapeutic targeting of the metastatic process. Functional
      preclinical studies in representative models are therefore required to better
      elucidate the multiple steps of progression. We review the current knowledge on
      factors associated with metastasis in urothelial carcinoma. Preclinical
      approaches to identify key player molecules for invasion and to develop new
      therapeutic strategies are discussed.

PMID- 23979446
TI  - [Clinical stage I seminoma. Is surveillance a new therapy standard?].
AB  - BACKGROUND: The therapy of stage I seminoma is under constant change. While
      surveillance, adjuvant radiotherapy and adjuvant chemotherapy were seen as equal
      therapeutic alternatives up to a few years ago, recently published studies make
      it necessary to adopt a more differentiated approach. DISCUSSION: In this review,
      recent data on the long-term effects of adjuvant radiotherapy and chemotherapy,
      the question of risk stratification as well as the advantages and limitations of
      a surveillance strategy are discussed.

PMID- 23979447
TI  - Late divergence of survival curves in cancer immunotherapy trials: interpretation
      and implications.
AB  - Late divergence of survival curves of treated patients and controls is commonly
      seen in successful cancer immunotherapy trials. Although late survival curve
      divergence may be caused by a delayed action of therapy, it may also be related
      to early effects of the treatment. We suggest that late survival divergence most
      often reflects a specific benefit of therapy for patients who suffer from a
      comparatively slow progression of disease. The occurrence of delayed survival
      curve divergence has important implications for the statistical analysis of
      immunotherapy trials. Thus, it leads to non-proportional hazard ratios that make
      commonly used statistical tests, e.g., the logrank test, suboptimal. It is
      therefore suggested that the statistical analysis of immunotherapy trials
      primarily should be based on a test that compares the survival curves at or after
      a prespecified, fixed, late time point. 

PMID- 23979448
TI  - Legal threat to infant male circumcision.

PMID- 23979449
TI  - Left hemispheric dominance of vestibular processing indicates lateralization of
      cortical functions in rats.
AB  - Lateralization of cortical functions such as speech dominance, handedness and
      processing of vestibular information are present not only in humans but also in
      ontogenetic older species, e.g. rats. In human functional imaging studies, the
      processing of vestibular information was found to be correlated with the
      hemispherical dominance as determined by the handedness. It is located mainly
      within the right hemisphere in right handers and within the left hemisphere in
      left handers. Since dominance of vestibular processing is unknown in animals, our
      aim was to study the lateralization of cortical processing in a functional
      imaging study applying small-animal positron emission tomography (microPET) and
      galvanic vestibular stimulation in an in vivo rat model. The cortical and
      subcortical network processing vestibular information could be demonstrated and
      correlated with data from other animal studies. By calculating a lateralization
      index as well as flipped region of interest analyses, we found that the
      vestibular processing in rats follows a strong left hemispheric dominance
      independent from the "handedness" of the animals. These findings support the idea
      of an early hemispheric specialization of vestibular cortical functions in
      ontogenetic older species. 

PMID- 23979451
TI  - Evolution of brain complexity and animal minds. Preface.

PMID- 23979450
TI  - Cushing's disease, pseudo-Cushing states and the dexamethasone test: a historical
      and critical review.
AB  - The dexamethasone (DXM) test has been widely used for diagnosing Cushing's
      disease (CD). The purpose of this paper is to review its diagnostic merit based
      on calculation of data extracted from earlier publications. Studies presenting
      individual values for patients with CD and normal subjects were identified
      through PubMed searches and references in pertinent studies. Calculation of the
      retrieved data demonstrated huge variation in the relative suppressibility,
      negative suppression being common. Furthermore, in almost each study retrieved,
      the pre and post DXM values were closely correlated. Finally, the generally
      accepted view that DXM causes less suppression in Cushing's disease than in
      euadrenal controls appears unfounded. A central issue in the definition of so
      called "pseudo-Cushing's states" is failure to suppress cortisol secretion with
      DXM. From analysis of the literature it appears quite possible that this does not
      reflect a specific endocrine deficit, but a physiological "stress" reaction. The
      above issues question the diagnostic value of the test, in particular in
      clinically and biochemically borderline cases. 

PMID- 23979452
TI  - Evolution of complex higher brain centers and behaviors: behavioral correlates of
      mushroom body elaboration in insects.
AB  - Large, complex higher brain centers have evolved many times independently within
      the vertebrates, but the selective pressures driving these acquisitions have been
      difficult to pinpoint. It is well established that sensory brain centers become
      larger and more structurally complex to accommodate processing of a particularly
      important sensory modality. When higher brain centers such as the cerebral cortex
      become greatly expanded in a particular lineage, it is likely to support the
      coordination and execution of more complex behaviors, such as those that require
      flexibility, learning, and social interaction, in response to selective pressures
      that made these new behaviors advantageous. Vertebrate studies have established a
      link between complex behaviors, particularly those associated with sociality, and
      evolutionary expansions of telencephalic higher brain centers. Enlarged higher
      brain centers have convergently evolved in groups such as the insects, in which
      multimodal integration and learning and memory centers called the mushroom bodies
      have become greatly elaborated in at least four independent lineages. Is it
      possible that similar selective pressures acting on equivalent behavioral outputs
      drove the evolution of large higher brain centers in all bilaterians? Sociality
      has greatly impacted brain evolution in vertebrates such as primates, but it has
      not been a major driver of higher brain center enlargement in insects. However,
      feeding behaviors requiring flexibility and learning are associated with large
      higher brain centers in both phyla. Selection for the ability to support
      behavioral flexibility appears to be a common thread underlying the evolution of
      large higher brain centers, but the precise nature of these computations and
      behaviors may vary.

PMID- 23979453
TI  - How nervous systems evolve in relation to their embodiment: what we can learn
      from octopuses and other molluscs.
AB  - Cephalopods such as the octopus show the most advanced behavior among
      invertebrates, which they accomplish with an exceptionally flexible body plan. In
      this review I propose that the embodied organization approach, developed by
      roboticists to design efficient autonomous robots, is useful for understanding
      the evolution and development of the efficient adaptive interaction of animals
      with their environment, using the octopus as the leading example. The embodied
      organization approach explains adaptive behavior as emerging from the continuous
      dynamical and reciprocal physical and informational interactions between four
      elements: the controller, the mechanical and the sensory systems and the
      environment. In contrast to hierarchical organization, in embodied organization,
      self-organization processes can take part in the emergence of the adaptive
      properties. I first discuss how the embodiment concept explains covariation of
      body form, nervous system organization, and level of behavioral complexity using
      the Mollusca as an example. This is an ideal phylum to test such a qualitative
      correlation between body/brain/behavior, because they show the greatest
      variations of body plan within a single phylum. In some cases the covariation of
      nervous system and body structure seems to arise independently of close
      phylogenetic relationships. Next, I dwell on the octopus as an ideal model to
      test the embodiment concept within a single biological system. Here, the unusual
      body morphology of the octopus exposes the uniqueness of the four components
      comprising the octopus' embodiment. Considering together the results from
      behavioral, physiological, anatomical, and motor control research suggests that
      these four elements mutually influence each other. It is this mutual interactions
      and self-organization which have led to their unique evolution and development to
      create the unique and highly efficient octopus embodiment.

PMID- 23979454
TI  - The pallium and mind/behavior relationships in teleost fishes.
AB  - Three interrelated pallial areas mediate behaviors reflective of the cognitive
      and emotional aspects of the teleost mind. The dorsocentral area (Dc) has
      specific associations with both of the other pallial areas and projects to major
      lower sensorimotor centers. While Dc generally functions as an output or
      modulatory component of the pallium, it probably also has integrative features
      important for certain behaviors. The dorsolateral region (Dl) has dorsal (Dld)
      and ventral (Dlv) divisions. In association with the dorsal part of Dc, Dld
      processes visual information via a 'tectal loop' which is hypertrophied in
      certain coral reef species. The region also receives afferents related to other
      modalities. Functionally, Dld resembles the tetrapod sensory neocortex.
      Anatomical and behavioral data (i.e. involvement in spatial and temporal
      learning) strongly suggest that Dlv is homologous to the tetrapod hippocampus.
      The dorsal part of the dorsomedial area (Dmd) processes acoustic, lateral line,
      gustatory, and multimodal information. It has reciprocal connections with Dld
      such that the Dmd and Dld together can be considered the teleost nonolfactory
      'sensory pallium'. Behavioral studies indicate that Dmd creates the 'fear'
      necessary for defense/escape and avoidance behaviors and controls several
      components of species-typical sexual and aggressive behavior (responsiveness,
      behavioral sequencing, and aspects of social cognition). While the functional
      results generally support the anatomical evidence that Dmd is homologous to the
      tetrapod amygdala, a case can also be made that Dmd has 'sensory neocortex-like'
      features. Understanding the interrelationships of Dl, Dmd, and Dc seems a
      necessary 'next step' in the identification of the neural processes responsible
      for mental experiences such as those of a unified sensory experience (Umwelt) or
      of feelings of discomfort versus well-being.

PMID- 23979455
TI  - Variation in reptilian brains and cognition.
AB  - The class Reptilia is monophyletic, if all synapsid tetrapods are excluded and
      birds are included. The phylogenetic position of turtles within the reptilian
      clade is still problematic, but recent microRNA data suggest that turtles are the
      sister group to lepidosaurians. Brain-body data for approximately 60 reptilian
      taxa indicate that the relative brain size for a given body weight varies some
      six-fold among reptiles, with some turtles and lizards having relatively large
      brains and other turtles and lizards having relatively small brains. Snakes
      appear to be characterized by relatively small brains, and crocodilians appear to
      possess the largest brains among living reptiles, with the exception of birds.
      Data on the relative size of major brain divisions among tetrapods are limited,
      but the telencephalic and cerebellar hemispheres account for much of the
      variation. Telencephalic hemispheres in reptiles are approximately twice as large
      as those in amphibians, and the relative size of the telencephalic hemispheres in
      monitor lizards and crocodilians approaches that in basal birds and mammals. New
      data on the relative volumes of telencephalic pallial divisions in tetrapods
      reveal that the dorsal ventricular ridge, a ventral pallial derivative, accounts
      for much of the increase in pallial size that characterizes reptiles. Studies of
      spatial and visual cognition in nonavian reptiles reveal that they learn mazes
      and make visual discriminations as rapidly as most birds and mammals. Studies of
      social cognition and novel behavior, including play, reveal levels of complexity
      not previously believed to exist among nonavian reptiles. Given this level of
      neural and cognitive complexity, it is possible that consciousness has evolved
      numerous times, independently, among reptiles.

PMID- 23979456
TI  - Bird brains and tool use: beyond instrumental conditioning.
AB  - Few displays of complex cognition are as intriguing as nonhuman tool use. Long
      thought to be unique to humans, evidence for tool use and manufacture has now
      been gathered in chimpanzees, dolphins, and elephants. Outside of mammals, tool
      use is most common in birds, especially in corvids and parrots. The present paper
      reviews the evidence for avian tool use, both in the wild and in laboratory
      settings. It also places this behavioral evidence in the context of longstanding
      debates about the kinds of mental processes nonhumans can perform. Descartes
      argued that animals are unable to think because they are soulless machines,
      incapable of flexible behavior. Later, as human machines became more
      sophisticated and psychologists discovered classical and instrumental
      conditioning, skepticism about animal thinking decreased. However, behaviors that
      involve more than simple conditioning continued to elicit skepticism, especially
      among behaviorists. Nonetheless, as reviewed here, strong behavioral data now
      indicate that tool use in some birds cannot be explained as resulting entirely
      from instrumental conditioning. The neural substrates of tool use in birds remain
      unclear, but the available data point mainly to the caudolateral nidopallium,
      which shares both functional and structural features with the mammalian
      prefrontal cortex. As more data on the neural mechanisms of complex cognition in
      birds accrue, skepticism about those mental capacities should continue to wane.

PMID- 23979457
TI  - The evolutions of large brain size in mammals: the 'over-700-gram club quartet'.
AB  - The current paper details our developing understanding of the evolution of large
      brains in mammals. In order to do this, we first define brains that we consider
      to be large--those that have passed the apparent 700-gram ceiling on brain mass
      evolution in the class Mammalia. The over-700-gram club includes certain species
      within the genus Homo, order Cetacea, order Proboscidea, and suborder Pinnipedia.
      Our analysis suggests that selection for body size appears to be the most
      important factor in the evolution of large brain size, but there also appear to
      be internal morphophysiological constraints on large brain size evolution that
      need to be overcome in order for brains to break the 700-gram barrier. These two
      aspects appear to be common themes in the evolution of large brains. This
      significantly diminishes the explanatory value of selection for greater cognitive
      capacities as a principal factor in the evolution of enlarged brain sizes above
      the 700-gram threshold.

PMID- 23979458
TI  - Quinone/hydroquinone-functionalized biointerfaces for biological applications
      from the macro- to nano-scale.
AB  - Quinones/hydroquinones (Q/HQ) are a class of prototypical redox molecules that
      play a variety of vital roles in biology, particularly in electron transfer and
      energy conservation systems. Biointerfaces supported on solid substrates or
      nanomaterials are widely used as biomimetic platforms that connect biological
      materials with artificial interfaces. Q/HQ-functionalized biointerfaces provide a
      new means for understanding the complex behaviors of Q/HQ at the interfaces of
      biological systems, and for further development of novel biomaterials and
      biosensors. This tutorial review provides a brief introduction to the recent
      advances in this field. We begin with the current methods used to functionalize
      Q/HQ on biointerfaces from the macro- to nano-scale (both solid substrates and
      nanomaterials), and then discuss their wide biological applications. Particularly
      exciting applications arise when Q/HQ-functionalized biointerface systems are
      coupled with biomimetic strategies. These systems can be used as models of other
      functionalized biointerfaces for biological applications, providing new insights
      into the future development of this area. 

PMID- 23979459
TI  - Microfluidic generation of magnetoresponsive Janus photonic crystal particles.
AB  - Janus particles with features of an anisotropic photonic band gap (PBG) structure
      and magnetic property have been achieved by phase separation and self-assembly of
      nanoparticles in microfluidic droplets. The resultant particles enable optical
      encoding and magnetically controllable motion, making them excellent functional
      encoded particles in biomedical applications. 

PMID- 23979460
TI  - Hybrid photomultiplier tube and photodiode parallel detection array for wideband
      optical spectroscopy of the breast guided by magnetic resonance imaging.
AB  - A new optical parallel detection system of hybrid frequency and continuous-wave
      domains was developed to improve the data quality and accuracy in recovery of all
      breast optical properties. This new system was deployed in a previously existing
      system for magnetic resonance imaging (MRI)-guided spectroscopy, and allows
      incorporation of additional near-infrared wavelengths beyond 850 nm, with
      interlaced channels of photomultiplier tubes (PMTs) and silicon photodiodes
      (PDs). The acquisition time for obtaining frequency-domain data at six
      wavelengths (660, 735, 785, 808, 826, and 849 nm) and continuous-wave data at
      three wavelengths (903, 912, and 948 nm) is 12 min. The dynamic ranges of the
      detected signal are 105 and 106 for PMT and PD detectors, respectively. Compared
      to the previous detection system, the SNR ratio of frequency-domain detection was
      improved by nearly 103 through the addition of an RF amplifier and the
      utilization of programmable gain. The current system is being utilized in a
      clinical trial imaging suspected breast cancer tumors as detected by contrast MRI
      scans.

PMID- 23979461
TI  - Lipid droplet pattern and nondroplet-like structure in two fat mutants of
      Caenorhabditis elegans revealed by coherent anti-Stokes Raman scattering
      microscopy.
AB  - Lipid is an important energy source and essential component for plasma and
      organelle membranes in all kinds of cells. Coherent anti-Stokes Raman scattering
      (CARS) microscopy is a label-free and nonlinear optical technique that can be
      used to monitor the lipid distribution in live organisms. Here, we utilize CARS
      microscopy to investigate the pattern of lipid droplets in two live
      Caenorhabditis elegans mutants (fat-2 and fat-3). The CARS images showed a
      striking decrease in the size, number, and content of lipid droplets in the fat-2
      mutant but a slight difference in the fat-3 mutant as compared with the wild-type
      worm. Moreover, a nondroplet-like structure with enhanced CARS signal was
      detected for the first time in the uterus of fat-2 and fat-3 mutants. In
      addition, transgenic fat-2 mutant expressing a GFP fusion protein of vitellogenin
      2 (a yolk lipoprotein) revealed that the enhanced CARS signal colocalized with
      the GFP signal, which suggests that the nondroplet-like structure is primarily
      due to the accumulation of yolk lipoproteins. Together, this study implies that
      CARS microscopy is a potential tool to study the distribution of yolk
      lipoproteins, in addition to lipid droplets, in live animals.

PMID- 23979462
TI  - The cost of quality in pharmacy.

PMID- 23979463
TI  - Comparison of endotoxin testing methods for pharmaceutical products.

PMID- 23979464
TI  - Phenytoin injections: from compounding to cerebyx.

PMID- 23979465
TI  - Sterile compounding of respiratory inhalation solutions.

PMID- 23979466
TI  - Pediatric dermatitis.

PMID- 23979468
TI  - Regulatory and operational issues of founding a compounding pharmacy.

PMID- 23979467
TI  - Establishing and standardizing preferred pharmacy practices in a multioffice
      infusion company, part 1.

PMID- 23979469
TI  - Medications discontinued in the United States.

PMID- 23979470
TI  - Basics of compounding: clinical studies.

PMID- 23979471
TI  - Andropause: a review of treatment options.

PMID- 23979472
TI  - Chemical stability of furosemide in minibags and polypropylene syringes.
AB  - Furosemide is a loop diuretic that has been administered intravenously for years;
      however, its chemical stability has been determined only at dilute
      concentrations. The stability of furosemide diluted with 0.9% sodium chloride
      injection, and stored at either 22 deg C or 6 deg C in minibags (60, 120, and
      160mg/50mL) and polypropylene stringes (10, 20, 40, and 80mg/10mL) and protected
      from light was studied. Samples were collected in triplicate on days 0, 3, 7, 14,
      28, 56, and 84 and then after exposure to fluorescent light for an additional 7
      days at 22 deg C. All samples were analyzed in duplicate by means of a stability
      indicating high-pressure liquid chromatographic assay. Samples were also
      monitored for color, clarity, and changes in pH. All samples remained clear and
      colorless during the study period. The pH of the solutions did not change
      significantly during the study. All analyzed samples were stable for 84 days at
      22 deg C or 6 deg C when protected from light and for an additional 7 days at 22
      deg C when exposed to fluorescent light. 

PMID- 23979473
TI  - pH Stability of Injectable Fentanyl, Bupivacaine, or Clonidine Solution or a
      Ternary Mixture in 0.9% Sodium Chloride in Two Types of Polypropylene Syringes.
AB  - The pH stability of injectable fentanyl, bupivacaine, or clonidine solution or a
      ternary mixture in 0.9% sodium chloride, all of which were stored in
      polypropylene syringes, was determined. Two different types of polypropylene
      syringes were tested: one (Omnifix, B. Braun, Melsungen, Germany) had a synthetic
      latex-free polyisoprene piston and the other (Terumo, Leuven, Belgium) did not
      contain natural rubber or synthetic rubber. Forty-eight Omnifix 50-mL syringes
      and 120 Terumo 20-mL syringes were tested. The syringes were filled with a
      fentanyl citrate solution 35 microgram/mL (stored in 12 Omnifix and 30 Terumo
      syringes), a bupivacaine hydrochloride solution 1mg/mL (12 Omnifix and 30 Terumo
      syringes), a clonidine hydrochloride solution 9 micrograms/mL (12 Omnifix and 30
      Terumo syringes), or a ternary mixture in 0.9% sodium chloride (12 Omnifix and 30
      Terumo syringes). The syringes were stored for 30 days at 4 deg C, 21 deg C, and
      35 deg C. Duplicate samples were prepared, observed for precipitation and color
      change, and measured for pH immediately after preparation and at 1, 2, 5, 7, 9,
      12, 16, 23, and 30 days of storage. There was no color change or precipitation in
      any sample during 30 days of storage at any of the temperatures studied. There
      was no change in the pH of the fentanyl, bupivacaine, or clonidine soltuions or
      in the ternary mixtrue stored in Terumo syringes for 30 days of storage at 4 deg
      C, 21 deg C, and 35 deg C. Omnifix syringes performed differently with different
      drug solutions. No siginicant change in the pH of the fentanyl bupivacaine, or
      clonidine solutions or of the ternary mixture stored in the Omnifix syringes was
      observed during 30 days of storage at 4 deg C, 21 deg C, and 35 deg C, except for
      the clonidine solutions stored at 21 deg C and 35 deg C. 

PMID- 23979474
TI  - Stability of neostigmine methylsulfate injection at ambient temperature and 4 deg
      C in polypropylene syringes.
AB  - The stability of 1.0-mg/mL neostigmine methylsulfate injection in 6-mL
      polypropylene syringes stored at ambient temperature under continuous fluorescent
      light and at 4 deg C for up to 90 days was investigated. Concentration levels of
      neostigmine methylsulfate injection were determined at 0, 1, 4, 7, 15, 30, 45,
      60, and 90 days after preparation of the syringes by means of a high-performance
      liquid chromatographic stability-indicating assay. Phenol, which was present as a
      preservative in the injection, did not interfere with the assay. The injections
      in plastic syringes were stable for up to 90 days at both ambient temperature and
      at 4 deg C. The pH of neostigmine methylsulfate injection did not change
      appreciable over the 90-day study period. These data support the stability of
      neostigmine methylsulfate injection under the storage conditions investigated in
      this study. 

PMID- 23979475
TI  - Age and gender effects on the proximal propagation of an impulsive force along
      the adult human upper extremity.
AB  - We tested the null hypotheses that neither age, gender nor muscle pre
      cocontraction state affect the latencies of changes in upper extremity kinematics
      or elbow muscle activity following an impulsive force to the hand. Thirty-eight
      healthy young and older adult volunteers lay prone on an apparatus with shoulders
      flexed 75 degrees  and arms slightly flexed. The non-dominant hand was subjected
      to three trials of impulsive loading with arm muscles precontracted to 25, 50, or
      75% of maximum pre-cocontraction levels. Limb kinematic data and upper extremity
      electromyographic (EMG) activity were acquired. The results showed that pre
      cocontraction muscle level (p < 0.001) and gender (p < 0.05 for wrist and
      shoulder) affected joint displacement onset times and age affected EMG onset
      times (p < 0.05). The peak applied force (F1) occurred a mean (+/- SD) 27 (+/- 2)
      ms after impact. The latencies for the wrist, elbow, and shoulder displacements
      were 21 +/- 3, 29 +/- 5, and 34 +/- 7 ms, respectively. Because the latencies for
      elbow flexion and lateral triceps EMG were 23 +/- 5 and 84 +/- 8 ms,
      respectively, muscle pre-activation rather than stretch reflexes prevent arm
      buckling under impulsive end loads.

PMID- 23979476
TI  - Longitudinal follow-up of the mental health of unaccompanied refugee minors.
AB  - Despite growing numbers of unaccompanied refugee minors (UMs) in Europe, and
      evidence that this group is at risk of developing mental health problems, there
      still remain important knowledge gaps regarding the development of UMs' mental
      health during their trajectories in the host country and, in particular, the
      possible influencing role of traumatic experiences and daily stressors therein.
      This study therefore followed 103 UMs from the moment they arrived in Belgium
      until 18 months later. Traumatic experiences (SLE), mental health symptoms (HSCL
      37A, RATS) and daily stressors (DSSYR) were measured at arrival in Belgium, after
      6 and 18 months. UMs reported generally high scores on anxiety, depression and
      post-traumatic stress disorder (PTSD). Linear mixed model analysis showed no
      significant differences in mental health scores over time, pointing towards the
      possible long-term persistence of mental health problems in this population. The
      number of traumatic experiences and the number of daily stressors leaded to a
      significant higher symptom level of depression (daily stressors), anxiety and
      PTSD (traumatic experiences and daily stressors). European migration policies
      need to reduce the impact of daily stressors on UMs' mental health by
      ameliorating the reception and care facilities for this group. Moreover, regular
      mental health screenings are needed, in combination with, if needed, adapted
      psychosocial and therapeutic care. 

PMID- 23979477
TI  - Isolation and culture of mouse primary pancreatic acinar cells.
AB  - This protocol permits rapid isolation (in less than 1 hr) of murine pancreatic
      acini, making it possible to maintain them in culture for more than one week.
      More than 20 x 10(6) acinar cells can be obtained from a single murine pancreas.
      This protocol offers the possibility to independently process as many as 10
      pancreases in parallel. Because it preserves acinar architecture, this model is
      well suited for studying the physiology of the exocrine pancreas in vitro in
      contrast to cell lines established from pancreatic tumors, which display many
      genetic alterations resulting in partial or total loss of their acinar
      differentiation.

PMID- 23979478
TI  - A refractive index sensor based on the resonant coupling to cladding modes in a
      fiber loop.
AB  - We report an easy-to-build, compact, and low-cost optical fiber refractive index
      sensor. It consists of a single fiber loop whose transmission spectra exhibit a
      series of notches produced by the resonant coupling between the fundamental mode
      and the cladding modes in a uniformly bent fiber. The wavelength of the notches,
      distributed in a wavelength span from 1,400 to 1,700 nm, can be tuned by
      adjusting the diameter of the fiber loop and are sensitive to refractive index
      changes of the external medium. Sensitivities of 170 and 800 nm per refractive
      index unit for water solutions and for the refractive index interval 1.40-1.442,
      respectively, are demonstrated. We estimate a long range resolution of 3 * 10(-4)
      and a short range resolution of 2 * 10(-5) for water solutions.

PMID- 23979479
TI  - Fetal electrocardiogram (fECG) gated MRI.
AB  - We have developed a Magnetic Resonance Imaging (MRI)-compatible system to enable
      gating of a scanner to the heartbeat of a foetus for cardiac, umbilical cord flow
      and other possible imaging applications. We performed radiofrequency safety
      testing prior to a fetal electrocardiogram (fECG) gated imaging study in pregnant
      volunteers (n = 3). A compact monitoring device with advanced software capable of
      reliably detecting both the maternal electrocardiogram (mECG) and fECG
      simultaneously was modified by the manufacturer (Monica Healthcare, Nottingham,
      UK) to provide an external TTL trigger signal from the detected fECG which could
      be used to trigger a standard 1.5 T MR (GE Healthcare, Milwaukee, WI, USA) gating
      system with suitable attenuation. The MR scanner was tested by triggering rapidly
      during image acquisition at a typical fetal heart rate (123 beats per minute)
      using a simulated fECG waveform fed into the gating system. Gated MR images were
      also acquired from volunteers who were attending for a repeat fetal Central
      Nervous System (CNS) examination using an additional rapid cardiac imaging
      sequence triggered from the measured fECG. No adverse safety effects were
      encountered. This is the first time fECG gating has been used with MRI and opens
      up a range of new possibilities to study a developing foetus. 

PMID- 23979480
TI  - GPS/MEMS INS data fusion and map matching in urban areas.
AB  - This paper presents an evaluation of the map-matching scheme of an integrated
      GPS/INS system in urban areas. Data fusion using a Kalman filter and map matching
      are effective approaches to improve the performance of navigation system
      applications based on GPS/MEMS IMUs. The study considers the curve-to-curve
      matching algorithm after Kalman filtering to correct mismatch and eliminate
      redundancy. By applying data fusion and map matching, the study easily
      accomplished mapping of a GPS/INS trajectory onto the road network. The results
      demonstrate the effectiveness of the algorithms in controlling the INS drift
      error and indicate the potential of low-cost MEMS IMUs in navigation
      applications. 

PMID- 23979481
TI  - Human body parts tracking and kinematic features assessment based on RSSI and
      inertial sensor measurements.
AB  - Acquisition of patient kinematics in different environments plays an important
      role in the detection of risk situations such as fall detection in elderly
      patients, in rehabilitation of patients with injuries, and in the design of
      treatment plans for patients with neurological diseases. Received Signal Strength
      Indicator (RSSI) measurements in a Body Area Network (BAN), capture the signal
      power on a radio link. The main aim of this paper is to demonstrate the potential
      of utilizing RSSI measurements in assessment of human kinematic features, and to
      give methods to determine these features. RSSI measurements can be used for
      tracking different body parts' displacements on scales of a few centimeters, for
      classifying motion and gait patterns instead of inertial sensors, and to serve as
      an additional reference to other sensors, in particular inertial sensors.
      Criteria and analytical methods for body part tracking, kinematic motion feature
      extraction, and a Kalman filter model for aggregation of RSSI and inertial sensor
      were derived. The methods were verified by a set of experiments performed in an
      indoor environment. In the future, the use of RSSI measurements can help in
      continuous assessment of various kinematic features of patients during their
      daily life activities and enhance medical diagnosis accuracy with lower costs. 

PMID- 23979482
TI  - Lightweight filter architecture for energy efficient mobile vehicle localization
      based on a distributed acoustic sensor network.
AB  - The generic properties of an acoustic signal provide numerous benefits for
      localization by applying energy-based methods over a deployed wireless sensor
      network (WSN). However, the signal generated by a stationary target utilizes a
      significant amount of bandwidth and power in the system without providing further
      position information. For vehicle localization, this paper proposes a novel
      proximity velocity vector estimator (PVVE) node architecture in order to capture
      the energy from a moving vehicle and reject the signal from motionless
      automobiles around the WSN node. A cascade structure between analog envelope
      detector and digital exponential smoothing filter presents the velocity vector
      sensitive output with low analog circuit and digital computation complexity. The
      optimal parameters in the exponential smoothing filter are obtained by analytical
      and mathematical methods for maximum variation over the vehicle speed. For
      stationary targets, the derived simulation based on the acoustic field parameters
      demonstrates that the system significantly reduces the communication requirements
      with low complexity and can be expected to extend the operation time
      considerably. 

PMID- 23979483
TI  - Impairment of brain mitochondrial functions by beta-hemolytic Group B
      Streptococcus. Effect of cardiolipin and phosphatidylcholine.
AB  - Group B Streptococcus (GBS) causes severe infection in the central nervous
      system. In this study, brain mitochondrial function was investigated by
      simulating infection of isolated mitochondria with GBS, which resulted in loss of
      mitochondrial activity. The beta-hemolysin expressing strains GBS-III-NEM316 and
      GBS-III-COH31, but not the gGBS-III-COH31 that does not express beta-hemolysin,
      caused dissipation of preformed mitochondrial membrane potential (Deltapsim).
      This indicates that beta-hemolysin is responsible for decreasing of the reducing
      power of mitochondria. GBS-III-COH31 interacted with mitochondria causing
      increase of oxygen consumption, due to uncoupling of respiration, blocking of ATP
      synthesis, and cytochrome c release outside mitochondria. Moreover, the
      mitochondrial systems contributing to the control of cellular Ca(2+) uptake were
      lost. In spite of these alterations, mitochondrial phospholipid content and
      composition did not change significantly, as evaluated by MALDI-TOF mass
      spectrometry. However, exogenous cardiolipin (CL) and
      dipalmitoylphosphatidylcholine (DPPC) attenuated the uncoupling effect of GBS-III
      COH31, although with different mechanisms. CL was effective only when fused to
      the inner mitochondrial membrane, probably reducing the extent of GBS-induced
      proton leakage. DPPC, which is not able to fuse with mitochondrial membranes,
      exerted its effect outside mitochondria, likely by shielding mitochondria against
      GBS beta-hemolysin attack. 

PMID- 23979484
TI  - Family history of diabetes is associated with higher risk for prediabetes: a
      multicentre analysis from the German Center for Diabetes Research.
AB  - AIMS/HYPOTHESIS: Prediabetes is a collective term for different subphenotypes
      (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]) with
      different pathophysiologies. A positive family history for type 2 diabetes (FHD)
      is associated with increased risk for type 2 diabetes. We assumed that it would
      also associate with prediabetes, but wondered whether all subphenotypes are
      related to a positive family history. METHODS: In a study population of 8,106 non
      diabetic individuals of European origin collected from four study centres (normal
      glucose tolerance, NGT n = 5,482, IFG and/or IGT n = 2,624), we analysed whether
      having at least one first degree relative with diabetes is associated with
      prediabetes. The analyses were performed using the same models in each population
      separately. Afterwards, a meta-analysis was performed. RESULTS: FHD was
      significantly associated with the risk for prediabetes (IFG and/or IGT, OR 1.40;
      95% CI 1.27, 1.54). This association remained significant in multivariable
      logistic regression models including sex, age and BMI (OR 1.26; 95% CI 1.14,
      1.40). When different prediabetic outcomes were considered separately, the
      association was found for isolated IFG (OR 1.37; 95% CI 1.20, 1.57), isolated IGT
      (OR 1.25; 95% CI 1.07, 1.46) as well as for the combination IFG+IGT (OR 1.64; 95%
      CI 1.40, 1.93). After stratification on BMI, association between FHD and
      prediabetes was seen only in non-obese individuals (BMI < 30 kg/m(2)).
      CONCLUSIONS/INTERPRETATION: We found that FHD is an important risk factor for
      prediabetes, especially for combined IGT and IFG. Its relevance seems to be more
      evident in the non-obese.

PMID- 23979485
TI  - The novel chemokine receptor, G-protein-coupled receptor 75, is expressed by
      islets and is coupled to stimulation of insulin secretion and improved glucose
      homeostasis.
AB  - AIMS/HYPOTHESIS: Chemokine (C-C motif) ligand 5 (CCL5) acts at C-C chemokine
      receptors (CCRs) to promote immune cell recruitment to sites of inflammation, but
      is also an agonist at G-protein-coupled receptor 75 (GPR75), which has very
      limited homology with CCRs. GPR75 is coupled to Gq to elevate intracellular
      calcium, so we investigated whether islets express this receptor and whether its
      activation by CCL5 increases beta cell calcium levels and insulin secretion.
      METHODS: Islet CCL5 receptor mRNA expression was measured by quantitative RT-PCR
      and GPR75 was detected in islets by western blotting and immunohistochemistry. In
      some experiments GPR75 was downregulated by transient transfection with small
      interfering RNA. Real-time changes in intracellular calcium were determined by
      single-cell microfluorimetry. Dynamic insulin secretion from perifused islets was
      quantified by radioimmunoassay. Glucose homeostasis in lean and obese mice was
      determined by measuring glucose and insulin tolerance, and insulin secretion in
      vivo. RESULTS: Mouse and human islets express GPR75 and its ligand CCL5.
      Exogenous CCL5 reversibly increased intracellular calcium in beta cells via
      GPR75, this phenomenon being dependent on phospholipase C activation and calcium
      influx. CCL5 also stimulated insulin secretion from mouse and human islets in
      vitro, and improved glucose tolerance in lean mice and in a mouse model of
      hyperglycaemia and insulin resistance (ob/ob). The improvement in glucose
      tolerance was associated with enhanced insulin secretion in vivo, without changes
      in insulin sensitivity. CONCLUSIONS/INTERPRETATION: Although CCL5 is implicated
      in the pathogenesis of diabetes through activation of CCRs, it has beneficial
      effects on beta cells through GPR75 activation.

PMID- 23979486
TI  - A mathematical model for scanning and catalysis on single-stranded DNA,
      illustrated with activation-induced deoxycytidine deaminase.
AB  - We formulated a master equation-based mathematical model to analyze random
      scanning and catalysis for enzymes that act on single-stranded DNA (ssDNA)
      substrates. Catalytic efficiencies and intrinsic scanning distances are deduced
      from the distribution of positions and gap lengths between a series of catalytic
      events occurring over time, which are detected as point mutations in a lacZalpha
      based reporter sequence containing enzyme target motifs. Mathematical analysis of
      the model shows how scanning motions become separable from the catalysis when the
      proper statistical properties of the mutation pattern are used to interpret the
      readouts. Two-point correlations between all catalytic events determine intrinsic
      scanning distances, whereas gap statistics between mutations determine their
      catalytic efficiencies. Applying this model to activation-induced deoxycytidine
      deaminase (AID), which catalyzes C->U deaminations processively on ssDNA, we have
      established that deaminations of AGC hot motifs occur at a low rate, ~0.03 s(-1),
      and low efficiency, ~3%. AID performs random bidirectional movements for an
      average distance of 6.2 motifs, at a rate of about 15 nucleotides per second, and
      "dwells" at a motif site for 2.7 s while bound >4 min to the same DNA molecule.
      These results provide new and important insights on how AID may be optimized for
      generating mutational diversity in Ig genes, and we discuss how the properties of
      AID acting freely on a "naked" ssDNA relate to the constrained action of AID
      during transcription-dependent somatic hypermutation and class-switch
      recombination. 

PMID- 23979487
TI  - Effects of plant genotype and nitrogen level on bacterial communities in rice
      shoots and roots.
AB  - To examine whether microbial community structure differs across rice genotypes,
      automated ribosomal intergenic spacer analysis (ARISA) was conducted. Nine
      cultivars of Oryza sativa ssp. indica or japonica and seven lines of other Oryza
      species were grown in paddy fields with low, standard, and high levels of N
      fertilization. Multidimensional scaling plots of bacterial ARISA for aerial parts
      of rice (shoots) revealed that the structure of shoot bacterial communities was
      significantly affected by plant genotype (indica or japonica) based on similarity
      tests, whereas root microbiomes were largely affected by the N fertilization
      level. 

PMID- 23979489
TI  - Transplantation: Negative vaccination to modulate transplant immunity.

PMID- 23979490
TI  - Directing resources to where they are the most needed.

PMID- 23979491
TI  - Effects in the upper face of far east Asians after Oriental blepharoplasty: a
      scientific perspective on why Oriental blepharoplasty is essential.
AB  - BACKGROUND: Oriental blepharoplasty is the most frequently performed aesthetic
      surgery among far east Asians (i.e., Korean, Chinese, Japanese, and Taiwanese).
      Numerous studies on oriental blepharoplasty have been published, but only a few,
      if any, have reported on the measurable effects of such surgeries on the upper
      face. To scientifically evaluate the changes in the upper face of young Korean
      adults after oriental blepharoplasty, a periocular morphometry study was
      conducted. METHODS: A retrospective image analysis was used to identify the
      changes in the upper face after oriental blepharoplasty. Preoperative and
      postoperative digital facial images of 612 patients (598 women and 14 men) who
      underwent oriental blepharoplasty were examined. The height of the palpebral
      fissure (HPF), the distance between the highest point of the palpebral fissure of
      the upper eyelid and the eyebrow (DEE), and the distance between the eyebrow and
      the hairline (DEH) were measured to analyze the effects of oriental
      blepharoplasty in the upper face. RESULTS: After oriental blepharoplasty, the HPF
      and DEH increased in length by 11.8 and 4.9 %, respectively, and the DEE
      decreased in length by 14.0 %. Patients who originally did not possess double
      eyelids showed greater changes than those who originally did possess such
      eyelids. Such changes were characterized by a significant inverse correlation
      between the DEE and DEH. In addition, when postoperative changes were measured
      before and after 6 months, the palpebral fissure and forehead showed an even
      greater increase. CONCLUSIONS: Oriental blepharoplasty can induce substantial
      changes in the proportions of the upper face. It can not only increase the size
      of the eyes, but also induce changes in eyebrow position resulting in a more
      refreshed appearance.

PMID- 23979492
TI  - Sorafenib plus dacarbazine in solid tumors: a phase I study with dynamic contrast
      enhanced ultrasonography and genomic analysis of sequential tumor biopsy samples.
AB  - PURPOSE: Improved prognostic accuracy for treatment response and a wider
      understanding of drug effects in humans are crucial for enhancing the utility of
      sorafenib and other promising targeted therapies. We developed a strategy of
      global genomic investigation of sequential tumor biopsy samples at baseline and
      21 days post treatment, and applied this approach in a phase I study of sorafenib
      plus dacarbazine in patients with solid tumors. The objective of this study was
      also to validate functional parameters of DCE-US as surrogate markers to predict
      earlier response. EXPERIMENTAL DESIGN: Patients received 21-day cycles of oral
      sorafenib, 400 mg twice daily and dacarbazine, 1,000 mg/m(2) in a 1-h intravenous
      infusion on day 1. Efficacy was assessed using response evaluation criteria in
      solid tumors. Sequential biopsy samples (baseline and day 21) were obtained from
      the same tumor. Changes from baseline in global gene expression (GE) measured by
      genomic microarrays and in tumor vascularity at baseline, D8, D21, D 42 and every
      2 cycles using dynamic contrast-enhanced ultrasonography (DCE-US) were analyzed
      for patients with and without a clinical response to treatment at 3 months.
      RESULTS: Among 23 patients evaluable for treatment efficacy, 17 were eligible for
      gene expression and DCE-US analyses. One patient achieved a partial response; 14
      exhibited stable disease. Ten patients were defined as exhibiting stable disease
      (SD) and 7, progressive disease (PD) at 3 months. Genomic analyses identified a
      237-gene signature that distinguished SD from PD at 3 months. Of note, CDK4
      overexpression and PDGFR downregulation were associated with PD. Functional
      parameters of DCE-US representing the blood volume at baseline, day 8, and day 21
      were correlated with disease progression at 3 months. CONCLUSIONS: This novel
      approach of sequential investigations in a phase I trial was feasible, detecting
      early changes in gene expression and tumor vascularity evaluated using DCE-US
      that may be predictive of clinical outcome.

PMID- 23979488
TI  - Pathophysiology and treatment of systemic amyloidosis.
AB  - Amyloid is an abnormal extracellular fibrillar protein deposit in the tissues. In
      humans, more than 25 different proteins can adopt a fibrillar conformation in
      vivo that results in the pathognomonic tinctorial property of amyloid (that is,
      green birefringence when an affected tissue specimen is stained with Congo red
      dye and viewed by microscopy under cross-polarized light). Amyloid deposition is
      associated with disturbance of organ function and causes a wide variety of
      clinical syndromes that are classified according to the respective fibril protein
      precursor. Systemic amyloidosis, in which amyloid deposits are widespread and
      typically accumulate gradually, continues to be fatal and is responsible for
      about one in 1,500 deaths per year in the UK. Advances in our understanding of
      the pathogenesis of systemic amyloidosis have resulted in the identification of
      new therapeutic targets, and several drugs with novel mechanisms of action are
      currently under development. Meanwhile, an increased awareness of amyloidosis
      coupled with enhancements to existing diagnostic techniques and therapeutic
      strategies have already resulted in better outcomes for patients with the
      disease. 

PMID- 23979494
TI  - Evaluation of an I-box wind tunnel model for assessment of behavioral responses
      of blow flies.
AB  - The behavioral response of flies to olfactory cues remains the focus of many
      investigations, and wind tunnels have sometimes been employed for assessment of
      this variable in the laboratory. In this study, our aim was to design, construct,
      and operate a new model of I-box wind tunnel with improved efficacy, highlighting
      the use of a new wind tunnel model to investigate the behavioral response of the
      medically important blow fly, Chrysomya megacephala (Fabricius). The I-box dual
      choice wind tunnel designed for this study consists of seven conjoined
      compartments that resulted in a linear apparatus with clear glass tunnel of 30 *
      30 * 190 cm ended both sides with wooden "fan compartments" which are equipped
      with adjustable fans as wind source. The clear glass tunnel consisted of two
      "stimulus compartments" with either presence or absence (control) of bait; two
      "trap compartments" where flies were attracted and allowed to reside; and one
      central "release compartment" where flies were introduced. Wind tunnel
      experiments were carried out in a temperature-controlled room, with a room light
      as a light source and a room-ventilated fan as odor-remover from tunnel out.
      Evaluation of testing parameters revealed that the highest attractive index was
      achieved with the use of 300 g of 1-day tainted pork scrap (pork meat mixed with
      offal) as bait in wind tunnel settings wind speed of 0.58 m/s, during 1.00-5.00
      PM with light intensity of 341.33 lux from vertical light and 135.93 lux from
      horizontal light for testing a group of 60 flies. In addition, no significant
      response of well-fed and 24 h staved flies to this bait under these conditions
      was found. Results of this study supported this new wind tunnel model as a
      suitable apparatus for investigation of behavioral response of blow flies to bait
      chemical cues in the laboratory.

PMID- 23979495
TI  - Bioactive compounds and sensory quality of black and white mulberries grown in
      Spain.
AB  - The objective of this study was to evaluate and compare, for the first time,
      white and black mulberry species in terms of main phytochemical, volatile
      composition and sensory profile characteristics in eight Spanish clones. The
      results showed that black and white mulberry species displayed significant
      different characteristics. PLS analysis has allowed grouping of the clones into
      four groups (i) MA1, MA2 and MN2, (ii) MN3 and MN4, (iii) MA3 and MA4, and (iv)
      MN1. Experimental results proved that Spanish mulberries have potential for fresh
      consumption due to their high antioxidant capacity (10.7-86.1 mg Trolox 100 g(
      1)), polyphenol (76.7-180 mg gallic acid 100 g(-1)) and ellagic acid content (8.7
      15.5 mg 100 g(-1)) as well as considerable amount of volatile compounds (35) with
      desirable attributes, which were scored high by a trained panel. Cultivars from
      the Morus nigra species seem to provide fruits with higher content of bioactive
      compounds and better aptitude for fresh consumption than Morus alba. Differences
      among the species should be attributed to genetics because they were cultivated
      under same conditions. 

PMID- 23979493
TI  - Mefloquine, a new type of compound against schistosomes and other helminthes in
      experimental studies.
AB  - Up to date, schistosomiasis is still prevalent worldwide. It is estimated that
      more than 200 million individuals are infected, and 120 million suffer from
      clinical morbidity. Facing such huge cases of schistosomiasis, only heavy
      reliance on a single praziquantel for schistosomiasis control does not adapt and
      may promote the selection and spread of drug-resistant parasites. Therefore, it
      is an urgent need to develop the new antischistosomal drug. In 2008-2009, the
      antimalarial drug mefloquine, an arylaminoalcohol compound, has been found to be
      effective against schistosomes. According to the experimental studies, the
      deepest impression on the antischistosomal properties of mefloquine can be
      summarized as following points: (1) single dose of mefloquine possesses potential
      effect against three major species of schistosomes (Schistosoma mansoni,
      Schistosoma haematobium, and Schistosoma japonicum) infecting humans; (2) the
      drug displays similar effects against developing stages of juvenile and adult
      schistosomes, which are superior to that of artemisinins and praziquantel; (3) in
      vitro mefloquine exerts direct killing effect on juvenile and adult schistosomes,
      while in vivo, the efficacy of the drug is independent to host immune response,
      (4) mefloquine causes extensive and severe morphological, histopathological, and
      ultrastructural damage to adult and juvenile schistosomes, particularly, the worm
      tegument, musculature, gut, and vitelline glands of female worms are the key
      sites attacked by the drug; (5) combined treatment with mefloquine and
      praziquantel, or artemisinins shows synergistic effect against schistosome in
      experimental therapy,while in initially clinical trial, mefloquine in combination
      with artesunate also exhibits higher cure rates against schistosomiasis hematobia
      and schistosomiasis mansoni, and (6) several mefloquine-related arylmethanols
      exhibit potential effect against schistosomes in vivo, which is a useful clue
      helpful for development of new antischistosomal compound. In the present review,
      we have summarized the major results published in recent years, and the
      significance as well as the prospect for the future study of mefloquine have been
      discussed briefly. 

PMID- 23979496
TI  - Work-related risk factors for incidence of lateral epicondylitis in a large
      working population.
AB  - OBJECTIVES: This study aims to estimate the association between repeated measures
      of occupational risk factors and the incidence of lateral epicondylitis in a
      large working population. METHODS: A total of 3710 workers in a French region
      were included in 2002-2005, and among them 1046 had a complete follow-up in 2007
      2010. At both stages, occupational health physicians assessed the presence of
      lateral epicondylitis and workers self-reported their occupational exposures.
      Poisson models were performed to assess the incidence rate ratios (IRR)
      separately by sex using multiple imputed data. RESULTS: The annual incidence rate
      of lateral epicondylitis was estimated as 1.0 [95% confidence interval (95% CI)
      0.7-1.3] per 100 workers among men and 0.9 (95% CI 0.6-1.3) among women. Workers
      aged >45 years had higher incidence than those aged <30 years (significant at
      10%). Among men, high physical exertion combined with elbow flexion/extension or
      extreme wrist bending (>2 hours/day) was a risk factor, with an age-adjusted IRR
      of 3.2 (95% CI 1.5-6.4) for workers exposed at both questionnaires [3.3 (95% CI
      1.4-7.6) among women]. CONCLUSIONS: This study highlights the importance of
      temporal dimensions for occupational risk factors on the incidence of lateral
      epicondylitis. Further research should evaluate the risk associated with the
      duration and repetition of occupational exposure on the incidence of lateral
      epicondylitis.

PMID- 23979497
TI  - The impact of alcohol use on HIV/STI intervention efficacy in predicting sexually
      transmitted infections among young African-American women.
AB  - The impact of alcohol use on the efficacy of an HIV/STI intervention designed for
      young African-American women in predicting STIs was examined. Eight hundred forty
      eight African-American women, 18-29 years, were randomly assigned to either the
      HIV/STI intervention or a control condition. Participants were assessed on
      alcohol use and provided two vaginal swab specimens for STI testing. Women in the
      intervention who consumed alcohol were less likely to test STI-positive than
      women in the control and abstainers (AOR = 2.47, 95 % CI = 1.01-6.22). STI risk
      factors may vary across different populations. Further research on heavy drinking
      and HIV intervention efficacy is needed. 

PMID- 23979498
TI  - Problematic alcohol use among individuals with HIV: relations with everyday
      memory functioning and HIV symptom severity.
AB  - Problematic alcohol use has been shown to negatively impact cognitive functions
      germane to achieving optimal HIV health outcomes. The present study, a secondary
      data analysis, examined the impact of problematic alcohol use on aspects of
      everyday memory functioning in a sample of 172 HIV-infected individuals (22 %
      female; Mage = 48.37 years, SD = 8.64; 39 % Black/non-Hispanic). Additionally, we
      tested whether self-reported memory functioning explained the relation between
      problematic alcohol use and HIV symptom severity. Results indicated that
      problematic patterns of alcohol use were associated with lower total memory
      functioning, retrieval (e.g., recall-difficulty) and memory for activity (e.g.,
      what you did yesterday) and greater HIV symptom severity. Memory functioning
      mediated the relation between problematic alcohol use and HIV symptom severity.
      However, the direction of this relation was unclear as HIV symptom severity also
      mediated the relation between problematic alcohol use and memory functioning.
      Findings highlight the importance of integrated care for HIV and alcohol use
      disorders and suggest that routine alcohol and cognitive screenings may bolster
      health outcomes among this vulnerable population.

PMID- 23979499
TI  - Super Bowl outcome's association with cardiovascular death.
AB  - BACKGROUND: A previous analysis from Los Angeles showed that death rates
      increased among hometown fans after losing the Super Bowl in 1980 and decreased
      after a win in 1984. Data are unavailable in the era of drug-eluting stents, dual
      antiplatelet therapy, statins, and modern medical therapy. METHODS: Two high
      drama and intense Super Bowls were analyzed: NYC beat New England (Massachusetts)
      in 2008 and Pittsburgh defeated Arizona in 2009. Daily death certificate data
      were obtained. The case period included eight consecutive days beginning Super
      Bowl day. The control period included eight consecutive days beginning Super Bowl
      day in non-case period Super Bowls from 2005 to 2009. RESULTS: After
      Massachusetts' defeat, circulatory deaths increased by 20 % (p = 0.0004) and
      ischemic heart disease deaths increased by 24 % (p = 0.01) in Massachusetts.
      After Pittsburgh's victory circulatory deaths decreased by 25 % (p = 0.046),
      ischemic heart disease deaths decreased by 31 % (p = 0.03), and myocardial
      infarction deaths decreased by 46 % (p = 0.01) in Pittsburgh. Cardiovascular
      death rates did not change in Arizona (all p > 0.19). Massachusetts and
      Pittsburgh show stronger support for their home teams compared with Arizona.
      CONCLUSIONS: A Super Bowl with high drama/intensity can be associated with
      changes in cardiovascular death rates among a fan base with a strong attachment
      to the team even in the contemporary era. An increase in death rates can be
      associated with a loss and a decrease in death rates can be associated with a
      win.

PMID- 23979500
TI  - Compounding for the effects of weapons of mass destruction.
AB  - As incidents of terrorism become more common, pharmacists, and medical
      professionals must plan for a possible domestic terrorist attack involving
      biologic, chemical, or nuclear weapons. For the United States to be truly
      prepared, federal, state, and local agencies must have the knowledge,
      intelligence, training, and supplies to counter this realistic threat of the
      twenty-first century. Terrorists often use chemical, biologic, or limited nuclear
      warfare in which weapons are easier to produce, smaller in size, and have a
      profound psychologic and physical impact. 

PMID- 23979502
TI  - "Natural" or "bioidentical" hormone replacement: what makes the difference? An
      interview with christopher B. Cutter, MD.

PMID- 23979501
TI  - Diabetes mellitus: pathophysiology and complications ?.

PMID- 23979503
TI  - Equine Cushing's Syndrome.

PMID- 23979504
TI  - Establishing and standardizing preferred pharmacy practices in a multioffice
      infusion company, part 2.

PMID- 23979505
TI  - Packaging choices for compounded materials.

PMID- 23979506
TI  - Technology spotlight: barrier isolators.

PMID- 23979507
TI  - Basics of compounding for terrorist attacks, part 1.

PMID- 23979508
TI  - Stability of glycopyrrolate injection at ambient temperature and 4 deg C in
      polypropylene syringes.
AB  - The stability of 0.2-mg/mL glycopyrrolate injection in 6-mL polypropylene
      syringes stored at ambient temperature and at 4 deg C for up to 90 days was
      investigated. A high-performance liquid chromatographic stability-indicating
      assay was used to determine the concentration level of glycopyrrolate injection
      0, 1, 4, 7, 15, 30, 45, 60, and 90 days after preparation of the syringes. Benzyl
      alcohol, which was added as a preservative, did not interfere with the assay. The
      injection in plastic syringes was stable for up to 90 days at both ambient
      temperature and at 4 deg C. The pH of the glycopyrrolate injection did not change
      appreciably during the 90-day study period. These data indicate the stability of
      glycopyrrolate injection under the storage conditions investigated in this study.

PMID- 23979509
TI  - Stability of succinylcholine chloride injection at ambient temperature and 4 deg
      C in polypropylene syringes.
AB  - The stability of 20-mg/mL succinylcholine chloride injection in 12-mL
      polypropylene syringes stored at ambient temperature and 4 deg C for up to 90
      days was investigated. Concentration levels of succinylcholine chloride injection
      were determined at 0, 1, 4, 7, 15, 30, 45, 60, and 90 days after preparation of
      the syringes by means of a high-performance liquid chromatographic stability
      indicating assay. Methylparaben, which was added as a preservative, did not
      interfere with the assay. The loss in potency was less than 10% after 45 days of
      storage at 25 deg C and less than 1% after 90 days of storage at 4 deg C. The pH
      of succinylcholine chloride injection did not change appreciably during the 90
      day study period. 

PMID- 23979510
TI  - Use of Cysteine Hydrochloride Injection To Increase the Solubility of Calcium and
      Phosphates in FreAmine III-Containing Paranteral Nutrition Solutions.
AB  - Numerous factors (including solution pH) that influence the amount of calcium and
      phosphates remaining in solution or precipitating from parenteral nutrition
      solutions have been identified. Increased solubility of calcium and phosphates
      can be achieved in parenteral nutrition formulations by using a suitable acidic
      additive to lower the pH from the natural unadjusted level. The purpose of this
      study was to evaluate the use of cysteine hydrochloride injection as an additive
      to FreAmine III-based parenteral nutrition solutions to increase the solubility
      of calcium and phosphates. In this study, five representative core parenteral
      nutrition formulations containing FreAmine III 1% to 5% were evaluated. Those
      formulations contained cysteine hydrochloride injection 0.5mL (25 mg) per gram of
      amino acids from FreAmine III to lower the pH. Varying amounts of calcium and
      phosphates were added to samples of the core formulations to identify the points
      at which precipitation just began to occur. Five series of concentrations with
      maxima of calcium 40 mEq/L and phosphates 40 mM/L were tested. The samples were
      evaluated by visual observation with the unaided eye and with a Tyndall beam to
      accentuate the visibility of small particles and low-level turbidity. The
      turbidity and particle content of samples not exhibiting visible particles or
      haze were measured electronically. Evaluations were performed initially and after
      24 and 48 hours of storage at 23 deg C and 37 deg C. Samples were also stored for
      30 days at 4 deg C, were warmed at room temperature, and were evaluated after
      warming and after additional storage of 24 and 48 hours at room temperature. The
      addition of cysteine hydrochloride injection 5 mL/L for each 1% of amino acids
      content reduced the pH of the core parenteral nutrition admixtures from 6.4 to
      5.9. The solubility of calcium and phosphates was increased by approximately 30%
      by that reduction in pH. The compatibility-incompatibility concentration ranges
      for each of the five core formulations, in which calcium ranged up to 40 mEq/L
      and phosphates ranged up to 40 mmol/L at temperatures of 23 deg C and 37 deg C
      are presented in tables and figures. The addition of cysteine hydrochloride 0.5
      mL (25 mg) per gram of amino acids from FreAmine III increased the solubility of
      calcium and phosphates about 30% by lowering the solution pH. 

PMID- 23979511
TI  - PostScription: Future Trends in High-Technology Pharmaceutical Compounding.

PMID- 23979512
TI  - Synthesis, anti-inflammatory, and antiproliferative activity evaluation of
      isoindole, pyrrolopyrazine, benzimidazoisoindole, and benzimidazopyrrolopyrazine
      derivatives.
AB  - A number of isoindole (3x, 3y, 6xa-6ye), pyrrolopyrazine (3z, 6za-6ze),
      benzimidazoisoindole (4x, 4y, 7xa-7ye), and benzimidazopyrrolopyrazine (4z, 7za
      7ze) derivatives has been synthesized in excellent yields. All these compounds
      were fully characterized and evaluated against five human cancer cell lines for
      their anti-inflammatory and antiproliferative activity. Compounds 6yc and 7zd
      exhibited good anti-inflammatory activity whereas compounds 6zc, 7zd (lung NCl H
      522), 6ye, 7xd, 7yd, 7zc, 7zd (colon HCT-15), 6xc, 7zc (ovary PA-1), 6xc, 6yb,
      6zc (liver HepG-2) exhibited good antiproliferative activity. 

PMID- 23979513
TI  - Flow cytometric analysis of bimolecular fluorescence complementation: a high
      throughput quantitative method to study protein-protein interaction.
AB  - Among methods to study protein-protein interaction inside cells, Bimolecular
      Fluorescence Complementation (BiFC) is relatively simple and sensitive. BiFC is
      based on the production of fluorescence using two non-fluorescent fragments of a
      fluorescent protein (Venus, a Yellow Fluorescent Protein variant, is used here).
      Non-fluorescent Venus fragments (VN and VC) are fused to two interacting proteins
      (in this case, AKAP-Lbc and PDE4D3), yielding fluorescence due to VN-AKAP-Lbc-VC
      PDE4D3 interaction and the formation of a functional fluorescent protein inside
      cells. BiFC provides information on the subcellular localization of protein
      complexes and the strength of protein interactions based on fluorescence
      intensity. However, BiFC analysis using microscopy to quantify the strength of
      protein-protein interaction is time-consuming and somewhat subjective due to
      heterogeneity in protein expression and interaction. By coupling flow cytometric
      analysis with BiFC methodology, the fluorescent BiFC protein-protein interaction
      signal can be accurately measured for a large quantity of cells in a short time.
      Here, we demonstrate an application of this methodology to map regions in PDE4D3
      that are required for the interaction with AKAP-Lbc. This high throughput
      methodology can be applied to screening factors that regulate protein-protein
      interaction.

PMID- 23979515
TI  - Spiropyran-based dynamic materials.
AB  - In the past few years, spiropyran has emerged as the molecule-of-choice for the
      construction of novel dynamic materials. This unique molecular switch undergoes
      structural isomerisation in response to a variety of orthogonal stimuli, e.g.
      light, temperature, metal ions, redox potential, and mechanical stress.
      Incorporation of this switch onto macromolecular supports or inorganic scaffolds
      allows for the creation of robust dynamic materials. This review discusses the
      synthesis, switching conditions, and use of dynamic materials in which spiropyran
      has been attached to the surfaces of polymers, biomacromolecules, inorganic
      nanoparticles, as well as solid surfaces. The resulting materials show
      fascinating properties whereby the state of the switch intimately affects a
      multitude of useful properties of the support. The utility of the spiropyran
      switch will undoubtedly endow these materials with far-reaching applications in
      the near future. 

PMID- 23979514
TI  - Experimental and computational analysis of the secretome of the hyperthermophilic
      archaeon Pyrococcus furiosus.
AB  - Although Pyrococcus furiosus is one of the best studied hyperthermophilic
      archaea, to date no experimental investigation of the extent of protein secretion
      has been performed. We describe experimental verification of the extracellular
      proteome of P. furiosus grown on starch. LC-MS/MS-based analysis of culture
      supernatants led to the identification of 58 proteins. Fifteen of these proteins
      had a putative N-terminal signal peptide (SP), tagging the proteins for
      translocation across the membrane. The detected proteins with predicted SPs and
      known function were almost exclusively involved in important extracellular
      functions, like substrate degradation or transport. Most of the 43 proteins
      without predicted N-terminal signal sequences are known to have intracellular
      functions, mainly (70 %) related to intracellular metabolism. In silico analyses
      indicated that the genome of P. furiosus encodes 145 proteins with N-terminal
      SPs, including 21 putative lipoproteins and 17 with a class III peptide. From
      these we identified 15 (10 %; 7 SPI, 3 SPIII and 5 lipoproteins) under the
      specific growth conditions of this study. The putative lipoprotein signal
      peptides have a unique sequence motif, distinct from the motifs in bacteria and
      other archaeal orders. 

PMID- 23979516
TI  - p38 mitogen-activated protein kinase mediates hyperosmolarity-induced
      vasoconstriction through myosin light chain phosphorylation and actin
      polymerization in rat aorta.
AB  - Hyperosmotic stress induces the contractile response of vascular smooth muscle
      cells (VSMCs). Previous studies have demonstrated that cytoskeleton
      reorganization and Rho/Rho-kinase-mediated inactivation of myosin light chain
      phosphatase (MLCP) play an important role in hyperosmotic vasoconstriction, but
      the precise mechanism is unknown. This study aimed to investigate the contractile
      response of endothelium-denuded rings of rat aortas to hyperosmolar sucrose (160
      mM) in the presence or absence of inhibitors for various protein kinases. We
      found that the hyperosmotic constriction of aortic rings was attenuated not only
      by ML-7 or hydroxyfasudil, specific inhibitor for myosin light chain kinase
      (MLCK) or Rho-kinase, respectively, but also by SB203580, a specific inhibitor
      for p38 mitogen-activated kinase (p38 MAPK). Hyperosmolar sucrose evoked a
      transient increase in cytosolic free Ca(2+) in rat VSMCs, and this response was
      not affected by SB203580. Western blot analysis of proteins extracted from rings
      showed that the hyperosmolar sucrose stimulated phosphorylation of the Rho-kinase
      mediated myosin phosphatase target subunit 1, myosin light chain (MLC), and p38
      MAPK. The experiments performed using a combination of the kinase inhibitors
      showed that hyperosmolarity-induced MLC phosphorylation is partially mediated via
      the SB203580-sensitive pathway and is independent of both MLCK and Rho-kinase
      mediated inactivation of MLCP. Furthermore, the hyperosmolarity-induced increase
      in the F-actin/G-actin ratio in rings was attenuated not only by hydroxyfasudil
      but also by SB203580. These results suggest that p38 MAPK is involved in
      hyperosmotic vasoconstriction via stimulation of MLC phosphorylation and
      cytoskeleton reorganization through pathways independent of activation of MLCK
      and/or Rho-kinase-mediated mechanisms. 

PMID- 23979517
TI  - Alignment in total knee arthroplasty, still more questions than answers....

PMID- 23979518
TI  - Comparison of custom to standard TKA instrumentation with computed tomography.
AB  - PURPOSE: There is conflicting evidence whether custom instrumentation for total
      knee arthroplasty (TKA) improves component position compared to standard
      instrumentation. Studies have relied on long-limb radiographs limited to two
      dimensional (2D) analysis and subjected to rotational inaccuracy. We used
      postoperative computed tomography (CT) to evaluate preoperative three-dimensional
      templating and CI to facilitate accurate and efficient implantation of TKA
      femoral and tibial components. METHODS: We prospectively evaluated a single
      surgeon cohort of 78 TKA patients (51 custom, 27 standard) with postoperative CT
      scans using 3D reconstruction and contour-matching technology to preoperative
      imaging. Component alignment was measured in coronal, sagittal and axial planes.
      RESULTS: Preoperative templating for custom instrumentation was 87 and 79 %
      accurate for femoral and tibial component size. All custom components were within
      1 size except for the tibial component in one patient (2 sizes). Tourniquet time
      was 5 min longer for custom (30 min) than standard (25 min). In no case was
      custom instrumentation aborted in favour of standard instrumentation nor was
      original alignment of custom instrumentation required to be adjusted
      intraoperatively. There were more outliers greater than 2 degrees  from intended
      alignment with standard instrumentation than custom for both components in all
      three planes. Custom instrumentation was more accurate in component position for
      tibial coronal alignment (custom: 1.5 degrees  +/- 1.2 degrees ; standard: 3
      degrees  +/- 1.9 degrees ; p = 0.0001) and both tibial (custom: 1.4 degrees  +/-
      1.1 degrees ; standard: 16.9 degrees  +/- 6.8 degrees ; p < 0.0001) and femoral
      (custom: 1.2 degrees  +/- 0.9 degrees ; standard: 3.1 degrees  +/- 2.1 degrees ;
      p < 0.0001) rotational alignment, and was similar to standard instrumentation in
      other measurements. CONCLUSIONS: When evaluated with CT, custom instrumentation
      performs similar or better to standard instrumentation in component alignment and
      accurately templates component size. Tourniquet time was mildly increased for
      custom compared to standard.

PMID- 23979519
TI  - Palpation tests versus impingement tests in Neer stage I and II subacromial
      impingement syndrome.

PMID- 23979520
TI  - Combinatorial drug screening identifies synergistic co-targeting of Bruton's
      tyrosine kinase and the proteasome in mantle cell lymphoma.

PMID- 23979522
TI  - Overexpression of SNORD114-3 marks acute promyelocytic leukemia.

PMID- 23979521
TI  - Clonal evolution in hematological malignancies and therapeutic implications.
AB  - The ability of cancer to evolve and adapt is a principal challenge to therapy in
      general and to the paradigm of targeted therapy in particular. This ability is
      fueled by the co-existence of multiple, genetically heterogeneous subpopulations
      within the cancer cell population. Increasing evidence has supported the idea
      that these subpopulations are selected in a Darwinian fashion, by which the
      genetic landscape of the tumor is continuously reshaped. Massively parallel
      sequencing has enabled a recent surge in our ability to study this process,
      adding to previous efforts using cytogenetic methods and targeted sequencing.
      Altogether, these studies reveal the complex evolutionary trajectories occurring
      across individual hematological malignancies. They also suggest that while clonal
      evolution may contribute to resistance to therapy, treatment may also hasten the
      evolutionary process. New insights into this process challenge us to understand
      the impact of treatment on clonal evolution and inspire the development of novel
      prognostic and therapeutic strategies. 

PMID- 23979523
TI  - Epigenetic mechanisms of protein tyrosine phosphatase 6 suppression in diffuse
      large B-cell lymphoma: implications for epigenetic therapy.
AB  - Protein tyrosine phosphatases such as PTPN6 can be downregulated in various
      neoplasms. PTPN6 expression by immunohistochemistry in 40 diffuse large B-cell
      lymphoma (DLBCL) tumors was lost or suppressed in 53% (21/40). To elucidate the
      molecular mechanisms of PTPN6 suppression, we performed a comprehensive
      epigenetic analysis of PTPN6 promoter 2 (P2). None of the DLBCL primary tumors
      (0/37) had PTPN6 hypermethylation on the CpG1 island using methylation-specific
      PCR, pyrosequencing, and high-resolution melting assays. However,
      hypermethylation in 57% (21/37) of cases was found in a novel CpG island (CpG2)
      in P2. PTPN6 gene suppression was reversed by 5-aza-deoxycytidine (5-Aza), a DNA
      methyltransferase inhibitor, and the histone deacetylase inhibitor (HDACi)
      LBH589. LBH589 and 5-Aza in combination inhibited DLBCL survival and PTPN6
      hypermethylation at CpG2. The role of histone modifications was investigated with
      a chromatin-immunoprecipitation assay demonstrating that PTPN6 P2 is associated
      with silencing histone marks H3K27me3 and H3K9me3 in DLBCL cells but not normal B
      cells. 3-Deazaneplanocin A, a histone methyltransferase inhibitor, decreased the
      H3K27me3 mark, whereas HDACi LBH589 increased the H3K9Ac mark within P2 resulting
      in re-expression of PTPN6. These studies have uncovered novel epigenetic
      mechanisms of PTPN6 suppression and suggest that PTPN6 may be a potential target
      of epigenetic therapy in DLBCL. 

PMID- 23979524
TI  - Letting wet spots be wet: restoring natural bioreactors in the dissected glacial
      landscape.
AB  - In this paper, we argue that there is tremendous potential for nitrate-N
      reductions to occur throughout the Corn Belt region of the USA if we simply let
      naturally occurring wet spots on the landscape be wet. Geologic and hydrologic
      data gathered in the Walnut Creek watershed located in south-central Iowa
      provides compelling evidence that substantial nutrient-processing capacity exists
      in this dissected glacial landscape. Self-similarity of stratigraphy,
      sedimentology and hydrology observed at all spatial scales in the watershed
      suggests that Holocene alluvial fill deposits provide a natural bioreactor for
      denitrification of upland groundwater nitrate-N; the occurrence of such deposits
      can be mapped to identify potential nitrogen sinks across the landscape. This
      approach to identifying potential nitrogen sinks is geology focused and extends
      potential locations for nutrient processing upstream into the headwater
      catchments of individual fields. 

PMID- 23979525
TI  - Does external funding help adaptation? Evidence from community-based water
      management in the Colombian Andes.
AB  - Despite debate regarding whether, and in what form, communities need external
      support for adaptation to environmental change, few studies have examined how
      external funding impacts adaptation decisions in rural resource-dependent
      communities. In this article, we use quantitative and qualitative methods to
      assess how different funding sources influence the initiative to adapt to water
      scarcity in the Colombian Andes. We compare efforts to adapt to water scarcity in
      111 rural Andean communities with varied dependence on external funding for water
      management activities. Findings suggest that despite efforts to use their own
      internal resources, communities often need external support to finance adaptation
      strategies. However, not all external financial support positively impacts a
      community's abilities to adapt. Results show the importance of community-driven
      requests for external support. In cases where external support was unsolicited,
      the results show a decline, or "crowding-out," in community efforts to adapt. In
      contrast, in cases where communities initiated the request for external support
      to fund their own projects, findings show that external intervention is more
      likely to enhance or "crowds-in" community-driven adaptation. 

PMID- 23979526
TI  - Mild acute ischaemic stroke--the case for thrombolytic therapy.
AB  - The incidence of acute ischaemic stroke with mild neurological deficits (called
      mild ischaemic stroke [MIS]) is increasing, and studies show that a large
      percentage of untreated patients have poor long-term outcomes. Many physicians do
      not, however, routinely treat patients with MIS with intravenous recombinant
      tissue plasminogen activator (rtPA)--the only thrombolytic therapy currently
      approved by the FDA. Here, we discuss the reasons why physicians do not treat
      patients with MIS and we review the studies published to date regarding the
      potential risks and benefits of administering rtPA in this patient population. We
      then provide our perspective on why patients with MIS should be treated with
      intravenous rtPA and we highlight the need for a randomized clinical trial to
      address treatment of MIS.

PMID- 23979527
TI  - Pain: Comorbidity of neuropathic pain and migraine in patients with multiple
      sclerosis.

PMID- 23979528
TI  - Known unknowns and unknown unknowns at the point of care.

PMID- 23979529
TI  - Drugs for sexually transmitted infections.

PMID- 23979530
TI  - Natural birth-induced UCP2 in brain development.
AB  - The prevalence of convenience-driven delivery via Caesarian-section (C-section)
      has been steadily increasing in Western as well as in developing societies.
      Today, significantly more deliveries occur via surgical means than medical
      necessity mandates. Despite tremendous advances in surgical techniques and pre-
      and post-operative surgical care, there remains to be limited understanding on
      the physiological influence of vaginal birth with particular emphasis on long
      term outcome on the offspring. Serendipitously, we recently uncovered in mice
      that vaginal birth induces significantly higher level of Ucp2 mRNA expression in
      the hippocampus than experimental C-section. We showed that during the early
      postnatal period, UCP2 expression promotes neuronal differentiation, axonal
      outgrowth and synapse formation in the hippocampus. We also observed that Ucp2
      knockout animals show adult behaviors associated with the hippocampal formation
      that is different from wild type littermates. Taken together these observations
      suggest that vaginal birth may play a crucial role in determining adult brain
      structure and function that is different from that of the effect of surgically
      assisted birth. 

PMID- 23979531
TI  - The major European dietary patterns and metabolic syndrome.
AB  - Metabolic syndrome (MetS) is a cluster of risk factors that significantly
      increases the risk of cardiovascular disease. The lack of universally accepted
      diagnosis criteria makes it difficult to know the real prevalence of MetS in both
      adult and pediatric population. Lifestyle, especially nutritional habits and
      physical activity, have been suggested to be independent risk factors for the
      development of MetS. Recent studies highlight the need to prioritize overall
      dietary patterns, rather than isolated nutrients, to better appraise the
      associations between nutritional habits and MetS. In this review we summarize
      recently published intervention trials and systematic reviews that evaluated the
      association between overall dietary patterns and the risk of MetS. Westernized
      dietary patterns, characterized by a high consumption of meat or meat products,
      snacks, baked desserts and sugar-sweetened beverages, which provide high amounts
      of saturated fatty acids and simple carbohydrates as added sugars, have been
      associated with higher risk of MetS. In contrast, more traditional dietary
      patterns, including the Mediterranean dietary pattern (MDP), characterized by a
      high consumption of vegetables, fruits, whole cereals and fish are associated
      with a reduced risk of MetS. The main characteristics of the MDP include a high
      consumption of nuts and olive oil, resulting in a relatively fat-rich pattern
      that provides high amounts of mono- and polyunsaturated fatty acids, bioactive
      polyphenols and dietary fiber. Strong evidence is accumulating to support that a
      closer conformity with the MDP is inversely associated with the incidence of
      MetS, cardiovascular risk factors, diabetes and cardiovascular disease. 

PMID- 23979533
TI  - Ecotoxicity of pp'DDE to Daphnia magna.
AB  - pp'-Dichlorodiphenyl-dichloroethylene (pp'DDE), a metabolite of pp'
      dichlorodiphenyl-trichloroethane poses a risk for many ecosystems in spite of the
      banning of the parent compound because of its persistence and bioaccumulability.
      Nevertheless, the knowledge of acute and chronic toxicity on aquatic organisms is
      still very poor. In the present study, Daphnia magna was exposed to varying
      concentrations of pp'DDE in water and through diet to determine both acute
      toxicity and potential for effects on reproduction and survivability. The 48 h
      IC50 was 5.08 MUg L(-1) (3.76-7.01 MUg L(-1)). As pp'DDE concentration in water
      was not stable and the amount assumed by food cannot be established with
      certainty, the results of chronic toxicity tests were expressed as the
      concentration in the organism which caused a negative effect. Grazing activity
      was affected with a pp'DDE concentration in the organism of 24 ng mg(-1) d.w.,
      while the lowest observed effect concentration for fecundity reduction was 109 ng
      mg(-1) d.w.

PMID- 23979534
TI  - A quick investigation of the detrimental effects of environmental pollutant
      polycyclic aromatic hydrocarbon fluoranthene on the photosynthetic efficiency of
      wheat (Triticum aestivum).
AB  - The present study describes the effects of polycyclic aromatic hydrocarbon
      pollutant fluoranthene (FLT) on photochemical efficiency of plants and hence
      their growth. Chlorophyll a fluorescence measurements were performed in order to
      get quick and reliable information about the effects of fluoranthene. The number
      of active reaction centres decreased by more than 20% in FLT treated samples. The
      results show that FLT affects the overall primary photochemistry by inhibiting
      the number of active reaction centres (RC) while the efficiency of each of the
      active reaction centres is not affected. We propose that the effect of
      fluoranthene is mainly on the absorption and trapping of the light energy by the
      RC rather than the actual electron transport. The results may be applicable to a
      wide range of plants provided other environmental and physiological conditions
      are taken into account carefully.

PMID- 23979535
TI  - Identification of sex pheromone components of blueberry spanworm Itame
      argillacearia (Lepidoptera: Geometridae).
AB  - Blueberry spanworm, Itame argillacearia (Packard), is an important defoliator of
      lowbush (syn. 'wild') blueberry, Vaccinium angustifolium Aiton, in north-eastern
      North America. The goal of the present study was to identify the female I.
      argillacearia sex pheromone, which could be used in traps for monitoring or mass
      trapping this pest. Gas chromatography/mass spectrometry (GC/MS) and
      electroantennogram (EAG) recordings of sex pheromone gland extracts, in
      combination with chemical synthesis, a Y-tube olfactometer study and field
      experiments confirmed (2R,3S)-2-ethyl-3-((Z,Z)-tridecadi-2,5-enyl) oxirane
      (hereafter (Z,Z)-(3R,4S)-3,4-epoxy-6,9-heptadecadiene) and (Z,Z,Z)-3,6,9
      heptadecatriene as female-produced sex pheromone components. (Z,Z)-(3R,4S)-3,4
      Epoxy-6,9-heptadecadiene elicited a response from male I. argillacearia antennae
      during EAG recording, and in the Y-tube olfactometer tests males did not
      discriminate between a live female and (Z,Z)-(3R,4S)-3,4-epoxy-6,9
      heptadecadiene. Field-trapping experiments showed that a blend of (Z,Z)-(3R,4S)
      3,4-epoxy-6,9-heptadecadiene and (Z,Z,Z)-3,6,9-heptadecatriene was more
      attractive to male moths than (Z,Z)-(3R,4S)-3,4-epoxy-6,9-heptadecadiene alone. 

PMID- 23979536
TI  - The choice of reference gene set for assessing gene expression in barley (Hordeum
      vulgare L.) under low temperature and drought stress.
AB  - Drought and low temperature are the two most significant causes of abiotic stress
      in agricultural crops and, therefore, they pose considerable challenges in plant
      science. Hence, it is crucial to study response mechanisms and to select genes
      for identification signaling pathways that lead from stimulus to response. The
      assessment of gene expression is often attempted using real-time RT-PCR (qRT
      PCR), a technique which requires a careful choice of reference gene(s) for
      normalization purpose. Here, we report a comparison of 13 potential reference
      genes for studying gene expression in the leaf and crown of barley seedlings
      subjected to low temperature or drought stress. All three currently available
      software packages designed to identify reference genes from qRT-PCR data (GeNorm,
      NormFinder and BestKeeper) were used to identify informative sets of up to three
      reference genes. Interestingly, the data obtained from the separate treatment of
      leaf and crown have led to the recommendations that HSP70 and S-AMD (and possibly
      HSP90) to be used as the reference genes for low-temperature stressed leaves,
      HSP90 and EF1alpha for low-temperature stressed crowns, cyclophilin and ADP-RF
      (and possibly ACT) for drought-stressed leaves, and EF1alpha and S-AMD for
      drought-stressed crowns. Our results have demonstrated that the gene expression
      can be highly tissue- or organ-specific in barley and have confirmed that
      reference gene choice is essential in qRT-PCR. The findings can also serve as
      guidelines for the selection of reference genes under different stress conditions
      and lay foundation for more accurate and widespread use of qRT-PCR in barley gene
      analysis. 

PMID- 23979537
TI  - PostScription: Sterile Product Admixture Preparation.

PMID- 23979538
TI  - Legal and ethical issues for pharmacy websites.

PMID- 23979539
TI  - Panel discussion: prohormones.

PMID- 23979540
TI  - Veterinary transdermal medication: a to z.

PMID- 23979541
TI  - Autoclaves for the sterilization of compounded parenteral products.

PMID- 23979542
TI  - Barcode system and computerized balance speed compounding and enhance accuracy.

PMID- 23979543
TI  - Accuracy of small-volume containers.

PMID- 23979544
TI  - Basics of compounding for terrorist attacks, part2.

PMID- 23979545
TI  - Stability of Clindamycin Phosphate in AutoDose Infusion System Bags.
AB  - The physical and chemical stability of clindamycin phosphate 600mg/100mL and
      1.2g/100mL admixed in 0.9% sodium chloride injection packaged in AutoDose
      Infusion System Bags was evaluated. Triplicate test samples were prepared by
      bringing the required amount of clindamycin phosphate injection to volume with
      0.9% sodium chloride injection. A total of 100 mL of each of the test solutions
      was packaged in each of three ethylene vinyl acetate AutoDose bags designed for
      use in the AutoDose Infusion System. Samples were stored protected from light and
      were evaluated at appropriate intervals for up to 30 days at 4 deg C and up to 7
      days at 23 deg C. Physical stability was assessed using a multistep evaluation
      procedure that included both turbidimetric and particulate measurement, as well
      as visual inspection. Chemical stability was assessed initially and at
      appropriate intervals during the study periods with stability-indicating high
      performance liquid chromatographic anyalytical techinique based on the
      determination of drug concentrations. Throughout the study, the admixtures were
      clear and colorless when viewed in normal fluorescent room light and with a
      Tyndall beam. Measured turbidity and particulate content were low initially and
      exhibited little change throughout the study. The clindamycin phosphate samples
      exhibited no increase in measured particulates during the study period. High
      performance liquid chromatographic analysis found little or no decomposition in
      the samples, and the analysis indicated that clindamycin phosphate in the test
      admixtures remained stable for 30 days at 4 deg C and for 7 days at 23 deg C. The
      clindamycin phosphate admixtures exhibited physical and chemical stability
      consistent with previous studies. The AutoDose Infusion System bags were not
      found to have an adverse effect on the physical and chemical stability of this
      drug. 

PMID- 23979546
TI  - Chemical stability of cefazolin sodium after reconstituting in 0.9% sodium
      chloride injection and storage in polypropylene syringes for pediatric use.
AB  - A stability-indicating high-performance liquid chromatographic assay method was
      used to study the stabililty of cefazolin sodium (50mg/mL) in 0.9% sodium
      chloride injection in polypropylene syringes at 5 deg C and 25 deg C. The
      concentrations of the drug were directly related to peak heights, and the percent
      relative standard deviation based on five injections was 0.5. There were three
      products of decomposition that separated from the intact drug. At 5 deg C, the
      decomposition was less than 4% when stored for 22 days; and at 25 deg C, the loss
      in potency was less than 8% when stored for 7 days. When the drug was stored for
      22 days at 5 deg C, its pH value increased from 5.1 to 5.3. The pH value of the
      injection increased from 5.1 to 5.8 when stored at 25 deg C for 7 days. The drug
      was not adsorbed onto the syringes, and the physical appearance of the injetion
      remained clear at 5 deg C and at 25 deg C during the study period. 

PMID- 23979547
TI  - Quantification of total dexamethasone phosphate delivery by iontophoresis.
AB  - The total amount of dexamethasone phosphate transferred into the human body as a
      function of iontophoresis has not previously been determined, despite its
      widespread clinical use in the treatment of localized inflammation. The objective
      of this study was to document the optimal parameters required for clinical
      iontophoresis of dexamethasone phophate. Results were achieved by the experiment
      of in vitro evalutations of dexamethasone phosphate iontophoresis and by in vivo
      estimations of drug amounts (milligrams) iontophoresed into healthy human
      volunteers. The in vitro evaluations were conducted to quantify total
      dexamethasone phosphate amounts transferred as a function of dosage (milliAmp
      minutes), to evaluate the efficiency of the delivery based on dexamethasone
      phosphate only (pure) donor solutions compared with dexamethasone phosphate +
      salts (coformulated) donor solutions, and to compare the delivery from the
      negative electrode (cathode) with that from the positive electrode (amode). The
      in vivo drug amounts were estimated by the use of the formulation conditions
      determined from the in vivo testing. The in vitro evaluations were conducted with
      side-by-side glass diffusion cells, which measured iontophoretic and passive
      delivery across an ultrafiltration membrane. The in vivo experiments were
      conducted on five healthy human volunteers who were wearing a low-voltage
      iontophoreses system. Total drug delivery was ascertained by the difference
      between the initial drug load and a final residual amount determined by
      extraction. The in vitro results demonstrated increased dexamethasone phosphate
      delivery with higher iontophoretic dosages and with the pure dexamethasone
      phosphate formulation. Delivery from the anode was significantly lower than that
      from the cathode. After an 80-mA-minute drug-delivery was administered, the in
      vivo iontophoretic delivery was measured to be 1.40 +/- 0.23 mg, and the
      corresponding passive delivery was 0.26 +/-0.16 mg. The in vitro experiments
      confirm iontophoretic delivery of dexamethasone phosphate across artificial
      membranes, and the in vivo experiments suggest that drug is delivered into human
      skin. 

PMID- 23979548
TI  - Enantioselective synthesis of 3-hydroxy oxindoles by ytterbium-catalysed
      decarboxylative addition of beta-ketoacids to isatins.
AB  - A ytterbium(III)-indapybox catalysed enantioselective decarboxylative addition
      reaction of beta-ketoacids to isatins is described. The biologically important 3
      hydroxy oxindoles were obtained in high yields and excellent
      enantioselectivities.

PMID- 23979549
TI  - [Tertiary syphilis diagnosed in a psychiatric unit in Buenos Aires, XXI century].
AB  - It is a common belief that syphilis, since its effective treatment, is
      eradicated. However, because of failure prevention and control it is still
      present. Therefore, we describe what happened in our service with a young patient
      who was admitted with a presumptive diagnosis of delusional syndrome with a
      history of multiple symptoms and signs that led him to wander around different
      specialties in many hospitals. Semiology led us to think of neurosyphilis which
      was confirmed by laboratory tests on blood and cerebrospinal fluid. Due was then
      applied in addition to psychiatric treatment for syphilis, but despite this, the
      patient had a torpid evolution given the lateness of his picture. In this paper
      we wish to make a warning to doctors about the need to consider when framing
      neurosyphilis differential diagnosis and thus avoid the progression of the
      disease. 

PMID- 23979550
TI  - [Screening for symptoms of depression during postpartum and the long term follow
      up: temporal stability and associated factors].
AB  - AIMS: To describe the frequency of depressive symptoms compatible with a
      postpartum depression diagnosis, the associated factors and the temporal
      stability. METHODS: During 2006-2007 398 hospitalized puerperal women who
      attended CEMIC were interviewed 5 days after childbirth using the Edinburgh
      Postnatal Depression Scale and a socio-demographic questionnaire. A logistic
      regression analysis was performed to identify associated factors with a positive
      screening. During the following 6-12 months a follow up was carried with two
      groups of similar characteristics. RESULTS: The frequency of depressive symptoms
      at post partum was 17.8% (cut off = 10). Depressive history and neonatal
      intensive care were significantly related to a positive screening. From the 110
      interviewed women, 24 were positive in the follow-up. CONCLUSION: The prevalence
      of risk for postpartum depression in the sample of patients surveyed is within
      the parameters reported in international literature. At the 6 month follow up, 6
      previously asymptomatic women during the first screening turned on positive. It
      is theorize the existence of potential postpartum depression cases that can
      manifest up to a year after childbirth.

PMID- 23979551
TI  - [Depressive pseudodementia. Differential diagnosis or meeting point?].
AB  - Depressive pseudodementia is a major depressive disorder in which the cognitive
      deficits secondary to the affective disorder is so significant that clinicians
      are obliged to consider dementia as a differential diagnosis. The relationship
      between depression and dementia is complex and intricate. Even after depressive
      pseudodementia has remitted, certain cognitive deficits may persist and the risk
      of developing dementia increases. The concept of depressive pseudodementia
      continues to be useful in clinical practice in spite of its limitations. 

PMID- 23979552
TI  - [Neuropsychiatric non motor symptoms of Parkinson's disease].
AB  - In the last decade we have witnessed substantial progress towards the
      understanding of Parkinson's disease. According to pathological and neuroimaging
      studies, the traditional view of Parkinson's disease that begins with the
      development of motor symptoms such as bradykinesia, rigidity and tremor, has
      begun to change. It is now understood that there would be a "premotor" or
      "preclinical" period in which the alphasynuclein pathology begins outside of the
      substantia nigra in the lower brainstem and autonomic nervous system. Although
      the pathophysiology of this phase is still unclear, it is currently thought that
      its symptoms would correspond to the so-called "non-motor symptoms". Hyposmia,
      depression, constipation and REM sleep disorders are one of the most relevant non
      motor symptoms at this "premotor" stage. The spectrum of non-motor symptoms is
      very broad and covers the domains of neuropsychiatric, dysautonomic,
      gastrointestinal and sensory symptoms as well as sleep disorders.
      Neuropsychiatric symptoms such as depression, impulse control disorder, psychosis
      and dementia, are a major cause of disability as they are directly related to
      quality of life. 

PMID- 23979553
TI  - [Diabetes, alexithymia and depression].
AB  - Diabetes Mellitus and Depression are two increasing pathologies. Several articles
      indicate that Depression in Diabetes is twice as important as in the general
      population. Yet, Depression in diabetic patients is underdiagnosed. On the other
      hand, Alexithymia might be a factor associated to Depression. We therefore
      carried out a research in order to evaluate the relationship between Depression
      and Alexithymia in diabetic patients at the Italian Hospital of Buenos Aires. We
      performed psychiatric interviews, which led to diagnoses based on DSM-IV, and
      applied the following scales: HAM-D, TAS-26, DBI and M.I.N.I. We evaluated 59
      patients who had been diagnosed Type II Diabetes. Crossing variables, we observed
      a negative correlation between the results of Beck's Depression Inventory and
      those of Hamilton's Depression Scale. On the contrary, these last results showed
      a positive correlation with results obtained through TAS-26, which reveals a
      significant relationship between Depression and the presence of Alexithymia.
      According to the link between Depression, Diabetes Mellitus II and Alexithymia
      and considering that Alexithymia has consequences on the illness evolution and
      the treatment of both pathologies, it seems important to determine when and how
      to include its evaluation. 

PMID- 23979554
TI  - [Heart failure and depression. A psychosocial perspective].
AB  - Heart failure is the final stage of many heart diseases and the main cause of
      mortality. It affects the patient, the family and the health system. Depression
      affects between the 13.9% and 75% of inpatients, and between 11% and 42% of
      outpatients. It also affects social life and quality of life, causes
      hospitalization and rehospitalization, and it activates biological mechanisms
      that worsen the evolution of heart diseases. From a bibliographic review we
      discuss psychosocial and biological aspects that relate both diseases. 

PMID- 23979555
TI  - [A chip off the old block? Clinical genetics approach in the practice of
      psychiatric consultation].
AB  - Psychiatry and Genetics are known to have an increasingly tighter bond with each
      other, which drives professionals the need to stay focused and updated. We use
      case studies as the means to link theoretical concepts with daily work. By doing
      so, we hope to provide psychiatrists some of the most necessary tools that will
      help them identify the need to consult a Genetic Counselor while treating a
      patient. This will certainly help diagnose patients and offer them the adequate
      treatment, whenever applicable. Patients and their families will also benefit
      from the possibility of receiving the appropriate counseling. 

PMID- 23979556
TI  - [Medical comorbidity in psychiatric disorders].
AB  - Understand that in addition to the problems inherent to mental conditions the
      people suffer associated medical conditions that further complicate their
      condition and endanger its vitality is paramount. Of course this requires
      fundamental premise construct understanding of mental health within the medical
      model of care. As mentioned above we make the following literature review
      focusing on understanding the interaction between depression and cardiovascular
      disease mainly and reviewing other comorbidities and their impact on our
      patients. We show also that several factors contribute to poor physical health of
      people with psychiatric disorders including different individual choices in
      lifestyle determined by its pathologies and on the other hand a marked disparity
      in access, utilization and health care provision.

PMID- 23979557
TI  - [Wilhelm Stekel and the origins of the psychoanalytical research on anguish].

PMID- 23979558
TI  - [Nervous states of anguish and their treatment].

PMID- 23979559
TI  - Protein purification-free method of binding affinity determination by microscale
      thermophoresis.
AB  - Quantitative characterization of protein interactions is essential in practically
      any field of life sciences, particularly drug discovery. Most of currently
      available methods of KD determination require access to purified protein of
      interest, generation of which can be time-consuming and expensive. We have
      developed a protocol that allows for determination of binding affinity by
      microscale thermophoresis (MST) without purification of the target protein from
      cell lysates. The method involves overexpression of the GFP-fused protein and
      cell lysis in non-denaturing conditions. Application of the method to STAT3-GFP
      transiently expressed in HEK293 cells allowed to determine for the first time the
      affinity of the well-studied transcription factor to oligonucleotides with
      different sequences. The protocol is straightforward and can have a variety of
      application for studying interactions of proteins with small molecules, peptides,
      DNA, RNA, and proteins.

PMID- 23979560
TI  - Theoretical investigations on the mechanistic pathway of the thermal
      rearrangement of substituted N-acyl-2,2-dimethylaziridines.
AB  - The mechanism of the thermal rearrangement of substituted N-acyl-2,2
      dimethylaziridines 1 has been studied using quantum chemistry methods. Geometries
      of reactants, transition states and products have been optimized at the B3LYP/6
      311++G(2d,2p) level. Relative energies for various stationary points have been
      determined and reaction identified by IRC calculations. The results show that
      thermal rearrangements occur in three ways. Firstly, the transition state TS 1 in
      which a hydrogen atom of methyl groups migrates from primary carbon to oxygen of
      amid group to give the N-methallylamide 2. The second is via the transition state
      TS 2 in which the attack of oxygen to the tertiary carbon yields the oxazoline 3.
      The third is via the transition state TS 3 in which a hydrogen migrate from the
      secondary carbon to oxygen to give the vinylamide 4. In order to get insights
      into the factors determining the exact nature of its interactions with
      electrophiles, the application of reactivity parameters derived from density
      functional theory in a local sense, in particular the softness and Fukui
      function, to interpret and predict the mechanisms of the thermal decomposition of
      the N-acyl-2,2-dimethylaziridines 1, has been discussed.

PMID- 23979561
TI  - Genes from the exo-xis region of lambda and Shiga toxin-converting bacteriophages
      influence lysogenization and prophage induction.
AB  - The exo-xis region, present in genomes of lambdoid bacteriophages, contains
      highly conserved genes of largely unknown functions. In this report, using
      bacteriophage lambda and Shiga toxin-converting bacteriophage phi24Beta, we
      demonstrate that the presence of this region on a multicopy plasmid results in
      impaired lysogenization of Escherichia coli and delayed, while more effective,
      induction of prophages following stimulation by various agents (mitomycin C,
      hydrogen peroxide, UV irradiation). Spontaneous induction of lambda and phi24Beta
      prophages was also more efficient in bacteria carrying additional copies of the
      corresponding exo-xis region on plasmids. No significant effects of an increased
      copy number of genes located between exo and xis on both efficiency of adsorption
      on the host cells and lytic development inside the host cell of these
      bacteriophages were found. We conclude that genes from the exo-xis region of
      lambdoid bacteriophages participate in the regulation of lysogenization and
      prophage maintenance. 

PMID- 23979562
TI  - Rasch analysis of the WHOQOL-BREF in post polio syndrome.
AB  - OBJECTIVE: The World Health Organisation quality of life abbreviated scale
      (WHOQOL-BREF) was developed as a measure of quality of life across 4 separate
      health domains; physical health, psychological, social relationships and
      environment. This study evaluated the validity of the WHOQOL-BREF in post-polio
      syndrome by testing it for fit against the Rasch model. RESULTS: The scale was
      posted to 319 volunteers, 271 (85%) completed the scale with a mean age of 66.7
      years (standard deviation 8.15); 64% were female. The social relationships domain
      fitted the Rasch model (chi2 p = 0.19) but reliability was low (alpha = 0.69) and
      there were insufficient items to test the assumption of unidimensionality.
      Solutions were derived for physical health (p = 0.45, t-test = 1.5%, alpha =
      0.67), psychological (p = 0.19, t-test = 4.9%, alpha = 0.78) and environment
      domains (p = 0.48, t-test = 6.0% - lower confidence interval 3.4%, alpha = 0.80)
      by accounting for local dependence and to cancel out differential item
      functioning. An overall measure of quality of life, which combined all 4 domains
      was validated (p = 0.80, t-test = 4.6%, alpha = 0.81). A transformation table for
      this total score is provided. CONCLUSION: The 4 domains of the WHOQOL-BREF
      provide valid measures of quality of life in post-polio syndrome. The summed
      score was more reliable and better targeted and can be used as an ordinal
      estimate of quality of life.

PMID- 23979563
TI  - Nonhongiella spirulinensis gen. nov., sp. nov., a bacterium isolated from a
      cultivation pond of Spirulina platensis in Sanya, China.
AB  - A Gram-negative, aerobic, motile rod strain, designated Ma-20(T), was isolated
      from a pool of marine Spirulina platensis cultivation, Sanya, China, and was
      subjected to a polyphasic taxonomy study. Strain Ma-20(T) can grow in the
      presence of 0.5-11 % (w/v) NaCl, 10-43  degrees C and pH 6-10, and grew optimally
      at 30  degrees C, pH 7.5-9.0 in natural seawater medium. The polar lipids were
      composed of phosphatidylethanolamine, three unidentified phospholipids and three
      unidentified polar lipids. The respiratory quinone was ubiquinone 8 (Q-8) and the
      major fatty acids were C18:1omega6c/C18:1omega7c (summed feature 8, 32.84 %),
      C16:1omega6c/C16:1omega7c (summed feature 3, 30.76 %), C16:0 (13.54 %), C12:03-OH
      (4.63 %), and C12:0 (4.09 %). The DNA G+C content of strain Ma-20(T) was 58 mol
      %. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Ma
      20(T) belonging to Gammaproteobacteria, it shared 88.46-91.55 and 89.21-91.26 %
      16S rRNA gene sequence similarity to the type strains in genus Hahella and
      Marinobacter, respectively. In addition to the large 16S rRNA gene sequence
      difference, Ma-20(T) can also be distinguished from the reference type strains
      Hahella ganghwensis FR1050(T) and Marinobacter hydrocarbonoclasticus sp. 17(T) by
      several phenotypic characteristics and chemotaxonomic properties. On the basis of
      phenotypic, chemotaxonomic and phylogenetic properties, strain Ma-20(T) is
      suggested to represent a novel species of a new genus in Gammaproteobacteria, for
      which the name Nonhongiella spirulinensis gen. nov., sp. nov. is proposed. The
      type strain is Ma-20(T) (=KCTC 32221(T)=LMG 27470(T)).

PMID- 23979564
TI  - Gender differences in patients with atrial fibrillation.
AB  - AIMS: We aimed to compare gender differences with respect to presentation of
      consecutive ambulatory patients with atrial fibrillation (AF), management of
      their disease, and outcomes. METHODS: Post-hoc analysis of an observational (non
      interventional) study performed by 616 office- and hospital-based cardiologists
      in Germany. Consecutive (mainly ambulatory) patients with Electrocardiography
      (ECG) -confirmed AF and available data from baseline (BL) and two follow-up
      visits at 6 and 12 months were assessed. RESULTS: A total of 2,742 patients
      (62.8% males, mean age 67.5 years; 37.2% women, mean age 71.2 years) were
      analysed. Women had more frequently paroxysmal and less frequently permanent AF.
      Quality of life scores were slightly worse in women compared to men, for all
      types of AF. For class III anti-arrhythmic drugs at baseline (more frequent in
      men), and for digitalis (less frequent in men at BL and 1 year) statistically
      significant differences were noted. Oral anti-coagulation (OAC) without anti
      platelet drugs was given in 67.9% at BL and in 62.7% at 1 year (no differences
      between genders). During follow-up, drug conversions in men/women were reported
      in 12.3%/14.9% (p=0.054), and electrical conversions in 14.6%/11.7% (p=0.03).
      Hospitalisations occurred in 25.9% and strokes in 3.5%. Patients with higher
      CHA2DS2-VASc scores had increased stroke rates (0, 1 and >=2 points: 0.0, 1.5 and
      3.9%, respectively; with no significant gender differences). CONCLUSION: In
      everyday management of patients with AF, there were no differences in treatment
      and major outcomes, in particular stroke, between women and men. This finding is
      opposed to earlier studies reporting OAC undertreatment of women and higher
      stroke rates.

PMID- 23979565
TI  - Can primary care physician-driven community programs address the obesity epidemic
      among high-risk populations?

PMID- 23979566
TI  - Association between renal function, diastolic dysfunction, and postoperative
      atrial fibrillation following cardiac surgery.
AB  - BACKGROUND: Renal dysfunction is associated with a higher rate of atrial
      fibrillation in clinical practice. This study investigated the associations
      between renal function, left ventricular (LV) diastolic dysfunction, and
      postoperative atrial fibrillation (POAF). METHODS AND RESULTS: A total of 265
      consecutive patients who underwent cardiac surgery were prospectively enrolled in
      the study. Echocardiography was performed before cardiac surgery. The patients
      were divided into 3 groups based on estimated glomerular filtration rate (eGFR)
      (group 1, >=90ml.min(-1).1.73m(-2); group 2, 60-90ml.min(-1).1.73m(-2); and group
      3, <60ml.min(-1).1.73m(-2)). POAF occurred in 83 of 265 patients (31.3%). The
      rate of new-onset POAF increased from 15.2% (12/79) in group 1 to 27.8% (27/97)
      in group 2 and 49.4% (44/89) in group 3 (P<0.001). Further, with increasing renal
      dysfunction from groups 1 to 3, the rate of LV diastolic dysfunction - defined as
      E/e' >15 - also increased (group 1, 19.0%; group 2, 38.1%; and group 3, 48.3%;
      P<0.001). Absolute eGFR was significantly correlated with E/e' ratio (r=-0.39,
      P<0.001). Renal function remained as the independent predictor of POAF on
      multivariate analysis (odds ratio, 1.90; 95% confidence interval: 1.26-2.87;
      P=0.002). CONCLUSIONS: In patients undergoing cardiac surgery, decreased eGFR was
      associated with an increased rate of LV diastolic dysfunction with a subsequent
      increase in the rate of POAF.

PMID- 23979567
TI  - Intimal flaps detected by optical frequency domain imaging in the proximal
      segments of native coronary arteries: an innocent bystander? Insights from the
      TROFI Trial.
AB  - BACKGROUND: The prevalence and clinical sequelae of optical frequency domain
      imaging (OFDI)-detected intimal flaps caused by vessel trauma or plaque rupture
      in the proximal native coronary arteries have not been described. METHODS AND
      RESULTS: OFDI investigation was performed following stent implantation in
      patients with ST-segment elevation myocardial infarction (STEMI). We defined a
      flap-like structure (FS) as a disruption or discontinuation of the endoluminal
      vessel surface, and classified as actual flap or artifact. FS in the left main
      stem, or maximally 20mm distal to the guiding catheter in the proximal right
      coronary artery were assessed. A total of 8,931 frames in 97 patients were
      analyzed in a frame-by-frame fashion (0.125-mm interval). OFDI identified 8 FS in
      7 patients, none of which was evident angiographically. All FS were left
      untreated because the operators per protocol were blinded to the OFDI images. A
      total of 5 FS in 5 patients (5.1%) appeared to be actual flaps in which only the
      intima was involved (mean distance from guiding catheter: 4.8+/-2.7mm). The
      remaining 3 FS in 3 patients were artifacts; namely, residual blood and interface
      light reflectivity. There were no adverse cardiac events during 6-months follow
      up. CONCLUSIONS: In 5.1% of STEMI patients, post-procedural OFDI identified flaps
      with minimal involvement of the intima in the proximal coronary arteries. A
      precise interpretation of FS may help decision making to avoid unnecessary
      procedures. ( CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov
      identifier: NCT01271361.)

PMID- 23979570
TI  - High-throughput computer vision introduces the time axis to a quantitative trait
      map of a plant growth response.
AB  - Automated image acquisition, a custom analysis algorithm, and a distributed
      computing resource were used to add time as a third dimension to a quantitative
      trait locus (QTL) map for plant root gravitropism, a model growth response to an
      environmental cue. Digital images of Arabidopsis thaliana seedling roots from two
      independently reared sets of 162 recombinant inbred lines (RILs) and one set of
      92 near isogenic lines (NILs) derived from a Cape Verde Islands (Cvi) * Landsberg
      erecta (Ler) cross were collected automatically every 2 min for 8 hr following
      induction of gravitropism by 90 degrees  reorientation of the sample. High
      throughput computing (HTC) was used to measure root tip angle in each of the 1.1
      million images acquired and perform statistical regression of tip angle against
      the genotype at each of the 234 RIL or 102 NIL DNA markers independently at each
      time point using a standard stepwise procedure. Time-dependent QTL were detected
      on chromosomes 1, 3, and 4 by this mapping method and by an approach developed to
      treat the phenotype time course as a function-valued trait. The QTL on chromosome
      4 was earliest, appearing at 0.5 hr and remaining significant for 5 hr, while the
      QTL on chromosome 1 appeared at 3 hr and thereafter remained significant. The Cvi
      allele generally had a negative effect of 2.6-4.0%. Heritability due to the QTL
      approached 25%. This study shows how computer vision and statistical genetic
      analysis by HTC can characterize the developmental timing of genetic
      architectures. 

PMID- 23979571
TI  - Selecting informative traits for multivariate quantitative trait locus mapping
      helps to gain optimal power.
AB  - A major consideration in multitrait analysis is which traits should be jointly
      analyzed. As a common strategy, multitrait analysis is performed either on pairs
      of traits or on all of traits. To fully exploit the power of multitrait analysis,
      we propose variable selection to choose a subset of informative traits for
      multitrait quantitative trait locus (QTL) mapping. The proposed method is very
      useful for achieving optimal statistical power for QTL identification and for
      disclosing the most relevant traits. It is also a practical strategy to
      effectively take advantage of multitrait analysis when the number of traits under
      consideration is too large, making the usual multivariate analysis of all traits
      challenging. We study the impact of selection bias and the usage of permutation
      tests in the context of variable selection and develop a powerful implementation
      procedure of variable selection for genome scanning. We demonstrate the proposed
      method and selection procedure in a backcross population, using both simulated
      and real data. The extension to other experimental mapping populations is
      straightforward. 

PMID- 23979572
TI  - Rate of adaptation in sexuals and asexuals: a solvable model of the Fisher-Muller
      effect.
AB  - The adaptation of large asexual populations is hampered by the competition
      between independently arising beneficial mutations in different individuals,
      which is known as clonal interference. In classic work, Fisher and Muller
      proposed that recombination provides an evolutionary advantage in large
      populations by alleviating this competition. Based on recent progress in
      quantifying the speed of adaptation in asexual populations undergoing clonal
      interference, we present a detailed analysis of the Fisher-Muller mechanism for a
      model genome consisting of two loci with an infinite number of beneficial alleles
      each and multiplicative (nonepistatic) fitness effects. We solve the
      deterministic, infinite population dynamics exactly and show that, for a
      particular, natural mutation scheme, the speed of adaptation in sexuals is twice
      as large as in asexuals. This result is argued to hold for any nonzero value of
      the rate of recombination. Guided by the infinite population result and by
      previous work on asexual adaptation, we postulate an expression for the speed of
      adaptation in finite sexual populations that agrees with numerical simulations
      over a wide range of population sizes and recombination rates. The ratio of the
      sexual to asexual adaptation speed is a function of population size that
      increases in the clonal interference regime and approaches 2 for extremely large
      populations. The simulations also show that the imbalance between the numbers of
      accumulated mutations at the two loci is strongly suppressed even by a small
      amount of recombination. The generalization of the model to an arbitrary number L
      of loci is briefly discussed. If each offspring samples the alleles at each locus
      from the gene pool of the whole population rather than from two parents, the
      ratio of the sexual to asexual adaptation speed is approximately equal to L in
      large populations. A possible realization of this scenario is the reassortment of
      genetic material in RNA viruses with L genomic segments. 

PMID- 23979573
TI  - Population growth inflates the per-individual number of deleterious mutations and
      reduces their mean effect.
AB  - This study addresses the question of how purifying selection operates during
      recent rapid population growth such as has been experienced by human populations.
      This is not a straightforward problem because the human population is not at
      equilibrium: population genetics predicts that, on the one hand, the efficacy of
      natural selection increases as population size increases, eliminating ever more
      weakly deleterious variants; on the other hand, a larger number of deleterious
      mutations will be introduced into the population and will be more likely to
      increase in their number of copies as the population grows. To understand how
      patterns of human genetic variation have been shaped by the interaction of
      natural selection and population growth, we examined the trajectories of
      mutations with varying selection coefficients, using computer simulations. We
      observed that while population growth dramatically increases the number of
      deleterious segregating sites in the population, it only mildly increases the
      number carried by each individual. Our simulations also show an increased
      efficacy of natural selection, reflected in a higher fraction of deleterious
      mutations eliminated at each generation and a more efficient elimination of the
      most deleterious ones. As a consequence, while each individual carries a larger
      number of deleterious alleles than expected in the absence of growth, the average
      selection coefficient of each segregating allele is less deleterious. Combined,
      our results suggest that the genetic risk of complex diseases in growing
      populations might be distributed across a larger number of more weakly
      deleterious rare variants. 

PMID- 23979575
TI  - Genetic mapping and genomic selection using recombination breakpoint data.
AB  - The correct models for quantitative trait locus mapping are the ones that
      simultaneously include all significant genetic effects. Such models are difficult
      to handle for high marker density. Improving statistical methods for high
      dimensional data appears to have reached a plateau. Alternative approaches must
      be explored to break the bottleneck of genomic data analysis. The fact that all
      markers are located in a few chromosomes of the genome leads to linkage
      disequilibrium among markers. This suggests that dimension reduction can also be
      achieved through data manipulation. High-density markers are used to infer
      recombination breakpoints, which then facilitate construction of bins. The bins
      are treated as new synthetic markers. The number of bins is always a manageable
      number, on the order of a few thousand. Using the bin data of a recombinant
      inbred line population of rice, we demonstrated genetic mapping, using all bins
      in a simultaneous manner. To facilitate genomic selection, we developed a method
      to create user-defined (artificial) bins, in which breakpoints are allowed within
      bins. Using eight traits of rice, we showed that artificial bin data analysis
      often improves the predictability compared with natural bin data analysis. Of the
      eight traits, three showed high predictability, two had intermediate
      predictability, and two had low predictability. A binary trait with a known gene
      had predictability near perfect. Genetic mapping using bin data points to a new
      direction of genomic data analysis. 

PMID- 23979574
TI  - Nutritional control of epigenetic processes in yeast and human cells.
AB  - The vitamin folate is required for methionine homeostasis in all organisms. In
      addition to its role in protein synthesis, methionine is the precursor to S
      adenosyl-methionine (SAM), which is used in myriad cellular methylation
      reactions, including all histone methylation reactions. Here, we demonstrate that
      folate and methionine deficiency led to reduced methylation of lysine 4 of
      histone H3 (H3K4) in Saccharomyces cerevisiae. The effect of nutritional
      deficiency on H3K79 methylation was less pronounced, but was exacerbated in S.
      cerevisiae carrying a hypomorphic allele of Dot1, the enzyme responsible for
      H3K79 methylation. This result suggested a hierarchy of epigenetic modifications
      in terms of their susceptibility to nutritional limitations. Folate deficiency
      caused changes in gene transcription that mirrored the effect of complete loss of
      H3K4 methylation. Histone methylation was also found to respond to nutritional
      deficiency in the fission yeast Schizosaccharomyces pombe and in human cells in
      culture. 

PMID- 23979576
TI  - Heritable gene knockout in Caenorhabditis elegans by direct injection of Cas9
      sgRNA ribonucleoproteins.
AB  - We present a novel method of targeted gene disruption that involves direct
      injection of recombinant Cas9 protein complexed with guide RNA into the gonad of
      the nematode Caenorhabditis elegans. Biallelic mutants were recovered among the
      F1 progeny, demonstrating the high efficiency of this method. 

PMID- 23979577
TI  - Transgene-free genome editing in Caenorhabditis elegans using CRISPR-Cas.
AB  - CRISPR-Cas is an efficient method for genome editing in organisms from bacteria
      to human cells. We describe a transgene-free method for CRISPR-Cas-mediated
      cleavage in nematodes, enabling RNA-homology-targeted deletions that cause loss
      of gene function; analysis of whole-genome sequencing indicates that the nuclease
      activity is highly specific. 

PMID- 23979578
TI  - Targeted heritable mutation and gene conversion by Cas9-CRISPR in Caenorhabditis
      elegans.
AB  - We have achieved targeted heritable genome modification in Caenorhabditis elegans
      by injecting mRNA of the nuclease Cas9 and Cas9 guide RNAs. This system rapidly
      creates precise genomic changes, including knockouts and transgene-instructed
      gene conversion. 

PMID- 23979579
TI  - Heritable custom genomic modifications in Caenorhabditis elegans via a CRISPR
      Cas9 system.
AB  - We adapted the CRISPR-Cas9 system for template-mediated repair of targeted double
      strand breaks via homologous recombination in Caenorhabditis elegans, enabling
      customized and efficient genome editing. This system can be used to create
      specific insertions, deletions, and base pair changes in the germline of C.
      elegans. 

PMID- 23979580
TI  - Is the fungus Magnaporthe losing DNA methylation?
AB  - The long terminal repeat retrotransposon, Magnaporthe gypsy-like element (MAGGY),
      has been shown to be targeted for cytosine methylation in a subset of Magnaporthe
      oryzae field isolates. Analysis of the F1 progeny from a genetic cross between
      methylation-proficient (Br48) and methylation-deficient (GFSI1-7-2) isolates
      revealed that methylation of the MAGGY element was governed by a single dominant
      gene. Positional cloning followed by gene disruption and complementation
      experiments revealed that the responsible gene was the DNA methyltransferase,
      MoDMT1, an ortholog of Neurospora crassa Dim-2. A survey of MAGGY methylation in
      60 Magnaporthe field isolates revealed that 42 isolates from rice, common millet,
      wheat, finger millet, and buffelgrass were methylation proficient while 18
      isolates from foxtail millet, green bristlegrass, Japanese panicgrass, torpedo
      grass, Guinea grass, and crabgrass were methylation deficient. Phenotypic
      analyses showed that MoDMT1 plays no major role in development and pathogenicity
      of the fungus. Quantitative polymerase chain reaction analysis showed that the
      average copy number of genomic MAGGY elements was not significantly different
      between methylation-deficient and -proficient field isolates even though the
      levels of MAGGY transcript were generally higher in the former group. MoDMT1 gene
      sequences in the methylation-deficient isolates suggested that at least three
      independent mutations were responsible for the loss of MoDMT1 function. Overall,
      our data suggest that MoDMT1 is not essential for the natural life cycle of the
      fungus and raise the possibility that the genus Magnaporthe may be losing the
      mechanism of DNA methylation on the evolutionary time scale. 

PMID- 23979581
TI  - Complex genetic effects on early vegetative development shape resource allocation
      differences between Arabidopsis lyrata populations.
AB  - Costs of reproduction due to resource allocation trade-offs have long been
      recognized as key forces in life history evolution, but little is known about
      their functional or genetic basis. Arabidopsis lyrata, a perennial relative of
      the annual model plant A. thaliana with a wide climatic distribution, has
      populations that are strongly diverged in resource allocation. In this study, we
      evaluated the genetic and functional basis for variation in resource allocation
      in a reciprocal transplant experiment, using four A. lyrata populations and F2
      progeny from a cross between North Carolina (NC) and Norway parents, which had
      the most divergent resource allocation patterns. Local alleles at quantitative
      trait loci (QTL) at a North Carolina field site increased reproductive output
      while reducing vegetative growth. These QTL had little overlap with flowering
      date QTL. Structural equation models incorporating QTL genotypes and traits
      indicated that resource allocation differences result primarily from QTL effects
      on early vegetative growth patterns, with cascading effects on later vegetative
      and reproductive development. At a Norway field site, North Carolina alleles at
      some of the same QTL regions reduced survival and reproductive output components,
      but these effects were not associated with resource allocation trade-offs in the
      Norway environment. Our results indicate that resource allocation in perennial
      plants may involve important adaptive mechanisms largely independent of flowering
      time. Moreover, the contributions of resource allocation QTL to local adaptation
      appear to result from their effects on developmental timing and its interaction
      with environmental constraints, and not from simple models of reproductive costs.

PMID- 23979582
TI  - Mechanisms of ephrin receptor protein kinase-independent signaling in amphid axon
      guidance in Caenorhabditis elegans.
AB  - Eph receptors and their ephrin ligands are key conserved regulators of axon
      guidance and can function in a variety of signaling modes. Here we analyze the
      genetic and cellular requirements for Eph signaling in a Caenorhabditis elegans
      axon guidance choice point, the ventral guidance of axons in the amphid
      commissure. The C. elegans Eph receptor EFN-1 has both kinase-dependent and
      kinase-independent roles in amphid ventral guidance. Of the four C. elegans
      ephrins, we find that only EFN-1 has a major role in amphid axon ventral
      guidance, and signals in both a receptor kinase-dependent and kinase-independent
      manner. Analysis of EFN-1 and EFN-1 expression and tissue-specific requirements
      is consistent with a model in which VAB-1 acts in amphid neurons, interacting
      with EFN-1 expressed on surrounding cells. Unexpectedly, left-hand neurons are
      more strongly affected than right-hand neurons by loss of Eph signaling,
      indicating a previously undetected left-right asymmetry in the requirement for
      Eph signaling. By screening candidate genes involved in Eph signaling, we find
      that the Eph kinase-independent pathway involves the ABL-1 nonreceptor tyrosine
      kinase and possibly the phosphatidylinositol 3-kinase pathway. Overexpression of
      ABL-1 is sufficient to rescue EFN-1 ventral guidance defects cell autonomously.
      Our results reveal new aspects of Eph signaling in a single axon guidance
      decision in vivo. 

PMID- 23979583
TI  - Identification of Mob2, a novel regulator of larval neuromuscular junction
      morphology, in natural populations of Drosophila melanogaster.
AB  - Although evolutionary changes must take place in neural connectivity and synaptic
      architecture as nervous systems become more complex, we lack understanding of the
      general principles and specific mechanisms by which these changes occur.
      Previously, we found that morphology of the larval neuromuscular junction (NMJ)
      varies extensively among different species of Drosophila but is relatively
      conserved within a species. To identify specific genes as candidates that might
      underlie phenotypic differences in NMJ morphology among Drosophila species, we
      performed a genetic analysis on one of two phenotypic variants we found among 20
      natural isolates of Drosophila melanogaster. We discovered genetic polymorphisms
      for both positive and negative regulators of NMJ growth segregating within the
      variant line. Focusing on one subline, that displayed NMJ overgrowth, we mapped
      the phenotype to Mob2 [Monopolar spindle (Mps) one binding protein 2)], a gene
      encoding a Nuclear Dbf2 (Dumbbell formation 2)-Related (NDR) kinase activator. We
      confirmed this identification by transformation rescue experiments and showed
      that presynaptic expression of Mob2 is necessary and sufficient to regulate NMJ
      growth. Mob2 interacts in a dominant, dose-dependent manner with tricornered but
      not with warts, to cause NMJ overgrowth, suggesting that Mob2 specifically
      functions in combination with the former NDR kinase to regulate NMJ development.
      These results demonstrate the feasibility and utility of identifying genetic
      variants affecting NMJ morphology in natural populations of Drosophila. These
      variants can lead to discovery of new genes and molecular mechanisms that
      regulate NMJ development while also providing new information that can advance
      our understanding of mechanisms that underlie nervous system evolution. 

PMID- 23979584
TI  - Quantifying population genetic differentiation from next-generation sequencing
      data.
AB  - Over the past few years, new high-throughput DNA sequencing technologies have
      dramatically increased speed and reduced sequencing costs. However, the use of
      these sequencing technologies is often challenged by errors and biases associated
      with the bioinformatical methods used for analyzing the data. In particular, the
      use of naive methods to identify polymorphic sites and infer genotypes can
      inflate downstream analyses. Recently, explicit modeling of genotype probability
      distributions has been proposed as a method for taking genotype call uncertainty
      into account. Based on this idea, we propose a novel method for quantifying
      population genetic differentiation from next-generation sequencing data. In
      addition, we present a strategy for investigating population structure via
      principal components analysis. Through extensive simulations, we compare the new
      method herein proposed to approaches based on genotype calling and demonstrate a
      marked improvement in estimation accuracy for a wide range of conditions. We
      apply the method to a large-scale genomic data set of domesticated and wild
      silkworms sequenced at low coverage. We find that we can infer the fine-scale
      genetic structure of the sampled individuals, suggesting that employing this new
      method is useful for investigating the genetic relationships of populations
      sampled at low coverage. 

PMID- 23979585
TI  - Highly efficient targeted mutagenesis in mice using TALENs.
AB  - Targeted mouse mutants are instrumental for the analysis of gene function in
      health and disease. We recently provided proof-of-principle for the fast-track
      mutagenesis of the mouse genome, using transcription activator-like effector
      nucleases (TALENs) in one-cell embryos. Here we report a routine procedure for
      the efficient production of disease-related knockin and knockout mutants, using
      improved TALEN mRNAs that include a plasmid-coded poly(A) tail (TALEN-95A),
      circumventing the problematic in vitro polyadenylation step. To knock out the
      C9orf72 gene as a model of frontotemporal lobar degeneration, TALEN-95A
      mutagenesis induced sequence deletions in 41% of pups derived from microinjected
      embryos. Using TALENs together with mutagenic oligodeoxynucleotides, we
      introduced amyotrophic lateral sclerosis patient-derived missense mutations in
      the fused in sarcoma (Fus) gene at a rate of 6.8%. For the simple identification
      of TALEN-induced mutants and their progeny we validate high-resolution melt
      analysis (HRMA) of PCR products as a sensitive and universal genotyping tool.
      Furthermore, HRMA of off-target sites in mutant founder mice revealed no evidence
      for undesired TALEN-mediated processing of related genomic sequences. The
      combination of TALEN-95A mRNAs for enhanced mutagenesis and of HRMA for
      simplified genotyping enables the accelerated, routine production of new mouse
      models for the study of genetic disease mechanisms. 

PMID- 23979586
TI  - CRISPR/Cas9-targeted mutagenesis in Caenorhabditis elegans.
AB  - The generation of genetic mutants in Caenorhabditis elegans has long relied on
      the selection of mutations in large-scale screens. Directed mutagenesis of
      specific loci in the genome would greatly speed up analysis of gene function.
      Here, we adapt the CRISPR/Cas9 system to generate mutations at specific sites in
      the C. elegans genome. 

PMID- 23979588
TI  - Size-controlled photochemical synthesis of niobium nanoparticles.
AB  - The size of photochemically-prepared niobium nanoparticles (NbNP) can be
      controlled by varying the concentration of the photoinitiator in the reaction
      mixture. The particles, which may be metallic in nature, are readily oxidized
      upon air exposure to form stable niobium(v) oxide nanoparticles (NbONP) that act
      as strong Bronsted acids. 

PMID- 23979589
TI  - Osteoarthritis: positive feedback between ADAMTS-7 and TNF in OA.

PMID- 23979587
TI  - Coordination and processing of DNA ends during double-strand break repair: the
      role of the bacteriophage T4 Mre11/Rad50 (MR) complex.
AB  - The in vivo functions of the bacteriophage T4 Mre11/Rad50 (MR) complex (gp46/47)
      in double-strand-end processing, double-strand break repair, and recombination
      dependent replication were investigated. The complex is essential for T4 growth,
      but we wanted to investigate the in vivo function during productive infections.
      We therefore generated a suppressed triple amber mutant in the Rad50 subunit to
      substantially reduce the level of complex and thereby reduce phage growth. Growth
      limiting amounts of the complex caused a concordant decrease in phage genomic
      recombination-dependent replication. However, the efficiencies of double-strand
      break repair and of plasmid-based recombination-dependent replication remained
      relatively normal. Genetic analyses of linked markers indicated that double
      strand ends were less protected from nuclease erosion in the depleted infection
      and also that end coordination during repair was compromised. We discuss models
      for why phage genomic recombination-dependent replication is more dependent on
      Mre11/Rad50 levels when compared to plasmid recombination-dependent replication.
      We also tested the importance of the conserved histidine residue in nuclease
      motif I of the T4 Mre11 protein. Substitution with multiple different amino acids
      (including serine) failed to support phage growth, completely blocked plasmid
      recombination-dependent replication, and led to the stabilization of double
      strand ends. We also constructed and expressed an Mre11 mutant protein with the
      conserved histidine changed to serine. The mutant protein was found to be
      completely defective for nuclease activities, but retained the ability to bind
      the Rad50 subunit and double-stranded DNA. These results indicate that the
      nuclease activity of Mre11 is critical for phage growth and recombination
      dependent replication during T4 infections. 

PMID- 23979590
TI  - A trade based view on casino taxation: market conditions.
AB  - This article presents a trade based theory of casino taxation along with
      empirical evidence found from Macao as a typical tourism resort. We prove that
      there is a unique optimum gaming tax in a particular market for casino gambling,
      argue that any change in this tax is engendered by external demand shifts, and
      suggest that the economic rent from gambling legalization should be shared
      through such optimal tax between the public and private sectors. Our work also
      studies the tradeoff between economic benefits and social costs arising from
      casino tourism, and provides some policy recommendations for the sustainable
      development of gaming-led economies. The theoretical arguments in this article
      turn out to be consistent with empirical observations on Macao realities over the
      recent decade. 

PMID- 23979592
TI  - The heme a synthase Cox15 associates with cytochrome c oxidase assembly
      intermediates during Cox1 maturation.
AB  - Cox1, the core subunit of the cytochrome c oxidase, receives two heme a cofactors
      during assembly of the 13-subunit enzyme complex. However, at which step of the
      assembly process and how heme is inserted into Cox1 have remained an enigma.
      Shy1, the yeast SURF1 homolog, has been implicated in heme transfer to Cox1,
      whereas the heme a synthase, Cox15, catalyzes the final step of heme a synthesis.
      Here we performed a comprehensive analysis of cytochrome c oxidase assembly
      intermediates containing Shy1. Our analyses suggest that Cox15 displays a role in
      cytochrome c oxidase assembly, which is independent of its functions as the heme
      a synthase. Cox15 forms protein complexes with Shy1 and also associates with Cox1
      containing complexes independently of Shy1 function. These findings indicate that
      Shy1 does not serve as a mobile heme carrier between the heme a synthase and
      maturing Cox1 but rather cooperates with Cox15 for heme transfer and insertion in
      early assembly intermediates of cytochrome c oxidase. 

PMID- 23979591
TI  - Homodimerization of the Wnt receptor DERAILED recruits the Src family kinase
      SRC64B.
AB  - Ryk pseudokinase receptors act as important transducers of Wnt signals,
      particularly in the nervous system. Little is known, however, of their
      interactions at the cell surface. Here, we show that a Drosophila Ryk family
      member, DERAILED (DRL), forms cell surface homodimers and can also heterodimerize
      with the two other fly Ryks, DERAILED-2 and DOUGHNUT ON 2. DERAILED
      homodimerization levels increase significantly in the presence of its ligand,
      WNT5. In addition, DERAILED displays ligand-independent dimerization mediated by
      a motif in its transmembrane domain. Increased dimerization of DRL upon WNT5
      binding or upon the replacement of DERAILED's extracellular domain with the
      immunoglobulin Fc domain results in an increased recruitment of the Src family
      kinase SRC64B, a previously identified downstream pathway effector. Formation of
      the SRC64B/DERAILED complex requires SRC64B's SH2 domain and DERAILED's PDZ
      binding motif. Mutations in DERAILED's inactive tyrosine kinase-homologous domain
      also disrupt the formation of DERAILED/SRC64B complexes, indicating that its
      conformation is likely important in facilitating its interaction with SRC64B.
      Finally, we show that DERAILED's function during embryonic axon guidance requires
      its Wnt-binding domain, a putative juxtamembrane extracellular tetrabasic
      cleavage site, and the PDZ-binding domain, indicating that DERAILED's activation
      involves a complex set of events including both dimerization and proteolytic
      processing. 

PMID- 23979593
TI  - Mbd2 promotes foxp3 demethylation and T-regulatory-cell function.
AB  - Use of Foxp3-positive (Foxp3(+)) T-regulatory (Treg) cells as potential cellular
      therapy in patients with autoimmunity, or post-stem cell or -organ
      transplantation, requires a sound understanding of the transcriptional regulation
      of Foxp3. Conserved CpG dinucleotides in the Treg-specific demethylation region
      (TSDR) upstream of Foxp3 are demethylated only in stable, thymus-derived Foxp3(+)
      Treg cells. Since methyl-binding domain (Mbd) proteins recruit histone-modifying
      and chromatin-remodeling complexes to methylated sites, we tested whether
      targeting of Mbd2 might promote demethylation of Foxp3 and thereby promote Treg
      numbers or function. Surprisingly, while chromatin immunoprecipitation (ChIP)
      analysis showed Mbd2 binding to the Foxp3-associated TSDR site in Treg cells,
      Mbd2 targeting by homologous recombination, or small interfering RNA (siRNA),
      decreased Treg numbers and impaired Treg-suppressive function in vitro and in
      vivo. Moreover, we found complete TSDR demethylation in wild-type (WT) Treg cells
      but >75% methylation in Mbd2(-/-) Treg cells, whereas reintroduction of Mbd2 into
      Mbd2-null Treg cells restored TSDR demethylation, Foxp3 gene expression, and Treg
      suppressive function. Lastly, thymic Treg cells from Mbd2(-/-) mice had normal
      TSDR demethylation, but compared to WT Treg cells, peripheral Mbd2(-/-) Treg
      cells had a marked impairment of binding of Tet2, the DNA demethylase enzyme, at
      the TSDR site. These data show that Mbd2 has a key role in promoting TSDR
      demethylation, Foxp3 expression, and Treg-suppressive function. 

PMID- 23979594
TI  - Deletion of Cdc42 enhances ADAM17-mediated vascular endothelial growth factor
      receptor 2 shedding and impairs vascular endothelial cell survival and
      vasculogenesis.
AB  - Cdc42 is a Ras-related GTPase that plays an important role in the regulation of a
      range of cellular functions, including cell migration, proliferation, and
      survival. Consistent with its critical functions in vitro, the inactivation of
      Cdc42 in mice has been shown to result in embryonic lethality at embryonic day
      6.5 (E6.5) before blood vessel formation. To determine the role of Cdc42 in new
      blood vessel formation, we have generated vascular endothelial cell (EC)-specific
      Cdc42 knockout mice by crossing Cdc42(flox/flox) mice with Tie2-Cre mice. The
      deletion of Cdc42 in ECs caused embryonic lethality with vasculogenesis and
      angiogenesis defects. We observed that Cdc42 is critical for EC migration and
      survival but not for cell cycle progression. Moreover, we found that the
      inactivation of Cdc42 in ECs decreased the level of vascular endothelial growth
      factor receptor 2 (VEGFR2) protein on the EC surface and promoted the production
      of a 75-kDa membrane-associated C-terminal VEGFR2 fragment. Using cultured
      primary mouse ECs and human umbilical vein ECs, we have demonstrated that the
      deletion of Cdc42 increased ADAM17-mediated VEGFR2 shedding. Notably, inhibition
      of ADAM17 or overexpression of VEGFR2 can partially reverse Cdc42 deletion
      induced EC apoptosis. These data indicate that Cdc42 is essential for VEGFR2
      mediated signal transduction in blood vessel formation. 

PMID- 23979595
TI  - Histone methylation keeps the brakes on autophagy.

PMID- 23979596
TI  - Multipoint binding of the SLP-76 SH2 domain to ADAP is critical for
      oligomerization of SLP-76 signaling complexes in stimulated T cells.
AB  - The adapter molecules SLP-76 and LAT play central roles in T cell activation by
      recruiting enzymes and other adapters into multiprotein complexes that coordinate
      highly regulated signal transduction pathways. While many of the associated
      proteins have been characterized, less is known concerning the mechanisms of
      assembly for these dynamic and potentially heterogeneous signaling complexes.
      Following T cell receptor (TCR) stimulation, SLP-76 is found in structures called
      microclusters, which contain many signaling complexes. Previous studies showed
      that a mutation to the SLP-76 C-terminal SH2 domain nearly abolished SLP-76
      microclusters, suggesting that the SH2 domain facilitates incorporation of
      signaling complexes into microclusters. S. C. Bunnell, A. L. Singer, D. I. Hong,
      B. H. Jacque, M. S. Jordan, M. C. Seminario, V. A. Barr, G. A. Koretzky, and L.
      E. Samelson, Mol. Cell. Biol., 26:7155-7166, 2006). Using biophysical methods, we
      demonstrate that the adapter, ADAP, contains three binding sites for SLP-76, and
      that multipoint binding to ADAP fragments oligomerizes the SLP-76 SH2 domain in
      vitro. These results were complemented with confocal imaging and functional
      studies of cells expressing ADAP with various mutations. Our results demonstrate
      that all three binding sites are critical for SLP-76 microcluster assembly, but
      any combination of two sites will partially induce microclusters. These data
      support a model whereby multipoint binding of SLP-76 to ADAP facilitates the
      assembly of SLP-76 microclusters. This model has implications for the regulation
      of SLP-76 and LAT microclusters and, as a result, T cell signaling. 

PMID- 23979597
TI  - The G2/M regulator histone demethylase PHF8 is targeted for degradation by the
      anaphase-promoting complex containing CDC20.
AB  - Monomethylated histone H4 lysine 20 (H4K20me1) is tightly regulated during the
      cell cycle. The H4K20me1 demethylase PHF8 transcriptionally regulates many cell
      cycle genes and is therefore predicted to play key roles in the cell cycle. Here,
      we show that PHF8 protein levels are the highest during G2 phase and mitosis, and
      we found PHF8 protein stability to be regulated by the ubiquitin-proteasome
      system. Purification of the PHF8 complex led to the identification of many
      subunits of the anaphase-promoting complex (APC) associated with PHF8. We showed
      that PHF8 interacts with the CDC20-containing APC (APC(cdc20)) primarily during
      mitosis. In addition, we defined a novel, KEN- and D-box-independent, LXPKXLF
      motif on PHF8 that is required for binding to CDC20. Through various in vivo and
      in vitro assays, we demonstrate that mutations of the LXPKXLF motif abrogate
      polyubiquitylation of PHF8 by the APC. APC substrates are typically cell cycle
      regulators, and consistent with this, the loss of PHF8 leads to prolonged G2
      phase and defective mitosis. Furthermore, we provide evidence that PHF8 plays an
      important role in transcriptional activation of key G2/M genes during G2 phase.
      Taken together, these findings suggest that PHF8 is regulated by APC(cdc20) and
      plays an important role in the G2/M transition.

PMID- 23979598
TI  - Casein kinase 2 associates with the yeast chromatin reassembly factor Spt2/Sin1
      to regulate its function in the repression of spurious transcription.
AB  - Spt2/Sin1 is a DNA binding protein with HMG-like domains. It plays a role in
      chromatin modulations associated with transcription elongation in Saccharomyces
      cerevisiae. Spt2 maintains the nucleosome level in coding regions and is
      important for the inhibition of spurious transcription in yeast. In this work, we
      undertook a biochemical approach to identify Spt2-interacting partners.
      Interestingly, casein kinase 2 (CK2) interacts with Spt2 and phosphorylates it in
      vitro as well as in vivo on two small regions, region I (RI) (amino acids 226 to
      230) and RII (amino acids 277 to 281), located in its essential C-terminal
      domain. Mutation of the phosphorylation sites in RI and RII to acidic residues,
      thereby mimicking CK2 phosphorylation, leads to the inhibition of Spt2 function
      in the repression of spurious transcription and to a loss of its recruitment to
      coding regions. Inversely, depleting cells of CK2 activity leads to an increased
      Spt2 association with genes. We further show that Spt2 physically interacts with
      the essential histone chaperone Spt6 and that this association is inhibited in
      vitro and in vivo by CK2-dependent phosphorylation. Taken together, our data
      suggest that CK2 regulates the function of Spt2 by modulating its interaction
      with chromatin and the histone chaperone Spt6. 

PMID- 23979599
TI  - Cyp1b1 mediates periostin regulation of trabecular meshwork development by
      suppression of oxidative stress.
AB  - Mutation in CYP1B1 has been reported for patients with congenital glaucoma.
      However, the underlying mechanisms remain unknown. Here we show increased diurnal
      intraocular pressure (IOP) in Cyp1b1-deficient (Cyp1b1(-/-)) mice. Cyp1b1(-/-)
      mice presented ultrastructural irregular collagen distribution in their
      trabecular meshwork (TM) tissue along with increased oxidative stress and
      decreased levels of periostin (Postn). Increased levels of oxidative stress and
      decreased levels of Postn were also detected in human glaucomatous TM tissues.
      Furthermore, Postn-deficient mice exhibited TM tissue ultrastructural
      abnormalities similar to those of Cyp1b1(-/-) mice. Administration of the
      antioxidant N-acetylcysteine (NAC) restored structural abnormality of TM tissue
      in Cyp1b1(-/-) mice. In addition, TM cells prepared from Cyp1b1(-/-) mice
      exhibited increased oxidative stress, altered adhesion, and decreased levels of
      Postn. These aberrant cellular responses were reversed in the presence of NAC or
      by restoration of Cyp1b1 expression. Cyp1b1 knockdown or inhibition of CYP1B1
      activity in Cyp1b1(+/+) TM cells resulted in a Cyp1b1(-/-) phenotype. Thus,
      metabolic activity of CYP1B1 contributes to oxidative homeostasis and
      ultrastructural organization and function of TM tissue through modulation of
      Postn expression. 

PMID- 23979600
TI  - Deacetylase Rpd3 facilitates checkpoint adaptation by preventing Rad53
      overactivation.
AB  - The DNA damage checkpoint is tightly controlled. After its activation, the
      checkpoint machinery is inactivated once lesions are repaired or undergoes
      adaptation if the DNA damage is unable to be repaired. Protein acetylation has
      been shown to play an important role in DNA damage checkpoint activation.
      However, the role of acetylation in checkpoint inactivation is unclear. Here we
      show that histone deacetylase Rpd3-mediated deacetylation of Rad53 plays an
      important role in checkpoint adaptation. Deletion of Rpd3 or inhibition of its
      activity impairs adaptation. RPD3 deletion also leads to a higher acetylation
      level and enhanced kinase activity of Rad53. Replacement of two major acetylation
      sites of Rad53 with arginine reduces its activity and further suppresses the
      adaptation defect of rpd3Delta cells, indicating that Rpd3 facilitates adaptation
      by preventing Rad53 overactivation. Similar to its role in adaptation, deletion
      of RPD3 or inhibition of its activity also suppressed checkpoint recovery.
      Altogether, our findings reveal an important role of Rpd3 in promoting checkpoint
      adaptation via deacetylation and inhibition of Rad53. 

PMID- 23979601
TI  - Cross talk between the Akt and p38alpha pathways in macrophages downstream of
      Toll-like receptor signaling.
AB  - The stimulation of Toll-like receptors (TLRs) on macrophages by pathogen
      associated molecular patterns (PAMPs) results in the activation of intracellular
      signaling pathways that are required for initiating a host immune response. Both
      phosphatidylinositol 3-kinase (PI3K)-Akt and p38 mitogen-activated protein kinase
      (MAPK) signaling pathways are activated rapidly in response to TLR activation and
      are required to coordinate effective host responses to pathogen invasion. In this
      study, we analyzed the role of the p38-dependent kinases MK2/3 in the activation
      of Akt and show that lipopolysaccharide (LPS)-induced phosphorylation of Akt on
      Thr308 and Ser473 requires p38alpha and MK2/3. In cells treated with p38
      inhibitors or an MK2/3 inhibitor, phosphorylation of Akt on Ser473 and Thr308 is
      reduced and Akt activity is inhibited. Furthermore, BMDMs deficient in MK2/3
      display greatly reduced phosphorylation of Ser473 and Thr308 following TLR
      stimulation. However, MK2/3 do not directly phosphorylate Akt in macrophages but
      act upstream of PDK1 and mTORC2 to regulate Akt phosphorylation. Akt is recruited
      to phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the membrane, where it is
      activated by PDK1 and mTORC2. Analysis of lipid levels in MK2/3-deficient bone
      marrow-derived macrophages (BMDMs) revealed a role for MK2/3 in regulating Akt
      activity by affecting availability of PIP3 at the membrane. These data describe a
      novel role for p38alpha-MK2/3 in regulating TLR-induced Akt activation in
      macrophages. 

PMID- 23979603
TI  - Exposure to cadmium from food and risk of cardiovascular disease in men: a
      population-based prospective cohort study.

PMID- 23979602
TI  - Genome-wide investigation of the role of the tRNA nuclear-cytoplasmic trafficking
      pathway in regulation of the yeast Saccharomyces cerevisiae transcriptome and
      proteome.
AB  - In eukaryotic cells, tRNAs are transcribed and partially processed in the nucleus
      before they are exported to the cytoplasm, where they have an essential role in
      protein synthesis. Surprisingly, mature cytoplasmic tRNAs shuttle between nucleus
      and cytoplasm, and tRNA subcellular distribution is nutrient dependent. At least
      three members of the beta-importin family, Los1, Mtr10, and Msn5, function in
      tRNA nuclear-cytoplasmic intracellular movement. To test the hypothesis that the
      tRNA retrograde pathway regulates the translation of particular transcripts, we
      compared the expression profiles from nontranslating mRNAs and polyribosome
      associated translating mRNAs collected from msn5Delta, mtr10Delta, and wild-type
      cells under fed or acute amino acid depletion conditions. Our microarray data
      revealed that the methionine, arginine, and leucine biosynthesis pathways are
      targets of the tRNA retrograde process. We confirmed the microarray data by
      Northern and Western blot analyses. The levels of some of the particular target
      mRNAs were reduced, while others appeared not to be affected. However, the
      protein levels of all tested targets in these pathways were greatly decreased
      when tRNA nuclear import or reexport to the cytoplasm was disrupted. This study
      provides information that tRNA nuclear-cytoplasmic dynamics is connected to the
      biogenesis of proteins involved in amino acid biosynthesis. 

PMID- 23979604
TI  - A rare mutation of CACNA1C in a patient with bipolar disorder, and decreased gene
      expression associated with a bipolar-associated common SNP of CACNA1C in brain.
AB  - Timothy Syndrome (TS) is caused by very rare exonic mutations of the CACNA1C gene
      that produce delayed inactivation of Cav1.2 voltage-gated calcium channels during
      cellular action potentials, with greatly increased influx of calcium into the
      activated cells. The major clinical feature of this syndrome is a long QT
      interval that results in cardiac arrhythmias. However, TS also includes cognitive
      impairment, autism and major developmental delays in many of the patients. We
      observed the appearance of bipolar disorder (BD) in a patient with a previously
      reported case of TS, who is one of the very few patients to survive childhood.
      This is most interesting because the common single-nucleotide polymorphism (SNP)
      most highly associated with BD is rs1006737, which we show here is a cis
      expression quantitative trait locus for CACNA1C in human cerebellum, and the risk
      allele (A) is associated with decreased expression. To combine the CACNA1C
      perturbations in the presence of BD in this patient and in patients with the
      common CACNA1C SNP risk allele, we would propose that either increase or decrease
      in calcium influx in excitable cells can be associated with BD. In treatment of
      BD with calcium channel blocking drugs, we would predict better response in
      patients without the risk allele, because they have increased CACNA1C expression.

PMID- 23979606
TI  - Hippocampal interneuron transplants reverse aberrant dopamine system function and
      behavior in a rodent model of schizophrenia.
AB  - Schizophrenia patients exhibit increased hippocampal activity that is correlated
      with positive symptoms. Although the cause of this hippocampal hyperactivity has
      not been demonstrated, it likely involves a decrease in GABAergic signaling.
      Thus, we posit that restoring GABAergic function may provide a novel therapeutic
      approach for the treatment of schizophrenia. It has been demonstrated that
      transplanted GABAergic precursor cells from the medial ganglionic eminence (MGE)
      can migrate and differentiate into mature interneurons. Here, we demonstrate that
      ventral hippocampal MGE transplants can restore hippocampal function and
      normalize downstream dopamine neuron activity in a rodent model of schizophrenia.
      Furthermore, MGE transplants also reverse the hyper-responsive locomotor response
      to amphetamine. Taken together, these data demonstrate that restoring interneuron
      function reverses neurophysiological and behavioral deficits in a rodent model of
      schizophrenia and moreover, demonstrate the feasibility of a neuronal transplant
      procedure as a potential novel therapeutic approach for the treatment of
      schizophrenia. 

PMID- 23979605
TI  - De novo mutation in the dopamine transporter gene associates dopamine dysfunction
      with autism spectrum disorder.
AB  - De novo genetic variation is an important class of risk factors for autism
      spectrum disorder (ASD). Recently, whole-exome sequencing of ASD families has
      identified a novel de novo missense mutation in the human dopamine (DA)
      transporter (hDAT) gene, which results in a Thr to Met substitution at site 356
      (hDAT T356M). The dopamine transporter (DAT) is a presynaptic membrane protein
      that regulates dopaminergic tone in the central nervous system by mediating the
      high-affinity reuptake of synaptically released DA, making it a crucial regulator
      of DA homeostasis. Here, we report the first functional, structural and
      behavioral characterization of an ASD-associated de novo mutation in the hDAT. We
      demonstrate that the hDAT T356M displays anomalous function, characterized as a
      persistent reverse transport of DA (substrate efflux). Importantly, in the
      bacterial homolog leucine transporter, substitution of A289 (the homologous site
      to T356) with a Met promotes an outward-facing conformation upon substrate
      binding. In the substrate-bound state, an outward-facing transporter conformation
      is required for substrate efflux. In Drosophila melanogaster, the expression of
      hDAT T356M in DA neurons-lacking Drosophila DAT leads to hyperlocomotion, a trait
      associated with DA dysfunction and ASD. Taken together, our findings demonstrate
      that alterations in DA homeostasis, mediated by aberrant DAT function, may confer
      risk for ASD and related neuropsychiatric conditions. 

PMID- 23979607
TI  - Genome-wide analyses of borderline personality features.
AB  - The heritability of borderline personality (BP) features has been established in
      multiple twin and family studies. Using data from the borderline subscale of the
      Personality Assessment Inventory Borderline Features Scale (PAI-BOR) collected in
      two Dutch cohorts (N=7125), the Netherlands Twin Register and The Netherlands
      Study of Depression and Anxiety, we show that heritability of the PAI-BOR total
      score using genome-wide single-nucleotide polymorphism (SNPs) is estimated at
      23%, and that the genetic variance is substantially higher in affect instability
      items compared with the other three subscales of the PAI-BOR (42.7% vs non
      significant estimates for self-harm, negative relations and identity problems).
      We present results from a first genome-wide association study of BP features,
      which shows a promising signal on chromosome 5 corresponding to SERINC5, a
      protein involved in myelination. Reduced myelination has been suggested as
      possibly having a role in the development of psychiatric disorders characterized
      by lack of social interaction. The signal was confirmed in a third independent
      Dutch cohort drawn from the Erasmus Rucphen Family study (N=1301). Our analyses
      were complemented by investigating the heterogeneity that was implied by the
      differences in genetic variance components in the four subscales of the PAI-BOR.
      These analyses show that the association of SNPs tagging SERINC5 differs
      substantially across the 24 items of the PAI-BOR. Further, using reverse
      regression we showed that the effects were present only in subjects with higher
      scores on the PAI-BOR. Taken together, these results suggest that future genome
      wide analyses can benefit substantially by taking into account the phenotypic and
      genetic heterogeneity of BP features. 

PMID- 23979610
TI  - The meaning of clinical ultrasound: clinical ultrasound and guidelines.

PMID- 23979608
TI  - GCPII modulates oxidative stress and prostate cancer susceptibility through
      changes in methylation of RASSF1, BNIP3, GSTP1 and Ec-SOD.
AB  - Glutamate carboxypeptidase II (GCPII) haplotypes were found to influence
      susceptibility to prostate cancer. In the current study, we have elucidated the
      impact of these haplotypes on the expression of PSMA, BNIP3, Ec-SOD, GSTP1 and
      RASSF1 genes to understand the epigenetic basis of oxidative stress and prostate
      cancer risk. Expression analysis was carried out by RT-PCR. Bisulphite treated
      DNA was subjected to MS-PCR and COBRA for epigenetic studies. Plasma MDA and
      glutathione levels were measured. In prostate cancer, upregulation of BNIP3
      (204.4 +/- 23.77 vs. 143.9 +/- 16.42 %, p = 0.03); and downregulation of Ec-SOD
      (105.8 +/- 13.69 vs. 176.3 +/- 21.1 %, p = 0.027) and RASSF1A (16.67 +/- 16.0 vs.
      90.8 +/- 8.5 %, p = 0.0048) was observed. Hypomethylation of BNIP3 (31.25 +/-
      16.19 vs. 45.70 +/- 2.42 %, p < 0.0001), hypermethylation of Ec-SOD (71.4 +/-
      6.75 vs. 10.0 +/- 3.78 %, p < 0.0001) and RASSF1 (76.25 +/- 12.53 vs. 30.0 +/-
      8.82 %, p = 0.0077) was observed in prostate cancer. The gene expression
      signature of PSMA, BNIP3, Ec-SOD, GSTP1, clearly demarcated cases and controls
      (AUC = 0.89 in the ROC curve). D191V variant of GCPII showed positive association
      with oxidative stress and inverse association with Ec-SOD expression. H475Y
      variant showed positive association with Ec-SOD expression and inverse
      association with oxidative stress. R190W variant was found to reduce oxidative
      stress by increasing glutathione levels. GCPII genetic variants contribute to
      increased oxidative stress and prostate cancer risk by modulating the CpG island
      methylation of Ec-SOD.

PMID- 23979609
TI  - The contribution of de novo and rare inherited copy number changes to congenital
      heart disease in an unselected sample of children with conotruncal defects or
      hypoplastic left heart disease.
AB  - Congenital heart disease (CHD) is the most common congenital malformation, with
      evidence of a strong genetic component. We analyzed data from 223 consecutively
      ascertained families, each consisting of at least one child affected by a
      conotruncal defect (CNT) or hypoplastic left heart disease (HLHS) and both
      parents. The NimbleGen HD2-2.1 comparative genomic hybridization platform was
      used to identify de novo and rare inherited copy number variants (CNVs).
      Excluding 10 cases with 22q11.2 DiGeorge deletions, we validated de novo CNVs in
      8 % of 148 probands with CNTs, 12.7 % of 71 probands with HLHS and none in 4
      probands with both. Only 2 % of control families showed a de novo CNV. We also
      identified a group of ultra-rare inherited CNVs that occurred de novo in our
      sample, contained a candidate gene for CHD, recurred in our sample or were
      present in an affected sibling. We confirmed the contribution to CHD of copy
      number changes in genes such as GATA4 and NODAL and identified several genes in
      novel recurrent CNVs that may point to novel CHD candidate loci. We also found
      CNVs previously associated with highly variable phenotypes and reduced
      penetrance, such as dup 1q21.1, dup 16p13.11, dup 15q11.2-13, dup 22q11.2, and
      del 2q23.1. We found that the presence of extra-cardiac anomalies was not related
      to the frequency of CNVs, and that there was no significant difference in CNV
      frequency or specificity between the probands with CNT and HLHS. In agreement
      with other series, we identified likely causal CNVs in 5.6 % of our total sample,
      half of which were de novo.

PMID- 23979611
TI  - ARFI quantitative elastography of the submandibular glands. Normal measurements
      and the diagnosis value of the method in radiation submaxillitis.
AB  - OBJECTIVES: Evaluation of Acoustic Radiation Force Impulse Imaging (ARFI)
      elastography performance in predicting the elasticity of the submandibular glands
      in normal situations and after radiation therapy. MATERIAL AND METHOD: A number
      of 54 normal submandibular glands from 27 voluntary subjects and 33 pathological
      submandibular glands (radiation submaxillities) from 18 patients who had
      undergone radiation therapy for various cervical and facial oncological
      conditions were included in study. All the patients had undergone a B mode
      ultrasonography (Tissue Harmonic Imaging, 8-14 MHz) while the submandibular
      volume was determined and subsequently an ARFI examination while the shear wave
      velocity (SWV) was measured (in the central, peripheral and subcapsular areas,
      with the results expressed in m/s). RESULTS: In the volunteers' group the mean
      value of the SWV of the left submandibular gland was 1.68 +/- 0.46 m/s,
      determined in the centre of the gland, 1.88 +/- 0.4 m/s in the periphery
      (corresponding to the subcapsular parenchyma) and the SWV of the right
      submandibular gland was 1.74 +/- 0.35 m/s (centrally) and 1.84 +/- 0.43 m/s in
      the periphery. The mean value of all measurements was 1.82 +/- 0.41 m/s. The mean
      volume of the glands was 7.97 +/- 2.63 cm3. In the group of patients who had
      underwent radiation therapy (at least 35Gy), the mean value of the SWV was 2.24
      +/- 0.49 m/s centrally and 2.1 +/- 0.58 m/s in the periphery on the left and 1.99
      +/- 0.5 m/s centrally and 2.21 +/- 0.52 m/s in the periphery on the right. The
      mean value of all the measurements was 2.13 +/- 0.52 m/s and the mean volume of
      the gland was 5.95 +/- 4.16 cm3. CONCLUSIONS: Elastography using ARFI technique
      is a valid examination in the evaluation of the normal and pathological
      submandibular gland stiffness. The values of the shear wave velocities that
      correspond to a normal stiffness, determined through the ARFI technique, are
      similar in the two glands. After cervical and facial radiation therapy the values
      of the SWV are increased, indicating a change in the consistency of the gland
      thus implying a structural transformation. The ARFI technique can be used in the
      evaluation of the salivary glands pathology.

PMID- 23979612
TI  - Does experience play a role in the ability to perform liver stiffness
      measurements by means of supersonic shear imaging (SSI)?
AB  - The aim of this study was to identify if the experience of the examiner does
      plays a role in the ability to perform liver stiffness (LS) measurements by means
      of supersonic shear imaging (SSI) due to the lack of recommendation regarding
      this issue. MATERIAL AND METHODS: The study included 371 consecutive subjects
      (42% men and 58% women, with a median age of 48 years, ranging between 17-85
      years) with or without hepatopathies, in which LS was evaluated with an
      AixplorerTM ultrasound system (SuperSonic Imagine S.A., Aix-en-Provence, France).
      Reliable LS measurements by means of SSI were defined as the median value of 5 LS
      measurements expressed in kilopascals (kPa). The SSI measurements were performed
      by a novice (with less than 300 abdominal ultrasound examinations performed) or
      by a more experienced operator (with approximately 500 ultrasound examinations
      performed). The results of both operators were compared. RESULTS: The novice
      performed 57.4% and the more experienced operator 42.6% of the SSI measurements.
      The more experienced operator had a higher rate of reliable examinations as
      compared with the novice: 87.4% vs. 72.8% (p =0.001). The rate of reliable
      measurements was similar for novice and experienced operator in patients with a
      normal weight (BMI < 25 kg/m2) and in overweight patients (BMI between 25.1 -
      29.9 kg/m2), 92.3% vs. 97.5%, p=0.24, respectively 71.1% vs 80.4%, p=0.39. For
      obese patients (BMI >= 30 kg/m2) the rate of reliable LS measurements was
      significantly higher for the more experienced operator as compared with the
      novice: 73.4% vs 45.9%, p=0.03. CONCLUSIONS: It seems that experience in liver
      ultrasonography plays a role in the ability to perform LS measurements by means
      of SSI and leads to achieving more reliable LS measurements especially in obese
      subjects.

PMID- 23979613
TI  - Computer aided diagnosis method for steatosis rating in ultrasound images using
      random forests.
AB  - In this paper we discuss the problem of computer aided evaluation of the severity
      of steatosis disease using ultrasound images. The AIM of the study being to
      compare the automatic evaluation of liver steatosis using random forests (RF) and
      support vector machine (SVM) classifiers. MATERIAL AND METHOD: One hundred and
      twenty consecutive patients with steatosis or normal liver, assessed by
      ultrasound by the same expert, were enrolled. We graded steatosis in four stages
      and trained two classifiers to rate the severity of disease, based on a large set
      of labeled images and a large set of features, including several features
      obtained by robust estimation techniques. We compared RF and SVM classifiers. The
      classifiers were trained using cross-validation. There was 80% of data randomly
      selected for training and 20% for testing the classifier. This procedure was
      performed 20 times. The main measure of performance was the accuracy. RESULTS:
      From all cases, 10 were rated as normal liver, 70 as having mild, 33 moderate,
      and 7 severe steatosis. Our best experts' ratings were used as ground truth data.
      RF outperformed the SVM classifier and confirmed the ability of this classifier
      to perform well without feature selection. In contrast, the performance of the
      SVM classifier was poor without feature selection and improved significantly
      after feature selection. CONCLUSION: The ability and accuracy of RF to classify
      well the steatosis severity, without feature selection, were superior as compared
      to SVM.

PMID- 23979614
TI  - Predicting factors on cervical ripening and response to induction in women
      pregnant over 37 weeks.
AB  - Induction of labor is conducted in special fetal or maternal conditions. Labor is
      induced in about 20% of women. The AIM of this study was realizing the
      relationship between some factors including cervical ripening and also response
      to induction so we could predict the induction outcome better. MATERIAL AND
      METHODS: The present prospective study was based on 101 pregnancy cases admitted
      to the labor ward in Urmia from March 2010 until December 2010. Maternal age
      ranged from 17 to 41 years and the gestational age between 37 to 42 weeks
      according to an ultrasound or reliable last menstrual period, as criteria of
      study inclusion. After admission, patients had a vaginal speculum for Preterm
      Premature Rupture of Membranes (PPROM), Abdominal ultrasonography for biometry
      and Amniotic Fluid Index (AFI), transperineal ultrasonography for measuring fetal
      head distance to maternal perineum, and vaginal ultrasonography for measuring
      cervical length and posterior angle of fetal head with cervix were undergone.
      Bishop score was assigned to another person. Labor was induced by administering
      either intravaginal misoprostol (25 microgram every six hours for a Bishop score
      lower than 7) or intravenous oxytocin (low dose regimen for a Bishop score equal
      to or more than 7). RESULTS: Misoprostol was used for 75 patients and 26 patients
      had induction of labor with low dose oxytocin. Eighty one patients had Normal
      Vaginal Delivery (NVD) while 20 were delivered via Cesarean Section. For cervical
      ripening, Bishop Score (p<0.001), cervical length (p=0.04) and parity (p=0.06)
      were predicting factors. The cervical posterior angle p=0.02 had a predicting
      role in natural delivery. CONCLUSION: The cervical posterior angle was a
      predicting factor for natural delivery. Although cervical length, Body Mass Index
      (BMI), and parity were not predicting factors for natural delivery; these factors
      were good predictors for cervical ripening.

PMID- 23979615
TI  - Ultrasound in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by
      synovial inflammation that can lead to structural damage of cartilage, bone and
      tendons. Assessing the inflammatory activity and the severity is essential in RA
      to help rheumatologists in adopting proper therapeutic strategies and in
      evaluating disease outcome and response to treatment. In the last years
      musculoskeletal (MS) ultrasonography (US) underwent tremendous technological
      development of equipment with increased sensitivity in detecting a wide set of
      joint and soft tissues abnormalities. In RA MSUS with the use of Doppler
      modalities is a useful imaging tool to depict inflammatory abnormalities (i.e.
      synovitis, tenosynovitis and bursitis) and structural changes (i.e. bone
      erosions, cartilage damage and tendon lesions). In addition, MSUS has been
      demonstrated to be able to monitor the response to different therapies in RA to
      guide local diagnostic and therapeutic procedures such as biopsy, fluid
      aspirations and injections. Future applications based on the development of new
      tools may improve the role of MSUS in RA. 

PMID- 23979616
TI  - The role of HDlive technology in improving the quality of obstetrical images.
AB  - Imaging techniques have developed remarkably during the recent years. The
      technologic progress made in areas of obstetrics has been spectacular. High
      Definition live (HDlive) ultrasound is the latest novel ultrasound technology
      that improves both three-dimensional or four dimensional ultrasound images. This
      paper illustrates the potential of HDlive technology in the study of the embryo
      and fetus. This technology could be useful in studying the normal embryonic and
      fetal development, as well as in providing informations for fetuses at risk for
      specific congenital malformations by confirming normality. HDlive has a great
      potential in perinatal research and could help to provide a better understanding
      of the development of the early embryo and the fetus. Also, by providing the
      natural pictures of the fetus, HDlive could increase the fetal maternal bonding,
      which is an important element for correct management of the pregnancy. Although
      its advantages need to be further explored, HDlive represents, in our opinion, an
      innovative technique and a useful tool for a more realistic visualization of the
      embryo and the fetus surfaces. 

PMID- 23979617
TI  - The EFSUMB website, a guide for better understanding.
AB  - The aim of the paper is to introduce readers to EFSUMB's wide ranging activities
      which have embraced modern technology. The most recent is the Atlas www.efsumb
      atlas.org primarily introduced to accompany the Elastography, CEUS Liver and Non
      Liver Guidelines but intended to expand to all areas to offer a database of
      images which can be freely downloaded. Hosting eBooks on our website is another
      new departure, most importantly the EFSUMB Course Book on Ultrasound which is
      also in a printed form but allowing chapters to be updated online, an online
      Student Edition of the ECB to be launched at EUROSON 2013. EFSUMB has been active
      with updating Guidelines; those mentioned above have all been revised or written
      in the last two years. The EFSUMB Newsletter in the EJU promotes our activities
      and topical articles intended to reach all our members with the mailing of Issue
      1. The Case of the Month continues to be one of EFSUMB's most visited sites and
      in the last few years has been translated into seven different languages
      including Chinese. IN CONCLUSION this article aims to provide a guide to the
      website educational sites of the European Federation of Societies for Ultrasound
      in Medicine and Biology (EFSUMB).

PMID- 23979618
TI  - Ultrasound guided supraclavicular block.
AB  - Ultrasound guided regional anaesthesia is becoming increasingly popular. The
      supraclavicular block has been transformed by ultrasound guidance into a
      potentially safe superficial block. We reviewed the techniques of performing
      supraclavicular block with special focus on ultrasound guidance. 

PMID- 23979619
TI  - Point-of-care ultrasound in the diagnosis of upper extremity fracture
      dislocation. A pictorial essay.
AB  - Patients commonly present with orthopedic injuries to the emergency department
      (ED). Although radiographs are the standard of care for evaulating these
      injuries, point-of-care ultrasound is being increasingly used to make the
      diagnosis. This modality can be useful in patients who are too clinically
      unstable to leave the acute care ED and in nonverbal pediatric or geriatric
      patients who are unable to isolate their injuries. Published case series and
      prospective studies highlight the emergency physician's (EP) ability to detect
      fractures with point-of-care ultrasound with good accuracy. The American College
      of Emergency Physicians ultrasound guidelines advocate fracture identification as
      within the EP's scope of practice. This pictorial essay reviews how to use point
      of-care ultrasound to diagnose fractures and dislocations of the upper extremity.

PMID- 23979620
TI  - Pentalogy of Cantrell associated with exencephaly and spinal dysraphism:
      antenatal ultrasonographic diagnosis. Case report.
AB  - The pentalogy of Cantrell, a rare syndrome, consists of the defects in the
      anterior diaphragm, diaphragmatic pericardium, lower sternum and supraumbilical
      abdominal wall, along with congenital cardiac abnormalities. Till date, only few
      patients with full spectrum of this syndrome have been reported with only 2 cases
      showing associated exencephaly and spinal dysraphism. We report extremely rare
      association of complete pentalogy of Cantrell syndrome with exencephaly and
      spinal dysraphism on antenatal sonogram and autopsy in a 18 weeks fetus of a 19
      year-old primi gravida female. 

PMID- 23979621
TI  - Uterine artery embolization with methotrexate infusion as treatment for cesarean
      scar pregnancy. Case report.
AB  - Cesarean scar pregnancy is a rare form of ectopic pregnancy. It is associated
      with many complications, including a high risk of massive bleeding and
      hysterectomy under unfavorable conditions. Conservative treatment with systemic
      methotrexate (MTX) has been used preferentially with the aim of allowing the
      patient to have a reproductive future. However, cases of complex ectopic masses
      in a cesarean scar with guarded prognosis demand techniques that are more
      effective, such as uterine artery embolization (UAE) in association with intra
      arterial MTX infusion. We describe the case of a 35-year-old patient in the 8th
      week of pregnancy who was referred to us because of genital bleeding and
      suspected ectopic pregnancy in the cesarean scar. After confirmation of the
      diagnosis, an initial attempt at systemic treatment with MTX was made. This was
      abandoned due to the elevation of the hepatic transaminase level. In addition,
      because of the complexity of the mass and the patient's desire to preserve her
      reproductive capacity, it was decided to perform UAE with local MTX infusion. The
      procedure was performed successfully and the patient's fertility was preserved. 

PMID- 23979622
TI  - Efficacy of ultrasonography in lymphatic malformations: diagnosis, treatment and
      follow-up: a case report.
AB  - Lymphatic malformation (LM) is a localized and rare benign anomaly of the
      lymphatic system. Surgery is the primary form of treatment, but total resection
      is difficult and generally not possible. The least invasive and most effective
      form of treatment is injection sclerotherapy with sclerosing agents. Here, we
      report a case of LM in a baby, detected at prenatal ultrasound. The aim of this
      report is to assess the importance of ultrasonography in the prenatal diagnosis,
      therapy and follow-up of LM's. 

PMID- 23979623
TI  - Ultrasound aspect of mesenteric panniculitis. Case report.
AB  - Mesenteric panniculitis represents a cronic inflammation of the adipose tissue of
      the mesentery which can present sometimes with the imagistic aspect of one or
      multiples pseudotumors. We present the case of female patient in which mesenteric
      panniculitis was found accidentally during a routine abdominal ultrasound
      examination leading to differential diagnostics problems. Color Doppler and
      contrast enhancement ultrasonography were helpful for diagnosis evidencing a
      benign circulatory signal. 

PMID- 23979624
TI  - Young men with bilateral pain in the lower part of patella.

PMID- 23979625
TI  - The subcutaneous implantable defibrillator: a new technology that raises an
      existential question for the implantable cardioverter-defibrillator.

PMID- 23979626
TI  - Safety and efficacy of a totally subcutaneous implantable-cardioverter
      defibrillator.
AB  - BACKGROUND: The most frequent complications associated with implantable
      cardioverter-defibrillators (ICDs) involve the transvenous leads. A subcutaneous
      implantable cardioverter-defibrillator (S-ICD) has been developed as an
      alternative system. This study evaluated the safety and effectiveness of the S
      ICD System (Cameron Health/Boston Scientific) for the treatment of life
      threatening ventricular arrhythmias (ventricular tachycardia/ventricular
      fibrillation). METHODS AND RESULTS: This prospective, nonrandomized, multicenter
      trial included adult patients with a standard indication for an ICD, who neither
      required pacing nor had documented pace-terminable ventricular tachycardia. The
      primary safety end point was the 180-day S-ICD System complication-free rate
      compared with a prespecified performance goal of 79%. The primary effectiveness
      end point was the induced ventricular fibrillation conversion rate compared with
      a prespecified performance goal of 88%, with success defined as 2 consecutive
      ventricular fibrillation conversions of 4 attempts. Detection and conversion of
      spontaneous episodes were also evaluated. Device implantation was attempted in
      321 of 330 enrolled patients, and 314 patients underwent successful implantation.
      The cohort was followed for a mean duration of 11 months. The study population
      was 74% male with a mean age of 52+/-16 years and mean left ventricular ejection
      fraction of 36+/-16%. A previous transvenous ICD had been implanted in 13%. Both
      primary end points were met: The 180-day system complication-free rate was 99%,
      and sensitivity analysis of the acute ventricular fibrillation conversion rate
      was >90% in the entire cohort. There were 38 discrete spontaneous episodes of
      ventricular tachycardia/ventricular fibrillation recorded in 21 patients (6.7%),
      all of which successfully converted. Forty-one patients (13.1%) received an
      inappropriate shock. CONCLUSIONS: The findings support the efficacy and safety of
      the S-ICD System for the treatment of life-threatening ventricular arrhythmias.

PMID- 23979627
TI  - Waveform analysis-guided treatment versus a standard shock-first protocol for the
      treatment of out-of-hospital cardiac arrest presenting in ventricular
      fibrillation: results of an international randomized, controlled trial.
AB  - BACKGROUND: Ventricular fibrillation (VF) waveform properties have been shown to
      predict defibrillation success and outcomes among patients treated with immediate
      defibrillation. We postulated that a waveform analysis algorithm could be used to
      identify VF unlikely to respond to immediate defibrillation, allowing selective
      initial treatment with cardiopulmonary resuscitation in an effort to improve
      overall survival. METHODS AND RESULTS: In a multicenter, double-blind, randomized
      study, out-of-hospital cardiac arrest patients in 2 urban emergency medical
      services systems were treated with automated external defibrillators using either
      a VF waveform analysis algorithm or the standard shock-first protocol. The VF
      waveform analysis used a predefined threshold value below which return of
      spontaneous circulation (ROSC) was unlikely with immediate defibrillation,
      allowing selective treatment with a 2-minute interval of cardiopulmonary
      resuscitation before initial defibrillation. The primary end point was survival
      to hospital discharge. Secondary end points included ROSC, sustained ROSC, and
      survival to hospital admission. Of 6738 patients enrolled, 987 patients with VF
      of primary cardiac origin were included in the primary analysis. No immediate or
      long-term survival benefit was noted for either treatment algorithm (ROSC, 42.5%
      versus 41.2%, P=0.70; sustained ROSC, 32.4% versus 33.4%, P=0.79; survival to
      admission, 34.1% versus 36.4%, P=0.46; survival to hospital discharge, 15.6%
      versus 17.2%, P=0.55, respectively). CONCLUSIONS: Use of a waveform analysis
      algorithm to guide the initial treatment of out-of-hospital cardiac arrest
      patients presenting in VF did not improve overall survival compared with a
      standard shock-first protocol. Further study is recommended to examine the role
      of waveform analysis for the guided management of VF.

PMID- 23979629
TI  - Device infections: management and indications for lead extraction.

PMID- 23979631
TI  - A unique case of quadricuspid aortic valve with coronary artery and descending
      aorta-to-pulmonary artery fistulae.

PMID- 23979632
TI  - Asymptomatic rupture of the left ventricle.

PMID- 23979628
TI  - Pathological ventricular remodeling: therapies: part 2 of 2.

PMID- 23979634
TI  - Letter by Rassi and Rassi regarding article, "Ten-year incidence of Chagas
      cardiomyopathy among asymptomatic, Trypanosoma cruzi-seropositive former blood
      donors".

PMID- 23979635
TI  - Letter by Bestetti and Cardinalli-Neto regarding article, "Ten-year incidence of
      Chagas cardiomyopathy among asymptomatic, Trypanosoma cruzi-seropositive former
      blood donors".

PMID- 23979636
TI  - Response to letters regarding article, "Ten-year incidence of Chagas
      cardiomyopathy among asymptomatic, Trypanosoma cruzi-seropositive former blood
      donors".

PMID- 23979637
TI  - Metabolic syndrome, inflammation and atherothrombosis.
AB  - Extensive research of the past decades altered our traditional concept about the
      genesis of atherosclerosis fundamentally. Today, the crucial role of inflammation
      in the formation and progression of atherosclerotic plaques is indisputable.
      Patients at high risk for developing cardiovascular disease, owing to poor diet,
      obesity and low physical activity have been shown to exhibit a particular
      inflammatory pattern. Therefore, the present review highlights the crosslink
      between the metabolic syndrome (MetS), adipose tissue, adipokines and selected
      inflammatory cytokines in the context of atherothrombosis and cardiovascular
      disease. 

PMID- 23979639
TI  - Five compounds for treating diabetes-related conditions.

PMID- 23979641
TI  - Treating canine hepatic disease.

PMID- 23979640
TI  - Case report: topical gel for the treatment of a refractory leg ulcer.

PMID- 23979642
TI  - Incubators.

PMID- 23979643
TI  - Further Clarification of HIPAA Regulations.

PMID- 23979644
TI  - Accuracy of graduated cylinders.

PMID- 23979645
TI  - Product containment in the compounding laboratory.

PMID- 23979646
TI  - Quality-Control Analytical Methods: Principles of pH.

PMID- 23979647
TI  - Stability of Amikacin Sulfate in AutoDose Infusion System Bags.
AB  - The objective of this study was to evaluate the physical and chemical stability
      of amikacin 25mg/100mL and 500mg/100mL as the sulfate salt admixed in 0.9% sodium
      chloride injection and packaged in AutoDose Infusion System bags. Triplicate test
      samples of each concentration were prepared by admixing the necessary amounts of
      the amikacin sulfate with a portion of 0.9% sodium chloride injection. The
      admixtures were brought to a final volume of 100mL with additional 0.9% sodium
      shloride injection. The test solutions were packaged in AutoDose bags, which are
      ethylene vinyl acetate plastic containers designed for use in the AutoDose
      Infusion System. Samples were stored protected from light and evaluated at
      appropriate intervals for up to 7 days at 23 deg C and up to 30 days at 4 deg C.
      Physical stability was assessed by means of a multistep evaluation procedure that
      included both turbidimetric and particulate measurement, as well as visual
      inspection. Chemical stability was assessed by stability-indicating high
      performance liquid chromatographic analytical techniques based on the
      determination of initial drug concentrations and drug concentrations at
      appropriate intervals over the study periods. The amikacin sulfate admixtures
      were clear and colorless when viewed in normal fluorescent room light and when
      viewed with a Tyndall beam. Measured turbidity and particulate content were low
      and exhibited little change. High-performance liquid chromatographic analysis
      indicated that the amikacin sulfate remained stable for 30 days at 4 deg C and
      for 7 days at 23 deg C. At both concentrations, amikacin sulfate exhibited
      physical and chemical stability consistent with previous studies of this drug.
      The AutoDose Infusion System bags did not adversely affect the physical and
      chemical stability of the amikacin sulfate. 

PMID- 23979648
TI  - Formulation development and stabililty testing of extemporaneous suspension
      prepared from dapsone tablets.
AB  - The qualification and quantification of dapsone in suspension were developed and
      shown to be stability indicating by means of a reverse-phase high-performance
      liquid chromatographic method. The real solubility of dapsone in water was
      calculated to be 0.208mg/mL at 25 deg C. The enthalpy of solution and the entropy
      of solution were calculated to be -175.6 J/g and -43605.7 J/K/M, respectively. An
      extemporaneous suspension was formulated from commercially available dapsone
      rablets, and the chemical stability of dapsone in the suspension was determined
      by means of accelerated stability testing. The 91-day analytical stabilty testing
      study was conducted at 4, 30, 50, 60, and 70 deg C. The energy of activation for
      the suspension was determined to be -23288.35 J/K/M. The zero-order rate of
      degradation for dapsone (k0,25) in suspension at 25 deg C was found to be
      0.040845 day -1. The first-order rate of degradation for dapsone in solution was
      found to be 0.196370 (mg/mL)(day-1). The shelf life for the suspension was
      calulated to be 31.67 days at 25 deg C and 230.76 days under refrigeration at 4
      deg C. 

PMID- 23979649
TI  - Can the ICF be used as a rehabilitation outcome measure? A study looking at the
      inter- and intra-rater reliability of ICF categories derived from an ADL
      assessment tool.
AB  - PURPOSE: The categories of the International Classification of Functioning ,
      Disability and Health (ICF) could potentially be used as components of outcome
      measures. Literature demonstrating the psychometric properties of ICF categories
      is limited. OBJECTIVE: Determine the agreement and reliability of ICF activities
      of daily living category scores and compare these to agreement and reliability of
      the Functional Independence Measure (FIM) item scores. METHOD: Two investigators
      independently reviewed the clinical notes to score the ICF activities of daily
      living cate-gories, of 100 patients using ICF qualifiers with additional scoring
      guidelines. The percentage agreement, interrater and intrarater reliability were
      compared with the matched FIM items scored by a separate set of two investigators
      using the same methodology. Kappa Statistic was calculated using Med Calc.
      RESULTS: ICF interrater reliability as indicated by Kappa values ranging from
      0.42 to 0.81 was moderate or better for the eleven self care and mobility
      categories. The language ICF categories and problem solving generally have fair
      agreement, with Kappa values ranging from 0.21 for receiving verbal messages to
      0.44 for basic social interactions. Absolute agreement was above 72% for all
      categories. Reliability and agreement of the FIM items was generally lower than
      the corresponding ICF categories. CONCLUSION: The inter-rater and intra-rater
      reliability and agreement of the ICF activities of daily living categories were
      comparable or better than the corresponding FIM items. The results of this study
      provide an indication that the ICF categories could be used as components of
      rehabilitation outcome measures.

PMID- 23979650
TI  - Differential diagnosis of small cell glioblastoma and anaplastic
      oligodendroglioma: a case report of an elderly man.
AB  - Small cell glioblastoma is a histological subtype of glioblastoma with
      characteristic features of highly proliferative, monotonous small glial cells
      with high nuclear cytoplasm ratio. Morphologically, malignant lymphoma or small
      cell metastatic carcinoma should be carefully discriminated. Some cases are
      difficult to differentiate from anaplastic oligodendroglioma. In this report, we
      present a case of small cell glioblastoma of an elderly man. The lack of IDH1/2
      mutation was confirmed by immunohistochemistry and direct sequencing.
      Fluorescence in situ hybridization revealed the lower rates of chromosome 1p and
      19q deletion. Microsatellite analysis disclosed partial 10q alteration near the
      PTEN locus. Not only morphological and immunohistochemical examinations, but also
      cytogenetical investigations for IDH1/2 mutation, 1p/19q loss, and PTEN
      alteration, are strongly supportive methods for the differential diagnosis of
      small cell glioblastoma and anaplastic oligodendroglioma.

PMID- 23979651
TI  - Open letter to the European Commission: scientifically unfounded precaution
      drives European Commission's recommendations on EDC regulation, while defying
      common sense, well-established science, and risk assessment principles.

PMID- 23979652
TI  - Circulating acylcarnitines as biomarkers of mitochondrial dysfunction after
      acetaminophen overdose in mice and humans.
AB  - Acetaminophen (APAP) is a widely used analgesic. However, APAP overdose is
      hepatotoxic and is the primary cause of acute liver failure in the developed
      world. The mechanism of APAP-induced liver injury begins with protein binding and
      involves mitochondrial dysfunction and oxidative stress. Recent efforts to
      discover blood biomarkers of mitochondrial damage have identified increased
      plasma glutamate dehydrogenase activity and mitochondrial DNA concentration in
      APAP overdose patients. However, a problem with these markers is that they are
      too large to be released from cells without cell death or loss of membrane
      integrity. Metabolomic studies are more likely to reveal biomarkers that are
      useful at early time points, before injury begins. Similar to earlier work, our
      metabolomic studies revealed that acylcarnitines are elevated in serum from mice
      after treatment with toxic doses of APAP. Importantly, a comparison with
      furosemide demonstrated that increased serum acylcarnitines are specific for
      mitochondrial dysfunction. However, when we measured these compounds in plasma
      from humans with liver injury after APAP overdose, we could not detect any
      significant differences from control groups. Further experiments with mice showed
      that N-acetylcysteine, the antidote for APAP overdose in humans, can reduce
      acylcarnitine levels in serum. Altogether, our data do not support the clinical
      measurement of acylcarnitines in blood after APAP overdose due to the standard N
      acetylcysteine treatment in patients, but strongly suggest that acylcarnitines
      would be useful mechanistic biomarkers in other forms of liver injury involving
      mitochondrial dysfunction. 

PMID- 23979653
TI  - The importance, and important limitations, of ultrasound imaging for evaluating
      thyroid nodules.

PMID- 23979654
TI  - Amblyomma parvitarsum (Acari: Ixodidae): localities, hosts and host-parasite
      ecology.
AB  - Only a few aspects of the biology of Amblyomma parvitarsum Neumann are known.
      Adults of this hard tick species are parasites of South American camelids in the
      Andean plateau of Argentina, Bolivia, Peru and Chile and also in the Argentine
      Patagonia, but they have been also rarely found on other artyodactils and two
      species of birds. The larva has been collected from reptiles in northern Chile,
      whereas the hosts for the nymph remain unknown. On nine localities included
      within Altitude Tropical and Perarid Mediterranean ecoregions in northern Chile,
      we analyzed 237 reptiles, 285 birds, 624 rodents and 52 camelids for infestation
      with A. parvitarsum to calculate seasonal prevalence of this tick. We also
      reviewed the literature of this tick and three entomological collections for
      obtaining and summarizing all the information to date about this tick. None of
      the analyzed birds and rodents were parasitized with A. parvitarsum; however,
      seven over a total of ten reptile species that we caught were infested with the
      larva. In the camelid species Lama glama and Vicugna pacos we collected adult
      specimens of this tick. Larval prevalence was higher during fall (75 %) in
      Liolaemus pleopholis in the Altitude Tropical ecoregion. We also collected adult
      specimens of A. parvitarsum from camelid manure heaps during summer in Salar de
      Surire and Llullaillaco localities. Additionally, we also reviewed the literature
      of this tick and examined specimens in three entomological collections for
      obtaining and summarizing all the information to date about this tick. By this
      study, nine localities and seven new hosts are added for A. parvitarsum and we
      confirm reptiles as specific hosts of this tick larva.

PMID- 23979655
TI  - Comparative toxicity of pesticides in three phytoseiid mites with different life
      style occurring in citrus: Euseius stipulatus, Neoseiulus californicus and
      Phytoseiulus persimilis.
AB  - Conservation and augmentative biological control strategies have been developed
      to take full advantage of the natural enemies that occur in Spanish citrus
      orchards. Among them, the predatory mites Euseius stipulatus, Neoseiulus
      californicus and Phytoseiulus persimilis play an important role in the biological
      control of tetranychid mites. However, these predatory mites are often affected
      by pesticides and information about the side-effects of these products against
      these beneficial arthropods is essential to guarantee their efficacy. The side
      effects of some pesticides remain unknown and the primary aim of this study was
      to fill this gap. We have further used this information and that collected from
      other sources to compare the response of these three mite species to pesticides.
      Based on this information, E. stipulatus has the most tolerant species, followed
      by N. californicus and P. persimilis. Therefore, using E. stipulatus as an
      indicator species in citrus may have led to the paradox of selecting presumed
      selective pesticides resulting in excessive impact on N. californicus and,
      especially on P. persimilis. Because these two latter species are considered key
      for the biological control of T. urticae in citrus, especially clementines, in
      Spain, we propose to use P. persimilis as the relevant indicator of such effects
      on predacious mites occurring in citrus instead of E. stipulatus. This change
      could have a dramatic impact on the satisfactory control of tetranychid mites in
      citrus in the near future. 

PMID- 23979656
TI  - Observations on the removal of brood inoculated with Tropilaelaps mercedesae
      (Acari: Laelapidae) and the mite's reproductive success in Apis mellifera
      colonies.
AB  - This study assessed the response of Apis mellifera to brood deliberately infested
      with Tropilaelaps mercedesae. The reproductive success of T. mercedesae in mite
      inoculated and naturally infested brood was also compared. The presence of T.
      mercedesae inside brood cells significantly affected brood removal. Thai A.
      mellifera removed 52.6 +/- 8.2 % of the brood inoculated with T. mercedesae as
      compared to 17.2 +/- 1.8 and 5.7 +/- 1.1 % removal rates for the groups of brood
      with their cell cappings opened and closed without mite inoculation and the
      control brood (undisturbed, no mite inoculation), respectively. Brood removal
      peaked during the second and third days post inoculation when test brood was at
      the prepupal stage. Overall, non-reproduction (NR) of foundress T. mercedesae was
      high. However, when NR was measured based on the criteria used for Varroa, the
      naturally infested pupae (NIP) supported the highest NR (92.8 %). Newly sealed
      larvae inoculated with Tropilaelaps collected from newly sealed larvae (NSL) had
      78.2 % NR and those inoculated with Tropilaelaps collected from tan-bodied pupae
      (TBP) had 76.8 % NR. Since Tropilaelaps is known to have a short development
      period and nearly all progeny reach adulthood by the time of host emergence, we
      also used two Tropilaelaps-specific criteria to determine NR. Foundresses that
      did not produce progeny and those that produced only one progeny were considered
      NR. Using these two criteria, NR decreased tremendously but showed similar trends
      with means of 65, 40 and 33 % for NIP, NSL and TBP, respectively. High NR in the
      NIP group may indicate increased hygienic behavior in Thai A. mellifera colonies.
      The removal of infested prepupae or tan-bodied pupae will likely decrease the
      reproductive potential of Tropilaelaps. Our study suggests that brood removal may
      be one of the resistance mechanisms towards T. mercedesae by naturally adapted
      Thai A. mellifera.

PMID- 23979657
TI  - The baseline NIHSS score in female and male patients and short-time outcome: a
      study in young ischemic stroke.
AB  - The NIH Stroke Scale (NIHSS) may not appropriately assess the spectrum of young
      sex-related stroke neurologic deficits. We determined the cutoff baseline NIHSS
      score that predicts independent daily life activity at discharge in young male
      versus female ischemic strokes. We conducted this study in 1,451 young Chinese
      adults with acute cerebral ischemic stroke as determined by the modified Rankin
      Scale (mRS) at discharge. The main outcome measures included a composite
      favorable outcome (defined as a mRS score of 0 or 2) and poor outcome (defined as
      a mRS score of 3 or 6) at discharge. Bivariate logistic regression analyses were
      used to determine the risk factors of outcome at discharge in male and female
      patients respectively, receiver operating characteristic (ROC) curves and
      calculated the area under the ROC curve with 95 % CIs. P < 0.05 was considered
      significant. Stepwise logistic regression analysis confirmed the risk factors of
      outcome included: diabetes mellitus, hyperlipidemia, stroke subtype and baseline
      NIHSS score in male patient; atrial fibrillation, stroke subtype and baseline
      NIHSS score in female patients. The optimal cutoff score of the baseline NIHSS
      was <=4 for female patients with stroke, the optimal cutoff score of the baseline
      NIHSS was <=6 for male patients with stroke. The cutoff score of the baseline
      NIHSS for a favorable outcome at discharge was relatively low in young female
      patients compared to male patients. These results need further confirmation in
      larger contemporary datasets. 

PMID- 23979658
TI  - Hair magnesium, but not serum magnesium, is associated with left ventricular wall
      thickness in hemodialysis patients.
AB  - BACKGROUND: Extracellular magnesium (Mg) accounts for approximately 1% of the
      total body Mg. Clinically, serum Mg concentration is measured, but it does not
      necessarily reflect total body Mg status. Although relationships have been
      reported between reduced Mg and cardiovascular disease in non-dialysis patients,
      there have been few such studies in hemodialysis patients. It was hypothesized
      that reduced Mg, as represented by lower Mg concentration in the hair, would be
      associated with echocardiographic parameters in chronic hemodialysis patients.
      METHODS AND RESULTS: Hair Mg concentration was measured in 79 male hemodialysis
      patients using inductively coupled plasma mass spectrometry, and the
      relationships between hair Mg concentration and echocardiographic parameters were
      investigated. There was no significant correlation between Mg concentration in
      the hair and in serum. Hair Mg concentration in the patients with high-left
      ventricular mass index (LVMI) was significantly lower than that in the low-LVMI
      patients. Hair Mg concentration correlated significantly and negatively with
      posterior left ventricular wall thickness, interventricular septum thickness,
      left ventricular wall thickness (LVWT), and relative wall thickness. Serum Mg
      concentration, however, did not correlate with any of these echocardiographic
      parameters. CONCLUSIONS: In hemodialysis patients, hair Mg concentration is a
      biomarker, independent of serum Mg concentration. Hair Mg, but not serum Mg, was
      significantly and negatively associated with LVWT. Reduced tissue Mg
      concentration, as measured in the hair, may be associated with left ventricular
      hypertrophy in hemodialysis patients.

PMID- 23979659
TI  - The future of bladder cancer care in the USA.
AB  - Bladder cancer is the fifth most common malignancy in the USA and the most
      expensive to treat on a per-patient basis. Despite its prevalence, morbidity,
      mortality and associated cost of management, bladder cancer remains grossly under
      recognized as a public health concern and underfunded scientifically. Although 5
      year survival rates for patients with prostate or kidney cancer have improved
      tremendously in the past 30 years, progress in bladder cancer has stalled. A
      renewed interest from the clinical and research communities, as well as a young
      and eager advocacy network, are raising the profile of bladder cancer. As
      awareness and funding of bladder cancer increase, improved diagnostics,
      therapeutics and health services for patients with the disease will develop
      accordingly. 

PMID- 23979660
TI  - Prostate cancer: Focal cryotherapy freezes recurrent disease in its tracks.

PMID- 23979661
TI  - Bladder cancer: aristolochic acid--one of the most potent carcinogens known to
      man.

PMID- 23979664
TI  - Prostate cancer: Not guilty-TMPRSS2-ERG does not sensitize cells to radiation.

PMID- 23979665
TI  - Prostate cancer: PSA enzymatic activity to assess disease aggressiveness.

PMID- 23979669
TI  - Drinking and swimming: investigating young Australian males' intentions to engage
      in recreational swimming while under the influence of alcohol.
AB  - Drowning, a largely preventable problem, continues to be a serious issue
      worldwide, with young men particularly at risk. Alcohol and drugs are often
      present among young males and, particularly for males aged 18-34 years, alcohol
      is considered to be a significant risk factor for drowning. The current study
      aimed to understand the motivations guiding the intentions of young Australian
      men to engage in drinking and swimming, a behaviour not yet examined
      systematically. A cross-sectional correlational design was adopted to investigate
      the ability of the theory of planned behaviour (TPB) and additional variables to
      predict males' intentions to drink and swim. Males (N = 211) aged 18-34 years
      (Mage = 23.93, SD = 4.01) completed a survey either on-line or paper-based. The
      survey assessed the TPB constructs of attitude, subjective norm, and perceived
      behavioural control (PBC); and additional variables of group norms, anticipated
      regret, objective (i.e. swimming ability) and perceived (i.e. perceived severity
      and perceived susceptibility) risk perceptions, and past behaviour. Support was
      found for the TPB constructs of attitude and subjective norm, but not PBC, as
      well as the additional constructs of group norm, anticipated regret, objective
      risk, and past behaviour in predicting males' intentions to drink and swim;
      explaining an overall 76 % of variance. Knowledge gained from this study will
      help to inform resultant interventions designed to discourage alcohol use in, on,
      or around water and, thus, prevent drownings in this at risk group. 

PMID- 23979670
TI  - The role of cosmetologists as health promoters in the prevention of infant
      mortality.
AB  - Safe sleep practices reduce an infant's risk for sudden infant death syndrome and
      sleep-related death. While rates of infants placed on their back to sleep are
      high, other safe sleep practices are less widely implemented. Our objective was
      to evaluate the feasibility of using cosmetologists as health promoters for
      infant safe sleep to reduce infant mortality. In this descriptive study, a 27
      item survey was mailed to the 405 licensed cosmetologists residing in the five
      zip codes with the highest infant mortality rates in the county. Of 149 completed
      surveys (36.8 %), 103 cosmetologists (69.1 %) were currently working. Most were
      comfortable (68.9 %) promoting health topics with their clients. Popular health
      related topics currently discussed included: diet/weight control, healthy eating,
      and physical activity. Few (<=13 %) were interested in discussing infant
      mortality prevention or safe sleep promotion. Most respondents were either unsure
      (56 %) or did not feel infant mortality was a problem in their community (41 %);
      however, more than half (53 %) knew someone who had experienced an infant death.
      Cosmetologists were not highly interested in providing safe sleep education;
      however they engaged in diet and exercise talk already. Cosmetologists may be
      more appropriate for obesity-prevention programs to reduce infant mortality than
      safe sleep promotion.

PMID- 23979666
TI  - Toll-like receptors in urothelial cells--targets for cancer immunotherapy.
AB  - Toll-like receptors (TLRs) have an important role in the activation of both
      innate and adaptive immunity in response to pathogens and danger signals. These
      receptors are expressed in immune cells and in some epithelia. They are expressed
      in the epithelium of the urinary bladder, where they actively participate in the
      fight against infection by uropathogens. TLR expression is decreased (although
      still evident) in bladder tumours, especially in non-muscle-invasive tumours.
      Intravesical immunotherapy with BCG to prevent recurrence of these tumours has
      been shown to involve the participation of three different TLRs (TLR2, TLR4, and
      TLR9). However, alternative therapies are needed as BCG fails in some patients
      and can sometimes cause severe adverse effects that are difficult to tolerate. In
      recent years, TLR2, TLR4, TLR7, and TLR9 agonists have been tested in vitro and
      in vivo for their ability to activate an antitumour immune response against
      bladder cancer. Promising results from these studies have led to the testing of
      TLR7 and TLR9 agonists in clinical trials. 

PMID- 23979671
TI  - Differences among college women for breast cancer prevention acquired information
      seeking, desired apps and texts, and daughter-initiated information to mothers.
AB  - The purpose of this study was to examine among college women acquired breast
      cancer prevention information-seeking, desired apps and texts, and information
      given to mothers. Using a cross-sectional study, a survey was administered to
      college women at a southwestern university. College women (n = 546) used the
      Internet (44 %) for active breast cancer prevention information-seeking and used
      the Internet (74 %), magazines (69 %), and television (59 %) for passive
      information receipt. Over half of the participants desired breast cancer
      prevention apps (54 %) and texts (51 %). Logistic regression analyses revealed
      predictors for interest to receive apps were ethnicity (Hispanic), lower self
      efficacy, actively seeking online information, and older age and predictors for
      interest to receive texts were lower self-efficacy and higher university level.
      Eighteen percent of college women (n = 99) reported giving information to mothers
      and reported in an open-ended item the types of information given to mothers.
      Predictors for giving information to mothers were actively and passively seeking
      online information, breast self-exam practice, and higher university level.
      Screenings were the most frequent types of information given to mothers. Breast
      cancer prevention information using apps, texts, or Internet and daughter
      initiated information for mothers should be considered in health promotion
      targeting college students or young women in communities. Future research is
      needed to examine the quality of apps, texts, and online information and cultural
      differences for breast cancer prevention sources.

PMID- 23979672
TI  - Synthesis, structure, spectral and electrochemical properties of B(OR)2
      smaragdyrin complexes.
AB  - A series of B(OR)2-smaragdyrin complexes were synthesized by treating BF2
      smaragdyrin complex with various aliphatic and aromatic alcohols in the presence
      of AlCl3 in CH2Cl2 at room temperature. The compounds are stable and
      characterized by various spectroscopic and electrochemical techniques. The X-ray
      structure solved for one of the B(OR)2-smaragdyrin complex showed that the
      macrocycle is planar and the boron atom is in tetrahedral geometry coordinated to
      two pyrrole nitrogens of the macrocycle and two oxygen atoms of the axial -OR
      groups. (1)H NMR studies indicated that the alkoxy or aryloxy groups present on
      the boron atom experience the macrocyclic ring current effect and appear in the
      up-field region. The absorption properties of B(OR)2-smaragdyrin complexes showed
      a strong absorption band at ~700 nm along with other absorption bands in the 450
      650 nm region like BF2-smaragdyrin complex. Since B(OR)2-smaragdyrin complexes
      are electron rich due to the presence of electron rich alkoxy and aryloxy groups,
      the B(OR)2-smaragdyrin complexes are easier to oxidize but difficult to reduce
      compared to BF2-smaragdyrin. The B(OR)2-smaragdyrin complexes are found to be
      weakly fluorescent than BF2-smaragdyrin.

PMID- 23979674
TI  - A fiber-optic redox sensor for the iron(III)-iron(II) transition.
AB  - A phenosafranine-containing Nafion film attached to the distal end of a fiber
      optic probe forms a functional redox-sensitive optical sensor. The synthetic
      cationic photoactive dye phenosafranine, 3,7-diamino-5-phenylphenazinium
      chloride, responds with changes in light absorbance between its oxidized and
      reduced forms. This optical property persists when phenosafranine is sorbed into
      Nafion, a perfluorosulfonate anionic film. Optical properties of the sensor are
      similar to those seen by others in solution. At high redox conditions, such as an
      open nitrogen-purged aqueous pH 6.5 solution, optical absorbance of
      phenosafranine is high, while at low redox conditions, such as an aqueous pH 6.5
      iron(II) solution, optical absorbance of phenosafranine is low. Titration of a
      closed pH 6.5 aqueous solution with a standard iron(II) solution lowers redox
      potential in a predictable manner and can be followed by the optical redox sensor
      in parallel with a commercial redox potential electrode. 

PMID- 23979675
TI  - Evaluation of metals in several varieties of sweet potatoes (Ipomoea batatas L.):
      comparative study.
AB  - Sweet potatoes are a staple in the diet of some people and an excellent source of
      minerals. Metal monitoring in food, like sweet potatoes, provides basic
      information on safety aspects in regulatory processes as well as nutritional
      values. One hundred five samples of three varieties of sweet potatoes were
      randomly obtained from supermarkets, farmers markets, and farmers' plots in
      Tenerife (Canary Islands, Spain). The edible portion (pulp) was the only part
      considered for analysis. Flame atomic absorption spectrometry was used to
      determine the contents of sodium (Na), potassium (K), calcium (Ca), magnesium
      (Mg), copper (Cu), iron (Fe), manganese (Mn), and zinc (Zn), while the levels of
      chromium (Cr), nickel (Ni), cadmium (Cd), and lead (Pb) were determined using
      graphite furnace atomic absorption spectrometry. The mean concentrations were 500
      Na, 4409 K, 564 Ca, 609 Mg, 1.291 Cu, 6.554 Fe, 2.324 Mn, 2.348 Zn, 0.028 Cr,
      0.048 Ni, 0.001 Cd, and 0.003 Pb mg/kg, respectively. Potassium presented the
      highest contents in all varieties of sweet potatoes. Iron was the most abundant
      microelement. The orange fleshed sweet potato variety offered greater nutritional
      contributions to the recommended intakes than the rest of the varieties studied.
      The estimated mean daily intake of Ni (0.72 mg/day) detected in our samples was
      highly consistent with other studies. Average daily intakes of Cd (0.015 MUg/day)
      and Pb (0.045 MUg/day) were below toxicological reference values. In conclusion,
      the levels of Cd and Pb detected in the sweet potatoes analyzed do not represent
      any toxicological risk to consumers. 

PMID- 23979673
TI  - Zinc and insulin in pancreatic beta-cells.
AB  - Zinc (Zn2+) is an essential element crucial for growth and development, and also
      plays a role in cell signaling for cellular processes like cell division and
      apoptosis. In the mammalian pancreas, Zn2+ is essential for the correct
      processing, storage, secretion, and action of insulin in beta (beta)-cells.
      Insulin is stored inside secretory vesicles or granules, where two Zn2+ ions
      coordinate six insulin monomers to form the hexameric-structure on which
      maturated insulin crystals are based. The total Zn2+ content of the mammalian
      pancreas is among the highest in the body, and Zn2+ concentration reach
      millimolar levels in the interior of the dense-core granule. Changes in Zn2+
      levels in the pancreas have been found to be associated with diabetes. Hence, the
      relationship between co-stored Zn2+ and insulin undoubtedly is critical to normal
      beta-cell function. The advances in the field of Zn2+ biology over the last
      decade have facilitated our understanding of Zn2+ trafficking, its intracellular
      distribution and its storage. When exocytosis of insulin occurs, insulin granules
      fuse with the beta-cell plasma membrane and release their contents, i.e., insulin
      as well as substantial amount of free Zn2+, into the extracellular space and the
      local circulation. Studies increasingly indicate that secreted Zn2+ has autocrine
      or paracrine signaling in beta-cells or the neighboring cells. This review
      discusses the Zn2+ homeostasis in beta-cells with emphasis on the potential
      signaling role of Zn2+ to islet biology.

PMID- 23979676
TI  - Trophic dynamics of U, Ni, Hg and other contaminants of potential concern on the
      Department of Energy's Savannah River Site.
AB  - The Department of Energy's Savannah River Site is a former nuclear weapon
      material production and current research facility located in South Carolina, USA.
      Wastewater discharges from a fuel and nuclear reactor target manufacturing
      facility released depleted and natural U, as well as other metals into the Tims
      Branch-Steed Pond water system. We investigated the current dynamics of this
      system for the purposes of environmental monitoring and assessment by examining
      metal concentrations, bioavailability, and trophic transfer of contaminants in
      seven ponds. Biofilm, detritus, and Anuran and Anisopteran larvae were collected
      and analyzed for stable isotopes (delta (15)N, delta (13)C) and contaminants of
      potential concern (COPC) with a focus on Ni, U, and Hg, to examine metal
      mobility. Highest levels of Ni and U were found in biofilms U (147 and 332 mg kg(
      1) DW, respectively), while highest Hg levels were found in tadpoles (1.1 mg kg(
      1) DW). We found intraspecific biomagnification of COPCs as expressed through
      stable isotope analysis. Biofilms were the best indicators for contamination and
      Anuran larvae with the digestive tract removed were the best indicators of the
      specific bioavailability of the focal metals. Monitoring data showed that
      baseline delta (15)N values differed between ponds, but within a pond, values
      were stable throughout tadpole Gosner stage, strengthening the case to use this
      species for monitoring purposes. It is likely that there still is risk to
      ecosystem integrity as COPC metals are being assimilated into lower trophic
      organisms and even low levels of this mixture has shown to produce deleterious
      effects to some wildlife species. 

PMID- 23979677
TI  - Extraordinary phylogenetic diversity and metabolic versatility in aquifer
      sediment.
AB  - Microorganisms in the subsurface represent a substantial but poorly understood
      component of the Earth's biosphere. Subsurface environments are complex and
      difficult to characterize; thus, their microbiota have remained as a 'dark
      matter' of the carbon and other biogeochemical cycles. Here we deeply sequence
      two sediment-hosted microbial communities from an aquifer adjacent to the
      Colorado River, CO, USA. No single organism represents more than ~1% of either
      community. Remarkably, many bacteria and archaea in these communities are novel
      at the phylum level or belong to phyla lacking a sequenced representative. The
      dominant organism in deeper sediment, RBG-1, is a member of a new phylum. On the
      basis of its reconstructed complete genome, RBG-1 is metabolically versatile. Its
      wide respiration-based repertoire may enable it to respond to the fluctuating
      redox environment close to the water table. We document extraordinary microbial
      novelty and the importance of previously unknown lineages in sediment
      biogeochemical transformations. 

PMID- 23979678
TI  - Hatching asynchrony that maintains egg viability also reduces brood reduction in
      a subtropical bird.
AB  - In birds, hatching failure is pervasive and incurs an energetic and reproductive
      cost to breeding individuals. The egg viability hypothesis posits that exposure
      to warm temperatures prior to incubation decreases viability of early laid eggs
      and predicts that females in warm environments minimize hatching failure by
      beginning incubation earlier in the laying period, laying smaller clutches, or
      both. However, beginning incubation prior to clutch completion may incur a cost
      by increasing hatching asynchrony and possibly brood reduction. We examined
      whether Florida scrub jays (Aphelocoma coerulescens) began incubation earlier
      relative to clutch completion when laying larger clutches or when ambient
      temperatures increased, and whether variation in incubation onset influenced
      subsequent patterns of hatching asynchrony and brood reduction. We compared these
      patterns between a suburban and wildland site because site-specific differences
      in hatching failure match a priori predictions of the egg viability hypothesis.
      Females at both sites began incubation earlier relative to clutch completion when
      laying larger clutches and as ambient temperatures increased. Incubation onset
      was correlated with patterns of hatching asynchrony at both sites; however, brood
      reduction increased only in the suburbs, where nestling food is limiting, and
      only during the late nestling period. Hatching asynchrony may be an unintended
      consequence of beginning incubation early to minimize hatching failure of early
      laid eggs. Food limitation in the suburbs appears to result in increased brood
      reduction in large clutches that hatch asynchronously. Therefore, site-specific
      rates of brood reduction may be a consequence of asynchronous hatching patterns
      that result from parental effort to minimize hatching failure in first-laid eggs.
      This illustrates how anthropogenic change, such as urbanization, can lead to loss
      of fitness when animals use behavioral strategies intended to maximize fitness in
      natural landscapes. 

PMID- 23979681
TI  - Pregnancy in women with gliomas: a case-series and review of the literature.
AB  - The occurrence of pregnancy in women with brain tumors confronts both patients
      and physicians with difficult decision making at each stage of pregnancy. We
      studied the course of events of nine pregnancies in seven women with low-grade
      glioma in our hospital over a 10 year period. Five patients had a surgical
      resection, one a biopsy and one woman was followed by wait-and-see policy before
      pregnancy. In two women, a therapeutic abortion was carried out in the first
      trimester because of signs of progression, necessitating surgical removal of the
      tumor. In the other five women pregnancy had an uncomplicated course. Based on a
      literature review, we found 28 women diagnosed with a known glioma before
      becoming pregnant. All pregnancies but one, were uneventful and all women had a
      normal delivery, including the seven cases with exposure to chemotherapy and in
      whom healthy babies were born. A total of 75 pregnant women were identified in
      whom new onset glioma developed, which was high-grade in 56 %, and becoming
      symptomatic in 51 % during the third trimester, usually by focal neurological
      deficits. We conclude that in relation to pregnancy, low-grade gliomas are more
      often seen in women already known with a brain tumor, while high-grade gliomas
      represent more frequently a new onset phenomenon. Based on these observations,
      guidelines are given on initiation of antitumor therapy during pregnancy, seizure
      management, counseling on therapeutic abortion, and on the timing and choice of
      obstetrical interventions.

PMID- 23979682
TI  - Glioblastoma management in the temozolomide era: have we improved outcome?
AB  - Temozolomide (TMZ) during and after radiotherapy (RT) is recommended for patients
      with newly diagnosed glioblastoma (GBM). We analyzed the adoption of this new
      standard of care for GBM in an academic cancer centre in Canada and assessed its
      impact on survival. GBM patients registered with Cancer Care Ontario between 2004
      and 2008 were identified. Those >= 16 years age, newly diagnosed, treated at our
      institution, had confirmed pathology and complete records were included.
      Demographics, treatments, toxicity and outcome were captured. For survival
      analysis patients were stratified by age, ECOG, and treatment modalities
      including total cycles of TMZ. Descriptive statistics were used for early
      progressors and long term survivors. Kaplan-Meier curves, log-rank test and Cox
      proportional hazards model were used for survival analyses. At a median follow-up
      of 28 months, we compared our outcome to updated EORTC-NCIC CE 3 results. Of 517
      patients 433 were included for analysis. Majority were male (63 %), ECOG 0-1 (66
      %), and <= 65 years (55 %). 44 % received CRT followed by TMZ, 13 % had CRT only,
      30 % had RT only and 13 % had best supportive care. 10 % were early progressors
      and 9 % survived beyond 2 years. Comparison of our results to NCIC CTG CE.3 study
      data showed median survival was 15.8 versus 14.6 months, 2 year survival rate for
      CRT plus TMZ was 35 versus 26 %, and for RT alone 0 versus 10 %, respectively.
      <50 % of GBM patients complete CRT with TMZ in the real-world setting. Prognosis
      for most patients with GBM remains dismal particularly if they are not suitable
      for RT and CRT.

PMID- 23979683
TI  - Gliomas of the posterior fossa in adults.
AB  - Infratentorial gliomas are relatively rare tumors compared to their
      supratentorial counterparts. As such they have not been extensively characterized
      as a group and are usually excluded from clinical studies. Using our database we
      aimed to characterize adult gliomas involving the posterior fossa with respect to
      their clinical behavior and prognostic factors. We reviewed our neurosurgical and
      neuro-oncological data bases for adult patients diagnosed with gliomas involving
      the posterior fossa between 1996 and 2010. Of 1,283 glioma patients, 57 patients
      with gliomas involving the posterior fossa were identified (4.4 %). Tumors were
      further classified by location as primary brainstem (n = 21) and primary
      cerebellar (n = 18) tumors. On univariate analysis survival was correlated to
      tumor grade and KPS. In addition we have identified a unique group of patients (n
      = 18) with previously diagnosed supratentorial gliomas who subsequently developed
      noncontiguous secondary infratentorial extension of their tumors with subsequent
      rapid clinical deterioration. Gliomas of the posterior fossa comprise a
      heterogeneous group of tumors. Histological grade of the tumor was found to be
      the main prognostic factor. Survival of primary cerebellar gliomas is comparable
      to supra-tentorial gliomas, while brainstem gliomas in adults fare better than in
      the pediatric population. Secondary extension of supratentorial gliomas to the
      posterior fossa signifies a grave prognosis.

PMID- 23979685
TI  - Recurrent hypoglycemia from insulin autoimmune syndrome.
AB  - Insulin autoimmune syndrome (IAS) is an uncommon cause of hyperinsulinemic
      hypoglycemia characterized by autoantibodies to endogenous insulin in individuals
      without previous exposure to exogenous insulin. IAS is the third leading cause of
      spontaneous hypoglycemia in Japan, and is increasingly being recognized worldwide
      in non-Asian populations. We report a case of IAS in a Caucasian woman with
      recurrent complaints of hypoglycemia, with laboratory findings of serum glucose
      2.5 mmol/L (45 mg/dL), insulin 54,930 pmol/L (7,909 MUIU/mL), connecting peptide
      (C-peptide) 4,104 pmol/L (12.4 ng/mL), and a corresponding insulin to C-peptide
      molar ratio of 13.4 during a spontaneous hypoglycemic event. Autoantibodies to
      insulin were markedly elevated at > 50 kU/L (> 50 U/mL). IAS should be considered
      in the differential diagnosis of hypoglycemia in non-diabetic individuals.
      Distinction from insulinoma is especially crucial to prevent unwarranted invasive
      procedures and surgical interventions in hypoglycemic patients.

PMID- 23979686
TI  - Translating research into practice: the colorectal cancer screening experience.

PMID- 23979684
TI  - Racial/ethnic differences in trust in health care: HIV conspiracy beliefs and
      vaccine research participation.
AB  - BACKGROUND: Prior research has documented a high prevalence of conspiracy beliefs
      about the origin of the human immunodeficiency virus (HIV) and the role of the
      government in the acquired immunodeficiency syndrome (AIDS) epidemic,
      particularly among racial and ethnic minorities in the United States. Whether
      such beliefs are a barrier to participation in HIV prevention research is not
      known. OBJECTIVE: To understand the prevalence of HIV conspiracy beliefs and
      their relationship to willingness to participate in HIV vaccine research among
      three racial/ethnic groups. DESIGN: Cross-sectional survey. PARTICIPANTS: Six
      hundred and one community-recruited volunteers (33.0 % White, 32.5 % Mexican
      American, and 34.5 % African American). MAIN MEASURES: We evaluated the level of
      agreement with six previously described HIV conspiracy beliefs, trust in medical
      research, and willingness to participate in HIV vaccine research. Multivariate
      models were used to compare these parameters among the three racial/ethnic groups
      while controlling for the potential confounding effects of socioeconomic status,
      access to health care, and other demographic factors. RESULTS: African Americans,
      Mexican Americans, and whites had similar levels of distrust in medical research.
      African and Mexican Americans were more likely to endorse one or more of six HIV
      conspiracy beliefs than whites (59.0 % and 58.6 % versus 38.9 %, respectively, P
      < 0.001), but were significantly more willing to participate in HIV vaccine
      research (ORs 1.58, CI 1.10-2.25 and 2.53, CI 1.75-3.66, respectively). Among
      respondents of all racial/ethnic groups, endorsing HIV conspiracy beliefs was not
      associated with willingness to participate in research. CONCLUSIONS: HIV
      conspiracy beliefs, while common among all racial and ethnic groups in the United
      States, do not preclude willingness to participate in HIV prevention research.

PMID- 23979687
TI  - The superiority of patient engagement and shared decision-making in
      noninferiority trials.

PMID- 23979689
TI  - Selective fluorescence sensing of Cu(II) and Zn(II) using a new Schiff base
      derived model compound: naked eye detection and spectral deciphering of the
      mechanism of sensory action.
AB  - A new Schiff base compound 2-((benzylimino)-methyl)-naphthalen-1-ol (2BIMN1O) has
      been synthesized and characterized by (1)H NMR, (13)C NMR, DEPT, FT-IR and mass
      spectroscopic techniques. The significantly low fluorescence yield of the
      compound has been rationalized in connection with photo-induced electron transfer
      (PET) from the imine receptor moiety to the naphthalene fluorophore unit.
      Subsequently, an evaluation of the transition metal ion-induced modification of
      the fluorophore-receptor communication reveals a promising prospect for the title
      compound to function as a fluorosensor for Cu(2+) and Zn(2+) ions selectively,
      through remarkable fluorescence enhancement. While perturbation of the PET
      process in 2BIMN1O has been argued to be the responsible mechanism behind the
      fluorescence enhancement, the selectivity for these two metal ions has been
      interpreted on the grounds of an appreciably strong binding interaction.
      Particularly notable aspects regarding the chemosensory activity of the compound
      are its ability to detect the aforesaid transition metal ions down to the level
      of micromolar concentration (detection limit being 0.82 and 0.35 MUM
      respectively), along with a simple and efficient synthetic procedure. Also the
      spectral modulation of 2BIMN1O in the presence of the transition metal ions paves
      the way for the construction of a calibration curve in the context of its
      fluorescence signaling potential. 

PMID- 23979688
TI  - Hydroxysafflor yellow A improves learning and memory in a rat model of vascular
      dementia by increasing VEGF and NR1 in the hippocampus.
AB  - Hydroxysafflor yellow A (HSYA) has angiogenesis-regulating and neuro-protective
      effects, but its effects on vascular dementia (VaD) are unknown. In this study,
      30 adult Sprague-Dawley rats were randomly allocated to five groups: normal, sham
      operation, VaD alone (bilateral carotid artery occlusion), VaD plus saline
      (control), and VaD plus HSYA. One week after operation, the HSYA group received
      one daily tail-vein injection of 0.6 mg/100 g HSYA for two weeks. Five weeks
      after operation, the spatial memory of all five groups was evaluated by the water
      maze task, and synaptic plasticity in the hippocampus was assessed by the long
      term potentiation (LTP) method. Vascular endothelial growth factor (VEGF) and N
      methyl-Daspartic acid receptor 1 (NR1) expression in the hippocampus was detected
      via Western blot. We found that, compared with the group with VaD alone, the
      group with HSYA had a reduced escape latency in the water maze (P < 0.05), and
      the LTP at CA3-CA1 synapses in the hippocampus was enhanced (P < 0.05). Western
      blot in the late-phase VaD group showed slight up-regulation of VEGF and
      downregulation of NR1 in the hippocampus, while HSYA significantly up-regulated
      both VEGF and NR1. These results suggested that HSYA promotes angiogenesis and
      increases synaptic plasticity, thus improving spatial learning and memory in the
      rat model of VaD.

PMID- 23979690
TI  - Suppression of Th1 cytokine production by a peptide derived from C4b.
AB  - OBJECTIVES: The complement system has been proposed to play a significant role in
      the regulation of T-cell responses. However, the precise mechanism underlying C4
      induced immune tolerance remains to be clarified. We recently reported that
      monomeric C4b inhibits CXCL10 production from blood cells. The purpose of this
      study was to verify the active site of monomeric C4b. MATERIALS AND METHODS: We
      investigated the in vitro effects of a C4b-derived peptide (VPAGSARPVAFSVVPTAAA),
      named HP2 (highly homologous peptide 2), on the IFN-beta-induced production of
      CXCL10 in human blood and the in vivo effects of the administration of HP2 on
      Th1/2 cytokine production in the spleen in mice. We also tested whether the
      administration of HP2 influences symptoms of experimentally induced ulcerative
      colitis in mice. RESULTS: HP2 inhibited CXCL10 production in human blood, and the
      administration of HP2 significantly suppressed the production of Th1 cytokines,
      such as IL-2, IFN-gamma, and TNF-alpha, in spleen cells isolated from mice. The
      administration of HP2 in the mice significantly improved the symptoms of colitis,
      with down-regulation of colitogenic CD4(+)CD45RB(high) T cells and up-regulation
      of CD4(+)LAP/TGF-beta1(+) T cells. CONCLUSION: The amino acid sequence described
      above is suggested to be the active site in C4b for the inhibition of Th1
      cytokine production. These results should contribute to the development of new
      drugs suppressing autoimmune responses.

PMID- 23979691
TI  - Therapeutic potential of biodegradable microparticles containing Punica granatum
      L. (pomegranate) in murine model of asthma.
AB  - OBJECTIVE AND DESIGN: Among the options for treatment of diseases affecting the
      respiratory system, especially asthma, drug delivering systems for intranasal
      application represent an important therapeutic approach at the site of
      inflammation. The present study aimed to evaluate the therapeutic effect of
      biodegradable microparticles formed by poly lactic-co-glycolic acid (PLGA)
      containing encapsulated pomegranate extract on a murine model of asthma.
      MATERIAL: The extract was acquired from the leaves of P. granatum and
      characterized qualitatively by HPLC. A w/o/w emulsion solvent extraction
      evaporation method was chosen to prepare the microparticles containing
      pomegranate encapsulated extract (MP). TREATMENT: OVA-sensitized BALB/c mice were
      used as asthma model and treated with dexamethasone and P. granatum extract in
      solution form or encapsulated into microparticles. RESULTS: MP were able to
      inhibit leukocytes' recruitment to bronchoalveolar fluid, especially,
      eosinophils, decreasing cytokines (IL-1beta and IL-5) and protein levels in the
      lungs. CONCLUSIONS: This approach can be used as an alternative/supplementary
      therapy based on the biological effects of P. granatum for managing inflammatory
      processes, especially those with pulmonary complications.

PMID- 23979692
TI  - Pericentrin expression in Down's syndrome.
AB  - Down's syndrome (DS) is the most frequent genetic cause of intellectual
      disability and is a chromosomal abnormality of chromosome 21 trisomy. The
      pericentrin gene (PCNT) has sequenced in 21q22.3 inside of the minimal critical
      region for Down's syndrome. Alterations of PCNT gene are associated with
      dwarfism, cardiomyopathy and other pathologies. In this study, we have evaluated
      the possible differential expression of PCNT mRNA, by qRT-PCR, in peripheral
      blood leukocytes of DS subjects compared with the normal population. In the
      present case-control study, PCNT gene expression was increased by 72.72% in 16
      out 22 DS samples compared with normal subjects. Our data suggest that changes in
      the expression levels of PCNT in DS subjects may be involved into the molecular
      mechanism of Down's syndrome.

PMID- 23979693
TI  - Modified direct anterior approach in minimally invasive hip hemiarthroplasty in a
      geriatric population: a feasibility study and description of the technique.
AB  - INTRODUCTION: The direct anterior approach (DAA) is generally accepted method for
      minimal invasive arthroplasty of the hip. As good results for total hip
      arthroplasty are already published, there is a lack of evidence for the
      implantation of bipolar hip hemiarthroplasty (BHH) in elderly patients with
      osteoporosis after femoral neck fracture. MATERIALS AND METHODS: For hip
      arthroplasty using a direct anterior approach (DAA) in elderly patients with
      femoral neck fractures, a number of modifications of the original technique are
      being described. The modified DAA considers in particular the co-morbidity and
      the bone quality of the geriatric patient population. A consecutive series of 16
      hemiarthroplasties using this technique is presented. In all 16 cases, the BHH
      was implanted in modified DAA technique. Mobility measured by 4-item Barthel
      Index, pain via visual analogue scale (VAS), duration of surgery, external length
      of incision and blood loss were evaluated. RESULTS: There was no major operative
      complication during the procedures. The pain level decreased from 7
      (preoperatively) to 0 at postoperative day 40. The Barthel Index increased from 5
      at first postoperative day to 40 at day 40. Early postoperative mobilisation is
      efficiently accelerated. Mean operating time was 71 min; the medium skin incision
      length was 8 cm. The mean haemoglobin level decreased from 118 g/dl
      preoperatively to 101 g/dl at first postoperative day. CONCLUSION: The described
      modifications of the DAA help to implant a BHH gently in elderly patients with
      increasing risk of complications like iatrogenic fractures, wound or prosthesis
      infections and haematoma. This will hopefully lead to a faster rehabilitation and
      lower mortality rate for patients with femoral neck fractures in the future.

PMID- 23979694
TI  - A Perspective on HRT for Women: Picking Up the Pieces After The Women's Health
      Initiative Trial-Part 1.

PMID- 23979695
TI  - Patient Satisfaction With Pharmacist Intervention and Consultation in HRT.

PMID- 23979696
TI  - Sensitization therapy for warts.

PMID- 23979697
TI  - Effectiveness in Oral Rhus toxicodendron Solution for Poison Ivy.

PMID- 23979698
TI  - HIPAA Privacy and Security for Providers: The Basics.

PMID- 23979699
TI  - Containment of hazardous particulates in the compounding pharmacy.

PMID- 23979700
TI  - Basics of Compounding for Raynaud's Disease.

PMID- 23979701
TI  - Quality-control analytical methods: viscosity measurements.

PMID- 23979702
TI  - Chemical stability of cefuroxime sodium after reconstitution in 0.9% sodium
      chloride injection and storage in polypropylene syringes for pediatric use.
AB  - The stability of cefuroxime sodium (50mg/mL) in 0.9% sodium chloride injection
      stored in polypropylene syringes was studied at 25 and 5 deg C by means of a
      stability-indicating high-performance liquid chromatographic assay method. The
      concentrations of the drug were directly related to peak heights, and the percent
      relative standard deviation based on five injections was 0.9. There were at least
      two products of decomposition that separated from the intact drug. The loss in
      potency was less than 10% after 2 days of storage at 25 deg C, and the loss in
      potency was less than 4% after 21 days of storage at 5 deg C. The pH vallue
      increased from 6.9 to 7.3 when the injection was stored at 25 deg C for 2 days,
      and the pH value increased from 6.9 to 7.0 when the injection was stored at 5 deg
      C for 21 days. The drug was not adsorbed onto the syringes. The intensity of the
      light-yellow color increased with the storage period at 25 deg C, but did not
      change signiificantly with storage at 5 deg C. 

PMID- 23979703
TI  - Stability of hydralazine hydrochloride in both flavored and non- flavored
      extemporaneous preparations.
AB  - The objective of this study was to evaluate the chemical stability of hydralazine
      hydrochloride 0.1% and 1% when prepared extemporaneously from commercially
      available hydralazine bulk powder. The oral solutions were prepared to contain
      preservatives, sweeteners, a humectant and diluting agents. They were prepared
      flavored and nonflavored and stored in duplicate glass and plastic bottles. Each
      of the flavored preparations was stored at 5 deg C, 25 deg C/60% relative
      humidity and 40 deg C/75% relative humdidity. Samples from the bottles of
      concentrations stored under these conditions were taken for a period of up to 92
      days. Each of the nonflavored preparations was stored at 5 deg C. Samples from
      the bottles stored under these conditions were taken for a period of up to 72
      days. Samples were taken from glass and plastic bottles on the designated
      sampling days for both flavored and nonflavored preparations, and the samples
      were analyzed for drug concentration using a stability-indicating high-pressure
      liquid chromatography analyical technique. Degradation occurred faster in the
      0.1% oral solution than in the 1% solution at all the studied conditions. At 40
      deg C, a considerable amount of drug loss was observed for both the 0.1 % and the
      1% oral solutions for the flavored preparations. For both flavored and
      nonflavored preparations, the lowest studied temperature condition (5 deg C)
      appeared to be the most favorable for the preparations, with 93% or more of the
      initial potency retained by day 29. 

PMID- 23979704
TI  - A novel dRYBP-SCF complex functions to inhibit apoptosis in Drosophila.
AB  - A balanced response to intrinsic and extrinsic apoptotic signals is crucial to
      support homeostatic development and animal survival. Regulation of activation and
      inhibition of apoptotic pathways involves diverse mechanisms including protein
      ubiquitylation to control expression levels of apoptotic factors. Here we report
      that drosophila Ring and YY1 Binding Protein (dRYBP) protein interacts both
      genetically and biochemically with the E3 ubiquitin ligase SKPA, dCULLIN, F-box
      (SCF) complex to synergistically inhibit apoptosis in Drosophila. Further, we
      show that the loss of skpA function activates the intrinsic pathway of apoptosis
      and down-regulates the levels of expression of the anti-apoptotic DIAP1 protein.
      Accordingly, the apoptosis induced by inactivation of skpA and dRYBP is rescued
      by loss of function of the pro-apoptotic gene reaper and overexpression of DIAP1.
      Of interest, we also find that high levels of SKPA protein rescue the wing
      phenotype induced by overexpression of Reaper protein. Finally, we demonstrate
      that overexpression of SKPA inhibits both developmental and radiation-induced
      apoptosis. We propose that the function of the dRYBP-SCF complex in the
      inhibition of apoptosis might possibly be to control the levels of the pro
      apoptotic and anti-apoptotic proteins most likely by promoting their
      ubiquitylation and consequently, proteasomal degradation. Given the evolutionary
      conservation of the dRYBP and the SCF proteins, our results suggest that their
      mammalian homologs may function in balancing cell survival versus cell death
      during normal and pathological development. 

PMID- 23979705
TI  - Microglia-mediated neuroinflammation is an amplifier of virus-induced
      neuropathology.
AB  - Microglia, the major resident immune cells in the central nervous system (CNS)
      are considered as the key cellular mediators of neuroinflammatory processes. In
      the past few years, microglial research has become a main focus in cellular
      neuroimmunology and neuroinflammation. Chronic/remitting neurological disease
      such as multiple sclerosis (MS) has long been considered an inflammatory
      autoimmune disease with the infiltration of peripheral myelin-specific T cells
      into the CNS. With the rapid advancement in the field of microglia and astrocytic
      neurobiology, the term neuroinflammation progressively started to denote chronic
      CNS cell-specific inflammation in MS. The direct glial responses in MS are
      different from conventional peripheral immune responses. This review attempts to
      summarize current findings of neuroinflammatory responses within the CNS by
      direct infection of neural cells by mouse hepatitis virus (MHV) and the
      mechanisms by which glial cell responses ultimately contribute to the
      neuropathology on demyelination. Microglia can be persistently infected by MHV.
      Microglial activation and phagocytosis are recognized to be critically important
      in the pathogenesis of demyelination. Emerging evidence for the pathogenic role
      of microglia and the activation of inflammatory pathways in these cells in MHV
      infection supports the concept that microglia induced neuroinflammation is an
      amplifier of virus-induced neuropathology. 

PMID- 23979706
TI  - Matrix metalloproteinase levels in early HIV infection and relation to in vivo
      brain status.
AB  - Matrix metalloproteinases (MMPs) have been implicated in human immunodeficiency
      virus (HIV)-associated neurological injury; however, this relationship has not
      been studied early in infection. Plasma levels of MMP-1, MMP-2, MMP-7, MMP-9, and
      MMP-10 measured using Luminex technology (Austin, TX, USA) were compared in 52
      HIV and 21 seronegative participants of the Chicago Early HIV Infection study.
      MMP levels were also examined in HIV subgroups defined by antibody reactivity,
      viremia, and antiretroviral status, as well as in available cerebrospinal fluid
      (CSF) samples (n = 9). MMPs were evaluated for patterns of relationship to
      cognitive function and to quantitative magnetic resonance measurements of the
      brain derived in vivo. Plasma MMP-2 levels were significantly reduced in early
      HIV infection and correlated with altered white matter integrity and atrophic
      brain changes. MMP-9 levels were higher in the treated subgroup than in the naive
      HIV subgroup. Only MMP-2 and MMP-9 were detected in the CSF; CSF MMP-2 correlated
      with white matter integrity and with volumetric changes in basal ganglia.
      Relationships with cognitive function were also identified. MMP-2 levels in
      plasma and in CSF correspond to early changes in brain structure and function.
      These findings establish a link between MMPs and neurological status previously
      unidentified in early HIV infection. 

PMID- 23979707
TI  - SILAC-based proteomics of human primary endothelial cell morphogenesis unveils
      tumor angiogenic markers.
AB  - Proteomics has been successfully used for cell culture on dishes, but more
      complex cellular systems have proven to be challenging and so far poorly
      approached with proteomics. Because of the complexity of the angiogenic program,
      we still do not have a complete understanding of the molecular mechanisms
      involved in this process, and there have been no in depth quantitative proteomic
      studies. Plating endothelial cells on matrigel recapitulates aspects of vessel
      growth, and here we investigate this mechanism by using a spike-in SILAC
      quantitative proteomic approach. By comparing proteomic changes in primary human
      endothelial cells morphogenesis on matrigel to general adhesion mechanisms in
      cells spreading on culture dish, we pinpoint pathways and proteins modulated by
      endothelial cells. The cell-extracellular matrix adhesion proteome depends on the
      adhesion substrate, and a detailed proteomic profile of the extracellular matrix
      secreted by endothelial cells identified CLEC14A as a matrix component, which
      binds to MMRN2. We verify deregulated levels of these proteins during tumor
      angiogenesis in models of multistage carcinogenesis. This is the most in depth
      quantitative proteomic study of endothelial cell morphogenesis, which shows the
      potential of applying high accuracy quantitative proteomics to in vitro models of
      vessel growth to shed new light on mechanisms that accompany pathological
      angiogenesis. The mass spectrometry proteomics data have been deposited to the
      ProteomeXchange Consortium with the data set identifier PXD000359. 

PMID- 23979708
TI  - Ion-current-based proteomic profiling of the retina in a rat model of Smith-Lemli
      Opitz syndrome.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is one of the most common recessive human
      disorders and is characterized by multiple congenital malformations as well as
      neurosensory and cognitive abnormalities. A rat model of SLOS has been developed
      that exhibits progressive retinal degeneration and visual dysfunction; however,
      the molecular events underlying the degeneration and dysfunction remain poorly
      understood. Here, we employed a well-controlled, ion-current-based approach to
      compare retinas from the SLOS rat model to retinas from age- and sex-matched
      control rats (n = 5/group). Retinas were subjected to detergent extraction and
      subsequent precipitation and on-pellet-digestion procedures and then were
      analyzed on a long, heated column (75 cm, with small particles) with a 7-h
      gradient. The high analytical reproducibility of the overall proteomics procedure
      enabled reliable expression profiling. In total, 1,259 unique protein groups,
      ~40% of which were membrane proteins, were quantified under highly stringent
      criteria, including a peptide false discovery rate of 0.4%, with high quality ion
      current data (e.g. signal-to-noise ratio >= 10) obtained independently from at
      least two unique peptides for each protein. The ion-current-based strategy showed
      greater quantitative accuracy and reproducibility over a parallel spectral
      counting analysis. Statistically significant alterations of 101 proteins were
      observed; these proteins are implicated in a variety of biological processes,
      including lipid metabolism, oxidative stress, cell death, proteolysis, visual
      transduction, and vesicular/membrane transport, consistent with the features of
      the associated retinal degeneration in the SLOS model. Selected targets were
      further validated by Western blot analysis and correlative immunohistochemistry.
      Importantly, although photoreceptor cell death was validated by TUNEL analysis,
      Western blot and immunohistochemical analyses suggested a caspase-3-independent
      pathway. In total, these results provide compelling new evidence implicating
      molecular changes beyond the initial defect in cholesterol biosynthesis in this
      retinal degeneration model, and they might have broader implications with respect
      to the pathobiological mechanism underlying SLOS.

PMID- 23979709
TI  - The multiple chemokine-binding bovine herpesvirus 1 glycoprotein G (BHV1gG)
      inhibits polymorphonuclear cell but not monocyte migration into inflammatory
      sites.
AB  - Chemokines facilitate the recruitment of inflammatory cells into tissues,
      contributing to target organ injury in a wide range of inflammatory and
      autoimmune diseases. Targeting either single chemokines or chemokine receptors
      alters the progression of disease in animal models of rheumatoid arthritis and
      lupus with varying degrees of efficacy but clinical trials in humans have been
      less successful. Given the redundancy of chemokine-chemokine receptor
      interactions, targeting of more than one chemokine may be required to inhibit
      active inflammatory disease. To test the effects of multiple-chemokine blockade
      in inflammation, we generated an adenovirus expressing bovine herpesvirus 1
      glycoprotein G (BHV1gG), a viral chemokine antagonist that binds to a wide
      spectrum of murine and human chemokines, fused to the Fc portion of murine IgG2a.
      Administration of the adenovirus significantly inhibited thioglycollate-induced
      migration of polymorphonuclear leukocytes into the peritoneal cavity of BALB/c
      mice and reduced both clinical severity and articular damage in K/BxN serum
      transfer-induced arthritis. However, treatment with BHV1gG-Ig fusion protein did
      not prevent monocyte infiltration into the peritoneum in the thioglycollate model
      and did not prevent renal monocyte infiltration or nephritis in lupus-prone NZB/W
      mice. These observations suggest that the simultaneous inhibition of multiple
      chemokines by BHV1gG has the potential to interfere with acute inflammatory
      responses mediated by polymorphonuclear leukocytes, but is less effective in
      chronic inflammatory disease mediated by macrophages. 

PMID- 23979710
TI  - Influence of microsatellite instability and KRAS and BRAF mutations on lymph node
      harvest in stage I-III colon cancers.
AB  - Lymph node (LN) harvest is influenced by several factors, including tumor
      genetics. Microsatellite instability (MSI) is associated with improved node
      harvest, but the association to other genetic factors is largely unknown.
      Research methods included a prospective series of stage I-III colon cancer
      patients undergoing ex vivo sentinel-node sampling. The presence of MSI, KRAS
      mutations in codons 12 and 13, and BRAF V600E mutations was analyzed. Uni- and
      multivariate regression models for node sampling were adjusted for clinical,
      pathological and molecular features. Of 204 patients, 67% had an adequate harvest
      (>= 12 nodes). Adequate harvest was highest in patients whose tumors exhibited
      MSI (79%; odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2-4.9; P = 0.007)
      or were located in the proximal colon (73%; 2.8, 1.5-5.3; P = 0.002). In multiple
      linear regression, MSI was a significant predictor of the total LN count (P =
      0.02). Total node count was highest for cancers with MSI and no KRAS/BRAF
      mutations. The independent association between MSI and a high LN count persisted
      for stage I and II cancers (P = 0.04). Tumor location in the proximal colon was
      the only significant predictor of an adequate LN harvest (adjusted OR 2.4, 95% CI
      1.2-4.9; P = 0.01). An increase in the total number of nodes harvested was not
      associated with an increase in nodal metastasis. In conclusion, number of nodes
      harvested is highest for cancers of the proximal colon and with MSI. The nodal
      harvest associated with MSI is influenced by BRAF and KRAS genotypes, even for
      cancers of proximal location. Mechanisms behind the molecular diversity and node
      yield should be further explored.

PMID- 23979713
TI  - Frequency of infectious diseases in immigrants in a Western European country: a
      population-based study.
AB  - The aim of this population-based study was to assess the incidence rates of
      infectious diseases in native- (Italian) and foreign-born (immigrants)
      populations in a North Italy area, in 2006-2010. Crude, age-specific incidence
      rates (IRs) and age-standardised rate ratios (SRRs) between foreign- and native
      born subjects and their 95% confidence intervals (95% CI) were estimated. A total
      of 32,554 cases of infectious diseases were found (9.9% in foreign-born
      subjects). The highest SRRs between foreign- and nativeborn subjects were found
      for tuberculosis (SRR = 27.1; 95% CI 21.3-34.3), malaria (SRR = 21.1; 14.6-30.4),
      scabies (SRR = 8.5; 7.6-9.4), AIDS (SRR = 2.5; 1.8-3.4) and viral hepatitis B
      (SRR = 3.3; 2.1-5.2). The highest IR was found for AIDS in people from the
      Americas (IR = 4.57; 95% CI 2.2-8.4), for malaria and tuberculosis in people from
      Africa (IR = 13.89; 11.6-16.5 and IR = 11.87; 9.8-14.3 respectively). Therefore
      immigrants are at a higher risk of acquiring some common infectious diseases
      compared to the native population in Western European countries.

PMID- 23979711
TI  - Genetic enhancement of Brassica napus seed quality.
AB  - The ultimate value of the Brassica napus (canola) seed is derived from the oil
      fraction, which has long been recognized for its premium dietary attributes,
      including its low level of saturated fatty acids, high content of monounsaturated
      fatty acids, and favorable omega-3 fatty acid profile. However, the protein
      (meal) portion of the seed has also received favorable attention for its
      essential amino acids, including abundance of sulfur-containing amino acids, such
      that B. napus protein is being contemplated for large scale use in livestock and
      fish feed formulations. Efforts to optimize the composition of B. napus oil and
      protein fractions are well documented; therefore, this article will review
      research concerned with optimizing secondary metabolites that affect the quality
      of seed oil and meal, from undesirable anti-nutritional factors to highl value
      beneficial products. The biological, agronomic, and economic values attributed to
      secondary metabolites have brought much needed attention to those in Brassica
      oilseeds and other crops. This review focuses on increasing levels of beneficial
      endogenous secondary metabolites (such as carotenoids, choline and tochopherols)
      and decreasing undesirable antinutritional factors (glucosinolates, sinapine and
      phytate). Molecular genetic approaches are given emphasis relative to classical
      breeding. 

PMID- 23979714
TI  - Perceived stigma of purchasing sex among Latino and non-Latino male clients of
      female sex workers in Tijuana, Mexico.
AB  - HIV prevention efforts must be comprehensive in their understanding of the
      factors involved in HIV risk. Male clients, who have received less research
      attention than female sex workers (FSWs), may experience stigma as a function of
      purchasing sex. Perceived stigma may be related to poor psychological outcomes,
      risky psychosexual characteristics, and higher drug and sexual risk behavior
      among male clients of FSWs. However, perceived stigma of purchasing sex may
      differ between clients of different ethnic groups. In the present study, we
      examine the correlates of perceived stigma of purchasing sex among Latino versus
      non-Latino male clients of FSWs in Tijuana, Mexico. Using time-location sampling,
      we recruited 375 male clients (323 Latino, 52 non-Latino) in Tijuana who
      completed a computerized survey on various measures. We measured perceived stigma
      of purchasing sex using three items we developed for this study. Using linear
      regression analyses we found that perceived stigma was associated with greater
      guilt, a greater feeling of escape from everyday life, and more negative condom
      attitudes among Latino clients. This was not found among non-Latino clients.
      Features of Latino culture, like machismo, and how they may relate to stigma of
      purchasing sex are discussed. 

PMID- 23979715
TI  - Drebrin contains a cryptic F-actin-bundling activity regulated by Cdk5
      phosphorylation.
AB  - Drebrin is an actin filament (F-actin)-binding protein with crucial roles in
      neuritogenesis and synaptic plasticity. Drebrin couples dynamic microtubules to F
      actin in growth cone filopodia via binding to the microtubule-binding +TIP
      protein EB3 and organizes F-actin in dendritic spines. Precisely how drebrin
      interacts with F-actin and how this is regulated is unknown. We used cellular and
      in vitro assays with a library of drebrin deletion constructs to map F-actin
      binding sites. We discovered two domains in the N-terminal half of drebrin-a
      coiled-coil domain and a helical domain-that independently bound to F-actin and
      cooperatively bundled F-actin. However, this activity was repressed by an
      intramolecular interaction relieved by Cdk5 phosphorylation of serine 142 located
      in the coiled-coil domain. Phospho-mimetic and phospho-dead mutants of serine 142
      interfered with neuritogenesis and coupling of microtubules to F-actin in growth
      cone filopodia. These findings show that drebrin contains a cryptic F-actin
      bundling activity regulated by phosphorylation and provide a mechanistic model
      for microtubule-F-actin coupling. 

PMID- 23979716
TI  - Spindle assembly checkpoint proteins are positioned close to core microtubule
      attachment sites at kinetochores.
AB  - Spindle assembly checkpoint proteins have been thought to reside in the
      peripheral corona region of the kinetochore, distal to microtubule attachment
      sites at the outer plate. However, recent biochemical evidence indicates that
      checkpoint proteins are closely linked to the core kinetochore microtubule
      attachment site comprised of the Knl1-Mis12-Ndc80 (KMN) complexes/KMN network. In
      this paper, we show that the Knl1-Zwint1 complex is required to recruit the Rod
      Zwilch-Zw10 (RZZ) and Mad1-Mad2 complexes to the outer kinetochore. Consistent
      with this, nanometer-scale mapping indicates that RZZ, Mad1-Mad2, and the C
      terminus of the dynein recruitment factor Spindly are closely juxtaposed with the
      KMN network in metaphase cells when their dissociation is blocked and the
      checkpoint is active. In contrast, the N terminus of Spindly is ~75 nm outside
      the calponin homology domain of the Ndc80 complex. These results reveal how
      checkpoint proteins are integrated within the substructure of the kinetochore and
      will aid in understanding the coordination of microtubule attachment and
      checkpoint signaling during chromosome segregation. 

PMID- 23979717
TI  - Distinct signaling mechanisms regulate migration in unconfined versus confined
      spaces.
AB  - Using a microchannel assay, we demonstrate that cells adopt distinct signaling
      strategies to modulate cell migration in different physical microenvironments. We
      studied alpha4beta1 integrin-mediated signaling, which regulates cell migration
      pertinent to embryonic development, leukocyte trafficking, and melanoma invasion.
      We show that alpha4beta1 integrin promotes cell migration through both unconfined
      and confined spaces. However, unlike unconfined (2D) migration, which depends on
      enhanced Rac1 activity achieved by preventing alpha4/paxillin binding, confined
      migration requires myosin II-driven contractility, which is increased when Rac1
      is inhibited by alpha4/paxillin binding. This Rac1-myosin II cross talk mechanism
      also controls migration of fibroblast-like cells lacking alpha4beta1 integrin, in
      which Rac1 and myosin II modulate unconfined and confined migration,
      respectively. We further demonstrate the distinct roles of myosin II isoforms,
      MIIA and MIIB, which are primarily required for confined and unconfined
      migration, respectively. This work provides a paradigm for the plasticity of
      cells migrating through different physical microenvironments. 

PMID- 23979721
TI  - Novel mixed-valence Cu compounds formed by Cu(II) dimers with double oximato
      bridges: in situ formation of anionic layer [Cu2(SCN)3]n(n-).
AB  - Two new N3O donor ketoxime Schiff bases (HL(1) and HL(2)) have been synthesized
      by condensing N,N-dimethylethylenediamine with diacetylmonoxime and
      benzilmonoxime, respectively in a 1:1 ratio. Reaction of Cu(ClO4)2.6H2O with
      HL(1) resulted in a discrete oximato-bridged dinuclear Cu(II) complex
      [Cu2(L(1))2(H2O)2](ClO4)2 (1). The same reaction in presence of NaSCN affords the
      complex {[Cu(II)2(L(1))2][Cu(I)4(MU(1,3)-SCN)4(MU(1,1,3)-SCN)2]}n (2), where
      partial Cu(II)->Cu(I) reduction is observed. In 2, arrays of [Cu(II)2(L(1))2](2+)
      cationic units are inserted in between 2D {[Cu(I)4(SCN)6](2-)}n layers and
      connected via MU(1,1,3)-SCN(-) links, thus forming a 3D network. On the other
      hand, reaction of Cu(CH3COO)2 and HL(2) in the presence of NaSCN gave rise to a
      mixed-valence pentanuclear cluster {[Cu(II)2(L(2))2(NCS)]2[Cu(I)(SCN)(MU(1,1)
      SCN)(MU(1,3)-SCN)]} (3) where Cu(II) is also partly reduced to Cu(I). In compound
      3, two cationic [Cu(II)2(L(2))2(NCS)](+) units are bridged by the anionic
      [Cu(I)(SCN)3](2-) unit through long Cu-SCN linkages. The ligands and the
      complexes have been characterized by elemental analysis, UV/Vis and IR
      spectroscopy. The complexes are further characterized by single crystal X-ray
      diffraction and variable temperature magnetic (VTM) studies. Finally a complete
      magneto-structural correlation has been established between compounds 1-3 and all
      the characterized Cu dimers with a double NO bridge.

PMID- 23979719
TI  - Centrosome repositioning in T cells is biphasic and driven by microtubule end-on
      capture-shrinkage.
AB  - T cells rapidly reposition their centrosome to the center of the immunological
      synapse (IS) to drive polarized secretion in the direction of the bound target
      cell. Using an optical trap for spatial and temporal control over target
      presentation, we show that centrosome repositioning in Jurkat T cells exhibited
      kinetically distinct polarization and docking phases and required calcium flux
      and signaling through both the T cell receptor and integrin to be robust. In
      "frustrated" conjugates where the centrosome is stuck behind the nucleus, the
      center of the IS invaginated dramatically to approach the centrosome.
      Consistently, imaging of microtubules during normal repositioning revealed a
      microtubule end-on capture-shrinkage mechanism operating at the center of the IS.
      In agreement with this mechanism, centrosome repositioning was impaired by
      inhibiting microtubule depolymerization or dynein. We conclude that dynein drives
      centrosome repositioning in T cells via microtubule end-on capture-shrinkage
      operating at the center of the IS and not cortical sliding at the IS periphery,
      as previously thought. 

PMID- 23979718
TI  - JNK-mediated phosphorylation of DLK suppresses its ubiquitination to promote
      neuronal apoptosis.
AB  - Neurons are highly polarized cells that often project axons a considerable
      distance. To respond to axonal damage, neurons must transmit a retrograde signal
      to the nucleus to enable a transcriptional stress response. Here we describe a
      mechanism by which this signal is propagated through injury-induced stabilization
      of dual leucine zipper-bearing kinase (DLK/MAP3K12). After neuronal insult,
      specific sites throughout the length of DLK underwent phosphorylation by c-Jun N
      terminal kinases (JNKs), which have been shown to be downstream targets of DLK
      pathway activity. These phosphorylation events resulted in increased DLK
      abundance via reduction of DLK ubiquitination, which was mediated by the E3
      ubiquitin ligase PHR1 and the de-ubiquitinating enzyme USP9X. Abundance of DLK in
      turn controlled the levels of downstream JNK signaling and apoptosis. Through
      this feedback mechanism, the ubiquitin-proteasome system is able to provide an
      additional layer of regulation of retrograde stress signaling to generate a
      global cellular response to localized external insults. 

PMID- 23979722
TI  - Swim bladder function and buoyancy control in pink snapper (Pagrus auratus) and
      mulloway (Argyrosomus japonicus).
AB  - Physoclist fish are able to regulate their buoyancy by secreting gas into their
      hydrostatic organ, the swim bladder, as they descend through the water column and
      by resorbing gas from their swim bladder as they ascend. Physoclists are
      restricted in their vertical movements due to increases in swim bladder gas
      volume that occur as a result of a reduction in hydrostatic pressure, causing
      fish to become positively buoyant and risking swim bladder rupture. Buoyancy
      control, rates of swim bladder gas exchange and restrictions to vertical
      movements are little understood in marine teleosts. We used custom-built
      hyperbaric chambers and laboratory experiments to examine these aspects of
      physiology for two important fishing target species in southern Australia, pink
      snapper (Pagrus auratus) and mulloway (Argyrosomus japonicus). The swim bladders
      of pink snapper and mulloway averaged 4.2 and 4.9 % of their total body volumes,
      respectively. The density of pink snapper was not significantly different to the
      density of seawater (1.026 g/ml), whereas mulloway were significantly denser than
      seawater. Pink snapper secreted gas into their swim bladders at a rate of 0.027
      +/- 0.005 ml/kg/min (mean +/- SE), almost 4 times faster than mulloway (0.007 +/-
      0.001 ml/kg/min). Rates of swim bladder gas resorption were 11 and 6 times faster
      than the rates of gas secretion for pink snapper and mulloway, respectively. Pink
      snapper resorbed swim bladder gas at a rate of 0.309 +/- 0.069 ml/kg/min, 7 times
      faster than mulloway (0.044 +/- 0.009 ml/kg/min). Rates of gas exchange were not
      affected by water pressure or water temperature over the ranges examined in
      either species. Pink snapper were able to acclimate to changes in hydrostatic
      pressure reasonably quickly when compared to other marine teleosts, taking
      approximately 27 h to refill their swim bladders from empty. Mulloway were able
      to acclimate at a much slower rate, taking approximately 99 h to refill their
      swim bladders. We estimated that the swim bladders of pink snapper and mulloway
      ruptured after decreases in ~2.5 and 2.75 times the hydrostatic pressure to which
      the fish were acclimated, respectively. Differences in buoyancy, gas exchange
      rates, limitations to vertical movements and acclimation times between the two
      species are discussed in terms of their differing behaviour and ecology.

PMID- 23979723
TI  - Suicide versus self-inflicted: is it time to change manner of death
      classification?

PMID- 23979724
TI  - Dynamic optimization identifies optimal programmes for pathway regulation in
      prokaryotes.
AB  - To survive in fluctuating environmental conditions, microorganisms must be able
      to quickly react to environmental challenges by upregulating the expression of
      genes encoding metabolic pathways. Here we show that protein abundance and
      protein synthesis capacity are key factors that determine the optimal strategy
      for the activation of a metabolic pathway. If protein abundance relative to
      protein synthesis capacity increases, the strategies shift from the simultaneous
      activation of all enzymes to the sequential activation of groups of enzymes and
      finally to a sequential activation of individual enzymes along the pathway. In
      the case of pathways with large differences in protein abundance, even more
      complex pathway activation strategies with a delayed activation of low abundance
      enzymes and an accelerated activation of high abundance enzymes are optimal. We
      confirm the existence of these pathway activation strategies as well as their
      dependence on our proposed constraints for a large number of metabolic pathways
      in several hundred prokaryotes. 

PMID- 23979725
TI  - Algorithm for the management of femoral shaft fractures in children.
AB  - PURPOSE: Pediatric closed femoral shaft fractures are commonly related to a good
      prognosis. There is no consensus on treatment. We aimed to evaluate the
      treatment, features, radiological findings and management strategies, creating an
      algorithm of treatment. MATERIALS AND METHODS: Fifty-two simple femoral shaft
      fractures in children were retrospectively evaluated for age and gender
      distribution, side of the fracture, etiology of injuries, limb length
      discrepancy, range of knee and hip motion and parents satisfaction with a mean
      clinical and radiographic follow-up of 3 years and 6 months. Twenty-eight
      patients were treated with reduction and early hip spica cast while 24 patients
      were treated with external fixation (EF). RESULTS: Nearly 58 % of the cases were
      caused by traffic accidents and were predominantly male (61.5 %). Most of the
      fractures were of the middle femoral shaft (57.6 %). Muscle strength was normal
      (MRC scale) in all patients with no pain (NIPS and PRS scale). Knee and Hip range
      of motion were similar in both types of treatment. Patients treated with EF had
      shorter limb length discrepancy compared with SC. There were no reports of re
      fracture. We found a higher familiar satisfaction in patients treated with EF.
      CONCLUSIONS: An algorithm for the management of femoral shaft fractures in the
      pediatric population is proposed. Results on the study population gave raise to a
      satisfactory clinical and radiological results.

PMID- 23979726
TI  - Decreased expression and role of GRK6 in spinal cord of rats after chronic
      constriction injury.
AB  - Nerve injury and inflammation can both induce neuropathic pain via the production
      of pro-inflammatory cytokines. In the process, G protein-coupled receptors
      (GPCRs) were involved in pain signal transduction. GPCR kinase (GRK) 6 is a
      member of the GRK family that regulates agonist-induced desensitization and
      signaling of GPCRs. However, its expression and function in neuropathic pain have
      not been reported. In this study, we performed a chronic constriction injury
      (CCI) model in adult male rats and investigated the dynamic change of GRK6
      expression in spinal cord. GRK6 was predominantly expressed in the superficial
      layers of the lumbar spinal cord dorsal horn neurons and its expression was
      decreased bilaterally following induction of CCI. The changes of GRK6 were mainly
      in IB4 and P substrate positive areas in spinal cord dorsal horn. And over
      expression of GRK6 in spinal cord by lentivirus intrathecal injection attenuated
      the pain response induced by CCI. In addition, the level of TNF-alpha underwent
      the negative pattern of GRK6 in spinal cord. And neutralized TNF-alpha by
      antibody intrathecal injection up-regulated GRK6 expression and attenuated the
      mechanical allodynia and heat hyperalgesia in CCI model. All the data indicated
      that down-regulation of neuronal GRK6 expression induced by cytokine may be a
      potential mechanism that contributes to increasing neuronal signaling in
      neuropathic pain. 

PMID- 23979728
TI  - High pressure nanoelectrospray ionization mass spectrometry for analysis of
      aqueous solutions.
AB  - Nanoelectrospray ionization (nanoESI) with a very fine emitter and nanoliter
      solution flow rate is known to be suitable for aqueous solutions. However, under
      atmospheric pressure, its stability with aqueous solutions is not always
      guaranteed particularly in the negative ion mode where corona and arc discharge
      tend to occur more easily. Electrical discharge can be quenched to a certain
      extent by adding electron scavenging gases like SF6 or CO2 to the ion source. The
      onset potential that is required to induce the discharge also increases with an
      increase of gas pressure. Recently, we have reported on a series of high pressure
      electrospray ion sources that were stable in both positive and negative ion modes
      using air or N2 as the working gas. In this paper, we compare the performance of
      nanoelectrospray under atmospheric pressure and super-atmospheric pressure for
      the analysis of samples in aqueous solution. The comparative study was performed
      using the same ion source chamber that could be pressurized up to 6 bar. The
      pressure in the first pumping stage of the mass spectrometer was kept constant
      when the ion source pressure was changed by using an additional pump with
      variable pumping speed. High pressure nanoESI optimized at 2-3 bar demonstrated a
      3-5 times improvement in ion signal intensity compared to atmospheric pressure
      nanoESI, and the signal stability was significantly improved particularly in the
      negative mode. 

PMID- 23979727
TI  - Melatonin protects against diazinon-induced neurobehavioral changes in rats.
AB  - Diazinon is an organophosphorous pesticide with a prominent toxicity on many body
      organs. Multiple mechanisms contribute to diazinon-induced deleterious effects.
      Inhibition of acetyl-cholinesterase, cholinergic hyperstimulation, and formation
      of reactive oxygen species may play a role. On the other hand, melatonin is a
      pineal hormone with a well-known potent antioxidant activity and a remarkable
      modulatory effect on many behavioral processes. The present study revealed that
      oral diazinon administration (25 mg/kg) increased anxiety behavior in rats
      subjected to elevated plus maze and open-field tests possibly via the induction
      of changes in brain monoamines levels (dopamine, norepinephrine, and serotonin).
      Additionally, brain lipid peroxides measured as malondialdehyde (MDA) and tumor
      necrosis factor alpha (TNF-alpha) levels were elevated, while the activity of
      brain glutathione peroxidase enzyme was reduced by diazinon. Co-administration of
      oral melatonin (10 mg/kg) significantly attenuated the anxiogenic activity of
      diazinon, rebalanced brain monoamines levels, decreased brain MDA and TNF-alpha
      levels, and increased the activity of brain glutathione peroxidase enzyme.

PMID- 23979729
TI  - Treatment outcomes for Mycobacterium avium complex: a systematic review and meta
      analysis.
AB  - To evaluate the existing evidence regarding treatment regimens for Mycobacterium
      avium complex (MAC), a systematic review of the available therapeutic studies was
      conducted to assess treatment outcomes. A random-effects meta-analysis was used
      to assess treatment outcomes. Subgroup analyses were also conducted by separating
      studies based on each characteristic independently. Twenty-eight trials met the
      inclusion criteria. Our meta-analysis showed that the estimated pooled treatment
      success rate for patients with MAC disease was 39 % [95 % confidence interval
      (CI) 38-41 %]. The rates of failure, relapse, death, and default were 27 % (95 %
      CI 25-29 %), 6 % (95 % CI 5-7 %), 17 % (95 % CI 15-18 %), and 12 % (95 % CI 11-13
      %), respectively. The proportion of patients treated successfully did not differ
      significantly on the basis of the study characteristics. However, studies with
      treatment regimens containing macrolides had significantly higher pooled success
      proportions (42 %, 95 % CI 40-44 %) than that of other studies (28 %, 95 % CI 24
      32 %). Substantial heterogeneity in the study characteristics prevented more
      conclusive determination of what factors had the greatest effect on the
      proportion of patients that achieve treatment success and limited the validity of
      this analysis. This review underscored the importance of strong patient support
      and treatment follow-up systems to develop successful MAC treatment programs.

PMID- 23979730
TI  - Iatrogenic Cushing's syndrome induced by posaconazole.
AB  - Iatrogenic Cushing's syndrome is an undesirable outcome of glucocorticoids
      treatment. It can be increased by pharmacologic interactions. Glucocorticoid
      therapy, given in association with ritonavir, and some azole treatments are
      causes of iatrogenic Cushing's syndrome. We present a patient with common
      variable immunodeficiency who received 7 years of itraconazole therapy for
      bronchial colonization with Aspergillus in combination with inhaled fluticasone
      without any Cushingoid symptoms. After a switch to posaconazole, the patient
      developed Cushingoid symptoms. 

PMID- 23979732
TI  - In vitro cross-resistance profile of nucleoside reverse transcriptase inhibitor
      (NRTI) BMS-986001 against known NRTI resistance mutations.
AB  - BMS-986001 is a novel HIV nucleoside reverse transcriptase inhibitor (NRTI). To
      date, little is known about its resistance profile. In order to examine the cross
      resistance profile of BMS-986001 to NRTI mutations, a replicating virus system
      was used to examine specific amino acid mutations known to confer resistance to
      various NRTIs. In addition, reverse transcriptases from 19 clinical isolates with
      various NRTI mutations were examined in the Monogram PhenoSense HIV assay. In the
      site-directed mutagenesis studies, a virus containing a K65R substitution
      exhibited a 0.4-fold change in 50% effective concentration (EC50) versus the wild
      type, while the majority of viruses with the Q151M constellation (without M184V)
      exhibited changes in EC50 versus wild type of 0.23- to 0.48-fold. Susceptibility
      to BMS-986001 was also maintained in an L74V-containing virus (0.7-fold change),
      while an M184V-only-containing virus induced a 2- to 3-fold decrease in
      susceptibility. Increasing numbers of thymidine analog mutation pattern 1 (TAM-1)
      pathway mutations correlated with decreases in susceptibility to BMS-986001,
      while viruses with TAM-2 pathway mutations exhibited a 5- to 8-fold decrease in
      susceptibility, regardless of the number of TAMs. A 22-fold decrease in
      susceptibility to BMS-986001 was observed in a site-directed mutant containing
      the T69 insertion complex. Common non-NRTI (NNRTI) mutations had little impact on
      susceptibility to BMS-986001. The results from the site-directed mutants
      correlated well with the more complicated genotypes found in NRTI-resistant
      clinical isolates. Data from clinical studies are needed to determine the
      clinically relevant resistance cutoff values for BMS-986001. 

PMID- 23979731
TI  - Evaluation of intravenous anthrax immune globulin for treatment of inhalation
      anthrax.
AB  - Bacillus anthracis toxins can be neutralized by antibodies against protective
      antigen (PA), a component of anthrax toxins. Anthrivig (human anthrax
      immunoglobulin), also known as AIGIV, derived from plasma of humans immunized
      with BioThrax (anthrax vaccine adsorbed), is under development for the treatment
      of toxemia following exposure to anthrax spores. The pharmacokinetics (PK) of
      AIGIV was assessed in naive animals and healthy human volunteers, and the
      efficacy of AIGIV was assessed in animals exposed via inhalation to aerosolized
      B. anthracis spores. In the clinical study, safety, tolerability, and PK were
      evaluated in three dose cohorts (3.5, 7.1, and 14.2 mg/kg of body weight of anti
      PA IgG) with 30 volunteers per cohort. The elimination half-life of AIGIV in
      rabbits, nonhuman primates (NHPs), and humans following intravenous infusion was
      estimated to be approximately 4, 12, and 24 days, respectively, and dose
      proportionality was observed. In a time-based treatment study, AIGIV protected 89
      to 100% of animals when administered 12 h postexposure; however, a lower survival
      rate of 39% was observed when animals were treated 24 h postexposure,
      underscoring the need for early intervention. In a separate set of studies,
      animals were treated on an individual basis upon detection of a clinical sign or
      biomarker of disease, namely, a significant increase in body temperature (SIBT)
      in rabbits and presence of PA in the serum of NHPs. In these trigger-based
      intervention studies, AIGIV induced up to 75% survival in rabbits depending on
      the dose and severity of toxemia at the time of treatment. In NHPs, up to 33%
      survival was observed in AIGIV-treated animals. (The clinical study has been
      registered at ClinicalTrials.gov under registration no. NCT00845650.). 

PMID- 23979733
TI  - Lack of pharmacokinetic interaction between rilpivirine and integrase inhibitors
      dolutegravir and GSK1265744.
AB  - Dolutegravir (DTG) and GSK1265744 are HIV integrase inhibitors (INIs) in clinical
      development. The oral formulation of rilpivirine (RPV), a nonnucleoside reverse
      transcriptase inhibitor (NNRTI), has been approved for treatment-naive HIV
      infection. Long-acting depot injections of GSK1265744 and RPV are also being
      developed. This study evaluated the potential for drug interactions between RPV
      and these INIs. This phase 1, open-label, two-cohort, three-period, single
      sequence crossover study evaluated oral coadministration of RPV with DTG or
      GSK1265744. Healthy subjects received DTG (50 mg every 24 h for 5 days) or
      GSK1265744 (30 mg every 24 h for 12 days) in period 1 followed by a washout, RPV
      (25 mg every 24 h for 11 or 12 days) in period 2, immediately followed by RPV (25
      mg every 24 h) plus DTG (50 mg every 24 h) for 5 days or GSK1265744 (30 mg every
      24 h) for 12 days in period 3. Steady-state pharmacokinetic (PK) parameters were
      estimated using noncompartmental analysis of data collected on the last day of
      each period. The combinations of RPV and DTG (n = 16) and of RPV and GSK1265744
      (n = 11) were well tolerated; no grade 3 or 4 adverse events (AEs) or AE-related
      discontinuations were observed. The 90% confidence intervals for the area under
      the curve from time zero until the end of the dosage interval [AUC0-tau] and
      maximum concentration of drug in serum (Cmax) geometric mean ratios were within
      0.8 to 1.25. Following administration of DTG + RPV, DTG and RPV Ctau increased by
      22% and 21%, respectively. Following administration of GSK1265744 + RPV, RPV Ctau
      decreased 8%. DTG and GSK1265744 can be administered with RPV without dosage
      adjustment for either agent. These results support coadministration of RPV with
      DTG or GSK1265744 as either oral or long-acting depot injection regimens. (This
      study has been registered at ClinicalTrials.gov under registration no.
      NCT01467531.). 

PMID- 23979734
TI  - Staphylococcus aureus fatty acid auxotrophs do not proliferate in mice.
AB  - Inactivation of acetyl-coenzyme A (acetyl-CoA) carboxylase confers resistance to
      fatty acid synthesis inhibitors in Staphylococcus aureus on media supplemented
      with fatty acids. The addition of anteiso-fatty acids (1 mM) plus lipoic acid
      supports normal growth of DeltaaccD strains, but supplementation with mammalian
      fatty acids was less efficient. Mice infected with strain RN6930 developed
      bacteremia, but bacteria were not detected in mice infected with its DeltaaccD
      derivative. S. aureus bacteria lacking acetyl-CoA carboxylase can be propagated
      in vitro but were unable to proliferate in mice, suggesting that the acquisition
      of inactivating mutations in this enzyme is not a mechanism for the evasion of
      fatty acid synthesis inhibitors. 

PMID- 23979735
TI  - Novel pseudo-staphylococcal cassette chromosome mec element (psiSCCmec57395) in
      methicillin-resistant Staphylococcus pseudintermedius CC45.
AB  - Genetic characterization of methicillin-resistant Staphylococcus pseudintermedius
      (MRSP) from Thailand and Israel revealed the presence of a predominant atypical
      clonal lineage which was not typeable by SmaI-PFGE and SCCmec typing. All the
      atypical isolates (n = 34) belonged to CC45 (30 ST45 and 2 ST179 isolates, 1 ST57
      isolate, and 1 ST85 isolate). The isolates originated from healthy and diseased
      dogs and cats, as well as from the environment of one clinic. Cfr9I-pulsed-field
      gel electrophoresis (Cfr9I-PFGE) and dru typing permitted the further distinction
      of CC45 isolates from the two different countries. Microarray analysis identified
      genes that confer resistance to beta-lactams (mecA; blaZ), aminoglycosides
      [aac(6')-Ie-aph(2')-Ia; aph(3')-III; ant(6)-Ia], macrolides and lincosamides
      [erm(B)], tetracyclines [tet(M)], trimethoprim [dfr(G)], streptothricin (sat4),
      and chloramphenicol (catpC221). Fluoroquinolone resistance was attributed to
      specific amino acid substitutions, i.e., Ser84Leu in GyrA and Ser80Ile and
      Asp84Asn in GrlA. A novel pseudo-staphylococcal cassette chromosome
      (PsiSCCmec57395) element was identified in MRSP strain 57395 (sequence type ST45)
      by whole-genome sequencing. The 12,282-bp PsiSCCmec57395 element contained a
      class C1 mec gene complex but no ccr genes. In addition to the methicillin
      resistance gene mecA, PsiSCCmec57395 also carried determinants of resistance to
      heavy metals, such as arsenic, cadmium, and copper. Bsu36I restriction analysis
      of the PsiSCCmec57395 element amplified by long-range PCR revealed the presence
      of PsiSCCmec57395 in the 33 additional isolates of MRSP CC45. The PsiSCCmec57395
      element represents a new class of SCCmec and has been identified in MRSP of CC45,
      which is a predominant clonal lineage in Israel and Thailand. 

PMID- 23979736
TI  - Homeostasis of glutathione is associated with polyamine-mediated beta-lactam
      susceptibility in Acinetobacter baumannii ATCC 19606.
AB  - Glutathione is a tripeptide (l-gamma-glutamyl-l-cysteinyl-glycine) thiol compound
      existing in many bacteria and maintains a proper cellular redox state, thus
      protecting cells against toxic substances such as reactive oxygen species.
      Polyamines (spermine and spermidine) are low-molecular-weight aliphatic
      polycations ubiquitously presenting in all living cells and modulate many
      cellular functions. We previously reported that exogenous polyamines
      significantly enhanced beta-lactam susceptibility of beta-lactam-associated
      multidrug-resistant Acinetobacter baumannii. In this study, three genes
      differentially associated with the polyamine effects on beta-lactam
      susceptibility were identified by transposon mutagenesis of A. baumannii ATCC
      19606. All three genes encoded components of membrane transport systems.
      Inactivation of one of the genes encoding a putative glutathione transport ATP
      binding protein increased the accumulation of intracellular glutathione (~150 to
      ~200%) and significantly decreased the polyamine effects on beta-lactam
      susceptibility in A. baumannii ATCC 19606. When the cells were grown with
      polyamines, the levels of intracellular glutathione in A. baumannii ATCC 19606
      significantly decreased from ~0.5 to ~0.2 nmol, while the levels of extracellular
      glutathione were correspondingly increased. However, the levels of total
      glutathione (intra- plus extracellular) were unchanged when the cells were grown
      with or without polyamines. Overall, these results suggest that exogenous
      polyamines induce glutathione export, resulting in decreased levels of
      intracellular glutathione, which may produce an improper cellular redox state
      that is associated with the polyamine-mediated beta-lactam susceptibility of A.
      baumannii. This finding may provide a clue for development of new antimicrobial
      agents and/or novel strategies to treat multidrug-resistant A. baumannii. 

PMID- 23979737
TI  - Effect of a high-calorie, high-fat meal on the bioavailability and
      pharmacokinetics of PA-824 in healthy adult subjects.
AB  - PA-824 is a novel nitroimidazo-oxazine being developed as an antituberculosis
      agent. Two randomized studies evaluated the pharmacokinetics and safety of a
      single oral dose of PA-824 administered to healthy adult subjects 30 min after a
      high-calorie, high-fat meal (fed state) versus after a minimum 10-h fast (fasted
      state). A total of 48 subjects were dosed in the two studies in a randomized
      crossover design with PA-824 at dose levels of 50, 200, or 1,000 mg in the fed
      state or fasted state. After the administration of PA-824, the geometric mean
      ratios of Cmax and AUC0-infinity revealed an increase in exposure with the
      addition of a high-calorie, high-fat meal compared to the fasted state by 140 and
      145% at 50 mg, 176 and 188% at 200 mg, and 450 and 473% at 50, 200, and 1,000 mg,
      respectively. The median Tmax in the fed state was 4 h for the 50-mg dose and 5 h
      for the 200- and 1,000-mg doses. In the fasted state, the median Tmax was 4 h for
      the 50- and 200-mg doses and 6.5 h for the 1,000-mg dose. All doses were well
      tolerated, and no serious adverse events occurred in either study. (This study
      has been registered at ClinicalTrials.gov under registration numbers NCT01828827
      and NCT01830439.). 

PMID- 23979738
TI  - Mutational analysis of quinolone resistance protein QnrB1.
AB  - Alanine substitutions and selected deletions have been used to localize amino
      acids in QnrB essential for its protective activity. Essential amino acids are
      found at positions i and i(-2) in the pentapeptide repeat module and in the
      larger of two loops, where deletion of only a single amino acid compromises
      activity. Deletion of 10 amino acids at the N terminus is tolerated, but removal
      of 3 amino acids in the C-terminal dimerization unit destroys activity. 

PMID- 23979739
TI  - In vivo emergence of colistin resistance in Klebsiella pneumoniae producing KPC
      type carbapenemases mediated by insertional inactivation of the PhoQ/PhoP mgrB
      regulator.
AB  - Colistin is one of the few agents that retain activity against extensively drug
      resistant strains of Klebsiella pneumoniae producing KPC-type carbapenemases (KPC
      KP). However, resistance to colistin is increasingly reported among KPC-KP.
      Comparative genomic analysis of a pair of sequential KPC-KP isolates from the
      same patient including a colistin-susceptible isolate (KKBO-1) and a colistin
      resistant isolate (KKBO-4) selected after colistin exposure revealed that
      insertional inactivation of the mgrB gene, encoding a negative regulator of the
      PhoQ/PhoP signaling system, is a genetic mechanism for acquired colistin
      resistance. The role of mgrB inactivation in acquired colistin resistance was
      confirmed by complementation experiments with wild-type mgrB, which restored
      colistin susceptibility in KKBO-4, and by construction of an mgrB deletion mutant
      from KKBO-1, which exhibited a colistin-resistant phenotype. Insertional mgrB
      inactivation was also detected in 60% of colistin-resistant mutants selected from
      KKBO-1 in vitro, following plating on colistin-containing medium, confirming the
      role (although not unique) of this mechanism in the emergence of acquired
      colistin resistance. In colistin-resistant mutants carrying insertional
      inactivation or deletion of the mgrB gene, upregulated transcription of phoP,
      phoQ, and pmrK (which is part of the pmrHFIJKLM operon) was detected. These
      findings confirmed the MgrB regulatory role in K. pneumoniae and were in
      agreement with the known association between upregulation of the PhoQ/PhoP system
      and activation of the pmrHFIJKLM operon, which eventually leads to resistance to
      polymyxins by modification of the lipopolysaccharide target. 

PMID- 23979740
TI  - Effect of anthrax immune globulin on response to BioThrax (anthrax vaccine
      adsorbed) in New Zealand white rabbits.
AB  - Development of anthrax countermeasures that may be used concomitantly in a
      postexposure setting requires an understanding of the interaction between these
      products. Anthrax immune globulin intravenous (AIGIV) is a candidate
      immunotherapeutic that contains neutralizing antibodies against protective
      antigen (PA), a component of anthrax toxins. We evaluated the interaction between
      AIGIV and BioThrax (anthrax vaccine adsorbed) in rabbits. While pharmacokinetics
      of AIGIV were not altered by vaccination, the vaccine-induced immune response was
      abrogated in AIGIV-treated animals. 

PMID- 23979741
TI  - Impact of reduced vancomycin MIC on clinical outcomes of methicillin-resistant
      Staphylococcus aureus bacteremia.
AB  - Vancomycin has been a key antibiotic agent for the treatment of methicillin
      resistant Staphylococcus aureus (MRSA) infections. However, little is known about
      the relationship between vancomycin MIC values at the higher end of the
      susceptibility range and clinical outcomes. The aim of this study was to
      determine the impact of MRSA bacteremia on clinical outcomes in patients with a
      vancomycin MIC near the upper limit of the susceptible range. Patients with MRSA
      bacteremia were divided into a high-vancomycin-MIC group (2 MUg/ml) and a low
      vancomycin-MIC group (<=1.0 MUg/ml). We examined the relationship between MIC,
      genotype, primary source of bacteremia, and mortality. Ninety-four patients with
      MRSA bacteremia, including 31 with a high vancomycin MIC and 63 with a low MIC
      were analyzed. There was no significant difference between the presence of agr
      dysfunction and SCCmec type between the two groups. A higher vancomycin MIC was
      not found to be associated with mortality. In contrast, high-risk bloodstream
      infection sources (hazard ratio [HR], 4.63; 95% confidence interval [CI] = 1.24
      to 17.33) and bacterial eradication after treatment (HR, 0.06; 95% CI = 0.02 to
      0.17), irrespective of vancomycin MIC, were predictors of all-cause 30-day
      mortality. Our study suggests that a high-risk source of bacteremia is likely to
      be associated with unfavorable clinical outcomes, but a high vancomycin MIC in a
      susceptible range, as well as genotype characteristics, are not associated with
      mortality. 

PMID- 23979742
TI  - New structure of phage-related islands carrying fusB and a virulence gene in
      fusidic acid-resistant Staphylococcus epidermidis.
AB  - Nucleotide sequencing of the fusB-flanking regions in two fusidic acid-resistant
      Staphylococcus epidermidis isolates with the type IV aj1-leader peptide (LP)-fusB
      structure (lacking aj1) revealed that their fusB gene was located on novel phage
      related islands inserted downstream of smpB and are here referred to as SeRIfusB
      3692 and SePIfusB-857. The novel SePIfusB-857 structure was followed by SeCI857,
      forming a composite pathogenicity island which contained a putative virulence
      gene, vapE. The linkage of fusB and vapE may contribute to bacterial adaption. 

PMID- 23979743
TI  - Isolation of genetically indistinguishable carbapenem-resistant and -susceptible
      Acinetobacter baumannii isolates from a single patient.

PMID- 23979744
TI  - Biological markers of Pseudomonas aeruginosa epidemic high-risk clones.
AB  - A limited number of Pseudomonas aeruginosa genotypes (mainly ST-111, ST-175, and
      ST-235), known as high-risk clones, are responsible for epidemics of nosocomial
      infections by multidrug-resistant (MDR) or extensively drug-resistant (XDR)
      strains worldwide. We explored the potential biological parameters that may
      explain the success of these clones. A total of 20 isolates from each of 4
      resistance groups (XDR, MDR, ModR [resistant to 1 or 2 classes], and MultiS
      [susceptible to all antipseudomonals]), recovered from a multicenter study of P.
      aeruginosa bloodstream infections performed in 10 Spanish hospitals, were
      analyzed. A further set of 20 XDR isolates belonging to epidemic high-risk clones
      (ST-175 [n = 6], ST-111 [n = 7], and ST-235 [n = 7]) recovered from different
      geographical locations was also studied. When unknown, genotypes were documented
      through multilocus sequence typing. The biological parameters evaluated included
      twitching, swimming, and swarming motility, biofilm formation, production of
      pyoverdine and pyocyanin, spontaneous mutant frequencies, and the in vitro
      competition index (CI) obtained with a flow cytometry assay. All 20 (100%) XDR, 8
      (40%) MDR, and 1 (5%) ModR bloodstream isolate from the multicenter study
      belonged to high-risk clones. No significant differences were observed between
      clonally diverse ModR and MultiS isolates for any of the parameters. In contrast,
      MDR/XDR high-risk clones showed significantly increased biofilm formation and
      mutant frequencies but significantly reduced motility (twitching, swimming, and
      swarming), production of pyoverdine and pyocyanin, and fitness. The defined
      biological markers of high-risk clones, which resemble those resulting from
      adaptation to chronic infections, could be useful for the design of specific
      treatment and infection control strategies. 

PMID- 23979745
TI  - Nested case-control study of the emergence of tigecycline resistance in multidrug
      resistant Klebsiella pneumoniae.
AB  - We performed a nested case-control study (ratio of 1:4) on the emergence of
      tigecycline-resistant multidrug-resistant Klebsiella pneumoniae (TR-MDRKP)
      isolates among patients who initially presented with a tigecycline-susceptible
      MDRKP isolate. Out of 260 patients, 24 (9%) had a subsequent clinical culture
      positive for a TR-MDRKP isolate within the 90-day follow-up period. On logistic
      regression analyses, receipt of tigecycline (adjusted odds ratio [OR], 5.06; 95%
      confidence interval [CI], 1.80 to 14.23; P = 0.002) was the only independent
      predictor of subsequent isolation of a TR strain. 

PMID- 23979746
TI  - Plasma concentrations of isoniazid and rifampin are decreased in adult pulmonary
      tuberculosis patients with diabetes mellitus.
AB  - Plasma isoniazid and rifampin concentrations, but not pyrazinamide and ethambutol
      concentrations, were decreased by about 50% (P < 0.05) in diabetic pulmonary
      tuberculosis patients. The prevalences of subnormal plasma isoniazid, rifampin,
      pyrazinamide, and ethambutol concentrations were 49% or 100% (P < 0.01), 66% or
      100% (P < 0.05), 30% or 50% (P = 0.198), and 32% or 21% (P = 0.742) in
      nondiabetic or diabetic tuberculosis patients, respectively. These data show that
      plasma concentrations of isoniazid and rifampin were greatly reduced in diabetic
      tuberculosis patients. 

PMID- 23979747
TI  - In vitro effects of novel ruthenium complexes in Neospora caninum and Toxoplasma
      gondii tachyzoites.
AB  - Upon the screening of 16 antiproliferative compounds against Toxoplasma gondii
      and Neospora caninum, two hydrolytically stable ruthenium complexes (compounds 16
      and 18) exhibited 50% inhibitory concentrations of 18.7 and 41.1 nM (T. gondii)
      and 6.7 and 11.3 nM (N. caninum). To achieve parasiticidal activity with compound
      16, long-term treatment (22 to 27 days at 80 to 160 nM) was required.
      Transmission electron microscopy demonstrated the rapid impact on and
      ultrastructural alterations in both parasites. These preliminary findings suggest
      that the potential of ruthenium-based compounds should thus be further exploited.

PMID- 23979748
TI  - Effects of bacteriocins on methicillin-resistant Staphylococcus aureus biofilm.
AB  - Control of biofilms formed by microbial pathogens is an important subject for
      medical researchers, since the development of biofilms on foreign-body surfaces
      often causes biofilm-associated infections in patients with indwelling medical
      devices. The present study examined the effects of different kinds of
      bacteriocins, which are ribosomally synthesized antimicrobial peptides produced
      by certain bacteria, on biofilms formed by a clinical isolate of methicillin
      resistant Staphylococcus aureus (MRSA). The activities and modes of action of
      three bacteriocins with different structures (nisin A, lacticin Q, and nukacin
      ISK-1) were evaluated. Vancomycin, a glycopeptide antibiotic used in the
      treatment of MRSA infections, showed bactericidal activity against planktonic
      cells but not against biofilm cells. Among the tested bacteriocins, nisin A
      showed the highest bactericidal activity against both planktonic cells and
      biofilm cells. Lacticin Q also showed bactericidal activity against both
      planktonic cells and biofilm cells, but its activity against biofilm cells was
      significantly lower than that of nisin A. Nukacin ISK-1 showed bacteriostatic
      activity against planktonic cells and did not show bactericidal activity against
      biofilm cells. Mode-of-action studies indicated that pore formation leading to
      ATP efflux is important for the bactericidal activity against biofilm cells. Our
      results suggest that bacteriocins that form stable pores on biofilm cells are
      highly potent for the treatment of MRSA biofilm infections. 

PMID- 23979749
TI  - High-level pacidamycin resistance in Pseudomonas aeruginosa is mediated by an opp
      oligopeptide permease encoded by the opp-fabI operon.
AB  - Pacidamycins (or uridyl peptide antibiotics) possess selective in vivo activity
      against Pseudomonas aeruginosa. An important limitation for the therapeutic use
      of pacidamycins with P. aeruginosa is the high frequency (10(-6) to 10(-7)) at
      which resistant mutants emerge. To elucidate the mechanism(s) of this resistance,
      pacidamycin-resistant P. aeruginosa mutants were isolated. Two types of mutants
      were obtained. Type 1, or high-level resistance mutants with a pacidamycin MIC of
      512 MUg/ml, were more abundant, with a frequency of~2 * 10(-6), and did not show
      cross-resistance with other antibiotics. Type 2, low-level resistance mutants,
      were isolated with a frequency of ~10(-8) and had a pacidamycin MIC of 64 MUg/ml
      (the MIC for the wild-type strain was 4 to 16 MUg/ml). These mutants were cross
      resistant to levofloxacin, tetracycline, and erythromycin and were shown to
      overexpress either the MexAB-OprM or MexCD-OprJ multidrug resistance efflux
      pumps. High-level resistant mutants were isolated by transposon mutagenesis and
      one insertion was localized to oppB, one of two periplasmic binding protein
      components of an oligopeptide transport system which is encoded by the opp-fabI
      operon. The Opp system is required for uptake of pacidamycin across the inner
      membrane, since various opp, but not fabI, mutants were resistant to high levels
      of pacidamycin. Both of the two putative Opp periplasmic binding proteins, OppA
      and OppB, were required for pacidamycin uptake. Although both impaired uptake
      into and efflux from the cell can cause pacidamycin resistance in P. aeruginosa,
      our data suggest that impaired uptake is the primary reason for the high
      frequency and high-level pacidamycin resistance.

PMID- 23979750
TI  - Antibacterial activity of eravacycline (TP-434), a novel fluorocycline, against
      hospital and community pathogens.
AB  - Eravacycline (TP-434 or 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6
      deoxytetracycline) is a novel fluorocycline that was evaluated for antimicrobial
      activity against panels of recently isolated aerobic and anaerobic Gram-negative
      and Gram-positive bacteria. Eravacycline showed potent broad-spectrum activity
      against 90% of the isolates (MIC90) in each panel at concentrations ranging from
      <=0.008 to 2 MUg/ml for all species panels except those of Pseudomonas aeruginosa
      and Burkholderia cenocepacia (MIC90 values of 32 MUg/ml for both organisms). The
      antibacterial activity of eravacycline was minimally affected by expression of
      tetracycline-specific efflux and ribosomal protection mechanisms in clinical
      isolates. Furthermore, eravacycline was active against multidrug-resistant
      bacteria, including those expressing extended-spectrum beta-lactamases and
      mechanisms conferring resistance to other classes of antibiotics, including
      carbapenem resistance. Eravacycline has the potential to be a promising new
      intravenous (i.v.)/oral antibiotic for the empirical treatment of complicated
      hospital/health care infections and moderate-to-severe community-acquired
      infections. 

PMID- 23979751
TI  - Transdermal glyceryl trinitrate as an effective adjunctive treatment with
      artemether for late-stage experimental cerebral malaria.
AB  - Cerebral malaria (CM) is associated with low nitric oxide (NO) bioavailability,
      cerebrovascular constriction, occlusion, and hypoperfusion. Administration of
      exogenous NO partially prevents the neurological syndrome and associated vascular
      pathology in an experimental CM (ECM) mouse model. In this study, we evaluated
      the effects of transdermal glyceryl trinitrate in preventing ECM and, in
      combination with artemether, rescuing late-stage ECM mice from mortality. The
      glyceryl trinitrate and/or artemether effect on survival and clinical recovery
      was evaluated in C57BL/6 mice infected with P. berghei ANKA. NO synthase (NOS)
      expression in mouse brain was determined by Western blots. Mean arterial pressure
      (MAP) and pial arteriolar diameter were monitored using a tail-cuff blood
      pressure system and a cranial window preparation, respectively. Preventative
      administration of glyceryl trinitrate at 0.025 mg/h decreased ECM mortality from
      67 to 11% and downregulated inducible NOS expression in the brain. When
      administered as adjunctive rescue therapy with artemether, glyceryl trinitrate
      increased survival from 47 to 79%. The adjunctive therapy caused a sustained
      reversal of pial arteriolar vasoconstriction in ECM mice, an effect not observed
      with artemether alone. Glyceryl trinitrate induced a 13% decrease in MAP in
      uninfected mice but did not further affect MAP in hypotensive ECM mice. Glyceryl
      trinitrate, when combined with artemether, was an effective adjunctive rescue
      treatment for ECM. This treatment ameliorated pial arteriolar vasospasm and did
      not significantly affect MAP. These results indicate that transdermal glyceryl
      trinitrate has potential to be considered as a candidate for adjunctive therapy
      for CM. 

PMID- 23979752
TI  - Bioengineered lysozyme reduces bacterial burden and inflammation in a murine
      model of mucoid Pseudomonas aeruginosa lung infection.
AB  - The spread of drug-resistant bacterial pathogens is a growing global concern and
      has prompted an effort to explore potential adjuvant and alternative therapies
      derived from nature's repertoire of bactericidal proteins and peptides. In
      humans, the airway surface liquid layer is a rich source of antibiotics, and
      lysozyme represents one of the most abundant and effective antimicrobial
      components of airway secretions. Human lysozyme is active against both Gram
      positive and Gram-negative bacteria, acting through several mechanisms, including
      catalytic degradation of cell wall peptidoglycan and subsequent bacterial lysis.
      In the infected lung, however, lysozyme's dense cationic character can result in
      sequestration and inhibition by polyanions associated with airway inflammation.
      As a result, the efficacy of the native enzyme may be compromised in the infected
      and inflamed lung. To address this limitation, we previously constructed a charge
      engineered variant of human lysozyme that was less prone to electrostatic
      mediated inhibition in vitro. Here, we employ a murine model to show that this
      engineered enzyme is superior to wild-type human lysozyme as a treatment for
      mucoid Pseudomonas aeruginosa lung infections. The engineered enzyme effectively
      decreases the bacterial burden and reduces markers of inflammation and lung
      injury. Importantly, we found no evidence of acute toxicity or allergic
      hypersensitivity upon repeated administration of the engineered biotherapeutic.
      Thus, the charge-engineered lysozyme represents an interesting therapeutic
      candidate for P. aeruginosa lung infections. 

PMID- 23979753
TI  - Human herpesvirus 6 U69 kinase phosphorylates the methylenecyclopropane
      nucleosides cyclopropavir, MBX 2168, and MBX 1616 to their monophosphates.
AB  - Dihydroxymethyl and monohydroxymethyl methylenecyclopropane nucleosides are
      effective inhibitors of both variants of human herpesvirus 6 (HHV-6). We
      investigated involvement of HHV-6 U69 protein kinase in their mechanism of
      action. Phosphorylation of the dihydroxymethyl analogue cyclopropavir and
      monohydroxymethyl nucleosides with either a 6-ether moiety (MBX 2168) or a 6
      thioether moiety (MBX 1616) with purified U69 was examined. All three compounds
      were substrates of this viral kinase and had similar Michaelis-Menten kinetic
      parameters. 

PMID- 23979754
TI  - Superoxide-mediated protection of Escherichia coli from antimicrobials.
AB  - Antimicrobial lethality is promoted by reactive oxygen species (ROS), such as
      superoxide, peroxide, and hydroxyl radical. Pretreatment with subinhibitory
      concentrations of plumbagin or paraquat, metabolic generators of superoxide,
      paradoxically reduced killing for oxolinic acid, kanamycin, and ampicillin. These
      pretreatments also reduced an oxolinic acid-mediated ROS surge. Defects in SoxS
      MarA or AcrB eliminated plumbagin- and paraquat-mediated MIC increases but
      maintained protection from killing. Thus, superoxide has both protective and
      detrimental roles in response to antimicrobial stress. 

PMID- 23979755
TI  - A novel fexA variant from a canine Staphylococcus pseudintermedius isolate that
      does not confer florfenicol resistance.
AB  - Transposon Tn558 integrated in the chromosomal radC gene was detected for the
      first time in Staphylococus pseudintermedius. It carried a novel fexA variant
      (fexAv) that confers only chloramphenicol resistance. The exporter FexAv
      exhibited two amino acid substitutions, Gly33Ala and Ala37Val, both of which seem
      to be important for substrate recognition. Site-directed mutagenesis that
      reverted the mutated base pairs to those present in the original fexA gene
      restored the chloramphenicol-plus-florfenicol resistance phenotype. 

PMID- 23979756
TI  - Comparison between the EUCAST procedure and the Etest for determination of the
      susceptibility of Candida species isolates to micafungin.
AB  - We compared the ability of the EUCAST EDef 7.2 and the Etest to detect the
      susceptibility to micafungin of 160 Candida and non-Candida clinical isolates.
      Agreement was higher when Etest MICs were obtained after 24 h of incubation;
      essential agreement was 90%, and categorical agreement was >90%. False
      susceptibility was seen only for Candida krusei (10%), and false resistance was
      observed in 6% of the isolates, ranging from 2.6% (C. glabrata) to 13% (C.
      albicans). 

PMID- 23979758
TI  - Azole resistance in Cryptococcus gattii from the Pacific Northwest: Investigation
      of the role of ERG11.
AB  - Cryptococcus gattii is responsible for an expanding epidemic of serious
      infections in Western Canada and the Northwestern United States (Pacific
      Northwest). Some patients with these infections respond poorly to azole
      antifungals, and high azole MICs have been reported in Pacific Northwest C.
      gattii. In this study, multiple azoles (but not amphotericin B) had higher MICs
      for 25 Pacific Northwest C. gattii than for 34 non-Pacific Northwest C. gattii or
      20 Cryptococcus neoformans strains. We therefore examined the roles in azole
      resistance of overexpression of or mutations in the gene (ERG11) encoding the
      azole target enzyme. ERG11/ACT1 mRNA ratios were higher in C. gattii than in C.
      neoformans, but these ratios did not differ in Pacific Northwest and non-Pacific
      Northwest C. gattii strains, nor did they correlate with fluconazole MICs within
      any group. Three Pacific Northwest C. gattii strains with low azole MICs and 2
      with high azole MICs had deduced Erg11p sequences that differed at one or more
      positions from that of the fully sequenced Pacific Northwest C. gattii strain
      R265. However, the azole MICs for conditional Saccharomyces cerevisiae erg11
      mutants expressing the 5 variant ERG11s were within 2-fold of the azole MICs for
      S. cerevisiae expressing the ERG11 gene from C. gattii R265, non-Pacific
      Northwest C. gattii strain WM276, or C. neoformans strains H99 or JEC21. We
      conclude that neither ERG11 overexpression nor variations in ERG11 coding
      sequences was responsible for the high azole MICs observed for the Pacific
      Northwest C. gattii strains we studied. 

PMID- 23979757
TI  - Mitochondria influence CDR1 efflux pump activity, Hog1-mediated oxidative stress
      pathway, iron homeostasis, and ergosterol levels in Candida albicans.
AB  - Mitochondrial dysfunction in Candida albicans is known to be associated with drug
      susceptibility, cell wall integrity, phospholipid homeostasis, and virulence. In
      this study, we deleted CaFZO1, a key component required during biogenesis of
      functional mitochondria. Cells with FZO1 deleted displayed fragmented
      mitochondria, mitochondrial genome loss, and reduced mitochondrial membrane
      potential and were rendered sensitive to azoles and peroxide. In order to
      understand the cellular response to dysfunctional mitochondria, genome-wide
      expression profiling of fzo1Delta/Delta cells was performed. Our results show
      that the increased susceptibility to azoles was likely due to reduced efflux
      activity of CDR efflux pumps, caused by the missorting of Cdr1p into the vacuole.
      In addition, fzo1Delta/Delta cells showed upregulation of genes involved in iron
      assimilation, in iron-sufficient conditions, characteristic of iron-starved
      cells. One of the consequent effects was downregulation of genes of the
      ergosterol biosynthesis pathway with a commensurate decrease in cellular
      ergosterol levels. We therefore connect deregulated iron metabolism to ergosterol
      biosynthesis pathway in response to dysfunctional mitochondria. Impaired
      activation of the Hog1 pathway in the mutant was the basis for increased
      susceptibility to peroxide and increase in reactive oxygen species, indicating
      the importance of functional mitochondria in controlling Hog1-mediated oxidative
      stress response. Mitochondrial phospholipid levels were also altered as indicated
      by an increase in phosphatidylserine and phosphatidylethanolamine and decrease in
      phosphatidylcholine in fzo1Delta/Delta cells. Collectively, these findings
      reinforce the connection between functional mitochondria and azole tolerance,
      oxidant-mediated stress, and iron homeostasis in C. albicans. 

PMID- 23979759
TI  - In vitro activity of ceftaroline-avibactam against gram-negative and gram
      positive pathogens isolated from patients in Canadian hospitals from 2010 to
      2012: results from the CANWARD surveillance study.
AB  - The in vitro activities of ceftaroline-avibactam, ceftaroline, and comparative
      agents were determined for a collection of bacterial pathogens frequently
      isolated from patients seeking care at 15 Canadian hospitals from January 2010 to
      December 2012. In total, 9,758 isolates were tested by using the Clinical and
      Laboratory Standards Institute (CLSI) broth microdilution method (document M07
      A9, 2012), with MICs interpreted by using CLSI breakpoints (document M100-S23,
      2013). Ceftaroline-avibactam demonstrated potent activity (MIC90, <= 0.5 MUg/ml)
      against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus
      mirabilis, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens,
      Morganella morganii, Citrobacter freundii, and Haemophilus influenzae; >99% of
      isolates of E. coli, K. pneumoniae, K. oxytoca, P. mirabilis, M. morganii, C.
      freundii, and H. influenzae were susceptible to ceftaroline-avibactam according
      to CLSI MIC interpretative criteria for ceftaroline. Ceftaroline was less active
      than ceftaroline-avibactam against all species of Enterobacteriaceae tested, with
      rates of susceptibility ranging from 93.9% (P. mirabilis) to 54.0% (S.
      marcescens). All isolates of methicillin-susceptible Staphylococcus aureus
      (MIC90, 0.25 MUg/ml) and 99.6% of methicillin-resistant S. aureus isolates
      (MIC90, 1 MUg/ml) were susceptible to ceftaroline; the addition of avibactam to
      ceftaroline did not alter its activity against staphylococci or streptococci. All
      isolates of Streptococcus pneumoniae (MIC90, 0.03 MUg/ml), Streptococcus pyogenes
      (MIC90, <= 0.03 MUg/ml), and Streptococcus agalactiae (MIC90, 0.015 MUg/ml)
      tested were susceptible to ceftaroline. We conclude that combining avibactam with
      ceftaroline expanded its spectrum of activity to include most isolates of
      Enterobacteriaceae resistant to third-generation cephalosporins, including
      extended-spectrum beta-lactamase (ESBL)- and AmpC-producing E. coli and ESBL
      producing K. pneumoniae, while maintaining potent activity against staphylococci
      and streptococci.

PMID- 23979760
TI  - A novel C5a-derived immunobiotic peptide reduces Streptococcus agalactiae
      colonization through targeted bacterial killing.
AB  - Streptococcus agalactiae (group B Streptococcus [GBS]) is a Gram-positive
      bacterium that colonizes the cervicovaginal tract in approximately 25% of healthy
      women. Although colonization is asymptomatic, GBS can be vertically transmitted
      to newborns peripartum, causing severe disease such as pneumonia and meningitis.
      Current prophylaxis, consisting of late gestation screening and intrapartum
      antibiotics, has failed to completely prevent transmission, and GBS remains a
      leading cause of neonatal sepsis and meningitis in the United States. Lack of an
      effective vaccine and emerging antibiotic resistance necessitate exploring novel
      therapeutic strategies. We have employed a host-directed immunomodulatory therapy
      using a novel peptide, known as EP67, derived from the C-terminal region of human
      complement component C5a. Previously, we have demonstrated in vivo that EP67
      engagement of the C5a receptor (CD88) effectively limits staphylococcal infection
      by promoting cytokine release and neutrophil infiltration. Here, using our
      established mouse model of GBS vaginal colonization, we observed that EP67
      treatment results in rapid clearance of GBS from the murine vagina. However, this
      was not dependent on functional neutrophil recruitment or CD88 signaling, as EP67
      treatment reduced the vaginal bacterial load in mice lacking CD88 or the major
      neutrophil receptor CXCr2. Interestingly, we found that EP67 inhibits GBS growth
      in vitro and in vivo and that antibacterial activity was specific to
      Streptococcus species. Our work establishes that EP67-mediated clearance of GBS
      is likely due to direct bacterial killing rather than to enhanced immune
      stimulation. We conclude that EP67 may have potential as a therapeutic to control
      GBS vaginal colonization. 

PMID- 23979761
TI  - Involvement of mutation in ampD I, mrcA, and at least one additional gene in beta
      lactamase hyperproduction in Stenotrophomonas maltophilia.
AB  - It has been reported that targeted disruption of ampD I or mrcA causes beta
      lactamase hyperproduction in Stenotrophomonas maltophilia. We show here that beta
      lactamase-hyperproducing laboratory selected mutants and clinical isolates can
      have wild-type ampD I and mrcA genes, implicating mutation of at least one
      additional gene in this phenotype. The involvement of mutations at multiple loci
      in the activation of beta-lactamase production in S. maltophilia reveals that
      there are significant deviations from the enterobacterial paradigm of AmpR
      mediated control of beta-lactamase induction. We do show, however, that S.
      maltophilia ampD I can complement a mutation in Escherichia coli ampD. This
      suggests that an anhydromuropeptide degradation product of peptidoglycan is used
      to activate AmpR in S. maltophilia, as is also the case in enteric bacteria. 

PMID- 23979763
TI  - A Perspective on HRT for Women.

PMID- 23979762
TI  - Flucytosine antagonism of azole activity versus Candida glabrata: role of
      transcription factor Pdr1 and multidrug transporter Cdr1.
AB  - Infections with the opportunistic yeast Candida glabrata have increased
      dramatically in recent years. Antifungal therapy of yeast infections commonly
      employs azoles, such as fluconazole (FLC), but C. glabrata frequently develops
      resistance to these inhibitors of ergosterol biosynthesis. The pyrimidine analog
      flucytosine (5-fluorocytosine [5FC]) is highly active versus C. glabrata but is
      now rarely used clinically due to similar concerns over resistance and, a related
      concern, the toxicity associated with high doses used to counter resistance.
      Azole-5FC combination therapy would potentially address these concerns; however,
      previous studies suggest that 5FC may antagonize azole activity versus C.
      glabrata. Here, we report that 5FC at subinhibitory concentrations antagonized
      the activity of FLC 4- to 16-fold versus 8 of 8 C. glabrata isolates tested. 5FC
      antagonized the activity of other azoles similarly but had only indifferent
      effects in combination with unrelated antifungals. Since azole resistance in C.
      glabrata results from transcription factor Pdr1-dependent upregulation of the
      multidrug transporter gene CDR1, we reasoned that 5FC antagonism might be
      similarly mediated. Indeed, 5FC-FLC antagonism was abrogated in pdr1Delta and
      cdr1Delta strains. In further support of this hypothesis, 5FC exposure induced
      CDR1 expression 6-fold, and this upregulation was Pdr1 dependent. In contrast to
      azoles, 5FC is not a Cdr1 substrate and so its activation of Pdr1 was unexpected.
      We observed, however, that 5FC exposure readily induced petite mutants, which
      exhibit Pdr1-dependent CDR1 upregulation. Thus, mitochondrial dysfunction
      resulting in Pdr1 activation is the likely basis for 5FC antagonism of azole
      activity versus C. glabrata. 

PMID- 23979764
TI  - The role of the pharmacist in diabetes care.

PMID- 23979765
TI  - Understanding feline hyperthyroidism.

PMID- 23979766
TI  - Sterile vancomycin pluronic gel for implantation in the chest-wall cavity to
      treat resistant pheumococcus.

PMID- 23979767
TI  - Application of USP-NF Standard to Pharmacy Compounding.

PMID- 23979768
TI  - Basics of compounding for pediculosis.

PMID- 23979769
TI  - Quality-control analytical methods: refractometry.

PMID- 23979770
TI  - Stability of oral liquid dosage forms of glycopyrrolate prepared with the use of
      powder.
AB  - A previously developed stability-indicating high-performance liquid
      chromatographic assay method was used to investigate the stability of
      glycopyrrolate in oral liquid dosage forms (0.5 mg/mL) that contained a 0.05-M
      phosphate buffer of pH 5.6 and either 10% sorbitol or 10% sucrose as the
      sweetening agent. The decomposition product and sorbitol or sucrose did not
      interfere with the assay procedure. The liquid dosage forms were prepared using
      commercially available powder. After 129 days of storage at 25 deg C, the loss in
      potency was less than 6%. The physical appearance of this dosage form did not
      change during the study period. The pH value of the dosage forms in sorbitol did
      not change from the original value of 5.6. The pH value of the dosage forms in
      sucrose decreased from 5.6 to 4.8 after 129 days of storage at 25 deg C. 

PMID- 23979771
TI  - Formulation and accelerated stability studies for an extemporaneous suspension of
      amiodarone hydrochloride.
AB  - Amiodarone is commercially available as both a tablet and an injectable
      formulation. It is widely dispensed as an extemporaneously compounded suspension
      for pediatric and geriatric patients. Extensive stability data at numerous
      temperatures and a calculated shelf life based on kinetics for such a formulation
      have not been reported. Refrigeration and room temperature data for finite times
      have been reported in the literature. In this study, a stable extemporaneous
      formulation of amiodarone hydrochloride was formulated using Paceron tablets. The
      formulation consisted of 0.75% carboxymethylcellulose and 0.75% Veegum as
      suspending agents; 25% sucrose, provided as simple syrup; and aqueous strawberry
      concentrate as flavor. A total of 2.5L of the formulation was compounded and
      stored in quanitites of 150 mL in 8-oz glass containers. The initial drug content
      was determined by reverse-phase high-performance liquid chromatography, with a
      method that was developed in our laboratory. The stability study was carried out
      by storing three containers at five different temperatures, namely 4, 30, 40, 50,
      and 60 deg C. The suspension was analyzed at the end of 2, 6, 12, 24, and 48
      hours at 7 days, and, therafter, at the end of every week for 13 weeks. The
      percentage of drug remaining was plotted against time for each temperature. The
      slope of the regression line was obtained for each temperature and the zero-order
      degradation rate constant obtained. The logarithm of the zero-order degradation
      rate constants was plotted against the inverse of the temperature in degrees
      Kelvin to obtain the Arrhenius plot. From the regression line for the Arrhenius
      plot, the zero-order degradation constant at 25 deg C was calculated to be 0.0517
      day -1. The shelf life for the formulation at 25 deg C was calculated to be 193.4
      days; the shelf life under refrigeration (4 deg C) was found to be 677.3 days.
      The degradation products were characterized using high-performance liquid
      chromatographic-mass spectrometry. Data obtained from the analysis suggested that
      amiodarone cleaved at its ketone and ether linkages to yield corresponding
      degradation products. 

PMID- 23979772
TI  - Educating the caregiver and community pharmacist to facilitate provision of
      consistent compounded medications from the inpatient to ambulatory settings.
AB  - The purpose of this pharmaceutical-care project was to demonstrate that educating
      a patient's caregiver about extemporaneously compounded medications prior to the
      patient's discharge and verbally assisting the community pharmacist in the
      preparation of the compounds can reduce delays and avoid problems in filling
      these compounds. Two sets of patients and their caregivers were selected based on
      the patients' receiving compounded medication as inpatients. The first set of
      caregivers (prestudy) were contacted and surveyed about obtaining the patient's
      compounded medications after hospital discharge. The second set of caregivers
      (poststudy) were counseled and given written information about compounded
      medications by the compounding pharmacist prior to hospital discharge. Within a
      month after discharge, the caregivers were contacted and surveyed about their
      experience obtaining the compounded medication. The pre- and poststudy surveys
      revealed that 58% of the caregivers in the prestudy group reported delays or
      problems in getting the compounded medication filled, while only 15% of the
      caregivers in the poststudy group reported delays or problems. Only 25% of the
      caregivers in the prestudy had their compounded prescription prepared by an
      independent pharmacy or hospital-based pharmacy specializing in compounding. In
      the poststudy group, 61% of the caregivers had their compounded prescription
      prepared by an independent pharmacy or hospital-based pharmacy specializing in
      compounding. Educating the caregiver about the patient's compounded medication
      can siginificantly reduce problems and delays in filling these compounds after
      the patient is discharged. If the community pharmacy is provided with contact
      information from the hospital compounding pharmacy, the community pharmacist can
      acquire information about the patient's medication to assist in the compounding
      of a comparable product, thereby reducing problems and delays in filling these
      compounds. 

PMID- 23979773
TI  - PostScription: Compounding Paradox: Taught Less and Practiced More.

PMID- 23979774
TI  - Good people do bad things.

PMID- 23979775
TI  - DOCK4 deletion at 7q31.1 in a de novo acute myeloid leukemia with a normal
      karyotype.
AB  - BACKGROUND: Acute myeloid leukemia with a normal karyotype (NK-AML) has been
      assigned to an intermediate prognostic risk group. However, there is a marked
      variability in outcome within this group of AML, suggesting a significant
      biological and molecular heterogeneity. Chromosomal abnormalities may be cryptic
      by metaphase cytogenetics, but still have an impact on the process of
      leukemogenesis and/or the clinical outcome of NK-AML. Therefore, we analyzed the
      genomic complement of NK-AML cases to search for the presence of submicroscopic
      genomic imbalances. METHODS: We applied high-resolution oligo-based aCGH analysis
      to a cohort of AML patients with a normal karyotype, and FISH to validate the
      aCGH findings. Relative gene expression levels were examined by qPCR. RESULTS:
      High-resolution aCGH analysis of 21 NK-AML patients revealed one patient with a
      rare submicroscopic deletion at 7q31.1. This female patient exhibited a rapid
      disease progression and a dismal outcome. The deletion was mono-allelic,
      approximately 189,1 kb in size, and encompassed the major 3' part of the DOCK4
      gene. The expression level of the DOCK4 gene in her leukemic cells was decreased
      when compared to CD34+ cells from healthy controls. When compared to AML patients
      with -7/del(7q) as the sole chromosomal anomaly, the DOCK4 expression level was
      found to be similarly low. CONCLUSIONS: This is the first report of an acquired
      partial deletion of the DOCK4 gene in a patient with de novo NK-AML. DOCK4 is a
      strong tumor suppressor candidate, required for GTPase activation in signal
      transduction pathways controlling cellular proliferation, adhesion, migration and
      phagocytosis. Our findings may be relevant for understanding of the process of
      leukemogenesis and the response to therapy in a subset of NK-AML patients.

PMID- 23979776
TI  - Associations of prepartum body condition score with occurrence of clinical
      endometritis and resumption of postpartum ovarian activity in dairy cattle.
AB  - This study was performed to investigate the effect of periparturient body
      condition score on the occurrence of clinical endometritis and postpartum
      resumption of ovarian activity in dairy cows. Eighty-seven lactating Holstein
      cows, fed with a total mixed ration diet, were included into the study. Body
      condition scoring (using a 5-point scale with quarter-point divisions) was
      performed by the same investigator using the visual technique every 2 weeks, from
      2 weeks before until 6 weeks after calving. Palpation of the reproductive tract
      and ultrasonographic assessment of ovaries for detection of corpus luteum using a
      rectal linear probe was also performed at 2, 4, and 6 weeks after calving. Cows
      with clinical endometritis had significantly lower body condition score (BCS)
      than normal cows at all weeks pre- and postcalving, and cows that did not ovulate
      until 45 days after calving had a significantly lower BCS pre- and postpartum.
      Cows that did not ovulate until 45 days after calving also lost more BCS from 2
      weeks before to 4 weeks after calving. Besides, first ovulation after calving
      take occurred later in cows with clinical endometritis compared to normal cows (P
      < 0.05). In conclusion, low BCS is a risk factor for postpartum endometritis and
      delayed cyclicity in dairy cows. BCS loss from dry-off to early lactation and
      occurrence of clinical endometritis can significantly affect postpartum ovarian
      activity. 

PMID- 23979777
TI  - Relationship between anthropometric measures and cardiovascular risk factors in
      children and adolescents.
AB  - BACKGROUND: Obesity has been identified as an important risk factor in the
      development of cardiovascular diseases; however, other factors, combined or not
      with obesity, can influence cardiovascular risk and should be considered in
      cardiovascular risk stratification in pediatrics. OBJECTIVE: To analyze the
      association between anthropometry measures and cardiovascular risk factors, to
      investigate the determinants to changes in blood pressure (BP), and to propose a
      prediction equation to waist circumference (WC) in children and adolescents.
      METHODS: We evaluated 1,950 children and adolescents, aged 7 to 18 years.
      Visceral fat was assessed by WC and waist-hip relationship, BP and body mass
      index (BMI). In a randomly selected subsample of these volunteers (n = 578),
      total cholesterol, glucose and triglycerides levels were evaluated. RESULTS: WC
      was positively correlated with BMI (r = 0.85; p < 0.001) and BP (SBP r = 0.45 and
      DBP = 0.37; p < 0.001). Glycaemia and triglycerides showed a weak correlation
      with WC (r = 0.110; p = 0.008 e r = 0.201; p < 0.001, respectively). Total
      cholesterol did not correlate with any of the variables. Age, BMI and WC were
      significant predictors on the regression models for BP (p < 0.001). We propose a
      WC prediction equation for children and adolescents: boys: y = 17.243 + 0.316
      (height in cm); girls: y = 25.197 + 0.256 (height in cm). CONCLUSION: WC is
      associated with cardiovascular risk factors and presents itself as a risk factor
      predictor of hypertension in children and adolescents. The WC prediction equation
      proposed by us should be tested in future studies.

PMID- 23979778
TI  - Big endothelin-1 and nitric oxide in hypertensive elderly patients with and
      without obstructive sleep apnea-hypopnea syndrome.
AB  - BACKGROUND: The role of oxidative stress in hypertensive elderly patients with
      obstructive sleep apnea-hypopnea syndrome (OSAHS) is unknown. OBJECTIVE: The
      purpose was to evaluate the levels of big endothelin-1 (Big ET-1) and nitric
      oxide (NO) in elderly hypertensive patients with and without moderate to severe
      OSAHS. METHODS: Volunteers were hospitalized for 24 h. We obtained the following
      data: body mass index (BMI); 24-ambulatory blood pressure monitoring; and current
      medication. Arterial blood was collected at 7 pm and 7 am for determining plasma
      NO and Big ET-1 levels. Pulse oximetry was performed during sleep. Pearson's or
      Spearman's correlation and univariate analysis of variance were used for
      statistical analysis. RESULTS: We studied 25 subjects with OSAHS (group 1) and 12
      without OSAHS (group 2) aged 67.0 +/- 6.5 years and 67.8 +/- 6.8 years,
      respectively. No significant differences were observed between the groups in BMI;
      number of hours of sleep; 24-h systolic and diastolic BPs; awake BP, sleep BP and
      medications to control BP between groups. No differences were detected in plasma
      Big ET-1 and NO levels at 19:00 h, but plasma Big ET-1 levels at 7:00 h were
      higher in group 1 (p =0.03). In group 1, a negative correlation was also observed
      between the mean arterial oxyhemoglobin saturation level, 24-h systolic BP (p =
      0.03, r = -0.44), and Big ET-1 (p = 0.04, r = -0.41). CONCLUSIONS: On comparing
      elderly hypertensive patients with and without OSAHS having similar BP and BMI,
      we observed higher Big ET-1 levels After sleep in the OSAHS group. NO levels did
      not differ between the hypertensive patients with or without OSAHS.

PMID- 23979779
TI  - Pulmonary arterial hypertension: use of delayed contrast-enhanced cardiovascular
      magnetic resonance in risk assessment.
AB  - BACKGROUND: Pulmonary arterial hypertension is a severe and progressive disease.
      Its early diagnosis is the greatest clinical challenge. OBJECTIVE: To evaluate
      the presence and extension of the delayed myocardial contrast-enhanced
      cardiovascular magnetic resonance, as well as to verify if the percentage of the
      myocardial fibrosis mass is a severity predictor. METHODS: Cross-sectional study
      with 30 patients with pulmonary arterial hypertension of groups I and IV,
      subjected to clinical, functional and hemodynamic evaluation, and to cardiac
      magnetic resonance. RESULTS: The mean age of patients was 52 years old, with
      female predominance (77%). Among the patients, 53% had right ventricular failure
      at diagnosis, and 90% were in functional class II/III. The mean of the 6-minute
      walk test was 395 m. In hemodynamic study with right catheterism, the mean
      average pulmonary arterial pressure was 53.3 mmHg, of the cardiac index of 2.1
      L/min.m(2), and median right atrial pressure was 13.5 mmHg. Delayed myocardial
      contrast-enhanced cardiovascular magnetic resonance was found in 28 patients. The
      mean fibrosis mass was 9.9 g and the median percentage of fibrosis mass was
      6.17%. The presence of functional class IV, right ventricular failure at
      diagnosis, 6-minute walk test < 300 meters and right atrial pressure > 15 mmHg,
      with cardiac index < 2.0 L/min.m(2), there was a relevant association with the
      increased percentage of myocardial fibrosis. CONCLUSION: The percentage of the
      myocardial fibrosis mass indicates a non-invasive marker with promising
      perspectives in identifying patients with high risk factors for pulmonary
      hypertension.

PMID- 23979780
TI  - Features of the onset of Takayasu's arteritis according to gender.
AB  - BACKGROUND: Although there are various published epidemiological studies
      regarding Takayasu's arteritis (TA), none have analyzed the influence of gender
      on the clinical and laboratory manifestations or vascular alterations at disease
      onset. OBJECTIVES: To analyze the influence of gender on clinical and laboratory
      manifestations and variations in vascular imaging at TA onset. METHODS: A
      retrospective, unicentric cohort study that evaluated 55 consecutive TA patients
      between 1982 and 2012. All available clinical data and laboratory test results
      related to the onset of the disease were analyzed. We included only patients aged
      12-35 years at diagnosis to exclude age-related factors. RESULTS: We analyzed 17
      men and 38 women, mostly Caucasian, with a comparable mean age between genders.
      There was no gender difference regarding the clinical or laboratory
      characteristics, comorbidities, or smoking habit, except for abdominal pain,
      which was more common in men. Regarding vascular lesions, the presence of
      ascending aortic aneurysms was significantly more frequent in males. Male gender
      represented an independent risk factor for the occurrence of abdominal pain and
      ascending aortic aneurysms in TA patients. CONCLUSION: Abdominal pain and
      ascending aortic aneurysms occurred more frequently in men with TA, suggesting a
      more severe disease profile in males.

PMID- 23979781
TI  - Dental findings and identification of undiagnosed hyperglycemia.
AB  - A change in the American Diabetes Association guidelines added hemoglobin A1c
      (HbA1c) to the assays for diabetes diagnosis, but evidence suggests that glucose
      vs. HbA1c criteria may identify different segments of the affected population. We
      previously demonstrated that oral findings offer an opportunity for the detection
      of undiagnosed abnormal fasting plasma glucose (FPG) among dental patients who
      present with diabetes risk factors. In this new cross-sectional study, we sought
      to extend these observations. The first goal, using data from 591 new
      participants, was to assess our previously identified hyperglycemia detection
      models when HbA1c is used for case definition. The second goal, using data from
      our total cohort of 1,097 participants, was to evaluate the models' performance
      regardless of whether an FPG or an HbA1c is used for diagnosis. The presence of
      >= 26% teeth with deep pockets or >= 4 missing teeth correctly identified 72% of
      pre-diabetes or diabetes cases in the HbA1c sample and 75% in the total
      population. The addition of a point-of-care HbA1c >= 5.7% increased correct
      identification to 87% and 90%, respectively. These results demonstrate the
      validity of our prediction models regardless of the test used for diabetes or pre
      diabetes diagnosis in the clinical setting and underscore the contribution
      dentists can make. 

PMID- 23979782
TI  - Body mass index, depression, and condom use among HIV-infected men who have sex
      with men: a longitudinal moderation analysis.
AB  - Findings have been inconsistent regarding the association of obesity and sexual
      risk behaviors. The purpose of the current study was to assess the prospective
      nature of body mass index (BMI), depression, and their interaction in predicting
      condom use during anal intercourse among HIV-infected men who have sex with men
      (MSM). The sample (N = 490) was obtained from a large, HIV clinical cohort from
      four sites across the U.S. The following inclusion criteria were employed:
      identification as MSM and had completed at least one wave of patient-reported
      measures (e.g., depression, as measured by the PHQ-9) in the clinical cohort
      study. Longitudinal linear mixed-effects modeling revealed a significant BMI by
      depression interaction. Depressive symptoms were predictive of less frequent
      condom use for obese but not overweight men. Analogous results were found in
      regard to comparisons between normal weight and overweight men. Obesity, in the
      context of depression, is a risk factor for unprotected anal intercourse among
      HIV-infected MSM. Cognitive behavioral interventions to reduce HIV transmission
      risk behaviors among HIV-infected MSM should adopt an integrated perspective,
      combining sexual risk reduction with treatment for depression and body-related
      concerns.

PMID- 23979783
TI  - Body mass index, body esteem, and unprotected receptive anal intercourse among
      young men who have sex with men who seek partners online.
AB  - Research examining the relationship between body mass index (BMI) and sexual risk
      outcomes among men who have sex with men (MSM) has yielded inconsistent results.
      Using a web-based survey, single-identified (e.g., not in a relationship) young
      MSM (N = 431) between the ages of 18 and 24 years who sought romantic partners
      online were asked to respond to items regarding their BMI, body image (e.g.,
      attribution, dissatisfaction, and pride), and sexual risk behaviors. We used
      Poisson regressions to examine the relationships between BMI, body image, and the
      number of unprotected receptive anal intercourse (URAI) occasions and partners in
      the past 2 months. We found a curvilinear relationship between BMI and URAI
      occasions, and a linear relationship between BMI and URAI partners. These
      relationships persisted after accounting for body image. Further, we found that
      body attribution served as a protective factor whereas body pride served as a
      risk factor. We discuss the implications of our findings for sexual health
      education and HIV prevention.

PMID- 23979784
TI  - Friendship after a friends with benefits relationship: deception, psychological
      functioning, and social connectedness.
AB  - Friends with benefits (FWB) relationships are formed by an integration of
      friendship and sexual intimacy, typically without the explicit commitments
      characteristic of an exclusive romantic relationship. The majority of these
      relationships do not transition into committed romantic relationships, raising
      questions about what happens to the relationship after the FWB ends. In a sample
      of 119 men and 189 women university students, with a median age of 19 years and
      the majority identified as Caucasian (63.6 %), we assessed relationship
      adjustment, feelings of deception, perception of the FWB relationship and
      friendship, social connectedness, psychological distress, and loneliness. Results
      demonstrated that the majority of FWB relationships continued as friendships
      after the sexual intimacy ceased and that about 50 % of the participants reported
      feeling as close or closer to their FWB partner. Those who did not remain friends
      were more likely to report that their FWB relationship was more sex- than
      friendship-based; they also reported higher levels of feeling deceived by their
      FWB partner and higher levels of loneliness and psychological distress, but lower
      levels of mutual social connectedness. Higher levels of feeling deceived were
      related to feeling less close to the post-FWB friend; also, more sex-based FWB
      relationships were likely to result in post-FWB friendships that were either more
      or less close (as opposed to unchanged). FWB relationships, especially those that
      include more attention to friendship based intimacy, do not appear to negatively
      impact the quality of the friendship after the "with benefits" ends.

PMID- 23979785
TI  - Attitudes of Lebanese university students towards surgical hymen reconstruction.
AB  - Many cultural and religious beliefs place virginity at a high level of social
      significance, in that women who lose their virginity before marriage may face
      humiliation, ostracism, divorce, and extreme violence. This led to an increase in
      the demand for virginity restoration through surgical hymen reconstruction among
      these cultures. However, data regarding the acceptance of hymenoplasty in
      societies that consider sexuality a taboo are scarce. In this cross-sectional
      study, we investigated the effects of gender and religion on sexual attitudes
      towards hymenoplasty, premarital sex, and virginity in a sample of 600 Lebanese
      university students. Our findings showed that approval of hymenoplasty was low
      among participants regardless of gender (25.7 % men vs. 19.1 % women) and
      religious affiliations (22.5 % Muslims vs. 22.3 % Christians). Arguments for
      rejection were rooted in moral ethics and personal convictions: "form of
      deceiving and cheating" (80.7 %) and "betrayal of honesty in the relationship"
      (80.4 %). Reasons for acceptance included: personal belief in "women's rights,
      autonomy, and freedom" (72.2 %) and "physical harm and death" (63.5 %).Male
      participants were more likely to approve premarital coital sex than females (61.0
      vs. 27.3 %). Muslims were also more likely to reject marrying a non-virgin than
      Christians (39.9 vs. 18.0 %). Female participants expressed more tolerance
      towards marrying a non-virgin male partner (78.3 vs. 57.3 %). Low acceptance of
      hymenoplasty among Lebanese university students was found to be related to moral
      ethics and personal convictions independently from gender and religious
      affiliation. Differences in sexual attitudes towards premarital coital sex and
      virginity, however, were more significantly influenced by culture and religion.

PMID- 23979786
TI  - No attitude, no standing around: the organization of social and sexual
      interaction at a gay male private sex party in New York city.
AB  - Following the onset of the AIDS epidemic, many jurisdictions have outlawed
      commercial sex-on-premise venues (bathhouses, adult theaters, sex clubs), greatly
      changing the culture of public or group sex. Today, in New York City (NYC),
      private sex parties are the main venues for group sex. Dozens of such events are
      held on a regular basis in the city, attracting sometimes a few hundred
      participants. Past research in group sex venues shows that different spaces allow
      for different kinds of sexual and social interaction. What are the norms of
      interaction of today's private sex parties? This article answers this question by
      using data collected ethnographically in one recurring gay male private sex party
      in NYC. The event was a small organization that brought all its participants
      together in one space at the same time, thus creating great physical intimacy and
      leading to convivial socialization and interpersonal bonding. This differs from
      the model of anonymous and impersonal sex that previous researchers have seen in
      public and commercial spaces. Private sex parties present risk for the
      transmission of HIV and other sexually-transmitted infections, but their
      organization and norms of interaction also present new avenues for prevention.
      Policy-makers should work to make these places safer rather than outlawing them. 

PMID- 23979787
TI  - The effects of weight loss on FABP4 and RBP4 in obese women with metabolic
      syndrome.
AB  - Fat accumulation is associated with the release of many novel adipokines such as
      retinol-binding protein 4 and fatty acid-binding protein 4. These adipokines have
      been linked to insulin resistance, metabolic syndrome, type 2 diabetes and
      cardiovascular disease. Since weight loss is the first step for the treatment of
      metabolic syndrome, which increases the risks for both type 2 diabetes and
      cardiovascular disease, we have investigated the effects of weight loss on serum
      retinol-binding protein 4 and fatty acid-binding protein 4 in obese individuals
      with this syndrome. Twenty-nine obese female subjects with metabolic syndrome,
      aged 18-62 years completed a 2-month weight loss diet plan. Data were collected
      from dual-energy X-ray absorptiometry and indirect calorimetry. Blood was taken
      at baseline and at 2 months and assayed for adipokines, lipids, and insulin
      resistance parameters. The change in circulating fatty acid-binding protein 4
      levels were inversely correlated with total weight loss (p<0.02) and lean mass
      loss (p<0.01), but not with fat mass loss. Retinol-binding protein 4 levels did
      not track with any measure of body composition. Changes in leptin levels were
      found to correlate with weight loss (p<0.02), fat loss (p<0.03), and lean mass
      loss (p<0.05). Fatty acid-binding protein 4 levels increased and retinol-binding
      protein 4 levels did not change during moderate weight loss in obese women with
      metabolic syndrome; however, several other risk factors for type 2 diabetes and
      cardiovascular disease did improve with weight loss. 

PMID- 23979788
TI  - Serum preadipocyte factor-1 concentrations in females with obesity and type 2
      diabetes mellitus: the influence of very low calorie diet, acute
      hyperinsulinemia, and fenofibrate treatment.
AB  - Appropriate differentiation capacity of adipose tissue significantly affects its
      ability to store lipids and to protect nonadipose tissues against lipid spillover
      and development of insulin resistance. Preadipocyte factor-1 (Pref-1) is an
      important negative regulator of preadipocyte differentiation. The aim of our
      study was to explore the changes in circulating Pref-1 concentrations in female
      subjects with obesity (OB) (n=19), females with obesity and type 2 diabetes
      mellitus (T2DM) (n=22), and sex- and age-matched healthy control subjects (C)
      (n=22), and to study its modulation by very low calorie diet (VLCD), acute
      hyperinsulinemia during isoglycemic-hyperinsulinemic clamp, and 3 months'
      treatment with PPAR-alpha agonist fenofibrate. At baseline, serum Pref-1
      concentrations were significantly higher in patients with T2DM compared to
      control group, while only nonsignificant trend towards higher levels was observed
      in OB group. 3 weeks of VLCD decreased Pref-1 levels in both OB and T2DM group,
      whereas 3 months of fenofibrate treatment had no significant effect.
      Hyperinsulinemia during the clamp significantly suppressed Pref-1 levels in both
      C and T2DM subjects and this suppression was unaffected by fenofibrate treatment.
      In a combined population of all groups, circulating Pref-1 levels correlated
      positively with insulin, leptin and glucose levels and HOMA (homeostasis model
      assessment) index. We conclude that elevated Pref-1 concentrations in T2DM
      subjects may contribute to impaired adipose tissue differentiation capacity
      associated with insulin resistance in obese patients with T2DM. The decrease of
      Pref-1 levels after VLCD may be involved in the improvement of metabolic status
      and the amelioration of insulin resistance in T2DM patients. 

PMID- 23979789
TI  - Effects of dietary energy density on serum adipocytokine levels in diabetic
      women.
AB  - This study was aimed to assess the effect of dietary energy density (kcal/g) on
      serum levels of adipocytokines of type 2 diabetic women. In this randomized
      parallel design clinical trial, a total of 60 diabetic women (aged 30-60 years;
      BMI>25 kg/m2) were assigned to consume either a low-energy dense (LED) (65% of
      energy from carbohydrates and 25% from fats), normal-energy dense (NED) (60% from
      carbohydrates, 30% from fats), or high-energy dense (HED) diet (55% from
      carbohydrates and 35% from fats) for 8 weeks. The low-energy dense diet was rich
      in fruits, vegetables, whole grains, and water, while the high-energy dense diet
      was rich in fats and oils and limited in fruits and vegetables as compared with
      the normal-dense diet. At baseline and at the end of intervention fasting blood
      samples were taken to assess metabolic profile. Women in the LED group consumed
      significantly more dietary fiber (p<0.001), fruits (p<0.001) and vegetables
      (p<0.001) than those in the NED and HED groups. We failed to find a significant
      effect of dietary energy density (kcal/g) on serum adiponectin and visfatin
      levels. Even the within-group changes in serum adiponectin and visfatin levels
      were not significant. Consumption of LED and NED diets resulted in a significant
      increase in serum chemerin levels (p=0.04). Comparison of mean changes of serum
      chemerin levels across 3 groups revealed a significant difference (p=0.04). Our
      study provides evidence indicating that consumption of HED diet for 8 weeks among
      diabetic patients prevented the increase in serum chemerin levels compared with
      LED and NED diets. Furthermore, we found no significant effect of dietary energy
      density (kcal/g) on serum adiponectin and visfatin concentrations in the current
      study.

PMID- 23979790
TI  - The expression of 11beta-HSDs, GR, and H6PDH in subcutaneous adipose tissue from
      polycystic ovary syndrome subjects.
AB  - The aim of the work was to investigate the expression of 11beta-hydroxysteroid
      dehydrogenase (11beta-HSD) type 1 and 2, hexose-6-phosphate dehydrogenase
      (H6PDH), and glucocorticoids receptor (GR) mRNA in subcutaneous adipose tissue
      (SAT) from obese women with or without polycystic ovary syndrome (PCOS), and the
      association between their expression and the adipocytokines' concentration.
      Sixteen women with PCOS (group P) and 18 age- and BMI-matched control women
      (group C) were enrolled for the study. Subcutaneous adipose tissue was collected
      from the abdomen. The genes' expression was detected by real-time PCR, and the
      adipocytokines' concentration was measured by ELISA. Peripheral insulin
      sensitivity was assessed by homeostatic assessment model of insulin resistance
      (HOMA-IR). beta-cell function was assessed by homeostasis model assessment of
      beta-cell function (HOMA-IS). The expression of 11beta-HSD1 mRNA was
      significantly higher in PCOS subjects (p<0.05) than controls; there was no
      difference for the expression of 11beta-HSD2, GR, and H6PDH mRNA between the 2
      groups. The stepwise multiple linear regression analysis showed that the mRNA
      level of 11beta-HSD1 was positively correlated to the concentration of the serum
      tumor necrosis factor-alpha (TNF-alpha). Expression of 11beta-HSD1 mRNA was
      increased in the SAT from the women with PCOS, which may contribute to the
      increased local active glucocorticoids (cortisol), and subsequently affects the
      secretion of the local adipose tissue. 

PMID- 23979791
TI  - Effect of membrane solubilization on the inhibition of rat and hamster liver
      microsomal type I 11beta-hydroxysteroid dehydrogenase by bile acids.
AB  - The aim of this study was to investigate the differences between rats and
      hamsters, Two of the most widely used experimental animals, with respect to the
      effects of microsomal membrane solubilization on the inhibition of liver 11beta
      hydroxysteroid dehydrogenase (11beta-HSDI) enzyme by bile acids. Liver microsome
      fractions were prepared, and the 11beta-HSDI enzymatic activity was measured
      using cortisone as a substrate. The substrate and various concentrations of bile
      acids were added to the assay mixtures. After incubation, the products were
      extracted and analyzed using high-performance liquid chromatography. To
      investigate the effect of detergent on the inhibitory effects of bile acids, we
      conducted inhibition tests using Triton X-100-solubilized animal liver
      microsomes. When solubilized microsomes were used, all bile acids inhibited
      11beta-HSDI from rats and hamsters to various degrees. 7alpha-Hydroxycholanoic
      acids (cholic acid and chenodeoxycholic acid) in particular had strong inhibitory
      activities. In hamsters, 7beta-hydroxycholanoic acid (ursodeoxycholic acid) was
      the strongest inhibitor among the bile acids tested, although its effect was not
      very strong. When nonsolubilized microsomes were used, deoxycholic acid did not
      inhibit but rather enhanced the enzymatic activity in both animals. Microsomal
      content of cholesterol and phospholipids are significantly different between rats
      and hamsters. Species differences in bile acid inhibition of nonsolubilized
      microsomes might be reflected not only by structural difference of bile acids,
      which affect membrane solubilization and enzyme activity directly, but also
      species difference in microsomal membrane lipid content. 

PMID- 23979792
TI  - Hypothalamic QRFP: regulation of food intake and fat selection.
AB  - QRFP, a member of the RFamide-related peptide family, is a strongly conserved
      hypothalamic neuropeptide that has been characterized in various species. Prepro
      QRFP mRNA expression is localized to select regions of the hypothalamus, which
      are involved in the regulation of feeding behavior. The localization of the
      peptide precursor has led to the assessment of QRFP on feeding behaviors and the
      orexigenic effects of QRFP have been detected in mice, rats, and birds. QRFP acts
      in a macronutrient specific manner in satiated rats to increase the intake of a
      high fat diet, but not the intake of a low fat diet, and increases the intake of
      chow in food-restricted rats. Studies suggest that QRFP's effects on food intake
      are mediated by the adiposity signal, leptin, and hypothalamic neuropeptides.
      Additionally, QRFP regulates the expression and release of hypothalamic
      Neuropeptide Y and proopiomelanocortin/alpha-Melanocyte-Stimulating Hormone. QRFP
      binds to receptors throughout the brain, including regions associated with food
      intake and reward. Taken together, these data suggest that QRFP is a mediator of
      motivated behaviors, particularly the drive to ingest high fat food. The present
      review discusses the role of QRFP in the regulation of feeding behavior, with
      emphasis on the intake of dietary fat. 

PMID- 23979794
TI  - Forensic proteomics of poxvirus production.
AB  - The field of microbial forensics has recently sought to develop methods to
      discern biological signatures to indicate production methods for biological
      agents. Viral agents have received less attention to date. Their obligate
      propagation in living cells makes purification from cellular material a
      challenge. This leads to potential carryover of protein-rich signatures of their
      production system. Here we have explored a proteomic analysis of vaccinia virus
      as a model poxvirus system in which to compare samples of virus propagated in
      different cell lines and subjected to different purification schemes. The
      proteomic data sets indicated viral, host cell and culture medium proteins.
      Several layers of data analysis were applied to build confidence in the peptide
      identification and capture information on the taxonomic utility of each. The
      analysis showed clear shifts in protein profiles with virus purification, with
      successive gradient purification steps showing different levels of viral protein
      enrichment. Peptides from cellular proteins, including those present in purified
      virus preparations, provided signatures which enabled discrimination of cell line
      substrates, including distinguishing between cells derived from different primate
      species. The ability to discern multiple aspects of viral production demonstrates
      the potential value of proteomic analysis as tool for microbial forensics. 

PMID- 23979793
TI  - Abiraterone acetate: targeting persistent androgen dependence in castration
      resistant prostate cancer.
AB  - Abiraterone acetate is the first second-line hormonal agent proven to improve
      survival in metastatic castration-resistant prostate cancer. It selectively
      inhibits cytochrome P450 17 (CYP17) alpha-hydroxylase and cytochrome17,20
      (C17,20)-lyase, which are enzymes critical for androgen synthesis. Abiraterone
      acetate was initially approved in the United States in 2011 after demonstrating a
      4-month survival benefit in docetaxel-refractory metastatic prostate cancer. The
      FDA recently expanded its indication for use in the pre-chemotherapy setting
      after it elicited significant delays in disease progression and a strong trend
      for increased overall survival in phase III studies. Ongoing investigations of
      abiraterone are evaluating its efficacy in earlier disease states, exploring its
      synergy in combination with other therapeutic agents, and assessing the necessity
      for administration of concurrent steroids and gonadal suppression. The
      identification and development of predictive biomarkers will optimize the
      incorporation of abiraterone into the management of advanced prostate cancer. 

PMID- 23979795
TI  - Standards of scoring, monitoring, and parameter targeting in German neurocritical
      care units: a national survey.
AB  - BACKGROUND: Optimal management of physiological parameters in
      neurological/neurosurgical intensive care units (NICUs) is largely unclear as
      high-quality evidence is lacking. The aim of this survey was to investigate if
      standards exist in the use of clinical scores, systemic and cerebral monitoring
      and the targeting of physiology values and in what way this affects clinical
      management in German NICUs. METHODS: National survey, on-line anonymized
      questionnaire. German departments stating to run a neurological, neurosurgical or
      interdisciplinary neurological/neurosurgical intensive care unit were identified
      by a web-based search of all German hospitals and contacted via email. RESULTS:
      Responses from 78 German NICUs were obtained. Of 19 proposed
      clinical/laboratory/radiological scores only 5 were used regularly by >60 %.
      Bedside neuromonitoring (NM) predominantly consisted of transcranial Doppler
      sonography (94 %), electroencephalography (92 %) and measurement of intracranial
      pressure (ICP) (90 %), and was installed if patients had or were threatened by
      elevated ICP (86 %), had specific diseases like subarachnoid hemorrhage (51 %) or
      were comatose (35 %). Although mean trigger values for interventions complied
      with guidelines or wide-spread customs, individual trigger values varied widely,
      e.g., for hyperglycemia (maximum blood glucose between 120 and 250 mg/dl) or for
      anemia (minimum hemoglobin values between 5 and 10 g/dl). CONCLUSIONS: Although
      apparently aiming for standardization in neurocritical care, German NICUs show
      substantial differences in NM and monitoring-associated interventions. In terms
      of scoring and monitoring methods, German NICUs seem to be quite conservative.
      These survey results suggest a need of prospective and randomized interventional
      trials in neurocritical care to help define standards and target values.

PMID- 23979796
TI  - Predictors of late neurological deterioration after spontaneous intracerebral
      hemorrhage.
AB  - BACKGROUND: Although intracerebral hemorrhage (ICH) is a common form of
      cerebrovascular disease, little is known about factors leading to neurological
      deterioration occurring beyond 48 h after hematoma formation. The purpose of this
      study was to characterize the incidence, consequences, and associative factors of
      late neurological deterioration (LND) in patients with spontaneous ICH. METHODS:
      Using the Duke University Hospital Neuroscience Intensive Care Unit database from
      July 2007 to June 2012, a cohort of 149 consecutive patients with spontaneous
      supratentorial ICH met criteria for analysis. LND was defined as a decrease of
      two or more points in Glasgow Coma Scale score or death during the period from 48
      h to 1 week after ICH symptom onset. Unfavorable outcome was defined as a
      modified Rankin Scale score of >2 at discharge. RESULTS: Forty-three subjects
      (28.9 %) developed LND. Logistic regression models revealed hematoma volume (OR =
      1.017, 95 % CI 1.003-1.032, p = 0.019), intraventricular hemorrhage (OR = 2.519,
      95 % CI 1.142-5.554, p = 0.022) and serum glucose on admission (OR = 2.614, 95 %
      CI 1.146-5.965, p = 0.022) as independent predictors of LND. After adjusting for
      ICH score, LND was independently associated with unfavorable outcome (OR = 4.000,
      95 % CI 1.280-12.500, p = 0.017). In 65 subjects with follow-up computed
      tomography images, an increase in midline shift, as a surrogate for cerebral
      edema, was independently associated with LND (OR = 3.822, 95 % CI 1.157-12.622, p
      = 0.028). CONCLUSIONS: LND is a common phenomenon in patients with ICH; further,
      LND appears to affect outcome. Independent predictors of LND include hematoma
      volume, intraventricular hemorrhage, and blood glucose on admission. Progression
      of perihematomal edema may be one mechanism for LND.

PMID- 23979798
TI  - Well connected: pharmacy education and the humanities.
AB  - Traditional pharmacy education emphasizes the biological processes of diseases
      and their pharmacological treatments. While the intense focus on biomedical
      aspects of disease is vital to educating pharmacy students, this focus is often
      insufficient in conveying what patients experience. The humanities, however,
      offer powerful characterizations of the disease experience for individuals as
      well as its impact on the human condition more generally. In this essay, I
      describe how using literary texts with pharmacy students provides them with a
      fuller appreciation of what patients face with their diseases. The goal of this
      endeavor is to make students more effective as pharmacists in detecting and
      responding to their patients' problems and needs by connecting their biomedical
      knowledge to depictions and meanings of illness experiences. 

PMID- 23979799
TI  - The faces of injustice : comment on "moral distress in uninsured health care" by
      Anita Nivens and Janet Buelow.

PMID- 23979800
TI  - Characterisation of class I and II alpha-mannosidases from Drosophila
      melanogaster.
AB  - Homology searches indicated that up to five class I alpha-mannosidases
      (glycohydrolase family 47) and eight class II alpha-mannosidases (glycohydrolase
      family 38) are encoded by the fruitfly (Drosophila melanogaster) genome. Selected
      example mannosidases were expressed in secreted form using the yeast Pichia
      pastoris. A number of characteristics of these enzymes were determined with p
      nitrophenyl-alpha-mannoside as substrate; particularly striking were the low
      optima (pH 5) of three class II mannosidases most closely related to known
      lysosomal mannosidases and the distinct Co(II)-requirement of a mannosidase
      previously named ManIIb. Some of the recombinant mannosidases were demonstrably
      active towards oligomannosidic glycans, specifically, the Co(II)-requiring
      ManIIb, two 'acidic' mannosidases and the class I mas-1 mannosidase. Other than
      previous characterisations of the well-known Golgi mannosidase II, this is the
      first study summarising various properties of recombinant mannosidases from the
      fruitfly.

PMID- 23979801
TI  - A new preclinical approach for treating chronic osteomyelitis induced by
      Staphylococcus aureus: in vitro and in vivo study on photodynamic antimicrobial
      therapy (PAmT).
AB  - Osteomyelitis is an acute or chronic inflammation in the marrow spaces in the
      superficial or cortical bone, and can be associated with bacterial or fungal
      infections. Chronic osteomyelitis represents a major health problem due to its
      difficult treatment and increased morbidity. Photodynamic antimicrobial therapy
      (PAmT) is a treatment based on a cytotoxic photochemical reaction in which a
      bright light produced by a laser system and an active photosensitizer absorbed by
      cells leads to a process of activation that induces a series of metabolic
      reactions that culminates a bacterial killing. The aim of the present randomized
      study was to evaluate, by in vitro and in vivo microbiological analysis, the
      effects of PAmT on tibial surgical bone defects in rats infected by
      Staphylococcus aureus using bacterial counts carried out immediately and after 30
      days after treatment as outcome measure. In the preliminary in vitro study, a
      diode laser (lambda660 nm; 40 mW; phi = 0.4 cm(2); 5 or 10 J/cm(2)) and 5, 10,
      and 15 MUg/mL toluidine blue were tested, and the best parameter was chosen for
      the in vivo study. The concentration of 5 MUg/mL was selected to perform the
      decontamination of S. aureus-infected tibial bone defects in rats. The findings
      were subjected to statistical analysis. For all PAmTs groups, with the different
      concentrations, treatment showed significant reductions (p < 0.001) in the amount
      of bacteria. The in vivo study PAmT group presented a bacterial reduction of
      97.4% (p < 0.001). The PAmT using toluidine blue was effective in reducing the
      number of S. aureus in both in vitro and in vivo studies.

PMID- 23979804
TI  - Sore nipples in breastfeeding mothers: causes and treatments.

PMID- 23979805
TI  - Compounding for Investigational Studies: The Experience of Ken Hughes,RPh.

PMID- 23979802
TI  - Raman spectroscopy detection of molecular changes associated with two
      experimental models of osteoarthritis in rats.
AB  - The aim of the present study was to evaluate the feasibility of applying Raman
      spectroscopy in probing the molecular changes in terms of collagen deposition and
      tissue remodeling associated with two well-established experimental models of
      osteoarthritis (OA) in knee of rats. In order to evaluate alterations in the
      articular surface area, the menisci-covered tibial region was assessed into three
      groups as follows: control (joint preserved) and two models of experimental knee
      OA: collagenase-induced model (n = 8) and treadmill exercise-induced model (n =
      8). Each group was examined for molecular changes using spectral parameters
      related to cartilage, subchondral bone, and bone tissues. A significant increase
      of Raman ratios related to mineralization and tissue remodeling was found (p <
      0.05), suggesting that both models were successful for inducing OA in rats. The
      significantly lower phenylalanine content and higher crystallinity in the
      treadmill exercise-induced model of OA than collagenase-induced model of OA (p <
      0.05) indicated that the OA pathogenesis was model-dependent. Thus, this work
      suggests that the Raman spectroscopy technique has potential for the diagnosis
      and detection of cartilage damage and monitoring of subchondral bone and bone in
      OA pathogenesis at the molecular level. 

PMID- 23979806
TI  - Single-patient trials, extemporaneously compounded products and pharmaceutical
      care.

PMID- 23979808
TI  - Quality-control analytical methods: specific-gravity determinations of liquids
      and semisolids.

PMID- 23979807
TI  - Basics of compounding for dry-skin conditions.

PMID- 23979809
TI  - Pharmacokinetics in Healthy Volunteers of Sumatriptan 25-mg Oral Tablet Versus 25
      mg Extemporaneous Suppository.
AB  - The pharmacokinetics of an extemporaneous 25-mg suppository formulation of
      sumatriptan were compared to those of the marketed 25-mg oral tablet. Sixteen
      healthy volunteers enrolled in this open-label, two-way crossover study. Fifteen
      subjects completed the study. The pharmacokinetics of the suppository and the
      oral tablet were significantly different. Tmax was observed at 0.5 hours in 12 of
      15 subjects with the extemporaneous suppository, compared with the range of 0.75
      hours to 1.5 hours in 13 of 15 subjects with the oral tablet. The mean Cmax and
      area under the plasma concentration time curve were 5.4-fold and fourfold greater
      for the suppository than for the oral tablet. Both formulations were well
      tolerated, with mild headache experienced in only three subjects. Based upon its
      pharmacokinetic profile, the extemporaneous suppository may represent a useful
      alternative therapeutic administartion route for some patients. 

PMID- 23979810
TI  - Stability of two concentrations of tiagabine in an extemporaneously compounded
      suspension.
AB  - The short-term stability of two different concentrations of extemporaneously
      compounded tiagabine suspensions was studied. Six bottles each of 6-mg/mL and 2
      mg/mL suspensions were compounded using commercially available 16-mg tiagabine
      tablets in a 1:1 mixture of Ora-Sweet and Ora-Plus. For each concentration, three
      bottles were stored in the dark in a stability chamber at 23 to 25 deg C, and
      three were stored in the dark in a refrigerator at 3 to 5 deg C, for 61 days. The
      stability of tiagabine in each of the concentrations and environmental conditions
      was determined after preparation and at 7, 14, 28, 42, and 61 days by means of a
      high-performance liquid chromatographic method, which involved a reverse-phase
      column, a gradient mobile phase containing acetonitrile and aqueous phosphoric
      acid at a flow rate of 2.75mL/minute. Detection was carried out by an
      ultravioldet spetrophotometer at 254 nm. The drug tiagabine, the internal
      standard (propylparaben) and degradant eluted at 8.4, 8.6, and 9.9 minutes,
      respectively. The high-performance liquid chromatographic validation involved
      limit of detection, limit of quantitation, accuracy and precision and interday
      and intraday variation. There was no appearance of degradation products in eiher
      concentration at any time. The suspensions stored at 23 to 25 deg C became
      slightly discolord after day 30 , turning slightly gray from blue. However, this
      change could not be attributed to tiagabine degradation. The refrigerated
      suspensions were found to be stable (retention of 90% potency) up to 40 days. The
      6-mg/mL suspensions were stable up to the study period of 61 days; however, the 2
      mg/mL suspension at 3 to 5 deg C showed a potency of 87.7% on day 61 of the
      study. Extemporaneously compounded liquid oral preparations of tiagabine 6mg/mL
      in a 1:1 mixture of Ora-Plus and Ora-Sweet were stable for 61 days at 23 to 25
      deg C and 3 to 5 deg C. The extemporaneously compounded liquid oral preparations
      of tiagabine 2mg/mL in a 1:1 mixture of Ora-Plus and Ora-Sweet were stable for 61
      days at 23 to 25 deg C and for 40 days at 3 to 5 deg C. 

PMID- 23979811
TI  - Patient Interest in Pharmacist-Provided Menopause and Hormone Replacement Therapy
      consultations.
AB  - Many women experience unpleasant symptoms as they go through menopause. As they
      seek ways to help improve their quality of life, they can benefit from
      consultations with pharmacists that can help them understand and overcome their
      problems with menopause and hormone replacement therapy. The purpose of this
      study was to assess patients' experiences with menopause and hormone replacement
      therapy and to assess their interest in pharmacist-provided consultations. Women
      who were using medications to treat menopause were recruited by their pharmacists
      through convenience sampling. A self-administered survey was used to address the
      study objectives. Of the total number of surveys distributed (n=500), 203 were
      returned, resulting in a response rate of 41%. Before starting hormone
      replacement therapy, responsdents reported that they had experienced mood swings,
      loss of libido, night sweats and hot flashes at least half the time. The most
      common symptoms experienced after starting hormone replacement therapy were loss
      of libido and vaginal dryness, which were experienced sometimes up to half the
      time. Respondents indicated that they used their pharamcists most often as
      information sources for menopause- and hormone replacement therapy-related
      issues. Respondents also indicated that they would be very likely to seek help
      from a pharmacist and that they would pay, on average, $42.07 (standard deviation
      [SD] =$30.27) per half-hour for consultations, resulting in a 50% improvement in
      their symptoms, and $65.60 (SD = $26.60 per half-hour for consultations,
      resulting in a 100% improvement in their symptoms. The results indicate that
      patients regard pharmacists as their first source for menopause and hormone
      replacement therapy information and that they would be likely to use, as well as
      pay for, the services that pharmacists provide. The results of this study may be
      helpful to pharmacists who are considering providing menopause and hormone
      replacement therapy counseling services. 

PMID- 23979812
TI  - Physicochemical study of a novel chimeric chitinase with enhanced binding
      ability.
AB  - Chitinases are slow-reacting but important enzymes as they are anticipated to
      have diverse applications. The role of a chitin-binding domain (ChBD) in
      enhancing the quality of binding is essential information for purposeful
      engineering of chitinases. The idea of making hybrid chitinases by fusing a known
      ChBD to a chitinase, which naturally lacks ChBD is of interest especially for bio
      controlling purposes. Therefore, in the present study, the ChBD of Serratia
      marcescens chitinase B was selected and fused to the fungal chitinase,
      Trichoderma atroviride Chit42. Both Chit42 and chemric Chit42 (ChC) showed
      similar activity towards colloidal chitin with specificity constants of 0.83 and
      1.07 min(-1), respectively, same optimum temperatures (40 degrees C), and similar
      optimum pH (4 and 4.5, respectively). In the presence of insoluble chitin, ChC
      showed higher activity (70%) and obtained a remarkably higher binding constant
      (700 times). Spectroscopic studies indicated that chimerization of Chit42 caused
      some structural changes, which resulted in a reduction of alpha-helix in ChC
      structure. Chemical and thermal stability studies suggested that ChC had a more
      stable structure than Chit42. Hill analysis of the binding data revealed mixed
      cooperativity with positive cooperativity governing at ChC concentrations below
      0.5 and above 2 uM in the presence of insoluble chitin. It is suggested that the
      addition of the ChBD to Chit42 affords structural changes which enhance the
      binding ability of ChC to insoluble chitin, improving its catalytic efficiency
      and increasing its thermal and chemical stability. 

PMID- 23979813
TI  - Cross-modal associations between vision, touch, and audition influence visual
      search through top-down attention, not bottom-up capture.
AB  - Recently, Guzman-Martinez, Ortega, Grabowecky, Mossbridge, and Suzuki (Current
      Biology : CB, 22(5), 383-388, 2012) reported that observers could systematically
      match auditory amplitude modulations and tactile amplitude modulations to visual
      spatial frequencies, proposing that these cross-modal matches produced automatic
      attentional effects. Using a series of visual search tasks, we investigated
      whether informative auditory, tactile, or bimodal cues can guide attention toward
      a visual Gabor of matched spatial frequency (among others with different spatial
      frequencies). These cues improved visual search for some but not all frequencies.
      Auditory cues improved search only for the lowest and highest spatial
      frequencies, whereas tactile cues were more effective and frequency specific,
      although less effective than visual cues. Importantly, although tactile cues
      could produce efficient search when informative, they had no effect when
      uninformative. This suggests that cross-modal frequency matching occurs at a
      cognitive rather than sensory level and, therefore, influences visual search
      through voluntary, goal-directed behavior, rather than automatic attentional
      capture. 

PMID- 23979814
TI  - Urine kidney injury molecule-1: a potential non-invasive biomarker for patients
      with renal cell carcinoma.
AB  - BACKGROUND: KIM-1 staining is upregulated in proximal tubule-derived renal cell
      carcinoma (RCC) including clear renal cell carcinoma and papillary renal cell
      carcinoma, but not in chromophobe RCC (distal tubular tumor). This study was
      designed to prospectively examine urine KIM-1 level before and 1 month after
      removal of renal tumors. PATIENTS AND DESIGN: A total of 19 patients were
      eventually enrolled in the study based on pre-operative imaging studies. Pre
      operative and follow-up (1 month) urine KIM-1 levels were measured. The urine KIM
      1 levels (uKIM-1) were then normalized to urine creatinine levels (uCr). Renal
      tumors were also stained for KIM-1 using immunohistochemical techniques. RESULTS:
      The KIM-1-negative staining group included 7 cases, and the KIM-1-positive group
      consisted of 12 cases. The percentage of KIM-1-positive staining RCC cells ranged
      from 10 to 100 %, and the staining intensity ranged from 1+ to 3+. In both
      groups, serum creatinine levels were both significantly elevated after
      nephrectomy. In the KIM-1-negative group, uKIM-1/uCr remained at a similar level
      before (0.37 +/- 0.1 ng/mg Cr) and after nephrectomy (0.32 +/- 0.01 ng/mg Cr).
      However, in the KIM-1-positive group, elevated uKIM-1/uCr at 1.20 +/- 0.31 ng/mg
      Cr was significantly reduced to 0.36 +/- 0.1 ng/mg Cr, which was similar to the
      pre-operative uKIM-1/uCr (0.37 +/- 0.1 ng/mg Cr) in the KIM-1-negative group.
      CONCLUSION: Our small but prospective study showed significant reduction in uKIM
      1/uCr after nephrectomy in the KIM-1 positive group, suggesting that urine KIM-1
      may serve as a surrogate biomarker for kidney cancer and a non-invasive pre
      operative measure to evaluate the malignant potential of renal masses.

PMID- 23979815
TI  - Psychometric assessment of the Persian version of the Ferrans and Powers 3.0
      index in hemodialysis patients.
AB  - BACKGROUND: This study aimed to assess the psychometric properties of the Persian
      version of the Ferrans and Powers 3.0 quality of life index (dialysis type) in
      patients receiving hemodialysis (HD) in order to describe their health-related
      quality of life (HRQOL). METHODS: The sample (n = 150) consisted of adult HD
      patients receiving HD for at least 6 months from the establishment of the study.
      A total of 88 men and 62 women, with an average age of 50.47, from Shiraz,
      southern Iran, were enrolled in this study. The questionnaire was translated into
      Persian language using back translation and bilingual techniques. Convergent,
      discriminant, and construct validity of the Ferrans and Powers 3.0 dialysis
      version was evaluated. To check the internal consistency of the data, Cronbach's
      alpha, which indicates the reliability of the data, was used for the entire
      questionnaire and for the subscales. RESULTS: The convergent and discriminant
      validity and success scaling rate for both sexes were 100 %. Cronbach's alpha was
      0.95 overall, which was greater than 0.7 for all the subscales except for the
      family subscale. Our results suggest that HD patients in southern Iran have
      higher HRQOL scores when compared with those in other countries. Despite the
      higher mean HRQOL score for men compared with women, men had significantly higher
      HRQOL scores only in the health and functioning subscale. There was no
      significant correlation between HD patients' HRQOL and educational level.
      CONCLUSION: The Persian version of Ferrans and Powers 3.0 has sufficient
      reliability and validity for measuring the quality of life of Persian-speaking HD
      patients. Female HD patients need more support and attention from family and
      society.

PMID- 23979816
TI  - Reflex anuria: an old concept with new evidence.
AB  - Reflex anuria (RA) was defined by Hull as cessation of urine output from both
      kidneys due to irritation or trauma to one kidney or its ureter, or severely
      painful stimuli to other organs. This is not a common concept among urologists or
      nephrologists even though it has been proposed for more than half a century. The
      phenomenon has not been thoroughly understood. But intrarenal arteriolar spasm
      and ureteral spasm have gained wide acceptance as the mechanisms of RA. The
      present review summarized papers published up to now on RA, in order to depict
      the general profile of the disease and to further elucidate the pathogenesis of
      RA. A classification system of RA was proposed as neurovascular reflex,
      ureterorenal reflex, radiated renovascular reflex, renoureteral reflex,
      ureteroureteral reflex and radiated ureteral reflex, based on the two assumed
      mechanisms and the stimulus' origins. All these types except renoureteral reflex
      had gained supporting evidence from animal experiments and/or clinical case
      reports. RA is a diagnosis of exclusion, only being considered after ruling out
      common and tangible etiologies such as ureteral calculi, acute tubular necrosis,
      renal vascular occlusion, hypovolemia, infection, etc. If the diagnosis has been
      established, treatment plan should be directed toward the mechanisms more than
      the causative factors. Abnormalities of the autonomic nerve system and congenital
      urogenital malformations incline people to RA. In summary, RA is a cessation of
      urine production caused by stimuli on kidney, ureter or other organs, through a
      mechanism of reflex spasm of intrarenal arterioles or ureters, leading to acute
      renal failure. It is a functional rather than parenchymal disease.

PMID- 23979819
TI  - PET-CT imaging in the diagnosis of coronary stent infection.

PMID- 23979817
TI  - Association of serum total testosterone concentration with skeletal muscle mass
      in men under hemodialysis.
AB  - PURPOSE: Although skeletal muscle wasting can occur in chronic kidney diseases,
      its relationship with the serum testosterone concentration remains uncertain.
      This study investigates the relationship between serum testosterone and skeletal
      muscle mass in men under hemodialysis (HD). METHODS: Sixty men aged between 41
      and 89 years undergoing HD for 15.0 +/- 8.1 years were enrolled for this study.
      The muscle areas of the thigh (TMA) and abdomen (AMA) were measured by computed
      tomography (CT), and the association between these muscle areas and serum total
      testosterone was examined with adjustment of age and other nutritional variables.
      RESULTS: The mean serum total testosterone in our HD patients (6.33 +/- 2.90
      ng/mL) was not lower than that of the Japanese general population, but showed a
      positive correlation with TMA (r = 0.39, p < 0.05), AMA (r = 0.52, p < 0.001),
      serum creatinine (r = 0.33, p < 0.05), and the creatinine generation rate (r =
      0.26, p < 0.05). Serum total testosterone was inversely correlated with age (r = 
      0.32, p < 0.05), CRP (r = -0.31, p < 0.05), and IL-6 (r = -0.24, p < 0.05). A
      multiple-regression analysis showed both serum total testosterone and age to be
      an independent determinant of the muscle mass in these patients. CONCLUSIONS:
      This study identified testosterone as a determinant of muscle mass in HD men.

PMID- 23979820
TI  - Comparison of ancillary ligand effects between 2,2'-bipyridine and 2-(2'
      pyridyl)phenyl in the linkage and bridging isomerism of 5-methyltetrazolato
      iridium(III) and/or rhodium(III) complexes.
AB  - Several new iridium(III) and rhodium(III) complexes bearing 5-methyltetrazolate
      (MeCN4(-)) have been prepared, and their structures in the crystals and in
      solution have been determined by X-ray analysis and by NMR spectroscopy,
      respectively. In the crystals of the mononuclear complexes, kappaN(2)
      coordination of MeCN4(-) was observed when the ancillary ligand was 2,2'
      bipyridine (bpy): [Cp*M(bpy)(MeCN4-kappaN(2))]PF6 (Cp* = eta(5)-C5Me5; M = Ir: 1
      and Rh: 2), while the corresponding complexes with 2-(2'-pyridyl)phenyl (ppy(-))
      were confirmed to have the kappaN(1)-coordination of MeCN4(-): [Cp*M(ppy)(MeCN4
      kappaN(1))] (M = Ir: 3 and Rh: 4). In solution, the Ir(III) complexes (1 and 3)
      were robust enough to maintain their molecular structures, but the Rh(III)
      complexes (2 and 4) existed as an equilibrium mixture of the kappaN(1)- and
      kappaN(2)-isomers. In addition to the Ir(III)-Ir(III) and Rh(III)-Rh(III)
      homodinuclear complexes bridged by MeCN4(-) (5-8), the corresponding
      heterodinuclear Ir(III)-Rh(III) complexes (9-12) were prepared using the
      mononuclear Ir(III) complexes (1 and 3) as precursors. The molecular structures
      of these dinuclear complexes were also characterised. Interestingly, both of the
      heterodinuclear complexes comprised of Cp*M(bpy)(2+) and Cp*M'(ppy)(+) fragments,
      [Cp*M(bpy)(MU-MeCN4)M'(ppy)Cp*](PF6)2 (M = Ir, M' = Rh: 10 and M = Rh, M' = Ir:
      11), exhibited selective crystallisation of a specific MU-kappaN(1)(M'
      ppy):kappaN(3)(M-bpy) isomer. In solution, the dinuclear complexes with a Rh
      N(MeCN4) bond and more than one positive charge (6 and 9-11) showed a
      dissociation equilibrium, while monocationic MeCN4-bridged complexes (7, 8 and
      12) were inactive for dissociation. Furthermore, the heterodinuclear complexes of
      9-12, as well as the Rh(III)-Rh(III) complex of 8, exhibited a bridging
      isomerisation, which would proceed via a eta(2):eta(2)-intermediate without
      dissociation of Cp*M(bpy or ppy) fragments.

PMID- 23979821
TI  - Introducing novel amorphous carbon nanoparticles as energy acceptors into a
      chemiluminescence resonance energy transfer immunoassay system.
AB  - A novel chemiluminescence resonance energy transfer (CRET) system for competitive
      immunoassay of biomolecules was developed by using novel amorphous carbon
      nanoparticles (CNPs) prepared from candle soot as energy acceptors. The CNPs were
      firstly prepared to bind with the antigen (Ag) for obtaining the nanocomposite
      CNP-Ag, and this obtained CNP-Ag was then reacted with the horseradish peroxidase
      labeled antibody (HRP-Ab) to assemble the CRET system. The luminol catalyzed by
      HRP serving as the energy donor for CNPs triggered the CRET phenomenon between
      luminol and CNPs, which led to the chemiluminescence signal decrease. Due to the
      competitive immunoreaction of the target antigen and the CNP-Ag, a part of the
      CNP-Ag was replaced from the HRP-Ab, and then resulted in a weaker interaction
      between luminol and CNPs. Thus the competitive immunoreaction led to a higher
      chemiluminescence emission. This CNP-based CRET system was successfully applied
      to detect the human IgG as a model analyte, and a linear range of 10-200 ng mL(
      1) and a detection limit of 1.9 ng mL(-1) (S/N = 3) were obtained. The results
      for real sample analysis demonstrated its application potential in some important
      areas such as clinical diagnosis. 

PMID- 23979822
TI  - Primary adenocarcinoma of jejunum: a case report.

PMID- 23979824
TI  - Clinical pharmacist service in the acute ward.
AB  - BACKGROUND: The majority of hospitalised patients have drug-related problems.
      Clinical pharmacist services including medication history, medication
      reconciliation and medication review may reduce the number of drug-related
      problems. Acute and emergency hospital services have changed considerably during
      the past decade in Denmark, and the new fast-paced workflows pose new challenges
      for the provision of clinical pharmacist service. OBJECTIVE: To describe and
      evaluate a method for a clinical pharmacist service that is relevant and fit the
      workflow of the medical care in the acute ward. SETTING: Acute wards at three
      Danish hospitals. METHODS: The clinical pharmacist intervention comprised
      medication history, medication reconciliation, medication review, medical record
      entries and entry of prescription templates into the electronic medication
      module. Drug-related problems were categorised using The PCNE Classification
      V6.2. Inter-rater agreement analysis was used to validate the tool. Acceptance
      rates were measured as the physicians' approval of prescription templates and
      according to outcome in the PCNE classification. MAIN OUTCOME MEASURE: Acceptance
      rate of the clinical pharmacists' interventions through the described method and
      inter-rater agreement using the PCNE classification for drug-related problems.
      RESULTS: During 17 months, 188 patients were included in this study (average age
      72 years and 55 % women). The clinical pharmacists found drug-related problems in
      85 % of the patients. In the 1,724 prescriptions, 538 drug-related problems were
      identified. The overall acceptance rate by the physicians for the proposed
      interventions was 76 % (95 % CI 74-78 %). There was a substantial inter-rater
      agreement when using the PCNE classification system. CONCLUSION: The methods for
      a clinical pharmacist service in the acute ward in this study have been
      demonstrated to be relevant and timely. The method received a high acceptance
      rate, regardless of no need for oral communication, and a substantial inter-rater
      agreement when classifying the drug-related problems.

PMID- 23979825
TI  - Angioedema with normal laboratory values: the next step.
AB  - When faced with a patient with recurrent swelling, a thorough laboratory
      evaluation to determine the underlying etiology ensues. When the laboratory work
      up is unrevealing, health care practitioners are frequently left in a quandary.
      This review will attempt to provide up-to-date information on how to approach the
      diagnosis and management of angioedema in a patient with normal laboratory
      values. The subtypes that will be reviewed in detail include: hereditary
      angioedema with normal C1 inhibitor (HAE with normal C1INH), drug-induced
      angioedema, and idiopathic angioedema. We present literature to aid the physician
      in the diagnosis and treatment of these disorders. 

PMID- 23979826
TI  - Cyclic dipeptides from rhabditid entomopathogenic nematode-associated Bacillus
      cereus have antimicrobial activities.
AB  - The cell free culture filtrate of Bacillus cereus associated with an
      entomopathogenic nematode, Rhabditis (Oscheius) sp. exhibited strong
      antimicrobial activity. The ethyl acetate extract of the bacterial culture
      filtrate was purified by silica gel column chromatography to obtain four
      bioactive compounds. The structure and absolute stereochemistry of these
      compounds were determined based on extensive spectroscopic analyses (FABMS, (1)H
      NMR, (13)C NMR, (1)H-(1)H COSY, (1)H-(13)C HMBC) and Marfey's method. The
      compounds were identified as cyclic dipeptides (CDPs): cyclo(L-Pro-L-Trp),
      cyclo(L-Leu-L-Val), cyclo(D-Pro-D-Met), and cyclo(D-Pro-D-Phe), respectively.
      Compounds recorded significant antibacterial activity against all the test
      bacteria (Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella
      pneumoniae, Escherichia coli, Pseudomonas aeruginosa and methicillin-resistant S.
      aureus) except cyclo(L-Leu-L-Val). Cyclo(L-Leu-L-Val) recorded activity only
      against Gram positive bacteria. Best antibacterial activity was recorded by
      cyclo(L-Pro-L-Trp) against S. aureus (4 MUg/ml). The four compounds were active
      against all the five fungi tested (Trichophyton rubrum, Aspergillus flavus,
      Candida albicans, Candida tropicalis and Cryptococcus neoformans) and the
      activity was compared with amphotericin B, the standard fungicide. The highest
      activity of 1 MUg/ml by cyclo(L-Pro-L-Trp) was recorded against T. rubrum, a
      human pathogen responsible for causing athlete's foot, jock itch, and ringworm.
      The activity of cyclo(L-Pro-L-Trp) against T. rubrum, C. neoformans and C.
      albicans were better than amphotericin B, the standard antifungal agent. To our
      knowledge, this is the first report of antifungal activity of CDPs against the
      human pathogenic fungi T. rubrum and C. neoformans. The four CDPs are nontoxic to
      healthy human cell line up to 200 MUg/ml. We conclude that the bacterium
      associated with entomopathogenic nematode is promising sources of natural
      antimicrobial secondary metabolites, which may receive greater benefit as
      potential sources of new drugs in the pharmaceutical industry.

PMID- 23979827
TI  - Antimicrobial effect and membrane-active mechanism of tea polyphenols against
      Serratia marcescens.
AB  - In this study, we investigated the antimicrobial effect of tea polyphenols (TP)
      against Serratia marcescens and examined the related mechanism. Morphology
      changes of S. marcescens were first observed by transmission electron microscopy
      after treatment with TP, which indicated that the primary inhibition action of TP
      was to damage the bacterial cell membranes. The permeability of the outer and
      inner membrane of S. marcescens dramatically increased after TP treatment, which
      caused severe disruption of cell membrane, followed by the release of small
      cellular molecules. Furthermore, a proteomics approach based on two-dimensional
      gel electrophoresis and MALDI-TOF/TOF MS analysis was used to study the
      difference of membrane protein expression in the control and TP treatment S.
      marcescens. The results showed that the expression of some metabolism enzymes and
      chaperones in TP-treated S. marcescens significantly increased compared to the
      untreated group, which might result in the metabolic disorder of this bacteria.
      Taken together, our results first demonstrated that TP had a significant growth
      inhibition effect on S. marcescens through cell membrane damage. 

PMID- 23979828
TI  - [Venous thromboembolism in adolescents associated with fourth-generation oral
      contraceptives].
AB  - Venous thromboembolism (VTE) is a rare, but feared adverse drug reaction of
      combined oral contraceptives. Modern oral contraceptives contain novel
      progestins, which are suspected of causing thrombotic events more frequently than
      well-known progestins. Drospirenone is one of those new fourth-generation
      progestins with antiandrogenic and antimineralocorticoid effects. Especially
      girls and young women do not only wish for contraception, but also for positive
      effects on skin and body weight. In the last decade, however, the safety of this
      progestin was often under discussion.A detailed literature search was conducted
      to obtain an overview of currently available data on the risk of VTE among girls
      and young women using drospirenone-containing contraceptives. It appears that
      drospirenone-containing contraceptives have a similar increase in risk as third
      generation oral contraceptives and antiandrogens. Compared to second-generation
      contraceptives containing the progestin levonorgestrel there is an approximate 2
      fold risk increase (1.0 to 2.8-fold) in women aged 10-55 years. Accurate data
      regarding the risk in the age group under 18 years are lacking. Nevertheless, the
      risk of VTE appears to be higher in young -women during the first months of
      treatment. Until more data for nov-el progestins are available and the safety
      profile is well defined well-studied second-generation oral contraceptives with
      low dose estrogen and better risk-benefit ratio should be preferred in young
      women. In any case, all patients should be comprehensively informed regarding the
      benefits and risks of each contraceptive method. 

PMID- 23979830
TI  - Bayesian Modeling of Enteric Virus Density in Wastewater Using Left-Censored
      Data.
AB  - Stochastic models are used to express pathogen density in environmental samples
      for performing microbial risk assessment with quantitative uncertainty. However,
      enteric virus density in water often falls below the quantification limit (non
      detect) of the analytical methods employed, and it is always difficult to apply
      stochastic models to a dataset with a substantially high number of non-detects,
      i.e., left-censored data. We applied a Bayesian model that is able to model both
      the detected data (detects) and non-detects to simulated left-censored datasets
      of enteric virus density in wastewater. One hundred paired datasets were
      generated for each of the 39 combinations of a sample size and the number of
      detects, in which three sample sizes (12, 24, and 48) and the number of detects
      from 1 to 12, 24 and 48 were employed. The simulated observation data were
      assigned to one of two groups, i.e., detects and non-detects, by setting values
      on the limit of quantification to obtain the assumed number of detects for
      creating censored datasets. Then, the Bayesian model was applied to the censored
      datasets, and the estimated mean and standard deviation were compared to the true
      values by root mean square deviation. The difference between the true
      distribution and posterior predictive distribution was evaluated by Kullback
      Leibler (KL) divergence, and it was found that the estimation accuracy was
      strongly affected by the number of detects. It is difficult to describe universal
      criteria to decide which level of accuracy is enough, but eight or more detects
      are required to accurately estimate the posterior predictive distributions when
      the sample size is 12, 24, or 48. The posterior predictive distribution of virus
      removal efficiency with a wastewater treatment unit process was obtained as the
      log ratio posterior distributions between the posterior predictive distributions
      of enteric viruses in untreated wastewater and treated wastewater. The KL
      divergence between the true distribution and posterior predictive distribution of
      virus removal efficiency also depends on the number of detects, and eight or more
      detects in a dataset of treated wastewater are required for its accurate
      estimation.

PMID- 23979829
TI  - There's risk, and then there's risk: The latest clinical prognostic risk
      stratification models in myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) include a diverse group of clonal hematopoietic
      disorders characterized by progressive cytopenias and propensity for leukemic
      progression. The biologic heterogeneity that underlies MDS translates clinically
      in wide variations of clinical outcomes. Several prognostic schemes were
      developed to predict the natural course of MDS, counsel patients, and allow
      evidence-based, risk-adaptive implementation of therapeutic strategies. The
      prognostic schemes divide patients into subgroups with similar prognosis, but the
      extent to which the prognostic prediction applies to any individual patient is
      more variable. None of these instruments was designed to predict the clinical
      benefit in relation to any specific MDS therapy. The prognostic impact of
      molecular mutations is being more recognized and attempts at incorporating it
      into the current prognostic schemes are ongoing.

PMID- 23979831
TI  - Electrophysiological evidence for preparatory reconfiguration before voluntary
      task switches but not cued task switches.
AB  - An unresolved issue in the task-switching literature is whether preparatory
      reconfiguration occurs before a change of task. In this study, we used event
      related potentials (ERPs) to determine whether preparatory reconfiguration occurs
      during two different task-switching procedures: voluntary and cued task
      switching. We focused on two ERP components that index different cognitive
      operations. The contingent negative variation (CNV) is a sensitive measure of a
      participant's preparedness to use a specific stimulus-response mapping. In
      contrast, the P3 indexes memory updating. We found a pronounced modulation of the
      CNV before voluntary task switches, but not before cued task switches. Instead,
      cued task switches were preceded by a larger P3, as compared with task
      repetitions. Our findings suggest that task set reconfiguration is carried out
      prior to voluntary task switches, whereas memory processes dominate cued task
      switches. 

PMID- 23979832
TI  - Down-regulation of HAI-1 is associated with poor-differentiation status of
      colorectal cancer.
AB  - Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a Kunitz-type
      serine protease inhibitor which is widely expressed in epithelial cells. The
      purpose of this study is to investigate the relationship between HAI-1 expression
      and differentiation status of colorectal epithelia. The expression of HAI-1 in
      clinical samples of both cancerous and normal colorectal tissues was evaluated by
      immunohistochemical staining. An in vitro epithelial differentiation model of
      Caco-2 cell was established, and the characteristics of differentiation of Caco-2
      cells were observed by transmission electron microscopy. The expression of HAI-1
      in Caco-2 cells at different differentiation stages was examined by western blot.
      Immunohistochemical staining of 52 human colorectal cancer tissues showed a
      definite correlation between HAI-1 expression and differentiation status: IHC
      score (mean +/- SE) of HAI-1 was higher for well- or moderately-differentiated
      colorectal cancer tissues than for poorly-differentiated colorectal cancer
      tissues, with significant differences in HAI-1 positive rate (P < 0.01 and P <
      0.05 for well-differentiated vs. poorly-differentiated and moderately
      differentiated vs. poorly-differentiated, respectively). Immunohistochemical
      staining of normal colorectal tissues showed positive HAI-1 expression in well
      differentiated epithelial cells whereas the under-differentiated crypt cells
      showed very weak HAI-1 staining signals. The result of western blot also showed
      the gradual increasing of HAI-1 expression during the process of Caco-2
      differentiation in vitro. HAI-1 expression correlates with the differentiation
      status of colorectal epithelia and could serve as a differentiation marker. 

PMID- 23979834
TI  - Phenanthrenes from Juncus effusus.
AB  - A chemical investigation of the EtOAc-soluble fraction from the ethanol extract
      of the medullae of Juncus effusus led to the isolation of three new 9,10
      dihydrophenanthrenes, juncuenins E-G (1-3); two new phenanthrenes,
      dehydrojuncuenins D-E (4-5); one new feruloylated glycoside (6); and one known
      9,10-dihydrophenanthrene (7). The structures of these compounds were determined
      by analyzing their spectroscopic data. Metabolites 1-4 and 7 were further
      evaluated for their in vitro cytotoxic activities against seven human cancer
      lines (A549, MCF-7, BEL-7402, HeLa, COLO205, BGC-823, and SK-OV-3). Among them,
      compound 1 exhibited weak cytotoxicity against MCF-7 and HeLa cell lines.
      Compound 7 showed moderate cytotoxicity against MCF-7 and HeLa cell lines, with
      IC50 values of 9.17 and 19.6 uM, respectively. 

PMID- 23979833
TI  - In vivo molecular imaging of apoptosis and necrosis in atherosclerotic plaques
      using microSPECT-CT and microPET-CT imaging.
AB  - PURPOSE: The purpose of this paper is to study molecular imaging of apoptosis and
      necrosis, two key players in atherosclerosis instability, using a multimodal
      imaging approach combining single photon emission computed tomography (SPECT),
      positron emission tomography (PET), and computed tomography (CT). PROCEDURES:
      Collar-induced carotid atherosclerosis ApoE knockout mice were imaged with
      (99m)Tc-AnxAF568 SPECT-CT to study apoptosis and sequentially with PET-CT
      following (124)I-Hypericin ((124)I-Hyp) injection to visualize necrosis. RESULTS:
      SPECT depicted increased (99m)Tc-AnxAF568 uptake in both atherosclerotic carotid
      arteries, whereas our data suggest that this uptake is not merely apoptosis
      related. Although PET of (124)I-Hyp was hampered by the slow blood clearance in
      atherosclerotic mice, (124)I-Hyp was able to target necrosis in the
      atherosclerotic plaque. CONCLUSION: Both (99m)Tc-AnxAF568 and (124)I-Hyp uptake
      are increased in atherosclerotic carotid vasculature compared to control
      arteries. While apoptosis imaging remains challenging, necrosis imaging can be
      feasible after improving the biodistribution characteristics of the probe.

PMID- 23979835
TI  - Derivation of pre-oligodendrocytes from human endometrial stromal cells by using
      overexpression of microRNA 338.
AB  - MicroRNAs have a critical role in oligodendrocyte development including cell
      proliferation, differentiation, and myelin formation. MicroRNA 338 (miR-338) is
      necessary to promote oligodendrocyte differentiation by repressing negative
      regulators of oligodendrocyte differentiation. Oligodendrocytes (OLs) are
      responsible for myelin sheath synthesis around nerve fibers in the central
      nervous system (CNS) that form the myelin sheath of axons. Human endometrial
      derived stromal cells (hEnSCs) are a new source of mesenchymal-like stem cells
      for cell replacement therapy. The hEnSCs, after treating with fibroblast growth
      factor 2/epidermal growth factor (20 ng/mL) and platelet-derived growth factor
      (PDGF)-AA (10 ng/mL) for 12 days, were divided in two groups: in the first group,
      the cells were treated by triiodothyronine (T3), and in the second group, the
      cells were infected by miR-338-green fluorescent protein-expressing lentiviruses.
      Six days after infection, the cells were collected and analyzed for the
      expression of stage-specific markers Nestin, microtubule-associated protein 2,
      neurofilament-L, oligodendrocyte lineage transcription factor, SRY-box containing
      gene 10, PDGF receptor alpha, 2',3'-cyclic nucleotide 3' phosphodiesterase, A2B5,
      O4, and myelin basic protein by immunocytochemistry and quantitative reverse
      transcription PCR. Result showed that in the infected cells, the expression of
      pre-oligodendrocyte markers was higher than that of T3-treated cells. The EnSCs
      can differentiate to oligodendrocyte cells by the overexpression of miR-338, and
      these cells can be used as a unique source for cell therapy of neurodegenerative
      disease.

PMID- 23979836
TI  - HIF-1alpha involves in neuronal apoptosis after traumatic brain injury in adult
      rats.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha), a well-identified hypoxia-related
      protein, is involved in regulating the biological functions of various cell types
      including neurons. The traditional biological function of HIF-1alpha is promoting
      the transcription of some pro-survival genes when exposing to low oxygen
      conditions. Meanwhile, some studies also point out that HIF-1alpha shows the
      detrimental role in several central nervous system (CNS) disorders. Up to now,
      the knowledge of HIF-1alpha function in CNS is still limited. To investigate
      whether HIF-1alpha is involved in CNS impairment and repair, we employed a
      traumatic brain injury model in adult rats. Upregulation of HIF-1alpha was
      observed in the injured brain cortex by western blot analysis and
      immunohistochemistry staining. Terminal deoxynucleotidyl transferase deoxy-UTP
      nick-end labeling (TUNEL) and 4',6-diamidino-2-phenylindole (DAPI) staining
      suggested that HIF-1alpha was relevant to neuronal apoptosis after brain injury.
      In addition, glutamate excitotoxic model of primary cortex neurons was introduced
      to further investigate the role of HIF-1alpha in neuronal apoptosis; the result
      implied HIF-1alpha was associated with the regulation of p53 and BNIP3 in the
      apoptotic neurons. Based on our data, we suggested that HIF-1alpha might play an
      important role in neuronal apoptosis after traumatic brain injury in rat, which
      might also provide a basis for the further study on its role in regulating the
      transcription of target genes in apoptotic neurons, and might gain a novel
      strategy for the clinical therapy for traumatic brain injury. 

PMID- 23979837
TI  - Kainate receptor RNA editing is markedly altered by acute spinal cord injury.
AB  - We have previously observed changes in the RNA editing of AMPA receptors after
      acute spinal cord injury (SCI); this implies that post-transcriptional
      modifications are capable of affecting the physiological properties of glutamate
      receptor channels and related signal transduction in this neurodegenerative
      condition. Here, we report that the editing of the ionotropic KAR is markedly
      decreased at both GluK1 and GluK2 Q/R sites in the epicenter of the lesion and
      with distinct magnitude and kinetics also in the caudal and rostral portions of
      the injured cord. These effects are persistent, being observed as late as 30 days
      after lesioning. In addition, also the I/V and Y/C sites of GluK2 were severely
      affected after SCI. These findings add novel information to the relevance of
      editing of glutamate receptors following acute SCI, thus expanding the recently
      emerged role of post-transcriptional mechanisms under these experimental
      conditions.

PMID- 23979838
TI  - Parkinson's disease-associated DJ-1 mutations increase abnormal phosphorylation
      of tau protein through Akt/GSK-3beta pathways.
AB  - Hyperphosphorylated tau protein is the main component of neurofibrillary tangles
      found in Alzheimer's disease and Parkinson's disease (PD). Mutations in DJ-1 have
      been identified as the causative gene for Parkinson's disease 7 (PARK7)-linked
      PD. DJ-1L166P and DJ-1D149A, two types of DJ-1 mutations, are most commonly
      studied as the loss-of-function mutations responsible for early-onset familial
      PD. Whether mutations in DJ-1 result in tauopathy is as yet unknown. In this
      study, we found that the L166P and D149A mutant isoforms of DJ-1 associated with
      familial PD cause tau phosphorylation at Ser202, Ser262, and PHF1 (396/404) sites
      in neuroblastoma 2a cells. Glycogen synthase kinase (GSK)-3beta phosphorylation
      at serine 9 (Ser9) decreases around 50 % in DJ-1L166P- or DJ-1D149A-transfected
      cells, while there is no change in total levels of GSK-3beta. Our results also
      indicate that overexpression of DJ-1L166P or DJ-1D149A leads to a significant
      decrease in the level of phosphorylation of Akt at Thr308, which plays a critical
      role in phosphorylating GSK-3beta at Ser9 and inhibiting its kinase activity.
      Importantly, insulin, the activator for Akt, effectively attenuates the reduced
      phosphorylation level of GSK-3beta at Ser9 induced by DJ-1L166P. Neither the
      expression of cyclin-dependent kinase 5 nor the level of PP2A activity was found
      to have changed, suggesting that the familial PD-associated DJ-1L166P and DJ
      1D149A mutations increase tau phosphorylation by increasing the activity of GSK
      3beta. Finally, we found that administration of lithium chloride, a well-known
      GSK-3beta inhibitor, resulted in decreased levels of phosphorylated tau in DJ
      1L166P-transfected cells. 

PMID- 23979839
TI  - The compact mutation of myostatin causes a glycolytic shift in the phenotype of
      fast skeletal muscles.
AB  - Myostatin is an important negative regulator of skeletal muscle growth. The
      hypermuscular Compact (Cmpt) mice carry a 12-bp natural mutation in the myostatin
      propeptide, with additional modifier genes being responsible for the phenotype.
      Muscle cellularity of the fast-type tibialis anterior (TA) and extensor digitorum
      longus (EDL) as well as the mixed-type soleus (SOL) muscles of Cmpt and wild-type
      mice was examined by immunohistochemical staining of the myosin heavy chain (MHC)
      proteins. In addition, transcript levels of MHC isoforms were quantified by qPCR.
      Based on our results, all investigated muscles of Cmpt mice were significantly
      larger compared with that of wild-type mice, as characterized by fiber
      hyperplasia of different grades. Fiber hypertrophy was not present in TA;
      however, EDL muscles showed specific IIB fiber hypertrophy while the (I and IIA)
      fibers of SOL muscles were generally hypertrophied. Both the fast TA and EDL
      muscles of Cmpt mice contained significantly more glycolytic IIB fibers
      accompanied by a decreased number of IIX and IIA fibers; however, this was not
      the case for SOL muscles. In summary, despite the variances found in muscle
      cellularity between the different myostatin mutant mice, similar glycolytic
      shifts were observed in Cmpt fast muscles as in muscles from myostatin knockout
      mice. 

PMID- 23979840
TI  - Expression of asialoglycoprotein receptor 1 in human hepatocellular carcinoma.
AB  - Human hepatocellular carcinoma (HCC) is the fifth most common cancer in the
      world. Currently, surgical resection is the only effective treatment for HCC if
      the tumor is resectable. Small molecule, biologics and siRNA anti-cancer drugs
      have been explored for the treatment of HCC. Selective targeting to tumor tissue
      rather than normal liver in HCC patients is still a challenge. Galactosamine
      mediated targeting delivery of anti-cancer drugs in the liver has been tested
      because its receptor, asialoglycoprotein receptor 1 (ASGPR1), is expressed in the
      liver and not in other human tissues. We examined ASGPR1 expression levels by
      immunohistochemistry in HCC with different grades. Guidance for a targeting
      delivery strategy for anti-cancer drugs to HCC is suggested in this report. 

PMID- 23979841
TI  - Neuron-derived IgG protects neurons from complement-dependent cytotoxicity.
AB  - Passive immunity of the nervous system has traditionally been thought to be
      predominantly due to the blood-brain barrier. This concept must now be revisited
      based on the existence of neuron-derived IgG. The conventional concept is that
      IgG is produced solely by mature B lymphocytes, but it has now been found to be
      synthesized by murine and human neurons. However, the function of this endogenous
      IgG is poorly understood. In this study, we confirm IgG production by rat
      cortical neurons at the protein and mRNA levels, with 69.0 +/- 5.8% of cortical
      neurons IgG-positive. Injury to primary-culture neurons was induced by complement
      leading to increases in IgG production. Blockage of neuron-derived IgG resulted
      in more neuronal death and early apoptosis in the presence of complement. In
      addition, FcgammaRI was found in microglia and astrocytes. Expression of FcgammaR
      I in microglia was increased by exposure to neuron-derived IgG. Release of NO
      from microglia triggered by complement was attenuated by neuron-derived IgG, and
      this attenuation could be reversed by IgG neutralization. These data demonstrate
      that neuron-derived IgG is protective of neurons against injury induced by
      complement and microglial activation. IgG appears to play an important role in
      maintaining the stability of the nervous system. 

PMID- 23979842
TI  - Disrupting hypothalamic glucocorticoid receptors causes HPA axis hyperactivity
      and excess adiposity.
AB  - The glucocorticoid receptor (GR) regulates hypothalamic-pituitary-adrenal (HPA)
      axis activity during the stress response. The paraventricular nucleus (PVN) is a
      major site of negative feedback to coordinate the degree of the HPA axis activity
      with the magnitude of the exposed stressor. To define the function of endogenous
      PVN GR, we used Cre-loxP technology to disrupt different GR exons in Sim1
      expressing neurons of the hypothalamus. GR exon 2-deleted mice (Sim1Cre
      GRe2Delta) demonstrated 43% loss of PVN GR compared with an 87% GR loss in exon 3
      deleted mice (Sim1Cre-GRe3Delta). Sim1Cre-GRe3Delta mice display stunted growth
      at birth but develop obesity in adulthood and display impaired stress-induced
      glucose release. We observed elevated basal and stress-induced corticosterone
      levels in Sim1Cre-GRe3Delta mice, compared with control and Sim1Cre-GRe2Delta
      mice, and impaired dexamethasone suppression, indicating an inability to
      negatively regulate corticosterone secretion. Sim1Cre-GRe3Delta mice also showed
      increased CRH mRNA in the PVN, increased basal plasma ACTH levels, and reduced
      locomotor behavior. We observed no differences in Sim1Cre-GRe2Delta mice compared
      with control mice in any measure. Our behavioral data suggest that GR deletion in
      Sim1-expressing neurons has no effect on anxiety or despair-like behavior under
      basal conditions. We conclude that loss of PVN GR results in severe HPA axis
      hyperactivity and Cushing's syndrome-like phenotype but does not affect anxiety
      and despair-like behaviors. 

PMID- 23979843
TI  - AMPK regulates ER morphology and function in stressed pancreatic beta-cells via
      phosphorylation of DRP1.
AB  - Experimental lipotoxicity constitutes a model for beta-cell demise induced by
      metabolic stress in obesity and type 2 diabetes. Fatty acid excess induces
      endoplasmic reticulum (ER) stress, which is accompanied by ER morphological
      changes whose mechanisms and relevance are unknown. We found that the GTPase
      dynamin-related protein 1 (DRP1), a key regulator of mitochondrial fission, is an
      ER resident regulating ER morphology in stressed beta-cells. Inhibition of DRP1
      activity using a GTP hydrolysis-defective mutant (Ad-K38A) attenuated fatty acid
      induced ER expansion and mitochondrial fission. Strikingly, stimulating the key
      energy-sensor AMP-activated protein kinase (AMPK) increased the phosphorylation
      at the anti-fission site Serine 637 and largely prevented the alterations in ER
      and mitochondrial morphology. Expression of a DRP1 mutant resistant to
      phosphorylation at this position partially prevented the recovery of ER and
      mitochondrial morphology by AMPK. Fatty acid-induced ER enlargement was
      associated with proinsulin retention in the ER, together with increased
      proinsulin/insulin ratio. Stimulation of AMPK prevented these alterations, as
      well as mitochondrial fragmentation and apoptosis. In summary, DRP1 regulation by
      AMPK delineates a novel pathway controlling ER and mitochondrial morphology,
      thereby modulating the response of beta-cells to metabolic stress. DRP1 may thus
      function as a node integrating signals from stress regulators, such as AMPK, to
      coordinate organelle shape and function. 

PMID- 23979844
TI  - Research resource: global identification of estrogen receptor beta target genes
      in triple negative breast cancer cells.
AB  - Breast cancers that are negative for estrogen receptor alpha (ERalpha),
      progesterone receptor, and human epidermal growth factor receptor 2 are known as
      triple-negative breast cancers (TNBC). TNBCs are associated with an overall poor
      prognosis because they lack expression of therapeutic targets like ERalpha and
      are biologically more aggressive. A second estrogen receptor, ERbeta, has been
      found to be expressed in 50% to 90% of ERalpha-negative breast cancers, and
      ERbeta expression in TNBCs has been shown to correlate with improved disease-free
      survival and good prognosis. To elucidate the role of ERbeta in regulating gene
      expression and cell proliferation in TNBC cells, the TNBC cell line MDA-MB-468
      was engineered with inducible expression of full-length ERbeta. In culture,
      ERbeta expression inhibited cell growth by inducing a G1 cell cycle arrest, which
      was further enhanced by 17beta-estradiol treatment. In xenografts, ERbeta
      expression also inhibited tumor formation and growth, and 17beta-estradiol
      treatment resulted in rapid tumor regression. Furthermore, genomic RNA sequencing
      identified both ligand-dependent and -independent ERbeta target genes, some of
      which were also regulated by ERbeta in other TNBC cell lines and correlated with
      ERbeta expression in a cohort of TNBCs from the Cancer Genome Atlas Network.
      ERbeta target genes were enriched in genes that regulate cell death and survival,
      cell movement, cell development, and growth and proliferation, as well as genes
      involved in the Wnt/beta-catenin and the G1/S cell cycle phase checkpoint
      pathways. In addition to confirming the anti-proliferative effects of ERbeta in
      TNBC cells, these data provide a comprehensive resource of ERbeta target genes
      and suggest that ERbeta may be targeted with ligands that can stimulate its
      growth inhibitory effects. 

PMID- 23979846
TI  - Effects of conditions of an experimental model to evaluate methods of electric
      fence strand addition to barbed-wire fence to contain goats.
AB  - Growing meat goats of 4 types (Boer and Spanish of both wethers and doelings)
      were used to evaluate conditions for a method of testing efficacy of electric
      fence strand additions to barbed-wire fence used for cattle to also contain
      goats. Animals were allocated to 8 sets, with each set consisting of 5 groups.
      There was 1 goat of each of the 4 types in a group. One side of five 2.4- * 3.7-m
      evaluation pens consisted of barbed-wire strands at 30, 56, 81, 107, and 132 cm
      from the ground. Evaluation pens were adjacent to a pasture with abundant
      vegetation. Fence treatments (FT) were electrified strands (6 kV) at 15- and 43-
      (LowHigh), 15- and 23- (LowMed), 15- (Low), 23- (Med), and 43-cm (High), where
      Low, Med, and High abbreviations are for low, medium, and high heights from the
      ground, respectively. For adaptation, there were 4-wk and sequential exposures to
      evaluation pens: wk 1, no electric strands; wk 2, 1 strand at 0 kV; wk 3,
      LowHigh; and wk 4, LowHigh. There were 6 periods for measurements, each separated
      by 1 wk. During the 1-wk intervals on pasture, sets were exposed to 1 interval
      treatment without and another with 2 electric strands (6 kV) positioned next to
      supplement troughs, to potentially affect familiarity with electrified strands
      and influence subsequent behavior. All animal sets were used for measurements in
      period 1 in a completely randomized design (CRD). Four sets were also used in 4
      wk subsequent measurement periods for a 5 * 5 Latin square (LS). All animal sets
      were exposed to the same FT in period 6 as in period 1. Behavior in evaluation
      pens was observed for 1 h with a video surveillance system in the 6 periods.
      There were no effects of gender and few and minor effects of preliminary and
      interval treatments. The percentage of animals that exited evaluation pens
      differed (P < 0.05) among FT, with the CRD approach in period 1 (25%, 47%, 38%,
      66%, and 84%; SEM = 8.0) and with repeated measures in periods 1 and 6 (6%, 22%,
      22%, 63%, and 81% for LowHigh, LowMed, Low, High, and Med, respectively; SEM =
      4.9), and between breeds in periods 1 (34% and 70%) and 1 and 6 (28% and 50% for
      Boer and Spanish, respectively). For the LS approach, FT affected exit (31%, 23%,
      16%, 35%, and 30%; SEM = 5.3) and breeds differed (P < 0.05), as well (12% and
      43%). Exit decreased as period advanced (60%, 35%, 23%, 10%, and 8%, for 1, 2, 3,
      4, and 5, respectively; SEM = 5.3). In conclusion, breed should be considered in
      the model being developed. A LS approach was not suitable, but a CRD experiment
      after these adaptation procedures appears promising.

PMID- 23979845
TI  - Research resource: progesterone receptor targetome underlying mammary gland
      branching morphogenesis.
AB  - Progesterone (P4)-activated progesterone receptors (PRs) play an essential role
      in driving pregnancy-associated mammary ductal side-branching morphogenesis and
      alveologenesis. However, the global cistromic and transcriptome responses that
      are required to elicit P4-dependent branching morphogenesis have not been
      elucidated. By combining chromatin immunoprecipitation followed by deep
      sequencing to identify genome-wide PR-binding sites in PR-positive luminal
      epithelial cells with global gene expression signatures acutely regulated by PRs
      in the mammary gland, we have identified a mammary epithelial PR targetome
      associated with active P4-dependent branching morphogenesis in vivo. We
      demonstrate that P4-induced side-branching is initiated by epithelial cell
      rearrangement into a multilayered epithelium that sprouts laterally from
      quiescent ducts via a mechanism requiring P4-dependent activation of Rac-GTPase
      signaling. We identify effectors of Rac-GTPases as direct transcriptional targets
      of PRs, and we demonstrate that disruption of the P4-activated Rac-GTPase
      signaling axis is sufficient to eliminate P4-dependent side-branching. Our data
      reveal that the molecular mediators of P4-dependent ductal side-branching overlap
      with those implicated in breast cancer. 

PMID- 23979847
TI  - Enhanced reduction of phenol content and toxicity in olive mill wastewaters by a
      newly isolated strain of Coriolopsis gallica.
AB  - The search for novel microorganisms able to degrade olive mill wastewaters (OMW)
      and withstand the toxic effects of the initially high phenolic concentrations is
      of great scientific and industrial interest. In this work, the possibility of
      reducing the phenolic content of OMW using new isolates of fungal strains
      (Coriolopsis gallica, Bjerkandera adusta, Trametes versicolor, Trichoderma
      citrinoviride, Phanerochaete chrysosporium, Gloeophyllum trabeum, Trametes
      trogii, and Fusarium solani) was investigated. In vitro, all fungal isolates
      tested caused an outstanding decolorization of OMW. However, C. gallica gave the
      highest decolorization and dephenolization rates at 30 % v/v OMW dilution in
      water. Fungal growth in OMW medium was affected by several parameters including
      phenolic compound concentration, nitrogen source, and inoculum size. The optimal
      OMW medium for the removal of phenolics and color was with the OMW concentration
      (in percent)/[(NH4)2SO4]/inoculum ratio of 30:6:3. Under these conditions, 90 and
      85 % of the initial phenolic compounds and color were removed, respectively. High
      pressure liquid chromatography analysis of extracts from treated and untreated
      OMW showed a clear and substantial reduction in phenolic compound concentrations.
      Phytotoxicity, assessed using radish (Raphanus sativus) seeds, indicated an
      increase in germination index of 23-92 % when a 30 % OMW concentration was
      treated with C. gallica in different dilutions (1/2, 1/4, and 1/8).

PMID- 23979848
TI  - Organic and elemental carbon associated to PM10 and PM 2.5 at urban sites of
      northern Greece.
AB  - Organic carbon (OC) and elemental carbon (EC) concentrations, associated to PM10
      and PM2.5 particle fractions, were concurrently determined during the warm and
      the cold months of the year (July-September 2011 and February-April 2012,
      respectively) at two urban sites in the city of Thessaloniki, northern Greece, an
      urban-traffic site (UT) and an urban-background site (UB). Concentrations at the
      UT site (11.3 +/- 5.0 and 8.44 +/- 4.08 14 MUg m(-3) for OC10 and OC2.5 vs. 6.56
      +/- 2.14 and 5.29 +/- 1.54 MUg m(-3) for EC10 and EC2.5) were among the highest
      values reported for urban sites in European cities. Significantly lower
      concentrations were found at the UB site for both carbonaceous species,
      particularly for EC (6.62 +/- 4.59 and 5.72 +/- 4.36 MUg m(-3) for OC10 and OC2.5
      vs. 0.93 +/- 0.61 and 0.69 +/- 0.39 MUg m(-3) for EC10 and EC2.5). Despite that,
      a negative UT-UB increment was frequently evidenced for OC2.5 and PM2.5 in the
      cold months possibly indicative of emissions from residential wood burning at the
      urban-background site. At both sites, cconcentrations of OC fractions were
      significantly higher in the cold months; on the contrary, EC fractions at the UT
      site were prominent in the warm season suggesting some influence from maritime
      emissions in the nearby harbor area. Secondary organic carbon, being estimated
      using the EC tracer method and seasonally minimum OC/EC ratios, was found to be
      an appreciable component of particle mass particularly in the cold season. The
      calculated secondary contributions to OC ranged between 35 and 59 % in the PM10
      fraction, with relatively higher values in the PM2.5 fraction (39-61 %). The
      source origin of carbonaceous species was investigated by means of air parcel
      back trajectories, satellite fire maps, and concentration roses. A local origin
      was mainly concluded for OC and EC with limited possibility for long range
      transport of biomass (agricultural waste) burning aerosol.

PMID- 23979850
TI  - Characterization of the interactions between tetracycline antibiotics and
      microbial extracellular polymeric substances with spectroscopic approaches.
AB  - The antibiotics have attracted global attentions for their impact on aquatic
      ecosystem. The knowledge about the fate of antibiotics encountering extracellular
      polymeric substances (EPS) is, however, limited. In this study, we investigated
      the interacting mechanisms of tetracycline (TC) to EPS extracted from aerobic
      activated sludge. The contributions of the main components of EPS, extracellular
      proteins, and polysaccharides were evaluated using bovine serum albumin and
      alginate sodium, respectively. Fourier transform infrared spectroscopy, X-ray
      photoelectron spectroscopy, and nuclear magnetic resonance indicated that
      hydroxyl, carboxyl, and amino groups were the domain chemical groups involved in
      the interaction between TC and EPS, and the binding of TC onto EPS changed the
      structure of these chemical groups, thus causing shifts in their UV-visible
      absorption spectra. In addition, we found that extracellular proteins, rather
      than polysaccharides, were the major active contents involved in the interaction.
      Three-dimensional excitation-emission matrix fluorescence spectroscopy showed
      that the fluorophores in EPS were clearly quenched by TC and the static quenching
      process was observed, implying the complex formation of TC and EPS. Furthermore,
      thermodynamic analysis indicated that the binding of TC with EPS is spontaneous
      and dominated by electrostatic forces. 

PMID- 23979849
TI  - Bioremediation trial on aged PCB-polluted soils--a bench study in Iceland.
AB  - Polychlorinated biphenyls (PCBs) pose a threat to the environment due to their
      high adsorption capacity to soil organic matter, stability and low reactivity,
      low water solubility, toxicity and ability to bioaccumulate. With Icelandic
      soils, research on contamination issues has been very limited and no data has
      been reported either on PCB degradation potential or rate. The goals of this
      research were to assess the bioavailability of aged PCBs in the soils of the old
      North Atlantic Treaty Organization facility in Keflavik, Iceland and to find the
      best biostimulation method to decrease the pollution. The effectiveness of
      different biostimulation additives (N fertiliser, white clover and pine needles)
      at different temperatures (10 and 30  degrees C) and oxygen levels (aerobic and
      anaerobic) were tested. PCB bioavailability to soil fauna was assessed with
      earthworms (Eisenia foetida). PCBs were bioavailable to earthworms
      (bioaccumulation factor 0.89 and 0.82 for earthworms in 12.5 ppm PCB soil and in
      25 ppm PCB soil, respectively), with less chlorinated congeners showing higher
      bioaccumulation factors than highly chlorinated congeners. Biostimulation with
      pine needles at 10  degrees C under aerobic conditions resulted in nearly 38 %
      degradation of total PCBs after 2 months of incubation. Detection of the aerobic
      PCB degrading bphA gene supports the indigenous capability of the soils to
      aerobically degrade PCBs. Further research on field scale biostimulation trials
      with pine needles in cold environments is recommended in order to optimise the
      method for onsite remediation.

PMID- 23979851
TI  - Enhancing phytoextraction of Cd by combining poplar (clone "I-214") with
      Pseudomonas fluorescens and microbial consortia.
AB  - The plant-microorganism combinations may contribute to the success of
      phytoextraction of heavy metal-polluted soil. The purpose of this study was to
      investigate the effects of cadmium (Cd) soil concentration on selected
      physiological parameters of the poplar clone "I-214" inoculated at root level
      with a strain (BT4) of Pseudomonas fluorescens and a commercial product based on
      microbial consortia (Micosat F Fito(r)). Plants were subjected to Cd treatment of
      40 mg kg(-1) in greenhouse. The effects of plant-microbe interactions, plant
      growth, leaf physiology, and microbial activity were periodically monitored.
      Metal concentration and translocation factors in plant tissues proved enhanced Cd
      uptake in roots of plants inoculated with P. fluorescens and transfer to shoots
      in plants inoculated with Micosat F Fito(r), suggesting a promising strategy for
      using microbes in support of Cd uptake. Plant-microbe integration increased total
      removal of Cd, without interfering with plant growth, while improving the
      photosynthetic capacity. Two major mechanisms of metal phytoextraction inducted
      by microbial inoculation may be suggested: improved Cd accumulation in roots
      inoculated with P. fluorescens, implying phytostabilization prospective and high
      Cd transfer to shoots of inoculated plants, outlining enhanced metal
      translocation.

PMID- 23979852
TI  - Adsorption of fluoranthene in surfactant solution on activated carbon:
      equilibrium, thermodynamic, kinetic studies.
AB  - Adsorption of fluoranthene (FLA) in surfactant solution on activated carbon (AC)
      was investigated. Isotherm, thermodynamic, and kinetic attributes of FLA
      adsorption in the presence of the surfactant on AC were studied. Effects of AC
      dosage, initial concentration of TX100, initial concentration of FLA, and
      addition of fulvic acid on adsorption were studied. The experimental data of both
      TX100 and FLA fitted the Langmuir isotherm model and the pseudo-second-order
      kinetic model well. Positive enthalpy showed that adsorption of FLA on AC was
      endothermic. The efficiency of selective FLA removal generally increased with
      increasing initial surfactant concentration and decreasing fulvic acid
      concentration. The surface chemistry of AC may determine the removal of
      polycyclic aromatic hydrocarbons. The adsorption process may be controlled by the
      hydrophobic interaction between AC and the adsorbate. The microwave irradiation
      of AC may be a feasible method to reduce the cost of AC through its regeneration.

PMID- 23979853
TI  - Tigecycline in febrile neutropenic patients with haematological malignancies: a
      retrospective case documentation in four university hospitals.
AB  - OBJECTIVES: Tigecycline (TGC) is a first-in-class glycylcycline with an expanded
      spectrum of activity. Although TGC has not been prospectively studied in febrile
      neutropenia (FN), we observed that occasionally critically ill neutropenic
      patients unresponsive to other antibiotics were treated with TGC in our
      departments. The aim of our study was to analyse effectiveness and toxicity of
      TGC in FN. METHODS: Data of infectious episodes treated with TGC were
      retrospectively collected. Baseline data of patients, haematological malignancy,
      infection and adverse events were documented. Success was defined as
      defervescence (>=7 days) in the absence of any sign of persistent infection.
      RESULTS: Data of 35 patients with haematological malignancies and FN were
      evaluated. Median duration of neutropenia was 25 days (range 6-69 days). The type
      of infection was pneumonia in 24 patients, four microbiologically documented
      infections, three clinically documented infections and four with fever of unknown
      origin. The TGC was administered after a median of two (range 1-5) prior
      antibiotic regimens. Treatment was successful in 15 (43 %) patients. In patients
      with prolonged neutropenia (>=28 days), response was significantly lower (13 vs.
      79 %; p =0.001). Eight (23 %) patients died during the fever episode. Grade 3-4
      toxicity occurred in five (14 %) patients. CONCLUSION: Our results showed
      promising response rates to TGC and very low toxicity rates compared to the
      generally low response rate of third-line antibiotic therapies, indicating that
      TGC may be a successful alternative for salvage treatment of febrile neutropenia,
      but further study is needed.

PMID- 23979854
TI  - Fulminant hepatitis due to human adenovirus.
AB  - PURPOSE: To describe the demographics, clinical manifestations, treatment and
      outcomes of patients with human adenovirus (HAdV) hepatitis. METHODS: A case of
      fulminant HAdV hepatitis in a patient with chronic lymphocytic leukemia receiving
      rituximab and fludarabine is described. We conducted a comprehensive review of
      the English-language literature through May, 2012 in search of definite cases of
      HAdV hepatitis. RESULTS: Eighty-nine cases were reviewed. Forty-three (48 %) were
      liver transplant recipients, 19 (21 %) were bone marrow transplant recipients, 11
      (12 %) had received chemotherapy, five (6 %) had severe combined
      immunodeficiency, four (4 %) were HIV infected, two had heart transplantation,
      and two were kidney transplant recipients. Ninety percent (46/51) of patients
      presented within 6 months following transplantation. Fever was the most common
      initial symptom. Abdominal CT scan revealed hypodense lesions in eight of nine
      patients. Diagnosis was made by liver biopsy in 43 (48 %), and on autopsy in 46
      (52 %). The HAdV was isolated at other sites in 54 cases. Only 24 of 89 patients
      (27 %) survived: 16 whose immunosuppression was reduced, six with liver re
      transplantation, and two who received cidofovir and intravenous immunoglobulin.
      CONCLUSION: HAdV hepatitis can manifest as a fulminant illness in
      immunocompromised hosts. Definitive diagnosis requires liver biopsy. Early
      consideration of a viral etiology, reduction in immunosuppression, and liver
      transplantation can be potentially life-saving.

PMID- 23979856
TI  - An immunophenotypic and molecular diagnosis of composite hairy cell leukaemia and
      chronic lymphocytic leukaemia.
AB  - Hairy cell leukaemia (HCL) and chronic lymphocytic leukaemia (CLL) are distinct
      clinicopathological B cell chronic lymphoproliferative disorders (B-CLPD). Both
      diseases have characteristic immunophenotypic and molecular features. The co
      existence of two B-CLPD is perhaps more common than previously thought but a
      composite HCL and CLL has been rarely documented. A case is reported in which the
      morphology, integrated with an extensive immunophenotyping panel, and
      incorporation of the recently described HCL-associated BRAF V600E mutation,
      enabled the prompt diagnosis of composite HCL and CLL thus allowing appropriate
      treatment selection. This case serves to highlight the benefit of a
      multidisciplinary approach to the diagnosis of bi-clonal B-CLPD. 

PMID- 23979857
TI  - Low expression of long noncoding RNA GAS6-AS1 predicts a poor prognosis in
      patients with NSCLC.
AB  - Lung cancer is the most frequent cancer in China and all over the world. Recent
      studies have shown that long noncoding RNAs play critical roles in multiple
      biological processes including oncogenesis. In this study, we reported a new
      lncRNA GAS6-AS1 (GAS6 antisense RNA 1), whose expression was downregulated in
      tumor tissues in 50 patients with non-small cell lung cancer (NSCLC) compared
      with those in the adjacent normal tissues (P < 0.001). Furthermore, decreased
      GAS6-AS1 expression was negatively correlated with lymph node metastasis (P =
      0.032) and advanced tumor node metastasis stage (P = 0.003). Univariate and
      multivariate analyses showed that GAS6-AS1 expression served as an independent
      predictor for overall survival (P = 0.036). Also, GAS6-AS1 level was inversely
      correlated with GAS6 (growth-arrest-specific gene6) mRNA level (Pearson's
      correlation -0.620). In conclusion, our study demonstrated that altered lncRNA
      GAS6-AS1 expression might be involved in the development and progression of NSCLC
      by influencing its host gene and promised to be a potential diagnostic target in
      patients with NSCLC.

PMID- 23979858
TI  - Inner ventricular structures and valves of the heart in white rhinoceros
      (Ceratotherium simum).
AB  - In this study, we describe the internal structures of both ventricles and the
      valvular apparatus of the heart of the white rhino. In the right of the heart,
      three papillary muscles were found in septal and marginal walls and m. papillaris
      magnus was the biggest. There was only one m. papillaris parvus in the right
      ventricle. The right atrioventricular valve was tricuspid, and the parietal cusp
      was longest. In the left of the heart, two papillary muscles were found on the
      septal wall and the subauricular was the biggest. The left atrioventricular valve
      was bicuspid and the parietal cusp was longest. There were no nodules in the
      valves of the pulmonary trunk and aorta, and the semilunar valves had many
      fibrous folds and transparent parts. Within the cardiac skeleton there was a
      cartilago cordis which occupied a small part of the right fibrous trigone. While
      the right ventricle included only one septomarginal trabecula, there were many
      trabeculae in the left ventricle. In both ventricles, the endocardium was thin
      and the subendocardial network was visible, also their continuation with the
      septomarginal trabeculae. We also found many trabeculae carneae in the dorsal
      part of the ventricles. 

PMID- 23979859
TI  - Inflammation and atherosclerosis: disease modulating therapies.
AB  - OPINION STATEMENT: Advances in the mechanistic understanding of atheroma
      initiation, repair, progression, and rupture have solidified the pivotal role
      played by the immune system in the pathophysiology of atherosclerotic vascular
      disease. These mechanistic findings have been extended into humans, with a strong
      evidence basis for the independent association between elevated blood markers of
      inflammation and future cardiovascular (CV) events. Investigations with statins
      as well as more conventional anti-inflammatory medications provide indirect
      evidence to support the concept that modifying immune responses can improve CV
      outcomes; however, robust evidence to support the use of anti-inflammatory
      treatment strategies to manage atherosclerotic vascular disease is still lacking.
      Such evidence may emerge from a new wave of clinical trials directly exploring
      the effects of targeted immune modulation on CV risk. These trials will provide
      key additional insights into atherosclerosis and will help determine the fate of
      immune modulation as a new treatment strategy in atherosclerotic vascular
      disease.

PMID- 23979860
TI  - Anti-JCV antibodies detection and JCV DNA levels in PBMC, serum and urine in a
      cohort of Spanish Multiple Sclerosis patients treated with natalizumab.
AB  - One of the most effective multiple sclerosis (MS) treatment is natalizumab.
      Nevertheless, it has been associated with an increased risk of progressive
      multifocal leukoencephalopathy (PML) caused by the JC virus (JCV). Our main
      objective was to assess the utility of testing JCV-DNA, apart from anti-JCV
      antibodies, to determine which natalizumab-treated MS patients has been
      previously in contact with the virus. For this purpose, 138 MS natalizumab/non
      natalizumab treated patients participated in several studies. Cross-sectional
      study (CS): association of several epidemiological variables with anti-JCV
      antibodies and JCV-DNA levels in PBMC/serum/urine. First longitudinal study (A):
      evaluation of JCV-DNA prevalence in urine throughout the treatment. Second
      longitudinal study (B): simultaneous assessment of antibodies and viral DNA
      levels in PBMC/serum/urine at two time points. CS: The seropositivity rate for
      anti-JCV antibodies (62.3 %) and JCV prevalence in urine (59.4 %) were similar;
      although 26 % of our population was positive only using one of the two
      techniques. A: The viral prevalence in urine seemed to increase between the
      baseline visit and the others (Baseline-Visit/V18months, p = 0.006). B: Our rate
      of positive antibody seroconversion was 36 %. Nearly all patients with detectable
      JCV-DNA levels in PBMC excreted the virus intermittently in urine; while our PML
      case, positive in PBMC and serum samples 2 month before the PML, excreted JCV
      permanently. In conclusion, the determination of JCV DNA levels in urine could be
      complementary to anti-JCV antibodies for identifying MS patients who has been
      infected by the JCV. Further research would be necessary to understand the
      different JCV excretion profiles in urine. 

PMID- 23979861
TI  - Relationships key for new CMA president-elect. Interview by Lauren Vogel.

PMID- 23979862
TI  - Uneven accessibility to biomarker test for lung cancer.

PMID- 23979866
TI  - Crowned dens syndrome.

PMID- 23979867
TI  - Ontario newborns now screened for SCID.

PMID- 23979868
TI  - The Cochrane Collaboration 20 years in.

PMID- 23979869
TI  - Rates of readmission and death associated with leaving hospital against medical
      advice: a population-based study.
AB  - BACKGROUND: Leaving hospital against medical advice may have adverse
      consequences. Previous studies have been limited by evaluating specific types of
      patients, small sample sizes and incomplete determination of outcomes. We
      hypothesized that leaving hospital against medical advice would be associated
      with increases in subsequent readmission and death. METHODS: In a population
      based analysis involving all adults admitted to hospital and discharged alive in
      Manitoba from Apr. 1, 1990, to Feb. 28, 2009, we evaluated all-cause 90-day
      mortality and 30-day hospital readmission. We used multivariable regression,
      adjusted for age, sex, socioeconomic status, year of hospital admission, patient
      comorbidities, hospital diagnosis, past frequency of admission to hospital,
      having previously left hospital against medical advice and data clustering
      (patients with multiple admissions). For readmission, we assessed both between
      person and within-person effects of leaving hospital against medical advice.
      RESULTS: Leaving against medical advice occurred in 21 417 of 1 916 104 index
      hospital admissions (1.1%), and was associated with higher adjusted rates of 90
      day mortality (odds ratio [OR] 2.51, 95% confidence interval [CI] 2.18-2.89), and
      30-day hospital readmission (within-person OR 2.10, CI 1.99-2.21; between-person
      OR 3.04, CI 2.79-3.30). In our additional analyses, elevated rates of readmission
      and death associated with leaving against medical advice were manifest within 1
      week and persisted for at least 180 days after discharge. INTERPRETATION: Adults
      who left the hospital against medical advice had higher rates of hospital
      readmission and death. The persistence of these effects suggests that they are
      not solely a result of incomplete treatment of acute illness. Interventions aimed
      at reducing these effects may need to include longitudinal interventions
      extending beyond admission to hospital.

PMID- 23979872
TI  - Retinal implant system delivers limited sight to some blind people.

PMID- 23979870
TI  - Parvovirus infection mimicking systemic lupus erythematosus.

PMID- 23979873
TI  - Bioethicists call for investigation into nutritional experiments on Aboriginal
      people.

PMID- 23979874
TI  - The Cochrane Collaboration celebrates 20 years.

PMID- 23979875
TI  - Preferences for colorectal cancer screening techniques and intention to attend: a
      multi-criteria decision analysis.
AB  - BACKGROUND: Despite the expected health benefits of colorectal cancer screening
      programs, participation rates remain low in countries that have implemented such
      a screening program. The perceived benefits and risks of the colorectal cancer
      screening technique are likely to influence the decision to attend the screening
      program. Besides the diagnostic accuracy and the risks of the screening
      technique, which can affect the health of the participants, additional factors,
      such as the burden of the test, may impact the individuals' decisions to
      participate. To maximise the participation rate of a screening program for a new
      colorectal cancer program in the Netherlands, it is important to know the
      preferences of the screening population for alternative screening techniques.
      OBJECTIVE: The aim of this study was to explore the impact of preferences for
      particular attributes of the screening tests on the intention to attend a
      colorectal cancer screening program. METHODS: We used a web-based questionnaire
      to elicit the preferences of the target population for a selection of colon
      screening techniques. The target population consisted of Dutch men and women aged
      55-75 years. The analytic hierarchy process (AHP), a technique for multi-criteria
      analysis, was used to estimate the colorectal cancer screening preferences.
      Respondents weighted the relevance of five criteria, i.e. the attributes of the
      screening techniques: sensitivity, specificity, safety, inconvenience, and
      frequency of the test. With regard to these criteria, preferences were estimated
      between four alternative screening techniques, namely, immunochemical fecal
      occult blood test (iFOBT), colonoscopy, sigmoidoscopy, and computerized
      tomographic (CT) colonography. A five-point ordinal scale was used to estimate
      the respondents' intention to attend the screening. We conducted a correlation
      analysis on the preferences for the screening techniques and the intention to
      attend. RESULTS: We included 167 respondents who were consistent in their
      judgments of the relevance of the criteria and their preferences for the
      screening techniques. The most preferred screening method for the national
      screening program was CT colonography. Sensitivity (weight = 0.26) and safety
      (weight = 0.26) were the strongest determinants of the overall preferences for
      the screening techniques. However, the screening test with the highest intention
      to attend was iFOBT. Inconvenience (correlation [r] = 0.69), safety (r = 0.58),
      and the frequency of the test (r = 0.58) were most strongly related to intention
      to attend. CONCLUSIONS: The multi-criteria decision analysis revealed the
      attributes of the screening techniques that are most important so as to increase
      intention to participate in a screening program. Even though the respondents may
      recognize the high importance of diagnostic effectiveness in the long term, their
      short-term decision to attend the screening tests may be less driven by this
      consideration. Our analysis suggests that inconvenience, safety, and frequency of
      the test are the strongest technique-related determinants of the respondents'
      intention to participate in colorectal screening programs.

PMID- 23979876
TI  - Private expenditures on brand name prescription drugs after generic entry.
AB  - BACKGROUND: Generic drugs offer a less expensive and therapeutically equivalent
      alternative to brand name drugs. Nevertheless, many Canadian private drug plans
      continue to pay for brand name drugs even after generics become available.
      OBJECTIVE: The objective of this study was to quantify the excess spending
      resulting from this practice. METHODS: We used the IMS Brogan PharmaStat database
      to study private-plan drug spending in Ontario from 2000 to 2009. We focused on
      three widely used drug classes: proton pump inhibitors (PPIs), selective
      serotonin reuptake inhibitors (SSRIs), and angiotensin-converting enzyme (ACE)
      inhibitors. For each specific molecule, we determined the difference between what
      private plans spent on the brand name version and what would have been spent if
      an available generic version of the same molecule had been purchased instead.
      RESULTS: We found that prescriptions paid for by private drug plans were often
      filled with brand name drugs after generics became available. This led to excess
      private spending of more than Can$107.8 million for these three drug classes over
      our study period: Can$54.4 million for PPIs, Can$32.4 million for SSRIs and
      Can$21.0 million for ACE inhibitors. INTERPRETATION: Brand name drugs continue to
      be reimbursed by Canadian private drug plans at higher prices even after less
      expensive generic alternatives are available. By mandating generic substitution,
      substantial cost savings on benefit plans could be achieved.

PMID- 23979877
TI  - Establishment of Caenorhabditis elegans SID-1-dependent DNA delivery system in
      cultured silkworm cells.
AB  - The systemic RNA interference defective-1 (SID-1) can transport double-stranded
      RNA (dsRNA) into cytosol across the cytoplasmic membrane. We report here that
      ectopic expression of Caenorhabditis elegans SID-1 allows BmN4 cells to import
      extracellular plasmid dsDNA into cells via the direct soaking method.
      Interestingly, BmN4-SID1 cells incorporate dsRNA and plasmid DNA simultaneously.
      Furthermore, the ectopic SID-1 allows us to establish a stably transformed cell
      line by the simple soaking method. Our results provide an alternative method for
      silkworm gene function analysis with low cost and low cell toxicity. 

PMID- 23979878
TI  - Genetic diversity of stem cells and their functional impact on the development of
      neural tube defects in Eastern population of India.
AB  - Anencephaly and myelomeningocele are the 2 most common forms of neural tube
      defects (NTDs). During embryogenesis large numbers of extrinsic and intrinsic
      factors are responsible for the closing of the neural tube. "Stem cells" maintain
      the pluripotency during differentiation of 3 germ layers, including the neural
      ectoderm. We examined the role of Oct4, Nanog3, and Sox2 genes in the
      etiopathology of NTDs in an eastern Indian population using PCR-based DNA
      analysis. The highest frequency (16%) of complete loss of the Sox2 gene was found
      in NTDs. The highest frequency (48%) of overexpression (upregulation) was found
      for Nanog3, while 40% was observed for Oct4 and Sox2. The odds ratio for cases
      versus controls was from 0.132 at 95% confidence interval = 0.005-1.298 for
      Nanog3 to 2.316 (0.424-13.812) for Oct4. The highest frequency (77%) of
      overexpression for Nanog3 and Sox2 was observed in encephalocele and anencephalic
      patients, while in the comparison of regional variation, i.e., cephalic to caudal
      regions of NTDs, the highest frequency of downregulation (regression) of Nanog3
      and Sox2 was found in lumbosacral myelomeningocele patients. However, cervical
      myelomeningocele patients had the highest frequency of overexpression in all 3
      genes, suggesting that the mutational spectra of stem cells influence the cells
      of the neural crest in NTDs.

PMID- 23979879
TI  - Adaptability and genotypic stability of Coffea arabica genotypes based on
      REML/BLUP analysis in Rio de Janeiro State, Brazil.
AB  - Biannuality in coffee culture causes temporal variability in plant productivity.
      Consequently, it is essential to evaluate genotypes during various crop years to
      ensure selection of productive and stable genotypes. We evaluated the
      effectiveness of simultaneous selection of coffee genotypes along harvests, based
      on productivity, stability, and adaptability, via mixed models, for indication of
      varieties suitable for Rio de Janeiro State. We evaluated 25 genotypes during 4
      crop seasons (2009-2012), in a randomized block design with 5 replications. The
      ranking of genotypes was obtained on the basis of the adaptability and temporal
      stability methods (harmonic average of genetic values, relative performance of
      genetic values, and harmonic mean of the relative performance of the genetic
      values), obtained via restricted maximum likelihood/best linear unbiased
      procedure analysis. The selection accuracy (0.8717), associated with the high
      magnitude of mean heritability, indicate good reliability and prospects for
      success in the indication of agronomically superior genotypes. There was little
      variation in the ordering of genotypes among the environments, indicating low
      influence of harvests in the performance of the genotypes. Five of the 25
      genotypes were superior and could be recommended for planting in the northwestern
      region of Rio de Janeiro State, due to high predicted productivity and stability.
      We recommend that these methodologies for evaluation of productivity, stability,
      and adaptability be included in the selection criteria for recommendation of
      genotypes for commercial plantings.

PMID- 23979880
TI  - Molecular cytogenetics of nucleolar organizer regions in Phyllomedusa and
      Phasmahyla species (Hylidae, Phyllomedusinae): a cytotaxonomic contribution.
AB  - Chromosome numbers, morphology, and nucleolus organizer region (NOR) locations
      are useful cytological characters for taxonomic and evolutionary studies. In this
      study, we provide the first cytogenetic analysis of Phyllomedusa bahiana and
      Phasmahyla spectabilis, and report new cytogenetic data on variation in NOR
      numbers and positions in Phyllomedusa rohdei and Phyllomedusa nordestina using
      conventional staining, AgNOR-banding, and 45S rDNA fluorescence in situ
      hybridization. All 4 species showed 2n = 26 chromosomes. P. spectabilis and P.
      bahiana had only 1 pair of NOR-carrying chromosomes. P. bahiana showed an NOR
      length polymorphism, and a rare homomorphic self-compatibility for both NOR
      lengths in anurans. Variation in the number of NOR-bearing chromosomes was found
      between the sampled populations of P. nordestina, ranging from 3 to 4. This study
      also clarified previous conflicting results concerning the occurrence of inter-
      and intra-population NOR variation in P. rohdei. The variation, confirmed by 45S
      rDNA fluorescence in situ hybridization analysis, was congruent with results
      obtained from AgNOR-banding in all species.

PMID- 23979881
TI  - Genetic evaluation of Alpine goats using different milk control intervals.
AB  - The objective of this study was to compare the results of genetic evaluations by
      using different milk control intervals to reduce the cost of milk yield controls
      without harming the quality of genetic evaluation of the animals. We analyzed
      test day milk yield data from the Goat Sector of Universidade Federal de Vicosa.
      After editing and checking for errors in the database, there were 20,710 records
      of test day milk yield for the 667 first lactations of Alpine goats, constituting
      the complete file, with 7-day control intervals. Information on specific weeks
      was excluded from the complete file to create files with data on control
      intervals of 15, 21, and 28 days. The RENPED program was used to recode the
      pedigree and data files and correct pedigree errors; the WOMBAT program was used
      for genetic evaluations of the 4 files. The following comparison criteria of
      analysis results were used: logarithm of the function of the restricted maximum
      likelihood, length of the analyses in seconds, Pearson and Spearman correlations,
      and common elimination percentage among the areas below the regression curve of
      the genetic values of the animals. Overall, it is recommended that a 7-day
      interval among milk controls should be used in breeding programs and farms with a
      high technical level. Intervals of 14 and 21 days can achieve satisfactory
      results combined with a lower data collection cost for farms with an average-to
      low technical level, less effective size, and genetic variability that depend on
      external genetic material for genetic improvement.

PMID- 23979882
TI  - Genetic evaluation using multi-trait and random regression models in Simmental
      beef cattle.
AB  - The Brazilian Association of Simmental and Simbrasil Cattle Farmers provided
      29,510 records from 10,659 Simmental beef cattle; these were used to estimate
      (co)variance components and genetic parameters for weights in the growth
      trajectory, based on multi-trait (MTM) and random regression models (RRM). The
      (co)variance components and genetic parameters were estimated by restricted
      maximum likelihood. In the MTM analysis, the likelihood ratio test was used to
      determine the significance of random effects included in the model and to define
      the most appropriate model. All random effects were significant and included in
      the final model. In the RRM analysis, different adjustments of polynomial orders
      were compared for 5 different criteria to choose the best fit model. An RRM of
      third order for the direct additive genetic, direct permanent environmental,
      maternal additive genetic, and maternal permanent environment effects was
      sufficient to model variance structures in the growth trajectory of the animals.
      The (co)variance components were generally similar in MTM and RRM. Direct
      heritabilities of MTM were slightly lower than RRM and varied from 0.04 to 0.42
      and 0.16 to 0.45, respectively. Additive direct correlations were mostly positive
      and of high magnitude, being highest at closest ages. Considering the results and
      that pre-adjustment of the weights to standard ages is not required, RRM is
      recommended for genetic evaluation of Simmental beef cattle in Brazil.

PMID- 23979883
TI  - The GSTP1 A1578G polymorphism and the risk of childhood acute lymphoblastic
      leukemia: results from an updated meta-analysis.
AB  - Studies investigating the association between the glutathione S-transferase P1
      (GSTP1) A1578G polymorphism and the risk of childhood acute lymphoblastic
      leukemia (ALL) report conflicting results. The aim of this study was to
      quantitatively summarize the evidence for such a relationship. Two investigators
      independently searched the Medline, Embase, China National Knowledge
      Infrastructure, and Wangfang databases for studies of the polymorphism and ALL.
      Summary odds ratios (ORs) and 95% confidence intervals (CIs) for the GSTP1
      polymorphism and childhood ALL were calculated in a fixed-effect model. Pooled
      ORs were calculated for a co-dominant model (GG vs AA, AG vs AA), a dominant
      model (GG + AG vs AA), and a recessive model (GG vs AA + AG). Analyses were also
      performed in subgroups stratified by race, study design, genotyping methods, and
      study sample size. This meta-analysis included 8 case-control studies with 1384
      childhood ALL cases and 1755 controls. Overall, the variant genotypes (GG and AG)
      of A1578G were not associated with childhood ALL risk, when compared with the
      wild-type homozygote AA genotype (GG vs AA, OR = 1.09, 95%CI = 0.84-1.43; AG vs
      AA, OR = 1.05, 95%CI = 0.91-1.23). Similarly, no associations were found in the
      dominant and recessive models (dominant model, OR = 1.06, 95%CI = 0.92-1.23;
      recessive model, OR = 1.09, 95%CI = 0.84-1.43). Stratified analyses did not
      detect significant association in any subgroup. No heterogeneity or publication
      bias was observed in the present study. This updated meta-analysis indicates that
      the GSTP1 A1578G polymorphism is not associated with the risk of childhood ALL.
      In the future, additional studies in Asian and African-American patients should
      be performed to re-evaluate the association in these populations.

PMID- 23979884
TI  - Optimization of virus-induced gene silencing in pepper (Capsicum annuum L.).
AB  - Virus-induced gene silencing is currently a powerful tool for the study of gene
      function in plants. Here, we optimized the protocol for virus-induced gene
      silencing, and investigated factors that affect the efficiency of tobacco rattle
      virus-induced gene silencing in pepper plants. Consequently, an optimal protocol
      was obtained by the syringe-infiltration method in the leaves of pepper plants.
      The protocol involves 2-leaf stage plants, preparing the Agrobacterium inoculum
      at a final OD600 of 1.0 and then growing the inoculated plants at 22 degrees C.
      Using this protocol, we achieved high efficiency in silencing CaPDS in different
      cultivars of pepper plants. We further used the CaPOD gene to illustrate the
      general reliability of this optimized protocol. Viral symptoms were observed on
      the leaves of inoculated plants of the Early Calwonder cultivar 25 days post
      inoculation, indicating that this protocol can also be used to silence other
      genes in pepper plants. Real-time polymerase chain reaction analyses revealed
      that the expression levels of CaPDS and CaPOD were dramatically reduced in
      inoculated leaves compared to control plants. These results demonstrate that the
      optimized protocol can be applied to functional genomic studies in pepper to
      investigate genes involved in a wide range of biological processes.

PMID- 23979885
TI  - Analysis of differential gene expression during floral bud abortion in radish
      (Raphanus sativus L.).
AB  - Radish floral bud abortion (FBA) is an adverse biological phenomenon that occurs
      during reproduction. Although FBA occurs frequently, its mechanism remains
      unknown. To elucidate the molecular mechanism underlying FBA, we detected gene
      expression differences between aborted and normal buds of radish using cDNA
      amplified fragment length polymorphism (AFLP) and real-time polymerase chain
      reaction (real-time PCR). A total of 221 differentially expressed transcript
      derived fragments (TDFs) were detected by 256 cDNA-AFLP primer combinations, of
      which 114 were upregulated and 107 were downregulated in the aborted buds. A
      total of 54 TDFs were cloned and sequenced. A BLAST search revealed that all TDFs
      have homologous sequences and 29 of these corresponded to known genes, whose
      functions were mainly related to metabolism, stimulus response, transcriptional
      regulation, and transportation. Expressions of 6 TDFs with different functions
      were further analyzed by real-time PCR yielding expression profiling results
      consistent with the cDNA-AFLP analysis. Our results indicated that radish FBA is
      related to abnormalities in various physiological and biochemical plant
      processes.

PMID- 23979886
TI  - Genotoxic evaluation of the antimalarial drugs artemisinin and artesunate in
      human HepG2 cells and effects on CASP3 and SOD1 gene expressions.
AB  - The malaria treatment recommended by the World Health Organization involves
      medicines derived from artemisinin, an active compound extracted from the plant
      Artemisia annua, and some of its derivatives, such as artesunate. Considering the
      lack of data regarding the genotoxic effects of these compounds in human cells,
      the objective of this study was to evaluate the cytotoxicity and genotoxicity,
      and expressions of the CASP3 and SOD1 genes in a cultured human hepatocellular
      liver carcinoma cell line (HepG2 cells) treated with artemisinin and artesunate.
      We tested concentrations of 2.5, 5, 7.5, 10, and 20 MUg/mL of both substances
      with a resazurin cytotoxicity assay, and the concentrations used in the
      genotoxicity experiments (2.5, 5, and 10 MUg/mL) and gene expression analysis (5
      MUg/mL) were determined. The results of the comet assay in cells treated with
      artemisinin and artesunate showed a significant dose-dependent increase (P <
      0.001) in the number of cells with DNA damage at all concentrations tested.
      However, the gene expression analysis revealed no significant change in
      expression of CASP3 or SOD1. Our data showed that although artemisinin and
      artesunate exhibited genotoxic effects in cultured HepG2 cells, they did not
      significantly alter expression of the CASP3 and SOD1 genes at the doses tested.

PMID- 23979888
TI  - TLR4 gene expression in pig populations and its association with resistance to
      Escherichia coli F18.
AB  - TLR4 is the main recognition receptor of bacterial lipopolysaccharides, which
      play an important role in innate and adaptive immunity. We used real-time PCR to
      analyze the tissue expression profile and differential expression of TLR4 in 4
      pig populations (Escherichia coli F18-resistant Sutai, E. coli F18-sensitive
      Sutai, Large White, Meishan), in order to determine the role that the TLR4 gene
      plays in resistance to E. coli F18. We found that TLR4 expressed consistently in
      the 4 populations, with relatively high levels in immune tissues and the highest
      level in the lung. Generally, the expression of TLR4 in E. coli F18-sensitive
      individuals was the highest, followed by that in E. coli F18-resistant, Large
      White and Meishan. In the spleen, lung, kidney, lymph nodes, and thymus gland,
      TLR4 expression is significantly higher in the E. coli F18-sensitive than in the
      other 3 populations; there were no significant differences among E. coli F18
      resistant Sutai, Large White, and Meishan. In addition, Gene Ontology and pathway
      analysis showed that TLR4 takes part in the inflammatory response. We found that
      porcine TLR4 has consistent tissue specificity in each breed, and downregulation
      of expression of the TLR4 gene is related to resistance to E. coli F18 in weaning
      piglets.

PMID- 23979887
TI  - 3p partial trisomy and 13q partial monosomy with congenital malformations and
      psychomotor developmental delay.
AB  - We examined a girl presenting neuropsychomotor developmental delay and multiple
      malformations including antenatal and postnatal growth retardation, congenital
      heart defect, and facial dysmorphisms. Cytogenetic analysis was performed on
      peripheral blood lymphocytes with the GTG-banding technique, which revealed an
      unbalanced translocation: 46,XX,der(13)(13pter->13q34::3p24->3pter)pat. Karyotype
      analysis of the father demonstrated a balanced translocation,
      46,XY,t(3;13)(p24;q34), indicating the inheritance of the derivative chromosome
      13. The mother karyotype was normal. We suggest that most of the structural
      malformations seen in this patient are due to the 3p trisomy, while the
      neuropsychomotor alterations are a consequence of both chromosome aberrations.

PMID- 23979889
TI  - Development and characterization of microsatellite loci in a threatened marine
      fish, Cheilinus undulatus (humphead wrasse).
AB  - Cheilinus undulatus (humphead wrasse) is a marine fish distributed widely
      throughout the tropical Indo-Pacific. It has been listed as vulnerable in the
      IUCN Red Data Book and in CITES Appendix II four times. Fifteen microsatellite
      loci were isolated and characterized for this species. The number of alleles
      ranged from 3 to 15 per locus, and the observed and expected heterozygosity
      ranged between 0.0323-0.7742 and 0.2597-0.8773, respectively. The polymorphism
      information content ranged from 0.2353-0.8520. Four microsatellite loci deviated
      significantly from Hardy-Weinberg expectations. No significant linkage
      disequilibrium was found among any of the loci. These microsatellite loci will be
      useful for future investigations of genetic variation in the wrasse population.

PMID- 23979891
TI  - Variation of the OsGI intron and its phenotypic associations in Oryza rufipogon
      Griff. and Oryza sativa L.
AB  - We analyzed intron 9 of the OsGI gene in Oryza rufipogon and Oryza sativa in
      order to investigate evolutionary relationships in rice and the relationship
      between intron variation and phenotype. OsGI-9 was cloned in 38 O. rufipogon
      populations and in 139 O. sativa cultivars and the phylogeny was reconstructed.
      Seed cold tolerance and dormancy were quantified in O. sativa. Three OsGI-9 band
      types occurred in O. rufipogon: S-type (1.2 kb), F-type (0.9 kb), and FS-type
      (1.2 and 0.9 kb), whereas only the S-type and F-type occurred in O. sativa. The S
      type contains two 255-bp repeats, the F-type contains one 255-bp repeat, and the
      FS-type contains both. All individuals could be divided into 5 groups in the
      organism's phylogenetic network: S-type O. rufipogon, F-type O. rufipogon, FS
      type O. rufipogon, S-type O. sativa, and F-type O. sativa. F-type O. sativa are
      most closely related to F-type O. rufipogon and S-type O. sativa are most closely
      related to S-type O. rufipogon. Statistical analysis indicated that OsGI-9 type
      is significantly correlated with phenotype; most S-type O. sativa have strong
      seed dormancy and cold tolerance, and most F-type O. sativa have no seed dormancy
      and poor cold tolerance.

PMID- 23979890
TI  - Survey of simple sequence repeats in woodland strawberry (Fragaria vesca).
AB  - The use of simple sequence repeats (SSRs), or microsatellites, as genetic markers
      has become popular due to their abundance and variation in length among
      individuals. In this study, we investigated linkage groups (LGs) in the woodland
      strawberry (Fragaria vesca) and demonstrated variation in the abundances,
      densities, and relative densities of mononucleotide, dinucleotide, and
      trinucleotide repeats. Mononucleotide, dinucleotide, and trinucleotide repeats
      were more common than longer repeats in all LGs examined. Perfect SSRs were the
      predominant SSR type found and their abundance was extremely stable among LGs and
      chloroplasts. Abundances of mononucleotide, dinucleotide, and trinucleotide
      repeats were positively correlated with LG size, whereas those of tetranucleotide
      and hexanucleotide SSRs were not. Generally, in each LG, the abundance, relative
      abundance, relative density, and the proportion of each unique SSR all declined
      rapidly as the repeated unit increased. Furthermore, the lengths and frequencies
      of SSRs varied among different LGs.

PMID- 23979892
TI  - Development of microsatellite markers for Mytilus coruscus (Mytilidae), an
      economically important mussel in the East China Sea.
AB  - Twelve new polymorphic microsatellite loci were developed for the hard-shelled
      mussel, Mytilus coruscus. In 32 individuals from a wild population of coastal
      Zhoushan, Zhejiang Province, China, the number of alleles at these loci varied
      from 3 to 15, with a mean of 5.667. The mean observed and expected
      heterozygosities were 0.6927 and 0.6591, respectively. Among these polymorphic
      microsatellite loci, three (MC42, MC129, and MC180) significantly deviated from
      Hardy-Weinberg equilibrium after sequential Bonferroni's correction. All other
      microsatellite loci were in linkage equilibrium. These microsatellite loci will
      be useful for detecting genetic differences and for planning aquaculture
      management of M. coruscus.

PMID- 23979893
TI  - Inheritance of cytosine methylation patterns in purebred versus hybrid chicken
      lines.
AB  - We used methylation-sensitive amplified polymorphism to examine DNA methylation
      levels and CCGG patterns in parents and offsprings of 3 groups of adult chickens,
      purebred White Leghorn (AA), White Plymouth Rock (EE), and crossbred individuals
      (EA) using 10 primer combinations. We found that about 66% of the cytosines at
      CCGG sites were not methylated. Fully methylated sites were less frequent than
      hemi-methylated sites in the chicken genome; these frequencies were different
      from those of plants. We observed that the probability that the offspring would
      inherit the methylation pattern for any given site from the parents was 88%;
      consequently, unexpected methylation patterns in offspring occurred at a rate of
      about 12%. The methylation degree in offspring was lower than in parents, and
      there were more sites with altered methylation patterns in EA crossbreds compared
      with AA and EE purebreds. Seven differentially methylated fragments between
      parental lines and their offspring were isolated, sequenced, and characterized, 4
      of which were located in the coding regions. We conclude that most of the
      methylation status is transferred from parents to offspring in chickens, and that
      there are differences in the inheritance of methylation status in purebred versus
      crossbred offspring. We also concluded that methylation-sensitive amplified
      polymorphism is highly efficient for large-scale detection of cytosine
      methylation in the chicken genome. 

PMID- 23979894
TI  - Cloning and characterization of thioredoxin h in the three-pistil line of common
      wheat.
AB  - Thioredoxin h (Trxh) is a ubiquitous protein that reduces disulfides in target
      proteins, and is itself reduced by NADPH-thioredoxin reductase. In the current
      study, the complementary DNA sequence and the genomic sequence of the three
      pistil (TP) line of common wheat (Triticum aestivum L.) were obtained from spikes
      through reverse transcription-polymerase chain reaction (RT-PCR) and touchdown
      PCR. Sequence alignment of amino acids of TPTrxh then allowed for predictions of
      its physicochemical properties, secondary structures, tertiary structures, and
      functional domains. Furthermore, the TPTrxh gene was overexpressed in Escherichia
      coli and its activity was demonstrated using a dithiothreitol-dependent insulin
      assay. The expression patterns of TPTrxh were analyzed through real-time RT-PCR
      in different tissues and across different developmental stages of young spikes.
      The complementary DNA of TPTrxh was found to be 411 bp in length, encoding 118
      amino acids. Its genomic sequence was determined to be 2632 bp, possessing 3
      exons and 2 introns. Functional domain analysis indicated that TPTrxh contained a
      WCGPC motif located at the end of the second beta-fold and on the initial side of
      the second alpha-helix. The TPTrxh protein reduces intramolecular and
      intermolecular disulfide bridges in target proteins. Young spikes contain higher
      levels of TPTrxh transcripts than do stems and leaves. The transcript levels in
      the young spikes (2-5 mm in length) of the Chinese Spring TP line increased 2.84
      fold relative to those of young spikes (2-5 mm in length) of the Chinese Spring
      line. These data provide a basis for future research into the function of Trxh,
      and offer further insight into the molecular mechanism of the TP mutation in
      wheat.

PMID- 23979895
TI  - Single nucleotide polymorphisms in immunity-related genes and their association
      with mastitis in Chilean dairy cattle.
AB  - Mastitis remains a major cattle disease with great global economic implications.
      Various approaches are currently employed in attempts to improve understanding of
      mastitis resistance and develop phenotypic markers for use in breeding programs
      (e.g., somatic cell score), including QTL discovery, wide-genome association
      studies, and identification of candidate genes related to immune function. This
      study evaluated three single nucleotide polymorphisms contained in Toll-like
      receptor 4 (TLR4) and lactoferrin (LF) genes associated with mastitis traits:
      TLR4 P-226, TLR4 2021, and LF P-28. Genotyping was performed by restriction
      fragment length polymorphism-polymerase chain reaction (PCR) and high-resolution
      melting quantitative PCR from genomic DNA of four dairy cattle breeds (Holstein,
      Jersey, Montbeliarde, and Overo Colorado) previously classified as healthy, with
      clinical or with subclinical mastitis. The high-resolution melting quantitative
      PCR allowed genotyping of each locus and resulted in allele frequencies
      indicating that all loci were in Hardy-Weinberg equilibrium. The TT genotype of
      TLR4 2021 was significantly associated with the healthy condition, but no
      associations with somatic cell score were evident. Further studies are therefore
      necessary in order to confirm the results of this investigation.

PMID- 23979896
TI  - Assessment of toxic, genotoxic, antigenotoxic, and recombinogenic activities of
      Hymenaea courbaril (Fabaceae) in Drosophila melanogaster and mice.
AB  - Hymenaea courbaril L., popularly known as jatoba, is a plant species that grows
      in the forests of South America. The species has been used for culinary purposes
      and in folk medicine to treat arthritis and inflammations. Due to the increasing
      use of this plant globally, the present study aimed to evaluate the toxic,
      genotoxic, recombinogenic, and antigenotoxic effects of H. courbaril sap (Hycs)
      using the mouse bone marrow micronucleus test and the somatic mutation and
      recombination test (SMART) in Drosophila melanogaster. To evaluate the aneugenic
      and clastogenic activities revealed by the micronucleus test, the animals were
      treated with 3 doses of Hycs (5, 10, and 15 mL/kg body weight). To evaluate the
      antianeugenic and anticlastogenic activities, the animals were simultaneously
      treated with Hycs and mitomycin C (4 mg/kg body weight). To assess the mutagenic
      and recombinogenic activities using SMART, 3-day-old larvae derived from standard
      and high bioactivation crosses were treated with 3 doses of Hycs (3.0, 1.5, and
      0.3 mL) for approximately 48 h. To evaluate antimutagenic and antirecombinogenic
      activities, larvae derived from both crosses were co-treated with 3 doses of Hycs
      (3.0, 1.5, and 0.3 mL) and doxorubicin (0.125 mg/ mL). The mouse bone marrow
      micronucleus test revealed that Hycs exhibited no cytotoxic, clastogenic and/or
      aneugenic effects, but did show anticytotoxic, anticlastogenic and/or
      antianeugenic activities. The SMART revealed no mutagenic or recombinogenic
      effects, but antimutagenic and antirecombinogenic activities were observed in
      somatic cells of D. melanogaster from both crosses.

PMID- 23979897
TI  - Association of novel single nucleotide polymorphisms of the CXCR1 gene with the
      milk performance traits of Chinese native cattle.
AB  - Mastitis is an economically devastating disease affecting the dairy industry.
      Dairy cows with mastitis give reduced milk yield and produce milk that is unfit
      for consumption. The chemokine receptor CXCR1 is an excellent prospective genetic
      marker for mastitis resistance in cattle because it regulates neutrophil
      migration, killing, and survival during infection. We detected 4 single
      nucleotide polymorphisms (SNPs) of the CXCR1 gene in Chinese native cattle and
      analyzed their associations with milk traits. Screening for genetic variations in
      CXCR1 among 648 Chinese Holstein, Luxi Yellow, and Bohai Black cattle by created
      restriction site polymerase chain reaction (PCR), nested PCR, and DNA sequencing
      revealed 4 new SNPs with allelic frequencies ranging from 0.676 to 0.821, 0.706
      to 0.803, 0.647 to 0.824, and 0.558 to 0.581. All four CXCR1 gene SNPs were
      located in exon II. Two SNPs, c.337A>G and c.365C>T, were nonsynonymous mutations
      [ATC (Ile) > GTC (Val) and GCC (Ala) > GTC (Val)], whereas two, c.291C>T and
      c.333C>T, were synonymous mutations [TTC (Gly) > TTT (Gly) and GGC (Phe) > GGT
      (Phe)]. Statistical analyses revealed the significant association of c.337A>G and
      c.365C>T with the somatic cell score, which suggests the possible role of these
      SNPs in the host response against mastitis. Our data suggest that combined
      genotypes CCAC/CCGC, CCAC/CTAT, and CCAT/CTAT (lowest somatic cell scores);
      CTAC/CTAT (highest protein rate); CCAC/CTGC (highest fat rate); and CCAT/CTAT
      (highest 305-day milk yield) can be used as possible candidates for marker
      assisted selection in dairy cattle breeding programs.

PMID- 23979898
TI  - Molecular phylogeny of Threskiornithidae (Aves: Pelecaniformes) based on nuclear
      and mitochondrial DNA.
AB  - The family Threskiornithidae includes 13 genera and 32 species, and it is
      traditionally divided into 2 subfamilies: Plataleinae and Threskiornithinae. We
      present a phylogenetic reconstruction to test the monophyly of currently accepted
      subfamilies, including 15 species from both subfamilies and 10 genera of family
      Threskiornithidae. Phylogenetic trees were inferred on the basis of the
      mitochondrial 16S rRNA gene and the nuclear intron 7 of beta-fibrinogen.
      Threskiornithidae was recovered as a monophyletic group. Plataleinae formed a
      monophyletic group, but nested within Threskiornithinae, which was thus
      paraphyletic. Two major phylogenetic groups were identified: the 'endemic New
      World clade', including genera endemic to the American continent, and the
      'widespread clade', comprising the remaining species. These phylogenetic groups
      diverged about 39-42 million years ago, i.e., before the separation of South
      America and Antarctica. Our results agree with an initial vicariance due to
      Gondwana break-up and subsequent colonization of species from the Old World to
      the New World.

PMID- 23979899
TI  - Characterization of new microsatellite markers of Siganus fuscescens (Siganidae).
AB  - Siganus fuscescens, which is a small commercially important marine fish, is
      wildly distributed in shallow waters throughout the tropical and subtropical Indo
      Pacific and Eastern Mediterranean regions. It is part of a group known as
      rabbitfish. Fifteen new polymorphic microsatellite markers for S. fuscescens were
      identified, and 32 wild individuals were used to evaluate the degree of
      polymorphism of these markers. The number of alleles per locus ranged from 2 to
      12, and the polymorphism information content ranged from 0.210 to 0.849. The
      observed and expected heterozygosities were 0.142-0.808 and 0.225-0.853,
      respectively. Although significant deviations from Hardy-Weinberg equilibrium
      were detected at 2 loci (Sf1-37-2 and Sf1-47), no significant deviations were
      detected at the other 13 loci. These microsatellite markers will provide a useful
      tool for studies on genetic diversity and differentiation of S. fuscescens.

PMID- 23979900
TI  - Association analysis of vitamin D receptor gene polymorphisms and bone mineral
      density in postmenopausal Mexican-Mestizo women.
AB  - We investigated associations between vitamin D receptor (VDR) gene polymorphisms,
      FokI T>C (rs2228570), BsmI G>A (rs1544410), ApaI G>T (rs7975232), and TaqI T>C
      (rs731236), with bone mineral density (BMD) in postmenopausal Mexican-Mestizo
      women. Three hundred and twenty postmenopausal women participated, who were
      classified according to World Health Organization criteria as non-osteoporotic
      (Non-OP; N = 88), osteopenic (Opn; N = 144), and osteoporotic (OP; N = 88). BMD
      measurements at the lumbar (L1-L4) spine and at the left and right femoral neck
      were obtained by dual-energy X-ray absorptiometry. Single nucleotide
      polymorphisms (SNPs) were genotyped using real-time polymerase chain reaction and
      TaqMan probes. Genotype and allelic frequencies of the 4 VDR SNPs were similar
      among the 3 groups. Polymorphic allele frequencies were as follows: FokI (C)
      0.53, 0.49, 0.56; BsmI (A) 0.26, 0.22, 0.23; ApaI (T) 0.43, 0.39, 0.44; TaqI (C)
      0.27, 0.22, 0.23 for the Non-OP, Opn, and OP groups, respectively. Although no
      associations were found between the SNPs and BMD, based on the putative function
      of the FokI SNP, we constructed, for the first time, the haplotype with the 4 VDR
      SNPs, and found that the CGGT haplotype differed between the Non- OP and OP
      groups (21.8 vs 31.8%, P < 0.05). The risk analysis for this haplotype was nearly
      significant under the dominant model (OR = 1.783, 95%CI = 0.98-3.25, P = 0.058).
      This result suggests a possible susceptibility effect of the C allele of the FokI
      SNP for the development of osteoporosis in postmenopausal Mexican-Mestizo women.

PMID- 23979901
TI  - GSTM1 and GSTT1 polymorphisms in endometriosis in women from Goias, Brazil.
AB  - Endometriosis is a gynecologic pathology with a high prevalence and unknown
      etiology. Therefore, an increasing number of studies has been undertaken to
      search for associations between endometriosis and alterations or polymorphisms in
      candidate genes, including glutathione S-transferase mu 1 (GSTM1) and glutathione
      S-transferase theta 1 (GSTT1). We analyzed the frequency of present/absent
      polymorphisms of GSTM1 and GSTT1 in 50 women diagnosed with endometriosis and in
      a control group of 46 women without complaints related to this pathology. The
      association of these polymorphisms with p53 gene codon 72 was also evaluated
      within each group, and a higher frequency of absence of GSTM1 (61%) and GSTT1
      (45%) genes in the group of women studied, women with endometriosis and control
      group was found. The contributions of GSTM1 and GSTT1 polymorphisms to the
      proliferation of endometriosis were not statistically significant, but the
      analysis of pathology and the association of GSTM1 and GSTT1 gene polymorphisms
      with p53 codon 72 revealed statistical significance.

PMID- 23979902
TI  - Multiple abnormalities due to a nonsense mutation in the Alx4 gene.
AB  - Patterning of the limb anterior-posterior axes depends on several signals that
      derive from the three signaling centers of the limb bud. These signals interact
      to constitute a complex and ordered network that critically contributes to the
      development of limb buds. Preaxial polydactyly in mouse is predominantly caused
      by ectopic expression of the zone of polarizing activity or Sonic hedgehog in the
      anterior region of the limb bud. In this study, we describe an N-ethyl-N
      nitrosourea-induced polydactylous mouse (Alx4m1Yzcm) with an extra digit on the
      anterior aspect of one or two hinddigits. The mutation was mapped to chromosome
      2, between markers D2Mit45 and D2Mit184. The Alx4 gene was identified as a
      potential candidate gene in this location. Sequence analysis of the Alx4 gene for
      polydactylous heterozygotes revealed an A/T transversion mutation that resulted
      in substitution of a lysine codon with a stop (nonsense) codon at position 145.
      Alx4m1Yzcm homozygous mice exhibited multiple abnormalities, including extensive
      preaxial polydactyly of all four limbs (up to seven digits) and the formation of
      omphalocele.

PMID- 23979903
TI  - Novel tetranucleotide microsatellite markers for Chinese beard eel (Cirrhimuraena
      chinensis Kaup).
AB  - In this study, we characterized 12 novel polymorphic microsatellite loci for
      Chinese beard eel (Cirrhimuraena chinensis Kaup) from a tetranucleotide
      microsatellite-enriched library. Loci screened on a sample of 37 individuals from
      Xiamen wild stocks revealed 8 to 24 alleles per locus, with a mean of 13.83 over
      all loci. Observed and expected heterozygosities ranged from 0.270 to 0.944 and
      0.439 to 0.942, respectively. These efficient genetic markers thus provide useful
      tools in the study of the population genetics and phylogeography of Chinese beard
      eel.

PMID- 23979904
TI  - Microanatomy of the placenta of Lycopodium obscurum: novel design in an
      underground embryo.
AB  - BACKGROUND AND AIMS: Long-lived underground populations of mycoheterotrophic
      gametophytes and attached sporophytes at various developmental stages occur in
      lycophytes. Young underground sporophytes obtain carbon solely from the
      gametophyte and establish nutritional independence only after reaching the soil
      surface, which may take several years. This prolonged period of matrotrophy
      exceeds that of bryophytes. The foot is massive and provides the lifeline for
      sporophyte establishment, yet the fine structure of the placental region is
      unexplored in lycophytes with underground gametophytes. METHODS: Gametophytes
      with attached embryos/young sporophytes of Lycopodium obscurum were collected in
      nature, processed and examined by light and transmission electron microscopy. KEY
      RESULTS: Three ultrastructurally distinct regions were identified within a single
      foot of a sporophyte emerging from the soil. Young foot regions actively divide,
      and have direct contact with and show little differentiation from gametophyte
      cells. In unlobed foot areas, cells in both generations exhibit polarity in
      content and indicate unidirectional transport of carbon reserves into the foot
      toward the developing shoot and root. The foot has inconspicuous wall ingrowths.
      Highly lobed foot regions contain peripheral transfer cells with prominent wall
      ingrowths that absorb nutrients from degenerating gametophyte cells. CONCLUSIONS:
      Variability within a single placenta is consistent with an invasive and long
      lived foot. The late appearance of wall ingrowths in transfer cells reflects this
      dynamic ever-growing embryo. Placental features in lycophytes are related to the
      unique reorientation of all embryonic regions during development. Small placentas
      with wall ingrowths in both generations characterize ephemeral embryos in green
      gametophytes, while short-lived and repositioning embryos of heterosporous taxa
      are devoid of transfer cells. Transfer cell evolution across embryophytes is
      riddled with homoplasy and reflects diverse patterns of embryology. Scrutiny of
      placental evolution must include consideration of nutritional status and life
      history strategies of the gametophyte and young sporophyte.

PMID- 23979905
TI  - Treatment Options for Medulloblastoma and CNS Primitive Neuroectodermal Tumor
      (PNET).
AB  - OPINION STATEMENT: Medulloblastoma and central nervous system (CNS) primitive
      neuroectodermal tumor (PNET) are primary pediatric brain tumors that require
      multidisciplinary therapies. Although often treated similarly in clinical trials,
      they are biologically different diseases. Even within medulloblastomas and CNS
      PNETs, there are molecularly distinct subgroups with differing presentations and
      prognoses. Overall, prognosis is better for medulloblastomas. Specific treatments
      for these types of cancer are continuously evolving to maximize survival and
      minimize long-term sequelae of treatment. Patients should be treated on a
      clinical trial, if eligible, as they may gain benefit with minimal risk over
      current standard of care. The amount of residual disease after surgery better
      correlates with survival for medulloblastomas than for CNS PNETs. Maximal
      surgical resection of tumor should be done, only if additional permanent,
      neurologic deficits can be spared. Patients should have a staging work-up to
      assess the extent of disease. This includes postoperative magnetic resonance
      imaging (MRI) of the brain, MRI of the entire spine and lumbar cerebrospinal
      fluid (CSF) sampling for cytological examination, if deemed safe. Radiation
      therapy to the entire CNS axis is required, with a greater dose (boost) given to
      the region of the primary site or any bulky residual disease for older children.
      Adjuvant chemotherapy must be given even if no evidence of disease after
      radiation therapy exists, as the risk of relapse is substantial after radiation
      alone. Subsets of younger children with medulloblastoma, arbitrarily defined as
      those younger than 3 years of age in some studies and 4 or even 5 years in other
      studies, can be effectively treated with chemotherapy alone. Recent genomic
      studies have revealed further subtypes of disease than previously recognized.
      Clinical trials to exploit these biologic differences are required to assess
      potential efficacy of targeted agents. The treatment of medulloblastoma and CNS
      PNET can cause significant impairment in neurologic function. Evaluations by
      physical therapy, occupational therapy, speech therapy and neurocognitive
      assessments should be obtained, as needed. After therapy is completed, survivors
      need follow-up of endocrine function, surveillance scans and psychosocial
      support.

PMID- 23979906
TI  - Enhanced regeneration of rabbit mandibular defects through a combined treatment
      of electrical stimulation and rhBMP-2 application.
AB  - We evaluated the new bone regeneration of a rabbit mandibular defect using hBMSCs
      under electrical stimulation combined with rhBMP-2 in this study. An inner
      scaffold prepared by setting a collagen sponge with hBMSCs and hydrogel was
      placed into a polycaprolactone (PCL) outer box, and an electrical stimulation
      device was installed between the inner scaffold and the outer box. There were
      three experimental groups depending on electrical stimulation and application of
      rhBMP-2. The experimental group was divided into the following three groups.
      Group 1, in which rhBMP-2 (5 MUg/defect) was added to hydrogel and electrical
      stimulation was not applied; Group 2, in which rhBMP-2 (5 MUg/defect) was added
      as in Group 1 and electrical stimulation was applied; and Group 3, in which
      electrical stimulation was applied and rhBMP-2 (5 MUg/defect) was injected
      directly into defect site. The delivered electrical stimulation was charge
      balanced bi-phasic electric current pulses, and electrical stimulation was
      conducted for 7 days. The stimulation parameters of the bi-phasic electrical
      current set at an amplitude of 20 MUA, a duration of 100 MUs and a frequency of
      100 Hz. Four weeks after surgery, new bone formation in each group was evaluated
      using radiography, histology, and micro-computed tomography (MUCT). Groups 2 and
      3 exhibited a significant increase in new bone formation compared to Group 1,
      while Group 3 showed the highest level of new bone regeneration. In a comparison
      between two groups, Group 2 showed a higher bone volume (BV) by 260 % (p < 0.01)
      compared with Group 1, and Group 3 showed a higher BV by 442 % (p < 0.01)
      compared with Group 1. The trend of the bone surface density (ratio of new bone
      to the real defect volume, BS/TV), trabecular number, and connectivity was
      identical to that of the BV. The total bone mineral density (BMD) of Groups 2 and
      3 showed values higher by the ratios of 103 % (p < 0.01) and 107.5 % (p < 0.01)
      compared with Group 1, respectively. Part BMD for Groups 2 and 3 showed higher
      values by the ratios of 104.9 % (p < 0.01) and 122.4 % (p < 0.01) compared with
      Group 1, respectively. These results suggest that the combined treatment of
      electrical stimulation, hBMSCs, a collagen sponge, hydrogel, and rhBMP-2 was
      effective for bone regeneration of large-size mandibular defects. The application
      of rhBMP-2 with an injection following electrical stimulation demonstrated better
      efficiency as regards bone regeneration. 

PMID- 23979907
TI  - Successful penetration and bougie dilatation with Brockenbrough needle for
      severely calcified occlusion in superficial femoral artery.
AB  - A 75-year-old hemodialysis patient with right critical limb ischemia received
      endovascular therapy for a chronic total occlusion (CTO) in a diffusely calcified
      superficial femoral artery (SFA). During a retrograde approach, a Brockenbrough
      needle (BN) was able to penetrate the calcified hard plaque formed in the middle
      segment of the CTO. Moreover, bougie dilatation with the BN allowed balloon
      crossing and stent deployment, even after failure to pass a 2.0-mm monorail
      balloon across the plaque. These results suggest that the BN offers a new
      therapeutic option in the penetration and modification of severely calcified CTO
      in SFA. 

PMID- 23979908
TI  - In memoriam: Edmund Pellegrino (June 22, 1920-June 13, 2013).

PMID- 23979909
TI  - SEOM clinical guidelines for the systemic treatment of early breast cancer 2013.
AB  - The purpose of this article is to update our previous work on the treatment and
      follow-up in early breast cancer. In this new version we have classified a
      treatment by immunohistochemistry subtypes of breast cancer. Latest advances in
      the management of this disease have been compiled, either in the adjuvant and
      neoadjuvant setting or chemotherapy and hormonal treatment. This review is
      presented in an easy way for oncologist, fellows and for other specialties. 

PMID- 23979910
TI  - Comparison of tumor neovasculature-targeted paramagnetic nanoliposomes for MRI in
      mice xenograft models.
AB  - INTRODUCTION: Neovasculature imaging is a promising approach for tumor diagnosis.
      We constructed tumor neovasculature targeted paramagnetic nanoliposomes with
      RGD10, F56, and K237 peptides, which can bind to Integrin alphavbeta3 and VEGFR
      1, VEGFR-2, respectively, and compared their potential value as MRI contrast
      agents for detecting small tumors in animal models. MATERIALS AND METHODS:
      Peptide-Ahx-palmitic acid conjugate was synthesized using Fmoc solid-phase
      synthesis chemistry. Targeted paramagnetic nanoliposomes were prepared by the
      thin film dispersion-sonication method. The tumor signal enhancements of liposome
      particles were evaluated by MRI in a xenograft mice model. RESULTS: The apparent
      affinity constants of RGD10, K237, and F56 peptides binding to their cell
      receptors were 9.15 * 10(7), 6.01 * 10(7), and 3.85 * 10(7) mol/L, respectively.
      RGD10 and K237 targeted paramagnetic nanoliposomes have shown much greater tumor
      specific MRI signal enhancement in xenograft of the nude mice compared to F56
      targeted paramagnetic nanoliposome. Tumor signal enhancement rate (SER %)
      increased 2.21 +/- 0.09 and 1.82 +/- 0.05 fold, respectively, for RGD10 and K237
      compared to non-targeted control in T1 weighted MR image. CONCLUSION: RGD10 and
      K237 targeted paramagnetic nanoliposomes can be developed as potential tumor
      specific MRI contrast agents and are helpful for tumor detection.

PMID- 23979911
TI  - Serum integrin-linked kinase (sILK) concentration and survival in non-small cell
      lung cancer: a pilot study.
AB  - BACKGROUND: Integrin-linked kinase (ILK) is an intracellular signaling protein
      critically involved in cellular growth and motility. In non-small cell lung
      cancer (NSCLC), increased ILK expression has been associated with decreased
      recurrence-free and overall survival. Recently, ILK has also been detected in the
      serum of NSCLC patients. OBJECTIVE: To assess the prognostic impact of
      preoperative serum ILK (sILK) concentration on overall survival in surgically
      amenable NSCLC. PATIENTS AND METHODS: Preoperative sILK was quantified by ELISA
      in 50 newly diagnosed NSCLC patients. After surgery, patients were followed-up
      for a median interval of 2.5 years. RESULTS: Serum ILK concentrations ranged from
      0 to 2.44 ng/ml. Mean sILK was around 2.3 times higher in the 16 patients who
      died as compared to the 34 patients who survived (1.04 vs. 0.45 ng/ml, p =
      0.001). In univariate time-to-event analysis, increased sILK was associated with
      adverse survival [Hazard ratio (HR): 4.03, 95 % CI: 2.00-8.13, p < 0.001]. This
      association prevailed after multivariable adjustment for several clinical,
      demographic, and laboratory parameters (HR: 3.85, 95 % CI: 1.53-9.72, p = 0.004).
      CONCLUSIONS: Serum ILK shows potential as a novel strong and independent
      prognostic marker for postoperative survival in surgically amenable NSCLC.

PMID- 23979912
TI  - A 'tete-a tete' between cancer stem cells and endothelial progenitor cells in
      tumor angiogenesis.
AB  - Accumulating evidence suggests the involvement of stem cells in tumor
      angiogenesis. Two major types of stem cells frequently discussed in this regard
      are bone marrow-derived endothelial progenitor cells (EPCs) and tumor-derived
      cancer stem cells (CSCs). The present review discusses the possibility of a close
      association between these two cell types that drives the tumor towards
      metastasis. An exploration of this plausible relationship between EPCs and CSCs
      is imperative to completely unveil the mechanisms of tumor angiogenesis and
      develop CSC- and/or EPC-targeted anti-tumor therapies. 

PMID- 23979914
TI  - The Canadian methotrexate and etanercept outcome study: a randomised trial of
      discontinuing versus continuing methotrexate after 6 months of etanercept and
      methotrexate therapy in rheumatoid arthritis.
AB  - OBJECTIVE: To determine if withdrawing methotrexate (MTX) after 6 months of
      combination etanercept (ETN)+MTX, in MTX-inadequate responders with active
      rheumatoid arthritis (RA), is non-inferior to continuing ETN+MTX. METHODS: Tumour
      necrosis factor-inhibitor naive RA patients with disease activity score 28
      (DAS28)>=3.2, swollen joint count>=3, despite stable MTX, were treated with
      ETN+MTX for 6 months, followed by randomisation to either continue ETN+MTX or
      switch to ETN monotherapy for an additional 18 months. The primary endpoint was
      change in DAS28 from 6-month randomisation to 12 months. The non-inferiority
      margin of change in DAS28 was 0.6, with prespecified analyses (DAS28<3.2 vs
      DAS28>=3.2). RESULTS: 205 patients were randomised. DAS28 was stable in patients
      on ETN+MTX and increased slightly in patients on ETN monotherapy from 6 to 12
      months. Non-inferiority was not achieved, with an adjusted difference of 0.4 (0.1
      to 0.7) between the ETN and the ETN+MTX groups, for the month 6-12 change in
      DAS28. However, patients who achieved low disease activity (LDA; DAS28<3.2) at 6
      months had a similar disease activity at 12 months, whether on monotherapy or
      combination therapy (DAS28 change 0.7 ETN vs 0.57 ETN+MTX, p=0.8148). Conversely,
      for patients who did not reach LDA at 6 months, those on ETN monotherapy had
      increased disease activity at 12 months, while disease activity continued to
      decrease for patients on combination therapy, at 12 months (DAS28 change 0.4 ETN
      vs -0.4 ETN+MTX, p=0.0023). CONCLUSIONS: Non-inferiority was not achieved.
      Withdrawing MTX after 6 months of continuation ETN+MTX in MTX inadequate
      responders did not yield the same degree of improvement between 6 and 12 months
      compared with continuing ETN+MTX. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00654368.

PMID- 23979915
TI  - Uterine damage in swine following uterine artery embolization: comparison among
      gelatin sponge particles and two concentrations of N-butyl cyanoacrylate.
AB  - PURPOSE: To compare the degree of uterine damage caused by uterine artery
      embolization (UAE) with gelatin sponge particles (GSPs) and N-butyl cyanoacrylate
      (NBCA) in swine. MATERIALS AND METHODS: Fifteen swine were divided into three
      groups of five according to embolic material: group A (1-mm GSPs), group B
      (NBCA:Lipiodol = 1:1), and group C (NBCA:Lipiodol = 1:7). The uterine arteries
      were completely occluded bilaterally. The uteri were removed 3 days after
      embolization, and radiographs of the removed specimens were obtained in groups B
      and C to evaluate the distribution of the NBCA. The macroscopic necrosis rates of
      the uteri were calculated, and the uteri were evaluated histologically. RESULTS:
      Uterine necrosis rates were 4.9 +/- 6.1, 1.3 +/- 3.3, and 41.4 +/- 28.8 % in
      groups A, B, and C, respectively, and were significantly higher in group C than
      in groups A (p = 0.0014) and B (p < 0.001). Uterine necroses were found in all 9
      of the uteri with distal distributions of NBCA, and in only 1 of the 11 uteri
      with proximal distributions of NBCA. CONCLUSIONS: Dilute NBCA caused more damage
      to the uteri than GSPs and concentrated NBCA did. Distal embolization using NBCA
      caused large necroses. Therefore, proximal UAE using concentrated NBCA should be
      considered in clinical situations.

PMID- 23979916
TI  - Expression of efflux transporters in human ocular tissues.
AB  - To investigate the expression profiles of efflux transporters in human ocular
      tissues, quantitative real-time polymerase chain reaction, Western blotting, and
      immunohistochemistry were used to obtain the relative mRNA and protein
      expressions of various efflux transporters in human ocular tissues. The cornea,
      conjunctiva, iris-ciliary body (ICB), retina and choroid, human corneal
      epithelial cell line (HCEC), and human retinal pigment epithelial cell line (ARPE
      19) were examined for the expressions of multidrug resistance-associated proteins
      1-7 (MRP1-7), multidrug resistance 1 (MDR1) P-glycoprotein, lung resistance
      protein (LRP), and breast cancer-resistance protein (BCRP). The expression sites
      and patterns of efflux transporters were significantly different in ocular
      tissues, HCEC, and ARPE-19, as well as the expression profiles of efflux
      transporters in mRNA and protein levels in ocular tissues. At the protein level,
      MRP1-7, MDR1, and LRP were expressed in the corneal epithelium; MRP1-7, MDR1,
      LRP, and BCRP were expressed in the conjunctival epithelium; MRP1-2, MRP6-7,
      MDR1, and LRP were expressed in the ICB; MRP1-3, MRP6-7, MDR1, and LRP were
      expressed in the retina; MRP1-3, MRP6-7, MDR1, and LRP were expressed in the
      HCEC; and MRP7, MDR1, LRP, and BCRP were expressed in the ARPE-19. This
      quantitative and systematic study of efflux transporters in normal ocular tissues
      and cell lines provides evidence of cross-ocular tissue transporter expression
      differences, implying that efflux transporter expression variability should be
      taken into consideration for better understanding of ocular pharmacokinetic and
      pharmacodynamic data. 

PMID- 23979918
TI  - PARP1 is overexpressed in nasopharyngeal carcinoma and its inhibition enhances
      radiotherapy.
AB  - Nasopharyngeal carcinoma is a rare but highly invasive cancer. As options of
      agents for effective combination chemoradiotherapy for advanced nasopharyngeal
      carcinoma are limited, novel therapeutic approaches are desperately needed. The
      ubiquitin ligase CHFR is known to target PARP1 for degradation and is
      epigenetically inactivated in nasopharyngeal carcinoma. We present evidence that
      PARP1 protein is indeed overexpressed in nasopharyngeal carcinoma cells in
      comparison with immortalized normal nasopharyngeal epithelial cells. Tissue
      microarray analysis also indicated that PARP1 protein is significantly elevated
      in primary nasopharyngeal carcinoma tissues, with strong correlation with all
      stages of nasopharyngeal carcinoma development. We found that the PARP inhibitor
      AZD2281 (olaparib) increased DNA damage, cell-cycle arrest, and apoptosis in
      nasopharyngeal carcinoma cells challenged with ionizing radiation or
      temozolomide. Isobologram analysis confirmed that the cytotoxicity triggered by
      AZD2281 and DNA-damaging agents was synergistic. Finally, AZD2281 also enhanced
      the tumor-inhibitory effects of ionizing radiation in animal xenograft models.
      These observations implicate that PARP1 overexpression is an early event in
      nasopharyngeal carcinoma development and provide a molecular basis of using PARP
      inhibitors to potentiate treatment of nasopharyngeal carcinoma with radio- and
      chemotherapy.

PMID- 23979919
TI  - Capillary isoelectric-focusing immunoassays to study dynamic oncoprotein
      phosphorylation and drug response to targeted therapies in non-small cell lung
      cancer.
AB  - Developing proteomic biomarkers is valuable for evaluating therapeutic effects of
      drugs and generating better treatment strategies. However, conventional protein
      analysis is often challenging due to inadequate sample size of clinical
      specimens, lack of assay reproducibility, accuracy, and sensitivity. A novel
      capillary isoelectricfocusing (IEF) immunoassay system (NanoPro) was used to
      study the dynamic phosphorylation status of signaling molecules in non-small cell
      lung cancer (NSCLC) cells treated with EGFR tyrosine kinase and MEK inhibitors.
      NanoPro showed the same dynamic ERK phosphorylation as Western blotting with good
      assay reproducibility using 1,000 times less protein. The IEF separation in
      NanoPro system enables multiple protein phosphorylation isoforms to be resolved
      and detected simultaneously. With NanoPro, we identified a specific on-target
      mitogen-activated protein/extracellular signal-regulated kinase (MEK) response
      pattern to MEK inhibitor PD325901, which was not detectable by Western blot
      analysis. We also revealed a MEK2 signal that may be associated with NSCLC cell
      sensitivity to the EGF receptor inhibitor erlotinib, and distinguished erlotinib
      sensitive cells from intrinsic as well as acquired resistant cells to erlotinib.
      Moreover, NanoPro could differentiate human ERK1 isoforms from the mouse isoforms
      based on their isoelectric point differences and showed that erlotinib
      effectively inhibited ERK phosphorylation in targeted human xenograft cancer
      cells but not in surrounding mouse stromal cells. With 8 MUg of tumor aspirates,
      we precisely quantified the response of 18 signaling molecules to erlotinib and
      MEK1 inhibitor treatments in an NSCLC patient. NanoPro's higher sensitivity,
      better resolution of protein phosphorylation status, and reduced tissue
      requirement warrant NanoPro's investigation for future drug development and
      evaluation of drug effects of targeted therapies.

PMID- 23979920
TI  - Arginine deiminase resistance in melanoma cells is associated with metabolic
      reprogramming, glucose dependence, and glutamine addiction.
AB  - Many malignant human tumors, including melanomas, are auxotrophic for arginine
      due to reduced expression of argininosuccinate synthetase-1 (ASS1), the rate
      limiting enzyme for arginine biosynthesis. Pegylated arginine deiminase (ADI
      PEG20), which degrades extracellular arginine, resulting in arginine deprivation,
      has shown favorable results in clinical trials for treating arginine-auxotrophic
      tumors. Drug resistance is the major obstacle for effective ADI-PEG20 usage. To
      elucidate mechanisms of resistance, we established several ADI-PEG20-resistant
      (ADI(R)) variants from A2058 and SK-Mel-2 melanoma cells. Compared with the
      parental lines, these ADI(R) variants showed the following characteristics: (i)
      all ADI(R) cell lines showed elevated ASS1 expression, resulting from the
      constitutive binding of the transcription factor c-Myc on the ASS1 promoter,
      suggesting that elevated ASS1 is the major mechanism of resistance; (ii) the
      ADI(R) cell lines exhibited enhanced AKT signaling and were preferentially
      sensitive to PI3K/AKT inhibitors, but reduced mTOR signaling, and were
      preferentially resistant to mTOR inhibitor; (iii) these variants showed enhanced
      expression of glucose transporter-1 and lactate dehydrogenase-A, reduced
      expression of pyruvate dehydrogenase, and elevated sensitivity to the glycolytic
      inhibitors 2-deoxy-glucose and 3-bromopyruvate, consistent with the enhanced
      glycolytic pathway (the Warburg effect); (iv) the resistant cells showed higher
      glutamine dehydrogenase and glutaminase expression and were preferentially
      vulnerable to glutamine inhibitors. We showed that c-Myc, not elevated ASS1
      expression, is involved in upregulation of many of these enzymes because
      knockdown of c-Myc reduced their expression, whereas overexpressed ASS1 by
      transfection reduced their expression. This study identified multiple targets for
      overcoming ADI-PEG resistance in cancer chemotherapy using recombinant arginine
      degrading enzymes.

PMID- 23979921
TI  - Attenuation of argininosuccinate lyase inhibits cancer growth via cyclin A2 and
      nitric oxide.
AB  - Arginine biosynthesis and nitric oxide (NO) production are important for cancer
      homeostasis. Degradation of arginine may be used to inhibit liver tumors with low
      argininosuccinate synthetase (ASS) expression. In this report, we investigated an
      alternative therapeutic approach by targeting argininosuccinate lyase (ASL). ASL
      is transcriptionally induced by endoplasmic reticulum stress and is overexpressed
      in some human liver tumors. Knockdown of ASL expression by short hairpin RNA
      (shRNA) in three liver cancer cell lines, ML-1, HuH-7, and HepG2, decreased
      colony formation in vitro and tumor growth in vivo. Furthermore, lentiviral
      infection of ASL shRNA inhibited tumor growth in a therapeutic animal tumor
      model. Analysis of ASL shRNA on the cell-cycle progression revealed a G2-M delay.
      Among cell-cycle regulatory molecules, cyclin A2 expression was reduced.
      Reintroduction of exogenous cyclin A2 restored the cell growth in ASL-knockdown
      cells. Autophagy was observed in the cells treated with ASL shRNA, as shown by an
      increase in LC3-II levels and autophagosome formation. The total cellular
      arginine level was not altered significantly. Inhibition of autophagy further
      attenuated cell growth, suggesting that autophagy induced by ASL shRNA plays a
      feedback prosurvival function. Knockdown of ASL reduced NO content, and addition
      of NO donor partially recovered the growth inhibition by ASL shRNA. In summary,
      downregulation of ASL attenuated tumor growth and the inhibition was mainly
      mediated by a decrease of cyclin A2 and NO.

PMID- 23979922
TI  - Increase of pro-oxidants with no evidence of lipid peroxidation in exhaled breath
      condensate after a 10-km race in non-athletes.
AB  - It is a well-established fact that exercise increases pro-oxidants and favors
      oxidative stress; however, this phenomenon has been poorly studied in human
      lungs. Pro-oxidative generation (H(2)O(2), NO(2) (-)), lipid peroxidation markers
      (MDA), and inflammation (pH) in exhaled breath condensate (EBC) have been
      determined through data from 10 active subjects who ran 10 km; samples were
      obtained immediately before, at 20, and at 80 min post-exertion. In EBC, the
      concentration of H(2)O(2) at 80 min post-exertion was increased. NO(2) (-)
      concentration showed a tendency to increase at 80 min post-exertion, with no
      variations in MDA and pH. No variations of NO(2) (-) were found in plasma, while
      there was an increase of NO(2) (-) at 80 min post-exertion in the relation
      between EBC and plasma. NO(2) (-) in EBC did not correlate to plasmatic NO(2) (
      ), while it did correlate directly with H(2)O(2) in EBC, suggesting a localized
      origin for the exercise-related NO(2) (-) increase in EBC. MDA in plasma did not
      increase nor correlate with MDA in EBC. In conclusion, high-intensity exercise
      increases lung-originated pro-oxidants in non-athlete subjects with no evidence
      of early lipid peroxidation and changes in the pH value in EBC.

PMID- 23979924
TI  - Iron stores in low and normal birth weight infants at birth and in early infancy.
AB  - Serum ferritin levels of low birth weight (LBW; BW < 2,500 g) and normal birth
      weight (NBW; BW >= 2,500 g) infants were evaluated at birth and at 3 mo using
      electrochemiluminescence immunoassay. At birth, levels were 318.6 (31.0-829.5)
      ng/mL in LBW (n = 217) and 366.2 (122.4-858.5) ng/mL in NBW infants (n = 116; p <
      0.01), with 1.4 % of LBW and none of the NBW infants having levels <12 ng/mL (p =
      0.20). At follow up, levels were 66.9 (4.5-567.7) ng/mL in LBW (n = 126) and
      126.2 (6.8-553.7) ng/mL in NBW infants (n = 76; p = 0.27), with 11.9 % of LBW and
      11.8 % of NBW infants having levels <12 ng/mL (p = 0.80). 

PMID- 23979923
TI  - The John Insall Award: A minimum 10-year outcome study of autologous chondrocyte
      implantation.
AB  - BACKGROUND: Autologous chondrocyte implantation (ACI) has demonstrated good and
      excellent results in over 75% of patients up to 10 years after surgery. Reports
      of longer-term outcomes, however, remain limited. QUESTIONS/PURPOSES: The
      purposes of this study were to describe the (1) survivorship of ACI grafts; (2)
      the long-term functional outcomes using validated scoring tools after ACI; and
      (3) to provide an analysis of potential predictors for failure. METHODS: Two
      hundred ten patients treated with ACI were followed for more than 10 years.
      Indications for the procedure included symptomatic cartilage defects in all
      compartments of the knee unresponsive to nonoperative measures. Mean age at
      surgery was 36 +/- 9 years; mean defect size measured 8.4 +/- 5.5 cm(2). Outcome
      scores were prospectively collected pre- and postoperatively at the last
      followup. RESULTS: At a mean of 12 +/- 2 years followup, 53 of 210 patients (25%)
      had at least one failed ACI graft. Nineteen of these patients went on to
      arthroplasty, 27 patients were salvaged with revision cartilage repair, and seven
      patients declined further treatment; three patients were lost to followup. The
      modified Cincinnati increased from 3.9 +/- 1.5 to 6.4 +/- 1.5, WOMAC improved
      from 39 +/- 21 to 23 +/- 16, Knee Society Score (KSS) knee score rose from 54 +/-
      18 to 79 +/- 19, and KSS function from 65 +/- 23 to 78 +/- 17 (all p < 0.0001).
      The Physical Component of the SF-36 score increased from 33 +/- 14 to 49 +/- 18,
      whereas the Mental Component improved from 46 +/- 14 to 52 +/- 15 (both p <
      0.001). Survivorship was higher in patients with complex versus salvage-type
      lesions (p = 0.03) with primary ACI versus ACI after prior marrow stimulation (p
      = 0.004) and with concomitant high tibial osteotomy (HTO) versus no HTO (p =
      0.01). CONCLUSIONS: ACI provided durable outcomes with a survivorship of 71% at
      10 years and improved function in 75% of patients with symptomatic cartilage
      defects of the knee at a minimum of 10 years after surgery. A history of prior
      marrow stimulation as well as the treatment of very large defects was associated
      with an increased risk of failure.

PMID- 23979926
TI  - Electrotherapy for neck pain.
AB  - BACKGROUND: Neck pain is common, disabling and costly. The effectiveness of
      electrotherapy as a physiotherapeutic option remains unclear. This is an update
      of a Cochrane review first published in 2005 and previously updated in 2009.
      OBJECTIVES: This systematic review assessed the short, intermediate and long-term
      effects of electrotherapy on pain, function, disability, patient satisfaction,
      global perceived effect, and quality of life in adults with neck pain with and
      without radiculopathy or cervicogenic headache. SEARCH METHODS: We searched
      CENTRAL, MEDLINE, EMBASE, MANTIS, CINAHL, and ICL, without language restrictions,
      from their beginning to August 2012; handsearched relevant conference
      proceedings; and consulted content experts. SELECTION CRITERIA: Randomized
      controlled trials (RCTs), in any language, investigating the effects of
      electrotherapy used primarily as unimodal treatment for neck pain. Quasi-RCTs and
      controlled clinical trials were excluded. DATA COLLECTION AND ANALYSIS: We used
      standard methodological procedures expected by The Cochrane Collaboration. We
      were unable to statistically pool any of the results, but we assessed the quality
      of the evidence using an adapted GRADE approach. MAIN RESULTS: Twenty small
      trials (1239 people with neck pain) containing 38 comparisons were included.
      Analysis was limited by trials of varied quality, heterogeneous treatment
      subtypes and conflicting results. The main findings for reduction of neck pain by
      treatment with electrotherapeutic modalities were as follows.Very low quality
      evidence determined that pulsed electromagnetic field therapy (PEMF) and
      repetitive magnetic stimulation (rMS) were more effective than placebo, while
      transcutaneous electrical nerve stimulation (TENS) showed inconsistent
      results.Very low quality evidence determined that PEMF, rMS and TENS were more
      effective than placebo.Low quality evidence (1 trial, 52 participants) determined
      that permanent magnets (necklace) were no more effective than placebo
      (standardized mean difference (SMD) 0.27, 95% CI -0.27 to 0.82, random-effects
      model).Very low quality evidence showed that modulated galvanic current,
      iontophoresis and electric muscle stimulation (EMS) were not more effective than
      placebo.There were four trials that reported on other outcomes such as function
      and global perceived effects, but none of the effects were of clinical
      importance. When TENS, iontophoresis and PEMF were compared to another treatment,
      very low quality evidence prevented us from suggesting any recommendations. No
      adverse side effects were reported in any of the included studies. AUTHORS'
      CONCLUSIONS: We cannot make any definite statements on the efficacy and clinical
      usefulness of electrotherapy modalities for neck pain. Since the evidence is of
      low or very low quality, we are uncertain about the estimate of the effect.
      Further research is very likely to change both the estimate of effect and our
      confidence in the results. Current evidence for PEMF, rMS, and TENS shows that
      these modalities might be more effective than placebo. When compared to other
      interventions the quality of evidence was very low thus preventing further
      recommendations.Funding bias should be considered, especially in PEMF studies.
      Galvanic current, iontophoresis, EMS, and a static magnetic field did not reduce
      pain or disability. Future trials on these interventions should have larger
      patient samples, include more precise standardization, and detail treatment
      characteristics.

PMID- 23979925
TI  - Safety of bevacizumab in treating metastatic colorectal cancer: a systematic
      review and meta-analysis of all randomized clinical trials.
AB  - BACKGROUND AND OBJECTIVE: The incidence rates of colorectal cancer (CRC) are
      increasing in a number of different regions, and recent studies have indicated
      that addition of bevacizumab to CRC therapy is beneficial. To better understand
      the relative risk (RR) of adverse events associated with use of bevacizumab, we
      systematically reviewed published clinical trials that studied use of bevacizumab
      in treatment of patients affected by metastatic CRC (mCRC). METHODS: The National
      Library of Medicine PubMed, MEDLINE, Ovid, Cochrane Library and Chinese
      Biomedicine databases were searched. The RR and number needed to harm (NNH)
      values for major side effects with 95% confidence intervals (CIs) were calculated
      in a fixed-effects model and a random-effects model, where appropriate. RESULTS:
      Fifteen controlled trials totalling 6,937 patients were eligible for this
      analysis. Compared with the control group, the bevacizumab treatment group had a
      slightly higher risk of any severe adverse event (pooled RR 1.07 [95% CI 1.02
      1.12]). The pooled risk difference was 5% [95% CI 2-9%], with an NNH of 20
      treated patients. Analyses showed a statistically significantly higher risk of
      secondary endpoints, including the discovery that bevacizumab was associated with
      a threefold higher risk of hypertension (pooled RR 3.06 [95% CI 2.45-3.83]), a
      twofold higher risk of gastrointestinal haemorrhage/perforation and a lower risk
      of neutropenia (pooled RR 0.75 [95% CI 0.26-2.19]). CONCLUSION: Bevacizumab has
      efficacy in all treatment regimens for advanced CRC. However, our meta-analysis
      raises safety concerns regarding an increased risk of serious adverse events
      associated with use of bevacizumab among patients with mCRC. Our findings warrant
      cautious use of bevacizumab in clinical oncology.

PMID- 23979927
TI  - Fifteen-minute consultation: Troublesome crying in infancy.
AB  - There is much written in the medical and lay literature about managing babies who
      cry too much. Healthcare professional often feel bewildered about how to go about
      trying to help a baby and their carer, usually the mother. They often undertake
      investigations, prescribe medication or alter the baby's diet. The assumption
      made by this approach is that the crying reflects pain or discomfort. In a normal
      infant who is growing well, it is rare to be able to identify any quickly
      treatable medical underlying disorder. Those who are inexperienced may find the
      idea of a behavioural approach very challenging but perhaps this would be a
      better alternative.

PMID- 23979928
TI  - Comparing zinc finger nucleases and transcription activator-like effector
      nucleases for gene targeting in Drosophila.
AB  - Zinc-finger nucleases have proven to be successful as reagents for targeted
      genome manipulation in Drosophila melanogaster and many other organisms. Their
      utility has been limited, however, by the significant failure rate of new
      designs, reflecting the complexity of DNA recognition by zinc fingers.
      Transcription activator-like effector (TALE) DNA-binding domains depend on a
      simple, one-module-to-one-base-pair recognition code, and they have been very
      productively incorporated into nucleases (TALENs) for genome engineering. In this
      report we describe the design of TALENs for a number of different genes in
      Drosophila, and we explore several parameters of TALEN design. The rate of
      success with TALENs was substantially greater than for zinc-finger nucleases ,
      and the frequency of mutagenesis was comparable. Knockout mutations were isolated
      in several genes in which such alleles were not previously available. TALENs are
      an effective tool for targeted genome manipulation in Drosophila. 

PMID- 23979929
TI  - Characterization of two ENU-induced mutations affecting mouse skeletal
      morphology.
AB  - Using the N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we have identified two
      skeletal morphology mutants, Skm1 and Skm2. Positional cloning and candidate gene
      sequencing localized the causative point mutations within the genes coding for
      natriuretic peptide receptor C (NPR-C) and filamin b (FLNB), respectively. Mice
      that carry a mutation in Npr3 exhibit a skeletal overgrowth phenotype, resulting
      in an elongated body and kyphosis. Skm2 mice, carrying a mutation in Flnb,
      present with scoliosis and lordosis. These mutant mice will serve as useful
      models for the study of vertebral malformations. 

PMID- 23979930
TI  - Global linkage map connects meiotic centromere function to chromosome size in
      budding yeast.
AB  - Synthetic genetic array (SGA) analysis automates yeast genetics, enabling high
      throughput construction of ordered arrays of double mutants. Quantitative colony
      sizes derived from SGA analysis can be used to measure cellular fitness and score
      for genetic interactions, such as synthetic lethality. Here we show that SGA
      colony sizes also can be used to obtain global maps of meiotic recombination
      because recombination frequency affects double-mutant formation for gene pairs
      located on the same chromosome and therefore influences the size of the resultant
      double-mutant colony. We obtained quantitative colony size data for ~1.2 million
      double mutants located on the same chromosome and constructed a genome-scale
      genetic linkage map at ~5 kb resolution. We found that our linkage map is
      reproducible and consistent with previous global studies of meiotic
      recombination. In particular, we confirmed that the total number of crossovers
      per chromosome tends to follow a simple linear model that depends on chromosome
      size. In addition, we observed a previously unappreciated relationship between
      the size of linkage regions surrounding each centromere and chromosome size,
      suggesting that crossovers tend to occur farther away from the centromere on
      larger chromosomes. The pericentric regions of larger chromosomes also appeared
      to load larger clusters of meiotic cohesin Rec8, and acquire fewer Spo11
      catalyzed DNA double-strand breaks. Given that crossovers too near or too far
      from centromeres are detrimental to homolog disjunction and increase the
      incidence of aneuploidy, our data suggest that chromosome size may have a direct
      role in regulating the fidelity of chromosome segregation during meiosis. 

PMID- 23979931
TI  - Disruption of the rice plastid ribosomal protein s20 leads to chloroplast
      developmental defects and seedling lethality.
AB  - Plastid ribosomal proteins (PRPs) are essential for ribosome biogenesis, plastid
      protein biosynthesis, chloroplast differentiation, and early chloroplast
      development. This study identifies the first rice PRP mutant, asl1 (albino
      seedling lethality1), which exhibits an albino lethal phenotype at the seedling
      stage. This albino phenotype was associated with altered chlorophyll (Chl)
      content and chloroplast development. Map-based cloning revealed that ASL1 encodes
      PRP S20 (PRPS20), which localizes to the chloroplast. ASL1 showed tissue-specific
      expression, as it was highly expressed in plumule and young seedlings but
      expressed at much lower levels in other tissues. In addition, ASL1 expression was
      regulated by light. The transcript levels of nuclear genes for Chl biosynthesis
      and chloroplast development were strongly affected in asl1 mutants; transcripts
      of some plastid genes for photosynthesis were undetectable. Our findings indicate
      that nuclear-encoded PRPS20 plays an important role in chloroplast development in
      rice. 

PMID- 23979932
TI  - The Drosophila enhancer of split gene complex: architecture and coordinate
      regulation by notch, cohesin, and polycomb group proteins.
AB  - The cohesin protein complex functionally interacts with Polycomb group (PcG)
      silencing proteins to control expression of several key developmental genes, such
      as the Drosophila Enhancer of split gene complex [E(spl)-C]. The E(spl)-C
      contains 12 genes that inhibit neural development. In a cell line derived from
      the central nervous system, cohesin and the PRC1 PcG protein complex bind and
      repress E (spl)-C transcription, but the repression mechanisms are unknown. The
      genes in the E(spl)-C are directly activated by the Notch receptor. Here we show
      that depletion of cohesin or PRC1 increases binding of the Notch intracellular
      fragment to genes in the E(spl)-C, correlating with increased transcription. The
      increased transcription likely reflects both direct effects of cohesin and PRC1
      on RNA polymerase activity at the E(spl)-C, and increased expression of Notch
      ligands. By chromosome conformation capture we find that the E(spl)-C is
      organized into a self-interactive architectural domain that is co-extensive with
      the region that binds cohesin and PcG complexes. The self-interactive
      architecture is formed independently of cohesin or PcG proteins. We posit that
      the E(spl)-C architecture dictates where cohesin and PcG complexes bind and act
      when they are recruited by as yet unidentified factors, thereby controlling the
      E(spl)-C as a coordinated domain. 

PMID- 23979933
TI  - Imputation-based genomic coverage assessments of current human genotyping arrays.
AB  - Microarray single-nucleotide polymorphism genotyping, combined with imputation of
      untyped variants, has been widely adopted as an efficient means to interrogate
      variation across the human genome. "Genomic coverage" is the total proportion of
      genomic variation captured by an array, either by direct observation or through
      an indirect means such as linkage disequilibrium or imputation. We have performed
      imputation-based genomic coverage assessments of eight current genotyping arrays
      that assay from ~0.3 to ~5 million variants. Coverage was determined separately
      in each of the four continental ancestry groups in the 1000 Genomes Project phase
      1 release. We used the subset of 1000 Genomes variants present on each array to
      impute the remaining variants and assessed coverage based on correlation between
      imputed and observed allelic dosages. More than 75% of common variants (minor
      allele frequency > 0.05) are covered by all arrays in all groups except for
      African ancestry, and up to ~90% in all ancestries for the highest density
      arrays. In contrast, less than 40% of less common variants (0.01 < minor allele
      frequency < 0.05) are covered by low density arrays in all ancestries and 50-80%
      in high density arrays, depending on ancestry. We also calculated genome-wide
      power to detect variant-trait association in a case-control design, across
      varying sample sizes, effect sizes, and minor allele frequency ranges, and
      compare these array-based power estimates with a hypothetical array that would
      type all variants in 1000 Genomes. These imputation-based genomic coverage and
      power analyses are intended as a practical guide to researchers planning genetic
      studies. 

PMID- 23979934
TI  - Identification of genes interacting with rnt-1 through large-scale RNAi screening
      in Caenorhabditis elegans.
AB  - Although many critical roles of the RUNX family proteins have already been
      identified, little attention has been given to how these proteins interact with
      other factors. Elucidating RUNX protein interactions will help extend our
      understanding of their roles in normal development and tumorigenesis. In this
      study, we performed large-scale RNAi screening to identify genes that genetically
      interact with rnt-1, the sole homolog of RUNX protein in the nematode
      Caenorhabditis elegans. To this end, we took advantage of the fact that C.
      elegans can survive a severe loss of RNT-1 function with only mild phenotypes,
      and we looked for genes that caused a synthetic phenotype in the rnt-1 mutant
      background. We identified seven genes, three of which (cdk-8, cic-1, and sur-2)
      are involved in transcription, two of which (pgp-2 and cct-5) are involved in
      stress response, and two of which (D2045.7 and W09D10.4) are involved in
      signaling cascades, according to their functional gene ontology terms. We further
      confirmed that the CDK8-containing mediator complex genetically interacts with
      RNT-1 by showing that knockdown of each component of the CDK8 mediator complex
      caused a synthetic phenotype, that is, the exploded intestine through the vulva
      (Eiv) phenotype, in the rnt-1 mutant background. We also identified a putative
      target gene, acs-4, which is regulated by the RNT-1 and CDK8 mediator complex.
      Our results strengthen the notion that the CDK8 mediator complex may also act
      together with RUNX proteins in mammals. 

PMID- 23979935
TI  - Insights into the evolution of cotton diploids and polyploids from whole-genome
      re-sequencing.
AB  - Understanding the composition, evolution, and function of the Gossypium hirsutum
      (cotton) genome is complicated by the joint presence of two genomes in its
      nucleus (AT and DT genomes). These two genomes were derived from progenitor A
      genome and D-genome diploids involved in ancestral allopolyploidization. To
      better understand the allopolyploid genome, we re-sequenced the genomes of extant
      diploid relatives that contain the A1 (Gossypium herbaceum), A2 (Gossypium
      arboreum), or D5 (Gossypium raimondii) genomes. We conducted a comparative
      analysis using deep re-sequencing of multiple accessions of each diploid species
      and identified 24 million SNPs between the A-diploid and D-diploid genomes. These
      analyses facilitated the construction of a robust index of conserved SNPs between
      the A-genomes and D-genomes at all detected polymorphic loci. This index is
      widely applicable for read mapping efforts of other diploid and allopolyploid
      Gossypium accessions. Further analysis also revealed locations of putative
      duplications and deletions in the A-genome relative to the D-genome reference
      sequence. The approximately 25,400 deleted regions included more than 50%
      deletion of 978 genes, including many involved with starch synthesis. In the
      polyploid genome, we also detected 1,472 conversion events between homoeologous
      chromosomes, including events that overlapped 113 genes. Continued
      characterization of the Gossypium genomes will further enhance our ability to
      manipulate fiber and agronomic production of cotton. 

PMID- 23979936
TI  - Drosophila embryonic cell-cycle mutants.
AB  - Nearly all cell division mutants in Drosophila were recovered in late
      larval/pupal lethal screens, with less than 10 embryonic lethal mutants
      identified, because larval development occurs without a requirement for cell
      division. Only cells in the nervous system and the imaginal cells that generate
      the adult body divide during larval stages, with larval tissues growing by
      increasing ploidy rather than cell number. Thus, most mutants perturbing mitosis
      or the cell cycle do not manifest a phenotype until the adult body differentiates
      in late larval and pupal stages. To identify cell-cycle components whose maternal
      pools are depleted in embryogenesis or that have specific functions in
      embryogenesis, we screened for mutants defective in cell division during
      embryogenesis. Five new alleles of Cyclin E were recovered, ranging from a
      missense mutation that is viable to stop codons causing embryonic lethality.
      These permitted us to investigate the requirements for Cyclin E function in
      neuroblast cell fate determination, a role previously shown for a null Cyclin E
      allele. The mutations causing truncation of the protein affect cell fate of the
      NB6-4 neuroblast, whereas the weak missense mutation has no effect. We identified
      mutations in the pavarotti (pav) and tumbleweed (tum) genes needed for
      cytokinesis by a phenotype of large and multinucleate cells in the embryonic
      epidermis and nervous system. Other mutations affecting the centromere protein
      CAL1 and the kinetochore protein Spc105R caused mitotic defects in the nervous
      system. 

PMID- 23979937
TI  - Genetic architecture of parallel pelvic reduction in ninespine sticklebacks.
AB  - Teleost fish genomes are known to be evolving faster than those of other
      vertebrate taxa. Thus, fish are suited to address the extent to which the same
      vs. different genes are responsible for similar phenotypic changes in rapidly
      evolving genomes of evolutionary independent lineages. To gain insights into the
      genetic basis and evolutionary processes behind parallel phenotypic changes
      within and between species, we identified the genomic regions involved in pelvic
      reduction in Northern European ninespine sticklebacks (Pungitius pungitius) and
      compared them to those of North American ninespine and threespine sticklebacks
      (Gasterosteus aculeatus). To this end, we conducted quantitative trait locus
      (QTL) mapping using 283 F2 progeny from an interpopulation cross. Phenotypic
      analyses indicated that pelvic reduction is a recessive trait and is inherited in
      a simple Mendelian fashion. Significant QTL for pelvic spine and girdle lengths
      were identified in the region of the Pituitary homeobox transcription factor 1
      (Pitx1) gene, also responsible for pelvic reduction in threespine sticklebacks.
      The fact that no QTL was observed in the region identified in the mapping study
      of North American ninespine sticklebacks suggests that an alternative QTL for
      pelvic reduction has emerged in this species within the past 1.6 million years
      after the split between Northern European and North American populations. In
      general, our study provides empirical support for the view that alternative
      genetic mechanisms that lead to similar phenotypes can evolve over short
      evolutionary time scales. 

PMID- 23979938
TI  - Identification of a novel polymorphism in X-linked sterol-4-alpha-carboxylate 3
      dehydrogenase (Nsdhl) associated with reduced high-density lipoprotein
      cholesterol levels in I/LnJ mice.
AB  - Loci controlling plasma lipid concentrations were identified by performing a
      quantitative trait locus analysis on genotypes from 233 mice from a F2 cross
      between KK/HlJ and I/LnJ, two strains known to differ in their high-density
      lipoprotein (HDL) cholesterol levels. When fed a standard diet, HDL cholesterol
      concentration was affected by two significant loci, the Apoa2 locus on Chromosome
      (Chr) 1 and a novel locus on Chr X, along with one suggestive locus on Chr 6. Non
      HDL concentration also was affected by loci on Chr 1 and X along with a
      suggestive locus on Chr 3. Additional loci that may be sex-specific were
      identified for HDL cholesterol on Chr 2, 3, and 4 and for non-HDL cholesterol on
      Chr 5, 7, and 14. Further investigation into the potential causative gene on Chr
      X for reduced HDL cholesterol levels revealed a novel, I/LnJ-specific
      nonsynonymous polymorphism in Nsdhl, which codes for sterol-4-alpha-carboxylate 3
      dehydrogenase in the cholesterol synthesis pathway. Although many lipid
      quantitative trait locus have been reported previously, these data suggest there
      are additional genes left to be identified that control lipid levels and that can
      provide new pharmaceutical targets. 

PMID- 23979939
TI  - Efficient single-cell transgene induction in Caenorhabditis elegans using a
      pulsed infrared laser.
AB  - The coupling of transgenes to heat shock promoters is a widely applied method for
      regulating gene expression. In C. elegans, gene induction can be controlled
      temporally through timing of heat shock and spatially via targeted rescue in heat
      shock mutants. Here, we present a method for evoking gene expression in arbitrary
      cells, with single-cell resolution. We use a focused pulsed infrared laser to
      locally induce a heat shock response in specific cells. Our method builds on and
      extends a previously reported method using a continuous-wave laser. In our
      technique, the pulsed laser illumination enables a much higher degree of spatial
      selectivity because of diffusion of heat between pulses. We apply our method to
      induce transient and long-term transgene expression in embryonic, larval, and
      adult cells. Our method allows highly selective spatiotemporal control of
      transgene expression and is a powerful tool for model organism biology. 

PMID- 23979940
TI  - When females produce sperm: genetics of C. elegans hermaphrodite reproductive
      choice.
AB  - Reproductive behaviors have manifold consequences on evolutionary processes.
      Here, we explore mechanisms underlying female reproductive choice in the nematode
      Caenorhabditis elegans, a species in which females have evolved the ability to
      produce their own self-fertilizing sperm, thereby allowing these "hermaphrodites"
      the strategic choice to self-reproduce or outcross with males. We report that
      hermaphrodites of the wild-type laboratory reference strain N2 favor self
      reproduction, whereas a wild isolate CB4856 (HW) favors outcrossing. To
      characterize underlying neural mechanisms, we show that N2 hermaphrodites
      deficient in mechanosensation or chemosensation (e.g., mec-3 and osm-6 mutants)
      exhibit high mating frequency, implicating hermaphrodite perception of males as a
      requirement for low mating frequency. Within chemosensory networks, we find
      opposing roles for different sets of neurons that express the cyclic GMP-gated
      nucleotide channel, suggesting both positive and negative sensory-mediated
      regulation of hermaphrodite mating frequency. We also show that the ability to
      self-reproduce negatively regulates hermaphrodite mating. To map genetic
      variation, we created recombinant inbred lines and identified two QTL that
      explain a large portion of N2 * HW variation in hermaphrodite mating frequency.
      Intriguingly, we further show that ~40 wild isolates representing C. elegans
      global diversity exhibit extensive and continuous variation in hermaphrodite
      reproductive outcome. Together, our findings demonstrate that C. elegans
      hermaphrodites actively regulate the choice between selfing and crossing,
      highlight the existence of natural variation in hermaphrodite choice, and lay the
      groundwork for molecular dissection of this evolutionarily important trait. 

PMID- 23979941
TI  - Practical considerations regarding the use of genotype and pedigree data to model
      relatedness in the context of genome-wide association studies.
AB  - Genome-wide association studies of complex traits often are complicated by
      relatedness among individuals. Ignoring or inappropriately accounting for
      relatedness often results in inflated type I error rates. Either genotype or
      pedigree data can be used to estimate relatedness for use in mixed-models when
      undertaking quantitative trait locus mapping. We performed simulations to
      investigate methods for controlling type I error and optimizing power considering
      both full and partial pedigrees and, similarly, both sparse and dense marker
      coverage; we also examined real data sets. (1) When marker density was low,
      estimating relatedness by genotype data alone failed to control the type I error
      rate; (2) this was resolved by combining both genotype and pedigree data. (3)
      When sufficiently dense marker data were used to estimate relatedness, type I
      error was well controlled and power increased; however, (4) this was only true
      when the relatedness was estimated using genotype data that excluded genotypes on
      the chromosome currently being scanned for a quantitative trait locus. 

PMID- 23979942
TI  - Functional conservation of Gsdma cluster genes specifically duplicated in the
      mouse genome.
AB  - Mouse Gasdermin A3 (Gsdma3) is the causative gene for dominant skin mutations
      exhibiting alopecia. Mouse has two other Gsdma3-related genes, Gsdma and Gsdma2,
      whereas human and rat have only one related gene. To date, no skin mutation has
      been reported for human GSDMA and rat Gsdma as well as mouse Gsdma and Gsdma2.
      Therefore, it is possible that only Gsdma3 has gain-of-function type mutations to
      cause dominant skin phenotype. To elucidate functional divergence among the Gsdma
      related genes in mice, and to infer the function of the human and rat orthologs,
      we examined in vivo function of mouse Gsdma by generating Gsdma knockout mice and
      transgenic mice that overexpress wild-type Gsdma or Gsdma harboring a point
      mutation (Alanine339Threonine). The Gsdma knockout mice shows no visible
      phenotype, indicating that Gsdma is not essential for differentiation of
      epidermal cells and maintenance of the hair cycle, and that Gsdma is expressed
      specifically both in the inner root sheath of hair follicles and in suprabasal
      cell layers, whereas Gsdma3 is expressed only in suprabasal layers. By contrast,
      both types of the transgenic mice exhibited epidermal hyperplasia resembling the
      Gsdma3 mutations, although the phenotype depended on the genetic background.
      These results indicate that the mouse Gsdma and Gsdma3 genes share common
      function to regulate epithelial maintenance and/or homeostasis, and suggest that
      the function of human GSDMA and rat Gsdma, which are orthologs of mouse Gsdma, is
      conserved as well. 

PMID- 23979943
TI  - Targeted deletion and inversion of tandemly arrayed genes in Arabidopsis thaliana
      using zinc finger nucleases.
AB  - Tandemly arrayed genes (TAGs) or gene clusters are prevalent in higher eukaryotic
      genomes. For example, approximately 17% of genes are organized in tandem in the
      model plant Arabidopsis thaliana. The genetic redundancy created by TAGs presents
      a challenge for reverse genetics. As molecular scissors, engineered zinc finger
      nucleases (ZFNs) make DNA double-strand breaks in a sequence-specific manner.
      ZFNs thus provide a means to delete TAGs by creating two double-strand breaks in
      the gene cluster. Using engineered ZFNs, we successfully targeted seven genes
      from three TAGs on two Arabidopsis chromosomes, including the well-known RPP4
      gene cluster, which contains eight resistance (R) genes. The resulting gene
      cluster deletions ranged from a few kb to 55 kb with frequencies approximating 1%
      in somatic cells. We also obtained large chromosomal deletions of ~9 Mb at
      approximately one tenth the frequency, and gene cluster inversions and
      duplications also were achieved. This study demonstrates the ability to use
      sequence-specific nucleases in plants to make targeted chromosome rearrangements
      and create novel chimeric genes for reverse genetics and biotechnology. 

PMID- 23979944
TI  - Targeted mutagenesis of Arabidopsis thaliana using engineered TAL effector
      nucleases.
AB  - Custom TAL effector nucleases (TALENs) are increasingly used as reagents to
      manipulate genomes in vivo. Here, we used TALENs to modify the genome of the
      model plant, Arabidopsis thaliana. We engineered seven TALENs targeting five
      Arabidopsis genes, namely ADH1, TT4, MAPKKK1, DSK2B, and NATA2. In pooled
      seedlings expressing the TALENs, we observed somatic mutagenesis frequencies
      ranging from 2-15% at the intended targets for all seven TALENs. Somatic
      mutagenesis frequencies as high as 41-73% were observed in individual transgenic
      plant lines expressing the TALENs. Additionally, a TALEN pair targeting a
      tandemly duplicated gene induced a 4.4-kb deletion in somatic cells. For the most
      active TALEN pairs, namely those targeting ADH1 and NATA2, we found that TALEN
      induced mutations were transmitted to the next generation at frequencies of 1.5
      12%. Our work demonstrates that TALENs are useful reagents for achieving targeted
      mutagenesis in this important plant model. 

PMID- 23979945
TI  - A whole-genome DNA marker map for cotton based on the D-genome sequence of
      Gossypium raimondii L.
AB  - We constructed a very-high-density, whole-genome marker map (WGMM) for cotton by
      using 18,597 DNA markers corresponding to 48,958 loci that were aligned to both a
      consensus genetic map and a reference genome sequence. The WGMM has a density of
      one locus per 15.6 kb, or an average of 1.3 loci per gene. The WGMM was anchored
      by the use of colinear markers to a detailed genetic map, providing
      recombinational information. Mapped markers occurred at relatively greater
      physical densities in distal chromosomal regions and lower physical densities in
      the central regions, with all 1 Mb bins having at least nine markers. Hotspots
      for quantitative trait loci and resistance gene analog clusters were aligned to
      the map and DNA markers identified for targeting of these regions of high
      practical importance. Based on the cotton D genome reference sequence, the
      locations of chromosome structural rearrangements plotted on the map facilitate
      its translation to other Gossypium genome types. The WGMM is a versatile genetic
      map for marker assisted breeding, fine mapping and cloning of genes and
      quantitative trait loci, developing new genetic markers and maps, genome-wide
      association mapping, and genome evolution studies. 

PMID- 23979946
TI  - Isolation and characterization of phytotoxic compounds produced by Streptomyces
      sp. AMC 23 from red mangrove (Rhizophora mangle).
AB  - Natural products produced by microorganisms have been utilized as sources of new
      drugs possessing a wide range of agrochemical and pharmacological activities.
      During our research on Actinomycetes from Brazilian mangroves, the ethyl acetate
      extract of Streptomyces sp. AMC 23 isolated from the red mangrove (Rhizophora
      mangle) rhizosphere produced a highly active compound against the microalga
      Chlorella vulgaris, often used to assess the phytotoxic activity. As a result,
      the bioassay-guided fractionation led to the isolation of the mixture of the
      known compounds bafilomycin B1 and bafilomycin B2. The chemical structures of
      bafilomycin B1 and bafilomycin B2 were established based on their spectroscopic
      data by infrared (IR), mass spectrometry (MS), (1)H nuclear magnetic resonance
      (NMR), gradient-enhanced heteronuclear multiple quantum coherence (gHMQC), and
      gradient-enhanced heteronuclear multiple-bond connectivity (gHMBC) as well as
      comparison with reference data from the literature. Moreover, it was also
      possible to identify other bafilomycins using non-chromatographic-dependent
      techniques (Tandem mass spectrometry). Additionally, this is the first report on
      the phytotoxic activity of bafilomycin B1. 

PMID- 23979947
TI  - The predictive value of circulating anti-Mullerian hormone in women with
      polycystic ovarian syndrome receiving clomiphene citrate: a prospective
      observational study.
AB  - CONTEXT: Elevated serum anti-Mullerian hormone (AMH) concentration in women with
      polycystic ovarian syndrome (PCOS) is known to lower sensitivity of ovarian
      follicles to circulating FSH. This effect may compromise the outcome of
      clomiphene citrate (CC) ovulation induction. OBJECTIVE: The objective of the
      study was to investigate the impact of high circulating AMH on the outcome of CC
      ovulation induction in women with PCOS. DESIGN: This was a prospective cohort
      observational study. SETTING: The study was conducted at the Fertility Unit,
      Derby, United Kingdom. PATIENTS: Sixty anovulatory women with PCOS participated
      in the study. INTERVENTIONS: Serum AMH concentrations were measured on cycle day
      2 during 187 CC cycles. These concentrations were compared between responders and
      nonresponders. The receiver-operating characteristic curve was used to evaluate
      the prognostic value of circulating AMH. The success rates of CC were compared
      between patients with high vs low AMH levels. The dose of CC required to achieve
      ovulation was correlated with serum AMH concentrations. MAIN OUTCOME MEASURES:
      Ovulation and pregnancy rates were measured. RESULTS: Serum AMH concentrations
      were significantly (P < .001) lower in responders (achieving ovulation) vs
      nonresponders (mean +/- SEM, 2.5 +/- 0.1 vs 5.8 +/- 0.7 ng/mL, respectively).
      Similarly, serum AMH concentrations were significantly (P = .046) lower in
      pregnant (3.0 +/- 0.4 ng/mL) vs nonpregnant patients (4.4 +/- 0.5 ng/mL). There
      was a significant (P = .02) gradient increase of serum AMH levels with the
      increasing dose of CC required to achieve ovulation. The receiver-operating
      characteristic curve showed AMH to be a useful predictor of no ovulation (area
      under the curve, 0.809; P < .001) with a useful cutoff level of 3.4 ng/mL.
      Ovulation and pregnancy rates were significantly higher (97%, P < .001, and 46%,
      P = .034) in patients with low AMH (<3.4 ng/mL) vs women with AMH 3.4 ng/mL or
      greater (48% and 19%). CONCLUSION: PCOS women with high circulating AMH (>= 3.4
      ng/mL) seem to be resistant to CC and may require a higher starting dose.

PMID- 23979948
TI  - Early development of hyperparathyroidism due to loss of PTH transcriptional
      repression in patients with HNF1beta mutations?
AB  - CONTEXT: Heterozygous mutations or deletions of the transcription factor
      hepatocyte nuclear factor 1beta (HNF1beta) result in a heterogeneous syndrome
      characterized by renal cysts and diabetes, together with a variety of other
      extrarenal and renal manifestations. Interestingly, in several patients with
      HNF1beta abnormalities, we observed early hyperparathyroidism and PTH levels that
      we judged inappropriately high compared with the degree of renal function
      decline. OBJECTIVE: Based on the above clinical observations, we tested the
      hypothesis of a direct role of HNF1beta in the transcriptional regulation of the
      human PTH gene in the parathyroid gland. DESIGN, SETTING, AND PATIENTS:
      Immunostaining of human parathyroid sections, RT-PCR, chromatin
      immunoprecipitation (ChIP), and luciferase reporter assays in human embryonic
      kidney cells (HEK293) were performed. We eventually report clinical data from all
      11 HNF1beta patients known at our institute, 9 with heterozygous HNF1beta whole
      gene deletions and 2 with heterozygous HNF1beta mutations. RESULTS: PTH levels
      were high in 8 patients. In 2 of these patients, the hyperparathyroidism was
      clearly appropriate for the level of kidney function, whereas PTH might be
      discrepant in the others. We demonstrated HNF1beta expression in PTH-positive
      cells of human parathyroid gland. Chromatin immunoprecipitation analysis showed
      that HNF1beta directly binds responsive elements within the human PTH promoter.
      Cotransfection of a PTH promoter- luciferase construct with a wild-type HNF1beta
      construct resulted in a maximal reduction of 30% of PTH promoter activity.
      Importantly, HNF1beta mutants lacked this inhibitory property. Serial deletions
      in the PTH promoter construct revealed that the inhibitory effect of HNF1beta
      resides between -200 and -70 bp from the transcription initiation site.
      CONCLUSIONS: Our data demonstrate that HNF1beta is a novel repressor of human PTH
      gene transcription, which could contribute to the development of
      hyperparathyroidism in patients with HNF1beta mutations or deletions.

PMID- 23979949
TI  - Circadian clock characteristics are altered in human thyroid malignant nodules.
AB  - CONTEXT: The circadian clock represents the body's molecular time-keeping system.
      Recent findings revealed strong changes of clock gene expression in various types
      of human cancers. OBJECTIVE: Due to emerging evidence on the connection between
      the circadian oscillator, cell cycle, and oncogenic transformation, we aimed to
      characterize the circadian clockwork in human benign and malignant thyroid
      nodules. DESIGN: Clock transcript levels were assessed by quantitative RT-PCR in
      thyroid tissues. To provide molecular characteristics of human thyroid clockwork,
      primary thyrocytes established from normal or nodular thyroid tissue biopsies
      were subjected to in vitro synchronization with subsequent clock gene expression
      analysis by circadian bioluminescence reporter assay and by quantitative RT-PCR.
      RESULTS: The expression levels of the Bmal1 were up-regulated in tissue samples
      of follicular thyroid carcinoma (FTC), and in papillary thyroid carcinoma (PTC),
      as compared with normal thyroid and benign nodules, whereas Cry2 was down
      regulated in FTC and PTC. Human thyrocytes derived from normal thyroid tissue
      exhibited high-amplitude circadian oscillations of Bmal1-luciferase reporter
      expression and endogenous clock transcripts. Thyrocytes established from FTC and
      PTC exhibited clock transcript oscillations similar to those of normal thyroid
      tissue and benign nodules (except for Per2 altered in PTC), whereas cells derived
      from poorly differentiated thyroid carcinoma exhibited altered circadian
      oscillations. CONCLUSIONS: This is the first study demonstrating a molecular
      makeup of the human thyroid circadian clock. Characterization of the thyroid
      clock machinery alterations upon thyroid nodule malignant transformation
      contributes to understanding the connections between circadian clocks and
      oncogenic transformation. Moreover, it might help in improving the thyroid nodule
      preoperative diagnostics.

PMID- 23979950
TI  - Cognitive development in congenital hypothyroidism: is overtreatment a greater
      threat than undertreatment?
AB  - BACKGROUND: Optimal treatment of children with congenital hypothyroidism (CHT) is
      still debated. Our objective was to evaluate whether early undertreatment (UT)
      and overtreatment (OT) influence cognitive development at age 11 years. METHODS:
      Sixty-one patients (27 severe CHT, 34 mild CHT) were psychologically tested at
      ages 1.8 (Mental Development Index), 6 [intelligence quotient (IQ) 6], and 11
      years (IQ11). Scores for cognitive development were related to initial levels of
      TSH normalization (fast, moderate, or slow) and to total durations of the UT and
      OT episodes within the first 2 years of life (no, short, or long UT/OT). UT and
      OT were defined as a free T4 (fT4) concentration below or above the individual
      fT4 steady-state concentration range (+/-2 SD). RESULTS: Patients with fast and
      moderate TSH normalization had higher Mental Development Index scores than
      patients with slow TSH normalization; 14.2 and 7.7 points higher, respectively (P
      = .001). TSH normalization had no significant effect on IQ11. Patients with long
      and short overtreatment had IQ11s that were -17.8 and -13.4 points lower,
      respectively, than the IQ11s of patients with no overtreatment (P = .014). UT
      without OT was associated with normal development scores, but UT with OT was
      associated with -14.7 points lower IQ11s than UT without OT (P = .005).
      CONCLUSIONS: Our study suggests that CHT overtreatment during the first 2 years
      leads to lowered cognitive outcomes at 11 years, whereas undertreatment, if not
      complicated by overtreatment, results in a normal cognitive development. Fast TSH
      normalization at initial treatment leads to above-normal development scores at a
      young age but does not affect IQ at age 11 years.

PMID- 23979951
TI  - Does inflammation determine metabolic health status in obese and nonobese adults?
AB  - CONTEXT: Inflammation is a potential mechanism linking obesity and
      cardiometabolic risk. Limited data on inflammatory markers in metabolically
      healthy obese and nonobese individuals exist. OBJECTIVE: The aim of the study was
      to investigate the extent to which differences between metabolically healthy and
      unhealthy obese and nonobese adults, defined using a range of metabolic health
      definitions, are correlated with a range of inflammatory markers. DESIGN: A cross
      sectional sample of 2047 men and women aged 45-74 years participated in the
      study. Participants were classified as obese (body mass index >= 30 kg/m(2)) and
      nonobese (body mass index < 30 kg/m(2)). Metabolic health status was defined
      using 5 existing metabolic health definitions based on a range of cardiometabolic
      abnormalities. Serum acute-phase reactants, adipocytokines, proinflammatory
      cytokines, and white blood cell counts were determined. RESULTS: According to
      most definitions, metabolically healthy obese and nonobese individuals presented
      with lower concentrations of complement component 3, C-reactive protein, TNF
      alpha, IL-6, and plasminogen activator inhibitor-1; higher adiponectin levels;
      and reduced white blood cell count compared to their metabolically unhealthy
      counterparts. Logistic regression analysis identified greater likelihood of
      metabolically healthy obesity among individuals with lower levels of complement
      component 3 (odds ratios [ORs], 2-3.5), IL-6 (ORs, 1.7-2.9), plasminogen
      activator inhibitor-1 (ORs, 1.7-2.9), and white blood cells (ORs, 2.1-2.5) and
      higher adiponectin concentrations (ORs, 2.6-4.0). CONCLUSIONS: Favorable
      inflammatory status is positively associated with metabolic health in obese and
      nonobese individuals. These findings are of public health and clinical
      significance in terms of screening and stratification based on metabolic health
      phenotype to identify those at greatest cardiometabolic risk for whom appropriate
      therapeutic or intervention strategies should be developed.

PMID- 23979952
TI  - A case of fetal goiter that resolved spontaneously after birth.

PMID- 23979953
TI  - Calcitriol-mediated hypercalcemia: causes and course in 101 patients.
AB  - CONTEXT: Hypercalcemia mediated by 1,25-dihydroxy vitamin D (calcitriol) is
      uncommon, with evidence on etiology limited to small case series or case reports.
      OBJECTIVE: The objective of the study was to systematically identify a large
      series of cases of calcitriol-mediated hypercalcemia and document the
      presentation, demographics, and clinical course across etiologies. DESIGN,
      SETTING, AND PATIENTS: The study was a hospital-based, retrospective case series,
      identifying subjects from 1999 through 2009 across the public hospital system in
      Queensland, Australia. All patients aged over 18 years were identified that had
      persistent hypercalcemia associated with elevated or inappropriately normal
      calcitriol concentration or elevated serum angiotensin-converting enzyme.
      RESULTS: A total of 101 cases were identified. Sarcoidosis was the most common
      etiology (49%), followed by hematological malignancy (17%) and infections (8%).
      Etiologies not previously described include squamous cell carcinoma of the
      tongue, ovarian cystadenocarcinoma, and chronic lymphocytic leukemia. Median
      serum angiotensin-converting enzyme was higher in sarcoid patients compared with
      all other causes [218 U/L (176-277) vs 155 U/L (110-208), P < .001], but a level
      above the normal range did not discriminate well between cases of sarcoidosis and
      other causes (specificity at cutoff of 130 U/L was only 31%). However, a value
      greater than 250 U/L was highly specific (89%) for sarcoidosis but lacked
      sensitivity (31%). A calcitriol level greater than 300 pmol/L was not seen in
      sarcoidosis but was seen with other etiologies. Cases with neoplastic etiologies
      were older (61.4 +/- 11.4 y) than all other subjects (51.7 +/- 15.0 y, P = .006).
      CONCLUSIONS: Hypercalcemia mediated by calcitriol remains a rare presentation. In
      almost half the cases, sarcoidosis was the underlying cause, whereas a third of
      patients had cancer or systemic infections.

PMID- 23979954
TI  - Lifestyle and metformin treatment favorably influence lipoprotein subfraction
      distribution in the Diabetes Prevention Program.
AB  - CONTEXT: Although intensive lifestyle change (ILS) and metformin reduce diabetes
      incidence in subjects with impaired glucose tolerance (IGT), their effects on
      lipoprotein subfractions have not been studied. OBJECTIVE: The objective of the
      study was to characterize the effects of ILS and metformin vs placebo
      interventions on lipoprotein subfractions in the Diabetes Prevention Program.
      DESIGN: This was a randomized clinical trial, testing the effects of ILS,
      metformin, and placebo on diabetes development in subjects with IGT.
      PARTICIPANTS: Selected individuals with IGT randomized in the Diabetes Prevention
      Program participated in the study. INTERVENTIONS: Interventions included
      randomization to metformin 850 mg or placebo twice daily or ILS aimed at a 7%
      weight loss using a low-fat diet with increased physical activity. MAIN OUTCOME
      MEASURES: Lipoprotein subfraction size, density, and concentration measured by
      magnetic resonance and density gradient ultracentrifugation at baseline and 1
      year were measured. RESULTS: ILS decreased large and buoyant very low-density
      lipoprotein, small and dense low-density lipoprotein (LDL), and small high
      density lipoprotein (HDL) and raised large HDL. Metformin modestly reduced small
      and dense LDL and raised small and large HDL. Change in insulin resistance
      largely accounted for the intervention-associated decreases in large very low
      density lipoprotein, whereas changes in body mass index (BMI) and adiponectin
      were strongly associated with changes in LDL. Baseline and a change in
      adiponectin were related to change in large HDL, and BMI change associated with
      small HDL change. The effect of metformin to increase small HDL was independent
      of adiponectin, BMI, and insulin resistance. CONCLUSION: ILS and metformin
      treatment have favorable effects on lipoprotein subfractions that are primarily
      mediated by intervention-related changes in insulin resistance, BMI, and
      adiponectin. Interventions that slow the development of diabetes may also retard
      the progression of atherosclerosis.

PMID- 23979956
TI  - PGE2 and PGF2alpha concentrations in human endometrial fluid as biomarkers for
      embryonic implantation.
AB  - BACKGROUND: Prostaglandin (PG) signaling has been implicated in embryonic
      implantation in several animal species including humans; however, this knowledge
      has not yet been clinically translated. The objective of this work is to
      investigate whether PGE2 and PGF2alpha in endometrial fluid (EF) can be used as
      biomarkers of human embryonic implantation. PATIENTS AND METHODS: Lipidomic
      profile of human EF (n = 173) obtained through natural cycles, hormonal
      replacement therapy, controlled ovarian stimulation, and refractory endometrium
      induced by the insertion of an intrauterine device was analyzed by liquid
      chromatography and tandem mass spectrometry. Immunohistochemistry, Western
      blotting, immunolocalization of PG receptors on mouse embryos, embryo adhesion
      assay, pharmacological interventions, and statistical analysis were conducted.
      RESULTS: PGE2 and PGF2alpha concentrations increased significantly in the human
      EF during the window of implantation in natural cycles and assisted reproductive
      technologies patients undergoing in vitro fertilization and ovum donation. This
      profile was abrogated in the refractory endometrium. We also demonstrated that
      PGE2 and PGF2alpha synthases are located in the endometrial epithelium being
      hormonally regulated during the window of implantation, and PG receptors are
      expressed in the trophoectoderm and inner cell mass of mouse blastocysts. Using
      an in vitro model of embryo adhesion, we demonstrated that inhibition of PGE2 and
      PGF2alpha or PG receptors (EP2 and FP) prevents embryo adhesion, which can be
      overcome by adding these molecules back or using their agonists. Finally, in a
      pilot study, we demonstrated that PGE2 and PGF2alpha levels from EF 24 hours
      prior to embryo transfer could predict pregnancy outcome. CONCLUSIONS: Our
      results suggest that PGE2 and PGF2alpha concentrations 24 hours prior to embryo
      transfer are potential noninvasive biomarkers of endometrial receptivity.

PMID- 23979955
TI  - The effect of three or six years of denosumab exposure in women with
      postmenopausal osteoporosis: results from the FREEDOM extension.
AB  - CONTEXT: The Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6
      Months (FREEDOM) extension is evaluating the long-term efficacy and safety of
      denosumab for up to 10 years. OBJECTIVE: The objective of the study was to report
      results from the first 3 years of the extension, representing up to 6 years of
      denosumab exposure. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter,
      international, open-label study of 4550 women. INTERVENTION: Women from the
      FREEDOM denosumab group received 3 more years of denosumab for a total of 6 years
      (long-term) and women from the FREEDOM placebo group received 3 years of
      denosumab (crossover). MAIN OUTCOME MEASURES: Bone turnover markers (BTMs), bone
      mineral density (BMD), fracture, and safety data are reported. RESULTS:
      Reductions in BTMs were maintained (long-term) or achieved rapidly (crossover)
      after denosumab administration. In the long-term group, BMD further increased for
      cumulative 6-year gains of 15.2% (lumbar spine) and 7.5% (total hip). During the
      first 3 years of denosumab treatment, the crossover group had significant gains
      in lumbar spine (9.4%) and total hip (4.8%) BMD, similar to the long-term group
      during the 3-year FREEDOM trial. In the long-term group, fracture incidences
      remained low and below the rates projected for a virtual placebo cohort. In the
      crossover group, 3-year incidences of new vertebral and nonvertebral fractures
      were similar to those of the FREEDOM denosumab group. Incidence rates of adverse
      events did not increase over time. Six participants had events of osteonecrosis
      of the jaw confirmed by adjudication. One participant had a fracture adjudicated
      as consistent with atypical femoral fracture. CONCLUSION: Denosumab treatment for
      6 years remained well tolerated, maintained reduced bone turnover, and continued
      to increase BMD. Fracture incidence remained low.

PMID- 23979957
TI  - Association between vitamin D metabolism gene polymorphisms and risk of islet
      autoimmunity and progression to type 1 diabetes: the diabetes autoimmunity study
      in the young (DAISY).
AB  - CONTEXT: Vitamin D metabolism genes have been associated with type 1 diabetes
      (T1D) risk; however, these genes have not been investigated for association with
      the preclinical phase of T1D, islet autoimmunity (IA). Studies of vitamin D
      metabolism genes may elucidate the role of vitamin D in complex diseases.
      OBJECTIVE: The objective of the study was to explore the association between
      seven vitamin D metabolism gene single-nucleotide polymorphisms (SNPs) and the
      risk of IA and progression to T1D. DESIGN: The Diabetes Autoimmunity Study in the
      Young is a longitudinal, observational study. SETTING: Newborn screening for
      human leukocyte antigen, sibling and offspring recruitment, and follow-up took
      place in Denver, Colorado. PARTICIPANTS: A total of 1708 children at increased
      genetic risk of T1D participated in the study: 148 developed IA and 62 IA
      positive children progressed to T1D. MAIN OUTCOME MEASURES: IA, defined as
      positivity for glutamic acid decarboxylase, insulin, or IA-2 autoantibodies on
      two or more consecutive visits, and T1D, diagnosed by a physician, were the main
      outcome measures. RESULTS: The risk of IA was associated with DHCR7/NADSYN1
      rs12785878 and CYP27B1 rs4646536 [hazard ratio 1.36, 95% confidence interval 1.08
      1.73 (for each additional minor allele) and hazard ratio 0.59, 95% confidence
      interval 0.39-0.89 (for A/G compared with the A/A genotype), respectively]. None
      of the vitamin D SNPs typed was associated with progression to T1D in IA-positive
      children. Six of the seven SNPs were significantly associated with 25
      hydroxyvitamin D levels. CONCLUSIONS: DHCR7/NADSYN1 rs12785878 and CYP27B1
      rs4646536 may play an important role in islet autoimmunity, the preclinical phase
      of T1D. These findings should be replicated in larger cohorts for confirmation.

PMID- 23979958
TI  - Molecular screening for a personalized treatment approach in advanced
      adrenocortical cancer.
AB  - CONTEXT: Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and
      scant treatment options. In ACC, no personalized approach has emerged but no
      extensive molecular screening has been performed to date. OBJECTIVE: The
      objective of the study was to evaluate the presence of a large number of
      potentially targetable molecular events in a large cohort of advanced ACC.
      DESIGN, SETTING, AND PARTICIPANTS: We used hot spot gene sequencing (Ion Torrent,
      40 patients) and comparative genomic hybridization (CGH; 28 patients; a subset of
      the entire cohort) in adult stage III-IV ACC samples to screen for mutations and
      copy number abnormalities of potential interest for therapeutic use in 46 and 130
      genes, respectively. RESULTS: At least one copy number alteration or mutation was
      found in 19 patients (47.5%). The most frequent mutations were detected on TP53,
      ATM, and CTNNB1 [6 of 40 (15%), 5 of 40 (12.5%), and 4 of 40 (10%),
      respectively]. The most frequent copy number alterations identified were:
      amplification of the CDK4 oncogene (5 of 28; 17.9%) and deletion of the CDKN2A (4
      of 28; 14.3%) and CDKN2B (3 of 28; 10.7%) tumor suppressor genes. Amplifications
      of FGFR1, FGF9, or FRS2 were discovered in three subjects (10.7%). Associated
      alterations were: deletions of CDKN2A, CDKN2B with ATM mutations, and TP53
      mutations with CTNNB1 mutations. CONCLUSIONS: No simple targetable molecular
      event emerged. Drugs targeting the cell cycle could be the most relevant new
      therapeutic approach for patients with advanced ACC. Inhibitors of the fibroblast
      growth factor receptor pathway could also be a therapeutic option in a subset of
      patients, whereas other targeted therapies should be considered on a case-by-case
      basis.

PMID- 23979961
TI  - 1H, 13C and 15N NMR assignments of a mutant of UV inducible transcript (S55A
      UVI31+) from Chlamydomonas reinhardtii.
AB  - Almost complete sequence specific (1)H, (13)C and (15)N resonance assignments of
      a mutant of UV inducible transcript (S55A-UVI31+) from Chlamydomonas reinhardtii
      are reported, as a prelude to its structural and functional characterization.
      Site-directed mutagenesis of uvi31+ was carried out using complementary mutation
      harbouring oligonucleotides for S55A mutant. The resulting mutant was sequenced
      and then S55A mutant of uvi31+ cDNA were expressed in E. coli, and purification
      were carried out from where the protein was purified to high homogeneity. The
      point mutation S55A in UVI31+ results in a significant enhancement in its DNA
      endonuclease activity as compared to its wild type protein. 

PMID- 23979959
TI  - Targeted next-generation sequencing panel (ThyroSeq) for detection of mutations
      in thyroid cancer.
AB  - OBJECTIVES: Next-generation sequencing (NGS) allows for high-throughput
      sequencing analysis of large regions of the human genome. We explored the use of
      targeted NGS for simultaneous testing for multiple mutations in thyroid cancer.
      DESIGN: A custom panel (ThyroSeq) was designed to target 12 cancer genes with 284
      mutational hot spots. Sequencing was performed to analyze DNA from 228 thyroid
      neoplastic and nonneoplastic samples including 105 frozen, 72 formalin-fixed, and
      51 fine-needle aspiration samples representing all major types of thyroid cancer.
      RESULTS: Only 5-10 ng of input DNA was sufficient for successful analysis of
      99.6% of samples. The analytical accuracy for mutation detection was 100% with
      the sensitivity of 3%-5% of mutant allele. ThyroSeq DNA assay identified
      mutations in 19 of 27 of classic papillary thyroid carcinomas (PTCs) (70%), 25 of
      30 follicular variant PTCs (83%), 14 of 18 conventional (78%) and 7 of 18
      oncocytic follicular carcinomas (39%), 3 of 10 poorly differentiated carcinomas
      (30%), 20 of 27 anaplastic (ATCs) (74%), and 11 of 15 medullary thyroid
      carcinomas (73%). In contrast, 5 of 83 benign nodules (6%) were positive for
      mutations. Most tumors had a single mutation, whereas several ATCs and PTCs
      demonstrated two or three mutations. The most common mutations detected were BRAF
      and RAS followed by PIK3CA, TP53, TSHR, PTEN, GNAS, CTNNB1, and RET. The BRAF
      mutant allele frequency was 18%-48% in PTCs and was lower in ATCs. CONCLUSIONS:
      The ThyroSeq NGS panel allows simultaneous testing for multiple mutations with
      high accuracy and sensitivity, requires a small amount of DNA and can be
      performed in a variety of thyroid tissue and fine-needle aspiration samples, and
      provides quantitative assessment of mutant alleles. Using this approach, the
      point mutations were detected in 30%-83% of specific types of thyroid cancer and
      in only 6% of benign thyroid nodules and were shown to be present in the majority
      of cells within the cancer nodule.

PMID- 23979962
TI  - Activation of the aryl hydrocarbon receptor by a component of cigarette smoke
      reduces germ cell proliferation in the human fetal ovary.
AB  - Fetal life is a critical time for female fertility, when germ cells complete
      proliferation, initiate meiosis and ultimately form the lifetime stock of
      primordial follicles. Female fertility may be reduced by in utero exposure to
      cigarette smoke, which contains ligands for the aryl hydrocarbon receptor (AhR).
      The AhR is a critical regulator of ovarian germ cell survival in mice; thus
      activation of this receptor in the ovaries of fetuses exposed to maternal
      cigarette smoke in utero may provide a mechanism by which female fertility is
      reduced in later life. We have therefore investigated AhR expression in the human
      fetal ovary, and examined the effects of an AhR ligand present in cigarette
      smoke, on germ cells in human fetal ovaries cultured in vitro. The results showed
      that AHR mRNA expression increased 2-fold between first and late second trimester
      (P = 0.008). AhR protein was confined to germ cells at all gestations, but varied
      from expression in most germ cells during the first trimester, to only patchy
      expression by clusters of germ cells at later gestations. Culture of human fetal
      ovaries with the AhR ligand 9,10-dimethyl-1,2-benzanthracene-3,4-dihydrodiol
      (DMBA-DHD; a component of cigarette smoke) did not affect germ cell number in
      vitro, but significantly reduced the proportion of proliferating germ cells by
      29% (as assessed by phospho-histone H3 staining (P = 0.04)). Germ cell apoptosis
      was not significantly affected. These results reveal that germ cells in the human
      fetal ovary express AhR from the proliferative stage of development through entry
      into meiosis and beyond, and demonstrate that AhR ligands found in cigarette
      smoke have the capacity to impair human fetal ovarian germ cell proliferation. 

PMID- 23979963
TI  - The road not taken: transferability issues in multinational trials.
AB  - BACKGROUND: National regulatory agencies often have to use cost-effectiveness
      (CE) data from multinational randomized controlled trials (RCTs) for national
      decision making on reimbursement of new drugs. We need to make the best use of
      these patient-level data to obtain estimates of country-specific CE. Several
      methods, ranging from simple to statistically complex, have existed for years. We
      investigated which of these methods are used to estimate CE ratios in economic
      evaluations performed alongside recent, multinational RCTs that enrolled at least
      500 patients. METHODS: In this systematic literature review, studies were
      classified based on whether resource use, unit costs, health outcomes and utility
      value sets were obtained from all countries, a subset of countries or one
      country. We recorded if the study presented trial-wide and country-specific CE
      results and reported the statistical analyses that were used to estimate them.
      RESULTS: We included 21 studies, of which the majority used measurements of
      health care utilization and health outcomes from all countries to estimate CE.
      Thirteen studies used a one-country valuation of health care utilization; six
      used a multi-country valuation. Despite the availability of country-specific
      utility value sets, none of the studies that presented quality-adjusted life
      years (QALYs) used multi-country valuation. Valuation of health care utilization
      and health outcomes was not always consistent within a study: three studies
      combined a multi-country valuation of health care utilization, with a one-country
      valuation of health outcomes. Most studies calculated trial-wide CE estimates,
      while 11 studies calculated country- or region-specific estimates. Thirteen
      studies used relatively simple methods, which do not take the possible
      interaction between the country and treatment effect on health care utilization
      and health outcomes into account. Eight studies used more advanced statistical
      methods. Three of them used a fixed-effects modeling approach. Five studies
      explicitly took the hierarchical structure of the data into account, which leads
      to more appropriate estimates of population average results and associated
      standard errors. In this way, they help improve transferability of the published
      results. CONCLUSION: Based on this systematic review, we concluded that the
      uptake of more advanced statistical methods has been relatively slow, while
      simpler naive methods are still routinely employed.

PMID- 23979964
TI  - Is a 40 % absorption of iron from a ferrous ascorbate reference dose appropriate
      to assess iron absorption independent of iron status?
AB  - Although a 40 % absorption of a standard reference dose corresponds to iron (Fe)
      absorption in borderline Fe-deficient subjects, this percentage is currently
      applied to all subjects independent of Fe status: (a) to assess the use of the 40
      % of Fe absorption of the reference dose (FeRD%) for subjects with iron-depleted
      stores (IDS), normal Fe status (NIS), Fe deficiency without anemia (IDWA), and Fe
      deficiency anemia (IDA) and (b) to explore relationships between Fe status
      biomarkers and FeRD%. Six hundred forty-six participants (582 women and 64 men)
      were selected from multiple Fe bioavailability studies and classified into four
      groups based on Fe status: NIS, IDS, IDWA, and IDA. All men were classified as
      normal. The absorption from FeRD% was calculated in each group and correlated
      with Fe status biomarkers. (a) Women with IDS absorbed 40 (18.9-84.7) % of the
      reference dose; (b) for male subjects with NIS, the absorption of the reference
      dose was 19 (9.8-36.1) %, while for females, absorption was observed as to be 34
      (16.7-68.6)%. In the case of subjects with IDWA, a 43 (19.7-92.5) % absorption
      was observed, while subjects with IDA demonstrated 67 (45.2-98.6) % absorption.
      Serum ferritin (SF) had the strongest inverse correlation with FeRD% (r = -0.41,
      p < 0.001). A transferrin saturation (TS) <15 % increases the probability that
      the FeRD% will be highly elevated (OR, 5.05; 95 % CI, 2.73, 9.31; p < 0.001). A
      40 % absorption as reference dose is only appropriate to assess Fe absorption in
      subjects with IDS and IDWA. SF had an inverse correlation with FeRD%, and TS
      increases the probability that the FeRD% will be elevated by over fivefold. 

PMID- 23979965
TI  - Phase IIb multicentred randomised trial of besifovir (LB80380) versus entecavir
      in Asian patients with chronic hepatitis B.
AB  - BACKGROUND: Besifovir (LB80380) is an acyclic nucleotide phosphonate effective in
      hepatitis B virus (HBV) DNA suppression for both treatment-naive and lamivudine
      resistant chronic hepatitis B (CHB) patients in preliminary studies. DESIGN: We
      aimed to compare the safety and antiviral activity of two doses of besifovir (90
      mg and 150 mg daily) with entecavir 0.5 mg daily in CHB patients. 114 patients
      were randomised to receive besifovir 90 mg daily (n=36), besifovir 150 mg daily
      (n=39) or entecavir 0.5 mg daily (n=39). HBV DNA and liver biochemistry,
      including serum L-carnitine levels, were monitored. RESULTS: At week 48, in the
      intention-to-treat population, the proportion of patients achieving undetectable
      HBV DNA (<20 IU/mL) were 63.6%, 62.9% and 58.3%, respectively (p>0.05). The serum
      mean log10 HBV DNA changes from baseline for the HBeAg-positive patients were 
      5.84, -5.91 and -6.18, respectively; and for the HBeAg-negative patients were 
      4.65, -4.55 and -4.67, respectively (p>0.05). There were no differences in the
      proportions of patients achieving normalisation of alanine aminotransferase
      (91.7%, 76.9%, 89.7%, respectively) and HBeAg seroconversion (11.11%, 15%, 9.52%,
      respectively) among all three groups. None of the patients had resistant
      mutations or increase in serum creatinine of >0.5 mg/dL from baseline. 64 (94.1%)
      patients on besifovir had lowering of serum L-carnitine (not tested in entecavir
      patients). L-carnitine levels returned to normal with carnitine supplement.
      CONCLUSIONS: At 48 weeks, 90 mg and 150 mg daily of besifovir were non-inferior
      to entecavir 0.5 mg daily in treatment-naive CHB patients. The only significant
      side effect of besifovir was L-carnitine depletion, requiring carnitine
      supplementation.

PMID- 23979967
TI  - Limitation of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography (FDG
      PET) to detect early synchronous primary cancers in patients with untreated head
      and neck squamous cell cancer.
AB  - OBJECTIVE: Patients with head and neck squamous cell carcinoma (HNSCC) often
      develop synchronous multiple primary cancers. It is important to detect second
      primary cancer in HNSCC patients, because it influences treatment selection of
      primary cancer. The aim of this study was to evaluate the utility of 2-deoxy-2-[F
      18]fluoro-D-glucose (FDG)-positron emission tomography (PET) for detecting
      synchronous primary cancers at the initial staging of patients with HNSCC.
      METHODS: Three hundred and forty-seven patients with untreated HNSCC underwent
      FDG-PET with or without computed tomography fusion and other routine workups,
      including upper gastrointestinal Lugol chromoendoscopy, for the initial staging.
      We examined the prevalence of second primary cancer in these patients and the
      utility of PET. RESULTS: We identified 57 synchronous primary cancers in 53
      patients, of which only 33 % were detected with PET. The most common site for the
      second primary cancer was the esophagus (49 %), followed by stomach (14 %) and
      head and neck (11 %). Most early-stage esophageal cancers and stomach cancers
      were detected using Lugol chromoendoscopy but not PET. CONCLUSION: Although PET
      is useful for detecting synchronous primary cancers, it is not a sensitive
      technique for detecting early esophageal cancers and gastric cancers. Therefore,
      Lugol chromoendoscopy is indispensable for detecting synchronous upper
      gastrointestinal cancers in HNSCC patients.

PMID- 23979966
TI  - The effect of short-term vitamin E against radioiodine-induced early lacrimal
      gland damage.
AB  - Radioiodine (RAI) is a well-known radionuclide which is used in vivo both for
      diagnostic and therapeutic purposes, particularly for the treatment of
      hyperthyroidism and thyroid cancer. Vitamin E is a well-known antioxidant
      vitamin. The aim of this study was to evaluate whether there was a protective
      effect of short-term vitamin E on RAI-induced lacrimal gland early damage in
      experimental animal models. METHODS: Twentyfour rats were randomly divided into
      two groups. The first group (RAI group) was administreted 3 mCi (131)I by gastric
      gavage and 1 mL physiological saline intraperitoneally. The second group (RAI +
      Vitamin E) was administrated 3 mCi (131)I by gastric gavage and 1 mL vitamin E
      intraperitoneally. After 24 h of the last dose being administered on the 7th day,
      the animals were decapitated. The lacrimal glands [Intraorbital (IG),
      extraorbital (EG) and harderian glands (HG)] of the rats were removed for
      histopathological examination. RESULTS: Periductal and/or periacinar fibrosis in
      all lacrimal glands were observed to be statistically significantly less frequent
      in the RAI + Vitamin E group compared to the RAI group. The existence of the
      abnormal lobular pattern and peripheral basophilia and irregular nucleus shape in
      IG and in EG, the poorly defined acidophilic cell outline and periductal
      infiltration in IG and in HG were observed to be statistically significantly less
      frequent in the RAI + Vitamin E group than in the RAI group. CONCLUSION:
      According to study results, histopathological examinations revealed that vitamin
      E protects rat lacrimal glands against RAI-related early damage.

PMID- 23979968
TI  - Treatment of medial tibial stress syndrome: a systematic review.
AB  - BACKGROUND: Medial tibial stress syndrome (MTSS) is a common exercise-induced leg
      injury among athletes and military personnel. Several treatment options have been
      described in the literature, but it remains unclear which treatment is most
      effective. OBJECTIVE: The objective of this systematic review was to assess the
      effectiveness of any intervention in the treatment of MTSS. STUDY SELECTION:
      Published or non-published studies, reporting randomized or non-randomized
      controlled trials of any treatment in subjects with MTSS were eligible for
      inclusion. Treatments were assessed for effects on pain, time to recovery or
      global perceived effect. DATA SOURCES: Computerized bibliographic databases
      (MEDLINE, CENTRAL, EMBASE, CINAHL, PEDro and SPORTDiscus) and trial registries
      were searched for relevant reports, from their inception to 1 June 2012. Grey
      literature was searched for additional relevant reports. STUDY APPRAISAL: The
      Cochrane Risk of Bias Tool was used to appraise study quality of randomized
      clinical trials (RCTs) whereas the Newcastle Ottawa Scale was used to appraise
      non-randomized trials. The 'levels of evidence', according to the Oxford Centre
      for Evidence-Based Medicine, addressed the impact of the assessed trials. Two
      reviewers independently performed the search for articles, study selection, data
      extraction and appraised methodological quality. RESULTS: Eleven trials were
      included in this systematic review. All RCTs revealed a high risk of bias (Level
      3 of evidence). Both non-randomized clinical trials were found to be of poor
      quality (Level 4 of evidence). RCTs, studying the effect of a lower leg brace
      versus no lower leg brace, and iontophoresis versus phonophoresis, were pooled
      using a fixed-effects model. No significant differences were found for lower leg
      braces (standardized mean difference [SMD] -0.06; 95 % CI -0.44 to 0.32, p =
      0.76), or iontophoresis (SMD 0.09; 95 % CI -0.50 to 0.68, p = 0.76).
      Iontophoresis, phonophoresis, ice massage, ultrasound therapy, periosteal pecking
      and extracorporeal shockwave therapy (ESWT) could be effective in treating MTSS
      when compared with control (Level 3 to 4 of evidence). Low-energy laser
      treatment, stretching and strengthening exercises, sports compression stockings,
      lower leg braces and pulsed electromagnetic fields have not been proven to be
      effective in treating MTSS (level 3 of evidence). CONCLUSION: None of the studies
      are sufficiently free from methodological bias to recommend any of the treatments
      investigated. Of those examined, ESWT appears to have the most promise.

PMID- 23979969
TI  - Gibberellin 3-oxidase gene expression patterns influence gibberellin
      biosynthesis, growth, and development in pea.
AB  - Gibberellins (GAs) are key modulators of plant growth and development. PsGA3ox1
      (LE) encodes a GA 3beta-hydroxylase that catalyzes the conversion of GA20 to
      biologically active GA1. To further clarify the role of GA3ox expression during
      pea (Pisum sativum) plant growth and development, we generated transgenic pea
      lines (in a lele background) with cauliflower mosaic virus-35S-driven expression
      of PsGA3ox1 (LE). PsGA3ox1 transgene expression led to higher GA1 concentrations
      in a tissue-specific and development-specific manner, altering GA biosynthesis
      and catabolism gene expression and plant phenotype. PsGA3ox1 transgenic plants
      had longer internodes, tendrils, and fruits, larger stipules, and displayed
      delayed flowering, increased apical meristem life, and altered vascular
      development relative to the null controls. Transgenic PsGA3ox1 overexpression
      lines were then compared with lines where endogenous PsGA3ox1 (LE) was
      introduced, by a series of backcrosses, into the same genetic background (BC
      LEle). Most notably, the BC LEle plants had substantially longer internodes
      containing much greater GA1 levels than the transgenic PsGA3ox1 plants. Induction
      of expression of the GA deactivation gene PsGA2ox1 appears to make an important
      contribution to limiting the increase of internode GA1 to modest levels for the
      transgenic lines. In contrast, PsGA3ox1 (LE) expression driven by its endogenous
      promoter was coordinated within the internode tissue to avoid feed-forward
      regulation of PsGA2ox1, resulting in much greater GA1 accumulation. These studies
      further our fundamental understanding of the regulation of GA biosynthesis and
      catabolism at the tissue and organ level and demonstrate that the
      timing/localization of GA3ox expression within an organ affects both GA
      homeostasis and GA1 levels, and thereby growth. 

PMID- 23979970
TI  - Antiphase light and temperature cycles affect PHYTOCHROME B-controlled ethylene
      sensitivity and biosynthesis, limiting leaf movement and growth of Arabidopsis.
AB  - In the natural environment, days are generally warmer than the night, resulting
      in a positive day/night temperature difference (+DIF). Plants have adapted to
      these conditions, and when exposed to antiphase light and temperature cycles
      (cold photoperiod/warm night [-DIF]), most species exhibit reduced elongation
      growth. To study the physiological mechanism of how light and temperature cycles
      affect plant growth, we used infrared imaging to dissect growth dynamics under
      +DIF and -DIF in the model plant Arabidopsis (Arabidopsis thaliana). We found
      that -DIF altered leaf growth patterns, decreasing the amplitude and delaying the
      phase of leaf movement. Ethylene application restored leaf growth in -DIF
      conditions, and constitutive ethylene signaling mutants maintain robust leaf
      movement amplitudes under -DIF, indicating that ethylene signaling becomes
      limiting under these conditions. In response to -DIF, the phase of ethylene
      emission advanced 2 h, but total ethylene emission was not reduced. However,
      expression analysis on members of the 1-aminocyclopropane-1-carboxylic acid (ACC)
      synthase ethylene biosynthesis gene family showed that ACS2 activity is
      specifically suppressed in the petiole region under -DIF conditions. Indeed,
      petioles of plants under -DIF had reduced ACC content, and application of ACC to
      the petiole restored leaf growth patterns. Moreover, acs2 mutants displayed
      reduced leaf movement under +DIF, similar to wild-type plants under -DIF. In
      addition, we demonstrate that the photoreceptor PHYTOCHROME B restricts ethylene
      biosynthesis and constrains the -DIF-induced phase shift in rhythmic growth. Our
      findings provide a mechanistic insight into how fluctuating temperature cycles
      regulate plant growth. 

PMID- 23979971
TI  - Arabidopsis phospholipase ddelta is involved in basal defense and nonhost
      resistance to powdery mildew fungi.
AB  - Plants have evolved a complex array of defensive responses against pathogenic
      microorganisms. Recognition of microbes initiates signaling cascades that
      activate plant defenses. The membrane lipid phosphatidic acid, produced by
      phospholipase D (PLD), has been shown to take part in both abiotic and biotic
      stress signaling. In this study, the involvement of PLD in the interaction
      between Arabidopsis (Arabidopsis thaliana) and the barley powdery mildew fungus
      Blumeria graminis f. sp. hordei (Bgh) was investigated. This nonadapted pathogen
      is normally resisted by a cell wall-based defense, which stops the fungal hyphae
      from penetrating the epidermal cell wall. Chemical inhibition of phosphatidic
      acid production by PLD increased the penetration rate of Bgh spores on wild-type
      leaves. The analysis of transfer DNA knockout lines for all Arabidopsis PLD genes
      revealed that PLDdelta is involved in penetration resistance against Bgh, and
      chemical inhibition of PLDs in plants mutated in PLDdelta indicated that this
      isoform alone is involved in Bgh resistance. In addition, we confirmed the
      involvement of PLDdelta in penetration resistance against another nonadapted pea
      powdery mildew fungus, Erysiphe pisi. A green fluorescent protein fusion of
      PLDdelta localized to the plasma membrane at the Bgh attack site, where it
      surrounded the cell wall reinforcement. Furthermore, in the plddelta mutant,
      transcriptional up-regulation of early microbe-associated molecular pattern
      response genes was delayed after chitin stimulation. In conclusion, we propose
      that PLD is involved in defense signaling in nonhost resistance against powdery
      mildew fungi and put PLDdelta forward as the main isoform participating in this
      process. 

PMID- 23979973
TI  - Navigating reimbursement for home parenteral nutrition.
AB  - Reimbursement for home parenteral nutrition (HPN) is important for nutrition
      support clinicians to understand. This intent of this review is to provide
      nutrition support clinicians knowledge on navigating through the structured
      requirements of diagnosis driven billing to receive reimbursement for services
      related to HPN, provide information on coding, provide practical tips for
      surviving a Medicare billing audit, and discuss challenges of Medicare guidelines
      seen in clinical practice. 

PMID- 23979972
TI  - The pharmacology of TUG-891, a potent and selective agonist of the free fatty
      acid receptor 4 (FFA4/GPR120), demonstrates both potential opportunity and
      possible challenges to therapeutic agonism.
AB  - TUG-891 [3-(4-((4-fluoro-4'-methyl-[1,1'-biphenyl]-2-yl)methoxy)phenyl)propanoic
      acid] was recently described as a potent and selective agonist for the long chain
      free fatty acid (LCFA) receptor 4 (FFA4; previously G protein-coupled receptor
      120, or GPR120). Herein, we have used TUG-891 to further define the function of
      FFA4 and used this compound in proof of principle studies to indicate the
      therapeutic potential of this receptor. TUG-891 displayed similar signaling
      properties to the LCFA alpha-linolenic acid at human FFA4 across various assay
      end points, including stimulation of Ca2+ mobilization, beta-arrestin-1 and beta
      arrestin-2 recruitment, and extracellular signal-regulated kinase
      phosphorylation. Activation of human FFA4 by TUG-891 also resulted in rapid
      phosphorylation and internalization of the receptor. While these latter events
      were associated with desensitization of the FFA4 signaling response, removal of
      TUG-891 allowed both rapid recycling of FFA4 back to the cell surface and
      resensitization of the FFA4 Ca2+ signaling response. TUG-891 was also a potent
      agonist of mouse FFA4, but it showed only limited selectivity over mouse FFA1,
      complicating its use in vivo in this species. Pharmacologic dissection of
      responses to TUG-891 in model murine cell systems indicated that activation of
      FFA4 was able to mimic many potentially beneficial therapeutic properties
      previously reported for LCFAs, including stimulating glucagon-like peptide-1
      secretion from enteroendocrine cells, enhancing glucose uptake in 3T3-L1
      adipocytes, and inhibiting release of proinflammatory mediators from RAW264.7
      macrophages, which suggests promise for FFA4 as a therapeutic target for type 2
      diabetes and obesity. Together, these results demonstrate both potential but also
      significant challenges that still need to be overcome to therapeutically target
      FFA4.

PMID- 23979974
TI  - Moving fecal microbiota transplantation into the mainstream.
AB  - In recent years, fecal microbiota transplantation (aka fecal transplantation,
      fecal bacteriotherapy, FMT) has become increasing utilized to treat recurrent and
      refractory Clostridium difficile infection (CDI). Almost 600,000 cases of CDI
      occur each year in the United States. Of these, an estimated 15,000 patients have
      a recurrence. The management of recurrent disease has been challenging for
      patients and clinicians. Increasingly, FMT has been recognized as an effective
      option for these patients. This article explores why FMT has reemerged as a
      practical therapeutic modality. In the process, the logistics by which the
      procedure is performed and the factors that may affect quality, safety, and
      patient outcomes will be described. 

PMID- 23979975
TI  - Association between FAS 1377G>A polymorphism and breast cancer susceptibility: a
      meta-analysis.
AB  - Published studies on the association between FAS 1377G>A polymorphism and breast
      cancer susceptibility were inconclusive. To derive a more precise assessment of
      the association, a meta-analysis of published studies was performed. PubMed,
      Embase, and Web of Science were searched for eligible studies on the association
      between FAS 1377G>A polymorphism and breast cancer susceptibility. Five studies
      with a total of 2,905 cases and 3,090 controls were included into the meta
      analysis. Overall, FAS 1377G>A polymorphism was significantly associated with
      increased susceptibility to breast cancer (for AA versus GG: odds ratio (OR) =
      1.39, 95% confidence interval (95% CI) 1.12-1.72, P = 0.003; for AA/GA versus GG:
      OR = 1.18, 95% CI 1.06-1.32, P = 0.004; for AA versus GG/GA: OR = 1.28, 95% CI
      1.05-1.56, P = 0.015). Subgroup analysis by ethnicity found that FAS 1377G>A
      polymorphism was significantly associated with increased susceptibility to breast
      cancer in Asians (for AA versus GG: OR = 1.48, 95% CI 1.16-1.89, P = 0.001; for
      AA/GA versus GG: OR = 1.24, 95% CI 1.06-1.46, P = 0.008; for AA versus GG/GA: OR
      = 1.35, 95% CI 1.08-1.69, P = 0.008), but the association was not found in
      Caucasians. Therefore, the findings of the meta-analysis suggest that FAS 1377G>A
      polymorphism is significantly associated with increased susceptibility to breast
      cancer in Asians.

PMID- 23979976
TI  - Association of the interleukin-4Ralpha rs1801275 and rs1805015 polymorphisms with
      glioma risk.
AB  - Potential single-nucleotide polymorphisms (SNPs) of interleukin-4 receptor alpha
      (IL-4Ralpha) rs1801275 and rs1805015 have been implicated in glioma risk;
      however, the findings of previous published case-control studies are conflicting
      and inconclusive. We performed the updated meta-analysis with the aim to provide
      a more precise estimate for the role of interleukin-4Ralpha SNPs in glioma risk.
      The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to
      evaluate the strength of the gene association. Overall, the pooled analysis
      showed that the IL-4Ralpha rs1801275 polymorphism was associated with a decreased
      risk of glioma in the comparison of G vs. A (OR = 0.87, 95% CI = 0.76-0.99, P OR
      = 0.041). Subgroup analysis by ethnicity revealed that the IL-4Ralpha rs1801275
      variant G and GG + AG exerted a decreased risk effect on the development of
      glioma among Asians, but not Caucasians (G vs. A, OR = 0.81, 95% CI = 0.69-0.95,
      P OR = 0.011; GG + AG vs. AA, OR = 0.80, 95% CI = 0.66-0.96, P OR = 0.018).
      However, the IL-4Ralpha rs1805015 polymorphism did not modify the risk of glioma.
      Sensitivity analysis confirmed the reliability for all of the results. Our meta
      analysis suggests that the polymorphism of IL-4Ralpha rs1801275 but not IL
      4Ralpha rs1805015 plays a protective role in the glioma pathogenesis,
      particularly among Asians.

PMID- 23979977
TI  - NBS1 Glu185Gln polymorphism and cancer risk: update on current evidence.
AB  - A number of studies have investigated the association between NBS1 Glu185Gln
      (rs1805794, E185Q) polymorphism and cancer risk, but the results remained
      controversial. Previous meta-analysis found a borderline significant impact of
      this polymorphism on cancer risk; however, the result might be relatively
      unreliable due to absence of numerous newly published studies. Thus, we conducted
      an updated meta-analysis. A systematic search was performed in PubMed and Embase
      databases until April 9, 2013. The odds ratios were pooled by the fixed
      effects/random-effects model in STATA 12.0 software. As a result, a total of 48
      case-control studies with 17,159 cases and 22,002 controls were included. No
      significant association was detected between the Glu185Gln polymorphism and
      overall cancer risk. As to subgroup analysis by cancer site, the results showed
      that this polymorphism could increase the risk for leukemia and nasopharyngeal
      cancer. Notably, the Glu185Gln polymorphism was found to be related to increased
      risk for urinary system cancer, but decreased risk for digestive system cancer.
      No significant associations were obtained for other subgroup analyses such as
      ethnicity, sample size and smoking status. In conclusion, current evidence did
      not suggest that the NBS1 Glu185Gln polymorphism was associated with overall
      cancer risk, but this polymorphism might contribute to the risk for some specific
      cancer sites due to potential different mechanisms. More well-designed studies
      are imperative to identify the exact function of this polymorphism in
      carcinogenesis. 

PMID- 23979978
TI  - Polymorphisms in the MDM2 gene and risk of malignant bone tumors: a meta
      analysis.
AB  - There are several studies published to assess the associations of murine double
      minute 2 (MDM2) genetic polymorphisms with risk of malignant bone tumors, but
      they reported contradictory results and failed to confirm a strong and consistent
      association. To assess the evidence regarding the associations of MDM2 genetic
      polymorphisms with the risk of malignant bone tumors, we conducted a meta
      analysis of epidemiological studies. The pooled odds ratio (OR) with its 95%
      confidence intervals (95% CI) was used to assess these possible associations.
      Four studies with a total of 3,958 individuals were finally included the meta
      analysis. Meta-analysis of two studies on MDM2 SNP309 polymorphism showed that
      MDM2 SNP309 polymorphism was associated with an increased risk of malignant bone
      tumors (G versus T: OR = 1.72, 95% CI 1.35-2.20, P < 0.001; GG versus TT: OR =
      2.64, 95% CI 1.59-4.39, P < 0.001; GG/GT versus TT: OR = 1.87, 95% CI 1.33-2.62,
      P < 0.001; GG versus TT/GT: OR = 2.20, 95% CI 1.38-3.51, P = 0.001). Meta
      analysis of those two studies on MDM2 rs1690916 polymorphism showed that MDM2
      rs1690916 minor allele A was associated with decreased risk of malignant bone
      tumors (OR = 0.60, 95% CI 0.46-0.77, P < 0.001). Meta-analyses of available data
      show that there are significant associations of MDM2 SNP309 polymorphism and MDM2
      rs1690916 polymorphism with malignant bone tumors.

PMID- 23979979
TI  - Myeloperoxidase G463A polymorphism and risk of lung cancer.
AB  - Myeloperoxidase (MPO) is a phase I enzyme playing a crucial role in metabolically
      activating a wide range of procarcinogens, such as polycyclic aromatic
      hydrocarbons and aromatic amines. The G463A polymorphism in the promoter region
      of the MPO gene has been indicated in lung cancer risk. To investigate the
      precise association of MPO G463A polymorphism with the lung cancer risk, we
      performed this comprehensive meta-analysis with large available data published to
      date. The included 24 individual studies involving a total of 8,313 cases and
      8,728 controls were identified by searching the PubMed, Embase, and Wanfang
      databases. The crude odds ratios (ORs) and the corresponding 95% confidence
      intervals (CIs) were calculated to estimate the association. Stratified analyses
      by ethnicity, source of controls, smoking status, and histological types were
      also conducted. Overall, the MPO G463A polymorphism was negatively related to the
      development of lung cancer in the following genetic models (A vs. G, OR = 0.90,
      95% CI = 0.82-0.99, P OR = 0.029; GA vs. GG, OR = 0.89, 95% CI = 0.80-0.98, P OR
      = 0.022; AA + GA vs. GG, OR = 0.89, 95% CI = 0.81-0.98, P OR = 0.023). Stratified
      analyses by ethnicity indicated that the variant genotype of MPO G463A was
      associated with a decreased risk of lung cancer in Asians and Caucasians. Similar
      findings were observed among the smokers and population-based case-control
      studies. The MPO G463A polymorphism seemed to exert no effect on lung
      adenocarcinoma and squamous cell carcinoma. The comprehensive meta-analysis shows
      that the polymorphism of MPO G463A is a protective factor for lung cancer,
      particularly among the populations of Asians, Caucasians, and smokers.

PMID- 23979980
TI  - Quantitative assessment of the influence of glutathione S-transferase T1 null
      variant on gastric cancer risk.
AB  - Glutathione S-transferase T1 (GSTT1) catalyzes reactions between glutathione and
      lipophilic compounds with electrophilic centers, leading to neutralization of
      toxic compounds, xenobiotics, and products of oxidative stress. In the past
      decade, a number of case-control studies have been carried out to investigate the
      relationship between the GSTT1 null polymorphism and gastric cancer (GC), but the
      results have been inconclusive. To investigate this inconsistency, we performed a
      meta-analysis of 46 studies involving a total of 9012 GC cases and 14,215
      controls for null variant of the GSTT1 gene to evaluate the effect of GSTT1 on
      genetic susceptibility for GC. Potential sources of heterogeneity including
      ethnicity, source of control, and sample size were also assessed. Overall,
      significantly increased GC risk was associated with GSTT1 null polymorphism with
      OR of 1.20 (95% CI, 1.10-1.32; P < 0.05). In the subgroup analysis by ethnicity,
      significantly increased risks were found in East Asians and Indians, while no
      significant associations were found among Caucasian, and Middle Eastern and
      African populations. By pooling data from 19 studies that considered combinations
      of GSTT1 and GSTM1 genotypes, a statistically significant increased risk for GC
      (OR = 2.04, 95% CI, 1.49-2.64; P < 0.05) was detected for individuals with dual
      deletion in both genes compared with positive genotypes. In addition, we found
      that cigarette smoking and alcohol drinking may modified the association of GSTT1
      null genotypes with the risk of GC. In conclusion, this meta-analysis suggests
      that GSTT1 null polymorphism is associated with elevated GC risk, but these
      associations vary in different ethnic populations.

PMID- 23979981
TI  - Ubiquitin-specific protease 22: a novel molecular biomarker in cervical cancer
      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 cervical
      cancer. To our knowledge, this is the first study that determines the
      relationship between USP22 expression and clinicopathological significance in
      cervical cancer. The immunohistochemistry results showed that USP22 protein was
      overexpressed in cervical cancer samples compared with normal cervical tissues (P
      < 0.001). Moreover, clinicopathological analysis showed that USP22 expression was
      highly related to International Federation of Gynecology and Obstetrics stage,
      Ki67, lymph node metastasis, and histology grade. The results of Kaplan-Meier
      analysis indicated that patients with high USP22 expression had significantly
      shorter overall survival (OS) and disease-free survival (DFS) than patients with
      low expression of USP22 (P < 0.001). Multivariate Cox regression analysis
      revealed that USP22 expression status was an independent prognostic marker for
      both OS and DFS of patients with cervical cancer. It is suggested that USP22
      overexpression may be associated with poor prognosis in cervical cancer. It may
      represent a novel prognostic biomarker or a target for improving the treatment
      efficiency of patients with cervical cancer.

PMID- 23979982
TI  - The effect of brominated furanones on the formation of Staphylococcus aureus
      biofilm on PVC.
AB  - To study the influence of brominated furanones on the formation of Staphylococcus
      aureus (SA) biofilm on PVC thus providing new avenues of research on the surface
      modification of materials and clinical treatment of biomaterial-centered
      infection. Three brominated furanones (furanone-1, furanone-2, and furanone-3)
      were coated on the surface of PVC material. Both the modified PVC materials and
      SA were co-cultivated together. To assess the thickness of bacterial biofilm and
      bacterium colony unit area on PVC materials, confocal laser scanning microscopy
      and scanning electron microscopy (SEM) were used to observe the surface structure
      of SA biofilm formation. All treatments were compared with the control group
      which was not coated with furanones. PVC materials coated with furanone-1 had an
      increase in bacterial biofilm as well as SA colony area when compared with
      control. However, there was no significant difference between treating with
      furanone-1 and furanone-3 (P > 0.05). The impact of different brominated
      furanones on SA biofilm formation on the surface of PVC materials is different,
      furanone-1 can promote the SA biofilm formation on the surface of PVC material.

PMID- 23979983
TI  - "One-off" complete radiofrequency ablation of hepatocellular carcinoma adjacent
      to the gallbladder by a novel laparoscopic technique without gallbladder
      isolation.
AB  - The main objective of this study is to assess the feasibility and safety of
      treating hepatocellular carcinoma (HCC) proximal to the gallbladder using
      laparoscopic radiofrequency ablation (RFA). Surgical ablation of tumor located
      adjacent to the gallbladder may damage the gallbladder wall, even with a
      laparoscope and this ablation method is not precise and incomplete and is
      frequently combined with alcohol injections with need for further RFA treatment.
      Four patients were included in this study, with typical HCC where the tumor was
      present on the left, right, or bed side surrounding the gallbladder. The
      gallbladder was not separated or removed during larascopic inspection. In the RFA
      treatment procedure, the tumor lesion was pre-heated for 10 min, and heating was
      continued for 20 min. The integrity of the gallbladder wall was properly
      maintained. A follow-up to check for possible local recurrence was carried out 1
      year after the RFA. The goal of "one-off" tumor complete RFA is to achieve
      thorough ablation of the tumor in a single treatment and limiting the possibility
      of recurrence within 6 months. Seven days after RFA, liver functions of all the
      patients returned to near-preoperative levels. The patients experienced slight
      pain in the upper right abdomen, which disappeared in 2-3 days. Results of B
      ultrasound on days 3-5 showed thickening of the periphery of the ablation area,
      without significant effusion. Enhanced CT on day 3 showed that RFA low-density
      area completely covered the lesions. No significant abnormality was observed in
      the gallbladder and its vicinity. One month after the surgery, B ultrasound and
      CT examination revealed no significant abnormalities. All patients had an intact
      gallbladder, and no extrahepatic or intrahepatic bile duct dilatation occurred.
      There was no evidence of damage to the bile duct or the vessels. Follow-up for 18
      32 months found that all patients were in good condition. "One-off" complete RFA
      can be safely implemented to ablate HCC close to the gallbladder with the
      assistance of a laparoscope while maintaining integrity and continuity of the
      gallbladder, and without the need for secondary treatments.

PMID- 23979984
TI  - Complete radiofrequency ablation of hepatolithiasis-associated cholangiocarcinoma
      and successful management of post-ablation bronchobiliary fistula.
AB  - This report documented the use of radiofrequency ablation (RFA) in the treatment
      of hepatolithiasis-associated cholangiocarcinoma and cyanoacrylate glue in the
      management of post-ablation bronchobiliary fistula. A 47-year-old Chinese woman
      with 20 years history of extrahepatic and intrahepatic cholangiolithiasis and
      multiple hepatic segmentectomy, developed hepatolithiasis-associated
      cholangiocarcinoma. The tumor was successfully treated with RFA but patient
      developed bronchobiliary fistula. Cyanoacrylate glue was used for occluding the
      bronchobiliary fistula. CT scan at 3 months showed complete restoration of
      physiological separation between the biliary and bronchial system. Repeat CT scan
      showed complete tumor ablation with no signs of tumor recurrence 10 months after
      RFA. In conclusion, RFA may be a safe and effective treatment option for patients
      with hepatolithiasis-associated cholangiocarcinoma who are poor candidates for
      surgical resection. Protection of the integrity of the bile duct and diaphragm
      during RFA can minimize postoperative complications. In case of development of
      post-ablation bronchobiliary fistula, cyanoacrylate glue can be used to occlude
      the fistula, before surgical resection is considered.

PMID- 23979985
TI  - WT1 mutation in pediatric patients with acute myeloid leukemia: a report from the
      Japanese Childhood AML Cooperative Study Group.
AB  - Mutations in Wilms tumor 1 (WT1) have been reported in 10-22 % of patients with
      cytogenetically normal acute myeloid leukemia (CN-AML), but the prognostic
      implications of these abnormalities have not been clarified in either adults or
      children. One hundred and fifty-seven pediatric AML patients were analyzed for
      WT1 mutations around hotspots at exons 7 and 9; however, amplification of the WT1
      gene by the reverse transcriptase-polymerase chain reaction was not completed in
      four cases (2.5 %). Of the 153 evaluable patients, 10 patients (6.5 %) had a
      mutation in WT1. The incidence of WT1 mutations was significantly higher in CN
      AML than in others (15.2 vs. 4.5 %, respectively, P = 0.03). Of the 10 WT1
      mutated cases, eight (80 %) had mutations in other genes, including FLT3-ITD in
      two cases, FLT3-D835 mutation in two, KIT mutation in three, MLL-PTD in three,
      NRAS mutation in one, and KRAS mutation in two (in some cases, more than one
      additional gene was mutated). The incidences of KIT and FLT3-D835 mutations were
      significantly higher in patients with than in those without WT1 mutation. No
      significant differences were observed in the 3-year overall survival and disease
      free survival; however, the presence of WT1 mutation was related to a poor
      prognosis in patients with CN-AML, excluding those with FLT3-ITD and those
      younger than 3 years.

PMID- 23979986
TI  - First serial in vivo results of mechanical circulatory support in children with a
      new diagonal pump.
AB  - OBJECTIVES: Mechanical circulatory support (MCS) is a rescue therapy for infants
      and children suffering from severe cardiorespiratory failure with specific system
      related complications like bleeding, thromboembolism and device failure. Novel
      circuit components for temporary MCS with improved haemodynamic properties may
      improve patients' outcome and reduce system-related morbidities. The Deltastream
      DP3 (Medos Medizintechnik AG, Stolberg, Germany) is a newly designed rotational
      pump with a diagonally streamed impeller that can be used in children of all ages
      (priming volume 16 ml, flow 0-8 l/min). The aim of this study was to analyse the
      feasibility and safety of the DP3 pump system in children. METHODS: We
      retrospectively investigated a consecutive series of 16 children [median age 0.9
      months (0.1-55 months), median weight 3.2 kg (2.5-14 kg)]. The DP3 circuit was
      used 22 times in these children for different indications: (I) extracorporeal
      life support (ECLS) in post-cardiotomy heart failure (n = 11), (II) ECLS in
      cardiopulmonary resuscitation (CPR) (n = 7) and (III) extracorporeal membrane
      oxygenation (ECMO) in acute respiratory distress syndrome (ARDS) (n = 4).
      RESULTS: Median duration of MCS was 4 days (0-18 days), 12 patients (75%) were
      weaned successfully from MCS, 4 of these children (25%) died after weaning, with
      a median survival time of 15 days (6-28 days). Overall survival rate was 50% and
      all 8 survivors were discharged home without neurological injury. There was no
      case of severe bleeding, thromboembolic complications or device failure. Mean
      lactate dehydrogenase (LDH) before MCS was 700 (+/-384) U/l, and increased to a
      maximum of 2279 (+/-2635) U/l during MCS (P = 0.04). Baseline D-dimer values were
      3.4 (+/-3.0) mg/l and rose significantly to 19.5 (+/-11.5) mg/l during MCS (P <
      0.001). The mean of the highest plasma-free haemoglobin during MCS was 21.0 (+/
      42.9) mg/dl. The increase in plasma-free haemoglobin correlated moderately with
      the duration of MCS (Pearson's r: 0.78). CONCLUSION: The use of the Deltastream
      DP3 seems to be safe and effective for MCS in children and may show a low degree
      of haemolysis. We observed no system-related complications and an overall good
      outcome in this demanding patient cohort.

PMID- 23979987
TI  - Significance of the serum carcinoembryonic antigen level during the follow-up of
      patients with completely resected non-small-cell lung cancer.
AB  - OBJECTIVES: The purpose of this study was to elucidate the detectability of
      recurrence and the prognostic significance of the serum carcinoembryonic antigen
      (CEA) levels in patients with completely resected non-small-cell lung cancer
      (NSCLC). METHODS: Five hundred and eighteen NSCLC patients who underwent complete
      resection at Aichi Cancer Center between April 2001 and March 2006 were enrolled
      in this study. The patient characteristics were as follows: the median age was 63
      years; 331 tumours were classified as pathological stage I, 88 tumours were
      pathological stage II and 99 tumours were pathological stage III; 140 tumours
      were adenocarcinomas with epidermal growth factor receptor (EGFR) mutations, 268
      tumours were adenocarcinomas with EGFR wild-type mutations and 110 tumours were
      other NSCLCs. The patients were divided into three groups: those with a normal
      CEA level before and 1-3 months after surgery (N group, n = 380), those with an
      elevated CEA level before surgery and a normal CEA level 1-3 months after surgery
      (HN group, n = 105) and those with an elevated CEA level 1-3 months after surgery
      regardless of the preoperative CEA level (H group, n = 33). The correlations
      between the changes in the serum CEA levels and the clinical outcomes were
      analysed. RESULTS: Recurrence developed in 122 patients (32%) in the N group, 49
      patients (47%) in the HN group and 19 patients (58%) in the H group (P = 0.001).
      The sensitivity and specificity of an elevated serum CEA level during the follow
      up period for detecting recurrence were 30 and 98% in the N group and 82 and 73%
      in the HN group, respectively. Twenty-seven asymptomatic recurrent tumours
      combined with an elevated serum CEA level were detected in the HN group. In the
      multivariate Cox regression analysis, the serum CEA level 1-3 months after
      surgery had prognostic value for overall survival. CONCLUSIONS: In completely
      resected NSCLC patients, measuring the serum CEA level during the follow-up
      period is useful in patients in whom an elevated level normalizes after surgery,
      and the serum CEA level 1-3 months after surgery is considered to have prognostic
      significance regarding survival.

PMID- 23979988
TI  - Long-term outcomes and comparison after conventional coronary artery bypass
      grafting for left main disease between patients classified as percutaneous
      coronary intervention recommendation classes II and III.
AB  - OBJECTIVES: We retrospectively analysed long-term outcomes after conventional
      coronary artery bypass grafting (CABG) between patients having left main (LM)
      disease who should have been assigned class II and those assigned class III
      recommendation for percutaneous coronary intervention (PCI) according to the 2010
      European Society of Cardiology and the European Association for Cardio-Thoracic
      Surgery guidelines. METHODS: From January 2000 to December 2009, conventional
      CABG was routinely employed in 180 consecutive patients with previously untreated
      and stable LM lesion. A comparison between two groups (CABG for PCI class II and
      CABG for PCI class III) was performed, looking at the primary endpoint of major
      adverse cardiac and cerebrovascular events (MACCE), including all-cause death,
      stroke [cerebral vascular accident (CVA)], myocardial infarction (MI) and repeat
      revascularization. We also analysed the effects of variables on MACCE at 8 years
      after the operation. RESULTS: The overall 8-year MACCE rates were significantly
      lower in the CABG for PCI class II group than in the CABG for PCI class III group
      (9.7% class II vs 31.1% class III; P = 0.0005). This was largely because of an
      increased rate of repeat revascularization (1.2% class II vs 13.8% class III; P =
      0.0029). The cumulative rate of the combined outcomes of all death/CVA/MI was
      significantly lower in the CABG for PCI class II group (8.5% class II vs 19.2%
      class III; P = 0.048); there was no observed difference between the groups for
      all-cause death, CVA and MI. The SYNTAX score was demonstrated to be the only
      significant predictor of combined outcomes (Death/CVA/MI) at 8 years [odds ratio
      (OR) 1.05, P = 0.023], repeat revascularization at 8 years (OR 1.11, P = 0.0013)
      and MACCE at 8 years (OR 1.07, P < 0.0001). CONCLUSIONS: In our routine strategy
      of conventional CABG for LM disease, patients believed to be PCI candidates for
      LM disease have significantly better long-term outcomes as characterized by
      combined outcomes (Death/CVA/MI), repeat revascularization and MACCE. These
      results provide a suitable benchmark against which long-term outcomes of PCI for
      LM disease can be compared. The SYNTAX score, which was introduced to determine
      treatment for complex coronary disease, is indicative of long-term outcomes after
      CABG for LM disease.

PMID- 23979989
TI  - Three-dimensional computed tomography reveals anatomical variant of meandering
      pulmonary vein.

PMID- 23979990
TI  - Beyond the "general public": implications of audience characteristics for
      promoting species conservation in the Western Ghats hotspot, India.
AB  - Understanding how different audience groups perceive wildlife is crucial for the
      promotion of biodiversity conservation, especially given the key role of flagship
      species in conservation campaigns. Although the heterogeneity in preferences
      reinforces the need for campaigns tailored to specific target audiences, many
      conservation education and awareness campaigns still claim to target the "general
      public". Audiences can be segmented according to social, economic, and cultural
      criteria across which species perceptions are known to vary. Different studies
      have investigated the preferences of different groups towards certain wildlife
      species, but these are largely confined to a single conservation stakeholder
      group, such as tourists, local communities, or potential donors in western
      countries. In this study, we seek to determine from a multi-stakeholder
      perspective, audience characteristics that influence perceptions towards wildlife
      at Valparai, a fragmented plateau in the Western Ghats region of the Western
      Ghats-Sri Lanka Hotspot. We found that stakeholder group membership was the most
      important characteristic followed by gender. While some characteristics had a
      wide-scale effect others were restricted to a few species. Our results emphasize
      the need to design conservation campaigns with specific audiences in mind,
      instead of the very often referred to "general public". 

PMID- 23979991
TI  - HspA1A facilitates DNA repair in human bronchial epithelial cells exposed to
      Benzo[a]pyrene and interacts with casein kinase 2.
AB  - Benzo[a]pyrene (BaP) is a ubiquitously distributed environmental pollutant that
      induces deoxyribonucleic acid (DNA) damage. The inducible heat shock protein
      (HspA1A) can function as a molecular chaperone; however, its role in DNA repair
      remains largely unknown. In the present study, human bronchial epithelial cells
      (16HBE) stably transfected with plasmids carrying HspA1A gene or shRNAs against
      HspA1A were treated with BaP. DNA damage levels of the cells were evaluated by
      comet assay. Results suggest that HspA1A could protect cells against DNA damage
      and facilitate the decrease of DNA damage levels during the first 2 h of DNA
      repair. DNA repair capacity (DRC) of Benzo(a)pyrene diol epoxide (BPDE)-DNA
      adducts was evaluated by host cell reactivation assay in the stable 16HBE cells
      transfected with luciferase reporter vector PCMVluc pretreated with BPDE.
      Compared with control cells, cells overexpressing HspA1A showed higher DRC (p <
      0.01 at 10 MUM BPDE and p < 0.05 at 20 MUM BPDE, respectively), while knockdown
      of HspA1A inhibited DNA repair (p < 0.05 at 10 MUM BPDE). Moreover, casein kinase
      2 (CK2) was shown to interact with HspA1A by mass spectrometry and co
      immunoprecipitation assays. The two proteins were co-localized in the cell
      nucleus and perinuclear region during DNA repair, and were identified by confocal
      laser scanning microscope. In addition, cells overexpressing HspA1A showed an
      increased CK2 activity after BaP treatment compared with control cells (p <
      0.01). Our results suggest that HspA1A facilitates DNA repair after BaP
      treatment. HspA1A also interacts with CK2 and enhances the kinase activities of
      CK2 during DNA repair. 

PMID- 23979992
TI  - Proteomics strategies to identify SUMO targets and acceptor sites: a survey of
      RNA-binding proteins SUMOylation.
AB  - SUMOylation is a protein posttranslational modification that participates in the
      regulation of numerous biological processes within the cells. Small ubiquitin
      like modifier (SUMO) proteins are members of the ubiquitin-like protein family
      and, similarly to ubiquitin, are covalently linked to a lysine residue on a
      target protein via a multi-enzymatic cascade. To assess the specific mechanism
      triggered by SUMOylation, the identification of SUMO protein substrates and of
      the precise acceptor site to which SUMO is bound is of critical relevance.
      Despite hundreds of mammalian proteins have been described as targets of
      SUMOylation, the identification of the precise acceptor sites still represents an
      important analytical challenge because of the relatively low stoichiometry in
      vivo and the highly dynamic nature of this modification. Moreover, mass
      spectrometry-based identification of SUMOylated sites is hampered by the large
      peptide remnant of SUMO proteins that are left on the modified lysine residue
      upon tryptic digestion. The present review provides a survey of the strategies
      that have been exploited in order to enrich, purify and identify SUMOylation
      substrates and acceptor sites in human cells on a large-scale format. The success
      of the presented strategies helped to unravel the numerous activities of this
      modification, as it was shown by the exemplary case of the RNA-binding protein
      family, whose SUMOylation is here reviewed. 

PMID- 23979995
TI  - Interventions for erythropoietin-resistant anaemia in dialysis patients.
AB  - BACKGROUND: People living with end-stage kidney disease (ESKD) often develop
      anaemia. Erythropoiesis-simulating agents (ESAs) are often given to people living
      with ESKD to maintain haemoglobin at a level to minimise need for transfusion.
      However, about 5% to 10% of patients with ESKD exhibit resistance to ESAs, and
      observational studies have shown that patients requiring high doses of ESA are at
      increased risk of mortality. OBJECTIVES: This review aimed to study the effects
      of interventions for the treatment of ESA-resistant anaemia in people with ESKD.
      SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE and EMBASE for randomised controlled trials (RCT) that
      involved participants with ESKD on dialysis or who were pre-dialysis patients
      with chronic kidney disease (stage 5). Date of last search: April 2013. SELECTION
      CRITERIA: ESA resistance was defined as failure to achieve or maintain
      haemoglobin/haematocrit levels within the desired target range despite
      appropriate ESA doses (erythropoietin >= 450 U/kg/wk intravenously or >= 300
      U/kg/wk subcutaneously; darbepoetin >= 1.5 ug/kg/wk) in people who were not
      nutritionally deficient, or who had haematological or bleeding disorders.
      Extended inclusion criteria for ESA hyporesponsive state were: erythropoietin
      dose >= 300 U/kg/wk and >= 150 U/kg/wk for intravenous administration; or >= 200
      U/kg/wk and >= 100 U/kg/wk for subcutaneous administration; or darbepoetin dose
      >= 1.0 ug/kg/wk). DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed study quality and extracted data. Statistical analyses were performed
      using a random effects model and results expressed as risk ratio (RR) or mean
      difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: Titles and
      abstracts of 521 records were screened, of which we reviewed 99 from the full
      text. Only two studies matched our inclusion criteria. One study compared
      intravenous vitamin C versus no study medication for six months in 42 ESKD
      patients on haemodialysis who required intravenous erythropoietin (dose >= 450
      U/kg/wk). The other included study compared high-flux dialyser versus low-flux
      dialyser for six months in 48 haemodialysis patients who required subcutaneous
      erythropoietin (dose >= 200 U/kg/wk). Because interventions differed, data could
      not be combined for quantitative meta-analysis. AUTHORS' CONCLUSIONS: There was
      inadequate evidence identified to inform recommendation of any intervention to
      ameliorate ESA hyporesponsiveness. Adequately powered RCTs are required to
      establish the safety and efficacy of interventions to improve responsiveness to
      ESA therapy.

PMID- 23979993
TI  - SUMO and Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by
      progressive cognitive decline and is the most common cause of dementia in the
      elderly. Histopathologically, AD features insoluble aggregates of two proteins in
      the brain, amyloid-beta (Abeta) and the microtubule-associated protein tau, both
      of which have been linked to the small ubiquitin-like modifier (SUMO). A large
      body of research has elucidated many of the molecular and cellular pathways that
      underlie AD, including those involving the abnormal Abeta and tau aggregates.
      However, a full understanding of the etiology and pathogenesis of the disease has
      remained elusive. Consequently, there are currently no effective therapeutic
      options that can modify the disease progression and slow or stop the decline of
      cognitive functioning. As part of the effort to address this lacking, there needs
      a better understanding of the signaling pathways that become impaired under AD
      pathology, including the regulatory mechanisms that normally control those
      networks. One such mechanism involves SUMOylation, which is a post-translational
      modification (PTM) that is involved in regulating many aspects of cell biology
      and has also been found to have several critical neuron-specific roles. Early
      studies have indicated that the SUMO system is likely altered with AD-type
      pathology, which may impact Abeta levels and tau aggregation. Although still a
      relatively unexplored topic, SUMOylation will likely emerge as a significant
      factor in AD pathogenesis in ways which may be somewhat analogous to other
      regulatory PTMs such as phosphorylation. Thus, in addition to the upstream
      effects on tau and Abeta processing, there may also be downstream effects
      mediated by Abeta aggregates or other AD-related factors on SUMO-regulated
      signaling pathways. Multiple proteins that have functions relevant to AD
      pathology have been identified as SUMO substrates, including those involved in
      synaptic physiology, mitochondrial dynamics, and inflammatory signaling. Ongoing
      studies will determine how these SUMO-regulated functions in neurons and glial
      cells may be impacted by Abeta and AD pathology. Here, we present a review of the
      current literature on the involvement of SUMO in AD, as well as an overview of
      the SUMOylated proteins and pathways that are potentially dysregulated with AD
      pathogenesis. 

PMID- 23979996
TI  - High-throughput fluorescence-based screen to identify factors involved in nuclear
      receptor recruitment to response elements.
AB  - The glucocorticoid receptor is an inducible transcription factor which plays
      important roles in many -physiological processes. Upon activation, GR interacts
      with regulatory elements and modulates the expression of genes. Although GR is
      widely expressed in multiple tissues, its binding sites within chromatin and the
      genes it regulates are tissue specific. Many accessory proteins and cofactors are
      thought to play a role in dictating GR's function; however, mechanisms involved
      in targeting GR to specific sites in the genome are not well understood. Here we
      describe a high-throughput fluorescence-based method to identify factors involved
      in GR loading at response elements. This screen utilizes a genetically engineered
      cell line that contains 200 repeats of a glucocorticoid response promoter and
      expresses GFP-tagged GR. Upon treatment with corticosteroids, GFP-GR forms a
      steady-state distribution at the promoter array, and its concentration at this
      focal point can be quantitatively determined. This system provides a novel
      approach to identify activities important for GR loading at its response element
      using siRNA libraries to target factors that enhance or inhibit receptor
      localization. 

PMID- 23979997
TI  - Live-cell imaging combined with immunofluorescence, RNA, or DNA FISH to study the
      nuclear dynamics and expression of the X-inactivation center.
AB  - Differentiation of embryonic stem cells is accompanied by changes of gene
      expression and chromatin and chromosome dynamics. One of the most impressive
      examples for these changes is inactivation of one of the two X chromosomes
      occurring upon differentiation of mouse female embryonic stem cells. With a few
      exceptions, these events have been mainly studied in fixed cells. In order to
      better understand the dynamics, kinetics, and order of events during
      differentiation, one needs to employ live-cell imaging techniques. Here, we
      describe a combination of live-cell imaging with techniques that can be used in
      fixed cells (e.g., RNA FISH) to correlate locus dynamics or subnuclear
      localization with, e.g., gene expression. To study locus dynamics in female ES
      cells, we generated cell lines containing TetO arrays in the X-inactivation
      center, the locus on the X chromosome regulating X-inactivation, which can be
      visualized upon expression of TetR fused to fluorescent proteins. We will use
      this system to elaborate on how to generate ES cell lines for live-cell imaging
      of locus dynamics, how to culture ES cells prior to live-cell imaging, and to
      describe typical live-cell imaging conditions for ES cells using different
      microscopes. Furthermore, we will explain how RNA, DNA FISH, or
      immunofluorescence can be applied following live-cell imaging to correlate gene
      expression with locus dynamics. 

PMID- 23979998
TI  - Single-molecule resolution fluorescent in situ hybridization (smFISH) in the
      yeast S. cerevisiae.
AB  - Regulating gene expression is a major task for all cellular systems. RNA
      production and degradation plays a critical role in this process and accurately
      measuring cellular mRNA levels is essential to understanding gene expression
      regulation. Classical biochemical assays that study gene expression rely on
      extracting RNAs from large populations of cells, taking them out of their native
      context and thereby losing spatial information as well as cell-to-cell
      variability. In this chapter, we describe a fluorescent in situ hybridization
      (FISH) technique that circumvents this problem by detecting single RNAs in single
      cells. The technique employs multiple single-stranded short DNA probes
      fluorescently labeled with organic dyes that hybridize to target RNAs in fixed
      cells, allowing quantification and localization of RNAs at the single-cell level
      and at single-molecule resolution. The protocol described here has been optimized
      for the yeast S. cerevisiae. 

PMID- 23979999
TI  - Measuring transcription dynamics in living cells using fluctuation analysis.
AB  - Single-cell studies of gene regulation suggest that transcription dynamics play a
      fundamental role in determining expression heterogeneity within a population. In
      addition, the three-dimensional organization of the nucleus seems to both reflect
      and influence expression patterns in the cell. Therefore, to gain a holistic
      understanding of transcriptional regulation, it is necessary to develop methods
      for studying transcription of single genes in living cells with high spatial and
      temporal resolution. In this chapter, we describe a recently developed approach
      for visualizing and quantifying pre-mRNA synthesis at a single active gene in the
      nucleus. The approach is based on the high-affinity interaction between MS2/PP7
      bacteriophage coat proteins and RNA hairpins which are transcribed by the gene of
      interest. The MS2/PP7 coat protein is fused to a fluorescent protein and binds
      the nascent mRNA, allowing for detection of single transcription events in the
      fluorescence microscope. By time-lapse fluorescence imaging and quantitative
      image analysis, one can generate a time trace of fluorescence intensity at the
      site of transcription. By temporal autocorrelation analysis, one can determine
      enzymatic activities of RNAP such as initiation rate and elongation rate. In this
      protocol, we summarize the experimental concept, design, and execution for real
      time observation of transcription in living cells.

PMID- 23980000
TI  - Tracking nuclear poly(A) RNA movement within and among speckle nuclear bodies and
      the surrounding nucleoplasm.
AB  - The movement of polyadenylated RNA transcripts (poly(A) RNA) through speckles in
      the nucleus can be detected and studied using fluorescence correlation microscopy
      (FCM) and photoactivation RNA tracking techniques. Speckles, sometimes called
      interchromatin granule clusters, are nuclear bodies that contain pre-mRNA
      splicing factors and poly(A) RNA. In the methods described here, speckles are
      marked in live cells using monomeric red fluorescent protein fused to SC35, a
      splicing protein that is a common speckle component. Endogenous poly(A) RNAs are
      tagged by in vivo hybridization with fluorescein-labeled oligo(dT) and FCM is
      performed at the marked speckles and in the nucleoplasm to measure the mobility
      of the tagged poly(A) RNA. The majority of the nuclear poly(A) RNA population
      diffuses rapidly throughout the nucleoplasm, and thus this method allows one to
      ask whether poly(A) RNA that is located in speckles at a given time is undergoing
      a dynamic transit or is, in contrast, a more immobile, perhaps structural,
      component. To visualize the movement of poly(A) RNA away from speckles, poly(A)
      RNA is tagged with caged-fluorescein-labeled oligo(dT) and speckle-associated
      poly(A) RNAs are specifically photoactivated using a laser beam directed through
      a pinhole in a rapid digital imaging microscopy system. The spatial distribution
      of the now-fluorescent RNA as it moves from the speckle photoactivation site is
      then recorded over time. Temperature and/or ATP levels can also be varied to test
      whether movement or localization of the poly(A) RNA is dependent on metabolic
      energy. 

PMID- 23979994
TI  - SUMO and Parkinson's disease.
AB  - Parkinson's disease (PD) is one of the most common degenerative disorders of the
      central nervous system that produces motor and non-motor symptoms. The majority
      of cases are idiopathic and characterized by the presence of Lewy bodies
      containing fibrillar alpha-synuclein. Small ubiquitin-related modifier (SUMO)
      immunoreactivity was observed among others in cases with PD. Key disease
      associated proteins are SUMO-modified, linking this posttranslational
      modification to neurodegeneration. SUMOylation and SUMO-mediated mechanisms have
      been intensively studied in recent years, revealing nuclear and extranuclear
      functions for SUMO in a variety of cellular processes, including the regulation
      of transcriptional activity, modulation of signal transduction pathways, and
      response to cellular stress. This points to a role for SUMO more than just an
      antagonist to ubiquitin and proteasomal degradation. The identification of risk
      and age-at-onset gene loci was a breakthrough in PD and promoted the
      understanding of molecular mechanisms in the pathology. PD has been increasingly
      linked with mitochondrial dysfunction and impaired mitochondrial quality control.
      Interestingly, SUMO is involved in many of these processes and up-regulated in
      response to cellular stress, further emphasizing the importance of SUMOylation in
      physiology and disease. 

PMID- 23980001
TI  - Nuclear trafficking and export of single, native mRNPs in Chironomus tentans
      salivary gland cells.
AB  - Real-time observation of single molecules or biological nanoparticles with high
      spatial resolution in living cells provides detailed insights into the dynamics
      of cellular processes. The salivary gland cells of Chironomus tentans are a well
      established model system to study the processing of RNA and the formation and
      fate of messenger ribonucleoprotein particles (mRNPs). For a long time,
      challenging imaging conditions limited the access to this system for in vivo
      fluorescence microscopy. Recent technical and methodical advantages now allow
      observing even single molecules in these cells. We describe here the experimental
      approach and the optical techniques required to analyze intranuclear trafficking
      and export of single native mRNPs across the nuclear envelope. 

PMID- 23980002
TI  - Single mRNP tracking in living mammalian cells.
AB  - The translocation of single mRNPs (mRNA-protein complexes) from the nucleus to
      the cytoplasm through the nuclear pore complex (NPC) is an important basic
      cellular process. Originally, in order to visualize this process, single mRNP
      export was examined using electron microscopy (EM) in fixed Chironomus tentans
      specimens. These studies described the nucleocytoplasmic translocation of huge
      mRNPs (~30 kb) transcribed from the Balbiani-ring genes. However, knowledge of
      the in vivo mRNP kinetics in cell compartments remained poor up until recently.
      The current use of unique fluorescent protein tags, which are able to bind to
      mRNA transcripts, has allowed the detection and measurements of single mRNP
      kinetics in living cells. This has demonstrated that mRNP movement is affected by
      the size of the transcript and the splicing process. It was found that mRNP rates
      of translocation are slower in the nucleus compared to the cytoplasm and that the
      cell nucleus contains interchromatin tracks in which mRNPs diffuse. In order to
      track single mRNP movement in living cells, it is important to be able to
      identify single mRNP molecules transcribed from a certain gene, at the single
      cell level. Single-molecule analysis of gene expression requires advanced imaging
      systems and analytical software in order to detect and follow the movement of
      single mRNPs. In this chapter we describe the methods required for the detection
      and tracking of single mRNP movement in living mammalian cells. 

PMID- 23980003
TI  - Imaging nascent RNA dynamics in Dictyostelium.
AB  - Dictyostelium cells have great utility for live imaging of single gene
      transcriptional dynamics. The cells allow efficient molecular genetics, for
      targeting of RNA reporters and fluorescent proteins to individual, defined loci.
      Dictyostelium cells share many signalling, chromatin and nuclear characteristics
      of larger eukaryotes, yet the cells have a relatively simple scattered
      differentiation programme, allowing imaging of transcriptional events in the
      context of stochastic developmental choices. This review will detail the methods
      and considerations for imaging nascent RNA dynamics at single genes in living
      Dictyostelium cells.

PMID- 23980004
TI  - Monitoring dynamic binding of chromatin proteins in vivo by single-molecule
      tracking.
AB  - Single-molecule fluorescence microscopy has been used for decades to quantify
      macromolecular dynamics occurring in specimens that are in direct contact with a
      coverslip. This has permitted in vitro analysis of single-molecule motion in
      various biochemically reconstituted systems as well as in vivo studies of single
      molecule motion on cell membranes. More recently, thanks to improvements in
      fluorescent tags and microscopes, it has been possible to follow individual
      molecules inside thicker specimens such as the nucleus of living cells. This has
      enabled a detailed description of the live-cell binding of nuclear proteins to
      DNA. In this protocol we describe a method to quantify intranuclear binding using
      single-molecule tracking (SMT). 

PMID- 23980005
TI  - Single-particle tracking for studying the dynamic properties of genomic regions
      in live cells.
AB  - The appropriate functioning of living cells depends on a variety of dynamic
      processes that necessitate delicate motion, transportation, association, and
      disassociation in time and space. Different dynamic patterns such as directed
      motion, normal diffusion, and restricted diffusion take part at different length
      scales, and their identification serves as a tool for exploring biochemical
      processes. Here we describe single-particle tracking which is a powerful method
      that allows the characterization of dynamic processes on the single-molecule or
      single-particle level with nanometer spatial and sub-second temporal precision.
      In particular, we describe the cell preparation procedures, microscopy imaging,
      and image analysis processes for following telomere dynamics in living mammalian
      cells. 

PMID- 23980006
TI  - Microscopic analysis of chromatin localization and dynamics in C. elegans.
AB  - During development, the genome undergoes drastic reorganization within the
      nuclear space. To determine tridimensional genome folding, genome-wide techniques
      (damID/Hi-C) can be applied using cell populations, but these have to be
      calibrated using microscopy and single-cell analysis of gene positioning.
      Moreover, the dynamic behavior of chromatin has to be assessed on living samples.
      Combining fast stereotypic development with easy genetics and microscopy, the
      nematode C. elegans has become a model of choice in recent years to study changes
      in nuclear organization during cell fate acquisition. Here we present two
      complementary techniques to evaluate nuclear positioning of genes either by
      fluorescence in situ hybridization in fixed samples or in living worm embryos
      using the GFP-lacI/lacO chromatin-tagging system.

PMID- 23980007
TI  - Measuring the dynamics of chromatin proteins during differentiation.
AB  - Chromatin-protein interactions are important in determining chromosome structure
      and function, thereby regulating gene expression patterns. Most chromatin
      associated proteins bind chromatin in a transient manner, with residence times on
      the order of a few seconds to minutes. This is especially pertinent in mouse
      embryonic stem cells (ESCs), where hyperdynamic binding of chromatin associated
      proteins to chromatin is thought to regulate genome plasticity. In order to
      quantitatively measure binding dynamics of such chromatin proteins in living
      cells, a combination of GFP-fusion proteins and photobleaching-based assays such
      as fluorescence recovery after photobleaching (FRAP) and fluorescence loss in
      photobleaching (FLIP) are advantageous over other existing biochemical assays,
      because they are applied in living cells at a single cell level. In this chapter
      we describe a detailed protocol for performing FRAP and FLIP assays for measuring
      structural chromatin protein dynamics such as Heterochromatin Protein 1 (HP1) and
      linker histone H1 in mouse ESCs and during ESC differentiation.

PMID- 23980008
TI  - Electron spectroscopic tomography of specific chromatin domains.
AB  - The eukaryotic genome is packaged within the nucleus as poly-nucleosome 10 nm
      chromatin fibres. The nucleosome core particle, the fundamental chromatin
      subunit, consists of a DNA molecule wrapped around a histone octamer. Biochemical
      modifications of both the DNA and histone proteins have been characterized that
      influence chromatin structure and function. These modifications include DNA
      methylation, histone variants and posttranslational modifications of the core
      histone protein tails. An outstanding area for investigation in the field of
      nuclear cell biology is the characterization of the functional relation between
      these biochemical modifications and the underlying chromatin structure and
      nuclear sub-compartmentalization. Electron spectroscopic tomography is a high
      resolution microscopy technique that facilitates visualization of individual 10
      nm chromatin fibres in three dimensions. The method, therefore, has a role to
      play in exploring the relationships of the epigenome and nuclear organization.
      Correlating immunofluorescence microscopy with electron spectroscopic tomography
      provides a powerful approach to relate epigenetic marks with high resolution
      chromatin organization. 

PMID- 23980009
TI  - BAC manipulations for making BAC transgene arrays.
AB  - Chromosome tagging using lac or tet operator repeats for in vivo visualization of
      chromosome dynamics has now become a standard methodology used in a range of
      organisms. One variation of this approach has been to build transgene arrays
      creating artificial chromosome blocks to study various aspects of chromatin
      structure, transcription, replication, or DNA repair. Previously, plasmid
      transgenes with or without subsequent gene amplification have been used to build
      these arrays. However, plasmid arrays typically show heterochromatic properties,
      while gene amplification typically results in chromosome instability of the
      amplified regions. To avoid these problems, we are now building transgene arrays
      from large genomic DNA inserts cloned in bacterial artificial chromosomes (BAC).
      These BAC transgenes show transcriptional levels within several fold of
      endogenous genes while also exhibiting targeting to specific nuclear compartments
      similar to the targeting of the endogenous genes. Here we describe Tn5
      transposition and BAC recombineering methods used to retrofit BACs for their use
      in building BAC transgene arrays. This includes insertion of operator repeats and
      selectable markers into these BACs as well as targeted insertion or deletion of
      BAC sequences.

PMID- 23980010
TI  - Spatiotemporal visualization of DNA replication dynamics.
AB  - The ability of cells to copy their DNA allows them to transmit their genetic
      information to their progeny. In such, this central biological process preserves
      the instructions that direct the entire development of a cell. Earlier
      biochemical analysis in vitro and genetic analysis in yeast laid the basis of our
      understanding of the highly conserved mechanism of DNA replication. Recent
      advances on labeling and live-cell microscopy permit now the dissection of this
      fundamental process in vivo within the context of intact cells. In this chapter,
      we describe in detail how to perform multiple DNA replication labeling and
      detection allowing high spatial resolution imaging, as well as how to follow DNA
      replication in living cells allowing high temporal resolution imaging. 

PMID- 23980011
TI  - The dynamics of DNA damage repair and transcription.
AB  - Recent advances have led to several systems to study transcription from defined
      loci in living cells. It has now become possible to address long-standing
      questions regarding the interplay between the processes of DNA damage repair and
      transcription-two disparate processes that can occur on the same stretch of
      chromatin and which both lead to extensive chromatin change. Here we describe the
      development of a system to create enzymatically induced DNA double-strand breaks
      (DSBs) at a site of inducible transcription and methods to study the interplay
      between these processes.

PMID- 23980012
TI  - Fluorescence microscopy-based high-throughput screening for factors involved in
      gene silencing.
AB  - Gene silencing in eukaryotes is a highly controlled process. It involves the
      concerted action of histone and DNA-modifying enzymes as well as transcription
      factors and chromatin-associated proteins. To understand how epigenetic gene
      silencing is regulated, it is important to identify the factors involved in this
      process. Here we describe an assay that allows high-throughput screening for
      factors involved in gene silencing. This assay exploits the susceptibility of the
      viral cytomegalovirus (CMV) promoter to epigenetic silencing in embryonic stem
      cells (ESCs) and uses reporter constructs with an optical readout to determine
      the gene silencing potential of candidate factors. This approach allows to study
      mechanisms and kinetics of gene silencing in living cells and to evaluate the
      role of DNA methyltransferases, histone-modifying enzymes, and other chromatin
      associated factors during gene silencing. 

PMID- 23980013
TI  - Actin as a model for the study of nucleocytoplasmic shuttling and nuclear
      dynamics.
AB  - A great number of molecules are constantly being exchanged between the nucleus
      and the cytoplasm via nuclear pore complexes (NPCs). Importantly, this
      nucleocytoplasmic trafficking is used to transfer information between the two
      compartments, thereby permitting the manipulation of critical nuclear processes
      such as transcription. Constant shuttling of actin is an example of the
      versatility of this regulatory avenue, as this protein has the capability to
      drive the transcriptional activity of certain gene sets as well as influence
      transcription on a global scale. Nuclear import and export are extremely dynamic
      phenomena and require imaging tools capable of rapid sampling rates for proper
      quantitative observation. Here we describe live-cell imaging assays based on
      fluorescence recovery after photobleaching (FRAP) and fluorescence loss in
      photobleaching (FLIP) for monitoring both import and export of fluorescently
      labelled molecules. Our assays are performed with GFP-actin, but the same
      principle is applicable to most proteins shuttling between the nucleus and the
      cytoplasm. Furthermore, these assays may also expose novel qualities of the
      intranuclear dynamics of a protein, which can polymerize or partake in complexes,
      because such behavior is mirrored in the nuclear retention of the protein
      detectable by both import and export assays.

PMID- 23980014
TI  - Isochronal visualization of transcription and proteasomal proteolysis in cell
      culture or in the model organism, Caenorhabditis elegans.
AB  - Investigation of differential gene regulation by protein degradation requires
      analysis of the spatial and temporal association between proteolysis and
      transcription. Here, we describe the isochronal visualization of proteasomal
      proteolysis and transcription in cell culture or in vivo in the model organism
      Caenorhabditis elegans. This includes localization of proteasome-dependent
      proteolysis by fluorescent degradation products of model and endogenous
      substrates of the proteasome in combination with immunolabelling of RNA
      polymerase II and transcription in situ run-on assays.

PMID- 23980015
TI  - Considering discrete protein pools when measuring the dynamics of nuclear
      membrane proteins.
AB  - Measuring dynamics of nuclear proteins is complicated by the fact that many DNA-
      and chromatin-binding proteins have separate nucleoplasmic and nuclear membrane
      pools with distinct mobilities. Moreover, when measuring recoveries in FRAP
      experiments, it is important to be aware that the continuous transport of new
      protein through the nuclear pore complexes means that fluorescence recovery comes
      from both dynamic exchange of protein already within the nucleus and newly
      imported protein. Here we describe fluorescence recovery after photobleaching and
      photoactivation techniques designed to track nuclear membrane proteins and some
      methods we have developed that may help to distinguish these various pools. A
      combination of these approaches with standard FRAP approaches is necessary to
      understand the true dynamics of nuclear proteins. 

PMID- 23980016
TI  - Correlative microscopy of individual cells: sequential application of microscopic
      systems with increasing resolution to study the nuclear landscape.
AB  - The term correlative microscopy denotes the sequential visualization of one and
      the same cell using various microscopic techniques. Correlative microscopy
      provides a unique platform to combine the particular strength of each microscopic
      approach and compensate for its specific limitations. As an example, we report
      results of a correlative microscopic study exploring features of the nuclear
      landscape in HeLa cells. We present a detailed protocol to first investigate
      distinct structural features of a living cell in space and time (4D) using
      spinning disk laser scanning microscopy (SDLSM). Then, after fixation and
      staining of selected structures (e.g., by means of immunodetection), details of
      these structures are explored at increasingly higher resolution using three
      dimensional (3D) confocal laser scanning microscopy (CLSM); super-resolution
      fluorescence microscopy, such as three-dimensional structured illumination
      microscopy (3D-SIM); and transmission electron microscopy (TEM). We discuss
      problems involved in the comparison of images of a given cell nucleus recorded
      with different microscopic approaches, which requires not only a compensation for
      different resolutions but also for various distortions.

PMID- 23980017
TI  - Time-lapse, photoactivation, and photobleaching imaging of nucleolar assembly
      after mitosis.
AB  - Nucleolus assembly starts in telophase with the benefit of building blocks
      passing through mitosis and lasts until cytokinesis generating the two
      independent interphasic cells. Several approaches make it possible to follow the
      dynamics of fluorescent molecules in live cells. Here, three complementary
      approaches are described to measure the dynamics of proteins during nucleolar
      assembly after mitosis: (1) rapid two-color 4-D imaging time-lapse microscopy
      that demonstrates the relative localization and movement of two proteins, (2)
      photoactivation that reveals the directionality of migration from the activated
      area, and (3) fluorescence recovery after photobleaching (FRAP) that measures the
      renewing of proteins in the bleached area. We demonstrate that the order of
      recruitment of the processing machineries into nucleoli results from differential
      sorting of intermediate structures assembled during telophase, the prenucleolar
      bodies. 

PMID- 23980018
TI  - Nucleation of nuclear bodies.
AB  - The nucleus is a complex organelle containing numerous highly dynamic,
      structurally stable domains and bodies, harboring functions that have only begun
      to be defined. However, the molecular mechanisms for their formation are still
      poorly understood. Recently it has been shown that a nuclear body can form de
      novo by self-organization. But little is known regarding what triggers the
      formation of a nuclear body and how subsequent assembly steps are orchestrated.
      Nuclear bodies are frequently associated with specific active gene loci that
      directly contribute to their formation. Both coding and noncoding RNAs can
      initiate the assembly of nuclear bodies with which they are physiologically
      associated. Thus, the formation of nuclear bodies occurs via recruitment and
      consequent accumulation of resident proteins in the nuclear bodies by nucleating
      RNA acting as a seeder. In this chapter I describe how to set up an experimental
      cell system to probe de novo biogenesis of a nuclear body by nucleating RNA and
      nuclear body components tethered on chromatin. 

PMID- 23980019
TI  - Plastic changes following imitation-based speech and language therapy for
      aphasia: a high-density sleep EEG study.
AB  - BACKGROUND OBJECTIVE: measurement of plastic brain changes induced by a novel
      rehabilitative approach is a key requirement for validating its biological
      rationale linking the potential therapeutic gains to the changes in brain
      physiology. OBJECTIVE: Based on an emerging notion linking cortical plastic
      changes to EEG sleep slow-wave activity (SWA) regulation, we aimed to assess the
      acute plastic changes induced by an imitation-based speech therapy in individuals
      with aphasia by comparing sleep SWA changes before and after therapy. METHODS: A
      total of 13 left-hemispheric stroke patients underwent language assessment with
      the Western Aphasia Battery (WAB) before and after 2 consecutive high-density
      (hd) EEG sleep recordings interleaved by a daytime session of imitation-based
      speech therapy (Intensive Mouth Imitation and Talking for Aphasia Therapeutic
      Effects [IMITATE]). This protocol is thought to stimulate bilateral connections
      between the inferior parietal lobule and the ventral premotor areas. RESULTS: A
      single exposure to IMITATE resulted in increases in local EEG SWA during
      subsequent sleep over the same regions predicted by the therapeutic rationale,
      particularly over the right hemisphere (unaffected by the lesion). Furthermore,
      changes in SWA over the left-precentral areas predicted changes in WAB repetition
      scores in our group, supporting the role of perilesional areas in predicting
      positive functional responses. CONCLUSIONS: Our results suggest that SWA changes
      occurring in brain areas activated during imitation-based aphasia therapy may
      reflect the acute plastic changes induced by this intervention. Further testing
      will be needed to evaluate SWA as a non-invasive assessment of changes induced by
      the therapy and as a predictor of positive long-term clinical outcome.

PMID- 23980021
TI  - Autobuttressing of colorectal anastomoses using a mesenteric flap.
AB  - Anastomotic leakage is a common and dreaded complication of colorectal surgery.
      Many different approaches have been tried to attempt to reduce leakage and
      associated morbidity. The concept of reinforcement of an anastomosis by
      buttressing is well established. Techniques described include using sutures,
      native omentum, animal or synthetic material. We report a technique for
      buttressing using a mesenteric flap to envelope the anastomosis. The primary
      rationale is to reduce clinical sequelae of anastomotic leakage by promoting
      local containment, as well as providing a scaffold for healing. Using autologous
      tissue provides a safe, time-efficient and cost-effective buttress without the
      risks of infection or reaction associated with foreign material. A mesenteric
      flap is particularly useful in patients in whom omentum is not available due to
      previous surgery, or to fill the dead space posterior to a low anastomosis within
      the pelvis. 

PMID- 23980020
TI  - The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
      in the treatment of ovarian cancer relapse.
AB  - Nowadays the standard clinical management for advanced epithelial ovarian cancer
      is constituted by primary cytoreductive surgery associated to adjuvant systemic
      chemotherapy. Even if this first-line chemotherapy shows a high rate of complete
      responses, the disease recurrences occur especially in stage-III patients.
      Actually an option for this subset of patients is represented by secondary
      cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy that
      represents a promising therapy, having shown positive results in terms of median
      overall survival, progression free survival and overall survival. However, a much
      more research is still required especially by prospective randomised trials to
      improve outcomes in recurrent ovarian cancer. 

PMID- 23980023
TI  - Effectiveness and complications of anthracycline and taxane in the therapy of
      breast cancer: a meta-analysis.
AB  - OBJECTIVE: To compare the efficacy and safety between anthracycline & taxane and
      anthracycline in the treatment of breast cancer. METHODS: Computer-assisted
      literature search was performed with PubMed, MEDLINE, EMBASE and Cochrane
      Controlled Trials Register (CCTR) to identify pertinent literatures. Software
      RevMan 5.0 was used for statistical analysis. The measurement of interest
      outcomes included severe neurotoxicity, death without breast cancer recurrences,
      leukemia, venous thrombus and severe cardiotoxicity. RESULTS: A total of 10
      randomized controlled trial studies (RCTs) containing 18,198 cases were selected
      in this meta-analysis. Of which, 9,902 cases were treated with anthracycline &
      taxane and 8,296 cases treated with anthracycline alone as control. Anthracycline
      & taxane showed lower risks of incident leukemia (RR = 0.40; 95% CI: 0.18, 0.90),
      venous thrombus (RR = 0.49; 95% CI: 0.29, 0.84) and severe cardiotoxicity (RR =
      0.41, 95%CI: 0.26, 0.66), but higher risks of incident severe neurotoxicity (RR =
      5.97; 95% CI: 1.72, 20.65) and non-recurrent death (RR = 1.79; 95% CI: 1.06,
      3.04), compared to anthracycline alone. CONCLUSION: Clinically important
      differences exist for general safety in favour of the anthracycline & taxane
      rather than anthracycline alone. However, as a result of tumor recurrent rate,
      anthracycline might be superior to anthracycline & taxane. A longer duration of
      follow-up and a larger number of cases are required to better assess the efficacy
      and safety profile of the treatment of breast cancer.

PMID- 23980025
TI  - MITIE: Simultaneous RNA-Seq-based transcript identification and quantification in
      multiple samples.
AB  - MOTIVATION: High-throughput sequencing of mRNA (RNA-Seq) has led to tremendous
      improvements in the detection of expressed genes and reconstruction of RNA
      transcripts. However, the extensive dynamic range of gene expression, technical
      limitations and biases, as well as the observed complexity of the transcriptional
      landscape, pose profound computational challenges for transcriptome
      reconstruction. RESULTS: We present the novel framework MITIE (Mixed Integer
      Transcript IdEntification) for simultaneous transcript reconstruction and
      quantification. We define a likelihood function based on the negative binomial
      distribution, use a regularization approach to select a few transcripts
      collectively explaining the observed read data and show how to find the optimal
      solution using Mixed Integer Programming. MITIE can (i) take advantage of known
      transcripts, (ii) reconstruct and quantify transcripts simultaneously in multiple
      samples, and (iii) resolve the location of multi-mapping reads. It is designed
      for genome- and assembly-based transcriptome reconstruction. We present an
      extensive study based on realistic simulated RNA-Seq data. When compared with
      state-of-the-art approaches, MITIE proves to be significantly more sensitive and
      overall more accurate. Moreover, MITIE yields substantial performance gains when
      used with multiple samples. We applied our system to 38 Drosophila melanogaster
      modENCODE RNA-Seq libraries and estimated the sensitivity of reconstructing
      omitted transcript annotations and the specificity with respect to annotated
      transcripts. Our results corroborate that a well-motivated objective paired with
      appropriate optimization techniques lead to significant improvements over the
      state-of-the-art in transcriptome reconstruction. AVAILABILITY: MITIE is
      implemented in C++ and is available from http://bioweb.me/mitie under the GPL
      license.

PMID- 23980026
TI  - Virtual reality training for surgical trainees in laparoscopic surgery.
AB  - BACKGROUND: Standard 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 virtual reality simulator is an option to
      supplement standard training. Virtual reality training improves the technical
      skills of surgical trainees such as decreased time for suturing and improved
      accuracy. The clinical impact of virtual reality training is not known.
      OBJECTIVES: To assess the benefits (increased surgical proficiency and improved
      patient outcomes) and harms (potentially worse patient outcomes) of supplementary
      virtual reality training of surgical trainees with limited laparoscopic
      experience. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE and Science
      Citation Index Expanded until July 2012. SELECTION CRITERIA: We included all
      randomised clinical trials comparing virtual reality training versus other forms
      of training including box-trainer training, no training, or standard laparoscopic
      training in surgical trainees with little laparoscopic experience. We also
      planned to include trials comparing different methods of virtual reality
      training. We included only trials that assessed the outcomes in people undergoing
      laparoscopic surgery. 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 analysis. For each
      outcome we calculated the mean difference (MD) or standardised mean difference
      (SMD) with 95% confidence intervals based on intention-to-treat analysis. MAIN
      RESULTS: We included eight trials covering 109 surgical trainees with limited
      laparoscopic experience. Of the eight trials, six compared virtual reality versus
      no supplementary training. One trial compared virtual reality training versus box
      trainer training and versus no supplementary training, and one trial compared
      virtual reality training versus box-trainer training. There were no trials that
      compared different forms of virtual reality training. All the trials were at high
      risk of bias. Operating time and operative performance were the only outcomes
      reported in the trials. The remaining outcomes such as mortality, morbidity,
      quality of life (the primary outcomes of this review) and hospital stay (a
      secondary outcome) were not reported. Virtual reality training versus no
      supplementary training: The operating time was significantly shorter in the
      virtual reality group than in the no supplementary training group (3 trials; 49
      participants; MD -11.76 minutes; 95% CI -15.23 to -8.30). Two trials that could
      not be included in the meta-analysis also showed a reduction in operating time
      (statistically significant in one trial). The numerical values for operating time
      were not reported in these two trials. The operative performance was
      significantly better in the virtual reality group than the no supplementary
      training group using the fixed-effect model (2 trials; 33 participants; SMD 1.65;
      95% CI 0.72 to 2.58). The results became non-significant when the random-effects
      model was used (2 trials; 33 participants; SMD 2.14; 95% CI -1.29 to 5.57). One
      trial could not be included in the meta-analysis as it did not report the
      numerical values. The authors stated that the operative performance of virtual
      reality group was significantly better than the control group. Virtual reality
      training versus box-trainer training: The only trial that reported operating time
      did not report the numerical values. In this trial, the operating time in the
      virtual reality group was significantly shorter than in the box-trainer group. Of
      the two trials that reported operative performance, only one trial reported the
      numerical values. The operative performance was significantly better in the
      virtual reality group than in the box-trainer group (1 trial; 19 participants;
      SMD 1.46; 95% CI 0.42 to 2.50). In the other trial that did not report the
      numerical values, the authors stated that the operative performance in the
      virtual reality group was significantly better than the box-trainer group.
      AUTHORS' CONCLUSIONS: Virtual reality training appears to decrease the operating
      time and improve the operative performance of surgical trainees with limited
      laparoscopic experience when compared with no training or with box-trainer
      training. However, the impact of this decreased operating time and improvement in
      operative performance on patients and healthcare funders in terms of improved
      outcomes or decreased costs is not known. Further well-designed trials at low
      risk of bias and random errors are necessary. Such trials should assess the
      impact of virtual reality training on clinical outcomes.

PMID- 23980024
TI  - Identification of transcription factor binding sites from ChIP-seq data at high
      resolution.
AB  - MOTIVATION: Chromatin immunoprecipitation coupled to next-generation sequencing
      (ChIP-seq) is widely used to study the in vivo binding sites of transcription
      factors (TFs) and their regulatory targets. Recent improvements to ChIP-seq, such
      as increased resolution, promise deeper insights into transcriptional regulation,
      yet require novel computational tools to fully leverage their advantages.
      RESULTS: To this aim, we have developed peakzilla, which can identify closely
      spaced TF binding sites at high resolution (i.e. resolves individual binding
      sites even if spaced closely), as we demonstrate using semisynthetic datasets,
      performing ChIP-seq for the TF Twist in Drosophila embryos with different
      experimental fragment sizes, and analyzing ChIP-exo datasets. We show that the
      increased resolution reached by peakzilla is highly relevant, as closely spaced
      Twist binding sites are strongly enriched in transcriptional enhancers,
      suggesting a signature to discriminate functional from abundant non-functional or
      neutral TF binding. Peakzilla is easy to use, as it estimates all the necessary
      parameters from the data and is freely available. AVAILABILITY AND
      IMPLEMENTATION: The peakzilla program is available from
      https://github.com/steinmann/peakzilla or
      http://www.starklab.org/data/peakzilla/. CONTACT: stark@starklab.org.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 23980027
TI  - Crystal structure of RuvC resolvase in complex with Holliday junction substrate.
AB  - The key intermediate in genetic recombination is the Holliday junction (HJ), a
      four-way DNA structure. At the end of recombination, HJs are cleaved by specific
      nucleases called resolvases. In Gram-negative bacteria, this cleavage is
      performed by RuvC, a dimeric endonuclease that belongs to the retroviral
      integrase superfamily. Here, we report the first crystal structure of RuvC in
      complex with a synthetic HJ solved at 3.75 A resolution. The junction in the
      complex is in an unfolded 2-fold symmetrical conformation, in which the four arms
      point toward the vertices of a tetrahedron. The two scissile phosphates are
      located one nucleotide from the strand exchange point, and RuvC approaches them
      from the minor groove side. The key protein-DNA contacts observed in the
      structure were verified using a thiol-based site-specific cross-linking approach.
      Compared with known complex structures of the phage resolvases endonuclease I and
      endonuclease VII, the RuvC structure exhibits striking differences in the mode of
      substrate binding and location of the cleavage site. 

PMID- 23980028
TI  - Development of a universal radioactive DNA methyltransferase inhibition test for
      high-throughput screening and mechanistic studies.
AB  - DNA methylation is an important epigenetic mark in eukaryotes, and aberrant
      pattern of this modification is involved in numerous diseases such as cancers.
      Interestingly, DNA methylation is reversible and thus is considered a promising
      therapeutic target. Therefore, there is a need for identifying new small
      inhibitors of C5 DNA methyltransferases (DNMTs). Despite the development of
      numerous in vitro DNMT assays, there is a lack of reliable tests suitable for
      high-throughput screening, which can also give insights into inhibitor mechanisms
      of action. We developed a new test based on scintillation proximity assay meeting
      these requirements. After optimizing our assay on human DNMT1 and calibrating it
      with two known inhibitors, we carried out S-Adenosyl-l-Methionine and DNA
      competition studies on three inhibitors and were able to determine each mechanism
      of action. Finally, we showed that our test was applicable to 3 other
      methyltransferases sources: human DNMT3A, bacterial M.SssI and cellular extracts
      as well. 

PMID- 23980029
TI  - Conformational transitions in human translin enable nucleic acid binding.
AB  - Translin is a highly conserved RNA- and DNA-binding protein that plays essential
      roles in eukaryotic cells. Human translin functions as an octamer, but in the
      octameric crystallographic structure, the residues responsible for nucleic acid
      binding are not accessible. Moreover, electron microscopy data reveal very
      different octameric configurations. Consequently, the functional assembly and the
      mechanism of nucleic acid binding by the protein remain unclear. Here, we present
      an integrative study combining small-angle X-ray scattering (SAXS), site-directed
      mutagenesis, biochemical analysis and computational techniques to address these
      questions. Our data indicate a significant conformational heterogeneity for
      translin in solution, formed by a lesser-populated compact octameric state
      resembling the previously solved X-ray structure, and a highly populated open
      octameric state that had not been previously identified. On the other hand, our
      SAXS data and computational analyses of translin in complex with the RNA
      oligonucleotide (GU)12 show that the internal cavity found in the octameric
      assemblies can accommodate different nucleic acid conformations. According to
      this model, the nucleic acid binding residues become accessible for binding,
      which facilitates the entrance of the nucleic acids into the cavity. Our data
      thus provide a structural basis for the functions that translin performs in RNA
      metabolism and transport. 

PMID- 23980030
TI  - A novel factor Iss10 regulates Mmi1-mediated selective elimination of meiotic
      transcripts.
AB  - A number of meiosis-specific transcripts are selectively eliminated during the
      mitotic cell cycle in fission yeast. Mmi1, an RNA-binding protein, plays a
      crucial role in this selective elimination. Mmi1 recognizes a specific region,
      namely, the determinant of selective removal (DSR) on meiotic transcripts and
      induces nuclear exosome-mediated elimination. During meiosis, Mmi1 is sequestered
      by a chromosome-associated dot structure, Mei2 dot, allowing meiosis-specific
      transcripts to be stably expressed. Red1, a zinc-finger protein, is also known to
      participate in the Mmi1/DSR elimination system, although its molecular function
      has remained elusive. To uncover the detailed molecular mechanisms underlying the
      Mmi1/DSR elimination system, we sought to identify factors that interact
      genetically with Mmi1. Here, we show that one of the identified factors, Iss10,
      is involved in the Mmi1/DSR system by regulating the interaction between Mmi1 and
      Red1. In cells lacking Iss10, association of Red1 with Mmi1 is severely impaired,
      and target transcripts of Mmi1 are ectopically expressed in the mitotic cycle.
      During meiosis, Iss10 is downregulated, resulting in dissociation of Red1 from
      Mmi1 and subsequent suppression of Mmi1 activity. 

PMID- 23980032
TI  - The efficacy of manual joint mobilisation/manipulation in treatment of lateral
      ankle sprains: a systematic review.
AB  - BACKGROUND: Lateral ankle sprains are common and can have detrimental
      consequences to the athlete. Joint mobilisation/manipulation may limit these
      outcomes. OBJECTIVE: Systematically summarise the effectiveness of manual joint
      techniques in treatment of lateral ankle sprains. METHODS: This review employed
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines. A computer-assisted literature search of MEDLINE, CINHAL, EMBASE,
      OVID and Physiotherapy Evidence Database (PEDro) (January 1966 to March 2013) was
      used with the following keywords alone and in combination 'ankle', 'sprain',
      'injuries', 'lateral', 'manual therapy', and 'joint mobilisation'. The
      methodological quality of individual studies was assessed using the PEDro scale.
      RESULTS: After screening of titles, abstracts and full articles, eight articles
      were kept for examination. Three articles achieved a score of 10 of 11 total
      points; one achieved a score of 9; two articles scored 8; one article scored a 7
      and the remaining article scored a 5. Three articles examined joint techniques
      for acute sprains and the remainder examined subacute/chronic ankle sprains.
      Outcome measures included were pain level, ankle range of motion, swelling,
      functional score, stabilometry and gait parameters. The majority of the articles
      only assessed these outcome measures immediately after treatment. No detrimental
      effects from the joint techniques were revealed in any of the studies reviewed.
      CONCLUSIONS: For acute ankle sprains, manual joint mobilisation diminished pain
      and increased dorsiflexion range of motion. For treatment of subacute/chronic
      lateral ankle sprains, these techniques improved ankle range-of-motion, decreased
      pain and improved function.

PMID- 23980033
TI  - Celebrating 20 years of the international Cochrane Collaboration.
AB  - In 2013 the international Cochrane Collaboration is celebrating the 20th
      anniversary of its foundation with a series of events, publications, and videos.
      The "Cochrane Corner" has been a regular feature of Otolaryngology-Head and Neck
      Surgery for several years, but for those unfamiliar with the work of Cochrane we
      provide some background about our organization. 

PMID- 23980031
TI  - Directed evolution of the TALE N-terminal domain for recognition of all 5' bases.
AB  - Transcription activator-like effector (TALE) proteins can be designed to bind
      virtually any DNA sequence. General guidelines for design of TALE DNA-binding
      domains suggest that the 5'-most base of the DNA sequence bound by the TALE (the
      N0 base) should be a thymine. We quantified the N0 requirement by analysis of the
      activities of TALE transcription factors (TALE-TF), TALE recombinases (TALE-R)
      and TALE nucleases (TALENs) with each DNA base at this position. In the absence
      of a 5' T, we observed decreases in TALE activity up to >1000-fold in TALE-TF
      activity, up to 100-fold in TALE-R activity and up to 10-fold reduction in TALEN
      activity compared with target sequences containing a 5' T. To develop TALE
      architectures that recognize all possible N0 bases, we used structure-guided
      library design coupled with TALE-R activity selections to evolve novel TALE N
      terminal domains to accommodate any N0 base. A G-selective domain and broadly
      reactive domains were isolated and characterized. The engineered TALE domains
      selected in the TALE-R format demonstrated modularity and were active in TALE-TF
      and TALEN architectures. Evolved N-terminal domains provide effective and
      unconstrained TALE-based targeting of any DNA sequence as TALE binding proteins
      and designer enzymes. 

PMID- 23980035
TI  - [Interpretations of practice parameters for the management of rectal cancer(2013
      released by American Society of Colon and Rectal Surgeons)].

PMID- 23980034
TI  - Factors affecting postural instability in Meniere's disease.
AB  - OBJECTIVE: To assess the influence of factors that can affect the postural
      instability of Meniere's disease (MD) patients. STUDY DESIGN: Case-control study.
      SETTING: Outpatient clinic in a university hospital. SUBJECTS AND METHODS: Fifty
      four definite MD patients and 66 controls were included. Two-legged stance tasks
      were performed in 4 conditions: eyes open with and without foam rubber and eyes
      closed with and without foam rubber. We examined 6 variables: the velocity of
      movement of the center of pressure (COP), the envelopment area traced by the
      movement of the COP, Romberg's ratio of velocity and area, and the foam ratios of
      velocity and area. For patients, stepwise multiple regression analyses were
      performed to explore the relationship between the 6 variables and the following
      independent variables: gender, age, the presence of abnormal caloric and/or
      cervical vestibular evoked myogenic potential (cVEMP) responses, the time elapsed
      since the last vertigo attack, and the disease duration. RESULTS: The presence of
      MD had a significantly positive relationship with all 6 of the variables (P <
      .05). The presence of abnormal caloric and/or cVEMP responses had a significantly
      positive relationship with Romberg's ratio of velocity (P < .05) and area (P <
      .01). The shorter time interval from last vertigo attack to measurement had a
      significantly positive relationship with the foam ratio of area (P < .01).
      CONCLUSION: MD patients show poor postural performance, which is affected by the
      existence of their peripheral vestibular function and the shorter time interval
      from last vertigo attack to measurement.

PMID- 23980036
TI  - [Standardized diagnosis and treatment of colorectal liver metastasis from the
      perspective of evidence-based medicine].
AB  - Colorectal cancer is one of the most common malignancies in human, and colorectal
      liver metastasis (CLM) is one of the most common leading causes of death in these
      patients. In recent years, along with the update of diagnosis and treatment
      concept and advancement of operative technique, more and more patients with CLM
      get surgical treatment opportunities and the outcomes are improved. In clinical
      practice of CLM, depending on evidence-based medicine, standardized diagnosis and
      treatment is particularly important, which includes diagnosis and treatment by
      multidisciplinary team, accurate evaluation of the resectability of CLM,
      standardized surgical resection and essential comprehensive treatment. 

PMID- 23980037
TI  - [Disputes about surgical treatment of colorectal liver metastasis].
AB  - As the most common metastasis in colorectal cancer, liver metastasis is the
      primary cause of treatment failure. Resection plays a dominant role in
      multidisciplinary treatment of colorectal liver metastases. However, this
      surgical field is still filled with disputes and challenges. Literature on liver
      metastasis of colorectal cancer were reviewed and clinical trials were collected.
      Different opinions were analyzed according to clinical evidence and personal
      experience. There are many disputes about surgical treatment of colorectal liver
      metastases, including incomplete staging system, inconsistent criteria of
      potential resectability, neoadjuvant chemotherapy for resectable liver
      metastases, adjuvant chemotherapy regimen after radical resection, and treatment
      of asymptomatic primary lesion in patients with unresectable liver metastasis. 

PMID- 23980039
TI  - [Anatomic basis of function-preserving operation for low rectal cancer].
AB  - Total mesorectal excision (TME) is being established as the gold standard for
      rectal cancer surgery, however sexual and urinary dysfunction is an established
      risk after TME. By cadaver dissections, we clarify the correct surgical plane for
      TME and further determine the relation between the surgical plane and pelvic
      autonomic nerves. It must be noted that the pelvic plexus can be divided into 2
      categories: aggregated shape and diffused shape. The latter is in tight contact
      with visceral fascia, which seems to be inseparable from each other by sharp
      dissection. Therefore, it is necessary to study the function of different units
      in pelvic plexus.

PMID- 23980038
TI  - [Consideration of therapy for colorectal cancer with synchronous unresectable
      liver metastasis].
AB  - A variety of managements, including systemic and local chemotherapy,
      radiofrequency ablation and others, are used after multidisciplinary team
      discussion to improve the survival of patients with unresectable liver
      metastasis, and to enlarge the cohort of patients who can be managed with
      curative intent. Patients should be divided into different clinical groups
      according to characteristics of the patient and tumor, and then receive different
      treatments. For the patients who may be converted to be resectable after
      chemotherapy, we should choose efficient convertible chemotherapy with short
      courses to get the best response rate. For KRAS wild-type patients, cetuximab
      combined with FOLFOX/FOLFIRI, in which 5-fluorouracil is continuously infused, is
      recommended. In addition, resection of the primary tumor is recommended at the
      right time for asymptomatic patients with unresectable liver metastases. There is
      no consensus on the preferred treatment modality for systemic and local
      therapies. 

PMID- 23980040
TI  - [Assessment value of preoperative neutrophil-lymphocyte ratio for the prognosis
      of patients with colorectal cancer after radical operation].
AB  - OBJECTIVE: To assess the value of preoperative neutrophil-lymphocyte ratio (NLR)
      for prognosis in patients with colorectal cancer after radical operation.
      METHODS: Clinical data of 140 patients with colorectal cancer undergoing radical
      operation in the Department of General Surgery of General Hospital of PLA from
      July 2005 to July 2011 were analyzed retrospectively. According to preoperative
      NLR, patients were divided into the low NLR group (NLR<5, n=105) and the high NLR
      group (NLR>=5, n=35). The overall 5-year survival rates of two groups were
      compared and the independent risk factors were examined by univariate analysis
      and Cox model. RESULTS: The overall 5-year survival rates of the low and high NLR
      groups were 74.8% and 54.7% respectively with significant difference (P=0.03).
      Univariate analysis revealed depth of tumor, lymph nodes metastasis, TMN stage
      and NLR were associated with survival (P<0.05, P<0.01). Cox model showed that NLR
      was independent risk factor of prognosis (RR=1.068, 95%CI:1.009-1.129, P=0.02).
      CONCLUSION: Preoperative NLR>=5 predicts poorer prognosis of colorectal cancer
      patients.

PMID- 23980041
TI  - [Application of laparoscopic transanal coloanal anastomosis in sphincter
      preserving surgery for low rectal cancer].
AB  - OBJECTIVE: To evaluate the efficacy of laparoscopic transanal coloanal
      anastomosis (modified Parks procedure) in sphincter-preserving surgery for low
      rectal carcinoma. METHODS: Clinical data of 65 low rectal cancer patients
      undergoing laparoscopic modified Parks procedure from March 2009 to April 2012 in
      our department were reviewed retrospectively. Fecal continence, urination and
      sexual function were evaluated. RESULTS: All the patients were followed up from 6
      to 38 months after operation. Anastomotic leakage was found in 2 cases,
      anastomotic stricture in 3 cases, hepatic metastasis in 1 case. No local
      recurrence occurred. The ratio of satisfactory defecation function was 61.5%
      (40/65) in six months, 84.2% (48/57) in 1 year and 88.9% (40/45) in 2 years
      respectively. Urinary dysfunction was found in 7 patients (10.8%). Among 36 male
      patients, 7 (19.4%) presented erectile dysfunction and 10 (27.8%) ejaculation
      dysfunction. Among 29 female patients, sexual life of 19 (65.5%) was
      satisfactory. CONCLUSION: Laparoscopic modified Parks procedure in sphincter
      preserving surgery for low rectal cancer can increase the ratio of sphincter
      preserving, and improve the functional outcomes of defecation, sex and urination.

PMID- 23980042
TI  - [Clinical significance of tumor budding detection in stage II colon cancer].
AB  - OBJECTIVE: To investigate the association of tumor budding with recurrence and
      survival of patients with stage II colon cancer, in order to identify patients
      with high-risk recurrence who may benefit from adjuvant therapy. METHODS:
      Clinical data of 112 stage II colon cancer patients in Guangzhou Red Cross
      Hospital between 1998 and 2007 were analyzed retrospectively. The degree of tumor
      budding was assessed by two observers and classified according to the number of
      tumor buds in the area with the greatest budding intensity on HE stain slides, as
      high-grade budding (>=10, n=30) and low-grade budding (<=9, n=82). Progression
      free and cancer-specific survival were analyzed using the Kaplan-Meier method and
      Cox regression. RESULTS: All the patients were followed up and the median follow
      up was 78 months. The 5-year progression-free survival rates for patients with
      high-grade and low-grade budding were 65.3% and 90.7% respectively (P=0.008). The
      5-year cancer-specific survival rates were 72.1% and 93.8% respectively
      (P=0.001). Cox regression analysis demonstrated tumor budding was an independent
      predictor of disease progression (RR=4.572, 95%CI:2.218-11.746, P=0.002) and
      cancer-related death (RR=4.116, 95%CI:1.657-10.384, P=0.012). CONCLUSION: Tumor
      budding is a strong prognostic index for adverse outcome in stage II colon cancer
      patients,which may serve as a prognostic marker to identify patients with high
      risk of recurrence who may benefit from adjuvant therapy.

PMID- 23980043
TI  - [Effect of early oral enteral nutrition on clinical outcomes after colorectal
      cancer surgery].
AB  - OBJECTIVE: To investigate the effect of early oral feeding with enteral nutrition
      after surgery on clinical outcomes in patients with colorectal cancer. METHODS:
      Forty-eight patients with colorectal cancer undergoing elective operation between
      January 2012 and May 2012 were randomly divided into study group (n=24) and
      control group (n=24). Patients in the group were given small amount of water
      several times and enteral nutrition early after surgery. Patients in the control
      group received conventional postoperative care protocol. Nutritional status,
      immune function, time of flatus, postoperative hospital stay, medical cost and
      incidence of complications between the two groups were compared. RESULTS: As
      compared to the control group, nutritional status and immune function in the
      study group were significantly better (P<0.05). In the study group, time to
      flatus [(54.3+/-11.9) h vs. (65.7+/-10.0) h, P<0.05] and postoperative hospital
      stay [(5.4+/-1.1) d vs. (7.1+/-1.4) d, P<0.05] were significantly shorter, and
      medical cost [(36.3+/-6.4) thousand RMB vs. (42.8+/-4.3) thousand RMB, P<0.05]
      was significantly less as compared with the control group. No difference of the
      complication incidence was found [12.5% (3/24) vs. 16.7% (4/24), P>0.05].
      CONCLUSION: Early oral feeding with enteral nutrition after surgery can improve
      the nutritional status and immune function, and accelerate the recovery of
      patients with colorectal cancer.

PMID- 23980044
TI  - [Effect of intermittent pneumatic compression on coagulation function and deep
      venous hemodynamics of lower limbs after rectal cancer resection].
AB  - OBJECTIVE: To investigate the effects of intermittent pneumatic compression (IPC)
      on coagulation function, deep venous hemodynamics and prevention of deep venous
      thrombosis (DVT) of lower limbs in patients after rectal cancer resection.
      METHODS: A total of 120 patients undergoing rectal cancer resection were randomly
      divided into non-IPC group (control group, n=60) and IPC group (n=60). The
      control group received routine treatment after resection and the IPC group
      received IPC based on the routine treatments. Prothrombin time (PT), activated
      partial thromboplastin time (APTT), fibrinogen (FIB), international normalized
      ratio (INR) and volume of D-dimer (D-D) were detected before operation and 1-, 3
      , 5- and 7-day after operation. Meanwhile, blood flow velocity and caliber of
      external iliac vein, femoral vein and popliteal vein were examined by color
      Doppler ultrasound, then the average blood flow velocity and blood flow volume
      were calculated. RESULTS: Incidence of lower limb DVT was 13.3% (8/60) and 1.7%
      (1/60) in control group and IPC group respectively with significant difference
      (P<0.05). The differences in PT, APTT and INR were not significant (P>0.05) at 1
      day after operation as compared to the preoperative level, while FIB and D-D both
      increased (P<0.05), all presented no significant difference among the two groups
      (P>0.05). PT shortened gradually (P<0.05), APTT and INR did not change
      significantly (P>0.05), FIB and D-D increased gradually (P<0.05), and no
      significant differences were found between the two groups at the same time point
      (all P>0.05). All the above parameters in the control group were significantly
      lower than those in IPC group (all P<0.05). CONCLUSIONS: IPC can improve
      hemodynamics indexes of deep veins of lower limb in patients after rectal cancer
      operation, and prevent the lower limb DVT. IPC is a safe, simple and convenient
      physical therapy.

PMID- 23980045
TI  - [Follow-up analysis of health-related quality of life research after radical
      surgery for rectal cancer].
AB  - OBJECTIVE: To explore how to improve follow-up rate and follow-up quality in
      studies related to quality of life. METHODS: A retrospective cross-sectional
      study was performed in patients with rectal cancer who underwent primary surgery
      at the Gastrointestinal Surgery Department, The First Affiliated Hospital, Sun
      Yat-sen University from August 2002 to February 2011 using the European
      Organization for Research and Treatment of Cancer QLQ-C30 and CR-38
      questionnaires. The influence factors of follow-up rate and reasons for missing
      sex-related items were analyzed. RESULTS: A total of 438 questionnaires were
      issued. Two hundred and eighty-five responses were received and the follow-up
      rate was 65.1%. Two hundred and sixty-two patients returned the questionnaires by
      mail. Responders and non-responders did not differ by sociodemographic and
      clinical characteristics including sex, age, postoperative time, complication,
      clinical stage and stoma. Significant differences were found when comparing the
      missing sex-related items grouped by sex, age, education and working status.
      CONCLUSIONS: Follow-up mode of mail supplemented by interview is suitable for
      current reality in China in studies on quality of life. Targeted methods should
      be adopted when investigating the different patient groups to improve follow-up
      rate of studies on quality of life and sexual function survey.

PMID- 23980046
TI  - [Meta-analysis of laparoscopic versus open total mesorectal excision for middle
      and low rectal cancer].
AB  - OBJECTIVE: To evaluate the efficacy of laparoscopic total mesorectal excision
      (laparoscopic TME) versus open total mesorectal excision (open TME) in the
      treatment of middle and low rectal cancer using meta-analysis. METHOD: From 1991
      to 2012, the Chinese and English articles of randomized controlled trails (RTCs)
      about laparoscopic TME versus open TME in the treatment of middle and low rectal
      cancer were collected, and a meta-analysis was performed with RevMan 5.1
      software. RESULTS: Eight RCTs including 863 patients with middle and low rectal
      cancer (428 cases in laparoscopic TME group, 435 cases in open TME group) were
      enrolled in the meta-analysis. Laparoscopic TME was associated with significantly
      less intraoperative blood loss (P<0.01), earlier to pass first flatus (P<0.01),
      shorter hospital stay (P<0.05), less postoperative incision infections (P<0.01)
      and postoperative bleeding (P<0.05) compared to open TME. There were no
      significant differences between laparoscopic TME and open TME groups in operative
      time, number of resected lymph nodes, anastomotic leak, ileus and pelvic abscess
      (all P>0.05). CONCLUSIONS: As compared to open TME, laparoscopic TME has similar
      efficacy in terms of lymph nodes harvest, and it can promote postoperative
      recovery, and reduce incision infection and postoperative bleeding.

PMID- 23980047
TI  - [Association of epithermal growth factor receptor expression and its downstream
      gene mutation status with radiosensitivity of colorectal carcinoma cell lines in
      vitro].
AB  - OBJECTIVE: To investigate the effect of epithermal growth factor receptor (EGFR)
      expression and K-ras, B-raf and PIK3CA mutation status on the radiosensitivity of
      human colorectal carcinoma (CRC) cell lines in vitro. METHODS: Real-time RT-PCR
      was used to measure EGFR mRNA expression in nine human CRC cell lines, and K-ras,
      B-raf and PIK3CA mutation status of each CRC cell line was also identified
      respectively. After treatment with irradiation at graded dose, the cell viability
      was measured by clonogenic survival assay. The rate of cell apoptosis and cell
      cycle distribution were tested by flow cytometry. The cell morphology was
      observed with hoechst 33258 staining to analyze the correlation between EGFR mRNA
      expression and radiosensitivity of CRC cell lines. RESULTS: A positive
      correlation between EGFR mRNA expression and survival fraction of 2 Gy(SF2) was
      observed (r=0.717, P=0.030). Association was also identified between the mutation
      status of PIK3CA and radiosensitivity (t=2.401, P=0.047), while mutation status
      of K-ras and B-raf was not associated with radiosensitivity. At 48-hour after
      exposing to irradiation, the apoptosis rate of radiosensitive cell line (HCT116)
      was significantly increased in a dose-dependent manner (P<0.05), while the
      apoptosis rate of radioresistant cell line (HT29) was significantly increased
      only when radiation dose increased to 6 Gy. The ratio of G0/G1 phase was reduced
      significantly with the increase of radiation dose in radiosensitive cell line
      (HCT116, P<0.05), while this trend was not observed in radioresistant cell line
      (HT29, P>0.05). CONCLUSIONS: Over-expression of EGFR mRNA is correlated to
      radioresistance of human CRC cell lines, and mutation status of PIK3CA is closely
      related with radiosensitivity of CRC cells. The inhibition of apoptosis and G0/G1
      arrest may induce the radioresistance of CRC cell lines.

PMID- 23980048
TI  - [Effect of human colon carcinoma-associated fibroblasts on biological behavior of
      colon carcinoma Lovo cells].
AB  - OBJECTIVE: To investigate the effects of human colon carcinoma-associated
      fibroblasts (CAFs) on proliferation, adhesion, migration and invasion of colon
      carcinoma Lovo cells. METHODS: The co-culture models among colon CAFs, NFs and
      Lovo cell were established by conditioned medium (CM) of human colon CAFs and
      colon normal fibroblasts (NFs). Lovo cells in the blank control group was treated
      with serum-free culture medium. The effects of human colon CAFs on proliferation,
      adhesion, migration and invasion of colon carcinoma Lovo cells were detected by
      cell proliferation assay, adhesion assay, migration assay and Transwell invasion
      assay. RESULTS: After co-culture with colon CAFs, the absorbance (A) value of
      Lovo cells was (0.667+/-0.059) in 48 h and (0.709+/-0.030) in 72 h. The A value
      of Lovo cells adhesion to fibronectin was (0.588+/-0.067). The cell mobility
      rates were (35.2+/-8.7)% in 12 h and (64.6+/-7.1)% in 24 h. The number of
      invasive cell was (56.2+/-4.8). All the above parameters were increased compared
      with those in the blank control group and NFs group (all P<0.01). CONCLUSION:
      Human colon CAFs can promote the proliferation, adhesion, migration and invasion
      of colon carcinoma Lovo cells.

PMID- 23980049
TI  - [Risk factors associated with postoperative complications of D2 radical resection
      for local advanced gastric cancer].
AB  - OBJECTIVE: To evaluate the risk factors of postoperative complications following
      D2 radical resection for advanced gastric cancer. METHODS: From June 2004 to May
      2011, 483 patients with local advanced gastric cancer who underwent radical
      gastrectomy with D2 lymph node dissection were enrolled in the study, including
      132 patients of LAG (27.3%) and 351 patients of open procedure (72.7%).
      Clinicopathological data and postoperative complications were reviewed
      retrospectively. Postoperative complications were classified into overall and
      severe complications according to Clavien-Dindo Classification. Multivariate
      logistic model was used to identify risk factors of postoperative complications.
      RESULTS: The overall incidence of postoperative overall and severe complications
      and mortality were 12.4% (60/483), 2.5% (12/483) and 0.2% (1/483), respectively.
      Univariate analysis showed that no significant differences were found in overall
      and severe complications between the two surgical approaches (13.6% vs. 12.0%,
      P=0.620; 3.0% vs. 2.3%, P=0.743). Furthermore, multivariate analysis showed that
      age >=60 years, preoperative comorbidity and intraoperative blood loss >300 ml
      were independent risk factors associated with overall postoperative
      complications. Remarkably, intraoperative blood loss >300 ml was also an
      independent risk factor for severe postoperative complications. CONCLUSIONS: LAG
      with D2 lymph node dissection for local advanced gastric cancer is technically
      feasible and safe. However, the elderly, preoperative comorbidity and increased
      intraoperative blood loss are associated with elevated risk of complications.
      Decreased intraoperative bleeding may reduce the potential postoperative
      complications.

PMID- 23980050
TI  - [Clinicopathological features and prognosis of chronic gastric ulcer with early
      canceration].
AB  - OBJECTIVE: To evaluate the clinicopathological features and prognosis of chronic
      gastric ulcer with early canceration in order to provide useful information for
      diagnosis and treatment strategies. METHODS: A retrospective review of clinical
      data and prognosis from 43 patients of chronic gastric ulcer with early
      canceration from 2003 to 2010 was conducted. These data were compared with those
      with primary intra-mucosa gastric cancer (type I and II 275 cases, type III 68
      cases). RESULTS: In 43 cases of chronic gastric ulcer with early canceration, 30
      cases (69.8%) were male, 22 cases (51.2%) were younger than 60 years old. Lesions
      located in the body or antrum of the stomach in 39 cases (90.7%), were less than
      2 cm in 26 cases (60.5%), were undifferentiated type in 23 cases (53.5%), and
      developed lymph node metastasis in 4 cases (9.3%). Lesions of 4 cases of chronic
      gastric ulcer with early canceration located in the upper third of the stomach,
      while those of type III primary intra-mucosal gastric cancer all located in the
      lower two thirds, and the difference was statistically significant (P<0.01).
      Compared to type III and type I and II primary intra-mucosal gastric cancer,
      chronic gastric ulcer with early canceration did not differ in
      clinicopathological characteristics such as histological type, vascular or
      lymphatic invasion, and lymph nodes metastasis (all P>0.05). The median follow-up
      time was 57 months (range 16 to 98 months). The 5-year overall survival was 95.3%
      in chronic gastric ulcer with early canceration group, similar to that of type I,
      II (97.4%) or type III (94.5%) primary intra-mucosal gastric cancer group
      (P>0.05). CONCLUSIONS: The clinicopathological features of chronic gastric ulcer
      with early canceration are similar to those of primary intra-mucosal gastric
      cancer. The prognosis is promising for those patients undergoing surgical
      treatment.

PMID- 23980051
TI  - [Animal experimental study of biodegradable magnesium alloy stapler for
      gastrointestinal anastomosis].
AB  - OBJECTIVE: To explore the safety and feasibility of biodegradable magnesium alloy
      stapler based on the result of animal experimental study for gastrointestinal
      anastomosis. METHODS: Sixteen beagle dogs were equally and randomly divided into
      experimental (magnesium alloy) group and control (titanium alloy) group. A
      gastrojejunal and a colonic anastomosis were performed in each beagle dog. The
      anastomosis time, postoperative complications, body weight, blasting pressure of
      anastomosis and serum glutamic pyruvic transaminase, glutamic oxaloacetic
      transaminase, creatinine, blood urea nitrogen, and serum magnesium were compared
      between the two groups. The healing of anastomosis and degradation of magnesium
      alloy were observed. The histopathological features of heart, liver, spleen and
      kidney were examined in the two groups. RESULTS: There were no significant
      differences in anastomosis time, body weight, postoperative complications,
      anastomotic bursting pressure between the two groups. The anastomosis was healed
      well, and no dramatic inflammatory cell infiltration was observed. Magnesium
      alloy could be degraded completely in the animal body within 90 days. There were
      no significant differences in serum glutamic pyruvic transaminase, glutamic
      oxaloacetic transaminase, creatinine, blood urea nitrogen and serum magnesium
      between the two groups. Histopathological examination showed that the degradation
      of magnesium alloy did not harm the important organs (liver, kidney, heart, brain
      and spleen). CONCLUSIONS: Magnesium alloy stapler is safe and feasible for
      gastrointestinal anastomosis in beagle dogs. The degradation of magnesium alloy
      does not harm the healing of anastomosis and other important organs. Magnesium
      alloy stapler may be a candidate of biodegradable and safe material of stapler
      for gastrointestinal anastomosis in human.

PMID- 23980052
TI  - [Alterations of Cajal cells in the colon of slow transit constipation rats].
AB  - OBJECTIVE: To investigate the association of expression of c-kit (marker of
      interstitial cells of Cajal, ICC) in colon with slow transit constipation (STC)
      in rats. METHODS: Slow transit constipation (STC) rat model was induced by
      intragastric administration of compound diphenoxylate. Western blotting was used
      to measure the expression of c-kit in colon of STC rats (model group) and normal
      rats (control group). Gray scale ratio of c-kit to beta-actin was used as the
      relative quantity of c-kit. RESULTS: Fecal quantity per day of STC group was
      (1.3+/-0.7) g/100 g, significantly lower than that in normal rats [(1.6+/-0.9)
      g/100 g, t=10.798, P<0.05]. In model rats, the time of discharge of the first
      black fecal was (461.6+/-150.8) min, significantly longer than that in normal
      rats [(351.3+/-119.9) min, t=2.291, P<0.05]. Western blotting revealed that the
      average values of gray scale ratio of c-kit in proximal colon were 0.277+/-0.077
      and 0.576+/-0.081 (t=10.719, P<0.05), in distal colon were 0.280+/-0.075 and
      0.571+/-0.079 (t=10.700, P<0.05) in model group and control group respectively.
      CONCLUSION: Down-regulation of c-kit expression in proximal colon and distal
      colon is associated to the pathogenesis of slow transit constipation in rats.

PMID- 23980053
TI  - [Research progression in markers associated with colorectal liver metastasis].
AB  - Colorectal cancer (CRC) is the third common malignant tumor worldwide and the
      second cause of cancer-related death. Liver metastasis is the main cause of
      mortality in colorectal cancer. Exploration of the mechanism and the processes of
      liver metastasis, and therapeutic intervention are important to improve the
      overall survival and the quality of life of patients with colorectal cancer.
      Biomarkers has been one of the hot spots in the study of colorectal cancer. More
      and more biomarkers are being found and warrant further study.

PMID- 23980054
TI  - [Research progression in tumor-infiltration lymphocytic cells in colorectal
      cancer].
AB  - With the development of tumor immunology research, it has been recognized that
      the anti-tumor immune system function is better to predict the prognosis.
      Relationship between the tumor-infiltrating lymphocytes (TIL) and colorectal
      cancer has become one of the hot topics in research. Here we summarize the latest
      studies about the relationship between the TIL and clinicopathological factors,
      prognosis and microsatellite instability (MSI).

PMID- 23980055
TI  - MicroRNAs transfected into granulosa cells may regulate oocyte meiotic competence
      during in vitro maturation of mouse follicles.
AB  - STUDY QUESTION: Do microRNAs (miRNAs) in granulosa cells (GCs) affect oocyte
      maturation during ovarian follicle development? SUMMARY ANSWER: Sophisticated
      regulation by miRNAs in ovarian GCs may improve oocyte maturation efficiency
      during ovarian follicle development. WHAT IS KNOWN ALREADY: The meiotic
      competence of oocytes depends on the follicle's potential to undergo appropriate
      maturation and is an important factor in infertility therapies such as IVF. The
      exact function of the GCs during follicular development remains unknown. STUDY
      DESIGN, SIZE, DURATION: After in vitro maturation (IVM) and ovulation induction
      of isolated ovarian pre-antral follicles from 12-day-old female C57BL6 mice (n =
      40), miRNA expression in the GCs was compared according to the maturity of the
      oocyte (metaphase I (MI) versus metaphase II (MII)). The miRNAs, which showed
      notable different expression, were modulated by transfection during IVM of
      follicles. MATERIALS, SETTING, METHODS: miRNA expression and candidate target
      gene expression in GCs of isolated murine ovarian pre-antral follicles were
      evaluated by real-time PCR after IVM. miR mimics and -inhibitors for selected
      miRNAs were transfected into the in vitro-maturated follicles, and ovulation,
      oocyte maturation and fertilization rates were compared. Candidate target gene
      expressions in GC were evaluated by quantitative PCR and immunohistochemistry
      using confocal microscopy. MAIN RESULTS AND THE ROLE OF CHANCE: The relative
      expression of mmu-let-7b (0.78 +/- 0.10, P = 0.016), mmu-let-7c (0.78 +/- 0.12, P
      = 0.029), mmu-miR-27a (0.57 +/- 0.18, P = 0.016) and mmu-miR-322 (0.59 +/- 0.14,
      P = 0.008) was significantly lower in the GCs of follicles containing MII oocytes
      compared with those of MI oocytes. Transfection with a mmu-miR-27a-mimic sequence
      decreased the oocyte maturation rate compared with that for the control (9.4
      versus 18.9%, P = 0.042), and transfection with mmu-let-7c-, mmu-miR-27a- and mmu
      miR-322-inhibitor sequences increased the oocyte maturation rate by 1.5- to 2.0
      folds compared with that for the control (40.6, 31.6, and 30.5%versus 18.9%, P <
      0.001, P = 0.013, P = 0.021, respectively). The expression of IGFBP-2 was higher
      in GCs of MII than in the GCs of MI, and higher in miR-inhibitor transfection
      groups than in miR-mimic transfection groups and controls. LIMITATIONS, REASONS
      FOR CAUTION: An in vitro model was used in lieu of an in vivo model because of
      the ease of performing miRNA transfection in cell culture. However, studies have
      shown similarities and differences in in vivo versus in vitro cultured follicles.
      The findings of the present study need to be confirmed using in vivo maturation
      models and extended to evaluate developmental competence. WIDER IMPLICATIONS OF
      THE FINDINGS: Our findings suggest that sophisticated miRNA regulation in GCs may
      improve oocyte maturation efficiency during ovarian follicle development. STUDY
      FUNDING/COMPETING INTEREST(S): This work was supported by a grant from the Korean
      Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea
      (A111539). None of the authors has any conflicts of interest to declare.

PMID- 23980056
TI  - The effect of letrozole with misoprostol for medical termination of pregnancy on
      the expression of steroid receptors in the placenta.
AB  - STUDY QUESTION: What is the effect of letrozole on the expression of steroid
      receptors in the placentae in cases of termination of pregnancies? SUMMARY
      ANSWER: The expression of estrogen receptor-alpha (ERalpha) and progesterone
      receptor (PR) transcripts, as well as ERalpha protein, in placentae was
      suppressed by letrozole pretreatment in second trimester termination of
      pregnancy. WHAT IS KNOWN ALREADY: There have been no data in the literature on
      the effect of letrozole in termination of human pregnancies. STUDY DESIGN, SIZE,
      DURATION: This study is part of a clinical randomized trial in which 50 subjects
      were recruited and 44 placentae were collected. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: Women (n = 50) requesting second trimester abortion between 12 and 20
      gestational weeks were randomized to receive either letrozole or placebo
      pretreatment for 3 days before administration of vaginal misoprostol. Placentae
      were collected from both groups of women after the abortion. Total RNA from the
      frozen placenta samples was extracted and subjected to real-time RT-PCR analysis
      of ERalpha and estrogen receptor-beta (ERbeta), PR and glucocorticoid receptor
      (GR) transcripts. Immunohistochemical studies of ERalpha, ERbeta, PR and GR
      expression, as well as Ki67 and PCNA staining for proliferation, were performed.
      TUNEL assays were performed to determine the extent of apoptosis. MAIN RESULTS
      AND THE ROLE OF CHANCE: Real-time RT-PCR demonstrated that the median ERalpha
      {3.900 [95% confidence interval (CI): -0.643-8.443] in the letrozole group versus
      4.714 (95% CI: 1.776-7.652) in the control group; P = 0.005} and the median PR
      [0.701 (95% CI: 0.333-1.069) in the letrozole group versus 1.774 (95% CI: 1.07
      2.478) in the control group; P = 0.003] were significantly lower in the letrozole
      group compared with the control group. Furthermore, ERalpha protein levels, in
      both syncytiotrophoblasts and cytotrophoblasts but not in villous stromal cells,
      were significantly reduced [H-score of 113 (95% CI: 103-119) in the letrozole
      group versus 217 (95% CI: 214-290) in the control group, in syncytiotrophoblasts;
      100 (95% CI: 98-105) in the letrozole group versus 210 (95% CI: 200-286) in the
      control group, in cytotrophoblasts; P = 0.004], while the expression levels of
      ERbeta, PR, GR, PCNA, Ki67 and TUNEL were not significantly different between the
      two groups. LIMITATIONS, REASONS FOR CAUTION: Only the placentae from the second
      trimester termination of pregnancy were collected in this study. Information from
      first trimester terminations is still lacking. WIDER IMPLICATIONS OF THE
      FINDINGS: The results shed some light on the mechanism of action of letrozole
      pretreatment in termination of pregnancies. STUDY FUNDING/COMPETING INTEREST(S):
      This study was funded by the GRF/RGC and CRCG grants of the University of Hong
      Kong. TRIAL REGISTRATION NUMBER: HKClinicalTrials.com with trial number HKCTR
      695.

PMID- 23980057
TI  - External validation of models and simple scoring systems to predict miscarriage
      in intrauterine pregnancies of uncertain viability.
AB  - STUDY QUESTION: Does a logistic regression model and scoring system to predict
      viability of an intrauterine pregnancy of uncertain viability (PUV) perform as
      well in an independent patient group as the original patient group? SUMMARY
      ANSWER: The model and scoring system showed good performance on external
      validation confirming their value for the prediction of miscarriage/viability in
      PUV patients up to 11-14 weeks of gestation. WHAT IS KNOWN ALREADY: Several
      individual ultrasound and demographic factors have been described as predictors
      for miscarriage. A logistic regression model and simple scoring system using
      basic clinical and ultrasound features, such as maternal age, bleeding score,
      mean gestational sac diameter (MSD) and presence or absence of yolk sac, have
      been developed to allow patient-specific prediction of viability of PUV beyond
      the first trimester. STUDY DESIGN, SIZE, DURATION: Prospective observational
      external validation cohort study in two inner city early pregnancy assessment
      units over a period of 18 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: All
      consecutive women with a PUV were recruited. Ultrasound (mean sac diameter and
      presence of yolk sac) and demographic variables (maternal age, bleeding score and
      gestational age) were noted. The outcome measure was first trimester (11-14 week)
      viability. Women with unknown first trimester outcome were excluded. Receiver
      operating characteristic (ROC) curves and calibration plots were constructed.
      Test performance was compared with the original development data set. A new model
      and scoring system, which did not include gestational age, was built and
      evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 575 women who were
      recruited, first trimester outcome was known for 89.2% (n = 513). The model could
      only be validated in 400 patients, due to missing values in model variables and
      outcome. The model predicted viability with an area under the ROC curve (AUC) of
      0.845 [95% confidence interval (CI), 0.806-0.884] compared with 0.774 (95% CI,
      0.701-0.848) in the original study. The AUC for the scoring system was 0.832 (95%
      CI, 0.792-0.872) compared with 0.771 (95% CI, 0.698-0.844) from the original
      study data set. The new model and the scoring system, excluding gestational age,
      could be evaluated on 503 patients and resulted in an AUC of 0.801 (95% CI, 0.765
      0.841) for the model and 0.773 (95% CI, 0.733-0.812) for the scoring system.
      LIMITATIONS, REASONS FOR CAUTION: Approximately 22% of patients could not be
      validated due to missing variables and for 11% of patients the first trimester
      outcome was unknown. WIDER IMPLICATIONS OF THE FINDINGS: Both the model and the
      scoring system showed excellent performance on external validation confirming
      their generalizability and utility in prediction of viability beyond the first
      trimester in clinical practice. An advantage of the mathematical models original
      Mo and new Mn and scoring systems original SSo and new SSn is that they can
      provide women with an individualized probability of the viability of their
      pregnancy using only demographic information, symptoms and TVS findings.
      Furthermore, the risk of miscarriage can be given immediately following
      examination. STUDY FUNDING/COMPETING INTEREST(S): T.B. is supported by the
      Imperial Healthcare NHS Trust NIHR Biomedical Research Centre. This research is
      supported by Research Council KUL GOA MaNet, iMinds 2012, Belgian Federal Science
      Policy Office IUAP P719. VVB is a postdoctoral fellow of the Research Foundation 
      Flanders (FWO). There are no conflicts of interest.

PMID- 23980058
TI  - Dehydroepiandrosterone induces ovarian and uterine hyperfibrosis in female rats.
AB  - STUDY QUESTION: Do dehydroepiandrosterone (DHEA)-treated rats with polycystic
      ovary syndrome (PCOS) demonstrate a high level of fibrosis in ovarian and uterine
      tissues? SUMMARY ANSWER: DHEA induces ovarian and uterine hyperfibrosis in rats,
      probably involving a transforming growth factor-beta (TGF-beta)-dependent
      mechanism. WHAT IS KNOWN ALREADY: Chronic inflammation is the typical cause of
      fibrosis and is involved in the pathophysiological process of PCOS. Patients with
      PCOS are reported to have a higher serum level of TGF-beta, a well-characterized
      key pro-fibrotic factor. Fibrillin-3, a protein capable of interacting with TGF
      beta, has been reported to be partially responsible for the fetal origin of PCOS.
      STUDY DESIGN, SIZE, DURATION: Female Sprague-Dawley rats were treated with a
      vehicle control or DHEA for 35 days, with subsequent analyses of changes in
      morphology and gene expression in ovarian and uterine tissues. Rescue groups
      treated with metformin or simvastatin and their corresponding controls were also
      analyzed. A total of 80 rats were included. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: The PCOS model was induced by daily administration of DHEA s.c. to 3
      week-old female rats, and the rescue groups were injected daily with either
      metformin or simvastatin in addition to DHEA. Serum steroid hormone levels were
      measured by enzyme-linked immunosorbent assay. Samples were stained with
      hematoxylin and eosin for histological morphology, and Sirius Red and
      immunohistochemistry for revealing collagens. The expression of fibrosis-related
      genes was analyzed both at mRNA (real-time RT-PCR) and protein (western blot)
      levels. MAIN RESULTS AND THE ROLE OF CHANCE: DHEA-induced rats with PCOS
      exhibited significantly higher levels of fibrosis (collagen IV) in both ovarian
      and uterine tissues. In ovarian tissue, the expression of connective tissue
      growth factor (CTGF) increased following DHEA treatment at both mRNA and protein
      levels (P < 0.05, P < 0.001 versus controls, respectively). Similar results
      versus controls were obtained at a protein level for TGF-beta (P < 0.01) and mRNA
      level for fibronectin (P < 0.05) and angiotensin-II (P < 0.05). Likewise, in
      uterine tissue, the protein levels of both CTGF and TGF-beta were higher than
      controls following DHEA treatment (P < 0.05). Treatment with either metformin or
      simvastatin attenuated the fibrosis progression induced by DHEA exposure, as
      evidenced by a reduction of TGF-beta, plus CTGF or not, in both ovarian and
      uterine tissues. LIMITATIONS, REASONS FOR CAUTION: The particular mechanism
      involved in the DHEA-induced fibrosis was not fully revealed. WIDER IMPLICATIONS
      OF THE FINDINGS: Ovarian and uterine hyperfibrosis may occur in patients with
      PCOS and result in anovulation or other PCOS-related phenotypes. Anti-fibrotic
      therapy, for example metformin treatment, may be beneficial for patients with
      PCOS. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the
      National Natural Science Foundation of China (81170541) and the Natural Basic
      Research Program of China (973 program 2010CB945103). The authors declare no
      conflicts of interest.

PMID- 23980059
TI  - A Mitraclip affaire: early detachment and iatrogenic interatrial defect.

PMID- 23980060
TI  - Integrated reverse left and right ventricular remodelling after MitraClip
      implantation in functional mitral regurgitation: an echocardiographic study.
AB  - AIMS: The aim of the present study was to investigate the changes of left and
      right ventricular (RV) dimensions and function after MitraClip implantation in
      high-risk surgical patients with severe functional mitral regurgitation (MR).
      METHODS AND RESULTS: Study population included 35 patients with functional MR.
      All the patients underwent clinical and echocardiographic evaluation at baseline,
      before discharge and at 6-month follow-up. The mean age was 75 years (63-81),
      65.7% (n = 23) was male with a mean logistic EuroSCORE of 20%. Percutaneous
      mitral valve repair acronym (PMVR) resulted in significantly reduced MR and
      improved in New York Heart Association functional class. Echocardiography
      revealed improvement in left ventricular (LV) size and function since discharge
      with further improvement at 6 months. During the follow-up, a significant
      improvement in RV function was also observed by the baseline values. At baseline,
      before discharge and 6 months, respectively, the tricuspid annulus plane systolic
      excursion (TAPSE) was 16.8 +/- 3.9, 18.7 +/- 3.4, and 19.3 +/- 4.5 mm (P =
      0.001); the systolic pulmonary artery pressure (SPAP) was 50.1 +/- 6.8, 41.2 +/-
      6.8, and 38.1 +/- 6.8 mmHg (P < 0.0001); and the systolic velocity at the
      tricuspid annular (RV-Sm) was 8.8 +/- 2.9, 10.4 +/- 3.5, and 17.7 +/- 3.1 cm (P <
      0.0001). CONCLUSION: MitraClip implantation induces a significant reverse
      remodelling of LV, with reduction in both diastolic and systolic LV volumes and
      an increase in the cardiac index. The concomitant reduction in LV filling
      pressure, obtained after MitraClip implantation, reflects nearly immediately on
      the haemodynamics of the right sections. In fact, since discharge, we observed
      both a reverse remodelling of the right sections, with a significant reduction in
      SPAP, and a significant increase in longitudinal RV systolic function as shown by
      the increase in TAPSE and RV-Sm.

PMID- 23980061
TI  - MitraClip and right ventricular function: hopes and doubts.

PMID- 23980062
TI  - Patch abscess after a closure of an atrial septal defect.

PMID- 23980063
TI  - Neutrophils mediate antibody-induced antitumor effects in mice.
AB  - Tumor engraftment followed by monoclonal antibody (mAb) therapy targeting tumor
      antigens represents a gold standard for assessing the efficiency of mAbs to
      eliminate tumor cells. Mouse models have demonstrated that receptors for the Fc
      portion of immunoglobulin G (FcgammaRs) are critical determinants of mAb
      therapeutic efficacy, but the FcgammaR-expressing cell populations responsible
      remain elusive. We show that neutrophils are responsible for mAb-induced therapy
      of both subcutaneous syngeneic melanoma and human breast cancer xenografts. mAb
      induced tumor reduction, abolished in neutropenic mice, could be restored in
      FcgammaR-deficient hosts upon transfer of FcgammaR+ neutrophils or upon human
      FcgammaRIIA/CD32A transgenic expression. Finally, conditional knockout mice
      unable to perform FcgammaR-mediated activation and phagocytosis specifically in
      neutrophils were resistant to mAb-induced therapy. Our work suggests that
      neutrophils are necessary and sufficient for mAb-induced therapy of subcutaneous
      tumors, and represent a new and critical focal point for optimizing mAb-induced
      immunotherapies that will impact on human cancer treatment.

PMID- 23980064
TI  - The integrin coactivator Kindlin-3 is not required for lymphocyte diapedesis.
AB  - Kindlin-3 is an integrin-binding focal adhesion adaptor absent in patients with
      leukocyte and platelet adhesion deficiency syndrome and is critical for firm
      integrin-dependent leukocyte adhesion. The role of this adaptor in leukocyte
      diapedesis has never been investigated. In the present study, the functions of
      Kindlin-3 in this process were investigated in effector T lymphocytes trafficking
      to various lymphoid and nonlymphoid tissues. In vitro, Kindlin-3-deficient T
      cells displayed severely impaired lymphocyte function antigen-1-dependent
      lymphocyte adhesion but partially conserved very late antigen-4 adhesiveness. In
      vivo, the number of adoptively transferred Kindlin-3-deficient T effectors was
      dramatically elevated in the circulating pool compared with normal effectors, and
      the Kindlin-3 mutant effectors failed to enter inflamed skin lesions. The
      frequency of Kindlin-3-deficient T effectors arrested on vessel walls within
      inflamed skin-draining lymph nodes was also reduced. Strikingly, however, Kindlin
      3-deficient effector T cells accumulated inside these vessels at significantly
      higher numbers than their wild-type lymphocyte counterparts and successfully
      extravasated into inflamed lymph nodes. Nevertheless, on entering these organs,
      the interstitial motility of these lymphocytes was impaired. This is the first in
      vivo demonstration that Kindlin-3-stabilized integrin adhesions, although
      essential for lymphocyte arrest on blood vessels and interstitial motility, are
      not obligatory for leukocyte diapedesis. 

PMID- 23980066
TI  - Development of acute megakaryoblastic leukemia in Down syndrome is associated
      with sequential epigenetic changes.
AB  - Acute megakaryoblastic leukemia (AMKL) is more frequently observed in Down
      syndrome (DS) patients, in whom it is often preceded by a transient
      myeloproliferative disorder (TMD). The development of DS-TMD and DS-AMKL requires
      not only the presence of the trisomy 21 but also that of GATA1 mutations. Despite
      extensive studies into the genetics of DS-AMKL, the importance of epigenetic
      deregulation in this disease has been unexplored. We performed DNA methylation
      profiling at different stages of development of DS-AMKL and analyzed the dynamics
      of the epigenetic program. Early genome-wide DNA methylation changes can be
      detected in trisomy 21 fetal liver mononuclear cells, prior to the acquisition of
      GATA1 mutations. These early changes are characterized by marked loss of DNA
      methylation at genes associated with developmental disorders, including those
      affecting the cardiovascular, neurological, and endocrine systems. This is
      followed by a second wave of changes detected in DS-TMD and DS-AMKL,
      characterized by gains of methylation. This new wave of hypermethylation targets
      a distinct set of genes involved in hematopoiesis and regulation of cell growth
      and proliferation. These findings indicate that the final epigenetic landscape of
      DS-AMKL is the result of sequential and opposing changes in DNA methylation
      occurring at specific times in the disease development. 

PMID- 23980068
TI  - Choosing a model to predict hospital admission: an observational study of new
      variants of predictive models for case finding.
AB  - OBJECTIVES: To test the performance of new variants of models to identify people
      at risk of an emergency hospital admission. We compared (1) the impact of using
      alternative data sources (hospital inpatient, A&E, outpatient and general
      practitioner (GP) electronic medical records) (2) the effects of local
      calibration on the performance of the models and (3) the choice of population
      denominators. DESIGN: Multivariate logistic regressions using person-level data
      adding each data set sequentially to test value of additional variables and
      denominators. SETTING: 5 Primary Care Trusts within England. PARTICIPANTS: 1 836
      099 people aged 18-95 registered with GPs on 31 July 2009. MAIN OUTCOME MEASURES:
      Models to predict hospital admission and readmission were compared in terms of
      the positive predictive value and sensitivity for various risk strata and with
      the receiver operating curve C statistic. RESULTS: The addition of each data set
      showed moderate improvement in the number of patients identified with little or
      no loss of positive predictive value. However, even with inclusion of GP
      electronic medical record information, the algorithms identified only a small
      number of patients with no emergency hospital admissions in the previous 2 years.
      The model pooled across all sites performed almost as well as the models
      calibrated to local data from just one site. Using population denominators from
      GP registers led to better case finding. CONCLUSIONS: These models provide a
      basis for wider application in the National Health Service. Each of the models
      examined produces reasonably robust performance and offers some predictive value.
      The addition of more complex data adds some value, but we were unable to conclude
      that pooled models performed less well than those in individual sites. Choices
      about model should be linked to the intervention design. Characteristics of
      patients identified by the algorithms provide useful information in the
      design/costing of intervention strategies to improve care coordination/outcomes
      for these patients.

PMID- 23980067
TI  - mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to
      sites of inflammation.
AB  - Mesenchymal stem cells (MSCs) are promising candidates for cell-based therapy to
      treat several diseases and are compelling to consider as vehicles for delivery of
      biological agents. However, MSCs appear to act through a seemingly limited "hit
      and-run" mode to quickly exert their therapeutic impact, mediated by several
      mechanisms, including a potent immunomodulatory secretome. Furthermore, MSC
      immunomodulatory properties are highly variable and the secretome composition
      following infusion is uncertain. To determine whether a transiently controlled
      antiinflammatory MSC secretome could be achieved at target sites of inflammation,
      we harnessed mRNA transfection to generate MSCs that simultaneously express
      functional rolling machinery (P-selectin glycoprotein ligand-1 [PSGL-1] and
      Sialyl-Lewis(x) [SLeX]) to rapidly target inflamed tissues and that express the
      potent immunosuppressive cytokine interleukin-10 (IL-10), which is not inherently
      produced by MSCs. Indeed, triple-transfected PSGL-1/SLeX/IL-10 MSCs transiently
      increased levels of IL-10 in the inflamed ear and showed a superior
      antiinflammatory effect in vivo, significantly reducing local inflammation
      following systemic administration. This was dependent on rapid localization of
      MSCs to the inflamed site. Overall, this study demonstrates that despite the
      rapid clearance of MSCs in vivo, engineered MSCs can be harnessed via a "hit-and
      run" action for the targeted delivery of potent immunomodulatory factors to treat
      distant sites of inflammation. 

PMID- 23980069
TI  - Sex-related differences in hypertension: seek and ye shall find.

PMID- 23980065
TI  - Diagnosis and treatment of primary myelodysplastic syndromes in adults:
      recommendations from the European LeukemiaNet.
AB  - Within the myelodysplastic syndrome (MDS) work package of the European
      LeukemiaNet, an Expert Panel was selected according to the framework elements of
      the National Institutes of Health Consensus Development Program. A systematic
      review of the literature was performed that included indexed original papers,
      indexed reviews and educational papers, and abstracts of conference proceedings.
      Guidelines were developed on the basis of a list of patient- and therapy-oriented
      questions, and recommendations were formulated and ranked according to the
      supporting level of evidence. MDSs should be classified according to the 2008
      World Health Organization criteria. An accurate risk assessment requires the
      evaluation of not only disease-related factors but also of those related to
      extrahematologic comorbidity. The assessment of individual risk enables the
      identification of fit patients with a poor prognosis who are candidates for up
      front intensive treatments, primarily allogeneic stem cell transplantation. A
      high proportion of MDS patients are not eligible for potentially curative
      treatment because of advanced age and/or clinically relevant comorbidities and
      poor performance status. In these patients, the therapeutic intervention is aimed
      at preventing cytopenia-related morbidity and preserving quality of life. A
      number of new agents are being developed for which the available evidence is not
      sufficient to recommend routine use. The inclusion of patients into prospective
      clinical trials is strongly recommended. 

PMID- 23980070
TI  - Orally active epoxyeicosatrienoic acid analog attenuates kidney injury in
      hypertensive Dahl salt-sensitive rat.
AB  - Salt-sensitive hypertension leads to kidney injury. The Dahl salt-sensitive
      hypertensive rat (Dahl SS) is a model of salt-sensitive hypertension and
      progressive kidney injury. The current set of experimental studies evaluated the
      kidney protective potential of a novel epoxyeicosatrienoic acid analog (EET-B) in
      Dahl SS hypertension. Dahl SS rats receiving high-salt diet were treated with EET
      B (10 mg/kg per day) or vehicle in drinking water for 14 days. Urine, plasma, and
      tissue samples were collected at the end of the treatment protocol to assess
      kidney injury, oxidative stress, inflammation, and endoplasmic reticulum stress.
      EET-B treatment in Dahl SS rats markedly reduced urinary albumin and nephrin
      excretion by 60% to 75% along with 30% to 60% reductions in glomerular injury,
      intratubular cast formation, and kidney fibrosis without affecting blood
      pressure. In Dahl SS rats, EET-B treatment further caused marked reduction in
      oxidative stress with 25% to 30% decrease in kidney malondialdehyde content along
      with 42% increase of nitrate/nitrite and a 40% reduction of 8-isoprostane. EET-B
      treatment reduced urinary monocyte chemoattractant protein-1 by 50% along with a
      40% reduction in macrophage infiltration in the kidney. Treatment with EET-B
      markedly reduced renal endoplasmic reticulum stress in Dahl SS rats with
      reduction in the kidney mRNA expressions and immunoreactivity of glucose
      regulatory protein 78 and C/EBP homologous protein. In summary, these
      experimental findings reveal that EET-B provides kidney protection in Dahl SS
      rats by reducing oxidative stress, inflammation, and endoplasmic reticulum
      stress, and this protection was independent of reducing blood pressure. 

PMID- 23980071
TI  - There is more to salt than just a pinch of sodium.

PMID- 23980072
TI  - Hypertension: a harbinger of stroke and dementia.

PMID- 23980073
TI  - Serum chloride is an independent predictor of mortality in hypertensive patients.
AB  - Chloride (Cl-) is the major extracellular anion in the body, accompanying sodium
      (Na+), and is primarily derived from dietary sources. Data suggest that increased
      dietary Cl- intake increases blood pressure, yet paradoxically, higher serum Cl-
      appears associated with lower mortality and cardiovascular risk. This implies
      that serum Cl- also reflects risk pathways independent of blood pressure, serum
      Na+, and bicarbonate (HCO3-). We analyzed 12,968 hypertensive individuals
      followed up for 35 years, using Cox proportional hazards model to test whether
      baseline serum Cl- was an independent predictor of mortality. To distinguish the
      effect of Cl- from Na+ and HCO3-, we adjusted for these electrolytes and also
      performed the analysis stratified by Na+ /HCO3- and Cl- levels. Generalized
      estimating equation was used to determine the effect of baseline Cl- on follow-up
      blood pressure. The total time at risk was 19,7101 person-years. The lowest
      quintile of serum Cl- (<100 mEq/L) was associated with a 20% higher mortality
      (all-cause, cardiovascular and noncardiovascular) compared with the remainder of
      the subjects. A 1 mEq/L increase in serum Cl- was associated with a 1.5% (hazard
      ratio, 0.985; 95% confidence interval, 0.98-0.99) reduction in all-cause
      mortality, after adjustment for baseline confounding variables and Na+, K+ , and
      HCO3- levels. The group with Na+ > 135 and Cl- > 100 had the best survival, and
      compared with this group, the Na+ >135 and Cl- <100 group had significantly
      higher mortality (hazard ratio, 1.21; 95% confidence interval, 1.11-1.31). Low,
      not high Serum Cl- (<100 mEq/L), is associated with greater mortality risk
      independent of obvious confounders. Further studies are needed to elucidate the
      relation between Cl- and risk.

PMID- 23980074
TI  - Increased salt sensitivity of ambulatory blood pressure in women with a history
      of severe preeclampsia.
AB  - Cardiovascular diseases are the principal cause of death in women in developed
      countries and are importantly promoted by hypertension. The salt sensitivity of
      blood pressure (BP) is considered as an important cardiovascular risk factor at
      any BP level. Preeclampsia is a hypertensive disorder of pregnancy that arises as
      a risk factor for cardiovascular diseases. This study measured the salt
      sensitivity of BP in women with a severe preeclampsia compared with women with no
      pregnancy hypertensive complications. Forty premenopausal women were recruited 10
      years after delivery in a case-control study. Salt sensitivity was defined as an
      increase of >4 mm Hg in 24-hour ambulatory BP on a high-sodium diet. The
      ambulatory BP response to salt was significantly increased in women with a
      history of preeclampsia compared with that of controls. The mean (95% confidence
      interval) daytime systolic/diastolic BP increased significantly from 115 (109
      118)/79 (76-82) mm Hg on low-salt diet to 123 (116-130)/80 (76-84) on a high-salt
      diet in women with preeclampsia, but not in the control group (from 111 [104
      119]/77 [72-82] to 111 [106-116]/75 [72-79], respectively, P<0.05). The sodium
      sensitivity index (SSI=Deltamean arterial pressure/Deltaurinary Na
      excretion*1000) was 51.2 (19.1-66.2) in women with preeclampsia and 6.6 (5.8
      18.1) mm Hg/mol per day in controls (P=0.015). The nocturnal dip was blunted on a
      high-salt diet in women with preeclampsia. Our study shows that women who have
      developed preeclampsia are salt sensitive before their menopause, a finding that
      may contribute to their increased cardiovascular risk. Women with a history of
      severe preeclampsia should be targeted at an early stage for preventive measures
      of cardiovascular diseases. 

PMID- 23980075
TI  - Dietary energy balance modulation of Kras- and Ink4a/Arf+/--driven pancreatic
      cancer: the role of insulin-like growth factor-I.
AB  - New molecular targets and intervention strategies for breaking the obesity
      pancreatic cancer link are urgently needed. Using relevant spontaneous and
      orthotopically transplanted murine models of pancreatic cancer, we tested the
      hypothesis that dietary energy balance modulation impacts pancreatic cancer
      development and progression through an insulin-like growth factor (IGF)-I
      dependent mechanism. In LSL-Kras(G12D)/Pdx-1-Cre/Ink4a/Arf(lox/+) mice, calorie
      restriction versus overweight- or obesity-inducing diet regimens decreased serum
      IGF-I, tumoral Akt/mTOR signaling, pancreatic desmoplasia, and progression to
      pancreatic ductal adenocarcinoma (PDAC), and increased pancreatic tumor-free
      survival. Serum IGF-I, Akt/mTOR signaling, and orthotopically transplanted PDAC
      growth were decreased in liver-specific IGF-I-deficient mice (vs. wild-type
      mice), and rescued with IGF-I infusion. Thus, dietary energy balance modulation
      impacts spontaneous pancreatic tumorigenesis induced by mutant Kras and Ink4a
      deficiency, the most common genetic alterations in human pancreatic cancer.
      Furthermore, IGF-I and components of its downstream signaling pathway are
      promising mechanistic targets for breaking the obesity-pancreatic cancer link.

PMID- 23980076
TI  - Reply to R.L. Olin et al.

PMID- 23980077
TI  - Randomized, multicenter, open-label study of oxaliplatin plus
      fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients
      with advanced hepatocellular carcinoma from Asia.
AB  - PURPOSE: To determine whether FOLFOX4 (infusional fluorouracil, leucovorin, and
      oxaliplatin) administered as palliative chemotherapy to patients with advanced
      hepatocellular carcinoma (HCC) provides a survival benefit and efficacy versus
      doxorubicin. PATIENTS AND METHODS: This multicenter, open-label, randomized,
      phase III study in mainland China, Taiwan, Korea, and Thailand involved 371
      patients age 18 to 75 years who had locally advanced or metastatic HCC and were
      ineligible for curative resection or local treatment. They were randomly assigned
      at a ratio of one to one to receive either FOLFOX4 (n = 184) or doxorubicin (n =
      187). The primary end point was overall survival (OS); secondary end points
      included progression-free survival (PFS), response rate (RR) by RECIST (version
      1.0), and safety. RESULTS: At the prespecified final analysis, median OS was 6.40
      months with FOLFOX4 (95% CI, 5.30 to 7.03) and 4.97 months with doxorubicin (95%
      CI, 4.23 to 6.03; P = .07; hazard ratio [HR], 0.80; 95% CI, 0.63 to 1.02). Median
      PFS was 2.93 months with FOLFOX4 (95% CI, 2.43 to 3.53), and 1.77 months with
      doxorubicin (95% CI, 1.63 to 2.30; P < .001; HR, 0.62; 95% CI, 0.49 to 0.79). RR
      was 8.15% with FOLFOX4 and 2.67% with doxorubicin (P = .02). On continued follow
      up, the trend toward increased OS with FOLFOX4 was maintained (P = .04; HR, 0.79;
      95% CI, 0.63 to 0.99). Toxicity was consistent with previous experiences with
      FOLFOX4; proportions of grade 3 to 4 adverse events were similar between
      treatments. CONCLUSION: Although the study did not meet its primary end point,
      the trend toward improved OS with FOLFOX4, along with increased PFS and RR,
      suggests that this regimen may confer some benefit to Asian patients, but an OS
      benefit cannot be concluded from these data.

PMID- 23980079
TI  - Epidermal growth factor receptor inhibition in mutation-positive non-small-cell
      lung cancer: is afatinib better or simply newer?

PMID- 23980078
TI  - Processing speed, attention, and working memory after treatment for
      medulloblastoma: an international, prospective, and longitudinal study.
AB  - PURPOSE: The current study prospectively examined processing speed (PS), broad
      attention (BA), and working memory (WM) ability of patients diagnosed with
      medulloblastoma over a 5-year period. PATIENTS AND METHODS: The study included
      126 patients, ages 3 to 21 years at diagnosis, enrolled onto a collaborative
      protocol for medulloblastoma. Patients were treated with postsurgical risk
      adapted craniospinal irradiation (n = 36 high risk [HR]; n = 90 average risk)
      followed by four cycles of high-dose chemotherapy with stem-cell support.
      Patients completed 509 neuropsychological evaluations using the Woodcock-Johnson
      Tests of Cognitive Abilities Third Edition (median of three observations per
      patient). RESULTS: Linear mixed effects models revealed that younger age at
      diagnosis, HR classification, and higher baseline scores were significantly
      associated with poorer outcomes in PS. Patients treated as HR and those with
      higher baseline scores are estimated to have less favorable outcomes in WM and BA
      over time. Parent education and marital status were significantly associated with
      BA and WM baseline scores but not change over time. CONCLUSION: Of the three key
      domains, PS was estimated to have the lowest scores at 5 years after diagnosis.
      Identifying cognitive domains most vulnerable to decline should guide researchers
      who are aiming to develop efficacious cognitive intervention and rehabilitation
      programs, thereby improving the quality of survivorship for the pediatric
      medulloblastoma population.

PMID- 23980080
TI  - Helping survivors of medulloblastoma learn from what we learn.

PMID- 23980082
TI  - David versus Goliath: decision analysis predicts results of a large clinical
      trial in follicular lymphoma.

PMID- 23980081
TI  - German adjuvant intergroup node-positive study: a phase III trial to compare oral
      ibandronate versus observation in patients with high-risk early breast cancer.
AB  - PURPOSE: Bisphosphonates prevent skeletal-related events in patients with
      metastatic breast cancer. Their effect in early breast cancer is controversial.
      Ibandronate is an orally and intravenously available amino-bisphosphonate with a
      favorable toxicity profile. It therefore qualifies as potential agent for
      adjuvant use. PATIENTS AND METHODS: The GAIN (German Adjuvant Intergroup Node
      Positive) study was an open-label, randomized, controlled phase III trial with a
      2 * 2 factorial design. Patients with node-positive early breast cancer were
      randomly assigned 1:1 to two different dose-dense chemotherapy regimens and 2:1
      to ibandronate 50 mg per day orally for 2 years or observation. In all, 2,640
      patients and 728 events were estimated to be required to demonstrate an increase
      in disease-free survival (DFS) by ibandronate from 75% to 79.5% by using a two
      sided alpha = .05 and 1-beta of 80%. We report here the efficacy analysis for
      ibandronate, which was released by the independent data monitoring committee
      because the futility boundary was not crossed after 50% of the required DFS
      events were observed. RESULTS: Between June 2004 and August 2008, 2,015 patients
      were randomly assigned to ibandronate and 1,008 to observation. Patients randomly
      assigned to ibandronate showed no superior DFS or overall survival (OS) compared
      with patients randomly assigned to observation (DFS: hazard ratio, 0.945; 95% CI,
      0.768 to 1.161; P = .589; OS: HR, 1.040; 95% CI, 0.763 to 1.419; P = .803). DFS
      was numerically longer if ibandronate was used in patients younger than 40 years
      or older than 60 years compared with patients age 40 to 59 years (test for
      interaction P = .093). CONCLUSION: Adjuvant treatment with oral ibandronate did
      not improve outcome of patients with high-risk early breast cancer who received
      dose-dense chemotherapy.

PMID- 23980083
TI  - Chemotherapy-induced amenorrhea in patients with breast cancer with a BRCA1 or
      BRCA2 mutation.
AB  - PURPOSE: To determine the likelihood of long-term amenorrhea after treatment with
      chemotherapy in women with breast cancer who carry a BRCA1 or BRCA2 mutation.
      PATIENTS AND METHODS: We conducted a multicenter survey of 1,954 young women with
      a BRCA1 or BRCA2 mutation who were treated for breast cancer. We included
      premenopausal women who were diagnosed with invasive breast cancer between 26 and
      47 years of age. We determined the age of onset of amenorrhea after breast cancer
      for women who were and were not treated with chemotherapy, alone or with
      tamoxifen. We considered chemotherapy-induced amenorrhea to have occurred when
      the patient experienced >= 2 years of amenorrhea, commencing within 2 years of
      initiating chemotherapy, with no resumption of menses. RESULTS: Of the 1,426
      women who received chemotherapy, 35% experienced long-term amenorrhea. Of the 528
      women who did not receive chemotherapy, 5.3% developed long-term amenorrhea. The
      probabilities of chemotherapy-induced amenorrhea were 7.2% for women diagnosed
      before age 30 years, 33% for women age 31 to 44 years, and 79% for women
      diagnosed after age 45 years (P trend < .001). The probability of induced
      amenorrhea was higher for women who received tamoxifen than for those who did not
      (52% v 29%; P < .001). CONCLUSION: Age at treatment and use of tamoxifen are
      important predictors of chemotherapy-induced amenorrhea in women who carry a
      BRCA1 or BRCA2 mutation. The risk of induced long-term amenorrhea does not seem
      to be greater among mutation carriers than among women who do not carry a
      mutation.

PMID- 23980084
TI  - Brivanib versus sorafenib as first-line therapy in patients with unresectable,
      advanced hepatocellular carcinoma: results from the randomized phase III BRISK-FL
      study.
AB  - PURPOSE: Brivanib is a dual inhibitor of vascular-endothelial growth factor and
      fibroblast growth factor receptors that are implicated in the pathogenesis of
      hepatocellular carcinoma (HCC). Our multinational, randomized, double-blind,
      phase III trial compared brivanib with sorafenib as first-line treatment for HCC.
      PATIENTS AND METHODS: Advanced HCC patients who had no prior systemic therapy
      were randomly assigned (ratio, 1:1) to receive sorafenib 400 mg twice daily
      orally (n = 578) or brivanib 800 mg once daily orally (n = 577). Primary end
      point was overall survival (OS). Secondary end points included time to
      progression (TTP), objective response rate (ORR), disease control rate (DCR)
      based on modified Response Evaluation Criteria in Solid Tumors (mRECIST), and
      safety. RESULTS: The primary end point of OS noninferiority for brivanib versus
      sorafenib in the per-protocol population (n = 1,150) was not met (hazard ratio
      [HR], 1.06; 95.8% CI, 0.93 to 1.22), based on the prespecified margin (upper CI
      limit for HR <= 1.08). Median OS was 9.9 months for sorafenib and 9.5 months for
      brivanib. TTP, ORR, and DCR were similar between the study arms. Most frequent
      grade 3/4 adverse events for sorafenib and brivanib were hyponatremia (9% and
      23%, respectively), AST elevation (17% and 14%), fatigue (7% and 15%), hand-foot
      skin reaction (15% and 2%), and hypertension (5% and 13%). Discontinuation as a
      result of adverse events was 33% for sorafenib and 43% for brivanib; rates for
      dose reduction were 50% and 49%, respectively. CONCLUSION: Our study did not meet
      its primary end point of OS noninferiority for brivanib versus sorafenib.
      However, both agents had similar antitumor activity, based on secondary efficacy
      end points. Brivanib had an acceptable safety profile, but was less well
      tolerated than sorafenib.

PMID- 23980085
TI  - Prognostic significance of MTOR pathway component expression in neuroendocrine
      tumors.
AB  - PURPOSE: Clinical studies have implicated the mechanistic target of rapamycin
      (serine/threonine kinase; MTOR) pathway in the regulation of neuroendocrine tumor
      (NET) growth. We explored whether expression of MTOR pathway components has
      prognostic significance in NET patients. PATIENTS AND METHODS: We evaluated
      immunohistochemical expression of MTOR and phospho (p) -MTOR; its downstream
      targets RPS6KB1, RPS6, and EIF4EBP1; and its upstream regulators, in a cohort of
      195 archival neuroendocrine tumors. We correlated expression levels with clinical
      outcomes, after adjusting for other prognostic variables. RESULTS: We observed
      anticipated correlations between expression of upstream components of the MTOR
      pathway and their downstream targets. Expression of PIK3CA, MTOR, or p-EIF4EBP1
      was associated with high MKI67 (Ki-67) labeling index. We failed to identify
      clinical correlations associated with expression of the upstream regulators TSC1,
      TSC2, AKT, p-AKT, PDPK1, PTEN, PIK3R1, or PIK3CA. In contrast, high expression of
      MTOR or its activated downstream targets p-RPS6KB1, p-RPS6, or p-EIF4EBP1 was
      associated with adverse clinical outcomes. CONCLUSION: Our observations suggest
      that expression of MTOR or its downstream targets may be adverse prognostic
      factors in neuroendocrine tumors.

PMID- 23980086
TI  - Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in
      remission: comparison of intravenous busulfan plus cyclophosphamide (Cy) versus
      total-body irradiation plus Cy as conditioning regimen--a report from the acute
      leukemia working party of the European group for blood and marrow
      transplantation.
AB  - PURPOSE: Cyclophosphamide (Cy) combined with total-body irradiation (TBI) or with
      busulfan (Bu) are currently the most common myeloablative regimens used in
      allogeneic stem-cell transplantation (alloSCT) in adults with acute myelogenous
      leukemia (AML). Intravenous (IV) Bu has more predictable bioavailability and a
      safer toxicity profile than the oral formulation. Comparative studies of outcomes
      have been performed between oral Bu/Cy and Cy/TBI, but there have been no
      comparative trials in the era of IV Bu. PATIENTS AND METHODS: We performed a
      retrospective registry-based study comparing outcomes of patients with AML in
      first or second remission after alloSCT from sibling donors who underwent IV
      Bu/Cy (n = 795) or Cy/TBI (n = 864) conditioning. RESULTS: Engraftment rate was
      98% and 99% after IV Bu/Cy and Cy/TBI, respectively. Grade 2 to 4 acute graft
      versus-host disease (GVHD) was significantly lower in the IV Bu/Cy compared with
      Cy/TBI group (P < .001). Similarly, chronic GVHD was significantly lower in the
      IV Bu/Cy compared with Cy/TBI group (P = .003). Cumulative incidence of 2-year
      nonrelapse mortality (NRM; +/- standard deviation [SD]) was 12% +/- 1% in the IV
      Bu/Cy group and 15% +/- 2% in the Cy/TBI group (P = .14), and 2-year relapse
      incidence (RI; +/- SD) was 26% +/- 3% and 21% +/- 1%, respectively (P = .012).
      Leukemia-free survival (LFS) rate (+/- SD) was 61% +/- 2% after IV Bu/Cy and 64%
      +/- 2% after Cy/TBI (P = .27). In multivariable analysis, adjusting for
      differences between both groups, patients who received IV Bu/Cy had lower acute
      and chronic GVHD, higher RI, and a trend toward lower NRM. LFS was not
      statistically different between the two conditioning regimens. CONCLUSION: This
      retrospective study shows that final outcomes after myeloablative conditioning
      using IV Bu/Cy were not statistically different from those after Cy/TBI.

PMID- 23980087
TI  - Quality of life in long-term breast cancer survivors.
AB  - PURPOSE: There is considerable interest in the quality of life (QOL) of long-term
      breast cancer (BC) survivors. We studied changes in QOL from time of BC diagnosis
      to long-term survivorship and compared QOL in long-term survivors to that of age
      matched women with no history of BC. PATIENTS AND METHODS: In all, 535 women with
      localized BC (T1-3N0-1M0) were recruited from 1989 to 1996 and followed
      prospectively, completing QOL questionnaires at diagnosis and 1 year
      postdiagnosis. Between 2005 and 2007, those alive without distant recurrence were
      recontacted to participate in a long-term follow-up (LTFU) study. A control group
      was recruited from women presenting for screening mammograms, and both groups
      completed LTFU QOL questionnaires. Longitudinal change in BC survivors and
      differences between BC survivors and controls were assessed in eight broad
      categories with clinically significant differences set at 5% and 10% of the
      breadth of each QOL scale. RESULTS: A total of 285 patients with BC were included
      in the study, on average 12.5 years postdiagnosis. Longitudinally, clinically
      significant improvements were observed in overall QOL by 1 year postdiagnosis
      with further improvements by LTFU. Some clinically significant improvements over
      time were seen in all categories. A total of 167 controls were recruited.
      Deficits were observed in self-reported cognitive functioning (5.3% difference)
      and financial impact (6.3% difference) in BC survivors at LTFU compared with
      controls. CONCLUSION: Long-term BC survivors show improvement in many domains of
      QOL over time, and they appear to have similar QOL in most respects to age
      matched noncancer controls, although small deficits in cognition and finances
      were identified.

PMID- 23980088
TI  - Brivanib and FOLFOX in hepatocellular carcinoma: finding the common themes among
      negative trials.

PMID- 23980089
TI  - Comparison of outcomes after fluorouracil-based adjuvant therapy for stages II
      and III colon cancer between 1978 to 1995 and 1996 to 2007: evidence of stage
      migration from the ACCENT database.
AB  - PURPOSE: With improved patient care, better diagnosis, and more treatment options
      after tumor recurrence, outcomes after fluorouracil (FU) -based treatment are
      expected to have improved over time in early-stage colon cancer. Data from 18,449
      patients enrolled onto 21 phase III trials conducted from 1978 to 2002 were
      evaluated for potential differences in time to recurrence (TTR), time from
      recurrence to death (TRD), and overall survival (OS) with regard to FU-based
      adjuvant regimens. METHODS: Trials were predefined as old versus newer era using
      initial accrual before or after 1995. Outcomes were compared between patients
      enrolled onto old- or newer-era trials, stratified by stage. RESULTS: Within the
      first 3 years, recurrence rates were lower in newer- versus old-era trials for
      patients with stage II disease, with no differences among those with stage III
      disease. Both TRD and OS were significantly longer in newer-era trials overall
      and within each stage. The lymph node (LN) ratio (ie, number of positive nodes
      divided by total nodes harvested) in those with stage III disease declined over
      time. TTR improved slightly, with larger number of LNs examined in both stages.
      CONCLUSION: Improved TRD in newer trials supports the premise that more
      aggressive intervention (oxaliplatin- and irinotecan-based chemotherapy and/or
      surgery for recurrent disease) improves OS for patients previously treated in the
      adjuvant setting. Lower recurrence rates with identical treatments in those with
      stage II disease enrolled onto newer-era trials reflect stage migration over
      time, calling into question historical data related to the benefit of FU-based
      adjuvant therapy in such patients.

PMID- 23980090
TI  - Brivanib in patients with advanced hepatocellular carcinoma who were intolerant
      to sorafenib or for whom sorafenib failed: results from the randomized phase III
      BRISK-PS study.
AB  - PURPOSE: Brivanib is a selective dual inhibitor of vascular endothelial growth
      factor and fibroblast growth factor receptors implicated in tumorigenesis and
      angiogenesis in hepatocellular carcinoma (HCC). An unmet medical need persists
      for patients with HCC whose tumors do not respond to sorafenib or who cannot
      tolerate it. This multicenter, double-blind, randomized, placebo-controlled trial
      assessed brivanib in patients with HCC who had been treated with sorafenib.
      PATIENTS AND METHODS: In all, 395 patients with advanced HCC who progressed
      on/after or were intolerant to sorafenib were randomly assigned (2:1) to receive
      brivanib 800 mg orally once per day plus best supportive care (BSC) or placebo
      plus BSC. The primary end point was overall survival (OS). Secondary end points
      included time to progression (TTP), objective response rate (ORR), and disease
      control rate based on modified Response Evaluation Criteria in Solid Tumors
      (mRECIST) and safety. RESULTS: Median OS was 9.4 months for brivanib and 8.2
      months for placebo (hazard ratio [HR], 0.89; 95.8% CI, 0.69 to 1.15; P = .3307).
      Adjusting treatment effect for baseline prognostic factors yielded an OS HR of
      0.81 (95% CI, 0.63 to 1.04; P = .1044). Exploratory analyses showed a median time
      to progression of 4.2 months for brivanib and 2.7 months for placebo (HR, 0.56;
      95% CI, 0.42 to 0.76; P < .001), and an mRECIST ORR of 10% for brivanib and 2%
      for placebo (odds ratio, 5.72). Study discontinuation due to treatment-related
      adverse events (AEs) occurred in 61 brivanib patients (23%) and nine placebo
      patients (7%). The most frequent treatment-related grade 3 to 4 AEs for brivanib
      included hypertension (17%), fatigue (13%), hyponatremia (11%), and decreased
      appetite (10%). CONCLUSION: In patients with HCC who had been treated with
      sorafenib, brivanib did not significantly improve OS. The observed benefit in the
      secondary outcomes of TTP and ORR warrants further investigation.

PMID- 23980091
TI  - Gefitinib versus placebo in completely resected non-small-cell lung cancer:
      results of the NCIC CTG BR19 study.
AB  - PURPOSE: Survival of patients with completely resected non-small-cell lung cancer
      (NSCLC) is unsatisfactory, and in 2002, the benefit of adjuvant chemotherapy was
      not established. This phase III study assessed the impact of postoperative
      adjuvant gefitinib on overall survival (OS). PATIENTS AND METHODS: Patients with
      completely resected (stage IB, II, or IIIA) NSCLC stratified by stage, histology,
      sex, postoperative radiotherapy, and chemotherapy were randomly assigned (1:1) to
      receive gefitinib 250 mg per day or placebo for 2 years. Study end points were
      OS, disease-free survival (DFS), and toxicity. RESULTS: As a result of early
      closure, 503 of 1,242 planned patients were randomly assigned (251 to gefitinib
      and 252 to placebo). Baseline factors were balanced between the arms. With a
      median of 4.7 years of follow-up (range, 0.1 to 6.3 years), there was no
      difference in OS (hazard ratio [HR], 1.24; 95% CI, 0.94 to 1.64; P = .14) or DFS
      (HR, 1.22; 95% CI, 0.93 to 1.61; P = .15) between the arms. Exploratory analyses
      demonstrated no DFS (HR, 1.28; 95% CI, 0.92 to 1.76; P = .14) or OS benefit (HR,
      1.24; 95% CI, 0.90 to 1.71; P = .18) from gefitinib for 344 patients with
      epidermal growth factor receptor (EGFR) wild-type tumors. Similarly, there was no
      DFS (HR, 1.84; 95% CI, 0.44 to 7.73; P = .395) or OS benefit (HR, 3.16; 95% CI,
      0.61 to 16.45; P = .15) from gefitinib for the 15 patients with EGFR mutation
      positive tumors. Adverse events were those expected with an EGFR inhibitor.
      Serious adverse events occurred in <= 5% of patients, except infection, fatigue,
      and pain. One patient in each arm had fatal pneumonitis. CONCLUSION: Although the
      trial closed prematurely and definitive statements regarding the efficacy of
      adjuvant gefitinib cannot be made, these results indicate that it is unlikely to
      be of benefit.

PMID- 23980092
TI  - Stomach cancer risk after treatment for hodgkin lymphoma.
AB  - PURPOSE: Treatment-related stomach cancer is an important cause of morbidity and
      mortality among the growing number of Hodgkin lymphoma (HL) survivors, but risks
      associated with specific HL treatments are unclear. PATIENTS AND METHODS: We
      conducted an international case-control study of stomach cancer nested in a
      cohort of 19,882 HL survivors diagnosed from 1953 to 2003, including 89 cases and
      190 matched controls. For each patient, we quantified cumulative doses of
      specific alkylating agents (AAs) and reconstructed radiation dose to the stomach
      tumor location. RESULTS: Stomach cancer risk increased with increasing radiation
      dose to the stomach (Ptrend < .001) and with increasing number of AA-containing
      chemotherapy cycles (Ptrend = .02). Patients who received both radiation to the
      stomach >= 25 Gy and high-dose procarbazine (>= 5,600 mg/m(2)) had strikingly
      elevated stomach cancer risk (25 cases, two controls; odds ratio [OR], 77.5; 95%
      CI, 14.7 to 1452) compared with those who received radiation < 25 Gy and
      procarbazine < 5,600 mg/m(2) (Pinteraction < .001). Risk was also elevated (OR,
      2.8; 95% CI, 1.3 to 6.4) among patients who received radiation to the stomach >=
      25 Gy but procarbazine < 5,600 mg/m(2); however, no procarbazine-related risk was
      evident with radiation < 25 Gy. Treatment with dacarbazine also increased stomach
      cancer risk (12 cases, nine controls; OR, 8.8; 95% CI, 2.1 to 46.6), after
      adjustment for radiation and procarbazine doses. CONCLUSION: Patients with HL who
      received subdiaphragmatic radiotherapy had dose-dependent increased risk of
      stomach cancer, with marked risks for patients who also received chemotherapy
      containing high-dose procarbazine. For current patients, risks and benefits of
      exposure to both procarbazine and subdiaphragmatic radiotherapy should be weighed
      carefully. For patients treated previously, GI symptoms should be evaluated
      promptly.

PMID- 23980093
TI  - Integrative radiogenomic profiling of squamous cell lung cancer.
AB  - Radiotherapy is one of the mainstays of anticancer treatment, but the
      relationship between the radiosensitivity of cancer cells and their genomic
      characteristics is still not well defined. Here, we report the development of a
      high-throughput platform for measuring radiation survival in vitro and its
      validation in comparison with conventional clonogenic radiation survival
      analysis. We combined results from this high-throughput assay with genomic
      parameters in cell lines from squamous cell lung carcinoma, which is standardly
      treated by radiotherapy, to identify parameters that predict radiation
      sensitivity. We showed that activation of NFE2L2, a frequent event in lung
      squamous cancers, confers radiation resistance. An expression-based, in silico
      screen nominated inhibitors of phosphoinositide 3-kinase (PI3K) as NFE2L2
      antagonists. We showed that the selective PI3K inhibitor, NVP-BKM120, both
      decreased NRF2 protein levels and sensitized NFE2L2 or KEAP1-mutant cells to
      radiation. We then combined results from this high-throughput assay with single
      sample gene set enrichment analysis of gene expression data. The resulting
      analysis identified pathways implicated in cell survival, genotoxic stress,
      detoxification, and innate and adaptive immunity as key correlates of radiation
      sensitivity. The integrative and high-throughput methods shown here for large
      scale profiling of radiation survival and genomic features of solid-tumor-derived
      cell lines should facilitate tumor radiogenomics and the discovery of genotype
      selective radiation sensitizers and protective agents.

PMID- 23980094
TI  - A comparative genomic approach for identifying synthetic lethal interactions in
      human cancer.
AB  - Synthetic lethal interactions enable a novel approach for discovering specific
      genetic vulnerabilities in cancer cells that can be exploited for the development
      of therapeutics. Despite successes in model organisms such as yeast, discovering
      synthetic lethal interactions on a large scale in human cells remains a
      significant challenge. We describe a comparative genomic strategy for identifying
      cancer-relevant synthetic lethal interactions whereby candidate interactions are
      prioritized on the basis of genetic interaction data available in yeast, followed
      by targeted testing of candidate interactions in human cell lines. As a proof of
      principle, we describe two novel synthetic lethal interactions in human cells
      discovered by this approach, one between the tumor suppressor gene SMARCB1 and
      PSMA4, and another between alveolar soft-part sarcoma-associated ASPSCR1 and
      PSMC2. These results suggest therapeutic targets for cancers harboring mutations
      in SMARCB1 or ASPSCR1 and highlight the potential of a targeted, cross-species
      strategy for identifying synthetic lethal interactions relevant to human cancer.

PMID- 23980095
TI  - NSD2 is recruited through its PHD domain to oncogenic gene loci to drive multiple
      myeloma.
AB  - Histone lysine methyltransferase NSD2 (WHSC1/MMSET) is overexpressed frequently
      in multiple myeloma due to the t(4;14) translocation associated with 15% to 20%
      of cases of this disease. NSD2 has been found to be involved in myelomagenesis,
      suggesting it may offer a novel therapeutic target. Here we show that NSD2
      methyltransferase activity is crucial for clonogenicity, adherence, and
      proliferation of multiple myeloma cells on bone marrow stroma in vitro and that
      NSD2 is required for tumorigenesis of t(4;14)+ but not t(4;14)- multiple myeloma
      cells in vivo. The PHD domains in NSD2 were important for its cellular activity
      and biological function through recruiting NSD2 to its oncogenic target genes and
      driving their transcriptional activation. By strengthening its disease linkage
      and deepening insights into its mechanism of action, this study provides a
      strategy to therapeutically target NSD2 in multiple myeloma patients with a
      t(4;14) translocation.

PMID- 23980096
TI  - Strawberry notch homologue 2 regulates osteoclast fusion by enhancing the
      expression of DC-STAMP.
AB  - Osteoclasts are multinucleated cells formed by fusion of mononuclear precursors
      in response to receptor activator of nuclear factor kappaB (NF-kappaB) ligand
      (RANKL). We found that RANKL induced expression of the DExD/H helicase family
      corepressor strawberry notch homologue 2 (Sbno2). Previous in vitro studies
      showed that Sbno2 is induced by IL-10 and is involved in NF-kappaB repression.
      However, the role of Sbno2 in vivo and its pleiotropic functions are unknown.
      Sbno2 gene targeting resulted in normal NF-kappaB activation by TLR ligands.
      However, Sbno2-deficient mice exhibited increased bone mass due to impaired
      osteoclast fusion. Expression of dendritic cell-specific transmembrane protein
      (DC-STAMP), a critical player in osteoclast fusion, was significantly attenuated,
      and cell fusion of Sbno2-deficient osteoclasts was rescued by DC-STAMP. Sbno2
      directly bound to T cell acute lymphocytic leukemia 1 (Tal1) and attenuated its
      inhibition of DC-STAMP expression, leading to activation of the DC-STAMP promoter
      by microphthalmia-associated transcription factor (MITF). Thus, Sbno2 plays a
      pivotal role in bone homeostasis in vivo by fine-tuning osteoclast fusion. 

PMID- 23980097
TI  - The Nlrp3 inflammasome regulates acute graft-versus-host disease.
AB  - The success of allogeneic hematopoietic cell transplantation is limited by acute
      graft-versus-host disease (GvHD), a severe complication accompanied by high
      mortality rates. Yet, the molecular mechanisms initiating this disease remain
      poorly defined. In this study, we show that, after conditioning therapy,
      intestinal commensal bacteria and the damage-associated molecular pattern uric
      acid contribute to Nlrp3 inflammasome-mediated IL-1beta production and that
      gastrointestinal decontamination and uric acid depletion reduced GvHD severity.
      Early blockade of IL-1beta or genetic deficiency of the IL-1 receptor in
      dendritic cells (DCs) and T cells improved survival. The Nlrp3 inflammasome
      components Nlrp3 and Asc, which are required for pro-IL-1beta cleavage, were
      critical for the full manifestation of GvHD. In transplanted mice, IL-1beta
      originated from multiple intestinal cell compartments and exerted its effects on
      DCs and T cells, the latter being preferentially skewed toward Th17. Compatible
      with these mouse data, increased levels of active caspase-1 and IL-1beta were
      found in circulating leukocytes and intestinal GvHD lesions of patients. Thus,
      the identification of a crucial role for the Nlrp3 inflammasome sheds new light
      on the pathogenesis of GvHD and opens a potential new avenue for the targeted
      therapy of this severe complication. 

PMID- 23980098
TI  - CD4+ T cells are trigger and target of the glucocorticoid response that prevents
      lethal immunopathology in toxoplasma infection.
AB  - Synthetic glucocorticoids (GCs) are commonly used in the treatment of
      inflammatory diseases, but the role of endogenous GCs in the regulation of host
      protective immune responses is poorly understood. Here we show that GCs are
      induced during acute Toxoplasma gondii infection and directly control the T cell
      response to the parasite. When infected with toxoplasma, mice that selectively
      lack GC receptor (GR) expression in T cells (GR(lck-Cre)) rapidly succumb to
      infection despite displaying parasite burdens indistinguishable from control
      animals and unaltered levels of the innate cytokines IL-12 and IL-27. Mortality
      in the GR(lck-Cre) mice was associated with immunopathology and hyperactive Th1
      cell function as revealed by enhanced IFN-gamma and TNF production in vivo.
      Unexpectedly, these CD4(+) T lymphocytes also overexpressed IL-10. Importantly,
      CD4(+) T cell depletion in wild-type or GR(lck-Cre) mice led to ablation of the
      GC response to infection. Moreover, in toxoplasma-infected RAG(-/-) animals,
      adoptive transfer of CD4(+) T lymphocytes was required for GC induction. These
      findings establish a novel IL-10-independent immunomodulatory circuit in which
      CD4(+) T cells trigger a GC response that in turn dampens their own effector
      function. In the case of T. gondii infection, this self-regulatory pathway is
      critical for preventing collateral tissue damage and promoting host survival. 

PMID- 23980099
TI  - Negative selection, not receptor editing, is a physiological response of
      autoreactive thymocytes.
AB  - Antigen receptor editing-a process of secondary rearrangements of antigen
      receptor genes in autoreactive lymphocytes-is a well-established tolerance
      mechanism in B cells, whereas its role in T cells remains controversial. Here, we
      investigated this issue using a novel Tcra knock-in locus, which ensured
      appropriate timing of TCRalpha expression and allowed secondary rearrangements.
      Under these conditions the only response to self-antigen that could be
      unambiguously identified was negative selection of CD4/CD8 double positive
      thymocytes. No evidence could be obtained for antigen-induced TCR editing,
      whereas replacement of the transgenic TCRalpha chain by ongoing gene
      rearrangement occurred in some cells irrespective of the presence or absence of
      self-antigen. 

PMID- 23980104
TI  - Transcriptional profiling of Neisseria meningitidis interacting with human
      epithelial cells in a long-term in vitro colonization model.
AB  - Neisseria meningitidis is a commensal of humans that can colonize the
      nasopharyngeal epithelium for weeks to months and occasionally invades to cause
      life-threatening septicemia and meningitis. Comparatively little is known about
      meningococcal gene expression during colonization beyond those first few hours.
      In this study, the transcriptome of adherent serogroup B N. meningitidis strain
      MC58 was determined at intervals during prolonged cocultivation with confluent
      monolayers of the human respiratory epithelial cell line 16HBE14. At different
      time points up to 21 days, 7 to 14% of the meningococcal genome was found to be
      differentially regulated. The transcriptome of adherent meningococci obtained
      after 4 h of coculture was markedly different from that obtained after prolonged
      cocultivation (24 h, 96 h, and 21 days). Genes persistently upregulated during
      prolonged cocultivation included three genes (hfq, misR/phoP, and lrp) encoding
      global regulatory proteins. Many genes encoding known adhesins involved in
      epithelial adherence were upregulated, including those of a novel locus (spanning
      NMB0342 to NMB0348 [NMB0342-NMB0348]) encoding epithelial cell-adhesive function.
      Sixteen genes (including porA, porB, rmpM, and fbpA) encoding proteins previously
      identified by their immunoreactivity to sera from individuals colonized long term
      with serogroup B meningococci were also upregulated during prolonged
      cocultivation, indicating that our system models growth conditions in vivo during
      the commensal state. Surface-expressed proteins downregulated in the nasopharynx
      (and thus less subject to selection pressure) but upregulated in the bloodstream
      (and thus vulnerable to antibody-mediated bactericidal activity) should be
      interesting candidate vaccine antigens, and in this study, three new proteins
      fulfilling these criteria have been identified: NMB0497, NMB0866, and NMB1882. 

PMID- 23980105
TI  - CD38 controls the innate immune response against Listeria monocytogenes.
AB  - CD38, adenosine-5'-diphosphate-ribosyl cyclase 1, is a multifunctional enzyme,
      expressed on a wide variety of cell types. CD38 has been assigned diverse
      functions, including generation of calcium-mobilizing metabolites, cell
      activation, and chemotaxis. Using a murine Listeria monocytogenes infection
      model, we found that CD38 knockout (KO) mice were highly susceptible to
      infection. Enhanced susceptibility was already evident within 3 days of
      infection, suggesting a function of CD38 in the innate immune response. CD38 was
      expressed on neutrophils and inflammatory monocytes, and especially inflammatory
      monocytes further upregulated CD38 during infection. Absence of CD38 caused
      alterations of the migration pattern of both cell types to sites of infection. We
      observed impaired accumulation of cells in the spleen but surprisingly similar or
      even higher accumulation of cells in the liver. CD38 KO and wild-type mice showed
      similar changes in the composition of neutrophils and inflammatory monocytes in
      blood and bone marrow, indicating that mobilization of these cells from the bone
      marrow was CD38 independent. In vitro, macrophages of CD38 KO mice were less
      efficient in uptake of listeria but still able to kill the bacteria. Dendritic
      cells also displayed enhanced CD38 expression following infection. However,
      absence of CD38 did not impair the capacity of mice to prime CD8(+) T cells
      against L. monocytogenes, and CD38 KO mice could efficiently control secondary
      listeria infection. In conclusion, our results demonstrate an essential role for
      CD38 in the innate immune response against L. monocytogenes. 

PMID- 23980106
TI  - Relative contributions of lipooligosaccharide inner and outer core modifications
      to nontypeable Haemophilus influenzae pathogenesis.
AB  - Nontypeable Haemophilus influenzae (NTHi) is a frequent commensal of the human
      nasopharynx that causes opportunistic infection in immunocompromised individuals.
      Existing evidence associates lipooligosaccharide (LOS) with disease, but the
      specific and relative contributions of NTHi LOS modifications to virulence
      properties of the bacterium have not been comprehensively addressed. Using NTHi
      strain 375, an isolate for which the detailed LOS structure has been determined,
      we compared systematically a set of isogenic mutant strains expressing
      sequentially truncated LOS. The relative contributions of 2-keto-3
      deoxyoctulosonic acid, the triheptose inner core, oligosaccharide extensions on
      heptoses I and III, phosphorylcholine, digalactose, and sialic acid to NTHi
      resistance to antimicrobial peptides (AMP), self-aggregation, biofilm formation,
      cultured human respiratory epithelial infection, and murine pulmonary infection
      were assessed. We show that opsX, lgtF, lpsA, lic1, and lic2A contribute to
      bacterial resistance to AMP; lic1 is related to NTHi self-aggregation; lgtF,
      lic1, and siaB are involved in biofilm growth; opsX and lgtF participate in
      epithelial infection; and opsX, lgtF, and lpsA contribute to lung infection.
      Depending on the phenotype, the involvement of these LOS modifications occurs at
      different extents, independently or having an additive effect in combination. We
      discuss the relative contribution of LOS epitopes to NTHi virulence and frame a
      range of pathogenic traits in the context of infection. 

PMID- 23980107
TI  - The Haemophilus ducreyi Fis protein is involved in controlling expression of the
      lspB-lspA2 operon and other virulence factors.
AB  - Expression of the lspB-lspA2 operon encoding a virulence-related two-partner
      secretion system in Haemophilus ducreyi 35000HP is directly regulated by the
      CpxRA regulatory system (M. Labandeira-Rey, J. R. Mock, and E. J. Hansen, Infect.
      Immun. 77:3402-3411, 2009). In the present study, we show that this secretion
      system is also regulated by the small nucleoid-associated protein Fis.
      Inactivation of the H. ducreyi fis gene resulted in a reduction in expression of
      both the H. ducreyi LspB and LspA2 proteins. DNA microarray experiments showed
      that a H. ducreyi fis deletion mutant exhibited altered expression levels of
      genes encoding other important H. ducreyi virulence factors, including DsrA and
      Flp1, suggesting a possible global role for Fis in the control of virulence in
      this obligate human pathogen. While the H. ducreyi Fis protein has a high degree
      of sequence and structural similarity to the Fis proteins of other bacteria, its
      temporal pattern of expression was very different from that of enterobacterial
      Fis proteins. The use of a lacZ-based transcriptional reporter provided evidence
      which indicated that the H. ducreyi Fis homolog is a positive regulator of gyrB,
      a gene that is negatively regulated by Fis in enteric bacteria. Taken together,
      the Fis protein expression data and the observed regulatory effects of Fis in H.
      ducreyi suggest that this small DNA binding protein has a regulatory role in H.
      ducreyi which may differ in substantial ways from that of other Fis proteins. 

PMID- 23980108
TI  - MrkD1P from Klebsiella pneumoniae strain IA565 allows for coexistence with
      Pseudomonas aeruginosa and protection from protease-mediated biofilm detachment.
AB  - Biofilm formation and persistence are essential components for the continued
      survival of pathogens inside the host and constitute a major contributor to the
      development of chronic wounds with resistance to antimicrobial compounds.
      Understanding these processes is crucial for control of biofilm-mediated disease.
      Though chronic wound infections are often polymicrobial in nature, much of the
      research on chronic wound-related microbes has focused on single-species models.
      Klebsiella pneumoniae and Pseudomonas aeruginosa are microbes that are often
      found together in wound isolates and are able to form stable in vitro biofilms,
      despite the antagonistic nature of P. aeruginosa with other organisms. Mutants of
      the K. pneumoniae strain IA565 lacking the plasmid-borne mrkD1P gene were less
      competitive than the wild type in an in vitro dual-species biofilm model with P.
      aeruginosa (PAO1). PAO1 spent medium inhibited the formation of biofilm of mrkD1P
      deficient mutants and disrupted preestablished biofilms, with no effect on IA565
      and no effect on the growth of the wild type or mutants. A screen using a two
      allele PAO1 transposon library identified the LasB elastase as the secreted
      effector involved in biofilm disruption, and a purified version of the protein
      produced results similar to those with PAO1 spent medium. Various other proteases
      had a similar effect, suggesting that the disruption of the mrkD1P gene causes
      sensitivity to general proteolytic effects and indicating a role for MrkD1P in
      protection against host antibiofilm effectors. Our results suggest that MrkD1P
      allows for competition of K. pneumoniae with P. aeruginosa in a mixed-species
      biofilm and provides defense against microbial and host-derived proteases. 

PMID- 23980109
TI  - Natural variation in the promoter of the gene encoding the Mga regulator alters
      host-pathogen interactions in group a Streptococcus carrier strains.
AB  - Humans commonly carry pathogenic bacteria asymptomatically, but the molecular
      factors underlying microbial asymptomatic carriage are poorly understood. We
      previously reported that two epidemiologically unassociated serotype M3 group A
      Streptococcus (GAS) carrier strains had an identical 12-bp deletion in the
      promoter of the gene encoding Mga, a global positive gene regulator. Herein, we
      report on studies designed to test the hypothesis that the identified 12-bp
      deletion in the mga promoter alters GAS virulence, thereby potentially
      contributing to the asymptomatic carrier phenotype. Using allelic exchange, we
      introduced the variant promoter into a serotype M3 invasive strain and the wild
      type promoter into an asymptomatic carrier strain. Compared to strains with the
      wild-type mga promoter, we discovered that strains containing the promoter with
      the 12-bp deletion produced significantly fewer mga and Mga-regulated gene
      transcripts. Consistent with decreased mga transcripts, strains containing the
      variant mga promoter were also significantly less virulent in in vivo and ex vivo
      models of GAS disease. Further, we provide evidence that the pleiotropic
      regulator protein CodY binds to the mga promoter and that the 12-bp deletion in
      the mga promoter reduces CodY-mediated mga transcription. We conclude that the
      naturally occurring 12-bp deletion in the mga promoter significantly alters the
      pathogen-host interaction of these asymptomatic carrier strains. Our findings
      provide new insight into the molecular basis of the carrier state of an important
      human pathogen. 

PMID- 23980110
TI  - Cellular response to Trypanosoma cruzi infection induces secretion of defensin
      alpha-1, which damages the flagellum, neutralizes trypanosome motility, and
      inhibits infection.
AB  - Human defensins play a fundamental role in the initiation of innate immune
      responses to some microbial pathogens. Here we show that colonic epithelial model
      HCT116 cells respond to Trypanosoma cruzi infection by secreting defensin alpha
      1, which reduces infection. We also report the early effects of defensin alpha-1
      on invasive trypomastigotes that involve damage of the flagellar structure to
      inhibit parasite motility and reduce cellular infection. Short exposure of
      defensin alpha-1 to trypomastigotes shows that defensin alpha-1 binds to the
      flagellum, resulting in flagellar membrane and axoneme alterations, followed by
      breaking of the flagellar membrane connected to the trypanosome body, leading to
      detachment and release of the parasite flagellum. In addition, defensin alpha-1
      induces a significant reduction in parasite motility in a peptide concentration
      dependent manner, which is abrogated by anti-defensin alpha-1 IgG. Preincubation
      of trypomastigotes with a concentration of defensin alpha-1 that inhibits 50%
      trypanosome motility significantly reduced cellular infection by 80%. Thus, human
      defensin alpha-1 is an innate immune molecule that is secreted by HCT116 cells in
      response to T. cruzi infection, inhibits T. cruzi motility, and plays an
      important role in reducing cellular infection. This is the first report showing a
      novel cellular innate immune response to a human parasite by secretion of
      defensin alpha-1, which neutralizes the motility of a human parasite to reduce
      cellular infection. The mode of activity of human defensin alpha-1 against T.
      cruzi and its function may provide insights for the development of new
      antiparasitic strategies. 

PMID- 23980111
TI  - Characterization of sil in invasive group A and G streptococci: antibodies
      against bacterial pheromone peptide SilCR result in severe infection.
AB  - Group G beta-hemolytic streptococcus (GGS) strains cause severe invasive
      infections, mostly in patients with comorbidities. GGS is known to possess
      virulence factors similar to those of its more virulent counterpart group A
      streptococcus (GAS). A streptococcal invasion locus, sil, was identified in GAS.
      sil encodes a competence-stimulating peptide named SilCR that activates bacterial
      quorum sensing and has the ability to attenuate virulence in GAS infections. We
      found that sil is present in most GGS strains (82%) but in only 25% of GAS
      strains, with a similar gene arrangement. GGS strains that contained sil
      expressed the SilCR peptide and secreted it into the growth medium. In a modified
      murine model of GGS soft tissue infection, GGS grown in the presence of SilCR
      caused a milder disease than GGS grown in the absence of SilCR. To further study
      the role of the peptide in bacterial virulence attenuation, we vaccinated mice
      with SilCR to produce specific anti-SilCR antibodies. Vaccinated mice developed a
      significantly more severe illness than nonvaccinated mice. Our results indicate
      that the sil locus is much more prevalent among the less virulent GGS strains
      than among GAS strains. GGS strains express and secrete SilCR, which has a role
      in attenuation of virulence in a murine model. We show that the SilCR peptide can
      protect mice from infection caused by GGS. Furthermore, vaccinated mice that
      produce specific anti-SilCR antibodies develop a significantly more severe
      infection. To our knowledge, this is a novel report demonstrating that specific
      antibodies against a bacterial component cause more severe infection by those
      bacteria. 

PMID- 23980112
TI  - The RNA chaperone Hfq is required for virulence of Bordetella pertussis.
AB  - Bordetella pertussis is a Gram-negative pathogen causing the human respiratory
      disease called pertussis or whooping cough. Here we examined the role of the RNA
      chaperone Hfq in B. pertussis virulence. Hfq mediates interactions between small
      regulatory RNAs and their mRNA targets and thus plays an important role in
      posttranscriptional regulation of many cellular processes in bacteria, including
      production of virulence factors. We characterized an hfq deletion mutant
      (Deltahfq) of B. pertussis 18323 and show that the Deltahfq strain produces
      decreased amounts of the adenylate cyclase toxin that plays a central role in B.
      pertussis virulence. Production of pertussis toxin and filamentous hemagglutinin
      was affected to a lesser extent. In vitro, the ability of the Deltahfq strain to
      survive within macrophages was significantly reduced compared to that of the wild
      type (wt) strain. The virulence of the Deltahfq strain in the mouse respiratory
      model of infection was attenuated, with its capacity to colonize mouse lungs
      being strongly reduced and its 50% lethal dose value being increased by one order
      of magnitude over that of the wt strain. In mixed-infection experiments, the
      Deltahfq strain was then clearly outcompeted by the wt strain. This requirement
      for Hfq suggests involvement of small noncoding RNA regulation in B. pertussis
      virulence. 

PMID- 23980113
TI  - Short-lived effector CD8 T cells induced by genetically attenuated malaria
      parasite vaccination express CD11c.
AB  - Vaccination with a single dose of genetically attenuated malaria parasites can
      induce sterile protection against sporozoite challenge in the rodent Plasmodium
      yoelii model. Protection is dependent on CD8(+) T cells, involves perforin and
      gamma interferon (IFN-gamma), and is correlated with the expansion of effector
      memory CD8(+) T cells in the liver. Here, we have further characterized vaccine
      induced changes in the CD8(+) T cell phenotype and demonstrated significant
      upregulation of CD11c on CD3(+) CD8b(+) T cells in the liver, spleen, and
      peripheral blood. CD11c(+) CD8(+) T cells are predominantly CD11a(hi) CD44(hi)
      CD62L(-), indicative of antigen-experienced effector cells. Following in vitro
      restimulation with malaria-infected hepatocytes, CD11c(+) CD8(+) T cells
      expressed inflammatory cytokines and cytotoxicity markers, including IFN-gamma,
      tumor necrosis factor alpha (TNF-alpha), interleukin-2 (IL-2), perforin, and
      CD107a. CD11c(-) CD8(+) T cells, on the other hand, expressed negligible amounts
      of all inflammatory cytokines and cytotoxicity markers tested, indicating that
      CD11c marks multifunctional effector CD8(+) T cells. Coculture of CD11c(+), but
      not CD11c(-), CD8(+) T cells with sporozoite-infected primary hepatocytes
      significantly inhibited liver-stage parasite development. Tetramer staining for
      the immunodominant circumsporozoite protein (CSP)-specific CD8(+) T cell epitope
      demonstrated that approximately two-thirds of CSP-specific cells expressed CD11c
      at the peak of the CD11c(+) CD8(+) T cell response, but CD11c expression was lost
      as the CD8(+) T cells entered the memory phase. Further analyses showed that
      CD11c(+) CD8(+) T cells are primarily KLRG1(+) CD127(-) terminal effectors,
      whereas all KLRG1(-) CD127(+) memory precursor effector cells are CD11c(-) CD8(+)
      T cells. Together, these results suggest that CD11c marks a subset of highly
      inflammatory, short-lived, antigen-specific effector cells, which may play an
      important role in eliminating infected hepatocytes. 

PMID- 23980114
TI  - Secreted pyomelanin of Legionella pneumophila promotes bacterial iron uptake and
      growth under iron-limiting conditions.
AB  - Iron acquisition is critical to the growth and virulence of Legionella
      pneumophila. Previously, we found that L. pneumophila uses both a
      ferrisiderophore pathway and ferrous iron transport to obtain iron. We now report
      that two molecules secreted by L. pneumophila, homogentisic acid (HGA) and its
      polymerized variant (HGA-melanin, a pyomelanin), are able to directly mediate the
      reduction of various ferric iron salts. Furthermore, HGA, synthetic HGA-melanin,
      and HGA-melanin derived from bacterial supernatants enhanced the ability of L.
      pneumophila and other species of Legionella to take up radiolabeled iron.
      Enhanced iron uptake was not observed with a ferrous iron transport mutant. Thus,
      HGA and HGA-melanin mediate ferric iron reduction, with the resulting ferrous
      iron being available to the bacterium for uptake. Upon further testing of L.
      pneumophila culture supernatants, we found that significant amounts of ferric and
      ferrous iron were associated with secreted HGA-melanin. Importantly, a pyomelanin
      containing fraction obtained from a wild-type culture supernatant was able to
      stimulate the growth of iron-starved legionellae. That the corresponding
      supernatant fraction obtained from a nonpigmented mutant culture did not
      stimulate growth demonstrated that HGA-melanin is able to both promote iron
      uptake and enhance growth under iron-limiting conditions. Indicative of a
      complementary role in iron acquisition, HGA-melanin levels were inversely related
      to the levels of siderophore activity. Compatible with a role in the ecology and
      pathogenesis of L. pneumophila, HGA and HGA-melanin were effective at reducing
      and releasing iron from both insoluble ferric hydroxide and the mammalian iron
      chelates ferritin and transferrin. 

PMID- 23980116
TI  - Oxidant-induced corticosteroid unresponsiveness in human bronchial epithelial
      cells.
AB  - BACKGROUND: We hypothesised that increased oxidative stress, as present in the
      airways of asthma and chronic obstructive pulmonary disease (COPD) patients,
      induces epithelial damage and reduces epithelial responsiveness to suppressive
      effects of corticosteroids on proinflammatory cytokine production and barrier
      function. METHODS: We induced oxidative stress by H2O2 and/or cigarette smoke
      extract (CSE) in human bronchial epithelial 16HBE cells and primary bronchial
      epithelial cells (PBEC) derived by brushings from asthma patients, COPD patients,
      and smoking and non-smoking control individuals. We investigated effects of
      budesonide on barrier function (electrical resistance) and TNF-alpha-induced
      proinflammatory cytokine production (IL-8/CXCL8, granulocyte macrophage-colony
      stimulating factor (GM-CSF)). RESULTS: We observed that H2O2 and CSE reduce
      epithelial resistance. Budesonide significantly counteracted this effect, likely
      by protection against epidermal growth factor receptor-dependent cell-cell
      contact disruption. Furthermore, budesonide suppressed proinflammatory cytokine
      production. H2O2 pretreatment reduced this effect of budesonide on cytokine
      production in both 16HBE cells and PBECs. Importantly, PBECs from asthma and COPD
      patients were less sensitive to budesonide with respect to cytokine production
      and barrier function than PBECs from control subjects. CONCLUSIONS: Together, our
      data indicate that budesonide suppresses epithelial proinflammatory responses and
      barrier dysfunction and that oxidative stress reduces these effects in airway
      epithelium from asthma and COPD patients. Therefore, restoration of
      corticosteroid responsiveness in asthma and COPD may act to improve the airway
      epithelial barrier.

PMID- 23980115
TI  - The acyl-homoserine lactone synthase YenI from Yersinia enterocolitica modulates
      virulence gene expression in enterohemorrhagic Escherichia coli O157:H7.
AB  - The human pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7 colonizes
      the rectoanal junction (RAJ) in cattle, its natural reservoir. Colonization at
      the RAJ poses a serious risk for fecal shedding and contamination of the
      environment. We previously demonstrated that EHEC senses acyl-homoserine lactones
      (AHLs) produced by the microbiota in the rumen to activate the gad acid
      resistance genes necessary for survival through the acidic stomachs in cattle and
      to repress the locus of enterocyte effacement (LEE) genes important for
      colonization of the RAJ, but unnecessary in the rumen. Devoid of AHLs, the RAJ is
      the prominent site of colonization of EHEC in cattle. To determine if the
      presence of AHLs in the RAJ could repress colonization at this site, we
      engineered EHEC to express the Yersinia enterocolitica AHL synthase gene yenI,
      which constitutively produces AHLs, to mimic a constant exposure of AHLs in the
      environment. The yenI(+) EHEC produces oxo-C6-homoserine lactone (oxo-C6-HSL) and
      had a significant reduction in LEE expression, effector protein secretion, and
      attaching and effacing (A/E) lesion formation in vitro compared to the wild type
      (WT). The yenI(+) EHEC also activated expression of the gad genes. To assess
      whether AHL production, which decreases LEE expression, would decrease RAJ
      colonization by EHEC, cattle were challenged at the RAJ with WT or yenI(+) EHEC.
      Although the yenI(+) EHEC colonized the RAJ with efficiency equal to that of the
      WT, there was a trend for the cattle to shed the WT strain longer than the
      yenI(+) EHEC. 

PMID- 23980117
TI  - Asthma admissions, smoking bans and administrative databases.

PMID- 23980118
TI  - Signs of adaptation to local pH conditions across an environmental mosaic in the
      California Current Ecosystem.
AB  - Little is known about the potential for rapid evolution in natural populations in
      response to the high rate of contemporary climatic change. Organisms that have
      evolved in environments that experience high variability across space and time
      are of particular interest as they may harbor genetic variation that can
      facilitate evolutionary response to changing conditions. Here we review what is
      known about genetic capacity for adaptation in the purple sea urchin,
      Strongylocentrotus purpuratus, a species that has evolved in the upwelling
      ecosystem of the Northeast Pacific Ocean. We also present new results testing for
      adaptation to local pH conditions in six populations from Oregon to southern
      California. We integrate data on 19,493 genetic polymorphisms with data on local
      pH conditions. We find correlations between allele frequency and rank average
      time spent at pH <7.8 in 318 single-nucleotide polymorphisms in 275 genes. Two of
      the genes most correlated with local pH are a protein associated with the
      cytoskeleton and a proton pump, with functional roles in maintenance of cell
      volume and with internal regulation of pH, respectively. Across all loci tested,
      high correlations with local pH were concentrated in genes related to transport
      of ions, biomineralization, lipid metabolism, and cell-cell adhesion, functional
      pathways important for maintaining homeostasis at low pH. We identify a set of
      seven genes as top candidates for rapid evolutionary response to acidification of
      the ocean. In these genes, the putative low-pH-adapted allele, based on allele
      frequencies in natural populations, rapidly increases in frequency in purple sea
      urchin larvae raised at low pH. We also found that populations from localities
      with high pH show a greater change in allele frequency toward putative low-pH
      adapted alleles under experimental acidification, compared with low-pH
      populations, suggesting that both natural and artificial selection favor the same
      alleles for response to low pH. These results illustrate that purple sea urchins
      may be adapted to local pH and suggest that this species may possess the genetic
      capacity for rapid evolution in response to acidification. This adaptive capacity
      likely comes from standing genetic variation maintained in nature by balancing
      selection across the spatial and temporal environmental mosaic that characterizes
      the California Current Ecosystem. 

PMID- 23980120
TI  - Validation of blood and liver oxymorphone analysis using LC-MS-MS: concentrations
      in 30 fatal overdoses.
AB  - A sensitive liquid chromatography-tandem mass spectrometry method was developed
      and validated for the quantitation of oxymorphone (OM) in human whole blood and
      liver. Sample preparation was done by solid-phase extraction, using deuterated OM
      as the internal standard. Separation was achieved using a Waters Aquity UPLC HSS
      T3 column. Analysis utilized positive electrospray ionization and multiple
      reaction monitoring. As part of the validation, studies were conducted to
      determine potential interference, selectivity, ion suppression/enhancement and
      carryover. Calibration model, limit of detection (LOD), lower limit of
      quantitation (LLOQ), precision and accuracy were also established. The linear
      range of the method was 2-500 ng/mL in blood and 5-500 ng/g in the liver. The LOD
      and LLOQ were 2 ng/mL for blood and 5 ng/g for the liver. Blood and/or liver
      specimens from 30 cases were analyzed. OM concentrations ranged from 23 to 554
      ng/mL ( , n = 26) in blood and 48 to 1740 ng/g ( , n = 30) in the liver. 

PMID- 23980119
TI  - Do older patients and their family caregivers agree about the quality of chronic
      illness care?
AB  - OBJECTIVE: Family caregivers often accompany patients to medical visits; however,
      it is unclear whether caregivers rate the quality of patients' care similarly to
      patients. This study aimed to (1) quantify the level of agreement between
      patients' and caregivers' reports on the quality of patients' care and (2)
      determine how the level of agreement varies by caregiver and patient
      characteristics. DESIGN: Cross-sectional analysis. PARTICIPANTS: Multimorbid
      older (aged 65 and above) adults and their family caregivers (n = 247). METHODS:
      Quality of care was rated separately by patients and their caregivers using the
      Patient Assessment of Chronic Illness Care (PACIC) instrument. The level of
      agreement was examined using a weighted kappa statistic (Kw). RESULTS: Agreement
      of caregivers' and patients' PACIC scores was low (Kw = 0.15). Patients taking
      ten or more medications per day showed less agreement with their caregivers about
      the quality of care than patients taking five or fewer medications (Kw = 0.03 and
      0.34, respectively, P < 0.05). Caregivers who reported greater difficulty
      assisting patients with health care tasks had less agreement with patients about
      the quality of care being provided when compared with caregivers who reported no
      difficulty (Kw = -0.05 and 0.31, respectively, P < .05). Patient-caregiver dyads
      had greater agreement on objective questions than on subjective questions (Kw =
      0.25 and 0.15, respectively, P > 0.05). CONCLUSION: Patient-caregiver dyads
      following a more complex treatment plan (i.e. taking many medications) or having
      more difficulty following a treatment plan (i.e. having difficulty with health
      care tasks) had less agreement. Future qualitative research is needed to
      elucidate the underlying reasons patients and caregivers rate the quality of care
      differently.

PMID- 23980121
TI  - Aftermath of a clinical trial: evaluating the sustainability of a medical device
      intervention in Ghana.
AB  - A randomized controlled trial recently demonstrated that continuous positive
      airway pressure (CPAP) effectively decreases respiratory rate in children
      presenting to Ghanaian district hospitals with respiratory distress. A follow-up
      study 16 months later evaluated the extent to which the skills and equipment
      necessary for CPAP use have been maintained. Seven of eight CPAP machines were
      functional, but five of eight oxygen concentrators and three of four electric
      generators were non-functional. Nurses trained by US study personnel (first
      generation) and nurses trained by Ghanaian nurses after the study (second
      generation) were evaluated on CPAP knowledge and skills. Twenty-eight nurses
      participated in the study, 9 first-generation and 19 second-generation. First
      generation trainees scored significantly higher than second-generation trainees
      on both skills and knowledge assessments (p = 0.003). Appropriate technical
      support and training must be ensured to address equipment maintenance.
      Protocolization of the training program, in conjunction with skills and knowledge
      assessment, may improve acquisition and retention among second- and future
      generation trainees. 

PMID- 23980122
TI  - Fcgamma receptors enable anticancer action of proapoptotic and immune-modulatory
      antibodies.
AB  - Antibodies have important roles in controlling cellular immunity through
      interaction with activating or inhibitory Fcgamma receptors (FcgammaRs). FcgammaR
      engagement can facilitate receptor cross-linking on target cells, or induce
      retrograde FcgammaR signals to stimulate or suppress antibody-dependent, cell
      mediated depletion of antigen-bearing target cells. Recent studies uncover
      unexpectedly important roles for FcgammaRs in the anticancer action of antibodies
      designed to trigger tumor cell apoptosis or enhance antitumor immunity. Here, we
      outline a conceptual framework for understanding these findings and discuss their
      mechanistic and translational implications. 

PMID- 23980123
TI  - Subverting sterols: rerouting an oxysterol-signaling pathway to promote tumor
      growth.
AB  - Oxysterols are oxidized derivatives of cholesterol that are generated
      enzymatically or through autoxidation. Initially identified as important lipid
      signaling molecules in the context of atherosclerosis and inflammation,
      accumulated evidence indicates that these lipid-signaling molecules can have
      pleiotropic effects on the fate and function of the immune system. These effects
      range from the regulation of immune cell survival and proliferation to chemotaxis
      and antiviral immunity. New studies now indicate that tumor-derived oxysterols
      can serve to subvert the immune system by recruiting protumorigenic neutrophils
      into the tumor microenvironment. The consequence of this recruitment is the
      generation of proangiogenic factors and matrix metalloproteinase proteins that
      provide a tumor a significant growth and survival advantage. In combination with
      other recent studies, these data highlight the ongoing cross talk between sterol
      metabolism and the immune system, and they raise the intriguing possibility that
      targeting oxysterol pathways could serve as a novel therapeutic approach in the
      war on cancer. 

PMID- 23980124
TI  - Advice.

PMID- 23980125
TI  - Simplifying nerve monitoring.

PMID- 23980126
TI  - Response to "simplifying nerve monitoring".

PMID- 23980128
TI  - Co-morbid infections in Hansen's disease patients in the United States:
      considerations for treatment.
AB  - 120 patients attending a Hansen's disease public health satellite clinic were
      evaluated for selected latent co-morbidities, consisting of strongyloidiasis,
      Chagas disease, hepatitis B, HIV, and tuberculosis, and potential exacerbation by
      immunosuppressive therapy. Implications for treatment of Hansen's disease are
      discussed.

PMID- 23980129
TI  - Identification of concurrent bacterial infection in adult patients with dengue.
AB  - We aim to construct a diagnostic model for bacterial coinfection in dengue
      patients (Dengue Dual Infection Score [DDIS]); 2,065 adult dengue patients (mean
      age = 41.9 +/- 17.2 years, 58.4% male, 83 patients with bacterial coinfection)
      seen at a university hospital from January of 2005 to February of 2010 were
      studied. The DDIS was created by assigning one point to each of five risk factors
      for bacterial coinfection: pulse rate >= 90 beats/minute, total white cell count
      >= 6 * 10(9)/L, hematocrit < 40%, serum sodium < 135 mmol/L, and serum urea >= 5
      mmol/L. The DDIS identified bacterial coinfection (derivation set area under the
      curve = 0.793, 95% confidence interval = 0.732-0.854; validation set area under
      the curve = 0.761, 95% confidence interval = 0.637-0.886). A DDIS of >= 4 had a
      specificity of 94.4%, whereas a DDIS of >= 1 had a sensitivity of 94.4% for
      bacterial coinfection. The DDIS can help to select dengue patients for early
      bacterial cultures and empirical antibiotics.

PMID- 23980130
TI  - In vitro susceptibility of Leishmania donovani to miltefosine in Indian visceral
      leishmaniasis.
AB  - Promastigote miltefosine (MIL) susceptibility was performed on Leishmania
      donovani isolates from Indian patients with visceral leishmaniasis treated with
      MIL. Isolates that were obtained before the onset of MIL treatment, after
      completion of treatment (29th day), or at the time of treatment failure, were
      screened using in vitro promastigote assay. The MIL susceptibility of the pre
      treatment isolates (N = 24, mean IC50 +/- SEM = 3.74 +/- 0.38 MUM) was
      significantly higher than that of the post-treatment group (N = 26, mean IC50 +/-
      SEM = 6.15 +/- 0.52 MUM; P = 0.0006) but was similar in the cured patients (N =
      22, mean IC50 +/- SEM = 5.58 +/- 0.56 MUM) and those who failed treatment (N =
      28, mean IC50 +/- SEM = 4.53 +/- 0.47 MUM). The pre/post-treatment results thus
      showed a 2-fold difference, whereas isolated from cured versus failed patients
      showed a similar susceptibility, suggesting that this higher tolerance is not
      responsible for MIL-treatment failure. Our work highlights the need for careful
      monitoring of MIL susceptibility for implementation in national VL elimination
      programs.

PMID- 23980131
TI  - Cost-effectiveness analysis of introducing RDTs for malaria diagnosis as compared
      to microscopy and presumptive diagnosis in central and peripheral public health
      facilities in Ghana.
AB  - Cost-effectiveness information on where malaria rapid diagnostic tests (RDTs)
      should be introduced is limited. We developed incremental cost-effectiveness
      analyses with data from rural health facilities in Ghana with and without
      microscopy. In the latter, where diagnosis had been presumptive, the introduction
      of RDTs increased the proportion of patients who were correctly treated in
      relation to treatment with antimalarials, from 42% to 65% at an incremental
      societal cost of Ghana cedis (GHS)12.2 (US$8.3) per additional correctly treated
      patients. In the "microscopy setting" there was no advantage to replacing
      microscopy by RDT as the cost and proportion of correctly treated patients were
      similar. Results were sensitive to a decrease in the cost of RDTs, which cost
      GHS1.72 (US$1.17) per test at the time of the study and to improvements in
      adherence to negative tests that was just above 50% for both RDTs and microscopy.

PMID- 23980132
TI  - A modified semi-nested multiplex malaria PCR (SnM-PCR) for the identification of
      the five human Plasmodium species occurring in Southeast Asia.
AB  - We have modified an existing semi-nested multiplex polymerase chain reaction
      (PCR) by adding one Plasmodium knowlesi-specific nested PCR, and validated the
      latter against laboratory and clinical samples. This new method has the advantage
      of being relatively affordable in low resource settings while identifying the
      five human Plasmodium species with a three-step PCR.

PMID- 23980133
TI  - Enteral arginine partially ameliorates parenteral nutrition-induced small
      intestinal atrophy and stimulates hepatic protein synthesis in neonatal piglets.
AB  - BACKGROUND: Arginine is an indispensable amino acid in neonates; de novo
      synthesis of arginine occurs in the small intestine (SI) but is reduced during
      parenteral nutrition (PN), limiting the arginine available to the mucosa. We
      assessed the effects of route of intake and dietary concentration of arginine on
      protein synthesis, superior mesenteric artery (SMA) blood flow, and SI
      morphology. METHODS: Piglets (n = 18, 14-17 days old) were given complete PN for
      3 days to induce SI atrophy, then switched to 1 of 3 treatments: arginine-free PN
      plus an intragastric (IG) infusion of high arginine (1.6 g . kg(-1). d(-1), IG-H
      Arg) or low arginine (0.6 g . kg(-1). d(-1), IG-L Arg) or complete high-arginine
      PN (1.6 g . kg(-1). d(-1), IV-H Arg). RESULTS: Enteral arginine, irrespective of
      amount provided, stimulated hepatic protein synthesis compared with intravenous
      delivery of arginine (P = .01). SMA blood flow declined for all groups following
      the initiation of PN. After 48 hours on the test diets, all groups reached low
      constant levels, but the IV-H group was significantly higher than both IG groups
      (P < .05). Despite greater blood flow, the SI morphological characteristics in IV
      H Arg pigs were not significantly improved over the other groups. IV-H Arg pigs
      had higher plasma concentrations of indispensable amino acids (tyrosine,
      isoleucine, and valine) compared with IG-H Arg, despite identical amino acid
      intakes. CONCLUSIONS: Intravenous delivery of arginine sustained the best SMA
      blood flow, whereas even a moderate amount of enteral arginine stimulated liver
      protein synthesis and maintained SI growth, independent of blood flow.

PMID- 23980134
TI  - Bedside ultrasound is a practical and reliable measurement tool for assessing
      quadriceps muscle layer thickness.
AB  - BACKGROUND: Critically ill patients commonly experience skeletal muscle wasting
      that may predict clinical outcome. Ultrasound is a noninvasive method that can
      measure muscle quadriceps muscle layer thickness (QMLT) and subsequently lean
      body mass (LBM) at the bedside. However, currently the reliability of these
      measurements are unknown. The objectives of this study were to evaluate the intra
      and interreliability of measuring QMLT using bedside ultrasound. METHODS:
      Ultrasound measurements of QMLT were conducted at 7 centers on healthy
      volunteers. Trainers were instructed to perform measurements twice on each
      patient, and then a second trainee repeated the measurement. Intrarater
      reliability measured how consistently the same person measured the subject
      according to intraclass correlation (ICC). Interrater reliability measured how
      consistently trainer and trainee agreed when measuring the same subject according
      to the ICC. RESULTS: We collected 42 pairs of within operator measurements with
      an ICC of .98 and 78 pairs of trainer-to-trainee measurements with an ICC of .95.
      There were no statistically significant differences between the trainer and
      trainee results (trainer and trainee mean = -0.028 cm, 95% CI = -0.067 to -0.011,
      P = .1607). CONCLUSIONS: Excellent intra- and interrater reliability for
      ultrasound measurements of QMLT in healthy volunteers was observed when performed
      by a range of providers with no prior ultrasound experience, including
      dietitians, nurses, physicians, and research assistants. This technique shows
      promise as a method to evaluate LBM status in ICU or hospital settings and as a
      method to assess the effects of nutrition and exercise-based interventions on
      muscle wasting.

PMID- 23980135
TI  - The prevalence of sarcopenia in patients with respiratory failure classified as
      normally nourished using computed tomography and subjective global assessment.
AB  - BACKGROUND: Declines in nutrition status and adverse body composition changes
      frequently occur in the critically ill. The objective of this cross-sectional
      study was to examine the prevalence of sarcopenia and its occurrence in patients
      classified as normal nourished using subjective global assessment (SGA). METHODS:
      Exploiting diagnostic CT images, skeletal muscle mass at the L3 region was
      quantified and used to determine sarcopenia and its association with normal
      nutrition status in 56 patients with respiratory failure. Sarcopenia was defined
      as an L3 skeletal muscle index of <=38.5 cm(2)/m(2) for women and <=52.4
      cm(2)/m(2) for men. CT imaging and SGA classifications completed within 14, 10
      and 7 days of each other were analyzed to assess sarcopenia and the influence of
      time between scans on misclassification (ie, normal nourished and sarcopenic).
      Descriptive statistics were conducted. RESULTS: The average patient was 59.2 (+/-
      15.6) years old, admitted with sepsis/infection, an APACHE II score of 26 (+/-
      8.0), and BMI of 28.3 (+/- 5.8). Sarcopenia and sarcopenic obesity were prevalent
      in a minimum of 56% and 24% of patients, respectively, depending on the number of
      days between CT imaging and SGA assessment. Misclassified individuals were
      predominantly male, minority and overweight or obese. Controlling for age, no
      significant differences were noted for patients classified as normal nourished vs
      malnourished by SGA for lumbar muscle cross-sectional, whole-body lean mass, or
      skeletal muscle index. CONCLUSIONS: Sarcopenia is highly prevalent among patients
      with respiratory failure requiring mechanical ventilation (MV) and not readily
      detected in patients classified as normal nourished using SGA.

PMID- 23980136
TI  - Contribution of solar radiation to decadal temperature variability over land.
AB  - Global air temperature has become the primary metric for judging global climate
      change. The variability of global temperature on a decadal timescale is still
      poorly understood. This paper examines further one suggested hypothesis, that
      variations in solar radiation reaching the surface (Rs) have caused much of the
      observed decadal temperature variability. Because Rs only heats air during the
      day, its variability is plausibly related to the variability of diurnal
      temperature range (daily maximum temperature minus its minimum). We show that the
      variability of diurnal temperature range is consistent with the variability of Rs
      at timescales from monthly to decadal. This paper uses long comprehensive
      datasets for diurnal temperature range to establish what has been the
      contribution of Rs to decadal temperature variability. It shows that Rs over land
      globally peaked in the 1930s, substantially decreased from the 1940s to the
      1970s, and changed little after that. Reduction of Rs caused a reduction of more
      than 0.2  degrees C in mean temperature during May to October from the 1940s
      through the 1970s, and a reduction of nearly 0.2  degrees C in mean air
      temperature during November to April from the 1960s through the 1970s. This
      cooling accounts in part for the near-constant temperature from the 1930s into
      the 1970s. Since then, neither the rapid increase in temperature from the 1970s
      through the 1990s nor the slowdown of warming in the early twenty-first century
      appear to be significantly related to changes of Rs. 

PMID- 23980137
TI  - Mouse model implicates GNB3 duplication in a childhood obesity syndrome.
AB  - Obesity is a highly heritable condition and a risk factor for other diseases,
      including type 2 diabetes, cardiovascular disease, hypertension, and cancer.
      Recently, genomic copy number variation (CNV) has been implicated in cases of
      early onset obesity that may be comorbid with intellectual disability. Here, we
      describe a recurrent CNV that causes a syndrome associated with intellectual
      disability, seizures, macrocephaly, and obesity. This unbalanced chromosome
      translocation leads to duplication of over 100 genes on chromosome 12, including
      the obesity candidate gene G protein beta3 (GNB3). We generated a transgenic
      mouse model that carries an extra copy of GNB3, weighs significantly more than
      its wild-type littermates, and has excess intraabdominal fat accumulation. GNB3
      is highly expressed in the brain, consistent with G-protein signaling involved in
      satiety and/or metabolism. These functional data connect GNB3 duplication and
      overexpression to elevated body mass index and provide evidence for a genetic
      syndrome caused by a recurrent CNV. 

PMID- 23980138
TI  - Anion translocation through an Slc26 transporter mediates lumen expansion during
      tubulogenesis.
AB  - Lumen formation is a critical event in biological tube formation, yet its
      molecular mechanisms remain poorly understood. Specifically, how lumen expansion
      is coordinated with other processes of tubulogenesis is not well known, and the
      role of membrane transporters in tubulogenesis during development has not been
      adequately addressed. Here we identify a solute carrier 26 (Slc26) family protein
      as an essential regulator of tubulogenesis using the notochord of the
      invertebrate chordate Ciona intestinalis as a model. Ci-Slc26aalpha is
      indispensable for lumen formation and expansion, but not for apical/luminal
      membrane formation and lumen connection. Ci-Slc26aalpha acts as an anion
      transporter, mediating the electrogenic exchange of sulfate or oxalate for
      chloride or bicarbonate and electroneutral chloride:bicarbonate exchange. Mutant
      rescue assays show that this transport activity is essential for Ci-Slc26aalpha's
      in vivo function. Our work reveals the consequences and relationships of several
      key processes in lumen formation, and establishes an in vivo assay for studying
      the molecular basis of the transport properties of SLC26 family transporters and
      their related diseases. 

PMID- 23980139
TI  - Money and trust among strangers.
AB  - What makes money essential for the functioning of modern society? Through an
      experiment, we present evidence for the existence of a relevant behavioral
      dimension in addition to the standard theoretical arguments. Subjects faced
      repeated opportunities to help an anonymous counterpart who changed over time.
      Cooperation required trusting that help given to a stranger today would be
      returned by a stranger in the future. Cooperation levels declined when going from
      small to large groups of strangers, even if monitoring and payoffs from
      cooperation were invariant to group size. We then introduced intrinsically
      worthless tokens. Tokens endogenously became money: subjects took to reward help
      with a token and to demand a token in exchange for help. Subjects trusted that
      strangers would return help for a token. Cooperation levels remained stable as
      the groups grew larger. In all conditions, full cooperation was possible through
      a social norm of decentralized enforcement, without using tokens. This turned out
      to be especially demanding in large groups. Lack of trust among strangers thus
      made money behaviorally essential. To explain these results, we developed an
      evolutionary model. When behavior in society is heterogeneous, cooperation
      collapses without tokens. In contrast, the use of tokens makes cooperation
      evolutionarily stable. 

PMID- 23980140
TI  - Integration of responses within and across Arabidopsis natural accessions
      uncovers loci controlling root systems architecture.
AB  - Phenotypic plasticity is presumed to be involved in adaptive change toward
      species diversification. We thus examined how candidate genes underlying natural
      variation across populations might also mediate plasticity within an individual.
      Our implementation of an integrative "plasticity space" approach revealed that
      the root plasticity of a single Arabidopsis accession exposed to distinct
      environments broadly recapitulates the natural variation "space." Genome-wide
      association mapping identified the known gene PHOSPHATE 1 (PHO1) and other genes
      such as Root System Architecture 1 (RSA1) associated with differences in root
      allometry, a highly plastic trait capturing the distribution of lateral roots
      along the primary axis. The response of mutants in the Columbia-0 background
      suggests their involvement in signaling key modulators of root development
      including auxin, abscisic acid, and nitrate. Moreover, genotype-by-environment
      interactions for the PHO1 and RSA1 genes in Columbia-0 phenocopy the root
      allometry of other natural variants. This finding supports a role for plasticity
      responses in phenotypic evolution in natural environments. 

PMID- 23980141
TI  - Expanding the primate body schema in sensorimotor cortex by virtual touches of an
      avatar.
AB  - The brain representation of the body, called the body schema, is susceptible to
      plasticity. For instance, subjects experiencing a rubber hand illusion develop a
      sense of ownership of a mannequin hand when they view it being touched while
      tactile stimuli are simultaneously applied to their own hand. Here, the cortical
      basis of such an embodiment was investigated through concurrent recordings from
      primary somatosensory (i.e., S1) and motor (i.e., M1) cortical neuronal ensembles
      while two monkeys observed an avatar arm being touched by a virtual ball.
      Following a period when virtual touches occurred synchronously with physical
      brushes of the monkeys' arms, neurons in S1 and M1 started to respond to virtual
      touches applied alone. Responses to virtual touch occurred 50 to 70 ms later than
      to physical touch, consistent with the involvement of polysynaptic pathways
      linking the visual cortex to S1 and M1. We propose that S1 and M1 contribute to
      the rubber hand illusion and that, by taking advantage of plasticity in these
      areas, patients may assimilate neuroprosthetic limbs as parts of their body
      schema. 

PMID- 23980142
TI  - Cognitive emotion regulation fails the stress test.
AB  - Cognitive emotion regulation has been widely shown in the laboratory to be an
      effective way to alter the nature of emotional responses. Despite its success in
      experimental contexts, however, we often fail to use these strategies in everyday
      life where stress is pervasive. The successful execution of cognitive regulation
      relies on intact executive functioning and engagement of the prefrontal cortex,
      both of which are rapidly impaired by the deleterious effects of stress. Because
      it is specifically under stressful conditions that we may benefit most from such
      deliberate forms of emotion regulation, we tested the efficacy of cognitive
      regulation after stress exposure. Participants first underwent fear-conditioning,
      where they learned that one stimulus (CS+) predicted an aversive outcome but
      another predicted a neutral outcome (CS-). Cognitive regulation training directly
      followed where participants were taught to regulate fear responses to the
      aversive stimulus. The next day, participants underwent an acute stress induction
      or a control task before repeating the fear-conditioning task using these newly
      acquired regulation skills. Skin conductance served as an index of fear arousal,
      and salivary alpha-amylase and cortisol concentrations were assayed as
      neuroendocrine markers of stress response. Although groups showed no differences
      in fear arousal during initial fear learning, nonstressed participants
      demonstrated robust fear reduction following regulation training, whereas
      stressed participants showed no such reduction. Our results suggest that stress
      markedly impairs the cognitive regulation of emotion and highlights critical
      limitations of this technique to control affective responses under stress. 

PMID- 23980143
TI  - Magnetotactic bacteria form magnetite from a phosphate-rich ferric hydroxide via
      nanometric ferric (oxyhydr)oxide intermediates.
AB  - The iron oxide mineral magnetite (Fe3O4) is produced by various organisms to
      exploit magnetic and mechanical properties. Magnetotactic bacteria have become
      one of the best model organisms for studying magnetite biomineralization, as
      their genomes are sequenced and tools are available for their genetic
      manipulation. However, the chemical route by which magnetite is formed
      intracellularly within the so-called magnetosomes has remained a matter of
      debate. Here we used X-ray absorption spectroscopy at cryogenic temperatures and
      transmission electron microscopic imaging techniques to chemically characterize
      and spatially resolve the mechanism of biomineralization in those microorganisms.
      We show that magnetite forms through phase transformation from a highly
      disordered phosphate-rich ferric hydroxide phase, consistent with prokaryotic
      ferritins, via transient nanometric ferric (oxyhydr)oxide intermediates within
      the magnetosome organelle. This pathway remarkably resembles recent results on
      synthetic magnetite formation and bears a high similarity to suggested
      mineralization mechanisms in higher organisms. 

PMID- 23980144
TI  - Ether lipid generating enzyme AGPS alters the balance of structural and signaling
      lipids to fuel cancer pathogenicity.
AB  - Aberrant lipid metabolism is an established hallmark of cancer cells. In
      particular, ether lipid levels have been shown to be elevated in tumors, but
      their specific function in cancer remains elusive. We show here that the
      metabolic enzyme alkylglyceronephosphate synthase (AGPS), a critical step in the
      synthesis of ether lipids, is up-regulated across multiple types of aggressive
      human cancer cells and primary tumors. We demonstrate that ablation of AGPS in
      cancer cells results in reduced cell survival, cancer aggressiveness, and tumor
      growth through altering the balance of ether lipid, fatty acid, eicosanoid, and
      fatty acid-derived glycerophospholipid metabolism, resulting in an overall
      reduction in the levels of several oncogenic signaling lipids. Taken together,
      our results reveal that AGPS, in addition to maintaining ether lipids, also
      controls cellular utilization of fatty acids, favoring the generation of
      signaling lipids necessary for promoting the aggressive features of cancer. 

PMID- 23980145
TI  - Tuning the redox activity of encapsulated metal clusters via the metallic and
      semiconducting character of carbon nanotubes.
AB  - We demonstrate that reactions confined within single-walled carbon nanotube
      (SWCNT) channels are modulated by the metallic and semiconducting character of
      the hosts. In situ Raman and X-ray absorption near-edge structure spectroscopies
      provide complementary information about the electronic state of carbon nanotubes
      and the encapsulated rhenium species, which reveal electronic interactions
      between encapsulated species and nanotubes. More electrons are transferred from
      metallic tubes (m-SWCNTs) to oxidic rhenium clusters, leading to a lower valence
      state rhenium oxide than that in semiconducting tubes (s-SWCNTs). Reduction in
      3.5% (vol/vol) H2/Ar leads to weakened host-guest electronic interaction. The
      high valence state Re within s-SWCNTs is more readily reduced when raising the
      temperature, whereas only a sluggish change is observed for Re within m-SWCNTs.
      Only at 400  degrees C does Re reach a similar electronic state (mixture of Re(0)
      and Re(4+)) in both types of tubes. Subsequent oxidation in 1% O2/Ar does not
      show changes for Re in s-SWCNTs up to 200  degrees C. In comparison, m-SWCNTs
      facilitate the oxidation of reduced rhenium (160  degrees C). This can be
      exploited for rational design of active catalysts with stable species as a
      desired valence state can be obtained by selecting specific-type SWCNTs and a
      controlled thermal treatment. These results also provide a chemical approach to
      modulate reversibly the electronic structure of SWCNTs without damaging the
      sidewalls of SWCNTs. 

PMID- 23980146
TI  - Superpriming of synaptic vesicles after their recruitment to the readily
      releasable pool.
AB  - Recruitment of release-competent vesicles during sustained synaptic activity is
      one of the major factors governing short-term plasticity. During bursts of
      synaptic activity, vesicles are recruited to a fast-releasing pool from a
      reluctant vesicle pool through an actin-dependent mechanism. We now show that
      newly recruited vesicles in the fast-releasing pool do not respond at full speed
      to a strong Ca(2+) stimulus, but require approximately 4 s to mature to a
      "superprimed" state. Superpriming was found to be altered by agents that modulate
      the function of unc13 homolog proteins (Munc13s), but not by calmodulin
      inhibitors or actin-disrupting agents. These findings indicate that recruitment
      and superpriming of vesicles are regulated by separate mechanisms, which require
      integrity of the cytoskeleton and activation of Munc13s, respectively. We propose
      that refilling of the fast-releasing vesicle pool proceeds in two steps, rapid
      actin-dependent "positional priming," which brings vesicles closer to Ca(2+)
      sources, followed by slower superpriming, which enhances the Ca(2+) sensitivity
      of primed vesicles. 

PMID- 23980147
TI  - Cellular capsules as a tool for multicellular spheroid production and for
      investigating the mechanics of tumor progression in vitro.
AB  - Deciphering the multifactorial determinants of tumor progression requires
      standardized high-throughput preparation of 3D in vitro cellular assays. We
      present a simple microfluidic method based on the encapsulation and growth of
      cells inside permeable, elastic, hollow microspheres. We show that this approach
      enables mass production of size-controlled multicellular spheroids. Due to their
      geometry and elasticity, these microcapsules can uniquely serve as quantitative
      mechanical sensors to measure the pressure exerted by the expanding spheroid. By
      monitoring the growth of individual encapsulated spheroids after confluence, we
      dissect the dynamics of pressure buildup toward a steady-state value, consistent
      with the concept of homeostatic pressure. In turn, these confining conditions are
      observed to increase the cellular density and affect the cellular organization of
      the spheroid. Postconfluent spheroids exhibit a necrotic core cemented by a blend
      of extracellular material and surrounded by a rim of proliferating hypermotile
      cells. By performing invasion assays in a collagen matrix, we report that
      peripheral cells readily escape preconfined spheroids and cell-cell cohesivity is
      maintained for freely growing spheroids, suggesting that mechanical cues from the
      surrounding microenvironment may trigger cell invasion from a growing tumor.
      Overall, our technology offers a unique avenue to produce in vitro cell-based
      assays useful for developing new anticancer therapies and to investigate the
      interplay between mechanics and growth in tumor evolution. 

PMID- 23980148
TI  - Learning-induced neural plasticity of speech processing before birth.
AB  - Learning, the foundation of adaptive and intelligent behavior, is based on
      plastic changes in neural assemblies, reflected by the modulation of electric
      brain responses. In infancy, auditory learning implicates the formation and
      strengthening of neural long-term memory traces, improving discrimination skills,
      in particular those forming the prerequisites for speech perception and
      understanding. Although previous behavioral observations show that newborns react
      differentially to unfamiliar sounds vs. familiar sound material that they were
      exposed to as fetuses, the neural basis of fetal learning has not thus far been
      investigated. Here we demonstrate direct neural correlates of human fetal
      learning of speech-like auditory stimuli. We presented variants of words to
      fetuses; unlike infants with no exposure to these stimuli, the exposed fetuses
      showed enhanced brain activity (mismatch responses) in response to pitch changes
      for the trained variants after birth. Furthermore, a significant correlation
      existed between the amount of prenatal exposure and brain activity, with greater
      activity being associated with a higher amount of prenatal speech exposure.
      Moreover, the learning effect was generalized to other types of similar speech
      sounds not included in the training material. Consequently, our results indicate
      neural commitment specifically tuned to the speech features heard before birth
      and their memory representations. 

PMID- 23980149
TI  - GABA(B) autoreceptor-mediated cell type-specific reduction of inhibition in
      epileptic mice.
AB  - GABA(B) receptors (GABA(B)Rs) mediate slow inhibitory effects on neuronal
      excitability and synaptic transmission in the brain. However, the GABA(B)R
      agonist baclofen can also promote excitability and seizure generation in human
      patients and animals models. Here we show that baclofen has concentration
      dependent effects on the hippocampal network in a mouse model of mesial temporal
      lobe epilepsy. Application of baclofen at a high dose (10 mg/kg i.p.) reduced the
      power of gamma oscillations and the frequency of pathological discharges in the
      Cornu Ammonis area 3 (CA3) area of freely moving epileptic mice. Unexpectedly, at
      a lower dose (1 mg/kg), baclofen markedly increased gamma activity accompanied by
      a higher incidence of pathological discharges. Intracellular recordings from CA3
      pyramidal cells in vitro further revealed that, although at a high concentration
      (10 uM), baclofen invariably resulted in hyperpolarization, at low concentrations
      (0.5 uM), the drug had divergent effects, producing depolarization and an
      increase in firing frequency in epileptic but not control mice. These excitatory
      effects were mediated by the selective muting of inhibitory cholecystokinin
      positive basket cells (CCK(+) BCs), through enhanced inhibition of GABA release
      via presynaptic GABA(B)Rs. We conclude that cell type-specific up-regulation of
      GABA(B)R-mediated autoinhibition in CCK(+) BCs promotes aberrant high frequency
      oscillations and hyperexcitability in hippocampal networks of chronic epileptic
      mice.

PMID- 23980150
TI  - Insulin growth factor signaling is regulated by microRNA-486, an underexpressed
      microRNA in lung cancer.
AB  - MicroRNAs (miRNAs) are small 19- to 24-nt noncoding RNAs that have the capacity
      to regulate fundamental biological processes essential for cancer initiation and
      progression. In cancer, miRNAs may function as oncogenes or tumor suppressors.
      Here, we conducted global profiling for miRNAs in a cohort of stage 1 nonsmall
      cell lung cancers (n = 81) and determined that miR-486 was the most down
      regulated miRNA in tumors compared with adjacent uninvolved lung tissues,
      suggesting that miR-486 loss may be important in lung cancer development. We
      report that miR-486 directly targets components of insulin growth factor (IGF)
      signaling including insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R),
      and phosphoinositide-3-kinase, regulatory subunit 1 (alpha) (PIK3R1, or p85a) and
      functions as a potent tumor suppressor of lung cancer both in vitro and in vivo.
      Our findings support the role for miR-486 loss in lung cancer and suggest a
      potential biological link to p53. 

PMID- 23980151
TI  - Dissection of the BCR-ABL signaling network using highly specific monobody
      inhibitors to the SHP2 SH2 domains.
AB  - The dysregulated tyrosine kinase BCR-ABL causes chronic myelogenous leukemia in
      humans and forms a large multiprotein complex that includes the Src-homology 2
      (SH2) domain-containing phosphatase 2 (SHP2). The expression of SHP2 is necessary
      for BCR-ABL-dependent oncogenic transformation, but the precise signaling
      mechanisms of SHP2 are not well understood. We have developed binding proteins,
      termed monobodies, for the N- and C-terminal SH2 domains of SHP2. Intracellular
      expression followed by interactome analysis showed that the monobodies are
      essentially monospecific to SHP2. Two crystal structures revealed that the
      monobodies occupy the phosphopeptide-binding sites of the SH2 domains and thus
      can serve as competitors of SH2-phosphotyrosine interactions. Surprisingly, the
      segments of both monobodies that bind to the peptide-binding grooves run in the
      opposite direction to that of canonical phosphotyrosine peptides, which may
      contribute to their exquisite specificity. When expressed in cells, monobodies
      targeting the N-SH2 domain disrupted the interaction of SHP2 with its upstream
      activator, the Grb2-associated binder 2 adaptor protein, suggesting decoupling of
      SHP2 from the BCR-ABL protein complex. Inhibition of either N-SH2 or C-SH2 was
      sufficient to inhibit two tyrosine phosphorylation events that are critical for
      SHP2 catalytic activity and to block ERK activation. In contrast, targeting the N
      SH2 or C-SH2 revealed distinct roles of the two SH2 domains in downstream
      signaling, such as the phosphorylation of paxillin and signal transducer and
      activator of transcription 5. Our results delineate a hierarchy of function for
      the SH2 domains of SHP2 and validate monobodies as potent and specific
      antagonists of protein-protein interactions in cancer cells. 

PMID- 23980153
TI  - Tapping unsustainable groundwater stores for agricultural production in the High
      Plains Aquifer of Kansas, projections to 2110.
AB  - Groundwater provides a reliable tap to sustain agricultural production, yet
      persistent aquifer depletion threatens future sustainability. The High Plains
      Aquifer supplies 30% of the nation's irrigated groundwater, and the Kansas
      portion supports the congressional district with the highest market value for
      agriculture in the nation. We project groundwater declines to assess when the
      study area might run out of water, and comprehensively forecast the impacts of
      reduced pumping on corn and cattle production. So far, 30% of the groundwater has
      been pumped and another 39% will be depleted over the next 50 y given existing
      trends. Recharge supplies 15% of current pumping and would take an average of 500
      1,300 y to completely refill a depleted aquifer. Significant declines in the
      region's pumping rates will occur over the next 15-20 y given current trends, yet
      irrigated agricultural production might increase through 2040 because of
      projected increases in water use efficiencies in corn production. Water use
      reductions of 20% today would cut agricultural production to the levels of 15-20
      y ago, the time of peak agricultural production would extend to the 2070s, and
      production beyond 2070 would significantly exceed that projected without reduced
      pumping. Scenarios evaluate incremental reductions of current pumping by 20-80%,
      the latter rate approaching natural recharge. Findings substantiate that saving
      more water today would result in increased net production due to projected future
      increases in crop water use efficiencies. Society has an opportunity now to make
      changes with tremendous implications for future sustainability and livability. 

PMID- 23980154
TI  - Converting stem cells to dendritic cells by agonist antibodies from unbiased
      morphogenic selections.
AB  - When combinatorial antibody libraries are rendered infectious for eukaryotic
      cells, the integrated antibody genotype and cellular phenotype become permanently
      linked and each cell becomes a selection system unto itself. These systems should
      be ideal for the identification of proteins and pathways that regulate
      differentiation so long as selection systems can be devised. Here we use a
      selection system based on the ability of secreted antibodies to alter the
      morphology of colonies expressing them when grown in soft agar. Importantly, this
      approach is different from all previous studies in that it used a pure discovery
      format where unbiased libraries that were not preselected against any known
      protein were used as probes. As such, the strategy is analogous to classical
      forward genetic approaches except that it operates directly at the protein level.
      This approach led to the identification of integrin-binding agonist antibodies
      that efficiently converted human stem cells to dendritic cells. 

PMID- 23980155
TI  - Correlating preclinical animal studies and human clinical trials of a
      multifunctional, polymeric nanoparticle.
AB  - Nanoparticles are currently being investigated in a number of human clinical
      trials. As information on how nanoparticles function in humans is difficult to
      obtain, animal studies that can be correlative to human behavior are needed to
      provide guidance for human clinical trials. Here, we report correlative studies
      on animals and humans for CRLX101, a 20- to 30-nm-diameter, multifunctional,
      polymeric nanoparticle containing camptothecin (CPT). CRLX101 is currently in
      phase 2 clinical trials, and human data from several of the clinical
      investigations are compared with results from multispecies animal studies. The
      pharmacokinetics of polymer-conjugated CPT (indicative of the CRLX101
      nanoparticles) in mice, rats, dogs, and humans reveal that the area under the
      curve scales linearly with milligrams of CPT per square meter for all species.
      Plasma concentrations of unconjugated CPT released from CRLX101 in animals and
      humans are consistent with each other after accounting for differences in serum
      albumin binding of CPT. Urinary excretion of polymer-conjugated CPT occurs
      primarily within the initial 24 h after dosing in animals and humans. The urinary
      excretion dynamics of polymer-conjugated and unconjugated CPT appear similar
      between animals and humans. CRLX101 accumulates into solid tumors and releases
      CPT over a period of several days to give inhibition of its target in animal
      xenograft models of cancer and in the tumors of humans. Taken in total, the
      evidence provided from animal models on the CRLX101 mechanism of action suggests
      that the behavior of CRLX101 in animals is translatable to humans. 

PMID- 23980156
TI  - Lessons from application of the UNRES force field to predictions of structures of
      CASP10 targets.
AB  - The performance of the physics-based protocol, whose main component is the United
      Residue (UNRES) physics-based coarse-grained force field, developed in our
      laboratory for the prediction of protein structure from amino acid sequence, is
      illustrated. Candidate models are selected, based on probabilities of the
      conformational families determined by multiplexed replica-exchange simulations,
      from the 10th Community Wide Experiment on the Critical Assessment of Techniques
      for Protein Structure Prediction (CASP10). For target T0663, classified as a new
      fold, which consists of two domains homologous to those of known proteins, UNRES
      predicted the correct symmetry of packing, in which the domains are rotated with
      respect to each other by 180 degrees  in the experimental structure. By contrast,
      models obtained by knowledge-based methods, in which each domain is modeled very
      accurately but not rotated, resulted in incorrect packing. Two UNRES models of
      this target were featured by the assessors. Correct domain packing was also
      predicted by UNRES for the homologous target T0644, which has a similar structure
      to that of T0663, except that the two domains are not rotated. Predictions for
      two other targets, T0668 and T0684_D2, are among the best ones by global distance
      test score. These results suggest that our physics-based method has substantial
      predictive power. In particular, it has the ability to predict domain-domain
      orientations, which is a significant advance in the state of the art. 

PMID- 23980157
TI  - H3R42me2a is a histone modification with positive transcriptional effects.
AB  - Histone posttranslational modification leads to downstream effects indirectly by
      allowing or preventing docking of effector molecules, or directly by changing the
      intrinsic biophysical properties of local chromatin. To date, little has been
      done to study posttranslational modifications that lie outside of the
      unstructured tail domains of histones. Core residues, and in particular arginines
      in H3 and H4, mediate key interactions between the histone octamer and DNA in
      forming the nucleosomal particle. Using mass spectrometry, we find that one of
      these core residues, arginine 42 of histone H3 (H3R42), is dimethylated in
      mammalian cells by the methyltransferases coactivator arginine methyltransferase
      1 (CARM1) and protein arginine methyltransferase 6 (PRMT6) in vitro and in vivo,
      and we demonstrate that methylation of H3R42 stimulates transcription in vitro
      from chromatinized templates. Thus, H3R42 is a new, "nontail" histone methylation
      site with positive effects on transcription. We propose that methylation of basic
      histone residues at the DNA interface may disrupt histone:DNA interactions, with
      effects on downstream processes, notably transcription. 

PMID- 23980152
TI  - Complement modulates the cutaneous microbiome and inflammatory milieu.
AB  - The skin is colonized by a plethora of microbes that include commensals and
      potential pathogens, but it is currently unknown how cutaneous host immune
      mechanisms influence the composition, diversity, and quantity of the skin
      microbiota. Here we reveal an interactive role for complement in cutaneous host
      microbiome interactions. Inhibiting signaling of the complement component C5a
      receptor (C5aR) altered the composition and diversity of the skin microbiota as
      revealed by deep sequencing of the bacterial 16S rRNA gene. In parallel, we
      demonstrate that C5aR inhibition results in down-regulation of genes encoding
      cutaneous antimicrobial peptides, pattern recognition receptors, and
      proinflammatory mediators. Immunohistochemistry of inflammatory cell infiltrates
      in the skin showed reduced numbers of macrophages and lymphocytes with C5aR
      inhibition. Further, comparing cutaneous gene expression in germ-free mice vs.
      conventionally raised mice suggests that the commensal microbiota regulates
      expression of complement genes in the skin. These findings demonstrate a
      component of host immunity that impacts colonization of the skin by the commensal
      microbiota and vice versa, a critical step toward understanding host-microbe
      immune mutualism of the skin and its implications for health and disease.
      Additionally, we reveal a role for complement in homeostatic host-microbiome
      interactions of the skin. 

PMID- 23980158
TI  - Quantitative basis for neuroimaging of cortical laminae with calibrated
      functional MRI.
AB  - Layer-specific neurophysiologic, hemodynamic, and metabolic measurements are
      needed to interpret high-resolution functional magnetic resonance imaging (fMRI)
      data in the cerebral cortex. We examined how neurovascular and neurometabolic
      couplings vary vertically in the rat's somatosensory cortex. During sensory
      stimulation we measured dynamic layer-specific responses of local field potential
      (LFP) and multiunit activity (MUA) as well as blood oxygenation level-dependent
      (BOLD) signal and cerebral blood volume (CBV) and blood flow (CBF), which in turn
      were used to calculate changes in oxidative metabolism (CMR(O2)) with calibrated
      fMRI. Both BOLD signal and CBV decreased from superficial to deep laminae, but
      these responses were not well correlated with either layer-specific LFP or MUA.
      However, CBF changes were quite stable across laminae, similar to LFP. However,
      changes in CMR(O2) and MUA varied across cortex in a correlated manner and both
      were reduced in superficial lamina. These results lay the framework for
      quantitative neuroimaging across cortical laminae with calibrated fMRI methods.

PMID- 23980159
TI  - Protoribosome by quantum kernel energy method.
AB  - Experimental evidence suggests the existence of an RNA molecular prebiotic
      entity, called by us the "protoribosome," which may have evolved in the RNA world
      before evolution of the genetic code and proteins. This vestige of the RNA world,
      which possesses all of the capabilities required for peptide bond formation,
      seems to be still functioning in the heart of all of the contemporary ribosome.
      Within the modern ribosome this remnant includes the peptidyl transferase center.
      Its highly conserved nucleotide sequence is suggestive of its robustness under
      diverse environmental conditions, and hence on its prebiotic origin. Its twofold
      pseudosymmetry suggests that this entity could have been a dimer of self-folding
      RNA units that formed a pocket within which two activated amino acids might be
      accommodated, similar to the binding mode of modern tRNA molecules that carry
      amino acids or peptidyl moieties. Using quantum mechanics and crystal
      coordinates, this work studies the question of whether the putative protoribosome
      has properties necessary to function as an evolutionary precursor to the modern
      ribosome. The quantum model used in the calculations is density functional theory
      -B3LYP/3-21G*, implemented using the kernel energy method to make the
      computations practical and efficient. It occurs that the necessary conditions
      that would characterize a practicable protoribosome--namely (i) energetic
      structural stability and (ii) energetically stable attachment to substrates--are
      both well satisfied.

PMID- 23980160
TI  - Eddy current and coupled landscapes for nonadiabatic and nonequilibrium complex
      system dynamics.
AB  - Physical and biological systems are often involved with coupled processes of
      different time scales. In the system with electronic and atomic motions, for
      example, the interplay between the atomic motion along the same energy landscape
      and the electronic hopping between different landscapes is critical: the system
      behavior largely depends on whether the intralandscape motion is slower
      (adiabatic) or faster (nonadiabatic) than the interlandscape hopping. For general
      nonequilibrium dynamics where Hamiltonian or energy function is unknown a priori,
      the challenge is how to extend the concepts of the intra- and interlandscape
      dynamics. In this paper we establish a theoretical framework for describing
      global nonequilibrium and nonadiabatic complex system dynamics by transforming
      the coupled landscapes into a single landscape but with additional dimensions. On
      this single landscape, dynamics is driven by gradient of the potential landscape,
      which is closely related to the steady-state probability distribution of the
      enlarged dimensions, and the probability flux, which has a curl nature. Through
      an example of a self-regulating gene circuit, we show that the curl flux has
      dramatic effects on gene regulatory dynamics. The curl flux and landscape
      framework developed here are easy to visualize and can be used to guide further
      investigation of physical and biological nonequilibrium systems. 

PMID- 23980161
TI  - Emphasis of spatial cues in the temporal fine structure during the rising
      segments of amplitude-modulated sounds.
AB  - The ability to locate the direction of a target sound in a background of
      competing sources is critical to the survival of many species and important for
      human communication. Nevertheless, brain mechanisms that provide for such
      accurate localization abilities remain poorly understood. In particular, it
      remains unclear how the auditory brain is able to extract reliable spatial
      information directly from the source when competing sounds and reflections
      dominate all but the earliest moments of the sound wave reaching each ear. We
      developed a stimulus mimicking the mutual relationship of sound amplitude and
      binaural cues, characteristic to reverberant speech. This stimulus, named
      amplitude modulated binaural beat, allows for a parametric and isolated change of
      modulation frequency and phase relations. Employing magnetoencephalography and
      psychoacoustics it is demonstrated that the auditory brain uses binaural
      information in the stimulus fine structure only during the rising portion of each
      modulation cycle, rendering spatial information recoverable in an otherwise
      unlocalizable sound. The data suggest that amplitude modulation provides a means
      of "glimpsing" low-frequency spatial cues in a manner that benefits listening in
      noisy or reverberant environments. 

PMID- 23980162
TI  - Cone photoreceptor types in zebrafish are generated by symmetric terminal
      divisions of dedicated precursors.
AB  - Proper functioning of sensory systems requires the generation of appropriate
      numbers and proportions of neuronal subtypes that encode distinct information.
      Perception of color relies on signals from multiple cone photoreceptor types. In
      cone-dominated retinas, each cone expresses a single opsin type with peak
      sensitivity to UV, long (L) (red), medium (M) (green), or short (S) (blue)
      wavelengths. The modes of cell division generating distinct cone types are
      unknown. We report here a mechanism whereby zebrafish cone photoreceptors of the
      same type are produced by symmetric division of dedicated precursors. Transgenic
      fish in which the thyroid hormone receptor beta2 (trbeta2) promoter drives
      fluorescent protein expression before L-cone precursors themselves are produced
      permitted tracking of their division in vivo. Every L cone in a local region
      resulted from the terminal division of an L-cone precursor, suggesting that such
      divisions contribute significantly to L-cone production. Analysis of the fate of
      isolated pairs of cones and time-lapse observations suggest that other cone types
      can also arise by symmetric terminal divisions. Such divisions of dedicated
      precursors may help to rapidly attain the final numbers and proportions of cone
      types (L > M, UV > S) in zebrafish larvae. Loss- and gain-of-function experiments
      show that L-opsin expression requires trbeta2 activity before cone
      differentiation. Ectopic expression of trbeta2 after cone differentiation
      produces cones with mixed opsins. Temporal differences in the onset of trbeta2
      expression could explain why some species have mixed, and others have pure, cone
      types. 

PMID- 23980163
TI  - Overlapping gene coexpression patterns in human medullary thymic epithelial cells
      generate self-antigen diversity.
AB  - Promiscuous expression of numerous tissue-restricted self-antigens (TRAs) in
      medullary thymic epithelial cells (mTECs) is essential to safeguard self
      tolerance. A distinct feature of promiscuous gene expression is its mosaic
      pattern (i.e., at a given time, each self-antigen is expressed only in 1-3% of
      mTECs). How this mosaic pattern is generated at the single-cell level is
      currently not understood. Here, we show that subsets of human mTECs expressing a
      particular TRA coexpress distinct sets of genes. We identified three coexpression
      groups comprising overlapping and complementary gene sets, which preferentially
      mapped to certain chromosomes and intrachromosomal gene clusters. Coexpressed
      gene loci tended to colocalize to the same nuclear subdomain. The TRA subsets
      aligned along progressive differentiation stages within the mature mTEC subset
      and, in vitro, interconverted along this sequence. Our data suggest that single
      mTECs shift through distinct gene pools, thus scanning a sizeable fraction of the
      overall repertoire of promiscuously expressed self-antigens. These findings have
      implications for the temporal and spatial (re)presentation of self-antigens in
      the medulla in the context of tolerance induction. 

PMID- 23980164
TI  - Comprehensive experimental fitness landscape and evolutionary network for small
      RNA.
AB  - The origin of life is believed to have progressed through an RNA world, in which
      RNA acted as both genetic material and functional molecules. The structure of the
      evolutionary fitness landscape of RNA would determine natural selection for the
      first functional sequences. Fitness landscapes are the subject of much
      speculation, but their structure is essentially unknown. Here we describe a
      comprehensive map of a fitness landscape, exploring nearly all of sequence space,
      for short RNAs surviving selection in vitro. With the exception of a small
      evolutionary network, we find that fitness peaks are largely isolated from one
      another, highlighting the importance of historical contingency and indicating
      that natural selection would be constrained to local exploration in the RNA
      world. 

PMID- 23980165
TI  - US studies may overestimate effect sizes in softer research.
AB  - Many biases affect scientific research, causing a waste of resources, posing a
      threat to human health, and hampering scientific progress. These problems are
      hypothesized to be worsened by lack of consensus on theories and methods, by
      selective publication processes, and by career systems too heavily oriented
      toward productivity, such as those adopted in the United States (US). Here, we
      extracted 1,174 primary outcomes appearing in 82 meta-analyses published in
      health-related biological and behavioral research sampled from the Web of Science
      categories Genetics & Heredity and Psychiatry and measured how individual results
      deviated from the overall summary effect size within their respective meta
      analysis. We found that primary studies whose outcome included behavioral
      parameters were generally more likely to report extreme effects, and those with a
      corresponding author based in the US were more likely to deviate in the direction
      predicted by their experimental hypotheses, particularly when their outcome did
      not include additional biological parameters. Nonbehavioral studies showed no
      such "US effect" and were subject mainly to sampling variance and small-study
      effects, which were stronger for non-US countries. Although this latter finding
      could be interpreted as a publication bias against non-US authors, the US effect
      observed in behavioral research is unlikely to be generated by editorial biases.
      Behavioral studies have lower methodological consensus and higher noise, making
      US researchers potentially more likely to express an underlying propensity to
      report strong and significant findings. 

PMID- 23980166
TI  - Impact of a single base pair substitution on the charge transfer rate along short
      DNA hairpins.
AB  - Numerical studies of hole migration along short DNA hairpins were performed with
      a particular emphasis on the variations of the rate and quantum yield of the
      charge separation process with the location of a single guanine:cytosine (G:C)
      base pair. Our calculations show that the hole arrival rate increases as the
      position of the guanine:cytosine base pair shifts from the beginning to the end
      of the sequence. Although these results are in agreement with recent experimental
      findings, the mechanism governing the charge migration along these sequences is
      revisited here. Instead of the phenomenological two-step hopping mechanism via
      the guanine base, the charge propagation occurs through a delocalization of the
      hole density along the base pair stack. Furthermore, the variations of the charge
      transfer with the position of the guanine base are explained by the impact of the
      base pair substitutions on the delocalized conduction channels. 

PMID- 23980167
TI  - SIRT1 regulates adaptive response of the growth hormone--insulin-like growth
      factor-I axis under fasting conditions in liver.
AB  - Adaptation under fasting conditions is critical for survival in animals. Sirtuin
      1 (SIRT1), a protein deacetylase, plays an essential role in adaptive metabolic
      and endocrine responses under fasting conditions by modifying the acetylation
      status of various proteins. Fasting induces growth hormone (GH) resistance in the
      liver, leading to decreased serum insulin-like growth factor-I (IGF-I) levels as
      an endocrine adaptation for malnutrition; however, the underlying mechanisms of
      this action remain to be fully elucidated. Here we report that in vivo knockdown
      of SIRT1 in the liver restored the fasting-induced decrease in serum IGF-I levels
      and enhanced the GH-dependent increase in IGF-I levels, indicating that SIRT1
      negatively regulates GH-dependent IGF-I production in the liver. In vitro
      analysis using hepatocytes demonstrated that SIRT1 suppresses GH-dependent IGF-I
      expression, accompanied by decreased tyrosine phosphorylation on signal
      transducer and activator of transcription (STAT) 5. GST pull-down assays revealed
      that SIRT1 interacts directly with STAT5. When the lysine residues adjacent to
      the SH2 domain of STAT5 were mutated, STAT5 acetylation decreased concomitant
      with a decrease in its transcriptional activity. Knockdown of SIRT1 enhanced the
      acetylation and GH-induced tyrosine phosphorylation of STAT5, as well as the GH
      induced interaction of the GH receptor with STAT5. These data indicate that SIRT1
      negatively regulates GH-induced STAT5 phosphorylation and IGF-I production via
      deacetylation of STAT5 in the liver. In addition, our findings explain the
      underlying mechanisms of GH resistance under fasting conditions, which is a known
      element of endocrine adaptation during fasting. 

PMID- 23980168
TI  - Natalisin, a tachykinin-like signaling system, regulates sexual activity and
      fecundity in insects.
AB  - An arthropod-specific peptidergic system, the neuropeptide designated here as
      natalisin and its receptor, was identified and investigated in three
      holometabolous insect species: Drosophila melanogaster, Tribolium castaneum, and
      Bombyx mori. In all three species, natalisin expression was observed in 3-4 pairs
      of the brain neurons: the anterior dorso-lateral interneurons, inferior
      contralateral interneurons, and small pars intercerebralis neurons. In B. mori,
      natalisin also was expressed in two additional pairs of contralateral
      interneurons in the subesophageal ganglion. Natalisin-RNAi and the activation or
      silencing of the neural activities in the natalisin-specific cells in D.
      melanogaster induced significant defects in the mating behaviors of both males
      and females. Knockdown of natalisin expression in T. castaneum resulted in
      significant reduction in the fecundity. The similarity of the natalisin C
      terminal motifs to those of vertebrate tachykinins and of tachykinin-related
      peptides in arthropods led us to identify the natalisin receptor. A G protein
      coupled receptor, previously known as tachykinin receptor 86C (also known as the
      neurokinin K receptor of D. melanogaster), now has been recognized as a bona fide
      natalisin receptor. Taken together, the taxonomic distribution pattern of the
      natalisin gene and the phylogeny of the receptor suggest that natalisin is an
      ancestral sibling of tachykinin that evolved only in the arthropod lineage. 

PMID- 23980169
TI  - In vivo imaging of alphaherpesvirus infection reveals synchronized activity
      dependent on axonal sorting of viral proteins.
AB  - A clinical hallmark of human alphaherpesvirus infections is peripheral pain or
      itching. Pseudorabies virus (PRV), a broad host range alphaherpesvirus, causes
      violent pruritus in many different animals, but the mechanism is unknown.
      Previous in vitro studies have shown that infected, cultured peripheral nervous
      system (PNS) neurons exhibited aberrant electrical activity after PRV infection
      due to the action of viral membrane fusion proteins, yet it is unclear if such
      activity occurs in infected PNS ganglia in living animals and if it correlates
      with disease symptoms. Using two-photon microscopy, we imaged autonomic ganglia
      in living mice infected with PRV strains expressing GCaMP3, a genetically encoded
      calcium indicator, and used the changes in calcium flux to monitor the activity
      of many neurons simultaneously with single-cell resolution. Infection with
      virulent PRV caused these PNS neurons to fire synchronously and cyclically in
      highly correlated patterns among infected neurons. This activity persisted even
      when we severed the presynaptic axons, showing that infection-induced firing is
      independent of input from presynaptic brainstem neurons. This activity was not
      observed after infections with an attenuated PRV recombinant used for circuit
      tracing or with PRV mutants lacking either viral glycoprotein B, required for
      membrane fusion, or viral membrane protein Us9, required for sorting virions and
      viral glycoproteins into axons. We propose that the viral fusion proteins
      produced by virulent PRV infection induce electrical coupling in unmyelinated
      axons in vivo. This action would then give rise to the synchronous and cyclical
      activity in the ganglia and contribute to the characteristic peripheral
      neuropathy. 

PMID- 23980170
TI  - Structural insights into the interaction of IL-33 with its receptors.
AB  - Interleukin (IL)-33 is an important member of the IL-1 family that has
      pleiotropic activities in innate and adaptive immune responses in host defense
      and disease. It signals through its ligand-binding primary receptor ST2 and IL-1
      receptor accessory protein (IL-1RAcP), both of which are members of the IL-1
      receptor family. To clarify the interaction of IL-33 with its receptors, we
      determined the crystal structure of IL-33 in complex with the ectodomain of ST2
      at a resolution of 3.27 A. Coupled with structure-based mutagenesis and binding
      assay, the structural results define the molecular mechanism by which ST2
      specifically recognizes IL-33. Structural comparison with other ligand-receptor
      complexes in the IL-1 family indicates that surface-charge complementarity is
      critical in determining ligand-binding specificity of IL-1 primary receptors.
      Combined crystallography and small-angle X-ray-scattering studies reveal that ST2
      possesses hinge flexibility between the D3 domain and D1D2 module, whereas IL
      1RAcP exhibits a rigid conformation in the unbound state in solution. The
      molecular flexibility of ST2 provides structural insights into domain-level
      conformational change of IL-1 primary receptors upon ligand binding, and the
      rigidity of IL-1RAcP explains its inability to bind ligands directly. The
      solution architecture of IL-33-ST2-IL-1RAcP complex from small-angle X-ray
      scattering analysis resembles IL-1beta-IL-1RII-IL-1RAcP and IL-1beta-IL-1RI-IL
      1RAcP crystal structures. The collective results confer IL-33 structure-function
      relationships, supporting and extending a general model for ligand-receptor
      assembly and activation in the IL-1 family. 

PMID- 23980171
TI  - The transcription factor Interferon Regulatory Factor 4 is required for the
      generation of protective effector CD8+ T cells.
AB  - Robust cytotoxic CD8(+) T-cell response is important for immunity to
      intracellular pathogens. Here, we show that the transcription factor IFN
      Regulatory Factor 4 (IRF4) is crucial for the protective CD8(+) T-cell response
      to the intracellular bacterium Listeria monocytogenes. IRF4-deficient (Irf4(-/-))
      mice could not clear L. monocytogenes infection and generated decreased numbers
      of L. monocytogenes-specific CD8(+) T cells with impaired effector phenotype and
      function. Transfer of wild-type CD8(+) T cells into Irf4(-/-) mice improved
      bacterial clearance, suggesting an intrinsic defect of CD8(+) T cells in Irf4(-/
      ) mice. Following transfer into wild-type recipients, Irf4(-/-) CD8(+) T cells
      became activated and showed initial proliferation upon L. monocytogenes
      infection. However, these cells could not sustain proliferation, produced reduced
      amounts of IFN-gamma and TNF-alpha, and failed to acquire cytotoxic function.
      Forced IRF4 expression in Irf4(-/-) CD8(+) T cells rescued the defect. During
      acute infection, Irf4(-/-) CD8(+) T cells demonstrated diminished expression of B
      lymphocyte-induced maturation protein-1 (Blimp-1), inhibitor of DNA binding
      (Id)2, and T-box expressed in T cells (T-bet), transcription factors programming
      effector-cell generation. IRF4 was essential for expression of Blimp-1,
      suggesting that altered regulation of Blimp-1 contributes to the defects of Irf4(
      /-) CD8(+) T cells. Despite increased levels of B-cell lymphoma 6 (BCL-6),
      Eomesodermin, and Id3, Irf4(-/-) CD8(+) T cells showed impaired memory-cell
      formation, indicating additional functions for IRF4 in this process. As IRF4
      governs B-cell and CD4(+) T-cell differentiation, the identification of its
      decisive role in peripheral CD8(+) T-cell differentiation, suggests a common
      regulatory function for IRF4 in adaptive lymphocytes fate decision. 

PMID- 23980172
TI  - Immunotherapy of chronic hepatitis C virus infection with antibodies against
      programmed cell death-1 (PD-1).
AB  - Hepatitis C virus (HCV) persistence is facilitated by exhaustion of CD8+ T cells
      that express the inhibitory receptor programmed cell death 1 (PD-1). Blockade of
      PD-1 signaling improves in vitro proliferation of HCV-specific T lymphocytes, but
      whether antiviral function can be restored in infected individuals is unknown. To
      address this question, chimpanzees with persistent HCV infection were treated
      with anti-PD-1 antibodies. A significant reduction in HCV viremia was observed in
      one of three treated animals without apparent hepatocellular injury. Viremia
      rebounded in the responder animal when antibody treatment was discontinued.
      Control of HCV replication was associated with restoration of intrahepatic CD4+
      and CD8+ T-cell immunity against multiple HCV proteins. The responder animal had
      a history of broader T-cell immunity to multiple HCV proteins than the two
      chimpanzees that did not respond to PD-1 therapy. The results suggest that
      successful PD-1 blockade likely requires a critical threshold of preexisting
      virus-specific T cells in liver and warrants consideration of therapeutic
      vaccination strategies in combination with PD-1 blockade to broaden narrow
      responses. Anti-PD-1 immunotherapy may also facilitate control of other
      persistent viruses, notably the hepatitis B virus where options for long-term
      control of virus replication are limited. 

PMID- 23980173
TI  - Structure of the transition state for the binding of c-Myb and KIX highlights an
      unexpected order for a disordered system.
AB  - A classical dogma of molecular biology dictates that the 3D structure of a
      protein is necessary for its function. However, a considerable fraction of the
      human proteome, although functional, does not adopt a defined folded state under
      physiological conditions. These intrinsically disordered proteins tend to fold
      upon binding to their partners with a molecular mechanism that is elusive to
      experimental characterization. Indeed, although many hypotheses have been put
      forward, the functional role (if any) of disorder in these intrinsically
      denatured systems is still shrouded in mystery. Here, we characterize the
      structure of the transition state of the binding-induced folding in the reaction
      between the KIX domain of the CREB-binding protein and the transactivation domain
      of c-Myb. The analysis, based on the characterization of a series of conservative
      site-directed mutants, reveals a very high content of native-like structure in
      the transition state and indicates that the recognition between KIX and c-Myb is
      geometrically precise. The implications of our results in the light of previous
      work on intrinsically unstructured systems are discussed. 

PMID- 23980174
TI  - Definition of a third VLR gene in hagfish.
AB  - Jawless vertebrates (cyclostomes) have an alternative adaptive immune system in
      which lymphocytes somatically diversify their variable lymphocyte receptors (VLR)
      through recombinatorial use of leucine-rich repeat cassettes during VLR gene
      assembly. Three types of these anticipatory receptors in lampreys (VLRA, VLRB,
      and VLRC) are expressed by separate lymphocyte lineages. However, only two VLR
      genes (VLRA and VLRB) have been found in hagfish. Here we have identified a third
      hagfish VLR, which undergoes somatic assembly to generate sufficient diversity to
      encode a large repertoire of anticipatory receptors. Sequence analysis,
      structural comparison, and phylogenetic analysis indicate that the unique hagfish
      VLR is the counterpart of lamprey VLRA and the previously identified hagfish
      "VLRA" is the lamprey VLRC counterpart. The demonstration of three orthologous
      VLR genes in both lampreys and hagfish suggests that this anticipatory receptor
      system evolved in a common ancestor of the two cyclostome lineages around 480
      Mya. 

PMID- 23980175
TI  - ERK signaling couples nutrient status to antiviral defense in the insect gut.
AB  - A unique facet of arthropod-borne virus (arbovirus) infection is that the
      pathogens are orally acquired by an insect vector during the taking of a blood
      meal, which directly links nutrient acquisition and pathogen challenge. We show
      that the nutrient responsive ERK pathway is both induced by and restricts
      disparate arboviruses in Drosophila intestines, providing insight into the
      molecular determinants of the antiviral "midgut barrier." Wild-type flies are
      refractory to oral infection by arboviruses, including Sindbis virus and
      vesicular stomatitis virus, but this innate restriction can be overcome
      chemically by oral administration of an ERK pathway inhibitor or genetically via
      the specific loss of ERK in Drosophila intestinal epithelial cells. In addition,
      we found that vertebrate insulin, which activates ERK in the mosquito gut during
      a blood meal, restricts viral infection in Drosophila cells and against viral
      invasion of the insect gut epithelium. We find that ERK's antiviral signaling
      activity is likely conserved in Aedes mosquitoes, because genetic or
      pharmacologic manipulation of the ERK pathway affects viral infection of mosquito
      cells. These studies demonstrate that ERK signaling has a broadly antiviral role
      in insects and suggest that insects take advantage of cross-species signals in
      the meal to trigger antiviral immunity. 

PMID- 23980176
TI  - Bidirectional communication between oocytes and ovarian follicular somatic cells
      is required for meiotic arrest of mammalian oocytes.
AB  - Coordinated regulation of oocyte and ovarian follicular development is essential
      for fertility. In particular, the progression of meiosis, a germ cell-specific
      cell division that reduces the number of chromosomes from diploid to haploid,
      must be arrested until just before ovulation. Follicular somatic cells are well
      known to impose this arrest, which is essential for oocyte-follicle developmental
      synchrony. Follicular somatic cells sustain meiotic arrest via the natriuretic
      peptide C/natriuretic peptide receptor 2 (NPPC/NPR2) system, and possibly also
      via high levels of the purine hypoxanthine in the follicular fluid. Upon
      activation by the ligand NPPC, NPR2, the predominant guanylyl cyclase in
      follicular somatic cells, produces cyclic guanosine monophosphate (cGMP), which
      maintains meiotic arrest after transfer to the oocyte via gap junctions. Here we
      report that both the NPPC/NPR2 system and hypoxanthine require the activity of
      inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme required
      for the production of guanylyl metabolites and cGMP. Furthermore, oocyte-derived
      paracrine factors, particularly the growth differentiation factor 9-bone
      morphogenetic protein 15 heterodimer, promote expression of Impdh and Npr2 and
      elevate cGMP levels in cumulus cells. Thus, although the somatic compartment of
      ovarian follicles plays an essential role in the maintenance of oocyte meiotic
      arrest, as has been known for many years, this function of the somatic cells is
      surprisingly regulated by signals from the oocyte itself. 

PMID- 23980177
TI  - An unusual CsrA family member operates in series with RsmA to amplify
      posttranscriptional responses in Pseudomonas aeruginosa.
AB  - Members of the CsrA family of prokaryotic mRNA-binding proteins alter the
      translation and/or stability of transcripts needed for numerous global
      physiological processes. The previously described CsrA family member in
      Pseudomonas aeruginosa (RsmA) plays a central role in determining infection
      modality by reciprocally regulating processes associated with acute (type III
      secretion and motility) and chronic (type VI secretion and biofilm formation)
      infection. Here we describe a second, structurally distinct RsmA homolog in P.
      aeruginosa (RsmF) that has an overlapping yet unique regulatory role. RsmF
      deviates from the canonical 5 beta-strand and carboxyl-terminal alpha-helix
      topology of all other CsrA proteins by having the alpha-helix internally
      positioned. Despite striking changes in topology, RsmF adopts a tertiary
      structure similar to other CsrA family members and binds a subset of RsmA mRNA
      targets, suggesting that RsmF activity is mediated through a conserved mechanism
      of RNA recognition. Whereas deletion of rsmF alone had little effect on RsmA
      regulated processes, strains lacking both rsmA and rsmF exhibited enhanced RsmA
      phenotypes for markers of both type III and type VI secretion systems. In
      addition, simultaneous deletion of rsmA and rsmF resulted in superior biofilm
      formation relative to the wild-type or rsmA strains. We show that RsmF
      translation is derepressed in an rsmA mutant and demonstrate that RsmA
      specifically binds to rsmF mRNA in vitro, creating a global hierarchical
      regulatory cascade that operates at the posttranscriptional level. 

PMID- 23980178
TI  - Role of activity-dependent BDNF expression in hippocampal-prefrontal cortical
      regulation of behavioral perseverance.
AB  - Activity-dependent gene transcription, including that of the brain-derived
      neurotrophic factor (Bdnf) gene, has been implicated in various cognitive
      functions. We previously demonstrated that mutant mice with selective disruption
      of activity-dependent BDNF expression (BDNF-KIV mice) exhibit deficits in GABA
      mediated inhibition in the prefrontal cortex (PFC). Here, we show that disruption
      of activity-dependent BDNF expression impairs BDNF-dependent late-phase long-term
      potentiation (L-LTP) in CA1, a site of hippocampal output to the PFC.
      Interestingly, early-phase LTP and conventional L-LTP induced by strong tetanic
      stimulation were completely normal in BDNF-KIV mice. In parallel, attenuation of
      activity-dependent BDNF expression significantly impairs spatial memory reversal
      and contextual memory extinction, two executive functions that require intact
      hippocampal-PFC circuitry. In contrast, spatial and contextual memory per se were
      not affected. Thus, activity-dependent BDNF expression in the hippocampus and PFC
      may contribute to cognitive and behavioral flexibility. These results suggest
      distinct roles for different forms of L-LTP and provide a link between activity
      dependent BDNF expression and behavioral perseverance, a hallmark of several
      psychiatric disorders. 

PMID- 23980179
TI  - Arginase regulates red blood cell nitric oxide synthase and export of
      cardioprotective nitric oxide bioactivity.
AB  - The theory that red blood cells (RBCs) generate and release nitric oxide (NO)
      like bioactivity has gained considerable interest. However, it remains unclear
      whether it can be produced by endothelial NO synthase (eNOS), which is present in
      RBCs, and whether NO can escape scavenging by hemoglobin. The aim of this study
      was to test the hypothesis that arginase reciprocally controls NO formation in
      RBCs by competition with eNOS for their common substrate arginine and that RBC
      derived NO is functionally active following arginase blockade. We show that
      rodent and human RBCs contain functional arginase 1 and that pharmacological
      inhibition of arginase increases export of eNOS-derived nitrogen oxides from RBCs
      under basal conditions. The functional importance was tested in an ex vivo model
      of myocardial ischemia-reperfusion injury. Inhibitors of arginase significantly
      improved postischemic functional recovery in rat hearts if administered in whole
      blood or with RBCs in plasma. By contrast, arginase inhibition did not improve
      postischemic recovery when administered with buffer solution or plasma alone. The
      protective effect of arginase inhibition was lost in the presence of a NOS
      inhibitor. Moreover, hearts from eNOS(-/-) mice were protected when the arginase
      inhibitor was given with blood from wild-type donors. In contrast, when hearts
      from wild-type mice were given blood from eNOS(-/-) mice, the arginase inhibitor
      failed to protect against ischemia-reperfusion. These results strongly support
      the notion that RBCs contain functional eNOS and release NO-like bioactivity.
      This process is under tight control by arginase 1 and is of functional importance
      during ischemia-reperfusion. 

PMID- 23980180
TI  - Coherent delta-band oscillations between cortical areas correlate with decision
      making.
AB  - Coherent oscillations in the theta-to-gamma frequency range have been proposed as
      a mechanism that coordinates neural activity in large-scale cortical networks in
      sensory, motor, and cognitive tasks. Whether this mechanism also involves
      coherent oscillations at delta frequencies (1-4 Hz) is not known. Rather, delta
      oscillations have been associated with slow-wave sleep. Here, we show coherent
      oscillations in the delta frequency band between parietal and frontal cortices
      during the decision-making component of a somatosensory discrimination task.
      Importantly, the magnitude of this delta-band coherence is modulated by the
      different decision alternatives. Furthermore, during control conditions not
      requiring decision making, delta-band coherences are typically much reduced. Our
      work indicates an important role for synchronous activity in the delta frequency
      band when large-scale, distant cortical networks coordinate their neural activity
      during decision making. 

PMID- 23980181
TI  - Burkholderia pseudomallei suppresses Caenorhabditis elegans immunity by specific
      degradation of a GATA transcription factor.
AB  - Burkholderia pseudomallei is a Gram-negative soil bacterium that infects both
      humans and animals. Although cell culture studies have revealed significant
      insights into factors contributing to virulence and host defense, the
      interactions between this pathogen and its intact host remain to be elucidated.
      To gain insights into the host defense responses to B. pseudomallei infection
      within an intact host, we analyzed the genome-wide transcriptome of infected
      Caenorhabditis elegans and identified ~6% of the nematode genes that were
      significantly altered over a 12-h course of infection. An unexpected feature of
      the transcriptional response to B. pseudomallei was a progressive increase in the
      proportion of down-regulated genes, of which ELT-2 transcriptional targets were
      significantly enriched. ELT-2 is an intestinal GATA transcription factor with a
      conserved role in immune responses. We demonstrate that B. pseudomallei down
      regulation of ELT-2 targets is associated with degradation of ELT-2 protein by
      the host ubiquitin-proteasome system. Degradation of ELT-2 requires the B.
      pseudomallei type III secretion system. Together, our studies using an intact
      host provide evidence for pathogen-mediated host immune suppression through the
      destruction of a host transcription factor. 

PMID- 23980182
TI  - Huntington disease arises from a combinatory toxicity of polyglutamine and copper
      binding.
AB  - Huntington disease (HD) is a progressive neurodegenerative disorder caused by
      dominant polyglutamine (polyQ) expansion within the N terminus of huntingtin
      (Htt) protein. Abnormal metal accumulation in the striatum of HD patients has
      been reported for many years, but a causative relationship has not yet been
      established. Furthermore, if metal is indeed involved in HD, the underlying
      mechanism needs to be explored. Here using a Drosophila model of HD, wherein Htt
      exon1 with expanded polyQ (Htt exon1-polyQ) is introduced, we show that altered
      expression of genes involved in copper metabolism significantly modulates the HD
      progression. Intervention of dietary copper levels also modifies HD phenotypes in
      the fly. Copper reduction to a large extent decreases the level of oligomerized
      and aggregated Htt. Strikingly, substitution of two potential copper-binding
      residues of Htt, Met8 and His82, completely dissociates the copper-intensifying
      toxicity of Htt exon1-polyQ. Our results therefore indicate HD entails two levels
      of toxicity: the copper-facilitated protein aggregation as conferred by a direct
      copper binding in the exon1 and the copper-independent polyQ toxicity. The
      existence of these two parallel pathways converging into Htt toxicity also
      suggests that an ideal HD therapy would be a multipronged approach that takes
      both these actions into consideration. 

PMID- 23980184
TI  - Spin-dependent electron transmission through bacteriorhodopsin embedded in purple
      membrane.
AB  - Spin-dependent photoelectron transmission and spin-dependent electrochemical
      studies were conducted on purple membrane containing bacteriorhodopsin (bR)
      deposited on gold, aluminum/aluminum-oxide, and nickel substrates. The result
      indicates spin selectivity in electron transmission through the membrane.
      Although the chiral bR occupies only about 10% of the volume of the membrane, the
      spin polarization found is on the order of 15%. The electrochemical studies
      indicate a strong dependence of the conduction on the protein's structure.
      Denaturation of the protein causes a sharp drop in the conduction through the
      membrane. 

PMID- 23980183
TI  - Comparative genomics boosts target prediction for bacterial small RNAs.
AB  - Small RNAs (sRNAs) constitute a large and heterogeneous class of bacterial gene
      expression regulators. Much like eukaryotic microRNAs, these sRNAs typically
      target multiple mRNAs through short seed pairing, thereby acting as global
      posttranscriptional regulators. In some bacteria, evidence for hundreds to
      possibly more than 1,000 different sRNAs has been obtained by transcriptome
      sequencing. However, the experimental identification of possible targets and,
      therefore, their confirmation as functional regulators of gene expression has
      remained laborious. Here, we present a strategy that integrates phylogenetic
      information to predict sRNA targets at the genomic scale and reconstructs
      regulatory networks upon functional enrichment and network analysis (CopraRNA,
      for Comparative Prediction Algorithm for sRNA Targets). Furthermore, CopraRNA
      precisely predicts the sRNA domains for target recognition and interaction. When
      applied to several model sRNAs, CopraRNA revealed additional targets and
      functions for the sRNAs CyaR, FnrS, RybB, RyhB, SgrS, and Spot42. Moreover, the
      mRNAs gdhA, lrp, marA, nagZ, ptsI, sdhA, and yobF-cspC were suggested as
      regulatory hubs targeted by up to seven different sRNAs. The verification of many
      previously undetected targets by CopraRNA, even for extensively investigated
      sRNAs, demonstrates its advantages and shows that CopraRNA-based analyses can
      compete with experimental target prediction approaches. A Web interface allows
      high-confidence target prediction and efficient classification of bacterial
      sRNAs. 

PMID- 23980185
TI  - Brown and Goldstein: the cholesterol chronicles.

PMID- 23980186
TI  - In vitro affinity screening of protein and peptide binders by megavalent bead
      surface display.
AB  - The advent of protein display systems has provided access to tailor-made protein
      binders by directed evolution. We introduce a new in vitro display system, bead
      surface display (BeSD), in which a gene is mounted on a bead via strong non
      covalent (streptavidin/biotin) interactions and the corresponding protein is
      displayed via a covalent thioether bond on the DNA. In contrast to previous
      monovalent or low-copy bead display systems, multiple copies of the DNA and the
      protein or peptide of interest are displayed in defined quantities (up to 10(6)
      of each), so that flow cytometry can be used to obtain a measure of binding
      affinity. The utility of the BeSD in directed evolution is validated by library
      selections of randomized peptide sequences for binding to the anti-hemagglutinin
      (HA) antibody that proceed with enrichments in excess of 10(3) and lead to the
      isolation of high-affinity HA-tags within one round of flow cytometric screening.
      On-bead K(d) measurements suggest that the selected tags have affinities in the
      low nanomolar range. In contrast to other display systems (such as ribosome, mRNA
      and phage display) that are limited to affinity panning selections, BeSD
      possesses the ability to screen and rank binders by their affinity in vitro, a
      feature that hitherto has been exclusive to in vivo multivalent cell display
      systems (such as yeast display).

PMID- 23980187
TI  - Remembering Donna Diers.